PMID- 21167949
TI  - The mitochondrial genome of Bacillus stick insects (Phasmatodea) and the
      phylogeny of orthopteroid insects.
AB  - The Order Phasmatodea (stick and leaf insects) includes many well-known species
      of cryptic phytophagous insects. In this work, we sequenced the almost complete
      mitochondrial genomes of two stick insect species of the genus Bacillus.
      Phasmatodea pertain to the Polyneoptera, and represent one of the major clades of
      heterometabolous insects. Orthopteroid insect lineages arose through rapid
      evolutionary radiation events, which likely blurred the phylogenetic
      reconstructions obtained so far; we therefore performed a phylogenetic analysis
      to resolve and date all major splits of orthopteroid phylogeny, including the
      relationships between Phasmatodea and other polyneopterans. We explored several
      molecular models, with special reference to data partitioning, to correctly
      detect any phylogenetic signal lying in rough data. Phylogenetic Informativeness
      analysis showed that the maximum resolving power on the orthopteroid mtDNA
      dataset is expected for the Upper Cretaceous, about 80millionyears ago (Mya), but
      at least 70% of the maximum informativeness is also expected for the 150-200 Mya
      timespan, which makes mtDNA a suitable marker to study orthopteroid splits. A
      complete chronological calibration has also been computed following a Penalized
      Likelihood method. In summary, our analysis confirmed the monophyly of
      Phasmatodea, Dictyoptera and Orthoptera, and retrieved Mantophasmatodea as sister
      group of Phasmatodea. The origin of orthopteroid insects was also estimated to be
      in the Middle Triassic, while the order Phasmatodea seems to appear in the Upper
      Jurassic. The obtained results evidenced that mtDNA is a suitable marker to
      unravel the ancient splits leading to the orthopteroid orders, given a proper
      methodological approach.

PMID- 21167950
TI  - Hippocampal tauopathy in tau transgenic mice coincides with impaired hippocampus
      dependent learning and memory, and attenuated late-phase long-term depression of
      synaptic transmission.
AB  - We evaluated various forms of hippocampus-dependent learning and memory, and
      hippocampal synaptic plasticity in THY-Tau22 transgenic mice, a murine tauopathy
      model that expresses double-mutated 4-repeat human tau, and shows
      neuropathological tau hyperphosphorylation and aggregation throughout the brain.
      Focussing on hippocampus, immunohistochemical studies in aged THY-Tau22 mice
      revealed prominent hyper- and abnormal phosphorylation of tau in CA1 region, and
      an increase in glial fibrillary acidic protein (GFAP) in hippocampus, but without
      signs of neuronal loss. These mice displayed spatial, social, and contextual
      learning and memory defects that could not be reduced to subtle neuromotor
      disability. The behavioral defects coincided with changes in hippocampal synaptic
      functioning and plasticity as measured in paired-pulse and novel long-term
      depression protocols. These results indicate that hippocampal tauopathy without
      neuronal cell loss can impair neural and behavioral plasticity, and further show
      that transgenic mice, such as the THY-Tau22 strain, might be useful for
      preclinical research on tauopathy pathogenesis and possible treatment.

PMID- 21167951
TI  - Fecal lactoferrin and Clostridium spp. in stools of autistic children.
AB  - Stools from autistic and healthy children were studied for fecal lactoferrin,
      Clostridium difficile toxins, Clostridium perfringens enterotoxin and cultured
      for Clostridium spp. Elevated level of FLA was demonstrated in 24.4% stools, all
      from boys (31.25%). No toxins were detected. Clostridium spp. was isolated with
      similar frequency from all samples. C. perfringens were isolated significantly
      often from the autistic stools, intermediate sensitive strains to penicillin 19%,
      to clindamycin 11.3%, and to metronidazole 7.5% were detected. Further studies on
      fecal microflora and inflammatory mediators, with larger groups of patients, are
      required in order to explain their role in neurological deficits.

PMID- 21167952
TI  - Nitric oxide (NO) is associated with gentamicin (GENTA) nephrotoxicity and the
      renal function recovery after suspension of GENTA treatment in rats.
AB  - GENTA nephrotoxicity is likely to be caused, among other factors, by an increase
      of vasoconstrictors or a decrease of vasodilators such as NO. Few days after
      discontinuing GENTA treatment, the renal function is recovered, but if risk
      factors like advanced age, previous renal dysfunction, simultaneous use of other
      nephrotoxic drugs or dehydration are present, severe and progressive renal
      disease occurs. The aim of this study was to evaluate the renal function in rats
      during GENTA treatment and after its suspension as well as its relationship with
      NO. Rats were treated with water (vehicle, CTL) or GENTA (100 mg/kg BW)
      intraperitonially during 10 days; both n=24. Twelve animals of each group were
      sacrificed after blood and 24 h urine were collected, and their kidneys were
      removed for histology. In another rats this procedure underwent after 20 or 30
      days of GENTA suspension. GENTA treated group developed a marked decrease in
      renal function, characterized by an increased serum urea and decreased creatinine
      clearance; NO was increased in the serum and decreased in the urine; all P < 0.01
      vs CTL. Acute tubular necrosis was confirmed in GENTA treated group. After GENTA
      suspension we observed a normalization of urea, creatinine clearance and serum
      and urinary NO; the histological lesions were also attenuated. We suggest that NO
      could play a role in GENTA induced nephrotoxicity and recovery. The understanding
      of this physiopathology could be an useful tool to prevent or blunt the
      nephrotoxicity progression, mainly when risk factors are present.

PMID- 21167953
TI  - Diurnal expression patterns of neurohypophysial hormone genes in the brain of the
      threespot wrasse Halichoeres trimaculatus.
AB  - The aim of this study was to determine the involvement of neurohypophysial
      hormones in the diurnal patterns of the threespot wrasse Halichoeres
      trimaculatus, which is common in coral reefs and exhibits daily behavioral
      periodicity. Prohormone cDNAs of the neurohypophysial peptides, arginine
      vasotocin (AVT) and isotocin (IT), were cloned by 3'- and 5'-rapid amplification
      of cDNA ends (RACE). The distribution and expression patterns of pro-AVT and -IT
      mRNAs in the brain were determined using reverse-transcription polymerase chain
      reaction (RT-PCR) and real-time quantitative PCR, respectively. The respective
      full-length cDNAs of pro-AVT and -IT were 945 and 755 bp in length, respectively.
      The deduced amino acid sequences for pro-AVT and pro-IT were 154 and 156 residues
      in length, respectively. Both pro-peptides contained a signal sequence followed
      by the respective hormones and neurophysin connected by a Gly-Lys-Arg bridge. Pro
      AVT mRNA was detected only in the hypothalamus area, while pro-IT mRNA in the
      whole part of the brain. The relative abundance of pro-AVT and -IT mRNA varied
      according to time of day; it was significantly greater at 12:00 h than at 24:00
      h. Following intraperitoneal administration of melatonin, pro-AVT mRNA abundance
      in the brain decreased, while pro-IT mRNA abundance remained unchanged. These
      results demonstrate that daily fluctuations of pro-AVT and pro-IT levels in the
      brain of threespot wrasse are differentially regulated.

PMID- 21167954
TI  - Effect of different diets on proteolytic enzyme activity, trypsinogen gene
      expression and dietary carbon assimilation in Senegalese sole (Solea
      senegalensis) larvae.
AB  - The effect of diet on larval growth, anionic trypsinogen gene expression
      (ssetryp1), and trypsin (EC 3.4.21.4) and chymotrypsin (EC 3.4.21.1) activities
      was assessed in Solea senegalensis. Changes in larval carbon stable isotope
      (delta(13)C) composition were used to estimate carbon assimilation. Diets were
      supplied for 20days to fish held in larval rearing tanks and consisted of live
      rotifers, Artemia sp. nauplii, rotifers followed by Artemia sp., rotifers co-fed
      with inert diet and inert diet alone. Growth was significantly faster in larvae
      fed only Artemia and those fed rotifers and Artemia (k=0.381-0.387day(-1)).
      Trypsin and chymotrypsin activities increased from 3 to 4days after hatching
      (DAH) in all dietary treatments, while ssetryp1 transcripts increased at 4-5 DAH
      only in larvae fed live prey. ssetryp1 gene expression was activated later in
      larvae fed only Artemia and this corresponded with Artemia delta(13)C values
      being reflected in larval tissue. Larval delta(13)C values also indicated greater
      selection and/or assimilation of rotifers in relation to the inert diet. Results
      demonstrate that during early larval development of sole, diet modulates ssetryp1
      gene expression. The rapid and intense response to diets that promoted different
      growth and survival suggests the suitability of this biomarker as a nutritional
      status indicator in early sole larvae.

PMID- 21167955
TI  - Pepsinogens and pepsins from Japanese seabass (Lateolabrax japonicus).
AB  - Three pepsinogens (PG1, PG2, PG3) were highly purified from the stomach of
      Japanese seabass (Lateolabrax japonicus) by ammonium sulfate fractionation, DEAE
      Sephacel anion exchange column chromatography and Sephacryl S-200 gel-filtration.
      Two dimensional polyacrylamide gel electrophoresis (2D-PAGE) analysis revealed
      that the molecular masses of the three PGs were 35, 37, and 34kDa, and their
      isoelectric points were 5.3, 5.1, and 4.7, respectively. Zymography analysis
      showed that the three pepsinogens had different mobilities and enzymatic
      activities under native conditions. Pepsinogens converted into their active form
      pepsins under pH 2.0 by one-step pathway or stepwise pathway. All three pepsins
      were completely inhibited by pepstatin A, a typical aspartic proteinase
      inhibitor. The N-terminal amino acid sequences of the three pepsinogens were
      determined to the 30th, 30th and 28th amino acid residue and those of their
      corresponding active form pepsins were also determined to the 19th, 18th and 20th
      amino acid residue, respectively. All amino acid sequences of Japanese seabass
      PGs revealed high identities to reported fish and mammalian pepsinogens. The
      effective digestion of fish and shrimp muscular proteins by pepsins indicated
      their physiological function in the degradation of food proteins.

PMID- 21167956
TI  - IGF and GH mRNA levels are suppressed upon exposure to micromolar concentrations
      of cobalt and zinc in rainbow trout white muscle.
AB  - The objective of this study was to assess the effects of cobalt and zinc exposure
      of rainbow trout (Oncorhynchus mykiss) on insulin like growth factors (IGF) and
      growth hormone (GH). Mature rainbow trouts were exposed to 0.42, 2.1, 4.2, 21 and
      42MUmol/L Co(2+) (added as CoCl(2).6H(2)O) and 0.34, 1.7, 3.4, 17 and 34MUmol/L
      Zn(2+) (added as ZnSO(4)i.7H(2)O). After 6, 12, 24 and 48h of treatment,
      expressions of white muscle IGF-I, IGF-II and GH mRNAs were measured by means of
      quantitative Real Time PCR. During the exposure experiments, no mortalities
      occurred. The most effective metal concentrations, which caused significant
      alterations, were determined to be 42MUmol/L Co(2+) (10mg CoCl(2).6H(2)O/L) and
      3.4MUmol/L Zn(+2) (1mg ZnSO(4).7H(2)O/L). The following results were obtained for
      these concentrations. Expression of IGF-I did not change at 6h in zinc treatment
      while the decrease (p<0.05) was observed at 12h and 24h, and this decrease became
      stronger at 48h. Cobalt exposure caused a decrease in IGF-I mRNA level at 6h,
      12h, 24h and 48h (p<0.05). Both zinc and cobalt exposure resulted in significant
      decreases in GH expression at 6h. Exposure of trout to Zn resulted in a decrease
      in expression of IGF-II starting from 6h whereas the significant decrease started
      at 6h in cobalt exposure and this decrease elevated at 24h. The results indicate
      that micromolar cobalt and zinc exposure causes significant attenuation in the
      expressions of these three genes' time dependently. Our findings show that IGF-I
      is the most resistant and GH is the most sensitive component against cobalt and
      zinc exposure. We conclude that IGF/GH axis might be strongly affected by the
      short term exposure to low micromolar concentrations of zinc and cobalt due to
      alterations of these genes.

PMID- 21167957
TI  - Use of Medical Subject Headings (MeSH) in Portuguese for categorizing web-based
      healthcare content.
AB  - INTRODUCTION: Internet users are increasingly using the worldwide web to search
      for information relating to their health. This situation makes it necessary to
      create specialized tools capable of supporting users in their searches.
      OBJECTIVE: To apply and compare strategies that were developed to investigate the
      use of the Portuguese version of Medical Subject Headings (MeSH) for constructing
      an automated classifier for Brazilian Portuguese-language web-based content
      within or outside of the field of healthcare, focusing on the lay public.
      METHODS: 3658 Brazilian web pages were used to train the classifier and 606
      Brazilian web pages were used to validate it. The strategies proposed were
      constructed using content-based vector methods for text classification, such that
      Naive Bayes was used for the task of classifying vector patterns with
      characteristics obtained through the proposed strategies. RESULTS: A strategy
      named InDeCS was developed specifically to adapt MeSH for the problem that was
      put forward. This approach achieved better accuracy for this pattern
      classification task (0.94 sensitivity, specificity and area under the ROC curve).
      CONCLUSIONS: Because of the significant results achieved by InDeCS, this tool has
      been successfully applied to the Brazilian healthcare search portal known as
      Busca Saude. Furthermore, it could be shown that MeSH presents important results
      when used for the task of classifying web-based content focusing on the lay
      public. It was also possible to show from this study that MeSH was able to map
      out mutable non-deterministic characteristics of the web.

PMID- 21167958
TI  - Prostacyclin, not only nitric oxide, is a mediator of the vasorelaxation induced
      by acetylcholine in aortas from rats submitted to cecal ligation and perforation
      (CLP).
AB  - Nitric oxide has been pointed out as the main agent involved in the
      vasodilatation, which is the major symptom of septic shock. However, there must
      be another mediator contributing to the circulatory failure observed in sepsis.
      This study aimed to investigate the endothelium-dependent relaxation induced by
      acetylcholine and the factors involved in this relaxation, using aortic rings
      isolated from rats submitted to cecal ligation and perforation (CLP), 2h after
      induction of sepsis, which characterizes the hyperdynamic phase of sepsis. Under
      inhibition of constitutive NO-synthases (cNOS), the relaxation induced by
      acetylcholine was greater in the aortic rings of rats submitted to CLP compared
      with sham-operated rat aortic rings. The cyclooxygenase inhibitor indomethacin
      normalized this response, and the concentration of the stable metabolite of
      prostacyclin in the aorta of CLP rats increased in basal conditions and after
      stimulation with acetylcholine. Acetylcholine-induced NO production was lower in
      the endothelial cells from the aorta of CLP rats compared with sham rat aorta,
      but the protein expression of the cNOS was not altered. Moreover, iNOS protein
      expression could not be detected. Therefore, prostacyclin, and not only nitric
      oxide, is a mediator of the vasorelaxation induced by acetylcholine in aortas
      from rats submitted to CLP.

PMID- 21167959
TI  - The cardiac neuronal hierarchy and susceptibility to arrhythmias.

PMID- 21167961
TI  - Effects of cyclosporine A and its immunosuppressive or non-immunosuppressive
      derivatives [D-Ser]8-CsA and Cs9 on mitochondria from different brain regions.
AB  - We studied the functional properties of isolated brain mitochondria (BM) prepared
      from total rat brain (BM(total)) or from cerebral subregions under basal and
      Ca(2+) overload conditions in order to evaluate the effects of cyclosporine A
      (CsA) in a regiospecific manner. CsA-induced effects were compared with those of
      two derivatives-the none-immunosuppressive [O-(NH(2)(CH2)(5)NHC(O)CH(2))-D
      Ser](8)-CsA (Cs9) and its congener, the immunosuppressive [D-Ser](8)-CsA. The
      glutamate/malate-dependent state 3 respiration of mitochondria (state 3(glu/mal))
      differed in region-specific manner (cortex > striatum = cerebellum > substantia
      nigra > hippocampus), but was significantly increased by 1MUM CsA (+21+/-5%) in
      all regions. Ca(2+) overload induced by addition of 20MUM Ca(2+) caused a
      significant decrease of state 3(glu/mal) (-45 to -55%) which was almost
      completely prevented in the presence of 1MUM CsA, 1MUM Cs9 or 1MUM [D-Ser](8)
      CsA. Mitochondrial Ca(2+) accumulation thresholds linked to permeability
      transition (PT) as well as the rate and completeness of mitochondrial Ca(2+)
      accumulation differed between different brain regions. For the first time, we
      provide a detailed, regiospecific analysis of Ca(2+)-dependent properties of
      brain mitochondria. Regardless of their immunosuppressive impact, CsA and its
      analogues improved mitochondrial functional properties under control conditions.
      They also preserved brain mitochondria against Ca(2+) overload-mediated PT and
      functional impairments. Since Cs9 does not mediate immunosuppression, it might be
      used as a more specific PT inhibitor than CsA.

PMID- 21167960
TI  - Tissue specific characterisation of Lim-kinase 1 expression during mouse
      embryogenesis.
AB  - The Lim-kinase (LIMK) proteins are important for the regulation of the actin
      cytoskeleton, in particular the control of actin nucleation and depolymerisation
      via regulation of cofilin, and hence may control a large number of processes
      during development, including cell tensegrity, migration, cell cycling, and axon
      guidance. LIMK1/LIMK2 knockouts disrupt spinal cord morphogenesis and synapse
      formation but other tissues and developmental processes that require LIMK are yet
      to be fully determined. To identify tissues and cell-types that may require LIMK,
      we characterised the pattern of LIMK1 protein during mouse embryogenesis. We
      showed that LIMK1 displays an expression pattern that is temporally dynamic and
      tissue-specific. In several tissues LIMK1 is detected in cell-types that also
      express Wilms' tumour protein 1 and that undergo transitions between epithelial
      and mesenchymal states, including the pleura, epicardium, kidney nephrons, and
      gonads. LIMK1 was also found in a subset of cells in the dorsal retina, and in
      mesenchymal cells surrounding the peripheral nerves. This detailed study of the
      spatial and temporal expression of LIMK1 shows that LIMK1 expression is more
      dynamic than previously reported, in particular at sites of tissue-tissue
      interactions guiding multiple developmental processes.

PMID- 21167962
TI  - Hypoxic and hypercapnic challenges unveil respiratory vulnerability of Surf1
      knockout mice, an animal model of Leigh syndrome.
AB  - Surf1 gene mutations were detected as a main cause for Leigh syndrome (LS), also
      known as infantile subacute necrotizing encephalomyelopathy. This syndrome which
      is commonly associated with systemic cytochrome c oxidase (COX) deficiency
      manifests in early childhood and has an invariable poor prognosis. Progressive
      disturbances of the respiratory function, for which both the metabolic condition
      and necrotizing brainstem lesions contribute, belong to the major symptoms of LS.
      A constitutive knockout (KO) mouse for Surf1 enables invasive investigations of
      distinct aspects of LS. In the present study the respiratory function was
      analyzed applying an arterially perfused brainstem preparation. Compared to wild
      type (WT) preparations Surf1 KO preparations had a higher baseline respiratory
      frequency and abnormal responses to hypoxia and hypercapnia that involved both
      respiratory frequency and motor nerve discharge pattern. These data suggest that
      COX deficiency impairs peripheral and/or central chemoreceptor function.

PMID- 21167963
TI  - Respiratory modulation of the pharyngeal airway in lean and obese mice.
AB  - Obesity is an important risk factor for pharyngeal airway collapse in obstructive
      sleep apnea (OSA). To examine the effect of obesity on pharyngeal airway size on
      inspiration and expiration, respiratory-gated MRI of the pharynx was compared in
      New Zealand obese (NZO) and New Zealand white (NZW) mice (weights: 50.4g vs.
      34.7g, p<0.0001). RESULTS: (1) pharyngeal airway cross-sectional area was greater
      during inspiration than expiration in NZO mice, but in NZW mice airway area was
      greater in expiration than inspiration; (2) inspiratory-to-expiratory changes in
      both mouse strains were largest in the caudal pharynx; and (3) during expiration,
      airway size tended to be larger, though non-significantly, in NZW than NZO mice.
      The respiratory pattern differences are likely attributable to obesity that is
      the main difference between NZO and NZW mice. The data support an hypothesis that
      pharyngeal airway patency in obesity is dependent on inspiratory dilation and may
      be vulnerable to loss of neuromuscular pharyngeal activation.

PMID- 21167964
TI  - Characterization of biomodified dentin matrices for potential preventive and
      reparative therapies.
AB  - Biomodification of existing hard tissue structures, specifically tooth dentin, is
      an innovative approach proposed to improve the biomechanical and biochemical
      properties of tissue for potential preventive or reparative therapies. The
      objectives of the study were to systematically characterize dentin matrices
      biomodified by proanthocyanidin-rich grape seed extract (GSE) and glutaraldehyde
      (GD). Changes to the biochemistry and biomechanical properties were assessed by
      several assays to investigate the degree of interaction, biodegradation rates,
      proteoglycan interaction, and effect of collagen fibril orientation and
      environmental conditions on the tensile properties. The highest degree of agent
      dentin interaction was observed with GSE, which exhibited the highest
      denaturation temperature, regardless of the agent concentration. Biodegradation
      rates decreased remarkably following biomodification of dentin matrices after 24h
      collagenase digestion. A significant decrease in the proteoglycan content of GSE
      treated samples was observed using a micro-assay for glycosaminoglycans and
      histological electron microscopy, while no changes were observed for GD and the
      control. The tensile strength properties of GD-biomodified dentin matrices were
      affected by dentin tubule orientation, most likely due to the orientation of the
      collagen fibrils. Higher and/or increased stability of the tensile properties of
      GD- and GSE-treated samples were observed following exposure to collagenase and 8
      months water storage. Biomodification of dentin matrices using chemical agents
      not only affects the collagen biochemistry, but also involves interaction with
      proteoglycans. Tissue biomodifiers interact differently with dentin matrices and
      may provide the tissue with enhanced preventive and restorative/reparative
      abilities.

PMID- 21167965
TI  - Evaluation of photodynamic therapy (PDT) procedures using microfluidic system.
AB  - A hybrid PDMS/glass microfluidic system for evaluation of the efficiency of
      photodynamic therapy is presented. 5-aminolevulinic acid (ALA) was used as a
      precursor of photosensitizer. The geometry of the microdevice presented in this
      paper enables to test different concentrations of the photosensitizer in a single
      assay. The viability of the A549 cells was determined 24 h after PDT procedure
      (irradiation with light which induced a photosensitizer accumulated in carcinoma
      cells, lambda=625 nm). The presented results confirmed the possibility to perform
      the photodynamic therapy process in vitro in microscale and the possibility to
      assess its effectiveness. Moreover, because two identical microstructures on a
      single chip were performed, the microchip can be used for examination
      simultaneously various cell lines (carcinoma and normal) or various
      photosensitizers.

PMID- 21167966
TI  - Synthetic membranes (vesicles) in inorganic ion analysis: a review.
AB  - Vesicles are structures of amphiphile molecules occurring through a self
      aggregation process at the molecular or nano scale level with a large structural
      variety and diverse properties providing a reaction environment for chemical
      reactions that resembles that of natural systems. Their high versatility and
      recognized utility in various applications have triggered a interdisciplinary
      scientific endeavor over their formation, characterization and potential
      applications with impressive results. However, in the vastness of applications
      surrounding vesicular structures, their utility in analytical chemistry has only
      received minor attention. Notwithstanding, studies demonstrating their potential
      as colorimetric or fluorescence sensors, extraction solvents of inorganic ions or
      their chelates and stationary phase modifiers in liquid chromatography have
      appeared. To this end, this article aims to present for the first time the
      analytical chemistry aspects behind the use of vesicle media with special
      emphasis on the detection and determination of inorganic ions and encourage
      further research on this promising field of analytical science.

PMID- 21167967
TI  - Analysis of time-dependent conjugation of gold nanoparticles with an
      antiparkinsonian molecule by using curve resolution methods.
AB  - In this work, the time-dependent conjugation process between a thiolated molecule
      (with anti-parkinsonian properties) and gold nanoparticles has been monitored and
      studied by the combined use of fast acquisition Ultra Violet-Visible (UV-Vis)
      spectra and the ability of Multivariate Curve Resolution-Alternating Least
      Squares (MCR-ALS) technique. From the highly informative kinetic profiles
      obtained it was possible to extract quantitative and qualitative information of
      the conjugation process which includes i) time-dependent concentration profiles
      and pure spectra of species involved on conjugation process, ii) estimation of
      molecule concentration necessary for the completeness of the conjugation
      reaction, iii) molecule footprint and iv) free energy of molecule adsorption.

PMID- 21167968
TI  - Spectrophotometric study of complex formation equilibria in the presence of
      interference using hard-soft net analyte signal method: application to drug-metal
      complexation.
AB  - In this article, the ability of a new and efficient hard-soft method, previously
      proposed by our research group, is reported for modeling of the complex formation
      equilibria in the presence of interferences. This method is based on the net
      analyte signal (NAS) concept, which is a part of total signal that is directly
      related to the concentration of the component of interest. It monitors the
      concentration changes of any chemical species involved in the evolutionary
      process without requiring any pure spectra or having previous knowledge about the
      presence of the interferences. The proposed hard-soft method based on net analyte
      signal (HS-NAS) only needs a chemical model for one of the species involved in
      the reaction under study. The reliability of the method was examined by applying
      it to the measured data and spectrum of the known real systems of Fe(2+)
      azithromycin and Ca(2+)-tetracycline.

PMID- 21167969
TI  - Electrochemical detection of ultratrace nitroaromatic explosives using ordered
      mesoporous carbon.
AB  - A sensitive electrochemical sensor has been fabricated to detect ultratrace
      nitroaromatic explosives using ordered mesoporous carbon (OMC). OMC was
      synthesized and characterized by scanning electron microscopy, transmission
      electron microscopy and nitrogen adsorption/desorption measurements. Glassy
      carbon electrodes functionalized with OMC show high sensitivity of 62.7 MUA cm(
      2) per ppb towards 2,4,6-trinitrotoluene (TNT). By comparison with other
      materials such as carbon nanotubes and ordered mesoporous silica, it is found
      that the high performance of OMC toward sensing TNT is attributed to its large
      specific surface area and fast electron transfer capability. As low as 0.2 ppb
      TNT, 1 ppb 2,4-dinitrotoluene and 1 ppb 1,3-dinitrobenzene can be detected on OMC
      based electrodes. This work renders new opportunities to detect ultratrace
      explosives for applications of environment protections and home securities
      against chemical warfare agents.

PMID- 21167970
TI  - Multicomponent analysis of drinking water by a voltammetric electronic tongue.
AB  - A voltammetric electronic tongue is described that was used for multicomponent
      analysis of drinking water. Measurements were performed on drinking water from a
      tap and injections of the compounds NaCl, NaN(3), NaHSO(3), ascorbic acid, NaOCl
      and yeast suspensions could be identified by use of principal component analysis
      (PCA). A model based on partial least square (PLS) was developed for the
      simultaneously prediction of identification and concentration of the compounds
      NaCl, NaHSO(3) and NaOCl. By utilizing this type of non-selective sensor
      technique for water quality surveillance, it will be feasible to detect a
      plurality of events without the need of a specific sensor for each type of event.

PMID- 21167971
TI  - Synthesis and study of a molecularly imprinted polymer for the specific
      extraction of indole alkaloids from Catharanthus roseus extracts.
AB  - Two molecularly imprinted polymers (MIP) for catharanthine and vindoline have
      been synthesized in order to specifically extract these natural indole alkaloids
      from Catharanthus roseus by solid-phase extraction (SPE). Each MIP was prepared
      by thermal polymerisation using catharanthine (or vindoline) as template,
      methacrylic acid (or itaconic acid) as functional monomer, ethylene glycol
      dimethacrylate (EDMA) as cross-linking agent and acetonitrile (or acetone) as
      porogenic solvent. For catharanthine-MIP, a SPE protocol (ACN-AcOH 99/1 washing
      and MeOH-AcOH 90/10 elution) allows a good MIP/NIP selectivity (imprinting factor
      12.6). The specificity of catharanthine-MIP versus related bisindole alkaloids
      was assessed by cross-reactivity study. The catharanthine-MIP specifically
      retained catharanthine and its N-oxide analogue but displayed a weak cross
      reactivity for other Vinca alkaloids (vinorelbine, vincristine, vinblastine,
      vindoline, vinflunine). It appears that the catharanthine-like unit of these
      molecules are hardly trapped in catharanthine cavities located in the MIP,
      probably due to the sterical hindrance of the vindoline moiety. Finally, the MIP
      SPE applied to C. roseus extract enabled quantitative recovery of catharanthine
      (101%) and the total removal of vindoline. Its capacity was determined and was
      equal to 2.43 MUmol g(-1). Vindoline is a weaker base than catharanthine, so the
      vindoline-MIP was achieved with a strong acidic monomer (itaconic acid) to
      increase vindoline-monomer interactions and a modified washing solvent (ACN-HCOOH
      99/1) to reduce non-specific interactions. The influence of the amount of HCOOH
      (protic modifier) percolated during the washing step upon the elution yield and
      the imprinting factor for vindoline was investigated. This preliminary
      optimisation of the washing step, and in particular the number of moles of acid
      percolated, seems useful to emphasize the use of MIP in conditions of high
      selectivity or high yield. A compromise was obtained with an imprinting factor
      equal to 7.6 and an elution recovery of 33%. However MIP-vindoline failed to
      achieve a specific extraction of vindoline since catharanthine was also extracted
      probably because of strong non-specific interactions occurring between
      catharanthine and the sorbent.

PMID- 21167972
TI  - Self-doped polyaniline as new polyaniline substitute for solid-phase
      microextraction.
AB  - This work is a first study on extraction efficiency and thermal stability of nano
      structured self-doped polyaniline (SPAN) as a coating of solid-phase
      microextraction (SPME) fibers. SPAN-based fibers were prepared using
      electrochemical deposition on platinum wires. The particle sizes of prepared nano
      structure were in the range of 50-100 nm. Extraction properties of the fiber to
      1,4-dioxane were examined using headspace solid-phase microextraction (HS-SPME)
      coupled to gas chromatography-flame ionization detection (GC-FID). The results
      have proved higher thermal stability of the proposed fiber compared to common
      PANI fiber. The SPAN coating was proved to be very stable at relatively high
      temperatures (up to 350  degrees C) with high extraction capacity and long
      lifespan (more than 50 times). Therefore, it can be a good substitute of
      polyaniline (PANI) as a SPME coating. The extraction procedure was optimized by
      selecting the appropriate extraction parameters including extraction time,
      extraction temperature, salt concentration, stirring rate and headspace volume.
      Calibration graph was linear in the concentration range of 1-100 ng mL(-1)
      (R(2)>0.993) with detection limit of 0.1 ng mL(-1). Single fiber and fiber-to
      fiber repeatability were lower than 6.0% and 10.4%, respectively. Different water
      samples were analyzed as real samples and good recoveries (98-120%) were
      obtained.

PMID- 21167973
TI  - A novel needle trap sorbent based on carbon nanotube-sol-gel for microextraction
      of polycyclic aromatic hydrocarbons from aquatic media.
AB  - A new type of composite material based on carbon nanotubes (CNTs) and sol-gel
      chemistry was prepared and used as sorbent for needle trap device (NTD). The
      synthesized composite was prepared in a way to disperse CNTs molecules in a sol
      gel polymeric network. CNT/silica composites with different CNT doping levels
      were successfully prepared, and the extraction capability of each composite was
      evaluated. Effects of surfactant and the oxidation duration of CNTs on the
      extraction efficiency of synthesized composites were also investigated. The
      applicability of the synthesized sorbent was examined by developing a method
      based on needle trap extraction (NTE) and gas chromatography mass spectrometry
      detection (GC-MS) for the determination of polycyclic aromatic hydrocarbons
      (PAHs) in aqueous samples. Important parameters influencing the extraction
      process were optimized and an extraction time of 30 min at 50  degrees C and
      sampling flow rate of 2.5 mL min(-1) gave maximum peak area, when NaCl (15%, w/v)
      was added to the aqueous sample. The linearity for acenaphthene, acenaphthylene
      and fluorene was in the concentration range of 0.01-20 ng mL(-1) and for
      naphthalene and anthracene was in the range of 0.1-50 ng mL(-1). Limits of
      detection was 0.001 ng mL(-1), for acenaphthene, acenaphthylene and fluorene, and
      0.01 ng mL(-1), for naphthalene and anthracene using time-scheduled selected ion
      monitoring (SIM) mode, and the RSD% values (n=3) were all below 11.2% at the 1 ng
      mL(-1) level. The developed method was successfully applied to real water samples
      while the relative recovery percentages obtained for the spiked water samples
      were from 73.8 to 113.8%.

PMID- 21167974
TI  - Urine stability and steroid profile: towards a screening index of urine sample
      degradation for anti-doping purpose.
AB  - The presence of microorganisms in urine samples, under favourable conditions of
      storage and transportation, may alter the concentration of steroid hormones, thus
      altering the correct evaluation of the urinary steroid profile in doping control
      analysis. According to the rules of the World Anti-Doping Agency (WADA technical
      document TD2004 EAAS), a testosterone deconjugation higher than 5% and the
      presence of 5alpha-androstane-3,17-dione and 5beta-androstane-3,17-dione in the
      deconjugated fraction, are reliable indicators of urine degradation. The
      determination of these markers would require an additional quantitative analysis
      since the steroids screening analysis, in anti-doping laboratories, is performed
      in the total (free+conjugated) fraction. The aim of this work is therefore to
      establish reliable threshold values for some representative compounds (namely
      5alpha-androstane-3,17-dione and 5beta-androstane-3,17-dione) in the total
      fraction in order to predict directly at the screening stage the potential
      microbial degradation of the urine samples. Preliminary evidence on the most
      suitable degradation indexes has been obtained by measuring the urinary
      concentration of testosterone, epitestosterone, 5alpha-androstane-3,17-dione and
      5beta-androstane-3,17-dione by gas chromatography-mass spectrometric every day
      for 15 days in the deconjugated, glucuronide and total fraction of 10 pools of
      urines from 60 healthy subjects, stored under different pH and temperature
      conditions, and isolating the samples with one or more markers of degradation
      according to the WADA technical document TD2004EAAS. The threshold values for
      5alpha-androstane-3,17-dione and 5beta-androstane-3,17-dione were therefore
      obtained correlating the testosterone deconjugation rate with the urinary
      concentrations of 5alpha-androstane-3,17-dione and 5beta-androstane-3,17-dione in
      the total fraction. The threshold values suggested as indexes of urine
      degradation in the total fraction were: 10 ng mL(-1) for 5alpha-androstane-3,17
      dione and 20 ng mL(-1) for 5beta-androstane-3,17-dione. The validity of this
      approach was confirmed by the analysis of routine samples for more than five
      months (i.e. on a total of more than 4000 urine samples): samples with a
      concentration of total 5alpha-androstane-3,17-dione and 5beta-androstane-3,17
      dione higher than the threshold values showed a percentage of free testosterone
      higher than 5 of its total amount; whereas free testosterone in a percentage
      higher than 5 of its total amount was not detected in urines with a concentration
      of total 5alpha-androstane-3,17-dione and 5beta-androstane-3,17-dione lower than
      the threshold values.

PMID- 21167975
TI  - Analysis of bisphenols in soft drinks by on-line solid phase extraction fast
      liquid chromatography-tandem mass spectrometry.
AB  - In this study, an automated on-line solid-phase extraction coupled to fast liquid
      chromatography-tandem mass spectrometry (on-line SPE fast LC-MS/MS) method was
      developed for the simultaneous analysis of bisphenol A (BPA), bisphenol F (BPF),
      bisphenol E (BPE), bisphenol B (BPB) and bisphenol S (BPS) in canned soft drinks
      without any previous sample treatment. A C18 (12 MUm particle size) loading
      column was used for the SPE on-line preconcentration before the liquid
      chromatography baseline separation of bisphenol compounds using a C18 Fused
      CoreTM (50 mm * 2.1 mm i.d.) column, which took less than 3 min. Gradient elution
      and heated electrospray were used to reduce matrix effect and improve ionization
      efficiency. To select the most intense and selective transitions, fragmentation
      studies were performed by multiple-stage mass spectrometry in an ion trap mass
      analyzer and tandem mass spectrometry in a triple quadrupole instrument, this
      latter instrument being used for quantitation in SRM mode. Quality parameters of
      the method were established and we obtained a simple, fast, reproducible (RSD
      values lower than 10%) and accurate (precision higher than 93%) method for the
      analysis of bisphenols in canned soft drinks at the ng L(-1) level using matrix
      matched calibration.

PMID- 21167976
TI  - A signal-on electrogenerated chemiluminescent biosensor for lead ion based on
      DNAzyme.
AB  - A highly reproducible and sensitive signal-on electrogenerated chemiluminescence
      (ECL) biosensor based on the DNAzyme for the determination of lead ion was
      developed. The ECL biosensor was fabricated by covalently coupling 5'-amino
      DNAzyme-tagged with ruthenium bis (2,2'-bipyridine) (2,2'-bipyridine-4,4'
      dicarboxylic acid)-ethylenediamine (Ru1-17E') onto the surface of graphite
      electrode modified with 4-aminobenzoic acid, and then a DNA substrate with a
      ribonucleotide adenosine hybridized with Ru1-17E' on the electrode. Upon binding
      of Pb(2+) to the Ru1-17E' to form a complex which catalyzed the cleavage of the
      DNA substrate, the double-stranded DNA was dissociated and thus led to a high ECL
      signal. The signal linearly increases with the concentration of Pb(2+) in the
      range from 5.0 to 80 pM with a detection limit of 1.4 pM and a relative standard
      derivation of 2.3%. This work demonstrates that using DNAzyme tagged with
      ruthenium complex as an ECL probe and covalently coupling method for the
      fabrication of the ECL biosensor with high sensitivity, good stability and
      significant regeneration ability is promising approach.

PMID- 21167977
TI  - High-sensitivity biosensors fabricated by tailoring the localized surface plasmon
      resonance property of core-shell gold nanorods.
AB  - An enhanced sensitive biosensor has been developed to detect biological targets
      by tailoring the localized surface plasmon resonance property of core-shell gold
      nanorods. In this new concept, a shell layer is produced on gold nanorods by
      generating a layer of chalcogenide on the gold nanorod surface after attachment
      of the recognition reagent, namely, goat IgG and antigen of schistosomiasis
      japonica. The bioactivity of these attached biomolecules is retained and the
      sensitivity of this biosensor is thus enhanced significantly. The plasmonic
      properties of the gold nanorods attached with the biomolecules can be adjusted
      and the plasmon resonance wavelength can be red-shifted up to several hundred
      nanometers in the visible or near infrared (NIR) region, which is extremely
      important to biosensing applications. This leads to a lager red-shift in the
      localized surface plasmon resonance absorption compared to the original gold
      nanorod-based sensor and hence offers greatly enhanced sensitivity in the
      detection of schistosomiasis japonica. The human serum infected with
      schistosomiasis japonica diluted to 1:50,000 (volume ratio, serum/buffer
      solution) can be detected readily. The technique offers enhanced sensitivity and
      can be easily extended to other sensing applications based on not only immuno
      recognition but also other types of specific reactions.

PMID- 21167978
TI  - Determination of perfluorinated compounds in fish fillet homogenates: method
      validation and application to fillet homogenates from the Mississippi River.
AB  - We report herein a simple protein precipitation extraction-liquid chromatography
      tandem mass spectrometry (LC/MS/MS) method, validation, and application for the
      analysis of perfluorinated carboxylic acids (C7-C12), perfluorinated sulfonic
      acids (C4, C6, and C8), and perfluorooctane sulfonamide (FOSA) in fish fillet
      tissue. The method combines a rapid homogenization and protein precipitation
      tissue extraction procedure using stable-isotope internal standard (IS)
      calibration. Method validation in bluegill (Lepomis macrochirus) fillet tissue
      evaluated the following: (1) method accuracy and precision in both extracted
      matrix-matched calibration and solvent (unextracted) calibration, (2)
      quantitation of mixed branched and linear isomers of perfluorooctanoate (PFOA)
      and perfluorooctanesulfonate (PFOS) with linear isomer calibration, (3)
      quantitation of low level (ppb) perfluorinated compounds (PFCs) in the presence
      of high level (ppm) PFOS, and (4) specificity from matrix interferences. Both
      calibration techniques produced method accuracy of at least 100+/-13% with a
      precision (%RSD) <=18% for all target analytes. Method accuracy and precision
      results for fillet samples from nine different fish species taken from the
      Mississippi River in 2008 and 2009 are also presented.

PMID- 21167979
TI  - Determination of low levels of cadmium ions by the under potential deposition on
      a self-assembled monolayer on gold electrode.
AB  - The electrochemical determination of low levels of Cd using a self-assembled
      monolayer (SAM) modified Au electrode is reported. Determination was based on the
      stripping of Cd, which was deposited by under potential deposition (UPD). A
      series of short alkanethiol SAMs bearing different end groups, i.e., sulfonate,
      carboxylate and ammonium, were examined. Lowest level of detection (ca. 50 ngL(
      1)) was achieved with a 3-mercaptopropionic acid (MPA) monolayer using
      subtractive anodic square wave voltammetry (SASV). Additional surface methods,
      namely, reductive desorption and X-ray photoelectron spectroscopy, were applied
      to determine the interfacial structure of the electrodeposited Cd on the modified
      electrodes. We conclude that the deposited Cd forms a monoatomic layer, which
      bridges between the gold surface and the alkanethiol monolayer associating with
      both the gold and the sulfur atoms.

PMID- 21167980
TI  - Recent and potential developments in the analysis of urine: a review.
AB  - Analysis of urine is a widely used diagnostic tool that traditionally measured
      one or, at most, a few metabolites. However, the recognition of the need for a
      holistic approach to metabolism led to the application of metabolomics to urine
      for disease diagnostics. This review looks at various aspects of urinalysis
      including sampling and traditional approaches before reviewing recent
      developments using metabolomics. Spectrometric approaches are covered briefly
      since there are already a number of very good reviews on NMR spectroscopy and
      mass spectrometry and other spectrometries are not as highly developed in their
      applications to metabolomics. On the other hand, there has been a recent surge in
      chromatographic applications dedicated to characterising the human urinary
      metabolome. While developments in the analysis of urine encompassing both
      classical approaches of urinalysis and metabolomics are covered, it must be
      emphasized that these approaches are not orthogonal - they both have their uses
      and are complementary. Regardless, the need to normalise analytical data remains
      an important impediment.

PMID- 21167981
TI  - Trends in flow-based analytical methods applied to pesticide detection: a review.
AB  - Recent applications of flow-based analytical methods for pesticide determinations
      are reviewed. This review is focused on the description of electrochemical and
      optical flow sensors, describing the most relevant applications in this field.
      The different approaches employed up to date in electrochemical biosensors,
      together with the possible modifications in the flow methodology and the
      development of multiparameter flow-through optosensors have also been extensively
      described. Advantages, handicaps and current trends of each detection technique
      are critically discussed. The article ends up with a comparison between flow
      based analytical methods and chromatography when applied to pesticide
      determination.

PMID- 21167982
TI  - Sequential automated fusion/extraction chromatography methodology for the
      dissolution of uranium in environmental samples for mass spectrometric
      determination.
AB  - An improved methodology has been developed, based on dissolution by automated
      fusion followed by extraction chromatography for the detection and quantification
      of uranium in environmental matrices by mass spectrometry. A rapid fusion
      protocol (<8 min) was investigated for the complete dissolution of various
      samples. It could be preceded, if required, by an effective ashing procedure
      using the M4 fluxer and a newly designed platinum lid. Complete dissolution of
      the sample was observed and measured using standard reference materials (SRMs)
      and experimental data show no evidence of cross-contamination of crucibles when
      LiBO(2)/LiBr melts were used. The use of a M4 fusion unit also improved
      repeatability in sample preparation over muffle furnace fusion. Instrumental
      issues originating from the presence of high salt concentrations in the digestate
      after lithium metaborate fusion was also mitigated using an extraction
      chromatography (EXC) protocol aimed at removing lithium and interfering matrix
      constituants prior to the elution of uranium. The sequential methodology, which
      can be performed simultaneously on three samples, requires less than 20 min per
      sample for fusion and separation. It was successfully coupled to inductively
      coupled plasma mass spectrometry (ICP-MS) achieving detection limits below 100 pg
      kg(-1) for 5-300 mg of sample.

PMID- 21167983
TI  - Quantitative depth profile analysis of metallic coatings by pulsed radiofrequency
      glow discharge optical emission spectrometry.
AB  - In recent years particular effort is being devoted towards the development of
      pulsed GDs because this powering operation mode could offer important analytical
      advantages. However, the capabilities of radiofrequency (rf) powered glow
      discharge (GD) in pulsed mode coupled to optical emission spectrometry (OES) for
      real depth profile quantification has not been demonstrated yet. Therefore, the
      first part of this work is focussed on assessing the expected advantages of the
      pulsed GD mode, in comparison with its continuous mode counterpart, in terms of
      analytical emission intensities and emission yield parameters. Then, the
      capability of pulsed rf-GD-OES for determination of thickness and compositional
      depth profiles is demonstrated by resorting to a simple multi-matrix calibration
      procedure. A rf forward power of 50 W, a pressure of 600 Pa, 1000 Hz pulse
      frequency and 50% duty cycle were selected. The quantification procedure used was
      validated by analysing conductive layers of thicknesses ranging from a few tens
      of nanometer up to about 20 MUm and varied compositions (hot-dipped zinc,
      galvanneal, back contact of thin film photovoltaic solar cells and tinplates).

PMID- 21167984
TI  - Separation of trace amount of silver using dispersive liquid-liquid based on
      solidification of floating organic drop microextraction.
AB  - In the present work, dispersive liquid-liquid microextraction based on
      solidification of floating organic drop was developed as a simple and rapid
      technique for separation of silver ions from aqueous samples. In this technique,
      700 MUL 0.02% of 5-(4'-dimethylamino benzyliden)-rhodanine (chelating agent) was
      added into the 10 mL analyte sample in a test tube and 30.0 MUL 1-undecanol
      (extraction solvent) was injected shortly thereafter. The test tubes were
      sonicated, centrifuged and then some effective parameters on extraction and
      complex formation, such as type and volume of extraction and disperser solvent,
      pH, the amount of chelating agent and extraction time were optimized. The effect
      of the interfering ions on the analytes recovery was also investigated. The
      calibration graph was linear in the range of 0.10-10.0 ng mL(-1) with detection
      limit of 0.056 ng mL(-1) (n=8). The relative standard deviation (RSD) was +/-4.3%
      (n=8, C=5.0 ng mL(-1)) and the enrichment factor was 250.0. The proposed method
      was applied for extraction and determination of silver in different water
      samples.

PMID- 21167985
TI  - Fully automated determination of parabens, triclosan and methyl triclosan in
      wastewater by microextraction by packed sorbents and gas chromatography-mass
      spectrometry.
AB  - A fully automated method for the determination of triclosan (TCS), its derivative
      methyl triclosan (MeTCS) and six parabens (esters of 4-hydroxybenzoic acid)
      including branched and linear isomers of propyl (i-PrP and n-PrP) and butyl
      paraben (i-BuP and n-BuP) in sewage water samples is presented. The procedure
      includes analytes enrichment by microextraction by packed sorbent (MEPS) coupled
      at-line to large volume injection-gas chromatography-mass spectrometry (LVI-GC
      MS). Under optimised conditions, compounds were extracted from 2 mL samples,
      adjusted at pH 3, using a C18 MEPS-sorbent. Adsorbed analytes were eluted
      directly into the Programmable Temperature Vaporizer (PTV) injector of the
      chromatograph with 2*25 MUL of ethyl acetate. They were quantified using standard
      solutions in ultrapure water submitted to the same sample enrichment process as
      real sewage water samples. After signal normalisation using isotopic labelled
      species as internal surrogates, no differences were noticed among the extraction
      efficiency for sewage and ultrapure water; moreover, the proposed method reported
      lineal calibration curves from 0.1 to 10 ng mL(-1), relative standard deviations
      (%RSD) between 2 and 7.1% and limits of detection (LODs) varying from 0.001 to
      0.015 ng mL(-1) in ultrapure water and from 0.02 to 0.59 ng mL(-1) in the most
      complex sample (raw wastewater).

PMID- 21167986
TI  - Headspace-solid phase microextraction of selenium(IV) from human blood and water
      samples using polypyrrole film and analysis with ion mobility spectrometry.
AB  - Headspace-solid phase microextraction (HS-SPME) with a polypyrrole (PPy)-coated
      fiber was applied as a sample preparation method for determination of selenite
      [Se(IV)] following derivatization with 1,2-diaminobenzene to convert into the
      piaselenol form and analysis by ion mobility spectrometry (IMS). The HS-SPME-IMS
      method presents good repeatability (RSDs <6%), simplicity, good sensitivity and
      short analysis times. The influence of the various analytical parameters on
      microextraction procedure, i.e. ligand concentration, pH, ionic strength,
      equilibrium time and temperature has been evaluated and optimized. The
      calibration graph was linear in the range of 20-320 ng mL(-1) with a detection
      limit of 12 ng mL(-1). The method was applied for determination of selenium in
      human serum and environmental surface water samples with satisfactory recovery.

PMID- 21167987
TI  - Synthesis and evaluation of tetracycline imprinted xerogels: comparison of
      experiment and computational modeling.
AB  - A series of silica-based tetracycline (TC)-imprinted xerogel sorbents were
      prepared by sol-gel processing and were characterized for TC binding. Molecularly
      imprinted xerogels (MIXs) formed from allyltriethoxysilane (AtEOS) and
      tetraethoxysilane (TEOS) and end capped with trimethylchlorosilane exhibited the
      best analytical performance (imprinting factor, IF, of 7.46+/-0.13).
      Computational modeling was used to estimate the interaction energy (IE) between
      TC and each type of silane to evaluate our ability to predict the analytical
      performance of a given MIX. Rankings from the computations agreed with the
      experimental data showing the AtEOS having the highest IE in comparison to the
      other formulations. Together, these results demonstrate the potential and
      limitations of using theoretical calculations to guide the development of analyte
      selective MIXs in comparison to arbitrary trial and error approaches
      traditionally used to produce MIXs as sorbents for solid phase extraction.

PMID- 21167988
TI  - Collection of in vivo-like liver cell secretome with alternative sample
      enrichment method using a hollow fiber bioreactor culture system combined with
      tangential flow filtration for secretomics analysis.
AB  - A hollow fiber bioreactor (HFB) culture system coupled with a tangential flow
      filtration (TFF) device was used for HepG2 cell secretome analysis. In order to
      reduce the loss of low-molecular-weight proteins, two new features, the hollow
      fiber with 0.1 MUm pore size and a TFF device with a membrane of 1kDa molecular
      weight cutoff, were added to the system described previously. The HFB culture
      system and the conventional dish culture method for secretome collection were
      compared side by side. It was observed that only a small fraction of cells
      (<0.01%) were lysed in the HFB culture system, in contrast to the 2.73% in the
      conventional dish culture. A total of 111 proteins were identified in the
      collected conditioned medium (CM) by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) with this improved collection procedure. Many of these
      proteins reported to be biomarkers for liver-related diseases. About 16% of the
      identified proteins were smaller than 20kDa, demonstrating that the modified
      collection system had the ability to reduce the loss of low-molecular-weight
      proteins, in contrast to our previous collection system. The percentage increase
      of proteins classified as extracellular space or plasma membrane between the
      conventional dish culture and the HFB culture system was 40-60%. We believed that
      in vivo-like culture environments could support liver cells to improve protein
      secretion than conventional dish cultures. We suggest that the combination of the
      HFB culture system, TFF device, and LC-MS/MS analysis, would be an efficient
      procedure for the collection and characterization of in vivo-like cell secretome.

PMID- 21167989
TI  - Modification of major plasma proteins by acrylamide and glycidamide: Preliminary
      screening by nano liquid chromatography with tandem mass spectrometry.
AB  - Environmental and food-borne acrylamide is a suspected carcinogen in humans and
      is associated with several cancer types. Its biological metabolite, glycidamide,
      is also harmful to human health. The presence of acrylamide in the living
      environment makes this toxic chemical an important public health issue.
      Acrylamide and glycidamide bind with proteins to form protein adducts in
      metabolic processes. These metabolic adducts can be considered environmental
      modifications of proteins. This study used a simple proteomic strategy to
      identify acrylamide and glycidamide adducts bound in major plasma proteins. After
      simple sample preparation, new protein modifications by acrylamide and
      glycidamide were identified using nano LC combined with quadruple time-of-flight
      (Q-TOF) mass spectrometry. This method required only 10 MUL of human plasma
      sample for protein modification survey. Hopefully, this strategy can help to
      discover protein-acrylamide (or glycidamide) adducts that are biomarkers of human
      exposure to high-dose acrylamide. These biomarkers may also elucidate the
      metabolic pathways of acrylamide and glycidamide.

PMID- 21167990
TI  - Rapid wide-scope screening of drugs of abuse, prescription drugs with potential
      for abuse and their metabolites in influent and effluent urban wastewater by
      ultrahigh pressure liquid chromatography-quadrupole-time-of-flight-mass
      spectrometry.
AB  - This work illustrates the potential of hybrid quadrupole-time-of-flight mass
      spectrometry (QTOF MS) coupled to ultrahigh pressure liquid chromatography
      (UHPLC) to investigate the presence of drugs of abuse in wastewater. After solid
      phase extraction with Oasis MCX cartridges, seventy-six illicit drugs,
      prescription drugs with potential for abuse, and metabolites were investigated in
      the samples by TOF MS using electrospray interface under positive ionization
      mode, with MS data acquired over an m/z range of 50-1000Da. For 11 compounds,
      reference standards were available, and experimental data (e.g., retention time
      and fragmentation data) could be obtained, facilitating a more confident
      identification. The use of a QTOF instrument enabled the simultaneous application
      of two acquisition functions with different collision energies: a low energy (LE)
      function, where none or poor fragmentation took place, and a high energy (HE)
      function, where fragmentation in the collision cell was promoted. This approach,
      known as MS(E), enabled the simultaneous acquisition of full-spectrum accurate
      mass data of both protonated molecules and fragment ions in a single injection,
      providing relevant information that facilitates the rapid detection and reliable
      identification of these emerging contaminants in the sample matrices analyzed. In
      addition, isomeric compounds, like the opiates, morphine and norcodeine, could be
      discriminated by their specific fragments observed in HE TOF MS spectra, without
      the need of reference standards. UHPLC-QTOF MS was proven to be a powerful and
      efficient technique for rapid wide-scope screening and identification of many
      relevant drugs in complex matrices, such as influent and effluent urban
      wastewater.

PMID- 21167991
TI  - Comparison between triple quadrupole, time of flight and hybrid quadrupole time
      of flight analysers coupled to liquid chromatography for the detection of
      anabolic steroids in doping control analysis.
AB  - Triple quadrupole (QqQ), time of flight (TOF) and quadrupole-time of flight
      (QTOF) analysers have been compared for the detection of anabolic steroids in
      human urine. Ten anabolic steroids were selected as model compounds based on
      their ionization and the presence of endogenous interferences. Both qualitative
      and quantitative analyses were evaluated. QqQ allowed for the detection of all
      analytes at the minimum required performance limit (MRPL) established by the
      World Anti-Doping Agency (between 2 and 10 ng mL(-1) in urine). TOF and QTOF
      approaches were not sensitive enough to detect some of the analytes (3'-hydroxy
      stanozolol or the metabolites of boldenone and formebolone) at the established
      MRPL. Although a suitable accuracy was obtained, the precision was unsatisfactory
      (RSD typically higher than 20%) for quantitative purposes irrespective of the
      analyser used. The methods were applied to 30 real samples declared positives
      either for the misuse of boldenone, stanozolol and/or methandienone. Most of the
      compounds were detected by every technique, however QqQ was necessary for the
      detection of some metabolites in a few samples. Finally, the possibility to
      detect non-target steroids has been explored by the use of TOF and QTOF. The use
      of this approach revealed that the presence of boldenone and its metabolite in
      one sample was due to the intake of androsta-1,4,6-triene-3,17-dione.
      Additionally, the intake of methandienone was confirmed by the post-target
      detection of a long-term metabolite.

PMID- 21167992
TI  - Typing of unknown microorganisms based on quantitative analysis of fatty acids by
      mass spectrometry and hierarchical clustering.
AB  - Rapid identification of unknown microorganisms of clinical and agricultural
      importance is not only critical for accurate diagnosis of infections but also
      essential for appropriate and prompt treatment. We describe here a rapid method
      for microorganisms typing based on quantitative analysis of fatty acids by iFAT
      approach (Isotope-coded Fatty Acid Transmethylation). In this work, lyophilized
      cell lysates were directly mixed with 0.5M NaOH solution in d3-methanol and n
      hexane. After 1 min of ultrasonication, the top n-hexane layer was combined with
      a mixture of standard d0-methanol derived fatty acid methylesters with known
      concentration. Measurement of intensity ratios of d3/d0 labeled fragment ion and
      molecular ion pairs at the corresponding target fatty acids provides a
      quantitative basis for hierarchical clustering. In the resultant dendrogram, the
      Euclidean distance between unknown species and known species quantitatively
      reveals their differences or shared similarities in fatty acid related pathways.
      It is of particular interest to apply this method for typing fungal species
      because fungi has distinguished lipid biosynthetic pathways that have been
      targeted for lots of drugs or fungicides compared with bacteria and animals. The
      proposed method has no dependence on the availability of genome or proteome
      databases. Therefore, it is can be applicable for a broad range of unknown
      microorganisms or mutant species.

PMID- 21167993
TI  - Highly sensitive electrochemiluminescent biosensor for adenosine based on
      structure-switching of aptamer.
AB  - A highly sensitive and selective electrochemiluminescent (ECL) biosensor for the
      determination of adenosine was developed. Single DNA (capture DNA) was
      immobilized on the gold electrode through Au-thiol interaction at first. Another
      DNA modified with tris(2,2'-bipyridyl) ruthenium(II)-doped silica nanoparticles
      (Ru-SNPs) that contained adenosine aptamer was then modified on the electrode
      surface through hybridizing with the capture DNA. In the presence of adenosine,
      adenosine-aptamer complex is produced rather than aptamer-DNA duplex, resulting
      with the dissociation of Ru-SNPs-labeled aptamer from the electrode surface and
      the decrease in the ECL intensity. The decrease of ECL intensity has a direct
      relationship with the logarithm of adenosine concentration in the range of
      1.0*10(-10) to 5.0*10(-6)molL(-1). The detection limit of the proposed method is
      3.0*10(-11)molL(-1). The existence of guanosine, cytidine and uridine has little
      interference with adenosine detection, demonstrating that the developed biosensor
      owns a high selectivity to adenosine. In addition, the developed biosensor also
      demonstrates very good reusability, as after being reused for 30 times, its ECL
      signal still keeps 91% of its original state.

PMID- 21167994
TI  - Selenium speciation analysis at trace level in soils.
AB  - This paper describes the development of an analytical methodology to determine
      speciation of selenium present in soils at trace level (MUg kg(-1)). The
      methodology was based on parallel single extractions and high performance liquid
      chromatography hyphenated to inductively coupled plasma mass spectrometry (HPLC
      ICPMS). Two complementary chromatographic separations were used to confirm Se
      species identity. Different extractants, selected on the basis of sequential
      extraction schemes, were compared. Ultrapure water, 0.1 molL(-1) phosphate buffer
      (KH(2)PO(4)/K(2)HPO(4)) at pH 7 and 0.1 molL(-1) sodium hydroxide extractants
      were finally chosen owing to their efficiency in extracting Se and compatibility
      with Se species stability. These extractants allow also assessing respectively
      water-soluble Se (i.e. the most mobile Se fraction), exchangeable Se (i.e. sorbed
      onto soil component surface) and Se bound to soil organic matter. This
      methodology gives thus information on Se mobility related to its distribution in
      soil with preservation of original Se speciation. Detection limits range from 3
      to 29ng(Se)L(-1) and from 0.1 to 10 MUg(Se)kg(-1), allowing determination of Se
      species concentrations in extracts from soils containing native Se at trace
      level. The methodology was applied to three soils with total Se concentrations
      between 210 and 1560 MUg(Se)kg(-1).

PMID- 21167995
TI  - Screening for antioxidants in complex matrices using high performance liquid
      chromatography with acidic potassium permanganate chemiluminescence detection.
AB  - The use of high performance liquid chromatography with acidic potassium
      permanganate chemiluminescence detection to screen for antioxidants in complex
      plant-derived samples was evaluated in comparison with two conventional post
      column radical scavenging assays (2,2-diphenyl-1-picrylhydrazyl radical (DPPH)
      and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical cation
      (ABTS(+))). In this approach, acidic potassium permanganate can react with
      readily oxidisable compounds (potential antioxidants), post-column, to produce
      chemiluminescence. Using flow injection analysis, experimental parameters that
      afforded the most suitable permanganate chemiluminescence signal for a range of
      known antioxidants were studied in a univariate approach. Optimum conditions were
      found to be: 1*10(-3)M potassium permanganate solution containing 1% (w/v) sodium
      polyphosphates adjusted to pH 2 with sulphuric acid, delivered at a flow rate of
      2.5 mL min(-1) per line. Further investigations showed some differences in
      detection selectivity between HPLC with the optimised post-column permanganate
      chemiluminescence detection and DPPH and ABTS(+) assays towards antioxidant
      standards. However, permanganate chemiluminescence detection was more sensitive.
      Moreover, screening for antioxidants in green tea, cranberry juice and thyme
      using potassium permanganate chemiluminescence offers several advantages over the
      traditional DPPH and ABTS(+) assays, such as faster reagent preparation and
      superior stability; simpler post-column reaction manifold; and greater
      compatibility with fast chromatographic separations using monolithic columns.

PMID- 21167996
TI  - New resin gel for uranium determination by diffusive gradient in thin films
      technique.
AB  - A new resin gel based on Spheron-Oxin((r)) chelating ion-exchanger with anchored
      8-hydroxyquinoline functional groups was tested for application in diffusive
      gradient in thin film technique (DGT) for determination of uranium. Selectivity
      of uranium uptake from model carbonate loaded solutions of natural water was
      studied under laboratory conditions and compared with selectivity of the
      conventional Chelex 100 based resin gel. The affinity of Spheron-Oxin((r))
      functional groups enables determination of the overall uranium concentration in
      water containing carbonates up to the concentration level of 10(2) mg L(-1). The
      effect of uranium binding to the polyacrylamide (APA) and agarose diffusive gels
      (AGE) was also studied. Uranium is probably bound in both gels by a weak
      interaction with traces of acrylic acid groups in the structure of APA gel and
      with pyruvic and sulfonic acid groups in the AGE gel. These sorption effects can
      be eliminated to the negligible level by prolonged deployment of DGT probes or by
      disassembling probes after the 1-2 days post-sampling period that is sufficient
      for release of uranium from diffusive gel and its sorption in resin gel.

PMID- 21167997
TI  - Introduction to the special issue on viral channel forming proteins.

PMID- 21167998
TI  - New considerations of ST segment "elevation" and "depression" and accompanying T
      wave configuration in acute coronary syndromes.

PMID- 21167999
TI  - An unusual presentation of left anterior descending artery occlusion:
      significance of lead aVR and T-wave direction.
AB  - Acute occlusion of the left anterior descending coronary artery (LAD) is
      frequently encountered in acute ST-elevation myocardial infarction. Early
      detection of the clinical entity by the presenting electrocardiogram (ECG) should
      result in immediate aggressive clinical management. Although the typical ECG
      pattern of LAD occlusion is ST elevation, also atypical presentations, like ST
      depression, may occur. We describe a case with an unusual ECG pattern that
      suggested acute anterior myocardial infarction due to LAD occlusion.

PMID- 21168000
TI  - Facilitated reperfusion with prehospital glycoprotein IIb/IIIa inhibition:
      predictors of complete ST-segment resolution before primary percutaneous coronary
      intervention in the On-TIME 2 trial: correlates of reperfusion before primary
      PCI.
AB  - OBJECTIVE: The objective of this study is to evaluate the incidence, predictors,
      and outcome of complete ST-segment resolution (STR) during transportation after
      pretreatment with dual or triple antiplatelet therapy in the Ongoing Tirofiban in
      Myocardial Infarction Evaluation (On-TIME) 2 trial. METHODS: Patients with ST
      segment elevation myocardial infarction were randomized in the ambulance to
      pretreatment with high-dose tirofiban (HDT) or to a control pretreatment (placebo
      or no HDT) on top of 600-mg clopidogrel, 500-mg aspirin, and 5000-IU
      unfractionated heparin. Complete STR was defined as >=70% STR on the
      electrocardiogram obtained before percutaneous coronary intervention (PCI) as
      compared with the inclusion electrocardiogram. RESULTS: Complete STR before PCI
      occurred in 16.8% (n = 188/1121) and more frequently in the HDT group (19.0% vs
      14.6%, P = .05). Independent predictors for complete STR before PCI were younger
      age (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.70-0.96, P = .01 per
      10 year increase), fast diagnosis (OR, 0.97; 95% CI, 0.97-1.0, P = .004 per 15
      minute increase time from symptom onset to diagnosis), longer pretreatment time
      (OR, 1.09; 95% CI, 1.03-1.16, P = .003 per 15-minute increase time start study
      medication to angiography), and randomization to HDT (OR, 1.39; 95% CI, 1.0-1.9,
      P = .05). Complete STR before PCI was associated with very low 30-day (0.5% vs
      2.8%, P = .07) and 1-year (1.1% vs 5.0%, P = .019) mortality. CONCLUSIONS: Dual
      or triple antiplatelet pretreatment in the ambulance results in complete STR
      before PCI in 17% of patients. Fast ST-segment elevation myocardial infarction
      diagnosis, prehospital initiation of pretreatment early after symptom onset, and
      HDT independently predicted STR before PCI. Complete STR is associated with
      improved clinical outcome.

PMID- 21168001
TI  - Grade 3 ischemia on the admission electrocardiogram is associated with severe
      microvascular injury on cardiac magnetic resonance imaging after ST elevation
      myocardial infarction.
AB  - BACKGROUND: Grade 3 ischemia during ST elevation myocardial infarction (STEMI) is
      defined as ST elevation with distortion of the terminal portion of the QRS on
      electrocardiogram (ECG). The aim of this study was to evaluate the effect of
      ischemic grade on cardiac magnetic resonance (CMR) imaging infarct
      characteristics such as infarct size, microvascular obstruction (MVO),
      intramyocardial hemorrhage (IMH), and myocardial salvage. METHODS: Patients with
      STEMI treated with primary percutaneous coronary intervention had a 12-lead ECG
      on presentation for analysis of ischemic grade. Gadolinium-enhanced CMR imaging
      was performed within 7 days to assess infarct size, MVO, IMH, and myocardial
      salvage. RESULTS: Of the 37 patients enrolled in the study, grade 3 ischemia was
      present in 32%. Those with grade 3 ischemia had higher peak troponin I levels (P
      = .013), more MVO (P < .001), more IMH (P < .001), larger infarct size (P =
      .025), and less myocardial salvage (P = .012). Regression analysis found that
      grade 3 ischemia, infarct size, and peak troponin I level were significantly
      associated with MVO and IMH. CONCLUSION: Grade 3 ischemia on the admission ECG
      during STEMI is closely associated with the development of severe microvascular
      damage on CMR imaging.

PMID- 21168002
TI  - What is important is the truth.

PMID- 21168003
TI  - Development of a serial comparison program for conduction defects, acute
      myocardial infarction, and the use of additional leads.
AB  - Serial comparison of electrocardiograms (ECGs) is a useful tool in clinical
      diagnostic ECG and an enhancement to computer ECG analysis. When an analysis
      algorithm is modified, the corresponding serial comparison program needs to be
      updated accordingly. The new Philips diagnostic algorithm increased the number of
      leads in the ECG from the traditional 12 leads to 16, making it possible to
      diagnose right ventricular infarct/injury based on right-sided lead V4R. To keep
      pace with the widespread reperfusion therapy for acute myocardial infarct, the
      serial comparison program was revised to recognize the rapid ECG changes in
      patients with ST-elevation myocardial infarct following successful reperfusion
      therapies. The serial comparison program was also enhanced to split "combined"
      statements in the category of ventricular conduction delay (includes incomplete
      ventricular conduction delay and bundle-branch blocks) and compare each of the
      statements separately.

PMID- 21168004
TI  - Electrocautery interference with intraoperative electrocardiogram mimicking ST
      segment elevation.

PMID- 21168005
TI  - The new universal definition of myocardial infarction criteria improve
      electrocardiographic diagnosis of acute coronary syndrome.
AB  - INTRODUCTION/METHODS: To assess whether revised electrocardiographic (ECG)
      criteria improve emergency department identification of patients with acute
      myocardial infarction (MI) or unstable angina (UA) and predict outcome, we
      studied 120 patients with a nondiagnostic initial ECG by prior criteria.
      Electrocardiograms were read in a blinded fashion months apart with standard and
      then revised criteria, and analyzed by chi(2) and logistic regression analysis.
      RESULTS: In 12 subjects (10%), the initial ECG was now interpreted as diagnostic
      of ischemia. Eleven (92%) had an MI, 1 had UA (8%), and none had a noncardiac
      diagnosis. Ischemic ECG changes were strongly associated with MI or UA (P =
      .003). At 1-year follow-up, ECG changes diagnostic of ischemia were associated
      with a trend toward higher mortality (25% vs 7%, P = .07), but after adjustment
      for clinical factors, ECG changes were not an independent predictor of 1-year
      mortality. CONCLUSIONS: Revision of the ECG criteria for ischemia was associated
      with enhanced diagnostic performance and identified a subset of patients at
      higher risk.

PMID- 21168006
TI  - ST-segment dynamics during reperfusion period and the size of myocardial injury
      in experimental myocardial infarction.
AB  - BACKGROUND: Exacerbation of ST elevation associated with reperfusion has been
      reported in patients with myocardial infarction. However, the cause of the
      "reperfusion peak" and relation of its magnitude to the size of myocardial damage
      has not been explored. The aim of our study was to assess the correlation between
      the ST-dynamics during reperfusion, the myocardium at risk (MaR), and the infarct
      size (IS). METHODS: Infarction was induced in 15 pigs by a 40-minute-long balloon
      inflation in the left anterior descending coronary artery. Tetrofosmin Tc 99m was
      given intravenously after 20 minutes of occlusion, and ex vivo single photon
      emission computed tomography was performed to assess MaR. Maximal ST elevation in
      a single lead and maximal sum of ST deviations in 12 leads were measured before,
      during, and after occlusion from continuous 12-lead electrocardiographic
      monitoring. A gadolinium-based contrast agent was given intravenously 30 minutes
      before explantation of the heart. Final IS was estimated using ex vivo cardiac
      magnetic resonance imaging. RESULTS: All pigs developed an anteroseptal infarct
      with MaR = 42% +/- 9% and IS = 26% +/- 7% of left ventricle. In all pigs,
      reperfusion was accompanied by transitory exacerbation of ST elevation that
      measured 1300 +/- 500 MUV as maximum in a single lead compared with 570 +/- 220
      MUV at the end of occlusion (P < .001). The transitory exacerbation of ST
      elevation exceeded the maximal ST elevation during occlusion (920 +/- 420 MUV, P
      < .05). The ST elevation resolved by the end of the reperfusion period (90 +/- 30
      MUV, P < .001). Exacerbation of ST elevation after reperfusion correlated with
      the final IS (r = 0.64, P = .025 for maximal ST elevation in a single lead and r
      = 0.80, P = .002 for sum of ST deviations) but not with MaR (r = 0.43, P = .17
      for maximal ST elevation in a single lead and r = 0.49, P = .11 for sum of ST
      deviations). The maximal ST elevation in a single lead and the sum of ST
      deviations during occlusion did not correlate with either MaR or final IS.
      CONCLUSION: In the experiment, exacerbation of ST elevation is common during
      restoration of blood flow in the occluded coronary artery. The magnitude of the
      exacerbation of ST elevation after reperfusion in experimentally induced
      myocardial infarction in pigs is associated with infarct size but not with MaR.

PMID- 21168007
TI  - The reperfusion ST-peak in acute myocardial infarction.

PMID- 21168008
TI  - Report of the third International Society for Holter and Noninvasive
      Electrocardiology working group on improved electrocardiographic criteria for
      acute and chronic ischemic heart disease--Lund, Sweden: June 2010.
AB  - The third meeting of the International Society for Holter and Noninvasive
      Electrocardiology working group was convened in Lund, Sweden, in June 2010 to
      consider the key clinical challenge of developing electrocardiographic (ECG)
      criteria for identification of the global subendocardial ischemia that results
      from subtotal occlusion of either the left main coronary artery or its
      equivalent. The participants considered the specific abnormalities typical of
      global subendocardial ischemia on the presenting ECG and outlined further studies
      to establish the optimal quantitative ECG criteria. Subgroups on
      Electrocardiology, Myocardial Imaging, and Coronary Intervention met separately
      to establish priorities on their topic and then joined together in a final
      session of the entire working group. The principles for a retrospective and then
      a prospective study were identified, and a writing group was formed.

PMID- 21168009
TI  - Perinatal diagnosis and management of congenital bronchial stenosis or atresia: 4
      cases.

PMID- 21168010
TI  - The evolution of cardiothoracic critical care.

PMID- 21168011
TI  - Adjustments in cardiorespiratory function after pneumonectomy: results of the
      pneumonectomy project.
AB  - OBJECTIVE: To assess lung function, gas exchange, exercise capacity, and right
      sided heart hemodynamics, including pulmonary artery pressure, in patients long
      term after pneumonectomy. METHODS: Among 523 consecutive patients who underwent
      pneumonectomy for lung cancer between January 1992 and September 2001, 117 were
      alive in 2006 and 100 were included in the study. During a 1-day period, each
      patient had complete medical history, chest radiographs, pulmonary function
      studies, resting arterial blood gas analysis, 6-minute walk test, and Doppler
      echocardiography. RESULTS: Most patients (N = 73) had no or only minimal dyspnea.
      On the basis of predicted values, functional losses in forced expiratory volume
      in 1 second and forced vital capacity were 38% +/- 18% and 31% +/- 24%,
      respectively, and carbon monoxide diffusing capacity decreased by 31% +/- 18%.
      There was a significant correlation between preoperative and postoperative forced
      expiratory volume in 1 second (P < .01), and more hyperinflation was associated
      with better lung function (P < .01 for forced expiratory volume in 1 second). Gas
      exchange was normal at rest (Pao(2) = 88 +/- 10 mm Hg; Paco(2) = 42 +/- 3 mm Hg),
      and exercise tolerance (6-minute walk) was also normal (83% +/- 17% of predicted
      values). Thirty-two patients had some degree of pulmonary hypertension, but in
      most of those cases, it was mild to moderate (mean systolic pressure of 36 +/- 9
      mm Hg) and not associated with significant differences in lung function (P = .57
      for forced expiratory volume in 1 second), gas exchange (P = .08), and exercise
      capacity (P = .66). CONCLUSIONS: These findings indicate that despite worsening
      of lung function by approximately 30% after pneumonectomy, most patients can
      adjust to living with only 1 lung. Pulmonary hypertension is uncommon and in most
      cases only mild to moderate.

PMID- 21168013
TI  - Optimized intrapleural cisplatin chemotherapy with a fibrin carrier after
      extrapleural pneumonectomy: a preclinical study.
AB  - OBJECTIVE: Our objective was to evaluate whether platinum concentrations in chest
      wall tissue and in serum are optimized by intracavitary application of cisplatin
      loaded to a fibrin carrier compared with cisplatin solution in a randomized
      setting of a pig model. METHODS: After left-sided pneumonectomy including
      parietal pleurectomy, pigs were randomly assigned to receive either 90 mg/m(2)
      cisplatin intracavitary solution (n = 6) or to receive 5 mg cisplatin-fibrin (n =
      5) applied on a predefined area of the chest wall. Platinum concentration in
      serum as well as in chest wall tissue was determined at several early time points
      until day 5 after treatment. Platinum levels were measured by inductively coupled
      plasma sector field mass spectrometric detection with a matrix-matched
      calibration procedure. RESULTS: The dose- and surface-corrected (geometric) mean
      concentration of cisplatin in chest wall tissue 2 hours but also at day 5 after
      the application was doubled in animals treated with cisplatin-fibrin compared
      with the animals treated with cisplatin-solution. In serum, the dose- and surface
      corrected exposure toward cisplatin (area under the curve(0-5d)) was
      significantly lower with cisplatin-fibrin than with cisplatin-solution (P <
      .0005). This is also reflected by significantly reduced serum creatinine and urea
      values in the cisplatin-fibrin group (P < .0001). Animals treated with cisplatin
      fibrin additionally had a significantly better postoperative course as assessed
      by a well-being score (P < .001). CONCLUSIONS: After cisplatin-fibrin treatment,
      cisplatin tissue concentration was increased whereas systemic cisplatin
      concentrations were significantly reduced in comparison with cisplatin-solution
      treatment. This finding offers a clear advantage inasmuch as rate and severity of
      systemic adverse events can be reduced while local cytotoxic concentrations are
      at least maintained.

PMID- 21168015
TI  - Outcomes of coronary artery bypass grafting and reduction annuloplasty for
      functional ischemic mitral regurgitation: a prospective multicenter study
      (Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral
      Valve).
AB  - OBJECTIVE: Functional ischemic mitral regurgitation is a complication of
      ventricular remodeling; standard therapy is reduction annuloplasty and coronary
      artery bypass grafting. Unfortunately, outcomes are retrospective and
      contradictory. We report a multicenter study that documents the outcomes of
      reduction annuloplasty for functional ischemic mitral regurgitation. METHODS:
      Twenty-one centers randomized 75 patients to the coronary artery bypass grafting
      + reduction annuloplasty subgroup that was the control arm of the Randomized
      Evaluation of a Surgical Treatment for Off-pump Repair of the Mitral Valve trial.
      Entry criteria included patients requiring revascularization, patients with
      severe or symptomatic moderate functional ischemic mitral regurgitation, an
      ejection fraction 25% or greater, a left ventricular end-diastolic dimension 7.0
      cm or less, and more than 30 days since acute myocardial infarction. All
      echocardiograms were independently scored by a core laboratory. Reduction
      annuloplasty was achieved by device annuloplasty. Two patients underwent
      immediate intraoperative conversion to a valve replacement because reduction
      annuloplasty was unable to correct mitral regurgitation; as-treated results are
      presented. RESULTS: Thirty-day mortality was 4.1% (3/73). Patients received an
      average of 2.8 bypass grafts. Mean follow-up was 24.6 months. Mitral
      regurgitation was reduced from 2.6 +/- 0.8 preoperatively to 0.3 +/- 0.6 at 2
      years. Freedom from death or valve reoperation was 78% +/- 5% at 2 years. There
      was significant improvement in ejection fraction and New York Heart Association
      class with reduction of left ventricular end-diastolic dimension. Cox regression
      analyses suggested that increasing age (P = .001; hazard ratio, 1.16 per year;
      95% confidence interval, 1.06-1.26) and renal disease (P = .018; hazard ratio,
      3.48; 95% confidence interval, 1.25-9.72) were associated with decreased
      survival. CONCLUSIONS: Coronary artery bypass grafting + reduction annuloplasty
      for functional ischemic mitral regurgitation predictably reduces mitral
      regurgitation and relieves symptoms. This treatment of moderate to severe mitral
      regurgitation is associated with improved indices of ventricular function,
      improved New York Heart Association class, and excellent freedom from recurrent
      mitral insufficiency. Although long-term prognosis remains guarded, this
      multicenter study delineates the intermediate-term benefits of such an approach.

PMID- 21168017
TI  - Outcomes for endocarditis surgery in North America: a simplified risk scoring
      system.
AB  - OBJECTIVE: Operation for infective endocarditis is associated with the highest
      mortality of any valve disease, with overall rates of in-hospital mortality
      exceeding 20%. The Society of Thoracic Surgeons Adult Cardiac Surgery Database
      was examined to develop a simple risk scoring system and identify areas for
      quality improvement. METHODS: From 2002 through 2008, 19,543 operations were
      performed for infective endocarditis. Logistic regression analysis related
      baseline characteristics to both operative mortality and a composite of mortality
      and major morbidity within 30 days. Points were assigned to each risk factor, and
      estimated risk was obtained by averaging events for all patients having the same
      number of points. RESULTS: Overall unadjusted mortality was 8.2%, and
      complications occurred in 53%. Significant preoperative risk factors for
      mortality (associated points) were as follows: emergency, salvage status, or
      cardiogenic shock (17), preoperative hemodialysis, renal failure, or creatinine
      level less than 2.0 (12), preoperative inotropic or balloon pump support (10),
      active (vs treated) endocarditis (10), multiple valve involvement (9), insulin
      dependent diabetes (8), arrhythmia (8), previous cardiac surgery (7), urgent
      status without cardiogenic shock (6), non-insulin-dependent diabetes (6),
      hypertension (5), and chronic lung disease (5), with a C statistic of 0.7578 (all
      P < .001). Risk-adjusted mortality and major morbidity were unchanged over the
      course of the study. In the entire data set, mortality was better if "any valve"
      was repaired (odds ratio = 0.76; P = .0023). CONCLUSIONS: Operative mortality for
      surgically treated infective endocarditis is substantially lower than reported in
      hospital mortality rates for infective endocarditis. The described risk scoring
      system will inform clinical decision-making in these complex patients.

PMID- 21168019
TI  - The Cox maze IV procedure: predictors of late recurrence.
AB  - OBJECTIVES: The Cox maze III procedure achieved high cure rates and became the
      surgical gold standard for the treatment of atrial fibrillation. Because of its
      invasiveness, a more simplified ablation-assisted procedure, the Cox maze IV
      procedure, has been performed at our institution since January 2002. The study
      examined multiple preoperative and perioperative variables to determine
      predictors of late recurrence. METHODS: Data were collected prospectively on 282
      patients who underwent the Cox maze IV procedure from January 2002 through
      December 2009. Forty-two percent of patients had paroxysmal and 58% had either
      persistent or long-standing persistent atrial fibrillation. All patients were
      available for follow-up. Follow-up included electrocardiograms in all patients.
      Since 2006, 24-hour Holter monitoring was obtained in 94% of patients at 3, 6,
      and 12 months. Data were analyzed by means of logistic regression analysis at 12
      months, with 13 preoperative and perioperative variables used as covariates.
      RESULTS: Sixty-six percent of patients had a concomitant procedure. After an
      ablation-assisted Cox maze procedure, the freedom from atrial fibrillation was
      89%, 93%, and 89% at 3, 6, and 12 months, respectively. The freedom from both
      atrial fibrillation and antiarrhythmic drugs was 63%, 79%, and 78% at 3, 6, and
      12 months, respectively. The risk factors for atrial fibrillation recurrence at 1
      year were enlarged left atrial diameter (P = .027), failure to isolate the entire
      posterior left atrium (P = .022), and early atrial tachyarrhythmias (P = .010).
      CONCLUSIONS: The Cox maze IV procedure has a high success rate at 1 year, even
      with improved follow-up and stricter definitions of failure. In patients with
      large left atria, there might be a need for more extensive size reduction or
      expanded lesion sets.

PMID- 21168021
TI  - Does early surgical intervention improve left ventricular mass regression after
      mitral valve repair for leaflet prolapse?
AB  - BACKGROUND: Left ventricular hypertrophy is associated with adverse
      cardiovascular outcomes. It is unclear whether hypertrophy caused by severe
      chronic mitral regurgitation regresses after mitral valve repair and, if so,
      which factors promote reverse remodeling and influence its prognostic
      significance. METHODS: Between March 1995 and December 2005, 2589 patients had
      mitral valve repair. Five hundred thirty patients (346 of whom were male)
      underwent isolated repair for leaflet prolapse and had echocardiographic data
      available from which the left ventricular mass index could be calculated.
      Concomitant preoperative tricuspid valve regurgitation was more than mild in 95
      (18%) patients. Those with preoperative atrial fibrillation and other cardiac
      pathologies necessitating intracardiac repair were not included. RESULTS:
      Significant regression of left ventricular mass index occurred during the first 3
      years (-28 g/m(2), P < .001) and was maintained during follow-up for more than 3
      years (-26 g/m(2), P < .001). Higher preoperative left ventricular ejection
      fraction and greater preoperative left ventricular mass index independently
      predicted improved left ventricular mass index regression at 3 years. During
      follow-up of greater than 3 years, greater preoperative left ventricular mass
      index persisted in predicting improved mass regression (P < 0.001), and greater
      than mild preoperative tricuspid valve regurgitation was associated with less
      mass regression (P < .001). Late recovery of normal left ventricular ejection
      fraction was impaired in those with the greatest residual left ventricular mass;
      however, there was no difference in late symptoms or survival. CONCLUSIONS:
      Performing mitral valve repair before a decrease in left ventricular ejection
      fraction and the development of significant secondary tricuspid valve
      regurgitation is associated with a greater likelihood of significant regression
      of left ventricular mass, possibly predicting improved recovery of normal left
      ventricular function after surgical intervention. These data provide additional
      support for early degenerative mitral valve repair.

PMID- 21168023
TI  - Complex coronary anatomy in coronary artery bypass graft surgery: impact of
      complex coronary anatomy in modern bypass surgery? Lessons learned from the
      SYNTAX trial after two years.
AB  - OBJECTIVE: SYNTAX study compares outcomes of coronary artery bypass grafting with
      percutaneous coronary intervention in patients with 3-vessel and/or left main
      disease. Complexity of coronary artery disease was quantified by the SYNTAX
      score, which combines anatomic characteristics of each significant lesion. This
      study aims to clarify whether SYNTAX score affects the outcome of bypass grafting
      as defined by major adverse cerebrovascular and cardiac events (MACCE) and its
      components over a 2-year follow-up period. METHODS: Of the 3075 patients enrolled
      in SYNTAX, 1541 underwent coronary artery bypass grafting (897 randomized
      controlled trial patients, and 644 registry patients). All patients undergoing
      bypass grafting were stratified according to their SYNTAX score into 3 tertiles:
      low (0-22), intermediate (22-32), and high (>=33) complexity. Clinical outcomes
      up to 2 years after allocation were determined for each group and further risk
      factor analysis was performed. RESULTS: Registry patients had more complex
      disease than those in the randomized controlled trial (SYNTAX score: registry
      37.8 +/- 13.3 vs randomized 29.1 +/- 11.4; P < .001). At 30 days, overall
      coronary bypass mortality was 0.9% (registry 0.6% vs randomized 1.2%). MACCE rate
      at 30 days was 4.4% (registry 3.4% vs randomized 5.2%). SYNTAX score did not
      significantly affect overall 2-year MACCE rate of 15.6% for low, 14.3% for
      medium, and 15.4% for high SYNTAX scores. Compared with randomized patients,
      registry patients had a lower rate of overall MACCE rate (registry 13.0% vs
      randomized 16.7%; P = .046) and repeat revascularization (4.7% vs 8.6%; P =
      .003), whereas other event rates were comparable. Risk factor analysis revealed
      left main disease (P = .049) and incomplete revascularization (P = .005) as
      predictive for adverse 2-year outcomes. CONCLUSIONS: The outcome of coronary
      artery bypass grafting was excellent and independent from the SYNTAX score.
      Incomplete revascularization rather than degree of coronary complexity adversely
      affects late outcomes of coronary bypass.

PMID- 21168026
TI  - Simulating video-assisted thoracoscopic lobectomy: a virtual reality cognitive
      task simulation.
AB  - OBJECTIVE: Current video-assisted thoracoscopic surgery training models rely on
      animals or mannequins to teach procedural skills. These approaches lack inherent
      teaching/testing capability and are limited by cost, anatomic variations, and
      single use. In response, we hypothesized that video-assisted thoracoscopic
      surgery right upper lobe resection could be simulated in a virtual reality
      environment with commercial software. METHODS: An anatomy explorer (Maya
      [Autodesk Inc, San Rafael, Calif] models of the chest and hilar structures) and
      simulation engine were adapted. Design goals included freedom of port placement,
      incorporation of well-known anatomic variants, teaching and testing modes, haptic
      feedback for the dissection, ability to perform the anatomic divisions, and a
      portable platform. RESULTS: Preexisting commercial models did not provide
      sufficient surgical detail, and extensive modeling modifications were required.
      Video-assisted thoracoscopic surgery right upper lobe resection simulation is
      initiated with a random vein and artery variation. The trainee proceeds in a
      teaching or testing mode. A knowledge database currently includes 13 anatomic
      identifications and 20 high-yield lung cancer learning points. The "patient" is
      presented in the left lateral decubitus position. After initial camera port
      placement, the endoscopic view is displayed and the thoracoscope is manipulated
      via the haptic device. The thoracoscope port can be relocated; additional ports
      are placed using an external "operating room" view. Unrestricted endoscopic
      exploration of the thorax is allowed. An endo-dissector tool allows for hilar
      dissection, and a virtual stapling device divides structures. The trainee's
      performance is reported. CONCLUSIONS: A virtual reality cognitive task simulation
      can overcome the deficiencies of existing training models. Performance scoring is
      being validated as we assess this simulator for cognitive and technical surgical
      education.

PMID- 21168028
TI  - Attenuation of spinal cord ischemia and reperfusion injury by erythropoietin.
AB  - BACKGROUND: Paraplegia remains a devastating complication for patients undergoing
      thoracic aortic procedures. Although surgical adjuncts have evolved to reduce the
      risk of paraplegia, no pharmacologic therapies have proven efficacious in
      attenuating spinal cord ischemia-reperfusion injury. Effects of erythropoietin in
      spinal cord ischemia-reperfusion injury, however, have not yet been elucidated.
      We hypothesized that pretreatment with erythropoietin would attenuate functional
      and cytoarchitectural spinal cord injury related to high-risk aortic procedures.
      METHODS: Adult male mice were subjected to ischemia-reperfusion. Aortic arch and
      proximal left subclavian arteries were clamped for 5 minutes; animals were
      observed for 48 hours. Neurologic scores of hind limb function were assessed
      every 12 hours. Experimental groups consisted of treatment with erythropoietin 4
      hours before crossclamping (n = 7), ischemic controls (n = 7), and sham ischemia
      (operation without crossclamping, n = 6). Thoracolumbar sections of spinal cord
      were removed after 48 hours and preserved for cytoarchitectural analysis.
      RESULTS: Mice pretreated with erythropoietin exhibited significant preservation
      of hind limb motor function. All mice without pretreatment were paralyzed at 48
      hours. Mice with erythropoietin pretreatment had improved motor function; 3 had
      no measurable neurologic deficit at 48 hours. Histologic analysis in mice treated
      with erythropoietin showed markedly reduced neuronal cell injury. CONCLUSIONS:
      Erythropoeitin preserves both function and histologic appearance in mice
      undergoing spinal cord ischemia-reperfusion. With further elucidation of
      mechanisms of protection and optimal administration, erythropoietin could become
      an important adjunct in reducing the incidence and severity of spinal cord injury
      related to aortic interventions.

PMID- 21168030
TI  - Continued depression of maximal oxygen consumption and mitochondrial proteomic
      expression despite successful coronary artery bypass grafting in a swine model of
      hibernation.
AB  - OBJECTIVE: Clinical studies indicate incomplete functional recovery of
      hibernating myocardium after coronary artery bypass grafting. We hypothesized
      that persistent contractile abnormalities after coronary artery bypass grafting
      are associated with decreased mitochondrial proteins involving electron transport
      chain that might limit maximal oxygen consumption. METHODS: Seven pigs with
      hibernating myocardium underwent off-pump revascularization with left internal
      thoracic artery to mid left anterior descending artery. At 4 weeks, left internal
      thoracic artery anastomosis was patent by multidetector computed tomography.
      Regional function (transthoracic echocardiography) and blood flow (microspheres)
      were assessed at rest and during high-dose dobutamine (40 MUg/[kg . min]).
      Expression of electron transport chain proteins was analyzed with isobaric tags
      for relative and absolute quantification. RESULTS: After revascularization,
      multidetector computed tomography confirmed severe left anterior descending
      stenosis and patent left internal thoracic artery graft. Regional function and
      blood flow normalized at rest; however, function in left anterior descending
      distribution remained depressed relative to remote regions, and myocardial blood
      flow in that region did not increase normally when challenged with high-work
      state. Concomitant with reduced maximal blood flow response in left anterior
      descending region was more than 40% reduction in electron transport chain
      proteins essential to adenosine triphosphate production. CONCLUSIONS: Despite
      successful revascularization of hibernating myocardium, regional function and
      blood flow remained depressed during catecholamine stress. Electron transport
      chain proteins known to be downregulated during adaptive process within
      hibernating myocardium did not normalize after revascularization. These data
      demonstrate a potential bioenergetic cause of persistent dysfunction and heart
      failure within successfully revascularized hibernating myocardium.

PMID- 21168034
TI  - Giant aortic root aneurysm in Marfan syndrome: a rare complication in early
      childhood.

PMID- 21168032
TI  - Cardiac xenotransplantation technology provides materials for improved
      bioprosthetic heart valves.
AB  - OBJECTIVES: Human subjects and Old World primates have high levels of antibody to
      galactose-alpha-1,3 galactose beta-1,4-N-acetylglucosamine (alpha-Gal).
      Commercially available bioprosthetic heart valves of porcine and bovine origin
      retain the Gal antigen despite current processing techniques. Gal-deficient pigs
      eliminate this xenoantigen. This study tests whether binding of human anti-Gal
      antibody effects calcification of wild-type and Gal-deficient glutaraldehyde
      fixed porcine pericardium by using a standard subcutaneous implant model.
      METHODS: Expression of alpha-Gal was characterized by lectin Griffonia
      simplicifolia-IB4 staining. Glutaraldehyde-fixed pericardial disks from Gal
      positive and Gal-deficient pigs were implanted into 12-day-old Wistar rats and
      1.5-kg rabbits with and without prelabeling with affinity-purified human anti-Gal
      antibody. Calcification of the implants was determined after 3 weeks by using
      inductively coupled plasma spectroscopy. RESULTS: The alpha-Gal antigen was
      detected in wild-type but not Gal-deficient porcine pericardium. Wild-type disks
      prelabeled with human anti-Gal antibody exhibited significantly greater
      calcification compared with that seen in antibody-free wild-type samples (mean +/
      standard error of the mean: 111 +/- 8.4 and 74 +/- 9.6 mg/g, respectively; P =
      .01). In the presence of anti-Gal antibody, a significantly greater level of
      calcification was detected in wild-type compared with GTKO porcine pericardium
      (111 +/- 8.4 and 55 +/- 11.8 mg/g, respectively; P = .005). Calcification of Gal
      deficient pericardium was not affected by the presence of anti-Gal antibody (51
      +/- 9.1 and 55 +/- 11.8 mg/g). CONCLUSIONS: In this model anti-Gal antibody
      accelerates calcification of wild-type but not Gal-deficient glutaraldehyde-fixed
      pericardium. This study suggests that preformed anti-Gal antibody present in all
      patients might contribute to calcification of currently used bioprosthetic heart
      valves. Gal-deficient pigs might become the preferred source for new, potentially
      calcium-resistant bioprosthetic heart valves.

PMID- 21168035
TI  - A new technique facilitating intraoperative, high-frequency echocardiography of
      coronary bypass graft anastomoses.

PMID- 21168036
TI  - Difference in outcome in the transection of the pulmonary artery and vein.

PMID- 21168037
TI  - Crunch time for heart failure care in England and Wales.

PMID- 21168038
TI  - New obesity pill: new hopes, old fears.

PMID- 21168039
TI  - Artemisinin resistance--the clock is ticking.

PMID- 21168043
TI  - Ivabradine and outcomes in chronic heart failure.

PMID- 21168044
TI  - Ivabradine and outcomes in chronic heart failure.

PMID- 21168045
TI  - Vertebroplasty versus conservative treatment for vertebral fractures.

PMID- 21168046
TI  - Vertebroplasty versus conservative treatment for vertebral fractures.

PMID- 21168048
TI  - Under-reporting of progressive supranuclear palsy.

PMID- 21168049
TI  - Moral algorithm versus human rights law; philosophy versus ethos.

PMID- 21168050
TI  - A plea for investment in district hospitals.

PMID- 21168051
TI  - Breaking away from the disease-focused paradigm.

PMID- 21168052
TI  - Music of the heart.

PMID- 21168054
TI  - Neuroscience Editorial.

PMID- 21168053
TI  - Cytotoxic therapy for severe swine flu A/H1N1.

PMID- 21168055
TI  - [The role of moxifloxacin in the prophylaxis of post-surgical endophthalmitis].

PMID- 21168056
TI  - [Comparison of Goldmann tonometry, pneumotonometry and the effect of the central
      corneal thickness].
AB  - PURPOSE: To compare the intraocular pressure (IOP) measurements using the
      Goldmann applanation tonometer (GAT) and contact pneumotonometer (NTC), and to
      evaluate the effects of central corneal thickness (CCT) on the readings. METHODS:
      This was a prospective, observational clinical study, which included 96 eyes of
      49 patients, 40 glaucomatous, 29 ocular hypertensive and 27 normal subjects. The
      IOP measurements were performed with each tonometer. The CCT was also measured.
      RESULTS: A strong correlation coefficient between GAT and the NTC was found
      (Pearson=0.922, p<0.001). The mean of paired differences between GAT and NTC was
      0.72 +/- 2.82 mmHg. The mean difference between GAT and NTC was low at lower
      levels of PIO and higher at higher levels of IOP. Readings with the GAT showed a
      mean increase in IOP of 0.47 mmHg for every 10 MUm of CCT, and the NTC 0.34 mmHg
      for every 10 MUm, the diference was not statistically significant. CONCLUSIONS:
      The contact pneumotonometer is a reliable method in diagnosis and follow up of
      our population. The effect of the central corneal thickness was more important
      for the Goldmann applanation tonometer.

PMID- 21168057
TI  - [Morphometric analysis of corneal endothelium after intravitreal ranibizumab
      (Lucentis) in age-related macular degeneration treatment].
AB  - PURPOSE: To determine the effect of intravitreal injection of 0.5mg ranibizumab
      on the corneal endothelium in patients with age-related macular degeneration
      (AMD). METHODS: Observational, prospective case series pilot study. Twenty-six
      eyes of 26 consecutive patients with AMD were evaluated. All participants
      received one monthly intravitreal injections of 0.5mg ranibizumab for three
      consecutive months. The follow-up period was 6 months. Central corneal specular
      microscopy was performed before injection and at 7 days and 6 months after the
      first intravitreal injection. The endothelial cell density, coefficient of
      variation of cell size, and percentage of hexagonal cells were analyzed and the
      central corneal thickness was measured. RESULTS: There were no significant
      differences in the endothelial cell densities, coefficients of variation of cell
      size and percentages of hexagonal cells before injection and at 7 days and 6
      months after the first intravitreal ranibizumab injection (P>0.5). There was also
      no significant difference in central corneal thickness measurements through the
      follow-up period (P>0.5). CONCLUSIONS: Repeated intravitreal injections of 0.5mg
      ranibizumab do not seem to cause substantial changes in the corneal endothelium.

PMID- 21168058
TI  - [Vitrectomy surgery for the treatment of the vitreo-retinal complications of the
      pars planitis].
AB  - OBJECTIVE: To evaluate the effect of pars plana vitrectomy in the management of
      patients with pars planitis. METHODS: A retrospective analysis of the clinical
      course, post-operative complications and recurrent uveal inflammation following
      pars plana vitrectomy in patients with pars planitis. RESULTS: The study included
      22 eyes of 19 patients. The mean follow-up was 55.7 (+/- 39.6) months (range 7 -
      144 months). The surgical indications were, persistent vitreous opacities in 10
      eyes, vitreous haemorrhage in 9 eyes, and epiretinal membrane in 3 eyes. There
      was an improvement in the clinical course of the uveitis in 19 of the 22 eyes
      (86.4%), allowing the suspension of the systemic treatment in 16 patients. An
      improvement of the visual acuity was observed in 20 eyes (90.9%). The most common
      post-operative complications were, lens opacities in 9 eyes (40.9%), and glaucoma
      in 4 eyes (18.2%). CONCLUSIONS: The results of this study suggest that pars plana
      vitrectomy has a beneficial effect on the course and visual function of patients
      with vitreo-retinal complications associated with pars planitis.

PMID- 21168059
TI  - [Treatment with photodynamic therapy of circumscribed choroidal hemangioma].
AB  - CASE REPORTS: The clinical characteristics of three patients with circumscribed
      choroidal haemangioma and subfoveal exudation detected by optical coherence
      tomography are described in this paper. The three patients were successfully
      treated with photodynamic therapy. DISCUSSION: Photodynamic therapy is the most
      adequate therapeutic option for circumscribed choroidal hemangioma associated
      with subfoveal exudation. Some questions such as whether attempts should be made
      to obtain a complete tumour regression, laser settings or the way the spots must
      be applied remain unresolved.

PMID- 21168060
TI  - [Creutzfeldt - Jakob presenting with isolated visual symptoms: the Heidenhain
      variant].
AB  - CLINICAL CASE: We report the case of a 67 year old female complaining of
      decreased vision and diagnosed with the Heidenhain variant of sporadic
      Creutzfeldt-Jakob disease. Her past medical history was unremarkable. She died
      less than three months after the onset. DISCUSSION: The Heidenhain variant of
      sporadic Creutfeld-Jakob disease should be suspected in patients suffering from
      early visual disturbances, unremarkable ophthalmic examination, and subsequent
      rapid decline of their cognitive function. A complete neurological exam including
      electroencephalogram recordings and magnetic resonance is mandatory. These
      patients share a common genotype (PRNP codon 129 MM) associated with a clinically
      typical disease course.

PMID- 21168061
TI  - [The blind men of M'Hammed Issiakhem].

PMID- 21168062
TI  - Special issue on molecular basis of multiple sclerosis.

PMID- 21168064
TI  - Cardiovascular pathology at the crossroads: the dilemma of cardiac pathologists.

PMID- 21168066
TI  - Essential nursing competencies related to HIV and AIDS.
AB  - With nearly 33 million global citizens living with HIV or AIDS, the need for a
      highly qualified, competent nursing workforce is critical. With the recent
      increase in global funding to expand access to antiretroviral therapy, there have
      been considerable efforts to improve the capacity of nurses to initiate and
      maintain antiretroviral therapy while evaluating its effectiveness, monitoring
      for side effects, reducing the incidence of drug-drug interactions (including
      drug interactions related to therapies provided by traditional healers),
      promoting adherence to therapies, and providing management of symptoms.
      Therefore, using a participatory action approach, nursing leaders from six sub
      Saharan African countries collaborated to develop the essential nursing
      competencies related to HIV and AIDS. These competencies can help to guide
      preservice education related to HIV and AIDS, to strengthen in-service or
      capacity-building programs designed for already qualified nurses, and to guide
      policy and regulatory reform in the context of task-shifting, task-sharing, and
      scope of nursing practices.

PMID- 21168067
TI  - Is optical coherence tomography indicated for the evaluation of patients with
      neurofibromatosis type 1?

PMID- 21168068
TI  - The psychosocial effects of strabismus: effect of patient demographics on the AS
      20 score.
AB  - PURPOSE: The introduction of the AS-20 strabismus-specific quality-of-life
      questionnaire allows clinicians to quantify the effects of strabismus on adults
      for the first time. We correlated strabismic patients' demographic and clinical
      findings to their AS-20 scores. METHODS: A consecutive cohort of patients from an
      ongoing prospective study of adults with manifest strabismus was recruited. The
      patients' age, sex, socioeconomic status (SES), magnitude, and direction of
      deviation were correlated to their AS-20 scores. Patients' zip codes were used to
      derive a score for their SES based on the English 2007 Index of Multiple
      Deprivation score (IMD2007). RESULTS: A total of 61 questionnaires with all
      demographic and clinical data were available. The median magnitude of deviation
      was 20.4(Delta) in this group. The mean AS-20 score was 49.5 (SD 21.6). Women had
      significantly lower AS-20 scores than men (p = 0.02). There was no difference in
      AS-20 scores between individuals with eso- and exodeviations (p = 0.7). Multiple
      linear regression analysis shows female sex and lower SES to be significantly
      associated with lower AS-20 scores (p = 0.03 and p = 0.006, respectively).
      CONCLUSIONS: Strabismic patients who are female or live in a more deprived area
      have a significantly lower AS-20 score.

PMID- 21168070
TI  - Screening for refractive errors in children: the plusoptiX S08 and the Retinomax
      K-plus2 performed by a lay screener compared to cycloplegic retinoscopy.
AB  - PURPOSE: To evaluate the performance of the autorefractor Retinomax K-plus2 and
      the photoscreener plusoptiX S08 in measuring refractive errors by comparing them
      with cycloplegic retinoscopy (CR) and to assess limitations associated with their
      use. METHODS: Cross-sectional study to compare data from CR, performed by an
      orthoptist, to data from Retinomax K-plus2 and plusoptiX S08 performed by a lay
      screener. Sensitivity and specificity for the detection of significant refractive
      errors were determined according to American Academy of Pediatric Ophthalmology
      and Strabismus criteria. RESULTS: Two hundred children were included, with a mean
      age of 5.2 +/- 2.6 years (3 months to 11 years). Compared to CR, the plusoptiX
      S08 showed a mean difference of -1.13 +/- 1.25 D (95% limits of agreement [LOA], 
      3.59 to +1.32) for spherical equivalent (SE) and -0.23 +/- 0.53 D (LOA, -1.28 to
      +0.81) for the cylinder. Mean difference for the Retinomax K-plus2 before
      cycloplegia was -0.08 +/- 0.58 D (LOA, -1.23 to +1.06) for SE and 0.03 +/- 0.38 D
      (LOA, -0.72 to +0.78) for the cylinder; after cycloplegia -2.11 +/- 1.64 D (LOA, 
      5.33 to +1.10) for SE and -0.06 +/- 0.47 D (LOA, -0.98 to +0.86) for the
      cylinder. Sensitivity for detecting hyperopia >3.5 D with the plusoptiX S08 was
      33.3%, the Retinomax before cycloplegia 31.0% and after cycloplegia 84.6% and
      high for detecting myopia, astigmatism, and anisometropia. CONCLUSIONS: Retinomax
      K-plus2 and plusoptiX S08 have high sensitivity for the detection of myopia,
      astigmatism, and anisometropia compared to cycloplegic retinoscopy; however, when
      used without cycloplegia, hyperopia is underestimated.

PMID- 21168069
TI  - The accuracy of photoscreening at detecting treatable ocular conditions in
      children with Down syndrome.
AB  - BACKGROUND: Children with Down syndrome (DS) have an increased prevalence of
      ocular disorders, including amblyopia, strabismus, and refractive error. Health
      maintenance guidelines from the Down Syndrome Medical Interest Group recommend
      ophthalmologic examinations every 1 to 2 years for these children. Photoscreening
      may be a cost-effective option for subsequent screening evaluations after an
      initial complete examination, but no study has evaluated the accuracy of
      photoscreening in children with DS. The purpose of this study is to determine the
      sensitivity, specificity, and positive and negative predictive values of
      photoscreening in detecting treatable ocular conditions in children with DS.
      METHODS: Photoscreening and complete ophthalmologic evaluations were performed in
      50 consecutive 3- to 10-year-old children with DS. Sensitivity, specificity, and
      positive and negative predictive values were calculated with the use of
      ophthalmologic examination findings as the reference standard. RESULTS: Most
      children were able to complete photoscreening (94% with Medical Technology and
      Innovations [MTI] and 90% with Visiscreen OSS-C [VR]). Many children had an
      identified diagnosis on ophthalmologic examination (n = 46, 92%). Of these,
      approximately one-half (n = 27, 54%) had one or more condition(s) requiring
      treatment. Both the MTI and VR photoscreening devices had a sensitivity of 93%
      (95% confidence interval 0.76-0.99) for detecting treatable ocular conditions.
      The specificities for the MTI and VR photoscreening were 0.35 (0.18-0.57) and
      0.55 (0.34-0.74), respectively. CONCLUSIONS: Photoscreening is sensitive but less
      specific at detecting treatable ocular conditions in children with DS. In
      specific instances, the use of photoscreening in the DS population has the
      potential to save time and expense related to routine eye examinations,
      particularly in children with a normal baseline comprehensive examination.

PMID- 21168071
TI  - The base-to-base induced-tropia prism test for detection of amblyopia: a pilot
      study.
AB  - PURPOSE: To investigate the accuracy of the base-to-base prism test (BBPT), which
      entails inducing an esotropia with the use of base-in prisms before each eye, in
      the diagnosis of amblyopia. METHODS: Participants were consecutive patients
      recruited from a pediatric ophthalmology practice who were able to perform logMAR
      acuity testing. All participants underwent an orthoptic examination, including
      logMAR visual acuity testing, and a sensorimotor evaluation. Patients with an
      interocular difference of 2 or more lines were considered to have amblyopia.
      Fixation preference was assessed by use of both the vertical fixation test and
      the BBPT. The agreement between the BBPT and visual acuity was analyzed and
      compared with the agreement between the vertical fixation test and visual acuity.
      RESULTS: Fifty-one consecutive patients aged 4 to 17 (mean, 9.8 years; SD +/-
      3.4) were included, of whom 11 were diagnosed with amblyopia. Kappa analysis
      showed moderate but significant agreement between the BBPT and logMAR (kappa =
      0.453, p = 0.001), whereas the vertical fixation test demonstrated only a fair
      agreement (kappa = 0.254, p = 0.061). The overall sensitivity for the BBPT was
      72.7% (95% confidence interval [95% CI], 43.4%-90.3%) but only 40% for the
      vertical fixation test (95% CI, 16.8%-69.7%). For the BBPT, specificity was 80%
      (95% CI, 65.2%-89.5%); for the vertical fixation test, 78% (95% CI, 63.3%-88.0%).
      CONCLUSIONS: The BBPT appears to be more sensitive than the vertical fixation
      test for detecting amblyopia in our patient population. The 2 tests had similar
      specificity.

PMID- 21168072
TI  - The clinical profile of amblyopia in children younger than 3 years of age.
AB  - PURPOSE: Amblyopia in children >=3 years has been well described, but less is
      known about amblyopia in children <3 years of age. Here we describe the clinical
      characteristics of a large cohort of children <3 years of age with amblyopia and
      compare them with a previously described Pediatric Eye Disease Investigator Group
      amblyopic cohort aged 3 to 6 years. METHODS: A total of 250 consecutive children
      with amblyopia <3 years were referred by 16 pediatric ophthalmologists. RESULTS:
      The mean age at the initial diagnosis of amblyopia was 1.2 +/- 0.7 years. The
      cause of amblyopia was strabismus in 82%, anisometropia in 5%, and combined
      mechanism in 13%. Compared with the 3- to 6-year-old cohort, the proportion of
      amblyopia attributable to strabismus was significantly greater (p < 0.001),
      whereas both anisometropia and combined mechanism amblyopia were significantly
      less common (p < 0.001). Overall, 61% of amblyopia was diagnosed at the same
      visit during which strabismus and/or anisometropia was initially diagnosed; an
      additional 21% of amblyopia was diagnosed at the first follow-up visit 1 to 3
      months later. Compared with the 3- to 6-year-old cohort, amblyopic eye refractive
      error was significantly lower. CONCLUSIONS: Strabismic amblyopia was diagnosed
      much more commonly than anisometropic and combined-mechanism amblyopia in
      children <3 years. Anisometropic amblyopia may be difficult to detect in children
      <3 years, and/or strabismic amblyopia may be overdiagnosed by fixation
      preference. Alternatively, anisometropia may develop more commonly after 3 years
      of age or may require greater duration to cause amblyopia.

PMID- 21168073
TI  - Etiology and treatment of pediatric sixth nerve palsy.
AB  - PURPOSE: To describe the causes and treatment of sixth (abducens) nerve palsy in
      a series of pediatric patients. METHODS: This was a 14-year retrospective study
      of sixth nerve palsy in children under 14 years of age. Outcomes studied included
      horizontal deviation, degree of limitation of abduction, and head turn. Patients
      were treated with botulinum toxin injection at the time of diagnosis; surgery was
      indicated if treatment with botulinum toxin was unsuccessful. Success was defined
      as final deviation of orthotropia with no head turn or diplopia. RESULTS: Sixth
      nerve palsy was diagnosed in 15 patients (10 boys; mean age, 4.1 years) between
      1995 and 2008. Involvement was bilateral in 2 cases and unilateral in 13 (7 right
      eyes). Causes included neoplasm (4 cases), trauma (2), idiopathic (3), congenital
      (2), viral (2), and inflammatory (1). Neoplastic causes were associated with
      other neurologic signs. Recovery was spontaneous in 5 cases (2 idiopathic, 1
      traumatic, 1 congenital, and 1 inflammatory). Botulinum toxin was successful in 7
      of 10 patients treated, with follow-up surgery required in the remaining 3 cases.
      The final result was good in all cases. In all 15 patients, mean time from
      diagnosis to resolution was 39 months (range, 5 to 170 months). CONCLUSIONS:
      Neoplasms were the most frequent cause of sixth nerve palsy in our patient
      population. Recovery was spontaneous in one third of the patients. Most required
      treatment with botulinum toxin, which was successful in most cases. Surgery was
      successful after a single procedure.

PMID- 21168074
TI  - Optical coherence tomography in the evaluation of neurofibromatosis type-1
      subjects with optic pathway gliomas.
AB  - PURPOSE: Neurofibromatosis type 1 (NF1) is the most common neurocutaneous
      disorder, with an approximate incidence of 1 in 3,500. Optic pathway gliomas
      (OPGs) develop in 15% of individuals with NF1, commonly in childhood. OPGs are
      difficult to detect via a clinical inspection in children, often requiring
      magnetic resonance imaging (MRI). Given the significant visual risks associated
      with OPGs in NF1, there is a need for improved noninvasive techniques to diagnose
      OPGs in children; therefore, we studied optical coherence tomography (OCT) as a
      potential tool to assess optic nerve and retinal nerve fiber layer (RNFL)
      abnormalities. This prospective study was designed to evaluate OCT detection of
      RNFL loss from optic atrophy attributable to OPGs in a cohort of pediatric
      patients with NF1. METHODS: With the use of Stratus OCT, directed testing with
      the Fast Macular Thickness and Fast RNFL Thickness protocol scans were performed
      on 9 subjects with NF1 and known OPGs, 6 subjects with NF1 without OPGs, and 15
      controls. RESULTS: NF1 subjects with OPGs had thinner RNFLs and macula when
      compared with age-matched controls and to NF1 subjects without OPGs. After
      applying the equivalence equation, the average RNFL thickness and macular volume
      in NF1 subjects without OPGs was equivalent to controls. CONCLUSIONS: Our study
      suggests that OCT can be used to detect RNFL thinning secondary to OPGs in NF1
      subjects. This objective tool shows promise as a useful adjunct to routine
      clinical ophthalmologic evaluation in children with NF1.

PMID- 21168075
TI  - Longitudinal change in aphakic refraction after early surgery for congenital
      cataract.
AB  - PURPOSE: To characterize the longitudinal changes of refraction in aphakic eyes
      after early surgery for congenital cataract and to evaluate longitudinally
      measured aphakic refraction (individual vs group mean) as a noninvasive indicator
      of postoperative disturbances in ocular development. METHODS: Records of children
      who had cataract surgery during their first year of life between 1980 and 1995
      were obtained from a prospective, population-based study of congenital cataract.
      Only children with regular follow-up were included. Postoperative aphakic
      refraction was calculated at the corneal plane. Data were obtained up to 36
      months of age. RESULTS: The study included 28 children (49 eyes) who underwent
      surgery at a median age of 2.8 months (range, 0-9 months). The decrease of
      aphakic refraction at the corneal plane followed a logarithmic trend (R(2) =
      0.95). A total of 36 eyes followed this pattern, with no growth in 8 eyes and an
      increased growth rate in 1 eye with uncontrolled glaucoma and 4 eyes of 2
      children with Down syndrome. CONCLUSIONS: Most aphakic eyes follow a predictable,
      logarithmic change in refraction in the first 3 years of life, Longitudinal
      monitoring of refraction may prove to be a useful, noninvasive screening method
      for early detection of disturbances in aphakic eye growth.

PMID- 21168076
TI  - Wavefront analysis and ultrastructural findings in an eye with posterior
      lentiglobus.
AB  - An 8-year-old girl with unilateral posterior lenticoglobus underwent lens
      aspiration and intraocular lens implantation. Wavefront analysis performed before
      surgery to assess the surgical indication showed a higher-order aberration of
      0.502 MUm root mean square. After surgery, the value decreased to 0.132 MUm root
      mean square. Preoperative best-corrected visual acuity of 0.1 improved to 0.3
      postoperatively. Electron-microscopic examinations of the posterior capsule
      revealed unusual nodular structures and variations in capsular density.

PMID- 21168077
TI  - Orbital dermoid cyst with sinus tract mimicking ectopic cilia.
AB  - Dermoid cysts are the most common periorbital masses presenting in childhood. We
      describe an unusual case of a dermoid cyst presenting with black hairs emerging
      from a sinus tract on the upper eyelid and mimicking the appearance of ectopic
      cilia. Our case highlights the value of radiologic examinations in such cases.

PMID- 21168078
TI  - Langerhans cell histiocytosis of the uvea with neovascular glaucoma: diagnosis by
      fine-needle aspiration biopsy and management with intraocular bevacizumab and
      brachytherapy.
AB  - A 6-year-old boy with known multisystem Langerhans cell histiocytosis developed
      photophobia, conjunctival injection, iris neovascularization, and an
      iridociliochoroidal mass. Fine-needle aspiration biopsy revealed mononucleated
      and multinucleate histiocytes that demonstrated positive immunostaining for CD68
      and S100 consistent with Langerhans cell histiocytosis. Management with
      intracameral bevacizumab (1.25 mg/0.05 mL) resolved the iris neovascularization,
      and plaque radiotherapy (brachytherapy) resolved the mass rapidly and completely,
      preserving the patient's visual acuity and preventing glaucoma during the 10
      month follow-up.

PMID- 21168079
TI  - Bilateral herpes simplex-2 acute retinal necrosis with encephalitis in premature
      twins.
AB  - Acute retinal necrosis, caused by the herpes family of viruses, is a rapidly
      progressing ocular inflammatory disorder commonly reported in adults but rarely
      in children. The accepted diagnostic criteria include presence of 1 or more foci
      of retinal necrosis, rapid progression, circumferential spread, occlusive
      vasculopathy, and inflammation in the vitreous and anterior chamber. We report
      bilateral acute retinal necrosis with encephalitis due to herpes simplex virus
      (HSV-2) in newborn twins.

PMID- 21168080
TI  - Severe fibrosis of extraocular muscles after the use of lyophilized amniotic
      membrane in strabismus surgery.
AB  - Various techniques have been used to reduce adhesions after strabismus surgery.
      Wrapping the extraocular muscles with cryopreserved amniotic membrane has been
      reported to yield good results. In the case reported here, we used lyophilized
      amniotic membrane to wrap the extraocular muscles. Extensive adhesions developed,
      and inelastic, fibrotic muscles were discovered at a subsequent operation.

PMID- 21168081
TI  - Myopexy of the vertical rectus muscles using expanded polytetrafluoroethylene for
      management of a lost medial rectus muscle.
AB  - Strabismus due to a lost rectus muscle is uncommon. Surgical treatment of the
      condition by means of scleral augmented myopexy of the vertical rectus muscles
      can reduce the potential for anterior segment ischemia by leaving the vascular
      supply intact. We report a successful use of expanded polytetrafluoroethylene in
      this procedure to correct long-term exotropia caused by a lost medial rectus
      muscle.

PMID- 21168082
TI  - Cyclic exotropia in a child.
AB  - Cyclic strabismus is an uncommon disorder in which strabismus alternates with
      orthotropia in alternating 24-hour periods, although cycles of other lengths have
      also been described. Alternate-day exotropia is a rare form of cyclic strabismus
      which, to date, has been reported in few patients. We describe a case of
      alternate-day exotropia in a child who had previously undergone surgical
      correction of constant esotropia.

PMID- 21168083
TI  - Improvement in the field of binocular single vision following bilateral
      phacoemulsification with toric intraocular lens implantation in a patient with a
      partial third nerve palsy.
AB  - A 44-year-old female teacher with partial third (oculomotor) nerve palsy had a
      small central field of binocular single vision (BSV) following three strabismus
      procedures. Over several years her field of BSV constricted further, coincident
      with the development of myopia in one eye secondary to early lens change and in
      the presence of significant astigmatism. Following bilateral lens extraction with
      toric intraocular lens implants, her field of BSV reexpanded.

PMID- 21168084
TI  - Comparison of botulinum toxin with surgery as primary treatment for infantile
      esotropia.

PMID- 21168085
TI  - Comparison of botulinum toxin with surgery as primary treatment for infantile
      esotropia.

PMID- 21168087
TI  - Atypical Peters plus syndrome with new associations.

PMID- 21168089
TI  - Late spontaneous resolution of congenital Brown syndrome.

PMID- 21168091
TI  - Plasticity of motor cortex induced by coordination and training.
AB  - OBJECTIVE: To study the modifications induced by training of a coordinated
      movement on the primary motor cortex (M1) maps of one proximal muscle and one
      distal muscle activated alone and during their co-contraction. METHODS: Six
      healthy female sport students performed a 6-week training program during which
      they were trained in darts 3-4 times a week. At the end each subject had made
      more than 1200 throws. Transcranial magnetic stimulation (TMS) was used to map
      the proximal medial deltoid (MD) and the distal brachio-radialis (BR) muscle
      representations on M1. Motor evoked potentials (MEPs) amplitude and excitability
      curves were used to test corticomotor excitability. RESULTS: The cortical
      representation areas of each muscle separately increased after training. The
      cortical representation and the excitability curve of the BR muscle increased
      during co-activation with the MD. Combining co-contraction and training produced
      a further enlargement of the M1 representation of the BR muscle. CONCLUSIONS: The
      enlargement of the BR representation in M1 suggests the development of
      overlapping zones specifying functional synergies between distal and proximal
      muscles. SIGNIFICANCE: Our findings support the idea that training of a
      coordinated movement involving several muscles and joints requires an activity
      dependent coupling of cortical networks.

PMID- 21168092
TI  - Unnoticed small bowel perforation as a complication of lumbar discectomy.
AB  - BACKGROUND CONTEXT: Surgery for disc herniation is one of the most common traumas
      and neurosurgical procedures. Although discectomy has low morbidity, serious
      intra-abdominal complications can affect retroperitoneal structures, such as the
      large vessels, small intestine, and ureters. CASE REPORT: A 36-year-old woman in
      uncontrollable pain presented with left sciatic neuralgia in the L5 region.
      Magnetic resonance imaging revealed an extruded left paracentral hernia at L5-S1.
      With the patient in the decubitus prone position, trauma surgeons specializing in
      spine surgery performed an L5-S1 flavectomy and a simple discectomy.
      Intraoperative complications were not observed. About 4 hours after surgery, the
      patient reported sharp abdominal pain and had persistent hypotension. Emergency
      abdominal computed tomography showed hemoperitoneum in the pouch of Douglas and
      left parietocolic space. Laparoscopic exploration confirmed hemoperitoneum
      without visible cause, a seton perforation of the small intestine, and a few
      adhesions in the right iliac fossa that were consequences of previous
      appendectomy. A laparotomy was then performed. A lesion was discovered in the
      mesentery of the rectosigmoid junction coinciding with the S5-L1 space. A
      segmental bowel resection and mechanical side-to-side anastomosis, with drainage,
      were done. The patient recovered satisfactorily despite a surgical wound
      infection. DISCUSSION: Although bowel perforation after discectomy rarely occurs,
      spine surgeons must try to prevent them by being more cautious during surgery.
      General surgeons must be highly suspicious of the presence of an intra-abdominal
      complication when there are signs and symptoms of a postoperative acute abdomen.

PMID- 21168093
TI  - Tuberculosis of spine with neurological deficit in advanced pregnancy: a report
      of three cases.
AB  - BACKGROUND CONTEXT: Early decompression in spinal tuberculosis (TB) with complete
      paraplegia has a better prognosis in relation to the neurological recovery and
      deformity progression. Advanced pregnancy can complicate this picture in view of
      the various fetomaternal factors. The prevalent literature is inconclusive
      regarding the time and extent of surgical intervention. Delay in the surgical
      intervention may adversely affect the prognosis. PURPOSE: To emphasize the
      importance of early decompression in spinal TB complicated by neurological
      deficit in advanced pregnancy. STUDY DESIGN: A case report of three patients to
      analyze the surgical management of neurological deficit because of spinal TB in
      pregnancy. OUTCOME MEASURES: Neurological recovery, progression of deformity,
      healing of the TB lesion, and outcome of the pregnancy. METHODS: Three patients
      presented with spinal TB with neurological deficit complicating third trimester
      of pregnancy. The first patient was initially managed conservatively but was
      operated after a spontaneous abortion. The remaining two patients were managed by
      urgent Caesarean section followed by spinal decompression and fusion. RESULTS:
      The first patient who underwent delayed decompression showed good healing of the
      TB lesion but continued to have spastic paraparesis with kyphosis. This was later
      managed by repeat decompression and instrumented fusion, without neurological
      recovery. The other two patients treated by early decompression and fusion showed
      complete healing with neurological recovery. CONCLUSIONS: Early decompression and
      instrumented fusion in spinal TB, complicated by neurological deficit in advanced
      pregnancy, can give good results with respect to neurological recovery, healing
      of the lesion, and arrest of deformity progression. Neonatal prognosis depends on
      the fetal maturity. Antitubercular therapy is an essential component of the
      management; it poses little hazard of inducing congenital anomalies, but
      possibility of maternal drug toxicity should be considered.

PMID- 21168094
TI  - Incidence and prevalence of surgery at segments adjacent to a previous posterior
      lumbar arthrodesis.
AB  - BACKGROUND CONTEXT: Adjacent segment disease (ASD) after lumbar spinal fusion has
      been an important reason behind the development of nonfusion stabilization
      technology. However, the incidence, prevalence, and factors contributing to
      adjacent segment degeneration in the lumbar spine remain unclear. A range of
      prevalence rates for ASD have been reported in the lumbar spinal literature, but
      the annual incidence has not been widely studied in this region. Conflicting
      reports exist regarding risk factors, especially fusion length. PURPOSE: To
      determine the annual incidence and prevalence of further surgery for adjacent
      segment disease (SxASD) after posterior lumbar arthrodesis and examine possible
      risk factors. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Nine
      hundred twelve patients who underwent 1,000 consecutive posterior lumbar
      interbody fusion procedures, with mean follow-up duration of 63 months (range, 5
      months-16 years). OUTCOME MEASURES: Further surgery for ASD or surgery-free
      survival. METHODS: A postal and telephone survey. Follow-up rate: 91% of
      patients. The annual incidence and prevalence of ASD requiring further surgery
      were determined using Kaplan-Meier survivorship analysis. Cox proportional
      hazards (Cox) regression was used for multivariate analysis of possible risk
      factors. Significance was set at p<.05. RESULTS: Further surgery for ASD occurred
      following 130 of 1,000 or 13% of procedures at a mean time of 43 months (range,
      2.3-162 months). The mean annual incidence of SxASD over the first 10 years, in
      all patients, was 2.5% (95% confidence interval [95% CI], 1.9-3.1) with
      prevalences of 13.6% and 22.2% at 5 and 10 years, respectively. Cox regression
      modeling found that the number of levels fused (p<=.0003), age of the patient,
      fusing to L5, and performing an additional laminectomy adjacent to a fusion all
      independently affect the risk of SxASD. The mean annual incidence figures in the
      first 10 years after a lumbar fusion were 1.7% (95% CI, 1.3-2.2) after fusion at
      single levels, 3.6% (2.1-5.2) after two levels, and 5.0% (3.3-6.7) after three
      and four levels. The 5- and 10-year prevalences were 9% and 16%, 17% and 31%, and
      29% and 40% after single-, two-, and three-/four-level fusions, respectively. The
      risk of SxASD in patients younger than 45 years was one-quarter (95% CI, 10-64)
      the risk of patients older than 60 years (p=.003). A laminectomy adjacent to a
      fusion increases the relative risk by 2.4 times (95% CI, 1.1-5.2; p=.03).
      Stopping a fusion at L5 is associated with a 1.7-fold increased risk (95% CI, 1.2
      2.4; p=.007) of SxASD compared with a fusion to S1, for fusions of the same
      length. CONCLUSION: The overall annual incidence and predicted 10-year prevalence
      of further surgery for ASD after lumbar arthrodesis were 2.5% and 22.2%,
      respectively. These rates varied widely depending on the identified risk factors.
      Although young patients who underwent single-level fusions were at low risk,
      patients who underwent fusion of three or four levels had a threefold increased
      risk of further surgery, compared with single-level fusions (p<.0001), and a
      predicted 10-year prevalence of 40%.

PMID- 21168095
TI  - Adjacent segment degeneration after lumbar spinal fusion: risk factors and
      implications for clinical practice.

PMID- 21168096
TI  - Postoperative anterior spondylodiscitis after posterior pedicle screw
      instrumentation.
AB  - BACKGROUND CONTEXT: Postoperative wound infection is a well-recognized
      complication of spinal surgery. The infection occurs usually at the posterior
      wound after posterior spinal surgery. To the best of our knowledge, no report
      exists regarding treatment of anterior spondylodiscitis after posterior pedicle
      screw instrumentation. PURPOSE: Audit of our protocols for the diagnosis and
      management of anterior spondylodiscitis after posterior pedicle screw
      instrumentation. STUDY DESIGN/SETTING: A retrospective study of patients with
      anterior spondylodiscitis after posterior pedicle screw instrumentation, who
      received treatment accordingly. PATIENT SAMPLE: Eleven patients were included.
      OUTCOME MEASUREMENT: The outcomes were evaluated clinically by the Oswestry
      Disability Index (ODI) and visual analog scale (VAS). The status of the anterior
      fusion was assessed according to the Bridwell grading system. Eradication of
      infection was determined by the level of C-reactive protein (CRP) and erythrocyte
      sedimentation rate (ESR). METHODS: From 1997 to 2008, 6,120 patients with
      degenerative spinal diseases and osteoporotic spine fractures were treated with
      posterolateral-instrumented fusion, and postoperative posterior infection was
      found in 135 (2.2%) patients. Postoperative anterior spondylodiscitis was noted
      in 11 patients. The 11 patients with anterior spondylodiscitis after posterior
      pedicle screw instrumentation underwent combined posterior surgery and anterior
      debridement with fusion simultaneously or in staged operations. The clinical
      outcomes were evaluated by the ODI and VAS. The status of the anterior fusion was
      assessed according to the Bridwell grading system. Eradication of infection was
      determined by the level of CRP and ESR. RESULTS: Postoperative anterior infection
      was diagnosed between 2 and 36 months (average, 14.8 months) after posterior
      surgery. The average period of recurrent axial pain and the diagnosis of
      infection was 19.7 weeks (2-24 weeks). The mean ESR was 66.4 mm/h (range, 20-95
      mm/h) and CRP was 52.7 mg/L (range, 8.4-129 mg/L). All patients received
      parenteral antibiotics for 4 to 6 weeks, followed by oral antibiotics for a total
      of 3 months according to sensitivity tests after surgery. All patients had
      complete eradication of infection. The mean VAS improved from 7.9 preoperatively
      to 2.0 postoperatively. The mean ODI score improved from 44 to 21.1. Based on the
      Bridwell anterior fusion grading system, nine (82%) patients achieved Grade I
      fusion and two (18%) patients achieved Grade II fusion. CONCLUSIONS: Anterior
      spine infection may occur after posterior pedicle screw instrumentation. Eleven
      patients with anterior spondylodiscitis, which developed after posterior pedicle
      screw instrumentation, were successfully treated by combined posterior surgery
      and anterior debridement with fusion simultaneously or in staged operations.
      LEVEL OF EVIDENCE: Level IV, case series study.

PMID- 21168097
TI  - Load and the spine. How does the Goldilocks principle apply?

PMID- 21168098
TI  - Bupivacaine--the deadly friend of intervertebral disc cells?
AB  - BACKGROUND CONTEXT: Bupivacaine is commonly used as an adjunct during provocative
      discography and is administered intradiscally in patients with discogenic back
      pain. Recent studies demonstrated that bupivacaine is cytotoxic for articular
      chondrocytes in vitro at clinically used concentrations (0.25%-0.5%). PURPOSE: To
      analyze a concentration-dependent effect of bupivacaine on cell viability and
      gene expression of human intervertebral disc (IVD) cells in an in vitro model.
      STUDY DESIGN: In vitro cell culture study. PATIENT SAMPLE: Disc cells were
      isolated from human disc biopsies from 11 patients undergoing surgery because of
      degenerative disc disease or disc herniation. OUTCOME MEASURES: Cell viability
      and gene expression after exposure to bupivacaine. METHODS: Human IVD cells were
      treated with different concentrations of bupivacaine for 2 (n=5) or 18 hours
      (n=5) and analyzed for cell viability and proliferation (3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyl tetrazolium bromide assay). Additionally, cells were
      prestimulated with interleukin-1 beta (IL-1beta) (5 ng/mL) to increase the levels
      of proinflammatory cytokines and matrix-degrading enzymes and thereafter treated
      with 0.75 mmol bupivacaine (as determined in the cell viability test) for 2 (n=5)
      or 18 hours (n=5). Prestimulated cells with or without bupivacaine treatment were
      analyzed for gene expression of IL-1beta, IL-6, IL-8, tumor necrosis factor-alpha
      (TNF-alpha), cyclooxygenase-2 (COX-2), matrix metalloproteinase-3 (MMP3), MMP9,
      MMP13, and a disintegrin and metalloproteinase with thrombospondin motifs 4
      (ADAMTS4) using real-time reverse transcription-polymerase chain reaction.
      Statistical analysis was performed by using the Mann-Whitney U test with a
      significance level of p<.05. RESULTS: After 18 hours, bupivacaine exhibited
      either a cytotoxic or a proliferative effect on human IVD cells, depending on the
      concentration. Similar but lower effects could be observed already after 2 hours.
      With a concentration of 0.75 mmol (proliferative effect), bupivacaine
      significantly decreased messenger RNA levels of TNF-alpha, COX-2, MMP13, and
      ADAMTS4 after 18 hours. In contrast, expression of IL-6, IL-8, and MMP9 did not
      differ; expression of IL-1beta and MMP3 was stimulated with 0.75 mmol. After 2
      hours, we observed a reduction in the expression of COX-2, MMP3, MMP13, and
      ADAMTS4, without any effect regarding IL-1beta. CONCLUSIONS: Application of
      bupivacaine in clinically relevant concentrations was toxic for IVD cells in
      vitro. A low concentration stimulated cell proliferation and reduced gene
      expression of certain matrix-degrading enzymes and proinflammatory cytokines. If
      these results can be corroborated in tissue explant models or animal studies,
      caution regarding provocative discography with bupivacaine is prompted.

PMID- 21168099
TI  - Instrumentation of the osteoporotic spine: biomechanical and clinical
      considerations.
AB  - BACKGROUND CONTEXT: Osteoporosis is a major health-care problem that is
      increasing in magnitude with the aging population. Such patients are more prone
      to develop painful and debilitating spinal deformities but are difficult to
      treat. Currently, no definitive treatment algorithm has been established.
      PURPOSE: To review the failure modes of instrumentation and novel surgical
      treatments of spinal deformities in patients with osteoporosis with the goal of
      improving surgical care. STUDY DESIGN/SETTING: Review article. METHODS: We
      systematically searched PubMed for articles regarding instrumentation failure
      modes and surgical treatments of spinal deformities in patients with osteoporosis
      and summarized current treatment options. RESULTS: The surgical treatment options
      are severely limited because of the tendency for instrument failure secondary to
      pullout and subsidence, leading to revision procedures; multiple levels and
      multiple fixation points are recommended to minimize the risk. The literature
      supports the use of vertebroplasty in conjunction with pedicle screw-based
      instrumentation for treating more severe spinal deformities. Other techniques and
      modifications with evidence of reduced failure risk are bicortical screws,
      hydroxyapatite coatings, double screws, and expandable screws. Anterior
      approaches may provide another avenue of treatment, but only a few studies have
      been conducted on these implants in patients with osteoporosis. CONCLUSIONS:
      Spinal deformities in patients with osteoporosis are difficult to treat because
      of their debilitating and progressive nature. Novel surgical approaches and
      instruments have been designed to decrease construct failures in this patient
      population by reducing implant pullout, subsidence, and incidence of revision
      surgery. The success of these techniques depends on integrating biomaterial,
      biologic, and biomechanical aspects with clinical considerations. Synthesizing
      this myriad of aspects will lead to improved treatment options for patients with
      osteoporosis who are suffering from spinal deformities.

PMID- 21168100
TI  - An evidence-based clinical guideline for the diagnosis and treatment of cervical
      radiculopathy from degenerative disorders.
AB  - BACKGROUND CONTEXT: The North American Spine Society (NASS) Evidence-Based
      Clinical Guideline on the Diagnosis and Treatment of Cervical Radiculopathy from
      Degenerative Disorders provides evidence-based recommendations on key clinical
      questions concerning the diagnosis and treatment of cervical radiculopathy from
      degenerative disorders. The guideline addresses these questions based on the
      highest quality clinical literature available on this subject as of May 2009. The
      guideline's recommendations assist the practitioner in delivering optimum
      efficacious treatment of and functional recovery from this common disorder.
      PURPOSE: Provide an evidence-based educational tool to assist spine care
      providers in improving quality and efficiency of care delivered to patients with
      cervical radiculopathy from degenerative disorders. STUDY DESIGN: Systematic
      review and evidence-based clinical guideline. METHODS: This report is from the
      Cervical Radiculopathy from Degenerative Disorders Work Group of the NASS'
      Evidence-Based Clinical Guideline Development Committee. The work group consisted
      of multidisciplinary spine care specialists trained in the principles of evidence
      based analysis. Each member of the group formatted a series of clinical questions
      to be addressed by the group. The final questions agreed on by the group are the
      subjects of this report. A literature search addressing each question using a
      specific search protocol was performed on English language references found in
      MEDLINE, EMBASE (Drugs and Pharmacology), and four additional evidence-based
      databases. The relevant literature was then independently rated by a minimum of
      three reviewers using the NASS-adopted standardized levels of evidence. An
      evidentiary table was created for each of the questions. Final recommendations to
      answer each clinical question were arrived at via work group discussion, and
      grades were assigned to the recommendations using standardized grades of
      recommendation. In the absence of Levels I to IV evidence, work group consensus
      statements have been developed using a modified nominal group technique, and
      these statements are clearly identified as such in the guideline. RESULTS:
      Eighteen clinical questions were formulated, addressing issues of natural
      history, diagnosis, and treatment of cervical radiculopathy from degenerative
      disorders. The answers are summarized in this article. The respective
      recommendations were graded by the strength of the supporting literature, which
      was stratified by levels of evidence. CONCLUSIONS: A clinical guideline for
      cervical radiculopathy from degenerative disorders has been created using the
      techniques of evidence-based medicine and best available evidence to aid both
      practitioners and patients involved with the care of this condition. The entire
      guideline document, including the evidentiary tables, suggestions for future
      research, and all references, is available electronically at the NASS Web site
      (www.spine.org) and will remain updated on a timely schedule.

PMID- 21168101
TI  - Vascular causes of radiculopathy: a literature review.
AB  - BACKGROUND CONTEXT: Vascular etiologies are a significant source of
      radiculopathy. The entities that are reviewed here include epidural spinal
      hematoma, subdural spinal hematoma, spinal arteriovenous malformation, vertebral
      hemangioma, spinal epidural cavernous hemangioma, vertebral artery anomalies
      (both tortuosity and dissection), aortic aneurysm, hemorrhagic synovial cysts,
      ligamentum flavum hematoma, and venous varices. The incidence, pathophysiology,
      typical clinical presentation, appropriate diagnostic workup, and management are
      summarized. PURPOSE: To review and summarize various vascular causes of
      radiculopathy and how it impacts the management of patients with radicular spinal
      pain. STUDY DESIGN: Literature review. METHODS: An extensive literature review
      was done on each of the vascular entities and their presentation as
      radiculopathy. RESULTS: Vascular etiologies of radiculopathy may be
      underestimated in the literature. Imaging in addition to the history and physical
      examination is essential to identifying vascular sources of radiculopathy and
      establishing correct treatment. CONCLUSIONS: In examining patients with radicular
      pain, extraspinal causes of radiculopathy including vascular entities should be
      included in the differential. Knowledge of the incidence, pathophysiology,
      clinical presentation, and management of the possibly underreported various
      vascular causes of radiculopathy increase the ability of the physician to provide
      optimal care for the patient. A key aspect to identifying such vascular lesions
      is appropriate imaging for documenting the source of radiculopathy. Blind
      injections, done without appropriate imaging for identifying the cause of
      radiculopathy, and also performed without fluoroscopic guidance, increase not
      only the risk of misdiagnosis but also the comorbidities associated with spinal
      injections.

PMID- 21168102
TI  - A lumbar disc herniation mimicking spinal tumor with intra- and extradural
      components.

PMID- 21168103
TI  - Intradural intraradicular disc herniation in the lumbar spine: apropos of a new
      case.

PMID- 21168104
TI  - Spinal manipulation for headache?

PMID- 21168106
TI  - Yoga clinical research review.
AB  - In this paper recent research is reviewed on the effects of yoga poses on
      psychological conditions including anxiety and depression, on pain syndromes,
      cardiovascular, autoimmune and immune conditions and on pregnancy. Further, the
      physiological effects of yoga including decreased heartrate and blood pressure
      and the physical effects including weight loss and increased muscle strength are
      reviewed. Finally, potential underlying mechanisms are proposed including the
      stimulation of pressure receptors leading to enhanced vagal activity and reduced
      cortisol. The reduction in cortisol, in turn, may contribute to positive effects
      such as enhanced immune function and a lower prematurity rate.

PMID- 21168107
TI  - Role of naturopathy and yoga treatment in the management of hypertension.
AB  - AIM: The primary aim was to study the effect of naturopathy and yoga
      interventions in treatment of mild to moderate hypertension. DESIGN: The
      variables of interest were measured at the beginning and end of the intervention
      using a pre-post design. SETTING: The study was conducted by INYS medical
      research society in Jindal Nature Cure Institute, Bangalore. SUBJECTS: A total of
      104 subjects, already diagnosed with mild to moderate hypertension and on
      treatment with antihypertensive medicines were included in study. INTERVENTIONS:
      The intervention consisted of various inpatient administration of different
      naturopathy treatments, yoga therapies, low calorie and low sodium diet for 21
      days. Antihypertensive medicines were withdrawn for some patients in one week
      based upon response to the treatment. OUTCOME MEASURES: The outcome measures were
      values of diastolic and systolic blood pressure and body weight. Subjects were
      followed for a period of one year after every 3 months. RESULTS: After starting
      nonpharmacological approach of naturopathy and yoga, Systolic blood pressure came
      down from mean of 139.6 to 129.6 where as it came down from 91.2 to 86.1 for
      diastolic blood pressure. At the same time favorable effect was also seen in
      other variables like lipid profile and body weight. At the end of one year out of
      57 patients who came for follow-up, 14 cases were found to have blood pressure
      within normal ranges without any medication over the previous 12 months.
      CONCLUSION: Naturopathy and yoga therapy can be considered as a valuable
      nonpharmacological approach in treatment of hypertension.

PMID- 21168108
TI  - Effects of yoga on balance and gait properties in women with musculoskeletal
      problems: a pilot study.
AB  - OBJECTIVES: The purpose of the present study is to investigate the effects of
      yoga on balance and gait properties in women with musculoskeletal problems.
      DESIGN: Twenty-seven women (30-45 years old) with musculoskeletal problems, such
      as osteoarthritis and low-back pain, were included in the present study. The
      patients participated in 8 sessions (twice weekly for 4 weeks) of a yoga program
      which included asanas, stretching exercises, and breathing techniques. MAIN
      OUTCOME MEASURES: Patients' static balance measurements and gait parameters were
      determined before and after the study using a stabilometer and a gait trainer,
      respectively. RESULTS: Post-study values of patients' gait parameters were found
      to be statistically higher than their pre-study values (p < 0.05) The values of
      patients' balance addressed anterior and right positions with patients' eyes open
      and subsequently closed pre-treatment. However, it was notable that balance post
      treatment was minimal when subjects eyes were open or closed. Anterior-posterior
      values and right-left values were almost equal after treatment. DISCUSSION: The
      results showed that yoga has a positive effect on balance and gait parameters of
      women with gait and balance disturbances that are caused by musculoskeletal
      problems. It is feasible to conclude that asanas and stretching exercises
      included in the yoga program brought about such a positive effect, and therefore
      it is possible to use yoga programs to solve problems caused by musculoskeletal
      disorders.

PMID- 21168109
TI  - An investigation into the effectiveness of traditional Chinese acupuncture (TCA)
      for chronic stress in adults: a randomised controlled pilot study.
AB  - AIMS: The aim of this exploratory, pragmatic randomised controlled trial was to
      investigate the effectiveness of traditional Chinese acupuncture (TCA), using an
      individually targeted treatment protocol delivered by a traditionally trained
      Chinese acupuncturist. The trial examined the treatment of chronic stress as
      perceived and reported by the participants, with all its diversity of presenting
      symptoms, rather than using a cohort approach based on a single stress-related
      symptom. METHODS: Participants (n=18) with high self-reported stress levels were
      randomised into 3 groups. Group 1 received weekly TCA for 5 weeks; group 2
      received weekly attention only (practitioner present and participant supine) for
      5 weeks and group 3 acted as a waiting list control. The Perceived Stress Scale
      14 (PSS-14) and the Measure Yourself Medical Outcome Profile (MYMOP) were
      completed before and after a 5-week intervention. RESULTS: After 5 weeks, group 1
      reported significant changes in MYMOP profile score and both MYMOP reported
      symptoms (p<0.05); group 2 had significant changes in MYMOP profile score and 1
      symptom (p<0.05); group 3 showed no changes. The PSS-14 scores decreased in all 3
      groups, but the difference between pre- and post-study within and between the
      groups did not reach significance in this small study. In addition, there were
      self-reports of improvements for group 1 for other health problems encountered
      during treatment. LIMITATIONS AND CONCLUSIONS: The lack of clarity concerning the
      definition of stress makes it complex to investigate. This pilot study suggests
      that TCA may be successful in treating the symptoms of stress, through a
      combination of specific and non-specific effects; but may not relate directly to
      how a person perceives their stress.

PMID- 21168110
TI  - Increased mindfulness--the active component of the mindfulness-based stress
      reduction program?
AB  - While there is growing consensus that Mindfulness-Based Stress Reduction (MBSR)
      is an effective program for patients with a wide range of health problems, little
      is known with regard to the processes underlying benefits seen following the
      program. Herein we examined the relationship between increases in mindfulness and
      improvements in patient outcomes. We sought to determine if there was a
      relationship between the practice of various types of meditation taught during
      the program and post-MBSR results. Eighty-three chronic ill patients provided pre
      and post-MBSR data. An increase in mindfulness was significantly related to
      reductions in depressive symptoms, stress, medical symptoms and an increase in
      overall sense of coherence. However, the relationship between practice and
      outcomes was less evident. Future research is needed to identify which factors
      lead to an increase in mindfulness.

PMID- 21168111
TI  - The chiropractic care of children with "growing pains": a case series and
      systematic review of the literature.
AB  - OBJECTIVE: To describe the successful chiropractic care of two pediatric patients
      with complaints of "growing pain." CLINICAL FEATURES: A 23/4-yr-old female and
      31/2-yr-old male were presented by their mothers with complaints of "growing
      pains" that awakened both patients at night. The girl's problem began 3 months
      prior to care with awakening due to leg pain at 1-2 nights weekly in the first
      month and progressed to 5-6 nights per week in the month prior to presentation.
      The boy's growing pain was of "several months" duration that awakened the patient
      2-3 nights per week. The parents of both children denied trauma or an "organic"
      cause to their children's pain complaints. Spinal segmental dysfunctions were
      noted in both patients at the lumbosacral spine. INTERVENTION AND OUTCOME: Spinal
      manipulative therapy (SMT) characterized as high velocity, low amplitude thrusts
      to sites of segmental dysfunction was rendered to both patients. Following a
      trial of care (i.e., 3 visits scheduled over a 3-week period and 4 visits over a
      period of 14 weeks), the patient's symptoms resolved and were released from care.
      CONCLUSION: This case series provides support on the effectiveness of
      chiropractic SMT for children with complaints of "growing pain." We support
      further research in the care of similar patients.

PMID- 21168112
TI  - The effects of acupressure on primary dysmenorrhea: a randomized controlled
      trial.
AB  - OBJECTIVE: The current study was conducted to evaluate the effect of acupressure
      on primary dysmenorrhea in Iranian medical sciences students. DESIGN: A
      randomized controlled pre and post-test design was employed to verify the effects
      of SP6 acupressure on dysmenorrhea. SETTING: A total of 30 young college female
      students with primary dysmenorrhea were randomly allocated to intervention (n =
      15) and control (n = 15) groups. INTERVENTION: The intervention group received
      SP6 acupressure during menstruation cycle and the control group received light
      touch on the SP6 acupoint. Using a Visual Analog Scale, the severity of
      dysmenorrhea was assessed prior to and immediately, 30 min, 1, 2, and 3 h
      following treatment. MAIN OUTCOME MEASURES: Data were analyzed using X(2), t-test
      and ANOVA statistical tests. RESULTS: Significant differences were observed in
      the scores of dysmenorrhea between the two groups immediately after (3.50 +/-
      1.42 vs. 5.06 +/- 1.43, p = 0.004) and also 3 h after treatment (1.66 +/- 1.98
      vs. 4.80 +/- 1.37, p = 0.000). CONCLUSIONS: Acupressure on the SP6 meridian can
      be an effective non-invasive nursing intervention for alleviating primary
      dysmenorrhea and its effects last for 3 h post-treatment.

PMID- 21168113
TI  - Effectiveness of aroma massage on advanced cancer patients with constipation: a
      pilot study.
AB  - PURPOSE: The purpose of this study was to verify the effect of aroma massage on
      constipation in advanced cancer patients. METHODS: This study employed a
      randomized control group pre- and post test design and included an aroma massage
      group, plain massage group, and control group. To evaluate the effect of
      aromatherapy, the degree of constipation was measured using a constipation
      assessment scale, severity level of constipation and the frequency of bowel
      movements. Data was analyzed by repeated measures of Mann-Whitney U test,
      Wilcoxon signed ranks test, Spearman's rho and ANOVA using SPSS program. RESULTS:
      The score of the constipation assessment scale of the aroma massage group was
      significantly lower than the control group. Apart from the improvement in bowel
      movements, the results showed significantly improved quality of life in physical
      and support domains of the aroma massage group. CONCLUSION: The findings of this
      study suggest aroma massage can help to relieve constipation in patients with
      advanced cancer.

PMID- 21168114
TI  - Perceptions of complementary therapies among Swedish registered professions in
      surgical care.
AB  - There is increasing interest in complementary and alternative medicine (CAM)
      among healthcare professions. However, no studies have been conducted in Sweden
      or in a surgical context. The aim of this study is to describe different
      perceptions of complementary therapies among registered healthcare professions in
      Swedish surgical care. Sixteen interviews were conducted with registered
      physicians, nurses, physiotherapists and clinical dieticians at a Swedish
      university hospital. Analysis was made with a phenomenographic research approach.
      The findings showed variations in perceptions of the definition of complementary
      therapies. A constructive approach toward use was observed, but there was a
      conflict in matters of indications and contraindications, and also criticism over
      a lack of knowledge. There was seen to be a need for education to be able to act
      professionally. Scepticism over high costs of treatment was highlighted. In
      conclusion, a need for policies on management, education and research in the
      field of CAM should be addressed.

PMID- 21168115
TI  - Healing advantages of lavender essential oil during episiotomy recovery: a
      clinical trial.
AB  - Episiotomy is the most common perineal incision in obstetric and midwifery.
      Nowadays alternative and complementary methods such as Aromatherapy using
      essential oils are established as an alternative therapy. This research was
      carried out to assess the effect of lavender oil in wound healing. This
      randomized control trial was conducted on 120 primiparous women with singleton
      pregnancy, without any acute and chronic disease and allergy who had undergone
      normal spontaneous vaginal delivery and episiotomy. They were randomly allocated
      in case and control groups. Case group received lavender oil and controls
      received povidone-iodine. Incision sites were assessed on the 10th day
      postpartum. 25 out of 60 women in lavender group and 17 mothers in control group
      had no pain (p = 0.06). There was no significant difference between two groups in
      surgery site complications. However, redness in lavender group was significantly
      less than controls (p < 0.001). This study suggests application of lavender
      essential oil instead of povidone-iodine for episiotomy wound care.

PMID- 21168116
TI  - Qigong training and effects on stress, neck-shoulder pain and life quality in a
      computerised office environment.
AB  - BACKGROUND: Qigong is a Chinese health promoting exercise with a rhythmic pattern
      of slow movements and breathing affecting the autonomous nervous system.
      OBJECTIVES: To examine the implementation of Qigong for half an hour daily in a
      computerised office, and to study effects on health state, general health, neck
      shoulder and lumbar spine symptoms and stress after six weeks training DESIGN: A
      crossover intervention study with 37 employees randomised in two groups. A
      questionnaire was completed one week before starting study and every second week
      during the training period. After 6 weeks the first group stopped and the second
      group started the training. RESULTS: There was a small significant improvement of
      neck pain and disability following therapy. CONCLUSION: Qigong training may
      reduce neck disability in office workers. A longer training period might be
      needed in further Qigong studies in healthy, normal populations.

PMID- 21168117
TI  - An examination of the effect of castor oil packs on constipation in the elderly.
AB  - This research, conducted at two rest homes in Manisa, Turkey, was undertaken to
      examine the effect of castor oil pack (COP) administrations on constipation in
      the elderly. Study participants were monitored for 7 days before, 3 days during,
      and 4 days after COP administration utilizing the Recall Bias and Visual Scale
      Analog (RB-VSAQ) as well as the Standard Diary developed by Pamuk et al. Wilcoxon
      Signed Ranks, Repeated Measures, Bonferroni, and Mann-Whitney U tests were used
      for data analysis. Eighty percent of study subjects had been constipated for 10
      years or longer. COP administration did not have an effect on the number of bowel
      movements or amount of feces, but decreased the feces consistency score,
      straining during defecation and feeling of complete evacuation after a bowel
      movement, thus decreasing symptoms of constipation. We conclude that COP may be
      used for controlling symptoms of constipation.

PMID- 21168119
TI  - [Primary rhinopharyngeal tuberculosis: an unusual location].
AB  - We describe a primary rhinopharyngeal tuberculosis case in a woman who presented
      with an asymptomatic mass found incidentally on a MRI scan. Histopathological
      examination of the biopsy specimen showed granulomatous inflammation and caseous
      necrosis. Anti-tuberculosis therapy was applied for a 6-month period, after which
      nasopharyngeal examination was normal. This case supports the necessity of
      including tuberculosis in the differential diagnosis for a rhinopharyngeal mass.

PMID- 21168120
TI  - Effect of glaucoma on corneal graft survival according to indication for
      penetrating keratoplasty.
AB  - PURPOSE: To determine whether the risk of graft failure in patients with glaucoma
      is dependent on the indication for penetrating keratoplasty (PK). DESIGN:
      Retrospective cohort study. METHODS: All patients on the United Kingdom
      Transplant Registry undergoing their first PK over a 7-year period with at least
      1 year of follow-up were included. Data were collected on indication for PK,
      presence and management of glaucoma, graft diameter, recipient risk factors, and
      graft survival. Kaplan-Meier survival curves, a Cox regression model, and chi(2)
      and t tests were used in group comparisons. RESULTS: A total of 6255 transplants
      in eyes without glaucoma and 1994 in eyes with glaucoma were analyzed. Three-year
      transplant survival was 86% and 72% respectively (P < .0001), and 73% in eyes
      with medically managed glaucoma compared to 63% in surgically managed glaucoma (P
      = .07). Glaucoma patients undergoing PK for pseudophakic bullous keratopathy or
      Fuchs dystrophy had significantly increased relative risks of graft failure (1.5
      and 1.9 with topical and 2.0 and 3.1 with oral antiglaucoma medication
      respectively, compared to those without glaucoma). There was no equivalent
      significant difference for those with keratoconus, previous noncataract ocular
      surgery, trauma, or noninfectious ulcerative keratitis. Endothelial
      decompensation accounted for a significantly greater proportion of graft failure
      in recipients with glaucoma (topical [9%] and oral medication [13%]) than in
      those without glaucoma (3%) (P < .001). DISCUSSION: The presence of glaucoma
      carries an increased risk of graft failure, in particular from endothelial
      decompensation. This risk is, however, also dependent on the indication for PK,
      with transplants undertaken for primary corneal endothelial disease carrying a
      higher risk.

PMID- 21168121
TI  - Deletion of the delta opioid receptor gene impairs place conditioning but
      preserves morphine reinforcement.
AB  - BACKGROUND: Converging experimental data indicate that delta opioid receptors
      contribute to mediate drug reinforcement processes. Whether their contribution
      reflects a role in the modulation of drug reward or an implication in conditioned
      learning, however, has not been explored. In the present study, we investigated
      the impact of delta receptor gene knockout on reinforced conditioned learning
      under several experimental paradigms. METHODS: We assessed the ability of delta
      receptor knockout mice to form drug-context associations with either morphine
      (appetitive)- or lithium (aversive)-induced Pavlovian place conditioning. We also
      examined the efficiency of morphine to serve as a positive reinforcer in these
      mice and their motivation to gain drug injections, with operant intravenous self
      administration under fixed and progressive ratio schedules and at two different
      doses. RESULTS: Mutant mice showed impaired place conditioning in both appetitive
      and aversive conditions, indicating disrupted context-drug association. In
      contrast, mutant animals displayed intact acquisition of morphine self
      administration and reached breaking-points comparable to control subjects. Thus,
      reinforcing effects of morphine and motivation to obtain the drug were
      maintained. CONCLUSION: Collectively, the data suggest that delta receptor
      activity is not involved in morphine reinforcement but facilitates place
      conditioning. This study reveals a novel aspect of delta opioid receptor function
      in addiction-related behaviors.

PMID- 21168122
TI  - Neural correlates of error monitoring modulated by atomoxetine in healthy
      volunteers.
AB  - BACKGROUND: Atomoxetine is a selective norepinephrine reuptake inhibitor
      clinically used for treatment of attention-deficit/hyperactivity disorder. In
      healthy control subjects, doses of 40 mg or 60 mg improved inhibitory control in
      combination with modulation of prefrontal cortex functioning. We investigated the
      effects of atomoxetine (80 mg) on error monitoring as a second key component of
      cognitive control. METHODS: Twelve healthy, male volunteers were included in a
      randomized double-blind, placebo-controlled, within-subjects design to examine
      the effects of a single dose of atomoxetine on neural activities during a
      combined Eriksen flanker-Go/NoGo task as measured by functional magnetic
      resonance imaging. RESULTS: Behaviorally, atomoxetine led to a significant
      increase in failed inhibition. Functionally, interaction analysis revealed a
      significant increase of the error signal (incorrect minus correct NoGo trials)
      under atomoxetine in bilateral inferior frontal cortex and presupplementary motor
      area. Drug-dependent increases in error signaling did not correlate with
      increased error rates. Analysis of neuropsychological data indexed a significant
      increase in phasic alertness. CONCLUSIONS: Results support that atomoxetine
      increases neural sensitivity for errors in healthy control subjects, possibly due
      to an accentuated representation of the task set. However, this gain was
      accompanied by deterioration in inhibitory control, possibly reflecting a shift
      beyond the optimal working range of the norepinephrine system.

PMID- 21168123
TI  - Longitudinal volume reductions in people at high genetic risk of schizophrenia as
      they develop psychosis.
AB  - BACKGROUND: Structural differences between the brains of people with
      schizophrenia and control subjects are highly replicated but the timing and
      clinical correlates are unclear. In the Edinburgh High Risk Study, we have
      followed up 162 individuals at high genetic risk of schizophrenia and 36 healthy
      control subjects over 10 years. METHODS: Participants received detailed clinical
      and up to five structural magnetic resonance imaging (MRI) assessments at 2-year
      intervals. All 436 MRI scans acquired were parcellated and adjusted for between
      scanner differences. The trajectory of any structural MRI changes was then
      investigated using mixed effects analysis of variance. RESULTS: Seventeen of the
      146 high-risk subjects who were scanned developed schizophrenia over the 8 years
      of the study. People at high genetic risk of schizophrenia had significantly
      greater reductions over time than the control group for whole brain volume and
      left and right prefrontal and temporal lobes. Greater prefrontal reductions were
      shown in high-risk subjects who subsequently became unwell compared with those
      who did not. These changes were significantly associated with increasing severity
      of psychotic symptoms. CONCLUSIONS: Individuals at high genetic risk of
      schizophrenia exhibited reductions in cerebral volume that were not found in
      control subjects. Changes in brain structure were also associated with increasing
      psychotic symptom severity as people developed schizophrenia. The progressive
      reductions found in those who went on to develop schizophrenia suggest an
      additional brain insult near to the time of onset.

PMID- 21168124
TI  - Deficits in positive reinforcement learning and uncertainty-driven exploration
      are associated with distinct aspects of negative symptoms in schizophrenia.
AB  - BACKGROUND: Negative symptoms are core features of schizophrenia (SZ); however,
      the cognitive and neural basis for individual negative symptom domains remains
      unclear. Converging evidence suggests a role for striatal and prefrontal dopamine
      in reward learning and the exploration of actions that might produce outcomes
      that are better than the status quo. The current study examines whether deficits
      in reinforcement learning and uncertainty-driven exploration predict specific
      negative symptom domains. METHODS: We administered a temporal decision-making
      task, which required trial-by-trial adjustment of reaction time to maximize
      reward receipt, to 51 patients with SZ and 39 age-matched healthy control
      subjects. Task conditions were designed such that expected value (probability *
      magnitude) increased, decreased, or remained constant with increasing response
      times. Computational analyses were applied to estimate the degree to which trial
      by-trial responses are influenced by reinforcement history. RESULTS: Individuals
      with SZ showed impaired Go learning but intact NoGo learning relative to control
      subjects. These effects were most pronounced in patients with higher levels of
      negative symptoms. Uncertainty-based exploration was substantially reduced in
      individuals with SZ and selectively correlated with clinical ratings of
      anhedonia. CONCLUSIONS: Schizophrenia patients, particularly those with high
      negative symptoms, failed to speed reaction times to increase positive outcomes
      and showed reduced tendency to explore when alternative actions could lead to
      better outcomes than the status quo. Results are interpreted in the context of
      current computational, genetic, and pharmacological data supporting the roles of
      striatal and prefrontal dopamine in these processes.

PMID- 21168125
TI  - TTC12-ANKK1-DRD2 and CHRNA5-CHRNA3-CHRNB4 influence different pathways leading to
      smoking behavior from adolescence to mid-adulthood.
AB  - BACKGROUND: CHRNA5-CHRNA3-CHRNB4 and TTC12-ANKK1-DRD2 gene-clusters influence
      smoking behavior. Our aim was to test developmental changes in their effects as
      well as the interplays between them and with nongenetic factors. METHODS:
      Participants included 4762 subjects from a general population-based, prospective
      Northern Finland 1966 Birth Cohort (NFBC 1966). Smoking behavior was collected at
      age 14 and 31 years. Information on maternal smoking, socioeconomic status, and
      novelty seeking were also collected. Structural equation modeling was used to
      construct an integrative etiologic model including genetic and nongenetic
      factors. RESULTS: Several single nucleotide polymorphisms in both gene-clusters
      were significantly associated with smoking. The most significant were in CHRNA3
      (rs1051730, p = 1.1 * 10(-5)) and in TTC12 (rs10502172, p = 9.1 * 10(-6)). CHRNA3
      rs1051730[A] was more common among heavy/regular smokers than nonsmokers with
      similar effect-sizes at age 14 years (odds ratio [95% CI]: 1.27 [1.06-1.52]) and
      31 years (1.28 [1.13-1.44]). TTC12-rs10502172[G] was more common among smokers
      than nonsmokers with stronger association at 14 years (1.33 [1.11-1.60]) than 31
      years (1.14 [1.02-1.28]). In adolescence, carriers of three-four risk alleles at
      either CHRNA3-rs1051730 or TTC12-rs10502172 had almost threefold odds of smoking
      regularly than subjects with no risk alleles. TTC12-rs10502172 effect on smoking
      in adulthood was mediated by its effect on smoking in adolescence and via novelty
      seeking. Effect of CHRNA3-rs1051730 on smoking in adulthood was direct.
      CONCLUSIONS: TTC12-ANKK1-DRD2s seemed to influence smoking behavior mainly in
      adolescence, and its effect is partially mediated by personality characteristics
      promoting drug-seeking behavior. In contrast, CHRNA5-CHRNA3-CHRNB4 is involved in
      the transition toward heavy smoking in mid-adulthood and in smoking persistence.
      Factors related to familial and social disadvantages were strong independent
      predictors of smoking.

PMID- 21168126
TI  - Human microRNAs miR-22, miR-138-2, miR-148a, and miR-488 are associated with
      panic disorder and regulate several anxiety candidate genes and related pathways.
AB  - BACKGROUND: The involvement of microRNAs (miRNAs) in neuronal differentiation and
      synaptic plasticity suggests a role for miRNAs in psychiatric disorders;
      association analyses and functional approaches were used to evaluate the
      implication of miRNAs in the susceptibility for panic disorder. METHODS: Case
      control studies for 712 single-nucleotide polymorphisms (SNPs) tagging 325 human
      miRNA regions were performed in 203 Spanish patients with panic disorder and 341
      control subjects. A sample of 321 anxiety patients and 642 control subjects from
      Finland and 102 panic disorder patients and 829 control subjects from Estonia was
      used as a replica. Reporter-gene assays and miRNA overexpression experiments in
      neuroblastoma cells were used to functionally evaluate the spectrum of genes
      regulated by the associated miRNAs. RESULTS: Two SNPs associated with panic
      disorder: rs6502892 tagging miR-22 (p < .0002), and rs11763020 tagging miR-339 (p
      < .00008). Other SNPs tagging miR-138-2, miR-488, miR-491, and miR-148a regions
      associated with different panic disorder phenotypes. Replication in the north
      European sample supported several of these associations, although they did not
      pass correction for multiple testing. Functional studies revealed that miR-138-2,
      miR-148a, and miR-488 repress (30%-60%) several candidate genes for panic
      disorder--GABRA6, CCKBR and POMC, respectively--and that miR-22 regulates four
      other candidate genes: BDNF, HTR2C, MAOA, and RGS2. Transcriptome analysis of
      neuroblastoma cells transfected with miR-22 and miR-488 showed altered expression
      of a subset of predicted target genes for these miRNAs and of genes that might be
      affecting physiological pathways related to anxiety. CONCLUSIONS: This work
      represents the first report of a possible implication of miRNAs in the etiology
      of panic disorder.

PMID- 21168127
TI  - Synthesis and conformational analysis of 1,2-cis fused bicyclic alpha-d
      galactofuranosyl thiocarbamate from per-O-tert-butyldimethylsilyl-beta-d
      galactofuranosyl isothiocyanate.
AB  - Per-O-tert-butyldimethylsilyl-alpha,beta-d-galactofuranosyl isothiocyanate (4)
      was synthesized by the reaction of per-O-TBS-beta-d-galactofuranose (1) with
      KSCN, promoted by TMSI. Upon O-desilylation (1,2-dideoxy-alpha-d
      galactofuranoso)[1,2d]-1,3-oxazolidine-2-thione (6), the cis-fused bicyclic
      thiocarbamate was obtained as the only product. Conformational analysis, aided by
      molecular modelling, showed two stable twist forms ((3)T(4) and (4)T(O)) for the
      five-membered sugar ring in 6. In aqueous solution, the equilibrium favours the
      first conformation (3:1 ratio). On the other hand, this ratio decreases for less
      polar solvents.

PMID- 21168128
TI  - A fertile male patient with Kallmann syndrome and two missense mutations in the
      KAL1 gene.
AB  - OBJECTIVE: To present clinical, genetic, biochemical, and molecular findings in a
      male fertile patient with Kallmann syndrome (KS). DESIGN: Case report. SETTING:
      University medical center. PATIENT(S): A 26-year-old Chinese man.
      INTERVENTION(S): Clinical evaluation, hormone assays, gene mutation research.
      MAIN OUTCOME MEASURE(S): Endocrinologic evaluation and genetic analysis.
      RESULT(S): The patient had KS as a result of two missense mutations at exon 11 of
      KAL1 gene, 1690 G>A and 1765 G>A, a G->A transition in codons 514 and 539, which
      resulted in the replacement of lysine by glutamic acid, respectively. One of them
      is a novel mutation. CONCLUSION(S): Although loss-of-function mutations of the
      KAL1 gene is associated with the X-linked form of KS, the reproductive capacity
      remains unidentified in patients with KS with KAL1 gene mutations. Here, we
      report a male patient who presented the KS phenotype with fertility. The
      patient's sperm parameters were lower than the reference ranges; however, a son
      was born through natural conception after 12 months of marriage. Mutation
      analysis revealed two KAL1 gene mutations. The results provided further support
      for the hypothesis that patients with KS can achieve normal sexual development
      and fertility after hCG treatment, and imply that this genotype is more prevalent
      in reproductive patients with KS than in the other patients with KS and incurable
      infertility.

PMID- 21168129
TI  - Late ovarian hyperstimulation syndrome after controlled ovarian stimulation in a
      woman with systemic lupus erythematosus and lupus nephritis.
AB  - OBJECTIVE: To report a case of late ovarian hyperstimulation syndrome (OHSS) in a
      woman with lupus nephritis undergoing controlled ovarian stimulation and in vitro
      fertilization (IVF) with subsequent transfer into a gestational surrogate.
      DESIGN: A case report. SETTING: Academic reproductive medicine clinic.
      PATIENT(S): A 33-year-old woman who presented 10 days after recombinant human
      chorionic gonadotropin (hCG) injection with fatigue, abdominal pain, and
      bloating, diagnosed as OHSS. INTERVENTION(S): Patient admitted for intravenous
      fluid hydration, anticoagulation, and gonadotropin-releasing hormone (GnRH)
      antagonist therapy. MAIN OUTCOME MEASURE(S): Successful detection and management
      of severe OHSS in a patient with chronically impaired kidney function. RESULT(S):
      The patient has returned to her baseline condition, and the gestational carrier
      was noted to have a twin gestation. CONCLUSION(S): In patients with impaired
      renal function, final oocyte maturation should be triggered with a GnRH agonist
      rather than hCG.

PMID- 21168130
TI  - Vaporization of ovarian endometrioma using plasma energy: histologic findings of
      a pilot study.
AB  - In ten ovarian endometriomas of diameter exceeding 30 mm, managed by complete
      vaporization of the inner surface using plasma energy followed by cystectomy, we
      performed histologic evaluation of the depth of necrosis and the effectiveness of
      endometrial tissue ablation. We observed that plasma energy allows the ablation
      of endometrial tissue with minimal damage to the ovarian parenchyma, which
      suggests that this technique might be of particular interest for women with risk
      factors of postoperative ovarian reserve impairment, such as recurrent and
      bilateral endometriomas.

PMID- 21168131
TI  - Controlled ovarian hyperstimulation for low responders in in vitro
      fertilization/intracytoplasmic sperm injection: a low-dose flare protocol.
AB  - In this retrospective study of 652 anticipated low response women, the overall
      clinical outcomes (live birth rate and clinical pregnancy rate [PR]) of low-dose
      flare (LDF) protocol appeared lower than those of conventional down-regulation
      (DR) (LDF: 15.1% vs. DR: 20.6% and LDF: 10.3% vs. DR: 17.4%, respectively). The
      findings that LDF protocol improved the clinical outcome in older women, or when
      LDF followed an unsuccessful IVF/intracytoplasmic sperm injection (ICSI) cycle
      with DR (LDF: 19.4% vs. DR: 9.76% and LDF: 13.9% vs. DR: 4.2% respectively), need
      further evaluation through randomized trials.

PMID- 21168132
TI  - Creation of a neovagina in Rokitansky syndrome: comparison between two
      laparoscopic techniques.
AB  - OBJECTIVE: To compare Vecchietti's and Davydov's laparoscopic techniques for
      creation of a neovagina in patients with Rokitansky syndrome. DESIGN: Comparative
      retrospective study. SETTING: Tertiary referral center for the treatment of
      Rokitansky syndrome. PATIENT(S): Eighty patients with Rokitansky syndrome.
      INTERVENTION(S): Patients underwent surgical creation of a neovagina. Fifteen
      patients who underwent the Vecchietti procedure from October 2003 to December
      2004 and 30 patients who underwent the Davydov procedure from June 2005 to August
      2008 were also included from two previously published studies. Follow-up lasted
      at least 12 months. MAIN OUTCOME MEASURE(S): Intraoperative parameters and
      anatomic results were compared. Functional results were compared through the
      Female Sexual Function Index. Epithelization of the neovagina was assessed in
      both groups through vaginoscopy and Schiller's test. RESULT(S): No major
      intraoperative complications were encountered in either group. Mean (+/-SD)
      duration of surgery was 30 +/- 9.6 and 134 +/- 24 minutes in Vecchietti's and
      Davydov's approach, respectively. At 12 postoperative months, length and width of
      the neovagina in the two groups were 7.5 +/- 1.1 and 2.8 +/- 0.6 cm, and 8.5 +/-
      1.6 and 2.8 +/- 0.65, respectively. Epithelization of the neovagina at 6-month
      follow-up was 60% and 80%, respectively, and 100% in both groups at 12
      postoperative months. CONCLUSION(S): Anatomic and functional outcomes of the two
      approaches tend to be comparable at 12-month follow-up; the only significant
      difference seems to be in greater length for the neovagina obtained by Davydov's
      approach.

PMID- 21168134
TI  - Vitrification of human ovarian tissue: effect of different solutions and
      procedures.
AB  - OBJECTIVE: To test the effect of different vitrification solutions and procedures
      on the morphology of human preantral follicles. DESIGN: Pilot study. SETTING:
      Gynecology research unit in a university hospital. PATIENT(S): Ovarian biopsies
      were obtained from nine women aged 22-35 years. INTERVENTION(S): Ovarian tissue
      fragments were subjected to [1] different vitrification solutions to test their
      toxicity or [2] different vitrification methods using plastic straws, medium
      droplets, or solid-surface vitrification before in vitro culture. MAIN OUTCOME
      MEASURE(S): Number of morphologically normal follicles after toxicity testing or
      vitrification with the different treatments determined by histologic analysis.
      RESULT(S): In the toxicity tests, only VS3 showed similar results to fresh tissue
      before and after in vitro culture (fresh controls 1 and 2). In addition, this was
      the only solution able to completely vitrify. In all vitrification procedures,
      the percentage of normal follicles was lower than in controls. However, of the
      three protocols, the droplet method yielded a significantly higher proportion of
      normal follicles. CONCLUSION(S): Our experiments showed VS3 to have no
      deleterious effect on follicular morphology and to be able to completely vitrify,
      although vitrification procedures were found to affect human follicles.
      Nevertheless, the droplet method resulted in a higher percentage of
      morphologically normal follicles.

PMID- 21168135
TI  - TRACP 5b and CTX as osteological markers of delayed fracture healing.
AB  - Radiological studies are the standard method to monitor fracture healing but they
      do not allow a timely assessment of bone healing. Biochemical markers react
      rapidly to changes in bone metabolism during fracture healing and could be an
      additional tool to monitor this process. The goal of this study was to observe
      changes in serum biomarkers and evaluate the possible differences in the serum
      levels of tartrate-resistant acid phosphatase 5b (TRACP 5b), total N-terminal
      propeptide of type I collagen (PINP), bone-specific alkaline phosphatase (BAP),
      and C-terminal cross-linking telopeptide of type I collagen (CTX) in patients
      with normal and delayed fracture healing. Several serum samples were collected
      for one year after the surgical treatment of long bone fractures in 248 patients.
      From this large pool, 15 patients with atrophic nonunion were matched to 15
      patients with normal bone healing. Post-operative changes in osteological markers
      were monitored during the 1st, 2nd, 4th, 8th, 12th and 52nd weeks. The patients
      were followed both clinically and radiologically for the entire one-year duration
      of the study. In the first week, the absolute values of CTX decreased
      significantly (p=0.0164) in cases of delayed fracture healing. The relative
      values of TRACP 5b were significantly decreased at weeks 4 (p=0.0066) and 8
      (p=0.0043). BAP and PINP levels decreased in the first week followed by an
      increase, but there were no significant differences in the absolute or relative
      values during the healing process in both patient groups. For the first time, we
      have demonstrated changes in serum concentrations of TRACP 5b, PINP, BAP, and CTX
      during normal and delayed fracture healing. Characteristic changes in systemic
      TRACP 5b and CTX levels could reflect the initial process of successful fracture
      healing and may be used in clinical practice to monitor the healing process.
      Furthermore, it could be very important for determining the beneficial effects of
      additional treatments such as ultrasound or BMPs in clinical trials.

PMID- 21168136
TI  - Growth factor release in extra- and intramedullary osteosynthesis following
      tibial fracture.
AB  - INTRODUCTION: Recent studies indicate alterations of local and systemic growth
      factor level during fracture healing. As a result, osteogenic and angiogenic
      growth factors allow us to monitor fracture healing on a molecular level. We
      hypothesised that closed intramedullary (IM) reaming and nail fixation, in
      contrast to open reduction and internal plate fixation (ORIF), could exert an
      effect on the cellular elements present in the intramedullary canal, leading to
      increased release of mediators. The purpose of the study was to investigate
      whether different osteosynthesis techniques influence the released quantity of
      cytokines. PATIENTS AND METHODS: A total of 34 patients with tibia fractures
      treated with IM fixation and 19 patients treated with ORIF were included in the
      study. In addition to clinical and radiological examination, serum concentrations
      of transforming growth factor beta 1(TGF-beta1), macrophage-colony stimulating
      factor (M-CSF) and vascular endothelial growth factor (VEGF), were analysed at 1,
      2, 4, 6, 8, 12, and 24 weeks after surgery. RESULTS: Expression of TGF-beta1 and
      M-CSF was increased during the first 2 weeks of fracture healing in patients
      treated with the IM fixation technique compared with those treated by ORIF. After
      24 weeks, M-CSF levels in patients with IM fixation were clearly higher.
      Conversely, VEGF levels were higher during the first 2 weeks of fracture healing
      in patients treated by ORIF compared with IM fixation. However, these results
      were not significant. CONCLUSION: Our results show that 1 week after surgery
      neither reamed IM fixation nor ORIF of the tibia could increase the expression of
      VEGF, M-CSF and TGF-beta1 in its favour.

PMID- 21168137
TI  - Effect of the fixator stiffness on the young regenerate bone after bone
      transport: computational approach.
AB  - Bone transport is a well accepted technique for the treatment of large bony
      defects. This process is mechanically driven, where mechanical forces play a
      central role in the development of tissues within the distracted gap. One of the
      most important mechanical factors that conditions the success of bone
      regeneration during distraction osteogenesis is the fixator stiffness not only
      during the distraction phase but also during the consolidation phase. Therefore,
      the aim of the present work is to evaluate the effect of the stiffness of the
      fixator device on the interfragmentary movements and the tissue outcome during
      the consolidation phase. A previous differentiation model (Claes and Heigele,
      1999) is extended in order to take into account the different behaviors of the
      tissues in tension and compression. The numerical results that were computed
      concur with experimental findings; a stiff fixator promotes bone formation while
      the excessive motion induced by extremely flexible fixators is adverse for bony
      bridging. Experimental interfragmentary movement is similar to that computed
      numerically.

PMID- 21168138
TI  - Sedimentation field flow fractionation and flow field flow fractionation as tools
      for studying the aging effects of WO3 colloids for photoelectrochemical uses.
AB  - WO3 colloidal suspensions obtained through a simple sol-gel procedure were
      subjected to a controlled temperature aging process whose time evolution in terms
      of particle mass and size distribution was followed by sedimentation field flow
      fractionation (SdFFF) and flow field flow fractionation (FlFFF). The experiments
      performed at a temperature of 60  degrees C showed that in a few hours the
      initially transparent sol of WO3 particles, whose size was less than 25 nm,
      undergoes a progressive size increase allowing nanoparticles to reach a maximum
      equivalent spherical size of about 130 nm after 5 h. The observed shift in
      particle size distribution maxima (SdFFF), the broadening of the curves (FlFFF)
      and the SEM-TEM observations suggest a mixed mechanism of growth-aggregation of
      initial nanocrystals to form larger particles. The photoelectrochemical
      properties of thin WO3 films obtained from the aged suspensions at regular
      intervals, were tested in a biased photoelectrocatalytic cell with 1M H2SO4 under
      solar simulated irradiation. The current-voltage polarization curves recorded in
      the potential range 0-1.8 V (vs. SCE) showed a diminution of the maximum
      photocurrent from 3.7 mA cm-2 to 2.8 mA cm-2 with aging times of 1h and 5h,
      respectively. This loss of performance was mainly attributed to the reduction of
      the electroactive surface area of the sintered particles as suggested by the
      satisfactory linear correlation between the integrated photocurrent and the
      cyclic voltammetry cathodic wave area of the W(VI)->W(V) process measured in the
      dark.

PMID- 21168133
TI  - Circulating inflammatory markers in polycystic ovary syndrome: a systematic
      review and metaanalysis.
AB  - OBJECTIVE: To perform a review and metaanalysis of the studies evaluating the
      status of serum inflammatory markers in women with polycystic ovary syndrome
      (PCOS). DESIGN: Systematic review and metaanalysis of articles published in
      English before January 2010 and identified using the PubMed search engine.
      SETTING: Academic hospital. PATIENT(S): Women with PCOS and appropriate controls.
      INTERVENTION(S): Measurement of serum concentrations of inflammatory markers by
      high-sensitivity techniques. MAIN OUTCOME MEASURE(S): Metaanalyses of the mean
      difference in serum C-reactive protein (CRP), interleukin-6 (IL-6) and tumor
      necrosis factor-alpha (TNF-alpha) concentrations among patients with PCOS and
      appropriate controls, applying random-effects models to limit interstudy
      variability, and using appropriate estimates of evidence dissemination bias.
      RESULT(S): Metaanalysis of the 31 articles meeting inclusion criteria showed that
      circulating CRP was 96% higher in women with PCOS compared to controls (95%
      confidence interval, 71%-122%; z = 7.32) without evidence of dissemination bias
      (Egger's regression intercept, 0.45; 95% confidence interval, -2.30 to 3.21).
      These findings persisted after excluding five studies with mismatches in body
      mass, frequency of obesity, or both, between women with PCOS and controls.
      Metaanalyses involving 10 studies of IL-6, and nine studies of TNF-alpha revealed
      no statistically significant differences between PCOS and controls.
      CONCLUSION(S): Women with PCOS exhibit an elevation in circulating CRP that is
      independent of obesity. This finding corroborates existing molecular evidence of
      the chronic low-grade inflammation that may underpin the pathogenesis of this
      disorder.

PMID- 21168139
TI  - Global approach for the selection of high temperature comprehensive two
      dimensional gas chromatography experimental conditions and quantitative analysis
      in regards to sulfur-containing compounds in heavy petroleum cuts.
AB  - Extending the knowledge on sulfur-containing compounds is crucial for the
      petroleum industry because they contribute to atmospheric pollution by
      combustion. Most of them are concentrated in heavy petroleum cuts, such as vacuum
      gas oils (VGOs). However, the resolution of the existing analytical methods does
      not allow a quantitative speciation of S-compounds contained in VGOs. Therefore,
      a high temperature GC*GC chromatograph hyphenated to a SCD was implemented in
      this study to obtain a quantitative S-compounds speciation. Firstly, various
      thermally stable stationary phases, in particular the new ionic liquid IL59 and
      Mega Wax-HT, were investigated in 1D-GC as a way to reduce the number of columns
      sets to be used in GC*GC. Consequently, several normal and reversed
      configurations of these columns were selected and tested in GC*GC. Then, a
      decision method was applied to facilitate the choice of the best combination of
      columns. Finally, the most adapted methods led to an innovative group type
      quantification and to a quantitative distribution of heavy sulfur species
      contained in a VGO sample. These results represent a major step towards the study
      of S-compounds in heavy petroleum cuts.

PMID- 21168141
TI  - Emulsion templated open porous membranes for protein purification.
AB  - Approximately 25 cm*25 cm large sheets of crosslinked highly porous poly(glycidyl
      methacrylate-co-ethyleneglycol dimethacrylate-co-ethylhexyl methacrylate)
      membranes with an average thicknesses between 285 and 565 MUm were prepared by
      casting a high internal phase emulsion (HIPE) containing monomers onto glass
      substrates and subsequent polymerisation. Open cellular porous polyHIPE type
      membranes were obtained with large pores (cavity) sizes between 3 and 10 MUm
      while interconnecting pores were between 1 and 3 MUm. The percentage of
      ethylhexyl acrylate and ethyleneglycol dimethacrylate influenced the flexibility
      and morphology of the resulting membranes. Porous membranes were chemically
      modified with diethylamine to yield functionalised supports for ion exchange
      chromatography. Cylindrical housings were used for positioning of the membranes
      and allowing flow of the mobile phase. Pulse experiments were used to study the
      flow characteristics and a homogeneous flow through the entire area of the
      membrane was found. Bovine serum albumin was purified by a 8 ml column containing
      functional membrane in modular shape; dynamic binding capacity was measured to be
      as high as 45 mg/ml.

PMID- 21168142
TI  - Hydrophilic interaction liquid chromatography in the separation of a moderately
      lipophilic drug from its highly polar metabolites--the cardioprotectant
      dexrazoxane as a model case.
AB  - This paper presents a systematic study of the retention behavior of a model
      bisdioxopiperazine drug, dexrazoxane (DEX) and its three polar metabolites (two
      single open-ring intermediates-B and C and an EDTA-like active compound ADR-925)
      on different stationary phases intended for hydrophilic interaction liquid
      chromatography (HILIC). The main aim was to estimate advantages and limitations
      of HILIC in the simultaneous analysis of a moderately lipophilic parent drug and
      its highly polar metabolites, including positional isomers, under MS compatible
      conditions. The study involved two bare silica columns (Ascentic Express HILIC,
      Atlantis HILIC) and two stationary phases with distinct zwitterionic properties
      (Obelisc N and ZIC HILIC). The chromatographic conditions (mobile phase strength
      and pH, column temperature) were systematically modified to assess their impact
      on retention and separation of the studied compounds. It was found that the bare
      silica phases were unable to separate the positional isomers (intermediates B and
      C), whereas both columns with zwitterionic properties (Obelisc N and ZIC HILIC)
      were able to separate these structurally very similar compounds. However, only
      ZIC HILIC phase allowed appropriate separation of DEX and all its metabolites to
      a base line within a single run. A mobile phase composed of a mixture of ammonium
      formate (0.5 mM) and acetonitrile (25:75, v/v) was suggested as optimal for the
      simultaneous analysis of DEX and its metabolites on ZIC HILIC. Thereafter, HILIC
      LC-MS analysis of DEX and all its metabolites was performed for the first time to
      obtain basic data about the applicability of the suggested chromatographic
      conditions. Hence, this study demonstrates that HILIC could be a viable solution
      for the challenging analysis of moderately polar parent drug along with its
      highly polar metabolites including the ability to separate structurally very
      similar compounds, such as positional isomers.

PMID- 21168143
TI  - Fabrication of robust micro-patterned polymeric films via static breath-figure
      process and vulcanization.
AB  - Here, we present the preparation of thermally stable and solvent resistant micro
      patterned polymeric films via static breath-figure process and sequent
      vulcanization, with a commercially available triblock polymer, polystyrene-b
      polyisoprene-b-polystyrene (SIS). The vulcanized honeycomb structured SIS films
      became self-supported and resistant to a wide range of organic solvents and
      thermally stable up to 350 degrees C for 2h, an increase of more than 300K as
      compared to the uncross-linked films. This superior robustness could be
      attributed to the high degree of polyisoprene cross-linking. The versatility of
      the methodology was demonstrated by applying to another commercially available
      triblock polymer, polystyrene-b-polybutadiene-b-polystyrene (SBS). Particularly,
      hydroxy groups were introduced into SBS by hydroboration. The functionalized two
      dimensional micro-patterns feasible for site-directed grafting were created by
      the hydroxyl-containing polymers. In addition, the fixed microporous structures
      could be replicated to fabricate textured positive PDMS stamps. This simple
      technique offers new prospects in the field of micro-patterns, soft lithography
      and templates.

PMID- 21168144
TI  - Induction heating for surface triggering styrene polymerization on titanium
      modified with ATRP initiator.
AB  - Titanium and its alloys present high interests for technological applications due
      to their high corrosion resistance, mechanical properties and biocompatibility.
      In combination with these remarkable characteristics, some Ti applications
      require specific surface properties that can be imparted with suitable surface
      functionalizations of the TiO(2) oxide layer. The present work aims to study the
      surface-initiated ATR polymerization of styrene on titanium substrates, using
      grafted 11-(2-bromoisobutyrate)-undecyl-1-phosphonic acid as initiator and to
      compare the impact of two different heating ways on the efficiency of this
      polymerization: induction vs. conventional heating. The ability of the initiator
      to bind titanium substrates and act as an initiator for ATRP of styrene is
      investigated: both heating conditions led to the polymerization of styrene on
      modified titanium substrates. However, induction heating appeared to be much more
      efficient than conventional heating, leading to the formation of a thicker, much
      denser polystyrene layer than conventional heating after only 1h of
      polymerization.

PMID- 21168145
TI  - A nonverbal phoneme deletion task administered in a dynamic assessment format.
AB  - PURPOSE: The purpose of the project was to design a nonverbal dynamic assessment
      of phoneme deletion that may prove useful with individuals who demonstrate
      complex communication needs (CCN) and are unable to communicate using natural
      speech or who present with moderate-severe speech impairments. METHOD: A
      nonverbal dynamic assessment of phoneme deletion with a systematic prompting and
      scoring system was developed and compared to the same measure administered using
      a traditional "static" format. Both versions were administered to 64 typically
      developing children ranging in age from 6 to 8;5. The dynamic phoneme deletion
      task was designed so that no verbal response was required. Children were asked to
      point to pictures representing each stimulus item. The same stimulus items were
      administered to children in a traditional static format, without the use of
      pictures. For example, in the dynamic assessment task, children were asked to
      point to 1 of 4 pictures (e.g., ice) to indicate their response when asked to
      delete "m" from "mice." In the static format, children were asked to "say" the
      real word left over after deleting "m" from "mice." Correlations between phoneme
      deletion tasks and word-level reading tasks were calculated. RESULTS: Internal
      reliability for the nonverbal dynamic phoneme deletion task was alpha=.88 for the
      total sample. Correlations between the dynamic and static formats were high
      (r=.84) as were correlations between the deletion tasks and the measure of word
      level reading (dynamic; r=.54, static; r=.53). CONCLUSIONS: These preliminary
      findings suggest that the nonverbal dynamic phoneme deletion task holds promise
      for use with children for whom speech output is compromised. Implications for use
      with children who use AAC or who have significant speech impairments and
      recommendations for future research are discussed. LEARNING OUTCOMES: Readers
      will learn about a nonverbal dynamic assessment of phoneme deletion that may
      prove useful for measuring phoneme awareness for children who are unable to
      communicate using natural speech or who present with moderate-severe speech
      impairments. Readers will learn about the importance of accurate measurement of
      phoneme awareness for children with complex communication needs. Readers will
      also learn about how to develop and utilize reliable and valid measures of
      phoneme awareness for this population of children with communication impairments.

PMID- 21168146
TI  - Severe necrotizing myocarditis caused by serratia marcescens infection in an
      axolotl (Ambystoma mexicanum).
AB  - This report provides the first account of the pathological changes associated
      with infection by Serratia marcescens in an adult male axolotl. The infection
      resulted in septicaemia with severe multifocal necrotizing myocarditis. The
      latter lesion evolved to cardiac rupture, haemopericardium and death resulting
      from cardiac tamponade. This animal was exposed to higher than usual temperatures
      (24-25  degrees C) 2 weeks before the onset of disease and this may have resulted
      in immunocompromise and opportunistic bacterial infection. S. marcescens was
      isolated from the coelomic and pericardial cavity. Both isolates were identical
      and were resistant to beta-lactam antibiotics, but not to aminoglycosides or
      fluoroquinolones. The production of red prodigiosin pigment by the bacterium
      suggested an environmental origin. Overall, the clinical and histopathological
      presentation suggests that S. marcescens should be included in the list of
      aetiological agents of the 'red-leg'/bacterial dermatosepticaemia syndrome of
      amphibians.

PMID- 21168147
TI  - Endocarditis-associated brain lesions in slaughter pigs.
AB  - Left-sided valvular endocarditis (LSVE) is a common finding in slaughter pigs.
      The lesion is often associated with renal thromboembolism, but information on
      embolization to other organs is sparse. This study focuses on the presence and
      type of endocarditis-associated brain lesions (EABLs). The brains of 20 slaughter
      pigs with spontaneously arising LSVE and 11 controls were examined by sectioning
      half of a formalin-fixed brain into 4mm slices for histological examination. The
      aetiology of the endocarditis was determined by bacteriological and, in some
      cases, by fluorescence in-situ hybridization examinations. These examinations
      identified 11 cases of Streptococcus suis, six cases of Erysipelothrix
      rhusiopathiae, one Streptococcus spp. and two cases that remained aetiologically
      undetermined. One of the S. suis cases had a dual infection with S. suis in the
      aortic valve lesions and Streptococcus dysgalactiae subsp. equisimilis in the
      atrioventricular valve lesions. Renal infarcts were present in eight cases. Focal
      encephalitis was found in 12 cases, with the number of lesions ranging from one
      to 11. Most pigs had less than four microscopical lesions. Acute lesions were
      characterized by focal microabscesses without observable bacteria. Chronic
      lesions were characterized by astrocytosis and focal accumulation of mononuclear
      leucocytes. An infarct was observed in one animal. Perivascular inflammation was
      seen in 14 cases, mostly as two or three lesions, while focal leptomeningitis was
      found in eight cases. EABLs are therefore common in slaughter pigs with LSVE. The
      number of lesions per animal is small, which may explain the limited attention
      paid to this sequela of LSVE. EABLs have rarely been reported in domestic animals
      and mostly in patients with neurological signs. The frequent occurrence of EABLs
      in slaughter pigs suggests that this pathology should be investigated in other
      animal species with LSVE.

PMID- 21168148
TI  - Ablation of left atrial tachycardia with cycle length alternans after atrial
      fibrillation ablation: significance of fractionated electrogram mapping.
AB  - INTRODUCTION: Atrial tachycardia (AT) with cycle length alternans occurring after
      atrial fibrillation ablation has not been previously described. METHODS: Among 66
      patients with left AT, stable AT with 2 alternating cycles was registered in 5
      cases. Activation mapping of both alternating cycles was performed in all 5
      patients. Entrainment and fractionated electrogram mappings were also carried
      out. RESULTS: Among 10 AT cycles, activation maps suggested underlying mechanism
      of 5 cycles (50%) in 3 patients. Entrainment pacing was helpful in 2 patients
      (confirmed mechanism of 2 AT cycles). Catheter ablation successfully terminated
      AT in all 5 patients: ablation of sites with fractionated potentials in 4
      patients and mitral isthmus ablation in 1 patient. CONCLUSION: Consecutive
      activation mapping of both AT cycles is feasible for mechanism determination in
      some patients. The results of our small study suggest that fractionated
      electrogram-guided ablation might be a reasonable approach for termination of
      this type of AT.

PMID- 21168149
TI  - Coexistence of 2 types of atrial tachycardias and right ventricular outflow tract
      tachycardia.
AB  - Double tachycardia is a relatively uncommon type of tachycardia. In this report,
      we discuss a 68-year-old woman with history of frequent palpitations.
      Electrophysiologic study revealed that narrow QRS tachycardias from 2 origins and
      1 wide QRS tachycardia were induced and each of the tachycardias was induced by
      the other. We found that 2 focal atrial tachycardias and 1 ventricular
      tachycardia originated from right ventricular outflow tract. All of these
      tachycardias were successfully ablated during one session, and no recurrence
      appeared during 10 months of follow-up.

PMID- 21168150
TI  - Noninvasive estimation of organization in atrial fibrillation as a predictor of
      sinus rhythm maintenance.
AB  - Previous studies indicate that the predictive value of atrial fibrillatory rate
      in patients undergoing cardioversion of atrial fibrillation (AF) of long duration
      is limited. The present study investigates signal entropy in this setting.
      Standard 12-lead electrocardiograms (ECGs) were recorded from 66 consecutive
      patients with AF undergoing cardioversion and sample entropy estimated. Patients
      were followed for 4 weeks. At follow-up, 59% of the patients had relapsed to AF.
      The AF signal entropy of these patients before cardioversion was 0.099 +/- 0.015,
      whereas it was 0.093 +/- 0.012 among the 41% maintaining sinus rhythm (P = .02).
      As hypothesized, signal entropy was lower in patients who maintained sinus rhythm
      4 weeks after cardioversion than in those who did not. However, the overlap was
      large, making its clinical value limited.

PMID- 21168151
TI  - Preferential conduction patterns along the coronary sinus during atrial
      fibrillation in humans and their modification by pulmonary vein isolation.
AB  - INTRODUCTION: Correlation function analysis applied to endocardial electrograms
      has earlier been used for analysis of agreement between signals and direction of
      activation during atrial fibrillation (AF). This study was aimed at evaluating
      whether preferential activation patterns along the coronary sinus (CS) exist in
      patients with AF. METHODS: Twenty-seven patients (57 +/- 10 years old) admitted
      for electrophysiological (EP) study (10 patients) and/or AF ablation (17
      patients) were studied, 8 with permanent and 19 with persistent AF. Unipolar
      signals were recorded during 60 seconds from a 10-pole CS catheter during AF at
      baseline (BL) and after isolation of left and right pulmonary veins and after
      additional lines in the left atrium (LA) (End). Correlation function analysis was
      applied to signals from each pair of adjacent electrodes, and graphs of cumulated
      time delay were made to enable interpretation of direction of activation.
      RESULTS: Correlation between paired signals was highest in the distal and middle
      parts of CS and lowest in the proximal CS. In 21 patients, correlation values
      greater than 0.8 between closely spaced electrodes suggested uniform propagation
      of the fibrillatory waves. In 18 of 21 patients, preferential conduction pattern
      along CS was seen. Of those, 15 patients had left-to-right conduction, and 3 had
      right-to-left conduction. During ablation, atrial fibrillation cycle length
      increased from 184 +/- 32 milliseconds at BL to 193 +/- 39 milliseconds after
      pulmonary vein isolation and 215 +/- 39 milliseconds at the end of ablation (P =
      .03, BL vs End). Because of ablation, preferential conduction along CS changed in
      4 patients from left to right at BL to simultaneous CS activation or right to
      left. In 1 of 3 patients with simultaneous activation at BL, the direction
      changed to right to left. No direction change was observed in any of the 3
      patients with right-to-left activation at BL. CONCLUSIONS: Atrial activation
      during AF exhibits a high degree of organization in distal and middle CS.
      Preferential conduction patterns observed in most patients may indicate either
      relatively dominant stable reentry circuits in the LA or activation spread from a
      focal source. The changes in preferential conduction during ablation of AF may
      reflect modification of AF substrate and indicate persistent right atrial sources
      not affected by ablation in the LA only.

PMID- 21168152
TI  - Potocki-Lupski syndrome: a microduplication syndrome associated with
      oropharyngeal dysphagia and failure to thrive.
AB  - OBJECTIVE: Failure to thrive (FTT) is a feature of children with Potocki-Lupski
      syndrome (PTLS) [duplication 17p11.2]. This study was designed to describe the
      growth characteristics of 24 subjects with PTLS from birth through age 5 years in
      conjunction with relevant physical features and swallow function studies. STUDY
      DESIGN: We evaluated 24 individuals with PTLS who were ascertained by chromosome
      analysis and/or array comparative genome hybridization. Clinical assessments
      included review of medical records, physical examination, otolaryngological
      examination, and swallow function studies. Measures of height and weight were
      converted to Z-scores. RESULTS: The mean weight-for-age and weight-for-length Z
      scores at birth were lower (P < .01) than the reference standard and did not
      change with age. A history of poor feeding, hypotonia, and FTT were reported in
      92%, 88%, and 71%, respectively. Individuals with hypotonia had lower weight-for
      age and body mass index-for-age Z-scores (P = .01). Swallow function studies
      demonstrated at least one abnormality in all subjects. CONCLUSIONS: FTT is common
      in children with PTLS. We hypothesize that oropharyngeal dysphagia and hypotonia
      likely contribute to FTT in patients with PTLS and recommend that once a
      diagnosis is established, the individual be assessed for feeding and growth
      issues and be availed of oromotor therapy and nutritional services.

PMID- 21168153
TI  - Pediatric endo-cosmetology and the evolution of growth diagnosis and treatment.

PMID- 21168154
TI  - Pulmonary complications and chronic conditions of Down syndrome during childhood:
      an agenda for clinical care and research.

PMID- 21168155
TI  - A common variant in the PNPLA3 gene is a risk factor for non-alcoholic fatty
      liver disease in obese Taiwanese children.
AB  - OBJECTIVE: To test the hypothesis that the presence of the PNPLA3 rs738409 G
      allele would increase the susceptibility of non-alcoholic fatty liver disease
      (NAFLD) in obese Taiwanese children. STUDY DESIGN: A total of 520 obese children
      aged 6-18 years were recruited. Their PNPLA3 rs738409 genotypes-CC, CG, or GG
      were detected by the 5'-nuclease assay. The effects of the PNPLA3 rs738409 G
      allele on pediatric NAFLD were evaluated based on liver ultrasonography findings
      and mean serum alanine aminotransferase levels in these children. RESULTS: NAFLD
      was present in 19.6% of the obese children. In comparison to the subjects with CC
      alleles, the risk of NAFLD was increased by 2.96-fold (95% CI, 1.57 to 5.59, P =
      .0008) in the subjects with CG alleles and by 5.84-fold (95% CI, 2.59 to 13.16; P
      < .0001) in those with GG alleles. Variant PNPLA3 rs738409 genotypes were
      associated with increases in mean serum alanine aminotransferase level of 4.77
      IU/L (P = .0435) in subjects with CG alleles and of 10.86 IU/L (P < .0001) in
      those with GG alleles compared with subjects with CC alleles. CONCLUSIONS: The
      variant PNPLA3 rs738409 genotypes increased the risk of NAFLD in our population
      of obese Taiwanese children. The effect of the G allele on pediatric NAFLD
      followed a dominant genetic model.

PMID- 21168156
TI  - Personality disorders and cigarette smoking among adults in the United States.
AB  - INTRODUCTION: There is a paucity of empirical information pertaining to the
      association between personality disorders and cigarette smoking. The present
      study examined whether, and to what degree, personality disorders are associated
      with cigarette smoking; investigated the specificity of any observed smoking
      personality disorder association; and the role of mood/anxiety disorders,
      substance use, and nicotine dependence in those relations. METHODS: Data were
      drawn from the National Epidemiologic Survey of Alcohol and Related Conditions
      (NESARC), a nationally representative sample of 43,083 adults in the United
      States. RESULTS: Results indicated a substantial percentage of those with
      personality disorders are nicotine dependent. Interestingly, the association
      between dependent, avoidant, histrionic, schizoid and paranoid personality
      disorders as well as former dependent smoking was partially explained by co
      occurring mood/anxiety disorders, and adjusting for such clinical conditions
      appeared to generally attenuate the strength of many other associations. Finally,
      the association between personality disorders and smoking appears to differ by
      specific personality disorder, with some of the strongest relations being evident
      for antisocial personality disorder. DISCUSSION: These novel empirical findings
      are discussed in relation to the relevance of cigarette smoking among those with
      personality disorders.

PMID- 21168157
TI  - Comparison of diffusion tensor imaging and voxel-based morphometry to detect
      white matter damage in Alzheimer's disease.
AB  - Regional atrophy of gray matter (GM) in Alzheimer's disease (AD) is well known;
      however, the relationship between macroscopic and microscopic changes of cerebral
      white matter (WM) is uncertain. The aim of this study was to investigate the
      pattern of GM, WM atrophy, and microscopic WM changes in the same individuals
      with AD. All subjects (10AD and 15 healthy controls [HC]) underwent a MRI
      scanning at 1.5 T, including a 3-dimensional volumetric scan and diffusion tensor
      imaging (DTI). We performed statistical parametric mapping (SPM) with DTI to
      evaluate the patterns of the microscopic WM changes, as well as voxel-based
      morphometry (VBM) for GM and WM volume changes between patients with AD and HC.
      GM atrophy was detected, mainly in posterior regions, and WM atrophy was
      similarly distributed, but less involved on VBM analysis. Unlike WM atrophy on
      VBM analysis, microscopic WM changes were shown in the medial frontal,
      orbitofrontal, splenium of the corpus callosum, and cingulum on DTI analysis with
      SPM. We demonstrated that the pattern of macroscopic WM atrophy was similar to GM
      atrophy, while microscopic WM changes had a different pattern and distribution.
      Our findings suggest that WM atrophy may preferentially reflect the secondary
      changes of GM atrophy, while microscopic WM changes start earlier in frontal
      areas before GM and WM atrophy can be detected macroscopically.

PMID- 21168158
TI  - Arterial switch operation in children with interrupted aortic arch: long-term
      outcomes.

PMID- 21168159
TI  - Totally thoracoscopic repair of atrial septal defect without robotic assistance:
      a single-center experience.
AB  - OBJECTIVE: The recent advent of robotically assisted surgery has enabled totally
      endoscopic repair of atrial septal defects and patent foramen ovale. This study
      investigates the feasibility and safety of totally endoscopic repair of an atrial
      septal defect through small incisions on the chest without robotic assistance.
      METHODS: Forty patients (23 female patients; average age, 15.4 +/- 8.7 years; age
      range, 6-47 years) with secundum-type ASDs were selected for this study.
      Cardiopulmonary bypass was achieved peripherally. Through 3-port incisions in the
      right chest, pericardiotomy, bicaval occlusion, atriotomy, and ASD repair were
      performed by a surgeon through a thoracoscopy. RESULTS: The cardiopulmonary
      bypass and aortic crossclamp times were 56.2 +/- 21.1 and 38.3 +/- 8.6 minutes,
      respectively. The length of stay in the intensive care unit was 23.0 +/- 4.1
      hours. There were no mortalities and no major complications in this cohort.
      Patients were discharged from the hospital 4 to 6 days after the operation.
      Transesophageal echocardiographic analysis immediately after the operation and at
      30 days showed complete closure of the defect without residual shunt.
      CONCLUSIONS: Totally endoscopic atrial septal defect repair can be achieved
      without a robotically assisted surgical system. This technique is safe and
      effective and can be used as a therapeutic option for ASD.

PMID- 21168160
TI  - Management of recalcitrant bladder neck contracture after radical prostatectomy
      for prostate cancer. UroLume stent.

PMID- 21168161
TI  - Semen and the curse of cutoffs.

PMID- 21168162
TI  - Management of recalcitrant bladder neck contracture after radical prostatectomy
      for prostate cancer. Endoscopic and open surgery.

PMID- 21168163
TI  - Editorial comment.

PMID- 21168165
TI  - Sarcosine, folate metabolism and prostate cancer--is there a link?

PMID- 21168166
TI  - The dwell time of indwelling ureteral stents--the clock is ticking but when
      should we set the alarm?

PMID- 21168167
TI  - Terminology for disorders of sex development: clarity or confusion?

PMID- 21168168
TI  - Editorial comment.

PMID- 21168169
TI  - Renal surgery--is technique more important than tumor or patient characteristics
      in preserving kidney function?

PMID- 21168170
TI  - Treatment of patients with small renal masses: a survey of the American
      Urological Association.
AB  - PURPOSE: We surveyed American Urological Association members to determine factors
      that influence the treatment of patients with small renal masses. MATERIALS AND
      METHODS: In June 2009 American Urological Association members were solicited to
      complete an online survey. Respondents were asked their preferred treatment for 8
      cases and 3 index patients. In each case computerized tomographic axial and
      schematic coronal images were provided. RESULTS: A total of 759 active urologists
      with varied training backgrounds and clinical practice settings completed the
      survey. Tumor size (OR 8.4, 95% CI 7.1-10.1), tumor depth (OR 19.2, 95% CI 14.8
      25.0) and tumor location (OR 24.0, 95% CI 18.1-31.8) were markedly associated
      with preference for radical nephrectomy instead of partial nephrectomy.
      Fellowship trained urologists (OR 0.4, 95% CI 0.2-0.6) and urologists at academic
      hospitals (OR 0.6, 95% CI 0.4-0.9) were less likely to choose radical
      nephrectomy. Respondents were more likely to choose active surveillance in an
      older patient (OR 2.7, 95% CI 2.1-3.6) or in a patient with comorbidities (OR
      10.0, 95% CI 8.0-12.4). Urologists were less likely to choose active surveillance
      for a 4 vs 2 cm tumor (OR 0.18, 95% CI 0.15-0.21). Active surveillance was chosen
      more often if the tumor was perihilar vs mid kidney (OR 2.0, 95% CI 1.8-2.3) or
      polar (OR 2.1, 95% CI 1.9-2.5). CONCLUSIONS: There is considerable heterogeneity
      in the treatment of patients with clinical T1a tumors. Several factors explain
      these differences as selected treatments are independently associated with tumor,
      patient and urologist factors.

PMID- 21168171
TI  - Organic diagenesis in sediment and its impact on the adsorption of bisphenol A
      and nonylphenol onto marine sediment.
AB  - Hydrophobic organic contaminants in marine water are mostly adsorbed onto
      (partitioned into) sediment organic matter (SOM). To study the impact of SOM
      diagenesis on sediment adsorption properties, artificial sediment with rich SOM
      content was incubated for more than 120 days. The sediment was sampled every
      week, and batch sediment adsorption tests were conducted with bisphenol A (BPA)
      and nonylphenol (NP) as the model pollutants. The results show that the amount of
      organic matter loaded in the sediment decreased by nearly 80% during incubation.
      For the incubated sediment, the BPA partition coefficient, Kd, decreased whereas
      the organic normalized partition coefficient, Koc, more than doubled. The
      experiments with NP show an even greater increase in Koc. Organic matter
      diagenesis shows a profound effect on the adsorption behavior of sediment, as the
      SOM residue has an increasing affinity and partition capacity for organic
      contaminants.

PMID- 21168172
TI  - [Guideline for the management of anaphylaxis].

PMID- 21168173
TI  - Isolation, structural elucidation and immunomodulatory activity of fructans from
      aged garlic extract.
AB  - Traditionally, garlic (Allium sativum) is known to be a significant immune
      booster. Aged garlic extract (AGE) possesses superior immunomodulatory effects
      than raw garlic; these effects are attributed to the transformed organosulfur
      compounds. AGE is also known to contain fructans; the amount of fructans in AGE
      represents a small fraction (0.22%) of the total fructans in raw garlic. In order
      to evaluate the biological activity of fructans present in AGE, both high
      molecular weight (>3.5 kDa; HF) and low molecular weight (<3 kDa; LF) fructans
      were isolated. The structures of purified HF and LF from AGE determined by (1)H
      NMR and (13)C NMR spectroscopy revealed that both have (2->1) beta-D
      fructofuranosyl bonds linked to a terminal glucose at the non-reducing end and
      beta-D-fructofuranosyl branching on its backbone. Biological activity of fructans
      was assessed by immunostimulatory activity using murine lymphocytes and
      peritoneal exudate cells (source of macrophages). Both HF and LF displayed
      mitogenic activity and activation of macrophages including phagocytosis. These
      activities were comparable to that of known polysaccharide immunomodulators such
      as zymosan and mannan. This study clearly demonstrates that garlic fructans also
      contribute to the immunomodulatory properties of AGE, and is the first such study
      on the biological effects of garlic fructans.

PMID- 21168174
TI  - Friedolanostane, friedocycloartane and benzophenone constituents of the bark and
      leaves of Garcinia benthami.
AB  - Friedolanostanes, (22Z,24E)-3beta-acetoxy-9alpha-hydroxy-17,14-friedolanosta
      14,22,24-trien-26-oic acid, (22Z,24E)-3beta,9alpha-dihydroxy-17,14-friedolanosta
      14,22,24-trien-26-oic acid, (22Z,24E)-9alpha-hydroxy-3-oxo-17,14-friedolanosta
      14,22,24-trien-26-oic acid, a friedocycloartane, (22Z,24E)-3alpha-hydroxy-17,13
      friedocycloarta-12,22,24-trien-26-oic acid, and a benzophenone, benthaphenone,
      together with known compounds (22Z,24E)-3alpha,9alpha-dihydroxy-17,13
      friedolanosta-12,22,24-trien-26-oic acid, methyl (24E)-3alpha,23-dihydroxy-17,14
      friedolanosta-8,14,24-trien-26-oate, glutinol, lupeol, and stigmasterol, were
      isolated from leaves and bark of Garcinia benthami. Their structures were
      elucidated using spectroscopic techniques, mainly 1-D and 2-D NMR spectroscopy,
      and chemical correlations.

PMID- 21168175
TI  - Emerging issues in public health: a perspective on China's healthcare system.
AB  - China's expenditure on healthcare has increased dramatically over the last 20
      years, and three broad trends are seen in the associated health outcomes. First,
      limited improvements have been achieved to aggregate high-level health outcomes,
      e.g. infant mortality. Second, development of large and widening health
      inequalities associated with disparate wealth between provinces and a rural-urban
      divide. Finally, the burden of disease is shifting from predominantly
      communicable diseases to chronic diseases. Reasons for the limited gains from
      investment in healthcare are identified as: (1) increased out-of-pocket
      expenditure including a high proportion of catastrophic expenditure; (2) a
      geographical imbalance in healthcare spending, focusing on secondary and tertiary
      hospital care and greater expenditure on urban centres compared with rural
      centres; and (3) the commercialization of healthcare without adequate attention
      to cost control, which has led to escalation of prices and decreased efficiency.
      Recently, the Chinese Government has initiated widespread reform. Three key
      policy responses are to establish rural health insurance, partly funded by the
      Government (the New Rural Co-operative Medical Care System); to develop community
      health centres; and to aspire to universal basic healthcare coverage by 2020
      (Healthy China 2020).

PMID- 21168176
TI  - The challenges of healthcare reforms in China.
AB  - China is in the process of a new round of healthcare reforms. The Chinese
      Government has launched ambitious healthcare reforms aiming to achieve equitable
      access to basic health services; and to build a safe, effective, convenient and
      inexpensive healthcare system for both urban and rural residents. This paper will
      provide a brief overview of China's healthcare reforms, and describe the
      challenges and opportunities facing these reforms.

PMID- 21168177
TI  - The need for integration in health sciences sets the future direction for public
      health education.
AB  - Since the foundation of the People's Republic of China in 1949, there has been
      remarkable developments in public health in the country. These achievements are
      primarily attributed to the public health services and patriotic public health
      campaigns, although the contribution of high-technology medical applications is
      also recognized. However, along with the recent socio-economic developments and
      scientific and technological progress, medical disciplines have become more and
      more specialized, and clinical and preventive medicine have become further
      separated from each other. Conventional Chinese wisdom says 'when long divided
      they must unite, when long united they must divide'. At the onset of the new
      round of reforms of health care in China, it seems important to revisit the
      discussions on the urgency for integration of health sciences in medicine in
      China. Several issues and viewpoints on integrating medicine are discussed in
      this paper. The biopsychosocial model for health calls for broad integration.
      Primary care development in China requires integration in education and practice,
      and in treatment and prevention. Control of chronic diseases requires integrated
      and united action. Integration of traditional Chinese medicine with Western
      medicine requires creativity. The integration perspective should be instilled in
      the minds of medical students. Integration also entails integrated practice.
      After all, integration entails integrated education and practice in public health
      education. Changing the current public health education system still has a long
      way to go. True integration requires integration of concepts, policies, resources
      and measures, as well as changes in the organization of health care including
      public health, prevention and treatment. This needs to be a systematic process.
      Finally, success of integration relies on social mobilization, advocacy,
      promotion and attention of the entire society.

PMID- 21168178
TI  - Coxiella burnetii shedding and environmental contamination at lambing in two
      highly naturally-infected dairy sheep flocks after vaccination.
AB  - Abortion due to Coxiella burnetii was confirmed in the 2007/08 season in two
      naturally-infected dairy sheep flocks. Proportion of C. burnetii shedders and
      bacterial loads in vaginal mucus were high among aborted or lambed ewes, as was
      within-flock seroprevalence. Before the next reproductive season (2008/09) 75% of
      ewes and 50% of replacement lambs were vaccinated (Coxevac, CEVA Sante Animale)
      keeping the remaining as untreated controls. Compared with the previous year
      results when abortion outbreak started, a great reduction in the percentage of
      abortions, in the number of shedders and in the bacterial burden excreted by the
      ewes was found in both flocks. However, seroconversion in non-vaccinated
      yearlings from both flocks and the presence of C. burnetii DNA in bioaerosols
      taken at sheep premises at lambing indicated that infection was still active. No
      differences were observed between vaccinated and control groups in terms of
      proportion of C. burnetii shedders. These results suggest that optimal results of
      vaccination in heavily infected flocks may not be obtained in a short-term
      period.

PMID- 21168179
TI  - Effects induced by exercise on lymphocyte beta-adrenergic receptors and plasma
      catecholamine levels in performance horses.
AB  - The effect of dynamic exercise on complete blood cell count, lymphocyte beta
      adrenergic receptor and plasma catecholamine (adrenaline and noradrenaline)
      levels in horses performing different disciplines were investigated during rest
      and after exercise. Blood samples were collected from jumping horses (n=6),
      Arabian Endurance horses (n=6) and Standardbred trotters (n=6) before and
      immediately after competition. Dynamic exercise caused a significant increase in
      red blood cell count (Standardbred trotters: P=0.0012), haemoglobin concentration
      (jumping horses: P=0.001; Standardbred trotters: P=0.01), haematocrit percentage
      (Standardbred trotters: P=0.005), neutrophil percentage (jumping horses:
      P=0.0003), lymphocyte percentage (jumping horses: P=0.0003), monocyte percentage
      (Standardbred trotters: P=0.0008), lymphocyte beta-AR numbers (jumping horses:
      P=0.01; Arabian Endurance horses: P=0.016; Standardbred trotters: P=0.05), plasma
      adrenaline concentration (Standardbred trotters: P=0.0001) and plasma
      noradrenaline levels (Standardbred trotters: P=0.003). It is concluded that acute
      increases in plasma catecholamine concentrations depended on the exercise
      performed and may induce up-regulation of beta-AR in equine lymphocytes. However,
      the exact mechanism of beta-AR up-regulation still remains unclear.

PMID- 21168180
TI  - Effect of hypoxia/reoxygenation on the contractility of the isolated bovine
      digital vein.
AB  - The bovine digital vasculature contractility has been implicated in the
      development of laminitis. To investigate the effect of hypoxia/reoxygenation on
      the contractility of isolated peripheral bovine digital veins (BDVs), vessel
      rings were studied under isometric conditions and submitted to 30 min of hypoxia
      (95%N(2)-5%CO(2)) and reoxygenation (95%O(2)-5%CO(2)) conditions, respectively.
      The BDVs contracted with a high K(+) depolarizing solution, developed hypoxia
      induced relaxation, followed by an increase in tension upon reoxygenation. In
      contrast, phenylephrine-contracted BDVs displayed a rapid, sustained and
      reversible hypoxia-induced contraction. Reoxygenation caused a rapid relaxation
      in phenylephrine-contracted BDVs. The presence of the endothelium did not modify
      the hypoxia/reoxygenation effects and hypoxia-induced contraction was still
      observed in a nominal Ca(2+)-free Krebs, however, the last effect was not
      maintained over time. The hypoxia-induced contraction in an isolated peripheral
      vein may contribute to the understanding of the physiology and pathophysiology of
      superficial venous smooth muscle contractility, particularly in the alteration of
      bovine digital haemodynamics under hypoxia/reoxygenation conditions.

PMID- 21168181
TI  - Impact of urbanization and agriculture on the occurrence of bacterial pathogens
      and stx genes in coastal waterbodies of central California.
AB  - Fecal pollution enters coastal waters through multiple routes, many of which
      originate from land-based activities. Runoff from pervious and impervious land
      surfaces transports pollutants from land to sea and can cause impairment of
      coastal ocean waters. To understand how land use practices and water
      characteristics influence concentrations of fecal indicator bacteria (FIB) and
      pathogens in natural waters, fourteen coastal streams, rivers, and tidal lagoons,
      surrounded by variable land use and animal densities, were sampled every six
      weeks over two years (2008 & 2009). Fecal indicator bacteria (FIB; Escherichia
      coli and Enterococci) and Salmonella concentrations, the occurrence of
      Bacteroidales human, ruminant, and pig-specific fecal markers, E. coli O157:H7,
      and Shiga toxin (stx) genes present in E. coli, were measured. In addition,
      environmental and climatic variables (e.g., temperature, salinity, rainfall), as
      well as human and livestock population densities and land cover were quantified.
      Concentrations of FIB and Salmonella were correlated with each other, but the
      occurrence of host-specific Bacteroidales markers did not correlate with FIB or
      pathogens. FIB and Salmonella concentrations, as well as the occurrence of E.
      coli harboring stx genes, were positively associated with the fraction of the
      surrounding subwatershed that was urban, while the occurrence of E. coli O157:H7
      was positively associated with the agricultural fraction. FIB and Salmonella
      concentrations were negatively correlated to salinity and temperature, and
      positively correlated to rainfall. Areal loading rates of FIB, Salmonella and E.
      coli O157:H7 to the coastal ocean were calculated for stream and river sites and
      varied with land cover, salinity, temperature, and rainfall. Results suggest that
      FIB and pathogen concentrations are influenced, in part, by their flux from the
      land, which is exacerbated during rainfall; once waterborne, bacterial
      persistence is affected by water temperature and salinity.

PMID- 21168182
TI  - A combined approach for a better understanding of wastewater treatment plants
      operation: statistical analysis of monitoring database and sludge physico
      chemical characterization.
AB  - Biological wastewater treatment plants (WWTP) are complex systems to assess. Many
      parameters are recorded daily in WWTP to monitor and control the treatment
      process, providing huge amounts of registered data. A combined approach of
      extracting information from the WWTP databases by statistical methods and from
      the sludge physico-chemical characterization was used here for a better
      understanding of the WWTP operation. The monitored parameters were analysed by
      multivariate statistical methods: Principal Components Analysis and multiple
      partial linear regression. The WWTP operational conditions determine the sludge
      characteristics. The bacterial activity of the sludge in terms of extra-cellular
      polymeric substances (EPS) production was assessed using size exclusion
      chromatography and the internal structure of sludge flocs was observed by
      confocal laser scanning microscopy. The diagnosis of three paper mill WWTP
      enabled the identification of an important EPS production, the presence of the
      nitrification process and the presence of PO(4)(3-) nutrient in WWTP-A. These
      three main characteristics of WWTP-A were related with a systematically good
      sludge settling. In WWTP-B and C with bad settling, the bacterial activity was
      weak.

PMID- 21168183
TI  - Non-biological inhibition-based sensing (NIBS) demonstrated for the detection of
      toxic arsenic compounds.
AB  - This work demonstrates the success of a recently developed technique in chemical
      amplification, non-biological inhibition-based sensing (NIBS), for the detection
      of toxic arsenic compounds. Screening for toxic arsenic compounds is especially
      important due to their prevalence in wastewater and water sources. The detection
      method presented in this work amplifies the chemical response of toxic arsenic
      compounds by developing a sensor chemistry where the analyte inhibits, rather
      than enhances, the rate of a catalytic reaction. This technique mimics the work
      done with enzyme inhibition; however, using non-biological molecules allows for
      selective detection without the shelf-life issue associated with biological
      molecules. Using NIBS we find that we can enhance the sensitivity of the system
      by two orders of magnitude with no apparent loss in selectivity. This work
      demonstrates the versatility of NIBS, showing that the technique can be of
      general use for the detection of toxic compounds.

PMID- 21168184
TI  - A biology-based dynamic approach for the reconciliation of acute and chronic
      toxicity tests: application to Daphnia magna.
AB  - There is the need to integrate existing toxicity data in a coherent framework for
      extending their domain of applicability as well as their extrapolation potential.
      This integration would also reduce time and cost-consuming aspects of these tests
      and reduce animal usage. In this work, based on data extracted from literature,
      we have assessed the advantages that a dynamic biology-toxicant fate coupled
      model for Daphnia magna could provide when assessing toxicity data, in
      particular, the possibility to obtain from short-term (acute) toxicity test long
      term (chronic) toxicity values taking into account the inherent variability of D.
      magna populations and the multiple sources of data. The results show that this
      approach overcomes some of the limitations of existing toxicity tests and that
      the prediction errors are considerably reduced when compared with the factor from
      2 to 5 obtained using acute-to-chronic ratios.

PMID- 21168186
TI  - Anti-TNF agents for Behcet's disease: analysis of published data on 369 patients.
AB  - OBJECTIVE: Off-label use of anti-tumor necrosis factor (TNF) agents for Behcet's
      disease (BD) is increasing. We evaluated published data on their efficacy and
      safety for patients with unmet medical needs due to severe disease
      manifestations, including ocular, gastrointestinal, and central nervous system
      involvement. METHODS: Peer-reviewed articles on anti-TNF agents for BD appearing
      in Medline/PubMed through March 2010 were identified using the appropriate
      indexing terms. RESULTS: We found 88, 12, and 13 primary articles from 20
      countries on infliximab, etanercept, and adalimumab, reporting on 325, 37, and 28
      patients, respectively. All patients were inadequately controlled with, or
      intolerant to, other immunosuppressive regimens, including interferon; 20
      patients received more than 1 anti-TNF agent. In the only randomized placebo
      controlled trial, 4-week administration of etanercept was effective in
      suppressing most of the mucocutaneous manifestations. In 16 open prospective
      studies evaluating the effect of repetitive infliximab injections (174 patients
      in total, men:women = 3:1, median follow-up = 16.2 months), sustained organ
      specific, clinical responses were evident in 90%, 89%, 100%, and 91% of patients
      with resistant mucocutaneous, ocular, gastrointestinal, and central nervous
      system involvement, respectively. Combination of infliximab with azathioprine
      and/or cyclosporine-A appeared superior to monotherapy for sustained ocular
      remission. However, due to the fact that necessary data were lacking, formal
      estimation of anti-TNF treatment effect on the disease activity indexes for
      different organ involvement was not possible. CONCLUSIONS: Although more
      controlled data are needed, there is enough published experience to suggest that
      TNF blockade represents an important therapeutic advancement for patients with
      severe and resistant, or intolerant, to standard immunosuppressive regimens BD.

PMID- 21168185
TI  - Coagulation and autoimmunity in scleroderma interstitial lung disease.
AB  - OBJECTIVES: Interstitial lung disease in systemic sclerosis (SSc-ILD) is often an
      irreversible and progressive fibrosing process that now is the leading cause of
      scleroderma-related deaths. In this review we present our current understanding
      of the role played by coagulation and particularly by thrombin in autoimmune
      mediated tissue injury and fibrosis, mainly as it relates to SSc-ILD. METHODS: We
      used PubMed to search for articles published up to October 2010 for keywords
      referring to autoimmunity, coagulation, pulmonary fibrosis, and scleroderma.
      RESULTS: SSc-ILD is an autoimmune disease associated with lymphocyte activation
      and release of various cytokines and growth factors. The production of
      autoantibodies is a central feature in SSc. Activation of the coagulation cascade
      with release of thrombin is 1 of the earliest events following tissue injury.
      Thrombin contributes to autoimmune responses by activating of pathogenic Th2
      lymphocyte profile in SSc. Thrombin also modulates tissue repair responses,
      stimulates transformation of epithelial cells, endothelial cells, and fibroblasts
      into myofibroblast phenotype, and induces secretion of several pro-immune and
      profibrotic factors, which serve as antigens for pathogenic autoantibodies
      production in SSc-ILD. CONCLUSIONS: The identification of links between
      autoimmunity and coagulation would provide new insights into the pathogenesis of
      pulmonary fibrosis associated with autoimmune diseases and further acknowledge
      the importance of thrombin in the development of SSc-ILD.

PMID- 21168187
TI  - Comparison of anti-TNF treatment initiation in rheumatoid arthritis databases
      demonstrates wide country variability in patient parameters at initiation of anti
      TNF therapy.
AB  - OBJECTIVE: Characteristics of Canadian RA patients started on anti-tumor necrosis
      factor (TNF) treatment were compared with 12 other countries. METHODS: Data from
      the Optimization of HUMIRA trial (OH) were compared with Canadian real world
      studies [Ontario Biologics Research Initiative (OBRI) and the Real-Life
      Evaluation of Rheumatoid Arthritis in Canadians Receiving HUMIRA (REACH)], and to
      data from American, Australian, British, Czech, Danish, Dutch, Finnish, German,
      Italian, Norwegian, Spanish, and Swedish RA databases. Patient characteristics
      and temporal trends at initiation of anti-TNF therapy were compared between
      countries. RESULTS: Baseline Disease Activity Scores (DAS28) varied from 5.3 to
      6.6. Lower disease severity was noted in databases from countries with less
      restrictive anti-TNF coverage: Dutch [based on previous disease-modifying
      antirheumatic drugs (DMARD) use, DAS28, swollen joint count (SJC), tender joint
      count (TJC), Health Assessment Questionnaire Disability Index (HAQ-DI), Danish
      (previous DMARD use, DAS28), Norwegian (DAS28, SJC, TJC, visual analog scale
      (VAS) of global health), and Swedish (DAS28, SJC, TJC, HAQ-DI)]. RA databases
      showed lower disease scores than did OH (P < 0.05). The US databases also showed
      lower disease severity (CORRONA: previous DMARD use, SJC, TJC; National Data Bank
      for Rheumatic Diseases: HAQ, P < 0.001). The UK and Czech Republic had
      restrictive coverage and higher mean baseline DAS28 than OH (P < 0.001). Baseline
      DAS28 in the registries with published data lowered over time (British,
      Norwegian, Danish, and Swedish) but less for the British (P < 0.001).
      CONCLUSIONS: These results confirm that regional variation exists between the 13
      countries analyzed in the initiation of treatment with anti-TNF agents among RA
      patients and suggest that in some cases this variation may be increasing. In some
      countries the mean baseline disease severity declined over time and regional
      reimbursement policies and differences in physician preferences may be
      influencing initiation of anti-TNF therapy in RA.

PMID- 21168188
TI  - The Australian Rheumatology Association Database (ARAD).

PMID- 21168189
TI  - The endotheliome: a new concept in vascular biology.
AB  - As the importance of the endothelium is becoming increasingly recognised,
      additional tools are needed to assess its functions. Separate studies have looked
      at different aspects of vascular biology primarily focusing on the central role
      of the endothelium, i.e. secretion/release of molecules in the plasma,
      physiological action on other cells, and the presence of endothelial cells
      themselves in the circulation. Targeting and protecting the endothelium is a
      promising therapeutic strategy for modifying a number of disease processes but
      'ideal' methods to monitor this treatment, like many other tools for assessing
      endothelial activity, remain elusive. We suggest that a broader view of the
      endothelium is important, and with it the concept of the assessment of overall
      vascular function, which fuses different aspects of endothelial activity into a
      unifying concept. In the present document we review the current understanding of
      endothelial biology and the methods of its assessment, and hypothesise that a
      more multifactorial approach to the endothelium will be a crucial determinant of
      outcomes and treatment strategies for different diseases. This we describe as the
      'endotheliome'.

PMID- 21168190
TI  - Tissue Factor/ FVIIa prevents the extrinsic pathway of apoptosis by regulation of
      the tumor suppressor Death-Associated Protein Kinase 1 (DAPK1).
AB  - INTRODUCTION: This study determines the impact of tissue factor (TF)-signaling on
      the extrinsic pathway of apoptosis in cancer cells and propose death associated
      protein kinase-1 (DAPK1) as a novel key regulator. MATERIALS AND METHODS: In MDA
      MB-231 breast and PC3 prostate cancer cells, mRNA levels were analyzed by real
      time PCR and protein expressions were assessed by flow cytometry or western blot.
      Caspase-8 and -3 levels, cell size, and changes in nuclear morphology were
      recorded using the ArrayScan microscope and 84 apoptosis-related genes were
      screened with the RT2 ProfilerTM PCR Array. RESULTS: In serum starved MDA-MB-231
      cells, a TF/FVIIa-sensitive upregulation of apoptosis markers was recorded.
      Similarly, TRAIL-induced apoptosis was negatively regulated by TF/FVIIa (10 and
      100 nM) and TF/FVIIa/FXa but not by active-site inhibited FVIIa. FVIIa, moreover,
      decreased the transcription of DAPK1 and thereby diminished the association
      between DAPK1 and FADD in the caspase-8 activating death-inducing signaling
      complex (DISC). TF/FVIIa regulation of caspase-8 and DAPK1 was dependent on PI3
      kinase/AKT and independent of the protease activated receptors (PAR) 1 and 2.
      Despite of receptor expression and functional signaling, both PAR-agonist
      treatment and PAR-blocking antibodies in combination with FVIIa failed to
      influence the anti-apoptotic signal. CONCLUSIONS: We hereby report that TF/FVIIa
      induced signaling governs the extrinsic pathway of apoptosis by reducing the
      levels of DAPK1 in the DISC independently of PAR1 and PAR2. This implies the
      conceivable involvement of cell surface components other than the PARs and
      entails the search for TF-dependent regulators of DAPK1 transcription.

PMID- 21168191
TI  - Reg IV protein and mRNA expression in different rat organs.
AB  - The Reg IV gene has been documented in the human colon, small intestine, stomach
      and pancreas. Expression of the Reg IV in different cell types has been
      associated with regeneration, cell growth and cell survival, cell adhesion and
      resistance to apoptosis. Since the distribution of the Reg IV protein in normal
      rat tissues is unknown, the aim of this study was to reveal the expression of the
      Reg IV protein in structurally and functionally different rat organs. The
      expression of Reg IV gene was analyzed by Western blot and reverse transcription
      polymerase chain reaction. Immunohistochemistry was used to localize Reg IV
      protein. Reg IV protein was expressed in pancreas, stomach, small intestine,
      colon, brain, spleen, kidney and urinary bladder in two-month-old male Wistar
      rats. In addition, the expression of Reg IV mRNA by reverse transcription
      polymerase chain reaction was confirmed. Our study provides detailed information
      about the expression and localization of Reg IV protein in different rat organs.
      These findings provide an evidence of Reg IV expression in different rat organs,
      which may help elucidate a potential role in growth and proliferation of
      different cells like other members of the Reg family genes which act as growth
      factors in the different organs.

PMID- 21168192
TI  - Penile myofibroma occurring in a dorsal hood prepuce.
AB  - Dorsal hood prepuce is a common congenital anomaly of the penis. Neoplasms of the
      prepuce are very rarely seen in children. We present an interesting case of a
      penile myofibroma encountered during circumcision of a dorsal hood foreskin in an
      8-month-old infant.

PMID- 21168193
TI  - Arteriosclerosis related factors had no clinical significant correlation with
      resistive index in symptomatic benign prostatic hyperplasia.
AB  - OBJECTIVE: To investigate whether the resistive index (RI) in symptomatic benign
      prostatic hyperplasia (BPH) could be used as a surrogate index of the severity of
      lower urinary tract symptoms (LUTS) due to BPH, and whether arteriosclerosis
      related factors were associated with the RI in LUTS due to BPH. METHODS: From
      January 2005 to April 2008, a total of 625 men with LUTS due to BPH were
      prospectively enrolled. Patients with heart failure, liver cirrhosis, prostatic
      cancer, neurogenic bladder, acute prostatitis, acute urinary retention, urethral
      stenosis, history of transurethral resection or any drug treatment for BPH, or
      currently under drug treatment for type 2 diabetes mellitus or dyslipidemia were
      excluded. Variables analyzed included estimated smoking status, blood pressure,
      body mass index (BMI), serum fasting glucose (FBS), lipid profile (low-density
      lipoprotein-cholesterol, high density lipoprotein-cholesterol and triglyceride),
      serum prostate-specific antigen, International Prostatic Symptom Score (IPSS),
      quality of life score, maximum urinary flow rate (Q(max.)), and postvoid residual
      urine volume (PVR). We also measured total prostate volume, transition zone (TZ)
      index, and RI using transrectal ultrasonography. Correlations among parameters
      were statistically examined. RESULTS: RI was significantly correlated with IPSS,
      Q(max.), and PVR, but not with blood pressure, BMI, or FBS. On multiple
      regression analysis, RI was a significant independent variable of IPSS, TZ index,
      and PVR. CONCLUSIONS: These findings suggest that RI might represent a surrogate
      index of the severity of LUTS due to BPH, and that RI might have no clinically
      significant relationship with arteriosclerosis-related factors.

PMID- 21168194
TI  - Trends in stricture management among male Medicare beneficiaries: underuse of
      urethroplasty?
AB  - OBJECTIVES: To analyze the trends in male urethral stricture management using the
      1992-2001 Medicare claims data and to determine whether certain racial and ethnic
      groups have a disproportionate burden of urethral stricture disease. METHODS: We
      analyzed the Medicare claims for fiscal years 1992, 1995, 1998, and 2001. The
      "International Classification of Disease, 9th revision," diagnosis codes were
      used to identify men with urethral stricture. The demographic characteristics
      assessed included patient age, race, and comorbidities, as measured using the
      Charlson index. Treatments were identified using the Physician Current Procedural
      Terminology Coding System, 4th edition, procedure codes and stratified into 4
      treatment types: urethral dilation, direct vision internal urethrotomy, urethral
      stent/steroid injection, and urethroplasty. RESULTS: The overall rates of
      stricture diagnosis decreased from 10,088/100,000 population in 1992 to 6897 in
      2001 (from 1.4% to 0.9%). The stricture prevalence was greatest among black and
      Hispanic men, although the urethroplasty rates were greatest among white men.
      Direct vision internal urethrotomy was the most common treatment, followed by
      urethral dilation, urethral stent/steroid injection, and urethroplasty. The
      urethroplasty rates remained stable, but quite low (0.6%-0.8%), during the study
      period. CONCLUSIONS: The overall rates of stricture diagnosis decreased from 1992
      to 2001. Despite the poor overall efficacy of urethrotomy and urethral dilation
      relative to urethroplasty and despite the known complications of stent placement
      in this setting, the urethroplasty rates were the lowest of all treatments.
      Although we could not determine the treatment success with these data, these
      findings suggest an underuse of the most efficacious treatment of urethral
      stricture disease, urethroplasty.

PMID- 21168195
TI  - Mechanical suction: an effective and safe method to remove large and tenacious
      clots from the urinary bladder.
AB  - OBJECTIVE: To describe an alternative technique for removing tenacious and
      chronic clots by applying stronger suction pressure through the cystoscope sheath
      in patients who had failed clot evacuation using the traditional Ellik evacuator.
      METHODS: In this method, either the 25-F cystoscope sheath or 26-F resectoscope
      sheath was directly attached with the tubing from centralized suction source, and
      moderate negative pressure (up to 250 mm Hg) was applied. RESULTS: This technique
      was used in 15 adult patients with clot retention. Average duration for clot
      retention was 36.5 hours (range 22-60 hours). All patients were rendered clot
      free in an average operative period of 88 minutes (range 60-120 minutes). At the
      end of the procedure, apart from punctuate hemorrhagic spots on the bladder
      mucosa, no complications were encountered. CONCLUSIONS: Clots that are old,
      large, and tenacious can be effectively and safely evacuated by applying moderate
      suction pressure from central suction source directly through the cystoscope
      sheath.

PMID- 21168196
TI  - Hospital costs associated with adverse events in gynecological oncology.
AB  - BACKGROUND AND OBJECTIVE: Treatment for gynecological malignancies is complex and
      may cause unintended or accidental adverse events (AE). We evaluated the costs of
      hospitalization associated with those AEs among patients who had an abdominal or
      laparoscopic procedure for proven or suspected gynecological cancer at a tertiary
      gynecological cancer center in Australia. METHODS: Data on AEs were prospectively
      collected and matched with cost data (AU$ 2008) from the hospital's clinical
      costing unit and linked to demographical, clinical and histopathological data.
      Total costs were adjusted for various clinical factors and estimated using log
      transformed ordinary least squared regression. Back-transformation was achieved
      using smearing factors. From epidemiological data, we also estimated the costs of
      AEs Australia-wide and undertook scenario and probabilistic sensitivity analyses
      to investigate the potential cost impact of reducing AEs. RESULTS: A total of 369
      patients had surgical procedures of which 95 patients (26%) had at least one AE.
      Patients with AEs incurred an extra AU$12,780 on average, adjusted for age, co
      morbidities, ovarian cancer, major or minor complications, surgical complexity,
      presence of malignancy and abdominal surgery. Mean adjusted costs (95% CI) for
      patients with intra-operative, minor post-operative and major post-operative AEs
      were AU$40,746 (11,582-71,859) AU$18,459 (17,270-19,713) and AU$67,656 (5324
      131,761), respectively. Up to an estimated AU$20.6 million/year could be saved if
      the AEs were reduced by 40%. CONCLUSION: Adverse events are associated with
      significantly increased hospitalization costs and appropriate evidence-based
      interventions are justified to minimize AEs.

PMID- 21168197
TI  - Tissue-specific signatures of activating PIK3CA and RAS mutations in
      carcinosarcomas of gynecologic origin.
AB  - OBJECTIVES: Gynecologic carcinosarcoma is an aggressive malignancy that requires
      more effective treatment approaches. However, therapeutic implications regarding
      the specific gynecologic site of origin and the admixture of carcinomatous and
      sarcomatous elements that define this tumor remain uncertain. Therefore, broad
      genotyping was performed to identify tissue-specific somatic mutational profiles
      that may help direct targeted therapies in this complex neoplasia. METHODS:
      Genotyping was conducted on primary gynecologic carcinosarcomas arising from
      various disease sites (uterus, ovary, fallopian tube, vagina) and within isolated
      histological subcomponents. Nucleic acids extracted from diagnostic tissue were
      used in a genotyping platform that simultaneously queried >120 common mutations
      across 14 cancer genes. Mutational status was correlated with clinical variables
      using logistic regression and Kaplan-Meier survival estimates. RESULTS: Cancer
      gene mutations were identified in 46% of the 52 patient cohort and include TP53
      (23%), PIK3CA (19%), KRAS (15%), CTNNB1 (4%) and NRAS (2%). Mutation in a single
      gene was observed in 31% of patient samples, while synchronous mutations
      involving 2 and 3 genes were noted in 13% and 2% of samples, respectively.
      Comparative evaluation of the carcinomatous and sarcomatous elements within a
      tumor demonstrated a similar mutation signature. Mutations in PIK3CA, KRAS and
      NRAS were exclusive to tumors of uterine origin and age-adjusted Cox proportional
      hazards modeling associated advanced age, stage and TP53 mutations with decreased
      survival in the uterine subset. CONCLUSION: While carcinosarcomas across
      gynecologic disease sites are histologically similar, therapeutically relevant
      mutations in the mitogen-activated protein kinase and phosphatidylinositol 3
      kinase pathways predominated in carcinosarcomas arising in the uterus.

PMID- 21168198
TI  - A phase II study of two topotecan regimens evaluated in recurrent platinum
      sensitive ovarian, fallopian tube or primary peritoneal cancer: a Gynecologic
      Oncology Group Study (GOG 146Q).
AB  - OBJECTIVE: To evaluate the efficacy and safety of topotecan in patients with
      recurrent ovarian, primary peritoneal, and fallopian tube carcinomas. METHODS: A
      randomized phase II analysis of platinum-sensitive patients with measurable
      disease was performed independently assessing intravenous topotecan 1.25 mg/m2
      daily*5 every 21 days (regimen I) and topotecan 4.0 mg/m2/day on days 1, 8, and
      15 of a 28-day cycle (regimen II). All patients were treated until disease
      progression, unmanageable toxicity, or patient refusal. Insufficient accrual
      related to regimen I resulted in a redesign of the study as a single arm phase II
      trial assessing only regimen II. More complete efficacy data is presented for
      regimen II as enrollment on regimen I was insufficient for some analyses.
      RESULTS: A total of 81 patients were enrolled. One patient was ineligible.
      Fifteen patients received regimen I, while 65 patients were treated with regimen
      II. The response rate on regimen I (daily*5) was 27% (90% CI: 10-51%) and 12%
      (90% CI: 6-21%) on regimen II (weekly). The median PFS and OS were 4.8 and 27.8
      months, respectively, for regimen II. Grade 3/4 neutropenia rate was 93% with
      daily*5 dosing and 28% for weekly treatment. Febrile neutropenia was very low in
      both groups. CONCLUSION: The weekly regimen of topotecan appeared less active but
      resulted in less toxicity than the daily regimen in platinum-sensitive recurrent
      ovarian cancer patients.

PMID- 21168199
TI  - Clinical predictors of bevacizumab-associated gastrointestinal perforation.
AB  - OBJECTIVES: Bevacizumab is a generally well-tolerated drug, but bevacizumab
      associated gastrointestinal perforations (BAP) occur in 0 to 15% of patients with
      ovarian carcinoma. Our goal was to evaluate the clinical predictors of BAP in
      order to identify factors, which may preclude patients from receiving treatment.
      METHODS: We conducted a review of patients with recurrent epithelial ovarian
      carcinoma treated with bevacizumab between 2006 and 2009. Demographic and
      treatment data were collected for statistical analysis. RESULTS: Eighty-two
      patients were identified; perforation occurred in 8 (9.76%). Among patients with
      perforation, a significantly higher incidence of prior bowel surgeries (p=0.0008)
      and prior bowel obstruction or ileus (p<0.0001) were found compared to non
      perforated patients. The median age at onset of bevacizumab in the perforated
      group was 3 years younger (60 vs. 63 years, p=0.61). The incidence of
      thromboembolic events, GI comorbidities, number of prior chemotherapies, and body
      mass index were similar between the groups. None of the patients in the
      perforated group developed grade 3 or 4 hypertension, compared to a 32.4%
      incidence among the non-perforated patients (p=0.09). Upon multivariate analysis,
      when controlled for age greater or less than 60, prior bowel surgery,
      obstruction/ileus, and grade 3 or 4 hypertension, only the presence of
      obstruction/ileus was noted to be a significant predictor of perforation
      (p=0.04). CONCLUSIONS: Predicting BAP remains a challenge. Bowel obstruction or
      ileus appears to be associated with increased risk of BAP.

PMID- 21168200
TI  - The expression of hepatocyte growth factor (HGF) and c-Met in uterine serous
      carcinoma.
AB  - OBJECTIVE: The hepatocyte growth factor (HGF) receptor c-Met plays an important
      role in tumor dissemination by activating mitogenic signaling pathways. The goal
      of this study was to investigate immunohistochemical (IHC) staining patterns of
      HGF and c-Met in endometrioid endometrial cancer (EC) and uterine serous cancer
      (USC) and to correlate staining with patient outcomes. METHODS: A tissue
      microarray was created using tissue from patients with atrophic endometrium (AE),
      grade 1 EC, grade 3 EC, and USC. Immunohistochemistry was used to detect c-Met,
      phosphorylated c-Met (p-c-Met), and HGF expression. Differences between IHC
      staining intensity were calculated using t-tests. Correlations between staining
      and clinicopathologic variables were determined by Chi-square testing for
      categorical variables and t-tests for continuous variables. Kaplan-Meier curves
      were constructed to analyze survival in USC. RESULTS: Patients with cancer had
      more total c-Met and HGF expression than those with AE (p=0.037, p<0.001
      respectively), but no difference in p-c-Met staining. Total c-Met and HGF
      staining was significantly different between groups (p=0.042, p<0.001
      respectively). This difference was accounted for by greater c-MET expression in
      USC compared to AE (p=0.027). Depth of invasion, stage, and lymph node status
      were not significantly related to staining intensity. Patients with strong c-Met
      and HGF staining had decreased overall survival compared to patients with weaker
      staining. CONCLUSIONS: HGF and c-Met may play a role in the progression of
      endometrial cancer and should be studied further as prognostic and therapeutic
      tools.

PMID- 21168201
TI  - Breaking the diffraction barrier: super-resolution imaging of cells.
AB  - Anyone who has used a light microscope has wished that its resolution could be a
      little better. Now, after centuries of gradual improvements, fluorescence
      microscopy has made a quantum leap in its resolving power due, in large part, to
      advancements over the past several years in a new area of research called super
      resolution fluorescence microscopy. In this Primer, we explain the principles of
      various super-resolution approaches, such as STED, (S)SIM, and STORM/(F)PALM.
      Then, we describe recent applications of super-resolution microscopy in cells,
      which demonstrate how these approaches are beginning to provide new insights into
      cell biology, microbiology, and neurobiology.

PMID- 21168202
TI  - Negative school perceptions and involvement in school bullying: a universal
      relationship across 40 countries.
AB  - Cross-national analyses explore the consistency of the relationship between
      negative school experiences and involvement in bullying across 40 European and
      North American countries, using the 2006 (40 countries n = 197,502) and 2002 (12
      countries, n = 57,007) WHO-HBSC surveys. Measures include two Cumulative Negative
      School Perception (CNSP) scales, one based on 6 mandatory items (2006) and
      another including an additional 11 items (2002). Outcome measures included
      bullying perpetration, victimization and involvement as both bully and victim.
      Logistic regression analyses suggested that children with only 2-3 negative
      school perceptions, experience twice the relative odds of being involved in
      bullying as compared with children with no negative school perceptions. Odds
      Ratios (p < 0.001) increase in a graded fashion according to the CNSP, from about
      2.2 to over 8.0. Similar consistent effects are found across gender and almost
      all countries. Further research should focus on the mechanisms and social context
      of these relationships.

PMID- 21168203
TI  - The white plague returns to London--with a vengeance.

PMID- 21168204
TI  - Lifelong reporter gene imaging in the lungs of mice following polyethyleneimine
      mediated sleeping-beauty transposon delivery.
AB  - Polyethyleneimine (PEI) is a cationic polymer that is effective in gene delivery
      in vivo. Plasmid DNA incorporating the Sleeping-Beauty (SB) transposon has been
      shown to induce long-term transgene expression in mouse lungs after PEI-mediated
      delivery. In the current report, we followed the reporter gene expression
      mediated by PEI/SB delivery in lungs of mice using the non-invasive
      bioluminescent imaging (BLI) technology. After delivery, the reporter gene signal
      showed a rapid decay in the first two weeks to a nearly undetectable level, but
      then the signal augmented gradually in the following weeks and finally reached a
      stable level that maintained until the natural death of animals. The
      stabilization of transgene expression is associated with the multiplication of a
      small number of PEI/SB-labeled alveolar cells, which proliferated both under
      normal conditions and in response to acute local injury for epithelia repair, and
      may play a role in long-term homeostatic maintenance in alveoli. The data
      presented here suggests that systemic delivery of PEI/SB induces stable
      transfection specifically in a small population of alveolar progenitor cells. The
      technique provides a promising platform for future research in distal lung
      biology and tissue regenerative therapy.

PMID- 21168205
TI  - Effects of calcium, magnesium, low-dose aspirin and low-molecular-weight heparin
      on the release of PP13 from placental explants.
AB  - BACKGROUND: Preeclampsia is one of the leading causes for maternal and fetal
      morbidity. Attempts to prevent preeclampsia have already been made using low-dose
      aspirin, low-molecular-weight heparin (LMWH), and calcium supplementation.
      Magnesium sulphate is used at the time of disease to prevent eclampsia. Here we
      investigated the effect of these agents on PP13 release from placental explants.
      METHODS: Placentas harvested after C-section of term or preterm control and
      preeclampsia cases or first trimester terminations were used to obtain explants.
      Explants were incubated for 24h with/without respective agents, harvested,
      weighed and subjected to PP13 determination in the culture medium and the
      explant. LDH was used to determine viability. Dose response curves were obtained
      for each drug. P < 0.05 was considered significant. RESULTS: Exposure to
      magnesium (0.7-7g/day) slightly decreased PP13 release from controls, and
      slightly increased it in preeclampsia and first trimester termination. Calcium
      (0. 3-6g/day) showed a tendency to decrease the release in control and
      preeclampsia, whereas in first trimester release was increased in a bell-shaped
      manner. Aspirin (0-250 mg/day) tended to decrease the release in controls but
      increased it in a bell-shaped manner in first trimester and preeclampsia. LMWH
      showed no effect from 0 to 80 mg/day in controls but tended to decrease PP13
      release in preeclampsia and first trimester. CONCLUSION: This data might point to
      a beneficial effect of aspirin and calcium supplementation in the first trimester
      of pregnancy and aspirin at the time of disease, although the interaction with
      the maternal system still needs to be elucidated.

PMID- 21168206
TI  - Angiotensin II induces complex fractionated electrogram in a cultured atrial
      myocyte monolayer mediated by calcium and sodium-calcium exchanger.
AB  - Angiotensin II (AngII) has been implicated in the mechanism of atrial
      fibrillation (AF). There may be calcium-dependent pro-fibrillatory effect of
      AngII on atrial myocytes. We used cultured confluent HL-1 atrial myocyte
      monolayer with spontaneously propagated depolarization to study direct pro
      fibrillatory effect of AngII and its molecular mechanism. AngII stimulation
      induced fibrillatory-like complex electrogram and calcium wave propagation. AngII
      shortened action potential duration and augmented calcium transient, thus
      increasing electrochemical gradient of forward-mode sodium-calcium exchanger
      (NCX) current and induced frequent irregular afterdepolarizations. AngII
      increased expression of sodium-calcium exchanger (NCX), further increasing
      calcium-membrane voltage coupling gain. The fibrillatory effect of AngII was
      attenuated by NCX blocker SEA0400 and NCX siRNA knockdown. AngII increased
      expression of L-type calcium channel and augmented calcium transient through PKC
      and CREB. The fibrillatory effect of AngII was also attenuated by PKC inhibitor
      chelerythrine and dominant negative form of CREB. In conclusions, AngII itself
      may electrically contribute to the mechanism of AF through increasing NCX
      expression and augmenting calcium transient, which is PKC and CREB dependent.
      Specific genetic knockdown of NCX attenuated calcium mediated afterdepolarization
      and complex electrogram.

PMID- 21168207
TI  - Aberrant expression of CKLF-like MARVEL transmembrane member 5 (CMTM5) by
      promoter methylation in myeloid leukemia.
AB  - CMTM5 has been shown to exhibit tumor suppressor activities, however, its role in
      leukemia is unclear. Herein we firstly reported the expression and function of
      CMTM5 in myeloid leukemia. CMTM5 was down-regulated, or undetectable, in leukemia
      cell lines and bone marrow cells from leukemia patients with promoter
      methylation. Ectopic expression of CMTM5-v1 strongly inhibited the proliferation
      of K562 and MEG-01 cells. In addition, significant negative correlations were
      observed between CMTM5 and three leukemia-specific fusion genes (AML1-ETO, PML
      RARalpha and BCR/ABL1). CMTM5 expression was up-regulated in patients who had
      undergone treatment. Therefore, CMTM5 may be involved in the pathomechanism of
      myeloid leukemias.

PMID- 21168208
TI  - Simultaneous acute myeloid leukaemia and de novo acute hepatitis B: a novel
      management strategy.

PMID- 21168209
TI  - t(9;11)(p22;p15) [NUP98/PSIP1] is a poor prognostic marker associated with de
      novo acute myeloid leukaemia expressing both mature and immature surface
      antigens.

PMID- 21168210
TI  - Concentration of polychlorinated biphenyls and organochlorine pesticides in some
      edible fish species from the Shadegan Marshes (Iran).
AB  - Concentrations of polychlorinated biphenyls (PCBs), and organochlorine pesticides
      (OCPs), such as dichlorodiphenyltrichloroethane (DDT) and analogs,
      hexachlorocyclohexanes (HCHs) and hexachlorobenzene (HCB), were determined in 8
      fish species collected during October and November 2007 from the largest Iranian
      wetland, the Shadegan Marshes. Fishes were selected on the basis of their
      importance in the local diet and feeding behavior. In all samples, OCPs were
      found in higher concentrations than PCBs. Common carp (Cyprinus carpio) had the
      highest OCs (1680 ng/g lipid wt.), with DDTs being most prevalent and p,p'-DDE
      contributing by 53-88% to the total DDTs. In all samples, OCs were found in order
      of DDTs>HCHs>PCBs>HCB. The highest concentration of HCHs was found in common carp
      (410+/-180 ng/g lipid wt.) and alpha-HCH was the predominant compound among HCH
      isomers (range 70-90%, mean 82%) in all species. All samples contained PCBs and
      CB 28 (37%) and CB 52 (26%) were the most frequently occurring congeners. common
      barbel (Barbus barbulus) (70+/-17 ng/g lipid wt.) exhibited the highest
      concentrations of HCB. OC levels in fish were relatively low, but the levels of
      several OCs in some of our specimens exceed the guidelines for food safety issued
      by the European Union (EU) and US Food and Drug Administration (FDA).

PMID- 21168211
TI  - Evaluability Assessment of an immunization improvement strategy in rural Burkina
      Faso: intervention theory versus reality, information need and evaluations.
AB  - An innovative immunization improvement strategy was proposed by the CRSN (Centre
      de Recherche en Sante de Nouna) to improve the low coverage rate for children
      aged 0-11 months in the health district of Nouna in Burkina Faso. This article
      reports on the Evaluability Assessment (EA) study that aimed to orient decisions
      for its evaluation in close relationship with the information needs of the
      stakeholders. Various methods were used, including document reviews, individual
      interviews, focus group discussions, meetings, literature reviews and site
      visits. A description of the intervention theory and philosophy is provided with
      its logic models and its reality documented. Lessons on the procedure include the
      importance of the position of the evaluability assessor, the value of replicating
      some steps of the assessment and the relationships between EA and process
      evaluation. The evaluability study concludes that the intervention had some
      evaluable components. To satisfy the stakeholders' needs, the initially planned
      community randomized controlled trial can be maintained and complemented with a
      process evaluation. There is a need to provide sufficient information on the cost
      of the intervention. This will inform decision makers on the possibility of
      replicating the intervention in other contexts.

PMID- 21168212
TI  - Humanitarian action in developing countries: who evaluates who?
AB  - Humanitarian NGOs and intergovernmental organisations are usually assessed by
      their funders, not their beneficiaries. In most cases, their evaluation relies on
      interviews with "professionals", neglects field surveys, does not use opinion
      polls and seldom tries to assess the socioeconomic impact of relief. Moreover, it
      is commissioned by stakeholders at the risk of being judge and party. Such a
      system brings several conflicts of interest: (1) it needs to be approved by those
      who are evaluated and so does not deal with "bad eggs" that refuse to be
      investigated; (2) it produces biased analysis, does not name names and passes
      over fundamental issues; (3) it is very formal and technocratic, if not
      meaningless; (4) it does not help to learn from past mistakes. Hence this article
      proposes a framework to develop third party evaluations. It is suggested that, to
      be really independent, evaluation should neither be paid or commissioned by
      stakeholders, i.e. NGOs and institutional funders. To facilitate learning, its
      methodology and its results must also be available to the general public. To be
      accepted by those who are evaluated, finally, it should highlight the
      difficulties, explain the political context, acknowledge its subjectivity,
      recognize its limits, focus on processes more than results and develop
      qualitative analysis out of quantitative indicators.

PMID- 21168214
TI  - Approaches and challenges in evaluating measures taken against right-wing
      extremism.
AB  - Right-wing extremism has reemerged on the political agenda in Switzerland over
      the last decade, much as in other European states. Most of the time, right-wing
      extremism remains latent. However, as soon as a constituency is confronted with
      manifest right-wing incidents (right-wing extremist group meetings, racist
      assaults or violence against individuals and groups), the issue reappears in the
      political sphere. The countermeasures available to governments frequently remain
      unclear: empirically based evidence on the effectiveness of specific measures is
      often simply lacking. In this article we argue that this inadequacy is mostly due
      to the specific characteristics of the particular conditions of conflict and
      violence that are associated with the phenomenon of 'right-wing extremism'. These
      conditions include an often only insufficiently clarified understanding of the
      phenomenon of 'right-wing extremism' as well as a highly sensitive political,
      social and legal context for countermeasures. Furthermore, the effectiveness of
      countermeasures is typically strongly dependent on the actors involved as well as
      their actions and interactions. Implementation is therefore often unique and, as
      a consequence, difficult to replicate. We will address these specific challenges
      for evaluation under such conditions in seven case studies. Each case study
      includes an evaluation of a measure that has been taken against phenomena of
      right-wing extremism in Switzerland on the federal, state or community level. The
      case studies show that certain challenges for evaluation can be met by adopting
      an adequate evaluation design. Other aspects require further investigation and
      may not be adequately addressed through the evaluation of countermeasures.

PMID- 21168213
TI  - Team factors that predict to sustainability indicators for community-based
      prevention teams.
AB  - Because they often set out with a guarantee of only short-term funding, many
      community partnerships will face a threat to their sustainability almost as soon
      as the first money runs out. Research into the factors that enable some
      coalitions and partnerships to meet the challenge when others fail is limited.
      This study begins to fill this gap in our understanding by examining influences
      on the process of sustainability planning in the context of a collaborative
      partnership focused on youth development. We report on a longitudinal examination
      of the quality of planning and attitudes underpinning the sustainability of
      PROSPER community prevention teams whose members implement evidence-based
      programs designed to support positive youth development and reduce early
      substance use and other problem behaviors. The current research concentrates on a
      particular dimension of partnership effectiveness to establish whether
      perceptions about team functioning in play at 6 and 18 months predict the quality
      of sustainability planning at 36 and 48 months. How well teams functioned in the
      early stages was found to be strongly related to the quality of their later
      preparations for sustainability. Recruitment and integration of new team members,
      and the encouragement they subsequently received were also found to be key
      factors. The results strengthen the argument for providing technical assistance
      to meet the needs of those who promote prevention partnerships, and they provide
      longitudinal empirical data to support the hypotheses of other researchers who
      have similarly found a correlation between effective sustainability and early
      planning and support.

PMID- 21168215
TI  - War outside, ceasefire inside: An analysis of the performance appraisal system of
      a public hospital in a zone of conflict.
AB  - Our study examines the use of the performance appraisal system at Hebron Public
      Hospital (Palestine) during the second intifada, started in 2000. The aim of the
      article is to shed light on the reasons behind the use of performance appraisal
      systems in organizations operating in zones of conflicts, an area relatively
      neglected by HR scholars. To create the theoretical fundament we draw on
      mainstream literature on performance appraisal, contextualizing it to the Middle
      Eastern context. From the literature analysis, we identify five guiding logics
      for the implementation and use of performance appraisal systems (Appendix A). We
      use a multi-method approach, qualitative and quantitative, to analyze the
      longitudinal performance evaluation data over the period 2000-2002 for about 250
      individuals. These data are complemented with interviews and observations in the
      field. Our analysis shows that the trends evidenced in the quantitative analysis
      are similar to trends evident in Western contexts. However, these trends were not
      the consequence of the same five Western logics found in the literature. The
      qualitative study allows us to identify two additional logics for making sense of
      the performance appraisal system at Hebron Public Hospital: the need to find
      peace within the organization (organizational peacefulness logic); and the need
      to maintain order through the acceptance of the status quo (dominance logic).
      These results allow us to draw conclusions for theory and practice of HR
      management and to identify useful criteria for doing research in areas of
      conflicts.

PMID- 21168216
TI  - Message and price components of Family Caps: experimental evidence from New
      Jersey.
AB  - In this paper, we examine the relative efficacy of two mechanisms--price
      consideration and the message of social responsibility--in accounting for Family
      Cap effects on fertility behavior. The Family Cap is a component of welfare
      reform policy that denies additional cash benefits to children born 10 or more
      months after a woman entered the welfare rolls. We use data from the New Jersey
      Family Development Program (FDP) evaluation that employed a classical
      experimental design. We find that fertility behaviors are influenced by both
      Family Cap price and message mechanisms but that these effects are conditioned by
      welfare recipients' time on welfare and race. Black women who have longer stays
      on welfare are more likely to be influenced by price while women with shorter
      stays are influenced by both price and the social message. We believe our results
      have implications not only for future public welfare policy initiatives but for
      any social policies that attempt to influence behavior directly, through
      individual rewards and punishments, and indirectly through the activation of
      social or community pressures.

PMID- 21168217
TI  - Novel brominated flame retardants: a review of their analysis, environmental fate
      and behaviour.
AB  - This review summarises current knowledge about production volumes, physico
      chemical properties, analysis, environmental occurrence, fate and behaviour and
      human exposure to the "novel" brominated flame retardants (NBFRs). We define the
      term NBFRs as relating to BFRs which are new to the market or newly/recently
      observed in the environment. Restrictions and bans on the use of some
      polybrominated diphenyl ether (PBDE) formulations, in many jurisdictions, have
      created a market for the use of NBFRs. To date, most data on NBFRs have arisen as
      additional information generated by research designed principally to study more
      "traditional" BFRs, such as PBDEs. This has led to a wide variety of analytical
      approaches for sample extraction, extract purification and instrumental analysis
      of NBFRs. An overview of environmental occurrence in abiotic matrices, aquatic
      biota, terrestrial biota and birds is presented. Evidence concerning the
      metabolism and absorption of different NBFRs is reviewed. Human exposure to NBFRs
      via different exposure pathways is discussed, and research gaps related to
      analysis, environmental sources, fate, and behaviour and human exposure are
      identified.

PMID- 21168218
TI  - Influence of fish size and sex on mercury/PCB concentration: importance for fish
      consumption advisories.
AB  - Fish advisories for polychlorinated biphenyls (total-PCBs) and mercury are often
      given on a length-specific basis and fish sex is usually not considered. The
      relationship between concentration and length is well established for mercury,
      however its suitability for total-PCBs and the influence of sex over the large
      scale covered by most monitoring programs is not well known. Here we use what is
      perhaps the largest consistent sport fish contaminant dataset to evaluate the
      relationship between total-PCB/mercury and length and sex. We evaluated seven of
      the most commonly consumed fishes from the Canadian Great Lakes and two Ontario
      (Canada) inland lakes. For mercury, the relationship between concentration and
      length was significant (p<0.05) in most fish species and locations. For total
      PCB, this relationship was also generally significant in Chinook salmon and lake
      trout, which are the species with the most advisories for this compound. In
      contrast, significant relationships were found less often for whitefish, northern
      pike, smallmouth bass, walleye, and especially yellow perch. However, mercury
      usually drives fish consumption advisories for these species. Overall, our
      results support the protocol of issuing contaminant advice on a length-specific
      basis in fish monitoring programs with reasonable confidence when at least a
      moderate number of samples over the natural size range of a species are included
      in the analysis. Sex differences were common for walleye (males>females, p<0.05)
      but not other species, suggesting that an equal number of male and female walleye
      should be used in deriving fish advisories for walleye.

PMID- 21168219
TI  - Gene therapy with CCL2 (MCP-1) mutant protects CVB3-induced myocarditis by
      compromising Th1 polarization.
AB  - Viral myocarditis, which is most prevalently caused by Coxsackievirus B3 (CVB3)
      infection, affects about 5-20% of the world population and lacks efficient
      treatments. We previously reported that monocyte chemotactic protein-1 (MCP-1,
      CCL2) was significantly induced during CVB3 infection and greatly contributed to
      the myocardic inflammation and injury. Herein a CCL2 mutant with removed
      chemotactic activity was administrated and its therapeutic effect on CVB3-induced
      myocarditis was explored. A dominant negative CCL2 mutant, lacking the N-terminal
      amino acids 2-8 (CCL2(Delta2-8)), was genetically constructed and intramuscularly
      injected into BALB/c mice after CVB3 infection, severity of myocarditis was
      evaluated by weight loss, survival rate, serological indices and pathological
      observation. Systemic and local Th1/Th2 cytokine profiles were also assessed.
      Mice receiving pCCL2(Delta2-8) exhibited a profound attenuation of myocarditis
      compared to pcDNA3.1 or non-treated mice, as evidenced by invariant body weight,
      decreased serum CK-MB level, reduced myocardial inflammatory infiltration and
      increased survival. This effect was not attributable to the efficient viral
      clearance, but associated with weakened Th1 immune responses, as evidenced by
      significantly reduced CD4(+)IFN-gamma(+) T cell frequency and Th1 cytokine level
      systemically and locally. Strategy of blocking in vivo CCL2 activity could
      effectively alleviate the severity of CVB3-induced myocarditis and may present an
      alternative therapeutic approach against viral myocarditis.

PMID- 21168220
TI  - SOCS3 suppresses the expression of IL-4 cytokine by inhibiting the
      phosphorylation of c-Jun through the ERK signaling pathway in rat mast cell line
      RBL-2H3.
AB  - SOCS3 is well known to negatively regulate various cytokine-mediated signaling
      responses, but its direct role in the expression of specific cytokines has not
      been clearly elucidated. To understand the role of SOCS3 in the expression of IL
      4, one of the key Th2 cytokines, RBL-2H3 cells (a rat mast cell line) were
      engineered to express SOCS3 constitutively at a high level or at a lower level
      using shRNA. In RBL-2H3 cells stably expressing SOCS3, the RNA and protein levels
      of IL-4 were significantly decreased, while it was opposite in RBL-2H3 cells
      containing shRNA for SOCS3. Overexpression of SOCS3 was found to reduce the level
      of calcium ionophore-induced phosphorylation of ERK1/2 and c-Jun transcription
      factor. Consistent with this data, knockdown of SOCS3 increased the level of
      phosphorylated ERK1 and ERK2. Taken together, SOCS3 appears to play an important
      role as a negative feedback inhibitor in the expression of IL-4 by inhibiting
      serine phosphorylation of c-Jun via the ERK signaling pathway.

PMID- 21168221
TI  - Human platelet FcgammaRIIA and phagocytes in immune-complex clearance.
AB  - In addition to their primary role in hemostasis and wound healing, platelets play
      important roles in a multitude of physiological functions including immune and
      inflammatory responses. We present data that platelets, by virtue of their
      expression of the human specific FcgammaR, FcgammaRIIA, bind IgG complexes in
      vivo and that circulating phagocytes from healthy individuals internalize
      platelets in vivo. Human platelets, as a consequence of their expression of
      FcgammaRIIA, may thus, contribute to the clearance of IgG-containing complexes
      from the circulation.

PMID- 21168223
TI  - Risk factors for intraoperative floppy iris syndrome: a meta-analysis.
AB  - PURPOSE: To evaluate risk factors (hypertension, diabetes mellitus, and current
      tamsulosin, alfuzosin, terazosin, or doxazosin use) for intraoperative floppy
      iris syndrome (IFIS) in patients undergoing phacoemulsification cataract surgery.
      DESIGN: Systematic review and meta-analysis of the literature. PARTICIPANTS:
      Seventeen eligible studies (17 588 eyes) examining the association between IFIS
      and risk factors. METHODS: Pertinent publications were identified through a
      systematic search of PubMed. All references of relevant reviews and eligible
      articles were also screened. Language restrictions were not used, and data were
      extracted from each eligible study by 2 investigators working independently. For
      medications, 2 separate analyses were performed: an analysis using a dichotomous
      criterion (use/non-use of the examined agent) and an alternative analysis
      performing comparisons with patients not receiving any alpha(1)-blocker. The
      fixed-effects model (Mantel-Haenszel method) or the random-effects (DerSimonian
      Laird) model was appropriately used to calculate the pooled odds ratio (OR).
      Publication bias was appropriately assessed. MAIN OUTCOME MEASURES: Pooled OR for
      the incidence of IFIS. RESULTS: The pooled OR for IFIS after tamsulosin use was
      approximately 40-fold greater (or 16.5 at the alternative analysis) than that
      after alfuzosin use, that is, the second alpha(1)-blocker in order of effect
      size. Alfuzosin and terazosin were also associated with IFIS with comparable ORs;
      the effect of doxazosin reached formal statistical significance at the
      alternative analysis. Intraoperative floppy iris syndrome was positively
      associated with hypertension (pooled OR = 2.2, 95% confidence interval [CI], 1.2
      4.2, fixed effects) but not with diabetes mellitus (pooled OR = 1.3, 95% CI, 0.7
      2.2, fixed effects). CONCLUSIONS: This meta-analysis has highlighted a hierarchy
      concerning the role of alpha(1)-blockers in IFIS, indicating an extremely
      sizeable effect size of tamsulosin; this may entail important physiologic
      implications. Alfuzosin, terazosin, and doxazosin presented with comparable
      effect sizes. Hypertension, but not diabetes mellitus, emerged as a risk factor
      for IFIS.

PMID- 21168222
TI  - Is diabetic retinopathy related to subclinical cardiovascular disease?
AB  - OBJECTIVE: Persons with diabetic retinopathy (DR) have an increased risk of
      clinical cardiovascular events. This study aimed to determine whether DR is
      associated with a range of measures of subclinical cardiovascular disease (CVD)
      in persons without clinical CVD. DESIGN: Population-based, cross-sectional
      epidemiologic study. PARTICIPANTS: Nine hundred twenty-seven persons with
      diabetes without clinical CVD in the Multi-Ethnic Study of Atherosclerosis.
      METHODS: Diabetic retinopathy was ascertained from retinal photographs according
      to modification of the Airlie House Classification system. Vision-threatening DR
      (VTDR) was defined as severe nonproliferative DR, proliferative DR, or clinically
      significant macular edema. Subclinical CVD measures were assessed and defined as
      follows: high coronary artery calcium (CAC) score, defined as CAC score of 400 or
      more; low ankle-brachial index (ABI), defined as ABI of less than 0.9; high ABI,
      defined as ABI of 1.4 or more; high carotid intima-media thickness (IMT), defined
      as highest 25% of IMT; and carotid stenosis, defined as more than 25% stenosis or
      presence of carotid plaque. MAIN OUTCOME MEASURES: Associations between DR and
      subclinical CVD measures. RESULTS: The prevalence of DR and VTDR in this sample
      was 30.0% and 7.2%, respectively, and VTDR was associated with a high CAC score
      (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.15-4.73), low ABI (OR,
      2.54; 95% CI, 1.08-5.99), and high ABI (OR, 12.6; 95% CI, 1.14-140.6) after
      adjusting for risk factors including hemoglobin A1c level and duration of
      diabetes. The association between VTDR and high CAC score remained significant
      after further adjustment for hypoglycemic, antihypertensive, and cholesterol
      lowering medications. Diabetic retinopathy was not significantly associated with
      measures of carotid artery disease. CONCLUSIONS: In persons with diabetes without
      a history of clinical CVD, the presence of advanced-stage DR is associated with
      subclinical coronary artery disease. These findings emphasize the need to be
      careful about the use of anti-vascular endothelial growth factor for the
      treatment of DR.

PMID- 21168224
TI  - Retinoic acid induced 1 gene and clinical subtypes of schizophrenia: an
      association study.

PMID- 21168225
TI  - Trends in the indications for pediatric tonsillectomy or adenotonsillectomy.
AB  - OBJECTIVE: To report trends in the indications for pediatric tonsillectomy or
      adenotonsillectomy. METHODS: To identify current indications, (1) a retrospective
      chart review analyzed all indications for procedures performed by a pediatric
      otolaryngologist on patients aged 0-3, 4-10, or 11-18 years, and (2) a cross
      sectional survey to members of the American Society of Pediatric Otolaryngology
      asked for approximate percentages of children in the same age groups receiving
      procedures for obstruction, infection, or another indication. To assess changing
      indications over time, (3) a literature review was performed. RESULTS: (1) Chart
      review: 302 patients aged 5 months to 18 years (average: 6.34; median: 6) were
      analyzed. For the 0-3-year age group, obstruction was an indication in 100.0% of
      cases, and infection in 2.6%. For the 4-10-year age group: 91.9% and 13.4%,
      respectively. For the 11-18-year age group: 84.6% and 33.3%. (2) SURVEY: 120
      surveys were returned (40% response rate), and 63 surveys were appropriate for
      analysis (21% completion rate). For the 0-3-year age group, obstruction was the
      primary indication in 91.8% of procedures and infection in 7.5%. For the 4-10
      year age group: 73.2% and 25.3%, respectively. For the 11-18-year age group:
      43.0% and 54.2%. (3) LITERATURE REVIEW: 11 articles consistently illustrated a
      rise in obstruction and a decline in infection as an indication since 1978.
      CONCLUSIONS: Obstruction has become a more prominent indication than infection
      for pediatric tonsillectomy or adenotonsillectomy in children, especially younger
      children. Infection becomes a more prominent indication as age increases. Data
      may not be absolutely reflective of all pediatric otolaryngologists or other
      otolaryngologists that treat children. Comparing studies is difficult owing to
      the variety of surgical procedures focused upon and terms used to define
      indications.

PMID- 21168227
TI  - Cardiac magnetic resonance imaging of mucopolysaccharidosis type II
      cardiomyopathy.

PMID- 21168228
TI  - Biology of mitral valve prolapse: the harvest is big, but the workers are few.
AB  - Mitral valve prolapse (MVP) represents a common degenerative disease, often
      requiring surgery. If untreated, MVP with considerable valve incompetence can
      lead to cardiovascular and systemic complications causing substantial morbidity
      and mortality. In contrast with the wide knowledge concerning clinical and
      physiological features, currently available data regarding its molecular bases
      are very limited. We review current knowledge concerning MVP biological
      mechanisms, focusing on specific aspects of haemostasis, platelet function,
      oxidative stress, extracellular matrix remodeling and genomics. In particular,
      available evidence supports the role played by tissue remodeling processes in
      determining MVP onset and progression. Moreover, even if a consistent although
      controversial perturbation of haemostatic system and alterations of the oxidative
      stress equilibrium have been proposed to influence disease development, it is
      unknown whether these changes precede or follow MVP occurrence. Consequently, the
      complete knowledge of all the biochemical pathways involved are far from
      complete. In addition, changes in the regulation pattern of adrenergic and renin
      angiotensin-aldosterone systems have been described in MVP syndrome, a condition
      characterized by the association of MVP with other peculiar neurological and
      general symptoms, but it is unknown whether these abnormalities are shared by
      "traditional" MVP. In conclusion, MVP is probably a multi-factorial process, and
      many aspects still need to be clarified. As surgery can only correct the damaged
      valve but not the underlying mechanisms, a more complete knowledge of the
      involved molecular pathways is necessary, as it may allow the discovery of
      targeted therapeutic strategies aimed at modifying or slackening MVP natural
      course in the early phases.

PMID- 21168226
TI  - Emerging role for drug transporters at the blood-testis barrier.
AB  - Drug transporters are integral membrane proteins that transport a broad range of
      substrates into and out of cells, usually against a concentration gradient.
      Studies have shown that efflux pumps such as P-glycoprotein (P-gp) and breast
      cancer resistance protein (BCRP) localize at the blood-testis barrier (BTB),
      where they protect the testis from drugs and xenobiotics that are detrimental to
      spermatogenesis. At the same time, efflux pumps might also preclude entry of non
      hormonal contraceptives to the testis. In more recent studies, P-gp function was
      correlated with BTB integrity. In this review, we discuss findings that have made
      a significant impact on our understanding of efflux pumps in the testis.
      Modulation of efflux pump function via specific inhibitors could help to deliver
      contraceptives to the testis in the future.

PMID- 21168229
TI  - Sucrose monolaurate improves the efficacy of sodium hypochlorite against
      Escherichia coli O157:H7 on spinach.
AB  - It is well-recognized that chlorine has limited efficacy when applied to
      inactivate pathogens on fresh produce. One of the many factors limiting efficacy
      is the high interfacial tension of chlorine-based sanitizers that limits the
      access of chlorine to the microorganisms. In this work, we investigated the
      efficacy of sodium hypochlorite (200 ppm, pH 6.0) at 4 and 20  degrees C against
      Escherichia coli O157:H7 inoculated on baby spinach leaves as affected by the
      surfactant sucrose monolaurate (SML) at below (100 ppm), above (250 ppm), and
      well above (10,000 ppm) the critical micelle concentration (CMC) of ~200 ppm at
      20  degrees C. The surfactant-containing chlorine treatments were compared to
      those with buffer only, surfactant only, and chlorine only. Significantly
      improved inactivation, as evidenced by survival of E. coli O157:H7 was achieved
      when 250 or 10,000 ppm SML was added with chlorine. This is attributed to the
      reduction of interfacial tension between the sanitizing solutions and spinach
      surface. Treatments at 20  degrees C resulted in greater mean inactivation than
      those at 4  degrees C but the difference was not significant. Comparisons of SML
      concentrations in treatment solutions before and after sanitization showed that
      SML decreased more at a lower temperature and when chlorine was present,
      resulting from adsorption of SML onto spinach matrix. Our work illustrates the
      importance of using surfactants at concentrations above the CMC to enhance the
      efficacy of chlorine sanitization.

PMID- 21168230
TI  - Citrus flavonoid represses Salmonella pathogenicity island 1 and motility in S.
      Typhimurium LT2.
AB  - Salmonellosis is one of the leading health problems worldwide. With the rise of
      drug resistance strains, it has become imperative to identify alternative
      strategies to counter bacterial infection. Natural products were used
      historically to identify novel compounds with various bioactivities. Citrus
      species is a rich source of flavonoids. Naringenin, a flavonone, is present
      predominantly in grapefruit. Previously we have demonstrated that naringenin is
      potent inhibitor of cell-cell signaling. The current study was undertaken to
      understand the effect of naringenin on Salmonella Typhimurium LT2. The cDNA
      microarrays were employed to study the response of S. Typhimurium to naringenin
      treatment. Naringenin specifically repressed 24 genes in the Salmonella
      pathogenicity island 1 and down-regulated 17 genes involved in flagellar and
      motility. Furthermore, phenotypic assays support the result of microarray
      analysis. In addition, naringenin seems to repress SPI-1 in pstS/hilD-dependent
      manner. Altogether the data suggest that naringenin attenuated S. Typhimurium
      virulence and cell motility. This is the first molecular evidence to demonstrate
      effect of naringenin on bacterial virulence and cell motility.

PMID- 21168231
TI  - Weight loss in obese patients with type 2 diabetes: effects of telemonitoring
      plus a diet combination - the Active Body Control (ABC) Program.
AB  - AIMS: We evaluate the efficacy of the "Active Body Control (ABC) Program" for
      weight reduction in patients with type 2 diabetes. METHODS: The ABC program
      combines telemonitoring of the physical activity with a low-calorie diet also
      preferring carbohydrates with low glycemic indexes. In this 6-month, randomized,
      clinical trial 35 patients (aged 57 +/- 9 years; BMI=35.3 +/- 5.7 kg/m(2)) were
      treated according to the ABC program and 35 control patients (aged 58 +/- 7
      years; BMI=34.8 +/- 5.9 kg/m(2)) received standard therapy. RESULTS: After 6
      months the mean weight loss in the intervention group was 11.8 kg +/- 8.0 kg.
      Glucose and HbA1c were lowered by respectively 1.0 mmol/l and 0.8 percentage
      points (p=0.000, respectively). The proportion of patients with HbA1c>7% fell
      from 57% to 26%. Antidiabetic drugs were discontinued in 13 patients (39%) and
      reduced in 14 (42%). The reduction of costs on medication per patient was ? 83 in
      6 months. In the control group, there were no relevant changes in body weight,
      laboratory values or drug treatment. CONCLUSIONS: The ABC program effectively
      lowers body weight, Hb1Ac and antidiabetic drug use in patients with type 2
      diabetes.

PMID- 21168232
TI  - Feasibility of group lifestyle intervention for diabetes prevention in Arab
      Americans.
AB  - AIMS: To assess the feasibility and acceptability of a community-based,
      culturally-specific, Diabetes Prevention Program (DPP)-adapted, group lifestyle
      intervention in Arab-Americans. METHODS: Overweight (BMI >= 27 kg/m(2)) Arab
      Americans aged >= 30 years and without a history of diabetes were recruited to
      participate in a 24-week group lifestyle intervention. The DPP core-curriculum
      was culturally rewritten, translated into Arabic, and delivered in weekly
      sessions over a 12-week period. Follow-up was performed at week-24. The primary
      goals were to achieve >= 7% weight loss and >= 150 min/week of physical activity.
      An intent-to-treat analysis was performed. RESULTS: Of the 71 participants (mean
      age +/- SD 47 +/- 10 years, 38% males), 44% achieved >= 7% weight loss, 59%
      achieved >= 5% reduction in weight, and 78% reached the physical activity goal of
      >= 150-min/week. The mean +/- SD weight loss was 5.2 +/- 4.4 kg at week-24
      (p<0.0001), Marked reduction in body measurements, daily energy and fat intake
      were noted. Retention was high with 86% completing the intervention. CONCLUSIONS:
      This trial demonstrates that a culturally-specific, DPP-adapted, group lifestyle
      intervention implemented in a community setting is feasible and effective in Arab
      Americans.

PMID- 21168233
TI  - HNF1 alpha gene coding regions mutations screening, in a Caucasian population
      clinically characterized as MODY from Argentina.
AB  - INTRODUCTION: There are at least six subtypes of Maturity Onset Diabetes of the
      Young (MODY) with distinctive genetic causes. MODY 3 is caused by mutations in
      HNF1A gene, an insulin transcription factor, so mutations in this gene are
      associated with impaired insulin secretion. MODY 3 prevalence differs according
      to the population analyzed, but it is one of the most frequent subtypes.
      Therefore, our aims in this work were to find mutations present in the HNF1A gene
      and provide information on their prevalence. MATERIAL AND METHODS: Mutations
      screening was done in a group of 80 unrelated patients (average age 17.1 years)
      selected by clinical characterization of MODY, by SSCP electrophoresis followed
      by sequenciation. RESULTS: We found eight mutations, of which six were novel and
      four sequence variants, which were all novel. Therefore the prevalence of MODY 3
      in this group was 10%. Compared clinical data between the non-MODY 3 patients and
      the MODY 3 diagnosed patients did not show any significant difference.
      DISCUSSION: Eight patients were diagnosed as MODY 3 and new data about the
      prevalence of that subtype is provided. Our results contribute to reveal novel
      mutations, providing new data about the prevalence of that subtype.

PMID- 21168234
TI  - Clustering technique-based least square support vector machine for EEG signal
      classification.
AB  - This paper presents a new approach called clustering technique-based least square
      support vector machine (CT-LS-SVM) for the classification of EEG signals.
      Decision making is performed in two stages. In the first stage, clustering
      technique (CT) has been used to extract representative features of EEG data. In
      the second stage, least square support vector machine (LS-SVM) is applied to the
      extracted features to classify two-class EEG signals. To demonstrate the
      effectiveness of the proposed method, several experiments have been conducted on
      three publicly available benchmark databases, one for epileptic EEG data, one for
      mental imagery tasks EEG data and another one for motor imagery EEG data. Our
      proposed approach achieves an average sensitivity, specificity and classification
      accuracy of 94.92%, 93.44% and 94.18%, respectively, for the epileptic EEG data;
      83.98%, 84.37% and 84.17% respectively, for the motor imagery EEG data; and
      64.61%, 58.77% and 61.69%, respectively, for the mental imagery tasks EEG data.
      The performance of the CT-LS-SVM algorithm is compared in terms of classification
      accuracy and execution (running) time with our previous study where simple random
      sampling with a least square support vector machine (SRS-LS-SVM) was employed for
      EEG signal classification. We also compare the proposed method with other
      existing methods in the literature for the three databases. The experimental
      results show that the proposed algorithm can produce a better classification rate
      than the previous reported methods and takes much less execution time compared to
      the SRS-LS-SVM technique. The research findings in this paper indicate that the
      proposed approach is very efficient for classification of two-class EEG signals.

PMID- 21168235
TI  - Creating "denial" typologies is ontologically questionable.

PMID- 21168236
TI  - Assessment of lung-cancer mortality reduction from CT Screening.
AB  - BACKGROUND: CT screening has been shown to increase lung cancer curability and we
      now assess the corresponding reduction in lung cancer mortality. METHODS: Lung
      cancer mortality in a cohort of 7995 smokers who underwent CT screening for lung
      cancer in New York State (NYS) was compared with two unscreened cohorts (CPS-II
      and CARET). The standardized mortality ratio (SMR) of observed to expected lung
      cancer deaths for NYS was jointly adjusted for age, sex, and smoking history. As
      more current NYS smokers might have quit as a result of the screening, thus
      reducing deaths from lung cancer, another analysis was restricted to those
      participants smoking at entry and still smoking 6 years later. RESULTS: The SMR
      was 64/99.8=0.64 (P = 0.84 * 10-4) and 28/77.6=0.36 (P = 0.83 * 10-10), showing a
      significant reduction in deaths from lung cancer of 36% and 64% for CPS-II and
      CARET, respectively. Considering participants who were smoking at entry and still
      smoking 6 years later, the SMR using CPS-II rates was 29/49.1 = 0.59 (P = 0.001)
      and using CARET rates it was 21/57.4 = 0.37 (P = 0.31 * 10-7). CONCLUSIONS: CT
      screening significantly reduces lung-cancer mortality.

PMID- 21168237
TI  - Factors associated with recurrence in patients with curatively resected stage I
      II lung cancer.
AB  - BACKGROUND: Patients with stage I-II non-small cell lung cancer (NSCLC) show
      variability in recurrence after curative resection. Several factors have been
      proposed as prognostic of recurrence in previous studies. However, because of the
      heterogeneity of the populations studied, these reports did not yield consistent
      results. The aim of our study was to identify risk factors for recurrence in
      patients with curatively resected stage I-II NSCLC. METHODS: We reviewed the
      medical records of pathological stage I-II NSCLC patients after curative surgery
      performed in a tertiary referral center (Seoul National University Hospital) from
      January 2002 to December 2004. Demographic factors, radiological,
      histopathological, and laboratory findings, and surgery-related factors were
      analyzed. Patients with invasive cancer other than lung cancer that was present 5
      years prior to surgery were excluded. The Cox proportional hazard regression
      model was used for multivariate analyses. RESULTS: Three hundred and ten patients
      were included. Among them, local recurrence occurred in 27 patients (8.7%),
      whereas distant recurrence occurred in 79 patients (25.5%). Adenocarcinoma
      histology (OR, 2.74; 95% CI, 1.14-6.58; P=0.024), carcinoembryonic antigen (CEA)
      level>2.3 ng/mL (OR, 2.26; 95% CI, 1.02-5.00; P=0.045), and standard uptake
      values (SUV) of tumor in positron emission tomography (PET)>4.5 (OR, 5.45; 95%
      CI, 1.82-16.31; P=0.002) were independent predictors of recurrence in addition to
      TNM stage. We also constructed a recurrence prediction model based on these
      findings, which yielded better diagnostic performance than the TNM staging
      system. CONCLUSION: Adenocarcinoma histology, CEA level, and SUV of PET could be
      considered as prognostic factors for recurrence in patients with curatively
      resected stage I-II NSCLC.

PMID- 21168238
TI  - The outcome differences of CT screening for lung cancer pre and post following an
      algorithm in Zhuhai, China.
AB  - PURPOSE: To evaluate the change in outcomes from CT screening for lung cancer
      before and after collaboration with the International Early Lung Cancer Action
      Program (I-ELCAP) as well as changing from a single-row detector to a multi-row
      detector CT scanner (MDCT). METHODS AND MATERIALS: All participants in the
      screening program were 40 years of age and older. From 1994 to 2002, a single
      slice spiral CT was used, the screening protocol was established empirically at
      our institution. From 2003 to 2009 a 16 slice MDCT was used and our institute
      became the first I-ELCAP site in China. Collaboration included use of the I-ELCAP
      protocol, image reading training, teaching files training and attendance at
      international conferences. The clinical and CT characteristics of participants
      and diagnosed lung cancers pre and post-collaboration were summarized. The
      outcomes before and after collaboration were compared, including nodule positive
      rate, lung cancer frequency, stage distribution, pathology, intervals between
      last routine screening and surgery, the rate of surgery for benign disease and
      survival rate. RESULTS: 3348 participants were enrolled during 1994-2002 and 3582
      participants during 2003-2009. Their age, gender, smoking and family cancer
      histories were comparable. The screening detection rate of lung cancer was 1.1%
      (36/3348) vs. 1.0% (34/3582) (P=0.6), mean size was 18.6 mm vs. 15.6 mm (P=0.04),
      stage I lung cancer was 67% vs. 91% (P=0.38), median intervals between last
      routine screening and surgery was 213 days vs. 96 days (P<0.001), 5-year survival
      rate due to lung cancer was 75% vs. 95% (P=0.032) in pre- and post collaboration
      group respectively. The nodule positive rate was 6.2% (208/3348) vs. 9.8%
      (351/3582) (P<0.001), the rate of surgery for benign disease was 18% (8/44) vs.
      8% (3/37) (P=0.4) in pre- and post collaboration group respectively. CONCLUSION:
      Smaller lung cancer were detected, interval between last routine screening and
      surgery was shorter, surgery for benign disease decreased, and survival rate
      increased in CT screening for lung cancer in Zhuhai after the collaboration with
      I-ELCAP and with MDCT. Technology improvements along with a well defined protocol
      improved outcomes of CT screening for lung cancer in Zhuhai, China.

PMID- 21168239
TI  - Clinical and molecular evidences of epithelial to mesenchymal transition in
      acquired resistance to EGFR-TKIs.
AB  - BACKGROUND: Epithelial-to-mesenchymal transition (EMT), which was related with an
      acquired resistance to gefitinib, was found in the A549 lung cancer cell line.
      However, the clinical feasibility of this finding is still questionable. Here, we
      investigated whether EMT could be detected in a more clinically suitable
      situation using patient's tumor and cells with deletion mutation on exon 19 of
      EGFR gene. METHODS: HCC827 cell line was used to establish the subline resistant
      to EGFR-TKIs. The induction of EMT was analyzed by immunostainings and Western
      blots in resistant cells and biopsied tissue from a patient with acquired
      resistance to erlotinib. Migration and invasion assay was performed to
      characterize the resistant cells. EMT-related genes expression was evaluated by
      cDNA microarray. Phospho-receptor tyrosine kinase array analysis was carried out
      to find bypass activating signals such as MET. RESULTS: We found that EMT
      developed in a lung cancer patient who had an acquired resistance to erlotinib
      while there were no known resistant mechanisms such as T790M and MET
      amplification. CL-387,785-resistant cells (HCC827/CLR) were obtained by long-term
      exposure to increasing concentrations of CL-387,785 (an irreversible EGFR-TKI).
      The morphological and molecular maker changes compatible with EMT were also found
      in HCC827/CLR cells. However, there were also no secondary T790M mutation and MET
      amplification. Furthermore, the activity of most of tested RTKs including
      receptor HER family was decreased suggesting that there was no bypass activating
      signal leading to resistance. These cells showed an enhanced capability for
      migration (~1.6-fold) and invasion (~2.8-fold). CONCLUSION: EMT should be
      considered as one of possible mechanisms for the acquired resistance to EGFR-TKIs
      in lung cancer cells.

PMID- 21168240
TI  - Collagen induced arthritis (CIA) in mice features regulatory transcriptional
      network connecting major histocompatibility complex (MHC H2) with autoantigen
      genes in the thymus.
AB  - Considering that imbalance of central tolerance in the thymus contributes to
      aggressive autoimmunity, we compared the expression of peripheral tissue
      autoantigens (PTA) genes, which are involved in self-representation in the thymic
      stroma, of two mouse strains; DBA-1/J (MHC-H2(q)) susceptible and DBA-2/J (MHC
      H2(d)) resistant to collagen induced arthritis (CIA). We evaluate whether these
      strains differ in their thymic gene expression, allowing identification of genes
      that might play a role in susceptibility/resistance to CIA. Microarray profiling
      showed that 1093 PTA genes were differentially modulated between collagen
      immunized DBA-1/J and DBA-2/J mice. These genes were assigned to 17 different
      tissues/organs, including joints/bone, characterizing the promiscuous gene
      expression (PGE), which is implicated in self-representation. Hierarchical
      clustering of microarray data and quantitative RT-PCR analysis showed that Aire
      (autoimmune regulator), an important regulator of the PGE process, Aire-dependent
      (insulin), Aire-independent (Col2A1 and Gad67), and other 22 joint/bone
      autoantigen genes were down-regulated in DBA-1/J compared with DBA-2/J in the
      thymus. Considering the importance of MHC-H2 in peptide-self presentation and
      autoimmunity susceptibility, we reconstructed transcriptional networks of both
      strains based on actual microarray data. The networks clearly demonstrated
      different MHC-H2 transcriptional interactions with PTAs genes. DBA-1/J strain
      featured MHC-H2 as a node influencing downstream genes. Differently, in DBA-2/J
      strain network MHC-H2 was exclusively self-regulated and does not control other
      genes. These findings provide evidence that CIA susceptibility in mice may be a
      reflex of a cascade-like transcriptional control connecting different genes to
      MHC-H2 in the thymus.

PMID- 21168241
TI  - Chlorophenoxyacetic acid and chloropyridylphenylurea accelerate translocation of
      photoassimilates to parthenocarpic and seeded fruits of muskmelon (Cucumis melo).
AB  - We compared the effect of p-chlorophenoxyacetic acid (p-CPA) and 1-(2-chloro-4
      pyridyl)-3-phenylurea (CPPU) on parthenocarpic and seeded muskmelon (Cucumis
      melo) fruits in regards to fruit development and the transport of
      photoassimilates from leaves exposed to 14CO2 to the developing fruits. Ten days
      after anthesis (DAA), the fresh weight, total 14C-radioactivity and contents of
      14C-sucrose and 14C-fructose were higher in the CPPU-induced parthenocarpic
      fruits than in seeded fruits. However, at 35 DAA, fresh weight and sucrose
      content in mesocarp, placenta and empty seeds of the parthenocarpic fruits were
      lower than in seeded fruits. Also, total 14C-radioactivity and 14C-sugar content
      of the parthenocarpic fruits were lower as well as the translocation rate of 14C
      photoassimilates into these fruits. Application of p-CPA to the parthenocarpic
      fruits at 10 and 25 DAA increased fresh weight and sugar content. Moreover, these
      treatments elevated the total 14C-radioactivity, 14C-sucrose content and the
      translocation rate of 14C-photoassimilates. The 14C-radioactivity along the
      translocation pathway from leaf to petiole, stem, lateral shoot and peduncle
      showed a declining pattern but dramatically increased again in the fruits. These
      results suggest that the fruit's sink strength was regulated by the seed and
      enhanced by the application of p-CPA.

PMID- 21168242
TI  - Recurrent sebaceous gland carcinoma of eyelid previously diagnosed as basal cell
      carcinoma: case report.
AB  - Sebaceous gland carcinoma (SGC) of the eyelid is a highly malignant neoplasm that
      arises from the meibomian glands, glands of Zeis, and sebaceous glands of the
      skin. The characteristics of this disease are high recurrence rate, significant
      metastatic potential, and notable mortality rate, which are quite different from
      basal cell carcinoma (BCC). We report the case of a 37-year-old woman with the
      history of left lower eyelid BCC (diagnosed 9 years ago), who had left parotid
      lymph nodes metastases and local recurrence twice. The chief complaint during
      visit was a left upper eyelid swelling mass noted for 3 months. She received
      salvage ablation surgery later. The final pathologic report is SGC. The diagnosis
      corresponds to the clinical presentation of this patient at last. The delay
      between initial examination and final diagnosis in this patient is about 9 years,
      but operation and concurrent chemotherapy and radiotherapy were performed after
      left parotid lymph nodes metastasis was noted. Although there was still local
      recurrence after concurrent chemotherapy and radiotherapy, the patient is still
      alive without distant metastasis. In this article, we would discuss the
      differences of the pathologic characters, treatment, and prognosis between SGC
      and BCC.

PMID- 21168243
TI  - [Utility of infliximab therapy in severe enterorrhagia associated with Crohn's
      disease. Report of three cases].
AB  - Severe lower gastrointestinal (GI) bleeding is an infrequent complication in
      Crohn's disease. We report the cases of three patients with Crohn's disease,
      localized in distinct areas, who developed severe enterorrhagia requiring
      multiple transfusions. All three patients responded favorably to infliximab
      administration, which resolved the life-threatening hemorrhages and avoided
      emergency surgical resection, which had seemed inevitable. Based on this clinical
      experience and a review of the literature comparing infliximab with other
      pharmacological options, we believe that this drug should be the treatment of
      choice in patients with Crohn's disease who develop severe lower gastrointestinal
      bleeding. This strategy can, in some cases, avoid surgery if the bleeding stops
      due to rapid healing of the deep mucosal lesions causing the hemorrhagic episode.

PMID- 21168245
TI  - Rethinking the admission criteria to nursing school.
AB  - The main objective of this study was to identify the best predictors for student
      achievements (Undergraduate Grade Point Average (UGPA)) in their first year in an
      undergraduate nursing programme. Data were acquired from the Tracking Project
      database which is held by the Faculty of Medical and Health Sciences at the
      University of Auckland. The data (n=134) included information on student
      demographics, final year secondary school achievements (National Certificate of
      Educational Achievement Grade Point Average (NCEAGPA) & NCEA Credits), university
      admission ranking scores, and achievements in first year in the undergraduate
      nursing programme (UGPA). Linear regression models were used to identify the best
      predictors for first year students' UGPA in the nursing programme. The regression
      models suggest that the best predictor for the first year GPA is the NCEAGPA
      (beta=.488; R(2)(for the entire model)=.53), followed by the admission ranking
      scores (beta=.308; R(2)=.40). Based on these findings, it is suggested that a
      Dual Admission Model (DAM) be utilised whereby students could be admitted either
      by the current university admission criteria or by an alternative model, which is
      purely based on the predictability of achievement within the nursing programme.
      Application of the DAM to other institutions/countries was discussed.

PMID- 21168244
TI  - [Nodular regenerative hyperplasia: azathioprine-induced hepatotoxicity in a
      patient with Crohn's disease].
AB  - We report the case of a 53-year-old man with Crohn's disease who developed
      azathioprine-induced nodular regenerative hyperplasia of the liver. The diagnosis
      was suspected when abnormalities in liver function tests were observed and
      transabdominal ultrasonography and upper gastrointestinal endoscopy showed signs
      of portal hypertension. The final diagnosis was established by liver biopsy,
      showing the characteristic alterations in liver architecture. Outcome was
      favorable after treatment discontinuation, with complete normalization of liver
      function tests within a year. The present article describes the incidence and the
      main clinical characteristics of this adverse effect to thiopurines.

PMID- 21168246
TI  - Salvage outcomes of free tissue transfer in Liverpool: trends over 18 years (1992
      2009).
AB  - Reconstruction of surgical defects in the head and neck using microvascular free
      tissue transfer is reliable with success rates in excess of 95%. Our previous
      audit (1992-1998) showed that 16% of patients required an early return to
      theatre, and the overall free flap salvage rate was 73%. The medical records of
      37 patients who had required early return to theatre (within 7 days) after free
      tissue transfer were analysed to ascertain the indication for reoperation, and
      whether surgical intervention had been successful, taking into account the timing
      and cause of compromise. The results of a retrospective re-audit (1999-2004 and
      2005-2009) showed that the return to theatre rate had reduced to 4% overall
      because of a reduction in the number of cases: those that required evacuation of
      a neck haematoma, and venous compromise of fasciocutaneous or perforator free
      flaps. Salvage of flaps was most successful when done within the first 24h, and
      in cases of venous compromise. Three percent of free flaps failed without
      attempted salvage; most were late failures. Overall survival (1992-2009) for
      composite free flaps (93%) was lower than for fasciocutaneous or perforator free
      flaps (96%). Between 2005 and 2009 our overall free flap survival rate was 98%.

PMID- 21168247
TI  - Outcome evaluation of ankle osteoarthritis treatments: plantar pressure analysis
      during relatively long-distance walking.
AB  - BACKGROUND: This study aimed to use plantar pressure analysis in relatively long
      distance walking for objective outcome evaluation of ankle osteoarthritis
      treatments, i.e., ankle arthrodesis and total ankle replacement. METHODS: Forty
      seven subjects in four groups: three patient groups and controls, participated in
      the study. Each subject walked twice in 50-m trials. Plantar pressure under the
      pathological foot was measured using pressure insoles. Six parameters: initial
      contact time, terminal contact time, maximum force time, peak pressure time,
      maximum force and peak pressure were calculated and averaged over trials in ten
      regions of foot. The parameters in each region were compared between patient
      groups and controls and their effect size was estimated. Besides, the
      correlations between pressure parameters and clinical scales were calculated.
      FINDINGS: We observed based on temporal parameters that patients postpone the
      heel-off event, when high force in forefoot and high ankle moment happens. Also
      based on maximum force and peak pressure, the patients apply smoothened maximum
      forces on the affected foot. In ten regions, some parameters showed improvements
      after total ankle replacement, some showed alteration of foot function after
      ankle arthrodesis and some others showed still abnormality after both surgical
      treatments. These parameters showed also significant correlation with clinical
      scales in at least two regions of foot. INTERPRETATION: Plantar pressure
      parameters in relatively long-distance trials showed to be strong tools for
      outcome evaluation of ankle osteoarthritis treatments.

PMID- 21168248
TI  - Effect of the Arizona tobacco control program on cigarette consumption and
      healthcare expenditures.
AB  - This research investigates the relationship between per capita tobacco control
      expenditures, cigarette consumption, and healthcare expenditures in the state of
      Arizona. Arizona's tobacco control program, which was established in 1994,
      concentrates on youth uptake of smoking and avoids public policy and commentary
      on the tobacco industry. We use a cointegrating time series analysis using
      aggregate data on healthcare and tobacco control expenditures, cigarette
      consumption and prices and other data. We find there is a strong association
      between per capita healthcare expenditure and per capita cigarette consumption.
      In the long run, a marginal increase in annual cigarette consumption of one pack
      per capita increases per capita healthcare expenditure by $19.5 (SE $5.45) in
      Arizona. A cumulative increase of $1.00 in the difference between control state
      and Arizona per capita tobacco control expenditures increases the difference in
      cigarette consumption by 0.190 (SE 0.0780) packs per capita. Between 1996 and
      2004, Arizona's tobacco control program was associated with a cumulative
      reduction in cigarette consumption of 200 million packs (95% CI 39.0 million
      packs, 364 million packs) worth $500 million (95% CI: $99 million, $896 million)
      in pre-tax cigarette sales to the tobacco industry. The cumulative healthcare
      savings was $2.33 billion (95% CI $0.37 billion, $5.00 billion) and the
      cumulative reduction in cigarette. Arizona's tobacco control expenditures are
      associated with reduced cigarette consumption and healthcare expenditures,
      amounting to about 10 times the cost of the program through 2004. This return on
      investment, while large, was less than the more aggressive California program,
      which did not limit its focus to youth and included tobacco industry
      denomalization messages.

PMID- 21168249
TI  - Food security and humanitarian assistance among displaced Iraqi populations in
      Jordan and Syria.
AB  - The Iraq conflict resulted in the largest displacement in the Middle East in
      recent history, and provision of health services to the displaced population
      presents a critical challenge. With an increase in the number of people affected
      by complex emergencies and the number of people displaced in urban settings, the
      international community must adapt intervention strategies to meet the specific
      demands and contexts of this population. The study aimed to provide information
      on food security and livelihoods for Iraqi refugees in Syria and Jordan to inform
      humanitarian assistance planning. National cross-sectional cluster sample surveys
      of displaced Iraqi populations displaced were conducted in Jordan (October 2008)
      and Syria (March 2009). Clusters of ten households were randomly selected using
      probability-based sampling; a total of 1200 and 813 Iraqi households in Jordan
      and Syria, respectively, were interviewed about food security and receipt of
      humanitarian assistance. In Syria, 60% of households reported the household food
      situation had declined since the arrival period as compared to 46% in Jordan.
      Food aid receipt was reported by 18.0% of households in Jordan and 90.3% of
      households in Syria. In Jordan, 10.2% of households received cash assistance and
      in Syria 25.3% of households received cash assistance. In Jordan, cash assistance
      was associated with low socioeconomic status, large household size, and UNHCR
      registration. In Syria, female headed households, Damascus residents, families
      with children, and those registered with UNHCR were more likely to receive cash
      assistance. Food insecurity remains a concern among displaced Iraqi households in
      both Jordan and Syria. Improved targeting of both food and cash assistance and
      the expansion of cash-based programs could lead to a more effective use of funds
      and facilitate the implementation of assistance programs that are sustainable in
      the context of declining funding availability.

PMID- 21168250
TI  - Translational science and the hidden research system in universities and academic
      hospitals: a case study.
AB  - Innovation systems (IS) and science policy scholarship predominantly focus on
      linkages between universities and industry, and the commercial translation of
      academic discoveries. Overlooked in such analyses are important connections
      between universities and academic hospitals, and the non-commercial aspects of
      translational science. The two types of institutions tend to be collapsed into a
      single entity-'the university'-and relational flows are lost. Yet the
      distinctions and flows between the two are crucial elements of translational
      science and the biomedical innovation system. This paper explores what has been
      called the 'hidden research system' that connects hospitals, universities, and
      their resources, with the clinical and scientific actors who make the linkages
      possible. Then, using a novel conceptual model of translational science, we
      examine the individual interactions and dynamics involved in a particular example
      of the biomedical innovation system at work: the diagnosis of IRAK-4 deficiency,
      a rare immunological disorder, and the translational flows that result. Contra to
      conventional IS analyses, we are able to point to the strong role of public
      sector institutions, and the weak role of the private-sector, in the
      translational processes described here. Our research was conducted within a
      Canadian network of scientists and clinician-scientists studying the
      pathogenomics of immunological disorders and innate immunity.

PMID- 21168251
TI  - Giant submental dermoid cysts with near total obstruction of the oral cavity:
      report of 2 cases.
AB  - Dermoid cysts in the head and neck are a relatively uncommon entity with only
      6.9% occurring in this site. They most commonly occur in the lateral third of the
      eyebrow with 26% found in the floor of the mouth.(1) They are believed to arise
      from failure of the overlying surface ectoderm to separate from underlying
      structures. Typically, dermoid cysts present as slow-growing nontender midline
      floor of the mouth or submental swellings that can develop to significant
      dimensions before producing symptoms.(2) We report 2 such cases where large
      dermoid cysts produced progressive dysphagia and breathing difficulty, resulting
      in acute presentation to our service.

PMID- 21168253
TI  - Infantile sinonasal myxoma: a unique variant of maxillofacial myxoma.

PMID- 21168252
TI  - Prevalence of visible third molars with caries experience or periodontal
      pathology in middle-aged and older Americans.
AB  - PURPOSE: To assess the prevalence of periodontal pathology and caries experience
      in visible third molars, as well as the relationship of these findings to
      periodontal pathology and caries experience in teeth more anterior in the mouth.
      PATIENTS AND METHODS: Data were from 6,793 Dental Atherosclerosis Risk in
      Communities participants who underwent a clinical examination for periodontal
      disease and coronal caries experience and who retained at least 1 visible third
      molar. Outcome variables were the detection of periodontal pathology or coronal
      caries experience on visible third molars and on teeth more anterior in the mouth
      (non-third molars). Periodontal probing depths at least 4 mm (PD4+) and clinical
      attachment levels at least 3 mm (CAL3+) were indicator variables for periodontal
      pathology. At least 1 carious/decayed coronal surface or filled coronal surface
      was an indicator variable for caries experience. Outcomes for third molar and non
      third molar teeth were compared by descriptive statistics and chi(2) tests with
      statistical significance set at P < .05. RESULTS: A third of the 6,793 Dental
      Atherosclerosis Risk in Communities subjects, who averaged 62 years of age, had
      at least 1 visible third molar. Subjects were more likely to have at least 1
      third molar CAL3+ as compared with at least 1 third molar PD4+: 78% versus 61%.
      PD4+ and CAL3+ were significantly more prevalent among non-third molars as
      compared with third molars (P < .01). Most subjects, 73%, had restorations on
      visible third molars and non-third molars, and over two-thirds of subjects had a
      visible third molar with caries experience and periodontal pathology. Fewer than
      2% of subjects had third molars free of caries experience or periodontal
      pathology. CONCLUSIONS: Most subjects had clinical evidence of caries experience
      or periodontal pathology on visible third molars; few subjects had visible third
      molars that were disease free. Subjects with periodontal pathology or caries
      experience on third molars were significantly more likely to have these findings
      detected on teeth more anterior in the mouth.

PMID- 21168254
TI  - Bag-mask ventilation may be life-saving with foreign body tracheal obstruction.

PMID- 21168255
TI  - Airway scope-assisted intubation during cardiopulmonary resuscitation without
      interruption of chest compression: the influence of chest compression rates.

PMID- 21168256
TI  - Sulfite sensitivity in a patient with allergic asthma.

PMID- 21168257
TI  - Efficacy of transient abdominal ovariopexy in patients with severe endometriosis.
AB  - OBJECTIVE: To assess adhesion formation and fertility outcome after transient
      abdominal ovariopexy performed in patients with severe endometriosis. STUDY
      DESIGN: Retrospective study including 218 patients who underwent surgery for
      severe endometriosis from 1997 to 2009. One hundred and thirty-nine (64%)
      patients were infertile. The initial ASRM stage was IV in 139 cases, III in 43
      cases and II in 36 cases. Adnexal adhesions were scored by using the Operative
      Laparoscopy Study Group (OLSG) and modified AFS scoring systems. Unilateral or
      bilateral transient abdominal ovariopexy of 336 ovaries was performed to prevent
      adhesion formation or reformation for extensive surgery. In patients who
      underwent a second operation, adnexal adhesion scores were reported. Fertility
      outcome was evaluated by a questionnaire. RESULTS: Second-look surgery was
      performed after 11.7 +/- 2.4 months in 24 patients (11%) who had undergone 38
      ovariopexies. Transient abdominal ovariopexy significantly decreased adnexal
      adhesion scores (p<0.05). Regarding fertility outcome, the median follow up was
      19.6 +/- 1.5 months. Fifty-eight patients, out of 105 infertile women who
      actively tried to conceive after surgery, conceived, 21 (36%) spontaneously and
      37 (64%) after ART. The median time interval for conception was 8.6 +/- 1 months.
      CONCLUSION: In patients with severe endometriosis, transient abdominal ovariopexy
      is an effective technique in preventing postoperative adhesion formation and in
      improving fertility outcome. CONDENSATION: In 218 patients with severe
      endometriosis, transient abdominal ovariopexy was an effective technique in
      preventing adhesion formation and improving fertility outcome.

PMID- 21168258
TI  - Branching morphogenesis: from individual molecules to a systems biology approach:
      commentary on "Sema4C-Plexin B2 signalling modulates ureteric branching in
      developing kidney" by Perala et al.

PMID- 21168259
TI  - Learning and adaptation in the management of waterfowl harvests.
AB  - A formal framework for the adaptive management of waterfowl harvests was adopted
      by the U.S. Fish and Wildlife Service in 1995. The process admits competing
      models of waterfowl population dynamics and harvest impacts, and relies on model
      averaging to compute optimal strategies for regulating harvest. Model weights,
      reflecting the relative ability of the alternative models to predict changes in
      population size, are used in the model averaging and are updated each year based
      on a comparison of model predictions and observations of population size. Since
      its inception the adaptive harvest program has focused principally on mallards
      (Anas platyrhynchos), which constitute a large portion of the U.S. waterfowl
      harvest. Four competing models, derived from a combination of two survival and
      two reproductive hypotheses, were originally assigned equal weights. In the last
      year of available information (2007), model weights favored the weakly density
      dependent reproductive hypothesis over the strongly density-dependent one, and
      the additive mortality hypothesis over the compensatory one. The change in model
      weights led to a more conservative harvesting policy than what was in effect in
      the early years of the program. Adaptive harvest management has been successful
      in many ways, but nonetheless has exposed the difficulties in defining management
      objectives, in predicting and regulating harvests, and in coping with the
      tradeoffs inherent in managing multiple waterfowl stocks exposed to a common
      harvest. The key challenge now facing managers is whether adaptive harvest
      management as an institution can be sufficiently adaptive, and whether the
      knowledge and experience gained from the process can be reflected in higher-level
      policy decisions.

PMID- 21168260
TI  - Adaptive management for a turbulent future.
AB  - The challenges that face humanity today differ from the past because as the scale
      of human influence has increased, our biggest challenges have become global in
      nature, and formerly local problems that could be addressed by shifting
      populations or switching resources, now aggregate (i.e., "scale up") limiting
      potential management options. Adaptive management is an approach to natural
      resource management that emphasizes learning through management based on the
      philosophy that knowledge is incomplete and much of what we think we know is
      actually wrong. Adaptive management has explicit structure, including careful
      elucidation of goals, identification of alternative management objectives and
      hypotheses of causation, and procedures for the collection of data followed by
      evaluation and reiteration. It is evident that adaptive management has matured,
      but it has also reached a crossroads. Practitioners and scientists have developed
      adaptive management and structured decision making techniques, and mathematicians
      have developed methods to reduce the uncertainties encountered in resource
      management, yet there continues to be misapplication of the method and
      misunderstanding of its purpose. Ironically, the confusion over the term
      "adaptive management" may stem from the flexibility inherent in the approach,
      which has resulted in multiple interpretations of "adaptive management" that fall
      along a continuum of complexity and a priori design. Adaptive management is not a
      panacea for the navigation of 'wicked problems' as it does not produce easy
      answers, and is only appropriate in a subset of natural resource management
      problems where both uncertainty and controllability are high. Nonetheless, the
      conceptual underpinnings of adaptive management are simple; there will always be
      inherent uncertainty and unpredictability in the dynamics and behavior of complex
      social-ecological systems, but management decisions must still be made, and
      whenever possible, we should incorporate learning into management.

PMID- 21168261
TI  - The consequences of backcountry surface disposal of human waste in an alpine,
      temperate forest and arid environment.
AB  - Surface disposal of human waste by the smear method, a suggested but heretofore
      unexamined technique, was tested in three environments and examined for
      reductions in fecal mass and fecal indicator bacteria. Substantial reduction in
      fecal mass was observed after six and fourteen weeks of exposure in all
      environments, but extensive reduction in fecal indicator bacteria was observed in
      only the arid and alpine environments. Although surface smears appear favorable
      to cathole techniques in terms of indicator bacteria reduction, the application
      of this method is limited by several other factors common to backcountry
      sanitation situations. It is therefore likely that surface disposal would only be
      applicable in very remote, low use, alpine and arid settings where lack of soil
      development precludes the use of catholes and carry-out techniques are otherwise
      impractical.

PMID- 21168262
TI  - A letter regarding diagnostic accuracy of ultrasound and 18-F-FDG PET or PET/CT
      for patients with suspected recurrent papillary thyroid carcinoma.

PMID- 21168264
TI  - Chronic administration of ethanol leads to an increased incidence of
      hepatocellular adenoma by promoting H-ras-mutated cells.
AB  - This study used tissue samples from male B6C3F1 mice treated with ethanol in
      drinking water (0%, 2.5%, or 5%) for 4 or 104 weeks. We tested whether chronic
      alcohol drinking promotes oxidative stress in the liver and characterized the
      mutation profile of spontaneous and ethanol-induced tumors. We show that ethanol
      does not cause detectable oxidative stress in the liver at any time point and
      acts by promoting H-ras mutated cells.

PMID- 21168265
TI  - Resveratrol enhances the anti-tumor activity of the mTOR inhibitor rapamycin in
      multiple breast cancer cell lines mainly by suppressing rapamycin-induced AKT
      signaling.
AB  - The anti-tumor activity of rapamycin is compromised by the feedback-loop-relevant
      hyperactive PI3K and ERK-MAPK pathway signaling. In breast cancer cells treated
      with rapamycin, we observed a moderate increase of AKT phosphorylation (P-AKT) in
      a rapamycin resistant cell line, MDA-MB-231, as well as a slight increase of P
      AKT in a rapamycin sensitive cell line, MCF-7. We found that resveratrol, a
      natural phytoalexin, suppressed the phosphorylation and activation of the
      PI3K/AKT pathway in all the three breast cancer cell lines that we tested. It
      also had a weak inhibitory effect on the activation of the mTOR/p70S6K pathway in
      two cell lines expressing wildtype PTEN, MCF-7 and MDA-MB-231. The combined use
      of resveratrol and rapamycin resulted in modest additive inhibitory effects on
      the growth of breast cancer cells, mainly through suppressing rapamycin-induced
      AKT activation. We, therefore, reveal a novel combination whereby resveratrol
      potentiates the growth inhibitory effect of rapamycin, with the added benefit of
      preventing eventual resistance to rapamycin, likely by suppressing AKT signaling.
      We also present data herein that PTEN is an important contributor to
      resveratrol's growth suppressive effects and its potentiation of rapamycin in
      this therapeutic scenario, as resveratrol's suppression of rapamycin-mediated
      induction of P-AKT is both PTEN-dependent and -independent. Thus, the resveratrol
      rapamycin combination may have therapeutic value in treating breast cancer and
      perhaps other processes where mTOR is activated.

PMID- 21168266
TI  - Molecular targets of celastrol derived from Thunder of God Vine: potential role
      in the treatment of inflammatory disorders and cancer.
AB  - Identification of active constituents and their molecular targets from
      traditional medicine is an enormous opportunity for modern pharmacology.
      Celastrol is one such compound that was originally identified from traditional
      Chinese medicine (Thunder of God Vine) almost three decades ago and generally
      used for the treatment of inflammatory and auto-immune diseases. Celastrol has
      attracted great interest recently, especially for its potential anti-inflammatory
      and anti-cancer activities. The anti-inflammatory effects of this triterpene have
      been demonstrated in animal models of different inflammatory diseases, including
      arthritis, Alzheimer's disease, asthma, and systemic lupus erythematosus. This
      triterpene has also been found to inhibit the proliferation of a variety of tumor
      cells and suppress tumor initiation, promotion and metastasis in various cancer
      models in vivo. Celastrol's ability to modulate the expression of pro
      inflammatory cytokines, MHC II, HO-1, iNOS, NF-kappaB, Notch-1, AKT/mTOR, CXCR4,
      TRAIL receptors DR4 and DR5, CHOP, JNK, VEGF, adhesion molecules, proteasome
      activity, topoisomerase II, potassium channels, and heat shock response has been
      reported. This review describes the various molecular targets of celastrol,
      cellular responses to celastrol, and animal studies with celastrol in cancer and
      other inflammatory disorders.

PMID- 21168267
TI  - Co-treatment of single, binary and ternary mixture gas of ethanethiol, dimethyl
      disulfide and thioanisole in a biotrickling filter seeded with Lysinibacillus
      sphaericus RG-1.
AB  - The work reports the aerobic co-treatment characteristics of single, binary and
      ternary mixture gas of ethanethiol, dimethyl disulfide (DMDS) and thioanisole in
      a biotrickling filter seeded with Lysinibacillus sphaericus RG-1. 100% removal
      efficiency (RE) was achieved for sole ethanethiol, DMDS and thioanisole at inlet
      concentration below 1.05, 0.81 and 0.33 mg/L, respectively, at empty bed resident
      time 110 s. In addition, 100% RE was also obtained with binary ethanethiol and
      DMDS (1:1) and ternary ethanethiol, DMDS and thioanisole (3:2:1). Michaelis
      Menten equation was modified to incorporate the plug flow behavior of the
      bioreactor. The maximum removal rate (V(max)) was calculated as 56.18, 57.14 and
      22.78 g/m(3)/h for sole ethanethiol, DMDS and thioanisole, respectively, while
      the V(max) was 41.84 and 14.56 g/m(3)/h for DMDS and thioanisole in binary and
      ternary systems, respectively. Overall, these suggest that not only sole but also
      binary and ternary mixture can be efficiently removed in this system.

PMID- 21168268
TI  - Adsorption of chromium(VI) and Rhodamine B by surface modified tannery waste:
      kinetic, mechanistic and thermodynamic studies.
AB  - In this study, various activation methods have been employed to examine the
      potential reuse of tannery residual biomass (TRB) obtained from vegetable tanning
      process for the removal of Cr(VI) and Rhodamine B (RB) from aqueous solution. The
      maximum BET surface area (10.42 m(2)/g), honey comb pore distribution and uptake
      of both Cr(VI) and RB were achieved when only 3-fold volume of HCl was used to
      activate the biomass. The pH and temperature experiment showed that they have
      considerable impact on the adsorption capacity of the used adsorbent. The
      presence of other ions (Na(+), Ca(2+) and NH(4)(+)) significantly reduces the
      metal uptake but marginal enhancement in the dye removal was observed when Na(+)
      and NH(4)(+) ions were present in the solution. The equilibrium data fitted
      satisfactorily with the Langmuir model and monolayer sorption capacity obtained
      as 177-217 and 213-250 mg/g for Cr(VI) and RB at 30-50 degrees C, respectively.
      The sorption kinetics was found to follow the pseudo-second-order kinetic model.
      The increase in adsorption capacity for both metal and dye with increase in
      temperature indicates that the uptake was endothermic in nature. The results
      indicate that the HCl modified TRB (A-TRB) could be employed as a low cost
      adsorbent for the removal of both Cr(VI) and RB from the aqueous solution
      including industrial wastewater.

PMID- 21168269
TI  - Preparation and characterization of porous granular ceramic containing dispersed
      aluminum and iron oxides as adsorbents for fluoride removal from aqueous
      solution.
AB  - Porous granular ceramic adsorbents containing dispersed aluminum and iron oxides
      were synthesized by impregnating with salt solutions followed by precipitation at
      600 degrees C. In the present work detailed studies were carried out to
      investigate the effect of contact time, adsorbent dose, initial solution pH and
      co-existing anions. Characterization studies on the adsorbent by SEM, XRD, EDS,
      and BET analysis were carried out to clarify the adsorption mechanism. The
      adsorbents were sphere in shape, 2-3mm in particle size, highly porous and showed
      specific surface area of 50.69 sq m/g. The fluoride adsorption capacity of
      prepared adsorbent was 1.79 mg/g, and the maximum fluoride removal was obtained
      at pH 6. Both the Langmuir and Freundlich isotherm models were found to represent
      the measured adsorption data well. The experimental data were well explained with
      pseudo-second-order kinetic model. Results from this study demonstrated potential
      utility of Al/Fe dispersed in porous granular ceramics that could be developed
      into a viable technology for fluoride removal from aqueous solution.

PMID- 21168270
TI  - Is chronic migraine a never-ending migraine attack?

PMID- 21168271
TI  - Human odontoblasts express functional thermo-sensitive TRP channels: implications
      for dentin sensitivity.
AB  - Odontoblasts form the outermost cellular layer of the dental pulp where they have
      been proposed to act as sensory receptor cells. Despite this suggestion, evidence
      supporting their direct role in mediating thermo-sensation and nociception is
      lacking. Transient receptor potential (TRP) ion channels directly mediate
      nociceptive functions, but their functional expression in human odontoblasts has
      yet to be elucidated. In the present study, we have examined the molecular and
      functional expression of thermo-sensitive TRP channels in cultured odontoblast
      like cells and in native human odontoblasts obtained from healthy wisdom teeth.
      PCR and western blotting confirmed gene and protein expression of TRPV1, TRPA1
      and TRPM8 channels. Immunohistochemistry revealed that these channels were
      localised to odontoblast-like cells as determined by double staining with dentin
      sialoprotein (DSP) antibody. In functional assays, agonists of TRPV1, TRPA1 and
      TRPM8 channels elicited [Ca2+]i transients that could be blocked by relevant
      antagonists. Application of hot and cold stimuli to the cells also evoked rises
      in [Ca2+]i which could be blocked by TRP-channel antagonists. Using a gene
      silencing approached we further confirmed a role for TRPA1 in mediating noxious
      cold responses in odontoblasts. We conclude that human odontoblasts express
      functional TRP channels that may play a crucial role in mediating thermal
      sensation in teeth. Cultured and native human odontoblasts express functional TRP
      channels that may play a crucial role in mediating thermal sensation in teeth.

PMID- 21168272
TI  - Beyond the crystallization paradigm: structure determination from diffraction
      patterns from ensembles of randomly oriented particles.
AB  - We amplify on the principles of the method we have recently proposed for
      recovering an oversampled diffraction pattern of a single particle from measured
      diffraction patterns from multiple particles in orientations related by rotation
      about an axis parallel to the incident radiation. We propose an alternative
      method of phasing a reference resolution ring by means of a non-negativity
      constraint on the diffraction intensities, point out the need for caution about
      enantiomeric ambiguities in the reconstruction of a diffraction pattern from its
      angular correlations, and show that converged correlations may be deduced by
      appropriate averaging of even very noisy data.

PMID- 21168273
TI  - Field emission techniques for studying surface reactions: applying them to NO-H2
      interaction with Pd tips.
AB  - The adsorption of NO and its reaction with H(2) over Pd tips were investigated by
      means of field ion microscopy (FIM) and pulsed field desorption mass spectrometry
      (PFDMS) in the 10(-3)Pa pressure range and at sample temperatures between 400 and
      600K. By varying the H(2) partial pressure while keeping the other control
      parameters constant, the NO+H(2) reaction over Pd crystallites is shown to
      exhibit a strong hysteresis effect. The hysteresis region narrows with increase
      in temperature and the H(2) pressures delimiting this hysteresis decrease as
      well. Abrupt transformations of the micrographs are observed by FIM from bright
      to dark patterns and vice versa. These transformations define the hysteresis
      region. The collected data allow establishing a novel kinetic phase diagram of
      the NO+H(2)/Pd system within the range of temperatures and pressures indicated.
      The observed features are correlated with a local chemical analysis by means of
      field pulses. NO(+) seems to be the dominating imaging species under all
      conditions. At high relative H(2) pressures (the "hydrogen-side"), H atoms seem
      to diffuse subsurface. This process is blocked at lower H(2) pressure (the "NO
      side") due to NO(ad) and O(ad) accumulation on the surface. Probe-hole
      measurements with field pulses indicate that the Pd surface undergoes oxidation
      as revealed by the occurrence of PdO(2)(+) species in the mass spectra.

PMID- 21168274
TI  - Investigation on Opisthorchis felineus occurrence and life cycle in Italy.
AB  - Opisthorchiasis is a fish borne parasitic infection caused by helminths of the
      genus Opisthorchis (Digenea, Opisthorchiidae), affecting humans and other fish
      eating mammals. Despite Opisthorchis felineus was first described in Italy in
      1884, no cases of human opisthorchiasis were reported in this country until 2004;
      from then on, 4 outbreaks due to this species have been recorded in Central
      Italy. Following the more relevant of these outbreaks, involving 34 people in
      August 2007, snails, fishes and fecal samples collected from the Bolsena and
      Bracciano lakes (Central Italy) were analyzed in order to define the cycle of O.
      felineus in the area and investigate its prevalence in the different hosts. Pools
      of 20-40 snails each (4983 specimens altogether) of the genus Bithynia were
      analyzed by PCR for parasite DNA detection. Eight hundred and ninety-four fish
      belonging to 12 species were collected from the two lakes and tested for
      metacercariae both by muscle compression and digestion techniques. Eighty-seven
      fecal samples of 5 putative definitive host species were collected very close to
      the two lakes and tested for parasite eggs detection by formalin-ethyl acetate
      concentration technique. Identification at the species level of metacercariae and
      eggs, respectively, from fish and stool was confirmed by PCR analysis and
      sequencing. O. felineus DNA was detected in 0.08% (overall minimum infection
      rate) of snails of the genus Bithynia from the two lakes. The tench, Tinca tinca,
      was the only fish found infested in both lakes (prevalence 88.5%). O. felineus
      eggs were found only in cat feces (prevalence 46.4%). The tench represents the
      only threat for the human consumption in the study area while Coregonus sp., the
      most economically important species for the local fishery and frequently consumed
      raw marinated, resulted to be not infected. The high prevalence recorded both in
      fish and in definitive host suggests a widespread and massive presence of the
      parasite in the area. Further studies are needed to better investigate the
      possible role of some cyprinids species as intermediate hosts, in order to check
      their safety for human consumption.

PMID- 21168275
TI  - The efficacy of milbemycin oxime against pre-adult Spirocerca lupi in
      experimentally infected dogs.
AB  - The aim of this investigation was to determine the efficacy of milbemycin oxime
      in preventing the oesophageal encapsulation of Spirocerca lupi, following the
      experimental infection of dogs. Two studies were conducted which involved a total
      of 21 purpose-bred Beagles. Each dog was infected with approximately 40, third
      stage infective S. lupi larvae. The larvae were dissected from scarabaeid beetles
      that had been collected from areas endemic for spirocercosis. In the first study,
      milbemycin oxime (minimum dose 0.5mg/kg body weight) was administered to seven
      dogs on day 30 post-infection. Seven other dogs served as untreated controls. In
      the second study, milbemycin oxime (also at a minimum dose of 0.5mg/kg body
      weight) was administered to four of seven infected dogs on day 28 post-infection.
      Treatment was repeated at 14- or 28-day intervals. All of the dogs, from both
      studies, were euthanized 168 or 169 days after infection. All S. lupi were
      recovered, and lesions in the thoracic aorta and oesophagus were described and
      quantified. A single treatment with milbemycin oxime was 79.8% effective in
      preventing the establishment of S. lupi in the oesophagus. This treatment
      significantly (p<0.05) reduced both the number of S. lupi within the oesophagus
      and the size of the oesophageal nodules. The efficacy of anthelmintic treatment
      was increased to 100% when repeat doses of milbemycin oxime were administered at
      14- or 28-day intervals. These repeat treatments completely prevented the
      establishment of S. lupi within the oesophagus and thereby averted the
      development of oesophageal nodules. As expected, none of the treatment protocols
      reduced S. lupi related damage within the aorta because the administration of
      milbemycin oxime only began after the larvae had completed their first stage of
      migration.

PMID- 21168276
TI  - Prevalence of Sarcocystis spp. in Argentinean cattle.
AB  - Sarcocystis cruzi, S. hirsuta and S. hominis are apicomplexan parasites that
      affect cattle worldwide with variable prevalence. The aim of the present study
      was to evaluate the prevalence of Sarcocystis spp. in Argentinean cattle
      comparing microscopic fresh examination and molecular methods. Blood, myocardium
      and loin samples were collected in five slaughterhouses from a total of 380
      bovines. Origin of animals was representative of the major beef cattle production
      area of Argentina. Samples were analyzed by fresh microscopical examination,
      transmission electron microscopy (TEM), IFAT and PCR-RFLP. Thin walled sarcocysts
      corresponding with S. cruzi were found in 99.5% of heart samples. Sarcocysts were
      detected in 73.1% of loin samples; 71.5% had S. cruzi cysts and 23.1% had thick
      walled sarcocysts (S. hirsuta or S. hominis). TEM observation revealed the
      presence of characteristic S. hominis and S. hirsuta cyst walls in 7 and 1 loin
      samples respectively. Using IFAT, 379/380 animals had titers 25 or higher,
      showing a full agreement with fresh examination. Amplification products were
      detected in 35.5% (135/380) of loin samples; however Sarcocystis species could
      only be determined by RFLP in 29 samples. Agreement between fresh examination and
      PCR was low (Kappa value=0.262). This is the first report of S. hominis and S.
      hirsuta in Argentina. Further studies are needed to improve the sensitivity of
      molecular methods for species identification, especially for differentiation of
      S. cruzi and S. hirsuta from the zoonotic species S. hominis. The results of the
      present study and others focusing on sensitivity and specificity of Sarcocystis
      spp. diagnostic methods should contribute to improve food safety.

PMID- 21168277
TI  - Light and scanning electron microscopy of sporocysts of Eurytrema coelomaticum
      (Giard et Billet, 1892) Looss, 1907.
AB  - Eurytrema coelomaticum is a fluke that infects ruminants in South America, Europe
      and Asia. The morphology of the mother and daughter sporocysts of E. coelomaticum
      obtained from Bradybaena similaris, the first intermediate host, is described for
      the first time by light and scanning electron microscopy. The intermediate host
      was exposed to E. coelomaticum eggs and after 30 days the mother sporocyst was
      found in the coelom adhered to the intestine wall. This sporocyst was a rounded
      or elongated mass (0.1078 mm), with numerous germinal balls in it, and a folded
      tegument with no specializations. The daughter sporocysts obtained following
      dissection of infected snails have varied shape, one hollow tapered region with
      many transversal and longitudinal striations, named anterior end. The expelled
      daughter sporocyst presented an oval sac-like central region with a small
      anterior and a posterior longer filament-like prolongation. The measures of the
      expelled sporocysts are presented and compared to previous descriptions.

PMID- 21168278
TI  - Development of an indirect ELISA-NcSRS2 for detection of Neospora caninum
      antibodies in cattle.
AB  - Neosporosis is of alarming economic concern in the cattle industry. The
      effectiveness of diagnostic tests for detecting specific antibodies against
      Neospora caninum is hampered by potential cross-reaction with other coccidia. Use
      of a single specific antigen might improve test specificity. An indirect enzyme
      linked immunosorbent assay (ELISA) was developed using the truncated protein
      NcSRS2 expressed in Escherichia coli. The ELISA results were compared with those
      of the indirect fluorescence antibody test (IFAT). Receiver Operating
      Characteristic (ROC) and Tests in the Absence of a Gold Standard (TAGS) analysis
      revealed an assay having 96% specificity and 95% sensitivity when applied to 145
      positive and 352 negative sera from two distinct cattle populations. Using OD <=
      0.095 as the cut-off point, the assay's negative and positive predictive values
      ranged from 98.8% to 50.8% and from 58.8% to 99.1%, respectively, depending on
      neosporosis prevalence in a given area. The novel ELISA-NcSRS2 format described
      in the present report constitutes a specific and sensitive method for detecting
      N. caninum in cattle.

PMID- 21168279
TI  - Nematode infection in fish from Cartagena Bay, North of Colombia.
AB  - Parasitic nematode infection indices were recorded in different fish species
      collected at Cartagena Bay, North of Colombia. Among 19 studied species, the
      Mugil genus presented the highest prevalence (83.9-100%), although Sciades
      herzbergii, Caranx hippos and Centropomus undecimalis were also found infected
      with nematodes. Parasites were found in the liver, intestinal mesenteries and
      encysted near the intervertebral joints, with an average parasite abundance of
      4.0 +/- 0.3 nematodes per fish. Morphological analysis allowed the identification
      of these nematodes as Contracaecum sp. A small, but positive correlation was
      found between parasite abundance and length (R=0.294, P<0.001) and weight
      (R=0.244, P<0.001). In contrast, the correlation between parasite abundance and
      condition factor was negative (R=-0.191, P<0.001). These results are the first
      describing the presence of nematodes in several fish species of this ecosystem,
      and it highlights the need for monitoring parasitism in Mugil species in order to
      avoid parasite ingestion during fish consumption.

PMID- 21168280
TI  - Combating melanoma: the use of photodynamic therapy as a novel, adjuvant
      therapeutic tool.
AB  - Metastatic malignant melanoma remains one of the most dreaded skin cancers
      worldwide. Numerous factors contribute to its resistance to hosts of treatment
      regimes and despite significant scientific advances over the last decade in the
      field of chemotherapeutics and melanocytic targets, there still remains the need
      for improved therapeutic modalities. Photodynamic therapy, a minimally invasive
      therapeutic modality has been shown to be effective in a number of oncologic and
      non-oncologic conditions. Using second-generation stable, lipophilic
      photosensitizers with optimised wavelengths, PDT may be a promising tool for
      adjuvant therapy in combating melanoma. Potential targets for PDT in melanoma
      eradication include cell proliferation inhibition, activation of cell death and
      reduction in pro-survival autophagy and a decrease in the cellular melanocytic
      antioxidant system. This review highlights the current knowledge with respect to
      these characteristics and suggests that PDT be considered as a good candidate for
      adjuvant treatment in post-resected malignant metastatic melanoma. Furthermore,
      it suggests that primary consideration must be given to organelle-specific
      destruction in melanoma specifically targeting the melanosomes - the one
      organelle that is specific to cells of the melanocytic lineage that houses the
      toxic compound, melanin. We believe that using this combined knowledge may
      eventually lead to an effective therapeutic tool to combat this highly
      intractable disease.

PMID- 21168281
TI  - Increased morning adrenocorticotrophin hormone (ACTH) levels in women with
      postpartum thoughts of harming the infant.
AB  - INTRODUCTION: Some postpartum women experience intrusive thoughts of harming the
      infant. The hypothalamic-pituitary-adrenal (HPA) axis, which has been linked to
      postpartum depression, may play a role in the aetiology of postpartum thoughts of
      harming the infant. We aimed to study whether HPA axis hormones measured early
      postpartum are related to postpartum intrusive thoughts. METHOD: 132 women who
      delivered a child at a university hospital participated in a follow-up study with
      visits at 2-3 days postpartum and 8th week postpartum. Participants were assessed
      for trait anxiety, social support, peripartum or postpartum anxiety or
      depression, stressful life events and obstetric variables including perinatal
      complications and lactation. Postpartum thoughts of harming the infant were
      assessed with a semi-structured interview. Serum cortisol, and plasma CRH and
      ACTH levels were measured within 48 h postpartum at 8-9 AM. A logistic regression
      was performed to explore the relationship between clinical variables, hormonal
      measures and postpartum intrusive thoughts. RESULTS: Patients with postpartum
      thoughts of harming the infant had, when compared to those women without
      intrusive thoughts, higher ACTH levels (7.59 pmol/L vs 5.09 pmol/L, p<0.05)
      without significant differences in CRH or cortisol levels. In the logistic
      regression analysis, adjusted for breast-feeding and psychopathological status,
      only ln ACTH was associated with the presence of postpartum thoughts of harming
      the infant (OR=5.2, CI 95% 1.2-22.6, p=0.029). No other clinical variables were
      associated with postpartum intrusive thoughts. CONCLUSIONS: Our study suggests
      that a dysregulation of the hypothalamic-pituitary-adrenal axis may play a role
      in the aetiology of postpartum thoughts of harming the infant.

PMID- 21168282
TI  - Stereotactic irradiation of the postoperative resection cavity for brain
      metastasis: a frameless linear accelerator-based case series and review of the
      technique.
AB  - PURPOSE: Whole-brain radiation therapy (WBRT) is the standard of care after
      resection of a brain metastasis. However, concern regarding possible
      neurocognitive effects and the lack of survival benefit with this approach has
      led to the use of stereotactic radiosurgery (SRS) to the resection cavity in
      place of WBRT. We report our initial experience using an image-guided linear
      accelerator-based frameless stereotactic system and review the technical issues
      in applying this technique. METHODS AND MATERIALS: We retrospectively reviewed
      the setup accuracy, treatment outcome, and patterns of failure of the first 18
      consecutive cases treated at Brigham and Women's Hospital. The target volume was
      the resection cavity without a margin excluding the surgical track. RESULTS: The
      median number of brain metastases per patient was 1 (range, 1-3). The median
      planning target volume was 3.49 mL. The median prescribed dose was 18 Gy (range,
      15-18 Gy) with normalization ranging from 68% to 85%. In all cases, 99% of the
      planning target volume was covered by the prescribed dose. The median conformity
      index was 1.6 (range, 1.41-1.92). The SRS was delivered with submillimeter
      accuracy. At a median follow-up of 12.7 months, local control was achieved in
      16/18 cavities treated. True local recurrence occurred in 2 patients. No marginal
      failures occurred. Distant recurrence occurred in 6/17 patients. Median time to
      any failure was 7.4 months. No Grade 3 or higher toxicity was recorded. A long
      interval between initial cancer diagnosis and the development of brain metastasis
      was the only factor that trended toward a significant association with the
      absence of recurrence (local or distant) (log-rank p = 0.097). CONCLUSIONS:
      Frameless stereotactic irradiation of the resection cavity after surgery for a
      brain metastasis is a safe and accurate technique that offers durable local
      control and defers the use of WBRT in select patients. This technique should be
      tested in larger prospective studies.

PMID- 21168283
TI  - Radiosensitizing properties of bortezomib depend on therapeutic schedule.
AB  - PURPOSE: To investigate the influence of the bortezomib (BTZ) on malignant glioma
      radiosensitivity in two xenograft models. METHODS AND MATERIALS: For TCG3 and U87
      models, we evaluated the antitumor activity of BTZ, radiotherapy, and BTZ plus
      radiothearapy according to two therapeutic schedules: a "nonfractionated"
      schedule corresponding to a single dose of treatment per week, and a
      "fractionated" schedule corresponding to the same weekly dose divided into 5
      fractions. Treatments influence on proliferation and apoptosis indexes, cell
      cycle distribution, and nuclear factor-kappaB pathway were explored. RESULTS: The
      radiosensitizing properties of BTZ observed with the nonfractionated schedule
      were lost with the fractionated schedule. Bortezomib-mediated radiosensitization
      was associated with an increased apoptosis response and major changes in cell
      proliferation, but the nuclear factor-kappaB pathway was not involved. Most of
      the cellular effects induced by BTZ when tumors received a single irradiation
      were cancelled out if radiotherapy was fractionated. CONCLUSION: The influence of
      BTZ on glioma radiosensitivity seems to depend on the treatment fractionation
      schedule, emphasizing the need to clarify the mechanisms underlying BTZ's
      radiosensitizing effects before further clinical trials are initiated.

PMID- 21168284
TI  - Long-term outcomes in patients with isolated supraclavicular nodal recurrence
      after mastectomy and doxorubicin-based chemotherapy for breast cancer.
AB  - PURPOSE: To examine the outcome of patients who developed an isolated
      locoregional recurrence (LRR) involving the supraclavicular fossa (SCV) after
      initial treatment with modified radical mastectomy and chemotherapy. METHODS AND
      MATERIALS: Records from 140 breast cancer patients treated on five prospective
      trials with mastectomy and doxorubicin-based chemotherapy, with or without
      radiation, who developed a LRR were reviewed. Kaplan-Meier survival times were
      calculated using date of LRR as time zero. RESULTS: The median follow-up after
      LRR was 2.9 years (N = 140; interquartile range, 1.3-6.6 years). In all, 47 of
      140 patients (34%) had an SCV component to their LRR. These patients had lower 3
      y distant metastasis-free survival (40% vs. 54%, p = 0.003) and overall survival
      (49% vs. 69%, p = 0.04) than patients without an SCV component. Multivariate
      analysis revealed that LRR involving an SCV component (hazard ratio, 1.96, p =
      0.004) and patients with lymphovascular space invasion in their primary tumors
      (hazard ratio, 1.65, p = 0.029) were independently associated with a poor distant
      metastasis-free survival. However, among 23 patients with isolated SCV
      recurrence, Overall survival was not statistically significantly different
      between isolated chest wall recurrence and isolated SCV recurrence. Patients with
      isolated SCV recurrence displayed a median follow-up of 3.3 years (IR, 1.2-5.2).
      Only 6 LRR of 23 patients were treated with aggressive local therapy, including
      surgery, chemotherapy, and radiation (alone or in combination). CONCLUSIONS:
      Although breast cancer recurrence with SCV involvement carries a high risk of
      distant metastasis and death, among women with recurrence limited to the SCV
      alone, overall survival after isolated SCV recurrence can be long (25% >5 years).

PMID- 21168285
TI  - Borrelia burgdorferi sensu lato in sheep keds (Melophagus ovinus), Tibet, China.

PMID- 21168286
TI  - Characterization of chicken egg yolk immunoglobulins (IgYs) specific for the most
      prevalent capsular serotypes of mastitis-causing Staphylococcus aureus.
AB  - The objective of this in vitro study was to evaluate the potential of egg yolk
      immunoglobulins (IgYs) for treating mastitis caused by Staphylococcus aureus.
      Specific IgY against type 5 (IgY-T5), type 8 (IgY-T8) and type 336 (IgY-T336) S.
      aureus strains were obtained by immunizing hens with whole cell vaccines and the
      IgY produced were then purified to around 80% purity using a water dilution
      method coupled with salting out and ultra-filtration. Enzyme-linked immunosorbent
      assay indicated that the IgY specifically targeted the three homologous strains.
      A growth inhibition assay was performed in Columbia broth (non-encapsulated form)
      and phosphate-buffered saline (encapsulated form) for an 8h incubation. The
      results showed that IgY-T336 significantly inhibited (but only 1.5 log units;
      P<0.01) the growth of all three strains at 15 mg/ml in the Columbia broth. In
      contrast, the same concentrations of IgY-T5 and IgY-T8 did not show obvious
      bacteriostatic activity against the two homologous strains. In phosphate buffered
      saline, no inhibition of the two encapsulated strains was observed with IgY-T5,
      IgY-T8 and IgY-T336. However, IgY-T336 reduced live bacteria by 1.0 log unit
      against strain 336 compared with the control. An internalization test indicated
      that all of the specific IgY (at 5mg/ml) significantly (about 3.0 log units of
      the control; P<0.01) blocked the internalization of their homologous strains by
      bovine mammary epithelial cells (MAC-T cells) within 6h. These results suggested
      that research on the application of IgY as a treatment for mastitis caused by S.
      aureus should be focused on the internalization inhibition activity rather than
      on the growth inhibition activity of the IgY.

PMID- 21168287
TI  - In vitro susceptibility of canine and feline Escherichia coli to fosfomycin.
AB  - Therapeutic options for multi-drug resistant (MDR) Escherichia coli in dogs or
      cats are limited. The objective of this study was to establish in vitro
      susceptibility of canine and feline E. coli to fosfomycin. Two sources of
      isolates were categorized based on susceptibility as to no resistance (NDR),
      single drug resistance (SDR), multidrug resistance (MDR) or extreme drug
      resistance (XDR). Clinical isolates were collected from throughout the US from
      dogs (n=157) or cats (n=43) with naturally occurring infection between March 2008
      and January 2010. Experimental isolates were collected from fecal samples of dogs
      treated with no drug (NDR), amoxicillin (expressing SDR) or enrofloxacin
      (expressing MDR or XDR). Fosfomycin minimum inhibitory concentrations (MIC) were
      determined using E-Test((r)). For clinical isolates, most (165/200) originated
      from the urinary tract, with the number of isolates per resistant category being:
      NDR (N=44, 22%), SDR (N=65, 32.5%), MDR (N=74, 37%), and XDR (N=17, 8.5%). Of
      these isolates, 99% (197/200) were susceptible to fosfomycin with the MIC(90) and
      MIC(50) being 2 and 1 MUg/ml, respectively (range: 0.25-196 MUg/ml). The number
      of experimental isolates in each category was NDR (3), SDR (23), MDR (38), and
      XDR (11) (29.3, 44, and 14.7%, respectively). Of these, 100% were susceptible to
      fosfomycin with MIC(90) and MIC(50) being 1.5 and 1 MUg/ml (range: 0.38-4
      MUg/ml), respectively. The susceptibility of canine and feline MDR and XDR E.
      coli to fosfomycin at concentrations well below the susceptible breakpoint
      supports further investigation for its use when treating E. coli resistant to
      alternative antimicrobials.

PMID- 21168288
TI  - Comparison of two sampling methods for microbiological evaluation of periodontal
      disease in cats.
AB  - BACKGROUND: Periodontal disease in cats is highly prevalent, and its aetiology is
      associated to bacteria located in the subgingival microbiota, being Porphyromonas
      sp. the most prevalent genus. The conventional technique to sample the
      subgingival microbiota is the use of cotton swabs over the mucosa and teeth;
      however the use of subgingival paper points could improve the bacterial recovery.
      AIM: The objective was to compare two microbial sampling approaches for the
      evaluation of the periodontal disease-associated microflora in cats. METHODS: The
      study was designed as a pilot study. Ten cats were clinically evaluated and
      sampled under sedation. Subgingival pooled samples were collected from four
      sites. In parallel, samples were obtained with a cotton swab, by striking over
      the gingival margin and surface of the upper right canine. Samples were cultured
      on blood agar (aerobic and anaerobic incubation), Dentaid-1 (for Aggregatibacter
      actinomycetemcomitans and enterics), and a specific medium for Bartonella
      henselae. RESULTS: For total anaerobic counts, paper point samples (6.59 +/- 0.5)
      demonstrated significantly higher counts (p=0.03) than cotton swab samples (5.54
      +/- 1.1). Moreover, the use of paper points increased the frequency detection of
      most pathogens thus reducing false negatives for Porphyromonas gulae (100% with
      paper points samples and 80% with cotton swab samples). CONCLUSIONS: Significant
      higher recoveries of anaerobic bacteria and more frequent detection of putative
      periodontal pathogens was observed when microbiological sampling was performed
      with paper points, in cats with periodontal disease.

PMID- 21168289
TI  - TERC telomerase subunit gene copy number in placentas from pregnancies
      complicated with intrauterine growth restriction.
AB  - INTRODUCTION: intrauterine growth restriction (IUGR) is a significant cause of
      both short- and long-term morbidity and mortality. IUGR secondary to placental
      dysfunction is correlated with telomere shortening. Telomerase is an enzyme
      complex that elongates telomeres. One of its components is encoded by the
      telomerase RNA component gene (TERC), which serves as the RNA template for the
      addition of telomeric repeats. We hypothesized decreased TERC gene copy number in
      IUGR placentas as part of the mechanism of telomere shortening in placental
      dysfunction. METHODS: we estimated the gene copy number of the TERC gene at 3q26
      by applying FISH to trophoblasts of placental biopsies from five pregnancies with
      IUGR caused by placental insufficiency and compared them to placentas from five
      gestational-age matched, uncomplicated pregnancies. RESULTS: significantly lower
      TERC gene copy number was observed in IUGR trophoblasts on the same chromosome
      and on other chromosomes, compared to the control samples (p<0.05). CONCLUSIONS:
      the TERC gene copy number is decreased in IUGR trophoblasts. These results
      support the observations of telomere shortening and decreased telomerase activity
      in IUGR placentas. We suggest that these findings might play a role in the
      pathophysiology of IUGR, perhaps by promoting senescence in trophoblasts of IUGR
      placentas.

PMID- 21168290
TI  - Bacteria in bovine semen can increase sperm DNA fragmentation rates: a kinetic
      experimental approach.
AB  - Cryopreserved straws of semen (n=228) from Holstein bulls (n=47) were examined
      for bacterial presence and sperm DNA fragmentation (SDF) dynamics. Commercial
      semen doses (representing six ejaculates per individual) were randomly selected
      from a bull stud in Spain. The dynamics of SDF were assessed after thawing (T0)
      and at 4, 24, 48, 72 and 96h of incubation at 37 degrees C, using the commercial
      variant of the sperm chromatin dispersion test for Bovine (Halomax(r)). One group
      of bulls showed a bacterial presence in semen samples between 0 and 96h of
      incubation (n=23, group A) while the other did not (n=24, group B). Immediate
      post-thaw differences in SDF were not observed when both groups were compared.
      However, the rate of increase in SDF (rSDF) over time, considered as an estimate
      of the kinetic behaviour of sperm DNA survival, was significantly higher (P<0.05)
      in semen samples from group A (0.7% per hour) versus group B (0.05% per hour).
      Polymerase Chain Reaction (PCR) assay was used for DNA amplification using
      primers designed for specific regions of the bacterial gene that codifies for 16S
      rRNA. Different species within the phyla Bacteroidetes, Firmicutes,
      Proteobacteria, Cyanobacteria, Fusobacteria and Actinobacteria were identified.
      The results show that (1) SDF at baseline (T0) may not be affected by the
      presence of bacteria but the rSDF can increase due to bacterial growth during
      incubation, (2) the increase in the rSDF is characteristic of some bulls but not
      for others, and (3) certain bacterial strains are repeatedly found in separate
      ejaculates from the same bull.

PMID- 21168291
TI  - Concomitant use of prescription medications and dietary supplements in menopausal
      women: an approach to provider preparedness.
AB  - Dietary supplements are becoming increasingly popular as therapies for symptom
      relief among menopause-age women in the United States. However, a large gap
      exists between research in the concomitant use of prescription medications and
      dietary supplements and provider preparedness to guide patient decision making.
      Many menopausal women take prescription medications, over the counter
      medications, and herbs and dietary supplements for climactic symptoms or other
      health conditions. With any drug, there is the potential for interactions. Women
      taking medications with a narrow therapeutic index, such as anticoagulants,
      anticonvulsants, and drugs for the treatment of chronic diseases, are at
      particular risk. Patients should be queried regarding their use of dietary
      supplements when starting or stopping a prescription drug, or if unexpected
      reactions occur. When counseling patients, one must carefully consider the risks
      and benefits of each supplement and medication being taken by each individual.

PMID- 21168292
TI  - What women want? Exercise preferences of menopausal women.
AB  - BACKGROUND: Many menopausal women are keen to find alternatives to HRT; exercise
      might be useful in this regard but more trial evidence is required. Before we
      conduct such trials however, it is important to understand the exercise
      preference of these women so that appropriate exercise interventions can be
      developed for inclusion in such trials. AIM: To investigate the exercise
      preferences of menopausal women and to examine the association between exercise
      levels, BMI, and hot flushes/night sweats in this population. METHOD:
      Participants were women aged 46-55 years from eight diverse general practices in
      Birmingham. A postal questionnaire containing items about demographics, lifestyle
      behaviours, weight, height, menopausal status, frequency of hot flushes/night
      sweats and preferences for exercise was sent to all eligible women. RESULTS:
      1693/2776 (61.0%) of women replied. The majority (75.9%) of respondents stated
      that exercise was an acceptable intervention. The most commonly chosen option for
      delivery of exercise interventions was by one-to-one consultations with a fitness
      advisor, followed by DVD sent by post. Telephone based interventions and e-Health
      interventions (i.e. Internet and mobile phone text messages) were the
      interventions least chosen. There was also an overwhelming choice for walking as
      a mode of exercise. A series of two factor analyses of covariance indicated
      exercise participation and BMI were not significantly related to frequency of hot
      flushes/night sweats in symptomatic menopausal women. CONCLUSION: Menopausal
      women have strong preferences to receive exercise interventions that involve one
      to-one contact with a fitness advisor or by exercise DVD. The use of more recent
      technology to deliver exercise interventions was highly unpopular. These findings
      should be considered in future studies when planning exercise interventions with
      this population.

PMID- 21168293
TI  - A mouse's tail: how to settle an insurance dispute.
AB  - Over the last years insurance companies have shown an increased interest in
      identifications of pest species, either as a form of risk assessment or to
      address liability issues. This paper describes a case report of such a forensic
      insurance investigation. The names of the corporations involved have been
      withheld in compliance with a pre-existing confidentiality agreement. A sea
      container containing sterile goods was shipped from China to the Netherlands.
      Upon inspection at its final destination, the contents were declared lost due to
      the presence of a dead mouse. Determination of which company should be held
      liable for this loss depended on where the mouse entered the container. The
      specimen was identified as belonging to the genus Apodemus (Muridae) based on
      morphology. Two species, A. sylvaticus and A. flavicollis occur in the
      Netherlands, two different species, A. agrarius and A. draco, occur in the
      relevant area in Eastern China. The distribution areas of these Dutch and Chinese
      Apodemus species do not overlap. Because the specimen was adolescent and partly
      mummified, key morphological characters for species-level identification were
      missing or not discernable. Published literature and sequence data available on
      GenBank showed that the four candidate species could be distinguished based on
      Cytochrome B barcode sequences. Given the decayed condition of the specimen, we
      expected possible DNA degradation. Therefore, both internal Cyt B primers
      (designed to amplify a short nucleotide sequence) and universal primers (which
      amplify a fourfold larger fragment) were employed. Remarkably, the primerset that
      was designed to amplify a short Cyt B sequence of A. draco amplified a well
      studied pseudogene of A. sylvaticus. Both the Cyt B and the pseudogene sequence
      confirmed that the specimen in question is A. sylvaticus. Contamination of the
      sterile goods must therefore had taken place in the Netherlands.

PMID- 21168294
TI  - Striation patterns in serrated blade stabs to cartilage.
AB  - Stab wounds were made in porcine cartilage with 13 serrated knives, amongst which
      4 were drop-point and 9 straight-spine; 9 coarsely serrated, 3 finely serrated
      and 1 with mixed pattern serrations. The walls of the stab tracks were cast with
      dental impression material, and the casts photographed together with the knife
      blades for comparison. All 13 serrated blades produced an "irregularly regular"
      pattern of striations on cartilage in all stabbings. Unusual and distinctive
      blade serration patterns produced equally distinctive wound striation patterns. A
      reference collection of striation patterns and corresponding blades might prove
      useful for striation pattern analysis. Drop-point blades produced similar
      striations to straight-spine blades except that the striations were not parallel
      but rather fan-shaped, converging towards the wound exit. The fan-shaped
      striation pattern characteristic of drop-point blades is explained by the initial
      lateral movement of the blade through the cartilage imposed by the presence of
      the drop point shape. It appears that the greater the overall angle of the drop
      point, the shorter the blade length over which the drop point occurs, and the
      closer the first serration is to the knife tip, the more obvious is the fan
      shaped pattern. We anticipate that micro-irregularities producing individualising
      characteristics in non-serrated drop point blades, provided they were located at
      the tip opposite the drop point, should also show a fan-shaped pattern indicative
      of a drop point blade. The examination of the walls of stab wounds to cartilage
      represents an under-utilised source of forensic information to assist in knife
      identification.

PMID- 21168295
TI  - Preoperative imaging study of the spinal cord vascularization: interest and
      limits in spine resection for primary tumors.
AB  - The necessicity to localize the anterior spinal arteries before anterior approach
      of the spine stays controversial by orthopaedic surgeons. On the other hand the
      surgical treatment of thoracoabdominal aneurisms routinely sacrifices many
      segmental arteries pairs without spinal arteries localization. This, associated
      with spinal cord protection, results to few neurological complication. However,
      during vertebrectomies, the roots ligation completely interrupts the spinal cord
      blood supply at this level. In our experience the spinal arteries localization
      was systematically done before ninety-eight spine resections. In five cases an
      anterior radiculomedullary artery was ligated (four anterior radiculomedullary
      and one great anterior radiculomedullary arteries) without neurological
      complication, in two cases of extended resection (more than four levels) a
      neurological complication occurred. No spinal artery was identified at the
      resection level and the neurological complications were resolutive and did not
      seem related to definitive vascular problem. These accomplishments lead to
      discuss the importance of spinal arteries localization and preservation in this
      surgery. The discovery of an anterior radiculomedullary artery is not a
      contraindication to en-bloc vertebrectomy at this level, nevertheless in the case
      of great anterior radiculomedullary artery (Adamkiewicz) the surgical indication
      must be seriously debated. In fact, this case and those where multilevel
      resections (more than three levels) are indicated seem the most dangerous
      situations and the use of the different means of spinal cord protection could be
      indicated to decrease neurological risk. So before spine resection the spinal
      arteries localization could improve patient information and give more deciding
      factors for planning treatment.

PMID- 21168296
TI  - Imaging of the hand.

PMID- 21168297
TI  - Bioanalytical method development and validation of natamycin in rabbit tears and
      its application to ocular pharmacokinetic studies.
AB  - A new selective and sensitive high-performance liquid chromatography coupled with
      tandem mass spectrometry (LC-MS/MS) method was developed for the quantification
      of natamycin in rabbit tears using amphotericin B as internal standard (IS).
      Chromatographic separation was achieved on a Luna Cyano column (100 mm * 2 mm, 3
      MUm) using ammonium acetate buffer (pH 4; 3.5mM): methanol (10:90, v/v) as the
      mobile phase. The run time was 5 min. Detection was performed by negative ion
      electrospray ionization in multiple reaction monitoring (MRM) mode. The
      calibration curve was linear over the concentration range from 25 to 800 ng/ml,
      and lower limit of detection of 12.5 ng/ml. The accuracy and precision of the
      method were within the acceptable limit of +/- 20% at the lower limit of
      quantitation and +/- 15% at other concentrations. Natamycin was stable during the
      battery of stability studies viz., bench-top, auto-sampler, freeze/thaw cycles
      and 30 days storage in a freezer at -70 +/- 10  degrees C. The method was
      successfully applied to the ocular pharmacokinetic studies of natamycin eye drops
      in New Zealand rabbit tears.

PMID- 21168298
TI  - Development and evaluation of a multiple-plate fraction collector for sample
      processing: application to radioprofiling in drug metabolism studies.
AB  - Microplate scintillation counters are utilized routinely in drug metabolism
      laboratories for the off-line radioanalysis of fractions collected during HPLC
      radioprofiling. In this process, the current fraction collection technology is
      limited by the number of plates that can be used per injection as well as the
      potential for sample loss due to dripping or spraying as the fraction collector
      head moves from well to well or between plates. More importantly, sample
      throughput is limited in the conventional process, since the collection plates
      must be manually exchanged after each injection. The Collect PAL, an innovative
      multiple-plate fraction collector, was developed to address these deficiencies
      and improve overall sample throughput. It employs a zero-loss design and has sub
      ambient temperature control. Operation of the system is completely controlled
      with software and up to 24 (96- or 384-well) fraction collection plates can be
      loaded in a completely automated run. The system may also be configured for
      collection into various-sized tubes or vials. At flow rates of 0.5 or 1.0 mL/min
      and at collection times of 10 or 15s, the system precisely delivered 83-MUL
      fractions (within 4.1% CV) and 250-MUL fractions (within 1.4% CV), respectively,
      of three different mobile phases into 12 mm * 32 mm vials. Similarly, at a flow
      rate of 1 mL/min and 10s collection times, the system precisely dispensed mobile
      phase containing a [(14)C]-radiolabeled compound across an entire 96-well plate
      (% CV was within 5.3%). Triplicate analyses of metabolism test samples containing
      [(14)C]buspirone and its metabolites, derived from three different matrices
      (plasma, urine and bile), indicated that the Collect PAL produced radioprofiles
      that were reproducible and comparable to the current technology; the % CV for 9
      selected peaks in the radioprofiles generated with the Collect PAL were within
      9.3%. Radioprofiles generated by collecting into 96- and 384-well plates were
      qualitatively comparable; however, the peak resolution was greater in the
      profiles that were collected in 384-well plates due to the collection of a larger
      number of fractions per minute. In conclusion, this new and innovative fraction
      collector generated radioprofile results that were comparable to current
      technology and should provide a major improvement in capacity and throughput for
      radioprofiling studies.

PMID- 21168299
TI  - A validated ultra high pressure liquid chromatographic method for qualification
      and quantification of folic acid in pharmaceutical preparations.
AB  - A fully validated UHPLC method for the identification and quantification of folic
      acid in pharmaceutical preparations was developed. The starting conditions for
      the development were calculated starting from the HPLC conditions of a validated
      method. These start conditions were tested on four different UHPLC columns: Grace
      Vision HTTM C18-P, C18, C18-HL and C18-B (2 mm * 100 mm, 1.5 MUm). After
      selection of the stationary phase, the method was further optimised by testing
      two aqueous and two organic phases and by adapting to a gradient method. The
      obtained method was fully validated based on its measurement uncertainty
      (accuracy profile) and robustness tests. A UHPLC method was obtained for the
      identification and quantification of folic acid in pharmaceutical preparations,
      which will cut analysis times and solvent consumption.

PMID- 21168301
TI  - Differences in voluntary ethanol consumption in Wistar rats from five different
      suppliers.
AB  - Understanding the mechanism of action of ethanol and the neurobiological
      substrates for alcohol use disorders is challenging. In search of this knowledge,
      it is imperative to use valid animal experimental models. The Wistar rat is one
      example of a commonly used strain that also exert foundation stock for several
      rat lines selectively bred for high and low voluntary ethanol intake. Different
      studies report varying ethanol intake in Wistar rats posing the question of
      whether this is because of the methodological differences or the rat strain. The
      purpose of this study was therefore to compare voluntary ethanol intake in Wistar
      rats from five different suppliers. Rats from B&K Universal, UK (BK); Charles
      River, Germany; Harlan Laboratories, IN (Hsd); Harlan Laboratories, The
      Netherlands (RccHanTM); and Taconic, Denmark were exposed to a three-bottle free
      choice paradigm with intermittent 24 h access to 5 and 20% ethanol and water
      three times per week for 6 weeks. A general finding was that the RccHanTM rats
      differed significantly from the other groups. At the end of the experiment, the
      RccHanTM group had the highest median ethanol intake of 3.85 g/kg/24 h, whereas
      the BK rats had the lowest intake of 1.84 g/kg/24 h. The preference for ethanol
      was also different throughout the experiment. At the end of the experiment, the
      RccHanTM rats had the highest preference of approximately 80%, whereas the BK
      rats had the lowest preference around 25%. During the 6-week drinking period,
      only the Hsd rats increased their ethanol intake, as evidenced by a significant
      increase of 5% ethanol intake. Although all rats are of Wistar origin, they
      display profound differences in voluntary ethanol consumption depending on the
      supplier. The choice of Wistar can therefore have implications for the outcome
      and make comparisons between studies difficult. The present findings highlight
      the supplier as an important parameter to consider when planning and performing
      preclinical animal studies in the field of alcohol research.

PMID- 21168300
TI  - Are primary health care providers prepared to implement an anti-smoking program
      in Syria?
AB  - OBJECTIVE: To document primary health care (PHC) providers' tobacco use, and how
      this influences their smoking cessation practices and attitudes towards tobacco
      control policies. METHODS: Anonymous questionnaires were distributed to PHC
      providers in 7 randomly selected PHC centers in Aleppo, Syria. RESULTS: All PHC
      providers completed the questionnaires (100% response rate). A quarter of these
      providers smoke cigarettes and more than 10% smoke waterpipes. Physicians who
      smoke were less likely to advise patients to quit (OR=0.29; 95% CI, 0.09-0.95),
      assess their motivation to quit (OR=0.13, 95% CI=0.02-0.72), or assist them in
      quitting (OR=0.24, 95% CI=0.06-0.99). PHC providers who smoke were less likely to
      support a ban on smoking in PHC settings (68.2% vs. 89.1%) and in enclosed public
      places (68.2% vs. 86.1%) or increases in the price of tobacco products (43.2% vs.
      77.4%) (P<0.01 for all comparisons). CONCLUSIONS: Smoking, including waterpipe,
      continues to be widespread among PHC providers in Syria and will negatively
      influence implementation of anti-smoking program in PHC settings. PRACTICE
      IMPLICATIONS: Smoking awareness and cessation interventions targeted to PHC
      providers, and training programs to build providers' competency in addressing
      their patients' smoking is crucial in Syria.

PMID- 21168303
TI  - Knee stability after posterior cruciate ligament reconstruction in female versus
      male patients: a prospective matched-group analysis.
AB  - PURPOSE: To analyze outcome differences after posterior cruciate ligament (PCL)
      reconstruction in male and female patients. METHODS: A prospective database of
      234 PCL reconstructions (53 female and 181 male patients) with either isolated or
      combined procedures was analyzed. Patients were followed up for a mean of 62
      months (range, 34 to 110 months) by use of stress radiography and the
      International Knee Documentation Committee score. We included 32 female patients
      for a matched-group analysis and compared them with 32 matching male patients.
      Matching parameters were number/type of reconstructed ligaments, revision/primary
      surgery, autograft/allograft use, preoperative tibial displacement, time interval
      from injury to surgery, follow-up interval, and age. RESULTS: There was no
      preoperative difference in posterior stress radiographs (12.9 +/- 3.0 mm in
      female patients and 13.2 +/- 2.3 mm in male patients). After surgery, both groups
      showed a significant reduction in posterior displacement (6.0 +/- 2.5 mm [54%
      reduction] in female patients and 7.8 +/- 2.2 mm [40% reduction] in male
      patients). There was a significant greater reduction of posterior laxity in
      female patients. International Knee Documentation Committee scoring showed a
      significant improvement in both groups. CONCLUSIONS: We found in this specific
      patient series a superior reduction of posterior tibial laxity in female patients
      compared with male patients, indicating that possible gender-related differences
      exist after PCL surgery. LEVEL OF EVIDENCE: Level III, retrospective comparative
      study using prospective data.

PMID- 21168302
TI  - Alcohol consumption in relation to aberrant DNA methylation in breast tumors.
AB  - The mechanism for the observed association of alcohol consumption breast cancer
      risk is not known; understanding that mechanism could improve understanding of
      breast carcinogenesis and optimize prevention strategies. Alcohol may impact
      breast malignancies or tumor progression by altering DNA methylation. We examined
      promoter methylation of three genes, the E-cadherin, p16, and retinoic acid
      binding receptor-beta2 (RAR-beta2) genes in archived breast tumor tissues from
      participants in a population-based case-control study. Real time methylation
      specific PCR was performed on 803 paraffin-embedded samples, and lifetime alcohol
      consumption was queried. Unordered polytomous and unconditional logistic
      regression were used to derive adjusted odds ratios (ORs) and 95% confidence
      intervals (CIs). RAR-beta2 methylation was not associated with drinking. Among
      premenopausal women, alcohol consumption was also not associated with promoter
      methylation for E-cadherin and p16 genes. In case-case comparisons of
      postmenopausal breast cancer, compared with lifetime never drinkers, promoter
      methylation likelihood was increased for higher alcohol intake for E-cadherin
      (OR=2.39; 95% CI, 1.15-4.96), in particular for those with estrogen receptor
      negative tumors (OR=4.13; 95% CI, 1.16-14.72), and decreased for p16 (OR=0.52;
      95% CI, 0.29-0.92). There were indications that the association with p16 was
      stronger for drinking at younger ages. Methylation was also associated with
      drinking intensity independent of total consumption for both genes. We found
      alcohol consumption was associated with DNA methylation in postmenopausal breast
      tumors, suggesting that the association of alcohol and breast cancer may be
      related, at least in part, to altered methylation, and may differ by drinking
      pattern.

PMID- 21168304
TI  - Dislocated polyethylene inserts in fixed-bearing total knee arthroplasty.
AB  - Three cases of a dislocated polyethylene insert in a fixed-bearing total knee
      arthroplasty are presented. This brief report demonstrates the presentation of
      this rare mode of failure and highlights the unique complications associated with
      its treatment.

PMID- 21168306
TI  - Left ventricular mechanics in asymptomatic normotensive and hypertensive patients
      with aortic regurgitation.
AB  - BACKGROUND: The aims of this study were to detect subclinical left ventricular
      (LV) dysfunction and to determine the impact of arterial hypertension on LV
      systolic function using speckle-tracking echocardiography in patients with
      chronic aortic regurgitation (AR). METHODS: Sixty-eight patients with AR and 47
      healthy controls were included in the study. LV rotation and longitudinal,
      radial, and circumferential strain were measured using speckle-tracking imaging.
      RESULTS: Longitudinal axis dysfunction was found in patients with moderate AR
      with hypertension but was not present in patients with moderate AR without
      hypertension. Radial strain in patients with moderate AR was unchanged, but
      reduced levels were noted at the apical level in patients with severe AR without
      hypertension and preserved in those with severe hypertensive AR. LV basal
      rotation was reduced in patients with severe AR, whereas apical rotation was
      increased in those with moderate AR. LV torsion was reduced in patients with
      severe AR. CONCLUSIONS: Patients with asymptomatic AR show subclinical LV
      longitudinal axis dysfunction, with more attenuation demonstrated in hypertensive
      than in normotensive patients.

PMID- 21168307
TI  - Short-term blueberry-enriched diet prevents and reverses object recognition
      memory loss in aging rats.
AB  - OBJECTIVE: Previously, 4 mo of a blueberry-enriched (BB) antioxidant diet
      prevented impaired object recognition memory in aging rats. Experiment 1
      determined whether 1- and 2-mo BB diets would have a similar effect and whether
      the benefits would disappear promptly after terminating the diets. Experiment 2
      determined whether a 1-mo BB diet could subsequently reverse existing object
      memory impairment in aging rats. METHODS: In experiment 1, Fischer-344 rats were
      maintained on an appropriate control diet or on 1 or 2 mo of the BB diet before
      testing object memory at 19 mo postnatally. In experiment 2, rats were tested for
      object recognition memory at 19 mo and again at 20 mo after 1 mo of maintenance
      on a 2% BB or control diet. RESULTS: In experiment 1, the control group performed
      no better than chance, whereas the 1- and 2-mo BB diet groups performed similarly
      and significantly better than controls. The 2-mo BB-diet group, but not the 1-mo
      group, maintained its performance over a subsequent month on a standard
      laboratory diet. In experiment 2, the 19-mo-old rats performed near chance. At 20
      mo of age, the rats subsequently maintained on the BB diet significantly
      increased their object memory scores, whereas the control diet group exhibited a
      non-significant decline. The change in object memory scores differed
      significantly between the two diet groups. CONCLUSION: These results suggest that
      a considerable degree of age-related object memory decline can be prevented and
      reversed by brief maintenance on BB diets.

PMID- 21168305
TI  - Chemical synaptic and gap junctional interactions between principal neurons:
      partners in epileptogenesis.
AB  - Field potential signals, corresponding to electrographic seizures in cortical
      structures, often contain two components, which sometimes appear to be separable
      and other times to be superimposed. The first component consists of low-amplitude
      very fast oscillations (VFO, >70-80 Hz); the second component consists of larger
      amplitude transients, lasting tens to hundreds of ms, and variously called
      population spikes, EEG spikes, or bursts--terms chosen in part because of the
      cellular correlates of the field events. To first approximation, the two
      components arise because of distinctive types of cellular interactions: gap
      junctions for VFO (a model of which is reviewed in the following), and recurrent
      synaptic excitation and/or inhibition for the transients. With in vitro studies
      of epileptic human neocortical tissue, it is possible to elicit VFO alone, or VFO
      superimposed on a large transient, but not a large transient without the VFO. If
      such observations prove to be general, they would imply that gap junction
      mediated interactions are the primary factor in epileptogenesis. It appears to be
      the case then, that in the setting of seizure initiation (but not necessarily
      under physiological conditions), the gain of gap junction-mediated circuits can
      actually be larger than the gain in excitatory synaptic circuits.

PMID- 21168308
TI  - Body composition of Cameroonian lactating women determined by anthropometry,
      bioelectrical impedance, and deuterium dilution.
AB  - OBJECTIVE: This study compared body composition estimates using deuterium
      dilution, multiple-frequency bioelectrical impedance analysis (BIA), and skinfold
      thickness techniques in a group of Cameroonian lactating women. METHODS: Body
      fat, fat-free mass, and total body water in 44 Cameroonian lactating women (2.63
      +/- 1.31 mo postpartum) were assessed by deuterium dilution, the Siri or black
      specific derived Durnin-Womerley equation, and 12 BIA-prediction equations
      developed in samples of subjects of white, black, black-and-white, or unspecified
      racial background, respectively. RESULTS: Compared with deuterium dilution,
      anthropometry and BIA-based predictive equations overestimated body fat by 2.7 to
      11.7 kg; thus, fat-free mass and total body water were underestimated. In all
      cases, the significant biases resulted in large 95% limits of agreement, yielding
      unacceptable potential bias at the level of the individual. However, the
      exclusion of suprailiac skinfold in the calculation, yielding to non-significant
      (P < 0.05) bias, improved the prediction of body composition in Cameroonian
      lactating women using the Durnin-Womersley and Siri equations. CONCLUSION: It is
      essential to adjust the Durnin-Womersley equation before using it in the Siri
      equation for the prediction of body composition in lactating women. Further
      development and cross-validation of prediction equations from BIA specific to
      lactating women is needed.

PMID- 21168309
TI  - Is peripheral alcohol injection of value in the treatment of trigeminal
      neuralgia? An analysis of 100 cases.
AB  - This retrospective study assessed the effectiveness and complications of
      peripheral alcohol injections in the management of trigeminal neuralgia (TN). 100
      patients were analyzed who received 250 peripheral alcohol injections from June
      2004 to January 2010. The duration of effect of alcohol blocks, the effect of
      repeated administration, and complications associated with alcohol injections
      were examined. The distal injection technique was applied. The branch of the
      nerve was identified and confirmed. After carefully anesthetizing the nerve with
      local anesthesia, 1-1.5 ml of absolute alcohol was injected depending on the
      nerve involved. Pain relief lasted for a mean of 14.13 +/- 8.66 months. There was
      a fall in the duration of effect with subsequent injections. No serious
      complications were reported. Only 3% patients presented with non-neuralgic pain,
      swelling, burning sensation, trismus, dysesthesia, soreness, infection and the
      expected loss of sensation along the branch involved in TN. The combination of
      efficacy and reduced morbidity makes this procedure preferable for the treatment
      of TN. Alcohol injections are useful in those who are refractory to drug therapy,
      the elderly, medically compromised patients, unwilling to undergo neurosurgical
      procedures and in whom surgery is delayed for any reason.

PMID- 21168310
TI  - Impact of CYP2C19 polymorphism on residual platelet reactivity in patients with
      coronary heart disease during antiplatelet therapy.
AB  - BACKGROUND AND PURPOSE: CYP2C19*2 loss-of-function allele in Caucasians may be
      associated with wide interindividual variability in platelet response to
      clopidogrel, and the incidence of gene mutation varies with racial differences,
      especially between Asians and Caucasians. The aim was to examine the impact of
      CYP2C19 genotype on the residual platelet reactivity in Japanese patients with
      coronary heart disease (CHD) during antiplatelet therapy. METHODS AND RESULTS: We
      measured the CYP2C19 genotype and platelet aggregation in 201 patients with
      stable CHD. Moreover, we examined the relation of CYP2C19 polymorphism to
      cardiovascular events in 98 patients treated with stent implantation. The
      distribution of CYP2C19 genotype was 37%, 33%, 11%, 11%, 7%, and 1% in
      CYP2C19*1/*1, *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3, respectively. Residual
      platelet reactivity was lower in patients during dual antiplatelet therapy (DAT)
      than in those with aspirin (3975 +/- 1569 aggregation units minute (AU min) vs
      5850 +/- 938 AU min, p<0.05). In the DAT group, the platelet reactivity decreased
      significantly in the wild-type homozygotes (CYP2C19*1/*1), subsequently in the
      *2, or *3 heterozygotes (*1/*2, *1/*3), and was not well inhibited in the *2,
      and/or *3 homozygotes (*2/*2, *2/*3, *3/*3; 3194 +/- 1570 AU min, 4148 +/- 1400
      AU min, and 5088 +/- 1080 AU min, respectively). However, when the duration of
      DAT was used to divide subjects into 2 groups, <7 days, and >7 days, patients
      carrying the variant allele showed significantly decreased platelet reactivities
      at >7 days compared with those at <7 days. Moreover, the incidence of
      cardiovascular events was higher in patients carrying at least one variant allele
      than in wild-type homozygotes. CONCLUSIONS: CYP2C19 polymorphism may be
      associated with high residual platelet reactivity and the occurrence of
      cardiovascular events.

PMID- 21168311
TI  - Low atrial septal pacing with dual-chamber pacemakers reduces atrial fibrillation
      in sick sinus syndrome.
AB  - BACKGROUND: Sick sinus syndrome (SSS) is often complicated with the additional
      presence of atrial fibrillation (AF). Atrial septal pacing, compared with right
      atrial appendage (RAA) pacing, shortens the atrial conduction time and reduces
      the dispersion of the refractoriness. However, low atrial septal (LAS) pacing's
      efficacy for preventing AF in SSS remains controversial in Japan. METHODS AND
      RESULTS: We analyzed 95 consecutive patients with SSS who underwent dual-chamber
      pacemaker implantations. Forty-two patients (44%) had a history of AF at the time
      of the pacemaker implantation. In the group without a history of AF, LAS pacing
      was performed in 17 patients, and RAA pacing in 36 patients. In the group with a
      history of AF, LAS pacing was performed in 15 patients, and RAA pacing in 27
      patients. We evaluated whether LAS pacing prevented the development of de novo AF
      and the persistence of AF after pacemaker implantations. No significant
      differences were found in the baseline characteristics between the RAA and LAS
      groups regardless of an AF history. During a 1-year follow-up period, in the SSS
      patients without a history of AF, 19.0% (7/36) of the RAA group developed de novo
      AF, however, 5.9% (1/17) of the LAS group developed de novo AF (p=0.20). On the
      other hand, in the SSS patients with a history of AF, 22.0% (6/27) of the RAA
      group developed persistent AF, but none of the LAS group developed any persistent
      AF (p=0.049). There were no post-operative complications related to the LAS
      pacing. CONCLUSIONS: LAS pacing is safe and feasible. LAS pacing may prevent the
      progression to persistent AF in SSS patients with dual-chamber pacemakers.

PMID- 21168312
TI  - Granzyme B as a novel factor involved in cardiovascular diseases.
AB  - Apoptosis plays an important role in cardiovascular diseases such as
      atherosclerosis, ischemic heart disease, and congestive heart failure. Previous
      studies have demonstrated that oxidative stress, physiological stress, and
      inflammatory cytokines such as tumor necrosis factor and Fas ligand are involved
      in apoptosis of cardiovascular system. We demonstrate that another apoptosis
      related pathway, i.e. granzyme B/perforin system is involved in cardiovascular
      diseases. Expression of granzyme B, a member of serine protease family is
      increased in acute coronary syndrome, coronary artery disease with end-stage
      renal disease, and subacute stage of acute myocardial infarction. Although
      granzyme B is extensively researched in immunological disorders, the role of
      granzyme B/perforin system was not clear in the cardiovascular field. In
      addition, little is known regarding the inhibition of granzyme B system in the
      clinical situation. In this review we demonstrate recent findings of granzyme B
      in cardiovascular diseases and possible therapeutic applications of inhibiting
      the granzyme B/perforin system.

PMID- 21168313
TI  - Dissociation between diffusion MR tractography density and strength in epilepsy
      patients with hippocampal sclerosis.
AB  - Mesial temporal lobe epilepsy (MTLE) is hypothesized to involve derangement of
      long-range limbic connectivity, but in vivo evidence is lacking. We used
      diffusion tractography to investigate the relationship between hippocampal
      atrophy and connectivity in MTLE patients with hippocampal sclerosis (HS).
      Atrophy was correlated with relatively decreased connectivity density but
      increased connectivity strength, suggesting that HS is accompanied by relatively
      sparse but strong connections as measured by diffusion anisotropy.

PMID- 21168314
TI  - Collagen vascular diseases and enhanced radiotherapy-induced normal tissue
      effects--a case report and a review of published studies.
AB  - Collagen vascular diseases (CVD) are a group of chronic, autoimmune conditions
      that can affect multiple organ systems. The mainstay of treatment involves the
      use of immunosuppressants. CVDs and immunosuppression increase the risk of these
      patients developing malignancy. The mechanisms through which these patients
      develop CVDs show similarities to those for radiotherapy late effects, especially
      fibrosis (via transforming growth factor beta). Radiotherapy may in fact cause an
      active state to develop from a quiescent state of CVD, or exacerbate a pre
      existing CVD. CVDs are said to be associated with increased normal tissue
      toxicity after radiotherapy. Here we present a case report of a patient with a
      long history of systemic lupus erythematosus and oropharyngeal carcinoma, treated
      with synchronous chemoradiotherapy. We also review published studies and
      formulate some guidance on the radiotherapy management of these patients.

PMID- 21168315
TI  - Relationship of adiposity and body composition to the status of metabolic
      syndrome among ethnic Chinese Taiwanese.
AB  - BACKGROUND AND AIMS: The predictive power of adiposity and body compositions
      measured from bioelectrical impedance analysis (BIA) for identifying the risk of
      metabolic syndrome is unknown among ethnic Chinese. METHODS AND RESULTS: We
      designed a nested case-control study by recruiting 1000 cases of metabolic
      syndrome and 986 matched controls from a health checkup center. For identifying
      the metabolic syndrome status, the highest areas under receiver operating
      characteristic curve (AUCs) were waist-height ratio (WHtR) (0.967, 95% confidence
      interval [CI], 0.960-0.976). The body fat mass vs. lean body mass and body mass
      index (BMI) had a similar AUC (0.896 for fat mass vs. lean body mass, 0886 for
      BMI, P=0.07). WHtR and waist circumference had the highest correctly classified
      proportions (0.89-0.90) and the highest Youden's index (0.77-0.81). The optimal
      cut point for WHtR was 52.5, with a sensitivity of 0.92 and specificity of 0.89
      for discriminating metabolic syndrome risk. The incremental values of AUC, net
      reclassification improvement and integrated discrimination improvement values
      were still highest among WHtR, waist circumference and the percent body fat in
      the multivariate logistic model. CONCLUSION: Waist circumference and BIA-derived
      body component measures are suitable for clinical application in identifying the
      metabolic syndrome status among ethnic Chinese in Taiwan.

PMID- 21168316
TI  - Aquaporin 1 water channel is expressed on submucosal but not myenteric neurons
      from the ovine duodenum.
AB  - Aquaporins are a large family of small integral membrane proteins that function
      as molecular water channels. Increasing evidence indicates that an aquaporin 1
      (AQP1) water channel is present on the surface of discrete neuronal classes of
      the central as well peripheral nervous systems. The aim of the present study has
      been to immunohistochemically localize AQP1 in the enteric nervous system (ENS)
      of the sheep duodenum. Specific antibodies to vasoactive intestinal polypeptide
      (VIP) and substance P (SP) were also used to biochemically determine possible
      function(s) of AQP1-positive enteric neurons. The expression of AQP1 in neuronal
      cell cultures has been also studied. Under normal conditions, approximately 30%
      of submucosal neurons exhibit the presence of AQP1 water channels. Neither
      myenteric neurons nor enteric nerve fibres showed immunoreactivity to AQP1. The
      vast majority of AQP1-bearing submucosal neurons were immunoreactive (IR) to SP
      (but not to VIP). Moderate numbers of SP-IR as well as VIP-IR nerve fibres run in
      close vicinity to AQP1-positive small blood/lymphatic vessels. SP-positive as
      well as VIP-positive nerve fibres were regularly observed to be in close contact
      with AQP1-positive submucosal neurons. After 3, 6 and 9 days of in vitro
      culturing, respectively, myenteric neurons still exhibited no presence of AQP1
      channels. The obtained results indicated that in ENS of the ovine duodenum the
      expression of AQP1 is species-related and predominantly seen in a significant
      subpopulation of probably sensory submucosal neurons. Since we show no
      upregulation of AQP1 channels in cultured myenteric neurons we suggest that AQP1
      is not a significant factor involved in environmental adaptation of myenteric
      neurons to the artificial conditions.

PMID- 21168317
TI  - Effect of the dietary oregano (Origanum vulgare) on Cu and Zn balance in weaned
      piglets.
AB  - A 4-week study conducted on 20 weaned piglets (average initial weight 15 kg)
      evaluated the effects of dietary oregano (Origanum vulgare) used in the
      presence/absence of phytase on the Cu and Zn balance, while reducing/eliminating
      their inclusion in the diet as inorganic salts. Oregano was harvested from the
      wild flora. The Cu and Zn concentrations that were taken into consideration (9.85
      ppm and 53.31 pmm, respectively) were the consensus values obtained in an
      interlaboratory study. The piglets were assigned to 4 groups (C, E1, E2, E3),
      housed in individual metabolic cages and fed on corn-soybean meal-based diets.
      The diet of the control group (C) with addition of 1% inorganic mineral premix
      (MP), contained: 40.92 ppm Cu, 144.96 ppm Zn. The experimental diets differed
      from the C diet as follows: E1--3% oregano, 0% phytase (5000 PU/g), 0% MP; E2--3%
      oregano, 0.01% phytase, 0% MP; E3--3% oregano, 0% phytase, 0.5% MP, E4--3%
      oregano, 0.01% phytase, 0,5% premix. For groups E1, E2, E3 and E4, 0.5% Zn of the
      MP were included in the diet, because the dietary oregano amount did not meet the
      requirements (NRC) for piglets. The mineral balance was determined during 3
      periods of 5 days each. The levels of Cu and Zn were measured by FAAS in the
      samples (weekly samples/piglet) of ingesta, faeces and urine. It was noticed that
      although the dietary Cu ingested by the groups without MP was 75% (10.08 ppm)
      lower than C, the absorption coefficients were only 47% (28.83) lower than for
      group C (54.22%), while in the groups with 0.5% MP, the absorption was just 10%
      (48.86%) lower than for group C. For Zn, where the amount ingested by the
      experimental groups was 33% (97.62 ppm) lower than for group C, the absorption
      coefficients were just 20% (46.3%) lower than for group C (57.64%). No
      significant differences were noticed for Cu and Zn in terms of apparent
      absorption, between the groups with/without phytase. The deposits of Cu and Zn in
      the main organs and serum (from slaughtered piglets) were also evaluated.

PMID- 21168318
TI  - Self-antigen presentation by dendritic cells and lymphoid stroma and its
      implications for autoimmunity.
AB  - The induction and maintenance of T cell tolerance is essential to prevent
      autoimmunity. A combination of central and peripheral mechanisms acts to control
      autoreactive T cells. In secondary lymphoid organs, dendritic cells (DCs)
      presenting self-antigen were thought to play a major role in the induction of
      peripheral T cell tolerance. Multiple recent studies have demonstrated that DCs
      are not absolutely essential to induce and maintain tolerance. Furthermore, it
      has also been recently shown that non-hematopoietic stromal cells expressing
      peripheral tissue-restricted antigens can induce T cell tolerance, independently
      of DCs. Together these studies imply that peripheral tolerance is more complex
      than previously thought and a consequence of the tolerogenic functions of the
      hematopoietic and non-hematopoietic compartments within secondary lymphoid
      organs.

PMID- 21168320
TI  - WITHDRAWN: An electrochemical L -Cysteine biosensor based on Iron (III) oxide
      core-cobalt hexacyanoferrate shell nanoparticles-carbon microparticles
      nanocomposite.
AB  - This article has been withdrawn at the request of the 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- 21168321
TI  - From the model to the crop: genes controlling tuber formation in potato.
AB  - Photoperiod regulates many different developmental processes, including floral
      induction in several species and tuber formation in potato. Research in
      Arabidopsis led to the identification of FLOWERING LOCUS T (FT) as a main
      component of the florigen or mobile flowering promoting signal produced in the
      leaves. A similar mobile signal or tuberigen has been reported to induce tuber
      formation in potato, recent evidence obtained in our laboratory indicates that a
      potato homolog of FT encodes this signal. Flowering regulators, like CONSTANS and
      miR172, also play a role in tuberization, although it remains unclear whether
      these regulators function in identical pathways. Here, we highlight differential
      regulation of these genes in flowering and tuberization control and discuss on
      their possible tuberization-related function.

PMID- 21168319
TI  - The binary switch that controls the life and death decisions of ER stressed beta
      cells.
AB  - Diabetes mellitus is a group of common metabolic disorders defined by
      hyperglycemia. One of the most important factors contributing to hyperglycemia is
      dysfunction and death of beta cells. Increasing experimental, clinical, and
      genetic evidence indicates that endoplasmic reticulum (ER) stress plays an
      important role in beta cell dysfunction and death during the progression of type
      1 and type 2 diabetes as well as genetic forms of diabetes such as Wolfram
      syndrome. The mechanisms of ER stress-mediated beta cell dysfunction and death
      are complex and not homogenous. Here we review the recent key findings on the
      role of ER stress and the unfolded protein response (UPR) in beta cells and the
      mechanisms of ER stress-mediated beta cell dysfunction and death. Complete
      understanding of these mechanisms will lead to novel therapeutic modalities for
      diabetes.

PMID- 21168322
TI  - Applications of computational science for understanding enzymatic deconstruction
      of cellulose.
AB  - Understanding the molecular-level mechanisms that enzymes employ to deconstruct
      plant cell walls is a fundamental scientific challenge with significant
      ramifications for renewable fuel production from biomass. In nature, bacteria and
      fungi use enzyme cocktails that include processive and non-processive cellulases
      and hemicellulases to convert cellulose and hemicellulose to soluble sugars.
      Catalyzed by an accelerated biofuels R&D portfolio, there is now a wealth of new
      structural and experimental insights related to cellulases and the structure of
      plant cell walls. From this background, computational approaches commonly used in
      other fields are now poised to offer insights complementary to experiments
      designed to probe mechanisms of plant cell wall deconstruction. Here we outline
      the current status of computational approaches for a collection of critical
      problems in cellulose deconstruction. We discuss path sampling methods to measure
      rates of elementary steps of enzyme action, coarse-grained modeling for
      understanding macromolecular, cellulosomal complexes, methods to screen for
      enzyme improvements, and studies of cellulose at the molecular level. Overall,
      simulation is a complementary tool to understand carbohydrate-active enzymes and
      plant cell walls, which will enable industrial processes for the production of
      advanced, renewable fuels.

PMID- 21168323
TI  - Bacterial SOS response: a food safety perspective.
AB  - The SOS response is a conserved inducible pathway in bacteria that is involved in
      DNA repair and restart of stalled replication forks. Activation of the SOS
      response can result in stress resistance and mutagenesis. In food processing
      facilities and during food preservation, bacteria are exposed to stresses and
      stimuli that potentially activate the SOS response, resulting in resistant or
      adapted bacteria. This review places the bacterial SOS response in a food safety
      perspective by providing an overview of the known triggers of the SOS response
      mechanism and its impact on the survival of spoilage and pathogenic bacteria.

PMID- 21168324
TI  - A stress-free walk from Arabidopsis to crops.
AB  - Global concerns such as food security and climate change have highlighted an
      urgent need for improved crop yield. Breakthroughs in Arabidopsis research
      provide fresh application routes to achieve novel crop varieties that can
      withstand or avoid stresses imposed by a changing growth environment. This review
      features advances in CBF-stress signalling that expand opportunities to produce
      super hardy crops that can withstand multiple abiotic stresses. It examines
      molecular external coincidence mechanisms that avoid abiotic stresses by
      confining plant growth and reproduction to favourable times of the year. The
      potential value of mathematical modelling approaches is discussed in relation to
      improving crop-stress resistance or avoidance, and forecasting crop performance.

PMID- 21168325
TI  - Multiple complications following the use of prophylactic internal iliac artery
      balloon catheterisation in a patient with placenta percreta.
AB  - The incidence of placenta praevia/accreta is increasing, placing women at
      significant risk of postpartum haemorrhage with associated morbidity and
      mortality. National guidelines recommend prophylactic placement of internal iliac
      artery balloon occlusion catheters for women with abnormal placentation. We
      describe an elective caesarean delivery in a patient with placenta percreta who
      underwent this technique. She developed bilateral pseudoaneurysms, unilateral
      arterial rupture and compromised vascular supply to her right leg secondary to
      thrombus formation, and suffered massive haemorrhage, both despite and as a
      result of intervention. This is the first case report of multiple complications
      in an obstetric patient after temporary internal iliac balloon occlusion in an
      elective setting.

PMID- 21168326
TI  - The use of thromboelastography for the peripartum management of a patient with
      platelet storage pool disorder.
AB  - We describe the peripartum management of a 26-year-old primigravida with a
      platelet storage pool disorder who underwent spontaneous vaginal delivery of
      twins with epidural analgesia. Postpartum hemorrhage from uterine atony, and
      cervical and vaginal lacerations were treated successfully with 1-desamino-8D
      arginine vasopressin and blood products. The use of thromboelastography in the
      assessment and management of bleeding risk in the setting of platelet storage
      pool disorder is described.

PMID- 21168327
TI  - Telomerase structure function.
AB  - Telomeres and their associated proteins are specialized structures at the ends of
      linear chromosomes that function as caps that protect the DNA from exonuclease
      degradation and recombination events that could lead to genomic instability. In
      this review, we discuss recent publications describing the high-resolution
      structures of individual domains and of the full-length catalytic subunit of
      telomerase alone and in complex with its putative RNA template and telomeric DNA.
      These structures, together with existing biochemical data, provide novel insights
      into the basic mechanism of telomere replication and length homeostasis by
      telomerase. Moreover, these data further enrich our understanding of the
      mechanism of DNA replication by polymerases in general and they provide a
      framework to design small molecule inhibitors of telomerase that may be of
      therapeutic value for cancer and other diseases associated with cellular aging.

PMID- 21168328
TI  - Distinction of isolated tumour cells and micrometastasis in lymph nodes of breast
      cancer patients according to the new Tumour Node Metastasis (TNM) definitions.
AB  - Isolated tumour cells and micrometastases represent two different staging
      categories and are often dealt with differently when identified in sentinel lymph
      nodes of breast cancer patients. The reproducibility of these categories was
      found to be suboptimal in several studies. The new edition of the TNM (Tumour
      Node Metastasis) is expected to improve the reproducibility of these categories.
      Fifty cases of possible low-volume nodal involvement were represented by one to
      four digital images and were analysed by members of the European Working Group
      for Breast Screening Pathology (EWGBSP). The kappa value for interobserver
      agreement of the pN (TNM) staging categories and of the isolated tumour cells
      category were 0.55 and 0.56 reflecting moderate reproducibility, and the kappa of
      the micrometastatic category (0.62) reflected substantial reproducibility. This
      is an improvement over the results gained on the basis of the previous edition of
      the TNM. Maximal adherence to the category definitions supplemented by
      explanatory texts in the staging manual should result in more homogeneous nodal
      staging of breast cancer.

PMID- 21168329
TI  - New furin inhibitors based on weakly basic amidinohydrazones.
AB  - A novel series of amidinohydrazone-derived furin inhibitors was prepared; the
      most potent compounds 17 and 21 inhibit furin with K(i) values of 0.46 and
      0.59MUM, respectively. In contrast to inhibitor 17, which still contains a
      guanidino residue, compound 21 possesses only weakly basic amidinohydrazone
      groups.

PMID- 21168330
TI  - In vitro efficacy of 7-benzylamino-1-isoquinolinamines against Plasmodium
      falciparum related to the efficacy of chalcones.
AB  - A series of 1,7-diaminoisoquinolinamines, that are expected to mediate
      antimalarial activity by the same mechanism employed by the chalcones, were
      produced. Six 7-benzylamino-1-isoquinolinamines were found to be submicromolar
      inhibitors in vitro of drug-resistant Plasmodium falciparum, with the best
      possessing activity comparable to chloroquine. Despite being developed from a
      lead that is a DHFR inhibitor, these compounds do not mediate their antimalarial
      effects by inhibition of DHFR.

PMID- 21168331
TI  - The effect of 5-substitution on the electrochemical behavior and antitubercular
      activity of PA-824.
AB  - Nitroimidazole PA-824 is part of an exciting new class of compounds currently
      undergoing clinical evaluation as novel TB therapeutics. The recently elucidated
      mechanism of action of PA-824 involves reduction of the nitroimidazole ring and
      subsequent nitric oxide release. The importance of this compound and its unique
      activity prompted us to explore how substitution of the nitroimidazole ring would
      affect electrochemical reduction and antitubercular activity. We prepared analogs
      of PA-824 with bromo, chloro, cyano, and amino substituents in the 5-position of
      the aromatic ring. We found that substitution of the imidazole ring greatly
      influences reduction and the stability of the corresponding nitro radical anion.
      Further, the antitubercular activities of the bromo and chloro analogs may
      indicate that an alternate nitroreductase pathway within Mycobacterium
      tuberculosis exists.

PMID- 21168332
TI  - (13)C-labeled indolequinone-DTPA-Gd conjugate for NMR probing cytochrome:P450
      reductase-mediated one-electron reduction.
AB  - We designed and synthesized a new class of (13)C-labeled NMR probe, (13)C-IQ-Gd,
      to monitor one-electron reductions by cytochrome:P450 (CYP450) reductase under
      hypoxic conditions. (13)C-IQ-Gd consisted of a Gd(3+)-diethylene triamine
      pentaacetic acid (DTPA) complex unit and an indolequinone ((13)C-IQ) unit bearing
      a (13)C-labeled methoxy group. The (13)C NMR signal of (13)C-IQ-Gd was suppressed
      because of the intramolecular paramagnetic effect of Gd(3+), whereas enzymatic
      reduction mediated by CYP450 reductase under hypoxic conditions yielded an
      intensed (13)C NMR signal due to enzymatic activation of the IQ unit followed by
      release of the DTPA-Gd unit from (13)C-IQ-Gd. This (13)C NMR spectral change
      allowed the monitoring of CYP450 reducatase-mediated one-electron reduction.

PMID- 21168333
TI  - Structure of rat aldose reductase-like protein AKR1B14 holoenzyme: Probing the
      role of His269 in coenzyme binding by site-directed mutagenesis.
AB  - Rat aldose reductase-like protein (AKR1B14) is the ortholog of mouse vas deferens
      protein (AKR1B7) playing roles in detoxification of reactive aldehydes and
      synthesis of prostaglandin F(2alpha). The crystal structure of the binary complex
      (AKR1B14-NADPH) was determined at 1.86A resolution, and showed that the adenine
      ring and the 2'-phosphate group of the coenzyme formed pi-stacking and
      electrostatic interactions with the imidazole ring and ND1 atom, respectively, of
      His269, which is not conserved in other aldose reductase-like proteins. The
      interactions were supported by site-directed mutagenesis of His269 to Arg, Phe
      and Met, which increased the K(m) for NADPH by 4, 7 and 127-fold, respectively.
      This is the first report of the tertiary structure of a rodent AKR1B7 ortholog,
      which describes the role of a novel dual interaction for the non-conserved His269
      in coenzyme binding.

PMID- 21168334
TI  - Muscle strength and kinetic gait pattern in children with bilateral spastic CP.
AB  - Cerebral palsy is often associated with an abnormal gait pattern. This study put
      focus on relation between muscle strength and kinetic gait pattern in children
      with bilateral spastic cerebral palsy and compares them with a reference group.
      In total 20 children with CP and 20 typically developing children participated.
      They were all assessed with measurement of muscle strength in eight muscle groups
      in the legs and a 3-dimensional gait analysis including force data. It was found
      that children with CP were not only significantly weaker in all muscle groups but
      also walked with slower velocity and shorter stride length when compared with the
      reference group. Gait moments differed at the ankle level with significantly
      lower moments in children with CP. Gait moments were closer to the maximal muscle
      strength in the group of children with CP. Furthermore a correlation between
      plantarflexing gait moment and muscle strength was observed in six of the eight
      muscle groups in children with CP, a relation not found in the reference group. A
      similar pattern was seen between muscle strength and generating ankle power with
      a rho=0.582-0.766. The results of this study state the importance of the
      relationship of the overall muscle strength pattern in the lower extremity, not
      only the plantarflexors.

PMID- 21168335
TI  - Reduction of vinyl groups in naturally occurring chlorophylls-a.
AB  - 3,8-Divinyl-chlorophyll(Chl)-a possessing a phytyl ester was hydrogenated in
      acetone by rhodium catalyst on alumina to afford 3-vinyl-8-ethyl-, 3-ethyl-8
      vinyl- and 3,8-diethyl-Chls. The ratio of produced 3-ethyl-8-vinyl- over 3-vinyl
      8-ethyl-Chls was determined to be 1.2, indicating that the reactivity of the 3
      vinyl group was slightly higher than that of the 8-vinyl group. Catalytic
      hydrogenation of divinyl-protochlorophyll-a possessing a porphyrin pi-skeleton
      (C17C18) instead of the above chlorin moiety (C17H-C18H) gave an equal amount of
      mono-reduced regioisomers. The slight (or no) selectivity is different from that
      in the enzymatic reduction of divinyl-(proto)chlorophyllides-a lacking a phytyl
      ester in the biosynthetic pathway of Chl-a where the sole 8-vinyl group is
      transformed to the ethyl group.

PMID- 21168337
TI  - Monitoring of MNSR operation by measuring subcritical photoneutron flux.
AB  - Passive nondestructive assay methods are used to monitor the reactor's operation.
      It is required for nuclear regulatory, calculation validation and safeguards
      purposes. So, it plays a vital role in the safety and security of the nuclear
      plants. The possibility of MNSR operation monitoring by measuring the subcritical
      state photoneutron flux were investigated in this work. The photoneutron flux is
      induced by the fuels hard gamma radiation in the beryllium reflector. Theoretical
      formulation and experimental tests were performed. The results show that within a
      specified cooling time range, the photoneutron flux is induced by a single
      dominant hard gamma emitter such as (117)Cd (activation product) and (140)Ba
      ((140)La fission product). This phenomenon was utilized to monitor the cooling
      time and the operation neutron flux during the last campaign. Thus a passive
      nondestructive assay method is proposed with regard to the reactor operation's
      monitoring.

PMID- 21168336
TI  - Virtual screening based identification of novel small-molecule inhibitors
      targeted to the HIV-1 capsid.
AB  - The hydrophobic cavity of the C-terminal domain (CTD) of HIV-1 capsid has been
      recently validated as potential target for antiviral drugs by peptide-based
      inhibitors; however, there is no report yet of any small molecule compounds that
      target this hydrophobic cavity. In order to fill this gap and discover new
      classes of ant-HIV-1 inhibitors, we undertook a docking-based virtual screening
      and subsequent analog search, and medicinal chemistry approaches to identify
      small molecule inhibitors against this target. This article reports for the first
      time, to the best of our knowledge, identification of diverse classes of
      inhibitors that efficiently inhibited the formation of mature-like viral
      particles verified under electron microscope (EM) and showed potential as anti
      HIV-1 agents in a viral infectivity assay against a wide range of laboratory
      adapted as well as primary isolates in MT-2 cells and PBMC. In addition, the
      virions produced after the HIV-1 infected cells were treated with two of the most
      active compounds showed drastically reduced infectivity confirming the potential
      of these compounds as anti-HIV-1 agents. We have derived a comprehensive SAR from
      the antiviral data. The SAR analyses will be useful in further optimizing the
      leads to potential anti-HIV-1 agents.

PMID- 21168338
TI  - Physiological responses to salinity in the yellow-horned poppy, Glaucium flavum.
AB  - Glaucium flavum Crantz. is a short-lived perennial herb found in coastal habitats
      in southern Spain growing under a wide range of interstitial soil salinity
      levels, from that of fresh water up to the high concentration typical of sea
      water. An experiment was designed to investigate the effect of exposure to this
      range of salinity on the photosynthetic apparatus, growth and reproduction of G.
      flavum, by measuring relative growth rate, percentage of dead leaves, seed
      production, leaf relative water content, chlorophyll fluorescence parameters, gas
      exchange and photosynthetic pigment concentrations. We also determined total
      sodium, potassium, calcium, magnesium, and nitrogen concentrations. G. flavum
      survived at NaCl concentrations as high as 300 mM, although the excess of NaCl
      resulted in a biomass reduction of between 26 and 76% (in 60 and 300 mM NaCl
      treatments, respectively). The long-term effects of salinity on the growth and
      reproduction of G. flavum were mainly linked to an overall reduction in carbon
      gain as a result of stomatal conductance regulation. Also, the excess of salt
      caused a reduction in pigment concentrations, as well as Ca-, Mg- and N-uptake.
      The results indicate that, in the presence of excess soil-water salinity, G.
      flavum sustains little overall effects on the photochemical (PSII) apparatus, and
      is capable of tolerating a very high and continued exposure to salinity by
      maintaining low levels of net photosynthesis.

PMID- 21168339
TI  - Increased systemic perfusion pressure during cardiopulmonary bypass is associated
      with less early postoperative cognitive dysfunction and delirium.
AB  - OBJECTIVE: Patients undergoing cardiac surgery procedures are thought to be at
      risk of early neuropsychological deficits and delirium. Regional cerebral
      hypoperfusion may play a role in the etiology of this complication. We
      hypothesized that low systemic perfusion pressure during cardiopulmonary bypass
      (CPB) would correlate with early postoperative cognitive dysfunction in on-pump
      patients. METHODS: In this prospective, randomized, single-center trial, we
      assigned 92 patients scheduled for elective or urgent coronary artery bypass
      grafting (CABG) to high-pressure (HP: 80-90 mm Hg, n = 44) or low-pressure (LP:
      60-70 mm Hg, n = 48) perfusion groups during CPB. Patients with prior
      cerebrovascular or psychiatric disorders were excluded. Primary end point was the
      cognitive outcome as measured by Mini-Mental-Status examination before and 48 h
      after surgery. RESULTS: Patients' pre- and intra-operative characteristics did
      not differ between groups. Significantly more patients in the LP group developed
      postoperative delirium than in the HP group (LP 13%. vs HP 0%, p = 0.017). The
      postoperative drop in Mini-Mental-Status scores was significantly greater in the
      LP group (LP 3.9 +/- 6.5 vs HP 1.1 +/- 1.9; p = 0.012). No group differences were
      detected in cerebral oxygenation measured by near-infrared spectroscopy during
      CPB. The LP group's postoperative arterial lactate concentration in the intensive
      care unit was significantly higher as compared with the HP group (LP 2.0 +/- 1.1
      mmol l(-1) vs HP 1.4 +/- 0.6 mmol l(-1); p < 0.001). We observed no differences
      between the groups in any other postoperative clinical, functional, or laboratory
      parameters. CONCLUSION: Maintaining perfusion pressure at physiologic levels
      during normothermic CPB (80-90 mm Hg) is associated with less early postoperative
      cognitive dysfunction and delirium. This perfusion strategy neither increases
      morbidity, nor does it impair organ function.

PMID- 21168340
TI  - Long-term survival and quality of life after cardiac resuscitation following
      coronary artery bypass grafting.
AB  - OBJECTIVE: Follow-up studies of patients surviving emergency resternotomy, open
      cardiac massage, and additional emergency cardiac surgery following coronary
      artery bypass grafting (CABG) remain sparse and studies focusing on health
      related quality of life are lacking. Our aim was to elucidate the long-term
      course of patients experiencing this hazardous complication. METHODS: Between
      1988 and 1999, 76 patients suffered sudden hemodynamic collapse following
      isolated CABG. All patients underwent emergency resternotomy and open cardiac
      massage. An emergency cardiac reoperation was performed in the 62 (82%) primary
      survivors. Additional 76 patients were pair-matched to the study patients on the
      basis of their preoperative characteristics and served as controls. Of the study
      patients, 41 (54%), and of the controls, 76, (100%) were discharged. In December
      2009, all patients were traced with respect to mortality data and the health
      related quality of life of living patients was studied using the RAND-36 Item
      Health Survey questionnaire. RESULTS: Altogether 19 (73%) of the 26 study
      patients, and 38 (84%) of the 45 controls were available. After exclusion of the
      early deaths, the life expectancy was similar between the groups: neither overall
      (p = 0.60) nor cardiac (p = 0.64) survival differed significantly after a mean
      follow-up time of 15.1 +/- 3.5 years. In addition, cardiac re-interventions were
      equally frequently required in both the groups. The RAND-36 scores were congruent
      (p = ns) between the groups and the age- and sex-matched national reference
      population in the health-related quality-of-life dimensions describing physical,
      mental, and social domains. CONCLUSIONS: Patients who have survived severe
      hemodynamic collapse, open cardiac massage, and emergency cardiac reoperation
      following CABG achieve similar long-term prognosis in terms of survival and
      cardiac interventions as the pair-matched control patients. In addition, 15 years
      postoperatively, they have a good health-related quality of life, similar to that
      of an age- and sex-matched national reference population.

PMID- 21168341
TI  - Task-independent metrics to assess the data quality of medical registries using
      the European Society of Thoracic Surgeons (ESTS) Database.
AB  - OBJECTIVE: The quality of data collected into a database is of paramount
      importance in every analysis. No standardized methods are available to quantify
      the quality of data in medical registries. Expanding the work done in other
      fields, we aimed at developing a methodological approach to measure the quality
      of a thoracic surgical database, by using the European Society of Thoracic
      Surgeons (ESTS) Database. METHODS: A selection of anonymized data collected in
      the ESTS Database from 2007 to 2009 was tested using appropriate data quality
      metrics: completeness, correctness, consistency and believability. Particularly,
      the believability value is obtained as a result of a min-max operation based on
      the evaluation of completeness, correctness and consistency. Completeness
      measures the number of missing values in each checked column of the database, and
      it is calculated as number of variables registered/number of variables expected.
      Correctness reflects the number of data units in error referring to a set of
      clearly defined criteria (number of correct data/number of all data counted) and
      consistency is calculated by verifying the number of data in conflict in the same
      recorded patient (number of consistent checks/total number of checks). The
      threshold selected to indicate good quality was 0.8. RESULTS: A total of 49363
      values were reviewed to obtain the quality indicators. The results of the data
      quality assessment for the analyzed section of the ESTS Database are all above
      the predefined threshold: completeness is 0.85, correctness 0.99 and consistency
      0.98. The believability score of data in the database is 0.85. CONCLUSIONS: We
      were able to apply task-independent metrics to measure the quality within the
      ESTS Database. This study may represent a template to be applied in the
      medical/surgical field to test the quality of data in clinical registries. Only
      registries with a high quality of data can be reliably used for scientific,
      managerial and credentialing purposes.

PMID- 21168342
TI  - Pharmacological versus non-pharmacological antipyretic treatments in febrile
      critically ill adult patients: a systematic review and meta-analysis.
AB  - OBJECTIVES: Fever is common in critically ill patients and there are myriad of
      antipyretic and cooling treatments used. A systematic review was undertaken of
      the safety and efficacy of methods used to reduce fever. METHODS: Medline,
      EMBASE, CINAHL and Cochrane Database of Systematic Reviews were searched for
      randomised control trials (RCTs) of head-to-head and versus placebo/no treatment
      comparisons of pharmacological and/or non-pharmacological treatments for reducing
      fever in critically ill adult patients. Primary outcomes were reduction of fever
      and haemodynamic effects of treatments. RESULTS: 11 of 48 trials reviewed were
      included. The studies analysed were separated into common antipyretic treatment
      groups for comparison. Our main findings include, newer versus conventional
      external cooling therapies where newer external cooling methods (intravascular
      cooling and hydrogel cooling system) were better at reducing the fever burden
      than conventional methods (surface cooling) (MD, -8.00, 95% CI=-12.54, -3.47,
      P<0.001), with a trend for higher mortality for newer methods (RR, 1.42; 95% CI,
      0.99-2.03; P=0.06). In the group comparison of the effectiveness of
      pharmacological antipyretic treatments, reduction on core body temperature
      favoured continuous antipyretic infusions rather than bolus doses (MD, 0.30, 95%
      CI 0.09, 0.51, P=0.005). For aggressive versus permissive antipyretic treatments,
      a reduction in mean daily temperatures favoured the aggressive group (MD, -1.09,
      95% CI -1.37, -0.81, P<0.001) with a trend towards higher mortality for
      aggressive treatment (RR, 6.05, 95% CI 0.78, 46.95, P=0.09). CONCLUSION:
      Additional studies are needed to explore and clarify the role of antipyretic
      treatments in febrile critically ill adult patients.

PMID- 21168343
TI  - Mantle cell lymphoma: the promise of new treatment options.
AB  - Though the expected overall survival (OS) for mantle cell lymphoma (MCL) has
      doubled in the last 30 years it is still in the range of only 4-5 years. Despite
      high response rates with current first-line treatments, most patients eventually
      relapse and become typically chemoresistant, leading to very poor outcome in the
      relapsed setting. Here, we summarize the clinical characteristics of MCL and
      frontline strategies used in MCL, and review a number of novel options that are
      currently being investigated in an effort to extend survival outcomes for this
      difficult-to-treat patient population. Among these novel options figure
      cytotoxics (bendamustine, cladribine), new biologicals/small molecules such as
      proteasome inhibitors (bortezomib 1st drug approved in the USA for MCL), mTOR
      inhibitors with temsirolimus (1st drug approved in EU for MCL), CDK inhibitors
      (flavopiridol); IMiDs (thalidomide, lenalidomide); HDAC inhibitors, Bcl-2
      inhibitors and second or third generation monoclonal antibodies or immunotoxins.
      The panel of novel drugs approved or being tested offers new opportunities in the
      management of MCL from combination in the frontline setting (e.g. bortezomib-R
      chemo) to post-induction strategies such as consolidation (e.g.
      radioimmunotherapy, bortezomib) or maintenance therapy (e.g. rituximab,
      lenalidomide).

PMID- 21168344
TI  - Changes in hormone therapy prescriptions among middle-aged women in Taiwan:
      implications for health needs at menopause.
AB  - BACKGROUND: From the 1990s until 2002, hormone therapy (HT) was a popular
      treatment for menopausal syndrome in middle-aged women. Since the Women's Health
      Initiatives (WHI) studies in 2002 warned that the risk of HT might exceed its
      benefits, there has been a reduction in its use worldwide, including in Taiwan.
      Many studies reported this decline, but few discussed whether HT may or may not
      fulfill menopausal women's health needs. This study examines the changes in HT
      prescriptions and other measures by menopausal women in Taiwan and the
      implications of these changes in relation to their needs. METHODS: This study
      analyzes annual and monthly rates of HT prescription and outpatient care
      utilization among Taiwanese women in the 45- to 64-year-old age group. It is
      based on medical claims data of the Taiwan National Health Insurance Programs
      from 2000 to 2004. RESULTS: The data showed that HT was the prevailing treatment
      for menopausal syndrome before the WHI publications. The rate of HT prescription
      increased annually, peaking in 2001 at 21.6%, but declined from 2002 to 9.7% in
      2004. At the same time, the number of Taiwanese women seeking traditional Chinese
      medicine for the menopausal syndrome increased. CONCLUSION: HT prescriptions in
      Taiwan declined significantly after the WHI reports, demonstrating the elasticity
      of the need for HT. But utilization data in Taiwan showed that attendance at
      outpatient clinics at menopause remained constant and the use of traditional
      Chinese medicine increased. Further studies should investigate health needs from
      menopausal women's perspectives to develop appropriate measures to meet their
      needs.

PMID- 21168345
TI  - ABO-incompatible living-donor lobar lung transplantation.
AB  - ABO-incompatible living-donor lobar lung transplantation was performed in a 10
      year-old boy with bronchiolitis obliterans (BO) after bone marrow transplantation
      (BMT) for recurrent acute myeloid leukemia (AML). His blood type had changed from
      AB to O since he underwent BMT and he had no anti-A/B antibody, and received type
      B and AB donor lobar lungs. To our knowledge, this case represents the first
      successful living-donor lobar lung transplantation from ABO-incompatible donors.

PMID- 21168346
TI  - Clinical outcomes for continuous-flow left ventricular assist device patients
      stratified by pre-operative INTERMACS classification.
AB  - BACKGROUND: Risk stratification for mechanical circulatory support (MCS) has
      emerged as an important tool in patient selection and outcomes assessment. Most
      studies examining risk stratification have been limited to pulsatile devices. We
      use the Interagency Registry for Mechanically Assisted Circulatory Support
      (INTERMACS) to stratify patients with continuous-flow devices and assess outcomes
      in less severe, but functionally impaired, heart failure patients. METHODS: This
      study included 101 bridge-to-transplant and destination-therapy patients at 3
      centers. Three groups were studied: Group 1, cardiogenic shock (INTERMACS Profile
      1); Group 2, inotrope-dependent (INTERMACS Profile 2 or 3); and Group 3,
      ambulatory advanced heart failure (INTERMACS Profiles 4 to 7). The outcomes of
      interest were actuarial survival, survival to discharge and length of stay.
      RESULTS: Survival at 36 months was better in Group 3 than in Group 1 (95.8% vs
      51.1%, p = 0.011), but not between Groups 2 and 3 (68.8 vs 95.8%, p = 0.065).
      Lengths of stay for Groups 1 to 3 were 44, 41 and 17 days: Groups 1 vs 3, p <
      0.001; Groups 2 vs 3, p < 0.001; and Groups 1 vs 2, p = 0.62. Lengths of stay for
      survivors were 49, 39 and 14 for the 3 groups: Groups 1 vs 3, p < 0.001; Groups 2
      vs 3, p < 0.001; and Groups 1 vs 2, p = 0.28. CONCLUSION: INTERMACS
      classification is a useful metric for risk-stratifying candidates for MCS. Less
      acutely ill but functionally impaired heart failure patients receiving continuous
      flow LVADs had longer short- and long-term survival and shorter lengths of stay
      compared with patients who were more acutely ill.

PMID- 21168347
TI  - Delayed diagnosis of novel H1N1 influenza pneumonitis in a vaccinated heart
      transplant recipient.

PMID- 21168348
TI  - Characterization of spontaneous recurrent epileptiform discharges in hippocampal
      entorhinal cortical slices prepared from chronic epileptic animals.
AB  - Epilepsy, a common neurological disorder, is characterized by the occurrence of
      spontaneous recurrent epileptiform discharges (SREDs). Acquired epilepsy is
      associated with long-term neuronal plasticity changes in the hippocampus
      resulting in the expression of spontaneous recurrent seizures. The purpose of
      this study is to evaluate and characterize endogenous epileptiform activity in
      hippocampal-entorhinal cortical (HEC) slices from epileptic animals. This study
      employed HEC slices isolated from a large series of control and epileptic animals
      to evaluate and compare the presence, degree and localization of endogenous SREDs
      using extracellular and whole cell current clamp recordings. Animals were made
      epileptic using the pilocarpine model of epilepsy. Extracellular field potentials
      were recorded simultaneously from areas CA1, CA3, dentate gyrus, and entorhinal
      cortex and whole cell current clamp recordings were obtained from CA3 neurons.
      All regions from epileptic HEC slices (n=53) expressed SREDs, with an average
      frequency of 1.3Hz. In contrast, control slices (n=24) did not manifest any
      SREDs. Epileptic HEC slices demonstrated slow and fast firing patterns of SREDs.
      Whole cell current clamp recordings from epileptic HEC slices showed that CA3
      neurons exhibited paroxysmal depolarizing shifts associated with these SREDs. To
      our knowledge this is the first significant demonstration of endogenous SREDs in
      a large series of HEC slices from epileptic animals in comparison to controls.
      Epileptiform discharges were found to propagate around hippocampal circuits. HEC
      slices from epileptic animals that manifest SREDs provide a novel model to study
      in vitro seizure activity in tissue prepared from epileptic animals.

PMID- 21168349
TI  - Microscopic cleanliness evaluation of the apical root canal after using calcium
      hydroxide mixed with chlorhexidine, propylene glycol, or antibiotic paste.
AB  - This study evaluated cleaning of the dentinal wall after removal of different
      calcium hydroxide pastes. Sixty-eight single-rooted teeth were prepared using the
      step-back technique and randomly divided into 4 groups according to medication
      used: Ca(OH)2 with 0.2% chlorhexidine solution (Group 1), Ca(OH)2 with propylene
      glycol (Group 2), Ca(OH)2 with antibiotic paste (ciprofloxacin, metronidazole)
      and distilled water (Group 3), and Ca(OH)2 with antibiotic paste and propylene
      glycol (Group 4). The samples were stored at 37  degrees C and 100% relative
      humidity for 21 days. The medicaments were removed using 5 mL 1% NaOCl,
      instrumentation with master apical file, 5 mL 1% NaOCl, patency with the K-file
      #10, ultrasonic instrumentation, and 10 mL 17% EDTA-T. The specimens were
      analyzed using scanning electron microscopy and chemical analysis. The Kruskal
      Wallis (alpha = 5%) test showed that were no differences between the experimental
      groups when comparing Ca(OH)2 removal (P = .0951). The chi-square test (alpha =
      5%) indicated a predominance of Ca(OH)2 obstructing dental tubules in all groups.
      On the basis of the methodology applied, it was concluded that the apical dentine
      surface remained equally covered by Ca(OH)2, regardless of the vehicle used.

PMID- 21168350
TI  - Perioperative antibiotic prophylaxis in orthognathic surgery: a systematic review
      and meta-analysis of clinical trials.
AB  - OBJECTIVE: The aim of this study was to investigate whether the use of antibiotic
      prophylaxis in orthognathic surgery can effectively reduce the postoperative
      infection rate. STUDY DESIGN: Electronic databases were searched and reference
      lists checked. Full articles meeting the inclusion criteria were retrieved. Study
      details and outcome data of these reports were statistically analyzed. There was
      no language limitation. RESULTS: Five randomized clinical trials were included in
      the final review process: 4 articles compared the period of prophylactic
      antibiotic usage, and 1 compared the infection prevention effect of different
      types of antibiotics with placebo. Although a significantly higher infection rate
      was found in the placebo group, no significant difference could be found related
      to infection prevention between short- and long-term antibiotic regimen.
      CONCLUSIONS: Prophylactic antibiotic regimen is considered to be useful for
      infection prevention in orthognathic surgery. A single-dose regimen is
      recommended; application for extended postoperative period is not advocated.

PMID- 21168351
TI  - Treatment options for central nervous system cavernous malformations in children.

PMID- 21168352
TI  - Improving the description of salt bridge strength and geometry in a Generalized
      Born model.
AB  - The Generalized Born (GB) solvent model is widely used in molecular dynamics
      simulations because it can be less computationally expensive and it samples
      conformational changes more efficiently than explicit solvent simulations.
      Meanwhile, great efforts have been made in the past to improve its precision and
      accuracy. Previous studies have shown that reducing intrinsic GB radii of some
      hydrogen atoms would improve AMBER GB-HCT solvent model's accuracy on salt
      bridges. Here we present our finding that similar correction also shows dramatic
      improvement for the AMBER GB-OBC solvent model. Potential of mean force and
      cluster analysis for small peptide replica exchange molecular dynamics
      simulations suggested that new radii GB simulation with ff99SB/GB-OBC corrected
      salt bridge strength and achieved significantly higher geometry similarity with
      TIP3P simulation. Improved performance in 60 ns HIV-1 protease GB simulation
      further validated this approach for large systems.

PMID- 21168353
TI  - Studying the catechol binding cavity in comparative models of human dopamine D2
      receptor.
AB  - Obtaining more structural information of human dopamine D(2) receptor may help in
      the design of better therapeutic agents against diseases such as Parkinson. In
      this study attempts have been made to develop a functional model for the catechol
      binding site of the human dopamine D(2) receptor, with two primary models being
      postulated based on the presence of a disulfide bridge in the second
      extracellular loop. The models have been subjected to subsequent molecular
      dynamics simulation and receptor based virtual screening of catechol structures.
      During steady state of the simulations, representative models with the reduced
      disulfide bridge were more capable of discriminating between active and inactive
      catechol structures. It is postulated that similar conformational changes of the
      second extracellular loop observed in 5-HT4 and beta-adrenergic receptors, might
      also take place in the human D(2) receptor during its interaction with agonist
      ligands.

PMID- 21168354
TI  - Low risk of developing Borrelia burgdorferi infection in the south-east of Sweden
      after being bitten by a Borrelia burgdorferi-infected tick.
AB  - OBJECTIVES: The risk of developing Lyme borreliosis (LB) from Borrelia
      burgdorferi sensu lato (Bb)-infected ticks in Sweden is largely unknown. In the
      current study, we investigated the prevalence of Bb in ticks that had bitten
      humans and the risk of developing LB from Bb-infected ticks. METHODS: Health
      questionnaires, blood samples, and ticks were collected from 394 tick-bitten
      study subjects in the County of Ostergotland, Sweden, at the time of the tick
      bite. Questionnaires and blood samples were also collected 3 months later. Ticks
      were screened for Bb DNA with PCR, while sera were analyzed for antibodies
      against Bb using two ELISA assays. Seroconversion, i.e., an at least two-fold
      increase in anti-Bb antibodies after 3 months, was confirmed using a Strip
      Immunoassay. RESULTS: Seventy-five of 397 ticks collected from the study subjects
      were determined to be Bb-positive. Sixty-four of the tick-bitten subjects had
      been bitten by Bb-infected ticks. Four of them showed seroconversion and were
      therefore considered to have an active Bb infection. None of these four subjects
      had sought health care due to symptoms, but one reported symptoms. CONCLUSIONS:
      Our data suggest that the risk of developing LB after being bitten by a Bb
      infected tick is low, and asymptomatic Bb infections appear to be more frequent
      than symptomatic infections.

PMID- 21168355
TI  - Effect of dilute gelatine on the ultrasonic thermally assisted synthesis of nano
      hydroxyapatite.
AB  - A series of nano hydroxyapatite-gelatine composites with different dilute
      solutions of gelatine concentrations were synthesized by a thermally assisted low
      power ultrasonic irradiation method. The gelatine hydroxyapatite, (Gel-HAP)
      nanoparticles were prepared using Ca(NO(3))(2) and KH(2)PO(4) in the presence of
      gelatine in an aqueous solution. The synthesised products were heat treated
      between 100 and 400 degrees C. The effect of the addition of gelatine on the
      nucleation and growth of synthesised nano HAP was investigated. Characterisation
      was performed using X-ray diffraction (XRD), field emission scanning electron
      microscopy (FE-SEM) and Fourier transform infrared spectroscopy (FT-IR). The
      characterisation results indicate that gelatine has been appended to the nano HAP
      forming regular spherical shaped crystals of nano sized Gel-HAP.

PMID- 21168356
TI  - Neighborhood archetypes for population health research: is there no place like
      home?
AB  - This study presents a new, latent archetype approach for studying place in
      population health. Latent class analysis is used to show how the number, defining
      attributes, and change/stability of neighborhood archetypes can be characterized
      and tested for statistical significance. The approach is demonstrated using data
      on contextual determinants of health for US neighborhoods defined by census
      tracts in 1990 and 2000. Six archetypes (prevalence 13-20%) characterize the
      statistically significant combinations of contextual determinants of health from
      the social environment, built environment, commuting and migration patterns, and
      demographics and household composition of US neighborhoods. Longitudinal analyses
      based on the findings demonstrate notable stability (76.4% of neighborhoods
      categorized as the same archetype ten years later), with exceptions reflecting
      trends in (ex)urbanization, gentrification/downgrading, and racial/ethnic
      reconfiguration. The findings and approach is applicable to both research and
      practice (e.g. surveillance) and can be scaled up or down to study health and
      place in other geographical contexts or historical periods.

PMID- 21168357
TI  - Intra-operative 3D guidance and edema detection in prostate brachytherapy using a
      non-isocentric C-arm.
AB  - PURPOSE: Brachytherapy (radioactive seed insertion) has emerged as one of the
      most effective treatment options for patients with prostate cancer, with the
      added benefit of a convenient outpatient procedure. The main limitation in
      contemporary brachytherapy is faulty seed placement, predominantly due to the
      presence of intra-operative edema (tissue expansion). Though currently not
      available, the capability to intra-operatively monitor the seed distribution, can
      make a significant improvement in cancer control. We present such a system here.
      METHODS: Intra-operative measurement of edema in prostate brachytherapy requires
      localization of inserted radioactive seeds relative to the prostate. Seeds were
      reconstructed using a typical non-isocentric C-arm, and exported to a commercial
      brachytherapy treatment planning system. Technical obstacles for 3D
      reconstruction on a non-isocentric C-arm include pose-dependent C-arm
      calibration; distortion correction; pose estimation of C-arm images; seed
      reconstruction; and C-arm to TRUS registration. RESULTS: In precision-machined
      hard phantoms with 40-100 seeds and soft tissue phantoms with 45-87 seeds, we
      correctly reconstructed the seed implant shape with an average 3D precision of
      0.35 mm and 0.24 mm, respectively. In a DoD Phase-1 clinical trial on six
      patients with 48-82 planned seeds, we achieved intra-operative monitoring of seed
      distribution and dosimetry, correcting for dose inhomogeneities by inserting an
      average of over four additional seeds in the six enrolled patients (minimum 1;
      maximum 9). Additionally, in each patient, the system automatically detected
      intra-operative seed migration induced due to edema (mean 3.84 mm, STD 2.13 mm,
      Max 16.19 mm). CONCLUSIONS: The proposed system is the first of a kind that makes
      intra-operative detection of edema (and subsequent re-optimization) possible on
      any typical non-isocentric C-arm, at negligible additional cost to the existing
      clinical installation. It achieves a significantly more homogeneous seed
      distribution, and has the potential to affect a paradigm shift in clinical
      practice. Large scale studies and commercialization are currently underway.

PMID- 21168358
TI  - Diagnostic value of dynamic contrast-enhanced MRI for unilocular cystic-type
      ameloblastomas with homogeneously bright high signal intensity on T2-weighted or
      STIR MR images.
AB  - Typical MR images of ameloblastomas on T2-weighted image (WI) or short inversion
      time inversion-recovery (STIR) show multiple bright high-signal-intensity loci on
      a high-signal-intensity background. Unilocular cystic-type ameloblastomas show
      homogeneously bright high signal intensity on T2WI or STIR as a water-like signal
      intensity. Therefore, it is difficult to distinguish unilocular cystic-type
      ameloblastoma from other cystic lesions such as keratocystic odontogenic tumors,
      radicular cysts (residual cysts) and dentigerous cysts only on the basis of MRI
      signal intensity. In the present study, we evaluated whether contrast-enhanced
      (CE)-T1WI and dynamic CE-MRI (DCE-MRI) could provide additional information for
      differential diagnosis in unilocular cystic-type ameloblastoma. Images from 12
      cases of suspected unilocular cystic-type ameloblastoma were evaluated in the
      present study. Of them, 5 had areas suspected of indicating a solid component on
      T1WI and T2WI (or STIR). Ten had undergone additional CE-T1WI and DCE-MRI. On 5
      of 10 cases of CE-T1WI, a tiny enhancement area was detected. On 6 of 10 DCE
      images, a time-course enhanced area which was suspected to be a solid component
      was detected. CE-T1WI was helpful in the diagnosis of ameloblastoma because the
      tiny enhanced areas were taken to indicate possible solid components. Moreover,
      the rim-enhancement area on CE-T1WI could be divided into small regions of
      interest, and some of these showed slightly increased enhancement on DCE-MRI,
      which was taken to indicate a solid component and/or intramural nodule with focal
      invasion of ameloblastoma tissue. DCE-MRIs of the four remaining cases, which
      provided no clues to the diagnosis of ameloblastoma in the manner of the above
      descriptions, showed thicker rim enhancement than odontogenic cysts. Thus, CE
      T1WI and DCE-MRI were helpful in the differential diagnosis of unilocular cystic
      type ameloblastomas with homogeneously bright high signal intensity on T2WI or
      STIR.

PMID- 21168359
TI  - Long non-coding RNAs and chromatin regulation.
AB  - Microarray analysis and new sequencing technologies have revealed that the
      majority of the genome is transcribed in many eukaryotes. Much of the RNA appears
      to be non-coding and an ongoing debate is how much of a functional role it has.
      Different mechanisms by which ncRNA can be regulatory have been described: direct
      ncRNA effects on transcription; recruitment of chromatin modifiers; formation of
      silent nuclear compartments. These have been documented chiefly in yeasts and
      mammals but examples are now appearing in plants. To date RNA-mediated
      transcriptional silencing studies in plants have focused on siRNAs, but data now
      show longer ncRNAs are also involved in this silencing. Roles for long ncRNAs in
      the phenotypic plasticity of plants are also suggested by whole genome analysis
      showing widespread effects of different external cues on ncRNA expression.

PMID- 21168360
TI  - The role of standardized data and terminological systems in computerized clinical
      decision support systems: literature review and survey.
AB  - INTRODUCTION: Clinical decision support systems (CDSSs) should be seamlessly
      integrated with existing clinical information systems to enable automatic
      provision of advice at the time and place where decisions are made. It has been
      suggested that a lack of agreed data standards frequently hampers this
      integration. We performed a literature review to investigate whether CDSSs used
      standardized (i.e. coded or numerical) data and which terminological systems have
      been used to code data. We also investigated whether a lack of standardized data
      was considered an impediment for CDSS implementation. METHODS: Articles reporting
      an evaluation of a CDSS that provided a computerized advice based on patient
      specific data items were identified based on a former literature review on CDSS
      and on CDSS studies identified in AMIA's 'Year in Review'. Authors of these
      articles were contacted to check and complete the extracted data. A questionnaire
      among the authors of included studies was used to determine the obstacles in CDSS
      implementation. RESULTS: We identified 77 articles published between 1995 and
      2008. Twenty-two percent of the evaluated CDSSs used only numerical data. Fifty
      one percent of the CDSSs that used coded data applied an international
      terminology. The most frequently used international terminology were the ICD
      (International Classification of Diseases), used in 68% of the cases and LOINC
      (Logical Observation Identifiers Names and Codes) in 12% of the cases. More than
      half of the authors experienced barriers in CDSS implementation. In most cases
      these barriers were related to the lack of electronically available standardized
      data required to invoke or activate the CDSS. CONCLUSION: Many CDSSs applied
      different terminological systems to code data. This diversity hampers the
      possibility of sharing and reasoning with data within different systems. The
      results of the survey confirm the hypothesis that data standardization is a
      critical success factor for CDSS development.

PMID- 21168361
TI  - Evaluation of pandemic H1N1 (2009) influenza vaccine in adults with solid tumor
      and hematological malignancies on active systemic treatment.
AB  - BACKGROUND: Over 85% of healthy individuals vaccinated with the pandemic H1N1
      (pH1N1) vaccine achieve seroprotection. OBJECTIVES: We evaluated the safety and
      immunogenicity of pH1N1 vaccine in patients undergoing chemotherapy for
      hematological and solid tumor malignancies. STUDY DESIGN: Adult patients,
      receiving chemotherapy undergoing pH1N1 vaccination at our institution had blood
      samples drawn for CBC (baseline only) and serology prior to and >= 21 days post
      vaccination. HAI antibody testing was performed for pH1N1 (A/California/7/2009
      strain) and seasonal H1 (A/Brisbane/59/07 strain). Seroprotection was defined as
      a pH1N1 antibody titre >= 1:40 and seroconversion as an antibody titre >4 *
      baseline. Patients completed a symptom diary card. RESULTS: Paired samples were
      available for 46 patients (20 solid tumor, 26 hematological), median age 56
      (range 23-76) years. The seroprotective rate post-vaccination for solid tumors
      was 50% compared to 27% for hematological malignancy (p=0.11), respective
      seroconversion rates were 45% and 19% (p=0.06). In patients with solid tumors
      vaccination mid cycle resulted in the highest pH1N1 titres, although timing and
      blood count were not associated with seroconversion or seroprotection. For
      hematological patients, a normal leukocyte count and vaccination at the beginning
      of a cycle were associated with higher rates of seroconversion (p <= 0.05).
      Addition of rituximab to chemotherapy resulted in a failure to seroconvert
      (p=0.05). Vaccination was well tolerated by all patients. CONCLUSIONS: Although
      well tolerated, the seroprotection rate following pH1N1 vaccination is lower than
      that would be expected. Further investigation into immunization strategies in
      patients receiving chemotherapy is required.

PMID- 21168362
TI  - The vestibular evoked-potential profile of Meniere's disease.
AB  - OBJECTIVE: To define the ocular and cervical vestibular evoked myogenic potential
      (oVEMP and cVEMP) profile in Meniere's Disease (MD), we studied air-conducted
      (AC) sound and bone-conducted vibration (BCV)-evoked responses in 77 patients and
      35 controls. METHODS: oVEMPs were recorded from unrectified infra-orbital surface
      electromyography (EMG) during upward gaze. cVEMPs were recorded from rectified
      and unrectified sternocleidomastoid EMG during head elevation against gravity.
      Responses to AC clicks delivered via headphones and BC forehead taps delivered
      with a mini-shaker (bone-conduction vibrator) and a triggered tendon-hammer were
      recorded. RESULTS: In clinically definite unilateral MD (n=60), the prevalence of
      unilateral VEMP abnormalities was 50.0%, 10.2% and 11.9% for click, minitap and
      tendon-hammer evoked oVEMPs, 40.0%, 22.8% and 10.7% for click, minitap and tendon
      hammer evoked cVEMPs. The most commonly observed profile was abnormality to AC
      stimulation alone (33.3%), followed by abnormalities to both AC and BCV stimuli
      (26.7%). Isolated abnormalities to BCV stimuli were rare (5%) and limited to the
      minitap cVEMP. The prevalence of abnormalities for each of the AC VEMPs was
      significantly higher than for any one BCV VEMP. For click cVEMP, click oVEMP and
      minitap cVEMP, average Reflex Asymmetry Ratios (AR) were significantly higher in
      MD compared with controls. Test results for AC cVEMP, AC oVEMP, minitap cVEMP and
      caloric asymmetry were significantly correlated with hearing loss. CONCLUSIONS:
      Predominance of abnormalities in oVEMP and cVEMP responses to AC sound is
      characteristic of MD and indicative of saccular involvement. SIGNIFICANCE: This
      pattern of VEMP abnormalities may enable separation of Meniere's disease from
      other peripheral vestibulopathies.

PMID- 21168363
TI  - The carcinogenic potential of nanomaterials, their release from products and
      options for regulating them.
AB  - A summary of a critical review by a working group of the German Federal
      Environment Agency and the German Federal Institute for Risk Assessment on the
      carcinogenic potential of nanomaterials is presented. After a critical review of
      the available data, we conclude that the potential carcinogenic risk of
      nanomaterials can currently be assessed only on a case-by-case basis. There is
      certain evidence that different forms of CNTs (carbon nanotubes) and nanoscale
      TiO(2) particles may induce tumours in sensitive animal models. It is assumed
      that the mode of action of the inhalation toxicity of asbestos-like fibres and of
      inhalable fractions of biopersistent fine dusts of low toxicity (nano-TiO(2)) is
      linked to chronic inflammatory processes. Existing epidemiological studies on
      carcinogenicity for these manufactured nanomaterials are not sufficiently
      conclusive. Generally speaking, the database is not adequate for an assessment of
      the carcinogenic potential of nanomaterials. Whereas a number of studies provide
      evidence of a nano-specific potential to induce tumours, other studies did not.
      This is possibly due to insufficient characterisation of the test material,
      difference in the experimental design, the use of different animal models and
      species and/or differences in dosimetry (both with regard to the appropriate dose
      metric and the estimated effective dose quantities). An assessment of the
      carcinogenic potential and its relevance for humans are currently fraught with
      uncertainty. Furthermore, the nano-specificity of the carcinogenic effects
      observed cannot be conclusively evaluated. Specific carcinogenic effects of
      nanomaterials may be both quantitative and qualitative. In quantitative terms,
      the carcinogenic effects of nanoparticles are thought to be simply more
      pronounced compared to the corresponding bulk material (due, for example, to the
      considerably larger surface area and higher number of particles relative to the
      mass concentration). On the other hand, certain nano-properties such as small
      size, shape and reactivity, retention time and distribution in the body after
      overcoming biological barriers, as well as subcellular and molecular interactions
      may play a role in determining the toxicity in qualitative terms, i.e. the
      carcinogenic potential of the nanomaterial and the non-nanoscale comparison
      substance may be fundamentally different. All of these factors leave no doubt
      about the fact that there is a great need for research in this area and that new
      standardised test methods need to be developed or existing ones adapted at the
      very least to achieve valid answers regarding the carcinogenic potential of
      nanomaterials. Global production of nanomaterials is set to increase in the years
      to come, and new materials with new properties will be developed, so that greater
      human exposure to them must be anticipated. No reliable conclusions can currently
      be drawn about exposure to nanoparticles and their release from products.
      Firstly, there are substantial deficits in information about the processing of
      nanomaterials in products and preparations. Secondly, there are only a small
      number of studies on nanoparticle release, and reliable techniques for measuring
      and monitoring nanomaterials in different environmental media are still being
      developed which is both complex and costly. Despite the uncertainties, the
      findings to date on the carcinogenic potential of nanomaterials must be taken
      seriously, and precautionary measures to minimise exposure should go hand in hand
      with the development of a comprehensive and conclusive toxicological methodology
      and testing procedure for nanostructured materials that includes all possible
      exposure routes. With regard to possible legal classification of nanomaterials
      and the transferability of classifications of their non-nanomaterial
      counterparts, we believe it is necessary to have separate procedures for nano and
      non-nano forms. Furthermore, criteria for evaluating nano-specific carcinogenic
      properties should be constantly updated and adapted to the state of knowledge.
      There is a need here for amendments to be made to EU legislation, as currently
      nanoforms do not represent a separate category of substance in their own right.

PMID- 21168364
TI  - Emerging roles of basophils in protective immunity against parasites.
AB  - Basophils, the least common type of granulocyte, have long been considered as
      minor effector cells in allergic responses because of their ability to release
      allergy-inducing chemical mediators such as histamine and leukotriene C4.
      However, it is unlikely that many animal species evolutionarily conserve
      basophils to only elicit allergic responses without any host-beneficial function.
      The study of basophils has been hampered by their rarity and difficult
      identification, as well as the lack of suitable animal models. Recent studies
      using novel analytical tools, including basophil-depleting antibodies and
      genetically engineered mice deficient only in basophils, have illuminated the
      crucial and nonredundant roles for basophils in protective immunity against both
      ecto- and endoparasites.

PMID- 21168365
TI  - The impact of genetic diversity in protozoa on molecular diagnostics.
AB  - Detection of intestinal parasitic protists, commonly referred to as 'intestinal
      protozoa,' by PCR is increasingly used not only for identification or
      confirmation but also as a first-line diagnostic tool. Apart from the ability to
      sample correctly and extract parasite DNA directly from faeces, primer and probe
      specificity and sensitivity affect predictive values and hence the utility of
      diagnostic assays. Molecular characterization of intestinal protists is necessary
      to design primers and probes because this is the basic material for current and
      future improved diagnostic PCRs for either detecting all genetic variants or
      specifically differentiating among such variants. As an example, this paper
      highlights the existence of interspecific and intraspecific genetic diversity
      among intestinal, unicellular parasites and its implications for nucleic acid
      based diagnostic assays.

PMID- 21168366
TI  - Anthelmintic resistance in nematode parasites of cattle: a global issue?
AB  - Acceptable performance of grazing cattle frequently depends on the availability
      of effective broad-spectrum anthelmintics to remove, or prevent infection with,
      gastrointestinal nematodes. This control is increasingly threatened by
      populations of nematodes resistant to the most commonly used anthelmintics.
      Although this appears to have developed more slowly than in nematodes infecting
      small ruminants, the number of reports in the literature over the past five years
      suggests a rapidly escalating problem. This review discusses this literature,
      several issues unique to cattle parasitism and anthelmintics, and how previous
      research in small ruminants can improve the management of anthelmintic resistance
      in cattle.

PMID- 21168367
TI  - Developing supervision skills through peer learning partnership.
AB  - Oslo University College, Faculty of Nursing places undergraduate students in peer
      learning partnerships: 3rd year students as tutors, and 1st year students as
      tutees during practical skill learning. A study was designed to investigate this
      peer learning project. One of the research questions in particular on the role of
      the tutors: How do 3rd year nursing students carry out their role as supervisors
      for 1st year students in the skills laboratory? The study had an exploratory
      design. Qualitative data was gathered by three members of a research team, using
      video recordings of the supervised sessions and focus group interviews with both
      1st and 3rd year students. Data collection was repeated in 2006-2007-2008 in
      different groups of students. Four identified themes illustrate how the 3rd year
      students supervise during the performance of the procedures in the skills
      laboratory: Observe and guide, supportive attitude, identify with the patient,
      focus on theoretical knowledge. The results of this study indicate that apart
      from enhancing practical skill learning in 1st year students, the assignment in
      the skill laboratory also provided an arena for developing competence in
      supervision in third year students.

PMID- 21168368
TI  - Head-to-head comparison of pandemic influenza vaccines.

PMID- 21168370
TI  - The optometrist's role in the management of hypertensive crises.
AB  - BACKGROUND: In hypertensive crises, ocular findings are pivotal to making correct
      management decisions. Joint National Committee on Prevention, Detection, and
      Treatment of High Blood Pressure (JNC-7) guidelines define hypertensive crises as
      blood pressure greater than 180/120 mmHg associated with signs or symptoms of
      target organ damage. Urgent cases are those without optic disc edema but that
      necessitate control within 24 to 72 hours. Emergent cases are those with optic
      disc edema, also known as malignant hypertension, demanding control within 1 to 6
      hours. CASE REPORTS: Two cases are illustrated, as might be seen in optometric
      offices, of severe stage II hypertension. In case 1, the acute elevation of blood
      pressure (220/110 mmHg), was assessed as an urgent case and was correctly managed
      with the primary care provider through outpatient care. The second case of acute
      elevation of blood pressure (250/150 mmHg) and ocular findings of severe
      hypertensive retinopathy was sent as an emergent case to the emergency room.
      CONCLUSION: These cases exemplify optometric in-office decisions to effectively
      manage urgent and emergent cases of hypertensive crises. Utilizing an urgent
      versus emergent classification of retinopathy can lead to the appropriate
      management decision for these patients.

PMID- 21168369
TI  - Immunogenicity and safety of a two-dose schedule of whole-virion and AS03A
      adjuvanted 2009 influenza A (H1N1) vaccines: a randomised, multicentre, age
      stratified, head-to-head trial.
AB  - BACKGROUND: Effective antigen-sparing vaccines are needed to confront pandemic
      influenza. Whole-virion and oil-in-water adjuvanted vaccines are the most
      effective formulations against H5N1 avian influenza. We assessed the safety and
      immunogenicity in adults in the UK of pandemic H1N1 whole-virion vaccine and oil
      in-water adjuvanted vaccine purchased by the UK government in 2009. METHODS: In
      our randomised, observer-blind, parallel-group, controlled trial, healthy adults
      aged 18-44 years, 45-64 years, and 65 years and older (from Oct 19, to Nov 12,
      2009) received two doses of vaccine given 21 days apart: either 7.5 MUg of
      haemagglutinin formulated as whole-virion vaccine, or 3.75 MUg of haemagglutinin
      formulated as split-virion vaccine with AS03(A) oil-in-water adjuvant. Assignment
      was by a computer-generated code, with random permuted blocks of two, four, and
      six. All participants and investigators were unaware of vaccine assignments. The
      trial was done at three hospitals in the UK. We measured antibody titres with a
      haemagglutination-inhibition assay at baseline; 7, 14, and 21 days after each
      vaccination; and at 6 months after the first dose. Primary outcome was vaccine
      immunogenicity of the full analysis set by the EU Committee of Human Medicinal
      Products licensing criteria. This study is registered with ISRCTN, number
      ISRCTN92328241. FINDINGS: At day 0, baseline antibody (titre >=1/8) was detected
      in 44 (13%) of 347 participants. Sera from 95% to 98% of participants were
      assessed for immunogenicity on days 7, 14, 21, 28, 35, and 42, and at 6 months.
      On day 21 after one dose of adjuvanted AS03(A) or whole-virion vaccine, 63 (94%,
      95 CI 85.4-98.4) of 67 and 50 (71%, 59.4-81.6) of 70 participants aged 18-44
      years, 51 (77%, 65.3-86.7) of 66 and 26 (39%, 27.1-51.5) of 67 aged 45-64 years,
      and 19 (51%, 34.4-68.1) of 37 and 11 (32%, 17.4-50.5) of 34 aged 65 years or
      older had titres of 1:40 or greater. On day 42 (21 days after the second dose),
      64 (100%, 94.4-100) of 64 and 49 (73%, 60.9-83.2) of 67 participants aged 18-44
      years, 59 (91%, 81.0-96.5) of 65 and 29 (43.9%, 31.7-56.7) of 66 aged 45-64
      years, and 28 (76%, 58.8-88.2) of 37 and 12 (36%, 20.4-54.9) of 33 aged 65 years
      or older had titres of 1/40 or greater. At 6 months, 62 (98%, 91.5-100) of 63 and
      54 (78%, 66.7-87.3) of 69 participants aged 18-44 years, 54 (82%, 70.4-90.2) of
      66 and 37 (55%, 42.6-67.4) of 67 aged 45-64 years, and 21 (57%, 39.5-72.9) of 37
      and 10 (29%, 15.1-47.5) of 34 aged 65 years or older had titres of 1/40 or
      greater. There were no vaccine-related serious adverse events. Whole-virion
      vaccine was associated with fewer local and systemic reactions than adjuvanted
      vaccine. INTERPRETATION: AS03(A)-adjuvanted vaccine was more immunogenic against
      pandemic influenza A H1N1 virus than whole-virion vaccine and offers greater
      antigen-sparing capacity. A two-dose strategy should be considered for older
      people. FUNDING: Department of Health, National Institute for Health Research
      Evaluation, Trials and Studies Coordinating Centre.

PMID- 21168371
TI  - GC-MS analysis of bisphenol A in human placental and fetal liver samples.
AB  - A method based on extraction with acetonitrile, followed by solid-phase
      extraction, derivatization with acetic anhydride, and isotope dilution gas
      chromatography-mass spectrometry (GC-MS) analysis was applied to determine levels
      of free and conjugated BPA in human tissues. beta-Glucuronidase was used to de
      conjugate the glucuronized BPA in the samples. The method was validated using
      various animal organ meat samples including pork liver and kidney, beef and calf
      liver, chicken liver and heart; recoveries were from 85% to 112% at two spiking
      levels. The average method limit of quantification (LOQ) was estimated at 0.77
      ng/g for placenta samples and 1.2 ng/g for fetal liver samples based on 10 times
      the signal to noise ratio. BPA was detected in all animal tissue samples, with
      concentrations ranging from 1.8 ng/g in beef and calf livers to 17.1 ng/g in pork
      kidney. The method was used successfully to determine both free and conjugated
      BPA levels in human placental and fetal liver tissue samples. BPA was detected in
      86% of the placental samples; concentrations of free BPA in the positive samples
      ranged from 0.60 ng/g to as high as 64 ng/g with an average of 9.5 ng/g and a
      median of 3.0 ng/g, and conjugated BPA was as high as 7.8 ng/g. BPA was also
      detected in most of the fetal liver samples (57%); concentrations of free BPA in
      the positive samples ranged from 1.3 to 27 ng/g with an average of 8.5 ng/g and a
      median of 3.2 ng/g. Conjugated BPA was also detected in most of the liver samples
      analysed for total BPA, ranging from 0.64 to 20 ng/g with an average of 3.9 ng/g
      and a median of 1.5 ng/g. This study, while primarily designed as a method
      validation, has demonstrated that BPA can be detected in human fetal liver
      samples as early as the third month of fetal life. Further work will be conducted
      to validate these preliminary findings.

PMID- 21168373
TI  - Determination of 1,25-dihydroxyvitamin D2 in rat serum using liquid
      chromatography with tandem mass spectrometry.
AB  - Vitamin D therapy is widely used for the treatment of hyperparathyroidism
      associated with chronic renal failure in renal disease patients. The vitamin D
      prodrug, 1alpha-hydroxyvitamin D(2) (1alpha(OH)D(2)), is used for the treatment
      of the end stage renal disease patients who as a result of impaired kidney
      function cannot convert the naturally occurring vitamin D to the active hormonal
      form namely 1,25-dihydroxyvitamin D(2) (1,25(OH)(2)D(2)). The systemic
      circulating levels of this active form are in the pg/mL range and represent a
      significant bioanalytical challenge for therapeutic monitoring. Liquid
      chromatography with tandem mass spectrometry (LC-MS/MS) is considered the gold
      standard for the selective and sensitive determination of small molecule
      therapeutics in biological matrices. However, the reported LC-MS/MS bioanalytical
      assays for 1,25(OH)(2)D(2) suffer from extensive sample preparation procedures or
      derivatization protocols to achieve the requisite sensitivity and selectivity. In
      this paper, we describe an assay that employs 96-well plate solid phase
      extraction sample preparation combined with highly sensitive LC-MS/MS
      instrumentation. The utility of ultra high pressure liquid chromatography to
      reduce the analytical run time was also demonstrated. Employing this assay a
      lower limit of quantitation of 25.0 pg/mL using 300 MUL sample aliquot of rat
      serum was achieved with linearity obtained over the range of 25.0-1000 pg/mL.
      Both intra-day and inter-day coefficients of variation were <15% and accuracy
      across the assay range was within 100+/-7.24%. The application of the assay was
      demonstrated for the analysis of 1,25(OH)(2)D(2) rat serum samples to support
      pharmacokinetic studies conducted at doses down to sub-microgram per kilogram of
      1alpha(OH)D(2).

PMID- 21168372
TI  - Profiling sterols in cerebrotendinous xanthomatosis: utility of Girard
      derivatization and high resolution exact mass LC-ESI-MS(n) analysis.
AB  - In this study we profile free 3-oxo sterols present in plasma from patients
      affected with the neurodegenerative disorder of sterol and bile acid metabolism
      cerebrotendinous xanthomatosis (CTX), utilizing a combination of charge-tagging
      and LC-ESI-MS(n) performed with an LTQ-Orbitrap Discovery instrument. In
      addition, we profile sterols in plasma from 24-month-old cyp27A1 gene knockout
      mice lacking the enzyme defective in CTX. Charge-tagging was accomplished by
      reaction with cationic Girard's P (GP) reagent 1-(carboxymethyl) pyridinium
      chloride hydrazide, an approach uniquely suited to studying the 3-oxo sterols
      that accumulate in CTX, as Girard's reagent reacts with the sterol oxo moiety to
      form charged hydrazone derivatives. The ability to selectively generate GP-tagged
      3-oxo-4-ene and 3-oxo-5(H) saturated plasma sterols enabled ESI-MS(n) analysis of
      these sterols in the presence of a large excess (3 orders of magnitude) of
      cholesterol. Often cholesterol detected in biological samples makes it
      challenging to quantify minor sterols, with cholesterol frequently removed prior
      to analysis. We derivatized plasma (10 MUl) without SPE removal of cholesterol to
      ensure detection of all sterols present in plasma. We were able to measure 4
      cholesten-3-one in plasma from untreated CTX patients (1207+/-302 ng/ml, mean+/
      SD, n=4), as well as other intermediates in a proposed pathway to 5alpha
      cholestanol. In addition, a number of bile acid precursors were identified in
      plasma using this technique. GP-tagged sterols were identified utilizing high
      resolution exact mass spectra (+/-5 ppm), as well as MS(2) ([M](+)->) spectra
      that possessed characteristic neutral loss of 79Da (pyridine) fragment ions, and
      MS(3) ([M](+)->[M-79](+)->) spectra that provided additional structurally
      informative fragment ions.

PMID- 21168374
TI  - Management of warfarin-associated coagulopathy in patients with acute
      gastrointestinal bleeding: a cross-sectional physician survey of current
      practice.
AB  - BACKGROUND: The management of vitamin K antagonists (VKAs) associated
      coagulopathy is a cornerstone of pre-endoscopic assessment of anticoagulated
      patients presenting with acute gastrointestinal bleeding. AIMS: To evaluate
      physician attitudes in the management of VKAs-associated coagulopathy in patients
      presenting with gastrointestinal bleeding and to assess their compliance to
      current practice guidelines. DESIGN: Cross sectional physician web-based survey
      amongst regional members of three Italian Gastroenterological Societies (AIGO,
      SIED, SIGE) practicing in academic medical centres or community hospitals.
      Physicians were asked to provide management preferences in four hypothetical case
      scenarios describing patients with warfarin-associated coagulopathy presenting
      with gastrointestinal bleeding of varying severity. RESULTS: A total of 105 out
      of 238 (48%) members responded; mean age+/-SD: 46.3+/-9.8 years, 68% male. The
      adherence to practice guidelines for the reversal of warfarin-induced
      anticoagulation ranged from 24% to 86% and it was not dependent on age, years and
      type of specialisation, hospital setting and active performance of "on call"
      emergency endoscopy or not. CONCLUSIONS: There is a considerable variability
      amongst physicians in the management of gastrointestinal bleeding patients with
      VKAs-associated coagulopathy and a poor compliance to practice guidelines. These
      data indicate that better education is needed in this area.

PMID- 21168376
TI  - [Difficult to manage diabetes mellitus associated with generalized congenital
      lipodystrophy. Report of two cases].
AB  - Generalized congenital lipodystrophy or Berardinelli-Seip Syndrome is a rare
      autosomal recessive condition characterized by the absence of adipose tissue and
      eventually a defect in leptin synthesis. Affected subjects tend to show a
      classical phenotype with acromegaloid appearance, generalized atrophy of
      subcutaneous adipose tissue with muscular hypertrophy, acanthosis nigricans,
      hepatomegaly and prominent abdomen. From metabolic point of view and as a
      consequence of leptin absence, hypertriglyceridemia leading to hepatic steatosis
      and insulin resistance may appear. Two cases of unrelated subjects affected of
      generalized congenital lipodystrophy are presented. Both developed difficult-to
      manage diabetes mellitus and were treated with high doses of insulin. In both
      cases early microvascular complications were present. A mutation for LMNA gene
      was found in one of the subjects.

PMID- 21168375
TI  - Lipopolysaccharide-induced intestinal motility disturbances are mediated by c-Jun
      NH2-terminal kinases.
AB  - BACKGROUND: Lipopolysaccharide (LPS) is a causative agent of sepsis. Many
      alterations, such as intestinal motility disturbances, have been attributed to
      LPS. AIMS: Here we investigated the role of c-Jun NH(2)-terminal kinases (JNK) in
      the effect of LPS on intestinal motility, the oxidative stress status and the
      cyclooxygenese-2 (COX-2) expression. METHODS: Rabbits were injected with either
      (1) saline, (2) LPS, (3) SP600125, a specific JNK inhibitor, or (4) SP600125+LPS.
      Duodenal contractility was studied in an organ bath. The formation of products of
      oxidative damage to proteins (carbonyls) and lipids [malondialdehyde (MDA) and 4
      hydroxyalkenals (4-HDA)] was quantified by spectrophotometry in the intestine and
      plasma. The protein expression of p-JNK, total JNK, and COX-2 was measured by
      Western blot, and p-JNK was localized by immunohistochemistry. RESULTS: LPS
      decreased the contractions evoked by acetylcholine and prostaglandin E(2) and KCl
      induced contractions. LPS increased phospho-JNK and COX-2 expressions and the
      levels of carbonyls and MDA+4-HDA. SP600125 blocked the effect of LPS on the
      acetylcholine, prostaglandin E(2), and KCl-induced contractions, the levels of
      carbonyls and MDA+4-HDA, and the p-JNK and COX-2 expressions. p-JNK was detected
      in the smooth muscle cells of duodenum. CONCLUSION: Our results suggest that JNK
      is involved in the mechanism of action of LPS in the intestine.

PMID- 21168377
TI  - [Spectrum of primary immunodeficiencies in a tertiary hospital over a period of
      10 years].
AB  - INTRODUCTION: More than 200 primary immunodeficiencies (PID) have been described
      and about 60% present during childhood. Early diagnosis and treatment have been
      shown to improve patient outcome. AIM: Analysis of patients with a PID diagnosed
      in a paediatric tertiary care hospital-referral centre over a period of 10 years.
      PATIENTS AND METHODS: Medical records of all paediatric patients followed up in
      our unit were retrospectively reviewed. Clinical and epidemiological features,
      laboratory tests, therapy and outcome were analysed. RESULTS: One hundred and
      eighty nine patients were followed up in this period of time. Antibody disorders
      were the most common diagnosis. In our series, clinical presentation at diagnosis
      were: recurrent respiratory infections in selective IgA deficiency and common
      variable immunodeficiency (CVID) patients, failure to thrive and opportunistic
      infections (mainly viral infections) in patients with severe combined
      immunodeficiency (SCID), skin abscesses (Staphylococcus aureus, Serratia spp.)
      and complicated pneumonia (Aspergillus spp., Rhodococcus equi) in chronic
      granulomatous disease, congenital heart disease and consistent phenotype in 22q11
      deletion syndrome, skin abscesses and ecthyma gangrenosum in severe congenital
      neutropenia and opportunistic infections and sepsis (Pseudomonas aeruginosa) in
      children with X-linked agammaglobulinaemia (XLA). Lymphoproliferative disorders
      were common in CVID. No malignancies were observed during this period. One
      patient with XLA developed chronic encephalitis. All patients with CVID and XLA
      were receiving immunoglobulin replacement therapy (8 intravenous and 14 (since
      2006) subcutaneous route) and in all but two SCID patients, stem cell
      transplantation was performed. Outcome was good in most of them except 8 SCID (2
      prior and 6 after transplantation), 3 Wiskott-Aldrich syndrome, 1 complete
      DiGeorge, 1 chronic granulomatous disease and 1 ataxia-telangiectasia patients
      who died during follow-up. CONCLUSION: The vast majority of patients included in
      this series presented with typical clinical features; therefore, basic knowledge
      of these entities in primary care and collaboration with hospital referral
      centres should allow a large number of PID in children to be diagnosed at an
      early stage, leading to proper treatment and monitoring, and therefore
      improvement of patient prognosis.

PMID- 21168378
TI  - Liposuction: a review of principles and techniques.
AB  - For one of the most commonly performed aesthetic procedures, liposuction has a
      somewhat mixed reputation. This may result from suboptimal technical
      comprehension and/or poor patient selection. It has also attracted strong
      commercial pressure from manufacturers of new, sometimes less assiduously
      evaluated, technologies. Liposuction is not a panacea for obesity and patients
      are not always cognisant of this. On the other hand, it can produce highly
      satisfactory outcomes for well-selected patients and anatomical areas when
      performed by appropriately-trained operators using properly selected
      technologies. Although introduced by the Europeans, liposuction was
      enthusiastically adopted by the North Americans, yet seems to have excited little
      scientific interest in the UK, despite widespread use. Given the numerous
      techniques and recent advances, a review may be timely.

PMID- 21168379
TI  - A simplified technique for the management of fat necrosis in autologous breast
      reconstruction.

PMID- 21168380
TI  - [Acute kidney injury: from concept to practice].
AB  - Definition and classification of acute renal failure evolved in recent years. The
      acronym "Acute Kidney Injury" replaces "Acute Renal Failure". The RIFLE
      classification spreads the AKI in three degrees of severity, and two degrees of
      disease duration. The group Acute Kidney Injury Network refines this
      classification into three stages, to improve the sensitivity in detecting
      moderate forms. The epidemiology of AKI remains imprecise. In the ICU, more than
      30% of patients suffered from AKI, often in a context of multiple organs failure.
      In addition to serum creatinine and urine output, new biomarkers can be assessed.
      Their early detection should enable a clearer distinction between "acute tubular
      necrosis" and other causes of AKI, but also to distinguish patients at risk for
      pejorative evolution of renal function. The management of AKI based on an optimal
      resuscitation. The administration of loop diuretics or low dose dopamine showed
      no benefit. Hydration in prevention of the contrast-induced nephropathy is
      confirmed. The role of acetylcysteine must be determined. The ideal time to
      initiate a renal replacement therapy and the choice of the technique remain
      unresolved. The same goes for the dose of dialysis administered. A systematic
      application of an algorithm, such as proposed by Bagshow would make comparisons
      easier and the realisation of multicenter studies will help to clarify these
      points.

PMID- 21168382
TI  - Expanding the ProteOn XPR36 biosensor into a 36-ligand array expedites protein
      interaction analysis.
AB  - Here we demonstrate methods to expand the throughput of the ProteOn XPR36
      biosensor allowing for the simultaneous kinetic characterization of several
      multiplexed formats, such as 36 disparate antibodies targeting the same antigen,
      and facilitating detailed epitope binning and mapping studies. The kinetic rate
      constants determined by these methods correlated with those obtained on Biacore
      2000 and the absolute parameter values obtained on the ProteOn's alginate-based
      GLC chip agreed closer with those from Biacore's flat C1 chip than Biacore's
      dextran-based CM4 chip. Pairwise epitope binning data from the ProteOn 36-ligand
      array format and those generated on an orthogonal array-based biosensor, the
      Octet QK384, gave similar results. In an epitope mapping study using biotinylated
      peptides, all three biosensor platforms were similar in their ability to identify
      antibodies that bound to linear epitopes. We apply alternative formats of the
      ProteOn array that enable a significantly higher number of assays to be conducted
      simultaneously than previously anticipated on this platform.

PMID- 21168381
TI  - Adipose tissue-derived mesenchymal stem cell-based liver gene delivery.
AB  - BACKGROUND & AIMS: The adipose tissue represents an accessible, abundant, and
      replenishable source of adult stem cells for potential applications in
      regenerative medicine. Adipose tissue-derived mesenchymal stem cells (AT-MSCs)
      resemble bone marrow-derived mesenchymal stem cells (BM-MSCs) with respect to
      morphology, immune-phenotype, and multiple differentiation capability. In the
      present study, we investigated the feasibility of AT-MSC-based liver gene
      delivery for the treatment of alpha 1-antitrypsin deficiency. METHODS: Mouse AT
      MSCs were transduced by rAAV vectors and transplanted into the mouse liver.
      RESULTS: We showed that AT-MSCs can be transduced by recombinant adeno-associated
      viral vector serotype 1 (rAAV1-CB-hAAT). After transplanting to the mouse liver,
      ex vivo transduced AT-MSCs expressed the transgene product, human alpha 1
      antitrypsin (hAAT). Importantly, serum levels of hAAT were sustained and no anti
      hAAT antibody was detected in any recipients. CONCLUSIONS: These results
      demonstrated that AT-MSCs can be transduced by rAAV vectors, engrafted into
      recipient livers, contribute to liver regeneration, and serve as a platform for
      transgene expression without eliciting an immune response. AT-MSC-based gene
      therapy presents a novel approach for the treatment of liver diseases, such as
      AAT deficiency.

PMID- 21168383
TI  - Quantification of ultra-trace molybdenum using 4-amino-5-hydroxynaphthalene-2,7
      disulfonic acid monosodium salt as a chromogenic probe.
AB  - A simple, ultrasensitive, nonextractive spectrophotometric method has been
      developed for the assay of Mo(VI), which involves Mo-catalyzed oxidation of 4
      amino-5-hydroxynaphthalene-2,7-disulfonic acid monosodium salt (AHNDSA) by
      H(2)O(2) in acetic acid/sodium acetate buffer yielding an intense pink colored
      product with lambda(max) of 540 nm. Beer's law is obeyed in the range of 10-240
      ng/ml with molar absorptivity of 3.0137*10(5)L mol(-1)cm(-1). The LOD and LOQ
      were found to be 0.7696 and 2.565 ng/ml, respectively. The applicability of the
      method toward water and biological samples was tested and statistically compared
      with a reference method.

PMID- 21168384
TI  - Overexpression of KAI1 induces autophagy and increases MiaPaCa-2 cell survival
      through the phosphorylation of extracellular signal-regulated kinases.
AB  - KAI1, a metastasis-suppressor gene belonging to the tetraspanin family, is known
      to inhibit cancer metastasis without affecting the primary tumorigenicity by
      inhibiting the epidermal growth factor (EGF) signaling pathway. Recent studies
      have shown that hypoxic conditions of solid tumors induce high-level autophagy
      and KAI1 expression. However, the relationship between autophagy and KAI1 remains
      unclear. By using transmission electron microscopy, confocal microscopy, and
      Western blotting, we found that KAI1 can induce autophagy in a dose- and time
      dependent manner in the human pancreatic cell line MiaPaCa-2. KAI1-induced
      autophagy was confirmed by the expression of autophagy-related proteins LC3 and
      Beclin 1. KAI1 induces autophagy through phosphorylation of extracellular signal
      related kinases rather than that of AKT. KAI1-induced autophagy protects MiaPaCa
      2 cells from apoptosis and proliferation inhibition partially through the
      downregulation of poly [adenosine diphosphate (ADP)-ribose] polymerase (PARP)
      cleavage and caspase-3 activation.

PMID- 21168385
TI  - An efficient delivery of DAMPs on the cell surface by the unconventional
      secretion pathway.
AB  - Damage-associated molecular patterns (DAMPs) are signals released from dying
      cells evoking the immune system response in several inflammatory disorders. In
      normal situations, many of DAMPs are nuclear or cytosolic proteins with defined
      intracellular function, but they could be found on the cell surface following
      tissue injury. The biological function of the translocated DAMPs is still not
      well known and an efficient delivery of these molecules on the cell surface is
      required to clarify their biological effects. In this study, we demonstrated that
      an unclassical secretory signal peptide, N-terminal 18 amino acids of HASPB
      (HASPB-N18), could efficiently deliver Hsp60, Hsp70, and HMGB1 on the cell
      surface. Furthermore, the delivery of these molecules on the cell surface by
      HASPB-N18 is not limited to a special cell line because several cell lines could
      use this delivery signal to deliver these molecules on the cell surface.
      Moreover, we demonstrated that Hsp60 on the cell surface delivered by HASPB-N18
      could be recognized by a soluble form of LOX-1, which implies that DAMPs on the
      cell surface delivered by HASPB-N18 have a proper conformation during transport.
      Therefore, delivery of DAMPs by HASPB-N18 is a reliable model to further
      understand the biological significance of DAMPs on the cell surface.

PMID- 21168386
TI  - Zyxin phosphorylation at serine 142 modulates the zyxin head-tail interaction to
      alter cell-cell adhesion.
AB  - Zyxin is an actin regulatory protein that is concentrated at sites of actin
      membrane association, particularly cell junctions. Zyxin participates in actin
      dynamics by binding VASP, an interaction that occurs via proline-rich N-terminal
      ActA repeats. An intramolecular association of the N-terminal LIM domains at or
      near the ActA repeats can prevent VASP and other binding partners from binding
      full-length zyxin. Such a head-tail interaction likely accounts for how zyxin
      function in actin dynamics, cell adhesion, and cell migration can be regulated by
      the cell. Since zyxin binding to several partners, via the LIM domains, requires
      phosphorylation, it seems likely that zyxin phosphorylation might alter the head
      tail interaction and, thus, zyxin activity. Here we show that zyxin point mutants
      at a known phosphorylation site, serine 142, alter the ability of a zyxin
      fragment to directly bind a separate zyxin LIM domains fragment protein. Further,
      expression of the zyxin phosphomimetic mutant results in increased localization
      to cell-cell contacts of MDCK cells and generates a cellular phenotype, namely
      inability to disassemble cell-cell contacts, precisely like that produced by
      expression of zyxin mutants that lack the entire regulatory LIM domain region.
      These data suggest that zyxin phosphorylation at serine 142 results in release of
      the head-tail interaction, changing zyxin activity at cell-cell contacts.

PMID- 21168387
TI  - Similarity and dissimilarity of thiols as anti-nitrosative agents in the nitric
      oxide-superoxide system.
AB  - Concomitant production of nitric oxide and superoxide in biological systems has
      been proposed to generate numerous reactive oxygen and nitrogen species that
      cause oxidative and nitrosative stress. Thiols, especially glutathione, play an
      important role in cellular defense against radical species. In the present study,
      we investigated and compared the anti-nitrosative activity of a wide range of
      thiols in a simplified chemical system of co-generated nitric oxide and
      superoxide. Of the 13 thiols studied, three groups of thiols are distinguishable:
      (i) Group I includes cysteine and its four congeners (cysteine methyl ester,
      cysteine ethyl ester, homocysteine, cysteamine); they are subject to rapid
      oxidative decomposition and have the least anti-nitrosative activity. (ii) Group
      II consists of glutathione, penicillamine, tiopronin and mesna; they have the
      greatest effect on delaying the nitrosation reaction. (iii) Group III comprises N
      acetylcysteine, N-acetylpenicillamine, captopril, and thioglycolate; they all
      have high pK(a) for the mercapto group and show the strongest inhibitory effect
      on the rate and extent of nitrosation in the system studied.

PMID- 21168388
TI  - Hypoxia differentially regulates VEGFR1 and VEGFR2 levels and alters
      intracellular signaling and cell migration in endothelial cells.
AB  - The role of hypoxia on endothelial cell function and response to growth factors
      is unknown. Here, we tested the hypothesis that hypoxia re-programs endothelial
      function by modulating vascular endothelial growth factor receptor levels which
      in turn alter intracellular signaling and cell function. Hypoxia stimulated VEGF
      A and VEGFR1 expression but decreased VEGFR2 levels in endothelial cells. During
      hypoxia, plasma membrane VEGFR1 levels were elevated whereas VEGFR2 levels were
      depleted. One functional consequence of hypoxia is a reduction in VEGF-A
      stimulated and VEGFR2-regulated intracellular signaling including lowered
      endothelial nitric oxide synthase activation. Venous, arterial and capillary
      endothelial cells subjected to hypoxia all exhibited reduced cell migration in
      response to VEGF-A. A mechanistic explanation is that VEGFR1:VEGFR2 ratio is
      substantially increased during hypoxia to block VEGF-A-stimulated and VEGFR2
      regulated endothelial responses to maximize cell viability and recovery.

PMID- 21168389
TI  - Octaarginine-modified liposomes enhance the anti-oxidant effect of Lecithinized
      superoxide dismutase by increasing its cellular uptake.
AB  - The anti-oxidant enzyme superoxide dismutase (SOD) has the potential for use as a
      therapeutic agent in the treatment of various diseases caused by reactive oxygen
      species. However, achieving this would be difficult without a suitable delivery
      system for SOD. We previously reported that PC-SOD, in which four molecules of a
      phosphatidylcholine (PC) derivative were covalently bound to each dimer of
      recombinant human CuZnSOD, was a high affinity for the cell membrane [14]. Here,
      we show that an octaarginine (R8) modified liposome equipped with PC-SOD (R8-LP
      (PC-SOD)) enhances its anti-oxidant effect. High-density R8-modified liposomes
      can stimulate macropinocytosis and are taken up efficiently by cells as
      demonstrated in a previous study [21]. Flow cytometry analyses showed that R8-LP
      (PC-SOD) was taken up by cells more efficiently than PC-SOD. Moreover, R8-LP (PC
      SOD) liposomes were found to scavenge superoxide anions (O(2)(-)) very
      efficiently. These results suggest that the efficient cytosolic delivery of PC
      SOD by R8-modified liposomes would enhance the anti-oxidant effects of PC-SOD.

PMID- 21168390
TI  - Insulin receptor substrates form high-molecular-mass complexes that modulate
      their availability to insulin/insulin-like growth factor-I receptor tyrosine
      kinases.
AB  - Insulin receptor substrates (IRSs) are phosphorylated by activated
      insulin/insulin-like growth factor (IGF)-I receptor tyrosine kinases.
      Phosphotyrosyl IRSs are recognized by signaling molecules possessing src homology
      region 2 (SH2) domains, which mediate various insulin/IGF bioactivities. However,
      we have shown that IRSs are also associated with other proteins by a
      phosphotyrosine-independent mechanism. Here, we demonstrated that IRSs form high
      molecular-mass complexes (we named these complexes IRSomes) with various proteins
      and we elucidated their possible roles. Blue native-polyacrylamide gel
      electrophoresis of cell lysates revealed IRSome formation. Some proteins
      associated with IRSs in IRS-isoform-, cell-type-, or stimulus-specific manners.
      Results of the in vitro tyrosine phosphorylation assay indicated that tyrosine
      phosphorylation of IRS-1 by insulin receptor was decreased when IRS-1 was
      contained in IRSomes prepared from 3T3-L1 adipocytes treated with TNF-alpha.
      Also, tyrosine phosphorylation of IRS-2 by IGF-I receptor was increased when IRS
      2 was contained in IRSomes prepared from FRTL-5 thyrocytes treated with dibutyryl
      cAMP. These results demonstrated that cytokine/hormone-induced formation of
      IRSomes modulates availability of IRSs to receptor tyrosine kinases.

PMID- 21168391
TI  - Nucleoside analogs induce proteasomal down-regulation of p21 in chronic
      lymphocytic leukemia cell lines.
AB  - Nucleoside analogs (NAs) represent an important class of anticancer agents that
      induce cell death after conversion to triphosphate derivatives. One of their most
      important mechanisms of action is the activation of p53, leading to apoptosis
      through the intrinsic pathway. Classically, the activation of p53 also induces
      p21 accumulation, which leads to cell cycle arrest at the G1/S transition. In
      previous work, we observed that 2-chloro-2'-deoxyadenosine (CdA), a NA with high
      activity in lymphoid disorders, including chronic lymphocytic leukemia (CLL),
      promotes the G1/S transition in the CLL cell line EHEB at cytotoxic
      concentrations. This finding led us to investigate the p21 response to NAs in
      these cells. We show here that CdA, but also fludarabine, gemcitabine, and
      cytarabine, strongly reduced the p21 protein level in EHEB cells as well as in
      JVM-2 cells, another CLL cell line. This p21 depletion occurred despite induction
      of p53 and increase of p21 mRNA and was prevented by proteasome inhibitors.
      Increase of proteasomal degradation caused by NAs appeared to be ubiquitin
      independent. Also, NAs induced in these cells an increase of cyclin-dependent
      kinase (Cdk2) activity and a monoubiquitination of cell proliferating nuclear
      antigen (PCNA), two processes that are negatively regulated by p21. These changes
      were not observed with other p53 activators, like etoposide and nutlin-3a that
      increased the p21 protein level. In conclusion, our study reveals that NAs can
      induce an alternative pattern of cellular response in some cell models.

PMID- 21168392
TI  - The N-terminal domain of human hemokinin-1 influences functional selectivity
      property for tachykinin receptor neurokinin-1.
AB  - Human hemokinin-1 (hHK-1) is a substance P-like tachykinin peptide preferentially
      expressed in non-neuronal tissues. It is involved in multiple physiological
      functions such as inflammation, hematopoietic cells development and
      vasodilatation via the interaction with tachykinin receptor neurokinin-1 (NK1).
      To further understand the intracellular signal transduction mechanism under such
      functional multiplicity, current study was focused on the differential activation
      of Gs and Gq pathways by hHK-1 and its C-terminal fragments, which is termed as
      functional selectivity. We demonstrated these hHK-1 and related peptide fragments
      can independently activate Gs and Gq pathways, showing a relative bias toward Gq
      over Gs pathway. The T1, K3 and Q6 of hHK-1 might play roles in the activation of
      adenylate cyclase mediated by Gs, while having negligible effect on Gq mediated
      intracellular calcium release. The stepwise truncation of N-terminal amino acid
      of hHK-1 caused gradual decrease in ERK1/2 phosphorylation level and NF-kappaB
      activity. However, it had little influence on the induction of NK1 receptor
      desensitization and internalization. Taken together these data support that hHK-1
      and its C-terminal fragments are human NK1 receptor agonists with different
      functional selectivity properties and that such functional selectivity leads to
      differential activation of downstream signaling and receptor trafficking.

PMID- 21168393
TI  - Modulation of Rad51, ERCC1, and thymidine phosphorylase by emodin result in
      synergistic cytotoxic effect in combination with capecitabine.
AB  - Thymidine phosphorylase (TP) is the rate-limiting enzyme for the activation of
      capecitabine (pro-drug of fluorouracil), and as a useful predictor of tumor
      response to capecitabine-based chemotherapy. Overexpression of Rad51 and ERCC1
      induce resistance to chemotherapeutic agents. Emodin, one of the main bioactive
      anthraquinone derivatives in the roots and rhizomes of numerous plants, possesses
      potent antitumor effects. Accordingly, we aimed to explore the molecular
      mechanism of emodin enhances the capecitabine-induced cytotoxicity through
      controlling Rad51, ERCC1, and TP expression in human non-small cell lung cancer
      (NSCLC). The results show that capecitabine increases the phosphorylation of
      MKK1/2-ERK1/2 and protein levels of Rad51 and ERCC1 through enhancing the protein
      stability. Depletion of endogenous Rad51 or ERCC1 expression by specific small
      interfering RNA transfection significantly increases capecitabine-induced cell
      death and growth inhibition. Emodin enhances the capecitabine-induced cytotoxic
      effects through ERK1/2 inactivation and decreasing the Rad51 and ERCC1 protein
      levels induced by capecitabine. Enhancement of ERK1/2 signaling by constitutively
      active MKK1/2 (MKK1/2-CA) results in increasing Rad51 and ERCC1 protein levels
      and cell viability in NSCLC cell lines treated with emodin and capecitabine.
      Interestingly, emodin enhances TP mRNA and protein expression in capecitabine
      treated NSCLC cell lines, and depletion of the TP expression decreases the
      cytotoxic effects induced by capecitabine and emodin. We conclude that enhancing
      the cytotoxicity to capecitabine by emodin is mediated by down-regulation the
      expression of Rad51 and ERCC1 and up-regulation TP expression.

PMID- 21168394
TI  - Enhanced GDNF expression in dopaminergic cells of monkeys grafted with carotid
      body cell aggregates.
AB  - Striatal carotid body cell aggregates (CBCA) grafts improve parkinsonism in
      animals and patients with Parkinson's disease. As CB cells contain trophic
      factors, we investigated the long-term effect of striatal CBCA grafts on
      nigrostriatal dopaminergic cells in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP)-treated monkeys receiving unilateral (UL-grafted group, n=4) or bilateral
      (BL-grafted group, n=3) CBCA autotransplant. Two MPTP monkeys were sham-operated
      receiving only Tyrode. For histological analysis, we also included 3 MPTP
      untreated and 3 intact animals. Brain [18]F-luorodopa ((18)F-DOPA)-positron
      emission tomography (PET) scans were performed to assess dopaminergic function in
      vivo at baseline, 6 and 12months after surgery. The number of nigral dopaminergic
      cells was assessed in UL-grafted animals, and the number of dopaminergic cells
      expressing glial cell line-derived neurotrophic factor (GDNF) in all groups.
      After 1 year, animals showed a significant recovery of the parkinsonism (San
      Sebastian et al., 2007) and PET studies revealed a larger striatal (18)F-DOPA
      uptake in the CBCA-grafted striatum compared to that receiving Tyrode. No
      differences were found in the number of surviving dopaminergic cells when
      comparing both subtantia nigra of UL-grafted animals. However, both UL- and BL
      grafted animals showed a bilaterally increased number of TH-GDNF immunoreactive
      nigral neurons compared to intact and MPTP-untreated monkeys, indicating that in
      addition to the proven long-term motor benefit, CBCA autograft might exert a
      neuroprotective effect on the surviving dopaminergic cells.

PMID- 21168396
TI  - Variation in the ADH1B proximal promoter affects expression.
AB  - The primary pathway of metabolism of dietary alcohol is via its oxidation in
      liver by alcohol dehydrogenases (ADH). Differences in the ADH enzyme activity or
      levels of enzyme present could affect the risk for alcoholism. Regulatory
      variations have been shown to affect the promoter activity and thereby affect the
      risk for alcoholism. In this study the functional effects of the two SNPs
      (rs1159918 and rs1229982) in the proximal promoter region of ADH1B that were
      associated with alcoholism were explored. We examined the effects of five
      naturally occurring haplotypes on the promoter activity. We observed that a C to
      A change at rs1229982 increased promoter activity 1.4-fold.

PMID- 21168395
TI  - Infraslow EEG oscillations organize large-scale cortical-subcortical interactions
      during sleep: a combined EEG/fMRI study.
AB  - Infraslow (<0.1 Hz) oscillations of brain activity, measured by EEG and other
      methods, have become a subject of increasing interest. While their prominence
      during sleep has been established, the functional significance of these
      oscillations for sleep physiology is unknown. To clarify this role, we examined
      correlations between infraslow EEG oscillations and BOLD fMRI during the course
      of natural sleep in healthy volunteers. Infraslow EEG oscillations appear to
      organize a broad dissociation of activity in cortical and subcortical regions: in
      general, correlations between power in the infraslow EEG band and BOLD were
      positive in subcortical regions and negative in the cortex. Robust negative
      correlations were found principally in paramedian heteromodal cortices whereas
      positive correlations were seen in cerebellum, thalamus, basal ganglia, lateral
      neocortices and hippocampus. This pattern of correlations suggests a mechanism by
      which infraslow oscillations may organize sleep-dependent neuroplastic processes
      including consolidation of episodic memory.

PMID- 21168397
TI  - The possible use of hypericin to overcome drug resistance in cancer treatment.

PMID- 21168399
TI  - Meiotic maturation of vitrified immature chousingha (Tetracerus quadricornis)
      oocytes recovered postmortem.
AB  - The ability to recover and cryopreserve oocytes from postmortem ovaries of
      endangered or wildlife species holds tremendous potential for conservation using
      assisted reproductive technologies. The objective of this study was to assess the
      in vitro meiotic maturation of chousingha (four-horned antelope) oocytes
      following vitrification using open pulled straw (OPS) method. The average number
      of oocytes recovered per ovary was 65.6. The proportion of oocytes that matured
      was significantly lower in vitrified oocytes (29.4%) when compared with fresh
      oocytes (69.3%). The study provides evidence that it is possible to cryopreserve
      immature oocytes by vitrification collected from the ovaries of chousingha at
      postmortem and also demonstrates that these cryopreserved oocytes retain their
      potential to undergo in vitro meiotic maturation.

PMID- 21168400
TI  - Hypothermia protects H9c2 cardiomyocytes from H2O2 induced apoptosis.
AB  - The purpose of our study was to investigate underlying basic mechanisms of
      hypothermia-induced cardioprotection during oxidative stress in a cardiomyocyte
      cell culture model. For hypothermic treatment we cooled H9c2 cardiomyocytes to 20
      degrees C, maintained 20min at 20 degrees C during which short-term oxidative
      damage was inflicted with 2mM H(2)O(2,) followed by rewarming to 37 degrees C.
      Later on, we analyzed lactate dehydrogenase (LDH), caspase-3 cleavage, reactive
      oxygen species (ROS), mitochondrial activity, intracellular ATP production,
      cytoprotective signal molecules as well as DNA damage. Hypothermia decreased
      H(2)O(2) damage in cardiomyocytes as demonstrated in a lower LDH release, less
      caspase-3 cleavage and less M30 CytoDeath staining. After rewarming H(2)O(2)
      damaged cells demonstrated a significantly higher reduction rate of intracellular
      ROS compared to normothermic H(2)O(2) damaged cardiomyocytes(.) This was in line
      with a significantly greater mitochondrial dehydrogenase activity and higher
      intracellular ATP content in cooled and rewarmed cells. Moreover, hypothermia
      preserved cell viability by up-regulation of the anti-apoptotic protein Bcl-2 and
      a reduction of p53 phosphorylation. DNA damage, proven by PARP-1 cleavage and
      H2AX phosphorylation, was significantly reduced by hypothermia. In conclusion, we
      could demonstrate that hypothermia protects cardiomyocytes during oxidative
      stress by preventing apoptosis via inhibiting mitochondrial dysfunction and DNA
      damage.

PMID- 21168401
TI  - Sperm cryopreservation of the critically endangered olive barb (Sarpunti)
      Puntiussarana (Hamilton, 1822).
AB  - The present study focused on development of a sperm cryopreservation protocol for
      the critically endangered olive barb Puntiussarana (Hamilton, 1822) collected
      from two stocks within Bangladesh and reared in the Fisheries Field Laboratory,
      Bangladesh Agricultural University (BAU). The sperm were collected in Alsever's
      solution prepared at 296mOsmol kg(-1). Sperm were activated with distilled water
      (24mOsmol kg(-1)) to characterize motility. Maximum motility (90%) was observed
      within 15s after activation, and sperm remained motile for 35s. Sperm activation
      was evaluated in different osmolalities and motility was completely inhibited
      when osmolality of the extender was >=287mOsmol kg(-1). To evaluate
      cryoprotectant toxicity, sperm were equilibrated with 5%, 10% and 15% each of
      dimethyl sulfoxide (DMSO) and methanol. Sperm motility was noticeably reduced
      within 10min, when sperm were equilibrated with 15% DMSO, indicating acute
      toxicity to spermatozoa and therefore this concentration was excluded in further
      trials. Sperm were cryopreserved using DMSO at concentrations of 5% and 10% and
      methanol at 5%, 10% and 15%. The one-step freezing protocol (from 5 degrees C to 
      80 degrees C at 10 degrees C/min) was carried out in a computer-controlled
      freezer (FREEZE CONTROL(r) CL-3300; Australia) and 0.25-ml straws containing
      spermatozoa were stored in liquid nitrogen for 7-15days at -196 degrees C. The
      highest motility in thawed sperm 61+/-8% (mean+/-SD) was obtained with 10% DMSO.
      The fertilization and hatching rates were 70% and 37% for cryopreserved sperm,
      and 72% and 62% for fresh sperm. The protocol reported here can be useful for
      hatchery-scale production of olive barb. The use of cryopreserved sperm can
      facilitate hatchery operations, and can provide for long-term conservation of
      genetic resources to contribute in the recovery of critically endangered fish
      such as the olive barb.

PMID- 21168402
TI  - Low temperature survival in different life stages of the Iberian slug, Arion
      lusitanicus.
AB  - The slug Arion lusitanicus Mabille (Gastropoda: Pulmonata: Arionidae) is an
      invasive species which has spread to most parts of Europe. The area of origin is
      unknown, but A. lusitanicus seems to cope well with the local conditions in the
      countries to which it has migrated. It spreads rapidly, occurs often in high
      densities and has become a serious pest in most European countries. Therefore
      there is an urgent need for better knowledge of the ecophysiology of A.
      lusitanicus, such as the influence of climatic conditions, in order to develop
      prognostic models and strategies for novel pest management practises. The aim of
      our study was to investigate the influence of subzero temperatures in relation to
      winter survival. A. lusitanicus is shown to be freeze-tolerant in some life
      stages. Most juveniles and some adult slugs survived being frozen at -1.3 degrees
      C for 3days, but none of the slugs survived freezing at -3 degrees C. The eggs
      survived subzero temperatures (down to -2 degrees C) probably by supercooling.
      Juveniles and adults may also survive in a supercooled state (down to -3 degrees
      C) but are generally poor supercoolers. Therefore, the winter survival of A.
      lusitanicus depends to a high degree on migration to habitats protected from low
      winter temperatures, e.g. under plant litter, buried in the soil or in compost
      heaps.

PMID- 21168403
TI  - Versatility of EGF receptor ligand processing in insects.
AB  - Processing of EGF-family ligands is an essential step in triggering the EGF
      receptor pathway, which fulfills a diverse set of roles during development and
      tissue maintenance. We describe a mechanism of ligand processing which is unique
      to insects, and possibly to other invertebrates. This mechanism relies on ligand
      precursor trafficking from the ER by a chaperone, Star (S), and precursor
      cleavage by Rhomboids, a family of intra-membrane protease. Remarkably, the
      ability of Rhomboids to cleave S as well, endows the pathway with additional
      diversity. Rhomboid isoforms which also reside in the ER inactivate the chaperone
      before any ligand was trafficked, thus significantly reducing the level of ligand
      that will eventually be processed and secreted. ER localization also serves as a
      critical feature in trafficking the entire ligand-processing machinery to axonal
      termini, as the ER extends throughout the axon. Finally, examination of diverse
      species of insects demonstrates the evolution of chaperone cleavability,
      indicating that the primordial processing machinery could support long-range
      signaling by the ligand. Altering the intracellular localization of critical
      components of a conserved signaling cassette therefore provides an evolutionary
      mechanism for modulation of signaling levels, and diversification of the
      biological settings where the pathway functions.

PMID- 21168405
TI  - MicroRNAs in chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western
      world. Recent research, conducted primarily in basic science laboratories, has
      indicated a role for microRNAs (miRNAs) in the pathogenesis and prognosis of this
      disease. MiRNAs are small, non-coding, functional RNAs, that mediate post
      transcriptional inhibition of messenger RNAs. Because miRNA expression levels in
      CLL patients differ from that of normal patients, there may be a role for these
      novel small molecules as biomarkers in this disease.

PMID- 21168404
TI  - Cyclic AMP-dependent down regulation of ecto-nucleotide
      pyrophosphatase/phosphodiesterase 1 (NPP1) in rat C6 glioma.
AB  - In this communication, we demonstrate that an increase in intracellular cAMP by
      1) addition of dibutyrylic cAMP (dbcAMP), a membrane-permeable cAMP-analogue, or
      2) activation of the beta-adrenoceptor with (-)-isoproterenol, down regulates the
      levels of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) mRNA, NPP1
      protein and ecto-NPPase activity in rat C6 glioma cells. DbcAMP and (-)
      isoproterenol inhibit NPP1 expression in a time and dose-dependent manner. After
      48h of stimulation, 1mM dbcAMP or 5MUM (-)-isoproterenol decreases the amount of
      NPP1 protein by 75+/-3% and 81+/-1% respectively. Contrary to down regulation of
      NPP1, we observe an up regulation of glial fibrillary acidic protein (GFAP), a
      differentiation marker for astrocytic cells. Using specific inhibitors and
      activators, we have shown that Ca(2+), PKA, PI 3-K/PKB/GSK-3, Epac/Rap1/PP2A and
      MAP kinase modules are not involved in the inhibition of NPP1 gene expression.
      The transcription factor c-jun is significantly reduced while c-fos becomes up
      regulated after cAMP elevation. However an electrophoretic mobility shift assay
      with the activator protein-1 motif present in the promoter of the rat NPP1 gene
      indicates that this motif is not involved in the cAMP-dependent inhibition of
      NPP1 expression. In conclusion, these results indicate that intracellular cAMP
      levels regulate the expression of NPP1 in rat C6 glioma cells by a signalling
      pathway that is different from the GFAP signal transduction pathway.

PMID- 21168407
TI  - The plasma membrane redox system in Alzheimer's disease.

PMID- 21168406
TI  - Isolation and characterization of a population of stem-like progenitor cells from
      an atypical meningioma.
AB  - The majority of meningiomas are benign tumors associated with favorable outcomes;
      however, the less common aggressive variants with unfavorable outcomes often
      recur and may be due to subpopulations of less-differentiated cells residing
      within the tumor. These subpopulations of tumor cells have tumor-initiating
      properties and may be isolated from heterogeneous tumors when sorted or cultured
      in defined medium. We report the isolation and characterization of a population
      of tumor-initiating cells derived from an atypical meningioma. We identify a
      tumor-initiating population from an atypical meningioma, termed meningioma
      initiating cells (MICs). These MICs self-renew, differentiate, and can
      recapitulate the histological characteristics of the parental tumor when
      transplanted at 1000 cells into the flank regions of athymic nude mice.
      Immunohistochemistry reveals stem-like protein expression patterns similar to
      neural stem and progenitor cells (NSPCs) while genomic profiling verified the
      isolation of cancer cells (with defined meningioma chromosomal aberrations) from
      the bulk tumor. Microarray and pathway analysis identifies biochemical processes
      and gene networks related to aberrant cell cycle progression, particularly the
      loss of heterozygosity of tumor suppressor genes CDKN2A (p16(INK4A)), p14(ARF),
      and CDKN2B (p15(INK4B)). Flow cytometric analysis revealed the expression of CD44
      and activated leukocyte adhesion molecule (ALCAM/CD166); these may prove to be
      markers able to identify this cell type. The isolation and identification of a
      tumor-initiating cell population capable of forming meningiomas demonstrates a
      useful model for understanding meningioma development. This meningioma model may
      be used to study the cell hierarchy of meningioma tumorogenesis and provide
      increased understanding of malignant progression.

PMID- 21168408
TI  - Treatment with minocycline after disease onset alters astrocyte reactivity and
      increases microgliosis in SOD1 mutant mice.
AB  - Several reports have demonstrated that attenuation of microglial activation by
      minocycline, an antimicrobial drug with anti-inflammatory properties, delays
      disease progression in a mouse model of ALS. However, the negative results
      obtained in recent clinical trials raised some questions regarding the role of
      inflammatory response and glial cells as a therapeutic target in ALS. To
      investigate this controversy we took advantage of a mouse model for live imaging
      of neuroinflammatory responses in ALS (GFAP-luc/ SOD1(G93A) reporter mouse) and
      analyzed in real time the effects of minocycline treatment initiated at different
      stages of the disease. To our surprise, unlike neuroprotection that is conferred
      when minocycline is administered pre-symptomatically, treatment with minocycline
      initiated after the disease onset significantly altered glial responses and
      exaggerated neuroinflammation. Further analysis revealed that the late
      minocycline treatment was associated with significant induction of the end-stage
      GFAP-biophotonic signals, expression levels of connexin 43, a major protein of
      astrocytic gap junction and markers of microglial activation, such as Iba1 and
      CD68. The results of our study suggest that when administered at later stages of
      disease, once microglial cells are chronically reactive, minocycline may not have
      anti-inflammatory properties, and contrary to expectations, may alter astrocyte
      reactivity and increase microgliosis. Finally, our results further suggest the
      existence of close interactions/communication between activated microglia and
      astrocytes in late stage ALS.

PMID- 21168409
TI  - Functional consequences of mutational analysis of norovirus protease.
AB  - Norovirus protease has been subjected to an extensive mutagenesis study. Ala
      scanning mutation at 13 different positions (Trp6, Trp19, Thr27, Leu86, Leu95,
      Leu97, Met101, Gln117, Leu121, Thr134, Tyr143, Val144, and Val167) led to loss of
      function and/or stability. Considering the crystal structure of the protease, it
      was revealed that a hydroxyl group of Thr134 and an aromatic ring of Tyr143 were
      important for substrate recognition along with His157. It was notable that
      several of the residues identified were in close proximity to each other,
      suggesting their importance for the integrity and stability of the protease.

PMID- 21168410
TI  - Molecular identification of the enzyme responsible for the mitochondrial NADH
      supported ammonium-dependent hydrogen peroxide production.
AB  - A homogeneous protein with a subunit apparent molecular mass of ~50 kDa that
      catalyzes the previously described mitochondrial NADH-supported ammonium
      stimulated hydrogen peroxide production (Grivennikova, V.G., Gecchini, G. and
      Vinogradov, A.D. (2008) FEBS Lett. 583, 1287-1291) was purified from the
      mitochondrial matrix of bovine heart. Chromatography of partially purified
      protein showed that the peaks of ammonium-stimulated NADH-dependent H(2)O(2)
      production and that of NADH:lipoamide oxidoreductase activity coincided. The
      catalytic properties and mass spectrometry of the trypsin-digested protein
      revealed peptides that allowed identification of the protein as the Bos taurus
      dihydrolipoyl dehydrogenase.

PMID- 21168411
TI  - The active site protonation states of perdeuterated Toho-1 beta-lactamase
      determined by neutron diffraction support a role for Glu166 as the general base
      in acylation.
AB  - Room temperature neutron diffraction data of the fully perdeuterated Toho-1
      R274N/R276N double mutant beta-lactamase in the apo form were used to visualize
      deuterium atoms within the active site of the enzyme. This perdeuterated neutron
      structure of the Toho-1 R274N/R276N reveals the clearest picture yet of the
      ground-state active site protonation states and the complete hydrogen-bonding
      network in a beta-lactamase enzyme. The ground-state active site protonation
      states detailed in this neutron diffraction study are consistent with previous
      high-resolution X-ray studies that support the role of Glu166 as the general base
      during the acylation reaction in the class A beta-lactamase reaction pathway.

PMID- 21168412
TI  - Ontogenic characterization of gene expression in the developing neuroendocrine
      system of the chick.
AB  - The neuroendocrine system consists of five major hypothalamic-pituitary hormone
      axes that regulate several important metabolic processes, and it develops in all
      vertebrates during embryogenesis. In order to define initiation and establishment
      of these five axes, mRNA expression profiles of hypothalamic releasing and
      release-inhibiting factors, their pituitary receptors, and pituitary hormones
      were characterized during the second half of embryogenesis and first week post
      hatch in the chick. Axis initiation was defined as the age when pituitary hormone
      mRNA levels began to increase substantially, and establishment was defined as the
      age when mRNA for all components had reached maximum expression levels. The
      adrenocorticotropic axis appears established by e12, as there were no major
      increases in gene expression after that age. Hypothalamic thyrotropin-releasing
      hormone and pituitary thyroid-stimulating hormone beta-subunit increased between
      e10 and e18, indicating establishment of the thyrotropic axis during this period.
      Pituitary growth hormone substantially increased on e16, and hypothalamic growth
      hormone-releasing hormone did not increase until e20, indicating that
      somatotropic axis activity is established late in embryonic development.
      Lactotropic axis initiation is evident just prior to hatch, as pituitary
      prolactin and vasoactive intestinal peptide receptor 1 did not increase until e18
      and e20, respectively. Hypothalamic gonadotropin-releasing hormone 1 increased
      after hatch, and pituitary luteinizing hormone beta-subunit expression remained
      low until d3, indicating the gonadotropic axis is not fully functional until
      after hatching. This study is the first to characterize major hypothalamic and
      pituitary components of all five neuroendocrine axes simultaneously and
      considerably increases our understanding of neuroendocrine system establishment
      during development.

PMID- 21168413
TI  - FRET peptides reveal differential proteolytic activation in intraerythrocytic
      stages of the malaria parasites Plasmodium berghei and Plasmodium yoelii.
AB  - Malaria is still a major health problem in developing countries. It is caused by
      the protist parasite Plasmodium, in which proteases are activated during the cell
      cycle. Ca(2+) is a ubiquitous signalling ion that appears to regulate protease
      activity through changes in its intracellular concentration. Proteases are
      crucial to Plasmodium development, but the role of Ca(2+) in their activity is
      not fully understood. Here we investigated the role of Ca(2+) in protease
      modulation among rodent Plasmodium spp. Using fluorescence resonance energy
      transfer (FRET) peptides, we verified protease activity elicited by Ca(2+) from
      the endoplasmatic reticulum (ER) after stimulation with thapsigargin (a
      sarco/endoplasmatic reticulum Ca(2+)-ATPase (SERCA) inhibitor) and from acidic
      compartments by stimulation with nigericin (a K(+)/H(+) exchanger) or monensin (a
      Na(+)/H(+) exchanger). Intracellular (BAPTA/AM) and extracellular (EGTA) Ca(2+)
      chelators were used to investigate the role played by Ca(2+) in protease
      activation. In Plasmodium berghei both EGTA and BAPTA blocked protease
      activation, whilst in Plasmodium yoelii these compounds caused protease
      activation. The effects of protease inhibitors on thapsigargin-induced
      proteolysis also differed between the species. Pepstatin A and
      phenylmethylsulphonyl fluoride (PMSF) increased thapsigargin-induced proteolysis
      in P. berghei but decreased it in P. yoelii. Conversely, E64 reduced proteolysis
      in P. berghei but stimulated it in P. yoelii. The data point out key differences
      in proteolytic responses to Ca(2+) between species of Plasmodium.

PMID- 21168414
TI  - The roles of temperature and light in black band disease (BBD) progression on
      corals of the genus Diploria in Bermuda.
AB  - On Bermuda reefs the brain coral Diploria labyrinthiformis is rarely documented
      with black band disease (BBD), while BBD-affected colonies of Diploria strigosa
      are common. D. labyrinthiformis on these reefs may be more resistant to BBD or
      less affected by prevailing environmental conditions that potentially diminish
      host defenses. To determine whether light and/or temperature influence BBD
      differently on these two species, infection experiments were conducted under the
      following experimental treatments: (1) 26  degrees C, ambient light; (2) 30 
      degrees C, ambient light; (3) 30  degrees C, low light; and (4) 30  degrees C,
      high light. A digital photograph of the affected area of each coral was taken
      each day for 7 days and analyzed with ImageJ image processing software. The final
      affected area was not significantly different between species in any of the four
      treatments. BBD lesions were smaller on both species infected under ambient light
      at 26  degrees C versus 30  degrees C. Low light at 30  degrees C significantly
      reduced the lesion size on both species when compared to colonies infected at the
      same temperature under ambient light. Under high light at 30  degrees C, BBD
      lesions were larger on colonies of D. strigosa and smaller on colonies of D.
      labyrinthiformis when compared to colonies infected under ambient light at the
      same temperature. The responses of both species suggests that BBD progression on
      both D. strigosa and D. labyrinthiformis is similarly influenced by a combination
      of light and temperature and that other factors present before infections become
      established likely contribute to the difference in BBD prevalence in Bermuda.

PMID- 21168415
TI  - Variability of shell repair in the Manila clam Ruditapes philippinarum affected
      by the Brown Ring Disease: a microstructural and biochemical study.
AB  - For more than two decades, the Manila clam Ruditapes philippinarum has been
      regularly affected by Brown Ring Disease (BRD), an epizootic event caused by the
      bacterium Vibrio tapetis and characterized by the development of a brown deposit
      on the inner face of valves. Although BRD infection is often lethal, some clams
      recover by mineralizing a new repair shell layer, which covers the brown deposit
      and fully isolates it from living tissues. In order to understand this specific
      shell repair process, the microstructures of repaired zones were compared to
      those of shells unaffected by BRD. In addition, the organic matrix associated
      with unaffected shells and to repair patches were extracted and compared by
      biochemical and immunological techniques. Our results show that the repaired
      zones exhibit microstructures that resemble the so-called homogeneous
      microstructure of the internal layer, with some marked differences, like the
      development of crossed-acicular crystals, which form chevron-like patterns. In
      the three tested batches of repaired layers, the matrices exhibit certain
      heterogeneity, i.e., they are partially to widely different from the ones of
      shells unaffected by BRD, as illustrated by SDS-PAGE and by serological
      comparisons. Our results strongly suggest a modification of the secretory regime
      of calcifying mantle cells during the shell repair process. Polyclonal
      antibodies, which were developed against specific protein fractions of the shell,
      represent relevant tools for localizing by immunohistology the cells responsible
      for the repair.

PMID- 21168416
TI  - Crystal structure of Escherichia coli BamB, a lipoprotein component of the beta
      barrel assembly machinery complex.
AB  - In Gram-negative bacteria, the BAM (beta-barrel assembly machinery) complex
      catalyzes the essential process of assembling outer membrane proteins. The BAM
      complex in Escherichia coli consists of five proteins: one beta-barrel membrane
      protein, BamA, and four lipoproteins, BamB, BamC, BamD, and BamE. Despite their
      role in outer membrane protein biogenesis, there is currently a lack of
      functional and structural information on the lipoprotein components of the BAM
      complex. Here, we report the first crystal structure of BamB, the largest and
      most functionally characterized lipoprotein component of the BAM complex. The
      crystal structure shows that BamB has an eight-bladed beta-propeller structure,
      with four beta-strands making up each blade. Mapping onto the structure the
      residues previously shown to be important for BamA interaction reveals that these
      residues, despite being far apart in the amino acid sequence, are localized to
      form a continuous solvent-exposed surface on one side of the beta-propeller.
      Found on the same side of the beta-propeller is a cluster of residues conserved
      among BamB homologs. Interestingly, our structural comparison study suggests that
      other proteins with a BamB-like fold often participate in protein or ligand
      binding, and that the binding interface on these proteins is located on the
      surface that is topologically equivalent to where the conserved residues and the
      residues that are important for BamA interaction are found on BamB. Our
      structural and bioinformatic analyses, together with previous biochemical data,
      provide clues to where the BamA and possibly a substrate interaction interface
      may be located on BamB.

PMID- 21168418
TI  - Crystal structures exploring the origins of the broader specificity of
      escherichia coli heat-labile enterotoxin compared to cholera toxin.
AB  - Cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT) are
      structurally and functionally related and share the same primary receptor, the
      GM1 ganglioside. Despite their extensive similarities, these two toxins exhibit
      distinct ligand specificities, with LT being more promiscuous than CT. Here, we
      have attempted to rationalize the broader binding specificity of LT and the
      subtle differences between the binding characteristics of LTs from human and
      porcine origins (mediated by their B subunit pentamers, hLTB and pLTB,
      respectively). The analysis is based on two crystal structures of pLTB in
      complexes with the pentasaccharide of its primary ligand, GM1, and with
      neolactotetraose, the carbohydrate determinant of a typical secondary ligand of
      LTs, respectively. Important molecular determinants underlying the different
      binding specificities of LTB and CTB are found to be contributed by Ser95, Tyr18
      and Thr4 (or Ser4 of hLTB), which together prestabilize the binding site by
      positioning Lys91, Glu51 and the adjacent loop region (50-61) containing Ile58
      for ligand binding. Glu7 and Ala1 may also play an important role. Many of these
      residues are closely connected with a recently identified second binding site,
      and there appears to be cross-talk between the two sites. Binding to N
      acetyllactosamine-terminated receptors is further augmented by Arg13 (present in
      pLT and some hLT variants), as previously predicted.

PMID- 21168419
TI  - Crystal structures of the bacterial solute receptor AcbH displaying an exclusive
      substrate preference for beta-D-galactopyranose.
AB  - Solute receptors (binding proteins) are indispensable components of canonical ATP
      binding cassette importers in prokaryotes. Here, we report on the
      characterization and crystal structures in the closed and open conformations of
      AcbH, the solute receptor of the putative carbohydrate transporter AcbFG which is
      encoded in the acarbose (acarviosyl-1,4-maltose) biosynthetic gene cluster from
      Actinoplanes sp. SE50/110. Binding assays identified AcbH as a high-affinity
      monosaccharide-binding protein with a dissociation constant (K(d)) for beta-d
      galactopyranose of 9.8+/-1.0 nM. Neither galactose-containing di- and
      trisaccharides, such as lactose and raffinose, nor monosaccharides including d
      galacturonic acid, l-arabinose, d-xylose and l-rhamnose competed with
      [(1)(4)C]galactose for binding to AcbH. Moreover, AcbH does not bind d-glucose,
      which is a common property of all but one d-galactose-binding proteins
      characterized to date. Strikingly, determination of the X-ray structure revealed
      that AcbH is structurally homologous to maltose-binding proteins rather than to
      glucose-binding proteins. Two helices are inserted in the substrate-binding
      pocket, which reduces the cavity size and allows the exclusive binding of
      monosaccharides, specifically beta-d-galactopyranose, in the (4)C(1)
      conformation. Site-directed mutagenesis of three residues from the binding pocket
      (Arg82, Asp361 and Arg362) that interact with the axially oriented O4-H hydroxyl
      of the bound galactopyranose and subsequent functional analysis indicated that
      these residues are crucial for galactose binding. To our knowledge, this is the
      first report of the tertiary structure of a solute receptor with exclusive
      affinity for beta-d-galactopyranose. The putative role of a galactose import
      system in the context of acarbose metabolism in Actinoplanes sp. is discussed.

PMID- 21168417
TI  - The human mitochondrial tRNAMet: structure/function relationship of a unique
      modification in the decoding of unconventional codons.
AB  - Human mitochondrial mRNAs utilize the universal AUG and the unconventional
      isoleucine AUA codons for methionine. In contrast to translation in the
      cytoplasm, human mitochondria use one tRNA, hmtRNA(Met)(CAU), to read AUG and AUA
      codons at both the peptidyl- (P-), and aminoacyl- (A-) sites of the ribosome. The
      hmtRNA(Met)(CAU) has a unique post-transcriptional modification, 5
      formylcytidine, at the wobble position 34 (f(5)C(34)), and a cytidine
      substituting for the invariant uridine at position 33 of the canonical U-turn in
      tRNAs. The structure of the tRNA anticodon stem and loop domain
      (hmtASL(Met)(CAU)), determined by NMR restrained molecular modeling, revealed how
      the f(5)C(34) modification facilitates the decoding of AUA at the P- and the A
      sites. The f(5)C(34) defined a reduced conformational space for the nucleoside,
      in what appears to have restricted the conformational dynamics of the anticodon
      bases of the modified hmtASL(Met)(CAU). The hmtASL(Met)(CAU) exhibited a C-turn
      conformation that has some characteristics of the U-turn motif. Codon binding
      studies with both Escherichia coli and bovine mitochondrial ribosomes revealed
      that the f(5)C(34) facilitates AUA binding in the A-site and suggested that the
      modification favorably alters the ASL binding kinetics. Mitochondrial translation
      by many organisms, including humans, sometimes initiates with the universal
      isoleucine codons AUU and AUC. The f(5)C(34) enabled P-site codon binding to
      these normally isoleucine codons. Thus, the physicochemical properties of this
      one modification, f(5)C(34), expand codon recognition from the traditional AUG to
      the non-traditional, synonymous codons AUU and AUC as well as AUA, in the
      reassignment of universal codons in the mitochondria.

PMID- 21168420
TI  - Some remarks on protein attribute prediction and pseudo amino acid composition.
AB  - With the accomplishment of human genome sequencing, the number of sequence-known
      proteins has increased explosively. In contrast, the pace is much slower in
      determining their biological attributes. As a consequence, the gap between
      sequence-known proteins and attribute-known proteins has become increasingly
      large. The unbalanced situation, which has critically limited our ability to
      timely utilize the newly discovered proteins for basic research and drug
      development, has called for developing computational methods or high-throughput
      automated tools for fast and reliably identifying various attributes of
      uncharacterized proteins based on their sequence information alone. Actually,
      during the last two decades or so, many methods in this regard have been
      established in hope to bridge such a gap. In the course of developing these
      methods, the following things were often needed to consider: (1) benchmark
      dataset construction, (2) protein sample formulation, (3) operating algorithm (or
      engine), (4) anticipated accuracy, and (5) web-server establishment. In this
      review, we are to discuss each of the five procedures, with a special focus on
      the introduction of pseudo amino acid composition (PseAAC), its different modes
      and applications as well as its recent development, particularly in how to use
      the general formulation of PseAAC to reflect the core and essential features that
      are deeply hidden in complicated protein sequences.

PMID- 21168421
TI  - The effect of time delays on Caribbean coral-algal interactions.
AB  - The analysis of ecological models often focuses on their asymptotic behavior, but
      there is increasing recognition that it is important to understand the role of
      transient behavior. By introducing a time delay into a model of coral-algal
      interactions in Caribbean coral reefs that exhibits alternative stable states (a
      favorable coral rich state and a degraded coral-depleted state), we demonstrate
      the criticality of understanding the basins of attraction for stable equilibria
      in addition to the systems' asymptotic behavior. Specifically, we show that
      although the introduction of a time delay into the model does not change the
      asymptotic stability of the stable equilibria, there are significant changes to
      their basins of attraction. An understanding of these effects is necessary when
      determining appropriate reef management options. We then demonstrate that this is
      a general phenomenon by considering similar behavior underlying the changes in
      the basins of attraction in a simple Lotka-Volterra model of competition.

PMID- 21168422
TI  - Estimation of the incubation period of influenza A (H1N1-2009) among imported
      cases: addressing censoring using outbreak data at the origin of importation.
AB  - Empirical estimates of the incubation period of influenza A (H1N1-2009) have been
      limited. We estimated the incubation period among confirmed imported cases who
      traveled to Japan from Hawaii during the early phase of the 2009 pandemic (n=72).
      We addressed censoring and employed an infection-age structured argument to
      explicitly model the daily frequency of illness onset after departure. We assumed
      uniform and exponential distributions for the frequency of exposure in Hawaii,
      and the hazard rate of infection for the latter assumption was retrieved, in
      Hawaii, from local outbreak data. The maximum likelihood estimates of the median
      incubation period range from 1.43 to 1.64 days according to different modeling
      assumptions, consistent with a published estimate based on a New York school
      outbreak. The likelihood values of the different modeling assumptions do not
      differ greatly from each other, although models with the exponential assumption
      yield slightly shorter incubation periods than those with the uniform exposure
      assumption. Differences between our proposed approach and a published method for
      doubly interval-censored analysis highlight the importance of accounting for the
      dependence of the frequency of exposure on the survival function of incubating
      individuals among imported cases. A truncation of the density function of the
      incubation period due to an absence of illness onset during the exposure period
      also needs to be considered. When the data generating process is similar to that
      among imported cases, and when the incubation period is close to or shorter than
      the length of exposure, accounting for these aspects is critical for long
      exposure times.

PMID- 21168423
TI  - A two-compartment mechanochemical model of the roles of transforming growth
      factor beta and tissue tension in dermal wound healing.
AB  - The repair of dermal tissue is a complex process of interconnected phenomena,
      where cellular, chemical and mechanical aspects all play a role, both in an
      autocrine and in a paracrine fashion. Recent experimental results have shown that
      transforming growth factor -beta (TGFbeta) and tissue mechanics play roles in
      regulating cell proliferation, differentiation and the production of
      extracellular materials. We have developed a 1D mathematical model that considers
      the interaction between the cellular, chemical and mechanical phenomena, allowing
      the combination of TGFbeta and tissue stress to inform the activation of
      fibroblasts to myofibroblasts. Additionally, our model incorporates the observed
      feature of residual stress by considering the changing zero-stress state in the
      formulation for effective strain. Using this model, we predict that the continued
      presence of TGFbeta in dermal wounds will produce contractures due to the
      persistence of myofibroblasts; in contrast, early elimination of TGFbeta
      significantly reduces the myofibroblast numbers resulting in an increase in wound
      size. Similar results were obtained by varying the rate at which fibroblasts
      differentiate to myofibroblasts and by changing the myofibroblast apoptotic rate.
      Taken together, the implication is that elevated levels of myofibroblasts is the
      key factor behind wounds healing with excessive contraction, suggesting that
      clinical strategies which aim to reduce the myofibroblast density may reduce the
      appearance of contractures.

PMID- 21168424
TI  - Magnetic stimulation of the dorsolateral prefrontal cortex dissociates fragile
      visual short-term memory from visual working memory.
AB  - To guide our behavior in successful ways, we often need to rely on information
      that is no longer in view, but maintained in visual short-term memory (VSTM).
      While VSTM is usually broken down into iconic memory (brief and high-capacity
      store) and visual working memory (sustained, yet limited-capacity store), recent
      studies have suggested the existence of an additional and intermediate form of
      VSTM that depends on activity in extrastriate cortex. In previous work, we have
      shown that this fragile form of VSTM can be dissociated from iconic memory. In
      the present study, we provide evidence that fragile VSTM is different from visual
      working memory as magnetic stimulation of the right dorsolateral prefrontal
      cortex (DLPFC) disrupts visual working memory, while leaving fragile VSTM intact.
      In addition, we observed that people with high DLPFC activity had superior
      working memory capacity compared to people with low DLPFC activity, and only
      people with high DLPFC activity really showed a reduction in working memory
      capacity in response to magnetic stimulation. Altogether, this study shows that
      VSTM consists of three stages that have clearly different characteristics and
      rely on different neural structures. On the methodological side, we show that it
      is possible to predict individual susceptibility to magnetic stimulation based on
      functional MRI activity.

PMID- 21168426
TI  - Visual action control does not rely on strangers--effects of pictorial cues under
      monocular and binocular vision.
AB  - Fast goal-directed actions are supposed to be controlled almost exclusively by
      bottom-up visual control. This mode of processing has been identified with the so
      called dorsal visual stream. It is generally accepted that object recognition,
      mediated by the ventral stream, must be important for deciding what action to
      execute depending on the specific object to be grasped and the particular
      purpose. In contrast, the kinematic parameters of the actual movement itself are
      supposed to be unaffected by recognition processes. This view was recently
      challenged by the demonstration of a significant impact of object familiarity on
      grasping kinematics under binocular visual control (McIntosh & Lashley, 2008).
      This effect was observed for very well known everyday objects. However, it
      remained unclear whether the effect was really due to long-term, everyday
      familiarity of the target objects or whether it was simply mediated by short-term
      learning during the experiment. Therefore, we examined whether the same effect
      could also be found with objects that were geometrically identical to the ones
      used by McIntosh and Lashley (2008) and could be distinguished by a pictorial cue
      but were not associated with long-term, everyday experience. We only found an
      effect of familiarity under monocular but not under binocular control. Our
      observation suggests that indeed familiarity exerts an effect on movements under
      binocular control only if explicit knowledge about the objects is very stable and
      salient, e.g. after long-term experience.

PMID- 21168425
TI  - Spatial and numerical abilities without a complete natural language.
AB  - We studied the cognitive abilities of a 13-year-old deaf child, deprived of most
      linguistic input from late infancy, in a battery of tests designed to reveal the
      nature of numerical and geometrical abilities in the absence of a full linguistic
      system. Tests revealed widespread proficiency in basic symbolic and non-symbolic
      numerical computations involving the use of both exact and approximate numbers.
      Tests of spatial and geometrical abilities revealed an interesting patchwork of
      age-typical strengths and localized deficits. In particular, the child performed
      extremely well on navigation tasks involving geometrical or landmark information
      presented in isolation, but very poorly on otherwise similar tasks that required
      the combination of the two types of spatial information. Tests of number- and
      space-specific language revealed proficiency in the use of number words and
      deficits in the use of spatial terms. This case suggests that a full linguistic
      system is not necessary to reap the benefits of linguistic vocabulary on basic
      numerical tasks. Furthermore, it suggests that language plays an important role
      in the combination of mental representations of space.

PMID- 21168427
TI  - Self-face enhances processing of immediately preceding invisible faces.
AB  - The self-face is thought to be an especially salient stimulus. Behavioral
      evidence suggests that self-face processing advantage is associated with enhanced
      processing of temporally adjacent subliminal stimuli. However, the neural basis
      of this self-related processing modulation has not been investigated. We studied
      self-face induced signal amplification through masked priming and repetition
      suppression (fMRI adaptation). Subjects performed a gender-categorization task on
      self- and non-self target faces preceded by subliminal (17 ms) prime faces. The
      relationship between prime and target was varied between task-incongruent (when
      prime and target belonged to a different gender) and task-congruent (when prime
      and target belonged to the same gender) pairs. We found that, in the presence of
      the visible self-face (but not of other non-self faces), a bilateral fronto
      parietal network exhibited repetition suppression to subliminal prime faces
      belonging to the same gender (task-congruent) as the target, consistent with the
      notion that, in the presence of the self-face, subliminal stimuli access high
      level processing systems. These results are in agreement with the notion of self
      specific top-down amplification of subliminal task-relevant information, and
      suggest that the self-face, through its high salience, is particularly
      efficacious in focusing attention.

PMID- 21168428
TI  - HPA axis dampening by limited sucrose intake: reward frequency vs. caloric
      consumption.
AB  - Individuals often cope with stress by consuming calorically-dense, highly
      palatable 'comfort' foods. The present work explores the stress-relieving
      properties of palatable foods in a rat model of limited sucrose intake. In this
      model, adult male rats with free access to chow and water are given additional
      access to a small amount of sucrose drink (or water as a control). A history of
      such limited sucrose intake reduces the collective (HPA axis, sympathetic, and
      behavioral-anxiety) stress response. Moreover, the stress-dampening by sucrose
      appears to be mediated primarily by its rewarding properties, since beneficial
      effects are reproduced by the noncaloric sweetener saccharin but not oral
      intragastric gavage of sucrose. The present work uses an alternate strategy to
      address the hypothesis that the rewarding properties of sucrose mediate its
      stress-dampening. This work varies the duration, frequency, and/or volume of
      sucrose and assesses the ability to attenuate HPA axis stress responses. The data
      indicate that HPA-dampening is optimal with a greater duration and/or frequency
      of sucrose, whereas increasing the volume of sucrose consumed is without effect.
      This finding suggests that the primary factor mediating stress-dampening is the
      number/rate of reward (i.e., sucrose) exposures, rather than the total sucrose
      calories consumed. Collectively, these data support the hypothesis that stress
      relief by limited palatable food intake is mediated primarily by its
      hedonic/rewarding properties. Moreover, the results support the contention that
      naturally rewarding behaviors are a physiological means to produce stress relief.

PMID- 21168429
TI  - The anorectic response to growth hormone in obese rats is associated with an
      increased rate of lipid oxidation and decreased hypothalamic galanin.
AB  - The aim of this study was to demonstrate differential effects of growth hormone
      (GH) on food intake in lean and obese rats and to investigate whether an
      anticipated anorectic response in obese rats might be associated with increased
      lipid oxidation and altered hypothalamic neuropeptide levels. GH (4 mg/kg/day)
      was administered during 5-21 days to non-obese and obese rats. Whereas GH
      stimulated food intake in the non-obese rats, the obese animals responded with a
      significantly (p<0.05) suppressed food intake for 4-5 days. On day 4, the obese
      rats injected with GH and those injected with vehicle consumed 9.2 +/- 0.66 g and
      12.7 +/- 1.05 g, respectively. The suppression of food intake was associated with
      significantly (p<0.05) increased lipid oxidation. A similar, but statistically
      not verified, trend was seen in pair-fed rats not exposed to GH. However, while
      these animals appeared to economize their energy expenditure, the GH-exposed
      animals did not, thus creating a significant (p<0.05) difference between these
      two groups. The increased lipid oxidation and energy expenditure observed in the
      rats exposed to GH were associated with significantly (p<0.05) decreased levels
      of hypothalamic galanin (111 +/- 33.2 pmol/g vs. those of the pair-fed controls:
      228.5 +/- 49.4 pmol/g). This difference was, however, not sustained. Thus, on day
      21 both hypothalamic galanin and the food intake in the GH group were back to
      normal. Hypothalamic NPY remained unchanged by GH at all times. In conclusion,
      the present study suggests that increased lipid oxidation and decreased
      hypothalamic galanin are components in the mechanism by which GH inhibits food
      intake in an obese phenotype.

PMID- 21168430
TI  - Dehydroepiandrosterone fatty acyl esters in high density lipoprotein: interaction
      with human vascular endothelial cells and vascular responses ex vivo.
AB  - Dehydroepiandrosterone (DHEA) fatty acyl esters once incorporated in high density
      lipoprotein (HDL) induce a stronger vasodilatory response in rat mesenteric
      arteries ex vivo compared to native HDL. We studied the role of HDL receptor,
      scavenger receptor class B, type 1 (SR-B1), as well as estrogen and androgen
      receptors in the vasodilatory response of HDL-associated DHEA fatty acyl esters.
      Using cultured human vascular endothelial cells (HUVEC), we investigated the
      possible internalization and cellular response of HDL-associated DHEA esters. We
      prepared DHEA ester-enriched HDL by incubating human plasma in the presence of
      DHEA. After isolation and purification, HDL was added in cumulative doses to
      arterial rings precontracted with noradrenaline. Inhibition of the function of SR
      B1 almost completely abolished maximal vasorelaxation by DHEA-enriched HDL while
      estrogen or androgen receptor blockage had no significant effect. When HUVECs
      were incubated in the presence of [3H]DHEA ester-enriched HDL, the amount of
      intracellular [3H]-radioactivity increased steadily during 24 h. Blocking of SR
      B1 reduced this uptake by a mean of 30%. The proportion of unesterified [3H]DHEA,
      as analyzed by thin-layer chromatography, increased intracellularly and in the
      cell culture media after several hours of incubation of the cells in the presence
      of [3H]DHEA ester-enriched HDL. This indicated slow hydrolysis of DHEA fatty acyl
      esters and subsequent excretion of unesterified DHEA by the cells. In conclusion,
      DHEA-enriched HDL induced vasorelaxation via the SR-B1-facilitated pathway.
      However, this vasodilation is not likely to be attributed to rapid hydrolysis of
      HDL-associated DHEA esters by the vascular endothelium.

PMID- 21168431
TI  - Inhibition of the thioredoxin system in the brain and liver of zebra-seabreams
      exposed to waterborne methylmercury.
AB  - Mercury compounds were recently found to interact in vitro with the thioredoxin
      system, inhibiting both Thioredoxin (Trx) and Thioredoxin reductase (TrxR). In
      order to evaluate if Trx and TrxR are affected in vivo by methylmercury (MeHg),
      we exposed juvenile zebra-seabreams to different concentrations of this toxicant
      in water for 28days followed by a 14-day depuration period. Methylmercury
      accumulated to a larger extent in the kidney and liver of fishes, but decreased
      significantly during the depuration. During the exposure, MeHg percentage in the
      liver reached levels above 90% of total mercury (HgT) decreasing to 60% of HgT by
      the end of the depuration period. In the kidney, MeHg accounted for 50-70% of
      HgT. In the brain and muscle, mercury accumulated throughout the exposure with
      all mercury being MeHg. The total mercury kept increasing in these organs during
      the depuration period. However, in the brain, this increase in HgT was
      accompanied by a decrease in the MeHg percentage (~10%). In the liver, both Trx
      and TrxR activities were significantly reduced (TrxR--40%; Trx--70%) by the end
      of the exposure, but recovered to control levels (100%) during the depuration. In
      the brain, both enzymes where inhibited during the depuration period (TrxR--75%;
      Trx--70%) when some production of inorganic mercury was detected. Activity of
      glutathione reductase showed increased levels when TrxR activity was low,
      suggesting complementarity between both systems. These results indicate that in
      vivo the thioredoxin system is a toxicological target for MeHg with TrxR being
      particularly affected.

PMID- 21168432
TI  - Sulfation of chlorotyrosine and nitrotyrosine by human lung endothelial and
      epithelial cells: role of the human SULT1A3.
AB  - During inflammation, potent reactive oxidants formed may cause chlorination and
      nitration of both free and protein-bound tyrosine. In addition to serving as
      biomarkers of inflammation-mediated oxidative stress, elevated levels of
      chlorotyrosine and nitrotyrosine have been linked to the pathogenesis of lung and
      vascular disorders. The current study was designed to investigate whether the
      lung cells are equipped with mechanisms for counteracting these tyrosine
      derivatives. By metabolic labeling, chlorotyrosine O-[35S]sulfate and
      nitrotyrosine O-[35S]sulfate were found to be generated and released into the
      labeling media of human lung endothelial and epithelial cells labeled with
      [35S]sulfate in the presence of added chlorotyrosine and nitrotyrosine. Enzymatic
      assays using the eleven known human cytosolic sulfotransferases (SULTs) revealed
      SULT1A3 as the enzyme responsible for catalyzing the sulfation of chlorotyrosine
      and nitrotyrosine. Reverse transcription-polymerase chain reaction (RT-PCR)
      analysis demonstrated the expression of SULT1A3 in the lung endothelial and
      epithelial cells used in this study. Kinetic constants of the sulfation of
      chlorotyrosine and nitrotyrosine by SULT1A3 were determined. Collectively, these
      results suggest that sulfation by SULT1A3 in lung endothelial and epithelial
      cells may play a role in the inactivation and/or disposal of excess
      chlorotyrosine and nitrotyrosine generated during inflammation.

PMID- 21168433
TI  - Periconceptional nutrition and the early programming of a life of obesity or
      adversity.
AB  - Women entering pregnancy with a high body weight and fat mass have babies at
      increased risk of becoming overweight or obese in childhood and later life. It is
      not known, whether exposure to a high level of maternal nutrition before
      pregnancy and exposure to a high transplacental nutrient supply in later
      pregnancy act through similar mechanisms to program later obesity. Using the
      pregnant sheep we have shown that maternal overnutrition in late pregnancy
      results in an upregulation of PPARgamma activated genes in fetal visceral fat and
      a subsequent increase in the mass of subcutaneous fat in the postnatal lamb.
      Exposure to maternal overnutrition during the periconceptional period alone,
      however, results in an increase in total body fat mass in female lambs only with
      a dominant effect on visceral fat depots. Thus the early programming of later
      obesity may result from 'two hits', the first occurring as a result of maternal
      overnutrition during the periconceptional period and the second occurring as a
      result of increased fetal nutrition in late pregnancy. Whilst a short period of
      dietary restriction during the periconceptional period reverses the impact of
      periconceptional overnutrition on the programming of obesity, it also results in
      an increased lamb adrenal weight and cortisol stress response, together with
      changes in the epigenetic state of the insulin like growth factor 2 (IGF2) gene
      in the adrenal. Thus, not all of the effects of dietary restriction in overweight
      or obese mother in the periconceptional period may be beneficial in the longer
      term.

PMID- 21168434
TI  - Processing of fish Ig heavy chain transcripts: diverse splicing patterns and
      unusual nonsense mediated decay.
AB  - While the diversification of the antigen-binding sites is realized by genomic VDJ
      rearrangements during B cell differentiation, different forms of immunoglobulin
      (Ig) heavy (H) chains can be produced through multiple splicing pathways. In most
      vertebrates, the secreted (S) and membrane (Mb) forms of IgM chain are created by
      alternative splicing through usage of a cryptic splice site in CMU4 allowing the
      junction to the TM exon. The processing pattern for IgMU is different in
      teleosts, which generally use the CMU3 donor site instead. In ancient fish
      lineages, multiple unusual splicing patterns were found for Ig H chain, involving
      donor sites that do not always follow the classical consensus. The production of
      IgD versus IgM H chains seems to be generally realized by alternative splicing in
      all vertebrates, but typical teleost IgD H chains are chimeric and contains a
      CMU1 domain. Together, these observations raise questions on how different fish
      regulate RNA splicing and if their splicing machinery is especially complex. A
      preliminary scan of the zebrafish and stickleback genomes provides evidence that
      gene orthologs to the mammalian main splice factors are highly conserved as
      single copy genes, while the snRNPs U repertoire may be different and may explain
      other particular features of RNA processing in fish.

PMID- 21168435
TI  - Mode of bacterial pathogenesis determines phenotype in elt-2 and elt-7 RNAi
      Caenorhabditis elegans.
AB  - Caenorhabditis elegans has become a useful model for studying innate immunity.
      ELT-2, which is homologous to human GATA-4, -5 and -6, is considered the primary
      GATA transcription factor controlling intestinal immunity in C. elegans. In this
      study, we characterize the timeline of intestinal distension in nematodes where
      ELT-2 and another intestinal GATA transcription factor, ELT-7, are abrogated by
      RNAi using two different models: colonization and toxin-based infections by
      Pseudomonas aeruginosa. We show that both ELT-2 and ELT-7 are important for
      survival of C. elegans exposed to P. aeruginosa. Intestinal distension is
      accelerated in elt-2 RNAi nematodes, and is observed in colonization but not
      toxin-based Pseudomonas infection. Upon onset of intestinal distension, nematodes
      die within 24 h, regardless of experimental treatment. These data provide new
      insight into the role of ELT-2 and ELT-7 in protecting C. elegans against P.
      aeruginosa infection.

PMID- 21168436
TI  - Brain organization and the roots of anticipation in Drosophila olfactory
      conditioning.
AB  - Defining learning at the molecular and physiological level has been one of the
      greatest challenges in biology. Recent research suggests that by studying fruit
      fly (Drosophila melanogaster) brain organization we can now begin to unravel some
      of these mysteries. The fruit fly brain is organized into executive centers that
      regulate anatomically separate behavioral systems. The mushroom body is an
      example of an executive center which is modified by olfactory conditioning.
      During this simple form of learning, an odor is paired with either food or shock.
      Either experience alters distinguishable specific circuitry within the mushroom
      body. Results suggest that after conditioning an odor to food, the mushroom body
      will activate a feeding system via a subset of its circuitry. After conditioning
      an odor to shock, the mushroom body will instead activate an avoidance system
      with other subsets of mushroom body neurons. The results of these experiments
      demonstrate a mechanism for flies to display anticipation of their environment
      after olfactory conditioning has occurred. However, these results fail to provide
      evidence for reinforcement, a consequence of action, as part of this mechanism.
      Instead, specific subsets of dopaminergic and octopaminergic neurons provide a
      simple pairing signal, in contrast to a reinforcement signal, which allows for
      prediction of the environment after experience. This view has implications for
      models of conditioning.

PMID- 21168437
TI  - Why do we yawn? The importance of evidence for specific yawn-induced effects.
AB  - Gallup (this issue) believes that our recent review on the function of yawning
      (Guggisberg et al., 2010) is unbalanced and that it ignores evidence for his
      thermoregulation hypothesis. Here we address these criticisms and show them to be
      untenable. While we never claimed that the social hypothesis of yawning has
      "definite experimental support", we emphasize the importance of experimental
      evidence for specific effects of yawns when considering why we yawn. The only
      specific effect of yawning that could be demonstrated so far is its
      contagiousness in humans, some non-human primates, and possibly dogs, whereas all
      studies investigating physiological consequences of yawns were unable to observe
      specific yawn-induced effects in the individual of any species. The argument that
      from an evolutionary perspective, yawns must have a "primitive" physiological
      function arises from imprecise reasoning.

PMID- 21168438
TI  - Poly-substance use and related harms: a systematic review of harm reduction
      strategies implemented in recreational settings.
AB  - The growing trends of poly-substance use and associated health and public
      concerns have been reported in various studies with particular focus on young
      adults patronising popular recreational settings. Harm reduction interventions
      targeting this population have been reported for a number of settings, however
      only limited data is available on the current strategies employed. A systematic
      review of peer-reviewed journals was conducted to determine interventions
      published since 1998 which targeted 17-24 year olds within recreational settings:
      defined as clubs, pubs, discos, festivals or raves. The identified studies were
      examined for similarities in design, implementation and outcome measures. The
      findings and their limitations are discussed alongside implications for future
      research needed to fill a void in the current knowledge base.

PMID- 21168439
TI  - Neuroanatomy of vulnerability to psychosis: a voxel-based meta-analysis.
AB  - BACKGROUND: Individual structural imaging studies in the pre-psychotic phases
      deliver contrasting findings and are unable to definitively characterize the
      neuroanatomical correlates of an increased liability to psychosis and to predict
      transition to psychosis. METHOD: Ninenteen voxel-based morphometry (VBM) studies
      of subjects at enhanced risk for psychosis and healthy controls were included in
      an activation likelihood estimation (ALE) meta-analysis. RESULTS: The overall
      sample consisted of 701 controls and 896 high risk subjects. Subjects at high
      risk for psychosis showed reduced gray matter (GM) volume as compared to controls
      in the right superior temporal gyrus, left precuneus, left medial frontal gyrus,
      right middle frontal gyrus, bilateral parahippocampal/hippocampal regions and
      bilateral anterior cingulate. High risk subjects who later developed a psychotic
      episode showed baseline GM volume reductions in the right inferior frontal gyrus
      and in the right superior temporal gyrus. CONCLUSIONS: GM volume reductions in
      temporo-parietal, bilateral prefrontal and limbic cortex are neuroanatomical
      correlates of an enhanced vulnerability to psychosis. Baseline GM reductions in
      superior temporal and inferior frontal areas are associated with later transition
      to psychosis.

PMID- 21168441
TI  - Comparison Evans Blue injection routes: Intravenous versus intraperitoneal, for
      measurement of blood-brain barrier in a mice hemorrhage model.
AB  - AIMS: Intracerebral hemorrhage is one of the most devastating subtypes of stroke,
      leaving survivors with severe neurological deficits. Disruption of the blood
      brain barrier (BBB) following hemorrhage results in the development of vasogenic
      brain edema, a most life-threatening event after such events as intracerebral
      hemorrhage (ICH). The Evans Blue assay is a popular method for the quantification
      of BBB disruption. Although this method is in common use, there are several
      protocols of the assay in the literature which vary in the route of
      administration, as well as the circulation time of the stain. In this study, we
      compared the amounts of accumulated stain in brain tissue following
      intraperitoneal versus intravenous injection at 0.5, 3 and 24h of circulation
      time. METHODS: 58 CD-1 mice were used. Animals were divided into ICH (N=42), sham
      groups (N=6) and naive (N=10). ICH animals received stereotactic injection of
      collagenase type VII into the right basal ganglia. Sham animals received only
      needle trauma. Evans Blue stain was injected 24h after collagenase injection or
      needle trauma. The consistency of ICH produced was characterized by estimation of
      hematoma volume via hemoglobin assay and neurological evaluation. RESULTS: The
      produced hematoma and neurological deficits were well comparable between
      different experimental groups. There was no statistically significant difference
      in the results of the Evans Blue assay with regard to administration route.
      CONCLUSIONS: The amount of Evans Blue stain accumulated in the brains of mice
      after ICH produced by collagenase injection was independent of the stain
      administration route.

PMID- 21168442
TI  - Detection of human adenovirus hexon antigen using carbon nanotube sensors.
AB  - Human adenoviruses (HAdVs) have been implicated in a wide range of diseases
      affecting primarily the respiratory, ocular and gastrointestinal systems. A rapid
      and efficient method for the detection of HAdV hexon antigen is described using
      carbon nanotube (CNT) sensors. Anti-HAdV antibody was immobilised on the reverse
      surface of a CNT sensor. As a control, non-specific mouse IgG was immobilised on
      another CNT sensor. I-V(gate) curves were measured after incubation of various
      concentrations of recombinant HAdVs hexon antigen with anti-HAdVs antibody
      immobilised or non-specific mouse IgG-immobilised sensors. The curves showed a
      positive shift that was dependent on the hexon antigen concentration in the anti
      HAdV antibody-immobilised sensor, whereas no such shift was observed in the non
      specific mouse IgG-immobilised sensor. The sensitivity of the CNT sensor method
      was greater than that of enzyme-linked immunosorbent assay. Hence, this method
      offers a new tool for HAdV detection by analysing antigen-antibody interactions.

PMID- 21168443
TI  - A differential ELISA based on recombinant immunodominant epitopes of the gE gene
      of SHV-1 in a baculovirus-insect cell system to discriminate between pigs
      infected naturally with pseudorabies and vaccinated pigs.
AB  - In the present study, the fragment corresponding to the immunodominant epitopes
      of the gE gene (gEpi) from the CL15 Argentinean strain of pseudorabies virus was
      expressed successfully in a baculovirus-insect cell system that contained the M6
      gene of Bluetongue virus, which encodes the NS1 nonstructural protein. This
      protein has the ability to polymerize into highly immunogenic tubules inside
      infected cells that can be purified at large quantities by ultracentrifugation.
      Previously, the NS1 protein has been expressed by fusing it to sequences derived
      from viruses, such as human immunodeficiency virus type 1, hepatitis B virus,
      bovine leukemia virus, foot-and-mouth disease virus and influenza A virus. In the
      present study, a recombinant protein was obtained containing the gEpi fused to
      NS1 (NS1-gEpi) and used it as ELISA antigen for detection of anti-gE antibodies
      in order to discriminate between infected and vaccinated animals. This is the
      first report where gEpi was expressed in this particular baculovirus-insect cell
      system.

PMID- 21168444
TI  - Prokaryotic expression and purification of HA1 and HA2 polypeptides for
      serological analysis of the 2009 pandemic H1N1 influenza virus.
AB  - Hemagglutinin (HA) is an important influenza virus surface antigen that is highly
      topical in influenza research. In the present study, the genes encoding the HA1
      and HA2 proteins from the 2009 pandemic influenza virus H1N1
      (A/California/04/2009(H1N1)) were cloned into a prokaryotic expression plasmid
      pCold-TF, and soluble fusion proteins containing H1N1 HA1 and HA2 were produced
      by transformed Escherichia coli. Western blot assays were used to examine the
      immunoreactivity of the recombinant proteins using polyclonal and monoclonal
      antibodies derived against the whole virus A/California/04/2009(H1N1).
      Recombinant protein immunoreactivity was also analyzed qualitatively by ELISA and
      hemagglutination inhibition using human serum samples. These results will aid
      future immunological and serological studies of the 2009 pandemic H1N1 virus HA.

PMID- 21168445
TI  - Attention, executive functioning and memory in normal aged rhesus monkeys.
AB  - Understanding how cognition declines in normal aging is vital in order to
      distinguish between normal cognitive decline due to aging and cognitive decline
      due to an age-related pathological process such as Parkinson's disease (PD).
      Several cognitive domains including memory, executive functioning and attention
      are all adversely affected with age in humans, as well as by PD, yet less is
      known about how these processes are affected by aging in non-human primates.
      Thus, in order to characterize baseline performance in aged primates prior to
      inducing Parkinson-like pathology, male rhesus macaques aged 15-22 years were
      tested on several tasks analogous to those used in cognitive aging studies in
      humans. The tasks included simple visual discrimination to assess learning and
      reference memory, discrimination reversal to assess cognitive flexibility and
      response inhibition, continuous performance to assess sustained visual attention,
      and attention set shifting to assess cognitive flexibility and set-shifting
      ability. Deficits were detected in some aspects of learning, cognitive
      flexibility, response inhibition and sustained visual attention, whereas
      reference memory and set-shifting did not appear to be affected. Additionally,
      there was a greater amount of variability in cognitive abilities across the aged
      animals than observed previously in young adult animals. These findings will form
      an important baseline for comparison with cognitive performance after PD-like
      pathology is superimposed on the normal aging process.

PMID- 21168446
TI  - Sensorimotor and cognitive function of a NEFL(P22S) mutant model of Charcot-Marie
      Tooth disease type 2E.
AB  - Charcot-Marie-Tooth (CMT) disease is the most frequently encountered hereditary
      disease causing sensorimotor neuropathies and slowly progressive muscle weakness
      and atrophy. The P22S mutation of the NEFL gene encoding the light polypeptide
      neurofilament (NFL) is associated with CMT. To understand more clearly the
      pathogenesis of sensorimotor dysfunction in CMT, we generated transgenic mice
      with the NEFL(P22S) mutation under the tet-off tetracycline regulated system with
      involvement of the Thy1 neuron-specific promoter. NEFL(P22S) transgenic mice
      exhibited extended duration of the hindlimb clasping response and gait anomalies,
      as well as sensorimotor deficits in stationary beam and suspended bar tests. In
      addition, the NEFL(P22S) mice were deficient in the reversal phase of left-right
      discrimination learning in a water maze. This model mimics some aspects of human
      CMT pathology and provides an opportunity of ameliorating CMT symptoms with
      experimental therapies.

PMID- 21168440
TI  - Time-dependent analysis of length of stay and mortality due to urinary tract
      infections in ten developing countries: INICC findings.
AB  - OBJECTIVES: To estimate the excess length of stay (LOS) and mortality in an
      intensive care unit (ICU) due to a Catheter associated urinary tract infections
      (CAUTI), using a statistical model that accounts for the timing of infection in
      29 ICUs from 10 countries: Argentina, Brazil, Colombia, Greece, India, Lebanon,
      Mexico, Morocco, Peru, and Turkey. METHODS: To estimate the extra LOS due to
      infection in a cohort of 69,248 admissions followed for 371,452 days in 29 ICUs,
      we used a multi-state model, including specific censoring to ensure that we
      estimate the independent effect of urinary tract infection, and not the combined
      effects of multiple infections. We estimated the extra length of stay and
      increased risk of death independently in each country, and then combined the
      results using a random effects meta-analysis. RESULTS: A CAUTI prolonged length
      of ICU stay by an average of 1.59 days (95% CI: 0.58, 2.59 days), and increased
      the risk of death by 15% (95% CI: 3, 28%). CONCLUSIONS: A CAUTI leads to a small
      increased LOS in ICU. The increased risk of death due to CAUTI may be due to
      confounding with patient morbidity.

PMID- 21168447
TI  - Aspects of static and dynamic motor function in peripheral nerve regeneration:
      SSI and CatWalk gait analysis.
AB  - Assessment of the therapeutic potential of interventions to bridge-repair
      peripheral nerve defects heavily relies on the demonstration of improved
      functional outcome. In the present study we used CatWalk gait analysis (locomotor
      test) and Static Sciatic Index (SSI) (static-toe-spread-test) to assess the
      behavioural benefits of autologous nerve transplantation (ANT) repair of 2-cm rat
      sciatic nerve defects (neurotmesis-lesion). A reproducible and standardised rat
      sciatic nerve crush lesion model (axonotmesis-lesion) was used to assess the
      extent of recovery supported by maximal axon regeneration (measured by SSI and
      CatWalk). Animals were behaviourally followed for a period of 10 weeks. SSI
      analysis showed that ANT induced a significant improvement in motor deficit from
      about -95 to -65, however, CatWalk analysis did not show any major indication of
      locomotor recovery. This discrepancy might suggest that improvements in static
      motor functions (such as toe spreading) could reflect an early indicator for the
      recovery of function. We also noted differences in axon regeneration including
      increased axon density, smaller axon diameters and thinner myelin sheaths in the
      distal region of the ANT in comparison to the equivalent region of crushed and
      normal nerves. This difference in axon regeneration may be related to the clearly
      improved toe spreading function. We conclude that SSI and CatWalk present
      different advantages and disadvantages for the assessment of motor recovery after
      bridge-repair of peripheral nerve defects.

PMID- 21168448
TI  - Role of Ca(V)2.1-mediated NMDA receptor signaling in the nucleus accumbens in
      spatial short-term memory.
AB  - Heterozygous rolling Nagoya (rol/+) mice with a Ca(V)2.1alpha1 mutation show
      normal Y-maze behavior. Intra-accumbens injection of N-methyl-d-aspartate (NMDA;
      0-2.0 MUg/side) induced similar spontaneous alternations in wild-type and rol/+
      mice; injections of NMDA receptor antagonist MK-801 (0.5 MUg/side) or Ca(V)2.1
      inhibitor levetiracetam (0.1 MUg/side) did not affect controls but decreased
      spatial cognition in rol/+ mice, suggesting that Ca(V)2.1-mediated NMDA receptor
      signaling in the nucleus accumbens is involved in short-term spatial learning.

PMID- 21168449
TI  - Novelty-induced enhancement in spatial memory: is infancy a critical period?
AB  - Development of many psychological functions is known to occur within a limited
      time window and beyond such a critical period, environmental stimulation has
      little or no effect. With a split-litter 2*2 factorial design in which neonatal
      and early adulthood novelty exposure were two within-litter factors, we examined
      whether infancy is a critical period for novelty exposure experience to induce a
      long-lasting functional enhancement in spatial memory and whether the known
      enhancement effect induced by early life experience can be further augmented by
      later adult experience. Spatial memory performance was evaluated in a three-day
      moving platform Morris water maze task. We found that the animals deprived of
      novelty exposure during infancy could nevertheless benefit from a delayed adult
      exposure and that the magnitude of this enhancement was comparable to the
      enhancement induced by neonatal exposure. This finding indicates that infancy is
      not a critical period beyond which novelty exposure will have little effect on
      enhancing spatial memory. Surprisingly, although both neonatal and adult
      experience alone produced enhancement in spatial memory performance, animals that
      experienced both neonatal and adult exposures showed no statistically significant
      difference from those who had none. This finding indicates that the cumulative
      effect of neonatal and early adulthood experience of novelty is not additive but
      a result of non-linear interaction and that knowing the effect of a single-stage
      intervention does not allow one to predict the final developmental outcome
      without taking into consideration events occurring before or after.

PMID- 21168450
TI  - A novel dual Dbp5/DDX19 homologue from Plasmodium falciparum requires Q motif for
      activity.
AB  - Helicases are ubiquitous essential enzymes which have significant role in the
      nucleic acid metabolism. Using in silico approaches in the recent past we have
      identified a number of helicases in the Plasmodium falciparum genome. In the
      present study we report purification and detailed characterization of a novel
      helicase from P. falciparum. Our results indicate that this helicase is a
      homologue of Dbp5 and DDX19 from yeast and human, respectively. The biochemical
      characterization shows that it contains DNA and RNA unwinding, nucleic acid
      dependent ATPase and RNA binding activities. It is interesting to note that this
      enzyme can unwind DNA duplexes in both 5' to 3' and 3' to 5' directions. Using
      truncated derivatives we further show that Q motif is essentially required for
      all of its activities. These studies should make an important contribution in
      understanding the enzymes involved in nucleic acid metabolism in the parasite.

PMID- 21168451
TI  - Growth of Spirulina platensis enhanced under intermittent illumination.
AB  - The growth characteristics of microalgae under different light conditions
      (continuous or intermittent) are essential information for photobioreactor design
      and operation. In this study, we constructed a thin-layer (10mm) flat plate
      photobioreactor device with a light/dark (L/D) alternation system to investigate
      the growth of Spirulina platensis under two different light regimes: (1)
      continuous illumination in a wide range of light intensities (1.00-77.16 mW cm(
      2)); (2) intermittent illumination in medium frequency (0.01-20 Hz). Specific
      growth rate and light efficiency based on biomass production were determined for
      each round of experiment. Four regions (light limited region, intermediate
      region, light saturated region and light inhibition region) were recognized
      according to the results under continuous illumination. Under intermittent
      illumination, when L/D frequency increased from 0.01 Hz to 20 Hz, specific growth
      rate and light efficiency were enhanced. However, the enhancement was different,
      depending on the applied light intensity and light fraction. The higher the light
      intensity, the greater the enhancement would be when L/D frequency increased from
      0.01 Hz to 20 Hz; and the higher the light intensity, the lower the light
      fractions is needed to maintain light efficiency as high as that under continuous
      illumination in light limited region.

PMID- 21168452
TI  - Thermostable tag (TST) protein expression system: engineering thermotolerant
      recombinant proteins and vaccines.
AB  - Methods to increase temperature stability of vaccines and adjuvants are needed to
      reduce dependence on cold chain storage. We report herein creation and
      application of pVEX expression vectors to improve vaccine and adjuvant
      manufacture and thermostability. Defined media fermentation yields of 6g/L
      thermostable toll-like receptor 5 agonist flagellin were obtained using an IPTG
      inducible pVEX-flagellin expression vector. Alternative pVEX vectors encoding
      Pyrococcus furiosus maltodextrin-binding protein (pfMBP) as a fusion partner
      improved Influenza hemagglutinin antigen vaccine solubility and thermostability.
      A pfMBP hemagglutinin HA2 domain fusion protein was a potent immunogen.
      Manufacturing processes that combined up to 5 g/L defined media fermentation
      yields with rapid, selective, thermostable pfMBP fusion protein purification were
      developed. The pVEX pfMBP-based thermostable tag (TST) platform is a generic
      protein engineering approach to enable high yield manufacture of thermostable
      recombinant protein vaccine components.

PMID- 21168453
TI  - A virulent strain of porcine reproductive and respiratory syndrome virus does not
      up-regulate interleukin-10 levels in vitro or in vivo.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) causes reproductive
      failure and respiratory illness in infected pigs. It has been postulated that the
      ability of PRRSV to induce the anti-inflammatory cytokine interleukin-10 (IL-10)
      in macrophages of infected pigs would be important for PRRSV immunopathogenesis,
      although this property would be variable and might be dependent on the strain.
      Several strains were reported to induce IL-10 in infected macrophages while
      others would not. In this study, we analyzed the IL-10 expression during in vitro
      and in vivo infections by a well-characterized virulent strain of PRRSV, vFL12,
      which is derived from an infectious clone. Our results showed that the vFL12
      strain did not up-regulate IL-10 at mRNA or protein levels in either infected
      macrophages or dendritic cells in vitro. Furthermore, immunofluorescence staining
      for IL-10 on tonsil sections of PRRSV-infected pigs did not produce any evidence
      of IL-10 induction in PRRSV-infected cells or in bystander cells of the lymphoid
      tissues. Hence, based on these results obtained with a well-characterized highly
      pathogenic PRRSV strain it may be concluded that the induction of IL-10 release
      is not a part of the PRRSV virulence mechanisms.

PMID- 21168454
TI  - Reduced frequencies of NKp30+NKp46+, CD161+, and NKG2D+ NK cells in acute HCV
      infection may predict viral clearance.
AB  - BACKGROUND & AIMS: While the majority of HCV-infected patients progress to
      chronic hepatitis, a small fraction of individuals are able to clear the virus.
      Resolution of infection occurs within the first few weeks to months of infection,
      suggesting that innate immune functions may be critical for early control.
      Epidemiologic data support a role for particular NK cell receptor bearing
      populations in this control, yet the mechanism by which NK cells respond to HCV
      early in infection is unknown. METHODS: Changes in the phenotype and function of
      NK cells were investigated in a cohort of 43 individuals identified during
      various stages of HCV infection with different clinical outcomes. RESULTS: Acute,
      chronic, and resolved HCV infections were characterized by an expansion of
      CD56(neg) NK cells. Furthermore, increased levels of HLA-C-binding KIR(+) NK
      cells were observed in HCV resolvers, while all stages of HCV infection were
      associated with reduced percentages of NKG2D(+), NKp30(+), and NKp46(+) NK cells,
      and a slight increase in the ability of NK cells to respond to target cells
      bearing the ligands for these receptors. In contrast, NKG2A(+) and CD94(+) NK
      cells were elevated in acute and chronic HCV infection, but not in resolved
      infection. Most importantly, in acute infection, lower frequencies of NKp30(+),
      NKp46(+), CD161(+), and NKG2D(+) NK cells were observed in patients who were
      subsequently able to clear HCV infection than in those becoming chronically
      infected. CONCLUSIONS: These data implicate particular populations of NK cells in
      the early control and clearance of HCV infection.

PMID- 21168455
TI  - Potent antifibrotic activity of mTOR inhibitors sirolimus and everolimus but not
      of cyclosporine A and tacrolimus in experimental liver fibrosis.
AB  - BACKGROUND & AIMS: Recurrence of chronic hepatitis C and progressive fibrosis in
      liver transplants is frequent and impairs both graft and patient survival.
      Whether or not the choice of immunosuppression affects progression of fibrosis
      remains unclear. The aim of the present study was to compare the potential of the
      commonly used immunosuppressants to halt experimental liver fibrosis progression.
      METHODS: To induce liver fibrosis, rats underwent bile duct ligation and
      treatment with sirolimus (2mg/kg), everolimus (3mg/kg), tacrolimus (1mg/kg), and
      cyclosporin A (10mg/kg) daily for 5 weeks. Fibrosis, inflammation, and portal
      pressure were evaluated by histology, hydroxyproline levels, morphometry,
      hemodynamics, and hepatic gene expression. RESULTS: Sirolimus and everolimus
      decreased fibrosis up to 70%, improved portal pressure, reduced ascites, and
      showed potent down-regulation of pro-fibrogenic genes, paralleled by a strong
      increase in matrix degradation (collagenase) activity; in contrast, tacrolimus
      and cyclosporine A had no or even aggravating effects on liver fibrosis in rats.
      CONCLUSIONS: mTOR inhibition by sirolimus and everolimus in experimental liver
      fibrosis associates with significantly less fibrosis progression and portal
      hypertension than treatment with calcineurin inhibitors tacrolimus and
      cyclosporine A. These data suggest that the selection of the immunosuppressant
      could impact the recurrence of fibrosis in liver allografts.

PMID- 21168456
TI  - Ursolic acid ameliorates hepatic fibrosis in the rat by specific induction of
      apoptosis in hepatic stellate cells.
AB  - BACKGROUND & AIMS: Specific induction of cell death in activated hepatic stellate
      cells (HSCs) is a promising therapeutic strategy for hepatic fibrosis. In this
      study, we evaluated the cell-killing effect of ursolic acid (UA), a pentacyclic
      triterpenoid, in activated HSCs both in vitro and in vivo. METHODS: Culture
      activated rat HSCs were treated with UA (0-40MUM), and the mechanisms of cell
      death were evaluated. The cell killing effect of UA on activated HSCs in rats
      chronically treated with thioacetamide (TAA) was detected by dual staining of TdT
      mediated dUTP nick-end labeling (TUNEL) and smooth muscle alpha-actin (alphaSMA)
      immunohistochemistry, and resolution of hepatic fibrosis was evaluated. Further,
      the protective effects of UA on progression of hepatic fibrosis caused by TAA and
      bile duct ligation (BDL) were evaluated. RESULTS: UA induced apoptotic cell death
      in culture-activated HSCs, but not in isolated hepatocytes and quiescent HSCs.
      Mitochodrial permeability transition (MPT) preceded the cleavage of caspase-3 and
      -9 following UA treatment. UA also decreased phosphorylation levels of Akt, and
      diminished nuclear localization of NFkappaB in these cells. In rats pretreated
      with TAA for 6weeks, a single injection of UA induced remarkable increases in
      TUNEL- and alphaSMA-dual-positive cells in 24h, and significant regression of
      hepatic fibrosis within 48h. Moreover, UA ameliorated hepatic fibrogenesis caused
      by both chronic TAA administration and BDL. CONCLUSIONS: UA ameliorated
      experimental hepatic fibrosis most likely through specific induction of apoptosis
      in activated HSCs. It is therefore postulated that UA is a potential therapeutic
      reagent for resolution of hepatic fibrosis.

PMID- 21168457
TI  - PI(3)K/PTEN/AKT pathway.

PMID- 21168458
TI  - Overexpression of von Hippel-Lindau protein synergizes with doxorubicin to
      suppress hepatocellular carcinoma in mice.
AB  - BACKGROUND & AIMS: Hypoxia-inducible factors (HIFs) and nuclear factor-kappaB (NF
      kappaB) regulate genes involved in carcinogenesis and progression of cancers
      including hepatocellular carcinoma (HCC). The von Hippel-Lindau (VHL) protein
      (pVHL) targets HIFalpha subunits for destruction and participates in modulating
      the activity of NF-kappaB. The present study aimed to investigate whether the
      overexpression of pVHL synergizes with doxorubicin in the treatment of HCC.
      METHODS: Overexpression of pVHL was induced by infecting mouse HCC Hepa1-6 and
      H22 cells, or injecting subcutaneous Hepa1-6 tumors in C57BL/c mice, with
      adenoviral vectors encoding mouse VHL gene. Cell proliferation, apoptosis,
      tumoral angiogenesis, and gene expression and DNA-binding activity of NF-kappaB
      were examined. The therapeutic effects of pVHL were also evaluated in orthotopic
      Hepa1-6 tumors by intraportal delivery of Ad-VHL. RESULTS: Ad-VHL enhanced the
      anti-tumor activity of doxorubicin by inhibiting cell proliferation, and causing
      cell cycle arrest and apoptosis. The Ad-VHL infection downregulated HIF-1alpha
      and HIF-2alpha expression, and inhibited NF-kappaB activity and the expression of
      genes involved in apoptosis, proliferation, angiogenesis, invasion, and
      metastasis. Injection of Ad-VHL into HCC tumors augmented doxorubicin-induced
      suppression of tumor growth by inhibiting cell proliferation and tumor
      angiogenesis, and by inducing cell apoptosis. Effects on the expression of
      HIFalphas, activity of NF-kappaB, and their downstream genes were in accordance
      with the in vitro findings. Intraportal injection of Ad-VHL enhanced the efficacy
      of doxorubicin to suppress the growth of orthotopic liver tumors. CONCLUSIONS: By
      targeting HIF and NF-kappaB, overexpression of pVHL enhances the efficacy of
      doxorubicin, and warrants consideration as a potential therapeutic strategy for
      treating HCC.

PMID- 21168459
TI  - Variant adiponutrin (PNPLA3) represents a common fibrosis risk gene: non-invasive
      elastography-based study in chronic liver disease.
AB  - BACKGROUND & AIMS: Recent genome-wide association studies have identified the
      variant p.I148M of the adiponutrin gene PNPLA3 as a risk factor for developing
      severe forms of non-alcoholic and alcoholic liver diseases. The risk allele
      confers an increased risk for fatty liver disease and elevated serum
      aminotransferase activities reflecting liver injury. In the current elastography
      based study, we investigate variant adiponutrin as genetic determinant of liver
      fibrosis, the hallmark of all chronic liver diseases. METHODS: In this
      observational cross-sectional study, we staged 899 patients with different
      chronic liver diseases non-invasively by transient elastography (Fibroscan) and
      genotyped them for variant adiponutrin (rs738409) by PCR-based assays. A subgroup
      of 229 patients consented to percutaneous liver biopsy, validating the accuracy
      of elastography in staging fibrosis (rho=0.743, p<0.01). RESULTS: Carriers of
      distinct p.I148M adiponutrin genotypes display significant (p=0.017) differences
      in liver stiffness determined by elastography. In particular, individuals
      carrying the allele [G] are at higher risk of developing liver cirrhosis defined
      by stiffness values >=13.0kPa (OR=1.56, p=0.005). Of note, the PNPLA3 risk
      variant advances fibrosis in the total cohort as well as in the subgroups of
      patients with viral hepatitis and non-viral liver diseases and contributes 16% of
      the total cirrhosis risk. CONCLUSIONS: The adiponutrin risk variant is a common
      genetic determinant of progressive liver fibrosis. Our results underpin non
      invasive follow-up for individuals with chronic liver disease at-risk for
      developing advanced fibrosis and cirrhosis.

PMID- 21168460
TI  - Early interplay of intra-hepatic iron and insulin resistance in children with non
      alcoholic fatty liver disease.
AB  - BACKGROUND & AIMS: The liver is a crucial organ at the crossroads of iron and
      glucose metabolism. The aim of the study was to assess intra-hepatic iron in
      young patients with non-alcoholic fatty liver disease (NAFLD) and its association
      with insulin resistance and severity of liver damage. METHODS: Intrahepatic iron
      content was assessed (Pearl's stain grade) in 66 patients (41 males, age 3.3
      17.6years) with biopsy-proven NAFLD. Mutations of the Hereditary Hemochromatosis
      (HFE) gene were determined by sequence allele-specific polymerase chain reaction.
      Insulin resistance was estimated by means of the Oral Glucose Tolerance Test and
      the Insulin Sensitivity Index (ISI); the Insulino-Genic Index was also
      calculated. Tumor necrosis factor-alpha and interleukin-6 were measured. RESULTS:
      Low-mild intra-hepatic iron deposition was observed in one out of five children
      (n=15, 22%), and it was not associated with HFE mutations, carried by 17 patients
      (26%). Among carriers of HFE mutations, four had siderosis. No abnormalities were
      observed in systemic indices of iron balance. Serum ferritin was within normal
      adult ranges in all patients (33.6+/-7.6ng/ml), but it was correlated with ISI
      (r(o)=-0.361; p=0.003). No significant difference was observed in insulin
      sensitivity, iron balance, inflammatory milieu, and liver histology between
      patients with and without hepatic siderosis. CONCLUSIONS: In young obese
      individuals with NAFLD, despite normal peripheral iron parameters, mild intra
      hepatic iron deposition is a frequent finding, but it is not associated with
      insulin resistance or severity of liver damage. Longitudinal studies are required
      to define the long-term relevance of these findings.

PMID- 21168461
TI  - Identification of a cysteine-rich antimicrobial peptide from salivary glands of
      the tick Rhipicephalus haemaphysaloides.
AB  - The presence of an effective immune response in the hemocoel of ticks is crucial
      for survival, as it prevents the invasion of pathogens throughout the animal's
      body. Antimicrobial peptides (AMPs) play an important role in this response by
      rapidly killing invading microorganisms. In this study, a subtraction
      hybridization cDNA library was constructed from the salivary glands of the unfed
      and fed female tick Rhipicephalus haemaphysaloides, and a novel cysteine-rich AMP
      designated Rhamp (R. haemaphysaloides antimicrobial peptide) was isolated and
      identified. The Rhamp was encoded by a gene with an open reading frame of 303 bp
      which encoded a mature peptide with 8 kDa molecular weight. No identity was found
      by BLAST search to any database entries. The sequence encoding the Rhamp was
      subcloned into the pGEX-4T vector and expressed in Escherichia coli. The
      recombinant protein of Rhamp showed chymotrypsin and elastase-inhibitory activity
      and markedly inhibited the growth of gram-negative bacteria, including
      Pseudomonas aeruginosa, Salmonella typhimurium, and E. coli. Moreover, the
      recombinant protein also exerted low hemolytic activity. These results indicate
      the Rhamp is a novel antimicrobial peptide with proteinase activity from the tick
      R. haemaphysaloides.

PMID- 21168462
TI  - Vitamin D receptor gene methylation is associated with ethnicity, tuberculosis,
      and TaqI polymorphism.
AB  - The Vitamin D receptor (VDR) gene encodes a transcription factor which, on
      activation by vitamin D, modulates diverse biologic processes, including calcium
      homeostasis and immune function. Genetic variation involving VDR shows striking
      differences in allele frequency between populations and has been associated with
      disease susceptibility, including tuberculosis and autoimmunity, although results
      have often been conflicting. We hypothesized that methylation of VDR may be
      population specific and that the combination of differential methylation and
      genetic variation may characterize tuberculosis (TB) predisposition. We use
      bisulfite conversion and/or pyrosequencing to analyze the methylation status of
      17 CpGs of VDR and to genotype 7 SNPs in the 3' CpG Island (CpG island [CGI]
      1060), including the commonly studied SNPs ApaI (rs7975232) and TaqI (rs731236).
      We show that, for lymphoblastoid cell lines from two ethnically diverse
      populations (Yoruba from HapMap, n = 30 and Caucasians, n = 30) together with TB
      cases (n = 32) and controls (n = 29) from the Venda population of South Africa,
      there are methylation variable positions in the 3' end that significantly
      distinguish ethnicity (9/17 CpGs) and TB status (3/17 CpGs). Moreover,
      methylation status shows complex association with TaqI genotype highlighting the
      need to consider both genetic and epigenetic variants in genetic studies of VDR
      association with disease.

PMID- 21168463
TI  - Evaluation and prediction of pharmacokinetics of PFOA and PFOS in the monkey and
      human using a PBPK model.
AB  - Perfluoroalkyl acid carboxylates and sulfonates (PFAAs) have many consumer and
      industrial applications. The persistence and widespread distribution of these
      compounds in humans have brought them under intense scrutiny. Limited
      pharmacokinetic data is available in humans; however, human data exists for two
      communities with drinking water contaminated by PFAAs. Also, there is
      toxicological and pharmacokinetic data for monkeys, which can be quite useful for
      cross-species extrapolation to humans. The goal of this research was to develop a
      physiologically-based pharmacokinetic (PBPK) model for PFOA and PFOS for monkeys
      and then scale this model to humans in order to describe available human drinking
      water data. The monkey model simulations were consistent with available PK data
      for monkeys. The monkey model was then extrapolated to the human and then used to
      successfully simulate the data collected from residents of two communities
      exposed to PFOA in drinking water. Human PFOS data is minimal; however, using the
      half-life estimated from occupational exposure, our model exhibits reasonable
      agreement with the available human serum PFOS data. It is envisioned that our
      PBPK model will be useful in supporting human health risk assessments for PFOA
      and PFOS by aiding in understanding of human pharmacokinetics.

PMID- 21168464
TI  - Risperidone oral solution versus standard tablets for the acute treatment of
      patients with schizophrenia.
AB  - The time required to attain the maximum plasma level of risperidone (RIS) is
      shorter for RIS oral solution (OS) than for RIS standard tablets (ST), although
      both forms have equal bioavailability. The objective of this study was to clarify
      whether RIS-OS shows a faster onset of efficacy and lower adverse events than RIS
      ST. The two forms of risperidone were compared with respect to effectiveness
      including a speed of response, efficacy and tolerability. An open-label, 24-week,
      multicentre, randomized, flexible-dose study comparing the RIS-OS (mean dose, 3.7
      mg; N=44) to the RIS-ST (mean dose, 3.7 mg; N=37) in acutely ill patients with
      schizophrenia showed no differences. Outcome measures included psychopathology,
      tolerability (extrapyramidal symptoms and serum prolactin), and Drug Attitude
      Inventory. This study was conducted between October 2006 and October 2008. Both
      RIS-OS- and RIS-ST-treated patients showed statistically significant reductions
      from the baseline in the mean scores of the Positive and Negative Syndrome Scale
      (PANSS)-total and PANSS-excite component, with no statistically significant
      differences between the treatment groups. The accumulated treatment response
      ratio was similar between the two groups. There was no significant difference in
      the Drug-Induced Extrapyramidal Symptom Scale score or serum prolactin increase
      between the treatment groups, but RIS-OS appeared to induce less serum prolactin
      increase than RIS-ST in drug-naive female patients. Because there is no
      theoretical reason why this should be so, these results will require confirmation
      from a double-blind study in a larger sample. No significant difference was
      observed in the subjective drug attitude between the two groups. The original
      hypothesis that RIS-OS shows an earlier onset of efficacy or less adverse events
      than RIS-ST was not supported in this study. Subsequent studies should carefully
      establish the differences among various forms of antipsychotic drugs.

PMID- 21168465
TI  - Gene-environment interactions and construct validity in preclinical models of
      psychiatric disorders.
AB  - The contributions of genetic risk factors to susceptibility for brain disorders
      are often so closely intertwined with environmental factors that studying genes
      in isolation cannot provide the full picture of pathogenesis. With recent
      advances in our understanding of psychiatric genetics and environmental modifiers
      we are now in a position to develop more accurate animal models of psychiatric
      disorders which exemplify the complex interaction of genes and environment. Here,
      we consider some of the insights that have emerged from studying the relationship
      between defined genetic alterations and environmental factors in rodent models. A
      key issue in such animal models is the optimization of construct validity, at
      both genetic and environmental levels. Standard housing of laboratory mice and
      rats generally includes ad libitum food access and limited opportunity for
      physical exercise, leading to metabolic dysfunction under control conditions, and
      thus reducing validity of animal models with respect to clinical populations. A
      related issue, of specific relevance to neuroscientists, is that most standard
      housed rodents have limited opportunity for sensory and cognitive stimulation,
      which in turn provides reduced incentive for complex motor activity. Decades of
      research using environmental enrichment has demonstrated beneficial effects on
      brain and behavior in both wild-type and genetically modified rodent models,
      relative to standard-housed littermate controls. One interpretation of such
      studies is that environmentally enriched animals more closely approximate average
      human levels of cognitive and sensorimotor stimulation, whereas the standard
      housing currently used in most laboratories models a more sedentary state of
      reduced mental and physical activity and abnormal stress levels. The use of such
      standard housing as a single environmental variable may limit the capacity for
      preclinical models to translate into successful clinical trials. Therefore, there
      is a need to optimize 'environmental construct validity' in animal models, while
      maintaining comparability between laboratories, so as to ensure optimal
      scientific and medical outcomes. Utilizing more sophisticated models to elucidate
      the relative contributions of genetic and environmental factors will allow for
      improved construct, face and predictive validity, thus facilitating the
      identification of novel therapeutic targets.

PMID- 21168466
TI  - Effects of risperidone, quetiapine and ziprasidone on ethanol withdrawal syndrome
      in rats.
AB  - Comorbid substance use in schizophrenic patients is common, and substance
      dependence is a predictive factor for psychosis. The present study was designed
      to investigate the effects of risperidone, quetiapine and ziprasidone, atypical
      antipsychotic drugs, on ethanol withdrawal syndrome (EWS) in rats. Adult male
      Wistar rats were used in the study. Ethanol (7.2%, v/v) was given to rats via a
      liquid diet for 21 days. An isocaloric liquid diet without ethanol was given to
      control rats. Risperidone (1 and 2 mg/kg), quetiapine (8 and 16 mg/kg),
      ziprasidone (0.5 and 1 mg/kg) and vehicle were injected into rats
      intraperitoneally at 1.5 and 5.5 h of ethanol withdrawal. At the 2nd, 4th and 6th
      hours of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs
      that included locomotor hyperactivity, stereotyped behaviors, abnormal gait and
      posture, tail stiffness and agitation were recorded or rated. Following the
      observations at the 6th hour, the rats were tested for audiogenic seizures. All
      three drugs had some significant inhibitory effects on EWS-induced behavioral
      signs beginning at the 2nd hour of withdrawal. The drugs also significantly
      reduced the incidence of audiogenic seizures. Overall, risperidone and quetiapine
      seemed to be more effective than ziprasidone in ameliorating the withdrawal
      signs. Doses of the drugs used in the present study did not produce any
      significant changes in locomotor activities of naive rats. Our results suggest
      that risperidone, quetiapine and ziprasidone had beneficial effects on EWS in
      rats. Thus, these drugs may be helpful for controlling withdrawal signs in
      ethanol-dependent patients.

PMID- 21168467
TI  - Neuroprotective effects of Eriobotrya japonica against beta-amyloid-induced
      oxidative stress and memory impairment.
AB  - The generation of oxygen free radicals and oxidative damage is believed to be
      involved in the pathogenesis of neurodegenerative disorders. Eriobotrya japonica
      has been used to treat several diseases in East Asia. In this study, we
      investigated the protective effect of an E. japonica extract against Abeta
      peptide-induced oxidative stress. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay
      demonstrated that the E. japonica extract scavenged approximately 40% of DPPH
      radicals. Also, treatment of the E. japonica extract inhibited Abeta(1-42)
      mediated neuronal cell death. Furthermore, treatment of E. japonica extract
      efficiently suppressed the increase in intracellular ROS triggered by the Abeta(1
      42) peptide. Importantly, mice pre-treated with the E. japonica extract showed
      restoration of alternation behavior and reversal of Abeta(1-42)-induced memory
      impairment. Consequently, the E. japonica extract substantially inhibited the
      increase in lipid peroxidation and restored superoxide dismutase activity. These
      results suggest that E. japonica protects from oxidative stress and cognitive
      deficits induced by the Abeta peptide.

PMID- 21168469
TI  - TET genes: new players in DNA demethylation and important determinants for
      stemness.
AB  - Stem cells are defined as cells that have the ability to perpetuate themselves
      through self-renewal and to generate functional mature cells by differentiation.
      During each stage, coordinated gene expression is crucial to maintain the balance
      between self-renewal and differentiation. Disturbance of this accurately balanced
      system can lead to a variety of malignant disorders. In mammals, DNA cytosine-5
      methylation is a well-studied epigenetic pathway that is catalyzed by DNA
      methyltransferases and is implicated in the control of balanced gene expression,
      but also in hematological malignancies. In this review, we focus on the TET (ten
      eleven-translocation) genes, which recently were identified to catalyze the
      conversion of cytosine-5 methylation to 5-hydroxymethyl-cytosine, an intermediate
      form potentially involved in demethylation. In addition, members of the TET
      family are playing a role in ES cell maintenance and inner cell mass cell
      specification and were demonstrated to be involved in hematological malignancies.
      Recently, a correlation between low genomic 5-hydroxymethyl-cytosine and TET2
      mutation status was shown in patients with myeloid malignancies.

PMID- 21168468
TI  - Effective mobilization of hematopoietic progenitor cells in G-CSF mobilization
      defective CD26-/- mice through AMD3100-induced disruption of the CXCL12-CXCR4
      axis.
AB  - OBJECTIVE: We previously reported that inhibition or loss of CD26
      (DPPIV/dipeptidylpeptidase IV) results in a defect in normal mobilization of
      hematopoietic stem and progenitor cells induced by granulocyte-colony stimulating
      factor (G-CSF). This suggests that CD26 is a necessary component of the
      mobilization pathway. Our goal in this study was to determine whether
      mobilization can be induced by the CXCR4 antagonist AMD3100 in mice lacking CD26
      (CD26(-/-)). MATERIALS AND METHODS: Ten week old CD26(-/-) and C57BL/6 mice
      received a subcutaneous injection of AMD3100. One hour post-injection the mice
      were euthanized and peripheral blood and bone marrow were collected and
      evaluated. RESULTS: AMD3100 mobilizes hematopoietic progenitors into the
      peripheral blood of CD26(-/-) and mice. CONCLUSIONS: Our finding that AMD3100
      rapidly mobilizes hematopoietic progenitor cells from the bone marrow into the
      periphery in CD26-deficient transgenic mice that otherwise exhibit a mobilization
      defect in response to G-CSF suggests that: (1) CD26 is downstream of G-CSF but
      upstream of the CXCL12-CXCR4 axis and (2) AMD3100 can be used as a single agent
      to mobilize hematopoietic stem and progenitor cells in normal donors or patients
      that have an intrinsic defect in their response to G-CSF treatment. Stem cell
      transplants are often the only curative treatment in some cancer patients. The
      ability to perform the transplantation and its success is dependent on the
      ability to mobilize adequate numbers of hematopoietic progenitor cells. The use
      of AMD3100 as a single agent would give patients or donors an additional option
      for a successful stem cell transplant.

PMID- 21168470
TI  - A multiorganism based method for Bayesian gene network estimation.
AB  - The primary goal of this article is to infer genetic interactions based on gene
      expression data. A new method for multiorganism Bayesian gene network estimation
      is presented based on multitask learning. When the input datasets are sparse, as
      is the case in microarray gene expression data, it becomes difficult to separate
      random correlations from true correlations that would lead to actual edges when
      modeling the gene interactions as a Bayesian network. Multitask learning takes
      advantage of the similarity between related tasks, in order to construct a more
      accurate model of the underlying relationships represented by the Bayesian
      networks. The proposed method is tested on synthetic data to illustrate its
      validity. Then it is iteratively applied on real gene expression data to learn
      the genetic regulatory networks of two organisms with homologous genes.

PMID- 21168471
TI  - Venous varicosities in the jejunum.

PMID- 21168472
TI  - Reactive oxygen and nitrogen species balance in the determination of thyroid
      hormones-induced cardiac hypertrophy mediated by renin-angiotensin system.
AB  - Role of reactive oxygen species (ROS)/nitric oxide (NO) balance and renin
      angiotensin system in mediating cardiac hypertrophy in hyperthyroidism was
      evaluated in an in vivo and in vitro experimental model. Male Wistar rats were
      divided into four groups: control, thyroid hormone, vitamin E (or Trolox, its
      hydrosoluble analogue), thyroid hormone+vitamin E. Angiotensin II receptor
      (AT1/AT2) gene expression, immunocontent of AT1/AT2 receptors, angiotensinogen,
      NADPH oxidase (Nox2), and nitric oxide synthase isoforms, as well as ROS
      concentration (hydrogen peroxide and superoxide anion) were quantified in
      myocardium. Thyroid hormone increased ROS and NO metabolites, iNOS, nNOS and eNOS
      isoforms and it was accompanied by cardiac hypertrophy. AT1/AT2 expression and
      the immunocontent of angiotensinogen and Nox2 were enhanced by thyroid hormone.
      Antioxidants reduced ROS levels, Nox2, AT1/AT2, NOS isoforms and cardiac
      hypertrophy. In conclusion, ROS/NO balance may play a role in the control of
      thyroid hormone-induced cardiac hypertrophy mediated by renin-angiotensin system.

PMID- 21168473
TI  - Directionality index of neural information flow as a measure of synaptic
      plasticity in chronic unpredictable stress rats.
AB  - This investigation examined whether the directionality of neural information flow
      could be used to index the measurement of synaptic plasticity in the chronic
      unpredictable stress (CUS) animals. Evolution map approach (EMA) was employed to
      determine the direction of information flow between the cortex and thalamus,
      while the experiment was performed by inducing long-term potentiation of the
      thalamocortical pathway after recording intracranial EEG at the same two
      positions in Wistar rats of both normal and stressed groups. The results showed
      that the coupling direction index was significantly diverted in stressed state
      compared to that in normal state, while the strength of thalamus driving frontal
      cortex was considerably reduced in the rats of CUS model. Moreover, the data
      obtained from LTP experiment exhibited that chronic stress decreased medial
      prefrontal cortex (mPFC) synaptic plasticity, which was certainly in accordance
      with the EEG findings. These results demonstrated that using EMA measurement,
      directionality index of neural information flow may be as a measure of synaptic
      plasticity.

PMID- 21168474
TI  - Protection by borneol on cortical neurons against oxygen-glucose
      deprivation/reperfusion: involvement of anti-oxidation and anti-inflammation
      through nuclear transcription factor kappaappaB signaling pathway.
AB  - Borneol, a terpene and bicyclic organic compound found in several species, can
      easily penetrate the blood-brain barrier (BBB) and helps the absorption of many
      agents through BBB in the brain, but there has been no study about its direct
      action on neurons in the CNS. In the present study, we used an in vitro ischemic
      model of oxygen-glucose deprivation followed by reperfusion (OGD/R) to
      investigate the neuroprotective effects of borneol and the related mechanisms. We
      demonstrated that borneol reversed OGD/R-induced neuronal injury, nuclear
      condensation, intracellular reactive oxygen species (ROS) generation, and
      mitochondrial membrane potential dissipation. The elevation of nitric oxide (NO),
      the increase of inducible nitric oxide synthase (iNOS) enzymatic activity and the
      upregulation of iNOS expression were also attenuated by borneol. The inhibition
      of caspase-related apoptotic signaling pathway was consistently involved in the
      neuroprotection afforded by borneol. Meanwhile, borneol inhibited proinflammatory
      factor release and IkappaBalpha degradation, and blocked nuclear transcription
      factor kappaappaB (NF-kappaB) p65 nuclear translocation induced by OGD/R. On the
      other hand, borneol did not show obvious effect on the inhibition of phospho
      IKKalpha activation. Furthermore, it failed to affect the OGD/R-induced enhanced
      level of phospho-SAPK/JNK. In conclusion, our study indicated that borneol
      protects against cerebral ischemia/reperfusion injury through multifunctional
      cytoprotective pathways. The mechanisms of this reversal from OGD/R may be
      involved in the alleviation of intracellular ROS and iNOS/NO pathway, inhibition
      of inflammatory factor release and depression of caspase-related apoptosis. Among
      these effects, the inhibition of IkappaBalpha-NF-kappaB and translocation
      signaling pathway might play a significant role in the neuroprotection of
      borneol.

PMID- 21168475
TI  - Activation of dopamine D3 receptors inhibits reward-related learning induced by
      cocaine.
AB  - Memories of learned associations between the rewarding properties of drugs and
      environmental cues contribute to craving and relapse in humans. The
      mesocorticolimbic dopamine (DA) system is involved in reward-related learning
      induced by drugs of abuse. DA D3 receptors are preferentially expressed in
      mesocorticolimbic DA projection areas. Genetic and pharmacological studies have
      shown that DA D3 receptors suppress locomotor-stimulant effects of cocaine and
      reinstatement of cocaine-seeking behaviors. Activation of the extracellular
      signal-regulated kinase (ERK) induced by acute cocaine administration is also
      inhibited by D3 receptors. How D3 receptors modulate cocaine-induced reward
      related learning and associated changes in cell signaling in reward circuits in
      the brain, however, have not been fully investigated. In the present study, we
      show that D3 receptor mutant mice exhibit potentiated acquisition of conditioned
      place preference (CPP) at low doses of cocaine compared to wild-type mice.
      Activation of ERK and CaMKIIalpha, but not the c-Jun N-terminal kinase and p38,
      in the nucleus accumbens, amygdala and prefrontal cortex is also potentiated in
      D3 receptor mutant mice compared to that in wild-type mice following CPP
      expression. These results support a model in which D3 receptors modulate reward
      related learning induced by low doses of cocaine by inhibiting activation of ERK
      and CaMKIIalpha in reward circuits in the brain.

PMID- 21168477
TI  - Preparation and evaluation of zinc-pectin-chitosan composite particles for drug
      delivery to the colon: role of chitosan in modifying in vitro and in vivo drug
      release.
AB  - Zinc-pectin-chitosan composite microparticles were designed and developed as
      colon-specific carrier. Resveratrol was used as model drug due to its potential
      activity on colon diseases. Formulations were produced by varying different
      formulation parameters (cross-linking pH, chitosan concentration, cross-linking
      time, molecular weight of chitosan, and drug concentration). Single-step
      formulation technique was compared with multi-step technique. Effect of these
      parameters was investigated on shape, size, weight, weight loss (WL), moisture
      content (MC), encapsulation efficiency (EE), drug loading (L), and drug release
      pattern of the microparticles. The formulation conditions were optimized from the
      drug release study. In vivo pharmacokinetics of the zinc-pectinate particles was
      compared with the zinc-pectin-chitosan composite particles in rats. Formulations
      were spherical with 920.48-1107.56 MUm size, 21.19-24.27 mg weight of 50
      particles, 89.83-94.34% WL, 8.31-13.25% MC, 96.95-98.85% EE, and 17.82-48.31% L.
      Formulation parameters showed significant influence on drug release pattern from
      the formulations. Formulation prepared at pH 1.5, 1% chitosan, 120 min cross
      linking time, and pectin:drug at 3:1 ratio demonstrated colon-specific drug
      release. Microparticles were stable at 4  degrees C and room temperature.
      Pharmacokinetic study indicated in vivo colon-specific drug release from the zinc
      pectin-chitosan composite particles only.

PMID- 21168476
TI  - Pain-related aversion induces astrocytic reaction and proinflammatory cytokine
      expression in the anterior cingulate cortex in rats.
AB  - Pain involves sensory and affective dimensions. It is well-known that activation
      of glial cells and a subsequent increase in proinflammatory cytokines contribute
      to the pathogenesis of pain sensation. However, the role of glial cells and
      proinflammatory cytokines in pain affect is unclear. Several lines of evidence
      indicate that the anterior cingulate cortex (ACC) is a key structure for pain
      affect. Using the formalin-induced conditioned place avoidance (F-CPA) model,
      which reflects the pain-related negative affective state induced by nociceptive
      stimuli, we examined the mRNA and protein expression levels of astrocytic markers
      and proinflammatory cytokines in the ACC. F-CPA produced robust aversion-like
      behaviors in rats. In parallel, a significant increase of mRNA of astrocytic
      markers (GFAP and S100B), and proinflammatory cytokines (IL-1beta and TNF-alpha)
      were observed in the ACC. The protein level of GFAP, IL-1beta and TNF-alpha were
      also enhanced in the ACC. The results showed for the first time that astrocytes
      and proinflammatory cytokines are associated with the processing of pain-related
      aversion and may be crucial players in the affective dimension of pain in rats.

PMID- 21168478
TI  - Serial MRI study of the enhanced therapeutic effects of liposome-encapsulated
      citicoline in cerebral ischemia.
AB  - Liposome encapsulation of active principles enhances their bioavailability to the
      brain. We investigated whether encapsulation of citicoline in liposomes increases
      its therapeutic effects in ischemia, performing a longitudinal MRI study of
      lesion volumes and edema in an animal model of stroke. Nineteen rats were
      submitted to permanent occlusion of the middle cerebral artery and treated with:
      (1) saline, (2) intraperitoneal citicoline (500mg/kg), (3) intravenous citicoline
      (48mg/kg), and (4) intravenous liposome-encapsulated citicoline (48mg/kg). Lesion
      volumes were measured by MRI at days 0, 1, 3 and 7 following surgery.
      Encapsulation in liposomes increased the therapeutic effects of citicoline, as
      reflected by a 32% reduction of the infarct sizes at day 7, in contrast with
      controls where infarct sizes at day 7 increased by 39%, respect to values at day
      0. Intravenously injected citicoline reduced infarct sizes by 9% while
      intraperitoneal citicoline resulted in an increase of infarct sizes by 10%. A
      slight (not significant) reduction of edema formation was observed for animals
      treated with citicoline, in all of its delivery forms. Liposome-encapsulated
      citicoline causes a noticeable reduction in lesion volumes as compared to free
      citicoline (either i.p. or i.v.) at days 1, 3 and 7 following permanent stroke.

PMID- 21168479
TI  - Relationship between gap detection thresholds and loudness in cochlear-implant
      users.
AB  - Gap detection threshold (GDT) is a commonly used measure of temporal acuity in
      cochlear-implant (CI) recipients. This measure, like other measures of temporal
      acuity, shows considerable variation across subjects and also varies across
      stimulation sites within subjects. The aims of this study were (1) to determine
      whether across-site variation in GDTs would be reduced or maintained with
      increased stimulation levels; (2) to determine whether across-site variation in
      GDTs at low stimulation levels was related to differences in loudness percepts at
      those same levels; and (3) to determine whether matching loudness levels could
      reduce across-site differences in GDTs. Thresholds and maximum comfortable
      loudness levels were measured in postlingually deaf adults using all available
      sites in their electrode arrays. All sites were then surveyed at 30% of the
      dynamic range (DR) to examine across-site variation. Two sites with the largest
      difference in GDTs were then selected and for those two sites GDTs were measured
      at multiple levels of the DR (10%, 30%, 50%, 70%, and 90%). Stimuli consisted of
      500 ms trains of symmetric-biphasic pulses, 40 MUs/phase, presented at a rate of
      1000 pps using a monopolar (MP1+2) electrode configuration. To examine perceptual
      differences in loudness, the selected sites were loudness-matched at the same
      levels of the DR. Variations in GDTs and loudness patterns were observed across
      stimulation sites and across subjects. Variations in GDTs across sites tended to
      decrease with increasing stimulation levels. For the majority of the subjects,
      stimuli at a given level in %DR were perceived louder at sites with better GDTs
      than those presented at the same level in %DR at sites with poorer GDTs. These
      results suggest that loudness is a contributing factor to across-site variation
      in GDTs and that CI fittings based on more detailed loudness matching could
      reduce across-site variation and improve perceptual acuity.

PMID- 21168480
TI  - The gut microbiota: a new player in the innate immune stress response?

PMID- 21168481
TI  - Atomic force microscopy analysis shows surface structure changes in carvacrol
      treated bacterial cells.
AB  - Carvacrol is a major component in some essential oils such as oregano and thyme
      and its inhibitory effect on the growth of various microorganisms is well
      documented. However, the active mechanism of carvacrol, as well as that of other
      essential oil components, has not yet been fully established and has generally
      not been well investigated. In this study, the antimicrobial activity of
      carvacrol against some Gram-positive and Gram-negative food-related bacterial
      strains was preliminarily verified and the effect of carvacrol on their cell
      envelope was further investigated by atomic force microscopy analysis. The atomic
      force microscopy images of the cells treated with carvacrol 3.3 mM for 1 h were
      analyzed by an appropriate software in order to visualize the effect of the
      treatment and to determine the values of cell surface roughness and some
      biometric parameters (cell length and width). The results showed that all
      microorganisms tested were sensitive to carvacrol both in solid and liquid media.
      Furthermore, images of cells of all strains treated with carvacrol exhibited
      appreciable modifications, indicating a change in cell surface structure.
      Finally, both length and diameter of the microorganisms decreased after contact
      with carvacrol.

PMID- 21168482
TI  - Molecular characterization of tissue-nonspecific alkaline phosphatase with an Ala
      to Thr substitution at position 116 associated with dominantly inherited
      hypophosphatasia.
AB  - Mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene are
      responsible for hypophosphatasia, an inborn error of bone and teeth metabolism
      associated with reduced levels of serum alkaline phosphatase activity. A missense
      mutation (c.346G>A) of TNSALP gene, which converts Ala to Thr at position 116
      (according to standardized nomenclature), was reported in dominantly transmitted
      hypophosphatasia patients (A.S. Lia-Baldini et al. Hum Genet. 109 (2001) 99-108).
      To investigate molecular phenotype of TNSALP (A116T), we expressed it in the COS
      1 cells or Tet-On CHO K1 cells. TNSALP (A116T) displayed not only negligible
      alkaline phosphatase activity, but also a weak dominant negative effect when co
      expressed with the wild-type enzyme. In contrast to TNSALP (W, wild-type), which
      was present mostly as a non-covalently assembled homodimeric form, TNSALP (A116T)
      was found to exist as a monomer and heterogeneously associated aggregates
      covalently linked via disulfide bonds. Interestingly, both the monomer and
      aggregate forms of TNSALP (A116T) gained access to the cell surface and were
      anchored to the cell membrane via glycosylphosphatidylinositol (GPI). Co
      expression of secretory forms of TNSALP (W) and TNSALP (A116T), which are
      engineered to replace the C-terminal GPI anchor with a tag sequence (his-tag or
      flag-tag), resulted in the release of heteromeric complexes consisting of TNSALP
      (W)-his and TNSALP (A116T)-flag. Taken together, these findings strongly suggest
      that TNSALP (A116T) fails to fold properly and forms disulfide-bonded aggregates,
      though it is indeed capable of interacting with the wild-type and reaching the
      cell surface, therefore explaining its dominant transmission.

PMID- 21168483
TI  - Metabolism of hyperforin, the active constituent of St. John's wort, in human
      liver microsomes.
AB  - The metabolism of hyperforin, one of the pharmacologically most active components
      of St. John's wort (Hypericum perforatum), was characterized in vitro using human
      liver microsomes and recombinant heterologously expressed P450 enzymes. A total
      of 57 hyperforin metabolites were detected. Of those, six were identified as
      monohydroxylations (M1-M6), while the others were formed via two or more
      hydroxylation reactions, via dehydrogenation, or by combinations of these
      reactions. A combined approach of cDNA-expressed recombinant CYPs, CYP-selective
      chemical inhibitors and correlation with CYP-specific marker activities indicated
      a central role of the CYP2C and CYP3A families in the metabolism of hyperforin.
      In addition, hyperforin was found to inhibit CYP2D6 and CYP3A4 model activities
      quite potently.

PMID- 21168484
TI  - A new PAT/QbD approach for the determination of blend homogeneity: combination of
      on-line NIRS analysis with PC Scores Distance Analysis (PC-SDA).
AB  - A novel and straightforward multivariate analytical tool for the qualitative
      determination of powder blend uniformity using on-line Near-Infrared Spectroscopy
      (NIRS) is presented. The approach combines current chemometric methods, e.g.
      spectral pre-processing and Principal Component Analysis (PCA), with (1) a new
      approach of data analysis to determine the end-point of the blending process, (2)
      building a design space (DS) for blend homogeneity and (3) developing a solid
      statistical rationale to stop blending according to Quality-by-Design (QbD)
      principles of FDA's Process Analytical Technology (PAT) initiative. The new
      approach comprises calculation of Euclidean distances between PCA scores in a
      multidimensional space and determination of Moving Block Standard Deviations
      (MBSDs) of successive Principal Component (PC) scores distances to estimate a
      time-window during blending where spectral variability decreases to a preset
      minimum. Hotelling's T(2) statistics is then used to monitor and report blend
      homogeneity. This technique is called "Principal Component Scores Distance
      Analysis" (PC-SDA). A Central Composite Design resulting in 10 batches mixed in a
      bin-blender (same composition, different blender fill level, different number of
      revolutions) was executed. NIR Chemical Imaging (NIR-CI) in combination with
      Symmetry Parameter Image Analysis (SPIA) was used to verify the NIRS analyzer
      response and assess homogeneity of all NIR-active components.

PMID- 21168485
TI  - Ultrasound active nanoscaled lipid formulations for thrombus lysis.
AB  - In the present study, we investigated the sonothrombolytic effect of new
      nanoscaled lipid formulations in human blood clots, using diagnostic ultrasound.
      Human blood clots of 1 ml were incubated with 1 MUl of the different lipid
      dispersions DPPC/CH, DPPC/PEG40S, DSPC/PEG40S and the commercially available
      ultrasound contrast agent SonoVue(r). Clots were stored for 3 days at 5  degrees
      C to obtain maximal clot retraction and lytic resistance. Each clot weight was
      determined before and after continuous insonation for 1h of insonation at 1.4
      MHz. The pressure in the insonation chamber was 80 mm Hg to mimic middle arterial
      blood pressure. There were no significant differences in thrombus weight before
      insonation. All nanoscaled formulations and SonoVue(r) were able to reduce
      thrombus weight compared to the weight loss of clots that were not insonated but
      kept under pressure for one hour (p < 0.001). We found a highly significant
      weight reduction with DSPC/PEG40S compared to SonoVue(r) (p = 0.007). Nanoscaled
      DSPC/PEG40S dispersion could be a promising formulation in ultrasound enhanced
      thrombolysis even without thrombolytic drugs. Stable cavitation is a crucial
      parameter in fragmentation of thrombus architecture. Further studies of
      physicochemical properties of DSPC/PEG40S are necessary to corroborate our
      hypothesis.

PMID- 21168486
TI  - Haloperidol-loaded polysorbate-coated polymeric nanocapsules increase its
      efficacy in the antipsychotic treatment in rats.
AB  - Haloperidol is an antipsychotic drug associated with the development of movement
      disorders. We evaluated the effect of its nanoencapsulation on its
      pharmacological activity and motor side effects. Haloperidol-loaded polysorbate
      coated nanocapsules (H-NC) showed nanometric size, negative zeta potential and
      low polydispersity indices and high encapsulation efficiency (>95%). Rats
      received a single dose of H-NC (0.2mg/kg ip) and four doses of D,L-amphetamine,
      AMPH (8.0mg/kg ip), injected every 3h (0, 3, 6 and 9h). The AMPH-induced
      stereotyped movements were quantified in the intervals of 15 min after each of
      four doses of AMPH, demonstrating greater pharmacological efficacy of the H-NC
      over free haloperidol (FH). The acute motor side effects were evaluated 1h after
      a single dose of H-NC or its free solution (0.2mg/kg ip). The group treated with
      H-NC presented lower extrapyramidal effects (catalepsy and oral dyskinesia) than
      those treated with FH. In the last experimental set, rats sub-chronically treated
      with a daily dose of H-NC (0.2mg/kg ip) for 28 days showed a lower incidence of
      extrapyramidal effects than those treated with the free drug (0.2mg/kg ip). Our
      findings showed the potential of using H-NC in the development of a nanomedicine
      aimed at increasing the efficacy of this antipsychotic drug and reducing its side
      effects.

PMID- 21168487
TI  - Ethylene vinyl acetate as matrix for oral sustained release dosage forms produced
      via hot-melt extrusion.
AB  - Different ethylene vinyl acetate grades (EVA9, EVA15, EVA28 and EVA40 having a VA
      content of 9%, 15%, 28% and 40%, respectively) were characterized via
      differential scanning calorimetry. Glass transition temperature (T(g)), polymer
      crystallinity, melting point and polymer flexibility were positively influenced
      by the vinyl acetate content. The processability of EVA-based formulations
      produced by means of hot-melt extrusion (2mm die) was evaluated in function of VA
      content, extrusion temperature (60-140 degrees C) and metoprolol tartrate (MPT,
      used as model drug) concentration (10-60%). Matrices containing 50% MPT resulted
      in smooth-surfaced extrudates, whereas at 60% drug content severe surface defects
      (shark skinning) were observed. Drug release from EVA/MPT matrices (50/50, w/w)
      was affected by the EVA grades: 90% after 24h for EVA15 and 28, while EVA9 and
      EVA40 formulations released 80% and 60%, respectively. Drug release also depended
      on drug loading and extrusion temperature. For all systems, the total matrix
      porosity (measured by X-ray tomography) was decreased after dissolution due to
      elastic rearrangement of the polymer. However, the largest porosity reduction was
      observed for EVA40 matrices as partial melting of the structure (melt onset
      temperature: 34.7 degrees C) also contributed (thereby reducing the drug release
      pathway and yielding the lowest release rate from EVA40 formulations). The
      Simulator of the Human Intestinal Microbial Ecosystem (SHIME) used to evaluate
      the stability of EVA during gastrointestinal transit showed that EVA was not
      modified during GI transit, nor did it affect the GI ecosystem following oral
      administration.

PMID- 21168488
TI  - Reversible targeting and controlled release delivery of daunorubicin to cancer
      cells by aptamer-wrapped carbon nanotubes.
AB  - AIM: Single-walled carbon nanotubes (SWNTs) have been already used as drug
      carriers. In this study, we introduced sgc8c aptamer (this aptamer targets
      leukemia biomarker protein tyrosine kinase-7) to complex between Dau
      (daunorubicin) and SWNT to enhance targeted delivery of Dau to acute
      lymphoblastic leukemia T-cells (Molt-4). MATERIAL AND METHODS: Dau-aptamer-SWNTs
      tertiary complex formation was analyzed by visible spectroscopy and
      spectrofluorophotometric analysis. Dau release profiles from the complex were
      investigated in pH 7.4 and 5.5. For cytotoxic studies (MTT assay), Molt-4
      (target) and U266 (B lymphocyte human myeloma, non-target) cells were treated
      with Dau, Dau-aptamer-SWNTs tertiary complex. Internalization was analyzed by
      flow cytometry. Targeted delivery of Dau was antagonized using antisense of
      aptamer. RESULTS: Dau was efficiently loaded onto SWNTs (efficiency ~ 157%). Dau
      was released from Dau-aptamer-SWNTs tertiary complex in a pH-dependent manner
      (higher release rate at pH 5.5). Flow cytometric analysis showed that the
      tertiary complex was internalized effectively to Molt-4 cells, but not to U266
      cells. Cytotoxicity of Dau-aptamer-SWNTs tertiary complex also confirmed
      internalization data. Dau-aptamer-SWNTs tertiary complex was less cytotoxic in
      U266 cells when compared to Dau alone. No significant change in viability between
      Dau- and complex-treated Molt-4 cells was observed. Cytotoxicity of Dau-aptamer
      SWNTs complex was efficiently and quickly reversed using antisense in Molt-4
      cells. CONCLUSION: Dau-aptamer-SWNTs complex is able to selectively target Molt-4
      cells. The other advantages of this system are reversibility and pH-dependent
      release of Dau from its complex.

PMID- 21168489
TI  - Online monitoring of dissolution tests using dedicated potentiometric sensors in
      biorelevant media.
AB  - The performance of the Ion-Selective Electrode (ISE) for in vitro dissolution
      testing using biorelevant media was evaluated in this study. In vitro dissolution
      was carried out using USP apparatus 2 (paddle method) with classical and with
      updated biorelevant media to simulate the pre- and postprandial states. The ISE
      was used as an analytical stand-alone system and in combination with a single
      point HPLC-UV measurement. A modified method enabling the use of the ISE for very
      poorly soluble substances is also proposed. In terms of f(2)-factor, the results
      acquired using the ISE for the drug diphenhydramine-HCl were found to be very
      similar to the results obtained by manual sampling followed by HPLC-UV analysis.
      In Fed State Simulated Gastric Fluid (FeSSGF), a medium containing 50% milk, the
      ISE is more practical since the need to separate proteins from the analyte prior
      to HPLC-UV analysis is eliminated. Further work will be needed to establish ISE
      methodology for Fed State Simulated Intestinal Fluid (FeSSIF) media. In summary,
      the ISE has promise as an analytical tool for research and development
      applications.

PMID- 21168490
TI  - A Quality by Design approach to investigate tablet dissolution shift upon
      accelerated stability by multivariate methods.
AB  - This paper presents the use of experimental design, optimization and multivariate
      techniques to investigate root-cause of tablet dissolution shift (slow-down) upon
      stability and develop control strategies for a drug product during formulation
      and process development. The effectiveness and usefulness of these methodologies
      were demonstrated through two application examples. In both applications,
      dissolution slow-down was observed during a 4-week accelerated stability test
      under 51 degrees C/75%RH storage condition. In Application I, an experimental
      design was carried out to evaluate the interactions and effects of the design
      factors on critical quality attribute (CQA) of dissolution upon stability. The
      design space was studied by design of experiment (DOE) and multivariate analysis
      to ensure desired dissolution profile and minimal dissolution shift upon
      stability. Multivariate techniques, such as multi-way principal component
      analysis (MPCA) of the entire dissolution profiles upon stability, were performed
      to reveal batch relationships and to evaluate the impact of design factors on
      dissolution. In Application II, an experiment was conducted to study the impact
      of varying tablet breaking force on dissolution upon stability utilizing MPCA. It
      was demonstrated that the use of multivariate methods, defined as Quality by
      Design (QbD) principles and tools in ICH-Q8 guidance, provides an effective means
      to achieve a greater understanding of tablet dissolution upon stability.

PMID- 21168491
TI  - The influence of crystallization inhibition of HPMC and HPMCAS on model substance
      dissolution and release in swellable matrix tablets.
AB  - One of the drawbacks with solid solution systems is their thermodynamic
      instability in solution. Considering the release of these systems from extended
      release formulations, in particular swellable matrix tablets, a successful tablet
      formulation can be regarded as a composition able to maintain the molecular state
      of the poorly soluble crystalline drug through diffusion in the matrix. This may
      in turn provide molecular rather than particulate delivery of the substance from
      the matrix. In this study, the solid state and dissolution behavior of amorphous
      solid dispersions of a model crystalline substance, butyl paraben in HPMC and
      HPMCAS, was investigated. In addition, the suitability of HPMCAS as both
      effective solid solution carrier and as extended-release matrix forming polymer
      was examined. The release from all systems investigated showed extended-release
      capacity with a release rate similar to the rate of matrix erosion. However, a
      detailed study of the factors affecting the release mechanism revealed that upon
      hydration, the model substance crystallized in the gel layer of the HPMC-based
      formulation, whereas it remained in amorphous form in the HPMCAS tablets. In the
      case of HPMCAS formulation, this effect was attributed to (i) the ability of this
      polymer to keep the model substance in a supersaturated state and (ii) the very
      slow matrix hydration, resulting in a steep concentration gradient of the drug
      substance and a short diffusion path through the matrix into the dissolution
      bulk.

PMID- 21168492
TI  - Metformin promotes progesterone receptor expression via inhibition of mammalian
      target of rapamycin (mTOR) in endometrial cancer cells.
AB  - Progesterone has been used in the hormonal treatment of endometrial cancer (EC)
      for many years, but the response rates are unsatisfying. The down-regulated
      progesterone receptor (PR) is the main reason for treatment failure. The insulin
      like growth factor (IGF) system is related to EC risk, and IGF-I can inhibit PR
      transcription in breast cancer. Recent evidence suggests that metformin-combined
      oral contraceptives may reverse progesterone-resistant atypical endometrial
      hyperplasia, but the mechanism is unclear. We attempt to investigate the
      interaction of metformin, PR and IGF-II expression, and identify whether
      metformin can enhance the antitumor effect of medroxyprogesterone acetate (MPA)
      using Ishikawa and HEC-1B EC cell lines. We found that both IGF-I and IGF-II
      inhibit PR A/B mRNA and protein expression, whereas metformin markedly promotes
      PR expression. In parallel, IGF-II increases phosphorylation of AKT and p70S6K,
      while metformin increases AMPK phosphorylation and decreases p70S6K
      phosphorylation. The effects of metformin on PR A/B and p70S6K are partially
      reversed by an AMPK inhibitor. Furthermore, metformin synergistically
      antiproliferates MPA in two cell lines, with the peak synergy occurring with
      10MUM metformin combined with 1MUM MPA (CI=0.20448 for Ishikawa, CI=0.12801 for
      HEC-1B). Our results demonstrate that metformin promotes PR expression, which can
      be inhibited by overexpressed IGF-II in EC. This effect is partially mediated
      through activating AMPK followed by inhibiting the overactivated mTOR pathway.

PMID- 21168494
TI  - Abnormal plasticity in dystonia: Disruption of synaptic homeostasis.
AB  - Work over the past two decades lead to substantial changes in our understanding
      of dystonia, which was, until recently, considered an exclusively sporadic
      movement disorder. The discovery of several gene mutations responsible for many
      inherited forms of dystonia has prompted much effort in the generation of
      transgenic mouse models bearing mutations found in patients. The large majority
      of these rodent models do not exhibit overt phenotypic abnormalities, or neuronal
      loss in specific brain areas. Nevertheless, both subtle motor abnormalities and
      significant alterations of synaptic plasticity have been recorded in mice,
      suggestive of an altered basal ganglia circuitry. In addition, robust evidence
      from experimental and clinical work supports the assumption that dystonia may
      indeed be considered a disorder linked to the disruption of synaptic "scaling",
      with a prevailing facilitation of synaptic potentiation, together with the loss
      of synaptic inhibitory processes. Notably, neurophysiological studies from
      patients carrying gene mutations as well as from non-manifesting carriers have
      shown the presence of synaptic plasticity abnormalities, indicating the presence
      of specific endophenotypic traits in carriers of the gene mutation. In this
      survey, we review findings from a broad range of data, obtained both from animal
      models and human research, and propose that the abnormalities of synaptic
      plasticity described in mice and humans may be considered an endophenotype to
      dystonia, and a valid and powerful tool to investigate the pathogenic mechanisms
      underlying this movement disorder. This article is part of a Special Issue
      entitled "Advances in dystonia".

PMID- 21168493
TI  - Molecular targets that link dioxin exposure to toxicity phenotypes.
AB  - Many toxicology studies have elucidated health effects associated with exposure
      to various chemicals, but few have identified the molecular targets that cause
      specific endpoints of toxicity. Our understanding of the toxicity of dioxins, a
      group of chemicals capable of causing toxicity at environmentally relevant levels
      of exposure, is no exception. Dioxins are unique compared to most chemicals that
      we are exposed to in the environment because they activate a high affinity
      receptor, aryl hydrocarbon receptor (AhR), that was identified more than three
      decades ago. In recent years, several lines of experimental evidence have
      provided clues for opening the "black box" that contains the molecular mechanisms
      of dioxin action. These clues have emerged by toxicologists beginning to identify
      the molecular targets that link AhR signaling to tissue-specific toxicity
      phenotypes. Endpoints of dioxin toxicity for which downstream molecular targets
      have begun to be elucidated are observed in developmental or tissue regeneration
      processes, and include impaired prostate development and hydronephrosis in mouse
      fetuses and pups, reduced midbrain blood flow and jaw malformation in zebrafish
      embryos, and impaired fin regeneration in larval and adult zebrafish. Significant
      progress in identifying molecular targets for dioxin-induced hepatotoxicity in
      adult mice also has occurred. Misregulation of AhR downstream pathways, such as
      conversion of arachidonic acid to prostanoids via cyclooxygenase-2, and altered
      Wnt/beta-catenin signaling downregulating Sox9, and signaling by receptors for
      inflammatory cytokines have been implicated in tissue-specific endpoints of
      dioxin toxicity. These findings may not only begin to clarify the molecular
      targets of dioxin action but shed light on new molecular events associated with
      development and disease.

PMID- 21168495
TI  - CD47 knockout mice exhibit improved recovery from spinal cord injury.
AB  - Recent data have implicated thrombospondin-1 (TSP-1) signaling in the acute
      neuropathological events that occur in microvascular endothelial cells (ECs)
      following spinal cord injury (SCI) (Benton et al., 2008b). We hypothesized that
      deletion of TSP-1 or its receptor CD47 would reduce these pathological events
      following SCI. CD47 is expressed in a variety of tissues, including vascular ECs
      and neutrophils. CD47 binds to TSP-1 and inhibits angiogenesis. CD47 also binds
      to the signal regulatory protein (SIRP)alpha and facilitates neutrophil
      diapedesis across ECs to sites of injury. After contusive SCI, TSP-1(-/-) mice
      did not show functional improvement compared to wildtype (WT) mice. CD47(-/-)
      mice, however, exhibited functional locomotor improvements and greater white
      matter sparing. Whereas targeted deletion of either CD47 or TSP-1 improved acute
      epicenter vascularity in contused mice, only CD47 deletion reduced neutrophil
      diapedesis and increased microvascular perfusion. An ex vivo model of the CNS
      microvasculature revealed that CD47(-/-)-derived microvessels (MVs) prominently
      exhibit adherent WT or CD47(-/-) neutrophils on the endothelial lumen, whereas WT
      derived MVs do not. This implicates a defect in diapedesis mediated by the loss
      of CD47 expression on ECs. In vitro transmigration assays confirmed the role of
      SIRPalpha in neutrophil diapedesis through EC monolayers. We conclude that CD47
      deletion modestly, but significantly, improves functional recovery from SCI via
      an increase in vascular patency and a reduction of SIRPalpha-mediated neutrophil
      diapedesis, rather than the abrogation of TSP-1-mediated anti-angiogenic
      signaling.

PMID- 21168496
TI  - Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice.
AB  - The generation and maturation of adult neural stem/progenitor cells are impaired
      in many neurodegenerative diseases, among them is Parkinson's disease (PD). In
      mammals, including humans, adult neurogenesis is a lifelong feature of cellular
      brain plasticity in the hippocampal dentate gyrus (DG) and in the subventricular
      zone (SVZ)/olfactory bulb system. Hyposmia, depression, and anxiety are early non
      motor symptoms in PD. There are parallels between brain regions associated with
      non-motor symptoms in PD and neurogenic regions. In autosomal dominant PD,
      mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are frequent. LRRK2
      homologs in non-vertebrate systems play an important role in chemotaxis, cell
      polarity, and neurite arborization. We investigated adult neurogenesis and the
      neurite development of new neurons in the DG and SVZ/olfactory bulb system in
      bacterial artificial chromosome (BAC) human Lrrk2 G2019S transgenic mice. We
      report that mutant human Lrrk2 is highly expressed in the hippocampus in the DG
      and the SVZ of adult Lrrk2 G2019S mice. Proliferation of newly generated cells is
      significantly decreased and survival of newly generated neurons in the DG and
      olfactory bulb is also severely impaired. In addition, after stereotactic
      injection of a GFP retrovirus, newly generated neurons in the DG of Lrrk2 G2019S
      mice exhibited reduced dendritic arborization and fewer spines. This loss in
      mature, developed spines might point towards a decrease in synaptic connectivity.
      Interestingly, physical activity partially reverses the decrease in neuroblasts
      observed in Lrrk2 G2010S mice. These data further support a role for Lrrk2 in
      neuronal morphogenesis and provide new insights into the role of Lrrk2 in adult
      neurogenesis.

PMID- 21168497
TI  - Efficiency of laryngeal motor nerve repair is greater with bulbar than with
      mucosal olfactory ensheathing cells.
AB  - The real ability of OECs provided by olfactory mucosa cultures (OM-OECs) and
      those from olfactory bulb cultures (OB-OECs) must be better characterized in
      order to propose their future clinical application. Therefore, we used a lesion
      of the vagus nerve (VN), which constitutes a severe motor denervation due to long
      distance of the muscular targets (4.5 cm). We performed a section/anastomosis
      surgery of the VN, at the third tracheal ring. Then, OM-OECs and OB-OECs were
      injected in matrigel around the lesion site. Three months after surgery,
      laryngeal muscle activity, synkinesis phenomena and latency were evaluated by
      videolaryngoscopy and electromyography recordings. To complete these procedures,
      axonal morphometric study of the right recurrent nerve was performed to assess
      axonal regrowth and tracking of green fluorescent protein positive cells was
      performed. Recurrent nerve is the motor branch innervating the laryngeal muscles,
      and is located distally to the lesion, near the muscular targets (0.7 cm). These
      analyses permitted to compare the ability of these two populations to improve
      functional recovery and axonal regrowth. Our results show that, OM-OECs improved
      electrical muscular activity and nervous conduction with significant tissue
      healing but induced aberrant movement and poor functional recovery. In contrast,
      OB-OECs induced a partial functional recovery associated with an increase in the
      number of myelinated fibers and nervous conduction. Our study suggests that, as
      recently reported in a microarray study, OM-OECs and OB-OECs express different
      properties. In particular, OM-OECs could regulate inflammation processes and
      extracellular matrix formation but have a poor regeneration potential, whereas,
      OB-OECs could improve functional recovery by inducing targeted axonal regrowth.

PMID- 21168498
TI  - Evidence of endoplasmic reticular stress in the spinal motor neurons exposed to
      CSF from sporadic amyotrophic lateral sclerosis patients.
AB  - We have earlier reported that intrathecal injection of cerebrospinal fluid (CSF)
      from sporadic Amyotrophic Lateral Sclerosis patients (ALS-CSF) into neonatal rats
      and supplementation of rat spinal cord cultures with ALS-CSF induces motor neuron
      degeneration via aberrant neurofilament phosphorylation and Golgi apparatus
      fragmentation. Intracellular aggregates immunoreactive to ubiquitin,
      phosphorylated neurofilaments and choline acetyl transferase (ChAT) were
      prominently seen in NSC-34 cells exposed to ALS-CSF. Protein aggregation could
      cause stress on endoplasmic reticulum (ER) and may precede Golgi fragmentation.
      Here we assessed the effect of ALS-CSF on the expression of GRP-78 and caspase-12
      proteins, the markers of ER stress responses, in NSC-34 cells and rat spinal
      cords by immunochemistry and immunoblotting. Both in vitro and in vivo, increased
      expression of these proteins accompanied elevated active caspase-12 levels.
      Apoptotic nuclei and nuclear translocation of caspase-12 were noted in some
      cells. In vitro, the occurrence of ER stress was supported by electron
      microscopic observations of numerous free polyribosomes and fragmented ER
      cisternae. Aggregated mSOD1 protein causes ER stress in familial ALS. ER stress
      is also reported in the autopsy samples of sporadic ALS. Thus our observation of
      ER stress may be linked to the protein aggregation, viz. phosphorylated
      neurofilaments and ChAT, reported earlier.

PMID- 21168500
TI  - Mesenchymal stem cell transplantation modulates neuroinflammation in focal
      cerebral ischemia: contribution of fractalkine and IL-5.
AB  - Mesenchymal stem cells (MSCs) are reported to possess immunomodulatory
      properties. Previous reports have demonstrated the beneficial effects of MSC
      transplantation in focal cerebral ischemia animal models. In this study, we have
      investigated the neuroimmunomodulatory functions of human MSCs, transplanted in a
      rat focal ischemia model of transient middle cerebral artery occlusion (MCAO).
      Our results revealed that in a human mesenchymal stem cell line, B10 cell
      transplantation decreased the accumulation of Iba-1(+) microglia and GFAP(+)
      astrocytes, and inhibited proinflammatory gene expression in the core and
      ischemic border zone (IBZ). Among the proinflammatory genes iNOS, which was
      expressed in microglia/macrophage, was persistently inhibited up to 7days after
      MCAO. In vivo laser capture microdissection and double immunofluorescence
      staining, and in vitro B10 cell culture experiments showed that, in inflammatory
      conditions, B10 cells expressed cytokines and growth factors including IL-5,
      fractalkine, IGF-1, GDNF and VEGF. Fractalkine and IL-5 inhibited cytokine
      induced proinflammatory gene expression including iNOS in a human microglia cell
      line. Thus, our results demonstrate that MSC transplantation suppresses MCAO
      focal ischemia-induced inflammation, possibly through expression of fractalkine
      and IL-5.

PMID- 21168501
TI  - The Wlds transgene reduces axon loss in a Charcot-Marie-Tooth disease 1A rat
      model and nicotinamide delays post-traumatic axonal degeneration.
AB  - Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy and a
      duplication of the peripheral myelin protein of 22 kDa (PMP22) gene causes the
      most frequent subform CMT1A. Clinical impairments are determined by the amount of
      axonal loss. Axons of the spontaneous mouse mutant Wallerian degeneration slow
      (Wlds) show markedly reduced degeneration following various types of injuries.
      Protection is conferred by a chimeric Wlds gene encoding an N-terminal part of
      ubiquitination factor Ube4b and full length nicotinamide mononucleotide adenylyl
      transferase 1 (Nmnat1). Nmnat1 enzyme generates nicotinamide adenine dinucleotide
      (NAD) from nicotinamide mononucleotide. Here, in a Pmp22 transgenic animal model
      of Charcot-Marie-Tooth disease type 1A (CMT rat), the Wlds transgene reduced
      axonal loss and clinical impairments without altering demyelination. Furthermore,
      nicotinamide - substrate precursor of the Nmnat1 enzyme - transiently delayed
      posttraumatic axonal degeneration in an in vivo model of acute peripheral nerve
      injury, but to a lower extent than Wlds. In contrast, 8 weeks of nicotinamide
      treatment did not influence axonal loss or clinical manifestations in the CMT
      rat. Therefore, nicotinamide can partially substitute for the protective Wlds
      effect in acute traumatic, but not in chronic secondary axonal injury. Future
      studies are needed to develop axon protective therapy in CMT1A which may be
      combined with therapeutic strategies aimed at downregulation of toxic PMP22
      overexpression.

PMID- 21168499
TI  - Genetic and clinical features of primary torsion dystonia.
AB  - Primary torsion dystonia (PTD) is defined as a syndrome in which dystonia is the
      only clinical sign (except for tremor), and there is no evidence of neuronal
      degeneration or an acquired cause by history or routine laboratory assessment.
      Seven different loci have been recognized for PTD but only two of the genes have
      been identified. In this review we will describe the phenotypes associated with
      these loci and discuss the responsible gene. This article is part of a Special
      Issue entitled "Advances in dystonia".

PMID- 21168502
TI  - Inhibition of lactic dehydrogenase as a way to increase the anti-proliferative
      effect of multi-targeted kinase inhibitors.
AB  - Protein kinase inhibitors are a relatively new class of promising anticancer
      drugs, most of which exert their action by binding to the ATP site on the
      targeted kinases. We hypothesized that a decrease in ATP levels in neoplastic
      cells could reduce the competition for the same enzymatic site, thus increasing
      the efficacy of kinase inhibitors. Using oxamic acid, an inhibitor of lactic
      dehydrogenase (LDH) which hinders aerobic glycolysis, we decreased ATP levels in
      PLC/PRF/5 cells (a line from a hepatocellular carcinoma). We found that in these
      cells oxamic acid potentiated the antiproliferative activity of sorafenib,
      imatinib and sunitinib, three kinase inhibitors. When aerobic glycolysis was shut
      down by culturing the cells in the absence of glucose, oxamic acid did not reduce
      the ATP levels, suggesting that in normal tissues, which do not rely on aerobic
      glycolysis for their ATP synthesis, the block of LDH should not impair cellular
      metabolism. In conclusion, the inhibition of LDH could enhance anticancer
      activity of sorafenib, imatinib and sunitinib without increasing their side
      effects on normal cells, which in conditions of normal functional activity and
      sufficient oxygen supply do not need the activity of this enzyme.

PMID- 21168503
TI  - Berberine possesses muscarinic agonist-like properties in cultured rodent
      cardiomyocytes.
AB  - Berberine, a natural product alkaloid, has been shown to display a wide array of
      pharmacological effects. Generally, the mechanism of action of each of these
      effects has not been well described. The aim of the present study is to test the
      hypothesis that some of berberine's cardiovascular effects are mediated through
      activation of cardiac M2 muscarinic cholinergic receptors. In our studies, we
      tested the ability of berberine to alter the contraction rate of cultured
      neonatal rodent cardiomyocytes. In these spontaneously contracting primary
      cultured cells, berberine reduced the contraction rate in a manner independent of
      beta-adrenergic receptor blockade but sensitive to pertussis toxin, a Gi/o G
      protein inhibitor. Muscarinic antagonists completely blocked the effect of
      berberine on contraction rate of cardiomyocytes, whereas the effect of berberine
      was not opposed by antagonists to opioid, adenosine or alpha-adrenergic
      receptors. Further, berberine bound to muscarinic receptors of adult mouse heart
      membranes with relatively high affinity (K(i)=5.4*10(-6)M) comparable to that of
      the classic muscarinic agonist, carbachol, and to muscarinic M2 receptors
      exogenously expressed in HEK 293 cells (K(i)=4.9*10(-6)M). Therefore, the
      findings of the present study suggest that berberine is a muscarinic agonist at
      M2 receptors, potentially explaining some of its reported cardiovascular effects.

PMID- 21168505
TI  - Model based optimization of the fed-batch production of a highly active
      transglutaminase variant in Escherichia coli.
AB  - A process for the production of a thermostable variant of a microbial
      transglutaminase was developed. The transglutaminase variant produced, carried a
      single amino acid exchange (serine replaced by proline at position 2) and showed
      a nearly doubled specific activity of 46.1 Umg(-1) compared to the wild-type
      enzyme. Based on a model based optimization strategy, intracellular soluble
      production in Escherichia coli was optimized. After parameter identification and
      only two fed-batch cultivations, a space time yield of 1438 U(TG)L(-1)h(-1) was
      obtained which is 175% higher than the highest values published so far
      (extracellular production using Corynebacterium ammoniagenes). High carbon source
      concentrations during expression were found to increase the product formation.
      Prior to the fed-batch cultivation, the host strain was adapted from complex
      medium to minimal medium by serial dilution. Upon transfer to the minimal medium,
      initially the maximal growth rate dropped to 0.13 h(-1). After the six
      consecutive cultivations the rate increased to 0.47 h(-1) and the portion of the
      complex medium was reduced to 1 ppm. Using the adapted cells, temperature after
      induction and IPTG-concentration were investigated by satellite batch cultivation
      according to a Design of Experiment (DoE) plan. The product yield was strongly
      influenced by the temperature after induction but not by the inductor
      concentration. The highest specific activity of 1386 Ug(-1) bio dry mass was
      obtained at 29 degrees C and 0.7 mM IPTG.

PMID- 21168506
TI  - FhuA deletion variant Delta1-159 overexpression in inclusion bodies and refolding
      with Polyethylene-Poly(ethylene glycol) diblock copolymer.
AB  - Membrane protein isolation is a challenging problem. In fact especially their
      extraction from the respective membrane is difficult and often goes along with
      losses in yield. Usually expensive detergents are needed to extract the target
      protein from the membrane. Therefore finding an efficient overexpression and
      extraction method and an alternative to detergents is desirable. In this study we
      describe a new and fast method to express, extract and purify an engineered
      variant of the FhuA protein (FhuA Delta1-159) that acts as passive diffusion
      channel, using a diblock copolymer as an alternative to detergents like octyl-POE
      (n-octylpolyoxyethylene). The N-terminal leader sequence, facilitating the
      protein's transport to the outer membrane was deleted (FhuA Delta1-159
      Deltasignal), resulting in protein accumulation in easy to isolate inclusion
      bodies. Urea was used to solubilise the unfolded protein and dialysis against
      phosphate-buffer containing the commercially available diblock copolymer PE
      PEG[Polyethylene-Poly(ethyleneglycol)] lead to protein refolding. Circular
      dichroism spectroscopy revealed a high beta-sheet percentage within the refolded
      protein secondary structure indicating the successful reconstitution of FhuA
      Delta1-159 Deltasignal native state. Furthermore the channel functionality of
      FhuA Delta1-159 Deltasignal was verified by measuring the in and out-flux through
      the protein when inserted into liposome membrane, using the HRP/TMB (HRP=Horse
      Radish Peroxidase, TMB=3,3',5,5'-tetramethylbenzidine) assay system.

PMID- 21168507
TI  - 2-DE proteomic analysis of HSP70 in mollusc Chamelea gallina.
AB  - Bidimensional electrophoresis (2-DE) protocols were adapted on Chamelea gallina
      digestive glands studies by the analysis of Heat Shock Proteins (HSP) compared
      with monodimensional electrophoresis (1-DE) results. Because polycyclic aromatic
      hydrocarbons (PAH) act on HSPs, C. gallina specimens were exposed to 0.5 mg/L of
      benzo[a]pyrene (B[a]P) for 24 h, 7 and 12 days. Immunoblotting after 1-DE showed
      a single band of 70 kDa significantly induced after 7 days of B[a]P exposure.
      After 2-DE, eight major high-resolved spots between 17 and 98 kDa were revealed.
      Three spots fell within the range of 62-98 kDa and of 5-6 pI, parameters which
      could include HSP70. Two spots of 77 and 72 kDa, obtained after 2-DE
      immunoblotting, could correspond to constitutive HSC70 and to inducible HSP70
      forms respectively. Changes observed in inducible and in constitutive forms might
      be related to an adaptation to stress and to a normal protein synthesis
      capability, respectively. Employment of 2-DE and relationship between HSP70 and
      HSC70 may be useful to clarify their role in molluscs subjected to stress events.

PMID- 21168508
TI  - Differential expression pattern of pituitary adenylate cyclase-activating
      polypeptide (PACAP) alternative splicing variants and its receptors in the immune
      system of rainbow trout (Oncorhynchus mykiss).
AB  - There are different studies concerning the immune functions of pituitary
      adenylate cyclase-activating polypeptide (PACAP), however information of its
      source in lymphoid organs is still scarce. Although the occurrence of the PACAP
      receptors PAC1, VPAC1 and VPAC2 in the immune system of mammals is known, only
      limited studies have reported the presence of some of these receptors in lymphoid
      organs in fish. In this work, we have studied both the expression of the two
      PACAP transcriptional variants (PRP/PACAP and PACAP) together with their
      receptors in diverse lymphoid organs of the rainbow trout (Oncorhynchus mykiss).
      Our results demonstrate for the first time in fish the presence of both
      transcripts in spleen, in which immunohistochemistry confirmed the production of
      PACAP by lymphocyte-like cells. In contrast, PACAP but not PRP/PACAP mRNA was
      detected in gills. Additionally, we observed a differential expression pattern of
      the PAC1, the PACAP specific receptor, with respect to VPAC1 and VPAC2 in
      lymphoid organs of fish. All receptors were detected in brain, intestine and
      spleen. By contrast, PAC1 and VPAC1 receptors but not VPAC2 were found in
      peripheral blood and in RTS11 rainbow trout monocyte/macrophage cells. Besides,
      in gills and skin, PAC1 and VPAC2 but not VPAC1 were observed, whereas in head
      kidney, the PAC1 receptor was the only one detected. In general, our finding
      added PACAP and its receptors to the list of neuroendocrine molecules present in
      the fish immune system, suggesting a direct autocrine/paracrine mechanism of
      PACAP action to mediate immune function in fish.

PMID- 21168504
TI  - Metastasis suppressors and the tumor microenvironment.
AB  - The most lethal and debilitating attribute of cancer cells is their ability to
      metastasize. Throughout the process of metastasis, tumor cells interact with
      other tumor cells, host cells and a variety of molecules. Tumor cells are also
      faced with a number of insults, such as hemodynamic sheer pressure and immune
      selection. This brief review explores how metastasis suppressor proteins regulate
      interactions between tumor cells and the microenvironments in which tumor cells
      find themselves.

PMID- 21168509
TI  - Intestinal T cells of Dicentrarchus labrax (L.): gene expression and functional
      studies.
AB  - Cellular and molecular data have evidenced a gut-associated lymphoid tissue in a
      variety of teleost species, abundantly containing T cells, whose origin,
      selection and functions are still unclear. This study reports CD4, CD8-alpha,
      MHCI-alpha, MHCII-beta, rag-1 and TCR-beta gene transcription along the intestine
      (anterior, middle and posterior segments) and in the thymus of one year-old
      Dicentrarchus labrax (L.). Real-time PCR findings depicted a main role of the
      thymus in T-cell development, but also rag-1 and CD8-alpha transcripts are
      detected in the intestine, having significant expression in the posterior
      segment. In the whole intestine TCR-beta and CD8-alpha exceeded CD4 transcripts.
      RNA ISH confirmed these data and detailed that mucosal CD8-alpha+ cells were
      especially numerous in the epithelium and in aggregates in the lamina propria.
      Regional differences in T-cell-specific gene expressions are first described in
      the intestine of a bony fish. High non-specific cytotoxic activity against
      xenogeneic and allogeneic cells was found in lymphocytes purified from the
      intestinal mucosa, providing further insight into their local defence roles.

PMID- 21168510
TI  - Three isoforms of anti-lipopolysaccharide factor identified from eyestalk cDNA
      library of swimming crab Portunus trituberculatus.
AB  - Anti-lipopolysaccharide factors (ALFs), as the potent antimicrobial peptides, can
      bind and neutralize lipopolysaccharide (LPS) and exhibit broad spectrum
      antimicrobial activities. In this study, three isoforms of the ALF homologues
      (PtesALF1-3) were identified from eyestalk cDNA library of swimming crab Portunus
      trituberculatus. The full-length cDNA sequences of PtesALF1, 2 and 3 were 1138,
      1052 and 1057 bp encoding 92, 108 and 123 amino acids, respectively. PtesALF1-3
      contained two conserved cysteine residues and shared high similarity with other
      reported ALFs. Predicted tertiary structures of PtesALF2 and 3 containing four
      beta-strands and three alpha-helix were similar to that described in Limulus
      polyphemus, while PtesALF1 had only one alpha-helix in its spatial structure.
      Sequence analysis revealed PtesALF1-3 were encoded by the same genomic locus and
      generated by alternative splicing of the pre-mRNA. Totally 89 SNPs including 18
      in coding region and 71 in noncoding region were detected by direct sequencing of
      30 genomic samples. The mRNA expression of PtesALF1 and PtesALF1-3 transcripts
      was mainly detected in haemocytes but showed different expression pattern in
      other tissues including hepatopancreas, gill, eyestalk and muscle. After
      challenge with Vibrio alginolyticus, the temporal expression level of PtesALF1-3
      transcripts in haemocytes showed a clear time-dependent response expression
      pattern with two peaks within the experimental period of 32 h, while PtesALF1 was
      up-regulated only once with obvious decrease at 6 h and significant increase at
      24 h. These results suggest that the PtesALF isoforms have different tissue
      specificity and might provide multiple protective functions against invading
      bacteria in P. trituberculatus.

PMID- 21168511
TI  - Visualization of nonlinear kernel models in neuroimaging by sensitivity maps.
AB  - There is significant current interest in decoding mental states from neuroimages.
      In this context kernel methods, e.g., support vector machines (SVM) are
      frequently adopted to learn statistical relations between patterns of brain
      activation and experimental conditions. In this paper we focus on visualization
      of such nonlinear kernel models. Specifically, we investigate the sensitivity map
      as a technique for generation of global summary maps of kernel classification
      models. We illustrate the performance of the sensitivity map on functional
      magnetic resonance (fMRI) data based on visual stimuli. We show that the
      performance of linear models is reduced for certain scan
      labelings/categorizations in this data set, while the nonlinear models provide
      more flexibility. We show that the sensitivity map can be used to visualize
      nonlinear versions of kernel logistic regression, the kernel Fisher discriminant,
      and the SVM, and conclude that the sensitivity map is a versatile and
      computationally efficient tool for visualization of nonlinear kernel models in
      neuroimaging.

PMID- 21168512
TI  - Left TPJ activity in verbal working memory: implications for storage- and sensory
      specific models of short term memory.
AB  - Patients with damage to the left temporoparietal junction (TPJ) have a low verbal
      span without concomitant deficits in speech perception. This pattern of cognitive
      impairment is taken as evidence for a dedicated phonological buffer that plays
      little role in perception (storage-specific account). In contrast, other research
      suggests that items are maintained and perceived in the same regions (sensory
      specific account). In an fMRI study, we demonstrate that the left TPJ does not
      respond in a way predicted of a phonological buffer; that is, activity in this
      region is not sustained during encoding or maintenance. Instead, a region in the
      superior temporal gyrus that has been associated with both speech perception and
      production demonstrated the expected profile of a store: it was more active in
      the verbal condition than the object condition and was active during both
      encoding and maintenance. These results support the sensory-specific account of
      short term memory rather than the storage-specific account. Based on the pattern
      of activity in the left TPJ, we suggest that the impairment of verbal working
      memory observed in patients with TPJ damage may be due to diminished attentional
      processes rather than reduced storage capacity.

PMID- 21168513
TI  - A hedonically complex odor mixture produces an attentional capture effect in the
      brain.
AB  - A counter-intuitive property of many pleasant and attractive stimuli is that they
      are hedonically complex, containing both pleasant and unpleasant components. A
      striking example is the floral scent of natural jasmine, which may contain more
      than 6% of indole, a pure chemical which is usually rated as unpleasant. Using
      fMRI we investigate the hypothesis that the interaction between the pleasant and
      unpleasant components in the hedonically complex natural jasmine produces an
      attentional capture effect in the brain. First, to localize brain areas involved
      in selective attention to odor, we compared neural activity in response to
      jasmine without indole when participants explicitly and selectively attended to
      either its pleasantness or intensity, with neural activity when no selective
      attention was required. We then show that the superior frontal gyrus has
      increased activity both when selective attention is being paid to jasmine without
      indole, and also when no selective attention is required but an unpleasant
      component is added to it to produce a hedonically complex mixture. The
      attentional capture effect in the superior frontal gyrus by the mixture was
      related to the hedonic complexity of the mixture across subjects; could not be
      explained by salience, intensity, or pleasantness; and was specific to the
      superior frontal gyrus in that it was not found in other prefrontal areas
      activated by selective attention. The investigation supports the new hypothesis
      that the affective potency of stimuli with mixed pleasant and unpleasant
      components is related at least in part to the recruitment of mechanisms in the
      brain involved in attentional capture and enhancement.

PMID- 21168514
TI  - Detection of hemodynamic responses to epileptic activity using simultaneous
      Electro-EncephaloGraphy (EEG)/Near Infra Red Spectroscopy (NIRS) acquisitions.
AB  - Simultaneous recordings of Electro-EncephaloGraphy (EEG) with Near InfraRed
      Spectroscopy (NIRS) allow measuring hemodynamic changes (changes in the
      concentration of oxy- and deoxyhemoglobin) at the time of epileptic discharges
      detected on scalp EEG. Two NIRS detection methods based on the General Linear
      Model (GLM) respectively in the time domain and in the time-frequency domain are
      investigated in this study using realistic simulations of spontaneous interictal
      epileptic activity. We evaluated the sensitivity at different Signal to Noise
      Ratios (SNR), the effect of either a large or a small number of discharges and
      the impact of model misspecification (e.g. omission or false detection of
      epileptic discharges). We also explored the effect on the estimation of key
      parameters, which set the model order. Simulations showed that both methods
      become inaccurate in lower SNR conditions, leading to many false positive
      detections. However, the time-frequency estimator showed better performance than
      the time-domain one. Key parameters for each algorithm were identified and
      results suggest to model confounds in the GLM differently for oxy- and
      deoxyhemoglobin. We also demonstrated that an inaccurate marking of epileptic
      events has a small impact on the detection statistics whereas an inaccurate
      specification of the hemodynamic response function delay decreases drastically
      the detection abilities. Finally, we illustrated the two methods on clinical
      EEG/NIRS data of one patient with focal epilepsy, showing an increase of regional
      Cerebral Blood Volume (rCBV) spatially concordant with the presumed epileptogenic
      focus.

PMID- 21168515
TI  - The dorsal medial frontal cortex is sensitive to time on task, not response
      conflict or error likelihood.
AB  - The dorsal medial frontal cortex (dMFC) is highly active during choice behavior.
      Though many models have been proposed to explain dMFC function, the conflict
      monitoring model is the most influential. It posits that dMFC is primarily
      involved in detecting interference between competing responses thus signaling the
      need for control. It accurately predicts increased neural activity and response
      time (RT) for incompatible (high-interference) vs. compatible (low-interference)
      decisions. However, it has been shown that neural activity can increase with time
      on task, even when no decisions are made. Thus, the greater dMFC activity on
      incompatible trials may stem from longer RTs rather than response conflict. This
      study shows that (1) the conflict monitoring model fails to predict the
      relationship between error likelihood and RT, and (2) the dMFC activity is not
      sensitive to congruency, error likelihood, or response conflict, but is
      monotonically related to time on task.

PMID- 21168516
TI  - Patterns of brain reorganization subsequent to left fusiform damage: fMRI
      evidence from visual processing of words and pseudowords, faces and objects.
AB  - Little is known about the neural reorganization that takes place subsequent to
      lesions that affect orthographic processing (reading and/or spelling). We report
      on an fMRI investigation of an individual with a left mid-fusiform resection that
      affected both reading and spelling (Tsapkini & Rapp, 2010). To investigate
      possible patterns of functional reorganization, we compared the behavioral and
      neural activation patterns of this individual with those of a group of control
      participants for the tasks of silent reading of words and pseudowords and the
      passive viewing of faces and objects, all tasks that typically recruit the
      inferior temporal lobes. This comparison was carried out with methods that
      included a novel application of Mahalanobis distance statistics, and revealed:
      (1) normal behavioral and neural responses for face and object processing, (2)
      evidence of neural reorganization bilaterally in the posterior fusiform that
      supported normal performance in pseudoword reading and which contributed to word
      reading (3) evidence of abnormal recruitment of the bilateral anterior temporal
      lobes indicating compensatory (albeit insufficient) recruitment of mechanisms for
      circumventing the word reading deficit.

PMID- 21168518
TI  - Opposing patterns of neural priming in same-exemplar vs. different-exemplar
      repetition predict subsequent memory.
AB  - The present neuroimaging study examines how repetition-related neural attenuation
      effects differ as a function of the perceptual similarity of the repetition and
      subsequent memory. One previous study (Turk-Browne et al., 2006) reported greater
      attenuation effects for subsequent hits than for misses. Another study (Wagner et
      al., 2000) found that neural attenuation is negatively correlated with subsequent
      memory. These opposing results suggest that repetition-related neural attenuation
      for subsequent hits and misses may be driven by different factors. In order to
      investigate the factors that affect the degree of neural attenuation, we varied
      perceptual similarity between repetitions in a scanned encoding phase that was
      followed by a subsequent memory test outside the scanner. We demonstrated that
      the degree of neural attenuation in the object processing regions depends on the
      interaction between perceptual similarity across repeated presentations and the
      quality their encodings. Specifically, the same areas that decreased neural
      signal for repetitions of same exemplars that were subsequently recognized with
      confidence that the repetitions were identical showed a decrease in neural signal
      for different-exemplar misses but not for the corresponding subsequently
      recognized hits. Our results imply that repetition-related neural attenuation
      should be related to the more efficient processing of perceptual properties of
      the stimuli only if subjects are able to subsequently remember the stimuli.
      Otherwise, the cause of attenuation may be in the failure to encode the stimuli
      on the second presentation as shown by the pattern of neural attenuation for the
      different-exemplar misses.

PMID- 21168517
TI  - White matter integrity in right hemisphere predicts pitch-related grammar
      learning.
AB  - White matter plays an important role in various domains of cognitive function.
      While disruptions in white matter are known to affect many domains of behavior
      and cognition, the ability to acquire grammatical regularities has been mostly
      linked to the left hemisphere, perhaps due to its dependence on linguistic
      stimuli. The role of white matter in the right hemisphere in grammar acquisition
      is yet unknown. Here we show for the first time that in the domain of pitch,
      intact white matter connectivity in right-hemisphere analogs of language areas is
      important for grammar learning. A pitch-based artificial grammar learning task
      was conducted on subjects who also underwent diffusion tensor imaging.
      Probabilistic tractography using seed regions of interest in the right inferior
      frontal gyrus and right middle temporal gyrus showed positive correlations
      between tract volume and learning performance. Furthermore, significant
      correlations were observed between learning performance and FA in white matter
      underlying the supramarginal gyrus, corresponding to the right temporal-parietal
      junction of the arcuate fasciculus. The control task of recognition did not
      correlate with tract volume or FA, and control tracts in the left hemisphere did
      not correlate with behavioral performance. Results show that the right ventral
      arcuate fasciculus is important in pitch-based artificial grammar learning, and
      that brain structures subserving learning may be tied to the hemisphere that
      processes the stimulus more generally.

PMID- 21168520
TI  - Cryptic diversity in a widespread North American songbird: phylogeography of the
      Brown Creeper (Certhia americana).
AB  - The identification of species via morphological characteristics has traditionally
      left cryptic species undescribed in taxa under selection for morphological
      conservation (or a lack of selection for morphological change). Treecreepers
      (Genus: Certhia) have a conserved morphological appearance, making it difficult
      to ascertain relationships in the genus based on morphology alone. Recent genetic
      and song structure studies of Eurasian Treecreepers identified cryptic species
      within Old World Certhia that were previously undescribed using morphological
      characteristics. Here, we use mtDNA to investigate cryptic diversity and patterns
      of diversification in the Brown Creeper (Certhia americana), the single described
      Certhia species in the Americas. Phylogenetic analyses identified six well
      supported geographically-structured clades; the basal divergence separates a
      northern and a southern lineage in the Brown Creeper, likely cryptic species
      previously characterized as many subspecies. Sympatry is prevalent between clades
      in western North America, where possible contact zones warrant further
      investigation. Allopatry appears to be the primary driver of deep phylogeographic
      structure within the Brown Creeper; however, within clade diversity is highly
      correlated with the life history traits of the populations that comprise the
      geographically structured phylogroups.

PMID- 21168519
TI  - Characterization of the corpus callosum in very preterm and full-term infants
      utilizing MRI.
AB  - The corpus callosum is the largest white matter tract, important for
      interhemispheric communication. The aim of this study was to investigate and
      compare corpus callosum size, shape and diffusion characteristics in 106 very
      preterm infants and 22 full-term infants. Structural and diffusion magnetic
      resonance images were obtained at term equivalent. The corpus callosum was
      segmented, cross-sectional areas were calculated, and shape was analyzed.
      Fractional anisotropy, mean, axial and radial diffusivity measures were obtained
      from within the corpus callosum, with additional probabilistic tractography
      analysis. Very preterm infants had significantly reduced callosal cross-sectional
      area compared with term infants (p=0.004), particularly for the mid-body and
      posterior sub-regions. Very preterm callosi were more circular (p=0.01).
      Fractional anisotropy was lower (p=0.007) and mean (p=0.006) and radial (p=0.001)
      diffusivity values were higher in very preterm infants' callosi, particularly at
      the anterior and posterior ends. The volume of tracts originating from the corpus
      callosum was reduced in very preterm infants (p=0.001), particularly for anterior
      mid-body (p=0.01) and isthmus tracts (p=0.04). This study characterizes callosal
      size, shape and diffusion in typically developing infants at term equivalent age,
      and reports macrostructural and microstructural abnormalities as a result of
      prematurity.

PMID- 21168521
TI  - Artesunate mitigates proliferation of tumor cells by alkylating heme-harboring
      nitric oxide synthase.
AB  - Artesunate (ART), a semi-synthetic derivative of antimalarial artemisinin, kills
      cancer cells with uncertain mechanisms. Here, we report for the first time that
      ART may exert the anti-tumor activity by conjugating the prosthetic heme of
      hemoproteins in a hepatoma cell line, HepG2, which was evident by monitoring the
      shift of absorbance from heme (A415) to the ART-heme adduct (A476). Accordingly,
      a transient elevation of A415 was observed with a synchronous burst of nitric
      oxide (NO) and a high rate of survival following incubation of HepG2 with 50 MUM
      ART. In contrast, ART at above 100 MUM led to an abrogation of NO generation and
      a decline of the survival rate in HepG2. These data implied that heme-containing
      nitric oxide synthase (NOS) may represent a major cellular target of ART in
      killing tumor cells.

PMID- 21168522
TI  - The effects of fasting on the metabolic interaction between digestion and
      locomotion in juvenile southern catfish (Silurus meridionalis).
AB  - To investigate the effect of fasting on maintenance metabolism, feeding
      metabolism and aerobic swimming performance as well as their metabolic
      interactions in juvenile southern catfish, we measured the following: (1) the
      postprandial oxygen consumption ((MO2) response (16% body mass meal size) after 0
      (control), 1, 2 and 4 weeks of fasting and (2) the swimming performance of non
      digesting and digesting fish after either 0, 1, 2 or 4 weeks of fasting. The
      fasting groups displayed with lower resting MO2 (MO2(rest)), lower peak
      postprandial MO2 (MO2(peak)), larger energy expenditures and longer digestive
      processes than those of the control groups. The critical swimming speed
      (U(crit)), the active MO2 (MO2(active)) and the metabolic scope (MO2(active) -
      MO2(rest), MS) of both non-digesting and digesting fish all decreased
      progressively after 1, 2 and 4 weeks of fasting, with those of non-digesting fish
      decreased more acutely than digesting fish (P<0.05). Digesting fish displayed
      with a 14%, 23%, 27% and 71% significantly higher MO2(active) than that of non
      digesting fish in the 0-, 1-, 2- and 4-week fasting groups. Digestion only caused
      a significantly lower U(crit) and MS in both the 0- and 1-week fasting groups
      (P<0.05). The MO2 increased greatly with the swimming speed, and digestion caused
      a higher MO2 when compared to that of the fasting fish in any groups. The MO2 of
      fish in the 4-week fasting group was significantly lower than that of other
      groups when the swimming speed was the same. In conclusion, both digestive and
      locomotive functions were down-regulated during fasting. In the 0- and 1-week
      fasting groups, the decreased MS for swimming during digestion caused a lower
      U(crit) (i.e., a digestion priority model). However, because the MO2(active) of
      digesting fish decreased much more slowly than that of fasting fish, the MS of
      the 2- and 4-week fasting groups did not change during digestion, and the fish
      could handle both physiological activities independently (i.e., an additive
      model).

PMID- 21168523
TI  - 5-Aza-2'-deoxycytidine increases sialyl Lewis X on MUC1 by stimulating beta
      galactoside:alpha2,3-sialyltransferase 6 gene.
AB  - Sialyl Lewis X is a tumor-associated antigen frequently found in the advanced
      cancers. However, the mechanism for the production of this cancer antigen is not
      entirely clear. The objective of this study is to examine whether epigenetics is
      involved in the regulation of the formation of this antigen. We observed an
      increase of sialyl Lewis X in HCT15 cells, a colon cancer cell line, treated with
      5-Aza-2'-deoxycytidine. This treatment enhanced the expression of beta
      galactoside:alpha2,3-sialyltransferase 6 gene and sialyl Lewis X on MUC1, and the
      adherence of these cells to E-selectin under dynamic flow conditions. In
      addition, 5-Aza-2'-deoxycytidine treatment inhibited methylation of beta
      galactoside:alpha2,3-sialyltransferase 6 gene and siRNA knockdown of this gene
      drastically reduced sialyl Lewis X without affecting MUC1 expression. We conclude
      that 5-Aza-2'-deoxycytidine treatment increases sialyl Lewis X on MUC1 by
      stimulating the beta-galactoside:alpha2,3-sialyltransferase 6 gene via inhibition
      of DNA methylation. Increased sialyl Lewis X by 5-Aza-2'-deoxycytidine raises a
      concern about the safety of this chemotherapeutic drug. In addition, beta
      galactoside:alpha2,3-sialyltransferase 6 gene may be a potential therapeutic
      target for suppressing tumorigenicity of colon cancer.

PMID- 21168525
TI  - The Global Pertussis Initiative: report from a round table meeting to discuss the
      epidemiology and detection of pertussis, Paris, France, 11-12 January 2010.
AB  - Pertussis remains endemic worldwide and is an important public health problem,
      even in countries with sustained high vaccination coverage. Resurgence of
      pertussis in the post-vaccination era has been reported in many areas of the
      world. The Global Pertussis Initiative (GPI) was established in 2001 to evaluate
      the ongoing problem of pertussis worldwide and to recommend appropriate pertussis
      control strategies. In addition to primary vaccinations, the GPI currently
      recommends a pertussis booster vaccination to pre-school children, adolescents
      and those adults at risk of transmitting Bordetella pertussis infection to
      infants. At a meeting in Paris, France, in January 2010, GPI members discussed
      pertussis surveillance and testing then prepared recommendations on the
      implementation and utilisation of these activities. Issues and projects discussed
      included: national surveillance systems and their suitability for other
      countries; seroprevalence studies; ideal surveillance methodologies; ongoing
      efforts in obtaining biological samples; standardisation of sample treatment;
      culture; real-time polymerase chain reaction (PCR); and likely future advances
      such as antibody detection in saliva. Previous regional meetings of the GPI have
      confirmed that many countries have limited laboratory facilities for the
      detection of pertussis. The GPI hopes that the future introduction of increased
      laboratory capabilities and greater harmonisation of clinical definitions and
      detection methods will lead to enhanced surveillance and a better estimate of the
      burden of pertussis infection worldwide. This article provides a current guide on
      the appropriate use of laboratory diagnostics and optimal surveillance
      methodologies to assist countries in the control of pertussis disease.

PMID- 21168524
TI  - Validation of housekeeping genes as internal controls for studying biomarkers of
      endocrine-disrupting chemicals in disk abalone by real-time PCR.
AB  - Our experiments were designed to identify suitable housekeeping genes (HKGs) in
      disk abalone as internal controls to quantify biomarker expression following
      endocrine disrupting chemicals (EDCs). Relative expression levels of twelve
      candidate HKGs were examined by real-time reverse transcription PCR (qRT-PCR) in
      gill and hepatopancreas of abalone following a 7-day challenge with either
      tributyltin chloride (TBT) or 17beta-estradiol (E2). The expression levels of
      several conventional HKGs, such as 18s rRNA, glyceraldehyde-3-phosphate
      dehydrogenase and beta-actin, were significantly altered by the challenges,
      indicating that they might not be suitable internal controls. Instead, the geNorm
      analysis pinpointed ribosomal protein L-5/ elongation factor 1 and ribosomal
      protein L-5/ succinate dehydrogenase as the most stable HKGs under TBT and E2
      challenges, respectively. Moreover, these three HKGs also showed the highest
      stabilities overall amongst different tissues, genders and EDC challenges. The
      expression of a biomarker gene, cytochrome P450 4B (CYP4), was also investigated
      and exhibited a significant increase after the challenges. Importantly, when
      unsuitable HKGs were used for normalization, the influence of two EDCs on CYP4
      expression was imprecisely overestimated or underestimated, which strongly
      emphasized the importance of selecting appropriately validated HKGs as internal
      controls in biomarker studies.

PMID- 21168526
TI  - A framework for performance and data quality assessment of Radio Frequency
      IDentification (RFID) systems in health care settings.
AB  - OBJECTIVE: RFID offers great opportunities to health care. Nevertheless, prior
      experiences also show that RFID systems have not been designed and tested in
      response to the particular needs of health care settings and might introduce new
      risks. The aim of this study is to present a framework that can be used to assess
      the performance of RFID systems particularly in health care settings. METHODS: We
      developed a framework describing a systematic approach that can be used for
      assessing the feasibility of using an RFID technology in a particular healthcare
      setting; more specific for testing the impact of environmental factors on the
      quality of RFID generated data and vice versa. This framework is based on our own
      experiences with an RFID pilot implementation in an academic hospital in The
      Netherlands and a literature review concerning RFID test methods and current
      insights of RFID implementations in healthcare. The implementation of an RFID
      system within the blood transfusion chain inside a hospital setting was used as a
      show case to explain the different phases of the framework. RESULTS: The
      framework consists of nine phases, including an implementation development plan,
      RFID and medical equipment interference tests, data accuracy- and data
      completeness tests to be run in laboratory, simulated field and real field
      settings. CONCLUSIONS: The potential risks that RFID technologies may bring to
      the healthcare setting should be thoroughly evaluated before they are introduced
      into a vital environment. The RFID performance assessment framework that we
      present can act as a reference model to start an RFID development, engineering,
      implementation and testing plan and more specific, to assess the potential risks
      of interference and to test the quality of the RFID generated data potentially
      influenced by physical objects in specific health care environments.

PMID- 21168527
TI  - Implementing ReliefF filters to extract meaningful features from genetic lifetime
      datasets.
AB  - BACKGROUND: The analysis of survival data allows to evaluate whether in a
      population the genetic exposure is related to the time until an event occurs.
      Owing to the complexity of common human diseases, there is the incipient need to
      develop bioinformatics tools to properly model non-linear high-order interactions
      in lifetime datasets. These tools, such as the survival dimensionality reduction
      algorithm, may suffer from extreme computational costs in large-scale datasets.
      Herein, we address the problem of estimating the quality of attributes, so as to
      extract relevant features from lifetime datasets and to scale down their size.
      METHODS: The ReliefF algorithm was modified and adjusted to compensate for the
      loss of information due to censoring, introducing reclassification and weighting
      schemes. Synthetic lifetime two-locus epistatic datasets of 500 attributes, 400
      800 individuals and different degrees of cumulative heritability and censorship
      were generated. The capability of the survival ReliefF algorithm (sReliefF) and
      of a tuned sReliefF approach to properly select the causative pair of attributes
      was evaluated and compared to univariate selection based on Cox scores.
      RESULTS/CONCLUSIONS: sReliefF methods efficiently scaled down the simulated
      datasets, whilst univariate selection performed no better than random choice.
      These approaches may help to reduce the computational cost and to improve the
      classification task of algorithms that model high-order interactions in presence
      of right-censored data. AVAILABILITY:
      http://sourceforge.net/projects/sdrproject/files/sReliefF/.

PMID- 21168528
TI  - Data mining to improve detection of arrhythmogenic T-wave alternans.

PMID- 21168529
TI  - Cost and yield of adding electrocardiography to history and physical in screening
      Division I intercollegiate athletes: a 5-year experience.
AB  - BACKGROUND: Electrocardiographic screening of intercollegiate athletes is
      controversial because the costs and yield are not well defined. Both the American
      Heart Association (AHA) and the European Society of Cardiology (ESC) have
      different criteria for screening, partly because the populations being screened
      are different. OBJECTIVE: The purpose of this study was to determine the cost and
      yield of a 5-year ECG screening program at a United States Division I college.
      METHODS: At the University of Virginia, all 1,473 competitive athletes over the
      course of 5 years were screened with history and physical and with ECGs using ESC
      guidelines with follow-up testing as dictated by clinical symptoms and ECG
      findings. RESULTS: History and physical alone uncovered five significant cardiac
      abnormalities. ECGs were abnormal in 275 (19%), resulting in 359 additional
      tests. Additional testing confirmed eight significant cardiac abnormalities that
      were not found by history and physical: 1 bicuspid aortic valve, 4 rapidly
      conducting accessory pathways, 1 long QT patient, 1 with frequent premature
      ventricular contractions and low ejection fraction, and 1 with frequent premature
      ventricular contractions but normal ejection fraction. No cases of hypertrophic
      cardiomyopathy were found. Total cost of the program was US $894,870. Cost of
      history and physical screening alone was $343,725 or $68,745 per finding. The
      marginal cost of adding ECG screening, including resulting tests and procedures.
      was US$551,145 or US$68,893 per additional finding. CONCLUSION: ECG screening of
      U.S. college athletes can uncover significant cardiac pathology not discovered by
      history and physical alone. Although ECG screening also results in many false
      positives resulting in additional tests, the overall cost per diagnosis of adding
      ECG screening is similar to that of history and physical screening alone.

PMID- 21168530
TI  - A transcriptome screen in yeast identifies a novel assembly factor for the
      mitochondrial complex III.
AB  - Starting from a transcriptome based study of the spatio-temporal expression of
      yeast genes encoding mitochondrial proteins of unknown function, we have
      identified the gene BCA1 (YLR077W). A FISH analysis showed that the BCA1 mRNA co
      localized with the mitochondrial network. Cellular fractionation revealed that
      Bca1 is bound to the mitochondrial inner-membrane and protrudes into the inter
      membrane space. We show that Bca1 controls an early step in complex III assembly
      and that the supra-molecular organization of Bca1 is dependent upon the assembly
      level of complex III. Thus, Bca1 is a novel assembly factor for the respiratory
      complex III.

PMID- 21168531
TI  - Sequence variations of mitochondrial DNA D-loop region are associated with
      familial nasopharyngeal carcinoma.
AB  - Mitochondrial DNA (mtDNA) D-loop has been identified as a frequent hot spot of
      mutations in various tumors. The aim here was to investigate the sequence
      variations of mitochondrial D-loop region in familial nasopharyngeal carcinoma
      (FNPC) and their possible associations with cancer risk. 29 subjects from 4
      Chinese NPC families and 20 sporadic NPC as well as 122 cases of normal control
      were recruited. mtDNA extracted from peripheral blood was examined by PCR-based
      assay for D-loop sequence variations, followed by sequencing analysis. Compared
      with normal control, four high variations and 6 unrepoted novel polymorphisms
      were found. Particularly, the np16362 and 16519T to C variants show significantly
      higher (100%, 81.8%) and lower (0, 22.7%) frequencies in FNPC and unaffected
      pedigree members, respectively. The occurrence of mitochondrial microsatellite
      instability (mtMSI) at D310 in experimental groups was statistically
      significantly higher than in normal control (53.3%). Likewise, in Base Variation
      Rate consistent with the result, there was a statistically significant difference
      compared with NC (6.05%). Our results indicated that mtDNA exhibited a high rate
      of sequence variants in patients with NPC and pedigree members and the mtDNA
      np16362, np16519 variants and mtMSI at D310 are associated with an increased risk
      of familial nasopharyngeal carcinoma in pedigree members from families with NPC,
      which might be involved in the NPC carcinogenesis.

PMID- 21168532
TI  - Drosophila delta-1-pyrroline-5-carboxylate dehydrogenase (P5CDh) is required for
      proline breakdown and mitochondrial integrity-Establishing a fly model for human
      type II hyperprolinemia.
AB  - Delta-1-pyrroline-5-carboxylate dehydrogenase (P5CDh) is a nuclear-encoded
      mitochondrial enzyme that catalyzes the second step in proline degradation.
      Mutations in human P5CDh cause type II hyperprolinemia, a complex syndrome
      displaying increased serum proline and mental disabilities. Conceptual gene
      CG7145 in Drosophila melanogaster encodes the orthologous DmP5CDh1. The mutant
      allele CG7145(f04633) contains a piggyBac transposon that truncates the enzyme by
      83 residues. Heterozygous (CG7145(f04633)/TM3) individuals developed normally,
      while homozygous (CG7145(f04633)/CG7145(f04633)) individuals displayed proline
      levels twice that of normal, swollen mitochondria, and ultimately larval and
      pupal lethality. We believe this is the first correlation between the loss of
      P5CDh and morphological defects in mitochondria.

PMID- 21168533
TI  - Dynamic regulation of mitochondrial function in preimplantation embryos and
      embryonic stem cells.
AB  - Mitochondrial function is dependent upon regulation of biogenesis and dynamics. A
      number of studies have documented the importance of these organelles in both
      preimplantation embryos and embryonic stem cells (ESCs), however it remains
      unclear how mitochondria respond to their immediate microenvironment through
      modulation of morphology and movement, or whether perturbations in these
      processes will have a significant impact following differentiation/implantation.
      Here we review existing literature on two key aspects of nuclear-mitochondrial
      cross-talk and the dynamic processes involved in mediating mitochondrial function
      through regulation of mitochondrial biogenesis, morphology and movement, with
      particular emphasis on embryos and ESCs.

PMID- 21168534
TI  - Hesperetin protects testicular toxicity of doxorubicin in rat: role of NFkappaB,
      p38 and caspase-3.
AB  - Doxorubicin is a widely used chemotherapeutic agent causing serious dose
      dependent toxicity to non-target tissues such as testis. Its testicular toxicity
      is mainly due to the induction of oxidative stress. Hesperetin exerts its
      beneficial effects against oxidative stress-induced cellular damage. In the
      present investigation, doxorubicin was administered intraperitoneally at the dose
      of 4 mg/kg bw/week for a period of 5 consecutive weeks. Hesperetin was
      administered at the doses of 25, 50 and 100mg/kg bw per oral by gavage for 5
      consecutive days in a week for 5 weeks. Animals were sacrificed 1 week after the
      last injection of doxorubicin. The results of the present study clearly indicate
      the prevention of oxidative stress, DNA damage and the cellular toxicity by
      hesperetin treatment as evident from the analysis of biochemical parameters,
      comet assay, halo assay, Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick
      End Labeling assay, immunohistochemistry and histology. Hesperetin protection
      against doxorubicin-induced germ cell toxicity was further evident from the sperm
      count and sperm head morphological evaluation. Moreover, the role of nuclear
      factor-kappa B, p38 and caspase-3 on hesperetin-mediated protection against
      doxorubicin-induced testicular toxicity was also investigated. The present study
      clearly revealed the amelioration of doxorubicin-induced testicular toxicity by
      the intervention with hesperetin.

PMID- 21168535
TI  - Biodegradable insulin-loaded PLGA microspheres fabricated by three different
      emulsification techniques: investigation for cartilage tissue engineering.
AB  - Growth, differentiation and migration factors facilitate the engineering of
      tissues but need to be administered with defined gradients over a prolonged
      period of time. In this study insulin as a growth factor for cartilage tissue
      engineering and a biodegradable PLGA delivery device were used. The aim was to
      investigate comparatively three different microencapsulation techniques, solid-in
      oil-in-water (s/o/w), water-in-oil-in-water (w/o/w) and oil-in-oil-in-water
      (o/o/w), for the fabrication of insulin-loaded PLGA microspheres with regard to
      protein loading efficiency, release and degradation kinetics, biological activity
      of the released protein and phagocytosis of the microspheres. Insulin-loaded PLGA
      microspheres prepared by all three emulsification techniques had smooth and
      spherical surfaces with a negative zeta potential. The preparation technique did
      not affect particle degradation nor induce phagocytosis by human leukocytes. The
      delivery of structurally intact and biologically active insulin from the
      microspheres was shown using circular dichroism spectroscopy and a MCF7 cell
      based proliferation assay. However, the insulin loading efficiency (w/o/w about
      80%, s/o/w 60%, and o/o/w 25%) and the insulin release kinetics were influenced
      by the microencapsulation technique. The results demonstrate that the w/o/w
      microspheres are most appropriate, providing a high encapsulation efficiency and
      low initial burst release, and thus these were finally used for cartilage tissue
      engineering. Insulin released from w/o/w PLGA microspheres stimulated the
      formation of cartilage considerably in chondrocyte high density pellet cultures,
      as determined by increased secretion of proteoglycans and collagen type II. Our
      results should encourage further studies applying protein-loaded PLGA
      microspheres in combination with cell transplants or cell-free in situ tissue
      engineering implants to regenerate cartilage.

PMID- 21168536
TI  - PINP as an aid for monitoring patients treated with teriparatide.
AB  - Biochemical markers of bone turnover may be useful aids for managing patients
      with osteoporosis. A 12-month, phase 3, multicenter trial of Japanese patients at
      high risk of fracture was conducted to assess the effects of teriparatide 20
      MUg/day on BMD, serum markers of bone turnover, and safety. Two-hundred and seven
      subjects (93% female; median age 70 years) were randomized in double-blind
      fashion 2:1 to teriparatide versus placebo. Bone turnover markers including
      procollagen type I N-terminal propeptide (PINP), bone-specific alkaline
      phosphatase (bone ALP) and type I collagen cross-linked C-telopeptide (CTX) were
      collected at baseline, 1, 3, 6, and 12 months. Lumbar spine, femoral neck, and
      total hip BMD were measured at baseline, 3, 6, and 12 months. Increases in PINP
      at 1 month correlated best with increases in lumbar spine BMD at 12 months
      (r=0.76; P<0.01). The proportions of patients with an increase from baseline in
      PINP >10 MUg/L at 1, 3, and 6 months were 3%, 0%, and 2% in the placebo, and 93%,
      87%, and 83% in the teriparatide group. The proportions of patients with an
      increase in PINP >10 MUg/L at either 1 or 3 months were 3% in the placebo and 95%
      in the teriparatide group (P<0.001). The proportions of patients with a
      significant increase in lumbar spine BMD (increase from baseline >=3%) at 12
      months were 20% in the placebo and 94% in the teriparatide group. The proportions
      of patients with an increase in PINP >10 MUg/L at 1 or 3 months and an increase
      in lumbar spine BMD >=3% at 12 months was 0% of placebo group patients and 92% of
      teriparatide group patients (P<0.001). These data confirm a strong relationship
      between early change in PINP and later change in lumbar spine BMD during
      teriparatide therapy. Also, these results suggest that monitoring with PINP and
      lumbar spine BMD successfully identifies positive responses in most patients
      taking teriparatide and negative responses in most patients not taking
      teriparatide. PINP monitoring may be a useful aid in the management of patients
      with osteoporosis during teriparatide treatment.

PMID- 21168537
TI  - Nicotinic modulation of gene expression in osteoblast cells, MG-63.
AB  - Exposure to nicotine causes a broad range of biological and molecular effects on
      osteoblasts which are known to play a crucial role in bone metabolism and
      fracture healing. Most effects of nicotine on the osteoblasts are long-term
      adaptations at the genomic level. To identify the nicotine-regulated genes, the
      Agilent technologies whole human genome gene expression microarray was performed
      on RNA samples from osteoblast-like cells, MG-63, exposed to 100 MUM nicotine.
      Repeat and cross-controlled microarray analyses revealed 842 genes whose
      expression was consistently altered at P<0.05 level following nicotine treatment.
      Gene ontology analysis suggested effects of nicotine on various biological and
      cellular processes which were associated with survival, proliferation,
      differentiation and apoptosis processes within the cell. Quantitative real-time
      reverse transcriptase PCR analysis confirmed altered expression in 7 out of 9
      genes tested. The identified genes tested in the current study support our
      previous report that nicotine regulates the expression of genes that promote
      osteoblast proliferation and/or anti-apoptosis processes. Furthermore, using
      nicotinic acetylcholine receptor antagonists blocked the majority of the nicotine
      effects, indicating that these changes are dependent on nAChR activation. These
      results established a novel and consistent nicotinic activation of nAChR in
      osteoblast cells which has a broad role affecting cellular physiology through
      modulation of gene expression.

PMID- 21168539
TI  - The osseous endplates in lumbar vertebrae: thickness, bone mineral density and
      their associations with age and disk degeneration.
AB  - INTRODUCTION: As the gateway of nutrient supply, the vertebral endplate is
      essential to maintain the integrity and function of the avascular intervertebral
      disk. While a link between calcium deposition in the endplate and disk
      degeneration is well established from histological studies, findings on the
      association between endplate thickness and age and disk degeneration are
      conflicting. Moreover, the association between endplate bone mineral density
      (BMD) and disk degeneration remains unexplored in humans. OBJECTIVES: To
      determine the thickness and BMD of lumbar spine osseous endplates in men and
      explore their associations with age and disk degeneration. METHODS: From a spine
      archive, 150 cadaveric lumbar vertebrae (L1-L5) from 48 male human spines (mean
      age 50 years, range 21-64) were scanned using micro-CT (MUCT). The osseous
      endplates were extracted from the vertebral body to measure the mean thickness
      and volumetric BMD. The difference between cranial and caudal endplates,
      associations of endplate thickness and BMD with age and discographic degeneration
      pathology were examined. RESULTS: Overall, the mean thickness was 1.03+/-0.24 mm
      for cranial (to disk) endplates and 0.78+/-0.16 mm for caudal endplates. For
      lumbar intervertebral disks, the cranial endplate was significantly thicker and
      denser than the caudal endplate (p<0.001-0.05). Thickness and BMD of endplates
      were independent of age. Based on discography, a trend of more severe disk
      degeneration associated with greater thickness in both the cranial and caudal
      endplates was observed, and was most marked in severely degenerated disks
      (p<0.05). However, no evidence was detected for a link between more severe disk
      degeneration and elevated endplate BMD (p>0.05). CONCLUSIONS: In the lumbar
      spine, both the thickness and BMD of endplates were independent of age, which
      ranged from 21 to 64 years. The endplates cranial to intervertebral disks were
      thicker and had higher BMD than the corresponding caudal endplates. Judged from
      discography, more degeneration in the adjacent intervertebral disk was associated
      with greater endplate thickness, but not higher endplate BMD. Thus, endplate
      sclerosis, reflecting elevated endplate BMD, may not be a risk factor for disk
      pathology in men.

PMID- 21168538
TI  - Effects of age and sex on the strength and cortical thickness of the femoral
      neck.
AB  - A group of 48 men (22 aged 65-75 years, 26 aged 80-90 years) and 59 women (32
      aged 65-75 years, 27 aged 80-90 years) were enrolled in the Age, Gene/Environment
      Susceptibility-Reykjavik study and imaged with in vivo volumetric Quantitative
      Computed Tomography (QCT) to investigate the effects of age and sex on femoral
      neck structure and strength. Femoral neck cross-sectional moment of inertia for
      bending directions near those of standing and walking (I(AP)), bending strength
      (M(y)), and axial compressive strength (F(y)) were computed at the location of
      minimum cross-sectional area (minCSA). Local cortical thickness was computed in
      the inferior femoral neck based on density profiles extending through the cortex
      of the minCSA femoral neck section. Multivariate models accounting for height,
      weight, and age group (younger or older) showed that men had a 46% higher M(y)
      and a 23% higher F(y) than women, while women had a 13% thicker inferior cortex
      than men. Cortical thickness in the inferoposterior region of the femoral neck
      was significantly related to bending and axial strength after adjusting for
      overall volumetric bone mineral density. Both minCSA and I(AP) were higher in the
      older, gender-pooled age group, but F(y) and M(y) did not differ between the two
      age groups. The results suggest that age-related expansion of the femoral neck
      primarily occurs in the superior and inferior directions and helps maintain
      homeostasis of femoral neck stiffness and strength. The higher bending strength
      of the male femoral neck may partly explain why elderly men have a lower risk of
      hip fracture than elderly women.

PMID- 21168540
TI  - Effects of astilbic acid on airway hyperresponsiveness and inflammation in a
      mouse model of allergic asthma.
AB  - Bronchial asthma is characterized by chronic lung inflammation, airway
      hyperresponsiveness (AHR), and airway remodeling. Astilbic acid, extracted from
      the medicinal herb Astilbe chinensis, is used as a headache remedy in traditional
      medicine and has anti-pyretic and analgesic effects. However, the effect of
      astilbic acid on asthma remains to be established. In the present study, we
      therefore examined the effect of astilbic acid in a mouse model in which asthma
      was established by sensitization and challenge with ovalbumin (OVA). Astilbic
      acid inhibited OVA-induced AHR to inhaled methacholine and significantly
      suppressed the levels of T-helper 2-type cytokines (including IL [interleukin]-4,
      IL-5, and IL-13) and inflammatory cells (including eosinophils) in
      bronchoalveolar lavage (BAL) fluid. Histochemical analysis revealed reduced
      goblet cell hyperplasia and mucus production, as well as attenuated eosinophil
      rich leukocyte infiltration, in the astilbic acid-treated group, compared with
      OVA-challenged mice. Moreover, the compound significantly inhibited synthesis of
      IL-4-, IL-5-, IL-13-, IL-17-, and eotaxin-encoding mRNA following asthma
      induction in lung tissue, in addition to suppressing the immunoglobulin E (IgE)
      response to asthma in both BAL fluid and serum. Our results indicate that
      astilbic acid has great potential as a therapeutic candidate for the treatment of
      asthma.

PMID- 21168541
TI  - Lectin purified from Musca domestica pupa up-regulates NO and iNOS production via
      TLR4/NF-kappaB signaling pathway in macrophages.
AB  - The present study reported that nitric oxide (NO) was up-regulated by the
      induction of lectin purified from Musca domestica pupa (MPL) in macrophages
      without cytotoxicity. The mRNA expression and protein secretion of inducible
      nitric oxide synthase (iNOS) were strongly induced by MPL treatments. Subsequent
      investigation revealed that the nuclear factor-kappaB (NF-kappaB) inhibitory
      kappaB (IkappaB) in endochylema was inhibited and NF-kappaB translocated into the
      nucleus after MPL treatment. Meanwhile, the IKKbeta was strongly induced and the
      production of the toll-like receptor 4 (TLR4) was significantly up-regulated.
      Moreover, MPL increased NO production via inducing the expression of iNOS through
      the activation of NF-kappaB, which suggested that MPL probably acted as an
      activating agent of the NF-kappaB activation.

PMID- 21168542
TI  - NK cell-based approach for screening novel functional immune genes.
AB  - The human genome project provides extensive opportunities for the discovery of
      novel functional immune genes. In order to find innate immune genes that might
      regulate the function of NK cells from a cDNA library, we used an NK cell line,
      NK-92, as a platform to screen candidate genes. After comparing with other gene
      transfer methods, electroporation was selected as the best gene transfection
      approach to deliver cDNA expression plasmids containing candidate genes into the
      NK-92 cells. When the transferred gene was stably expressed in NK-92 cells, the
      functional changes in the NK-92 cells were examined, including cytotoxicity,
      cytolytic molecules, cytokine production, and proliferation. Two novel genes were
      selected as functional genes that regulate NK cell function from among more than
      100 candidate genes, for which the proliferation and cytotoxicity of NK-92 cells
      were examined as primary indicators. This was followed by extensive flow
      cytometry analysis and RT-PCR. The primary data indicated that the two novel
      genes negatively influenced the cytotoxicity of NK-92 cells by inhibiting the
      expression of several activating receptors and immune functional genes.
      Therefore, we describe an efficient method for the discovery of novel functional
      genes in NK cells by using an NK cell line as a screening platform.

PMID- 21168543
TI  - Modulatory effect of anisodamine on airway hyper-reactivity and eosinophilic
      inflammation in a murine model of allergic asthma.
AB  - Anisodamine, a peripheral muscarinic receptor antagonist, is a naturally
      occurring atropine derivative that has been isolated, synthesized and
      characterized by scientists in China. In the present investigation, we evaluated
      the modulatory effects of anisodamine on airway hyper-reactivity and inflammation
      in a murine model of allergic asthma. Asthma model was induced successfully by
      ovalbumin. The activation of cells, airway eosinopilia, cytokine production, and
      airway function were examined. Our results collectively show that anisomanine
      could significantly suppress the accumulation of eosinophils into the airways and
      dramatically inhibited the histological changes in OVA-induced mice.
      Additionally, anisodamine could restore the Th1/Th2 balance in BALF by
      downregulating the level of Th2 cell-associated cytokine IL-4 (p<0.01) and
      upregulating the level of Th1 cell-associated cytokine IFN-gamma (p<0.01). In
      addition, pretreatment with anisodamine also showed strong suppression of
      allergen-induced bronchial hyper-reactivity with maximum contraction decreasing
      from 0.45 +/- 0.02 g to 0.28 +/- 0.03 g (p<0.01). These results suggested the
      modulatory effects of anisodamine on Th1/Th2 balance by enhancing Th1-related and
      suppressing Th2-related parameters, as well as its potential application in
      airway hyper-reactivity and eosinophilic inflammation.

PMID- 21168544
TI  - Ion mobility spectrometry: a valuable tool for kinetic studies in enzymology.
AB  - The inherent characteristics of IMS such as reduced measurement time, in the
      seconds time scale, sensitivity and selectivity make this technique an ideal
      methodology for enzyme reaction monitoring. The capability of IMS in the
      determination of enzyme kinetics and inhibition studies by the analysis of
      substrate depletion and/or product formation using only a few microliters of
      solution has been successfully demonstrated on the example of acetylcholine
      hydrolysis catalyzed by acetylcholinesterase (AChE) and inhibited by neostigmine
      and galanthamine. Michaelis-Menten and Lineweaver-Burk plots were obtained for
      the enzyme catalyzed reaction with and without neostigmine and galanthamine
      inhibition at two different inhibitor concentrations. Typical plots of
      competitive inhibitors were obtained agreeing well with previous results
      published in the literature. IMS procedure provided a limit of detection for
      acetylcholine in the low ppm range, a precision of 4.8% and an analysis frequency
      of 40s, being those analytical characteristics appropriate to perform enzyme
      kinetic studies. IMS offers a new and efficient tool to study enzyme reactions
      either as a high throughput screening tool for hit discovery and lead development
      for drug discovery proposes or to indirectly perform enzymological studies.

PMID- 21168545
TI  - A novel approach for the determination of paracetamol based on the reduction of N
      acetyl-p-benzoquinoneimine formed on the electrochemically treated pencil
      graphite electrode.
AB  - A novel approach was proposed for the simple and rapid electrochemical
      determination of paracetamol (PC) in the presence of uric acid in body fluids.
      The voltammetric determination of PC is based on the electrochemical reduction of
      N-acetyl-p-benzoquinoneimine formed simultaneously on the electrochemically
      treated pencil graphite (ETPG) electrode during the measurement. ETPG electrodes
      were prepared by the potential cycling between -0.3V and +2.0V in 0.1M H(3)PO(4)
      solution. The electrochemical performance of the ETPG electrode was evaluated by
      adsorptive transfer stripping differential pulse voltammetry (ATSDPV). The
      resulting sensor showed good performance for the determination of PC in human
      blood serum samples with a linear range of 0.05-2.5 MUM and a highly reproducible
      response (RSD of 3.1%). The calculated detection limit was 2.5 nM (S/N=3). The
      proposed method does not require any sample pretreatment, prevents the
      interference of uric acid and allows the determination of PC directly in blood
      serum samples.

PMID- 21168546
TI  - CYP450 biosensors based on screen-printed carbon electrodes for the determination
      of cocaine.
AB  - A new electrochemical method has been described and characterized for the
      determination of cocaine using screen-printed biosensors. The enzyme cytochrome
      P450 was covalently attached to screen-printed carbon electrodes. Experimental
      design methodology has been performed to optimize the pH and the applied
      potential, both variables that have an influence on the chronoamperometric
      determination of the drug. This method showed a reproducibility of 3.56% (n=4)
      related to the slopes of the calibration curves performed in the range from 19 up
      to 166nM. It has been probed the used of this kind of biosensors in the
      determination of cocaine in street samples, with an average capability of
      detection of 23.05+/-3.53nM (n=3, alpha=beta=0.05).

PMID- 21168547
TI  - Stripping voltammetric detection of mercury(II) based on a surface ion imprinting
      strategy in electropolymerized microporous poly(2-mercaptobenzothiazole) films
      modified glassy carbon electrode.
AB  - This work reports a surface ion imprinting strategy in electropolymerized
      microporous poly(2-mercaptobenzothiazole) (MPMBT) films at the surface of glassy
      carbon electrode (GCE) for the electrochemical detection of Hg(II). The Hg(II)
      imprinted MPMBT/GCE exhibits larger binding to functionalized capacity, faster
      binding kinetics and higher selectivity to template Hg(II) due to their high
      ratio of surface-imprinted sites, larger surface-to-volume ratios, the complete
      removal of Hg(II) templates and larger affinity to Hg(II). The square wave anodic
      stripping voltammetry (SW ASV) response of the Hg(II)-imprinted MPMBT/GCE to
      Hg(II) is ca. 3.0 and 5.9 times larger than that at the direct imprinted poly(2
      mercaptobenzothiazole) modified GCE and non-imprinted MPMBT/GCE sensor,
      respectively; and the detection limit for Hg(II) is 0.1nM (which is well below
      the guideline value given by the World Health Organization). Excellent wide
      linear range (1.0-160.0nM) and good repeatability (relative standard deviation of
      2.5%) were obtained for Hg(II). The interference experiments showed that mercury
      signal was not interfered in the presence of Pb(II), Cd(II), Zn(II), Cu(II) and
      Ag(I), respectively. These values, particularly the high sensitivity and
      excellent selectivity compared favorably with previously reported methods in the
      area of electrochemical Hg(II) detection, demonstrate the feasibility of using
      the prepared Hg(II)-imprinted MPMBT/GCE for efficient determination of Hg(II) in
      aqueous environmental samples.

PMID- 21168548
TI  - Selective pressurized liquid extraction of estrogenic compounds in soil and
      analysis by gas chromatography-mass spectrometry.
AB  - A selective pressurized liquid extraction (SPLE) method, followed by gas
      chromatography-mass spectrometry (GC-MS), for the simultaneous extraction and
      clean-up of estrone (E1), 17beta-estradiol (E2), 17alpha-ethynylestradiol (EE2),
      estriol (E3) and bisphenol A (BPA) from soil samples is described. The on-line
      clean-up of soil by SPLE was achieved using different organic matter retainers,
      including silica, alumina and Florisil, the most effective being silica. Thus,
      different amounts of silica, in conjunction with different extraction solvents
      (acetone, ethyl acetate, isohexane and dichloromethane), either alone or in
      combination, were used to extract the target chemicals from spiked soil samples.
      It was shown that 3g silica resulted in satisfactory rates of recovery of target
      compounds and acetone:dichloromethane (1:3, v/v) was efficient in extracting and
      eluting estrogenic compounds for SPLE. Variables affecting the SPLE efficiency,
      including temperature and pressure were studied; the optimum parameters were 60
      degrees C and 1500 psi, respectively. The limits of detection (LODs) of the
      proposed method were 0.02-0.37 ng g(-1) for the different estrogenic chemicals
      studied. The outputs using the proposed method were linear over the range from
      0.1 to 120 ng g(-1) for E1, E2, EE2, 0.2-120 ng g(-1) for E3, and 0.5-120 ng g(
      1) for BPA. The optimized method was further verified by performing spiking
      experiments in natural soil matrices; good rates of recovery and reproducibility
      were achieved for all selected compounds and the method was successfully applied
      to soil samples from Northeast Scotland, for the determination of the target
      compounds.

PMID- 21168549
TI  - Strategy of using microsome-based metabolite production to facilitate the
      identification of endogenous metabolites by liquid chromatography mass
      spectrometry.
AB  - One of the challenges in metabolomic profiling of complex biological samples is
      to identify new and unknown compounds. Typically, standards are used to help
      identify metabolites, yet standards cannot be purchased or readily synthesized
      for many unknowns. In this work we present a strategy of using human liver
      microsomes (HLM) to metabolize known endogenous human metabolites (substrates),
      producing potentially new metabolites that have yet to be documented. The
      metabolites produced by HLM can be tentatively identified based on the associated
      substrate structure, known metabolic processes, tandem mass spectrometry (MS/MS)
      fragmentation patterns and, if necessary, accurate mass measurements. Once
      identified, these metabolites can be used as references for identification of the
      same compounds in complex biological samples. As a proof of principle, a total of
      9 metabolites have been identified from individual HLM incubations using 5
      different substrates. Each metabolite was used as a standard. In the analysis of
      human urine sample by liquid chromatography MS/MS, four spectral matches were
      found from the 9 microsome-produced metabolite standards. Two of them have
      previously been documented as endogenous human metabolites, the third is an
      isomer of a microsome-metabolite and the fourth compound has not been previously
      reported and is also an isomer of a microsome-metabolite. This work illustrates
      the feasibility of using microsome-based metabolism to produce metabolites of
      endogenous human metabolites that can be used to facilitate the identification of
      unknowns in biological samples. Future work on improving the performance of this
      strategy is also discussed.

PMID- 21168550
TI  - The use of high performance liquid chromatography-quadrupole time-of-flight mass
      spectrometry coupled to advanced data mining and chemometric tools for
      discrimination and classification of red wines according to their variety.
AB  - In this study, the potential of high performance liquid chromatography coupled to
      quadrupole time-of-flight mass spectrometry (HPLC-QTOFMS) for metabolomic
      profiling of red wine samples was examined. Fifty one wines representing three
      varieties (Cabernet Sauvignon, Merlot, and Pinot Noir) of various geographical
      origins were sourced from the European and US retail market. To find compounds
      detected in analyzed samples, an automated compound (feature) extraction
      algorithm was employed for processing background subtracted single MS data.
      Stepwise reduction of the data dimensionality was followed by principal component
      analysis (PCA) and partial least square-discriminant analysis (PLS-DA) which were
      employed to explore the structure of the data and construct classification
      models. The validated PLS-DA model based on data recorded in positive ionization
      mode enabled correct classification of 96% of samples. Determination of molecular
      formula and tentative identification of marker compound was carried out using
      accurate mass measurement of full single MS spectra. Additional information was
      obtained by correlating the fragments obtained by MS/MS accurate mass spectra
      using the QTOF with collision induced dissociation (CID) of precursor ions.

PMID- 21168551
TI  - Ultra-sensitive DNA assay based on single-molecule detection coupled with
      fluorescent quantum dot-labeling and its application to determination of
      messenger RNA.
AB  - An ultra-sensitive single-molecule detection (SMD) method for quantification of
      DNA using total internal reflection fluorescence microscopy (TIRFM) coupled with
      fluorescent quantum dot (QD)-labeling was developed. In this method, the target
      DNA (tDNA) was captured by the capture DNA immobilized on the silanized coverslip
      blocked with ethanolamine and bovine serum albumin. Then, the QD-labeled probe
      DNA was hybridized to the tDNA. Ten fluorescent images of the QD-labeled sandwich
      DNA hybrids on the coverslip were taken by a high-sensitive CCD. The tDNA was
      quantified by counting the bright spots on the images using a calibration curve.
      The LOD of the method was 1*10(-14)molL(-1). Several key factors, including image
      acquirement, fluorescence probe, substrate preparation, noise elimination from
      solutions and glass coverslips, and nonspecific adsorption and binding of
      solution-phase detection probes were discussed in detail. The method could be
      applied to quantify messenger RNA (mRNA) in cells. In order to determine mRNA,
      double-stranded RNA-DNA hybrids consisting of mRNA and corresponding cDNA were
      synthesized from the cellular mRNA template using reverse transcription in the
      presence of reverse transcriptase. After removing the mRNA in the double-stranded
      hybrids using ribonuclease, cDNA was quantified using the SMD-based TIRFM.
      Osteopontin mRNA in decidual stromal cells was chosen as the model analyte.

PMID- 21168552
TI  - Optical ammonia gas sensor based on a porous silicon rugate filter coated with
      polymer-supported dye.
AB  - An ammonia gas sensor chip was prepared by coating an electrochemically-etched
      porous Si rugate filter with a chitosan film that is crosslinked by
      glycidoxypropyltrimethoxysilane (GPTMS). The bromothylmol blue (BTB), a pH
      indicator, was loaded in the film as ammonia-sensing molecules. White light
      reflected from the porous Si has a narrow bandwidth spectrum with a peak at 610
      nm. Monitoring reflective optical intensity at the peak position allows for
      direct, real-time observation of changes in the concentration of ammonia gas in
      air samples. The reflective optical intensity decreased linearly with increasing
      concentrations of ammonia gas over the range of 0-100 ppm. The lowest detection
      limit was 0.5 ppm for ammonia gas. At optimum conditions, the full response time
      of the ammonia gas sensor was less than 15s. The sensor chip also exhibited a
      good long-term stability over 1 year. Therefore, the simple sensor design has
      potential application in miniaturized optical measurement for online ammonia gas
      detection.

PMID- 21168553
TI  - Development of direct competitive enzyme-linked aptamer assay for determination
      of dopamine in serum.
AB  - A rapid and cost-effective screening method based on a competitive enzyme-linked
      aptamer assay (ELAA) for dopamine (DA) in serum has been optimized and validated.
      In this paper, we report advantageous sensitivity and specificity of aptamer
      assays as compared to the existing antibody based-immunoassays. The RNA aptamer
      (67 mer) was immobilized via site-directed immobilization with biotin both at the
      3'-end on aptamer and at neutravidin plate. Various factors such as incubation
      temperature, divalent ion - Mg(2+) ion and treatment of serum solution were
      evaluated for the performance of ELAA. The aptamer was incubated for 1h at 4
      degrees C in the assay buffer containing 5 mM Mg(2+) ion, and serum was diluted
      (1:9, serum:assay buffer) and filtrated through a 3 kDa dialysis membrane to
      extract the proteins present in the serum. Assay was performed with 0.01 MUg mL(
      1) of aptamer and 1.205*10(-7)M DA-HRP conjugate using the optimized method. A
      dose-response curve was constructed, and the limit of detection and a dynamic
      range for the DA were determined as 1.0*10(-12)M and four orders (1.0*10(-7)M to
      5.0*10(-11) M) of magnitude, respectively. The correlation diagram of the
      absorbance obtained both in buffer and in serum has shown a good agreement with
      the correlation coefficient (R(2)=0.9872): Abs. (in serum)=0.9612*Abs. (in
      buffer)-0.0556. The cross-reactivity evaluation demonstrated that norepinephrine
      showed some cross-reactivity (3.68%) whereas 3-methoxytyramine, epinephrine,
      homovanillic acid and 3,4-dihydroxyphenylacetic acid showed almost no cross
      reactivity (<1%). Percent recoveries of DA in serum were quite satisfactory
      (~95%). This paper describes usefulness of the aptamer assay in monitoring DA in
      human serum.

PMID- 21168554
TI  - Sensitive and specific detection of potentially allergenic almond (Prunus dulcis)
      in complex food matrices by Taqman((r)) real-time polymerase chain reaction in
      comparison to commercially available protein-based enzyme-linked immunosorbent
      assay.
AB  - Currently, causative immunotherapies are lacking in food allergy. The only option
      to prevent allergic reactions in susceptible individuals is to strictly avoid the
      offending food. Thus, reliable labelling of allergenic constituents is of major
      importance, but can only be achieved if appropriate specific and sensitive
      detection techniques for foods with allergenic potential are available. Almond is
      an allergenic food that requires mandatory labelling on prepackaged foods and
      belongs to the genus Prunus. Species of this genus are phylogenetically closely
      related. We observed commercially available almond specific ELISA being highly
      cross-reactive with other foods of the Prunoideae family, resulting in a false
      positive detection of up to 500,000 mg kg(-1) almond. Previously published PCR
      methods were reported to be cross-reactive with false positive results >1200 mg
      kg(-1). We describe the development of a novel almond specific real-time PCR,
      based on mutated mismatch primers and sequence specific Taqman((r)) probe
      detection, in comparison with two quantitative commercially available ELISA. PCR
      sensitivity was investigated with chocolate, chocolate coating and cookies spiked
      between 5 and 100,000 mg kg(-1) almond. In all matrices almond was reproducibly
      detected by real-time PCR at the lowest spike level of 5 mg kg(-1). Further,
      between 100 and 100,000 mg kg(-1) spiked almond, the method featured good
      correlation between quantified copy numbers and the amount of spiked almond.
      Within this range a similar relation between detectable signal and amount of
      almond was observed for both PCR and ELISA. In contrast to ELISA the Taqman((r))
      real-time PCR method was highly specific in 59 food items with negligible cross
      reactivity for a very limited number of Prunoideae foods. The real-time PCR
      analysis of 24 retail samples was in concordance with ELISA results: 21% (n=5)
      contained undeclared almond. This is the first completely disclosed real-time PCR
      method for a specific and potentially quantitative almond detection. This PCR
      method detects almond at a level where severe allergic reactions should not be
      expected for the majority of the almond allergic individuals.

PMID- 21168555
TI  - Determination of the spectrum of low molecular mass organic acids in urine by
      capillary electrophoresis with contactless conductivity and ultraviolet
      photometric detection--an efficient tool for monitoring of inborn metabolic
      disorders.
AB  - A mixture of 29 organic acids (OAs) occurring in urine was analyzed by capillary
      electrophoresis (CE) with capacitively coupled contactless conductivity detection
      (C(4)D) and UV photometric detection. The optimized analytical system involved a
      100 cm long polyacrylamide-coated capillary (50 MUm i.d.) and the background
      electrolyte of 20mM 2-morpholinoethanesulfonic acid (MES)/NaOH+10% (v/v)
      methanol, pH 6.0 (pH is related to the 20mM MES/NaOH buffer in water). The LOD
      values obtained by C(4)D for the OAs which do not absorb UV radiation range from
      0.6 MUM (oxalic acid) to 6.8 MUM (pyruvic acid); those obtained by UV photometry
      for the remaining OAs range from 2.9 MUM (5-hydroxy-3-indoleacetic acid) to 10.2
      MUM (uric acid). The repeatability of the procedure developed is characterized by
      the coefficients of variation, which vary between 0.3% (tartaric acid) and 0.6%
      (5-hydroxy-3-indoleacetic acid) for the migration time and between 1.3% (tartaric
      acid) and 3.5% (lactic acid) for the peak area. The procedure permitted
      quantitation of 20 OAs in a real urine sample and was applied to monitoring of
      the occurrence of the inborn metabolic fault of methylmalonic aciduria.

PMID- 21168556
TI  - Automatic twin vessel recrystallizer. Effective purification of acetaminophen by
      successive automatic recrystallization and absolute determination of purity by
      DSC.
AB  - I describe an interchangeable twin vessel (J, N) automatic glass recrystallizer
      that eliminates the time-consuming recovery and recycling of crystals for
      repeated recrystallization. The sample goes in the dissolution vessel J
      containing a magnetic stir-bar K; J is clamped to the upper joint H of
      recrystallizer body D. Empty crystallization vessel N is clamped to the lower
      joint M. Pure solvent is delivered to the dissolution vessel and the
      crystallization vessel via the head of the condenser A. Crystallization vessel is
      heated (P). The dissolution reservoir is stirred and heated by the solvent vapor
      (F). Continuous outflow of filtrate E out of J keeps N at a stable boiling
      temperature. This results in efficient dissolution, evaporation and separation of
      pure crystals Q. Pure solvent in the dissolution reservoir is recovered by
      suction. Empty dissolution and crystallization vessels are detached. Stirrer
      magnet is transferred to the crystallization vessel and the role of the vessels
      are then reversed. Evacuating mother liquor out of the upper twin vessel, the
      apparatus unit is ready for the next automatic recrystallization by refilling
      twin vessels with pure solvent. We show successive automatic recrystallization of
      acetaminophen from diethyl ether obtaining acetaminophen of higher melting
      temperatures than USP and JP reference standards by 8* automatic
      recrystallization, 96% yield at each stage. Also, I demonstrate a novel approach
      to the determination of absolute purity by combining the successive automatic
      recrystallization with differential scanning calorimetry (DSC) measurement
      requiring no reference standards. This involves the measurement of the criterial
      melting temperature T(0) corresponding to the 100% pure material and quantitative
      DeltaT in DSC based on the van't Hoff law of melting point depression. The purity
      of six commercial acetaminophen samples and reference standards and an eight
      times recrystallized product evaluated were 98.8 mol%, 97.9 mol%, 99.1 mol%, 98.3
      mol%, 98.4 mol%, 98.5 mol% and 99.3 mol% respectively.

PMID- 21168557
TI  - Investigation of polar stationary phases for the separation of sympathomimetic
      drugs with nano-liquid chromatography in hydrophilic interaction liquid
      chromatography mode.
AB  - In this study, the retention and selectivity of a mixture of basic polar drugs
      were investigated in hydrophilic interaction chromatographic conditions (HILIC)
      using nano-liquid chromatography (nano-LC). Six sympathomimetic drugs including
      ephedrine, norephedrine, synephrine, epinephrine, norepinephrine and
      norphenylephrine were separated by changing experimental parameters such as
      stationary phase, acetonitrile (ACN) content, buffer pH and concentration, column
      temperature. Four polar stationary phases (i.e. cyano-, diol-, aminopropyl-silica
      and Luna HILIC, a cross-linked diol phase) were selected and packed into fused
      silica capillary columns of 100 MUm internal diameter (i.d.). Among the four
      stationary phases investigated a complete separation of the all studied compounds
      was achieved with aminopropyl silica and Luna HILIC stationary phases only. Best
      chromatographic results were obtained employing a mobile phase composed by
      ACN/water (92/8, v/v) containing 10mM ammonium formate buffer pH 3. The influence
      of the capillary temperature on the resolution of the polar basic drugs was
      investigated in the range between 10 and 50 degrees C. Linear correlation of lnk
      vs. 1/T was observed for all the columns; DeltaH degrees  values were negative
      with Luna HILIC and positive with aminopropyl- and diol-silica stationary phases,
      demonstrating that different mechanisms were involved in the separation. To
      compare the chromatographic performance of the different columns, Van Deemter
      curves were also investigated.

PMID- 21168558
TI  - Rapid isolation of plutonium in environmental solid samples using sequential
      injection anion exchange chromatography followed by detection with inductively
      coupled plasma mass spectrometry.
AB  - This paper reports an automated analytical method for rapid determination of
      plutonium isotopes ((239)Pu and (240)Pu) in environmental solid extracts. Anion
      exchange chromatographic columns were incorporated in a sequential injection (SI)
      system to undertake the automated separation of plutonium from matrix and
      interfering elements. The analytical results most distinctly demonstrated that
      the crosslinkage of the anion exchanger is a key parameter controlling the
      separation efficiency. AG 1-*4 type resin was selected as the most suitable
      sorbent material for analyte separation. Investigation of column size effect upon
      the separation efficiency revealed that small-sized (2 mL) columns sufficed to
      handle up to 50 g of environmental soil samples. Under the optimum conditions,
      chemical yields of plutonium exceeded 90% and the decontamination factors for
      uranium, thorium and lead ranged from 10(3) to 10(4). The determination of
      plutonium isotopes in three standard/certified reference materials (IAEA-375
      soil, IAEA-135 sediment and NIST-4359 seaweed) and two reference samples (Irish
      Sea sediment and Danish soil) revealed a good agreement with reference/certified
      values. The SI column-separation method is straightforward and less labor
      intensive as compared with batch-wise anion exchange chromatographic procedures.
      Besides, the automated method features low consumption of ion-exchanger and
      reagents for column washing and elution, with the consequent decrease in the
      generation of acidic waste, thus bearing green chemical credentials.

PMID- 21168559
TI  - Review: Authentication and traceability of foods from animal origin by polymerase
      chain reaction-based capillary electrophoresis.
AB  - This work presents an overview of the applicability of PCR-based capillary
      electrophoresis (CE) in food authentication and traceability of foods from animal
      origin. Analytical approaches for authenticating and tracing meat and meat
      products and fish and seafood products are discussed. Particular emphasis will be
      given to the usefulness of genotyping in food tracing by using CE-based genetic
      analyzers.

PMID- 21168560
TI  - Design of experiments on 135 cloned poplar trees to map environmental influence
      in greenhouse.
AB  - To find and ascertain phenotypic differences, minimal variation between
      biological replicates is always desired. Variation between the replicates can
      originate from genetic transformation but also from environmental effects in the
      greenhouse. Design of experiments (DoE) has been used in field trials for many
      years and proven its value but is underused within functional genomics including
      greenhouse experiments. We propose a strategy to estimate the effect of
      environmental factors with the ultimate goal of minimizing variation between
      biological replicates, based on DoE. DoE can be analyzed in many ways. We present
      a graphical solution together with solutions based on classical statistics as
      well as the newly developed OPLS methodology. In this study, we used DoE to
      evaluate the influence of plant specific factors (plant size, shoot type, plant
      quality, and amount of fertilizer) and rotation of plant positions on height and
      section area of 135 cloned wild type poplar trees grown in the greenhouse.
      Statistical analysis revealed that plant position was the main contributor to
      variability among biological replicates and applying a plant rotation scheme
      could reduce this variation.

PMID- 21168561
TI  - Application of in-vial membrane assisted solvent extraction to the determination
      of polycyclic aromatic hydrocarbons in seawater by gas chromatography-mass
      spectrometry.
AB  - A device for membrane assisted solvent extraction from an aqueous sample to an
      organic solvent within a micro-vial compatible with a chromatography auto-sampler
      was used to extract trace amounts of seven polycyclic aromatic hydrocarbons from
      seawater. The device consisted in an assembly of a volumetric flask containing
      the sample and a micro-vial containing the organic solvent by means of a screw
      stopper in which the septum was replaced by a sized piece of a membrane.
      Extraction conditions (nature of the organic solvent, extraction time, presence
      of ethanol in the donor phase, ionic content of the donor phase, characteristics
      of the membrane and volumes of donor and acceptor phases) were studied in order
      to find the conditions for maximum extraction. Analytical performance
      characteristics have also been established. The extraction efficiency was between
      12.5 and 23%, which implies an enrichment factor value above 40. The
      repeatability and reproducibility were in the range of 8.6-10.0% and 13-19%,
      respectively. Detection limits were in the range of 24-39 ng L(-1). Nine seawater
      samples have been studied. Most of the concentrations were under the limits of
      detection. Naphthalene and phenanthrene contents have been determined in a sample
      using the method of standard additions, and concentrations 100 and 91 ng L(-1),
      respectively.

PMID- 21168562
TI  - Separation, concentration and determination of chloramphenicol in environment and
      food using an ionic liquid/salt aqueous two-phase flotation system coupled with
      high-performance liquid chromatography.
AB  - Ionic liquid-salt aqueous two-phase flotation (ILATPF) is a novel, green, non
      toxic and sensitive samples pretreatment technique. ILATPF coupled with high
      performance liquid chromatography (HPLC) was developed for the analysis of
      chloramphenicol, which combines ionic liquid aqueous two-phase system (ILATPS)
      based on imidazolium ionic liquid (1-butyl-3-methylimidazolium chloride,
      [C(4)mim]Cl) and inorganic salt (K(2)HPO(4)) with solvent sublation. In ILATPF
      systems, phase behaviors of the ILATPF were studied for different types of ionic
      liquids and salts. The sublation efficiency of chloramphenicol in [C(4)mim]Cl
      K(2)HPO(4) ILATPF was influenced by the types of salts, concentration of
      K(2)HPO(4) in aqueous solution, solution pH, nitrogen flow rate, sublation time
      and the amount of [C(4)mim]Cl. Under the optimum conditions, the average
      sublation efficiency is up to 98.5%. The mechanism of ILATPF contains two
      principal processes. One is the mechanism of IL-salt ILATPS formation, the other
      is solvent sublation. This method was practical when applied to the analysis of
      chloramphenicol in lake water, feed water, milk, and honey samples with the
      linear range of 0.5-500 ng mL(-1). The method yielded limit of detection (LOD) of
      0.1 ng mL(-1) and limit of quantification (LOQ) of 0.3 ng mL(-1). The recovery of
      CAP was 97.1-101.9% from aqueous samples of environmental and food samples by the
      proposed method. Compared with liquid-liquid extraction, solvent sublation and
      ionic liquid aqueous two-phase extraction, ILATPF can not only separate and
      concentrate chloramphenicol with high sublation efficiency, but also efficiently
      reduce the wastage of IL. This novel technique is much simpler and more
      environmentally friendly and is suggested to have important applications for the
      concentration and separation of other small biomolecules.

PMID- 21168563
TI  - Synthesis of a molecularly imprinted polymer and its application for
      microextraction by packed sorbent for the determination of fluoroquinolone
      related compounds in water.
AB  - Molecularly imprinted polymer (MIP) has been synthesized by precipitation
      polymerization using ciprofloxacin (CIP) as template for the analysis of
      fluoroquinolone antibiotics (FQs). This MIP material was packed as sorbent in a
      device for microextraction by packed sorbent (MEPS) combined with liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) for the analysis of selected
      FQs drugs including CIP, norfloxacin (NOR) and ofloxacin (OFLO) in municipal
      wastewater samples. In comparison to the new MIP-MEPS procedure, the target
      compounds were also determined by solid-phase extraction (MISPE) using the new
      molecular imprinted polymer material to validate the new MIP-MEPS method. The
      ability of the MIP for molecular recognition of CIP, NOR and OFLO was proved in
      presence of structurally different environmental relevant substances such as
      quinolones (Qs), flumequine (FLU), di(methyl)phthalate (DMP), technical 4
      nonylphenol (NP), caffeine, Galaxolide((r)), Tonalid((r)), di(butyl)phthalate
      (DBP), Triclosan, bisphenol-A (BPA), carbamazepine, di(ethylhexyl)phthalate
      (DEHP), estradiol and octocrylene. The analysis of wastewater samples revealed
      the high selectivity of the synthesized polymer which was able to recognize and
      retain the target analytes by both extraction methods, the offline SPE with MIP
      material and the semi-automated MEPS packed with MIP material.

PMID- 21168564
TI  - Screening of fibrillogenesis inhibitors of beta2-microglobulin: integrated
      strategies by mass spectrometry capillary electrophoresis and in silico
      simulations.
AB  - The challenging search of ligands for the amyloidogenic protein beta(2)
      microglobulin led us to set up an integrated strategy that combines analytical
      techniques and molecular modelling. Using a chemical library composed of 90
      sulphonated molecules and a novel MS screening approach, we initially single out
      a few new binders. To check for anti-amyloid activity, the best hit obtained was
      thoroughly studied by docking analysis, affinity and refolding experiments by
      capillary electrophoresis and in vitro fibrillogenesis Thioflavin T test.
      Correlative analysis of the overall results obtained from the MS screening led to
      develop an equation able to identify the key factors of the affinity for beta(2)
      microglobulin and to predict the affinity for novel derivatives. The proposed
      equation was then used for a virtual screening of a large compound database.
      Studies on the new hit thus retrieved confirm the predictive potential of both
      the equation on affinity and of docking analysis on anti-amyloid activity.

PMID- 21168566
TI  - Are antibiotic screening approaches sufficiently adequate? A proficiency test.
AB  - A proficiency test including the screening analysis of antibiotics in beef using
      cryogenicly minced materials was organized by RIKILT in 2009. The test included
      blank beef samples and beef samples spiked with either flumequine or a
      combination of lincomycin and spectinomycin around the maximum residue limits
      [1]. The suitability of the materials was demonstrated with a homogeneity and a
      stability study. This study showed that cryogenically minced spiked muscle
      material is suited for proficiency tests aiming at the screening and the
      confirmatory analysis. Of the 26 participants, 23 carried out their in-house
      screening approach involving microbial, biochemical or instrumental methods, or a
      combination of these to cover the broad range of antibiotic groups. The false
      negative rate was 73% for microbial methods, 50% for biochemical and 22% for
      instrumental methods. These results indicate that substantial effort is needed to
      improve screening approaches and that more regular proficiency tests are needed
      to reveal the shortcomings in the currently applied screening methods.

PMID- 21168565
TI  - GC determination of N-nitrosamines by supersonic molecular beam MS equipped with
      triple quadrupole analyzer, GC/SMB/QQQ/MS.
AB  - The determination of 14 N-nitrosamines by a supersonic molecular beam electron
      ionization mass spectrometer equipped with triple quadruple analyzer,
      GC/SMB/EI/QQQ/MS is presented. The supersonic molecular beam electron ionization
      ion source allows the elucidation of the molecular ion of 13 out of the 14
      examined nitrosamines (except for diphenylnitrosamine which was degraded before
      the analysis). It was possible to use the molecular ions of all the nitrosamines
      as the parent ions for multiple reactions monitoring mode, which in turn allows
      significant increase of specificity and lowering of the method limit of detection
      of the higher molecular weight nitrosamines. The instrumental LOD for different N
      nitrosamines was 1-5 pg injection(-1). The proposed method was exemplified by
      analysis of N-nitrosamines and N-nitrosatables in rubber teats according to the
      British Standard BS EN 12868:1999.

PMID- 21168567
TI  - Screening of lipophilic marine toxins in shellfish and algae: development of a
      library using liquid chromatography coupled to orbitrap mass spectrometry.
AB  - Most liquid chromatography (LC) mass spectrometric (MS) methods used for routine
      monitoring of lipophilic marine toxins focus on the analysis of the 13 toxins
      that are stated in European Union legislation. However, to date over 200
      lipophilic marine toxins have been described in the literature. To fill this gap,
      a screening method using LC coupled to high resolution (HR) orbitrap MS
      (resolution 100000) for marine lipophilic toxins has been developed. The method
      can detect a wide variety of okadaic acid (OA), yessotoxin (YTX), azaspiracid
      (AZA) and pectenotoxin (PTX) group toxins. To build a library of toxins,
      shellfish and algae samples with various toxin profiles were obtained from
      Norway, Ireland, United Kingdom, Portugal and Italy. Each sample extract was
      analyzed with and without collision induced dissociation fragmentation. Based on
      their mass and specific fragmentation pattern, 85 different toxins were
      identified comprising 33 OA, 26 YTX, 18 AZA and 8 PTX group toxins. A major
      complication of full scan HRMS is the huge amount of data generated (file size),
      which restricts the possibility of a fast search. A software program called
      metAlign was used to reduce the orbitrap MS data files. The 200-fold reduced data
      files were screened using an additional software tool for metAlign:
      'Search_LCMS'. A search library was constructed for the 85 identified toxins. The
      library contains information about compound name, accurate mass, mass deviation
      (<5 ppm), retention time (min) and retention time deviation (<0.2 min). An
      important feature is that the library can easily be exchanged with other
      instruments as the generated metAlign files are not brand-specific. The developed
      screening procedure was tested by analyzing a set of known positive and blank
      samples, processing them with metAlign and searching with Search_LCMS. A toxin
      profile was determined for each of the contaminated samples. No toxins were found
      in the blank sample, which is in line with the results obtained for this sample
      in the routine monitoring program (rat bioassay and tandem LC-MS).

PMID- 21168568
TI  - Highly routinely reproducible alignment of 1H NMR spectral peaks of metabolites
      in huge sets of urines.
AB  - A method to obtain high reproducibility of (1)H NMR chemical shift of peaks of
      biofluid metabolites, by simple acidification with HCl is evaluated. Biofluid
      (1)H NMR analysis is indeed spoiled by a strong chemical shift dependence of
      metabolite peaks on parameters such as ionic strength, concentration of some
      earth alkali cations and, mostly, on pH of samples. The resulting chemical shift
      variations, as large as 0.1 ppm, generate misalignments of homogeneous peaks,
      artifacts and misinterpretations. Reproducible alignment is essential in (1)H NMR
      based metabonomics, where peak misalignments prevent even very wide bins (i.e.,
      0.04 ppm, as elsewhere proposed) from being used to integrate spectral data for
      multivariate statistical analysis. Here is demonstrated that routine
      acidification with HCl to 1.2<=pH<=2.0 ensures highly reproducible peak alignment
      of urine (1)H NMR spectra. In this respect, simple inspection of citrate peaks in
      the urine can be used to measure pH, as it will be extensively discussed, in that
      at such low pH they show no dependency on other urine components as reported at
      higher pH. Under these conditions, in as many as 493 urine samples, in which
      concentrations of Ca(2+), Mg(2+), K(+), Na(+), Cl(-), phosphate, and creatinine
      and ionic strength measured by means of well standardized conventional
      procedures, showed very wide ranges, peaks align within a SD always lower than
      0.002 ppm, thus allowing the use of integration bins at least five times narrower
      than 0.04 ppm.

PMID- 21168569
TI  - Determination of the nitrogen content of nitrocellulose from smokeless gunpowders
      and collodions by alkaline hydrolysis and ion chromatography.
AB  - In this work, a method to determine the nitrogen content of nitrocellulose from
      gunpowders and collodions is proposed. A basic hydrolysis of nitrocellulose with
      1.0% (m/v) NaOH at 150 degrees C during 30 min was carried out for nitrocellulose
      from gunpowders (after its previous isolation by a protocol optimized by our
      research group) and from collodion samples. The concentration of nitrate and
      nitrite ions in the hydrolysate was determined by ion chromatography with
      suppression and conductimetric detection. The nitrogen content of nitrocellulose
      was calculated from the values of the concentration of both ions. The
      quantitative method was evaluated in terms of selectivity, sensitivity,
      robustness, limits of detection and quantification, and precision, measured as
      repeatability and intermediate precision. These parameters were good enough to
      demonstrate the validity of the method and its applicability to the determination
      of the nitrogen content of nitrocellulose contained in different types of
      gunpowders (single- and double-base gunpowders, manufactured from 1944 to 1997)
      and in commercial collodion samples. For gunpowders, the nitrogen content
      determined with the optimized method was compared with the values reported by the
      official label of the ammunition (obtained by a digestion/titration method) and
      errors, by defect, ranging from 1% to 15.2% (m/m) were calculated. The highest
      errors were obtained for the oldest gunpowders and could be attributed to the
      loss of nitro groups in the nitrocellulose molecule during aging. For collodion
      samples, errors could not be calculated since the real nitrogen content for these
      samples was not given in the label. In addition, the analysis time (2h for
      nitrocellulose isolation, 1.5h for nitrocellulose hydrolysis, and 0.2h for
      chromatographic separation) was about 10 times lower than in the
      digestion/titration method nowadays used for gunpowder samples.

PMID- 21168570
TI  - Fast and simultaneous determination of phenolic compounds and caffeine in teas,
      mate, instant coffee, soft drink and energetic drink by high-performance liquid
      chromatography using a fused-core column.
AB  - A fast HPLC method with diode-array absorbance detector and fluorescence detector
      for the analysis of 19 phenolic acids, flavan-3-ols, flavones, flavonols and
      caffeine in different types of samples was developed. Using a C(18) reverse-phase
      fused-core column separation of all compounds was achieved in less than 5 min
      with an overall sample-to-sample time of 10 min. Evaluation of chromatographic
      performance revealed excellent reproducibility, resolution, selectivity and peak
      symmetry. Limits of detection for all analyzed compounds ranged from 0.5 to 211
      MUg L(-1), while limits of quantitation ranged between 1.5 and 704 MUg L(-1). The
      developed method was used for the determination of analytes present in different
      samples, including teas (black, white, green), mate, coffee, cola soft drink and
      an energetic drink. Concentration of the analyzed compounds occurring in the
      samples ranged from 0.4 to 314 mg L(-1). Caffeine was the analyte found in higher
      concentrations in all samples. Phytochemical profiles of the samples were
      consistent with those reported in the literature.

PMID- 21168571
TI  - Layered double hydroxides: a novel nano-sorbent for solid-phase extraction.
AB  - The nickel-aluminum layered double hydroxide (Ni-Al LDH) was synthesized by a
      simple co-precipitation method with controlled pH and followed by hydrothermal
      treatment. The obtained nano-structured inorganic material was employed, for the
      first time, as a new solid-phase extraction (SPE) sorbent for the extraction and
      pre-concentration of trace levels of fluoride ions from aqueous solutions. An
      indirect method was used for monitoring of extracted fluoride ions. The method is
      based on the quenching effect of extracted fluoride ions upon the fluorescence
      intensity of Al-oxine complex via the forming of AlF(6)(3-), which was determined
      spectrofluorometrically at lambda(em)=510 nm with excitation at lambda(ex)=404
      nm. The effect of several parameters such as type of interlayer anion in Ni-Al
      LDH structure, pH, sample flow rate, elution conditions, amount of nano-sorbent,
      sample volume and co-existing ions on the extraction efficiency of the analyte
      were investigated. The results showed that fluoride ions could be retained on the
      Ni-Al (NO(3)(-)) LDH at pH 6.0 and stripped by 1.2 mL of 3.0 mol L(-1) NaOH. In
      the optimum experimental conditions, the limit of detection (3s) and enrichment
      factor were 9.0 ng mL(-1) and 50, respectively. The optimized method was
      successfully applied to the determination of fluoride concentration in various
      water samples. The results obtained from the proposed method were successfully
      compared with those provided by standard SPADNS method.

PMID- 21168575
TI  - Community health centers: disparities in health care in the United States 2010.

PMID- 21168576
TI  - Building a sustainable rural health system in the era of health reform.

PMID- 21168577
TI  - Improving access to primary care and health outcomes in migrant farm worker
      populations: challenges and opportunities.

PMID- 21168578
TI  - Homelessness and health care: considerations for evaluation, management, and
      support within the primary care domain.

PMID- 21168579
TI  - Health literacy: a potential barrier in caring for underserved populations.

PMID- 21168580
TI  - Discovery of a novel biomarker in the urine in women with endometriosis.
AB  - OBJECTIVE: To investigate whether proteins secreted in urine differ between women
      with and without endometriosis. DESIGN: Laboratory study using human urine.
      SETTING: University-based laboratory. PATIENT(S): Women with and without
      endometriosis undergoing laparoscopy, hysteroscopy and curettage.
      INTERVENTION(S): Urine collection from women with and without endometriosis. MAIN
      OUTCOME MEASURE(S): Proteomic techniques and mass spectrometry to identify
      proteins secreted in the urine of women with and without endometriosis.
      RESULT(S): On average, 133 proteins were significantly different between women
      with and without endometriosis. Cytokeratin-19 was highly up-regulated in the
      urine of women with endometriosis. CONCLUSION(S): Cytokeratin-19 may be a
      valuable urinary biomarker for endometriosis.

PMID- 21168581
TI  - Short-term change in growth of uterine leiomyoma: tumor growth spurts.
AB  - OBJECTIVE: To describe the short-term changes in growth of uterine leiomyomas
      (fibroids). DESIGN: Prospective observational study. SETTING: University research
      center. PATIENT(S): Premenopausal women with fibroids (18 blacks and 18 whites)
      recruited through a physician network and community outreach. INTERVENTION(S):
      Not applicable. MAIN OUTCOME MEASURE(S): The volumes of 101 fibroids were
      measured at enrollment, 3, 6, and 12 months with magnetic resonance imaging,
      resulting in three interval-specific growth rates. Growth spurts were defined by
      interval growth rates>=30% per 3 months and substantially greater than during
      other intervals of observation. An overall measure of short-term change in
      fibroid growth was calculated as the variance of the three interval-specific
      growth rates. RESULT(S): Growth spurts were observed in 37 of the 101 fibroids, a
      prevalence nearly tenfold higher than that attributable to potential measurement
      error. Fibroids from the same woman did not have similar short-term growth, nor
      were woman-specific factors (age, race/ethnicity, parity, body mass) or the
      fibroid position in the uterus important. However, large fibroids (>5 cm
      diameter) had less short-term change than smaller fibroids. CONCLUSION(S): Short
      spurts of growth are common for fibroids, suggesting that tumor biology may
      change rapidly.

PMID- 21168585
TI  - Challenging issues of overseas transplantation in mainland China: Taiwan organ
      transplant health professionals' perspective.
AB  - OBJECTIVE: As the source of organs is limited in Taiwan, and communication
      systems are becoming more open between Taiwan and mainland China, the call for
      overseas transplantation in mainland China is increasing in Taiwan. This study
      explored the perspectives of Taiwan organ transplant health professionals on the
      challenging issues related to transplantation procedures in mainland China,
      including health professionalism as well as collaborative systems for information
      and communication technologies (ICTs). METHODS: A purposive sample including
      overseas transplant surgeons (OTS), registered nurses (RN), overseas transplant
      coordinating nurses (OTCN), and e-health ICTs experts (eh-ICTs) was obtained from
      two medical centers in Taipei. Subjects underwent face-to-face interviews with
      data subjected to content analysis. RESULTS: The 70 subjects included OTS (n =
      20), RN (n = 25), OTCN (n = 15), and eh-ICTs (n = 10). Their ages ranged from 23
      to 63 years old (mean, 33.7 years). The current challenges were identified: (a)
      lack of workable collaborative systems for continuous medical care between two
      parties due to different medical recording systems in particular (86%, n = 60;
      OTS, n = 19; RN, n = 21; OTCN, n = 10; eh-ICTs, n = 10); (b) lack of mutual
      trustworthy relationships between medical delivery systems (84%, n = 59; OTS, n =
      17; RN, n = 22; OTCN, n = 10; eh-ICTs, n = 10); (c) lack of accreditation systems
      to judge possible conflicts related to medical diagnosis and treatment protocols
      (79%, n = 55; OTS, n = 19; RN, n = 19; OTCN, n = 7; eh-ICTs, n = 10); (d)
      Taiwanese hesitation regarding the quality of transplant procedures in mainland
      China (71%, n = 50; OTS, n = 18; RN, n = 17; OTCN, n = 8; eh-ICTs, n = 7); and
      (e) stress from concerns of Taiwan medical societies about the benefits of
      collaboration with mainland China (64%, n = 45; OTS, n = 13; RN, n = 18; OTCN, n
      = 8; eh-ICTs n = 6). CONCLUSION: This discussion is still ongoing. Trapped by the
      limited organ source and confronted by multiple challenges revealed in this
      project, Taiwan societies have suggested to initiate interdisciplinary
      communication avenues. Starting with less culturally confounded issues such as
      establishing a reliable ICTs system (ie, e-health documents) may be more
      appreciated by the two parties in the near future.

PMID- 21168582
TI  - Laparoscopic transient uterine artery occlusion and myomectomy for symptomatic
      uterine myoma.
AB  - OBJECTIVE: To compare clinical outcomes of laparoscopic transient uterine artery
      ligation plus myomectomy (LTUAL) to simple laparoscopic myomectomy (LM) for
      symptomatic myomas. DESIGN: Comparative observational study. SETTING: Medical
      centers. PATIENT(S): One hundred sixty-seven patients with symptomatic myomas.
      INTERVENTION(S): Eighty-four patients underwent LTUAL and LM; 83 patients
      underwent LM only. MAIN OUTCOME MEASURE(S): Operative time, blood loss, gonadal
      hormone level, uterine artery resistance index, menorrhea, pregnancy rate, and
      recurrence rate of myoma. RESULT(S): The intraoperative blood loss in the LTUAL
      group was lower than in the LM group. The menstrual blood volume (MBV) and the
      menstrual period of the LTUAO group was unchanged after operation relative to the
      prediseased volume. No significant difference was found in the resistance index
      of the uterine artery blood flow, the recurrence rate, and the fertility rate
      between the LTUAL and LM groups. CONCLUSION(S): LTUAL and LM are a promising
      surgical treatment for symptomatic uterine myoma and did not produce any
      appreciable adverse effect on fertility.

PMID- 21168586
TI  - Caring for overseas liver transplant recipients: Taiwan primary family
      caregivers' experiences in mainland China.
AB  - INTRODUCTION: This study explores the motivations of overseas liver transplant
      recipient (OLTR) families of Taiwanese OLTR who undergo the procedure in mainland
      China. We report the waiting time to receive the transplant in mainland China as
      well as the rational and service. PATIENTS AND METHODS: This exploratory
      qualitative method reflects guided face-to-face, semistructured interviews with
      families members of OLTRs. Data were subjected to content analysis. RESULTS: We
      interviewed 19 OLTR family members (15 females and 4 males who were between 29
      and 71 years of age; mean 55.1 years) regarding 19 patients who had (17 males and
      2 females who were between 36 and 71 years of age, mean, 54.6 years). The OLTR
      underwent transplantation in three cities in mainland China: Tianjin, Shanghai,
      and Guangzhou. After arrival the average waiting time was 33.1 days. Subjects
      reported the following reasons to help patients undergo the procedure in mainland
      China: (1) it is difficult to have the procedure in Taiwan; (2) the desire to
      extend life; and ((3)) there is no domestic living donor. Seven reasons for
      serving as OLTR supportive family members were identified: (1) The role and
      obligation in the marital relationship; (2) a close bloodline relationship; (3)
      insufficient manpower; (4) an individual's availability; (5) evasion of
      responsibility by other family members; (6) compensation for inadequate caring
      efforts earlier in life; and (7) an unwillingness to disturb other relatives'
      lives. Finally, the following support for the OLTR was reported: providing
      company during medical treatment/doctor visits, food preparation, massage, daily
      assistance, medical care, and psychological support. CONCLUSIONS: Taiwanese OLTR
      family members' perspectives throughout the transplant process may provide better
      understanding of living experiences and concerns during the stages of overseas
      liver transplantation.

PMID- 21168587
TI  - National survey carried out by the Mexican Society of Transplantation in 2009
      regarding deceased-donor kidney allocation.
AB  - BACKGROUND: The Mexican Health Law stipulated that the criteria to be taken into
      account for deceased donor kidney allocation should include the following:
      "seriousness of recipient's condition, opportunity of transplant, expected
      benefits, compatibility with recipient, and all other accepted medical criteria."
      The practical application of these criteria has been perceived by several members
      of transplantation committees as allowing inequity in kidney allocation. The aims
      of this study were to learn the opinions of transplantation committees regarding
      current national allocation policies, and to obtain their opinions about the
      advantages of a point-score system. METHODS: A prepared questionnaire was
      validated with the collaboration of a team of transplantation physicians from the
      Mexican Society of Transplantation (MST). Ninety members of the Society, who
      represent transplantation groups were invited by mail to participate in the
      survey. RESULTS: We received 70 answered questionnaires, including 54 that
      represented the views of their respective internal transplantation committees. In
      agreement with the legislation and allocation policies currently in force were
      50% of responders; however, 60% believed that a point-score system for organ
      allocation should be mandatory and 75% believed that only patients without a
      possible live donor should be included on the waiting list to compete for a
      deceased donor kidney. Also, 84% believed that only patients with a complete pre
      transplant protocol, including recent viral serology, as well as clinically
      relevant pre-transplant evaluations by other specialists such as cardiology,
      psychiatry/psychology and urology should qualify for allocation of deceased donor
      organs; 76% believed that patients who compete for a deceased donor organ must
      have permanent support for immunosuppressive drugs as well as for short-term and
      long-term medical care. CONCLUSION: The answers gathered through this survey
      pointed out the necessity for continuous coordinated work between healthcare
      authorities and members of the MST to achieve the best guidelines for allocation
      of deceased donor kidneys including a point-score system.

PMID- 21168588
TI  - Efficacy of social worker role in corneal donation in two different periods.
AB  - INTRODUCTION: The Brazilian National System of Transplantation and the Ministry
      of Health in Brazil establish procedures and effective actions for occupational
      health care so that there are increasing numbers of organ and tissue donations.
      OBJECTIVE: This study analyzes the performance of social workers at the
      Intrahospital Donation of Organs and Tissues for Transplantation, Clinical
      Hospital, State University of Campinas, Brazil (CIHDOTT). METHODS: We
      retrospectively analyzed the number of potential cornea donors, effective
      donations, family refusal, and the reasons for nonimplementation of the donations
      in 2009 (period studied with the presence of social workers) compared with 2006
      (period studied without the presence of social workers). RESULTS: Data analysis
      revealed that in 2006 there were 141 potential cornea donors achieving 35 (25%)
      donations and 106 (75%) refusals. In 2009 there were 73 potential donors with 25
      (34%) donations and 48 (66%) refusals. The causes of family refusal prevalent in
      both periods were similar: 65% from indecision and 25% from the family's wishes
      to maintain the patient's body intact. CONCLUSION: The performance of social
      workers in this case was satisfactory, achieving an increase in donations and
      reducing the number of patients awaiting corneal transplantation while promoting
      their quality of life.

PMID- 21168589
TI  - At what price kidneys from complex donors while patients die on the waiting list:
      a word of caution.
AB  - More and more often living donors worldwide are used for kidney transplantation.
      The results are excellent, much better than from the deceased donors,
      disregarding the genetic disparity. Not surprisingly, living donation has not
      influenced the existing gap, and waiting lists are increasing. Live kidney
      donation technically has become a standardized, safe procedure. Many papers,
      including that from the Minneapolis Center quote follow-up results documenting
      that unilateral nephrectomy is safe. The Amsterdam Forum established criteria for
      living kidney donors. Most unfortunately, however, the continuous need for
      kidneys has led in the recent three years to the use of the so-called "complex"
      or "marginal" living donors, that is donors with metabolic syndrome. The argument
      for a continuous increase in living kidney donation, often used by transplant
      physicians, is quoted in the title of the abstract. This argument should never be
      used, especially by transplant physicians, who must consider the interests of
      both the recipient and the donor. Our own data presented at the last Congress of
      the Transplantation Society showed that moderate hypertension occurs in some
      patients. The risk of cardiovascular complications is definitely higher among
      donors with the metabolic syndrome, those with prediabetes, obesity, or mild
      hypertension. Most unfortunately there are no long-term follow-up data concerning
      such donors. They may require preemptive prophylaxis with step-wise
      interventional reno-protection and cardio-protection programs, which so far have
      not been implemented. For this reason, a Living Donor Registry is needed. It
      would allow objective assessment of the long-term risks of uninephrectomy among
      donors with metabolic syndrome. Such a registry is in operation in our country.
      Considering the use of kidney donors with the metabolic syndrome, one should
      remember a popular saying: "Be good, and if you cannot be good--be careful."

PMID- 21168590
TI  - Expanded criteria donor kidneys for younger recipients: acceptable outcomes.
AB  - INTRODUCTION: European senior programme (ESP) is well known for acceptable
      outcomes using expanded criteria donor (ECD) kidneys from donors older than 65
      years for recipients older than 65 years. The incidence of end-stage renal
      disease (ESRD) is 229/million in India with a mean age of 45 years. We performed
      a retrospective analysis of transplantation of ECD versus standard criteria donor
      (SCD) kidneys into younger recipients. METHODS: Forty-three ECD transplantations
      among 158 deceased donor organ transplantation (DDOT) were performed between
      January 2006 and December 2009. Among 43 transplantation from 30 donors, 14 were
      dual kidney transplantations (DKT) performed based upon biopsy evaluation. All
      recipients received thymoglobulin (rATG) induction followed by immunosuppression
      with a steroid, mycophenolate mofetil (MMF), and a calcineurin inhibitor.
      Statistical analysis used chi-square test and unpaired Student t test. Kaplan
      Meier curves were used for survival analysis. RESULTS: For ECD the mean donor age
      was 64 +/- 11 years. Cerebrovascular accidents (CVA) were the cause of death
      among 60% of donors, 73.13% of whom were hypertensive and 23.13% diabetic. Mean
      DKT donor age was 75 +/- 9.17 years versus 60 +/- 8.0 years for single kidney
      transplantation (SKT). Mean recipient age of DKT versus SKT was 44 +/- 12.4 years
      versus 43 +/- 14 years. Mean serum creatinine (SCr; mg/dL) of SKT patients was
      1.64 +/- 0.75 versus 1.68 +/- 0.46 in DKT. Mean follow-up was 455 +/- 352 days.
      Mean SCr of 43 ECD recipients of mean age, 43.4 +/- 14.2 years was 1.61 +/- 0.61
      mg/dL. Among 43 recipients, 23.25% were diabetic, 41.86% displayed delayed graft
      function (DGF), and 23.25% experienced biopsy-proven acute rejection (BPAR).
      Patient survival rate was 72.09% and graft survival rate was 67.44%. For SCD
      transplantations (n = 115), the mean donor age was 36 +/- 14 years and recipient
      mean age was 32.8 +/- 14.07 years. Mean SCr was 1.32 +/- 0.46 mg/dL with 26.95%
      recipients displaying DGF, whereas 20.86% had BPAR. In the SCD group the patient
      survival rate was 79.13% and the graft survival rate was 72.17%. Thus, although
      the ECD group showed poor graft function (P = .042), they had acceptable patient
      and graft survivals (P = .34 and P = .56, respectively). CONCLUSION: Because of
      the organ shortage, DDOT using ECD transplants for younger recipients is a
      feasible option with acceptable outcomes.

PMID- 21168591
TI  - Utilization of elderly kidney donors (>70 years) does not affect graft survival
      in the medium term.
AB  - BACKGROUND: The need for organs for renal transplantation has encouraged the use
      of grafts from increasingly older donors. Earlier studies performed in Spain have
      shown the suitability of donors aged 60-65 years. In this single-center study, we
      evaluated our results using donors >70 years old. METHODS: We evaluated 401
      primary transplantations performed from January 2000 to December 2009. Their
      initial immunosuppression was a tacrolimus-based (n = 324), cyclosporine-based (n
      = 70) or calcineurin inhibitor-free (n = 7) regimen patients. Recipients were
      classified according to the donors age: <50 (42.6%); 50-70 (39.7%) and >70
      (17.5%) years. RESULTS: There were no differences in recipient or donor gender,
      time on dialysis, cold ischemia, delayed graft function, or acute rejection
      episodes. However, the mean age was higher among patients who received grafts
      from donors >70 years old; 42.5 +/- 12.4 years for <50, 58.1 +/- 8.2 years for 50
      70, and 65.7 +/- 7.2 years for >70; (P = .000). The serum creatinine at 12 months
      was increased according to the age of the donor; 1.4 +/- 0.6, 1.8 +/- 0.6, 70 and
      1.7 +/- 0.5 mg/dL, respectively (P = .001). The graft survival rates at 5 years
      were 81%, 74%, and 70%, respectively (P = .519). Upon multivariate analysis only
      HLA-DR mismatches, delayed graft function, and acute rejection episodes were
      associated with graft loss. Patient survival rates (86%) at 5 years were similar
      among recipients from donors aged 50-70 and >70 years, but higher (96%) for those
      who received a graft from a donor <50 years (P = .003). CONCLUSIONS: Nearly 20%
      of donors were >70 years old in our study. Their kidneys displayed excellent
      short-term outcomes.

PMID- 21168592
TI  - Is estimated donor glomerular filtration rate before death a better predictor of
      decreased-donor kidney function?
AB  - The worldwide shortage of deceased-donor kidneys for transplantation has become a
      serious issue in the past decade, leading to study of marginal donors. However,
      both the availability and the utility of kidneys from deceased donors are still
      unclear. The aim of the present study was to evaluate another method to estimate
      donor kidney function rather than using donor creatinine (Cr). We studied 129
      recipients of deceased-donor kidneys from Maastriche donor categories III and IV.
      We analyzed donor Cr levels before death and recipient Cr levels at 1 year after
      transplant, as well as estimated glomerular filtration rates (eGFR). There was no
      significant difference in donor Cr levels at admission to the hospital and before
      death according to eGFR at 1 year after transplantation: <30 mL/min/1.73 m(2)
      versus ?30 mL/min/1.73 m(2). However, recipients whose donors showed lower
      average eGFR levels on admission displayed better renal function at 1 year after
      transplant (P = .025). In conclusion, donor Cr levels before death was a less
      useful measurement to relate to recipient renal function; eGFR provided a better
      index.

PMID- 21168593
TI  - Computed tomographic angiography and perfusion in the diagnosis of brain death.
AB  - INTRODUCTION: According to Polish brain death (BD) criteria, instrumental
      confirmatory tests should be used in certain clinical situations, particularly
      any case for which clinical examinations seem inadequate. Electrophysiological
      tests are often unavailable. Therefore, cerebral perfusion testing is the method
      of choice with four-vessel digital subtraction angiography (DSA), the gold
      standard. Unfortunately, DSA is an expensive and invasive examination that
      requires an experienced neuroradiologist and the availability of an angiography
      suite. Recently, multirow computed tomographic devices became available, even in
      smaller hospitals in Poland. Despite this fact, computed tomographic angiography
      (CTA) and computed tomographic perfusion (CTP) are not accepted in BD diagnosis
      protocols in Poland because of limited experience and a lack of widely accepted
      criteria. In this situation, we started a multicenter trial to determine the
      accuracy of CTA and CTP to confirm BD. METHODS: We examined 24 patients who
      fulfilled standard clinical BD criteria. We recognized the absence of brain
      perfusion in CTA examination following the criteria proposed by the French
      Society of Neuroradiology, namely, the absence of opacification of M4 middle
      cerebral artery segments (M4-MCA) and of deep cerebral veins. RESULTS: In all of
      our patients, CTA showed absence of opacification of M4 segments and of deep
      cerebral veins. In addition, three patients had CTA showing weak opacification of
      A2 segments of the anterior cerebral artery (A2-ACA) and M2 or M3-MCA.
      Opacification of the basilar artery or of the posterior cerebral arteries was not
      noted in any case. In all patients, CTP revealed zero values of regional cerebral
      blood volume and regional cerebral blood flow. Conventional angiography confirmed
      cerebral circulatory arrest in all 24 cases. CONCLUSION: CTA and CTP seem to be
      promising radiological examinations for the diagnosis of BD. They may be
      noninvasive alternatives to conventional cerebral angiography, and to the other
      instrumental confirmatory tests, that are unavailable or inadequate.

PMID- 21168594
TI  - Comparable outcomes in donation after cardiac death and donation after brainstem
      death: a matched analysis of renal transplants.
AB  - Donation after cardiac death (DCD) donors provide a valuable source of grafts for
      renal transplantation. They are exposed to an initial warm ischemic insult, which
      can affect early function. We sought to compare our initial DCD experience in
      renal transplantation with a case-matched donation after brain death (DBD) cohort
      from the same period. We included all DCD transplantations in the first 5 years
      of the program. A control DBD group was matched with a variety of donor and
      recipient factors. We demonstrated a significantly increased early dysfunction
      (DGF and primary nonfunction). DCD graft function was poorer than the DBD
      equivalent at 1- and 3-years. However, medium-term recipient and graft outcomes
      were comparable. DCD grafts continue to play a vital role in renal
      transplantation despite evidence of early graft dysfunction.

PMID- 21168595
TI  - Predicting donor asystole following withdrawal of treatment in donation after
      cardiac death.
AB  - Donation after cardiac death donation allows donor pool expansion. The period
      between withdrawal of treatment and donor a systole is extremely variable; its
      prolongation often results in unsuccessful organ procurement. We sought to assess
      a variety of donor variables to determine whether they predicted successful organ
      retrieval. We included all Donation after Cardiac Death (DCD) retrievals between
      2002 and 2009, which were grouped as successful (n = 104) versus unsuccessful (n
      = 42). Factors that predicted unsuccessful organ procurement included older donor
      age, donor history of hypertension, higher at withdrawal, and absence of
      inotropic support. On multivariate analysis, mean arterial pressure retained its
      significance. Prediction of withdrawal-to-asystole time is complex, but our
      analysis suggested that donor blood pressure at withdrawal is an important
      predictor of whether retrieval would be successful.

PMID- 21168596
TI  - Impact of cold ischemia on renal transplant outcomes following donation after
      cardiac death.
AB  - Donation after cardiac death (DCD) provides grafts in renal transplantation but
      is associated with increased early graft dysfunction. Cold ischemia time (CIT) is
      a factor that is thought to affect outcomes in renal transplantation. We sought
      to assess the impact of the length of CIT among our DCD cohort of renal
      transplants performed between April 2002 and December 2009. Since the median CIT
      was 15.5 hours, we formed two groups CIT < 15.5 (n = 100) and CIT > 15.5 hr (n =
      98). We demonstrated an increased incidence of DGF among the extended CIT group,
      but the long outcomes and the mean graft function were otherwise comparable. In
      conclusion, CIT affects early graft function; every effort should be made to
      minimize it in renal transplantation using DCD kidneys.

PMID- 21168597
TI  - Impact of age matching of donors to recipients on renal transplant outcomes
      following donation after cardiac death.
AB  - Organ donation after cardiac death (DCD) provides a valuable supply of grafts for
      renal transplantation. Age matching of donors to recipients is often used. We
      sought to determine the impact of age matching on the outcomes among our cohort
      of DCD renal transplant recipients. Using our institutional database, we gathered
      information on all DCD renal transplants performed between April 2002 and
      December 2009. We divided the cohort into two groups based upon the
      donor:recipient age ratio: age-matched (between 25th and 75th percentiles, n =
      99) and non-age-matched (<25th percentile and >75th centile, n = 100). We failed
      to demonstrate any significant difference between the two groups in terms of
      early complications or long-term outcome or function. Age matching did not appear
      to affect graft outcomes, particularly for young donors, but may have a role in
      older donors.

PMID- 21168598
TI  - Kidney injury molecule-1 correlates with kidney function in renal allograft
      recipients.
AB  - INTRODUCTION: KIM-1 (kidney injury molecule-1) is responsible for the clearance
      of debris from damaged renal tubules. KIM-1 can be expressed and excreted in
      urine within 12 hours after the initial ischemic insult and before regeneration
      of the epithelium, persisting over time thereafter. Urinary KIM-1 has been
      reported to be a noninvasive, rapid, sensitive, and reproducible biomarker of
      experimental nephrotoxic and ischemic acute kidney injury. Renal KIM-1 expression
      is significantly increased in human kidney tissue among patients with a wide
      range of kidney diseases, including various types of glomerulonephritis, chronic
      allograft nephropathy, acute rejection, hypertension, and Wegener's
      granulomatosis. Both renal and urinary KIM-1 correlate with kidney damage and
      negatively with renal function, but not with proteinuria. The aim of this study
      was to assess whether urinary KIM-1 correlated with kidney function in kidney
      allograft recipients. METHODS: Serum NGAL, creatinine and estimated glomerular
      filtration rate (eGFR) were evaluated in 170 kidney allograft recipients on
      therapy with a calcineurin inhibitor plus mycophenolate mofetil or azathioprine
      and prednisone as well as in healthy volunteers. KIM-1 was estimated in urine
      using a commercially available kit. RESULTS: Kidney transplant recipients showed
      significantly higher KIM-1 values than the control group. Normotensive kidney
      allograft recipients displayed significantly lower NGAL results than hypertensive
      subjects. Urinary KIM-1 was significantly higher among diabetic than nondiabetic
      subjects, whereas creatinine did not differ significantly between them. Upon
      univariate analysis urinary KIM-1 strongly correlated with serum creatinine (r =
      .64) and eGFR (r = -.71), and only weakly with other parameters. Upon multiple
      regression analysis, the best predictor of urinary KIM-1 was eGFR (beta -0.61),
      which explained 61% of KIM-1 concentrations. CONCLUSION: Even a successful kidney
      transplantation is associated with kidney injury as reflected by elevated urinary
      KIM-1 and lower eGFR. Therefore, KIM-1 needs to be investigated as a potential
      early marker for impaired renal function/kidney injury, especially in patients
      with other risk factors for damage such as hypertension or diabetes.

PMID- 21168599
TI  - Sequential transplant of paired kidneys following donation after cardiac death:
      impact of longer cold ischemia time on the second kidney on graft and patient
      outcome.
AB  - The United Kingdom has no national sharing scheme for kidneys received from
      donation after cardiac death (DCD). Therefore, both kidneys retrieved by a
      transplant team are implanted at a single unit, often sequentially. This study
      analyzes the impact of a prolonged cold ischaemia time on the second transplanted
      kidney and the effects on short-term and long-term outcomes in all our DCD renal
      implants from 2002 to 2009. Cold ischaemia time was significantly longer with the
      second kidney (P = .04) as was delayed graft function (P = .02). Acute rejection
      was increased in the first transplanted kidney (P < .001). Five-year patient
      survival was comparable between groups, but 5-year graft survival was higher in
      the second transplanted group (P = .04). The results confirm that, provided
      recipient centers are willing to accept higher initial rates of delayed graft
      function, it is acceptable to transplant DCD grafts sequentially without
      jeopardizing long-term graft or recipient outcome.

PMID- 21168600
TI  - Outcomes following renal transplantation after multiorgan retrieval versus kidney
      only retrieval in donation after cardiac death donors.
AB  - With the increase of donation after cardiac death (DCD) now including
      procurements for not only kidney but also liver, pancreas, and lung
      transplantations, we analyze whether multiorgan DCD retrievals have a negative
      impact on immediate and short-term renal transplant outcomes due to increased
      length of time of explantation of the kidney from the donor and the associated
      risks of re-warming. We performed a retrospective study of all DCD donors from
      2002 to 2009 at a single unit. Immediate and short-term outcomes between kidney
      only versus multiorgan retrieval were compared. Cold ischaemia was significant
      between the two groups (P = .04), but all other variables were nonsignificant.
      The results show that immediate graft function, rates of acute rejection and
      graft/recipient survival are comparable when DCD allografts are procured from
      both multiorgan and kidney-only donors. The comparable outcomes from kidney-only
      and multiorgan donations in this study may be due to by the highly selective use
      of donors for multiorgan DCD donation. This selectivity may explain the "better"
      quality of kidney for these cases in which patients were able to tolerate
      potentially injurious rewarming.

PMID- 21168601
TI  - Renal transplantation following donation after cardiac death: impact of duration
      from withdrawal to asystole.
AB  - Donation after cardiac death (DCD) allows for expansion of the donor pool,
      however, the process for DCD donation can lead to a donor's physiological
      instability before asystole. This may have a detrimental effect on graft and
      patient outcomes. We analyzed all 201 DCD donations at our unit from 2002 to 2009
      and compared short versus long durations to asystole around the median time (20
      min). Delayed graft function was comparable between the groups (P = .13), primary
      nonfunction was increased in the long duration to asystole group (P < .0001), and
      acute rejection was increased in the short duration group (P < .001). Five year
      patient survival was comparable (P = .6). In conclusion, long duration asystole
      may have an immediate effect on graft survival, but it has no overall detrimental
      effect on longer-term outcomes. Further studies are required to investigate the
      acceptable time to wait from withdrawal to asystole.

PMID- 21168602
TI  - Pulsatile perfusion of kidney allografts with Celsior solution.
AB  - BACKGROUND: Use of pulsatile perfusion (PP) to optimize outcomes in deceased
      donor renal transplantation remains controversial. This prospective analysis
      describes all cadaveric renal allografts transplanted at our center that were
      preserved with PP using Celsior solution. METHODS: We used the LifePort Kidney
      Transporter (Organ Recovery Systems) perfusion machine. Study outcomes included 1
      year graft and patient survivals as well as rates of delayed graft function and
      need for posttransplant dialysis. RESULTS: Graft survival for PP was 90% and
      patient survival 100%. The incidences of delayed graft function was 10% and of
      posttransplant dialysis, 10%. CONCLUSION: These data support the use of PP with
      Celsior solution.

PMID- 21168603
TI  - Perfusion using oxygenated buffer containing prostaglandin E1 before cold
      preservation prevents warm ischemia-reperfusion injury in liver grafts from non
      heart-beating donors.
AB  - We have previously reported that perfusion using warm oxygenated buffer before
      cold preservation (preperfusion) improved the viability of liver grafts from non
      heart-beating donors. We demonstrated that adenosine triphosphate content was
      restored and apoptosis was reduced. The objective of the present study was to
      evaluate mitochondrial functions after this preperfusion and the effects of
      addition of prostaglandin E(1) (PGE(1)) to the preperfusion buffer. Preperfusion
      improved portal flow, bile production, and mitochondrial function, and reduced
      alanine aminotransferase levels in the perfusate. Addition of PGE(1)
      significantly increased bile production and suppressed alanine aminotransferase
      and tumor necrosis factor-alpha levels. PGE(1) minimized mitochondrial membrane
      damage and ischemic injury after liver graft reperfusion. Release of
      mitochondrial cytochrome c was suppressed by addition of PGE(1). In conclusion,
      perfusion using oxygenated buffer containing PGE(1) before cold preservation
      significantly prevented cellular damage, protected mitochondrial function, and
      suppressed the release of mitochondrial cytochrome c in livers undergoing warm
      ischemia-reperfusion injury. This method shows promise for reducing cellular
      damage in non-heart-beating donor liver grafts.

PMID- 21168604
TI  - Induction of different types of cell death after normothermic liver ischemia
      reperfusion.
AB  - Normothermic liver ischemia-reperfusion (I-R) may induce hepatocellular
      autophagy, apoptosis, and necrosis. The aim of this study was to investigate
      these three types of cell death in normothermic liver I-R in rats. A segmental
      normothermic ischemia of the liver was induced for 120 minutes. Liver autophagy
      was evaluated by transmission electron microscopy and LC3 (Light Chain 3)
      immunohistochemical studies. Liver apoptosis was assessed by FLIVO (FLuorescence
      in vIVO) and TUNEL (TdT-mediated dUTP nick end labeling) assays. Liver necrosis
      was determined by optical microscopic examination. Autophagy was increased in
      ischemic liver lobes at 6 hours after reperfusion, compared with nonischemic
      lobes. Fluorescence microscopy showed in situ caspase-3 and -7 specific activity
      to be increased in ischemic liver lobes after 6 hours of reperfusion, compared
      with nonischemic lobes. Quantitative analysis of apoptotic cells evaluated by the
      TUNEL method showed a clearly significant increase in ischemic liver lobes at 6
      hours after reperfusion, compared with nonischemic lobes. Necrotic cell death was
      significantly increased in ischemic liver lobes at 6 hours after reperfusion,
      compared with nonischemic lobes (P < .005). In conclusion, 120 minutes
      normothermic liver I-R resulted in increased autophagic, apoptotic and necrotic
      cell death.

PMID- 21168605
TI  - The effect of HTK solution modification by addition of prolactin on biochemical
      indices reflecting ischaemic damage to porcine kidney.
AB  - INTRODUCTION: The aim of our study was to evaluate the impact of perfusion with
      HTK solution, modified by the addition of prolactin (PRI), on selected
      biochemical parameters of porcine renal damage within 24 and 48 hours after the
      onset of cold ischemia time. METHODS: Each study group consisted of 10 adult
      pigs. During harvesting the kidneys were rinsed with Ringer's solution (group 1),
      HTK (group 2), and HTK+PRL in a dose of 0.2 mg/dL, 0.02 mg/dL, and 0.01 mg/dL in
      groups 3, 4 and 5, respectively. The levels of lactate dehydrogenase, asparagine
      (AST) and alanine aminotransferases, lactates, total protein, potassium and
      calcium were determined in the perfusate. After 24 and 48 hours the rinsing
      procedure and the abovementioned tests were repeated. RESULTS: After 24 hours of
      storage, in 4 groups, significantly lower levels of LDH (U/L) were recorded
      compared with HTK solution alone, namely 235 +/- 93 versus 271 +/- 125 (perfusion
      minute, 0), and 55 +/- 21 versus 125 +/- 94 (30th minute). Similar behavior
      pattern was presented by AST (U/L) and potassium (mmol/L), and the results were
      31 +/- 8 versus 35 +/- 12 and 16 +/- 10 versus 29 +/- 14, and 12 +/- 3 versus 16
      +/- 3 and 10 +/- 1 versus 13 +/- 1, respectively. The changes described above
      were not observed in the 48th hour of reperfusion. CONCLUSION: Our study results
      indicate the possibility of cytoprotective action of PRL after adding it to the
      fluid perfusing kidneys during cold ischemia. This effect, observed after 24
      hours of storage, was to a considerable extent dose dependent. In our experiment
      the effect was pronounced only at 0.02 mg/dL supply of PRL.

PMID- 21168606
TI  - Effect of FTY720 treatment on postischemic pancreatic microhemodynamics.
AB  - CD4+ T cells contribute to disturbances of pancreatic microcirculation after cold
      and even after warm ischemia/reperfusion (I/R). The aim of this study was to
      investigate a possible protective role of FTY720 (fingolimod) in this setting. In
      an in vivo model (42 Wistar rats), ischemia of the pancreas was induced for 60
      minutes under anesthesia with xylazin/ketanest. Sham-operated (SO) (I), untreated
      ischemic (II), and treatment group with FTY720 pre-treatment (1 mg/kg body weight
      i.v.) (III) were investigated. The effect of FTY720 on I/R injury was assessed by
      in vivo microscopy 30-90 minutes after reperfusion and by measurement of serum
      lipase. In the untreated ischemic group (II), capillary constriction to 85.3 +/-
      6.3% of SO diameters and a reduction of functional capillary density to 67% was
      found. After 30 minutes of reperfusion, the number of T cells in capillaries was
      increased (165.7%; P < .05 vs I). FTY720 pretreatment reduced this number to
      54.2% of SO (P < .05 vs II). Likewise, the number of adherent leukocytes in
      capillaries (145.4 +/- 11.2% of SO) was reduced in group III (109.3 +/- 11.4%; P
      < .05 vs II), leading to an improvement in functional capillary density in the
      treatment group (98.2 +/- 2% of SO; P < .05 vs II). According to improved
      microcirculation, lipase values were reduced in the therapy group (P < .05). In
      conclusion, FTY720 ameliorates the microcirculatory and biochemical
      manifestations of pancreatic I/R injury by preventing T-cell infiltration.

PMID- 21168607
TI  - Acceptable residual renal function after retroperitoneoscopic kidney donation in
      elderly donors.
AB  - Recent studies suggest that the overall survival and risk of end-stage renal
      disease among renal transplant donors are similar to those of the general
      population, but few studies focused on elderly donors. Among 88 donors who
      underwent retroperitoneoscopic live donor nephrectomies; 20 (22.7%) were elderly,
      namely, older than 65 years. Perioperative characteristics, such as sex, donor
      kidney side (left or right), body mass index, operative time, blood loss, and
      complication rate were not significantly different among groups classified by
      age: young (<50), middle (50-65), or elderly (>65). One month after kidney
      donation, the serum, creatinine values in the young, middle, and elderly groups
      increased to 1.05 +/- 0.25, 0.96 +/- 0.24, and 1.06 +/- 0.15 mg/dL (P = .103) and
      the estimated glomerular filtration rate (eGFR) decrease to 63 +/- 10, 63 +/- 14,
      56 +/- 8 mL/min/1.73 m(2), respectively (P = .037). At three months and at three
      years after donation these parameters showed the same degree of improvement in
      all groups. Percentage of eGFR (% eGFR) of its pre-donation value in the young
      and middle groups improved up to 21% and up to 9%, respectively, until four years
      after donation, whereas that of the elderly group remained unchanged below 1%. In
      conclusion residual renal function after retroperitoneoscopic kidney donation in
      elderly donors was stable and acceptable during mid-term observation. Our
      retroperitoneoscopic approach was safe.

PMID- 21168608
TI  - One hundred six live kidney donors in a single German transplantation center:
      renal, physical, and psychological follow-up.
AB  - OBJECTIVE: The objective of this study was to analyze the psychological and
      physical status as well as renal outcomes of 106 live kidney donors between 1993
      and 2003. METHODS: We performed general and nephrological examinations, including
      measurements of creatinine clearance (ClCr), proteinuria, and 24-hour blood
      pressure monitoring. We evaluated the psychological and general health situation
      using the standardized SF-36 questionnaire. RESULTS: We evaluated 69/106 (65%)
      live kidney donors at 5.3 +/- 0.4 years after donation. The reason for the 37
      drop-outs were unknown current address (n = 21), refusal of study participation
      (n = 14), and death due to accident and suicide (n = 2). In the 69 donors renal
      function was well preserved: serum creatinine 1.3 +/- 0.0 mg/dL; ClCr 81 +/- 2
      mL/min; postdonation to predonation ClCr ratio 0.73 +/- 0.02; and proteinuria 104
      +/- 11 mg/d. None of the donors experienced renal failure, although 36/69 (52%)
      patients have developed de novo hypertension. Compared with normotensive donors,
      the hypertensive subgroup was significantly older at the time of donation (50.7
      +/- 1.4 vs 46.4 +/- 1.6 years; P = .010) and had a longer interval since donation
      (6.4 +/- 0.2 vs 3.9 +/- 0.1 years; P = .001). SF-36 questionnaire results in live
      kidney donors showed higher scores regarding physical (54.3 +/- 0.8 vs 49.3 +/-
      0.1; P = .048) and psychological health (53.8 +/- 0.6 vs 50.7 +/- 0.1; P = .043)
      compared with the average German population. CONCLUSION: Our cohort of live
      kidney donors showed good renal outcomes and superior SF-36 scores in both
      physical and psychological health compared with the German population. The risk
      of de novo hypertension increased with age and time after donation. Blood
      pressure screening should be regularly performed especially in the long term
      after donation.

PMID- 21168609
TI  - Effect of renal transplantation on visual evoked potential abnormalities of
      chronic renal failure.
AB  - BACKGROUND: Cranial neuropathies including optic nerve involvement are well-known
      complications of chronic renal failure (CRF), but most clinicians often do not
      follow the progression of these damages during course of CRF or their
      reversibility after treatment. So, this study evaluates effects of renal
      transplantation on visual system functions using visual-evoked potentials (VEP).
      METHODS AND MATERIALS: Forty CRF transplantation candidates and 40 control
      healthy persons underwent VEP before transplantation. VEP was repeated 3 months
      later for patients who had successful grafts. RESULTS: None of recorded VEP
      changes were significant in our study, although the absolute number of normal
      parameters increased after transplantation. In patients who had less than 1 year
      duration of CRF, more positive changes were observed after transplantation (p <
      .05). CONCLUSION: Our study showed the VEP changes were not significant. This may
      have been due to the delay in transplantation. CRF duration had a significant
      effect on almost all parameters of VEP which means that the longer duration of
      CRF lead to a decreased probability of VEP changes to return to normal after
      transplantation.

PMID- 21168610
TI  - Desensitization protocol in highly HLA-sensitized and ABO-incompatible high titer
      kidney transplantation.
AB  - BACKGROUND: A positive crossmatch indicates the presence of donor-specific
      alloantibodies and is associated with a graft loss rate of >80%; anti-ABO blood
      group antibodies develop in response to exposure to foreign blood groups,
      resulting in immediate graft loss. However, a desensitization protocol for highly
      HLA-sensitized and ABO-incompatible high-titer kidney transplantation has not yet
      been established. METHODS: We treated 6 patients with high (>=1:512) anti-A/B
      antibody titers and 2 highly HLA-sensitized patients. Our immunosuppression
      protocol was initiated 1 month before surgery and included mycophenolate mofetil
      (1 g/d) and/or low-dose steroid (methylprednisolone 8 mg/d). Two doses of the
      anti-CD20 antibody rituximab (150 mg/m(2)) were administered 2 weeks before and
      on the day of transplantation. We performed antibody removal with 6-12 sessions
      of plasmapheresis (plasma exchange or double-filtration plasmapheresis) before
      transplantation. Splenectomy was also performed on the day of transplantation.
      Postoperative immunosuppression followed the same regimen as ABO-compatible
      cases, in which calcineurin inhibitors were initiated 3 days before
      transplantation, combined with 2 doses of basiliximab. RESULTS: Of the 8
      patients, 7 subsequently underwent successful living-donor kidney
      transplantation. Follow-up of our recipients showed that the patient and graft
      survival rates were 100%. Acute cellular rejection and antibody-mediated
      rejection episodes occurred in 1 of the 7 recipients. CONCLUSIONS: These findings
      suggest that our immunosuppression regimen consisting of rituximab infusions,
      splenectomy, plasmapheresis, and pharmacologic immunosuppression may prove to be
      effective as a desensitization protocol for highly HLA-sensitized and ABO
      incompatible high-titer kidney transplantation.

PMID- 21168612
TI  - Functional status of hemodialysis arteriovenous fistula in kidney transplant
      recipients as a predictor of allograft function and survival.
AB  - There is no accepted policy for preserving or ligating arteriovenous fistula
      (AVF) after successful kidney transplantation. The aim of this study was to
      compare kidney graft function and survival between patients with a functional AVF
      at 1 year after-transplantation with those having a nonfunctional AVF. This
      historical cohort study included 311 kidney transplant recipients between January
      2000 and December 2008 with a functional AVF at the time of transplantation.
      Patients were divided into 2 groups according to functional status of AVF at 1
      year after transplantation. Graft function was assessed at 1 year by serum
      creatinine and estimated glomerular filtration rate (eGFR) using the 4-variable
      Modification of Diet in Renal Disease formula. Kaplan-Meier and Cox proportional
      hazards analyses were used to assess the relationship between the functional
      status of the AVF and graft survival. The 311 recipients had a mean age of 47 +/-
      11 years (range, 14 to 70) with 188 (60.5%) males. Patients with functional AVF
      at 1 year (n = 239) showed higher serum creatinine and lower eGFR values than
      those with nonfunctional AVF (n = 72): namely 110 +/- 38 MUmol/L and 69 +/- 21
      mL/min/1.73 m(2) versus 99 +/- 30 MUmol/L and 74 +/- 19 mL/min/1.73 m(2),
      respectively (P < .05). Persistence of a functional AVF at 1 year after
      transplantation was associated with a greater incidence of eGFR <60 mL/min/1.73
      m(2) compared with nonfunctional AVF: 36.8% versus 23.6% (odds ratio, 1.885; 95%
      confidence interval [CI], 1.031-3.450; P = .038). The 5-year allograft survival
      rates were 60% among patients with a functional AVF versus 75% among those with a
      nonfunctional AVF (P = .045). The adjusted analyses revealed the persistence of a
      functional AVF to be associated with an increased risk for future allograft loss
      (hazard ratio, 1.336; 95% CI, 1.018-1.755; P = .037). In conclusion, the
      persistence of a functional AVF was associated with a lower eGFR at 1 year after
      transplantation and an increased risk for future allograft loss.

PMID- 21168611
TI  - Impact of pretransplant intravenous immunoglobulin administration on anti-AB0
      antibody levels in AB0-incompatible living donor kidney transplantation.
AB  - BACKGROUND: From March 2007 to July 2010, we performed 14 AB0-incompatible (AB0i)
      living kidney transplantations using donor blood group-specific immunoadsorption
      (IA), anti-CD20 monoclonal antibody, and intravenous immunoglobulin (IVIG)
      pretreatment. METHODS: To analyze the effect of a presumed anti-donor blood group
      specific antibody transfer by IVIG administration (0.5 g/kg; 5.4 +/- 0.9 days
      pretransplant), we assessed AB0i antibody titers in different IVIG preparations
      and evaluated their impact on patient AB0i antibody titers. RESULTS: AB0i
      antibody IgG titers before treatment ranged from 8 to 1024. We performed 6.9 +/-
      1.1 IA procedures pretransplant to reach AB0i antibody titers <=4, which enabled
      successful transplantation in all pretreated patients. Their mean serum
      creatinine at discharge was 1.5 +/- 0.1 mg/dL. IVIG preparations differed
      profoundly in their AB0i antibody titers: The lowest titers were observed in
      Sandoglobulin preparations (1-8) compared with Intratect (2-128), Octagam (4-32)
      and Gamunex (2-512). Usually, administration of the IVIG preparation containing
      the lowest isoagglutinin titer resulted in low AB0i antibody titer increments in
      patient sera: Sandoglobulin, 2 titer steps (n = 2), 1 titer step (n = 1), and 0
      titer steps (n = 5). In contrast, Octagam showed 0 titer steps (n = 2) and
      Intratect, 0 titer steps (n = 3). However, after Gamunex administration, the AB0i
      antibody titer of 8 and the AB0i antibody titer rose 3 titer steps (16 to 128; n
      = 1), which could not be explained by passive transfer of isoagglutinin alone.
      CONCLUSION: Our data showed that the choice of IVIG preparation with the lowest
      AB0i antibody levels is a time- and cost-sparing step in the pretreatment of AB0i
      living donor kidney recipients. Posttransplant, a high isoagglutinin content
      within the IVIG preparation has the potential to induce antibody-mediated
      rejection.

PMID- 21168613
TI  - New registry and tracking system for renal transplantation in Japan.
AB  - Following The Declaration of Istanbul 2008, a registration committees of The
      Japan Society for Transplantation and The Japanese Society for Clinical Renal
      Transplantation planned to establish a new registry and tracking system for renal
      transplant recipients and donors supported by a Health Labor Sciences Research
      Grant by The Ministry of Health Labour and Welfare. In place of the previous
      paper-based system, we established the new registry and tracking system, JARTRE
      (Japan Renal Transplantation Registry), using USB memory in 2009. Recipient and
      donor data were inputted into the USB memory at the transplantation centers. The
      memory was reviewed a yearly by committees. The recipient and donor registration
      included details from both. The tracking is performed centrally 3 months, 1 year,
      and every year after the operation. The advantages of this system are the ease of
      input, adequacy of the data, and rapid statistical processing. In 2009, we
      registered 97.9% of new renal transplantation recipients and donors; in 2008 it
      was more than 81.9% of all past renal transplantation recipients in Japan.

PMID- 21168614
TI  - Different etiologies of graft loss and death in Asian kidney transplant
      recipients: a report from Thai Transplant Registry.
AB  - BACKGROUND: Kidney transplantation is the most performed solid organ
      transplantation in Thailand. Over 4000 patients have received kidney
      transplantation from 23 centers within the kingdom. This study sought to
      demonstrate the causes of graft loss and death in Thai patients receiving kidney
      transplant during the past decade. PATIENTS AND METHODS: The Thai Transplant
      Registry database was used to evaluate the causes of graft loss and death. This
      database was established since 1997, a total of 2298 kidney transplants were
      available for analysis. Graft loss was defined as return to dialysis, graft
      removal, retransplantation, or death of the recipients. Patient survival was
      analyzed by all deaths. RESULTS: Among 2298 recipients, 59% received organs from
      deceased donors. The mean age at transplantation was 42 years (SD 12) and 61%
      were male. The most common identified causes of the end-stage renal disease were
      chronic glomerulonephritis (25.3%) and hypertensive nephropathy (11.3%); half of
      those were unknown. Actuarial graft survival rates at 1 and 5 years were 89% and
      73%, respectively. The common causes of graft loss were chronic allograft
      nephropathy (53%), acute rejection (15%), death with a functioning graft (15%),
      and transplant renal artery diseases (7%). The greatest proportion (64%) of
      deaths was infection owing to septicemia and/or pulmonary infection. The others
      were from cardiovascular deaths (12%), liver disease (6%), and malignancy (4%).
      CONCLUSION: Graft survival rates were comparable with previous reports. However,
      the proportion of death with functioning graft and cardiovascular death as a
      cause of graft and patient loss is lower than that of Caucasian populations.

PMID- 21168615
TI  - Risk factors and outcome of delayed graft function after cadaveric kidney
      transplantation: a report from the Thai Transplant Registry.
AB  - INTRODUCTION: Kidney transplantation is the best treatment for end-stage renal
      disease patients. Delayed graft function (DGF) remains one of the major problems
      after cadaveric kidney transplantation. This study has reported the risk factors
      and outcomes of DGF using data from Thai Transplant Registry Database. METHODS:
      The data of all cadaveric kidney transplantations (CD-KT) were retrieved from the
      database. DGF was defined as a failure to decrease the serum creatinine within 72
      hours or a requirement for dialysis within the first week after transplantation.
      We performed logistic regression analysis to correlate donor features (age, sex,
      cardio-pulmonary resuscitation (CPR), brain death from a cerebrovascular accident
      (CVA), best and last serum creatinine) with recipient demographics (age, sex) and
      clinical outcomes cold ischemic time [CIT] and DGF. RESULTS: We analyzed 756 CD
      KT including 320 (42%) patients experiencing DGF. Upon multivariate analysis,
      factors significantly correlated with DGF were CIT (P < .001), donor last serum
      creatinine (P < .001), interleukin 2 monoclonal antibody induction (P = .004),
      donor age (P = .017), donor CVA (P = .012), and prior peritoneal dialysis (PD) (P
      = .012). There was no significant correlation between DGF and donor height,
      weight, sex, CPR, brain death from CVA, best serum creatinine, recipient age, or
      sex in multivariate analysis. Graft survivals at 1 and 5 years after
      transplantation were significantly lower among the DGF group namely, 91.0% vs.
      95.2% and 78.7% vs. 86.0%, respectively (P = .006). Patient survival was also
      significantly lower 94.1% vs. 96.4% and 82.1% vs. 92.2%, respectively, (P =
      .001). CONCLUSION: A higher value of the donor's terminal serum creatinine, CIT,
      IL2mAb induction, PD prior to KT and donor age increased the risk for DGF after
      CD-KT. DGF significantly lowered kidney allograft and patient survivals at 1 and
      5 years after transplantation among the Thai population.

PMID- 21168616
TI  - C4d binding correlated with strong HLA antibodies involved in graft failures.
AB  - Capillary C4d was an established marker of antibody-mediated rejection in kidney
      transplantation. Recently, C4d fixation to antibodies against HLA-coated beads
      were found to be a novel way to test for complement-fixing antibodies in the
      serum. To find differences between complement-fixing and nonfixing antibody
      assays, we tested HLA antibodies and C4d in 102 sera of graft-failure patients
      using the LABScreen and FlowPRA bead methods. HLA antibodies were observed in the
      sera of patients who subsequently failed and who continued to function. C4d
      fixing antibodies were present in the sera of patients who subsequently
      experienced graft failures and those with high fluorescence intensity of HLA
      antibodies by FlowPRA. In antibody dilution studies with LABScreen, we noted that
      C4d fixation occurred only at high antibody titers, and fluorescence was lost as
      sera were diluted. In conclusion, the fluorescence levels of antibodies were more
      important that the C4d content. Quantitative aspects of antibody testing using
      the fluorescence value appears to be a valuable factor when examining anti-HLA
      antibodies posttransplantation.

PMID- 21168617
TI  - Early kidney graft size and Doppler parameters are associated with kidney graft
      function 1 year after transplantation.
AB  - BACKGROUND: The aim of this study was to assess the association of various
      ultrasonography (US) and Doppler parameters of kidney graft as measured at 1
      month posttransplant with 1-year graft function. MATERIALS AND METHODS: The study
      cohort included 125 adult recipients of deceased donor kidney transplantations
      between January 2006 and February 2009. All patients underwent an US-Doppler
      examination performed by a trained nephrologist at 1 month posttransplant using
      an Acuson-Siemens Sequoia 512. Graft length and intrarenal Doppler indices were
      measured at the midsegmental artery level. Relative graft size was calculated by
      dividing graft length with body mass index. Graft function was assessed at 1 year
      by estimated glomerular filtration rate (eGFR) using the 4-variable Modification
      of Diet in Real Disease study equation. Linear and logistic regression analyses
      were used to assess the relationship between US-Doppler parameters and eGFR.
      RESULTS: Univariate linear regression showed a significant correlation between
      eGFR at 1 year and graft length at 1 month (P = .009), relative graft length
      <0.50 cm per kg/m(2) (P = .004), resistance index >0.75 (P = .031), and end
      diastolic velocity <9 cm/sec (P = .006). Logistic regression analyses showed that
      eGFR <60 mL/min/1.73 m(2) at 1 year was significantly associated with graft
      length <12 cm at 1 month (odds ratio [OR], 2.4; 95% confidence interval [CI],
      1.16-4.92; P = .017), relative graft length <0.5 cm per kg/m(2) (OR, 2.54; 95%
      CI, 1.20-5.35; P = .014), resistance index >0.75 (OR, 2.86; 95% CI, 1.30-6.29; P
      = .009), and end-diastolic velocity <9 cm/sec (OR, 2.37; 95% CI, 1.01-5.56; P =
      .047). CONCLUSION: In this retrospective analysis, kidney transplant recipients
      with greater graft length at 1 month, specifically when standardized to body
      size, showed better graft function at 1 year posttransplantation. Higher
      intrarenal diastolic blood flow and lower resistance index at 1 month were also
      predictive of better graft function at 1 year.

PMID- 21168618
TI  - Low-dose steroid maintenance for renal transplant recipients.
AB  - OBJECTIVES: We investigated the efficacy and safety of an immunosuppressive
      regimen consisting of tacrolimus or cyclosporine, with basiliximab, mycophenolate
      mofetil or mizoribine, and low-dose steroids (prednisone <2.5 mg/d) for kidney
      transplant recipients. METHODS: We conducted a prospective study of 51 recipients
      with stable graft function who underwent kidney transplantation between August
      2005 and December 2009. The oral dose of prednisone was gradually tapered to <2.5
      mg/d within 2 months after transplantation. We assessed, patient and graft
      survivals, incidence of rejection episodes, transplant function and steroid side
      effects. RESULTS: Death-censored graft survival was 100%, and the mean serum
      creatinine levels remained stable at 1.31, 1.37, and 1.48 mg/dL at 1, 2, and 3
      years, respectively, after transplantation. There were seven biopsy-proven
      rejection episodes (mean = 110 days; range = 14-436) after prednisone was
      decreased. The cumulative incidence of biopsy-proven rejection was 11.2%, 17.0%,
      and 17.0%, respectively. In addition, the mean blood pressure was stable (127/78
      mm Hg, 125/77 mm Hg, and 125/76 mmHg, respectively), whereas the mean serum
      cholesterol and triglyceride levels remained within normal limits. Only 3
      patients (7%) displayed new onset diabetes after transplantation. CONCLUSION: Low
      dose steroid maintenance therapy is safe with beneficial effects on
      cardiovascular risk factors.

PMID- 21168619
TI  - Cyclosporine and mycophenolate mofetil 48 hours before renal transplantation
      enables the use of low cyclosporine doses and achieves better graft function.
AB  - Reducing calcineurin-inhibitor induced nephrotoxicity and simultaneously avoiding
      long-term side effects are desirable goals in renal transplantation. We examined
      the hypothesis that administration of cyclosporine and mycophenolate mofetil
      (MMF) 48 hours before renal transplantation allows reduction in the target
      cyclosporine C2 concentration, thus decreasing toxicity and improving graft
      function. We enrolled 80 kidney recipients in a single-center study comparing 2
      cyclosporine-based protocols. Group I patients (n = 40) received a standard dose
      of cyclosporine (blood cyclosporine C2, 800-1500 ng/mL) with MMF and standard
      doses of corticosteroids. Group II patients (n = 40) were treated with a low dose
      of cyclosporine (blood cyclosporine C2, 450-800 ng/mL) and MMF plus low doses of
      corticosteroids after induction 48 hours before surgery with cyclosporine and
      MMF. Patient (97.5% vs 100%) and graft survivals (92.5% vs 95%) at 1 year were
      not different between the groups, although patients in group II experienced
      significantly fewer acute rejection episodes (10% vs 30%; P < .01). Delayed graft
      function occurred less often among group I than group II (17.5 vs 20%), but the
      difference was not significant. Graft function at 1 year was significantly better
      among group II (serum creatinine 1.31 vs 1.64 mg/dL and creatinine clearance 63
      mL/min versus 47 mL/min; P < .05). We concluded that administration of
      cyclosporine and MMF 48 hours before renal transplantation allowed the safe
      effective use of low target C2 cyclosporine concentrations, enabling an early
      decrease in cyclosporine dose. These preliminary results indicated better 1-year
      graft function compared with the normal cyclosporine dose regimen.

PMID- 21168620
TI  - The effect of later change or modulation of immunosuppression on long-term renal
      transplant results.
AB  - Proper maintenance of immunosuppression is required to achieve long-term graft
      survival. The aim of this study was to evaluate the effect of change or
      modulation of an immunosuppressive regimen (IR) on graft survival during the
      posttransplant period in patients undergoing kidney transplantation. A total of
      1164 patients who underwent kidney transplantation between January 1997 and
      December 2008 at Yonsei University Health System were enrolled. All patients
      initially received calcineurin inhibitor (CNI)-based double or triple IR (DIR and
      TIR, respectively). The causes of IR changes or modulation were reviewed
      retrospectively. Graft survival rate was compared according to types of
      maintenance immunosuppression (DIR versus TIR). Initially, DIR and TIR were
      adopted in 201 (17.3%) and 963 (82.7%) recipients, respectively. In 77 DIR
      recipients (38.8%) and 271 TIR recipients (28.1%), IRs were changed. Among
      recipients of an initial DIR, the most frequent reasons for IR change were acute
      rejection (50%) within 6 months of transplantation and chronic allograft
      dysfunction (70%) after 6 months. In TIR recipients, the reasons for IR change
      included drug toxicity or drug-related side effects (34.3%) within 6 months of
      transplantation and complications related to overimmunosuppression (39.3%) after
      6 months. The group in which the IR was changed from the initial DIR to the later
      TIR had a statistically superior graft survival rate compared to the group that
      did not have a change in the initial DIR (P = .032). In contrast, TIR recipients
      without change had better graft survival rate than recipients with initial TIR
      change to later DIR (P < .001). Change or modulation of immunosuppression from
      initial DIR to later TIR could affect long-term graft survival.

PMID- 21168621
TI  - Long-term outcome of very early cyclosporine minimization and de novo everolimus
      therapy in kidney transplant recipients: a pharmacokinetic guided approach.
AB  - BACKGROUND: Cyclosporine (CsA) nephrotoxicity is an important cause of chronic
      allograft dysfunction. Clinical information concerning the impact of very early
      CsA dose reduction in kidney transplant recipients is limited. We have examined
      the long-term outcomes of very early CsA dose reduction. This is synchronized
      with de novo everolimus and steroid therapy. METHODS: We enrolled 10 de novo
      kidney transplant recipients to receive CsA (target C(0) 250-350 ng/mL) and
      prednisolone as initial therapy. CsA dosage was reduced by 50% at posttransplant
      day 7. Everolimus (target trough level, 3-8 ng/mL) was concomitantly started at
      the day of CsA reduction. Full pharmacokinetic studies of everolimus and CsA were
      studied at the period of 4-8 weeks after CsA reduction. CsA was then gradually
      reduced to maintain a trough level of 50-100 ng/mL and/or C(max) <600 ng/mL.
      RESULTS: The mean follow-up was 51.2 +/- 3.45 months. The nadir serum creatinine
      was 1.03 +/- 0.33 mg/dL. The mean initial estimated glomerular filtration rate
      (eGFR) was 97.97 +/- 23.36 mL/min. The mean initial trough everolimus was 5.2 +/-
      1.5 ng/mL. The eGFR at 1 year, 3 years, and last follow-up was 82 +/- 25, 80 +/-
      21, and 80 +/- 25 mL/min, respectively. Patient and graft survival was 100%.
      CONCLUSION: Very early CsA dose reduction synchronized with de novo everolimus
      therapy was associated with good long-term patient and graft survival in kidney
      transplant recipients. This intervention can lead to 75% CsA minimization and is
      associated with very good GFR by the modification of Diet in Renal Disease
      Formula at year 4.

PMID- 21168622
TI  - Pretransplant soluble CD30 serum concentration does not affect kidney graft
      outcomes 3 years after transplantation.
AB  - INTRODUCTION: An elevated serum concentration of soluble the form of CD30
      (sCD30), an activation marker of mainly T(H)2-type cytokines producing T
      lymphocytes, has been reported as a predictive factor for acute cellular
      rejection episodes and poor graft outcomes in kidney transplantation. This
      historic cohort study investigated the association of a pretransplant sCD30 serum
      concentrations with kidney graft function and graft survival 3 years
      posttransplantation in adult recipients of deceased donor kidney grafts, treated
      with monoclonal anti-CD25 antibodies as an induction treatment combined with a
      cyclosporine (CsA)-based maintenance triple therapy. MATERIALS AND METHODS: The
      pretransplant sera of 296 recipients were tested for sCD30 content using a
      microsphere flow-cytometry assay. The estimated glomerular filtration rate (eGFR)
      was determined by the 4-variable Modification of Diet in Renal Disease equation.
      The incidences of graft loss were calculated with the use of Kaplan-Meier
      survival analysis and compared using the log-rank test. RESULTS: According to the
      distribution of the pretransplant sCD30 levels concentration >=2700 pg/mL was
      defined as high (n = 146) and concentration <2700 pg/mL as low (n = 150). Three
      years posttransplantation, the eGFR was not significantly different in the
      recipients in high and low sCD30 groups (65 +/- 24 vs 67 +/- 21 mL/min/1.73 m(2);
      P = .43); there was no association between the eGFR 3 years after transplantation
      and the pretransplant sCD30 levels (r(2) = 0.002; P = .49). Graft survival 3
      years after transplantation was also not different in the recipients in high and
      low sCD30 groups (P = .52). CONCLUSION: In our adult deceased-donor kidney graft
      recipients, the pretransplant sCD30 serum concentration was not a predictive
      factor of immunologic risk associated with the kidney graft function 3 years
      posttransplantation; neither did it affect graft survival 3 years after
      transplantation. The immunosuppression with anti-CD25 antibodies as an induction
      treatment combined with the CsA-based maintenance triple therapy could possibly
      be decisive for our findings.

PMID- 21168623
TI  - Improvement of graft function after conversion to once daily tacrolimus of stable
      kidney transplant patients.
AB  - BACKGROUND: Chronic renal dysfunction is present in about one quarter of kidney
      transplant patients at 1 year and in about 90% by 10 years. Nephrotoxicity caused
      by calcineurin inhibitors is among the most common factors. Elevated tacrolimus
      levels have been correlated with worse control of side effects including acute
      and/or chronic nephrotoxicity. The aim of this study was to observe the effects
      on graft function of conversion from the twice daily to the once daily extended
      release tacrolimus formulation in stable kidney transplant recipients within 5
      years of grafting. METHODS: Thirty-one stable kidney transplant patients were
      converted at the same dosage (1 mg:1 mg). Patients served as their own controls
      based on results before versus after conversion. RESULTS: The trough levels of
      tacrolimus showed a slight albeit significant reduction after the conversion.
      Serum creatinine and glomerular filtration rate showed a significant improvement
      without an association with the tacrolimus trough levels. CONCLUSION: We suggest
      that the immunosuppression with once daily tacrolimus may be a good option for
      kidney transplant patients.

PMID- 21168625
TI  - The long-term outcomes of transplantation of kidneys with multiple renal
      arteries.
AB  - Kidneys with multiple renal arteries are increasingly procured for
      transplantation. To compare the outcomes of kidney transplantation using
      allografts with multiple arteries, we studied long-term graft function and
      survival according to their number of arterial anastomoses during an 18-year
      period from July 1, 1990, through December 31, 2008, in which only the
      recipient's external iliac artery or internal iliac artery was used for
      anastomosis (n = 1186). The recipients were divided into four groups: group I,
      single renal artery with single anastomosis (n = 890, 75.0%); group Il, multiple
      renal arteries, single anastomosis (n = 26, 2.2%); group Ill, multiple renal
      arteries, multiple anastomoses (n = 236, 19.9%); and group IV, polar artery
      ligation (n = 34, 2.9%). We compared the following variables patient and graft
      survivals; mean creatinine levels at 1 and 6 months, as well as 1-, 3-, and 5
      years posttransplant; the number of acute rejection episodes, and the rates of
      vascular and urologic complications. The creatinine values and incidences of
      acute rejection episodes did not differ significantly (P = 0.399 and P = 0.990,
      respectively). There were no significant differences among the four groups in
      graft survival (P = 0.951), patient survival (P = 0.751), incidence of vascular
      (P = 0.999) or urologic complications (P = 0.371). The four groups were
      subdivided according to the recipient arterial anastomosis to the main graft
      renal artery. The subdivided groups showed no significant differences in graft or
      patient survival, or complications rates. The results indicated that multiplicity
      of renal arteries in kidney transplantation did not adversely affect allograft or
      patient survival compared with single renal artery transplantation. Moreover, the
      type of the arterial anastomosis (main renal artery end-to-end anastomosed to
      internal iliac artery or end-to-side anastomosed to external iliac artery
      appeared to not affect graft or patient survival or the incidence of vascular or
      urologic complications.

PMID- 21168624
TI  - Neither mycophenolate acyl-glucuronide levels nor their areas under the curve are
      responsible for the gastrointestinal side effects in kidney transplant recipients
      receiving EC-MPA: a prospective trial.
AB  - INTRODUCTION: Since previous in vitro studies suspected the metabolite
      mycophenolate acyl-glucuronide (AcMPAG) to be responsible for the
      gastrointestinal side effects, we examined the correlation between AcMPAG blood
      levels and patient gastrointestinal satisfaction inquiries using a standardized,
      validated questionnaire. PATIENTS AND METHODS: We enrolled 63 renal transplant
      patients, however, two discontinued the study and 16 were excluded because of
      inadequate completion of the questionnaires or missing blood values or
      discontinuation of enteric coated mycophenolic acid (EC-MPA) therapy, severe side
      effects or viral infections. The final responses of 45 people were subjects to
      statistical analysis. Gastrointestinal side effects were examined using the
      Gastrointestinal Symptom Rating Scale (GSRS) completed at three times: T1 (3-5
      days after transplantation), T2 (10-15 days), and T3 (3 months). The GSRS results
      generated two groups of patients based on cutoff values set at a score of 4
      points for each item. Scores less than 4 were assumed to be "no side effects";
      >=4, "side effects." AcMPAG was measured by mass spectroscopy on blood samples
      obtained at fixed times generating three pharmacokinetic profiles per patient.
      RESULTS: There was no relation between high AcMPAG blood concentrations and
      gastrointestinal dissatisfaction. Neither Ac-MPAG area under the curve (AUC) in
      the absorption phase nor AcMPAG peak values correlated with gastrointestinal
      dissatisfaction. CONCLUSION: There was no significant correlation between mean
      AcMPAG and GSRS scores, although previous studies had suggested AcMPAG maximum
      values or alternatively AcMPAG AUC in the absorption phase to relate to side
      effects.

PMID- 21168626
TI  - One-year follow-up of kidney transplant recipients with increased expression of
      mRNA for granzyme B in urinary cells.
AB  - BACKGROUND: Measurement of mRNA encoding cytotoxic proteins in urinary cells is
      recognized as a potential noninvasive means to diagnose acute rejection in kidney
      allograft recipients. We sought to evaluate kidney graft function after 1 year
      follow-up without therapeutic intervention among patients with increased urinary
      expression of mRNA for granzyme B, albeit with stable graft function at the time
      of measurements. PATIENTS AND METHODS: The 29 randomly selected patients were at
      a median of 39 months (range, 10-156) after transplantation with stable graft
      function over the previous 3 months. The reference housekeeping gene GAPDH was
      used for expression measurement in a TaqMan Gene Expression Assay with the target
      granzyme B gene. Delta delta ct relative gene expression analysis compared
      results with reference samples from 10 healthy individuals. Kidney graft function
      was reassessed after 1 year follow-up; immunosuppression was not changed during
      this period. RESULTS: mRNA granzyme B expression was significantly higher among
      the group of randomly assessed out-clinic patients with stable graft function
      than among healthy volunteers (mean +/- standard error of the mean, 6.18 +/-
      1.27; P < .01). Despite no therapeutic intervention, no significant changes were
      observed in delta glomerular filtration rate or quantitative proteinuria between
      groups with mRNA expression > 5* versus <2* higher than the healthy controls at 1
      year of follow-up. CONCLUSION: Increased mRNA expression for granzyme B in
      urinary cells over the medium to long term among kidney transplant recipients did
      not predict changes in renal allograft function after 1 year follow-up.

PMID- 21168627
TI  - Evaluation of arterial stiffness after successful renal transplantation using
      brachial-ankle pulse wave velocity.
AB  - BACKGROUND: Cardiovascular disease remains a main cause of mortality in renal
      transplant recipients. Determination of aortic stiffness with pulse wave velocity
      (PWV) is considered a strong predictor of cardiovascular risk. We investigated
      arterial stiffness with brachial-ankle pulse wave velocity (baPWV) after
      successful renal transplantation. METHODS: We studied 197 patients (mean age =
      53.2 +/- 10.8 years) who underwent successful renal transplantation. baPWV was
      evaluated with a noninvasive automatic Omron Colin device. During follow-up (mean
      = 183.8 +/- 108.9 months), we investigated parameters of sex, age, body mass
      index, duration before (dialysis) and after transplantation, and cardiovascular
      risk factors (hypertension and diabetes). In all subjects, fasting concentrations
      of serum creatinine, non-(HDL) high-density lipoprotein-cholesterol (total
      cholesterol minus HDL-cholesterol), low-density lipoprotein-cholesterol, and
      triglyceride were also compared with those at enrollment. RESULTS: Mean baPWV
      levels were 1519 +/- 329 cm/s in our renal transplant recipients. baPWV increased
      independent of age, duration of dialysis before transplantation, and
      cardiovascular risk factors. Serum creatinine and dilation did not show any
      significant correlations to baPWV. CONCLUSION: In renal transplant recipients,
      baPWV may be more influenced by past clinical history before transplantation than
      by current condition. Noninvasive assessment of arterial stiffness with baPWV may
      be a useful and convenient indicator of cardiovascular disease after renal
      transplantation.

PMID- 21168628
TI  - Subclinical left ventricular echocardiographic abnormalities 1 year after kidney
      transplantation are associated with graft function and future cardiovascular
      events.
AB  - Cardiovascular events (CVE) are the leading cause of mortality in kidney
      transplant recipients. Increased left ventricular mass (LVM) is a risk factor for
      CVE. This study investigated the associations of LVM with impaired kidney graft
      function expressed as lower glomerular filtration rate (GFR) at 1 year after
      transplantation and future CVE beyond 1 year. The prospective study cohort
      included 68 nondiabetic recipients of a kidney transplant between January 2004
      and December 2005 who underwent a transthoracic echocardiographic investigation
      at 1 year after transplantation. LVM and left ventricular hypertrophy (LVH) were
      assessed using 2-dimensional M-mode echocardiography. GFR was estimated (eGFR) by
      the 4-variable Modification of Diet in Renal Disease formula. Cox proportional
      hazards analysis was used to estimate cardiac CVE (angina pectoris, acute
      myocardial infarct, coronary angioplasty or bypass surgery, or sudden cardiac
      death) hazard ratios (HRs) for patients with LVH versus control subjects with no
      LVH at 1 year after transplantation. All patients had normal systolic function
      (ejection fraction >50%) with no symptoms or signs of heart failure. LVH was
      present in 44 patients (65%). LVM and incidence of LVH were increased in 28
      patients with eGFR <60 mL/min/1.73 m(2) compared with 40 patients with eGFR >=60
      mL/min/1.73 m(2) (248 +/- 61 g and 86% vs 210 +/- 46 g and 50%, respectively; P <
      .01). After a median follow-up of 4.5 years, there were 18 (26.5%) cardiac CVE.
      The incidence of CVE was higher in patients with LVH than in patients with no LVH
      at 1 year after transplantation (36.4% vs 8.3%; P = .020). In adjusted analyses,
      LVH was associated with an increased risk for future CVE (HR, 4.69; 95%
      confidence interval, 1.02-21.5; P = .037). In kidney transplant recipients, a
      lower eGFR at 1 year after transplantation was associated with greater LVM and
      higher incidence of LVH. Presence of LVH was associated with an increased risk
      for future CVE.

PMID- 21168629
TI  - Posttransplant diabetes mellitus: analysis of risk factors, effects on
      biochemical parameters and graft function 5 years after renal transplantation.
AB  - OBJECTIVE: To know the risk factors for posttransplant diabetes mellitus (PTDM)
      and its effects on biochemical parameters and graft function at the end of 5
      years. MATERIALS AND METHODS: We retrospectively analyzed the 218 records of
      postrenal transplant patients who had a minimum follow-up for 5 years. Patients
      were divided into those with diabetes mellitus (DM; n = 21), PTDM (n = 58) and
      non-DM-non-PTDM (n = 139). RESULTS: 29.4% of non-diabetics developed diabetes
      mellitus after transplantation in 5 years, with cumulative rates of 14.01% and
      19.8% at 3 and 12 months, respectively. The incremental incidence was 14.97%
      during the first posttransplant year. The earliest presentation of PTDM was 9
      days after transplant, and 53.45% of patients were asymptomatic at presentation.
      The following were risk factors: recipient age >36 years, hepatitis C virus
      infection, HLA-B13, family history of DM, body mass index >30, and calcineurin
      inhibitor therapy. These features were not risk factors: donor age, donor sex,
      recipient sex, cadaver donor, and antirejection therapy. The PTDM group members
      received the same number of antihypertensive drugs and statin doses and displayed
      similar levels of proteinuria. PTDM had no influence on biochemical parameters.
      The PTDM group had reduced graft function compared with non-DM-non-PTDM subjects,
      when used glomerular filtration rate (estimated by renogram and calculated by
      MDRD formula) as marker, but not creatinine. The rate of urinary tract infections
      was higher among the PTDM group. CONCLUSION: Regular screening of plasma glucose
      is recommended from the early transplant period, particularly among high-risk
      patients. Regular monitoring of graft function using the MDRD formula or isotope
      renogram is necessary as PTDM influences graft function.

PMID- 21168630
TI  - Risk factors for the development of new-onset diabetes mellitus in a living
      related renal transplant program.
AB  - New-onset diabetes mellitus is associated with considerable morbidity after
      transplantation. We evaluated 78 living related renal transplant recipients due
      to all causes except diabetic nephropathy a waiting a living related renal
      transplantation. We evaluated demographic characteristics, pretransplant glycemic
      profile, fasting C-peptide levels, plasma insulin levels, pretransplant insulin
      resistance, and immunosuppression protocols. Among the 16.7% of patients
      developing diabetes mellitus at the end of 1 year, age, family history, and
      impaired glucose tolerance at the time of transplantation correlated with the
      development of diabetes mellitus in the posttransplant period.

PMID- 21168631
TI  - The effect of hyperuricemia on endothelial biomarkers and renal function in
      kidney allograft recipients.
AB  - BACKGROUND: Uric acid may play a pathogenic role in hypertension, cardiovascular
      morbidity, and kidney disease. The aim of this study was to assess the effect of
      serum uric acid on biomarkers of endothelial activation and renal function in
      kidney allograft recipients during 30 months of follow-up. METHODS: The study
      included 100 allograft recipients with stable renal function (estimated
      glomerular filtration rate (eGFR) >60 mL/min). The study was performed 34 +/- 12
      months after transplantation. The patients were followed prospectively for 30
      months. Seventy patients displayed hyperuricemia (uric acid 7.5 +/- 1.0 mg/dL)
      and 30 normouricemia (5.5 +/- 0.9 mg/dL). Concentrations of plasma resistin,
      soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble CD146, and high
      sensitivity C-reactive protein (hs-CRP) were assessed in patients at the
      beginning and after 30 months of follow-up. Clinical outcomes and biomarker
      values were analyzed in these groups and compared to a control group of 26
      healthy volunteers. RESULTS: Concentrations of resistin and CD146 were increased
      among the hyperuricemia versus the normouricemic group (P < .05). Serum uric acid
      level correlated with sVCAM-1, hs-CRP, resistin, and sCD146 concentration in both
      groups of kidney recipients (P < .01). Serum creatinine concentrations correlated
      with sVCAM-1, resistin, and sCD146 concentrations (P < .01). There were
      significant direct correlations between uric acid and the number of
      antihypertensive agents (P < .001) and inverse correlations between eGFR (P <
      .001) and high-density lipoprotein cholesterol (P < .04). Pulse pressure
      increased in hyperuricemic patients during follow-up (P < .05). The decrease in
      eGFR during the 30-month follow-up was similar in both groups. No subject
      progressed to kidney allograft failure. Patient and graft survivals were 98%
      among hyperuricemic and 96.7% among normouricemic individuals. CONCLUSIONS:
      Hyperuricemia may injure endothelial function via resistin-dependent mechanisms.
      It represents a risk factor for arterial stiffness. The elevated serum uric acid
      may not have a causal role in the progression of renal transplant injury over 30
      months of follow-up.

PMID- 21168632
TI  - Treatment of hyperparathyroidism with cinacalcet in kidney transplant recipients.
AB  - BACKGROUND: After successful kidney transplantation, hyperparathyroidism can
      persist in 10%-50% of patients and can harmfully affect bone metabolism.
      Calcimimetic cinacalcet is a new treatment option in the management of persistent
      hyperparathyroidism in these patients. METHODS: This prospective, clinical study
      of 11 patients included those who had a serum intact parathyroid hormone (iPTH)
      concentration >65 ng/L, a serum creatinine concentration was <200 MUmol/L, stable
      kidney graft function, and were >1 year since transplantation. Patients were not
      treated with drugs other than calcitriol that could influence bone metabolism.
      During the 6-month observation period, in which the stability of measured
      parameters was determined, and in the 12-month treatment period (cinacalcet 30
      mg/d), we followed serum concentrations of calcium, phosphate, iPTH, creatinine,
      vitamin 25OH D(3), bone-specific alkaline phosphatase (ALP), osteocalcin,
      collagen degradation fragments (CTX), urinary calcium excretion, and bone mineral
      density (BMD). RESULTS: During the treatment period, the serum calcium
      concentration decreased significantly (from 2.50 +/- 0.12 to 2.32 +/- 0.12
      mmol/L; P < .01). Serum iPTH concentration decreased significantly (from 247
      [range, 199-362] at time 0 to 198 [range, 165-233] ng/L after 1 month of
      treatment; P < .05), but increased slightly thereafter. After 6 months of
      treatment, the serum concentration of ALP and CTX increased significantly, but
      decreased thereafter. There were no significant changes in the other parameters
      assessed. Renal function remained stable during the treatment period. The BMD of
      the lumbar spine, hip, and forearm did not change during the 12 months of
      treatment. CONCLUSION: Cinacalcet was effective in treating posttransplant
      hyperparathyroidism, resulting in decreased calcemia and transient decreased
      iPTH. ALP and CTX transiently increased during therapy, but other markers of bone
      metabolism remained unchanged. Twelve months of cinacalcet treatment did not
      result in a change in BMD. Cinacalcet seems to be a safe drug with no negative
      effect on renal function.

PMID- 21168633
TI  - Evaluation of a preemptive strategy for BK polyomavirus-associated nephropathy
      based on prospective monitoring of BK viremia: a kidney transplantation center
      experience.
AB  - INTRODUCTION: BK polyomavirus-associated nephropathy (BKPVAN) is a major cause of
      renal failure early after kidney transplantation. The present study reports the
      preliminary results of prospective monitoring including a preemptive strategy for
      BKPVAN during the first year after kidney transplantation. METHODS: We monitored
      BK virus DNA in blood at months 1, 2, 3, 6, 9, and 12 among 92 subjects who
      received induction therapy (basiliximab or antithymocyte globulin), and
      maintenance immunosuppression with prednisone, mycophenolate mofetil, and
      tacrolimus. Patients with two or more consecutive measurements of viral load
      >10(4) copies/mL were treated with a stepwise approach including dose reduction
      or discontinuation of mycophenolate mofetil eventually followed by reduction of
      tacrolimus and introduction of leflunomide. RESULTS: Within 1 year, seven (7%)
      patients displayed sustained BK viremia at a median of 92 days after
      transplantation. Among 68 patients who underwent a renal allograft biopsy, seven
      were diagnosed as BKPVAN at a median of 15 weeks after transplantation. The
      diagnosis was achieved by a surveillance biopsy in four patients with stable
      renal function. BKPVAN was preceded by asymptomatic viremia except for two cases
      in whom BK viremia occurred at 6 or 11 months, after the histological diagnosis.
      At 12 months, six patients had cleared their viremia. Serum creatinine levels had
      stabilized in six recipients with BKPVAN estimated renal function was 43.7 +/-
      16.3 mL/min in patients with viremia and/or BKPVAN versus 61.3 +/- 20.1 mL/min
      among patients who never became viremic (P = .03). None of the patients with
      viremia and/or BKPVAN lost the allograft. CONCLUSION: BKPVAN may occur early
      after kidney transplantation, at a low or undetectable viremia or at some weeks
      after the first positive viremia. Intensive monitoring during the first 4 months
      after transplantation together with early protocol biopsies or interventions
      prompted by BK viremia may optimize BKPVAN diagnosis at a subclinical stage, thus
      avoiding renal dysfunction.

PMID- 21168634
TI  - Routine BK virus surveillance in renal transplantation--a single center's
      experience.
AB  - BACKGROUND: We started a universal screening of all our kidney transplant
      recipients for BK virus in 2005. This review of our experience includes patients
      with >=6 months' posttransplantation follow-up. METHODS: We performed a
      retrospective chart evaluation of all kidney transplants from January 2005 to
      February 2010. Urine polymerase chain reaction (PCR) for BK virus was done on all
      patients starting from 4 weeks after transplantation. If negative, it was
      repeated monthly for the first 6 months and then every 3-4 months. If the test
      was positive, a urine and blood BK virus PCR done on the next visit was repeated
      every 2-4 weeks with a slow reduction in immunosuppression. RESULTS: From January
      2005 to February 2010 we performed 173 kidney transplantations with 12 graft
      losses within the first 6 weeks which were excluded from the analysis. Induction
      immunosuppression consisted of anti-interleukin-2 receptor antibody (n = 102) or
      antithymoglobulin (ATG; n = 59). In 112 patients (70%), the urine BK virus PCR
      remained negative; 18 (11%) only the urine was positive and among an additional
      31 (19%) BK virus PCR was positive in blood. There was no difference in incidence
      according to induction therapy. Delayed graft function was observed among 39
      patients (24%); there was no difference in the incidence of BK virus with versus
      without DGF. The mean time to first detection was shorter with ATG induction
      (mean, 199 days; median, 90 days; range, 26-1198 days) compared with anti-IL-2
      (mean, 321 days; median, 195 days; range, 23-1077 days). Urine-only positivity
      was first detected from 37 to 1198 days (mean, 366 days; median, 227 days) and
      blood positivity from 23 to 1069 days (mean, 216 days; median, 90 days). Among BK
      positive patients, 26 (53%) were detected within the first 6 months and 38 (76%)
      within the first year. With reduction in immunosuppression, there was gradual
      reduction or elimination of positive PCR tests in all cases except one, which
      resulted in graft failure. CONCLUSIONS: Routine BK virus surveillance is
      effective; it tends to detect BK virus replication early, allowing reduction of
      immunosuppression, which results in good outcomes with renal preservation.

PMID- 21168635
TI  - Adenovirus infection after kidney transplantation in Thailand: seasonal
      distribution and potential route of acquisition.
AB  - BACKGROUND: Data on the epidemiology and route of acquisition of adenovirus (ADV)
      infection after kidney transplantation are limited. From April 2007 to March
      2010, there were 17 cases of ADV infection: namely, 2 from April to December
      2007; 8 from January to December 2008; 4 from January to December 2009; and 3
      from January to March 2010. Most cases occurred in October and November (n = 8;
      47.1%), followed by February to April (n = 6; 35.3%) and July (n = 3; 17.6%).
      METHODS: From April 2007 to August 2009, the diagnosis of ADV infection was made
      based on patient symptoms. From September 2009 to March 2010, in addition to
      symptoms, the diagnosis was complemented by urine surveillance for ADV using real
      time polymerase chain reaction (PCR) prospectively performed every 1-2 weeks
      among recipients of living-related kidney, starting at week 2 posttransplantation
      for a total of 8-12 weeks. Before transplantation, recipients and donors were
      screened for ADV in urine and also using nasal swab. RESULTS: Only 1 of the 24
      patients displayed a positive ADV PCR in the urine surveillance study. A local
      investigation during a cluster of cases in October 2008 showed 2 patients who
      developed ADV after sharing a room in the transplant unit. Although nosocomial
      transmission was probable, the majority of cases were scattered over time rather
      than clustering in 1 time period. CONCLUSION: These findings suggested that ADV
      infection cases occurred after exogenous exposure. In a resource-limited country,
      early diagnosis of ADV is justified for patients with compatible symptoms
      complemented by intense infection control to prevent nosocomial transmission from
      a confirmed case.

PMID- 21168636
TI  - Incidence and risk factors for pulmonary mycosis in kidney transplantation.
AB  - INTRODUCTION: Pulmonary mycosis, a severe complication following kidney
      transplantation, is associated with a high rate of mortality. The incidence of
      and independent risk factors for its development have not been well studied.
      METHODS: We retrospectively reviewed 2573 kidney transplant recipients. Patients
      were divided into case and control groups based on a diagnosis of pulmonary
      mycosis. The recipient baseline characteristics, posttransplant complications,
      immunosuppressive regimens and antibiotic usages were analyzed to identify
      independent risk factors. RESULTS: The total incidence of pulmonary mycosis among
      kidney recipients was 2.1%. Upon univariate analysis, patients in the case group
      differed significantly from the controls based upon: older age, higher
      retransplantation rate, longer dialysis time, induction with ATG or anti-CD25
      monoclonal antibodies, maintenance treatment with FK506 or MMF, broad-spectrum
      antibiotics, higher incidences of acute rejection episodes, DGF, impaired liver
      function, leukopenia, cytomegalovirus infection, and delayed incisional healing
      (P < .05). Multivariate analysis showed that older age, retransplantation, ATG
      induction, FK506/MMF, broad-spectrum antibiotics, leukopenia, and delayed
      incisional healing were independent risk factors for pulmonary mycosis.
      CONCLUSIONS: The use of more potent immunosuppressive regimens seems to increase
      the rate of pulmonary mycosis. Patients who have five or more independent risk
      factors are at high risk for developing pulmonary mycosis.

PMID- 21168638
TI  - Japanese-style intensive medical care improves prognosis for acute liver failure
      and the perioperative management of liver transplantation.
AB  - The Japanese style of intensive medical care for acute liver failure has yielded
      high survival rates. The care system comprises artificial liver support (ALS)
      together with treatment for the underlying disease. Plasma exchange in
      combination with high-volume hemodiafiltration using an high performance membrane
      has become the standard ALS system. It is safe, efficiently removing more low and
      middle molecular weight toxic substances than other methods because of the large
      volumes of buffer (more than 200 L per session), resulting in recovery from coma
      in patients with severe fulminant hepatitis, a status comparable with the
      ahepatic state. This ALS is therefore an effective tool to sustain patients with
      fulminant hepatitis in a favorable condition until liver function recovers or
      liver transplantation becomes available. The accompanying treatment for
      underlying disease serves to limit the liver destruction that hampers
      regeneration. The treatment has remarkably improved the prognosis for patients
      with subacute types of fulminant hepatitis, which generally carry a less
      favorable prognosis than the acute type. This treatment system thus provides more
      time for physicians to assess the indications for liver transplantation as well
      as giving the patient a greater chance of undergoing transplantation.

PMID- 21168637
TI  - Liver transplantation in a randomized controlled trial of emergency treatment of
      acutely bleeding esophageal varices in cirrhosis.
AB  - BACKGROUND: Bleeding esophageal varices (BEV) in cirrhosis has been considered an
      indication for liver transplantation (LT). This issue was examined in a
      randomized controlled trial (RCT) of unselected, consecutive patients with
      advanced cirrhosis and BEV that compared endoscopic sclerotherapy (EST; n = 106)
      to emergency direct portacaval shunt (EPCS; n = 105). METHODS: Diagnostic work-up
      and treatment were initiated within 8 hours. Patients were evaluated for LT on
      admission and repeatedly thereafter; 96% underwent over 10 years of regular
      follow-up. The analysis was supplemented by 1300 unrandomized cirrhotic patients
      who previously underwent portacaval shunt (PCS) with 100% follow-up. RESULTS: In
      the RCT long-term bleeding control was 100% following EPCS, only 20% following
      EST. Also, 3-, 5-, 10-, and 15-year survival rates were 75%, 73%, 46%, and 46%,
      respectively, following EPCS compared with 44%, 21%, 9%, and 9% following EST,
      respectively (P < .001). Only 13 RCT patients (6%) were ultimately referred for
      LT mainly because of progressive liver failure; only 7 (3%) were approved for LT
      and only 4 (2%) underwent LT. The 1- and 5-year LT survival rates were 0.68% and
      0, respectively, compared with 81% and 73%, respectively, after EPCS. In the 1300
      unrandomized PCS patients, 50 (3.8%) were referred and 19 (1.5%) underwent LT.
      The 5-year survival rate was 53% compared with 72% for all 1300 patients.
      CONCLUSIONS: If bleeding is permanently controlled, as occurred invariably
      following EPCS, cirrhotic patients with BEV seldom require LT. PCS is effective
      first-line and long-term treatment. Should LT be required in patients with PCS,
      although technically more demanding, numerous studies have shown that PCS does
      not increase mortality or complications. EST is not effective emergency or long
      term therapy.

PMID- 21168639
TI  - Liver recipient survival rate before and after model for end-stage liver disease
      implementation and use of donor risk index.
AB  - BACKGROUND: The progressive increase in the demand for liver transplantation has
      led to changes in donor selection and allocation, such as the Model for End-Stage
      Liver Disease Score (MELD). Characteristics related to the donor, recipient, and
      transplantation procedure influence the results. The use of expanded-criteria
      donors (ECDs) and the donor risk index (DRI) are strategies that have been
      proposed to increase the donors pool. OBJECTIVE: We sought to study liver
      recipient survival before and after MELD implementation as well as the use of
      DRI. METHODS: This retrospective study of prospectively collected data analyzed
      1,786 liver recipients and their donors according to gender, age, cause of brain
      death, intensive care unit time, split liver, infection, ECD, cardiac arrest,
      cold ischemia time, waiting list time, and donor origin. MELD (without special
      scoring) and DRI were calculated from the recorded data. The periods of this
      study were 2004-2006 (pre-MELD) and 2006-2008 (post-MELD). For survival times, we
      performed the Kaplan-Meier method with log-rank tests and Cox regression analysis
      (prediction). The Kolmogorov-Sminorv test was used for sample comparisons.
      RESULTS: The 1-year survivals were similar in the 2 periods (65.4% vs 67.6%). The
      predictive factors for death among the whole population were DRI >1.5, cold
      ischemia time >=9 hours, MELD >=25, female recipient, and longer waiting list
      time. CONCLUSIONS: MELD is an important tool for allocation, resulting in a
      reduced waiting list, increased number of split-liver procedures, and use of ECDs
      without deterioration of survival times. DRI >1.7 was associated with shorter
      survival.

PMID- 21168640
TI  - Large benign hepatocellular nodules in cirrhosis due to chronic venous outflow
      obstruction: diagnostic confusion with hepatocellular carcinoma.
AB  - Budd-Chiari syndrome (BCS) in patients progressing to cirrhosis is an indication
      for liver transplantation. At this stage of disease, it is common to find large
      benign hepatocellular nodules (LBHNs) of undetermined cause that may be confused
      with hepatocellular carcinoma (HCC). Patients with indications for liver
      transplantation are currently classified according to the MELD (Model for End
      Stage Liver Disease) severity score. When they fit Barcelona and Milan
      eligibility criteria for HCC, they receive 20 points. Thus, misdiagnosis of HCC
      leads to a privileged position on the waiting list. Herein, we have reported
      three BCS cases of cirrhotic patients who underwent liver transplantation; the
      pathologic results of their explanted livers showed LBHN. We analyzed three of
      489 OLT who had chronic venous outflow obstruction (CVOO) the first case: was a
      19-year-old man, with BCS of undetermined cause. The second 20-year-old female
      patients displayed BCS due to antiphospholipid syndrome the third, 45-year-old
      man had CVOO diagnosed preliminarily due to cryptogenic cirrhosis in the
      explanted liver. In the three cases, the nodules in the explant measured 0.5 to
      2.4 cm. In the first case, the diagnosis was not in doubt; in the second case, 23
      nodules were confused with HCC histologic evaluation, and in the third case three
      larger hypervascular nodules were misdiagnosed as HCC in the preoperative period
      despite low alpha-fetoprotein levels. In conclusion it is fundamental to
      recognize these benign lesions so as to avoid misdiagnosis, thereby allowing the
      proper selection of candidates for liver transplantation.

PMID- 21168641
TI  - Pretransplant hyponatremia could be associated with a poor prognosis after liver
      transplantation.
AB  - INTRODUCTION: Predicting the prognosis of hepatic cirrhosis is the most accurate
      method to achieve a fair allocation among the liver transplant waiting list
      thereby reducing overall mortality rates. AIM: To study the survival rates of
      recipients who undergo liver transplantation in association with hyponatremia
      rates. METHODS: This retrospective study used a prospectively collected database.
      The characteristics of liver donors and recipients were: age (years), Model for
      End-stage Liver Disease (MELD), MELD Na score, recipient body mass index
      (kg/m(2)), warm ischemia time (minutes), cold ischemia time (minutes), intensive
      care unit time (days), hemocomponents transfused, recipient glycemia (mg/dL) and
      serum sodium (mEq/L), Child-Pugh-Turcotte classification (points), and survival
      time (months). We analyzed all 318 consecutive liver transplantations from
      February 1994 to May 2010 divided into two groups: A (Na > 130 mEq/L) and B (Na
      <= 130 mEq/L). The Kaplan-Meier method was used to evaluate survival rate and the
      Cox regression test to identify predictive factors. RESULTS: Hyponatremic
      patients displayed shorter survival (P = .04). The Cox regression for survival
      time showed that patients with low serum sodium values (group B) had: Child-Pugh
      scores with 1.13% plus risk of death for each point; cold ischemia time with
      1.001% less risk of death for each minute; glycemia with 0.6% for each mg/dL;
      0.66% use of cell-saver; plus a risk of death for each 100 mL plus 1.02% risk of
      death for each year of donor age. CONCLUSION: Hyponatremic cirrhotic patients
      show more advanced stages of disease compared to normonatremic cirrhotics. They
      usually display metabolic or cirrhotic decompensation and comorbidities. When
      these symptoms were associated with the use of extended criteria donors,
      increased cold ischemia time, and intraoperative bleeding, we observed lower
      survival rates.

PMID- 21168642
TI  - Evaluation of blood glucose levels after hepatitis B immune globulin
      administration utilizing two different blood glucose monitoring systems.
AB  - BACKGROUND: Hepatitis B Immune Globulin (HBIG) is used post liver transplantation
      (OLT) in hepatitis B surface antigen-positive recipients to prevent recurrence of
      hepatitis B. One formulation of HBIG, HepaGam B, contains the disaccharide
      maltose, which can potentially falsely elevate glucose readings when glucose
      nonspecific point of care (GNSPOC) testing is used, such as a glucose
      dehydrogenase pyrroloquinolinequinone (GDH-PQQ)-based method. This can result in
      inappropriate administration of antidiabetic agents and resultant episodes of
      clinically significant hypoglycemia. Glucose specific point of care (GSPOC)
      testing, such as a glucose oxidase-based method, however, is not affected by the
      presence of maltose. The purpose of this study was to determine if there was a
      significant difference in glucose readings using GSPOC and GNSPOC monitoring
      devices after HBIG administration. METHODS: This is a nonrandomized, prospective
      study evaluating patients receiving maintenance HBIG therapy over 3 months post
      liver transplantation. Blood glucose levels in each subject were analyzed by
      GSPOC and GNSPOC devices at specific times around HBIG administration. RESULTS:
      Five adult OLT recipients receiving maintenance HBIG therapy were administered
      HepaGam B during the regularly scheduled outpatient visits. The median difference
      (GNSPOC minus GSPOC) predose as well as immediately, 60 minutes, and 120 minutes
      postdose were: -2, 11, 6, and 0 mg/dL, respectively. A random intercept model was
      used to fit the five subjects' glucose reading data over time. The Meter by Time
      interaction effect was not significant (P = .59) and the Meter effect was not
      significant (P = .46), which demonstrated no statistical difference between GNS
      and GS readings following HBIG administration. CONCLUSIONS: Based on these
      results, there is not a significant difference between GSPOC and GNSPOC readings
      after administration of this HBIG formulation.

PMID- 21168643
TI  - Living-donor liver transplantation in 126 patients with biliary atresia: single
      center experience.
AB  - OBJECTIVES: To describe our experience with 126 consecutive living-donor liver
      transplantation (LDLT) procedures performed because of biliary atresia and to
      evaluate the optimal timing of the operation. PATIENTS AND METHODS: Between May
      2001 and January 2010,126 patients with biliary atresia underwent 130 LDLT
      procedures. Mean (SD) patient age was 3.3 (4.2) years, and body weight was 13.8
      (10.7) kg. Donors included 64 fathers, 63 mothers, and 3 other individuals. The
      left lateral segment was the most commonly used graft (75%). Patients were
      divided into 3 groups according to body weight: group 1, less than 8 kg (n = 40);
      group 2,8 to 20 kg (n = 63); and group 3, more than 20 kg (n = 23). Medical
      records were reviewed retrospectively. Follow up was 4.5 (2.7) years. RESULTS:
      All group 3 donors underwent left lobectomy, and all group 1 donors underwent
      left lateral segmentectomy. No donors required a second operation or died.
      Comparison of the 3 groups demonstrated that recipient Pediatric End-Stage Liver
      Disease score in group 1 was highest, operative blood loss in group 2 was lowest
      (78 mL/kg), and operative time in group 3 was longest (1201 minutes). Hepatic
      artery complications occurred more frequently in group 1 (17.9%), and biliary
      stenosis (43.5%) and gastrointestinal perforation (8.7%) occurred more frequently
      in group 3. The overall patient survival rates at 1, 5, and 9 years was 98%, 97%,
      and 97%, respectively. Five-year patient survival rate in groups 1,2, and 3 were
      92.5%, 100%, and 95.7%, respectively. Gastrointestinal perforation (n = 2) was
      the primary cause of death. CONCLUSIONS: Living-donor liver transplantation is an
      effective treatment of biliary atresia, with good long-term outcome. It seems
      that the most suitable time to perform LDLT to treat biliary atresia is when the
      patient weighs 8 to 20 kg.

PMID- 21168644
TI  - Steroid withdrawal in adult liver transplantation: occurrence at a single center.
AB  - BACKGROUNDS: Steroids are the predominant immunosuppressive agent used after
      liver transplantation even though patients may experience steroid-related side
      effects. AIMS: The objective of this study was to determine whether steroid use
      influenced the outcomes of liver transplantations. METHODS: Three hundred forty
      four adult patients underwent liver transplantation between May 2002 and December
      2007. We reviewed the medical records of these patients, excluding those younger
      than 18 years old or those who died within the first month. The protocol
      withdrawal group (group 1) ceased steroid use within 5 months after
      transplantation, while the late withdrawal group (group 2) continued steroid use
      beyond this 5-month posttransplantation period. RESULTS: All patients were
      classified according to the onset of steroid withdrawal (group 1: n = 243; group
      2: n = 99). The incidences of biopsy-confirmed and treated acute rejection
      episodes (ARE) at 12 and 24 months posttransplantation were 7.8% and 12.3% in
      group 1, but 25.3% and 27.3% in group 2, respectively (P = .001). The incidence
      of hepatitis B virus (HBV) recurrence in group 2 was higher than that in group 1
      (P = .007). The HBV-free survival rates at 1 and 2 years posttransplantation were
      99.0% and 97.1% in group 1 and 96.1% and 92.1% in group 2, respectively. New
      onset diabetes, avascular necrosis of the femoral head, corticosteroid-resistant
      ARE, hepatocellular carcinoma recurrence, as well as graft and patient survivals
      did not differ between the two groups. CONCLUSIONS: Acute rejection episodes and
      HBV recurrence occurred less frequently when steroids were discontinued within 5
      months after liver transplantation.

PMID- 21168645
TI  - Comparison of the affinity column-mediated immunoassay and microparticle enzyme
      immunoassay methods as a tacrolimus concentration assay in the early period after
      liver transplantation.
AB  - OBJECTIVE: We compared the results of 2 immunoassay systems (affinity column
      mediated immunoassay [ACMIA] and microparticle enzyme immunoassay [MEIA]),
      regarding hematologic and biochemical values at 2 weeks after liver
      transplantation. METHODS: We obtained 256 blood samples from 35 patients, at 2
      weeks after liver transplantation, excluding those from patients who were treated
      with interacting medications or renal replacement therapy. We also excluded the
      early mortality cases within 2 weeks of liver transplantation. A Dimension RxL HM
      with the tacrolimus Flex reagent cartilage was used for the ACMIA and the IMx
      tacrolimus II for the MEIA method. RESULTS: The tacrolimus concentrations
      measured by the ACMIA method correlated closely with those measured by the MEIA
      method (r = 0.953). However, the weighted concordance correlation coefficient for
      the repeated-measurement design was 0.74 (95% confidence interval, 0.66-0.85).
      The discrepancies in the tacrolimus level between the 2 methods was large among
      samples with low tacrolimus concentrations especially <5 ng/mL. When the
      difference ratio of the 2 methods ([ACMIA - MEIA]/ACMIA) was analyzed with a
      linear mixed-effects model to identify significant laboratory findings, there
      were no significant differences based on hematocrit, renal function, or hepatic
      function. However, the serum potassium level correlated with the difference ratio
      of the 2 methods (estimated slope, 10.173; P = .02). CONCLUSIONS: Both the ACMIA
      and the MEIA methods are precise; however, the ACMIA method has the advantage of
      fewer pretreatment procedures. In the early liver transplant period, however,
      there was a difference between the serum tacrolimus concentrations measured by
      the 2 methods, especially at a low drug concentrations.

PMID- 21168646
TI  - The use of hepatitis B core antibody-positive donor livers does not appear to
      have a deleterious effect on graft survival in liver transplantation for
      hepatitis C.
AB  - INTRODUCTION: The use of hepatitis B core antibody-positive donor livers
      (HBcAb(+)) has steadily increased. According to a recent multivariate analysis of
      United Network for Organ Sharing (UNOS) data, there was no significant increase
      in the risk of using these donors. The increased risk among the hepatitis C virus
      (HCV)-positive subgroup noted in a univariate model disappeared upon multivariate
      analysis. However, deeper scrutiny may show that HCV-positive recipients may be
      at increased risk with HBcAb(+) donor livers, as they require simultaneous
      treatment with two antiviral regimens there may be deleterious interactions
      between the two viruses. Thus, the issue of HBcAb(+) donors for HCV-positive
      recipients merits more detailed analysis. METHODS: Using UNOS registry data of
      all liver transplantations performed during the Model for End-Stage Liver Disease
      era from February 2002 through November 2007, we analyzed graft survival using
      Kaplan-Meier and Cox regression analyses. RESULTS: Of the 12,543 HCV-positive
      recipients, 2,543 received HBcAb(-) livers and 853 received HBcAb(+) livers.
      While Kaplan-Meier analysis showed significantly lower graft survival among HCV
      negative recipients of HBcAb(+) livers (P = .0001), there was no significant
      effect on graft survival among the HCV-positive population (P = .2). To detect an
      early effect in HCV-positive recipients, we examined 1-year graft survival,
      observing no significant difference (P = .3). To exclude a possible late effect,
      we examined graft survival in the HCV-positive population conditional upon
      surviving at least 1 year after transplantation; no significant difference was
      observed (P = .6). The elimination of potentially confounding codiagnoses, such
      as hepatitis B virus, alcoholism, acute graft failure, and hepatocellular cancer
      did not alter the findings. On univariate analysis, the lack of a significant
      effect persisted among the HCV population. However, the significant effect
      observed in the univariate model for the HCV-negative population became
      insignificant when combined with other risk factors in the multivariate model.
      CONCLUSION: The use of HBcAb(+) livers in recipients with HCV did not appear to
      have a significant impact on graft survival.

PMID- 21168647
TI  - The influence of alcohol abuse history on the differential, longitudinal patterns
      of mental and physical quality of life following liver transplantation.
AB  - This prospective, longitudinal study investigated change in physical and mental
      health quality of life (QoL) in a sample of 65 end-stage liver disease patients
      before and after liver transplantation. Physical and mental health QoL were
      assessed using the SF-36 Physical Health Summary and Mental Health Summary,
      respectively. Baseline data were collected prior to transplant and follow-up data
      were collected at 1 and 6 months after transplantation. Repeated-measures
      analysis of variance results indicate that physical QoL did not improve
      significantly between baseline and 1-month follow-up (F = .031, P = .860) but did
      between 1- and 6-month follow-up (F = 20.873, P < .001). Significant between
      subject effects suggested attenuated improvement for patients with alcohol abuse
      histories (F = 6.213, P = .017). Physical QoL did not improve between 1- and 6
      month follow-up for patients with alcohol abuse history (t((13)) = -1.074, P =
      .112). By contrast, mental health QoL improved significantly between baseline and
      1-month follow-up (F = 13.840, P < .001), but not between 1- and 6-month follow
      up (F = .750, P = .391). No significant differences were found on the Mental
      Health Summary index based on alcohol abuse history for either time period. Post
      hoc multivariate analysis of variance results suggested worse functioning (F =
      2.674, P = .013) for individuals with alcohol abuse history on SF-36 Physical
      Functioning (F = 5.55, P = .021), Body Pain (F = 13.578, P < .001), Vitality (F =
      4.337, P = .040), and Social Functioning (F = 10.50, P = .002) subscales. For
      liver transplant patients, improvements in psychosocial functioning and QoL
      precede improvements in physical QoL. Attenuated physical QoL improvements for
      patients with alcohol abuse histories are related to greater pain and physical
      deficits.

PMID- 21168648
TI  - Predictors of high intraoperative blood loss derived by simple and objective
      method in adult living donor liver transplantation.
AB  - We conducted a risk factor analysis for high intraoperative blood loss (IBL) in
      555 living donor liver transplantation (LDLT) cases with a simple and objective
      method of IBL estimation based on the concept of red cell mass (RCM): Lost RCM
      (mL) = patient's estimated blood volume (mL) * (preoperative hematocrit in % -
      postoperative hematocrit in %) + (transfused leukocyte-depleted red blood cell in
      units * 213 * 70%) + (transfused Cell Saver blood in mL * 55%). Analysis of 33
      preoperative variables revealed that Model for End-stage Liver Disease (MELD)
      score, albumin, the presence of ascites, and previous abdominal surgery were
      correlated with high IBL (lost RCM > 1000 mL) in multivariate logistical
      regression analysis. In conclusion, we found that MELD score, albumin, the
      presence of ascites, and previous abdominal surgery were significantly correlated
      with high IBL during adult LDLT.

PMID- 21168649
TI  - The comparison of the perioperative changes in lactate and prothrombin time
      between deceased versus living donor liver transplantation.
AB  - INTRODUCTION: The present study compared the functional capacity of the grafts by
      evaluating changes in lactate and PT after reperfusion among deceased donor liver
      transplantation (DDLT) versus living donor liver transplantation (LDLT). METHODS:
      We performed a retrospective analysis of primary adult liver transplantations (45
      and 77 recipients in DDLT and LDLT, respectively) between January 2007 and
      December 2009. Lactate was recorded from 5 minutes after reperfusion of graft
      (R0) to intensive care unit admission (P0). PT expressed in international
      normalized ratio (INR) was recorded from R0 to postoperative day (POD) 5. These
      values were compared between two groups. RESULTS: The cold ischemia time (CIT),
      Child-Turcotte-Pugh score, Model for End-stage Liver Disease score, INR, and
      graft-to-recipient weight ratio were greater in the recipients of DDLT versus
      LDLT. Lactate and INR at R0 were similar between the two groups, but, the values
      showed a faster recovery from 1 hour after reperfusion until P0 for lactate and
      until POD 5 for INR among DDLT recipients. The fresh frozen plasma requirements
      during corresponding periods were similar between the two groups. CONCLUSION: The
      functional capacity of the graft measured by changes in lactate and PT after
      reperfusion showed faster recovery among DDLT versus LDLT recipients despite
      poorer graft quality (longer CIT) and the recipients' preoperative medical
      conditions-higher MELD and CTP scores.

PMID- 21168650
TI  - Biliary tract complications after orthotopic liver transplantation: still the
      "Achilles heel"?
AB  - Postoperative biliary tract complications after liver transplantation (LT) still
      lead to early and late morbidity and mortality. Modern interventional endoscopic
      techniques can replace surgical repair as the first line of treatment.
      Nevertheless surgical intervention plays an important role in specific
      situations. We performed a retrospective analysis of patients with biliary
      complications after LT over a 12-year period. We compared treatment programs
      based on duration and success rate. The rate of biliary complications was 24.5%
      (60/245). The side-to-side choledocholedochostomy (CDC) technique showed the
      significantly lowest rate. The rate of complications after hepaticojejunostomy
      (HJS) was considerably lower, albeit not significantly. Eighty-one percent of
      complications after CDC were treated with interventional endoscopy. The duration
      of treatment of strictures, was 10 times greater than that of leakages. Surgical
      repair was necessary for 19% of complications occurring after CDC. The treatment
      options after HJS largely comprised surgical repairs. From a surgical standpoint,
      choosing the correct method for biliary reconstruction and ensuring normal
      arterial flow are the best preventive techniques to avoid biliary complications.
      Over the past 10 years, the primary treatment regimen has moved from surgical
      repair to interventional endoscopy. Only when endoscopy fails, should one
      consider surgical repair. The treatment after HJS is still primarily surgical.
      Percutaneous transhepatic approaches should be avoided. Creation of an inspection
      stoma to allow endoscopic access is an option.

PMID- 21168651
TI  - The effects of gabexate mesilate on the microsurgical reconstruction of the
      hepatic artery in living donor liver transplantation.
AB  - OBJECTIVES: Microsurgical reconstruction of hepatic artery is essential but
      require challenging techniques especially for living donor liver transplantation
      (LDLT), because the recipient artery is short, located deep, and usable vessel
      grafts are limited. Furthermore, hepatic artery thrombosis (HAT) can be a lethal
      complication. Therefore, we began the systemic administration of gabexate
      mesilate, a strong serine protease inhibitor. It has often been effective to
      treat disseminated intravascular coagulation. The purpose of this study was to
      examine the effects of gabexate mesilate on the microvascular reconstruction.
      METHODS: From 1991 to 2009, we performed 134 microsurgical reconstructions of
      LDLT. This retrospective investigation of those cases divided them into four
      groups: group I, anticoagulation with heparin (n = 3); group II, heparin and
      gabexate mesilate (20 mg/kg/d; n = 26); group III, heparin and full-dose gabexate
      mesilate (40 mg/kg/d; n = 72); and group IV, full-dose gabexate mesilate alone (n
      = 33). Groups I and II were mainly pediatric cases (left lobe grafts only);
      groups III and IV, adult cases (left: right = 57:48). Using ultrasonography to 14
      days, we investigated HAT by examining pulsatile index, resistive index, and
      acceleration time. RESULTS: HAT occurred in groups I, II, III, and IV at 33.3%
      (1/3), 11.5% (3/26), 6.9% (5/72), and 0% (0/33), respectively. The 5-year
      survival rates of groups III + IV versus groups I + II were 82.4% and 71.1%,
      respectively (P < .05). In HAT cases, even before the event the acceleration
      times were delayed to over 100 milliseconds. CONCLUSION: Gabexate mesilate
      administration was safe for and protective of microvascular reconstructions in
      LDLT.

PMID- 21168652
TI  - Use of the hilar plate looping technique for bile duct dissection in living donor
      liver transplantation significantly reduces recipient biliary complications.
AB  - Biliary complications remain a major cause of morbidity after liver
      transplantation, especially in living donor liver transplantation (LDLT).
      Maintaining adequate blood supply to the bile duct is important for the
      prevention of biliary complications. The objective of this study was to analyze
      the effects of different techniques for bile duct anastomosis on
      posttransplantation biliary complications. From August 2005 to August 2008, 121
      liver transplantations were performed at our center. Among the total 121 liver
      transplant recipients, 68 patients underwent a LDLT using a right lobe graft and
      were enrolled in this study. We used classic dissection for the first 38
      recipients and the hilar plate looping technique for the next 30 patients. The
      hilar plate looping technique involves the looping of the complete hilar plate
      and Glissonian sheath around the hepatic duct after full dissection of the right
      hepatic artery and portal vein. Biliary complications were defined as bilomas or
      strictures that developed within 6 months after transplantation and required
      surgical or radiological intervention. There were no significant demographic
      differences between the 2 groups. The incidence of complications was 15 (39.5%)
      for classic dissection and 3 (18.8%) for hilar plate looping. Furthermore, there
      were no biliary strictures in the hilar plate looping group, and there was a
      significant difference in the complication rate between the 2 groups (P = .011).
      In conclusion, the hilar plate looping technique during LDLT significantly
      reduces recipient biliary complications.

PMID- 21168653
TI  - Postoperative bleeding after AB0-incompatible living donor kidney
      transplantation.
AB  - BACKGROUND: Since 2007, we have performed 14 AB0-incompatible (AB0i) living
      kidney transplantations to increase the number of living kidney transplantations.
      METHODS: To prevent clotting, donor kidneys were perfused with an HTK/heparin
      solution with heparin washed out immediately pretransplantation. However, in 4/14
      recipients, significant postoperative diffuse hemorrhage occurred with the need
      for surgical intervention in 3 patients. To analyze the cause of postoperative
      diffuse bleeding, sequentially before and after opening the graft anastomosis, we
      prospectively performed coagulation studies: partial thromboplastin time (PTT),
      thrombin time, thromboplastin time, fibrinogen, antithrombin, D-dimers,
      plasminogen, and thrombelastography. RESULTS: We found no clotting disturbances
      owing to blood group-specific immunoadsorption. However, 3/4 patients with
      bleeding complications showed elevated PTT values even 2 hours after opening the
      anastomosis, which was proven to be a heparin effect by in vitro application of
      heparinase. Hyperfibrinolysis and disturbances of platelet aggregation were not
      detected. Because of these results, we lowered the heparin dose administered
      after donor nephrectomy from initially 10,000-20,000 to 4000 IU resulting in
      significantly lower PTT values at 2 hours (34.6 +/- 4.5 s among patients 6-14 vs
      69.0 +/- 16.3 s among patients 1-5; P = .012). There were no further bleeding
      complications. Lowering the heparin dosage had no impact on graft function: serum
      creatinine at discharge of 1.5 +/- 0.1 versus 1.6 +/- 0.2 mg/dL. CONCLUSION: Our
      data indicated that postoperative hemorrhage after AB0i kidney transplantation
      was associated with the amount of heparin used for graft perfusion after donor
      nephrectomy. The use of antifibrinolytic agents may be harmful; no
      hyperfibrinolysis takes place in the AB0i transplant setting.

PMID- 21168654
TI  - Survival after liver transplantation in patients who develop renal insufficiency.
AB  - BACKGROUND: Renal insufficiency (RI) after liver transplantation (OLT) is
      associated with worse outcomes but the actual survival after RI ensues is not
      well described. We examined the survival of OLT recipients who developed moderate
      or severe RI or end-stage renal disease (ESRD), seeking to identify variables
      associated with these outcomes. METHODS: Between 1993 and 2007, 731 patients
      underwent OLT. After excluding patients undergoing retransplantation, combined
      kidney-liver grafts, and those who died within 1 year, we had a cohort of 527
      subjects whose basic demographic data were obtained. Glomerular filtration rate
      (GFR) calculated (by MDRD4-Modification of Diet in Renal Disease 4-formula) at 3
      month intervals in the first year and then at 6-month intervals. Moderate RI was
      defined as a GFR < 60 mL/min/1.73 m(2); severe RI, GFR < 30; and ESRD by need for
      dialysis or renal transplantation. We determined survival from the point of
      developing RI. An analysis determined factors associated with survival. RESULTS:
      Among 527 patients, 251 developed moderate (47.6%) and 40 (7.6%) severe RI as
      well as 40 (7.6%) with ESRD. Once RI ensued, the 5-year survivals for patients
      with moderate RI, severe RI or ESRD were 84.0%, 67.7%, and 48.5%, respectively.
      Five-year survival, for patients receiving a renal transplant was 100%. On
      multivariate Cox regression analysis, the only variables associated with time to
      death for patients with any RI were higher age at transplant (hazard ratio [HR] =
      1.04, P = .02), higher creatinine at transplant (HR = 1.25, P = .01),
      pretransplant diabetes (HR = 2.34, P = .008), and transplantation in the Model
      for End-stage Liver Disease (MELD) era (HR = 0.15, P = .002). CONCLUSION:
      Development of severe RI or ESRD correlated with diminished survival. For
      patients with RI, age and creatinine at transplant, pretransplant diabetes, and
      transplantation in the pre-MELD era were associated with lower survival rates.
      Five-year survival for dialysis patients was somewhat higher than that previously
      reported but worse than that of subjects treated by renal transplantation.

PMID- 21168655
TI  - Rifle criteria for acute kidney dysfunction following liver transplantation:
      incidence and risk factors.
AB  - RIFLE criteria have been used to determine the incidence of acute kidney
      dysfunction (AKD) after orthotopic liver transplantation (OLT). However, no
      studies have focused on the incidence of AKD after OLT in patients with normal
      pre-OLT kidney functions. Using the RIFLE criteria, we determined the incidence
      and risk factors for AKD after OLT in patients with normal pre-OLT kidney
      function. We retrospectively analyzed the records of 112 patients who underwent
      OLT from January 2000 to February 2009 with normal prior kidney function. We
      investigated three levels of renal dysfunction outlined in the RIFLE criteria:
      risk (R); injury (I); and failure (F). Preoperative, intraoperative, and
      postoperative variables were collected. AKD occurred in 64 (57%) OLTs with risk,
      injury, and failure frequencies of 19%, 11%, and 28%, respectively. Compared with
      those who did not develop AKD postoperatively, those who did had significantly
      higher MELD scores (19 +/- 7 vs 16 +/- 8; P = .018), more frequently use of
      inotropic agents intraoperatively (54% vs 35%; P = .070), more colloid treatment
      (300 +/- 433 mL vs 105 +/- 203 mL; P = .007), longer anhepatic phase (88.0 +/-
      42.0 minutes vs 73.0 +/- 20.0 minutes; P = .037), and a greater incidence of
      intraoperative acidosis (64% vs 44%; P = .047). Logistic regression analysis
      revealed that MELD score (odds ratio 1.107, 95% CI 1.022-1.200, P = .013),
      duration of anhepatic phase (odds ratio 1.020 95% CI 1.000-1.040, P = .053), and
      intraoperative acidosis (odds ratio 0.277 95% CI 0.093-0.825 P = .021) were
      independent risk factors for AKD. In conclusion, our results suggested that,
      based on RIFLE criteria, AKD occurs in more than half of OLTs postoperatively. A
      higher MELD score, longer anhepatic phase, and occurrence of intraoperative
      acidosis were associated with AKD.

PMID- 21168656
TI  - The impact of donor race on recurrent hepatitis C after liver transplantation.
AB  - BACKGROUND: Several studies have demonstrated mixed results regarding the
      influence of donor race on patient and graft survival in patients infected with
      hepatitis C virus (HCV) after liver transplant. However, few studies have looked
      at the impact of donor race on recurrent HCV. This study is a retrospective
      analysis of the influence of patient and donor race on the severity of recurrent
      HCV at a single center. METHODS: Of patients transplanted at our center between
      2000 and 2006, 222 were infected with HCV. Of these, 165 were eligible to be
      evaluated for recurrent HCV after transplant. We excluded those with patient and
      graft loss within 1 year that was not related to recurrent HCV, patients with
      advanced fibrosis from other causes, those who did not undergo posttransplant
      liver biopsy, and those lost to follow-up. Patients were given a recurrent HCV
      score of 1, 2, or 3. A score of 1 was assigned if the patient had no more than
      mild portal fibrosis at 1 year and no bridging fibrosis at any point. A score of
      2 was defined as moderate portal fibrosis or focal bridging fibrosis at 1 year or
      bridging fibrosis or cirrhosis after 3 years. A score of 3 was defined as
      bridging fibrosis, cirrhosis, or graft loss from HCV within 3 years. Baseline
      characteristics including donor and recipient age, race, sex, body mass index,
      ischemia time, hypertension, and diabetes were recorded. Analysis was performed
      with ordinal multivariate logistic regression modeling. RESULTS: Of the 165
      patients with a recurrent HCV score, 105 (64%) had a score of 1, 29 patients
      (17%) had a score of 2, and 31 patients (19%) had a score of 3. In all, 132
      recipients (80%) had white donors, and 26 (16%) had African American donors, 115
      patients (70%) were white and 40 (24%) were African American. The mean recurrent
      HCV scores for the patient donor and recipient race combinations are as follows:
      white donor and white recipient, 1.54; white donor and African American
      recipient, 1.89; African American donor and white recipient, 1.18; and African
      American donor and African American recipient, 1.23. Having a white donor also
      significantly associated with a higher recurrent HCV score regardless of
      recipient race (odds ratio 2.93, P = .044) in African American patients, having a
      white donor had an odds ratio of 4.62 (P = .046). After adjusting for donor age
      and sex and patient age and sex, having a white donor was still found to be
      associated with a higher recurrent HCV score (4.48, P = .0275) on multivariate
      analysis. For all 222 patients, donor race was not associated with overall
      patient and graft survival. CONCLUSION: Patients receiving white donor grafts had
      significantly worse recurrent HCV than those receiving grafts from African
      American donors regardless of recipient race. This difference was especially
      marked in African American recipients and persisted on multivariate analysis.
      These data suggest a graft from a white donor is potentially one more important
      variable in identifying patients at risk for more aggressive recurrent HCV after
      orthotopic liver transplant.

PMID- 21168657
TI  - Epstein-Barr virus infection after pediatric living-related liver transplantation
      -management and risk factors.
AB  - INTRODUCTION: Posttransplant lymphoproliferative disorder (PTLD) is one of the
      severe complications after pediatric liver transplantation. Epstein-Barr virus
      (EBV) infection is a major risk factor developing PTLD. This study evaluates the
      risk factors, incidence, and clinical presentation of EBV infection at our
      institute. PATIENTS AND METHODS: This study examines 81 children who underwent
      living-related liver transplantation (LRLT) from November 2005 to December 2009.
      The immunosuppression protocol consisted of tacrolimus and low-dose steroids,
      which were withdrawn by 3 months after LRLT. Additional immunosuppression was
      indicated for the selected cases because of recurrent rejection or renal
      insufficiency. Fifteen ABO blood type incompatible LRLTs were enrolled into this
      study. EBV was periodically monitored by the use of a real-time quantitative
      polymerase chain reaction (cut-off value, >10(2) copies/MUg DNA). The median
      follow-up period was 637 days (range, 85 to 1548 days). These patients were
      divided into two groups: EBV infection versus EBV noninfection, for analysis of
      risk factors by univariate analysis. RESULTS: The incidence of EBV infection was
      50.6% (n = 41) with the mean onset of 276 +/- 279 postoperative days (range, 7 to
      1229 days). Nine cases (22.5%) presented clinical symptoms related to EBV
      infection, consisting of adenoid hypertrophy (n = 5), Evans's syndrome (n = 2),
      hemophagocytic syndrome (n = 1), and erythema nodosum (n = 1). There was no case
      of PTLD. The combination of a preoperative EBV seropositive donor and an EBV
      seronegative recipient was a high risk factor for postoperative EBV infection
      among the recipients (56.1% versus 26.8%, P < .05). The mean age at operation
      among the EBV infection group was younger than that of the EBV noninfection group
      (22 +/- 30 months versus 62 +/- 68 months; P < .05). The incidence of acute
      rejection episodes and cytomegalovirus infections; ABO blood type incompatible
      LRLT, and the length of steroid treatment and the additional immunosuppression
      were not significantly different between the two groups. CONCLUSION: There were
      various clinical presentations related to EBV infection; however, none of our
      patients developed PTLD. Careful monitoring of EBV infection especially for cases
      with donor seropositivity is important to prevent disease progression.

PMID- 21168658
TI  - The impact of postoperative infection on long-term outcomes in liver
      transplantation.
AB  - INTRODUCTION: Postoperative infection (POI) prolongs inpatient stay, delays
      return to normal activity, and may be detrimental to long-term survival after
      cancer resections. This study sought to identify the impact of postoperative
      infection on liver transplantation outcomes. METHODS: We analyzed our prospective
      database of 910 adult patients who underwent liver transplantation between 2000
      and 2010 in a single UK center. POI was defined as pyrexia plus positive cultures
      from blood, sputum, urine, wound, or ascitic fluid. Patient demographic features
      and perioperative variables were analyzed for their effects on POI. The impacts
      of POI on overall survival (OS) and graft survival were analyzed using Kaplan
      Meier curves with log-rank tests for significance, before entry into a
      multivariate regression analysis. We analyzed the effects of POI on the length of
      hospital stay (LOS) and the incidence of acute rejection episodes and
      readmissions within 1 year as secondary outcomes. RESULTS: Patients who developed
      a postoperative chest or wound infection showed poorer OS at a mean of 7.0 versus
      8.8 years (P = .009) and 7.0 versus 8.8 years (P = .003), respectively. Infection
      in blood, ascitic fluid, or urine showed no significant impact on survival. LOS
      was significantly increased among patients with a wound (median 21 vs 17 days, P
      = .011), a sputum (median 24 vs 17 days, P < .001), or a blood infection (median
      32 vs 17 days, P < .001). Higher rates of intraoperative blood transfusion were
      observed among subjects who developed a chest or a wound infection. There was no
      difference in other variables between those who did versus did not develop an
      infection. Upon multivariate analysis, wound infection was the strongest
      independent predictor of OS (P = .007). CONCLUSION: We demonstrated that wound or
      chest infections were associated with poorer OS. More aggressive prophylactic
      and/or therapeutic interventions targeting specific sites of infection may
      represent a simple and cost-effective measure to reduce hospital stay and improve
      OS.

PMID- 21168659
TI  - Correlations between A/H1N1 influenza and acute cellular rejection in liver
      transplantation patients.
AB  - INTRODUCTION: Influenza is a common cause of respiratory infection in transplant
      recipients. It is expected that A/H1N1 influenza virus causes more severe disease
      in solid-organ recipients. Our goal was to describe two A/H1N1 infections that
      occurred after Orthotopic liver transplantation followed by acute allograft
      rejection episodes. CASE REPORTS: From March 2009 to March 2010 we observe two
      liver transplant patients with symptoms suggestive of A/H1N1 infection. The
      diagnosis was out based on a temperature of 37.8 degrees C (100 degrees F) or
      higher and the presence of a cough or using materials from anasopharyngeal and
      oropharyngeal swabs a sore throat. The diagnosis was confirmed by viral RNA
      detection by real-time reverse-transcriptase-polymerase-chain-reaction assay (RT
      PCR) using materials from nasopharyngeal and oropharyngeal swabs. We performed
      the RT-PCR assay for A/H1N1 detection in a liver biopsy from one patient. Both
      patients were treated with usual doses of oseltamivir (75 mg twice daily for 5
      days). One patient developed acute bacterial sinusitis requiring antibiotic
      therapy. Thereafter the liver enzymes increased and transplant biopsies showed
      moderate-to-severe acute cellular rejection. They were treated with
      corticosteroids. The liver enzymes normalized after 3 months. CONCLUSION: A/H1N1
      influenza can lead to a severe acute cellular rejection episode with
      corticosteroid resistant treatment in liver transplant patients. Transplant
      centers should be aware of a possible relationship between A/H1N1 infections and
      acute allograft rejection episodes.

PMID- 21168660
TI  - Procalcitonin in the setting of complicated postoperative course after liver
      transplantation.
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) is a treatment for end-stage
      liver disease. The shortage of available organs leads to the acceptance of
      marginal grafts, thereby increasing the risk of perioperative complications such
      as acute rejection, infection, and graft dysfunction Procalcitonin (PCT) has been
      shown to be a reliable marker for a complicated course after traumatic injury as
      well as in the courses of systemic inflammatory response syndrome and sepsis. The
      aim of our study was to evaluate PCT as an early prognostic marker for the
      occurrence of complication during the postoperative course after OLT. METHOD: We
      analyzed PCT levels and clinical and paraclinical data of 32 patients who
      underwent 33 OLTs. The highest PCT was termed as peak-PCT. Patients were
      stratified into noncomplication and complication groups. Renal replacement
      therapy, respiratory insufficiency, postoperative bleeding, refractory ascites,
      pleural effusion, rejection, sepsis, and fatal outcome were defined as
      complications. A secondary stratification, using a peak-PCT of 5 ng/mL, was used
      to analyzed the risk of a complication. We also analyzed the course of PCT after
      OLT in each group. RESULTS: The peak-PCT, which occurred between the first and
      third postoperative day in 30 patients, was followed by halving of the value
      every second day. Three subjects died because of sepsis. A constantly rising PCT
      or a secondary rise observed in 2 patients was associated with a fatal outcome.
      The noncomplication group included 18 patients, 8 of them showing a peakPCT <5
      ng/mL and 10 above. The complication group included 14 patients who underwent 15
      transplantations; Only 1 displayed a peakPCT <5 ng/mL. When the peak-PCT was >5
      ng/mL, the odds ratio of a complication was 11.2 (95% Confidence interval, 10.81
      11.59; P < .025). However, not before the 7th postoperative day was the course of
      mean PCT levels significantly different between the complication and
      noncomplication groups. In transplant patients, an elevation of PCT was observed
      only in the presence of bacterial infection and not rejection or wound infection.
      PCT rose during respiratory failure and sepsis, but not renal replacement
      therapy, ascites, pleural effusion, rejection, or bleeding. CONCLUSION: PCT was a
      reliable marker. A decline was observed in 31 cases with subject, who both had
      fatal outcomes showing a constantly rising level. An initial high PCT indicated a
      poor prognosis; some members of the noncomplication group also had levels >15
      ng/mL. The patients in the complication group showed a higher mean PCT, which was
      significant at 7 days, most probably because of the high variation among levels.
      Still, a peak-PCT >5 ng/mL showed an odds ratio of 11.2 for patients to
      experience a complication.

PMID- 21168661
TI  - Noncompliance with medications in pediatric patients after living-donor liver
      transplantation.
AB  - INTRODUCTION: Noncompliance with immunosuppressant therapy is a serious problem
      that leads to the possibility of graft rejection, even in the long term after
      liver transplantation. The objectives of the present study were to review and
      describe features of patient noncompliance after living-donor liver
      transplantation (LDLT). PATIENTS AND METHODS: Among pediatric patients (age <18
      years) surviving more than 5 years after LDLT, noncompliant patients were
      identified, and their clinicopathologic characteristics were studied
      retrospectively. RESULTS: Of 108 pediatric recipients who survived more than 5
      years after LDLT, 6 female patients (5.6%) were noncompliant. Median (range) age
      at transplantation was 5 (2-15) years, and at noncompliance was 18 (9-21) years.
      Median time to noncompliance after transplantation was 8 (5-16) years. The 6
      noncompliant patients received increased immunosuppression therapy, and liver
      function test results improved. Noncompliance was improved via intervention with
      medication, but recurred in 2 patients (33%). Noncompliance did not result in
      graft or patient loss. CONCLUSION: The prevalence of noncompliance was not so
      high in LDLT recipients. Liver dysfunction secondary to noncompliance improved
      with increased immunosuppression therapy.

PMID- 21168662
TI  - Simultaneous kidney-pancreas transplantation for end-stage renal disease patients
      with insulin-dependent diabetes and detectable C-peptide.
AB  - INTRODUCTION: There is controversy regarding the place of simultaneous pancreas
      kidney (SPK) transplantation in end-stage renal disease (ESRD) patients with
      insulin-dependent diabetes mellitus (IDDM) and detectable c-peptide. We sought to
      compare outcomes of recipients with and without pretransplantation c-peptide.
      METHODS: This retrospective single-center review included consecutive primary SPK
      transplantations performed between September 2007 and May 2010. Demographic
      characteristics and outcomes were compared between recipients with and without
      pretransplantation c-peptide. RESULTS: Seven of 25 (28%) consecutive SPK
      transplant recipients with a diagnosis of IDDM and ESRD had detectable c-peptide
      prior to transplantation. The mean c-peptide level was 6.3 +/- 6.1 ng/mL. For
      those recipients with and without c-peptide, mean age at diagnosis of IDDM (12.4
      +/- 7.8 vs 17.1 +/- 6.6 years; P = not significant [NS]), duration of IDDM prior
      to transplantation (30 +/- 10 vs 23 +/- 9 years; P = NS), and body mass index
      (25.9 +/- 4.5 vs 26.7 +/- 4.5 kg/m(2); P = NS) were equivalent between the
      groups. With a median follow-up of 17 months (range, 3-35 months) there was 1
      graft loss (due to cardiovascular death) among the 25 patients. At the most
      recent follow-up, for recipients with and without c-peptide, both the mean serum
      creatinine (1.3 +/- 0.6 vs 1.0 +/- 0.2 ng/mL; P = NS) and the mean HbA1c level
      (5.3 +/- 0.4 vs 5.3 +/- 0.5; P = NS) were equivalent between the groups.
      CONCLUSION: For nonobese ESRD patients diagnosed with IDDM at a young age, the
      presence of detectable c-peptide should not influence the decision to proceed
      with SPK transplantation.

PMID- 21168663
TI  - Factors influencing outcome of simultaneous kidney and pancreas transplantation:
      a 23-year single-center clinical experience.
AB  - INTRODUCTION: Simultaneous kidney and pancreas transplantation (SKPT) has become
      an effective treatment for patients who have diabetes mellitus type I with
      advanced nephropathy. This study assesses the progress of the SKPT program at
      Uppsala University Hospital, Sweden, and evaluates prognostic factors for graft
      survival. MATERIALS AND METHODS: Between February 1986 and September 2009, we
      performed 113 SKPT. The immunosuppression protocols changed over time and are
      defined as era 1, cyclosporine (CyA), atzathioprine (AZA) and steroids (C/A/S);
      era 2, C/A/S with antithymocyte globulin (ATG) induction (C/A/S/A); era 3, CyA,
      mycophenolate mofetic (MMF), steroids and ATG induction (C/M/S/A); era 4,
      tacrolimus (TAC), MMF, steroid, and ATG induction (T/M/S/A) and era 5, TAC, MMF,
      steroids and basiliximab induction (T/M/S/B). We analyzed
      donor/recipient/operative and postoperative variables to assess their influence
      on pancreas graft and patient survivals. RESULTS: The overall 1-, 5-, and 10-year
      patient survivals were 95.5%, 84.1%, and 65.5%, respectively. The 1-, 5-, and 10
      year overall pancreas graft survivals were 77.6%, 58.4%, and 48.4%. The 1-, 5-,
      and 10-year pancreas graft survivals in SKPT patients transplanted between
      October 1997 and September 2009. (T/M/S/A and T/M/S/B; eras 4 and 5) were 95.3%,
      72.7%, and 63.1%, respectively, which was significantly better than those of
      patients transplanted between February 1986 and September 1997 (era, 1 through 3)
      (P < 0.01, P < 0.0001, respectively). The quadruple regimen with TAC and MMF
      (eras 4 and 5) decreased the incidence of acute rejection episodes compared with
      eras 1 through 3 (P < 0.0001). Basiliximab induction (T/M/S/B; era 5) reduced the
      CMV infection rate compared with eras 1 through 4 (P < 0.01). Multivariate
      analysis revealed that donor age (younger than 40 years), immunosuppressive
      regimen with TAC and MMF (eras 4 and 5), and absence of acute rejection episodes
      independently affected pancreas graft survival. CONCLUSIONS: We demonstrate a
      superiority of the quadruple protocol with T/M/S/B for graft and patient survival
      with a decreased incidence of CMV infection after SKPT.

PMID- 21168664
TI  - Can the preprocurement pancreas suitability score predict ischemia-reperfusion
      injury and graft survival after pancreas transplantation?
AB  - BACKGROUND: Ischemia-reperfusion injury (IRI) is common after pancreas
      transplantation, leading to pancreatitis or thrombosis with the need for
      relaparotomy or even graft loss. Optimal donor selection may reduce the
      postoperative morbidity of IRI. The Eurotransplant preprocurement pancreas
      suitability score (P-PASS) seeks to identify ideal donors with a value <17. Owing
      to the organ shortage the waiting time for pancreas transplantation is
      increasing, a problem that may be addressed with the use of extended-criteria
      donors. We analyzed our pancreas transplantations regarding postoperative
      complications according to the P-PASS. To reflect IRI we used the peak C-reactive
      protein (CRP) levels during the first 3 postoperative days. METHODS: From January
      2009 to July 2010, we transplanted 52 pancreas grafts, including, 50 simultaneous
      pancreas-kidney transplantations (SPK), 1 after a kidney graft, and 1 alone. For
      3 SPK donors the P-PASS was not available. All transplantations were performed
      using systemic venous and enteric drainage. The immunosuppression protocol
      included antibody induction with antithymocyte globulin and maintenance therapy
      with steroids, tacrolimus, and mycophenolate mofetil. The peak CRP in the first 3
      postoperative days was used as a marker for IRI. RESULTS: The mean P-PASS of our
      donors was 16.4 +/- 2.6 (range, 12-22). We compared 24 patients receiving organs
      from "ideal" donors (P-PASS <17; ID) with 25 receiving grafts from extended
      criteria donors (P-PASS >=17; ED). There was no significant difference in the
      incidence of graft loss among ID versus ED grafts (20.8% vs 20.0%; P = 1.0).
      Comparing the rates of postoperative complications of patients, we did not
      observe a significant difference in graft thrombosis (4.2% vs 16.0%; P = .349),
      relaparotomy (29.2% vs 40.0%; P = .551), a pancreatic fistula (37.5% vs 28.0%; P
      = .543), or the length of hospital stay (36.5 +/- 19.2 vs 37.4 +/- 20.8 days; P =
      .875), respectively. Regarding IRI, there was no significant difference in peak
      CRP values (14.1 +/- 5.5 vs 16.2 +/- 6.0 mg/dL; P = .211). CONCLUSION: This
      single center analysis failed to show that P-PASS significantly predicted
      pancreas graft survival, postoperative morbidity, or IRI severity. These findings
      suggested a chance to increase the donor pool using extended-criteria donors.

PMID- 21168665
TI  - Incidence and treatment of pancreatic fistula after simultaneous pancreas kidney
      transplantation.
AB  - BACKGROUND: Simultaneous pancreas and kidney transplantation (SPK) is associated
      with great postoperative morbidity, including the need for relaparotomy in up to
      40% of cases. Because the pancreatic graft is known to be the major cause of the
      high morbidity, we examined the incidence and treatment of pancreatic fistula
      (PF) in this retrospective analysis. METHODS: From January 2004 to July 2010, we
      transplanted 52 pancreas grafts, including 50 SPK, 1 pancreas after kidney, and 1
      pancreas transplantation alone. There were 22 female and 30 male patients with an
      overall mean age of 42.4 +/- 7.4 years. The mean duration of diabetes was 27.3 +
      8.1 years, mean duration of dialysis was 24.2 +/- 28.6 months, and 14 cases were
      pre-emptive transplantations. All procedures were performed using systemic venous
      and enteric drainage. RESULTS: The incidence of clinically relevant PF was 16/52
      (30.8%), including 11 (68.8%) that were treated conservatively with a drain. Five
      patients (31.2%) needed relaparotomy: 2 due to enteric leakage, 2 due to acute
      abdominal pain with graft pancreatitis observed at laparotomy, and 1 due to acute
      hemorrhage. In 3 cases, graft pancreatectomy was necessary. Comparing the
      patients with (PF+) versus without (PF-) fistulas, there was no significant
      difference in cold ischemia time (10.9 +/- 2.6 hours vs 10.4 +/- 4.4 hours; P =
      .633), donor age. We found a significantly higher peak C-reactive protein (CRP)
      level in the patients with pancreatic fistula (3661.4 +/- 3474.8 U/L vs 821.8 +/-
      1293.7 U/L, P = .022). The lipase concentration measured in the drainage fluid
      postoperatively showed a significant difference between the 2 groups (3661.4 +/-
      3474.8 U/L vs 821.8 +/- 1293.7 U/L; P = 0.006). Also, the amylase concentration
      was higher in the PF+ group (1747.3 +/- 3346.7 U/L vs 265.3 +/- 254.9 U/L; P =
      .097). Graft loss occurred in 4/16 cases (25.0%) of PF+ and 7/36 (19.4%) of PF-
      (P = .719). CONCLUSION: The incidence of PF after pancreas transplantation is
      high and seems to be associated with ischemia-reperfusion injury reflected by
      peak-CRP. In most cases a conservative treatment is successful. The occurrence of
      a PF does not significantly impair graft survival.

PMID- 21168666
TI  - Surgical protocol involving the infusion of paramagnetic microparticles for
      preferential incorporation within porcine islets.
AB  - INTRODUCTION: Despite significant advances, widespread applicability of islet
      cell transplantation remains elusive. Refinement of current islet isolation
      protocols may improve transplant outcomes. Islet purification by magnetic
      separation has shown early promise. However, surgical protocols must be optimized
      to maximize the incorporation of paramagnetic microparticles (MP) within a
      greater number of islets. This study explores the impact of MP concentration and
      infusion method on optimizing MP incorporation within islets. METHODS: Five
      porcine pancreata were procured from donors after cardiac death. Splenic lobes
      were isolated and infused with varying concentrations of MP (8, 16, and 32 *
      10(8) MP/L of cold preservation solution) and using one of two delivery
      techniques (hanging bag versus hand-syringe). After procurement and infusion,
      pancreata were stored at 0 degrees C to 4 degrees C during transportation (less
      than 1 hour), fixed in 10% buffered formalin, and examined by standard magnetic
      resonance imaging (MRI) and histopathology. RESULTS: T2*-weighted MRI showed
      homogeneous distribution of MP in all experimental splenic lobes. In addition,
      histologic analysis confirmed that MP were primarily located within the
      microvasculature of islets (82% to 85%), with few MP present in acinar tissue
      (15% to 18%), with an average of five to seven MP per islet (within a 5-MUm thick
      section). The highest MP incorporation was achieved at a concentration of 16 *
      10(8) MP/L using the hand-syringe technique. CONCLUSION: This preliminary study
      suggests that optimization of a surgical protocol, MP concentrations, and applied
      infusion pressures may enable more uniform distribution of MP in the porcine
      pancreas and better control of MP incorporation within islets. These results may
      have implications in maximizing the efficacy of islet purification by magnetic
      separation.

PMID- 21168667
TI  - Actions of the Japanese Pancreas and Islet Transplantation Association regarding
      transplanted human islets isolated using Liberase HI.
AB  - PURPOSE: The potential for introducing transmissible spongiform encephalopathy
      (TSE) into islet cells was indicated by recognizing that Liberase HI is isolated
      from Clostridium histolyticum grown in media containing brain-heart infusion
      broth. A national team within the Japanese Pancreas and Islet Transplantation
      Association implemented an islet transplantation program in Japan using Liberase
      HI. The program comprised 65 islet isolations from non-heart-beating donors and
      34 transplants into 18 patients. Herein, we have summarized how the Association
      followed these recipients over the long term. PROCEDURES: We established an ad
      hoc committee to follow recipients transplanted with islets isolated using
      Liberase HI after becoming informed of the associated dangers of using this
      enzyme. We also stopped islet transplantations using Liberase. The committee
      addressed the major concerns of the risk of the collagenase being contaminated
      with TSE and of the recipient follow-up. All recipients were examined by
      diffusion MRI and EEG and then scheduled for evaluation and follow-up by
      specialists in Creutzfeldt-Jakob disease (CJD). Bioassays of bovine spongiform
      encephalopathy prions in the enzyme proceeded using knock-in mice expressing
      bovine prion protein. These assays could detect contaminating prions at a
      dilution of 1 * 10(4). After inactivating its collagenase activity, Liberase HI
      was injected into the abdominal cavities of knock-in mice. Four months later,
      prion infectivity in Liberase HI was evaluated by immunohistochemical staining
      and Western blotting of spleen homogenates using anti-prion protein antibodies.
      MAIN FINDINGS: Western blotting and immunohistochemical staining did not detect
      prions in Liberase HI. Diffusion MRI and EEG evaluations performed by CJD
      specialists confirmed that none of the transplanted recipients had CJD.
      CONCLUSIONS: Three years of follow-up revealed that none of the Japanese
      recipients of islet transplants developed CJD. Prion bioassays showed that the
      Liberase HI used to isolate islets for transplantation was free of infectious TSE
      prions.

PMID- 21168668
TI  - Magnetic resonance imaging study of mouse islet allotransplantation.
AB  - Although only 10% of islet transplant recipients maintain insulin independence,
      80% of them are C-peptide positive at 5 years. To better understand the fate of
      transplanted islets, a magnetic resonance imaging (MRI) technique has been used
      to detect superparamagnetic iron oxide (SPIO)-labeled transplanted islets.
      Recently, we successfully used a novel MRI contrast agent, chitosan-coated SPIO
      (CSPIO) nanoparticles, to monitor mouse islet isografts for 18 weeks after
      transplantation. In the present study, we tested whether CSPIO could be applied
      to monitor islet allografts, which are supposedly rejected without immune
      interventions. Male C57BL/6 and Balb/c mice were used as donors and recipients of
      islet transplantation, respectively. After overnight incubation with or without
      CSPIO (10 MUg/mL), 300 C57BL/6 islets were transplanted under the left kidney
      capsule of each Balb/c mouse. Starting from day 10 after transplantation, 3.0
      Tesla MRI of the recipients was performed weekly. Four mice were followed for
      >=38 days. At 38 and 45 days, 1 islet graft was removed for insulin and Prussian
      blue staining, respectively. From days 10 to 45 after transplantation, CSPIO
      labeled islet grafts were visualized on MRI scans as sustained distinct
      hypointense spots homogeneously located at the upper pole of left kidney, the
      site of transplantation. At days 38 and 45, the histology of CSPIO-labeled islet
      grafts revealed insulin and iron staining colocalized in the same areas. Our
      results in a mouse allotransplantation model indicated that CSPIO-labeled islets
      survived as long as 45 days with positive MRI.

PMID- 21168669
TI  - Effects of cyclooxygenase-2 inhibitor and adenosine triphosphate-sensitive
      potassium channel opener in syngeneic mouse islet transplantation.
AB  - In the initial days after transplantation, islet grafts may be attacked by
      cytokines via cyclooxygenase-2 (COX-2), producing primary nonfunction. In
      addition, chronic overstimulation of beta-cells may impair insulin secretion. To
      enhance the function of transplanted islets, the present study investigated the
      effects of rofecoxib, a COX-2 inhibitor, and NN414 (6-chloro-3-[1
      methylcyclopropyl]amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide), an
      adenosine triphosphate-sensitive potassium channel opener, on islet
      transplantation. Male inbred C57BL/6 mice were used as donors and recipients. One
      hundred fifty islets were isolated via collagenase digestion and density
      gradient, and syngeneically transplanted under the kidney capsule in mice with
      streptozotocin-induced diabetes. Recipients were treated with or without
      rofecoxib, 10 mg/kg/d orally, or with or without NN414, 3 mg/kg/d orally, for 4
      weeks. After transplantation, recipient body weight, blood glucose concentration,
      and intraperitoneal glucose tolerance were measured. The grafted kidney was
      extracted for determination of insulin content at 4 weeks. In the rofecoxib
      treated and NN414-treated groups and both control groups, body weight remained
      stable, and the blood glucose concentration decreased progressively. However, at
      4 weeks after transplantation in the groups treated or not treated with rofecoxib
      or NN414, no significant difference was observed in recipient body weight, blood
      glucose concentration, and glucose tolerance or in insulin content of the graft.
      These data indicate that posttransplantation treatment with rofecoxib or NN414
      has no beneficial effect on transplantation outcome in diabetic mouse recipients
      engrafted with a marginal islet mass.

PMID- 21168670
TI  - Manufacturing of insulin-secreting spheroids with the RIN-5F cell line using a
      shaking culture method.
AB  - BACKGROUND: There have been many efforts to find methods to increase insulin
      production by islets or modified cells. Commercially available established cell
      lines can be a good source of artificial islets. We manufactured sphere-shaped
      cell clusters composed of insulin-secreting cells from the commercially available
      RIN-5F cell line. METHODS: To generate artificial islets with insulin-secretion
      functions, we used the RIN-5F cell line. When cells cultured in RPMI-1640 medium
      containing 10% fetal bovine serum reached near confluency, they were trypsinized
      for suspension culture at high density, using a horizontal shaker. The cells were
      maintained for 5 days under 5% CO(2) with humidification. Next, the media from
      the RIN cell spheroid culture was collected over 5 consecutive days to test for
      insulin secretion. RESULTS: Spheroids of artificial islets exhibited an oval
      shape with an approximate size of 94.13 +/- 20.41 MUm on day 5 during the shaking
      culture. Abnormal outgrowth of spheroids was not observed. Terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells were
      not detected among the overall spheroids, including the core position. Insulin
      secretion, measured by enzyme-linked immunosorbent assay, was well maintained in
      the culture media over 5 days after spheroid formation. CONCLUSION: This result
      suggested that a culture method with shaking can be applied to commercially
      available established cell lines to generate artificial islets, which might be
      used for a bioartificial pancreas.

PMID- 21168671
TI  - Emergency heart transplantation outcome: the Italian experience.
AB  - The National Program for Emergency Heart Transplantation (NP) was implemented in
      2005 is managed at the national level by the Italian National Transplant Center.
      Patients admitted to the NP must be undergoing one of the following treatments:
      short-term Ventricular Assist Device (VAD); complicated medium or long-term VAD;
      complicated Total Artificial Heart; or mechanical ventilation associated with an
      Intra-Aortic Balloon Pump and Continuous Inotrope Therapy (intravenously). The
      aim of this study was to evaluate the NP experience from January 1, 2008, to
      December 31, 2009. We analyzed the number of requests (both fulfilled and not
      fulfilled), the timeliness of organ availability as well as graft and recipient
      survivals at 1 year. During the study period, 108 patients were admitted to the
      NP. The most frequent causes of admission were dilated cardiomyopathies (42.7%)
      and congenital cardiomyopathies (28.7%). Overall, whereas 12 subjects improved 65
      patients underwent heart transplantation (60.2%) and 43 did not undergo surgery
      (39.8%) because of 31 succumbing before a heart became available. The median
      waiting time for heart transplantation was 3 days (range = 0.1-22), compared with
      median waiting time for elective heart transplantation (EHT) of 2.47 years. Graft
      and recipient survivals were 76.0 +/- 1.06 compared with superior graft and
      recipient survivals for EHT during the same period (87.1 +/- 2.0). However,
      implementation of NP has guaranteed heart availability at a short median time,
      thus allowing equitable management of this procedure.

PMID- 21168672
TI  - Cardiac allograft rejection correlates with increased expressions of Toll-like
      receptors 2 and 4 and allograft inflammatory factor 1.
AB  - BACKGROUND: Evidence suggests that injury-induced activation of the recipient's
      innate immune response determines the outcome of allograft transplantation. The
      mechanism responsible for the induction of such innate immune response is not
      clear yet. We hypothesized that in cardiac transplantation settings, the initial
      myocardial ischemia and postischemia graft reperfusion may release allograft
      inflammatory factor (AIF) 1, causing Toll-like receptor (TLR)-mediated activation
      of macrophages and dendritic cells, leading to the production of cytokines and
      the activation of adaptive alloimmunity. Therefore, our goal was to validate the
      presence of these biomarkers in the peripheral blood and biopsy specimens of
      patients presenting allograft rejection. METHODS: We studied 90 peripheral blood
      and 30 endomyocardial biopsy specimens from patients who had undergone cardiac
      transplantation. Specimens were tested by quantitative reverse-transcription
      polymerase chain reaction to determine TLR-2 and -4 and AIF-1 expression levels,
      correlating with clinical rejection grades. The group differences for mRNA
      transcript levels between the rejection grades were determined by 1-way analysis
      of variance. The level of significance was set at P < .05 for comparison between
      the groups. RESULTS: The mean +/- SEM level of TLR-2 mRNA expression was
      increased 1.7-fold in monocytes (P < .05) and 4.2-fold in biopsy samples from
      groups with grade 3A compared with grade 1A or grade 0 rejection (P < .0001). AIF
      1 expression was increased 2.4-fold in monocytes (P < .05) and 4.2-fold in biopsy
      samples comparing grade 3A versus 1A rejections. The TLR-4 mRNA expression was
      also increased in the group with 3A rejections; however, the difference was only
      significant in biopsy specimens (P < .0001). CONCLUSIONS: Our data demonstrated
      that expression profiles of AIF-1 and TLR-2 correlated with biopsy-proven
      allograft rejection in both peripheral blood and local tissue, suggesting their
      potential as diagnostic biomarkers for early detection of allograft rejection.

PMID- 21168673
TI  - Increased adherence after switch from twice daily calcineurin inhibitor based
      treatment to once daily modified released tacrolimus in heart transplantation: a
      pre-experimental study.
AB  - BACKGROUND: Modified release tacrolimus (TAC) is a new, once-daily oral
      formulation of the established immunosuppressive agent TAC. Simplification of
      regimen has been associated with better adherence. This study evaluated patient
      adherence, as well as safety and efficacy among chronic stable heart
      transplantation (HT) patients switched from a conventional twice daily
      calcineurin inhibitor-based regimen (TAC or cyclosporine A [CsA]) to (once daily)
      modified release TAC. METHODS: We switched 54 chronic stable patients (41 males
      and 13 females) from twice daily dosing with conventional TAC or CsA to once
      daily dosing with modified release TAC. Self-reported adherence was assessed at
      baseline and at 4 months after the switch using the Basel Assessment of Adherence
      with Immunosuppressive Medication Scale [BAASIS]), a 4-item validated
      questionnaire including also a Visual Analogue Scale (VAS). Nonadherence was
      defined as any self-reported nonadherence on any item. RESULTS: Modified release
      TAC was discontinued in 4 patients because of diarrhea (n = 1) or
      gastrointestinal discomfort (n = 3) leaving 50 evaluable patients. Overall
      nonadherence at baseline for any of the 4 items was 74% versus 38% after 4 months
      (P = .0001). Thereafter, adherence improved in 28 patients (56.0%), was unchanged
      in 18 (36.0%), and decreased in 4 subjects (8.0%). The VAS score improved from
      82.3% +/- 2.6% to 97.5% +/- 4.8% (P < .0001). No significant changes were
      observed after 4 months regarding hematologic, renal, or liver function
      parameters (all P = NS). CONCLUSIONS: Therapeutic regimens for transplant
      recipients are often complex, contributing to a high incidence of medication
      nonadherence. This study in chronic, stable, heart transplantation patients
      demonstrated a significant improvement in patient adherence after a switch to
      modified release TAC, which was generally well tolerated.

PMID- 21168674
TI  - Proton pump inhibitor co-medication reduces active drug exposure in heart
      transplant recipients receiving mycophenolate mofetil.
AB  - BACKGROUND: Proton pump inhibitors (PPIs) are often prescribed for
      gastrointestinal discomfort after heart transplantation. This study investigated
      the impact of PPI use on mycophenolic acid (MPA) pharmacokinetics in heart
      transplant recipients receiving mycophenolate mofetil (MMF) in combination with a
      calcineurin inhibitor (tacrolimus [TAC]/cyclosporine [CsA]) or mammalian target
      of rapamycin inhibitor (sirolimus/everolimus). METHODS: Abbreviated MPA areas
      under the curve (AUCs; 0, 30, and 120 minutes after morning intake) were obtained
      in 19 patients on a PPI (initial examination) and 1 month after PPI
      discontinuation (follow-up). Mean patient age was 58.2 +/- 8.8 years, and mean
      time after transplantation was 2.3 +/- 4.0 years (range, 0.2-13.0 years).
      RESULTS: At initial examination mean daily MMF dose was 2.2 +/- 0.8 g. MMF dose
      was kept unchanged for the duration of study (P = ns). Mean predose (C0) MPA
      serum concentrations were insignificantly lower with PPI comedication (2.5 +/-
      2.2 mg/L vs 2.8 +/- 1.7 mg/L; P = .15). Dose-adjusted abbreviated MPA AUCs
      (adjusted to morning dose) were significantly lower during PPI therapy (45.2 +/-
      20.3 vs 65.2 +/- 38.8 mg.h/L.g [MMF]; P = .02). CONCLUSIONS: Patients with PPI
      comedication during MMF therapy show significantly lower exposure to mycophenolic
      acid determined by dose-adjusted abbreviated MPA AUCs. Although the clinical
      relevance of this pharmacokinetic interaction was not determined in this study,
      MPA drug monitoring by limited sampling strategies might be helpful during
      changes in antacid comedication in patients on MMF.

PMID- 21168675
TI  - Job resumption status, hindering factors, and interpersonal relationship within
      post-heart transplant 1 to 4 years as perceived by heart transplant recipients in
      Taiwan: a between-method triangulation study.
AB  - INTRODUCTION: This project examined heart transplant (HT) recipients'
      perspectives of (a) the changes in their working competence (WC), status for job
      resumption and related factors at 1- to 2-year, 2- to 3-year, and 3- to 4-year
      stages; and (b) impacts of HT on interpersonal relationships (IPR). METHOD: We
      used a between-method triangulation (including qualitative and quantitative data)
      design. Quantitative data were collected using the Vertical Visual Analogue Scale
      and Taiwan's version of the World Health Organization Health-Related Quality-of
      Life (HRQoL) questionnaire. Six qualitative semistructured questions were further
      applied to explore social and environmental domains. RESULTS: The Fifty subjects
      (86% males and 14% females) had an age range from 20 to 70 years old (mean, 47.68
      years). Their post-HT time ranged from 1 to 4.1 years with 42%, 42%, and 16% at 1
      to 2-, 2- to 3-, or 3- to 4-years post-HT, respectively. Within 6 months, 10% of
      administration or restaurant staff, and police resumed their jobs. At 6 to 12
      months, 8% of administration, quality control, and design and planning staff
      resumed their jobs. At 12 months, 14% of educators, insurance personnel,
      managers, informatics engineers, and ironworkers resumed their jobs. Hindering
      factors to returning to work included (a) physical (ie, lack of energy, second
      heart attack, recurrence of rejection, physical discomforts of dizziness, memory
      lapses/lack of concentration or bone pain from osteoporosis); (b) psychological
      (ie, lack of confidence, worries about discrimination, being different,
      maladaptation); and (c) environmental (inadequate job opportunities due to poor
      socioeconomic conditions). Additionally, 34% reported worse IPR after HT due to
      diet limitations, slower pacing, less contacts with friends, and changes in
      personality. Reflections on both the meaning and value of life caused 10% to
      report better IPR with a better personality and positive mindset. By the end of
      the first postoperative year, the mean score of HRQoL in the preoperative
      extracorporeal membrane oxygenation (ECMO) group was similar to the non
      preoperative ECMO group; the mean scores of WC and physical functions for the
      preoperative ECMO group were even higher than the non-preoperative ECMO group.
      Meanwhile, the mean scores of HRQoL and WC were higher in the Clinical Trail Plan
      (CTP) group than non-CTP groups across the three stages. As such, the use of
      preoperative ECMO and CTP groups are suggested to be both clinically and
      significantly associated with HTs recovery in heath status, positive HRQoL, and
      job resumption in the society. Finally, HRQoL and related domains of physical,
      psychological, social, and environmental health were stable at 12 months post-HT,
      with no significant change between 1- to 2-, 2- to 3-, and 3- to 4-years post-HT.

PMID- 21168676
TI  - Prevalence of chronic kidney disease in orthotopic heart transplant recipients
      and kidney allograft recipients using the new Chronic Kidney Disease Epidemiology
      Collaboration formula.
AB  - Chronic kidney disease (CKD) is an important long-term complication of all forms
      of nonrenal organ transplantation. The aim of this study was to assess the
      prevalence of kidney dysfunction among heart (n = 163) and kidney allograft
      recipients (n = 169) using the new Chronic Kidney Disease Epidemiology
      Collaboration (CKD-EPI) formula, which includes age, gender, and comorbidities.
      The mean serum creatinine values in these populations were 1.58 +/- 0.75 mg/dL
      and 1.36 +/- 0.56 mg/dL, respectively. In heart allograft recipients mean
      estimated glomerular filtration rate (eGFR) by (MDRD) was 57.14 +/- 26.17 mL/min,
      and by CKD-EPI formula was 57.44 +/- 26.76 mL/min whereas in kidney allograft
      recipients it was 63.91 +/- 25.43 mL/min and 65.20 +/- 25.60 mL/min,
      respectively. According to the MDRD formula, stage 2 CKD was noted in 35
      patients; stage 3 CKD in 79 patients, and stage 4 in 23 patients. According to
      the CKD-EPI formula stage 2 CKD was displayed by 35 patients; stage 3 CKD in 78
      patients, and stage 4 in 23 patients. Clinically significant CKD (GFR < 60
      mL/min) was observed in 62% of patients. According to the MDRD normal kidney
      function was present in 22 and according to the CKD-EPI formula in 27 patients.
      According to the MDRD formula stage 2 CKD was found in 59 kidney allograft
      recipients; stage 3 in 58 patients; and stage 4 in 16 patients. According to the
      CKD-EPI formula, stage 2 CKD was noted in 63 patients; stage 3 in 58 patients;
      and stage 4 in 15 patients. Clinically significant CKD was observed in 44% of
      patients. Using MDRD or CKD-EPI normal kidney function was found in 36 and 33
      patient, respectively. CKD prevalence is extremely high among heart and kidney
      transplant recipients. Evaluation of renal function is important to select the
      appropriate strategy to reduce the cardiovascular risk.

PMID- 21168677
TI  - Anemia in heart and kidney allograft recipients: is there a role for hepcidin?
AB  - The production by hepatocytes of hepcidin, a small defensin-like peptide, is
      modulated in response to anemia, hypoxia, or inflammation. We studied hepcidin as
      a marker of iron status (serum iron, ferritin, and soluble receptor of
      transferrin [sTfR], and as a marker of inflammation among 170 prevalent kidney
      transplantation (KT) patients and 168 prevalent orthotopic heart transplant (OHT)
      patients. In addition, we assessed the prevalence of anemia and its relation to
      measurements of hepcidin, sTfR, and high-sensitivity C-reactive protein, using
      commercially available enzyme-linked immunosorbent assay (ELISA) kits. Prevalence
      of anemia was 37% in KT patients and 34% in OHT patients according to the World
      Health Organisation (WHO) definition. Anemic KT patients displayed significantly
      higher values of serum creatinine, hepcidin, hsCRP, ferritin, and proteinuria
      associated with greater use of mTOR and significantly lower CSA therapy. The
      hemoglobin and estimated glomerular filtration rate (eGFR). Upon multiple
      regression analysis eGFR, ferritin, and hsCRP independently predicted hepcidin
      levels, explaining 78% of the variation in hepcidin. Anemic OHT patients showed
      significantly lower GFR, red blood cell (RBC), and hemoglobin values and
      significantly higher creatinine and NT-proBNP content. Upon multiple regression
      analysis the predictors of serum hepcidin were eGFR and ferritin, which explained
      68% of the variation in hepcidin. The prevalence of anemia is relatively high and
      not adequately treated (mainly due to reimbursement regulations) among heart and
      kidney allograft recipients. In conclusion, elevated hepcidin levels in heart and
      kidney transplant recipients suggest subclinical inflammation and impaired kidney
      function.

PMID- 21168678
TI  - Copeptin in relation to New York Heart Association class in heart transplant
      recipients and kidney transplant recipients.
AB  - Copeptin is cosynthesized with vasopressin, also known as antidiuretic hormone.
      It is more stable than vasopressin. Recently copeptin has been studied as a
      diagnostic and prognostic marker for various diseases. Among patients with
      destabilized heart failure, copeptin was an accurate prognostic marker for
      mortality. Chronic heart failure is present in more than one-third of incident
      dialysis patients as well as in kidney allograft recipients. The aim of this
      study was to assess copeptin in orthotopic heart and kidney allograft recipients
      in relation to New York Heart Association (NYHA) class and kidney function. The
      studies were performed on 134 prevalent patients including 103 males and 31
      females after orthotopic heart (OHT) and 80 prevalent kidney allograft recipients
      including 51 males and 29 females. Glomerular filtration rate (GFR) was estimated
      using the simplified MDRD and Chronic Kidney Disease Epidemiology Collaboration
      (CKD-EPI) formulae. We measured complete blood count, urea, serum lipids, fasting
      glucose, creatinine, NT-proBNP using standard methods in the central laboratory
      of the hospital. Plasma copeptin, estimated using a commercially available kit,
      was correlated with kidney function parameters of creatinine, estimated GFR by
      MDRD and CKD-EPI, NT-proBNP and ejection fraction. Copeptin was significantly
      lower among kidney allograft than orthotopic heart recipients: 0.71 +/- 0.13
      ng/mL versus 0.99 +/- 0.36 ng/mL (P < .001). Kidney allograft recipients were
      significantly younger, with shorter times after transplantation, but similar
      serum creatinine and estimated GFR values. Kidney allograft recipients displayed
      lower NYHA classes. Copeptin was higher in chronic kidney disease stage 4 than
      stage 2; similarly in NYHA class III versus I. However, these correlations did
      not achieve statistical significance. There was no effect of gender, diabetes, or
      hypertension on copeptin levels in either group of transplanted patients. Among
      the heart transplant population copeptin is independently associated with kidney
      and heart function, but not in kidney allograft recipients. It may also predict
      outcomes of orthotopic heart transplant patients.

PMID- 21168679
TI  - Blood pressure control in orthotopic heart transplant and kidney allograft
      recipients is far from satisfactory.
AB  - Hypertension is widely accepted as a risk factor for coronary artery disease,
      heart failure, stroke, or chronic kidney disease. According to ESH/ESC and JNC
      guidelines, the target blood pressure should be low 140/90 mm Hg in the general
      population, and 130/80 mm Hg among patients with chronic kidney disease or
      diabetes. The aim of this study was to assess the prevalence of achieved target
      blood pressure among 164 prevalent heart transplant recipients as well as 172
      prevalent, kidney transplant, 100 hemodialyzed, and 50 peritoneally dialyzed
      patients on renal replacement therapy. We assessed kidney function in
      transplanted patients using the simplified MDRD formula. In the heart transplant
      (OHT) population, 10% had diabetes and 65% chronic kidney disease; in the kidney
      transplant population 18% had diabetes. Hypertension was treated in 70% of OHT,
      92% of kidney 90% of hemodialyzed and 70% of peritoneally dialyzed patients. In
      the OHT population, only 43% of subjects achieved the target blood pressure,
      while 42% among kidney transplant, 50% of hemodialzyed, and only 20% of
      peritoneally dialyzed patients did so. Hypertensive OHT as well as kidney
      transplant subjects were older, displayed higher serum creatinine values and
      lower estimated glomerular filtration rates. Hypertensive patients after OHT were
      treated with ACE inhibitors (50%), calcium channel blockers (55%), diuretics
      (34%), beta-blockers (34%), and/or spironolactone (5%). Among hypertensive kidney
      allograft recipients, the most commonly used drugs were calcium channel blockers
      (80%), beta-blockers (60%), diuretics (55%) ACE inhibitors (40%), and alpha
      blockers (12%). The kidney transplant population required three and more
      hypotensives in 63% of cases. Despite polytherapy optimal blood pressure control
      was not achieved in the majority of patients. OHT and kidney graft recipients
      displayed a high prevalence of hypertension, which should be treated adequately.
      More efforts must be dedicated to optimize blood pressure control, particularly
      in the presence of other comorbidities.

PMID- 21168680
TI  - Association between panel reactive antibodies and acute small bowel rejection:
      analysis of a series of 324 intestinal transplants.
AB  - INTRODUCTION: Panel reactive antibodies (PRA) to class I and II HLA molecules
      have been associated with acute kidney graft rejection, but their role in small
      bowel transplantation has not been characterized. METHODS: Since 1994, 324 SBT,
      alone or as multivisceral transplantation (MVT), have been performed in 286
      patients. Routine and surveillance biopsies were performed to rule out or confirm
      acute rejection (AR), and PRA quantification was performed at varying intervals.
      We obtained data from 110 patients and 651 PRA measurements. While AR grade (mild
      to severe, grades 1-3) was determined by histopathological analysis, the status
      of no AR was determined also by clinical data. When biopsy samples or PRA
      measurements were frequent around an AR episode within periods of 7 days, the
      highest value was used. RESULTS: A comparison could be made between 259 instances
      in which there was a PRA measurement and simultaneous rejection evaluation.
      Positive PRA showed association with AR (P < 0.001). The positive and negative
      predictive values were 44% and 79%, respectively. No correlation was found in the
      severity of rejection. CONCLUSION: The presence of increased levels of PRA is a
      risk factor of rejection in small bowel transplantation. Alloantibody-mediated
      injury to the graft contributes frequently to acute rejection of small bowel, and
      it is associated with cell-mediated immunity in variable proportion.

PMID- 21168681
TI  - Outstanding survival and regeneration process by the use of intelligent acellular
      dermal matrices and mesenchymal stem cells in a burn pig model.
AB  - A pig model with a deep large burn was used to study the regeneration process
      induced by mesenchymal stem cells (MSCs) and acellular pig dermal matrices, made
      intelligent by the combination with biodegradable nanofibers loaded with growth
      factors (granulocyte-macrophage colony-stimulating factor and epidermal growth
      factor) and coated with the anti-CD44 monoclonal antibody (intelligent acellular
      dermal matrices, IADMs). These IADMs are specially designed to integrate in the
      wound bed as new biological scaffolds as well as to specifically recruit and
      attach circulating and/or externally applied MSCs through the anti-CD44 antibody
      while delivering precise amounts of growth factors. In this way, the reparative
      process as well as the aesthetic and functional results were enhanced in our burn
      model. The animal survived, the wound was completely closed, and total
      regeneration of the skin was obtained without much scarring. Surprisingly, hair
      follicles and other skin appendages developed despite the severity and deepness
      of the burn. Even burned muscles and ribs seemed to have undergone a regenerative
      process by the end of the study. Based on these findings, we have proposed the
      use of IADMs and autologous, allogeneic or xenogeneic MSCs, as a new paradigm for
      the future treatment of large burns and probably other dermatological and
      cosmetic human conditions.

PMID- 21168682
TI  - The role of liver stromal cells in dendritic cells development in mice.
AB  - The inherent tolerogenicity of liver allografts may be due to tolerogenic
      dendritic cells (DC) therein. It is not clear whether the unique antigen
      presenting function of liver DC is intrinsic or whether it is altered by
      microenvironmental factors in the liver. In the present study, we investigated
      the effect of hepatic stellate cells (HSC) on the development and function of DC
      propagated from bone marrow. DC exposed to HSC or HSC supernates expressed low
      CD11c, CD86, and major histocompatibility complex class II and elicited inferior
      allostimulatory function compared with conventional DC. These results suggested
      that soluble factor(s) secreted from HSC influence DC development.

PMID- 21168683
TI  - Lymphangiogenesis associated with acute cellular rejection in rat liver
      transplantation.
AB  - Lymphangiogenesis may be important for the cellular immune response in liver
      transplantation. In the present study, we examined lymphangiogenesis in liver
      allografts displaying acute cellular rejection (ACR), or long-term acceptance, or
      severe ACR plus antibody-mediated rejection (AMR). ACR and subsequent long-term
      graft acceptance developed in liver transplantations from DA to PVG rats without
      immunosuppression (mean survival time more than 90 days). Severe ACR and AMR
      developed in liver transplantations from DA to Lewis rats without
      immunosuppression (mean survival = 11 days). Normal DA donor livers before
      transplantation showed a small number of lymphatic vessels around portal veins.
      DA liver grafts in PVG showed ACR with lymphangiogenesis in portal areas and
      portal-portal bridging areas with cellular infiltration. Newly formed lymphatic
      vessels in ACR were characterized by proliferating endothelial cells with
      expression of the homeobox transcription factor PROX-1 and surrounded by
      discontinuous basement membranes. Thereafter, the infiltrates spontaneously
      disappeared, and the grafts survived more than 90 days. During the resolution of
      the cellular infiltration, expanded lymphatic vessels were packed with many
      lymphocytes. Thereafter, the number of lymphatic vessels decreased. In contrast,
      severe ACR and AMR in DA-to-Lewis transplantations showed lymphatic vessels
      disappeared with edema in the portal areas at day 11. In conclusion,
      lymphangiogenesis occurred during ACR. It may be involved in the resolution of
      ACR and reduction of inflammation. In severe ACR and AMR, lymphatic vessels were
      destroyed, which may be involved in persistent severe inflammation.

PMID- 21168684
TI  - Impact of graft type on remnant liver regeneration: right hepatectomy versus
      extended right hepatectomy.
AB  - Right hepatectomy with the middle hepatic vein (MHV) affects venous return and
      function of the remaining liver. We compared the remnant liver volume in the
      donors of resection with or without the MHV on the remnant liver volume
      regeneration. Living donors who had undergone right hepatectomy without MHV (RH
      group; n = 36) and those with MHV (ERH group; n = 19) were reviewed. Volume
      regeneration of segments I-III, segment IV, and total remnant liver volume was
      assessed at postoperative day (POD) 7 and 30 using a computed tomography-based
      volumetry program. According to the measured volume data, we calculated the liver
      remnant volume and the rate of liver remnant volume increase. The regeneration
      rate of segment IV was significantly low in the ERH group compared with that in
      the RH group at POD 7 and POD 30 (160% vs 141%; P = .018 and 189% vs 154%; P =
      .007). In contrast, the regeneration rate of the total remnant liver volume was
      not significantly different between the 2 groups (173% vs 175%; P = .758 and 199%
      vs 198%; P = .880). In conclusion, extended right hepatectomy can be safely
      performed with careful preoperative evaluation without significant impairment of
      remnant liver regeneration.

PMID- 21168685
TI  - An unusual presentation of a Page kidney 24 days after transplantation: case
      report.
AB  - The Page kidney phenomenon is a well recognized entity where an extrinsically
      compressed kidney results in hypertension and loss of function. This compression
      is usually caused by a subcapsular hematoma secondary to blunt abdominal trauma
      or an invasive procedure such as a renal biopsy. We describe an unusual case
      involving the spontaneous development of a Page kidney 24 days after renal
      transplantation without any history of preceding trauma. The subcapsular hematoma
      was detected by a computerized tomographic scan performed as part of the work-up
      for acute allograft dysfunction. Prompt recognition and early intervention are
      essential if renal function is to be restored before irreversible damage occurs.

PMID- 21168686
TI  - Challenges in the diagnosis of 2009 H1N1 in a lung transplant patient and the
      long-term implications for prevention and treatment: a case report.
AB  - Although respiratory viral infections have been associated with acute rejection
      and bronchiolitis obliterans syndrome, the long-term impact of the novel pandemic
      influenza A (2009 H1N1) virus on lung transplant patients has not been defined.
      We describe the diagnostic challenges and long-term consequences of 2009 H1N1
      infection in a lung transplant patient, discuss the potential implications for
      prevention and treatment, and conclude that even timely antiviral therapy may be
      insufficient to prevent long-term morbidity.

PMID- 21168687
TI  - Attitude of the Omani population toward organ transplantation.
AB  - Transplantation from deceased donors is still scarce in Oman, mainly due to
      family refusal. We conducted a survey to learn the attitudes of the Omani
      population regarding transplantation. SUBJECTS AND METHODS: Among 500 individuals
      who were distributed, a questionnaire 304 responded including 247 (81%) Omani and
      57 (19%) foreign residents. There were 213 (70%) male respondents of the 304
      subjects, 256 individuals (84%) were between 18 and 50 years of age, and 270
      (89%) had at least a high school education. RESULTS: Thirty-eight percent and 32%
      of Omani individuals had a family member or a friend with kidney disease or a
      renal transplantation, respectively. Only 42% of respondents knew that renal
      transplantation is performed in Oman. It was encouraging to note that 65% of
      Omanis knew that commercial transplantations are against Islamic and
      international standards. Sixty-four percent of the respondents stated that they
      would donate a kidney to a relative with renal failure. Nevertheless, only 49%
      knew that donation after death is permitted by Islam; 42% respondents would
      accept a kidney from a deceased person. Only 35% would donate a kidney or an
      organ after death. We concluded that the awareness of the Omani people toward
      donation after death is low, with a great need for public education and awareness
      programs, particularly for high school and university students.

PMID- 21168688
TI  - Short- and long-term outcomes of living donors in Tunisia: a retrospective study.
AB  - Despite initiatives to increase cadaveric donation, there is still a shortfall in
      donor organs. Kidneys from living donors now makes a significant contribution to
      increasing the number of organs available for transplantation in Tunisia. We
      performed a retrospective study of 405 kidney transplantations, including 321
      (79.3%) from living donors performed from June 1986 to December 2007. We obtained
      information on only 162 (50.4%), namely, 64 men (39.5%) and 98 women (60.5%),
      whose mean age at the time of donation was 42.3 +/- 12.2 years. Twelve (8.22%)
      perioperative complications occurred: wound infections (n = 4), pneumothorax (n =
      4), phlebitis (n = 1), hematomas (n = 2), and urinary infection (n = 1). The mean
      follow-up period was 117.4 +/- 74.4 months. Hypertension occurred in 42 donors
      (25.9%) with mean values of 134 +/- 20 for systolic and 79 +/- 10 for diastolic
      blood pressure. Twelve donors (7.4%) developed proteinuria (mean proteinuria,
      0.08 +/- 1.25 g/d). Renal insufficiency was found in 28 donors (19.44%), 2 of
      whom developed chronic renal failure requiring dialysis at intervals of 36 and 84
      months. In both cases, we diagnosed a familial form of focal segmental
      glomerulosclerosis. Two donors (1.2%) died within 10 years after kidney donation
      due to senility. The relatively favorable outcomes suggest that living-donor
      kidney transplantation is an acceptable approach, in view of the superior results
      it yields in recipients. However, efforts to increase the number of cadaveric
      donors in Tunisia should be made. It is also important to develop a registry of
      long-term kidney function after kidney donation.

PMID- 21168689
TI  - (AT) repeat in the 3' untranslated region of the CTLA-4 gene and susceptibility
      to acute allograft rejection in Tunisian renal transplantation.
AB  - Allograft rejection is an immune response relying on the proliferation and the
      differentiation of T cells. CTLA-4 is a co-stimulatory molecule, expressed on
      activated T lymphocytes, which has been shown to play a crucial role in the down
      regulation of T-cell activation. Herein, we have examined the impart of a genetic
      marker in the CTLA-4 gene on renal transplant outcomes. A cohort of 144 renal
      recipients and 100 healthy subjects were genotyped by the fragments analysis
      method using an automated sequencer. Patients were classified into two groups:
      Group I included 31 HLA-identical haplotype allograft recipients and Group II,
      113 showing one or more HLA haplotype mismatches. Forty patients (27.78%)
      developed at least one acute rejection episode (ARE): 9 in Group I and 31 in
      Group II. Before transplantation, 20 patients were lymphocytotoxic antibodies
      (LCT) positive: 4 Group I, 2 of whom developed an ARE, and sixty in Group II,
      including 8 with an ARE. The occurrence of an ARE was associated with the
      presence of LCT before transplantation among the entire cohort of patients (P =
      .032) and among Group II (P = .037). The allelic frequencies of (AT)n
      polymorphism did not reveal significant differences between patients and
      controls. The most prevalent alleles were the 88 bp (51% in controls and 44.44%
      in patients) and the 106 bp (8% and 10.76%, respectively). We noticed an increase
      of the 120 bp allele frequency among patients who had undergone an ARE compared
      with those who did not display this complication (8.75% vs 3.85%). Likewise,
      among LCT-negative Group I, recipients the incidence of the 120 bp allele was
      higher in ARE than non-ARE patients. Although the differences were not
      statistically significant, we propose that the 120 bp allele of the CTLA-4 gene
      (AT)n microsatellite a predisposes to acute rejection episodes in renal
      transplantation.

PMID- 21168690
TI  - MICA gene polymorphism in kidney allografts and possible impact of functionally
      relevant variants.
AB  - It is likely that the polymorphic MICA (MHC class I related chain A) molecules on
      graft endothelial cells (ECs) may be a target for specific antibodies and T cells
      directed against solid organ grafts. Although there is evidence for a role of
      MICA in vascular and transplant biology, genotyping is not performed routinely,
      and thus there are few correlations between polymorphism and endothelial
      phenotype. The present study examined the frequency of the various alleles for
      the nonclassical MHCI MICA gene among a cohort of kidney transplant donors,
      particularly MICA genetic variants (MICA A5.1 and MICA-129) that may affect MICA
      expression and function on graft EC. Genotyping was performed on genomic DNA
      derived from primary cultures of EC established from transplant donors at the
      time of transplantation. Herein we have reported that among 106 alleles analyzed,
      28/69 MICA alleles were distributed among 7 major variants (*00804, *00801, *004,
      *00201, *00901*, *011, *010), representing 70% of the donors. MICA*008 the most
      abundant allele (31.1%) was associated with the MICA A5.1 mutation. The majority
      of donors (52.8%) had at least one MICA A5.l allele, with 13.2% homozygous for
      this mutation. The MICA-129 val/val genotype, which encodes a low-affinity
      ligand, was predominant (49%), while the MICA-129 met/met, corresponding to a
      high-affinity ligand, was observed in 11.3% of the transplants. Our findings
      highlighted the MICA gene polymorphism that produces functional diversity in
      transplant recipients with variable interactions between MICA and its receptor
      NKG2D.

PMID- 21168691
TI  - Complicated lymphoceles after kidney transplantation.
AB  - Lymphocele is a common surgical complication after renal transplantation. The
      incidence of lymphocele ranges from 0.6% to 18%. The aim of this study was to
      determine incidence, risk factors and prognosis of complicated lymphocele in the
      era of modern immunosuppression. We retrospectively reviewed 311 renal
      transplants from January 2003 to September 2008, we excluding patients who
      received sirolimus or underwent multiorgan transplantations. A complicated
      lymphocele was defined by the requirement for a surgical procedure for cure. Of
      the 311 transplant recipients, we included 269 in the study with 49 (18.9%)
      presenting a complicated lymphocele after transplantation. Cold ischemia time,
      waiting time on dialysis, gender, donor source, induction therapy (thymoglobulin
      vs basiliximab), and dialysis modality were similar between the 2 groups.
      Mycophenolate mofetil (MMF) doses were higher among the lymphocele than the
      nonlymphocele group (2.7 +/- 0.54 g/d vs 2.36 +/- 0.68 g/d; P < .05). However,
      the areas under the concentration-time curves of mycophenolic acid were not
      significantly different between the 2 groups (43.7 +/- 15.3 h.mg/L vs 48 +/- 21
      h.mg/L; P = .33). However, a multivariate analysis showed complicated lymphocele
      to be associated with greater MMF doses (odds ratio [OR] 2.75; P < .01), warm
      ischemia time (OR 1.035; P < .05), and recipient age (OR 1.04; P < .05). In
      conclusion, we identified high MMF doses as an independent risk factor for
      lymphocele formation after renal transplantation.

PMID- 21168692
TI  - A novel surgical technique for management of vesicoureteral reflux following
      kidney transplantation: prospective study of 12 cases.
AB  - The incidence of vesicoureteral reflux (VUR) varies between 10% and 80% of
      transplanted kidneys. In cases of failure of endoscopic treatment or recurrent
      urinary tract infections, surgical correction is proposed by ureteral
      reimplantation or pyeloureteral anastomosis using the native ureter. The aim of
      this study was to assess the results of a technique that increases the submucosal
      length of the ureter without a ureterovesical reimplantation. We treated 12
      patients with VUR in the transplanted kidney by open surgery. Retrograde
      cystography showed resolution of reflux in all the patients. Our technique has
      the advantage of avoiding ureteral dissection thereby avoiding its
      devascularization and no invasion of the bladder mucosa.

PMID- 21168693
TI  - Sublingual tacrolimus as an alternative to intravenous route in patients with
      thoracic transplant: a retrospective study.
AB  - Tacrolimus (TRL) is an immunosuppressive drug characterized by a narrow
      therapeutic index, low bioavailability, and pharmacokinetic variability.
      Intravenous (i.v.) TRL may be needed whenever the oral route is unavailable. The
      small amount of infusion formulation (5 mg/mL) results in a large dilution and
      need for careful technical management of the infusion. This study addressed the
      feasibility to provide sublingual (SL) as an alternative to i.v.. TRL for
      transplanted patients. In a substudy, we performed a retrospective analysis of 17
      lung and heart transplant patients using SL TRL. It included therapeutic drug
      monitoring and 4 area under curve (AUC) measurements. Patients received SL TRL on
      a dose-to-dose basis from the oral formulation. The mean age of the subjects (14
      male, 3 female) was 35.3 +/- 15.6 years; 146 trough (C(0)) samples were collected
      during the SL period (15.8 +/- 20.6 days) showing a conformity level of 90.4%.
      Mean dose, C(0), and AUC of SL tacrolimus were 0.116 +/- 0.096 mg/kg, 12.9 +/- 5
      ng/mL, and 230 +/- 74 ng.h/mL, respectively, with an average 1 hour time to peak
      concentration. Acute rejection episodes, renal toxicity, and drug interactions
      were not observed. This study supported the convenience of short-term SL TRL
      administration, even in unconscious patients. Further investigations are needed
      to validate the dose range of the SL route.

PMID- 21168694
TI  - Combined pancreatic islets-lung transplantation in cystic fibrosis-related
      diabetes: case reports.
AB  - We report two cases of percutaneous portal embolization of pancreatic islets
      performed after double lung transplantation in cystic fibrosis (CF) patients
      using the pancreas of the same donor. CASE 1: A 19-year-old man with CF had
      insulin-dependent diabetes, which was poorly controlled despite an external
      insulin pump (96 IU/d): HbA(1c) = 9.8% and 1 to 3 hypoglycemic events per day. On
      October 29, 2007, he received a double lung graft because of chronic respiratory
      failure. For days after lung transplantation, 149,000 cultured IEQ (Islet
      EQuivalent) were injected by percutaneous intraportal infusion under local
      anesthesia. Immunosuppression consisted of steroids, cyclosporine, and
      azathioprine. Two years later, the forced expiratory volume (FEV) was 83%; C
      peptide level reached 1.4 MUg/L, and the diabetes was satisfactorily controlled
      with an HbA(1c) of 7.5% and a decrease in insulin requirements to 30 U/d in the
      absence of hypoglycemic events. CASE 2: On July 10, 2006, a 32-year-old man with
      CF-related diabetes received a double lung graft because of chronic respiratory
      failure. Under multiple insulin injections, the HbA(1c) was 9.6% with numerous
      hypoglycemic events. On March 11, 2008, he again received a double lung graft
      because of persistent humoral rejection. Despite severe bleeding during the
      postoperative course, 234,000 IEQ were injected via the portal vein one week
      after lung transplantation. Immunosuppression consisted of steroids, tacrolimus,
      and mycophenolate mofetil. Eighteen months after the combined graft, the FEV was
      52%; the plasma C-peptide reached 0.79 MUg/L, the HbA(1c), 6% and the insulin
      requirements decreased to 55 U/d in the absence of hypoglycemic events.
      CONCLUSION: Combined lung-islet transplantation for patients with CF-related
      diabetes improved pulmonary and metabolic function.

PMID- 21168695
TI  - Cyclosporine inhibits profibrotic effects of interleukin-4 and transforming
      growth factor beta on human intrahepatic fibroblasts cultured in vitro.
AB  - BACKGROUND: Hepatic fibrosis, an outcome of chronic liver diseases, is
      characterized by an accumulation of collagen, which is produced by activated
      human intrahepatic fibroblasts (HIF). Transforming growth factor (TGF) beta is an
      important inducer of fibrogenesis, in collaboration with other cytokines, such as
      interleukin (IL) 4. IL-4 is overexpressed in severe recurrent hepatitis C after
      liver transplantation, exerting profibrotic effects. In contrast, cyclosporine
      (CsA) had been shown to decrease fibroblast activation and collagen production.
      We therefore investigated the effects of CsA on TGF-beta and IL-4 profibrotic
      activities on HIF in vitro. METHODS: Isolated HIF were cultured without or with
      human TGF-beta, human IL-4, CsA, or combined TGF- beta+CsA or IL-4+CsA. We
      performed real-time polymerase chain reaction for collagen types I, III, and IV
      and alpha-SMA, a marker of fibroblast activation we also measured total collagen
      in supernates. TGF-beta and IL-4 increased the expressions of alpha smooth muscle
      action (SMA) collagen I, III, and IV mRNAs (P < .05 vs untreated cells) as well
      as the overall collagen level in the supernates (P < .01). CsA decreased the
      expression of mRNAs encoding alpha-SMA and collagens (P < .01). Expressions of
      alpha-SMA and collagens I, III, and IV mRNAs were significantly lower under
      combined treatments (TGF-beta vs TGF-beta+CsA [P < .01] and IL-4 vs IL-4+CsA [P <
      .01]). Collagen level was decreased by combined treatments (TGF-beta vs TGF
      beta+CsA [P < .05] and IL-4 vs IL-4+CsA [P = .05]). CONCLUSION: CsA inhibited the
      profibrotic effects of TGF-beta and IL-4 by decreasing the activation and
      production of collagen by HIF. CsA may decrease fibroblast activation and
      collagen accumulation, exerting beneficial effects on fibrosis progression,
      particularly among patients with recurrent hepatitis C.

PMID- 21168696
TI  - Injection of donor-derived splenic dendritic cells plus a nondepleting anti-CD4
      monoclonal antibody to prolong primary skin graft survival indefinitely and
      abrogate the production of donor-specific antibodies in the Fischer-to-Lewis rat
      combination.
AB  - We have previously shown that injection of donor-derived Fischer rat OX62+
      dendritic cells plus an anti-CD4 monoclonal antibody generates donor-specific
      CD4+CD25+FoxP3+ regulatory T cells in Lewis rats spleens. The regulatory T cells
      indefinitely prolonged the survival of skin graft from Fischer rat and abrogated
      the antidonor antibody response. We have now shown that an injection of 2 * 10(6)
      donor-derived OX62+ dendritic cells plus 2 mg nondepleting anti-CD4 monoclonal
      antibody (W3/25) at 28 days before grafting induced indefinite skin graft
      survival in this combination; whereas an injection on day -1 prolonged it only to
      50 days. This effect is donor specific. In both cases, we suppressed the
      antidonor antibody response. It is likely that the efficacy of this protocol is,
      at least in part, dependent on induction of donor-specific regulatory T cells, as
      suggested by previous data. The 28 days necessary to obtain tolerance of
      allogenic skin grafts may be due to the time required for the host to induce
      proliferation of donor-specific regulatory T cells.

PMID- 21168697
TI  - Eculizumab: safety and efficacy after 17 months of treatment in a renal
      transplant patient with recurrent atypical hemolytic-uremic syndrome: case
      report.
AB  - In a recent study, eculizumab, a humanized monoclonal antibody which targets
      complement factor C5, appeared to resolve hemolysis and thrombocytopenia leading
      to recovery of renal function in a transplant patient during an episode of an
      atypical hemolytic uremic syndrome. We report the efficacy of eculizumab in a
      patient who presented with a recurrence of atypical hemolytic syndrome at 3 years
      after renal transplantation. After 17 months of eculizumab treatment, and without
      concomitant plasma therapy, renal function was maintained, the need for blood
      transfusions reduced, and acute thrombotic microangiopathy and hemolysis
      controlled. These data suggested that eculizumab should be considered to be a
      permanent treatment for this patient.

PMID- 21168698
TI  - Epstein-Barr virus-associated hepatic leiomyosarcoma after renal transplantation:
      case report.
AB  - The incidence of neoplastic complications after solid organ transplantation is
      increasing tremendously probably as the consequence of long term
      immunosuppression. Beside usual risk factors, the oncogenic role of some viruses
      like Epstein-Barr virus is well established. We report a case of a primitive EBV
      induced liver leiomyosarcoma after renal transplantation.

PMID- 21168699
TI  - Nocardia carnea infection in a kidney transplant recipient.
AB  - We report an unusual case of Nocardia carnea brain and lung abscesses in a 54
      year-old kidney transplant recipient. Our case was confirmed by molecular
      detection despite negative cultures. The patient recovered using prolonged
      cotrimoxazole treatment.

PMID- 21168700
TI  - Organ donation in Belgium 2009: 20% of donation after cardiocirculatory death.

PMID- 21168701
TI  - Contribution of donors after cardiac death to the deceased donor pool: 2002 to
      2009 University of Liege experience.
AB  - OBJECTIVE: In this study, we have evaluated the organ procurement and
      transplantation activity from donors after cardiac death (DCD) at our institution
      over an 8-year period. Our aim was to determine whether this program influenced
      transplantation programs, or donation after brain death (DBD) activity. METHODS:
      We prospectively collected our procurement and transplantation statistics in a
      database for retrospective review. RESULTS: We observed an increasing trend in
      potential and actual DCD number. The mean conversion rate turning potential into
      effective donors was 58.1%. DCD accounted for 16.6% of the deceased donor (DD)
      pool over 8 years. The mean age for effective DCD donors was 53.9 years (range, 3
      79). Among the effective donors, 63.3% (n = 31) came from the transplant center
      and 36.7% (n = 18) were referred from collaborative hospitals. All donors were
      Maastricht III category. The number of kidney and liver transplants using DCD
      sources tended to increase. DCD kidney transplants represented 10.8% of the DD
      kidney pool and DCD liver transplants made up 13.9% of the DD liver pool over 8
      years. The DBD program activity increased in the same time period. In 2009, 17
      DCD and 33 DBD procurements were performed in a region with a little >1 million
      inhabitants. CONCLUSION: The establishment of a DCD program in our institution
      enlarged the donor pool and did not compromise the development of the DBD
      program. In our experience, DCD are a valuable source for abdominal organ
      transplantation.

PMID- 21168702
TI  - Ethylene oxide allergy in patients on hemodialysis waiting for kidney
      transplantation: logistical nightmare or challenge? A case report.
AB  - Ethylene oxide (EO) is widely used as a sterilization gas for heat-sensitive
      devices. In EO-sensitized patients, this type of sterilization can cause rare but
      major allergic reactions such as hives, rash, asthma, or anaphylactic shock.
      Hemodialysis patients in particular are at risk of developing hypersensitivity to
      EO. In these patients, surgical interventions should be planned far in advance
      allowing a thorough EO-free preparation of all equipment needed for the surgery
      as well as for the pre-, peri-, and postoperative care. In contrast to elective
      surgery, kidney transplantation with allografts from deceased donors cannot be
      planned; exact timing is unpredictable. Furthermore, transplantation may take
      place years after patients have been put on the waiting list. Listing of patients
      sensitive for EO is therefore a logistical and medical challenge for all health
      care professionals involved in the patient's care (eg, surgeons, nephrologists,
      anesthetists, nurses, pharmacists, and sterilization specialists). This case
      report describes a patient with chronic kidney disease stage V who developed EO
      allergy during hemodialysis while waiting for a kidney transplantation. Diagnosis
      was made based on clinical signs and confirmed biochemically (including a
      positive radioallergosorbent test). Because the only treatment is avoidance of
      contact with EO-sterilized materials, a strict EO-free protocol was developed to
      allow an uneventful transplantation thereafter. Subsequently, 4 newly diagnosed
      EO-sensitive patients on the active kidney transplantation waiting list were
      diagnosed, and 1 of these patients has been transplanted successfully. EO allergy
      in patients on the waiting list for kidney transplantation is a unique
      challenging situation which, to the best of our knowledge, has not been reported
      yet for kidney transplantation. This report further highlights the logistical
      preparation of a renal transplantation, including anesthesiologic, surgical, and
      postoperative care.

PMID- 21168703
TI  - Posttransplantation diabetes mellitus: a long-term retrospective cohort study.
AB  - BACKGROUND: Posttransplantation diabetes mellitus (PTDM) is a serious
      complication of transplantation which is caused by immunosuppressive drugs and
      adversely affects the survival of the transplant recipient and the long-term
      survival of the graft. In this study, we assessed the incidence of PTDM and the
      factors associated with its development during long-term follow-up of renal
      transplant recipients. We also investigated the influence of PTDM on the
      cardiovascular risk (CVR) profile. METHODS: We retrospectively reviewed the
      records of the patients who underwent renal transplantation at our center between
      1986 and January 2007. Diabetes was diagnosed according to American Diabetes
      Association criteria. The CVR factors were analyzed at the time of
      transplantation as well as at 1 and 3 years follow-up. RESULTS: We included 136
      nondiabetic transplant recipients. The PTDM incidences at 1, 3, 5, and 10 years
      were 9%, 12%, 13%, and 16.4%, respectively. The cumulative incidence during
      follow-up was 17.6%. On both univariate and multivariate analyses body mass index
      (BMI) was significantly associated with PTDM. Patients with BMI 25 = 30 kg/m(2)
      had an odds ratio [OR] of 3.53 (95% confidential interval [CI] 1.26-9.90; P =
      .017) and those with BMI >30 kg/m(2) had an OR of 4.58 (95% CI 1.4-14.01; P =
      .012). There were no significant differences in gender distribution, age,
      pretransplant dialysis period, acute rejection rate, or immunosuppressive
      regimens between patients with (n = 24) versus without (n = 112) PTDM.
      CONCLUSION: The risk of PTDM increased continuously with time after
      transplantation. BMI was an independent predictor of PTDM. Among all of the risk
      factors for PTDM, obesity is the only modifiable risk factor before
      transplantation. PTDM was associated with a worse traditional CVR profile; a
      better control of CVR factors should be performed to prevent long-term morbidity
      and mortality in this population.

PMID- 21168704
TI  - Acute femoral neuropathy: a rare complication after renal transplantation.
AB  - OBJECTIVE: Femoral neuropathy is a rare but disabling complication following
      renal transplantation and pelvic surgery in general. In a retrospective review,
      we analyzed the incidence, clinical presentation, and outcome of this
      complication after renal transplantation in our center. In addition, we conducted
      a literature search on this complication. MATERIALS AND METHODS: Five cases of
      isolated femoral neuropathy after renal transplantation were encountered at our
      center, out of 3,448 renal transplantations performed over a 47-year period.
      RESULTS: All of these patients presented with a weakness of hip flexion
      (iliopsoas muscle) and knee extension (quadriceps muscle) starting immediately
      after surgery. Atrophy of the quadriceps became apparent in severe and prolonged
      cases. In addition, numbness and paresthesia located in the anteromedial part of
      the thigh were present in 3 patients. CONCLUSION: Isolated neuropathy of the
      femoral nerve is a rare but disabling complication after renal transplantation.
      The etiology of isolated femoral neuropathy often results from direct compression
      of the femoral nerve or from indirect compression on the psoas muscle by
      application of self-retaining retractors placed during pelvic surgery. Other
      factors that can play a role in the pathogenesis are related to direct ischemia
      of the nerve by clamping of the iliac artery, thus interrupting the pelvic blood
      supply to the femoral nerve during the vascular anastomosis or vessel dissection,
      or by postoperative hematoma in the retroperitoneum or psoas muscle. Meticulous
      surgery and careful positioning of the self-retaining retractors during surgery
      are pivotal to avoid this complication which transplant surgeons should be aware
      of.

PMID- 21168705
TI  - Renal transplantation from living related donors: a single center experience in
      Viet Nam.
AB  - INTRODUCTION: End-stage renal disease is a major public health problem in Viet
      Nam. A cooperative project between the University of Liege, Belgium, and the
      University of Medicine Pham Ngoc Thach, Ho Chi Minh City, Viet Nam, has permitted
      the establishment of an autonomous program of renal transplantation from living
      related donors at the Peoples' Hospital No 115. The aim of this paper was to
      report the primary results of the project and to draw conclusions for the future.
      PATIENTS AND METHODS: From January 2004 to July 2008, we performed 33 living
      related renal transplantations. Mean ages of donors and recipients were 31.8 +/-
      9.5 and 41.6 +/- 13.5 years, respectively. Laparoscopic nephrectomy was performed
      in 6 donors. The immunosuppressive regimen consisted of three drugs associated
      with induction therapy using anti-interleukin-2 receptor monoclonal antibody.
      RESULTS: The 33 donors are in good health at follow-up. Four developed major
      intra- or postoperative hemorrhage necessitating transfusion, with a surgical re
      exploration in 1 donor. Wound infection occurred in 2 donors. Posttransplant
      recipient and graft survivals at 1 versus 3 years were 82% and 73% versus 82% and
      65%, respectively. Eight recipients presented 13 biopsy-proven acute rejection
      episodes that were reversible in 7, but 1 patient lost his graft due to an
      irreversible rejection. Two recipients developed cancer. CONCLUSIONS: These
      initial results have encouraged us to continue the program of renal
      transplantation from living-related donors. However, they also pointed out the
      need to develop other donor sources.

PMID- 21168706
TI  - The multicenter Belgian survey on liver transplantation for hepatocellular
      failure after bariatric surgery.
AB  - The prevalence of obesity has grown dramatically over the last decades, with
      nonalcoholic steatohepatitis increasingly observed. Therapeutic options for
      morbid obesity include bariatric surgery. Fatal liver failure (LF) has been
      recorded after jejunoileal bypass (JIB) but is controversial after
      biliopancreatic diversion (BPD, Scopinaro operation). We performed a survey on
      the frequency of liver transplantation (LT) after bariatric surgery in Belgium.
      An enquiry was sent to all Belgian liver transplant centers to investigate the
      occurrence of subacute and chronic LF after bariatric surgery. After weight
      reduction surgery, 10 patients in 3 Belgian transplant centers were listed for LT
      due to severe hepatocellular failure. Nine of them had undergone a Scopinaro
      operation and 1 a jejunoileal bypass. The median time to develop LF was 5 years.
      The patient with JIB developed chronic LF after 25 years. Seven patients were
      transplanted; two died awaiting a graft and one is still on the waiting list.
      After LT, 1 patient developed rapid reappearance of LF at 10 months, requiring
      retransplantation. Two recipients died after LT because of multiorgan failure
      shortly after transplantation. In another case, a de novo cancer was fatal at 6
      years' follow-up. The remaining recipients were doing well. According to this
      survey, the BPD operation carries a potential risk of LF. However, because there
      were only 10 cases, we remain unaware of the actual incidence of Scopinaro
      operation-induced LF. We advise strict follow-up of liver function and timely
      dismantling of BPD.

PMID- 21168707
TI  - Outcomes of long-term administration of intravenous hepatitis B immunoglobulins
      for the prevention of recurrent hepatitis B after liver transplantation.
AB  - PURPOSE: The aim of this study was to investigate the safety and efficacy of
      lifelong therapy with intravenous hepatitis B immunoglobulins (i.v. HBIg) to
      prevent recurrence of hepatitis B after orthotopic liver transplantation (OLT).
      METHODS: This was a single-center retrospective study of the long-term outcome of
      56 patients who were transplanted for active hepatitis B-related liver disease.
      In addition to i.v. HBIg, patients received antiviral therapy for at least 1
      year. RESULTS: 1-, 5-, and 10-year survival rates were 95%, 82%, and 80%,
      respectively. None of the patients died due to hepatitis B virus (HBV)-related
      complications. In 3 patients (5%), a hepatitis B surface antigen (HBsAg)-negative
      status was not reached. All of these patients had a very high viral load at the
      time of OLT. HBsAg and HBV DNA reappeared in 6 patients (11%): In 1 patient,
      recurrence occurred 9 months after OLT while still under combination treatment
      with lamivudine, and 2 patients were temporarily treated abroad with
      intramuscular HBIg. Only 3 patients suffered from HBV recurrence while under
      monotherapy with i.v. HBIg. No serious side effects to i.v. HBIg were reported
      during this long-term follow-up. CONCLUSION: Lifelong administration of i.v. HBIg
      is safe, and recurrence of HBV disease occurred only in a minority of the
      patients during long-term follow-up. Prognosis of HBV-related OLT with this
      therapy is excellent.

PMID- 21168708
TI  - Early arterial revascularization after hepatic artery thrombosis may avoid graft
      loss and improve outcomes in adult liver transplantation.
AB  - BACKGROUND: Hepatic artery thrombosis (HAT) represents a devastating complication
      after liver transplantation (LT), occurring in 1.6%-9.2% of adult recipients.
      Treatments of HAT include thrombectomy and thrombolysis (with or without redo of
      the arterial anastomosis), percutaneous thrombolysis through an angiogram, liver
      retransplantation, and clinical observation. METHODS: We retrospectively analyzed
      data from 739 adult LTs between January 1992 and September 2009. HAT was
      classified as early (E-HAT), when occurring within the first 30 days after LT, or
      late HAT (L-HAT), when diagnosed from the 2nd month onward. HAT suspected
      clinically was confirmed by Doppler ultrasound and angiography in all cases.
      Attempted revascularization was defined as early (ER) if performed within the
      first 2 weeks after LT and late (LR) if performed between 15 and 30 days.
      RESULTS: After a median follow-up (FU) of 62 months (range, 1-227 months), HAT
      occurred in 31/739 grafts (4.3%). E-HAT was recorded in 25/31 cases (3.4%) and L
      HAT in 11/31 cases (0.8%). ER was performed in 20/31 patients (65%) leading to
      62% graft salvage; it was 81% when the revascularization was performed within the
      first week after LT (P = ns). LR was unsuccessful in all cases (P = .08). The
      overall incidence of BC among rescued grafts was 54% without graft loss during
      FU. Graft survival was 79% versus 71%; and 50% versus 50% at 1 and 3 years for E
      HAT and L-HAT, respectively (P = ns). CONCLUSIONS: Urgent revascularization in
      cases of early HAT may decrease graft loss, especially when performed within the
      first week after LT, with improved overall outcomes.

PMID- 21168709
TI  - Air embolism during liver procurement: an underestimated phenomenon? A pilot
      experimental study.
AB  - BACKGROUND: Intrahepatic air embolism can occur during liver transplantation,
      jeopardizing the posttransplant outcome. Until now, the role of the procurement
      in the origin of intrahepatic air remains unclear; it might be underestimated. In
      this pilot study using magnetic resonance imaging (MRI), we observed a
      substantial amount of air trapped in porcine livers during multiorgan
      procurement. We quantified the amount of air, examining whether it could be
      reduced by avoiding direct contact of air with the lumen of the hepatic
      vasculature during procurement and back-table preparation. METHODS: Five livers
      (control group) were procured according to standard techniques for comparison
      with 6 livers (modified group) where air could not enter into the livers due to
      clamping of the vasculature. MRI was performed during continuous machine
      perfusion (MP) preservation there after. We counted the number of black signal
      voids on T(2)*-weighted images, which were indicative of air bubbles within the
      hepatic contour. Additionally, an MRI contrast agent (gadolinium-diethylene
      triamine pentaacetic acid [Gd-DTPA]) was injected into the hepatic artery and
      circulated by MP. Insufficiently perfused areas with less contrast enhancement
      were analyzed quantitatively in T(1)-weighted images and expressed as the
      percentage of total liver volume. RESULTS: The images of the control livers
      showed more air bubbles compared with the modified group (45 +/- 27 vs 6 +/- 3; P
      = .004). The percentage of insufficiently perfused areas was higher among the
      control compared with the modified group (28.0 +/- 15.8% vs 2.6 +/- 4.6%; P =
      .047) on first-pass postcontrast T(1)-weighted images. After recirculating the
      contrast agent, insufficiently perfused areas showed similar localizations and
      contours within every liver. CONCLUSION: These data suggested that a substantial
      amount of air enters into the hepatic microcirculation through direct contact of
      air with the hepatic vasculature during standard procurement and back-table
      preparation. Avoiding opening the hepatic vessels to air substantially reduced
      this phenomenon.

PMID- 21168710
TI  - Diagnostic value of antibodies against Pseudomonas aeruginosa in bronchoalveolar
      lavage fluid after lung transplantation.
AB  - BACKGROUND: Pseudomonal airway colonization is a risk factor for chronic
      allograft dysfunction after lung transplantation (LTx). Pseudomonas aeruginosa
      exoproteases are involved in initiating colonization, and immune complexes
      directed against these proteases may activate innate immune responses. OBJECTIVE:
      To investigate whether specific antibodies against pseudomonal proteases could be
      measured in bronchoalveolar lavage (BAL) fluid, whether they are associated with
      innate immune responses, and whether they could identify patients with chronic P.
      aeruginosa colonization after LTx. MATERIALS AND METHODS: BAL fluid from 40
      noncolonized and 25 chronically colonized LTx recipients was retrospectively
      assayed for IgG antibodies against P. aeruginosa alkaline protease (AP), elastase
      (Ela), and exotoxin (Exo), and for BAL total and differential cell counts and IL
      8 protein concentration. RESULTS: BAL anti-Ela and anti-Exo antibody titers were
      significantly increased in colonized compared with noncolonized patients (P =
      .009 and P = .02, respectively), whereas anti-AP titers were comparable (P =
      .79). Antibody titers strongly correlated with each other, and anti-Ela and anti
      Exo titers, but not anti-AP titers, also correlated with BAL total cellularity,
      neutrophilia, and IL-8 protein concentration. Anti-Ela antibodies demonstrated
      the greatest diagnostic value in receiver operating characteristic analysis to
      detect chronic airway colonization (P = .009), followed by anti-Exo (P = .02) and
      anti-AP (P = .79). A combination of all 3 antibodies resulted in overall
      sensitivity of 45% (95% confidence interval [CI], 29.3-61.5), specificity of 88%
      (95% CI, 68.8-97.5), and positive predictive value of 55% (95% CI, 38.5-70.7).
      CONCLUSION: P. aeruginosa proteases in BAL may be associated with local innate
      immune responses, and could have the potential to enable detection of chronic
      colonization after LTx.

PMID- 21168711
TI  - Living related intestinal transplantation for Churg-Strauss syndrome: a case
      report.
AB  - Exceptionally, gastrointestinal involvement of Churg-Strauss syndrome (CSS) may
      require extensive bowel resection resulting in a short bowel syndrome. Living
      related intestinal transplantation (IT) has emerged as an alternative to deceased
      donor IT in the management of patients with irreversible short bowel syndrome.
      Herein, we have presented a 35-year-old patient with isolated intestinal
      involvement of CSS lesions refractory to steroids and azathioprine requiring
      multiple abdominal resections resulting in an ultrashort bowel syndrome. A living
      related IT (from the mother) was performed. She underwent several acute rejection
      episodes treated with additional immunosuppressive therapy. Despite higher doses
      of immunosuppression, these repeated acute rejection episodes eventually evolved
      into a syndrome of chronic allograft rejection. Eventually, owing to her poor
      general condition and to avoid life-threatening infections, transplantectomy was
      inevitable. Recent immunologic studies indicate that peripheral mononuclear cells
      from patients with CSS secrete large amounts of T-helper type 1 and 2 cytokines.
      It is likely that patients with CSS are at higher risk for acute and chronic
      rejection after transplantation.

PMID- 21168712
TI  - Scandiatransplant report 2009.
AB  - Scandiatransplant is the Nordic organ exchange organization that has existed for
      41 years by a close collaboration between transplant centers. It has been
      valuable to ensure the optimal usage of available organs for transplantation.
      Analyzing the database for the past 15 years (1995-2009) revealed that the
      fraction of organ donors in the age category 60 to 90 years has increased
      considerably. The number of retrieved organs from deceased donors increased for
      kidney, liver, and lungs but only slightly for hearts. In the last time period,
      the mean number of organs retrieved per deceased donor counting only those having
      a recipient increased to 3.7 for younger donors and to 2.6 from the older group.
      In 2009, the STAMP (Scandiatransplant acceptable mismatch program) was launched
      to help highly immunized kidney patients. In 2009, kidney transplantations
      exhibited for Norway, 60 per million people (pmp); more than 40 pmp for Sweden
      and for Denmark; approximately 35 pmp for Finland; and more than 20 pmp for the
      living donor kidney transplantations in Iceland. The best year ever within
      Scandiatransplant with respect to total number of organ transplantations from
      deceased and living donors was 2009.

PMID- 21168713
TI  - Procedures and criteria for accepting the renal patient for inclusion on the
      waiting list for kidney transplantation in the Nordic countries.
AB  - BACKGROUND: The overall aim of this study was to survey and analyze the selection
      process for patients awaiting a kidney in the Nordic countries collaborating
      within Scandiatransplant. METHODS: A two-parts questionnaire was sent to one
      senior physician at each of the 10 Scandiatransplant kidney transplantation
      centers that use deceased donors. The first part consisted of questions related
      to the evaluation of a patient for the waiting list. The second part of the
      questionnaire dealt with 12 borderline cases, based on experiences at seven of
      all centers. Answers should be given with the policy of the center in mind. The
      response rate was 100%. RESULTS: Some centers are stricter than others regarding
      limits for body mass index and cardiac ejection fraction. At three centers, human
      immunodeficiency virus-positive patients are not included on the list. Four
      centers have a policy of not including predialysis patients. All centers agreed
      that they would not refrain from acceptance of a patient due to the scarcity of
      organs, if the patient was considered to benefit medically from transplantation.
      Reevaluation of the patient once on the list is done at all centers, focusing on
      cardiovascular problems. Only a few respondents were positive to the idea of
      common Nordic guidelines for investigations or for limiting values. CONCLUSIONS:
      We concluded that there are some, mainly small, differences among Nordic
      countries regarding procedures and criteria for acceptance of patients on the
      waiting list for kidney transplantation. The interest in common guidelines is
      limited.

PMID- 21168714
TI  - What are we waiting for? Analyses of factors influencing cold ischemia time.
AB  - INTRODUCTION: Cold ischemia time (CIT) influences long-term graft survival after
      deceased donor (DD) kidney transplantation. The aim of the present study was to
      identify factors that influenced CIT at our institution, seeking to lay ground
      for improvement. PATIENTS AND METHODS: Patients who underwent DD kidney
      transplantations from November 2008 to April 2009 were included in the study. In
      a prospective protocol the times for various events were registered. The 40 DD
      kidney transplantations included 26 "paired" kidneys from the same donor and 14
      "single" kidneys. RESULTS: The mean CIT was 15.2 hours +/- 4.2 hours (range, 7.0
      23.9). "First kidney" was 13.3 hours +/- 3.4 versus 19.2 +/- 2.8 hours for the
      "second kidney" (P < .001). The waiting time for the operating room (OR) was 2.4
      hours (range, 0-12 hours). Twenty-five percent of the patients waited more than 4
      hours. Patients arriving at the hospital at the same time as or before the kidney
      retrieval showed a CIT of 13.4 +/- 3.9 hours compared with 17.4 +/- 3.4 hours for
      patients that arrived after the retrieved kidney (P < .01). CONCLUSION: We
      identified factors influencing CIT that could lay the foundation for improvement.
      An extended cooperation and exchange with another transplantation unit for the
      "second kidney" could reduce the CIT. To reduce the waiting time for OR at the
      hospital to less than 2 hours and to get the recipient into the hospital before
      the kidney arrives are efforts that could reduce CIT.

PMID- 21168715
TI  - Conversion from calcineurin inhibitor to either mycophenolate mofetil or
      sirolimus improves renal function in liver transplant recipients with chronic
      kidney disease: results of a prospective randomized trial.
AB  - BACKGROUND: Chronic kidney disease (CKD) has emerged as a significant cause of
      morbidity and a risk factor for mortality after orthotopic liver transplantation
      (OLT). The use of calcineurin inhibitor (CNI)-based immunosuppression is an
      important etiologic factor for developing CKD. CNI discontinuation or
      minimization protocols with replacement of the CNI with non-nephrotoxic drugs,
      such as mycophenolate mofetil (MMF) or sirolimus (SRL), may have the potential to
      preserve or recover renal function. PATIENTS AND METHODS: In this prospective,
      randomized, single-center study with CNI discontinuation, OLT recipients with CKD
      (measured glomerular filtration rate [GFRm] 15-45 mL/min/1.73 m(2)) were
      randomized to either SRL or MMF-based immunosuppression. The main objective was
      to study the effect of CNI discontinuation on renal function. Secondary aims were
      to assess the frequency of biopsy-proven acute rejection episodes (BPAR) and
      adverse events (AE). Renal function was followed with GFRm using 51-Chromium EDTA
      clearance at baseline, 3 months, and 1 year. Patients were stratified according
      to baseline GFRm > versus <30 mL/min/1.73 m(2). The 25 patients were enrolled for
      MMF (n = 13) or SRL (n = 12). The median age at inclusion was 59 years (range, 25
      66) and the median number of years after OLT was 4.4 (range, 1-13). Twenty-two
      patients were followed up for a year; MMF (n = 12) and SRL (n = 10). RESULTS:
      Mean GFRm for the whole cohort (n = 25) was 31+/-8 mL/min/1.73 m(2) at baseline.
      After 3 months the GFRm (n = 23) increased to 40+/-10 mL/min/1.73 m(2) (P =
      .0001) and at 1 year 42 +/- 11 mL/min/1.73 m(2) (n = 22). There was not
      significant difference between the MMF and the SRL study arms. The cohort (n = 8)
      with baseline GFRm <30 mL showed a 63% (P = .003) increased filtration after 1
      year. There was no significant difference in the frequency or severity of AE
      between the study arms with the exception of oral ulcerations and persistent
      hypertriglyceridemia in the SRL group. Two deaths occurred, 1 in each study arm,
      both probably unrelated to the change in immunosuppression. There were no BPAR
      episodes. CONCLUSION: CNI discontinuation and replacement with either MMF or SRL
      resulted in a significant improvement in renal function even in those patients
      with severe CKD. The protocol was effective with no acute rejection episodes. The
      SRL arm showed a higher frequency of oral apthous ulcerations and
      hypertriglyceridemia. Future studies addressing long-term renal function after
      CNI discontinuation are needed.

PMID- 21168716
TI  - Long-term follow-up of living liver donors.
AB  - OBJECTIVES: At our center living donor liver transplantation (LDLT) represents 4%
      of all transplantations. The aim of this cross-sectional study was to clarify the
      current well-being of the donors, their experiences of being a donor, as well as
      the regenerative capacity of the liver. PATIENTS AND METHOD: Thirty-six healthy
      subjects donated a part of their liver between 1996 and 2007. Thirty-four
      patients participated in the study and completed our questionnaire. We performed
      magnetic resonance imaging (MRI) of the liver, physical examination, and blood
      chemistry. RESULTS: Twenty-three subjects had donated the left lateral segment
      and 11 the right lobe. Their hospital stay ranged from 5-15 days (median, 10).
      Mostly, the sick-leave period was 8-12 weeks and time for recovery was 3-6
      months. Long-term problems were heartburn, abdominal discomfort, incisional
      hernia, and fatigue. Twenty-six (76.5%) subjects viewed the donation experience
      as entirely positive; no one was regretful. Liver function tests were normal. The
      MRI data at follow-up of 13 left lateral segment and 11 right lobe grafts showed
      recovery of the total liver volume to almost preoperative values, mean 1522 +/-
      241 mL versus 1552 +/- 219 mL, respectively. CONCLUSION: Living liver donors
      commonly recovered after 3-6 months, perceiving donation as a positive experience
      with no regret. Durable side effects were mainly heartburn and abdominal
      discomfort, but the symptoms were mostly mild. Liver function was normal. The MRI
      data showed a mean regeneration of liver volume to 98.6% of the preoperative
      values.

PMID- 21168717
TI  - Surgical complications accompanying liver transplantation in Estonia.
AB  - The purpose of this study was to evaluate surgical complications accompanying the
      introduction of orthotopic liver transplantation (OLT) in Estonia. Between 1999
      and 2009, we performed the first 12 liver transplantations. Eight patients were
      males and four were females of age range 12 to 67 years. Their diagnoses were
      cholestatic disease (n = 5); tumor (n = 3); hepatitis C virus cirrhosis (n = 2);
      Budd-Chiari syndrome (n = 1); and cystic fibrosis (n = 1). Technical
      complications occurred in 7/12 patients. The early vascular complications in two
      patients were a suprahepatic vena cava lesion occurring at liver extraction,
      which resulted in uncontrolled suprahepatic bleeding after liver perfusion; the
      recipient died during transplantation. The other case displayed a right
      intrahepatic portal venous thrombosis, which was treated successfully with
      thrombolysis and anticoagulant therapy. Early biliary complications of biliary
      leaks occurred in three patients: two had undergone duct-to-duct reconstructions,
      which were treated by endoscopic retrograde cholangiography that successfully
      managed the anastomotic and recipient cystic duct leaks with a papillotomy and
      stenting. In one patient with a duct-to-jejunum anastomosis, a bile leak stopped
      at 3 weeks but he needed surgical therapy 2 years later due to an anastomotic
      stricture. Severe decubitus occurred in the lumbosacral region of the subjects
      with operating times of 14 hours. They required necretectomy and plastic surgery.
      One of them with postoperative intra-abdominal hypertension also displayed wound
      eventration requiring reoperations. The rate of hepatic (5/12) and extrahepatic
      (3/12) surgical complications, as well as of 1-year survival (9/12), in our
      period of implementation of OLT were satisfactory to continue OLT development in
      Estonia.

PMID- 21168718
TI  - Control of early Aspergillus mortality after lung transplantation: outcome and
      risk factors.
AB  - Historic treatment strategies in our institute had resulted in 10% Aspergillus
      mortality within the first posttransplant year. Despite nebulized amphotericin B
      (nAmB) prophylaxis, a significant incidence of Aspergillus infection, usually
      with poor outcome, is still reported. The aim of this single-center retrospective
      study was to evaluate the outcomes of patients receiving either standard nAmB or
      additional systemic caspofungin prophylaxis for selected high-risk patients. We
      also tried to define independent risk factors for either fungal infection or
      death. We followed 76 consecutive lung transplant patients performed at our
      center between 2002 and 2010 from the day of transplantation. The median follow
      up duration was 953 days (2.6 years; range, 16-2,751 days). The endpoints were
      postoperative Aspergillus colonization or disease or death due to any cause. All
      patients received either nAmB deoxycholate (nAmBd, 15 patients) or nAmB lipid
      complex (nAmBLC, 61 patients). In addition, 33 patients also received short-term
      caspofungin prophylaxis. The overall cumulative mortality during the entire
      follow up was 14.5%. No clinically confirmed invasive Aspergillus infections
      (IPA) occurred during the first 2 postoperative years; however, there was 1
      possible and 1 probable IPA. One patient died of bronchiolitis obliterans and IPA
      at 2 years 3 months. Twelve patients showed transient Aspergillus colonization.
      The antifungal prophylactic regimens were well tolerated. The risk factors for
      death were age >55 years and postoperative Aspergillus detection (P = .011 and P
      = .015, respectively). Preoperative Aspergillus colonization/disease was not a
      risk factor for death (P = 1.000). The strongest predictor of death was age >55
      years, due to the elder probably being more susceptible to the adverse effects of
      immunosuppressants. Postoperative detection of Aspergillus still seems to be an
      indicator of a poorer outcome. Preoperative Aspergillus colonization is not
      necessarily a threat with prompt institution of antifungal prophylaxis.

PMID- 21168719
TI  - Natural killer group 2 member D cell recruitment driven by major
      histocompatibility complex class I chain-related antigens A and B: a possible
      mechanism during acute intestinal allograft rejection in the mouse.
AB  - Intestinal allograft rejection occurs frequently despite potent T-cell depletion
      protocols. We investigated the interaction of major histocompatibility complex
      class I chain-related antigens A and B (MICA/B; a ligand for natural killer [NK]
      cells) and NK group 2 member D (NKG2D) cells as an alternative mechanism for
      acute rejection (AR) of the intestinal graft. Heterotopic intestinal
      allotransplantation was performed from BalbC to C57Bl mice. Samples of grafted
      and native intestine were obtained at days 1, 3, 6, and 8 after transplantation
      (n = 4-6). We performed immunostaining for MICA/B and NKG2D. Moderate AR with
      increased crypt apoptosis was observed at day 6 and advanced AR with crypt
      destruction and mucosal sloughing was present by day 8. Low MICA/B levels were
      observed in grafted and native intestines on day 1. MICA/B expression gradually
      increased in the grafts during AR but not in the native intestines. The up
      regulation was found mostly in the crypts. NKG2D+ cell counts that increased in
      the graft colocalized with MICA/B. The increase was most prominent in the crypt
      and villus. Together, these results suggest that MICA/B up-regulation and its
      subsequent interaction with the NK cells may represent an important link between
      innate and adaptive immune responses early after intestinal transplantation.

PMID- 21168720
TI  - The practical, moral, and ethical considerations of the new Israeli law for the
      allocation of donor organs.
AB  - There is a worldwide shortage of organs for transplantation; the number of
      patients on the waiting list exceeds the supply of available organs. The demand
      for organ donation is particularly concerning in Israel. A new Israeli law has
      been instituted to give those who sign donor cards allocation priority if they
      are ever in need of an organ transplant themselves. A number of variations on
      this paradigm that considers the willingness of patients to donate their own
      organs have since been proposed; however, the new Israeli policy for organ
      donation is the first time such a law has been implemented nationally.
      Prioritization of organ allocation to donors comes with a significant moral and
      ethical debate, and since its implementation in January 2010 there has been much
      controversy surrounding the new policy. This article provides a description of
      the new Israeli plan, specifically focusing on the practical, moral, and ethical
      debates surrounding the new system.

PMID- 21168721
TI  - Seropositive abdominal and thoracic donor organs are largely underutilized.
AB  - The aim of this study was to describe the epidemiology and utilization of anti
      hepatitis B core protein(+) and anti-hepatitis C virus(+) organ donor referrals
      in a large organ procurement organization. Between 1995 and 2006, 3,134 deceased
      organ donor referrals were tested for anti-HBc and anti-HCV using commercial
      assays. The prevalence of anti-HCV(+) organ donor referrals significantly
      increased from 3.4% in 1994-1996 to 8.1% in 2003-2005 (P < .001), whereas the
      prevalence of anti-HBc(+) organ donor referrals remained unchanged at 3%-4% (P =
      .20). The 112 anti-HBc(+) (3.5%) and 173 anti-HCV(+) (5.5%) organ donor referrals
      were significantly older and more likely to be noncaucasian than seronegative
      organ donor referrals (P < .02). The procurement and utilization rates of
      seropositive thoracic and abdominal donor organs were significantly lower
      compared with seronegative organ donors (P < .0001). However, liver utilization
      rates significantly increased from anti-HBc(+) donors over time (21% vs 46%; P =
      .026), whereas utilization of anti-HCV(+) liver donors remained unchanged over
      time (5% vs 18%; P = .303). In summary, the proportion of anti-HCV(+) organ donor
      referrals has significantly increased and the proportion of anti-HBc(+) organ
      donor referrals has remained stable. Both thoracic and abdominal organs from
      seropositive donors are largely underutilized.

PMID- 21168722
TI  - S-nitroso-N-acetylcysteine: a promising drug for early ischemia/reperfusion
      injury in rat liver.
AB  - BACKGROUND/AIMS: Ischemia-reperfusion (I/R) injury is among the major causes of
      poor graft function early after liver transplantation that adversely influences
      patient survival. A variety of mediators have been implicated in the pathogenesis
      of I/R vascular injury, including nitric oxide (NO). Because of the beneficial
      effects of NO during preconditioning and reperfusion, strategies to prevent or
      ameliorate I/R injury through the stimulation of hepatic NO production are an
      area of significant clinical interest. We evaluated the role of S-nitroso-N
      acetylcysteine (SNAC) as an NO donor in the prevention of liver I/R injury in an
      animal model. METHODS: Adult male Wistar rats were randomly assigned to 3
      experimental groups containing 5 animals each: the University of Wisconsin (UW)
      solution group; SNAC solution group; and SNAC-containing UW solution (SNAC+UW)
      group. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and
      lactate dehydrogenase (LDH) were determined in samples of the cold storage
      solution at 2, 4, and 6 hours of preservation. After 6 hours of cold storage, We
      applied a 15-minute reperfusion period. Thereafter, the reperfusion was
      interrupted with blood samples obtained to measure AST, ALT, LDH, and
      thiobarbituric acid reactive substances (TBARS). Hepatic fragments were processed
      for histologic analysis, and to determine of TBARS, catalase, and glutathione
      levels. RESULTS: During cold preservation, AST and LDH were significantly lower
      among the SNAC than the UW group or the SNAC+UW group (P = .004 and P = .03,
      respectively). ALT was comparable among the groups (P = .3). After reperfusion,
      serum levels of AST, ALT, and LDH, as well as of hepatic TBARS and catalase
      showed no differences among the groups. Glutathione concentration was lower in
      the SNAC and SNAC+UW group (P < .001) compared with the UW group. We did not
      observe histologic signs of preservation injury. CONCLUSION: The SNAC solution
      showed a greater protective effect to preserve rat livers during cold storage,
      but it was comparable with UW.

PMID- 21168723
TI  - B-type natriuretic peptide pretreatment attenuates heart ischemia-reperfusion
      injury in rats.
AB  - BACKGROUND: Graft dysfunction following transplantation is due to ischemia
      reperfusion (IR) injury. B-type natriuretic peptide (BNP) has been shown to
      attenuate ischemia-reperfusion (IR) injury in animals. We designed this
      experiment to evaluate the effects of BNP pretreatment on IR-induced heart
      injury. METHODS: A rat model of myocardial IR injury was established by ligating
      the left descending coronary artery for 30 minutes before a 2-hour reperfusion.
      We randomly divided 47 Sprague-Dawley rats into six groups: sham operation (n =
      6), IR (n = 9), IR + BNP 0.001 MUg/(kg.min; n = 8); IR + BNP 0.005 MUg/(kg.min; n
      = 8); IR + BNP 0.01 MUg/(kg.min; n = 8); and IR + BNP 0.03 MUg/(kg.min; n = 8).
      During the processes, lead ECG was traced continuously to note arrhythmias caused
      by reperfusion. Serum levels of creatine kinase-MB (CK-MB) and lactate
      dehydrogenase (LDH) were measured at 2 hours after reperfusion. RESULTS: The BNP
      treated animals showed a significantly reduced incidence of ventricular
      arrhythmias caused by reperfusion (P < .05). They showed a dosage-dependent
      marked decrease in levels of serum CK-MB and LDH compared with the IR only group
      (P < .05). CONCLUSIONS: BNP pretreatment protected the myocardium of rats against
      IR injury, in a dose-dependent manner.

PMID- 21168724
TI  - Association between interleukin-3 gene polymorphism and acute rejection after
      kidney transplantation.
AB  - BACKGROUND: Acute rejection (AR) after kidney transplantation resulting from
      alloimmune responses has a negative effect on graft survival. AR is mainly caused
      by T-cell immune responses activated by cytokines, including interleukin (IL)-2, 
      4, and -7. Many reports have shown that single nucleotide polymorphisms (SNPs) of
      these cytokines can affect the occurrence of AR. IL-3, which is secreted by
      activated T cells, can mediate AR. Our study sought to investigate the
      association between SNPs of the IL3 gene and the occurrence of an AR episode
      (ARE). METHODS: We analyzed 3 SNPs of IL3 (rs181781, rs2073506, and rs40401)
      among 330 renal recipients, 60 of whom had developed an ARE. SNPs of the IL3
      gene, including 1 exonic SNP (rs40401) and 2 regulatory thought to be promoter
      SNPs (rs181781 and rs2073506). RESULTS: The genotypes of 60 ARE subjects and the
      270 patients without AR demonstrated a significant relationship between genotype
      frequencies and the SNPs. The occurrence of an ARE was associated with rs181781
      (P = .041, dominant model), rs2073506 (P = .009, codominant 1 model; P = .003,
      dominant model), and rs40401 (P = .014, recessive model). Among haplotypes, AAT
      showed a significant association with ARE. (P = .0033). CONCLUSION: Our results
      suggest that IL3 gene polymorphisms were associated with this event.

PMID- 21168725
TI  - Interferon-gamma +874 polymorphism in the first intron of the human interferon
      gamma gene and kidney allograft outcome.
AB  - BACKGROUND: Despite advances in immunosuppressive therapy in the past decade,
      allograft rejection remains an important cause of kidney graft failure. Cytokines
      play a major role in the inflammatory and immune responses that mediate allograft
      outcomes. Several studies have shown that the production of cytokines varies
      among individuals. These variations are determined by genetic polymorphisms, most
      commonly within the regulatory region of cytokine genes. The aim of the present
      study was to assess the effect of allelic variation on acute rejection episodes
      (ARE) or chronic allograft nephropathy (CAN) after kidney transplantation.
      METHODS: To determine a possible correlation between the interferon (INF)-gamma
      +874 polymorphism and kidney allograft outcome, we isolated genomic DNA from 74
      patients who underwent isolated kidney allografts and were classified into 2
      groups--a rejection and a nonrejection group--for comparison with a control group
      of 163 healthy subjects. RESULTS: We genotyped INF-gamma +874 polymorphisms in
      all groups. The transplant group showed a significantly increased homozygous
      genotype T/T (P = .0118) compared with healthy controls. Similarly, considering
      only patients with CAN, the homozygous genotype T/T (P = .0067) was significantly
      increased compared with the healthy controls. The rejection group indicated a
      significant increased homozygous genotype T/T compared with the control group (P
      = .0061). CONCLUSION: Homozygous genotype T/T was associated with increased
      levels of INF-gamma and greater numbers among the rejection and CAN cohorts.

PMID- 21168726
TI  - Why rejections are not biopsy proven: frequency and reasons.
AB  - BACKGROUND: Rejection still has a fundamental impact on patient and graft
      survivals after renal transplantation. Published studies vary widely in their
      reporting of biopsy-proven acute rejection (BPAR) and non-BPAR rates. We
      undertook a systematic search of existing publications for reasons explaining
      this difference. Additionally, we analyzed our own population, which has a
      clearly defined biopsy strategy, to further investigate the rate of non-BPAR in
      routine clinical practice. METHODS: From large, multicenter, randomized,
      controlled trials investigating immunosuppressive regimens in de novo kidney
      transplant recipients, we extracted the rates of all reported rejections ("total"
      rate) versus BPAR. Non-BPAR was defined as the difference between "total" and
      BPAR. Additional analyses were performed for potential influencing factors, such
      as year of publication, number, and mean age of patients recruited and impact
      factor of the journal at the time of publication. We scanned all de novo adult
      patients undergoing kidney transplantation in our center between 1996 and 2004
      for rejection episodes during the first year. RESULTS: The median rate of non
      BPAR within the first year in 27 papers was 7% (range, 0%- 16.9%). Similarly, the
      relative proportion of non-BPAR showed large differences. We could not identify
      potential influencing factors to explain the large variability. Among our
      population, 136/365 patients (37.3%) experienced acute rejection episodes, with
      BPAR diagnosed in 90/365 patients (24.7%), yielding an absolute 12.6% rate of non
      BPAR. CONCLUSION: Even centers with a well-defined biopsy strategy show a
      substantial proportion of non-BPAR episodes. Therefore, complete reporting of
      both BPAR and non-BPAR is important for the proper interpretation of study
      results.

PMID- 21168727
TI  - Aspergillus spondylodiscitis in solid organ transplant recipients.
AB  - BACKGROUND: Transplantation practices have had a significant effect on the
      epidemiology of invasive Aspergillosis. Aspergillus spondylodiscitis is rare in
      transplant recipients. The optimal treatment has yet to be defined because of the
      rarity of such cases. This article reviews the available literature on
      Aspergillus spondylodiscitis in solid organ transplant recipients and provides
      recommendations on its management. METHODS: We identified 15 cases of Aspergillus
      spondylodiscitis in transplant recipients. Most patients were heart transplant
      recipients. Back pain was the mode of presentation in all patients. Most cases
      were afebrile. The dominant location was the lumbar spine. RESULTS: Aspergillus
      fumigatus was responsible for 84.62% of cases and A flavus for 15.38%. The
      overall recovery rate was 66.67%. Delay in diagnosis remained a major impediment
      to the successful treatment of spinal aspergillosis. Treatment included
      antifungal therapy alone or combined with surgery. Initial therapy with
      voriconazole could lead to better curative effects. CONCLUSION: Combined medical
      and operative interventions are recommended for treatment.

PMID- 21168728
TI  - Individualizing early use of sirolimus in renal transplantation.
AB  - One of the main goals in the current care of kidney transplant recipients is to
      extend long-term graft survival. Efficacious immunosuppressive agents devoid of
      nephrotoxicity are needed. In human clinical transplantation, sirolimus combined
      with other immunosuppressive drugs has proven to be a powerful immunosuppressant
      capable of preventing acute graft rejection, as well as of improving renal
      function, renal histology, and graft survival when compared with
      immunosuppressive regimens that include calcineurin inhibitors. The valuable
      experience gained through many clinical studies allows clinicians to plan
      sirolimus use. We present a review of the clinical experience and literature
      review on the use of sirolimus in the first 12 months posttransplantation.

PMID- 21168729
TI  - Steroid avoidance in two-haplotype-matched living donor renal transplants with
      basiliximab induction therapy.
AB  - BACKGROUND: Induction therapy and haplotype matching are utilized to mitigate
      immunologic risk in renal transplantation. The incidence of acute rejection (AR)
      of renal allografts has been reported to be as low as 9.3% within the first year
      among two-haplotype-matched siblings with no induction and triple-drug
      maintenance immunosuppression. We report our use of basiliximab induction in a
      series of two-haplotype-matched living donor renal transplants (LDRT). METHODS:
      We retrospectively reviewed 25 patients who received a two-haplotype-matched LDRT
      with basiliximab induction therapy. The primary endpoints were acute rejection
      (AR) episodes at 6 and 12 months and 1-year patient and graft survival rates. The
      secondary endpoints were the incidence of delayed graft function (DGF),
      cytomegalovirus (CMV), and BK virus (BKV). RESULTS: The rate of AR at 6 months
      was 0% (0/25) and 4% (1/25) at 12 months. The 1-year graft and patient survival
      rates were 100%. The incidence of DGF was 4% (1/25), while the incidences of CMV
      and BKV were 0%. CONCLUSION: Basiliximab induction therapy with a steroid-sparing
      regimen yields favorable results in two-haplotype-matched LDRT, including a
      notable reduction in the rates of AR as compared to triple-drug maintenance
      immunosuppression without induction. These patients have excellent graft survival
      with no increased incidences of secondary infections.

PMID- 21168730
TI  - Diagnostic performance of serum cystatin C and serum creatinine in the prediction
      of chronic kidney disease in renal transplant recipients.
AB  - BACKGROUND: Chronic kidney disease (CKD) has adverse impacts on mortality and
      morbidity of renal transplant recipients. Serum cystatin C (sCysC) is a novel
      marker in predicting the CKD. We therefore compare sCysC and serum creatinine
      (sCr) with the aim of improving the detection of CKD in renal transplant
      recipients. METHODS: We enrolled 106 renal transplant recipients and estimated
      glomerular filtration rates (GFR) using the Cockcroft-Gault (GFR(CG)) and the
      abbreviated Modification of Diet in Renal Disease (GFR(aMDRD)) formulae. We
      defined CKD as the presence of structural or functional kidney damage,
      irrespective of the diagnosis. Comparisons of sCysC and sCr in detecting CKD were
      analyzed. RESULTS: sCysC correlates with sCr significantly (r = 0.87; P < .001).
      The receiver operating characteristic curve demonstrates that sCysC has a better
      specificity and area under the curve, but less sensitivity than sCr in predicting
      CKD in renal transplant recipients if GFR is estimated by GFR(CG). Additionally,
      if GFR was estimated by GFR(aMDRD), the role of sCysC or sCr in prediction of CKD
      was comparable. CONCLUSION: sCysC may be better than sCr to detect CKD in renal
      transplant recipients using the GFR(CG).

PMID- 21168731
TI  - Analytical performance of the Abbott Architect i2000 tacrolimus assay in Chinese
      patients after renal transplantation.
AB  - BACKGROUND: Monitoring of tacrolimus concentrations has played a crucial role to
      control the efficacy versus adverse effects of treatment, because of the drug's
      narrow therapeutic range, inter- and intraindividual variabilities, and drug
      interactions mediated by hepatic cytochrome P450. Therefore, the stability of
      methods to monitor tacrolimus is of major importance. This study evaluated the
      analytical performance of the Abbott Architect i2000 tacrolimus assay, which was
      recently released in China to monitor tacrolimus therapy. We compared the results
      using the Abbott Architect i2000 Tacrolimus assay with the traditional Abbott IMx
      method. METHODS: We measured concentrations of tacrolimus in 100 samples from
      renal transplant patients by Architect i2000 and the commonly used Abbott IMx.
      RESULTS: We observed that the total %CV of the Architect i2000 assay was <10%,
      both at low and high concentration levels, with a functional sensitivity of <0.5
      ng/mL. The Architect i2000 assay was linear over the reportable range with
      recoveries ranging from 90.6% to 106.7%. In addition, this assay was not affected
      by high concentrations of hemoglobin, lipids, or bilirubin in the samples. The 2
      assays yielded similar results. The regression equation obtained from the Passing
      Bablok analysis was: y = 0.8788x - 0.3485 with a Spearman correlation coefficient
      (r) of 0.9922. The bias plot between the Architect i2000 and Abbott IMx assay
      yielded an average negative bias (-1.4 ng/mL). CONCLUSION: We concluded that,
      because of its high precision and sensitivity, low cross-reactivity, and
      acceptable accuracy, the Architect i2000 assay is a suitable alternative to
      monitor tacrolimus concentrations in renal transplant recipients.

PMID- 21168732
TI  - Possible defect of T suppressor cell subpopulation in patients with kidney acute
      rejection.
AB  - CD8(+)CD28(-) forkhead box P3 (Foxp3(+)) T suppressor (Ts) lymphocytes are
      antigen-specific cells capable of inducing tolerogenic antigen-presenting cells
      by up-regulation of inhibitory receptors immunoglobulin-like-transcripts -3 and 
      4 and down-regulation of costimulatory molecules. Our study sought to investigate
      the relation between the level of peripheral CD8(+)CD28(-)Foxp3(+) Ts cells and
      kidney allograft outcomes. The project included 44 kidney transplantation
      patients. During the 6-month period following transplantation an acute rejection
      episode (ARE) was diagnosed in 11 patients based on biopsy results using the
      Banff criteria. Peripheral blood samples collected at 1 day before as well as 14
      and 30 days after transplantation were tested for CD8(+)CD28(-)Foxp3(+) T cells
      by means of flow cytometry. Values were considered significant when P < .05.
      Cytometric analysis did not show significant differences between the groups in
      pretransplant levels of peripheral CD8(+)CD28(-)Foxp3(+) Ts cells (P > .05);
      however, the posttransplantation analysis showed a higher mean level of Ts cells
      in nonrejection (NONARE) versus acute rejection (ARE) patients (P < .0001). This
      observation suggested that dysfunction of CD8(+)CD28(-)Foxp3(+) Ts cells observed
      in ARE patients may contribute to these episodes. Interestingly, we observed
      similar results with respect to peripheral CD4(+)CD25(+)Foxp3(+) T regulatory
      cells in ARE patients, suggesting impairment of immunoregulatory mechanisms
      (especially within the inducible Foxp3 system) in this group, leading to acute
      renal allograft rejection episodes.

PMID- 21168733
TI  - Rifaximin for the treatment of hepatic encephalopathy.
AB  - BACKGROUND: Previous studies suggest that rifaximin is efficacious in the
      treatment of hepatic encephalopathy. OBJECTIVE: To evaluate the efficacy and
      safety of rifaximin in addition to lactulose in improving hospitalization
      outcomes in patients with hepatic encephalopathy. METHODS: Hospital records of
      patients evaluated for liver transplantation at a single center between January
      2006 and May 2008 were reviewed. Hospitalizations for hepatic encephalopathy and
      other conditions and the incidence of spontaneous bacterial peritonitis and
      adverse events were analyzed. RESULTS: Charts of 65 patients who were treated
      with rifaximin and lactulose were analyzed. Patients received lactulose (20-120
      g/d; lactulose phase) before treatment with rifaximin (400- 1200 mg/d; rifaximin
      phase). During the rifaximin phase, the risk, number, and duration of
      hospitalizations for hepatic encephalopathy were reduced compared with the
      lactulose phase. Treatment, age, and Model for End-Stage Liver Disease score were
      independent predictors of hospitalizations for hepatic encephalopathy (P < .05).
      The rifaximin phase had fewer hospitalizations than the lactulose phase (36 vs
      47, respectively) and a smaller percentage of patients with repeated
      hospitalizations than the lactulose phase (5% vs 14%, respectively; P = .006) for
      conditions other than hepatic encephalopathy. A smaller percentage of patients
      had evidence of spontaneous bacterial peritonitis during the rifaximin phase than
      the lactulose phase (2% vs 12%, respectively; P = .02). Rifaximin was better
      tolerated than lactulose. CONCLUSIONS: Addition of rifaximin to lactulose therapy
      significantly reduced the risk and duration of hospitalizations for hepatic
      encephalopathy.

PMID- 21168734
TI  - Hepatectomy-related hypophosphatemia may predict donor liver dysfunction in live
      donor liver transplantation.
AB  - BACKGROUND: Hypophosphatemia after living-donor liver donation was recently
      reported to not be linked to donor morbidity. However, few studies have examined
      the relationship between hypophosphatemia and hepatic function after hepatectomy
      in live liver donors. In this study, we investigated the relationship between
      postoperative hypophosphatemia and hepatic function in living donors after
      hepatectomy. METHODS: We collected data from 102 live-donor hemihepatectomy
      cases. The severity of hypophosphatemia was categorized as mild (1.5-2.5 mg/dL),
      moderate (1.1-1.5 mg/dL), or severe (<1.0 mg/dL). We compared complications among
      the groups and factors possibly related to the postoperative nadir phosphorus
      levels. RESULTS: One hundred cases (98%) developed mild (n = 56), moderate (n =
      25), or severe (n = 19), hypophosphatemia. Serum phosphate levels began to fall
      on postoperative day (POD) 2, reaching a nadir (1.89 +/- 0.72 mg/dL) on POD 3.
      There was a significant difference in the incidence of postoperative liver
      dysfunction among the 3 groups (P = .027). Moreover, a correlation was identified
      between the incidence and the hypophosphatemia severity (r = 0.549; P = .023).
      The nadir phosphorous level significantly and negatively correlated with the peak
      of total bilirubin (P = .001) and international normalized ratio (P = .004).
      Patients with intravenous phosphorus replacement showed better hepatic function
      and a lower incidence of hepatic dysfunction among the severely hypophosphatemic
      group. CONCLUSION: Hypophosphatemia was predictive of hepatic dysfunction after
      hepatectomy in living donors. Phosphorus replacement may improve recovery of
      hepatic function among living liver donors.

PMID- 21168735
TI  - Dual grafts live donor liver transplantation for acute-on-chronic hepatitis B
      liver failure.
AB  - OBJECTIVE: This study reports the preliminary experience of dual grafts living
      donor liver transplantation (LDLT) for patients with acute-on-chronic liver
      failure (AoCLF) caused by hepatitis B. METHODS: Two patients who demonstrated
      acute-on-chronic hepatitis B liver failure and portal hypertension with Model for
      End-Stage Liver Disease (MELD) scores of 42 and 37, respectively, underwent dual
      LDLT grafts including one right lobe without a middle hepatic vein and one left
      lobe because the graft-to-recipient body weight ratio of the right lobe grafts
      were 0.53% and 0.66%. The donors and the recipients have been followed for over 1
      year. RESULTS: Mortality and operative complications were not observed in the
      donors or recipients. At present, the donors and recipients have returned to
      their daily routine. No prisoners or organs from prisoners were used to obtain
      these data. CONCLUSION: Dual LDLT grafts including one right lobe without the
      middle hepatic vein and one left lobe may be a possible therapeutic option for
      subjects with acute-on-chronic hepatitis B-induced liver failure.

PMID- 21168736
TI  - Management of intra-abdominal drain after living donor liver transplantation.
AB  - BACKGROUND: There have been few reports on the management of intra-abdominal
      drains after living donor liver transplantation (LDLT). We retrospectively
      investigated changes in ascitic data related to management of an intra-abdominal
      drain. PATIENTS AND METHODS: Between March 2008 and June 2009, we performed 28
      LDLT. On the first and the fifth postoperative day (POD) after LDLT, we examined
      the number of ascites cells and cell fractions as well as performed biochemical
      examination and cultures. RESULTS: The day of removal of the drain for massive
      ascites (10 mL/kg/d or more) was 14.2 +/- 5.4 POD; for less than 10 mL/kg/d it
      was 8.7 +/- 1.9 POD (P < .001). Nine patients were ascites culture positive; long
      term placement of the drain caused an infection in two patients. CONCLUSIONS:
      When the amount of ascitic fluid on the fifth POD after LDLT was small, it was
      important to assess the properties of the ascitic fluid because of the
      possibility of a drain infection or of poor drainage. If the ascitic neutrophil
      count is less than 250/mm(3) or the examined ascites is normal, intra-abdominal
      drains should be removed.

PMID- 21168737
TI  - Dual left lobe living donor liver transplantation using donors unacceptable for
      right lobe donation: a case report.
AB  - Living donor liver transplantation (LDLT) has become a viable alternative for end
      stage liver disease. The shortage of brain-dead donors has led to development of
      advanced surgical approaches. Dual lobe LDLT has been performed successfully in
      the recent years. The major indication for this complex procedure has been
      insufficient graft size from a single donor or insufficient remnant in the donor.
      We performed a dual left lobe LDLT using 2 donors who were unacceptable for right
      lobe donation.

PMID- 21168738
TI  - Availability of anesthetic effect monitoring: utilization, intraoperative
      management and time to extubation in liver transplantation.
AB  - Titration of volatile anesthetics to anesthetic effect monitoring using the
      bispectral index (BIS) has been shown to decrease anesthetic requirements and
      facilitate recovery from anesthesia unrelated to liver transplantation (OLT). To
      determine whether availability of such monitoring influences its utilization
      pattern and affect anesthetic care and outcomes in OLT, we conducted a
      retrospective analysis in recipients with and without such monitoring. We
      evaluated annual BIS utilization over a period of 7 years, and compared 41 BIS
      monitored patients to 42 controls. All received an isoflurane/air/oxygen and
      opioid-based anesthetic with planned postoperative ventilation. Data collection
      included age, body mass index (BMI), gender, Model for End-stage Liver Disease
      (MELD) score, and time to extubation (TtE). Mean preanhepatic, anhepatic, and
      postanhepatic end-tidal isoflurane concentrations were compared, as well as BIS
      values for each phase of OLT using the Kruskal-Wallis and Wilcoxon signed-rank
      tests, respectively. The use of anesthetic effect monitoring when available
      increased steadily from 15% of cases in the first year to almost 93% by year 7.
      There was no significant difference in age, gender, BMI, MELD, or TtE between
      groups. The BIS group received less inhalational anesthetic during each phase of
      OLT compared to the control group. However, this difference was statistically
      significant only during the anhepatic phase (P = .026), and was clinically not
      impressive. Within the BIS group, the mean BIS value was 38.74 +/- 5.25 (mean +/-
      standard deviation), and there was no difference for the BIS value between
      different transplant phases. Availability of anesthetic effect monitoring as an
      optional monitoring tool during OLT results in its increasing utilization by
      anesthesia care teams over time. However, unless integrated into an
      intraoperative algorithm and an early extubation protocol for fast tracking of
      OLT recipients, this utilization does not appear to provide a clinical benefit
      but instead drives cost.

PMID- 21168739
TI  - Interleukin-2 receptor antagonists in liver transplantation: a meta-analysis of
      randomized trials.
AB  - BACKGROUND: The efficacy and safety of interleukin-2 receptor antagonist (IL-2Ra)
      induction therapy in liver transplantation has not reached a final conclusion.
      This study sought to explore the effects of IL-2Ra therapy on occurrence of
      biopsy-proven acute rejection (BPAR), risk of infection, and other adverse events
      by using meta-analysis. METHODS: We reviewed randomized trials assessing IL-2Ra
      therapeutic effects in liver transplantation. We synthesized published data using
      the random-effects and fixed-effect models, expressing results as relative risk
      (RR) with 95% confidence intervals (CI). RESULTS: Among 12 trials including 3,251
      participants, IL-2Ra significantly reduced the incidence of BPAR (RR 0.82, 95% CI
      0.68-0.99) and de novo diabetes mellitus (RR 0.75, 95% CI 0.62-0.91) within 1
      year. Subgroup analysis showed only daclizumab but not basiliximab treatment to
      significantly benefit BPAR and de novo diabetes mellitus. There were no
      significant differences in the graft losses (RR 1.05, 95% CI 0.85-1.31),
      mortality rates (RR 0.89, 95% CI 0.70-1.13), overall incidences of infection (RR
      0.95, 95% CI 0.87-1.04), incidences of cytomegalovirus infections (RR 0.96, 95%
      CI 0.65-1.44), risks of malignancies (RR 1.06, 95% CI 0.56-2.01), or de novo
      hypertension (RR 0.90, 95% CI 0.79-1.03) or and renal insufficiency (RR 0.81, 95%
      CI 0.56-1.17, P = .26) within 1 year. CONCLUSIONS: The IL-2Ra daclizumab, but not
      basiliximab, shows significant benefit to reduce acute rejection episodes and de
      novo diabetes mellitus within 1 year among patients undergoing liver
      transplantation. There was no evidence of an increased risk of infection or other
      side effects.

PMID- 21168740
TI  - Results of a two-center study comparing hepatic fibrosis progression in HCV
      positive liver transplant patients receiving cyclosporine or tacrolimus.
AB  - A 2-center retrospective analysis was performed in 60 patients undergoing liver
      transplantation for hepatitis C virus (HCV)-related disease (cyclosporine in 20,
      tacrolimus in 40). Mean (+/-SEM) follow-up was 23.6 +/- 22.5 and 22.3 +/- 13.7
      months in patients receiving cyclosporine or tacrolimus, respectively. Clinically
      indicated biopsies were performed in 15/20 cyclosporine patients (75%) and 22/40
      tacrolimus patients (55%; P = .17). The Ishak fibrosis score was significantly
      lower in cyclosporine-treated patients versus tacrolimus-treated patients (mean
      1.7 +/- 0.4 vs 3.1 +/- 0.4; P = .023), as was percentage of fibrosis grade Ishak
      >=4 (7% vs 41%; P = .028). The mean time to moderate fibrosis (Ishak score >=3)
      was 38.2 +/- 15.1 months in cyclosporine patients (4/15) and 23.5 +/- 12.6 months
      in tacrolimus patients (14/22); the difference was not statistically significant
      (P = .09). This retrospective study suggests that cyclosporine-based
      immunosuppression is associated with less severe hepatic fibrosis in HCV-positive
      liver transplant recipients compared with tacrolimus-based regimens, but a larger
      prospective comparative trial is necessary to confirm these findings.

PMID- 21168741
TI  - Prognostic and developmental factors in patients receiving liver transplant due
      to hepatocellular carcinoma: one center's experience in the north of Spain.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent types of
      tumor. The aim of this study was to determine the survival of patients who had
      received liver transplants as a result of the disease. METHODS: This
      observational follow-up study included 150 patients who received liver
      transplantations from June 1994 to December 2007. The study considered
      epidemiological and staging variables, tumor descriptions, and follow-up
      variables. We employed Kaplan-Meier methodology together with a Cox multivariate
      regression analysis. RESULTS: The incidence of tumor relapse was 13.3%, with
      survival rates at 1, 3, and 5 years of 89.3%, 73.1%, and 61.4%, respectively.
      Variables that showed an independent effect to predict mortality were the degree
      of histological differentiation and of macrovascular invasion. Patients with
      poorly differentiated HCC had a 4.03 fold (95% confidence interval [CI]: 1.61
      10.06) greater possibility of dying. Macrovascular involvement increased the risk
      of death (relative risk = 2.23), an effect that was at the limit of significance
      (95% CI 0.99-5.04). CONCLUSIONS: The survival rate was consistent with the
      literature. Poor tumor differentiation and macrovascular involvement were
      independent predictors of mortality.

PMID- 21168742
TI  - Treating hepatocellular carcinoma with sorafenib in liver transplant patients: an
      initial experience.
AB  - Sorafenib has been approved for the treatment of advanced hepatocellular
      carcinoma (HCC). However, there are no data reported on its use in HCC patients
      with localized disease who have undergone orthotopic liver transplantation (OLT).
      Herein, we have reviewed our initial experience with 7 HCC patients who were
      candidates for OLT and were treated with sorafenib. Treating liver transplant
      patients with sorafenib appeared to be safe based upon our limited experience.
      There is a strong need for clinical trials to comprehensively study the safety of
      sorafenib before OLT.

PMID- 21168743
TI  - Total tumor volume predicts recurrence of hepatocellular carcinoma after liver
      transplantation in patients beyond Milan or UCSF criteria.
AB  - BACKGROUND: The aim of tumor-based selection criteria in patients with
      hepatocellular carcinoma (HCC) is to prevent orthotopic liver transplantation
      (OLT) in patients likely to experience recurrence and to maximize OLT
      opportunities for those with a high likelihood of cure. OBJECTIVE: Our aim was to
      assess total tumor volume (TTV) as a selection criterion for OLT in patients with
      HCC beyond Milan or University of California San Francisco criteria. METHODS: We
      identified patients who underwent OLT for HCC between 2002 and 2008. TTV was
      calculated as the sum of the volumes of all tumors on pretransplant imaging
      before any therapy [(4/3)pir(3), where r is the maximum radius of each HCC].
      Univariable and multivariable Cox proportional hazards regression analysis was
      used to assess factors associated with recurrence of HCC. RESULTS: 107 patients
      were included in the study. The mean follow-up was 21 months (interquartile
      range, 11.8-32.5), during which 13 patients (12.1%) experienced recurrence of
      HCC. Twenty-nine patients (27.1%) had HCC beyond the Milan criteria. A TTV cutoff
      value of 33.5 cm(3) was chosen on the basis of the risk of recurrence by using a
      receiver operating characteristic curve. Patients beyond the Milan criteria with
      TTV <33.5 experienced less recurrence (13.3% vs 42.8%; P < .001) and higher
      survival (13.3% vs 57.1%; P = .006) than those who were beyond the Milan criteria
      with TTV >=33.5. Similarly, TTV predicted HCC recurrence and survival in those
      beyond the UCSF criteria. CONCLUSION: TTV is useful in identifying patients at
      risk of tumor recurrence and poor survival among those with tumor burden beyond
      traditional criteria, and it may improve the selection of OLT candidates.

PMID- 21168744
TI  - Self-expanding metallic stent placement with laryngeal mask in lung transplant
      recipients.
AB  - BACKGROUND: Bronchial stent insertion is a suitable method to treat airway
      complications. We present our experience with laryngeal mask airway (LMA) for
      stent insertion in lung transplant (LT) recipients. METHODS: From April 2007 to
      March 2009, 27 LT recipients underwent insertion of self-expanding nitinol stents
      to manage airway complications after LT, using LMA for general anesthesia. All
      procedures were performed with flexible fiberoptic bronchoscopy without
      fluoroscopy; stent release was visualized with ultrathin bronchoscopes. We
      followed technical success, safety, improvement of lung function, and clinical
      symptoms. RESULTS: Forty-one stents were inserted in 27 patients in 32 sessions.
      The indications for stent insertion were necrotic lesions (7%) and obstructive
      lesions (90%). Technical success and safety were 94%. Twice, the stent
      dislocated, requiring replacements. In 91% of patients, postinterventional
      improvement in graft function (1 minute forced expiratory volume) was >10% after
      the intervention. Improvement of clinical symptoms was achieved in 94%. The
      median procedure time was 38 minutes (range, 30-85 minutes). CONCLUSIONS: LMA
      offered an excellent condition for stent insertion in LT recipients with airway
      complications. It provided adequate ventilation and safe airway control during
      the procedure. This technique may serve as alternative to established techniques
      using fluoroscopy and rigid bronchoscopy.

PMID- 21168745
TI  - Black hairy tongue after allogeneic stem cell transplantation: an unrecognized
      cutaneous presentation of graft-versus-host disease.
AB  - Black hairy tongue (BHT) is an unusual condition in adults characterized by
      marked accumulation of keratin on the dorsum of the tongue, resulting in a hair
      like appearance. Herein, we have described 15 patients developing BHT after
      allogeneic stem cell transplantation (allo-SCT). BHT was generally accompanied by
      other cutaneous manifestations of cutaneous graft-versus-host disease (GVHD) or a
      precursor of GVHD. Our experience in this series emphasized that histopathologic
      evaluation is required for seemingly harmless eruptions like BHT in the
      posttransplantation period. Given the important prognostic implications of GVHD,
      physicians should be careful when confronted with BHT.

PMID- 21168746
TI  - Liver transplantation for severe hepatic graft-versus-host disease in two
      children after hematopoietic stem cell transplantation.
AB  - Chronic graft-versus-host disease (GVHD) is a frequent complication of bone
      marrow transplantation (BMT). After the skin, the liver is the second, most
      frequent target of GVHD, which presenting with hyperbilirubinemia, elevated liver
      enzymes, and coagulopathy. Progressive destruction of small intrahepatic bile
      ducts causes vanishing bile duct syndrome and leads to end-stage liver disease.
      We report 2 successful cases of orthotopic liver transplantation performed in
      children with severe GVHD after hematopoietic stem cell transplantation from a
      matched unrelated donor (HSCT-MUD).

PMID- 21168747
TI  - AFT024 cell line in co-culture system using high pore density insert (HPDI)
      maintains hematopoietic stem/progenitor cells (HSCs/HPCs) as more primitive state
      through histone modification.
AB  - BACKGROUND: It has been shown that the AFT024 stromal cell line sustains the
      engraftment capacity of human hematopoietic progenitor cells (HPCs) in vitro.
      However, the process by which AFT024 cell line maintains human HPCs is a more
      primitive state ex vivo remains unclear. METHODS: Human umbilical cord blood
      (UCB)-derived fluorescent activated cell sorter (FACS)-purified CD34(+) CD38(
      )hsc/HPCs were cultured with cytokines on hpdi (0.4 micron pore size) coated with
      irradiated AFT024 cells. The HSC/HPC and AFT024 cells contacted each other
      through 0.4 micron pores on HPDI membranes; the irradiated AFT024 cells could not
      migrate through the HPDI to contaminate the HSC/HPC. The frequency of CD34(+)Lin(
      ) cells was determined as HSCs/HPCs using flow cytometry. To evaluate their
      engraftment potential in vivo, the co-cultured cells were assayed as Long Term
      Culture-Initiating Cells (LTC-IC). To understand the process whereby AFT024 cells
      govern enhanced engraftment, we employed Western blot analysis for histone
      modifications. RESULTS: There was a 30-fold increase in frequency of CD34(+)Lin(
      ) cells in co-cultures on HPDI coated on the outer bottom surface with irradiated
      AFT024 cells and cytokines in contrast to 6-fold among controls. Total colonies
      from LTC-IC increased approximately 1.5-fold among cells cultured with AFT024,
      compared with controls. More importantly, cells co-cultured with AFT024 showed a
      more primitive state with over-methylated h3k4 (Me-H3K4), under-methylated h3k9
      (Di-Me-H3K4), and over-acetylated h4 (Ac-H4) compared with controls. CONCLUSION:
      Our results suggested that co-culture of the AFT024 cell line with HPDI
      maintained hematopoietic progenitors as a more primitive state through histone
      modification.

PMID- 21168748
TI  - Taurine supports preservation of proendocrine cell types in human umbilical cord
      blood-derived mononuclear cells during cryostorage.
AB  - BACKGROUND: We demonstrated earlier that a subset of human umbilical cord-blood
      (hUCB)-derived mononuclear cells (MNCs) express proendocrine transcription
      factors and exhibit potential to differentiate into endocrine pancreatic lineage.
      The growing interest in the use of MNCs for diabetes has promoted
      cryopreservation of these cells for future use in translational research.
      Development of optimal cryopreservation media is critical to the success of
      translational research. METHODS: We explored protective effects of taurine in
      cryopreservation of hUCB-derived MNCs. MNCs were isolated using Histopaque and 3
      million viable cells were cryofrozen using 10% dimethyl sulfoxide (v/v) in fetal
      bovine serum or supplemented with taurine (0.3/3.0 mmol/L). Cryopreservation
      conditions were assessed based on their viability, growth, and ability to retain
      endocrine pancreatic transcription factor expressing cells. RESULTS: UCB-derived
      MNCs adhered and grew as mesenchymal-like cells in culture following revival from
      various cryopreservation conditions. Interestingly, MNCs expressed threefold more
      ngn3, 2-fold more nkx6.1, and 15-fold more isl1 transcripts in taurine
      supplemented cryo-medium compared to the conventional cryomix. CONCLUSION: The
      present study demonstrates that taurine supplementation to cryopreservation media
      improved retention of endocrine pancreatic transcription factor-expressing MNCs.

PMID- 21168749
TI  - Effects of a cGMP-specific phosphodiesterase inhibitor on expression of
      endothelial nitric oxide synthase and vascular endothelial growth factor in rats
      with cyclosporine-induced nephrotoxicity.
AB  - BACKGROUND: The mechanism of cyclosporine (CsA)-induced nephrotoxicity has been
      suggested to be vasoconstriction due to reduced nitric oxide (NO), providing
      tissue fibrosis by elevation of transforming growth factor beta and vascular
      endothelial growth factor (VEGF). In this study using a rat model of CsA-induced
      nephrotoxicity, we administered a phosphodiesterase-5 inhibitor to ameliorate the
      renal injury and alter the expression of endothelial No synthase (eNOS) and VEGF.
      METHODS: A right nephrectomy was performed in Sprague-Dawley rats (n = 30; 200
      250 g, all male). The Ischemia group (n = 6) underwent ligation of the left renal
      artery for 45 minutes (IR) before observation for 28 days. After IR, the udenafil
      group (n = 6) was treated with 10 mg/kg drug orally, the CsA group (n = 6)
      received 15 mg/kg CsA injected subcutaneously and the CsA plus udenafil group (n
      = 6) received 15 mg/kg CsA injected subcutaneously together with the oral
      administration of 10 mg/kg udenafil. RESULTS: Administration of udenafil
      significantly decreased serum creatinine either alone (0.21 +/- 0.04 mg/dL) or in
      combination with CsA (1.86 +/- 0.35 mg/dL) versus the ischemia (0.85 +/- 0.22
      mg/dL) and the CsA alone (3. 10 +/- 0.77 mg/dL) group. (P = .002; P = .002).
      Comparing the Hematoxylin-eosin staining of the ischemia (0.41 +/- 0.09) and CsA
      (0.44 +/- 0.08) groups showed a significantly decreased loss of nuclei in
      proximal tubules after the administration of udenafil (0.27 +/- 0.05 [P = .004]
      and 0.26 +/- 0.02 [P = .002] respectively). Immunohistochemical staining showed
      strong eNOS staining in the udenafil and CsA plus udenafil groups. Western blots
      for eNOS showed decreased expression in the CsA group and increased expression in
      the udenafil group. Western blots for VEGF revealed reduced expression only in
      the CsA plus udenafil group. eNOS mRNA was decreased in the CsA (0.017 +/- 0.010)
      compared with the ischemia group (0.048 +/- 0.015; P = .000). VEGF mRNA which was
      decreased in the CsA group (2.026 +/- 1.109), showed greater tendency after
      administration of udenafil (0.440 +/- 0.449) (P = .003). CONCLUSION: The
      phosphodiesterase inhibitor ameliorated renal injury in a rat model of CsA
      induced nephrotoxicity, possibly related to increased eNOS and reduced VEGF
      expression.

PMID- 21168750
TI  - Transfection of hairpin small interfering RNA expression vector targeting rat
      nuclear factor (NF) (kappaB) inhibits rat cell proliferation induced by NF-kappaB
      signal pathway activation.
AB  - OBJECTIVE: The aim of this work was to construct one small interfering RNA
      (siRNA) eukaryotic expression vector targeting rat nuclear factor (NF)kappaB p65
      and identify its inhibition effect on cell proliferation according to its down
      regulation of NF-kappaB pathway. METHODS: The p65siRNA expression vector
      "pGenesil-1.2-p65siRNA" and negative control plasmid "HK" were transfected into
      the cultured rat cells. After transfection, cells were divided into 4 treatment
      groups: 1) control cells cultured in complete. Dulbecco modified Eagle medium; 2)
      lipopolysaccharide (LPS) (1 MUg/mL); (3) LPS (1 MUg/mL) + HK-transfected; 4) LPS
      (1 MUg/mL) + p65siRNA (pGenesil-1.2-p65siRNA). Thereafter, the protein levels of
      NF-kappaB p65 in the cells were detected by Western blotting at 72 hours after
      LPS stimulation. Furthermore, to observe cell proliferation, the proliferative
      rate of the cell growth was evaluated by the methylthiazolyl tetrazolium assay
      (at 24, 48, and 72 hours). The cell cycle distribution at 72 hours was detected
      by flow cytometry. RESULTS: p65siRNA effectively down-regulated the protein level
      of p65 (P < .05). Meanwhile, the proliferation of cells transfected with p65siRNA
      expression vector was significantly inhibited (P < .05), the ratio of cells at
      G(0)/G(1) stage markedly increased, and the proportion of cells at S stage was
      significantly decreased among transfected compared with control cells (P < .05).
      CONCLUSIONS: p65siRNA effectively suppressed NF-kappaB, expression, inhibiting
      rat cell proliferation induced by NF-kappaB signal pathway activation.

PMID- 21168751
TI  - Preservation of islet survival by upregulating alpha3 integrin signaling: the
      importance of 3-dimensional islet culture in basement membrane extract.
AB  - AIM: Islet transplantation is a promising treatment to cure diabetes, but is
      associated with a high rate of early graft failure. The isolation process leads
      to the loss of the surrounding extracellular matrix, resulting in eventual islet
      disintegration and apoptosis. The purpose of this study was to determine the
      effects on the viability of isolated islets of embedding islets in reconstituted
      basement membrane extract (BME), which is similar to the normal peri-islet BM
      composition in vivo. METHODS: Isolated mouse islets were embedded in BME gel for
      24 or 48 hours. Expression of caspase-3, alpha3, and alpha5, focal adhesion
      kinase (FAK), phosphor-FAK, and pancreatic duodenal homeobox factor (PDX)-1 were
      detected with Western immunoblotting. RESULTS: Impaired aggregation of single
      islet cells could only be observed in non-BME medium. Islets embedded in BME gel
      were partially protected from anoikis showed decreased caspase-3 compared with
      non-BME islets. We also observed an increase of alpha3 integrin, FAK protein
      level, and FAK activity. Furthermore, expression of PDX-1 was preserved at 48
      hours, suggesting a positive contribution of BME to beta-cell activity.
      CONCLUSION: These results indicated that embedding islets in BME can upregulate
      alpha3 integrin, which may result in preservation of viability and function of
      isolated islets.

PMID- 21168752
TI  - Administration of probiotics reduces bacterial translocation after intestinal
      transplantation in rats.
AB  - Bacterial translocation (BT) has been suggested to be responsible for the high
      incidence of infections after intestinal transplantation (IT). The purpose of
      this study was to examine whether a probiotic supplement after orthotopic IT
      ameliorated ischemia-reperfusion injury and reduced BT at 4 or 6 days
      postoperative (sham or IT), as mesenteric lymph nodes (MLNs), liver, and splenic
      tissue samples from the six groups were assessed for BT by bacterial culture,
      measurement of tumor necrosis factor-alpha (TNF-alpha) in MLNs by competitive
      reverse transcription-polymerase chain reaction, and histological evaluation by
      Park's classification. Oral administration of probiotics after IT did not improve
      short-term survival rates compared with the transplant-only groups (P > .05).
      However, the BT rates and levels of TNF-alpha in MLNs in groups with IT only were
      higher than the probiotic cohorts (P < .05). Histological injuries were
      significantly ameliorated in the group with six days of probiotic treatment
      compared with that in the nontreated hosts (P < .05). These data indicated that
      administration of probiotics after IT improved graft histology and reduced BT in
      rats.

PMID- 21168753
TI  - Inhibition of swine leukocyte antigen-I presentation in transgenic mini-pig cell
      lines by expressing human cytomegalovirus US6.
AB  - Xenotransplantation using porcine organs may resolve the chronic shortage of
      donor organs for clinical transplantation if significant immunologic barriers can
      be overcome. A xenograft can be rejected by T cells, especially CD8(+) cytotoxic
      T lymphocytes (CTL)-mediated responses, as these cells show cytotoxicity against
      xenografts by recognition of swine leukocyte antigen (SLA)-I. Peptide
      translocation is inhibited by the endoplasmic reticulum-resident human
      cytomegalovirus (HCMV) glycoprotein unique short (US) 6, due to alterations of
      the transporter associated with antigen processing loading onto MHC class I for
      antigen presentation to CD8(+) CTL. In this study we transfected the US6 gene
      into minipig fetal fibroblasts establishing three US6 clonal cell lines. Flow
      cytometry analysis of US6 clonal cell lines demonstrated a substantial reduction
      in SLA-I expression. The level of SLA-I expression in US6 clones was decreased to
      56.3% compared with the control 42.7%. In CTL assays, the rate of CD8(+) CTL
      mediated cytotoxicity was significantly reduced to 35.2% +/- 11.7% compared with
      the control, 79.9% +/- 6.5%, (P < .01). These results suggested that HCMV viral
      protein US6 suppresses the presentation of SLA-I on pig fetal fibroblast cells.
      This strategy might be used in transgenic pig production to protect porcine
      organs from CTL-mediated immune rejection.

PMID- 21168754
TI  - Nasopharyngeal T-cell monomorphic posttransplant lymphoproliferative disorders
      and combined IgA nephropathy and membranous glomerulonephritis in a patient with
      renal transplantation: a case report with literature review.
AB  - Recurrent and/or de novo glomerular diseases occurring in a renal allograft have
      been reported in the literature and are an important cause of graft dysfunction
      and eventual loss. The simultaneous occurrence of two glomerulonephritis,
      although reported in the literature, is a rare phenomenon. Posttransplant
      lymphoproliferative disorders (PTLD) are well known and one of the most serious
      and potentially fatal complications of chronic immunosuppression in the solid
      organ transplant recipient. Here, we are reporting the first case, to the best of
      our knowledge, of simultaneous occurrence of nasopharyngeal monomorphic
      monoclonal PTLD and two distinctive glomerular diseases (IgA nephropathy and
      membranous glomerulonephritis) in a 49-year-old patient who was 5 years post
      renal transplantation. We have provided the clinical history of our patient who
      presented with nephrotic range proteinuria, microscopic hematuria, and a
      nasopharyngeal mass as well as a review of the literature.

PMID- 21168755
TI  - Intractable recurrent hepatitis A virus infection requiring repeated liver
      transplantation: a case report.
AB  - Although hepatitis A virus (HAV) infection is usually self-limited, it may induce
      fulminant hepatitis. We present an unusual case of a 40-year-old, otherwise
      healthy man with intractable recurrent HAV infection requiring retransplantation
      after primary liver transplantation for HAV-associated fulminant liver failure.
      After the first living-donor liver transplantation, allograft function recovered
      uneventfully; however, beginning at 35 days, his serum total bilirubin
      concentration increased, reaching 40 mg/dL, with a slight increase in liver
      enzymes. Detection of genomic HAV RNA in serum at the time of graft dysfunction
      led to a diagnosis of recurrent HAV infection. Fifty-one days after the first
      transplant, he underwent a deceased donor retransplantation. His allograft
      function recovered; the patient was discharged from the hospital. Sixty-five days
      later, however, he was readmitted for colitis-like symptoms and was again treated
      for acute rejection, but died owing to overwhelming sepsis and persistence of HAV
      infection. These findings indicate that patients who undergo liver
      transplantation for HAV-associated liver disease may be at risk of HAV
      reinfection, particularly if they require anti-rejection therapy. Routine
      measurements of anti-HAV immunoglobulin M and HAV RNA during the early
      posttransplant period in HAV-associated liver transplant recipients may
      differentiate reinfection from an acute cellular rejection episode.

PMID- 21168756
TI  - Transcatheter aortic valve implantation in a heart transplant recipient: a case
      report.
AB  - Transcatheter aortic valve implantation (TAVI) has evolved into a feasible
      therapeutic option for the management of selected patients with severe aortic
      stenosis and high or prohibitive risk for standard surgery. Symptomatic severe
      aortic stenosis occasionally occurs in the allograft long after heart
      transplantation. Because of specific characteristics and comorbidities of heart
      transplant recipients, these patients may be considered candidates for this less
      invasive approach. We report a first case of successful transapical TAVI in a
      heart transplant recipient with symptomatic severe calcific aortic valvular
      disease and relevant comorbidities long after heart transplantation.

PMID- 21168757
TI  - Pain and smoking among cancer patients: the relationship is complex but the
      clinical implication is clear.

PMID- 21168758
TI  - Associations between pain and current smoking status among cancer patients.
AB  - There is growing empirical and clinical interest in purported associations
      between smoking and the aggravation of cancer symptoms and treatment side
      effects, such as pain. Both pain and smoking are highly prevalent among persons
      with cancer, and there is recent evidence to suggest that cancer patients who
      continue to smoke despite their diagnosis experience greater pain than
      nonsmokers. Accordingly, the main goal of this cross-sectional study was to
      examine associations between multiple levels of smoking status and several pain
      related outcomes among a sample of 224 cancer patients about to begin
      chemotherapy. Patients completed self-report measures of pain severity, pain
      related distress, and pain-related interference, as well as a demographics
      questionnaire. Results indicated that persons who continued to smoke despite
      being diagnosed with cancer reported more severe pain than never smokers, F (2,
      215)=3.47, p<.05. Current smokers also reported greater interference from pain
      than either former or never smokers, F (2, 215)=5.61, p<.01. Among former
      smokers, an inverse relation between pain severity and the number of years since
      quitting smoking was observed, r (104)=-.26, p<.01. These data suggest that
      continued smoking despite a cancer diagnosis is associated with greater pain
      severity and interference from pain; however, future research is warranted to
      determine the directionality of this relationship.

PMID- 21168759
TI  - Engineered thrombin aims to take on heparin.

PMID- 21168760
TI  - A novel enzymatic rearrangement.
AB  - Human Fe(II)-alpha-ketoglutarate-dependent dioxygenases are a diverse enzyme
      family involved in a number of biological processes, from collagen biosynthesis
      to transcription. In this issue, Leung et al. (2010) add a new reaction to their
      ever-expanding catalytic repertoire.

PMID- 21168761
TI  - Nucleosomes and cisplatin.
AB  - In order to form a covalent complex with DNA inside human cells, cisplatin has to
      overcome the protective environment of a nucleosome, where DNA is complexed with
      histone proteins. Todd and Lippard (2010) expand our understanding of this
      process by describing the structure of a nucleosome containing a Pt-DNA adduct,
      which has important implications for more effective chemotherapeutic drug
      development.

PMID- 21168762
TI  - Epigenetics gets sweeter: O-GlcNAc joins the "histone code".
AB  - O-GlcNAcylation has now been added to the growing list of histone modifications
      making up the multifaceted "histone-code" (Sakabe et al., 2010). The sites of O
      GlcNAc-histone modification hint at a role in chromatin remodeling, thus adding
      to mounting evidence that O-GlcNAc cycling sits atop a robust regulatory network
      maintaining higher-order chromatin structure and epigenetic memory.

PMID- 21168763
TI  - Natural product-guided discovery of a fungal chitinase inhibitor.
AB  - Natural products are often large, synthetically intractable molecules, yet
      frequently offer surprising inroads into previously unexplored chemical space for
      enzyme inhibitors. Argifin is a cyclic pentapeptide that was originally isolated
      as a fungal natural product. It competitively inhibits family 18 chitinases by
      mimicking the chitooligosaccharide substrate of these enzymes. Interestingly,
      argifin is a nanomolar inhibitor of the bacterial-type subfamily of fungal
      chitinases that possess an extensive chitin-binding groove, but does not inhibit
      the much smaller, plant-type enzymes from the same family that are involved in
      fungal cell division and are thought to be potential drug targets. Here we show
      that a small, highly efficient, argifin-derived, nine-atom fragment is a
      micromolar inhibitor of the plant-type chitinase ChiA1 from the opportunistic
      pathogen Aspergillus fumigatus. Evaluation of the binding mode with the first
      crystal structure of an A. fumigatus plant-type chitinase reveals that the
      compound binds the catalytic machinery in the same manner as observed for argifin
      with the bacterial-type chitinases. The structure of the complex was used to
      guide synthesis of derivatives to explore a pocket near the catalytic machinery.
      This work provides synthetically tractable plant-type family 18 chitinase
      inhibitors from the repurposing of a natural product.

PMID- 21168764
TI  - BTZO-1, a cardioprotective agent, reveals that macrophage migration inhibitory
      factor regulates ARE-mediated gene expression.
AB  - In a screening program to discover therapeutic drugs for heart diseases, we
      identified BTZO-1, a 1,3-benzothiazin-4-one derivative, which activated
      antioxidant response element (ARE)-mediated gene expression and suppressed
      oxidative stress-induced cardiomyocyte apoptosis in vitro. An active BTZO-1
      derivative for ARE-activation protected heart tissue during ischemia/reperfusion
      injury in rats. Macrophage migration inhibitory factor (MIF), which is known to
      protect cells from oxidative insult, was identified as a specific BTZO-1-binding
      protein. BTZO-1 binds to MIF with a K(d) of 68.6 nM, and its binding required the
      intact N-terminal Pro1. MIF, in the presence of BTZO-1, activated the glutathione
      S-transferase Ya subunit (GST Ya) gene ARE, whereas reduction of cellular MIF
      protein levels by siRNA suppressed BTZO-1-induced GST Ya expression. These
      results suggest that BTZO-1 activates the GST Ya gene ARE by interacting with
      MIF.

PMID- 21168765
TI  - The CYPome of Sorangium cellulosum So ce56 and identification of CYP109D1 as a
      new fatty acid hydroxylase.
AB  - The first systematic study of the complete cytochrome P450 complement (CYPome) of
      Sorangium cellulosum So ce56, which is a producer of important secondary
      metabolites and has the largest bacterial genome sequenced to date, is presented.
      We describe the bioinformatic analysis of the So ce56 cytochrome P450 complement
      consisting of 21 putative P450 genes. Because fatty acids play a pivotal role
      during the complex life cycle of myxobacteria, we focused our studies on the
      characterization of fatty acid hydroxylases. Three novel potential fatty acid
      hydroxylases (CYP109D1, CYP264A1, and CYP266A1) were used for detailed
      characterization. One of them, CYP109D1 was able to perform subterminal
      hydroxylation of saturated fatty acids with the support of two autologous and one
      heterologous electron transfer system(s). The kinetic parameters for the product
      hydroxylation were derived.

PMID- 21168766
TI  - Engineering enzyme specificity using computational design of a defined-sequence
      library.
AB  - Engineered biosynthetic pathways have the potential to produce high-value
      molecules from inexpensive feedstocks, but a key limitation is engineering
      enzymes with high activity and specificity for new reactions. Here, we developed
      a method for combining structure-based computational protein design with library
      based enzyme screening, in which inter-residue correlations favored by the design
      are encoded into a defined-sequence library. We validated this approach by
      engineering a glucose 6-oxidase enzyme for use in a proposed pathway to convert D
      glucose into D-glucaric acid. The most active variant, identified after only one
      round of diversification and screening of only 10,000 wells, is approximately 400
      fold more active on glucose than is the wild-type enzyme. We anticipate that this
      strategy will be broadly applicable to the discovery of new enzymes for
      engineered biological pathways.

PMID- 21168767
TI  - Structural and mechanistic studies on gamma-butyrobetaine hydroxylase.
AB  - The final step in carnitine biosynthesis is catalyzed by gamma-butyrobetaine
      (gammaBB) hydroxylase (BBOX), an iron/2-oxoglutarate (2OG) dependent oxygenase.
      BBOX is inhibited by trimethylhydrazine-propionate (THP), a clinically used
      compound. We report structural and mechanistic studies on BBOX and its reaction
      with THP. Crystallographic and sequence analyses reveal that BBOX and
      trimethyllysine hydroxylase form a subfamily of 2OG oxygenases that dimerize
      using an N-terminal domain. The crystal structure reveals the active site is
      enclosed and how THP competes with gammaBB. THP is a substrate giving
      formaldehyde (supporting structural links with histone demethylases),
      dimethylamine, malonic acid semi-aldehyde, and an unexpected product with an
      additional carbon-carbon bond resulting from N-demethylation coupled to oxidative
      rearrangement, likely via an unusual radical mechanism. The results provide a
      basis for development of improved BBOX inhibitors and may inspire the discovery
      of additional rearrangement reactions.

PMID- 21168768
TI  - Photoreactive stapled BH3 peptides to dissect the BCL-2 family interactome.
AB  - Defining protein interactions forms the basis for discovery of biological
      pathways, disease mechanisms, and opportunities for therapeutic intervention. To
      harness the robust binding affinity and selectivity of structured peptides for
      interactome discovery, we engineered photoreactive stapled BH3 peptide helices
      that covalently capture their physiologic BCL-2 family targets. The crosslinking
      alpha helices covalently trap both static and dynamic protein interactors, and
      enable rapid identification of interaction sites, providing a critical link
      between interactome discovery and targeted drug design.

PMID- 21168769
TI  - Consequences of cisplatin binding on nucleosome structure and dynamics.
AB  - The effects of cisplatin binding to DNA were explored at the nucleosome level to
      incorporate key features of the eukaryotic nuclear environment. An X-ray crystal
      structure of a site-specifically platinated nucleosome carrying a 1,3-cis
      {Pt(NH3)2}2+-d(GpTpG) intrastrand cross-link reveals the details of how this
      adduct dictates the rotational positioning of DNA in the nucleosome. Results from
      in vitro nucleosome mobility assays indicate that a single platinum adduct
      interferes with ATP-independent sliding of DNA around the octamer core. Data from
      in vitro transcription experiments suggest that RNA polymerases can successfully
      navigate along cisplatin-damaged DNA templates that contain nucleosomes, but
      stall when the transcription elongation complex physically contacts a platinum
      cross-link located on the template strand. These results provide information
      about the effects of cisplatin binding to nuclear DNA and enhance our
      understanding of the mechanism of transcription inhibition by platinum anticancer
      compounds.

PMID- 21168770
TI  - Activation of LDL receptor expression by small RNAs complementary to a noncoding
      transcript that overlaps the LDLR promoter.
AB  - Low-density lipoprotein receptor (LDLR) is a cell-surface receptor that plays a
      central role in regulating cholesterol levels. Increased levels of LDLR would
      lead to reduced cholesterol levels and contribute to strategies designed to treat
      hypercholesterolemia. We have previously shown that duplex RNAs complementary to
      transcription start sites can associate with noncoding transcripts and activate
      gene expression. Here we show that duplex RNAs complementary to the promoter of
      LDLR activate expression of LDLR and increase the display of LDLR on the surface
      of liver cells. Activation requires complementarity to the LDLR promoter and can
      be achieved by chemically modified duplex RNAs. Promoter-targeted duplex RNAs can
      overcome repression of LDLR expression by 25-hydroxycholesterol and do not
      interfere with activation of LDLR expression by lovastatin. These data
      demonstrate that small RNAs can activate LDLR expression and affect LDLR
      function.

PMID- 21168772
TI  - The easy virtue of CD1c.

PMID- 21168771
TI  - Synthetic UDP-furanoses as potent inhibitors of mycobacterial galactan
      biogenesis.
AB  - UDP-galactofuranose (UDP-Galf) is a substrate for two types of enzymes, UDP
      galactopyranose mutase and galactofuranosyltransferases, which are present in
      many pathogenic organisms but absent from mammals. In particular, these enzymes
      are involved in the biosynthesis of cell wall galactan, a polymer essential for
      the survival of the causative agent of tuberculosis, Mycobacterium tuberculosis.
      We describe here the synthesis of derivatives of UDP-Galf modified at C-5 and C-6
      using a chemoenzymatic route. In cell-free assays, these compounds prevented the
      formation of mycobacterial galactan, via the production of short "dead-end"
      intermediates resulting from their incorporation into the growing oligosaccharide
      chain. Modified UDP-furanoses thus constitute novel probes for the study of the
      two classes of enzymes involved in mycobacterial galactan assembly, and studies
      with these compounds may ultimately facilitate the future development of new
      therapeutic agents against tuberculosis.

PMID- 21168773
TI  - CuRTAiling interferon regulatory factor signaling with the E3 ligase RAUL.

PMID- 21168774
TI  - Foxo1 and Foxo3 help Foxp3.

PMID- 21168775
TI  - Treg's alter ego: an accessory in tumor killing.

PMID- 21168776
TI  - Does deleting dendritic cells delete autoimmunity?

PMID- 21168779
TI  - Envenomation by the scorpion Tityus breweri in the Guayana Shield, Venezuela:
      report of a case, efficacy and reactivity of antivenom, and proposal for a
      toxinological partitioning of the Venezuelan scorpion fauna.
AB  - OBJECTIVES: Scorpion envenomation is a common public health problem in Venezuela.
      We report an envenoming case by Tityus breweri, endemic to the Guayana Shield,
      southeast Venezuela, and the outcome of its treatment with antivenom anti-Tityus
      discrepans. Toxin composition and antigenic reactivity of T breweri venom were
      also explored. T breweri distribution range was re-evaluated. METHODS: Clinical
      signs and symptoms in an adult male were recorded after envenoming and treatment
      with antivenom. Toxin composition and antigenicity of T breweri venom were
      investigated by polyacrylamide gel electrophoresis, immunoblotting, and mass
      spectrometry. T breweri distribution range was reassessed by mapping new records
      of the species. RESULTS: The moderately severe case (a 21-year-old man) presented
      autonomic manifestations, including cardiopulmonary and gastrointestinal effects.
      Full recovery was achieved after anti-T discrepans antivenom administration. T
      breweri venom contains toxins in the 6-8 kd range that affect voltage-sensitive
      sodium channels. Based on new records, T breweri distribution area reaches 12 155
      km.(2) Inclusion of southeast Venezuela as an endemic area of scorpionism
      prompted the examination of clinical, immunological, and phylogenetic evidence
      for suggesting a partitioning of the Venezuelan Tityus fauna into toxinological
      provinces. CONCLUSIONS: The severity of the case reinforces categorization of the
      Guayana Shield region as a macroendemic area of scorpionism in Venezuela and
      allows classification of T breweri as a species of medical importance, with
      toxins immunologically related to central-eastern Venezuelan Tityus. Partitioning
      of the territory incorporating multiple criteria may help health authorities
      establish and implement preventive and therapeutic measures for scorpion
      envenoming in this region.

PMID- 21168780
TI  - Sailing injury and illness: results of an online survey.
AB  - OBJECTIVE: The purpose of this study was to describe the relative frequency,
      patterns, and mechanisms of sailing-related injuries in dinghies and keelboats.
      Data were also collected on risky and risk-averse behaviors of sailors, as well
      as on sailing-related illnesses. METHODS: A web-based, logic-driven, multiple
      choice survey was developed and links were posted on sailing-related websites.
      Data were collected from March through November 2006 on any injuries or illnesses
      sailors sustained over the prior 12 months. RESULTS: From 1188 respondents, a
      total of 1715 injuries and 559 illnesses was reported. The top 3 injuries for
      keel boats were leg contusions (11%), hand lacerations (8%), and arm contusions
      (6%), and in dinghies they were leg contusions (13%), knee contusions (6%), and
      leg lacerations (6%). The most common mechanisms of injury were "trip/fall," "hit
      by object," and "caught in lines." Tacking, heavy weather, and jibing were the
      most common factors contributing to injury. The rates of injury and severe injury
      in this internet-based survey were 4.6 and 0.57 per 1000 days of sailing,
      respectively. Of the 70 severe injuries, 25% were fractures, 16% were torn
      tendons or cartilage, 14% were concussions, and 8% were dislocations. The median
      rate of lifejacket use was 30%, and median rate of sunscreen use was 80%. Sixteen
      percent of sailors reported sunburn over the prior 12 months. Seven percent of
      sailors reported use of alcohol within the 2 hours preceding injury. CONCLUSIONS:
      The most common injuries in both keel boats and dinghies are soft-tissue injuries
      to the extremities. Severe injuries and illnesses in sailing are uncommon in this
      study population.

PMID- 21168777
TI  - Ubiquitin makes its mark on immune regulation.
AB  - Ubiquitination, the covalent attachment of ubiquitin molecules to proteins, is
      emerging as a widely utilized mechanism for rapidly regulating cell signaling.
      Recent studies indicate that ubiquitination plays potent roles in regulating a
      variety of signals in both innate and adaptive immune cells. Here, we will review
      recent studies of ubiquitin ligases, ubiquitin chain linkages, and ubiquitin
      binding proteins that highlight the diversity and specificity of ubiquitin
      dependent functions in immune cells. We will also review studies that shed light
      on how ubiquitination signals are integrated in cell-type-specific fashion to
      regulate the immune system in vivo.

PMID- 21168781
TI  - Accuracy of internet recommendations for prehospital care of venomous snake
      bites.
AB  - OBJECTIVE: To evaluate the accuracy of Internet information regarding the
      prehospital care of venomous snake bites. METHODS: Two major search engines were
      used to identify 48 Web sites regarding 6 prehospital treatment options for snake
      bite (removal of constrictive devices, ice, heat, electric shock, incision, and
      suction). Web sites were evaluated for their quality using the Health on the Net
      (HON) seal and Journal of the American Medical Association (JAMA) benchmarks.
      RESULTS: Of the 48 Web sites reviewed, 26 (54.1%) contained inappropriate
      recommendations. The remaining 22 Web sites were appropriate regarding all
      modalities addressed. Among the Web sites reviewed, inappropriate treatment
      recommendations included: suction (14); ice (6); incision (4); electric shock
      (1). Five Web sites that met all 4 JAMA benchmarks and the HON seal included 3
      inappropriate treatment recommendations. Conversely, the 5 Web sites that met
      none of the JAMA benchmarks nor included the HON seal included only 2
      inappropriate treatment measures. CONCLUSION: This study highlights the variety
      of misinformation available on the Internet regarding prehospital care of snake
      bites, and the unreliability of the HON seal and JAMA benchmarks as markers of
      accuracy. As the Internet becomes an increasing source of medical information for
      both the public and clinicians, the importance of accurate Web sites becomes
      imperative. Clinicians and lay people should be aware of the high variability of
      Internet information regarding snake bite prehospital care.

PMID- 21168782
TI  - Rhabdomyolysis and hyponatremia: a cluster of five cases at the 161-km 2009
      Western States Endurance Run.
AB  - OBJECTIVE: Five of 400 starters of the 2009 Western States Endurance Run (WSER)
      were hospitalized with hyponatremia and rhabdomyolysis. This article explores the
      risk factors associated with development of hyponatremia and rhabdomyolysis.
      METHODS: Data on the 5 cases were collected retrospectively from the runners and
      medical records, and all race participants were invited to complete a post-race
      survey. Characteristics of the cases were compared with the other race
      participants. RESULTS: The 5 runners developing hyponatremia with rhabdomyolysis
      were men with a mean (+/-SD) age of 39 +/- 7 years. Presenting complaints
      included neurological symptoms among 3 and nausea among 3. Compared with those
      runners not developing hyponatremia with rhabdomyolysis, the cases tended to be
      younger, faster, more likely to have sustained an injury which interfered with
      training prior to the race, and were more likely to use nonsteroidal anti
      inflammatory drugs (NSAIDs) during the race. The 3 of 5 cases progressing to
      acute renal failure were characterized by higher initial blood urea nitrogen
      (BUN; 43-69 vs 18-23 mg/dL) and creatinine (2.8-4.9 vs 1.1-1.2 mg/dL) levels but
      were not distinguished by creatinine phosphokinase (CPK) concentrations.
      CONCLUSIONS: Over 1% of participants in the 2009 WSER were hospitalized with
      hyponatremia in combination with rhabdomyolysis. These individuals tended to be
      younger, faster, more likely to have had an injury that interfered with training,
      and more likely to have used NSAIDs during the race. Higher initial BUN and
      creatinine levels, but not CPK concentrations, distinguished those 3 who
      progressed to acute renal failure.

PMID- 21168783
TI  - Postexercise peripheral oxygen saturation after completion of the 6-minute walk
      test predicts successfully reaching the summit of Aconcagua.
AB  - OBJECTIVE: The 6-minute walk test (6MWT) is a single measurement of functional
      status in patients with cardiovascular disease. It has not been studied at high
      altitude. We investigate the screening value of 6-minute walk distance (6MWD) and
      postexercise vital sign (VS) measurements as predictors of successfully reaching
      the summit or development of acute mountain sickness (AMS) on Aconcagua (6962 m).
      METHODS: Prospective observational cohort in Aconcagua Provincial Park,
      Argentina. Adults climbing the normal route who registered with base camp
      physicians were included. There were no exclusion criteria. VSs were measured
      before (resting) and after (postexercise) completion of 6MWT while volunteers
      acclimatized at Plaza de Mulas base camp (4365 m). Volunteers proceeded towards
      the summit at their own pace and upon descent returned a questionnaire with
      maximum altitude reached and Lake Louise AMS Self-report Score (LLSelf). RESULTS:
      One hundred twenty-four volunteers completed the 6MWT. Sixty-four volunteers
      (51.6%) completed questionnaires; 56% summited. Median LLSelf was 4 (IQR: 3.0
      6.5). There was no association between any resting or postexercise VS
      measurements and AMS. However, mean postexercise SpO(2) was 80.8% in summiters
      and 76.4% in nonsummiters, a difference of -4.4% (95% CI: -6.7 to -2.0, p =
      0.0005). Postexercise SpO(2) < 75% had 97.2% sensitivity and negative likelihood
      ratio of 0.086 in predicting the outcome of successfully reaching the summit:
      only one climber with SpO(2) < 75% successfully reached the summit. CONCLUSIONS:
      This study provides the first published data on 6MWD recorded in the field at
      high altitude. Postexercise SpO(2) < 75% may be a useful screening test for
      predicting the outcome of successfully reaching the summit of Aconcagua.

PMID- 21168784
TI  - Expedition medicine--the risk of illness and injury.
AB  - OBJECTIVE: Expeditions organized by commercial companies are becoming
      increasingly popular. Charity expeditions take inexperienced participants on
      trips all over the world, with participants being sponsored to raise funds for
      charitable causes. The incidence of illness or injury while participating in
      charity expeditions is unknown. The objective of this study is to report the
      incidence and severity of illness and injuries occurring on worldwide charity
      expeditions. METHODS: Retrospective, observational study reviewing expedition
      medical reports from 232 expeditions organized by a single commercial expedition
      company for a 5-year period (January 1, 2004 through December 31, 2008). RESULTS:
      Complete expedition medical reports were available for 210 (91%) trips, involving
      4077 participants over 1524 expedition days. Expeditions reported a total of 1564
      incidents over 42482 participant-days in the field, including days spent
      traveling to the expedition site. In 1465 (94%) cases "minor" injury or illness
      was recorded, 79 (5%) "moderate," and 20 (1%) "major" in severity. No deaths were
      reported. Gastrointestinal upset was the commonest reported minor condition and
      severe acute mountain sickness the commonest major condition. Overall, the
      incidence per 1000 participant-days of minor illness or injury was 34.48,
      moderate illness or injury 1.86, and major illness or injury 0.47. CONCLUSION:
      The risk of sustaining major injury or illness on an overseas charity expedition
      is low. The consequences of becoming injured or unwell in a remote environment
      can be serious, and appropriate medical care is required.

PMID- 21168785
TI  - Oxidative stress status in rats after intermittent exposure to hypobaric hypoxia.
AB  - OBJECTIVE: Programs of intermittent hypobaric hypoxia (IHH) exposure are used to
      raise hemoglobin concentration and erythrocyte mass. Although acclimation
      response increases blood oxygen transport capacity leading to a VO(2max)
      increase, the effects of reactive oxygen species (ROS) might determine the
      behavior of erythrocytes and plasma, thus causing a worse peripheral blood flow.
      The goals of the study were to establish the hematological changes and to discern
      whether an IHH protocol modifies the antioxidant/pro-oxidant balance in
      laboratory rats. METHODS: Male rats were subjected to an IHH program consisting
      of a daily 4-hour session for 5 days/week until completing 22 days of hypoxia
      exposure in a hypobaric chamber at a simulated altitude of 5000 m. Blood samples
      were taken at the end of the exposure period (H) and at 20 (P20) and 40 (P40)
      days after the end of the program, and compared to control (C), maintained at sea
      level pressure. Hematological parameters were measured together with several
      oxidative stress indicators: plasma thiobarbituric acid reactive substances
      (TBARS) and erythrocyte catalase (CAT) and superoxide dismutase (SOD). RESULTS:
      Red blood cell (RBC) count, hemoglobin concentration and hematocrit were higher
      in H group as compared to all the other groups (p < 0.001). However, there were
      no significant differences between the 4 groups in any of the oxidative stress
      related parameters. CONCLUSIONS: The absence of significant differences between
      groups indicates that our IHH program has little impact on the general redox
      status, even in the laboratory rat, which is more sensitive to hypoxia than
      humans. We conclude that IHH does not increase oxidative stress.

PMID- 21168786
TI  - 10% Povidone-iodine may be a practical field water disinfectant.
AB  - OBJECTIVE: A paucity of data exists regarding the use of iodophores such as
      povidone-iodine (PVI) to disinfect water. We sought to determine a practical
      minimal disinfecting concentration of 10% PVI over different contact times and
      temperatures when added to water inoculated with E. coli. METHODS: 1:100,
      1:1,000, and 1:10,000 dilutions of 10% PVI were created. Escherichia coli was
      exposed to these dilutions for 5, 15, and 30 minutes at 10, 20, and 30 degrees C.
      Bactericidal activity was neutralized with 0.5% sodium thiosulfate. Mean viable
      colony forming units (CFUs) was determined after triplicate plating on Luria
      bertani agar and 24 hours of incubation at 37 degrees C. Effective bactericidal
      activity was defined as a 5-log reduction. RESULTS: Of the 200,000 E. coli
      plated, no CFUs were observed after exposure to the 1:100 dilution. After 5
      minutes of contact time with the 1:1,000 dilution, at 10 degrees C CFUs were too
      numerous to count (TNTC), at 20 degrees C the mean CFU count was 92 (standard
      error +/-11), and at 30 degrees C the mean CFU count was 25 (standard error +/
      8). No CFUs were observed after 15 minutes of exposure to the 1:1,000 dilution
      across experimental temperatures. The 1:10,000 dilution always yielded CFU growth
      that was TNTC. CONCLUSIONS: The lowest disinfecting concentration of 10% PVI was
      the 1:1,000 dilution at 15 minutes of contact time. This supports the use of PVI
      for water disinfection against E. coli, the organism most commonly responsible
      for traveler's diarrhea. Further studies may assess its effectiveness against
      more virulent water borne pathogens.

PMID- 21168787
TI  - Mental health response to acute stress following wilderness disaster.
AB  - Expedition physicians should be prepared to respond to traumatic stress disorders
      following wilderness disasters. Stress disorder symptoms include re-experiencing
      the traumatic event, avoiding stimuli associated with the traumatic event, and
      increased physical arousal. These symptoms can also be seen in healthy
      individuals, and should only lead to disorder diagnosis when they cause distress
      or impairment. Treatment options for stress disorders include observation,
      psychological interventions, and medication. Approximately half of those with
      diagnosable stress disorders will return to nondiagnosable status over time
      without therapeutic intervention. Psychological interventions with empirical
      support concentrate on providing either noninvasive support in the short term,
      such as psychological first aid (PFA), or more long-term controlled re
      experiencing of the precipitating trauma, such as many exposure-based therapies.
      Exposure-based treatments can result in temporary increases in symptoms before
      long-term gains are realized, so they are not recommended for wilderness
      settings. Medications to treat stress disorders include benzodiazepines,
      propranolol, and antidepressant medications. Benzodiazepines are often carried in
      wilderness first aid kits, but they provide very limited stress disorder symptom
      relief. Propranolol is being explored as a method of preventing traumatic stress
      disorders, but the data are not currently conclusive. Antidepressant medications
      are a good long-term strategy for stress disorder treatment, but they are of
      limited utility in wilderness settings as they are unlikely to be included in
      expedition medical kits and require approximately 4 weeks of administration for
      symptom reduction. Recommendations for wilderness treatment of stress disorders
      focus on increasing knowledge of stress disorder diagnosis and PFA.

PMID- 21168788
TI  - Complications of steroid use on Mt. Everest.
AB  - Steroids are used for the prevention and treatment of high-altitude illnesses.
      However, these agents can cause significant side effects. We report a case of
      altered mental status, gastrointestinal bleeding, skin rash, and avascular
      necrosis in a climber taking prophylactic dexamethasone prior to an attempt to
      climb Mt Everest. High-altitude cerebral edema (HACE), steroid toxicity, and
      acute adrenal crisis can have similar clinical presentations. Differentiating
      between these life-threatening conditions at high altitude is essential for
      successful treatment.

PMID- 21168789
TI  - Coati (Nasua nasua) attacks on humans: case report.
AB  - Coatis [including Nasua nasua, the ring-tailed coati], are medium-sized mammals
      widely distributed in the Americas. They are social animals, whose normal diet
      includes insects, fruits, and small vertebrates, and rarely prey on larger sized
      animals. There are, to our knowledge, no reports in the medical literature of
      attacks on humans. This report describes a coati attack on 2 children in their
      home. The children sustained deep scratches and bites. The animal may have
      injured the humans in a defensive strike, but motivation for attack was
      uncertain. Coati attacks may occur in places where there is interaction between
      these mammals and humans.

PMID- 21168790
TI  - Is the Puerto Rican racer, Alsophis portoricensis, really harmless? A case report
      series.
AB  - Puerto Rico (PR) is home to 10 indigenous species of snake. Alsophis
      portorricensis has traditionally been considered harmless. In 1961, Hageman
      classified A portorricensis as somewhere between "venomous" and "nonvenomous." In
      1966, Heatwole and Banuchi reported the only case found in the literature of a
      "venomous" bite from Alsophis portorricensis. Only 6 cases of snakebite were
      reported to the PR Department of Health from 1998 to 2007; ecchymosis, swelling,
      and abnormal vital signs were noted in all of the cases. In 5 of these 6 cases,
      the captured snake was, in fact, identified as Alsophis portorricensis of the
      Colubridae family; in the remaining case, the description strongly suggests that
      it was the same species as the others. All bites were inflicted on fingers, which
      were presented for evaluation from 2 to 24 hours after the event. All documented
      cases report that the bite lasted from 1 to 4 minutes. All of the victims
      presented with localized pain and ecchymosis. Localized edema extended from the
      hand to the elbow in 4 cases, and up to the shoulder in 2 cases. All patients
      were treated symptomatically, observed at the Emergency Department (ED), and
      discharged home within 24 hours after the ED evaluation. All patients reported
      the resolution of symptoms within 1 week. Traditionally, PR has not been
      associated with any dangerous species of snake. These cases show that the second
      most abundant snake on the island can inflict a venomous bite, with local and
      systemic symptoms that warrant adequate preparation by the medical community.

PMID- 21168791
TI  - Safety and efficacy of attempts to reduce shoulder dislocations by non-medical
      personnel in the wilderness setting.
AB  - OBJECTIVE: The objectives of this study were to explore the success rate and the
      complication rate for shoulder reduction attempts by non-medical personnel in the
      wilderness setting, and to compare the average time to reduction for those done
      on scene versus those that waited for reduction at a medical facility. METHODS:
      In this study we solicited online survey responses from users of wilderness
      sports forums between October 2008 and April 2009. These surveys asked
      respondents to describe previous wilderness sports injuries they experienced.
      Descriptive statistics were calculated, and the Mann-Whitney U test was used to
      compare average reduction times, with an alpha of .05 selected as the
      significance threshold. RESULTS: Overall, there were 112 responses with 56
      describing shoulder dislocations that were reduced either on scene or at a
      medical facility. Reduction on scene, in the absence of a medically trained
      person, was attempted in 39 of these 56 cases with a success rate of 71.8%
      (28/39). The median time to reduction on scene was 5 minutes, compared to 135
      minutes from the time of injury for those that were reduced at a medical facility
      (P <.001). Other than pain during the reduction, there were no reports of serious
      complications associated with the reduction attempts. CONCLUSIONS: These data
      suggest that reduction of dislocations in the wilderness setting by non-medical
      personnel may be safe and effective, and significantly decreases the time to
      reduction. These findings may help guide future instruction of participants in
      high-risk wilderness sports.

PMID- 21168792
TI  - Introduction to 'Injuries and illness in college outdoor education'.

PMID- 21168793
TI  - Injury and illness in college outdoor education.
AB  - OBJECTIVE: Many colleges offer outdoor education courses such as rock climbing,
      kayaking, and mountain biking. Since these sports may be perceived as dangerous,
      we describe the prevalence of injuries and illnesses in a large, university-based
      outdoor education program. We also compare composite incident rates from this
      outdoor program to those of traditional college sports. METHODS: Cohort of
      college students participating in either Cornell Outdoor Education (COE) or
      National Collegiate Athletic Association (NCAA) sports and comparison of incident
      rates. COE data were prospectively collected in the field; and NCAA data were
      prospectively collected through the Association's Injury Surveillance System. By
      definition, a COE injury or illness required follow-up care, prescription
      medication, or limited course participation. Similarly, a NCAA injury limited
      further practice or play. Incident rates were calculated as injuries and
      illnesses per 1000 participant-days (COE) or injuries per 1000 athlete-exposures
      (NCAA). RESULTS: Included COE courses during 2002-2007 totaled 74 005 participant
      days. There were 111 injuries and illnesses, rate = 1.50/1000 participant-days
      (95% CI 1.24-1.81). The NCAA reported 32 646 899 athlete-exposures during 1988
      2004 and 181 476 injuries, rate = 5.56/1000 athlete-exposures (95% CI 5.53-5.58).
      Compared to COE, the relative risk of injury in NCAA sports was 3.7 (95% CI 3.1
      4.5) overall and 3.3 (95% CI 2.8-4.0) after excluding the high-contact sports of
      football, ice hockey, and wrestling. For COE, mountain biking had the highest
      incident rate (7.5/1000), which was significantly lower than game injury rates in
      NCAA football and soccer. The most common injuries for both NCAA and COE were
      soft-tissue injuries such as sprains and strains. CONCLUSION: Outdoor education
      at this university-sponsored program was at least as safe as traditional college
      sports. Overall, college students were less likely to be injured while
      participating in COE courses than while participating in NCAA sports, even after
      excluding high-contact sports from the comparison.

PMID- 21168794
TI  - First aid and public access defibrillation in mountain huts: the Mountain Huts
      Initiative of the Bergamo section of the Club Alpino Italiano.

PMID- 21168795
TI  - In response to "Wilderness first aid and the law".

PMID- 21168796
TI  - Wilderness Medical Society consensus guidelines for the prevention and treatment
      of acute altitude illness--a view from the other side of the Atlantic.

PMID- 21168797
TI  - Extremely late presentation of catfish spine injury to the hand.

PMID- 21168799
TI  - Improvements in identification of the best sperm for ICSI?

PMID- 21168800
TI  - The myth and reality of disability prevalence: measuring disability for research
      and service.
AB  - The concept of disability has medical, functional, and social components. We
      review the frameworks for the definition of disability and endorse a
      multidimensional approach that is parsimonious and has utility for epidemiology.
      We need to be able to count people with disabilities to quantify service and
      support needs, to study the life course of people with specific disabilities, and
      to accurately target prevention strategies. In addition, it is important to have
      some precise measures of disability so comparisons can be made between
      impairments, to identify disparities and differences, and to measure changes over
      time. We need to ensure that there is no confusion about cause and effect
      (attributing associated conditions as outcomes of disability when they are in
      fact the cause of the functional limitation) and that comparisons to people
      without disabilities are fair. If people who experience disability due to a
      condition such as obesity are included in the case definition of disability, then
      we cannot say people with disability are more likely to be obese. The credibility
      of disability epidemiology and the disability field is at stake.

PMID- 21168801
TI  - Building a future in disability and public health.
AB  - The Disability Section is one of the newest sections in the American Public
      Health Association (APHA) and represents people with disabilities as an
      underserved population in all areas of public health practice. Issues involving
      people with disabilities cut across the overarching domains of education,
      training, research, and service. Therefore, every constituency group, interest
      area, or section in the APHA must recognize the importance of addressing
      disability-related issues in any initiative that focuses on improving the health
      of our nation. While achieving section status within APHA has given "disability"
      increased visibility in the largest and most prominent public health organization
      in the world, focusing our future on infusing disability content and perspectives
      on issues that impact people with disabilities in other areas of public health
      (e.g., environment, gerontological health, medical care, public health education
      and health promotion, etc.) requires an understanding of the other side's
      perspective. For this to occur, the Disability Section must be used as a base for
      recruiting and deploying health professionals who have an interest in a dyadic
      area of public health (e.g., medical care and disability, gerontological health
      and aging with a disability), and who can begin serving in leadership positions
      in other sections in APHA. Building capacity within and across the other sections
      in APHA will be our greatest challenge over these next few years. Our journey has
      just begun.

PMID- 21168802
TI  - Evolving views of disability and public health: the roles of advocacy and public
      health.
AB  - Promoting health, quality of life, and participation of persons with disabilities
      is a relatively recent development in public health. Its brief history reflects
      three distinct public health perspectives toward disability-a traditional
      approach that focuses on preventing disability, a contemporary approach that
      regards disability as a minority group experiencing disparities relative to
      people without disabilities, and an emerging perspective where disability status
      is considered one of multiple determinants of health. The field of disability and
      health has been influenced by the interaction of disability advocacy with the
      public health process of surveillance, epidemiology research, and intervention.
      Advocacy draws on political and legal arguments to press for action on issues
      such as health care access, control of services, and choice of residence. Public
      health uses surveillance to document magnitude of problems; epidemiology to
      identify specific groups, develop measures, and apply rigorous research methods;
      and intervention to improve health behaviors and health outcomes. The field of
      disability and public health, however, has lagged in addressing the role of
      environmental factors in the disabling process, in moving to societal
      participation as an outcome, and in implementing population scale interventions.

PMID- 21168803
TI  - Disability and health behavior change.
AB  - OBJECTIVE/HYPOTHESIS: We conducted a review of four health behavior change (HBC)
      theories (Health Belief, Theory of Planned Behavior, Social Cognitive, and
      Transtheoretical) to consider how these theories conceptually apply to people
      with disabilities. METHODS: We identified five common constructs across HBC
      theories and examined how these commonalities fit within the International
      Classification of Function (ICF). RESULTS: Four of the HBC constructs appear to
      be Personal Factors within the ICF, while the fifth represents Environmental
      Factors. CONCLUSIONS: Using the ICF framework to understand disability and HBC,
      we propose that including a sense of meaning as another personal factor will
      further develop HBC theories that lead to more effective HBC interventions for
      people with disabilities.

PMID- 21168804
TI  - History at the intersection of disability and public health: the case of John
      Galsworthy and disabled soldiers of the First World War.
AB  - The author presented an earlier version of this historical article to the
      Disability Section of the American Public Health Association (November 2009). It
      is part of his ongoing research in the social and cultural history of medicine as
      the field intersects with the history of disability, veterans, and public health,
      as well as current issues that touch all of these areas. This article introduces
      readers to perspectives on disability held by the British novelist John
      Galsworthy (1867-1933), which he developed primarily through his philanthropic
      support for and his compositions about rehabilitation programs for British and
      American soldiers disabled in the First World War (1914-1918). Readers will learn
      that Galsworthy's perspectives are as much about his identity as an individual
      with disabilities as they are about men disabled in the "war to end all wars."
      The rediscovery of Galsworthy's experiences and words more than 90 years after
      the end of World War I reveals how history is present today at the intersection
      of disability and public health. Indeed, the story of Galsworthy ultimately
      seeking to forget his own experiences during the "Great War," as well as the very
      physical and psychological disability caused by that conflict, can inspire public
      health professionals and disability rights advocates today to remember-indeed, to
      advocate for-men and women who served in battle and have returned home to realize
      renewed health and social participation despite permanent physical and
      psychological wounds. Readers will note that language used throughout this
      article to describe disability is period-specific and therefore not keeping with
      current conventions.

PMID- 21168805
TI  - A prospective study to examine the influence of secondary health conditions on
      vocational rehabilitation client employment outcomes.
AB  - BACKGROUND: Adults with disabilities experience a variety of secondary health
      conditions that have a negative association with employment. Vocational
      rehabilitation (VR) provides one possible access point for providing health
      promotion activities to help clients manage these conditions. OBJECTIVE: To build
      the case for providing health promotion services in the VR setting, this research
      assesses how secondary health conditions impact employment closures over time for
      VR clients. Specifically, we hypothesize that higher rates of secondary
      conditions will be negatively associated with employment outcomes at 18 months.
      METHODS: VR clients with physical disability (n = 162) provided longitudinal data
      at baseline and at 6, 12, and 18 months. Two binary logistic regression models
      used self-report data to predict employment outcomes. The first model used
      explanatory variables measured at baseline or prior to receiving VR services, and
      the second model measured variables after 18 months in the VR program. Both
      models included variables to control for demographic characteristics, disability
      severity, baseline employment, and receipt of social insurance payments. The
      second model also included variables to account for VR services received.
      RESULTS: Both models showed that higher reported rates of secondary conditions
      were associated with lower probabilities of employment (p = .012; p = .022). The
      expanded model also showed that receipt of counseling services through VR
      increased the probability of employment (p = .04) and that receipt of medical
      services through VR reduced the probability of employment (p = .02). CONCLUSIONS:
      VR can improve client employment outcomes through expanded counseling and
      guidance services or possibly through improved access to health promotion
      programming that helps clients manage secondary health conditions.

PMID- 21168806
TI  - Employer benefits from making workplace accommodations.
AB  - BACKGROUND: This study explored workplace disability accommodations and their
      benefits. The participants were employers and human resource professionals who
      had not used the services of the Job Accommodation Network (JAN). The companies
      included large businesses (more than 499 employees) and small businesses (fewer
      than 500 employees). OBJECTIVE/HYPOTHESIS: The intent of this investigation was
      to assess the disability accommodations and benefits for the employers. METHODS:
      The study used responses to online survey from194 employers to discuss disability
      related accommodations for an employee or potential employee. The survey included
      128 employers who reported having had a person with a disability who requested an
      accommodation. RESULTS: As reported by the employers, the most frequently
      mentioned direct benefits from implementing workplace accommodations were (a)
      retained a qualified employee, (b) increased worker productivity, and (c)
      eliminated the cost of training a new employee. The most frequently mentioned
      indirect benefits from accommodations were (a) improved interactions with
      coworkers, (b) increased overall company morale, and (c) increased overall
      company productivity. The most frequently reported types of implemented
      accommodations were buying equipment and changing work schedules. Most of the
      respondents estimated the direct benefits of having made an accommodation at more
      than $1000. CONCLUSIONS: The findings heighten awareness of benefits associated
      with making accommodations for people with disabilities in the workplace. These
      benefits signify value for business, coworkers, and individuals with disabilities
      for whom accommodations are critical for successful employment.

PMID- 21168807
TI  - Using pedometers to measure moderate-to-vigorous physical activity for youth with
      an intellectual disability.
AB  - BACKGROUND: Pedometers serve as one of the most feasible and cost-effective
      methods for frontline practitioners to measure moderate-to-vigorous physical
      activity (MVPA) of youth with an intellectual disability (YwID) but,
      historically, pedometers have been unable to measure MVPA. Technological
      advancements now allow pedometers to measure MVPA via step frequency (steps per
      minute). Translating the output of this technology into practical information
      that frontline practitioners and families can use, however, will require accurate
      step frequency guidelines. OBJECTIVE: The purpose of this study was to identify
      steps per minute thresholds corresponding to MVPA for YwID. METHODS: Thirty-eight
      children and adolescents (10 girls, 11.8 +/- 1.8 years) attending a summer camp
      for youth with an ID walked on a treadmill starting at 2.0 mph and increasing
      every 2 minutes by 0.5 mph until they reached 4.0 mph. Youth were affixed with a
      heart rate (HR) monitor. Steps were counted by trained observers using hand-tally
      counters. Data were collected during the final minute of each speed. HR at each
      speed was transformed into percentage of heart rate reserve (%HRR), using each
      participant's resting HR. Percentage of HRR corresponding to 40%HRR or higher was
      used to define MVPA. Random effects models were constructed to predict steps per
      minute from %HRR and participant characteristics. RESULTS: The results indicated
      that, on average, 122 steps.min(-1) was the minimal threshold for MVPA. Height-
      and age-specific steps.min(-1) ranged from 135 steps.min(-1) to 112 steps.min(
      1). CONCLUSIONS: These findings provide preliminary thresholds for steps per
      minute that frontline practitioners working with YwID can use to promote and
      evaluate MVPA in this population.

PMID- 21168808
TI  - Does an accelerometer accurately measure steps taken under controlled conditions
      in adults with mild multiple sclerosis?
AB  - BACKGROUND: Accurate measurement is required by researchers and clinicians who
      are interested in the physical activity behavior of individuals with multiple
      sclerosis (MS). Advances in technology have resulted in an increased number of
      motion sensors such as pedometers and accelerometers that are worn on the body
      and that measure bodily movement. Accelerometers are becoming less expensive and
      more user-friendly, but there is limited evidence regarding the accuracy of
      measurement in persons with MS. OBJECTIVE: The present study examined the
      accuracy of an ActiGraph accelerometer for measuring steps taken during
      controlled conditions in persons with MS compared with a sample of individuals
      without MS. METHODS: The participants were 24 adults with mild MS and 24 adults
      without MS who undertook three 6-minute periods of walking at 54, 80, and 107
      m.min(-1) on a motor-driven treadmill. We measured steps taken through
      observation and an ActiGraph model 7164 accelerometer worn around the waist above
      the right hip. RESULTS: The accelerometer accurately measured steps during
      moderate (80 m.min(-1)) and fast (107 m.min(-1)) walking in both persons with MS
      and control subjects. There was a small degree of underestimation of step counts
      (~4% error) for the accelerometer during slower walking (54 m.min(-1)) in both
      persons with MS and control subjects. CONCLUSIONS: Such findings support the
      accuracy of a waist worn ActiGraph accelerometer for the measurement of steps in
      persons with MS and control subjects.

PMID- 21168809
TI  - Corneal intraepithelial neoplasia: in vivo confocal microscopic study with
      histopathologic correlation.
AB  - PURPOSE: To ascertain in vivo confocal microscopic features of
      corneal/conjunctival intraepithelial neoplasia (CIN) and correlate these with
      histology of the same lesions. DESIGN: Observational case series with evaluation
      of diagnostic technology. METHODS: Four patients with unilateral CIN (3 men and 1
      woman) were examined with the Heidelberg Retina Tomograph II (HRT II) Rostock
      Cornea Module (RCM) confocal microscope before, during, and after treatment.
      Corneal epithelial samples were taken by alcohol delamination technique in 2
      patients, while impression cytology (IC) samples were obtained in the other 2
      patients. Morphometric analysis of confocal and histologic images was carried out
      and the findings correlated. Four controls (all men, 2 with limbal stem cell
      deficiency, 1 with a limbal lesion, and 1 with diffuse keratoconjunctival
      proliferation) were similarly examined. Two of these had biopsy for histologic
      examination. Main outcome measures comprised the degree of correlation between
      histology and confocal microscopic features of CIN. RESULTS: Dysplastic cellular
      changes were noticed on histopathology and correlated well with confocal
      microscopy, corresponding to the different corneal epithelial layers. Bright
      nucleoli within huge nuclei and ill-defined cell borders were a feature of the
      basal epithelium on histopathology and confocal microscopy. Subbasal corneal
      nerves were not visualized on confocal microscopy in areas affected by CIN. These
      features disappeared in response to treatment cycles as the basal epithelium
      reverted to its normal pattern, as seen by confocal microscopy. CONCLUSION:
      Confocal microscopy findings highly correlate with histologic features in CIN.
      Confocal microscopic features of CIN as defined in this study will enable a
      reliable diagnosis in a noninvasive manner. Confocal microscopy will also allow
      real-time monitoring of the condition during treatment.

PMID- 21168810
TI  - Incidence of outer foveal defect after macular hole surgery.
AB  - PURPOSE: To determine the incidence of outer foveal defects after macular hole
      surgery and to evaluate the relationship between the defect and visual outcome.
      DESIGN: Retrospective, observational case series. METHODS: A retrospective
      analysis was performed on 50 eyes from 50 patients who underwent macular hole
      surgery with a follow-up period of 12 months or more. We evaluated the presence
      of outer foveal defects using time-domain optical coherence tomography and best
      corrected visual acuity at several postoperative time points. The main outcome
      measures are the incidence of an outer foveal defect and the best-corrected
      visual acuity. RESULTS: The incidence of an outer foveal defect at 1, 3, 6, and
      12 months after surgery was 49%, 50%, 47%, and 31%, respectively. There were no
      statistical differences in the postoperative visual acuity between eyes with and
      without an outer foveal defect at each postoperative time point. CONCLUSIONS:
      Outer foveal defects after successful macular hole surgery were observed in
      approximately half of the eyes during the early postoperative period and one
      third of the eyes at 12 months postoperatively, suggesting that it takes longer
      than expected to recover the normal foveal anatomy after surgery. The presence of
      outer foveal defects did not significantly correlate with the visual outcome.

PMID- 21168811
TI  - Comparison of the correlations between optic disc rim area and retinal nerve
      fiber layer thickness in glaucoma and nonarteritic anterior ischemic optic
      neuropathy.
AB  - PURPOSE: To test whether comparison of the correlation between optic disc rim
      area and retinal nerve fiber layer thickness (rim-RNFL correlation) can
      differentiate eyes with nonarteritic anterior ischemic optic neuropathy (NAION)
      from eyes with open-angle glaucoma (OAG). DESIGN: Prospective cross-sectional
      study. METHODS: One hundred and thirteen eyes with OAG and 22 with NAION were
      included in this study. The rim-RNFL correlation in OAG eyes was analyzed in
      global and 12-clock-hour parameters using rim areas determined by Heidelberg
      retina tomography (HRT II) and RNFL thicknesses determined by optical coherence
      tomography (Cirrus OCT). The eyes with NAION were determined whether to be out of
      the 95% prediction interval (PI) for the rim-RNFL correlation of OAG in global
      and clock-hour parameters. RESULTS: A significant linear rim-RNFL correlation was
      observed in global and all clock-hour sectors, except the 3-, 4-, and 9-o'clock
      sectors, in OAG (0.045 < r(2) < 0.64, P < .05, respectively). All eyes with NAION
      were outside the 95% PI of the rim-RNFL correlation of OAG in at least 1 clock
      hour sector in terms of clock-hour parameters, as compared with 63.6% of eyes in
      terms of global parameter. All NAION eyes (n = 21) with 7- or 11-o'clock
      involvement had a rim-RNFL correlation outside the 95% PI of OAG for
      corresponding clock-hour sectors. CONCLUSIONS: By comparison of the rim-RNFL
      correlation, eyes with NAION were found to be well differentiated from OAG eyes,
      especially in clock-hour sectors. It might be an objective approach to
      discriminate NAION from OAG.

PMID- 21168812
TI  - A reappraisal of eyelid eccrine and apocrine hidrocystomas: microanatomic and
      immunohistochemical studies of 40 lesions.
AB  - PURPOSE: To establish reliable criteria for diagnosing eyelid eccrine and
      apocrine hidrocystomas. DESIGN: Retrospective clinicopathologic and
      immunohistochemical study. METHODS: Twenty-two specimens of normal portions of
      eyelids were evaluated to establish the distribution and microanatomy of eccrine
      and apocrine glands. Immunostaining for cytokeratin 7 (CK7), gross cystic disease
      fluid protein-15 (GCDFP-15), alpha-smooth muscle actin (alpha-SMA), epithelial
      membrane antigen (EMA), and carcinoembryonic antigen (CEA) was performed on these
      tissues and on 40 lesions in 33 patients diagnosed with eccrine or apocrine
      hidrocystomas by unaided light microscopy. RESULTS: Eccrine glands were not
      present in the eyelid margins, the lower half of the upper eyelid pretarsal skin,
      or the pretarsal lower eyelid skin. Apocrine glands were restricted to the eyelid
      margins and canthi where the cysts were located. GCDFP-15, CK7, and alpha-SMA
      immunoreacted with the eccrine secretory coils but not their ducts; apocrine
      gland secretory spirals also stained positively for these markers throughout
      their extended courses, but not their short terminal ducts. Positivity was found
      in 37 of 40 hidrocystomas for alpha-SMA and 19 for GCDFP-15; lesions tested for
      CK7 displayed positivity. CONCLUSIONS: Alpha-SMA-, CK7-, and/or GCDFP-15-positive
      apocrine hidrocystomas were the only type discovered in this series and arose
      from glandular secretory spirals within the marginal, perimarginal, or canthal
      skin. Three lesions did not stain for alpha-SMA, initially suggesting an absent
      myoepithelium and therefore an eccrine ductal origin; they manifested CK7
      positivity, however, another characteristic of the apocrine secretory spiral but
      not ducts. Our findings disprove the contention that eccrine predominate over
      apocrine hidrocystomas in the eyelids.

PMID- 21168813
TI  - Descemet stripping automated endothelial keratoplasty with a graft insertion
      device: surgical technique and early clinical results.
AB  - PURPOSE: To present the surgical technique and the early clinical results of the
      EndoGlide, a graft insertion device for use during Descemet stripping automated
      endothelial keratoplasty (DSAEK). DESIGN: Prospective interventional case series.
      METHODS:  PATIENTS: Graft insertion with the EndoGlide was performed in 25 eyes
      of Asian patients with endothelial dysfunction suitable for DSAEK. Demographic
      and clinical details, best-corrected visual acuity, postoperative complications,
      and endothelial cell density (ECD) loss were documented. SURGICAL TECHNIQUE: The
      prepared graft is transferred onto a preparation base and pulled into the glide
      capsule with forceps. Drawing the graft into the capsule curls it into a "double
      coil" configuration. The assembled EndoGlide is inserted into the eye, and the
      graft is pulled into the anterior chamber with forceps, where it uncoils in the
      correct orientation with minimal manipulation. RESULTS: Average age was 70 years
      (range 28-91) and the commonest diagnosis was pseudophakic bullous keratopathy
      (12 eyes). Preoperative donor ECD was 2957 +/- 242 cells/mm(2), median graft
      diameter was 8.75 mm, and all surgeries were completed successfully by 2
      surgeons. There was a short learning curve in loading of the graft into the
      EndoGlide and in uncoiling the graft in the recipient eye. No patient had graft
      dislocation or primary iatrogenic graft failure. At 6 months, the mean ECD was
      2586 +/- 338 cells/mm(2) and mean cell loss was 13.1% in 20 eyes. At 12 months,
      the mean ECD was 2575 +/- 289 cells/mm(2) and mean cell loss was 15.6% in 10
      eyes. CONCLUSIONS: Graft insertion with the EndoGlide is safe in DSAEK, with a
      short learning curve and a low endothelial cell loss at 6 and 12 months.

PMID- 21168814
TI  - Are lung disease and function related to age-related macular degeneration?
AB  - PURPOSE: To describe the relationship of lung disease and function with early age
      related macular degeneration (AMD) in a population-based study. DESIGN: A
      population-based, cross-sectional study of 12,596 middle-aged participants from
      the Atherosclerosis Risk in Communities Study. METHODS: Lung function was
      assessed by spirometry. Physician diagnosis of asthma and lung disease was
      ascertained from a standardized questionnaire. AMD signs were graded from fundus
      photographs according to the Wisconsin grading protocol. RESULTS: Among the study
      population, 587 (4.7%) had early AMD, 638 (5.1%) had asthma, and 581 (4.6%) had
      lung disease. After adjusting for age, gender, smoking, and hypertension, each 1
      L increase in predicted forced expiratory volume in 1 second (odds ratio [OR],
      1.27; 95% confidence interval [CI], 0.89 to 1.80), forced vital capacity (OR,
      1.18; 95% CI, 0.93 to 1.51), and peak expiratory flow rate (OR, 1.12; 95% CI,
      0.95 to 1.33) were not significantly associated with early AMD. Forced expiratory
      volume in 1 second-to-forced vital capacity ratio (second quartile OR, 1.61; 95%
      CI, 0.88 to 2.93, third quartile OR, 1.65; 95% CI 0.90 to 3.03; fourth quartile
      OR, 1.28; 95% CI 0.68 to 2.40) was not associated significantly with early AMD.
      Similarly, asthma (OR, 1.06; 95% CI, 0.86 to 1.27) and other lung diseases (OR,
      1.08; 95% CI, 0.90 to 1.29) were not associated with early AMD. CONCLUSIONS: Our
      data do not support a cross-sectional association between lung disease and risk
      of early AMD.

PMID- 21168816
TI  - Postoperative risk factors influencing corneal graft survival in the Singapore
      Corneal Transplant Study.
AB  - PURPOSE: To determine postoperative risk factors that influence long-term corneal
      graft survival. DESIGN: Prospective cohort study. METHODS: Nine-hundred one
      consecutive penetrating keratoplasty procedures for optical, therapeutic, or
      tectonic indications from the Singapore Corneal Transplant Study. Univariate and
      multivariate analysis was performed for postoperative risk factors; Cox
      proportional hazards regression with a time-dependent covariate was used for
      preoperative, intraoperative, donor, and postoperative risk factors in a combined
      model. RESULTS: Raised intraocular pressure (20.7%) was the most common
      complication, followed by rejection (18.2%), whereas glaucoma surgery (7.9%) and
      repeat grafting (7.3%) were the most common procedures after penetrating
      keratoplasty. The primary graft failure rate was 1.4%, and late failure was seen
      in 9.4% of eyes. In the combined regression model, rejection (hazard ratio [HR],
      3.4; P = .00), microbial keratitis (HR, 3.6; P = .00), endophthalmitis (HR, 7.7;
      P = .00), primary disease recurrence (HR, 73.9; P = .00), wound dehiscence (HR,
      2.8; P = .02), lid surgery (HR, 2.3; P = .02), glaucoma surgery (HR, 2.46; P =
      .02), and repeat grafting (HR, 3.2; P = .00) were the significant postoperative
      failure predictors; the significant preoperative and intraoperative factors
      identified were female gender, graft size of less than 7 mm and more than 9 mm,
      primary diagnosis, preoperative inflammation, and preexisting perforation.
      CONCLUSIONS: Postoperative complications and operative procedures after grafting
      have an adverse effect on graft survival.

PMID- 21168815
TI  - Cytomegalovirus retinitis and the acquired immunodeficiency syndrome--bench to
      bedside: LXVII Edward Jackson Memorial Lecture.
AB  - PURPOSE: To update information on cytomegalovirus (CMV) retinitis in patients
      with acquired immunodeficiency syndrome (AIDS) and to integrate information on
      its pathogenesis and clinical outcomes. DESIGN: Literature review. METHODS:
      Selected articles from the medical literature, particularly large epidemiologic
      studies, including the Johns Hopkins Cytomegalovirus Retinitis Cohort Study, the
      Longitudinal Study of the Ocular Complications of AIDS, and the Cytomegalovirus
      Retinitis and Viral Resistance Study, were reviewed. Clinical information is
      discussed in light of knowledge on CMV, its pathogenesis, and its interactions
      with human immunodeficiency virus (HIV). RESULTS: Cytomegalovirus uses several
      mechanisms to evade the immune system and establish latent infection in
      immunologically normal hosts. With immune deficiency, such as late-stage AIDS,
      CMV reactivates, is disseminated to the eye, and establishes a productive
      infection, resulting in retinal necrosis. HIV and CMV potentiate each other: CMV
      accelerates HIV disease, and CMV retinitis is associated with increased
      mortality. Randomized clinical trials have demonstrated the efficacy of
      treatments for CMV retinitis. Systemically administered treatment for CMV
      retinitis decreases AIDS mortality. Highly active antiretroviral therapy (HAART)
      effectively suppresses HIV replication, resulting in immune recovery, which, if
      sufficient, controls retinitis without anti-CMV therapy. Resistant CMV, detected
      in the blood, correlates with resistant virus in the eye and is associated with
      worse clinical outcomes, including mortality. Host factors, including host
      genetics and access to care, play a role in the development of CMV retinitis.
      CONCLUSIONS: Clinical outcomes of CMV retinitis in patients with AIDS are
      dependent on characteristics of the virus and host and on HIV-CMV interactions.

PMID- 21168818
TI  - Genotype/phenotype correlation in primary congenital glaucoma patients from
      different ethnic groups of the Israeli population.
AB  - PURPOSE: To investigate the roles of CYP1B1 and MYOC mutations and characterize
      the phenotype of primary congenital glaucoma in Israeli patients from 3 different
      ethnic backgrounds. DESIGN: Interventional case series. METHODS: This
      institutional study included 34 Israeli primary congenital glaucoma patients (26
      families) comprising 9 Jews (9 families), 17 non-Bedouin Muslim Arabs (10
      families), and 8 Druze (7 families). The patients and their relatives (n = 99)
      were screened for CYP1B1 and MYOC mutations. RESULTS: Mutations in the CYP1B1
      gene were detected in 12 of 26 families (46%) with primary congenital glaucoma (5
      Muslim Arab, 5 Druze, and 2 Jewish). The Jewish families had compound
      heterozygous mutations and digenic mutations (ie, an Ashkenazi family had
      mutations in the CYP1B1 gene [Arg368His, R48G, A119S, and L432V haplotypes] and
      an Ashkenazi-Sephardic family had a mutation on the CYP1B1 gene [1908delA,
      Sephardic] with a second missense mutation on the MYOC gene [R76K, Ashkenazi]).
      The Muslim Arabs and Druze tended to have a more severe phenotype than that of
      the Jews. CONCLUSION: The phenotype and spectrum of the CYP1B1 and MYOC mutation
      roles in the clinical characteristics of primary congenital glaucoma varied
      according to ethnicity. The rarity of mutations in the CYP1B1 gene among
      Ashkenazi primary congenital glaucoma patients indicates that a different locus
      may be involved in the phenotype.

PMID- 21168817
TI  - The impact of intravitreal bevacizumab therapy on choroidal melanoma.
AB  - PURPOSE: To describe the clinical course and ancillary findings of 3 patients
      with choroidal melanoma who inadvertently received multiple intravitreal
      injections of bevacizumab for a presumed diagnosis of choroidal neovascular
      membrane. DESIGN: Observational case series. METHODS: Three patients with
      choroidal melanomas who received a series of monthly intravitreal injections of
      bevacizumab for presumed choroidal neovascularization were evaluated. Clinical,
      ultrasonographic, and angiographic findings are presented. Histopathologic
      features are correlated with clinical features in 2 patients who underwent
      enucleation. RESULTS: Lack of benefit in halting tumor progression was observed
      in all 3 cases. In 2 cases treated with enucleation, there was evidence of
      bevacizumab-induced gliotic/fibrotic retinal changes. CONCLUSIONS: We present 3
      cases of choroidal melanomas that showed progression while patients received
      multiple intravitreal injections of bevacizumab. The use of the drug led to the
      formation of a gliotic/fibrotic membrane that resulted in masking of the
      underlying tumor and consequently delayed the correct diagnosis.

PMID- 21168819
TI  - Vitreous levels of angiopoietin-1 and angiopoietin-2 in eyes with retinopathy of
      prematurity.
AB  - PURPOSE: To determine the vitreous levels of angiopoietin (Ang)-1 and Ang-2 in
      eyes with retinopathy of prematurity (ROP), and to determine the correlation
      between the 2 levels. DESIGN: Retrospective case-control study. METHODS: Forty
      eight eyes with stage 4 ROP were studied. Six eyes with congenital cataract were
      used as controls. The ROP eyes were classified by the vascular activity into
      highly (n = 22), moderately (n = 15), and mildly (n = 11) vascular-active ROP.
      Eyes with highly vascular-active ROP initially received 0.5 mg of intravitreal
      bevacizumab (IVB) and underwent vitrectomy within 1 week. The others underwent
      vitrectomy without IVB. Vitreous samples were collected at the beginning of
      vitrectomy, and the vitreous levels of Angs were measured by enzyme-linked
      immunosorbent assay. RESULTS: The mean concentrations of Ang-1 and Ang-2 were
      201.9 and 7832.1 pg/mL in highly vascular-active ROP eyes, 216.1 and 7731.2 pg/mL
      in moderately vascular-active ROP eyes, 533.8 and 1685.9 pg/mL in mildly vascular
      active ROP eyes, and 0 and 41.5 pg/mL in control eyes. The vitreous Ang-1 level
      was significantly higher (P < .05) in highly, moderately, and mildly vascular
      active ROP eyes than in control eyes. The vitreous Ang-2 level was significantly
      higher (P < .05) in highly and moderately vascular-active ROP eyes than in
      control eyes. There was a significant negative correlation (r = -0.406; P = .040)
      between the Ang-1 and Ang-2 levels in moderately and mildly vascular-active ROP
      eyes. CONCLUSIONS: The balance of Ang-1 and Ang-2 in the vitreous may be
      important in the pathogenesis of ROP.

PMID- 21168820
TI  - Prognostic factors and outcomes in endogenous Klebsiella pneumoniae
      endophthalmitis.
AB  - PURPOSE: To determine risk factors for poor visual acuity outcomes in patients
      with endogenous Klebsiella pneumoniae endophthalmitis. DESIGN: Retrospective case
      control study. METHODS: We reviewed all consecutive patients diagnosed with
      endogenous Klebsiella pneumoniae endophthalmitis over 20 years. Data collected
      included patients' demographics, clinical findings, investigations, and
      therapeutic intervention. Main outcome measures were visual acuity (VA) at 3
      months postinfection and/or evisceration. Poor vision was defined as VA worse
      than 4/200. RESULTS: Seventy-one eyes of 61 patients were studied. Mean age was
      55.7 (standard deviation [SD] +/- 13.1) years. Majority were male (49/61, 80.3%),
      Chinese (51/61, 83.6%), and had hepatobiliary sepsis (47/61, 77.5%). Mean time to
      ocular symptoms was 4.4 (+/- 3.0) days. Fifty-four of 71 eyes (80.2%) had poor
      vision and 19/71 eyes (26.8%) required evisceration. The most significant risk
      factor was hypopyon (41/71 eyes, 57.7%) on multivariate analysis (odds ratio
      [OR], 52.6; 95% confidence interval [CI], 1.7-1000; P = .01). Unilateral
      involvement (OR, 10.4; 95% CI, 1.2-90.2; P = .01) and patients that were managed
      before year 2000 (before routine screening was implemented) (OR, 5.2; 95% CI, 1.5
      17.9; P = .037) were significant risk factors for evisceration on multivariate
      analysis. CONCLUSION: Patients presenting with hypopyon and unilateral
      involvement have a poorer prognosis.

PMID- 21168821
TI  - Survey of intravitreal injection techniques among retinal specialists in the
      United States.
AB  - PURPOSE: To describe the intravitreal injection technique practice patterns of
      retinal specialists in the United States from April 8, 2010 to April 21, 2010.
      DESIGN: Questionnaire survey. METHODS: All members of the American Academy of
      Ophthalmology who self-categorized as "Retinal/Vitreous Surgery" were contacted
      by e-mail to complete an anonymous, 20-question, internet-based survey. RESULTS:
      A total of 765 retinal specialists (44%) responded to the survey. Most
      respondents wear gloves (58%) and use an eyelid speculum (92%) when performing an
      intravitreal injection. More than 99% use povidone-iodine preinjection. The
      majority measure the injection site from the limbus (56%) and inject straight
      into the vitreous cavity (96%). Most do not displace the conjunctiva (83%).
      Seventy-two percent routinely assess postinjection optic nerve perfusion,
      primarily by gross visual acuity measurement (32%). While nearly one third of
      participants use prophylactic topical antibiotics preinjection, more than two
      thirds use topical antibiotics postinjection. Forty-six percent perform bilateral
      simultaneous intravitreal injections. The majority of respondents use a 30-gauge
      needle for the injection of ranibizumab (78%) and bevacizumab (60%). However,
      respondents use both a 27- and 30-gauge needle for the injection of triamcinolone
      acetonide. CONCLUSIONS: Retinal specialists in the United States participate in a
      range of techniques for the care before, during, and after intravitreal
      injections. Further study is needed to elucidate best practice patterns.

PMID- 21168822
TI  - Intravitreal injection anesthesia--comparison of different topical agents: a
      prospective randomized controlled trial.
AB  - PURPOSE: To compare the anesthetic effectiveness of 3 topical agents used for
      intravitreal injections. DESIGN: Randomized, triple-armed, double-blinded,
      prospective, single-centered trial in patients receiving intravitreal ranibizumab
      for neovascular age-related macular degeneration. METHODS: Patients were
      randomized 1:1:1 to receive 0.5% tetracaine hydrochloride drops and a 4%
      lidocaine pledget (n = 31), 0.5% tetracaine hydrochloride drops alone (n = 31),
      or 4% cocaine (+ epinephrine 1/100,000) drops alone (n = 31). Patients were asked
      to score their pain experience using a visual analogue scale (VAS) immediately
      following and 15 minutes after their injection. The average of these scores was
      used as the primary outcome. The physician performing the procedure separately
      scored his perception of the patients' pain using the Wong-Baker FACES scale.
      RESULTS: Means of the averaged VAS pain score for Groups 1, 2, and 3 were: 19
      (95% confidence interval [CI] 12-26), 21 (95% CI 13-29), and 21 (95% CI 16-27)
      respectively. Mean Wong-Baker pain scores for Groups 1, 2, and 3 were 1.9 (95% CI
      1.3-2.6), 2.1 (95% CI 1.4-2.7), and 2.3 (95% CI 1.6-3.1) respectively. There was
      no significant difference (P = .549) between groups for average VAS pain score.
      Similarly, there was no significant difference (P = .790) for the physician
      perceived pain score between groups. CONCLUSIONS: There was no clinical
      difference in patient pain experience between the 3 anesthetic options tested.
      The addition of a 4% lidocaine pledget offered no clinical advantage in pain
      relief compared to 0.5% tetracaine or 4% cocaine (+ epinephrine 1/100,000) drops
      alone.

PMID- 21168823
TI  - Pars plana vitrectomy with endoscope-guided sutured posterior chamber intraocular
      lens implantation in children and adults.
AB  - PURPOSE: To describe a novel method for placement of a sulcus-fixated, sutured
      posterior chamber intraocular lens (sf-SPC-IOL) using endoscopic guidance during
      pars plana vitrectomy surgery. DESIGN: A retrospective case-series by a single
      surgeon in both pediatric and adult patients undergoing sf-SPC-IOL in the setting
      of posterior segment surgery. METHODS: Seventy-four eyes of 71 patients had pars
      plana vitrectomy and placement of an sf-SPC-IOL in an academic, outpatient
      setting. Preoperative diagnosis included trauma (42%), subluxated lenses with no
      capsular support (24%), uveitis (15%), congenital cataract (11%), Marfan syndrome
      or ectopia lentis (6%), and other (2%). Fifty-one adults and 20 children (<18
      years of age) were reviewed from cases performed from 1999 through 2007. The sf
      SPC-IOL sutures were placed using endoscopic visualization of ab interno scleral
      fixation. RESULTS: The mean follow-up time was nearly 3 years (3 months to 9
      years) and most patients experienced an improvement in visual function. Many eyes
      had advanced posterior segment disorders. Only 2 broken sutures occurred, both
      attributable to repeat trauma. Advantages of this technique include: excellent
      visualization and haptic localization, optimal lens centration, buried knots,
      broad scleral imbrication, and minimal vitreous- and hemorrhage-related
      complications. Disadvantages include the learning curve, increased operative
      time, long-term suture stability issues, and limited availability of intraocular
      endoscopes. CONCLUSIONS: Endoscopic-guided sf-SPC-IOL using this approach, in the
      setting of posterior segment disease, is a reasonable option for visual
      rehabilitation in both pediatric and adult patients.

PMID- 21168824
TI  - Microperimetric changes after photodynamic therapy for central serous
      chorioretinopathy.
AB  - PURPOSE: To evaluate the effect of half-dose verteporfin photodynamic therapy
      (PDT) on macular function in cases of central serous chorioretinopathy (CSC).
      DESIGN: Interventional case series. METHODS: A total of 24 eyes from 24 cases of
      CSC were included in this study. In each eye, at baseline and 1, 3, and 6 months
      after half-dose PDT, logMAR best-corrected visual acuity (BCVA); central 10
      degree, 20-degree, and paracentral 10-degree to 20-degree retinal sensitivity;
      and also mean retinal sensitivity results for each case over the area that was
      treated with half-dose PDT (PDT spot area) by MP-1 microperimetry and optical
      coherence tomography (OCT) foveal morphologic changes were assessed. The MP-1
      microperimetry sensitivity map was overlaid onto an indocyanine green angiography
      image recorded on a Heidelberg scanning laser ophthalmoscope using dedicated MP-1
      software to evaluate the PDT laser spot area. RESULTS: After treatment, BCVA and
      central 10-degree, 20-degree, paracentral 10-degree to 20-degree, and PDT laser
      spot area retinal sensitivity were improved significantly. In OCT in 20 of 24
      eyes (83%), subretinal fluid (SRF) was resolved 1 month after half-dose PDT. At 3
      and 6 months after treatment, SRF was resolved at all eyes. None of the patients
      in this study developed any systemic or ocular adverse events associated with
      verteporfin treatment. CONCLUSION: Half-dose verteporfin PDT induced a
      significant increase in central 10-degree, 20-degree, paracentral 10-degree to 20
      degree, and also PDT laser spot area retinal sensitivity over 6 months in cases
      of CSC.

PMID- 21168825
TI  - Selenium and pseudoexfoliation syndrome.
AB  - PURPOSE: To investigate the levels of selenium (Se), an essential trace element,
      in aqueous humor, conjunctival specimens, and serum of patients with
      pseudoexfoliation (PEX) syndrome and control subjects; and to determine the role
      of Se in the development and pathogenesis of PEX syndrome. DESIGN: A prospective
      case-control study. METHODS: Twenty-seven cataract patients with PEX syndrome and
      20 age-matched cataract patients without PEX syndrome were enrolled in this
      institutional study. Patients with ophthalmic conditions other than PEX and
      conditions that may influence Se levels were excluded. During cataract surgeries,
      aqueous humor, conjunctival specimens, and serum were collected in both groups.
      Selenium levels of all samples were measured by using atomic absorption
      spectrophotometer. RESULTS: The mean Se levels in aqueous humor of patients with
      PEX syndrome (50.96 +/- 23.79 MUg/L) were significantly lower than the control
      group (77.85 +/- 19.21 MUg/L) (P < .001). The mean Se levels in conjunctival
      specimens of patients with PEX syndrome (4.04 +/- 1.44 MUg/mg) were significantly
      lower than the control group (7.19 +/- 2.00 MUg/mg) (P < .001), as well. The mean
      Se levels in serum of patients with PEX syndrome (115.25 +/- 25.20 MUg/L) were
      lower than the control group (124.25 +/- 14.40 MUg/L), but this was not
      statistically significant (P = .325). CONCLUSION: Reduced levels of Se in aqueous
      humor, conjunctival specimens, and serum of patients with PEX may support the
      role of impairment in antioxidant defense system in the pathogenesis of PEX
      syndrome.

PMID- 21168826
TI  - The outcome of early surgical repair with vitrectomy and silicone oil in open
      globe injuries with retinal detachment.
AB  - PURPOSE: To determine the functional and anatomic outcome of early surgical
      repair with vitrectomy and silicone oil in open-globe injuries with retinal
      detachment (RD). DESIGN: Retrospective consecutive interventional case series.
      METHODS: All patients with open-globe injuries with RD treated between 1997 and
      2007 underwent primary repair including vitrectomy with silicone oil within 8
      hours after presentation. For data analysis, patients were divided into 3 groups
      according to the BETT classification: Group 1, intraocular foreign body; Group 2,
      penetrating injury; Group 3, globe rupture. Outcome measures were final reading
      visual acuity (0.4 logMAR or better), final ambulatory visual acuity (1.6 logMAR
      or better), endophthalmitis, and postoperative proliferative vitreoretinopathy
      (PVR). RESULTS: Eighty-eight patients were included (Group 1, n = 13; Group 2, n
      = 36; Group 3, n = 39). Mean follow-up was 22 months (standard deviation [SD] =
      23, range 6-107 months). Eight percent of patients retained reading vision
      without significant difference between the 3 groups. Fewer patients in Group 3
      than in Group 1 or 2 retained ambulatory visual acuity (Group 1, 62%; Group 2,
      64%; Group 3, 33%, P = .024). Endophthalmitis occurred in 3.4% of eyes (1 eye in
      each group). PVR grade B-C, type 1-3 developed in 44% of patients without
      significant difference between the 3 groups. Re-RD occurred in 38% of eyes.
      CONCLUSIONS: Few patients achieved reading vision while 50% of patients retained
      ambulatory visual acuity. Final visual outcome is related to the severity of the
      injury. The frequency of postoperative endophthalmitis is low. Postoperative
      development of advanced PVR is avoided in most patients.

PMID- 21168827
TI  - Extending hierarchical task analysis to identify cognitive demands and
      information design requirements.
AB  - While hierarchical task analysis (HTA) is well established as a general task
      analysis method, there appears a need to make more explicit both the cognitive
      elements of a task and design requirements that arise from an analysis. One way
      of achieving this is to make use of extensions to the standard HTA. The aim of
      the current study is to evaluate the use of two such extensions--the sub-goal
      template (SGT) and the skills-rules-knowledge (SRK) framework--to analyse the
      cognitive activity that takes place during the planning and delivery of
      anaesthesia. In quantitative terms, the two methods were found to have relatively
      poor inter-rater reliability; however, qualitative evidence suggests that the two
      methods were nevertheless of value in generating insights about anaesthetists'
      information handling and cognitive performance. Implications for the use of an
      extended HTA to analyse work systems are discussed.

PMID- 21168828
TI  - Epithelial-stromal interactions in salivary glands of rats exposed to chronic
      passive smoking.
AB  - OBJECTIVES: Cigarette smoke leads to precancerous and cancerous lesions in the
      mouth even when the exposure is passive. The salivary glands are amongst the
      tissues exposed to the smoke but it is unclear whether or not passive cigarette
      exposure is related to detectable changes in these tissues. The objective of this
      study was to observe the tissue architecture of the parotid and submandibular
      glands in rats after passive cigarette exposure and to measure any changes that
      occurred. DESIGN: Twenty Wistar rats were divided into 10 non-smoking animals and
      10 animals exposed to cigarette smoke. After 6 months of smoke exposure samples
      were collected from both exposed and unexposed salivary glands for histological
      examination under both transmitted and polarized light microscopy. RESULTS:
      Changes in the glands of exposed animals included involution of the cytoplasm and
      nucleus of the acinar cells and the presence of an inflammatory infiltrate. There
      was an abnormal accumulation of type I collagen in the stroma and an enlarged
      interacinar space filled with extracellular matrix. CONCLUSION: Passive smoking
      led to substantial structural changes in the salivary glands which could
      significantly affect function.

PMID- 21168829
TI  - Structure of the O-polysaccharide and characterization of the O-antigen gene
      cluster of Salmonella enterica O53.
AB  - The O-polysaccharide (O-antigen) of Salmonella enterica O53 was isolated by mild
      acid degradation of the lipopolysaccharide and studied by sugar analysis and (1)H
      and (13)C NMR spectroscopy before and after O-deacetylation. The following
      structure of the tetrasaccharide O-unit was established: Sequencing of the O
      antigen gene cluster of S. enterica O53 revealed 11 open reading frames having
      the same transcriptional direction. The functions were tentatively assigned to
      the genes based on their similarity to related genes from the available databases
      and taking into account the S. enterica O53-polysaccharide structure.

PMID- 21168830
TI  - [Transanal resection using a single port trocar: a new approach to NOTES].
AB  - INTRODUCTION: The morbidity and mortality, along with the functional changes that
      arise from radical surgery of rectal cancer, has led to an increasing interest in
      local treatment in the early stages of cancer of the rectum. Conventional
      transanal surgery has a high recurrence rate, for this reason transanal
      endoscopic microsurgery (TEM) is considered the treatment of choice in the last
      few years in large rectal adenomas and in early rectal cancer (low risk T1).
      PATIENTS AND METHOD: We have intervened five patients, four with a diagnosis of
      villous adenoma of the rectum, and one in situ rectal carcinoma, using this new
      transanal approach, with a single port device. RESULTS: The locations of the
      lesions were in the mid-rectum, at a mean distance of 9 cm (range 6-10) from the
      anal margin. All of them were situated in the posterior side. The resection
      margins were negative in all cases. The mean size of the adenomas was 4 cm, three
      being sessile shaped, and one with a short, thick pedicle (>1cm); the size of the
      carcinoma was 3 cm. The mean surgical time was 55 minutes. All the patients were
      discharged 48 hours after the surgical procedure. CONCLUSION: We believe that the
      transanal endoscopic approach with a single port device is a simple, easily
      reproducible and cost-effective procedure when compared to TEM.

PMID- 21168831
TI  - [Study of accessibility costs and satisfaction comparing a MAS unit incorporated
      in a Hospital versus a theoretical model in a peripheral centre].
AB  - INTRODUCTION: Geographical barriers are a determining factor in the accessibility
      of Hospital health care, and structural changes to improve geographic
      accessibility must be introduced. The purpose of this study is to compare
      accessibility costs and the level of satisfaction obtained in an adapted
      Specialist Centre with a peripheral MAS (Major Ambulatory Surgery) Unit, with an
      already existing one incorporated into the Virgen de la Luz Hospital (Cuenca,
      Spain) to obtain quality health care in the sub-population nearest the peripheral
      Centre. MATERIAL AND METHODS: A study was made on a comparison of the costs
      attributable to accessibility of 133 patients operated on due to hernia disorders
      in 2008 in the Cuenca Hospital of Castille-La Mancha Health Service (SESCAM), and
      who lived in its health area. These were compared using a simulation study for an
      ambulatory surgical Centre, functionally operational, but with no Major
      Ambulatory Surgery activity nearest to this patient population. The opinions of
      the patients and the increased cost-effectiveness for each alternative proposal
      were studied. RESULTS: The accessibility cost, taking into account the
      theoretical use of the Ambulatory Centre would be 208,028.09 ? and the real costs
      of the Hospital were 209,088.94 ?, with a minimum difference between the two of
      1,060.85 ?, assuming similar clinical results. CONCLUSIONS: Although there are no
      significant differences in accessibility costs by using an ambulatory surgery
      Centre compared to the Hospital, a special assessment of the use of the former is
      important, expressed in the satisfaction of the patients.

PMID- 21168832
TI  - Developmental changes in infants' visual short-term memory for location.
AB  - To examine the development of visual short-term memory (VSTM) for location, we
      presented 6- to 12-month-old infants (N=199) with two side-by-side stimulus
      streams. In each stream, arrays of colored circles continually appeared,
      disappeared, and reappeared. In the changing stream, the location of one or more
      items changed in each cycle; in the non-changing streams the locations did not
      change. Eight- and 12.5-month-old infants showed evidence of memory for multiple
      locations, whereas 6.5-month-old infants showed evidence of memory only for a
      single location, and only when that location was easily identified by salient
      landmarks. In the absence of such landmarks, 6.5-month-old infants showed
      evidence of memory for the overall configuration or shape. This developmental
      trajectory for spatial VSTM is similar to that previously observed for color
      VSTM. These results additionally show that infants' ability to detect changes in
      location is dependent on their developing sensitivity to spatial reference
      frames.

PMID- 21168833
TI  - Prevalence of nickel sensitization and urinary nickel content of children are
      increased by nickel in ambient air.
AB  - In a cross-sectional study performed in 2000, an unexpected positive association
      between nickel (Ni) in ambient air, urinary Ni content and the prevalence of Ni
      sensitization in a subgroup of 6-yr-old children living near a steel mill was
      observed. Between 2005 and 2006, in a different and larger study population, we
      examined if Ni from ambient air or urinary Ni concentration was related to Ni
      sensitization in children living next to Ni-emitting steel mills. We studied 749
      school beginners living in four Ni-polluted industrial areas of North Rhine
      Westphalia, Germany. We assessed Ni in ambient air, Ni in urine from children and
      mothers, and Ni in tap water, conducted patch tests in children (including the
      NiSO(4)-dilution test) and collected questionnaire data. Statistics were done by
      linear and logistic regression analyses, adjusted for covariates. At increased Ni
      concentration in ambient air (unit of increase: 10 ng/m(3)), urinary Ni
      concentrations rose in both mothers (9.1%; 95% CI: 6.8-11.4%) and children (2.4%;
      95% CI: 0.4-4.4%). The prevalence of Ni sensitization in children was associated
      with increased Ni from ambient air (unit of increase: 18 ng/m(3); odds ratio
      1.28; 95% CI: 1.25-1.32) and urinary Ni concentration (unit of increase: 7.1
      MUg/L; odds ratio 2.4; 95% CI: 1.20-4.48). Ni in ambient air of areas with Ni
      emitting factories contributes to internal Ni exposure in residents via
      inhalation and, furthermore, is a risk factor for the development of Ni
      sensitization in children.

PMID- 21168834
TI  - PEG rescue with gastropexy after early tube withdrawal: an application of natural
      orifice transluminal endoscopic surgery (with video).

PMID- 21168836
TI  - Pneumopericardium after panendoscopy.

PMID- 21168835
TI  - Endoscopic trimodal imaging versus standard video endoscopy for detection of
      early Barrett's neoplasia: a multicenter, randomized, crossover study in general
      practice.
AB  - BACKGROUND: Endoscopic trimodal imaging (ETMI) may improve detection of early
      neoplasia in Barrett's esophagus (BE). Studies with ETMI so far have been
      performed in tertiary referral settings only. OBJECTIVE: To compare ETMI with
      standard video endoscopy (SVE) for the detection of neoplasia in BE patients with
      an intermediate-risk profile. DESIGN: Multicenter, randomized, crossover study.
      SETTING: Community practice. PATIENTS AND METHODS: BE patients with confirmed low
      grade intraepithelial neoplasia (LGIN) underwent both ETMI and SVE in random
      order (interval 6-16 weeks). During ETMI, BE was inspected with high-resolution
      endoscopy followed by autofluorescence imaging (AFI). All visible lesions were
      then inspected with narrow-band imaging. During ETMI and SVE, visible lesions
      were sampled followed by 4-quadrant random biopsies every 2 cm. MAIN OUTCOME
      MEASUREMENTS: Overall histological yield of ETMI and SVE and targeted
      histological yield of ETMI and SVE. RESULTS: A total of 99 patients (79 men, 63+/
      10 years) underwent both procedures. ETMI had a significantly higher targeted
      histological yield because of additional detection of 22 lesions with LGIN/high
      grade intraepithelial neoplasia (HGIN)/carcinoma (Ca) by AFI. There was no
      significant difference in the overall histological yield (targeted+random)
      between ETMI and SVE. HGIN/Ca was diagnosed only by random biopsies in 6 of 24
      patients and 7 of 24 patients, with ETMI and SVE, respectively. LIMITATIONS:
      Inspection, with high-resolution endoscopy and AFI, was performed sequentially.
      CONCLUSION: ETMI performed in a community-based setting did not improve the
      overall detection of dysplasia compared with SVE. The diagnosis of dysplasia is
      still being made in a significant number of patients by random biopsies. Patients
      with a confirmed diagnosis of LGIN have a significant risk of HGIN/Ca. ( CLINICAL
      TRIAL REGISTRATION NUMBER: ISRCTN91816824; NTR867.).

PMID- 21168837
TI  - A case of EUS-guided FNA-related pancreatic cancer metastasis to the stomach.

PMID- 21168839
TI  - Endoscopic radiofrequency ablation of cholangiocarcinoma: new palliative
      treatment modality (with videos).

PMID- 21168838
TI  - Balanced propofol sedation for therapeutic GI endoscopic procedures: a
      prospective, randomized study.
AB  - BACKGROUND: There are few controlled studies on balanced propofol sedation (BPS)
      for therapeutic endoscopy. OBJECTIVE: To compare the safety and efficacy of BPS
      (propofol in combination with midazolam and meperidine) with conventional
      sedation (midazolam and meperidine) in patients undergoing therapeutic endoscopic
      procedures. DESIGN: Prospective, randomized, single-blinded study. SETTING:
      Tertiary-care referral center. PATIENTS: This study involved 222 consecutive
      patients undergoing therapeutic EGD or ERCP from July 2009 to March 2010.
      INTERVENTION: Conventional sedation or BPS by trained registered nurses under
      endoscopist supervision. MAIN OUTCOME MEASUREMENTS: Rates of sedation-related
      cardiopulmonary complications and interruption of the procedures, procedure
      related times, and assessments of health care providers (endoscopists and
      sedation nurses) and patients. RESULTS: There were no significant differences
      between the BPS and conventional groups in the rates of cardiopulmonary
      complications (8.8% [9/102] vs 5.8% [6/104], respectively) and transient
      interruption of procedures (2.9% [3/102] vs 0% [0/104], respectively). No patient
      required assisted ventilation or premature termination of a procedure. BPS
      provided significantly higher health care provider satisfaction (mean+/-SD 10-cm
      visual analog scale [VAS] score) compared with conventional sedation
      (endoscopists: 7.57+/-2.61 vs 6.55+/-2.99, respectively; P=.011; sedation nurses:
      7.86+/-2.31 vs 6.67+/-2.90, respectively; P=.001). Patient cooperation was
      significantly better in the BPS group (VAS; endoscopists: 7.24+/-2.97 vs 6.27+/
      3.09, P=.024; sedation nurses: 7.75+/-2.30 vs 6.54+/-2.99, P=.001). LIMITATIONS:
      Single-center and single-blinded study. CONCLUSION: Compared with conventional
      sedation, BPS provides higher health care provider satisfaction, better patient
      cooperation, and similar adverse event profiles in patients undergoing
      therapeutic endoscopic procedures.

PMID- 21168840
TI  - An endoscopist-blinded, randomized, controlled trial of a simple visual aid to
      improve bowel preparation for screening colonoscopy.
AB  - BACKGROUND: The effect of patient education on bowel preparation for colonoscopy
      has not been well studied. An improvement in patient understanding of the
      rationale for bowel preparation before colonoscopy might enhance adherence to the
      prescribed bowel regimen and improve bowel preparation quality. OBJECTIVE: To
      measure the effect of a simple educational intervention on the quality of bowel
      preparation during colonoscopy. DESIGN: Prospective, single-center, endoscopist
      blinded, randomized, controlled trial. SETTING: Tertiary-care center. PATIENTS:
      This study involved outpatients directly referred for screening colonoscopy.
      INTERVENTION: Inclusion of a visual aid depicting both clean and dirty colons in
      addition to standard written colonoscopy instructions. MAIN OUTCOME MEASUREMENTS:
      The primary outcome was the quality of the bowel preparation according to the
      Boston Bowel Preparation Scale (BBPS). Secondary outcomes included the need for
      repeat colonoscopy because of inadequate bowel preparation, insertion and
      withdrawal time, polyps detected, and patient tolerance of bowel preparation and
      colonoscopy. RESULTS: We analyzed 492 patients given a visual aid and 477
      controls. The percentage of colonoscopies with a BBPS score>=5 was similar in
      both groups (91% visual aid vs 89% control, P=.43). The odds ratio for having a
      BBPS>=5 in the visual aid group was 1.24 (95% CI, 0.83-1.87) compared with
      controls. Other secondary outcomes were similar between groups. LIMITATIONS:
      Single-center study. CONCLUSION: A simple card with photographs and text
      explaining the rationale for bowel preparation did not change the quality of
      bowel preparation in patients directly referred for screening colonoscopy. Future
      educational studies may need to include more interactive or intensive methods. (
      CLINICAL TRIAL REGISTRATION NUMBER: NCT00643682.).

PMID- 21168841
TI  - Computer-assisted personalized sedation for upper endoscopy and colonoscopy: a
      comparative, multicenter randomized study.
AB  - BACKGROUND: The SEDASYS System is an investigational computer-assisted
      personalized sedation system integrating propofol delivery with patient
      monitoring to enable endoscopist/nurse teams to safely administer propofol.
      OBJECTIVE: To compare the safety and effectiveness of the SEDASYS System to the
      current standard of care for sedation during routine endoscopic procedures.
      DESIGN: Nonblinded multicenter randomized comparative study. SETTING: Four
      ambulatory surgery centers, 3 endoscopy centers, and 1 academic center in the
      United States. PATIENTS: One thousand American Society of Anesthesiologists
      physical status class I to III adults undergoing routine colonoscopy or EGD.
      INTERVENTIONS: Sedation with the SEDASYS System (SED) and sedation with each
      site's current standard of care (CSC; benzodiazepine/opioid combination). MAIN
      OUTCOME MEASUREMENTS: Area under the curve of oxygen desaturation was the primary
      endpoint. Secondary endpoints included patient satisfaction, clinician
      satisfaction, level of sedation, and patient recovery time. RESULTS: Four hundred
      ninety-six patients were randomized to SED and 504 to CSC. Area under the curve
      of oxygen desaturation was significantly lower for SED (23.6 s.%) than for CSC
      (88.0 s.%; P = .028). Patients were predominately minimally to moderately sedated
      in both groups. SED patients were significantly more satisfied than CSC patients
      (P = .007). Clinician satisfaction was greater with SED than with CSC (P < .001).
      SED patients recovered faster than CSC patients (P < .001). The incidence of
      adverse events was 5.8% in the SED group and 8.7% in the CSC group. LIMITATIONS:
      Nonblinded. CONCLUSIONS: The SEDASYS System could provide endoscopist/nurse teams
      a safe and effective on-label means to administer propofol to effect minimal to
      moderate sedation during routine colonoscopy and EGD.

PMID- 21168842
TI  - Endoscopic visible light spectroscopy: a new, minimally invasive technique to
      diagnose chronic GI ischemia.
AB  - BACKGROUND: The diagnosis of chronic GI ischemia (CGI) remains a clinical
      challenge. Currently, there is no single simple test with high sensitivity
      available. Visible light spectroscopy (VLS) is a new technique that noninvasively
      measures mucosal oxygen saturation during endoscopy. OBJECTIVE: To determine the
      diagnostic accuracy of VLS for the detection of ischemia in a large cohort of
      patients. DESIGN: Prospective study, with adherence to the Standards for
      Reporting of Diagnostic Accuracy. SETTING: Tertiary referral center. PATIENTS:
      Consecutive patients referred for evaluation of possible CGI. INTERVENTIONS:
      Patients underwent VLS along with the standard workup consisting of evaluation of
      symptoms, GI tonometry, and abdominal CT or magnetic resonance angiography. MAIN
      OUTCOME MEASUREMENTS: VLS measurements and the diagnosis of CGI as established
      with the standard workup. RESULTS: In 16 months, 121 patients were included: 80
      in a training data set and 41 patients in a validation data set. CGI was
      diagnosed in 89 patients (74%). VLS cutoff values were determined based on the
      diagnosis of CGI and applied in the validation data set, and the results were
      compared with the criterion standard, resulting in a sensitivity and specificity
      of VLS of 90% and 60%, respectively. Repeated VLS measurements showed improvement
      in 80% of CGI patients after successful treatment. LIMITATIONS: Single-center
      study; only 43% of patients had repeated VLS measurements after treatment.
      CONCLUSIONS: VLS during upper endoscopy is a promising easy-to-perform and
      minimally invasive technique to detect mucosal hypoxemia in patients clinically
      suspected of having CGI, showing excellent correlation with the established
      ischemia workup.

PMID- 21168843
TI  - Metric dimensions of the proximal phalanges of the human hand and their
      relationship to side, position, and asymmetry.
AB  - The anatomy of the proximal phalanges of the human hand has been widely
      described. Nevertheless, when consulting osteology and anatomy publications, the
      general opinion of researchers is that siding and allocating the proximal
      phalanges with regard to finger position is difficult, if not impossible. We
      provide morphological criteria for determining the side of the proximal phalanges
      and a metric means of allocating a phalanx to a specific finger. This paper also
      quantifies the absolute and directional asymmetry found in phalanges within this
      sample. The sample studied consists of three groups, one modern and two
      archaeological. To investigate these, three measurements were taken-maximum
      length, maximum width at the base and maximum width at the head. It was found
      that phalanges could be assigned correctly to the side and finger of origin in
      100% of the cases when the five phalanges of a given hand were present, and that
      this result dropped to 92% when allocating isolated phalanges. The means of the
      measurements taken were larger in the modern group and a constant relationship
      between the greater basal width of the second and the fourth proximal phalanges
      was found.

PMID- 21168844
TI  - Long-term use of oral nicorandil stabilizes coronary plaque in patients with
      stable angina pectoris.
AB  - OBJECTIVE: The Impact of Nicorandil in Angina (IONA) trial demonstrated that the
      use of nicorandil, an anti-anginal drug, reduced future cardiovascular events in
      patients with stable angina. We hypothesized that nicorandil has beneficial
      effects on coronary arterial plaque characteristics and atherosclerogenesis.
      METHODS AND RESULTS: Preintervention intravascular ultrasound-virtual histology
      was performed prospectively in 65 consecutive patients with stable angina
      pectoris. There were no differences in coronary risk factors between the
      nicorandil (n = 16) and non-nicorandil (n = 49) groups. However, the nicorandil
      group demonstrated a larger %fibrous tissue (68 +/- 10 vs. 62 +/- 11%, P = 0.049)
      and a smaller %necrotic core tissue (11 +/- 7 vs. 16 +/- 10%, P = 0.049) compared
      with the non-nicorandil group. Multiple regression analysis showed that %necrotic
      core tissue (P = 0.045) was negatively and %fibrous tissue (P = 0.026) was
      positively associated with the use of nicorandil independent of statin use. We
      also analyzed the effect of nicorandil on atherosclerotic lesion formation in a
      mouse model of atherosclerosis. Lipid profiles were unaffected, but the area of
      atherosclerotic lesion and plaque necrosis were significantly reduced following 8
      week nicorandil treatment in ApoE-deficient mice fed an atherogenic diet.
      Nicorandil significantly reduced the expression levels of endoplasmic reticulum
      stress markers, C/EBP homologous protein (CHOP) and glucose regulated protein/BiP
      (GRP78) in atherosclerotic lesions. Nicorandil significantly attenuated
      tunicamycin-induced CHOP upregulation in cultured THP-1 macrophages. CONCLUSIONS:
      Nicorandil exerts its anti-atherogenic effect by mechanisms different from those
      of statins. Long-term nicorandil treatment is a potentially suitable second-line
      prevention therapy for patients with coronary artery disease.

PMID- 21168845
TI  - Modeling costal cartilage using local material properties with consideration for
      gross heterogeneities.
AB  - Contemporary computer models of the thorax designed to predict injury in
      automobile collisions model the costal cartilage as a homogeneous material using
      properties derived from local material characterization tests. No studies have
      validated the accuracy of these models in predicting the structural mechanics of
      costal cartilage. Two heterogeneities - the perichondrium and calcified regions -
      may affect the behavior of costal cartilage in a manner not accounted for by
      current models. This study sought to investigate the predictive ability of
      subject-specific models of whole costal cartilage segments, with the calcified
      regions modeled distinctly and with the perichondrium removed (from the physical
      specimens as well as from the simulations). Finite element models were developed
      in the case of five cadaveric costal cartilage segments. The properties of the
      cartilage were derived from indentation testing of each specimen, where the
      characteristic average instantaneous elastic moduli ranged from 8.7 to 12.6 MPa.
      Matched simulations and experiments were then performed, subjecting each specimen
      to cantilever-like loading with a dynamic posterior displacement of the sternal
      boundary (all other boundary degrees-of-freedom fixed). The models predicted the
      resulting peak anterior-posterior forces generated on the costal boundary with a
      minimum error of 1% and a maximum error of 36%. These results provide support to
      the previous implicit assumption that insight can be gained into the structural
      behavior of costal cartilage by observing the local material properties (when
      calcified regions are included and the perichondrium is removed). Future work
      includes the addition of the perichondrium, so as to model the whole costal
      cartilage composite structure.

PMID- 21168846
TI  - A validated model for the simulation of protein purification through affinity
      membrane chromatography.
AB  - A mathematical model is proposed for the description of protein purification
      through membrane affinity chromatography. The model describes all the three
      stages of the chromatographic cycle and takes into account convection, axial
      dispersion and binding reaction kinetics in the porous membrane matrix, while
      boundary layer mass transfer resistance is shown to be negligible. All the model
      parameters have a precise physical meaning which enables their evaluation through
      separate experimental measurements, independent of the chromatographic cycle.
      Model testing and validation has been performed with experimental chromatographic
      cycles carried out with pure IgG solutions as well as with complex mixtures
      containing IgG(1), using new affinity membranes. The comparison between model
      calculations and experimental data showed good agreement for all stages of the
      affinity cycle. In particular, for loading and washing steps binding kinetics was
      found so fast that adsorption equilibrium was sufficient to describe the observed
      behavior; as a result, the model simulations are entirely predictive for the
      adsorption and washing phases. On the contrary, in the elution step the reaction
      rate is comparable to that of the other simultaneous transport phenomena. The
      model is able to predict the performance of chromatographic purification of IgG
      from complex mixtures simply on the basis of the parameter values obtained from
      pure IgG solutions.

PMID- 21168847
TI  - Application of a modified linear solvation energy relationship (LSER) model to
      retention on a butylimidazolium-based column for high performance liquid
      chromatography.
AB  - Previously, a new HPLC stationary phase based on n-butylimidazolium bromide was
      investigated using a linear solvation energy relationship (LSER) to
      systematically evaluate the intermolecular interactions between 32 test solutes
      and the stationary phase. The results and further comparisons with conventional
      reversed phase systems revealed that retention properties are similar to phenyl
      phases in both methanol/water and acetonitrile/water mixtures. In this work, the
      LSER model is extended by including the degree of ionization molecular
      descriptor, D, which takes into account the pK(a) of ionizable analytes and the
      pH of the mobile phase. The D molecular descriptor has been further divided into
      D(+) and D(-) components that separately account for the ionization of basic and
      acidic solutes, respectively. This is the first study where the ionization terms
      for weakly acidic solutes and weakly basic solutes have been separated. LSER
      results obtained with the expanded solute set with and without the inclusion of
      the D(+) and D(-) solute descriptors were compared. The improved correlation and
      standard error obtained for the expanded test set in the presence and absence of
      the D(+) and D(-) descriptors (R(2): 0.987 vs 0.846; SE: 0.051 vs 0.163 for 60%
      MeOH) support inclusion of these additional terms. Further, the coefficients
      obtained from the multiple linear regression for the expanded test set with the
      D(+) and D(-) descriptors were more consistent with the coefficients obtained
      when the test set included just neutral analytes. In addition, the expanded LSER
      model did a better job of predicting elution order for the ionizable analytes.
      This work provides further supporting evidence for the multimodal nature of the
      butylimidazolium stationary phase.

PMID- 21168848
TI  - Determination of acrolein in french fries by solid-phase microextraction gas
      chromatography and mass spectrometry.
AB  - The frying of foods in the home can be a cause of indoor pollution due to the
      formation of acrolein. The emission of acrolein formed during frying in soybean,
      corn, canola, sunflower and palm oils was studied. A GC/MS method has been
      developed to determine acrolein in French fries using SPME as the sampling
      technique after derivatization with 2,4-dinitrophenylhydrazine (DNPH). Optimum
      SPME conditions included desorption at 250 degrees C for 2min after an adsorption
      time of 10min at room temperature. The method presented good resolution,
      repeatability, detection and quantification limits, and linearity of response.
      French fries were prepared in five different oils with four frying steps. The
      results showed that changes in acrolein concentration occurred after frying
      potatoes in different types of oil and at different frying cycles. Potatoes fried
      in soybean oil contained the lowest concentration of acrolein. Shoestring
      potatoes contained a lower concentration of acrolein than potato chips and French
      fries, respectively, because of the higher surface/volume ratio.

PMID- 21168849
TI  - Reversed-phase liquid chromatography/electrospray ionization/mass spectrometry
      with isotope dilution for the analysis of nitrate and nitrite in water.
AB  - A new method was developed for the analysis of nitrate and nitrite in a variety
      of water matrices by using reversed-phase liquid chromatography/electrospray
      ionization/mass spectrometry in the negative ion mode. For this direct analysis
      method, nitrate and nitrite anions were well separated under the optimized LC
      conditions, detected by monitoring m/z 62 and m/z 46 ions, and quantitated by
      using an isotope dilution technique that utilized the isotopically labeled
      analogs. The method sensitivity, accuracy, and precision were investigated, along
      with matrix effects resulting from common inorganic matrix anions. The isotope
      dilution technique, along with sample pretreatment using barium, silver, and
      hydrogen cartridges, effectively compensated for the ionization suppression
      caused by the major water matrix anions, including chloride, sulfate, phosphate,
      and carbonate. The method detection limits, based on seven reagent water
      replicates fortified at 0.01 mg N/L nitrate and 0.1 mg N/L nitrite, were 0.001 mg
      N/L for nitrate and 0.012-0.014 mg N/L for nitrite. The mean recoveries from the
      replicate fortified reagent water and lab water samples containing the major
      water matrix anions, were 92-103% for nitrate with an imprecision (relative
      standard deviation, RSD) of 0.4-2.1% and 92-110% for nitrite with an RSD of 1.1
      4.4%. For the analysis of nitrate and nitrite in drinking water, surface water,
      and groundwater samples, the obtained results were generally consistent with
      those obtained from the reference methods. The mean recoveries from the replicate
      matrix spikes were 92-123% for nitrate with an RSD of 0.6-7.7% and 105-113% for
      nitrite with an RSD of 0.3-1.8%.

PMID- 21168850
TI  - New phosphorus-containing spherical carbon adsorbents as promising materials in
      drug adsorption and release.
AB  - A simple method of preparation of new high surface area spherical carbon
      adsorbents is presented. The phosphoric acid activation upon hydrothermally
      formed spherules was employed to produce carbons having controlled high specific
      surface area (over 2100m(2)/g), large volumes of pores (1.2cm(3)/g), and high
      acidity. Prepared from sucrose materials show high adsorption capacities (i.e.
      220mg/g(C)) toward paracetamol. It is proved that for these materials the
      contents of surface phosphorus are responsible for the reversibility of drug
      adsorption/release process.

PMID- 21168851
TI  - Porcine circovirus-2 viral load versus lesions in pigs: perspectives for post
      weaning multisystemic wasting syndrome.
AB  - Porcine circovirus-2 (PCV-2) is the main agent related to post-weaning
      multisystemic wasting syndrome (PMWS) and it is also associated with other
      syndromes affecting pigs. Not all pigs infected with PCV-2 will develop PMWS and
      the incidence of PMWS is higher when coinfecting viral and bacterial pathogens
      are present. In this study, PCV-2 viral loads were evaluated in the tissues of
      animals with and without PMWS in order to investigate the relationship between
      viral load and microscopical lesions. Lymph nodes had the highest average viral
      load, but there was no significant difference between lesion severity and the
      viral load in these structures. There was no significant difference between the
      average viral load in inguinal lymph nodes of animals with and without PMWS.
      However, samples from pigs with PMWS had more severe lesions compared with
      samples from non-PMWS animals. These findings suggest that other infectious and
      non-infectious cofactors may be important in the pathogenesis of PMWS.

PMID- 21168852
TI  - Ventricular tachycardia storm terminated by intracoronary contrast injection.
AB  - We describe the case of an 85-year-old man who developed incessant ventricular
      tachycardia despite multiple medical interventions. During diagnostic coronary
      angiography, a single contrast injection into his right coronary artery abruptly
      terminated the ventricular tachycardia.

PMID- 21168853
TI  - Fluconazole prophylaxis in extremely low birth weight infants and
      neurodevelopmental outcomes and quality of life at 8 to 10 years of age.
AB  - OBJECTIVE: To examine the long-term effects of fluconazole prophylaxis in
      extremely low birth weight infants. STUDY DESIGN: Neurodevelopmental status and
      quality of life of survivors from a randomized, placebo-controlled trial of
      fluconazole prophylaxis were evaluated at 8 to 10 years of life using the
      Vineland Adaptive Behavior Scales-II (VABS-II) and the Child Health Questionnaire
      Parent-Completed Form 28 (CHQ-PF28), respectively. RESULTS: VABS-II Domain Scores
      for the fluconazole-treated (n = 21; 9.1 +/- 0.7 years) compared with the placebo
      group (n = 17; 9.3 +/- 0.8 years) were similar for communication [94.6 (+/-14.8)
      versus 92.6 (+/-12.6), P = .65], daily living skills [87.9 (+/-10.6) versus 87.4
      (+/-9.3), P = .89], socialization [97.2 (+/-9.2) versus 94.4 (+/-7.9), P = .31],
      and motor skills [92.1 (+/-17.8) versus 95.1 (+/-14.6), P = .57]. Internalizing
      and externalizing behaviors and maladaptive behavior index were also similar. The
      CHQ-PF28 revealed no differences between the two groups regarding quality of
      life. Survivors were also happy or satisfied with school (90% versus 100%, P =
      .49), friendships (90% versus 88%, P = 1.00), and life (95% versus 100%, P =
      1.00). Self esteem scores were 87.3 +/- 15.7 versus 89.7 +/- 10.4 (P = .59).
      There were also no differences between groups regarding emotional difficulties or
      behavior problems. CONCLUSIONS: Fluconazole prophylaxis for the prevention of
      invasive Candida infections is safe in extremely low birth weight infants and
      does not appear to be associated with any long-term adverse effects on
      neurodevelopment and quality of life at 8 to 10 years of life.

PMID- 21168854
TI  - Human interleukin-10 genotypes are associated with different precore/core gene
      mutation patterns in children with chronic hepatitis B virus infection.
AB  - OBJECTIVE: To elucidate the association between human interleukin-10 (IL-10)
      genotypes and hepatitis B virus (HBV) precore/core gene mutation in children with
      chronic HBV infection. STUDY DESIGN: The study group comprised of 21 children
      with chronic HBV infection with spontaneous hepatitis B e antigen (HBeAg)
      seroconversion who were followed for more than 10 years. Another nine children
      without HBeAg seroconversion served as the control subjects. Sera at the immune
      tolerance and inflammatory phase (alanine aminotransferase, >80 IU/L) were
      subjected to HBV precore/core sequence analysis. IL-10 -1082 polymorphism was
      also determined. RESULTS: HBV precore/core gene mutation increased significantly
      more in the inflammatory phase than in the tolerance phase (G1896A, 76.2% versus
      4.8%; C1913A, 33.3% versus 0%; C2189A, 28.6% versus 4.8%; G2304A, 52.4% versus
      14.3%) in study group (n = 21) but not the control group (n = 9). Subjects with
      the G/G genotype at the IL-10-1082 polymorphism site had higher C2189A mutation
      rate than the A allele carriers (P = .02). C2189A mutation carriers are
      associated with more viral load decrement from tolerance to inflammatory phase (P
      = .01) and earlier spontaneous HBeAg seroconversion (P = .01). CONCLUSIONS: The
      G/G genotype at the IL-10 -1082 polymorphism is associated with higher C2189A
      mutations, lower HBV viral load at immune inflammatory phase, and earlier
      spontaneous HBeAg seroconversion than A allele carriers.

PMID- 21168856
TI  - Inhibin B and anti-Mullerian hormone as markers of gonadal function after
      treatment for medulloblastoma or posterior fossa ependymoma during childhood.
AB  - OBJECTIVE: To evaluate the roles of hypothalamic-pituitary and spinal
      irradiations and chemotherapy in gonadal deficiency after treatment for
      medulloblastoma or posterior fossa ependymoma by measuring levels of plasma
      inhibin B and antimullerian hormone (AMH). STUDY DESIGN: A total of 34 boys and
      22 girls were classified as having normal levels of plasma follicle-stimulating
      hormone (FSH; <9 IU/L), or abnormal levels of FSH (>9 IU/L) and luteinizing
      hormone (LH; <5 or >5 IUL). RESULTS: Two boys had partial gonadotropin
      deficiency, combined with testicular deficiency in one boy. Six boys had
      increased levels of FSH, indicating tubular deficiency, combined with Leydig cell
      deficiency in 5 boys. The 7 boys with inhibin B levels <100 ng/mL included the
      one with combined deficiencies and the 6 with testicular deficiency. Puberty did
      not progress in 7 girls; 3 had gonadotropin deficiency, combined with ovarian
      deficiency in one, and 4 had increased FSH levels, indicating ovarian deficiency.
      Inhibin B and AMH levels were low in the girl with combined deficiencies, in the
      4 girls with ovarian deficiency, and in 4 girls with normal clinical-biological
      ovarian function, including 2 who underwent ovarian transposition before
      irradiation. CONCLUSION: The plasma concentrations of inhibin B and AMH are
      useful means of detecting primary gonad deficiency in patients with no increase
      in their plasma gonadotropin levels because of radiation-induced gonadotropin
      deficiency.

PMID- 21168855
TI  - Functional brown adipose tissue is related to muscle volume in children and
      adolescents.
AB  - OBJECTIVE: We examined whether the depiction of brown adipose tissue (BAT) with
      positron emission tomography/computed tomography (PET/CT) in pediatric patients
      is associated with anthropometric measures. STUDY DESIGN: We determined measures
      of body mass, adiposity, and musculature in 71 children and adolescents who
      underwent PET/CT examinations and compared patients with and without BAT. We used
      regression analyses to assess the relation between BAT and anthropometric
      measures. RESULTS: A total of 30 patients (42%) had BAT depicted on PET/CT, 10 of
      26 girls (38%) and 20 of 45 boys (44%). Compared with patients without functional
      BAT, patients with BAT had significantly greater neck musculature (1880 +/- 908
      cm(3) versus 1299 +/- 806 cm(3); P = .028 for boys and 1295 +/- 586 cm(3) versus
      854 +/- 392 cm(3); P = .030 for girls) and gluteus musculature (1359 +/- 373
      cm(3) versus 1061 +/- 500 cm(3); P = .032 for boys and 1138 +/- 425 cm(3) versus
      827 +/- 297 cm(3); P = .038 for girls), but no differences in age, body mass
      index, or measures of subcutaneous fat. With logistic regression analyses, neck
      and pelvic musculature predicted the presence of BAT independently of age, sex,
      body size, and season of scan (P = .018 and .009, respectively). CONCLUSION:
      Pediatric patients with visualized BAT on PET/CT examinations had significantly
      greater muscle volume than patients with no visualized BAT.

PMID- 21168858
TI  - Controlled hyperkalemic reperfusion with magnesium rescues ischemic juvenile
      hearts by reducing calcium loading.
AB  - OBJECTIVES: Our objectives were (1) to determine whether elevated Mg(2+) in
      controlled hyperkalemic reperfusate without intervention during ischemia protects
      the juvenile heart against reperfusion injury; and (2) to identify the
      mechanism(s) underlying any protective effect of Mg(2+). METHODS: Langendorff
      perfused hearts from juvenile (11- to 14-day-old) guinea pigs were subjected to
      mild (30-minute) or severe (45-minute) normothermic global ischemia and 35-minute
      reperfusion. Hearts were subjected to controlled hyperkalemic reperfusion without
      or with various concentrations of Mg(2+) (5, 10, 16, 23 mM). The mechanisms
      underlying the effect of Mg(2+) on intracellular Ca(2+) ([Ca(2+)]i) were also
      studied in isolated cardiomyocytes exposed to metabolic inhibition followed by
      washout using hyperkalemic solutions (reperfusion). RESULTS: Sixteen mM Mg(2+)
      conferred maximal cardioprotection as assessed by improved functional recovery
      and reduced cardiac injury; this was associated with a significant recovery of
      cardiac energetics and metabolism following both mild and severe ischemia. The
      Mg(2+)-induced protection was additive to that of hyperkalemia following mild
      ischemia and conferred protection following severe ischemia when hyperkalemia
      alone had no significant effect. Elevated Mg(2+) in the hyperkalemic reperfusate
      of cardiomyocytes acutely prevented [Ca(2+)]i loading following mild metabolic
      inhibition and augmented the fall in [Ca(2+)]i following severe metabolic
      inhibition. CONCLUSIONS: This work demonstrates for the first time in juvenile
      hearts that elevated Mg(2+) during controlled hyperkalemic reperfusion rescues
      the heart following ischemia, and that this is likely to be facilitated by
      reducing [Ca(2+)]i which, in turn, would aid metabolic recovery.

PMID- 21168859
TI  - Learning curve analysis of mitral valve repair using telemanipulative technology.
AB  - OBJECTIVE: To determine if the time required to perform mitral valve repairs
      using telemanipulation technology decreases with experience and how that decrease
      is influenced by patient and procedure variables. METHODS: A single-center
      retrospective review was conducted using perioperative and outcomes data
      collected contemporaneously on 458 mitral valve repair surgeries using
      telemanipulative technology. A regression model was constructed to assess
      learning with this technology and predict total robot time using multiple
      predictive variables. Statistical analysis was used to determine if models were
      significantly useful, to rule out correlation between predictor variables, and to
      identify terms that did not contribute to the prediction of total robot time.
      RESULTS: We found a statistically significant learning curve (P < .01). The
      institutional learning percentage* derived from total robot times? for the first
      458 recorded cases of mitral valve repair using telemanipulative technology is
      95% (R(2) = .40). More than one third of the variability in total robot time can
      be explained through our model using the following variables: type of repair
      (chordal procedures, ablations, and leaflet resections), band size, use of clips
      alone in band implantation, and the presence of a fellow at bedside (P < .01).
      CONCLUSIONS: Learning in mitral valve repair surgery using telemanipulative
      technology occurs at the East Carolina Heart Institute according to a logarithmic
      curve, with a learning percentage of 95%. From our regression output, we can make
      an approximate prediction of total robot time using an additive model. These
      metrics can be used by programs for benchmarking to manage the implementation of
      this new technology, as well as for capacity planning, scheduling, and capital
      budget analysis.

PMID- 21168860
TI  - Multiple pudendal sensory pathways reflexly modulate bladder and urethral
      activity in patients with spinal cord injury.
AB  - PURPOSE: Electrical stimulation of pudendal afferents can evoke reflex bladder
      contractions with relaxation of the external urethral sphincter in cats. This
      voiding reflex is mediated by pudendal sensory fibers innervating the penile and
      prostatic urethra that engage spinal and spinobulbospinal micturition pathways,
      respectively. However, clinical translation of this potential therapy in
      individuals with spinal cord injury is limited by the lack of evidence showing
      analogous reflex mechanisms in humans. We investigated excitatory pudendal-to
      bladder reflexes in 7 individuals with chronic spinal cord injury. MATERIALS AND
      METHODS: We recorded isovolumetric bladder pressure and perineal electromyogram
      in response to intraurethral electrical stimulation at varying amplitudes and
      frequencies. RESULTS: Selective electrical stimulation of the proximal (29.7 +/-
      11.6 cm H(2)O) and distal urethral (23.3 +/- 9.28 cm H(2)O) segments evoked
      sustained reflex bladder contractions in different subsets (3 each) of
      participants. In contrast, the corresponding reflex perineal electromyogram
      revealed a differential activation pattern between proximal and distal
      intraurethral stimulation (normalized electromyogram of 1.3 +/- 0.2 and 0.3 +/-
      0.1, respectively, p <0.05). CONCLUSIONS: To our knowledge we report the first
      clinical evidence of 2 independent excitatory pudendal-to-bladder reflex
      pathways, which in turn differentially modulate efferent pudendal output. Each
      reflex mechanism involves complex interaction of multiple sensory inputs and may
      provide a neural substrate to restore micturition after spinal cord injury.

PMID- 21168857
TI  - Evaluation of Kawasaki disease risk-scoring systems for intravenous
      immunoglobulin resistance.
AB  - OBJECTIVES: To assess the performance of 3 risk scores from Japan that were
      developed to predict, in children with Kawasaki disease, resistance to
      intravenous immunoglobulin (IVIG) treatment. STUDY DESIGN: We used data from a
      randomized trial of pulsed steroids for primary treatment of Kawasaki disease to
      assess operating characteristics of the 3 risk scores, and we examined whether
      steroid therapy lowers the risk of coronary artery abnormalities in patients
      prospectively classified as IVIG resistant. RESULTS: For comparability with
      published cohorts, we analyzed the data of 99 patients who were not treated with
      steroids (16% IVIG-retreated) and identified male sex, lower albumin level, and
      higher aspartate aminotransferase level as independent risk factors for IVIG
      resistance. The Kobayashi score was similar in IVIG-resistant and -responsive
      patients, yielding a sensitivity of 33% and specificity of 87%. There was no
      interaction of high-risk versus low-risk status by treatment received (steroid
      versus placebo) with any of the 3 risk score algorithms. CONCLUSION: Risk-scoring
      systems from Japan have good specificity but low sensitivity for predicting IVIG
      resistance in a North American cohort. Primary steroid therapy did not improve
      coronary outcomes in patients prospectively classified as being at high-risk for
      IVIG resistance.

PMID- 21168861
TI  - Receptor heterodimerization: a new mechanism for platelet-derived growth factor
      induced resistance to anti-epidermal growth factor receptor therapy for bladder
      cancer.
AB  - PURPOSE: Human bladder cancer cells resistant to anti-epidermal growth factor
      receptor therapy often co-express platelet-derived growth factor receptor-beta.
      We determined whether there is functional crosstalk between epidermal growth
      factor receptor and platelet-derived growth factor receptor-beta, and how this
      regulates biological functions in bladder cancer cases. MATERIALS AND METHODS: We
      determined heterodimerization and co-localization of epidermal growth factor
      receptor and platelet-derived growth factor receptor-beta by immunoprecipitation
      and confocal microscopy, respectively. We tested the antiproliferative effects of
      specific inhibitory monoclonal antibodies to each receptor by (3)H-thymidine
      uptake assay. We transfected the nonplatelet-derived growth factor receptor-beta
      expressing bladder cancer cell line UMUC5 with the platelet-derived growth factor
      receptor-beta gene. These cells were analyzed in vitro by (3)H-thymidine uptake
      and by MatrigelTM invasion assay, and in vivo for tumorigenicity, metastatic
      potential and orthotopic growth. In a treatment study nude mice were inoculated
      with orthotopic tumors and treated with the inhibitory antibodies alone and in
      combination. RESULTS: Immunoprecipitation revealed epidermal growth factor
      receptor/platelet-derived growth factor receptor-beta heterodimers in all
      platelet-derived growth factor receptor-beta expressing cell lines. Forced
      expression of platelet-derived growth factor receptor-beta in epidermal growth
      factor receptor sensitive UMUC5 cells (50% inhibitory concentration less than 10
      nM) significantly decreased responsiveness to epidermal growth factor receptor
      inhibition (50% inhibitory concentration greater than 100 nM) and increased
      invasive potential 3-fold as well as tumorigenicity. Increased invasiveness was
      associated with epidermal growth factor triggered platelet-derived growth factor
      receptor-beta transactivation, increased mitogen activated protein kinase and
      glycogen synthase kinase-3beta phosphorylation, and decreased E-cadherin.
      Inhibition of epidermal growth factor receptor and platelet-derived growth factor
      receptor-beta receptors blocked cell invasion, decreased cell proliferation,
      reduced xenograft tumor growth and increased E-cadherin expression. CONCLUSIONS:
      In epidermal growth factor receptor expressing bladder cancer co-expression of
      platelet-derived growth factor receptor-beta has implications for tumor biology.
      Thus, it should be further evaluated as a strategy involving dual receptor
      targeting.

PMID- 21168862
TI  - The gatekeeper disparity--why do some medical schools send more medical students
      into urology?
AB  - PURPOSE: Urology continues to be a highly desirable specialty despite decreasing
      exposure of students to urology in American medical schools. We assessed how
      American medical schools compare to each other in regard to the number of
      students that each sends into urological training. We evaluated the reasons why
      some medical schools consistently send more students into urology than others.
      MATERIALS AND METHODS: We obtained American Urological Association Match data for
      the 5 match seasons from 2005 to 2009. We then surveyed all successful
      participants. The survey instrument was designed to determine what aspects of the
      medical school experience influenced students to specialize in urology. Bivariate
      and multivariate analysis was then done to assess which factors correlated with
      more students entering urology from a particular medical school. RESULTS: Between
      2005 and 2009 a total of 1,149 medical students from 130 medical schools
      successfully participated in the urology match. Of the 132 allopathic medical
      schools 128 sent at least 1 student into urology (mean +/- SD 8.9 +/- 6.5, median
      8). A few medical schools were remarkable outliers, sending significantly more
      students into urology than other institutions. Multivariate analysis revealed
      that a number of medical school related variables, including strong mentorship,
      medical school ranking and medical school size, correlated with more medical
      students entering urology. CONCLUSIONS: Some medical schools launch more
      urological careers than others. Although the reasons for these findings are
      multifactorial, recruitment of urological talent pivots on these realities.

PMID- 21168863
TI  - Urology resident publication output and its relationship to future academic
      achievement.
AB  - PURPOSE: Scholarly research is considered by many to be an important component of
      residency training but little is known about the quantity and types of
      publications produced by urology residents. To our knowledge whether publication
      efforts during residency predict future academic publication performance is also
      unknown. We evaluated resident productivity, as measured by peer reviewed
      publication output, and determined its relation to future publication output as
      junior faculty. MATERIALS AND METHODS: We assembled a list of graduating
      residents from 2002 to 2004 who were affiliated with the top 50 urology
      hospitals, as ranked in 2009 by U.S. News&World Report. PubMed(r) was queried to
      determine the publication total in the last 3 years of residency of each
      individual and during years 2 to 4 after residency graduation. Resident
      publication output was stratified by research time and fellowship training. The
      relationship between resident productivity and future achievement was assessed.
      RESULTS: We assessed the publication output of 251 urologists from a total of 34
      training programs affiliated with the top 50 urology hospitals. Subjects
      published a mean total of 3.5 and a mean of 2.0 first author papers during
      training. Greater research time during residency was associated with increased
      productivity during and after residency. Publication during training correlated
      with publication during the early academic career. CONCLUSIONS: Publication
      output correlated with increasing dedicated research time and was associated with
      the pursuit of fellowship training and an academic career. Publication during
      residency predicted future academic achievement.

PMID- 21168864
TI  - Cannabinor, a selective cannabinoid-2 receptor agonist, improves bladder emptying
      in rats with partial urethral obstruction.
AB  - PURPOSE: We studied the effects of chronic treatment with the novel selective
      cannabinoid 2 receptor agonist cannabinor (Procter & Gamble Pharmaceuticals,
      Cincinnati, Ohio) on bladder function in conscious rats with partial urethral
      obstruction and on the functional properties of isolated detrusor muscle.
      MATERIALS AND METHODS: A total of 24 female Sprague-Dawley(r) rats with
      surgically created partial urethral obstruction received daily intraperitoneal
      injections of 3 mg/kg cannabinor (12) or saline as controls (12) for 2 weeks.
      Cystometry was done, the rats were sacrificed and the bladders were prepared for
      in vitro studies. RESULTS: Mean +/- SEM bladder weight was 0.97 +/- 0.15 gm in
      controls and 0.53 +/- 0.08 gm in cannabinor treated rats (p <0.05). There was no
      difference between the groups in the mean micturition interval, or mean baseline,
      threshold, flow or maximum pressure. In controls and cannabinor treated rats mean
      post-void residual volume was 0.28 +/- 0.07 and 0.06 +/- 0.02 ml, mean
      micturition compliance was 0.032 +/- 0.006 and 0.069 +/- 0.016 ml/cm H(2)O, and
      mean bladder wall force at the start of flow was 950 +/- 280 and 1,647 +/- 325
      mN/gm, respectively (each p <0.05). Nonvoiding contractions were significantly
      less frequent in cannabinor treated rats than in controls. We noted no difference
      in carbachol (Sigma(r)) half maximum concentration between the groups but the
      carbachol maximum response in detrusor strips from cannabinor treated rats was
      significantly higher than that in control strips. CONCLUSIONS: In rats with
      partial urethral obstruction treated daily for 14 days with cannabinor bladder
      weight was lower, the ability to empty the bladder was preserved and nonvoiding
      contraction frequency was low compared to those in controls. Detrusor
      preparations from cannabinor treated rats showed a higher response to nerve
      stimulation than those from controls. Selective cannabinoid 2 receptor activation
      may be a novel principle to enable improved bladder function after partial
      urethral obstruction.

PMID- 21168865
TI  - Is the screening method of sacral neuromodulation a prognostic factor for long
      term success?
AB  - PURPOSE: We evaluated whether there is a difference in long-term outcomes between
      patients screened with percutaneous nerve evaluation and a first stage tined lead
      procedure. We also evaluated the outcome in patients who only responded to
      screening with the tined lead procedure after failed initial percutaneous nerve
      evaluation. MATERIALS AND METHODS: We evaluated all patients screened for
      eligibility to receive sacral neuromodulation treatment since the introduction of
      the tined lead technique in our center in 2002. In May 2009 all implanted
      patients were asked to maintain a voiding diary to record the effect of sacral
      neuromodulation on urinary symptoms. Chi-square analysis was used to evaluate
      differences in the long-term outcomes of the separate screening methods. RESULTS:
      A total of 92 patients were screened for sacral neuromodulation. Of the 76
      patients screened with percutaneous nerve evaluation 35 (46%) met the criteria
      for permanent implantation. In 11 of the 16 patients (69%) who underwent direct
      screening with the tined lead procedure permanent stimulators were placed. Of the
      41 patients in whom percutaneous nerve evaluation failed and who subsequently
      underwent screening with tined lead procedure 18 (44%) were implanted with a
      neurostimulator after a successful response. Statistical analysis showed no
      difference between screening type and long-term success (p = 0.94). CONCLUSIONS:
      The first stage tined lead procedure is a more sensitive screening tool than
      percutaneous nerve evaluation but long-term success seems to be independent of
      the screening method. Patients in whom percutaneous nerve evaluation initially
      failed but who responded to prolonged screening the with tined lead procedure
      appeared to be as successful as those who directly responded to percutaneous
      nerve evaluation or the tined lead procedure.

PMID- 21168866
TI  - Functional detrusor myoplasty for bladder acontractility: long-term results.
AB  - PURPOSE: We present the long-term results of a multicenter investigation with
      latissimus dorsi detrusor myoplasty in patients with bladder acontractility
      caused by lower motor neuron lesion in whom there is no treatment alternative
      other than lifelong clean intermittent catheterization. MATERIALS AND METHODS:
      From 2001 to 2008, 24 patients (median age 39 years, range 13 to 63, 16 males, 8
      females) requiring complete clean intermittent catheterization 4 to 7 times daily
      underwent latissimus dorsi detrusor myoplasty at 4 centers worldwide. Before the
      procedure patients were on clean intermittent catheterization for a median of 55
      months (range 17 to 195). Median followup was 46 months (range 8 to 89) and was
      performed by urodynamics and measurement of post-void residual urine volume.
      Bladder contractility index was calculated. The t test was used for statistical
      analysis. RESULTS: Of the 24 patients 17 (71%) gained complete spontaneous
      voiding with a mean post-void residual urine volume of 25 ml (range 0 to 100).
      Mean bladder contractility index increased from 20.1 +/- 7.6 to 176.2 +/- 25.4 (p
      <0.001). In 3 patients (13%) the frequency of clean intermittent catheterization
      was reduced to 2 to 4 times daily with a mean post-void residual urine volume of
      200 ml (range 150 to 250). Mean bladder contractility index was 12.0 +/- 7.2
      preoperatively and 68.7 +/- 28.1 postoperatively (p = 0.12). Recurrent urinary
      tract infections (defined as the presence of clinical symptoms such as dysuria
      and fever, and microbiological evidence of germs) ceased in 21 of 23 patients
      (91%, mean preoperatively 8 per year). Four patients (17%) required clean
      intermittent catheterization with the same frequency as before the procedure
      (mean bladder contractility index preoperatively 22.5 +/- 10.3 and
      postoperatively 26.0 +/- 12.3, p = 0.83). No chronic pain at the donor site or
      vesicoureteral reflux was observed in any patient. CONCLUSIONS: The results of
      this multicenter analysis demonstrate that latissimus dorsi detrusor myoplasty is
      an effective alternative to clean intermittent catheterization in a select group
      of patients with neurogenic bladder acontractility.

PMID- 21168867
TI  - Long-term complications of conduit urinary diversion.
AB  - PURPOSE: We evaluated long-term surgical complications and clinical outcomes in a
      large group of patients treated with conduit urinary diversion. MATERIALS AND
      METHODS: We identified 1,057 patients who underwent radical cystectomy with
      conduit urinary diversion using ileum or colon at our institution from 1980 to
      1998 with complete followup information. Patients were followed for long-term
      clinical outcomes and analyzed for the incidence of diversion specific
      complications. RESULTS: A total of 844 patients died at a median of 4.1 years
      (range 0.1 to 28.1) following cystectomy. Median followup of the surviving 213
      patients was 15.5 years (range 0.3 to 29.1). There were 643 (60.8%) patients with
      1,453 complications directly attributable to the urinary diversion performed with
      a mean of 2.3 complications per patient. Bowel complications were the most
      common, occurring in 215 patients (20.3%), followed by renal complications in 213
      (20.2%), infectious complications in 174 (16.5%), stomal complications in 163
      (15.4%) and urolithiasis in 162 (15.3%). The least common were metabolic
      abnormalities, which occurred in 135 patients (12.8%), and structural
      complications, which occurred in 122 (11.5%). Increasing age at cystectomy (HR
      1.21, p <0.001), increasing Eastern Cooperative Oncology Group performance status
      (HR 1.23, p = 0.02) and recent era of surgery (HR 1.68, p <0.001) were
      significantly associated with a higher incidence of complications. CONCLUSIONS:
      Conduit urinary diversion is associated with a high overall complication rate but
      a low reoperation rate. Long-term followup of these patients is necessary to
      closely monitor for potential complications from the urinary diversion that can
      occur decades later.

PMID- 21168868
TI  - The impact of proximal stone burden on the management of encrusted and retained
      ureteral stents.
AB  - PURPOSE: Managing the encrusted and retained ureteral stent is a potentially
      complex challenge. To improve surgical planning, we hypothesized that proximal
      stone burden is the most important factor associated with complicated removal,
      and that computerized tomography more accurately estimates stone burden than
      plain film x-ray of the kidneys, ureters and bladder. MATERIALS AND METHODS:
      Records were reviewed of patients undergoing surgical removal of an encrusted and
      retained ureteral stent or nephrostomy at Ben Taub General Hospital from 2007 to
      2009. Preoperative imaging consisted of a plain x-ray of the kidneys, ureters and
      bladder and/or computerized tomography of the abdomen/pelvis. Each encrusted tube
      was assessed using the FECal (forgotten, encrusted, calcified) grading system and
      associated stone burden was calculated. Univariate and multivariate analyses were
      performed to determine factors associated with the need for multiple surgeries.
      RESULTS: A total of 55 encrusted and retained ureteral stents and 1 nephrostomy
      were removed from 52 patients. Mean tube duration was 24.9 months. Most tubes
      were removed endoscopically (94.2%). Of the patients 21.2% required multiple
      surgical procedures to remove each tube. Computerized tomography graded stone
      burden more accurately than plain x-ray of the kidneys, ureters and bladder
      (94.9% vs 64.4%, p = 0.01). Plain x-ray of the kidneys, ureters and bladder
      underestimated proximal stone burden in 44.4% of patients who underwent multiple
      surgeries. When dividing stone burden into 3 categories (0 to 100, 101 to 400 and
      greater than 401 mm(2)) only proximal stone burden correlated with multiple
      surgeries and surgical complications (p = 0.01 for both). On multivariate
      analysis only proximal stone burden was associated with multiple surgeries to
      remove each tube (OR 12.1, 95% CI 1.5-95.9, p = 0.02 for 101 to 400 mm(2) and OR
      18.1, 95% CI 1.7-192.8, p = 0.02 for greater than 401 mm(2)). CONCLUSIONS: In
      patients with encrusted and retained ureteral stents accurate determination of
      the proximal stone burden, preferably by computerized tomography, is important
      for surgical counseling and planning.

PMID- 21168869
TI  - Overprescription of postoperative narcotics: a look at postoperative pain
      medication delivery, consumption and disposal in urological practice.
AB  - PURPOSE: Prescription narcotic abuse is a significant social problem. Surplus
      medication following surgery is 1 source of prescription diversion. We assessed
      prescribing practices, consumption and disposal of prescribed narcotics after
      urological surgery. MATERIALS AND METHODS: Surveys were administered to a 3-month
      consecutive sample of adult patients who underwent surgery performed by full and
      adjunct University of Utah Urology faculty. Surveys were performed 2 to 4 weeks
      postoperatively. With the exception of the investigators, prescribing physicians
      had no prior knowledge of the study. Data collected included perception of pain
      control, type and quantity of medication prescribed, quantity of leftover
      medication, refills needed, disposal instructions and surplus medication
      disposition. RESULTS: Overall 47% of 586 patients participated in the study.
      Hydrocodone was prescribed most commonly (63%), followed by oxycodone (35%), and
      86% of the patients were satisfied with pain control. Of the dispensed narcotics
      58% was consumed and 12% of patients requested refills. A total of 67% of
      patients had surplus medication from the initial prescription and 92% received no
      disposal instructions for surplus medication. Of those patients with leftover
      medication 91% kept the medication at home while 6% threw it in the trash, 2%
      flushed it down the toilet and less than 1% returned it to a pharmacy.
      CONCLUSIONS: Overprescription of narcotics is common and retained surplus
      medication presents a readily available source of opioid diversion. It appears
      that no entity on the prescribing or dispensing ends of prescription opioid
      delivery is fulfilling the responsibility to accurately educate patients on
      proper surplus medication disposal. Surgeons should analyze prescribing practices
      and consider decreasing the quantity of postoperative narcotics prescribed.

PMID- 21168870
TI  - Long-term infection outcomes after original antibiotic impregnated inflatable
      penile prosthesis implants: up to 7.7 years of followup.
AB  - PURPOSE: Although some studies suggest that most infections associated with
      inflatable penile prosthesis implantation develop within year 1 after surgery,
      device related infections have been reported 5 years after implantation or later
      and the infection risk with time is not well characterized. We previously
      reported a statistically significantly lower infection rate for original
      inflatable penile prostheses impregnated with antibiotic treatment with
      minocycline and rifampin vs nonimpregnated inflatable penile prostheses at 1-year
      followup. Long-term data are now available on infection revision after initial
      implantation of antibiotic impregnated vs nonimpregnated prostheses. MATERIALS
      AND METHODS: We retrospectively reviewed patient information forms voluntarily
      filed with the manufacturer after the initial implantation of more than 39,000
      inflatable penile prostheses to compare the revision rate due to infection for
      antibiotic impregnated vs nonimpregnated implants between May 1, 2001 and
      December 31, 2008. Life table analysis was used to evaluate device survival from
      revision surgery. RESULTS: On life table survival analysis initial revision
      events due to infection were significantly less common in the impregnated vs the
      nonimpregnated group (log rank p <0.0001). At up to 7.7 years of followup 1.1% of
      35,737 vs 2.5% of 3,268 men with impregnated vs nonimpregnated implants underwent
      initial revision due to infection. CONCLUSIONS: To our knowledge this long-term
      outcome analysis provides the first substantial clinical evidence of a decrease
      in costly infection related revision using an antibiotic impregnated inflatable
      penile prosthesis.

PMID- 21168872
TI  - Current outcome of patients with ureteral stents for the management of malignant
      ureteral obstruction.
AB  - PURPOSE: We analyzed the prognostic factors associated with overall survival and
      predictive factors of stent failure in patients treated with an indwelling
      retrograde ureteral stent for malignant ureteral obstruction. MATERIALS AND
      METHODS: Among 186 Japanese patients treated with an indwelling retrograde
      ureteral stent for ureteral obstruction from January 2005 to March 2010, 61 with
      malignant ureteral obstruction and 95 ureteral units were analyzed
      retrospectively. RESULTS: Median survival was estimated at 228 days. Unfavorable
      prognostic factors of overall survival were no treatment after indwelling
      retrograde ureteral stent placement (p = 0.023) and a serum creatinine before
      indwelling retrograde ureteral stent placement of 1.2 mg/dl or greater (p =
      0.016). Overall survival differed significantly among cancer groups (p <0.001) as
      did stent failure-free survival (p = 0.011). Overall survival differed
      significantly among 3 risk groups divided according to the score calculated with
      regard to prognostic factors (p <0.001). CONCLUSIONS: Gynecologic cancer was a
      significant favorable predictor of stent failure-free survival. Patients treated
      with an indwelling retrograde ureteral stent for malignant ureteral obstruction
      were divided into 3 groups, which showed significant differences in overall
      survival. This risk classification may help urologists predict survival time.

PMID- 21168871
TI  - Size does matter: donor renal volume predicts recipient function following live
      donor renal transplantation.
AB  - PURPOSE: With the now routine use of computerized tomography angiography with 3
      dimensional reconstruction in the donor evaluation, renal volume can be easily
      determined using volume calculating software. We evaluated whether donor renal
      volume could predict recipient renal function. MATERIALS AND METHODS: Clinical
      data of all donor and recipient pairs undergoing live donor kidney
      transplantation at our institution between January 2006 and October 2009 were
      reviewed. The volume of the kidney selected for transplant was determined using
      volume calculating software, and correlated to transplant recipient nadir and 1
      year serum creatinine. Multivariate regression analysis was performed to adjust
      for demographic and clinical variables. RESULTS: During the study period 114
      patients underwent live donor renal transplantation. Recipient nadir and 1-year
      serum creatinine levels were significantly correlated with the volume of donated
      kidney even after adjusting for age, body mass index, body surface area and donor
      creatinine clearance. Kidney volume also retained significance after excluding
      recipients from analysis who experienced acute rejection episodes. CONCLUSIONS:
      Larger kidney volumes calculated using 3-dimensional computerized tomography with
      volume calculating software are correlated with lower recipient nadir and 1-year
      serum creatinine levels.

PMID- 21168873
TI  - Apatite in kidney stones is a molecular composite with glycosaminoglycans and
      proteins: evidence from nuclear magnetic resonance spectroscopy, and relevance to
      Randall's plaque, pathogenesis and prophylaxis.
AB  - PURPOSE: We characterized the biomacromolecular composition of phosphatic urinary
      stones using solid state nuclear magnetic resonance spectroscopy. We identified
      possible parallels between the nature of the organic matrix-mineral interface in
      stones and that in other mineralized tissue using nuclear magnetic resonance
      spectroscopy rotational echo double resonance. MATERIALS AND METHODS: We analyzed
      28 phosphatic (apatite and mixed apatite-struvite) surgically removed stones by
      nuclear magnetic resonance spectroscopy using (31)P, (13)C and a 9.4 Tesla
      magnetic field. Ten samples had sufficient signal from biomacromolecular organic
      material to characterize the mineral/organic interface by (13)C{(31)P} rotational
      echo double resonance. RESULTS: Biomacromolecular organic material was most
      abundant in phosphatic stones in which apatite predominated. Nuclear magnetic
      resonance spectroscopy detected variable proportions of protein,
      glycosaminoglycan, lipid and carbonate. Rotational echo double resonance revealed
      strong interaction between mineral and glycosaminoglycan molecules, and to a
      lesser extent protein molecules, on the sub-nm length scale, implying that
      glycosaminoglycan and protein are composited into or onto the mineral lattice by
      strong physicochemical interactions. Carbonate ions substituted into apatite
      crystal lattices also showed the expected strong (13)C{(31)P} rotational echo
      double resonance effects. Conversely when present, lipid, calcium oxalate
      hydrates and uric acid showed no rotational echo double resonance effects,
      proving that they exist as deposits or crystals distinct from phosphatic
      mineral/biomacromolecular composites. CONCLUSIONS: The intimate coexistence of
      biomacromolecules, especially glycosaminoglycan, with apatite in phosphatic
      stones supports the notion that they may have a key role in stone pathogenesis.
      The underlying intermolecular relationships may reflect those governing the
      formation of Randall's plaque in nascent stones.

PMID- 21168875
TI  - Association of nocturia and mortality: results from the Third National Health and
      Nutrition Examination Survey.
AB  - PURPOSE: Nocturia, a common problem in men and women, has been associated with
      chronic illnesses such as heart disease and hypertension. Using data from the
      Third National Health and Nutrition Examination Survey we investigated the
      association of nocturia with subsequent mortality risk. MATERIALS AND METHODS:
      NHANES III is a national probability survey of the United States between 1988 and
      1994. Mortality data were obtained by linkage of NHANES III to the National Death
      Index. Cox proportional hazards regression models were used to assess the
      association between nocturia and all cause mortality, controlling for potential
      confounders in a sample of 15,988 men and women 20 years old or older. RESULTS:
      The prevalence of nocturia, defined as 2 or more voiding episodes nightly, was
      15.5% in men and 20.9% in women. Multivariate analyses showed a statistically
      significant trend of increased mortality risk with increased number of voiding
      episodes in men and women. The magnitude of the nocturia and mortality
      association was greater in those younger than 65 years with attenuated
      associations in the 65 years old or older age group. CONCLUSIONS: Nocturia is a
      strong predictor of mortality, more so in younger men and women than in the
      elderly, with a dose-response pattern in increased mortality risk with increasing
      number of voiding episodes nightly. Potential underlying mechanisms of the
      observed association of nocturia and increased mortality risk include sleep
      disruption and subsequent development of related comorbid conditions.

PMID- 21168874
TI  - Oral testosterone with and without concomitant inhibition of 5alpha-reductase by
      dutasteride in hypogonadal men for 28 days.
AB  - PURPOSE: Co-administration of the 5alpha-reductase inhibitor dutasteride
      increases the oral testosterone bioavailability in men with experimentally
      induced hypogonadism. We examined oral testosterone with and without dutasteride
      administration in hypogonadal men for 28 days. MATERIALS AND METHODS: We randomly
      assigned 43 hypogonadal men to twice daily oral doses of 150, 250 or 400 mg
      testosterone with 0.25 mg dutasteride, 400 mg testosterone alone or 0.25 mg
      dutasteride alone for 28 days in a multicenter study. Subjects underwent
      pharmacokinetic profiling of serum hormones on days 1 and 28. A total of 32 men
      completed all study procedures. RESULTS: Serum testosterone increased in all
      groups on testosterone compared with that in the dutasteride only group. At the
      400 mg dose the combination of testosterone and dutasteride resulted in average
      testosterone concentrations that were 2.7 and 4.6 times higher than in the
      testosterone only group on days 1 and 28, respectively (p <0.01). On day 28
      average testosterone was 20% to 30% lower in all groups on testosterone and
      dutasteride, and 50% lower in the testosterone only group compared with day 1.
      Serum dihydrotestosterone was suppressed in all groups on dutasteride and
      increased in the testosterone only group. CONCLUSIONS: Oral testosterone
      administration resulted in a therapeutic serum testosterone concentration in
      hypogonadal men. Dutasteride improved the oral bioavailability of testosterone
      while suppressing dihydrotestosterone. Compared with day 1, testosterone was
      decreased after 28 days of administration. Additional study is warranted of oral
      testosterone with dutasteride for testosterone deficiency.

PMID- 21168876
TI  - Photoselective vaporization prostatectomy: experience with a novel 180 W 532 nm
      lithium triborate laser and fiber delivery system in living dogs.
AB  - PURPOSE: We studied vaporization parameters, and anatomical and histopathological
      outcomes of photoselective vaporization of the prostate with the novel
      GreenLightTM XPSTM 180 W, 532 nm lithium triborate laser and MoXyTM fiber in a
      survival model of living dogs. We compared these findings with those of the
      existing GreenLight HPSTM 120 W 532 nm lithium triborate laser photoselective
      vaporization of the prostate in living dogs. MATERIALS AND METHODS: Eight dogs
      underwent antegrade photoselective vaporization of the prostate with the 180 W
      laser delivered through a new 750 MUm (vs the existing 600 MUm core diameter),
      50% larger, spot sized, side firing fiber. Four dogs were sacrificed 3 hours and
      8 weeks postoperatively, respectively. We recorded laser energy and time.
      Prostates were sectioned, measured and histologically analyzed after hematoxylin
      and eosin, triphenyltetrazolium chloride or Gomori trichrome staining and
      compared with a normal control. RESULTS: Photoselective vaporization of the
      prostate with the 180 W laser bloodlessly created a 76% larger cavity (mean 11.8
      vs 6.7 cm(3), p = 0.014), vaporized tissue at a 77% higher rate (mean 2.3 vs 1.3
      cm(3) per minute, p = 0.03) and did so in 37% less time per volume vaporized (0.5
      vs 0.8 minutes per cm(3), p = 0.003). Hematoxylin and eosin, and
      triphenyltetrazolium chloride staining histologically revealed a 33% thicker mean
      coagulation zone vs that of 120 W laser photoselective vaporization of the
      prostate (2.0 +/- 0.4 vs 1.5 +/- 0.3 mm, p <0.005). In prostates healed for 8
      weeks postoperatively hematoxylin and eosin, and Gomori trichrome staining showed
      re-epithelialized cavities with negligible submucosal fibrosis compared with a
      normal prostate. CONCLUSIONS: GreenLight XPS 180 W 532 nm lithium triborate laser
      photoselective vaporization of the prostate with the MoXy fiber has a
      significantly higher vaporization rate and speed with a deeper hemostatic
      coagulation zone but favorable tissue interaction and healing equal to those of
      HPS 120 W laser photoselective vaporization of the prostate in dogs.

PMID- 21168878
TI  - Effect of n-3 fatty acid supplementation on urinary risk factors for calcium
      oxalate stone formation.
AB  - PURPOSE: Findings are inconsistent in a few studies of the effect of n-3 fatty
      acid supplementation on urinary calcium and oxalate excretion in stone formers.
      We evaluated the physiological effects of supplementation with eicosapentaenoic
      acid and docosahexaenoic acid on urinary risk factors for calcium oxalate stone
      formation under standardized conditions. MATERIALS AND METHODS: We studied 15
      healthy subjects initially while consuming a standardized diet for 5 days
      (control phase). During consecutive intervention phases 1-5-day standardized
      diet, 2-20-day free diet and 3-5-day standardized diet participants received 900
      mg eicosapentaenoic acid and 600 mg docosahexaenoic acid daily. While ingesting
      the standardized diets, daily 24-hour urine samples were collected. RESULTS:
      After short-term supplementation with eicosapentaenoic acid and docosahexaenoic
      acid in phase 1 we noted no changes in urinary parameters compared to the control
      phase. After 30-day supplementation with eicosapentaenoic acid and
      docosahexaenoic acid in phase 3 relative supersaturation with calcium oxalate
      decreased significantly by 23% from a mean +/- SD of 2.01 +/- 1.26 to 1.55 +/-
      0.84 due to significantly decreased urinary oxalate excretion (p = 0.023). Other
      urinary variables were not affected by supplementation. CONCLUSIONS: Results show
      that 30-day n-3 fatty acid supplementation effectively decreases urinary oxalate
      excretion and the risk of calcium oxalate crystallization. The mechanism of the
      physiological effect may be decreased cellular oxalic acid exchange attributable
      to an altered fatty acid pattern of membrane phospholipids with concomitant
      changes in oxalate transporter activity. Calcium oxalate stone formers may
      benefit from long-term n-3 fatty acid supplementation.

PMID- 21168877
TI  - Sarcosine in prostate cancer tissue is not a differential metabolite for prostate
      cancer aggressiveness and biochemical progression.
AB  - PURPOSE: Sarcosine in prostate cancer tissue samples was recently reported to be
      increased during prostate cancer progression to metastasis and suggested to be a
      key metabolite of cancer cell invasion and aggressiveness. We reevaluated
      sarcosine in prostate cancer tissue samples as a potential indicator of tumor
      aggressiveness, and as a predictor of recurrence-free survival. MATERIALS AND
      METHODS: Sarcosine in matched samples of malignant and nonmalignant tissue from
      92 patients with prostate cancer after radical prostatectomy was measured in the
      framework of a global metabolite profiling study of prostate cancer by gas
      chromatography/mass spectrometry. We related results to age, prostate volume,
      tumor stage, Gleason score, preoperative prostate specific antigen and
      biochemical recurrence, defined as a persistent prostate specific antigen
      increase of greater than 0.2 ng/ml. Nonparametric statistical tests, ROC curves
      and Kaplan-Meier analyses were done. RESULTS: Median sarcosine content in tissue
      was about 7% higher in matched malignant vs nonmalignant samples, which was
      significantly. Sarcosine values were not associated with tumor stage (pT2 vs
      pT3), tumor grade (Gleason score less than 7 vs 7 or greater) or biochemical
      recurrence. The lack of metastatic tissue samples was a study limitation.
      CONCLUSIONS: Sarcosine in prostate cancer tissue samples cannot be considered a
      suitable predictor of tumor aggressiveness or biochemical recurrence.

PMID- 21168879
TI  - Lichen sclerosus: epidemiological distribution in an equal access health care
      system.
AB  - PURPOSE: The incidence and demographics of lichen sclerosus range from 1/300
      (0.3%) to 1/1,000 individuals (0.1%). We analyzed the incidence of lichen
      sclerosus in an equal access health care system, hypothesizing that it is more
      common in older white males. MATERIALS AND METHODS: We reviewed the Department of
      Defense electronic medical record, Armed Forces Health Longitudinal Technology
      Application, to determine the number of unique male patients diagnosed with
      lichen sclerosus between 2003 and 2009. After removing duplicate visits we
      determined patient age and race, and the regional distribution and overall
      incidence of lichen sclerosus. RESULTS: Of the 42,648,923 unique male patients in
      the electronic medical record in this period 604 were diagnosed with lichen
      sclerosus (0.0014% or 1.4/100,000 visits). Age distribution was similar in the
      first 3 decades of life but more than doubled in the fourth through sixth decades
      with the highest prevalence at ages 61 or older (4.4/100,000 patients diagnosed
      per 100,000 visits, Pearson chi-square p <0.0001). Race distribution was Asian or
      Pacific Islander 0.9, black 1.4, other 1.7 and white 2.1 patients diagnosed per
      100,000 visits (Pearson chi-square p = 0.003). There was a trend in the regional
      distribution across the United States, as defined by the Department of Health and
      Human Services, ranging from 0.3 diagnoses per 100,000 visits in Region 2, New
      York to 2.2/100,000 in Seattle (Pearson chi-square p <0.0001). CONCLUSIONS: In
      this equal access health care system the incidence of male lichen sclerosus is
      1.4 patients per 100,000 visits. It is more common in white men after the third
      decade of life. There is an association between region and the diagnosis of
      lichen sclerosus with the highest incidence in the northwestern United States.

PMID- 21168880
TI  - Older age is associated with similar improvements in semen parameters and
      testosterone after subinguinal microsurgical varicocelectomy.
AB  - PURPOSE: It is generally accepted that men with clinically palpable varicocele
      are at high risk for a progressive decrease in fertility and testosterone levels
      with time. Varicocelectomy is thought to improve testicular function or at least
      halt the accelerated decrease in testicular function associated with varicocele.
      Substantial controversy exists as to whether varicocelectomy is effective in
      older men, possibly due to irreversible testicular damage or limited potential
      for recovery from varicocele induced damage. MATERIALS AND METHODS: We
      retrospectively reviewed the records of men who underwent microsurgical
      subinguinal varicocelectomy, as done by a single surgeon. Demographics, patient
      questionnaires, operative notes, charts, testosterone and semen analysis were
      reviewed. Patients were divided into 3 groups based on age at surgery, including
      less than 30, 30 to 39 and 40 years or greater. RESULTS: A total of 272 men met
      study inclusion criteria. In all 3 age groups we noted similar testosterone and
      baseline semen analysis parameters. There were significant increases in sperm
      concentration and total sperm count in all age groups. When analysis was
      restricted to men with baseline testosterone 400 ng/dl or less, there was a mean
      110, 133 and 136 ng/dl increase in 21 men who were 40 years old or older, in 30
      who were 30 to 39 years old and in 21 who were younger than 30 years,
      respectively. CONCLUSIONS: Microsurgical varicocelectomy resulted in significant
      increases in sperm concentration, total sperm count and testosterone in all age
      groups studied, including men in the fifth and sixth decades of life.
      Microsurgical varicocelectomy should be offered to older men for infertility
      and/or hypogonadism.

PMID- 21168881
TI  - Satisfaction and patient experience with sacral neuromodulation: results of a
      single center sample survey.
AB  - PURPOSE: We systematically assessed long-term satisfaction and patient experience
      with sacral nerve modulation therapy. MATERIALS AND METHODS: All patients who
      received sacral neuromodulation between 1990 and 2007 at our center and who still
      had the implant were included in the survey. All received a postal questionnaire
      regarding satisfaction and experiences with the system, such as side effects,
      complications, burden, impact on sexuality and defecation changes. RESULTS: Of
      the 275 questionnaires sent 207 were returned for a 75% response rate. The
      population was 83% female. Overall treatment was done for overactive bladder
      syndrome, nonobstructive urinary retention, combined overactive bladder and
      retention, and pelvic pain in 55%, 24%, 20% and 1% of patients, respectively.
      Overall satisfaction with sacral neuromodulation was high at 90%. No correlations
      were found between the satisfaction rate, and pretreatment age, gender, complaint
      type, sexual dysfunction or therapy duration. However, 56% of patients reported
      side effects, such as pain at the internal nerve stimulator site and due to
      stimulation. However, 89% of these patients did not seek further therapy. Of
      patients with additional defecation problems 47% experienced relief of
      complaints. CONCLUSIONS: This study shows a high satisfaction rate in patients
      with sacral neuromodulation. There was no relation between patient age, complaint
      type, therapy duration or side effects and the satisfaction rate. The number of
      side effects was limited but further analysis in prospective cohorts should
      identify patients who are likely to have side effects or stop sacral
      neuromodulation treatment.

PMID- 21168882
TI  - HMOX1 is an important prognostic indicator of nonmuscle invasive bladder cancer
      recurrence and progression.
AB  - PURPOSE: HMOX1, which is highly expressed in various solid tumors, has an
      important role in rapid tumor growth. We investigated the relationship between
      HMOX1 expression and clinicopathological parameters in patients with NMIBC.
      MATERIALS AND METHODS: We analyzed 211 primary NMIBC tissue specimens by real
      time PCR and compared the results with clinicopathological parameters. Kaplan
      Meier survival curves and multivariate Cox regression analysis were used to
      assess the prognostic value of HMOX1 in NMIBC cases. RESULTS: HMOX1 mRNA
      expression was significantly higher in patients with higher grade and multiple
      tumors than in those with lower grade and single tumors (each p <0.05,
      respectively). Kaplan-Meier estimates showed HMOX1 expression was significantly
      associated with recurrence and progression (log rank test p = 0.010 and <0.001,
      respectively). A multivariate Cox regression model revealed that HMOX1 mRNA
      expression was an independent predictor of recurrence (HR 1.832, p = 0.017) and
      progression (HR 5.241, p = 0.001) in patients with NMIBC. CONCLUSIONS: Analysis
      of HMOX1 expression in 211 NMIBC tissue specimens revealed its potential
      usefulness as a marker to predict the NMIBC prognosis.

PMID- 21168883
TI  - Propagation of the electrical impulse in reversible unilateral ureteral
      obstruction as determined at high electrophysiological resolution.
AB  - PURPOSE: We investigated the propagation of electrical impulses in a reversible,
      complete or partial unilateral ureteral obstruction model in vivo. MATERIALS AND
      METHODS: In Wistar rats the left mid ureter was completely (8) or partially (7)
      occluded and released after 24 hours. We recorded electrical activity of the left
      and right ureter before, during and after obstruction at different stages up to 2
      weeks after obstruction using a high resolution, 64 extracellular electrode
      probe. RESULTS: Complete obstruction in the left proximal ureter caused an
      immediate increase in frequency from a mean +/- SEM of 14.8 +/- 1.3 to 18.6 +/-
      1.7 per minute (p <0.05), followed by a 1.4 +/- 0.9 per minute decrease (p
      <0.001). Within the first 2 days after reversal velocity gradually decreased from
      1.82 +/- 0.12 to 0.79 +/- 0.17 cm per second (p <0.001). Release of obstruction
      gradually restored frequency and velocity, which returned to baseline at 2 weeks.
      Generally the alterations in rats with complete and partial obstruction were
      similar but they were less marked in those with partial obstruction. Distal to
      the obstruction site the impulses disappeared (38%) or propagated retrograde
      (43%) at some stage in the post-obstruction period. These abnormal impulse
      propagations also gradually disappeared in the post-obstruction stage.
      CONCLUSIONS: After complete or partial ureteral obstruction there were immediate,
      significant changes in the propagation of electrical impulses in the proximal and
      distal left ureter, which were generally less marked after partial than after
      complete obstruction. Reversal of obstruction resulted in the gradual
      disappearance of this abnormality in 2 weeks.

PMID- 21168884
TI  - Associated findings and complications of retroperitoneal fibrosis in 204
      patients: results of a urological registry.
AB  - PURPOSE: We studied the frequency of associated findings and complications of
      retroperitoneal fibrosis in a large clinical collective of urological patients.
      MATERIALS AND METHODS: All urology departments in Germany were invited to
      participate in a registry of patients with retroperitoneal fibrosis, for which a
      data sheet with more than 200 questions was developed. RESULTS: As of March 2010
      a total of 204 patients were registered. The male-to-female ratio was 2.1:1 and
      the average age at onset was 55.6 years. In 123 cases (60.3%) the diagnosis was
      confirmed by histopathology. Coexisting autoimmune diseases were found in 9.8% of
      patients, consisting mainly of thyroid disorders. Coexisting fibrosis was
      detected in 3.4% of the patients and 73.9% of those queried were active smokers.
      Of 176 patients for whom data on therapy were available 123 received monotherapy
      and 41 received combination therapy for a mean of 12.1 months (12 received none),
      while 87 underwent a total of 103 operative procedures. Hydronephrosis was the
      most frequent complication in 95.6% of patients. Atrophic kidney from undetected
      hydronephrosis appeared in 46 patients (22.5%) and in 4 bilateral damage
      necessitated dialysis. Complications from vascular obstruction were observed in
      27.5% of patients. Large bowel obstruction requiring colostomy occurred in 4
      patients (2.0%). CONCLUSIONS: Patients with retroperitoneal fibrosis often first
      present to urology departments upon referral for hydronephrosis. In this series
      at least 1 kidney appeared to be irreversibly damaged in more than 20% of
      patients. Urologists should be mindful of the role of smoking role as a risk
      factor, complications arising from vascular and large bowel obstructions, and the
      possible association of retroperitoneal fibrosis with autoimmune disease.

PMID- 21168885
TI  - Detection and quantitation of soluble B7-H3 in expressed prostatic secretions: a
      novel marker in patients with chronic prostatitis.
AB  - PURPOSE: We determined the soluble B7-H3 level and its clinical significance in
      serum and expressed prostatic secretions of patients with chronic prostatitis,
      including chronic bacterial prostatitis (type II) and chronic pelvic pain
      syndrome. MATERIALS AND METHODS: Using enzyme-linked immunosorbent assay we
      measured soluble B7-H3 in 11 patients with chronic prostatitis (type II), and 26
      with inflammatory (type IIIA) and 54 with noninflammatory (type IIIB) chronic
      pelvic pain syndrome, and healthy donors. We assessed differences between these
      groups using Student's t test. As determined by the National Institutes of Health
      Chronic Prostatitis Symptom Index, we correlated soluble B7-H3 with clinical pain
      using the Pearson test. RESULTS: We found no significant difference between serum
      soluble B7-H3 in healthy donors and patients with chronic prostatitis (p =
      0.897). However, soluble B7-H3 in expressed prostatic secretions was
      statistically significantly decreased in patients with chronic prostatitis vs
      controls (p <0.001). ROC using soluble B7-H3 greater than 38.82 ng/ml in
      expressed prostatic secretions distinguished patients with chronic prostatitis
      from healthy donors with 90.9% sensitivity and 83.5% specificity. Also, soluble
      B7-H3 levels in expressed prostatic secretions correlated negatively with the
      Chronic Prostatitis Symptom Index and the pain subscore. Compared to the
      pretreatment level soluble B7-H3 in expressed prostatic secretions was
      significantly increased in patients with a greater than 25% decrease in the
      Chronic Prostatitis Symptom Index total score (p = 0.016). CONCLUSIONS: Data
      indicate that the soluble B7-H3 level in expressed prostatic secretions is a
      novel chronic prostatitis marker that correlates negatively with subjective
      symptoms.

PMID- 21168886
TI  - Pencil and paper test: a new tool to predict the ability of neurological patients
      to practice clean intermittent self-catheterization.
AB  - PURPOSE: We created and validated the new pencil and paper test, which allows
      assessment of the ability of patients with a neurological disorder to practice
      clean intermittent self-catheterization. MATERIALS AND METHODS: We developed a
      simple test including common gestures mimicking the usual maneuvers needed during
      clean intermittent self-catheterization, and involving the same cognitive and
      physical resources needed for this technique. We evaluated the test in 118
      patients with a neurological condition. Instruments needed to perform the pencil
      and paper test are limited to a sheet of paper and a pencil. Each test item was
      quantified and graded with a total score of 15. A specific clean intermittent
      catheterization learning scale was used to classify the outcome of the ability to
      perform clean intermittent self-catheterization with a score range of 5--learning
      easy and self-catheterization complete to 0--learning impossible. RESULTS:
      Enrolled in the study were 118 patients with a neurological condition. There was
      strong correlation between the global pencil and paper test score, and the
      ability to perform clean intermittent self-catheterization, as evaluated by the
      learning scale (r = 0.82, p = 0.000091). At a test cutoff of 10 and a clean
      intermittent self-catheterization cutoff of 3, which was the limit needed to
      practice self-catheterization alone, the positive predictive value of the pencil
      and paper test was 85% and its negative predictive value was 94% (Cronbach's
      alpha = 0.88). CONCLUSIONS: The pencil and paper test is a valid way to predict
      the ability to practice clean intermittent self-catheterization in patients with
      a neurological disorder.

PMID- 21168887
TI  - Specific profiles of polybrominated diphenylethers (PBDEs) and polychlorinated
      biphenyls (PCBs) in fish and tucuxi dolphins from the estuary of Paraiba do Sul
      River, Southeastern Brazil.
AB  - Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are
      ubiquitous pollutants in the environment and subject of several studies due to
      their adverse effects as endocrine disruptors. Despite the concern over
      widespread distribution of PBDEs even in sparsely populated regions of the world,
      few studies have reported their occurrence in Brazil. In this study, PBDEs and
      PCBs levels were measured in selected fish species and dolphins from Paraiba do
      Sul River, Brazil. BDE 47 and 85 were the predominant congeners. Low chlorinated
      congeners showed the highest concentrations in fish; however dolphins presented
      the highest proportion of PCBs 153, followed by 138 and 180. The daily intake of
      PBDEs and PCBs was estimated for the population of this region. PCB daily intake
      through consumption of croaker was above the limits set by the Brazilian Ministry
      of Agriculture, raising great concern over the existence of a source of PCB
      contamination in Brazil.

PMID- 21168888
TI  - [Cognitive impairment: a reality in chronic fatigue syndrome].

PMID- 21168889
TI  - The transphosphatidylation potential of a membrane-bound phospholipase D from
      poppy seedlings.
AB  - Plant phospholipases D (PLDs) occur in a large variety of isoenzymes, which
      differ in Ca(2+) ion requirement, phosphatidylinositol-4,5-bisphosphate (PIP(2))
      activation and substrate selectivity. In the present study a membrane-bound PLD
      has been identified in the microsomal fractions of poppy seedlings (Papaver
      somniferum). The maximum PLD activity is found after 2 days of germination in
      endosperms and after 3 days in developing seedlings. In contrast to the four
      poppy PLD isoenzymes described hitherto, the membrane-bound form is active at
      lower Ca(2+) ion concentrations (in the micromolar instead of millimolar range)
      and needs PIP(2) for hydrolytic activity. Remarkable differences are also
      observed in head group exchange reactions. The reaction rates of the
      transphosphatidylation of phosphatidylcholine by various acceptor alcohols follow
      the sequence glycerol>serine>myo-inositol>ethanolamine, whereas ethanolamine is
      preferred by most other PLDs. Despite the biocatalytic differences, the membrane
      bound PLD interacts with polyclonal antibodies raised against alpha-type PLD,
      which reveals some structural similarities between these two enzymes.

PMID- 21168891
TI  - Burkitt's lymphoma: maximising the use of fine needle aspirates by long-term
      preservation for diagnosis and research.
AB  - Fine needle aspirates from Burkitt's lymphoma and other tumours transferred
      directly into ThinPrep(r) PreservCyt(r) (Cytyc UK Ltd, Crawley, UK) buffered
      alcohol fixative retain their cellular and viral antigens and nucleic acids for
      many months at ambient temperatures. Despite the presence of blood and debris,
      cells dried onto slides from droplets and post-fixed in formalin, or sections of
      paraffin-embedded cell blocks from formalin post-fixed pellets, prove adequate
      for morphology, immunocytochemistry, in-situ hybridization and molecular
      biological analyses. Where there is lack of expertise in making thin smears or
      hospitals lack pathology laboratories and services, PreservCyt(r) provides an
      excellent medium for transport elsewhere for diagnosis and research.

PMID- 21168892
TI  - Damping in micro-scale generalized thermoelastic circular plate resonators.
AB  - The out-of-plane vibrations of a generalized thermoelastic circular plate are
      studied under different environmental temperature, plate dimensions and boundary
      conditions. The analytical expressions for thermoelastic damping of vibration and
      phase velocity of circumferential surface wave modes are obtained. It is noticed
      that the damping of vibrations and phase velocities of circumferential surface
      wave modes significantly depend on thermal relaxation time in addition to
      thermoelastic coupling in circular plates under resonance conditions. The surface
      conditions also impose significant effects on the vibrations of such resonators.
      The expressions for displacement and temperature fields in the plate resonator
      are also derived and obtained. Some numerical results have also been presented
      for illustration purpose in case of silicon material plate.

PMID- 21168893
TI  - Reactions of tetracycline antibiotics with chlorine dioxide and free chlorine.
AB  - Tetracyclines (TCs) are a group of widely used antibiotics that have been
      frequently found in the aquatic environment. The potential reactions of TCs with
      common water disinfection oxidants such as chlorine dioxide (ClO(2)) and free
      available chlorine (FAC) have not been studied in depth and are the focus of this
      study. The oxidation kinetics of tetracycline, oxytetracycline,
      chlorotetracycline and iso-chlorotetracycline by ClO(2) and FAC are very rapid
      (with large apparent second-order rate constants k(app) = 2.24 * 10(5)-1.26 *
      10(6) M(-1) s(-1) with ClO(2) and k(app) = 1.12 * 10(4)-1.78 * 10(6) M(-1) s(-1)
      with FAC at pH 7.0) and highly dependent on pH. Species-specific rate constants
      are obtained by kinetic modeling that incorporates pH-speciation of TCs and the
      oxidants (for FAC), and reveal that TCs primarily react with ClO(2) and FAC by
      their unprotonated dimethylamino group and deprotonated phenolic-diketone group.
      The modest difference in reactivity among the four TCs toward the oxidants is
      consistent with expectation and can be explained by structural influences on the
      two reactive moieties. Product evaluation shows that oxidation of TCs by ClO(2)
      leads to (hydr)oxylation and breakage of TC molecules, while oxidation of TCs by
      FAC leads to chlorinated and (hydr)oxylated products without any substantial ring
      breakage. Results of this study indicate that rapid transformation of TCs by
      oxidants such as ClO(2) and FAC under water and wastewater treatment conditions
      can be expected.

PMID- 21168894
TI  - Microdistribution patterns of macroinvertebrate communities upstream and
      downstream of organic effluents.
AB  - The present study analyses the distribution patterns of macroinvertebrate
      communities in four microhabitats (riffles, glides, leaf litter and bank roots)
      upstream and downstream of two waste water treatment plant (WWTP) effluents in
      northern Spain rivers. Macroinvertebrate communities were analysed in November
      2006 by taking 5 samples from each of the microhabitats under unaffected
      (upstream WWTP) and affected (downstream WWTP) conditions, respectively. Water
      velocity, depth, substrate coarseness and hydraulic stress by means of the Froude
      number were also estimated at all sampling locations. Under unaffected
      conditions, the abundance and presence/absence of certain macroinvertebrate taxa
      were mainly determined by hydraulic characteristics (water velocity and Froude
      number) and feeding resource availability. However, neither macroinvertebrate
      richness nor abundance were neither significantly correlated with hydraulic
      stress nor substrate coarseness, although the number of macroinvertebrate taxa
      increased in microhabitats with high structural complexity. Macroinvertebrate
      abundance increased downstream of both WWTPs, while macroinvertebrate richness
      was not adversely affected by the organic enrichment of water. The structure and
      composition of macroinvertebrate communities occurring in riffles was similar
      under unaffected and affected conditions, while communities from leaf litter and
      submerged bank roots showed important changes above and below the WWTPs,
      indicating that they are probably the most appropriate communities for water
      quality assessment.

PMID- 21168895
TI  - In vitro biological effects of airborne PM2.5 and PM10 from a semi-desert city on
      the Mexico-US border.
AB  - Compelling evidence indicates that exposure to urban airborne particulate matter
      (PM) affects health. However, how PM components interact with PM-size to cause
      adverse health effects needs elucidation, especially when considering soil and
      anthropogenic sources. We studied PM from Mexicali, Mexico, where soil particles
      contribute importantly to air pollution, expecting to differentiate in vitro
      effects related to PM-size and composition. PM samples with mean aerodynamic
      diameters <=2.5MUm (PM(2.5)) and <=10MUm (PM(10)) were collected in Mexicali
      (October 2005-March 2006) from a semi-urban (expected larger participation of
      soil sources) and an urban (predominately combustion sources) site. Samples were
      pooled by site and size, analyzed for elemental composition (particle-induced X
      ray emission) and tested in vitro for: induction of human erythrocytes membrane
      disruption (hemolysis) (colorimetrically); inhibition of cell proliferation (ICP)
      (crystal violet) and TNFalpha/IL-6 secretion (ELISA) using J774.A1 murine
      monocytic cells; and DNA degradation using Balb/c3T3 cell naked DNA
      (electrophoretically). Results of PM elemental composition principal component
      analysis were used in associating cellular effects. Sixteen elements identified
      in PM grouped in two principal components: Component(1) (C(1)): Mg, Al, Si, P,
      Cl, K, Ca, Ti, V, Cr, Fe, and Component(2) (C(2)): Cu, Zn. Hemolysis was
      predominately induced by semi-urban-PM(10) (p<0.05) and was associated with urban
      PM(10)C(1) (r=0.62, p=0.003). Major ICP resulted with semi-urban PM(2.5)
      (p<0.05). TNFalpha was mainly induced by urban samples regardless of size
      (p<0.05) and associated with urban-PM(2.5)C(2) (r=0.48, p=0.02). Both PM(10)
      samples induced highest DNA degradation (p<0.05), regardless of location. We
      conclude that PM-size and PM-related soil or anthropogenic elements trigger
      specific biological-response patterns.

PMID- 21168896
TI  - Arsenic and mercury bioaccumulation in the aquatic plant, Vallisneria
      neotropicalis.
AB  - Arsenic (As) and mercury (Hg) are among the most toxic metals/metalloids. The
      overall goal of this study was to investigate the bioaccumulation of these trace
      elements in Vallisneria neotropicalis, a key trophic species in aquatic
      environments. For this purpose, As and Hg concentrations were determined in
      sediments and natural populations of V. neotropicalis in sub-estuaries of Mobile
      Bay (Alabama, USA), differing with respect to past and present anthropogenic
      impact. Analyses indicate that the Fish River is the most contaminated among the
      sub-estuaries investigated; levels of As found in Fish River sediments fall
      within a range that could potentially cause adverse effects in biota. Sediment As
      concentrations were only moderately correlated with those in V. neotropicalis; no
      correlation was found between sediment and plant Hg levels. However, several
      parameters could have masked such potential relationships (e.g., differences in
      sediment characteristics and "biological dilution" phenomena). Results presented
      herein highlight the numerous parameters that can influence metal/metalloids
      accumulation in aquatic plants as well as species-specific responses to trace
      element contamination. Finally, this study underscores the need for further
      investigation into contaminant bioaccumulation in ecologically and economically
      important coastal environments.

PMID- 21168897
TI  - Oxidative stress, endothelial dysfunction and inflammatory response in rat heart
      to NO2 inhalation exposure.
AB  - Epidemiological studies suggest that NO2 inhalation is associated with adverse
      effects on heart-related health, however, existing experimental data lack
      relevant evidences. In this study, a role for oxidative stress, endothelial
      dysfunction and inflammatory responses in the heart of rats treated with
      different concentrations of NO2 (0, 5, 10 and 20 mg m-3) was investigated. Mild
      heart pathology occurred after 7-d exposure (6 h d-1). Marked oxidative stress
      were induced as evaluated by reduction/induction of antioxidants (Cu/Zn-SOD, Mn
      SOD and GPx) activity and increasing formation of MDA and PCO. Also, mRNA and
      protein biomarkers of vasoconstriction (ET-1, eNOS) and inflammation (TNF-alpha,
      IL-1beta and ICAM-1) were up-regulated, and p53 mRNA expression, bax/bcl-2 ratio
      and the mean number of TUNEL-positive myocytes were increased as well. All the
      results implicate that NO2 exerted injuries to mammals' heart, and the damage
      mechanisms were possibly associated with oxidative stress, endothelial
      dysfunction and inflammation.

PMID- 21168898
TI  - Natural, anthropogenic and fossil organic matter in river sediments and suspended
      particulate matter: a multi-molecular marker approach.
AB  - Different classes of organic matter (OM) have been systematically investigated in
      sediments and suspended particulate matter (SPM) along the Danube River in order
      to understand causes of compositional changes. Analytical pyrolysis revealed the
      dominance of natural organic matter (NOM) in most of the samples. The
      predominance of aquatic biomass is evident mainly from the abundance of
      organonitrogen compounds and phenol distributions. As the river enters a forested
      gorge, the terrestrial component of the NOM in sediments is more significant.
      This is reflected in abundant methoxyphenols and a very high carbon preference
      index. SPM sample from a tributary shows a unique geochemical signature. It
      contains abundant carboxylic acids, amines, isoprenoids in the pyrolyzate, and is
      dominated by phytol and 24-methyl-cholesta-5,24(28)-dien-3beta-ol in the extract,
      produced by a diatom bloom. Wax esters with a relatively high proportion of
      short, methyl-branched alkyl-chains appear together with abundant phytadienes and
      n-C(17) alkane in some samples, suggesting a microbial origin. Anthropogenic OM
      from runoff and atmospheric deposition was evident from a minor input of
      polycyclic aromatic hydrocarbons (PAHs) originating from mixed combustion
      sources. Multivariate analysis using PAH data led us to define simple molecular
      ratios to distinguish the PAH composition in sand and silty sediments. The newly
      defined ratios are the alkylated phenanthrenes and anthracenes ratio (APA; C(1)
      C(3)/C(0)-C(3) phenanthrenes and anthracenes) and the PAH ring number ratio (RN;
      5-6 ring parent PAHs/all parent PAHs). This demonstrates that alkylated, as well
      as 5-6 ring PAHs are better preserved in the finer than in coarser grained
      sediments. A ubiquitous, but minor input of petroleum-related contamination with
      a uniform composition was evident in all samples as revealed by the analysis of
      petroleum biomarkers. This study demonstrates that the investigation of different
      classes of riverine OM requires a detailed molecular analysis, applying a series
      of analytical techniques and adequate statistical data treatment.

PMID- 21168899
TI  - In situ measurements of SO2, NOx, NOy, and O3 in Beijing, China during August
      2008.
AB  - The measurement of SO(2), O(3), NO, NO(2), and NO(y) mixing ratios was conducted
      from Jul 28, 2008 to Sep 2, 2008 at the Institute of Atmospheric Physics, Chinese
      Academy of Sciences (IAP, CAS) station, which is 2km southwest to the Beijing
      National Stadium (Bird's Nest/Olympic Stadium). Photochemical pollution was
      detected during the measurement on Aug 2, 2008, and the maximum hourly average
      [O(3)] reached 128ppbv, caused by both the local photochemical reactions and
      regional transportation of pollutants. The NO(x) Ozone Production Efficiency (OPE
      (NO(x))) values were 6.9 and 20.2 on Aug 2 and Aug 24, 2008 respectively, which
      were the two days with highest O(3) pollution. The OPE (NO(x)) of 6.9 on Aug 2
      was within a typical range in city area, and it implied that the high O(3) could
      be due to local sources. While OPE (NO(x)) of 20.2 on Aug 24 was larger than the
      typical value in the region, but lower than that of the surrounding clean area
      during 2008 Beijing Olympics Closing Ceremony. It indicated that the pollution
      was because of regional transportation of pollutants. In addition, 60% of the
      extent of the Smog Production Model (SPM) data was less than 0.6 and the rest was
      slightly larger than 0.6, with maximum of 0.78. It indicated that the sensitivity
      of O(3) generated was volatile organic compounds (VOCs) control during the
      observation period. The SPM results also implied that O(3) product in high-O(3)
      day is a transition state from VOCs sensitivity to NO(x) sensitivity. Lastly, the
      analysis of the wind direction and extent of SPM showed that the photochemical
      pollution of this region was mostly subject to the influence of southeastern air
      flow in the summer.

PMID- 21168900
TI  - Immunolocalization of glycodelin in human adenocarcinoma of the lung, squamous
      cell carcinoma of the lung and lung metastases of colonic adenocarcinoma.
AB  - Glycodelin (Gd), which is localized in cells of bronchial epithelium, type II
      pneumocytes and alveolar macrophages in rats and humans, plays an important role
      in the pulmonary immune response in asthmatic inflammation. In this study,
      sections of paraffin-embedded tumor adjacent lung tissue and sections of
      adenocarcinoma of the lung, squamous cell carcinoma of the lung and metastases of
      colonic adenocarcinoma were investigated for the distribution and expression of
      Gd using a polyclonal anti-Gd antibody. Glycodelin protein is located in the
      cytoplasm of bronchial epithelial cells, pneumocytes and alveolar macrophages.
      Furthermore, Gd is expressed in adenocarcinoma and squamous cell carcinoma of the
      lung as well as in lung metastases of colonic adenocarcinoma. Densitometric
      analyses showed a significantly increased expression of glycodelin protein in
      cancer tissue compared to tumor adjacent lung tissue. The Gd protein level was
      1.7-2.6-fold increased in lung carcinoma compared to tumor adjacent lung tissue.
      The Gd protein level did not differ from each other between the investigated
      types of cancer tissue. Because these data validate the recent findings of Gd
      mRNA expression, it may be concluded that glycodelin plays an important role in
      the pathogenesis of lung cancer and lung metastases.

PMID- 21168901
TI  - Intravesical electromotive botulinum toxin type A administration: part I-
      Experimental study.
AB  - OBJECTIVES: To evaluate the depth and pattern of botulinum toxin type A (BTX-A)
      distribution throughout the rabbit bladder wall by intravesical electromotive
      drug administration (EMDA). METHODS: In an experimental study, 15 male healthy
      New Zealand white rabbits were allocated in 3 groups of BTX-A injection into the
      bladder wall, intravesical electromotive BTX-A administration (BTX-A/EMDA), and
      electromotive saline administration. In BTX-A injection group, a total dose of 10
      IU/kg of BTX-A (Dysport) was injected into 10 sites of bladder detrusor muscle
      using a 6-Fr rigid cystoscope. In BTX-A/EMDA group, a current generator delivered
      a total of 2-2.4 mA with a frequency of 2.5 kHz to a fully distended bladder
      containing 10 IU/kg BTX-A for 15 minutes. In electromotive saline administration
      group, electrical current with the same characteristics was delivered to a saline
      filled bladder. Three different specimens from the bladder dome, posterior, and
      anterior bladder walls were obtained and submitted for pathologic evaluation.
      RESULTS: Pattern of immunohistochemical staining in bladder specimens from BTX-A
      injection group was weak and heterogeneous in the urothelium, interstitium, and
      muscular layers. However, in BTX-A/EMDA group the staining was uniform in
      urothelium, interstitial and muscular layers in all submitted specimens. In
      electromotive saline administration group, the urothelium, interstitium, and
      muscular layers were intact. CONCLUSIONS: There is no clinical or experimental
      report of intravesical BTX-A/EMDA in the literature. This method demonstrated
      deep and homogenous penetration of the toxin throughout the urinary bladder
      layers compared with the intravesical BTX-A injection.

PMID- 21168902
TI  - Understanding prostate cancer spending growth among Medicare beneficiaries.
AB  - OBJECTIVE: To understand whether growth in prostate cancer spending is a result
      of selected use of expensive services or greater overall usage. Growth in
      prostate cancer spending continues to outpace that for overall health
      expenditures, garnering nearly $7 billion annually. METHODS: We identified
      patients diagnosed with prostate cancer between January 1, 1992 and December 31,
      2003 using Surveillance, Epidemiology, and End Results-Medicare data. Patients
      were sorted into 12 cohorts based on their diagnosis year. We price-adjusted and
      tallied all prostate cancer-related Medicare payments for the first 2 years after
      diagnosis. We characterized the impact of a service by quantifying its
      contribution to the variation of per capita spending over time. We further
      assessed whether leading services contributed to spending growth by price or
      usage. RESULTS: Per capita Medicare expenditures increased by 20% from $8933 to
      $10,734. Decreases in inpatient expenditures ($3499 to $1504, P value for trend
      <.001) were offset by growth in physician spending ($3317-$6062, P value for
      trend <.001). Androgen deprivation (41.6%) and radiation therapy (19.9%)
      accounted for the majority of spending growth through increases in quantity.
      Depending on the service, quantity, as opposed to price, was responsible for
      59.0% to 76.4% of the observed spending growth. CONCLUSIONS: Medicare spending
      for prostate cancer care increased by 20% and was fueled by increasing usage of
      physician services, including androgen deprivation and radiation therapy. Payment
      reform and bolstering the evidence base can potentially improve the efficiency of
      prostate cancer care.

PMID- 21168903
TI  - Effectiveness of primary endoscopic incision in treatment of ectopic ureterocele
      associated with duplex system.
AB  - OBJECTIVES: To report our experience with the endoscopic treatment of ectopic
      ureterocele to demonstrate its long-term effectiveness. Endoscopic treatment is
      often recommended as the initial and definitive treatment in patients with
      ureterocele. METHODS: A total of 46 children with ectopic ureterocele in a duplex
      system underwent primary endoscopic incision from January 1998 to January 2006.
      The mean follow-up was 3.8 years. Of the 46 children, 35 had been diagnosed
      prenatally and 11 had been diagnosed after birth because of a urinary tract
      infection. Low-dose antibiotic prophylaxis was administered to all children and
      was maintained until voiding cystourethrography showed no reflux. The pre- and
      postoperative evaluation included clinical assessment, ultrasound evaluation,
      diethylenetriaminepentacetic acid renography, and cyclic voiding
      cystourethrography. RESULTS: Ureterocele decompression was achieved in 43
      patients (93%). Three patients required additional surgery for persistent
      ureterocele (1 underwent ureteroureterostomy and 2 ureteropyelostomy). None of
      our patients showed deterioration of renal function after the procedures.
      Vesicoureteral reflux was seen in the lower moiety of the ipsilateral kidney in
      14 patients (30%). Of the 14 patients with vesicoureteral reflux, 10 had
      spontaneous resolution. The remaining 4 underwent endoscopic correction. Five
      patients (10%) developed de novo vesicoureteral reflux in the ipsilateral
      ureterocele moiety. Of these 5 patients, 3 were treated with endoscopic injection
      and 2 had spontaneous resolution after 6 months of follow-up. CONCLUSIONS: Our
      data have shown that primary endoscopic puncture of a ureterocele is a simple,
      long-term, effective, and safe procedure, avoiding complete reconstruction in
      most patients.

PMID- 21168904
TI  - Twelve-year experience with laparoscopic radical hysterectomy and pelvic
      lymphadenectomy in cervical cancer.
AB  - OBJECTIVES: This study aims to evaluate the morbidity, oncological outcome, and
      prognostic factors of cervical cancer patients treated with laparoscopic radical
      hysterectomy and pelvic lymphadenectomy (LRH). METHODS: Patients with cervical
      cancer undergoing LRH at the First People's Hospital of Foshan between August
      1998 and March 2010 were enrolled in this study. The medical records were
      reviewed. RESULTS: A total of 240 patients were identified. According to FIGO
      stage, the number of patients with stage Ia2, Ib1, Ib2, IIa, and IIb was 2, 163,
      34, 35, and 6, respectively. The conversion rate was 1.25%. Intraoperative and
      postoperative complications occurred in 7.08% and 9.16% patients, respectively.
      Other medical problems included 74 cases (30%) of bladder dysfunction. Excluding
      the lost cases, the median follow-up of 221 cases was 35 months, and 5-year
      survival rate for Ia2, Ib1, Ib2, IIa was 100%, 82%, 66%, 60%, respectively.
      Univariate analysis showed factors impacting the survival rate were FIGO
      stage>Ib1, non-squamous histologic type, deep cervical stromal invasion, and
      lymph node metastasis (P=0.027, 0.023, 0.007, 0.000). The Cox-proportional
      hazards regression analysis indicated that only lymph node metastasis (OR=3.827,
      P=0.000) was independent of poor prognostic factor. The 5-year survival rates in
      Ib1 were 88% with negative lymph nodes and 59% with positive lymph nodes
      (P=0.000). CONCLUSIONS: Our data demonstrate that LRH can be performed in stage
      Ia2-Ib1 or less advanced node negative cervical cancer patients without
      compromising survival. The feasibility of LRH for more advanced patients needs
      further investigations.

PMID- 21168905
TI  - Novel nanotechnology approaches to diagnosis and therapy of ovarian cancer.
AB  - OBJECTIVE: Ovarian carcinoma is the leading cause of death from gynecologic
      malignancies, which is a direct outcome of missing its diagnosis at an early
      stage. Approximately 75% of ovarian cancer patients are initially diagnosed with
      disseminated intra-abdominal disease (stages III-IV) when ~30% of patients have a
      5-year survival rate. In addition to the challenge of early detection of ovarian
      cancer, its therapy presents several challenges including the route of therapy,
      resistance to therapy with recurrence of cancer, and specific targeting of
      ovarian cancer to reduce cytotoxic side effects. METHODS: We reviewed recent
      literature employing nanotechnology approaches to diagnosis and therapy of
      ovarian cancer. RESULTS: Recent innovations in nanotechnology with applications
      in cancer diagnostics and therapy help circumvent many pre-existing problems with
      conventional chemotherapy and present new ways of diagnosis and therapy.
      CONCLUSIONS: Nanotechnology has promising potential in enhancing early detection
      of ovarian cancer and treatment of recurrent disease.

PMID- 21168906
TI  - Hodgkin lymphoma in 2 children with chronic granulomatous disease.

PMID- 21168908
TI  - "He cheated on me, I cheated on him back": Mexican American and White
      adolescents' perceptions of cheating in romantic relationships.
AB  - A qualitative approach was used to explore the meaning and perceptions of
      cheating in adolescent romantic relationships. Mexican American and White
      adolescents (N = 75; 53.3% girls; 56.1% Mexican American), separated by gender
      and ethnicity into 12 focus groups (three groups per type), discussed personal
      and peer experiences of cheating in dating relationships as both the victim and
      perpetrator. Dialogue was coded using inductive content analysis; two broader
      cheating themes encompassing six sub-themes emerged 1) perceptions of cheating
      (individual-oriented, peer-oriented, and frequency of occurrence) and 2)
      consequences of cheating (commitment, emotional responses, and relationship
      outcomes). Mexican American girls spoke most frequently and strongly about
      cheating, followed by White girls. The meaning and contexts of cheating by
      ethnicity and gender has important implications for promoting healthy dating
      behavior during adolescence.

PMID- 21168907
TI  - Monomer elution from nanohybrid and ormocer-based composites cured with different
      light sources.
AB  - OBJECTIVES: To study monomer elution from four resin-based composites (RBCs)
      cured with different light sources. METHODS: Twenty-eight premolars were randomly
      allocated to four groups. Standardized cavities were prepared and restored with a
      nanohybrid (Filtek Supreme XT or Tetric EvoCeram), an ormocer (Admira) or a
      microhybrid RBC (Filtek Z250) which served as control. Buccal restorations were
      cured with a halogen and oral restorations with an LED light-curing unit. Elution
      of diurethane dimethacrylate (UDMA), Bisphenol A diglycidylether methacrylate
      (BisGMA), triethylene glycol dimethacrylate (TEGDMA) and 2-hydroxyethyl
      methacrylate (HEMA) was analyzed using high-performance liquid chromatography
      (HPLC) 1h to 28 days post-immersion in 75% ethanol. Data were analyzed using
      multivariate and repeated measures analysis of variance (alpha = 0.05). RESULTS:
      The greatest elution of UDMA and BisGMA occurred from Tetric EvoCeram and the
      least from Filtek Z250 (p < 0.05). LED and halogen light-curing units gave
      similar results for all RBCs (p > 0.05) except Tetric EvoCeram which showed
      greater elution for the LED unit (p < 0.05). TEGDMA was below the limit of
      quantification. HEMA eluted in similar concentrations from Filtek Supreme and
      Tetric EvoCeram (p > 0.05). SIGNIFICANCE: The two nanohybrid RBCs eluted more
      cross-linking monomers than the ormocer and the control microhybrid RBC.
      Continuous elution over 28 days indicates that RBCs act as a chronic source of
      monomers in clinical conditions. Light source may affect monomer elution since
      differences were found for one out of four RBCs. Mathematical models for elution
      kinetics of UDMA and BisGMA indicated two elution mechanisms.

PMID- 21168909
TI  - European conference on chronic respiratory disease.

PMID- 21168910
TI  - The maintenance of pluripotency following laser direct-write of mouse embryonic
      stem cells.
AB  - The ability to precisely pattern embryonic stem (ES) cells in vitro into
      predefined arrays/geometries may allow for the recreation of a stem cell niche
      for better understanding of how cellular microenvironmental factors govern stem
      cell maintenance and differentiation. In this study, a new gelatin-based laser
      direct-write (LDW) technique was utilized to deposit mouse ES cells into defined
      arrays of spots, while maintaining stem cell pluripotency. Results obtained from
      these studies showed that ES cells were successfully printed into specific
      patterns and remained viable. Furthermore, ES cells retained the expression of
      Oct4 in nuclei after LDW, indicating that the laser energy did not affect their
      maintenance of an undifferentiated state. The differentiation potential of mouse
      ES cells after LDW was confirmed by their ability to form embryoid bodies (EBs)
      and to spontaneously become cell lineages representing all three germ layers,
      revealed by the expression of marker proteins of nestin (ectoderm), Myf-5
      (mesoderm) and PDX-1 (endoderm), after 7 days of cultivation. Gelatin-based LDW
      provides a new avenue for stem cell patterning, with precision and control of the
      cellular microenvironment.

PMID- 21168911
TI  - Synthetic cationic amphiphilic alpha-helical peptides as antimicrobial agents.
AB  - Antimicrobial peptides (AMPs) secreted by the innate immune system are prevalent
      as the effective first-line of defense to overcome recurring microbial invasions.
      They have been widely accepted as the blueprints for the development of new
      antimicrobial agents for the treatment of drug resistant infections. However,
      there is also a growing concern that AMPs with a sequence that is too close to
      the host organism's AMP may inevitably compromise its own natural defense. In
      this study, we design a series of synthetic (non-natural) short alpha-helical
      AMPs to expand the arsenal of the AMP families and to gain further insights on
      their antimicrobial activities. These cationic and amphiphilic peptides have a
      general sequence of (XXYY)(n) (X: hydrophobic residue, Y: cationic residue, and
      n: the number of repeat units), and are designed to mimic the folding behavior of
      the naturally-occurring alpha-helical AMPs. The synthetic alpha-helical AMPs with
      3 repeat units, (FFRR)(3), (LLRR)(3), and (LLKK)(3), are found to be more
      selective towards microbial cells than rat red blood cells, with minimum
      inhibitory concentration (MIC) values that are more than 10 times lower than
      their 50% hemolytic concentrations (HC(50)). They are effective against Gram
      positive B. subtilis and yeast C. albicans; and the studies using scanning
      electron microscopy (SEM) have elucidated that these peptides possess membrane
      lytic activities against microbial cells. Furthermore, non-specific immune
      stimulation assays of a typical peptide shows negligible IFN-alpha, IFN-gamma,
      and TNF-alpha inductions in human peripheral blood mononuclear cells, which
      implies additional safety aspects of the peptide for both systemic and topical
      use. Therefore, the peptides designed in this study can be promising
      antimicrobial agents against the frequently-encountered Gram-positive bacteria-
      or yeast-induced infections.

PMID- 21168912
TI  - The localization of brain sites of anxiogenic-like effects of urocortin-2.
AB  - The influence of intracerebroventricullary-administered urocortin-2, a selective
      corticotropin-releasing factor receptor 2 (CRF(2)) agonist, on rat anxiety-like
      behaviour, the expression of c-Fos and CRF, and plasma corticosterone levels was
      examined in the present study. When applied to animals exposed to the conditioned
      fear-induced context, urocortin-2 enhanced a conditioned freezing fear response.
      Urocortin-2 also significantly decreased rat exploratory activity in the open
      field test. Exogenous urocortin-2 increased the conditioned fear-induced
      expression of c-Fos in the central amygdala (CeA), and parvocellular neurons of
      the paraventricular hypothalamic nucleus (pPVN), and revealed the effect of
      conditioned fear in the medial amygdala (MeA). In the fear-conditioned animals,
      immunocytochemistry showed an increase in the density of CRF-related
      immunoreactive complexes in the lateral septum (LS), 35min after urocortin-2
      administration and 10min after the conditioned fear test, compared with saline
      pretreated fear-conditioned animals. These data suggest a role of urocortin-2 in
      the behavioural and immunocytochemical responses to stress, in which it
      strengthens the measures of anxiety-like responses.

PMID- 21168913
TI  - Antibody-targeted horseradish peroxidase associated with indole-3-acetic acid
      induces apoptosis in vitro in hematological malignancies.
AB  - Indole-3-acetic acid (IAA), when oxidized by horseradish peroxidase (HRP), is
      transformed into cytotoxic molecules capable of inducing cell injury. The aim of
      this study was to test if, by targeting hematopoietic tumors with HRP-conjugated
      antibodies in association with IAA treatment, there is induction of apoptosis. We
      used two lineages of hematologic tumors: NB4, derived from acute promyelocytic
      leukemia (APL) and Granta-519 from mantle cell lymphoma (MCL). We also tested
      cells from 12 patients with acute myeloid leukemia (AML) and from 10 patients
      with chronic lymphocytic leukemia (CLL). HRP targeting was performed with anti
      CD33 or anti-CD19 antibodies (depending on the origin of the cell), followed by
      incubation with goat anti-mouse antibody conjugated with HRP. Eight experimental
      groups were analyzed: control, HRP targeted, HRP targeted and incubated with 1, 5
      and 10mM IAA, and cells not HRP targeted but incubated with 1, 5 and 10mM IAA.
      Apoptosis was analyzed by flow cytometry using annexin V-FITC and propidium
      iodide labeling. Results showed that apoptosis was dependent on the dose of IAA
      utilized, the duration of exposure to the prodrug and the origin of the
      neoplasia. Targeting HRP with antibodies was efficient in activating IAA and
      inducing apoptosis.

PMID- 21168914
TI  - Study of the correlation between psychiatric and psychological diagnoses in
      sample offenders.
AB  - This study deals with the frequency with which expert psychiatrists and
      psychologists make structural or nosographic diagnoses within the context of
      expert assessment. Thus, the rates of concordance between psychiatrists and
      psychologists in both types of diagnoses will be assessed. To do so, the level of
      inter-observer agreement on diagnoses between 1990 and 2003 was studied
      retrospectively in France through psychiatric and psychological assessments of
      505 male offenders. The assessment of the correlation rates was carried out using
      the Kappa coefficient. The results show a range of 0.55 to 0.71 in inter-observer
      (psychiatrists vs psychologists) agreement for structural diagnoses, and 0.51 to
      0.89 for nosographic diagnoses. In addition, a marked correlation between
      psychiatrists and psychologists may be noted regarding abstention in both
      structural (k=66) and nosographic (k=73) diagnoses. In fact, recommendations are
      made for improvement in the consistency of offender assessment in the psycho
      legal French context.

PMID- 21168915
TI  - Accelerated acute allograft rejection accompanied by enhanced T-cell
      proliferation and attenuated Treg function in RBP-J deficient mice.
AB  - Acute allograft rejection (AAR) involves both the innate and the adaptive immune
      systems. As a critical pathway in peripheral T-cell differentiation and function,
      Notch signaling is potentially involved in the modulation of AAR, but its role in
      alloimmune responses has not been fully addressed. By using fully MHC-mismatched
      allograft transplantation model and T-cell specific RBP-J deficient mice, we
      examined the role of Notch/RBP-J pathway in alloimmune responses in vivo. AAR was
      significantly accelerated in RBP-J deficient mice compared with the wild-type
      controls, as demonstrated by the marked reduction in graft survival. The
      reduction in graft survival was associated with augmented alloantigen specific T
      cell proliferation and increased number of Th1, Th2, and Th17 cells in the RBP-J
      deficient recipient mice. Furthermore, although the frequency of
      CD4(+)CD25(+)Foxp3(+) Tregs was intact in RBP-J knockout recipients, their
      ability to suppress Teff responses in vitro was significantly dampened. These
      findings suggest that Notch/RBP-J pathway may attenuate AAR by suppressing in
      vivo expansion of alloreactive T-cell proliferation and facilitating
      CD4(+)CD25(+) Treg suppression ability, indicating that Notch pathway could be
      exploited to limit T-cell-mediated AAR.

PMID- 21168917
TI  - Aggression, ADHD symptoms, and dysphoria in children and adolescents diagnosed
      with bipolar disorder and ADHD.
AB  - BACKGROUND: This study had two objectives: (1) examine characteristics of
      aggression in children and adolescents diagnosed with bipolar disorder and (2)
      determine whether the CBCL pediatric bipolar disorder profile differentiated
      youngsters with bipolar disorder from youngsters with ADHD. METHOD: Children and
      adolescents referred to a pediatric psychopharmacology clinic were systematically
      evaluated for psychopathology using a psychiatrist-administered diagnostic
      interview, parent- and teacher-report rating scales assessing the child's
      behavior, and child-completed self-report scales. In this sample, 27 children and
      adolescents were diagnosed with bipolar disorder and 249 youngsters were
      diagnosed with ADHD without co-occurring bipolar disorder. These two groups were
      compared to determine whether there were significant differences on various
      measures of psychopathology. RESULTS: Youngsters diagnosed with bipolar disorder
      were more verbally aggressive and exhibited higher levels of reactive aggression
      than youngsters with ADHD without co-occurring bipolar disorder. Youngsters with
      bipolar disorder also reported higher levels of depressive symptoms than
      youngsters with ADHD without bipolar disorder. The CBCL pediatric bipolar
      disorder profile did not accurately identify youngsters diagnosed with bipolar
      disorder. CONCLUSIONS: The present findings present a picture of manic youngsters
      as verbally aggressive and argumentative, who respond with anger when frustrated.
      Youngsters diagnosed with bipolar disorder and ADHD exhibited significant levels
      of impulsive behavior and attention problems, but youngsters with bipolar
      disorder also exhibited significant levels of aggressive behavior and dysphoric
      mood. Finally, the CBCL pediatric bipolar disorder profile did not accurately
      identify youngsters who were diagnosed with bipolar disorder.

PMID- 21168918
TI  - Chronic conditions and major depression in community-dwelling older adults.
AB  - OBJECTIVES: To estimate (1) the prevalence of long-term medical conditions and of
      comorbid major depression, and (2) the associations between major depression and
      various chronic medical conditions in a general population of older adults (over
      50 years of age) and in persons who are traditionally classified as seniors (65
      years and older). METHODS: Data from the Canadian Community Health Survey- Mental
      Health and Wellbeing (CCHS-1.2) were analyzed. Non-institutionalized individuals
      over 15 years of age in the 10 Canadian provinces were sampled in the CCHS-1.2.
      The entire sample of the CCHS-1.2 consisted of 36,894 individuals, for the main
      analyses in this study the dataset was restricted to those aged 50 and over
      (n=15,591). Chronic health conditions were assessed using a self-report method of
      doctor diagnosis. The World Mental Health-Composite Diagnostic Interview was used
      to asses major depressive episodes based on DSM-IV criteria. RESULTS: The overall
      prevalence of having at least one chronic condition in those over 50 years of age
      was 82.4%, compared to 62.0% in those under 50. The prevalence of a major
      depressive episode in those over 50 with one chronic condition was 3.7%, compared
      with 1.0% in those without a long-term medical condition. The top 3 chronic
      health conditions in seniors aged 65 or older were arthritis/rheumatism, high
      blood pressure and back problems. Chronic Fatigue Syndrome, fibromyalgia and
      migraine headache had the highest comorbidity with major depression in the senior
      population. LIMITATIONS: The use of self-report data on chronic health
      conditions, potential diagnostic overlap between conditions, and the inability to
      make causal inferences due to the cross-sectional nature of the data are all
      limitations of the current study. CONCLUSIONS: Differences were found between
      rates of chronic conditions and major depression between the general population,
      older adults and seniors in this study. Further research is needed to delineate
      the direction of these relationships in seniors. Primary and secondary prevention
      efforts should target seniors who exhibit symptoms of depression or highly
      prevalent chronic health conditions.

PMID- 21168916
TI  - Differences in suicide risk according to living arrangements in Japanese men and
      women--the Japan Public Health Center-based (JPHC) prospective study.
AB  - BACKGROUND: Living alone has been suggested as a risk factor for suicide.
      However, the effect on suicide risk of living together with spouse, child(ren)
      and parent(s) is unclear. This study aims to examine the association between
      living arrangements with spouse, child(ren), and parent(s) and suicide in a
      Japanese men and women. METHODS: Altogether 104, 528 participants aged 40-69
      years, who completed baseline questionnaire (1990-1994), were followed for death
      through December 2005. We used Cox proportional hazards regression model to
      estimate the hazard ratio (HR) and 95% confidence intervals (95% CI) for suicide
      according to living arrangements. RESULTS: During an average 13.2-year follow up,
      406 suicidal deaths were recorded. Men living without a spouse and women living
      with a parent(s) only were at increased risk of suicide than those living with a
      spouse only. The multivariate HR (95% CI) in men were as follows: "living with a
      parent(s) only", 1.86 (1.03-3.36); "living with a child(ren) only", 2.20 (1.32
      3.66); "living with a parent(s) and child(ren)", 1.95 (1.02-3.72); and "living
      alone", 1.80 (0.99-3.25); and in women was as follow "living with a parent(s)
      only", 3.80 (1.90-7.61). Suicide risk was significantly decreased among women
      living with a spouse and child(ren) as compared with women living with a spouse
      only (HR 0.58, 95%CI 0.34 to 0.98). CONCLUSIONS: Men living without a spouse and
      women living with a parent(s) only were at increased risk of suicide. Women
      living together with a spouse and child(ren) were at decreased risk of suicide.

PMID- 21168919
TI  - No influence of PTGS2 polymorphisms on response and remission to antidepressants
      in major depression.
AB  - In the present study, aimed at investigating whether a set of single nucleotide
      polymorphisms (SNPs) within PTGS2 gene (rs4648276, rs2066826 and rs689466) could
      be associated with antidepressant response, remission and treatment resistance in
      a sample of major depression patients, we did not find evidence supporting any of
      such associations.

PMID- 21168920
TI  - Early response to antipsychotic therapy as a clinical marker of subsequent
      response in the treatment of patients with first-episode psychosis.
AB  - Early response to antipsychotic medication has been shown to accurately predict
      later response to continued use of the same treatment in patients with chronic
      schizophrenia. This study examines whether this predictive pattern exists for
      patients with first-episode psychosis. We used a data-driven threshold for early
      response of >= 26.2% improvement from baseline on the Positive and Negative
      Syndrome Scale (PANSS(0-6)) Total score to determine whether response at Week 2
      of treatment may predict response at Week 12 in a randomized, double-blind trial
      of olanzapine versus haloperidol for treatment of patients with first-episode
      psychosis (N=225). Later response was defined as a >= 40% and >= 50% improvement
      in PANSS Total(0-6) score and as remission. At Week 2, 43% (97/225) of patients
      were identified as early responders. At a threshold for later response of >= 50%
      improvement in PANSS(0-6) Total score, early non-response most strongly predicted
      later non-response, demonstrating high specificity (74%) and high negative
      predictive value (80%). As had been seen in the treatment of patients with
      chronic schizophrenia, early non-response was a robust predictor of subsequent
      non-response in the treatment of patients with first-episode psychosis.

PMID- 21168921
TI  - Skin-infiltrating T cells and cytokine expression in Icelandic horses affected
      with insect bite hypersensitivity: a possible role for regulatory T cells.
AB  - Equine insect bite hypersensitivity (IBH) is a seasonally recurrent, pruritic
      skin disorder caused by an IgE-mediated reaction to salivary proteins of biting
      flies, predominantly of the genus Culicoides. The aim of this study was to define
      T cell subsets and cytokine profile in the skin of IBH-affected Icelandic horses
      with particular focus on the balance between T helper (Th) 1, Th2 and T
      regulatory (Treg) cells. Distribution and number of CD4+, CD8+ and Forkhead box
      P3 (FoxP3)+ T cells were characterized by immunohistochemical staining in
      lesional and non-lesional skin of moderately and severely IBH-affected horses
      (n=14) and in the skin of healthy control horses (n=10). Using real-time
      quantitative reverse transcription-polymerase chain reaction, mRNA expression
      levels of Th2 cytokines (Interleukin (IL)-4, IL-5, IL-13), Th1 cytokines
      (Interferon-gamma), regulatory cytokines (Transforming Growth Factor beta1, IL
      10) and the Treg transcription factor FoxP3 were measured in skin and blood
      samples. Furthermore, Culicoides nubeculosus specific serum IgE levels were
      assessed. Lesions of IBH-affected horses contained significantly higher numbers
      of CD4+ cells than skin of healthy control horses. Furthermore, the total number
      of T cells (CD4+ and CD8+) was significantly increased in lesional compared to
      non-lesional skin and there was a tendency (p=0.07) for higher numbers of CD4+
      cells in lesional compared to non-lesional skin. While the number of FoxP3+ T
      cells did not differ significantly between the groups, the ratio of Foxp3 to CD4+
      cells was significantly lower in lesions of severely IBH-affected horses than in
      moderately affected or control horses. Interestingly, differences in FoxP3
      expression were more striking at the mRNA level. FoxP3 mRNA levels were
      significantly reduced in lesional skin, compared both to non-lesional and to
      healthy skin and were also significantly lower in non-lesional compared to
      healthy skin. Expression levels of IL-13, but not IL-4 or IL-5, were
      significantly elevated in lesional and non-lesional skin of IBH-affected horses.
      IL-10 levels were lower in lesional compared to non-lesional skin (p=0.06) and
      also lower (p=0.06) in the blood of IBH-affected than of healthy horses. No
      significant changes were observed regarding blood expression levels of Th1 and
      Th2 cytokines or FoxP3. Finally, IBH-affected horses had significantly higher
      Culicoides nubeculosus specific serum IgE levels than control horses. The
      presented data suggest that an imbalance between Th2 and Treg cells is a
      characteristic feature in IBH. Treatment strategies for IBH should thus aim at
      restoring the balance between Th2 and Treg cells.

PMID- 21168922
TI  - Reduced thymic expression of ErbB receptors without auto-antibodies against
      synaptic ErbB in myasthenia gravis.
AB  - In myasthenia gravis (MG), the neuromuscular transmission is impaired mainly by
      auto-antibodies against the acetylcholine receptor (AChR) or MuSK. In about 5% of
      the MG patients, however, the auto-antigen is still unknown. We investigated
      whether these idiopathic MG patients (iMG) have auto-antibodies against ErbB
      proteins, which influence the AChR density at the NMJ. Our results show reduced
      mRNA expression levels of ErbB4 in thymus tissue of iMG patients compared to AChR
      MG and non-MG patients, but we could not detect anti-ErbB antibodies in sera of
      iMG patients. Therefore, our results do not support a role for ErbB receptors as
      auto-antigens in iMG patients.

PMID- 21168923
TI  - Comparison of peritonsillar levobupivacaine and bupivacaine infiltration for post
      tonsillectomy pain relief in children: placebo-controlled clinical study.
AB  - OBJECTIVES: To compare the effects of preincisional peritonsillar infiltration of
      levobupivacaine and bupivacaine on post-tonsillectomy pain in children. METHODS:
      Sixty children undergoing elective tonsillectomy or adenotonsillectomy were
      randomly allocated into three groups before tonsillectomy: peritonsillar
      infiltrations with 0.25% levobupivacaine with 1:200,000 epinephrine (group
      levobupivacaine, n=20), 0.25% bupivacaine with 1:200,000 epinephrine (group
      bupivacaine, n=20), and normal saline (group saline, n=20) were applied. Pain was
      evaluated by using a modified Children's Hospital of Eastern Ontario Pain Scale
      (mCHEOPS). Choice of additional analgesic was acetaminophen for all patients.
      RESULTS: mCHEOPS values at 0th (immediately) and 30th minute after arrival the
      PACU were lower in both the local anesthetics groups than the saline group
      (p<0.001, p<0.01 for the group levobupivacaine; p<0.001, p<0.05 for the group
      bupivacaine, respectively). In addition, mCHEOPS values at 1st hour in the ward
      was lower in the group bupivacaine when compared to the group saline (p<0.05).
      Analgesic requirements and the time to first analgesia required, were also
      significantly different between the local anesthetic and saline groups (p<0.05
      for both local anesthetics groups). Time to first mobilization was shorter in
      both local anesthetic groups when compared to the saline group (p<0.05 for both
      local anesthetic groups). CONCLUSION: Preincisional peritonsillar infiltration
      with levobupivacaine or bupivacaine before tonsillectomy, are effective than
      saline, in reducing early post-tonsillectomy pain, where as bupivacaine had
      slightly longer effect. Compared to saline, with both anesthetic infiltrations,
      lesser medication for analgesia is required. The clinical trial registration
      number (Research Ethics Committee of Medical Faculty, Uludag University): 2008
      4/36, 19 February 2008.

PMID- 21168924
TI  - Oral health status and treatment requirements of different residential homes in
      Istanbul: a comparative study.
AB  - The purpose of this study was to investigate dental/denture status of the elderly
      people living in different residential homes. In 346 elderly people from
      different residential homes two belonging to the state (Group 1 and Group 2) and
      one supported by private foundations (Group 3) were examined. Sixty percent of
      participants were edentulous and 22.8% of participants had no complete dentures
      which 9 (7.4%) of them were in Groups 1 and 2. Over 50% of the participants had
      no or low income and 45% of participants were illiterate. All of the participants
      who were illiterate and had low income were in Group 1 and Group 2. Oral hygiene
      was good for 15.4% and only 19.4% of participants removed their dentures
      overnight. Denture stomatitis was observed in 61.7% of subjects. Significant
      correlation was found between denture hygiene and age of participant, general
      health status, denture stomatitis, and overnight denture wear (p=0.001). The
      decayed, missing and filled teeth (DMFT) scores were 25.52+/-3.37. There was
      statistically significant differences between groups for DMFT scores (p=0.016).
      Dental health education is also needed focusing on the special needs of this
      neglected and socioeconomically deprived population to improve their quality of
      life.

PMID- 21168925
TI  - Cardiac surgery in nonagenarians: pushing the boundary one further decade.
AB  - With increasing age of the general population, the necessity for cardiac surgery
      in the collective of patients aged 90 and older has been increasing. To aid in
      the choice of adequate therapy we investigated our experience for the group of
      nonagenarians undergoing surgical interventions. From 6/2000 to 9/2007, 17
      patients aged 90 and older underwent open-heart surgery at our institution. We
      performed a retrospective data analysis including baseline preoperative clinical
      status, intra- and postoperative results and the long-term survival in the
      further postoperative course. We performed cardiac surgical procedures in 17
      patients (male/female ratio 6/11), including isolated aortic valve replacement (n
      = 7), aortic root replacement (n = 2), isolated coronary bypass surgery (n = 4),
      combined coronary and valve surgery (n = 5), re-operative valve replacement (n =
      1) and root replacement with arch repair (n = 1). Emergency procedures were
      performed in 11.8% (2/17). Mean age was 91.9 +/- 1.2 years, ranging 90.1-94.2.
      Mean follow-up was 3.2 +/- 2.2 years. The 30-day mortality was 17.6% (3/17),
      overall mortality at 42.9 follow-up patient years was 58.8% (10/17). We conclude
      that cardiac surgery procedures can be performed with therapeutic benefit for
      selected nonagenarians safely and with acceptable operative risk. After analysis
      our clinical experience we believe age alone not to be a contraindication for
      surgical intervention, consideration of the physiologic status of the patient
      reflects on the postoperative outcome. Survival of the patients investigated that
      survived the initial 30-day postoperative period was similar to the estimated
      survival of the equally aged general population in Germany.

PMID- 21168926
TI  - Evaluation of the peri-strut low intensity area following sirolimus- and
      paclitaxel-eluting stents implantation: insights from an optical coherence
      tomography study in humans.
AB  - BACKGROUND: Recent pathological studies have demonstrated that peri-strut low
      intensity area (PLIA) seen on optical coherence tomography (OCT) imaging
      represents the presence of fibrinogen and/or extracellular matrix. We sought to
      assess the clinical prevalence of PLIA and its relation to neointimal
      proliferation after the implantation of sirolimus- (SES) and paclitaxel-eluting
      stents (PES) in humans. METHODS: Seventy patients underwent 6-months follow-up
      OCT after SES (43 stents) or PES (37 stents) implantation. PLIA was defined as a
      region around stent struts with homogenous lower intensity than surrounding
      tissue on OCT images without signal attenuation. The incidence of stent struts
      with PLIA (+PLIA struts) was calculated as the number of +PLIA struts/number of
      all struts (%). RESULTS: PES showed a higher incidence of stents with PLIA than
      SES (86% vs. 58%; p=0.005) with a higher prevalence of +PLIA struts (27.8+/-21.9%
      vs. 10.9+/-11.0%; p=0.0008). SES with PLIA showed a significantly greater
      neointimal thickness (NIT) than SES without PLIA (p=0.02), while PES showed a
      similar tendency (p=0.19). In a detailed strut basis analysis, average NIT on
      +PLIA struts were significantly greater than that on -PLIA struts in both SES and
      PES. In addition, average NIT was positively correlated with the prevalence of
      +PLIA struts (SES: Rho=0.73; p<0.0001, PES: Rho=0.58, p=0.0005) in both stents.
      CONCLUSIONS: The prevalence of PLIA was significantly higher in PES than in SES.
      The presence and extent of PLIA might be associated with intimal thickening after
      1st-generation DES implantation.

PMID- 21168927
TI  - Concurrent chemoradiotherapy with 5-fluorouracil and mitomycin C for anal
      carcinoma: are there differences between HIV-positive and HIV-negative patients
      in the era of highly active antiretroviral therapy?
AB  - PURPOSE: To report treatment compliance, toxicity and clinical outcome of
      chemoradiotherapy (CRT) for anal carcinoma in HIV-negative vs. HIV-positive
      patients treated with highly active antiretroviral therapy. MATERIAL AND METHODS:
      Between 1997 and 2008, 25 HIV-positive and 45 HIV-negative patients received CRT
      (50.4 Gy at 1.8 Gy/fraction plus 5.4-10.8 Gy boost; 5-fluorouracil, 1000 mg/m(2),
      Days 1-4 and 29-32, mitomycin C, 10 mg/m(2), Days 1 and 29). Median follow-up was
      51 (range, 3-235) months. RESULTS: HIV-positive patients were significantly
      younger (mean age, 47 vs. 57 years, p<0.001) and predominantly male (92% vs. 29%,
      p<0.001). CRT could be completed in all patients with a reduction of chemotherapy
      and/or RT-interruption in 28% and 8%, respectively, in HIV-positive patients, and
      in 9% and 11%, respectively, in HIV-negative patients. Acute Grade 3/4-toxicity
      occurred in 44% vs. 49% (p=0.79). Initial complete response (84% vs. 93%,
      p=0.41), 5-year rates of local control (65% vs. 78%, p=0.44), cancer-specific
      (78% vs. 90%, p=0.17) and overall survival (71% vs. 77%, p=0.76) were not
      significantly different. CONCLUSION: HIV-positive patients with anal cancer can
      be treated with standard CRT, with the same tolerability and toxicity as HIV
      negative patients. Long-term local control and survival rates are not
      significantly different between these groups.

PMID- 21168928
TI  - Effect of stride frequency on the energy cost of walking in obese teenagers.
AB  - The aim of this study was to compare the energy cost of obese and non-obese
      teenagers while walking at their preferred speed and different stride
      frequencies. Twelve obese and twelve non-obese teenagers walked continuously on
      the treadmill at their most comfortable speed for 6 periods of 4 min each. Each
      period corresponded to a specific stride frequency: preferred (PSF), force-driven
      harmonic oscillator (FDHO), PSF+10%, PSF+20%, PSF-10% and PSF-20%.
      Cardiorespiratory parameters were collected between the 3rd and 4th minute of
      each stage, and used to calculate the energy cost of walking (EC). The main
      results showed a significantly higher cost of walking expressed relative to lean
      body mass. In addition, a U-shaped relationship between EC and stride frequency
      was shown in both groups, with PSF and FDHO leading to a significantly lower
      value compared to all other frequencies. This showed first, that FDHO is a good
      predictor of PSF and minimal energy cost of walking in both groups, and second,
      that excess body fat does not affect the relationship between energy expenditure
      and stride frequency. Walking at lower or higher than preferred frequencies could
      be used as an exercise mode to promote weight loss in obese teenagers.

PMID- 21168930
TI  - Individual responsibility and health-risk behaviour: a contingent valuation study
      from the ex ante societal perspective.
AB  - This study analyzes peoples' social preferences for individual responsibility to
      health-risk behaviour in health care using the contingent valuation method
      adopting a societal perspective. We measure peoples' willingness to pay for
      inclusion of a treatment in basic health insurance of a hypothetical lifestyle
      dependent (smoking) and lifestyle independent (chronic) health problem. Our
      hypothesis is that peoples' willingness to pay for the independent and the
      dependent health problems are similar. As a methodological challenge, this study
      also analyzes the extent to which people consider their personal situation when
      answering contingent valuation questions adopting a societal perspective. 513
      Dutch inhabitants responded to the questionnaire. They were asked to state their
      maximum willingness to pay for inclusion of treatments in basic health insurance
      package for two health problems. We asked them to assume that one hypothetical
      health problem was totally independent of behaviour (for simplicity called
      chronic disease). Alternatively, we asked them to assume that the other
      hypothetical health problem was totally caused by health-risk behaviour (for
      simplicity called smoking disease). We applied the payment card method to guide
      respondents to answer the contingent valuation method questions. Mean willingness
      to pay was 42.39 Euros (CI=37.24-47.55) for inclusion of treatment for health
      problem that was unrelated to behaviour, with '5-10' and '10-20 Euros' as most
      frequently stated answers. In contrast, mean willingness to pay for inclusion
      treatment for health-risk related problem was 11.29 Euros (CI=8.83-14.55), with
      '0' and '0-5 Euros' as most frequently provided answers. Difference in mean
      willingness to pay was substantial (over 30 Euros) and statistically significant
      (p-value=0.000). Smokers were statistically significantly more (p-value<0.01)
      willing to pay for the health-risk related (smoking) problem compared with non
      smokers, while people with chronic condition were not willing to pay more for the
      health-risk unrelated (chronic) problem than people without chronic condition.
      This suggests that sub groups of people might differ in terms of abstracting from
      their personal situation when answering valuation questions from a societal
      perspective.

PMID- 21168929
TI  - Auditory instructional cues benefit unimanual and bimanual drawing in Parkinson's
      disease patients.
AB  - The present study investigated performance of unimanual and bimanual anti-phase
      and in-phase upper limb line drawing using three different types of cues. Fifteen
      Parkinson's disease (PD) patients, 15 elderly, and 15 young adults drew lines
      away from and towards their body on a tabletop every 1000 ms for 30 s under three
      different cueing conditions: (1) verbal ('up', 'down'); (2) auditory (high tone,
      low tone); (3) visual (target line switched from top to bottom). PD patients had
      larger and more variable amplitudes which may be related to the finding that they
      also produced more curvilinear movements than young and elderly adults.
      Consistent with previous research, when compared to the elderly and young adult
      group PD patients produced a mean relative phase which deviated more from the
      instructed coordination modes and they showed larger variability of relative
      phase in bimanual coordination, especially in anti-phase conditions. For all
      groups, auditory and verbal cues resulted in lower coefficient of variance of
      cycle time, lower variability of amplitude and lower variability of relative
      phase than visual cues. The benefit of auditory cues may be related to the timing
      nature of the task or factors related to the auditory cues (e.g., reduced
      attentional demands, more kinesthetic focus).

PMID- 21168931
TI  - Guatemala: the economic burden of illness and health system implications.
AB  - OBJECTIVES: To assess the economic burden of ill health in Guatemala, the
      characteristics of Guatemala's health system that potentially explain this
      burden, and to identify policies to help ameliorate it. METHODS: Data from the
      2000 and 2006 Living Standard Measurement Surveys are used to assess levels of
      financial burden from ill health, along with information on health system
      characteristics of Guatemala and recent reform experiences of several middle- and
      low-income countries. RESULTS: Despite some gains over the period from 2000 to
      2006, there continues to be both a high level and inequitable distribution of
      financial burden associated with ill health in Guatemala. Low levels of insurance
      coverage, a heavy concentration of the uninsured among the less well off and
      rural populations, as well as their low levels of access to public services are
      important drivers of out of pocket spending on health. Households with older
      members also appear to be at increased risk for out of pocket payments.
      CONCLUSIONS: High levels of catastrophic health spending and poverty co-exist
      with significant economic inequality and poverty in Guatemala. With health system
      features and a large informal sector similar to many other developing countries,
      recent international experience can provide useful lessons to help Guatemala
      devise innovative financing and payment mechanisms to address these concerns.

PMID- 21168932
TI  - Expanding health insurance to increase health care utilization: will it have
      different effects in rural vs. urban areas?
AB  - OBJECTIVES: This study investigates the importance of medical fee and distance to
      health care provider on individual's decision to seek care in developing
      countries. METHODS: The estimation method used a mixed logit model applied to
      data from the third wave of the Indonesian family life survey (2000). The key
      variables of interest include medical fee and distance to different types of
      health care provider and individual characteristic variables. RESULTS: Urban
      dweller's decision to choose health care providers are sensitive to the monetary
      cost of medical care as measured by medical fee but they are not sensitive to
      distance. For those who reside in rural area, they are sensitive to the non
      medical component cost of care as measured by travel distance but they are not
      sensitive to medical fee. CONCLUSIONS: As a result of those findings, policy
      makers should consider different sets of policy instruments when attempting to
      expand health service's usage in urban and rural areas of Indonesia. To increase
      access in urban areas, we recommend expansion of health insurance coverage in
      order to lower out-of-pocket medical expenditures. As for rural areas, expansion
      of medical infrastructures to reduce commuting distance and costs will be needed
      to increase utilization.

PMID- 21168934
TI  - A reckoning for reckoning.

PMID- 21168933
TI  - EGFR and EML4-ALK gene mutations in NSCLC: a case report of erlotinib-resistant
      patient with both concomitant mutations.
AB  - The fusion gene EML4-ALK (echinoderm microtubule-associated protein-like 4 gene
      and the anaplastic lymphoma kinase gene) was recently identified as a novel
      genetic alteration in non-small cell lung cancer (NSCLC). EML4-ALK translocations
      correlate with specific clinical and pathological features, in particular lack of
      EGFR and K-ras mutations, and may be associated with resistance to EGFR tyrosine
      kinase inhibitors (TKIs). Here, we report a case of a patient with a concomitant
      EGFR mutation and ALK translocation resistant to erlotinib. Considering this
      report, ALK status should be investigated in unexplained cases of EGFR-TKI
      resistance of EGFR mutated NSCLCs.

PMID- 21168935
TI  - Tyrosine phosphorylation of VE-cadherin and claudin-5 is associated with TGF
      beta1-induced permeability of centrally derived vascular endothelium.
AB  - Breakdown of the inner blood-retinal barrier and the blood-brain barrier is
      associated with changes in tight and adherens junction-associated proteins that
      link vascular endothelial cells. This study aimed to test the hypothesis that
      transforming growth factor (TGF)-beta1 increases the paracellular permeability of
      vascular endothelial monolayers through tyrosine phosphorylation of VE-cadherin
      and claudin-5. Bovine retinal and human brain capillary endothelial cells were
      grown as monolayers on coated polycarbonate membranes. Paracellular permeability
      was studied by measuring the equilibration of (14)C-inulin or fluorescence
      labelled dextran. Changes in VE-cadherin and claudin-5 expression were studied by
      immunocytochemistry (ICC) and quantified by cell-based enzyme linked
      immunosorbent assays (ELISA). Tyrosine phosphorylation of VE-cadherin and claudin
      5 was studied by ICC, immunoprecipitation and Western blotting. We found that
      exposure of endothelial cells to TGF-beta1 caused a dose-dependent increase in
      paracellular permeability as reflected by increases in the equilibration of (14)C
      inulin. This effect was enhanced by the tyrosine phosphatase inhibitor
      orthovanadate and attenuated by the tyrosine kinase inhibitor lavendustin A. ICC
      and cell-based ELISA revealed that TGF-beta1 induced both dose- and time
      dependent decreases in VE-cadherin and claudin-5 expression. Assessment of cell
      viability indicated that changes in these junction-associated proteins were not
      due to endothelial death or injury. ICC revealed that tyrosine phosphorylation of
      endothelial monolayers was greatly enhanced by TGF-beta1 treatment, and
      immunoprecipitation of cell lysates showed increased tyrosine phosphorylation of
      VE-cadherin and claudin-5. Our results suggest that tyrosine phosphorylation of
      VE-cadherin and claudin-5 is involved in the increased paracellular permeability
      of central nervous system-derived vascular endothelium induced by TGF-beta1.

PMID- 21168936
TI  - [Cerebellar hemorrhage secondary to cerebrospinal fluid leak after lumbar canal
      surgery].

PMID- 21168937
TI  - [A case report of ciguatera fish poisoning in a traveller to Dominican Republic].

PMID- 21168938
TI  - Accidental use of alcohol during arthrocentesis of the temporomandibular joint.

PMID- 21168939
TI  - How to select the best tree planting locations to enhance air pollution removal
      in the MillionTreesNYC initiative.
AB  - Highest priority zones for tree planting within New York City were selected by
      using a planting priority index developed combining three main indicators:
      pollution concentration, population density and low canopy cover. This new tree
      population was projected through time to estimate potential air quality and
      carbon benefits. Those trees will likely remove more than 10,000 tons of air
      pollutants and a maximum of 1500 tons of carbon over the next 100 years given a
      4% annual mortality rate. Cumulative carbon storage will be reduced through time
      as carbon loss through tree mortality outweighs carbon accumulation through tree
      growth. Model projections are strongly affected by mortality rate whose
      uncertainties limit estimations accuracy. Increasing mortality rate from 4 to 8%
      per year produce a significant decrease in the total pollution removal over a 100
      year period from 11 000 tons to 3000 tons.

PMID- 21168940
TI  - The impact of EDTA on lead distribution and speciation in the accumulator Sedum
      alfredii by synchrotron X-ray investigation.
AB  - The in vivo localization and speciation of lead (Pb) in tissues of the
      accumulator Sedum alfredii grown in EDTA-Pb and Pb(NO(3))(2) was studied by
      synchrotron X-ray investigation. The presence of EDTA-Pb in solution resulted in
      a significant reduction of Pb accumulation in S. alfredii. Lead was
      preferentially localized in the vascular bundles regardless of treatments but the
      intensities of Pb were lower in the plants treated with EDTA. Lead was
      predominantly presented as a Pb-cell wall complex in the plants regardless of its
      supply form. However, a relatively high proportion of Pb was observed as Pb-EDTA
      complex when the plant was treated with EDTA-Pb, but as a mixture of
      Pb(3)(PO(4))(2), Pb-malic, and Pb-GSH when cultured with ionic Pb. These results
      suggest that EDTA does not increase the internal mobility of Pb, although the
      soluble Pb-EDTA complex could be transported and accumulated within the plants of
      S. alfredii.

PMID- 21168941
TI  - The effects of pruning and nodal adventitious roots on polychlorinated biphenyl
      uptake by Cucurbita pepo grown in field conditions.
AB  - Two cultivation techniques (i-pruning and ii-nodal adventitious root
      encouragement) were investigated for their ability to increase PCB
      phytoextraction by Cucurbita pepo ssp pepo cv. Howden (pumpkin) plants in situ at
      a contaminated industrial site in Ontario (Aroclor 1248, mean soil [PCB] = 5.6
      MUg g(-1)). Pruning was implemented to increase plant biomass close to the root
      where PCB concentration is known to be highest. This treatment was found to have
      no effect on final shoot biomass or PCB concentration. However, material pruned
      from the plant is not included in the final shoot biomass. The encouragement of
      nodal adventitious roots at stem nodes did significantly increase the PCB
      concentration in the primary stem, while not affecting shoot biomass. Both
      techniques are easily applied cultivation practices that may be implemented to
      decrease phytoextraction treatment time.

PMID- 21168942
TI  - Spatiotemporal dynamics of spring and stream water chemistry in a high-mountain
      area.
AB  - The present study deals with the application of the self-organizing map (SOM)
      technique in the exploration of spatiotemporal dynamics of spring and stream
      water samples collected in the Chocholowski Stream Basin located in the Tatra
      Mountains (Poland). The SOM-based classification helped to uncover relationships
      between physical and chemical parameters of water samples and factors determining
      the quality of water in the studied high-mountain area. In the upper part of the
      Chocholowski Stream Basin, located on the top of the crystalline core of the
      Tatras, concentrations of the majority of ionic substances were the lowest due to
      limited leaching. Significantly higher concentration of ionic substances was
      detected in spring and stream samples draining sedimentary rocks. The influence
      of karst-type springs on the quality of stream water was also demonstrated.

PMID- 21168943
TI  - Development and results of a kidney disease knowledge survey given to patients
      with CKD.
AB  - BACKGROUND: Little is known about disease-specific knowledge in patients with
      chronic kidney disease (CKD). We developed and examined the results of a survey
      to characterize kidney disease knowledge. DESIGN: Survey about kidney disease
      knowledge, with questions developed by experts. SETTING & PARTICIPANTS: 401 adult
      patients with CKD (stages 1-5) attending a nephrology clinic from April-October
      2009. OUTCOMES & MEASUREMENTS: We calculated survey reliability using the Kuder
      Richardson-20 coefficient and established construct validity by testing a priori
      hypotheses of associations between survey results and patient characteristics. We
      descriptively analyzed survey responses and applied linear regression analyses to
      evaluate associations with patient characteristics. Health literacy was measured
      using the Rapid Estimate of Adult Literacy in Medicine. RESULTS: Participants'
      median age was 58 (25th-75th percentile, 46-68) years, 83% were white, 18% had
      limited literacy, and 77% had CKD stages 3-5. The 28-question knowledge survey
      had good reliability (Kuder-Richardson-20 coefficient = 0.72), and mean knowledge
      score was 66% +/- 15% (SD). In support of the construct validity of our knowledge
      survey, bivariate analysis shows that scores were associated with age (beta = 
      0.01/10 years; 95% CI, -0.02 to -0.005; P = 0.003), formal education (beta =
      0.09; 95% CI, 0.03-0.15; P = 0.004), health literacy (beta = 0.06; 95% CI, 0.03
      0.10; P = 0.001), kidney education class participation (beta = 0.05; 95% CI, 0.01
      0.09; P = 0.009), knowing someone else with CKD (beta = 0.05; 95% CI, 0.02-0.08;
      P = 0.001), and awareness of one's own CKD diagnosis (beta = 0.07; 95% CI, 0.04
      0.10; P < 0.001). Findings were similar in adjusted analyses. LIMITATIONS:
      Recruitment from 1 clinic limits generalizability of findings. CONCLUSIONS: For
      patients with CKD, this Kidney Knowledge Survey (KiKS) is reliable and valid and
      identifies areas of and risk factors for poor kidney knowledge. Further study is
      needed to determine the impact of CKD knowledge on self-care behaviors and
      clinical outcomes.

PMID- 21168944
TI  - Surrogate markers of cardiovascular disease in CKD: what's under the hood?
AB  - Although clinical cardiovascular outcomes, such as heart attack, stroke, and
      sudden cardiac death, have a dramatic onset, they result from prolonged exposure
      to an ever-growing array of risk factors. Several noninvasive procedures are
      available to assess the cumulative effect of these exposures with the goal of
      more precisely estimating a person's cardiovascular risk. These include ankle
      brachial index, which provides an estimation of obstruction in major-vessel lumen
      caliber; carotid ultrasound, which evaluates carotid intima-media thickness and
      plaque, visibly quantifying atherosclerotic burden; aortic pulse wave velocity,
      which provides a measure of large-artery stiffness; and echocardiography, which
      measures left ventricular mass, providing a measure of subclinical hypertensive
      heart disease. In this narrative review, we discuss the role of each of these
      measures, with a particular emphasis on patients with chronic kidney disease.

PMID- 21168946
TI  - Palliative care in CKD: the earlier the better.

PMID- 21168945
TI  - Clinical features and outcomes of anti-glomerular basement membrane disease in
      older patients.
AB  - BACKGROUND: Anti-glomerular basement membrane (GBM) disease is being recognized
      increasingly in older patients. Disease presentation and outcomes of these
      patients are unclear. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 221
      consecutive Chinese patients with anti-GBM disease diagnosed in 1998-2008 in our
      tertiary referral center. Anti-GBM disease was defined as positive anti-GBM
      antibodies in circulation and/or linear immunoglobulin G deposition along the GBM
      on kidney biopsy. PREDICTOR: Older age, defined as 65 years or older, and
      antineutrophil cytoplasmic antibody, detected using immunofluorescence and enzyme
      linked immunosorbent assay, at presentation. OUTCOMES: Clinical features, kidney
      pathologic characteristics, end-stage renal disease (ESRD), and mortality.
      Multivariate Cox proportional hazard models were used to assess the contribution
      of age, sex, clinical measures, and treatments to ESRD and mortality. RESULTS: 50
      of 221 (22.6%) patients were 65 years or older. Older patients had a male
      predominance (male/female ratio, 1.9:1). They had a higher proportion of positive
      antineutrophil cytoplasmic antibody results (46.0% vs 14.6%; P < 0.001), lower
      prevalence of hemoptysis (26.0% vs 46.2%; P = 0.01), lower urine protein
      excretion (1.4 +/- 1.0 vs 3.9 +/- 3.3 g/d; P = 0.001), and higher estimated
      glomerular filtration rate (eGFR) at presentation (8.4 vs 5.1 mL/min/1.73 m(2); P
      = 0.007) compared with younger patients. During follow-up, 30 of 37 (81.1%) and
      21 of 37 (56.8%) patients developed ESRD and died in the older group compared
      with 115 of 139 (82.7%) and 35 of 139 (25.2%) in the younger group (P = 0.1 and P
      = 0.001, respectively). For older patients, multivariate Cox regression analysis
      showed that higher initial eGFR was an independent predictor for both ESRD (HR,
      0.86; 95% CI, 0.78-0.96; P = 0.005) and death (HR, 0.79; 95% CI, 0.66-0.94; P =
      0.008). LIMITATIONS: Not all patients underwent kidney biopsy, especially those
      with very old age or ESRD at presentation. CONCLUSIONS: Older patients with anti
      GBM disease had milder kidney damage and less pulmonary involvement. Outcomes
      were predicted by initial eGFR. Thus, early diagnosis was crucial to improve
      outcomes.

PMID- 21168947
TI  - Minocycline neuroprotection in a rat model of asphyxial cardiac arrest is
      limited.
AB  - OBJECTIVE: The study investigated a possible neuroprotective potency of
      minocycline in an experimental asphyxial cardiac arrest (ACA) rat model.
      Clinically important survival times were evaluated thus broadening common
      experimental approaches. METHODS: Adult rats were subjected to 5 min of ACA
      followed by resuscitation. There were two main treatment groups: ACA and sham
      operated. Relating to minocycline treatment each group consisted of three sub
      groups: pre-, post-, and sans-mino, with three different survival times: 4, 7,
      and 21 days. Neurodegeneration and microgliosis were monitored by
      immunohistochemistry. Alterations of microglia-associated gene expression were
      analyzed by quantitative RT-PCR. RESULTS: ACA induced massive nerve cell loss and
      activation of microglia/macrophages in hippocampal CA1 cell layer intensifying
      with survival time. After 7 days, minocycline significantly decreased both,
      neuronal degeneration and microglia response in dependence on the application
      pattern; application post ACA was most effective. After 21 days, neuroprotective
      effects of minocycline were lost. ACA significantly induced expression of the
      microglia-associated factors Ccl2, CD45, Mac-1, F4-80, and Tnfa. Independent on
      survival time, minocycline affected these parameters not significantly.
      Expression of iNOS was unaffected by both, ACA and minocycline. CONCLUSIONS: In
      adult rat hippocampus microglia was significantly activated by ACA. Minocycline
      positive affected neuronal survival and microglial response temporary, even when
      applied up to 18 h after ACA, thus defining a therapeutically-relevant time
      window. As ACA-induced neuronal cell death involves acute and delayed events,
      longer minocycline intervention targeting also secondary injury cascades should
      manifest neuroprotective potency, a question to be answered by further
      experiments.

PMID- 21168949
TI  - Gastropod nacre: structure, properties and growth--biological, chemical and
      physical basics.
AB  - The biogenic polymer/mineral composite nacre is a non-brittle biological ceramic,
      which self-organizes in aqueous environment and under ambient conditions. It is
      therefore an important model for new sustainable materials. Its highly controlled
      structural organization of mineral and organic components at all scales down to
      the nano- and molecular scales is guided by organic molecules. These molecules
      then get incorporated into the material to be responsible for properties like
      fracture mechanics, beauty and corrosion resistance. We report here on structure,
      properties and growth of columnar (gastropod) nacre with emphasis on the genus
      Haliotis in contrast to sheet nacre of many bivalves.

PMID- 21168948
TI  - Ondansetron attenuates hepatic injury via p38 MAPK-dependent pathway in a rat
      haemorrhagic shock model.
AB  - BACKGROUND: Ondansetron is a 5-HT3 receptor antagonist with potent antiemetic,
      analgesic, and antiphlogistic effects. Recent evidence suggests that the co
      existence of 5-HT3 receptors in various cell types is involved in inflammation.
      However, the effects that 5-HT3 antagonists produce in haemorrhagic shock and
      resuscitation remain unknown. In this study, we hypothesized that ondansetron
      administration in male rats, after haemorrhagic shock, decreases cytokine
      production and protects against hepatic injury through a p38 mitogen-activated
      protein kinase (MAPK) pathway. METHODS: Male Sprague-Dawley rats underwent
      haemorrhagic shock (mean arterial blood pressure 40 mm Hg for 90 min), followed
      by resuscitation. Various doses of ondansetron (0.1, 0.3, 1, 3 mg kg(-1)) or a
      single dose of ondansetron (1 mg kg(-1)) with or without a p38 MAPK inhibitor (SB
      203580, 2 mg kg(-1)) or vehicle were administered intravenously during
      resuscitation. Plasma aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT) concentrations and various liver proinflammatory
      parameters were measured at 24h after resuscitation. RESULTS: Results show that
      haemorrhagic shock increases plasma AST and ALT concentrations, hepatic
      myeloperoxidase activity, cytokine-induced neutrophil chemoattractant (CINC)-1,
      CINC-3, intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6) and
      tumor necrosis factor alpha (TNF-alpha) levels. These parameters were
      significantly improved in the ondansetron-treated rats subjected to haemorrhagic
      shock. Ondansetron treatment restored phos-p38 MAPK expression as compared with
      vehicle-treated haemorrhaged rats. Coadministration of SB-203580 prevented the
      beneficial effects of ondansetron on postresuscitation proinflammatory responses
      and hepatic injury. CONCLUSION: Ondansetron attenuates hepatic injury following
      haemorrhagic shock, which is, at least in part, to be due to its anti
      inflammatory effect via p38 MAPK signal pathway.

PMID- 21168950
TI  - Effects of a rock phosphate on indigenous rhizobia associated with Sesbania
      sesban.
AB  - Tilemsi rock phosphate (TRP) of Mali is one of the most promising rock phosphate
      in West Africa for soil fertilization, but it is little used because of its
      insoluble form. The main objective of this study is to investigate TRP effects on
      rhizobia associated with the multipurpose leguminous tree Sesbania sesban grown
      on a sandy soil, poor in phosphorus and not sterilised. The experiment included
      treatments with and without TRP and was conducted during 105 days. At the end,
      114 nodules have been collected and analysed by PCR/RFLP of 16S-23S intergenic
      spacer. Sixteen different RFLP profiles corresponding to different genomic groups
      of rhizobia have been detected. Five were dominant and present in both
      treatments. Five groups appear only in treatments without TRP whereas the six
      others are only in nodules of plants with TRP, suggesting a different capacity of
      natural phosphates solubilization by these strains.

PMID- 21168951
TI  - Antimuscarinic mechanisms and the overactive detrusor: an update.
AB  - CONTEXT: Antimuscarinics are the drugs of choice for the treatment of detrusor
      overactivity (DO) and overactive bladder (OAB) syndrome. However, the mechanisms
      for their beneficial effects have not yet been definitely established. OBJECTIVE:
      Literature available on the pathophysiologic aspects of storage symptoms and of
      antimuscarinic actions on the bladder was reviewed. EVIDENCE ACQUISITION: Medline
      was searched for the period ending October 2010 and included studies on human and
      animal tissues and animal models. Clinical studies exploring mechanisms involved
      in the effects of antimuscarinics were included. Searches were limited to the
      English language. EVIDENCE SYNTHESIS: Evidence for release of acetylcholine (ACh)
      from non-neuronal as well as neuronal sources during bladder filling has been
      demonstrated in isolated animal bladders as well as the human bladder.
      Urothelially derived ACh, probably via release of adenosine triphosphate, may
      stimulate afferent activity ("afferent noise") from the bladder contributing to
      OAB and DO. Afferent noise may also be generated by local ACh release within the
      detrusor muscle. This afferent activity can be inhibited by antimuscarinics at
      the low concentrations obtained with doses recommended for clinical use in
      OAB/DO. Within this therapeutic window, antimuscarinics may decrease OAB symptoms
      and DO without affecting the voiding contraction. Changes in muscarinic receptor
      functions have been demonstrated with aging and in different disorders associated
      with OAB/DO. CONCLUSIONS: ACh, derived from non-neuronal as well as neuronal
      sources and during bladder filling, directly or indirectly stimulates afferent
      activity from the bladder, contributing to OAB and DO. By inhibiting this effect,
      antimuscarinics may decrease OAB symptoms and DO without affecting the voiding
      contraction. Even if changes in muscarinic receptor functions may occur with
      aging and in different disorders associated with OAB/DO, such changes have not
      been shown convincingly to modify the beneficial effect of antimuscarinics in
      OAB/DO.

PMID- 21168952
TI  - Should all patients receive an immediate chemotherapeutic drug instillation after
      resection of papillary bladder tumors?

PMID- 21168953
TI  - 'Rare' infections mimicking multiple sclerosis: consider Lyme disease.

PMID- 21168954
TI  - Selective amygdalo-hippocampectomy as a potential trigger for disease progression
      in multiple sclerosis.

PMID- 21168956
TI  - Removal of cerium ions from aqueous solution by hydrous ferric oxide--a
      radiotracer study.
AB  - Radiotracer technique has been used to study the removal behavior of Ce (III)
      ions from aqueous solutions by synthesized and well characterized hydrous ferric
      oxide (HFO). Adsorptive concentration (10(-4)-10(-8) mol dm(-3)), pH (ca 4.0
      10.0) and temperature (303-333 K) were examined for assessing optimal conditions
      for removal of these ions. The uptake of Ce (III) ions, which fitted well for
      Freundlich and D-R isotherms, increased with increase in the temperature and no
      significant desorption took place in the studied temperature range. The presence
      of some anions/cations affected the uptake of metal ion markedly. Irradiation of
      hydrous ferric oxide and tungsten oxide by using a 11.1*10(9) Bq (Ra-Be) neutron
      source having a neutron flux of 3.9*10(6) cm(-2) s(-1) with associated gamma-dose
      rate of 1.72 Gy/h did not influence the extent of adsorption of Ce (III)
      significantly.

PMID- 21168957
TI  - Process control, energy recovery and cost savings in acetic acid wastewater
      treatment.
AB  - An anaerobic fixed bed loop (AFBL) reactor was applied for treatment of acetic
      acid (HAc) wastewater. Two pH process control concepts were investigated;
      auxostatic and chemostatic control. In the auxostatic pH control, feed pump is
      interrupted when pH falls below a certain pH value in the bioreactor, which
      results in reactor operation at maximum load. Chemostatic control assures
      alkaline conditions by setting a certain pH value in the influent, preventing
      initial reactor acidification. The AFBL reactor treated HAc wastewater at low
      hydraulic residence time (HRT) (10-12 h), performed at high space time loads (40
      45 kg COD/m(3) d) and high space time yield (30-35 kg COD/m(3) d) to achieve high
      COD (Chemical Oxygen Demand) removal (80%). Material and cost savings were
      accomplished by utilizing the microbial potential for wastewater neutralization
      during anaerobic treatment along with application of favourable pH-auxostatic
      control. NaOH requirement for neutralization was reduced by 75% and HRT was
      increased up to 20 h. Energy was recovered by applying costless CO(2) contained
      in the biogas for neutralization of alkaline wastewater. Biogas was enriched in
      methane by 4 times. This actually brings in more energy profits, since biogas
      extra heating for CO(2) content during biogas combustion is minimized and usage
      of other acidifying agents is omitted.

PMID- 21168958
TI  - Effects of liquid swine manure on dissipation of 17beta-estradiol in soil.
AB  - 17beta-estradiol (E2), a natural estrogenic hormone, degrades within hours and
      bind strongly to soils and sediments; however, estrogens are frequently detected
      in the environment at concentrations that impact water quality. Colloidal (COC)
      and dissolved (DOC) organic carbon may enhance the persistence and mobility of
      E2. Soil batch experiments were used to identify the persistence and sorption of
      radiolabeled E2 dissolved in solutions of (i) COC/DOC derived from liquid swine
      manure and (ii) CaCl(2). Estradiol disappeared from the aqueous phase before 7 d
      in the CaCl(2) solution, yet persisted throughout the duration of the 14 d
      experiment in the liquid manure solution. There was also concomitant formation of
      estrone (E1; a metabolite of E2) as E2 dissipated in sterile batch experiments,
      which was attributed to abiotic oxidation. The liquid manure solution appeared to
      interact with the estrogen and/or oxidation reaction sites, reducing E2
      degradation. Furthermore, the liquid manure solution reduced E2/E1 binding to the
      soil surface resulting in more E2/E1 in the aqueous layer compared to the CaCl(2)
      solution. Ultrafiltration results of liquid manure indicated that ~1/3 of E2 was
      associated with COC, which may be responsible for the reduced degradation and
      sorption of E2 in the liquid manure solution.

PMID- 21168959
TI  - Removal of residual pesticides in vegetables using ozone microbubbles.
AB  - The removal of fenitrothion (FT) pesticide residues from vegetables by immersion
      in ozone-microbubbled solution was demonstrated. FT-treated lettuce, cherry
      tomatoes, and strawberries were immersed in ozone-microbubbled, ozone
      millibubbled, and dechlorinated water. After that the percentage of residual FT
      in the vegetables was determined. Residual FT was efficiently removed from
      lettuce by immersing it in ozone-microbubbled solution containing more than 1.0
      ppm dissolved ozone, or continuously generated ozone-microbubbled solution
      containing 2.0 ppm dissolved ozone. Similarly, for cherry tomatoes and
      strawberries, the continuously generated ozone-microbubbled solution containing
      2.0 ppm dissolved ozone was highly effective. These results showed that ozone
      microbubbles effectively removed residual pesticides not only from leafy
      vegetables but also from fruity vegetables.

PMID- 21168960
TI  - Removal of rhodamine B using iron-pillared bentonite.
AB  - The iron-pillared bentonite (Fe-Ben) was prepared by ion-exchange using the
      natural bentonite (GZ-Ben) from Gaozhou, China, at room temperature without
      calcination. Both Fe-Ben and GZ-Ben were characterized by X-ray diffraction, N(2)
      adsorption and Fourier transform infrared spectroscopy. The results show that the
      d(001) value and surface area of the bentonite material increased after iron
      pillaring. Fe-Ben adsorbed much more Rhodamine B (RhB) than GZ-Ben, which can be
      ascribed to the special surface properties and large surface area of Fe-Ben. The
      optimum pH value for the adsorption of RhB on Fe-Ben is 5.0. The adsorption of
      RhB onto Fe-Ben can be well described by the pseudo-second-order kinetic model
      and the intraparticle diffusion kinetic model. The adsorption isotherm of RhB
      onto Fe-Ben matches well with the Langmuir model.

PMID- 21168961
TI  - Adsorptive removal of Cu(II) from aqueous solutions using collagen-tannin resin.
AB  - The collagen-tannin resin (CTR), as a novel adsorbent, was prepared via a
      reaction of collagen with black wattle tannin and aldehyde, and its adsorption
      properties to Cu(II) were systematically investigated, including pH effect,
      adsorption equilibrium, adsorption kinetics, and column adsorption. The
      adsorption capacity of Cu(II) on CTR was pH-dependent, and it increased with the
      increase of solution pH. The adsorption isotherms were well described by Langmuir
      isotherm model with correlating constant (R(2)) higher than 0.99. The adsorption
      capacity determined at 303 K was high up to 0.26 mmol/g, which was close to the
      value (0.266 mmol/g) estimated from Langmuir equation. The adsorption capacity
      was increased with the increase of temperature, and thermodynamic calculations
      suggested that the adsorption of Cu(II) on CTR is an endothermic process. The
      adsorption kinetics were well fitted by the pseudo-second-order rate model.
      Further column studies suggested that CTR was effective for the removal of Cu(II)
      from solutions, and more than 99% of Cu(II) was desorbed from column using 0.1
      mol/L HNO(3) solution. The CTR column can be reused to adsorb Cu(II) without any
      loss of adsorption capacity.

PMID- 21168962
TI  - Reduced graphene oxide-metal/metal oxide composites: facile synthesis and
      application in water purification.
AB  - This paper describes a versatile, and simple synthetic route for the preparation
      of a range of reduced graphene oxide (RGO)-metal/metal oxide composites and their
      application in water purification. The inherent reduction ability of RGO has been
      utilized to produce the composite structure from the respective precursor ions.
      Various spectroscopic and microscopic techniques were employed to characterize
      the as-synthesized composites. The data reveal that the RGO-composites are formed
      through a redox-like reaction between RGO and the metal precursor. RGO is
      progressively oxidized primarily to graphene oxide (GO) and the formed metal
      nanoparticles are anchored onto the carbon sheets. Metal ion scavenging
      applications of RGO-MnO(2) and RGO-Ag were demonstrated by taking Hg(II) as the
      model pollutant. RGO and the composites give a high distribution coefficient
      (K(d)), greater than 10 L g(-1) for Hg(II) uptake. The K(d) values for the
      composites are found to be about an order of magnitude higher compared to parent
      RGO and GO for this application. A methodology was developed to immobilize RGO
      composites on river sand (RS) using chitosan as the binder. The as-supported
      composites are found to be efficient adsorbent candidates for field application.

PMID- 21168955
TI  - Hepatitis B and C virus hepatocarcinogenesis: lessons learned and future
      challenges.
AB  - Worldwide, hepatocellular carcinoma (HCC) is one of the most common cancers. It
      is thought that 80% of hepatocellular carcinomas are linked to chronic infections
      with the hepatitis B (HBV) or hepatitis C (HCV) viruses. Chronic HBV and HCV
      infections can alter hepatocyte physiology in similar ways and may utilize
      similar mechanisms to influence the development of HCC. There has been
      significant progress towards understanding the molecular biology of HBV and HCV
      and identifying the cellular signal transduction pathways that are altered by HBV
      and HCV infections. Although the precise molecular mechanisms that link HBV and
      HCV infections to the development of HCC are not entirely understood, there is
      considerable evidence that both inflammatory responses to infections with these
      viruses, and associated destruction and regeneration of hepatocytes, as well as
      activities of HBV- or HCV-encoded proteins, contribute to hepatocyte
      transformation. In this review, we summarize progress in defining mechanisms that
      may link HBV and HCV infections to the development of HCC, discuss the challenges
      of directly defining the processes that underlie HBV- and HCV-associated HCC, and
      describe areas that remain to be explored.

PMID- 21168963
TI  - Adsorption of chromium(III), mercury(II) and lead(II) ions onto 4-aminoantipyrine
      immobilized bentonite.
AB  - In this work, the immobilization of 4-aminoantipyrine onto bentonite was carried
      out and it was then used to investigate the adsorption behavior of Cr(III),
      Hg(II) and Pb(II) ions from aqueous solutions. The separation and
      preconcentration conditions of analytes were investigated, including effects of
      pH, the shaking time, the sample flow rate and volume, the elution condition and
      the interfering ions. Under optimum pH value (pH 4.0), the maximum static
      adsorption capacity of the sorbent was found to be 38.8, 52.9 and 55.5 mg g(-1)
      for Cr(III), Hg(II) and Pb(II), respectively. 2.0 mL of 2% thiourea in 1.0 M HCl
      solution effectively eluted the adsorbed metal ions. The detection limit (3sigma)
      of this method defined by IUPAC was found to be 0.12, 0.09 and 0.23 ng mL(-1) for
      Cr(III), Hg(II) and Pb(II), respectively. The relative standard deviation (RSD)
      was lower 3.0% (n=8). The developed method has been validated by analyzing
      certified reference materials and successfully applied to the determination of
      trace Cr(III), Hg(II) and Pb(II) in water samples with satisfactory results.

PMID- 21168964
TI  - Performance evaluation for carbonation of steel-making slags in a slurry reactor.
AB  - CO(2) sequestration by the aqueous carbonation of steel-making slag under various
      operational conditions was investigated in this study. The effects of the
      operational conditions, including type of steel-making slag, reaction time,
      reaction temperature, and CO(2) flow rate, on the performance of the carbonation
      process were evaluated. The results indicated that the BOF slag had the highest
      carbonation conversion, approximately 72%, at a reaction time of 1h, an operating
      pressure of 101 kPa and a temperature of 60 degrees C due to its higher BET
      surface area of BOF slag compared to UF, FA, and BHC slags. The major factors
      affecting the carbonation conversion are reaction time and temperature. The
      reaction kinetics of the carbonation conversion can be expressed by the shrinking
      core model. The measurements of the carbonated material by the SEM and XRD
      instruments provide evidence indicating the suitability of using the shrinking
      core model in this investigation. Comparison of the results with other studies
      suggests that aqueous carbonation by slurry reactor is viable due to its higher
      mass transfer rate.

PMID- 21168965
TI  - Optimizing aeration rates for minimizing membrane fouling and its effect on
      sludge characteristics in a moving bed membrane bioreactor.
AB  - In MBR processes, sufficient aeration is necessary to maintain sustainable flux
      and to retard membrane fouling. Membrane permeability, sludge characteristics,
      nutrient removal and biomass growth at various air flow rates in the membrane and
      moving bed biofilm reactor (MBBR) compartments were studied in a pilot plant. The
      highest nitrogen and phosphorous removal rates were found at MBBR aeration rates
      of 151 and 85 L h(-1) and a specific aeration demand per membrane area (SAD(m))
      of 1.2 and 0.4 m(air)(3)  m(-2)  h(-1), respectively. A linear correlation was
      found between the amount of attached biofilm and the nutrient removal rate. The
      aeration rate in the MBBR compartment and SAD(m) significantly influenced the
      sludge characteristics and membrane permeability. The optimum combination of the
      aeration rate in the MBBR compartment and SAD(m) were 151 L h(-1) and 0.8-1.2
      m(air)(3) m(membrane)(-2)  h(-1), respectively.

PMID- 21168966
TI  - Kinetic and regeneration studies of photocatalytic magnetic separable beads for
      chromium (VI) reduction under sunlight.
AB  - Physical adsorption and photocatalytic reduction of Cr(VI) in magnetic separable
      beads were investigated. In order to elucidate the kinetics of photocatalytic
      process, operating parameters such as catalyst dosage and the initial
      concentration were examined in detail. It was observed that the reduction rate of
      Cr(VI) increased with an increase in the catalyst loading, as this translated
      into an increase in the number of available active sites. Critical scrutiny of
      the percentage of the initial reduction rate versus time at various initial
      concentration of Cr(VI) revealed that the rate of substrate conversion decreased
      as the initial concentration increased. The kinetic analysis of the
      photoreduction showed that the removal of Cr(VI) satisfactory obeyed the pseudo
      first-order kinetic according to the Langmuir-Hinshelwood (L-H) model and the
      absorption of Cr(VI) on the magnetic beads surfaces was the controlling step in
      the entire reduction process. Furthermore, desorption experiments by elution of
      the loaded gels with sodium hydroxide indicated that the magnetic photocatalyst
      beads could be reused without significant losses of their initial properties even
      after 3 adsorption-desorption cycles.

PMID- 21168967
TI  - A discussion on improving hydration activity of steel slag by altering its
      mineral compositions.
AB  - This study aims to investigate the ways to improve the cementitious properties of
      steel slag. The results show that the cementitious phase of steel slag is
      composed of silicate and aluminate, but the large particles of these phases make
      a very small contribution to the cementitious properties of steel slag. RO phase
      (CaO-FeO-MnO-MgO solid solution), Fe(3)O(4), C(2)F and f-CaO make no contribution
      to the cementitious properties of steel slag. A new kind of steel slag with more
      cementitious phase and less RO phase can be obtained by removing some large
      particles. This new steel slag possesses better cementitious properties than the
      original steel slag. The large particles can be used as fine aggregates for
      concrete. Adding regulating agent high in CaO and SiO(2) during manufacturing
      process of steel slag to increase the cementitious phase to inert phase ratio is
      another way to improve its cementitious properties. The regulating agent should
      be selected to adapt to the specific steel slag and the alkalinity should be
      increased as high as possible on the premise that the f-CaO content does not
      increase. The cooling rate should be enhanced to improve the hydration activity
      of the cementitious phase at the early ages and the grindability of steel slag.

PMID- 21168968
TI  - Electrochemical degradation of aromatic amines on BDD electrodes.
AB  - The electrochemical oxidation of four aromatic amines, with different substituent
      groups, 3-amino-4-hydroxy-5-nitrobenzenesulfonic acid (A1), 5-amino-2
      methoxybenzenesulfonic acid (A2), 2,4-dihydroxyaniline hydrochloride (A3) and
      benzene-1,4-diamine (A4), was performed using as anode a boron-doped diamond
      electrode, commercially available at Adamant Technologies. Tests were run at room
      temperature with model solutions of the different amines, with concentrations of
      200 ppm, using as electrolyte 0.035 M Na(2)SO(4) aqueous solutions, in a batch
      cell with recirculation, at different current densities (200 and 300 A m(-2)).
      The following analyses were performed with the samples collected during the
      assays: UV-Vis spectrophotometry, chemical oxygen demand (COD), total organic
      carbon (TOC), total Kjeldahl nitrogen, ammonia nitrogen, nitrates and HPLC.
      Results have shown a good electrodegradation of all the amines tested, with COD
      removals, after 6 h assays, higher than 90% and TOC removals between 60 and 80%.
      Combustion efficiency (eta(C)), which measures the tendency to convert organic
      carbon to CO(2), was also determined for all the amines, being
      eta(CA1)<eta(CA2)<eta(CA3)<eta(CA4)=0.99.

PMID- 21168969
TI  - A highly selective lead-sensitive electrode with solid contact based on ionic
      liquid.
AB  - A new polyvinylchloride membrane sensor for Pb(2+) with solid contact based on
      ionic liquid has been prepared. The electrode shows a Nernstian response for lead
      ions over a wide concentration range (1*10(-8) to 1*10(-1) mol L(-1)) and the
      slope of 29.8 mV/decade. The limit of detection is 4.3*10(-9) mol L(-1). It has a
      fast response time of 5-7 s and can be used for 4 months without any divergence
      in potential. The proposed sensor is not pH sensitive in the range 3.5-7.3 and
      shows a very good discriminating ability towards Pb(2+) ion in comparison with
      some alkali, alkaline earth, transition and heavy metal ions. It was successfully
      applied as an indicator electrode in potentiometric titration of lead ions with
      K(2)CrO(4) and for direct determination of Pb(2+) ions in real sample solution.

PMID- 21168970
TI  - Yttrium and lanthanides in human lung fluids, probing the exposure to atmospheric
      fallout.
AB  - Inhalation of airborne particles can produce crystallization of phosphatic
      microcrysts in intraaveolar areas of lungs, sometimes degenerating into pulmonary
      fibrosis. Results of this study indicate that these pathologies are induced by
      interactions between lung fluids and inhaled atmospheric dust in people exposed
      to volcanic dust ejected from Mount Etna in 2001. Here, the lung solid-liquid
      interaction is evaluated by the distribution of yttrium and lanthanides (YLn) in
      fluid bronchoalveolar lavages on selected individuals according the classical
      geochemical approaches. We found that shale-normalised patterns of yttrium and
      lanthanides have a 'V shaped' feature corresponding to the depletion of elements
      from Nd to Tb when compared to the variable enrichments of heavy lanthanides, Y,
      La and Ce. These features and concurrent thermodynamic simulations suggest that
      phosphate precipitation can occur in lungs due to interactions between volcanic
      particles and fluids. We propose that patterns of yttrium and lanthanides can
      represent a viable explanation of some pathology observed in patients after
      prolonged exposure to atmospheric fallout and are suitable to become a diagnostic
      parameter of chemical environmental stresses.

PMID- 21168971
TI  - Intrusive pain and worry about health in older men: the CHAMP study.
AB  - The role of anxiety in pain is less well understood than the role of depression.
      Based on recent conceptual thinking about worry and pain, we explored the
      relationship between pain status and worry about health and anxiety in 1217
      community-dwelling men aged 70 years or older who participated in the baseline
      phase of the Concord Health and Ageing in Men Project study, a large population
      based epidemiological study of healthy ageing based in Sydney, Australia. We
      hypothesised that worry about health would be associated with having persistent
      pain, and that the association would be stronger in the presence of co-existing
      pain-related interference with activities (intrusive pain). Of men in the study,
      12.5% had persistent and intrusive pain, 22.4% were worried about their health,
      and 6.3% had anxiety. We found a strong association between worry about health
      and pain that was both persistent and intrusive, and that remained after
      accounting for age, number of comorbidities, depression, self-rated health
      status, arthritis, and gait speed (adjusted odds ratio 2.9; 95% confidence
      interval 1.8-4.7), P<0.0001). The corresponding adjusted odds ratio for the
      association between anxiety and pain was 2.3 (95% confidence interval 1.0-4.8;
      P=0.0363). These findings suggest that at a population level, subthreshold
      anxiety and pain are strongly related, and worry about health occurs much more
      commonly than anxiety itself. To our knowledge, this is the first study to
      explore, specifically, the relationship between pain status and worry about
      health in older men. In older community-dwelling men, pain was robustly
      associated with worry about health, highlighting the potential importance of
      subthreshold anxiety-related psychological factors.

PMID- 21168972
TI  - Psychosocial approaches to pain management: an organizational framework.
AB  - Many different psychosocial treatments for pain have been described in the
      literature. All of these treatments have at least some evidence supporting their
      efficacy. However, each treatment is based on a theory or model that is most
      useful only for that particular intervention. An overarching model or framework
      that includes all of the factors hypothesized to play a role in the effects of
      these treatments would be useful for (1) understanding the similarities and
      differences between existing and future psychosocial pain treatments, (2) guiding
      the psychosocial evaluation of patients with chronic pain, and (3) giving
      clinicians greater flexibility for including psychosocial interventions that have
      proven efficacy, but that may not be explained by their preferred (but perhaps
      limited) model. This article proposes an initial version of such a framework,
      with the hope that it will increase our understanding of the role that
      psychosocial factors play in the experience of pain and its negative effects on
      functioning, and informs future research seeking to identify the common and
      specific factors associated with psychosocial pain treatments.

PMID- 21168973
TI  - Molecular characterization of Cryptosporidium spp. in pre-weaned dairy calves in
      the Czech Republic: absence of C. ryanae and management-associated distribution
      of C. andersoni, C. bovis and C. parvum subtypes.
AB  - A total of 750 faecal samples of dairy calves at up to 2 months of age kept in
      various housing systems were screened for Cryptosporidium spp. infection using
      the aniline-carbol-methyl violet staining method. DNA was extracted from
      Cryptosporidium positive samples and from 150 randomly selected microscopically
      negative samples. Nested PCR was performed to amplify the partial SSU rRNA gene
      of Cryptosporidium that was subsequently digested by SspI, VspI and MboII
      restriction enzymes to determine the present Cryptosporidium species and
      genotype. In addition, the samples characterized as Cryptosporidium parvum were
      subsequently analyzed at the GP60 gene to determine the distribution of zoonotic
      subtypes. Sequence analyses and RFLP identified C. parvum in 137, Cryptosporidium
      andersoni in 21 and Cryptosporidium bovis in 3 samples. Neither mixed infections
      nor Cryptosporidium ryanae was detected. Sequencing of the GP60 gene from C.
      parvum-positive samples revealed all five subtypes of family IIa (A15G2R1,
      A16G1R1, A22G1R1, A18G1R1, and A15G1R1). The obvious management-associated
      distribution of Cryptosporidium spp. was demonstrated. Direct contact with adult
      animals was found to be a risky factor for C. andersoni and C. bovis infection.
      IIaA15G2R1 and IIaA16G1R1 were detected as major subtypes, whereas only the
      IIaA16G1R1 subtype was found in animals kept in boxes. Three of the five detected
      subtypes were previously associated with human cryptosporidiosis, and moreover,
      the IIaA15G1R1 subtype, previously reported in humans only, was detected in
      calves for the first time.

PMID- 21168974
TI  - Tunicamycins, a class of nucleoside antibiotics similar to corynetoxins of the
      Rathayibacter toxicus, increase susceptibility of mice to Neospora caninum.
AB  - Neosporosis is the leading cause of abortion in cattle. Neospora caninum
      associated abortion may exhibit both endemic and epidemic patterns. It was
      reported that the epidemic outbreaks took place in the form of "abortion storms"
      and were not significantly correlated with seasonal changes or consumption of any
      particular feeds; and thus, the mechanisms by which the epidemic "abortion
      storms" are triggered remain unclear. Annual ryegrass toxicity (ARGT) is a severe
      or fatal neurological disorder of livestock of Australia and South Africa. This
      disorder is caused by the ingestion of several plant genera (Lolium, Polypogon,
      and Agrostis) colonized by a nematode (Anguina sp.) and a bacterium,
      Rathayibacter toxicus. Corynetoxins (CTs) produced by R. toxicus contaminate
      plants which are in turn ingested by sheep and cattle, causing severe or often
      fatal hepatocerebral disorders in affected animals. We hypothesize that N.
      caninum-associated fetal deaths and abortions in cattle may be potentiated by pre
      exposure of sublethal levels of CT-contaminated plants prior to N. caninum
      infection or reactivation of a latent infection. The exposure of sublethal CTs
      may not cause clinical diseases, but may increase susceptibility to pathogens
      such as N. caninum. Indeed, CT poisoning surviving pregnant sheep can have up to
      10% abortions. The present study investigated whether animals pre-exposed to
      tunicamycins (TMs), a functional substitute for CTs, had a lowered resistance to
      sublethal experimental infection by N. caninum tachyzoites in mice. The results
      showed that sublethal doses of TMs or N. caninum alone did not cause significant
      deaths. Sublethal doses of N. caninum induced high mortality in TM-treated mice
      in a dose dependent manner. When mice were treated with a low dose of TMs (5
      MUg/mouse), as few as 2.5 * 10(6) tachyzoites were needed to induce more than 30%
      of mortality which is equivalent to the mortality rate caused by 40 * 10(6)
      tachyzoites. Spleen cells of mice treated with TMs had reduced (p<0.05) Neospora
      antigen-induced interferon-gamma (IFN-g) production and Con A-stimulated
      proliferation. The results suggest that CT contaminated plants, when exposed to
      animals under natural conditions, may contribute to lowered host resistance and
      increased N. caninum-associated fetal morbidity and mortality in affected
      animals.

PMID- 21168975
TI  - Management of burn deformities using tissue expanders: a retrospective
      comparative analysis between tissue expansion in limb and non-limb sites.
AB  - The tissue expansion technique is in the armamentaria in reconstructive surgery.
      It provides donor skin that is an optimal match in terms of skin color, texture,
      sensation and hair-bearing characteristics. Literature shows its applications in
      all regions from the head to the feet. Tissue expansion in extremities, however,
      carries a high rate of complications. Fortunately, not every complication in
      tissue expansion means failure. OBJECTIVE: A retrospective comparative analysis
      between tissue expansion in limb and non-limb sites in burn deformities.
      MATERIALS AND METHODS: Sixty expanders in 53 patients were included. These
      constitute the experience of a single surgeon. Forty expanders (66.6%) were
      applied to non-limb sites and 20 expanders (33.3%) to limb sites. Indications of
      tissue expansion were burn alopecia, scarring and contracture. Complications and
      failures were recorded. RESULTS: Non-limb expanders had 10% rate of complications
      and 2.5% of failure. Limb expanders showed 30% complications and 15% failure.
      Statistical analysis showed that the difference was non-significant at this
      statistical power. CONCLUSION: The non-significant difference regarding
      complication and failure rates between limb and non-limb expanders in this study
      encourages the use of tissue expanders in extremities. Close follow-up of
      patients will prevent many expanders that develop complications from becoming
      failures.

PMID- 21168976
TI  - Evaluating the effects of a single copy of a mutation in the myostatin gene
      (c.*1232G>A) on carcass traits in crossbred lambs.
AB  - This study evaluated the effects of the ovine c.*1232G>A myostatin mutation (MM)
      on carcass traits in heterozygous crossbred lambs sired by Texel and Poll Dorset
      rams using ultrasound, CT scanning, carcass classification and VIA. In experiment
      1, MM was associated with increased loin depth (+2.8%) and area (+3.2%). MM
      carriers had significantly higher CT-estimated lean weight and proportion (2 to
      4%) and muscle to bone ratio (by ~3%), in both experiments, and muscle to fat
      ratio (28%) in experiment 2. Muscle areas in three cross-sectional CT scans, were
      higher (2 to 5%) in MM-carriers. In experiment 2, fat-related measurements were
      significantly lower in MM-carrier lambs but this was not seen in experiment 1. A
      significant increase in muscle density, indicative of lower intramuscular fat, in
      MM-carriers shows that meat quality characteristics need attention. Carrying MM
      significantly decreased carcass fat scores. VIA did not detect any significant MM
      effects.

PMID- 21168977
TI  - Colour stability of steaks from large beef cuts aged under vacuum or high oxygen
      modified atmosphere.
AB  - The aim was to investigate the effects of ageing large beef cuts, 10-cm-long
      longissimus dorsi (LD) and 4-cm-long semimembranosus (SM), on colour stability
      during subsequent storage of steaks in air for 5 days. Ageing solely in high
      oxygen modified atmosphere (MA, 80% O2 + 20% CO2) for 5 or 10 days or ageing in
      vacuum for 5 or 15 days followed by high oxygen MA for 5 or 10 days were compared
      with ageing in vacuum for 5, 15 and 25 days at 4  degrees C. Ageing system and
      ageing time influenced colour stability. For short ageing times, 5 to 10 days,
      large beef cuts could be aged in high oxygen MA without negative effect on colour
      stability compared with vacuum ageing. Longer ageing times, 15 to 25 days,
      decreased colour stability. Then vacuum ageing was preferable to ageing in vacuum
      for 5 or 15 days followed by high oxygen MA.

PMID- 21168978
TI  - Influence of salt content and processing time on sensory characteristics of
      cooked "lacon".
AB  - The influence of salt content and processing time on the sensory properties of
      cooked "lacon" were determined. "Lacon" is a traditional dry-cured and ripened
      meat product made in the north-west of Spain from the fore leg of the pig,
      following a similar process to that of dry-cured ham. Six batches of "lacon" were
      salted with different amounts of salt (LS (3 days of salting), MS (4 days of
      salting) and HS (5 days of salting)) and ripened during two times (56 and 84 days
      of dry-ripening). Cured odour in all batches studied, red colour and rancid odour
      in MS and HS batches, flavour intensity in MS batch and fat yellowness, rancid
      flavour and hardness in the HS batch were significantly different with respect to
      the time of processing. Appearance, odour, flavour and texture were not
      significantly affected by the salt content (P>0.05). However, the saltiness score
      showed significant differences with respect to the salt levels in all studied
      batches (56 and 84 days of process). The principal component analysis showed that
      physicochemical traits were the most important ones concerning the quality of dry
      cured "lacon" and offered a good separation of the mean samples according to the
      dry ripening days and salt level.

PMID- 21168980
TI  - Pisotriquetral arthrodesis for pisotriquetral instability: case report.
AB  - A 22-year-old professional downhill mountain bike rider developed increasing
      posttraumatic pisotriquetral instability. To preserve full function of the
      pisiform bone, we performed pisotriquetral arthrodesis using a Herbert screw. Ten
      months after the splint was removed, the patient was free of symptoms and
      returned to professional downhill mountain biking without limitations. This
      uncommon method seems to be a feasible treatment strategy and can be recommended
      in high-demand patients.

PMID- 21168979
TI  - Clinical outcomes following median to radial nerve transfers.
AB  - PURPOSE: To evaluate the clinical outcomes in patients with radial nerve palsy
      who underwent nerve transfers using redundant fascicles of median nerve
      (innervating the flexor digitorum superficialis and flexor carpi radialis
      muscles) to the posterior interosseous nerve and the nerve to the extensor carpi
      radialis brevis. METHODS: This was a retrospective review of the clinical records
      of 19 patients with radial nerve injuries who underwent nerve transfer procedures
      using the median nerve as a donor nerve. All patients were evaluated using the
      Medical Research Council (MRC) grading system. The mean age of patients was 41
      years (range, 17-78 y). All patients received at least 12 months of follow-up
      (range, 20.3 +/- 5.8 mo). Surgery was performed at a mean of 5.7 +/- 1.9 months
      postinjury. RESULTS: Postoperative functional evaluation was graded according to
      the following scale: grades MRC 0/5 to MRC 2/5 were considered poor outcomes,
      whereas an MRC grade of 3/5 was a fair result, 4/5 was a good result, and 4+/5
      was an excellent outcome. Postoperatively, all patients except one had good to
      excellent recovery of wrist extension. A total of 12 patients recovered good to
      excellent finger and thumb extension, 2 had fair recovery, and 5 had poor
      recovery. CONCLUSIONS: The radial nerve is commonly injured, causing severe
      morbidity in affected patients. The median nerve provides a reliable source of
      donor nerve fascicles for radial nerve reinnervation. The important nuances of
      both surgical technique and motor reeducation critical for the success of this
      transfer have been identified and are discussed. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 21168982
TI  - Adaptation of feline immunodeficiency virus subtype B strain TM2 to a feline
      astrocyte cell line (G355-5 cells).
AB  - Based on receptor usage during infection, feline immunodeficiency virus (FIV)
      isolates can be divided into two groups; those that require feline CD134 (fCD134)
      as a primary receptor in addition to CXCR4 to enter the cells, and those that
      require CXCR4 only. Most primary isolates, including strain TM2, belong to the
      former group and cannot infect a feline astrocyte cell line (G355-5 cells) due to
      a lack of fCD134 expression. In a previous study, we found that G355-5 cells
      transduced with fCD134 (termed G355-5/fOX40 cells) were susceptible to strain TM2
      and the inoculated cells became persistently infected. In this study, we examined
      the phenotype of the virus prepared from the persistently infected cells (termed
      strain TM2PI). Intriguingly, strain TM2PI replicated well in naive G355-5 cells
      and the inoculated G355-5 cells (termed G355-5/TM2PI cells) became persistently
      infected. The infection of TM2PI in G355-5 cells was inhibited by CXCR4
      antagonist AMD3100 and TM2PI infected other fCD134-negative, CXCR4-positive cell
      lines, FeTJ and 3201 cells. Four amino acid substitutions were found in the Env
      protein of the strain TM2PI when compared with that of the parental strain TM2.
      Among the substitutions, the Env amino acid position at 407 of TM2PI was
      substituted to lysine which has been known to be responsible for the FIV tropism
      for Crandell feline kidney cells. The strain TM2PI will be useful for studying
      the receptor switching mechanism and FIV pathogenesis in cats.

PMID- 21168981
TI  - Initiation and engagement in chronic disease management care for substance
      dependence.
AB  - BACKGROUND: Substance dependence treatment is often episodic and not well
      coordinated with healthcare for common comorbidities. Chronic disease/care
      management (CDM), longitudinal, patient-centered care delivered by
      multidisciplinary health professionals, may be well suited to treat substance
      dependence (SD). OBJECTIVE: To examine initiation and engagement with CDM care
      for SD located in a primary medical setting. METHODS: We prospectively studied
      substance dependent participants enrolled in a trial of CDM addiction care.
      Primary study outcomes, based upon Washington Circle performance measures, were
      14-day initiation of CDM care and 30-day engagement with CDM care. Factors
      associated with these outcomes were determined using multivariable logistic
      regression models. We also estimated the proportion of participants who
      eventually attended at least two visits and four visits by the end of the study
      (Kaplan-Meier method). RESULTS: Of 282 participants, approximately half of the
      cohort (45%, 95% Confidence Interval [CI] 39-51%) met criteria for 14-day
      initiation and 23% (95% CI 18-28%) for 30-day engagement with CDM care. Most
      participants attended two or more (81%, 95% CI 76-85%) and four or more CDM
      visits (62%, 95% CI 56-68%). Major depressive episode (AOR 2.60, 95% CI 1.39,
      4.87) was associated with higher odds of 14-day initiation; younger age, female
      sex, and higher alcohol addiction severity were associated with lower odds of 30
      day engagement with CDM care. CONCLUSION: People with SD appear to be willing to
      initiate and engage with CDM care in a primary medical care setting. CDM care has
      the potential to improve the quality of care for people with addictions.

PMID- 21168983
TI  - Primary infection protects pigs against re-infection with Lawsonia
      intracellularis in experimental challenge studies.
AB  - In two separate trials pigs were experimentally infected with Lawsonia
      intracellularis at 5-6 weeks of age followed by antibiotic treatment and
      resolution of the primary infection and then re-inoculated at 12-13 weeks of age.
      A treatment-control group of pigs received the primary infection and antibiotic
      treatment only, and served as control for the antibiotic treatment of the primary
      infection. A challenge-control group of pigs received the second inoculation dose
      only at 12-13 weeks of age to control infectivity of the challenge-dose and
      susceptibility of pigs to L. intracellularis at this age. Pigs were monitored for
      shedding of L. intracellularis in faeces by PCR, and for the development of
      antibodies and responses of acute phase proteins in serum. The presence of L.
      intracellularis antigen in the intestinal mucosa was examined in post mortem
      samples by immunohistochemistry. In both trials primary infected pigs were
      protected from infection after challenge inoculation as evidenced by absence of
      faecal shedding of L. intracellularis, lack of changes in acute phase protein
      concentrations after challenge and with low levels of bacterial antigen in the
      intestinal mucosa of re-inoculated pigs comparable to that of the treatment
      control pigs. In contrast, challenge-control pigs shed L. intracellularis in
      faeces, had L. intracellularis antigen extensively present within all layers of
      the intestinal mucosa and developed a significant acute phase protein response in
      serum after the experimental infection. The acute phase protein response to L.
      intracellularis infection was detected as an increased rise in the serum
      concentrations of C-reactive protein and haptoglobin from day-6 post infection,
      and increased serum concentrations of haptoglobin were generally seen 2-3 weeks
      after inoculation both at 5-6 and 12-13 weeks of age. In conclusion substantial
      protection against L. intracellularis infection was found in the re-inoculated
      pigs in contrast to the development of infection in age-matched control pigs. The
      acute phase protein responses reflected both the observed protection against L.
      intracellularis infection upon secondary challenge and that increased resistance
      to the infection develops with age.

PMID- 21168984
TI  - The effect of season on oocyte quality and developmental competence in Italian
      Mediterranean buffaloes (Bubalus bubalis).
AB  - At Italian latitudes, buffalo (Bubalus bubalis) is a seasonally polyestrous
      species, showing an improved reproductive efficiency when daylight decreases
      (autumn). The aim of the present study was to evaluate the influence of the
      season on buffalo oocyte recovery rate, on oocyte quality, assessed on
      morphological basis, and developmental competence after in vitro fertilization.
      For this purpose, buffalo ovaries were collected from a local abattoir and the
      oocytes obtained by aspirating the follicles were evaluated, classified and, if
      considered of good quality, devolved to the different procedures of IVEP. In
      general, no differences were found in terms of oocyte recovery per ovary among
      seasons, but interestingly, the percentage of small oocytes was higher (P<0.05)
      during spring and summer (0.9+/-0.1 and 0.9+/-0.2) compared to autumn and winter
      (0.3+/-0.1 and 0.2+/-0.1). Both cleavage and embryo rate increased during the
      period from October to December (71.7+/-3.1 and 26.5+/-2.1, respectively)
      compared to the period from April to June (58.0+/-2.4 and 18.8+/-1.6,
      respectively), thus reflecting the in vivo reproductive behavior. Nevertheless,
      it is worth emphasizing that transferrable embryos were produced in vitro, even
      during the unfavorable season, but with decreased efficiency. In conclusion,
      these results suggest to avoid the oocyte collection during spring when planning
      OPU trials in order to save resources and improve the benefits/costs ratio.

PMID- 21168985
TI  - Self-face recognition in children with autism spectrum disorders: a near-infrared
      spectroscopy study.
AB  - It is assumed that children with autism spectrum disorders (ASD) have
      specificities for self-face recognition, which is known to be a basic cognitive
      ability for social development. In the present study, we investigated
      neurological substrates and potentially influential factors for self-face
      recognition of ASD patients using near-infrared spectroscopy (NIRS). The subjects
      were 11 healthy adult men, 13 normally developing boys, and 10 boys with ASD.
      Their hemodynamic activities in the frontal area and their scanning strategies
      (eye-movement) were examined during self-face recognition. Other factors such as
      ASD severities and self-consciousness were also evaluated by parents and
      patients, respectively. Oxygenated hemoglobin levels were higher in the regions
      corresponding to the right inferior frontal gyrus than in those corresponding to
      the left inferior frontal gyrus. In two groups of children these activities
      reflected ASD severities, such that the more serious ASD characteristics
      corresponded with lower activity levels. Moreover, higher levels of public self
      consciousness intensified the activities, which were not influenced by the
      scanning strategies. These findings suggest that dysfunction in the right
      inferior frontal gyrus areas responsible for self-face recognition is one of the
      crucial neural substrates underlying ASD characteristics, which could potentially
      be used to evaluate psychological aspects such as public self-consciousness.

PMID- 21168986
TI  - The complete microspeciation of arginine and citrulline.
AB  - (1)H NMR-pH titrations of arginine, the most basic natural amino acid and
      citrulline, its neutral counterpart were carried out. Two other closely related
      auxiliary compounds were also studied. The 8 macroscopic protonation constants
      were determined. Combining the four datasets in a deductive method, all the 12
      microconstants of arginine, the 4 microconstants of citrulline and arginine amide
      were calculated. An error-propagation analysis and the pH-dependent distribution
      of the 8 arginine microspecies are provided.

PMID- 21168987
TI  - Capillary electrochromatography as a new tool to assess drug affinity for
      membrane phospholipids.
AB  - This work proposes a new capillary electrochromatography (CEC) method for
      determination of drug partition in membrane phospholipids. CEC experiments were
      carried out in a 100 MUm (ID) fused-silica capillary, partially packed with a
      chromatographic phospholipid stationary phase, so-called Immobilized Artificial
      Membrane, IAM.PC.DD2. The observed retention values were corrected by both the
      electro-osmotic and electrophoretic mobility values, measured by capillary
      electrophoresis (CE) experiments, assuming the values of the logarithms of
      "chromatographic" affinity factors, log k(CEC) as indexes of affinity for
      phospholipids. Analogously to biochromatography, all the values were determined
      with a totally aqueous mobile phase, or extrapolated to 100% aqueous buffer. The
      analytes were 16 structurally unrelated compounds, of basic, neutral, and acidic
      nature. To evaluate the effectiveness of CEC data to describe partition in
      phospholipids, log k(CEC) were related to both log P and log k(w)(IAM) values.
      log P are the lipophilicity values expressed as the logarithms of n-octanol/water
      partition coefficients and log k(w)(IAM) are the retention data measured by High
      Performance Liquid Chromatography (HPLC) on an IAM.PC.DD2 column, assumed as the
      reference values for phospholipid affinity. Phospholipid affinity scale by CEC
      related to that achieved by HPLC, but only if two different subclasses were
      considered separately, i.e. protonated and unprotonated analytes; indeed, all the
      compounds protonated at the experimental pH value (7.0) were retained stronger in
      CEC than in HPLC. This discrepancy may be due to the use of different buffers in
      CEC and HPLC since, to avoid the occurrence of a high current, the eluent in CEC
      experiments was of different composition and lower ionic strength than in HPLC.
      CEC analyses were faster and required lower amounts of both solvent and
      stationary phase than HPLC; moreover, with the exception of only three analytes,
      all analyses were performed with 100% aqueous eluents avoiding time-consuming and
      tedious extrapolation procedures.

PMID- 21168988
TI  - Electrodeless, accurate pH determination in highly basic media using a new set of
      (1)H NMR pH indicators.
AB  - A set of indicator molecules was selected and applied to elaborate an NMR-based
      pH determination method, free of glass electrode errors in highly basic media.
      Accurate measurement of pH values and protonation constants was achieved by a
      successive build-up of overlapping, increasingly high pH solutions, using a
      collection of 8 compounds of appropriately incremented basicities. In order to
      verify the method, acid-base properties were quantified for two compounds with
      very high basicities in conflicting reports: two pharmaceutically important
      biguanidine drugs, metformin and phenformin.

PMID- 21168989
TI  - Advanced analysis of nutraceuticals.
AB  - In this article, we present a review work on different nutraceuticals found in
      natural matrices together with the analytical techniques used to identify and/or
      quantify them with special emphasis in the period January 2005-May 2010. The work
      is distributed according to the different families of nutraceuticals (lipids,
      vitamins, proteins, glycosides, phenolic compounds, etc.) discussing the
      analytical techniques employed for their determination (separation,
      spectroscopic, hyphenated techniques, etc.). Information about the claimed health
      promoting effects of the different families of nutraceuticals is also provided
      together with data on the natural matrices in which they can be found (e.g.,
      fruits, vegetables, plants, microalgae, cereals, milk, etc.).

PMID- 21168990
TI  - Risk perception and risk communication.

PMID- 21168991
TI  - Prevalence and Axis I comorbidity of full and partial posttraumatic stress
      disorder in the United States: results from Wave 2 of the National Epidemiologic
      Survey on Alcohol and Related Conditions.
AB  - The present study used data from the Wave 2 National Epidemiologic Survey on
      Alcohol and Related Conditions (n = 34,653) to examine lifetime Axis I
      psychiatric comorbidity of posttraumatic stress disorder (PTSD) in a nationally
      representative sample of U.S. adults. Lifetime prevalences +/- standard errors of
      PTSD and partial PTSD were 6.4% +/- 0.18 and 6.6% +/- 0.18, respectively. Rates
      of PTSD and partial PTSD were higher among women (8.6% +/- 0.26 and 8.6% +/-
      0.26) than men (4.1% +/- 0.19 and 4.5% +/- 0.21). Respondents with both PTSD and
      partial PTSD most commonly reported unexpected death of someone close, serious
      illness or injury to someone close, and sexual assault as their worst stressful
      experiences. PTSD and partial PTSD were associated with elevated lifetime rates
      of mood, anxiety, and substance use disorders, and suicide attempts. Respondents
      with partial PTSD generally had intermediate odds of comorbid Axis I disorders
      and psychosocial impairment relative to trauma controls and full PTSD.

PMID- 21168992
TI  - Postural strategies in Prader-Willi and Down syndrome patients.
AB  - Patients affected by Down (DS) and Prader-Willi syndrome (PWS) are characterised
      by some common clinical and functional features including gait disorders and
      reduced postural control. The aim of our study was to quantitatively compare
      postural control in adult PWS and DS. We studied 12 PWS and 19 DS adult patients
      matched for age, height, weight and body mass index. They were instructed to
      maintain an upright standing position on a force platform for 30s with open eyes
      (OE) and we calculated the range of center of pressure (CoP) displacement in the
      A/P direction (RANGE(AP)) and in the M/L direction (RANGE(ML)) and the total CoP
      trajectory length during quiet stance (Sway Path, SP). The range of oscillations
      in PWS and DS in both AP and ML direction were higher than in controls. PWS and
      DS were statistically different for RANGE(AP), with PWS showing higher mean
      values. Our results confirm a reduced capacity of both PWS and DS in maintaining
      postural stability. This appears to be in some respect different in PWS and DS,
      with PWS showing poorer control in AP. DS and, particularly, PWS should be
      encouraged to undergo specific balance training and strengthening of the ankle
      muscles as part of a comprehensive rehabilitation program to enhance daily
      functioning and quality of life.

PMID- 21168993
TI  - Elevated peripheral blood mononuclear cell count is an independent predictor of
      left ventricular remodeling in patients with acute myocardial infarction.
AB  - OBJECTIVES: Peripheral blood mononuclear cells (PBMCs) increase after acute
      myocardial infarction (AMI) and infiltrate to the infarct region. However, its
      impact on left ventricular (LV) remodeling remains unclear. The purpose of the
      present study was to clarify whether elevated PBMC count contributed to LV
      remodeling in patients with AMI. SUBJECTS AND METHODS: A total of 131 patients
      with AMI were recruited. White blood cell (WBC), monocyte, and lymphocyte counts
      were measured at presentation and every 24h for five days after presentation. The
      correlation between PBMC count and LV remodeling was evaluated. LV remodeling was
      defined as an increase of LV end-diastolic volume index >= 10% at the 6-month
      follow-up left ventriculography. RESULTS: Forty-eight patients had LV remodeling.
      Peak WBC (p=0.008), peak monocyte (p=0.001), and peak PBMC (p<0.001) counts were
      significantly greater in patients with LV remodeling than those without
      remodeling. Multivariate analysis revealed the peak PBMC count >= 3600/mm(3) was
      an independent predictor of LV remodeling [relative risk (RR) 3.243, p=0.011].
      CONCLUSION: Increased PBMC count is significantly correlated with LV remodeling,
      thus suggesting that PBMCs play a pivotal role for the development of LV
      remodeling after AMI.

PMID- 21168994
TI  - Quality of monitoring for metabolic effects associated with second generation
      antipsychotics in patients with schizophrenia on public insurance.
AB  - Second generation antipsychotics (SGA) are associated with new onset diabetes,
      dyslipidemia and significant weight gain. Patients with schizophrenia are also at
      an increase risk of developing metabolic disorders, making routine metabolic
      monitoring important in patients with schizophrenia. The objective of our study
      was to identify glucose and lipid monitoring rates in Kansas Medicaid
      beneficiaries with schizophrenia who received long-term SGA therapy both before
      and after metabolic concerns of SGA had been introduced in the medical literature
      and after publication of metabolic monitoring guidelines from professional
      organizations in 2004. A retrospective cohort study was conducted using health
      care claims of Kansas Medicaid enrollees (age 18-64 years) with a diagnosis of
      schizophrenia and receiving long-term SGA. Proportions of these patients
      receiving annual blood glucose and serum lipid laboratory tests were calculated
      for two periods: 2002-2003 and 2005-2007. Bivariate and multivariate analyses
      were conducted to determine associations between demographic characteristics and
      monitoring outcomes. Among 2204 persons in the 2002 cohort, 23% received annual
      blood glucose monitoring and 10.1% received lipid monitoring. Among 1646 persons
      in the 2006 cohort, 75.3% received blood glucose monitoring and 52.5% received
      lipid monitoring. Our findings showed significant increases in blood glucose and
      lipid monitoring rates observed across a 4-year period in Kansas Medicaid
      enrollees with schizophrenia receiving SGA. The large rise in monitoring over
      time may be due to increase awareness of metabolic concerns by mental health care
      specialists, whom patients with schizophrenia are likely to receive their care
      from.

PMID- 21168995
TI  - New insight into genotype/phenotype correlations in ABCA12 mutations in harlequin
      ichthyosis.

PMID- 21168996
TI  - The 3'-UTR AACCins5874 in the stratum corneum chymotryptic enzyme gene
      (SCCE/KLK7), associated with atopic dermatitis; causes an increased mRNA
      expression without altering its stability.

PMID- 21168997
TI  - Pharmacodynamic profiling of intravenous antibiotics against prevalent Gram
      negative organisms across the globe: the PASSPORT Program-Asia-Pacific Region.
AB  - Due to escalating antimicrobial resistance amongst Gram-negative organisms, the
      choice of effective empirical antimicrobial regimens has become challenging.
      Monte Carlo simulations were conducted for conventional and prolonged infusion
      regimens of doripenem, imipenem and meropenem using pharmacokinetic data from
      adult patients with conserved renal function. Minimum inhibitory concentration
      data against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and
      Acinetobacter baumannii were incorporated from the COMPACT surveillance programme
      in the Asia-Pacific region of the world. The cumulative fraction of response
      (CFR) was determined for each regimen against each bacterial population. All
      simulated carbapenem regimens achieved an optimal CFR against E. coli and K.
      pneumoniae (94.5-100% CFR). Against P. aeruginosa, doripenem achieved 78.7-92.6%
      CFR, imipenem achieved 60.4-79.0% CFR and meropenem achieved 73.0-85.1% CFR. The
      only dosing regimen to achieve >= 90% CFR against P. aeruginosa was doripenem
      1000 mg and 2000 mg every 8 h (4-h infusion). Carbapenem CFRs against A.
      baumannii were much lower (29.2-54.4% CFR). CFRs for non-fermenting isolates were
      ca. 10% lower for isolates collected in the Intensive Care Unit. Carbapenem
      resistance amongst Enterobacteriaceae remains low in the Asia-Pacific region and
      thus standard carbapenem dosing regimens had a high likelihood of achieving
      pharmacodynamic exposures. However, larger doses combined with prolonged infusion
      will be required to increase the CFR for these carbapenems against resistant non
      fermenting Gram-negatives that are common in these countries. The safety and
      efficacy of these high dosing regimens will need to be confirmed in the clinical
      setting.

PMID- 21168998
TI  - Nortriptyline influences protein pathways involved in carbohydrate metabolism and
      actin-related processes in a rat gene-environment model of depression.
AB  - Although most available antidepressants increase monoaminergic neurotransmission,
      their therapeutic efficacy is likely mediated by longer-term molecular
      adaptations. To investigate the molecular changes induced by chronic
      antidepressant treatment we analysed proteomic changes in rat pre-frontal/frontal
      cortex and hippocampus after nortriptyline (NT) administration. A wide-scale
      analysis of protein expression was performed on the Flinders Sensitive Line
      (FSL), a genetically-selected rat model of depression, and the control Flinders
      Resistant Line (FRL). The effect of NT treatment was examined in a gene
      environment interaction model, applying maternal separation (MS) to both strains.
      In the forced swim test, FSL rats were significantly more immobile than FRL
      animals, whereas NT treatment reduced immobility time. MS alone did not modify
      immobility time, but it impaired the response to NT in the FSL strain. In the
      proteomic analysis, in FSL rats NT treatment chiefly modulated cytoskeleton
      proteins and carbohydrate metabolism. In the FRL strain, changes influenced
      protein polymerization and intracellular transport. After MS, NT treatment mainly
      affected proteins in nucleotide metabolism in FSL rats and synaptic transmission
      and neurite morphogenesis pathways in FRL rats. When the effects of NT treatment
      and MS were compared between strains, carbohydrate metabolic pathways were
      predominantly modulated.

PMID- 21168999
TI  - Radiotherapy for pain.
AB  - Radiotherapy has been proven to be an effective treatment for the palliation of
      symptomatic bone metastases. Despite its widespread use and long history, there
      remains considerable debate over whether a single 8 Gy fraction or multiple
      fraction schemes are more effective at alleviating bone pain. Recent meta
      analyses have shown equal efficacy between the different treatment regimens. One
      of the reasons supporting multiple fraction use is a lower re-irradiation rate.
      Recent research has explored many issues associated with retreatment, including
      timing, appropriate patient selection and concerns of toxicities. However, there
      are notable side-effects due to radiotherapy, perhaps one of the most significant
      being 'pain flare', which is a temporary increase in bone pain immediately after
      treatment. It has a reported incidence of up to 44% in patients. Despite possible
      side-effects like 'pain flare', radiotherapy can improve pain and also quality of
      life for patients. One of the quality of life tools that has become useful for
      assessing the effectiveness of palliative radiotherapy on physical, psychosocial
      and functional issues is the EORTC-QLQ-BM22. In addition to tracking quality of
      life changes in patients, analysing symptom clusters can be used to better
      understand the symptomatology of advanced cancer, and how radiotherapy can affect
      pain and other symptoms that cancer patients commonly experience.

PMID- 21169000
TI  - A morphometric study concerning the branching points of the main arteries in
      humans: relationships and correlations.
AB  - An adequate quantity of data on the branching points and important arterial
      segments of the main arteries in humans is missing. Moreover, a suitable data
      collection and thereby observed correlations might provide some important clues
      relating to angiogenesis issues. Thus, we chose to examine in sixty-two embalmed
      human cadavers of Hellenic origin: The level and angles of the branching points
      did not differ substantially from similar data, mentioned in the literature. Our
      results revealed that symmetry exists between the limbs and the aortic length and
      the branching positions of the abdominal aorta. The aortic length is negatively
      related to the length of both common iliac arteries. The lengths of the celiac
      and the brachiocephalic artery (correlated weakly with one another) presented
      fewer correlations, while the segment between the inferior mesenteric and the
      celiac artery was correlated with other segments from different locations mainly
      on the right side. This last distance, the aortic length, the distance between
      the celiac and inferior mesenteric arteries, the length of both common femoral
      arteries differed significantly according to gender, independently of body length
      and height. Our data support the view that the final position and length of the
      arteries might be due to the location of the corresponding viscera during
      angiogenesis, to the body length and height and to some (hypothetical) elongation
      angiogenetic factors.

PMID- 21169001
TI  - 'Dressed for success' C-type lectin receptors for the delivery of glyco-vaccines
      to dendritic cells.
AB  - Current strategies in immunotherapy for the treatment of tumors or autoimmunity
      focus on direct in vivo targeting of antigens to dendritic cells (DC), as these
      cells are the key regulators of immune responses. Multiple DC subsets can be
      distinguished in both humans and mice, based on phenotype and location. Moreover,
      recent data show that these subsets have distinct functions. All these features
      have implications for the design of DC-targeting vaccines. In this review we
      integrate recent knowledge on the different DC subsets in human and mice and how
      DC-expressed C-type lectin receptors (CLR) can be exploited for the induction of
      either antigen-specific immunity or tolerance.

PMID- 21169002
TI  - Cysteinyl leukotriene antagonism inhibits bronchoconstriction in response to
      hypertonic saline inhalation in asthma.
AB  - BACKGROUND: In asthma, cysteinyl leukotrienes (CysLTs) play varying roles in the
      bronchomotor response to multiple provocative stimuli. The contribution of CysLTs
      on the airway's response to hypertonic saline (HS) inhalation in asthma is
      unknown. Whether polymorphisms in the leukotriene biosynthetic pathway affect the
      contribution of CysLTs to this response is also unknown. METHODS: In a
      prospective, randomized, double-blind, placebo-controlled cross-over study, mild
      and moderate asymptomatic asthmatics underwent inhaled 3% HS challenge by
      doubling the duration of nebulization (0.5, 1, 2, 4, and 8 min) 2 h after one
      dose of montelukast (a CysLT receptor 1 [CysLTR1] antagonist) or placebo, and
      after three-week courses. We examined the effect of the leukotriene C(4) synthase
      (LTC(4)S) polymorphism (A-444C) on the efficacy of montelukast against HS
      inhalation in an exploratory manner. RESULTS: In 37 subjects, 2 h after
      administration of montelukast, the mean provocative dose of HS required to cause
      a 20% drop in FEV(1) (HS-PD(20)) increased by 59% (9.17 ml after placebo vs.
      14.55 ml after montelukast, p=0.0154). Three weeks of cysLTR1 antagonism
      increased the HS-PD(20) by 84% (10.97 vs. 20.21 ml, p=0.0002). Three weeks of
      CysLTR1 antagonism appeared to produce greater effects on blocking bronchial
      hyper-responsiveness (2 h vs. three-week HS-PD(20) values 14.55 vs. 20.21 ml
      respectively, p=0.0898). We did not observe an effect of the LTC(4)S polymorphism
      on the response to CysLTR1 antagonism in this cohort. CONCLUSIONS: A significant
      proportion of HS-induced bronchoconstriction is mediated by release of
      leukotrienes as evidenced by substantial acute inhibition with a CysLTR1
      antagonist. There was a trend toward greater inhibition of bronchial
      responsiveness with three weeks of therapy as opposed to acute CysLTR1
      antagonism. Clinicaltrials.gov registration number NCT00116324.

PMID- 21169004
TI  - Proteostenosis and plasma cell pathophysiology.
AB  - Plasma cells differentiate from B lymphocytes to sustain antibody production. As
      professional secretors, they allow dissecting proteostasis in the exocytic
      compartment, the stresses that protein production entails and their possible
      roles in signaling. Most plasma cells are short-lived to limit antibody
      responses. After a few days of intense immunoglobulin production, they undergo
      apoptosis, offering a unique model of cellular senescence. Recent observations
      reveal that proteotoxic stresses physiologically contribute to regulate their
      biogenesis, function and lifespan, explaining partly the sensitivity of multiple
      myeloma cells to proteasome inhibitors. This essay summarizes these plasma cell
      lessons, and their general implications for the regulation of proteostasis, cell
      senescence and cancer therapeutics.

PMID- 21169003
TI  - Transcription and recombination factories: common features?
AB  - There is now substantial evidence that the eukaryotic nucleus consists of highly
      organized structures. Among such structures are transcription factories that
      consist of an ensemble of genes recruited by the RNA polymerase machinery. Here
      we suggest that antigen receptor variable regions are similarly organized.
      Specifically, we propose that the immunoglobulin heavy chain locus variable gene
      segments are anchored to the base of rosettes, wrapping around a cavity that
      contains the recombination machinery. We suggest that the folding of the
      chromatin fiber into rosettes underpins a crucial mechanism by which antigen
      receptor diversity is generated.

PMID- 21169005
TI  - Improving the aeration of critical fine-grained landfill top cover material by
      vegetation to increase the microbial methane oxidation efficiency.
AB  - The natural methane oxidation potential of methanotrophic bacteria in landfill
      top covers is a sustainable and inexpensive method to reduce methane emissions to
      the atmosphere. Basically, the activity of methanotrophic bacteria is limited by
      the availability of oxygen in the soil. A column study was carried out to
      determine whether and to what extent vegetation can improve soil aeration and
      maintain the methane oxidation process. Tested soils were clayey silt and mature
      compost. The first soil is critical in light of surface crusting due to vertical
      erosion of an integral part of fine-grained material, blocking pores required for
      the gas exchange. The second soil, mature compost, is known for its good methane
      oxidation characteristics, due to high air-filled porosity, favorable water
      retention capacity and high nutrient supply. The assortment of plants consisted
      of a grass mixture, Canadian goldenrod and a mixture of leguminous plants. The
      compost offered an excellent methane oxidation potential of 100% up to a CH(4)
      input of 5.6l CH(4)m(-2)h(-1). Whereas the oxidation potential was strongly
      diminished in the bare control column filled with clayey silt even at low CH(4)
      loads. By contrast the planted clayey silt showed an increased methane oxidation
      potential compared to the bare column. The spreading root system forms secondary
      macro-pores, and hence amplifies the air diffusivity and sustain the oxygen
      supply to the methanotrophic bacteria. Water is produced during methane
      oxidation, causing leachate. Vegetation reduces the leachate by
      evapotranspiration. Furthermore, leguminous plants support the enrichment of soil
      with nitrogen compounds and thus improving the methane oxidation process. In
      conclusion, vegetation is relevant for the increase of oxygen diffusion into the
      soil and subsequently enhances effective methane oxidation in landfill cover
      soils.

PMID- 21169006
TI  - Modelling of environmental impacts from biological treatment of organic municipal
      waste in EASEWASTE.
AB  - The waste-LCA model EASEWASTE quantifies potential environmental effects from
      biological treatment of organic waste, based on mass and energy flows, emissions
      to air, water, soil and groundwater as well as effects from upstream and
      downstream processes. Default technologies for composting, anaerobic digestion
      and combinations hereof are available in the model, but the user can change all
      key parameters in the biological treatment module so that specific local plants
      and processes can be modelled. EASEWASTE is one of the newest waste LCA models
      and the biological treatment module was built partly on features of earlier waste
      LCA models, but offers additional facilities, more flexibility, transparency and
      user-friendliness. The paper presents the main features of the module and
      provides some examples illustrating the capability of the model in
      environmentally assessing and discriminating the environmental performance of
      alternative biological treatment technologies in relation to their mass flows,
      energy consumption, gaseous emissions, biogas recovery and compost/digestate
      utilization.

PMID- 21169007
TI  - Using a contingent valuation approach for improved solid waste management
      facility: evidence from Kuala Lumpur, Malaysia.
AB  - This study employed contingent valuation method to estimate the willingness to
      pay (WTP) of the households to improve the waste collection system in Kuala
      Lumpur, Malaysia. The objective of this study is to evaluate how household WTP
      changes when recycling and waste separation at source is made mandatory. The
      methodology consisted of asking people directly about their WTP for an additional
      waste collection service charge to cover the costs of a new waste management
      project. The new waste management project consisted of two versions: version A
      (recycling and waste separation is mandatory) and version B (recycling and waste
      separation is not mandatory). The households declined their WTP for version A
      when they were asked to separate the waste at source although all the facilities
      would be given to them for waste separation. The result of this study indicates
      that the households were not conscious about the benefits of recycling and waste
      separation. Concerted efforts should be taken to raise environmental
      consciousness of the households through education and more publicity regarding
      waste separation, reducing and recycling.

PMID- 21169008
TI  - Trend of the research on construction and demolition waste management.
AB  - Research interests in addressing construction and demolition (C&D) waste
      management issues have resulted in a large amount of publications during the last
      decade. This study demonstrates that there is no systematic examination on the
      research development in literature in the discipline of C&D waste management.
      This study presents the latest research trend in the discipline through analyzing
      the publications from 2000 to 2009 in eight major international journals. The
      analysis is conducted on the number of papers published annually, main authors'
      contributions, research methods and data analysis methods adopted, and research
      topics covered. The results exhibit an increasing research interest in C&D waste
      management in recent years. Researchers from developed economies have contributed
      significantly to the development of the research in the discipline. Some
      developing countries such as Malaysia and China have also been making good
      efforts in promoting C&D waste management research. The findings from this study
      also indicate that survey and case study are major methods for data collection,
      and the data are mostly processed through descriptive analysis. It is anticipated
      that more future studies on C&D waste management will be led by researchers from
      developing economies, where construction works will remain their major economic
      activities. On the other hand, more sophisticated modeling and simulating
      techniques have been used effectively in a number of studies on C&D waste
      management research, and this is considered a major methodology for future
      research in the discipline. C&D waste management will continue to be a hot
      research topic in the future, in particularly, the importance of human factors in
      C&D waste management has emerged as a new challenging topic.

PMID- 21169009
TI  - Immunochromatographic strip test for detection of genus Cronobacter.
AB  - Members of the genus Cronobacter are opportunistic pathogens formerly known as
      Enterobacter sakazakii, which induce severe meningitis and sepsis in neonates and
      infants, with a high fatality rate. In this work, a simple and rapid
      immunochromatographic strip test for the detection of this pathogen was
      developed. Following the shortened bacteria cultivation and isolation of DNA, a
      specific gene sequence targeting 16S rRNA from Cronobacter spp. was amplified by
      PCR using 5'-end labelled specific primers. The PCR product, amplicon labelled
      with digoxigenin on one side and biotin on the other side, was directly added to
      the immunochromatographic strip test, composed of nitrocellulose membrane with
      bound antibody against digoxigenin in the test line. The visualization was
      mediated by colloidal carbon conjugated to neutravidin, and the appearance of
      grey/black line was indicative of the presence of specific amplicon. Colour
      intensity of the test line in pathogen-positive assay was visually
      distinguishable from that of negative sample within 10 min. The visual detection
      limit of PCR product was 8 ng. The specificity of the developed method was
      confirmed by standard microbiological techniques. Whole detection procedure with
      the incorporated immunostrip was applied to analysis of infant formulae samples,
      contaminated with less than 10 cells of Cronobacter spp. per 10 g. The results
      from immunochromatographic test indicated the absolute agreement with those from
      standard microbiological methods. Moreover, the developed procedure considerably
      reduced the total analysis time to 16 h whereas the reference microbiological
      method needs 6-7 days.

PMID- 21169010
TI  - An innovative miniature microbial fuel cell fabricated using photolithography.
AB  - Recently microbial fuel cells (MFCs) have attracted increasing interests in both
      environmental and energy fields. Among the various MFC configurations, miniature
      microbial fuel cell (mini-MFC) has a great potential for the application in
      medical, communication and other areas because of its miniature volume and high
      output power density. In this work, a 25-MUL single-chamber mini-MFC was
      fabricated using the photolithography technique. The plate-shaped gold anodic
      electrode in the mini-MFC showed a higher electrochemical activity than the
      stripe-shaped one. A biofilm of Shewanella oneidensis MR-1 was formed on the
      surface of gold electrode in this micro-liter-scale MFCs. As a result, a maximum
      power density of 29 mW/m(2) and a maximum current density of 2148 mA/m(2) were
      achieved by this single-chamber mini-MFC.

PMID- 21169011
TI  - Lumbar ultrasound: useful gadget or time-consuming gimmick?
AB  - Despite widespread enthusiasm for using lumbar ultrasound in obstetrics, there
      are some who believe it is expensive and time-consuming, with undetermined risks
      and uncertain benefits. For decades, anesthesiologists have striven to perfect
      the identification and cannulation of the epidural space using skills learned
      during training and early clinical practice. These skills include knowledge of
      the relevant anatomy and detection of subtle tactile clues that aid successful
      placement of an epidural catheter. Indeed, obstetric anesthesiologists have
      managed to do this with great success without using imaging techniques. There is
      a long learning curve associated with lumbar ultrasound and it is unclear from
      the literature if the success rates associated with its use are superior to
      clinical skill alone. Is it only a matter of time before regulators insist that
      lumbar ultrasound is used before inserting an epidural? Indeed, this has already
      happened for central vein catheters. The United States spent $2.2 trillion on
      health care in 2007, nearly twice the average of other developed nations. If
      rapid health cost growth persists, one out of every four dollars in the US
      national economy will be tied up in the health system by 2025. Do obstetric
      anesthesiologists want to add to these costs by using unnecessary and expensive
      equipment? Although many feel that diagnostic ultrasound in obstetrics is safe,
      some argue that we have yet to perform an appropriate risk analysis for lumbar
      ultrasound during pregnancy. The issue of ultrasound bio-safety needs to be
      considered before we all jump on the ultrasound bandwagon.

PMID- 21169012
TI  - Anaesthesia for caesarean section in a patient with Budd-Chiari syndrome and
      hepatopulmonary syndrome post liver transplantation.
AB  - Hepatopulmonary syndrome is characterised by hypoxaemia and intrapulmonary
      shunting in the presence of portal hypertension. It is uncommon in the obstetric
      population but may occur in patients with Budd-Chiari syndrome in the absence of
      severe liver dysfunction. We discuss the management of a primigravida with Budd
      Chiari syndrome and persistent hepatopulmonary syndrome post liver
      transplantation. A literature review revealed only one report of a successful
      pregnancy in association with hepatopulmonary syndrome. We discuss its
      recognition in patients with liver disease and anaesthetic considerations in its
      presence.

PMID- 21169013
TI  - Changes in microbial and nutrient composition associated with rumen content
      compost incubation.
AB  - Physico-chemical and microbiological investigations were carried out on rumen
      content material composted for nine months, fresh vermicasts (obtained after
      passing the same compost through the guts of a mixture of three species of
      earthworms: Eisenia fetida, Lumbricus rubellus and Perionyx excavates) and
      microbially enhanced extracts derived from rumen compost, vermicast and vermicast
      leachate incubated for up to 48 h. Compared to composted rumen contents,
      vermicast was only improved in terms of microbial biomass C, while vermicast
      leached extract was significantly higher in NH(4)(+)-N,PO(4)(-)-P, humic acid,
      bacterial counts and total microbial activity compared to rumen compost extract.
      Although no difference between treatments was observed in genetic diversity as
      indicated by DGGE analysis, community level functional diversity of vermicast
      leached extract (BiologTM) was higher than that of composted rumen contents,
      vermicast and rumen compost extract indicating an enhancement of microbial
      activity rather than diversity due to liquid incubation.

PMID- 21169014
TI  - Construction and characterization of different fusion proteins between cellulases
      and beta-glucosidase to improve glucose production and thermostability.
AB  - A beta-glucosidase from Clostridium cellulovorans (CcBG) was fused with one of
      three different types of cellulases from Clostridium thermocellum, including a
      cellulosomal endoglucanase CelD (CtCD), a cellulosomal exoglucanase CBHA (CtCA)
      and a non-cellulosomal endoglucanase Cel9I (CtC9I). Six bifunctional enzymes were
      constructed with either beta-glucosidase or cellulase in the upstream. CtCD-CcBG
      showed the favorable specific activities on phosphoric acid swollen cellulose
      (PASC), an amorphous cellulose, with more glucose production (2 folds) and less
      cellobiose accumulation (3 folds) when compared with mixture of the single
      enzymes. Moreover, CtCD-CcBG had significantly improved thermal stability with a
      melting temperature (T(m)) of 10.9 degrees C higher than that of CcBG (54.5
      degrees C) based on the CD unfolding experiments. This bifunctional enzyme is
      thus useful in industrial application to convert cellulose to glucose.

PMID- 21169015
TI  - Efficient production of butyric acid from Jerusalem artichoke by immobilized
      Clostridium tyrobutyricum in a fibrous-bed bioreactor.
AB  - Butyric acid is an important specialty chemical with wide industrial
      applications. The feasible large-scale fermentation for the economical production
      of butyric acid requires low-cost substrate and efficient process. In the present
      study, butyric acid production by immobilized Clostridium tyrobutyricum was
      successfully performed in a fibrous-bed bioreactor using Jerusalem artichoke as
      the substrate. Repeated-batch fermentation was carried out to produce butyric
      acid with a high butyrate yield (0.44 g/g), high productivity (2.75 g/L/h) and a
      butyrate concentration of 27.5 g/L. Furthermore, fed-batch fermentation using
      sulfuric acid pretreated Jerusalem artichoke hydrolysate resulted in a high
      butyric acid concentration of 60.4 g/L, with the yield of 0.38 g/g and the
      selectivity of ~ 85.1 (85.1g butyric acid/g acetic acid). Thus, the production of
      butyric acid from Jerusalem artichoke on a commercial scale could be achieved
      based on the system developed in this work.

PMID- 21169016
TI  - A novel screening model for the molecular drug for diabetes and obesity based on
      tyrosine phosphatase Shp2.
AB  - Tyrosine phosphatase Src-homology phosphotyrosyl phosphatase 2 (Shp2) was
      identified as a potential molecular target for therapeutic treatment of diabetes
      and obesity. However, there is still no systematic research on the enhancers for
      the Shp2 enzyme. The present study established a novel powerful model for the
      high-throughput screening of Shp2 enhancers and successfully identified a new
      specific Shp2 enhancer, oleanolic acid, from Chinese herbs.

PMID- 21169017
TI  - Discovery of novel class 1 phosphatidylinositide 3-kinases (PI3K) fragment
      inhibitors through structure-based virtual screening.
AB  - The discovery of ligand efficient and lipophilicity efficient fragment inhibitors
      of class 1 phosphatidylinositide 3-kinases (PI3K) is reported. A fragment version
      of the AstraZeneca compound bank was docked to a homology model of the PI3K
      p110beta isoform. Interaction-based scoring of the predicted binding poses served
      to further prioritise the virtual fragment hits. Experimental screening confirmed
      potency for a total of 18 fragment inhibitors, belonging to five different
      structural classes.

PMID- 21169018
TI  - White matter abnormalities and neurocognitive correlates in children and
      adolescents with myotonic dystrophy type 1: a diffusion tensor imaging study.
AB  - Diffusion tensor imaging was used to evaluate cerebral white matter in eight
      patients (ages 10-17), with myotonic dystrophy type 1 (3 congenital-onset, 5
      juvenile-onset) compared to eight controls matched for age and sex. Four regions
      of interest were examined: inferior frontal, superior frontal, supracallosal, and
      occipital. The myotonic dystrophy group showed white matter abnormalities
      compared to controls in all regions. All indices of white matter integrity were
      abnormal: fractional anisotropy, mean diffusivity, axial diffusivity, and radial
      diffusivity. With no evidence of regional variation, correlations between whole
      cerebrum white matter fractional anisotropy and neurocognitive functioning were
      examined in the patients. Strong correlations were observed between whole
      cerebrum fractional anisotropy and full-scale intelligence and a measure of
      executive functioning. Results indicate that significant white matter abnormality
      is characteristic of young patients with myotonic dystrophy type 1 and that the
      white matter abnormality seen with neuroimaging has implications for cognitive
      functioning.

PMID- 21169019
TI  - Dysregulation and cellular mislocalization of specific miRNAs in myotonic
      dystrophy type 1.
AB  - Myotonic Dystrophy Type-1 (DM1) is caused by the expansion of a CTG repeat with a
      peculiar pattern of multisystemic involvement affecting skeletal muscles, the
      heart, the eye, the central nervous system and the endocrine system. Since
      microRNA expression is disrupted in several myopathies, the expression of 24
      candidate microRNAs was analyzed in skeletal muscle biopsies of 15 DM1 patients.
      Controls were constituted by biopsies without overt pathological features derived
      from 14 subjects with suspected neuromuscular disorder of undetermined nature. We
      found that miR-1 and miR-335 were up-regulated, whereas miR-29b and c, and miR-33
      were down-regulated in DM1 biopsies compared to controls. We also found that the
      cellular distribution of muscle specific miR-1, miR-133b and miR-206 was severely
      altered in DM1 skeletal muscles. MicroRNA dysregulation was likely functionally
      relevant, since it impacted on the expression of the predicted miR-1, and miR-29
      targets. The observed miRNA dysregulations and myslocalizations may contribute to
      DM1 pathogenetic mechanisms.

PMID- 21169020
TI  - Exploring the validity of the bispectral index, the Critical-Care Pain
      Observation Tool and vital signs for the detection of pain in sedated and
      mechanically ventilated critically ill adults: a pilot study.
AB  - This pilot study aimed to explore the validity of the bispectral (BIS) index, the
      Critical-Care Pain Observation Tool (CPOT) score, and vital signs (mean arterial
      pressure, heart rate) during rest and painful procedures in sedated and
      mechanically ventilated ICU adults. A convenience sample of nine patients with
      various diagnoses participated in this observational repeated measures study.
      Patients were observed during 2 minute periods at rest (baseline), and during
      procedures known to be painful: turning and endotracheal suctioning. Both the BIS
      index and the CPOT score were found to increase when patients were exposed to
      procedures compared with rest, and were found to be more sensitive to procedures
      compared with vital signs. Indeed, vital signs remained quite stable during
      procedures in this sample. Results from this study support the recommendation
      that behavioural indicators (i.e. in this case, the use of a behavioural pain
      scale called the CPOT) be used for the detection of pain in nonverbal ICU
      patients. However, in some situations (e.g. deep sedation, use of blocking
      agents), behavioural indicators may no longer be observable, and all that is left
      are physiologic signs. The BIS seems to be an interesting technique and further
      research is required in order to establish if it could be used to guide
      clinicians for the detection of pain in this vulnerable population.

PMID- 21169021
TI  - Muscle strength and walking ability in diplegic cerebral palsy: implications for
      assessment and management.
AB  - Muscle weakness is a recognised problem in children with Cerebral Palsy (CP).
      Changes in the understanding of motor control, and progress in the treatment of
      spasticity, have led to a greater appreciation that spastic muscles are also
      weak. In recent years weakness has been identified in isolated muscle groups, but
      studies quantifying the degree and distribution of weakness in multiple muscles
      remain limited. This study evaluated isometric lower limb muscle strength in 50
      ambulant children with CP/Spastic Diplegia (mean age 11 years 7 months) at GMFCS
      levels I (n=14), II (n=26) and III (n=10). Muscle strength was compared with 15
      control children (mean age 11 years 1 month) using the same protocol. Six muscle
      groups in both lower limbs were measured using a digital dynamometer. All lower
      limb muscles were significantly weaker in the CP children than in healthy
      children (p<0.05) except for the hip extensors. Muscle strength ranged from 43%
      to 90% of control values depending on the muscle group, with the knee extensors
      measured at 30 degrees  being the relatively weakest group. There was a
      significant difference in strength between GMFCS levels in 4/6 muscle groups with
      a progressive reduction in strength in all muscle groups with increasing walking
      difficulty from GMFCS levels I to III. The greatest difference in strength
      between independent walkers and those dependent on walking aids was in the hip
      abductors and knee extensors at 30 degrees , which are key muscle groups in
      sagittal and coronal plane walking stability. This has implications in targetting
      strength training to maximise functional outcomes.

PMID- 21169022
TI  - Predicted knee kinematics and kinetics during functional activities using motion
      capture and musculoskeletal modelling in healthy older people.
AB  - Knowledge of joint forces and moments is essential for comparisons between
      healthy people and those with pathological conditions, with observed changes at
      joints providing basis for a particular intervention. Currently the literature
      analysing both kinematics and kinetics at the knee has been limited to small
      samples, typically of young subjects or those who have undergone joint
      arthroplasty. In this study, we examined tibiofemoral joint (TFJ) kinematics and
      kinetics during gait, sit-stand-sit, and step-descent in 20 healthy older
      subjects (aged 53-79 years) using motion capture data and inverse dynamic
      musculoskeletal models. Mean peak distal-proximal force in the TFJ were 3.1, 1.6,
      and 3.5 times body weight (N/BW) for gait, sit-stand, and step-descent
      respectively. There were also significant posterior-anterior forces, with sit
      stand activity peaking at 1.6 N/BW. Moments about the TFJ peaked at a mean of
      0.07 Nm/BW during the sit-stand activity. One of the most important findings of
      this study was variability found across the subjects, who spanned a wide age
      range, showing large standard deviations in all of the activities for both
      kinematics and kinetics. These data have provided an initial prediction for
      assessing kinematics and kinetics in the older population. Larger studies are
      needed to refine the database, in particular to reduce the variability in the
      results by studying sub-populations, to enable more robust comparisons between
      healthy and pathological TFJ kinematics and kinetics.

PMID- 21169023
TI  - Design, synthesis and biological evaluation of small molecule inhibitors of CD4
      gp120 binding based on virtual screening.
AB  - The low-molecular-weight compound JRC-II-191 inhibits infection of HIV-1 by
      blocking the binding of the HIV-1 envelope glycoprotein gp120 to the CD4 receptor
      and is therefore an important lead in the development of a potent viral entry
      inhibitor. Reported here is the use of two orthogonal screening methods, gold
      docking and ROCS shape-based similarity searching, to identify amine-building
      blocks that, when conjugated to the core scaffold, yield novel analogs that
      maintain similar affinity for gp120. Use of this computational approach to expand
      SAR produced analogs of equal inhibitory activity but with diverse capacity to
      enhance viral infection. The novel analogs provide additional lead scaffolds for
      the development of HIV-1 entry inhibitors that employ protein-ligand interactions
      in the vestibule of gp120 Phe 43 cavity.

PMID- 21169024
TI  - Synthesis of a covalent gemcitabine-(carbamate)-[anti-HER2/neu]
      immunochemotherapeutic and its cytotoxic anti-neoplastic activity against
      chemotherapeutic-resistant SKBr-3 mammary carcinoma.
AB  - Gemcitabine is a potent chemotherapeutic that exerts cytotoxic activity against
      several leukemias and a wide spectrum of carcinomas. A brief plasma half-life in
      part due to rapid deamination and chemotherapeutic-resistance frequently limit
      the utility of gemcitabine in clinical oncology. Selective 'targeted' delivery of
      gemcitabine represents a potential molecular strategy for simultaneously
      prolonging its plasma half-life and minimizing exposure of innocent tissues and
      organ systems. MATERIALS AND METHODS: Gemcitabine was combined in molar excess
      with N-[p-maleimidophenyl]-isocyanate (PMPI) so that the isocyanate moiety of
      PMPI which exclusively reacts with hydroxyl groups preferentially created a
      carbamate covalent bond at the terminal C(5)-methylhydroxy group of gemcitabine.
      Monoclonal immunoglobulin with binding-avidity specifically for HER2/neu was
      thiolated with 2-iminothiolane at the terminal epsilon-amine group of lysine
      amino acid residues. The gemcitabine-(carbamate)-PMPI intermediate with a
      maleimide moiety that exclusively reacts with reduced sulfhydryl groups was then
      combined with thiolated anti-HER2/neu monoclonal immunoglobulin. Western-blot
      analysis was utilized to delineate the molecular weight profile for gemcitabine
      (carbamate)-[anti-HER2/neu] while cell binding characteristics were determined by
      cell-ELISA utilizing SKBr-3 mammary carcinoma which highly over-expresses
      HER2/neu receptors. Cytotoxic anti-neoplastic potency of gemcitabine-(carbamate)
      [anti-HER2/neu] between the gemcitabine-equivalent concentrations of 10(-12) and
      10(-6)M was determined utilizing vitality staining analysis of chemotherapeutic
      resistant SKBr-3 mammary carcinoma. RESULTS: Gemcitabine-(carbamate)-[anti
      HER2/neu] was synthesized at a molar incorporation index of 1:1.1 (110%) and had
      a molecular weight of 150kDa that was indistinguishable from reference control
      immunoglobulin fractions. Cell-ELISA detected progressive increases in SKBr-3
      mammary carcinoma associated immunoglobulin with corresponding increases in
      covalent gemcitabine immunochemotherapeutic concentrations. The in vitro
      cytotoxic anti-neoplastic potency of gemcitabine-(carbamate)-[anti-HER2/neu] was
      approximately 20% and 32% at 10(-7) and 10(-6)M (gemcitabine-equivalent
      concentrations) after a 182-h incubation period. DISCUSSION: The investigations
      describes for the first time a methodology for synthesizing a gemcitabine anti
      HER2/neu immunochemotherapeutic by creating a covalent bond structure between the
      C(5)-methylhydroxy group of gemcitabine and thiolated lysine amino acid residues
      of monoclonal antibody or other biologically active protein fractions.
      Gemcitabine-(carbamate)-[anti-HER2/neu] possessed binding-avidity at HER2/neu
      receptors highly over-expressed by chemotherapeutic-resistant SKBr-3 mammary
      carcinoma. Alternatively, gemcitabine can be covalently linked at its C(5)
      methylhydroxy group to monoclonal immunoglobulin fractions that possess binding
      avidity for other receptors and membrane complexes uniquely highly over-expressed
      by a variety of neoplastic cell types. Compared to chemotherapeutic-resistant
      SKBr-3 mammary carcinoma, gemcitabine-(carbamate)-[anti-HER2/neu]
      immunochemotherapeutic is anticipated to exert higher levels of cytotoxic anti
      neoplastic potency against other neoplastic cell types like pancreatic carcinoma,
      small-cell lung carcinoma, neuroblastoma, glioblastoma, oral squamous cell
      carcinoma, cervical epithelioid carcinoma, or leukemia/lymphoid neoplastic cell
      types based on their reportedly greater sensitivity to gemcitabine and
      gemcitabine covalent conjugates.

PMID- 21169025
TI  - ED-XRF spectrometry-based comparative inorganic profile of leaf-derived in vitro
      calli and in vivo leaf samples of Phyllanthus amarus Schum. & Thonn.--a
      hepatoprotective herb.
AB  - The Energy Dispersive X-ray Fluorescence (ED-XRF) set-up incorporating a
      molybdenum secondary exciter was used for quantitative determination of major and
      minor elements in leaves of in vivo grown medicinal herb Phyllanthus amarus vis-a
      vis its leaf-derived in vitro callus culture. The elements such as K, Ca, V, Cr,
      Mn, Fe, Co, Ni, Cu, Zn, Se, Rb, Sr and Pb were identified, quantified and
      compared between both the sources. Experimental results revealed that, compared
      to the naturally grown herb, in vitro leaf-derived callus cultures were more
      efficient in accumulating inorganic elements, especially trace elements, which
      are essential for growth and development and more importantly for prevention and
      cure of diseases. This investigation on a medicinal plant species is the first of
      its kind to have used the ED-XRF technique to demonstrate a comparative account
      of the elemental profile of in vitro callus cultures with their in vivo donor in
      order to explore the possibility of exploiting the former as a viable alternative
      and a renewable source of phytochemicals.

PMID- 21169026
TI  - Characterization of copper/zinc and manganese superoxide dismutase in green
      bamboo (Bambusa oldhamii): Cloning, expression and regulation.
AB  - Bamboo is distinguished by its rapid growth, for growth more than 100 cm per day.
      Because of the rapid growth, tissues have significant ATP requirements, which
      results in intense reduction of oxygen and thus oxidative stress. For this
      reason, bamboo may have a special and efficient scavenger system to release the
      stress during fast cell division and elongation. Here, we investigated superoxide
      dismutase (SOD, E.C.1.15.1.1), the first line of antioxidant enzymes, in green
      bamboo (Bambusa oldhamii). The SOD activity profile in this species was complex,
      with 5 genes and 7 isozymes of CuZnSOD and 4 genes and 1 isozyme of MnSOD. We
      isolated one of each of the green bamboo CuZnSOD and MnSOD genes, and their
      activities were stable under a broad range of pH and temperature treatments, even
      at room temperature for more than 3 days. Bamboo SODs showed developmental and
      tissue-specific regulation, and both transcript and protein levels were
      responsive to abscisic acid, UV-B and high-light treatments. The complexity of
      the cis-elements in promoter regions implied that the regulation mechanisms of
      SOD might help accomplish the unique fast-growth phenotype of green bamboo.

PMID- 21169027
TI  - Localization of lipoxygenase activity on the oil bodies and in protoplasts using
      a novel fluorescence imaging method.
AB  - Lipoxygenase (linoleate:oxygen oxidoreductase; EC 1.13.11.12; LOX) catalyzes
      oxygenation of polyenoic fatty acids, which precedes the degradation of storage
      lipids during seed germination in sunflower. In the present work, it has been
      confirmed that 2',7'-dichlorodihydrofluorescein diacetate (H(2)DCFDA) produces
      fluorescence in presence of lipid hydroperoxides (LOX reaction products). This
      work provides new information on spatial localization of transiently enhanced LOX
      activity in protoplasts from 5 d old seedling cotyledons of sunflower (Helianthus
      annuus L. cv. Morden) by exploiting H(2)DCFDA as a probe for fluorescence
      detection from LOX activity sites. Use of LOX inhibitors [nordihydroguaiaretic
      acid (NDGA) and propyl gallate (PG)] confirms oil bodies as LOX activity sites.
      Oil body surface has been shown to possess LOX activity in 5 d old seedling
      cotyledons.

PMID- 21169028
TI  - Multidetector computed tomographic angiography diagnosis of a giant
      pseudoaneurysm of the left ventricular outflow tract.

PMID- 21169029
TI  - The impact of surgical ablation in patients with low ejection fraction, heart
      failure, and atrial fibrillation.
AB  - OBJECTIVE: Surgical ablation procedures that use the Cox-Maze procedure lesion
      set were shown to be very effective. However, many surgeons are reluctant to
      perform the procedure, especially in high-risk patients such as those with
      reduced left ventricular (LV) function. This study explored the potential impact
      of the Cox-Maze III/IV procedure on patients with low ejection fraction (EF<40%)
      and symptoms of heart failure experiencing atrial fibrillation (AF) who present
      for cardiac surgery. METHODS: A prospective study whereby patients with
      persistent or long-standing persistent AF who had surgical ablation were
      followed. Echocardiograms (echo) were obtained; patients with preoperative EF
      <40% were included. Health-related quality of life (HRQL-SF-12) and AF symptom
      severity were obtained at baseline and follow-up. Rhythm was captured by
      electrocardiogram (EKG) and 24-h Holter. RESULTS: In the past 5 years, 482
      patients had surgical ablation (424 full Cox-Maze) of whom 44 patients met the
      inclusion criteria; however, two patients did not have an available follow-up
      echo, leaving 42 patients for analysis. Mean age was 61.1 +/- 12.9 years, and
      additive European System for Cardiac Operative Risk Evaluation (EuroSCORE) of 7.5
      +/- 3.1. There was one operative death, there were no strokes or transient
      ischemic attacks (TIAs) at follow-up, and EF improved from 30 +/- 5.0% to 45 +/-
      13.0% at a mean of 1.5 +/- 11.3 months, postoperatively. The return to NSR at
      time of follow-up echo was 86% (35/40). The physical functioning HRQL scores
      improved (37.0 +/- 12.3 to 46.8 +/- 9.1, p = 0.02) at 12 months (population norm
      = 38.1 +/- 9.9) with a significant improvement in symptom severity. Kaplan-Meier
      event-free survival at 24 months was 87% (confidence interval (CI): 80.4-91.6)
      (events considered were redo valve replacement, ventricular assist device or
      death). CONCLUSIONS: This is a unique study assessing a high-risk group of
      patients. Surgical ablation in patients with low EF can be performed in a safe
      and effective way without added operative risk. Given the potential long-term
      clinical advantages of a successful surgical ablation in patients with low EF and
      heart failure, we believe that surgical ablation should be considered in such
      patients when they present to surgery.

PMID- 21169030
TI  - Comparison of surgical and interventional therapy of native and recurrent aortic
      coarctation regarding different age groups during childhood.
AB  - OBJECTIVE: The aim of the study was to analyze immediate results, rate of
      complications and re-interventions during medium-term outcome in pediatric
      patients with native or recurrent aortic coarctation. We focused on an age
      related therapeutic approach comparing surgical and trans-catheter treatment.
      METHODS: This is a retrospective, single-centre, clinical observational trial
      including 91 consecutive patients (age: 1 day-18 years) treated for native
      coarctation in 67 and recurrent aortic coarctation in 24 patients. Surgical
      treatment was performed in 56, trans-catheter treatment with balloon dilatation
      in 17, and by stent implantation in 18 patients. According to the age groups, we
      treated 48 children in group A (<6 months of age), 16 in group B (6 months-6
      years), and 27 in group C (>6 years). A total of 41 patients in group A were
      operated (85%), patients in group B received either surgical or trans-catheter
      treatment (50% vs 50%), and 16 patients in group C were treated by stent
      implantation (62%). RESULTS: Immediate results were excellent with a significant
      release of pressure gradient in all three age groups (64.7% in group A, 69.1% in
      group B, and 63.3% in group C). Complication rate and re-intervention rate
      (surgical and interventional) both were [corrected] comparable between the three
      age groups (complications: group A 8.3%, group B 6.3%, and group C 3.7%,
      [corrected] re-interventions: group A 16.6%, group B 18.8%, and group C 14.8%).
      [corrected] Midterm outcome after a median follow-up period of 17.5 months was
      satisfactory with a re-intervention-free survival after 17.5 months of 83.4%,
      81.2%, and 81.5% in group A, group B, and group C, respectively. CONCLUSIONS: The
      current strategy of an age-related therapy for native and recurrent aortic
      coarctation in our institution is surgery in infants <6 months (group A), either
      surgery or balloon dilatation in younger patients <6 years (group B), while in
      older children >6 years of age (group C) the trans-catheter treatment with stent
      implantation is an excellent alternative to surgery. Balloon dilatations showed
      limited results with an overall re-intervention rate of 53% and, therefore,
      should mainly be performed as a rescue procedure or in recurrent aortic
      coarctation in neonates.

PMID- 21169031
TI  - Seasonal variation influences outcomes following lung cancer resections.
AB  - OBJECTIVE: The effect of seasonal variation on postoperative outcomes following
      lung cancer resections is unknown. We hypothesized that postoperative outcomes
      following surgical resection for lung cancer within the United States would not
      be impacted by operative season. METHODS: From 2002 to 2007, 182507 isolated lung
      cancer resections (lobectomy (n = 147 937), sublobar resection (n = 21650), and
      pneumonectomy (n = 13916)) were evaluated using the Nationwide Inpatient Sample
      (NIS) database. Patients were stratified according to operative season: spring (n
      = 47382), summer (n = 46131), fall (n = 45370) and winter (n = 43624).
      Multivariate regression models were applied to assess the effect of operative
      season on adjusted postoperative outcomes. RESULTS: Patient co-morbidities and
      risk factors were similar despite the operative season. Lobectomy was the most
      common operation performed: spring (80.0%), summer (81.3%), fall (81.8%), and
      winter (81.1%). Lung cancer resections were more commonly performed at large,
      high-volume (>75th percentile operative volume) centers (P < 0.001). Unadjusted
      mortality was lowest during the spring (2.6%, P < 0.001) season compared with
      summer (3.1%), fall (3.0%) and winter (3.2%), while complications were most
      common in the fall (31.7%, P < 0.001). Hospital length of stay was longest for
      operations performed in the winter season (8.92 +/- 0.11 days, P < 0.001).
      Importantly, multivariable logistic regression revealed that operative season was
      an independent predictor of in-hospital mortality (P < 0.001) and of
      postoperative complications (P < 0.001). Risk-adjusted odds of in-hospital
      mortality were increased for lung cancer resections occurring during all other
      seasons compared with those occurring in the spring. CONCLUSIONS: Outcomes
      following surgical resection for lung cancer are independently influenced by time
      of year. Risk-adjusted in-hospital mortality and hospital length of stay were
      lowest during the spring season.

PMID- 21169032
TI  - TNF-alpha -308 genotypes are associated with TNF-alpha and TGF-beta1 mRNA
      expression in blood leucocytes of humans.
AB  - AIM: Tumor necrosis factor alpha (TNF-alpha) influences the pathogenesis of lung
      fibrosis and carcinogenesis in normal cells. Polymorphisms of this gene are
      suggested to be associated with susceptibility to lung-diseases. Additionally TNF
      alpha is postulated to play a significant role in regulating. Transforming growth
      factor (TGF-beta1) expression Therefore we investigated if the TNF-alpha or TGF
      beta1 gene expression level is different within the -308 TNF-alpha genotypes.
      METHODS: Quantitative Real-time PCR of TNF-alpha and TGF-beta1 was performed in
      178 Germans. Calculations of expression were made with the 2(-DeltaDeltaCT)
      method. Detection of the -308 promoter polymorphism of the TNF-alpha gene was
      performed by rapid capillary PCR with melting curve analysis. RESULTS: The
      relative TNF-alpha mRNA expression revealed significant differences between the
      TNF-alpha -308 homozygote wild-type G/G (0.00079+/-0.00011; n=113) and the
      heterozygote genotype G/A (0.0005+/-0.00008; n=52; p=0.030) as well as between
      homozygote wild-type G/G and the homozygote mutant A/A (0.00029+/-0.00009; n=5;
      p=0.004). The relative TGF-beta mRNA expression showed, similar to TNF-alpha, the
      highest mRNA expression was seen within the TNF-alpha -308 homozygote wild-types,
      while the lowest mRNA expression lay within the homozygote mutant-types.
      CONCLUSION: Our findings suggest that the G-allele of TNF-alpha -308 is
      associated with a significantly higher TNF-alpha mRNA expression compared to the
      A-allele and that this also reflects in TGF-beta expression. Therefore we support
      the thesis that TGF-beta is regulated by TNF-alpha.

PMID- 21169034
TI  - Lymphoscintigraphic localization of a high-output chylus leak after bilateral
      lung transplantation.
AB  - We report the case of a 59-year-old man who developed a high-output chylothorax
      after bilateral lung transplantation. For exact localization of the leak,
      lymphoscintigraphy was performed before re-thoracotomy by application of Tc-99m
      nanocolloid single-photon emission computed tomography (SPECT/CT), which showed a
      radioactive accumulation in the medial lower thoracic cavity, localized below the
      right upper pulmonary vein. This technique is actually an overly complex, time
      consuming procedure for proper surgical planning in selected cases.

PMID- 21169033
TI  - Interaction between GSTM1 genotype and IL-6 on mortality in older adults: results
      from the ilSIRENTE study.
AB  - BACKGROUND AND AIMS: The inflammatory process is related to oxidative stress and
      inflammation was proven to be a strong determinant of the aging process and to
      ultimately lead to death. The aim of the present study was to assess if, in a
      population of older adults, the effect of antioxidant genes GSTM1 and GSTT1
      genotypes on mortality may differ depending on levels of inflammation. METHODS:
      Data are from 353 older persons aged >=80 years enrolled in the ilSIRENTE study.
      Study population was divided into two groups computed based on the median value
      of serum IL-6 (low IL-6, n=177 and high IL-6, n=176). All participants were
      followed up for 48 months. RESULTS: Mean age of study participants was 85.8 years
      (Standard Deviation 4.8), 235 (66.6%) were women. Overall 48/177 participant
      (27.1%) in the low IL-6 group died during the study period, compared with 97/176
      (55.1%) in the high IL-6 group (p<0.001). After adjusting for potential
      confounders, GSTM1 wildtype had no effect on mortality in the low IL-6 group
      (RR=1.07; 95% CI 0.46-2.47), but it was associated with a significant lower
      mortality rate in the high IL-6 level (RR=0.33; 95% CI 0.15-0.69). Testing the
      interaction between IL-6 and GSTM1 genotype, we found a significant result
      (p=0.02). No significant effect of GSTT1 genotype on mortality was shown in
      participants with low and high IL-6 level. CONCLUSION: GSTM1 wildtype is
      associated with reduced mortality among older adults with high levels of
      inflammation, but not among those with low levels of inflammation.

PMID- 21169035
TI  - Effects of chronic treatment with valproate and oxcarbazepine on testicular
      development in rats.
AB  - PURPOSE: The aim of this study was to examine the potential effects of valproate
      (VPA) and oxcarbazepine (OXC) on testicular development in rats. METHODS: Forty
      two Wistar rats were randomly divided into three groups of 14 rats each. Each
      group received the following via gavage over 90 days: group 1, tap water (control
      group); group 2, VPA (300mg/kg/day); group 3, OXC (100mg/kg/day). After
      sacrifice, body, testicular and epididymidis weights were measured. Testes were
      sampled, fixed and processed, and quantitative morphometric analysis of Sertoli
      cells, spermatocytes and spermatids was performed in stages II, V and XII by
      histopathological examination. Immunohistochemical staining was performed to
      transform growth factor beta 1 (TGF-beta1) and p53, and the apoptotic index was
      assessed using the TUNEL method. RESULTS: Testis and relative testis weights were
      significantly lower in the VPA group compared to the control group (p<0.05).
      Spermatogonia, pachytene spermatocyte and round spermatocyte numbers decreased in
      all stages in both the VPA and OXC groups compared to the control group, though
      this was not statistically significant (p>0.05). Apoptotic cell counts and p53
      immunoreaction were significantly high and TGF-beta1 expression was significantly
      lower in the VPA group compared to that of the control group (p<0.05). In the OXC
      group, p53 immunoreaction and TGF-beta1 expression decreased compared to the
      control group, but this difference did not attain statistical significance
      (p>0.05). CONCLUSIONS: Our results show that VPA treatment from prepuberty to
      adulthood significantly negatively affects spermatogenesis, not only by reducing
      testicular weight, but also by increasing apoptotic death and p53 and decreasing
      TGF-beta1 activation. OXC has a minimal side effect on testicular development.

PMID- 21169036
TI  - Pilot association study of oxcarbazepine-induced mild cutaneous adverse reactions
      with HLA-B*1502 allele in Chinese Han population.
AB  - BACKGROUND: Recent study demonstrated that HLA-B*1502 was a common risk allele in
      aromatic antiepileptic drugs (AEDs) induced Stevens-Johnson syndrome and toxic
      epidermal necrolysis in Han Chinese. However, the association of AEDs-induced
      mild maculopapular eruption (MPE) with HLA-B*1502 remains unclear until recently.
      In the present study, we conducted a pilot study to detect a possible association
      of oxcarbazepine (OXC)-induced MPE with HLA-B*1502 allele in Chinese Han
      population. METHODS: We enrolled 90 subjects involving 9 patients with OXC
      induced MPE and two groups of controls, 9 OXC-tolerant and 72 normal controls.
      High-resolution HLA genotyping was performed by specific kit. The results of HLA
      genotyping are expressed as positive or negative for HLA-B*1502 allele.
      Differences in genotype frequencies between groups were assessed by the Fisher's
      exact test. RESULTS: Four cases were detected as positive for HLA-B*1502 amongst
      9 patients. However, only 1 subject was positive amongst 9 tolerant controls, and
      6 subjects were positive amongst 72 normal controls. The difference in HLA-B*1502
      allele frequencies between the MPE group and normal controls was statistically
      significant (OR: 8.8; 95% CI: 1.853-41.790; P=0.011). In addition, we also
      observed an increased frequency of HLA-B*1502 allele in patients (44.44%)
      compared with tolerant controls (11.11%), although it failed to reach statistical
      significance (P=0.294). CONCLUSIONS: Our findings indicate that HLA-B*1502 allele
      may contribute to the genetic susceptibility to OXC-induced MPE in Chinese Han
      population. In order to safer AEDs use, we recommend that HLA-B*1502 allele
      should be tested for patients with OXC-induced MPE before changing to other AEDs,
      and AEDs with similar chemical structure should be avoided in individuals who
      test positive for HLA-B*1502 allele. It should be pointed out that, however, our
      results may well be just by chance owing to the small sample size and should be
      further confirmed in future studies.

PMID- 21169037
TI  - Diagnosis and treatment of primary synovial cell sarcoma that occurred in the
      left mandible body: a case report and literature review.
AB  - OBJECTIVE: The authors describe a case of synovial sarcoma in the left mandible
      body. STUDY DESIGN: The primary tumor was investigated morphologically and
      immunohistochemically. The patient was treated with madibulectomy and lymph node
      dissection, which was followed by an immediate reconstruction of the left
      mandible with a revascularized osteomyocutaneous fibula free flap. RESULTS: The
      primary tumor was described as gingival sarcoma. The initial preoperative biopsy
      showed positive staining for cytokeratin, vimentin, smooth muscle actin, and
      desmin by immunohistochemistry. The definitive diagnosis of monophasic synovial
      sarcoma was established following postoperative excision biopsy. Antigens of S
      100 and CD99 displayed positive staining but epithelial membrane antigen, Bcl-2,
      and CD34 were negative. Also, no metastasis or other bone swelling was observed
      by radionuclide survey suggesting the left mandible was the primary lesion of
      occurrence. CONCLUSIONS: Synovial sarcoma is an uncommon soft tissue malignant
      neoplasm. This is the sixth case of primary synovial sarcoma occurring in the
      jaw.

PMID- 21169038
TI  - Interfacial adaptation of the Epiphany self-adhesive sealer to root dentin.
AB  - OBJECTIVE: The present study was designed to investigate interfacial quality
      between both Epiphany and Epiphany SE and the surrounding dentin having
      conventional gutta-percha/AH plus root filling as reference for comparison. STUDY
      DESIGN: A sample of 36 human maxillary canines was prepared and assigned to
      experimental groups of 12 teeth each, designated as G1, Resilon/Epiphany; G2,
      Resilon/Epiphany SE; and G3, gutta-percha/AH Plus. After the filling procedures,
      each specimen was horizontally sectioned at 3, 6, and 8 mm from the apex and a
      metallographic preparation was performed to enable the evaluation under Confocal
      Laser Scanning Microscopy (CLSM). The integrity of the interface was determined
      by calculating the ratio between the total sealer/dentin interface and the
      sealer/dentin interface that presented gap-containing regions. Additionally, the
      width of each gap was measured and pooled per each specimen for comparison.
      Statistical analysis was performed using nonparametric methods. RESULTS:
      Nonbonding AH Plus/gutta-percha root fillings showed a significantly higher
      amount of gap-free regions (P < .05). In the same way, nonbonding AH plus root
      fillings displayed significantly narrower gaps compared with the 2 adhesive root
      filling groups (P < .05). CONCLUSIONS: Under the present in vitro conditions, the
      quality of the interfacial adaptation of the current adhesive root fillings is
      compromised even when teeth with simple anatomic features were obturated under
      well-monitored laboratory conditions.

PMID- 21169039
TI  - Identification of internal control genes for quantitative expression analysis by
      real-time PCR in bovine peripheral lymphocytes.
AB  - Gene expression studies in blood cells, particularly lymphocytes, are useful for
      monitoring potential exposure to toxicants or environmental pollutants in humans
      and livestock species. Quantitative PCR is the method of choice for obtaining
      accurate quantification of mRNA transcripts although variations in the amount of
      starting material, enzymatic efficiency, and the presence of inhibitors can lead
      to evaluation errors. As a result, normalization of data is of crucial
      importance. The most common approach is the use of endogenous reference genes as
      an internal control, whose expression should ideally not vary among individuals
      and under different experimental conditions. The accurate selection of reference
      genes is therefore an important step in interpreting quantitative PCR studies.
      Since no systematic investigation in bovine lymphocytes has been performed, the
      aim of the present study was to assess the expression stability of seven
      candidate reference genes in circulating lymphocytes collected from 15 dairy
      cows. Following the characterization by flow cytometric analysis of the cell
      populations obtained from blood through a density gradient procedure, three
      popular softwares were used to evaluate the gene expression data. The results
      showed that two genes are sufficient for normalization of quantitative PCR
      studies in cattle lymphocytes and that YWAHZ, S24 and PPIA are the most stable
      genes.

PMID- 21169040
TI  - Culicoides species associated with sheep in the Netherlands and the effect of a
      permethrin insecticide.
AB  - Culicoides spp. act as vectors for a number of viral diseases of animals
      including bluetongue in sheep. The aims of this study were to determine: (1)
      which Culicoides spp. are associated with sheep in The Netherlands; (2) the time
      of the day when they are most active; and (3) the effect of treatment of animals
      with a permethrin insecticide. Two pairs of sheep were each housed within
      mosquito tents of either one or two layers of netting and all trapped Culicoides
      spp. were identified microscopically. For the permethrin insecticide study, one
      of two pairs of sheep was treated with 3.6% permethrin and all animals were
      housed in tents of similar design. Of the 6210 midges captured, 54.1% were
      identified as C. chiopterus and 42.7% as C. obsoletus. C. imicola was not
      identified. The average insect feeding rate was 35-40% and midge activity was
      greatest around sunset. Permethrin treatment reduced the number of midges
      captured by 50% and also resulted in a decrease in the percentage of midges that
      had fed. The findings provide useful information on the behaviour and
      distribution of Culicoides spp. that will facilitate the development of
      appropriate control strategies to minimise the risk of insect-vector borne virus
      diseases such as bluetongue.

PMID- 21169041
TI  - External characteristics of the lateral aspect of the hoof differ between non
      lame and lame horses.
AB  - During a pre-purchase examination (PPE) there is always a debate about how
      clinical findings of the hoof different from ideal should be interpreted in
      relation to future lameness risk and/or unsuitability of the horse for the
      potential purchaser. The objectives of this study were to describe and compare
      external angular measurements, linear ratios and hoof capsule characteristics of
      non-lame and lame feet. Photographs of feet from 300 horses with foot pain and 25
      non-lame horses were analysed. Hoof wall, heel and coronary band angles and hoof
      wall length and height, weight-bearing length, coronary band length and height of
      the coronary band at dorsal and palmar locations were measured and expressed as
      linear ratios. Mean hoof wall, heel and coronary band angles were larger in lame
      compared with non-lame feet; only the ratio of dorsal to palmar coronary band
      heights and the shape of the coronary band were significantly different between
      lame and non-lame horses. Growth rings were divergent and horn tubules were non
      parallel in lameness of >3 months. At a PPE, a larger ratio of dorsal to palmar
      coronary band heights in one limb may be indicative of previous lameness in that
      foot. Changes in coronary band shape and divergent growth rings and horn tubules
      would suggest a longer duration.

PMID- 21169042
TI  - Guillain-Barre syndrome as a prominent cause of childhood acute flaccid paralysis
      in post polio eradication era in Egypt.
AB  - Guillain-Barre syndrome often follows an antecedent gastrointestinal or
      respiratory illness but, in rare cases, follows vaccination. This study was
      conducted to identify preceding events, demographic, clinical characteristics and
      prognostic factors of childhood Guillain-Barre syndrome after post-poliomyelitis
      eradication era in Egypt. This is a prospective study of all children with GBS
      (no = 50) admitted to pediatric Cairo University Hospital between January 2006
      and June 2007 (70.42% of all acute flaccid paralysis patients during this
      period). Upper respiratory infection was the most common preceding event (24%)
      while only 4 patients (8%) reported antecedent oral polio vaccine. Motor deficit
      was frequent and severe (quadriparesis in 92% and paraparesis in 8%). Autonomic
      dysfunction was recorded in 32% of patients. Forty two percent of patients had
      poor outcome with 16% deaths. Presence of severe disability on admission and on
      nadir, cranial nerve affection or the need for mechanical ventilator were found
      to be significant predictors for poor outcome.

PMID- 21169043
TI  - Spinach--a software library for simulation of spin dynamics in large spin
      systems.
AB  - We introduce a software library incorporating our recent research into efficient
      simulation algorithms for large spin systems. Liouville space simulations
      (including symmetry, relaxation and chemical kinetics) of most liquid-state NMR
      experiments on 40+ spin systems can now be performed without effort on a desktop
      workstation. Much progress has also been made with improving the efficiency of
      ESR, solid state NMR and Spin Chemistry simulations. Spinach is available for
      download at http://spindynamics.org.

PMID- 21169045
TI  - The uptake of influenza and pneumococcal vaccination among immunocompromised
      patients attending rheumatology outpatient clinics.
AB  - PURPOSE AND OBJECTIVES: The patients using immunosuppressive agents are
      considered at high risk for acquiring different infections. Accordingly,
      international guidelines recommend vaccinating such patients against influenza
      and pneumococcal organisms. The aims of this study were two-fold: (1) to assess
      the influenza and pneumococcal vaccination uptake among our rheumatology
      outpatients who are immunosuppressed; (2) to identify the factors influencing
      immunisation uptake among our sample of patients. METHODS: This was a
      questionnaire-based study. Patients were eligible to partake in this study if
      they were using immunosuppressive drugs. During the study period (4 weeks), 337
      patients were screened, and 110 patients fulfilled the criteria for inclusion.
      RESULTS: Positive vaccination uptake of our cohort was as follows: common
      influenza alone (34%, 37 out of 110), pneumonia alone (11%, 12 out of 110), and
      both pneumococcal and influenza vaccination (11%). The status of influenza A
      (H1N1) vaccination was not recorded as a part of this audit. The two most common
      reasons cited by patients for non-uptake of vaccinations were: 'not offered' and
      'thought it was unnecessary'. Of 37 patients who had influenza vaccination, 33
      patients (89%) had additional risk factors, and there were only four patients who
      had influenza vaccine solely because they were taking immunosuppressive drugs.
      All pneumococcal vaccinated patients (n=12) were noted to have additional risk
      factors. CONCLUSION: There is suboptimal uptake of influenza and pneumococcal
      vaccinations among immunosuppressed patients attending rheumatology outpatient
      clinics. These results are a cause of concern given the morbidity and mortality
      of associated infections.

PMID- 21169044
TI  - Management of patients hospitalized for diabetic foot infection: results of the
      French OPIDIA study.
AB  - AIM: This study was an analysis of how diabetic patients with infected foot
      wounds are managed in hospital by departments specializing in diabetic foot
      pathology, including an evaluation of the outcome 1 year after discharge.
      METHODS: This was a prospective study of a cohort of patients hospitalized for
      diabetic foot infection at 38 hospital centres in France and followed-up for 1
      year after discharge. RESULTS: Altogether, 291 patients were included (73% male;
      85% type 2 diabetes; mean age: 64.3+/-11.7 years). Most of the wounds were
      located on the toes and forefoot, and infection was most often graded as
      moderate; nevertheless, in about 50% of patients, osteomyelitis was suspected.
      Also, 87% of patients had peripheral neuropathy and 50-62% had peripheral artery
      disease. Gram-positive cocci, and Staphylococcus aureus in particular, were by
      far the most frequently isolated microorganisms. During hospitalization, lower
      limb amputation was performed in 35% of patients; in 52%, the wound healed or had
      a favourable outcome. A year after discharge, 150 non-amputated patients were
      examined: at this time, 19% had to undergo amputation, whereas 79% had healed
      their wounds with no relapse. Risk factors for amputation were location (toes),
      severity of the wound and presence of osteomyelitis. Peripheral artery disease
      was associated with a poor prognosis, yet was very often neglected. CONCLUSION:
      In spite of being managed at specialized centres that were, in general, following
      the agreed-upon published guidelines, the prognosis for diabetic foot infection
      remains poor, with a high rate (48%) of lower-limb amputation.

PMID- 21169046
TI  - Extraskeletal effects of vitamin D: facts, uncertainties, and controversies.
AB  - Vitamin D was long viewed as a hormone acting chiefly to regulate calcium
      phosphate metabolism and bone mineralization. Over the last decade, however,
      basic science and clinical researchers have produced a bewildering amount of
      information on the extraskeletal effects of vitamin D. This article is a review
      of the clinical and biological actions of vitamin D including effects on the
      immune system, auto-immune diseases, infections, cancer, metabolic syndrome, fall
      risk, cognitive function, and muscle function.

PMID- 21169047
TI  - Cardiac 123I-MIBG accumulation in Parkinson's disease differs in association with
      REM sleep behavior disorder.

PMID- 21169049
TI  - Managing idiopathic Parkinson's disease in patients with schizophrenic disorders.
AB  - There is very little data on the treatment of idiopathic Parkinson's disease
      (IPD) in patients with schizophrenia. Since schizophrenia is treated primarily
      with dopamine receptor blocking medications, it is unknown if the beneficial
      effects of anti-PD medications might be blocked or if the drugs may trigger
      worsened psychosis. A chart review was performed which identified nine patients
      with schizophrenia and presumed Idiopathic Parkinson's Disease (IPD). None of the
      patients suffered worsened psychosis from l-Dopa or a dopamine agonist if taking
      antipsychotics, and motor response did not appear blunted.

PMID- 21169048
TI  - Lack of association of dairy food, calcium, and vitamin D intake with the risk of
      Parkinson's disease: a case-control study in Japan.
AB  - Three previous cohort studies in the USA reported that dairy product consumption
      was significantly associated with an increased risk of Parkinson's disease (PD)
      in men, but not in women. We examined the relationship between consumption of
      dairy products, calcium, and vitamin D and the risk of PD using data from a
      multicenter hospital-based case-control study in Japan. Included were 249 cases
      within 6 years of onset of PD based on the UK PD Society Brain Bank clinical
      diagnostic criteria. Controls were 368 inpatients and outpatients without a
      neurodegenerative disease. Information on dietary factors was collected using a
      validated self-administered diet history questionnaire. Adjustment was made for
      sex, age, region of residence, pack-years of smoking, years of education, body
      mass index, and dietary factors including cholesterol, dietary glycemic index,
      vitamin E, beta-carotene, vitamin B(6), caffeine, iron, and alcohol. Total dairy
      product consumption was not materially associated with the risk of PD (P for
      trend = 0.62). No evident relationships were observed between intake of milk,
      yogurt, cheese, or ice cream and the risk of PD (P for trend = 0.75, 0.63, 0.59,
      and 0.35, respectively). There were no measurable associations between
      consumption of calcium or vitamin D and PD (P for trend = 0.37 and 0.69,
      respectively). No significant interactions were observed between the dietary
      exposures and sex regarding PD. Our results suggest that intake of dairy
      products, calcium, and vitamin D was not related to PD, regardless of sex.
      However, such null relationships might be a consequence of PD.

PMID- 21169050
TI  - "Food is directed to the area": African Americans' perceptions of the
      neighborhood nutrition environment in Pittsburgh.
AB  - Studies have shown racial disparities in neighborhood access to healthy food in
      the United States. We used a mixed methods approach employing geographic
      information systems, focus groups, and a survey to examine African Americans'
      perceptions of the neighborhood nutrition environment in Pittsburgh. We found
      that African Americans perceive that supermarkets serving their community offer
      produce and meats of poorer quality than branches of the same supermarket serving
      White neighborhoods (p<0.001). Unofficial taxis or jitneys, on which many African
      Americans are reliant, provide access from only certain stores; people are
      therefore forced to patronize these stores even though they are perceived to be
      of poorer quality. Community-generated ideas to tackle the situation include
      ongoing monitoring of supermarkets serving the Black community. We conclude that
      stores should make every effort to be responsive to the perceptions and needs of
      their clients and provide an environment that enables healthy eating.

PMID- 21169051
TI  - New frontiers in the treatment of liposarcoma, a therapeutically resistant
      malignant cohort.
AB  - The adipogenic origin-derived liposarcoma (LPS) family is the most common soft
      tissue sarcoma histological subtype. This group is composed of three categories
      as per the 2002 WHO guidelines: (1) well-differentiated and dedifferentiated
      liposarcoma (WDLPS/DDLPS); (2) myxoid and round cell liposarcoma (MLS and RCL);
      and (3) pleomorphic liposarcoma (PLS). While clustered together, these
      histological subtypes are widely diverse in their clinical, pathological, and
      molecular characteristics. In general, surgery still remains the mainstay of LPS
      therapy and the only approach offering the potential of cure. Effective
      therapeutic strategies for locally advanced and metastatic disease are currently
      lacking and are crucially needed. With the current gradually increasing knowledge
      of LPS genetic- and epigenetic-associated deregulations, the ultimate goal is to
      develop drugs that can specifically eliminate LPS cells while sparing normal
      tissues. This tumor-tailored target-orientated approach will hopefully result in
      a significant improvement in the outcome of patients suffering from these poor
      prognosis malignancies.

PMID- 21169052
TI  - A complete 1H and 13C NMR data assignment for 3-phenylmethylene-1H,3H-naphtho
      [1,8-c,d]-pyran-1-one.
AB  - Complete assignments of the 1H and 13C NMR chemical shifts for 3-phenylmethylene
      1H,3H-naphtho-[1,8-c,d]-pyran-1-one were done by means of one- and two
      dimensional NMR techniques, including 1H-(1)H COSY, HMQC and HMBC spectra. Ab
      initio quantum chemistry calculations and a shift prediction by an incremental
      method provided values close to the proposed assignments. All mid-IR spectral
      bands are given as reference data. The DRIFT FTIR, ATR FTIR and Raman spectra are
      given as a Supplementary data in JCAMP-DX format, version 4.24. In addition, a
      method of compound's synthesis, that has the product yield higher as compared to
      already known data in the literature, is given.

PMID- 21169053
TI  - Human papillomavirus is detectable in Barrett's esophagus and esophageal
      carcinoma but is unlikely to be of any etiologic significance.
AB  - Barrett's esophagus (BE), a known precursor of esophageal adenocarcinoma has
      recently been associated with human papillomavirus (HPV). p16(INK4a) expression
      is a recognized surrogate marker of HPV infection in the cervix. OBJECTIVES: This
      study has assessed the possible role of human papillomavirus (HPV) infection in
      BE and esophageal adenocarcinoma, in the North American population by screening
      esophageal tissues for HPV by a combination of assays. STUDY DESIGN: Formalin
      fixed, paraffin-embedded blocks from cases of Barrett's esophagus (n=84),
      esophageal adenocarcinoma (n=36) and normal gastro-esophageal junction (n=29)
      were examined for HPV by PCR, chromogenic in situ hybridization, and p16(INK4a)
      immunohistochemistry. RESULTS: HPV DNA was detected by PCR in 23 of 84 (27.4%) BE
      cases, 11 of 36 (31%) cases of adenocarcinoma and in 7 of 29 (24%) normal control
      cases (p=0.82). p16(INK4a) staining was positive in 10 (12%) cases of BE, 15
      (42%) cases of adenocarcinoma and 6 (21%) cases of the control group. Positive
      p16(INK4a) staining was not statistically different between the three groups
      whether positive or negative for HPV DNA (p=0.91 and p=0.91 respectively).
      Similarly, negative p16(INK4a) staining did not show a difference between the
      three groups for whether positive or negative for HPV DNA (p=0.50 and p=0.28,
      respectively). HPV was not detected by CISH in the adenocarcinomas while in BE
      and control groups, CISH was non-contributory. CONCLUSIONS: These data suggest
      that while HPV is detectable in a subset of esophageal lesions and tumors, the
      HPV detected is unlikely to be of etiologic significance or a factor accounting
      for the increase in BE and esophageal adenocarcinoma cases in the United States.

PMID- 21169054
TI  - Detailed understanding of enhanced specific productivity in Chinese hamster ovary
      cells at low culture temperature.
AB  - The specific productivity of tumor necrosis factor receptor-immunoglobulin G1 Fc
      fusion (TNFR-Fc) (q(TNFR-Fc)) in Chinese hamster ovary (CHO) cells at 30 degrees
      C was approximately 5-fold higher than that at 37 degrees C. To investigate
      reasons for increased q(TNFR-Fc) at low culture temperature, TNFR-Fc mRNA levels
      were determined by real-time PCR. It was found that like q(TNFR-Fc), the relative
      TNFR-Fc mRNA level was increased by lowering culture temperature, and more
      importantly, the kinetics of the increase in TNFR-Fc mRNA levels were in
      accordance with the changes in q(TNFR-Fc). The results demonstrated that the
      increased transcriptional level of TNFR-Fc was responsible for the increased
      q(TNFR-Fc) at low culture temperature. Enhanced levels of mRNA could derive from
      increased gene copy number, improved mRNA stability, or enhanced transcriptional
      rate. There was not a big change of gene copy number by lowering culture
      temperature. The transcriptional rate of TNFR-Fc was slightly decreased at 30
      degrees C, compared to 37 degrees C. However, mRNA stability of TNFR-Fc was
      significantly improved by lowering culture temperature. The half-life of TNFR-Fc
      mRNA was 5.55 h at 30 degrees C, whereas that was 3.69h at 37 degrees C. Taken
      together, the reasons for the increased q(TNFR-Fc) in CHO cells at low culture
      temperature were mainly the enhanced TNFR-Fc mRNA levels, which resulted from the
      improved mRNA stability, rather than the changes in the gene copy number or the
      transcriptional rate.

PMID- 21169055
TI  - Biotransformation of quinazoline and phthalazine by Aspergillus niger.
AB  - Cultures of Aspergillus niger NRRL-599 in fluid Sabouraud medium were grown with
      quinazoline and phthalazine for 7 days. Metabolites were purified by high
      performance liquid chromatography and identified by mass spectrometry and proton
      nuclear magnetic resonance spectroscopy. Quinazoline was oxidized to 4
      quinazolinone and 2,4-quinazolinedione, and phthalazine was oxidized to 1
      phthalazinone.

PMID- 21169056
TI  - Incidence and severity of neck injury in Rugby Union: a systematic review.
AB  - Objectives. To collate and appraise incidence and severity data for neck injury
      in Rugby Union. To report risk factors for neck injury in Rugby Union that are
      supported by incidence and severity data. Design. Systematic review. Methods.
      Original journal articles were retrieved from electronic searches of AusportMed,
      AUSPORT, Scopus, Medline (Ovid), CINAHL, Mantis, and Pubmed databases and
      relevant bibliographic hand searches. Selection criteria were restricted to: (a)
      prospective study designs including cohort, case-control, and intervention
      methodologies; (b) populations of Rugby Union players, either male or female of
      any age; (c) studies must report on neck injury incidence and/or severity
      specifically; (d) articles with republished neck injury data were excluded. The
      STROBE Statement was adapted for the quality assessment of included studies and
      categorised as either poor, moderate or good. Results. Thirty-three original
      articles met the selection criteria. Wide variation of injury and exposure
      definitions and population sampling was identified in the included articles. Neck
      injury incidence ranged between 0.26 (CI: 0.08, 0.93) and 9.17 (CI: 1.89, 26.81)
      per 1000 player hours for mixed populations that adopted an all inclusive sports
      injury definition. There is a paucity of severity data and analytical data which
      evaluates causal roles of risk factors for neck injury in Rugby Union.
      Conclusions. Meaningful understanding of neck injury incidence and severity in
      Rugby Union is restricted to a few studies which adopt comparable methodological
      construct. This paper provides an index for future neck injury studies in Rugby
      Union.

PMID- 21169057
TI  - Injury prevention target groups in soccer: injury characteristics and incidence
      rates in male junior and senior players.
AB  - To identify target groups for injury prevention in male amateur soccer players
      under 35 years of age. A computer-assisted telephone survey with a 12-month
      recall period for injuries in a representative sample of Dutch citizens from the
      Injuries and Physical Activity Netherlands (IPAN)-database. A comparison of the
      volume of soccer injuries, the incidence and the need for medical attention per
      level of exposure and age category. The incidence in seniors was twice that of
      juniors (17.5% versus 8.1%; odds ratio (OR=2.4). In juniors the overall incidence
      was lowest in the category with the least amount of soccer exposure time (0-3 h:
      2.9%; 3-5 h: 13.0%; 5+ h: 12.3%). A comparable result was found in seniors: (0-3
      h: 12.0%; 3-5 h: 21.6%; 5+ h: 21.5%). Within each level of soccer exposure, a
      different incidence was found in juniors and seniors (0-3 h: OR=4.6; 3-5 h:
      OR=1.8; 5+ h: OR=1.9). Ankle, knee and upper leg injuries were most common
      (59.9%). Contusions, strains and sprains dominated (78.1%). Body region and type
      of injuries were similar in both age categories. Medical treatment for injuries
      was equally necessary in both age groups. Senior male amateur soccer players and
      particularly the more skilled seniors (involved in soccer at least 3 h per week),
      should be primarily targeted for studies on injury risk factors and prevention
      programs.

PMID- 21169058
TI  - Acute repair of traumatic tricuspid valve regurgitation aided by three
      dimensional echocardiography.
AB  - A 54 year-old man without prior cardiac history was involved in a motor vehicle
      accident. His heart rate was 100/min and blood pressure 128/78 mmHg. He
      complained of anterior chest pain, and on examination had a loud pan-systolic
      murmur with no clinical signs of heart failure. Three-dimensional trans
      oesophageal echocardiography (3D-TOE) demonstrated partial rupture of the
      inferior head of the anterior papillary muscle (when 2D-TOE did not), causing
      severe tricuspid regurgitation. This was successfully repaired. Tricuspid valve
      insufficiency is a rare, but well documented, complication of blunt chest trauma.
      The majority of cases of tricuspid regurgitation caused by blunt trauma are
      diagnosed and treated late after the traumatic event. Acute diagnosis is less
      common but possible with a high level of vigilance, and is greatly aided by
      clinical indicators of cardiac injury. We describe a case of acute repair of
      traumatic tricuspid insufficiency, in which diagnosis and surgical planning were
      greatly aided by 3D-TOE.

PMID- 21169059
TI  - Cetuximab in NSCLC: another trial needed.

PMID- 21169060
TI  - First-cycle rash and survival in patients with advanced non-small-cell lung
      cancer receiving cetuximab in combination with first-line chemotherapy: a
      subgroup analysis of data from the FLEX phase 3 study.
AB  - BACKGROUND: The randomised phase 3 First-Line Erbitux in Lung Cancer (FLEX) study
      showed that the addition of cetuximab to cisplatin and vinorelbine significantly
      improved overall survival compared with chemotherapy alone in the first-line
      treatment of advanced non-small-cell lung cancer (NSCLC). The main cetuximab
      related side-effect was acne-like rash. Here, we assessed the association of this
      acne-like rash with clinical benefit. METHODS: We did a subgroup analysis of
      patients in the FLEX study, which enrolled patients with advanced NSCLC whose
      tumours expressed epidermal growth factor receptor. Our landmark analysis
      assessed if the development of acne-like rash in the first 21 days of treatment
      (first-cycle rash) was associated with clinical outcome, on the basis of patients
      in the intention-to-treat population alive on day 21. The FLEX study is
      registered with ClinicalTrials.gov, number NCT00148798. FINDINGS: 518 patients in
      the chemotherapy plus cetuximab group-290 of whom had first-cycle rash-and 540
      patients in the chemotherapy alone group were alive on day 21. Patients in the
      chemotherapy plus cetuximab group with first-cycle rash had significantly
      prolonged overall survival compared with patients in the same treatment group
      without first-cycle rash (median 15.0 months [95% CI 12.8-16.4] vs 8.8 months
      [7.6-11.1]; hazard ratio [HR] 0.631 [0.515-0.774]; p<0.0001). Corresponding
      significant associations were also noted for progression-free survival (median
      5.4 months [5.2-5.7] vs 4.3 months [4.1-5.3]; HR 0.741 [0.607-0.905]; p=0.0031)
      and response (rate 44.8% [39.0-50.8] vs 32.0% [26.0-38.5]; odds ratio 1.703
      [1.186-2.448]; p=0.0039). Overall survival for patients without first-cycle rash
      was similar to that of patients that received chemotherapy alone (median 8.8
      months [7.6-11.1] vs 10.3 months [9.6-11.3]; HR 1.085 [0.910-1.293]; p=0.36). The
      significant overall survival benefit for patients with first-cycle rash versus
      without was seen in all histology subgroups: adenocarcinoma (median 16.9 months,
      [14.1-20.6] vs 9.3 months [7.7-13.2]; HR 0.614 [0.453-0.832]; p=0.0015), squamous
      cell carcinoma (median 13.2 months [10.6-16.0] vs 8.1 months [6.7-12.6]; HR 0.659
      [0.472-0.921]; p=0.014), and carcinomas of other histology (median 12.6 months
      [9.2-16.4] vs 6.9 months [5.2-11.0]; HR 0.616 [0.392-0.966]; p=0.033).
      INTERPRETATION: First-cycle rash was associated with a better outcome in patients
      with advanced NSCLC who received cisplatin and vinorelbine plus cetuximab as a
      first-line treatment. First-cycle rash might be a surrogate clinical marker that
      could be used to tailor cetuximab treatment for advanced NSCLC to those patients
      who would be most likely to derive a significant benefit.

PMID- 21169061
TI  - Plasmodium sensitivity to artemisinins: magic bullets hit elusive targets.
AB  - Artemisinins are efficacious antimalarial drugs widely employed as first-line
      treatment in endemic countries under the form of combined therapies. Different
      molecular modes of action have been postulated to explain the parasiticidal
      effect of these compounds; however, none has been unequivocally accepted, and
      their physiological relevance is still questioned. Similarly, no definite genetic
      determinant of Plasmodium sensitivity to artemisinins has been identified so far.
      A better understanding of the mode of action of artemisinins and the genetic
      basis of laboratory-induced or field-observed altered susceptibility is crucial
      for malaria control. In this review different models of artemisinins' molecular
      action are briefly presented, focusing on recent advances, and the evidence of
      potential association between various gene polymorphisms and artemisinin
      resistance is comprehensively reviewed.

PMID- 21169062
TI  - In my day II: Reflecting on the transformative potential of incorporating
      celebrations into the nursing curriculum.
AB  - Understanding one's history is a powerful way to build a sense of belonging,
      identity and connection. Similarly, history learning can be a powerful component
      in the core curriculum for undergraduate nursing. History learning develops
      thinking skills transferable to and necessary in nursing practice. Additionally,
      awareness about the profession's struggles, achievements and enduring concerns is
      raised and belief that an individual or group can have influence is affirmed.
      Perseverance, commitment and seeing the big picture gives a nurse's career
      meaning and purpose. All of these factors can produce a transformed perspective
      in today's learners, who are often present-focused, isolated and disconnected
      from the past and the profession. This paper reports an evaluation of a second
      interactive learning experience held at the University of the Sunshine Coast to
      celebrate International Nurses Day 2010. In a previous paper, we shared our
      initial insights after the success of the first event, and now build upon those
      insights by examining the transformative learning provoked by the experience,
      from the points of view of students and staff.

PMID- 21169063
TI  - Nuclear transfer to prevent mitochondrial DNA disorders: revisiting the debate on
      reproductive cloning.
AB  - Preclinical experiments are currently performed to examine the feasibility of
      several types of nuclear transfer to prevent mitochondrial DNA (mtDNA) disorders.
      Whereas the two most promising types of nuclear transfer to prevent mtDNA
      disorders, spindle transfer and pronuclear transfer, do not amount to
      reproductive cloning, one theoretical variant, blastomere transfer does. This
      seems the most challenging both technically and ethically. It is prohibited by
      many jurisdictions and also the scientific community seems to avoid it.
      Nevertheless, this paper examines the moral acceptability of blastomere transfer
      as a method to prevent mtDNA disorders. The reason for doing so is that most
      objections against reproductive cloning refer to reproductive adult cloning,
      while blastomere transfer would amount to reproductive embryo cloning. After
      clarifying this conceptual difference, this paper examines whether the main non
      safety objections brought forward against reproductive cloning also apply in the
      context of blastomere transfer. The conclusion is that if this variant were to
      become safe and effective, dismissing it because it would involve reproductive
      cloning is unjustified. Nevertheless, as it may lead to more complex ethical
      appraisals than the other variants, researchers should initially focus on the
      development of the other types of nuclear transfer to prevent mtDNA disorders.

PMID- 21169064
TI  - Hypothermia and the complexity of trials in patients with traumatic brain injury.

PMID- 21169065
TI  - Very early hypothermia induction in patients with severe brain injury (the
      National Acute Brain Injury Study: Hypothermia II): a randomised trial.
AB  - BACKGROUND: The inconsistent effect of hypothermia treatment on severe brain
      injury in previous trials might be because hypothermia was induced too late after
      injury. We aimed to assess whether very early induction of hypothermia improves
      outcome in patients with severe brain injury. METHODS: The National Acute Brain
      Injury Study: Hypothermia II (NABIS: H II) was a randomised, multicentre clinical
      trial of patients with severe brain injury who were enrolled within 2.5 h of
      injury at six sites in the USA and Canada. Patients with non-penetrating brain
      injury who were 16-45 years old and were not responsive to instructions were
      randomly assigned (1:1) by a random number generator to hypothermia or
      normothermia. Patients randomly assigned to hypothermia were cooled to 35 degrees
      C until their trauma assessment was completed. Patients who had none of a second
      set of exclusion criteria were either cooled to 33 degrees C for 48 h and then
      gradually rewarmed or treated at normothermia, depending upon their initial
      treatment assignment. Investigators who assessed the outcome measures were masked
      to treatment allocation. The primary outcome was the Glasgow outcome scale score
      at 6 months. Analysis was by modified intention to treat. This trial is
      registered with ClinicalTrials.gov, NCT00178711. FINDINGS: Enrolment occurred
      from December, 2005, to June, 2009, when the trial was terminated for futility.
      Follow-up was from June, 2006, to December, 2009. 232 patients were initially
      randomised a mean of 1.6 h (SD 0.5) after injury: 119 to hypothermia and 113 to
      normothermia. 97 patients (52 in the hypothermia group and 45 in the normothermia
      group) did not meet any of the second set of exclusion criteria. The mean time to
      35 degrees C for the 52 patients in the hypothermia group was 2.6 h (SD 1.2) and
      to 33 degrees C was 4.4 h (1.5). Outcome was poor (severe disability, vegetative
      state, or death) in 31 of 52 patients in the hypothermia group and 25 of 56 in
      the normothermia group (relative risk [RR] 1.08, 95% CI 0.76-1.53; p=0.67). 12
      patients in the hypothermia group died compared with eight in the normothermia
      group (RR 1.30, 95% CI 0.58-2.52; p=0.52). INTERPRETATION: This trial did not
      confirm the utility of hypothermia as a primary neuroprotective strategy in
      patients with severe traumatic brain injury.

PMID- 21169066
TI  - Clinical experience with alpha-galactosylceramide (KRN7000) in patients with
      advanced cancer and chronic hepatitis B/C infection.
AB  - For over a century, research has sought ways to boost the immune system in order
      to eradicate tumors and viruses that exist after escaping immunosurveillance. For
      the treatment of cancer and hepatitis immunotherapeutic strategies have overall
      had limited clinical success. An urgent need exists therefore to introduce more
      effective therapeutic approaches. Invariant (i)NKT cells constitute a conserved T
      lymphocyte lineage with dominant immunoregulatory, antitumor and antiviral
      effector cell properties. iNKT specifically recognize the glycolipid alpha
      galactosylceramide in the context of CD1d resulting in their activation.
      Activated iNKT can promote the development of a long-lasting Th1 biased
      proinflammatory immune response as demonstrated in multiple tumor-metastasis and
      viral infection models. Here, we will provide a brief overview of the preclinical
      data of alpha-galactosylceramide that formed the basis for subsequent clinical
      trials in patients with advanced cancer and chronic hepatitis B/C, and elaborate
      on our own clinical experience with alpha-galactosylceramide in these patient
      groups.

PMID- 21169067
TI  - Temporal dynamics of anti-MOG antibodies in CNS demyelinating diseases.
AB  - Recent studies demonstrated the presence of autoantibodies to native myelin
      oligodendrocyte glycoprotein (MOG) in juvenile patients with acute disseminated
      encephalomyelitis (ADEM) and multiple sclerosis (MS). However, so far no
      longitudinal studies on anti-MOG antibodies have been performed. Therefore, we
      determined serum and CSF antibodies against native human MOG in 266 pediatric and
      adult subjects with ADEM, clinically isolated syndrome (CIS), MS, other
      neurological diseases (OND) and healthy controls (HC) and longitudinal samples of
      25 patients with ADEM, CIS, MS and OND using an immunofluorescence assay. We
      detected serum high-titer MOG IgG in 15/34 (44%) patients with ADEM, but only
      rarely in CIS (3/38, 8%), MS (2/89, 2%), OND (1/58, 2%) and HC (0/47).
      Longitudinal analysis of serum anti-MOG IgG showed different temporal dynamics of
      serum antibody responses in ADEM, CIS and MS and indicated an association of a
      favorable clinical outcome in ADEM with a decrease in antibody titers over time.

PMID- 21169068
TI  - Differential sympathetic activation induced by intermittent hypoxia and sleep
      loss in rats: Action of angiotensin (1-7).
AB  - The present study attempted to evaluate the effects of chronic intermittent
      hypoxia (CIH) associated with sleep restriction in hemodynamic parameters and the
      plasma renin-angiotensin system. Wistar-Hannover rats were submitted to isolated
      CIH exposure (1000-1600 h), sleep restriction (1600-1000 h), defined as 18-h
      paradoxical sleep deprivation followed by 6-h sleep permission period and CIH
      associated to sleep restriction for 21 days. The CIH and sleep restriction group
      showed a preferential increase in renal sympathetic nervous system (rSNA)
      associated with a reduction in plasma angiotensin (1-7) concentrations. However,
      CIH-sleep restriction rats did not modify rSNA and showed a higher angiotensin (1
      7) concentration when compared to isolated CIH and sleep restriction. These
      results suggest that CIH and sleep restriction impaired the cardiovascular
      system, and its association to sleep loss can modify these effects by partially
      restoring circulating angiotensin (1-7).

PMID- 21169069
TI  - Quantitation of ursolic acid in human plasma by ultra performance liquid
      chromatography tandem mass spectrometry and its pharmacokinetic study.
AB  - Ursolic acid is a hydroxy pentacyclic triterpene, which proved to have sedation,
      anti-inflammatory, antibacterial, antiulcer and anti-cancer activities. An ultra
      performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) method
      with high selectivity, sensitivity and throughput has been established and
      validated for quantitation of total ursolic acid in human plasma. Plasma samples
      were pretreated by liquid-liquid extraction with ethyl acetate and were
      chromatographed by an ACQUITY UPLC BEH C(8) column (100 mm*2.1 mm, I.D., 1.7 MUm)
      using mobile phase consisting of acetonitrile and 10 mM ammonium formate (90:10,
      v/v) at 0.2 mL/min. The duration of chromatography analysis was 3 min. The
      multiple reaction monitoring (MRM) was performed at m/z 455.1->455.0 for ursolic
      acid and m/z 469.3->425.2 for glycyrrhetinic acid (internal standard, IS) in the
      negative ion mode with electrospray ionization (ESI) source. The assay showed
      good linearity over the range of 10-5000 ng/mL for ursolic acid in human plasma
      with a lower limit of quantitation of 10 ng/mL. The mean extraction recovery was
      73.2+/-4.5% and the matrix ion suppression ranged from -11.4% to -5.6%. The intra
      and inter-day precisions were less than 7.0% and 7.2%, respectively, and the
      accuracy was within +/-2.0%. Ursolic acid was stable during the analysis and the
      storage period. The validated method has been successfully applied to a
      pharmacokinetic study after intravenous infusion of Ursolic Acid Nano-liposomes
      to healthy volunteers.

PMID- 21169070
TI  - DNA methylation patterns in luminal breast cancers differ from non-luminal
      subtypes and can identify relapse risk independent of other clinical variables.
AB  - The diversity of breast cancers reflects variations in underlying biology and
      affects the clinical implications for patients. Gene expression studies have
      identified five major subtypes- Luminal A, Luminal B, basal-like, ErbB2+ and
      Normal-Like. We set out to determine the role of DNA methylation in subtypes by
      performing genome-wide scans of CpG methylation in breast cancer samples with
      known expression-based subtypes. Unsupervised hierarchical clustering using a set
      of most varying loci clustered the tumors into a Luminal A majority (82%)
      cluster, Basal-like/ErbB2+ majority (86%) cluster and a non-specific cluster with
      samples that were also inconclusive in their expression-based subtype
      correlations. Contributing methylation loci were both gene associated loci (30%)
      and non-gene associated (70%), suggesting subtype dependant genome-wide
      alterations in the methylation landscape. The methylation patterns of significant
      differentially methylated genes in luminal A tumors are similar to those
      identified in CD24 + luminal epithelial cells and the patterns in basal-like
      tumors similar to CD44 + breast progenitor cells. CpG islands in the HOXA cluster
      and other homeobox (IRX2, DLX2, NKX2-2) genes were significantly more methylated
      in Luminal A tumors. A significant number of genes (2853, p < 0.05) exhibited
      expression-methylation correlation, implying possible functional effects of
      methylation on gene expression. Furthermore, analysis of these tumors by using
      follow-up survival data identified differential methylation of islands proximal
      to genes involved in Cell Cycle and Proliferation (Ki-67, UBE2C, KIF2C, HDAC4),
      angiogenesis (VEGF, BTG1, KLF5), cell fate commitment (SPRY1, OLIG2, LHX2 and
      LHX5) as having prognostic value independent of subtypes and other clinical
      factors.

PMID- 21169071
TI  - [Consensus Document on the differential diagnosis and therapeutic approach to
      recurrent fever by the Paediatric Infectology Society and the Paediatric
      Rheumatology Society].
AB  - Recurrent fever is a relatively common problem during childhood. Diagnosis is
      often easy and related to mild viral infections. However a small proportion of
      these cases originate from an underlying non-infectious process that is generally
      difficult to diagnose. In this paper we describe the differential diagnosis of
      recurrent or periodic fever versus other processes, with especial attention to
      autoinflammatory disorders (AD). AD are alterations of innate immunity, and they
      have been recently classified as an immunodeficiency. Anyhow, since infections
      are not present, these processes are different to the classic primary
      immunodeficiency. An important part of AD is of known genetic aetiology. The
      symptoms originate from an underlying inflammatory process and can have different
      clinical expressions. One of the most relevant groups is the hereditary syndromes
      of periodic fever. This group of diseases associates recurrent fever and several
      clinical symptoms with a relative periodicity, separated by intervals free or
      almost free of symptoms. We include the diagnostic criteria for some processes as
      well as the characteristics that should, eventually, lead to a genetic study.
      Although treatment should be individualised, we also include some general
      recommendations.

PMID- 21169072
TI  - [Different expression of the Asn264LysfsX35 mutation of the GNAS gene in a family
      with pseudohypoparathyroidism.].
AB  - Pseudohypoparathyroidism (PHP) is a heterogeneous group of endocrine diseases
      characterised by hypocalcaemia, hyperphosphataemia and resistance to PTH. There
      are different forms of PHP. PHP-Ia is the most frequent form and shows multi
      hormonal resistance, GNAS (Gs(alpha)) mutations and signs of Albrights hereditary
      osteodystrophy (AHO). PseudoPHP (PPHP) have isolated AHO without hormonal
      resistance and it is also caused by GNAS mutations. We present a family that
      share the same inactivating GNAS mutation (Asn264LysfsX35); the mother being
      affected with PPHP and the two daughters with PHP-Ia. We discuss the different
      clinical phenotypes and the dominant mode of inheritance with genetic imprinting
      where the phenotype of the offspring depends on the sex of the parent affected.

PMID- 21169073
TI  - [Alendronate treatment of osteoporosis secondary to Duchenne muscular dystrophy].
AB  - INTRODUCTION: Reduced mobility and glucocorticoids as adjunctive therapy causes
      osteoporosis in Duchenne muscular dystrophy. Alendronate has been used in
      childhood osteoporosis of other aetiologies with good results and no adverse
      effects. PATIENTS AND METHODS: Three patients with Duchenne dystrophy, symptoms
      of bone involvement (prior history of generalized bone pain and fractures) and
      bone mineral density (BMD) by dual-energy X-ray absorptiometry with Z-score <=-2
      SD. Treatment with oral alendronate was initiated (10mg/day). RESULTS: There was
      an increase in lumbar (L2-L4) BMD in all cases, with improvement of bone pain. No
      fractures and adverse effects were observed during follow up. CONCLUSION: Oral
      alendronate produces an increase in BMD in these patients, with good tolerance
      and no need for hospitalization, and so improves quality of life and reduces
      health care costs.

PMID- 21169074
TI  - [Oily orange diarrhoea. Fish-induced keriorrhoea].

PMID- 21169075
TI  - [Ages of sitting up and walking in preterm newborns less than 1,500 G with
      bronchopulmonary dysplasia].
AB  - INTRODUCTION: Adverse neurological events in very low birth weight (VLBW)
      children with bronchopulmonary dysplasia (BPD) are more frequent than in children
      without. An understanding of the ages when preterm infants acquire certain motor
      skills will give parents more appropriate information on motor development. The
      objective of the present study is to estimate the influence between BPD and the
      age of acquisition of sitting unsupported and independent walking in VLBW
      children with normal neurological examination at 2 years of corrected age.
      PATIENTS AND METHODS: A longitudinal study was conducted on a cohort of 885
      children with VLBW, admitted to the Hospital "12 de Octubre" between January 1991
      and December 2003. Age for both skills was established by interview with parents.
      Means were compared with t-test and Bonferroni adjustment where appropriate.
      RESULTS: Both motor skills were acquired later in the group with BPD (7.8+/-2m
      vs. 7.1+/-1.3m for sitting unsupported and 14.5+/-3.8m vs. 13.4+/-2.5m for
      walking) (P<.001). BPD was associated with delayed acquisition (above p90) of
      these skills, OR=2.6 (1.6-4.1) for sitting and OR=2.8 (1.6-4.8) for walking.
      Association was found after adjusting for gestational age (GA) and weight.
      CONCLUSION: BPD was associated with delayed acquisition of both skills in VLBW
      children with normal neurological examination at 2 years.

PMID- 21169076
TI  - [Prediction of PaO2/FiO2 ratio from SpO2/FiO2 ratio adjusted by transcutaneous
      CO2 measurement in critically ill children].
AB  - OBJECTIVE: To evaluate if the inclusion of the transcutaneous CO(2) tension
      measurement (PtcCO(2)) can improve partial pressure of oxygen/ fraction of
      inspired oxygen ratio [PaO(2)/FiO(2) (P/F)] prediction from pulse oximetry
      saturation/FiO(2) ratio [SpO(2)/FiO(2) (S/F)]. METHODS: Retrospective analysis of
      blood gas data from critically ill children. PaO(2), SpO(2), FiO(2) and PtcCO(2)
      from 40 samples in 8 patients were analysed. A multiple linear regression model
      was performed to predict P/F ratio from S/F ratio and PtcCO(2). Using the
      equation obtained, S/F ratio values were calculated for P/F ratios of 200 and 300
      and different levels of PtcCO2. Receiver Operator Characteristic (ROC) curves
      were made to analyse the diagnostic values of P/F ratio (200 and 300). RESULTS:
      The linear regression model was: P/F=37.277+(1.072*S/F) - (1.567*PtcCO2);
      P<.0001; R(2)=0.469. Using the equation, for a PtcCO(2) value of 40 mmHg, P/F
      ratios of 200 and 300 corresponded to S/F ratios of 295.1 and 426.5,
      respectively. Computed P/F ratio less than 256.7 had 84.6% sensitivity and 85.2%
      specificity for the diagnosis of P/F ratio less than 200. Computed P/F ratio less
      than 297.6 had 89.7% sensitivity and 82% specificity for the diagnosis of P/F
      ratio less than 300. CONCLUSION: PtcCO(2) has a significant influence on the
      prediction of P/F ratio from S/F ratio. Prospective studies with more patients
      are needed to validate these results.

PMID- 21169077
TI  - HOSTILE: a mnemonic for factors affecting hand infection outcome.

PMID- 21169078
TI  - [Early stages of nephrology in Toulouse].
AB  - The story of nephrology in Toulouse is explained by Professor Jean-Michel Suc.
      From the 1950s until now, the understanding of renal physiology and kidney
      diseases is detailed, as well as the growth of dialysis and kidney
      transplantation.

PMID- 21169079
TI  - A high-throughput multiplexed screening assay for optimizing serum-free
      differentiation protocols of human embryonic stem cells.
AB  - Serum-free differentiation protocols of human embryonic stem cells (hESCs) offer
      the ability to maximize reproducibility and to develop clinically applicable
      therapies. We developed a high-throughput, 96-well plate, four-color flow
      cytometry-based assay to optimize differentiation media cocktails and to screen a
      variety of conditions. We were able to differentiate hESCs to all three primary
      germ layers, screen for the effect of a range of activin A, BMP4, and VEGF
      concentrations on endoderm and mesoderm differentiation, and perform RNA
      interference (RNAi)-mediated knockdown of a reporter gene during differentiation.
      Cells were seeded in suspension culture and embryoid bodies were induced to
      differentiate to the three primary germ layers for 6 days. Endoderm (CXCR4(+)KDR(
      )), mesoderm (KDR(+)SSEA-3(-)), and ectoderm (SSEA-3(+)NCAM(+)) differentiation
      yields for H9 cells were 80 +/- 11, 78 +/- 7, and 41 +/- 9%, respectively. Germ
      layer identities were confirmed by quantitative PCR. Activin A, BMP4, and bFGF
      drove differentiation, with increasing concentrations of activin A inducing
      higher endoderm yields and increasing BMP4 inducing higher mesoderm yields. VEGF
      drove lateral mesoderm differentiation. RNAi-mediated knockdown of constitutively
      expressed red fluorescent protein did not affect endoderm differentiation. This
      assay facilitates the development of serum-free protocols for hESC
      differentiation to target lineages and creates a platform for screening small
      molecules or RNAi during ESC differentiation.

PMID- 21169080
TI  - Laxity measurements using stress radiography to assess anterior cruciate ligament
      tears.
AB  - INTRODUCTION: The clinical diagnosis of the anterior cruciate ligament (ACL) tear
      is based on demonstrating anterior subluxation of the tibia on the femur. In any
      of the following perspectives, diagnostic (cutoff value confirming rupture),
      prognostic (treatment efficacy), and therapeutic (laxity influencing the
      treatment), this laxity can be measured on stress X-rays. WORKING HYPOTHESIS: The
      diagnostic value of dynamic radiographs is low for ACL rupture. Passive
      Telos((r)) X-rays have better diagnostic value, better radiologic quality, and
      are easier to carry out than active Franklin-type X-rays. MATERIAL AND METHODS: A
      cohort of 112 patients (28 females, 84 males; mean age, 33.7 years [range, 18-72
      years]) with an indication for knee arthroscopy were studied prospectively.
      Before undergoing the arthroscopic treatment, two series of images of both knees
      were taken: one series of passive anterior drawer dynamic X-rays on a Telos((r))
      device at 250 N and a series of active anterior drawer dynamic X-rays according
      to Franklin (contraction of the quadriceps against 7 kg of weight at the ankle).
      The arthroscopic evaluation of the ACL (reference status) was compared to the
      anterior laxity measurements (absolute and differential) of each knee compartment
      (medial, lateral, and average) to determine the diagnostic value of the two
      radiological tests. RESULTS: We found 70 patients with an "arthroscopically
      ruptured ACL", 32 with an "arthroscopically healthy ACL", and 10 with a "partial
      rupture". The measurement of the anterior drawer values on the dynamic X-rays
      (active and passive) by two independent observers was reliable and reproducible
      (ICC>0.80), particularly when using the medial compartment (ICC=0.96) and the
      differential values eliminating the interobserver measurement error and
      interindividual laxity variations. In terms of X-ray technique, the active images
      were more frequently painful and the radiographic result showed less good quality
      than the Telos images. The anterior drawer values in the "healthy ACL" group were
      significantly less than in the "ruptured ACL" group for the Telos((r)) images,
      whether the measurements were absolute or differential. For the Franklin images,
      this difference was only significant for the absolute values. Used for diagnosis
      (4-mm differential on the medial compartment), the passive dynamic images had
      lower diagnostic values (Se=59% and Sp=90%) than the series reported in the
      literature, which were marked by great heterogeneity. CONCLUSION: The measurement
      of anterior drawer values on Telos((r)) and Franklin dynamic X-rays is a reliable
      and reproducible measurement, particularly when using the medial compartment and
      differential measurements. This small series did not demonstrate a diagnostic
      value for the Franklin images, contrary to the Telos((r)) X-rays. Used for
      diagnostic purposes, the Telos((r)) images had a low sensitivity; consequently,
      they should be used preferentially for prognostic or therapeutic purposes. LEVEL
      OF EVIDENCE: Level III, prospective case-control study.

PMID- 21169081
TI  - [Message of the General Director of the Instituto Nacional de Cardiologia Ignacio
      Chavez on the 80th anniversary of the journal Archivos de Cardiologia de Mexico].

PMID- 21169082
TI  - [Special issue to commemorate the 80th anniversary of Archivos de Cardiologia de
      Mexico].

PMID- 21169083
TI  - [The brilliant course of Archivos de Cardiologia de Mexico].

PMID- 21169084
TI  - [Evidence-based cardiology: practical applications of clinical epidemiology].

PMID- 21169085
TI  - [Cardiac metabolism and perfusion evaluation in a rat model using 18F- FDG, 1-11C
      acetate, 13NH3 and micro-positron emission tomography (microPET)].
AB  - OBJECTIVE: To standardize an acquisition protocol for the study of myocardial
      glucolitic and oxidative metabolism and perfusion in a rat model. METHODS:
      Studies were carried out with the three main radiopharmaceuticals used to assess
      heart function:[18F]-FDG for glucolitic metabolism; [1-11C]-acetate for oxidative
      metabolism and [13N]-NH3for myocardial perfusion.[18F]-FDG -Five Wistar adult
      male rats were studied in three different protocols: non-fasting group, fasting
      group,8 h before the study with water provided ad libitum, and a fasting group by
      the same time receiving an oral 50%-glucose solution. Thirty-minute scans were
      performed with a microPET Focus 120, 30 and 60 min after the administration of
      370 - 555 MBq 18F-FDG. [1-11C]-Acetate -Eight rats were studied. Four static and
      four dynamic 30 min acquisitions after a 370 - 555 MBq of [1-11C]-acetate caudal
      vein administration.[13N]-NH3-Ten static studies were acquired 15 min post
      administration of 370- 555 MBq of 13NH3 isofluorane anesthesia. Comparative and
      visual analyses wy performer by two experts in the field. A semi-quantitative
      analysis was performa using 3D reconstructions and ROI selections with AMIDE
      software. RESULTS: The best images were those obtained from the non-fasting
      group, especially those taken at 60 min after the [18F]-FDG administration. High
      quality myocardial, static images were obtained with [1-11C]-acetate, and the
      dynamic adquisitions allowed the identification of myocardial perfusion. The
      13NH3images showed a homogeneous distribution of the radiotracer in different
      segments of the short, long and horizontal axes in the left ventricle.
      CONCLUSIONS: It is possible to standardize the microPET acquisition protocols for
      the three main radiopharmaceuticals to evaluate the heart function in a rat
      model. It is feasible to establish a valid protocol for measuring glucolitic and
      oxidative myocardial metabolism and perfusion for gene, drug or surgical therapy
      assessment.

PMID- 21169086
TI  - [Morbidity and hospital cost reduction in cardiac surgery using a presurgery
      ambulatory strategy].
AB  - In our hospital, the patients that need an elective cardiac surgery are admitted
      through the admission department on the basis of a waiting list. Since 1999, a
      fast track to hospitalization program has existed in the National Institute of
      Cardiology Ignacio Chavez for patients with low surgical risk. Later, in 2004,
      this program was extended to patients to moderate risk, based on rules accepted
      worldwide, and our own experience. OBJECTIVES: 1) To compare two ways of
      admission that are used currently: fast track to hospitalization, against
      admission department waiting list. We compared major events: death or events that
      increased the hospital stay by more than 14 days (infections, alterations of
      rhythm and conduction, reoperations and others), 2) To compare the days of
      hospitalization and money spent by the hospital. METHODS: We conformed 2 groups
      of 347 patients. The admission department waiting list group was admitted before
      doing their preoperative studies, which is the customary form for hospitalization
      by our admissions department, while the group of fast track to hospitalization
      was obligated to have their laboratory exams complete and any other diseases
      resolved or controlled previously. The monetary cost per patient for the hospital
      was calculated based on the patient's socioeconomic classification. STATISTICAL
      ANALYSIS: Student t test was conduncted on independent samples and numerical
      variables, and Chi square for categorical variables. We considered a p <0.05 to
      be statistically significant. RESULTS: In average in both groups, 75% underwent
      valve operation and 25% underwent congenital heart disease repair, 49% were
      women, age 47 15 years. The comparison between the groups fast track to
      hospitalization and admission department waiting list group were: Mortality: 4.3%
      vs. 5.8% (p=0.38). Major events that needed a hospital stay of more than 14 days:
      73 vs. 97 cases respectively (p = 0.032). Infections: 22 vs. 29 (p = 0.14).
      Mediastinitis: 2 vs. 9 respectively (p = 0.033). In-hospital stay: were 11 days
      vs. 20 days (p = 0.0001), the biggest difference was found in the pre-surgical
      time: 2 vs. 9 days respectively (p = 0.0001). CONCLUSION: The postoperative
      morbidity in general was lower in fast track to hospitalization group, and the
      mediastinitis showed a decrease with statistical significance. The time interval
      between hospital admission an operation in fast track to hospitalization group
      was significantly shorter. We believe that the decrease in the exposure time to
      nosocomial pathogens present in the hospital environment was directly related to
      the low number of mediastinitis. Finally, the decrease in time of hospital stay
      represented a 32% monetary savings for the hospital.

PMID- 21169087
TI  - [PET evaluation of inflammatory process in Takayasu's arteritis].
AB  - OBJECTIVE: To determine the application of PET in monitoring patients with
      Takayasu's arteritis (TA) with Inflammatory activiti (IA) and this correlation
      with established clnical criteria. METHODS: 35 patients diagnosed with TA were
      enrolled. Determination of erythrocyte sedimentation rate, C -reactive protein,
      fibrinogen and a complete blood count was performed and clinical criteria of
      activity were applied. A baseline PET was performed in all patients. Those who
      were positive for IA received drug treatment. Among the group of active patients,
      ten were randomized to undergo another PET scan and clinical criteria
      determination to evaluate inflammatory activity after 6 months of treatment. We
      compared clinical criteria with PET capacity to determine IA. The results between
      the initial and final PET were finally compared. RESULTS: Clinical criteria had a
      sensitvity of 63% and a specificity of 90% to show IA. Sensivity decreased after
      6 months of treatment to 27%. DISCUSSION: This is the first prospective study
      that compares the findings of PET before and after treatment for IA in patients
      with TA. Clinical criteria lack sensitivity for the detection of IA in the follow
      up after treatment. CONCLUSIONS: PET is a diagnostic technique with high
      sensitivity and specificity for the diagnosis and monitoring of patients with TA
      and inflammatory activity.

PMID- 21169088
TI  - [Coronary heart disease morbidity and mortality trends at the Instituto Mexicano
      del Seguro Social. An ecological study of trends].
AB  - OBJECTIVE: To analyze secular trends of coronary heart disease morbidity and
      mortality in Mexicans protected by the Mexican Institute of Social Security.
      METHODS: An ecological trend analysis study was conducted on coronary heart
      disease morbidity and mortality in the Mexican population protected by the
      Institute. All deaths were adjusted for miscoding and misclasification and rates
      were age - adjusted according to the age distribution proposed by the World
      Health Organization. Hospital discharges, as well as the number of patients
      seeking medical care for coronary heart disease, were analyzed as an indirect
      incidence measure. Fatality rates and the mean number of hospitalization days
      were also estimated. RESULTS: Coronary heart disease mortality has shown a stable
      trend at the end of last century and a descending trend in the in the first year
      of this century, both in males (r=0.84;r2=0.70; p <0.001) as in females (r = 
      0.76; r2 =0.57; p <0.001). There is an age-effect on mortality; mortality is
      higher in males, mainly at younger ages (male-female rate = 3.44). Fatality rates
      have progressively decreased and the mean age of death has increased by four
      years in the last two decades. CONCLUSIONS: The stable trend and later descent on
      coronary heart disease mortality may be best explained by an increase in the
      quality of health care and secondary prevention. Nevertheless, there is a need to
      strengthen primary prevention by modifying exposure to major cardiovascular risk
      factors in Mexicans.

PMID- 21169089
TI  - [Importance of the heart-brain binomial in the management of congenital heart
      disease].
AB  - A case of a two month infant with complex congenital heart disease (aortic
      coarctation with ventricular septal defect) associated to a cellular brain
      migration failure is presented. The management strategy consisted on the
      correction of congenital heart disease by means of a two-stage surgery without a
      further preoperative evaluation of the neurological status. The patient developed
      several perioperative complications such as two episodes of cardiac arrest,
      reconnection to cardiopulmonary bypass, cardiac tamponade, chilothorax and septic
      shock. A neurological protocol consisting in electroencephalography, brain
      magnetic resonance and Single Photon Emission Computed Tomography (SPECT) was
      practiced during the postoperative period, which detected microgyria with
      paquigyria and a cellular brain migration failure was suspected. The final
      outcome was death due to multisystemic failure and the autopsy confirmed the
      neurological disease, as well as poor life function prognosis. Should the heart
      brain binomial had been considered in an integral preoperative evaluation, the
      therapeutical approach could have been modified.

PMID- 21169090
TI  - [Medical reflections on a case of pulmonary thromboembolism in pregnancy].
AB  - Maternal mortality is still high in the world. Pulmonary thromboembolism as a
      cause of death is the second in developed countries. The frequency of reported
      events in Latin-American is 0.6%, which contrasts with that reported for
      developed countries (14.9%). This difference may be related to information bias.
      A review of the current information about this topic is presented, and we report
      a short case of a pregnant woman who presented pulmonary thromboembolism event at
      30 weeks of pregnancy. Appropriate therapy allowed maternal and fetal survival.

PMID- 21169091
TI  - [Science, health and education: a priority and a model].
AB  - Myocardial infarction and brain infarction are personally dramatic events.
      However, these cardiovascular events are also globally dramatic not just for
      being the first cause of death all over the world. In addition, their prevalence
      is increasing and the high economic cost of treatment - technological and
      pharmacological - is already inaccessible in many regions of the world. In light
      of the above, we have established an international foundation under the priority
      concept "Science, Health and Education" (SHE). This fundation is based in a new
      Spanish research and funding model, the "Nacional Cardiovascular Research Center
      (CNIC). The research aspect is geared towards promoting cardiovascular health and
      disease management both individually and among the population. Funding is public
      and private, excluding the fharmaceutical industry, wich thus prevents conflicts
      of interest. In the cardiovascular setting, the entity SHE as conceptual
      priority, and the CNIC as Scientific basis or model can be pilot or applicable to
      other health and disease issues in general.

PMID- 21169092
TI  - [A critical review of the "peer review" process].
AB  - The main objective of biomedical journals is to publish high-quality scientific
      studies and to ensure a widespread dissemination of their contents, Journals
      compete for the best science generated in their respective disciplines and,
      therefore, they critically scrutinize the scientific quality of all submitted
      papers in order to identify and select only those thar merit publication. The
      "peer review" system represents the cornerstone of the scientific process. It
      provides a critical appraisal, by external independent experts, of the studies
      under consideration. The system is intended to improve the quality of the
      submitted papers but also to help the Editors in their decision-making process.
      The process has been widely embraced by the scientific and editorial
      onternational community but it is not free from caveats. In fact, although
      several strategies have been implemented to improve its quality and the results
      obtained, limitations still persist. Accordingly, its quality should be closely
      monitored to ensure excellence, limited scientific information exists on its real
      value. In this review we will critically analyze the "peer review" process and we
      will advance some ideas that may help to understand why, in spite of its
      limitations, it remains the "gold standar" for the selection of scientific
      manuscripts by biomedical journals.

PMID- 21169093
TI  - Catheter cryoablation of atrio-ventricular nodal reentrant tachycardia. A
      clinical review.
AB  - Cryoablation is a new method in interventional cardiac electrophysiology for
      percutaneous catheter ablation of cardiac arrhythmias. Cryothermal mapping
      enables the functional assessment of a particular site before permanent ablation.
      In this way, the targeted tissue may be confirmed as safe for ablation. This is
      useful in high risk ablation, for example, nex to the His bundle or the compact
      AV node. In the last decade, several studies have been addressed to AV-nodal
      reentry tachycardia (AVNRT) cryoablation. Current experiences indicate that
      cryoablation for AV-nodal reentry tachycardia is effective and safe. However, its
      wide use seems to be somewhat limited by a slightly lower efficacy when compared
      to radiofrequency. Further studies evaluating long-term success of cryothermal
      ablation versus radiofrequency are warranted. However, for high-risk ablations,
      cryoenergy is very helpful and should be systematically used. This article is a
      review of acute and long-term effects of cryoablation in patients suffering of AV
      nodal reentry tachycardia episodes.

PMID- 21169094
TI  - Cardiac resynchronization therapy: evaluation of ventricular dysynchrony and
      patient selection.
AB  - Cardiac resynchronization therapy (CRT) is an established treatment modality for
      systolic heart failure. Aimed to produce simultaneous biventricular stimulation
      and correct the lack of ventricular synchrony in selected patients with
      congestive heart failure, CRT has shown to improve mortality and reduce hospital
      admissions when compared to medical treatment. At present, the indication
      criteria for the implantation of a CRT device include an ejection fraction of
      less than 35%, heart failure symptoms consistent with NYHA functional class III
      IV and a QRS complex duration equal or longer than 120 milliseconds. It has been
      reported that 30% of patients who meet those criteria still may not derive
      clinical benefit from CRT. Due to the existing diversity of imagin modalities and
      resources for their process and analysis, a great expectation in terms of more
      accurate diagnosis of ventricular dyssynchrony has been raised. Reilable
      identification of dyssynchrony could allow us to better predict the favorable
      response of an individual patient to CRT and therefore offer this procedure to
      those individuals most likely to benefit. We review the available techniques for
      the study of ventricular dyssynchrony for CRT patient selection and the results
      of its application in clinical trials. Despite tremendous progress in the imaging
      technology available for the assessment and diagnosis of ventricular
      dyssynchrony, an ideal method has not been identified and the duration of QRS
      complex in the surface ECG remains the accepted criteria of dyssynchrony in the
      selection of patients for CRT.

PMID- 21169096
TI  - [Nonsense in medical papers written in Spanish].

PMID- 21169097
TI  - [Smoking. The natural cause asks for respect].
AB  - Smoking is responsible for atherosclerosis-mediated cardiovascular pandemic.
      Change and accelerate reactions in structures and functions. Form factors and
      stimulates tumor atheroma. Induces thrombosis and occludes arteries. The sinister
      intrusion attacks the cardiovascular system. The damage occurs in their genetic
      foundations and bimolecular intimacy. The remedy is abstinence, solves everything
      and it is just behavior. Addiction feeds dissent that is based on fallacies and
      irrelevant controversies. Much is ignorance, misjudgments, bad experiences which
      originates controversies. Why are things this way? it is not understood as it
      should. Public opinion is manipulated information, reductionism and negative
      Manichaeism. The solutions are provided through interdisciplinary and holistic
      reasoning. They suggest sticking to education based on universal values from
      early ages. Also abstinence promotion and self-control culture, for the sake of
      oneself and towards neighborhood. The new paradigm should pursue a doctrine of
      conversion, which nobody is exempt from benefit. Interpreting the alternative
      posed by nature of stating Phyisiodulia or Physiopathology is equivalent to:
      respect, or illness and death.

PMID- 21169095
TI  - Ionic and substrate mechanism of atrial fibrillation: rotors and the exitacion
      frequency approach.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in
      humans, however its mechanisms are poorly understood and its therapy is often sub
      optimal. This article reviews recent experimental, numerical and clinical data on
      dynamics of wave propagation during AF and its mechanistic link to ionic and
      structural properties of the atria. At the onset, the article presents numerical
      and optical mapping data suggesting that a presence of periodic source with
      increasingly high dominant frequency (DF) of excitation underlies observations of
      dispersion of local activation rate during AF. Further optical mapping studies in
      isolated normal sheep hearts in the presence of acetylcholine (ACh) reveals that
      rotors localized to the left atrium (LA) drive the arrhythmia and are faster than
      those in the right atrium (RA). Patch-clamp data from isolated cardiomycytes
      shows that the ACh-modulated potassium inward rectifier current is higher in the
      LA than in the RA which may explain the higher DFs and sensitivity of LA rotors
      to ACh compared with RA rotors. Following, the role of fibrosis in governing the
      propagation dynamics with a decrease in excitation frequency is presented in AF
      in failing sheep hearts and complex activation in cell cultures. Translation into
      the clinical setting is then discussed: DF distribution in patients with
      paroxysmal AF follows the LA-to-RA gradients found in the acute cholinergic AF of
      sheep hearts with highest DFs localized primarily to the posterior LA wall and
      pulmonary veins (PV) region; however in patients with persistent AF, the highest
      DFs localize mainly outside of the PVs region with possible implication on the
      outcome of ablation procedures. Next, intravenous injection of adenosine to
      patients in AF is demonstrated to result in further acceleration of high DF sites
      and suggests that reentrant activity, rather than triggered or automatic
      activity, maintains the arrhythmia. Finally, analysis of excitation during AF
      developed in patients post-cardiac surgery suggests a DF distribution similar to
      that of patients with paroxysmal AF with dependency on fibrosis as found in sheep
      failing hearts and cell cultures. In sum, the article presents data demonstrating
      the use of DF of excitation in linking wave propagation mechanisms to ionic and
      structural properties in both experimental and human AF.

PMID- 21169098
TI  - [Mirowski, his cardiological training at the Instituto Nacional de Cardiologia
      Ignacio Chavez and the implantable cardioverter defibrillator].

PMID- 21169099
TI  - Contributions of the Instituto Nacional de Cardiologia in the diagnosis and
      treatment of the Wolff-Parkinson - White syndrome.
AB  - Since the first description of the disease now known as Wolff-Parkinson-White
      syndrome, much knowledge has been gained through several experimental and
      clinical studies all over the world. The Instituto Nacional de Cardiologia
      Ignacio Chavez in Mexico City has not been the exception. In this report, we
      describe the clinical, electrocardiographic and electrophysiologic contributions
      of past and present researchers at the Institute, as well as the experience in
      the diagnosis and treatment of the W-P-W syndrome at this Instituto Nacional de
      Cardiologia Ignacio Chavez.

PMID- 21169100
TI  - [Some ethical dilemmas in the medical praxis].
AB  - We reviewed from a bioethical perspective and attempting prevention of potential
      conflicts derived communication failure during medical practice, palliative
      treatments and dignified death in the institutional practice as well as general
      practice; most of conflicts related to patient-doctor relationship could de
      prevented. We propose an attitude and aptitude plus in deep knowledge of patient,
      family, friends and legal representatives in terms fully honest communication to
      prevent most of conflicts and avoid its consequences against doctors and other
      health workers. Prevention is better and it depends of knowledge of norms, laws,
      general beliefs and common sense in this country and maybe others.

PMID- 21169101
TI  - [Mechanical circulatory supports. Advanced stage of heart failure].
AB  - Heart failure is considering one of the most prevalent diseases in recent years.
      Despite advances in the treatment with new drugs and devices such as implantable
      defibrillator and cardiac resynchronization therapy, the progression in heart
      failure leads to deterioration in the quality of life, frequent hospitalizations
      and high mortality rates. Advanced stage of this disease remains heart
      transplantation for treatment choice, although is not the adequate therapy for
      all the patients. Many of them require support with inotropic drugs, which lead
      to a progressive deterioration and limited survival, because waiting times are
      prolonged or transplantation is not performed. Therefore, progress in circulatory
      support devices allow to consider these as the treatment while awaiting
      transplantation and an alternative when the transplant is not considered an
      option. It is our objective to review the progress and the usefulness of
      circulatory support devices in patients with advanced heart failure, in which the
      last option is heart transplantation.

PMID- 21169102
TI  - [Usefulness of chewing gum for the resolution of postoperative ileus in left
      colon resections].
AB  - BACKGROUND AND AIM: Disturbances in intestinal motility have been described since
      XIX century, with a not very well understood pathogenesis and few therapeutic
      approaches. Considering chewing as an important stimulus to promote intestinal
      motility we designed this study to assess the efficacy of chewing gum to improve
      the postoperative ileus, and the clinical relevance of this intervention.
      METHODS: Were included patients who underwent for elective left hemicolectomy
      during January 2007 to December 2008. The patients were randomly assigned to
      receive chewing gum or nothing during the post-surgery period. The main outcomes
      assessed were duration of postoperative ileus, and reduction in hospitalization
      days. RESULTS: During the period of the study were included 32 patients, were
      included mainly men (11 and 9 in treated and control patients, respectively). The
      first defecation after surgery procedure occurs at (44.2 +/- 17.6 h) in the
      treated group and (55.5 +/- 14.8 h) in the control group (p = 0.05). In the same
      way oral tolerance was achieved faster in the treated group (p= 0.05). The
      hospital stay duration was not different among treated and not treated patients.
      CONCLUSIONS: The use of chewing gum in patients after elective left
      hemicolectomy, reduce the duration of the postoperative ileus. However, this does
      not reduce the hospital stay duration.

PMID- 21169103
TI  - [Level of satisfaction from patients who undergone an endoscopic procedure and
      related factors].
AB  - BACKGROUND: Patient satisfaction is a cognitive and emotional evaluation of the
      patient on the performance of health staff and is based on relevant aspects of
      their experience in health care. AIM: To determine the satisfaction level of
      patients after an endoscopic procedure in the gastrointestinal endoscopy service
      Specialty Hospital National Medical Center La Raza and to evaluate associated
      factors. MATERIAL AND METHODS: A modified and validated questionnaire was applied
      to assess patient satisfaction after an endoscopic procedure (mGHAA-9) in
      patients who underwent a gastroscopy or colonoscopy. Factors that influenced
      patient satisfaction were assessed. RESULTS: Two-hundred questionnaires were
      applied (response rate: 89.5%), in 62 men (34.6%) and 117 women (65.4%). Mean
      patient age was 51.3 years. The average score for the overall group was 30.9
      (maximum score of 35). In the overall assessment of satisfaction patients
      reported 60.9% excellent, very good 29.6%, good 8.9% and 0.6% regular. Factors
      that influenced patient satisfaction were: waiting time for appointment (OR
      3.104), explaining and answering questions (OR 2.961) and waiting time for
      performing the procedure (OR 2.408) Some factors did not influence on patient
      satisfaction: Sex: Male 58.1%, female 62.4% (p = 0.63), age 52 vs. 50 years (p =
      0.48) and sedation 64.7% vs. 60.5% (p = 0.8) CONCLUSIONS: The level of
      satisfaction of patients undergoing a gastroscopy or colonoscopy is good. The
      factors that influence the satisfaction of these patients are related to
      communication between doctor and patient, and waiting time for the study.

PMID- 21169104
TI  - [Endoscopic inanimate biological simulators for training in endoscopic mucosal
      dissection].
AB  - BACKGROUND: Simulators have been used as a training method; they allow training,
      skill development, standardization of techniques and the performance of a greater
      number of risk-free procedures. Endoscopic submucosal dissection (ESD) is the
      standard treatment for early gastric cancer since it allows en bloc resection of
      larger lesions however requires longer procedure time and has more complications
      than endoscopic mucosal resection. OBJECTIVE: To evaluate the use of biological
      inanimate simulators in endoscopic training for the development of skills
      required for ESD. METHODS: Experimental design using a biological inanimate
      simulator to evaluate the development of endoscopic skills. Five trained
      endoscopists with knowledge of the ESD technique, but without previous experience
      were selected. Technical success, complication rate and procedure time were
      evaluated. Each participant performed a self-evaluation. RESULTS: 18 lesions of
      10-20 mm in diameter were dissected, with a mean area of 2.64 +/- 2 cm2 and a
      mean procedure time of 21.08 +/- 14.01 minutes (5.48 - 48.61). Self-evaluation
      and instructor's evaluation showed a strong positive correlation. There was no
      correlation between lesion size and procedure time. There was one perforation
      (5.8%), which was successfully managed with one endoclip. Complications such as
      bleeding could not be assed. CONCLUSIONS: The use of inanimate biological
      simulators allows training in complex endoscopic procedures such as ESD with a
      wide safety margin. Lesion size did not correlate with procedure time. It is
      necessary to increase the number of procedures to improve the learning curve.
      This simulator does not allow evaluation of complications other than
      perforations.

PMID- 21169105
TI  - [Evaluation of non-invasive fibrosis indices in Mexican patients with chronic
      hepatitis C].
AB  - BACKGROUND: Among the many methods proposed to predict the presence of fibrosis
      in patients with chronic hepatitis C are the indices models obtained from serum
      biochemical tests, the aspartate aminotransferase-toplatelet ratio index (APRI)
      and the Forns index (FI). OBJECTIVE: To compare the diagnostic accuracy of the
      Forns index and APRI for predicting cirrhosis. METHODS: We included 105 patients
      with chronic hepatitis C and a liver biopsy. The FI and APRI were calculated from
      the biochemical tests of each patient. Receivers operating characteristic (ROC)
      curves were calculated to determine the best cutoff to discriminate between
      cirrhosis (F4), advanced fibrosis (F3-F4), and portal fibrosis (F1) according to
      the Knodell score. Diagnostic accuracy was assessed by obtaining sensitivity
      (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive
      value (NPV) for each of the indices. RESULTS: ROC curves showed that the best
      cutoff for predicting cirrhosis (F4) for the FI is >7.64, with Sn 62.5% and Sp
      91.8% (Area under the curve, AUC = 0.881), for advanced fibrosis (F3 - F4) the
      best cutoff value is >6.93 with Sn 42.9% and Sp 89.6% (AUC = 0.772). An APRI
      value of >1.74 was the best predictor for F4 with Sn 75% and Sp 82% (AUC =
      0.799), and a cutoff value of >1.7 for predicting F3-F4 with Sn 47.6% and Sp
      85.4% (AUC = 0.768). CONCLUSIONS: The results confirm the utility of both the FI
      and APRI for predicting advanced fibrosis and cirrhosis.

PMID- 21169106
TI  - Capsaicin induction of esophageal symptoms in different phenotypes of
      gastroesophageal reflux disease.
AB  - BACKGROUND: Type 1 vanilloid receptors (TRPV1) have been described on esophageal
      afferent sensitive neurons. Stimulation of TRPV1 receptors with capsaicin may
      induce heartburn. Capsaicin is the pungent component of chili and the most
      extensively studied TRPV1 agonist. OBJECTIVES: To investigate the effect of
      esophageal stimulation with intraesophageal capsaicin administration on induction
      of esophageal symptoms and on esophageal chemo-sensitization to acid in different
      gastroesophageal reflux disease (GERD) phenotypes. METHODS: Healthy volunteers
      and patients with GERD (non-erosive [NERD], erosive GERD [EE] and Barrett's
      esophagus [BE]) were prospectively studied. All subjects were randomized to
      receive either intraesophageal perfusion capsaicin or saline 0.9%. Thirty minutes
      after saline or capsaicin infusion an acid perfusion test of HCl was performed. A
      week later, a crossover phase with capsaicin versus saline was performed. Five
      symptoms were evaluated every 5 min during the first 30 minutes after capsaicin,
      saline, and acid perfusion: chest burning, chest pain, heartburn, epigastric
      burning, and epigastric pain. RESULTS: 17 healthy subjects and 31 GERD patients
      (10 NERD, 11 EE, and 10 BE) were included. Twenty- eight (90%) of GERD and 6
      (35%) of healthy subjects had esophageal symptoms after capsaicin perfusion. Mean
      for the 5 evaluated symptoms induced by capsaicin was significantly higher in the
      GERD group compared to the control group. The highest symptom severity was in the
      erosive subgroup. Capsaicin decreased the 5 symptoms induced by acid perfusion in
      both healthy volunteers and GERD patients. Total score of esophageal symptom
      severity (produced by acid perfusion) was significantly reduced by capsaicin
      infusion in the BE group. CONCLUSIONS: Capsaicin induces esophageal and gastric
      symptoms in healthy volunteers and GERD patients. Capsaicin reduces esophageal
      chemosensitivity to acid, especially in patients with BE.

PMID- 21169107
TI  - [Fructose intolerance in patients with irritable bowel syndrome: a case-control
      study].
AB  - INTRODUCTION: Recently it has been reported that prevalence of fructose
      intolerance (FI) in patients with functional gastrointestinal disorders range
      between 38% -75%. OBJECTIVE: To determine the prevalence of FI in subjects
      diagnosed with irritable bowel syndrome (IBS). METHODS: We studied 25 subjects
      (17 women, average age 36 years) with IBS (Rome II) and 25 healthy controls (14
      women, mean age 37 years) who underwent a breath test after oral loading with
      fructose (Gastrolyzer (r), Bedfont Scientific Ltd., UK). The load consisted of 25
      grams of fructose dissolved in 250 ml of water (10% solution). Breath test
      analysis of the particles per million (ppm) of hydrogen exhaled were performed
      every 15 minutes for 3 hours. The fructose breath test was considered positive
      when concentrations of hydrogen were higher than at 20 ppm or a raising greater
      than 5 ppm in 3 consecutive samples was detected. RESULTS: According to the Rome
      II criteria, 10 patients (40%) had IBS-C, 9 (36%) had IBS-D and 6 (24%) had IBS
      M. Thirteen (52%) of IBS patients had IF, while only 4 (16%) of control subjects
      (p = 0.01). Patients with IBS and fructose intolerante tend to suffering from
      diarrhea predominant IBS (p = 0.053). CONCLUSIONS: Fructose intolerance may be
      responsible for gastrointestinal symptoms in at least half of IBS patients,
      especially in the group of patients with IBS-D.

PMID- 21169108
TI  - [Differences between Chicago and traditional classifications in the diagnosis of
      esophageal motor disorders with high-resolution manometry and topography of
      esophageal pressure].
AB  - BACKGROUND: With the introduction of high resolution manometry (HRM) and
      esophageal topography a novel classification (Chicago Classification) has been
      proposed for the diagnosis of esophageal motor disorders (EMD). Clinical
      differences with the traditional classification are currently under evaluation.
      AIM: To investigate differences between the Chicago (CC) and traditional (TC)
      classifications in the diagnosis of EMD. METHODS: Consecutive patients with
      indication for esophageal manometry were studied. HRM was performed with a 36
      sensors solid-state catheter and Manoview software (V2.0).Conventional manometric
      tracings were analyzed by an investigator blinded to the results of HRM.
      Diagnosis by CC and CT were compared. RESULTS: Two hundred patients were studied,
      106 (53%) of them women (53%) with a mean patient age of 43.4 (range 16 - 84)
      years. Preoperative evaluation for GERD 152 (76%) was the most frequent
      indication. Achalasia (8), scleroderma (2) and peristaltic dysfunction (60 vs.
      59) were similarly diagnosed by CC and CT. Spastic disorders were more frequently
      identified by CC: nutcracker esophagus (NC) in 3, spastic NC in3 and segmental NC
      in 11 patients versus TC: NC 5. Three patients had spasm with CC and 1 with TC.
      Non specific motor disorder was diagnosed by TC and 2 patients had functional
      obstruction with CC. Hypotensive lower esophageal sphincter was identified in 63
      patients with CC vs.57 with TC. CONCLUSIONS: Spastic disorders and functional
      obstruction were the EMD better identified by HRM and CC.

PMID- 21169109
TI  - [External validity of a relevant model for Irritable Bowel Syndrome (IBS) using
      chronic stress by water avoidance in Wistar rats].
AB  - BACKGROUND: Development of animal models has been one of the most remarkable
      achievements for Irritable Bowel Syndrome (IBS) research. These models need to
      exhibit face validity, construct and predictive validity, as well as internal
      (replicability) and external validity (generalizability). Among these models,
      chronic stress induced by water avoidance exposure (WA) has been validated in
      rats through increasing visceral hypersensitivity, motility impairment, anxiety
      and, colonic immune activity, all related to IBS. OBJECTIVE: To assess the
      external validity of WA indirectly on colonic motility in Wistar rats. METHOD:
      Ten male-Wistar rats were exposed to WA and compared with ten Wistar rats not
      exposed (controls). At the end of each exposure, the quantity of fecal pellets
      were determined and considered as a sign of autonomic regulation of colonic
      motility. Data was analyzed with a general linear model for repeated measures.
      RESULTS: Rats exposed to WA had higher number or pellets than controls: 7.46 +/-
      0.45 (95%CI: 6.51, 8.41) vs. 2.88 +/- 0.45 (1.93, 3.83), p < 0.001. The higher
      number of pellets was related to WA exposure as there were no other significant
      interactions. In both groups, the number of pellets was higher during the first
      day and then decreased progressively. CONCLUSIONS: Chronic stress induced through
      WA in Wistar rats, exhibits external validity as an experimental model for IBS
      research and our findings of increased number of fecal pellets coincide with the
      appearance hypermotility related to IBS. The model is optimum for research
      studies on this disorder.

PMID- 21169110
TI  - [Prevalence and clinical characteristics of the IBS subtypes according to the
      Rome III criteria in patients from a clinical, multicentric trial. A report from
      the Mexican IBS Working Group].
AB  - BACKGROUND: In Mexico the prevalence of irritable bowel sindrome (IBS) using Rome
      II criteria varies between 16 and 35%. OBJECTIVE: To analyze the relative
      frequency of the IBS subtypes according to the Rome III criteria. METHODS: A
      multicentric study in 1677 IBS-Rome III patients that consulted private medical
      clinics. They all answered a structured interview by their physicians to
      determine the IBS subtype and to evaluate their symptoms intensity (Likert
      Scales). Patients self-evaluated their symptoms as well by using 10 cm visual
      analog scales for each one. RESULTS: Women represented 76.8% of the patients for
      a F:M ratio of 3.3:1. The relative frequencies of the IBS subtypes were IBS-M:
      48.4%, IBS-E: 43.0%, IBS-D: 5.6% and IBS-U: 2.8% with females predominating among
      all. However, IBS-D included 1.7 to 2.4 times more men than any of the other
      subtypes. The IBS-M reported a higher frequency and intensity of halitosis and
      vomiting and a higher intensity of burping; while those with IBS-E reported a
      higher frequency and intensity of straining and the IBS-D more urgency for a
      bowel movement, fecal incontinence and mucous in the stools. CONCLUSIONS: In IBS
      Rome III patients in Mexico, IBS-M is the most common subtype and is more
      commonly associated with dyspeptic symptoms while the IBS-E reported more outlet
      symptoms and the IBS-D fecal incontinence. There is a higher female predominance
      amongst all, however men are more likely to be in IBS-D.

PMID- 21169111
TI  - [Diagnosis of achalasia using high resolution esophageal manometry].

PMID- 21169112
TI  - [Diagnosis of pelvic floor dyssynergia using high resolution anorectal
      manometry].

PMID- 21169113
TI  - [Rome Foundation diagnostic algorithms for common gastrointestinal symptoms in
      Spanish].

PMID- 21169114
TI  - [An algorithmic approach to the diagnosis of functional gastrointestinal
      disorders].

PMID- 21169115
TI  - [Esophageal disorders].

PMID- 21169116
TI  - [Gastroduodenal disorders].

PMID- 21169117
TI  - [Disorders of gallbladder and sphincter of Oddi].

PMID- 21169118
TI  - [Functional abdominal pain syndrome: constant abdominal pain or frequently
      recurring].

PMID- 21169119
TI  - [Intestinal disorders].

PMID- 21169120
TI  - [Anorectal disorders].

PMID- 21169123
TI  - [Whipple's disease: a case report and review of the literature].
AB  - Whipple's disease is a systemic infectious condition caused by a gram-positive
      bacteria belonging to the family of actinomycetes called Tropherima whipplei. It
      presents most often in males and 13% of patients present with severe diarrhea,
      fever, adenopathy, weight loss and pigmentation of the skin. Diagnosis is made
      through duodenal biopsy by which shows foamy macrophages PAS positive. In cases
      where the histology is negative, we can make the identification of the infectious
      agent by polymerase-chain reaction (PCR). We describe a 47 years old woman with
      Whipple's disease whose diagnosis was made through the duodenum and colon
      biopsies showing infiltration by PAS-positive macrophages.

PMID- 21169124
TI  - [Oropharyngeal dysphagia as a first manifestation of dermatomyositis associated
      with colon cancer].
AB  - Dermatomyositis (DM) is an idiopathic inflammatory myopathy associated with
      characteristic skin manifestations. In 15-20% of patients present with dysphagia,
      it is associated with nutritional deficiency, predisposition to aspiration
      pneumonia, decreased quality of life and a poor prognosis. There is a well
      recognized association between DM and malignancies, including ovarian, breast,
      lung, and colon cancer. We report a case of a male patient aged 85 with DM
      associated with colon adenocarcinoma; progressive dysphagia was the first
      manifestation, and subsequently proximal muscle weakness and typical skin lesions
      were present. Given the clinical suspicion of DM as a paraneoplastic syndrome,
      tumor markers were order and a high carcinoembryonic antigen was found. A
      colonoscopy study and histopathologic examination revealed the presence of
      adenocarcinoma of the colon.

PMID- 21169125
TI  - Mitochondrial oxidative stress significantly influences atherogenic risk and
      cytokine-induced oxidant production.
AB  - BACKGROUND: Oxidative stress associated with cardiovascular disease (CVD) risk
      factors contributes to disease development. However, less is known whether
      specific subcellular components play a role in disease susceptibility. In this
      regard, it has been previously reported that vascular mitochondrial damage and
      dysfunction are associated with atherosclerosis. However, no studies have
      determined whether altered mitochondrial oxidant production directly influences
      atherogenic susceptibility and response in primary cells to atherogenic factors
      such as tumor necrosis factor-alpha (TNF-alpha). OBJECTIVES: We undertook this
      study to determine whether increased mitochondrial oxidant production affects
      atherosclerotic lesion development associated with CVD risk factor exposure and
      endothelial cell response to TNF-alpha. METHODS: We assessed atherosclerotic
      lesion formation, oxidant stress, and mitochondrial DNA damage in male
      apolipoprotein E (apoE)-null mice with normal and decreased levels of
      mitochondrial superoxide dismutase-2 (SOD2; apoE(-/-) and apoE(-/-), SOD2(+/-),
      respectively) exposed to environmental tobacco smoke or filtered air. RESULTS:
      Atherogenesis, oxidative stress, and mitochondrial damage were significantly
      higher in apoE(-/-), SOD2(+/-) mice than in apoE(-/-) controls. Furthermore,
      experiments with small interfering RNA in endothelial cells revealed that
      decreased SOD2 activity increased TNF-alpha-mediated cellular oxidant levels
      compared with controls. CONCLUSIONS: Endogenous mitochondrial oxidative stress is
      an important CVD risk factor that can modulate atherogenesis and cytokine-induced
      endothelial cell oxidant generation. Consequently, CVD risk factors that induce
      mitochondrial damage alter cellular response to endogenous atherogenic factors,
      increasing disease susceptibility.

PMID- 21169126
TI  - Effects of short-term exposure to inhalable particulate matter on telomere
      length, telomerase expression, and telomerase methylation in steel workers.
AB  - BACKGROUND: Shortened leukocyte telomere length (LTL) is a marker of
      cardiovascular risk that has been recently associated with long-term exposure to
      ambient particulate matter (PM). However, LTL is increased during acute
      inflammation and allows for rapid proliferation of inflammatory cells. Whether
      short-term exposure to proinflammatory exposures such as PM increases LTL has
      never been evaluated. OBJECTIVES: We investigated the effects of acute exposure
      to metal-rich PM on blood LTL, as well as molecular mechanisms contributing to
      LTL regulation in a group of steel workers with high PM exposure. METHODS: We
      measured LTL, as well as mRNA expression and promoter DNA methylation of the
      telomerase catalytic enzyme gene [human telomerase reverse transcriptase (hTERT)]
      in blood samples obtained from 63 steel workers on the first day of a workweek
      (baseline) and after 3 days of work (postexposure). RESULTS: LTL was
      significantly increased in postexposure (mean +/- SD, 1.43 +/- 0.51) compared
      with baseline samples (1.23 +/- 0.28, p-value < 0.001). Postexposure LTL was
      positively associated with PM10 (beta = 0.30, p-value = 0.002 for 90th vs. 10th
      percentile exposure) and PM1 (beta = 0.29, p-value = 0.042) exposure levels in
      regression models adjusting for multiple covariates. hTERT expression was lower
      in postexposure samples (1.31 +/- 0.75) than at baseline (1.68 +/- 0.86, p-value
      < 0.001), but the decrease in hTERT expression did not show a dose-response
      relationship with PM. We found no exposure-related differences in the methylation
      of any of the CpG sites investigated in the hTERT promoter. CONCLUSIONS: Short
      term exposure to PM caused a rapid increase in blood LTL. The LTL increase did
      not appear to be mediated by PM-related changes in hTERT expression and
      methylation.

PMID- 21169127
TI  - Survival analysis of long-term exposure to different sizes of airborne
      particulate matter and risk of infant mortality using a birth cohort in Seoul,
      Korea.
AB  - BACKGROUND: Several studies suggest that airborne particulate matter (PM) is
      associated with infant mortality; however, most focused on short-term exposure to
      larger particles. OBJECTIVES: We evaluated associations between long-term
      exposure to different sizes of particles [total suspended particles (TSP), PM <=
      10 MUm in aerodynamic diameter (PM10), <= 10-2.5 MUm (PM(10-2.5)), and <= 2.5 MUm
      (PM(2.5))] and infant mortality in a cohort in Seoul, Korea, 2004-2007. METHODS:
      The study includes 359,459 births with 225 deaths. We applied extended Cox
      proportional hazards modeling with time-dependent covariates to three mortality
      categories: all causes, respiratory, and sudden infant death syndrome (SIDS). We
      calculated exposures from birth to death (or end of eligibility for outcome at 1
      year of age) and pregnancy (gestation and each trimester) and treated exposures
      as time-dependent variables for subjects' exposure for each pollutant. We
      adjusted by sex, gestational length, season of birth, maternal age and
      educational level, and heat index. Each cause of death and exposure time frame
      was analyzed separately. RESULTS: We found a relationship between gestational
      exposures to PM and infant mortality from all causes or respiratory causes for
      normal-birth-weight infants. For total mortality (all causes), risks were 1.44
      (95% confidence interval, 1.06-1.97), 1.65 (1.18-2.31), 1.53 (1.22-1.90), and
      1.19 (0.83-1.70) per interquartile range increase in TSP, PM10, PM(2.5), and
      PM(10-2.5), respectively; for respiratory mortality, risks were 3.78 (1.18
      12.13), 6.20 (1.50-25.66), 3.15 (1.26-7.85), and 2.86 (0.76-10.85). For SIDS,
      risks were 0.92 (0.33-2.58), 1.15 (0.38-3.48), 1.42 (0.71-2.87), and 0.57 (0.16
      1.96), respectively. CONCLUSIONS: Our findings provide supportive evidence of an
      association of long-term exposure to PM air pollution with infant mortality.

PMID- 21169130
TI  - Plasma matrix metalloproteinase 9 correlates with disorders of brain magnesium
      homeostasis in patients undergoing coronary artery bypass surgery.
AB  - BACKGROUND: Changes in plasma matrix metalloproteinase 9 (MMP-9) concentrations
      and parallel changes in brain magnesium homeostasis have not been examined in
      cardiac surgery patients. The purpose of the present study was to analyse these
      relationships in patients undergoing coronary artery bypass surgery (CABG) with
      extracorporeal circulation (ECC). Additionally, the effect of volatile
      anaesthetics was considered. PATIENTS AND METHODS: Adult patients undergoing CABG
      with ECC under general anaesthesia were studied. Plasma MMP-9 and total (tMg) and
      ionized (iMg) magnesium concentrations were measured during surgery and during
      the early postoperative period. The plasma arteriovenous (a-v) tMg and iMg
      differences in the brain circulation were considered to be markers for brain
      magnesium homeostasis. The Mini-Mental State Examination test and computer
      tomography were used to diagnose postoperative neuropsychological disorders
      (PNPDs). RESULTS: In total, 92 patients were examined. PNPDs were noted in 17
      cases. Cardiac surgery resulted in increased plasma levels of MMP-9. The highest
      MMP-9 concentrations were observed in patients with PNPDs. MMP-9 concentrations
      strongly correlated with a-v tMg and a-v iMg differences. Compared with arterial
      measurements, venous tMg and iMg concentrations were higher during and
      immediately after surgery and lower during the early postoperative period. The
      most severe differences in a-v tMg and iMg were noted in patients with PNPDs.
      CONCLUSION: 1. Cardiac surgery resulted in an increase in plasma MMP-9
      concentrations. 2. This increase in MMP-9 was significantly greater in patients
      with PNPDs. 3. The plasma MMP-9 concentration was correlated with disorders of
      brain Mg homeostasis.

PMID- 21169129
TI  - Ambient PM2.5 exposure up-regulates the expression of costimulatory receptors on
      circulating monocytes in diabetic individuals.
AB  - BACKGROUND: Exposure of humans to air pollutants such as ozone and particulate
      matter (PM) may result in airway and systemic inflammation and altered immune
      function. One putative mechanism may be through modification of cell-surface
      costimulatory molecules. OBJECTIVES: We examined whether changes in expression of
      costimulatory molecules on circulating cells are associated with ambient levels
      of fine PM [aerodynamic diameter <= 2.5 MUm (PM2.5)] in a susceptible population
      of diabetic individuals. METHODS: Twenty subjects were studied for 4 consecutive
      days. Daily measurements of PM2.5 and meteorologic data were acquired on the
      rooftop of the exam site. Circulating cell-surface markers that mediate innate
      immune and inflammatory responses were assessed by flow cytometry on each day.
      Sensitivity analysis was conducted on glutathione S-transferase M1 (GSTM1)
      genotype, body mass index, and glycosylated hemoglobin A1c (HbA1c) levels to
      determine their role as effect modifiers. Data were analyzed using random effects
      models adjusting for season, weekday, and meteorology. RESULTS: We found
      significantly increased monocyte expression (mean fluorescent intensity) of CD80,
      CD40, CD86, HLA-DR, and CD23 per 10-MUg/m3 increase in PM2.5 at 2- to 4-day lag
      times after exposure. These findings were significantly higher in obese
      individuals, in individuals with HbA1c > 7%, and in participants who were GSTM1
      null. CONCLUSIONS: Exposure to PM2.5 can enhance antigen-presenting cell
      phenotypes on circulating cells, which may have consequences in the development
      of allergic or autoimmune diseases. These effects are amplified in diabetic
      individuals with characteristics that are associated with insulin resistance or
      with oxidative stress.

PMID- 21169131
TI  - Ordered mesoporous silicates as matrices for controlled release of drugs.
AB  - Interest in and thereby also development of ordered mesoporous silicates as drug
      delivery devices have grown immensely over the past few years. On hand selected
      cases from the literature, the power of such systems as delivery devices has been
      established. Specifically, it is shown how it is possible to enhance the release
      kinetics of poorly soluble drugs by embedding them in mesoporous silicates.
      Further critical factors governing the structure and release of the model drug
      itraconazole incorporated in an SBA-15 matrix are briefly reviewed. The
      possibility of functionalizing the surface of mesoporous matrices also under
      harsher conditions offers a broad platform for the design of stimuli-responsive
      drug release, including pH responsive systems and systems which respond to the
      presence of specific ions, reducing agents, magnetic field or UV light, whose
      efficiency and biocompatibility has been established in vitro.

PMID- 21169132
TI  - Genetic polymorphisms in diabetes: influence on therapy with oral antidiabetics.
AB  - Due to new genetic insights, etiologic classification of diabetes is under
      constant scrutiny. Hundreds, or even thousands, of genes are linked with type 2
      diabetes. Three common variants (Lys23 of KCNJ11, Pro12 of PPARG, and the T
      allele at rs7903146 of TCF7L2) have been shown to be predisposed to type 2
      diabetes mellitus across many large studies. Individually, each of these
      polymorphisms is only moderately predisposed to type 2 diabetes. On the other
      hand, monogenic forms of diabetes such as MODY and neonatal diabetes are
      characterized by unique clinical features and the possibility of applying a
      tailored treatment.Genetic polymorphisms in drug-metabolizing enzymes,
      transporters, receptors, and other drug targets have been linked to
      interindividual differences in the efficacy and toxicity of a number of
      medications. Mutations in genes important in drug absorption, distribution,
      metabolism and excretion (ADME) play a critical role in pharmacogenetics of
      diabetes.There are currently five major classes of oral pharmacological agents
      available to treat type 2 diabetes: sulfonylureas, meglitinides, metformin (a
      biguanide), thiazolidinediones, and alpha-glucosidase inhibitors. Other classes
      are also mentioned in literature.In this work, different types of genetic
      mutations (mutations of the gene for glucokinase, HNF 1alpha, HNF1beta and Kir6.2
      and SUR1 subunit of KATP channel, PPAR-gamma, OCT1 and OCT2, cytochromes, direct
      drug-receptor (KCNJ11), as well as the factors that influence the development of
      the disease (TCF7L2) and variants of genes that lead to hepatosteatosis caused by
      thiazolidinediones) and their influence on the response to therapy with oral
      antidiabetics will be reviewed.

PMID- 21169133
TI  - Development of a selective biopharmaceutical from Herpes simplex virus type 1
      glycoproteins E and I for blocking antibody mediated neutralization of oncolytic
      viruses.
AB  - Future cancer therapies will be molecular cures. They will correct, block or
      destroy cancer cells by targeting molecular changes that lead to carcinogenesis.
      Destroying cancer cells can be done using oncolytic viruses. By blocking antibody
      mediated neutralization of oncolytic viruses, Herpes simplex virus type 1
      glycoproteins E and I could be used in the adjuvant treatment of cancer for
      improving the chances of oncolytic viruses to kill cancer cells in vivo.

PMID- 21169134
TI  - Development and optimization of metoprolol succinate gastroretentive drug
      delivery system.
AB  - Metoprolol succinate (MS) gastroretentive (GR) controlled release system was
      formulated to increase gastric residence time leading to improved drug
      bioavailability. Box-Behnken model was followed using novel combinations of
      sodium alginate (SA), sodium carboxymethylcellulose (NaCMC), magnesium alumino
      metasilicate (MAS) as independent variables. Floating lag time (Flag), t25, t50,
      t75, diffusion exponent as dependent variables revealed that the amount of SA,
      NaCMC and MAS have a significant effect (p < 0.05) on t25, t50, t75 and Flag.
      MSGR tablets were prepared and evaluated for mass, thickness, hardness,
      friability, drug content and floating property. Tablets were studied for
      dissolution for 24 h and exhibited controlled release of MS with floating for 16
      h. The release profile of the optimized batch MS01 fitted first-order kinetics
      (R2 = 0.9868, n = 0.543), indicating non-Fickian diffusion or anomalous transport
      by diffusion and swelling.

PMID- 21169135
TI  - Silymarin-solid dispersions: characterization and influence of preparation
      methods on dissolution.
AB  - The influence of preparation methodology of silymarin solid dispersions using a
      hydrophilic polymer on the dissolution performance of silymarin was investigated.
      Silymarin solid dispersions were prepared using HPMC E 15LV by kneading, spray
      drying and co-precipitation methods and characterized by FTIR, DSC, XRPD and SEM.
      Dissolution profiles were compared by statistical and model independent methods.
      The FTIR and DSC studies revealed weak hydrogen bond formation between the drug
      and polymer, while XRPD and SEM confirmed the amorphous nature of the drug in co
      precipitated solid dispersion. Enhanced dissolution compared to pure drug was
      found in the following order: co-precipitation > spray drying > kneading
      methodology (p < 0.05). All preparation methods enhanced silymarin dissolution
      from solid dispersions of different characteristics. The co-precipitation method
      proved to be best and provided a stable amorphous solid dispersion with 2.5
      improved dissolution compared to the pure drug.

PMID- 21169136
TI  - Sensitive and selective spectrophotometric assay of doxycycline hyclate in
      pharmaceuticals using Folin-Ciocalteu reagent.
AB  - A spectrophotometric method for the determination of doxycycline (DOX) is
      described. The method is based on the formation of blue colored chromogen due to
      reduction of tungstate and/or molybdate in Folin-Ciocalteu (F-C) reagent by DOX
      in alkaline medium. The colored species has an absorption maximum at 770 nm and
      the system obeys Beer's law over the concentration range 0.75-12.0 MUg mL-1 DOX.
      The apparent molar absorptivity is 2.78 * 104 L mol-1 cm-1. The limit of
      quantification and detection values are reported to be 0.20 and 0.08 MUg mL-1,
      respectively. Over the linear range applicable, the accuracy and precision of the
      method were evaluated on intra-day and inter-day basis. The reported mean
      accuracy value was 101.0 +/- 1.7 %, the relative error was <= 2.7 % and the
      relative standard deviation was <= 2.5 %. Application of the proposed method to
      bulk powder and commercial pharmaceutical tablets is also presented. No
      significant difference was obtained between the results of the proposed method
      and the official BP method. The procedure described in this paper is simple,
      rapid, accurate and precise.

PMID- 21169137
TI  - Formulation and in vitro characterization of spray dried microspheres of
      amoxicillin.
AB  - The purpose of the present study was to design muco-adhesive chitosan
      microspheres containing amoxicillin. Chitosan microspheres with a small particle
      size and good sphericity were prepared by a spray-drying method followed by
      chemical treatment with a chemical crosslinking agent (glutaraldehyde).
      Parameters affecting the crosslinking extent of the crosslinking time and the
      concentration of the crosslinker agent. Crosslinked spray-dried chitosan
      microspheres were analyzed for their morphological aspects, particle size, drug
      entrapment efficiency, swelling percent and in vitro drug release. Batch M4 with
      a drug polymer ratio of 1:2, dissolved in minimum concentration of acetic acid
      solution treated with glutaraldehyde, was found to be optimal giving controlled
      drug release for 10 h. It was found that both the increase of glutaraldehyde
      concentration and crosslinking duration decreased the swelling capacity of
      chitosan microspheres. This could be directly correlated to drug release from the
      microspheres.

PMID- 21169138
TI  - Aceclofenac topical dosage forms: in vitro and in vivo characterization.
AB  - Aceclofenac is a new generation non-steroidal anti-inflammatory drug showing
      effective anti-inflammatory and analgesic properties. It is available in the form
      of tablets of 100 mg. Importance of aceclofenac as a NSAID has inspired
      development of topical dosage forms. This mode of administration may help avoid
      typical side effects associated with oral administration of NSAIDs, which have
      led to its withdrawal. Furthermore, aceclofenac topical dosage forms can be used
      as a supplement to oral therapy for better treatment of conditions such as
      arthritis. Ointments, creams, and gels containing 1% (m/m) aceclofenac have been
      prepared. They were tested for physical appearance, pH, spreadability,
      extrudability, drug content uniformity, in vitro diffusion and in vitro
      permeation. Gels prepared using Carbopol 940 (AF2, AF3) and macrogol bases (AF7)
      were selected after the analysis of the results. They were evaluated for acute
      skin irritancy, anti-inflammatory and analgesic effects using the carrageenan
      induced thermal hyperalgesia and paw edema method. AF2 was shown to be
      significantly (p < 0.05) more effective in inhibiting hyperalgesia associated
      with inflammation, compared to AF3 and AF7. Hence, AF2 may be suggested as an
      alternative to oral preparations.

PMID- 21169139
TI  - Antimicrobial activity of some synthesized glucopyranosyl-pyrimidine carbonitrile
      and fused pyrimidine systems.
AB  - 3-Amino-5-(4-chlorophenylamino)-4-cyanofuran-2-carboxamide (2) was used as the
      key molecule for preparation of various furopyrimidines 3-9 and formation of
      spiro-cycloalkane furopyrimidines 10, 11. Also, poly fused heterocyclic compounds
      13-17 were prepared from compound 2. The synthesized compounds were screened for
      their antimicrobial activity.

PMID- 21169140
TI  - A novel analytical approach for reducing the consumption of organic solvents in
      the charge transfer-based spectrophotometric analysis: application in the
      analysis of certain antihypertensive drugs.
AB  - The present study describes the development of a novel analytical approach that
      can reduce by 50-fold the consumption of organic solvents in the charge transfer
      (CT)-based spectrophotometric analysis. The proposed approach employed 96
      microwell assay plates for carrying out the reaction. The CT reaction between the
      electron-donating analyte and electron-accepting reagent was performed in
      microwells (200-MUL of organic solvent) and the color signals were measured with
      a microwell-plate reader. Optimum conditions for the proposed approach were
      established for two antihypertensive drugs, namely ramipril (RML) and lisinopril
      (LSL) as model compounds for the electron-donating analytes, and 2,3-dichloro-5,6
      dicyano-1,4-benzoquinone (DDQ) as a pi-electron acceptor. Under the optimum
      conditions, Beer's law was obeyed in the concentration range of 6-100 and 6-60
      MUg mL-1 for RML and LSL, respectively. The limits of detection were 0.97 and
      1.10 MUg mL-1 for RML and LSL, respectively. The precision of the methods was
      satisfactory; the values of relative standard deviations did not exceed 1.1 %.
      The proposed approach was successfully applied to the analysis of pharmaceutical
      dosage forms with good accuracy and precision. The results were comparable with
      those of the reported methods. The approach described herein is of great
      practical value in pharmaceutical analysis because it reduces the exposure of
      analysts to the toxic effects of organic solvents, lowers the analysis cost by 50
      fold, and it has a high throughput property. Although the approach was validated
      for RML and LSL, the same methodology could be used for any electron-donating
      analyte for which a CT-reaction can be performed.

PMID- 21169141
TI  - "Hybrid" approach for the treatment of aortic arch aneurysm.
AB  - BACKGROUND: High mortality and morbidity rates are associated with the
      conventional surgery for aortic arch aneurysm because of cardiopulmonary bypass
      and deep hypothermic circulatory arrest. In this report, we describe a "hybrid"
      treatment for aortic arch aneurysm that combines the surgical debranching
      procedure and the stenting technique. METHODS: A surgical bypass graft is created
      from the ascending aorta to every main branch of the aortic arch. Subsequently,
      an endovascular stent graft is deployed retrogradely through the femoral artery
      with the aid of digital subtraction angiography. RESULT: The patient was
      discharged on postoperative day 7. A computed tomography scan was routinely
      performed at 1 week postoperatively to confirm the good patency of all grafts and
      the stent. CONCLUSION: The feasibility and the benefit of the hybrid treatment
      for aortic arch aneurysm are confirmed.

PMID- 21169142
TI  - The effect of fenoldopam and dopexamine on cytokine and endotoxin release
      following on-pump coronary artery bypass grafting: a prospective randomized
      double-blind trial.
AB  - BACKGROUND: Surgical trauma, exposure to an external circuit, and reduced organ
      perfusion contribute to the systemic inflammatory response following
      cardiopulmonary bypass (CPB). Reduced splanchnic perfusion causes disruption of
      the gastrointestinal mucosal barrier and the release of endotoxins. Fenoldopam (a
      new dopamine 1 receptor agonist) has been shown to be a specific renosplanchnic
      vasodilator in animal and human studies. We studied the effects of fenoldopam on
      the systemic inflammatory response and the release of endotoxins after CPB and
      compared the results with those for dopexamine. METHODS: Our prospective
      randomized study included 42 consecutive patients with good to moderate left
      ventricular function who were to undergo elective or inpatient coronary artery
      bypass grafting. We used closed envelope method to randomize patients to receive
      0.2 MUg/kg per minute of fenoldopam (n = 14), 2 MUg/kg per minute of dopexamine
      (n = 14), or normal saline (n = 14). Patients received their respective
      treatments continuously from anesthesia induction until the end of the first 24
      postoperative hours. Interleukin 1beta (IL-1beta), IL-6, IL-8, IL-10, IL-12,
      tumor necrosis factor alpha, complement 3a (C3a), C4a, C5a, and endotoxins were
      measured during the perioperative period. Repeated-measures analysis of variance
      was used to evaluate the results for the timed samples. RESULTS: There were no
      statistical differences between the groups with respect to pre- and
      intraoperative variables. Release of C3a was attenuated in the fenoldopam group
      (P = .002), and release of IL-6 and IL-8 was attenuated in the postoperative
      period in the fenoldopam group (P = .012 and .015, respectively). The other
      interleukins showed no uniform release in any of the 3 groups. There were no
      statistically significant differences in serum endotoxin elevation between the 3
      groups. CONCLUSION: A partial attenuation in the inflammatory response is
      possible with fenoldopam infusion. The elevation in serum endotoxin levels was
      not affected by dopexamine or fenoldopam infusion.

PMID- 21169143
TI  - Intracardiac cavopulmonary connection in patients with univentricular heart using
      intra-atrial lateral tunnel and intra-atrial conduit techniques.
AB  - BACKGROUND: In this study, we analyzed the time course of hemodynamic efficiency
      and follow-up in Fontan candidates who underwent the bidirectional Glenn
      procedure for staged intracardiac cavopulmonary connection (ICPC). METHODS:
      Between 1991 and 2008, 52 patients with univentricular heart (mean age, 3.3
      years; range, 2-8 years; 27 female patients [51.9%]) underwent ICPC. The cardiac
      malformations were as follows: tricuspid atresia, 25 cases (48.0%); common
      ventricle, 16 cases (30.7%); and pulmonary atresia with intact ventricular
      septum, 11 cases (21.1%). The intracardiac cavopulmonary procedure was indicated
      for all 52 cases. In 42 patients (80.7%), an intra-atrial lateral tunnel was
      constructed with a bovine pericardium patch. In the last 10 consecutive cases
      (19.3%), we performed a modified surgical technique in which we implanted an
      intra-atrial corrugated bovine pericardium tube sutured around the superior and
      inferior vena cava ostium. In all cases, a 4-mm fenestration was made to reduce
      the intratunnel pressure. All 52 patients had previously undergone a Glenn
      operation. RESULTS: There were 2 hospital deaths (3.8%) and no recorded late
      deaths. During the follow-up, all patients were medicated with antiplatelet
      drugs. To evaluate the hemodynamic performance, we used Doppler echocardiography,
      computed tomography, and magnetic nuclear resonance studies. There were no
      prosthesis thromboses during this followup period. To evaluate cardiac
      arrhythmias, we conducted a Holter study. The last 10 patients with an intra
      atrial conduit (IAC) presented with sinus rhythm and no arrhythmias during the
      last 4 years. The 50 surviving patients (96.1%) have been followed up for 6 to
      204 months; all these patients are free of reoperation. CONCLUSION: The Glenn
      operation, which is performed at an early age, prepares the pulmonary bed to
      receive the ICPC. The midterm results of the intracardiac Fontan procedure seem
      to be good. The modified surgical procedure (IAC) can be a good alternative
      technique to the Fontan procedure in suitable patients.

PMID- 21169144
TI  - Isolated unilateral pulmonary vein atresia in adult patients: a case report and
      literature review.
AB  - Unilateral pulmonary vein atresia is a rare abnormality that usually presents in
      infants with recurrent hemoptysis and pneumonia. Presentation in adulthood
      without additional congenital heart disease is rare but does occur. Anatomic
      variations in the pulmonary vessels that supply and drain the affected lung can
      explain the mildly symptomatic process. The diagnosis of isolated unilateral
      pulmonary vein atresia is usually made angiographically. Pneumonectomy is
      indicated once symptoms or complications are present so that irreversible
      pulmonary hypertension can be avoided.

PMID- 21169145
TI  - Rare variation in partial anomalous venous drainage in 2 cases: diagnosis,
      assessment methods, and surgical approach.
AB  - Where pulmonary veins drain and their relationship with an atrial septal defect
      (ASD) are important. A sinus venosus (high venosum) type of defect is the most
      common pathology accompanying partial anomalous pulmonary venous connection.
      Typically, the right superior pulmonary vein and occasionally the middle
      pulmonary vein drain into the junction of the superior vena cava (SVC) and the
      right atrium (RA), and a sinus venosus type of ASD usually accompanies these
      anomalies. In this report, we assess a very rare pathology in which 3 right
      pulmonary veins (superior, middle, and inferior) drain into the SVC-RA junction
      with respect to diagnostic methods and in the light of 2 cases involving patients
      in 2 different age groups.

PMID- 21169146
TI  - Fulminant Neisseria meningitidis: role for extracorporeal membrane oxygenation.
AB  - Invasive meningococcal disease is often associated with complications of septic
      shock and central nervous system dysfunction. Extracorporeal membrane oxygenation
      is more commonly being used for respiratory failure and sepsis, but neurologic
      injury and potential coagulopathy are often considered relative
      contraindications. We report a successful case of complicated Neisseria
      meningitidis septic shock with disseminated intravascular coagulopathy requiring
      extracorporeal support.

PMID- 21169147
TI  - A new practical alternative for the control of sternal bleeding during cardiac
      surgery: Ankaferd Blood Stopper.
AB  - The control of sternal bleeding during cardiac surgery can sometimes be a
      challenging and time-consuming problem for surgeons. Several alternatives for the
      control of sternal bleeding are on the market. Bone wax is a well-known
      alternative used by many cardiac surgeons for the control of bleeding. It is
      effective and cheap; however, it inhibits ossification of the sternum and can
      cause infections and sternal wound healing problems after cardiac surgery.
      Consequently, control of sternal bleeding without the use of bone wax requires
      meticulous preparation. Ankaferd Blood Stopper (ABS) (Ankaferd Saglik Urunleri,
      Istanbul, Turkey) is a unique folkloric medicinal plant extract that has been
      used in Turkish traditional medicine as a hemostatic agent. We present a
      practical alternative technique for the control of sternal bleeding during
      cardiac surgery with the use of ABS.

PMID- 21169149
TI  - Single-lung ventilation time does not increase lung injury after totally
      endoscopic coronary artery bypass surgery.
AB  - INTRODUCTION: Over the last decade, totally endoscopic procedures on the beating
      heart and on the arrested heart have made their way into cardiac surgery. Single
      lung ventilation (SLV) is a prerequisite for performing totally endoscopic
      coronary artery bypass surgery (TECAB). The aim of the present study was to
      evaluate the influence of SLV on perioperative respiratory parameters and to
      determine additional predictors of respiratory problems in these patients.
      PATIENTS AND METHODS: We investigated 16 female and 69 male patients (median age,
      59 years; range, 38-90 years) who underwent either arrested heart TECAB (n = 76)
      or beating heart TECAB (n = 9). We analyzed the correlations of the SLV,
      cardiopulmonary bypass (CPB), aortic cross-clamping, and overall procedure times
      with perioperative respiratory parameters and length of intensive care unit (ICU)
      stay. RESULTS: Preoperative values for forced vital capacity and the forced
      expiratory volume in 1 second were negatively correlated with postoperative
      pulmonary dysfunction. Longer total operative times were correlated with
      prolonged mechanical ventilation, tube continuous positive airway pressure
      ventilation (tube CPAP) time, and ICU and hospital stays. Increased CPB times
      were associated with longer tube CPAP times, higher grades of pulmonary
      dysfunction, and a prolonged hospital stay. A prolonged aortic-occlusion time
      increased the postoperative time to extubation and the hospital stay.
      Postoperative pulmonary dysfunction was associated with a history of smoking, a
      poor preoperative respiratory status, and a prolonged CPB time. SLV, however, did
      not correlate with postoperative time to extubation or with length of ICU stay.
      Only in patients who underwent conversion to sternotomy (n = 13) was SLV
      associated with prolonged mechanical ventilation. CONCLUSIONS: Preoperative
      respiratory status showed no major influence on postoperative respiratory outcome
      in selected patients. Longer operative, CPB, and aortic crossclamping times led
      to reversible lung injury after TECAB. Prolonged SLV times, however, did not
      increase the postoperative time to extubation or the length of ICU stay in TECAB
      patients.

PMID- 21169150
TI  - The Thoratec system implanted as a modified total artificial heart: the Bad
      Oeynhausen technique.
AB  - The CardioWestTM total artificial heart (SynCardia Systems, Tuscon, AZ, USA) is
      the only FDA-approved total artificial heart determined as a bridge to human
      heart transplantation for patients dying of biventricular heart failure.
      Implantation provides immediate hemodynamic restoration and clinical
      stabilization, leading to end-organ recovery and thus eventually allowing cardiac
      transplantation. Occasionally, implantation of a total artificial heart is not
      feasible for anatomical reasons. For this patient group, we have developed an
      alternative technique using the paracorporeal Thoratec biventricular support
      system (Thoratec, Pleasanton, CA, USA) as a modified total artificial heart. A
      detailed description of the implantation technique is presented.

PMID- 21169151
TI  - Robotic totally endoscopic triple coronary artery bypass grafting on the arrested
      heart: report of the first successful clinical case.
AB  - Robotic technology enables "port only" totally endoscopic coronary artery bypass
      grafting (TECAB). During early procedure development only single bypass grafts
      were feasible. Because current referral practice for coronary bypass surgery
      mostly includes multivessel disease, performance of multiple endoscopic bypass
      grafts is desirable. We report a case in which a patient received a right
      internal mammary artery bypass graft to the left anterior descending artery and a
      left internal mammary artery jump graft to 2 obtuse marginal branches. The
      procedure was performed through 5 ports on the arrested heart using the daVinci S
      robotic surgical system. This is the first reported triple bypass grafting
      procedure using an arrested heart approach.

PMID- 21169152
TI  - Cardiac angiosarcoma with reconstruction of the right atrium.
AB  - We describe a case of a 65-year-old female patient who presented with shortness
      of breath when bending forward. A tumor highly suspicious for an angiosarcoma was
      identified by computed tomography and was suggestive of infiltration into the
      superior vena cava (SVC) and the majority of the right atrium. Surgical
      intervention on such an infiltrative tumor would not have been indicated.
      Magnetic resonance imaging, however, demonstrated that the tumor was not
      infiltrating the SVC and that its extension into the right atrium caused a low
      flow phenomenon. Surgical removal of the tumor and reconstruction of the right
      atrium with bovine pericardium was performed successfully. Adjuvant treatment
      with chemotherapy and radiation was performed afterward. The patient is free from
      tumor recurrence 3 months postoperatively.

PMID- 21169153
TI  - Is an intraaortic balloon pump a contraindication to robotic totally endoscopic
      coronary artery bypass?
AB  - BACKGROUND: The success of robotic totally endoscopic coronary artery bypass
      (TECAB) in recent years has led to the expansion of the procedure to patients
      with more severe disease. Outcomes with these patients have not yet been well
      characterized, and no reports on TECAB performed in patients with a
      preoperatively placed intraaortic balloon pump (IABP) are available. We present
      our initial experience with this patient population. PATIENTS AND METHODS: We
      evaluated 5 patients with unstable angina or impaired left ventricular function
      requiring a preoperatively placed IABP who underwent TECAB using the daVinci
      telemanipulation system. Procedures were performed either on the beating heart
      using an endostabilizer (n = 2) or on the arrested heart using remote access
      perfusion and aortic balloon endoocclusion (n = 3). The median patient age was 67
      years (range, 41-73 years), with a median preoperative ejection fraction of 43%
      (range, 26%-58%) and median EuroSCORE of 5 (range, 3-8). RESULTS: There were no
      major intraoperative technical issues. The median length of stay in the hospital
      and intensive care unit was 8 days (range, 5-13 days) and 66 hours (range, 41-142
      hours), respectively. There were no intraoperative or 30-day mortalities.
      CONCLUSIONS: This early experience suggests that TECAB is feasible in patients
      with a preoperatively placed IABP. Both the beating heart and arrested heart
      versions can be used in this patient population, further broadening the spectrum
      of applicability of this procedure.

PMID- 21169154
TI  - Dissection of the left main coronary artery during percutaneous intervention:
      successful surgical management.
AB  - Coronary dissection during diagnostic catheterization presents a therapeutic
      challenge. Medical management or percutaneous intervention may be an option in a
      stable patient. Unstable patients should promptly undergo surgical
      revascularization. We report on a patient in whom dissection of the left main
      coronary artery, the left anterior descending artery, and a diagonal branch
      occurred during catheterization. Clear signs of myocardial ischemia indicated
      immediate surgery. Coronary artery bypass grafting was carried out within a very
      short time frame and the patient survived. This case demonstrates the value of an
      expeditious surgical treatment strategy.

PMID- 21169155
TI  - Hybrid coronary revascularization: an overview of options for anticoagulation and
      platelet inhibition.
AB  - BACKGROUND: Hybrid coronary revascularization, in which coronary bypass grafting
      is combined with percutaneous coronary intervention, is a promising strategy for
      optimizing outcomes in the treatment of coronary artery disease. Balancing the
      risk of surgical bleeding with the risk of percutaneous coronary intervention
      related thrombosis is a major challenge inherent in carrying out a successful
      procedure and requires careful selection of antiplatelet and anticoagulant
      agents. METHODS: Advantages and disadvantages of antiplatelet and anticoagulant
      agents in use today for hybrid coronary revascularization are reviewed. RESULTS:
      Currently available anticoagulants and platelet inhibitors have been used to
      provide safe and effective protection from thrombosis while limiting surgical
      bleeding in hybrid coronary revascularization, but there is no agreement on an
      optimal strategy, and each patient presents a unique pharmacologic and logistic
      puzzle. CONCLUSION: Knowledge of the salient features of the available
      medications will allow the cardiologist and surgeon to design the optimal
      strategy for each patient.

PMID- 21169156
TI  - Comprehensive management of severe intestinal bleeding in a patient supported for
      94 days by the biventricular Levitronix CentriMag system.
AB  - The use of short-term mechanical circulatory support during postcardiotomy acute
      heart failure provides an opportunity to stabilize the patient's hemodynamic
      state while determining the best long-term strategy. Because all of these devices
      require anticoagulation treatment of various intensities, management of major
      bleeding can be critical for the overall outcome of the therapy. In this regard,
      the newest generation of magnetically levitated centrifugal-flow pumps affords
      several potential advantages in terms of thrombogenicity and eventual
      discontinuation of anticoagulation treatment. We report the use of a short-term
      biventricular assist device (Levitronix CentriMag) for 94 days in a 55-year-old
      man with refractory ventricular arrhythmias after combined heart surgery. Despite
      serious complications while the patient was on the assist device, including
      severe intestinal bleeding with the necessity of discontinuing anticoagulation
      for 10 days and, ultimately, hemicolectomy, the circulatory support was completed
      with successful heart transplantation.

PMID- 21169157
TI  - Concomitant aortic valve replacement and gastrectomy for gastric cancer.
AB  - A 75-year-old male patient developed hematemesis due to gastric cancer 1 week
      before scheduled aortic valve replacement for severe aortic stenosis. A
      gastrectomy was urgently required, but the risk of intraoperative cardiac
      decompensation was judged as too high because of the severity of his cardiac
      disease. On the other hand, cardiopulmonary bypass posed an exceedingly high risk
      of bleeding from the stomach cancer. Concomitant aortic valve replacement and
      gastrectomy were performed successfully.

PMID- 21169158
TI  - Management of biventricular assist device implantation in patients with necrotic
      pancreatitis.
AB  - This report describes the management of biventricular assist device (BIVAD)
      implantation in a patient with necrotic pancreatitis. BIVADs provide mechanical
      support for ventricular ejection in the failing heart and have become an accepted
      treatment for end-stage heart failure. They also have proved to be a successful
      bridge to heart transplantation. As their popularity has grown, the number of
      patients with BIVADs presenting for noncardiac surgery is increasing. We report
      the successful management of an implanted extracorporeal BIVAD in a patient with
      end-stage heart failure and with pancreatic stents in a case of necrotic
      pancreatitis. Historical, physical, laboratory, and imaging data allowed
      conservative management leading to a favorable outcome.

PMID- 21169159
TI  - Development and evaluation of the personal patient profile-prostate (P3P), a Web
      based decision support system for men newly diagnosed with localized prostate
      cancer.
AB  - BACKGROUND: Given that no other disease with the high incidence of localized
      prostate cancer (LPC) has so many treatments with so few certainties related to
      outcomes, many men are faced with assuming some responsibility for the treatment
      decision along with guidance from clinicians. Men strongly consider their own
      personal characteristics and other personal factors as important and influential
      to the decision. Clinical researchers have not developed or comprehensively
      investigated interventions to facilitate the insight and prioritizing of personal
      factors along with medical factors that are required of a man in preparation for
      the treatment decision. OBJECTIVES: The purpose of this pilot study was to
      develop and evaluate the feasibility and usability of a Web-based decision
      support technology, the Personal Patient Profile-Prostate (P3P), in men newly
      diagnosed with LPC. METHODS: Use cases were developed followed by infrastructure
      and content application. The program was provided on a personal desktop computer
      with a touch screen monitor. Participant responses to the query component of P3P
      determined the content of the multimedia educational and coaching intervention.
      The intervention was tailored to race, age, and personal factors reported as
      influencing the decision. Prepilot usability testing was conducted using a "think
      aloud" interview to identify navigation and content challenges. These issues were
      addressed prior to deployment in the clinic. A clinical pilot was conducted in an
      academic medical center where men sought consultation and treatment for LPC.
      Completion time, missing data, and acceptability were measured. RESULTS: Prepilot
      testing included 4 men with a past diagnosis of LPC who had completed therapy.
      Technical navigation issues were documented along with confusing content
      language. A total of 30 additional men with a recent diagnosis of LPC completed
      the P3P program in clinic prior to consulting with a urologist regarding
      treatment options. In a mean time of 46 minutes (SD 13 minutes), participants
      completed the P3P query and intervention components. Of a possible 4560 items for
      30 participants, 22 (0.5%) were missing. Acceptability was reported as high
      overall. The sections of the intervention reported as most useful were the
      statistics graphs, priority information topics, and annotated external website
      links. CONCLUSIONS: The P3P intervention is a feasible and usable program to
      facilitate treatment decision making by men with newly diagnosed LPC. Testing in
      a multisite randomized trial with a diverse sample is warranted.

PMID- 21169160
TI  - An online community improves adherence in an internet-mediated walking program.
      Part 1: results of a randomized controlled trial.
AB  - BACKGROUND: Approximately half of American adults do not meet recommended
      physical activity guidelines. Face-to-face lifestyle interventions improve health
      outcomes but are unlikely to yield population-level improvements because they can
      be difficult to disseminate, expensive to maintain, and inconvenient for the
      recipient. In contrast, Internet-based behavior change interventions can be
      disseminated widely at a lower cost. However, the impact of some Internet
      mediated programs is limited by high attrition rates. Online communities that
      allow participants to communicate with each other by posting and reading messages
      may decrease participant attrition. OBJECTIVE: Our objective was to measure the
      impact of adding online community features to an Internet-mediated walking
      program on participant attrition and average daily step counts. METHODS: This
      randomized controlled trial included sedentary, ambulatory adults who used email
      regularly and had at least 1 of the following: overweight (body mass index [BMI]
      >= 25), type 2 diabetes, or coronary artery disease. All participants (n = 324)
      wore enhanced pedometers throughout the 16-week intervention and uploaded step
      count data to the study server. Participants could log in to the study website to
      view graphs of their walking progress, individually-tailored motivational
      messages, and weekly calculated goals. Participants were randomized to 1 of 2
      versions of a Web-based walking program. Those randomized to the "online
      community" arm could post and read messages with other participants while those
      randomized to the "no online community" arm could not read or post messages. The
      main outcome measures were participant attrition and average daily step counts
      over 16 weeks. Multiple regression analyses assessed the effect of the online
      community access controlling for age, sex, disease status, BMI, and baseline step
      counts. RESULTS: Both arms significantly increased their average daily steps
      between baseline and the end of the intervention period, but there were no
      significant differences in increase in step counts between arms using either
      intention-to-treat or completers analysis. In the intention-to-treat analysis,
      the average step count increase across both arms was 1888 +/- 2400 steps. The
      percentage of completers was 13% higher in the online community arm than the no
      online community arm (online community arm, 79%, no online community arm, 66%, P
      = .02). In addition, online community arm participants remained engaged in the
      program longer than no online community arm participants (hazard ratio = 0.47,
      95% CI = 0.25 - 0.90, P = .02). Participants with lower baseline social support
      posted more messages to the online community (P < .001) and viewed more posts (P
      < .001) than participants with higher baseline social support. CONCLUSION: Adding
      online community features to an Internet-mediated walking program did not
      increase average daily step counts but did reduce participant attrition.
      Participants with low baseline social support used the online community features
      more than those with high baseline social support. Thus, online communities may
      be a promising approach to reducing attrition from online health behavior change
      interventions, particularly in populations with low social support. TRIAL
      REGISTRATION: NCT00729040; http://clinicaltrials.gov/ct2/show/NCT00729040
      (Archived by WebCite at http://www.webcitation.org/5v1VH3n0A).

PMID- 21169161
TI  - Adding an online community to an internet-mediated walking program. Part 2:
      strategies for encouraging community participation.
AB  - Starting a new online community with a limited number of members who have not
      self-selected for participation in the community is challenging. The space must
      appear active to lure visitors to return; when the pool of participants is small,
      a large fraction must be converted from lurkers to contributors, and contributors
      must receive responses quickly to encourage continued participation. We report on
      strategies for overcoming these challenges and our experience implementing them
      within an online community add-on to an existing Internet-mediated walking
      program. Concentrated study recruitment increased the effective membership size.
      Having few conversation spaces rather than many specialized ones, staff seeding
      of the forums before members were invited to visit, and staff posting of new
      topics when there were conversation lulls, all helped to make the forums appear
      active. In retrospect, using even fewer separate spaces and displaying a flat
      rather than nested reply structure would have made the forums appear even more
      active. Contests with small prizes around participation in the forums and around
      meeting walking goals generated a lot of discussion; a contest for first-time
      posters was especially effective at moving lurkers to post. Staff efforts to
      elicit participation by asking questions had mixed success. Staff replies to
      posts that had not received member replies created a feeling of responsiveness
      despite limited membership.

PMID- 21169162
TI  - Using evidence-based internet interventions to reduce health disparities
      worldwide.
AB  - Health disparities are a persistent problem worldwide. A major obstacle to
      reducing health disparities is reliance on "consumable interventions," that is,
      interventions that, once used, cannot be used again. To reduce health
      disparities, interventions are required that can be used again and again without
      losing their therapeutic power, that can reach people even if local health care
      systems do not provide them with needed health care, and that can be shared
      globally without taking resources away from the populations where the
      interventions were developed. This paper presents the argument that automated
      self-help evidence-based Internet interventions meet the above criteria and can
      contribute to the reduction of health disparities worldwide. Proof-of-concept
      studies show that evidence-based Internet interventions can reach hundreds of
      thousands of people worldwide and could be used in public sector settings to
      augment existing offerings and provide services not currently available (such as
      prevention interventions). This paper presents a framework for systematically
      filling in a matrix composed of columns representing common health problems and
      rows representing languages. To bring the benefits of evidence-based Internet
      interventions to the underserved, public sector clinics should establish eHealth
      resource centers, through which patients could be screened online for common
      disorders and provided with evidence-based Internet intervention services not
      currently available at the clinics. These resources should be available in the
      patients' languages, in formats that do not require literacy, and that can be
      accessed with mobile devices. Such evidence-based Internet interventions should
      then be shared with public sector clinics as well as individuals anywhere in the
      world. Finally, this paper addresses sustainability and describes a continuum of
      evidence-based Internet interventions to share nationally and across the world.
      This approach to expanding health service delivery will significantly contribute
      to a reduction of health disparities worldwide, adding to the often-quoted
      slogan, "Think globally, act locally," a third line: "Share globally."

PMID- 21169164
TI  - Multimodal e-mental health treatment for depression: a feasibility trial.
AB  - BACKGROUND: Internet interventions for depression have shown less than optimal
      adherence. This study describes the feasibility trial of a multimodal e-mental
      health intervention designed to enhance adherence and outcomes for depression.
      The intervention required frequent brief log-ins for self-monitoring and feedback
      as well as email and brief telephone support guided by a theory-driven manualized
      protocol. OBJECTIVE: The objective of this feasibility trial was to examine if
      our Internet intervention plus manualized telephone support program would result
      in increased adherence rates and improvement in depression outcomes. METHODS:
      This was a single arm feasibility trial of a 7-week intervention. RESULTS: Of the
      21 patients enrolled, 2 (9.5%) dropped out of treatment. Patients logged in 23.2
      +/- 12.2 times over the 7 weeks. Significant reductions in depression were found
      on all measures, including the Patient Health Questionnaire depression scale (PHQ
      8) (Cohen's d = 1.96, P < .001), the Hamilton Rating Scale for Depression (d =
      1.34, P < .001), and diagnosis of major depressive episode (P < .001).
      CONCLUSIONS: The attrition rate was far lower than seen either in Internet
      studies or trials of face-to-face interventions, and depression outcomes were
      substantial. These findings support the feasibility of providing a multimodal e
      mental health treatment to patients with depression. Although it is premature to
      make any firm conclusions based on these data, they do support the initiation of
      a randomized controlled trial examining the independent and joint effects of
      Internet and telephone administered treatments for depression.

PMID- 21169163
TI  - Consumers' perceptions about and use of the internet for personal health records
      and health information exchange: analysis of the 2007 Health Information National
      Trends Survey.
AB  - BACKGROUND: Personal health records (PHRs) and the sharing of health information
      through health information exchange (HIE) have been advocated as key new
      components in the effective delivery of modern health care. It is important to
      understand consumer attitudes toward utilization of PHRs and HIE to evaluate the
      public's willingness to adopt these new health care tools. OBJECTIVE: The purpose
      of this study was to examine consumer attitudes toward PHRs and their health care
      providers' use of HIE, as well as to evaluate consumer use of the Internet for
      tracking PHRs. METHODS: Analysis of data from the 2007 iteration of the Health
      Information National Trends Study (HINTS, N=7674) was conducted using
      multivariate logistic regression to identify predictors of consumer (1) appraisal
      of PHRs, (2) appraisal of health care provider use of HIE, and (3) use of the
      Internet for tracking PHRs. RESULTS: Approximately 86% of US adults rated
      electronic access to their PHRs as important. However, only 9% of them used the
      Internet for tracking PHRs. Those who rated electronic access to their PHRs as
      important were more likely to be Hispanic (odds ratio [OR] = 1.34, 95% confidence
      interval [CI] 1.04 - 1.72) and Internet users (OR = 1.27, 95% CI = 1.02 - 1.57)
      and less likely to be age 65 and above (OR = 0.50, 95% CI = 0.38 - 0.67) or
      individuals whose doctors always ensured their understanding of their health (OR
      = 0.62, 95% CI = 0.49 - 0.78). Those who rated HIE as important were more likely
      to be 45 to 54 years of age (OR = 1.46, 95% CI = 1.03 - 2.08), 55 to 64 years of
      age (OR = 1.83, 95% CI = 1.32 - 2.53), or 65 and above (OR = 1.76, 95% CI = 1.27 
      2.43) and less likely to be women (OR = 0.80, 95% CI = 0.68 - 0.95) or
      individuals who perceive their health information as not safely guarded by their
      doctors (OR = 0.53, 95% CI = 0.40 - 0.69). Among Internet users, those who used
      the Internet to track their PHRs were more likely to be college graduates (OR =
      1.84, 95% = 1.32 - 2.59) or to have completed some college courses (OR = 1.46,
      95% CI = 1.02 - 2.11), to be Hispanic (OR = 1.92, 95% CI = 1.23 - 2.98), or to be
      individuals with health care provider access (OR = 1.90, 95% CI = 1.21 - 2.97).
      Women were less likely to use the Internet for tracking PHRs than men (OR = 0.78,
      95% CI = 0.61 - 1.00). CONCLUSIONS: Despite widespread positive appraisal of
      electronic access to PHRs as important, Internet use for tracking PHRs remains
      uncommon. To promote PHR adoption, the digital divide associated with the gap in
      health literacy must be improved, and cultural issues and the doctor-patient
      relationship need to be studied. Further work also needs to address consumer
      concerns regarding the security of HIE.

PMID- 21169165
TI  - A comparison of psychometric properties between internet and paper versions of
      two depression instruments (BDI-II and MADRS-S) administered to clinic patients.
AB  - BACKGROUND: Self-report measures can guide clinical decisions and are useful when
      evaluating treatment outcomes. However, many clinicians do not use self-report
      measures systematically in their clinical practice. Internet-based questionnaires
      could facilitate administration, but the psychometric properties of the online
      version of an instrument should be explored before implementation. The
      recommendation from the International Test Commission is to test the psychometric
      properties of each questionnaire separately. OBJECTIVE: Our objective was to
      compare the psychometric properties of paper-and-pencil versions and Internet
      versions of two questionnaires measuring depressive symptoms. METHODS: The 87
      participating patients were recruited from primary care and psychiatric care
      within the public health care system in Sweden. Participants completed the Beck
      Depression Inventory (BDI-II) and the Montgomery-Asberg Depression Rating Scale
      Self-rated (MADRS-S), both on paper and on the Internet. The order was randomized
      to control for order effects. Symptom severity in the sample ranged from mild to
      severe depressive symptoms. RESULTS: Psychometric properties of the two
      administration formats were mostly equivalent. The internal consistency was
      similar for the Internet and paper versions, and significant correlations were
      found between the formats for both MADRS-S (r = .84) and the BDI-II (r = .89).
      Differences between paper and Internet total scores were not statistically
      significant for either questionnaire nor for the MADRS-S question dealing with
      suicidality (item 9) when analyzed separately. The score on the BDI-II question
      about suicidality (item 9) was significantly lower when administered via the
      Internet compared with the paper score, but the difference was small (effect
      size, Cohen's [d] = 0.14). There were significant main effects for order of
      administration on both questionnaires and significant interaction effects between
      format and order. This should not, however, pose a problem in clinical use as
      long as the administration format is not changed when repeated measurements are
      made. CONCLUSIONS: The MADRS-S can be transferred to online use without affecting
      the psychometric properties in a clinically meaningful way. The full BDI-II also
      seems to retain its properties when transferred; however, the item measuring
      suicidality in the Internet version needs further investigation since it was
      associated with a lower score in this study. The use of online questionnaires
      offers clinicians a more practical way of measuring depressive symptoms and has
      the potential to save resources.

PMID- 21169166
TI  - Cost-utility and cost-effectiveness of internet-based treatment for adults with
      depressive symptoms: randomized trial.
AB  - BACKGROUND: The effectiveness of Internet-based treatments for depression has
      been demonstrated; their cost-effectiveness, however, has been less well
      researched. OBJECTIVE: Evaluating the relative cost-utility and cost
      effectiveness of (1) Internet-based cognitive behavioral therapy, (2) Internet
      based problem-solving therapy, and (3) a waiting list for adults with depressive
      symptoms. METHODS: A total of 263 participants with clinically significant
      depressive symptoms were randomized to Internet-based cognitive behavioral
      therapy (n = 88), Internet-based problem-solving therapy (n = 88), and a waiting
      list (n = 87). End points were evaluated at the 12-week follow-up. RESULTS: Cost
      utility analysis showed that cognitive behavioral therapy and problem-solving
      therapy had a 52% and 61% probability respectively of being more acceptable than
      waiting when the willingness to pay is ? 30,000 for one quality-adjusted life
      year. When society is prepared to pay ? 10,000 for a clinically significant
      change from depression, the probabilities of cognitive behavioral therapy and
      problem-solving therapy being more acceptable than waiting are 91% and 89%,
      respectively. Comparing both Internet-based treatments showed no clear preference
      for one or the other of the treatments. CONCLUSIONS: Both Internet-based
      treatments have a high probability of being cost-effective with a modest value
      placed on clinically significant change in depressive symptoms. TRIAL
      REGISTRATION: ISRCTN16823487; http://www.controlled-trials.com/ISRCTN16823487
      (Archived by WebCite at http://www.webcitation.org/5u8slzhDE).

PMID- 21169167
TI  - Missing data approaches in eHealth research: simulation study and a tutorial for
      nonmathematically inclined researchers.
AB  - BACKGROUND: Missing data is a common nuisance in eHealth research: it is hard to
      prevent and may invalidate research findings. OBJECTIVE: In this paper several
      statistical approaches to data "missingness" are discussed and tested in a
      simulation study. Basic approaches (complete case analysis, mean imputation, and
      last observation carried forward) and advanced methods (expectation maximization,
      regression imputation, and multiple imputation) are included in this analysis,
      and strengths and weaknesses are discussed. METHODS: The dataset used for the
      simulation was obtained from a prospective cohort study following participants in
      an online self-help program for problem drinkers. It contained 124 nonnormally
      distributed endpoints, that is, daily alcohol consumption counts of the study
      respondents. Missingness at random (MAR) was induced in a selected variable for
      50% of the cases. Validity, reliability, and coverage of the estimates obtained
      using the different imputation methods were calculated by performing a
      bootstrapping simulation study. RESULTS: In the performed simulation study, the
      use of multiple imputation techniques led to accurate results. Differences were
      found between the 4 tested multiple imputation programs: NORM, MICE, Amelia II,
      and SPSS MI. Among the tested approaches, Amelia II outperformed the others, led
      to the smallest deviation from the reference value (Cohen's d = 0.06), and had
      the largest coverage percentage of the reference confidence interval (96%).
      CONCLUSIONS: The use of multiple imputation improves the validity of the results
      when analyzing datasets with missing observations. Some of the often-used
      approaches (LOCF, complete cases analysis) did not perform well, and, hence, we
      recommend not using these. Accumulating support for the analysis of multiple
      imputed datasets is seen in more recent versions of some of the widely used
      statistical software programs making the use of multiple imputation more readily
      available to less mathematically inclined researchers.

PMID- 21169168
TI  - Content and functionality of alcohol and other drug websites: results of an
      online survey.
AB  - BACKGROUND: There is a growing trend for individuals to seek health information
      from online sources. Alcohol and other drug (AOD) use is a significant health
      problem worldwide, but access and use of AOD websites is poorly understood.
      OBJECTIVE: To investigate content and functionality preferences for AOD and other
      health websites. METHODS: An anonymous online survey examined general Internet
      and AOD-specific usage and search behaviors, valued features of AOD and health
      related websites (general and interactive website features), indicators of
      website trustworthiness, valued AOD website tools or functions, and treatment
      modality preferences. RESULTS: Surveys were obtained from 1214 drug (n = 766) and
      alcohol website users (n = 448) (mean age 26.2 years, range 16-70). There were no
      significant differences between alcohol and drug groups on demographic variables,
      Internet usage, indicators of website trustworthiness, or on preferences for AOD
      website functionality. A robust website design/navigation, open access, and
      validated content provision were highly valued by both groups. While
      attractiveness and pictures or graphics were also valued, high-cost features
      (videos, animations, games) were minority preferences. Almost half of respondents
      in both groups were unable to readily access the information they sought. Alcohol
      website users placed greater importance on several AOD website tools and
      functions than did those accessing other drug websites: online screening tools
      (chi2(2) = 15.8, P < .001, n = 985); prevention programs (chi2(2) = 27.5, P <
      .001, n = 981); tracking functions (chi2(2) = 11.5, P = .003, n = 983); self help
      treatment programs (chi2(2) = 8.3, P = .02, n = 984); downloadable fact sheets
      for friends (chi2(2) = 11.6, P = .003, n = 981); or family (chi2(2) = 12.7, P =
      .002, n = 983). The most preferred online treatment option for both the user
      groups was an Internet site with email therapist support. Explorations of
      demographic differences were also performed. While gender did not affect survey
      responses, younger respondents were more likely to value interactive and social
      networking features, whereas downloading of credible information was most highly
      valued by older respondents. CONCLUSIONS: Significant deficiencies in the
      provision of accessible information on AOD websites were identified, an important
      problem since information seeking was the most common reason for accessing these
      websites, and, therefore, may be a key avenue for engaging website users in
      behaviour change. The few differences between AOD website users suggested that
      both types of websites may have similar features, although alcohol website users
      may more readily be engaged in screening, prevention and self-help programs,
      tracking change, and may value fact sheets more highly. While the
      sociodemographic differences require replication and clarification, these
      differences support the notion that the design and features of AOD websites
      should target specific audiences to have maximal impact.

PMID- 21169169
TI  - The ins and outs of an online bipolar education program: a study of program
      attrition.
AB  - BACKGROUND: The science of eHealth interventions is rapidly evolving. However,
      despite positive outcomes, evaluations of eHealth applications have thus far
      failed to explain the high attrition rates that are associated with some eHealth
      programs. Patient adherence remains an issue, and the science of attrition is
      still in its infancy. To our knowledge, there has been no in-depth qualitative
      study aimed at identifying the reasons for nonadherence to-and attrition from-
      online interventions. OBJECTIVE: This paper explores the predictors of attrition
      and participant-reported reasons for nonadherence to an online psycho-education
      program for people newly diagnosed with a bipolar disorder. METHODS: As part of
      an ongoing randomized controlled trial (RCT) evaluating an online psycho
      education program for people newly diagnosed with a bipolar disorder, we
      undertook an in-depth qualitative study to identify participants' reasons for
      nonadherence to, and attrition from, the online intervention as well as a
      quantitative study investigating predictors of attrition. Within the RCT, 370
      participants were randomly allocated to 1 of 2 active interventions or an
      attention control condition. Descriptive analyses and chi-square tests were used
      to explore the completion rates of 358 participants, and standard regression
      analysis was used to identify predictors of attrition. The data from interviews
      with a subsample of 39 participants who did not complete the online program were
      analyzed using "thematic analysis" to identify patterns in reported reasons for
      attrition. RESULTS: Overall, 26.5% of the sample did not complete their assigned
      intervention. Standard multiple regression analysis revealed that young age (P=
      .004), male gender (P= .001), and clinical recruitment setting (P= .001) were
      significant predictors of attrition (F(7,330)= 8.08, P< .001). Thematic analysis
      of interview data from the noncompleter subsample revealed that difficulties
      associated with the acute phases of bipolar disorder, not wanting to think about
      one's illness, and program factors such as the information being too general and
      not personally tailored were the major reasons for nonadherence. CONCLUSIONS: The
      dropout rate was equivalent to other Internet interventions and to face-to-face
      therapy. Findings from our qualitative study provide participant-reported reasons
      for discontinuing the online intervention, which, in conjunction with the
      quantitative investigations about predictors, add to understanding about Internet
      interventions. However, further research is needed to determine whether there are
      systematic differences between those who complete and those who do not complete
      eHealth interventions. Ultimately, this may lead to the identification of
      population subgroups that most benefit from eHealth interventions and to
      informing the development of strategies to improve adherence. TRIAL REGISTRATION:
      ACTRN12608000411347; http://www.anzctr.org.au/ACTRN12608000411347.aspx (Archived
      by WebCite at http://www.webcitation.org/5uX4uYwVN).

PMID- 21169170
TI  - Ethical dilemmas in online research and treatment of sexually abused adolescents.
AB  - BACKGROUND: In a recent uncontrolled trial of a new therapist-assisted Web-based
      treatment of adolescent victims of sexual abuse, the treatment effects were found
      to be promising. However, the study suffered a large pretreatment withdrawal rate
      that appeared to emanate from reluctance among the participants to disclose their
      identity and obtain their parents' consent. OBJECTIVE: Our objectives were to
      confirm the effects of the online treatment in a controlled trial and to evaluate
      measures to reduce pretreatment withdrawal in vulnerable populations including
      young victims of sexual abuse. METHODS: The study was designed as a within
      subject baseline-controlled trial. Effects of an 8-week attention-placebo
      intervention were contrasted with the effects of an 8-week treatment episode.
      Several measures were taken to reduce pretreatment dropout. RESULTS: Pretreatment
      withdrawal was reduced but remained high (82/106, 77%). On the other hand,
      treatment dropout was low (4 out of 24 participants), and improvement during
      treatment showed significantly higher effects than during the attention placebo
      control period (net effect sizes between 0.5 and 1.6). CONCLUSIONS: In treatment
      of vulnerable young populations, caregivers and researchers will have to come to
      terms with high pretreatment withdrawal rates. Possible measures may reduce
      pretreatment withdrawal to some degree. Providing full anonymity is not a viable
      option since it is incompatible with the professional responsibility of the
      caregiver and restricts research possibilities.

PMID- 21169171
TI  - Providing web-based feedback and social norms information to reduce student
      alcohol intake: a multisite investigation.
AB  - BACKGROUND: Unhealthy alcohol use among university students is cause for concern,
      yet the level of help seeking behavior for alcohol use is low within the student
      population. Electronic brief interventions delivered via the Internet present an
      alternative to traditional treatments and could enable the delivery of
      interventions on a population basis. Further evidence is needed of the
      effectiveness of Internet-delivered interventions and of their generalizability
      across educational institutions. OBJECTIVE: Our objective was to evaluate the
      effectiveness across 4 UK universities of a Web-based intervention for student
      alcohol use. METHODS: In total, 1112 participants took part. Participants were
      stratified by educational institution, gender, age group, year of study, and self
      reported weekly consumption of alcohol and randomly assigned to either the
      control arm or to the immediate or delayed intervention arms. Intervention
      participants gained access to the intervention between weeks 1 to 7 or weeks 8 to
      15, respectively. The intervention provided electronic personalized feedback and
      social norms information on drinking behavior accessed by logging on to a
      website. Participants registered interest by completing a brief screening
      questionnaire and were then asked to complete 4 further assessments across the 24
      weeks of the study. Assessments included a retrospective weekly drinking diary,
      the Alcohol Use Disorders Identification Test (AUDIT), and a readiness-to-change
      algorithm. The outcome variable was the number of units of alcohol consumed in
      the last week. The effect of treatment arm and time on units consumed last week
      and average units consumed per drinking occasion were investigated using repeated
      measures multivariate analysis of covariance (MANCOVA). In addition, the data
      were modeled using a longitudinal regression with time points clustered within
      students. RESULTS: MANCOVA revealed a main effect of time on units of alcohol
      consumed over the last week. A longitudinal regression model showed an effect of
      assessment across time predicting that participants who completed at least 2
      assessments reduced their drinking. The model predicted an additional effect of
      being assigned to an intervention arm, an effect that increased across time.
      Regression analysis predicted that being male or being assigned to an
      intervention arm increased the odds of not completing all assessments. The number
      of units of alcohol consumed over the last week at registration, age, university
      educational institution, and readiness to change were not predictive of
      completion. CONCLUSIONS: Delivering an electronic personalized feedback
      intervention to students via the Internet can be effective in reducing weekly
      alcohol consumption. The effect does not appear to differ by educational
      institution. Our model suggested that monitoring alone is likely to reduce weekly
      consumption over 24 weeks but that consumption could be further reduced by
      providing access to a Web-based intervention. Further research is needed to
      understand the apparent therapeutic effect of monitoring and how this can be
      utilized to enhance the effectiveness of brief Web-based interventions.

PMID- 21169172
TI  - Effectiveness of a web-based brief alcohol intervention and added value of
      normative feedback in reducing underage drinking: a randomized controlled trial.
AB  - BACKGROUND: Current insights indicate that Web-based delivery may enhance the
      implementation of brief alcohol interventions. Previous research showed that
      electronically delivered brief alcohol interventions decreased alcohol use in
      college students and adult problem drinkers. To date, no study has investigated
      the effectiveness of Web-based brief alcohol interventions in reducing alcohol
      use in younger populations. OBJECTIVE: The present study tested 2 main
      hypotheses, that is, whether an online multicomponent brief alcohol intervention
      was effective in reducing alcohol use among 15- to 20-year-old binge drinkers and
      whether inclusion of normative feedback would increase the effectiveness of this
      intervention. In additional analyses, we examined possible moderation effects of
      participant's sex, which we had not a priori hypothesized. METHOD: A total of 575
      online panel members (aged 15 to 20 years) who were screened as binge drinkers
      were randomly assigned to (1) a Web-based brief alcohol intervention without
      normative feedback, (2) a Web-based brief alcohol intervention with normative
      feedback, or (3) a control group (no intervention). Alcohol use and moderate
      drinking were assessed at baseline, 1 month, and 3 months after the intervention.
      Separate analyses were conducted for participants in the original sample (n =
      575) and those who completed both posttests (n = 278). Missing values in the
      original sample were imputed by using the multiple imputation procedure of PASW
      Statistics 18. RESULTS: Main effects of the intervention were found only in the
      multiple imputed dataset for the original sample suggesting that the intervention
      without normative feedback reduced weekly drinking in the total group both 1 and
      3 months after the intervention (n =575, at the 1-month follow-up, beta = -.24, P
      = .05; at the 3-month follow-up, beta = -.25, P = .04). Furthermore, the
      intervention with normative feedback reduced weekly drinking only at 1 month
      after the intervention (n=575, beta = -.24, P = .008). There was also a
      marginally significant trend of the intervention without normative feedback on
      responsible drinking at the 3-month follow-up (n =575, beta = .40, P =.07)
      implying a small increase in moderate drinking at the 3-month follow-up.
      Additional analyses on both datasets testing our post hoc hypothesis about a
      possible differential intervention effect for males and females revealed that
      this was the case for the impact of the intervention without normative feedback
      on weekly drinking and moderate drinking at the 1-month follow-up (weekly
      drinking for n = 278, beta = -.80, P = .01, and for n = 575, beta = -.69, P =
      .009; moderate drinking for n = 278, odds ratio [OR] = 3.76, confidence interval
      [CI] 1.05 - 13.49, P = .04, and for n = 575, OR = 3.00, CI = 0.89 - 10.12, P =
      .08) and at the 3-month follow-up (weekly drinking for n = 278, beta = -.58, P =
      .05, and for n = 575, beta = -.75, P = .004; moderate drinking for n = 278, OR =
      4.34, CI = 1.18 - 15.95, P = .04, and for n = 575, OR = 3.65, CI = 1.44 - 9.25, P
      = .006). Furthermore, both datasets showed an interaction effect between the
      intervention with normative feedback and participant's sex on weekly alcohol use
      at the 1-month follow-up (for n = 278, beta = -.74, P =.02, and for n = 575, beta
      = -.64, P =.01) and for moderate drinking at the 3-month follow-up (for n = 278,
      OR = 3.10, CI = 0.81 - 11.85, P = .07, and for n = 575, OR = 3.00, CI = 1.23 -
      7.27, P = .01). Post hoc probing indicated that males who received the
      intervention showed less weekly drinking and were more likely to drink moderately
      at 1 month and at 3 months following the intervention. For females, the
      interventions yielded no effects: the intervention without normative feedback
      even showed a small unfavorable effect at the 1-month follow-up. CONCLUSION: The
      present study demonstrated that exposure to a Web-based brief alcohol
      intervention generated a decrease in weekly drinking among 15- to 20-year-old
      binge drinkers but did not encourage moderate drinking in the total sample.
      Additional analyses revealed that intervention effects were most prominent in
      males resulting in less weekly alcohol use and higher levels of moderate drinking
      among 15- to 20-year-old males over a period of 1 to 3 months. TRIAL
      REGISTRATION: ISRCTN50512934; http://www.controlled-trials.com/ISRCTN50512934/
      (Archived by WebCite at http://www.webcitation.org/5usICa3Tx).

PMID- 21169173
TI  - Security considerations for e-mental health interventions.
AB  - Security considerations are an often overlooked and underfunded aspect of the
      development, delivery, and evaluation of e-mental health interventions although
      they are crucial to the overall success of any eHealth project. The credibility
      and reliability of eHealth scientific research and the service delivery of
      eHealth interventions rely on a high standard of data security. This paper
      describes some of the key methodological, technical, and procedural issues that
      need to be considered to ensure that eHealth research and intervention delivery
      meet adequate security standards. The paper concludes by summarizing broad
      strategies for addressing the major security risks associated with eHealth
      interventions. These include involving information technology (IT) developers in
      all stages of the intervention process including its development, evaluation, and
      ongoing delivery; establishing a wide-ranging discourse about relevant security
      issues; and familiarizing researchers and providers with the security measures
      that must be instituted in order to protect the integrity of eHealth
      interventions.

PMID- 21169174
TI  - Community attitudes to the appropriation of mobile phones for monitoring and
      managing depression, anxiety, and stress.
AB  - BACKGROUND: The benefits of self-monitoring on symptom severity, coping, and
      quality of life have been amply demonstrated. However, paper and pencil self
      monitoring can be cumbersome and subject to biases associated with retrospective
      recall, while computer-based monitoring can be inconvenient in that it relies on
      users being at their computer at scheduled monitoring times. As a result,
      nonadherence in self-monitoring is common. Mobile phones offer an alternative.
      Their take-up has reached saturation point in most developed countries and is
      increasing in developing countries; they are carried on the person, they are
      usually turned on, and functionality is continually improving. Currently,
      however, public conceptions of mobile phones focus on their use as tools for
      communication and social identity. Community attitudes toward using mobile phones
      for mental health monitoring and self-management are not known. OBJECTIVE: The
      objective was to explore community attitudes toward the appropriation of mobile
      phones for mental health monitoring and management. METHODS: We held community
      consultations in Australia consisting of an online survey (n = 525), focus group
      discussions (n = 47), and interviews (n = 20). RESULTS: Respondents used their
      mobile phones daily and predominantly for communication purposes. Of those who
      completed the online survey, the majority (399/525 or 76%) reported that they
      would be interested in using their mobile phone for mental health monitoring and
      self-management if the service were free. Of the 455 participants who owned a
      mobile phone or PDA, there were no significant differences between those who
      expressed interest in the use of mobile phones for this purpose and those who did
      not by gender (chi2(1), = 0.98, P = .32, phi = .05), age group (chi2(4), = 1.95,
      P = .75, phi = .06), employment status (chi2(2), = 2.74, P = .25, phi = .08) or
      marital status (chi2(4), = 4.62, P = .33, phi = .10). However, the presence of
      current symptoms of depression, anxiety, or stress affected interest in such a
      program in that those with symptoms were more interested (chi(2) (1), = 16.67, P
      < .001, phi = .19). Reasons given for interest in using a mobile phone program
      were that it would be convenient, counteract isolation, and help identify
      triggers to mood states. Reasons given for lack of interest included not liking
      to use a mobile phone or technology, concerns that it would be too intrusive or
      that privacy would be lacking, and not seeing the need. Design features
      considered to be key by participants were enhanced privacy and security functions
      including user name and password, ease of use, the provision of reminders, and
      the availability of clear feedback. CONCLUSIONS: Community attitudes toward the
      appropriation of mobile phones for the monitoring and self-management of
      depression, anxiety, and stress appear to be positive as long as privacy and
      security provisions are assured, the program is intuitive and easy to use, and
      the feedback is clear.

PMID- 21169175
TI  - Online alcohol interventions: a systematic review.
AB  - BACKGROUND: There has been a significant increase in the availability of online
      programs for alcohol problems. A systematic review of the research evidence
      underpinning these programs is timely. OBJECTIVES: Our objective was to review
      the efficacy of online interventions for alcohol misuse. Systematic searches of
      Medline, PsycINFO, Web of Science, and Scopus were conducted for English
      abstracts (excluding dissertations) published from 1998 onward. Search terms
      were: (1) Internet, Web*; (2) online, computer*; (3) alcohol*; and (4) E?effect*,
      trial*, random* (where * denotes a wildcard). Forward and backward searches from
      identified papers were also conducted. Articles were included if (1) the primary
      intervention was delivered and accessed via the Internet, (2) the intervention
      focused on moderating or stopping alcohol consumption, and (3) the study was a
      randomized controlled trial of an alcohol-related screen, assessment, or
      intervention. RESULTS: The literature search initially yielded 31 randomized
      controlled trials (RCTs), 17 of which met inclusion criteria. Of these 17
      studies, 12 (70.6%) were conducted with university students, and 11 (64.7%)
      specifically focused on at-risk, heavy, or binge drinkers. Sample sizes ranged
      from 40 to 3216 (median 261), with 12 (70.6%) studies predominantly involving
      brief personalized feedback interventions. Using published data, effect sizes
      could be extracted from 8 of the 17 studies. In relation to alcohol units per
      week or month and based on 5 RCTs where a measure of alcohol units per week or
      month could be extracted, differential effect sizes to posttreatment ranged from
      0.02 to 0.81 (mean 0.42, median 0.54). Pre-post effect sizes for brief
      personalized feedback interventions ranged from 0.02 to 0.81, and in 2 multi
      session modularized interventions, a pre-post effect size of 0.56 was obtained in
      both. Pre-post differential effect sizes for peak blood alcohol concentrations
      (BAC) ranged from 0.22 to 0.88, with a mean effect size of 0.66. CONCLUSIONS: The
      available evidence suggests that users can benefit from online alcohol
      interventions and that this approach could be particularly useful for groups less
      likely to access traditional alcohol-related services, such as women, young
      people, and at-risk users. However, caution should be exercised given the limited
      number of studies allowing extraction of effect sizes, the heterogeneity of
      outcome measures and follow-up periods, and the large proportion of student-based
      studies. More extensive RCTs in community samples are required to better
      understand the efficacy of specific online alcohol approaches, program dosage,
      the additive effect of telephone or face-to-face interventions, and effective
      strategies for their dissemination and marketing.

PMID- 21169176
TI  - How patients with schizophrenia use the internet: qualitative study.
AB  - BACKGROUND: The Internet is an important source of health information for people
      with psychiatric conditions. Little is known about the way patients with
      schizophrenia use the Internet when it comes to issues related to their illness.
      Data on their specific needs, difficulties, and the consequences related to
      Internet use are lacking. OBJECTIVE: Our objective was to investigate the nature
      and subjective consequences of health-related Internet use among patients with
      schizophrenia. METHODS: In all, 26 individual semistructured interviews were
      conducted and analyzed qualitatively in groups of 4 until theoretical saturation
      was achieved. RESULTS: Study results suggest that the Internet is an influential
      source of illness-related information for patients with schizophrenia. Many
      aspects of their behavior around the Internet resemble those of individuals not
      afflicted by mental illness. Importantly, problems specific to patients with
      schizophrenia were stimulus overflow, an inability to deal with the abundance of
      information, difficulties with concentration, lack of energy, paranoid ideas,
      symptom provocation, and the need to distance themselves from illness-related
      topics as part of the recovery process. Internet information was subjectively
      perceived as having the potential to significantly change patients' attitudes
      toward medication and their relationships with doctors. CONCLUSIONS: These
      findings provide insight into how individuals with schizophrenia handle illness
      related Internet information. The data could contribute to the continuous
      development of Internet-based interventions and offer novel approaches to
      optimizing traditional treatment options.

PMID- 21169177
TI  - Theme issue on e-mental health: a growing field in internet research.
AB  - This theme issue on e-mental health presents 16 articles from leading researchers
      working on systems and theories related to supporting and improving mental health
      conditions and mental health care using information and communication
      technologies. In this editorial, we present the background of this theme issue,
      and highlight the content of this issue.

PMID- 21169179
TI  - SPECT/CT fusion imaging integrating anatomy and perfusion of the heart.

PMID- 21169178
TI  - Online group course for parents with mental illness: development and pilot study.
AB  - BACKGROUND: Children of parents with mental illness (COPMI) are at greater risk
      of developing mental disorders themselves. Since impaired parenting skills appear
      to be a crucial factor, we developed a facilitated 8-session preventative group
      course called KopOpOuders (Chin Up, Parents) delivered via the Internet to Dutch
      parents with psychiatric problems. The goal was to promote children's well-being
      by strengthening children's protective factors via their parents. To reach
      parents at an early stage of their parenting difficulties, the course is easily
      accessible online. The course is delivered in a secure chat room, and
      participation is anonymous. OBJECTIVE: This paper reports on (1) the design and
      method of this online the group course and (2) the results of a pilot study that
      assessed parenting skills, parental sense of competence, child well-being, and
      course satisfaction. METHOD: The pilot study had a pre/post design. Parenting
      skills were assessed using Laxness and Overreactivity subscales of the Parenting
      Scale (PS). Sense of parenting competence was measured with the Ouderlijke
      Opvattingen over Opvoeding (OOO) questionnaire, a Dutch scale assessing parental
      perceptions of parenting using the Feelings of Incompetence and Feelings of
      Competence subscales. Child well-being was assessed with the total problem score,
      Emotional Problems, and Hyperactivity subscales of the Strengths and Difficulties
      Questionnaire (SDQ). Paired samples t tests were performed, and Cohen's d was
      used to determine effect sizes. Intention-to-treat analyses and analyses of
      completers only were both performed. Course satisfaction was evaluated using
      custom-designed questionnaires. RESULTS: The sample comprised 48 parents with
      mental illness. The response rate was 100% (48/48) at pretest and 58% (28/48) at
      posttest. Significant improvements were found on PS Laxness and Overreactivity
      subscales (P < .01) and on the OOO Feelings of Incompetence and Competence
      subscales (P < .01) in analysis of completers only as well as by intention-to
      treat analysis. Effects were moderate on the PS (d = .52 and d = .48) and were
      large and moderate on the OOO (d = 0.61 and d = 0.46). At pretest, 75% and 64% of
      PS scores were in the clinical range, which declined to 43% and 39% at posttest.
      No significant changes were found for child well-being. Scores for approximately
      two thirds of children were not in the clinical range at both pretest and
      posttest. The mean course satisfaction score was 7.8 on a 10-point scale. Of all
      participants, 20% (10/48) followed all the sessions. CONCLUSION: This online
      group course on parenting skills is innovative in the field of e-support and
      among interventions for mentally ill parents. The pilot results are promising,
      showing moderate to large effects for parenting skills and parental sense of
      competence. Test scores at baseline indicating parenting problems were largely in
      the clinical range, and baseline scores indicating problems among the children
      were in the nonclinical range, suggesting that parents were reached at an early
      stage. Course satisfaction was high. Future research should focus on cost
      effectiveness and course adherence.

PMID- 21169180
TI  - Do we reperfuse those in most need? Clinical characteristics of ST-elevation
      myocardial infarction patients receiving reperfusion therapy in the countrywide
      registry HELIOS.
AB  - INTRODUCTION: we analysed the clinical profile of patients with an ST-elevation
      myocardial infarction (STEMI) who arrived in hospital within 12 hrs from pain
      onset and either received reperfusion therapy (PCI or fibrinolytic therapy) or
      remained without reperfusion. METHODS: the Hellenic Infarction Observation Study
      (HELIOS) was a countrywide registry of acute myocardial infarction, conducted
      during 2005-2006. The registry enrolled 1840 patients with myocardial infarction
      from 31 hospitals, with a proportional representation of all types of hospitals
      and all geographical areas. RESULTS: of 870 patients with STEMI who were admitted
      within 12 hrs from pain onset, Group A received no reperfusion (n=289, 33.2%),
      group B underwent primary PCI (n=84, 9.7%) and group C received fibrinolysis
      (n=497, 57.1%). In groups A, B and C, respectively, mean age was 73 +/- 13, 61 +/
      12 and 62 +/- 13 years (p<0.001). The prevalence of female sex was 33%, 14%,
      18%, of diabetes 40%, 23%, 21%, of prior MI 23%, 10%, 11% and of Killip class 2-4
      at admission 32%, 11%, 13%, respectively (all p<0.001). In a multivariate
      analysis, advanced Killip class, age, diabetes and pain to admission time >3 hrs
      were all independent variables related to no reperfusion therapy. CONCLUSION:
      reperfusion therapies are applied to relatively lower-risk patients. If a
      survival advantage is to be expected at the national level, more high-risk
      patients, such as the elderly, women, diabetics, and mainly those with advanced
      Killip class, should be considered for reperfusion strategies.

PMID- 21169181
TI  - Transcatheter aortic valve implantation, patient selection process and procedure:
      two centres' experience of the intervention without general anaesthesia.
AB  - INTRODUCTION: transcatheter aortic valve implantation (TAVI) is an emerging
      technique for the treatment of aortic stenosis. With the advent of percutaneous
      suture devices for the access point and prosthesis delivery systems of smaller
      diameter, TAVI has become a truly percutaneous procedure: percutaneous aortic
      valve replacement (PAVR). Thus, PAVR may be conducted without general anaesthesia
      (GA). METHODS: We report two centres' experience from PAVR without GA. CoreValve
      aortic bioprostheses were utilised. The patient selection process and PAVR
      procedure are described in detail. RESULTS: a total of 30 patients (pts) were
      treated with PAVR. In 4 pts correction of the initial malposition of the
      prosthesis required a special technique (2 pts: "snare"; 2 pts: "removing and
      reinserting"). At 1-month follow up, haemodynamic and clinical improvements were
      observed: left ventricular ejection fraction increased from 50.8 +/- 9.3% to 54.3
      +/- 8.3% (p=0.02); peak aortic valve gradient decreased from 90.3 +/- 26.4 mmHg
      to 14.8 +/- 9.7 mmHg, (p<0.001); NYHA functional class decreased from 3.53 +/-
      0.93 to 1.45 +/- 0.94 (p<0.001). Overall 1-month mortality was 3.3% (1 patient
      died). CONCLUSION: PAVR without general anaesthesia is a feasible technique,
      however the role of anaesthesiologists is still important.

PMID- 21169182
TI  - Effect of aortic stiffness on left ventricular long-axis systolic function in
      adults with Marfan syndrome.
AB  - INTRODUCTION: several studies have documented increased aortic stiffness in
      patients with Marfan syndrome (MFS) using echocardiography and magnetic resonance
      imaging. Recent studies have also shown primary myocardial impairment in MFS. We
      investigated whether left ventricular (LV) function could be further impaired
      when acting against a stiff vascular system. METHODS: twenty-six MFS patients
      (mean age 30 +/- 2 years, 17 males) and 30 normal controls were examined. Mitral
      annular displacement, as a surrogate for LV systolic function, was evaluated from
      septal, anterolateral, anterior and inferior regions using M-mode and tissue
      Doppler imaging. Septal/anterolateral and anterior/inferior M-mode displacement
      measurements were normalised by dividing them by the longitudinal inner distance
      obtained at end diastole from the 4- and 2-chamber views, respectively. Carotid
      femoral and carotid-radial (CF and CR) pulse wave velocities (PWV) were
      determined using an automated applanation tonometry device. Central aortic
      pressure was assessed by recording radial waveforms with the tonometer and
      central waveforms were reconstructed using a generalised transfer function.
      RESULTS: CF- and CR-PWV were significantly increased in the patient group
      (p<0.001), whilst mitral annular displacement measurements were significantly
      reduced (p<0.001, all regions). Regression analysis demonstrated that the disease
      status and CF-PWV were strongly associated with reduced LV systolic function
      (p<0.001, p=0.002, respectively). CONCLUSIONS: our study showed reduced LV
      systolic function and increased aortic stiffness in MFS patients. The efficiency
      of a fibrillin-1 deficient heart may be further reduced by ejection into a stiff
      vascular system. Care should be taken to ensure that any treatment regime
      addresses both increased aortic stiffness and myocardial dysfunction in MFS.

PMID- 21169183
TI  - The ever increasing role of percutaneous interventions in coronary
      revascularisation.

PMID- 21169184
TI  - Diagnostic modalities of the most common forms of secondary hypertension.

PMID- 21169185
TI  - Recommendations for the cardiovascular screening of athletes.

PMID- 21169186
TI  - Fungal endocarditis of the superior vena cava: the role of transesophageal
      echocardiography.

PMID- 21169187
TI  - Additional help to diagnose functionally significant left main coronary artery
      stenosis: doppler echocardiography.
AB  - Doppler echocardiography is a widely used non-invasive method for the evaluation
      of coronary flow velocities and reserve. We report a case that demonstrates the
      possible additive role of transthoracic echocardiography (TTE) in the diagnosis
      of significant left main coronary artery (LM) stenosis in a chest pain patient.
      Coronary angiography showed no significant LM stenosis. During TTE with pulsed
      Doppler measurements, a significant increase in coronary flow velocities could be
      demonstrated in the distal LM. Intravascular ultrasound confirmed a significant
      soft plaque in the distal LM. The present case suggests that Doppler TTE may have
      an additional role in the diagnosis of significant LM stenosis in symptomatic
      patients. A colour Doppler flow acceleration with high velocities in the LM could
      raise the suspicion of significant LM stenosis, even if the stenosis cannot be
      detected by standard coronary angiography.

PMID- 21169188
TI  - Low back pain following intravenous administration of amiodarone.
AB  - Amiodarone is a widely used antiarrhythmic drug whose use is significantly
      limited by numerous undesirable effects following long-term administration. In
      the literature so far, it has been reported that the most common acute adverse
      effect of the intravenous administration of amiodarone requiring intervention is
      hypotension. We present the case of a female patient who experienced low back
      pain after an intravenous loading dose of amiodarone.

PMID- 21169189
TI  - Differential diagnosis of a left atrial mass: role of three-dimensional
      transoesophageal echocardiography.
AB  - We describe an 81-year-old woman with an episode of loss of consciousness and a
      mass inside the left atrium. We demonstrate the added value of three-dimensional
      transoesophageal echocardiography in the differential diagnosis of the cardiac
      masses.

PMID- 21169190
TI  - Left ventricular assist device vegetation: "cure" without device explantation.
AB  - Infection following the implantation of a left ventricular assist device (LVAD)
      is a life-threatening complication with mortality rates ranging from 15% to 44%.
      Staphylococcus aureus and Staphylococcus epidermidis are the most frequently
      identified pathogens and are responsible for 60% of LVAD-related infections,
      local as well as systemic. In this report we describe the successful therapeutic
      management of a patient who received a Heart Mate II as "bridging-to-recovery",
      which was complicated by device infection that was managed without device
      explantation.

PMID- 21169191
TI  - An interesting case of cardiac amyloidosis initially diagnosed as hypertrophic
      cardiomyopathy.
AB  - Cardiac involvement occurs frequently in primary amyloidosis and is associated
      with heart failure hospitalizations and poor survival. The initial presentation
      of the disease may be misleading, resulting in under-diagnosis of cardiac
      amyloidosis and late initiation of treatment. We present a case of cardiac
      amyloidosis initially misdiagnosed as hypertrophic cardiomyopathy and we discuss
      the key findings of the disease along with the latest evidence regarding the
      management and prognosis of cardiac amyloidosis.

PMID- 21169192
TI  - Tachycardia induction due to inappropriate implantable cardioverter defibrillator
      therapy: what is the mechanism?
AB  - Antitachycardia therapies administered by implantable cardioverter defibrillators
      (ICDs) can occasionally prove proarrhythmic due to induction of ventricular
      tachyarrhythmias. In this report we present the case of a tachycardia induction
      as a result of inappropriate therapy delivery in an ICD recipient. Detailed
      analysis of the stored electrograms facilitated the delineation of the underlying
      mechanism of the recorded tachycardia.

PMID- 21169193
TI  - Atypical Brugada ECG phenotype involving ST-segment elevation in lateral leads.

PMID- 21169195
TI  - Cardiovascular medicine in Greece: an appraisal of conditions today and future
      prospects.

PMID- 21169194
TI  - Creation of a congress centre in Greece.

PMID- 21169196
TI  - Repeated local implantation of autologous peripheral blood mononuclear cells for
      the treatment of ischaemic digits in patients with connective tissue diseases.
AB  - OBJECTIVES: Blood flow in fingers and toes is often impaired in patients with
      CTDs, mandating amputation in some. Our previous study showed that a single
      implantation of autologous bone marrow cells is as effective as peripheral blood
      mononuclear cells (MNCs) to restore impaired blood flow, although neither has
      long-lasting efficacy. In this study, autologous peripheral blood MNCs were
      implanted repeatedly to evaluate a better efficacy. METHODS: Three patients with
      SSc, two with microscopic polyangiitis and one with MCTD were enrolled. All
      patients had severe RP, ulcers and/or necrosis in the extremities. MNCs were
      obtained from 400 to 1600 ml of peripheral blood and implanted into 20-80
      different sites in the palms and/or soles. This procedure was repeated every 3
      months up to 1 year. Humoral factors were measured by ELISAs. RESULTS: Visual
      analogue scale scores for pain, coldness and subjective satisfaction were
      improved after implantation in all patients. Pre-treatment ulcers in five
      patients were cured after repeated implantations. Angiography showed increased
      vasculature compared with baseline. Serum levels of VEGF increased after
      implantation, whereas levels of IL-1beta, fibroblast growth factor and endostatin
      had variable results. None of the patients had any adverse reactions during a
      follow-up period of up to 3 years. CONCLUSIONS: Repeated implantation of
      peripheral blood MNCs was effective and safe for the treatment of recalcitrant
      ulcers developing in ischaemic digits and toes in patients with CTD.

PMID- 21169197
TI  - Inhibition of iron absorption by polyphenols as an anti-cancer mechanism.

PMID- 21169199
TI  - Towards a genome-wide transcriptogram: the Saccharomyces cerevisiae case.
AB  - Analysis of genome-wide expression data poses a challenge to extract relevant
      information. The usual approaches compare cellular expression levels relative to
      a pre-established control and genes are clustered based on the correlation of
      their expression levels. This implies that cluster definitions are dependent on
      the cellular metabolic state, eventually varying from one experiment to another.
      We present here a computational method that order genes on a line and clusters
      genes by the probability that their products interact. Protein-protein
      association information can be obtained from large data bases as STRING. The
      genome organization obtained this way is independent from specific experiments,
      and defines functional modules that are associated with gene ontology terms. The
      starting point is a gene list and a matrix specifying interactions. Considering
      the Saccharomyces cerevisiae genome, we projected on the ordering gene expression
      data, producing plots of transcription levels for two different experiments,
      whose data are available at Gene Expression Omnibus database. These plots
      discriminate metabolic cellular states, point to additional conclusions, and may
      be regarded as the first versions of 'transcriptograms'. This method is useful
      for extracting information from cell stimuli/responses experiments, and may be
      applied with diagnostic purposes to different organisms.

PMID- 21169201
TI  - Getting the aorta pants in place: a 'community of guidance' in the evolving
      practice of vascular implant surgery.
AB  - The evolving nature of surgical treatments creates gaps between evidence-based
      guidelines and actual clinical practice.This article addresses the emerging
      clinical practice of the EndoVascular Aneurysm Repair (EVAR), a surgical
      treatment of patients with Abdominal Aortic Aneurysm (AAA). Drawing on a
      qualitative study across three hospitals, we identified three interplaying
      expertise traits: the collective, the interpersonal and the technical, each being
      present to promote surgical work. The evolvement of EVAR is contextualized within
      technical artefacts and patient characteristics, along with a joint decision
      approach. The intertwinement between various expertise traits and contextual
      factors forms a 'community of guidance', nourishing further EVAR innovation
      without formalized institutions, evidence, training or guidelines. However, the
      lack of a shared context limits the transfer of evolving knowledge across
      hospital boundaries.

PMID- 21169200
TI  - Trans-biopolitics: Complexity in interspecies relations.
AB  - This article introduces the concept of trans-biopolitics to account for
      complexity in the intermingling of animal and human bodies, with particular
      attention to diseases capable of crossing the species divide from animals to
      humans. While zoonotic diseases never disappeared, they had re-emerged as
      pressing concerns by the 21st century. The concept of trans-biopolitics takes
      into account the power relations inherent in human and nonhuman lives in
      contemporary global, industrial, and technological formations. More specifically,
      trans-biopolitics revolves around practices determining whose lives are possible
      or legitimate to prolong, whose bodies are sacrificed in order to preserve the
      vitality of other bodies, and whose bodies are sustained yet ultimately rendered
      insignificant. To illustrate, we examine connections between bovine spongiform
      encephalopathy and feline spongiform encephalopathy, to show how certain bodies
      (humans, livestock) are taken into consideration in terms of health and food
      regulations, whereas other bodies (pets) remain at the periphery. Acknowledging
      human-animal relations in contemporary technological and global contexts
      challenges us to rethink ways in which the politics of health continues to
      evolve.

PMID- 21169202
TI  - 'The black dog just came and sat on my face and built a kennel': Gay men making
      sense of 'depression'.
AB  - This article reports on in-depth interviews with gay men about their experiences
      and understanding of depression. It is a key outcome of the collaboration between
      social researchers, general practitioners and community partners to investigate
      the management of depression in gay men in primary care settings. As part of the
      qualitative arm of the project in-depth interviews were conducted with 40 gay men
      in Sydney and Adelaide (Australia). The approach to discourse analysis is
      informed by Hallidayan systemic functional linguistics. Six constructions of
      depression were identified: (1) depression as a constellation of symptoms; (2)
      symptoms constructed as experience; (3) depression as agent; (4) depression as
      mental processes; (5) not meeting social expectations; and (6) engaging with
      psychiatric discourse: constructing alternative positions. Gay men draw on the
      biomedical model of depression as low mood and loss of pleasure as well as on
      constructions of depression in terms of social experience. The biomedical model
      of depression is, however, not positioned as unproblematic. Rather, gay men align
      or disalign with this discourse according to their own experience, thereby
      enacting diverse masculinities. Gay men's discourses of depression are
      inextricably linked to the community activism of gay men and their community
      organizations in the context of the HIV epidemic, as well as a synergy between
      gay men and their doctors.

PMID- 21169203
TI  - Frailty, disability and old age: a re-appraisal.
AB  - Frailty has become a topic of increasing interest in health care. No longer
      treated as a catch-all term for agedness, decline and disablement it has acquired
      a more precise definition, applied to those individuals whose 'aged' state is
      seen to put them at risk of adverse outcomes. This transformation is we argue the
      outcome of a more general differentiation of terms that were previously used to
      categorize the weak and marginal within society. Old age re-labelled as 'later
      life' has become re-articulated as a successful life stage relatively free from
      impairment. Disability has been re-positioned and its links with impairment
      attenuated while chronic illness has acquired a new narrative of its own. This
      has left frailty behind, redolent still with all the old negative attributes of
      marginality, but now more than ever evacuated of any remaining elements of
      'status' or 'agency'. Frailty is defined less by the identities of those who are
      deemed frail than by what frailty seems to augur in its direction of travel - a
      journey towards unspecified adverse outcomes. This re-positioning, we suggest,
      helps lay the foundation of a social imaginary of 'the fourth age' as the new
      location of old age.

PMID- 21169204
TI  - Professionalization and its discontents.
AB  - The sociology of professions has generally considered professionalization as a
      desirable outcome for occupational groups. This case study of professionalization
      in the UK National Health Service, based on an analysis of documents, presents a
      challenge to that view. For many groups, the state is now so comprehensively
      dominant in the process of professionalization that it can effectively dictate
      professional status on its own terms. Many of the advantages that accrued to
      professions that developed historically will not be available to groups that
      professionalize under this new regime. Though elite groups within the profession
      studied (Operating Department Practice) were strongly in favour of
      professionalization, throughout the process there were also dissenting voices.
      This case study will show how professionalization, despite being described as the
      'Holy Grail' by those in favour of it, turned out to be, at best, a mixed
      blessing. While medicine may still be able to negotiate with the state for other
      groups, professionalization can in the future be equated with regulation.

PMID- 21169205
TI  - Braving a faceless new world? Conceptualizing trust in the pharmaceutical
      industry and its products.
AB  - Pharmaceutical products are commonly relied upon by professionals, and
      correspondingly patients, within a wide range of healthcare contexts. This
      dependence, combined with the inherent risk and uncertainty surrounding both
      medical practice and the drugs it harnesses, points towards the importance of
      trust in the pharmaceutical industry--a subject which has been much neglected by
      researchers. This article begins to address this deficiency by mapping out a
      conceptual framework which may form a useful basis for future research into this
      important topic. The often negative portrayal of the pharmaceutical industry in
      the public sphere belies a state of apparent confidence in its products. The role
      of prescribing professionals as 'mediators of trust' amid a faceless system of
      production and, alongside regulators, as bases of assurance in the quality of
      drugs goes some way towards explaining this contradiction. Recent policy moves
      towards fostering increased patient 'expertise' and responsibility for illness
      management, a widening of over-the-counter medication availability and a growing
      market of products (mainstream and illicit) via the Internet suggest this role of
      'facework' in facilitating trust may be becoming more marginal. This heightened
      requirement for trusting amid the unfamiliar, and an apparent willingness to do
      so, underlines the need for further research into trust in the industry--both
      mainstream and underground--and its products. Within this discussion an agenda
      for furthering our understandings of the political-economy of the pharmaceutical
      industry becomes apparent, one which might be most effectively approached by way
      of a broader political-economy of hope and trust.

PMID- 21169198
TI  - Insights into the evolution of Archaea and eukaryotic protein modifier systems
      revealed by the genome of a novel archaeal group.
AB  - The domain Archaea has historically been divided into two phyla, the
      Crenarchaeota and Euryarchaeota. Although regarded as members of the
      Crenarchaeota based on small subunit rRNA phylogeny, environmental genomics and
      efforts for cultivation have recently revealed two novel phyla/divisions in the
      Archaea; the 'Thaumarchaeota' and 'Korarchaeota'. Here, we show the genome
      sequence of Candidatus 'Caldiarchaeum subterraneum' that represents an
      uncultivated crenarchaeotic group. A composite genome was reconstructed from a
      metagenomic library previously prepared from a microbial mat at a geothermal
      water stream of a sub-surface gold mine. The genome was found to be clearly
      distinct from those of the known phyla/divisions, Crenarchaeota
      (hyperthermophiles), Euryarchaeota, Thaumarchaeota and Korarchaeota. The unique
      traits suggest that this crenarchaeotic group can be considered as a novel
      archaeal phylum/division. Moreover, C. subterraneum harbors an ubiquitin-like
      protein modifier system consisting of Ub, E1, E2 and small Zn RING finger family
      protein with structural motifs specific to eukaryotic system proteins, a system
      clearly distinct from the prokaryote-type system recently identified in Haloferax
      and Mycobacterium. The presence of such a eukaryote-type system is unprecedented
      in prokaryotes, and indicates that a prototype of the eukaryotic protein modifier
      system is present in the Archaea.

PMID- 21169206
TI  - It's not fair: an Interpretative Phenomenological Analysis of discourses of
      justice and fairness in chronic pain.
AB  - Quantitative research suggests that perceiving injustice can impact negatively
      upon physical and psychological health in chronic pain. However, little is known
      about the experience and perceptions of injustice in this context. This study
      examines the phenomenology of justice and injustice in chronic pain. Fifteen
      chronic pain sufferers recruited from General Practices in upper, middle and
      lower socioeconomic areas participated in one of three focus group discussions.
      Semi-structured interviews were conducted to interrogate justice-related
      conceptions. All discussions were observed, audio-recorded, transcribed verbatim
      and subjected to Interpretative Phenomenological Analysis. The dominant theme of
      the upper socioeconomic group was 'seeking equality'. For the middle
      socioeconomic group the dominant theme was 'battle for quality of life' and for
      the lower socioeconomic group the dominant theme was 'the unfair advantage of
      others'. It is concluded that this group of chronic pain sufferers prioritize
      justice-related issues in terms of what is dominant to their social concerns and
      personal needs.

PMID- 21169207
TI  - How far can Foucault take us?: an analysis of the changing discourses and
      limitations of the medical treatment of apoplexy and stroke.
AB  - This article examines the conditions under which epistemological shifts in
      medicine have shaped the history of apoplexy and stroke. Our intention is to
      understand how stroke medicine as a distinct branch of bio-medicine has emerged
      in its current form. In doing so, we draw on aspects of the work of Michel
      Foucault as they relate to fabrication of biomedical discourses. The past 300
      years of the transformation of the condition is examined using Michel Foucault's
      analysis of medical history as instances of the changing spatialization of
      disease. While the adoption of this approach helped explain how medical practice
      was shaped by changing interpretations of the causes of apoplexy and stroke over
      the past few centuries, we also found that there were certain limitations to such
      an approach. Overall, however, we hope to show that an examination of the history
      of stroke medicine through a Foucauldian influenced lens can provide a useful
      understanding of its current circumstances as well as throw light on gaps in
      Foucauldian approaches themselves.

PMID- 21169208
TI  - Determinants of physician utilization, emergency room use, and hospitalizations
      among populations with multiple health vulnerabilities.
AB  - Understanding the factors that influence differing types of health care
      utilization within vulnerable groups can serve as a basis for projecting future
      health care needs, forecasting future health care expenditures, and influencing
      social policy. In this article the Behavioral Model for Vulnerable Populations is
      used to evaluate discretionary (physician visits) and non-discretionary
      (emergency room visits, and hospitalizations) health utilization patterns of a
      sample of 1466 respondents with one or more vulnerable health classification.
      Reported vulnerabilities include: (1) persons with substance disorders; (2)
      homeless persons; (3) persons with mental health problems; (4) victims of violent
      crime; (5) persons diagnosed with HIV/AIDS; (6) and persons in receipt of public
      benefits. Hierarchical logistic regression is used on three nested models to
      model factors that influence physician visits, emergency room visits, and
      hospitalizations. Additionally, bivariate logistic regression analyses are
      completed using a vulnerability index to evaluate the impact of increased numbers
      of vulnerability on all three forms of health care utilization. Findings from
      this study suggest the Behavioral Model of Vulnerable Populations be employed in
      future research regarding health care utilization patterns among vulnerable
      populations. This article encourages further research investigating the
      cumulative effect of health vulnerabilities on the use of non-discretionary
      services so that this behavior could be better understood and appropriate social
      policies and behavioral interventions implemented.

PMID- 21169209
TI  - 'The family is part of the treatment really': a qualitative exploration of
      collective health narratives in families.
AB  - Clinicians are increasingly asking questions about family history to inform
      decision making, but the quality of decisions rests on the quality of information
      provided by the patient. In families with genetically transmitted diseases,
      research has found a strong collective understanding of inheritance and risk,
      developed through constant communication between family members. Here, we explore
      whether there are similar processes in families with more common conditions like
      heart disease, asthma or osteo-arthritis. From in-depth interviews with lay
      people, we found that families created a culture of 'health talk', especially
      between sisters. Caring for other family members was demonstrated through sharing
      vital health information; on the other hand care could be shown by not worrying
      family members by talking about possibly inherited illness. Patterns of
      inheritance and health were talked about in participants' families (resemblance,
      similar conditions and affected body areas). From these, a picture developed of
      what the family was 'like' in health terms. Overall, experiential knowledge and
      family narrative was interwoven with expert discourse to form a complex
      understanding of medical family histories.

PMID- 21169210
TI  - Embodying occupational overuse syndrome.
AB  - This article explores the ways in which embodiedness has become problematic for
      New Zealand sufferers of occupational overuse syndrome (OOS). While successful
      rehabilitation could lead back to employment, this was based on the biographical
      continuity of a bodily hexus that ignored persistent pain. The reality of OOS
      involved a liminal fragility associated with social isolation, loss of
      identities, pain and functional disability that was incorporated into re
      negotiated identities and biographies with the result that respondents became
      exquisitely self-absorbed, exercising constant bodily surveillance and discipline
      in order to manage their symptoms.

PMID- 21169212
TI  - Deletions and recombinations with the RNA1 3' ends of different tobraviruses have
      created a multitude of tobacco rattle virus TCM-related RNA2 species in
      Alstroemeria and tulip.
AB  - In vegetatively propagated Alstroemeria plants that showed pronounced stunting
      and necrotic leaf spots, a tobravirus infection was diagnosed in which one
      tobacco rattle virus (TRV, strain AL) RNA1 species was associated with seven
      different RNA2 species. The latter differed considerably in size and in the types
      of their 3' RNA1-related sequences. The 5' RNA2-specific part of all these RNA2
      molecules showed almost 100% sequence identity with that of RNA2 of the TRV
      isolate TCM from tulip, but in some of these RNA2 molecules it was shorter than
      in the TCM isolate, whereas in others it was longer. One of the TRV AL RNA2
      molecules, i.e. TC3'PE-a, contained the full set of three full-length RNA2
      specific ORFs (ORF2a, -2b and -2c), whereas the previously analysed TCM sequence
      contained only ORF2a and -2b. In four of these TRV AL RNA2 molecules, i.e. those
      that had a relatively short RNA2-specific part, the 3' end was identical to that
      of the cognate TRV AL RNA1, but in the other three, which had a long RNA2
      specific part, it was closely related to that of pea early browning virus (PEBV)
      RNA1, which was not detected in the infected plants. A comparison with previously
      described TRV/PEBV RNA2 recombinants suggested that the various TRV AL RNA2
      molecules may represent various steps and side steps in an evolutionary process,
      which is apt to open the wide host range of TRV also to PEBV-derived RNA2
      species.

PMID- 21169213
TI  - Evolution of cassava brown streak disease-associated viruses.
AB  - Cassava brown streak disease (CBSD) has occurred in the Indian Ocean coastal
      lowlands and some areas of Malawi in East Africa for decades, and makes the
      storage roots of cassava unsuitable for consumption. CBSD is associated with
      Cassava brown streak virus (CBSV) and the recently described Ugandan cassava
      brown streak virus (UCBSV) [picorna-like (+)ssRNA viruses; genus Ipomovirus;
      family Potyviridae]. This study reports the first comprehensive analysis on how
      evolution is shaping the populations of CBSV and UCBSV. The complete genomes of
      CBSV and UCBSV (four and eight isolates, respectively) were 69.0-70.3 and 73.6
      74.4% identical at the nucleotide and polyprotein amino acid sequence levels,
      respectively. They contained predictable sites of homologous recombination,
      mostly in the 3'-proximal part (NIb-HAM1h-CP-3'-UTR) of the genome, but no
      evidence of recombination between the two viruses was found. The CP-encoding
      sequences of 22 and 45 isolates of CBSV and UCBSV analysed, respectively, were
      mainly under purifying selection; however, several sites in the central part of
      CBSV CP were subjected to positive selection. HAM1h (putative nucleoside
      triphosphate pyrophosphatase) was the least similar protein between CBSV and
      UCBSV (aa identity approx. 55%). Both termini of HAM1h contained sites under
      positive selection in UCBSV. The data imply an on-going but somewhat different
      evolution of CBSV and UCBSV, which is congruent with the recent widespread
      outbreak of UCBSV in cassava crops in the highland areas (>1000 m above sea
      level) of East Africa where CBSD has not caused significant problems in the past.

PMID- 21169215
TI  - Induction of mucosal and systemic antibody and T-cell responses following prime
      boost immunization with novel adjuvanted human immunodeficiency virus-1-vaccine
      formulations.
AB  - As sexual transmission of human immunodeficiency virus-1 (HIV-1) occurs via the
      mucosa, an ideal HIV-1 vaccine should induce both mucosal and systemic immunity.
      We therefore sought to evaluate the induction of mucosal responses using a DNA
      env prime-gp120 protein boost approach in which sequential nasal and parenteral
      protein administration was performed with two novel carbohydrate-based adjuvants.
      These adjuvants, Advax-M and Advax-P, were specifically designed for mucosal and
      systemic immune enhancement, respectively. Murine intranasal immunization with
      gp120/Advax-M adjuvant elicited gp120-specific IgA in serum and mucosal
      secretions that was markedly enhanced by DNA priming. Boosting of DNA-primed mice
      with gp120/Advax-M and gp120/Advax-P by sequential intranasal and intramuscular
      immunization, or vice versa, elicited persistent mucosal gp120-specific IgA,
      systemic IgG and memory T- and B-cell responses. Induction of homologous, but not
      heterologous, neutralizing activity was noted in the sera of all immunized
      groups. While confirmation of efficacy is required in challenge studies using non
      human primates, these results suggest that the combination of DNA priming with
      sequential nasal and parenteral protein boosting, with appropriate mucosal and
      systemic adjuvants, could generate strong mucosal and systemic immunity and may
      block HIV-1 mucosal transmission and infection.

PMID- 21169216
TI  - Multinodal regulation of the arcuate/paraventricular nucleus circuit by leptin.
AB  - Melanocortin-4 receptor (MC4R) is critical for energy homeostasis, and the
      paraventricular nucleus of the hypothalamus (PVN) is a key site of MC4R action.
      Most studies suggest that leptin regulates PVN neurons indirectly, by binding to
      receptors in the arcuate nucleus or ventromedial hypothalamus and regulating
      release of products like alpha-melanocyte-stimulating hormone (alpha-MSH),
      neuropeptide Y (NPY), glutamate, and GABA from first-order neurons onto the MC4R
      PVN cells. Here, we investigate mechanisms underlying regulation of activity of
      these neurons under various metabolic states by using hypothalamic slices from a
      transgenic MC4R-GFP mouse to record directly from MC4R neurons. First, we show
      that in vivo leptin levels regulate the tonic firing rate of second-order MC4R
      PVN neurons, with fasting increasing firing frequency in a leptin-dependent
      manner. We also show that, although leptin inhibits these neurons directly at the
      postsynaptic membrane, alpha-MSH and NPY potently stimulate and inhibit the
      cells, respectively. Thus, in contrast with the conventional model of leptin
      action, the primary control of MC4R PVN neurons is unlikely to be mediated by
      leptin action on arcuate NPY/agouti-related protein and proopiomelanocortin
      neurons. We also show that the activity of MC4R PVN neurons is controlled by the
      constitutive activity of the MC4R and that expression of the receptor mRNA and
      alpha-MSH sensitivity are both stimulated by leptin. Thus, leptin acts
      multinodally on arcuate nucleus/PVN circuits to regulate energy homeostasis, with
      prominent mechanisms involving direct control of both membrane conductances and
      gene expression in the MC4R PVN neuron.

PMID- 21169217
TI  - Saccharides enhance iron bioavailability to Southern Ocean phytoplankton.
AB  - Iron limits primary productivity in vast regions of the ocean. Given that marine
      phytoplankton contribute up to 40% of global biological carbon fixation, it is
      important to understand what parameters control the availability of iron (iron
      bioavailability) to these organisms. Most studies on iron bioavailability have
      focused on the role of siderophores; however, eukaryotic phytoplankton do not
      produce or release siderophores. Here, we report on the pivotal role of
      saccharides--which may act like an organic ligand--in enhancing iron
      bioavailability to a Southern Ocean cultured diatom, a prymnesiophyte, as well as
      to natural populations of eukaryotic phytoplankton. Addition of a monosaccharide
      (>2 nM of glucuronic acid, GLU) to natural planktonic assemblages from both the
      polar front and subantarctic zones resulted in an increase in iron
      bioavailability for eukaryotic phytoplankton, relative to bacterioplankton. The
      enhanced iron bioavailability observed for several groups of eukaryotic
      phytoplankton (i.e., cultured and natural populations) using three saccharides,
      suggests it is a common phenomenon. Increased iron bioavailability resulted from
      the combination of saccharides forming highly bioavailable organic associations
      with iron and increasing iron solubility, mainly as colloidal iron. As
      saccharides are ubiquitous, present at nanomolar to micromolar concentrations,
      and produced by biota in surface waters, they also satisfy the prerequisites to
      be important constituents of the poorly defined "ligand soup," known to weakly
      bind iron. Our findings point to an additional type of organic ligand,
      controlling iron bioavailability to eukaryotic phytoplankton--a key unknown in
      iron biogeochemistry.

PMID- 21169211
TI  - Evolution and structure of Tomato spotted wilt virus populations: evidence of
      extensive reassortment and insights into emergence processes.
AB  - Tomato spotted wilt virus (TSWV; genus Tospovirus, family Bunyaviridae) genetic
      diversity was evaluated by sequencing parts of the three RNA genome segments of
      224 isolates, mostly from pepper and tomato crops in southern Europe. Eighty
      three per cent of the isolates showed consistent clustering into three clades,
      corresponding to their geographical origin, Spain, France or the USA, for the
      three RNA segments. In contrast, the remaining 17% of isolates did not belong to
      the same clade for the three RNA segments and were shown to be reassortants.
      Among them, eight different reassortment patterns were observed. Further
      phylogenetic analyses provided insights into the dynamic processes of the
      worldwide resurgence of TSWV that, since the 1980s, has followed the worldwide
      dispersal of the western flower thrips (Frankliniella occidentalis) tospovirus
      vector. For two clades composed essentially of Old World (OW) isolates, tree
      topology suggested a local re-emergence of indigenous TSWV populations following
      F. occidentalis introductions, while it could not be excluded that the ancestors
      of two other OW clades were introduced from North America contemporarily with F.
      occidentalis. Finally, estimation of the selection intensity that has affected
      the evolution of the NSs and nucleocapsid proteins encoded by RNA S of TSWV
      suggests that the former could be involved in the breakdown of resistance
      conferred by the Tsw gene in pepper.

PMID- 21169219
TI  - Completely phased genome sequencing through chromosome sorting.
AB  - The two haploid genome sequences that a person inherits from the two parents
      represent the most fundamentally useful type of genetic information for the study
      of heritable diseases and the development of personalized medicine. Because of
      the difficulty in obtaining long-range phase information, current sequencing
      methods are unable to provide this information. Here, we introduce and show
      feasibility of a scalable approach capable of generating genomic sequences
      completely phased across the entire chromosome.

PMID- 21169220
TI  - Reiterative AP2a activity controls sequential steps in the neural crest gene
      regulatory network.
AB  - The neural crest (NC) emerges from combinatorial inductive events occurring
      within its progenitor domain, the neural border (NB). Several transcription
      factors act early at the NB, but the initiating molecular events remain elusive.
      Recent data from basal vertebrates suggest that ap2 might have been critical for
      NC emergence; however, the role of AP2 factors at the NB remains unclear. We show
      here that AP2a initiates NB patterning and is sufficient to elicit a NB-like
      pattern in neuralized ectoderm. In contrast, the other early regulators do not
      participate in ap2a initiation at the NB, but cooperate to further establish a
      robust NB pattern. The NC regulatory network uses a multistep cascade of secreted
      inducers and transcription factors, first at the NB and then within the NC
      progenitors. Here we report that AP2a acts at two distinct steps of this cascade.
      As the earliest known NB specifier, AP2a mediates Wnt signals to initiate the NB
      and activate pax3; as a NC specifier, AP2a regulates further NC development
      independent of and downstream of NB patterning. Our findings reconcile
      conflicting observations from various vertebrate organisms. AP2a provides a
      paradigm for the reiterated use of multifunctional molecules, thereby
      facilitating emergence of the NC in vertebrates.

PMID- 21169222
TI  - Defining profiles of functional limitations in groups of older persons: how and
      why?
AB  - OBJECTIVE: Addressing the complexity of multiple health problems in the older
      population, the objective was to identify combinations of functional limitations
      for use in simulation analysis, to enable predictions of the potentially most
      severe person-environment fit (i.e., accessibility) problems among groups of
      older persons. METHOD: Utilizing data from 1,542 persons aged 75 to 89 years and
      applying Configuration Frequency Analysis, we tested which combinations of
      functional limitations that occurred more or less often than expected.
      Significant combinations were defined as type profiles and used in simulated
      accessibility analyses. RESULTS: Eleven combinations occurred more often and
      eight less often than expected (p < .05). Simulations with ten type profiles
      predicted varied patterns of accessibility problems. CONCLUSION: The use of type
      profiles has potential to contribute to the knowledge of combinations of
      functional limitations among groups of older persons. Variation in predicted
      accessibility problems for different type profiles helps identifying priorities
      in societal planning.

PMID- 21169223
TI  - The objective impact of clinical peer review on hospital quality and safety.
AB  - Despite its importance, the objective impact of clinical peer review on the
      quality and safety of care has not been studied. Data from 296 acute care
      hospitals show that peer review program and related organizational factors can
      explain up to 18% of the variation in standardized measures of quality and
      patient safety. The majority of programs rely on an outmoded and dysfunctional
      process model. Adoption of best practices informed by the continuing study of
      peer review program effectiveness has the potential to significantly improve
      patient outcomes.

PMID- 21169224
TI  - Chylomicron remnants and nonesterified fatty acids differ in their ability to
      inhibit genes involved in lipogenesis in rats.
AB  - Primary hepatocytes treated with nonesterified PUFA have been used as a model for
      analyzing the inhibitory effects of dietary polyunsaturated fats on lipogenic
      gene expression. Although nonesterified fatty acids play an important signaling
      role in starvation, they do not completely recapitulate the mechanism of dietary
      fat presentation to the liver, which is delivered via chylomicron remnants. To
      test the effect of remnant TG on lipogenic enzyme expression, chylomicron
      remnants were generated from the lymph of rats intubated with either safflower
      oil or lard. The remnants were added to the medium of primary rat hepatocytes in
      culture and the accumulation of mRNA for genes involved in carbohydrate and lipid
      metabolism was measured. Both PUFA-enriched remnants and nonesterified PUFA
      inhibited the expression and maturation of sterol response element binding
      protein-1c (SREBP-1c) and the expression of lipogenic genes regulated by this
      transcription factor. These remnants also inhibited the expression of glucose-6
      phosphate dehydrogenase (G6PD), a gene regulated at post-transcriptional steps.
      In contrast, PUFA-enriched remnants did not inhibit the accumulation of mRNA for
      malic enzyme, glucokinase, and L-pyruvate kinase, whereas nonesterified fatty
      acids caused a decrease in these mRNA. These genes are regulated independently of
      SREBP-1c. SFA-enriched remnants did not inhibit lipogenic gene expression, which
      is consistent with a lack of inhibition of lipogenesis by dietary saturated fats.
      Thus, the inhibitory action of dietary polyunsaturated fats on lipogenesis
      involves a direct action of chylomicron remnants on the liver.

PMID- 21169225
TI  - Higher branched-chain amino acid intake is associated with a lower prevalence of
      being overweight or obese in middle-aged East Asian and Western adults.
AB  - Beneficial effects on body weight of supplementation with BCAA, including
      leucine, isoleucine, and valine, have been observed in animal and human studies.
      However, population-based studies on dietary BCAA intake and body weight are
      lacking. The objective of this study was to examine the association between
      dietary BCAA intake and risk of overweight status/obesity among multi-ethnic
      populations. The International Study of Macro-/Micronutrients and Blood Pressure
      is a cross-sectional epidemiological investigation in China, Japan, the UK, and
      the US. The study cohort included 4429 men and women ages 40-59 y who were free
      of diabetes. Diet was assessed by 4 multi-pass 24-h recalls; data on nutrients
      including BCAA were derived from country-specific food tables. Overweight status
      and obesity were defined as BMI >= 25 and BMI >= 30 kg/m(2), respectively.
      Multivariable-adjusted OR of overweight status/obesity and 95% CI by quartiles of
      BCAA intake were estimated by logistic regression. Mean BCAA intake was 2.6 +/-
      0.6% energy; intake was significantly lower among Chinese participants and
      similar among participants from the other 3 countries. Compared with those in the
      first quartile, the multivariable-adjusted OR (95% CI) of overweight status from
      the 2nd to 4th quartiles of BCAA intake were 0.97 (0.80-1.17), 0.91 (0.75-1.11),
      and 0.70 (0.57-0.86), respectively (P-trend < 0.01). BCAA intake and obesity were
      also inversely associated (P-trend = 0.03). In conclusion, higher dietary BCAA
      intake is associated with lower prevalence of overweight status/obesity among
      apparently healthy middle-aged adults from East Asian and Western countries.

PMID- 21169226
TI  - Early docosahexaenoic acid supplementation of mothers during lactation leads to
      high plasma concentrations in very preterm infants.
AB  - Very preterm infants are vulnerable to deficiency in DHA. In a longitudinal
      study, 10 mothers who delivered <=29 wk gestation and planned to breast-feed
      received DHA (1200 mg/d) until 36 wk after conception. The plasma DHA status was
      assessed in their 12 infants (including 2 pairs of twins) from birth to d 49.
      Fatty acid profiles were measured weekly in breast milk, and in plasma of mothers
      and infants at baseline and at d15 and 49. Plasma and breast milk fatty acid
      concentrations in the DHA-supplemented group at d 49 were compared with a
      reference group of very preterm infants (n = 24, including triplets) whose
      mothers (n = 22) did not receive DHA during lactation. The infants' plasma DHA
      concentration tended to be greater in the DHA group than in the reference group
      (P = 0.10) and was greater when expressed as a percentage of total fatty acids (P
      = 0.009). At d 49, maternal milk DHA in the DHA group (1.92 +/- 1.10 mmol/L) was
      ~12 times higher than in the reference group (0.15 +/- 0.27 mmol/L) (P < 0.001).
      The amount of DHA provided to the infants increased from wk 1 through wk 7 in the
      DHA group (P < 0.001). Although enteral intake at wk 7 did not differ between the
      DHA group [119 +/- 51 mL/(kg.d)] and the reference group [113 +/- 66 mL/(kg.d)],
      DHA group infants received 55 +/- 38 mg/(kg.d) of DHA, and the reference group
      infants received 7 +/- 11 mg/(kg.d) (P < 0.001). Early supplementation with DHA
      to lactating mothers with low dietary DHA intake successfully increased the
      plasma DHA status in very preterm infants.

PMID- 21169227
TI  - Dietary manganese modulates expression of the manganese-containing superoxide
      dismutase gene in chickens.
AB  - To investigate the possible mechanism(s) by which dietary manganese (Mn) levels
      and sources modulate the expression of the manganese-containing superoxide
      dismutase (MnSOD) gene at both the transcriptional and translational levels, we
      used 432 8-d-old male broiler chicks in a 1 plus 4 * 2 design. Chickens were
      given either a diet without Mn supplementation [control (C)] or diets
      supplemented with 100 (optimal) or 200 (high) mg Mn/kg diet from inorganic Mn
      sulfate (I) or 3 organic complexes of Mn and amino acids with weak (W), moderate
      (M), or strong (S) chelation strength up to 21 d of age. Compared with C chicks,
      chicks fed Mn-supplemented diets had higher (P < 0.01) Mn concentrations,
      specificity protein 1 (Sp1) DNA-binding activities, MnSOD mRNA levels, MnSOD mRNA
      binding protein (MnSOD-BP) RNA-binding activities, MnSOD protein concentrations,
      and MnSOD activities within heart tissue, but lower (P < 0.01) heart activating
      protein-2 (AP-2) DNA-binding activities. Chicks fed M diets had higher (P < 0.05)
      heart Mn concentrations, MnSOD mRNA levels, and MnSOD-BP RNA-binding activities
      compared with those fed the I and W diets and lower (P < 0.01) AP-2 DNA-binding
      activities than those fed other treatment diets. These results suggest that
      dietary Mn could modulate the expression of the MnSOD gene in broilers by
      altering Sp1 and AP-2 DNA-binding activities at the transcriptional level and
      enhancing MnSOD-BP RNA-binding activity at the translational level. Additionally,
      an organic Mn source with moderate chelation strength could be more effective
      than other Mn sources in activating MnSOD gene expression at both the
      transcriptional and translational levels.

PMID- 21169228
TI  - Reduction of dietary energy density reduces body mass regain following energy
      restriction in female mice.
AB  - Restriction of energy intake induces a loss of body mass that is often regained
      when the restriction ends. We aimed to determine whether dietary energy density
      (independent of macronutrient composition) modulates postrestriction regain of
      body mass. Fifteen female mice consumed ad libitum a standard rodent diet (with
      20% added cellulose). They were then subjected to a 20% energy restriction on
      this diet for 10 d. Following restriction, mice consumed ad libitum the same diet
      with either 0 or 40% added cellulose. The study utilized a crossover design so
      all mice consumed both diets. Body temperature, physical activity, and
      digestibility were all lower when consuming the 40% cellulose diet (P < 0.001).
      Mice regained less mass (9%) when consuming the 40% than the 0% cellulose diet,
      because net energy intake was reduced by 26% (P < 0.001), despite having a
      greater gross energy intake (P < 0.001) (29%). To test whether there might be a
      constraint on intake and digestibility of the 40% cellulose diet, 20 different
      female mice consumed this diet at room temperature and were then transferred to
      the cold (7 degrees C) to determine whether they would increase intake of this
      diet in response to increased energy demands. It took up to 5 d after transfer
      for body mass, food intake, and digestibility to increase. This suggests a
      digestion constraint might have limited intake of the low-energy density diet
      immediately following restriction. Modulation of dietary energy density in the
      postrestriction phase may be a valuable strategy for maintaining mass loss
      achieved on energy-restricted diets.

PMID- 21169229
TI  - Evolution of microRNAs and the diversification of species.
AB  - MicroRNAs (miRNAs) are ancient, short noncoding RNA molecules that regulate the
      transcriptome through post-transcriptional mechanisms. miRNA riboregulation is
      involved in a diverse range of biological processes, and misregulation is
      implicated in disease. It is generally thought that miRNAs function to canalize
      cellular outputs, for instance as "fail-safe" repressors of gene misexpression.
      Genomic surveys in humans have revealed reduced genetic polymorphism and the
      signature of negative selection for both miRNAs themselves and the target
      sequences to which they are predicted to bind. We investigated the evolution of
      miRNAs and their binding sites across cichlid fishes from Lake Malawi (East
      Africa), where hundreds of diverse species have evolved in the last million
      years. Using low-coverage genome sequence data, we identified 100 cichlid miRNA
      genes with mature regions that are highly conserved in other animal species. We
      computationally predicted target sites on the 3'-untranslated regions (3'-UTRs)
      of cichlid genes to which miRNAs may bind and found that these sites possessed
      elevated single nucleotide polymorphism (SNP) densities. Furthermore, polymorphic
      sites in predicted miRNA targets showed higher minor allele frequencies on
      average and greater genetic differentiation between Malawi lineages when compared
      with a neutral expectation and nontarget 3'-UTR SNPs. Our data suggest that
      divergent selection on miRNA riboregulation may have contributed to the
      diversification of cichlid species and may similarly play a role in rapid
      phenotypic evolution of other natural systems.

PMID- 21169230
TI  - Endogenous adipocyte apolipoprotein E is colocalized with caveolin at the
      adipocyte plasma membrane.
AB  - Apolipoprotein (apo)E is well established as a secreted protein that plays an
      important role in systemic lipoprotein metabolism and vascular wall homeostasis.
      Recently, endogenous expression of apoE in adipocytes has been shown to play an
      important role in adipocyte lipoprotein metabolism and gene expression consistent
      with a nonsecreted cellular itinerary for apoE. We designed studies to evaluate
      if adipocyte apoE was retained as a constituent protein in adipocytes and to
      identify a cellular retention compartment. Using confocal microscopy,
      coimmunoprecipitation, and sucrose density cellular fractionation, we establish
      that endogenous apoE shares a cellular itinerary with the constituent protein
      caveolin-1. Altering adipocyte caveolar number by modulating cellular cholesterol
      flux or altering caveolin expression regulates the distribution of cellular apoE
      between cytoplasmic and plasma membrane compartments. A mechanism for
      colocalization of apoE with caveolin was established by demonstrating a
      noncovalent interaction between an aromatic amino acid-enriched apoE N-terminal
      domain with the caveolin scaffolding domain. Absent apoE expression in adipocytes
      alters caveolar lipid composition. These observations provide evidence for an
      interaction between two proteins involved in cellular lipid metabolism in a cell
      specialized for lipid storage and flux, and rationalize a biological basis for
      the impact of adipocyte apoE expression on adipocyte lipoprotein metabolism.

PMID- 21169231
TI  - Acupuncture for erectile dysfunction in a non-diabetic haemodialysis patient: a
      case report.
AB  - Erectile dysfunction (ED) significantly affects the quality of life in male
      haemodialysis patients. This study reports the observed effects of acupuncture
      for ED in a non-diabetic haemodialysis patient. A 43-year-old man undergoing
      haemodialysis received 12 sessions of manual acupuncture over 6 weeks and was
      observed for 6 months after the end of treatment. Total International Index of
      Erectile Function Questionnaire scores of the patient were changed from 32 at
      baseline to 60 at post-treatment evaluation, which means there was a significant
      improvement of ED. All International Index of Erectile Function subscales also
      increased. This beneficial effect lasted up to 6 months after the end of
      treatment. No adverse events were observed. An interview revealed that the
      lowered self-esteem of the patient was restored with the improvement of ED
      following acupuncture. Further controlled studies are needed to determine whether
      acupuncture might be a feasible and useful treatment option for erectile
      dysfunction in haemodialysis patients.

PMID- 21169232
TI  - Establishing an opportunistic catch up immunisation service for children
      attending an acute trust in London.

PMID- 21169234
TI  - Towards evidence based medicine for paediatricians.

PMID- 21169233
TI  - Question 1 Are oral antibiotics as efficacious as intravenous antibiotics for the
      treatment of community acquired pneumonia?

PMID- 21169235
TI  - Question 2 Should phenytoin and carbamazepine be avoided in Asian populations
      with the HLA-B*1502 positive genetic variant?

PMID- 21169236
TI  - Question 3 Ketamine or midazolam: does it matter which?

PMID- 21169237
TI  - Translational research and sport sciences.

PMID- 21169238
TI  - BJSM reviews: A-Z of nutritional supplements: dietary supplements, sports
      nutrition foods and ergogenic aids for health and performance--Part 16.

PMID- 21169239
TI  - Neuromuscular training reduces the risk of lower limb injuries.

PMID- 21169240
TI  - C-reactive protein and the newborn infant.

PMID- 21169241
TI  - Old taxa on young islands: a critique of the use of island age to date island
      endemic clades and calibrate phylogenies.

PMID- 21169242
TI  - Polo-like kinase 1 is a therapeutic target in high-risk neuroblastoma.
AB  - PURPOSE: High-risk neuroblastoma remains a therapeutic challenge for pediatric
      oncologists. The Polo-like kinase 1 (PLK1) is highly expressed in many human
      cancers and is a target of the novel small-molecule inhibitor BI 2536, which has
      shown promising anticancer activity in adult malignancies. Here, we investigated
      the effect of BI 2536 on neuroblastoma cells in vitro and in vivo to explore PLK1
      as a potential target in high-risk neuroblastoma therapy. EXPERIMENTAL DESIGN:
      PLK1 transcript levels were analyzed by microarrays in 476 primary neuroblastoma
      specimens, and correlation with prognostic markers and patient outcome was
      examined. To explore the effect of PLK1 inhibition on neuroblastoma cells, 7 cell
      lines were treated with BI 2536 and changes in growth properties were determined.
      Furthermore, nude mice with IMR-32 and SK-N-AS xenografts were treated with BI
      2536. RESULTS: PLK1 is highly expressed in unfavorable neuroblastoma and in
      neuroblastoma cell lines. Expression of PLK1 is associated with unfavorable
      prognostic markers such as stage 4, age >18 months, MYCN amplification,
      unfavorable gene expression-based classification, and adverse patient outcome (P
      < 0.001 each). On treatment with nanomolar doses of BI 2536, all neuroblastoma
      cell lines analyzed showed significantly reduced proliferation, cell cycle
      arrest, and cell death. Moreover, BI 2536 abrogated growth of neuroblastoma
      xenografts in nude mice. CONCLUSIONS: Elevated PLK1 expression is significantly
      associated with high-risk neuroblastoma and unfavorable patient outcome.
      Inhibition of PLK1 using BI 2536 exhibits strong antitumor activity on human
      neuroblastoma cells in vitro and in vivo, opening encouraging new perspectives
      for the treatment of high-risk neuroblastoma.

PMID- 21169243
TI  - CYP24A1 is an independent prognostic marker of survival in patients with lung
      adenocarcinoma.
AB  - PURPOSE: The active form of vitamin D, 1alpha,25-dihydroxyvitamin D(3) (1,25
      D(3)), exerts antiproliferative effects in cancers, including lung adenocarcinoma
      (AC). CYP24A1 is overexpressed in many cancers and encodes the enzyme that
      catabolizes 1,25-D(3). The purpose of our study was to assess CYP24A1 as a
      prognostic marker and to study its relevance to antiproliferative activity of
      1,25-D(3) in lung AC cells. EXPERIMENTAL DESIGN: Tumors and corresponding normal
      specimens from 86 patients with lung AC (stages I-III) were available. Affymetrix
      array data and subsequent confirmation by quantitative real time-PCR were used to
      determine CYP24A1 mRNA expression. A subsequent validation set of 101 lung AC was
      used to confirm CYP24A1 mRNA expression and its associations with clinical
      variables. The antiproliferative effects of 1,25-D(3) were examined using lung
      cancer cell lines with high as well as low expression of CYP24A1 mRNA. RESULTS:
      CYP24A1 mRNA was elevated 8- to 50-fold in lung AC (compared to normal
      nonneoplastic lung) and significantly higher in poorly differentiated cancers. At
      5 years of follow-up, the probability of survival was 42% (high CYP24A1, n = 29)
      versus 81% (low CYP24A1, n = 57) (P = 0.007). The validation set of 101 tumors
      showed that CYP24A1 was independently prognostic of survival (multivariate Cox
      model adjusted for age, gender, and stage, P = 0.001). A549 cells (high CYP24A1)
      were more resistant to antiproliferative effects of 1,25-D(3) compared with SKLU
      1 cells (low CYP24A1). CONCLUSIONS: CYP24A1 overexpression is associated with
      poorer survival in lung AC. This may relate to abrogation of antiproliferative
      effects of 1,25-D(3) in high CYP24A1 expressing lung AC.

PMID- 21169246
TI  - Striving to improve outcomes in oncology: unmet expectations in a complex
      disease.

PMID- 21169245
TI  - Toward a better understanding of race and cancer.
AB  - A better understanding of breast cancer subtypes is allowing their use as
      prognostic markers. For some time, it has been documented that black women with
      breast cancer have a poorer prognosis than white women of the same stage.
      Advances in immunohistochemistry and the appreciation of breast cancer subtypes
      are enabling investigators to study the distribution of these subtypes among
      populations.

PMID- 21169247
TI  - Translating clinical trials into meaningful outcomes.
AB  - Efforts to unravel the complex biology that is necessary to develop new therapies
      best suited for an individual with cancer are at a crossroads with a strained
      health care system and an insufficient clinical trial apparatus. The resulting
      failures have been described as the "valley of death." Progress into the future
      will require new considerations and the engagement of a broad band of
      stakeholders. To identify novel therapeutics that are likely to succeed in late
      development and to be meaningful for clinical practice, investigators will need
      to make a paradigm shift in designing clinical trials and endpoints while
      adhering to scientific rigor when interpreting results and making informed
      decisions. Large phase III trials that show a modest incremental benefit will
      continue to diminish in value for patients, clinicians, payers, and industry.
      Outcomes that are robust in both magnitude and application to the real world will
      take on increasing importance. Ensuring active participation by patients,
      lowering barriers to health care access, and protecting patients through health
      care reform are requirements for the future success of the cancer clinical
      research enterprise. The challenge today is to develop new approaches to
      translate scientific discovery into cost-effective and meaningful improvements in
      cancer outcomes.

PMID- 21169248
TI  - Making the investigational oncology pipeline more efficient and effective: are we
      headed in the right direction?
AB  - Advances in our knowledge of the molecular mechanisms involved in cancer biology
      have contributed to an increase in novel target-specific oncology therapeutics.
      Unfortunately, clinical development of new drugs is an expensive and slow
      process, and the patient and financial resources needed to study the vast number
      of potential therapies are limited, requiring novel approaches to clinical trial
      design and patient recruitment. In addition, traditional efficacy endpoints may
      not be adequate to fully determine the therapeutic worth of the new classes of
      targeted agents. In this new era of drug development, it has become increasingly
      clear that new clinical trial design paradigms that examine nontraditional
      endpoints have become necessary to assist in prioritizing the development of the
      most promising agents. It is also vital that individual patient management be
      considered, and the subpopulations of patients most likely to derive benefit or
      experience harm from a new therapy be identified as early as possible. Phase I
      and II clinical trials allow investigators doing clinical research the
      opportunity to define these critical endpoints and subpopulations early on,
      before conducting large-scale randomized phase III clinical trials, which require
      an abundance of financial and patient resources.

PMID- 21169249
TI  - Evaluating patient-centered outcomes in the randomized controlled trial and
      beyond: informing the future with lessons from the past.
AB  - In the era of molecular oncology, patients still define a useful therapy as one
      that allows them to live longer and helps them to live better. Although patient
      outcomes have clearly improved as a result of randomized controlled trials (RCT),
      it is critical that contemporary trials retain the perspective of these
      fundamental patient-centered outcomes. Trends in study design, results, and
      interpretation of oncology RCTs from the past provide a useful framework in which
      to consider how the research community may approach trial design in the future.
      Although the RCT remains the standard for establishing efficacy, this article
      also considers how population-based outcome studies can provide insight into
      effectiveness of new therapies and explores how the results of RCTs translate
      into benefit in the general population.

PMID- 21169250
TI  - Biologically targeted cancer therapy and marginal benefits: are we making too
      much of too little or are we achieving too little by giving too much?
AB  - We describe the development and approval of biologically targeted agents in the
      clinic through examples chosen from the experience with inhibitors of the
      epidermal growth factor (EGF) and VEGF pathways. Despite extensive biological
      rationale for the use of these classes of molecules, marginal clinical benefits
      have been observed in broad patient populations, and the agents have entered into
      general clinical practice. We discuss why this situation is unsatisfactory
      because marginal general benefit may often be at the expense of toxicity to
      nonbenefiting or even harmed patients. Finally, we point out that emerging
      technologies bring the promise of allowing the identification of patients who
      might potentially benefit from a therapy. However, development of this technology
      will not move forward without broader recognition of its need by the range of
      stakeholders, including patients, advocates, academic and private oncologists,
      drug sponsors, and those who develop drugs and diagnostic tests.

PMID- 21169251
TI  - Explaining marginal benefits to patients, when "marginal" means additional but
      not necessarily small.
AB  - Patients and their families want us to be realistic, honest, and caring about
      their prognosis and their options, even when the news is bad. Most oncologists
      will tell a patient if he is not curable, but not give specific survival
      information unless prompted. As an example, chemotherapy for pancreas cancer
      improves survival and does not worsen quality of life, but the impact on lifespan
      is small. Patients with advanced pancreas cancer have options that increase their
      average survival by about 16/100 at 1 year, and by about 9 weeks compared with
      best supportive care, but almost all patients are dead by 24 months. As an
      example of "marginal benefit" ("marginal" is defined here as more than that
      offered by the alternative care, not necessarily small or worthless), erlotinib
      added to gemcitabine compared with gemcitabine alone improves survival by six
      additional people at 1 year, and an average of 2 weeks, with no survival tail. In
      addition, the additional drug cost alone can be more than $12,000 a month. We use
      this clinical practice as a way to describe marginal benefit to patients. Telling
      patients that they have incurable disease and that treatment is ineffective is
      hard. Partly as a result, only about a third of cancer patients are told they are
      going to die, and those who are not told live no longer but have worse medical
      outcomes, such as dying on a ventilator and less time with hospice. These
      difficult conversations can be done if the oncologist has the right medical
      information, the right script, and some decision aids.

PMID- 21169252
TI  - The 2010 Health Care Reform Act: a potential opportunity to advance cancer
      research by taking cancer personally.
AB  - The Patient Protection and Affordable Care Act of 2010 will have a profound
      influence on health care in the United States, including how we conduct cancer
      research and cancer care delivery. For this reason, oncologists and researchers
      must be intimately involved in the implementation and interpretation of this
      important legislation. A major goal of the Act is to improve access to
      affordable, quality health care. An important element in achieving this goal will
      be to learn from patients' experiences and build the foundation for evidence
      based personalized medicine. This will require a partnership among researchers,
      clinicians, policy makers and regulators, and patients to design an integrated
      information network system that will be the basis for providing the right
      treatment for the right patient in the right place at the right time. In this
      review, we will discuss the salient points of the Act that specifically affect
      cancer research and care, as well as highlight opportunities for oncologists and
      researchers to play a primary role in developing a health care system that
      includes personalized medicine approaches that will in turn enhance the
      likelihood of achieving the goals and objectives of the health care reform act.

PMID- 21169253
TI  - The impact of insurance on access to cancer clinical trials at a comprehensive
      cancer center.
AB  - PURPOSE: Cancer patients at Johns Hopkins undergo insurance clearance to verify
      coverage for enrollment to interventional clinical trials. We sought to explore
      the impact of insurance clearance on disparities in access to cancer clinical
      trials at this urban comprehensive cancer center. EXPERIMENTAL DESIGN: We
      evaluated the frequency of insurance-based denial of access to cancer clinical
      trials over a 5-year period after initiation of a formal insurance clearance
      process. We used a case-control design to compare demographic and clinical
      parameters of patients denied or approved for clinical trials participation by
      their insurance company in a 3-year interval. RESULTS: From July 2003 to July
      2008, insurance requests for clinical trial participation were submitted on 4,617
      consented cancer patients at Johns Hopkins. A total of 628 patients (13.6%) with
      health insurance were denied therapeutic trial enrollment owing to lack of
      insurance coverage for participation. A total of 254 patients denied enrollment
      from 2005 to 2007 were selected for further analysis. Two-hundred sixty randomly
      selected patients approved for clinical trial participation served as controls.
      Patients approved were on average older (59.2 versus 54.9 years) than patients
      denied (P = 0.0001). Residents of Pennsylvania, which lacks a state law mandating
      cancer clinical trial coverage for residents, were overrepresented among the
      denied patients (P = 0.0009). No statistically significant variance in the
      likelihood of insurance denial was found on the basis of sex, race, stage of
      disease, or presence of comorbidities. CONCLUSIONS: Denial of access to
      therapeutic clinical trials, even among insured patients, is a significant
      barrier to clinical cancer research. This barrier spans racial, ethnic, and
      gender categories.

PMID- 21169254
TI  - Value and cancer care: toward an equitable future.
AB  - Health care expenses in the United States are increasing inexorably. At the
      current rate of growth, it is anticipated that 20% of the gross national product
      will consist of health-related expenditures within the next decade. Cancer is the
      second leading cause of death in the United States, and it is increasing in
      prevalence because of the aging of the population and the limited number of
      successful prevention strategies. As the biological characteristics of cancer
      come into sharper focus, targeted therapies are being developed that offer the
      promise of increased clinical benefit with fewer toxicities than are associated
      with conventional treatment. Although spectacular successes are infrequent with
      this approach, to date, the majority of targeted therapies are modestly effective
      at best, and extremely costly. This observation suggests that a broadly
      acceptable definition of value in a cancer therapeutic agent is not at hand, but
      is sorely needed from the vantage points of the patient and society. A corollary
      issue of enormous import is how to equitably distribute the health care dollar in
      the service of achieving the greatest good for the greatest number. Although
      cancer is responsible for only 5% of the health care budget, its cost is
      increasing and it can be viewed as paradigmatic when contemplating the problem of
      equity in health care. Here, a number of concepts are discussed that focus on
      this goal and its implications for the cancer patient and society at large.

PMID- 21169255
TI  - Vertical targeting of the phosphatidylinositol-3 kinase pathway as a strategy for
      treating melanoma.
AB  - PURPOSE: Melanoma is relatively resistant to chemotherapy; improved targeting of
      molecules critical for cell proliferation and survival are needed.
      Phosphatidylinositol-3 kinase (PI3K) is an important target in melanoma; however,
      activity of PI3K inhibitors (PI3KI) is limited. Our purpose was to assess mTOR as
      a cotarget for PI3K. METHODS: Using a method of quantitative immunofluorescence
      to measure mTOR expression in a large melanoma cohort, we studied associations
      with PI3K subunits, p85 and p110alpha. We assessed addition of the mTOR inhibitor
      rapamycin to 2 PI3KIs, NVP-BKM120 and LY294002. We studied in vitro activity of a
      novel dual PI3K/mTOR inhibitor NVP-BEZ235 and activity of the combination of NVP
      BEZ235 and the MAP/ERK kinase (MEK) inhibitor AZD6244. RESULTS: Strong
      coexpression of mTOR and p110alpha was observed (rho = 0.658; P < 0.0001). Less
      coexpression was seen with p85 (rho = 0.239; P < 0.0001). Strong synergism was
      shown between rapamycin and both PI3KIs. Activity of both PI3KIs was similarly
      enhanced with all rapamycin concentrations used. The dual PI3K/mTOR inhibitor
      effectively inhibited viability in 23 melanoma cell lines (IC(50) values in the
      nanomolar range), regardless of B-Raf mutation status, with resultant reduction
      in clonogenicity and downregulation of pAkt and pP70S6K. Synergism was seen when
      combining NVP-BEZ235 and AZD6244, with resultant increases in poly(ADP-ribose)
      polymerase and caspase-2 cleavage. CONCLUSIONS: mTOR and p110alpha are
      coexpressed in melanoma. Rapamycin concentrations as low as 1 nmol/L enhance
      activity of PI3KIs. The dual PI3K/mTOR inhibitor NVP-BEZ235 is highly active in
      melanoma cells in vitro, suggesting that concurrent PI3K and mTOR targeting in
      melanoma warrants further investigation, both alone and in combination with MEK
      inhibitors.

PMID- 21169256
TI  - The oncogenic BRAF kinase inhibitor PLX4032/RG7204 does not affect the viability
      or function of human lymphocytes across a wide range of concentrations.
AB  - PURPOSE: PLX4032 (RG7204), an oncogenic BRAF kinase inhibitor undergoing clinical
      evaluation, has high response rates in early clinical trials in patients with
      advanced BRAF(V600E) mutant melanoma. Combining PLX4032 with immunotherapy may
      allow expanding the durability of responses. The effects of PLX4032 on immune
      cells were studied to explore the feasibility of future combinatorial approaches
      with immunotherapy for melanoma. EXPERIMENTAL DESIGN: Peripheral blood
      mononuclear cells (PBMC) and BRAF(V600E) mutant melanoma cells were exposed to
      increasing concentrations of PLX4032 and the cell viability, proliferation, cell
      cycle, apoptosis, and phosphorylation of signaling proteins were analyzed.
      Effects of PLX4032 on antigen-specific T-cell function were analyzed by specific
      cytokine release and cytotoxicity activity. RESULTS: The 50% inhibition
      concentration (IC(50)) of PLX4032 for resting human PBMC was between 50 and 150
      MUmol/L compared with an IC(50) below 1 MUmol/L for sensitive BRAF(V600E) mutant
      melanoma cell lines. Activated lymphocytes were even more resistant with no
      growth inhibition up to concentrations of 250 MUmol/L. PLX4032 had a marginal
      effect on cell-cycle arrest, apoptotic cell changes or alteration of
      phosphorylated signaling molecules in lymphocytes. Functional analysis of
      specific antigen recognition showed preserved T-cell function up to 10-MUmol/L
      concentration of PLX4032, whereas the cytotoxic activity of PLX4032 was
      maintained up to high concentrations of 50 MUmol/L. CONCLUSIONS: The preserved
      viability and function of lymphocytes exposed to high concentrations of PLX4032
      suggest that this agent could be a potential candidate for combining with
      immunotherapy strategies for the treatment of patients with BRAF(V600)(E) mutant
      melanoma.

PMID- 21169257
TI  - The Notch target Hes1 directly modulates Gli1 expression and Hedgehog signaling:
      a potential mechanism of therapeutic resistance.
AB  - PURPOSE: Multiple developmental pathways including Notch, Hedgehog, and Wnt are
      active in malignant brain tumors such as medulloblastoma and glioblastoma (GBM).
      This raises the possibility that tumors might compensate for therapy directed
      against one pathway by upregulating a different one. We investigated whether
      brain tumors show resistance to therapies against Notch, and whether targeting
      multiple pathways simultaneously would kill brain tumor cells more effectively
      than monotherapy. EXPERIMENTAL DESIGN: We used GBM neurosphere lines to
      investigate the effects of a gamma-secretase inhibitor (MRK-003) on tumor growth,
      and chromatin immunoprecipitation to study the regulation of other genes by Notch
      targets. We also evaluated the effect of combined therapy with a Hedgehog
      inhibitor (cyclopamine) in GBM and medulloblastoma lines, and in primary human
      GBM cultures. RESULTS: GBM cells are at least partially resistant to long-term
      MRK-003 treatment, despite ongoing Notch pathway suppression, and show
      concomitant upregulation of Wnt and Hedgehog activity. The Notch target Hes1, a
      repressive transcription factor, bound the Gli1 first intron, and may inhibit its
      expression. Similar results were observed in a melanoma-derived cell line.
      Targeting Notch and Hedgehog simultaneously induced apoptosis, decreased cell
      growth, and inhibited colony-forming ability more dramatically than monotherapy.
      Low-passage neurospheres isolated from freshly resected human GBMs were also
      highly susceptible to coinhibition of the two pathways, indicating that targeting
      multiple developmental pathways can be more effective than monotherapy at
      eliminating GBM-derived cells. CONCLUSIONS: Notch may directly suppress Hedgehog
      via Hes1 mediated inhibition of Gli1 transcription, and targeting both pathways
      simultaneously may be more effective at eliminating GBMs cells.

PMID- 21169258
TI  - A hypoxia- and {alpha}-fetoprotein-dependent oncolytic adenovirus exhibits
      specific killing of hepatocellular carcinomas.
AB  - PURPOSE: Oncolytic adenoviruses (Ad) constitute a new promising modality of
      cancer gene therapy that displays improved efficacy over nonreplicating Ads. We
      have previously shown that an E1B 19-kDa-deleted oncolytic Ad exhibits a strong
      cell-killing effect but lacks tumor selectivity. To achieve hepatoma-restricted
      cytotoxicity and enhance replication of Ad within the context of tumor
      microenvironment, we used a modified human alpha-fetoprotein (hAFP) promoter to
      control the replication of Ad with a hypoxia response element (HRE). EXPERIMENTAL
      DESIGN: We constructed Ad-HRE(6)/hAFPDelta19 and Ad-HRE(12)/hAFPDelta19 that
      incorporated either 6 or 12 copies of HRE upstream of promoter. The promoter
      activity and specificity to hepatoma were examined by luciferase assay and
      fluorescence-activated cell sorting analysis. In addition, the AFP expression-
      and hypoxia-dependent in vitro cytotoxicity of Ad-HRE(6)/hAFPDelta19 and Ad
      HRE(12)/hAFPDelta19 was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay and cytopathic effect assay. In vivo
      tumoricidal activity on subcutaneous and liver orthotopic model was monitored by
      noninvasive molecular imaging. RESULTS: Ad-HRE(12)/hAFPDelta19 exhibited enhanced
      tumor selectivity and cell-killing activity when compared with Ad-hAFPDelta19.
      The tumoricidal activity of Ad-HRE(12)/hAFPDelta19 resulted in significant
      inhibition of tumor growth in both subcutaneous and orthotopic models. Histologic
      examination of the primary tumor after treatment confirmed accumulation of viral
      particles near hypoxic areas. Furthermore, Ad-HRE(12)/hAFPDelta19 did not cause
      severe inflammatory immune response and toxicity after systemic injection.
      CONCLUSIONS: The results presented here show the advantages of incorporating HREs
      into a hAFP promoter-driven oncolytic virus. This system is unique in that it
      acts in both a tissue-specific and tumor environment-selective manner. The
      greatly enhanced selectivity and tumoricidal activity of Ad-HRE(12)/hAFPDelta19
      make it a promising therapeutic agent in the treatment of liver cancers.

PMID- 21169259
TI  - Intrinsic breast tumor subtypes, race, and long-term survival in the Carolina
      Breast Cancer Study.
AB  - PURPOSE: Previous research identified differences in breast cancer-specific
      mortality across 4 intrinsic tumor subtypes: luminal A, luminal B, basal-like,
      and human epidermal growth factor receptor 2 positive/estrogen receptor negative
      (HER2(+)/ER(-)). EXPERIMENTAL DESIGN: We used immunohistochemical markers to
      subtype 1,149 invasive breast cancer patients (518 African American, 631 white)
      in the Carolina Breast Cancer Study, a population-based study of women diagnosed
      with breast cancer. Vital status was determined through 2006 using the National
      Death Index, with median follow-up of 9 years. RESULTS: Cancer subtypes luminal
      A, luminal B, basal-like, and HER2(+)/ER(-) were distributed as 64%, 11%, 11%,
      and 5% for whites, and 48%, 8%, 22%, and 7% for African Americans, respectively.
      Breast cancer mortality was higher for participants with HER2(+)/ER(-) and basal
      like breast cancer compared with luminal A and B. African Americans had higher
      breast cancer-specific mortality than whites, but the effect of race was
      statistically significant only among women with luminal A breast cancer. However,
      when compared with the luminal A subtype within racial categories, mortality for
      participants with basal-like breast cancer was higher among whites (HR = 2.0, 95%
      CI: 1.2-3.4) than African Americans (HR = 1.5, 95% CI: 1.0-2.4), with the
      strongest effect seen in postmenopausal white women (HR = 3.9, 95% CI: 1.5-10.0).
      CONCLUSIONS: Our results confirm the association of basal-like breast cancer with
      poor prognosis and suggest that basal-like breast cancer is not an inherently
      more aggressive disease in African American women compared with whites.
      Additional analyses are needed in populations with known treatment profiles to
      understand the role of tumor subtypes and race in breast cancer mortality, and in
      particular our finding that among women with luminal A breast cancer, African
      Americans have higher mortality than whites.

PMID- 21169261
TI  - Chromosome 17 polysomy without HER2 amplification does not predict response to
      lapatinib in metastatic breast cancer--letter.

PMID- 21169263
TI  - Do rectal cancer patients with PIK3CA mutations benefit from preoperative
      radiotherapy with regard to local recurrences?

PMID- 21169264
TI  - Clinical usefulness of microarrays for cancer prognosis in 2010--letter.

PMID- 21169267
TI  - Familial pattern of Salzmann-type nodular corneal degeneration - a four
      generation series. Reply to Papanikolaou et al.

PMID- 21169268
TI  - Long-term outcomes of laser iridotomy in Vietnamese patients with primary angle
      closure.
AB  - BACKGROUND/AIMS: To investigate the long-term outcomes of laser peripheral
      iridotomy (LPI) on controlling intraocular pressure (IOP) and progression of
      angle closure in Vietnamese. METHODS: Medical charts of Vietnamese patients who
      were diagnosed as having primary angle-closure suspect (PACS), primary angle
      closure (PAC) or primary angle-closure glaucoma (PACG), and who had received LPI
      at least 10 years prior, in a single private practice were reviewed. The main
      outcomes included use of further treatments after LPI, progression rate to
      another classification category and ocular characteristics associated with
      progression. RESULTS: 359 patients with a mean follow-up period of 11.8 +/- 1.6
      years after the LPI were included in this study. The proportion of patients who
      required additional therapies (medical, laser or surgical) to control IOP were
      7.1, 42.4 and 100% in the PACS, PAC and PACG groups, respectively. Fifty-three
      patients with PACS (22.2%) progressed to PAC; nine patients with PACS (3.8%)
      progressed to PACG; and five PAC patients (5.2%) progressed to PACG. Cataract
      surgery was a significant factor associated with PACS eyes without progression
      (p=0.019). CONCLUSIONS: Further medications, laser or surgery are frequently
      required to control IOP after LPI for eyes with PAC, especially for eyes with
      PACG. Lens extraction seems to play a protective role in PACS eyes. Close follow
      up after LPI remains necessary to prevent progression of disease.

PMID- 21169260
TI  - Gene polymorphisms in cyclophosphamide metabolism pathway,treatment-related
      toxicity, and disease-free survival in SWOG 8897 clinical trial for breast
      cancer.
AB  - PURPOSE: There are no established genetic markers for prediction of outcomes
      after cyclophosphamide (CP)-containing adjuvant therapy for breast cancer. In an
      ancillary study to a SWOG (Southwest Oncology Group) trial (S8897), we
      investigated functional polymorphisms in 4 genes in CP pharmacokinetic pathways
      in relation to hematologic toxicity and disease-free survival (DFS). EXPERIMENTAL
      DESIGN: Germline DNA was available from 458 women who were at high risk of
      relapse and was randomized to CAF (CP, intravenous doxorubicin, and 5
      fluorouracil) versus CMF (CP, intravenous methotrexate, and 5-fluorouracil) +/-
      tamoxifen, and from 874 women who had a presumed favorable prognosis and did not
      receive adjuvant therapy. Odds ratios for grade 3 and 4 hematologic toxicity in
      the treated group and hazard ratios for DFS associated with selected functional
      polymorphisms in CYP2B6CYP3A4GSTA1 and GSTP1 were estimated by logistic
      regression and Cox proportional hazard regression. RESULTS: Compared with women
      with AA genotypes, those with at least 1 GSTP1 variant G allele had reduced risk
      of grade 3 and 4 neutropenia [odds ratios (OR) = 0.63, 95% CI = 0.41-0.97] and
      leucopenia (OR = 0.59, 95% CI = 0.39-0.89). No other associations between single
      nucleotide polymorphisms and toxicity or survival were found in the treated or
      untreated group. CONCLUSION: Known genetic variants in genes involved in CP
      pharmacokinetics may not have major effects on DFS in breast cancer patients. The
      lower risk of developing high-grade hematologic toxicity among women with variant
      GSTP1 alleles suggests that genetic markers in combination with clinical factors
      may be useful in defining a subgroup of women who are less susceptible to adverse
      hematologic toxicities with CP-containing therapies.

PMID- 21169269
TI  - Outcome of trabeculectomy with mitomycin C in patients with advanced glaucoma.
AB  - BACKGROUND/AIMS: To determine the medium-term intraocular pressure (IOP) control
      and visual outcomes for patients with advanced glaucoma undergoing trabeculectomy
      with mitomycin C. METHODS: All patients with advanced glaucoma (MD -20 dB or
      above) undergoing trabeculectomy with mitomycin C between 2000 and 2008 under the
      care of a single glaucoma surgeon were included. IOP, visual acuity and visual
      field outcomes were assessed from data prospectively collected into a surgical
      outcome database. RESULTS: 103 patients were eligible for inclusion. The post
      trabeculectomy group mean IOP varied between 11.3 and 13.3 mm Hg between 1 and 7
      years. At year 5, 85.2% had an IOP of <16 mm Hg, and 96.3% had an IOP of < 21 mm
      Hg. The number completing a reliable visual-field exam decreased significantly
      year on year, but the change in mean MD for the group as a whole and for
      individual patients remained stable. 28 patients experienced a significant
      reduction in acuity defined as two or more lines of Snellen, although this was
      not due to glaucoma surgery in the majority. The only preoperative determinant
      for a significant reduction in VA was the preoperative MD (-27.00 dB (n=21)
      compared with -24.79 dB (n=63; p=0.029)). CONCLUSION: Trabeculectomy is a
      successsful method of controlling IOP in the short to medium term in patients
      with advanced glaucoma.

PMID- 21169270
TI  - How large should an iridotomy be?

PMID- 21169271
TI  - Donor tissue preparation for Descemet membrane endothelial keratoplasty.

PMID- 21169272
TI  - Predictive value of the efficacy of glaucoma medications in animal models:
      preclinical to regulatory studies.
AB  - To gain regulatory approval for a new medicine, a pharmaceutical company must
      take the new product through a series of clinical trials (Phases I-III). Animal
      models are important in the new drug-development process because they allow for
      the testing of the efficacy and safety of potential new medicines in a cost
      efficient manner that avoids the risk of serious adverse events to humans.
      Unfortunately, there is no perfect animal treatment model for glaucoma. Animal
      studies hopefully predict the results of clinical studies, but with estimating
      efficacy, the limited size and duration of these studies, as well as the animal
      model selection, might restrict the ability to accurately predict future results.
      There is little information which compares various available animal models and
      how well these preclinical studies predict the efficacy of a new product in
      clinical trials. The purpose of this review article is to analyse animal model
      studies evaluating potential glaucoma products and determine parameters
      associated with commercial availability. We discuss how animal models provide
      some success in predicting commercial launch of a new glaucoma medicine,
      especially the hypertensive and monkey models, but highlight that caution must be
      used in interpreting individual models or studies.

PMID- 21169273
TI  - The development of human organotypic retinal cultures (HORCs) to study retinal
      neurodegeneration.
AB  - AIMS: To develop human organotypic retinal cultures (HORCs) to study retinal
      ganglion cell (RGC) death in response to ischaemic and excitotoxic insults, both
      known to cause loss of RGCs and proposed as mechanisms involved in glaucomatous
      retinal neurodegeneration. METHODS: Human donor eyes were obtained within 24 h
      post mortem. The retina was isolated and explants cultured using two techniques.
      THY-1 mRNA (assessed by real-time quantitative PCR) and neuronal nuclei (NeuN)
      (assessed by immunohistochemistry) were used as markers of RGCs. Apoptosis was
      assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labelling (TUNEL). RESULTS: The distribution of THY-1 mRNA and NeuN-labelling
      within the human retina was consistent with the expected distribution of RGCs.
      Gross morphology and retinal architecture remained stable over a 96 h culture
      period. THY-1 mRNA and NeuN-labelled RGC layer cells decreased over the culture
      period, and there was an increase in TUNEL-labelling with time, but HORCs
      cultured in serum-free DMEM/HamF12 medium were useful for up to 48 h in culture.
      N-methyl-d-aspartate (10 MUM) caused a reduction in THY-1 mRNA by 24 h and
      decreased the numbers of NeuN-labelled RGC layer neurons by 48 h, suggesting that
      the loss of THY-1 mRNA was a marker of RGC stress prior to death. Simulated
      ischaemia (60 min oxygen/glucose deprivation) caused a reduction at 24 h in both
      THY-1 mRNA and the numbers of NeuN-labelled neurons of HORCs. CONCLUSION: HORCs
      provide a useful model to investigate RGC insult by neurodegenerative mechanisms
      that may lead to glaucoma in human eyes.

PMID- 21169274
TI  - Symptom validity testing and its underlying psychophysiological response pattern:
      a preliminary study.
AB  - Very little is known about the autonomic psychophysiological responses while
      individuals are executing a Symptom Validity Test. Therefore, the aim of this
      study is to analyze the peripheral psychophysiological correlates (electrodermal
      conductance and heart rate) during the performance of the Victoria Symptom
      Validity Test (VSVT). The sample of this study was composed of 30 participants
      who underwent the VSVT under two conditions: Exaggeration of cognitive deficits
      (ECD) and normal effort. Our results showed differences on skin conductance
      between correct answers and errors limited to the decision-making phase of the
      ECD condition. Those differences found in the maximum conductance value when
      participants decide to simulate their deficits could be related to emotional
      activation. No differences were found on the variable heart rate between the two
      conditions of the study. Implications of these results are discussed.

PMID- 21169275
TI  - CpG island methylator phenotype of cell-cycle regulators associated with TNM
      stage and poor prognosis in patients with oesophageal squamous cell carcinoma.
AB  - AIMS: CpG island methylator phenotype (CIMP) involves the targeting of multiple
      genes by promoter hypermethylation, and the cell-cycle regulatory proteins often
      change in human neoplasms. To gain insight into the role of epigenetic aberration
      of cell-cycle regulator genes in oesophagus squamous cell carcinoma (ESCC), the
      authors determined the hypermethylation profile in ESCC. METHODS: The promoter
      methylation status of nine cell-cycle regulator genes was examined in 50 ESCC, 50
      dysplastic tissues and 50 normal epithelial tissues by methylation-specific PCR.
      RESULTS: The frequency of promoter methylation was 52% for p14, 44% for p15, 50%
      for p16, 56% for p21, 38% for p27, 8% for p53, 42% for p57, 36% for p73, and 44%
      for RB1 of 50 ESCC. CIMP+ was detected in 54% (27/50) of ESCC and 8% (4/50) of
      dysplastic tissues; no CIMP+ was present in normal epithelial tissues (p<0.001).
      The results show that promoter methylation of p14, p15, p16, p21, p27, p57 and
      p73 was far more common in ESCC samples with CIMP+ than those with CIMP-. A
      significant difference between CIMP status and TNM stage and metastasis was found
      in ESCC (p<0.05). Patients with ESCC with CIMP+ had poorer 4-year survival than
      those with CIMP-. CONCLUSIONS: The results suggest that CIMP of a subset of cell
      cycle regulatory genes has an important role in the pathogenesis and progression
      of ESCC.

PMID- 21169276
TI  - Preliminary study on the correlation between grading and histology of solitary
      pulmonary nodules and contrast enhancement and [18F]fluorodeoxyglucose
      standardised uptake value after evaluation by dynamic multiphase CT and PET/CT.
AB  - AIM: To evaluate whether the histology and grading of solitary pulmonary nodules
      (SPNs) correlated with the results of dynamic multiphase multidetector CT (MDCT)
      and the [(18)F]fluorodeoxyglucose standardised uptake value (SUV) in 30 patients.
      METHODS: Chest x-rays of 270 patients with incidentally detected SPNs were
      retrospectively evaluated. Thirty patients with histologically proven SPNs were
      enrolled. On MDCT and positron emission tomography (PET)/CT images, two experts
      measured the density of nodules in all perfusion phases and the SUV. Net
      enhancement (NE) was calculated by subtracting peak pre-contrast density from
      peak post-contrast density. The Pearson test was used to correlate nodule NE,
      SUV, grading, histology and diameter. RESULTS: Of the 30 malignant SPNs, six were
      classified as G1 (median NE, 31.5 Hounsfield units (HU); median SUV, 4.8 units),
      15 were classified as G2 (median NE, 49 HU; median SUV, 6 units), and nine were
      classified as G3 (median NE, 32 HU; median SUV, 4.5 units). A highly negative
      correlation was found in G3 SPNs between NE and the corresponding diameters (r=
      0.834; p=0.00524). NE increased with the increase in diameter (r=0.982; p=0.284).
      SUV increased as the SPN diameter increased (r=0.789; p=0.421). NE and SUV were
      higher in G2 than G1 SPNs, and lower in G2 than G3 SPNs (r=0.97; p=0.137).
      CONCLUSIONS: The significant correlation in dedifferentiated (G3) SPNs between NE
      and diameter (r=-0.834; p=0.00524) supports the theory that stroma and
      neoangiogenesis are fundamental in SPN growth. The highly negative correlation
      between NE and diameter demonstrates a net decrease in perfusion despite an
      increase in dimension. The multidisciplinary approach used herein may result in a
      more precise prognosis and consequently a better therapeutic outcome,
      particularly in patients with undifferentiated lung cancer.

PMID- 21169278
TI  - Cortical cysts with hydrocephalus and ventriculitis: an unusual presentation of
      congenital toxoplasmosis at autopsy.

PMID- 21169277
TI  - MLH1 function is context dependent in colorectal cancers.
AB  - BACKGROUND AND AIMS: Loss of mismatch repair (MMR) function in sporadic
      colorectal cancer occurs most commonly because of inactivation of MLH1, and it
      causes an increase in mutation rate. However, it is uncertain whether loss of MMR
      alters any other cellular function. The aim of this study was to investigate the
      role of MMR in regulating cell numbers and apoptosis. METHODS: MLH1 protein
      levels were manipulated by (a) cloning and forcibly expressing MLH1 in HCT116 (a
      cell line with MLH1 mutation) and RKO (a cell line with MLH1 silencing), and (b)
      knockdown of MLH1 in SW480 (a cell line with normal MMR function). Cell number
      and apoptotic bodies were measured in standard and 'high stress' (ie, after
      staurosporine exposure) conditions. RESULTS: Restoration of MLH1 function in
      HCT116 and RKO resulted in increased cell number (p<0.001 for both cell lines)
      and decreased numbers of floating apoptotic bodies (p<0.01 in HCT116) in standard
      culture conditions. However, on induction of apoptotic stress, restoration of
      MLH1 resulted in reduced cell numbers (p<0.005). Knockdown of MLH1 in SW480 had
      no effect on cell numbers or apoptosis. CONCLUSIONS: MLH1 function may be context
      dependent: in 'low stress' conditions it may act to inhibit apoptosis, while in
      'high stress' conditions it may induce apoptosis. However, within the context of
      chromosomal instability, the effect of MLH1 on cell numbers is limited.

PMID- 21169279
TI  - Central venous catheter-related bacteraemia due to Microbacterium paraoxydans in
      a patient with no significant immunodeficiency.

PMID- 21169280
TI  - Under-reporting of delirium in the NHS.

PMID- 21169281
TI  - To kill two birds with one stone: a pleurocentesis that also drained pericardial
      tamponade in a stubbed patient.

PMID- 21169282
TI  - Flow-mediated constriction: further insight into a new measure of vascular
      function.

PMID- 21169283
TI  - Saphenous vein graft aneurysm connected to lung parenchyma: a very unusual cause
      of haemoptysis.

PMID- 21169284
TI  - Occurrence of left-sided heart valve involvement before right-sided heart valve
      involvement in carcinoid heart disease.
AB  - Carcinoids are rare neuroendocrine tumours that occur primarily in the
      gastrointestinal tract. Carcinoid heart disease is characterized by fibrous
      plaque deposition on the endocardial surface of the cardiac valves and chambers.
      It affects the right heart valves in 85% of cases and the left heart valves in
      15%. We present an unusual case of a patient with metastatic carcinoid heart
      disease in whom typical carcinoid aortic and mitral valve lesions developed 2
      years prior to the development of severe right-sided carcinoid valvular heart
      disease.

PMID- 21169285
TI  - Combined use of positron emission tomography and volume doubling time in lung
      cancer screening with low-dose CT scanning.
AB  - BACKGROUND: In lung cancer screening the ability to distinguish malignant from
      benign nodules is a key issue. This study evaluates the ability of positron
      emission tomography (PET) and volume doubling time (VDT) to discriminate between
      benign and malignant nodules. METHODS: From the Danish Lung Cancer Screening
      Trial, participants with indeterminate nodules who were referred for a 3-month
      rescan were investigated. Resected nodules and indolent nodules (ie, stable for
      at least 2 years) were included. Between the initial scan and the 3-month rescan,
      participants were referred for PET. Uptake on PET was categorised as most likely
      benign to malignant (grades I-IV). VDT was calculated from volume measurements on
      repeated CT scans using semiautomated pulmonary nodule evaluation software.
      Receiver operating characteristic (ROC) analyses were used to determine the
      sensitivity and specificity of PET and VDT. RESULTS: A total of 54 nodules were
      included. The prevalence of lung cancer was 37%. In the multivariate model both
      PET (OR 2.63, p<0.01) and VDT (OR 2.69, p<0.01) were associated with lung cancer.
      The sensitivities and specificities of both PET and VDT were 71% and 91%,
      respectively. Cut-off points for malignancy were PET>II and VDT<1 year,
      respectively. Combining PET and VDT resulted in a sensitivity of 90% and a
      specificity of 82%; ROC cut-off point was either PET or VDT indicating
      malignancy. CONCLUSION: PET and VDT predict lung cancer independently of each
      other. The use of both PET and VDT in combination is recommended when screening
      for lung cancer with low-dose CT.

PMID- 21169286
TI  - Treatment of tuberculosis and optimal dosing schedules.
AB  - Intermittent tuberculosis treatment regimens have been developed to facilitate
      treatment supervision. Their efficacy has been substantiated by clinical trials
      and tuberculosis control programmes, notwithstanding the lack of head-to-head
      comparison between daily and intermittent regimens. Recently, there has been
      opposing evidence from observational studies, pharmacokinetic-pharmacodynamic
      studies and animal models that intermittent treatment increases the risk of
      relapse, treatment failure or acquired rifamycin resistance, especially among HIV
      infected patients. Systematic reviews have been conflicting. PubMed, Ovid MEDLINE
      and EMBASE were systematically searched for publications in English to evaluate
      the evidence about dosing schedules and treatment efficacy. Levels of evidence
      and grades of recommendation were assigned largely according to clinical evidence
      with reference to the Scottish Intercollegiate Guidelines Network guideline
      development handbook. A total of 32 articles were included after excluding 331
      ineligible articles, 42 non-analytical studies, 22 narrative reviews or expert
      opinions and 44 articles embedded in systematic reviews. These included 9
      systematic reviews, 8 controlled studies, 9 pharmacokinetic-pharmacodynamic
      studies, 5 mouse studies and 1 article about guinea pig experiments. Findings
      suggest high levels of evidence for using daily dosing schedules, especially
      during the initial phase in the presence of cavitation, isoniazid resistance and
      advanced HIV co-infection, to reduce the risk of treatment failure, recurrence
      and acquired drug resistance including acquired rifamycin resistance. This review
      justifies the use of daily schedules in standard tuberculosis treatment regimens
      (particularly in the initial phase), corroborates prevailing understanding of
      pharmacokinetics-pharmacodynamics and mycobacterial persisters, and supports
      exploration of rifapentine-containing regimens in higher dosages and frequency.

PMID- 21169288
TI  - Cellular dosimetry and microdosimetry for internal electron emitters.
AB  - Radiobiological descriptions of cellular dosimetry and microdosimetry require
      both radiation dose and radiation quality. The lineal energy, defined as a ratio
      of the energy deposition by a particle in the biological target and the mean
      chord length of this target, is generally adopted to characterise the radiation
      quality. Most microdosimetry applications assume that the cell nucleus is the
      target region. Therefore, the lineal energy is obtained for the source (S) to
      target (T) geometry, T <- S, where S = cell surface, cytoplasm, cell nucleus and
      T = cell nucleus. The definition of lineal energy is based on the approximation
      that the particle mean pathlength is equal to target mean chord length. This
      approximation is valid for crossers of external irradiations. In the case of
      starters, insiders and stoppers of internal sources, particle pathlengths are
      always shorter than target chord lengths. Thus, the lineal energy does not
      reflect the specific energy deposition along particle path. In the present work,
      the specific energy deposition in a target is calculated using three distance
      parameters, i.e. target mean chord length, particle mean pathlength in the target
      and particle individual pathlength in the target. Monte Carlo calculations are
      performed for electrons of various energies and cells of different sizes. Results
      are analysed and discussed.

PMID- 21169287
TI  - Multimodality approach to mediastinal staging in non-small cell lung cancer.
      Faults and benefits of PET-CT: a randomised trial.
AB  - BACKGROUND: Correct mediastinal staging is a cornerstone in the treatment of
      patients with non-small cell lung cancer. A large range of methods is available
      for this purpose, making the process of adequate staging complex. The objective
      of this study was to describe faults and benefits of positron emission tomography
      (PET)-CT in multimodality mediastinal staging. METHODS: A randomised clinical
      trial was conducted including patients with a verified diagnosis of non-small
      cell lung cancer, who were considered operable. Patients were assigned to staging
      with PET-CT (PET-CT group) followed by invasive staging (mediastinoscopy and/or
      endoscopic ultrasound with fine needle aspiration (EUS-FNA)) or invasive staging
      without prior PET-CT (conventional work up (CWU) group). Mediastinal involvement
      (dichotomising N stage into N0-1 versus N2-3) was described according to CT, PET
      CT, mediastinoscopy, EUS-FNA and consensus (based on all available information),
      and compared with the final N stage as verified by thoracotomy or a conclusive
      invasive diagnostic procedure. RESULTS: A total of 189 patients were recruited,
      98 in the PET-CT group and 91 in the CWU group. In an intention-to-treat analysis
      the overall accuracy of the consensus N stage was not significantly higher in the
      PET-CT group than in the CWU group (90% (95% confidence interval 82% to 95%) vs
      85% (95% CI 77% to 91%)). Excluding the patients in whom PET-CT was not performed
      (n=14) the difference was significant (95% (95% CI 88% to 98%) vs 85% (95% CI 77%
      to 91%), p=0.034). This was mainly based on a higher sensitivity of the staging
      approach including PET-CT. CONCLUSION: An approach to lung cancer staging with
      PET-CT improves discrimination between N0-1 and N2-3. In those without enlarged
      lymph nodes and a PET-negative mediastinum the patient may proceed directly to
      surgery. However, enlarged lymph nodes on CT needs confirmation independent of
      PET findings and a positive finding on PET-CT needs confirmation before a
      decision on surgery is made. CLINICAL TRIAL NUMBER: NCT00867412.

PMID- 21169289
TI  - Radiation dose estimation of sand samples collected from different Egyptian
      beaches.
AB  - A high pure germanium detector-based gamma-ray spectroscopy low-background
      counting system was used to determine the levels of natural radioactivity from
      beach sand samples on the Egyptian coast along the Mediterranean and Red Seas.
      The activity concentrations of (226)Ra, (232)Th and (40)K were found to lie in
      the range of 30+/-11 to 60+/-14 Bq kg(-1) with a mean of 39+/-15 Bq kg(-1), 12+/
      3 to 30+/-14 Bq kg(-1) with a mean of 21+/-13 Bq kg(-1) and 392+/-22 to 413+/-22
      Bq kg(-1) with a mean of 402+/-23 Bq kg(-1), respectively. Radiation hazard
      indices and annual effective doses were evaluated and compared with the
      international data. The results indicate that the values obtained fall below the
      internationally accepted maximum limits and do not pose any significant radiation
      hazard to individuals in the study area. From these results, a radiological
      baseline map of Egyptian beaches can be drawn and used as reference information
      to assess any future alterations in the radioactivity of beach sands due to any
      changes in the sea sediments.

PMID- 21169290
TI  - Head calibration phantoms for actinides: measurements and simulations.
AB  - The paper deals with the physical skull phantoms Bundesinstitut fuer
      Strahlenschutz and BPAM-001, which are used in order to calibrate in vivo
      detection systems for estimation of (241)Am activity in the skeleton. Their voxel
      models were made and used in the Monte Carlo simulations. The results of the
      simulation were compared with measurements and reasonable agreement was observed.
      Several aspects such as materials and source distributions used in the models
      were discussed.

PMID- 21169291
TI  - Modelling lung cancer due to radon and smoking in WISMUT miners: preliminary
      results.
AB  - A mechanistic two-stage carcinogenesis model has been applied to model lung
      cancer mortality in the largest uranium-miner cohort available. Models with and
      without smoking action both fit the data well. As smoking information is largely
      missing from the cohort data, a method has been devised to project this
      information from a case-control study onto the cohort. Model calculations using
      256 projections show that the method works well. Preliminary results show that if
      an explicit smoking action is absent in the model, this is compensated by the
      values of the baseline parameters. This indicates that in earlier studies
      performed without smoking information, the results obtained for the radiation
      parameters are still valid. More importantly, the inclusion of smoking-related
      parameters shows that these mainly influence the later stages of lung-cancer
      development.

PMID- 21169292
TI  - Spatial and temporal profiles of cytokinin biosynthesis and accumulation in
      developing caryopses of maize.
AB  - BACKGROUND AND AIMS: Cytokinins are a major group of plant hormones and are
      associated with various developmental processes. Developing caryopses of maize
      have high levels of cytokinins, but little is known about their spatial and
      temporal distribution. The localization and quantification of cytokinins was
      investigated in maize (Zea mays) caryopsis from 0 to 28 d after pollination
      together with the expression and localization of isopentenyltransferase ZmIPT1
      involved in cytokinin biosynthesis and ZmCNGT, the gene putatively involved in N9
      glucosylation. METHODS: Biochemical, cellular and molecular approaches resolved
      the overall cytokinin profiles, and several gene expression assays were used for
      two critical genes to assess cytokinin cell-specific biosynthesis and conversion
      to the biologically inactive form. Cytokinins were immunolocalized for the first
      time in maize caryopses. KEY RESULTS: During the period 0-28 d after pollination
      (DAP): (1) large quantities of cytokinins were detected in the maternal pedicel
      region relative to the filial tissues during the early stages after
      fertilization; (2) unpollinated ovules did not accumulate cytokinins; (3) the
      maternal nucellar region showed little or no cytokinin signal; (4) the highest
      cytokinin concentrations in filial endosperm and embryo were detected at 12 DAP,
      predominantly zeatin riboside and zeatin-9-glucoside, respectively; and (5) a
      strong cytokinin immuno-signal was detected in specific cell types in the
      pedicel, endosperm and embryo. CONCLUSIONS: The cytokinins of developing maize
      caryopsis may originate from both local syntheses as well as by transport. High
      levels of fertilization-dependent cytokinins in the pedicel suggest filial
      control on metabolism in the maternal tissue; they may also trigger developmental
      programmed cell death in the pedicel.

PMID- 21169294
TI  - Group V secretory phospholipase A2 plays a pathogenic role in myocardial
      ischaemia-reperfusion injury.
AB  - AIMS: Group V secretory phospholipase A(2) (sPLA(2)-V) is highly expressed in the
      heart. This study examined (i) the role of sPLA(2)-V in myocardial ischaemia
      reperfusion (I/R) injury and (ii) the cooperative action of sPLA(2)-V and
      cytosolic PLA(2) (cPLA(2)) in myocardial I/R injury, using sPLA(2)-V knockout
      (sPLA(2)V(-/-)) mice. METHODS AND RESULTS: Myocardial I/R injury was created by 1
      h ligation of the left anterior descending coronary artery, followed by 24 h of
      reperfusion. The sPLA(2)V(-/-) mice had a 44% decrease in myocardial infarct
      size, a preservation of echocardiographic LV function (%fractional shortening: 40
      +/- 3.5 vs. 21 +/- 4.6, respectively), and lower content of leucotriene B(4)
      (LTB(4)) and thromboxane B(2) (TXB(2)) (40 and 37% lower, respectively) in the
      ischaemic myocardium after I/R compared with wild-type (WT) mice. Intraperitoneal
      administration of AACOCF3 or MAFP, inhibitors of cPLA(2) activity, decreased
      myocardial infarct size and myocardial content of LTB(4) and TXB(2) in both
      genotyped mice. The decrease in myocardial infarct size and content of LTB(4) and
      TXB(2) after cPLA(2) inhibitor administration was greater in WT mice than in
      sPLA(2)V(-/-) mice. I/R increased phosphorylation of extracellular signal-related
      kinase 1/2, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinases in
      the ischaemic myocardium in association with cPLA(2) phosphorylation. The I/R
      induced increase in the phosphorylation of p38 and cPLA(2) was less in sPLA(2)-V(
      /-) mice than in WT mice. Pretreatment with the p38 inhibitor SB202190 suppressed
      an increase in cPLA(2) phosphorylation after I/R in WT mice. CONCLUSION: sPLA(2)
      V plays an important role in the pathogenesis of myocardial I/R injury partly in
      concert with the activation of cPLA(2).

PMID- 21169293
TI  - Proliferating cell nuclear antigen (PCNA): a key factor in DNA replication and
      cell cycle regulation.
AB  - BACKGROUND: PCNA (proliferating cell nuclear antigen) has been found in the
      nuclei of yeast, plant and animal cells that undergo cell division, suggesting a
      function in cell cycle regulation and/or DNA replication. It subsequently became
      clear that PCNA also played a role in other processes involving the cell genome.
      SCOPE: This review discusses eukaryotic PCNA, with an emphasis on plant PCNA, in
      terms of the protein structure and its biochemical properties as well as gene
      structure, organization, expression and function. PCNA exerts a tripartite
      function by operating as (1) a sliding clamp during DNA synthesis, (2) a
      polymerase switch factor and (3) a recruitment factor. Most of its functions are
      mediated by its interactions with various proteins involved in DNA synthesis,
      repair and recombination as well as in regulation of the cell cycle and chromatid
      cohesion. Moreover, post-translational modifications of PCNA play a key role in
      regulation of its functions. Finally, a phylogenetic comparison of PCNA genes
      suggests that the multi-functionality observed in most species is a product of
      evolution. CONCLUSIONS: Most plant PCNAs exhibit features similar to those found
      for PCNAs of other eukaryotes. Similarities include: (1) a trimeric ring
      structure of the PCNA sliding clamp, (2) the involvement of PCNA in DNA
      replication and repair, (3) the ability to stimulate the activity of DNA
      polymerase delta and (4) the ability to interact with p21, a regulator of the
      cell cycle. However, many plant genomes seem to contain the second, probably
      functional, copy of the PCNA gene, in contrast to PCNA pseudogenes that are found
      in mammalian genomes.

PMID- 21169295
TI  - The endothelium-dependent effect of RTEF-1 in pressure overload cardiac
      hypertrophy: role of VEGF-B.
AB  - AIMS: Related transcription enhancer factor-1 (RTEF-1) has previously been
      demonstrated to play an important role in both endothelial cells and
      cardiomyocytes. However, the function of RTEF-1 in the communication between
      these two adjacent cell types has not been elucidated. METHODS AND RESULTS: We
      have found that endothelium-specific RTEF-1 transgenic mice (VE-Cad/RTEF-1)
      developed significant cardiac hypertrophy after transverse aortic constriction
      surgery, as evidenced by an increased ratio of heart weight to tibia length,
      enlarged cardiomyocyte size, thickened left ventricular wall and elevated
      expression of hypertrophic gene markers, with up-regulation of vascular
      endothelial growth factor B (VEGF-B). Additionally, VEGF-B was increased in
      endothelial cells from VE-Cad/RTEF-1 mice, as well as in endothelial cells with
      forced RTEF-1 expression (HMEC-1/RTEF-1), and coincidentally decreased when RTEF
      1 was deficient in HMEC-1. Using chromatin immunoprecipitation and luciferase
      assays, we found that RTEF-1 increased VEGF-B promoter activity through a direct
      interaction. Hypertrophy-associated genes and protein synthesis were up-regulated
      in cardiomyocytes that were incubated with conditioned medium from HMEC-1/RTEF-1
      and the endothelial cells of VE-Cad/RTEF-1 mice. This effect could be abrogated
      by treating the myocytes with VEGF-B small interfering RNA and extracellular
      signal-regulated kinase 1/2 inhibitor. CONCLUSION: Our data demonstrated that
      increased RTEF-1 in endothelial cells upregulates VEGF-B, which is able to
      stimulate hypertrophic genes in cardiomyocytes. These results suggest that the
      RTEF-1-driven increase of VEGF-B plays an important role in communication between
      the endothelium and myocardium.

PMID- 21169296
TI  - Evaluating a policing strategy intended to disrupt an illicit street-level drug
      market.
AB  - The authors examined a strategic policing initiative that was implemented in a
      high crime Nashville, Tennessee neighborhood by utilizing a mixed-methodological
      evaluation approach in order to provide (a) a descriptive process assessment of
      program fidelity; (b) an interrupted time-series analysis relying upon
      generalized linear models; (c) in-depth resident interviews. Results revealed
      that the initiative corresponded with a statistically significant reduction in
      drug and narcotics incidents as well as perceived changes in neighborhood
      disorder within the target community. There was less-clear evidence, however, of
      a significant impact on other outcomes examined. The implications that an
      intensive crime prevention strategy corresponded with a reduction in specific
      forms of neighborhood crime illustrates the complex considerations that law
      enforcement officials face when deciding to implement this type of crime
      prevention initiative.

PMID- 21169297
TI  - Incidence of community-acquired meticillin resistant Staphylococcus aureus hand
      infections in Tayside, Scotland: a guide to appropriate antimicrobial
      prescribing.
AB  - The prevalence of community-acquired meticillin resistant Staphylococcus aureus
      (ca-MRSA) as an important cause of hand infections has gained much recognition.
      The clinical impact of this is less well documented in the United Kingdom. This
      study looks at the incidence of hand infections in an urban Scottish teaching
      hospital over a 12 month period.

PMID- 21169298
TI  - Assessing angulation on digital images of radiographs of fractures of the distal
      radius: visual estimation versus computer software measurement.
AB  - We assessed the reliability of visual estimation of angles on computer images of
      radiographs, and compared their accuracy with the measurement of angles using
      computer software for ten distal radius fractures. We asked 73 clinicians to
      visually estimate the dorsal angulation on ten computerized radiographs of
      fractures of the distal radius. The reliability of these estimations was
      calculated. Their accuracy was compared to a 'gold standard' obtained by
      consensus agreement between three consultants measuring these angles using the
      software. Inter-observer reliability was calculated as ICC = 0.51 and intra
      observer reliability as r = 0.76. The visual estimations were less accurate with
      a mean percentage error of 31% (range, 7-83%). As angulation increased the
      estimation accuracy improved. Although reliability and accuracy of such
      estimation was better for clinicians with greater experience, actual measurement
      was more reliable and accurate.

PMID- 21169299
TI  - Diffuse infiltrative epithelioid sarcoma presenting as carpal tunnel syndrome.

PMID- 21169301
TI  - Severe hand injuries resulting from Samurai sword assaults: a Dublin case series.

PMID- 21169302
TI  - Flexor tenosynovitis caused by Mycobacterium arupense.

PMID- 21169303
TI  - A case of scar sarcoidosis presenting with a nodular mass infiltrating a neuroma
      in the hand.

PMID- 21169304
TI  - Intraosseous glomus tumour in the distal phalanx of the index finger.

PMID- 21169305
TI  - Lipoma causing posterior interosseous nerve palsy or superficial radial nerve
      paraesthesia.

PMID- 21169306
TI  - Rupture of the flexor digitorum profundus tendon after injections of insoluble
      steroid for a trigger finger.

PMID- 21169307
TI  - Kirschner wire stabilization of collateral ligament avulsion fractures of the
      base of the proximal phalanx.

PMID- 21169308
TI  - Palmar fracture-dislocation of the metacarpophalangeal joint of the thumb.

PMID- 21169309
TI  - The five-fingered hand anomaly might be considered as a variant of the atypical
      mirror hand.

PMID- 21169310
TI  - Acute-on-chronic carpal tunnel syndrome after correction of wrist drop using
      tendon transfers.

PMID- 21169311
TI  - Re: Lim et al. injection of botulinum toxin to the extensor carpi radialis brevis
      for tennis elbow.

PMID- 21169313
TI  - What is good practice in solid waste management?

PMID- 21169314
TI  - James Jackson Award.

PMID- 21169315
TI  - ISWA 2010 Publication Award winner.

PMID- 21169317
TI  - Re-analysis of risk for glioma in relation to mobile telephone use: comparison
      with the results of the Interphone international case-control study.

PMID- 21169318
TI  - Lifetime maternal experiences of abuse and risk of pre-natal depression in two
      demographically distinct populations in Boston.
AB  - BACKGROUND: To investigate lifetime history of interpersonal abuse and risk of
      pre-natal depression in socio-economically distinct populations in the same city.
      METHODS: We examined associations of physical and sexual abuse with the risk of
      pre-natal depression in two cohorts in the Boston area, including 2128
      participants recruited from a large urban- and suburban-managed care organization
      (Project Viva) and 1509 participants recruited primarily from urban community
      health centres (Project ACCESS). Protocols for the studies were designed in
      parallel to allow us to merge data to enhance ethnic and socio-economic diversity
      in the combined sample. In mid-pregnancy, the Personal Safety Questionnaire and
      Edinburgh Postnatal Depression Scale (EPDS) were administered in both cohorts. An
      EPDS score >= 13 indicated probable pre-natal depression. Logistic regression was
      used to estimate the odds ratio (OR) of pre-natal depression associated with
      lifetime abuse history. RESULTS: Project ACCESS participants were twice as likely
      as Project Viva participants to report symptoms consistent with pre-natal
      depression: 22% of Project ACCESS participants had EPDS scores >= 13, compared
      with 11% of Project Viva participants. Fifty-seven percent of women in ACCESS and
      46% in Viva reported lifetime physical and/or sexual abuse. In merged analysis,
      women reporting lifetime physical or sexual abuse had an OR for mid-pregnancy
      depression of 1.63 [95% confidence interval (95% CI): 1.29-2.07], adjusted for
      age and race/ethnicity. Lifetime histories of physical abuse [OR 1.48 (95% CI
      1.15-1.90)] and sexual abuse [OR 1.68 (95% CI 1.24-2.28)] were independently
      associated with pre-natal depression. When child/teen, pre-pregnancy adult and
      pregnancy life periods were considered simultaneously, abuse in childhood was
      independently associated with an OR of 1.23 (95% CI 1.00-1.59), pre-pregnancy
      adult abuse with an OR of 1.70 (95% CI 1.31-2.21) and abuse during pregnancy with
      an OR of 1.77 (95% CI 1.14-2.74). Further adjustment for childhood socio-economic
      position made no material difference, and there were no clear interactions
      between abuse and adult socio-economic position. CONCLUSIONS: Physical and sexual
      abuse histories were positively associated with pre-natal depression in two
      economically and ethnically distinct populations. Stronger associations with
      recent abuse may indicate that the association of abuse with depression wanes
      with time or may result from less accurate recall of remote events.

PMID- 21169319
TI  - Heart transplant.

PMID- 21169320
TI  - Getting better value from the NHS drug budget.

PMID- 21169321
TI  - Febrile neutropenia.

PMID- 21169322
TI  - Commentary: Achieving savings will not be straightforward.

PMID- 21169324
TI  - Kala-azar outbreak is symptomatic of humanitarian crisis facing southern Sudan.

PMID- 21169325
TI  - Ireland is told to provide legal abortions for women whose lives are at risk.

PMID- 21169326
TI  - European drug regulators publish their evaluation of rosiglitazone.

PMID- 21169327
TI  - Surgeon who refused to operate on man with swastika tattoo should not be
      disciplined, says German Medical Association.

PMID- 21169328
TI  - Measures to end child detention don't go far enough, says children's rights
      charity.

PMID- 21169331
TI  - Activation of the basolateral membrane Cl- conductance essential for electrogenic
      K+ secretion suppresses electrogenic Cl- secretion.
AB  - Adrenaline activates transient Cl(-) secretion and sustained K(+) secretion
      across isolated distal colonic mucosa of guinea-pigs. The Ca(2+)-activated Cl(-)
      channel inhibitor CaCCinh-A01 (30 MUm) significantly reduced electrogenic K(+)
      secretion, detected as short-circuit current (I(sc)). This inhibition supported
      the cell model for K(+) secretion in which basolateral membrane Cl(-) channels
      provide an exit pathway for Cl(-) entering the cell via Na(+)-K(+)-2Cl(-)
      cotransporters. CaCCinh-A01 inhibited both I(sc) and transepithelial conductance
      in a concentration-dependent manner (IC(50) = 6.3 MUm). Another Cl(-) channel
      inhibitor, GlyH-101, also reduced sustained adrenaline-activated I(sc) (IC(50) =
      9.4 MUm). Adrenaline activated whole-cell Cl(-) current in isolated intact
      colonic crypts, confirmed by ion substitution. This adrenaline-activated whole
      cell Cl(-) current was also inhibited by CaCCinh-A01 or GlyH-101. In contrast to
      K(+) secretion, CaCCinh-A01 augmented the electrogenic Cl(-) secretion activated
      by adrenaline as well as that activated by prostaglandin E(2). Synergistic Cl(-)
      secretion activated by cholinergic/prostaglandin E(2) stimulation was insensitive
      to CaCCinh-A01. Colonic expression of the Ca(2+)-activated Cl(-) channel protein
      Tmem16A was supported by RT-PCR detection of Tmem16A mRNA, by immunoblot with a
      Tmem16A antibody, and by detection of immunofluorescence in lateral membranes of
      epithelial cells. Alternative splices of Tmem16A were detected for exons that are
      involved in channel activation. Inhibition of K(+) secretion and augmentation of
      Cl(-) secretion by CaCCinh-A01 support a common colonic cell model for these two
      ion secretory processes, such that activation of basolateral membrane Cl(-)
      channels contributes to the production of electrogenic K(+) secretion and limits
      the rate of Cl(-) secretion. Maximal physiological Cl(-) secretion occurs only
      for synergistic activation mechanisms that close these basolateral membrane Cl(-)
      channels.

PMID- 21169332
TI  - Astrocyte chemoreceptors: mechanisms of H+ sensing by astrocytes in the
      retrotrapezoid nucleus and their possible contribution to respiratory drive.
AB  - Central chemoreception is the mechanism by which CO(2)/pH-sensitive neurons (i.e.
      chemoreceptors) regulate breathing, presumably in response to changes in tissue
      pH. A region of the brainstem called the retrotrapezoid nucleus (RTN) is thought
      to be an important site of chemoreception; select neurons (i.e. chemoreceptors)
      in this region sense changes in CO(2)/H(+) and send excitatory glutamatergic
      drive to respiratory centres to modulate the depth and frequency of breathing.
      Purinergic signalling may also contribute to chemoreception; for instance, it was
      shown in vivo that CO(2)/H(+) facilitates ATP release within the RTN to stimulate
      breathing, and recent evidence suggests that CO(2)/H(+)-sensitive RTN astrocytes
      are the source of this purinergic drive to breathe. In this review, we summarize
      evidence that RTN astrocytes sense changes in CO(2)/H(+), identify mechanisms
      that are likely to confer CO(2)/H(+) sensitivity to RTN astrocytes, including
      inhibition of heteromeric Kir4.1-Kir5.1 channels and activation of a depolarizing
      inward current generated by the sodium bicarbonate cotransporter, and discuss the
      extent to which astrocytes contribute to respiratory drive.

PMID- 21169333
TI  - Na(v)1.8 channelopathy in mutant mice deficient for myelin protein zero is
      detrimental to motor axons.
AB  - Myelin protein zero mutations were found to produce Charcot-Marie-Tooth disease
      phenotypes with various degrees of myelin impairment and axonal loss, ranging
      from the mild 'demyelinating' adult form to severe and early onset forms. Protein
      zero deficient homozygous mice ( ) show a severe and progressive dysmyelinating
      neuropathy from birth with compromised myelin compaction, hypomyelination and
      distal axonal degeneration. A previous study using immunofluorescence showed that
      motor nerves deficient of myelin protein zero upregulate the Na(V)1.8 voltage
      gated sodium channel isoform, which is normally present only in restricted
      populations of sensory axons. The aim of this study was to investigate the
      function of motor axons in protein zero-deficient mice with particular emphasis
      on ectopic Na(V)1.8 voltage gated sodium channel. We combined 'threshold
      tracking' excitability studies with conventional nerve conduction studies,
      behavioural studies using rotor-rod measurements, and histological measures to
      assess membrane dysfunction and its progression in protein zero deficient
      homozygous mutants as compared with age-matched wild-type controls. The
      involvement of Na(V)1.8 was investigated by pharmacologic block using the subtype
      selective Na(V)1.8 blocker A-803467 and chronically in Na(V)1.8 knock-outs. We
      found that in the context of dysmyelination, abnormal potassium ion currents and
      membrane depolarization, the ectopic Na(V)1.8 channels further impair the motor
      axon excitability in protein zero deficient homozygous mutants to an extent that
      precipitates conduction failure in severely affected axons. Our data suggest that
      a Na(V)1.8 channelopathy contributed to the poor motor function of protein zero
      deficient homozygous mutants, and that the conduction failure was associated with
      partially reversible reduction of the electrically evoked muscle response and of
      the clinical function as indicated by the partial recovery of function at rotor
      rod measurements. As a consequence of these findings of partially reversible
      dysfunction, we propose that the Na(V)1.8 voltage gated sodium channel should be
      considered as a novel therapeutic target for Charcot-Marie-Tooth disease.

PMID- 21169335
TI  - Resuscitation orders and their relevance to patients' clinical status and
      outcomes.
AB  - BACKGROUND: Documented resuscitation orders have relevance in the management of a
      pulseless, unresponsive patient. Although useful, the frequency of their
      documentation in the case notes of newly admitted medical patients is not well
      established. AIM: To investigate the frequency of early clear documentation of
      resuscitation orders in patients' admission notes. DESIGN: Retrospective audit.
      METHODS: The admission notes of 618 medical admissions to an Australian tertiary
      referral teaching hospital between January and December 2007 were reviewed to
      calculate the frequency of clear resuscitation documentation. Certain outcomes of
      each admission, such as in-hospital death, were obtained via hospital-based
      computerized records. RESULTS: Within the first 24 h of admission, discussions
      regarding resuscitation were not documented for 78% of patients. Of the 482
      patients with no documented resuscitation orders, 5 patients died during their
      index admission. Of the 136 patients with documented resuscitation orders, 24
      patients died during their index admission. As age or a measure of clinical
      debility increased, the absolute number and relative proportion of resuscitation
      discussions increased significantly (P<0.0001) and the number and proportion of
      patients deemed not for resuscitation also increased (P<0.0001). CONCLUSION:
      Those patients apparently targeted for discussion were older, more frail and
      acutely unwell. We propose widespread use of a clinical scoring system to
      identify those patients who need their resuscitation status clarified early in
      their admission prior to clinical deterioration.

PMID- 21169334
TI  - Nuclear factors involved in mitochondrial translation cause a subgroup of
      combined respiratory chain deficiency.
AB  - Mutations in several mitochondrial DNA and nuclear genes involved in
      mitochondrial protein synthesis have recently been reported in combined
      respiratory chain deficiency, indicating a generalized defect in mitochondrial
      translation. However, the number of patients with pathogenic mutations is small,
      implying that nuclear defects of mitochondrial translation are either
      underdiagnosed or intrauterine lethal. No comprehensive studies have been
      reported on large cohorts of patients with combined respiratory chain deficiency
      addressing the role of nuclear genes affecting mitochondrial protein synthesis to
      date. We investigated a cohort of 52 patients with combined respiratory chain
      deficiency without causative mitochondrial DNA mutations, rearrangements or
      depletion, to determine whether a defect in mitochondrial translation defines the
      pathomechanism of their clinical disease. We followed a combined approach of
      sequencing known nuclear genes involved in mitochondrial protein synthesis (EFG1,
      EFTu, EFTs, MRPS16, TRMU), as well as performing in vitro functional studies in
      22 patient cell lines. The majority of our patients were children (<15 years),
      with an early onset of symptoms <1 year of age (65%). The most frequent clinical
      presentation was mitochondrial encephalomyopathy (63%); however, a number of
      patients showed cardiomyopathy (33%), isolated myopathy (15%) or hepatopathy
      (13%). Genomic sequencing revealed compound heterozygous mutations in the
      mitochondrial transfer ribonucleic acid modifying factor (TRMU) in a single
      patient only, presenting with early onset, reversible liver disease. No
      pathogenic mutation was detected in any of the remaining 51 patients in the other
      genes analysed. In vivo labelling of mitochondrial polypeptides in 22 patient
      cell lines showed overall (three patients) or selective (four patients) defects
      of mitochondrial translation. Immunoblotting for mitochondrial proteins revealed
      decreased steady state levels of proteins in some patients, but normal or
      increased levels in others, indicating a possible compensatory mechanism. In
      summary, candidate gene sequencing in this group of patients has a very low
      detection rate (1/52), although in vivo labelling of mitochondrial translation in
      22 patient cell lines indicate that a nuclear defect affecting mitochondrial
      protein synthesis is responsible for about one-third of combined respiratory
      chain deficiencies (7/22). In the remaining patients, the impaired respiratory
      chain activity is most likely the consequence of several different events
      downstream of mitochondrial translation. Clinical classification of patients with
      biochemical analysis, genetic testing and, more importantly, in vivo labelling
      and immunoblotting of mitochondrial proteins show incoherent results, but a
      systematic review of these data in more patients may reveal underlying
      mechanisms, and facilitate the identification of novel factors involved in
      combined respiratory chain deficiency.

PMID- 21169336
TI  - High-throughput mapping of protein occupancy identifies functional elements
      without the restriction of a candidate factor approach.
AB  - There are a variety of in vivo and in vitro methods to determine the genome-wide
      specificity of a particular trans-acting factor. However there is an inherent
      limitation to these candidate approaches. Most biological studies focus on the
      regulation of particular genes, which are bound by numerous unknown trans-acting
      factors. Therefore, most biological inquiries would be better addressed by a
      method that maps all trans-acting factors that bind particular regions rather
      than identifying all regions bound by a particular trans-acting factor. Here, we
      present a high-throughput binding assay that returns thousands of unbiased
      measurements of complex formation on nucleic acid. We applied this method to
      identify transcriptional complexes that form on DNA regions upstream of genes
      involved in pluripotency in embryonic stem cells (ES cells) before and after
      differentiation. The raw binding scores, motif analysis and expression data are
      used to computationally reconstruct remodeling events returning the identity of
      the transcription factor(s) most likely to comprise the complex. The most
      significant remodeling event during ES cell differentiation occurred upstream of
      the REST gene, a transcriptional repressor that blocks neurogenesis. We also
      demonstrate how this method can be used to discover RNA elements and discuss
      applications of screening polymorphisms for allelic differences in binding.

PMID- 21169337
TI  - Folding of the lysine riboswitch: importance of peripheral elements for
      transcriptional regulation.
AB  - The Bacillus subtilis lysC lysine riboswitch modulates its own gene expression
      upon lysine binding through a transcription attenuation mechanism. The riboswitch
      aptamer is organized around a single five-way junction that provides the scaffold
      for two long-range tertiary interactions (loop L2-loop L3 and helix P2-loop L4)-
      all of this for the creation of a specific lysine binding site. We have
      determined that the interaction P2-L4 is particularly important for the
      organization of the ligand-binding site and for the riboswitch transcription
      attenuation control. Moreover, we have observed that a folding synergy between L2
      L3 and P2-L4 allows both interactions to fold at lower magnesium ion
      concentrations. The P2-L4 interaction is also critical for the close
      juxtaposition involving stems P1 and P5. This is facilitated by the presence of
      lysine, suggesting an active role of the ligand in the folding transition. We
      also show that a previously uncharacterized stem-loop located in the expression
      platform is highly important for the riboswitch activity. Thus, folding elements
      located in the aptamer and the expression platform both influence the lysine
      riboswitch gene regulation.

PMID- 21169338
TI  - Good governance and corruption in the health sector: lessons from the Karnataka
      experience.
AB  - Strengthening good governance and preventing corruption in health care are
      universal challenges. The Karnataka Lokayukta (KLA), a public complaints agency
      in Karnataka state (India), was created in 1986 but played a prominent role
      controlling systemic corruption only after a change of leadership in 2001 with a
      new Lokayukta (ombudsman) and Vigilance Director for Health (VDH). This case
      study of the KLA (2001-06) analysed the:Scope and level of poor governance in the
      health sector;  KLA objectives and its strategy;  Factors which affected public
      health sector governance and the operation of the KLA.  We used a participatory
      and opportunistic evaluation design, examined documents about KLA activities,
      conducted three site visits, two key informant and 44 semi-structured interviews
      and used a force field model to analyse the governance findings. The Lokayukta
      and his VDH were both proactive and economically independent with an extended
      social network, technical expertise in both jurisdiction and health care, and
      were widely perceived to be acting for the common good. They mobilized media and
      the public about governance issues which were affected by factors at the
      individual, organizational and societal levels. Their investigations revealed
      systemic corruption within the public health sector at all levels as well as in
      public/private collaborations and the political and justice systems. However,
      wider contextual issues limited their effectiveness in intervening. The departure
      of the Lokayukta, upon completing his term, was due to a lack of continued
      political support for controlling corruption. Governance in the health sector is
      affected by positive and negative forces. A key positive factor was the combined
      social, cultural and symbolic capital of the two leaders which empowered them to
      challenge corrupt behaviour and promote good governance. Although change was
      possible, it was precarious and requires continuous political support to be
      sustained.

PMID- 21169339
TI  - Adolescents of the US National Longitudinal Lesbian Family Study: the impact of
      having a known or an unknown donor on the stability of psychological adjustment.
AB  - BACKGROUND: The current study is based on the US National Longitudinal Lesbian
      Family Study (NLLFS), which was designed to document the development of the first
      generation of lesbian families with children conceived through donor
      insemination. Data were collected in five waves, first at insemination or during
      pregnancy, and subsequently when the index children were 2, 5, 10 and 17 years
      old. The study is ongoing, with a 93% retention rate to date. The purpose of the
      current investigation was to assess changes in psychological adjustment of the
      index offspring between the time that they were 10 and 17 years old (T4 and T5)
      and to examine the effects of having a known or an as-yet-unknown donor. METHODS:
      The total T5 sample consisted of 78 adolescents. The mothers in 74 families
      completed a Child Behaviour Checklist (CBCL) on their offspring at both T4 and
      T5: 26 of these offspring had been conceived through known sperm donors and 48
      through unknown donors. Changes in psychological adjustment were assessed through
      computations of stability coefficients between T4 and T5 on all CBCL subscales,
      and by means of a general linear model (GLM). RESULTS: On 10 out of 11 CBCL
      subscales, the stability coefficients were not significantly different for
      adolescents with known and unknown donors. Findings from the GLM showed that no
      main effect for donor type was found; for offspring in both donor groups thought
      problems and rule-breaking behaviour were higher and scores on social problems
      and aggressive behaviour were lower at T5 than T4. CONCLUSIONS: The development
      of psychological well-being in the offspring of lesbian mothers over a 7-year
      period from childhood through adolescence is the same for those who were
      conceived through known and unknown donors.

PMID- 21169341
TI  - Bookshelf: a simple curation system for the storage of biomolecular simulation
      data.
AB  - Molecular dynamics simulations can now routinely generate data sets of several
      hundreds of gigabytes in size. The ability to generate this data has become
      easier over recent years and the rate of data production is likely to increase
      rapidly in the near future. One major problem associated with this vast amount of
      data is how to store it in a way that it can be easily retrieved at a later date.
      The obvious answer to this problem is a database. However, a key issue in the
      development and maintenance of such a database is its sustainability, which in
      turn depends on the ease of the deposition and retrieval process. Encouraging
      users to care about meta-data is difficult and thus the success of any storage
      system will ultimately depend on how well used by end-users the system is. In
      this respect we suggest that even a minimal amount of metadata if stored in a
      sensible fashion is useful, if only at the level of individual research groups.
      We discuss here, a simple database system which we call 'Bookshelf', that uses
      python in conjunction with a mysql database to provide an extremely simple system
      for curating and keeping track of molecular simulation data. It provides a user
      friendly, scriptable solution to the common problem amongst biomolecular
      simulation laboratories; the storage, logging and subsequent retrieval of large
      numbers of simulations. Download URL: http://sbcb.bioch.ox.ac.uk/bookshelf/

PMID- 21169342
TI  - Comparison between cryptogenic organizing pneumonia and connective tissue disease
      related organizing pneumonia.
AB  - OBJECTIVE: Although the overall prognosis of CTD-related interstitial pneumonia
      is better than that of idiopathic interstitial pneumonia, the prognosis of CTD
      related organizing pneumonia (CTD-OP) was suggested to be worse than that of
      cryptogenic organizing pneumonia (COP). The aim of this study was to compare the
      clinical features and outcome of the two conditions. METHODS: A retrospective
      review of 100 patients diagnosed by lung biopsy as having organizing pneumonia
      patterns (CTD, 24; COP, 76) at three tertiary referral centres. RESULTS:
      Underlying CTDs were mostly RA, SS and PM/DM. The median follow-up period was
      43.6 months. There were no differences in initial symptoms, lung function or
      bronchoalveolar lavage fluid findings except significantly more females (83.3 vs.
      59.2%, P = 0.048) in the CTD-OP than in the COP group. Over 80% of the patients
      in both the groups improved. However, complete recovery rate was lower in CTD-OP
      (20.8%) than in COP (46.1%; P = 0.028) with a tendency towards higher recurrence
      rate in CTD-OP (40.0 vs 20.3%; P = 0.072). There was no significant difference in
      the frequency of rapid progression or overall survival between the two groups.
      CONCLUSIONS: The clinical features and prognosis of CTD-OP are similar to COP.
      However, lower complete recovery rate with a tendency towards higher recurrence
      rate in CTD-OP compared with COP suggest the need for closer follow-up in
      patients with CTD-OP.

PMID- 21169340
TI  - Expansion mechanisms and functional divergence of the glutathione s-transferase
      family in sorghum and other higher plants.
AB  - Glutathione S-transferases (GSTs) exist in various eukaryotes and function in
      detoxification of xenobiotics and in response to abiotic and biotic stresses. We
      have carried out a genome-wide survey of this gene family in 10 plant genomes.
      Our data show that tandem duplication has been regarded as the major expansion
      mechanism and both monocot and dicot plants may have practiced different
      expansion and evolutionary history. Non-synonymous substitutions per site (Ka)
      and synonymous substitutions per site (Ks) analyses showed that N- and C-terminal
      functional domains of GSTs (GST_N and GST_C) seem to have evolved under a strong
      purifying selection (Ka/Ks < 1) under different selective pressures. Differential
      evolutionary rates between GST_N and GST_C and high degree of expression
      divergence have been regarded as the major drivers for the retention of
      duplicated genes and the adaptability to various stresses. Expression profiling
      also indicated that the gene family plays a role not only in stress-related
      biological processes but also in the sugar-signalling pathway. Our survey
      provides additional annotation of the plant GST gene family and advance the
      understanding of plant GSTs in lineage-specific expansion and species
      diversification.

PMID- 21169343
TI  - Outcome in rheumatoid arthritis patients with continued conventional therapy for
      moderate disease activity--the early RA network (ERAN).
AB  - OBJECTIVE: To report from early RA network (ERAN) on Years 2 and 3 28-joint DAS
      (DAS-28) and HAQ outcomes in newly diagnosed RA patients treated with DMARD
      therapies stratified to DAS-28 status after 1 year. METHODS: ERAN is a
      prospective observational cohort of newly diagnosed RA patients, monitored and
      treated according to local practice. Standardized case report forms are completed
      at first presentation, 3-6 months, 1 year and annually thereafter. RESULTS: A
      total of 418 newly diagnosed RA patients with 2 years and 302 with 3 years follow
      up were identified in 22 ERAN centres from 2002 to 2008. Within their first year
      from registration, 67% of patients received monotherapy DMARDs, and 26%
      combination DMARDs including 2% were on anti-TNF therapies. Between Years 1 and
      3, 60% received DMARD monotherapy, 34% combination DMARD therapy including 8% on
      anti-TNF therapies. Seventy-four per cent of patients with Year 1 DAS-28 < 3.2
      and 27% with DAS-28 3.2-5.1 achieved a DAS-28 < 3.2 outcome at Year 2 [odds ratio
      (OR) 7.64; 95% CI 4.6, 12.6], and 71 and 35%, respectively, at Year 3 (OR 4.49;
      95% CI 2.5, 7.9). Seventy-nine per cent of patients with a Year 1 DAS-28 < 3.2
      and 52% with DAS-28 3.2-5.1 achieved an HAQ < 1.25 at Year 2 (OR 3.47; 95% CI
      2.1, 5.6), and 81 and 47%, respectively, at Year 3 (OR 4.92; 95% CI 2.6, 9.0).
      CONCLUSIONS: In RA patients with a DAS-28 3.2-5.1 at 1 year, the likelihood of
      achieving a target low DAS-28 < 3.2, or a low HAQ, at Years 2 or 3 is poor in a
      routine care setting using conventional DMARDs according to current practice.

PMID- 21169344
TI  - Clinical correlates of sleep problems in systemic sclerosis: the prominent role
      of pain.
AB  - OBJECTIVE: Problems with sleep are common in patients with SSc and impact daily
      function. Little research, however, has examined factors associated with sleep
      disruption in SSc. Therefore, the objective of this study was to investigate
      socio-demographic and medical factors associated with sleep disruption in SSc.
      METHODS: Cross-sectional study of 70 patients from one Canadian Scleroderma
      Research Group site who were assessed with a 100-mm sleep disruption visual
      analogue scale (VAS). Patients also completed measures of pain and depressive
      symptoms and underwent clinical histories and medical examinations. Pearson's
      correlations were used to assess bivariate association of socio-demographic and
      medical variables with sleep VAS scores. Multivariable associations of socio
      demographic (Step 1) and medical (Step 2) variables with sleep VAS scores were
      assessed using hierarchical multiple linear regression. RESULTS: The mean (s.d.)
      sleep disruption VAS score was 38.5 (29.9). In bivariate analyses, sleep
      disruption was associated with marital status (r = -0.24, P = 0.042), smoking (r
      = 0.27, P = 0.025), gastrointestinal symptoms (r = 0.27, P = 0.023), breathing
      problems (r = 0.31, P = 0.009), pain (r = 0.53, P < 0.001) and symptoms of
      depression (r = 0.34, P = 0.004). In multivariate analysis, only marital status
      (standardized beta = -0.24, P = 0.049) and pain (standardized beta = 0.50, P <
      0.001) were significantly associated with sleep disruption. CONCLUSION: Sleep
      disruption scores were as high in SSc as in RA and higher than in the general
      population. Pain was robustly associated with sleep disruption. Additional
      research is needed on sleep in SSc so that well-informed sleep interventions can
      be developed and tested.

PMID- 21169345
TI  - Evidence for the efficacy of complementary and alternative medicines in the
      management of osteoarthritis: a systematic review.
AB  - Objectives. To critically evaluate the evidence regarding complementary and
      alternative medicine (CAM) taken orally or applied topically (excluding
      glucosamine and chondroitin) in the treatment of OA. Methods. Randomized clinical
      trials of OA using CAMs, in comparison with other treatments or placebo,
      published in English up to January 2009, were eligible for inclusion. They were
      identified using systematic searches of bibliographic databases and manual
      searching of reference lists. Information was extracted on outcomes, and
      statistical significance, in comparison with alternative treatment of placebo,
      and side effects were reported. The methodological quality of the primary studies
      was determined. Results. The present review found consistent evidence that
      capsaicin gel and S-adenosyl methionine were effective in the management of OA.
      There was also some consistency to the evidence that Indian Frankincense,
      methylsulphonylmethane and rose hip may be effective. For other substances with
      promising evidence, the evidence base was either insufficiently large or the
      evidence base was inconsistent. Most of the CAM compounds studied were free of
      major adverse effects. Conclusion. The major limitation in reviewing the evidence
      is the paucity of randomized controlled trials in the area: widening the evidence
      base, particularly for those compounds for which there is promising evidence,
      should be a priority for both researchers and funders.

PMID- 21169346
TI  - Light-regulated nuclear import and degradation of Arabidopsis phytochrome-A N
      terminal fragments.
AB  - The photoreceptor phytochrome-A (phyA) regulates germination and seedling
      establishment by mediating very low fluence (VLFR) and far-red high irradiance
      (FR-HIR) responses in Arabidopsis thaliana. In darkness, phyA homodimers exist in
      the biologically inactive Pr form and are localized in the cytoplasm. Light
      induces formation of the biologically active Pfr form and subsequent rapid
      nuclear import. PhyA Pfr, in contrast to the Pr form, is labile and has a half
      life of ~30 min. We produced transgenic plants in a phyA-201 null background that
      express the PHYA-yellow fluorescent protein (YFP) or the PHYA686-YFP-dimerization
      domain (DD) and PHYA686-YFP-DD-nuclear localization signal (NLS) or PHYA686-YFP
      DD-nuclear exclusion signal (NES) fusion proteins. The PHYA686-YFP fusion
      proteins contained the N-terminal domain of phyA (686 amino acid residues), a
      short DD and the YFP. Here we report that (i) PHYA686-YFP-DD fusion protein is
      imported into the nucleus in a light-dependent fashion; (ii) neither of the
      PHYA686 fusion proteins is functional in FR-HIR and nuclear VLFR; and (iii) the
      phyA-dependent, blue light-induced inhibition of hypocotyl growth is mediated by
      the PHYA686-YFP-DD-NES but not by the PHYA686-YFP-DD-NLS and PHYA686-YFP-DD
      fusion proteins. We demonstrate that (i) light induces degradation of all PHYA N
      terminal-containing fusion proteins and (ii) these N-terminal domain-containing
      fusion proteins including the constitutively nuclear PHYA686-YFP-DD-NLS and
      predominantly cytoplasmic PHYA686-YFP-DD-NES degrade at comparable rates but
      markedly more slowly than PHYA-YFP, whereas (iii) light-induced degradation of
      the native phyA is faster compared with PHYA-YFP.

PMID- 21169347
TI  - Gene structures, classification and expression models of the AP2/EREBP
      transcription factor family in rice.
AB  - We identified 163 AP2/EREBP (APETALA2/ethylene-responsive element-binding
      protein) genes in rice. We analyzed gene structures, phylogenies, domain
      duplication, genome localizations and expression profiles. Conserved amino acid
      residues and phylogeny construction using the AP2/ERF conserved domain sequence
      suggest that in rice the OsAP2/EREBP gene family can be classified broadly into
      four subfamilies [AP2, RAV (related to ABI3/VP1), DREB (dehydration-responsive
      element-binding protein) and ERF (ethylene-responsive factor)]. The chromosomal
      localizations of the OsAP2/EREBP genes indicated 20 segmental duplication events
      involving 40 genes; 58 redundant OsAP2/EREBP genes were involved in tandem
      duplication events. There were fewer introns after segmental duplication. We
      investigated expression profiles of this gene family under biotic stresses
      [infection with rice viruses such as rice stripe virus (RSV), rice tungro
      spherical virus (RTSV) and rice dwarf virus (RDV, three virus strains S, O and
      D84)], and various abiotic stresses. Symptoms of virus infection were more severe
      in RSV infection than in RTSV and RDV infection. Responses to biotic stresses are
      novel findings and these stresses enhance the ability to identify the best
      candidate genes for further functional analysis. The genes of subgroup B-5 were
      not induced under abiotic treatments whereas they were activated by the three RDV
      strains. None of the genes of subgroups A-3 were differentially expressed by any
      of the biotic stresses. Our 44K and 22K microarray results suggest that 53 and 52
      non-redundant genes in this family were up-regulated in response to biotic and
      abiotic stresses, respectively. We further examined the stress responsiveness of
      most genes by reverse transcription-PCR. The study results should be useful in
      selecting candidate genes from specific subgroups for functional analysis.

PMID- 21169348
TI  - Tumor KRAS status predicts responsiveness to panitumumab in Japanese patients
      with metastatic colorectal cancer.
AB  - OBJECTIVE: Mutation status of the KRAS gene in tumors has been shown to be a
      predictive biomarker of response to anti-epidermal growth factor receptor
      antibody therapy in patients with metastatic colorectal cancer. This
      retrospective analysis examined the association between efficacy and safety of
      the fully human anti-epidermal growth factor receptor antibody panitumumab and
      KRAS mutation status in Japanese metastatic colorectal cancer patients using data
      from two clinical trials with adherence to good clinical practices. METHODS: An
      exploratory, integrated analysis of data from KRAS evaluable patients enrolled in
      a Phase 1 study (Study 20040192) and a Phase 2 study (Study 20050216) was
      performed. Paraffin-embedded tumor samples were analyzed for KRAS status. Primary
      efficacy endpoint of this analysis was objective tumor response per modified
      response evaluation criteria in solid tumors; a key secondary endpoint was
      progression-free survival. Safety endpoints included incidence of adverse events.
      RESULTS: Tumor samples with known KRAS status were available from 8 of 13 (62%)
      metastatic colorectal cancer patients in the Phase 1 study and 16 of 53 patients
      (30%) in the Phase 2 study. Overall, 14 (58%) patients had wild-type KRAS tumors
      and 10 (42%) patients had mutated KRAS tumors. Four (17%) patients had a partial
      response; all responders had tumors with wild-type KRAS. Results of all secondary
      efficacy endpoints also favored patients with wild-type KRAS. Treatment-related
      adverse events were predominantly mild to moderate and skin related, and were
      similar between patients with tumors with wild-type and mutated KRAS in this
      small patient population. CONCLUSIONS: Mutated KRAS status in tumors of Japanese
      patients with metastatic colorectal cancer is associated with lack of response to
      panitumumab therapy.

PMID- 21169349
TI  - The clinical impact of the classification of carcinoma in situ on tumor
      recurrence and their clinical course in patients with bladder tumor.
AB  - OBJECTIVE: To evaluate recurrence and clinical course of bladder carcinoma in
      situ according to the current carcinoma in situ classification by analyzing the
      patients with diagnosed carcinoma in situ in our hospital. METHODS: Between
      January 1993 and September 2008, 93 patients were initially diagnosed with
      bladder carcinoma in situ in our hospital. All specimens underwent an additional
      review by one uro-pathologist. Primary, secondary and concurrent carcinoma in
      situ were found in 26, 21 and 46 patients, respectively. Sixty-nine patients
      (74.2%) underwent bacillus Calmette-Guerin instillation therapy. RESULTS: The
      multivariate analysis determined that the secondary carcinoma in situ and the
      absence of bacillus Calmette-Guerin therapy were the independent unfavorable risk
      factors for tumor recurrence. The 5-year recurrence-free survival rates on
      primary, concurrent and secondary carcinoma in situ were 60.9, 63.2 and 25.4%,
      respectively, and the differences between secondary and primary carcinoma in
      situ, and secondary and concurrent were significant (P= 0.023 and P= 0.006,
      respectively). During the median follow-up period of 47 months, 19 patients had
      tumor recurrence in the bladder after the first bacillus Calmette-Guerin therapy,
      and 13 of them were treated with a second bacillus Calmette-Guerin therapy. After
      the second bacillus Calmette-Guerin therapy six patients eventually had distant
      metastasis and three had upper tract recurrence, whereas totally four had a tumor
      free status after the second bacillus Calmette-Guerin therapy. CONCLUSIONS: The
      first induction course of bacillus Calmette-Guerin therapy proved to be effective
      for the prevention of bladder cancer recurrence, however, the efficacy of a
      second bacillus Calmette-Guerin therapy on a recurrent tumor was somewhat
      limited.

PMID- 21169350
TI  - Wandering through the laboratory.

PMID- 21169351
TI  - Identification through combinatorial random and rational mutagenesis of a
      substrate-interacting exosite in the gamma domain of streptokinase.
AB  - To identify new structure-function correlations in the gamma domain of
      streptokinase, mutants were generated by error-prone random mutagenesis of the
      gamma domain and its adjoining region in the beta domain followed by functional
      screening specifically for substrate plasminogen activation. Single-site mutants
      derived from various multipoint mutation clusters identified the importance of
      discrete residues in the gamma domain that are important for substrate
      processing. Among the various residues, aspartate at position 328 was identified
      as critical for substrate human plasminogen activation through extensive
      mutagenesis of its side chain, namely D328R, D328H, D328N, and D328A. Other
      mutants found to be important in substrate plasminogen activation were, namely,
      R319H, N339S, K334A, K334E, and L335Q. When examined for their 1:1 interaction
      with human plasmin, these mutants were found to retain the native-like high
      affinity for plasmin and also to generate amidolytic activity with partner
      plasminogen in a manner similar to wild type streptokinase. Moreover, cofactor
      activities of the mutants precomplexed with plasmin against microplasminogen as
      the substrate as well as in silico modeling studies suggested that the region 315
      340 of the gamma domain interacts with the serine protease domain of the
      macromolecular substrate. Overall, our results identify the presence of a
      substrate specific exosite in the gamma domain of streptokinase.

PMID- 21169352
TI  - Structural analysis of Mg2+ and Ca2+ binding, myristoylation, and dimerization of
      the neuronal calcium sensor and visinin-like protein 1 (VILIP-1).
AB  - Visinin-like protein 1 (VILIP-1) belongs to the neuronal calcium sensor family of
      Ca(2+)-myristoyl switch proteins that regulate signal transduction in the brain
      and retina. Here we analyze Ca(2+) and Mg(2+) binding, characterize metal-induced
      conformational changes, and determine structural effects of myristoylation and
      dimerization. Mg(2+) binds functionally to VILIP-1 at EF3 (DeltaH = +1.8 kcal/mol
      and K(D) = 20 MUM). Unmyristoylated VILIP-1 binds two Ca(2+) sequentially at EF2
      and EF3 (K(EF3) = 0.1 MUM and K(EF2) = 1-4 MUM), whereas myristoylated VILIP-1
      binds two Ca(2+) with lower affinity (K(D) = 1.2 MUM) and positive cooperativity
      (Hill slope = 1.5). NMR assignments and structural analysis indicate that Ca(2+)
      free VILIP-1 contains a sequestered myristoyl group like that of recoverin. NMR
      resonances of the attached myristate exhibit Ca(2+)-dependent chemical shifts and
      NOE patterns consistent with Ca(2+)-induced extrusion of the myristate. VILIP-1
      forms a dimer in solution independent of Ca(2+) and myristoylation. The
      dimerization site is composed of residues in EF4 and the loop region between EF3
      and EF4, confirmed by mutagenesis. We present the structure of the VILIP-1 dimer
      and a Ca(2+)-myristoyl switch to provide structural insights into Ca(2+)-induced
      trafficking of nicotinic acetylcholine receptors.

PMID- 21169353
TI  - Atomic structure of salutaridine reductase from the opium poppy (Papaver
      somniferum).
AB  - The opium poppy (Papaver somniferum L.) is one of the oldest known medicinal
      plants. In the biosynthetic pathway for morphine and codeine, salutaridine is
      reduced to salutaridinol by salutaridine reductase (SalR; EC 1.1.1.248) using
      NADPH as coenzyme. Here, we report the atomic structure of SalR to a resolution
      of ~1.9 A in the presence of NADPH. The core structure is highly homologous to
      other members of the short chain dehydrogenase/reductase family. The major
      difference is that the nicotinamide moiety and the substrate-binding pocket are
      covered by a loop (residues 265-279), on top of which lies a large "flap"-like
      domain (residues 105-140). This configuration appears to be a combination of the
      two common structural themes found in other members of the short chain
      dehydrogenase/reductase family. Previous modeling studies suggested that
      substrate inhibition is due to mutually exclusive productive and nonproductive
      modes of substrate binding in the active site. This model was tested via site
      directed mutagenesis, and a number of these mutations abrogated substrate
      inhibition. However, the atomic structure of SalR shows that these mutated
      residues are instead distributed over a wide area of the enzyme, and many are not
      in the active site. To explain how residues distal to the active site might
      affect catalysis, a model is presented whereby SalR may undergo significant
      conformational changes during catalytic turnover.

PMID- 21169354
TI  - Carboxylate shifts steer interquinone electron transfer in photosynthesis.
AB  - Understanding the mechanisms of electron transfer (ET) in photosynthetic reaction
      centers (RCs) may inspire novel catalysts for sunlight-driven fuel production.
      The electron exit pathway of type II RCs comprises two quinone molecules working
      in series and in between a non-heme iron atom with a carboxyl ligand (bicarbonate
      in photosystem II (PSII), glutamate in bacterial RCs). For decades, the
      functional role of the iron has remained enigmatic. We tracked the iron site
      using microsecond-resolution x-ray absorption spectroscopy after laser-flash
      excitation of PSII. After formation of the reduced primary quinone, Q(A)(-), the
      x-ray spectral changes revealed a transition (t1/2 ~ 150 MUs) from a bidentate to
      a monodentate coordination of the bicarbonate at the Fe(II) (carboxylate shift),
      which reverted concomitantly with the slower ET to the secondary quinone Q(B). A
      redox change of the iron during the ET was excluded. Density-functional theory
      calculations corroborated the carboxylate shift both in PSII and bacterial RCs
      and disclosed underlying changes in electronic configuration. We propose that the
      iron-carboxyl complex facilitates the first interquinone ET by optimizing charge
      distribution and hydrogen bonding within the Q(A)FeQ(B) triad for high yield Q(B)
      reduction. Formation of a specific priming intermediate by nuclear
      rearrangements, setting the stage for subsequent ET, may be a common motif in
      reactions of biological redox cofactors.

PMID- 21169355
TI  - Andrographolide enhances nuclear factor-kappaB subunit p65 Ser536
      dephosphorylation through activation of protein phosphatase 2A in vascular smooth
      muscle cells.
AB  - Recent studies have demonstrated that transcription factor nuclear factor (NF)
      kappaB inhibition may contribute to the protective anti-inflammatory actions of
      andrographolide, an abundant component of plants of the genus Andrographis.
      However, the precise mechanism by which andrographolide inhibits NF-kappaB
      signaling remains unclear. We thus investigated the mechanism involved in
      andrographolide suppression of NF-kappaB signaling in rat vascular smooth muscle
      cells (VSMCs) exposed to proinflammatory stimuli, LPS, and IFN-gamma.
      Andrographolide was shown to suppress LPS/IFN-gamma-induced inducible nitric
      oxide synthase and matrix metalloprotease 9 expression in rat VSMCs.
      Andrographolide also inhibited LPS/IFN-gamma-induced p65 nuclear translocation,
      DNA binding activity, p65 Ser(536) phosphorylation, and NF-kappaB reporter
      activity. However, IKK phosphorylation and downstream inhibitory kappaBalpha
      phosphorylation and degradation were not altered by the presence of
      andrographolide in LPS/IFN-gamma-stimulated VSMCs. These andrographolide
      inhibitory actions could be prevented by selective inhibition of neutral
      sphingomyelinase and protein phosphatase 2A (PP2A). Furthermore, andrographolide
      was demonstrated to increase ceramide formation and PP2A activity in VSMCs and to
      inhibit neointimal formation in rat carotid injury models. These results suggest
      that andrographolide caused neutral sphingomyelinase-mediated ceramide formation
      and PP2A activation to dephosphorylate p65 Ser(536), leading to NF-kappaB
      inactivation and subsequent inducible nitric-oxide synthase down-regulation in
      rat VSMCs stimulated by LPS and IFN-gamma.

PMID- 21169356
TI  - New alkaloid antibiotics that target the DNA topoisomerase I of Streptococcus
      pneumoniae.
AB  - Streptococcus pneumoniae has two type II DNA-topoisomerases (DNA-gyrase and DNA
      topoisomerase IV) and a single type I enzyme (DNA-topoisomerase I, TopA), as
      demonstrated here. Although fluoroquinolones target type II enzymes, antibiotics
      efficiently targeting TopA have not yet been reported. Eighteen alkaloids (seven
      aporphine and 11 phenanthrenes) were semisynthesized from boldine and used to
      test inhibition both of TopA activity and of cell growth. Two phenanthrenes
      (seconeolitsine and N-methyl-seconeolitsine) effectively inhibited both TopA
      activity and cell growth at equivalent concentrations (~17 MUM). Evidence for in
      vivo TopA targeting by seconeolitsine was provided by the protection of growth
      inhibition in a S. pneumoniae culture in which the enzyme was overproduced.
      Additionally, hypernegative supercoiling was observed in an internal plasmid
      after drug treatment. Furthermore, a model of pneumococcal TopA was made based on
      the crystal structure of Escherichia coli TopA. Docking calculations indicated
      strong interactions of the alkaloids with the nucleotide-binding site in the
      closed protein conformation, which correlated with their inhibitory effect.
      Finally, although seconeolitsine and N-methyl-seconeolitsine inhibited TopA and
      bacterial growth, they did not affect human cell viability. Therefore, these new
      alkaloids can be envisaged as new therapeutic candidates for the treatment of S.
      pneumoniae infections resistant to other antibiotics.

PMID- 21169357
TI  - KRAS(G12V) enhances proliferation and initiates myelomonocytic differentiation in
      human stem/progenitor cells via intrinsic and extrinsic pathways.
AB  - In human hematopoietic malignancies, RAS mutations are frequently observed. Yet,
      little is known about signal transduction pathways that mediate KRAS-induced
      phenotypes in human CD34(+) stem/progenitor cells. When cultured on bone marrow
      stroma, we observed that KRAS(G12V)-transduced cord blood (CB) CD34(+) cells
      displayed a strong proliferative advantage over control cells, which coincided
      with increased early cobblestone (CAFC) formation and induction of myelomonocytic
      differentiation. However, the KRAS(G12V)-induced proliferative advantage was
      transient. By week three no progenitors remained in KRAS(G12V)-transduced
      cultures and cells were all terminally differentiated into monocytes/macrophages.
      In line with these results, LTC-IC frequencies were strongly reduced. Both the
      ERK and p38 MAPK pathways, but not JNK, were activated by KRAS(G12V) and we
      observed that proliferation and CAFC formation were mediated via ERK, while
      differentiation was predominantly mediated via p38. Interestingly, we observed
      that KRAS(G12V)-induced proliferation and CAFC formation, but not
      differentiation, were largely mediated via secreted factors, since these
      phenotypes could be recapitulated by treating non-transduced cells with
      conditioned medium harvested from KRAS(G12V)-transduced cultures. Multiplex
      cytokine arrays and genome-wide gene expression profiling were performed to gain
      further insight into the mechanisms by which oncogenic KRAS(G12V) can contribute
      to the process of leukemic transformation. Thus, angiopoietin-like 6 (ANGPTL6)
      was identified as an important factor in the KRAS(G12V) secretome that enhanced
      proliferation of human CB CD34(+) cells.

PMID- 21169358
TI  - Arrestin-rhodopsin binding stoichiometry in isolated rod outer segment membranes
      depends on the percentage of activated receptors.
AB  - In the rod cell of the retina, arrestin is responsible for blocking signaling of
      the G-protein-coupled receptor rhodopsin. The general visual signal transduction
      model implies that arrestin must be able to interact with a single light
      activated, phosphorylated rhodopsin molecule (Rho*P), as would be generated at
      physiologically relevant low light levels. However, the elongated bi-lobed
      structure of arrestin suggests that it might be able to accommodate two rhodopsin
      molecules. In this study, we directly addressed the question of binding
      stoichiometry by quantifying arrestin binding to Rho*P in isolated rod outer
      segment membranes. We manipulated the "photoactivation density," i.e. the
      percentage of active receptors in the membrane, with the use of a light flash or
      by partially regenerating membranes containing phosphorylated opsin with 11-cis
      retinal. Curiously, we found that the apparent arrestin-Rho*P binding
      stoichiometry was linearly dependent on the photoactivation density, with one-to
      one binding at low photoactivation density and one-to-two binding at high
      photoactivation density. We also observed that, irrespective of the
      photoactivation density, a single arrestin molecule was able to stabilize the
      active metarhodopsin II conformation of only a single Rho*P. We hypothesize that,
      although arrestin requires at least a single Rho*P to bind the membrane, a single
      arrestin can actually interact with a pair of receptors. The ability of arrestin
      to interact with heterogeneous receptor pairs composed of two different photo
      intermediate states would be well suited to the rod cell, which functions at low
      light intensity but is routinely exposed to several orders of magnitude more
      light.

PMID- 21169359
TI  - Anti-group A streptococcal vaccine epitope: structure, stability, and its ability
      to interact with HLA class II molecules.
AB  - Streptococcus pyogenes infections remain a health problem in several countries
      due to poststreptococcal sequelae. We developed a vaccine epitope (StreptInCor)
      composed of 55 amino acids residues of the C-terminal portion of the M protein
      that encompasses both T and B cell protective epitopes. The nuclear magnetic
      resonance (NMR) structure of the StreptInCor peptide showed that the structure
      was composed of two microdomains linked by an 18-residue alpha-helix. A chemical
      stability study of the StreptInCor folding/unfolding process using far-UV
      circular dichroism showed that the structure was chemically stable with respect
      to pH and the concentration of urea. The T cell epitope is located in the first
      microdomain and encompasses 11 out of the 18 alpha-helix residues, whereas the B
      cell epitope is in the second microdomain and showed no alpha-helical structure.
      The prediction of StreptInCor epitope binding to different HLA class II molecules
      was evaluated based on an analysis of the 55 residues and the theoretical
      possibilities for the processed peptides to fit into the P1, P4, P6, and P9
      pockets in the groove of several HLA class II molecules. We observed 7 potential
      sites along the amino acid sequence of StreptInCor that were capable of
      recognizing HLA class II molecules (DRB1*, DRB3*, DRB4*, and DRB5*). StreptInCor
      overlapping peptides induced cellular and humoral immune responses of individuals
      bearing different HLA class II molecules and could be considered as a universal
      vaccine epitope.

PMID- 21169360
TI  - Endothelin-1 increases collagen accumulation in renal mesangial cells by
      stimulating a chemokine and cytokine autocrine signaling loop.
AB  - Endothelin-1 (ET-1), a potent vasoconstrictor, has been implicated in the
      pathogenesis of collagen accumulation, extracellular matrix remodeling, and renal
      and cardiac fibrosis in diabetes. However, the mechanism by which ET-1 promotes
      collagen accumulation remains unclear. Here, we analyzed the gene expression
      profile of ET-1-stimulated mesangial cells to identify determinants of collagen
      accumulation. In human mesangial cells (a microvascular pericyte that secretes
      excess collagen in diabetic glomerulosclerosis), ET-1 increased mRNA and protein
      for MCP-1 (macrophage chemoattractant protein-1) and IL-6. ET-1-induced MCP-1 and
      IL-6 mRNAs and proteins were blocked by an ET(A) (but not ET(B)) receptor
      antagonist. ET-1/ET(A) receptor signaling evoked a 7.4-fold increase in collagen
      accumulation. Exogenous addition of either recombinant MCP-1 or IL-6 increased
      collagen accumulation by 3.5-fold. Co-stimulation with both MCP-1 and IL-6 did
      not elevate collagen accumulation further. Neither an MCP-1-neutralizing antibody
      nor an MCP-1 receptor antagonist inhibited ET-1-induced collagen accumulation.
      Similarly, neutralizing antibodies against IL-6 or the gp130 subunit of the IL-6
      receptor did not attenuate ET-1-induced collagen accumulation. However, co
      incubation with MCP-1- and IL-6-neutralizing antibodies inhibited ET-1-induced
      collagen accumulation by 52%, suggesting a robust autocrine loop wherein MCP-1
      and IL-6 are redundant. Taken together, these results demonstrate that an
      autocrine signaling loop involving MCP-1 and IL-6 contributes to ET-1-induced
      collagen accumulation.

PMID- 21169361
TI  - Dual regulation of RA-RhoGAP activity by phosphatidic acid and Rap1 during
      neurite outgrowth.
AB  - During neurite outgrowth, Rho small G protein activity is spatiotemporally
      regulated to organize the neurite sprouting, extension, and branching. We have
      previously identified a potent Rho GTPase-activating protein (GAP), RA-RhoGAP, as
      a direct downstream target of Rap1 small G protein in the neurite outgrowth. In
      addition to the Ras-associating (RA) domain for Rap1 binding, RA-RhoGAP has the
      pleckstrin homology (PH) domain for lipid binding. Here, we showed that
      phosphatidic acid (PA) bound to the PH domain and enhanced GAP activity for Rho.
      RA-RhoGAP induced extension of neurite in a diacylglycerol kinase-mediated
      synthesis of the PA-dependent manner. Knockdown of RA-RhoGAP reduced the
      diacylglycerol kinase-induced neurite extension. In contrast to the effect of the
      RA domain, the PH domain was specifically involved in the neurite extension, not
      in the sprouting and branching. These results indicate that PA and Rap1
      cooperatively regulate RA-RhoGAP activity for promoting neurite outgrowth.

PMID- 21169362
TI  - Homology-based identification of capsid determinants that protect HIV1 from human
      TRIM5alpha restriction.
AB  - The tropism of retroviruses relies on their ability to exploit cellular factors
      for their replication as well as to avoid host-encoded inhibitory activities such
      as TRIM5alpha. N-tropic murine leukemia virus is sensitive to human TRIM5alpha
      (huTRIM5alpha) restriction, whereas human immunodeficiency virus type 1 (HIV1)
      escapes this antiviral factor. We previously revealed that mutation of four
      critical amino acid residues within the capsid can render murine leukemia virus
      resistant to huTRIM5alpha. Here, we exploit the high degree of conservation in
      the tertiary structure of retroviral capsids to map the corresponding positions
      on the HIV1 capsid. We then demonstrated that, when changes were introduced at
      some of these positions, HIV1 becomes sensitive to huTRIM5alpha restriction, a
      phenomenon reinforced by additionally mutating the nearby cyclophilin A binding
      loop of the viral protein. These results indicate that retroviruses have evolved
      similar mechanisms to escape TRIM5alpha restriction via the interference of
      structurally homologous determinants in the viral capsid.

PMID- 21169363
TI  - Discovery and structural characterization of fucosylated oligomannosidic N
      glycans in mushrooms.
AB  - L-fucose is a common constituent of Asn-linked glycans in vertebrates,
      invertebrates, and plants, but in fungal glycoproteins, fucose has not been found
      so far. However, by mass spectrometry we detected N-glycans and O-glycans
      containing one to six deoxyhexose residues in fruit bodies of several
      basidiomycetes. The N-glycans of chanterelles (Cantharellus cibarius) contained a
      deoxyhexose chromatographically identical to fucose and sensitive to alpha-L
      fucosidase. Analysis of individual glycan species by tandem MS, glycosidase
      digestion, and finally (1)H NMR revealed the presence of L-fucose in alpha1,6
      linkage to an alpha1,6-mannose of oligomannosidic N-glycans. The substitution by
      alpha1,6-mannose of alpha1,2-mannosyl residues of the canonical precursor
      structure was yet another hitherto unknown modification. No indication for the
      occurrence of yet other modifications, e.g. bisecting N-acetylglucosamine, was
      seen. Besides fucosylated N-glycans, short O-linked mannan chains substituted
      with fucose were present on chanterelle proteins. Although undiscovered so far, L
      fucose appears to represent a prominent feature of protein-linked glycans in the
      fungal kingdom.

PMID- 21169364
TI  - A mechanism for single-stranded DNA-binding protein (SSB) displacement from
      single-stranded DNA upon SSB-RecO interaction.
AB  - Displacement of single-stranded DNA (ssDNA)-binding protein (SSB) from ssDNA is
      necessary for filament formation of RecA on ssDNA to initiate homologous
      recombination. The interaction between RecO and SSB is considered to be important
      for SSB displacement; however, the interaction has not been characterized at the
      atomic level. In this study, to clarify the mechanism underlying SSB displacement
      from ssDNA upon RecO binding, we examined the interaction between Thermus
      thermophilus RecO and cognate SSB by NMR analysis. We found that SSB interacts
      with the C-terminal positively charged region of RecO. Based on this result, we
      constructed some RecO mutants. The R127A mutant had considerably decreased
      binding affinity for SSB and could not anneal SSB-coated ssDNAs. Further, the
      mutant in the RecOR complex prevented the recovery of ssDNA-dependent ATPase
      activity of RecA from inhibition by SSB. These results indicated that the region
      surrounding Arg-127 is the binding site of SSB. We also performed NMR analysis
      using the C-terminal peptide of SSB and found that the acidic region of SSB is
      involved in the interaction with RecO, as seen in other protein-SSB interactions.
      Taken together with the findings of previous studies, we propose a model for SSB
      displacement from ssDNA where the acidic C-terminal region of SSB weakens the
      ssDNA binding affinity of SSB when the dynamics of the C-terminal region are
      suppressed by interactions with other proteins, including RecO.

PMID- 21169365
TI  - Preferential repair of oxidized base damage in the transcribed genes of mammalian
      cells.
AB  - Preferential repair of bulky DNA adducts from the transcribed genes via
      nucleotide excision repair is well characterized in mammalian cells. However,
      definitive evidence is lacking for similar repair of oxidized bases, the major
      endogenous DNA lesions. Here we show that the oxidized base-specific human DNA
      glycosylase NEIL2 associates with RNA polymerase II and the transcriptional
      regulator heterogeneous nuclear ribonucleoprotein-U (hnRNP-U), both in vitro and
      in cells. NEIL2 immunocomplexes from cell extracts preferentially repaired the
      mutagenic cytosine oxidation product 5-hydroxyuracil in the transcribed strand.
      In a reconstituted system, we also observed NEIL2-initiated transcription
      dependent base excision repair of 5-hydroxyuracil in the transcribed strand, with
      hnRNP-U playing a critical role. Chromatin
      immunoprecipitation/reimmunoprecipitation studies showed association of NEIL2,
      RNA polymerase II, and hnRNP-U on transcribed but not on transcriptionally silent
      genes. Furthermore, NEIL2-depleted cells accumulated more DNA damage in active
      than in silent genes. These results strongly support the preferential role of
      NEIL2 in repairing oxidized bases in the transcribed genes of mammalian cells.

PMID- 21169366
TI  - NADPH-dependent reductases involved in the detoxification of reactive carbonyls
      in plants.
AB  - Reactive carbonyls, especially alpha,beta-unsaturated carbonyls produced through
      lipid peroxidation, damage biomolecules such as proteins and nucleotides;
      elimination of these carbonyls is therefore essential for maintaining cellular
      homeostasis. In this study, we focused on an NADPH-dependent detoxification of
      reactive carbonyls in plants and explored the enzyme system involved in this
      detoxification process. Using acrolein (CH(2) = CHCHO) as a model alpha,beta
      unsaturated carbonyl, we purified a predominant NADPH-dependent acrolein-reducing
      enzyme from cucumber leaves, and we identified the enzyme as an alkenal/one
      oxidoreductase (AOR) catalyzing reduction of an alpha,beta-unsaturated bond.
      Cloning of cDNA encoding AORs revealed that cucumber contains two distinct AORs,
      chloroplastic AOR and cytosolic AOR. Homologs of cucumber AORs were found among
      various plant species, including Arabidopsis, and we confirmed that a homolog of
      Arabidopsis (At1g23740) also had AOR activity. Phylogenetic analysis showed that
      these AORs belong to a novel class of AORs. They preferentially reduced
      alpha,beta-unsaturated ketones rather than alpha,beta-unsaturated aldehydes.
      Furthermore, we selected candidates of other classes of enzymes involved in NADPH
      dependent reduction of carbonyls based on the bioinformatic information, and we
      found that an aldo-keto reductase (At2g37770) and aldehyde reductases (At1g54870
      and At3g04000) were implicated in the reduction of an aldehyde group of saturated
      aldehydes and methylglyoxal as well as alpha,beta-unsaturated aldehydes in
      chloroplasts. These results suggest that different classes of NADPH-dependent
      reductases cooperatively contribute to the detoxification of reactive carbonyls.

PMID- 21169368
TI  - Where have the fluxes gone?

PMID- 21169367
TI  - N-glycans of Phaeodactylum tricornutum diatom and functional characterization of
      its N-acetylglucosaminyltransferase I enzyme.
AB  - N-glycosylation, a major co- and post-translational event in the synthesis of
      proteins in eukaryotes, is unknown in aquatic photosynthetic microalgae. In this
      paper, we describe the N-glycosylation pathway in the diatom Phaeodactylum
      tricornutum. Bio-informatic analysis of its genome revealed the presence of a
      complete set of sequences potentially encoding for proteins involved in the
      synthesis of the lipid-linked Glc(3)Man(9)GlcNAc(2)-PP-dolichol N-glycan, some
      subunits of the oligosaccharyltransferase complex, as well as endoplasmic
      reticulum glucosidases and chaperones required for protein quality control and,
      finally, the alpha-mannosidase I involved in the trimming of the N-glycan
      precursor into Man-5 N-glycan. Moreover, one N-acetylglucosaminyltransferase I, a
      Golgi glycosyltransferase that initiates the synthesis of complex type N-glycans,
      was predicted in the P. tricornutum genome. We demonstrated that this gene
      encodes for an active N-acetylglucosaminyltransferase I, which is able to restore
      complex type N-glycans maturation in the Chinese hamster ovary Lec1 mutant,
      defective in its endogeneous N-acetylglucosaminyltransferase I. Consistent with
      these data, the structural analyses of N-linked glycans demonstrated that P.
      tricornutum proteins carry mainly high mannose type N-glycans ranging from Man-5
      to Man-9. Although representing a minor glycan population, paucimannose N-glycans
      were also detected, suggesting the occurrence of an N
      acetylglucosaminyltransferase I-dependent maturation of N-glycans in this diatom.

PMID- 21169370
TI  - Barriers and facilitators to implementing screening and brief intervention for
      alcohol misuse: a systematic review of qualitative evidence.
AB  - BACKGROUND: This review aimed to synthesize qualitative evidence for barriers and
      facilitators to effective implementation of screening and brief intervention for
      alcohol misuse in adults and children over 10 years. METHODS: A search of medical
      and social science databases was carried out and augmented by hand-searching of
      reference lists and contents of key journals. Qualitative evidence was
      synthesized thematically. RESULTS: A total of 47 papers varying in design and
      quality were included in the review. Most evaluated implementation in primary
      care settings. Implementation was reported to be limited by lack of resources,
      training and support from management, as well as workload. The appropriateness of
      context in which discussions take place was reported as an acceptability factor
      for patients and practitioners. Health professionals require sufficient knowledge
      about alcohol guidelines and risk in order to implement screening and
      intervention to those most in need. CONCLUSIONS: Whilst brief screening and brief
      intervention have been shown to be effective in some settings, this review has
      identified a number of barriers and facilitators to implementation. Adequate
      resources, training and the identification of those at risk without stereotyping
      are the main facilitators in primary care. More research is needed to assess
      implementation in other settings.

PMID- 21169371
TI  - Using non-uniform read distribution models to improve isoform expression
      inference in RNA-Seq.
AB  - MOTIVATION: RNA-Seq technology based on next-generation sequencing provides the
      unprecedented ability of studying transcriptomes at high resolution and accuracy,
      and the potential of measuring expression of multiple isoforms from the same gene
      at high precision. Solved by maximum likelihood estimation, isoform expression
      can be inferred in RNA-Seq using statistical models based on the assumption that
      sequenced reads are distributed uniformly along transcripts. Modification of the
      model is needed when considering situations where RNA-Seq data do not follow
      uniform distribution. RESULTS: We proposed two curves, the global bias curve
      (GBC) and the local bias curves (LBCs), to describe the non-uniformity of read
      distributions for all genes in a transcriptome and for each gene, respectively.
      Incorporating the bias curves into the uniform read distribution (URD) model, we
      introduced non-URD (N-URD) models to infer isoform expression levels. On a series
      of systematic simulation studies, the proposed models outperform the original
      model in recovering major isoforms and the expression ratio of alternative
      isoforms. We also applied the new model to real RNA-Seq datasets and found that
      its inferences on expression ratios of alternative isoforms are more reasonable.
      The experiments indicate that incorporating N-URD information can improve the
      accuracy in modeling and inferring isoform expression in RNA-Seq.

PMID- 21169372
TI  - Identifying cancer driver genes in tumor genome sequencing studies.
AB  - MOTIVATION: Major tumor sequencing projects have been conducted in the past few
      years to identify genes that contain 'driver' somatic mutations in tumor samples.
      These genes have been defined as those for which the non-silent mutation rate is
      significantly greater than a background mutation rate estimated from silent
      mutations. Several methods have been used for estimating the background mutation
      rate. RESULTS: We propose a new method for identifying cancer driver genes, which
      we believe provides improved accuracy. The new method accounts for the functional
      impact of mutations on proteins, variation in background mutation rate among
      tumors and the redundancy of the genetic code. We reanalyzed sequence data for
      623 candidate genes in 188 non-small cell lung tumors using the new method. We
      found several important genes like PTEN, which were not deemed significant by the
      previous method. At the same time, we determined that some genes previously
      reported as drivers were not significant by the new analysis because mutations in
      these genes occurred mainly in tumors with large background mutation rates.
      AVAILABILITY: The software is available at:
      http://linus.nci.nih.gov/Data/YounA/software.zip.

PMID- 21169373
TI  - SAIL--a software system for sample and phenotype availability across biobanks and
      cohorts.
AB  - SUMMARY: The Sample avAILability system-SAIL-is a web based application for
      searching, browsing and annotating biological sample collections or biobank
      entries. By providing individual-level information on the availability of
      specific data types (phenotypes, genetic or genomic data) and samples within a
      collection, rather than the actual measurement data, resource integration can be
      facilitated. A flexible data structure enables the collection owners to provide
      descriptive information on their samples using existing or custom vocabularies.
      Users can query for the available samples by various parameters combining them
      via logical expressions. The system can be scaled to hold data from millions of
      samples with thousands of variables. AVAILABILITY: SAIL is available under Aferro
      GPL open source license: https://github.com/sail.

PMID- 21169374
TI  - Multi-level mixed effects models for bead arrays.
AB  - MOTIVATION: Bead arrays are becoming a popular platform for high-throughput
      expression arrays. However, the number of the beads targeting a transcript and
      the variation of their intensities differ from sample to sample in these arrays.
      This property results in different accuracy of expression intensities of a
      transcript across arrays. RESULTS: We provide evidence, with publicly available
      spike-in data, that the false discovery rate of differential expression is
      reduced by modeling bead-level variability with a multi-level mixed effects
      model. We compare the performance of our proposed model to existing analysis
      methods for bead arrays: the unweighted t-test and other weighted methods.
      Additionally, we provide theoretical insights into when the multi-level mixed
      effects model outperforms other methods. Finally, we provide a software program
      for differential expression analysis using the multi-level mixed effects model
      that analyzes tens of thousands of genes efficiently. AVAILABILITY: The software
      program is freely available on web at
      http://ephpublic.aecom.yu.edu/sites/rkim/Supplementary.

PMID- 21169376
TI  - DROP: an SVM domain linker predictor trained with optimal features selected by
      random forest.
AB  - MOTIVATION: Biologically important proteins are often large, multidomain
      proteins, which are difficult to characterize by high-throughput experimental
      methods. Efficient domain/boundary predictions are thus increasingly required in
      diverse area of proteomics research for computationally dissecting proteins into
      readily analyzable domains. RESULTS: We constructed a support vector machine
      (SVM)-based domain linker predictor, DROP (Domain linker pRediction using OPtimal
      features), which was trained with 25 optimal features. The optimal combination of
      features was identified from a set of 3000 features using a random forest
      algorithm complemented with a stepwise feature selection. DROP demonstrated a
      prediction sensitivity and precision of 41.3 and 49.4%, respectively. These
      values were over 19.9% higher than those of control SVM predictors trained with
      non-optimized features, strongly suggesting the efficiency of our feature
      selection method. In addition, the mean NDO-Score of DROP for predicting novel
      domains in seven CASP8 FM multidomain proteins was 0.760, which was higher than
      any of the 12 published CASP8 DP servers. Overall, these results indicate that
      the SVM prediction of domain linkers can be improved by identifying optimal
      features that best distinguish linker from non-linker regions.

PMID- 21169375
TI  - Adjustment for local ancestry in genetic association analysis of admixed
      populations.
AB  - MOTIVATION: Admixed populations offer a unique opportunity for mapping diseases
      that have large disease allele frequency differences between ancestral
      populations. However, association analysis in such populations is challenging
      because population stratification may lead to association with loci unlinked to
      the disease locus. METHODS AND RESULTS: We show that local ancestry at a test
      single nucleotide polymorphism (SNP) may confound with the association signal and
      ignoring it can lead to spurious association. We demonstrate theoretically that
      adjustment for local ancestry at the test SNP is sufficient to remove the
      spurious association regardless of the mechanism of population stratification,
      whether due to local or global ancestry differences among study subjects;
      however, global ancestry adjustment procedures may not be effective. We further
      develop two novel association tests that adjust for local ancestry. Our first
      test is based on a conditional likelihood framework which models the distribution
      of the test SNP given disease status and flanking marker genotypes. A key
      advantage of this test lies in its ability to incorporate different directions of
      association in the ancestral populations. Our second test, which is
      computationally simpler, is based on logistic regression, with adjustment for
      local ancestry proportion. We conducted extensive simulations and found that the
      Type I error rates of our tests are under control; however, the global adjustment
      procedures yielded inflated Type I error rates when stratification is due to
      local ancestry difference.

PMID- 21169377
TI  - ABMapper: a suffix array-based tool for multi-location searching and splice
      junction mapping.
AB  - Sequencing reads generated by RNA-sequencing (RNA-seq) must first be mapped back
      to the genome through alignment before they can be further analyzed. Current fast
      and memory-saving short-read mappers could give us a quick view of the
      transcriptome. However, they are neither designed for reads that span across
      splice junctions nor for repetitive reads, which can be mapped to multiple
      locations in the genome (multi-reads). Here, we describe a new software package:
      ABMapper, which is specifically designed for exploring all putative locations of
      reads that are mapped to splice junctions or repetitive in nature. AVAILABILITY
      AND IMPLEMENTATION: The software is freely available at:
      http://abmapper.sourceforge.net/. The software is written in C++ and PERL. It
      runs on all major platforms and operating systems including Windows, Mac OS X and
      LINUX.

PMID- 21169378
TI  - phangorn: phylogenetic analysis in R.
AB  - SUMMARY: phangorn is a package for phylogenetic reconstruction and analysis in
      the R language. Previously it was only possible to estimate phylogenetic trees
      with distance methods in R. phangorn, now offers the possibility of
      reconstructing phylogenies with distance based methods, maximum parsimony or
      maximum likelihood (ML) and performing Hadamard conjugation. Extending the
      general ML framework, this package provides the possibility of estimating mixture
      and partition models. Furthermore, phangorn offers several functions for
      comparing trees, phylogenetic models or splits, simulating character data and
      performing congruence analyses. AVAILABILITY: phangorn can be obtained through
      the CRAN homepage http://cran.r-project.org/web/packages/phangorn/index.html.
      phangorn is licensed under GPL 2.

PMID- 21169379
TI  - Lipid Data Analyzer: unattended identification and quantitation of lipids in LC
      MS data.
AB  - MOTIVATION: The accurate measurement of the lipidome permits insights into
      physiological and pathological processes. Of the present high-throughput
      technologies, LC-MS especially bears potential of monitoring quantitative changes
      in hundreds of lipids simultaneously. In order to extract valuable information
      from huge amount of mass spectrometry data, the aid of automated, reliable,
      highly sensitive and specific analysis algorithms is indispensable. RESULTS: We
      present here a novel approach for the quantitation of lipids in LC-MS data. The
      new algorithm obtains its analytical power by two major innovations: (i) a 3D
      algorithm that confines the peak borders in m/z and time direction and (ii) the
      use of the theoretical isotopic distribution of an analyte as selection/exclusion
      criterion. The algorithm is integrated in the Lipid Data Analyzer (LDA)
      application which additionally provides standardization, a statistics module for
      results analysis, a batch mode for unattended analysis of several runs and a 3D
      viewer for the manual verification. The statistics module offers sample grouping,
      tests between sample groups and export functionalities, where the results are
      visualized by heat maps and bar charts. The presented algorithm has been applied
      to data from a controlled experiment and to biological data, containing analytes
      distributed over an intensity range of 10(6). Our approach shows improved
      sensitivity and an extremely high positive predictive value compared with
      existing methods. Consequently, the novel algorithm, integrated in a user
      friendly application, is a valuable improvement in the high-throughput analysis
      of the lipidome. IMPLEMENTATION AND AVAILABILITY: The Java application is freely
      available for non-commercial users at http://genome.tugraz.at/lda. Raw data
      associated with this manuscript may be downloaded from ProteomeCommons.org
      Tranche using the following hash:
      ZBh3nS5bXk6I/Vn32tB5Vh0qnMpVIW71HByFFQqM0RmdF4/4Hcn
      H3Wggh9kU2teYVOtM1JWwHIeMHqSS/bc2yYNFmyUAAAAAAACl DQ ==

PMID- 21169380
TI  - A novel method for assigning functional linkages to proteins using enhanced
      phylogenetic trees.
AB  - MOTIVATION: Functional linkages implicate pairwise relationships between proteins
      that work together to implement biological tasks. During evolution, functionally
      linked proteins are likely to be preserved or eliminated across a range of
      genomes in a correlated fashion. Based on this hypothesis, phylogenetic profiling
      based approaches try to detect pairs of protein families that show similar
      evolutionary patterns. Traditionally, the evolutionary pattern of a protein is
      encoded by either a binary profile of presence and absence of this protein across
      species or an occurrence profile that indicates the distribution of copies of
      this protein across species. RESULTS: In our study, we characterize each protein
      by its enhanced phylogenetic tree, a novel graphical model of the evolution of a
      protein family with explicitly marked by speciation and duplication events. By
      topological comparison between enhanced phylogenetic trees, we are able to detect
      the functionally associated protein pairs. Because the enhanced phylogenetic
      trees contain more evolutionary information of proteins, our method shows greater
      performance and discovers functional linkages among proteins more reliably
      compared with the conventional approaches.

PMID- 21169381
TI  - Low-molecular-mass of hyaluronan was detected in PASMCs from the patients with
      idiopathic pulmonary arterial hypertension.

PMID- 21169383
TI  - Requirement of the nuclear localization of transcription enhancer factor 3 for
      proliferation, migration, tube formation, and angiogenesis induced by vascular
      endothelial growth factor.
AB  - Transcription enhancer factor 3 (TEF3) is known to regulate the expression of
      muscle-specific genes and to play important roles in muscle development and
      diseases. However, little is known about its role in vascular endothelial growth
      factor (VEGF)-induced angiogenesis. Most recently, we discovered a novel function
      of TEF3, in which TEF3 is required for the up-regulation of a proangiogenic
      factor, Down syndrome candidate region 1 isoform 1L (DSCR1-1L), induced by VEGF
      A(165) in endothelial cells. Overexpression of TEF3 isoform 1 (TEF3-1) is
      sufficient to induce DSCR1-1L expression. Here, we report that knocking down the
      expression of TEF3 almost completely inhibits VEGF-A(165)-induced proliferation,
      migration, tube formation, formation of F-actin stress fiber, and in vivo
      Matrigel angiogenesis. This inhibition cannot be rescued by DSCR1-1L
      overexpression. Further, overexpression of TEF3-1, but not its nuclear
      localization signal-deletion mutant (TEF3-DeltaNLS), induces human umbilical vein
      endothelial cell proliferation, migration, tube formation, and formation of F
      actin stress fiber, even in the absence of VEGF-A(165) stimulation, which is
      partially inhibited by DSCR1-1L silencing. Our data demonstrate that TEF3, mainly
      its nuclear localization, is required for VEGF-A(165)-induced endothelial
      proliferation, migration, tube formation, and in vivo Matrigel angiogenesis.

PMID- 21169382
TI  - A constitutive pan-hexose permease for the Plasmodium life cycle and transgenic
      models for screening of antimalarial sugar analogs.
AB  - Glucose is considered essential for erythrocytic stages of the malaria parasite,
      Plasmodium falciparum. Importance of sugar and its permease for hepatic and
      sexual stages of Plasmodium, however, remains elusive. Moreover, increasing
      global resistance to current antimalarials necessitates the search for novel
      drugs. Here, we reveal that hexose transporter 1 (HT1) of Plasmodium berghei can
      transport glucose (K(m)~87 MUM), mannose (K(i)~93 MUM), fructose (K(i)~0.54 mM),
      and galactose (K(i)~5 mM) in Leishmania mexicana mutant and Xenopus laevis; and,
      therefore, is functionally equivalent to HT1 of P. falciparum (Glc, K(m)~175 MUM;
      Man, K(i)~276 MUM; Fru, K(i)~1.25 mM; Gal, K(i)~5.86 mM). Notably, a glucose
      analog, C3361, attenuated hepatic (IC(50)~15 MUM) and ookinete development of P.
      berghei. The PbHT1 could be ablated during intraerythrocytic stages only by
      concurrent complementation with PbHT1-HA or PfHT1. Together; these results
      signify that PbHT1 and glucose are required for the entire life cycle of P.
      berghei. Accordingly, PbHT1 is expressed in the plasma membrane during all
      parasite stages. To permit a high-throughput screening of PfHT1 inhibitors and
      their subsequent in vivo assessment, we have generated Saccharomyces cerevisiae
      mutant expressing codon-optimized PfHT1, and a PfHT1-dependent Deltapbht1
      parasite strain. This work provides a platform to facilitate the development of
      drugs against malaria, and it suggests a disease-control aspect by reducing
      parasite transmission.

PMID- 21169384
TI  - Functional genomics reveals diverse cellular processes that modulate tumor cell
      response to oxaliplatin.
AB  - Oxaliplatin is widely used to treat colorectal cancer, as both adjuvant therapy
      for resected disease and palliative treatment of metastatic disease. However, a
      significant number of patients experience serious side effects, including
      prolonged neurotoxicity, from oxaliplatin treatment creating an urgent need for
      biomarkers of oxaliplatin response or resistance to direct therapy to those most
      likely to benefit. As a first step to improve selection of patients for
      oxaliplatin-based chemotherapy, we have conducted an in vitro cell-based small
      interfering RNA (siRNA) screen of 500 genes aimed at identifying genes whose loss
      of expression alters tumor cell response to oxaliplatin. The siRNA screen
      identified twenty-seven genes, which when silenced, significantly altered colon
      tumor cell line sensitivity to oxaliplatin. Silencing of a group of putative
      resistance genes increased the extent of oxaliplatin-mediated DNA damage and
      inhibited cell-cycle progression in oxaliplatin-treated cells. The activity of
      several signaling nodes, including AKT1 and MEK1, was also altered. We used cDNA
      transfection to overexpress two genes (LTBR and TMEM30A) that were identified in
      the siRNA screen as mediators of oxaliplatin sensitivity. In both instances,
      overexpression conferred resistance to oxaliplatin. In summary, this study
      identified numerous putative predictive biomarkers of response to oxaliplatin
      that should be studied further in patient specimens for potential clinical
      application. Diverse gene networks seem to influence tumor survival in response
      to DNA damage by oxaliplatin. Finally, those genes whose loss of expression (or
      function) is related to oxaliplatin sensitivity may be promising therapeutic
      targets to increase patient response to oxaliplatin.

PMID- 21169386
TI  - Heart failure with preserved ejection fraction--a growing epidemic or 'The
      Emperor's New Clothes?'.

PMID- 21169385
TI  - Cardiovascular side effects of cancer therapies: a position statement from the
      Heart Failure Association of the European Society of Cardiology.
AB  - The reductions in mortality and morbidity being achieved among cancer patients
      with current therapies represent a major achievement. However, given their
      mechanisms of action, many anti-cancer agents may have significant potential for
      cardiovascular side effects, including the induction of heart failure. The
      magnitude of this problem remains unclear and is not readily apparent from
      current clinical trials of emerging targeted agents, which generally under
      represent older patients and those with significant co-morbidities. The risk of
      adverse events may also increase when novel agents, which frequently modulate
      survival pathways, are used in combination with each other or with other
      conventional cytotoxic chemotherapeutics. The extent to which survival and growth
      pathways in the tumour cell (which we seek to inhibit) coincide with those in
      cardiovascular cells (which we seek to preserve) is an open question but one that
      will become ever more important with the development of new cancer therapies that
      target intracellular signalling pathways. It remains unclear whether potential
      cardiovascular problems can be predicted from analyses of such basic signalling
      mechanisms and what pre-clinical evaluation should be undertaken. The screening
      of patients, optimization of therapeutic schemes, monitoring of cardiovascular
      function during treatment, and the management of cardiovascular side effects are
      likely to become increasingly important in cancer patients. This paper summarizes
      the deliberations of a cross-disciplinary workshop organized by the Heart Failure
      Association of the European Society of Cardiology (held in Brussels in May 2009),
      which brought together clinicians working in cardiology and oncology and those
      involved in basic, translational, and pharmaceutical science.

PMID- 21169387
TI  - Direct renin inhibition in addition to or as an alternative to angiotensin
      converting enzyme inhibition in patients with chronic systolic heart failure:
      rationale and design of the Aliskiren Trial to Minimize OutcomeS in Patients with
      HEart failuRE (ATMOSPHERE) study.
AB  - AIMS: The renin-angiotensin-aldosterone system (RAAS) represents a key
      therapeutic target in heart failure (HF) management. However, conventional agents
      that block this system induce a reflex increase in plasma renin activity (PRA),
      which may lead to RAAS 'escape'. Direct renin inhibitors (DRIs) have been
      developed that decrease PRA and thus may provide a greater RAAS blockade.
      Aliskiren is the first orally active DRI. Plasma levels of B-type natriuretic
      peptide (BNP) have been observed to be reduced with aliskiren compared with
      placebo. The aim of the Aliskiren Trial of Minimizing OutcomeS for Patients with
      HEart failuRE (ATMOSPHERE) study is to evaluate the effect of both aliskiren and
      enalapril monotherapy and aliskiren/enalapril combination therapy on
      cardiovascular death and HF hospitalization in patients with chronic systolic HF,
      NYHA functional class II-IV symptoms, and elevated plasma levels of BNP. Methods
      Patients tolerant to at least 10 mg or equivalent of enalapril will undergo an
      open-label run-in period where they receive enalapril then aliskiren.
      Approximately 7000 patients tolerating this run-in period will then be randomized
      1:1:1 to aliskiren monotherapy, enalapril monotherapy, or the combination. The
      primary endpoints of ATMOSPHERE are (i) whether the aliskiren/enalapril
      combination is superior to enalapril monotherapy in delaying time to first
      occurrence of cardiovascular death or HF hospitalization and (ii) whether
      aliskiren monotherapy is superior or at least non-inferior to enalapril
      monotherapy on this endpoint. Perspective The ATMOSPHERE study will definitively
      determine the role of a DRI strategy additional to or as an alternative to
      conventional RAAS blockade in patients with chronic systolic HF.

PMID- 21169388
TI  - Nicotine reverses anhedonic-like response and cognitive impairment in the rat
      chronic mild stress model of depression: comparison with sertraline.
AB  - Smoking rates among depressed individuals are higher than is observed in the
      background population, and nicotine alleviates depressive symptoms. In rodents,
      nicotine shows antidepressant-like effects in the forced swim and learned
      helplessness paradigms. Clinical depression is associated with both anhedonia and
      cognitive impairments. In rats, chronic mild stress (CMS) decreases voluntary
      sucrose intake, reflecting an anhedonic-like state, and impairs performance in
      the spontaneous alternation behaviour (SAB) test, suggesting impaired cognitive
      function. Here, we examine the effect of chronic treatment of nicotine (0.4
      mg/kg/day) and sertraline (5 mg/kg/day) on CMS-induced anhedonic-like behaviour
      and impairment in the SAB test. Nicotine and sertraline administered individually
      or in combination show significant and equally efficacious reversal of the CMS
      induced decrease in sucrose intake, implying there is no additive or synergistic
      effect of the nicotine + sertraline combination. In the SAB test, nicotine, but
      not sertraline or nicotine + sertraline, reversed the CMS-induced impairment. The
      present results show that the effect of nicotine on a CMS-induced anhedonic-like
      state in rats is similar to that of a standard antidepressant drug. Moreover, the
      data suggest that nicotine alleviates CMS-induced cognitive disturbance. A
      treatment strategy involving the targeting of nicotinic acetylcholine receptors
      may prove beneficial for emotional and cognitive disturbances associated with
      depression.

PMID- 21169389
TI  - Hyperhomocysteinemia does not affect global DNA methylation and nicotinamide N
      methyltransferase expression in mice.
AB  - DNA methylation is coupled with one-carbon metabolism involving
      homocysteine/methionine interconversion. Correlation between plasma homocysteine
      levels and leukocyte global DNA methylation was reported but not always
      replicated. Nicotinamide N-methyltransferase (NNMT) is a determinant of plasma
      homocysteine levels. Findings suggest alteration of one-carbon metabolism in
      schizophrenia etiology; hyperhomocysteinemia was observed in schizophrenia. A
      recent study carried out by the authors of this paper found an association
      between NNMT and schizophrenia and decreased post-mortem brain NNMT mRNA levels.
      The present study assessed the interrelationship between brain and leukocytes
      global DNA methylation and plasma homocysteine levels, and between
      hyperhomocysteinemia and brain NNMT expression. Mice were administered
      homocysteine in drinking water. Percentage global genome DNA methylation was
      measured using the cytosine-extension method, and NNMT expression was measured
      using real-time quantitative reverse transcriptase PCR (qRT-PCR). Homocysteine
      administration resulted in a 10-fold increase in plasma homocysteine. However,
      there was no change in global DNA methylation in lymphocytes or in the frontal
      cortex. No significant intra-individual correlation was found between global DNA
      methylation in leukocytes and frontal cortex, suggesting that leukocyte global
      DNA methylation may not serve as a marker for brain global DNA methylation. No
      difference was found in NNMT expression in homocysteine-treated mice compared
      with control mice. In conclusion, relatively short-term hyperhomocysteinemia in
      mice does not reproduce or lead to alterations reported in one-carbon metabolism
      in disorders associated with lifelong elevated plasma homocysteine.

PMID- 21169390
TI  - Metformin for obesity and glucose dysregulation in patients with schizophrenia
      receiving antipsychotic drugs.
AB  - Antipsychotic drug-induced weight gain and glucose dysregulation add to the
      cardiovascular risk of patients with schizophrenia and contribute to their early
      mortality. The currently recommended interventions to address the metabolic
      complications of antipsychotic drug treatment are to switch the patient from an
      antipsychotic drug with high metabolic liability to one with a lower liability
      and to implement lifestyle changes. These interventions can be quite challenging
      to carry out. So far the progress in improving the metabolic and cardiovascular
      outcome of patients with major mental illness has been disappointing. We offer an
      overview of the literature on metformin for antipsychotic drug-induced weight
      gain and glucose dysregulation and pertinent literature from the Diabetes
      Prevention Program. We conclude that young adults with schizophrenia newly
      exposed to antipsychotic drugs, who show a pattern of rapid weight gain and/or
      glucose dysregulation, are prime candidates for metformin if switching the
      antipsychotic medication to one with a lower metabolic burden is not an option or
      does not curtail the weight gain and/or adverse metabolic effects. Metformin
      therapy should not preclude healthy lifestyle interventions.

PMID- 21169391
TI  - Experimental medicine in drug addiction: towards behavioral, cognitive and
      neurobiological biomarkers.
AB  - Several theoretical frameworks have been developed to understand putative
      processes and mechanisms involved in addiction. Whilst these 'theories of
      addiction' disagree about importance and/or nature of a number of key
      psychological processes (e.g. the necessity of craving and/or the involvement of
      drug-value representations), a number of commonalities exist. For instance, it is
      widely accepted that Pavlovian associations between cues and environmental
      contexts and the drug effects acquired over the course of addiction play a
      critical role, especially in relapse vulnerability in detoxified addicts.
      Additionally, all theories of addiction (explicitly or implicitly) propose that
      chronic drug exposure produces persistent neuroplastic changes in neurobiological
      circuitries underlying critical emotional, cognitive and motivational processes,
      although disagreement exists as to the precise nature of these neurobiological
      changes and/or their psychological consequences. The present review, rather than
      limiting itself to any particular theoretical stance, considers various candidate
      psychological, neurobiological and/or behavioral processes in addiction and
      outlines conceptual and procedural approaches for the experimental medicine
      laboratory. The review discusses (1) extinction, renewal and (re)consolidation of
      learned associations between cues and drugs, (2) the drug reward value, (3)
      motivational states contributing to drug seeking and (4) reflective (top-down)
      and sensory (bottom-up) driven decision-making. In evaluating these psychological
      and/or behavioral processes and their relationship to addiction we make reference
      to putative underlying brain structures identified by basic animal studies and/or
      imaging studies with humans.

PMID- 21169393
TI  - The role of nucleus accumbens shell GABA receptors on ventral tegmental area
      intracranial self-stimulation and a potential role for the 5-HT(2C) receptor.
AB  - Brain gamma-aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT)(2C) receptors
      are implicated in the neuronal regulation of reward- and aversion-related
      behaviour. Within the mesocorticolimbic pathways of the brain, relationships
      between GABA containing neurons and 5-HT(2C) receptor activity may be important
      in this context. The primary aim of this study was to investigate the role of NAc
      shell GABA receptors on ventral tegmental area intracranial self-stimulation
      (ICSS) and to examine the systemic effects of GABAergic ligands in this context.
      The second aim was to investigate the relationship between GABA receptor- and 5
      HT(2C) receptor-related ICSS behaviour, using systemic administration of the
      selective agonist WAY 161503. Locomotor activity was assessed to compare the
      potential motor effects of drugs; feeding behaviour and intra-NAc injections of
      amphetamine (1.0 ug/side) were used as positive controls. When administered
      systemically the GABA(A) receptor agonist muscimol and antagonist picrotoxin did
      not selectively change ICSS reward thresholds, although the 5-HT(2C) receptor
      agonist WAY 161503 (1.0 mg/kg) decreased reward measures. Intra-NAc shell
      administration of muscimol (225 ng/side) and picrotoxin (125 ng/side),
      respectively, decreased and increased measures of reward. Intra-NAc shell
      baclofen (0-225 ng/side; GABA(B) receptor agonist) did not affect any ICSS
      measures although it increased feeding. Combining picrotoxin and WAY 161503
      attenuated the effects of each. These results suggest that a 5-HT(2C) and GABA(A)
      receptor-mediated neuronal relationship in the NAc shell may be relevant for the
      regulation of brain reward pathways.

PMID- 21169392
TI  - Examining antidepressant drug response by smoking status: why is it important and
      how often is it done?
AB  - Despite an increasingly recognized relationship between depression and smoking,
      little is known about the degree to which treatment studies for depression
      consider the impact of smoking on outcomes. The aim of this study is to examine
      the extent to which smoking is considered in current antidepressant treatment
      research. We conducted a MEDLINE search of recent randomized clinical trials of
      pharmacotherapy for depression published between 1 January and 31 December 2007,
      and a search of current pharmacological intervention studies for depression using
      www.ClinicalTrials.gov. Only 5% of the 107 pharmacological trials for depression
      published in 2007 reported the smoking status of their samples. Two studies
      (1.9%) controlled for smoking in the analyses and no studies analyzed outcomes by
      smoking status. Excluding the eight studies of combined treatment for depression
      and nicotine dependence, no other study on www.ClinicalTrials.gov (total n = 920)
      reported an intention to analyze outcomes by smoking status. Emerging data link
      smoking and depression, however, little attention has been directed toward the
      effects of smoking on antidepressant treatment outcomes. Conducting research to
      understand how nicotine and smoking affect responsiveness to antidepressants
      would advance our understanding of the neurobiology of depression and the
      development of new and targeted treatments.

PMID- 21169394
TI  - Effects of dieting status and cigarette deprivation on progressive ratio
      responding for cigarette puffs by young women smokers.
AB  - There is evidence from self-report measures which suggests that young women
      dieters find cigarette smoking less rewarding than non-dieters. We aimed to
      further elucidate differences between dieters and non-dieters in their evaluation
      of smoking using a behavioural measure of drug reward. Thirty female
      undergraduates attended two sessions (cigarette deprived and non-deprived). A
      computer-based progressive ratio operant procedure was employed to assess the
      amount of effort that participants were willing to expend to gain a puff on a
      cigarette. The point at which responding ceased was taken as a measure of drug
      reward (breakpoint). Self-report measures of sensory/hedonic aspects of smoking
      were also completed. The breakpoints of both dieters and non-dieters were greater
      under deprived than non-deprived conditions but the breakpoints of dieters were
      significantly lower than those of the non-dieting smokers under both conditions.
      Self-reported enjoyment of smoking was lower for dieters than non-dieters and
      reports for non-dieters but not dieters were affected by deprivation level. Both
      behavioural and self-report measures of rewarding aspects of smoking suggest that
      young women dieters find smoking less rewarding than non-dieters, but self-report
      measures are more resistant to deprivation effects for dieters. This is
      consistent with the suggestion that subjective and behavioural measures assess
      different dimensions of the rewarding effects of smoking.

PMID- 21169395
TI  - Detection of specific glycosaminoglycans and glycan epitopes by in vitro
      sulfation using recombinant sulfotransferases.
AB  - Sulfated glycans play critical roles during the development, differentiation and
      growth of various organisms. The most well-studied sulfated molecules are
      sulfated glycosaminoglycans (GAGs). Recent incidents of heparin drug
      contamination convey the importance of having a convenient and sensitive method
      for detecting different GAGs. Here, we describe a molecular method to detect GAGs
      in biological and biomedical samples. Because the sulfation of GAGs is generally
      not saturated in vivo, it is possible to introduce the radioisotope (35)S in
      vitro using recombinant sulfotransferases, thereby allowing detection of minute
      quantities of these molecules. This strategy was also successfully applied in the
      detection of other glycans. As examples, we detected contaminant GAGs in
      commercial heparin, heparan sulfate and chondroitin samples. The identities of
      the contaminant GAGs were further confirmed by lyase digestion. Oversulfated
      chondroitin sulfate was detectable only following a simple desulfation step.
      Additionally, in vitro sulfation by sulfotransferases allowed us to map glycan
      epitopes in biological samples. This was illustrated using mouse embryo and rat
      organ tissue sections labeled with the following carbohydrate sulfotransferases:
      CHST3, CHST15, HS3ST1, CHST4 and CHST10.

PMID- 21169396
TI  - Endothelial inflammation correlates with subject triglycerides and waist size
      after a high-fat meal.
AB  - A rise in postprandial serum triglycerides (PP-sTG) can potentiate inflammatory
      responses in vascular endothelial cells (ECs) and thus serves as an independent
      risk factor for predicting increased cardiovascular morbidity. We examined
      postprandial triglyceride-rich lipoproteins (PP-TGRLs) in subjects ranging from
      normal to hypertriglyceridemic for their capacity to alter EC acute inflammatory
      responses. Cultured human aortic ECs (HAECs) were conditioned with PP-TGRLs
      isolated from human serum at the peak after a moderately high-fat meal. VLDL
      particle size increased postprandially and varied directly with the subject's PP
      sTG level and waist circumference. PP-TGRL particles bound to HAECs and were
      internalized via LDL receptor-mediated endocytosis. PP-TGRL alone did not induce
      an inflammatory response over the range of individuals studied. However, combined
      with low-dose TNF-alpha stimulation (0.3 ng/ml), it elicited a net 10-15%
      increase above cytokine alone in the membrane expression of VCAM-1, ICAM-1, and E
      selectin, which was not observed with fasting TGRLs. In contrast to upregulation
      of ICAM-1 and E-selectin, VCAM-1 transcription and expression varied in direct
      proportion with individual PP-sTG and waist circumference. The extent of monocyte
      arrest on inflamed HAECs under shear stress also correlated closely with VCAM-1
      expression induced by conditioning with PP-TGRL and TNF-alpha stimulation. This
      ex vivo approach provides a quantitative means to assess an individual's
      inflammatory potential, revealing a greater propensity for endothelial
      inflammation in hypertriglyceridemic individuals with abdominal obesity.

PMID- 21169397
TI  - The role of mitosis in LDL transport through cultured endothelial cell
      monolayers.
AB  - We (7) have previously shown that leaky junctions associated with dying or
      dividing cells are the dominant pathway for LDL transport under convective
      conditions, accounting for >90% of the transport. We (8) have also recently shown
      that the permeability of bovine aortic endothelial cell monolayers is highly
      correlated with their rate of apoptosis and that inhibiting apoptosis lowers the
      permeability of the monolayers to LDL. To explore the role of mitosis in the
      leaky junction pathway, the microtubule-stabilizing agent paclitaxel was used to
      alter the rate of mitosis, and LDL flux and water flux (J(v)) were measured.
      Control monolayers had an average mitosis rate of 0.029%. Treatment with
      paclitaxel (2.5 MUM) for 1.5, 3, 4.5, or 6 h yielded increasing rates of mitosis
      ranging from 0.099% to 1.03%. The convective permeability of LDL (P(e)) increased
      up to fivefold, whereas J(v) increased up to threefold, over this range of
      mitosis rates. We found strong correlations between the mitosis rate and both
      P(e) and J(v). However, compared with our previous apoptosis study (8), we found
      that mitosis was only half as effective as apoptosis in increasing P(e). The
      results led us to conclude that while mitosis-related leaky junctions might play
      a role in the initial infiltration of LDL into the artery wall, the progression
      of atherosclerosis might be more closely correlated with apoptosis-related leaky
      junctions.

PMID- 21169398
TI  - Why is the subendocardium more vulnerable to ischemia? A new paradigm.
AB  - Myocardial ischemia is transmurally heterogeneous where the subendocardium is at
      higher risk. Stenosis induces reduced perfusion pressure, blood flow
      redistribution away from the subendocardium, and consequent subendocardial
      vulnerability. We propose that the flow redistribution stems from the higher
      compliance of the subendocardial vasculature. This new paradigm was tested using
      network flow simulation based on measured coronary anatomy, vessel flow and
      mechanics, and myocardium-vessel interactions. Flow redistribution was quantified
      by the relative change in the subendocardial-to-subepicardial perfusion ratio
      under a 60-mmHg perfusion pressure reduction. Myocardial contraction was found to
      induce the following: 1) more compressive loading and subsequent lower
      transvascular pressure in deeper vessels, 2) consequent higher compliance of the
      subendocardial vasculature, and 3) substantial flow redistribution, i.e., a 20%
      drop in the subendocardial-to-subepicardial flow ratio under the prescribed
      reduction in perfusion pressure. This flow redistribution was found to occur
      primarily because the vessel compliance is nonlinear (pressure dependent). The
      observed thinner subendocardial vessel walls were predicted to induce a higher
      compliance of the subendocardial vasculature and greater flow redistribution.
      Subendocardial perfusion was predicted to improve with a reduction of either
      heart rate or left ventricular pressure under low perfusion pressure. In
      conclusion, subendocardial vulnerability to a acute reduction in perfusion
      pressure stems primarily from differences in vascular compliance induced by
      transmural differences in both extravascular loading and vessel wall thickness.
      Subendocardial ischemia can be improved by a reduction of heart rate and left
      ventricular pressure.

PMID- 21169399
TI  - Left ventricular systolic torsion correlates global cardiac performance during
      dyssynchrony and cardiac resynchronization therapy.
AB  - Left ventricular (LV) systolic torsion is a primary mechanism contributing to
      stroke volume (SV). We hypothesized that change in LV torsion parallels changes
      in global systolic performance during dyssynchrony and cardiac resynchronization
      therapy (CRT). Seven anesthetized open chest dogs had LV pressure-volume
      relationship. Apical, basal, and mid-LV cross-sectional echocardiographic images
      were studied by speckle tracking analysis. Right atrial (RA) pacing served as
      control. Right ventricular (RV) pacing simulated left bundle branch block.
      Simultaneous RV-LV free wall and RV-LV apex pacing (CRTfw and CRTa, respectively)
      modeled CRT. Dyssynchrony was defined as the time difference in peak strain
      between earliest and latest segments. Torsion was calculated as the maximum
      difference between the apical and basal rotation. RA pacing had minimal
      dyssynchrony (52 +/- 36 ms). RV pacing induced dyssynchrony (189 +/- 61 ms, P <
      0.05). CRTa decreased dyssynchrony (46 +/- 36 ms, P < 0.05 vs. RV pacing),
      whereas CRTfw did not (110 +/- 96 ms). Torsion during baseline RA was 6.6 +/- 3.7
      degrees . RV pacing decreased torsion (5.1 +/- 3.6 degrees , P < 0.05 vs.
      control), and reduced SV, stroke work (SW), and dP/dt(max) compared with RA (21
      +/- 5 vs. 17 +/- 5 ml, 252 +/- 61 vs. 151 +/- 64 mJ, and 2,063 +/- 456 vs. 1,603
      +/- 424 mmHg/s, respectively, P < 0.05). CRTa improved torsion, SV, SW, and
      dP/dt(max) compared with RV pacing (7.7 +/- 4.7 degrees , 23 +/- 3 ml, 240 +/- 50
      mJ, and 1,947 +/- 647 mmHg/s, respectively, P < 0.05), whereas CRTfw did not (5.1
      +/- 3.6 degrees , 18 +/- 5 ml, 175 +/- 48 mJ, and 1,699 +/- 432 mmHg/s,
      respectively, P < 0.05). LV torsion changes covaried across conditions with SW (y
      = 0.94x+12.27, r = 0.81, P < 0.0001) and SV (y = 0.66x+0.91, r = 0.81, P <
      0.0001). LV dyssynchrony changes did not correlate with SW or SV (r = -0.12, P =
      0.61 and r = 0.08, P = 0.73, respectively). Thus, we conclude that LV torsion is
      primarily altered by dyssynchrony, and CRT that restores LV performance also
      restores torsion.

PMID- 21169400
TI  - Platelets enhance neutrophil transendothelial migration via P-selectin
      glycoprotein ligand-1.
AB  - Platelets are increasingly recognized as important for inflammation in addition
      to thrombosis. Platelets promote the adhesion of neutrophils [polymorphonuclear
      neutrophils (PMNs)] to the endothelium; P-selectin and P-selectin glycoprotein
      ligand (PSGL)-1 have been suggested to participate in these interactions. Whether
      platelets also promote PMN transmigration across the endothelium is less clear.
      We tested the hypothesis that platelets enhance PMN transmigration across the
      inflamed endothelium and that PSGL-1 is involved. We studied the effects of
      platelets on PMN transmigration in vivo and in vitro using a well-characterized
      corneal injury model in C57BL/6 mice and IL-1beta-stimulated human umbilical vein
      endothelial cells (HUVECs) under static and dynamic conditions. In vivo, platelet
      depletion altered PMN emigration from limbal microvessels after injury, with
      decreased emigration 6 and 12 h after injury. Both PSGL-1-/- and P-selectin-/-
      mice, but not Mac-1-/- mice, also had reduced PMN emigration at 12 h after injury
      relative to wild-type control mice. In the in vitro HUVEC model, platelets
      enhanced PMN transendothelial migration under static and dynamic conditions
      independent of firm adhesion. Anti-PSGL-1 antibodies markedly inhibited platelet
      PMN aggregates, as assessed by flow cytometry, and attenuated the effect of
      platelets on PMN transmigration under static conditions without affecting firm
      adhesion. These data support the notion that platelets enhance neutrophil
      transmigration across the inflamed endothelium both in vivo and in vitro, via a
      PSGL-1-dependent mechanism.

PMID- 21169402
TI  - Functional medial thickening and folding of the internal elastic lamina in
      coronary spasm.
AB  - Although there are a number of studies on vasospastic angina, the structural
      changes at the cellular level that occur in the coronary arterial wall during
      spasm are not well known. Coronary spasm was induced by brushing the coronary
      adventitia in nine anesthetized beagles, and structural changes in the spastic
      coronary segments were examined by light and electron microscopy, making
      comparisons with the adjacent nonspastic segments. The % diameter stenosis of the
      spastic segments as measured angiographically was 79.4+/-12% (mean+/-SD). Light
      microscopic changes in the spastic and nonspastic segments were as follows:
      medial thickness 1,512 vs. 392 MUm (P<0.0001) and % diameter and % area stenoses
      of spastic segment 81.0% and 96.5%, respectively, indicating that spasm was
      induced by medial thickening. Circular smooth muscle cells (SMCs) in the media
      were arranged in parallel with the internal (IEL) and external (EEL) elastic
      lamina in nonspastic segments but radially rearranged in spastic segments. SMCs
      were classified by their patterns of connection to IEL into six types by electron
      microscopy. Of these, three contracted and pulled the IEL toward the EEL, causing
      folding of the IEL and waving of EEL resulting in thickening of the media and
      narrowing of the lumen. We conclude that coronary spasm was elicited by radial
      rearrangement of the medial SMCs due to their own contraction and resultant
      medial thickening and folding of IEL, creating a piston effect to narrow the
      lumen, i.e., spasm.

PMID- 21169401
TI  - Cyclic stretch stimulates vascular smooth muscle cell alignment by redox
      dependent activation of Notch3.
AB  - Mice deficient in Notch3 have defects in arterial vascular smooth muscle cell
      (VSMC) mechanosensitivity, including impaired myogenic responses and
      autoregulation, and inappropriate VMSC orientation. Experiments were performed to
      determine if Notch3 is activated by mechanical stimulation and contributes to
      mechanosensitive responses of VSMCs, including cell realignment. Cyclic, uniaxial
      stretch (10%, 1 Hz) of human VSMCs caused Notch3 activation, demonstrated by a
      stretch-induced increase in hairy and enhancer of split 1/hairy-related
      transcription factor-1 expression, translocation of Notch3 to the nucleus, and a
      decrease in the Notch3 extracellular domain. These effects were prevented by
      inhibiting the expression [small interfering (si)RNA] or proteolytic activation
      of Notch3 {N-(R)-[2-(hydroxyaminocarbonyl)methyl]-4-methylpentanoyl-l
      naphthylalanyl-l-alanine-2-aminoethyl amide (TAPI-1; 50 MUmol/l) to inhibit TNF
      alpha-converting enzyme (TACE) or N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S
      phenylglycine t-butyl ester (DAPT; 20 MUmol/l) to inhibit gamma-secretase}.
      Stretch increased the activity of ROS within VSMCs, determined using
      dichlorodihydrofluorescein fluorescence. Catalase (1,200 U/ml), which degrades
      H2O2, inhibited the stretch-induced activation of Notch3, whereas in nonstretched
      cells, increasing H2O2 activity [H2O2 or manganese(III) tetrakis(1-methyl-4
      pyridyl)porphyrin] caused activation of Notch3. Stretch increased the activity of
      TACE, which was prevented by catalase. Stretch-induced activation of p38 MAPK in
      VSMCs was inhibited either by catalase or by inhibiting Notch3 expression
      (siRNA). Stretch caused VSMCs to realign perpendicular to the direction of the
      mechanical stimulus, which was significantly inhibited by catalase or by
      inhibiting the expression (siRNA) or activation of Notch3 (TAPI-1 or DAPT).
      Therefore, cyclic uniaxial stretch activates Notch3 signaling through a ROS
      mediated mechanism, and the presence of Notch3 is necessary for proper stretch
      induced cell alignment in VSMCs. This mechanism may contribute to the
      physiological role of Notch3 in mediating developmental maturation of VSMCs.

PMID- 21169404
TI  - Mthfr deficiency induces endothelial progenitor cell senescence via uncoupling of
      eNOS and downregulation of SIRT1.
AB  - Hyperhomocysteinemia (HHcy) has been shown to induce endothelial dysfunction in
      part as a result of enhanced oxidative stress. Function and survival of
      endothelial progenitor cells (EPCs, defined as sca1(+) c-kit(+) flk-1(+) bone
      marrow-derived cells), which significantly contribute to neovascularization and
      endothelial regeneration, depend on controlled production of reactive oxygen
      species (ROS). Mice heterozygous for the gene deletion of
      methylenetetrahydrofolate reductase (Mthfr(+/-)) have a 1.5- to 2-fold elevation
      in plasma homocysteine. This mild HHcy significantly reduced the number of
      circulating EPCs as well as their differentiation. Mthfr deficiency was also
      associated with increased ROS production and reduced nitric oxide (NO) generation
      in Mthfr(+/-) EPCs. Treatment of EPCs with sepiapterin, a precursor of
      tetrahydrobiopterin (BH(4)), a cofactor of endothelial nitric oxide synthase
      (eNOS), significantly reduced ROS and improved NO production. mRNA and protein
      expression of eNOS and the relative amount of eNOS dimer compared with monomer
      were decreased by Mthfr deficiency. Impaired differentiation of EPCs induced by
      Mthfr deficiency correlated with increased senescence, decreased telomere length,
      and reduced expression of SIRT1. Addition of sepiapterin maintained cell
      senescence and SIRT1 expression at levels comparable to the wild type. Taken
      together, these results demonstrate that Mthfr deficiency impairs EPC formation
      and increases EPC senescence by eNOS uncoupling and downregulation of SIRT1.

PMID- 21169405
TI  - NKX2.2 suppresses self-renewal of glioma-initiating cells.
AB  - Glioblastoma (GBM) is the most aggressive and destructive form of brain cancer.
      Animal models that can unravel the mechanisms underlying its progression are
      needed to develop rational and effective molecular therapeutic approaches. In
      this study, we report the development of mouse models for spontaneous gliomas
      representing distinct progressive stages of disease that are governed by defined
      genetic alterations. Neural stem/progenitor cell (NPC)-specific constitutive Ras
      activation in vivo plus p53 deficiency led to development of primarily anaplastic
      astrocytoma (grade III), whereas combined loss of p53 plus p16(Ink4a)/p19(Arf)
      led to development of GBM (grade IV) at 100% penetrance within 6 weeks. These
      glioma models showed enhanced stem cell properties (stemness) accompanied by
      malignant progression. Notably, we determined that, in our models and in human
      specimens, downregulation of the homeodomain transcription factor NKX2.2, which
      is essential for oligodendroglial differentiation, was correlated with increased
      tumor malignancy. NKX2.2 overexpression by GBM-derived glioma-initiating cells
      (GIC) induced oligodendroglial differentiation and suppressed self-renewal
      capacity. By contrast, Nkx2.2 downregulation in mouse NPCs accelerated GBM
      formation. Importantly, the inhibitory effects of NXK2.2 on GIC self-renewal were
      conserved in human cells. Thus, our mouse models offer pathobiologically
      significant advantages to investigate the nature of brain tumors, with improved
      opportunities to develop novel mechanism-based therapeutic approaches.

PMID- 21169403
TI  - Exercise training normalizes impaired NOS-dependent responses of cerebral
      arterioles in type 1 diabetic rats.
AB  - Our goal was to examine whether exercise training (ExT) could normalize impaired
      nitric oxide synthase (NOS)-dependent dilation of cerebral (pial) arterioles
      during type 1 diabetes (T1D). We measured the in vivo diameter of pial arterioles
      in sedentary and exercised nondiabetic and diabetic rats in response to an
      endothelial NOS (eNOS)-dependent (ADP), an neuronal NOS (nNOS)-dependent [N
      methyl-D-aspartate (NMDA)], and a NOS-independent (nitroglycerin) agonist. In
      addition, we measured superoxide anion levels in brain tissue under basal
      conditions in sedentary and exercised nondiabetic and diabetic rats. Furthermore,
      we used Western blot analysis to determine eNOS and nNOS protein levels in
      cerebral vessels/brain tissue in sedentary and exercised nondiabetic and diabetic
      rats. We found that ADP and NMDA produced a dilation of pial arterioles that was
      similar in sedentary and exercised nondiabetic rats. In contrast, ADP and NMDA
      produced only minimal vasodilation in sedentary diabetic rats. ExT restored
      impaired ADP- and NMDA-induced vasodilation observed in diabetic rats to that
      observed in nondiabetics. Nitroglycerin produced a dilation of pial arterioles
      that was similar in sedentary and exercised nondiabetic and diabetic rats.
      Superoxide levels in cortex tissue were similar in sedentary and exercised
      nondiabetic rats, were increased in sedentary diabetic rats, and were normalized
      by ExT in diabetic rats. Finally, we found that eNOS protein was increased in
      diabetic rats and further increased by ExT and that nNOS protein was not
      influenced by T1D but was increased by ExT. We conclude that ExT can alleviate
      impaired eNOS- and nNOS-dependent responses of pial arterioles during T1D.

PMID- 21169406
TI  - A mammaglobin-A targeting agent for noninvasive detection of breast cancer
      metastasis in lymph nodes.
AB  - Pathologic axillary lymph node (ALN) status is an important prognostic factor for
      staging breast cancer. Currently, status is determined by histopathology
      following surgical excision of sentinel lymph node(s), which is an invasive, time
      consuming, and costly procedure with potential morbidity to the patient. Here, we
      describe an imaging platform for noninvasive assessment of ALN status,
      eliminating the need for surgical examination of patients to rule out nodal
      involvement. A targeted imaging probe (MamAb-680) was developed by conjugation of
      a mammaglobin-A-specific monoclonal antibody to a near-infrared fluorescent dye.
      Using DNA and tissue microarray, mammaglobin-A was validated as a cell-surface
      target that is expressed in ALN-positive patient samples but is not expressed in
      normal lymph nodes. In vivo selectivity was determined by i.v. injection of MamAb
      680 into mice with mammaglobin-A-positive and -negative mammary fat pad (MFP)
      tumors; and by peritumoral MFP injection of the targeted imaging probe in mice
      with spontaneous ALN metastases. Fluorescence imaging showed that probe was only
      retained in positive tumors and metastases. As few as 1,000 cells that
      endogenously express mammaglobin-A were detected in ALN, indicating high
      sensitivity of this method. Translation of this approach offers considerable
      potential as a noninvasive clinical strategy to stage breast cancer.

PMID- 21169407
TI  - Using a stem cell-based signature to guide therapeutic selection in cancer.
AB  - Given the very substantial heterogeneity of most human cancers, it is likely that
      most cancer therapeutics will be active in only a small fraction of any
      population of patients. As such, the development of new therapeutics, coupled
      with methods to match a therapy with the individual patient, will be critical to
      achieving significant gains in disease outcome. One such opportunity is the use
      of expression signatures to identify key oncogenic phenotypes that can serve not
      only as biomarkers but also as a means of identifying therapeutic compounds that
      might specifically target these phenotypes. Given the potential importance of
      targeting tumors exhibiting a stem-like phenotype, we have developed an
      expression signature that reflects common biological aspects of various stem-like
      characteristics. The consensus stemness ranking (CSR) signature is upregulated in
      cancer stem cell-enriched samples at advanced tumor stages and is associated with
      poor prognosis in multiple cancer types. Using two independent computational
      approaches we utilized the CSR signature to identify clinically useful compounds
      that could target the CSR phenotype. In vitro assays confirmed selectivity of
      several predicted compounds including topoisomerase inhibitors and resveratrol
      towards breast cancer cell lines that exhibit a high-CSR phenotype. Importantly,
      the CSR signature could predict clinical response of breast cancer patients to a
      neoadjuvant regimen that included a CSR-specific agent. Collectively, these
      results suggest therapeutic opportunities to target the CSR phenotype in a
      relevant cohort of cancer patients.

PMID- 21169408
TI  - Recovery of anoikis in Src-transformed cells and human breast carcinoma cells by
      restoration of the SIRP alpha1/SHP-2 signaling system.
AB  - Src kinase dysregulation contributes to cancer progression but mechanistic
      understanding for this contribution remains incomplete. Signal regulatory protein
      alpha1 (SIRPalpha1) is a tumor suppressor that is constitutively suppressed in v
      Src-transformed cells, where restoration of SIRPalpha1 expression inhibits
      anchorage-independent growth. In this study, we investigated the role of the
      protein tyrosine phosphatase-2 (SHP-2) in SIRPalpha1 activity. SHP-2 suppression
      resulted in a blockade of SIRPalpha1-mediated inhibition of anchorage-independent
      growth. Notably, we found that SIRPalpha1 did not act in v-Src-transformed cells
      by triggering cell growth arrest but by eliciting a suspension-selective
      apoptosis (anoikis), and that SHP-2 was required for this effect. Furthermore, we
      found that SHP-2 was crucial for recovery of stress fiber and focal contact
      formation by SIRPalpha1 in v-Src-transformed cells. Finally, we found that
      SIRPalpha1/SHP-2 signaling regulates anoikis in human breast carcinoma cells with
      activated c-Src. Taken together, our findings define SHP-2 as an essential
      component of tumor suppression and anoikis mediated by SIRPalpha1 in human breast
      carcinoma cells as well as in v-Src-transformed cells.

PMID- 21169409
TI  - The epithelial-mesenchymal transition mediator S100A4 maintains cancer-initiating
      cells in head and neck cancers.
AB  - Cancer-initiating cells (CIC) comprise a rare subpopulation of cells in tumors
      that are proposed to be responsible for tumor growth. Starting from CICs
      identified in head and neck squamous cell carcinomas (HNSCC), termed head and
      neck cancer-initiating cells (HN-CIC), we determined as a candidate stemness
      maintaining molecule for HN-CICs the proinflammatory mediator S100A4, which is
      also known to be an inducer of epithelial-mesenchymal transition. S100A4
      knockdown in HN-CICs reduced their self-renewal capability and their stemness and
      tumorigenic properties, both in vitro and in vivo. Conversely, S100A4
      overexpression in HNSCC cells enhanced their stem cell properties. Mechanistic
      investigations indicated that attenuation of endogenous S100A4 levels in HNSCC
      cells caused downregulation of Notch2 and PI3K (phosphoinositide 3-kinase)/pAKT
      along with upregulation of PTEN, consistent with biological findings.
      Immunohistochemical analysis of HNSCC clinical specimens showed that S100A4
      expression was positively correlated with clinical grading, stemness markers, and
      poorer patient survival. Together, our findings reveal a crucial role for S100A4
      signaling pathways in maintaining the stemness properties and tumorigenicity of
      HN-CICs. Furthermore, our findings suggest that targeting S100A4 signaling may
      offer a new targeted strategy for HNSCC treatment by eliminating HN-CICs.

PMID- 21169410
TI  - The metastasis-associated microRNA miR-516a-3p is a novel therapeutic target for
      inhibiting peritoneal dissemination of human scirrhous gastric cancer.
AB  - Although aberrant microRNA (miRNA) is expressed in different types of human
      cancer tissues, its pathophysiologic role and the relevance of tumorigenesis and
      metastasis are still largely unknown. Here, we defined miRNAs involved in cancer
      metastasis (metastamirs) using an established mouse model for peritoneal
      dissemination of human scirrhous gastric carcinoma cells. Highly metastatic
      derivatives (44As3 cells) were derived from the parental cells originally
      isolated from patients (HSC-44PE cells). Using microarray analysis to identify
      differentially expressed miRNAs in 44As3 and HSC-44PE cells, we focused on miR
      516a-3p as a candidate antimetastatic miRNA (antimetastamir) whose functions in
      cancer had not been studied. We confirmed attenuated expression of miR-516a-3p in
      44As3 cells compared with HSC-44PE cells by Northern blot analysis and
      quantitative reverse transcriptase PCR. Stable ectopic overexpression in 44As3
      miR-516a-3p cells permitted identification of sulfatase 1 as a direct target of
      the miRNA, through use of the isobaric tagging reagent iTRAQ and the QSTAR Elite
      Hybrid LC-MS/MS system. Sulfatase 1 is known to remove 6-O-sulfates from heparan
      sulfate proteoglycans on the cell surface, causing release of membrane-bound Wnt
      ligands from cells. Consistent with this function, Western blot analyses revealed
      high levels of Wnt3a, Wnt5a, and nuclear beta-catenin accumulation in 44As3 cells
      but relatively reduced levels in 44As3-miR-516a-3p cells. Notably, orthotopic
      inoculation of nude mice with 44As3-miR-516a-3p cells yielded significantly
      longer survival periods compared with mice inoculated with control 44As3 cells.
      Through atelocollagen-mediated delivery of an miR-516a-3p expression vector into
      orthotopic 44As3 tumors, we documented its feasibility as a treatment agent. Our
      findings define the miRNA miR-516-3p as an antimetastamir with potential
      therapeutic applications in blocking metastatic dissemination of gastric cancers.

PMID- 21169411
TI  - FUS/TLS is a novel mediator of androgen-dependent cell-cycle progression and
      prostate cancer growth.
AB  - Progression of prostate cancer is highly dependent upon the androgen receptor
      pathway, such that knowledge of androgen-regulated proteins is vital to
      understand and combat this disease. Using a proteomic screen, we found the RNA
      binding protein FUS/TLS (Fused in Ewing's Sarcoma/Translocated in Liposarcoma) to
      be downregulated in response to androgen. FUS has recently been shown to be
      recruited by noncoding RNAs to the regulatory regions of target genes such as
      cyclin D1, in which it represses transcription by disrupting complex formation.
      Here we show that FUS has some characteristics of a putative tumor suppressor, as
      its overexpression promoted growth inhibition and apoptosis of prostate cancer
      cells, whereas its knockdown increased cell proliferation. This effect was
      reproducible in vivo, such that increasing FUS levels in tumor xenografts led to
      dramatic tumor regression. Furthermore, FUS promoted conditions that favored cell
      cycle arrest by reducing the levels of proliferative factors such as cyclin D1
      and Cdk6 and by increasing levels of the antiproliferative Cdk inhibitor p27.
      Immunohistochemical analysis revealed that FUS expression is inversely correlated
      with Gleason grade, demonstrating that patients with high levels of FUS survived
      longer and were less likely to have bone metastases, suggesting that loss of FUS
      expression may contribute to cancer progression. Taken together, our results
      address the question of how androgens regulate cell-cycle progression, by
      demonstrating that FUS is a key link between androgen receptor signaling and cell
      cycle progression in prostate cancer.

PMID- 21169412
TI  - Nm23-h1 indirectly promotes the survival of acute myeloid leukemia blast cells by
      binding to more mature components of the leukemic clone.
AB  - Nm23-H1 plays complex roles in the development of diverse cancers including
      breast carcinoma, high-grade lymphomas, and acute myeloid leukemia (AML). In the
      case of AML and lymphomas, serum Nm23-H1 protein is elevated with the highest
      levels correlating with poorest prognosis. A recent study identified that this
      association is most likely causal in AML and that Nm23-H1 acts as an AML cell
      survival factor. In this study, we report heterogeneity in the ability of AML
      samples to bind and respond to Nm23-H1, and we offer evidence that binding is
      essential for improved survival. Further, we show that the subset of AMLs that
      bind Nm23-H1 do not do so through the putative Nm23-H1 receptor MUC1*. Although
      rNm23-H1 promoted the survival of the most primitive blasts within responding
      AMLs, it was not these cells that actually bound the protein. Instead, rNm23-H1
      bound to more mature CD34(lo)/CD34(-) and CD11b(+) cells, revealing an indirect
      survival benefit of Nm23-H1 on primitive blasts. In support of this finding, the
      survival of purified blast cells was enhanced by medium conditioned by more
      mature cells from the clone that had been stimulated by rNm23-H1. Levels of
      interleukin 1beta (IL1beta) and IL6 in rNm23-H1 conditioned medium mirrored the
      potency of the conditioned media to promote blast cell survival. Furthermore,
      Nm23-H1 expression was significantly associated with IL1beta and IL6 expression
      in primary uncultured AML samples. These findings have implications for the role
      of Nm23-H1 in AML and its use as a prognostic marker. Additionally, they offer
      the first evidence of novel cross-talk between cell populations within the tumor
      clone.

PMID- 21169413
TI  - The molecular basis of synergism between carboplatin and ABT-737 therapy
      targeting ovarian carcinomas.
AB  - Resistance to standard chemotherapy (carboplatin + paclitaxel) is one of the
      leading causes of therapeutic failure in ovarian carcinomas. Emergence of
      chemoresistance has been shown to be mediated in part by members of the Bcl
      family of proteins including the antiapoptotic protein Bcl-x(L), whose expression
      is correlated with shorter disease-free intervals in recurrent disease. ABT-737
      is an example of one of the first small-molecule inhibitors of Bcl-2/Bcl-x(L)
      that has been shown to increase the sensitivity of ovarian cancer cells to
      carboplatin. To exploit the therapeutic potential of these two drugs and predict
      optimal doses and dose scheduling, it is essential to understand the molecular
      basis of their synergistic action. Here, we build and calibrate a mathematical
      model of ABT-737 and carboplatin action on an ovarian cancer cell line (IGROV-1).
      The model suggests that carboplatin treatment primes cells for ABT-737 therapy
      because of an increased dependence of cells with DNA damage on Bcl-x(L) for
      survival. Numerical simulations predict the existence of a threshold of Bcl-x(L)
      below which these cells are unable to recover. Furthermore, co- plus
      posttreatment of ABT-737 with carboplatin is predicted to be the best strategy to
      maximize synergism between these two drugs. A critical challenge in chemotherapy
      is to strike a balance between maximizing cell-kill while minimizing patient drug
      load. We show that the model can be used to compute minimal doses required for
      any desired fraction of cell kill. These results underscore the potential of the
      modeling work presented here as a valuable quantitative tool to aid in the
      translation of novel drugs such as ABT-737 from the experimental to clinical
      setting and highlight the need for close collaboration between modelers and
      experimental scientists.

PMID- 21169414
TI  - Activation of NF-{kappa}B by TMPRSS2/ERG Fusion Isoforms through Toll-Like
      Receptor-4.
AB  - The TMPRSS2/ERG (T/E) fusion gene is present and thought to be an oncogenic
      driver of approximately half of all prostate cancers. Fusion of the androgen
      regulated TMPRSS2 promoter to the ERG oncogene results in constitutive high level
      expression of ERG which promotes prostate cancer invasion and proliferation.
      Here, we report the characterization of multiple alternatively spliced T/E fusion
      gene isoforms which have differential effects on invasion and proliferation. We
      found that T/E fusion gene isoforms differentially increase NF-kappaB-mediated
      transcription, which may explain in part the differences in biological activities
      of the T/E fusion isoforms. This increased activity is due to phosphorylation of
      NF-kappaB p65 on Ser536. Tissue microarray immunochemistry revealed that p65
      phospho-Ser536 is present in the majority of prostate cancers where it is
      associated with ERG protein expression. The T/E fusion gene isoforms
      differentially increase expression of a number of NF-kappaB associated genes
      including PAR1, CCL2, FOS, TLR3, and TLR4 (Toll-like receptor). TLR4 activation
      is known to promote p65 Ser536 phosphorylation and knockdown of TLR4 with shRNA
      decreases Ser536 phosphorylation in T/E fusion gene expressing cells. TLR4 can be
      activated by proteins in the tumor microenvironment and lipopolysacharide from
      Gram (-) bacteria. Our findings suggest that bacterial infection of the prostate
      and/or endogenous microenvironment proteins may promote progression of high-grade
      prostatic intraepithelial neoplasia and/or prostate cancers that express the T/E
      fusion gene, where the NF-kappaB pathway might be targeted as a rational
      therapeutic approach.

PMID- 21169415
TI  - Expression of functional KISS1 and KISS1R system is altered in human pituitary
      adenomas: evidence for apoptotic action of kisspeptin-10.
AB  - CONTEXT: KISS1 was originally identified as a metastasis-suppressor gene able to
      inhibit tumor progression. KISS1 gene products, the kisspeptins, bind to a G
      protein-coupled receptor (KISS1R, formerly GPR54), which is highly expressed in
      placenta, pituitary, and pancreas, whereas KISS1 mRNA is mainly expressed in
      placenta, hypothalamus, striatum, and pituitary. OBJECTIVE AND DESIGN:
      KISS1/KISS1R pituitary expression profile, coupled to their anti-tumoral
      capacities, led us to hypothesize that this system may be involved in the biology
      of pituitary tumors. To explore this notion, expression levels of KISS1R and
      KISS1 were evaluated in normal and adenomatous pituitaries. Additionally,
      functionality of this system was assessed by treating dispersed pituitary adenoma
      cells in primary culture with kisspeptin-10 and evaluating intracellular calcium
      kinetics and apoptotic rate. RESULTS: Both KISS1 and KISS1R were expressed in
      normal pituitary, whereas this simultaneous expression was frequently lost in
      pituitary tumors, where diverse patterns of KISS1/KISS1R expression were observed
      that differed among distinct types of pituitary adenomas. Measurement of calcium
      kinetics revealed that kisspeptin-10 elicits a remarkable increase in [Ca(2+)](i)
      in individual cells from four out of the five GH-producing adenomas studied,
      whereas cells derived from non-functioning pituitary adenomas (NFPA, n=45) did
      not respond. In contrast, kisspeptin-10 treatment increased the apoptotic rate in
      cells derived from both GH-producing and NFPA. CONCLUSIONS: These results provide
      primary evidence that KISS1 and KISS1R expression can be differentially lost in
      pituitary tumor subtypes, where this system can exert functional, proapoptotic
      actions, and thereby offer novel insights to investigate the biology and
      therapeutic options to treat these tumors.

PMID- 21169416
TI  - Biochemical and genetic evidence for the presence of multiple
      phosphatidylinositol- and phosphatidylinositol 4,5-bisphosphate-specific
      phospholipases C in Tetrahymena.
AB  - Eukaryotic phosphoinositide-specific phospholipases C (PI-PLC) specifically
      hydrolyze phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)], produce the
      Ca(2+)-mobilizing agent inositol 1,4,5-trisphosphate, and regulate signaling in
      multicellular organisms. Bacterial PtdIns-specific PLCs, also present in
      trypanosomes, hydrolyze PtdIns and glycosyl-PtdIns, and they are considered
      important virulence factors. All unicellular eukaryotes studied so far contain a
      single PI-PLC-like gene. In this report, we show that ciliates are an exception,
      since we provide evidence that Tetrahymena species contain two sets of functional
      genes coding for both bacterial and eukaryotic PLCs. Biochemical characterization
      revealed two PLC activities that differ in their phosphoinositide substrate
      utilization, subcellular localization, secretion to extracellular space, and
      sensitivity to Ca(2+). One of these activities was identified as a typical
      membrane-associated PI-PLC activated by low-micromolar Ca(2+), modestly activated
      by GTPgammaS in vitro, and inhibited by the compound U73122 [1-(6-{[17beta-3
      methoxyestra-1,3,5(10)-trien-17-yl]amino}hexyl)-1H-pyrrole-2,5-dione].
      Importantly, inhibition of PI-PLC in vivo resulted in rapid upregulation of
      PtdIns(4,5)P(2) levels, suggesting its functional importance in regulating
      phosphoinositide turnover in Tetrahymena. By in silico and molecular analysis, we
      identified two PLC genes that exhibit significant similarity to bacterial but not
      trypanosomal PLC genes and three eukaryotic PI-PLC genes, one of which is a novel
      inactive PLC similar to proteins identified only in metazoa. Comparative studies
      of expression patterns and PI-PLC activities in three T. thermophila strains
      showed a correlation between expression levels and activity, suggesting that the
      three eukaryotic PI-PLC genes are functionally nonredundant. Our findings imply
      the presence of a conserved and elaborate PI-PLC-Ins(1,4,5)P(3)-Ca(2+) regulatory
      axis in ciliates.

PMID- 21169417
TI  - Differential regulation of the cellulase transcription factors XYR1, ACE2, and
      ACE1 in Trichoderma reesei strains producing high and low levels of cellulase.
AB  - Due to its capacity to produce large amounts of cellulases, Trichoderma reesei is
      increasingly being investigated for second-generation biofuel production from
      lignocellulosic biomass. The induction mechanisms of T. reesei cellulases have
      been described recently, but the regulation of the genes involved in their
      transcription has not been studied thoroughly. Here we report the regulation of
      expression of the two activator genes xyr1 and ace2, and the corepressor gene
      ace1, during the induction of cellulase biosynthesis by the inducer lactose in T.
      reesei QM 9414, a strain producing low levels of cellulase (low producer). We
      show that all three genes are induced by lactose. xyr1 was also induced by d
      galactose, but this induction was independent of d-galactose metabolism.
      Moreover, ace1 was carbon catabolite repressed, whereas full induction of xyr1
      and ace2 in fact required CRE1. Significant differences in these regulatory
      patterns were observed in the high-producer strain RUT C30 and the hyperproducer
      strain T. reesei CL847. These observations suggest that a strongly elevated basal
      transcription level of xyr1 and reduced upregulation of ace1 by lactose may have
      been important for generating the hyperproducer strain and that thus, these genes
      are major control elements of cellulase production.

PMID- 21169418
TI  - Systematic screen of Schizosaccharomyces pombe deletion collection uncovers
      parallel evolution of the phosphate signal transduction pathway in yeasts.
AB  - The phosphate signal transduction (PHO) pathway, which regulates genes in
      response to phosphate starvation, is well defined in Saccharomyces cerevisiae. We
      asked whether the PHO pathway was the same in the distantly related fission yeast
      Schizosaccharomyces pombe. We screened a deletion collection for mutants aberrant
      in phosphatase activity, which is primarily a consequence of pho1(+)
      transcription. We identified a novel zinc finger-containing protein (encoded by
      spbc27b12.11c(+)), which we have named pho7(+), that is essential for pho1(+)
      transcriptional induction during phosphate starvation. Few of the S. cerevisiae
      genes involved in the PHO pathway appear to be involved in the regulation of the
      phosphate starvation response in S. pombe. Only the most upstream genes in the
      PHO pathway in S. cerevisiae (ADO1, DDP1, and PPN1) share a similar role in both
      yeasts. Because ADO1 and DDP1 regulate ATP and IP(7) levels, we hypothesize that
      the ancestor of these yeasts must have sensed similar metabolites in response to
      phosphate starvation but have evolved distinct mechanisms in parallel to sense
      these metabolites and induce phosphate starvation genes.

PMID- 21169419
TI  - PKA and PKC are required for long-term but not short-term in vivo operant memory
      in Aplysia.
AB  - We investigated the involvement of PKA and PKC signaling in a negatively
      reinforced operant learning paradigm in Aplysia, learning that food is inedible
      (LFI). In vivo injection of PKA or PKC inhibitors blocked long-term LFI memory
      formation. Moreover, a persistent phase of PKA activity, although not PKC
      activity, was necessary for long-term memory. Surprisingly, neither PKA nor PKC
      activity was required for associative short-term LFI memory. Additionally, PKA
      and PKC were not required for the retrieval of short- or long-term memory (STM
      and LTM, respectively). These studies have identified key differences between the
      mechanisms underlying nonassociative sensitization, operant reward learning, and
      LFI memory in Aplysia.

PMID- 21169421
TI  - Direct suppression of Pth gene expression by the vitamin D prohormones
      doxercalciferol and calcidiol requires the vitamin D receptor.
AB  - Vitamin D compounds regulate PTH at the transcriptional level, presumably via
      binding to the vitamin D receptor (VDR), but the exact mechanism is presently
      unclear. We recently reported that the several vitamin D prohormones with low VDR
      affinity suppressed PTH, even when their activation was inhibited, raising the
      possibility that their actions may be VDR independent. To test this hypothesis,
      we developed a novel organ culture that allowed the assessment of activities of
      the prohormones on PTH release from wild-type and VDR-null thyroparathyroid
      explants. The cultures remained viable with respect to PTH release for at least 2
      weeks. Full suppression of PTH by the native vitamin D hormone, 1alpha,25
      dihydroxyvitamin D(3) [1alpha,25 (OH)(2)D(3)], required 2 days, consistent with a
      transcriptional mechanism, and was reversible, indicating that reduced PTH was
      not attributable to cell death. Inhibition of PTH release by 1alpha,25
      (OH)(2)D(3) and two prohormones, 25-hydroxyvitamin D(3) and 1alpha-hydroxyvitamin
      D(2), was observed in explants from wild-type mice but not in those from VDR-null
      mice. These findings 1) are the first direct demonstration of the role of the VDR
      in regulation of PTH by 1alpha,25(OH)(2)D(3), 2) confirm that the suppressive
      actions of the vitamin D prohormones are mediated by the VDR, and 3) introduce a
      novel organ culture model that allows the ex vivo study of the function of
      parathyroid glands from transgenic animals.

PMID- 21169420
TI  - MDM2 regulates estrogen receptor alpha and estrogen responsiveness in breast
      cancer cells.
AB  - Murine double minute clone 2 (MDM2) is a multifunctional protein, which modulates
      nuclear receptor-mediated transactivation. In this study, we show that MDM2
      significantly enhanced estrogen receptor alpha (ERalpha) and ERalpha/specificity
      protein-mediated transactivation in MCF-7 and ZR-75 breast cancer cells. This was
      demonstrated by both MDM2 overexpression and knockdown experiments by RNA
      interference. ERalpha interacted with wild-type MDM2 and deletion mutants of MDM2
      containing amino acids 1-342 (C-terminal deletion) and 134-490 (N-terminal
      deletion), but not 134-342. In contrast, only wild-type but not mutant MDM2
      enhanced ERalpha-mediated transactivation. Protein-protein interactions in vitro
      were 17beta-estradiol (E(2)) independent, whereas fluorescent resonance energy
      transfer experiments in living cells showed that E(2) enhanced ERalpha-MDM2
      interactions. Subsequent RNA interference and mammalian two-hybrid experiments
      suggested that MDM2 did not directly interact with endogenous coactivators such
      as the steroid receptor coactivators but played a role in enhancing ERalpha
      mediating gene expression and estrogen responsiveness through interactions with
      ERalpha.

PMID- 21169422
TI  - Ghrelin and lipid metabolism: key partners in energy balance.
AB  - Ghrelin, the endogenous ligand of the GH secretagogue receptor, has a pleiotropic
      role in the modulation of energy balance. Recent evidence has demonstrated that
      besides its orexigenic role, ghrelin regulates central and peripheral lipid
      metabolism through specific control of hypothalamic AMP-activated protein kinase
      (AMPK), a critical metabolic gauge regulating both cellular and whole-body energy
      homeostasis. In this review, we summarize the new milestones of ghrelin's actions
      on energy balance, with particular focus on its molecular interaction with
      hypothalamic AMPK and fatty acid metabolism. Understanding this new metabolic
      pathway can provide new therapeutic targets for the treatment of obesity and the
      metabolic syndrome.

PMID- 21169423
TI  - Full-text publication of abstract-presented work in physical therapy: do
      therapists publish what they preach?
AB  - BACKGROUND AND OBJECTIVE: Professional meetings, such as the American Physical
      Therapy Association's (APTA's) Combined Sections Meeting (CSM), provide forums
      for sharing information relevant to physical therapy. An indicator of whether
      therapists fully disseminate their work is the number of full-text peer-reviewed
      publications that result. The purposes of this study were: (1) to determine the
      full-text publication rate of work presented in abstract form at CSM and (2) to
      investigate factors influencing this rate. METHODS: A systematic search was
      undertaken to locate full-text publications of work presented in abstract form
      within the Orthopaedic and Sports Physical Therapy sections at CSM between 2000
      and 2004. Eligible publications were published within 5 years following abstract
      presentation. The influences of APTA section, year of abstract presentation,
      institution of origin, study design, sample size, study significance, reporting
      of a funding source, and presentation type on full-text publication rate were
      assessed. Characteristics of full-text publications were explored. RESULTS: Work
      presented in 1 out of 4 abstracts (25.4%) progressed to full-text publication.
      Odds of full-text publication increased if the abstract originated from a
      doctorate-granting or "other" institution, reported findings of an experimental
      study, reported a statistically significant finding, included a larger sample
      size, disclosed a funding source, or was presented as a platform presentation.
      More than one third (37.8%) of full-text publications were published in the
      Journal of Orthopaedic and Sports Physical Therapy or Physical Therapy, and 4 out
      of 10 full-text publications (39.2%) contained at least one major change from
      information presented in abstract form. CONCLUSIONS: The full-text publication
      rate for information presented in abstract form within the Orthopaedic and Sports
      Physical Therapy sections at CSM is low relative to comparative disciplines.
      Caution should be exercised when translating information presented at CSM into
      practice.

PMID- 21169424
TI  - The revised research agenda for physical therapy.

PMID- 21169426
TI  - Beta-1,3-glucanase from Delftia tsuruhatensis strain MV01 and its potential
      application in vinification.
AB  - During vinification microbial activities can spoil wine quality. As the wine
      related lactic acid bacterium Pediococcus parvulus is able to produce slimes
      consisting of a beta-1,3-glucan, must and wine filtration can be difficult or
      impossible. In addition, the metabolic activities of several wild-type yeasts can
      also negatively affect wine quality. Therefore, there is a need for measures to
      degrade the exopolysaccharide from Pediococcus parvulus and to inhibit the growth
      of certain yeasts. We examined an extracellular beta-1,3-glucanase from Delftia
      tsuruhatensis strain MV01 with regard to its ability to hydrolyze both polymers,
      the beta-1,3-glucan from Pediococcus and that from yeast cell walls. The 29-kDa
      glycolytic enzyme was purified to homogeneity. It exhibited an optimal activity
      at 50 degrees C and pH 4.0. The sequencing of the N terminus revealed significant
      similarities to beta-1,3-glucanases from different bacteria. In addition, the
      investigations indicated that this hydrolytic enzyme is still active under wine
      relevant parameters such as elevated ethanol, sulfite, and phenol concentrations
      as well as at low pH values. Therefore, the characterized enzyme seems to be a
      useful tool to prevent slime production and undesirable yeast growth during
      vinification.

PMID- 21169425
TI  - Transcriptional and proteomic responses of Pseudomonas aeruginosa PAO1 to
      spaceflight conditions involve Hfq regulation and reveal a role for oxygen.
AB  - Assessing bacterial behavior in microgravity is important for risk assessment and
      prevention of infectious diseases during spaceflight missions. Furthermore, this
      research field allows the unveiling of novel connections between low-fluid-shear
      regions encountered by pathogens during their natural infection process and
      bacterial virulence. This study is the first to characterize the spaceflight
      induced global transcriptional and proteomic responses of Pseudomonas aeruginosa,
      an opportunistic pathogen that is present in the space habitat. P. aeruginosa
      responded to spaceflight conditions through differential regulation of 167 genes
      and 28 proteins, with Hfq as a global transcriptional regulator. Since Hfq was
      also differentially regulated in spaceflight-grown Salmonella enterica serovar
      Typhimurium, Hfq represents the first spaceflight-induced regulator acting across
      bacterial species. The major P. aeruginosa virulence-related genes induced in
      spaceflight were the lecA and lecB lectin genes and the gene for
      rhamnosyltransferase (rhlA), which is involved in rhamnolipid production. The
      transcriptional response of spaceflight-grown P. aeruginosa was compared with our
      previous data for this organism grown in microgravity analogue conditions using
      the rotating wall vessel (RWV) bioreactor. Interesting similarities were
      observed, including, among others, similarities with regard to Hfq regulation and
      oxygen metabolism. While RWV-grown P. aeruginosa mainly induced genes involved in
      microaerophilic metabolism, P. aeruginosa cultured in spaceflight presumably
      adopted an anaerobic mode of growth, in which denitrification was most prominent.
      Whether the observed changes in pathogenesis-related gene expression in response
      to spaceflight culture could lead to an alteration of virulence in P. aeruginosa
      remains to be determined and will be important for infectious disease risk
      assessment and prevention, both during spaceflight missions and for the general
      public.

PMID- 21169427
TI  - Detection and characterization of a Cryptosporidium isolate from a southern
      elephant seal (Mirounga leonina) from the Antarctic peninsula.
AB  - The presence of Cryptosporidium and Giardia in 221 fecal samples from different
      species of Antarctic pinnipeds was investigated by immunofluorescence microscopy
      and PCR. Cryptosporidium, a skunk-like genotype, was detected only in a southern
      elephant seal. Giardia was not detected. This is the first report of a
      Cryptosporidium sp. in Antarctic marine mammals.

PMID- 21169428
TI  - Metagenomic analyses: past and future trends.
AB  - Metagenomics has revolutionized microbiology by paving the way for a cultivation
      independent assessment and exploitation of microbial communities present in
      complex ecosystems. Metagenomics comprising construction and screening of
      metagenomic DNA libraries has proven to be a powerful tool to isolate new enzymes
      and drugs of industrial importance. So far, the majority of the metagenomically
      exploited habitats comprised temperate environments, such as soil and marine
      environments. Recently, metagenomes of extreme environments have also been used
      as sources of novel biocatalysts. The employment of next-generation sequencing
      techniques for metagenomics resulted in the generation of large sequence data
      sets derived from various environments, such as soil, the human body, and ocean
      water. Analyses of these data sets opened a window into the enormous taxonomic
      and functional diversity of environmental microbial communities. To assess the
      functional dynamics of microbial communities, metatranscriptomics and
      metaproteomics have been developed. The combination of DNA-based, mRNA-based, and
      protein-based analyses of microbial communities present in different environments
      is a way to elucidate the compositions, functions, and interactions of microbial
      communities and to link these to environmental processes.

PMID- 21169429
TI  - Autophagy deficiency promotes beta-lactam production in Penicillium chrysogenum.
AB  - We have investigated the significance of autophagy in the production of the beta
      lactam antibiotic penicillin (PEN) by the filamentous fungus Penicillium
      chrysogenum. In this fungus PEN production is compartmentalized in the cytosol
      and in peroxisomes. We demonstrate that under PEN-producing conditions
      significant amounts of cytosolic and peroxisomal proteins are degraded via
      autophagy. Morphological analysis, based on electron and fluorescence microscopy,
      revealed that this phenomenon might contribute to progressive deterioration of
      late subapical cells. We show that deletion of the P. chrysogenum ortholog of
      Saccharomyces cerevisiae serine-threonine kinase atg1 results in impairment of
      autophagy. In P. chrysogenum atg1 cells, a distinct delay in cell degeneration is
      observed relative to wild-type cells. This phenomenon is associated with an
      increase in the enzyme levels of the PEN biosynthetic pathway and enhanced
      production levels of this antibacterial compound.

PMID- 21169431
TI  - Rapid, semiautomated quantification of bacterial cells in freshwater by using a
      microfluidic device for on-chip staining and counting.
AB  - A microfluidic device-based system for the rapid and semiautomated counting of
      bacteria in freshwater was fabricated and examined. Bacteria in groundwater and
      in potable water, as well as starved Escherichia coli O157:H7 spiked in pond
      water, were able to be on-chip stained and enumerated within 1 h using this
      system.

PMID- 21169430
TI  - Novel probiotic Bifidobacterium bifidum CECT 7366 strain active against the
      pathogenic bacterium Helicobacter pylori.
AB  - Helicobacter pylori is considered one of the major risk factors underlying the
      development of gastritis and gastric and duodenal ulcers. Moreover, 50% of the
      population carries this bacterium, and consequently, when it is detected,
      eradication of H. pylori is strongly recommended. Regarding the use of probiotics
      as functional agents, several studies have shown that there is a direct
      relationship between the addition of certain probiotic bacteria and in vitro
      inhibition of H. pylori; however, in vivo studies showing bifidobacterial
      activity against H. pylori remain scarce. In this study, a Bifidobacterium
      bifidum strain which proved active in vitro against H. pylori has been isolated,
      with inhibition levels reaching 81.94% in the case of the supernatant and even
      94.77% inhibition for supernatant purified by cationic exchange followed by an
      inverse phase. In vivo studies using a BALB/c mouse model have proved that this
      strain partially relieves damage to gastric tissues caused by the pathogen and
      also decreases the H. pylori pathogenicity ratio. This novel strain fulfills the
      main properties required of a probiotic (resistance to gastrointestinal juices,
      biliary salts, NaCl, and low pH; adhesion to intestinal mucus; and sensitivity to
      antibiotics). Furthermore, the absence of undesirable metabolites has been
      demonstrated, and its food safety status has been confirmed by acute ingestion
      studies in mice. In summary, the results presented here demonstrate that
      Bifidobacterium bifidum CECT 7366 can be considered a probiotic able to inhibit
      H. pylori both in vitro and in vivo.

PMID- 21169432
TI  - Natural and engineered hydroxyectoine production based on the Pseudomonas
      stutzeri ectABCD-ask gene cluster.
AB  - We report on the presence of a functional hydroxyectoine biosynthesis gene
      cluster, ectABCD-ask, in Pseudomonas stutzeri DSM5190(T) and evaluate the
      suitability of P. stutzeri DSM5190(T) for hydroxyectoine production. Furthermore,
      we present information on heterologous de novo production of the compatible
      solute hydroxyectoine in Escherichia coli. In this host, the P. stutzeri gene
      cluster remained under the control of its salt-induced native promoters. We also
      noted the absence of trehalose when hydroxyectoine genes were expressed, as well
      as a remarkable inhibitory effect of externally applied betaine on hydroxyectoine
      synthesis. The specific heterologous production rate in E. coli under the
      conditions employed exceeded that of the natural producer Pseudomonas stutzeri
      and, for the first time, enabled effective hydroxyectoine production at low
      salinity (2%), with the added advantage of simple product processing due to the
      absence of other cosolutes.

PMID- 21169434
TI  - Possible implications of chytrid parasitism for population subdivision in
      freshwater cyanobacteria of the genus Planktothrix.
AB  - Populations of the cyanobacterium Planktothrix comprise multiple coexisting
      oligopeptide chemotypes that can behave differently in nature. We tested whether
      this population subdivision can, in principle, be driven by parasitic chytrid
      fungi, which are almost neglected agents of Planktothrix mortality. Two chytrid
      strains, Chy-Lys2009 and Chy-Kol2008, were isolated from Planktothrix-dominated
      lakes in Norway. The two strains shared 98.2% and 86.2% of their 28S and internal
      transcribe spacer rRNA gene sequences, respectively. A phylogenetic analysis
      placed them in the order Rhizophydiales family Angulomycetaceae. Chy-Lys2009 and
      Chy-Kol2008 could completely lyse Planktothrix cultures within days, while they
      failed to infect other filamentous cyanobacteria. The effect on Planktothrix was
      chemotype dependent, and both chytrid strains showed distinct chemotype
      preferences. These findings identify chytrid fungi infecting Planktothrix as
      highly potent and specialized parasites which may exert strong selective pressure
      on their hosts. According to established hypotheses on host-parasite coevolution,
      parasitism with the above properties may result in subdivision of Planktothrix
      populations into coexisting chemotypes and periodic shifts in the relative
      Planktothrix chemotype composition. These predictions are in agreement with field
      observations. Moreover, a genetic analysis verified the co-occurrence of Chy
      Lys2009 and Chy-Kol2008 or related chytrid strains along with distinct
      Planktothrix chemotypes in at least one water body. Our findings are consistent
      with a scenario where chytrid parasitism is one driving force of Planktothrix
      population subdivision, which in turn leads to polymorphism in parasitic chytrid
      fungi. Future studies should test the validity of this scenario under field
      conditions.

PMID- 21169433
TI  - Influence of molecular resolution on sequence-based discovery of ecological
      diversity among Synechococcus populations in an alkaline siliceous hot spring
      microbial mat.
AB  - Previous research has shown that sequences of 16S rRNA genes and 16S-23S rRNA
      internal transcribed spacer regions may not have enough genetic resolution to
      define all ecologically distinct Synechococcus populations (ecotypes) inhabiting
      alkaline, siliceous hot spring microbial mats. To achieve higher molecular
      resolution, we studied sequence variation in three protein-encoding loci sampled
      by PCR from 60 degrees C and 65 degrees C sites in the Mushroom Spring mat
      (Yellowstone National Park, WY). Sequences were analyzed using the ecotype
      simulation (ES) and AdaptML algorithms to identify putative ecotypes. Between 4
      and 14 times more putative ecotypes were predicted from variation in protein
      encoding locus sequences than from variation in 16S rRNA and 16S-23S rRNA
      internal transcribed spacer sequences. The number of putative ecotypes predicted
      depended on the number of sequences sampled and the molecular resolution of the
      locus. Chao estimates of diversity indicated that few rare ecotypes were missed.
      Many ecotypes hypothesized by sequence analyses were different in their habitat
      specificities, suggesting different adaptations to temperature or other
      parameters that vary along the flow channel.

PMID- 21169435
TI  - The mode of cell wall growth in selected archaea is similar to the general mode
      of cell wall growth in bacteria as revealed by fluorescent dye analysis.
AB  - The surfaces of 8 bacterial and 23 archaeal species, including many
      hyperthermophilic Archaea, could be stained using succinimidyl esters of
      fluorescent dyes. This allowed us for the first time to analyze the mode of cell
      wall growth in Archaea by subculturing stained cells. The data obtained show that
      incorporation of new cell wall material in Archaea follows the pattern observed
      for Bacteria: in the coccoid species Pyrococcus furiosus incorporation was in the
      region of septum formation while for the rod-shaped species Methanopyrus kandleri
      and Methanothermus sociabilis, a diffuse incorporation of cell wall material over
      the cell length was observed. Cell surface appendages like fimbriae/pili, fibers,
      or flagella were detectable by fluorescence staining only in a very few cases
      although their presence was proven by electron microscopy. Our data in addition
      prove that Alexa Fluor dyes can be used for in situ analyses at temperatures up
      to 100 degrees C.

PMID- 21169436
TI  - Mechanism of binding of prothioconazole to Mycosphaerella graminicola CYP51
      differs from that of other azole antifungals.
AB  - Prothioconazole is one of the most important commercially available demethylase
      inhibitors (DMIs) used to treat Mycosphaerella graminicola infection of wheat,
      but specific information regarding its mode of action is not available in the
      scientific literature. Treatment of wild-type M. graminicola (strain IPO323) with
      5 MUg of epoxiconazole, tebuconazole, triadimenol, or prothioconazole ml(-1)
      resulted in inhibition of M. graminicola CYP51 (MgCYP51), as evidenced by the
      accumulation of 14alpha-methylated sterol substrates (lanosterol and eburicol)
      and the depletion of ergosterol in azole-treated cells. Successful expression of
      MgCYP51 in Escherichia coli enabled us to conduct spectrophotometric assays using
      purified 62-kDa MgCYP51 protein. Antifungal-binding studies revealed that
      epoxiconazole, tebuconazole, and triadimenol all bound tightly to MgCYP51,
      producing strong type II difference spectra (peak at 423 to 429 nm and trough at
      406 to 409 nm) indicative of the formation of classical low-spin sixth-ligand
      complexes. Interaction of prothioconazole with MgCYP51 exhibited a novel spectrum
      with a peak and trough observed at 410 nm and 428 nm, respectively, indicating a
      different mechanism of inhibition. Prothioconazole bound to MgCYP51 with 840-fold
      less affinity than epoxiconazole and, unlike epoxiconazole, tebuconazole, and
      triadimenol, which are noncompetitive inhibitors, prothioconazole was found to be
      a competitive inhibitor of substrate binding. This represents the first study to
      validate the effect of prothioconazole on the sterol composition of M.
      graminicola and the first on the successful heterologous expression of active
      MgCYP51 protein. The binding affinity studies documented here provide novel
      insights into the interaction of MgCYP51 with DMIs, especially for the new
      triazolinethione derivative prothioconazole.

PMID- 21169437
TI  - Heterogeneity of Aspergillus niger microcolonies in liquid shaken cultures.
AB  - The fungus Aspergillus niger forms (sub)millimeter microcolonies within a liquid
      shaken culture. Here, we show that such microcolonies are heterogeneous with
      respect to size and gene expression. Microcolonies of strains expressing green
      fluorescent protein (GFP) from the promoter of the glucoamlyase gene glaA or the
      ferulic acid esterase gene faeA were sorted on the basis of diameter and
      fluorescence using the Complex Object Parametric Analyzer and Sorter (COPAS)
      technology. Statistical analysis revealed that the liquid shaken culture
      consisted of two populations of microcolonies that differ by 90 MUm in diameter.
      The population of small microcolonies of strains expressing GFP from the glaA or
      faeA promoter comprised 39% and 25% of the culture, respectively. Two populations
      of microcolonies could also be distinguished when the expression of GFP in these
      strains was analyzed. The population expressing a low level of GFP consisted of
      68% and 44% of the culture, respectively. We also show that mRNA accumulation is
      heterogeneous within microcolonies of A. niger. Central and peripheral parts of
      the mycelium were isolated with laser microdissection and pressure catapulting
      (LMPC), and RNA from these samples was used for quantitative PCR analysis. This
      analysis showed that the RNA content per hypha was about 45 times higher at the
      periphery than in the center of the microcolony. Our data imply that the protein
      production of A. niger can be improved in industrial fermentations by reducing
      the heterogeneity within the culture.

PMID- 21169438
TI  - Spatial distribution of bacterial colonies in a model cheese.
AB  - In most ripened cheeses, bacteria are responsible for the ripening process.
      Immobilized in the cheese matrix, they grow as colonies. Therefore, their
      distribution as well as the distance between them are of major importance for
      ripening steps since metabolites diffuse within the cheese matrix. No data are
      available to date about the spatial distribution of bacterial colonies in cheese.
      This is the first study to model the distribution of bacterial colonies in a food
      type matrix using nondestructive techniques. We compared (i) the mean theoretical
      three-dimensional (3D) distances between colonies calculated on the basis of
      inoculation levels and considering colony distribution to be random and (ii)
      experimental measurements using confocal microscopy photographs of fluorescent
      colonies of a Lactococcus lactis strain producing green fluorescent protein (GFP)
      inoculated, at different levels, into a model cheese made by ultrafiltration
      (UF). Enumerations showed that the final numbers of cells were identical whatever
      the inoculation level (10(4) to 10(7) CFU/g). Bacterial colonies were shown to be
      randomly distributed, fitting Poisson's model. The initial inoculation level
      strongly influenced the mean distances between colonies (from 25 MUm to 250 MUm)
      and also their mean diameters. The lower the inoculation level, the larger the
      colonies were and the further away from each other. Multiplying the inoculation
      level by 50 multiplied the interfacial area of exchange with the cheese matrix by
      7 for the same cell biomass. We finally suggested that final cell numbers should
      be discussed together with inoculation levels to take into account the
      distribution and, consequently, the interfacial area of colonies, which can have
      a significant influence on the cheese-ripening process on a microscopic scale.

PMID- 21169439
TI  - High-throughput plasmid content analysis of Borrelia burgdorferi B31 by using
      Luminex multiplex technology.
AB  - Borrelia burgdorferi, the causative agent of Lyme disease in North America, is an
      invasive pathogen that causes persistent multiorgan manifestations in humans and
      other mammals. Genetic studies of this bacterium are complicated by the presence
      of multiple plasmid replicons, many of which are readily lost during in vitro
      culture. The analysis of B. burgdorferi plasmid content by plasmid-specific PCR
      and agarose gel electrophoresis or other existing techniques is informative, but
      these techniques are cumbersome and challenging to perform in a high-throughput
      manner. In this study, a PCR-based Luminex assay was developed for determination
      of the plasmid content of the strain B. burgdorferi B31. This multiplex, high
      throughput method allows simultaneous detection of the plasmid contents of many
      B. burgdorferi strains in a 96-well format. The procedure was used to evaluate
      the occurrence of plasmid loss in 44 low-passage B. burgdorferi B31 clones and in
      a library of over 4,000 signature-tagged mutagenesis (STM) transposon mutant
      clones. This analysis indicated that only 40% of the clones contained all
      plasmids, with (in order of decreasing frequency) lp5, lp56, lp28-1, lp25, cp9,
      lp28-4, lp28-2, and lp21 being the most commonly missing plasmids. These results
      further emphasize the need for careful plasmid analysis in Lyme disease Borrelia
      studies. Adaptations of this approach may also be useful in the evaluation of
      plasmid content and chromosomal gene variations in additional Lyme disease
      Borrelia strains and other organisms with variable genomes and in the correlation
      of these genetic differences with pathogenesis and other biological properties.

PMID- 21169440
TI  - Inhibition of cereulide toxin synthesis by emetic Bacillus cereus via long-chain
      polyphosphates.
AB  - Severe intoxications caused by the Bacillus cereus emetic toxin cereulide can
      hardly be prevented due to the ubiquitous distribution and heat resistance of
      spores and the extreme thermal and chemical stability of cereulide. It would
      therefore be desirable to inhibit cereulide synthesis during food manufacturing
      processes or in prepared foods, which are stored under time-temperature abuse
      conditions. Toward this end, the impacts of three long-chain polyphosphate
      (polyP) formulations on growth and cereulide production were examined. The
      inhibition was dependent on the concentration and the type of the polyP blend,
      indicating that polyPs and not the orthophosphates were effective. Quantitative
      PCR (qPCR) monitoring at sublethal concentrations revealed that polyPs reduced
      the transcription of ces nonribosomal peptide synthetase (NRPS) genes by 3- to 4
      fold along with a significantly reduced toxin production level. At lower
      concentrations, toxin synthesis was decreased, although the growth rate was not
      affected. These data indicate a differential effect on toxin synthesis
      independent of growth inhibition. The inhibition of toxin synthesis in food was
      also observed. Despite the growth of B. cereus, toxin synthesis was reduced by 70
      to 100% in two model food systems (reconstituted infant food and oat milk), which
      were analyzed with HEp-2 cell culture assays and high-performance liquid
      chromatography (HPLC)/electrospray ionization-time of flight mass spectrometry
      (ESI-TOF-MS). Accordingly, ces promoter activity was strongly downregulated, as
      visualized by using a lux-based reporter strain. These data illustrate the
      potential of polyphosphate formulations to reduce the risk of cereulide synthesis
      in food and may contribute to targeted hurdle concepts.

PMID- 21169441
TI  - Induction of a state of iron limitation in uropathogenic Escherichia coli CFT073
      by cranberry-derived proanthocyanidins as revealed by microarray analysis.
AB  - Transcriptional profiles of uropathogenic Escherichia coli CFT073 exposed to
      cranberry-derived proanthocyanidins (PACs) were determined. Our results indicate
      that bacteria grown on media supplemented with PACs were iron deprived. To our
      knowledge, this is the first time that PACs have been shown to induce a state of
      iron limitation in this bacterium.

PMID- 21169443
TI  - Lateral transfer of the denitrification pathway genes among Thermus thermophilus
      strains.
AB  - Nitrate respiration is a common and strain-specific property in Thermus
      thermophilus encoded by the nitrate respiration conjugative element (NCE) that
      can be laterally transferred by conjugation. In contrast, nitrite respiration and
      further denitrification steps are restricted to a few isolates of this species.
      These later steps of the denitrification pathway are under the regulatory control
      of an NCE-encoded transcription factor, but nothing is known about their coding
      sequences or its putative genetic linkage to the NCE. In this study we examine
      the genetic linkage between nitrate and nitrite respiration through lateral gene
      transfer (LGT) assays and describe a cluster of genes encoding the nitrite-nitric
      oxide respiration in T. thermophilus PRQ25. We show that the whole
      denitrification pathway can be transferred from the denitrificant strain PRQ25 to
      an aerobic strain, HB27, and that the genes coding for nitrite and nitric oxide
      respiration are encoded near the NCE. Sequence data from the draft genome of
      PRQ25 confirmed these results and allowed us to describe the most compact nor-nir
      cluster known thus far and to demonstrate the expression and activities of the
      encoded enzymes in the HB27 denitrificant derivatives obtained by LGT. We
      conclude that this NCE nor-nir supercluster constitutes a whole denitrification
      island that can be spread by lateral transfer among Thermus thermophilus strains.

PMID- 21169442
TI  - Variation in Listeria monocytogenes dose responses in relation to subtypes
      encoding a full-length or truncated internalin A.
AB  - Internalin A (InlA; encoded by inlA) facilitates the crossing of the intestinal
      barrier by Listeria monocytogenes. Mutations leading to a premature stop codon
      (PMSC) in inlA and thus attenuated mammalian virulence have been reported. We
      recently characterized 502 L. monocytogenes food isolates from a retail survey
      and 507 human clinical isolates from multiple U.S. states with respect to the
      presence/absence of inlA mutations. The objective of this study was to
      investigate the hypothesis that dose responses for human listeriosis vary between
      L. monocytogenes strains with and those without a PMSC in inlA. Subtype-specific
      prevalence and concentration distributions in food, along with epidemiologic and
      consumption data, were input into established dose-response models to generate an
      r value (probability of a cell causing illness). Under the conservative
      assumption that L. monocytogenes levels at retail represent levels consumed, mean
      log(10) r values were -8.1 and -10.7 for L. monocytogenes subtypes with genes
      encoding a full-length and a truncated InlA, respectively. L. monocytogenes
      carrying a 5' frameshift mutation in a homopolymeric tract showed a mean log(10)
      r value of -12.1. Confidence intervals for the r values and their differences
      varied depending on subtypes. When the increase in concentration of L.
      monocytogenes subtypes between retail and consumption was considered, mean
      log(10) r values were reduced to -10.4, -13.8, and -12.8 for the subtypes with
      genes encoding a full-length InlA, for the subtypes carrying a PMSC in inlA, and
      for all L. monocytogenes isolates regardless of subtype, respectively. Our study
      provides further quantitative evidence that L. monocytogenes subtypes vary in
      abilities and relative likelihoods of causing human disease, which were
      mechanistically related to defined genetic markers.

PMID- 21169444
TI  - Bacterial communities associated with the lichen symbiosis.
AB  - Lichens are commonly described as a mutualistic symbiosis between fungi and
      "algae" (Chlorophyta or Cyanobacteria); however, they also have internal
      bacterial communities. Recent research suggests that lichen-associated microbes
      are an integral component of lichen thalli and that the classical view of this
      symbiotic relationship should be expanded to include bacteria. However, we still
      have a limited understanding of the phylogenetic structure of these communities
      and their variability across lichen species. To address these knowledge gaps, we
      used bar-coded pyrosequencing to survey the bacterial communities associated with
      lichens. Bacterial sequences obtained from four lichen species at multiple
      locations on rock outcrops suggested that each lichen species harbored a distinct
      community and that all communities were dominated by Alphaproteobacteria. Across
      all samples, we recovered numerous bacterial phylotypes that were closely related
      to sequences isolated from lichens in prior investigations, including those from
      a lichen-associated Rhizobiales lineage (LAR1; putative N(2) fixers). LAR1
      related phylotypes were relatively abundant and were found in all four lichen
      species, and many sequences closely related to other known N(2) fixers (e.g.,
      Azospirillum, Bradyrhizobium, and Frankia) were recovered. Our findings confirm
      the presence of highly structured bacterial communities within lichens and
      provide additional evidence that these bacteria may serve distinct functional
      roles within lichen symbioses.

PMID- 21169445
TI  - Heterologously expressed family 51 alpha-L-arabinofuranosidases from Oenococcus
      oeni and Lactobacillus brevis.
AB  - Putative alpha-L-arabinofuranosidases of Oenococcus oeni and Lactobacillus brevis
      were heterologously expressed and characterized. We report the basic functional
      properties of the recombinant enzymes in comparison to those of a commercial
      family 51 arabinosidase of Aspergillus niger.

PMID- 21169446
TI  - Different substrate recognition requirements for cleavage of synaptobrevin-2 by
      Clostridium baratii and Clostridium botulinum type F neurotoxins.
AB  - Botulinum neurotoxins (BoNTs) cause botulism, which can be fatal if it is
      untreated. BoNTs cleave proteins necessary for nerve transmission, resulting in
      paralysis. The in vivo protein target has been reported for all seven serotypes
      of BoNT, i.e., serotypes A to G. Knowledge of the cleavage sites has led to the
      development of several assays to detect BoNT based on its ability to cleave a
      peptide substrate derived from its in vivo protein target. Most serotypes of BoNT
      can be subdivided into subtypes, and previously, we demonstrated that three of
      the currently known subtypes of BoNT/F cleave a peptide substrate, a shortened
      version of synaptobrevin-2, between Q58 and K59. However, our research indicated
      that Clostridium baratii type F toxin did not cleave this peptide. In this study,
      we detail experiments demonstrating that Clostridium baratii type F toxin cleaves
      recombinant synaptobrevin-2 in the same location as that cleaved by proteolytic F
      toxin. In addition, we demonstrate that Clostridium baratii type F toxin can
      cleave a peptide substrate based on the sequence of synaptobrevin-2. This peptide
      substrate is an N-terminal extension of the original peptide substrate used for
      detection of other BoNT/F toxins and can be used to detect four of the currently
      known BoNT/F subtypes by mass spectrometry.

PMID- 21169447
TI  - Extension of the substrate utilization range of Ralstonia eutropha strain H16 by
      metabolic engineering to include mannose and glucose.
AB  - The gram-negative facultative chemolithoautotrophic bacterium Ralstonia eutropha
      strain H16 is known for its narrow carbohydrate utilization range, which limits
      its use for biotechnological production of polyhydroxyalkanoates and possibly
      other products from renewable resources. To broaden its substrate utilization
      range, which is for carbohydrates and related compounds limited to fructose, N
      acetylglucosamine, and gluconate, strain H16 was engineered to use mannose and
      glucose as sole carbon sources for growth. The genes for a facilitated diffusion
      protein (glf) from Zymomonas mobilis and for a glucokinase (glk),
      mannofructokinase (mak), and phosphomannose isomerase (pmi) from Escherichia coli
      were alone or in combination constitutively expressed in R. eutropha strain H16
      under the control of the neokanamycin or lac promoter, respectively, using an
      episomal broad-host-range vector. Recombinant strains harboring pBBR1MCS
      3::glf::mak::pmi or pBBR1MCS-3::glf::pmi grew on mannose, whereas pBBR1MCS
      3::glf::mak and pBBR1MCS-3::glf did not confer the ability to utilize mannose as
      a carbon source to R. eutropha. The recombinant strain harboring pBBR1MCS
      3::glf::pmi exhibited slower growth on mannose than the recombinant strain
      harboring pBBR1MCS-3::glf::mak::pmi. These data indicated that phosphomannose
      isomerase is required to convert mannose-6-phosphate into fructose-6-phosphate
      for subsequent catabolism via the Entner-Doudoroff pathway. In addition, all
      plasmids also conferred to R. eutropha the ability to grow in the presence of
      glucose. The best growth was observed with a recombinant R. eutropha strain
      harboring plasmid pBBR1MCS-2::P(nk)::glk::glf. In addition, expression of the
      respective enzymes was demonstrated at the transcriptional and protein levels and
      by measuring the activities of mannofructokinase (0.622 +/- 0.063 U mg(-1)),
      phosphomannose isomerase (0.251 +/- 0.017 U mg(-1)), and glucokinase (0.518 +/-
      0.040 U mg(-1)). Cells of recombinant strains of R. eutropha synthesized poly(3
      hydroxybutyrate) to ca. 65 to 67% (wt/wt) of the cell dry mass in the presence of
      1% (wt/vol) glucose or mannose as the sole carbon sources.

PMID- 21169448
TI  - Developmental penalties associated with inducible tolerance in Helicoverpa
      armigera to insecticidal toxins from Bacillus thuringiensis.
AB  - Exposure of insect larvae to sublethal concentrations of crystal toxins from the
      soil bacterium Bacillus thuringiensis (Bt toxins) causes the induction of immune
      and metabolic responses that can be transmitted to offspring by epigenetic
      inheritance mechanisms. Given that the elevated immune status carries significant
      developmental penalties, we wanted to establish the relationships between immune
      induction, tolerance to the toxin and developmental penalties. A laboratory
      culture of Helicoverpa armigera was induced by a sublethal bacterial suspension
      containing crystal toxin Cry1Ac in one generation and maintained in the presence
      of toxin, acquiring significant levels of tolerance to the toxin within 12
      generations of continuous exposure. Comparing tolerant and susceptible insects,
      we show that the induction of larval immune response and the coincident
      alteration of development-related metabolic activities by elicitors in the larval
      gut (larval induction) differs from the elevated immune status transmitted by
      epigenetic mechanisms (embryonic induction). Because the damaging effects of
      larval induction processes are higher compared to embryonic induction, it is
      likely that overall developmental penalties depend on the relative contribution
      of the two induction processes. When insects are kept with the same amount of
      toxin in the diet for subsequent generations, the embryonic induction process
      increases its contribution compared to the larval induction, resulting in reduced
      overall developmental penalty, while tolerance to the toxin is maintained.

PMID- 21169449
TI  - Involvement of the Shewanella oneidensis decaheme cytochrome MtrA in the
      periplasmic stability of the beta-barrel protein MtrB.
AB  - The Shewanella oneidensis outer membrane beta-barrel protein MtrB is part of a
      membrane-spanning protein complex (MtrABC) which is necessary for dissimilatory
      iron reduction. Quantitative PCR, heterologous gene expression, and mutant
      studies indicated that MtrA is required for periplasmic stability of MtrB. DegP
      depletion compensated for this MtrA dependence.

PMID- 21169450
TI  - Global regulation of the response to sulfur availability in the cheese-related
      bacterium Brevibacterium aurantiacum.
AB  - In this study, we combined metabolic reconstruction, growth assays, and
      metabolome and transcriptome analyses to obtain a global view of the sulfur
      metabolic network and of the response to sulfur availability in Brevibacterium
      aurantiacum. In agreement with the growth of B. aurantiacum in the presence of
      sulfate and cystine, the metabolic reconstruction showed the presence of a
      sulfate assimilation pathway, thiolation pathways that produce cysteine (cysE and
      cysK) or homocysteine (metX and metY) from sulfide, at least one gene of the
      transsulfuration pathway (aecD), and genes encoding three MetE-type methionine
      synthases. We also compared the expression profiles of B. aurantiacum ATCC 9175
      during sulfur starvation or in the presence of sulfate. Under sulfur starvation,
      690 genes, including 21 genes involved in sulfur metabolism and 29 genes encoding
      amino acids and peptide transporters, were differentially expressed. We also
      investigated changes in pools of sulfur-containing metabolites and in expression
      profiles after growth in the presence of sulfate, cystine, or methionine plus
      cystine. The expression of genes involved in sulfate assimilation and cysteine
      synthesis was repressed in the presence of cystine, whereas the expression of
      metX, metY, metE1, metE2, and BL613, encoding a probable cystathionine-gamma
      synthase, decreased in the presence of methionine. We identified three ABC
      transporters: two operons encoding transporters were transcribed more strongly
      during cysteine limitation, and one was transcribed more strongly during
      methionine depletion. Finally, the expression of genes encoding a methionine
      gamma-lyase (BL929) and a methionine transporter (metPS) was induced in the
      presence of methionine in conjunction with a significant increase in volatile
      sulfur compound production.

PMID- 21169451
TI  - Imaging hydrated microbial extracellular polymers: comparative analysis by
      electron microscopy.
AB  - Microbe-mineral and -metal interactions represent a major intersection between
      the biosphere and geosphere but require high-resolution imaging and analytical
      tools for investigation of microscale associations. Electron microscopy has been
      used extensively for geomicrobial investigations, and although used bona fide,
      the traditional methods of sample preparation do not preserve the native
      morphology of microbiological components, especially extracellular polymers.
      Herein, we present a direct comparative analysis of microbial interactions by
      conventional electron microscopy approaches with imaging at room temperature and
      a suite of cryogenic electron microscopy methods providing imaging in the close
      to-natural hydrated state. In situ, we observed an irreversible transformation of
      the hydrated bacterial extracellular polymers during the traditional dehydration
      based sample preparation that resulted in their collapse into filamentous
      structures. Dehydration-induced polymer collapse can lead to inaccurate spatial
      relationships and hence could subsequently affect conclusions regarding the
      nature of interactions between microbial extracellular polymers and their
      environment.

PMID- 21169452
TI  - Microorganisms with novel dissimilatory (bi)sulfite reductase genes are
      widespread and part of the core microbiota in low-sulfate peatlands.
AB  - Peatlands of the Lehstenbach catchment (Germany) house as-yet-unidentified
      microorganisms with phylogenetically novel variants of the dissimilatory
      (bi)sulfite reductase genes dsrAB. These genes are characteristic of
      microorganisms that reduce sulfate, sulfite, or some organosulfonates for energy
      conservation but can also be present in anaerobic syntrophs. However, nothing is
      currently known regarding the abundance, community dynamics, and biogeography of
      these dsrAB-carrying microorganisms in peatlands. To tackle these issues, soils
      from a Lehstenbach catchment site (Schloppnerbrunnen II fen) from different
      depths were sampled at three time points over a 6-year period to analyze the
      diversity and distribution of dsrAB-containing microorganisms by a newly
      developed functional gene microarray and quantitative PCR assays. Members of
      novel, uncultivated dsrAB lineages (approximately representing species-level
      groups) (i) dominated a temporally stable but spatially structured dsrAB
      community and (ii) represented "core" members (up to 1% to 1.7% relative
      abundance) of the autochthonous microbial community in this fen. In addition,
      denaturing gradient gel electrophoresis (DGGE)- and clone library-based
      comparisons of the dsrAB diversity in soils from a wet meadow, three bogs, and
      five fens of various geographic locations (distance of ~1 to 400 km) identified
      that one Syntrophobacter-related and nine novel dsrAB lineages are widespread in
      low-sulfate peatlands. Signatures of biogeography in dsrB-based DGGE data were
      not correlated with geographic distance but could be explained largely by soil pH
      and wetland type, implying that the distribution of dsrAB-carrying microorganisms
      in wetlands on the scale of a few hundred kilometers is not limited by dispersal
      but determined by local environmental conditions.

PMID- 21169453
TI  - Bioprospecting for trichothecene 3-O-acetyltransferases in the fungal genus
      Fusarium yields functional enzymes with different abilities to modify the
      mycotoxin deoxynivalenol.
AB  - The trichothecene mycotoxin deoxynivalenol (DON) is a common contaminant of small
      grains, such as wheat and barley, in the United States. New strategies to
      mitigate the threat of DON need to be developed and implemented. TRI101 and
      TRI201 are trichothecene 3-O-acetyltransferases that are able to modify DON and
      reduce its toxicity. Recent work has highlighted differences in the activities of
      TRI101 from two different species of Fusarium (F. graminearum and F.
      sporotrichioides), but little is known about the relative activities of
      TRI101/TRI201 enzymes produced by other species of Fusarium. We cloned TRI101 or
      TRI201 genes from seven different species of Fusarium and found genetic identity
      between sequences ranging from 66% to 98%. In vitro feeding studies using
      transformed yeast showed that all of the TRI101/TRI201 enzymes tested were able
      to acetylate DON; conversion of DON to 3-acetyl-deoxynivalenol (3ADON) ranged
      from 50.5% to 100.0%, depending on the Fusarium species from which the gene
      originated. A time course assay showed that the rate of acetylation varied from
      species to species, with the gene from F. sporotrichioides having the lowest
      rate. Steady-state kinetic assays using seven purified enzymes produced catalytic
      efficiencies for DON acetylation ranging from 6.8 * 10(4) M(-1).s(-1) to 4.7 *
      10(6) M(-1).s(-1). Thermostability measurements for the seven orthologs ranged
      from 37.1 degrees C to 43.2 degrees C. Extended sequence analysis of portions of
      TRI101/TRI201 from 31 species of Fusarium (including known trichothecene
      producers and nonproducers) suggested that other members of the genus may contain
      functional TRI101/TRI201 genes, some with the potential to outperform those
      evaluated in the present study.

PMID- 21169454
TI  - Comparison of family 9 cellulases from mesophilic and thermophilic bacteria.
AB  - Cellulases containing a family 9 catalytic domain and a family 3c cellulose
      binding module (CBM3c) are important components of bacterial cellulolytic
      systems. We measured the temperature dependence of the activities of three
      homologs: Clostridium cellulolyticum Cel9G, Thermobifida fusca Cel9A, and C.
      thermocellum Cel9I. To directly compare their catalytic activities, we
      constructed six new versions of the enzymes in which the three GH9-CBM3c domains
      were fused to a dockerin both with and without a T. fusca fibronectin type 3
      homology module (Fn3). We studied the activities of these enzymes on crystalline
      cellulose alone and in complex with a miniscaffoldin containing a cohesin and a
      CBM3a. The presence of Fn3 had no measurable effect on thermostability or
      cellulase activity. The GH9-CBM3c domains of Cel9A and Cel9I, however, were more
      active than the wild type when fused to a dockerin complexed to scaffoldin. The
      three cellulases in complex have similar activities on crystalline cellulose up
      to 60 degrees C, but C. thermocellum Cel9I, the most thermostable of the three,
      remains highly active up to 80 degrees C, where its activity is 1.9 times higher
      than at 60 degrees C. We also compared the temperature-dependent activities of
      different versions of Cel9I (wild type or in complex with a miniscaffoldin) and
      found that the thermostable CBM is necessary for activity on crystalline
      cellulose at high temperatures. These results illustrate the significant benefits
      of working with thermostable enzymes at high temperatures, as well as the
      importance of retaining the stability of all modules involved in cellulose
      degradation.

PMID- 21169455
TI  - Global gene expression patterns in Clostridium thermocellum as determined by
      microarray analysis of chemostat cultures on cellulose or cellobiose.
AB  - A microarray study of chemostat growth on insoluble cellulose or soluble
      cellobiose has provided substantial new information on Clostridium thermocellum
      gene expression. This is the first comprehensive examination of gene expression
      in C. thermocellum under defined growth conditions. Expression was detected from
      2,846 of 3,189 genes, and regression analysis revealed 348 genes whose changes in
      expression patterns were growth rate and/or substrate dependent. Successfully
      modeled genes included those for scaffoldin and cellulosomal enzymes,
      intracellular metabolic enzymes, transcriptional regulators, sigma factors,
      signal transducers, transporters, and hypothetical proteins. Unique genes
      encoding glycolytic pathway and ethanol fermentation enzymes expressed at high
      levels simultaneously with previously established maximal ethanol production were
      also identified. Ranking of normalized expression intensities revealed
      significant changes in transcriptional levels of these genes. The pattern of
      expression of transcriptional regulators, sigma factors, and signal transducers
      indicates that response to growth rate is the dominant global mechanism used for
      control of gene expression in C. thermocellum.

PMID- 21169456
TI  - Ochrobactrum daejeonense sp. nov., a nitrate-reducing bacterium isolated from
      sludge of a leachate treatment plant.
AB  - A Gram-reaction-negative, non-spore-forming, rod-shaped, aerobic bacterial
      strain, designated MJ11(T), was isolated from sludge of a leachate treatment
      plant in Daejeon, South Korea, and was characterized taxonomically by using a
      polyphasic approach. Comparative 16S rRNA gene sequence analysis showed that
      strain MJ11(T) belonged to the family Brucellaceae, class Alphaproteobacteria,
      and was most closely related to Ochrobactrum ciceri Ca-34(T) (97.9 % sequence
      similarity) and Ochrobactrum pituitosum CCUG 50899(T) (96.4 %). Comparative
      sequence analyses of the additional phylogenetic marker genes dnaK, groEL and
      gyrB confirmed the affiliation of strain MJ11(T) to the genus Ochrobactrum. The
      G+C content of the genomic DNA of strain MJ11(T) was 59.3 mol%. The detection of
      a quinone system with ubiquinone Q-10 as the predominant respiratory lipoquinone,
      a fatty acid profile with C(18 : 1)omega7c (62.6 %) and C(19 : 0) cyclo omega8c
      (14.2 %) as the major components, a polar lipid profile with
      phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine,
      phosphatidylmonomethylethanolamine, diphosphatidylglycerol and unknown
      aminolipids AL1 and AL2 as major polar lipids and spermidine and putrescine as
      the predominant polyamines also supported the affiliation of strain MJ11(T) to
      the genus Ochrobactrum. The DNA-DNA relatedness between strain MJ11(T) and
      Ochrobactrum ciceri DSM 22292(T) was 29 +/- 7 %, clearly showing that the isolate
      constitutes a new genospecies. Strain MJ11(T) could be clearly differentiated
      from its closest neighbours on the basis of its phenotypic, genotypic and
      chemotaxonomic features. Therefore, strain MJ11(T) represents a novel species of
      the genus Ochrobactrum, for which the name Ochrobactrum daejeonense sp. nov. is
      proposed. The type strain is MJ11(T) ( = KCTC 22458(T) = JCM 16234(T)).

PMID- 21169457
TI  - Fervidobacterium riparium sp. nov., a thermophilic anaerobic cellulolytic
      bacterium isolated from a hot spring.
AB  - A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium,
      strain 1445t(T), was isolated from a hot spring on Kunashir Island (Kuril
      Islands, Russia). Cells were motile rods (0.4-0.5 * 1.0-3.0 um). The temperature
      range for growth at pH 7.8 was 46-80  degrees C, with optimum growth at 65 
      degrees C. The pH range for growth at 65  degrees C was pH 5.7-9.0, with optimum
      growth at pH 7.8. Growth was not observed at or below 40  degrees C, at or above
      84  degrees C, at or below pH 5.4 or at or above pH 9.5. The isolate degraded a
      wide range of substrates including starch, cellulose and cellulose derivatives.
      Elemental sulfur stimulated growth, but sodium sulfate, sulfite and thiosulfate
      did not. DNA G+C content was 31 mol%. Phylogenetic analysis of 16S rRNA gene
      sequences showed that strain 1445t(T) belonged to the genus Fervidobacterium. 16S
      rRNA gene sequence similarities with strains of other species of the genus
      Fervidobacterium were 94.9-98.3 %; the type strain of Fervidobacterium
      gondwanense was the closest relative of strain 1445t(T). DNA-DNA hybridization of
      strain 1445t(T) and F. gondwanense AB39(T) revealed a relatedness value of 20 %.
      Based on phylogenetic data and physiological properties of the isolate, a novel
      species, designated Fervidobacterium riparium sp. nov., is proposed with strain
      1445t(T) ( = DSM 21630(T) = VKM B-2549(T)) as the type strain.

PMID- 21169458
TI  - Halobellus clavatus gen. nov., sp. nov. and Halorientalis regularis gen. nov.,
      sp. nov., two new members of the family Halobacteriaceae.
AB  - Four halophilic archaeal strains, designated TNN18(T), TBN12, TNN28(T) and TBN19,
      were isolated from brines sampled from two artificial marine solar salterns in
      eastern China. Strains TNN18(T) and TNN28(T) were isolated from the Tainan marine
      solar saltern, whereas strains TBN12 and TBN19 were from the Taibei marine solar
      saltern. Colonies of the four strains were red-pigmented and their cells were
      pleomorphic, motile, Gram-reaction-negative rods. Strains TNN18(T) and TBN12 were
      able to grow at 25-50  degrees C (optimum 37  degrees C), in 10-3  % (w/v) NaCl
      (optimum 15 %), with 0-1.0 M MgCl(2) (optimum 0.05 M) and at pH 5.5-9.0 (optimum
      pH 7.0-7.5), while strains TNN28(T) and TBN19 were able to grow at 20-50  degrees
      C (optimum 37  degrees C), in 15-30 % (w/v) NaCl (optimum 18-20 %), in 0.005-1.0
      M MgCl(2) (optimum 0.01-0.3 M) and at pH 6.0-9.0 (optimum pH 7.0-7.5). Cells of
      these strains lyse in distilled water; minimal NaCl concentrations to prevent
      cell-lysis are 10 % (w/v) for strains TNN18(T) and TBN12 and 12 % (w/v) for
      strains TNN28(T) and TBN19. The major polar lipids of strains TNN18(T) and TBN12
      were phosphatidylglycerol (PG), phosphatidylglycerol phosphate methyl ester (PGP
      Me), phosphatidylglycerol sulfate (PGS) and one major glycolipid (GL1), which was
      chromatographically identical to sulfated mannosyl glucosyl diether (S-DGD-1).
      Minor amounts of other lipids (GL0, GL2, GL3 and GL4) were also detectable. The
      polar lipid profiles of strains TNN28(T) and TBN19 contained PG, PGP-Me, GL1,
      which was chromatographically identical to S-DGD-1, and three to four minor
      unidentified glycolipids (GL2-GL5). Phylogenetic analyses revealed that strains
      TNN18(T) and TBN12 formed a distinct clade with strains of the closest related
      species, Haloquadratum walsbyi (91.5-91.8 % 16S rRNA gene sequence similarity)
      and strains TNN28(T) and TBN19 formed a distinct clade with strains of the
      species Halosimplex carlsbadense (89.9-93.3 % similarity) and two members of the
      genus Halorhabdus (92.5-93.3 % similarity). The DNA G+C contents of strains
      TNN18(T), TBN12, TNN28(T) and TBN19 were 61.5, 62.4, 61.9 and 61.5 mol%,
      respectively. DNA-DNA hybridization values between strains TNN18(T) and TBN12,
      and strains TNN28(T) and TBN19 were 82.9 % and 88.2 %, respectively. The
      phenotypic, chemotaxonomic and phylogenetic properties suggest that the four
      strains represent two novel species of two new genera within the family
      Halobacteriaceae, for which the names Halobellus clavatus gen. nov., sp. nov.
      (type strain TNN18(T ) = CGMCC 1.10118(T ) = JCM 16424(T)) and Halorientalis
      regularis gen. nov., sp. nov. (type strain TNN28(T ) = CGMCC 1.10123(T ) = JCM
      16425(T)) are proposed.

PMID- 21169459
TI  - Nitratireductor aquimarinus sp. nov., isolated from a culture of the diatom
      Skeletonema costatum, and emended description of the genus Nitratireductor.
AB  - Two Gram-negative-staining, aerobic bacterial strains, designated CL-SC21(T) and
      CL-SC22, were isolated from a culture of the diatom Skeletonema costatum (Korean
      Marine Microalgae Culture Center, KMMCC strain B-396) established from the East
      Sea, Korea. The two novel strains shared 99.9 % 16S rRNA gene sequence
      similarity. Analysis of the 16S rRNA gene sequences showed an affiliation with
      the genus Nitratireductor, with the strains sharing 96.5-97.5 % similarity with
      the type strains of recognized species of the genus Nitratireductor and being
      most closely related to Nitratireductor aquibiodomus NL21(T). Phylogenetic
      analyses of the 16S rRNA gene sequences showed that strain CL-SC21(T) together
      with strain CL-SC22 belonged to the genus Nitratireductor and formed a robust
      clade among closely related Nitratireductor species. The polar lipids comprised
      phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylmonomethylethanolamine, two unidentified
      aminophospholipids, an unidentified aminolipid, an unidentified phospholipid and
      five unidentified lipids. Ubiquinone 10 was the major quinone. The major cellular
      fatty acids of strains CL-SC21(T) and CL-SC22 were C(18 : 1)omega7c (70.6-72.3 %)
      and C(19 : 0)omega8c cyclo (10.9-11.8 %). The genomic DNA G+C contents of strains
      CL-SC21(T) and CL-SC22 were 56.7 and 57.1 mol%, respectively. The level of DNA
      DNA relatedness between strains CL-SC21(T) and CL-SC22 was 86 % (reciprocal 91
      %), indicating that the two isolates represented a single species. However,
      levels of DNA-DNA relatedness between N. aquibiodomus NL21(T) and strains CL
      SC21(T) and CL-SC22 were 28 % (reciprocal 45 %) and 25 % (reciprocal 50 %),
      respectively. Phylogenetic analysis and the results of biochemical tests showed
      that strains CL-SC21(T) and CL-SC22 were different from all recognized species of
      the genus Nitratireductor. Thus, strains CL-SC21(T) and CL-SC22 represent a novel
      species of the genus Nitratireductor, for which the name Nitratireductor
      aquimarinus sp. nov. is proposed. The type strain is CL-SC21(T) ( = KCCM 90090(T)
      = JCM 17288(T)).

PMID- 21169460
TI  - Characterization of two urostylid ciliates, Metaurostylopsis flavicana spec. nov.
      and Tunicothrix wilberti (Lin & Song, 2004) Xu et al., 2006 (Ciliophora,
      Stichotrichia), from a mangrove nature protection area in China.
AB  - Two marine stichotrich ciliates, Metaurostylopsis flavicana spec. nov. and
      Tunicothrix wilberti (Lin & Song, 2004) Xu et al., 2006, isolated from the
      Shenzhen Mangrove Protection Area on the coast of the South China Sea, were
      investigated using live observation and protargol impregnation techniques.
      Metaurostylopsis flavicana is characterized by its elongate body shape, yellowish
      body colour and bright-yellow cortical granules that are either grouped around
      the cirri and the dorsal cilia or aligned between the rows of cirri and dorsal
      cilia. It has four to eight frontal, two frontoterminal, one buccal and seven to
      ten transverse cirri, a mid-ventral complex comprising 13-17 midventral cirral
      pairs in a row that extends about three-fifths of the body length, four left and
      three right marginal rows and three complete dorsal kineties. The small subunit
      rRNA gene of this species was sequenced and phylogenetic trees were constructed
      in which M. flavicana does not group with its congeners, suggesting that the
      genus Metaurostylopsis is paraphyletic. Some supplementary morphological and
      morphogenetic traits for Tunicothrix wilberti are also documented.

PMID- 21169461
TI  - Taxonomy, ontogeny and molecular phylogeny of Anteholosticha marimonilata spec.
      nov. (Ciliophora, Hypotrichida) from the Yellow Sea, China.
AB  - The morphology, morphogenesis and molecular phylogeny of the marine ciliated
      protozoan Anteholosticha marimonilata spec. nov., isolated from mollusc-farming
      waters of the Yellow Sea, Qingdao, PR China, were investigated using microscopic
      observations of live and protargol-impregnated specimens and by small subunit
      rRNA gene sequence analysis. The novel species could be distinguished by the
      following features: an elongated elliptical body, in vivo size 80-160 um * 30-50
      um; an adoral zone consisting of about 36 membranelles; three frontal, one
      parabuccal, one buccal, two frontoterminal and usually two pretransverse ventral
      cirri; 10-13 transverse cirri; a midventral complex composed of 12-17 pairs of
      cirri only, terminating in posterior 1/5; four or five dorsal kineties; two types
      of colourless cortical granules; four to nine moniliform macronuclear nodules and
      one to three micronuclei, and a contractile vacuole positioned at mid-body.
      Hitherto, the ontogenesis of the genus Anteholosticha has been regarded as rather
      diverse, which was confirmed by the morphogenetic processes of this novel
      species. The most noteworthy feature of A. marimonilata was that the proter
      retained almost the entire parental adoral zone except for a few proximal
      membranelles that were renewed in situ. The SSU rRNA gene sequence information
      clearly discriminated this isolate from its congeners. Molecular phylogenetic
      analyses demonstrated, with high statistical support, that A. marimonilata
      branched as a sister lineage to the Nothoholosticha-Pseudokeronopsis clade and
      hence belongs to the core part of the order Urostylida.

PMID- 21169462
TI  - Elizabethkingia anophelis sp. nov., isolated from the midgut of the mosquito
      Anopheles gambiae.
AB  - The taxonomic position, growth characteristics and antibiotic resistance
      properties of a slightly yellow-pigmented bacterial strain, designated R26(T),
      isolated from the midgut of the mosquito Anopheles gambiae, were studied. The
      isolate produced rod-shaped cells, which stained Gram-negative. The bacterium had
      two growth optima at 30-31  degrees C and 37  degrees C. Strain R26(T)
      demonstrated natural antibiotic resistance to ampicillin, chloramphenicol,
      kanamycin, streptomycin and tetracycline. 16S rRNA gene sequence analysis
      revealed that the isolate showed 98.6 % sequence similarity to that of
      Elizabethkingia meningoseptica ATCC 13253(T) and 98.2 % similarity to that of
      Elizabethkingia miricola GTC 862(T). The major fatty acids of strain R26(T) were
      iso-C(15 : 0), iso-C(17 : 0) 3-OH and summed feature 4 (iso-C(15 : 0) 2-OH and/or
      C(16 : 1)omega7c/t). Strain R26(T) contained only menaquinone MK-6 and showed a
      complex polar lipid profile consisting of diphosphatidylglycerol,
      phosphatidylinositol, an unknown phospholipid and unknown polar lipids and
      glycolipids. DNA-DNA hybridization experiments with E. meningoseptica CCUG 214(T)
      ( = ATCC 13253(T)) and E. miricola KCTC 12492(T) ( = GTC 862(T)) gave relatedness
      values of 34.5 % (reciprocal 41.5 %) and 35.0 % (reciprocal 25.7 %),
      respectively. DNA-DNA hybridization results and some differentiating biochemical
      properties indicate that strain R26(T) represents a novel species, for which the
      name Elizabethkingia anophelis sp. nov. is proposed. The type strain is R26(T) (
      = CCUG 60038(T) = CCM 7804(T)).

PMID- 21169463
TI  - Streptomyces indicus sp. nov., an actinomycete isolated from deep-sea sediment.
AB  - The taxonomic position of an actinomycete isolated from deep-sea sediment from
      the Indian Ocean was determined by using a polyphasic approach. The presence of
      iso-C(15 : 0), anteiso-C(15 : 0), iso-C(16 : 0), iso-C(17 : 0) and anteiso-C(17 :
      0) as the major cellular fatty acids, ll-diaminopimelic acid as the
      characteristic diamino acid, and MK-9(H(4), H(6) and H(8)) as the major
      menaquinones supported the affiliation of strain IH32-1(T) to the genus
      Streptomyces. Comparison of 16S rRNA gene sequences showed that strain IH32-1(T)
      exhibited highest similarities to the type strains of Streptomyces globosus (97.6
      %) and Streptomyces toxytricini (97.6 %). However, DNA-DNA relatedness values
      between strain IH32-1(T) and the type strains of S. globosus and S. toxytricini
      were determined as 55.2 +/- 4.7 and 38.3 +/- 2.5 %, respectively. Based on its
      chemotaxonomic, phenotypic and genotypic characteristics, strain IH32-1(T) is
      considered to represent a novel species in the genus Streptomyces, for which the
      name Streptomyces indicus sp. nov. is proposed. The type strain is IH32-1(T) ( =
      DSM 42001(T) = CGMCC 4.5727(T)).

PMID- 21169464
TI  - Williamsia phyllosphaerae sp. nov., isolated from the surface of Trifolium repens
      leaves.
AB  - A Gram-positive-staining, non-endospore-forming actinobacterium, designated
      C7(T), was isolated from the leaf surface of Trifolium repens. On the basis of
      16S rRNA gene sequence analysis, strain C7(T) was shown to belong to the genus
      Williamsia and was most closely related to Williamsia maris SJS0289/JS1(T) (98.0
      % 16S rRNA gene sequence similarity), Williamsia deligens IMMIB RIV-956(T) (96.4
      %) and Williamsia serinedens IMMIB SR-4(T) (95.7 %). The quinone system consisted
      predominantly of the menaquinones MK-9(H(2)), MK-8(H(2)) and MK-7(H(2)). The
      major components in the polar lipid profile were diphosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylglycerol and phosphatidylinositol. Mycolic
      acids were present. These chemotaxonomic traits and the major fatty acids, which
      were C(16 : 1)omega7c, C(16 : 0), C(18 : 0), C(18 : 1)omega9c and
      tuberculostearic acid, supported the affiliation of strain C7(T) with the genus
      Williamsia. Physiological and biochemical analysis revealed clear differences
      between strain C7(T) and its closest phylogenetic neighbours. Therefore, strain
      C7(T) represents a novel species, for which the name Williamsia phyllosphaerae
      sp. nov. is proposed. The type strain is C7(T) ( = CCUG 60465(T) = CCM 7855(T)).

PMID- 21169465
TI  - Desulfovibrio piezophilus sp. nov., a piezophilic, sulfate-reducing bacterium
      isolated from wood falls in the Mediterranean Sea.
AB  - A novel sulfate-reducing bacterium, designated C1TLV30(T), was isolated from wood
      falls at a depth of 1693 m in the Mediterranean Sea. Cells were motile vibrios (2
      4 * 0.5 um). Strain C1TLV30(T) grew at temperatures between 15 and 45  degrees C
      (optimum 30  degrees C) and at pH 5.4-8.6 (optimum 7.3). It required NaCl for
      growth (optimum at 25 g NaCl l(-1)) and tolerated up to 80 g NaCl l(-1). Strain
      C1TLV30(T) used as energy sources: lactate, fumarate, formate, malate, pyruvate
      and ethanol. The end products from lactate oxidation were acetate, H(2)S and
      CO(2) in the presence of sulfate as terminal electron acceptor. Besides sulfate,
      thiosulfate and sulfite were also used as terminal electron acceptors, but not
      elemental sulfur, fumarate, nitrate or nitrite. Strain C1TLV30(T) possessed
      desulfoviridin and was piezophilic, growing optimally at 10 MPa (range 0-30 MPa).
      The membrane lipid composition of this strain was examined to reveal an increase
      in fatty acid chain lengths at high hydrostatic pressures. The G+C content of the
      genomic DNA was 49.6 % and the genome size was estimated at 3.5 +/- 0.5 Mb.
      Phylogenetic analysis of the SSU rRNA gene sequence indicated that strain
      C1TLV30(T) was affiliated to the genus Desulfovibrio with Desulfovibrio profundus
      being its closest phylogenetic relative (similarity of 96.4 %). On the basis of
      SSU rRNA gene sequence comparisons and physiological characteristics, strain
      C1TLV30(T) ( = DSM 21447(T) = JCM 1548(T)) is proposed to be assigned to a novel
      species of the genus Desulfovibrio, Desulfovibrio piezophilus sp. nov.

PMID- 21169466
TI  - Addressing the complexity of chronic obstructive pulmonary disease: from
      phenotypes and biomarkers to scale-free networks, systems biology, and P4
      medicine.
AB  - Chronic obstructive pulmonary disease (COPD) is a complex disease at the
      clinical, cellular, and molecular levels. However, its diagnosis, assessment, and
      therapeutic management are based almost exclusively on the severity of airflow
      limitation. A better understanding of the multiple dimensions of COPD and its
      relationship to other diseases is very relevant and of high current interest.
      Recent theoretical (scale-free networks), technological (high-throughput
      technology, biocomputing), and analytical improvements (systems biology) provide
      tools capable of addressing the complexity of COPD. The information obtained from
      the integrated use of those techniques will be eventually incorporated into
      routine clinical practice. This review summarizes our current knowledge in this
      area and offers an insight into the elements needed to progress toward an
      integrated, multilevel view of COPD based on the novel scientific strategy of
      systems biology and its potential clinical derivative, P4 medicine (Personalized,
      Predictive, Preventive, and Participatory).

PMID- 21169467
TI  - Relationship between group-specific component protein and the development of
      asthma.
AB  - RATIONALE: Airway inflammation and remodeling during asthma are attributed to the
      altered expression of biologically relevant proteins. OBJECTIVES: To search for
      asthma-specific proteins in bronchoalveolar lavage fluid (BAL) from individuals
      with asthma and to validate the identified proteins in an experimental model of
      asthma. METHODS: Liquid chromatography-tandem mass spectrometry was performed to
      identify proteins in BAL fluid found by two dimensional electrophoresis (2DE) to
      be differentially expressed in subjects with asthma versus control subjects.
      Group-specific component (Gc) and mRNA levels were measured using an ELISA,
      Western blots, and PCR. A neutralization study using an antibody against Gc
      protein was performed in an experimental asthma model. MEASUREMENTS AND MAIN
      RESULTS: Based on 2DE, 15 proteins were significantly up-regulated or down
      regulated in eight subjects with asthma compared with eight control subjects. The
      protein levels of Gc, hemopexin, and haptoglobin-b were increased, whereas the a1
      antitrypsin and glutathione S-transferase levels were decreased in subjects with
      asthma. The Gc concentration in BAL fluid was significantly elevated in 67
      subjects with asthma compared with that in 22 control subjects (P < 0.009). The
      Gc was significantly correlated with the neutrophil percentage in BAL fluid of
      subjects with asthma (P = 0.001). Gc mRNA and protein levels were higher in
      ovalbumin-sensitized/ challenged asthma mice than in sham-treated mice. Gc
      protein were expressed on alveolar macrophages and on epithelial cells. Treatment
      with an anti-Gc antibody dose-dependently reduced the ovalbumin
      sensitization/challenge-induced enhancement of airway hyperreactivity, airway
      inflammation, goblet cell hyperplasia,and levels of eotaxin, interleukin-4, -5,
      and -13, and interferon-g. CONCLUSIONS: Gc may be involved in the development of
      asthma, and the neutralization of Gc protein could be a therapeutic strategy for
      asthma.

PMID- 21169468
TI  - Mesenchymal stromal cells in bronchoalveolar lavage as predictors of
      bronchiolitis obliterans syndrome.
AB  - RATIONALE: Bronchoalveolar lavage fluid (BAL) from human lung allografts
      demonstrates the presence of a multipotent mesenchymal stromal cell population.
      However, the clinical relevance of this novel cellular component of BAL and its
      association with bronchiolitis obliterans syndrome (BOS), a disease marked by
      progressive airflow limitation secondary to fibrotic obliteration of the small
      airways, remains to be determined. OBJECTIVES: In this study we investigate the
      association of number of mesenchymal stromal cells in BAL with development of BOS
      in human lung transplant recipients. METHODS: Mesenchymal colony-forming units
      (CFUs) were quantitated in a cohort of 405 BAL samples obtained from 162 lung
      transplant recipients. Poisson generalized estimating equations were used to
      determine the predictors of BAL mesenchymal CFU count. MEASUREMENTS AND MAIN
      RESULTS: Higher CFU counts were noted early post-transplantation; time from
      transplant to BAL of greater than 3 months predicted 0.4-fold lower CFU counts (P
      = 0.0001). BOS diagnosis less than or equal to 365 days before BAL was associated
      with a 2.11-fold higher CFU count (P = 0.02). There were 2.62- and 2.70-fold
      higher CFU counts noted in the presence of histologic diagnosis of bronchiolitis
      obliterans (P = 0.05) and organizing pneumonia (0.0003), respectively. In BAL
      samples obtained from BOS-free patients greater than 6 months post
      transplantation (n = 173), higher mesenchymal CFU counts (>=10) significantly
      predicted BOS onset in both univariate (hazard ratio, 5.61; 95% CI, 3.03-10.38; P
      < 0.0001) and multivariate (hazard ratio, 5.02; 95% CI, 2.40-10.51; P < 0.0001)
      Cox regression analysis. CONCLUSIONS: Measurement of mesenchymal CFUs in the BAL
      provides predictive information regarding future BOS onset.

PMID- 21169469
TI  - Yin yang 1 is a novel regulator of pulmonary fibrosis.
AB  - RATIONALE: The differentiation of fibroblasts into myofibroblasts is a cardinal
      feature of idiopathic pulmonary fibrosis (IPF). The transcription factor Yin Yang
      1 (YY1) plays a role in the proliferation and differentiation of diverse cell
      types, but its role in fibrotic lung diseases is not known. OBJECTIVES: To
      elucidate the mechanism by which YY1 regulates fibroblast differentiation and
      lung fibrosis. METHODS: Lung fibroblasts were cultured with transforming growth
      factor (TGF)-beta or tumor necrosis factor-alpha. Nuclear factor (NF)-kappaB,
      YY1, and alpha-smooth muscle actin (SMA) were determined in protein, mRNA, and
      promoter reporter level. Lung fibroblasts and lung fibrosis were assessed in a
      partial YY1-deficient mouse and a YY1(f/f) conditional knockout mouse after being
      exposed to silica or bleomycin. MEASUREMENTS AND MAIN RESULTS: TGF-beta and tumor
      necrosis factor-alpha up-regulated YY1 expression in lung fibroblasts. TGF-beta
      induced YY1 expression was dramatically decreased by an inhibitor of NF-kappaB,
      which blocked I-kappaB degradation. YY1 is significantly overexpressed in both
      human IPF and murine models of lung fibrosis, including in the aggregated
      pulmonary fibroblasts of fibrotic foci. Furthermore, the mechanism of
      fibrogenesis is that YY1 can up-regulate alpha-SMA expression in pulmonary
      fibroblasts. YY1-deficient (YY1(+/-)) mice were significantly protected from lung
      fibrosis, which was associated with attenuated alpha-SMA and collagen expression.
      Finally, decreasing YY1 expression through instilled adenovirus-cre in floxed
      YY1(f/f) mice reduced lung fibrosis. CONCLUSIONS: YY1 is overexpressed in
      fibroblasts in both human IPF and murine models in a NF-kappaB-dependent manner,
      and YY1 regulates fibrogenesis at least in part by increasing alpha-SMA and
      collagen expression. Decreasing YY1 expression may provide a new therapeutic
      strategy for pulmonary fibrosis.

PMID- 21169470
TI  - Interferon-gamma production by neutrophils during bacterial pneumonia in mice.
AB  - RATIONALE: Neutrophils are usually the first circulating leukocytes to respond
      during bacterial pneumonia. Their expression of oxidants, proteases, and other
      mediators present in granules is well documented, but their ability to produce
      mediators through transcription and translation after migration to an
      inflammatory site has been appreciated only more recently. Interferon (IFN)-gamma
      is a cytokine with many functions important in host defense and immunity.
      OBJECTIVES: To examine the expression and function of IFN-gamma in bacterial
      pneumonias. METHODS: IFN-gamma mRNA and protein were measured in digests of mouse
      lungs with 24-hour bacterial pneumonia. Bacterial clearance was studied with IFN
      gamma-deficient mice. MEASUREMENTS AND MAIN RESULTS: Streptococcus pneumoniae and
      Staphylococcus aureus each induce expression of IFN-gamma mRNA and protein by
      neutrophils by 24 hours. Only neutrophils that have migrated into pneumonic
      tissue produce IFN-gamma. Deficiency of Hck/Fgr/Lyn, Rac2, or gp91(phox) prevents
      IFN-gamma production. IFN-gamma enhances bacterial clearance and is required for
      formation of neutrophil extracellular traps. In contrast, Pseudomonas aeruginosa
      and Escherichia coli induce production of IFN-gamma mRNA but not protein. During
      pneumonia induced by E. coli but not S. pneumoniae, neutrophils produce microRNAs
      that target the 3' untranslated region of the IFN-gamma gene. CONCLUSIONS: S.
      pneumoniae and S. aureus, but not P. aeruginosa and E. coli, induce emigrated
      neutrophils to produce IFN-gamma within 24 hours. Hck/Fgr/Lyn, Rac2, and NADPH
      oxidase are required for IFN-gamma production. IFN-gamma facilitates bacterial
      clearance at least in part through regulating formation of neutrophil
      extracellular traps. Differential expression by neutrophils of microRNAs that
      target the 3' untranslated region of the IFN-gamma gene may contribute to the
      pathogen-specific regulation of translation.

PMID- 21169473
TI  - Different types of K-Ras mutations could affect drug sensitivity and tumour
      behaviour in non-small-cell lung cancer.

PMID- 21169474
TI  - Control of carcinoid syndrome with everolimus.

PMID- 21169475
TI  - Capecitabine combined with oxaliplatin (CAPOX) in clinical practice: how
      significant is peripheral neuropathy?

PMID- 21169471
TI  - Denufosol tetrasodium in patients with cystic fibrosis and normal to mildly
      impaired lung function.
AB  - RATIONALE: Intervention for cystic fibrosis lung disease early in its course has
      the potential to delay or prevent progressive changes that lead to irreversible
      airflow obstruction. Denufosol is a novel ion channel regulator designed to
      correct the ion transport defect and increase the overall mucociliary clearance
      in cystic fibrosis lung disease by increasing chloride secretion, inhibiting
      sodium absorption, and increasing ciliary beat frequency in the airway epithelium
      independently of cystic fibrosis transmembrane conductance regulator genotype.
      OBJECTIVES: To evaluate the efficacy and safety of denufosol in patients with
      cystic fibrosis who had normal to mildly impaired lung function characteristic of
      early cystic fibrosis. METHODS: A total of 352 patients greater than or equal to
      5 years old with cystic fibrosis who had FEV(1) greater than or equal to 75% of
      predicted normal were randomized to receive inhaled denufosol, 60 mg, or placebo
      three times daily in a Phase 3, randomized, double-blind, placebo-controlled, 24
      week trial. MEASUREMENTS AND MAIN RESULTS: Main outcome measures included change
      in FEV(1) from baseline to Week 24 endpoint and adverse events. Mean change from
      baseline to Week 24 endpoint in FEV(1) (primary efficacy endpoint) was 0.048 L
      for denufosol (n = 178) and 0.003 L for placebo (n = 174; P = 0.047). No
      significant differences between groups were observed for secondary endpoints
      including exacerbation rate and other measures of lung function. Denufosol was
      well tolerated with adverse event and growth profiles similar to placebo.
      CONCLUSIONS: Denufosol improved lung function relative to placebo in cystic
      fibrosis patients with normal to mildly impaired lung function. Clinical trial
      registered with www.clinicaltrials.gov (NCT00357279).

PMID- 21169477
TI  - Social relationships in religious institutions and healthy lifestyles.
AB  - The purpose of this study is to see if encouragement from fellow church members
      helps older people develop and maintain healthy lifestyles. The findings indicate
      that informal church-based support is associated with healthy lifestyles among
      older African Americans but not older Whites. In addition, the influence of
      support from fellow church members on health behaviors is greater for study
      participants who closely identify with their congregations. The results further
      reveal that the adoption of healthy lifestyles is not associated with support
      from people outside the church nor is it linked to formal programs that churches
      provide to encourage good health behaviors. The theoretical and practice
      implications of these results are discussed.

PMID- 21169478
TI  - Exploring community health through the Sustainable Livelihoods framework.
AB  - Health disparities are a major concern in the United States. Research suggests
      that inequitable distribution of money, power, and resources shape the
      circumstances for daily life and create and exacerbate health disparities. In
      rural communities, inequitable distribution of these structural factors seems to
      limit employment opportunities. The Sustainable Livelihoods framework, an
      economic development model, provides a conceptual framework to understand how
      distribution of these social, economic, and political structural factors affect
      employment opportunities and community health in rural America. This study uses
      photo-elicitation interviews, a qualitative, participatory method, to understand
      community members' perceptions of how distribution of structural factors through
      creation and maintenance of institutional practices and policies influence
      employment opportunities and, ultimately, community health for African Americans
      living in rural Missouri.

PMID- 21169479
TI  - Obesity and body size preferences of Jordanian women.
AB  - The nutrition transition is associated with increased obesity rates and increased
      desire to be thin. This study evaluates the relationship between actual body size
      and desired body size among a representative sample of 800 Jordanian women. Using
      Stunkard's body silhouettes, women were asked to identify their current and ideal
      body sizes, healthy body size, and their perception of the body size preferred by
      men. Body mass index (BMI) calculations indicate that 53.8% of the women were
      overweight or obese. Their mean current body size was 5, which is consistent with
      the mean BMI of 26 in the sample. Although 66% of the women were dissatisfied
      with their body size, the desired weight loss was not extreme. Pearson
      correlation was positive (.858, p <.0001) between measured BMI and body
      silhouettes chosen as an indicator of current body size. Jordanian women seemed
      pulled between the traditional and Westernized body preferences. Possible
      cultural explanations are explored.

PMID- 21169480
TI  - miR-ID: a novel, circularization-based platform for detection of microRNAs.
AB  - MicroRNAs (miRNAs) are important regulators of gene expression and have great
      potential as biomarkers, prognostic indicators, and therapeutic targets.
      Determining the expression patterns of these molecules is essential for
      elucidating their biogenesis, regulation, relation to disease, and response to
      therapy. Although PCR-based assays are commonly used for expression profiling of
      miRNAs, the small size, sequence heterogeneity, and (in some cases) end
      modifications of miRNAs constrain the performance of existing PCR methods. Here
      we introduce miR-ID, a novel method that avoids these constraints while providing
      superior sensitivity and sequence specificity at a lower cost. It also has the
      unique ability to differentiate unmodified small RNAs from those carrying 2'-OMe
      groups at their 3'-ends while detecting both forms. miR-ID is comprised of the
      following steps: (1) circularization of the miRNA by a ligase; (2) reverse
      transcription of the circularized miRNA (RTC), producing tandem repeats of a DNA
      sequence complementary to the miRNA; and (3) qPCR amplification of segments of
      this multimeric cDNA using 5'-overlapping primers and a nonspecific dye such as
      SYBR Green. No chemically modified probes (e.g., TaqMan) or primers (e.g., LNA)
      are required. The circular RNA and multimeric cDNA templates provide unmatched
      flexibility in the positioning of primers, which may include straddling the
      boundaries between these repetitive miRNA sequences. miR-ID is based on new
      findings that are themselves of general interest, including reverse transcription
      of small RNA circles and the use of 5'-overlapping primers for detection of
      repetitive sequences by qPCR.

PMID- 21169481
TI  - Antibiotics and UV radiation induce competence for natural transformation in
      Legionella pneumophila.
AB  - Natural transformation by competence is a major mechanism of horizontal gene
      transfer in bacteria. Competence is defined as the genetically programmed
      physiological state that enables bacteria to actively take up DNA from the
      environment. The conditions that signal competence development are multiple and
      elusive, complicating the understanding of its evolutionary significance. We used
      expression of the competence gene comEA as a reporter of competence development
      and screened several hundred molecules for their ability to induce competence in
      the freshwater living pathogen Legionella pneumophila. We found that comEA
      expression is induced by chronic exposure to genotoxic molecules such as
      mitomycin C and antibiotics of the fluoroquinolone family. These results
      indicated that, in L. pneumophila, competence may be a response to genotoxic
      stress. Sunlight-emitted UV light represents a major source of genotoxic stress
      in the environment and we found that exposure to UV radiation effectively induces
      competence development. For the first time, we show that genetic exchanges by
      natural transformation occur within an UV-stressed population. Genotoxic stress
      induces the RecA-dependent SOS response in many bacteria. However, genetic and
      phenotypic evidence suggest that L. pneumophila lacks a prototypic SOS response
      and competence development in response to genotoxic stress is RecA independent.
      Our results strengthen the hypothesis that competence may have evolved as a DNA
      damage response in SOS-deficient bacteria. This parasexual response to DNA damage
      may have enabled L. pneumophila to acquire and propagate foreign genes,
      contributing to the emergence of this human pathogen.

PMID- 21169482
TI  - Identification of missing genes and enzymes for autotrophic carbon fixation in
      crenarchaeota.
AB  - Two autotrophic carbon fixation cycles have been identified in Crenarchaeota. The
      dicarboxylate/4-hydroxybutyrate cycle functions in anaerobic or microaerobic
      autotrophic members of the Thermoproteales and Desulfurococcales. The 3
      hydroxypropionate/4-hydroxybutyrate cycle occurs in aerobic autotrophic
      Sulfolobales; a similar cycle may operate in autotrophic aerobic marine
      Crenarchaeota. Both cycles form succinyl-coenzyme A (CoA) from acetyl-CoA and two
      molecules of inorganic carbon, but they use different means. Both cycles have in
      common the (re)generation of acetyl-CoA from succinyl-CoA via identical
      intermediates. Here, we identified several missing enzymes/genes involved in the
      seven-step conversion of succinyl-CoA to two molecules of acetyl-CoA in
      Thermoproteus neutrophilus (Thermoproteales), Ignicoccus hospitalis
      (Desulfurococcales), and Metallosphaera sedula (Sulfolobales). The identified
      enzymes/genes include succinyl-CoA reductase, succinic semialdehyde reductase, 4
      hydroxybutyrate-CoA ligase, bifunctional crotonyl-CoA hydratase/(S)-3
      hydroxybutyryl-CoA dehydrogenase, and beta-ketothiolase. 4-Hydroxybutyryl-CoA
      dehydratase, which catalyzes a mechanistically intriguing elimination of water,
      is well conserved and rightly can be considered the key enzyme of these two
      cycles. In contrast, several of the other enzymes evolved from quite different
      sources, making functional predictions based solely on genome interpretation
      difficult, if not questionable.

PMID- 21169483
TI  - Unexpected coregulator range for the global regulator Lrp of Escherichia coli and
      Proteus mirabilis.
AB  - The Lrp/AsnC family of transcription factors links gene regulation to metabolism
      in bacteria and archaea. Members of this family, collectively, respond to a wide
      range of amino acids as coregulators. In Escherichia coli, Lrp regulates over 200
      genes directly and is well known to respond to leucine and, to a somewhat lesser
      extent, alanine. We focused on Lrp from Proteus mirabilis and E. coli, orthologs
      with 98% identity overall and identical helix-turn-helix motifs, for which a
      previous study nevertheless found functional differences. Sequence differences
      between these orthologs, within and adjacent to the amino acid-responsive RAM
      domain, led us to test for differential sensitivity to coregulatory amino acids.
      In the course of this investigation, we found, via in vivo reporter fusion assays
      and in vitro electrophoretic mobility shift experiments, that E. coli Lrp itself
      responded to a broader range of amino acids than was previously appreciated. In
      particular, for both the E. coli and P. mirabilis orthologs, Lrp responsiveness
      to methionine was similar in magnitude to that to leucine. Both Lrp orthologs are
      also fairly sensitive to Ile, His, and Thr. These observations suggest that Lrp
      ties gene expression in the Enterobacteriaceae rather extensively to
      physiological status, as reflected in amino acid pools. These findings also have
      substantial implications for attempts to model regulatory architecture from
      transcriptome measurements or to infer such architecture from genome sequences,
      and they suggest that even well-studied regulators deserve ongoing exploration.

PMID- 21169485
TI  - New insights into the Lpt machinery for lipopolysaccharide transport to the cell
      surface: LptA-LptC interaction and LptA stability as sensors of a properly
      assembled transenvelope complex.
AB  - Lipopolysaccharide (LPS) is a major glycolipid present in the outer membrane (OM)
      of Gram-negative bacteria. The peculiar permeability barrier of the OM is due to
      the presence of LPS at the outer leaflet of this membrane that prevents many
      toxic compounds from entering the cell. In Escherichia coli LPS synthesized
      inside the cell is first translocated over the inner membrane (IM) by the
      essential MsbA flippase; then, seven essential Lpt proteins located in the IM
      (LptBCDF), in the periplasm (LptA), and in the OM (LptDE) are responsible for LPS
      transport across the periplasmic space and its assembly at the cell surface. The
      Lpt proteins constitute a transenvelope complex spanning IM and OM that appears
      to operate as a single device. We show here that in vivo LptA and LptC physically
      interact, forming a stable complex and, based on the analysis of loss-of-function
      mutations in LptC, we suggest that the C-terminal region of LptC is implicated in
      LptA binding. Moreover, we show that defects in Lpt components of either IM or OM
      result in LptA degradation; thus, LptA abundance in the cell appears to be a
      marker of properly bridged IM and OM. Collectively, our data support the recently
      proposed transenvelope model for LPS transport.

PMID- 21169484
TI  - Requirement of the agr locus for colony spreading of Staphylococcus aureus.
AB  - The important human pathogen Staphylococcus aureus is known to spread on soft
      agar plates. Here, we show that colony spreading of S. aureus involves the agr
      quorum-sensing system. This finding can be related to the agr-dependent
      expression of biosurfactants, such as phenol-soluble modulins, suggesting a
      connection between spreading motility and virulence.

PMID- 21169486
TI  - Labeling and enzyme studies of the central carbon metabolism in Metallosphaera
      sedula.
AB  - Metallosphaera sedula (Sulfolobales, Crenarchaeota) uses the 3
      hydroxypropionate/4-hydroxybutyrate cycle for autotrophic carbon fixation. In
      this pathway, acetyl-coenzyme A (CoA) and succinyl-CoA are the only intermediates
      that can be considered common to the central carbon metabolism. We addressed the
      question of which intermediate of the cycle most biosynthetic routes branch off.
      We labeled autotrophically growing cells by using 4-hydroxy[1-14C]butyrate and
      [1,4-13C1]succinate, respectively, as precursors for biosynthesis. The labeling
      patterns of protein-derived amino acids verified the operation of the proposed
      carbon fixation cycle, in which 4-hydroxybutyrate is converted to two molecules
      of acetyl-CoA. The results also showed that major biosynthetic flux does not
      occur via acetyl-CoA, except for the formation of building blocks that are
      directly derived from acetyl-CoA. Notably, acetyl-CoA is not assimilated via
      reductive carboxylation to pyruvate. Rather, our data suggest that the majority
      of anabolic precursors are derived from succinyl-CoA, which is removed from the
      cycle via oxidation to malate and oxaloacetate. These C4intermediates yield
      pyruvate and phosphoenolpyruvate (PEP). Enzyme activities that are required for
      forming intermediates from succinyl-CoA were detected, including enzymes
      catalyzing gluconeogenesis from PEP. This study completes the picture of the
      central carbon metabolism in autotrophic Sulfolobales by connecting the
      autotrophic carbon fixation cycle to the formation of central carbon precursor
      metabolites.

PMID- 21169487
TI  - Identification of an extracellular polysaccharide network essential for
      cytochrome anchoring and biofilm formation in Geobacter sulfurreducens.
AB  - Transposon insertions in Geobacter sulfurreducens GSU1501, part of an ATP
      dependent exporter within an operon of polysaccharide biosynthesis genes, were
      previously shown to eliminate insoluble Fe(III) reduction and use of an electrode
      as an electron acceptor. Replacement of GSU1501 with a kanamycin resistance
      cassette produced a similarly defective mutant, which could be partially
      complemented by expression of GSU1500 to GSU1505 in trans. The Delta1501 mutant
      demonstrated limited cell-cell agglutination, enhanced attachment to negatively
      charged surfaces, and poor attachment to positively charged poly-d-lysine- or
      Fe(III)-coated surfaces. Wild-type and mutant cells attached to graphite
      electrodes, but when electrodes were poised at an oxidizing potential inducing a
      positive surface charge (+0.24 V versus the standard hydrogen electrode [SHE]),
      Delta1501 mutant cells detached. Scanning electron microscopy revealed fibrils
      surrounding wild-type G. sulfurreducens which were absent from the Delta1501
      mutant. Similar amounts of type IV pili and pilus-associated cytochromes were
      detected on both cell types, but shearing released a stable matrix of c-type
      cytochromes and other proteins bound to polysaccharides. The matrix from the
      mutant contained 60% less sugar and was nearly devoid of c-type cytochromes such
      as OmcZ. The addition of wild-type extracellular matrix to Delta1501 cultures
      restored agglutination and Fe(III) reduction. The polysaccharide binding dye
      Congo red preferentially bound wild-type cells and extracellular matrix material
      over mutant cells, and Congo red inhibited agglutination and Fe(III) reduction by
      wild-type cells. These results demonstrate a crucial role for the xap
      (extracellular anchoring polysaccharide) locus in metal oxide attachment, cell
      cell agglutination, and localization of essential cytochromes beyond the
      Geobacter outer membrane.

PMID- 21169488
TI  - The sensor kinase CbrA is a global regulator that modulates metabolism,
      virulence, and antibiotic resistance in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that possesses a large
      arsenal of virulence factors enabling the pathogen to cause serious infections in
      immunocompromised patients, burn victims, and cystic fibrosis patients. CbrA is a
      sensor kinase that has previously been implied to play a role with its cognate
      response regulator CbrB in the metabolic regulation of carbon and nitrogen
      utilization in P. aeruginosa. Here it is demonstrated that CbrA and CbrB play an
      important role in various virulence and virulence-related processes of the
      bacteria, including swarming, biofilm formation, cytotoxicity, and antibiotic
      resistance. The cbrA deletion mutant was completely unable to swarm while
      exhibiting an increase in biofilm formation, supporting the inverse regulation of
      swarming and biofilm formation in P. aeruginosa. The cbrA mutant also exhibited
      increased cytotoxicity to human lung epithelial cells as early as 4 and 6 h
      postinfection. Furthermore, the cbrA mutant demonstrated increased resistance
      toward a variety of clinically important antibiotics, including polymyxin B,
      ciprofloxacin, and tobramycin. Microarray analysis revealed that under swarming
      conditions, CbrA regulated the expression of many genes, including phoPQ, pmrAB,
      arnBCADTEF, dnaK, and pvdQ, consistent with the antibiotic resistance and
      swarming impairment phenotypes of the cbrA mutant. Phenotypic and real-time
      quantitative PCR (RT-qPCR) analyses of a PA14 cbrB mutant suggested that CbrA may
      be modulating swarming, biofilm formation, and cytotoxicity via CbrB and that the
      CrcZ small RNA is likely downstream of this two-component regulator. However, as
      CbrB did not have a resistance phenotype, CbrA likely modulates antibiotic
      resistance in a manner independent of CbrB.

PMID- 21169489
TI  - Inerolysin, a cholesterol-dependent cytolysin produced by Lactobacillus iners.
AB  - Lactobacillus iners is a common constituent of the human vaginal microbiota. This
      species was only recently characterized due to its fastidious growth requirements
      and has been hypothesized to play a role in the pathogenesis of bacterial
      vaginosis. Here we present the identification and molecular characterization of a
      protein toxin produced by L. iners. The L. iners genome encodes an open reading
      frame with significant primary sequence similarity to intermedilysin (ILY; 69.2%
      similarity) and vaginolysin (VLY; 68.4% similarity), the cholesterol-dependent
      cytolysins from Streptococcus intermedius and Gardnerella vaginalis,
      respectively. Clinical isolates of L. iners produce this protein, inerolysin
      (INY), during growth in vitro, as assessed by Western analysis. INY is a pore
      forming toxin that is activated by reducing agents and inhibited by excess
      cholesterol. It is active across a pH range of 4.5 to 6.0 but is inactive at pH
      7.4. At sublytic concentrations, INY activates p38 mitogen-activated protein
      kinase and allows entry of fluorescent phalloidin into the cytoplasm of
      epithelial cells. Unlike VLY and ILY, which are human specific, INY is active
      against cells from a broad range of species. INY represents a new target for
      studies directed at understanding the role of L. iners in states of health and
      disease at the vaginal mucosal surface.

PMID- 21169490
TI  - A novel cdsAB operon is involved in the uptake of L-cysteine and participates in
      the pathogenesis of Yersinia ruckeri.
AB  - Application of in vivo expression technology (IVET) to Yersinia ruckeri, an
      important fish pathogen, allowed the identification of two adjacent genes that
      represent a novel bacterial system involved in the uptake and degradation of l
      cysteine. Analysis of the translational products of both genes showed permease
      domains (open reading frame 1 [ORF1]) and amino acid position identities (ORF2)
      with the l-cysteine desulfidase from Methanocaldococcus jannaschii, a new type of
      enzyme involved in the breakdown of l-cysteine. The operon was named cdsAB
      (cysteine desulfidase) and is found widely in anaerobic and facultative bacteria.
      cdsAB promoter analysis using lacZY gene fusion showed highest induction in the
      presence of l-cysteine. Two cdsA and cdsB mutant strains were generated. The
      limited toxic effect and the low utilization of l-cysteine observed in the cdsA
      mutant, together with radiolabeled experiments, strongly suggested that CdsA is
      an l-cysteine permease. Fifty percent lethal dose (LD(50)) and competence index
      experiments showed that both the cdsA and cdsB loci were involved in the
      pathogenesis of the bacteria. In conclusion, this study has shown for the first
      time in bacteria the existence of an l-cysteine uptake system that together with
      an additional l-cysteine desulfidase-encoding gene constitutes a novel operon
      involved in bacterial virulence.

PMID- 21169491
TI  - Pyruvate formate lyase acts as a formate supplier for metabolic processes during
      anaerobiosis in Staphylococcus aureus.
AB  - Previous studies demonstrated an upregulation of pyruvate formate lyase (Pfl) and
      NAD-dependent formate dehydrogenase (Fdh) in Staphylococcus aureus biofilms. To
      investigate their physiological role, we constructed fdh and pfl deletion mutants
      (Deltafdh and Deltapfl). Although formate dehydrogenase activity in the fdh
      mutant was lost, it showed little phenotypic alterations under oxygen-limited
      conditions. In contrast, the pfl mutant displayed pleiotropic effects and
      revealed the importance of formate production for anabolic metabolism. In the pfl
      mutant, no formate was produced, glucose consumption was delayed, and ethanol
      production was decreased, whereas acetate and lactate production were unaffected.
      All metabolic alterations could be restored by addition of formate or
      complementation of the Deltapfl mutant. In compensation reactions, serine and
      threonine were consumed better by the Deltapfl mutant than by the wild type,
      suggesting that their catabolism contributes to the refilling of formyl
      tetrahydrofolate, which acts as a donor of formyl groups in, e.g., purine and
      protein biosynthesis. This notion was supported by reduced production of
      formylated peptides by the Deltapfl mutant compared to that of the parental
      strain, as demonstrated by weaker formyl-peptide receptor 1 (FPR1)-mediated
      activation of leukocytes with the mutant. FPR1 stimulation could also be restored
      either by addition of formate or by complementation of the mutation. Furthermore,
      arginine consumption and arc operon transcription were increased in the Deltapfl
      mutant. Unlike what occurred with the investigated anaerobic conditions, a
      biofilm is distinguished by nutrient, oxygen, and pH gradients, and we thus
      assume that Pfl plays a significant role in the anaerobic layer of a biofilm. Fdh
      might be critical in (micro)aerobic layers, as formate oxidation is correlated
      with the generation of NADH/H(+), whose regeneration requires respiration.

PMID- 21169492
TI  - H-NS binding and repression of the ctx promoter in Vibrio cholerae.
AB  - Expression of the ctx and tcp genes, which encode cholera toxin and the toxin
      coregulated pilus, the Vibrio cholerae O1 virulence determinants having the
      largest contribution to cholera disease, is repressed by the nucleoid-associated
      protein H-NS and activated by the AraC-like transcriptional regulator ToxT. To
      elucidate the molecular mechanism by which H-NS controls transcription of the
      ctxAB operon, H-NS repression and binding were characterized by using a promoter
      truncation series, gel mobility shift assays, and DNase I footprinting. Promoter
      regions found to be important for H-NS repression correlated with in vitro
      binding. Four main H-NS binding regions are present at ctx. One region overlaps
      the high-affinity ToxT binding site and extends upstream, another overlaps the
      ToxT low-affinity binding site around the -35 element, and the remaining two are
      located adjacent to one another downstream of the transcriptional start site.
      Competition for binding to the overlapping H-NS/ToxT binding sites was observed
      in gel mobility shift assays, where ToxT was found to displace H-NS from the ctx
      promoter region. In addition, regulatory differences between the ctx and tcpA
      promoters were examined. H-NS was found to have a higher relative binding
      affinity for the ctx promoter than for the tcpA promoter in vitro. In contrast to
      ToxT-dependent activation of the tcpA promoter, ToxT activation of ctx did not
      require the C-terminal domain of the alpha-subunit of RNA polymerase. These
      findings demonstrate that transcriptional regulation of ctx and tcpA by H-NS and
      ToxT is mechanistically distinct, and this may lead to important differences in
      the expression of these coregulated genes.

PMID- 21169493
TI  - SigG does not control gene expression in response to DNA damage in Mycobacterium
      tuberculosis H37Rv.
AB  - Expression of the Mycobacterium tuberculosis sigG sigma factor was induced by a
      variety of DNA-damaging agents, but inactivation of sigG did not affect induction
      of gene expression or bacterial survival under these conditions. Therefore, SigG
      does not control the DNA repair response of M. tuberculosis H37Rv.

PMID- 21169494
TI  - Identification of two feruloyl esterases in Dickeya dadantii 3937 and induction
      of the major feruloyl esterase and of pectate lyases by ferulic acid.
AB  - The plant-pathogenic bacterium Dickeya dadantii (formerly Erwinia chrysanthemi)
      produces a large array of plant cell wall-degrading enzymes. Using an in situ
      detection test, we showed that it produces two feruloyl esterases, FaeD and FaeT.
      These enzymes cleave the ester link between ferulate and the pectic or xylan
      chains. FaeD and FaeT belong to the carbohydrate esterase family CE10, and they
      are the first two feruloyl esterases to be identified in this family. Cleavage of
      synthetic substrates revealed strong activation of FaeD and FaeT by ferulic acid.
      The gene faeT appeared to be weakly expressed, and its product, FaeT, is a
      cytoplasmic protein. In contrast, the gene faeD is strongly induced in the
      presence of ferulic acid, and FaeD is an extracellular protein secreted by the
      Out system, responsible for pectinase secretion. The product of the adjacent gene
      faeR is involved in the positive control of faeD in response to ferulic acid.
      Moreover, ferulic acid acts in synergy with polygalacturonate to induce pectate
      lyases, the main virulence determinant of soft rot disease. Feruloyl esterases
      dissociate internal cross-links in the polysaccharide network of the plant cell
      wall, suppress the polysaccharide esterifications, and liberate ferulic acid,
      which contributes to the induction of pectate lyases. Together, these effects of
      feruloyl esterases could facilitate soft rot disease caused by pectinolytic
      bacteria.

PMID- 21169495
TI  - Escherichia coli dihydropyrimidine dehydrogenase is a novel NAD-dependent
      heterotetramer essential for the production of 5,6-dihydrouracil.
AB  - The reductive pyrimidine catabolic pathway is absent in Escherichia coli.
      However, the bacterium contains an enzyme homologous to mammalian
      dihydropyrimidine dehydrogenase. Here, we show that E. coli dihydropyrimidine
      dehydrogenase is the first member of a novel NADH-dependent subclass of iron
      sulfur flavoenzymes catalyzing the conversion of uracil to 5,6-dihydrouracil in
      vivo.

PMID- 21169496
TI  - The putative hydrolase YycJ (WalJ) affects the coordination of cell division with
      DNA replication in Bacillus subtilis and may play a conserved role in cell wall
      metabolism.
AB  - Bacteria must accurately replicate and segregate their genetic information to
      ensure the production of viable daughter cells. The high fidelity of chromosome
      partitioning is achieved through mechanisms that coordinate cell division with
      DNA replication. We report that YycJ (WalJ), a predicted member of the metallo
      beta-lactamase superfamily found in most low-G+C Gram-positive bacteria,
      contributes to the fidelity of cell division in Bacillus subtilis. B. subtilis
      DeltawalJ (DeltawalJ(Bsu)) mutants divide over unsegregated chromosomes more
      frequently than wild-type cells, and this phenotype is exacerbated when DNA
      replication is inhibited. Two lines of evidence suggest that WalJ(Bsu) and its
      ortholog in the Gram-positive pathogen Streptococcus pneumoniae, WalJ(Spn)
      (VicX), play a role in cell wall metabolism: (i) strains of B. subtilis and S.
      pneumoniae lacking walJ exhibit increased sensitivity to a narrow spectrum of
      cephalosporin antibiotics, and (ii) reducing the expression of a two-component
      system that regulates genes involved in cell wall metabolism, WalRK (YycFG),
      renders walJ essential for growth in B. subtilis, as observed previously with S.
      pneumoniae. Together, these results suggest that the enzymatic activity of WalJ
      directly or indirectly affects cell wall metabolism and is required for accurate
      coordination of cell division with DNA replication.

PMID- 21169497
TI  - Pseudomonas aeruginosa enhances production of an antimicrobial in response to N
      acetylglucosamine and peptidoglycan.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen often associated with chronic
      lung infections in individuals with the genetic disease cystic fibrosis (CF).
      Previous work from our laboratory revealed that five genes predicted to be
      important for catabolism of N-acetylglucosamine (GlcNAc) are induced during in
      vitro growth in CF lung secretions (sputum). Here, we demonstrate that these
      genes comprise an operon (referred to as the nag operon) and that NagE, a
      putative component of the GlcNAc phosphotransferase system, is required for
      growth on and uptake of GlcNAc. Using primer extension analysis, the promoter of
      the nag operon was mapped and shown to be inducible by GlcNAc and regulated by
      the transcriptional regulator NagR. Transcriptome analysis revealed that in
      addition to induction of the nag operon, several P. aeruginosa genes encoding
      factors critical for extracellular antimicrobial production are also induced by
      GlcNAc. Finally, we show that the GlcNAc-containing polymer peptidoglycan induces
      production of the antimicrobial pyocyanin. Based on this data, we propose a model
      in which P. aeruginosa senses surrounding bacteria by monitoring exogenous
      peptidoglycan and responds to this cue through enhanced production of an
      antimicrobial.

PMID- 21169502
TI  - pH-sensitivity of the ribosomal peptidyl transfer reaction dependent on the
      identity of the A-site aminoacyl-tRNA.
AB  - We studied the pH-dependence of ribosome catalyzed peptidyl transfer from fMet
      tRNA(fMet) to the aa-tRNAs Phe-tRNA(Phe), Ala-tRNA(Ala), Gly-tRNA(Gly), Pro
      tRNA(Pro), Asn-tRNA(Asn), and Ile-tRNA(Ile), selected to cover a large range of
      intrinsic pK(a)-values for the alpha-amino group of their amino acids. The
      peptidyl transfer rates were different at pH 7.5 and displayed different pH
      dependence, quantified as the pH-value, pK(a)(obs), at which the rate was half
      maximal. The pK(a)(obs)-values were downshifted relative to the intrinsic pK(a)
      value of aa-tRNAs in bulk solution. Gly-tRNA(Gly) had the smallest downshift,
      while Ile-tRNA(Ile) and Ala-tRNA(Ala) had the largest downshifts. These
      downshifts correlate strongly with molecular dynamics (MD) estimates of the
      downshifts in pK(a)-values of these aa-tRNAs upon A-site binding. Our data show
      the chemistry of peptide bond formation to be rate limiting for peptidyl transfer
      at pH 7.5 in the Gly and Pro cases and indicate rate limiting chemistry for all
      six aa-tRNAs.

PMID- 21169503
TI  - Evolutionary twist on topoisomerases: conversion of gyrase to topoisomerase IV.

PMID- 21169504
TI  - Structural shifts of aldehyde dehydrogenase enzymes were instrumental for the
      early evolution of retinoid-dependent axial patterning in metazoans.
AB  - Aldehyde dehydrogenases (ALDHs) catabolize toxic aldehydes and process the
      vitamin A-derived retinaldehyde into retinoic acid (RA), a small diffusible
      molecule and a pivotal chordate morphogen. In this study, we combine
      phylogenetic, structural, genomic, and developmental gene expression analyses to
      examine the evolutionary origins of ALDH substrate preference. Structural
      modeling reveals that processing of small aldehydes, such as acetaldehyde, by
      ALDH2, versus large aldehydes, including retinaldehyde, by ALDH1A is associated
      with small versus large substrate entry channels (SECs), respectively. Moreover,
      we show that metazoan ALDH1s and ALDH2s are members of a single ALDH1/2 clade and
      that during evolution, eukaryote ALDH1/2s often switched between large and small
      SECs after gene duplication, transforming constricted channels into wide opened
      ones and vice versa. Ancestral sequence reconstructions suggest that during the
      evolutionary emergence of RA signaling, the ancestral, narrow-channeled metazoan
      ALDH1/2 gave rise to large ALDH1 channels capable of accommodating bulky
      aldehydes, such as retinaldehyde, supporting the view that retinoid-dependent
      signaling arose from ancestral cellular detoxification mechanisms. Our analyses
      also indicate that, on a more restricted evolutionary scale, ALDH1 duplicates
      from invertebrate chordates (amphioxus and ascidian tunicates) underwent switches
      to smaller and narrower SECs. When combined with alterations in gene expression,
      these switches led to neofunctionalization from ALDH1-like roles in embryonic
      patterning to systemic, ALDH2-like roles, suggesting functional shifts from
      signaling to detoxification.

PMID- 21169505
TI  - How to control the size and morphology of apatite nanocrystals in bone.

PMID- 21169507
TI  - It is not necessarily YY1--the frequently forgotten Yin-Yang-2 transcription
      factor.

PMID- 21169506
TI  - Testing the SNARE/SM protein model of membrane fusion.

PMID- 21169508
TI  - The Arabidopsis GTL1 transcription factor regulates water use efficiency and
      drought tolerance by modulating stomatal density via transrepression of SDD1.
AB  - A goal of modern agriculture is to improve plant drought tolerance and production
      per amount of water used, referred to as water use efficiency (WUE). Although
      stomatal density has been linked to WUE, the causal molecular mechanisms have yet
      to be determined. Arabidopsis thaliana GT-2 LIKE 1 (GTL1) loss-of-function
      mutations result in increased water deficit tolerance and higher integrated WUE
      by reducing daytime transpiration without a demonstrable reduction in biomass
      accumulation. gtl1 plants had higher instantaneous WUE that was attributable to
      ~25% lower transpiration and stomatal conductance but equivalent CO(2)
      assimilation. Lower transpiration was associated with higher STOMATAL DENSITY AND
      DISTRIBUTION1 (SDD1) expression and an ~25% reduction in abaxial stomatal
      density. GTL1 expression occurred in abaxial epidermal cells where the protein
      was localized to the nucleus, and its expression was downregulated by water
      stress. Chromatin immunoprecipitation analysis indicated that GTL1 interacts with
      a region of the SDD1 promoter that contains a GT3 box. An electrophoretic
      mobility shift assay was used to determine that the GT3 box is necessary for the
      interaction between GTL1 and the SDD1 promoter. These results establish that GTL1
      negatively regulates WUE by modulating stomatal density via transrepression of
      SDD1.

PMID- 21169510
TI  - Plasma vitamin K concentration in horses supplemented with several vitamin K
      homologs.
AB  - The effect of several vitamin K homologs on plasma vitamin K concentration was
      determined to assess their potential as a vitamin K supplement for adult horses.
      Sixteen Thoroughbred horses consisting of 8 mares and 8 geldings, aged 8.4 +/-
      3.6 yr and weighing 520.8 +/- 36.1 kg, were allocated to 4 groups (n = 4). Each
      group was given phylloquinone, menaquinone-4, or menadione at 58 umol/d, or no
      vitamin K supplement for 7 d. Plasma samples were collected before feeding, and
      2, 4, and 8 h after feeding on d 7, and plasma concentrations of phylloquinone
      and menaquinone-4 were determined. Plasma phylloquinone concentration was greater
      in the phylloquinone group than in the other groups (P < 0.001). The
      phylloquinone concentration quadratically increased (P < 0.001) after feeding in
      the phylloquinone group but no changes in the plasma phylloquinone concentration
      were observed after feeding in the other groups. Plasma menaquinone-4
      concentration was greater (P < 0.001) in the menadione group than the other
      groups, including the menaquinone-4 group. Menaquinone-4 concentration did not
      change (P = 0.192) after feeding in each group. Menaquinone-4 has been considered
      the most potent vitamin K homolog for bone metabolism; therefore, the present
      experiment indicates that menadione is a good source of vitamin K for bone health
      in horses because it is the only vitamin K homolog that increased the plasma
      concentrations of menaquinone-4.

PMID- 21169511
TI  - Triennial Growth Symposium: important roles for L-glutamine in swine nutrition
      and production.
AB  - L-Glutamine (Gln) has traditionally not been considered a nutrient needed in
      diets for livestock species or even mentioned in classic animal nutrition
      textbooks. This is due to previous technical difficulties in Gln analysis and the
      unsubstantiated assumption that animals can synthesize sufficient amounts of Gln
      to meet their needs. Consequently, the current (1998) version of NRC does not
      recommend dietary Gln requirements for swine. This lack of knowledge about Gln
      nutrition has contributed to suboptimal efficiency of global pig production.
      Because of recent advances in research, Gln is now known to be an abundant AA in
      physiological fluids and proteins and a key regulator of gene expression.
      Additionally, Gln can regulate cell signaling via the mammalian target of
      rapamycin pathway, adenosine monophosphate-activated protein kinase,
      extracellular signal-related kinase, Jun kinase, mitogen-activated protein
      kinase, and nitric oxide. The exquisite integration of Gln-dependent regulatory
      networks has profound effects on cell proliferation, differentiation, migration,
      metabolism, homeostasis, survival, and function. As a result of translating basic
      research into practice, dietary supplementation with 1% Gln maintains gut health
      and prevents intestinal dysfunction in low-birth-weight or early-weaned piglets
      while increasing their growth performance and survival. In addition,
      supplementing 1% Gln to a corn- and soybean-meal-based diet between d 90 and 114
      of gestation ameliorates fetal growth retardation in gilts and reduces preweaning
      mortality of piglets. Furthermore, dietary supplementation with 1% Gln enhances
      milk production by lactating sows. Thus, adequate amounts of dietary Gln, a major
      nutrient, are necessary to support the maximum growth, development, and
      production performance of swine.

PMID- 21169512
TI  - Relationship of ruminal temperature with parturition and estrus of beef cows.
AB  - Spring-calving Angus cows (n = 30) were used to evaluate changes in ruminal
      temperature (RuT) related to parturition and estrus. Cows were synchronized and
      artificially inseminated with semen from a single sire. Temperature boluses were
      placed in the rumen at 7.0 +/- 0.2 mo of gestation. Boluses were programmed to
      transmit RuT every 15 min. Cows (BW = 623 +/- 44 kg, BCS = 4.9 +/- 0.4) calved
      during 3 wk, and estrus was synchronized at 77 +/- 7 d after calving with
      PGF(2alpha). Cows were observed every 12 h to detect estrus. Daily average
      ambient temperatures ranged from 2 to 22  degrees C during parturition (February
      to March) and 17 to 25  degrees C during estrus (May to June). Ruminal
      temperature from 7 d before to 3 d after parturition and 2 d before to 2 d after
      visual detection of estrus was analyzed using the MIXED procedure. Ruminal
      temperatures <37.72  degrees C were attributed to water consumption and excluded
      from analyses. Day did not influence (P = 0.36) RuT from d -2 to -7 before
      parturition (38.94 +/- 0.05  degrees C). Ruminal temperature decreased (P <
      0.001) from d -2 to d -1 before parturition (38.88 +/- 0.05 to 38.55 +/- 0.05 
      degrees C, respectively). Ruminal temperature was not influenced (P = 0.23) by
      day from 1 d before to 3 d after parturition (38.49 +/- 0.05  degrees C). Ruminal
      temperature at 0 to 8 h after detection of estrus (38.98 +/- 0.09  degrees C) was
      greater (P < 0.001) compared with RuT at the same daily hour of the day before
      (38.37 +/- 0.11  degrees C) or the day after estrus (38.30 +/- 0.09  degrees C).
      Ambient temperature did not influence (P > 0.30) RuT at parturition or estrus.
      Ruminal temperature decreased the day before parturition and increased at estrus
      in spring-calving beef cows and has potential use as a predictor of parturition
      and estrus.

PMID- 21169509
TI  - RanGAP2 mediates nucleocytoplasmic partitioning of the NB-LRR immune receptor Rx
      in the Solanaceae, thereby dictating Rx function.
AB  - The potato (Solanum tuberosum) nucleotide binding-leucine-rich repeat immune
      receptor Rx confers resistance to Potato virus X (PVX) and requires Ran GTPase
      activating protein 2 (RanGAP2) for effective immune signaling. Although Rx does
      not contain a discernible nuclear localization signal, the protein localizes to
      both the cytoplasm and nucleus in Nicotiana benthamiana. Transient coexpression
      of Rx and cytoplasmically localized RanGAP2 sequesters Rx in the cytoplasm. This
      relocation of the immune receptor appeared to be mediated by the physical
      interaction between Rx and RanGAP2 and was independent of the concomitant
      increased GAP activity. Coexpression with RanGAP2 also potentiates Rx-mediated
      immune signaling, leading to a hypersensitive response (HR) and enhanced
      resistance to PVX. Besides sequestration, RanGAP2 also stabilizes Rx, a process
      that likely contributes to enhanced defense signaling. Strikingly, coexpression
      of Rx with the Rx-interacting WPP domain of RanGAP2 fused to a nuclear
      localization signal leads to hyperaccumulation of both the WPP domain and Rx in
      the nucleus. As a consequence, both Rx-mediated resistance to PVX and the HR
      induced by auto-active Rx mutants are significantly suppressed. These data show
      that a balanced nucleocytoplasmic partitioning of Rx is required for proper
      regulation of defense signaling. Furthermore, our data indicate that RanGAP2
      regulates this partitioning by serving as a cytoplasmic retention factor for Rx.

PMID- 21169513
TI  - Physiology and endocrinology symposium: role of the oviduct in maintaining
      sustained fertility in hens.
AB  - In poultry, sperm transferred by natural mating or AI into the distal end of the
      vagina immediately begin their ascent to the uterovaginal junction (UVJ) at the
      anterior end of the vagina. However, due to an intense selection process in the
      vagina, less than 1% of the sperm transferred actually reach the UVJ. Those sperm
      that do reach the UVJ enter numerous tubular invaginations of the surface
      epithelium of the vagina located in the UVJ mucosa, collectively referred to as
      the sperm-storage tubules (SST). Sperm residing in the SST lumen are capable of
      surviving up to several weeks while retaining their fertilizing capacity.
      Resident sperm are released gradually from the SST while the hen is in egg
      production, ascend to the site of fertilization, and interact with the next
      ovulated ovum. In this manner, given the absence of an estrus to synchronize
      ovulation with copulation, poultry are ensured a population of sperm at the site
      of fertilization around ovulation. Over the past decade, several new and diverse
      observations have been published addressing the microanatomy of the UVJ and SST,
      and the cellular and molecular mechanisms orchestrating oviductal sperm selection
      and storage. These include the role of sperm mobility in selection and transport,
      SST numbers in different poultry species and lines of high and low fertility,
      roles of the immune system and possibly neuroendocrine-like cells in the vagina
      in sperm selection and storage, and the roles of aquaporins and a fluid exchange
      mechanisms contributing to sperm release from the SST. The objective of this
      paper is to review and integrate these observations into a comprehensive
      understanding of the cellular and molecular events influencing the fate of sperm
      in the oviduct of the hen, particularly with regard to oviductal sperm selection
      and storage.

PMID- 21169514
TI  - Rumen temperature change monitored with remote rumen temperature boluses after
      challenges with bovine viral diarrhea virus and Mannheimia haemolytica.
AB  - Remote rumen temperature monitoring is a potential method for early disease
      detection in beef cattle. This experiment was conducted to determine if remotely
      monitored rumen temperature boluses could detect a temperature change in steers
      exposed to bovine viral diarrhea virus (BVDV) and challenged with a common bovine
      respiratory disease pathogen, Mannheimia haemolytica (MH). Twenty-four Angus
      crossbred steers (BW = 313 +/- 31 kg) were allotted to 1 of 4 treatments: 1) no
      challenge (control); 2) challenge by a 72-h exposure to 2 steers persistently
      infected with BVDV; 3) bacterial challenge with MH; and 4) viral challenge by a
      72-h exposure to 2 steers persistently infected with BVDV followed by bacterial
      challenge with MH (BVDV + MH). Remotely monitored rumen temperature boluses
      programmed to transmit temperature every minute were placed in the rumen before
      the time of exposure to steers persistently infected with BVDV. Rectal
      temperatures were taken before MH challenge (0) and at 2, 4, 6, 12, 18, 24, 36,
      48, 72, and 96 h after MH challenge. Rumen temperatures were recorded 3 d before
      (-72 h; period of BVDV exposure) through 14 d after (336 h) MH challenge. Rumen
      temperatures were analyzed as a randomized complete block design with a 2 * 2
      factorial arrangement of treatments and a first-order autoregressive covariance
      structure for repeated measures. A treatment * day interaction was observed for
      average daily rumen temperature (P < 0.01). A treatment difference (P < 0.01) was
      observed on d 0, when MH-challenged steers had greater rumen temperatures than
      steers not challenged with MH. There was no BVDV * day interaction (P > 0.01).
      Rumen temperatures averaged every 2 h resulted in a BVDV * hour interaction (P <
      0.01) and an MH * hour interaction (P < 0.01). The BVDV * hour differences
      occurred at h -18 to -14, 40 to 46, 110, 122, and 144 to 146 (P < 0.01). The MH *
      hour difference occurred at h 4 to 24 (P < 0.01). Maximum rumen temperature was
      increased (P < 0.01) for BVDV (0.8  degrees C), MH (1.2  degrees C), and BVDV +
      MH (1.3  degrees C) compared with the control. On average, rumen temperatures
      measured by the boluses at the same time points as the rectal temperatures were
      0.13  degrees C less than rectal temperatures, and the 2 body temperatures were
      highly correlated (r = 0.89). Rumen temperature boluses appear to have potential
      as a tool for detecting temperature changes associated with adverse health events
      such as exposure to bovine respiratory disease and BVDV.

PMID- 21169515
TI  - Effect of vaccination of boars against porcine circovirus type 2 on ejaculate
      characteristics, serum antibody titers, viremia, and semen virus shedding.
AB  - The objective of this research was to determine the effect of vaccination against
      porcine circovirus type 2 (PCV2) on ejaculate characteristics, PCV2-specific
      antibody titers in serum, viremia, and viral shedding in the semen of PCV2
      positive boars. Before vaccination, all boars were confirmed by PCR to be
      naturally infected with PCV2. The boars were vaccinated with a commercial killed
      vaccine against PCV2 (n = 5) or served as controls and received 2 mL of 0.9%
      saline (n = 5). Semen and blood samples were collected before vaccination at wk 0
      and at 7-d intervals thereafter until wk 8. Sperm concentration and
      characteristics of sperm motility were assessed using a computer-assisted sperm
      analysis system, and sperm morphology was evaluated using light microscopy after
      staining. The PCV2 antibody titers were determined in serum using an ELISA, and
      the genomic copy numbers of PCV2 DNA in serum and semen were determined by real
      time PCR. In general, there were no effects of treatment or treatment * week on
      semen or sperm characteristics (P > 0.10). An effect of treatment * week was
      detected for serum antibody titers (P < 0.01). Compared with controls, PCV2
      antibody titers in vaccinated boars were less (P < 0.01) at wk 7 (1.01 +/- 0.05
      titer/mL vs. 1.23 +/- 0.05 titer/mL) and tended (P = 0.07) to be less at wk 8
      (1.05 +/- 0.05 titer/mL vs. 1.17 +/- 0.05 titer/mL). There were no effects of
      treatment or treatment * week for serum and semen genomic copy numbers of PCV2
      DNA (P > 0.10). There was a tendency (P = 0.09) for an effect of week on serum
      viral load. It was evident that during this experiment, boars experienced
      reoccurring PCV2 infection, and the detection of an increased PCV2 DNA load in
      serum preceded that in semen; the duration of reoccurring infection appeared to
      be less in vaccinated boars compared with controls. In summary, vaccination
      against PCV2 can reduce antibody titers when given postinfection and has no
      dramatic effect on indicators of semen quality. Vaccination against PCV2 in
      naturally infected boars can also decrease the length of reoccurring infection
      and decrease the duration of viral shedding in semen.

PMID- 21169516
TI  - Cattle temperament: persistence of assessments and associations with
      productivity, efficiency, carcass and meat quality traits.
AB  - Relationships between temperament and a range of performance, carcass, and meat
      quality traits in young cattle were studied in 2 experiments conducted in New
      South Wales (NSW) and Western Australia (WA), Australia. In both experiments,
      growth rates of cattle were assessed during backgrounding on pasture and grain
      finishing in a feedlot. Carcass and objective meat quality characteristics were
      measured after slaughter. Feed intake and efficiency during grain finishing were
      also determined in NSW. Brahman (n = 82 steers and 82 heifers) and Angus (n = 25
      steers and 24 heifers) cattle were used in the NSW experiment. In NSW,
      temperament was assessed by measuring flight speed [FS, m/s on exit from the
      chute (crush)] on 14 occasions, and by assessing agitation score during
      confinement in the crush (CS; 1 = calm to 5 = highly agitated) on 17 occasions
      over the course of the experiment. Brahman (n = 173) and Angus (n = 20) steers
      were used in the WA experiment. In WA, temperament was assessed by measuring FS
      on 2 occasions during backgrounding and on 2 occasions during grain feeding. At
      both sites, a hormonal growth promotant (Revalor-H, Virbac, Milperra, New South
      Wales, Australia) was applied to one-half of the cattle at feedlot entry, and the
      Brahman cattle were polymorphic for 2 calpain-system markers for beef tenderness.
      Temperament was not related (most P > 0.05) to tenderness gene marker status in
      Brahman cattle and was not (all P > 0.26) modified by the growth promotant
      treatment in either breed. The Brahman cattle had greater individual variation
      in, and greater correlations within and between, repeated assessments of FS and
      CS than did the Angus cattle. Correlations for repeated measures of FS were
      greater than for repeated assessments of CS, and the strength of correlations for
      both declined over time. Average FS or CS for each experiment and location (NSW
      or WA * backgrounding or finishing) were more highly correlated than individual
      measurements, indicating that the average values were a more reliable assessment
      of cattle temperament than any single measure. In Brahman cattle, increased
      average FS and CS were associated with significant (P < 0.05) reductions in
      backgrounding and feedlot growth rates, feed intake and time spent eating,
      carcass weight, and objective measures of meat quality. In Angus cattle, the
      associations between temperament and growth rates, feed intake, and carcass
      traits were weaker than in Brahmans, although the strength of relationships with
      meat quality were similar.

PMID- 21169517
TI  - CD97 antibody depletes granulocytes in mice under conditions of acute
      inflammation via a Fc receptor-dependent mechanism.
AB  - Antibodies to the pan-leukocyte adhesion-GPCR CD97 efficiently block neutrophil
      recruitment in mice, thereby reducing antibacterial host defense, inflammatory
      disease, and hematopoietic stem cell mobilization. Here, we investigated the
      working mechanism of the CD97 antibody 1B2. Applying sterile models of
      inflammation, intravital microscopy, and mice deficient for the CD97L CD55, the
      complement component C3, or the FcR common gamma-chain, we show that 1B2 acts in
      vivo independent of ligand-binding interference by depleting PMN granulocytes in
      bone marrow and blood. Granulocyte depletion with 1B2 involved FcR but not
      complement activation and was associated with increased serum levels of TNF and
      other proinflammatory cytokines. Notably, depletion of granulocytes by CD97
      antibody required acute inflammation, suggesting a mechanism of conditional,
      antibody-mediated granulocytopenia.

PMID- 21169518
TI  - Macrophage phagocytosis of neutrophils at inflammatory/infectious foci: a
      cooperative mechanism in the control of infection and infectious inflammation.
AB  - Macrophages and neutrophils possess overlapping and complementary features
      associated to their common origin and subsequent specialization during
      myelopoiesis. That specialization results in macrophage lineage being limited in
      antimicrobial capacity and cytotoxicity comparatively with the neutrophil
      lineage. These and other features of mature macrophages and neutrophils, like
      different lifespan and tissue localization, promote their particular lifestyles
      and prompt a functional partnership for cooperation in the protective
      antimicrobial host defense. This partnership includes reciprocal recruitment to
      infected sites, cooperative effector antimicrobial activities, and pro-resolving
      anti-inflammatory effects. One modality of the cooperative effector antimicrobial
      activities involves the phagocytosis by the macrophage of apoptosing neutrophils
      and of nonapoptosing neutrophils expressing "eat-me" signals. This cooperative
      interaction results in the enhancement of the comparatively limited macrophage
      antimicrobial capacity by the acquisition and use of potent neutrophil
      microbicidal molecules. Here, data are reviewed that suggest that this is a
      process actively engaging the two professional phagocytes. Phagocytosis of
      neutrophils by macrophages at inflammatory/infectious foci accumulates two
      effects beneficial to the protective host immune response: help in the control of
      the infection and prevention of neutrophil autolysis, effects that converge to
      accelerate the resolution of the infection-associated inflammation.

PMID- 21169519
TI  - Applications of myeloid-specific promoters in transgenic mice support in vivo
      imaging and functional genomics but do not support the concept of distinct
      macrophage and dendritic cell lineages or roles in immunity.
AB  - Myeloid lineage cells contribute to innate and acquired immunity, homeostasis,
      wound repair, and inflammation. There is considerable interest in manipulation of
      their function in transgenic mice using myeloid-specific promoters. This review
      considers the applications and specificity of some of the most widely studied
      transgenes, driven by promoter elements of the lysM, csf1r, CD11c, CD68,
      macrophage SRA, and CD11b genes, as well as several others. Transgenes have been
      used in mice to generate myeloid lineage-specific cell ablation, expression of
      genes of interest, including fluorescent reporters, or deletion via
      recombination. In general, the specificity of such transgenes has been
      overinterpreted, and none of them provide well-documented, reliable, differential
      expression in any specific myeloid cell subset, macrophages, granulocytes, or
      myeloid DCs. Nevertheless, they have proved valuable in cell isolation,
      functional genomics, and live imaging of myeloid cell behavior in many different
      pathologies.

PMID- 21169520
TI  - Vascular inflammation in central nervous system diseases: adhesion receptors
      controlling leukocyte-endothelial interactions.
AB  - Leukocyte trafficking from the blood into the tissues represents a key process
      during inflammation and requires multiple steps mediated by adhesion molecules
      and chemoattractants. Inflammation has a detrimental role in several diseases,
      and in such cases, the molecular mechanisms controlling leukocyte migration are
      potential therapeutic targets. Over the past 20 years, leukocyte migration in the
      CNS has been investigated almost exclusively in the context of stroke and MS.
      Experimental models of ischemic stroke have led to the characterization of
      adhesion molecules controlling leukocyte migration during acute inflammation,
      whereas EAE, the animal model of MS, has provided similar data for chronic
      inflammation. Such experiments have led to clinical trials of antileukocyte
      adhesion therapy, with consistently positive outcomes in human subjects with MS,
      showing that interference with leukocyte adhesion can ameliorate chronic
      inflammatory CNS diseases. This review summarizes our current understanding of
      the roles of adhesion molecules controlling leukocyte-endothelial interactions in
      stroke and MS, focusing on recently discovered, novel migration mechanisms. We
      also discuss the growing evidence suggesting a role for vascular inflammation and
      leukocyte trafficking in neurodegenerative diseases such as AD. Moreover, we
      highlight recent findings suggesting a role for leukocyte-endothelial
      interactions in the pathogenesis of seizures and epilepsy, thus linking
      endothelial activation and leukocyte trafficking to neuronal electrical
      hyperactivity. These emerging roles for leukocytes and leukocyte adhesion
      mechanisms in CNS diseases provide insight into the mechanisms of brain damage
      and may contribute to the development of novel therapeutic strategies.

PMID- 21169521
TI  - Macrophage-derived BAFF induces AID expression through the p38MAPK/CREB and
      JNK/AP-1 pathways.
AB  - BAFF is expressed primarily by macrophages and DCs. BAFF stimulates the
      differentiation and survival of B cells and induces Ig production. We have
      demonstrated previously that murine macrophages treated with TGF-beta1 or IFN
      gamma express membrane-bound and soluble forms of BAFF. The ability of these two
      forms of BAFF to induce expression of AID, which plays a critical role in Ig CSR
      in B cells, was investigated. Both forms of BAFF, derived from macrophages
      activated by IFN-gamma or TGF-beta1, can increase AID expression. Subsequent
      analysis of BAFF signaling suggested that BAFF induces AID through BCMA, a BAFF
      receptor, and p38MAPK and CREB act as intermediates in AID expression. In
      addition, JNK and AP-1 have similar activities. Our findings suggest that
      macrophage-derived BAFF stimulates B cells to express AID through BCMA and at
      least two different pathways, including the p38MAPK/CREB and the JNK/AP-1
      pathways.

PMID- 21169522
TI  - "He loves me, he loves me not . . . ": uncertainty can increase romantic
      attraction.
AB  - This research qualifies a social psychological truism: that people like others
      who like them (the reciprocity principle). College women viewed the Facebook
      profiles of four male students who had previously seen their profiles. They were
      told that the men (a) liked them a lot, (b) liked them only an average amount, or
      (c) liked them either a lot or an average amount (uncertain condition).
      Comparison of the first two conditions yielded results consistent with the
      reciprocity principle. Participants were more attracted to men who liked them a
      lot than to men who liked them an average amount. Results for the uncertain
      condition, however, were consistent with research on the pleasures of
      uncertainty. Participants in the uncertain condition were most attracted to the
      men-even more attracted than were participants who were told that the men liked
      them a lot. Uncertain participants reported thinking about the men the most, and
      this increased their attraction toward the men.

PMID- 21169523
TI  - Escalating slant: increasing physiological potential does not reduce slant
      overestimates.

PMID- 21169524
TI  - Emergence of a Gene x socioeconomic status interaction on infant mental ability
      between 10 months and 2 years.
AB  - Recent research in behavioral genetics has found evidence for a Gene *
      Environment interaction on cognitive ability: Individual differences in cognitive
      ability among children raised in socioeconomically advantaged homes are primarily
      due to genes, whereas environmental factors are more influential for children
      from disadvantaged homes. We investigated the developmental origins of this
      interaction in a sample of 750 pairs of twins measured on the Bayley Short Form
      test of infant mental ability, once at age 10 months and again at age 2 years. A
      Gene * Environment interaction was evident on the longitudinal change in mental
      ability over the study period. At age 10 months, genes accounted for negligible
      variation in mental ability across all levels of socioeconomic status (SES).
      However, genetic influences emerged over the course of development, with larger
      genetic influences emerging for infants raised in higher-SES homes. At age 2
      years, genes accounted for nearly 50% of the variation in mental ability of
      children raised in high-SES homes, but genes continued to account for negligible
      variation in mental ability of children raised in low-SES homes.

PMID- 21169525
TI  - TGF-beta induces sustained upregulation of SNAI1 and SNAI2 through Smad and non
      Smad pathways in a human corneal epithelial cell line.
AB  - PURPOSE: The aim of this study was to investigate the expression changes of
      epithelial mesenchymal transition (EMT)-related molecules induced by TGF-beta
      signaling in a human corneal epithelial cell line (HCECs). METHODS: The cellular
      response to TGF-beta was evaluated by immunoblotting, quantitative real-time RT
      PCR, and immunofluorescence microscopy in HCECs. RESULTS: TGF-beta significantly
      increased mRNA expression of SNAI1, SNAI2, VIM, and FN1, but not TWIST1 through
      Smad and non-Smad pathways in HCECs. Protein expression of a mesenchymal marker N
      cadherin was dose-dependently increased and that of an epithelial marker of E
      cadherin was decreased by TGF-beta. TGF-beta, but not EGF, mediated the EMT-like
      morphologic changes. Both TGF-beta and EGF were capable of upregulating SNAI1 and
      SNAI2 by about two-fold within a short response time. However, a detailed time
      course analysis revealed drastically different expression patterns, with TGF-beta
      mediating a sustained upregulation of SNAI1 and SNAI2 for at least for 6 days and
      EGF allowing a return to the baseline expression values after 8 ~ 12 h. These
      data indicate that TGF-beta, but not EGF, induces sustained upregulation of SNAI1
      and SNAI2 in HCECs. CONCLUSIONS: TGF-beta induces sustained upregulation of SNAI1
      and SNAI2 through Smad and non-Smad pathways, EMT-like morphologic changes,
      downregulation of E-cadherin, and upregulation of N-cadherin in HCECs. The
      authors' findings provide insight into the TGF-beta signaling and the temporal
      expression patterns of EMT-inducible transcription factors in HCECs.

PMID- 21169526
TI  - Role of CD44+ stem cells in mural cell formation in the human choroid: evidence
      of vascular instability due to limited pericyte ensheathment.
AB  - PURPOSE: To examine mural cell differentiation and pericyte ensheathment during
      human choroidal vascular formation and into adulthood. METHODS: Triple- and
      double-labeled immunohistochemistry (alpha-smooth muscle actin [alphaSMA],
      desmin, NG2, calponin, caldesmon, CD44, CD34, and CD39) were applied to human
      fetal (8-32 weeks' gestation) and adult choroidal and retinal wholemounts and
      histologic cross-sections. Transmission electron microscopy (TEM) was also
      undertaken. RESULTS: Early in development CD44+ stem cells also stained with
      alphaSMA and CD39, suggesting a common precursor. At 12 weeks' gestation,
      alphaSMA+ mural precursor cells, confirmed by TEM, were found scattered and
      isolated over the primordial vascular tree. During development, alphaSMA+ cells
      formed a continuous sheath around large arterioles; in veins there were gaps in
      alphaSMA expression. The choriocapillaris had an extensive vascular bed but
      limited coverage by alphaSMA+ and NG2+ mural cells. Calponin was expressed only
      on large vessels, and no caldesmon was detected. Pericyte ensheathment of adult
      capillaries was 11% for choroid versus 94% for retina. Remarkably, choroidal
      pericytes had no visible intermediate filaments (IFs) on TEM, though IFs were
      present in retinal pericytes. Neither retinal nor choroidal pericytes stained
      with desmin. CONCLUSIONS: CD44+ stem cells are involved in the formation of mural
      cells in the human choroidal vasculature. A marked reduction in pericyte
      ensheathment of human choroidal vessels suggests a permanently open "plasticity
      window" and a predisposition to vascular instability and poor autoregulatory
      ability.

PMID- 21169528
TI  - Pax6 regulates proliferation and apoptosis of human retinoblastoma cells.
AB  - PURPOSE: To assess whether the Pax6 gene is involved in the development of
      retinoblastoma. METHODS: Three human retinoblastoma cell cultures were
      transfected with human Pax6 specific double-stranded, small interfering siRNA
      molecules RH-1 and RH-2. In addition, untreated control groups and negative
      control groups (CT groups) transfected with siRNA without homology to the human
      genome were formed for all three cell culture lines. RESULTS: After Pax6 gene was
      silenced by siRNA, the percentage of tumor cell survival decreased significantly
      (P < 0.05). Correspondingly, the percentage of apoptotic cells to total cells was
      significantly (P < 0.05) higher in the three retinoblastoma cell lines
      transfected with siRNA than in the CT control groups and the untreated control
      groups. In a parallel manner, the cell cycle was significantly (P < 0.01) altered
      in the transfected study groups, with reduced percentages of retinoblastoma cells
      in the S-phase. The cell-cycle-associated protein P21 was upregulated, and the
      protein P27 was slightly upregulated in the transfected retinoblastoma cell
      lines, in comparison to the control groups. CONCLUSIONS: Silencing the Pax6 gene
      with short interfering RNA resulted in an inhibited growth and an increased
      apoptosis of cultured human retinoblastoma cells. It was paralleled by
      upregulation of the P21 and P27 proteins.

PMID- 21169527
TI  - Gene therapy rescues cone structure and function in the 3-month-old rd12 mouse: a
      model for midcourse RPE65 leber congenital amaurosis.
AB  - PURPOSE: RPE65 function is necessary in the retinal pigment epithelium (RPE) to
      generate chromophore for all opsins. Its absence results in vision loss and rapid
      cone degeneration. Recent Leber congenital amaurosis type 2 (LCA with RPE65
      mutations) phase I clinical trials demonstrated restoration of vision on RPE65
      gene transfer into RPE cells overlying cones. In the rd12 mouse, a naturally
      occurring model of RPE65-LCA early cone degeneration was observed; however, some
      peripheral M-cones remained. A prior study showed that AAV-mediated RPE65
      expression can prevent early cone degeneration. The present study was conducted
      to test whether the remaining cones in older rd12 mice can be rescued. METHODS:
      Subretinal treatment with the scAAV5-smCBA-hRPE65 vector was initiated at
      postnatal day (P)14 and P90. After 2 months, electroretinograms were recorded,
      and cone morphology was analyzed by using cone-specific peanut agglutinin and
      cone opsin-specific antibodies. RESULTS: Cone degeneration started centrally and
      spread ventrally, with cells losing cone-opsin staining before that for the PNA
      lectin-positive cone sheath. Gene therapy starting at P14 resulted in almost wild
      type M- and S-cone function and morphology. Delaying gene-replacement rescued the
      remaining M-cones, and most important, more M-cone opsin-positive cells were
      identified than were present at the onset of gene therapy, suggesting that opsin
      expression could be reinitiated in cells with cone sheaths. CONCLUSIONS: The
      results support and extend those of the previous study that gene therapy can stop
      early cone degeneration, and, more important, they provide proof that delayed
      treatment can restore the function and morphology of the remaining cones. These
      results have important implications for the ongoing LCA2 clinical trials.

PMID- 21169529
TI  - 3-D characterization of the corneal shape in Fuchs dystrophy and pseudophakic
      keratopathy.
AB  - PURPOSE: To characterize the 3-D corneal shape deformation incurred by Fuchs
      corneal dystrophy and pseudophakic bullous keratopathy by using the integrated
      analysis of Orbscan (Bausch & Lomb Surgical, Rochester, NY) topographic maps of
      affected and normal corneas. METHODS: One hundred thirty-seven patients with
      Fuchs dystrophy or pseudophakic keratopathy were divided into three groups
      according to the severity of the disease: mild (central corneal thickness [CCT],
      500-710 MUm; n = 46); moderate (710-775 MUm; n = 45), and severe (775-1100 MUm; n
      = 46). A control group included 411 normal subjects matched for age and
      refractive spherical equivalent (three control subjects for each subject with
      Fuchs or pseudophakic keratopathy). The four groups were compared by using 3-D
      corneal shape atlases illustrating mean anterior elevation, posterior elevation,
      and pachymetry. RESULTS: Whereas the atlases showed little anterior surface
      deformation, the posterior surface presented a significant central bulging toward
      the anterior chamber. The thinnest point was displaced away from the center,
      toward the superior nasal midperiphery. The corneal periphery remained relatively
      unaffected by the disease, except in the final stage. CONCLUSIONS: 3-D atlases
      provided detailed new information on the 3-D corneal shape deformation incurred
      by Fuchs corneal dystrophy throughout disease progression.

PMID- 21169530
TI  - Prophylactic effect of intravenous moxifloxacin in a rabbit model of
      Staphylococcus epidermidis endophthalmitis.
AB  - PURPOSE: To compare the prophylactic effects of intravenous moxifloxacin and
      vancomycin for Staphylococcus epidermidis endophthalmitis in a rabbit model.
      METHODS: Albino rabbits (n = 60) were divided into three groups. Intravenous
      moxifloxacin was injected into 20 animals (group 1), and intravenous vancomycin
      was injected into 20 animals (group 2). In group 3, 20 animals received 0.9%
      normal saline. After these prophylactic intravenous injections, the right eyes of
      the 60 rabbits were injected intravitreally with 10(5) colony-forming units of S.
      epidermidis. Intravenous antibiotic injection was repeated on days 1, 2, and 3
      after infection. Clinical features were evaluated on days 1, 3, 5, and 7 after
      infection, and 10 eyes per group were then enucleated for histopathologic
      examination. Vitreous aspirates were obtained for bacterial culture on days 1, 3,
      5, and 7 after infection from the other 10 eyes per group. RESULTS: The
      moxifloxacin group showed significant clinical effects at days 1, 3, 5, and 7 (P
      = 0.019, < 0.001, < 0.001, and < 0.001, respectively); bacteriologic results at
      days 1, 3, 5, and 7 (P = 0.001, 0.002, 0.01, and 0.002, respectively); and
      histopathologic results, with less severe inflammation and relatively well
      preserved retinal architecture. However, no difference was detected between the
      vancomycin group and control group in any aspect examined. CONCLUSIONS:
      Intravenously administered moxifloxacin showed a significant prophylactic effect
      against S. epidermidis endophthalmitis. Thus, intravenous moxifloxacin may be a
      useful prophylactic medication against postoperative endophthalmitis.

PMID- 21169531
TI  - Dissection of chromosome 16p12 linkage peak suggests a possible role for CACNG3
      variants in age-related macular degeneration susceptibility.
AB  - PURPOSE: Age-related macular degeneration (AMD) is a complex disorder of the
      retina, characterized by drusen, geographic atrophy, and choroidal
      neovascularization. Cigarette smoking and the genetic variants CFH Y402H, ARMS2
      A69S, CFB R32Q, and C3 R102G have been strongly and consistently associated with
      AMD. Multiple linkage studies have found evidence suggestive of another AMD locus
      on chromosome 16p12 but the gene responsible has yet to be identified. METHODS:
      In the initial phase of the study, single-nucleotide polymorphisms (SNPs) across
      chromosome 16 were examined for linkage and/or association in 575 Caucasian
      individuals from 148 multiplex and 77 singleton families. Additional variants
      were tested in an independent dataset of unrelated cases and controls. According
      to these results, in combination with gene expression data and biological
      knowledge, five genes were selected for further study: CACNG3, HS3ST4, IL4R,
      Q7Z6F8, and ITGAM. RESULTS: After genotyping additional tagging SNPs across each
      gene, the strongest evidence for linkage and association was found within CACNG3
      (rs757200 nonparametric LOD* = 3.3, APL (association in the presence of linkage)
      P = 0.06, and rs2238498 MQLS (modified quasi-likelihood score) P = 0.006 in the
      families; rs2283550 P = 1.3 * 10(-6), and rs4787924 P = 0.002 in the case-control
      dataset). After adjusting for known AMD risk factors, rs2283550 remained strongly
      associated (P = 2.4 * 10(-4)). Furthermore, the association signal at rs4787924
      was replicated in an independent dataset (P = 0.035) and in a joint analysis of
      all the data (P = 0.001). CONCLUSIONS: These results suggest that CACNG3 is the
      best candidate for an AMD risk gene within the 16p12 linkage peak. More studies
      are needed to confirm this association and clarify the role of the gene in AMD
      pathogenesis.

PMID- 21169532
TI  - The effect of graded cyclic stretching on extracellular matrix-related gene
      expression profiles in cultured primary human lamina cribrosa cells.
AB  - PURPOSE: Cyclic stretching of the glial fibrillary acidic protein (GFAP)-negative
      lamina cribrosa (LC) cell in vitro is associated with transcriptomic changes in
      genes involved in extracellular matrix (ECM) dynamics in vivo, thereby
      implicating this cell type in the pathophysiologic changes of the optic nerve
      head (ONH) in glaucoma. The purpose of the study was to determine whether
      exposure to different grades of mechanical stretch progressively alters the
      expression of ECM genes in cultured LC cells. METHODS: Primary cultures of human
      LC cells from three separate donors were maintained in static culture or exposed
      to low-level strain (3% +/- 0.5% elongation, 1 Hz) for 24 hours. A baseline
      comparison of the expression of 62 genes involved in ECM dynamics was performed
      with low-density gene arrays (LDAs). The 3% protocol was used in a 24-hour period
      of baseline dynamic low-level stretch, and gene expression was compared with that
      occurring in a further 24-hour exposure to a 12.5% or a 20% stretch. Gene
      expression levels were determined by qRT-PCR. RESULTS: LC cells displayed a
      nonlinear, transcriptional response to the mechanical stretch. Ten ECM-related
      and growth factor genes were altered by 3% strain versus static culture (nine
      downregulated and one upregulated). Increasing strain from 3% to 20% resulted in
      a significant increase in expression of 15 ECM-elated genes. Only one gene
      (epidermal growth factor) was increased between the 3% and 12.5% strains.
      CONCLUSIONS: Low-level, pulsatile, cyclic strain resets a lower baseline
      expression of several glaucoma-associated ECM genes. The LC ECM gene response
      occurs above a fourfold increase in baseline strain (12.5% strain) in vitro. The
      study supports the use of a nonstatic baseline when studying the effect of
      stretch (or strain) on the activation of ONH-derived, ECM-producing cells.

PMID- 21169533
TI  - Outflow physiology of the mouse eye: pressure dependence and washout.
AB  - PURPOSE: Mice are commonly used in glaucoma research, but relatively little is
      known about aqueous outflow dynamics in the species. To facilitate future use of
      the mouse as a model of aqueous humor outflow, several fundamental physiological
      parameters were measured in the mouse eye. METHODS: Eyes from adult mice of
      either sex (C57BL/6 background) were enucleated, cannulated with a 33-gauge
      needle, and perfused at constant pressure while inflow was continuously measured.
      RESULTS: At 8 mm Hg, total outflow facility (C(total)) was 0.022 +/- 0.005
      MUL/min/mm Hg (all values mean +/- SD; n = 21). The flow-pressure relationship
      was linear up to 35 mm Hg. The conventional outflow facility (C(conv)) was 0.0066
      +/- 0.0009 MUL/min/mm Hg, and the unconventional outflow (F(u)) was 0.114 +/-
      0.019 MUL/min, both measured at room temperature. At 8 mm Hg, 66% of the outflow
      was via the unconventional pathway. In a more than 2-hour-long perfusion at 8 mm
      Hg, the rate of facility change was 2.4% +/- 5.4% (n = 11) of starting facility
      per hour. The ocular compliance (0.086 +/- 0.017 MUL/mm Hg; n = 5) was comparable
      to the compliance of the perfusion system (0.100 +/- 0.004 MUL/mm Hg).
      CONCLUSIONS: Mouse eyes are similar to human eyes, in that they have no
      detectable washout rate and a linear pressure-flow relationship over a broad
      range of intraocular pressures. Because of the absence of washout and the
      apparent presence of a true Schlemm's canal, the mouse is a useful model for
      studying the physiology of the inner wall of Schlemm's canal and the conventional
      outflow tissues.

PMID- 21169534
TI  - In vivo confocal microscopy of meibomian glands in Sjogren's syndrome.
AB  - PURPOSE: To evaluate morphologic changes in meibomian glands (MGs) and the status
      of periglandular inflammation in patients with primary and secondary Sjogren's
      Syndrome (SS) using in vivo confocal laser microscopy (LSCM). METHODS: Twenty
      patients with primary SS (SSI), 25 with secondary SS (SSII), 20 with MG
      dysfunction (MGD), and 25 age- and gender-matched control subjects were enrolled
      consecutively. Each participant completed an Ocular Surface Disease Index
      questionnaire and underwent a full eye examination, including tear film break-up
      time (BUT), fluorescein and lissamine green staining, Schirmer test, and an LSCM
      examination of the MGs, the last to determine acinar unit density and diameter,
      glandular orifice diameters, meibum secretion reflectivity, inhomogeneous
      appearance of glandular interstice, and acinar wall. RESULTS: All parameters
      indicated statistically significant differences among groups (P < 0.001, Kruskal
      Wallis test). LSCM demonstrated no differences between SSI and SSII (Mann-Whitney
      U test). Compared with control subjects, SS subjects' MGs showed more
      periglandular inflammation and higher secretion reflectivity (P < 0.001, Mann
      Whitney U test). Compared with MGD patients, SS patients' MGs had higher acinar
      density, smaller diameters, greater density of periglandular inflammatory cells,
      and lower secretion reflectivity (P < 0.001, Mann-Whitney U test). In SS
      patients, the two measured confocal signs of inflammation were significantly
      interrelated and correlated with corneal fluorescein staining (P <= 0.01,
      Spearman correlation coefficient). Acinar density and diameters were strongly
      correlated among themselves (P < 0.001) and with BUT (P < 0.05). CONCLUSIONS:
      LSCM is capable of effectively revealing morphologic and inflammatory changes in
      MGs and showed discernible patterns of MG abnormalities in SS and MGD not easily
      distinguishable by the usual clinical exams.

PMID- 21169535
TI  - United healthcare, five oncology practices try bundled payments.

PMID- 21169537
TI  - Supportive care: large studies ease yoga, exercise into mainstream oncology.

PMID- 21169538
TI  - Inference from a multiplicative model of joint genetic effects for [corrected]
      ovarian cancer risk.

PMID- 21169539
TI  - StatBite Proportion of U.S. Expenditures for Cancer Care by Phase of Care.

PMID- 21169540
TI  - Beyond FDG: Many Molecular Imaging Agents Are in Development.

PMID- 21169541
TI  - Cutting edge: crucial role of IL-1 and IL-23 in the innate IL-17 response of
      peripheral lymph node NK1.1- invariant NKT cells to bacteria.
AB  - We have shown previously that peripheral lymph node-resident retinoic acid
      receptor-related orphan receptor gammat(+) NK1.1(-) invariant NKT (iNKT) cells
      produce IL-17A independently of IL-6. In this study, we show that the concomitant
      presence of IL-1 and IL-23 is crucial to induce a rapid and sustained IL-17A/F
      and IL-22 response by these cells that requires TCR-CD1d interaction and partly
      relies on IL-23-mediated upregulation of IL-23R and IL-1R1 expression. We further
      show that IL-1 and IL-23 produced by pathogen-associated molecular pattern
      stimulated dendritic cells induce this response from NK1.1(-) iNKT cells in
      vitro, involving mainly TLR2/4-signaling pathways. Finally, we found that IL-17A
      production by these cells occurs very early and transiently in vivo in response
      to heat-killed bacteria. Overall, our study indicates that peripheral lymph node
      NK1.1(-) iNKT cells could be a source of innate Th17-related cytokines during
      bacterial infections and supports the hypothesis that they are able to provide an
      efficient first line of defense against bacterial invasion.

PMID- 21169536
TI  - Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation
      carriers.
AB  - BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes are associated with
      increased risks of breast and ovarian cancers. Although several common variants
      have been associated with breast cancer susceptibility in mutation carriers, none
      have been associated with ovarian cancer susceptibility. A genome-wide
      association study recently identified an association between the rare allele of
      the single-nucleotide polymorphism (SNP) rs3814113 (ie, the C allele) at 9p22.2
      and decreased risk of ovarian cancer for women in the general population. We
      evaluated the association of this SNP with ovarian cancer risk among BRCA1 or
      BRCA2 mutation carriers by use of data from the Consortium of Investigators of
      Modifiers of BRCA1/2. METHODS: We genotyped rs3814113 in 10,029 BRCA1 mutation
      carriers and 5837 BRCA2 mutation carriers. Associations with ovarian and breast
      cancer were assessed with a retrospective likelihood approach. All statistical
      tests were two-sided. RESULTS: The minor allele of rs3814113 was associated with
      a reduced risk of ovarian cancer among BRCA1 mutation carriers (per-allele hazard
      ratio of ovarian cancer = 0.78, 95% confidence interval = 0.72 to 0.85; P = 4.8 *
      10(-9)) and BRCA2 mutation carriers (hazard ratio of ovarian cancer = 0.78, 95%
      confidence interval = 0.67 to 0.90; P = 5.5 * 10(-4)). This SNP was not
      associated with breast cancer risk among either BRCA1 or BRCA2 mutation carriers.
      BRCA1 mutation carriers with the TT genotype at SNP rs3814113 were predicted to
      have an ovarian cancer risk to age 80 years of 48%, and those with the CC
      genotype were predicted to have a risk of 33%. CONCLUSION: Common genetic
      variation at the 9p22.2 locus was associated with decreased risk of ovarian
      cancer for carriers of a BRCA1 or BRCA2 mutation.

PMID- 21169542
TI  - Elevated proinflammatory cytokine production by a skewed T cell compartment
      requires monocytes and promotes inflammation in type 2 diabetes.
AB  - An appropriate balance between proinflammatory (Th17 and Th1) and anti
      inflammatory (regulatory T cells [Tregs] and Th2) subsets of T cells is critical
      to maintain homeostasis and avoid inflammatory disease. Type 2 diabetes (T2D) is
      a chronic inflammatory disease promoted by changes in immune cell function.
      Recent work indicates T cells are important mediators of inflammation in a mouse
      model of T2D. These studies identified an elevation in the Th17 and Th1 subsets
      with a decrease in the Treg subset, which culminates in inflammation and insulin
      resistance. Based on these data, we tested the hypothesis that T cells in T2D
      patients are skewed toward proinflammatory subsets. Our data show that blood from
      T2D patients has increased circulating Th17 cells and elevated activation of Th17
      signature genes. Importantly, T cells required culture with monocytes to maintain
      Th17 signatures, and fresh ex vivo T cells from T2D patients appeared to be
      poised for IL-17 production. T cells from T2D patients also have increased
      production of IFN-gamma, but produce healthy levels of IL-4. In contrast, T2D
      patients had decreased percentages of CD4(+) Tregs. These data indicate that T
      cells in T2D patients are naturally skewed toward proinflammatory subsets that
      likely promote chronic inflammation in T2D through elevated cytokine production.
      Potential therapies targeted toward resetting this balance need to be approached
      with caution due to the reciprocal relationship between Th17 cells and Tregs.
      Understanding the unique aspects of T2D T cells is essential to predict outcomes
      of such treatments.

PMID- 21169544
TI  - Genome-based in silico identification of new Mycobacterium tuberculosis antigens
      activating polyfunctional CD8+ T cells in human tuberculosis.
AB  - Although CD8(+) T cells help control Mycobacterium tuberculosis infection, their
      M. tuberculosis Ag repertoire, in vivo frequency, and functionality in human
      tuberculosis (TB) remains largely undefined. We have performed genome-based
      bioinformatics searches to identify new M. tuberculosis epitopes presented by
      major HLA class I supertypes A2, A3, and B7 (covering 80% of the human
      population). A total of 432 M. tuberculosis peptides predicted to bind to HLA
      A*0201, HLA-A*0301, and HLA-B*0702 (representing the above supertypes) were
      synthesized and HLA-binding affinities determined. Peptide-specific CD8(+) T cell
      proliferation assays (CFSE dilution) in 41 M. tuberculosis-responsive donors
      identified 70 new M. tuberculosis epitopes. Using HLA/peptide tetramers for the
      18 most prominently recognized HLA-A*0201-binding M. tuberculosis peptides,
      recognition by cured TB patients' CD8(+) T cells was validated for all 18
      epitopes. Intracellular cytokine staining for IFN-gamma, IL-2, and TNF-alpha
      revealed mono-, dual-, as well as triple-positive CD8(+) T cells, indicating
      these M. tuberculosis peptide-specific CD8(+) T cells were (poly)functional.
      Moreover, these T cells were primed during natural infection, because they were
      absent from M. tuberculosis-noninfected individuals. Control CMV peptide/HLA
      A*0201 tetramers stained CD8(+) T cells in M. tuberculosis-infected and
      noninfected individuals equally, whereas Ebola peptide/HLA-A*0201 tetramers were
      negative. In conclusion, the M. tuberculosis-epitope/Ag repertoire for human
      CD8(+) T cells is much broader than hitherto suspected, and the newly identified
      M. tuberculosis Ags are recognized by (poly)functional CD8(+) T cells during
      control of infection. These results impact on TB-vaccine design and biomarker
      identification.

PMID- 21169545
TI  - IL-21 receptor is critical for the development of memory B cell responses.
AB  - Development of long-term humoral immunity, characterized by the formation of long
      lived plasma cells (PCs) in the bone marrow and memory B cells, is a critical
      component of protective immunity to pathogens, and as such it is the major goal
      of vaccination. However, the mechanisms involved in the generation of long-term
      humoral immunity remain poorly understood. In this study, we used IL-21R
      deficient (IL-21R.KO) mice to examine the role of the IL-21 pathway in the
      development of the B cell memory response. Primary IgG serum Ab responses to the
      T cell-dependent Ag 4-hydroxy-3-nitrophenylacetyl (NP) hapten conjugated to
      chicken gamma globulin were delayed in IL-21R.KO mice, but reached normal titers
      within 3 to 4 wk of immunization. IL-21R.KO mice formed germinal centers and
      generated normal numbers of PCs in their bone marrow. Additionally, memory B cell
      formation was similar in wild-type and IL-21R.KO mice. However, NP-specific
      memory B cells and PCs failed to expand following secondary immunization of IL
      21R.KO mice, and consequently, secondary IgG Ab responses to NP hapten conjugated
      to chicken gamma globulin were significantly impaired. These results identify the
      IL-21 pathway as a critical component of the memory B cell response.

PMID- 21169543
TI  - IL-2-controlled expression of multiple T cell trafficking genes and Th2 cytokines
      in the regulatory T cell-deficient scurfy mice: implication to multiorgan
      inflammation and control of skin and lung inflammation.
AB  - Scurfy (Sf) mice bear a mutation in the Foxp3 transcription factor, lack
      regulatory T cells (Treg), develop multiorgan inflammation, and die prematurely.
      The major target organs affected are skin, lungs, and liver. "Sf mice lacking the
      Il2 gene (Sf.Il2-/-), despite being devoid of Treg, did not develop skin and lung
      inflammation, but the inflammation in liver remained [corrected]. Genome-wide
      microarray analysis revealed hundreds of genes that were differentially regulated
      among Sf, Sf.Il2(-/-), and B6 CD4(+) T cells, but the most significant changes
      were those encoding receptors for trafficking/chemotaxis/retention and cytokines.
      Our study suggests that IL-2 controls the skin and lung inflammation in Sf mice
      in an apparent "organ-specific" manner through two novel mechanisms: by
      regulating the expression of genes encoding a variety of receptors for T cell
      trafficking/chemotaxis/retention and by regulating Th2 cell expansion and
      cytokine production. Thus, IL-2 is potentially a master regulator for multiorgan
      inflammation and an underlying etiological factor for various diseases associated
      with skin and lung inflammation.

PMID- 21169546
TI  - Systemic immunological tolerance to ocular antigens is mediated by TRAIL
      expressing CD8+ T cells.
AB  - Systemic immunological tolerance to Ag encountered in the eye restricts the
      formation of potentially damaging immune responses that would otherwise be
      initiated at other anatomical locations. We previously demonstrated that
      tolerance to Ag administered via the anterior chamber (AC) of the eye required
      Fas ligand-mediated apoptotic death of inflammatory cells that enter the eye in
      response to the antigenic challenge. Moreover, the systemic tolerance induced
      after AC injection of Ag was mediated by CD8(+) regulatory T cells. This study
      examined the mechanism by which these CD8(+) regulatory T cells mediate tolerance
      after AC injection of Ag. AC injection of Ag did not prime CD4(+) T cells and led
      to increased TRAIL expression by splenic CD8(+) T cells. Unlike wild-type mice,
      Trail(-/-) or Dr5(-/-) mice did not develop tolerance to Ag injected into the
      eye, even though responding lymphocytes underwent apoptosis in the AC of the eyes
      of these mice. CD8(+) T cells from Trail(-/-) mice that were first injected via
      the AC with Ag were unable to transfer tolerance to naive recipient wild-type
      mice, but CD8(+) T cells from AC-injected wild-type or Dr5(-/-) mice could
      transfer tolerance. Importantly, the transferred wild-type (Trail(+/+)) CD8(+) T
      cells were also able to decrease the number of infiltrating inflammatory cells
      into the eye; however, Trail(-/-) CD8(+) T cells were unable to limit the
      inflammatory cell ingress. Together, our data suggest that "helpless" CD8(+)
      regulatory T cells generated after AC injection of Ag enforce systemic tolerance
      in a TRAIL-dependent manner to inhibit inflammation in the eye.

PMID- 21169548
TI  - Universal vaccine based on ectodomain of matrix protein 2 of influenza A: Fc
      receptors and alveolar macrophages mediate protection.
AB  - The ectodomain of matrix protein 2 (M2e) of influenza A virus is an attractive
      target for a universal influenza A vaccine: the M2e sequence is highly conserved
      across influenza virus subtypes, and induced humoral anti-M2e immunity protects
      against a lethal influenza virus challenge in animal models. Clinical phase I
      studies with M2e vaccine candidates have been completed. However, the in vivo
      mechanism of immune protection induced by M2e-carrier vaccination is unclear.
      Using passive immunization experiments in wild-type, FcRgamma(-/-), FcgammaRI(-/
      ), FcgammaRIII(-/-), and (FcgammaRI, FcgammaRIII)(-/-) mice, we report in this
      study that Fc receptors are essential for anti-M2e IgG-mediated immune
      protection. M2e-specific IgG1 isotype Abs are shown to require functional
      FcgammaRIII for in vivo immune protection but other anti-M2e IgG isotypes can
      rescue FcgammaRIII(-/-) mice from a lethal challenge. Using a conditional cell
      depletion protocol, we also demonstrate that alveolar macrophages (AM) play a
      crucial role in humoral M2e-specific immune protection. Additionally, we show
      that adoptive transfer of wild-type AM into (FcgammaRI, FcgammaRIII)(-/-) mice
      restores protection by passively transferred anti-M2e IgG. We conclude that AM
      and Fc receptor-dependent elimination of influenza A virus-infected cells are
      essential for protection by anti-M2e IgG.

PMID- 21169547
TI  - Bacterial lipoprotein TLR2 agonists broadly modulate endothelial function and
      coagulation pathways in vitro and in vivo.
AB  - TLR2 activation induces cellular and organ inflammation and affects lung
      function. Because deranged endothelial function and coagulation pathways
      contribute to sepsis-induced organ failure, we studied the effects of bacterial
      lipoprotein TLR2 agonists, including peptidoglycan-associated lipoprotein,
      Pam3Cys, and murein lipoprotein, on endothelial function and coagulation pathways
      in vitro and in vivo. TLR2 agonist treatment induced diverse human endothelial
      cells to produce IL-6 and IL-8 and to express E-selectin on their surface,
      including HUVEC, human lung microvascular endothelial cells, and human coronary
      artery endothelial cells. Treatment of HUVEC with TLR2 agonists caused increased
      monolayer permeability and had multiple coagulation effects, including increased
      production of plasminogen activator inhibitor-1 (PAI-1) and tissue factor, as
      well as decreased production of tissue plasminogen activator and tissue factor
      pathway inhibitor. TLR2 agonist treatment also increased HUVEC expression of TLR2
      itself. Peptidoglycan-associated lipoprotein induced IL-6 production by
      endothelial cells from wild-type mice but not from TLR2 knockout mice, indicating
      TLR2 specificity. Mice were challenged with TLR2 agonists, and lungs and plasmas
      were assessed for markers of leukocyte trafficking and coagulopathy. Wild-type
      mice, but not TLR2 mice, that were challenged i.v. with TLR2 agonists had
      increased lung levels of myeloperoxidase and mRNAs for E-selectin, P-selectin,
      and MCP-1, and they had increased plasma PAI-1 and E-selectin levels.
      Intratracheally administered TLR2 agonist caused increased lung fibrin levels.
      These studies show that TLR2 activation by bacterial lipoproteins broadly affects
      endothelial function and coagulation pathways, suggesting that TLR2 activation
      contributes in multiple ways to endothelial activation, coagulopathy, and
      vascular leakage in sepsis.

PMID- 21169549
TI  - Macrophage migration inhibitory factor counterregulates dexamethasone-mediated
      suppression of hypoxia-inducible factor-1 alpha function and differentially
      influences human CD4+ T cell proliferation under hypoxia.
AB  - Hypoxia, a feature of inflammation and tumors, is a potent inducer of the
      proinflammatory cytokine macrophage migration inhibitory factor (MIF). In
      transformed cells, MIF was shown to modulate and to be modulated via the oxygen
      sensitive transcription factor hypoxia-inducible factor (HIF)-1. Furthermore,
      anti-inflammatory glucocorticoids (GCs) were described to regulate MIF action.
      However, in-depth studies of the interaction between MIF and HIF-1 and GC action
      in nontransformed primary human CD4(+) T cells under hypoxia are missing.
      Therefore, we investigated the functional relationship between MIF and HIF and
      the impact of the GC dexamethasone (DEX) on these key players of inflammation in
      human CD4(+) T cells. In this article, we show that hypoxia, and specifically HIF
      1, is a potent and rapid inducer of MIF expression in primary human CD4(+) T
      cells, as well as in Jurkat T cells. MIF signaling via CD74, in turn, is
      essential for hypoxia-mediated HIF-1alpha expression and HIF-1 target gene
      induction involving ERK/mammalian target of rapamycin activity complemented by
      PI3K activation upon mitogen stimulation. Furthermore, MIF signaling enhances T
      cell proliferation under normoxia but not hypoxia. MIF also counterregulates DEX
      mediated suppression of MIF and HIF-1alpha expression. Based on these data, we
      suggest that hypoxia significantly affects the expression of HIF-1alpha in a MIF
      dependent manner leading to a positive-feedback loop in primary human CD4(+) T
      cells, thus influencing the lymphoproliferative response and DEX action via the
      GC receptor. Therefore, we suggest that HIF and/or MIF could be useful targets to
      optimize GC therapy when treating inflammation.

PMID- 21169550
TI  - Lactobacillus-mediated priming of the respiratory mucosa protects against lethal
      pneumovirus infection.
AB  - The inflammatory response to respiratory virus infection can be complex and
      refractory to standard therapy. Lactobacilli, when targeted to the respiratory
      epithelium, are highly effective at suppressing virus-induced inflammation and
      protecting against lethal disease. Specifically, wild-type mice primed via
      intranasal inoculation with live or heat-inactivated Lactobacillus plantarum or
      Lactobacillus reuteri were completely protected against lethal infection with the
      virulent rodent pathogen, pneumonia virus of mice; significant protection (60%
      survival) persisted for at least 13 wk. Protection was not unique to
      Lactobacillus species, and it was also observed in response to priming with
      nonpathogenic Gram-positive Listeria innocua. Priming with live lactobacilli
      resulted in diminished granulocyte recruitment, diminished expression of multiple
      proinflammatory cytokines (CXCL10, CXCL1, CCL2, and TNF), and reduced virus
      recovery, although we have demonstrated clearly that absolute virus titer does
      not predict clinical outcome. Lactobacillus priming also resulted in prolonged
      survival and protection against the lethal sequelae of pneumonia virus of mice
      infection in MyD88 gene-deleted (MyD88(-/-)) mice, suggesting that the protective
      mechanisms may be TLR-independent. Most intriguing, virus recovery and cytokine
      expression patterns in Lactobacillus-primed MyD88(-/-) mice were
      indistinguishable from those observed in control-primed MyD88(-/-) counterparts.
      In summary, we have identified and characterized an effective Lactobacillus
      mediated innate immune shield, which may ultimately serve as critical and long
      term protection against infection in the absence of specific antiviral vaccines.

PMID- 21169551
TI  - Natural forms of vitamin E and 13'-carboxychromanol, a long-chain vitamin E
      metabolite, inhibit leukotriene generation from stimulated neutrophils by
      blocking calcium influx and suppressing 5-lipoxygenase activity, respectively.
AB  - Leukotrienes generated by 5-lipoxygenase (5-LOX)-catalyzed reaction are key
      regulators of inflammation. In ionophore-stimulated (A23187; 1-2.5 MUM) human
      blood neutrophils or differentiated HL-60 cells, vitamin E forms differentially
      inhibited leukotriene B(4) (LTB(4)) with an IC(50) of 5-20 MUM for gamma
      tocopherol, delta-tocopherol (deltaT), and gamma-tocotrienol, but a much higher
      IC(50) for alpha-tocopherol. 13'-Carboxychromanol, a long-chain metabolite of
      deltaT, suppressed neutrophil- and HL-60 cell-generated LTB(4) with an IC(50) of
      4-7 MUM and potently inhibited human recombinant 5-LOX activity with an IC(50) of
      0.5-1 MUM. In contrast, vitamin E forms had no effect on human 5-LOX activity but
      impaired ionophore-induced intracellular calcium increase and calcium influx as
      well as the subsequent signaling including ERK1/2 phosphorylation and 5-LOX
      translocation from cytosol to the nucleus, a key event for 5-LOX activation.
      Further investigation showed that deltaT suppressed cytosolic Ca(2+) increase
      and/or LTB(4) formation triggered by ionophores, sphingosine 1-phosphate, and
      lysophosphatidic acid but not by fMLP or thapsigargin, whereas 13'
      carboxychromanol decreased cellular production of LTB(4) regardless of different
      stimuli, consistent with its strong inhibition of the 5-LOX activity. These
      observations suggest that deltaT does not likely affect fMLP receptor-mediated
      signaling or store depletion-induced calcium entry. Instead, we found that deltaT
      prevented ionophore-caused cytoplasmic membrane disruption, which may account for
      its blocking of calcium influx. These activities by vitamin E forms and long
      chain carboxychromanol provide potential molecular bases for the differential
      anti-inflammatory effects of vitamin E forms in vivo.

PMID- 21169552
TI  - Oxidized cellulose binding to allergens with a carbohydrate-binding module
      attenuates allergic reactions.
AB  - Grass and mite allergens are of the main causes of allergy and asthma. A
      carbohydrate-binding module (CBM) represents a common motif to groups I (beta
      expansin) and II/III (expansin-like) grass allergens and is suggested to mediate
      allergen-IgE binding. House dust mite group II allergen (Der p 2 and Der f 2)
      structures bear strong similarity to expansin's CBM, suggesting their ability to
      bind carbohydrates. Thus, this study proposes the design of a carbohydrate-based
      treatment in which allergen binding to carbohydrate particles will promote
      allergen airway clearance and prevent allergic reactions. The aim of the study
      was to identify a polysaccharide with high allergen-binding capacities and to
      explore its ability to prevent allergy. Oxidized cellulose (OC) demonstrated
      allergen-binding capacities toward grass and mite allergens that surpassed those
      of any other polysaccharide examined in this study. Furthermore, inhalant
      preparations of OC microparticles attenuated allergic lung inflammation in rye
      grass-sensitized Brown Norway rats and OVA-sensitized BALB/c mice. Fluorescently
      labeled OC efficiently cleared from the mouse airways and body organs. Moreover,
      long-term administration of OC inhalant to Wistar rats did not result in
      toxicity. In conclusion, many allergens, such as grass and dust mite, contain a
      common CBM motif. OC demonstrates a strong and relatively specific allergen
      binding capacity to CBM-containing allergens. OC's ability to attenuate allergic
      inflammation, together with its documented safety record, forms a firm basis for
      its application as an alternative treatment for prevention and relief of allergy
      and asthma.

PMID- 21169553
TI  - CD8 T cells mediate direct biliary ductule damage in nonobese diabetic autoimmune
      biliary disease.
AB  - We previously described the NOD.c3c4 mouse, which is protected from type 1
      diabetes (T1D) because of protective alleles at multiple insulin-dependent
      diabetes (Idd) genes, but develops autoimmune biliary disease (ABD) resembling
      primary biliary cirrhosis (PBC). In this paper, we characterize the NOD.ABD
      strain, which is genetically related to the NOD.c3c4 strain but develops both ABD
      and T1D. Histologically, NOD.ABD biliary disease is indistinguishable from that
      in NOD.c3c4 mice. The frequency of effector memory (CD44(+)CD62L(-)) and central
      memory (CD44(+)CD62L(+)) CD8 T cells is significantly increased in the
      intrahepatic lymphocyte fraction of NOD.ABD mice, and NOD.ABD CD8 T cells produce
      more IFN-gamma and TNF-alpha, compared with controls. NOD.ABD splenocytes can
      transfer ABD and T1D to NOD.c3c4 scid mice, but only T1D to NOD scid mice,
      suggesting that the genetic origin of the target organ and/or its innate immune
      cells is critical to disease pathogenesis. The disease transfer model,
      importantly, shows that biliary duct damage (characteristic of PBC) and
      inflammation precede biliary epithelial cell proliferation. Unlike T1D where both
      CD4 and CD8 T cells are required for disease transfer, purified NOD.ABD CD8 T
      cells can transfer liver inflammation into NOD.c3c4 scid recipients, and disease
      transfer is ameliorated by cotransferring T regulatory cells. Unlike NOD.c3c4
      mice, NOD.ABD mice do not develop anti-nuclear or anti-Smith autoantibodies;
      however, NOD.ABD mice do develop the antipyruvate dehydrogenase Abs typical of
      human PBC. The NOD.ABD strain is a model of immune dysregulation affecting two
      organ systems, most likely by mechanisms that do not completely coincide.

PMID- 21169554
TI  - Structure-function relations in an elastase-induced mouse model of emphysema.
AB  - Emphysema is a progressive disease characterized by the destruction of peripheral
      airspaces and subsequent decline in lung function. However, the relation between
      structure and function during disease progression is not well understood. The
      objective of this study was to assess the time course of the structural,
      mechanical, and remodeling properties of the lung in mice after elastolytic
      injury. At 2, 7, and 21 days after treatment with porcine pancreatic elastase,
      respiratory impedance, the constituents of lung extracellular matrix, and
      histological sections of the lung were evaluated. In the control group, no
      changes were observed in the structural or functional properties, whereas, in the
      treatment group, the respiratory compliance and its variability significantly
      increased by Day 21 (P < 0.001), and the difference in parameters decreased with
      increasing positive end-expiratory pressure. The heterogeneity of airspace
      structure gradually increased over time. Conversely, the relative amounts of
      elastin and type I collagen exhibited a peak (P < 0.01) at Day 2, but returned to
      baseline levels by Day 21. Structure-function relations manifested themselves in
      strong correlations between compliance parameters and both mean size and
      heterogeneity of airspace structure (r(2) > 0.9). Similar relations were also
      obtained in a network model of the parenchyma in which destruction was based on
      the notion that mechanical forces contribute to alveolar wall rupture. We
      conclude that, in a mouse model of emphysema, progressive decline in lung
      function is sensitive to the development of airspace heterogeneity governed by
      local, mechanical, force-induced failure of remodeled collagen.

PMID- 21169556
TI  - Acute lung injury induces cardiovascular dysfunction: effects of IL-6 and
      budesonide/formoterol.
AB  - Acute lung injury (ALI) is associated with systemic inflammation and
      cardiovascular dysfunction. IL-6 is a biomarker of this systemic response and a
      predictor of cardiovascular events, but its possible causal role is uncertain.
      Inhaled corticosteroids and long-acting beta2 agonists (ICS/LABA) down-regulate
      the systemic expression of IL-6, but whether they can ameliorate the
      cardiovascular dysfunction related to ALI is uncertain. We sought to determine
      whether IL-6 contributes to the cardiovascular dysfunction related to ALI, and
      whether budesonide/formoterol ameliorates this process. Wild-type mice were
      pretreated for 3 hours with intratracheal budesonide, formoterol, or both, before
      LPS was sprayed into their tracheas. IL-6-deficient mice were similarly exposed
      to LPS. Four hours later, bronchoalveolar lavage fluid (BALF) and serum were
      collected, and endothelial and cardiac functions were measured, using wire
      myography of the aortic tissue and echocardiography, respectively. LPS
      significantly impaired vasodilatory responses to acetylcholine (P < 0.001) and
      cardiac output (P = 0.002) in wild-type but not IL-6-deficient mice.
      Intratracheal instillations of exogenous IL-6 into IL-6-deficient mice restored
      these impairments (vasodilatory responses to acetylcholine, P = 0.005; cardiac
      output, P = 0.025). Pretreatment with the combination of budesonide and
      formoterol, but not either alone, ameliorated the vasodilatory responses to
      acetylcholine (P = 0.018) and cardiac output (P < 0.001). These drugs also
      attenuated the rise in the systemic expression of IL-6 (P < 0.05) related to LPS.
      IL-6 contributes to the cardiovascular dysfunction related to LPS, and
      pretreatment with budesonide/formoterol reduces the systemic expression of IL-6
      and improves cardiovascular dysfunction. ICS/LABA may reduce acute cardiovascular
      events related to ALI.

PMID- 21169555
TI  - Role of endoplasmic reticulum stress in epithelial-mesenchymal transition of
      alveolar epithelial cells: effects of misfolded surfactant protein.
AB  - Endoplasmic reticulum (ER) stress has been implicated in alveolar epithelial type
      II (AT2) cell apoptosis in idiopathic pulmonary fibrosis. We hypothesized that ER
      stress (either chemically induced or due to accumulation of misfolded proteins)
      is also associated with epithelial-mesenchymal transition (EMT) in alveolar
      epithelial cells (AECs). ER stress inducers, thapsigargin (TG) or tunicamycin
      (TN), increased expression of ER chaperone, Grp78, and spliced X-box binding
      protein 1, decreased epithelial markers, E-cadherin and zonula occludens-1 (ZO
      1), increased the myofibroblast marker, alpha-smooth muscle actin (alpha-SMA),
      and induced fibroblast-like morphology in both primary AECs and the AT2 cell
      line, RLE-6TN, consistent with EMT. Overexpression of the surfactant protein (SP)
      C BRICHOS mutant SP-C(DeltaExon4) in A549 cells increased Grp78 and alpha-SMA and
      disrupted ZO-1 distribution, and, in primary AECs, SP-C(DeltaExon4) induced
      fibroblastic-like morphology, decreased ZO-1 and E-cadherin and increased alpha
      SMA, mechanistically linking ER stress associated with mutant SP to fibrosis
      through EMT. Whereas EMT was evident at lower concentrations of TG or TN, higher
      concentrations caused apoptosis. The Src inhibitor, 4-amino-5-(4-chlorophenyl)-7
      (t-butyl)pyrazolo[3,4]pyramidine) (PP2), abrogated EMT associated with TN or TG
      in primary AECs, whereas overexpression of SP-C(DeltaExon4) increased Src
      phosphorylation, suggesting a common mechanism. Furthermore, increased Grp78
      immunoreactivity was observed in AT2 cells of mice after bleomycin injury,
      supporting a role for ER stress in epithelial abnormalities in fibrosis in vivo.
      These results demonstrate that ER stress induces EMT in AECs, at least in part
      through Src-dependent pathways, suggesting a novel role for ER stress in
      fibroblast accumulation in pulmonary fibrosis.

PMID- 21169557
TI  - Recruitment of dynein to late endosomes and lysosomes through light intermediate
      chains.
AB  - Cytoplasmic dynein is involved in a wide range of cellular processes, but how it
      is regulated and how it recognizes an extremely wide range of cargo are
      incompletely understood. The dynein light intermediate chains, LIC1 and LIC2
      (DYNC1LI1 and DYNC1LI2, respectively), have been implicated in cargo binding, but
      their full range of functions is unknown. Using LIC isoform-specific antibodies,
      we report the first characterization of their subcellular distribution and
      identify a specific association with elements of the late endocytic pathway, but
      not other vesicular compartments. LIC1 and LIC2 RNA interference (RNAi) each
      specifically disrupts the distribution of lysosomes and late endosomes.
      Stimulation of dynein-mediated late-endosomal transport by the Rab7-interacting
      lysosomal protein (RILP) is reversed by LIC1 RNAi, which displaces dynein, but
      not dynactin, from these structures. Conversely, expression of DeltaN-RILP or the
      dynactin subunit dynamitin each fails to displace dynein, but not dynactin. Thus,
      using a variety of complementary approaches, our results indicate a novel
      specific role for the LICs in dynein recruitment to components of the late
      endocytic pathway.

PMID- 21169558
TI  - Huntingtin coordinates the dynein-mediated dynamic positioning of endosomes and
      lysosomes.
AB  - Huntingtin (Htt) is a membrane-associated scaffolding protein that interacts with
      microtubule motors as well as actin-associated adaptor molecules. We examined a
      role for Htt in the dynein-mediated intracellular trafficking of endosomes and
      lysosomes. In HeLa cells depleted of either Htt or dynein, early, recycling, and
      late endosomes (LE)/lysosomes all become dispersed. Despite altered organelle
      localization, kinetic assays indicate only minor defects in intracellular
      trafficking. Expression of full-length Htt is required to restore organelle
      localization in Htt-depleted cells, supporting a role for Htt as a scaffold that
      promotes functional interactions along its length. In dynein-depleted cells,
      LE/lysosomes accumulate in tight patches near the cortex, apparently enmeshed by
      cortactin-positive actin filaments; Latrunculin B-treatment disperses these
      patches. Peripheral LE/lysosomes in dynein-depleted cells no longer colocalize
      with microtubules. Htt may be required for this off-loading, as the loss of
      microtubule association is not seen in Htt-depleted cells or in cells depleted of
      both dynein and Htt. Inhibition of kinesin-1 relocalizes peripheral LE/lysosomes
      induced by Htt depletion but not by dynein depletion, consistent with their
      detachment from microtubules upon dynein knockdown. Together, these data support
      a model of Htt as a facilitator of dynein-mediated trafficking that may regulate
      the cytoskeletal association of dynamic organelles.

PMID- 21169559
TI  - Disruption of PKB signaling restores polarity to cells lacking tumor suppressor
      PTEN.
AB  - By limiting phosphotidylinositol 3,4,5-triphosphate (PIP(3)) levels, tumor
      suppressor PTEN not only controls cell growth but also maintains cell polarity
      required for cytokinesis and chemotaxis. To identify the critical targets of
      PIP(3) that link it to the cytoskeleton, we deleted secondary genes to reverse
      the deficiencies of pten- cells in Dictyostelium. The polarity defects in pten-
      cells correlate with elevated phosphorylations of PKB substrates. Deletion of AKT
      orthologue, PkbA, or a subunit of its activator TORC2, reduced the
      phosphorylations and suppressed the cytokinesis and chemotaxis defects in pten-
      cells. In these double mutants, the excessive PIP(3) levels and, presumably,
      activation of other PIP(3)-binding proteins had little or no effect on the
      cytoskeleton. In bands with increased phosphorylation in pten- cells, we found
      PKB substrates, PI5K, GefS, GacG, and PakA. Disruption of PakA in pten- cells
      restored a large fraction of the cells to normal behavior. Consistently,
      expression of phosphomimetic PakA in pten- cells exacerbated the defects but
      nonphosphorylatable PakA had no effect. Thus, among many putative PTEN- and
      PIP(3)-dependent events, phosphorylation of PKB substrates is the key downstream
      regulator of cell polarity.

PMID- 21169560
TI  - Constitutive activated Cdc42-associated kinase (Ack) phosphorylation at arrested
      endocytic clathrin-coated pits of cells that lack dynamin.
AB  - Clathrin-mediated endocytosis is a fundamental cellular process conserved from
      yeast to mammals and is an important endocytic route for the internalization of
      many specific cargos, including activated growth factor receptors. Here we
      examined changes in tyrosine phosphorylation, a representative output of growth
      factor receptor signaling, in cells in which endocytic clathrin-coated pits are
      frozen at a deeply invaginated state, that is, cells that lack dynamin
      (fibroblasts from dynamin 1, dynamin 2 double conditional knockout mice). The
      major change observed in these cells relative to wild-type cells was an increase
      in the phosphorylation state, and thus activation, of activated Cdc42-associated
      kinase (Ack), a nonreceptor tyrosine kinase. Ack is concentrated at clathrin
      coated pits, and binds clathrin heavy chain via two clathrin boxes. RNA
      interference-based approaches and pharmacological manipulations further
      demonstrated that the phosphorylation of Ack requires both clathrin assembly into
      endocytic clathrin-coated pits and active Cdc42. These findings reveal a link
      between progression of clathrin-coated pits to endocytic vesicles and an
      activation-deactivation cycle of Ack.

PMID- 21169561
TI  - Role of Pax3 acetylation in the regulation of Hes1 and Neurog2.
AB  - Pax3 plays a role in regulating Hes1 and Neurog2 activity and thereby stem cell
      maintenance and neurogenesis. A mechanism for Pax3 regulation of these two
      opposing events, during caudal neural tube development, is examined in this
      study. Pax3 acetylation on C-terminal lysine residues K437 and K475 may be
      critical for proper regulation of Hes1 and Neurog2. Removal of these lysine
      residues increased Hes1 but decreased Neurog2 promoter activity. SIRT1
      deacetylase may be a key component in regulating Pax3 acetylation. Chromatin
      immunoprecipitation assays showed that SIRT1 is associated with Hes1 and Neurog2
      promoters during murine embryonic caudal neural tube development at E9.5, but not
      at E12.5. Overexpression of SIRT1 decreased Pax3 acetylation, Neurog2 and Brn3a
      positive staining. Conversely, siRNA-mediated silencing of SIRT1 increased these
      factors. These studies suggest that Pax3 acetylation results in decreased Hes1
      and increased Neurog2 activity, thereby promoting sensory neuron differentiation.

PMID- 21169562
TI  - The Dam1 ring binds to the E-hook of tubulin and diffuses along the microtubule.
AB  - There has been much effort in recent years aimed at understanding the molecular
      mechanism by which the Dam1 kinetochore complex is able to couple microtubule
      depolymerization to poleward movement. Both a biased diffusion and a forced walk
      model have been proposed, and several key functional aspects of Dam1-microtubule
      binding are disputed. Here, we investigate the elements involved in tubulin-Dam1
      complex interactions and directly visualize Dam1 rings on microtubules in order
      to infer their dynamic behavior on the microtubule lattice and its likely
      relevance at the kinetochore. We find that the Dam1 complex has a preference for
      native tubulin over tubulin that is lacking its acidic C-terminal tail.
      Statistical mechanical analysis of images of Dam1 rings on microtubules, applied
      to both the distance between rings and the tilt angle of the rings with respect
      to the microtubule axis, supports a diffusive ring model. We also present a cryo
      EM reconstruction of the Dam1 ring, likely the relevant assembly form of the
      complex for energy coupling during microtubule depolymerization in budding yeast.
      The present studies constitute a significant step forward by linking structural
      and biochemical observations toward a comprehensive understanding of the Dam1
      complex.

PMID- 21169563
TI  - The steady-state repertoire of human SCF ubiquitin ligase complexes does not
      require ongoing Nedd8 conjugation.
AB  - The human genome encodes 69 different F-box proteins (FBPs), each of which can
      potentially assemble with Skp1-Cul1-RING to serve as the substrate specificity
      subunit of an SCF ubiquitin ligase complex. SCF activity is switched on by
      conjugation of the ubiquitin-like protein Nedd8 to Cul1. Cycles of Nedd8
      conjugation and deconjugation acting in conjunction with the Cul1-sequestering
      factor Cand1 are thought to control dynamic cycles of SCF assembly and
      disassembly, which would enable a dynamic equilibrium between the Cul1-RING
      catalytic core of SCF and the cellular repertoire of FBPs. To test this
      hypothesis, we determined the cellular composition of SCF complexes and evaluated
      the impact of Nedd8 conjugation on this steady-state. At least 42 FBPs assembled
      with Cul1 in HEK 293 cells, and the levels of Cul1-bound FBPs varied by over two
      orders of magnitude. Unexpectedly, quantitative mass spectrometry revealed that
      blockade of Nedd8 conjugation led to a modest increase, rather than a decrease,
      in the overall level of most SCF complexes. We suggest that multiple mechanisms
      including FBP dissociation and turnover cooperate to maintain the cellular pool
      of SCF ubiquitin ligases.

PMID- 21169564
TI  - Index-ion triggered MS2 ion quantification: a novel proteomics approach for
      reproducible detection and quantification of targeted proteins in complex
      mixtures.
AB  - Biomedical research requires protein detection technology that is not only
      sensitive and quantitative, but that can reproducibly measure any set of proteins
      in a biological system in a high throughput manner. Here we report the
      development and application of a targeted proteomics platform termed index-ion
      triggered MS2 ion quantification (iMSTIQ) that allows reproducible and accurate
      peptide quantification in complex mixtures. The key feature of iMSTIQ is an
      approach called index-ion triggered analysis (ITA) that permits the reproducible
      acquisition of full MS2 spectra of targeted peptides independent of their ion
      intensities. Accurate quantification is achieved by comparing the relative
      intensities of multiple pairs of fragment ions derived from isobaric targeted
      peptides during MS2 analysis. Importantly, the method takes advantage of the
      favorable performance characteristics of the LTQ-Orbitrap, which include high
      mass accuracy, resolution, and throughput. As such it provides an attractive
      targeted proteomics tool to meet the demands of systems biology research and
      biomarker studies.

PMID- 21169566
TI  - Converging measures of workload capacity.
AB  - Does processing more than one stimulus concurrently impede or facilitate
      performance relative to processing just one stimulus? This fundamental question
      about workload capacity was surprisingly difficult to address empirically until
      Townsend and Nozawa (1995) developed a set of nonparametric analyses called
      systems factorial technology. We develop an alternative parametric approach based
      on the linear ballistic accumulator decision model (Brown & Heathcote, 2008),
      which uses the model's parameter estimates to measure processing capacity. We
      show that these two methods have complementary strengths, and that, in a data set
      where participants varied greatly in capacity, the two approaches provide
      converging evidence.

PMID- 21169567
TI  - The nature and position of processing determines why forgetting occurs in working
      memory tasks.
AB  - The effect of potentially distracting processing within working memory was
      examined by varying the nature and position of processing across conditions of a
      Brown-Peterson-like task. Separate groups of participants carried out verbal or
      visuospatial processing operations on identical stimuli, while retaining lists of
      to-be-remembered words. The number of words presented either before or after the
      processing interval was varied systematically. Results showed that although
      verbal processing was no more demanding than visuospatial processing, it led to
      greater forgetting. However, forgetting was confined to items presented prior to
      processing, and the difference in degree of forgetting shown by the two groups
      was maximal when four items occurred before processing. Temporal isolation
      effects were more marked in the verbal processing group. These findings indicate
      that individuals can keep active a limited number of items in primary memory
      during processing, unless processing blocks rehearsal, in which case retrieval
      occurs from secondary memory.

PMID- 21169568
TI  - Can associative information be strategically separated from item information in
      word-pair recognition?
AB  - Subjects learned word pairs either once or three times but were instructed to
      ignore the association of the two words in each pair and only to memorize the
      individual words at study and recognize them at test. The test word pairs
      included intact pairs, rearranged pairs made up of old words exchanged among the
      studied pairs, and new pairs consisting of one old and one new word. Subjects
      were instructed to respond yes to both intact and rearranged pairs and no to new
      pairs. Results showed that the rearranged test pairs, as compared with intact
      pairs, produced longer reaction times, lower discrimination (d'), and lower
      remember judgments. In addition, more learning either did not reduce or actually
      increased the pairing effect. These results are difficult to reconcile with the
      notion that associative information is retrieved in a slow, controlled, and
      effortful process but are consistent with the encoding specificity principle and
      the global activation theory of recognition.

PMID- 21169565
TI  - A proteomic and transcriptomic approach reveals new insight into beta
      methylthiolation of Escherichia coli ribosomal protein S12.
AB  - beta-methylthiolation is a novel post-translational modification mapping to a
      universally conserved Asp 88 of the bacterial ribosomal protein S12. This S12
      specific modification has been identified on orthologs from multiple bacterial
      species. The origin and functional significance was investigated with both a
      proteomic strategy to identify candidate S12 interactors and expression
      microarrays to search for phenotypes that result from targeted gene knockouts of
      select candidates. Utilizing an endogenous recombinant E. coli S12 protein with
      an affinity tag as bait, mass spectrometric analysis identified candidate S12
      binding partners including RimO (previously shown to be required for this post
      translational modification) and YcaO, a conserved protein of unknown function.
      Transcriptomic analysis of bacterial strains with deleted genes for RimO and YcaO
      identified an overlapping transcriptional phenotype suggesting that YcaO and RimO
      likely share a common function. As a follow up, quantitative mass spectrometry
      additionally indicated that both proteins dramatically impacted the modification
      status of S12. Collectively, these results indicate that the YcaO protein is
      involved in beta-methylthiolation of S12 and its absence impairs the ability of
      RimO to modify S12. Additionally, the proteomic data from this study provides
      direct evidence that the E. coli specific beta-methylthiolation likely occurs
      when S12 is assembled as part of a ribosomal subunit.

PMID- 21169569
TI  - Directed forgetting in young children: evidence for a production deficiency.
AB  - When people are cued to forget a previously studied list of items and to learn a
      new list instead, such cuing typically leads to forgetting of the first list and
      to memory enhancement of the second. In two experiments, we examined such
      listwise directed forgetting in children (and adults), using a forget cue that
      placed either high emphasis or low emphasis on the need to forget. In the low
      emphasis condition, (adult-like) List 1 forgetting was present in fourth graders,
      but not in first graders (and kindergartners); in contrast, in the high-emphasis
      condition, (adult-like) List 1 forgetting was present from first grade on. Only
      fourth graders showed (adult-like) List 2 enhancement, regardless of task
      instruction. The finding that first graders showed List 1 forgetting only in the
      high-emphasis condition points to a production deficiency in first graders'
      directed forgetting, suggesting that the children are capable of intentional
      forgetting but fail to do so spontaneously. The finding that first graders showed
      List 1 forgetting without List 2 enhancement suggests that the two directed
      forgetting effects are mediated by different processes with different
      developmental trajectories.

PMID- 21169570
TI  - Performing the unexplainable: implicit task performance reveals individually
      reliable sequence learning without explicit knowledge.
AB  - Memory-impaired patients express intact implicit perceptual-motor sequence
      learning, but it has been difficult to obtain a similarly clear dissociation in
      healthy participants. When explicit memory is intact, participants acquire some
      explicit knowledge and performance improvements from implicit learning may be
      subtle. Therefore, it is difficult to determine whether performance exceeds what
      could be expected on the basis of the concomitant explicit knowledge. Using a
      challenging new sequence-learning task, robust implicit learning was found in
      healthy participants with virtually no associated explicit knowledge.
      Participants trained on a repeating sequence that was selected randomly from a
      set of five. On a performance test of all five sequences, performance was best on
      the trained sequence, and two-thirds of the participants exhibited individually
      reliable improvement (by chi-square analysis). Participants could not reliably
      indicate which sequence had been trained by either recognition or recall. Only by
      expressing their knowledge via performance were participants able to indicate
      which sequence they had learned.

PMID- 21169571
TI  - The costs and benefits of providing feedback during learning.
AB  - It seems uncontroversial that providing feedback after a test, in the form of the
      correct answer, enhances learning. In real-world educational situations, however,
      the time available for learning is often constrained-and feedback takes time. We
      report an experiment in which total time for learning was fixed, thereby creating
      a trade-off between spending time receiving feedback and spending time on other
      learning activities. Our results suggest that providing feedback is not
      universally beneficial. Indeed, under some circumstances, taking time to provide
      feedback can have a negative net effect on learning. We also found that learners
      appear to have some insight about the costs of feedback; when they were allowed
      to control feedback, they often skipped unnecessary feedback in favor of
      additional retrieval attempts, and they benefited from doing so. These results
      underscore the importance of considering the costs and benefits of interventions
      designed to enhance learning.

PMID- 21169572
TI  - How inherently noisy is human sensory processing?
AB  - Like any physical information processing device, the human brain is inherently
      noisy: If a participant is presented with the same sensory stimulus multiple
      times and is asked to press one of two buttons in response to some property of
      the stimulus, the response may vary even though the stimulus did not. This
      response variability can be used to estimate the amount of so-called internal
      noise-that is, noise that is not present in the stimulus (such as random dynamic
      dots on the screen) but in the participant's brain. How large is this internally
      generated noise? We obtained >400 independent estimates on 40 participants for a
      range of protocols (yes/no, two-, four-, and eight-alternative forced choice),
      modalities (auditory and visual), attentional state, adaptation state, stimulus
      types (static, moving, stereoscopic), and other parameters (timing, size,
      contrast). Our final estimate at ~1.3 (units of external noise standard
      deviation) is generally somewhat larger than that previously inferred from
      smaller and less varied data sets. We discuss the impact of high levels of
      internal noise on a number of experimental and computational efforts aimed at
      understanding and characterizing human sensory processing.

PMID- 21169573
TI  - Temporal dynamics of generalization and representational distortion.
AB  - Individuals generalize differently depending on the extent of their past
      experiences and what they learn from them. For instance, the peak of
      generalization can shift from a familiar stimulus to novel ones when the familiar
      stimulus has been repeatedly discriminated from something similar. We examined
      how the amount of experience students had in discriminating complex sounds
      impacted their later generalization. As training increased, participants improved
      at distinguishing sounds, but their tendency to respond to certain novel sounds
      increased. With additional training, however, this shift dissipated. The results
      suggest that shifts in generalization may correspond to transitional states of
      perceptual learning and that learning-related changes in perceptual sensitivities
      involve more than just incremental increases in feature selectivity.

PMID- 21169574
TI  - Attentional capture under high perceptual load.
AB  - Attentional capture by abrupt onsets can be modulated by several factors,
      including the complexity, or perceptual load, of a scene. We have recently
      demonstrated that observers are less likely to be captured by abruptly appearing,
      task-irrelevant stimuli when they perform a search that is high, as opposed to
      low, in perceptual load (Cosman & Vecera, 2009), consistent with perceptual load
      theory. However, recent results indicate that onset frequency can influence
      stimulus-driven capture, with infrequent onsets capturing attention more often
      than did frequent onsets. Importantly, in our previous task, an abrupt onset was
      present on every trial, and consequently, attentional capture might have been
      affected by both onset frequency and perceptual load. In the present experiment,
      we examined whether onset frequency influences attentional capture under
      conditions of high perceptual load. When onsets were presented frequently, we
      replicated our earlier results; attentional capture by onsets was modulated under
      conditions of high perceptual load. Importantly, however, when onsets were
      presented infrequently, we observed robust capture effects. These results
      conflict with a strong form of load theory and, instead, suggest that exposure to
      the elements of a task (e.g., abrupt onsets) combines with high perceptual load
      to modulate attentional capture by task-irrelevant information.

PMID- 21169575
TI  - Monetary reward increases attentional effort in the flanker task.
AB  - An important question is whether monetary reward can increase attentional effort
      in order to improve performance. Up to now, evidence for a positive answer is
      weak. Therefore, in the present study, the flanker task was used to examine this
      question further. Participants had to respond sooner than a certain deadline in a
      flanker task. One group of participants received a performance-contingent
      monetary reward, whereas the other group earned a fixed amount of money. As a
      result, monetary reward significantly improved performance in comparison with the
      control group. The analysis of speed-accuracy trade-off functions revealed that
      monetary reward increased attentional effort, leading to an enhanced quality of
      stimulus coding. Little evidence was found that reward also improved selective
      spatial attention.

PMID- 21169576
TI  - Single-letter coloring and spatial cuing do not eliminate or reduce a semantic
      contribution to the Stroop effect.
AB  - The automaticity of semantic activation in the Stroop task is still the subject
      of considerable debate (Augustinova & Ferrand, 2007; Manwell, Roberts, & Besner,
      2004). The present experiments were designed to assess whether coloring and cuing
      a single letter (vs. all letters) in the Stroop task reliably eliminates
      semantically based Stroop interference or whether the elimination observed by
      Manwell et al. was due to insufficient statistical power. Experiment 1 was an
      exact replication of the experiment conducted by Manwell and colleagues and
      involved a large population. Experiment 2 replicated and extended Experiment 1 by
      controlling for initial fixation. In line with previous findings obtained by
      Augustinova and Ferrand, both experiments indicated that coloring and cuing a
      single letter failed to eliminate or even reduce the semantically based Stroop
      effect. Thus, these results add to the growing body of evidence suggesting that
      semantic activation in the Stroop task is automatic.

PMID- 21169577
TI  - Eye movements, the perceptual span, and reading speed.
AB  - The perceptual span or region of effective vision during eye fixations in reading
      was examined as a function of reading speed (fast readers were compared with slow
      readers), font characteristics (fixed width vs. proportional width), and
      intraword spacing (normal or reduced). The main findings were that fast readers
      (reading at about 330 wpm) had a larger perceptual span than did slow readers
      (reading about 200 wpm) and that the span was not affected by whether or not the
      text was fixed width or proportional width. In addition, there were interesting
      font and intraword spacing effects that have important implications for the
      optimal use of space in a line of text.

PMID- 21169578
TI  - Subitizing in congenitally blind adults.
AB  - We investigated the role of vision in tactile enumeration within and outside the
      subitizing range. Congenitally blind and sighted (blindfolded) participants were
      asked to enumerate quickly and accurately the number of fingers stimulated. Both
      groups of participants enumerated one to three fingers quickly and accurately but
      were much slower and less accurate with four to nine fingers. Within the
      subitizing range, blind participants performed no differently from both sighted
      (blindfolded) and sighted-seeing participants. Outside of the subitizing range,
      blind and sighted-seeing participants showed better performance than did sighted
      blindfolded participants, suggesting that lack of access to the predominant
      sensory modality does affect performance. Together, these findings further
      support the claim that subitizing is a general perceptual mechanism and
      demonstrate that vision is not necessary for the development of the subitizing
      mechanism.

PMID- 21169579
TI  - Spatial short-term memory assists in maintaining occluded objects.
AB  - We examined the role of spatial short-term memory (SSTM) in maintaining the
      hidden portions of occluded objects. We measured the degree of maintenance by
      asking participants to perform an object-based attention task on occluded objects
      while maintaining four locations in SSTM. SSTM did not interfere with object
      based selection generally. Maintenance of occluded portions of objects was
      prevented when four locations were held in SSTM and these locations did not
      overlap with the locations of occluded objects. Importantly, when the observers
      remembered locations that overlapped with the occluded regions of objects, the
      occluded objects were maintained behind the occluder. These results suggest that
      SSTM participates in maintaining the occluded sections of objects.

PMID- 21169580
TI  - Testing a postselectional account of across-dimension switch costs.
AB  - In visual search for a pop-out target, responses are faster when the target
      dimension from the previous trial is repeated than when it changes. Currently, it
      is unclear whether these across-dimension switch costs originate from processes
      that guide attention to the target or from later processes (e.g., target
      identification or response selection). The present study tested two critical
      predictions of a response-selection account of across-dimension switch costs
      namely, (1) that switch costs should occur even when visual attention is guided
      by a completely different feature and (2) that changing the target dimension
      should affect the speed of responding, but not the speed of eye movements to the
      target. The results supported both predictions, indicating that changes of the
      target dimension do not affect early processes that guide attention to the target
      but, rather, affect later processes, which commence after the target has been
      selected.

PMID- 21169581
TI  - Atypical categorization in children with high-functioning autism spectrum
      disorder.
AB  - Children with autism spectrum disorder process many perceptual and social events
      differently from typically developing children, suggesting that they may also
      form and recognize categories differently. We used a dot pattern categorization
      task and prototype comparison modeling to compare categorical processing in
      children with high-functioning autism spectrum disorder and matched typical
      controls. We were interested in whether there were differences in how children
      with autism use average similarity information about a category to make
      decisions. During testing, the group with autism spectrum disorder endorsed
      prototypes less and was seemingly less sensitive to differences between to-be
      categorized items and the prototype. The findings suggest that individuals with
      high-functioning autism spectrum disorder are less likely to use overall average
      similarity when forming categories or making categorical decisions. Such
      differences in category formation and use may negatively impact processing of
      socially relevant information, such as facial expressions. A supplemental
      appendix for this article may be downloaded from http://pbr.psychonomic
      journals.org/content/supplemental.

PMID- 21169582
TI  - Speeded induction under uncertainty: the influence of multiple categories and
      feature conjunctions.
AB  - When people are uncertain about the category membership of an item (e.g., Is it a
      dog or a dingo?), research shows that they tend to rely only on the dominant or
      most likely category when making inductions (e.g., How likely is it to befriend
      me?). An exception has been reported using speeded induction judgments where
      participants appeared to use information from multiple categories to make
      inductions (Verde, Murphy, & Ross, 2005). In two speeded induction studies, we
      found that participants tended to rely on the frequency with which features co
      occurred when making feature predictions, independently of category membership.
      This pattern held whether categories were considered implicitly (Experiment 1) or
      explicitly (Experiment 2) prior to feature induction. The results converge with
      other recent work suggesting that people often rely on feature conjunction
      information, rather than category boundaries, when making inductions under
      uncertainty.

PMID- 21169583
TI  - Morphemic ambiguity resolution in Chinese: activation of the subordinate meaning
      with a prior dominant-biased context.
AB  - In the present study, we examined how morphemic ambiguity is resolved using the
      visual-world paradigm. Participants were presented with Chinese bimorphemic words
      containing an ambiguous morpheme (analogous to the suffix -er in teacher and
      taller) and performed a visual search task. Their eye-movement patterns during
      target detection showed that (1) without a prior context, the dominant meaning of
      an ambiguous morpheme was more available than the subordinate one; (2) with a
      dominant-biased prior context, the subordinate meaning was still activated; and
      (3) a subordinate-biased prior context could inhibit the dominant interpretation.
      Therefore, both the frequency of the intended meaning and the prior contextual
      biases play a role in morphemic ambiguity resolution. The results are discussed
      with reference to models of ambiguity resolution and recent proposals of the
      graded nature of morphological effects.

PMID- 21169584
TI  - Processing unrelated language can change what you see.
AB  - When we hear a story, do we naturally imagine the visual scene being described?
      Do the representations derived in the course of normal language comprehension
      interact with visual perception broadly? For example, might understanding
      language change how we interpret visual scenes, even when the visual scenes are
      unrelated to the linguistic content? In our study, people interpreted an
      ambiguous image after they had (1) seen real visual motion either upward or
      downward (Experiment 1), (2) read a story describing physical motion (Experiment
      2), or (3) read a story describing abstract motion (Experiment 3). The ambiguous
      figure could have been seen as a bird flying upward or a different bird flying
      downward, and the participants were simply asked to click on or draw a worm in
      the bird's beak. People's interpretations of the ambiguous figure were affected
      by viewing real motion and by reading literal stories describing physical motion,
      but not by the abstract motion stories. These findings suggest that processing
      linguistic descriptions of physical (but not abstract) motion can bias perceptual
      processing in a broad sense; in this case, reading about physical motion changed
      people's interpretation of an unrelated ambiguous image.

PMID- 21169585
TI  - Dissociating between cardinal and ordinal and between the value and size
      magnitudes of coins.
AB  - In mathematics, the ordinal (relative) magnitude of a numerical object conveys a
      separate meaning from its cardinal (absolute) magnitude, whereas its physical
      size bears no inherent relationship to its magnitude. In numerical cognition, the
      ordinal-cardinal distinction has been scarcely addressed, whereas the size
      magnitude distinction has been studied extensively, with the surprising
      demonstration of an interaction between semantic magnitude and physical size
      (Besner & Coltheart, 1979). The present work used coins to study the intricate
      relations between these meanings. In two experiments, Israeli observers
      (Experiment 1) and American observers (Experiment 2) performed numerical and
      physical comparative judgments of coins. Consensual markers of magnitude
      activation (e.g., the size congruity effect and the distance effect) were
      obtained. The results of the two experiments converged on the same conclusions.
      Comparisons of value were governed by ordinal magnitude. Magnitude interfered
      with comparisons of size, but size did not affect value. The results provided a
      set of clear dissociations between cardinal and ordinal magnitude and between
      value and size of coins. They highlight the important role played by ordinal
      information in magnitude processing.

PMID- 21169586
TI  - Unilateral muscle contractions enhance creative thinking.
AB  - Following the notion of relative importance of the right hemisphere (RH) in
      creative thinking, we explored the possibility of enhancing creative problem
      solving by artificially activating the RH ahead of time using unilateral hand
      contractions. Participants attempted to complete the Remote Associates Test after
      squeezing a ball with either their left or right hand. As predicted, participants
      who contracted their left hand (thus activating the RH) achieved higher scores
      than those who used their right hand and those who did not contract either hand.
      Our findings indicate that tilting the hemispheric balance toward the processing
      mode of one hemisphere by motor activation can greatly influence the outcome of
      thought processes. Regardless of the specific mechanism involved, this technique
      has the potential for acting as a therapeutic or remedial manipulation and could
      have wide applications in aiding individuals with language impairments or other
      disorders that are believed to be related to hemispheric imbalances.

PMID- 21169587
TI  - Walking through doorways causes forgetting: environmental integration.
AB  - Memory for objects declines when people move from one location to another (the
      location updating effect). However, it is unclear whether this is attributable to
      event model updating or to task demands. The focus here was on the degree of
      integration for probed-for information with the experienced environment. In prior
      research, the probes were verbal labels of visual objects. Experiment 1 assessed
      whether this was a consequence of an item-probe mismatch, as with transfer
      appropriate processing. Visual probes were used to better coordinate what was
      seen with the nature of the memory probe. In Experiment 2, people received
      additional word pairs to remember, which were less well integrated with the
      environment, to assess whether the probed-for information needed to be well
      integrated. The results showed location updating effects in both cases. These
      data are consistent with an event cognition view that mental updating of a
      dynamic event disrupts memory.

PMID- 21169588
TI  - Nested prospectivity in perception: perceived maximum reaching height reflects
      anticipated changes in reaching ability.
AB  - Perception of possibilities for behavior is a necessarily prospective (i.e.,
      forward-looking) act. Such prospectivity is highlighted by the fact that, in
      general, behaviors are nested within behaviors over a number of spatial and
      temporal scales. Participants reported their maximum vertical reaching height
      when they expected to walk across the room and (1) reach for an object while
      standing on the floor, (2) step up on a step stool and then reach for the object,
      and (3) pick up a plastic rod and use it to reach for the object. The results
      show that perception of maximum reaching height was action scaled both when
      participants expected to perform a nested behavior that would change their action
      capabilities and when they expected to perform a nested behavior that would not
      do so. Moreover, the results suggest that nested behaviors that change reaching
      ability in functionally equivalent ways may bring about functionally equivalent
      changes in perception of maximum reaching height.

PMID- 21169589
TI  - Feeling socially powerless makes you more prone to bumping into things on the
      right and induces leftward line bisection error.
AB  - Social power affects the manner in which people view themselves and act toward
      others, a finding that has attracted broad interest from the social and political
      sciences. However, there has been little interest from those within cognitive
      neuroscience. Here, we demonstrate that the effects of power extend beyond social
      interaction and invoke elementary spatial biases in behavior consistent with
      preferential hemispheric activation. In particular, participants who felt
      relatively powerless, compared with those who felt more powerful, were more
      likely to bisect horizontal lines to the left of center, and bump into the right
      hand (as opposed to the left-hand) side when walking through a narrow passage.
      These results suggest that power induces hemispheric differences in visuomotor
      behavior, indicating that this ubiquitous phenomenon affects not only how we
      interact with one another, but also how we interact with the physical world.

PMID- 21169590
TI  - Temporal control of internal states in pigeons.
AB  - To understand how animals serially organize complex competing behaviors, we
      tested pigeons in a sequential task-switching procedure. Daily sessions involved
      two conditional discrimination tasks that were presented in sequence. In
      Experiment 1, the first half of a session employed a matching-to-sample task, and
      the second half tested an oddity-from-sample task. Because the same colors were
      used for both tasks, these tasks could be solved only by employing a modulating
      sequential cue. The results of the first experiment revealed that the pigeons
      could learn this task-switching procedure and that an internal clock was the
      critical modulator between the tasks. In Experiment 2, we tested a three
      alternative choice task. By examining the pattern of errors among choices, the
      results of this experiment revealed that pigeons learned and used different
      representations of the choice rules for each half of the experiment. This
      modulation of the pigeons' internal states by time has implications for how
      animals organize their behavior in different settings and holds clues as to the
      evolution of the serial organization of behavior.

PMID- 21169591
TI  - Reconsidering "evidence" for fast-and-frugal heuristics.
AB  - In several recent reviews, authors have argued for the pervasive use of fast-and
      frugal heuristics in human judgment. They have provided an overview of heuristics
      and have reiterated findings corroborating that such heuristics can be very valid
      strategies leading to high accuracy. They also have reviewed previous work that
      implies that simple heuristics are actually used by decision makers.
      Unfortunately, concerning the latter point, these reviews appear to be somewhat
      incomplete. More important, previous conclusions have been derived from
      investigations that bear some noteworthy methodological limitations. I
      demonstrate these by proposing a new heuristic and provide some novel critical
      findings. Also, I review some of the relevant literature often not-or only
      partially-considered. Overall, although some fast-and-frugal heuristics indeed
      seem to predict behavior at times, there is little to no evidence for others.
      More generally, the empirical evidence available does not warrant the conclusion
      that heuristics are pervasively used.

PMID- 21169593
TI  - Cutaneous sarcoids in captive African lions associated with feline sarcoid
      associated papillomavirus infection.
AB  - Solitary and multiple cutaneous and mucocutaneous masses were identified in 5 of
      24 captive African lions (Panthera leo) over a 6-month-period. All masses were
      surgically excised, and all were histologically similar to equine and feline
      sarcoids. DNA was extracted from formalin-fixed, paraffin-embedded tissue.
      Polymerase chain reaction amplified DNA sequences that had been previously
      detected in feline sarcoids and clinically normal bovine skin. All lions had been
      fed a diet that included bovine carcasses that had not been skinned. Since the
      cessation of feeding bovine carcasses with cutaneous lesions, no additional skin
      lesions have been observed within any of the lions. Herein is described the
      clinical, gross, and histopathological findings of sarcoids in 5 captive lions.
      As the causative papillomavirus most likely has a bovine definitive host, it is
      hypothesized that the lions were exposed to the virus by feeding on bovine
      carcasses with skin still attached.

PMID- 21169594
TI  - Special issue on Pacific health.

PMID- 21169595
TI  - Health of Pacific Islanders: achievements and challenges.

PMID- 21169596
TI  - Mortality trends and the epidemiological transition in Nauru.
AB  - This article aims to examine the epidemiological transition in Nauru through
      analysis of available mortality data. Mortality data from death certificates and
      published material were used to construct life tables and calculate age
      standardized mortality rates (from 1960) with 95% confidence intervals.
      Proportional mortality was calculated from 1947. Female life expectancy (LE)
      varied from 57 to 61 years with no significant trend. Age-standardized mortality
      for males (15-64 years) doubled from 1960-1970 to 1976-1981 and then decreased to
      1986-1992, with LE fluctuating since then from 49 to 54 years. Proportional
      mortality from cardiovascular disease and diabetes increased substantially,
      reaching more than 30%. Nauru demonstrates a very long period of stagnation in
      life expectancy in both males and females as a consequence of the epidemiological
      transition, with major chronic disease mortality in adults showing no sustained
      downward trends over 40 years. Potential overinterpretation of trends from
      previous data due to lack of confidence intervals was highlighted.

PMID- 21169597
TI  - Tongan adolescents' eating patterns: opportunities for intervention.
AB  - The purpose of this mixed methods study was to examine the sources of food and
      dietary patterns of Tongan adolescents (n = 2084) and their perceptions of
      sociocultural influences. The study incorporated anthropometric measurements, a
      behavioral survey, and qualitative interviews. More adolescent Tongan females
      (82.5%) than males (74.3%) reported sourcing morning tea and/or lunch (females
      81.9%, males 72.6%) from school canteens or nearby food outlets. More females
      than males reported consuming obesity-promoting foods such as packaged snack
      foods (females 38.2%, males 21.3%), chocolates (females 24.7%, males 15.0%), and
      soft drinks (females 55.3%, males 50.4%). Food purchased for consumption at
      schools was predominantly energy dense and nutrient poor. Ensuring that students
      have access to foods of high nutritional quality sourced from school or home, and
      restricting access to local food outlets that supply unhealthy products would
      improve the nutrition status of adolescents in Tonga. Furthermore, it is
      important that obesity prevention interventions are informed by culture-specific
      influences to optimize uptake of healthy diets.

PMID- 21169598
TI  - Body mass index among Melanesian and Indian Fijians aged >= 40 years living in
      Fiji.
AB  - To determine the distribution and sociodemographic associations of body mass
      index (BMI; kg/m(2)) among Melanesian and Indian Fijians aged >=40 years living
      in Fiji, a population-based cross-sectional survey with multistage random
      sampling was conducted in 2009. Melanesians were more likely to have BMI >=25
      (odds ratio [OR] = 4.73; 95% confidence interval [CI] = 3.57-6.28; P < .001) and
      BMI >=30 (OR = 3.84; 95% CI = 2.94-5.03; P < .001). Among Melanesians, gender and
      educational attainment were predictive of BMI >=25 on multivariate analysis.
      Women were more likely to be overweight (OR = 2.03; 95% CI = 1.34-3.06) or obese
      (OR = 1.92; 95% CI = 1.43-2.59). Among Indians, gender and age were predictive of
      BMI >=25. Again, women were more likely to be overweight (OR = 2.51; 95% CI =
      1.69-3.73) or obese (OR = 3.71; 95% CI = 2.19-6.29). Gender-age-domicile
      adjusted, and extrapolating across Fiji, 0.3%, 84.5%, and 51.7% of Melanesians
      aged >=40 years had BMI <18.5, >=25, and >=30, respectively. Among Indians, these
      values were 5.8%, 54.2%, and 21.2%, respectively.

PMID- 21169599
TI  - Psychosocial profiles of adolescent nonsmokers in the Pacific.
AB  - Studies examining adolescent smoking have focused on at-risk individuals, while
      overlooking the psychosocial profiles of those adolescents who have managed to
      remain nonsmokers. Accumulating evidence suggests that positive emotions such as
      happiness may be associated with the adoption of healthy practices, but limited
      evidence has emerged from developing countries. This study examined the
      association between non-smoking and positive emotions and psychosocial correlates
      in 3 large population samples of Pacific youths (N = 5659) living in Tonga,
      Vanuatu, and Pohnpei in the Federated States of Micronesia. Across all 3 samples,
      being confident was significantly associated with nonsmoking and being happy
      (Tonga, odds ratio [OR] = 1.39, 95% confidence interval [CI] = 1.12-1.73;
      Vanuatu, OR = 1.29, 95% CI = 1.02-1.63; Pohnpei, OR = 2.34, 95% CI = 1.60-3.34).
      Some cross-country differences in relationships were found in the associations
      between societal factors (ie, perceived connections with school, teachers, and
      peers, and perceived community importance and involvement) and nonsmoking and
      happiness. Findings have implications for developing innovative strategies aimed
      at preventing smoking uptake and suggest the need for focusing on identifying the
      determinants of nonsmoking and measuring positive emotions.

PMID- 21169600
TI  - Tobacco promotion in the Pacific: the current state of tobacco promotion bans and
      options for accelerating progress.
AB  - Tobacco consumption is a major contributor to the burden of chronic
      noncommunicable disease within the Pacific region. Low and lower-middle income
      countries are acutely vulnerable to exploitation by the tobacco industry as they
      often lack the resources and capacity to implement protective tobacco control
      policies. The Framework Convention on Tobacco Control, which has been signed by
      14 Pacific Island Countries and Territories, was introduced in 2004 to guide the
      priorities for tobacco control policy implementation. Legislation, tobacco
      industry documents, and peer-reviewed journals were evaluated to assess the
      current status of tobacco advertising bans of the 8 low and lower-middle income
      countries within the Pacific region. RESULTS: identified that of the 8 Pacific
      countries reviewed, 3 had comprehensive tobacco advertising bans that prohibit
      tobacco advertisements in 5 to 7 forms of media, and the remaining 5 countries
      have weak tobacco advertising bans that provide no protection for youth against
      tobacco advertising. This research reveals the need for resources to support the
      introduction of effective policies around tobacco advertising in the low and
      lower-middle income countries within the Pacific region.

PMID- 21169601
TI  - Ensuring economic, health, and social well-being for Papua New Guinea through
      trade.
AB  - The impacts of trade liberalization and open markets on global, regional, and
      local economies are a key consideration for those involved in government,
      business, and financial sectors. However, their impacts on health and social well
      being of populations are not well-evidenced acknowledged within the health
      sector, let alone the impact on developing countries. As free trade becomes an
      inevitable outcome for many developing nations, the full implications of trade on
      economies, environments, and population health needs to be better articulated in
      order to ensure fully informed trade negotiations that support equitable
      outcomes. This article takes a broad look at the key issues for Papua New Guinea
      (PNG) in trade and how these translate to discrepancies in economic, health, and
      social benefits for its population. Despite its active trading and high GDP, only
      10% of the population experience better economic and social outcomes. The bulk of
      PNG's population lives in poverty, challenged by geographical, cultural, and
      political barriers to better income, education, and health. Progress needs to be
      made to minimize these barriers and to allow more of PNG's population to
      experience the economic benefits generated through trade activities. A balance
      needs to be maintained between the desire of developed countries to broaden their
      markets, and the efforts of developing countries to promote and protect the
      health and well-being of their populations through increasing participation in
      global markets. PACER Plus presents an opportunity for pursuing alternative
      models of trade agreements that support and develop Pacific health.

PMID- 21169602
TI  - The epidemiology of tuberculosis in Pacific Island countries and territories:
      2000-2007.
AB  - This is a descriptive study of routinely collected tuberculosis (TB) surveillance
      data from 19 Pacific Island countries and territories. The objectives of the
      study are to describe (a) the epidemiology of TB during the period 2000-2007
      (with a focus on 2007), (b) progress against World Health Organization (WHO)
      targets, and (c) how TB control can be enhanced in the region. In 2007, there
      were 1544 cases of TB notified in the Pacific (excluding Papua New Guinea). The
      case notification rate was 52 per 100 000 population. The case detection rate for
      sputum smear positive cases in 2007 was 66%, slightly below the WHO target of
      70%. The treatment success rate for new sputum smear positive cases in 2006 was
      89%, above the WHO target of 85%. It is likely that the regional prevalence and
      mortality targets will be narrowly missed in 2010. There has been good progress
      in TB control in the Pacific region, but intensified efforts are needed to
      further reduce the burden of TB.

PMID- 21169603
TI  - Strengthening health research capacity from within Samoa.
AB  - This article reflects on the challenges of strengthening health research capacity
      from within Samoa. It examines the status of health research and related
      curricula in Samoa and discusses the outcomes of a new postgraduate applied
      social and health research methods course taught in Samoa for the first time from
      5 January to 12 February 2010 by the Department of Preventive and Social
      Medicine, University of Otago in collaboration with the Centre for Samoan
      Studies, National University of Samoa. The article argues that collaborative
      health research courses such as this methods paper can fill a curriculum gap in
      New Zealand and Samoa and contribute directly toward strengthening Samoa health
      research capacity in ways that benefit both Samoa and New Zealand. This
      initiative can be a flagship for strategies operating from within Samoa that can
      build real win-win type partnerships. These can be ably led by Samoans for the
      ultimate development of an affordable and sustainable quality health and
      education infrastructure for Samoa.

PMID- 21169604
TI  - Challenges of noncommunicable diseases in the Pacific Islands: the need for
      evidence and data.

PMID- 21169605
TI  - Prevalence of injecting drug use among youth in the Pacific Island countries and
      territories: what is the evidence?

PMID- 21169606
TI  - The role of pacemaker in hypersensitive carotid sinus syndrome.
AB  - AIMS: About 15% of patients with the hypersensitive carotid sinus syndrome (CSS)
      have no clinical improvement after permanent pacemaker implantation. We aimed to
      assess the outcome of patients with CSS treated with pacemaker and to determine
      predictors of symptoms' recurrence. METHODS AND RESULTS: A retrospective analysis
      of 138 patients in whom pacemaker was implanted for CSS was carried out from
      February 1990 to October 2008. Data were collected from clinical records. Mean
      age was 69 +/- 10.7 years and 104 patients (75.4%) were men. Mean follow-up
      period was 4.9 +/- 4.4 years. Twenty-one (15.2%) patients presented mixed CSS and
      117 (84.8%) cardioinhibitory CSS. The head-up tilt test (HUTT) was performed in
      93 patients (67.4%). After pacemaker implantation, 115 (83.3%) patients had no
      further symptoms, 8 (5.8%) presented minor symptoms and in 15 (10.9%), the
      symptoms remained unchanged. Among patients with symptoms' recurrence, 8 (38.1%)
      had mixed CSS and 15 (12.8%) cardioinhibitory CSS. Mixed CSS was the only
      independent predictor of symptoms' recurrence in total population {hazard ratio
      (HR) 2.84 [95% confidence intervals (CI) 1.20-6.71]; P = 0.017} and in patients
      who performed HUTT [HR 1.84 (95% CI 1.01-3.35); P = 0.045]. Although the HUTT
      result was not related to symptoms' recurrence, patients with mixed CSS were more
      likely to present a vasodepressor response (61.9 vs. 19.4%; P < 0.001) and a
      reproduction of spontaneous symptoms (28.6 vs. 2.8%; P = 0,001) on HUTT.
      CONCLUSIONS: Permanent pacemaker is an effective treatment for CSS. However, the
      recurrence of symptoms was two- to three-fold more frequent in patients with
      mixed CSS, probably due to the persistence of vasodepressor component.

PMID- 21169607
TI  - A golden opportunity to celebrate the 50th anniversary of the Society of
      Toxicology.

PMID- 21169608
TI  - Arbuscular mycorrhizal fungi alter plant allometry and biomass-density
      relationships.
AB  - BACKGROUND AND AIMS: Plant biomass-density relationships during self-thinning are
      determined mainly by allometry. Both allometry and biomass-density relationship
      have been shown to vary with abiotic conditions, but the effects of biotic
      interactions have not been investigated. Arbuscular mycorrhizal fungi (AMF) can
      promote plant growth and affect plant form. Here experiments were carried out to
      test whether AMF affect plant allometry and the self-thinning trajectory.
      METHODS: Two experiments were conducted on Medicago sativa L., a leguminous
      species known to be highly dependent on mycorrhiza. Two mycorrhizal levels were
      obtained by applying benomyl (low AMF) or not (high AMF). Experiment 1
      investigated the effects of AMF on plant growth in the absence of competition.
      Experiment 2 was a factorial design with two mycorrhizal levels and two plant
      densities (6000 and 17 500 seeds m(-2)). Shoot biomass, root biomass and canopy
      radius were measured 30, 60, 90 and 120 d after sowing. The allometric
      relationships among these aspects of size were estimated by standardized major
      axis regression on log-transformed data. KEY RESULTS: Shoot biomass in the
      absence of competition was lower under low AMF treatment. In self-thinning
      populations, the slope of the log (mean shoot biomass) vs. log density
      relationship was significantly steeper for the high AMF treatment (slope = 
      1.480) than for the low AMF treatment (-1.133). The canopy radius-biomass
      allometric exponents were not significantly affected by AMF level, but the root
      shoot allometric exponent was higher in the low AMF treatment. With a high level
      of AMF, the biomass-density exponent can be predicted from the above-ground
      allometric model of self-thinning, while this was not the case when AMF were
      reduced by fungicide. CONCLUSIONS: AMF affected the importance of below-ground
      relative to above-ground interactions and changed root vs. shoot allocation. This
      changed allometric allocation of biomass and altered the self-thinning
      trajectory.

PMID- 21169609
TI  - Additional femoral catheter in combination with popliteal catheter for analgesia
      after major ankle surgery.
AB  - BACKGROUND: The contribution of the saphenous nerve in pain after major ankle
      surgery is unknown. The aim of this study was to evaluate its contribution in
      this context. METHODS: Fifty patients were included in this prospective,
      randomized, controlled study. In all patients [Group P (popliteal) and Group F
      (popliteal+femoral)], a popliteal catheter was placed before operation and
      ropivacaine 0.5% (30 ml) administered via this catheter; major ankle surgery was
      then performed under spinal anaesthesia. In Group PF patients, an additional
      femoral catheter was sited before operation and ropivacaine 0.5% (10 ml)
      administered. Six hours after spinal anaesthesia (defined as T(0)), a continuous
      infusion of ropivacaine 0.3% (14 ml h(-1)) was started through the popliteal
      catheter until T(24). Then, the concentration was reduced to 0.2% until T(48).
      Patients in Group PF received continuous ropivacaine 0.2% (5 ml h(-1)) through
      the femoral catheter from T(0) to T(48). I.V. morphine patient-controlled
      analgesia was used as a rescue analgesia. Pain at rest, pain with movement,
      adverse effects, and i.v. morphine consumption were assessed. Pain at rest and on
      movement was evaluated 6 months after operation. RESULTS: Pain at rest was
      comparable in the two groups. In Group PF, patients had significantly reduced
      pain during movement in the postoperative period (P=0.01) and 6 months after
      operation (P=0.03). Morphine consumption was significantly reduced in Group PF at
      T(0)-T(24) and T(24)-T(48) (P=0.01). Adverse effects were comparable in both
      groups. CONCLUSIONS: The addition of continuous femoral catheter infusion of
      ropivacaine to a continuous popliteal catheter infusion improved postoperative
      analgesia during movement after major ankle surgery. This effect was still
      present 6 months after surgery.

PMID- 21169610
TI  - Antinociceptive effect of intrathecal ginsenosides through alpha-2 adrenoceptors
      in the formalin test of rats.
AB  - BACKGROUND: We defined the nature of the pharmacological interaction after
      intrathecal co-administration of ginsenosides with clonidine, and clarified the
      contribution of the alpha-2 adrenoceptors on the effect of ginsenosides. METHODS:
      Pain was evoked by injection of a formalin solution (5%, 50 MUl) into the hindpaw
      of male Sprague-Dawley rats. Isobolographic analysis was performed to
      characterize the drug interaction between ginsenosides and clonidine. The
      antagonism of ginsenosides-mediated antinociception was determined with alpha-2A
      (BRL 44408), alpha-2B (ARC 239), and alpha-2C (JP 1302) adrenoceptor antagonists.
      The expression of alpha-2 adrenoceptor subtypes was examined by reverse
      transcriptase-polymerase chain reaction. RESULTS: Intrathecal ginsenosides (n=29)
      and clonidine (n=31) displayed an antinociceptive effect. The ED(50) values (95%
      confidence intervals) of ginsenosides and clonidine for phases 1 and 2 were 109.5
      (63-190.3) and 110.9 (57.1-215.5), and 11.8 (3.7-37.1) and 4.9 (3.1-6.7) MUg,
      respectively. With an isobolographic study (n=48), the ED(50) values (95%
      confidence intervals) of ginsenosides in the combination of ginsenosides and
      clonidine for phases 1 and 2 were 58.2 (38.9-87.3) and 57.2 (46.5-70.3) MUg,
      respectively. Intrathecal BRL 44408 (n=6), ARC 239 (n=5), and JP 1302 (n=5)
      reversed the antinociception of ginsenosides in both phases (P<0.01, <0.001). The
      injection of formalin increased the expression of alpha-2C adrenoceptor in the
      spinal cord (P<0.05). CONCLUSIONS: Intrathecal ginsenosides additively interacted
      with clonidine in the formalin test. Furthermore, alpha-2A, -B, and -C
      adrenoceptors contributed to the antinociception of intrathecal ginsenosides.

PMID- 21169611
TI  - Androgen receptor polyglutamine length does not influence serum levels of
      adipocytokines in alcoholism: a preliminary retrospective analysis.
AB  - AIMS: In recent years, various studies were able to show a link between serum
      levels of appetite-regulating peptides and alcoholism. The adipocytokines,
      adiponectin and resistin seem to be altered during withdrawal. We recently showed
      that a trinucleotide polymorphism within the coding region of the androgen
      receptor (AR) is linked to craving in alcohol withdrawal, an effect that was
      mostly mediated by leptin. The aim of the present preliminary retrospective study
      was to further elucidate whether adiponectin and resistin serum levels are
      regulated by this AR polymorphism as well. METHODS: We included 50 male in
      patients who were admitted for detoxification treatment. Each had a diagnosis of
      alcohol dependence (DSM-IV). RESULTS: Our analyses revealed that adiponectin
      serum levels significantly decreased, whereas resistin levels slightly increased
      between the day of admission and Day 7. Beyond that, we were not able to
      demonstrate significant associations between the investigated CAG polymorphism of
      the AR and adiponectin, resistin or leptin-corrected adipocytokines, either on
      the day of admission or on Day 7. Moreover, the polymorphism did not influence
      the time response of adiponectin and resistin during withdrawal. CONCLUSIONS:
      Genetic determinants of the AR influence alcohol withdrawal. Anyway, this
      preliminary retrospective analysis does not support the hypothesis that the
      investigated AR polymorphism has a major modifying effect on adiponectin or
      resistin serum levels in patients with alcoholism.

PMID- 21169612
TI  - The stigma of alcohol dependence compared with other mental disorders: a review
      of population studies.
AB  - AIMS: Stigma is likely to aggravate the severe medical and social consequences of
      alcohol dependence. We aim to explore the characteristics of the alcohol
      dependence stigma by comparing it with the stigma of other conditions. METHODS:
      On the basis of a systematic literature search, we identified 17 representative
      population studies published before July 2010 that examine aspects of the stigma
      of alcoholism and simultaneously of other mental, medical or social conditions.
      Seven surveys were located in Europe, five in North America, three in New Zealand
      and one each in Brazil and Ethiopia, respectively. RESULTS: Compared with people
      suffering from other, substance-unrelated mental disorders, alcohol-dependent
      persons are less frequently regarded as mentally ill, are held much more
      responsible for their condition, provoke more social rejection and more negative
      emotions, and they are at particular risk for structural discrimination. Only
      with regard to being a danger, they are perceived to be at a similarly negative
      level to that of people suffering from schizophrenia. CONCLUSION: Alcoholism is a
      particularly severely stigmatized mental disorder. Cultural differences are
      likely, but under-researched. We discuss possible reasons for the differences
      between the stigma of alcoholism and of other mental diseases and the
      consequences for targeted anti-stigma initiatives.

PMID- 21169613
TI  - Familial ventricular aneurysms and septal defects map to chromosome 10p15.
AB  - AIMS: Although ventricular septal defects (VSD) are the most common congenital
      heart lesion, familial clustering has been described only in rare instances. The
      aim of this study was to identify genetic factors and chromosomal regions
      contributing to VSD. METHODS AND RESULTS: A unique, large kindred segregating
      various forms of septal pathologies-including VSD, ventricular septal aneurysms,
      and atrial septal defects (ASD)-was ascertained and characterized clinically and
      genetically. Eighteen family members in three generations could be studied, out
      of whom 10 are affected (2 ASD, 3 septal aneurysm, 4 VSD, and 1 tetralogy of
      Fallot). Parametric multipoint LOD scores reach significance on chromosome
      10p15.3-10p15.2 (max. 3.29). The LOD score support interval is in a gene-poor
      region where deletions have been reported to associate with septal defects, but
      that is distinct from the DiGeorge syndrome 2 region on 10p. Multiple linkage
      analysis scenarios suggest that tetralogy of Fallot is a phenocopy and
      genetically distinct from the autosomal dominant form of septal pathologies
      observed in this family. CONCLUSION: This study maps a rare familial form of
      VSD/septal aneurysms to chromosome 10p15 and extends the spectrum of the genetic
      heterogeneity of septal pathologies. Fine mapping, haplotype construction, and
      resequencing will provide a unique opportunity to study the pathogenesis of
      septal defects and shed light on molecular mechanisms of septal development.

PMID- 21169614
TI  - Additional impact of morning haemostatic risk factors and morning blood pressure
      surge on stroke risk in older Japanese hypertensive patients.
AB  - AIMS: Stroke events occur most frequently in the morning hours. Impaired
      haemostatic activity and morning blood pressure (BP) surge, defined as the
      morning BP increase from sleep, have individually been associated with stroke
      risk in general or hypertensive populations. However, their combined impact on
      the risk of a stroke remains unknown. METHODS AND RESULTS: A total of 514
      hypertensive patients aged > 50 years (mean 72.3 years; 37% men) underwent 24 h
      BP monitoring, measurement of haemostatic risk factors [plasma fibrinogen,
      plasminogen activator inhibitor-1 (PAI-1), and prothrombin fragment 1+2(F1+2)],
      and brain MRI at baseline. The incidence of stroke was prospectively ascertained.
      During an average of 41 months (1751 person-years), there were 43 stroke events
      (ischaemic, 30; haemorrhagic, 5; undefined, 8). On multivariable analysis
      adjusted for confounding factors, the hazard ratio [HR (95% confidence interval
      (CI)] for stroke in the highest vs. lower quartiles of PAI-1 was 2.5 (1.3-4.6),
      that for F1+2 was 2.6 (1.4-5.0), and that for the morning BP surge was 1.2 (1.1
      1.4; all P< 0.01). In particular, the ratio was substantially higher in cases
      with the highest quartile of both PAI-1 and F1+2 levels compared with those with
      the lower quartiles of both parameters (HR: 8.2; 95% CI: 3.7-18.2; P< 0.001).
      Among the patients with the highest quartile of the morning BP surge (n= 128),
      the multivariable HR (95% CI) for the highest vs. lower quartiles of PAI-1 was
      3.4 (1.3-9.1) and that for F1+2 was 3.3 (1.3-8.7) (both P< 0.05). CONCLUSION:
      High levels of plasma PAI-1 and F1+2, as well as an excessive morning BP surge,
      are independently and additively associated with an increased risk of stroke in
      older hypertensive patients.

PMID- 21169615
TI  - Troponin elevation in coronary vs. non-coronary disease.
AB  - Acute myocardial infarction is defined as myocardial cell death due to prolonged
      myocardial ischaemia. Cardiac troponins (cTn) are the most sensitive and specific
      biochemical markers of myocardial injury and with the new high-sensitivity
      troponin methods very minor damages on the heart muscle can be detected. However,
      elevated cTn levels indicate cardiac injury, but do not define the cause of the
      injury. Thus, cTn elevations are common in many disease states and do not
      necessarily indicate the presence of a thrombotic acute coronary syndrome (ACS).
      In the clinical work it may be difficult to interpret dynamic changes of troponin
      in conditions such as stroke, pulmonary embolism, sepsis, acute perimyocarditis,
      Tako-tsubo, acute heart failure, and tachycardia. There are no guidelines to
      treat patients with elevated cTn levels and no coronary disease. The current
      strategy of treatment of patients with elevated troponin and non-acute coronary
      syndrome involves treating the underlying causes. The aim of this paper is to
      review data from studies of non-ACS patients with acutely elevated troponin who
      in clinical practice may be difficult to discriminate from ACS patients.

PMID- 21169616
TI  - What's new in informatics.

PMID- 21169617
TI  - A new JAMIA.

PMID- 21169618
TI  - Never too old for anonymity: a statistical standard for demographic data sharing
      via the HIPAA Privacy Rule.
AB  - OBJECTIVE: Healthcare organizations must de-identify patient records before
      sharing data. Many organizations rely on the Safe Harbor Standard of the HIPAA
      Privacy Rule, which enumerates 18 identifiers that must be suppressed (eg, ages
      over 89). An alternative model in the Privacy Rule, known as the Statistical
      Standard, can facilitate the sharing of more detailed data, but is rarely applied
      because of a lack of published methodologies. The authors propose an intuitive
      approach to de-identifying patient demographics in accordance with the
      Statistical Standard. DESIGN: The authors conduct an analysis of the demographics
      of patient cohorts in five medical centers developed for the NIH-sponsored
      Electronic Medical Records and Genomics network, with respect to the US census.
      They report the re-identification risk of patient demographics disclosed
      according to the Safe Harbor policy and the relative risk rate for sharing such
      information via alternative policies. MEASUREMENTS: The re-identification risk of
      Safe Harbor demographics ranged from 0.01% to 0.19%. The findings show
      alternative de-identification models can be created with risks no greater than
      Safe Harbor. The authors illustrate that the disclosure of patient ages over the
      age of 89 is possible when other features are reduced in granularity.
      LIMITATIONS: The de-identification approach described in this paper was evaluated
      with demographic data only and should be evaluated with other potential
      identifiers. CONCLUSION: Alternative de-identification policies to the Safe
      Harbor model can be derived for patient demographics to enable the disclosure of
      values that were previously suppressed. The method is generalizable to any
      environment in which population statistics are available.

PMID- 21169619
TI  - Assessing the impact of user-centered research on a clinical trial eHealth tool
      via counterbalanced research design.
AB  - OBJECTIVE: Informatics applications have the potential to improve participation
      in clinical trials, but their design must be based on user-centered research.
      This research used a fully counterbalanced experimental design to investigate the
      effect of changes made to the original version of a website,
      http://BreastCancerTrials.org/, and confirm that the revised version addressed
      and reinforced patients' needs and expectations. DESIGN: Participants included
      women who had received a breast cancer diagnosis within the last 5 years (N=77).
      They were randomized into two groups: one group used and reviewed the original
      version first followed by the redesigned version, and the other group used and
      reviewed them in reverse order. MEASUREMENTS: The study used both quantitative
      and qualitative measures. During use, participants' click paths and general
      reactions were observed. After use, participants were asked to answer survey
      items and open-ended questions to indicate their reactions and which version they
      preferred and met their needs and expectations better. RESULTS: Overall, the
      revised version of the site was preferred and perceived to be clearer, easier to
      navigate, more trustworthy and credible, and more private and safe overall.
      However, users who viewed the original version last had similar attitudes toward
      both versions. CONCLUSION: By applying research findings to the redesign of a
      website for clinical trial searching, it was possible to re-engineer the
      interface to better support patients' decisions to participate in clinical
      trials. The mechanisms of action in this case appeared to revolve around creating
      an environment that supported a sense of personal control and decisional
      autonomy.

PMID- 21169620
TI  - Anticipating and addressing the unintended consequences of health IT and policy:
      a report from the AMIA 2009 Health Policy Meeting.
AB  - Federal legislation (Health Information Technology for Economic and Clinical
      Health (HITECH) Act) has provided funds to support an unprecedented increase in
      health information technology (HIT) adoption for healthcare provider
      organizations and professionals throughout the U.S. While recognizing the promise
      that widespread HIT adoption and meaningful use can bring to efforts to improve
      the quality, safety, and efficiency of healthcare, the American Medical
      Informatics Association devoted its 2009 Annual Health Policy Meeting to
      consideration of unanticipated consequences that could result with the increased
      implementation of HIT. Conference participants focused on possible unintended and
      unanticipated, as well as undesirable, consequences of HIT implementation. They
      employed an input-output model to guide discussion on occurrence of these
      consequences in four domains: technical, human/cognitive, organizational, and
      fiscal/policy and regulation. The authors outline the conference's
      recommendations: (1) an enhanced research agenda to guide study into the causes,
      manifestations, and mitigation of unintended consequences resulting from HIT
      implementations; (2) creation of a framework to promote sharing of HIT
      implementation experiences and the development of best practices that minimize
      unintended consequences; and (3) recognition of the key role of the Federal
      Government in providing leadership and oversight in analyzing the effects of HIT
      related implementations and policies.

PMID- 21169622
TI  - Performance of support-vector-machine-based classification on 15 systematic
      review topics evaluated with the WSS@95 measure.

PMID- 21169624
TI  - AMIA president's message.

PMID- 21169625
TI  - In people with subclinical hypothyroidism, TSH level >10 mIU/l may predict
      increased risk of coronary heart disease and related mortality.

PMID- 21169626
TI  - An automated molecular test for Mycobacterium tuberculosis and resistance to
      rifampin (Xpert MTB/RIF) is sensitive and can be carried out in less than 2 h.

PMID- 21169634
TI  - Perioperative acupuncture and postoperative acupressure can prevent postoperative
      vomiting following paediatric tonsillectomy or adenoidectomy: a pragmatic
      randomised controlled trial.
AB  - OBJECTIVE: To investigate the effectiveness of acupuncture and acupressure as
      supplements to standard treatment for postoperative vomiting in children
      undergoing tonsillectomy and/or adenoidectomy. METHODS: A pragmatic, open, block
      randomised controlled trial. The results were analysed according to the intention
      to-treat principle. The study was conducted without extra resources in a normal
      setting at the day-surgery department of Lovisenberg Diakonale Hospital in Oslo.
      154 children with an American Society of Anesthesiologists grade 1-2, weighing at
      least 10 kg, were included. Children with concomitant gastrointestinal diseases,
      emesis or antiemetic treatment <24 h preoperatively, rash or local infection over
      the actual acupuncture points were excluded together with patients whose parents'
      informed consent could not be obtained. The intervention group received
      acupuncture at pericardium 6 bilaterally, at a depth of approximately 0.7 cm with
      a median of 21 min during anaesthesia, followed by acupressure wristbands for 24
      h and standard treatment. The control group received standard treatment. The
      primary end point was the occurrence of vomiting or retching during 24 h
      postoperatively. RESULTS: Children in the acustimulation group experienced less
      retching and vomiting than the control group-46.8% versus 66.2% (p=0.015). The
      effect of acustimulation was specifically pronounced in girls and children aged 1
      3 years. CONCLUSION: This trial indicates the effectiveness of acustimulation as
      an adjunct to standard treatment. The results should encourage and promote the
      implementation of acustimulation for postoperative vomiting in children
      undergoing adenoidectomy or tonsillectomy.

PMID- 21169635
TI  - Kinesin-73 is a processive motor that localizes to Rab5-containing organelles.
AB  - Drosophila Kinesin-73 (Khc-73), which plays a role in mitotic spindle polarity in
      neuroblasts, is a metazoan-specific member of the Kinesin-3 family of motors,
      which includes mammalian KIF1A and Caenorhabditis elegans Unc-104. The mechanism
      of Kinesin-3 motors has been controversial because some studies have reported
      that they transport cargo as monomers whereas other studies have suggested a
      dimer mechanism. Here, we have performed single-molecule motility and cell
      biological studies of Khc-73. We find that constructs containing the motor and
      the conserved short stretches of putative coiled-coil-forming regions are
      predominantly monomeric in vitro, but that dimerization allows for fast,
      processive movement and high force production (7 piconewtons). In Drosophila cell
      lines, we present evidence that Khc-73 can dimerize in vivo. We also show that
      Khc-73 is recruited specifically to Rab5-containing endosomes through its "tail"
      domain. Our results suggest that the N-terminal half of Khc-73 can undergo a
      monomer-dimer transition to produce a fast processive motor and that its C
      terminal half possesses a specific Rab5-vesicle binding domain.

PMID- 21169636
TI  - Rab27a negatively regulates phagocytosis by prolongation of the actin-coating
      stage around phagosomes.
AB  - Rab27a, a Rab family small GTPase, is involved in the exocytosis of secretory
      granules in melanocytes and cytotoxic T-cells. Rab27a mutations cause type 2
      Griscelli syndrome, which is characterized by immunodeficiency, including
      uncontrolled macrophage activation known as hemophagocytic syndrome. However, the
      role of Rab27a in phagocytosis remains elusive. Here, using macrophage-like
      differentiated HL-60 cells and C3bi-opsonized zymosan as a pathogen-phagocyte
      model, we show that Rab27a negatively regulates complement-mediated phagocytic
      activity in association with F-actin remodeling. We found that transfection of
      Rab27a shRNA into HL-60 cells enhances complement-mediated phagocytosis. To
      clarify the mechanisms underlying the elevated phagocytosis in Rab27a knockdown
      cells, we analyzed the process of phagosome formation focusing on F-actin
      dynamics: F-actin assembly, followed by F-actin extension around the particles
      and the subsequent degradation of F-actin, leading to internalization of the
      particles enclosed in phagosomes. Microscopic analysis revealed that these actin
      related processes, including F-actin coating and F-actin degradation, proceed
      more rapidly in Rab27a knockdown cells than in control HL-60 cells. Both elevated
      phagocytosis and accelerated F-actin remodeling were restored by expression of
      rescue-Rab27a and Rab27a-Q78L (GTP-bound form), but not by Rab27a-T23N (GDP-bound
      form). Furthermore, an increased accumulation of Coronin 1A surrounding F-actin
      coats was observed in Rab27a knockdown cells, suggesting that the function of
      Coronin 1A is related to the regulation of the F-actin coating. Our findings
      demonstrate that Rab27a plays a direct regulatory role in the nascent process of
      phagocytosis by prolongation of the stage of actin coating via suppression of
      Coronin 1A. This study may contribute to an explanation of the underlying
      mechanisms of excessive phagocytosis observed in Griscelli syndrome.

PMID- 21169637
TI  - MMS6 protein regulates crystal morphology during nano-sized magnetite
      biomineralization in vivo.
AB  - Biomineralization, the process by which minerals are deposited by organisms, has
      attracted considerable attention because this mechanism has shown great potential
      to inspire bottom-up material syntheses. To understand the mechanism for
      morphological regulation that occurs during biomineralization, many regulatory
      proteins have been isolated from various biominerals. However, the molecular
      mechanisms that regulate the morphology of biominerals remain unclear because
      there is a lack of in vivo evidence. Magnetotactic bacteria synthesize
      intracellular magnetosomes that comprise membrane-enveloped single crystalline
      magnetite (Fe(3)O(4)). These nano-sized magnetite crystals (<100 nm) are
      bacterial species dependent in shape and size. Mms6 is a protein that is tightly
      associated with magnetite crystals. Based on in vitro experiments, this protein
      was first implicated in morphological regulation during nano-sized magnetite
      biomineralization. In this study, we analyzed the mms6 gene deletion mutant
      (Deltamms6) of Magnetospirillum magneticum (M. magneticum) AMB-1. Surprisingly,
      the Deltamms6 strain was found to synthesize the smaller magnetite crystals with
      uncommon crystal faces, while the wild-type and complementation strains
      synthesized highly ordered cubo-octahedral crystals. Furthermore, deletion of
      mms6 gene led to drastic changes in the profiles of the proteins tightly bound to
      magnetite crystals. It was found that Mms6 plays a role in the in vivo regulation
      of the crystal structure to impart the cubo-octahedral morphology to the crystals
      during biomineralization in magnetotactic bacteria. Magnetotactic bacteria
      synthesize magnetite crystals under ambient conditions via a highly controlled
      morphological regulation system that uses biological molecules.

PMID- 21169638
TI  - Hedgehog signaling induced by breast cancer cells promotes osteoclastogenesis and
      osteolysis.
AB  - Bone integrity is maintained by a dynamic equilibrium between the activities of
      bone-forming osteoblasts and bone-resorbing osteoclasts. Osteolytic lesions are a
      painful consequence of metastasis of breast cancer cells to bone in an
      overwhelming majority of breast cancer patients. Factors secreted by breast
      cancer cells propel a cascade of events that trigger osteoclastogenesis and
      elevated bone resorption. In the present study, we show that the Hedgehog (Hh)
      ligands secreted by breast cancer cells promote osteoclast differentiation and
      potentiate the activity of mature osteoclasts. Paracrine Hh signaling induced by
      breast cancer cells mediates a detrimental chain of events by the up-regulation
      of osteopontin (OPN), which in turn enhances osteoclastic activity by up
      regulating cathepsin K and MMP9. Hh signaling is essential for osteoclasts
      because blocking the Hh pathway using the pharmacological Hh inhibitor,
      cyclopamine, results in an overall decrease in osteoclastogenesis and resorptive
      activity. Our studies suggest that inhibiting Hh signaling interferes with the
      ability of pre-osteoclasts to respond to the stimulatory effects of the breast
      cancer cells, indicating that Hh signaling is vital to osteoclast activity.

PMID- 21169639
TI  - Expression of heparan sulfate in gastric carcinoma and its correlation with
      clinicopathological features and patient survival.
AB  - AIM: To determine the expression pattern and prognostic value of heparan sulfate
      in gastric cancer. METHOD: The 10E4 antiheparan sulfate monoclonal antibody was
      used to examine the expression pattern of heparan sulfate in tissue microarrays
      consisting of 162 cases of gastric carcinoma by immunohistochemistry. The
      immunoreactivities of both epithelial and stromal components of the specimens
      were examined and analysed statistically for significant associations with
      clinicopathological parameters, including histological grade of the tumour,
      extent of cancer infiltration and presence of lymph-node metastases,
      lymphovascular invasion, perineural invasion, perforation of gastric wall and
      stromal reaction. The potential use of heparan sulfate as a predictive factor for
      patient survival was also evaluated. RESULTS: Reduced expression of heparan
      sulfate in the epithelial component was associated with higher histological
      grades of gastric cancer as well as the presence of more extensive tumour
      infiltration. Furthermore, this decrease in heparan sulfate expression was found
      to be predictive of reduced patient survival after tumour recurrence. CONCLUSION:
      The data suggest that heparan sulfate may play an important role in regulating
      the biology of gastric cancer, and that it may be a useful prognostic marker of
      this tumour.

PMID- 21169640
TI  - Effect of high-dose phenobarbital on oxidative stress in perinatal asphyxia: an
      open label randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effect of high dose phenobarbital on lipid
      peroxidation and antioxidant enzymes in perinatal asphyxia. DESIGN: Open label,
      Randomized controlled trial. SETTING: Neonatal intensive care unit of a tertiary
      care teaching hospital. PARTICIPANTS: 72 full term inborn neonates with severe
      birth asphyxia. METHODS: Neonates were randomized to Study (phenobarbital) group
      and Control group. The infants in the study group received phenobarbital infusion
      (40 mg/kg) within first two hours of life while babies in the control group did
      not receive any phenobarbital. Rest of the management in both the groups was as
      per the unit protocol for the management of hypoxic ischemic encephalopathy. A
      cerebrospinal fluid examination was done at 12 +/- 2 hours of life to determine
      the levels of superoxide dismutase, glutathione peroxidise and malonyldialdehyde.
      60 neonates were followed up at 1 month of age when a detailed neurological
      examination was done. RESULTS: Four neonates in the study group and six neonates
      in the control group died during the study. Two neonates in the study group were
      lost to follow up. The cerebrospinal fluid lipid peroxides and antioxidant
      enzymes were significantly lower in the phenobarbital group as compared to the
      control group. The neurological outcome at one month follow up was found to be
      comparable between the two groups. CONCLUSION: Phenobarbital (40 mg/kg) given in
      the first two hours of life in term neonates with perinatal asphyxia led to a
      decrease in CSF levels of lipid peroxides and antioxidant enzymes at 12 +/- 2
      hours of life.

PMID- 21169641
TI  - Evaluation of phototherapy devices used for neonatal hyperbilirubinemia.
AB  - OBJECTIVE: To compare phototherapy devices based on their physical and photo
      biological characteristics viz spectral properties, maximum and mean irradiance,
      treatable percentage of body surface area, decay of irradiance over time and in
      vitro photoisomerisation of bilirubin. DESIGN: In vitro experimental study.
      SETTING: Ocular pharmacy laboratory at a tertiary care hospital. METHODLOGY: All
      the characteristics were measured at a fixed distance of 35 cm from one compact
      fluorescent lamp (CFL) and three light emitting diode (LED) phototherapy devices
      in a dark room with an irradiance of <0.1uW/cm2/nm. Estimation of products of in
      vitro photoisomerisation was done using liquid chromatography - tandem mass
      spectroscopy (LC-MS/MS). RESULTS: The emission spectral data were comparable
      between the phototherapy devices. The devices, however, differed in their maximum
      irradiance with the spot and indigenous LED units having the highest and lowest
      values, respectively (56.5 and 16.8uW/cm2/nm). The mean irradiance measured in
      5x5cm grids falling within the silhouette of a term baby of the spot and
      improvised LED devices were low (26.8uW/cm2/nm and 11.5uW/cm2/nm, respectively)
      possibly due to unevenness in the irradiance of light falling within the
      silhouette. There was a significant difference in the amount of bilirubin left
      after exposure to light over a 2hour time period (% reduction of bilirubin) among
      the four devices (P=0.001); at 120 minutes after exposure, the amount of
      bilirubin left was lowest for the CFL (16%) and spot LED (17%) devices and
      highest for the indigenous LED unit (41%). CONCLUSIONS: The four phototherapy
      devices differed markedly in their physical and photobiological characteristics.
      Since the efficacy of a device is dependent not only on the maximum irradiance
      but also on the mean irradiance, rate of decay of irradiance, and treatable
      surface area of the foot print of light, each phototherapy device should have
      these parameters verified and confirmed before being launched for widespread use.

PMID- 21169642
TI  - Iodine deficiency disorders in 6-12 years old rural primary school children in
      Kutch district, Gujarat.
AB  - OBJECTIVE: To compare prevalence of goitre in primary school children; to
      determine median urinary iodine concentration in children; and, to assess level
      of salt iodization at retail trader level. DESIGN: 30 cluster survey study.
      SETTINGS: Primary schools of Kutch district, Gujarat, India. METHODS: Total 70
      students including five boys and five girls from 1st to 7th standard, present in
      class on the day of visit were selected randomly for Goitre examination (n=2100).
      Urine sample was collected from one boy and one girl from each standard in each
      cluster. From the community, 28 children, including two boys and two girls from
      each standard in the same age group were examined, and salt samples were tested
      from their households. From each village, one retail shop was visited and various
      salts available were purchased and tested for iodine on the spot with spot kit.
      RESULTS: Goitre prevalence of 11.2% was found among primary school children
      (grade 1- 8.6% and grade 2-2.6%). As the age increased, the Goitre prevalence
      also increased except in age group of 8 years. Median urinary iodine excretion
      level was 110 ug/L. Iodine level more than 15 ppm was found in 92.3% salts
      samples tested at the household level. CONCLUSION: Present study showed mild
      goitre prevalence in primary school children in Kutch district of Gujarat.

PMID- 21169643
TI  - Whole body cooling in newborn infants with perinatal asphyxial encephalopathy in
      a low resource setting: a feasibility trial.
AB  - OBJECTIVE: To determine the feasibility and safety of whole body cooling in
      newborn infants with perinatal asphyxial encephalopathy in a low resource
      setting. DESIGN: Feasibility trial. SETTING: Tertiary care perinatal centre.
      SUBJECTS: Infants born at > 35 weeks gestation with perinatal asphyxia were
      included in the study. INTERVENTIONS: Infants were cooled to a rectal temperature
      of 33 +/- 0.5 degrees C for 72 hours using cloth-covered ice-gel packs. Vital
      parameters were monitored continuously. OUTCOME MEASURES: The primary outcome was
      the achievement of target temperature within 1 hour of initiation of treatment
      and maintaining the target temperature for 72 hours. Adverse events and possible
      complications of hypothermia were the secondary outcomes measured. RESULTS:
      Twenty infants were included in the study. The mean time taken to achieve target
      rectal temperature was 52 +/- 25 minutes. The mean rectal temperature during
      cooling was 32.9 +/- 0.11oC. The target temperature could be maintained for 72
      hours without difficulty in all babies. Adverse events observed during cooling
      were thrombocytopenia (25%), sinus bradycardia (25%), deranged bleeding
      parameters (20%), aposteatonecrosis (15%), hyperglycemia (15%), hypoglycemia
      (10%), hypoxemia (5%), life-threatening coagulopathy (5%) and death (5%).
      Shivering was noted in many of the babies, especially in the initial phase of
      cooling. CONCLUSION: Whole body cooling in term infants with perinatal asphyxia
      is achievable, safe and inexpensive in a low-resource setting.

PMID- 21169644
TI  - Early rescue administration of surfactant and nasal continuous positive airway
      pressure in preterm infants <32 weeks gestation.
AB  - OBJECTIVE: This study reports our institutional experience on the outcome after
      prophylactic and early rescue endotracheal instillation of surfactant within 20
      minutes of birth, followed by extubation and nasal continuous positive airway
      pressure (NCPAP) in preterm infants <32 weeks gestational age. PATIENTS AND
      METHODS: A total of 142 infants were prospectively studied (42, gestational age
      from 23 to 27 and 100, from 28 up to 32 weeks). All infants were electively
      intubated for administration of 200 mg/kg porcine isolated surfactant (Curosurf,
      Chiesi Farmaceutici SPA, Parma, Italy) as soon as practicably possible (within 20
      min after birth) and NCPAP was then initiated. RESULTS: Extubation and switch to
      NCPAP at 6 h was successful in 6/42 (14.3%) infants less than 28 weeks
      gestational age and 75/100 (75%) infants 28-32 weeks gestational age. Out of 81
      infants that were successfully extubated, 76 (93.83%) never required re
      ventilation. At 96 h of age, need for continuing intubation and ventilation was
      required by 6/38 (15.8%) alive infants <28 weeks gestational age and 8/100 (8%)
      infants 28-32 weeks gestational age. Mean duration of NCPAP post-extubation was
      38+/-20 hours for infants 23-27 wks and 29+/-15 hours for infants 28-32 wks
      gestational age. The mortality rate was 2.81% (4/142). CONCLUSION: Implementation
      of prophylactic or early rescue administration of surfactant with NCPAP in
      infants at high risk for developing RDS in neonatal ICU is a safe modality of
      respiratory support in preterm infants.

PMID- 21169645
TI  - Growth pattern of schoolchildren in Sagamu, Nigeria using the CDC standards and
      2007 WHO standards.
AB  - OBJECTIVE: To compare the median weight, height and body mass index of school
      children with the 2000 CDC and 2007 WHO reference values. SETTINGS:
      Schoolchildren in Sagamu, Nigeria. DESIGN: Cross-sectional survey. METHODS:
      Between November and December, 2008, 1690 school children aged 6 to 16 years from
      8 primary schools were surveyed using multi-stage sampling methods. The weight,
      height and body mass index (BMI) were recorded for each child. The Z-scores of
      the median anthropometric parameters for each age and sex were determined with
      the LMS statistical method using the values of L, M and S provided on the CDC and
      WHO charts. RESULTS: The weight, height and BMI Z-scores were less than the
      reference values provided on the CDC and WHO charts but were generally closer to
      the WHO standards compared to the CDC standards. The median weight, height and
      BMI for females generally plotted higher on CDC and WHO chart compared to the
      males. The prevalence of underweight and stunting were relatively lower while the
      prevalence of overweight and obesity was relatively higher among children aged 6
      to 10 years using the WHO references compared to the CDC reference values.
      CONCLUSIONS: The WHO references would under-diagnose under-nutrition and over
      diagnose overweight/obesity in the population studied.

PMID- 21169646
TI  - Evaluation of cardiac iron load by cardiac magnetic resonance in thalassemia.
AB  - OBJECTIVE: To quantify myocardial iron stores by Cardiac Magnetic Resonance
      (CMR). DESIGN: Prospective cohort study. SETTING: Thalassemia center in a
      teaching hospital. PARTICIPANTS: 60 transfusion dependant thalassemia major
      patients and 10 controls during 2008-2009. METHODS: MRI T2* for cardiac iron load
      and cardiac functions was performed on a 1.5 Tesla Siemens Sonata machine using
      the thalassemia tools software. Ejection fraction (EF) was measured using
      standard CMR sequence and EF <56% considered as cardiac dysfunction.
      Quantification of iron deposition was categorized as T2* <10 milliseconds (ms) as
      high risk, 10-20 ms as intermediate risk and >20 ms as low risk. Simultaneous
      liver iron T2* values were categorized into normal i.e. >6.3 ms, mild iron
      overload 6.3-2.7 ms , moderate iron overload 2.7- 1.4 ms and severe iron overload
      <1.4 ms. Pretransfusion serum ferritin levels were simultaneously determined.
      Data was analyzed by paired and unpaired t test of mean. RESULTS: Of 60 patients,
      50% had no cardiac siderosis; 33.3% had mild to moderate and while 16.7% had
      severe cardiac siderosis . In contrast, only 8.3% had normal liver iron values,
      55.7% had mild to moderate and 36% had severe iron stores. The mean serum
      ferritin of all 60 cases was 3528.6 +/- 1958.6 ng/mL. There was a statistically
      significant difference in the mean cardiac T2* of patients (23.45 +/- 13.4 ms) as
      compared to controls (32.67 +/- 2.68 ms) (P<0.01). CONCLUSIONS: Thalassemia
      patients had significantly higher cardiac iron stores as compared to controls.
      Serum ferritin and liver iron values did not correlate with cardiac iron values.
      Three of 10 patients <10 years showed evidence of myocardial siderosis.

PMID- 21169647
TI  - Early neonatal morbidities in late preterm infants.
AB  - OBJECTIVES: To compare early neonatal morbidity (within first 7 days of life) in
      late preterm infants with term infants. STUDY DESIGN: Prospective cohort study.
      SUBJECTS: All live inborn late preterm infants (34 0/7 to 36 6/7 weeks) and term
      infants (37 0/7 to 41 6/7 weeks). OUTCOME: Any of the predefined medical
      conditions listed in the study, resulting in post- delivery inpatient hospital
      observation, admission, or readmission in first 7 days of life. RESULTS: 363 late
      preterm infants and 2707 term infants were included in study. Two hundred fifty
      seven (70.8 %) of late preterm and 788 (29.1%) of term infants had at least one
      of the predefined neonatal conditions. Late preterm infants were at significantly
      higher risk for overall morbidity due to any cause (P<0.001; adjusted Odds Ratio
      (OR): 5.5; 95% CI: 4.2-7.1), respiratory morbidity (P<0.001; adjusted OR: 7.5;
      95% CI: 4.2-12.3), any ventilation (non invasive or invasive) (P=0.001; adjusted
      OR: 4.2; 95% CI: 2-8.9), jaundice (P<0.001; adjusted OR: 3.4; 95% CI: 2.7-4.4),
      hypoglycemia (P<0.001; adjusted OR: 4.5; 95% CI: 2.6-7.7), and probable sepsis
      (P<0.001; adjusted OR: 3.2; 95% CI: 1.6-6.5). The incidence of morbidities
      increased from 23% at 40 weeks to 30%, 39.7%, 67.5%, 89% and 87.9% at 38, 37, 36,
      35 and 34 weeks, respectively (P<0.001). CONCLUSION: Compared with term infants,
      late preterm infants are at high risk for respiratory morbidity, need of
      ventilation (non invasive or invasive), jaundice, hypoglycemia, sepsis, and
      probable sepsis. All gestations except 39 weeks were at significantly higher risk
      for morbidity with 40 weeks as reference term.

PMID- 21169648
TI  - Ewing sarcoma of the clavicle: a case series.
AB  - Clavicle is a rare primary site for Ewing sarcoma (ES). We analyzed 4 patients
      with clavicular ES under our follow up and reviewed the literature on management
      of this rare tumor. All our patients were females with a median age of 16 years
      and were non metastatic at presentation. After a median follow-up of 21.5 months,
      3 out of 4 patients are in complete remission. Clavicular ES in contrast to ES of
      other sites seems to have a female preponderance and outcomes are similar to non
      metastatic ES of other common sites.

PMID- 21169649
TI  - Behavioral correlates of television viewing in young adolescents in Turkey.
AB  - We evaluated the behavioral effects of television (TV) viewing in 860 young
      adolescents as reported by parents (n=581) on Child Behavior Checklist (CBCL).
      The mean duration of TV viewing was 2.32 +/- 1.77 hours/day according to parents
      and 2.08 +/- 1.41 hours/day according to self report (r=0.37, P <0.0001). The
      linear regression analysis revealed a statistically significant relation between
      socioeconomic status (P=0.019) and aggressive behavior score of CBCL (P=0.016)
      and parent reported TV viewing hours. Self reported TV viewing for more than 2
      hours was significantly associated with social problem score (OR 1.17; 95%
      CI:1.016-1.349; P=0.030) and having a TV in bedroom (OR:1.706; 95% ;CI: 1.065
      2.731, P=0.026).

PMID- 21169650
TI  - Persisting malnutrition in Chandigarh: decadal underweight trends and impact of
      ICDS program.
AB  - Decline in malnutrition levels has been dismal since the 1990s. We ascertained
      decadal trend in childhood nutritional status between 1997 and 2007 in
      Chandigarh, India and assessed impact of Integrated Child Development Services
      (ICDS) on childhood undernutrition. A total of 803 under-five children, 547
      children between 12-23 months age, and 218 women with an infant child were
      recruited for the study. Findings of present study were compared with another
      methodologically similar study (1997) from Chandigarh and Reproductive and Child
      Health Rapid Household Survey (1998) to draw decadal trends. Prevalence of
      underweight among under-five children remained almost stagnant in the last one
      decade from 51.6%; (1997) to 50.4%; (2007). There was insignificant difference
      (P=0.3) in prevalence of underweight among children registered under ICDS program
      (52.1%;) and those not registered (48.4%;) in 2007. Other health and service
      provision indicators had mixed results in the past decade. Health services
      utilization was poorest in urban slums.

PMID- 21169651
TI  - Quality assessment of systematic reviews of health care interventions using
      AMSTAR.
AB  - Appraisal of the methodological quality of systematic reviews would reflect on
      their utility for the clinicians and policymakers. This study was done to assess
      the quality of systematic reviews published in five leading Indian medical
      journals using AMSTAR. 22 systematic reviews of healthcare interventions were
      identified. The scores ranged 0 to 10 (mean 3.77 and median 2.5), 9 reviews
      scored > 4/11. Most frequent yes and no scores were: publication status as an
      inclusion criterion (12 /22), respectively and duplicate study selection and data
      extraction (17 /22). Several suboptimal aspects of methodological quality were
      identified in the reviews evaluated.

PMID- 21169652
TI  - Sleep problems in preschool and school aged rural Indian children.
AB  - We assessed 513 children (2-6 y = 252; 7-12 y = 261) who visited the pediatric
      outpatient of a rural medical college hospital, for sleep problems using BEARS
      tool. Sleep problems detected in the BEARS domains for preschool (2-6 years,
      n=252) and school children (7-12 years, n=261) were as follows: bedtime problems
      (33.3%vs 14.9% P< 0.001), excessive daytime sleepiness (32.5%vs 1.9% P<0.001),
      awakening during night (25%vs 11.87% P< 0.001), regularity and duration of sleep
      (19.84% vs 4.98% P< 0.001), and sleep disordered breathing (4.8% vs 5% , P=0.1).
      We conclude that sleep problems are common among rural Indian children and should
      be routinely screened for during health visits.

PMID- 21169653
TI  - Food security and anthropometric failure among tribal children in Bankura, West
      Bengal.
AB  - We conducted a cross-sectional study among 188 tribal children aged 6-59 months
      using two-stage sampling in Bankura-I Block of Bankura district, West Bengal,
      India, to assess their nutritional status and its relation with household food
      security. Weight and height/length were measured and analyzed as per new WHO
      Growth Standards. Mothers of the study children were interviewed to obtain
      relevant information. Prevalence of Composite Index of Anthropometric Failure was
      69.1%; and multiple anthropometric failures were more likely among tribal
      children aged 24-59 months with irregular utilization of supplementary nutrition
      and from households with severe grades of food security.

PMID- 21169654
TI  - Prevalence of psychiatric morbidity in visually impaired children.
AB  - This study was done to measure psychiatric morbidity and associated
      sociodemographic variables among visually impaired children. 92 students of age
      range 6 to 20 years from four schools for the blind, in Ranchi, were screened
      with verbal Hindi translation of General Health Questionnaire 60. Diagnostic
      Interview Schedule Parent version was applied to establish psychiatric diagnosis
      on primary caretakers of those who scored above cutoff. Fourteen scored above cut
      off and psychiatric diagnoses of 8 children were established. The prevalence of
      psychiatric morbidity among visually impaired children was found to be 8.69% No
      sociodemographic variable was associated with the occurrence of psychiatric
      illness.

PMID- 21169655
TI  - Immunogenicity of single dose live attenuated hepatitis a vaccine.
AB  - A long-term immunogenicity study of a single dose live attenuated H2 strain
      hepatitis A vaccine is being conducted in healthy Indian children at KEM
      Hospital, Pune. 131 of the original 143 children vaccinated in 2004, were
      evaluated for anti-HAV antibodies 30 months post vaccination (2007).
      Seroprotective antibody levels >20 mIU/mL were demonstrated in 87.8 % subjects
      with an overall GMT of 92.02 mIU/mL. No hepatitis like illness was recorded in
      any of the subjects since vaccination.

PMID- 21169656
TI  - Magnetic nanoparticle-based separation of metallic and semiconducting carbon
      nanotubes.
AB  - We report a simple and scalable method for the separation of semiconducting
      single-walled carbon nanotubes (SWNTs) from metallic SWNTs using magnetic
      nanoparticles (MNPs) functionalized with polycationic tri-aminated polysorbate 80
      (TP80). MNPs-TP80 are selectively adsorbed on acid-treated semiconducting SWNTs,
      which makes the semiconducting SWNTs be highly concentrated to over 95% under a
      magnetic field. Almost all the field effect transistor network devices, which
      were fabricated using separated semiconducting SWNTs, exhibited a p-type
      semiconducting behavior with an on/off ratio of higher than 10(4).

PMID- 21169657
TI  - A simple and efficient method to prepare graphene by reduction of graphite oxide
      with sodium hydrosulfite.
AB  - Inspired by an ancient reducing method used in textile production, sodium
      hydrosulfite was used to reduce graphite oxide as an efficient reducing agent in
      our work. The reduced materials were characterized by x-ray photoelectron
      spectroscopy, thermogravimetric analysis, wide-angle x-ray scattering, Raman
      spectroscopy, solid state (13)C NMR spectroscopy and electrical conductivity
      measurements, respectively. The results showed that graphite oxide can be reduced
      with sodium hydrosulfite in a few minutes, with a degree of reduction comparable
      to those achieved with hydrazine. It provides an efficient method to reduce
      graphite oxide and could be used as a method to prepare novel composites.

PMID- 21169658
TI  - The fabrication of large-area, free-standing GaN by a novel nanoetching process.
AB  - A simple yet versatile nanoetching process in porosifying and 'machining' GaN is
      reported in this work. By combining different porosifying conditions through
      potentiostatic modulation or embedding doping design, we are able to separate and
      lift off GaN layers over a macroscopic area (>=cm(2)). Strain relaxation and
      single crystallinity are confirmed by Raman and transmission electron microscopy,
      respectively. This method is expected to open up a new dimension in epitaxy,
      design and manufacture of GaN heterostructures and devices.

PMID- 21169659
TI  - The enhanced microwave absorption property of CoFe(2)O(4) nanoparticles coated
      with a Co(3)Fe(7)-Co nanoshell by thermal reduction.
AB  - CoFe(2)O(4) nanoparticles were fabricated by a sol-gel method and then were
      coated with Co(3)Fe(7)-Co by means of a simple reduction process at different
      temperatures under 2% H(2) with the protection of argon to generate the
      dielectric-core/metallic-shell structure. The optimum reflection loss (RL)
      calculated from permittivity and permeability of the 80 wt%
      CoFe(2)O(4)/Co(3)Fe(7)-Co and 20 wt% epoxy resin composites reached - 34.4 dB,
      which was much lower than that of unreduced CoFe(2)O(4) and epoxy resin
      composites, at 2.4 GHz with a matching thickness of 4.0 mm. Moreover the RL
      exceeding - 10 dB in the maximum frequency range of 2.2-16 GHz was achieved for a
      thickness of composites of 1.0-4.5 mm with 600  degrees C thermal reduction
      process. The improved microwave absorption properties are a consequence of a
      proper electromagnetic match and the enhanced magnetic loss besides its
      dielectric loss due to the existence of the core/shell structure in CoFe(2)O(4)
      composites. Thus, the reductive CoFe(2)O(4) nanoparticles have great potential
      for being a highly efficient microwave absorber.

PMID- 21169660
TI  - The controlled fabrication and geometry tunable optics of gold nanotube arrays.
AB  - Arrays of vertically aligned gold nanotubes are fabricated over several square
      centimetres which display a geometry tunable plasmonic extinction peak at visible
      wavelengths and at normal incidence. The fabrication method gives control over
      nanotube dimensions with inner core diameters of 15-30 nm, wall thicknesses of 5
      15 nm and nanotube lengths of up to 300 nm. It is possible to tune the position
      of the extinction peak through the wavelength range 600-900 nm by varying the
      inner core diameter and wall thickness. The experimental data are in agreement
      with numerical modelling of the optical properties which further reveal highly
      localized and enhanced electric fields around the nanotubes. The tunable nature
      of the optical response exhibited by such structures could be important for
      various label-free sensing applications based on both refractive index sensing
      and surface-enhanced Raman scattering.

PMID- 21169661
TI  - A surfactant-free recipe for shape-controlled synthesis of CdSe nanocrystals.
AB  - We described surfactant-free recipes for the synthesis of CdSe nanocrystals (NCs)
      with well-controlled morphologies at a relatively low temperature. Dot-, rod-,
      tetrapod-and sphere-shaped CdSe NCs were prepared with trioctylphosphine oxide
      (TOPO) as a non-equilibrium solvent and trioctylphosphine selenide (TOPSe) and
      cadmium carboxylates as Se and Cd precursors, respectively. It was found that the
      morphology and stacking pattern of the CdSe NCs were related to the preparation
      conditions such as the concentration of the injected TOPSe(monomer
      concentration), reaction temperature and chain length of the cadmium carboxylate
      precursors. At a reaction temperature of 240  degrees C, CdSe NCs with a tetrapod
      selectivity of up to 85% were obtained in the presence of cadmium myristate under
      high concentrated TOPSe injection, and the in situ-formed myristic acid supplied
      the best acidic ligand with optimal amount to stabilize the anisotropic growth of
      the tetrapods. The intentional addition of more myristic acid in the reaction
      system would block the growth pathway of the tetrapods. Using cadmium laurate,
      cadmium palmitate and cadmium stearate as the cadmium precursors would reduce the
      formation of the tetrapods, showing the very low selectivity of the tetrapods.

PMID- 21169662
TI  - Optimizing flurbiprofen-loaded NLC by central composite factorial design for
      ocular delivery.
AB  - The purpose of this study was to design and optimize a new topical delivery
      system for ocular administration of flurbiprofen (FB), based on lipid
      nanoparticles. These particles, called nanostructured lipid carriers (NLC), were
      composed of a fatty acid (stearic acid (SA)) as the solid lipid and a mixture of
      Miglyol((r)) 812 and castor oil (CO) as the liquid lipids, prepared by the hot
      high pressure homogenization method. After selecting the critical variables
      influencing the physicochemical characteristics of the NLC (the liquid lipid
      (i.e. oil) concentration with respect to the total lipid (cOil/L (wt%)), the
      surfactant and the flurbiprofen concentration, on particle size, polydispersity
      index and encapsulation efficiency), a three-factor five-level central rotatable
      composite design was employed to plan and perform the experiments. Morphological
      examination, crystallinity and stability studies were also performed to
      accomplish the optimization study. The results showed that increasing cOil/L
      (wt%) was followed by an enhanced tendency to produce smaller particles, but the
      liquid to solid lipid proportion should not exceed 30 wt% due to destabilization
      problems. Therefore, a 70:30 ratio of SA to oil (miglyol + CO) was selected to
      develop an optimal NLC formulation. The smaller particles obtained when
      increasing surfactant concentration led to the selection of 3.2 wt% of Tween((r))
      80 (non-ionic surfactant). The positive effect of the increase in FB
      concentration on the encapsulation efficiency (EE) and its total solubilization
      in the lipid matrix led to the selection of 0.25 wt% of FB in the formulation.
      The optimal NLC showed an appropriate average size for ophthalmic administration
      (228.3 nm) with a narrow size distribution (0.156), negatively charged surface (
      33.3 mV) and high EE (~90%). The in vitro experiments proved that sustained
      release FB was achieved using NLC as drug carriers. Optimal NLC formulation did
      not show toxicity on ocular tissues.

PMID- 21169663
TI  - Precise slit-width control of niobium apertures for superconducting LEDs.
AB  - We introduce a novel three-step procedure for precise niobium (Nb)-etching on the
      nanometer-scale, including the design of high contrast resist patterning and
      sacrifice layer formation under high radio frequency (RF) power. We present the
      results of precise slit fabrication using this technique and discuss its
      application for the production of superconducting devices, such as superconductor
      semiconductor-superconductor (S-Sm-S) Josephson junctions. For the reactive ion
      etching (RIE) of Nb, we selected CF(4) as etchant gas and a positive tone resist
      to form the etching mask. We found that the combination of resist usage and RIE
      process allows for etching of thicker Nb layers when utilizing the opposite
      dependence of the etching rate (ER) on the CF(4) pressure in the case of Nb as
      compared to the resist. Precise slit-width control of 80 and 200 nm thick Nb
      apertures was performed with three kinds of ER control, for the resist, the Nb,
      and the underlying layer. S-Sm-S Josephson junctions were fabricated with lengths
      as small as 80 nm, which can be considered clean and short and thus exhibit
      critical currents as high as 50 uA. Moreover, possible further applications, such
      as for apertures of superconducting light emitting diodes (SC LEDs), are
      addressed.

PMID- 21169664
TI  - A study of graphene films synthesized on nickel substrates: existence and origin
      of small-base-area peaks.
AB  - Large-area graphene films, synthesized by the chemical vapor deposition (CVD)
      method, have the potential to be used as electrodes. However, the electrical
      properties of CVD-synthesized graphene films fall short of the best results
      obtained for graphene films prepared by other methods. Therefore, it is important
      to understand the reason why these electrical properties are inferior to improve
      the applicability of CVD-grown graphene films. Here, we show that CVD-grown
      graphene films on nickel substrates contain many small-base-area (SBA) peaks that
      scatter conducting electrons, thereby decreasing the Hall mobility of charges in
      the films. These SBA peaks were induced by small peaks on the nickel surface and
      are likely composed of amorphous carbon. The formation of these SBA peaks on
      graphene films was successfully suppressed by controlling the surface morphology
      of the nickel substrate. These findings may be useful for the development of a
      CVD synthesis method that is capable of producing better quality graphene films
      with large areas.

PMID- 21169665
TI  - Performance of plantar pressure measurement devices (PMDs): update on consensus
      activities.
AB  - A worldwide scientific discussion has been started in 2010 on the need for
      standardisation, assessment, and delivery of recommendations in the field of
      plantar pressure distribution measurement at different levels: hardware
      performance, measuring protocols, data processing, parameters and indicators in
      diagnosis and therapy. The Italian National Institute of Health (Istituto
      Superiore di Sanita, ISS) has been conducting for years a scientific project and
      several activities aimed to design, validate and implement dedicated testing
      methods and recommendations in the field of pressure measurement devices (PMDs).
      The present commentary contains a summary of the activities conducted up to now
      and some future steps which are going to be done at an international level.

PMID- 21169666
TI  - Male circumcision as strategy for HIV prevention and sexually transmitted
      diseases. The potential role of traditional birth attendants in neonatal male
      circumcision.
AB  - In developing countries, it would be advisable to give priority to human
      immunodeficiency virus (HIV) prevention strategies, because of the high mortality
      caused by the rapid spread of the pandemic. Furthermore, HIV prevention could
      contribute to the mitigation of tuberculosis (TB) propagation, which is tightly
      correlated to acquired immune deficiency syndrome (AIDS). As demonstrated, male
      circumcision (MC) confers protection against HIV and sexually transmitted
      diseases (STD). The suggested strategy considers the neonatal MC advantageous,
      since it is safer, feasible, culturally more acceptable and less costly than
      adult MC. This approach is based on the assumption that, if newborn males are
      circumcised, within the next 15-20 years the sexually active population will be
      almost entirely circumcised and, consequently, the HIV transmission will be
      reduced. The employment of retrained traditional birth attendants is considered
      in order to implement the MC after the child birth and to facilitate its
      acceptance in those contexts where it is not traditionally performed.

PMID- 21169667
TI  - No evidence of increased risk of soft tissue sarcomas in the neighborhood of a
      steel foundry in Verona.
AB  - The aim of the present study was to evaluate the possible association between
      occurrence of soft tissue sarcomas in Verona (Italy) and residence near a steel
      foundry, whose emissions of dioxin-like compounds may be relevant. Exposure to
      total suspended particulate (TSP) emitted from the plant as estimated by ADMS
      urban dispersion model was used as an indirect index of exposure to dioxin-like
      compounds. Verona municipality was divided in six subareas according to the
      decreasing levels of estimated TSP exposure, and soft tissue sarcomas cases were
      mapped according to residence at time of diagnosis. Standardized incidence ratios
      were computed. No statistically significant departures between observed and
      expected cases were detected as illustrated by trend-test results.

PMID- 21169668
TI  - A case of contact dermatitis to dimethylfumarate in shoes identified in Italy.
AB  - The present paper describes a case of shoe contact dermatitis from DMF identified
      by the Poison Control Centre of Milan (PCCM), Italy, in 2009. A 35 year old woman
      was affected by irritant reactions while wearing shoes contaminated with DMF.
      Exposure to these shoes was limited to a 8 hour period and was not repeated. In
      the following days the patient suffered feet blistering and swelling limited to
      the area in contact with shoe vamp. Topical application of cortisone did not
      prevent development of bullous eczema. After 20 days from exposure, the lesions
      were healed but the skin remained red, dry and very sensitive. Chemical analyses
      of shoes quantified an average concentration of DMF of 383 mg/kg. The patient
      refused to be patch tested. The observation here reported confirm that DMF should
      be considered a possible causal agent in shoe contact dermatitis. Documentation
      of cases exposed to this chemical provide a relevant support to characterize
      clinical manifestations and to identifying contaminated articles.

PMID- 21169669
TI  - Plants and parts of plants used in food supplements: an approach to their safety
      assessments.
AB  - In Italy most herbal products are sold as food supplements and are subject only
      to food law. A list of about 1200 plants authorised for use in food supplements
      has been compiled by the Italian Ministry of Health. In order to review and
      possibly improve the Ministry's list an ad hoc working group of Istituto
      Superiore di Sanita was requested to provide a technical and scientific opinion
      on plant safety. The listed plants were evaluated on the basis of their use in
      food, therapeutic activity, human toxicity and in no-alimentary fields. Toxicity
      was also assessed and plant limitations to use in food supplements were defined.

PMID- 21169670
TI  - Selenium status and over-expression of interleukin-15 in celiac disease and
      autoimmune thyroid diseases.
AB  - In celiac disease (CD), for its multifactorial nature, the target organs are not
      limited to the gut, but include thyroid, liver, skin and reproductive and nervous
      systems. Between the extraintestinal symptoms associated with CD, autoimmune
      thyroid diseases (AITDs) are more evident, underlining as CD-related autoimmune
      alterations can be modulated not only by gluten but also by various concurrent
      endogenous (genetic affinity, over-expression of cytokines) and exogenous
      (environment, nutritional deficiency) factors. In their pathogenesis a central
      role for over-expression of interleukin-15 (IL-15) is shown, by inhibiting
      apoptosis, leading to the perpetuation of inflammation and tissue destruction.
      Thyroid is particularly sensitive to selenium deficiency because selenoproteins
      are significant in biosynthesis and activity of thyroid hormones; besides, some
      selenoproteins as glutathione peroxidase are involved in inhibiting apoptosis.
      Thus, selenium malabsorption in CD can be thought as a key factor directly
      leading to thyroid and intestinal damage. Considering the complexity of this
      interaction and on the basis of available evidence, the aim of this review is to
      assess as preventive and therapeutic target the role of IL-15 and selenium in the
      pathogeneses of both CD and AITD.

PMID- 21169671
TI  - The effect of brushing motion on the cyclic fatigue of rotary nickel titanium
      instruments.
AB  - The goal of the study is to evaluate if the use of rotary nickel-titanium (RNT)
      instruments, as Hedstroem files, is safe. Twelve twisted files (TF) RNT
      instruments size 06-25 were selected and randomly divided in 2 groups of 6
      instruments each. Group A (new instruments) were used as control. Group B (test)
      instruments were clinically used only as Hedstroem files in a canal that had been
      previously instrumented to the working length with other 06-25 RNT instruments.
      Group B instruments were used only in the straight portion of the canal (1 minute
      at 1000 rpm). A cyclic fatigue test was performed for each instrument of groups.
      Data were statistically analyzed (Student's t-test). Results showed no
      significant difference (P > 0.05) between groups A and B. Data confirmed that the
      use of TF instruments as Hedstroem files is a safe procedure. Cross section
      images and volumes of the same instrument, before and after cyclic fatigue
      testing, have been obtained by means of microtomographic analysis to evaluate
      possible microstructure alterations.

PMID- 21169672
TI  - An alternative method to record rising temperatures during dental implant site
      preparation: a preliminary study using bovine bone.
AB  - Overheating is constantly mentioned as a risk factor for bone necrosis that could
      compromise the dental implant primary stability. Uncontrolled thermal injury can
      result in a fibrous tissue, interpositioned at the implant-bone interface,
      compromising the long-term prognosis. The methods used to record temperature rise
      include either direct recording by thermocouple instruments or indirect
      estimating by infrared thermography. This preliminary study was carried out using
      bovine bone and a different method of temperatures rising estimation is
      presented. Two different types of drills were tested using fluoroptic thermometer
      and the effectiveness of this alternative temperature recording method was
      evaluated.

PMID- 21169673
TI  - Informed consent in experimentation involving mentally impaired persons: ethical
      issues.
AB  - The problem of experimentation involving subjects whose mental condition prevents
      them from understanding information and providing proper informed consent has
      been addressed in various codes, declarations, conventions, treaties and
      regulations adopted by national, international and supranational institutions and
      authorities. This article summarizes the basic ethical criteria these documents
      provide and stresses the historical development from the nearly total exclusion
      of incapacitated subjects, established in the mid-twentieth century, to their
      contemporary inclusion in clinical trials on certain ethical conditions. The
      problem of proxy consent by legal representatives for participation in clinical
      trials is addressed particularly in reference to current Italian regulations.
      Exceptions to human experimentation requirements in emergency situations are also
      briefly discussed.

PMID- 21169674
TI  - Communication for health promotion: history and identification of effective
      methods.
AB  - This work aims to delineate the long journey of health communication, from the
      beginning to the present, stressing how the concept of health service and human
      health have been evolving together with the kind of political approach to the
      problem. First, the approach was mainly repressive and based on the surveillance
      of territory, so that jurisdiction in health matters was centralized and
      entrusted to the Ministry of Interior. Consequently, communication had little
      space and was directed to an elite group of insiders, who were able to cope with
      any public health emergencies, using a very technical and essential language,
      confusing for most people. In the course of the years, we understood that the
      reaching of the objective health could be realized with the involvement of
      citizens, organized groups, public and private institutions. Therefore, it is
      necessary to ensure citizens the right to receive a clear and correct
      information, enabling them to be self responsible and better manage their health,
      in a more and more personalized way, using an authoritative but confidential
      language and all the modern media.

PMID- 21169675
TI  - The body as a simulacrum of identity: the subjective experience in the eating
      disorders.
AB  - This study aims at better understanding the subjective experience, the so-called
      Erlebnis, in individuals diagnosed with Eating Disorders (ED). We shall highlight
      the particular way in which people with such disorders perceive their own bodies
      and specifically how they perceive their bodies in the presence of other people.
      To this end we shall analyze the subjective experience by means of two concepts
      as described by French philosopher Jean-Paul Sartre: "body-self" and "body
      forothers". Our hypothesis is that some people suffering from eating disorders,
      especially those with a diagnosis of Eating Disorders Not Otherwise Specified
      (EDNOS), experience their body mainly as body-for-others. Rather than a
      diagnostic category, EDNOS could be conceived as an anthropological configuration
      vulnerable to ED. Eating disorders appear as an "identity disorder" characterized
      by a suspension of the experiential polarity between self and other-than-self.

PMID- 21169676
TI  - Arthropod-borne diseases in Italy: from a neglected matter to an emerging health
      problem.
AB  - In medical entomology, "Arthropod Borne Diseases", or "Vector Borne Diseases"
      (VBD) are intended as a group of human and animal infections caused by different
      pathogen organisms (protozoa, helminths, bacteria and viruses) transmitted by the
      bite of a bloodsucking insect or arachnid. It is commonly known that the
      infectious diseases transmitted by Arthropods are mainly affecting tropical and
      subtropical countries, nevertheless some of them were or are still common also in
      the northern hemisphere, where they are usually maintained under control. VBD
      still represent some of the most important public health problems in the endemic
      areas but are becoming source of concern for developed countries too. Since the
      last decades of the past century, a number of VBD has been spreading
      geographically, being recorded for the first time in areas outside their original
      range. This phenomenon is strictly related to the peculiar epidemiological
      characteristics of these diseases, that are considered the most susceptible to
      climatic, environmental and socioeconomic changes. This article is a short
      overview of the VBD endemic and emerging in Italy. The possibility that some
      exotic vectors and/or pathogens could be introduced and become established in
      Italy is also discussed.

PMID- 21169677
TI  - Short-term monitoring of benzene air concentration in an urban area: a
      preliminary study of application of Kruskal-Wallis non-parametric test to assess
      pollutant impact on global environment and indoor.
AB  - In step with the need to develop statistical procedures to manage small-size
      environmental samples, in this work we have used concentration values of benzene
      (C6H6), concurrently detected by seven outdoor and indoor monitoring stations
      over 12 000 minutes, in order to assess the representativeness of collected data
      and the impact of the pollutant on indoor environment. Clearly, the former issue
      is strictly connected to sampling-site geometry, which proves critical to
      correctly retrieving information from analysis of pollutants of sanitary
      interest. Therefore, according to current criteria for network-planning, single
      stations have been interpreted as nodes of a set of adjoining triangles; then, a)
      node pairs have been taken into account in order to estimate pollutant
      stationarity on triangle sides, as well as b) node triplets, to statistically
      associate data from air-monitoring with the corresponding territory area, and c)
      node sextuplets, to assess the impact probability of the outdoor pollutant on
      indoor environment for each area. Distributions from the various node
      combinations are all non-Gaussian, in the consequently, Kruskal-Wallis (KW) non
      parametric statistics has been exploited to test variability on continuous
      density function from each pair, triplet and sextuplet. Results from the above
      mentioned statistical analysis have shown randomness of site selection, which has
      not allowed a reliable generalization of monitoring data to the entire selected
      territory, except for a single "forced" case (70%); most important, they suggest
      a possible procedure to optimize network design.

PMID- 21169678
TI  - Emerging concepts in high-impact publishing: insights from the First Brazilian
      Colloquium on High Impact Research and Publishing.
AB  - Reports of scientific research are published by selective journals only when they
      meet stringent criteria, first and foremost of which are the quality and
      importance of the research. Even when the research is excellent, other elements
      come into play to determine if the manuscript will be accepted for publication.
      Many of these factors are under direct control of the researcher-author, but not
      all authors are aware of the elements of high-impact scientific writing. At the
      First Brazilian Colloquium on High Impact Research and Publishing, editors of
      leading biomedical journals provided insight on the aspects of scientific
      reporting that favor acceptance (or immediate rejection). This commentary
      summarizes the editors' advice and uses the debate that followed as the basis for
      analyzing emerging concepts in high-impact publishing. Lessons learned from this
      meeting are relevant to researcher-authors in other non-anglophone countries as
      well as to their educators and administrators who wish to improve the impact of
      the research that they support and finance.

PMID- 21169679
TI  - Diffraction structural biology--introductory overview.
AB  - An introductory overview to the special issue papers on diffraction structural
      biology in this issue of the journal.

PMID- 21169680
TI  - Three-dimensional structural analysis of eukaryotic flagella/cilia by electron
      cryo-tomography.
AB  - Electron cryo-tomography is a potential approach to analyzing the three
      dimensional conformation of frozen hydrated biological macromolecules using
      electron microscopy. Since projections of each individual object illuminated from
      different orientations are merged, electron tomography is capable of structural
      analysis of such heterogeneous environments as in vivo or with polymorphism,
      although radiation damage and the missing wedge are severe problems. Here, recent
      results on the structure of eukaryotic flagella, which is an ATP-driven bending
      organelle, from green algae Chlamydomonas are presented. Tomographic analysis
      reveals asymmetric molecular arrangements, especially that of the dynein motor
      proteins, in flagella, giving insight into the mechanism of planar asymmetric
      bending motion. Methodological challenges to obtaining higher-resolution
      structures from this technique are also discussed.

PMID- 21169681
TI  - Crystal structure of stable protein CutA1 from psychrotrophic bacterium
      Shewanella sp. SIB1.
AB  - CutA1 is widely found in bacteria, plants and animals, including humans. The
      functions of CutA1, however, have not been well clarified. It is known that
      CutA1s from Pyrococcus horikoshii, Thermus thermophilus and Oryza sativa unfold
      at temperatures remarkably higher than the growth temperatures of the host
      organisms. In this work the crystal structure of CutA1 from the psychrotrophic
      bacterium Shewanella sp. SIB1 (SIB1-CutA1) in a trimeric form was determined at
      2.7 A resolution. This is the first crystal structure of a psychrotrophic CutA1.
      The overall structure of SIB1-CutA1 is similar to those of CutA1 from Homo
      sapiens, Escherichia coli, Pyrococcus horikoshii, Thermus thermophilus, Termotoga
      maritima, Oryza sativa and Rattus norvergicus. A peculiarity is observed in the
      beta2 strand. The beta2 strand is divided into two short beta strands, beta2a and
      beta2b, in SIB1-CutA1. A thermal denaturation experiment revealed that SIB1-CutA1
      does not unfold completely at 363 K at pH 7.0, although Shewanella sp. SIB1
      cannot grow at temperatures exceeding 303 K. These results indicate that the
      trimeric structural motif of CutA1 is the critical factor in its unusually high
      stability and suggest that CutA1 needs to maintain its high stability in order to
      function, even in psychrotrophs.

PMID- 21169682
TI  - UV LED lighting for automated crystal centring.
AB  - A direct outcome of the exponential growth of macromolecular crystallography is
      the continuously increasing demand for synchrotron beam time, both from academic
      and industrial users. As more and more projects entail screening a profusion of
      sample crystals, fully automated procedures at every level of the experiments are
      being implemented at all synchrotron facilities. One of the major obstacles to
      achieving such automation lies in the sample recognition and centring in the X
      ray beam. The capacity of UV light to specifically react with aromatic residues
      present in proteins or with DNA base pairs is at the basis of UV-assisted crystal
      centring. Although very efficient, a well known side effect of illuminating
      biological samples with strong UV sources is the damage induced on the irradiated
      samples. In the present study the effectiveness of a softer UV light for crystal
      centring by taking advantage of low-power light-emitting diode (LED) sources has
      been investigated. The use of UV LEDs represents a low-cost solution for crystal
      centring with high specificity.

PMID- 21169683
TI  - Approach for growth of high-quality and large protein crystals.
AB  - Three crystallization methods for growing large high-quality protein crystals,
      i.e. crystallization in the presence of a semi-solid agarose gel, top-seeded
      solution growth (TSSG) and a large-scale hanging-drop method, have previously
      been presented. In this study the effectiveness of crystallization in the
      presence of a semi-solid agarose gel has been further evaluated by crystallizing
      additional proteins in the presence of 2.0% (w/v) agarose gel, resulting in
      complete gelification with high mechanical strength. In TSSG the seed crystals
      are hung by a seed holder protruding from the top of the growth vessel to prevent
      polycrystallization. In the large-scale hanging-drop method, a cut pipette tip
      was used to maintain large-scale droplets consisting of protein-precipitant
      solution. Here a novel crystallization method that combines TSSG and the large
      scale hanging-drop method is reported. A large and single crystal of lysozyme was
      obtained by this method.

PMID- 21169684
TI  - The alternating access mechanism of transport as observed in the sodium-hydantoin
      transporter Mhp1.
AB  - Secondary active transporters move molecules across cell membranes by coupling
      this process to the energetically favourable downhill movement of ions or protons
      along an electrochemical gradient. They function by the alternating access model
      of transport in which, through conformational changes, the substrate binding site
      alternately faces either side of the membrane. Owing to the difficulties in
      obtaining the crystal structure of a single transporter in different
      conformational states, relatively little structural information is known to
      explain how this process occurs. Here, the structure of the sodium
      benzylhydantoin transporter, Mhp1, from Microbacterium liquefaciens, has been
      determined in three conformational states; from this a mechanism is proposed for
      switching from the outward-facing open conformation through an occluded structure
      to the inward-facing open state.

PMID- 21169685
TI  - Crystallization and preliminary structural analysis of the giant haemoglobin from
      Glossoscolex paulistus at 3.2 A.
AB  - Glossoscolex paulistus is a free-living earthworm encountered in south-east
      Brazil. Its oxygen transport requirements are undertaken by a giant extracellular
      haemoglobin, or erythrocruorin (HbGp), which has an approximate molecular mass of
      3.6 MDa and, by analogy with its homologue from Lumbricus terrestris (HbLt), is
      believed to be composed of a total of 180 polypeptide chains. In the present work
      the full 3.6 MDa particle in its cyanomet state was purified and crystallized
      using sodium citrate or PEG8000 as precipitant. The crystals contain one-quarter
      of the full particle in the asymmetric unit of the I222 cell and have parameters
      of a = 270.8 A, b = 320.3 A and c = 332.4 A. Diffraction data were collected to
      3.15 A using synchrotron radiation on beamline X29A at the Brookhaven National
      Laboratory and represent the highest resolution data described to date for
      similar erythrocruorins. The structure was solved by molecular replacement using
      a search model corresponding to one-twelfth of its homologue from HbLt. This
      revealed that HbGp belongs to the type I class of erythrocruorins and provided an
      interpretable initial electron density map in which many features including the
      haem groups and disulfide bonds could be identified.

PMID- 21169686
TI  - Structure analysis of group I plant nucleases.
AB  - Anticancer drugs attacking nucleic acids of the target cells have so far been
      based on animal or fungal ribonucleases. Plant nucleases have been proved to
      exhibit decreased cytotoxic side effects. Tomato bifunctional nuclease 1 with
      activity against both single-stranded and double-stranded RNA and DNA was
      produced in tobacco leaves as recombinant protein. The enzyme crystallizes under
      several different crystallization conditions. The presence of Zn(2+) ions was
      confirmed by X-ray fluorescence. First crystallographic data were obtained.

PMID- 21169687
TI  - A new paradigm for macromolecular crystallography beamlines derived from high
      pressure methodology and results.
AB  - Biological structures can now be investigated at high resolution by high-pressure
      X-ray macromolecular crystallography (HPMX). The number of HPMX studies is
      growing, with applications to polynucleotides, monomeric and multimeric proteins,
      complex assemblies and even a virus capsid. Investigations of the effects of
      pressure perturbation have encompassed elastic compression of the native state,
      study of proteins from extremophiles and trapping of higher-energy conformers
      that are often of biological interest; measurements of the compressibility of
      crystals and macromolecules were also performed. HPMX results were an incentive
      to investigate short and ultra-short wavelengths for standard biocrystallography.
      On cryocooled lysozyme crystals it was found that the data collection efficiency
      using 33 keV photons is increased with respect to 18 keV photons. This conclusion
      was extended from 33 keV down to 6.5 keV by exploiting previously published data.
      To be fully exploited, the potential of higher-energy photons requires detectors
      with a good efficiency. Accordingly, a new paradigm for MX beamlines was
      suggested, using conventional short and ultra-short wavelengths, aiming at the
      collection of very high accuracy data on crystals under standard conditions or
      under high pressure. The main elements of such beamlines are outlined.

PMID- 21169688
TI  - Single-crystal Raman spectroscopy and X-ray crystallography at beamline X26-C of
      the NSLS.
AB  - Three-dimensional structures derived from X-ray diffraction of protein crystals
      provide a wealth of information. Features and interactions important for the
      function of macromolecules can be deduced and catalytic mechanisms postulated.
      Still, many questions can remain, for example regarding metal oxidation states
      and the interpretation of 'mystery density', i.e. ambiguous or unknown features
      within the electron density maps, especially at ~2 A resolutions typical of most
      macromolecular structures. Beamline X26-C at the National Synchrotron Light
      Source (NSLS), Brookhaven National Laboratory (BNL), provides researchers with
      the opportunity to not only determine the atomic structure of their samples but
      also to explore the electronic and vibrational characteristics of the sample
      before, during and after X-ray diffraction data collection. When samples are
      maintained under cryo-conditions, an opportunity to promote and follow
      photochemical reactions in situ as a function of X-ray exposure is also provided.
      Plans are in place to further expand the capabilities at beamline X26-C and to
      develop beamlines at NSLS-II, currently under construction at BNL, which will
      provide users access to a wide array of complementary spectroscopic methods in
      addition to high-quality X-ray diffraction data.

PMID- 21169689
TI  - Biomolecular solution X-ray scattering at the National Synchrotron Light Source.
AB  - In recent years there has been a growing interest in the application of X-ray
      scattering techniques to biomolecules in solution. At NSLS, a new undulator-based
      beamline, X9, has been constructed to address the oversubscribed user demand for
      X-ray scattering. Beamline X9 has the capability to perform small/wide-angle X
      ray scattering (SAXS/WAXS) all in one single instrument. This is accomplished by
      utilizing a vacuum sample/detector chamber that is an integral part of the SAXS
      scattering flight path. This vacuum chamber allows a WAXS detector to be
      positioned at a close distance from the sample, while not interfering with
      scattered X-rays at small angles from reaching the SAXS detector. A regular
      training program, the X9 workbench, has also been established to allow users to
      become familiar with beamline X9 for solution X-ray scattering.

PMID- 21169690
TI  - Structural insights and ab initio sequencing within the DING proteins family.
AB  - DING proteins constitute an intriguing family of phosphate-binding proteins that
      was identified in a wide range of organisms, from prokaryotes and archae to
      eukaryotes. Despite their seemingly ubiquitous occurrence in eukaryotes, their
      encoding genes are missing from sequenced genomes. Such a lack has considerably
      hampered functional studies. In humans, these proteins have been related to
      several diseases, like atherosclerosis, kidney stones, inflammation processes and
      HIV inhibition. The human phosphate binding protein is a human representative of
      the DING family that was serendipitously discovered from human plasma. An
      original approach was developed to determine ab initio the complete and exact
      sequence of this 38 kDa protein by utilizing mass spectrometry and X-ray data in
      tandem. Taking advantage of this first complete eukaryotic DING sequence, a
      immunohistochemistry study was undertaken to check the presence of DING proteins
      in various mice tissues, revealing that these proteins are widely expressed.
      Finally, the structure of a bacterial representative from Pseudomonas fluorescens
      was solved at sub-angstrom resolution, allowing the molecular mechanism of the
      phosphate binding in these high-affinity proteins to be elucidated.

PMID- 21169691
TI  - Protein surface shielding agents in protein crystallization.
AB  - The molecules adhering temporarily on the surface of protein molecules change the
      propensity of protein molecules to deposit on the crystal surface in a definite
      position and orientation. The concepts of competitive adhesion modes and protein
      surface shielding agents acting on the surface of molecules in a non-equilibrium
      process of protein crystallization provide a useful platform for the control of
      crystallization. The desirable goal, i.e. a transient preference of a single
      dominating adhesion mode between protein molecules during crystallization, leads
      to uniform deposition of proteins in a crystal. This condition is the most
      important factor for diffraction quality and thus also for the accuracy of
      protein structure determination. The presented hypothesis is a generalization of
      the experimentally well proven behaviour of hydrophilic polymers on the surface
      of protein molecules of other compounds.

PMID- 21169692
TI  - Research and development of an electron beam focusing system for a high
      brightness X-ray generator.
AB  - A new type of rotating anticathode X-ray generator, where an electron beam of up
      to 60 keV irradiates the inner surface of a U-shaped Cu anticathode, has achieved
      a beam brilliance of 130 kW mm(-2) (at 2.3 kW). A higher-flux electron beam is
      expected from simulation by optimizing the geometry of a combined-function-type
      magnet instead of the fringing field of the bending magnet. In order to minimize
      the size of the X-ray source the electron beam has been focused over a short
      distance by a new combined-function bending magnet, whose geometrical shape was
      determined by simulation using the Opera-3D, General Particle Tracer and CST
      STUDIO codes. The result of the simulation clearly shows that the role of
      combined functions in both the bending and the steering magnets is important for
      focusing the beam to a small size. FWHM sizes of the beam are predicted by
      simulation to be 0.45 mm (horizontal) and 0.05 mm (vertical) for a 120 keV/75 mA
      beam, of which the effective brilliance is about 500 kW mm(-2) on the supposition
      of a two-dimensional Gaussian distribution. High-power tests have begun using a
      high-voltage 120 kV/75 mA power supply for the X-ray generator instead of 60
      kV/100 mA. The beam focus size on the target will be verified in the experiments.

PMID- 21169693
TI  - Detection of the reaction intermediates catalyzed by a copper amine oxidase.
AB  - To reveal the chemical changes and geometry changes of active-site residues that
      cooperate with a reaction is important for understanding the functional mechanism
      of proteins. Consecutive temporal analyses of enzyme structures have been
      performed during reactions to clarify structure-based reaction mechanisms.
      Phenylethylamine oxidase from Arthrobacter globiformis (AGAO) contains a copper
      ion and topaquinone (TPQ(ox)). The catalytic reaction of AGAO catalyzes oxidative
      deaminations of phenylethylamine and consists of reductive and oxidative half
      reactions. In the reduction step, TPQ(ox) reacts with a phenylethylamine (PEA)
      substrate giving rise to a topasemiquinone (TPQ(sq)) formed Schiff-base and
      produces phenylacetaldehyde. To elucidate the mechanism of the reductive half
      reaction, an attempt was made to trap the reaction intermediates in order to
      analyze their structures. The reaction proceeded within the crystals when AGAO
      crystals were soaked in a PEA solution and freeze-trapped in liquid nitrogen. The
      reaction stage of each crystal was confirmed by single-crystal microspectrometry,
      before X-ray diffraction measurements were made of four reaction intermediates.
      The structure at 15 min after the onset of the reaction was analyzed at atomic
      resolution, and it was shown that TPQ(ox) and some residues in the substrate
      channel were alternated via catalytic reductive half-reactions.

PMID- 21169694
TI  - Purine nucleoside phosphorylase from Schistosoma mansoni in complex with ribose-1
      phosphate.
AB  - Schistosomes are blood flukes which cause schistosomiasis, a disease affecting
      approximately 200 million people worldwide. Along with several other important
      human parasites including trypanosomes and Plasmodium, schistosomes lack the de
      novo pathway for purine synthesis and depend exclusively on the salvage pathway
      for their purine requirements, making the latter an attractive target for drug
      development. Part of the pathway involves the conversion of inosine (or
      guanosine) into hypoxanthine (or guanine) together with ribose-1-phosphate (R1P)
      or vice versa. This inter-conversion is undertaken by the enzyme purine
      nucleoside phosphorylase (PNP) which has been used as the basis for the
      development of novel anti-malarials, conceptually validating this approach. It
      has been suggested that, during the reverse reaction, R1P binding to the enzyme
      would occur only as a consequence of conformational changes induced by
      hypoxanthine, thus making a binary PNP-R1P complex unlikely. Contradictory to
      this statement, a crystal structure of just such a binary complex involving the
      Schistosoma mansoni enzyme has been successfully obtained. The ligand shows an
      intricate hydrogen-bonding network in the phosphate and ribose binding sites and
      adds a further chapter to our knowledge which could be of value in the future
      development of selective inhibitors.

PMID- 21169695
TI  - Structure of the inhibitor complex of old yellow enzyme from Trypanosoma cruzi.
AB  - Old yellow enzyme (OYE) is an NADPH oxidoreductase which contains flavin
      mononucleotide as prosthetic group. The X-ray structures of OYE from Trypanosoma
      cruzi (TcOYE) which produces prostaglandin (PG) F(2alpha) from PGH(2) have been
      determined in the presence or absence of menadione. The binding motif of
      menadione, known as one of the inhibitors for TcOYE, should accelerate the
      structure-based development of novel anti-chagasic drugs that inhibit PGF(2alpha)
      production specifically.

PMID- 21169696
TI  - Microcrystallography, high-pressure cryocooling and BioSAXS at MacCHESS.
AB  - The Macromolecular Diffraction Facility at the Cornell High Energy Synchrotron
      Source (MacCHESS) is a national research resource supported by the National
      Center for Research Resources of the US National Institutes of Health. MacCHESS
      is pursuing several research initiatives designed to benefit both CHESS users and
      the wider structural biology community. Three initiatives are presented in
      further detail: microcrystallography, which aims to improve the collection of
      diffraction data from crystals a few micrometers across, or small well
      diffracting regions of inhomogeneous crystals, so as to obtain high-resolution
      structures; pressure cryocooling, which can stabilize transient structures and
      reduce lattice damage during the cooling process; and BioSAXS (small-angle X-ray
      scattering on biological solutions), which can extract molecular shape and other
      structural information from macromolecules in solution.

PMID- 21169697
TI  - Using lanthanoid complexes to phase large macromolecular assemblies.
AB  - Lanthanoid ions exhibit extremely large anomalous X-ray scattering at their
      L(III) absorption edge. They are thus well suited for anomalous diffraction
      experiments. A novel class of lanthanoid complexes has been developed that
      combines the physical properties of lanthanoid atoms with functional chemical
      groups that allow non-covalent binding to proteins. Two structures of large
      multimeric proteins have already been determined by using such complexes. Here
      the use of the luminescent europium tris-dipicolinate complex [Eu(DPA)(3)](3-) to
      solve the low-resolution structure of a 444 kDa homododecameric aminopeptidase,
      called PhTET1-12s from the archaea Pyrococcus horikoshii, is reported.
      Surprisingly, considering the low resolution of the data, the experimental
      electron density map is very well defined. Experimental phases obtained by using
      the lanthanoid complex lead to maps displaying particular structural features
      usually observed in higher-resolution maps. Such complexes open a new way for
      solving the structure of large molecular assemblies, even with low-resolution
      data.

PMID- 21169698
TI  - Deriving the ultrastructure of alpha-crustacyanin using lower-resolution
      structural and biophysical methods.
AB  - The low-resolution structure of alpha-crustacyanin has been determined to 30 A
      resolution using negative-stain electron microscopy (EM) with single-particle
      averaging. The protein, which is an assembly of eight beta-crustacyanin dimers,
      appears asymmetrical and rather open in layout. A model was built to the EM map
      using the X-ray crystallographic structure of beta-crustacyanin guided by PISA
      interface analyses. The model has a theoretical sedimentation coefficient that
      matches well with the experimentally derived value from sedimentation velocity
      analytical ultracentrifugation. Additionally, the EM model has similarities to
      models calculated independently by rigid-body modelling to small-angle X-ray
      scattering (SAXS) data and extracted in silico from the beta-crustacyanin crystal
      lattice. Theoretical X-ray scattering from each of these models is in reasonable
      agreement with the experimental SAXS data and together suggest an overall design
      for the alpha-crustacyanin assembly.

PMID- 21169699
TI  - Optimization of salt concentration in PEG-based crystallization solutions.
AB  - Although polyethylene glycol (PEG) is the most widely used precipitant in protein
      crystallization, the concentration of co-existing salt in the solution has not
      been well discussed. To determine the optimum salt concentration range, several
      kinds of protein were crystallized in a 30% PEG 4000 solution at various NaCl
      concentrations with various pH levels. It was found that, if crystallization
      occurred, the lowest effective salt concentration depended on the pH of the
      protein solution and the pI of the protein molecule; that is, higher salt
      concentrations were required for crystal growth if the difference between pH and
      pI was increasing. The linear relationship between the charge density of the
      protein and the ionic strength of the crystallization solution was further
      verified. These results suggested that the lowest effective concentration of salt
      in a crystallization solution can be predicted before performing a
      crystallization experiment. Our results can be a tip for tuning crystallization
      conditions by the vapor-diffusion method.

PMID- 21169700
TI  - Improvement in the quality of hematopoietic prostaglandin D synthase crystals in
      a microgravity environment.
AB  - Human hematopoietic prostaglandin synthase, one of the better therapeutic target
      enzymes for allergy and inflammation, was crystallized with 22 inhibitors and in
      three inhibitor-free conditions in microgravity. Most of the space-grown crystals
      showed better X-ray diffraction patterns than the terrestrially grown ones,
      indicating the advantage of a microgravity environment on protein
      crystallization, especially in the case of this protein.

PMID- 21169703
TI  - Harnessing the power of partnership and community collaboration: addressing youth
      health inequalities.

PMID- 21169704
TI  - Walk together children with no wasted steps: community-academic partnering for
      equal power in NIH proposal development.
AB  - BACKGROUND: Community-based participatory research (CBPR) approaches equitably
      involve community members and researchers throughout the research process. A
      developing literature examines problems in CBPR partnerships, but less is written
      about community groups using CBPR to access university resources to address
      community-prioritized health concerns. OBJECTIVE: We sought to examine issues in
      two stages of a National Institutes of Health (NIH)-funded CBPR partnership: (1)
      joint proposal preparation, and (2) grant administration. METHODS: We used a case
      study approach to analyze data (partner dialogs, meeting notes, interviews, and
      press coverage) from a longstanding community-academic partnership. RESULTS: The
      partnership received NIH Partners in Research Program funding. During joint
      proposal preparation, issues included (1) learning to practice operating
      principles, such as "talking in ways that all people can understand," (2)
      streamlining proposal design to facilitate communication with community members,
      and (3) addressing inequities inherent in community-academic budget sharing.
      During the administration phase, issues included (1) community partner struggles
      with administrative requirements, (2) inequities in indirect cost (IDC)
      allocations, and (3) the impact of a natural disaster. CONCLUSION: Separately
      funded CBPR grants can contribute to community partner development, but make
      substantive demands on small, grassroots community organizations. Funders should
      consider taking more responsibility in developing community resources and
      infrastructure to ensure that grassroots community groups have the power to be
      equal partners. More accurate accounting of costs and benefits of CBPR to
      vulnerable communities should be in place to ensure communities receive adequate
      return on the time they invest in partnering with universities.

PMID- 21169705
TI  - Improving dietary and physical activity practices in group homes serving
      residents with severe mental illness.
AB  - BACKGROUND: People with severe mental illness (SMI) are at least 50% more likely
      to be overweight for various reasons, including poor nutrition, sedentary
      lifestyles, and side effects of antipsychotic medications. OBJECTIVES: Among
      residents with SMI who live in group homes, we examined (1) factors that affected
      the motivations of both group home operators and residents around improvement of
      residents' diet and physical activity, (2) how operators and residents viewed
      responsibility for maintaining good health in group homes, and (3) strategies
      from operators and residents for improving diet and exercise. METHODS: The
      research team conducted 6 focus groups-3 with group home operators and 3 with
      residents, using a community-based participatory research (CBPR) process and
      qualitative data analysis. RESULTS: Both group home operators and residents
      discussed conflicting feelings about foods they know as healthy and foods they
      prefer to eat. Operators attributed barriers to better health to the perceived
      negative attitudes of residents and providers, lack of communication with health
      care providers, and poor working relationships with the state licensing body that
      protects individual rights on lifestyle choices. Residents reported barriers of
      their own negative attitudes, limited menu options, lack of organized activities,
      existing health problems, and side effects of medications. CONCLUSION: Residents
      and operators had concrete suggestions for changes they could make individually,
      as well as recommendations for systemic changes to support healthier lifestyles.
      These recommendations provide a basis for designing an urgently needed pilot
      intervention program to address the current epidemic of obesity and diabetes in
      people with SMI residing in group homes.

PMID- 21169706
TI  - Influences on tobacco use among urban Hispanic young adults in Baltimore:
      findings from a qualitative study.
AB  - BACKGROUND: Among Hispanics, lung cancer is the leading cause of cancer-related
      death for men and the second leading cause of cancer death for women in the
      United States. Despite recent growth in Baltimore City's Hispanic population, few
      data exist on tobacco use behaviors in this group. OBJECTIVES: The present
      research sought to explore the social and environmental influences and norms that
      encourage or discourage tobacco use among Hispanic young adults in Baltimore.
      METHODS: In collaboration with several community stakeholders, we conducted focus
      groups with Hispanic young adults 18 to 24 years old. Participants were recruited
      from a community-based service organization and invited to take part in one of
      four focus groups segregated by gender. RESULTS: A total of 13 young men and 11
      young women participated. Data from these focus groups indicate that cultural
      identity and gender norms leverage substantial influence in young adults'
      decision about whether, where, and with whom to smoke. The data also suggest
      multiple social and familial influences on their smoking and nonsmoking
      behaviors. Participants identified smoking practices and clear brand preferences
      that they feel distinguish Hispanics from other racial and ethnic groups. Despite
      acknowledging the high price of cigarettes, cost was not mentioned as a factor
      influential in their smoking decisions. CONCLUSION: These results provide
      essential guidance for the development of appropriate tobacco prevention and
      cessation intervention strategies and policy recommendations to eliminate tobacco
      use among Hispanic young adults in Baltimore.

PMID- 21169707
TI  - Developing research and recruitment while fostering stakeholder engagement in a
      National Institutes of Mental Health-funded Interventions and Practice Research
      Infrastructure Programs grant for depression.
AB  - BACKGROUND: In the context of a National Institutes of Mental Health-funded
      Interventions and Practice Research Infrastructure Programs (IP-RISP) grant for
      the treatment of depression, a partnership was developed between a community
      mental health organization and a team of researchers. OBJECTIVES: This paper
      describes the collaborative process, key challenges, and strategies employed to
      meet the goals of the first phase of the grant, which included development of a
      working and sustainable partnership and building capacity for recruitment and
      research. METHODS: This paper was developed through the use of qualitative
      interviews and discussion with a variety of IP-RISP partners. LESSONS LEARNED:
      Communication with multiple stakeholders through varied channels, feedback from
      stakeholders on research procedures, and employing a research liaison at the
      clinic have been key strategies in the first phase of the grant. CONCLUSION: The
      strategies we employed allowed multiple stakeholders to contribute to the larger
      mission of the IP-RISP and helped to establish an ongoing research program within
      the mental health organization.

PMID- 21169708
TI  - Lessons learned from a community-academic partnership addressing adolescent
      pregnancy prevention in Filipino American families.
AB  - BACKGROUND: Filipino Americans have more adolescent pregnancies than other Asian
      Pacific Islanders (APIs). Few community-academic collaborations have addressed
      adolescent pregnancy prevention in this community. OBJECTIVES: We sought to
      describe the lessons learned from and impact of a community-based teen pregnancy
      prevention program for Filipino Americans implemented by a Filipina pediatrics
      resident. METHODS: We formed a community-academic partnership between the
      Filipino Youth Coalition, a community-based organization (CBO) in San Jose,
      California, and the Stanford School of Medicine's Pediatric Advocacy Program. We
      developed a culturally tailored parent-teen conference addressing adolescent
      pregnancy prevention in Filipino Americans. We qualitatively and quantitatively
      evaluated this intervention by collecting both pre- and post-conference data
      using a convenience sample design. LESSONS LEARNED: Engaging particular aspects
      of Filipino culture (i.e., religion and intergenerational differences) helped to
      make this community-academic partnership successful. For physicians-in-training
      who are conducting community-based participatory research (CBPR), project
      challenges may include difficulties in building and maintaining academic-
      community relationships, struggles to promote sustainability, and conflicting
      goals of "community insiders" and "academic outsiders." Authors offer insights
      and implications for residents interested in practicing CBPR. CONCLUSION: CBPR is
      a key tool for exploring health issues in understudied populations. CBPR
      experiences can provide meaningful educational opportunities for physicians-in
      training and can build sustained capacity in CBOs. They can also help residents
      to develop analytic skills, directly affect the health of the communities they
      serve, and, for minority physicians, give back to the communities they call home.

PMID- 21169709
TI  - The development of a community-based family asthma management intervention for
      Puerto Rican children.
AB  - BACKGROUND: Puerto Rican children maintain disproportionately high asthma
      prevalence rates and effective asthma management interventions are needed.
      OBJECTIVES: This article describes how community-based participatory research
      (CBPR) was implemented in the development of a culturally tailored family asthma
      management intervention for Puerto Rican children: CALMA (a Spanish acronym for
      Take Control, Empower Yourself, and Achieve Asthma Management). METHOD: CALMA was
      developed according to CBPR principles and contemporary asthma guidelines through
      the collaboration of diverse members of the local, professional, and medical
      communities, academia, and local government. All group members contributed unique
      perspectives, making CALMA's development a collaborative effort. LESSONS LEARNED:
      The CALMA community dealt with challenges in both incorporating and managing a
      diverse group of stakeholders and maintaining equity in decision making power.
      However, the community maintained strengths, such as incorporating culturally
      accepted remedies and addressing culturally specific myths in the intervention,
      as well as having the medical community directly involved in overseeing the
      accuracy of the intervention. CONCLUSION: A CBPR approach enhanced the cultural
      sensitivity of the intervention as well as its potential for sustainability.

PMID- 21169710
TI  - Community-based participatory research in a large cohort study of chronic
      diseases among Alaska native adults.
AB  - BACKGROUND: In 2001, the National Cancer Institute (NCI) funded a project to
      develop methods to recruit American Indian and Alaska Native (AI/AN) adults for a
      prospective cohort study of chronic disease risk and protective factors.
      OBJECTIVE: We describe how the use of community-based participatory research
      (CBPR) principles led to more effective study design and implementation in a
      study in Alaska. METHODS: CBPR elements included collaboration between
      researchers and tribes at all stages of the project, capacity building through
      training AI/AN staff in research methods, and knowledge dissemination through
      presentations, newsletters, and individual and community health feedback based on
      results of the study. RESULTS: Between March 2004 and August 2006, 3,821 AI/ AN
      adults from 26 Alaskan communities enrolled in the study. Retention in the study
      is high, with over 88% of participants successfully completing a 2-year follow-up
      questionnaire. CONCLUSION: CBPR methods have facilitated effective development of
      study methods, recruitment and retention. Efforts are on-going to continue work
      with this unique AI/AN research participant community.

PMID- 21169711
TI  - Using an alliance of independent health consumer assistance centers to change
      public policy in California.
AB  - PROBLEM: The complexity of the U.S. health care system has created many obstacles
      for individuals and families trying to gain access to health insurance and health
      care services. With a multitude of payers and provider organizations, health
      consumers must navigate complex arrangements that vary by payer, community, and
      employer. PURPOSE: This report describes the Health Consumer Alliance (HCA), an
      innovative collaboration of legal service organizations in California that
      combines individual assistance with broad advocacy work. Specifically, this paper
      highlights HCA's role in addressing systemic health care access issues that
      underlie many of the problems that health consumers face. KEY POINTS: In a 5-year
      period, the HCA assisted more than 60,000 individuals with problems related to
      obtaining access to care and health insurance coverage. The HCA used the
      information gained from this individual assistance to address both local and
      statewide policy issues by pooling the technical and political resources of
      individual health consumer centers (HCC) and their partners. CONCLUSION: The HCA
      has improved access to health care for many individuals beyond its client base by
      protecting indigent health services, expanding eligibility for public programs,
      and preserving the safety net for California's low-income population. The HCA
      model can be example of how information from individual consumer problems can be
      addressed at a broader level to reach and impact systemic change.

PMID- 21169714
TI  - November 2010 Abstracts.
AB  - A selection of important abstracts of articles published in other journals. J
      Orthop Sports Phys Ther 2010;40(11):763-769.

PMID- 21169713
TI  - Lessons learned from undertaking community-based participatory research
      dissertations: the trials and triumphs of two junior health scholars.
AB  - BACKGROUND: For graduate students addressing health issues pertinent to
      marginalized communities, community-based participatory research (CBPR) methods
      may be an appropriate mode of inquiry. Although there are a number of useful
      guides on conducting traditional doctoral dissertations (TDD), there is a paucity
      of similar resources for students engaged in CBPR. OBJECTIVES: Drawing on our own
      experiences, we aimed to describe the key lessons learned from doing
      participatory doctoral research. Furthermore, this paper outlines 6 suggestions
      for those who may be considering or already conducting a CBPR dissertation.
      Suggestions are derived from elements of the CBPR process that were employed in
      our own projects. LESSONS LEARNED: Upon reflection on our experiences conducting
      CBPR dissertations, we identified 4 lessons learned: (1) to understand the
      differences between TDDs and the CBPR approach; (2) to be aware of and able to
      clearly articulate the advantages of CBPR doctoral dissertations; (3) to
      acknowledge and plan for the possible challenges of CBPR doctoral research; and
      (4) to recognize aspects of the CBPR process that contribute to the successful
      completion of doctoral projects. CONCLUSION: This paper provides an additional
      resource for doctoral students, based on our own experiences working on CBPR
      projects. Despite many of the obstacles and challenges, we found the process of
      engaging in CBPR dissertations deeply rewarding, and hope that our experiences
      are useful to others.

PMID- 21169715
TI  - Reliability and relationship between 2 measurements of transversus abdominis
      dimension taken during an abdominal drawing-in maneuver using a novel approach of
      ultrasound imaging.
AB  - STUDY DESIGN: Reliability study of clinical measurement. OBJECTIVES: The primary
      purpose was to develop a reliable method for measuring muscle length changes of
      the transversus abdominis (TrA) during contraction. The secondary purpose was to
      investigate the relationship between changes in thickness and length (as
      indicated by the lateral sliding of the anterior muscle-fascia junction) of the
      TrA muscle during an abdominal drawing-in maneuver. We also provide data on
      between-day reliability of change in thickness (DeltaT) of the TrA. BACKGROUND:
      Ultrasound imaging measurements of TrA thickness at rest (Thr) and during maximal
      contraction (Thm) have been shown to be reliable. However, limited data exist on
      quantifying changes in TrA length (as indicated by the lateral sliding of the
      muscle-fascia junction [Deltax]) and DeltaT during contraction. METHODS: Eighteen
      healthy adults (mean +/- SD age, 22.6 +/- 2.5 years) participated in this study.
      Brightness mode ultrasound images of the TrA were collected at rest and during an
      abdominal drawing-in maneuver. Subjects were examined by the same examiner twice
      within a 48-hour period. DeltaT, DeltaT/Thr, Thr, Thm, and Deltax of the TrA were
      calculated. Medial-lateral movement of the transducer during measurement was
      corrected through a custom-written program that used an internal marker created
      by an echo-absorptive thread attached to the skin. Intraclass correlation
      coefficients (ICC3,1), within-subject coefficient of variance, and standard error
      of measurement were calculated. The relationship between DeltaT and adjusted
      Deltax of the TrA muscle was investigated. RESULTS: The ICC values for Thr, Thm,
      and DeltaT of the TrA muscle were greater than 0.75, with the exception of the
      left DeltaT (0.62) and left DeltaT/Thr (0.49). After adjusting for medial-lateral
      motion of the transducer, the ICC values of adjusted Deltax were above 0.75, and
      the within-subject coefficient of variance was below 10%. There was no
      significant correlation between DeltaT and adjusted Deltax of the TrA.
      CONCLUSION: Ultrasound imaging measurements of TrA thickness and length change
      were shown to be reliable using a novel method to control for medial-lateral
      transducer motion. Measuring different but unrelated dimensional changes in the
      TrA might provide further insight as to the function of the TrA.

PMID- 21169716
TI  - Six weeks of balance training improves sensorimotor function in individuals with
      chronic ankle instability.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVE: To assess the effect of 6
      weeks of balance training on sensorimotor measures previously found to be
      deficient in participants with chronic ankle instability (CAI). BACKGROUND: CAI
      is the tendency toward repeated ankle sprains and recurring symptoms, occurring
      in 40% to 70% of individuals who have previously sustained a lateral ankle
      sprain. Recent studies have found deficits in sensorimotor measures in
      individuals with CAI. As balance training is a common component of ankle
      rehabilitation, understanding its effect on the sensorimotorsystem in individuals
      with CAI may enable us to optimize protocols to better utilize this
      rehabilitation method. METHODS: Twelve participants with CAI and 9 healthy
      volunteers participated. Independent variables were group (CAI, control) and time
      (pretraining, posttraining). Participants with CAI who completed a 6-week balance
      training program and healthy controls who did not get any training were pretested
      and posttested at the beginning and at the end of 6 weeks. RESULTS: The
      individuals in the CAI group who performed balance training demonstrated better
      performance than control participants on baseline adjusted posttraining measures
      of dynamic balance in the anterior medial (P = .021), medial (P = .048), and
      posterior medial directions (P = .030); motoneuron pool excitability Hmax/Mmax
      ratio (P = .044) and single-limb presynaptic inhibition (P = .012); and joint
      position sense inversion variable error (P = .017). It may be of note that no
      systematic differences were detected for static balance or plantar flexion joint
      position sense tasks. CONCLUSIONS: After 6 weeks of balance training, individuals
      with CAI demonstrated enhanced dynamic balance, inversion joint position sense,
      and changes in motoneuron pool excitability compared to healthy controls who did
      not train. LEVEL OF EVIDENCE: Therapy, level 2b.

PMID- 21169717
TI  - Quantifying strain on posterior shoulder tissues during 5 simulated clinical
      tests: a cadaver study.
AB  - STUDY DESIGN: Controlled laboratory study using a repeated-measures approach.
      OBJECTIVE: To quantify the amount of strain on cadaver posterior shoulder tissues
      during simulated clinical tests across different tissue conditions. BACKGROUND:
      Several clinical tests are used to quantify posterior glenohumeral joint (GHJ)
      tissue tightness; however, the ability of these tests to directly assess the
      flexibility or tightness of the posterior capsule has not been evaluated.
      METHODS: The middle and lower regions of the posterior shoulder tissues were
      instrumented with strain gauges on 8 cadaver shoulder specimens. Strain was
      quantified on the posterior shoulder muscles, on the native posterior GHJ capsule
      (baseline condition), and on the posterior GHJ capsule after it was
      experimentally contracted using thermal energy. Five simulated clinical tests
      were compared across each of the 3 conditions: humerus cross-body adduction, and
      GHJ internal rotation with the humerus positioned in 4 combinations of plane and
      elevation angle. Repeated-measures analyses of variance were used to compare
      strain measured during the 5 simulated clinical tests across the 3 conditions,
      and to evaluate the change in strain after contracting the posterior capsule.
      RESULTS: There was a statistically significant interaction between tests and
      conditions for the middle region of the posterior shoulder. In the experimentally
      contracted condition, strain was greater when GHJ internal rotation was added to
      humerus flexion than when GHJ internal rotation was added to humerus abduction.
      There was a statistically significant main effect of tests at the lower region of
      the posterior shoulder, with internal rotation in abduction and internal rotation
      in the GHJ resting position demonstrating greater strain than cross-body
      adduction. The percent change in strain between the baseline and contracted
      capsule conditions did not reach statistical significance at either region.
      CONCLUSION: Strain on an experimentally contracted posterior GHJ capsule is
      highest when tested with a combination of GHJ internal rotation and humerus
      flexion.

PMID- 21169718
TI  - Thermal and pressure pain sensitivity in patients with unilateral shoulder pain:
      comparison of involved and uninvolved sides.
AB  - STUDY DESIGN: Cross-sectional. BACKGROUND: In the examination of patients with
      unilateral shoulder pain, pain provocation testing to compare the involved and
      uninvolved sides has been considered useful. However, side-to-side comparisons of
      experimental pain sensitivity in patients with unilateral shoulder pain are not
      widely reported in the literature. OBJECTIVES: To compare experimental pain
      sensitivity between the involved and uninvolved sides in patients with unilateral
      shoulder pain. METHODS: In consecutive patients seeking operative treatment for
      shoulder pain, sensitivity measures of bilateral pressure pain threshold at the
      shoulder and forearm, and thermal pain threshold, tolerance, and temporal
      summation at the forearm, were examined. Pressure sensitivity was tested with a
      Fischer pressure algometer, and thermal sensitivity with a computer-controlled
      Medoc neurosensory analyzer. The involved and uninvolved sides were compared with
      an analysis of variance. Influence of sex and location of testing were considered
      as covariates in the analysis. RESULTS: Fifty-nine consecutively recruited
      participants completed experimental pain sensitivity testing. Participants
      reported significantly lower pressure pain thresholds in the involved side
      compared to the uninvolved side (F1,56 = 4.96, P = .030). In addition, female
      compared to male participants demonstrated lower pressure pain thresholds in the
      bilateral shoulder regions (F1,56 = 10.84, P = .002). There was no difference in
      thermal pain sensitivity between sides. Average clinical pain intensity was
      negatively correlated with pressure pain threshold at the involved local site (r
      = -0.284, P = .029), indicating an influence of clinical pain intensity on local
      pressure pain. CONCLUSION: The results of this study provide evidence for higher
      experimental pressure pain sensitivity in the involved side of patients with
      unilateral shoulder pain and no difference between sides for thermal pain
      sensitivity. Females demonstrated higher pain sensitivity than males to pressure
      stimuli at the local shoulder region but not at the distal regions. Future
      studies should incorporate multiple stimuli when describing the pain profile of
      clinical populations.

PMID- 21169720
TI  - Identification of a high-risk anterior tibial stress fracture.
AB  - The patient was a deployed 34-year-old female soldier with a chief complaint of
      bilateral anterior shin pain for the past 8 weeks. Due to concern for a stress
      fracture, radiographic views of the bilateral tibia and fibula were completed,
      which revealed cortical thickening through the anterior midtibial regions
      bilaterally, consistent with stress reactive changes. Furthermore, a transverse
      lucency through the anterior cortex of the anterior right midtibial region was
      noted, which was consistent with a stress fracture. The patient was immediately
      placed in a short leg cast and was given strict non-weight-bearing instructions
      for gait. She was subsequently evacuated to her home duty station for
      consultation with an orthopaedic surgeon to determine if surgical intervention
      was warranted. This report illustrates the importance of identifying stress
      fractures considered to be high risk.

PMID- 21169721
TI  - Femoral neck stress fracture in a military trainee.
AB  - The patient was a 21-year-old female who was currently enrolled in a military
      security forces training program. She had a 1-month history of worsening left
      anterior hip pain that was insidious in nature and limiting her ability to run.
      The patient was diagnosed as having a left hip strain, prescribed a nonsteroidal
      anti-inflammatory medication,given a reduced activity waiver, and referred to a
      physical therapist. Despite previous radiographs of the pelvis and hips that were
      interpreted as normal, the history and physical examination findings led the
      physical therapist to be concerned about the presence of a possible femoral neck
      stress fracture. Immediate magnetic resonance imaging of the left hip was
      obtained, which revealed a stress fracture of the basicervical portion of the
      left femoral neck. The patient was referred to an orthopaedic surgeon for an
      expedited consultation and underwent open reduction internal fixation of the left
      hip later that day. After a period of convalescence and completion of a
      comprehensive rehabilitation program, the patient successfully returned to full
      military duty without limitations.

PMID- 21169725
TI  - Mast cells play a key role in Th2 cytokine-dependent asthma model through
      production of adhesion molecules by liberation of TNF-alpha.
AB  - Mast cells are well recognized as key cells in allergic reactions, such as asthma
      and allergic airway diseases. However, the effects of mast cells and TNF-alpha on
      T-helper type 2 (Th2) cytokine-dependent asthma are not clearly understood.
      Therefore, an aim of this study was to investigate the role of mast cells on Th2
      cytokine-dependent airway hyperresponsiveness and inflammation. We used
      genetically mast cell-deficient WBB6F1/J-Kitw/Kitw-v (W/Wv), congenic normal
      WBB6F1/J-Kit+/Kit+ (+/+), and mast cell-reconstituted W/Wv mouse models of
      allergic asthma to investigate the role of mast cells in Th2 cytokine-dependent
      asthma induced by ovalbumin (OVA). And we investigated whether the intratracheal
      injection of TNF-alpha directly induce the expression of ICAM-1 and VCAM-1 in
      W/Wv mice. This study, with OVA-sensitized and OVA-challenged mice, revealed the
      following typical histopathologic features of allergic diseases: increased
      inflammatory cells of the airway, airway hyperresponsiveness, and increased
      levels of TNF-alpha, intercellular adhesion molecule (ICAM)-1, and vascular
      cellular adhesion molecule (VCAM)-1. However, the histopathologic features and
      levels of ICAM-1 and VCAM-1 proteins in W/Wv mice after OVA challenges were
      significantly inhibited. Moreover, mast cell-reconstituted W/Wv mice showed
      restoration of histopathologic features and recovery of ICAM-1 and VCAM-1 protein
      levels that were similar to those found in +/+ mice. Intratracheal administration
      of TNF-alpha resulted in increased ICAM-1 and VCAM-1 protein levels in W/Wv mice.
      These results suggest that mast cells play a key role in a Th2 cytokine-dependent
      asthma model through production of adhesion molecules, including ICAM-1 and VCAM
      1, by liberation of TNF-alpha.

PMID- 21169726
TI  - Differential effects of down-regulated steroidogenic factor-1 on basal and
      angiotensin II-induced aldosterone secretion.
AB  - Aldosterone synthase (CYP11B2) is responsible for the final step in aldosterone
      synthesis and is importantly regulated by angiotensin-II (Ang II) through diverse
      pathways. However, under pathological conditions, such as in hyperaldosteronism,
      the regulation becomes disordered. The transcription factor steroidogenic factor
      1 (SF-1) is important in regulating the endocrine system and is overexpressed in
      aldosterone-producing adenoma (APA), a common cause of hyperaldosteronism.
      Overexpression of SF-1 has been extensively studied, but little in-depth
      information is available regarding the effects of inhibitory SF-1 on CYP11B2 and
      Ang II. In this paper, we have investigated the roles of down-regulated SF-1 in
      basal and Ang II-induced CYP11B2 expression using SF-1-specific short hairpin
      RNA. Inhibitory SF-1 was found to decrease the sensitivity of CYP11B2 and
      aldosterone to Ang II stimulation, whereas a down-regulation of SF-1 enhanced
      basal CYP11B2 expression and aldosterone production in H295R cells. Considering
      these differential effects of SF-1 on aldosterone production, these results might
      provide a new insight into the understanding of hyperaldosteronism.

PMID- 21169727
TI  - Simultaneous evaluation of the circulating levels of both Th1 and Th2 chemokines
      in patients with autoimmune Addison's disease.
AB  - BACKGROUND: Chemokines play a key role in the recruitment of the immune cells
      into the autoimmune process. Thus, the simultaneous evaluation of circulating
      levels of Th1-related chemokines, such as CX chemokine ligand 10 (CXCL10) and
      macrophage inflammatory proteins 1alpha (CCL3/MIP-1alpha), and Th2-related
      chemokines, such as macrophage inflammatory proteins 1 beta (CCL4/MIP-1beta)
      could be useful in the approach to some autoimmune diseases, including autoimmune
      Addison's disease (AAD). AIM: To evaluate plasmatic levels of MIP-1alpha, MIP
      1beta, CXCL10 and adrenocortical antibodies in patients with AAD under treatment
      with corticosteroids. PATIENTS AND METHODS: Twelve women and 5 men (group 1) were
      divided in 2 subgroups: 9 subjects with isolated AAD (group 1a) and 8 with AAD
      associated with chronic autoimmune thyroiditis (group 1b). MIP-1alpha, MIP- 1beta
      and CXCL10 were evaluated in the serum of all patients and in 20 healthy
      controls, using a system for microarray suspension. RESULTS: The levels of MIP
      1alpha, MIP-1beta and CXCL10 resulted significantly increased vs controls
      (p<0.001). An inverse significant correlation between the serum levels of MIP-
      1beta and the duration of the disease was observed. CONCLUSION: High levels of
      MIP-1alpha and MIP-1beta associated with increased levels of CXCL10 in AAD seem
      to indicate a role of these chemokines in the autoimmune pathology of adrenal
      gland through the recruitment in loco of Th1 and Th2 cells. The simultaneous
      measurement of Th1-related chemokines (CXCL10 and MIP-1alpha) and of Th2-related
      chemokine MIP-1beta in the serum of patients with AAD would sustain a novel
      preliminary hypothesis on the immune microenvironment of chronic autoimmune
      inflammation within adrenal glands.

PMID- 21169728
TI  - Adiponectin and bone metabolism markers in female rowers: eumenorrheic and oral
      contraceptive users.
AB  - This study investigated whether adiponectin, bone formation (osteocalcin) and
      bone resorption [type I carboxyterminal telopeptide (ICTP)] values are influenced
      by menstrual cycle phase and oral contraceptive use in female rowers. Twenty-four
      rowers divided into normally cycling athletes (NOC; no.=15) and athletes taking
      oral contraceptive pills (OC; no.=9) participated in this study. Fasting blood
      samples, body composition and aerobic capacity measurements were taken during the
      follicular (FP) and the luteal (LP) phases of the menstrual cycle. Adiponectin,
      insulin, glucose, insulin resistance, body composition and aerobic capacity did
      not fluctuate significantly during menstrual cycle in both groups. Osteocalcin
      and ICTP were lower (p<0.05) in OC compared with NOC, but did not change
      significantly across menstrual cycle phases in both groups. Estradiol and
      progesterone were not related to adiponectin, osteocalcin or ICTP (r<0.147;
      p>0.05). Adiponectin was correlated (p<0.05) with osteocalcin (r=0.452) and fat
      free mass (r=0.428), and osteocalcin was related (p<0.05) to insulin (r=-0.413),
      glucose (r=-0.486) and insulin resistance (r=-0.528). In conclusion, adiponectin
      was not affected by menstrual cycle phase and OC use in female rowers, while bone
      metabolism markers were lower in OC compared to NOC groups. Adiponectin and
      osteocalcin were interrelated and may characterise energy homeostasis in female
      athletes.

PMID- 21169729
TI  - Follicular nodules (THY3) of the thyroid: we recommend surgery.
AB  - OBJECTIVE: To determine the need of total thyrodectomy for patients with
      follicular nodules of thyroid. SUBJECTS AND METHODS: From January 2005 through
      June 2008, 2249 consecutive patients (438 males, 1811 females; mean age 54 yr,
      range 9-87) with thyroid nodules were submitted to 2518 ultrasound-guided fine
      needle aspiration (USgFNA) for cytological examination. USgFNA were performed by
      experienced surgeon (RP) and endocrinologist (RGG) under ultra- sonographyc
      guidance, using a 10-MHz linear transducer. Liquid-based cytology was used.
      RESULTS: All cytological samples were classified in 5 diagnostic classes (THY1,
      THY2, THY3, THY4, THY5) in agreement with the British Thyroid Association (BTA);
      1.4% specimen were classified as THY5, 2.1% as THY4, 7.6% as THY3, 79.5% as THY2
      and 9.4% as THY1. In 97% of THY5 patients, malignancy was found. Among THY4
      patients, 95.5% were positive for thyroid tumor. Among THY3 patients, malignancy
      was found in 29.1%. THY3 patients with thyroid tumors were younger than those
      with benign lesions (46 +/- 14.1 yr vs 50 +/- 13.8 yr; p<0.05, t test). No
      statistical difference was found neither in malignancy frequency among men and
      women nor in mean size of nodules (24 +/- 11.8 mm malignant vs 23 +/- 9.4 mm
      benign). CONCLUSIONS: this study provides evidence that USgFNA offers a very
      sensitive and accurate method in reducing THY1 samples and in detecting
      malignancy (>95% both in THY5 and THY4, and >29% in THY3 lesions). Our proposal
      is to submit to total thyroidectomy all patients with THY5 and THY4 lesions and
      THY3 thyroid nodule >1 cm.

PMID- 21169730
TI  - Genotype, phenotype and hormonal levels correlation in non-classical congenital
      adrenal hyperplasia.
AB  - Non-classical congenital adrenal hyperplasia (NCAH) is a morbid condition
      sustained by the reduced function of one of the enzymes involved in the adrenal
      steroid biosynthesis pathway, mainly the 21-hydroxylase. Different degrees of
      enzyme activity impairment determine different clinical pictures, with childhood
      or post-pubertal onset. The aim of this study was to evaluate the relationship
      between genotype, phenotype, and adrenal hormonal levels in a group of 66
      patients affected by NCAH attending outpatient pediatric or endocrinological
      Clinics. Our findings show that age at pubarche/menarche was significantly
      younger, height SD score) and Delta bone age-chronological age were significantly
      higher in patients with a more severe enzyme activity impairment, while cutaneous
      androgenization and menstrual irregularities in post-pubertal girls were not
      related to the grading of genotype.

PMID- 21169731
TI  - Systemic adverse events following rituximab therapy in patients with Graves'
      disease.
AB  - BACKGROUND AND AIM: Rituximab (RTX) therapy has shown promising results in
      Graves' disease (GD), with or without ophthalmopathy. We examined the occurrence
      of adverse events in GD patients treated with RTX. SUBJECTS AND METHODS: Ten
      patients received RTX and methimazole, while 10 patients received methimazole
      only. Adverse events were recorded, and the presence of circulating immune
      complexes (CIC) was measured as IgG, IgM and complement component 3 (C3)
      depositing on normal monocytes following incubation with patient plasma. RESULTS:
      Five patients had benign infusion-related adverse events at first infusion. Two
      patients developed a serum sickness-like reaction 11 days after the first RTX
      infusion. One of these patients developed diarrhea, raised orosomucoid levels,
      lowgrade inflammation in colonoscopic biopsies, and iridocyclitis 1 yr later. At
      day 14, the most pronounced immunoglobulin/ C3-adherent to the test monocytes,
      indicative of CIC, was observed in the presence of plasma from these 2 patients
      (p=0.003 to p=0.01 vs asymptomatic patients). A 3rd patient had recurrent fever
      and symmetric polyarthritis from day 38, and colonoscopy-verified ulcerative
      colitis at day 68. This patient had the 3rd highest increase in Ig deposition on
      monocytes by day 14. The arthralgias persisted in 2 of the patients, despite
      glucocorticoid rescue therapy. CONCLUSIONS: We report articular adverse events in
      3 and gastrointestinal symptoms in 2 out of 10 GD patients who received RTX
      without concurrent immunosupression. The joint symptoms were related to CIC
      formation.

PMID- 21169732
TI  - A large view of CYP21 locus among Sicilians and other populations: identification
      of a novel CYP21A2 variant in Sicily.
AB  - BACKGROUND: Several mutations in CYP21 locus cause 21-hydroxylase deficiency (21
      OHD). The most common mutations are widespread among different geographic areas
      and their frequencies have been also reported to differ among certain
      populations. AIM: To obtain a large view on the frequencies of the most common
      mutations in the CYP21 locus, in Sicily, in the Mediterranean and other major
      geographic areas worldwide. SUBJECTS AND METHODS: Three hundred and eight
      unrelated CYP21A2 alleles leading 21-OHD in Sicily were genetically typed and
      compared with other series previously reported in Sicily and in surrounding
      regions. An analysis of the frequencies of the different geographic areas was
      also carried out. CYP21A2 typing was carried out using PCR-restriction fragment
      length polymorphism (RFLP), for the detection of the CYP21A2 deletion, while
      sequencing analysis was performed to evaluate all the missense/non-sense
      mutations. RESULTS: Our study revealed that p.V281L (44.4%), I2splice (21.6%) and
      p.P30L (11.2%) were very frequent alleles, del8bp (0.4%) was found very rarely in
      Sicily and a novel mutation leading to non-classical phenotype, p.L198F, was also
      discovered in this population. Allele frequencies were found to be significantly
      different from previously observed frequencies in Sicily. In addition, here we
      present the most significant frequency modifications among different geographic
      areas worldwide. CONCLUSIONS: As the distribution of the disease CYP21A2 alleles
      is heterogeneous around the world, the knowledge of the relative distributions
      allows a better management of 21-OHD for fetuses and newborns in different
      geographic areas.

PMID- 21169735
TI  - Lesions of anogenital mammary-like glands: an update.
AB  - Long considered to be ectopic breast tissue representing the caudal remnants of
      the milk ridges, anogenital mammary-like glands are nowadays thought to represent
      a normal constituent of the anogenital area. Lesions involving these glands,
      benign or malignant, epithelial or stromal manifest a striking similarity to
      their mammary counterparts. This review addresses the recent literature on
      lesions of anogenital mammary-like glands and our personal experience with
      various lesions related to these structures. Discussed are the normal anatomy and
      histology of these glands as well as the clinical presentation, histopathological
      and immunohistochemical features, molecular biological aspects, and differential
      diagnosis of various lesions involving anogenital mammary-like glands, including
      lactating adenoma, hidradenoma papilliferum, hidradenocarcinoma papilliferum,
      fibroadenomas, phyllodes tumor, pseudoangiomatous stromal hyperplasia,
      extramammary Paget disease, and other carcinomas. In addition, "nonspecific"
      epithelial or stromal changes some of which can be likened to similar changes
      occurring in a range of benign breast disease, including sclerosing adenosis,
      columnar cell lesions, ductal lesions and various metaplastic changes affecting
      epithelium and myoepithelium are discussed. Although lesions of anogenital
      mammary-like glands are often discussed in many dermatopathology textbooks in the
      context of cutaneous adnexal neoplasms we advocate that the best approach to the
      diagnosis of these lesions is to relate them to analogous well recognized lesions
      occurring in the breast, that is, through the eyes of a breast pathologist. This
      will enable their recognition, precise classification and should introduce
      greater uniformity in how they are reported in the literature so that more
      meaningful clinicopathological comparisons and correlations may be made.

PMID- 21169734
TI  - Atg35, a micropexophagy-specific protein that regulates micropexophagic apparatus
      formation in Pichia pastoris.
AB  - Autophagy-related (Atg) pathways deliver cytosol and organelles to the vacuole in
      double-membrane vesicles called autophagosomes, which are formed at the
      phagophore assembly site (PAS), where most of the core Atg proteins assemble.
      Atg28 is a component of the core autophagic machinery partially required for all
      Atg pathways in Pichia pastoris. This coiled-coil protein interacts with Atg17
      and is essential for micropexophagy. However, the role of Atg28 in micropexophagy
      was unknown. We used the yeast two-hybrid system to search for Atg28 interaction
      partners from P. pastoris and identified a new Atg protein, named Atg35. The
      atg35? mutant was not affected in macropexophagy, cytoplasm-to-vacuole targeting
      or general autophagy. However, both Atg28 and Atg35 were required for
      micropexophagy and for the formation of the micropexophagic apparatus (MIPA).
      This requirement correlated with a stronger expression of both proteins on
      methanol and glucose. Atg28 mediated the interaction of Atg35 with Atg17.
      Trafficking of overexpressed Atg17 from the peripheral ER to the nuclear envelope
      was required to organize a peri-nuclear structure (PNS), the site of Atg35
      colocalization during micropexophagy. In summary, Atg35 is a new Atg protein that
      relocates to the PNS and specifically regulates MIPA formation during
      micropexophagy.

PMID- 21169736
TI  - Histologic grading and prognostic biomarkers in salivary gland carcinomas.
AB  - Both the variety and rarity of salivary gland carcinomas pose challenge for using
      histologic grade and biomarkers to predict outcome. Mucoepidermoid carcinoma is
      the histologic subtype for which grading is most prognostically and
      therapeutically relevant. This tumor is graded using standard schemes in a 3-tier
      manner with the intermediate-grade category shows the most variability between
      grading systems and thus the most controversy in management. The t(11;19)(q21;
      p13) MECT1-MAML2 translocation may be an objective marker that can help to
      further stratify difficult cases. Adenoid cystic carcinomas are graded based on
      pattern with solid areas correlating with a worse prognosis. Occasionally,
      adenoid cystic carcinomas may undergo transformation to highly aggressive
      pleomorphic high-grade carcinomas with frequent nodal metastases. Comparative
      genomic hybridization has revealed several chromosomal regions (such as 1p32-p36,
      6q23-q27) of prognostic interest in adenoid cystic carcinoma. Carcinoma ex
      pleomorphic adenoma is actually a category of tumors rather than a single tumor
      type with both aggressive and indolent versions. These tumors should be further
      qualified as to type/grade of carcinoma and extent, as intracapsular and
      minimally invasive tumors behave favorably. Acinic cell carcinomas, although
      generally considered low grade, can recur, metastasize, or even prove lethal in a
      significant number of cases suggesting amenability to a grading scheme to
      separate these biologic groups. Although aggressive histologic parameters
      (anaplasia, necrosis, and mitoses) are predictive of poor outcome, a standard
      grading scheme does not yet exists. Acinic cell carcinomas can also undergo high
      grade transformation.

PMID- 21169733
TI  - The filamins: organizers of cell structure and function.
AB  - Filamin A (FLNa), the first non-muscle actin filament cross-linking protein, was
      identified in 1975. Thirty five years of FLNa research has revealed its structure
      in great detail, discovered its isoforms (FLNb and c), and identified over 90
      binding partners including channels, receptors, intracellular signaling
      molecules, and even transcription factors. Due to this diversity, mutations in
      human FLN genes result in a wide range of anomalies with moderate to lethal
      consequences. This review focuses on the structure and functions of FLNa in cell
      migration and adhesion.

PMID- 21169737
TI  - Comprehensive evaluation of colorectal polyps in specimens from endoscopic
      biopsies.
AB  - Modern evaluation of specimens from biopsies of colorectal polyps has become
      increasingly complex because of tremendous progress in the understanding of
      colorectal neoplasia. Although pathologists are generally familiar with the basic
      handling of carcinoma in the setting of polypectomies or resections, the
      comprehensive evaluation of specimens from biopsies of colorectal polyps obtained
      with forceps is far from intuitive and has yet to be reviewed. Comprehensive
      evaluation requires always addressing several key issues, even when dealing with
      seemingly routine cases. These issues include taking further action when initial
      sections lack polyps, accurately quantitating polyps, accurately classifying
      polyps, determining whether thresholds are met for considering conditions at high
      risk for carcinoma, detecting incidental findings other than polyps, and
      determining which incidental findings are clinically significant. In particular,
      polyposis with attenuated phenotype or Lynch syndrome may be clinically occult,
      and the possibility of these entities should always be kept in mind, regardless
      of age or history. Ancillary studies performed immediately on carcinoma that is
      detected at biopsy guides surgery, guides medical therapy, prognosticates,
      provides evidence for hereditary neoplasia, and guides surveillant colonoscopy
      for the family.

PMID- 21169738
TI  - HER2 testing in gastric cancer.
AB  - Molecular therapies targeting HER2 are part of the established drug armamentarium
      in breast carcinoma. Now the ToGA trial, an international multicenter phase III
      clinical study, involving 24 countries globally, has shown that the anti-HER2
      humanized monoclonal antibody Trastuzumab is effective in prolonging survival in
      HER2-positive carcinoma of the stomach and the gastroesophageal junction (GEJ).
      Similarly to breast carcinoma, >20% of gastric cancers show HER2 overexpression
      and/or amplification, and this percentage increases to 33% in GEJ tumors. Thus,
      as in breast carcinoma, pathologists are now asked to evaluate HER2 status in
      gastric carcinoma samples. As validated in the ToGA trial, the HER2 testing
      criteria that must be used in evaluating both gastric carcinoma biopsies and
      surgical specimens significantly differ from those routinely applied in breast
      carcinoma. The main variations with regard to the pattern of reactivity in HER2
      expressing cells are as follows: the completeness of membrane staining is not a
      "conditio sine qua non" and the number of stained cells necessary to consider a
      case as positive is different. We must also take note of the much more frequent
      heterogeneity of HER2 positivity in gastric cancer compared with breast carcinoma
      and the less stringent correlation between HER2 amplification and protein
      overexpression that is observed in gastric carcinoma, where more than 20% of
      cases may carry HER2 amplification, although of low level, without HER2
      expression. In these patients, in the ToGA trial, there was no apparent benefit
      from adding Trastuzumab to chemotherapy: for this reason the European Medicines
      Agency, while approving usage of Trastuzumab for metastatic adenocarcinoma
      treatment, indicated HER2 testing by immunohistochemistry as first evaluation
      assay, followed by fluorescence in situ hybridization in 2+ equivocal cases. HER2
      testing in gastric carcinoma is a new field, opening several opportunities: for
      patients with gastric cancer, this is a new promising therapeutic option; for
      pathologists, strengthening our role in therapy selection and emphasizing our
      duty of providing accurate and reproducible HER2 testing results; for all
      interested in understanding the biology of gastric and GEJ cancer and in
      discovering new possible molecular therapy targets.

PMID- 21169739
TI  - Heterologous and rare homologous sarcomas of the uterine corpus: a
      clinicopathologic review.
AB  - Pure sarcomas of the uterine corpus are uncommon, constituting less than 3% of
      all malignancies at this site, and most of them are leiomyosarcomas and
      endometrial stromal sarcomas. Rare histotypes of homologous sarcomas and
      heterologous sarcomas are occasionally encountered, and the absence of
      significant accumulated experience with these histotypes at this location may
      potentially raise diagnostic and patient management difficulties. In this
      article, the clinicopathologic attributes of all earlier reported sarcomas of the
      uterine corpus other than leiomyosarcomas and endometrial stromal sarcomas are
      summarized. Included are embryonal rhabdomyosarcoma, pleomorphic
      rhabdomyosarcoma, angiosarcoma, alveolar soft part sarcoma, malignant
      perivascular epithelioid cell tumors (PEComas), osteosarcoma, chondrosarcoma,
      liposarcomatous tumors, malignant extrarenal rhabdoid tumors, Ewing
      sarcoma/primitive neuroectodermal tumor, and other rare histotypes. Embryonal
      rhabdomyosarcoma (20%), Ewing sarcoma/primitive neuroectodermal tumor (17%),
      angiosarcoma (14%), and pleomorphic rhabdomyosarcoma (13%) appeared to be more
      common than the others, although there was no single overwhelmingly prevalent
      histotype in the group. A subset, including embryonal rhabdomyosarcoma, alveolar
      soft part sarcoma, and PEComas, peak in the premenopausal years, but most of the
      others were observed in postmenopausal women. Favorable outcomes have been
      reported for the patients diagnosed with alveolar soft part sarcoma, and the
      prognosis for their counterparts with PEComa remains a matter of debate.
      Multimodal therapeutic approaches to contemporary patients with embryonal
      rhabdomyosarcomas have resulted in significantly improved outcomes.
      Unfortunately, most of the other sarcomas have been associated with rapid tumor
      progression and unfavorable patient outcomes. The differential diagnosis for
      these sarcomas is often extensive and varies by histotype, but their accurate
      diagnosis fundamentally requires the careful exclusion of biphasic malignancies.

PMID- 21169740
TI  - Are you responsible for medical director duties in anatomic pathology--and why
      should you care?
AB  - For many pathologists, the roles of the medical director are not clearly
      distinguished from other medical leadership and management duties, such as those
      of the chair of pathology or a section head of anatomic pathology. We describe
      the evolution in the understanding of the roles of the medical director as
      defined by the Clinical Laboratory Improvement Amendments of 1988 and separate
      from the roles of the chair of pathology, department chair, division chair, and a
      section head in anatomic pathology in our institution. Delineation of the roles
      of medical director, department chair, chair of anatomic pathology division, and
      a section head of a subdivision in anatomic pathology has helped us to understand
      the roles and ensure that all duties are fulfilled for patient care and for
      compliance and regulation.

PMID- 21169741
TI  - Urothelial neoplasms of the urinary bladder occurring in young adult and
      pediatric patients: a comprehensive review of literature with implications for
      patient management.
AB  - Bladder urothelial carcinoma is typically a disease of older individuals and
      rarely occurs below the age of 40 years. There is debate and uncertainty in the
      literature regarding the clinicopathologic characteristics of bladder urothelial
      neoplasms in younger patients compared with older patients, although no
      consistent age criteria have been used to define "younger" age group categories.
      Use of the World Health Organization 2004/International Society of Urological
      Pathology 1998 grading nomenclature and recent molecular studies highlight
      certain unique features of bladder urothelial neoplasms in young patients,
      particularly in patients below 20 years of age. In this meta-analysis and review,
      the clinical, pathologic, and molecular features and risk factors of bladder
      urothelial neoplasms in patients 40 years or less are presented and analyzed
      according to decades of presentation. Similar to older patients, bladder
      urothelial neoplasms in patients 40 years or younger occur more common in male
      patients, present mainly with gross painless hematuria, and are more commonly
      located at bladder trigone/ureteral orifices, but in contrast have a greater
      chance for unifocality. Delay in diagnosis of bladder urothelial neoplasms seems
      not to be uncommon in younger patients probably because of its relative rarity
      and the predominance of benign causes of hematuria in this age group causing
      hesitancy for an aggressive work-up. Most tumors in patients younger than 40
      years were low grade. The incidence of low-grade tumors was the lowest in the
      first 2 decades of life, with incremental increase of the percentage of high
      grade tumors with increasing age decades. Classification according to the World
      Health Organization 2004/International Society of Urological Pathology grading
      system identified papillary urothelial neoplasms of low malignant potential to be
      relatively frequent among bladder tumors of young patients particularly in the
      teenage years. Similar to grade, there was marked predominance of low stage
      tumors in the first 2 decades of life with gradual inclusion of few higher stage
      and metastatic tumors in the 2 older decades. Bladder urothelial neoplasms
      occurring in patients <20 years of age lack or have a much lower incidence of
      aberrations in chromosome 9, FGFR3, p53, and microsatellite instability and have
      fewer epigenetic alterations. Tumor recurrence and deaths were infrequent in the
      first 2 decades and increased gradually in each successive decade, likely
      influenced by the increased proportion of higher grade and higher stage tumors.
      Our review of the literature shows that urothelial neoplasms of the bladder
      occurring in young patients exhibit unique pathologic and molecular features that
      translate to its more indolent behavior; this distinction is most pronounced in
      patients <20 years. Our overall inferences have potential implications for
      choosing appropriate noninvasive diagnostic and surveillance modalities, whenever
      feasible, and for selecting suitable treatment strategies that factor in quality
      of life issues vital to younger patients.

PMID- 21169742
TI  - The spectrum of papillary thyroid carcinoma variants.
AB  - Papillary thyroid carcinoma is the most common type of thyroid malignancy. The
      diagnostic features of these tumors include characteristic nuclear cytology.
      However, many variants have been reported with different morphology and molecular
      profiles. Although the vast majority of papillary thyroid carcinomas have an
      excellent prognosis, some variants of papillary thyroid carcinoma can have a more
      aggressive course. With this increased attention to papillary thyroid carcinoma
      variants has come the need to sort out which variants are clinically important
      and should be recognized by practicing pathologists. The main objectives of this
      review article are to (1) summarize the gross and histopathologic features of
      papillary thyroid carcinoma; (2) provide an overview of the subtypes of papillary
      thyroid carcinoma and their prognosis; (3) discuss established and emerging data
      on the immunohistochemical findings that are helpful in differential diagnosis;
      and (4) summarize molecular findings and pathogenesis of these lesions.

PMID- 21169743
TI  - Selected case from the Arkadi M. Rywlin International Pathology Slide Seminar:
      benign lymphoepithelial cyst, head of pancreas.
AB  - Pancreatic lymphoepithelial cysts are more common in men, can occur anywhere in
      the pancreas, are sharply demarcated from surrounding tissues, and range in size
      from 1.2 to 17 cm. Patients are usually middle aged, presenting symptoms include
      abdominal pain, nausea, vomiting, and diarrhea, although many tumors are
      asymptomatic and are discovered incidentally on organ imaging or at autopsy. An
      elevated serum carbohydrate-associated antigen 19-9 may wrongly suggest a
      mucinous neoplasm. The diagnosis can be made preoperatively with a combination of
      organ imaging, fine needle aspiration biopsy, or ultrasound-guided Trucut
      biopsies. Cysts can be unilocular, bilocular, or multilocular, have walls up to
      0.6 cm thick which are lined by squamous epithelium, occasional columnar mucinous
      cells, and small foci of sebaceous cells. The epithelium is surrounded by a dense
      rim of lymphoid tissue with scattered lymphoid follicles. Invaginations of the
      epithelium into the lymphoid tissue, reminiscent of a Warthin tumor, are
      occasionally observed. The pathogenesis is unknown. Pancreatic lymphoepithelial
      cysts are cured by conservative resection but if they are asymptomatic and are
      diagnosed before surgery, no treatment is necessary.

PMID- 21169744
TI  - The burden of prevalent vertebral fractures is negatively associated with
      functional outcome in women with hip fracture.
AB  - OBJECTIVE: The aim of this study was to investigate the association between the
      burden of prevalent vertebral fractures and functional outcome in women with hip
      fracture. DESIGN: We investigated 164 of 180 women with hip fracture admitted
      consecutively to a rehabilitation hospital. Lateral radiographs of the spine were
      taken 20.0 +/- 5.1 days (mean +/- SD) after fracture occurrence. To obtain a
      summary measure of vertebral fracture burden, we calculated the spinal deformity
      index by summing the fracture grades of all vertebrae (T4 to L4), assessed using
      Genant's method. Functional outcome was assessed using Barthel index scores.
      RESULTS: In a Spearman rank test, we observed a significant negative correlation
      between spinal deformity index scores and Barthel index scores at discharge from
      rehabilitation (rho = -0.23; P = 0.003). The association between spinal deformity
      index and Barthel index scores was confirmed (P = 0.039) after adjustment for
      eight potential confounders. Multiple regression also showed a significant
      negative association between spinal deformity index scores and increase in
      Barthel index scores during rehabilitation (P = 0.012). The panel of prognostic
      factors that we included in the multivariate analysis accounted for 62% of the
      variance in the Barthel index scores at discharge from rehabilitation and 43% of
      their increase during rehabilitation. CONCLUSIONS: The burden of prevalent
      vertebral fractures is negatively associated with functional outcome in women
      with hip fracture.

PMID- 21169745
TI  - Disability attitudes in health care: a new scale instrument.
AB  - OBJECTIVE: The aims of this study were to develop and validate an instrument
      measuring attitudes toward providing health care to patients with disability, to
      compare the attitudes of preclinical and clinical medical students, and to
      examine whether sex, a background in disability, or career interest in physical
      medicine and rehabilitation affect medical student attitudes toward working with
      patients with disability. DESIGN: A cross-sectional survey was conducted in an
      academic medical center with participants that included preclinical (n = 63) and
      clinical medical (n = 58) students, physical medicine and rehabilitation
      residents (n = 18), and internal medicine residents (n = 10). A 17-item
      Disability Attitudes in Health Care scale was developed based on existing,
      validated geriatrics attitudes scales. Attitudes Toward Disabled Persons Form O
      scale was used for correlation testing. Background demographic data collected
      from medical student respondents included sex, previous personal or work
      experience with disability, and career interest in physical medicine and
      rehabilitation. RESULTS: The new scale demonstrated high reliability (Cronbach
      alpha = 0.74) and criterion validity (correlation coefficient = 0.54 with the
      Attitude Towards Disabled Persons scale). Attitudes were no different between
      preclinical and clinical medical students. Male medical students had more
      negative attitudes than female students did (P = 0.03). Students with a higher
      level of career interest in physical medicine and rehabilitation scored higher
      than less interested students did (P = 0.015). CONCLUSIONS: The new Disability
      Attitudes in Health Care scale developed in this study shows good internal
      consistency and criterion validity. Attitudes toward caring for patients with
      disability seem to be unrelated to the standard medical education curriculum or
      previous experience with disability. Specific educational experiences may be
      designed to engender more positive attitudes toward providing health care to this
      patient population.

PMID- 21169746
TI  - Trends and challenges in the early rehabilitation of patients with traumatic
      brain injury: a Scandinavian perspective.

PMID- 21169747
TI  - European models of multidisciplinary rehabilitation services for traumatic brain
      injury.

PMID- 21169748
TI  - Rehabilitation of traumatic brain injury in Italy.

PMID- 21169749
TI  - The role of the European physiatrist in traumatic brain injury.

PMID- 21169751
TI  - Age and gender interactions in ultraendurance performance: insight from the
      triathlon.
AB  - PURPOSE: The purposes of this study were (i) to investigate the effect of age on
      gender difference in Hawaii Ironman triathlon performance time and (ii) to
      compare the gender difference among swimming (3.8 km), cycling (180 km), and
      running (42 km) performances as a function of age. METHODS: Gender difference in
      performance times and estimated power output in the three modes of locomotion
      were analyzed for the top 10 men and women amateur triathletes between the ages
      of 18 and 64 yr for three consecutive years (2006-2008). RESULTS: The gender
      difference in total performance time was stable until 55 yr and then
      significantly increased. Mean gender difference in performance time was
      significantly (P < 0.01) smaller for swimming (mean +/- 95% confidence interval =
      12.1% +/- 1.9%) compared with cycling (15.4% +/- 0.7%) and running (18.2% +/-
      1.3%). In contrast, mean gender difference in cycling estimated power output
      (38.6% +/- 1.1%) was significantly (P < 0.01) greater compared with swimming
      (27.5% +/- 3.8%) and running (32.6% +/- 0.7%). CONCLUSIONS: This cross-sectional
      study provides evidence that gender difference in ultraendurance performance such
      as an Ironman triathlon was stable until 55 yr and then increased thereafter and
      differed between the locomotion modes. Further studies examining the changes in
      training volume and physiological characteristics with advanced age for men and
      women are required to better understand the age-associated changes in
      ultraendurance performance.

PMID- 21169752
TI  - The importance of a correct study design to differentiate between two opposing
      models.

PMID- 21169754
TI  - Myocardial function in rowers.

PMID- 21169758
TI  - Ultrasound-guided peripheral nerve block in a patient with neurofibromatosis.

PMID- 21169759
TI  - Accurate placement of ultrasound-guided lateral popliteal-sciatic perineural
      catheters.

PMID- 21169760
TI  - Injection of injectates is more than just for "opening the perineural space".

PMID- 21169761
TI  - Continuous femoral nerve block under ultrasound guidance: perineural opening
      before catheter placement is perhaps no longer necessary.

PMID- 21169762
TI  - Ultrasound refraction artifact is unlikely a response to duplication of brachial
      plexus.

PMID- 21169763
TI  - Practical considerations in preparing the pig carcass spine phantom.

PMID- 21169764
TI  - Investigation of puncture angles needs clinically defined insertion points.

PMID- 21169766
TI  - Specialist's knowledge of local anesthetic systemic toxicity.

PMID- 21169768
TI  - Neurologic deficit in conjunction with intraneural injection: more questions than
      answers.

PMID- 21169769
TI  - An unsubstantiated condemnation of intraneural injection.

PMID- 21169770
TI  - Intraneural injections.

PMID- 21169771
TI  - Recognizing dangerous intraneural injection: is it the musician or the
      instrument?

PMID- 21169773
TI  - Educating residents in behavioral health care and collaboration: comparison of
      conventional and integrated training models.
AB  - PURPOSE: To determine whether former pediatric residents trained using a model of
      integrated behavioral health (BH) care in their primary care continuity clinics
      felt more comfortable managing BH care and better prepared to collaborate with BH
      professionals than did peers from the same residency who trained in clinics with
      a conventional model of BH care. METHOD: University of Rochester School of
      Medicine and Dentistry pediatric residents were assigned to one of two continuity
      clinic sites. At one site, psychology fellows and faculty were integrated into
      the clinic teams in the mid-1990s. At the other, conventional patterns of
      consultation and referral continued. In 2004, the authors surveyed 245 alumni
      (graduated 1989-2003) about their experiences and their comfort with providing BH
      care and collaborating with BH providers in their current practice. RESULTS: A
      total of 174 alumni (71%) responded. There were significant differences between
      graduates who trained in the two models. Those who trained in the integrated
      model were significantly more likely than others to report that they had
      consulted or planned treatment with a BH provider during residency and to report
      that their continuity clinic helped prepare them to collaborate with BH
      providers. They were somewhat more likely to believe that their overall residency
      training prepared them to manage BH issues in their current practice.
      CONCLUSIONS: These findings suggest that an integrated training environment,
      described in detail in the companion article in this issue, can enhance pediatric
      resident education in the management of BH problems and collaboration with BH
      specialists.

PMID- 21169774
TI  - Educating residents in behavioral health care and collaboration: integrated
      clinical training of pediatric residents and psychology fellows.
AB  - Pediatric residency practices face the challenge of providing both behavioral
      health (BH) training for pediatricians and psychosocial care for children. The
      University of Rochester School of Medicine and Dentistry and Rochester General
      Hospital developed a joint training program and continuity clinic infrastructure
      in which pediatric residents and postdoctoral psychology fellows train and
      practice together. The integrated program provides children access to BH care in
      a primary care setting and gives trainees the opportunity to integrate
      collaborative BH care into their regular practice routines. During 1998-2008, 48
      pediatric residents and 8 psychology fellows trained in this integrated clinical
      environment. The program's accomplishments include longevity, faculty and fiscal
      stability, sustained support from pediatric leadership and community payers, the
      development in residents and faculty of greater comfort in addressing BH problems
      and collaborating with BH specialists, and replication of the model in two other
      primary care settings. In addition to quantitative program outcomes data, the
      authors present a case example that illustrates how the integrated program works
      and achieves its goals. They propose that educating residents and psychology
      trainees side by side in collaborative BH care is clinically and educationally
      valuable and potentially applicable to other settings. A companion report
      published in this issue provides results from a study comparing the perceptions
      of pediatric residents whose primary care continuity clinic took place in this
      integrated setting with those of residents from the same pediatric residency who
      had their continuity clinic training in a nonintegrated setting.

PMID- 21169775
TI  - Teaching oral health in U.S. medical schools: results of a national survey.
AB  - PURPOSE: Good oral health is an important aspect of good overall health. Past
      studies show physicians have had limited oral health training. METHOD: In 2009,
      the authors sent a 22-question online survey to the deans of education of 126 MD
      granting and 28 DO-granting U.S. medical schools to determine the extent to which
      these schools have an oral health curriculum. RESULTS: Eighty-eight schools
      (57.1%) responded. Of these, 61 (69.3%) reported offering less than five hours of
      oral health curriculum; 9 (10.2%) offered no curriculum. Schools with greater
      than 150 students per class were more likely to offer five or more hours of oral
      health curriculum compared with small or midsize schools (P = .022). School
      location and having a dental school and/or residency were not significantly
      related to the number of hours of oral health curriculum (P = .728 and .271,
      respectively). Awareness of oral questions on the United States Medical Licensing
      Examination board exams and/or the Association of American Medical Colleges
      report on oral health education was also not associated with curriculum volume.
      In schools with an oral health curriculum, topics being covered ranged from 10.0%
      teaching hands-on skills training to 81.7% covering oral cancers. Only 29.9%
      reported evaluating students around oral health topics. CONCLUSIONS: The majority
      of the responding U.S. medical schools offer very little oral health education.
      There are few meaningful correlations as to what contributes to schools having a
      more robust curriculum. Further study is needed to explore how to improve this
      educational void.

PMID- 21169776
TI  - Increasing the supply of rural family physicians: recent outcomes from Jefferson
      Medical College's Physician Shortage Area Program (PSAP).
AB  - PURPOSE: The shortage of primary care physicians in rural areas is an enduring
      problem with serious implications for access to care. Although studies have
      previously shown that medical school rural programs-such as Jefferson Medical
      College's Physician Shortage Area Program (PSAP)-significantly increase the rural
      workforce, determining whether these programs continue to be successful is
      important. METHOD: The authors obtained, from the Jefferson Longitudinal Study,
      the 2007 practice location and specialty for the 2,394 PSAP and non-PSAP
      graduates of 11 previously unreported Jefferson graduating classes (1992-2002).
      They determined the relative likelihood both of PSAP versus non-PSAP graduates
      practicing rural family medicine and of all PSAP versus non-PSAP graduates
      practicing in Pennsylvania's rural counties. RESULTS: PSAP graduates were much
      more likely both to practice rural family medicine than their non-PSAP peers
      (32.0% [31/97] versus 3.2% [65/2,004]; relative risk [RR] = 9.9, confidence
      interval [CI] 6.8-14.4, P < .001) and to practice any specialty in rural
      Pennsylvania (PSAP 24.7% [24/97] versus non-PSAP 2.0% [40/2,004]; RR = 12.4, CI
      7.8-19.7, P < .001). CONCLUSIONS: Despite major changes in health care in recent
      decades, Jefferson's PSAP continues to represent a successful model for
      substantially increasing the supply and distribution of rural family physicians.
      Especially with the forthcoming expansion in health insurance, access to care for
      rural residents will require an increased supply of providers. These results may
      also be important for medical schools planning to develop similar rural programs,
      given the new Rural Physician Training Grants program.

PMID- 21169777
TI  - An academic-community partnership to improve care for the underserved.
AB  - Despite the need for a robust primary care workforce, the number of students and
      residents choosing general internal medicine careers continues to decline. In
      this article, the authors describe their efforts at the University of California,
      Davis School of Medicine to bolster interest in internal medicine careers and
      improve the quality of care for medically underserved populations through a
      tailored third-year residency track developed in partnership with the Sacramento
      County Department of Health and Human Services. The Transforming Education and
      Community Health (TEACH) Program improves continuity of care between inpatient
      and outpatient settings, creates a new multidisciplinary teaching clinic in the
      Sacramento County health system, and prepares residents to provide coordinated
      care for vulnerable populations. Since its inception in 2005, 25 residents have
      graduated from the TEACH Program. Compared with national rates, TEACH graduates
      are more likely to practice general internal medicine and to practice in
      medically underserved settings. TEACH residents report high job satisfaction and
      provide equal or higher-quality diabetes care than that indicated by national
      benchmarks. The authors provide an overview of the TEACH Program, including
      curriculum details, preliminary outcomes, barriers to continued and expanded
      implementation, and thoughts about the future of the program.

PMID- 21169778
TI  - Hypertension management in a student-run free clinic: meeting national standards?
AB  - PURPOSE: Affecting one in three adults, hypertension is one of the most prevalent
      disorders in the United States. The purpose of this analysis was to evaluate,
      using national care guidelines and quality standards, the quality of care
      provided at the Student Family Health Care Center (SFHCC) of the University of
      Medicine and Dentistry of New Jersey (Newark). METHOD: The authors performed a
      chart review of all patients seen from June 2008 to June 2009, collecting the
      following data: age, gender, ethnicity, body mass index, most recent blood
      pressure measurement, comorbid conditions, number of visits, free medications
      dispensed, and smoking status. The authors used the Joint National Committee on
      Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)
      guidelines and Healthy People 2010 quality standards to analyze results. RESULTS:
      Of the 119 SFHCC patients seen during the study period, 60 had a diagnosis of
      hypertension. Overall, 30 (50%) of these patients were at target blood pressure.
      Of the 19 patients (32% of 60) with diabetes and hypertension, 5 (26%) were
      controlled compared with 25 (61% of 41) with hypertension only. Thirty-eight
      patients (63%) were taking a thiazide, 42 (70%) were on multidrug regimens, and
      all 19 of the patients with diabetes (100%) were on an angiotensin converting
      enzyme inhibitor or angiotensin receptor blocker, as per the JNC 7 guidelines.
      CONCLUSIONS: SFHCC patients with hypertension received pharmacotherapy as
      recommended by JNC 7 guidelines and were at the blood pressure goal set by
      Healthy People 2010.

PMID- 21169779
TI  - Nonstandard Programs: the University of Pittsburgh Medical Center's next frontier
      in graduate medical education.
AB  - The University of Pittsburgh Medical Center has seen continuous growth in the
      number and types of graduate training programs not accredited by the
      Accreditation Council for Graduate Medical Education (ACGME), the American Board
      of Medical Specialties, or the American Osteopathic Association. For the purposes
      of ensuring best educational products and of controlling unrecognized competition
      with our accredited programs, a sequential process of centralized oversight of
      these nonstandard programs was undertaken. The first step involved programs whose
      fellows were hired and tracked like accredited fellows (i.e., not instructors).
      The basic process began with consensus among leadership, writing of policy with
      consultation as necessary, establishment of a registry of programs and graduates,
      and a committee to allow sharing of best practices and dissemination of policy.
      The second step applied the same process to instructor-level programs. Whereas
      the previous group of programs was made subject to ACGME regulations, more
      latitude in duty hours and progressive responsibility were allowed for instructor
      programs. The final step, in progress, is extending a similar but modified
      approach to short-duration clinical experiences and observerships. The outcomes
      of these efforts have been the creation of a centralized organizational
      structure, policies to guide this structure, an accurate registry of a surprising
      number of training programs, and a rolling record of all graduates from these
      programs. Included in the process is a mechanism that ensures that core program
      directors and department chairs specifically review the impact of new programs on
      core programs before allowing their creation.

PMID- 21169780
TI  - Understanding the goals of service learning and community-based medical
      education: a systematic review.
AB  - PURPOSE: To understand the educational goals of projects described as "service
      learning" or "community-based medical education" and to learn how relationships
      between medical schools and community members are discussed in these projects.
      METHOD: In 2008, the authors performed a systematic qualitative content analysis
      of 57 articles, published since 1990, that addressed community placements for
      U.S. medical students. After the initial analysis, the academic-based authors
      conveyed their findings to their community partner and coauthor, received input
      on relevance and priority of themes, and then refined their analysis accordingly.
      RESULTS: The authors identified five main findings: (1) Considerable
      heterogeneity existed across projects, (2) although medical schools aimed to
      improve the health of the community, they did not routinely involve community
      members in the identification of local health priorities, (3) educators were
      enthusiastic about community-based education as a method for teaching complicated
      ideas such as social determinants of health, (4) many authors emphasized
      community placements as being equivalent to traditional curricula, and (5) the
      articles did not emphasize the concept of reciprocal knowledge transfer.
      CONCLUSIONS: The authors found little emphasis on the reciprocal nature of
      partnerships between communities and medical schools. They propose that the
      principle of community partnership within medical education could train a cohort
      of medical students prepared to practice in the rapidly changing health care
      environment-one that now includes an important new agenda of community
      accountability.

PMID- 21169781
TI  - The impact of rural training experiences on medical students: a critical review.
AB  - PURPOSE: To address the growing shortage of rural physicians, several medical
      schools have developed rural training experiences for their students. However,
      little is known about the educational impact of these experiences. Thus, the
      authors conducted a critical review of North American studies examining medical
      student outcomes associated with rural training experiences. METHOD: A
      comprehensive search strategy was used to identify studies about undergraduate
      medical education in a rural setting, searching PubMed from 1966 to June 2009.
      The researchers evaluated titles and abstracts to identify publications that
      appeared to report measures associated with undergraduate medical school rural
      training experience. Only those studies with a measurable outcome such as career
      choice, practice location, clinical competency, and student satisfaction were
      analyzed. RESULTS: The review identified a total of 72 studies. Most were single
      cohort studies or cohort studies with control groups, with career choice and
      practice location the most commonly reported measure. The majority reported that
      rural experiences influenced students toward primary care specialties and to
      consider rural practice. Studies using self-report found that students generally
      valued the experience and had a high degree of satisfaction. CONCLUSIONS: This
      review shows that placement in rural settings is a positive learning experience
      that students and preceptors value. Although the evidence supports that these
      rotations influence practice site and career choice, it is not clear whether they
      reinforce preexisting interest or have the ability to motivate previously
      uninterested students to consider careers in primary care or rural medicine.

PMID- 21169782
TI  - Innovation in ambulatory care: a collaborative approach to redesigning the health
      care workplace.
AB  - PURPOSE: To improve the quality of patient care and work satisfaction of the
      physicians and staff at an ambulatory practice that had recently started an
      innovative model of clinical care for women. METHOD: The authors used an
      inclusive process, collaborative interactive action research, to engage all
      physicians and staff members in assessing and redesigning their work environment.
      Based on key barriers to working effectively and integrating work and family
      identified in that process, a pilot project with new work practices and
      structures was developed, implemented, and evaluated. RESULTS: The work redesign
      process established cross-occupational care teams in specific clinical areas.
      Members of the teams built skills in assessing clinical operations in their
      practice areas, developed new levels of collaboration, and constructed new models
      of distributed leadership. The majority of participants reported an improvement
      in how their area functioned. Integrating work and family/personal life
      particularly practices around flexible work arrangements-became an issue for team
      discussion and solutions, not a matter of individual accommodation by managers.
      CONCLUSIONS: By engaging the workforce, collaborative interactive action research
      can help achieve lasting change in the health care workplace and increase
      physicians' and staff members' work satisfaction. This "dual agenda" may be best
      achieved through a collaborative process where cross-occupational teams are
      responsible for workflow and outcomes and where the needs of patients and
      providers are integrated.

PMID- 21169783
TI  - Medical education in the Caribbean: a longitudinal study of United States Medical
      Licensing Examination performance, 2000-2009.
AB  - PURPOSE: Caribbean-educated physicians play an important role in the United
      States. The purpose of this study was to investigate medical school development
      in the Caribbean, concentrating on performance trends of Caribbean-educated
      physicians over the past decade. METHOD: The study included 26,495 Caribbean
      educated students/graduates who took one or more exams leading to Educational
      Commission for Foreign Medical Graduates (ECFMG) certification between January 1,
      2000, and December 31, 2009. The authors describe medical school development in
      the region, discuss recent student demographic trends, and summarize first
      attempt success rates, by year and country of medical school, on the United
      States Medical Licensing Examination (USMLE) Step 1 (Basic Science), Step 2
      (Clinical Knowledge [CK]) and Step 2 (Clinical Skills), or the previously
      required ECFMG Clinical Skills Assessment. RESULTS: Sixty-one medical schools
      operated in the Caribbean from 2000 to 2009, of which 56 are currently open, and
      approximately 10 new schools are in development. The number of Caribbean-educated
      ECFMG registrants has grown every year, from 1,510 in 2000 to 4,000 in 2009.
      USMLE Step 1 and Step 2 CK first-attempt pass rates generally increased over the
      study period. Performance trends by country varied widely. CONCLUSIONS: Medical
      education programs in the Caribbean and the number of Caribbean-educated ECFMG
      registrants continue to expand, with students/graduates showing performance
      improvement in some areas. Performance findings should be interpreted with
      caution, because of limitations the authors explain.

PMID- 21169784
TI  - Almost internists: analysis of students who considered internal medicine but
      chose other fields.
AB  - PURPOSE: Medical students' career choices affect health care. To understand how
      to increase the number of students who choose careers in internal medicine (IM),
      students who seriously considered IM but chose another field ("Switchers") and
      those who rejected IM ("Never Considered") were compared with those who chose IM
      ("Choosers"). METHOD: Fourth-year medical students from 11 U.S. institutions were
      surveyed about demographics, medical school educational experiences, and aspects
      of the specialty of IM. Univariate analysis and multivariate logistic regression
      models examined associations between student characteristics and classification
      as Switchers, Choosers, and Never Considered. RESULTS: A total of 1,177 students
      completed the survey (82% response rate). There were 274 (23%) Choosers, 398
      (34%) Switchers, and 499 (43%) Never Considered. The authors' models explained
      over 80% of variance in these three career choice classification groups. For most
      responses, an increasingly favorable gradient from Never Considered to Choosers
      was observed. Multivariate analysis revealed six items that were associated with
      higher probability of choosing IM: types of patients internists see, timing of
      career decision, interest groups, intellectual challenge, satisfaction among
      internists, and the core IM clerkship. CONCLUSIONS: Several potentially
      modifiable educational experiences and aspects of IM distinguished Switchers from
      the other two groups. The percentage of variance explained by group suggests that
      these findings identify important underpinnings of career decisions. These items
      also suggest ways that educational experiences and aspects of the specialty could
      be redesigned by academicians and policy makers to improve the attractiveness of
      IM careers.

PMID- 21169785
TI  - Effect of financial remuneration on specialty choice of fourth-year U.S. medical
      students.
AB  - PURPOSE: To investigate whether financial incentives could reverse the trend of
      declining interest in primary care specialties among U.S. medical students.
      METHOD: An electronic survey was sent to all U.S. fourth-year MD and DO medical
      students in 2009 with a Department of Defense service obligation. Students not
      selecting a primary care residency were asked if a hypothetical bonus paid before
      and after residency or an increase in annual salary of attendings in primary care
      specialties would have resulted in these students selecting primary care.
      Logistic regression was used to determine student characteristics associated with
      accepting a financial incentive. RESULTS: The survey response rate was 56%
      (447/797). Sixty-six percent of students did not apply for a primary care
      residency. Of these, 30% would have applied for primary care if they had been
      given a median bonus of $27,500 (interquartile range [IQR] $15,000-$50,000)
      before and after residency. Forty-one percent of students would have considered
      applying for primary care for a median military annual salary after residency of
      $175,000 (IQR $150,000-$200,000). Students who considered primary care but chose
      a controllable lifestyle specialty (e.g., radiology) were nearly four times more
      likely to name an influential hypothetical salary than were students who did not
      consider primary care and chose a noncontrollable lifestyle specialty (e.g.,
      surgery) (67% versus 17%, P < .0001). CONCLUSIONS: U.S. medical students,
      particularly those considering primary care but selecting controllable lifestyle
      specialties, are more likely to consider applying for a primary care specialty if
      provided a financial incentive.

PMID- 21169786
TI  - Characteristics of medical school matriculants who participated in
      postbaccalaureate premedical programs.
AB  - PURPOSE: To identify factors associated with U.S. medical school matriculants'
      postbaccalaureate premedical program participation and to determine whether
      participation was associated with plans at medical school graduation to practice
      in underserved areas. METHOD: Deidentified, individualized records of Association
      of American Medical Colleges (AAMC) Matriculating Student Questionnaire responses
      for the 1996- 2000 cohort of U.S. medical school matriculants were analyzed using
      multivariable logistic regression for associations with postbaccalaureate
      premedical program participation. Postbaccalaureate premedical program
      participation was analyzed for associations with plans at medical school
      graduation to practice in underserved areas. Adjusted odds ratios (ORs)
      significant at P < .05 are reported for independent predictors of
      postbaccalaureate program participation among matriculants and of graduates'
      plans to practice in underserved areas. RESULTS: The sample of 57,276
      matriculants included 3,561 (6.2%) academic record enhancer (ARE), 3,931 (6.9%)
      career changer (CC), and 1,354 (2.4%) career changer/academic record enhancer
      program participants (ARE/CC). Matriculants who participated in summer academic
      enrichment programs (OR = 1.35), had premedical debt (OR = 1.25), and were
      underrepresented minorities (OR = 1.21) were more likely to report ARE
      participation. Women (OR = 1.46) were more likely to report CC participation.
      Compared with nonparticipants, ARE, CC, and ARE/CC participants were each more
      likely to plan, at medical school graduation, to practice in underserved areas
      (OR = 1.14, 1.48, and 1.47, respectively). CONCLUSIONS: Among medical school
      matriculants, postbaccalaureate premedical program participants were
      demographically diverse and, at medical school graduation, were more likely than
      nonparticipants to plan to practice in underserved areas.

PMID- 21169787
TI  - Support for investigator-initiated clinical research involving investigational
      drugs or devices: the Clinical and Translational Science Award experience.
AB  - PURPOSE: Investigator-initiated research involving investigational drugs and
      devices is key to improving health. However, this requires the investigator to
      serve as a "sponsor-investigator," which can be complex and overwhelming. The
      Investigational New Drug/Investigational Device Exemption (IND/IDE) Taskforce of
      the Clinical and Translational Science Award (CTSA) consortium carried out a
      survey to examine how academic health centers (AHCs) assist sponsor-investigators
      with regulatory responsibilities. METHOD: The 24 CTSA centers existing in 2008
      were surveyed regarding regulatory oversight and support for sponsor
      investigators. Responses were analyzed by descriptive statistics. The evaluation
      of survey responses yielded three models of institutional support/oversight.
      RESULTS: Nineteen centers and one affiliate responded. Eleven (55%) reported
      having an IND/IDE support office, increased from five (25%) prior to their CTSA
      award. The volume of investigator-initiated IND/IDE research was highly variable
      (measured by numbers of investigators, IND/IDE applications, and studies).
      Oversight, if done, was provided by either the IND/IDE office or elsewhere in the
      institution. Most IND/IDE offices assisted with IND/IDE submissions and
      preparation for external audits. Half reported advanced training for sponsor
      investigators. Almost all reported a goal to increase IND/IDE research. Important
      issues include the need for robust training of investigator/staff, appropriate
      determination of IND-exempt research, and sufficient support for preparing
      IND/IDE applications. CONCLUSIONS: Investigator-initiated research involving
      IND/IDEs is essential, but complex. AHCs should examine how they support sponsor
      investigators in meeting the complex requirements. A model of either expert
      consultation/support or full service will minimize risks to participants and
      institutions, and regulatory noncompliance.

PMID- 21169788
TI  - Perspective: Competencies, outcomes, and controversy--linking professional
      activities to competencies to improve resident education and practice.
AB  - Regulatory organizations have recently emphasized the importance of structuring
      graduate medical education around mastery of core competencies. The difficulty is
      that core competencies attempt to distill a range of professional behaviors into
      arguable abstractions. As such, competencies can be difficult to grasp for
      trainees and faculty, who see them as unrelated to the intricacies of daily
      patient care. In this article, the authors describe how two initiatives are
      converging in a way that should make competencies tangible and relevant. One
      initiative is based on the idea that competencies will be more meaningful if
      trainees understand specifically how they relate to important professional
      activities in their own specialty. The authors suggest that there is a dyadic
      relationship between competencies and major professional activities in pediatric
      medicine. They also suggest that these relationships should be discussed as part
      of the process by which trainees are entrusted to perform clinical activities
      without direct supervision. The other initiative proposes to construct narrative
      milestones that provide a picture of what progression toward mastery of core
      competencies might look like. Together, the authors argue, these two initiatives
      should illuminate the core competencies by providing relevant clinical context
      and valuable educational substance.

PMID- 21169790
TI  - Case scenario: Management of intraoperative hypoxemia during one-lung
      ventilation.

PMID- 21169792
TI  - Burnout and the relative value of dopamine.

PMID- 21169791
TI  - Isoflurane neurotoxicity is mediated by p75NTR-RhoA activation and actin
      depolymerization.
AB  - BACKGROUND: The mechanisms by which isoflurane injured the developing brain are
      not clear. Recent work has demonstrated that it is mediated in part by activation
      of p75 neurotrophin receptor. This receptor activates RhoA, a small guanosine
      triphosphatase that can depolymerize actin. It is therefore conceivable that
      inhibition of RhoA or prevention of cytoskeletal depolymerization might attenuate
      isoflurane neurotoxicity. This study was conducted to test these hypotheses using
      primary cultured neurons and hippocampal slice cultures from neonatal mouse pups.
      METHODS: Primary neuron cultures (days in vitro, 4-7) and hippocampal slice
      cultures from postnatal day 4-7 mice were exposed to 1.4% isoflurane (4 h).
      Neurons were pretreated with TAT-Pep5, an intracellular inhibitor of p75
      neurotrophin receptor, the cytoskeletal stabilizer jasplakinolide, or their
      corresponding vehicles. Hippocampal slice cultures were pretreated with TAT-Pep5
      before isoflurane exposure. RhoA activation was evaluated by immunoblot.
      Cytoskeletal depolymerization and apoptosis were evaluated with
      immunofluorescence microscopy using drebrin and cleaved caspase-3 staining,
      respectively. RESULTS: RhoA activation was increased after 30 and 120 min of
      isoflurane exposure in neurons; TAT-Pep5 (10 MUm) decreased isoflurane-mediated
      RhoA activation at both time intervals. Isoflurane decreased drebrin
      immunofluorescence and enhanced cleaved caspase-3 in neurons, effects that were
      attenuated by pretreatment with either jasplakinolide (1 MUm) or TAT-Pep5. TAT
      Pep5 attenuated the isoflurane-mediated decrease in phalloidin
      immunofluorescence. TAT-Pep5 significantly attenuated isoflurane-mediated loss of
      drebrin immunofluorescence in hippocampal slices. CONCLUSIONS: Isoflurane results
      in RhoA activation, cytoskeletal depolymerization, and apoptosis. Inhibition of
      RhoA activation or prevention of downstream actin depolymerization significantly
      attenuated isoflurane-mediated neurotoxicity in developing neurons.

PMID- 21169793
TI  - p38 Mitogen-activated protein kinase activation by nerve growth factor in primary
      sensory neurons upregulates MU-opioid receptors to enhance opioid responsiveness
      toward better pain control.
AB  - BACKGROUND: Sensory neuron opioid receptors are targets for spinal, epidural, and
      peripheral opioid application. Although local nerve growth factor (NGF) has been
      identified as a mediator of sensory neuron MU-opioid receptor (MOR) up
      regulation, the signaling pathways involved have not been yet identified.
      METHODS: Wistar rats were treated with intraplantar vehicle, Freund's complete
      adjuvant, NGF, NGF plus intrathecal p38 mitogen-activated protein kinase (MAPK)
      inhibitors, or NGF plus extracellular signal-regulated kinase-1/2 MAPK
      inhibitors. After 4 days of treatment, paw pressure thresholds of an intraplantar
      full (fentanyl) or partial (buprenorphine) opioid agonist were determined by
      algesiometry. Tissue samples from rat dorsal root ganglia were subjected to
      radiolabeled ligand binding, Western blot analysis, and confocal
      immunofluorescence. RESULTS: Exogenous and endogenous NGF resulting from Freund's
      complete adjuvant inflammation produced significant potentiation and enhanced
      efficacy in fentanyl- and buprenorphine-induced dose-dependent antinociception,
      respectively. Furthermore, in the ipsilateral dorsal root ganglia, NGF produced a
      significant increase in MOR binding sites, proteins, and immunoreactive neurons.
      In parallel, phosphorylated p38-MAPK protein, the number of phosphorylated p38
      MAPK immunoreactive neurons expressing MOR in dorsal root ganglia, and the
      peripherally directed axonal transport of MOR significantly increased. Finally,
      NGF-induced effects occurring in dorsal root ganglia, on axonal transport, and on
      the potentiation or enhanced efficacy of opioid antinociception were abrogated by
      inhibition of p38, but not extracellular signal-regulated kinase-1/2, MAPK.
      CONCLUSIONS: Local NGF through activation of the p38-MAPK pathway leads to
      adaptive changes in sensory neuron MOR toward enhanced susceptibility to local
      opioids. This effect may act as a counter-regulatory response to p38-MAPK-induced
      pain (e.g., inflammatory pain) to facilitate opioid-mediated antinociception.

PMID- 21169794
TI  - Evaluation of a new routine diagnostic test for immunoglobulin E sensitization to
      neuromuscular blocking agents.
AB  - BACKGROUND: Neuromuscular blocking agents (NMBA) are responsible for most
      immediate hypersensitivity reactions during anesthesia, as a result of the
      presence of a quaternary ammonium ion. The aim of this study was to evaluate the
      diagnostic performance of a commercial immunoglobulin E (IgE) test (quaternary
      ammonium morphine [QAM]) for diagnosing sensitivity to NMBA. METHODS: We tested
      168 patients exposed to NMBAs during anesthesia. Of those patients, 54 had an
      uneventful procedure and 114 had immediate hypersensitivity reactions, and 57
      patients had positive skin tests to the administered NMBA, whereas 57 had
      negative skin tests. Specific IgE concentrations determined with the QAM method
      based on a morphine solid phase were compared with those obtained with a
      recommended experimental method with a choline solid phase. RESULTS: For the QAM
      test, a 0.35 kUA/l positivity cutoff was chosen from the receiver operating
      characteristics curve. QAM-specific IgE was found in 84.2% of skin test-positive
      reactors (80.7% with the recommended method; no significant difference), and
      binding was inhibited by the culprit NMBA in 80% of cases. The frequency of QAM
      specific IgE positivity was significantly higher in skin test-negative reactors
      (24.6%) than in controls (9.3%), suggesting NMBA sensitivity. CONCLUSION:
      Sensitivity of the QAM test (84.2%), together with its simplicity and suitability
      for routine laboratory use, makes it a valuable tool, in conjunction with skin
      tests, for diagnosing NMBA sensitivity in patients who react after NMBA
      injection. The QAM test is of particular interest when skin tests are not
      available or not reliable or give results poorly compatible with mediator release
      or clinical features.

PMID- 21169795
TI  - Impaired visual hand recognition in preoperative patients during brachial plexus
      anesthesia: importance of peripheral neural input for mental representation of
      the hand.
AB  - BACKGROUND: Perceptual illusions described in healthy subjects undergoing
      regional anesthesia (RA) are probably related to short-term plastic brain
      changes. We addressed whether performance on an implicit mental rotation task
      reflects these RA-induced changes in body schema brain representations. Studying
      these changes in healthy volunteers may shed light on normal function and the
      central mechanisms of pain. METHODS: Performance pattern was studied in upper
      limb-anesthetized subjects on a left/right hand judgment task, which is known to
      involve motor imagery processes relating to hand posture. Three conditions were
      used: control (i.e., absence of deafferentation), RA (i.e., deafferentation), and
      vision (i.e., deafferentated limb exposed to view). To limit potential bias such
      as order effect, the control state was recorded in a randomized manner. RESULTS:
      All subjects described perceptual illusions of their anesthetized limb. They were
      slower and less accurate on the task during RA compared with control. Response
      patterns were similar in all conditions, suggesting sensitivity of performance to
      arm/hand biomechanical constraints. Vision was associated with an increase in the
      proportion of correct responses and a reduction of the response times in hand
      judgment and was accompanied by disappearance of the lateralization of the
      underlying mental representations, which was identified during RA. CONCLUSIONS:
      These results suggest the following: (1) the right/left judgment task involves
      mental simulation of hand movements, (2) underlying mental representations and
      their neural substrates are subject to acute alterations after RA, and (3) the
      proprioceptive deficit induced by RA is influenced by the subject's ability to
      see the anesthetized limb.

PMID- 21169796
TI  - Prevalence of malignant hyperthermia and relationship with anesthetics in Japan:
      data from the diagnosis procedure combination database.
AB  - BACKGROUND: Malignant hyperthermia (MH) is a rare but life-threatening disease
      that occurs during general anesthesia. The actual prevalence of MH remains
      unclear, and the association between MH and various anesthetic drugs remains
      controversial because of a lack of universal reporting. METHODS: Using the
      Japanese Diagnosis Procedure Combination database, we collected data of
      inpatients who had general anesthesia between July and December 2006-2008.
      Patients' age, gender, diagnoses, procedures, and the use of drugs during
      anesthesia, including volatile agents, muscle relaxants, and propofol, were
      investigated. Univariate comparisons were made to examine the relationship of
      each anesthetic drug or demographic factor with the occurrence of MH. RESULTS: Of
      1,238,171 surgical patients undergoing general anesthesia, we identified 17 MH
      patients. Only one in-hospital death was identified. Men were significantly more
      likely to contract MH(odds ratio: 3.49; 95% CI 1.14 -10.7; P=0.029). No MH
      patient was found among 19,871 suxamethonium users. The prevalence of MH was
      relatively high in users of sevoflurane and rocuronium compared with nonusers but
      was not statistically significant [corrected].. CONCLUSIONS: No single drug was
      significantly associated with the occurrence of MH. Data should be continuously
      compiled, and further analyses with larger numbers of cases are necessary to
      identify possible causative agents.

PMID- 21169797
TI  - Prolonged suppression of postincisional pain by a slow-release formulation of
      lidocaine.
AB  - BACKGROUND: Postoperative pain can occur despite nerve blocks during the surgical
      period. Here we tested Xybrex (Orthocon, Inc., Irvington, NY), a slow-release
      formulation of lidocaine that blocks rat sciatic nerve for 1-2 days, for its
      ability to suppress postincisional pain. METHODS: A plantar paw incision was made
      in rats, either along the midline (Brennan model) or at the lateral edge, 30 min
      after different treatment groups received either lidocaine (0.2 ml, 2%) or Xybrex
      implant at the ipsilateral sciatic nerve or Xybrex at the contralateral sciatic
      nerve. Behavioral testing by von Frey filaments occurred at 2 and 6 h
      postoperatively and for the next 10 postoperative days. The fractional response
      (paw withdrawal responses per 10 pokes) was scored at each time. RESULTS:
      Mechanosensitivity from the Brennan paw incision was reduced throughout the
      postoperative period by ipsilateral Xybrex, although lidocaine injection almost
      had no effect. Contralateral Xybrex had a weaker but still significant
      antihyperalgesic effect, converging to that from ipsilateral Xybrex at
      postoperative day 2. Xybrex at the nuchal midline reduced allodynia for only
      postoperative days 1-3, whereas hyperalgesia was reduced continuously after
      postoperative day 2. Hyperalgesia from the lateral incision was also reduced by
      ipsilateral Xybrex but not by contralateral Xybrex. CONCLUSIONS: Implants of slow
      release lidocaine formulations are most effective against postincisional pain
      when placed at the ipsilateral nerve innervating the area of incision.
      Contralateral nerve implants are somewhat less effective, probably acting by
      releasing lidocaine into the systemic circulation. There appears to be a
      differential role of central sensitization between postincisional allodynia and
      hyperalgesia.

PMID- 21169798
TI  - Anesthetic preconditioning: an anesthesiologist's tale. 1997.

PMID- 21169799
TI  - Protein kinase A-dependent spinal alpha-amino-3-hydroxy-5-methyl-4
      isoxazoleproprionate-receptor trafficking mediates capsaicin-induced colon
      urethra cross-organ reflex sensitization.
AB  - BACKGROUND: Intracellular redistribution of alpha-amino-3-hydroxy-5-methyl-4
      isoxazoleproprionate receptors (AMPARs) is known to be induced by natural painful
      stimulation. We tested the hypothesis that that protein kinase A (PKA)-dependent
      AMPAR trafficking underlies the development of N-methyl-d-aspartate receptor
      mediated cross-organ sensitization in vivo. METHODS: We recorded urethra reflex
      activity and analyzed immunoblotting of lumbosacral (L6-S2) dorsal horn (DH)
      tissue obtained from animal preparations after intrathecal 8-bromo-cyclic
      adenosine monophosphate injection or intracolonic instillation with 8-methyl-N
      vanillyl-trans-6-nonenamide (capsaicin). RESULTS: Intrathecal 8-bromo-cyclic
      adenosine monophosphate (300 MUM, 10 MUl) induced reflex potentiation (81.85 +/-
      22.21 spikes/stimulation) and increased the number of AMPAR Glu receptor 1
      subunits in the membrane fraction of DH (1.8-fold increase vs. control). This
      process was prevented by pretreatment with the PKA inhibitor N-[2- ((p
      bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide(10 MUM, 10 MUl, 2.7 +/- 0.8
      [mean +/- SE] spikes/stimulation) and human thyroid A kinase-anchoring protein
      (10 MUM, 10 MUl, 11.5 +/- 4.8 spikes/stimulation), an inhibitor of PKA and PKA-A
      kinase-anchoring protein interactions. Intracolonic capsaicin instillation
      sensitized the urethra reflex (137.2 +/- 62.4 spikes/stimulation) and, relative
      to control, simultaneously provoked an increase (2.9-fold) in the membrane
      fraction and a decrease (0.9-fold) in the cytosolic fraction of Glu receptor 1
      subunits in DH. Inhibition of PKA activity and disruption of PKA-A kinase
      anchoring protein interaction in the DH (2.0 +/- 0.6 and 16.7 +/- 2.8
      spikes/stimulation, respectively) are sufficient to prevent capsaicin-dependent
      reflex sensitization and AMPAR trafficking in the membrane fraction (0.6- and 0.5
      fold increase capsaicin). CONCLUSION: Delivery of AMPAR-containing Glu receptor 1
      subunits to the membranes of lumbosacral DH neurons through a PKA-dependent
      pathway contributes to noxious stimulation-induced synaptic strengthening, which
      plays roles in colon-urethra reflex sensitization.

PMID- 21169800
TI  - Ideal permissive hypotension to resuscitate uncontrolled hemorrhagic shock and
      the tolerance time in rats.
AB  - BACKGROUND: Studies have shown that permissive hypotension for uncontrolled
      hemorrhagic shock can result in good resuscitation outcome. The ideal target mean
      arterial pressure (MAP) and the tolerance time for permissive hypotension have
      not been determined. METHODS: To elucidate the ideal target MAP and tolerance
      time for permissive hypotension with uncontrolled hemorrhagic shock rats, the
      effects of different target MAPs (40, 50, 60, 70, 80, and 100 mmHg) and 60-, 90-,
      and 120-min permissive hypotension (50 mmHg) on uncontrolled hemorrhagic shock
      were observed. RESULTS: Rats in normotensive groups (80 and 100 mmHg) had
      increased blood loss (101%, 126% of total blood volume), decreased hematocrit,
      decreased vital organ (liver and kidney) and mitochondrial function, and
      decreased animal survival rate (1 of 10). Rats in the 50- and 60-mmHg target MAP
      groups had decreased blood loss (52% and 69%, respectively), good hematocrit and
      vital organ and mitochondrial function, stable hemodynamics, and increased animal
      survival (8 of 10 and 6 of 10, respectively). Rats in the 40-mmHg target MAP
      group, although having decreased blood loss (39%), appeared to have very inferior
      organ function and animal survival (2 of 10). Animal survival (1 of 10) and vital
      organ function in the 120-min permissive hypotension group were significantly
      inferior to the 60- and 90-min groups. The 60- and 90-min groups had similar
      animal survival (8 of 10 and 6 of 10) and vital organ function. CONCLUSION: A
      target resuscitation pressure of 50-60 mmHg is the ideal blood pressure for
      uncontrolled hemorrhagic shock. Ninety minutes of permissive hypotension is the
      tolerance limit; 120 min of hypotensive resuscitation can cause severe organ
      damage and should be avoided.

PMID- 21169801
TI  - Hypernatremia-induced limbic system damage.

PMID- 21169802
TI  - Preparation of modern anesthesia workstations for malignant hyperthermia
      susceptible patients: a review of past and present practice.
AB  - Patients with malignant hyperthermia experience an exaggerated metabolic response
      when exposed to volatile anesthetic gases and succinylcholine. The minimum
      concentration of anesthetic gas needed to trigger a malignant hyperthermia crisis
      in humans is unknown and may remain so because of the inherent risks associated
      with studying the complex nature of this rare and lethal genetic disorder. The
      Malignant Hyperthermia Association of the United States provides specific
      instructions on purging anesthesia machines of volatile agents to reduce the risk
      of exposure. However, these recommendations were developed from studies of older
      generation machines. Modern anesthesia workstations are more complex and contain
      more gas absorbing materials. A review of the literature found the current
      guidelines inadequate to prepare newer generation workstations, which require
      more time for purging anesthetic gases, autoclaving or replacement of parts, and
      modifications to the gas delivery system. Protocols must be developed to prepare
      newer generation anesthesia machines.

PMID- 21169803
TI  - Unanticipated difficult airway management in the prehospital emergency setting:
      prospective validation of an algorithm.
AB  - BACKGROUND: Difficult intubation management algorithms have proven efficacy in
      operating rooms but have rarely been assessed in a prehospital emergency setting.
      We undertook a prospective evaluation of a simple prehospital difficult
      intubation algorithm. METHODS: All of our prehospital emergency physicians and
      nurse anesthetists were asked to adhere to a simple algorithm in all cases of
      impossible laryngoscope-assisted tracheal intubation. They received a short
      refresher course and training in the use of the gum elastic bougie (GEB) and the
      intubating laryngeal mask airway (ILMA), which were techniques to be used as a
      first and a second step, respectively. In cases of difficult ventilation with
      arterial desaturation, IMLA was to be used first. Cricothyroidotomy was the
      ultimate rescue technique when ventilation through ILMA failed. Patient
      characteristics, adherence to the algorithm, management efficacy, and early
      complications were recorded (August 2005-December 2009). RESULTS: An alternative
      technique to secure the airway was needed in 160 of 2,674 (6%) patients
      undergoing intubation. Three instances of nonadherence to the algorithm were
      recorded. GEB was used first in 152 patients and was successful in 115. ILMA was
      used first in 8 patients and second in the 37 GEB-assisted intubation failures.
      Forty-five patients were successfully mask-ventilated, and 42 were blindly
      intubated before reaching the hospital. Cricothyroidotomy was used successfully
      in a patient with severe upper airway obstruction as a result of pharyngeal
      neoplasia. Early intubation-related complications occurred in 52% difficult
      cases. CONCLUSION: Adherence to a simple algorithm using GEB, ILMA, and
      cricothyroidotomy solved all difficult intubation cases occurring in a
      prehospital emergency setting.

PMID- 21169804
TI  - Continuous measurement of blood glucose: validation of a new intravascular
      sensor.
AB  - BACKGROUND: Tight blood glucose control is used extensively in perioperative and
      critically ill patients. Several studies, however, have shown contradictory
      effects on patient outcomes. A major problem of these studies has been inadequate
      control of the prime variable, blood glucose. This paper describes the validation
      of a new intravascular continuous blood glucose sensor. METHODS: The glucose
      sensor was placed in the superior caval vein of seven anesthetized pigs. Sensor
      readings were compared with arterial blood gas readings. Fluctuations in blood
      glucose were created using intravenous glucose and insulin. A total of 807 paired
      sensor and blood gas readings were obtained. RESULTS: The sensor was tested with
      a range of blood glucose values (0.63-15.75 mM [mean bias, 0.0131 mM]). Analysis
      using Bland-Altman plots yielded 95% limits of agreement at -0.908 and 0.934 mM.
      There were 121 paired measurements with a mean value below 2.2 mM, yielding 95%
      limits of agreement at -0.553 and 0.466 mM. CONCLUSIONS: The performance of the
      sensor was in agreement with blood gas measurements in a wide range of glucose
      values. For the clinician, it is noteworthy that performance was equally good in
      the hypoglycemic area.

PMID- 21169805
TI  - Perioperative reductions in circulating lymphocyte levels predict wound
      complications after excisional breast cancer surgery.
AB  - OBJECTIVE: Postoperative wound complications after excisional surgery for primary
      breast cancer can result in patients requiring additional treatments and delay
      adjuvant therapy and are associated with worse prognoses.We investigated factors
      that might predispose patients to wound complications. BACKGROUND: A number of
      patient characteristics have been associated with wound complications, but there
      is currently no quantitative measure of the risk of their occurrence. Our
      hypothesis was that wound complications are related, in part, to the immune
      status of patients. METHODS: We recruited patients undergoing surgery for primary
      breast cancer and determined their circulating levels of various immune cells
      shortly before and after surgery as a measure of immune status. RESULTS: One
      hundred seventeen patients were recruited; 16 (13.7%) developed wound
      complications. The following patient and tumor characteristics were associated
      with higher wound complication rates: diabetes (P = 0.02); larger tumors (T2/3 vs
      T1; P = 0.02); metastatic axillary nodes (P = 0.006). With respect to immune
      status, no significant differences in preoperative levels of circulating immune
      cells were detected between patients who developed wound complications and those
      who did not. However, patients who developed complications showed greater
      reductions in lymphocyte levels 4 hours postoperatively than those who did not (P
      <0.001). Multivariate analyses demonstrated that falls in lymphocyte levels of
      greater than 20% or 50% 4 hours postoperatively acted as a significant and
      independent predictor of wound complications (P < 0.005 and P <
      0.0001,respectively). CONCLUSIONS: Perioperative changes in lymphocyte levels
      could provide a practical predictive marker for wound complications on which
      selective antibiotic prophylaxis could be based.

PMID- 21169806
TI  - Esophageal dysmotility disorders after laparoscopic gastric banding--an
      underestimated complication.
AB  - OBJECTIVE: To evaluate the effects of laparoscopic adjustable gastric banding
      (LAGB) on esophageal dysfunction over the long term in a prospective study, based
      on a 12-year experience. BACKGROUND: Esophageal motility disorders and dilatation
      after LAGB have been reported. However, only a few studies present long-term
      follow-up data. METHODS: Between June 1998 and June 2009, all patients with
      implantation of a LAGB were enrolled in a prospective clinical trial including a
      yearly barium swallow. Esophageal motility disorders were recorded and classified
      over the period. An esophageal diameter of 35 mm or greater was considered
      dilated. RESULTS: Laparoscopic adjustable gastric banding was performed in 167
      patients (120 females and 47 males) with a mean age of 40.1+/-5.2 years. Overall
      patient follow-up was 94%. Esophageal dysmotility disorders were found in 108
      patients (68.8% of patients followed). Esophageal dilatation occurred in 40
      patients (25.5%)with a mean esophageal diameter of 47.3+/-6.9 mm(35.0-94.6) after
      a follow-up of 73.8 +/- 6.8 months (36-120) compared with 26.2+/- 2.8 mm (18.3
      34.2) in patients without dilatation (diameter of <35 mm)(P < 0.01). Thirty-four
      patients suffered from stage III dilatation (band deflation necessary) and 6 from
      stage IV (major achalasia-like dilatation, band removal mandatory). In 29
      patients, upper endoscopy was carried out because of heartburn/dysphagia. In 18
      patients, the endoscopy was normal; 9 patients suffered from gastroesophageal
      reflux disease, 1 from a stenosis, and 1 from a hiatus hernia. CONCLUSIONS: This
      study demonstrates that esophageal motility disorders after LAGB are frequent,
      poorly appreciated complications. Despite adequate excess weight loss, LAGB
      should probably not be considered the procedure of first choice and should be
      performed only in selected cases until reliable criteria for patients with a low
      risk for the procedure's long-term complications are developed.

PMID- 21169807
TI  - Prognostic value of endoscopic biopsy findings after induction chemoradiotherapy
      with and without surgery for esophageal cancer.
AB  - OBJECTIVE: To investigate the value of endoscopic biopsy in predicting the
      clinicopathological response and survival in patients with esophageal cancers who
      received chemoradiotherapy (CRT) alone or CRT followed by surgery. BACKGROUND:
      Endoscopic biopsy examination after CRT for esophageal cancer has been used to
      confirm the presence of residual tumor before surgery, but there is little or no
      information on the clinical significance of the results of endoscopic biopsy in
      neoadjuvant or definitive CRT. METHODS: We studied 189 patients who underwent
      endoscopic biopsy after induction CRT (40 Gy) for esophageal cancer, consisting
      of 123 patients who received neoadjuvant CRT (40 Gy) followed by surgery and 66
      patients who underwent definitive CRT (mostly more than 60 Gy). The correlations
      between the results of endoscopic biopsy and clinicopathological factors,
      including response to CRT and survival, were examined. RESULTS: For neoadjuvant
      CRT, endoscopic biopsy findings correlated significantly with pathological tumor
      regression and lymph node involvement,although the majority of cases with
      negative biopsy (64%) displayed residual tumor cells in the surgical specimen.
      The 5-year survival rate was significantly higher in patients with negative
      biopsy (48.3%) than in those with positive biopsy (21.8%, P = 0.006). For
      definitive CRT, patients with negative biopsy at the time of 40 Gy showed
      clinical complete response to CRT (P = 0.002)and had significantly better 3-year
      survival (57.0%) than those with positive biopsy (22.5%, P = 0.0008).
      CONCLUSIONS: The results of endoscopic biopsy examination after induction CRT can
      predict the response to CRT and prognosis of patients who receive CRT with and
      without surgery.

PMID- 21169808
TI  - A predictive model for lymph node yield in colon cancer resection specimens.
AB  - OBJECTIVE: To develop a predictive model of lymph node yield in a series of colon
      cancer resection specimens with detailed anatomic and surgical technique data.
      BACKGROUND: Lymph node yield in colon resection specimens has been associated
      with accuracy of staging and cancer outcomes. We hypothesized that lymph node
      yield is associated with multiple factors including patient, tumor,and surgical
      variables. METHODS: The pathology specimens from 152 elective colon neoplasm
      resections were prepared so that the lymph nodes were separated according to
      their anatomic relationship to the vascular pedicles and to the tumor. Prior to
      dissection, the specimen was measured. A linear regression analysis of a priori
      identified predictors and confounders of lymph node quantity was performed.
      Potential predictors in the model were age, gender, tumor stage, size,
      location,and differentiation, presence of lymphovascular or perineural
      invasion,mucinous histology, number of vascular pedicles, and use of endoscopic
      tattoo. Potential confounders were American Society of Anesthesiologists class,
      body mass index, count of lymph node metastasis, and specimen length. RESULTS:
      Tumor size, tumor location, number of resected pedicles, and use of tattoo had a
      significant linear or quadratic relationship with lymph node yield when
      controlling other variables. 23% of the variation in lymph node count was
      explained by the 15 variables in the model. A model with the 4 significant
      variables explained 19% of the variation. CONCLUSION: Multiple tumor and surgical
      factors are associated with lymph node yields in colon specimens. A standard
      minimum of lymph nodes may not be applicable to all colon cancer resections.

PMID- 21169809
TI  - Selective reduction in neural responses to high calorie foods following gastric
      bypass surgery.
AB  - OBJECTIVE: To investigate changes in neural activation and desire to eat in
      response to appetitive cues from pre- to postbariatric surgery for obesity.
      BACKGROUND: Roux-en-Y gastric bypass (RYGB) is the most common bariatric
      procedure. However, the mechanisms of action in RYGB are not well understood. A
      significant proportion of the resulting reduction in caloric intake is
      unaccounted for by the restrictive and malabsorptive mechanisms and is thought to
      be mediated by neuroendocrine function. Numerous investigations of postsurgical
      changes in gut peptides have resulted; however, changes in neural activation
      after RYGB surgery have not been previously investigated. METHODS: Functional
      magnetic resonance imaging and verbal rating scales were used to assess brain
      activation and desire to eat in response to high- and low-calorie food cues in 10
      female patients 1-month pre- and post-RYGB surgery. RESULTS: Postsurgical
      reductions in brain activation were found in key areas within the mesolimbic
      reward pathway, which were significantly more pronounced in response to food cues
      that were high (vs. low) in caloric density. These changes mirrored concurrent
      postsurgical reductions in desire to eat, which were also greater in response to
      food cues that were high versus low in caloric density (P = 0.007). CONCLUSIONS:
      Findings support the contention that RYGB surgery leads to substantial changes in
      neural responses to food cues encountered in the environment, provide a potential
      mechanism for the selective reduction in preferences for high-calorie foods, and
      suggest partial neural mediation of changes in caloric intake seen after RYGB
      surgery.

PMID- 21169810
TI  - Linking transgene expression of engineered mesenchymal stem cells and
      angiopoietin-1-induced differentiation to target cancer angiogenesis.
AB  - OBJECTIVE: To specifically target tumor angiogenesis by linking transgene
      expression of engineered mesenchymal stem cells to angiopoietin-1-induced
      differentiation. BACKGROUND: Mesenchymal stem cells (MSCs) have been used to
      deliver therapeutic genes into solid tumors. These strategies rely on their
      homing mechanisms only to deliver the therapeutic agent. METHODS: We engineered
      murine MSC to express reporter genes or therapeutic genes under the selective
      control of the Tie2 promoter/enhancer. This approach uses the differentiative
      potential of MSCs induced by the tumor microenvironment to drive therapeutic gene
      expression only in the context of angiogenesis. RESULTS: When injected into the
      peripheral circulation of mice with either, orthotopic pancreatic or spontaneous
      breast cancer, the engineered MSCs were actively recruited to growing tumor
      vasculature and induced the selective expression of either reporter red
      florescent protein or suicide genes [herpes simplex virus-thymidine kinase (TK)
      gene] when the adoptively transferred MSC developed endothelial-like
      characteristics. The TK gene product in combination with the prodrug ganciclovir
      (GCV) produces a potent toxin, which affects replicative cells. The homing of
      engineered MSC with selective induction of TK in concert with GCV resulted in a
      toxic tumor-specific environment. The efficacy of this approach was demonstrated
      by significant reduction in primary tumor growth and prolongation of life in both
      tumor models. CONCLUSION: This "Trojan Horse" combined stem cell/gene therapy
      represents a novel treatment strategy for tailored therapy of solid tumors.

PMID- 21169811
TI  - Optimizing surgical care of colon cancer in the older adult population.
AB  - OBJECTIVE: We have undertaken the current study to evaluate factors that
      correlate with postoperative complications in older patients undergoing surgery
      for colon cancer. PATIENTS AND METHODS: The database of the American College of
      Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) from years
      2005 to 2008 was accessed. Patients age 65 and older were included according to
      Current Procedural Terminology and International Classification of Disease-9
      codes. Preoperative and operative variables were examined and postoperative
      complications assessed using a combination of univariate and multivariate
      statistical models. Propensity score matching was used to control for
      nonrandomization of the database. RESULTS: We found that patients undergoing
      laparoscopic (n = 2113) and open (n = 3801) surgery for the diagnosis of colon
      cancer were similar in age and gender. However, patients undergoing laparoscopic
      surgery were generally at lower risk for developing postoperative complications
      (16.1% vs. 25.4%, P < 0.005). Statistical models controlling for preoperative and
      operative variables demonstrated patients with elevated body mass index (odds
      ratio [OR] = 1.26), a history of chronic obstructive pulmonary disease (OR =
      1.63), over age 85 (OR = 1.35), a surgery lasting longer than 4 hours (OR =
      1.48), or having undergone an open operation (OR = 1.53) to have increased risk
      for developing postoperative complications. Propensity score match analysis
      confirmed these results. CONCLUSIONS: Identification of preoperative factors that
      predispose patients to postoperative complications could allow for the
      institution of protocols that may decrease these events. Furthermore, expanding
      the role of laparoscopy in the treatment of older patients with colon cancer may
      decrease rates of postoperative complications.

PMID- 21169812
TI  - Effects of satiety on operant responding in rats raised in enrichment.
AB  - Rats reared in enriched environmental conditions (EC) show altered responding for
      visual novelty and psychostimulants compared with rats reared in isolated
      conditions (IC). This study investigated whether response rate was altered in EC
      and IC rats when a visual stimulus was or was not paired with sucrose delivery in
      food-deprived and free-fed rats. Male Sprague-Dawley rats were reared in EC, IC,
      or social conditions (SC) before training to lever press for liquid sucrose on a
      fixed ratio 5 schedule. Food-deprived EC rats responded significantly more than
      IC rats during acquisition and when cue lights were removed, these results were
      reversed in free-fed rats. In the absence of the cue light, IC food-deprived rats
      took more time to extinguish responding and showed greater reinstatement compared
      with EC rats. These results reveal differences between EC and IC rats in response
      to incentive value and learning abilities. During all phases, responding for SC
      rats was generally between EC and IC rats. These studies suggest that differences
      in the incentive value of the stimulus contribute to differential responding in
      EC, IC, and SC rats for sucrose paired with a cue-light reinforcer.

PMID- 21169813
TI  - Inconsistent effects of photoperiod manipulations in tests for affective-like
      changes in mice:  implications for the selection of appropriate model animals.
AB  - Deficiencies in appropriate animal models are a significant factor hindering the
      research of affective disorders. Significant data suggest that systems related to
      circadian rhythms are strongly linked to affective changes, but study with animal
      models in this context had unclear and inconsistent results. Circadian physiology
      is significantly different in diurnal and nocturnal animals and a recent project
      showed that in diurnal rodents, short photoperiods induce depression and anxiety
      like phenotypes. This study was designed to evaluate the possibility that using a
      similar methodology would also result in behavioral changes in nocturnal mice.
      Mice from two strains were maintained in either short photoperiod, neutral
      photoperiod or long photoperiod for 3 weeks and tested for depression or anxiety
      related behaviors, as done earlier with the diurnal rodents. Tests included
      activity levels, sweet solution preference, elevated plus-maze, resident-intruder
      aggression, and forced swim test. Tests were conducted either during the light
      phase or during the dark phase of the mice. In contrast to the clear phenotype in
      diurnal rodents, the effects of photoperiod manipulations in nocturnal mice were
      inconsistent. These results suggest that diurnal rodents may be advantageous
      compared with nocturnal species for studies exploring the relationship between
      circadian rhythms and affective disorders.

PMID- 21169814
TI  - Does the relation between red blood cell transfusion and mortality vary according
      to transfusion indication? A case-control study among patients with acute
      coronary syndromes.
AB  - OBJECTIVES: Red blood cell (RBC) transfusions are common among patients with
      acute coronary syndromes (ACS). We sought to determine their impact on mortality
      according to indication. METHODS: We conducted a case-control analysis of ACS
      patients admitted to a single coronary care unit. Transfused patients were
      matched to nontransfused patients for age, estimated glomerular filtration rate,
      and nadir hematocrit. Conditional logistic regression analysis was used to
      determine the independent relationship between RBC transfusion and inhospital
      mortality. Results were stratified according to the indication for transfusion.
      RESULTS: Of the 3190 patients admitted with ACS, 206 (6.4%) received at least one
      RBC transfusion. Of these, 103 patients were matched to 185 nontransfused
      patients. The most common indications for transfusion were nonspecific anemia
      (48%) and overt blood loss (42%). Transfused patients had a significantly lower
      ejection fraction and were more likely to present in Killip class IV, undergo
      pulmonary artery catheterization, and require an intra-aortic balloon pump. On
      univariate analysis, RBC transfusion was associated with a doubling of the risk
      of inhospital mortality [odds ratio: 2.0; 95% confidence interval: 1.0-3.9;
      P=0.046]. However, after adjustment for confounders, transfusion was no longer
      significantly associated with higher inhospital mortality (odds ratio: 1.8; 95%
      confidence interval: 0.6-5.1; P=0.3). On stratified analysis, RBC transfusion was
      not significantly associated with inhospital mortality among patients transfused
      for either nonspecific anemia or overt blood loss. CONCLUSIONS: Among coronary
      care unit patients with ACS, RBC transfusion does not seem to have a significant
      impact on inhospital mortality irrespective of the indication for transfusion.

PMID- 21169815
TI  - Effects of loading dose of atorvastatin before percutaneous coronary intervention
      on periprocedural myocardial injury.
AB  - OBJECTIVES: To investigate the effects of loading dose of atorvastatin on
      periprocedural myocardial injury and inflammatory reaction in patients with non
      ST segment elevation (NSTE) acute coronary syndromes (unstable angina or NSTE
      acute myocardial infarction). METHODS: A total of 81 patients with NSTE-acute
      coronary syndromes were randomly divided into the pretreatment with atorvastatin
      group [80 mg 12 h before percutaneous coronary intervention (PCI), with a further
      40 mg preprocedure dose] (n=41) or the placebo group (n=40). The main end point
      was a 30-day incidence of major adverse cardiac events (cardiac death, nonfatal
      acute myocardial infarction, or revascularization with either PCI or coronary
      artery bypass grafting). Creatine kinase-MB, cardiac troponin I, and high
      sensitivity C-reactive protein levels were measured at the baseline and at 8 and
      24 h after the procedure. RESULTS: Major adverse cardiac events occurred in 2.4%
      of patients in the atorvastatin group and 22.5% of those in the placebo group
      (P=0.0161). This difference was mostly because of reduction in the incidence of
      myocardial infarction (2.4 vs. 20.0%; P=0.0307). Markers of the two groups were
      elevated after PCI; however, the higher values of creatine kinase-MB, cardiac
      troponin I, and high-sensitivity C-reactive protein in the atorvastatin treatment
      group were significantly lower than those in the placebo group (P<0.01).
      CONCLUSION: Short-term pretreatment with a high dose of atorvastatin
      significantly reduces procedural myocardial injury in early PCI.

PMID- 21169816
TI  - The impact of intrarenal nitric oxide synthase inhibition on renal blood flow and
      function in mild and severe hyperdynamic sepsis.
AB  - OBJECTIVE: In experimental hyperdynamic sepsis, renal function deteriorates
      despite renal vasodilatation and increased renal blood flow. Because nitric oxide
      is increased in sepsis and participates in renal blood flow control, we
      investigated the effects of intrarenal Nomega-nitro-L-arginine methyl ester, a
      nonspecific nitric oxide synthase inhibitor, in mild and severe sepsis. DESIGN:
      Prospective crossover and randomized control interventional studies. SETTING:
      University-affiliated research institute. SUBJECTS: Thirty-two merino ewes.
      INTERVENTION: Examination of responses to intrarenal infusion of Nomega-nitro-L
      arginine methyl ester for 8 hrs in unilaterally nephrectomized normal sheep and
      in sheep administered Escherichia coli. MEASUREMENTS AND MAIN RESULTS: : In
      normal sheep, Nomega-nitro-L-arginine methyl ester decreased renal blood flow
      (301 +/- 30 to 228 +/- 26 mL/min) and creatinine clearance (40.0 +/- 5.8 to 31.1
      +/- 2.8 mL/min), whereas plasma creatinine increased, but fractional excretion of
      sodium was unchanged. In sheep with nonhypotensive hyperdynamic sepsis, plasma
      creatinine increased and there were decreases in creatinine clearance (34.5 +/-
      4.6 to 20.1 +/- 3.7 mL/min) and fractional excretion of sodium despite increased
      renal blood flow. Infusion of Nomega-nitro-L-arginine methyl ester normalized
      renal blood flow and increased urine output, but creatinine clearance did not
      improve and plasma creatinine and fractional excretion of sodium increased. In
      sheep with severe hypotensive sepsis, creatinine clearance decreased further
      (31.1 +/- 5.4 to 16.0 +/- 1.7 mL/min) despite increased renal blood flow.
      Infusion of Nomega-nitro-L-arginine methyl ester restored mean arterial pressure
      and reduced renal blood flow but did not improve plasma creatinine or creatinine
      clearance. CONCLUSIONS: In hyperdynamic sepsis, with or without hypotension,
      creatinine clearance decreased despite increasing renal blood flow. Intrarenal
      Nomega-nitro-L-arginine methyl ester infusion reduced renal blood flow but did
      not improve creatinine clearance. These data indicate that septic acute kidney
      injury is not the result of decreased renal blood flow nor is it improved by
      nonspecific nitric oxide synthase inhibition.

PMID- 21169818
TI  - Relationship of a common polymorphism of the glucocorticoid receptor gene to
      traumatic memories and posttraumatic stress disorder in patients after intensive
      care therapy.
AB  - OBJECTIVE: Glucocorticoids play a major role in the consolidation and retrieval
      of traumatic information. They act through the glucocorticoid receptor, for
      which, in humans, several polymorphisms have been described. In particular, the
      BclI single-nucleotide polymorphism is associated with hypersensitivity to
      glucocorticoids and with susceptibility to development of major depression.
      Furthermore, in patients with posttraumatic stress disorder carrying the BclI GG
      genotype, cortisol levels were lower and showed an inverse relationship to
      posttraumatic stress disorder symptom intensity. Here, we studied the association
      of the BclI polymorphism with plasma cortisol levels, traumatic memories,
      posttraumatic stress disorder symptoms, and health-related quality of life
      outcomes in 126 patients undergoing cardiac surgery and intensive care unit
      therapy. DESIGN: Prospective observational study. SETTING: Cardiovascular
      intensive care unit in a university hospital. PATIENTS: A total of 126 patients
      undergoing cardiac surgery and intensive care unit treatment. INTERVENTIONS: No
      interventions were performed. MEASUREMENTS AND MAIN RESULTS: Validated
      questionnaires were used to quantify end points. Measurements were taken 1 day
      before and 1 wk and 6 months after cardiac surgery. Homozygous carriers of the
      BclI G allele (n = 21) had significantly lower preoperative plasma cortisol
      levels and more long-term traumatic memories from intensive care unit therapy at
      6 months after cardiac surgery than heterozygous carriers or noncarriers (1.9 +/-
      1.4 vs. 1.0 +/- 1.2, p = .01). Anxiety was significantly more common as a long
      term traumatic memory in homozygous BclI G allele carriers than in heterozygous
      carriers or noncarriers (57% vs. 35%, p = .03). Posttraumatic stress disorder
      symptom scores were significantly higher at discharge from the intensive care
      unit in homozygous BclI G allele carriers than in heterozygous carriers or
      noncarriers. Only heterozygous carriers or BclI G allele noncarriers had a
      significant gain in health-related quality of life physical function at 6 months
      after cardiac surgery (p < .01). Baseline values were not statistically different
      between carriers of the different BclI alleles. CONCLUSION: Homozygous BclI G
      allele carriers are at risk for traumatic memories, posttraumatic stress disorder
      symptoms, and lower health-related quality of life after cardiac surgery and
      intensive care unit therapy. The BclI single-nucleotide polymorphism may help to
      identify individuals at need for tailored medical care.

PMID- 21169819
TI  - Web-based resources for critical care education.
AB  - OBJECTIVE: To identify, catalog, and critically evaluate Web-based resources for
      critical care education. DATA SOURCES: A multilevel search strategy was utilized.
      Literature searches were conducted (from 1996 to September 30, 2010) using OVID
      MEDLINE, PubMed, and the Cumulative Index to Nursing and Allied Health Literature
      with the terms "Web-based learning," "computer-assisted instruction," "e
      learning," "critical care," "tutorials," "continuing education," "virtual
      learning," and "Web-based education." The Web sites of relevant critical care
      organizations (American College of Chest Physicians, American Society of
      Anesthesiologists, American Thoracic Society, European Society of Intensive Care
      Medicine, Society of Critical Care Medicine, World Federation of Societies of
      Intensive and Critical Care Medicine, American Association of Critical Care
      Nurses, and World Federation of Critical Care Nurses) were reviewed for the
      availability of e-learning resources. Finally, Internet searches and e-mail
      queries to critical care medicine fellowship program directors and members of
      national and international acute/critical care listserves were conducted to 1)
      identify the use of and 2) review and critique Web-based resources for critical
      care education. DATA EXTRACTION AND DATA SYNTHESIS: To ensure credibility of Web
      site information, Web sites were reviewed by three independent reviewers on the
      basis of the criteria of authority, objectivity, authenticity, accuracy,
      timeliness, relevance, and efficiency in conjunction with suggested formats for
      evaluating Web sites in the medical literature. MEASUREMENTS AND MAIN RESULTS:
      Literature searches using OVID-MEDLINE, PubMed, and the Cumulative Index to
      Nursing and Allied Health Literature resulted in >250 citations. Those pertinent
      to critical care provide examples of the integration of e-learning techniques,
      the development of specific resources, reports of the use of types of e-learning,
      including interactive tutorials, case studies, and simulation, and reports of
      student or learner satisfaction, among other general reviews of the benefits of
      utilizing e-learning. Review of the Web sites of relevant critical care
      organizations revealed the existence of a number of e-learning resources,
      including online critical care courses, tutorials, podcasts, webcasts, slide
      sets, and continuing medical education resources, some requiring membership or a
      fee to access. Respondents to listserve queries (>100) and critical care medicine
      fellowship director and advanced practice nursing educator e-mail queries (>50)
      identified the use of a number of tutorials, self-directed learning modules, and
      video-enhanced programs for critical care education and practice. CONCLUSIONS: In
      all, >135 Web-based education resources exist, including video Web resources for
      critical care education in a variety of e-learning formats, such as tutorials,
      self-directed learning modules, interactive case studies, webcasts, podcasts, and
      video-enhanced programs. As identified by critical care educators and
      practitioners, e-learning is actively being integrated into critical care
      medicine and nursing training programs for continuing medical education and
      competency training purposes. Knowledge of available Web-based educational
      resources may enhance critical care practitioners' ongoing learning and clinical
      competence, although this has not been objectively measured to date.

PMID- 21169820
TI  - Polynitroxylated pegylated hemoglobin: a novel neuroprotective hemoglobin for
      acute volume-limited fluid resuscitation after combined traumatic brain injury
      and hemorrhagic hypotension in mice.
AB  - OBJECTIVE: Resuscitation of hemorrhagic hypotension after traumatic brain injury
      is challenging. A hemoglobin-based oxygen carrier may offer advantages. The novel
      therapeutic hemoglobin-based oxygen carrier, polynitroxylated pegylated
      hemoglobin (PNPH), may represent a neuroprotective hemoglobin-based oxygen
      carrier for traumatic brain injury resuscitation. HYPOTHESES: 1) PNPH is a unique
      non-neurotoxic hemoglobin-based oxygen carrier in neuronal culture and is
      neuroprotective in in vitro neuronal injury models. 2) Resuscitation with PNPH
      would require less volume to restore mean arterial blood pressure than lactated
      Ringer's or Hextend and confer neuroprotection in a mouse model of traumatic
      brain injury plus hemorrhagic hypotension. DESIGN: Prospective randomized,
      controlled experimental study. SETTING: University center. MEASUREMENTS AND MAIN
      RESULTS: In rat primary cortical neuron cultures, control bovine hemoglobin was
      neurotoxic (lactate dehydrogenase release; 3-[4,5-dimethylthiazol-2-yl-]-2,5
      diphenyltetrazolium bromide assay) at concentrations from 12.5 to 0.625 MUM,
      whereas polyethylene glycol-conjugated hemoglobin showed intermediate toxicity.
      PNPH was not neurotoxic (p<.05 vs. bovine hemoglobin and polyethylene glycol
      hemoglobin; all concentrations). PNPH conferred neuroprotection in in vitro
      neuronal injury (glutamate/glycine exposure and neuronal stretch), as assessed
      via lactate dehydrogenase and 3-[4,5-dimethylthiazol-2-yl-]-2,5
      diphenyltetrazolium bromide (all p<.05 vs. control). C57BL6 mice received
      controlled cortical impact followed by hemorrhagic hypotension (2 mL/100 g, mean
      arterial blood pressure ~35-40 mm Hg) for 90 min. Mice were resuscitated (mean
      arterial blood pressure>50 mm Hg for 30 min) with lactated Ringer's, Hextend, or
      PNPH, and then shed blood was reinfused. Mean arterial blood pressures,
      resuscitation volumes, blood gasses, glucose, and lactate were recorded. Brain
      sections at 7 days were examined via hematoxylin and eosin and Fluoro-Jade C
      (identifying dying neurons) staining in CA1 and CA3 hippocampus. Resuscitation
      with PNPH or Hextend required less volume than lactated Ringer's (both p<.05).
      PNPH but not Hextend improved mean arterial blood pressure vs. lactated Ringer's
      (p<.05). Mice resuscitated with PNPH had fewer Fluoro-Jade C positive neurons in
      CA1 vs. Hextend and lactated Ringer's, and CA3 vs. Hextend (p<.05). CONCLUSIONS:
      PNPH is a novel neuroprotective hemoglobin-based oxygen carrier in vitro and in
      vivo that may offer unique advantages for traumatic brain injury resuscitation.

PMID- 21169821
TI  - A comparison of intravascular and surface cooling techniques in comatose cardiac
      arrest survivors.
AB  - OBJECTIVES: Mild therapeutic hypothermia after out-of-hospital cardiac arrest is
      usually achieved either by surface cooling or by core cooling via the patient's
      bloodstream. We compared modern core (Coolgard) and surface (Arctic Sun) cooling
      devices with a zero hypothesis of equal cooling, complications, and neurologic
      outcomes. DESIGN: Single-center observational study. SETTING: University hospital
      medical and cardiac intensive care units. PATIENTS: One hundred sixty-seven
      consecutive patients comatose after out-of-hospital cardiac arrest of all causes
      treated with mild therapeutic hypothermia in a 5-yr period. INTERVENTIONS:
      Nonrandomized allocation to core or surface cooling depending on availability and
      physician preference. MEASUREMENTS AND MAIN RESULTS: All out-of-hospital cardiac
      arrest patients' records were reviewed for relevant data regarding medical
      history, cardiac arrest event, prehospital care, in-hospital treatment, and
      complications. Survivor neurologic function was reassessed at follow-up after 6
      to 12 months. Baseline patient and arrest episode characteristics were similar in
      the treatment groups. There was no significant difference in survival with good
      neurologic function, either to hospital discharge (surface, 34/90, 38%; core,
      34/75, 45%; p=.345) or at follow-up (surface, 34/88, 39%; core, 34/75, 45%;
      p=.387). Time from cardiac arrest to achieving mild therapeutic hypothermia was
      equal with both devices (surface, 273 min, interquartile range 158-330; core, 270
      min, interquartile range 190-360; p=.479). There were significantly more episodes
      of sustained hyperglycemia among the surface-cooled patients (surface, 64/92,
      70%; core, 36/75, 48%; p=.005) and significantly more hypomagnesaemia among core
      cooled patients (surface, 16/87, 18%; core, 27/74, 37%; p=.01). CONCLUSIONS: In
      this study, surface and core cooling of out-of-hospital cardiac arrest patients
      following the same established postresuscitation treatment protocol resulted in
      similar survival to hospital discharge and comparable neurologic function at
      follow-up.

PMID- 21169822
TI  - Use of the Airtraq laryngoscope for emergency intubation in the prehospital
      setting: a randomized control trial.
AB  - OBJECTIVES: The optical Airtraq laryngoscope (Prodol Meditec, Vizcaya, Spain) has
      been shown to have advantages when compared with direct laryngoscopy in difficult
      airway patients. Furthermore, it has been suggested that it is easy to use and
      handle even for inexperienced advanced life support providers. As such, we sought
      to assess whether the Airtraq may be a reliable alternative to conventional
      intubation when used in the prehospital setting. DESIGN, SETTING, AND PATIENTS:
      Prospective, randomized control trial in emergency patients requiring
      endotracheal intubation provided by anesthesiologists or emergency physicians
      responding with an emergency medical service helicopter or ground unit associated
      with the Department of Anesthesiology, General Hospital, Wiener Neustadt,
      Austria. MEASUREMENTS AND MAIN RESULTS: During the 18-month study period, 212
      patients were enrolled. When the Airtraq was used as first-line airway device
      (n=106) vs. direct laryngoscopy (n=106), success rate was 47% vs. 99%,
      respectively (p<.001). Reasons for failed Airtraq intubation were related to the
      fiber-optic characteristic of this device (i.e., impaired sight due to blood and
      vomitus, n=11) or to assumed handling problems (i.e., cuff damage, tube
      misplacement, or inappropriate visualization of the glottis, n=24). In 54 of 56
      patients where Airtraq intubation failed, direct laryngoscopy was successful on
      the first attempt; in the remaining two and in one additional case of failed
      direct laryngoscopy, the airway was finally secured employing the Fastrach
      laryngeal mask. There was no correlation between success rates and body mass
      index, age, indication for airway management, emergency medical service unit, or
      experience of the physicians. CONCLUSIONS: Based on these results, the use of the
      Airtraq laryngoscope as a primary airway device cannot be recommended in the
      prehospital setting without significant clinical experience obtained in the
      operation room. We conclude that the clinical learning process of the Airtraq
      laryngoscope is much longer than reported in the anesthesia literature.

PMID- 21169823
TI  - New lipoic acid derivative drug sodium zinc dihydrolipoylhistidinate prevents
      cardiac dysfunction in an isolated perfused rat heart model.
AB  - OBJECTIVE: Myocardial ischemia/reperfusion injury is a life-limiting condition.
      Reactive oxygen species are released upon reperfusion, resulting in damage to
      myocardial cells. Accordingly, antioxidant drugs have been shown to protect the
      myocardium against ischemia/reperfusion injury. The purpose of the present study
      was to determine the cardioprotective effects of the new lipoic acid-derivative
      drug sodium zinc dihydrolipoylhistidinate in a global ischemia isolated perfused
      rat heart model. DESIGN: Animals were randomly divided into five groups: 1)
      normal group, 2) control ischemia/reperfusion group, 3) high-dose sodium zinc
      dihydrolipoylhistidinate (1 ng/mL) plus ischemia/reperfusion group, 4) medium
      dose sodium zinc dihydrolipoylhistidinate (0.1 ng/mL) plus ischemia/reperfusion
      group, or 5) low-dose sodium zinc dihydrolipoylhistidinate (0.01 ng/mL) plus
      ischemia/reperfusion group. SETTING: University medical center research
      laboratory. SUBJECTS: Male Sprague-Dawley rats weighing 250-300 g. MEASUREMENTS
      AND MAIN RESULTS: Hearts underwent ischemia/reperfusion after isolation with or
      without sodium zinc dihydrolipoylhistidinate treatment. We then conducted cardiac
      histopathology and transmission electron microscopy analyses and assessed cardiac
      function. In addition, we examined the effects of sodium zinc
      dihydrolipoylhistidinate on ischemia/reperfusion-induced mitochondrial
      dysfunction. We found that cardiac dysfunction and mitochondrial damage were
      significantly reduced after reperfusion by sodium zinc dihydrolipoylhistidinate
      treatment. However, only rats treated with high-dose sodium zinc
      dihydrolipoylhistidinate showed improved cardiac function. Furthermore, treatment
      with sodium zinc dihydrolipoylhistidinate significantly improved mitochondrial
      function in vitro. CONCLUSIONS: These findings suggest that sodium zinc
      dihydrolipoylhistidinate attenuates ischemia/reperfusion-induced myocardial
      dysfunction in rats. Furthermore, sodium zinc dihydrolipoylhistidinate exerted
      cardioprotective effects via preservation of mitochondrial function. Taken
      together, our results strongly support the potential therapeutic role of sodium
      zinc dihydrolipoylhistidinate in the treatment of ischemia/reperfusion injury.

PMID- 21169824
TI  - Implementation of a real-time computerized sepsis alert in nonintensive care unit
      patients.
AB  - OBJECTIVE: Early therapy of sepsis involving fluid resuscitation and antibiotic
      administration has been shown to improve patient outcomes. A proactive tool to
      identify patients at risk for developing sepsis may decrease time to
      interventions and improve patient outcomes. The objective of this study was to
      evaluate whether the implementation of an automated sepsis screening and alert
      system facilitated early appropriate interventions. DESIGN: Prospective,
      observational, pilot study. SETTING: Six medicine wards in Barnes-Jewish
      Hospital, a 1250-bed academic medical center. PATIENTS: Patients identified by
      the sepsis screen while admitted to a medicine ward were included in the study. A
      total of 300 consecutive patients were identified comprising the nonintervention
      group (n=200) and the intervention group (n=100). INTERVENTIONS: A real-time
      sepsis alert was implemented for the intervention group, which notified the
      charge nurse on the patient's hospital ward by text page. MEASUREMENTS AND MAIN
      RESULTS: Within 12 hrs of the sepsis alert, interventions by the treating
      physicians were assessed, including new or escalated antibiotics, intravenous
      fluid administration, oxygen therapy, vasopressors, and diagnostic tests. After
      exclusion of patients without commitment to aggressive management, 181 patients
      in the nonintervention group and 89 patients in the intervention group were
      analyzed. Within 12 hrs of the sepsis alert, 70.8% of patients in the
      intervention group had received>=1 intervention vs. 55.8% in the nonintervention
      group (p=.018). Antibiotic escalation, intravenous fluid administration, oxygen
      therapy, and diagnostic tests were all increased in the intervention group. This
      was a single-center, institution- and patient-specific algorithm. CONCLUSIONS:
      The sepsis alert developed at Barnes-Jewish Hospital was shown to increase early
      therapeutic and diagnostic interventions among nonintensive care unit patients at
      risk for sepsis.

PMID- 21169827
TI  - Ventilator-associated pneumonia: role of positioning.
AB  - PURPOSE OF REVIEW: Ventilator-associated pneumonia (VAP) is a lung infection
      commonly acquired following tracheal intubation. This review assesses the role of
      the supine semirecumbent and the prone position as VAP preventive strategies and
      calls attention for further investigation on novel body positions that could
      potentially reduce risks of VAP. RECENT FINDINGS: The most recent studies on the
      semirecumbent position failed to achieve an orientation of the head of the bed
      higher than 30 degrees  and did not corroborate any benefit of the semirecumbent
      position on VAP, as reported in earlier studies. To date, there is clear evidence
      that the supine horizontal body position increases risks of pulmonary aspiration
      and VAP, particularly when patients are enterally fed. Laboratory reports are
      emphasizing the importance of an endotracheal tube-oropharynx-trachea axis below
      horizontal to avoid VAP. The prone position potentially increases drainage of
      oropharyngeal and airways secretions and recent evidence is supporting its
      beneficial effects. However, several associated adverse effects preclude its
      regular use as a VAP preventive strategy for patients other than those with acute
      respiratory distress syndrome. SUMMARY: Body position greatly affects several
      pathogenetic mechanisms of VAP. The current evidence recommends avoidance of
      supine horizontal position in order to prevent aspiration of colonized gastric
      contents. The semirecumbent position has proven benefits and should be routinely
      used but there is still limited evidence to recommend the lowest orientation of
      the bed at which the patient can be safely maintained. Results from pioneering
      laboratory investigation call attention to new possible positions, that is
      lateral Trendelenburg position, aimed to avoid pulmonary aspiration and to
      enhance mucus clearance in intubated patients.

PMID- 21169825
TI  - Lack of correlation among intracerebral cytokines, intracranial pressure, and
      brain tissue oxygenation in patients with traumatic brain injury and diffuse
      lesions.
AB  - OBJECTIVES: To determine the evolution of cytokine patterns using microdialysis
      in patients with traumatic brain injury with diffuse lesions and to study the
      relationship between cytokines and intracranial pressure, brain tissue
      oxygenation and lesion type on the computed cranial tomography scan (patients
      with and without brain swelling). DESIGN: Prospective and observational study.
      SETTING: Third-level university hospital. PATIENTS: Patients between 15 and 65
      yrs with severe traumatic brain injury and a diffuse lesion requiring
      intracranial pressure and brain tissue oxygenation monitoring were eligible.
      INTERVENTIONS: Microdialysis catheters with a high-cutoff membrane of 100 kDa
      were inserted. RESULTS: Sixteen patients were included in the analysis. There was
      a substantial interindividual variability between cytokine values. The highest
      concentrations for the interleukin-1beta, interleukin-6, and interleukin-8 were
      measured during the first 24 hrs followed by a gradual decline. The average
      concentration for interleukin-10 did not vary over time. This pattern is the most
      frequent in patients with traumatic brain injury with diffuse lesions. The
      intracranial pressure-cytokines correlation coefficients for the 16 patients
      varied substantially: interleukin-1beta-intracranial pressure (-0.76 to 0.63);
      interleukin-6-intracranial pressure (-0.83 to 0.78); interleukin-8-intracranial
      pressure (-0.86 to 0.84); and interleukin-10-intracranial pressure (-0.36 to
      0.65). The brain tissue oxygenation-cytokine correlation coefficients, like with
      intracranial pressure, also varied between patients: interleukin-1beta-brain
      tissue oxygenation (-0.49 to 0.68), interleukin-6-brain tissue oxygenation (-0.99
      to 0.84); interleukin-8-brain tissue oxygenation (-0.65 to 0.74); and interleukin
      10-brain tissue oxygenation (-0.34 to 0.52). Similarly, we found no difference in
      the cytokine values inpatient microdialysis with and without swelling in the
      computed tomographic scan. CONCLUSIONS: No clear relationship was found between
      the temporal pattern of cytokines and the behavior of the intracranial pressure,
      brain tissue oxygenation, and the presence or absence of swelling in the computed
      tomography scan. This study demonstrates the feasibility of microdialysis in
      recovering cytokines for a prolonged time, although there may be some nonresolved
      methodologic problems with this technique when we try to study the inflammation
      during traumatic brain injury that could affect the results and make
      interpretation of microdialysis data prone to difficulties.

PMID- 21169826
TI  - The acute management of intracerebral hemorrhage.
AB  - PURPOSE OF REVIEW: Spontaneous intracerebral hemorrhage (ICH) is associated with
      high morbidity and mortality, providing substantial scope for improvements in
      outcome. This review will discuss recent developments and present consensus
      evidence for the management of ICH. RECENT FINDINGS: Intracranial management
      strategies focus on preventing further bleeding and minimizing the risk of
      hematoma expansion and cerebral ischemia. Known coagulopathies should be
      corrected and oral anticoagulation reversed, but there is no evidence for the
      routine transfusion of platelets in patients taking aspirin or clopidogrel.
      Recombinant factor VIIa reduces hematoma expansion after ICH, but does not
      improve outcome and is associated with thromboembolic complications. The role and
      type of surgical interventions remain controversial. Early aggressive treatment,
      including meticulous control of blood pressure and other systemic physiological
      variables, improves outcome as does management in a specialized neurointensive
      care unit. Thromboembolic prophylaxis is routine but prophylactic antiepileptic
      drugs confer no benefit. Ongoing research seeks to define optimal blood pressure,
      glucose and temperature targets, the role and type of surgery, and potential
      neuroprotective strategies. SUMMARY: Well organized, multimodal therapy
      optimizing intracranial and systemic physiological variables improves outcome
      after ICH. Recent guidelines provide a useful consensus evidence-based framework
      for the management of acute ICH.

PMID- 21169830
TI  - Panton-Valentine leucocidin and severe Staphylococcus aureus infections of the
      skin: sole culprit or does it have accomplices?

PMID- 21169828
TI  - Positron emission tomography: a tool for better understanding of ventilator
      induced and acute lung injury.
AB  - PURPOSE OF REVIEW: PET has recently gained traction among several groups of
      investigators as an imaging tool to study lung pathophysiology in vivo
      noninvasively on a regional basis. This review aims to present the major findings
      of PET studies on acute lung injury (ALI) and ventilator-induced lung injury
      (VILI) with a perspective relevant to the physiologist-intensivist. RECENT
      FINDINGS: Using various tracers, PET has been used to investigate the
      relationship between the distributions of pulmonary perfusion, ventilation and
      aeration, and the effect of positive end-expiratory pressure, recruitment
      maneuvers, prone positioning, and endotoxin on these distributions in ALI. More
      recently, PET with 2-[18F]fluoro-2-deoxy-D-glucose has been used to measure
      regional neutrophil metabolic activation in ALI and VILI. Because gas exchange
      impairment and inflammation are two hallmarks of ALI and VILI, these studies have
      provided significant insights into the pathophysiology of these conditions.
      SUMMARY: PET is a versatile imaging tool for physiologic investigation. By
      imaging the regional effects of interventions commonly performed in critically
      ill patients with ALI, PET has improved our understanding of the mechanism by
      which such interventions can exert their positive or negative effects as well as
      of the pathophysiology of ALI and VILI.

PMID- 21169829
TI  - Sedation, delirium and mechanical ventilation: the 'ABCDE' approach.
AB  - PURPOSE OF REVIEW: Delirium and ICU-acquired weakness are frequent in critically
      ill mechanically ventilated patients. The number of mechanically ventilated
      patients is increasing, placing more patients at risk for these adverse outcomes.
      Sedation is given to ensure comfort and to minimize distress, but is linked to
      delirium and immobility. We review recent findings on the management of
      mechanically ventilated patients focusing on strategies that may improve
      neurologic and functional outcomes in critically ill patients. RECENT FINDINGS:
      We present the evidence-based 'ABCDE' bundle, an integrated and interdisciplinary
      approach to the management of mechanically ventilated patients. Spontaneous
      awakening and breathing trials have been combined into 'awake and breathing
      coordination', shortening the duration of mechanical ventilation, ICU and
      hospital length of stay and improving survival. The choice of alpha-2 agonists
      reduces ICU delirium and duration of mechanical ventilation. Delirium monitoring
      improves recognition of this disorder, but data on pharmacologic treatment are
      mixed. Early mobility and exercise may reduce physical dysfunction and delirium
      rates. SUMMARY: Outcomes of critically ill patients can be improved by applying
      evidence-based therapies for the 'liberation' from mechanical ventilation and
      sedation, and the 'animation' through early mobilization. Clinicians should be
      aware of organizational approaches such as the 'ABCDE' bundle to improve the
      management of mechanically ventilated patients.

PMID- 21169831
TI  - Tinea imbricata in the Americas.
AB  - PURPOSE OF REVIEW: The aim is to provide an overview on tinea imbricata, or
      Tokelau, a superficial mycosis caused by Trichophyton concentricum, a strictly
      anthropophilic dermatophyte with a well-defined geographic distribution and
      predisposing factors that include genetic, racial and immunologic susceptibility
      patterns and a specific environment. RECENT FINDINGS: This review covers the most
      interesting aspects of the infrequent disease tinea imbricata, including the
      historical background, the epidemiologic aspects, highlighting the genetic and
      racial patterns of susceptibility to the acquisition of the disease, and the
      immunologic aspects that help to explain its clinical behavior. We also present a
      clinical description of the disease, the differential diagnosis and how currently
      some other emerging diseases such as syphilis in immunocompromised patients can
      mimic tinea imbricata. The therapeutic options are still griseofulvin and
      nowadays terbinafine, but the access to the treatments in the endemic zones and
      the changes in habits of the affected population make control and prevention of
      the disease difficult. SUMMARY: Tinea imbricata, or Tokelau, remains an
      infrequent superficial mycosis restricted to endemic zones in the South Pacific
      islands (Polynesia and Melanesia), South Asia and some specific areas of South
      America. Migration phenomena and global changes in the climate may modify the
      incidence and characteristics of the disease.

PMID- 21169832
TI  - Skin infections in HIV-infected individuals in the era of HAART.
AB  - PURPOSE OF REVIEW: Clinicians should be aware of the shift in the cutaneous
      infectious disease burden in human immunodeficiency virus-infected individuals as
      a reflection of immune restoration in the era of highly active antiretroviral
      therapy (HAART). RECENT FINDINGS: As in the general population but to greater
      extent, methicillin-resistant Staphylococcus aureus (MRSA) soft-tissue infection
      is a rising problem among those with human immunodeficiency virus (HIV). Human
      papilloma virus (HPV) is exceedingly prevalent and persistent despite HAART, and
      HPV-associated malignancy is increasing as those with HIV live longer. Herpes,
      syphilis, and Kaposi's sarcoma continue to plague individuals with HIV. Immune
      reconstitution inflammatory syndrome (IRIS) is common and often presents with
      infectious cutaneous manifestations. SUMMARY: This review implicates the
      importance of the acknowledgment of MRSA infections risk factors, screening for
      HPV-related neoplasia, continuance of trials to establish the efficacy of herpes
      vaccines, and awareness of prevalent cutaneous infections presenting with IRIS in
      those with HIV.

PMID- 21169833
TI  - High-dose chemotherapy and multiple sclerosis.
AB  - PURPOSE OF REVIEW: Immunomodulatory medications for multiple sclerosis provide
      only modest control of this potentially debilitating auto-immune disease of the
      central nervous system. The immunosuppression provided by high-dose chemotherapy
      has been studied to address treatment-refractory disease. In this review, we
      discuss the recent significant work in this field and its associated
      controversies. RECENT FINDINGS: Conclusive evidence for the efficacy of high-dose
      chemotherapy with stem cell rescue is lacking given the lack of uniform patient
      populations and varying treatment protocols. Moreover, the significant toxicity
      associated with this procedure has dampened enthusiasm for its widespread use.
      High-dose chemotherapy without stem cell rescue has been trialed as a less toxic
      approach that eliminates the possibility of re-infusing autoreactive lymphocytes
      found in the stem cell product. SUMMARY: Before high-dose chemotherapy with or
      without stem cell rescue can be adopted for clinical practice, both approaches
      require testing in randomized clinical trials. Both procedures have the
      possibility of decreasing disease activity but high-dose chemotherapy without
      stem cell rescue having a more favorable safety profile, may prove a more
      significant advance in the field of high-dose therapy for multiple sclerosis.

PMID- 21169834
TI  - Stem cell transplantation for diffuse large B-cell lymphoma patients in the
      rituximab era.
AB  - PURPOSE OF REVIEW: Addition of rituximab to conventional chemotherapies was shown
      to improve outcome in phase 3 trials of patients with diffuse large B-cell
      lymphoma (DLBCL). As the challenge in the rituximab era is to increase treatment
      efficacy, the present review attempts to assess the results of high-dose therapy
      and autologous stem cell transplantation (ASCT) as front-line treatment for poor
      prognosis DLBCL patients. RECENT FINDINGS: French and Italian groups demonstrated
      in several phase 2 series that high-dose front-line treatment with rituximab plus
      ASCT gave better results than without rituximab. In relapse, the CORAL study, a
      worldwide collaborative effort, showed that assessment of the latest results for
      ASCT should also take account of other prognostic factors, including advanced
      stage, chemo/rituximab refractory disease and a short interval between remission
      and relapse. This underscores the need for innovative therapeutic strategies such
      as radiolabelled conditioning regimens and maintenance after ASCT. Allogeneic
      transplantation, which generates a graft-versus-lymphoma effect that reduces the
      likelihood of relapse, may also be beneficial for high-risk patients. SUMMARY: In
      this setting, new approaches based on improved understanding of the biology of
      the disease will play a key role.

PMID- 21169835
TI  - How new advances in genetic analysis are influencing the understanding and
      treatment of childhood acute leukemia.
AB  - PURPOSE OF REVIEW: This review describes the recent advances in genomic profiling
      that have provided critical new insights into the biology of acute leukemia in
      children. RECENT FINDINGS: Acute leukemia genomes commonly harbor submicroscopic
      gains and deletions of DNA which target key cellular pathways that influence
      leukemogenesis and the likelihood of treatment failure, particularly in acute
      lymphoblastic leukemia (ALL). Notably, genetic alterations targeting
      transcriptional regulators of lymphoid development are a hallmark of B-progenitor
      ALL, and alteration of specific genes in this pathway, such as IKZF1 (encoding
      IKAROS), are associated with high-risk ALL. Integrated genomic profiling has
      identified potential therapeutic targets in ALL, including aberrant cytokine
      receptor signaling mediated by rearrangements and mutation of CRLF2 and JAK2.
      Genome-wide association studies are also providing important insights into the
      role of inherited genetic variation and susceptibility to ALL. In contrast,
      genomic profiling of acute myeloid leukemia (AML) has thus far yielded fewer
      insights, but ongoing resequencing of leukemia genomes is uncovering novel
      mutations in both ALL and AML. SUMMARY: Genomic profiling has identified
      important new genetic lesions that contribute to leukemogenesis. These findings
      will have important implications for the development of new diagnostic tests and
      treatment approaches in high-risk leukemia. Future studies will be increasingly
      reliant on comprehensive genomic sequencing to reveal the spectrum of genetic
      alterations in this disease, with the ultimate aim of improving the treatment
      outcome for leukemia patients.

PMID- 21169836
TI  - The new bronchopulmonary dysplasia.
AB  - PURPOSE OF REVIEW: Bronchopulmonary dysplasia (BPD) remains the most common
      severe complication of preterm birth. A number of recent animal models and
      clinical studies provide new information about pathophysiology and treatment.
      RECENT FINDINGS: The epidemiology of BPD continues to demonstrate that birth
      weight and gestational age are most predictive of BPD. Correlations of BPD with
      chorioamnionitis are clouded by the complexity of the fetal exposures to
      inflammation. Excessive oxygen use in preterm infants can increase the risk of
      BPD but low saturation targets may increase death. Numerous recent trials
      demonstrate that many preterm infants can be initially stabilized after delivery
      with continuous positive airway response (CPAP) and then be selectively treated
      with surfactant for respiratory distress syndrome. The growth of the lungs of the
      infant with BPD through childhood remains poorly characterized. SUMMARY: Recent
      experiences in neonatology suggest that combining less invasive care strategies
      that avoid excessive oxygen and ventilation, decrease postnatal infections, and
      optimize nutrition may decrease the incidence and severity of BPD.

PMID- 21169837
TI  - Surgical epiphysiodesis indications and techniques: update.
AB  - PURPOSE OF REVIEW: To present a summary of epiphysiodesis indications and to
      report most recent advances in the field, along with their clinical relevance.
      RECENT FINDINGS: Percutaneous epiphysiodesis using transphyseal screws (PETS) and
      guided growth using eight plates represent the most recent techniques used for
      hemiepiphysiodesis. SUMMARY: PETS and guided growth have yielded very good
      results and low rates of complications and are the current standard for the
      management of angular deformities of the lower extremities in children. Permanent
      percutaneous epiphysiodesis remains the preferred method for the treatment of
      limb length discrepancies.

PMID- 21169838
TI  - Evaluation and treatment of symptomatic pes planus.
AB  - PURPOSE OF REVIEW: To provide the pediatrician with a comprehensive synopsis of
      pediatric pes planus, also known as flatfoot. The term pes planus is a physical
      finding that generates some confusion in the medical community because it
      describes a spectrum of conditions that are diagnosed and managed differently.
      RECENT FINDINGS: Some of the recent data incorporated in this review come from
      pediatric, orthopaedic, and podiatric literature. These sources describe the
      clinical features and the latest treatment options for pes planus. SUMMARY: This
      article will provide some guidance to evaluate and treat the many causes of
      pediatric pes planus. Nonsurgical and operative management will be discussed.

PMID- 21169839
TI  - Insights into chronic obstructive pulmonary disease patient attitudes on
      ventilatory support.
AB  - PURPOSE OF REVIEW: A large proportion of chronic obstructive pulmonary disease
      (COPD) patients do not actually discuss ventilation and other end-of-life issues
      in the stable state. Such discussions often occur during the exacerbation itself.
      There is a paucity of data regarding attitudes of COPD patients toward end-of
      life attitudes in general and specifically concerning the area of ventilatory
      support. RECENT FINDINGS: The majority of COPD patients feel end-of-life
      discussions are warranted in the stable state. Some studies have shown that
      increasing age and the presence of depression preclude patients from choosing
      life-sustaining treatment, whereas physicians were often inaccurate in judging
      patient preference for cardiopulmonary resuscitation and ventilation as they
      frequently underestimated patient quality of life. Patient information sheets and
      other tools may have a role as decision aids in end-of-life discussions. SUMMARY:
      Physicians should consider the discussion of end-of-life issues preferably when
      patients are stable. Decision aids may prove to be a valuable adjunct in framing
      treatments such as mechanical ventilation.

PMID- 21169840
TI  - Obstructive sleep apnea in chronic obstructive pulmonary disease patients.
AB  - PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) and obstructive
      sleep apnea (OSA) represent two of the most prevalent chronic respiratory
      disorders and cardiovascular diseases are major co-morbidities in both. Co
      existence of both disorders (overlap syndrome) occurs in 1% of adults and overlap
      patients have worse nocturnal hypoxemia and hypercapnia than COPD and OSA
      patients alone. The present review discusses recent data concerning the
      pathophysiological and clinical significance of the overlap syndrome. RECENT
      FINDINGS: The severity of obstructive ventilatory impairment and hyperinflation,
      especially the inspiratory capacity to total lung capacity (TLC) ratio,
      correlates with the severity of sleep-related breathing disturbances. Early
      treatment with continuous positive airway pressure (CPAP) improves survival,
      reduces hospitalization and pulmonary hypertension, and also reduces hypoxemia.
      Evidence of systemic inflammation and oxidative stress in COPD and sleep apnea
      provides insight into potential interactions between both disorders that may
      predispose to cardiovascular disease. Long-term outcome studies of overlap
      patients currently underway should provide further evidence of the clinical
      significance of the overlap syndrome. SUMMARY: Studies of overlap syndrome
      patients at a clinical, physiological and molecular level should provide insight
      into disease mechanisms and consequences of COPD and sleep apnea, in addition to
      identifying potential relationships with cardiovascular disease.

PMID- 21169841
TI  - Gout and hyperuricemia in young people.
AB  - PURPOSE OF REVIEW: Although gout and hyperuricemia have received considerable
      attention recently, there is limited information on the two conditions in young
      people. The molecular mechanisms of hyperuricemia have been investigated
      extensively in recent years, with this knowledge providing new insights and a
      better understanding of the precocious onset of gout and hyperuricemia. RECENT
      FINDINGS: Serum uric acid levels are higher in the younger generation compared
      with the older generation. A proportion of gout and hyperuricemia in childhood is
      due to inborn errors in purine metabolism. Extensive investigation has
      demonstrated genetic polymorphisms in the urate transporter associated with
      hyperuricemia and gout. Whether or not polymorphisms affect the onset of gout and
      hyperuricemia in young people is unclear. Uric acid levels in childhood have also
      been shown to correlate with the development of the metabolic syndrome. SUMMARY:
      Elevations in serum uric acid levels in childhood are often associated with other
      diseases and allied conditions. Hyperuricemia in young individuals is often a
      marker of the metabolic syndrome. Gout is not common in childhood compared with
      adulthood, and careful consideration of inborn errors of metabolism should be
      considered in these cases.

PMID- 21169842
TI  - Crystals, inflammation, and osteoarthritis.
AB  - PURPOSE OF REVIEW: Calcium pyrophosphate dihydrate (CPPD) and basic calcium
      phosphate (BCP) crystals are common components of osteoarthritic joint fluids and
      tissues. Why these crystals form and how they contribute to joint damage in
      osteoarthritis remain unclear. With renewed interest in inflammation as a key
      component of osteoarthritis the role of calcium-containing crystals in this
      common disease warrants re-examination. RECENT FINDINGS: There is ample evidence
      supporting a pathogenic role for inflammation in osteoarthritis, and the innate
      immune system likely participates in this inflammatory process. Recent work
      reinforces the almost universal existence of calcium-containing crystals in
      tissues from patients with end-stage osteoarthritis. Calcium-containing crystals
      may contribute to inflammation in osteoarthritis tissues through their direct
      interactions with components of the innate immune system, as well as by inducing
      or amplifying other inflammatory signals. SUMMARY: There is increasing evidence
      that calcium-containing crystals contribute to osteoarthritis and their
      inflammatory properties may mediate detrimental effects through innate immunity
      signals. Calcium-containing crystals may thus represent important therapeutic
      targets in osteoarthritis.

PMID- 21169843
TI  - A timely arrival for genomic medicine.

PMID- 21169844
TI  - Multifocal nodular periostitis associated with prolonged voriconazole therapy in
      a lung transplant recipient.
AB  - We report a case of painful, nodular periostitis in a lung transplant recipient
      on long-term voriconazole therapy. Symptoms, signs, and laboratory abnormalities
      resolved quickly after drug withdrawal. The presentation more closely resembles
      periostitis deformans than hypertrophic osteoarthropathy, suggesting that the
      fluoride moiety of voriconazole may be pathogenic for this condition. Clinicians
      should be aware of this association.

PMID- 21169845
TI  - Tophaceous gout in a knee with total joint replacement.

PMID- 21169846
TI  - Hypoglycemia induced by hydroxychloroquine in a patient treated for rheumatoid
      arthritis.

PMID- 21169847
TI  - Resolution of recurrent fusarium arthritis after prolonged antifungal therapy.

PMID- 21169848
TI  - Spontaneous pneumomediastinum in a patient with anti-centromere antibody-positive
      limited scleroderma.

PMID- 21169849
TI  - Fibrodysplasia ossificans progressiva in South Africa: difficulties in management
      in a developing country.
AB  - Fibrodysplasia ossificans progressiva is a rare genetic disorder in which
      progressive ossification of connective tissue leads to severe disability. The
      condition is an autosomal dominant trait, and most of the affected persons
      represent new mutations for the determinant gene, ACVR1, chromosomal locus 2q23
      24. Although fibrodysplasia ossificans progressiva has a worldwide distribution,
      there are only a few reports of affected persons of indigenous African stock. We
      studied and documented 3 affected individuals in the African (Xhosa) community
      from South Africa. In addition to describing the manifestations and natural
      history of the disorder in Africa, we discuss the challenge of management of this
      condition in the South African context.

PMID- 21169850
TI  - Squamous cell carcinomas arising in discoid lupus erythematosus scars: unusual
      occurrence in an African-American and in a sun-protected area.
AB  - Squamous cell carcinoma is a known and rare complication of long-standing discoid
      lupus erythematosus. Most cases have been reported in sun-exposed skin of whites.
      We report 2 unusual cases of squamous cell carcinoma arising in discoid lupus
      erythematosus scars: one in a sun-protected area of a white patient and a second
      in an African-American patient.

PMID- 21169851
TI  - Is fluorine 18 fluorodeoxyglucose positron emission tomography scanning a
      suitable diagnostic test for histologically active large-vessel vasculitis?
AB  - Recent publications have highlighted the use of fluorine 18 fluorodeoxyglucose (F
      FDG) positron emission tomography (PET) as a moderately sensitive, noninvasive
      diagnostic test for medium- and large-vessel vasculitis. We report the atypical
      case of a patient with biopsy-proven granulomatous vasculitis of the aorta in
      addition to a non-small cell lung cancer, whose whole-body F-FDG PET/computed
      tomography scan demonstrated metabolic activity within the lung malignancy but
      was metabolically inactive in the aorta. We submit that F-FDG PET may not be an
      accurate diagnostic test for histologically active large-vessel vasculitis and
      should be used with caution.

PMID- 21169852
TI  - Colchicine-induced rhabdomyolysis in a heart/lung transplant patient with
      concurrent use of cyclosporin, pravastatin, and azithromycin.
AB  - We report a case of colchicine-induced rhabdomyolysis in a heart/lung
      transplanted man treated with cyclosporin. A treatment was to resolve an acute
      gouty arthritis and was started with 3 mg of colchicine the first day, then 2 mg
      the second and the third day, and finally 1 mg/d during 6 days. Eight days later,
      the patient developed multiple organ failure and rhabdomyolysis. The
      concentration of colchicine analyzed was greater than the standard 153 hours
      after his last intake. Pharmacokinetic interactions are responsible of this
      toxicity. Cyclosporin, pravastatin, and azithromycin are known to inhibit P
      glycoprotein, which will enhance the intracellular colchicine level by acting in
      its bioavailability and moderating hepatic and renal excretion. Moreover, long
      term treatment by cyclosporin generates chronic renal failure that will, in the
      same time, decrease colchicine elimination. Even short-term administration of
      therapeutic colchicine dose may cause colchicine-related toxicity, especially in
      the setting of a renal failure and/or polymedicinal treatment.

PMID- 21169817
TI  - Candida bloodstream infections in intensive care units: analysis of the extended
      prevalence of infection in intensive care unit study.
AB  - OBJECTIVES: To provide a global, up-to-date picture of the prevalence, treatment,
      and outcomes of Candida bloodstream infections in intensive care unit patients
      and compare Candida with bacterial bloodstream infection. DESIGN: A retrospective
      analysis of the Extended Prevalence of Infection in the ICU Study (EPIC II).
      Demographic, physiological, infection-related and therapeutic data were
      collected. Patients were grouped as having Candida, Gram-positive, Gram-negative,
      and combined Candida/bacterial bloodstream infection. Outcome data were assessed
      at intensive care unit and hospital discharge. SETTING: EPIC II included 1265
      intensive care units in 76 countries. PATIENTS: Patients in participating
      intensive care units on study day. INTERVENTIONS: None. MEASUREMENT AND MAIN
      RESULTS: Of the 14,414 patients in EPIC II, 99 patients had Candida bloodstream
      infections for a prevalence of 6.9 per 1000 patients. Sixty-one patients had
      candidemia alone and 38 patients had combined bloodstream infections. Candida
      albicans (n = 70) was the predominant species. Primary therapy included
      monotherapy with fluconazole (n = 39), caspofungin (n = 16), and a polyene-based
      product (n = 12). Combination therapy was infrequently used (n = 10). Compared
      with patients with Gram-positive (n = 420) and Gram-negative (n = 264)
      bloodstream infections, patients with candidemia were more likely to have solid
      tumors (p < .05) and appeared to have been in an intensive care unit longer (14
      days [range, 5-25 days], 8 days [range, 3-20 days], and 10 days [range, 2-23
      days], respectively), but this difference was not statistically significant.
      Severity of illness and organ dysfunction scores were similar between groups.
      Patients with Candida bloodstream infections, compared with patients with Gram
      positive and Gram-negative bloodstream infections, had the greatest crude
      intensive care unit mortality rates (42.6%, 25.3%, and 29.1%, respectively) and
      longer intensive care unit lengths of stay (median [interquartile range]) (33
      days [18-44], 20 days [9-43], and 21 days [8-46], respectively); however, these
      differences were not statistically significant. CONCLUSION: Candidemia remains a
      significant problem in intensive care units patients. In the EPIC II population,
      Candida albicans was the most common organism and fluconazole remained the
      predominant antifungal agent used. Candida bloodstream infections are associated
      with high intensive care unit and hospital mortality rates and resource use.

PMID- 21169853
TI  - Rapid and sustained remission of systemic juvenile idiopathic arthritis
      associated macrophage activation syndrome through treatment with anakinra and
      corticosteroids.
AB  - We describe 2 patients with systemic juvenile idiopathic arthritis and macrophage
      activation syndrome. Treatment with recombinant interleukin 1 receptor antagonist
      (anakinra) and a corticosteroid rapidly induced remission, which could be
      maintained with anakinra monotherapy at a stable dose of 2 mg/kg per day. Pain at
      the injection site during the initial injections was the only adverse effect
      attributable to anakinra. Untoward effects of corticosteroid treatment were mild
      because prolonged therapy with high-dose corticosteroids could be avoided. These
      results suggest that early institution of interleukin 1 blockade merits further
      investigation for the treatment of macrophage activation syndrome and, perhaps,
      related conditions such as hemophagocytic lymphohistiocytosis.

PMID- 21169854
TI  - Prevalence of subclinical enthesopathy in patients with spondyloarthropathy: an
      ultrasound study.
AB  - BACKGROUND: Ultrasound has demonstrated to be a highly sensitive tool in the
      evaluation of entheses in spondyloarthropathy (SpA) patients and improves the
      ability of clinical examination to detect enthesopathy. OBJECTIVES: The
      objectives of the study were to determine the prevalence of subclinical
      enthesopathy in SpA patients and to evaluate the reliability of ultrasound in the
      detection of abnormal findings indicative of enthesopathy. METHODS: Six hundred
      lower-limb entheses were assessed in 60 SpA patients without known history of
      entheseal involvement. Sixty rheumatoid arthritis patients and 30 control
      subjects were included as control groups. Clinical examination and ultrasound
      were consecutively performed at each of the entheses to detect signs indicative
      of enthesopathy. Images from 20 SpA patients were stored and afterward evaluated
      to determine the reliability of abnormal ultrasound findings. RESULTS: Ultrasound
      detected a high prevalence of enthesopathy in SpA patients with respect to both
      rheumatoid arthritis patients and control subjects (P < 0.001 for both
      comparisons). In SpA patients, clinical examination detected enthesopathy in 56
      (9.3%) of 600 entheses. In the remainder 544 clinically asymptomatic entheses
      (90.7%) (not painful and not swollen), ultrasound detected in 331 (60.8%) at
      least 1 ultrasound sign of enthesopathy. The intrareader and interreader
      agreement for all ultrasound abnormal findings was good to excellent. CONCLUSION:
      The present study demonstrates a higher sensitivity of ultrasound with respect to
      physical examination in the detection of signs indicative of enthesopathy in SpA
      patients with an adequate interreader and intrareader reliability. Further study
      is needed about the prognostic value of the ultrasound findings for predicting
      clinical onset of entheseal involvement.

PMID- 21169855
TI  - Disease-modifying antirheumatic drugs increase serum adiponectin levels in
      patients with rheumatoid arthritis.
AB  - BACKGROUND: Adiponectin is an adipocyte-derived adipokine with immunosuppressive
      and anti-inflammatory properties. It also decreases expression of adhesion
      molecules. In terms of its relationship with acute-phase reactants, there are
      conflicting results in patients with rheumatoid arthritis (RA). OBJECTIVES: The
      objectives of this study were to evaluate the levels of adiponectin in RA
      patients before and after the treatment with disease-modifying antirheumatic
      drugs (DMARDs) and to evaluate whether there is a correlation between adiponectin
      levels and disease activity and acute-phase-response reactants (APRRs). METHODS:
      Serum adiponectin levels, APRRs, total and high-density lipoprotein cholesterol
      (HDL-C), body mass index, and body fat mass were measured in 27 patients with RA
      before and after the treatment with DMARDs plus prednisolone. An inclusion
      criterion for RA patients was to be DMARD naive for at least 6 months or to have
      been newly diagnosed with RA. Twenty patients with osteoarthritis were included
      in this study as a disease control. RESULTS: No significant difference was found
      between RA and osteoarthritis group in terms of baseline adiponectin level. Mean
      adiponectin level and mean HDL-C level increased significantly compared with mean
      baseline level after the treatment with DMARDs plus prednisolone (10 [SD, 4.9]
      vs. 13.9 [SD, 8.7] MUg/mL; P < 0.001; 56.8 [SD, 19] vs. 65 [SD, 18] mg/dL, P <
      0.004, respectively). APRRs and the 28-joint-count disease activity score
      decreased significantly at the end of the 3 months of therapy. The adiponectin
      levels tended to be negatively correlated with acute-phase reactants and disease
      activity, although no changes were significant. There was a positive correlation
      between HDL-C and adiponectin levels at 3 month (r = 0.53, P < 0.001). No
      correlation was found between erythrocyte sedimentation rate and adiponectin
      levels both at baseline and at 3 months. CONCLUSION: Adiponectin levels can be
      modified by effective treatment of rheumatoid arthritis. This suggests that
      active inflammation may decrease serum adiponectin levels. In consideration of
      the antiatherogenic and anti-inflammatory features of adiponectin, increased
      adiponectin levels in patients with RA may result in a more favorable
      cardiovascular profile.

PMID- 21169856
TI  - Renal function in gout: long-term treatment effects of febuxostat.
AB  - BACKGROUND: The association between hyperuricemia, gout, and impaired renal
      function has long been recognized. Recent data provide evidence for the causal
      relationship between elevated serum urate (sUA) and renal changes, leading to
      declines in glomerular filtration rates. In healthy adults, glomerular filtration
      rate wanes with age. Urate-lowering therapy (ULT) with allopurinol has been shown
      to stabilize or reverse this. OBJECTIVE: Here we examine the long-term effects of
      ULT with febuxostat on estimated glomerular filtration rate (eGFR). METHODS: This
      is a post hoc analysis of the Febuxostat Open-label Clinical trial of Urate
      lowering efficacy and Safety study, during which 116 hyperuricemic gout subjects
      received daily doses of febuxostat (40, 80, or 120 mg) for up to 5 years. sUA
      concentrations and eGFR were assessed regularly. Results were stratified by mean
      change in sUA from baseline. Mathematical modeling was used to predict the effect
      of sUA reduction on eGFR. RESULTS: Maintenance or improvement in eGFR was
      inversely correlated with the quantitative reduction in sUA from baseline. For
      every 1 mg/dL decrease in sUA, the model projected an expected improvement in
      eGFR of 1 mL/min from the untreated value. CONCLUSION: Individuals with the
      greatest reductions in sUA may experience reduced rates of renal deterioration or
      even stabilization of renal function. Further studies examining the impact of
      long-term ULT on renal function in hyperuricemic gout patients are needed to both
      confirm our results and verify if improvements in renal function are feasible in
      such patients.

PMID- 21169857
TI  - The experience and impact of living with gout: a study of men with chronic gout
      using a qualitative grounded theory approach.
AB  - BACKGROUND: Gout is commonly undertreated and can lead to significant disability.
      Few data are available about the lived experience of gout or the barriers to
      effective urate-lowering therapy in men with gout. AIMS: This study aims to
      understand the experience of men living with chronic gout using a qualitative
      grounded theory approach. METHODS: Eleven English-speaking men with chronic gout
      participated in an in-depth semistructured interview about their experiences of
      living with gout. Interviews were recorded and transcribed. Consensus groups were
      used to analyze and validate the themes arising from the transcripts. RESULTS:
      Three major themes related to the experience of gout emerged from the interviews:
      the impact of disease (pain, dependency on family members during flares,
      isolation, work disability), the progressiveness of untreated gout (increasing
      number of affected joints and frequency of flares, increase in food type
      triggers, escalating treatment required to control flares due to reducing
      efficacy of anti-inflammatory medication), and the lack of knowledge of gout (a
      community wide lack of understanding of the causes or prevention of gout,
      stoicism/tolerance to symptoms and disability, personal and social stigma related
      to gout). DISCUSSION: Chronic gout has an important impact on both the patient
      and his family. This work provides previously hidden perspectives of the
      experience of gout, which may be generalized to other men with gout, suggesting
      that shame, embarrassment, and stigma lead to trivialization of the impact of
      disease despite its severity. These experiences may lead to undertreatment of
      gout because of lack of disclosure of symptom severity and lack of expectation of
      treatment effectiveness, which in turn could contribute to the development of
      progressive gout.

PMID- 21169858
TI  - High rates of school readiness difficulties at 5 years of age in very preterm
      infants compared with term controls.
AB  - OBJECTIVE: School readiness is best understood as a framework for assessing
      profiles of strengths and vulnerabilities of the preschool-age child. Very
      preterm (VPT) children are at high risk of difficulties in school, and
      understanding their school readiness skills has the potential to aid successful
      transition into school. The aim of this study was to determine the school
      readiness skills of a cohort of VPT children, compared with term controls.
      METHODS: VPT children (gestational age <30 wk or birth weights <1250 g) and term
      controls were enrolled from a tertiary maternity hospital, Melbourne, Australia
      into a prospective cohort study. At age 5 years, school readiness skills were
      evaluated using a combination of parent questionnaires and direct assessments.
      The 5 domains of school readiness assessed were health and physical development,
      social-emotional skills, approaches to learning, communication skills, and
      cognitive skills. RESULTS: VPT children had standard scores ~1/2 to 1 SD below
      those of the term controls in all domains of school readiness, and these
      differences were not greatly affected by adjustment for social risk differences.
      Overall, 44% of the VPT group had vulnerabilities in more than 1 domain of school
      readiness, compared with only 16% of the term controls. CONCLUSIONS: VPT children
      are more likely than term controls to have significant vulnerabilities in
      multiple domains of school readiness, and these differences are mostly
      independent of social risk.

PMID- 21169859
TI  - Attributions and expectations for the behavior of persons with brain injury: the
      effect of visibility of injury.
AB  - OBJECTIVE: To determine whether visible markers of brain injury shape people's
      causal attributions for the behaviors of the person with the injury and their
      expectations that those behaviors will persist for 5 years. DESIGN: Experimental
      scenarios described an adolescent boy with a brain injury (pictured either with
      or without a head scar) who showed 4 behavior changes relating to sleep, anger,
      self-confidence, and motivation. SETTING: Victoria University of Wellington.
      PARTICIPANTS: University student volunteers (N = 249). MEASURES: For each
      behavior, ratings of attributions to either the brain injury or to adolescence
      and estimates that the behaviors would persist for 5 years. RESULTS: Attributions
      to brain injury correlated with expectations that the behaviors would persist.
      Participants attributed the behaviors more to the brain injury than to
      adolescence in the scar condition but not in the no-scar condition. CONCLUSIONS:
      Visible markers of brain injury such as scars are spurious markers of severity
      that shape attributions for actions of persons with the injury and expectations
      that problematic behaviors will persist. The results inform strategies for
      correcting misunderstandings about brain injury and enhancing rehabilitation.

PMID- 21169860
TI  - Rehabilitation of executive functioning with training in attention regulation
      applied to individually defined goals: a pilot study bridging theory, assessment,
      and treatment.
AB  - OBJECTIVE: To assess feasibility and effects of training in goal-oriented
      attentional self-regulation for patients with brain injury and chronic executive
      dysfunction. PARTICIPANTS: Sixteen individuals with chronic brain injury and mild
      to moderate executive dysfunction. DESIGN: Participants were divided into 2
      groups: one group completed goal-oriented attentional self-regulation training
      during the first 5 weeks, followed by a brief (2-hour) educational instruction
      session as a control midway through the second 5 weeks; the other group
      participated in reverse order. MEASURES: Neuropsychological and functional
      performance assessed at baseline and at weeks 5 and 10. RESULTS: Participants
      found training in goal-oriented attentional self-regulation engaging,
      incorporated some trained strategies into daily life, and reported subjective
      improvements in personal functioning. At week 5, participants who completed goals
      training significantly improved on tests of attention and executive function and
      had fewer functional task failures, while performance did not change after
      educational instruction. At week 10, participants who crossed over from
      educational instruction to goals training also significantly improved on
      attention and executive function tests. Participants who crossed from goals
      training to educational instruction maintained their week 5 gains. CONCLUSIONS:
      Training in goal-oriented attentional self-regulation is theoretically driven and
      feasible in a research setting. Pilot results suggest improvements in cognitive
      and functional domains targeted by the intervention.

PMID- 21169861
TI  - Spanish, French, and British cross-cultural validation of the European Brain
      Injury Questionnaire.
AB  - OBJECTIVE: To explore the factor structure of the European Brain Injury
      Questionnaire and to assess the cross-cultural and construct validity of this
      questionnaire by using Rasch analysis. PARTICIPANTS: A total of 366 individuals
      with traumatic brain injury or stroke were recruited from 3 different countries:
      Spain (116 participants), the United Kingdom (110 participants), and France (140
      participants). ANALYSES: We first performed a factor analysis and then applied
      Rasch analysis to the resulting factors to examine construct and cross-cultural
      validity. RESULTS: Three subscales labeled Depressive Mood, Cognitive
      Dysfunction, and Poor Social and Emotional Self-regulation were extracted using
      the factor analysis. In the Rasch analyses, 8 items were removed because of
      misfit and 7 items showed differential item functioning by country. CONCLUSION:
      Rasch analyses showed good fit to the model, unidimensionality, construct
      validity, and good reliability of the 3 European Brain Injury Questionnaire
      subscales. However, only the Depressive and Cognitive subscales showed cross
      cultural validity.

PMID- 21169862
TI  - Chronic stress and fatigue-related quality of life after mild to moderate
      traumatic brain injury.
AB  - OBJECTIVE: To determine relationships among chronic stress, fatigue-related
      quality of life (QOL-F), and related covariates after mild to moderate traumatic
      brain injury (TBI). DESIGN: Observational and cross-sectional. PARTICIPANTS: A
      total of 84 community-dwelling individuals with mild to moderate TBI recruited
      from multiple out patient rehabilitation clinics assessed on average 15 months
      after injury. METHOD: Self-report surveys and chart abstraction. MEASURES:
      Neurofunctional Behavioral Inventory, Perceived Stress Scale-14, Impact of Events
      Scale, McGill Pain Short-form Scale, and modified version of the Fatigue Impact
      Scale. RESULTS: QOL-F was associated with somatic symptoms, perceived situational
      stress, but not with event-related stress (posttraumatic stress disorder
      symptoms) related to index TBI, preinjury demographic, or postinjury
      characteristics. Somatic symptoms and chronic situational stress accounted for
      42% of the variance in QOL-F. CONCLUSIONS: QOL-F in community-dwelling
      individuals with mild to moderate TBI is associated with chronic situational
      stress and somatic symptoms. Symptom management strategies may need to include
      general stress management to reduce fatigue burden and improve quality of life.

PMID- 21169863
TI  - Arterial wave reflection and subclinical left ventricular systolic dysfunction.
AB  - OBJECTIVES: Increased arterial wave reflection is a predictor of cardiovascular
      events and has been hypothesized to be a cofactor in the pathophysiology of heart
      failure. Whether increased wave reflection is inversely associated with left
      ventricular (LV) systolic function in individuals without heart failure is not
      clear. METHODS: Arterial wave reflection and LV systolic function were assessed
      in 301 participants from the Cardiovascular Abnormalities and Brain Lesions
      (CABL) study using two-dimensional echocardiography and applanation tonometry of
      the radial artery to derive central arterial waveform by a validated transfer
      function. Aortic augmentation index (AIx) and wasted energy index (WEi) were used
      as indices of wave reflection. LV systolic function was measured by LV ejection
      fraction (LVEF) and tissue Doppler imaging (TDI). Mitral annulus peak systolic
      velocity (Sm), peak longitudinal strain and strain rate were measured.
      Participants with history of coronary artery disease, atrial fibrillation, LVEF
      less than 50% or wall motion abnormalities were excluded. RESULTS: Mean age of
      the study population was 68.3 +/- 10.2 years (64.1% women, 65% hypertensive). LV
      systolic function by TDI was lower with increasing wave reflection, whereas LVEF
      was not. In multivariate analysis, TDI parameters of LV longitudinal systolic
      function were significantly and inversely correlated to AIx and WEi (P values
      from 0.05 to 0.002). CONCLUSIONS: In a community cohort without heart failure and
      with normal LVEF, an increased arterial wave reflection was associated with
      subclinical reduction in LV systolic function assessed by novel TDI techniques.
      Further studies are needed to investigate the prognostic implications of this
      relationship.

PMID- 21169864
TI  - Angiotensin II differentially modulates cyclooxygenase-2, microsomal
      prostaglandin E2 synthase-1 and prostaglandin I2 synthase expression in
      adventitial fibroblasts exposed to inflammatory stimuli.
AB  - AIMS: To assess whether angiotensin II (Ang II) modulates key enzymes of the
      cyclooxygenase (COX)-2/prostanoid pathway, including prostaglandin E synthase-1
      (mPGES-1) and prostacyclin synthase (PGIS) in rat aortic adventitial fibroblasts
      in the presence or absence of an inflammatory stimulus [interleukin (IL)-1beta].
      METHODS AND RESULTS: Fibroblasts stimulated with IL-1beta (10 ng/ml, 24 h) and/or
      Ang II (0.1 MUmol/l, 24 h) were used. IL-1beta up-regulated COX-2 and mPGES-1
      (protein and mRNA) and increased PGI2 and PGE2 release, without altering PGIS
      protein expression. Ang II did modify neither COX-2 and mPGES-1 expression nor
      prostanoid levels, but it induced PGIS expression. Interestingly, Ang II further
      enhanced IL-1beta-induced COX-2 expression and PGI2 release and concomitantly
      reduced IL-1beta-induced mPGES-1 expression. The AT1 receptor antagonist losartan
      prevented the effects of Ang II on IL-1beta-induced COX-2 or mPGES-1 expression.
      IL-1beta activated p38 mitogen-activated protein kinase (MAPK) and extracellular
      signal-regulated kinase (ERK)1/2 pathways, and coincubation with Ang II resulted
      in a higher and more sustained phosphorylation of both MAPK. Inhibition of either
      p38 MAPK (SB203580) or ERK1/2 (PD98059) reduced COX-2 and mPGES-1 expression in
      cells treated with IL-1beta or the combination of IL-1beta and Ang II. Ang II did
      not modify COX-2 transcriptional activity but increased COX-2 mRNA stability in
      IL-1beta-treated cells; by contrast, it increased PGIS mRNA levels through a
      transcriptional mechanism. CONCLUSION: Ang II differentially modulates key
      enzymes involved in prostanoid biosynthesis thereby altering the balance between
      PGI2/PGE2 in vascular cells exposed to inflammatory stimuli.

PMID- 21169865
TI  - Procedural and temporal compliance to cervical cancer screening guidelines in a
      CDC-funded program in Alaska.
AB  - OBJECTIVE: To estimate changes in clinical practice in a cervical cancer
      screening program after the American Society for Colposcopy and Cervical
      Pathology's issuance of 2006 consensus guidelines (2006CG) for managing abnormal
      Pap tests. METHODS: Screening and diagnostic procedure records were extracted
      from the operational database of a Centers for Disease Control and Prevention
      funded cervical cancer screening program in Alaska. New software was developed to
      compare these records to the American Society for Colposcopy and Cervical
      Pathology algorithms. Of the 16 algorithms, 11 were encoded, and results of
      patients with abnormal Pap results in 2 study windows (cohort A: 2005-2006: n =
      1,431; cohort B: October 2007 to September 2008: n = 1,369) were compared with
      2006CG recommendations. Comparisons between the practices in the 2 study windows
      were made using the Fisher exact test. RESULTS: Among adolescents with low-grade
      squamous intraepithelial lesion or atypical squamous cells of undetermined
      significance Pap results, 117 (48%) of 243 in cohort A were given colposcopies
      compared with 28 (23%) of 192 in cohort B (p < .0001). There was no difference in
      the rate of human papillomavirus testing between cohorts A and B (23% vs 26%, p =
      .449). Among adults with low-grade squamous intraepithelial lesion, 63 (16%) of
      402 in cohort A were given repeat Pap tests instead of colposcopies compared with
      25 (7%) of 367 in cohort B (p < .0001). Temporal compliance was significantly
      improved (p = .025), with 75% in cohort A and 91% in cohort B being graded as
      timely or early. CONCLUSIONS: Clinical practice has moved toward 2006CG
      recommendations in this program, although gaps remain. This evaluation will be
      used to inform a compliance improvement program. The software can be easily
      modified as 2006CG evolves and can be ported to other algorithmic practice
      guidelines.

PMID- 21169866
TI  - Cervical biopsy sampling variability in ALTS.
AB  - OBJECTIVE: To determine histologic sampling variability among clinical center
      colposcopists and quality control reviewers in the Atypical Squamous Cells of
      Undetermined Significance/Low-grade Squamous Intraepithelial Lesion Triage Study.
      MATERIALS AND METHODS: Clinical center colposcopists and quality control
      reviewers independently indicated need for biopsy, number of biopsies needed, and
      optimal biopsy location on customized computer software and digitized colposcopic
      images while examining subjects or monitoring colposcopists in the Atypical
      Squamous Cells of Undetermined Significance/Low-grade Squamous Intraepithelial
      Lesion Triage Study. Results were compared using percentages of agreement, kappa
      statistics, McNemar, and paired t tests. RESULTS: Colposcopists and reviewers
      agreed whether a cervical biopsy was indicated for 2,631 (72.9%) of 3,610
      evaluable subjects and 415 (91.6%) of 453 subjects with cervical intraepithelial
      neoplasia 2 or worse by histologic diagnosis. Only 3 of 41 colposcopists
      indicated 20% or greater of their biopsy sites to be more than 10 mm from
      reviewers' recommended sites. The mean of the greatest colposcopist-to-reviewer
      biopsy site distance was significantly greater than the mean maximum distance
      between reviewers' biopsy sites (14.9 vs 12.2 mm, p < .0001, respectively).
      Colposcopists indicated a significantly greater number of biopsy sites compared
      with consensus of reviewers (p < .0001). CONCLUSIONS: When cervical cancer
      precursors are present in women with minor cytologic abnormalities, most
      colposcopists obtain a biopsy. However, biopsy site placement can vary
      considerably. Only a minority of colposcopists sample significantly beyond
      recommended areas and less biopsy site variability occurs among experts.

PMID- 21169867
TI  - Indication and outcome of repeat large loop excision biopsies of the cervix.
AB  - INTRODUCTION: To investigate the indications for performing a second large loop
      excision of the transformation zone (LLETZ) biopsy and to compare the associated
      colposcopic and pathological findings and treatment morbidity compared with 1
      LLETZ. METHODS: This is a case-control study that reviewed case notes and
      histology reports on women who had undergone 1 LLETZ biopsy (control group) and
      women who had undergone 2 biopsies (index group). A comparison of referral
      cytology, colposcopic findings, and pathological and clinical outcomes was
      performed. RESULTS: Of the women who went on to have 2 LLETZ biopsies, 88% had
      histologically proven high-grade cervical intraepithelial neoplasia (CIN) or
      invasion on their first biopsy. A significantly greater proportion of high-grade
      cytologic and histologic diagnoses were associated with the first LLETZ compared
      with the second LLETZ biopsy, 76.5% and 69.1% versus 39.5% and 30.9%,
      respectively. A significantly greater proportion of women in the control group
      were referred with low-grade cytology (28.0%) and were diagnosed with human
      papillomavirus/low-grade CIN on histology (31.7%) compared with the first
      cytologic and LLETZ results in the index group, 9.9% and 8.6%, respectively.
      Complications were low in both groups; the immediate complication rate was 4%
      after the first LLETZ compared with 1% after the second LLETZ. CONCLUSIONS: Most
      second LLETZ biopsies are performed in women with a history of biopsy-proven high
      grade CIN and are not associated with an increased risk of immediate
      complications.

PMID- 21169869
TI  - Superficial granulomatous pyoderma of the vulva in a patient receiving
      maintenance rituximab (MabThera) for lymphoma.
AB  - BACKGROUND: Vulval ulceration can be caused by a wide variety of etiological
      factors including bacterial and viral infections, granulomatous disorders, and
      malignancy. Superficial granulomatous pyoderma (SGP) is a variant of pyoderma
      gangrenosum. It is characterized by localized ulcerative lesions that may be
      precipitated by surgery. We report a case of vulval SPG in an immunocompromised
      patient. CASE: A 51-year-old woman presented with a 6-week history of severe
      vulval pain, bleeding, and rapidly progressing ulceration. She had a previous
      history of relapsed follicular non-Hodgkin lymphoma and was currently receiving
      regular MabThera (Welwyn Garden City, Hertfordshire, UK). Examination revealed
      deep ulceration involving the entire vulva and extending into the vagina with
      areas of necrosis. Histological examination showed ulceration with sparse
      granulomas and eosinophils. The clinical and histological findings confirmed a
      diagnosis of SGP. CONCLUSIONS: Vulval ulceration in an immunocompromised patient
      has a broad differential diagnosis. The possibility of a granulomatous condition
      such as SGP must always be considered.

PMID- 21169868
TI  - Association of human papillomavirus-related knowledge, attitudes, and beliefs
      with HIV status: a national study of gay men.
AB  - OBJECTIVE: Anal cancer and other diseases caused by human papillomavirus (HPV)
      are more common among people who are HIV-positive. To understand the potential
      role of HIV status in HPV prevention efforts, we examined HPV-related knowledge,
      attitudes, and beliefs among HIV-positive and HIV-negative gay men. MATERIALS AND
      METHODS: In January 2009, we interviewed a national sample of 247 adult gay men
      from the United States that included an oversample of HIV-positive men. RESULTS:
      Status of HIV was not associated with most beliefs about HPV-related diseases
      (i.e., genital warts, oral cancer, and anal cancer); however, HIV-positive men
      had higher worry about and perceived likelihood of these diseases. Most men
      correctly believed that HIV increases risk of HPV-related diseases, yet 29% to
      42% still did not. Relatively few men believed that HPV vaccine works in males or
      that physicians are allowed to give it to men. Acceptability of the HPV vaccine
      was high and not associated with HIV status (78% of HIV-positive men vs 74% of
      HIV-negative men; adjusted odds ratio = 1.48; 95% confidence interval = 0.67
      3.27). CONCLUSIONS: The high acceptability of HPV vaccine, relatively low
      knowledge of how HIV increases risk for HPV-related diseases, and misperceptions
      about HPV vaccine can inform HPV prevention efforts for gay men. The few
      differences by HIV status suggest that HPV prevention programs may be able to use
      similar approaches with both HIV-negative and HIV-positive gay men.

PMID- 21169870
TI  - Pelvic computed tomography scans for surveillance in patients with primary
      melanoma in the head and neck.
AB  - Although pelvic computed tomography (CT) scans are frequently performed as a part
      of routine surveillance, the evidence for or against the routine use of these
      scans in patients with primary melanoma in the head and neck is weak. We
      conducted a retrospective study to evaluate the value of pelvic CT scans as
      routine surveillance in patients with primary melanoma in the head and neck. We
      identified 146 patients with either primary or mucosal primary melanoma who had
      adequate follow-up evaluation for at least 5 years at our institution. Among
      them, 33 patients (23%) had stage III melanoma, and four (3%) had stage IV
      melanoma at the time of diagnosis. At a median follow-up duration of 49 months,
      110 patients (75%) had developed recurrences, and the median time to the first
      recurrence was 13 months. A total of 82 (56%) patients had eventually developed
      distant metastases, but only 10 (7%) had developed metastases in the pelvis, and
      none had developed pelvic metastases as the first and the only site of
      recurrence. If the true rate of finding the pelvic metastasis as the first and
      the only recurrence was at least 3%, the probability of seeing 0 events of the
      146 patients was 1.17%. This study, which is the largest series to evaluate the
      value of pelvic CT scans in this patient population to date, suggests that the
      routine use of a pelvic CT scan as a surveillance method does not have any impact
      on the management in patients with primary melanoma in the head and neck.

PMID- 21169871
TI  - Phase I dose finding study of carboplatin, paclitaxel, and temozolomide in
      advanced solid tumors.
AB  - This phase I study was carried out to evaluate the optimal dose of temozolomide
      in combination with carboplatin and paclitaxel in patients with advanced solid
      tumors. Patients with advanced melanoma or small cell lung cancer that could
      benefit from the combination of carboplatin and paclitaxel were eligible. A
      standard 3+3 patient cohort dose escalation design was used. Paclitaxel and
      carboplatin were administered at fixed doses of 175 mg/m on day 1 and an area
      under the curve of 5, respectively. Temozolomide was administered at a dose of 75
      mg/m/day from days 2-6 and subsequent cohorts were dose escalated by 25 mg/m
      increments. Cycles were repeated every 28 days. The primary objective of this
      study was to determine the maximum tolerated dose of this combination. Fourteen
      patients were enrolled and 12 patients were evaluable for toxicity and response
      (six with melanoma and six with small cell lung cancer). The maximum tolerated
      dose of temozolomide was 125 mg/m, with fixed doses of carboplatin and
      paclitaxel. There were no treatment delays nor dose reductions at this level.
      There were two partial responses and two patients with stable disease in the
      melanoma group. Four patients had a partial response, and one had stable disease
      in the small cell lung cancer group. There were sustained responses in three of
      the four patients with melanoma who achieved a clinical benefit. In conclusion,
      the combination of carboplatin, paclitaxel, and temozolomide is well tolerated
      and warrants further study. 

PMID- 21169872
TI  - Literate humans sound out words during silent reading.
AB  - Whether humans spontaneously sound out words in their mind during silent reading
      is a matter of debate. Some models of reading postulate that skilled readers
      access the meaning directly from print but others involve print-to-sound
      transcoding mechanisms. Here, we provide evidence that silent reading activates
      the sound form of words before accessing their meaning by comparing event-related
      potentials induced by highly expected words and their homophones. We found that
      expected words and words that sound the same but have a different orthography
      (homophones and pseudohomophones) reduce scalp activity to the same extent within
      300 ms of presentation compared with unexpected words. This shows that
      phonological access during silent reading, which is critical for literacy
      acquisition, remains active in adulthood.

PMID- 21169873
TI  - Features of large cell transformation of indolent lymphomas as observed on
      sequential PET/CT.
AB  - OBJECTIVE: Detection of large cell transformation (LCT) has been reported with
      the increasing use of PET/computed tomography (CT) in patients with indolent
      lymphomas. However, there is little information on PET/CT characteristics,
      specifically, the distribution of lesion maximum standardized uptake value
      (SUV(max)) within a patient, or SUV(max) changes before and after LCT. Our
      objectives were to compare SUV(max) values and distribution between
      nontransformed and LCT patients; to compare SUV(max) of LCT and nontransformed
      lesions in patients with documented focal transformation; and to measure the
      SUV(max) changes in patients before and after LCT. METHODS: Retrospective study
      of patients with LCT (n=29)compared with nontransformed (n=41), and comparison of
      LCT and nontransformed lesions within patients and over time. RESULTS: On
      average, the highest SUV(max) was greater in LCT patients than in nontransformed
      patients. In addition, there was a wider range of SUV(max) values in the LCT
      group compared with the nontransformed group (P<0.05). The median ratio of the
      SUV(max) of 12 LCT to nontransformed biopsy-proven lesions in the same patient
      was 4.3, P value of less than 0.05 (range 2.6-15.5). In 10 of 12 patients it was
      greater than or equal to 3. No change in highest SUV(max) and distribution was
      shown on serial PET in untreated nontransformed patients. CONCLUSION: LCT is
      often focal and is associated with higher SUV(max) than nontransformed. The
      emergence of a focus with SUV(max) three times or higher than others on a single
      scan, or that has tripled or more in value on serial scans, should raise
      suspicion for LCT.

PMID- 21169874
TI  - Goji berry effects on macular characteristics and plasma antioxidant levels.
AB  - PURPOSE: Goji berry (Lycium barbarum L.) is purported to benefit vision because
      of its high antioxidant (especially zeaxanthin) content, although this effect has
      not been demonstrated in high-quality human studies. The purpose of this study
      was to evaluate the effects of daily supplementation with a proprietary milk
      based formulation of goji berry, Lacto-Wolfberry (LWB), on macular
      characteristics and plasma zeaxanthin and antioxidant capacity levels in elderly
      subjects. METHODS: This was a double-masked, randomized, placebo-controlled trial
      in healthy elderly subjects (range, 65 to 70 years) receiving 13.7 g/d of LWB (n
      = 75) or placebo (n = 75) for 90 days. Subjects underwent direct ophthalmic
      examination to assess pigmentation and soft drusen count in the macula and a
      blood draw to measure plasma zeaxanthin level and total antioxidant capacity.
      RESULTS: The placebo group demonstrated hypopigmentation and soft drusen
      accumulation in the macula, whereas the LWB group remained stable. Both plasma
      zeaxanthin level and antioxidant capacity increased significantly in the LWB
      group, by 26% and 57%, respectively, but did not change in the placebo group. No
      product-related adverse events were reported in either group. CONCLUSIONS:
      Overall, daily dietary supplementation with goji berry for 90 days increases
      plasma zeaxanthin and antioxidant levels as well as protects from
      hypopigmentation and soft drusen accumulation in the macula of elderly subjects.
      However, the mechanism of action is unclear, given the lack of relationship
      between change in plasma zeaxanthin and change in macular characteristics.

PMID- 21169875
TI  - A compact clinical instrument for quantifying suppression.
AB  - PURPOSE: We describe a compact and convenient clinical apparatus for the
      measurement of suppression based on a previously reported laboratory-based
      approach. In addition, we report and validate a novel, rapid psychophysical
      method for measuring suppression using this apparatus, which makes the technique
      more applicable to clinical practice. METHODS: By using a Z800 dual pro head
      mounted display driven by a MAC laptop, we provide dichoptic stimulation. Global
      motion stimuli composed of arrays of moving dots are presented to each eye. One
      set of dots move in a coherent direction (termed signal) whereas another set of
      dots move in a random direction (termed noise). To quantify performance, we
      measure the signal/noise ratio corresponding to a direction-discrimination
      threshold. Suppression is quantified by assessing the extent to which it matters
      which eye sees the signal and which eye sees the noise. RESULTS: A space-saving,
      head-mounted display using current video technology offers an ideal solution for
      clinical practice. In addition, our optimized psychophysical method provided
      results that were in agreement with those produced using the original technique.
      We made measures of suppression on a group of nine adult amblyopic participants
      using this apparatus with both the original and new psychophysical paradigms. All
      participants had measurable suppression ranging from mild to severe. The two
      different psychophysical methods gave a strong correlation for the strength of
      suppression (rho = -0.83, p = 0.006). CONCLUSION: Combining the new apparatus and
      new psychophysical method creates a convenient and rapid technique for parametric
      measurement of interocular suppression. In addition, this apparatus constitutes
      the ideal platform for suppressors to combine information between their eyes in a
      similar way to binocularly normal people. This provides a convenient way for
      clinicians to implement the newly proposed binocular treatment of amblyopia that
      is based on antisuppression training.

PMID- 21169876
TI  - Ocular components in three breeds of dogs with high prevalence of myopia.
AB  - PURPOSE: Experimental models of human myopia have been developed using animals of
      various species. However, most of these are an induced rather than a spontaneous,
      naturally occurring myopia. This study was conducted to evaluate whether the
      spontaneous myopia found in three canine breeds was axial in nature and therefore
      similar to humans. METHODS: Refractive error was measured by cycloplegic
      retinoscopy and ocular components by A-scan ultrasound (ocular axial dimensions)
      and videophakometry (corneal and lens radii and powers) in 83 dogs of three
      breeds [English Springer Spaniels (n = 33), Toy Poodles (n = 36), and Collies (n
      = 14)]. Dogs with refractive errors equal to or more myopic than -0.5 diopters
      spherical equivalent were considered myopic. RESULTS: Myopia was most common in
      Toy Poodles (63.9%), followed by English Springer Spaniels (36.4%) and Collies
      (35.7%). Axial lengths and vitreous chamber depths were not different between
      myopic and non-myopic dogs (p = 0.84 and 0.63, respectively). The anterior
      crystalline lens radius was steeper and the lens power was greater in myopic
      compared with non-myopic dogs (p = 0.048 for each). CONCLUSIONS: Spontaneous
      myopia was very common in all three breeds in this sample of dogs, with Toy
      Poodles being most affected. However, the cause of the myopia appeared to be
      refractive, that is from a steeper, more powerful crystalline lens, rather than
      from excess axial elongation. These breeds do not appear to be promising models
      for human axial myopia.

PMID- 21169877
TI  - Semiautomatic extraction algorithm for images of the ciliary muscle.
AB  - PURPOSE: To develop and evaluate a semiautomatic algorithm for segmentation and
      morphological assessment of the dimensions of the ciliary muscle in Visante
      Anterior Segment Optical Coherence Tomography images. METHODS: Geometric
      distortions in Visante images analyzed as binary files were assessed by imaging
      an optical flat and human donor tissue. The appropriate pixel/mm conversion
      factor to use for air (n = 1) was estimated by imaging calibration spheres. A
      semiautomatic algorithm was developed to extract the dimensions of the ciliary
      muscle from Visante images. Measurements were also made manually using Visante
      software calipers. Interclass correlation coefficients and Bland-Altman analyses
      were used to compare the methods. A multilevel model was fitted to estimate the
      variance of algorithm measurements that was due to differences within- and
      between-examiners in scleral spur selection vs. biological variability. RESULTS:
      The optical flat and the human donor tissue were imaged and appeared without
      geometric distortions in binary file format. Bland-Altman analyses revealed that
      caliper measurements tended to underestimate ciliary muscle thickness at 3 mm
      posterior to the scleral spur in subjects with the thickest ciliary muscles (t =
      3.6, p < 0.001). The percent variance due to within- or between-examiner
      differences in scleral spur selection was found to be small (6%) when compared
      with the variance because of biological difference across subjects (80%). Using
      the mean of measurements from three images, achieved an estimated interclass
      correlation coefficient of 0.85. CONCLUSIONS: The semiautomatic algorithm
      successfully segmented the ciliary muscle for further measurement. Using the
      algorithm to follow the scleral curvature to locate more posterior measurements
      is critical to avoid underestimating thickness measurements. This semiautomatic
      algorithm will allow for repeatable, efficient, and masked ciliary muscle
      measurements in large datasets.

PMID- 21169878
TI  - Prediction of pancreatic tissue densities by an analytical test gradient system
      before purification maximizes human islet recovery for islet
      autotransplantation/allotransplantation.
AB  - BACKGROUND: Using standard density gradient (SDG) ranges for human islet
      purification frequently results in islet loss and transplantation of lower islet
      mass. Measuring the densities of islet and acinar tissue beforehand to customize
      the gradient range for the actual COBE 2991 cell processor (COBE) purification is
      likely to maximize the recovery of islets. We developed an analytical test
      gradient system (ATGS) for predicting pancreatic tissue densities before COBE
      purification to minimize islet loss during purification. METHODS: Human islets
      were isolated from deceased donor (n=30) and chronic pancreatitis pancreata
      (n=30). Pancreatic tissue densities were measured before purification by the
      ATGS, and the density gradient range for islet purification in a COBE was
      customized based on density profiles determined by the ATGS. The efficiency of
      custom density gradients (CDGs) to recover high islet yield was compared with
      predefined SDGs. RESULTS: Pancreatic tissue densities from autografts were
      significantly higher than in allograft preparations. In allograft purifications,
      a higher proportion of islets were recovered using ATGS-guided CDGs (85.9%+/
      18.0%) compared with the SDG method (69.2%+/-27.0%; P=0.048). Acinar
      contamination at 60%, 70%, and 80% cumulative islet yield for allografts was
      significantly lower in the CDG group. In autograft purifications, more islets
      were recovered with CDGs (81.9%+/-28.0%) than SDGs (55.8%+/-22.8%; P=0.03). CDGs
      effectively reduced islet loss by minimizing islet sedimentation in the COBE bag.
      CONCLUSIONS: Using ATGS-guided CDGs maximizes the islet recovery for successful
      transplantations by reducing acinar contamination in allograft preparations and
      by reducing sedimentation of islets in the COBE bag in autograft preparations.

PMID- 21169879
TI  - Equivalent neurogenic potential of wild-type and GFP-labeled fetal-derived neural
      progenitor cells before and after transplantation into the rodent hippocampus.
AB  - INTRODUCTION: The hippocampal formation is a specific structure in the brain
      where neurogenesis occurs throughout adulthood and in which the neuronal cell
      loss causes various demential states. The main goal of this study was to verify
      whether fetal neural progenitor cells (NPCs) from transgenic rats expressing
      green fluorescent protein (GFP) retain the ability to differentiate into neuronal
      cells and to integrate into the hippocampal circuitry after transplantation.
      METHODS: NPCs were isolated from E14 (gestational age: 14 days postconception)
      transgenic-Lewis and wild-type Sprague-Dawley rat embryos. Wild-type and
      transgenic cells were expanded and induced to differentiate into a neuronal
      lineage in vitro. Immunocytochemical and electrophysiological analysis were
      performed in both groups. GFP-expressing cells were implanted into the
      hippocampus and recorded electrophysiologically 3 months thereafter.
      Immunohistochemical analysis confirmed neuronal differentiation, and the yield of
      neuronal cells was determined stereologically. RESULTS: NPCs derived from wild
      type and transgenic animals are similar regarding their ability to generate
      neuronal cells in vitro. Neuronal maturity was confirmed by immunocytochemistry
      and electrophysiology, with demonstration of voltage-gated ionic currents, firing
      activity, and spontaneous synaptic currents. GFP-NPCs were also able to
      differentiate into mature neurons after implantation into the hippocampus, where
      they formed functional synaptic contacts. CONCLUSIONS: GFP-transgenic cells
      represent an important tool in transplantation studies. Herein, we demonstrate
      their ability to generate functional neurons both in vitro and in vivo
      conditions. Neurons derived from fetal NPCs were able to integrate into the
      normal hippocampal circuitry. The high yield of mature neurons generated render
      these cells important candidates for restorative approaches based on cell
      therapy.

PMID- 21169880
TI  - Introducing hand-assisted retroperitoneoscopic live donor nephrectomy: learning
      curves and development based on 413 consecutive cases in four centers.
AB  - BACKGROUND: Hand-assisted and retroperitoneoscopic techniques reduce the risk of
      bleeding and intraabdominal complications in living donor nephrectomy (LDN). This
      study reports on our four-center experience, development, and learning curves
      from the first 413 LDNs using a hand-assisted retroperitoneoscopic (HARS)
      technique. METHODS: The first 413 consecutive donors operated on using HARS were
      included in the study. Donor demographics, perioperative and postoperative data,
      complications, and recipient outcomes have been compiled. The data were analyzed
      as a whole and separately for each center, looking at center differences and
      learning curves over time. RESULTS: Significant differences were found in donor
      demographics between centers for the variables: age, body mass index, number of
      arteries, and side of operation. Mean operating time was 170.2 min, with
      significant differences between centers. Operating time was also significantly
      influenced by learning curves, sex/body mass index, and side of operation. Warm
      ischemia time differed significantly between centers and was influenced by center
      wise learning and number of arteries. Overall conversion rate was 2.4% and
      differed significantly between centers. There was no mortality and no
      intraabdominal complications. Apart from the conversions and one pulmonary
      embolism, there were no major intraoperative or postoperative complications.
      Overall 3-month graft survival was 99%, with 96% immediate onset of function and
      1% ureteral complications. CONCLUSIONS: The HARS technique reduces the risk of
      intraabdominal complications. It can be implemented with excellent donor and
      recipient outcomes despite different population demographics and center/surgeon
      related tradition and experience. On the basis of our experience, we recommend
      the technique to increase the safety margin of LDN.

PMID- 21169881
TI  - Universal prophylaxis is cost effective in cytomegalovirus serology-positive
      kidney transplant patients.
AB  - BACKGROUND: The economic merit of universal prophylaxis and preemptive therapy in
      the management of cytomegalovirus (CMV) infection for serology positive (R+)
      kidney transplant patients remains undefined. We performed cost effectiveness and
      cost utility modeling comparing these two approaches. METHODS: The incidence of
      CMV infection under universal prophylaxis and preemptive therapy was determined
      among 653 R+ patients from our institution and 416 R+ patients from various
      clinic trials, respectively. Standardized decision tree analysis and Markov
      transitional models were used to calculate cost and quality-adjusted life years
      (QALYs) from the prototypical clinical data and published literature. Incremental
      cost effectiveness and cost utility were calculated as dollars for one case of
      infection avoided and one QALY gained over 10 years, respectively. One- and two
      way sensitivity analyses were performed. RESULTS: The incidence of CMV infection
      was 4.1% and 55.5% within the first year after transplant for universal
      prophylaxis and preemptive therapy, respectively. Compared with preemptive
      therapy, universal prophylaxis incurred $1464 more in direct cost while saving
      $7309 in indirect cost, and resulted in a net gain of 0.209 in QALYs per patient
      over a 10-year period. Thus, universal prophylaxis dominates over preemptive
      therapy with a cost saving of $27,967 for 1 QALY gained. This cost saving was
      sensitive to the variation in the rate of CMV infection and disease with each
      approach. CONCLUSION: Universal prophylaxis in CMV R+ kidney transplant patients
      is clinically effective and cost saving. It should be considered as the preferred
      approach.

PMID- 21169883
TI  - The influence of mixed activators on ethylene polymerization and ethylene/1
      hexene copolymerization with silica-supported Ziegler-Natta catalyst.
AB  - This article reveals the effects of mixed activators on ethylene polymerization
      and ethylene/1-hexene copolymerization over MgCl2/SiO2-supported Ziegler-Natta
      (ZN) catalysts. First, the conventional ZN catalyst was prepared with SiO2
      addition. Then, the catalyst was tested for ethylene polymerization and
      ethylene/1-hexene (E/H) co-polymerization using different activators.
      Triethylaluminum (TEA), tri-n-hexyl aluminum (TnHA) and diethyl aluminum chloride
      (DEAC), TEA+DEAC, TEA+TnHA, TnHA+ DEAC, TEA+DEAC+TnHA mixtures, were used as
      activators in this study. It was found that in the case of ethylene
      polymerization with a sole activator, TnHA exhibited the highest activity among
      other activators due to increased size of the alkyl group. Further investigation
      was focused on the use of mixed activators. The activity can be enhanced by a
      factor of three when the mixed activators were employed and the activity of
      ethylene polymerization apparently increased in the order of TEA+ DEAC+TnHA >
      TEA+DEAC > TEA+TnHA. Both the copolymerization activity and crystallinity of the
      synthesized copolymers were strongly changed when the activators were changed
      from TEA to TEA+DEAC+TnHA mixtures or pure TnHA and pure DEAC. As for ethylene/1
      hexene copolymerization the activity apparently increased in the order of
      TEA+DEAC+TnHA > TEA+TnHA > TEA+DEAC > TnHA+DEAC > TEA > TnHA > DEAC. Considering
      the properties of the copolymer obtained with the mixed TEA+DEAC+TnHA, its
      crystallinity decreased due to the presence of TnHA in the mixed activator. The
      activators thus exerted a strong influence on copolymer structure. An increased
      molecular weight distribution (MWD) was observed, without significant change in
      polymer morphology.

PMID- 21169882
TI  - Antioxidant activity of lignin phenolic compounds extracted from kraft and
      sulphite black liquors.
AB  - The antioxidant activity of the phenolic compounds present in industrial black
      liquors obtained from the two cooking processes (kraft and sulphite) used in
      Portugal to produce Eucalyptus globulus pulp was evaluated. The black liquors
      treated at several pH values were extracted with ethyl acetate. Phenolic
      fractions were further separated by liquid chromatography of the crude extracts
      of kraft liquor at pH = 6 and sulphite liquor at the original pH. Total phenolic
      content was determined in terms of gallic acid equivalents (Folin-Ciocalteu
      colorimetric method), and the antioxidant activity in the crude extracts at
      several pH values and in the separated fractions was measured using the DPPH test
      for radical scavenging capacity. The total phenolic content of crude extracts and
      separated fractions ranged from 92.7 to 181.6 and from 91.6 to 1,099.6 mg GAE/g,
      respectively, while the antioxidant activity index (AAI) ranged from 2.20 to 3.41
      and from 2.21 to 11.47 respectively, showing very strong antioxidant activity in
      all studied cases. The fractions separated by column chromatography were
      submitted to mass spectrometry analysis and the results were compared to others
      in the literature of natural products, mainly from Eucalyptus, and the
      characteristic bands of functional groups were identified by 1H-NMR and FTIR.
      These methods allowed the identification of 17 phenolic compounds.

PMID- 21169885
TI  - Molecular modeling studies on 11H-dibenz[b,e]azepine and
      dibenz[b,f][1,4]oxazepine derivatives as potent agonists of the human TRPA1
      receptor.
AB  - A computational strategy based on comparative molecular fields analysis (CoMFA)
      and comparative molecular similarity indices analysis (CoMSIA) was performed on a
      series of the 11H-dibenz[b,e]azepine and dibenz[b,f][1,4]oxazepine derivatives as
      potent agonists of the human TRPA1 receptor. The CoMFA and CoMSIA models
      resulting from a 21 molecule training set gave r2(cv) values of 0.631 and 0.542
      and r2 values of 0.986 and 0.981, respectively. The statistically significant
      models were validated by a test set of five compounds with predictive r2(pred).
      values of 0.967 and 0.981 for CoMFA and CoMSIA, respectively. A systemic external
      validation was also performed on the established models. The information obtained
      from 3D counter maps could facilitate the design of more potent human TRPA1
      receptor agonists.

PMID- 21169886
TI  - Neurons on the couch.
AB  - A hundred years after psychoanalysis was introduced, neuroscience has taken a
      giant step forward. It seems nowadays that effects of psychotherapy could be
      monitored and measured by state-of-the art brain imaging techniques. Today, the
      psychotherapy is considered as a strategic and purposeful environmental influence
      intended to enhance learning. Since gene expression is regulated by environmental
      influences throughout life and these processes create brain architecture and
      influence the strength of synaptic connections, psychotherapy (as a kind of
      learning) should be explored in the context of aforementioned paradigm. In other
      words, when placing a client on the couch, therapist actually placed client's
      neuronal network; while listening and talking, expressing and analyzing,
      experiencing transference and counter transference, therapist tends to stabilize
      synaptic connections and influence dendritic growth by regulating gene
      transcriptional activity. Therefore, we strongly believe that, in the near
      future, an increasing knowledge on cellular and molecular interactions and
      mechanisms of action of different psycho- and pharmaco-therapeutic procedures
      will enable us to tailor a sophisticated therapeutic approach toward a person, by
      combining major therapeutic strategies in psychiatry on the basis of rational
      goals and evidence-based therapeutic expectations.

PMID- 21169884
TI  - Evaluation of the bioactivity of novel spiroisoxazoline typecompounds against
      normal and cancer cell lines.
AB  - The aim of this study was to investigate the in vitro cellular activity of novel
      spiroisoxazoline type compounds against normal and cancer cell lines from lung
      tissue (Hs888Lu), neuron-phenotypic cells (SH-SY5Y), neuroblastoma (SH-SY5Y),
      human histiocytic lymphoma (U937), lung cancer (A549), and leukaemia (HL-60). Our
      bioassay program revealed that the spiroisoxazoline type compounds show
      cytotoxicity only in lymphoma cell lines, which is in contrast with the
      pyrrolidine precursor of these spiroisoxazoline compounds, where significant
      cytotoxicity is seen in all normal and cancer cell lines. These data suggest a
      tumour-specific mechanism of action. In addition these data also show that
      spiroisoxazoline compounds are non-toxic in the human neuronphenotypic
      neuroblastoma SH-SY5Y cell line, and furthermore that they might protect cells
      from neurodegenerative disease.

PMID- 21169887
TI  - Critical review of studies on quality of life in psychiatric patients published
      in Serbian medical journals from 2000 to 2009.
AB  - BACKGROUND: Quality of life (QoL) is known to be indicative of the level of
      social functioning in mental health patients. However, the research on QoL, in
      the field of psychiatry, is not as comprehensive as it is in other domains of
      medicine. The aim of this study was to review the research evidence on QoL in
      psychiatric patients, published in Serbian medical journals during the last
      decade. MATERIAL AND METHODS: The research data from studies on quality of life
      in psychiatric patients, published in Serbian medical journals from 2000 to 2009,
      were obtained by searching the databases Kobson and Medline. RESULTS: We found
      eight studies on QoL in psychiatric patients published in Serbian medical
      journals from 2000 to 2009. The reviewed articles were focused on the comparison
      of QoL between psychiatric patients and healthy controls, or somatic patients,
      the research on the relationship of QoL and general psychopathology, and the
      research on QoL and medical treatment. CONCLUSIONS: QoL in patients suffering
      from mental disorders, as the outcome variable, is of a paramount interest in the
      follow-up treatment studies in psychiatry targeting critical issues of mental
      illness management strategies. QoL of psychiatric patients in Serbia is still
      under-researched, and it would be important to measure QoL from both a patient's
      and observer's (i.e. family members, friends, nursing staff, mental health
      professionals, etc.) perspective, in the context of social, economic, and
      cultural background of the patient. In the future, the studies on QoL in
      psychiatric patients in Serbia should also rely on "disease specific" assessment
      scales, which would consider particular aspects of psychopathology, and
      eventually follow up longitudinal course of mental illness, treatment outcome,
      and recovery.

PMID- 21169888
TI  - Antipsychotics and the quality of life of schizophrenic patients.
AB  - Patients' attitudes and values, their concept of illness and health as well as
      their previous experiences with medication may significantly affect the
      subjective response to antipsychotics. Quality of Life (QOL) has holistic concept
      that includes consideration of economic development, social vitality and
      environmental health. For most of the researches, QOL has an umbrella concept,
      which covers all aspects of life and includes physical and mental health, family
      relations, friendship, employment, leisure activities, medical treatment and
      quality of care, psychological and social benefit. In the domain of mental
      health, increasing the quality of treatment can be demonstrated through
      improvements of QOL of those using the mental health services. When measuring QOL
      in patients taking antipsychotics, it is important to acknowledge that a variety
      of factors may influence the QOL outcomes: these include side effects and daily
      dosage of the antipsychotic, depressive and negative symptoms, duration of
      treatment, and subjective tolerability.

PMID- 21169889
TI  - Object and subject relations in adulthood--towards an integrative model of
      interpersonal relationships.
AB  - In the article the author presents a model of interpersonal relationships based
      on integration of object relations theory and theory of attachment. He proposes
      three main bipolar dimensions of interpersonal relationships: Independence -
      Dependence, Connectedness - Alienation and Reciprocity - Self-absorption. The
      author also proposes that it is important to distinguish between two main types
      of adult interpersonal relationships: object and subject relations. Object
      relations describe relationships in which the other person is perceived as an
      object that serves the satisfaction of the first person's needs. Object relations
      are a manifestation of the right pole of the three main dimensions of
      interpersonal relationships (Dependence, Alienation and Self-absorption). Subject
      relations are a counter-pole to the concept of object relations. They describe
      relationships with other people who are experienced as subjects with their own
      wishes, interests and needs. Subject relations are a manifestation of the left
      pole of the main dimensions (Independence, Connectedness and Reciprocity). In
      this article the author specifically focuses on definitions of object relations
      in adulthood through a description of six sub-dimensions of object relations:
      Symbiotic Merging, Separation Anxiety, Social Isolation, Fear of Engulfment,
      Egocentrism and Narcissism. Every sub-dimension is described in connection to
      adaptive and pathological functioning. Further research is needed to test the
      clinical and scientific validity of the model.

PMID- 21169890
TI  - AD/HD in the genesis of conduct disorder--does biopsychosocial approach make
      sense?
AB  - There are numerous theories approaching the source of mental disorders (including
      conduct disorder) from different perspectives - biological, psychological, social
      and multifactorial. The question that arises is which theory is to be used to
      explain the issue. In the interpretation of phenomena in psychiatry, Kecmanovic
      discusses possibilities of different approaches (biological, psychological,
      social and biopsychosocial models) and concludes that none of them provide a
      complete solution as to how to approach different disorders. The question,
      therefore, is how to proceed? Although according to Kecmanovic, the
      biopsychosocial model, as Engel has formulated it, "provides only ingredients not
      a prescription", it is our opinion that it indeed does not need to provide
      prescriptions- it is sufficient if it indicates the necessary ingredients. The
      prescription itself is to be found in novel scientific disciplines, in particular
      neuropsychology and epigenetics. Gilbert, on the other hand, points out that the
      bio- psychosocial approach is holistic, and more than that. "The bio psychosocial
      approach addresses the complexity of interactions between different domains of
      functioning and argues that it is the interaction of domains that illuminates
      important processes" e.g. a hierarchical dimension of the model as one and
      development as another dimension provide the basis for a comprehensive
      perspective on psychiatric disorders, in this case of AD/HD as a risk factor for
      conduct disorder.

PMID- 21169891
TI  - Autistic spectrum disorders and schizophrenia in the adult psychiatric setting:
      diagnosis and comorbidity.
AB  - BACKGROUND: The relationship between Autism Spectrum Disorders (ASDs) and
      schizophrenia is currently unclear. We aimed to (a) assess psychotic symptoms in
      a consecutive series of adult patients with ASDs, (b) evaluate the comorbidity
      diagnosed to account for the concurrent psychotic symptoms in patients with ASDs,
      and (c) compare the clinical features between the patients with schizophrenia and
      patients with comorbid schizophrenia and ASDs. SUBJECTS AND METHODS: We included
      patients with ASD that were seen in adult psychiatric clinical settings during a
      15-year period. The sample was further grouped according to the existence of a
      comorbid diagnosis of schizophrenia. Clinical and epidemiological features were
      assesed in in the whole sample, and further compared between the two groups.
      RESULTS: We identified 26 patients with first-time diagnosed ASDs. Among the 22
      cases who manifested psychotic symptoms (84.6%), 16 had a concurrent diagnosis of
      schizophrenia (72.73%) and 6 of mood disorders (27.27%). Compared with patients
      with schizophrenia patients with comorbid ASDs and schizophrenia were more often
      men, of younger age, and more frequently developed motor side effects to
      antipsychotics. CONCLUSIONS: Adult psychiatric service users with ASDs are often
      misdiagnosed. This could be in part due to the fact that adult psychiatrists are
      not familiar with the diagnosis of ASDs. The high prevalence of psychotic
      symptoms in this sample is likely to depend on the specific setting of the study,
      i.e., that people with more severe forms of ASD than those typically followed-up
      in the national health service were reaching our public inpatient and private
      outpatient services. The high comorbidity rate between ASDs and schizophrenia
      could be related to shared neurobiology, but also to arbitrary restrictions
      imposed by current diagnostic systems.

PMID- 21169892
TI  - No association between polymorphisms in four serotonin receptor genes, serotonin
      transporter gene and alcohol-related suicide.
AB  - BACKGROUND: Serotonin (5-HT) is an important neurotransmitter with wide-ranging
      functions. Its disfunction in the central nervous system seems to play an
      important role in many psychiatric disorders and suicidal behavior. The objective
      of this study was to examine the association between polymorphisms in different
      serotonin receptor genes (HTR): HTR1A (polymorphism -1019C>G), HTR1B
      (polymorphisms 861G>C and -161A>T), HTR1F (polymorphism -78C>T) and HTR2A
      (polymorphism -1420C>T), and serotonin transporter gene (5-HTT) (polymorphism LPR
      in promoter and VNTR in the second intron), and completed alcohol-related
      suicide, as well as between alcohol-dependent suicide victims. SUBJECTS AND
      METHODS: The study subjects were 373 Slovenian suicide victims (mean age +/- SD:
      48.8 +/- 17.7 years) autopsied in the years 2002 through 2005. During autopsy
      venous blood was drawn, and afterwards DNA extraction and alcoholimetric analysis
      were performed. Relatives of 79 suicide victims were interviewed using a semi
      structured questionnaire designed according to Slovenian cultural and economic
      conditions. They provided information about the alcohol abuse of the suicide
      victims. Amongst the suicide victims were 25 alcohol misusers and 54 non
      misusers. RESULTS: Association between polymorphisms in the selected serotonin
      receptor genes, transporter gene and completed alcohol-related suicide, as well
      as between alcohol-dependent suicide victims was not established. CONCLUSIONS:
      Present results suggest that selected polymorphisms of the 5-HT receptor genes
      and transporter gene are not involved in genetic susceptibility to completed
      suicide under acute influence of alcohol or among alcohol-dependent individuals,
      but further studies in a larger sample are needed.

PMID- 21169893
TI  - Cognitive dysfunction, dissociation and quality of life in bipolar affective
      disorders in remission.
AB  - BACKGROUND: Bipolar disorders are often associated with cognitive deficits, which
      have an influence on social functioning and the course of the illness. These
      deficits have an impact on occupational ability and social integration. SUBJECTS
      AND METHODS: To ascertain cognitive function, level of dissociation and quality
      of life and their interrelations in patients with bipolar affective disorder in
      remission. Data from D2 Attention Test, Verbal Fluency Test and Trial Making
      Test, Dissociative Experiences Scale (DES). Quality of Life Satisfaction and
      Enjoyment (Q-LES-Q) and M.I.N.I. (MINI-international neuropsychiatric interview
      were statistically analyzed. RESULTS: There are no significant correlations
      between applied cognitive tests and dissociation scale DES. There are no
      significant correlations between applied cognitive tests and dissociation scale
      DES. There were no differences between employed and unemployed patients in DES,
      pathological DES and in any of Q-.LES-Q domains. CONCLUSIONS: We need further
      research to explore the role of cognitive functions and dissociation in bipolar
      affective disorder and its relationship to cognitive functions, emotional
      regulation, biological factors and therapy outcome.

PMID- 21169894
TI  - Unaided general practitioners' clinical diagnosis in evaluation of depressive
      patients: a pilot study.
AB  - BACKGROUND: In this study we wished to determine the diagnostic accuracy of
      unaided general practitioners' (GPs') clinical diagnosis in the evaluation of
      depression in depressed patients under their care compared with the Beck
      Depression Inventory II (BDI-II). SUBJECTS AND METHODS: From 17,000 patients in
      10 GPs' offices as representative sample in the city of Zagreb, 5100 patients
      from three GPs' offices were selected. The sample consisted of 53 out of 76
      depressed patients with a diagnosis of Depressive episode (F32) or Recurrent
      depressive disorder (F33) classified according to ICD-10 and assessed by review
      of the GP's standardized medical records. Cross-sectional investigation was
      performed during February 2008. GPs classified depressed patients as either
      nondepressed without therapy, nondepressed with therapy or depressed with
      therapy. Within a two-week period, the unaided GPs' diagnosis was compared with
      BDI-II performed by psychologists unfamiliar with the GPs' assessment. Based on
      the GP vs. BDI-II comparison, patients were classified as either positive, false
      positive, false negative or negative. Sensitivity, specificity, PPV, and NPV
      associated with physician identification of depression were calculated by
      standard methods. RESULTS: Depressiveness was found by BD-II in the group
      'depressed with therapy' (24.39+/-10.91). ANOVA found a significant difference in
      BDI-II means between the outcome groups (P<0.001). Scheffe's procedure found a
      significant difference in BDI-II in patients with therapy (nondepressed vs.
      depressed) (P<0.001) and nondepressed without therapy vs. depressed with therapy
      (P<0.001). There were 16 depressed patients, 27 nondepressed, 2 false positive,
      and 8 false negative. Unaided GPs' clinical diagnosis showed 66% sensitivity,
      93%, specificity, 88% PPV, and 77% NPV. CONCLUSION: Unaided GPs' clinical
      diagnosis with 88% PPV outperforms other measures of patient depression and is
      easier to implement when compared to the psychiatric model of caseness, which is
      based on screening instruments.

PMID- 21169895
TI  - First episode psychosis and treatment delay--causes and consequences.
AB  - INTRODUCTION: According to the clinical perspective, early diagnosis of the
      prodromal phase and early treatment provision in the first episode of psychosis
      (FEP) is able to prevent or reduce morbidity. The main aim of this study is to
      inventory and analyze the most important causes of treatment delay from the
      perspective of patients, families and healthcare providers. The secondary aim is
      to point out the most important consequences of treatment delay. SUBJECTS AND
      METHODS: The study was conducted on 28 patients hospitalized for FEP of a
      schizophrenia spectrum disorder in the Psychiatry Clinic of Timisoara and Day
      care center 2009. The corresponding sample of relatives consisted of 25
      relatives, and the sample of health care providers of 10 general practitioners
      and 11 psychiatrists. A semi-structured interview with open-ended questions was
      used. RESULTS: Data analysis generated the following themes: society's beliefs
      and attitude about mental illness; fear of stigma and labeling, insufficient
      information, lack of infrastructure from the perspective of the professionals,
      and modified threshold for treatment initiation. CONCLUSIONS: Efforts at the
      level of Communities as well as efforts at the level of psychiatry specialists
      could help individuals and their families to overcome the illness situation and
      improve their quality of life.

PMID- 21169896
TI  - The effect of Olanzapine and Sertraline on personality disorder in patients with
      methadone maintenance therapy.
AB  - BACKGROUND: Various drugs have been suggested for treatment of Borderline
      Personality Disorder (BPD)-a disabling disease affecting two percent of the
      general population. If a drug could alleviate a wide range of symptoms, it would
      be more suitable. In these disorders drug addiction is very common. This fact
      makes the symptoms complicated and the treatment more difficult. SUBJECTS AND
      METHODS: This study is designed to evaluate the effect of Olanzapine and
      Sertraline in patients suffering from personality disorders who are on methadone
      maintenance therapy. This study is a clinical trial. 120 males and females were
      chosen for methadone maintenance therapy through interview by a psychiatrist
      based on DSM-IV-TR diagnostic criteria for BPD. Afterwards they were randomly
      divided into two groups. These groups separately received Olanzapine (5-10 mg
      daily) and Sertraline (50-100 mg daily) therapy. The SCL-90 questionnaire was
      filled by all participants before treatment and at the 4th, 8th and 12th weeks of
      treatment. RESULTS: According to this clinical trial, Olanzapine and Sertraline
      are effective in ameliorating symptoms of depression, anxiety and aggression,
      reducing sensitivity in interpersonal relationships and alleviating obsessive
      symptoms, pessimistic behaviors and somatization disorders in patients with
      personality disorders on methadone maintenance therapy. CONCLUSION: As result of
      this study it appears that Olanzapine and Sertraline are definitely effective in
      alleviating symptoms of patients with personality disorder, prescribing theses
      drugs are recommended for these patients.

PMID- 21169897
TI  - Hospital dependency: an existing concept.
AB  - Chronically institutionalized patients demonstrate a behavioral pattern
      characterized by unwillingness to get discharged from the hospital and severe
      anxiety during such attempts leading to continued hospitalization. These patients
      usually have poor self-concept and low evaluation in getting employment, which
      requires vocational rehabilitation. To prevent this, mental health professionals
      should make active efforts to develop a favorable attitude of the chronic
      mentally ill patients towards their home.

PMID- 21169898
TI  - False conclusions regarding duloxetine's purported efficacy in pain among
      depressed patients.

PMID- 21169900
TI  - Modulation of leptin by histamine H1 receptors as a novel therapeutic approach
      for treatment of clozapine induced seizure.

PMID- 21169901
TI  - Carnitine regulates myocardial metabolism by Peroxisome Proliferator-Activated
      Receptor-alpha (PPARalpha) in alcoholic cardiomyopathy.
AB  - BACKGROUND: Chronic alcohol intake exerts myocardial damage en route to the
      development of alcoholic cardiomyopathy (ACM), although the precise pathogenesis
      of ACM is unknown. Carnitine is known to participate in the regulation of
      metabolism in a number of heart diseases. This study was designed to examine the
      interplay between myocardial metabolism and carnitine in the development of ACM.
      MATERIAL/METHODS: Experimental animals were divided into 3 groups: (i) group A:
      alcohol-fed. (ii) group B: alcohol/carnitine: (200mg/kg/d, p.o. by mixing
      carnitine in rat chow). (iii) group C: control. Blood levels of free fatty acid
      (FFA), total carnitine (TC) and free carnitine (FC) were monitored in rats
      receiving alcohol with or without carnitine. Mitochondrial adenine nucleotide
      translocator-1 (ANT1) activity, ATPase activity, high energy phosphate
      concentration, peroxisome proliferator-activated receptor-alpha (PPARalpha),
      carnitine-palmitoyl transferase I (CPT-I), medium-chain acyl-coenzyme A
      dehydrogenase (MCAD), ANT1 and ATPase mRNA and protein expression were also
      monitored in myocardial tissue. RESULTS: Experimental animals received alcohol
      with or without carnitine for six 6 months. Our results indicated that FFA
      increased abruptly. TC and FC were significantly decreased in groups receiving
      alcohol at 4 months. The concentration of ATP, ADP and AMP in the myocardium
      decreased following 2 months of alcohol administration. mRNA and protein
      expression of PPARalpha, CPT-I, MCAD, ANT1 and ATPase expressions were gradually
      altered in groups following alcohol feeding. CONCLUSIONS: These observations
      suggest that abnormal metabolism is present in the myocardium during the
      development of ACM. Carnitine may improve myocardial metabolism by elevating the
      content of PPARalpha, CPT-I and MCAD.

PMID- 21169902
TI  - Experimentally modified Fontan circulation in an adolescent pig model without the
      use of cardiopulmonary bypass.
AB  - BACKGROUND: The feasibility and the hemodynamic outcome of Fontan circulation,
      without the use of cardiopulmonary bypass, were studied on a beating heart of an
      adolescent pig model, using a modified total cavopulmonary connection.
      MATERIAL/METHODS: Eight open-chest anesthetized pigs underwent a successful total
      cavopulmonary connection with the use of an appropriate Y-shaped Dacron-type
      conduit. Through a median sternotomy, the distal part of the superior vena cava
      was anastomosed end-to-end to one side of the conduit. The other side of the
      graft was anastomosed end-to-side to the main pulmonary artery. The conduit was
      tailored to an appropriate length and anastomosed end-to-end to the inferior vena
      cava. The hemodynamic status of the animals was recorded before and after the
      establishment of the total cavopulmonary connection. RESULTS: Forty-five minutes
      after completion of total cavopulmonary connection, and for a total of 1 hour,
      hemodynamic measurements showed a decrease in mean arterial and mean pulmonary
      artery pressures, heart rate and cardiac output. The inferior vena caval pressure
      and total pulmonary vascular resistance were increased. CONCLUSIONS: A total
      cavopulmonary connection, performed on a beating heart, without extracorporeal
      circulation or other means of temporary bypass, although it is technically
      demanding, is feasible.<br />

PMID- 21169903
TI  - The effect of L-ascorbic acid and/or tocopherol supplementation on
      electrophysiological parameters of the colon of rats chronically exposed to lead.
AB  - BACKGROUND: The aim of this study was to assess the effect of diet
      supplementation with L-ascorbic acid (500 mg/L), tocopherol (3 mg/kg b.w.),
      and/or a water soluble analog of tocopherol (Trolox) (48 mg/L) on ion transport
      in the colon of rats subjected to a chronic exposure (9 months) to 0.1% lead
      acetate in drinking water. MATERIAL/METHODS: The electrophysiological parameters
      of the colon wall were measured with Ussing methods. Lead content in the whole
      blood was analyzed by graphite furnace atomic absorption spectrometry (GFAAS)
      using Zeeman correction. L-ascorbic acid and tocopherol in plasma was measured by
      high performance liquid chromatography. Immunohistochemical reaction was carried
      out for visualization of occludin, the intracellular tight junction protein.
      RESULTS: We showed a strong inhibitory effect of lead on the electrophysiological
      parameters, changes in intestinal permeability, disappearance of junctional
      occludin, decreased amount of mucus covering the colon surface, and the
      accumulation of PAS-positive substance in the apical region of the cytoplasm in
      the absorptive cells. CONCLUSIONS: Supplementation with tocopherol or Trolox did
      not exert a beneficial influence on the studied parameters. L-ascorbic acid
      positively influenced the examined electrophysiological parameters, as it
      cancelled the inhibitory influence of lead on ion transport in the rat colon. L
      ascorbic acid also protected against tight junction disruption of epithelial
      cells in the colon of the lead-treated rats. A similar effect was observed in the
      group of rats receiving lead and supplemented with L-ascorbic acid plus Trolox.

PMID- 21169904
TI  - The two layer method does not improve the preservation of porcine kidneys.
AB  - BACKGROUND: The Two layer method (TLM) has been extremely successful in the
      preservation of the pancreas. However, this has not been thoroughly investigated
      in other organs or in clinically relevant large animal models. The aim of this
      study was to assess the effects of TLM in a large animal model of kidney
      preservation. MATERIAL/METHODS: Porcine kidneys were retrieved after 10 minutes
      of warm ischaemic injury and flushed with 300 ml UW solution at 4 degrees C.
      Kidneys were then either placed in University of Wisconsin solution (UW) or TLM
      using pre-oxygenated perfluorodecalin and UW. Kidneys were stored for 18 hours at
      4 degrees C then reperfused with oxygenated autologous blood to assess renal
      function. RESULTS: Renal blood flow (RBF) was significantly lower and intra-renal
      resistance (IRR) higher in TLM compared to UW group [Area under the curve (AUC)
      RBF, UW; 427+/-168 vs TLM; 247+/-55 ml/min/100g.h; P=0.041, AUC IRR, UW; 7.7+/
      2.2 vs TLM; 10.5+/-1.9 ml/min/mmHg; P=0.041]. Levels of creatinine clearance
      (CrCl) were significantly lower in TLM group [AUC CrCl, UW; 1.8+/-1.0 vs TLM;
      0.6+/-0.4 ml/min/100 g.h; P=0.034]. Levels of lipid peroxidation were
      significantly lower in TLM group [8-isoprostane/Cr ratio 3h; UW 3338+/-896 vs TLM
      2072+/-886 pg/ml/mmol/L; P=0.04]. Levels of total nitric oxide were significantly
      higher in TLM group (P=0.009). CONCLUSIONS: TLM did not improve the preservation
      condition of porcine kidneys. Furthermore, there appeared to be increased
      inflammation, endothelial injury and reduced renal function compared to
      preservation with UW. Further experimental work is needed to determine the role
      of PFC in kidney preservation.

PMID- 21169905
TI  - The ability of the skin to absorb heat; the effect of repeated exposure and age.
AB  - BACKGROUND: When heat is applied to the skin, it is dissipated due to conductive
      heat flow in the tissue and the blood. While heat flow has been studied after
      applying a single heat exposure, the physiology of repeated exposures to local
      heat has not been well investigated. MATERIAL/METHODS: Twenty male and female
      subjects in the age range of 20-65 years old participated in a series of
      experiments during which a thermode was placed on their leg above the quadriceps
      muscle for 20 minutes, and on 3 sequential days, to see the effect of repeated
      local heat on skin blood flow, skin temperature, and on caloric transfer from a
      thermode used to raise skin temperature. RESULTS: The results of the experiment
      showed that, for young subjects, to raise skin temperature to 40 degrees C
      required more than double the calories required in older subjects. Further, in
      the younger subjects, the blood flow response in the first 20 minutes of heat
      exposure was over 30% higher than that seen in the older subjects. However, on
      the 2nd and 3rd day, the blood flow response of the younger subjects, was not
      significantly different between day 2 and 3, but was significantly less than day
      1. There was no statistical difference in the blood flow response between day 1,
      2 and 3 in the older subjects. In the younger subjects, in the 2 and 3rd day, the
      number of calories needed to warm the skin was also significantly less than that
      seen in the first day. CONCLUSIONS: In younger subjects but not older subjects,
      there appears to be some degree of acclimatization with an enhanced blood flow
      response in the first day that was protective to the skin which was not seen in
      repeated heat exposure.

PMID- 21169906
TI  - Post accessive social policy in the rehabilitation of adolescents following TBI.
AB  - BACKGROUND: The aim of this research was to evaluate the effectiveness of the
      post-accessive Conduct Disorder Therapy Program administered within the "Academy
      of Life" in the reduction of behavioural disorder in adolescents following
      traumatic brain injury (TBI). MATERIAL/METHODS: 100 adolescents from Gdansk and
      adjacent areas, psychiatrically diagnosed with "frontal lobe syndrome" following
      a TBI, were examined. Group A included 50 participants examined and treated at
      the Reintegration and Training Center of the Foundation for Persons with Brain
      Dysfunctions. Group B comprised 50 people matched for age and sex, under
      treatment at the Gdansk Center for Neuropsychological Studies, Gdansk-Poludnie
      Non-Public Health Care Center. Group A used the above therapy programme, while
      group B did not. The studies included an analysis of documentation, neuro-imaging
      (CT or MRI), clinical interviews, the Mini-Mental State Examination and the
      Frontal Behavioural Inventory. RESULTS: The therapy program had a significant
      impact on conduct disorders, the most visible differences being within
      neurological disorders and the least visible within cognitive disorders. It also
      influenced the social reintegration of adolescents following TBI, as demonstrated
      by the greater increase in the percentage of participants from group A returning
      to school and hobbies practised before the accident. CONCLUSIONS: The results
      indicate that the evaluated therapy program is effective in reducing behavioral
      disorders in adolescents following brain injury, and their reintegration into
      society.

PMID- 21169907
TI  - Elevated resistin opposed to adiponectin or angiogenin plasma levels as a strong,
      independent predictive factor for the occurrence of major adverse cardiac and
      cerebrovascular events in patients with stable multivessel coronary artery
      disease over 1-year follow-up.
AB  - BACKGROUND: Adipokines such as adiponectin and resistin, as well as angiogenin,
      may be associated with inflammation and atherosclerosis. The relationship between
      their levels and prognosis in high risk patients is, however, still unclear. The
      aim of this study was to evaluate the prognostic value of these adipokines in
      patients with stable multivessel coronary artery disease (MCAD).
      MATERIAL/METHODS: The study group comprised 107 MCAD patients (74% males, mean
      age 63 +/- 8 years). Adiponectin, resistin and angiogenin plasma levels were
      measured at admission and after 1-year follow-up. Primary end point (major
      adverse cardiac and cerebrovascular events--MACCE) was defined as cardiac death,
      nonfatal myocardial infarction, stroke, and hospitalization for angina or heart
      failure over a 1-year period. RESULTS: After 1-year follow-up, 9 (8%) patients
      died, all from cardiovascular causes. Primary end point was experienced by 32% of
      patients. Surgical treatment (CABG) was received by 51% of patients, while 49%
      were treated medically alone. Total cholesterol concentration levels >= 173 mg/dl
      were associated with a 7-fold increase (OR 7.3; 95% CI, 1.6-33.0); LDL >= 93.5
      mg/dl with a 16-fold increase (OR 16.3; 95% CI, 2.8-93.8), and resistin >= 17.265
      ng/ml with a 13-fold increase in MACCE risk (OR 13.5; 95% CI, 2.3-80.3). In
      multivariate analysis, a medical treatment strategy (p = 0.001), a higher CCS
      class (p = 0.004), resistin levels (p = 0.003) and a higher Gensini score (p =
      0.03) were independent predictors of MACCE. CONCLUSIONS: In stable patients with
      MCAD, elevated plasma resistin (as opposed to adiponectin or angiogenin) is a
      strong, independent predictive factor for the occurrence of MACCE over 1-year
      follow-up.

PMID- 21169908
TI  - The effect of physiotherapy on knee joint extensor and flexor muscle strength
      after anterior cruciate ligament reconstruction using hamstring tendon.
AB  - BACKGROUND: The aim of this paper is to present the physiotherapeutic program
      employed at the Rehabilitation Centre for the College of Physiotherapy in
      Wroclaw, Poland and its effectiveness by demonstrating the increase in strength
      of knee joint extensor and flexor muscles of patients after anterior cruciate
      ligament (ACL) reconstruction. MATERIAL/METHODS: Thirty-seven males participated
      in the physiotherapeutic program from the first week up to 8 months
      postoperatively. Each patient underwent an individual therapeutic program.
      Endoscopic reconstruction of a completely ruptured ACL was performed using
      Mitek's method (graft harvesting from flexor muscles). All patients previously
      underwent orthopedic and functional examinations, including measurements of the
      range of movement, knee and thigh circumference and strength of flexor and
      extensor muscles of the involved and uninvolved leg using a Biodex 3 System in
      both static and isokinetic modes. RESULTS: The outcome of the physiotherapeutic
      procedure, which is detailed in the paper, revealed a favorable effect of
      physiotherapy 6 months after ACL reconstruction. The observed 9% deficit in
      extensor muscle strength measured under isokinetic conditions of the involved
      knees compared with the uninvolved knees led us to conclude that the period of
      physiotherapy should be extended beyond 6 months for some patients. CONCLUSIONS:
      1. Six months of physiotherapy following ACL reconstruction in males favorably
      affected muscle strength values of the involved and uninvolved knees under static
      and isokinetic conditions. 2. The application of individual loads during the
      sixth month of physiotherapy resulted in similar values of extensor and flexor
      muscle strength measured under static conditions, and flexor muscle strength
      measured under isokinetic conditions in involved and uninvolved knees.

PMID- 21169909
TI  - Vestibular evoked myogenic potentials in patients with BPPV.
AB  - BACKGROUND: The probable cause of Benign Paroxysmal Positional Vertigo (BPPV) is
      a degeneration of the oto lithic organs (utricle and saccule). The aim of the
      study is to find possible alterations in Vestibular Evoked Myogenic Potentials
      (VEMP) recordings in BPPV patients, because the saccule is part of the VEMP
      pathway. MATERIAL/METHODS: 27 BPPV patients (24 unilateral and 3 bilateral) aged
      20 to 70 years and 30 healthy age matched controls. BPPV was diagnosed by the
      upbeating geotropic nystagmus found in the supine position with the head
      overextended towards one side. The subjects were investigated with pure tone
      audiometry, bi-thermal caloric test with electronystagmographic (ENG) recording,
      and VEMP recording. RESULTS: P1 latency and N1 latency did not present any
      statistical difference between control ears and affected ears of the BPPV
      population. The percentage of abnormal VEMP in the BPPV population was
      statistically higher than in the control ears (p < 0.005). No significant
      relationship could be shown between the occurrence of Canal Paresis and abnormal
      VEMP. No relationship was found between the side (right or left ear) where BPPV
      appeared clinically and the side where abnormal VEMP was registered. CONCLUSIONS:
      BPPV is a clinical entity associated with increased occurrence of abnormal VEMP
      recordings, possibly due to degeneration of the saccular macula, which is part of
      the neural VEMP pathway.

PMID- 21169910
TI  - Predictors of atrial fibrillation following coronary artery bypass surgery.
AB  - BACKGROUND: New-onset atrial fibrillation is the most common form of rhythm
      disturbance following coronary artery bypass grafting surgery (CABG). It is still
      unclear which factors have a significant impact on its occurrence after this
      procedure. The aim of this study was to evaluate clinical predictors of
      postoperative atrial fibrillation (POAF) after myocardial revascularization.
      MATERIAL/METHODS: We performed a retrospective analysis of 322 patients who
      underwent the first CABG operation without baseline atrial fibrillation. All
      subjects underwent laboratory blood tests, echocardiography and selective
      coronarography with ventriculography. Patients were continuously
      electrocardiographically monitored during the first 48-72 h after the operation
      for the occurrence of POAF. RESULTS: POAF was diagnosed in 72 (22.4%) of the
      patients. Multivariate logistic regression analysis was used to identify the
      following independent clinical predictors of POAF: age>=65 years (OR 1.78; 95%CI:
      1.06-2.76; p=0.043), hypertension (OR 1.97; 95%CI: 1.15-3.21; p=0.018), diabetes
      mellitus (OR 2.09; 95% CI: 1.31-5.33; p=0.010), obesity (OR 1.51; 95%CI: 1.03
      3.87; p=0.031), hypercholesterolemia (OR 2.17, 95%CI: 1.05-4.25; p=0.027),
      leukocytosis (OR 2.32, 95%CI: 1.45-5.24; p=0.037), and left ventricular segmental
      kinetic disturbances (OR 3.01; 95%CI: 1.65-4.61, p<0.001). CONCLUSIONS: This
      study demonstrates that advanced age, hypertension, diabetes, obesity,
      hypercholesterolemia, leukocytosis, and segmental kinetic disturbances of the
      left ventricle are powerful risk factors for the occurrence of POAF.

PMID- 21169911
TI  - Establishment of normal reference ranges for glycemic variability in Chinese
      subjects using continuous glucose monitoring.
AB  - BACKGROUND: Glycemic variability is increasingly recognized as an important issue
      in diabetes management. However, the lack of normative values may limit its
      applicability in the clinical setting. The objective of this study was to
      establish preliminary normal reference ranges for glycemic variability by
      analyzing continuous glucose monitoring (CGM) data obtained from healthy Chinese
      adults. MATERIAL/METHODS: Three-day CGM data were obtained from 434 healthy
      adults at 10 academic hospitals throughout China. Glycemic variability was
      calculated as the 24-hour mean amplitude of glycemic excursions (MAGE) and
      standard deviations (SD) of blood glucose readings. RESULTS: 434 healthy subjects
      (male 213, female 221; age 43 +/- 14, 20-69 years old; BMI 21.8 +/- 1.7 kg/m2,
      18.5-24.9 kg/m2) completed the study. MAGE and SD values for the 434 healthy
      subjects were 1.73 (1.08) mmol/L and 0.75 (0.42) mmol/L [median (interquartile
      range)], respectively. In both men and women, MAGE and SD tended to increase with
      age. Neither MAGE nor SD showed a significant difference between men and women.
      Values for both parameters were non-normally distributed within the population.
      The 95th percentiles of MAGE and SD were 3.86 and 1.40 mmol/L, respectively.
      These values were adopted as the upper limits of normal.< CONCLUSIONS: MAGE <3.9
      mmol/L and SD <1.4 mmol/L are recommended as the normal reference ranges for
      glycemic variability in Chinese adults. The values established in this study may
      facilitate the adoption of glycemic variability as a metric of overall glycemic
      control in diabetes.

PMID- 21169912
TI  - Large leg ulcers due to autoimmune diseases.
AB  - BACKGROUND: Large leg ulcers (LLU) may complicate autoimmune diseases. They pose
      a therapeutic challenge and are often resistant to treatment. To report three
      cases of autoimmune diseases complicated with LLU. CASE REPORT: Case 1. A 55-year
      old woman presented with long-standing painful LLU due to mixed connective tissue
      disease (MCTD). Biopsy from the ulcer edge showed small vessel vasculitis. IV
      methylprednisolone (MethP) 1 G/day, prednisolone (PR) 1mg/kg, monthly IV
      cyclophosphamide (CYC), cyclosporine (CyA) 100mg/day, IVIG 125G, ciprofloxacin+IV
      Iloprost+enoxaparin+aspirin (AAVAA), hyperbaric oxygen therapy (HO), maggot
      debridement and autologous skin transplantation were performed and the LLU
      healed. Case 2. A 45-year old women with MCTD developed multiple LLU's with non
      specific inflammation by biopsy. MethP, PR, hydroxychloroquine (HCQ),
      azathioprine (AZA), CYC, IVIG, AAVAA failed. Treatment for underlying the LLU
      tibial osteomyelitis and addition of CyA was followed by the LLU healing. Case 3.
      A 20-year-old man with history of polyarteritis nodosa (PAN) developed painful
      LLU's due to small vessel vasculitis (biopsy). MethP, PR 1 mg/kg, CYC, CyA 100
      mg/d, AAVAA failed. MRSA sepsis and relapse of systemic PAN developed. IV
      vancomycin, followed by ciprofloxacin, monthly IVIG (150 g/for 5 days) and
      infliximab (5 mg/kg) were instituted and the LLU's healed. CONCLUSIONS: LLU are
      extremely resistant to therapy. Combined use of multiple medications and services
      are needed for healing of LLU due to autoimmune diseases.

PMID- 21169913
TI  - Obesity control and low protein diet preserve or even improve renal functions in
      Bardet-Biedl syndrome: a report of two cases.
AB  - BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare autosomal-recessive disorder
      characterized by abdominal obesity, mental retardation, dysmorphic extremities,
      retinal dystrophy, hypogonadism, and kidney structural abnormalities or
      functional impairment. It is now considered a significant cause of chronic and
      end-stage renal disease in children. To the best of our knowledge there have been
      no previous studies on the role of diet in the management of renal functions in
      patients with BBS. CASE REPORTS: Two siblings, aged 32 and 27 years, with BBS are
      presented. On admission both patients were obese, with body mass indexes (BMI) of
      40 and 39 kg/m2. Their creatinine clearances (CrCl) were 41 and 24 mL/min. After
      2 years of follow-up with a diet consisting of 0.6 g/kg/day protein and 1400
      kcal/day energy, their BMI's were decreased to 29 and 27 kg/m2, whereas their
      CrCl's were increased to 44 and 32 mL/min, respectively. 99mTc-MAG3 scintigraphy
      also revealed improved renal function. CONCLUSIONS: Since this syndrome most
      likely results in end-stage renal disease, follow-up of renal dysfunction is
      essential. Low protein diet and/or obesity control may slow the progression of
      renal failure in patients with BBS.

PMID- 21169914
TI  - T tube drainage for spontaneous perforation of the extrahepatic bile duct.
AB  - BACKGROUND: Spontaneous perforation of the extrahepatic bile duct is very rare.
      We report a patient with a spontaneous perforation of the left hepatic bile duct
      who was diagnosed preoperatively. CASE REPORT: A 65-year-old woman was admitted
      to our hospital complaining of a right upper quadrant pain lasting for two days.
      She was diagnosed as having a perforated bile duct and peritonitis and underwent
      a laparotomy. After a cholecystectomy, T-tube drainage of the left hepatic duct
      was performed. The postoperative course was uneventful. The T tube was removed 25
      days after the surgery. CONCLUSIONS: A more noninvasive procedure, such as
      endoscopic treatment, should play a central role in the management of extra bile
      duct perforation. For this case, however, we chose to perform a laparotomy based
      on the patient's general condition and the presence of peritonitis. T tube
      decompression is effective and a safe and reliable method. The goal of treatment
      is to stop the bile leakage, resolve the choledocholithiasis and cholangitis, and
      reconstruct the bile duct.

PMID- 21169915
TI  - Aortic coarctation with Down syndrome.

PMID- 21169916
TI  - Hemodynamic efficacy of sequential hemoclip application using the Olympus HX
      110/610 reloadable clipping device in spurting bleedings.
AB  - BACKGROUND: Hemoclip application in GI-hemorrhage has proven to be effective.
      Clinical experience shows that multiple clips are frequently necessary. In 2005,
      an easily reloadable clip-applicator was introduced. We evaluated the hemodynamic
      efficacy of this new device. MATERIAL/METHODS: We prospectively compared the new
      clipping device (Olympus HX 110/610) in a validated experimental setting using
      the compactEASIE(r)-simulator for GI bleeding. The artificial blood circulation
      system in the simulator was connected to a pressure transducer. Four
      investigators of different endoscopic experience (1000-6000 endoscopies) treated
      12 bleeding sources each, with up to 6 clips for each bleeding location.
      Pressures were recorded to objectify the additive effects of sequential clip
      application on the reduction in vessel diameter. The intervention was abandoned
      if a maximum measurable pressure of 300 mmHg was achieved. RESULTS: Hemoclip
      application led to a significant increase of peak pressure (91+/-100 mmHg,
      p<0.001) and mean pressure (95+/-99 mmHg, p<0.001), representing a significant
      reduction in vessel diameter. Pooled data showed a significant stepwise increase
      in mean and maximum system pressure, resulting in reduction of vessel diameter up
      to the fifth hemoclip. On average, 5 clips (range 1-6) were used. More
      experienced endoscopists achieved a higher increase in mean pressure (167 and 118
      mmHg vs 72 and 23 mmHg, p<0.05). Mean reloading time was 39 seconds (19-49 sec).
      CONCLUSIONS: Sequential application of multiple hemoclips led to an increasing
      effect, comparable to the results of previous clinical trials. The number of
      hemoclips applied correlated inversely, but not significantly, with the
      endoscopist's experience. Expensive single-use clips appear dispensable in view
      of the short reloading time.

PMID- 21169917
TI  - Polymorphisms of the NRAMP1 gene: distribution and susceptibility to the
      development of pulmonary tuberculosis in the Greek population.
AB  - BACKGROUND: Ample evidence suggests that host genetic factors affect human
      susceptibility to tuberculosis. The natural resistance-associated macrophage
      protein 1 (NRAMP1) gene seems to play a role in the pathophysiology of a number
      of intracellular infections, including mycobacteria. A case-control study was
      conducted in the Greek population to determine whether NRAMP1 polymorphisms
      affect the susceptibility to development of overt pulmonary tuberculosis.
      MATERIAL/METHODS: NRAMP1 polymorphisms (3'UTR, D543N, INT4) were evaluated among
      142 patients with culture-positive pulmonary tuberculosis and 144 ethnically
      matched healthy controls having latent M. tuberculosis infection. Patients with
      human immunodeficiency virus infection were excluded. RESULTS: Out of the 3
      NRAMP1 polymorphisms, a trend of increased incidence of INT4 polymorphism was
      found in the patients' group compared to the control group. A lack of association
      was observed between the 2 groups as far as the other 2 polymorphisms (D543N,
      3'UTR) are concerned. INT4-CC homozygotes were found to have a higher risk to
      develop pulmonary tuberculosis compared to GG homozygotes (p=0.022). An increased
      incidence G/TGTG/C genotype combination was found in the patients' group as
      compared to controls. G/TGTG/C genotype combination was associated with a 36%
      higher risk of developing pulmonary tuberculosis (p=0.004) compared to the
      baseline expression of G/TGTG/G combination. CONCLUSIONS: INT4-NRAMP1
      polymorphism may have a role in the development of culture-positive pulmonary
      tuberculosis after an initial M. tuberculosis latent infection. The possible role
      of INT4-NRAMP1 polymorphism in the development of active pulmonary tuberculosis
      needs further investigation.

PMID- 21169918
TI  - Direct inhibitory effects of Ganciclovir on ICAM-1 expression and proliferation
      in human coronary vascular cells (SI/MPL-ratio: >1).
AB  - BACKGROUND: Treatment of the human cytomegalovirus (HCMV) infection with
      ganciclovir has beneficial indirect effects on the complex interactions of HCMV
      with restenosis, atherosclerosis, and transplant vascular sclerosis. The current
      study reports on direct effects of ganciclovir on expression of ICAM-1 and cell
      proliferation, key events of coronary atherosclerosis/restenosis. A potential
      clinical relevance of the data will be evaluated with the help of SI/MPL-ratio's.
      MATERIAL/METHODS: Definition of the SI/MPL-ratio: relation between significant
      inhibitory effects in vitro/ex vivo and the maximal plasma level after systemic
      administration in vivo (ganciclovir: 9 ug/ml). Part I of the study investigated
      in cytoflow studies the effect of ganciclovir (0.05-5000 ug/mL) on TNF-a induced
      expression of intercellular adhesion molecule 1 (ICAM-1) in endothelial cells
      derived from umbilical veins (HUVEC), human coronary endothelial cells (HCAEC),
      and human coronary smooth muscle cells (HCMSMC). Part II of the study analysed
      the effect of ganciclovir (0.05-5000 ug/mL) on cell proliferation (HUVEC, HCAEC,
      and HCMSMC). In part III cytotoxic effects of ganciclovir (0.05-5000 ug/mL) were
      studied (HUVEC, HCAEC, and HCMSMC). RESULTS: Ganciclovir caused slight but
      significant inhibitory effects on expression of ICAM-1 in HUVEC, HCAEC, and
      HCMSMC. In all three cell types studied strong dose depending significant
      antiproliferative effects of ganciclovir were detected. Partially, the
      antiproliferative effects of ganciclovir were caused by cytotoxic effects.
      CONCLUSIONS: SI/MPL-ratio's >1 in HCAEC and HCMSMC indicate that the inhibitory
      effects of gancliclovir on ICAM-1-expression and cell proliferation may only be
      expected in vivo following local high dose administration e.g. in drug eluting
      stents (DES).

PMID- 21169920
TI  - Evidence and its uses in health care and research: the role of critical thinking.
AB  - Obtaining and critically appraising evidence is clearly not enough to make better
      decisions in clinical care. The evidence should be linked to the clinician's
      expertise, the patient's individual circumstances (including values and
      preferences), and clinical context and settings. We propose critical thinking and
      decision-making as the tools for making that link. Critical thinking is also
      called for in medical research and medical writing, especially where pre-canned
      methodologies are not enough. It is also involved in our exchanges of ideas at
      floor rounds, grand rounds and case discussions; our communications with patients
      and lay stakeholders in health care; and our writing of research papers, grant
      applications and grant reviews. Critical thinking is a learned process which
      benefits from teaching and guided practice like any discipline in health
      sciences. Training in critical thinking should be a part or a pre-requisite of
      the medical curriculum.

PMID- 21169919
TI  - Intention, false beliefs, and delusional jealousy: insights into the right
      hemisphere from neurological patients and neuroimaging studies.
AB  - Jealousy sits high atop of a list comprised of the most human emotional
      experiences, although its nature, rationale, and origin are poorly understood. In
      the past decade, a series of neurological case reports and neuroimaging findings
      have been particularly helpful in piecing together jealousy's puzzle. In order to
      understand and quantify the neurological factors that might be important in
      jealousy, we reviewed the current literature in this specific field. We made an
      electronic search, and examined all literature with at least an English abstract,
      through Mars 2010. The search identified a total of 20 neurological patients, who
      experienced jealousy in relation with a neurological disorder; and 22 healthy
      individuals, who experienced jealousy under experimental neuroimaging settings.
      Most of the clinical cases of reported jealousy after a stroke had delusional
      type jealousy. Right hemispheric stroke was the most frequently reported
      neurological disorder in these patients, although there was a wide range of more
      diffuse neurological disorders that may be reported to be associated with
      different other types of jealousy. This is in line with recent neuroimaging data
      on false beliefs, moral judgments, and intention [mis]understanding. Together the
      present findings provide physicians and psychologists with a potential for high
      impact in understanding the neural mechanisms and treatment of jealousy. By
      combining findings from case reports and neuroimaging data, the present article
      allows for a novel and unique perspective, and explores new directions into the
      neurological jealous mind.

PMID- 21169921
TI  - How we empathize with others: a neurobiological perspective.
AB  - Empathy allows us to internally simulate the affective and cognitive mental
      states of others. Neurobiological studies suggest that empathy is a complex
      phenomenon, which can be described using a model that includes 2 modes of
      processing: bottom-up and top-down. Bottom-up neural processing is achieved via
      the mirroring representation systems that play a key role in the direct sharing
      of the emotional states of others. Top-down processing, known as cognitive
      perspective-taking or theory of mind, where the feelings of others are fully
      imagined and understood, is based on control and inhibition mechanisms. Available
      evidence indicates that empathic brain responses are likely to be influenced by
      several different modulating factors.

PMID- 21169922
TI  - The small peptide OGP(10-14) reduces proliferation and induces differentiation of
      TPO-primed M07-e cells through RhoA/TGFbeta1/SFK pathway.
AB  - BACKGROUND: Osteogenic growth peptide (OGP) is a 14-mer peptide found in relevant
      concentration in blood, and its carboxy-terminal fragment [OGP(10-14)] represents
      the active portion of the full-length peptide. In addition to stimulating bone
      formation, OGP(10-14) shows hematological activity. In fact, it highly enhances
      hematopoiesis-affecting stem progenitors. Moreover, OGP(10-14) reduces the growth
      and induces the differentiation of the hematological tumour cell line
      trombophoietin(TPO)-primed M07-e by interfering with RhoA and Src kinase
      pathways. In the present report, we went deeper into this mechanism and evaluated
      the possible interference of the OGP(10-14) signal pathway with TGFbeta1 and TPO
      receptor Mpl. MATERIAL/METHODS: In OGP(10-14)-treated M07-e cells cultured with
      or without RhoA and Src kinases inhibitors (C3 and PP2), expression of TGFbeta1,
      Mpl, and Src kinases was analyzed by immunoperoxidase technique. Activated RhoA
      expression was studied using the G-LISATM quantitative test. RESULTS: In M07-e
      cells, both OGP(10-14) and PP2 activate RhoA, inhibit Src kinases, reduce Mpl
      expression and increase TGFbeta1 expression. OGP(10-14) and PP2 show the same
      behavior, causing an additive effect when associated. CONCLUSIONS: OGP(10-14)
      induces TPO-primed M07-e cells differentiation through RhoA/TGFbeta1/SFKs
      signalling pathway. In particular OGP(10-14) acts as a Src inhibitor, showing the
      same effects of PP2.

PMID- 21169923
TI  - [Intraoperative injuries of bile ducts].
AB  - 125 patients with injuries of bile ducts were observed from 1988 to 2008 years.
      Minor injuries (ducts in the bed of the gall bladder) were registered in 64
      patients. Magistral bile ducts were injured in 61 cases. Analysis revealed 3 key
      points of the successful treatment of of such patients: type of the injury (cut,
      dissection, side wound), localization of the defect (intra- and extrahepatic
      ducts) and participation of a highly qualified surgeon.

PMID- 21169924
TI  - [Surgery for lung cancer in elderly].
AB  - The growth of malignant tumors of lungs among elderly patients together with
      overall increase of people older then 70, aroused new problems in surgery and
      anesthesiology. Nowadays, modern medicine succeeded minimal postoperative
      mortality and lethality among such patients, 19,7 and 6,4%, respectively. 3 and 5
      year survival among operated patients was 68 and 42%. Actually, overall lethality
      rate was determined mainly by relative and conquering diseases. Lobectomy should
      be considered a method of choice, although sublobar resection is appropriate by
      lung tumors of stages 1 and 2.

PMID- 21169925
TI  - [Spontaneous emphysema of the mediastinum].
AB  - Cases of 104 patients with the spontaneous emphysema of the mediastinum were
      thoroughly analyzed. The disease affects young men, aged less the 30 years, with
      asthma or chronic bronchitis. Differentiation should be made between iatrogenic
      esophageal or tracheobronchial rupture and spontaneous rupture of esophagus.
      Surgical treatment is indicated to less then 4% of patients with spontaneous
      mediastinal emphysema.

PMID- 21169926
TI  - [Diagnostics and surgical treatment of diaphragm ruptures].
AB  - 29 patients, aged 18-63 years, with diaphragm ruptures and severe polytraumatic
      injuries were treated. 26 patients had laparotomy, the rest 2 were thoracotomyzed
      for the surgical treatment. The rupture of the diaphragm was diagnosed during
      surgery in 8 (27,6%) patients, who were initially operated on cause of massive
      bleeding. In 16 (55,2%) cases there were no signs of bleeding, though patients
      showed clinical picture of abdominal contents' dislocation to the pleural cavity.
      Rupture of the diaphragm was misdiagnosed during the first operation and caused
      the second laparotomy in 4 (13,8%) patients. Rupture was left-sided in 28
      patients, right-sided in 1 case. Postoperative lethality was 13,8% (4 patients).

PMID- 21169927
TI  - [Septic complications of penetrating thoracic injuries].
AB  - 224 cases of septic complications after penetrating thoracic injuries were
      analyzed. Pleura empyem was observed in 105 of 7572 patients (overall number of
      the injured), lung abscess - in 22 cases, pericarditis was diagnosed in 108
      patients, costal and sternal osteomyelitis - in 26 and mediastinitis - in 21
      patients. Overall frequency of septic complication was 2,96%. Main reasons of
      septic complications were: massive blood loss, initial contamination, thoracotomy
      through the initially infected wound, long -lasting and coagulated hemothorax and
      late diagnosis and hospitalization. Staphylococcus aureus was the most frequent
      microbe detected - 29,4%. Lethality rate was 9,8% (22 patients). Adequate
      drainage of the wound allowed rehabilitation of the majority of patients. Cases
      with costal osteomyelitis required major surgical dissection in 73,1%.

PMID- 21169928
TI  - [Intraperitoneal ventral hernia plasty: the comparison of prosthetic materials].
AB  - Properties of abdominal wall intraperitoneal implants were assessed in vivo on 76
      rabbits. Implants of polytetrafluorethilene (PTFE), uncoated mesh polypropylene
      and polypropylene with one- and two-side collagen coat, oxycellulose and
      polyoxibutirate coated implants were compared. Animals were extracted from the
      experiment on 14, 90 and 210 days with further implant assessment. PTFE and
      collagen-coated prostheses showed the least number of adhesions. Retraction was 5
      14%. Prosthetic integration into the abdominal wall varied. PTFE and collagen
      coated polypropylene proved to be the most appropriate materials for
      intraperitonel mesh hernia plasty.

PMID- 21169929
TI  - [Etiology and pathogenesis of Mallory-Weiss syndrome].
AB  - Treatment results of 405 patients with Mallory-Weiss syndrome, X-ray gastric
      investigation in patients with severe bloating reflex were analyzed. Experimental
      part of the study involved rats and pigs, modeling esophageal and gastric
      rupture. Cardioesophageal and gastric cardial rupture happen in case of
      simultaneous sudden intragastric and intraabdominal hypertension, following the
      rule of Laplace.

PMID- 21169930
TI  - [Papilla Vateri restenoses after papillosphincterotomy].
AB  - Biliary tract was investigated in 105 patients after endoscopic
      papillosphincterotomy for choledocholithiasis and papillostenosis. The follow-up
      revealed papillary restenosis in 8,6%, which occurred during first 2 years after
      the procedure. Short cut of the duodenal papilla and intramural part of the
      common bile duct and anamnestic papillostenosis and septic cholangitis proved to
      be the main reasons of the papillary restenosis.

PMID- 21169931
TI  - [Evaluation of efficacy and safety of optimized based on the ketamine modified
      neuroleptanalgesia during operations on the biliary tract and liver].
AB  - A comparative analysis of efficacy and safety of the neuroleptanalgesia (NLA) and
      balanced general anesthesia during operations on the biliary tract and liver.
      Analysis of the results of comprehensive studies of hemodynamic, humoral
      homeostasis, liver function and clinical anesthesia showed that the optimized on
      the basis of ketamine modified NLA provides effective neurovegetative protection
      during operations on the organs of the hepatobiliary system, accompanied by
      obscure variations in the studied parameters. Traditional methods of the modified
      NLA is characterized by insufficient anesthesia, accompanied by pronounced
      physical inactivity circulation and a large number of "critical incidents".

PMID- 21169932
TI  - [Minimally invasive surgery for gall stones in elderly].

PMID- 21169933
TI  - [The use of plasma stream for the treatment of chronic osteomyelitis].
AB  - 80 patients with chronic osteomyelitis were treated. Plasma stream was used in
      complex treatment in 53,75%, which gave the notably less amount of unsatisfactory
      results of treatment, then in those patients, who were treated without the use of
      plasma stream. Therefore, authors declare, that a plasma stream allows the
      intensification of surgical treatment of osteomyelitis.

PMID- 21169934
TI  - [Brain cryodestruction in mammals in vivo].
AB  - 26 animals (13 pigs and 13 rabbits) were involved in the study. Liquid nitrogen
      cryodestruction experimental  machine was used. The following measurements and
      investigation were performed: invasive temperature measurement, intraoperative
      ultrasound, magnetic resonance imaging and pathomorphologic assessment. An ice
      sphere was hypoechogenic with hyperechogenic  contour by ultrasound. 
      Postoperative MRI showed signs of local ischemic oedema in cryodestruction zone,
      no signs of bleeding were detected. Morphologically zones of total necrosis,
      oedema and minor dystrophic changes were recognized. Cryodestruction proved to be
      a reliable technique of cold brain necrosis.

PMID- 21169935
TI  - [Intima-preserving exoprosthetics of ascending aortic aneurism: 15 years of
      experience].
AB  - Short- and long-term follow-up results of intima-preserving exoprosthetics of
      ascending aortic aneurism in 50 patients were studied. The group of control
      consisted of 54 patients, whom traditional linear prosthetics of ascending aortic
      aneurism had been performed. Time of artificial circulation and myocardial
      ischemia was significantly shorter in first group: 60,3+/-2,6 min and 21+/
      1,7min, respectively. Patients of both groups showed no significant aortic
      distension postoperatively (34,5+/-0,7 - 36,6+/-0,8 mm). Thus, a dosed resection
      of the ascending aortic aneurism with intima-preserving exoprosthetics proved to
      be relatively simple and promising technique.

PMID- 21169936
TI  - [Traumatic gunshot wounds of neck, thorax and abdomen].
AB  - Basing on the largest experience in the country, authors characterize the
      dynamics of growth, localizaton and severity of wounds from traumatic (nonlethal)
      weapon. Every third victim with neck wound had deep neck structures damage. Open
      wounds of thorax and abdomen, though performed from traumatic weapon, pose a
      certain life threat.

PMID- 21169937
TI  - [Radical thoracoplasty by the funneled thorax malformation in adults].
AB  - Early and long-term results of radical thoracoplasty in 114 adult patients with
      funnel chest are presented. The Sulamaa-Paltia operation was performed in 24
      patients, thoracoplasty with sternocostal complex fixing by arcuated nitinol
      plates was made in 30 patients. Thoracoplasty with sternocostal complex fixing by
      M-shaped nitinol plates was performed in 60 cases. Two patients after Sulamaa
      Paltia operation demonstrated the plate displacement, which caused the relapse of
      the disease. Those patients, who had other techniques applied, showed no signs of
      relapse. Thus, Sulamaa-Paltia operation allowed good results in 83,3% of the
      treated patients; the use of arcuated and M-shaped plates showed good results in
      93,3 and 98,3%, respectively.

PMID- 21169938
TI  - [Treatment of coagulation disoreders in patients with diabetes mellitus type II].
AB  - Efficacy of out-hospital treatment of coagulation disorders in patients with
      diabetes mellitus type II (DMII) in comparison with non-diabetic patients after
      aortic-femoral reconstruction was studied. Long-term results were obtained within
      65,1+/-3,95 months after surgery. Data of 67 patients were obtained, of them 32
      had severe DMII, 35 patients had no diabetic disorders. 94% of patients had
      various hypercoagulation disorders and thrombophilia stage I-II. Desagregant
      therapy was noneffective in 70,1% of patients. Patients with atherosclerosis
      after reconstructive vascular surgery showed disorders of both thrombocytic and
      plasma links of coagulation, which requires combined (anticoagulant and
      desagregant) therapy. Patients with DMII require also blood glucose and HbA1c
      control postoperatively.

PMID- 21169939
TI  - [Non-ulcer gastrointestinal bleedings].
AB  - Diagnostic and treatment protocol of non-ulcer gastrointestinal bleedings is
      defined. Special attention is paid to rare reasons of gastrointestinal bleedings,
      such as false aneurisms of the celiac trunk vessels. Applying diagnostic protocol
      and using endovascular techniques provide a dramatic improvement is treatment of
      such patients.

PMID- 21169940
TI  - [Pathogenesis of enteral insufficiency in patients with postoperative
      peritonitis].
AB  - Enteral insufficiency is considered to trigger the syndrome of endogenous
      intoxication and, further, multiple organ failure. Enteral insufficiency often
      accompanies postoperative septic complications, such as peritonitis. Morphologic
      changes of the intestinal wall by septic peritonitis consisted of edema,
      fibrinous degradation of muscular layer and dystrophy of local nervous pathways.
      Microbiologic analysis of intestinal and gastric contents, peritoneal fluid and
      blood samples demonstrated a broad spectrum of pathogenic flora. Besides,
      enterotoxin allocated from blood and intestinal contents coincided in all cases.
      Adequate algorithm of detoxication, including extracorporal methods, had been
      worked out.

PMID- 21169941
TI  - [Plasty of extrahepatic biliary ducts with the use of ileal autotransplantate].
AB  - A method of extrahepatic biliary duct plasty with the use of tubular ileal
      autotransplantate of 1 sm in diameter was presented in 19 patients with benign
      strictures. The transplantate on the vascular pedicle was created by resection of
      the antimesenterial side of the intestinal loop. Distally the anastomosis was
      performed with the common bile duct, including, thus, papilla Vateri into the
      bile passage (4 patients). By the impossibility of the latter, the anastomosis
      was performed with the vertical part of duodenum (16 patients). Postoperative
      follow-up variated from 1 to 15 years. 18 patients demonstrated good long-term
      result, 1 patients had a stricture recurrence.

PMID- 21169942
TI  - [Surgical treatment of chronic colostasis in patients with dolichocolon].
AB  - Method of the combined surgical treatment of patients with coloproctogenic
      constipation and dolichocolon and internal rectal prolapse had been worked out.
      The use of the suggested technique effectively prevents anorectal obstruction
      relapse.

PMID- 21169943
TI  - Time heals everything.

PMID- 21169944
TI  - Needless waste.

PMID- 21169945
TI  - Infant oral mutilation.

PMID- 21169946
TI  - Specialist fees.

PMID- 21169947
TI  - An elegant solution.

PMID- 21169948
TI  - It is reprehensible.

PMID- 21169950
TI  - Local dental committees back BDA red tape campaign.

PMID- 21169962
TI  - Commentary on: Perceptions of first year foundation dentists on oral health
      education and its role in general dental practice.

PMID- 21169952
TI  - Easy to swallow cookbook commended during mouth cancer awareness week.

PMID- 21169963
TI  - Commentary on: Disinfection of dental impressions - compliance to accepted
      standards.

PMID- 21169964
TI  - Perceptions of first year foundation dentists on oral health education and its
      role in general dental practice.
AB  - To explore the perceptions of first year foundation dentists (FD1s) regarding
      oral health education (OHE) and its role in general dental practice. DESIGN:
      Focus group discussions. SETTING: Postgraduate training venues and general dental
      practices utilised for foundation training in South Wales, UK. SUBJECTS
      (MATERIALS) AND METHODS: Nineteen FD1s accepted an invitation to take part in a
      series of focus groups. Focus groups were transcribed and data analysed using a
      constructive process of thematic content analysis to identify themes and theories
      relating to the FD1s' understanding of OHE and its role in the delivery of care
      as general dental practitioners. RESULTS: The data fell into three broad
      categories: the teaching of OHE delivery at undergraduate level; factors
      influencing the 'frequency and content' of OHE delivery; and barriers to
      'effective and successful' OHE. The first category identified perceptions of the
      'gold standard' of OHE following undergraduate experiences. The practicalities of
      the acquisition of technical skills had created a simplistic compartmentalised
      view of OHE which was not a priority in adult dental care. The second category
      covered triggers for delivering OHE; in general these were reactive rather than
      preventive. The last category dealt with successful OHE; unsuccessful OHE was
      attributed to the patient although communication barriers were recognised.
      CONCLUSION: The subtle but important difference between OHE and oral health
      promotion (OHP) in terms of its role in general dental practice is recognised
      theoretically but not as a reality in practice. OHE is often compartmentalised
      and a simplistic approach to its delivery is taken. Against a backdrop of
      commissioning to improve health this has implications in developing
      organisational processes within general dental practice and training in order to
      achieve this.

PMID- 21169966
TI  - Disinfection of dental impressions - compliance to accepted standards.
AB  - INTRODUCTION: The responsibility of ensuring impressions have been cleaned and
      disinfected before dispatch to the dental laboratory lies solely with the
      dentist. Uncertainty of impression disinfection risks both the health of the
      receiving dental technician and potential repeat disinfection of an already
      disinfected impression with detrimental consequences for its dimensions.
      OBJECTIVE: To ascertain, from the perspectives of dentists and dental
      technicians, current impression decontamination and disinfection practices with,
      in the case of the technicians, an estimate of the relative prevalence of
      contaminated voids within apparently disinfected impressions. DESIGN: Anonymous
      postal questionnaire. METHOD: Dentist (n = 200) and dental technician (n = 200)
      potential participants, selected at random from the registers held by the General
      Dental Council, were invited to complete an anonymous postal questionnaire that
      sought to establish current practices and perceived effectiveness of impression
      disinfection. RESULTS: Questionnaire return rates of 42.1% and 31.2% were
      recorded for dentists and dental technicians respectively. A wide range of
      solutions, at different dilutions of the same product, was used by the dentists
      to disinfect dental impressions. 37.2% rinsed the impressions with water, and
      2.6% always brushed debris away, before disinfection. 24.7% of dentists did not
      inform the laboratory of disinfection. Irrespective of the disinfection status of
      the received impressions, 50% of the responding dental technicians disinfected
      all impressions. 95% of them had received blood-contaminated impressions. 15% had
      encountered blood-filled voids upon trimming back the peripheries of impressions.
      64.7% were confident that the impressions received by them had been disinfected
      by the dentists. CONCLUSIONS: Compliance with good practice is less than ideal
      and education in impression disinfection for both dentists and dental technicians
      is required to address this.

PMID- 21169989
TI  - Chromatin condensation via the condensin II complex is required for peripheral T
      cell quiescence.
AB  - Naive T cells encountering their cognate antigen become activated and acquire the
      ability to proliferate in response to cytokines. Stat5 is an essential component
      in this response. We demonstrate that Stat5 cannot access DNA in naive T cells
      and acquires this ability only after T-cell receptor (TCR) engagement. The
      transition is not associated with changes in DNA methylation or global histone
      modification but rather chromatin decondensation. Condensation occurs during
      thymocyte development and proper condensation is dependent on kleisin-beta of the
      condensin II complex. Our findings suggest that this unique chromatin
      condensation, which can affect interpretations of chromatin accessibility assays,
      is required for proper T-cell development and maintenance of the quiescent state.
      This mechanism ensures that cytokine driven proliferation can only occur in the
      context of TCR stimulation.

PMID- 21169990
TI  - Atg1-mediated myosin II activation regulates autophagosome formation during
      starvation-induced autophagy.
AB  - Autophagy is a membrane-mediated degradation process of macromolecule recycling.
      Although the formation of double-membrane degradation vesicles (autophagosomes)
      is known to have a central role in autophagy, the mechanism underlying this
      process remains elusive. The serine/threonine kinase Atg1 has a key role in the
      induction of autophagy. In this study, we show that overexpression of Drosophila
      Atg1 promotes the phosphorylation-dependent activation of the actin-associated
      motor protein myosin II. A novel myosin light chain kinase (MLCK)-like protein,
      Spaghetti-squash activator (Sqa), was identified as a link between Atg1 and
      actomyosin activation. Sqa interacts with Atg1 through its kinase domain and is a
      substrate of Atg1. Significantly, myosin II inhibition or depletion of Sqa
      compromised the formation of autophagosomes under starvation conditions. In
      mammalian cells, we found that the Sqa mammalian homologue zipper-interacting
      protein kinase (ZIPK) and myosin II had a critical role in the regulation of
      starvation-induced autophagy and mammalian Atg9 (mAtg9) trafficking when cells
      were deprived of nutrients. Our findings provide evidence of a link between Atg1
      and the control of Atg9-mediated autophagosome formation through the myosin II
      motor protein.

PMID- 21169991
TI  - A quantitative RNA code for mRNA target selection by the germline fate
      determinant GLD-1.
AB  - RNA-binding proteins (RBPs) are critical regulators of gene expression. To
      understand and predict the outcome of RBP-mediated regulation a comprehensive
      analysis of their interaction with RNA is necessary. The signal transduction and
      activation of RNA (STAR) family of RBPs includes developmental regulators and
      tumour suppressors such as Caenorhabditis elegans GLD-1, which is a key regulator
      of germ cell development. To obtain a comprehensive picture of GLD-1 interactions
      with the transcriptome, we identified GLD-1-associated mRNAs by RNA
      immunoprecipitation followed by microarray detection. Based on the computational
      analysis of these mRNAs we generated a predictive model, where GLD-1 association
      with mRNA is determined by the strength and number of 7-mer GLD-1-binding motifs
      (GBMs) within UTRs. We verified this quantitative model both in vitro, by
      competition GLD-1/GBM-binding experiments to determine relative affinity, and in
      vivo, by 'transplantation' experiments, where 'weak' and 'strong' GBMs imposed
      translational repression of increasing strength on a non-target mRNA. This study
      demonstrates that transcriptome-wide identification of RBP mRNA targets combined
      with quantitative computational analysis can generate highly predictive models of
      post-transcriptional regulatory networks.

PMID- 21169992
TI  - Specificity of IRF4 translocations for primary cutaneous anaplastic large cell
      lymphoma: a multicenter study of 204 skin biopsies.
AB  - Current pathologic criteria cannot reliably distinguish cutaneous anaplastic
      large cell lymphoma from other CD30-positive T-cell lymphoproliferative disorders
      (lymphomatoid papulosis, systemic anaplastic large cell lymphoma with skin
      involvement, and transformed mycosis fungoides). We previously reported IRF4
      (interferon regulatory factor-4) translocations in cutaneous anaplastic large
      cell lymphomas. Here, we investigated the clinical utility of detecting IRF4
      translocations in skin biopsies. We performed fluorescence in situ hybridization
      (FISH) for IRF4 in 204 biopsies involved by T-cell lymphoproliferative disorders
      from 182 patients at three institutions. In all, 9 of 45 (20%) cutaneous
      anaplastic large cell lymphomas and 1 of 32 (3%) cases of lymphomatoid papulosis
      with informative results demonstrated an IRF4 translocation. Remaining
      informative cases were negative for a translocation (7 systemic anaplastic large
      cell lymphomas; 44 cases of mycosis fungoides/Sezary syndrome (13 transformed);
      24 peripheral T-cell lymphomas, not otherwise specified; 12 CD4-positive
      small/medium-sized pleomorphic T-cell lymphomas; 5 extranodal NK/T-cell
      lymphomas, nasal type; 4 gamma-delta T-cell lymphomas; and 5 other uncommon T
      cell lymphoproliferative disorders). Among all cutaneous T-cell
      lymphoproliferative disorders, FISH for IRF4 had a specificity and positive
      predictive value for cutaneous anaplastic large cell lymphoma of 99 and 90%,
      respectively (P=0.00002, Fisher's exact test). Among anaplastic large cell
      lymphomas, lymphomatoid papulosis, and transformed mycosis fungoides, specificity
      and positive predictive value were 98 and 90%, respectively (P=0.005). FISH
      abnormalities other than translocations and IRF4 protein expression were seen in
      13 and 65% of cases, respectively, but were nonspecific with regard to T-cell
      lymphoproliferative disorder subtype. Our findings support the clinical utility
      of FISH for IRF4 in the differential diagnosis of T-cell lymphoproliferative
      disorders in skin biopsies, with detection of a translocation favoring cutaneous
      anaplastic large cell lymphoma. Like all FISH studies, IRF4 testing must be
      interpreted in the context of morphology, phenotype, and clinical features.

PMID- 21169993
TI  - Eosinophilic gastritis: histopathological characterization and quantification of
      the normal gastric eosinophil content.
AB  - There is limited information about normal eosinophil counts in the gastric
      mucosa. The purpose of this study was to evaluate the histopathology of 60
      patients whose biopsies showed increased eosinophils in the gastric mucosa. We
      also investigated the eosinophil content in gastric biopsies from normal controls
      (matched for age, sex, and zip code), from patients with Helicobacter pylori
      gastritis, and patients with Crohn's disease. Eosinophils were counted in five
      random high-power fields (HPFs) and reported in eosinophils/mm(2). Involvement of
      the muscularis mucosae or submucosa, sheets of eosinophils, and infiltration of
      the gastric epithelium were also evaluated. The median eosinophil count in the
      study patients was 539 eosinophils/mm(2); mean+/-SD=653+/-418 eosinophils/mm(2);
      range 127-2108. Sheets of eosinophils were seen in 38 patients, 27 showed
      involvement of the muscularis mucosae or submucosa. There were 7 patients without
      epithelial infiltration by eosinophils, whereas 34 were tallied as rare and 19
      were scored as abundant. No study patient had no evidence of H. pylori. The mean
      eosinophil count for the 135 normal controls was 15.5+/-16.8 SD eosinophils/mm(2)
      (range 0-110); in the 93 controls with H. pylori gastritis the mean eosinophil
      count was 25+/-32.6 SD eosinophils/mm(2) (range 0-219); and for the 53 controls
      with Crohn's disease it was 31.4+/-44.4 SD eosinophils/mm(2) (range 0-203). There
      were no significant differences between the counts in biopsies from the antrum
      and corpus, and no significant variations by age, geographic location, or season.
      This study confirms that, in the United States population, the normal gastric
      eosinophilic counts are usually <38 eosinophils/mm(2). We recommend 'histological
      eosinophilic gastritis' for the diagnosis of gastric biopsies that show an
      average density >=127 eosinophils/mm(2) (or >=30 eosinophils per HPF) in at least
      five HPFs in the absence of known associated causes of eosinophilia.

PMID- 21169994
TI  - Funding the future in UK science.
AB  - Against a backdrop of some of the most savage spending cuts in the developed
      world, the UK science budget has emerged relatively unscathed, but funding
      priorities may yet prove problematic.

PMID- 21169995
TI  - Control of T cell activation by vitamin D.

PMID- 21169997
TI  - Diet, gut microbiota and immune responses.
AB  - The fields of immunology, microbiology, nutrition and metabolism are rapidly
      converging. Here we expand on a diet-microbiota model as the basis for the
      greater incidence of asthma and autoimmunity in developed countries.

PMID- 21169998
TI  - ZAPS electrifies RIG-I signaling.

PMID- 21169999
TI  - Fine tuning NF-kappaB: new openings for PKC-zeta.

PMID- 21170000
TI  - Cooperative regulatory events and Foxp3 expression.

PMID- 21170001
TI  - Explaining discordant coordination.

PMID- 21170003
TI  - Antiplatelet therapy: Clopidogrel-PPI interaction, an ongoing controversy.

PMID- 21170004
TI  - Seek don't screen for oral cancer.

PMID- 21170005
TI  - Excerpts from an interview with Debora Matthews.

PMID- 21170006
TI  - Clinical recommendations for oral cancer screening.
AB  - SCOPE AND PURPOSE: To address the benefits and limitations of oral cancer
      screening and the use of adjunctive screening aids to visualise and detect
      potentially malignant and malignant oral lesions. Squamous cell carcinomas of the
      lips and cancers of the oropharynx (including the posterior one-third of the base
      of the tongue and the tonsils were excluded. METHODOLOGY: A specially convened
      expert panel evaluated the available evidence which was derived from a systematic
      search of Medline and the Cochrane Library. Further details about the search are
      available in a supplement to the published article available on the Journal of
      the America Dental Association's website
      (http://jada.ada.org/cgi/content/full/141/5/509). Qualitative synthesis of the
      data was performed by the panel. Where consensus could not be reached majority
      voting was employed. Recommendations were reviewed by internal and external
      scientific experts and organisations. After review recommendations were revised
      where appropriate and the ADA Council on Scientific Affairs approved the final
      clinical recommendations. REVIEW AND UPDATING: No information provided in
      article. RECOMMENDATIONS: The key recommendations were all classified as level D
      being based on grade IV evidence or extrapolated from grade I, II or III evidence
      using a system based on Shekelle et al.(1) The main recommendations can be
      summarised as:1) Clinicians should remain alert for signs of potentially
      malignant lesions or early-stage cancers in all patients while performing routine
      visual and tactile examinations, particularly for patients who use tobacco or who
      are heavy consumers of alcohol. 2) For seemingly innocuous lesions, clinicians
      should follow up in seven to 14 days to confirm persistence after removing any
      possible cause to reduce the potential for false-positive screening results. 3)
      For lesions that raise suspicion of cancer or for lesions that persist after
      removal of a possible cause, clinicians should communicate the potential benefits
      and risks of early diagnosis. Considerations include the following: a) that even
      suspicious lesions identified during the course of a routine visual and tactile
      examination may represent false positives; b) that clinical confirmation (a
      second opinion) can be sought from a dental or medical care provider with
      advanced training and experience in diagnosis of oral mucosal disease so as to
      reduce the potential for a false positive or false negative oral cancer screening
      result; c) that a malignancy or non-malignancy can be confirmed only via
      microscopic examination that requires a surgical biopsy; d) that a decision to
      pursue a biopsy to confirm the presence or absence of malignancy should be made
      in the context of informed consent. 4) Although transepithelial cytology has
      validity in identifying disaggregated dysplastic cells, the panel suggests
      surgical biopsy for definitive diagnosis. RESEARCH RECOMMENDATIONS: In all, 15
      separate research recommendations were made ranging from determining the
      prevalence of potentially malignant oral mucosal lesions in the United States to
      whether the use of adjunctive devices improves patient education and adherence to
      follow-up care.

PMID- 21170007
TI  - Oral cancer screening programmes.
AB  - DATA SOURCES: The Cochrane Oral Health Group Trials Register, the Cochrane
      Central Register of Controlled Trials (CENTRAL), Medline, Embase and CANCERLIT.
      STUDY SELECTION: Randomised controlled trials (RCTs) of screening for oral cancer
      or potentially malignant disorders using visual examination, toluidine blue,
      fluorescence imaging or brush biopsy were included. There were no restrictions
      regarding language or date of publication. DATA EXTRACTION AND SYNTHESIS: The
      original review identified 1,389 citations and this update identified an
      additional 330 studies. Validity assessment, data extraction and statistics
      evaluation were undertaken by six independent review authors. RESULTS: Only one 9
      year cluster RCT was included (n = 13 clusters: 191,873 participants). No
      statistically significant differences in the age-standardised oral cancer
      mortality rates for the screened group (16.4/100,000 person-years) and the
      control group (20.7/100,000 person-years) were identified. A 43% reduction in
      mortality was reported between the intervention cohort (29.9/100,000 person
      years) and the control arm (45.4/100,000) for high-risk individuals who used
      tobacco or alcohol or both, which was statistically significant. However, this
      study had a number of methodological weaknesses and the associated risk of bias
      was high. CONCLUSIONS: Although there is evidence that a visual examination as
      part of a population-based screening programme reduced the mortality rate of oral
      cancer in high-risk individuals, whilst producing a stage shift and improvement
      in survival rates across the population as a whole, the evidence is limited to
      one study and is associated with a high risk of bias. This was compounded by the
      fact that the effect of cluster randomisation was not accounted for in the
      analysis. Furthermore, no robust evidence was identified to support the use of
      other adjunctive technologies like toluidine blue, brush biopsy or fluorescence
      imaging within a primary care environment. Further RCTs are recommended to assess
      the efficacy, effectiveness and cost-effectiveness of a visual examination as
      part of a population based screening programme.

PMID- 21170008
TI  - Does toluidine blue detect more oral cancer?
AB  - DESIGN: A randomised controlled trial. INTERVENTION: 28,167 individuals aged 15
      years or older who were invited participate in a screening programme, 17,890 who
      lacked oral habits such as cigarette smoking or chewing betel quid were excluded
      leaving 10,277 eligible individuals. Of these, 2,302 refused to participate
      leaving a sample of 7,975 for randomisation. The test group gargled with
      toluidine blue solution while the control group was given a placebo dye of the
      same colour. Each participant was visually examined by one of six dentists with
      additional training. The presence of any visible lesion in the oral cavity (e.g.
      abnormal mucosal lesions related to OPMLs and other suspected lesions such as
      lichen planus, oral ulcer, hyperkeratosis, candidiasis, etc) was recorded as
      screen-positive. The screen-positive participants to a specialist were referred
      to a specialist for a definite clinical diagnosis within 10 to 14 days, to reduce
      false-positivity, and biopsies were arranged if oral lesions were present. The
      occurrence of oral cancer, survival status, and causes of death of the studied
      participants for the entire cohort was obtained from the National Cancer Registry
      and the National Household Registry until the end of 2004. OUTCOME MEASURE: The
      number of oral lesions, premalignant or not. RESULTS: In the test group 389
      (9.5%) individuals had a positive screen compared with 322 (8.3%) in the control
      group. Two oral cancers were identified out of those with a positive screen
      presenting (n=320) for the referral examination from the test group with three
      oral cancers out of the 293 in those who complied in the control group. There
      were three oral cancers ascertained by the end of the follow-up among the screen
      negatives in each arm (test and control) by the end of the followup period. The
      numbers of OPMLs in each arm of the study are shown in Table 1. CONCLUSIONS: We
      demonstrated that using toluidine blue as an adjunctive tool for visual screening
      can detect significantly more oral submucous fibrosis and slightly more
      leukoplakia among high-risk individuals with habits of cigarette smoking or betel
      quid chewing as compared with visual screening alone.

PMID- 21170009
TI  - Public awareness of oral cancer and associated risk factors is low.
AB  - STUDY DESIGN: A survey was carried out over a three-year period (2004-2007) in
      Maggie's Cancer Caring Centres or in patients' homes in Glasgow and Edinburgh,
      Scotland. Participants included young patients diagnosed with oral cancer. DATA
      COLLECTION AND ANALYSIS: Data were collected by interview using a semi-structured
      interview schedule. The interview transcripts were analysed using a thematic
      framework and with the aid of NVivo qualitative analysis software (Version 8).
      RESULTS: The majority of the cohort knew that smoking and alcohol could cause
      oral cancer. None thought it would happen to them, however. Descriptions of
      symptoms varied widely and several participants used self-treatment modalities
      provided from a pharmacy. There were various causes of patient delay, and self
      treatment was not the only cause. Reinterpretation of symptoms without seeking
      professional help was not uncommon. None of the patients suspected that they had
      oral cancer until it was confirmed by their general practitioner (GP) or general
      dental practitioner (GDP). CONCLUSIONS: The study confirms gaps in understanding
      and awareness of oral cancer. Most survey participants had heard of oral cancer.
      However, they did not think their symptoms were indicative of cancer and they
      self-managed the problem. The culture of not bothering the GP/GDP unless the
      condition was perceived as serious is a barrier to early diagnosis and treatment.
      Findings support that further public awareness of oral cancer and its symptoms is
      required to alert the public that if their symptoms persist beyond three weeks,
      they need a professional opinion.

PMID- 21170010
TI  - Effectiveness of chlorhexidine varnish for preventing caries uncertain.
AB  - DATA SOURCES: Medline, Embase, the Cochrane Central Register of Controlled Trials
      (CENTRAL), and reference lists of reviews. STUDY SELECTION: Randomised or quasi
      randomised controlled trials with blind outcome assessment and a minimum duration
      of 1 year comparing chlorhexidine varnish to placebo, no treatment or fluoride
      varnish were included. Split-mouth trials were included but analysed separately.
      The primary outcome measure was the caries increment determined using the decayed
      missing and filled surface (DMFS/dmfs) index. Only trials where caries were
      assessed by visual/visual-tactile or radiographic methods were included. DATA
      EXTRACTION AND SYNTHESIS: Data were extracted by one author and verified by a
      second. It was planned to present the results graphically in a forest plot and
      formally assess statistical heterogeneity. However, due to missing data and
      variation in the reporting of outcomes, this was not possible. Consequently a
      narrative summary of the results is presented with parallel-group and split-mouth
      trials considered separately. Heterogeneity was assessed informally. RESULTS: 12
      trials were included (eight parallel group, four split-mouth trials) There was
      considerable variation between trials in the concentration and frequency of
      application of the chlorhexidine varnish, in baseline caries levels and in
      background exposure to fluoride. Six parallel group trials reported no
      statistically significant difference in caries increment in permanent teeth with
      the application of chlorhexidine varnish compared to placebo or no treatment. The
      results of 4 split-mouth trials were conflicting: 2 trials found no significant
      difference in caries increment and 2 reported statistically significant results
      in favour of chlorhexidine varnish. One trial of the effect of chlorhexidine
      varnish in primary teeth demonstrated a statistically significant reduction in
      caries increment. The results of 1 trial comparing chlorhexidine varnish with
      fluoride varnish for preventing caries in adolescents were equivocal.
      CONCLUSIONS: Evidence regarding the effectiveness of chlorhexidine varnish for
      preventing caries is inconclusive. Further well-conducted randomised trials are
      required before chlorhexidine varnish can be recommended for caries prevention.

PMID- 21170011
TI  - Xylitol gum, plaque pH and mutans streptococci.
AB  - DESIGN: This was a randomised clinical trial (note that the initial screening
      used a cluster randomised in part design). INTERVENTION: A total of 176 children
      (7-9 years old) with high MS scores were randomised into equal groups. For 6
      months the xylitol group chewed five times during the day, 11.6 grams of a mixed
      gum containing 36.6% xylitol and other polyols (34.5%). while the control group
      chewed an identical dose of a non xylitol gum sweetened with a mixture of
      different polyols (71.1%). OUTCOME MEASURE: At baseline, 3 months, 6 months and 9
      months (3 months after chewing) children were assessed for both plaque
      acidogenicity (after sucrose challenge) and salivary MS. RESULTS: Statistically
      significant differences were found between both groups at 3, 6 and 9 months, in
      'area under the curve' (AUC) graphs, with lower plaque pH values in the xylitol
      group at 3 and 6 months and decreasing difference at 9 months. There was no
      significant difference between the maximum pH fall in both groups, and only small
      differences in minimum pH values at 3 and 6 months. There was significantly lower
      MS level in the xylitol compared with the control group. In addition there was a
      significant relationship between changes in MS levels, and changes in AUC.
      CONCLUSIONS: This randomised clinical trial suggests that the use of high-dose
      xylitol chewing gum has beneficial effects on plaque pH and MS in children at
      high risk of caries.

PMID- 21170012
TI  - Defective amalgams - repair or replace?
AB  - DATA SOURCES: Cochrane Oral Health Group Trials Register, the Cochrane Central
      Register of Controlled Trials (CENTRAL), Medline, Embase, ISI Web of Science, ISI
      Web of Science Conference Proceedings, BIOSIS, OpenSIGLE. Reference lists of all
      eligible trials and review articles, and their reference lists were searched.
      STUDY SELECTION: Trials were selected if they met the following criteria:
      randomised or quasi-randomised controlled trial, involving replacement and repair
      of amalgam restorations. DATA EXTRACTION AND SYNTHESIS: Titles and abstracts were
      assessed independently by two authors. Full papers were obtained for relevant
      articles. Data synthesis was to follow Cochrane Collaboration statistical
      guidelines. RESULTS: 145 potentially eligible studies were identified. Only three
      studies were analysed further but none of these met the inclusion criteria and
      all were excluded from this review. CONCLUSIONS: There are no published
      randomised controlled clinical trials (RCTs) relevant to this review question.
      There is a need for methodologically sound RCTs reported according to the
      Consolidated Standards of Reporting Trials (CONSORT) statement (www.consort
      statement.org/). Further research needs to explore qualitatively the views of
      patients on repairing versus replacement and investigate themes around pain,
      distress and anxiety, time and costs.

PMID- 21170013
TI  - Defective resin composite - repair or replace?
AB  - DATA SOURCES: Cochrane Oral Health Group Trials Register, the Cochrane Central
      Register of Controlled Trials (CENTRAL), Medline, Embase, ISI Web of Science, ISI
      Web of Science Conference Proceedings, BIOSIS, OpenSIGLE. Reference lists of all
      eligible trials and review articles and their reference lists were searched.
      STUDY SELECTION: Trials were selected if they met the following criteria:
      randomised or quasi-randomised controlled trial, involving replacement and repair
      of resin composite restorations. DATA EXTRACTION AND SYNTHESIS: Titles and
      abstracts were assessed independently by two review authors for relevance . Full
      papers were obtained for relevant articles and both review authors studied these.
      Data synthesis was to follow Cochrane Collaboration statistical guidelines.
      RESULTS: 279 potentially eligible studies were identified. Only four studies were
      analysed further but none of these met the inclusion criteria and all were
      excluded from this review. CONCLUSIONS: There are no published randomised
      controlled clinical trials relevant to this review question. There is therefore a
      need for methodologically sound randomised controlled clinical trials that are
      reported according to the Consolidated Standards of Reporting Trials (CONSORT)
      statement (www.consort-statement.org/). Further research also needs to explore
      qualitatively the views of patients on repairing versus replacement and
      investigate themes around pain, distress and anxiety, time and costs.

PMID- 21170014
TI  - How common is tooth pain after root canal treatment?
AB  - DATA SOURCES: Medline, the Cochrane Library, TRIP database and Google Scholar,
      hand searching of articles, reviews and textbooks. STUDY SELECTION: Articles in
      any language about endodontic procedures, (initial treatment or retreatment and
      surgical or nonsurgical but not pulpotomy, partial pulpectomy or pulp capping) in
      permanent teeth that reported on pain at a minimum of six months were included.
      The main outcome was the presence of all-cause pain, with no differentiation on
      the basis of aetiologies. The outcome of all-cause pain was considered positive
      if reported by either the patient or the practitioner. Pain could be spontaneous
      or provoked by biting, palpation or percussion. DATA EXTRACTION AND SYNTHESIS:
      Data were extracted independently by two reviewers and STROBE criteria
      (www.strobe-statement.org) used to assess quality. A summary estimate of
      persistent all-cause pain frequency was established by using a random-effects
      meta-analysis. The influence of treatment approach (surgical/nonsurgical),
      longitudinal study design (prospective/retrospective), follow-up rate and
      duration, initial treatment versus retreatment, and quality of reporting on the
      pain frequency estimate was assessed in subgroup analyses. RESULTS: 26 studies
      that included 5777 teeth with 2996 (51.9%) having follow-up pain information met
      the inclusion criteria. 168 teeth with pain were identified giving a frequency of
      5.3% (95% confidence interval, 3.5%-7.2%, p < 0.001) for persistent all-cause
      pain. High and statistically significant heterogeneity among studies (I(2) = 80%)
      was present. In subgroup analysis, prospective studies had a higher pain
      frequency (7.6%) than retrospectives studies (0.9%). Quality of study reporting
      was identified as the most influential reason for study heterogeneity.
      CONCLUSIONS: The frequency of all-cause persistent pain after endodontic
      procedures was estimated to be 5.3%, with higher report quality studies
      suggesting >7%.

PMID- 21170015
TI  - Midpalatal implants for orthodontic anchorage.
AB  - DESIGN: Randomised controlled trial. INTERVENTION: Patients with various
      malocclusions in which any forward movement of the molars would prevent
      achievement of an ideal Class I canine relationship were randomly allocated to
      either the headgear or the implant group. Randomisation was carried out by using
      a block design and computer-generated random numbers. The allocations were
      concealed in consecutively numbered, sealed envelopes. OUTCOME MEASURE: The
      outcomes were; surgical and orthodontic success rates of the implants, the number
      of visits, the length of treatment time and the success of treatment as judged by
      the peer assessment rating (PAR) score reductions and the patients' attitudes to
      implant placement. RESULTS: The surgical success rate of the implants was 75% and
      the orthodontic success rate was more than 90%. Both implants and headgear proved
      to be effective methods of reinforcing anchorage. The total number of visits was
      greater in the implant group, but the overall treatment times were almost
      identical. There were no statistically significant differences between the 2
      groups in PAR scores either at the start or the end of treatment, and the
      percentages of PAR score reductions were almost identical. The patients had no
      problems accepting midpalatal implants as a method of reinforcing anchorage.
      CONCLUSIONS: The use of palatal implants to reinforce anchorage was as effective
      as extraoral anchorage with headgear.

PMID- 21170016
TI  - Indirect or direct restorations for heavily restored posterior adult teeth?
AB  - CLINICAL BOTTOM LINE: There is no high quality evidence that supports or rejects
      the practice of placing a crown or onlay on a vital posterior tooth rather than a
      composite or amalgam restoration to ensure longer tooth survival.

PMID- 21170017
TI  - Understanding statistics 3.

PMID- 21170019
TI  - RE: Commentary 'Weak evidence to support benefit of periodontal maintenance
      therapy in prevention of tooth loss'. Evidence-Based Dentistry (2010) 11, 75-76.

PMID- 21170021
TI  - Activation of the Raf-MEK-ERK pathway is required for neutrophil extracellular
      trap formation.
AB  - The signaling mechanisms leading to the formation of neutrophil extracellular
      traps (NETs), relevant in infections, sepsis and autoimmune diseases, are poorly
      understood. Neutrophils are not amenable to studies with conventional genetic
      techniques. Using a new chemical genetic analysis we show that the Raf-MEK-ERK
      pathway is involved in NET formation through activation of NADPH oxidase and
      upregulation of antiapoptotic proteins. We identify potential targets for drugs
      addressing NET-associated diseases.

PMID- 21170022
TI  - Spatially asymmetric reorganization of inhibition establishes a motion-sensitive
      circuit.
AB  - Spatial asymmetries in neural connectivity have an important role in creating
      basic building blocks of neuronal processing. A key circuit module of
      directionally selective (DS) retinal ganglion cells is a spatially asymmetric
      inhibitory input from starburst amacrine cells. It is not known how and when this
      circuit asymmetry is established during development. Here we photostimulate mouse
      starburst cells targeted with channelrhodopsin-2 (refs 6-8) while recording from
      a single genetically labelled type of DS cell. We follow the spatial distribution
      of synaptic strengths between starburst and DS cells during early postnatal
      development before these neurons can respond to a physiological light stimulus,
      and confirm connectivity by monosynaptically restricted trans-synaptic rabies
      viral tracing. We show that asymmetry develops rapidly over a 2-day period
      through an intermediate state in which random or symmetric synaptic connections
      have been established. The development of asymmetry involves the spatially
      selective reorganization of inhibitory synaptic inputs. Intriguingly, the spatial
      distribution of excitatory synaptic inputs from starburst cells is significantly
      more symmetric than that of the inhibitory inputs at the end of this
      developmental period. Our work demonstrates a rapid developmental switch from a
      symmetric to asymmetric input distribution for inhibition in the neural circuit
      of a principal cell.

PMID- 21170024
TI  - Calm in a crisis.

PMID- 21170023
TI  - The assembly of a GTPase-kinase signalling complex by a bacterial catalytic
      scaffold.
AB  - The fidelity and specificity of information flow within a cell is controlled by
      scaffolding proteins that assemble and link enzymes into signalling circuits.
      These circuits can be inhibited by bacterial effector proteins that post
      translationally modify individual pathway components. However, there is emerging
      evidence that pathogens directly organize higher-order signalling networks
      through enzyme scaffolding, and the identity of the effectors and their
      mechanisms of action are poorly understood. Here we identify the
      enterohaemorrhagic Escherichia coli O157:H7 type III effector EspG as a regulator
      of endomembrane trafficking using a functional screen, and report ADP
      ribosylation factor (ARF) GTPases and p21-activated kinases (PAKs) as its
      relevant host substrates. The 2.5 A crystal structure of EspG in complex with
      ARF6 shows how EspG blocks GTPase-activating-protein-assisted GTP hydrolysis,
      revealing a potent mechanism of GTPase signalling inhibition at organelle
      membranes. In addition, the 2.8 A crystal structure of EspG in complex with the
      autoinhibitory Ialpha3-helix of PAK2 defines a previously unknown catalytic site
      in EspG and provides an allosteric mechanism of kinase activation by a bacterial
      effector. Unexpectedly, ARF and PAKs are organized on adjacent surfaces of EspG,
      indicating its role as a 'catalytic scaffold' that effectively reprograms
      cellular events through the functional assembly of GTPase-kinase signalling
      complex.

PMID- 21170025
TI  - Stand up for science.

PMID- 21170026
TI  - Rapid evolutionary innovation during an Archaean genetic expansion.
AB  - The natural history of Precambrian life is still unknown because of the rarity of
      microbial fossils and biomarkers. However, the composition of modern-day genomes
      may bear imprints of ancient biogeochemical events. Here we use an explicit model
      of macroevolution including gene birth, transfer, duplication and loss events to
      map the evolutionary history of 3,983 gene families across the three domains of
      life onto a geological timeline. Surprisingly, we find that a brief period of
      genetic innovation during the Archaean eon, which coincides with a rapid
      diversification of bacterial lineages, gave rise to 27% of major modern gene
      families. A functional analysis of genes born during this Archaean expansion
      reveals that they are likely to be involved in electron-transport and respiratory
      pathways. Genes arising after this expansion show increasing use of molecular
      oxygen (P = 3.4 * 10(-8)) and redox-sensitive transition metals and compounds,
      which is consistent with an increasingly oxygenating biosphere.

PMID- 21170028
TI  - Room-temperature sub-diffraction-limited plasmon laser by total internal
      reflection.
AB  - Plasmon lasers are a new class of coherent optical amplifiers that generate and
      sustain light well below its diffraction limit. Their intense, coherent and
      confined optical fields can enhance significantly light-matter interactions and
      bring fundamentally new capabilities to bio-sensing, data storage,
      photolithography and optical communications. However, metallic plasmon laser
      cavities generally exhibit both high metal and radiation losses, limiting the
      operation of plasmon lasers to cryogenic temperatures, where sufficient gain can
      be attained. Here, we present a room-temperature semiconductor sub-diffraction
      limited laser by adopting total internal reflection of surface plasmons to
      mitigate the radiation loss, while using hybrid semiconductor-insulator-metal
      nanosquares for strong confinement with low metal loss. High cavity quality
      factors, approaching 100, along with strong lambda/20 mode confinement, lead to
      enhancements of spontaneous emission rate by up to 18-fold. By controlling the
      structural geometry we reduce the number of cavity modes to achieve single-mode
      lasing.

PMID- 21170027
TI  - IL-1beta-driven neutrophilia preserves antibacterial defense in the absence of
      the kinase IKKbeta.
AB  - Transcription factor NF-kappaB and its activating kinase IKKbeta are associated
      with inflammation and are believed to be critical for innate immunity. Despite
      the likelihood of immune suppression, pharmacological blockade of IKKbeta-NF
      kappaB has been considered as a therapeutic strategy. However, we found
      neutrophilia in mice with inducible deletion of IKKbeta (Ikkbeta(Delta) mice).
      These mice had hyperproliferative granulocyte-macrophage progenitors and
      pregranulocytes and a prolonged lifespan of mature neutrophils that correlated
      with the induction of genes encoding prosurvival molecules. Deletion of
      interleukin 1 receptor 1 (IL-1R1) in Ikkbeta(Delta) mice normalized blood
      cellularity and prevented neutrophil-driven inflammation. However,
      Ikkbeta(Delta)Il1r1(-/-) mice, unlike Ikkbeta(Delta) mice, were highly
      susceptible to bacterial infection, which indicated that signaling via IKKbeta-NF
      kappaB or IL-1R1 can maintain antimicrobial defenses in each other's absence,
      whereas inactivation of both pathways severely compromises innate immunity.

PMID- 21170030
TI  - Collective cell migration requires suppression of actomyosin at cell-cell
      contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6.
AB  - Collective cell migration occurs in a range of contexts: cancer cells frequently
      invade in cohorts while retaining cell-cell junctions. Here we show that
      collective invasion by cancer cells depends on decreasing actomyosin
      contractility at sites of cell-cell contact. When actomyosin is not downregulated
      at cell-cell contacts, migrating cells lose cohesion. We provide a molecular
      mechanism for this downregulation. Depletion of discoidin domain receptor 1
      (DDR1) blocks collective cancer-cell invasion in a range of two-dimensional,
      three-dimensional and 'organotypic' models. DDR1 coordinates the Par3/Par6 cell
      polarity complex through its carboxy terminus, binding PDZ domains in Par3 and
      Par6. The DDR1-Par3/Par6 complex controls the localization of RhoE to cell-cell
      contacts, where it antagonizes ROCK-driven actomyosin contractility. Depletion of
      DDR1, Par3, Par6 or RhoE leads to increased actomyosin contactility at cell-cell
      contacts, a loss of cell-cell cohesion and defective collective cell invasion.

PMID- 21170031
TI  - The E3 ubiquitin ligase Wwp2 regulates craniofacial development through mono
      ubiquitylation of Goosecoid.
AB  - Craniofacial anomalies (CFAs) are the most frequently occurring human congenital
      disease, and a major cause of infant mortality and childhood morbidity. Although
      CFAs seems to arise from a combination of genetic factors and environmental
      influences, the underlying gene defects and pathophysiological mechanisms for
      most CFAs are currently unknown. Here we reveal a role for the E3 ubiquitin
      ligase Wwp2 in regulating craniofacial patterning. Mice deficient in Wwp2 develop
      malformations of the craniofacial region. Wwp2 is present in cartilage where its
      expression is controlled by Sox9. Our studies demonstrate that Wwp2 influences
      craniofacial patterning through its interactions with Goosecoid (Gsc), a paired
      like homeobox transcription factor that has an important role in craniofacial
      development. We show that Wwp2-associated Gsc is a transcriptional activator of
      the key cartilage regulatory protein Sox6. Wwp2 interacts with Gsc to facilitate
      its mono-ubiquitylation, a post-translational modification required for optimal
      transcriptional activation of Gsc. Our results identify for the first time a
      physiological pathway regulated by Wwp2 in vivo, and also a unique non
      proteolytic mechanism through which Wwp2 controls craniofacial development.

PMID- 21170032
TI  - Loss of the RhoGAP SRGP-1 promotes the clearance of dead and injured cells in
      Caenorhabditis elegans.
AB  - Multicellular animals rapidly clear dying cells from their bodies. Many of the
      pathways that mediate this cell removal are conserved through evolution. Here, we
      identify srgp-1 as a negative regulator of cell clearance in both Caenorhabditis
      elegans and mammalian cells. Loss of srgp-1 function results in improved
      engulfment of apoptotic cells, whereas srgp-1 overexpression inhibits apoptotic
      cell corpse removal. We show that SRGP-1 functions in engulfing cells and
      functions as a GTPase activating protein (GAP) for CED-10 (Rac1). Interestingly,
      loss of srgp-1 function promotes not only the clearance of already dead cells,
      but also the removal of cells that have been brought to the verge of death
      through sublethal apoptotic, necrotic or cytotoxic insults. In contrast, impaired
      engulfment allows damaged cells to escape clearance, which results in increased
      long-term survival. We propose that C. elegans uses the engulfment machinery as
      part of a primitive, but evolutionarily conserved, survey mechanism that
      identifies and removes unfit cells within a tissue.

PMID- 21170033
TI  - Direct visualization of the co-transcriptional assembly of a nuclear body by
      noncoding RNAs.
AB  - The cell nucleus is a highly compartmentalized organelle harbouring a variety of
      dynamic membraneless nuclear bodies. How these subnuclear domains are established
      and maintained is not well understood. Here, we investigate the molecular
      mechanism of how one nuclear body, the paraspeckle, is assembled and organized.
      Paraspeckles are discrete ribonucleoprotein bodies found in mammalian cells and
      implicated in nuclear retention of hyperedited mRNAs. We developed a live-cell
      imaging system that allows for the inducible transcription of Men E/beta (also
      known as Neat1; ref. 12) noncoding RNAs (ncRNAs) and the direct visualization of
      the recruitment of paraspeckle proteins. Using this system, we demonstrate that
      Men E/beta ncRNAs are essential to initiate the de novo assembly of paraspeckles.
      These newly formed structures effectively harbour nuclear-retained mRNAs
      confirming that they are bona fide functional paraspeckles. By three independent
      approaches, we show that it is the act of Men E/beta transcription, but not
      ncRNAs alone, that regulates paraspeckle maintenance. Finally, fluorescence
      recovery after photobleaching (FRAP) analyses supported a critical structural
      role for Men E/beta ncRNAs in paraspeckle organization. This study establishes a
      model in which Men E/beta ncRNAs serve as a platform to recruit proteins to
      assemble paraspeckles.

PMID- 21170034
TI  - TSPYL5 suppresses p53 levels and function by physical interaction with USP7.
AB  - We have previously reported a gene expression signature that is a powerful
      predictor of poor clinical outcome in breast cancer. Among the seventy genes in
      this expression profile is a gene of unknown function: TSPYL5 (TSPY-like 5, also
      known as KIAA1750). TSPYL5 is located within a small region at chromosome 8q22
      that is frequently amplified in breast cancer, which suggests that TSPYL5 has a
      causal role in breast oncogenesis. Here, we report that high TSPYL5 expression is
      an independent marker of poor outcome in breast cancer. Mass spectrometric
      analysis revealed that TSPYL5 interacts with ubiquitin-specific protease 7 (USP7;
      also known as herpesvirus-associated ubiquitin-specific protease; HAUSP). USP7 is
      the deubiquitylase for the p53 tumour suppressor and TSPYL5 reduces the activity
      of USP7 towards p53, resulting in increased p53 ubiquitylation. We demonstrate
      that TSPYL5 reduces p53 protein levels and inhibits activation of p53-target
      genes. Furthermore, expression of TSPYL5 overrides p53-dependent proliferation
      arrest and oncogene-induced senescence, and contributes to oncogenic
      transformation in multiple cell-based assays. Our data identify TSPYL5 as a
      suppressor of p53 function through its interaction with USP7.

PMID- 21170035
TI  - HoxA3 is an apical regulator of haemogenic endothelium.
AB  - During development, haemogenesis occurs invariably at sites of vasculogenesis.
      Between embryonic day (E) 9.5 and E10.5 in mice, endothelial cells in the caudal
      part of the dorsal aorta generate haematopoietic stem cells and are referred to
      as haemogenic endothelium. The mechanisms by which haematopoiesis is restricted
      to this domain, and how the morphological transformation from endothelial to
      haematopoietic is controlled are unknown. We show here that HoxA3, a gene
      uniquely expressed in the embryonic but not yolk sac vasculature, restrains
      haematopoietic differentiation of the earliest endothelial progenitors, and
      induces reversion of the earliest haematopoietic progenitors into CD41-negative
      endothelial cells. This reversible modulation of endothelial-haematopoietic state
      is accomplished by targeting key haematopoietic transcription factors for
      downregulation, including Runx1, Gata1, Gfi1B, Ikaros, and PU.1. Through loss-of
      function, and gain-of-function epistasis experiments, and the identification of
      antipodally regulated targets, we show that among these factors, Runx1 is
      uniquely able to erase the endothelial program set up by HoxA3. These results
      suggest both why a frank endothelium does not precede haematopoiesis in the yolk
      sac, and why haematopoietic stem cell generation requires Runx1 expression only
      in endothelial cells.

PMID- 21170037
TI  - Nanoparticle-induced unfolding of fibrinogen promotes Mac-1 receptor activation
      and inflammation.
AB  - The chemical composition, size, shape and surface characteristics of
      nanoparticles affect the way proteins bind to these particles, and this in turn
      influences the way in which nanoparticles interact with cells and tissues.
      Nanomaterials bound with proteins can result in physiological and pathological
      changes, including macrophage uptake, blood coagulation, protein aggregation and
      complement activation, but the mechanisms that lead to these changes remain
      poorly understood. Here, we show that negatively charged poly(acrylic acid)
      conjugated gold nanoparticles bind to and induce unfolding of fibrinogen, which
      promotes interaction with the integrin receptor, Mac-1. Activation of this
      receptor increases the NF-kappaB signalling pathway, resulting in the release of
      inflammatory cytokines. However, not all nanoparticles that bind to fibrinogen
      demonstrated this effect. Our results show that the binding of certain
      nanoparticles to fibrinogen in plasma offers an alternative mechanism to the more
      commonly described role of oxidative stress in the inflammatory response to
      nanomaterials.

PMID- 21170036
TI  - Fates-shifted is an F-box protein that targets Bicoid for degradation and
      regulates developmental fate determination in Drosophila embryos.
AB  - Bicoid (Bcd) is a morphogenetic protein that instructs patterning along the
      anterior-posterior (A-P) axis in Drosophila melanogaster embryos. Despite
      extensive studies, what controls the formation of a normal concentration gradient
      of Bcd remains an unresolved and controversial question. Here, we show that Bcd
      protein degradation is mediated by the ubiquitin-proteasome pathway. We have
      identified an F-box protein, encoded by fates-shifted (fsd), that has an
      important role in Bcd protein degradation by targeting it for ubiquitylation.
      Embryos from females lacking fsd have an altered Bcd gradient profile, resulting
      in a shift of the fatemap along the A-P axis. Our study is an experimental
      demonstration that, contrary to an alternative hypothesis, Bcd protein
      degradation is required for normal gradient formation and developmental fate
      determination.

PMID- 21170038
TI  - Single-walled carbon nanotubes as excitonic optical wires.
AB  - Although metallic nanostructures are useful for nanoscale optics, all of their
      key optical properties are determined by their geometry. This makes it difficult
      to adjust these properties independently, and can restrict applications. Here we
      use the absolute intensity of Rayleigh scattering to show that single-walled
      carbon nanotubes can form ideal optical wires. The spatial distribution of the
      radiation scattered by the nanotubes is determined by their shape, but the
      intensity and spectrum of the scattered radiation are determined by exciton
      dynamics, quantum-dot-like optical resonances and other intrinsic properties.
      Moreover, the nanotubes display a uniform peak optical conductivity of
      approximately 8 e(2)/h, which we derive using an exciton model, suggesting
      universal behaviour similar to that observed in nanotube conductance. We further
      demonstrate a radiative coupling between two distant nanotubes, with potential
      applications in metamaterials and optical antennas.

PMID- 21170039
TI  - Quantum oscillations in magnetically doped colloidal nanocrystals.
AB  - Progress in the synthesis of colloidal quantum dots has recently provided access
      to entirely new forms of diluted magnetic semiconductors, some of which may find
      use in quantum computation. The usefulness of a spin qubit is defined by its Rabi
      frequency, which determines the operation time, and its coherence time, which
      sets the error correction window. However, the spin dynamics of magnetic impurity
      ions in colloidal doped quantum dots remain entirely unexplored. Here, we use
      pulsed electron paramagnetic resonance spectroscopy to demonstrate long spin
      coherence times of ~0.9 us in colloidal ZnO quantum dots containing the
      paramagnetic dopant Mn(2+), as well as Rabi oscillations with frequencies ranging
      between 2 and 20 MHz depending on microwave power. We also observe electron spin
      echo envelope modulations of the Mn(2+) signal due to hyperfine coupling with
      protons outside the quantum dots, a situation unique to the colloidal form of
      quantum dots, and not observed to date.

PMID- 21170040
TI  - Large intrinsic energy bandgaps in annealed nanotube-derived graphene
      nanoribbons.
AB  - The usefulness of graphene for electronics has been limited because it does not
      have an energy bandgap. Although graphene nanoribbons have non-zero bandgaps,
      lithographic fabrication methods introduce defects that decouple the bandgap from
      electronic properties, compromising performance. Here we report direct
      measurements of a large intrinsic energy bandgap of approximately 50 meV in
      nanoribbons (width, approximately 100 nm) fabricated by high-temperature hydrogen
      annealing of unzipped carbon nanotubes. The thermal energy required to promote a
      charge to the conduction band (the activation energy) is measured to be seven
      times greater than in lithographically defined nanoribbons, and is close to the
      width of the voltage range over which differential conductance is zero (the
      transport gap). This similarity suggests that the activation energy is in fact
      the intrinsic energy bandgap. High-resolution transmission electron and Raman
      microscopy, in combination with an absence of hopping conductance and stochastic
      charging effects, suggest a low defect density.

PMID- 21170041
TI  - Biomagnification of cadmium selenide quantum dots in a simple experimental
      microbial food chain.
AB  - Previous studies have shown that engineered nanomaterials can be transferred from
      prey to predator, but the ecological impacts of this are mostly unknown. In
      particular, it is not known if these materials can be biomagnified-a process in
      which higher concentrations of materials accumulate in organisms higher up in the
      food chain. Here, we show that bare CdSe quantum dots that have accumulated in
      Pseudomonas aeruginosa bacteria can be transferred to and biomagnified in the
      Tetrahymena thermophila protozoa that prey on the bacteria. Cadmium
      concentrations in the protozoa predator were approximately five times higher than
      their bacterial prey. Quantum-dot-treated bacteria were differentially toxic to
      the protozoa, in that they inhibited their own digestion in the protozoan food
      vacuoles. Because the protozoa did not lyse, largely intact quantum dots remain
      available to higher trophic levels. The observed biomagnification from bacterial
      prey is significant because bacteria are at the base of environmental food webs.
      Our findings illustrate the potential for biomagnification as an ecological
      impact of nanomaterials.

PMID- 21170042
TI  - Haplotype-resolved genome sequencing of a Gujarati Indian individual.
AB  - Haplotype information is essential to the complete description and interpretation
      of genomes, genetic diversity and genetic ancestry. Although individual human
      genome sequencing is increasingly routine, nearly all such genomes are unresolved
      with respect to haplotype. Here we combine the throughput of massively parallel
      sequencing with the contiguity information provided by large-insert cloning to
      experimentally determine the haplotype-resolved genome of a South Asian
      individual. A single fosmid library was split into a modest number of pools, each
      providing ~3% physical coverage of the diploid genome. Sequencing of each pool
      yielded reads overwhelmingly derived from only one homologous chromosome at any
      given location. These data were combined with whole-genome shotgun sequence to
      directly phase 94% of ascertained heterozygous single nucleotide polymorphisms
      (SNPs) into long haplotype blocks (N50 of 386 kilobases (kbp)). This method also
      facilitates the analysis of structural variation, for example, to anchor novel
      insertions to specific locations and haplotypes.

PMID- 21170043
TI  - Whole-genome molecular haplotyping of single cells.
AB  - Conventional experimental methods of studying the human genome are limited by the
      inability to independently study the combination of alleles, or haplotype, on
      each of the homologous copies of the chromosomes. We developed a microfluidic
      device capable of separating and amplifying homologous copies of each chromosome
      from a single human metaphase cell. Single-nucleotide polymorphism (SNP) array
      analysis of amplified DNA enabled us to achieve completely deterministic, whole
      genome, personal haplotypes of four individuals, including a HapMap trio with
      European ancestry (CEU) and an unrelated European individual. The phases of
      alleles were determined at ~99.8% accuracy for up to ~96% of all assayed SNPs. We
      demonstrate several practical applications, including direct observation of
      recombination events in a family trio, deterministic phasing of deletions in
      individuals and direct measurement of the human leukocyte antigen haplotypes of
      an individual. Our approach has potential applications in personal genomics,
      single-cell genomics and statistical genetics.

PMID- 21170044
TI  - Common variants in P2RY11 are associated with narcolepsy.
AB  - Growing evidence supports the hypothesis that narcolepsy with cataplexy is an
      autoimmune disease. We here report genome-wide association analyses for
      narcolepsy with replication and fine mapping across three ethnic groups (3,406
      individuals of European ancestry, 2,414 Asians and 302 African Americans). We
      identify a SNP in the 3' untranslated region of P2RY11, the purinergic receptor
      subtype P2Y11 gene, which is associated with narcolepsy (rs2305795, combined P =
      6.1 * 10-10, odds ratio = 1.28, 95% CI 1.19-1.39, n = 5689). The disease
      associated allele is correlated with reduced expression of P2RY11 in CD8(+) T
      lymphocytes (339% reduced, P = 0.003) and natural killer (NK) cells (P = 0.031),
      but not in other peripheral blood mononuclear cell types. The low expression
      variant is also associated with reduced P2RY11-mediated resistance to ATP-induced
      cell death in T lymphocytes (P = 0.0007) and natural killer cells (P = 0.001).
      These results identify P2RY11 as an important regulator of immune-cell survival,
      with possible implications in narcolepsy and other autoimmune diseases.

PMID- 21170045
TI  - Histamine deficiency promotes inflammation-associated carcinogenesis through
      reduced myeloid maturation and accumulation of CD11b+Ly6G+ immature myeloid
      cells.
AB  - Histidine decarboxylase (HDC), the unique enzyme responsible for histamine
      generation, is highly expressed in myeloid cells, but its function in these cells
      is poorly understood. Here we show that Hdc-knockout mice show a high rate of
      colon and skin carcinogenesis. Using Hdc-EGFP bacterial artificial chromosome
      (BAC) transgenic mice in which EGFP expression is controlled by the Hdc promoter,
      we show that Hdc is expressed primarily in CD11b(+)Ly6G(+) immature myeloid cells
      (IMCs) that are recruited early on in chemical carcinogenesis. Transplant of Hdc
      deficient bone marrow to wild-type recipients results in increased
      CD11b(+)Ly6G(+) cell mobilization and reproduces the cancer susceptibility
      phenotype of Hdc-knockout mice. In addition, Hdc-deficient IMCs promote the
      growth of tumor allografts, whereas mouse CT26 colon cancer cells downregulate
      Hdc expression through promoter hypermethylation and inhibit myeloid cell
      maturation. Exogenous histamine induces the differentiation of IMCs and
      suppresses their ability to support the growth of tumor allografts. These data
      indicate key roles for Hdc and histamine in myeloid cell differentiation and
      CD11b(+)Ly6G(+) IMCs in early cancer development.

PMID- 21170046
TI  - Detrimental effects of adenosine signaling in sickle cell disease.
AB  - Hypoxia can act as an initial trigger to induce erythrocyte sickling and eventual
      end organ damage in sickle cell disease (SCD). Many factors and metabolites are
      altered in response to hypoxia and may contribute to the pathogenesis of the
      disease. Using metabolomic profiling, we found that the steady-state
      concentration of adenosine in the blood was elevated in a transgenic mouse model
      of SCD. Adenosine concentrations were similarly elevated in the blood of humans
      with SCD. Increased adenosine levels promoted sickling, hemolysis and damage to
      multiple tissues in SCD transgenic mice and promoted sickling of human
      erythrocytes. Using biochemical, genetic and pharmacological approaches, we
      showed that adenosine A(2B) receptor (A(2B)R)-mediated induction of 2,3
      diphosphoglycerate, an erythrocyte-specific metabolite that decreases the oxygen
      binding affinity of hemoglobin, underlies the induction of erythrocyte sickling
      by excess adenosine both in cultured human red blood cells and in SCD transgenic
      mice. Thus, excessive adenosine signaling through the A(2B)R has a pathological
      role in SCD. These findings may provide new therapeutic possibilities for this
      disease.

PMID- 21170047
TI  - Paraoxonase-1 is a major determinant of clopidogrel efficacy.
AB  - Clinical efficacy of the antiplatelet drug clopidogrel is hampered by its
      variable biotransformation into the active metabolite. The variability in the
      clinical response to clopidogrel treatment has been attributed to genetic
      factors, but the specific genes and mechanisms underlying clopidogrel
      bioactivation remain unclear. Using in vitro metabolomic profiling techniques, we
      identified paraoxonase-1 (PON1) as the crucial enzyme for clopidogrel
      bioactivation, with its common Q192R polymorphism determining the rate of active
      metabolite formation. We tested the clinical relevance of the PON1 Q192R genotype
      in a population of individuals with coronary artery disease who underwent stent
      implantation and received clopidogrel therapy. PON1 QQ192 homozygous individuals
      showed a considerably higher risk than RR192 homozygous individuals of stent
      thrombosis, lower PON1 plasma activity, lower plasma concentrations of active
      metabolite and lower platelet inhibition. Thus, we identified PON1 as a key
      factor for the bioactivation and clinical activity of clopidogrel. These findings
      have therapeutic implications and may be exploited to prospectively assess the
      clinical efficacy of clopidogrel.

PMID- 21170048
TI  - Differentiation between glioma and radiation necrosis using molecular magnetic
      resonance imaging of endogenous proteins and peptides.
AB  - It remains difficult to distinguish tumor recurrence from radiation necrosis
      after brain tumor therapy. Here we show that these lesions can be distinguished
      using the amide proton transfer (APT) magnetic resonance imaging (MRI) signals of
      endogenous cellular proteins and peptides as an imaging biomarker. When comparing
      two models of orthotopic glioma (SF188/V+ glioma and 9L gliosarcoma) with a model
      of radiation necrosis in rats, we could clearly differentiate viable glioma
      (hyperintense) from radiation necrosis (hypointense to isointense) by APT MRI.
      When we irradiated rats with U87MG gliomas, the APT signals in the irradiated
      tumors had decreased substantially by 3 d and 6 d after radiation. The amide
      protons that can be detected by APT provide a unique and noninvasive MRI
      biomarker for distinguishing viable malignancy from radiation necrosis and
      predicting tumor response to therapy.

PMID- 21170049
TI  - Conformational changes in Dnm1 support a contractile mechanism for mitochondrial
      fission.
AB  - Mitochondria are dynamic organelles that undergo cycles of fission and fusion.
      The yeast dynamin-related protein Dnm1 has been localized to sites of
      mitochondrial division. Using cryo-EM, we have determined the three-dimensional
      (3D) structure of Dnm1 in a GTP-bound state. The 3D map showed that Dnm1 adopted
      a unique helical assembly when compared with dynamin, which is involved in
      vesicle scission during endocytosis. Upon GTP hydrolysis, Dnm1 constricted
      liposomes and subsequently dissociated from the lipid bilayer. The magnitude of
      Dnm1 constriction was substantially larger than the decrease in diameter
      previously reported for dynamin. We postulate that the larger conformational
      change is mediated by a flexible Dnm1 structure that has limited interaction with
      the underlying bilayer. Our structural studies support the idea that Dnm1 has a
      mechanochemical role during mitochondrial division.

PMID- 21170050
TI  - Mapping the sequence of conformational changes underlying selectivity filter
      gating in the K(v)11.1 potassium channel.
AB  - The potassium channel selectivity filter both discriminates between K(+) and
      sodium ions and contributes to gating of ion flow. Static structures of
      conducting (open) and nonconducting (inactivated) conformations of this filter
      are known; however, the sequence of protein rearrangements that connect these two
      states is not. We show that closure of the selectivity filter gate in the human
      K(v)11.1 K(+) channel (also known as hERG, for ether-a-go-go-related gene), a key
      regulator of the rhythm of the heartbeat, is initiated by K(+) exit, followed in
      sequence by conformational rearrangements of the pore domain outer helix,
      extracellular turret region, voltage sensor domain, intracellular domains and
      pore domain inner helix. In contrast to the simple wave-like sequence of events
      proposed for opening of ligand-gated ion channels, a complex spatial and temporal
      sequence of widespread domain motions connect the open and inactivated states of
      the K(v)11.1 K(+) channel.

PMID- 21170051
TI  - Mixed Hsp90-cochaperone complexes are important for the progression of the
      reaction cycle.
AB  - The chaperone cycle of heat shock protein-90 (Hsp90) involves progression through
      defined complexes with different cochaperones. It is still enigmatic how the
      exchange of cochaperones is regulated. The first cochaperone entering the cycle
      is the Hsp90 ATPase inhibitor Sti1 (Hop in human), which later is replaced by a
      prolyl isomerase (PPIase) and p23. We found, unexpectedly, that one Sti1 molecule
      is sufficient to completely inhibit the ATPase of the Hsp90 dimer. Upon addition
      of a PPIase cochaperone to the Hsp90-Sti1 complex, an asymmetric ternary complex
      is preferentially formed. This PPIase-Hsp90-Sti1 intermediate is important for
      the progression of the cycle. To expel the bound Sti1, the concerted action of
      ATP and p23 is required. This mechanism, which is strictly conserved between the
      yeast and human Hsp90 systems, presents an example of how, in a cyclic process,
      directionality of assembly and disassembly of protein complexes can be achieved.

PMID- 21170052
TI  - P2X receptor channels show threefold symmetry in ionic charge selectivity and
      unitary conductance.
AB  - In the closed structure of the P2X cation channel, three alpha-helical
      transmembrane domains cross the membrane obliquely. In rat P2X2 receptors, these
      intersect at Thr(339). Replacing Thr(339) by lysine in one, two or three subunits
      progressively increased chloride permeability and reduced unitary conductance.
      This implies that the closed-open transition involves a symmetrical separation of
      the three subunits and that Thr(339) from each subunit contributes symmetrically
      to the open channel permeation pathway.

PMID- 21170053
TI  - Thalamic interneurons and relay cells use complementary synaptic mechanisms for
      visual processing.
AB  - Synapses made by local interneurons dominate the thalamic circuits that process
      signals traveling from the eye downstream. The anatomical and physiological
      differences between interneurons and the (relay) cells that project to cortex are
      vast. To explore how these differences might influence visual processing, we made
      intracellular recordings from both classes of cells in vivo in cats.
      Macroscopically, all receptive fields were similar, consisting of two
      concentrically arranged subregions in which dark and bright stimuli elicited
      responses of the reverse sign. Microscopically, however, the responses of the two
      types of cells had opposite profiles. Excitatory stimuli drove trains of single
      excitatory postsynaptic potentials in relay cells, but graded depolarizations in
      interneurons. Conversely, suppressive stimuli evoked smooth hyperpolarizations in
      relay cells and unitary inhibitory postsynaptic potentials in interneurons.
      Computational analyses suggested that these complementary patterns of response
      help to preserve information encoded in the fine timing of retinal spikes and to
      increase the amount of information transmitted to cortex.

PMID- 21170054
TI  - Ca(2+)-dependent enhancement of release by subthreshold somatic depolarization.
AB  - In many neurons, subthreshold somatic depolarization can spread electrotonically
      into the axon and modulate subsequent spike-evoked transmission. Although release
      probability is regulated by intracellular Ca(2+), the Ca(2+) dependence of this
      modulatory mechanism has been debated. Using paired recordings from synaptically
      connected molecular layer interneurons (MLIs) of the rat cerebellum, we observed
      Ca(2+)-mediated strengthening of release following brief subthreshold
      depolarization of the soma. Two-photon microscopy revealed that, at the axon,
      somatic depolarization evoked Ca(2+) influx through voltage-sensitive Ca(2+)
      channels and facilitated spike-evoked Ca(2+) entry. Exogenous Ca(2+) buffering
      diminished these Ca(2+) transients and eliminated the strengthening of release.
      Axonal Ca(2+) entry elicited by subthreshold somatic depolarization also
      triggered asynchronous transmission that may deplete vesicle availability and
      thereby temper release strengthening. In this cerebellar circuit, activity
      dependent presynaptic plasticity depends on Ca(2+) elevations resulting from both
      sub- and suprathreshold electrical activity initiated at the soma.

PMID- 21170055
TI  - Characterization of the proteome, diseases and evolution of the human
      postsynaptic density.
AB  - We isolated the postsynaptic density from human neocortex (hPSD) and identified
      1,461 proteins. hPSD mutations cause 133 neurological and psychiatric diseases
      and were enriched in cognitive, affective and motor phenotypes underpinned by
      sets of genes. Strong protein sequence conservation in mammalian lineages,
      particularly in hub proteins, indicates conserved function and organization in
      primate and rodent models. The hPSD is an important structure for nervous system
      disease and behavior.

PMID- 21170056
TI  - The auditory cortex mediates the perceptual effects of acoustic temporal
      expectation.
AB  - When events occur at predictable instants, anticipation improves performance.
      Knowledge of event timing modulates motor circuits and thereby improves response
      speed. By contrast, the neuronal mechanisms that underlie changes in sensory
      perception resulting from expectation are not well understood. We developed a
      behavioral procedure for rats in which we manipulated expectations about sound
      timing. Valid expectations improved both the speed and the accuracy of the
      subjects' performance, indicating not only improved motor preparedness but also
      enhanced perception. Single-neuron recordings in primary auditory cortex showed
      enhanced representation of sounds during periods of heightened expectation.
      Furthermore, we found that activity in auditory cortex was causally linked to the
      performance of the task and that changes in the neuronal representation of sounds
      predicted performance on a trial-by-trial basis. Our results indicate that
      changes in neuronal representation as early as primary sensory cortex mediate the
      perceptual advantage conferred by temporal expectation.

PMID- 21170057
TI  - Exposure science will not increase protection of workers from asbestos-caused
      diseases: NIOSH fails to provide needed public health action and leadership.

PMID- 21170060
TI  - Sex and lifestyle drugs: the pursuit of the fountain of youth.

PMID- 21170063
TI  - Prescribing for the "Swedish Viagra man".

PMID- 21170064
TI  - Where cost, medical necessity, and morality meet: should US government insurance
      programs pay for erectile dysfunction drugs?
AB  - Spending for the three most popular phosphodiesterase (PDE) inhibitor drugs to
      treat erectile dysfunction (ED) tops $1 billion worldwide annually. Using
      Medicaid and Medicare Part D as examples, we explore here whether US government
      insurance programs with limited budgets should reimburse for this class of ED
      drugs and review the common bases for justifying and denying reimbursement. We
      conclude that the clinical usefulness and costs of such drugs should be the
      primary drivers of coverage decisions, not moral attitudes toward sexual
      performance.

PMID- 21170065
TI  - Insurance coverage for erectile dysfunction drugs.

PMID- 21170066
TI  - The use and abuse of prescription medication to facilitate or enhance sexual
      behavior among adolescents.
AB  - Adolescents naturally experience an increased interest in sexual behavior, but
      they usually lack much experience. Thus, any prescription medication that holds
      the potential to ease or facilitate sexual matters holds a unique allure.
      Widespread cultural awareness of medications to treat erectile dysfunction (ED)
      has combined with a recent trend toward increased adolescent prescription drug
      abuse to create unique challenges for industry, clinicians, and researchers.

PMID- 21170067
TI  - A curricular divide: basic pharmacology vs. clinical pharmacology.
AB  - Two current surveys of graduating medical students and/or recently graduated
      physicians from the United Kingdom raise significant concerns about the quality
      and quantity of clinical pharmacology instruction. Compared with the relative
      abundance of information about the instruction of basic pharmacology in US
      medical schools, little information exists about similar curricular content of
      clinical pharmacology. Here, we highlight this lack of information and encourage
      clinical pharmacology educators to address this curricular divide.

PMID- 21170068
TI  - Clinical pharmacology aspects of sex-related drug products.
AB  - Clinical pharmacology plays an important role in drug development, including
      evaluation of a drug's pharmacokinetics (PK), interaction potential, exposure
      response relationship, and pharmacogenomics (Table 1). Reviewers in the Office of
      Clinical Pharmacology at the US Food and Drug Administration (FDA) consider these
      issues to facilitate drug development and to ensure that drug products are safe
      and effective. This article highlights some of the important clinical
      pharmacology topics in the development of sex-related drug products.

PMID- 21170069
TI  - Why do we need a trial on the effects of testosterone therapy in older men?
AB  - Decreases in levels of sex hormones occur with aging. Observational studies have
      found associations of low testosterone concentrations in older men with adverse
      symptoms; however, these associations do not prove causality. Therefore, the
      question arises whether to treat older men whose serum testosterone is low. In
      2009, the Testosterone Trial (T Trial) was funded to examine the efficacy of
      therapy in 800 elderly men with low testosterone levels; potentially associated
      symptoms; and abnormalities in physical, sexual, or cognitive function or
      vitality.

PMID- 21170070
TI  - The good, the bad, and the ugly of sunscreens.
AB  - Sunscreens protect against sunburn, but there is no evidence that they protect
      against basal cell carcinoma or melanoma. Problems lie in the behavior of
      individuals who use sunscreens to stay out longer in the sun than they otherwise
      would. Vitamin D inhibition is, at this stage, unlikely due to insufficient use
      by individuals. Safety of sunscreens is a concern, and sunscreen companies have
      emotionally and inaccurately promoted the use of sunscreens.

PMID- 21170072
TI  - Making memories last: the synaptic tagging and capture hypothesis.
AB  - The synaptic tagging and capture hypothesis of protein synthesis-dependent long
      term potentiation asserts that the induction of synaptic potentiation creates
      only the potential for a lasting change in synaptic efficacy, but not the
      commitment to such a change. Other neural activity, before or after induction,
      can also determine whether persistent change occurs. Recent findings, leading us
      to revise the original hypothesis, indicate that the induction of a local,
      synapse-specific 'tagged' state and the expression of long-term potentiation are
      dissociable. Additional observations suggest that there are major differences in
      the mechanisms of functional and structural plasticity. These advances call for a
      revised theory that incorporates the specific molecular and structural processes
      involved. Addressing the physiological relevance of previous in vitro findings,
      new behavioural studies have experimentally translated the hypothesis to learning
      and the consolidation of newly formed memories.

PMID- 21170073
TI  - Emerging concepts for the dynamical organization of resting-state activity in the
      brain.
AB  - A broad body of experimental work has demonstrated that apparently spontaneous
      brain activity is not random. At the level of large-scale neural systems, as
      measured with functional MRI (fMRI), this ongoing activity reflects the
      organization of a series of highly coherent functional networks. These so-called
      resting-state networks (RSNs) closely relate to the underlying anatomical
      connectivity but cannot be understood in those terms alone. Here we review three
      large-scale neural system models of primate neocortex that emphasize the key
      contributions of local dynamics, signal transmission delays and noise to the
      emerging RSNs. We propose that the formation and dissolution of resting-state
      patterns reflects the exploration of possible functional network configurations
      around a stable anatomical skeleton.

PMID- 21170074
TI  - DMRT1 at the border between mitosis and meiosis.

PMID- 21170075
TI  - New WHO-reference limits-revolution or storm in a teapot?
AB  - Since release of the latest WHO manual with the new lower reference values of
      semen parameters, a lot of discussion has been raised about their usefulness and
      appropriateness for assessment of male fertility. As with the previous reference
      values the new limits do neither allow an andrological diagnosis based on
      nosological criteria nor clear-cut differentiation between fertility and sub
      /infertility. Therefore, considering the fact that fertility is a continuum, the
      new lower reference limits should not be overestimated. Most probably, more sperm
      function tests, such as determination of DNA integrity, and-in the future
      assessment of biomarkers, such as sperm proteomics will be included into
      andrological work-up, thus resulting in a more personalized approach of
      infertility management. On the other hand, the detailed instructions for standard
      and advanced semen analysis provided in the new manual are very much appreciated
      and should be adopted by each seriously working laboratory.

PMID- 21170076
TI  - Body mass index and serum lipid profile influence serum prostate-specific antigen
      in Chinese men younger than 50 years of age.
AB  - This study is to assess the potential factors that could affect the serum
      prostate-specific antigen (PSA) level in healthy younger men. We evaluated the
      associations of age, body mass index (BMI) and serum lipid profile with serum PSA
      level in 6774 Chinese men (aged 20-49 years) who received a routine health
      examination. Eligible men were classified into 10-year age groups. BMI was
      categorized as underweight (<18.5), normal (18.5-22.9), overweight (23.0-24.9),
      obese (25.0-29.9) and very obese (>30) according to the redefined World Health
      Organization (WHO) criteria for the Asia-Pacific region. PSA levels were compared
      among groups as well. In multiple linear regression analysis, PSA was positively
      correlated with age (P<0.0001). Negative correlations existed between PSA and BMI
      (P<0.0001) and triglyceride level (P=0.01). No relationship could be found
      between PSA and serum cholesterol (P=0.711) or high-density lipoprotein (HDL; P
      =0.665). In addition, we found that serum PSA levels increased with age and
      decreased with BMI. Our study demonstrates that age, BMI and triglyceride levels
      influence the PSA level in men <50 years of age.

PMID- 21170077
TI  - The role of C-type natriuretic peptide in rat testes during spermatogenesis.
AB  - C-type natriuretic peptide (CNP) is a 22-amino acid peptide and act as a local
      paracrine or autocrine regulator. There is growing evidence that CNP is involved
      in male reproductive processes. To investigate the role of CNP during
      spermatogenesis, we measured the mRNA expression of CNP and its specific membrane
      bound natriuretic peptide receptor-B (NPR-B) using real-time RT-PCR in the testes
      of normal rats on different postnatal days. After that spermatogenesis
      dysfunction model induced by ornidazole was established with the aim to study the
      correlation of CNP with spermatogenic dysfunction. Then, Sertoli cells from 18-
      to 22-day-old healthy male rats were cultured in the presence of different CNP
      concentrations (1*10(-6), 1*10(-7) and 1*10(-8) mol l(-1)), and the mRNA
      expression levels of androgen-binding protein, inhibin B and transferrin were
      examined at 0 min, 30 min, 1 h, 2 h, 4 h, 8 h, 12 h, 24 h and 48 h. During the
      postnatal development of rat testes, the highest mRNA expression levels of CNP
      and NPR-B were found at postnatal D(0), and the levels then declined gradually,
      with a second CNP peak at postnatal D(35). In the ornidazole-induced infertile
      rat testes, CNP gene expression was lower than in the uninduced rats (P<0.05),
      while NPR-B gene expression was greater (P<0.05). In cultured Sertoli cells,
      supplementation with CNP stimulated the gene expression of androgen-binding
      protein/inhibin B/transferrin, particularly at 12 h, and 1*10(-7) mol l(-1) CNP
      had the highest upregulation effect. The gene expression levels of CNP/NPR-B in
      rat testes at different postnatal stages and in infertile rat testes indicated
      that CNP may participate in the physiology and/or pathology related to
      spermatogenesis. Moreover, CNP regulated endocrine function in Sertoli cells.
      Taken together, these results showed that CNP is closely tied to spermatogenesis.

PMID- 21170078
TI  - Three important components in the regeneration of the cavernous nerve: brain
      derived neurotrophic factor, vascular endothelial growth factor and the JAK/STAT
      signaling pathway.
AB  - Retroperitoneal operations, such as radical prostatectomy, often damage the
      cavernous nerve, resulting in a high incidence of erectile dysfunction. Although
      improved nerve-sparing techniques have reduced the incidence of nerve injury, and
      the administration of phosphodiesterase type 5 inhibitors has revolutionized the
      treatment of erectile dysfunction, this problem remains a considerable challenge.
      In recent years, scientists have focused on brain-derived neurotrophic factor and
      vascular endothelial growth factor in the treatment of cavernous nerve injury in
      rat models. Results showed that both compounds were capable of enhancing the
      regeneration of the cavernous nerve and that activation of the Janus kinase
      (JAK)/signal transducer and activator of transcription (STAT) pathway played a
      major role in the process.

PMID- 21170079
TI  - Expression of multiple glutamate transporter splice variants in the rodent
      testis.
AB  - Glutamate is a regulated molecule in the mammalian testis. Extracellular
      regulation of glutamate in the body is determined largely by the expression of
      plasmalemmal glutamate transporters. We have examined by PCR, western blotting
      and immunocytochemistry the expression of a panel of sodium-dependent
      plasmalemmal glutamate transporters in the rat testis. Proteins examined
      included: glutamate aspartate transporter (GLAST), glutamate transporter 1
      (GLT1), excitatory amino acid carrier 1 (EAAC1), excitatory amino acid
      transporter 4 (EAAT4) and EAAT5. We demonstrate that many of the glutamate
      transporters in the testis are alternately spliced. GLAST is present as exon-3-
      and exon-9-skipping forms. GLT1 was similarly present as the alternately spliced
      forms GLT1b and GLT1c, whereas the abundant brain form (GLT1a) was detectable
      only at the mRNA level. EAAT5 was also strongly expressed, whereas EAAC1 and
      EAAT4 were absent. These patterns of expression were compared with the patterns
      of endogenous glutamate localization and with patterns of d-aspartate
      accumulation, as assessed by immunocytochemistry. The presence of multiple
      glutamate transporters in the testis, including unusually spliced forms, suggests
      that glutamate homeostasis may be critical in this organ. The apparent presence
      of many of these transporters in the testis and sperm may indicate a need for
      glutamate transport by such cells.

PMID- 21170081
TI  - Erasing fear memories - key receptor and essential timeframe discovered.

PMID- 21170080
TI  - Effects of formoterol-budesonide on airway remodeling in patients with moderate
      asthma.
AB  - AIM: To evaluate the effect of inhaled formoterol-budesonide on airway remodeling
      in adult patients with moderate asthma. METHODS: Thirty asthmatic patients and
      thirty control subjects were enrolled. Asthmatic subjects used inhaled Symbicort
      4.5/160 MUg twice daily for one year. The effect of formoterol-budesonide on
      airway remodeling was assessed with comparing high-resolution computer tomography
      (HRCT) images of asthmatic patients and controls, as well as expression levels of
      cytokines and growth factors, inflammatory cell count in induced sputum, and
      airway hyper-responsiveness. RESULTS: The differences in age and gender between
      the two groups were not significant. However, differences in FVC %pred, FEV(1)
      %pred, and PC(20) between the two groups were significant. After treatment with
      formoterol-budesonide, the asthma patients' symptoms were relieved, and their
      lung function was improved. The WT and WA% of HRCT images in patients with asthma
      was increased, whereas treatment with formoterol-budesonide caused these values
      to decrease. The expression of MMP-9, TIMP-1, and TGF-beta(1) in induced sputum
      samples increased in patients with asthma and decreased dramatically after
      treatment with formoterol-budesonide. The WT and WA% are correlated with the
      expression levels of cytokines and growth factors, inflammatory cell count in
      induced sputum, and airway hyper-responsiveness, while these same values are
      correlated negatively with FEV(1)/FVC and FEV(1)%. CONCLUSION: Formoterol
      budesonide might interfere in chronic inflammation and airway remodeling in
      asthmatic patients. HRCT can be used to effectively evaluate airway remodeling in
      asthmatic patients.

PMID- 21170082
TI  - Mixed micelles loaded with silybin-polyene phosphatidylcholine complex improve
      drug solubility.
AB  - AIM: To prepare a novel formulation of phosphatidylcholine (PC)-bile salts (BS)
      mixed micelles (MMs) loaded with silybin (SLB)-PC complex for parenteral
      applications. METHODS: SLB-PC-BS-MMs were prepared using the co-precipitation
      method. Differential scanning calorimetry (DSC) analysis was used to confirm the
      formation of the complex and several parameters were optimized to obtain a high
      quality formulation. The water-solubility, drug loading, particle size, zeta
      potential, morphology and in vivo properties of the SLB-PC-BS-MMs were
      determined. RESULTS: The solubility of SLB in water was increased from 40.83 +/-
      1.18 MUg/mL to 10.14 +/- 0.36 mg/mL with a high drug loading (DL) of 14.43% +/-
      0.44% under optimized conditions. The SLB-PC-BS-MMs were observed by transmission
      electron microscopy (TEM) and scanning electron microscopy (SEM) and showed
      spherical shapes. The particle size and zeta potential, as measured by photon
      correlation spectroscopy (PCS), were about 30 +/- 4.8 nm and -39 +/- 5.0 mV,
      respectively. In vivo studies showed that incorporation of the SLB-PC complex
      into PC-BS-MMs led to a prolonged circulation time of the drug. CONCLUSION: This
      novel formulation appears to be a good candidate for drug substances that exhibit
      poor solubility for parenteral administration.

PMID- 21170084
TI  - BMI-1 suppresses contact inhibition and stabilizes YAP in Ewing sarcoma.
AB  - The polycomb group family protein BMI-1 is overexpressed by and functions as an
      oncogene in many different human cancers. We have previously shown that BMI-1
      promotes the tumorigenicity of Ewing sarcoma family tumors (ESFTs) and that this
      is mediated independently of CDKN2A repression. In this study, we have discovered
      that high levels of BMI-1 confer resistance to contact inhibition in ESFT cells.
      Using stable retroviral transduction, we evaluated the consequences of BMI-1
      knockdown on the growth of CDKN2A wild-type and mutant ESFT cells in subconfluent
      and confluent conditions. Although knockdown of BMI-1 had no effect on
      proliferation in low-density cultures, at high cell densities it resulted in cell
      cycle arrest and death. The normal cell contact inhibition response is mediated,
      in large part, by the recently described Hippo pathway which functions to inhibit
      cell proliferation and promote cell death by inactivating the Yes-Associated
      Protein (YAP). Significantly, we found that YAP levels, activity and expression
      did not diminish in confluent ESFT cells that expressed high levels of BMI-1. In
      contrast, YAP expression and nuclear localization were reduced in confluent BMI-1
      knockdown cells suggesting that silencing of BMI-1 restored contact inhibition by
      restoring normal activation of the Hippo-YAP growth-suppressor pathway.
      Importantly, knockdown of YAP in ESFT cells resulted in profound inhibition of
      cell proliferation and anchorage-independent colony formation suggesting that
      stabilization and continued expression of YAP is critical for ESFT growth and
      tumorigenicity. Together, these studies reveal a previously unrecognized link
      between BMI-1, contact inhibition and the Hippo-YAP pathway and suggest that
      resistance to contact inhibition in BMI-1 overexpressing cancer cells may be in
      part a result of Hippo inhibition and aberrant stabilization of YAP.

PMID- 21170085
TI  - Cyclin-dependent kinase 1 expression is inhibited by p16(INK4a) at the post
      transcriptional level through the microRNA pathway.
AB  - The p16(INK4a) protein regulates cell cycle progression mainly by inhibiting the
      activity of G1-phase cyclin-dependent kinases (CDKs) 4 and 6, the subsequent
      retinoblastoma protein (pRb) phosphorylation and E2F transcription factor
      release. The p16(INK4a) protein can also repress the activity of other
      transcription factors, such as c-myc, nuclear factor-kappaB and c-Jun/AP1. Here,
      we report that, in two p16(-/-), pRb(WT) and p53(WT) cell lines (MCF7 and U87),
      p16(INK4a) overexpression induces a dramatic decrease in CDK1 protein expression.
      In response to p16(INK4a), the decreased rate of CDK1 protein synthesis, its
      unchanged protein half-life, unreduced CDK1 mRNA steady-state levels and mRNA
      half-life allow us to hypothesize that p16(INK4a) could regulate CDK1 expression
      at the post-transcriptional level. This CDK1 downregulation is mediated by the 3'
      untranslated region (3'UTR) of CDK1 mRNA as shown by translational inhibition in
      luciferase assays and is associated with a modified expression balance of
      microRNAs (miRNAs) that potentially regulate CDK1, analyzed by TaqMan Human
      microRNA Array. The p16(INK4a)-induced expression of two miRNAs (miR-410 and miR
      650 chosen as an example) in MCF7 cells is confirmed by individual reverse
      transcription-qPCR. Furthermore, we show the interaction of miR-410 or miR-650
      with CDK1-3'UTR by luciferase assays. Endogenous CDK1 expression decreases upon
      both miRNA overexpression and increases with their simultaneous inhibition. The
      induction of miR-410, but not miR-650 could be related to the pRb/E2F pathway.
      These results demonstrate the post-transcriptional inhibition of CDK1 by
      p16(INK4a). We suggest that p16(INK4a) may regulate gene expression by modifying
      the functional equilibrium of transcription factors and consequently the
      expression balance of miRNAs.

PMID- 21170086
TI  - Genome-wide shRNA screen reveals increased mitochondrial dependence upon mTORC2
      addiction.
AB  - Release from growth factor dependence and acquisition of signalling pathway
      addiction are critical steps in oncogenesis. To identify genes required on
      mammalian target of rapamycin (mTOR) addiction, we performed a genome-wide short
      hairpin RNA screen on a v-H-ras-transformed Pten-deficient cell line that
      displayed two alternative growth modes, interleukin (IL)-3-independent/mTOR
      addicted proliferation (transformed growth mode) and IL-3-dependent/mTOR-non
      addicted proliferation (normal growth mode). We screened for genes required only
      in the absence of IL-3 and thus specifically for the transformed growth mode. The
      top 800 hits from this conditional lethal screen were analyzed in silico and 235
      hits were subsequently rescreened in two additional Pten-deficient cell lines to
      generate a core set of 47 genes. Hits included genes encoding mTOR and the mTOR
      complex 2 (mTORC2) component rictor and several genes encoding mitochondrial
      functions including components of the respiratory chain, adenosine triphosphate
      synthase, the mitochondrial ribosome and mitochondrial fission factor. Small
      interfering RNA knockdown against a sizeable fraction of these genes triggered
      apoptosis in human cancer cell lines but not in normal fibroblasts. We conclude
      that mTORC2-addicted cells require mitochondrial functions that may be novel drug
      targets in human cancer.

PMID- 21170088
TI  - ADAM17 (TACE) regulates TGFbeta signaling through the cleavage of vasorin.
AB  - The activity of a variety of extracellular signaling factors is tightly regulated
      by proteins containing A Disintegrin And a Metalloprotease domain (ADAM)
      metalloproteases through limited proteolysis. Thus, the identification of ADAM
      substrates may unveil novel components and mechanisms of cell signaling pathways.
      We report the identification of the transmembrane protein vasorin (VASN), a
      transforming growth factor-beta (TGFbeta) trap, as a substrate of ADAM17. The
      metalloprotease efficiently generates a soluble fragment encompassing the
      extracellular domain of VASN. Despite the importance of TGFbeta in normal
      development and tumor progression, the regulation of VASN is completely unknown.
      Here, we show that only the soluble form of VASN inhibits TGFbeta and that the
      secretion of VASN is tightly controlled by ADAM17. Hence, inhibition of ADAM17
      leads to the upregulation of TGFbeta signaling. Adding a new level of complexity
      to the function of ADAM17, we finally show that, through the cleavage of VASN,
      the metalloprotease controls TGFbeta-mediated epithelial-to-mesenchymal
      transition.

PMID- 21170083
TI  - NF-kappaB addiction and its role in cancer: 'one size does not fit all'.
AB  - Activation of nuclear factor (NF)-kappaB, one of the most investigated
      transcription factors, has been found to control multiple cellular processes in
      cancer including inflammation, transformation, proliferation, angiogenesis,
      invasion, metastasis, chemoresistance and radioresistance. NF-kappaB is
      constitutively active in most tumor cells, and its suppression inhibits the
      growth of tumor cells, leading to the concept of 'NF-kappaB addiction' in cancer
      cells. Why NF-kappaB is constitutively and persistently active in cancer cells is
      not fully understood, but multiple mechanisms have been delineated including
      agents that activate NF-kappaB (such as viruses, viral proteins, bacteria and
      cytokines), signaling intermediates (such as mutant receptors, overexpression of
      kinases, mutant oncoproteins, degradation of IkappaBalpha, histone deacetylase,
      overexpression of transglutaminase and iNOS) and cross talk between NF-kappaB and
      other transcription factors (such as STAT3, HIF-1alpha, AP1, SP, p53, PPARgamma,
      beta-catenin, AR, GR and ER). As NF-kappaB is 'pre-active' in cancer cells
      through unrelated mechanisms, classic inhibitors of NF-kappaB (for example,
      bortezomib) are unlikely to mediate their anticancer effects through suppression
      of NF-kappaB. This review discusses multiple mechanisms of NF-kappaB activation
      and their regulation by multitargeted agents in contrast to monotargeted agents,
      thus 'one size does not fit all' cancers.

PMID- 21170087
TI  - Ribosomal protein S27-like and S27 interplay with p53-MDM2 axis as a target, a
      substrate and a regulator.
AB  - Several ribosomal proteins regulate p53 function by modulating MDM2. We recently
      found that RPS27L, a RPS27-like protein, is a direct p53-inducible target. Here
      we showed that RPS27 itself is a p53-repressible target. Furthermore, the N
      terminal region of either RPS27L or RPS27 binds to MDM2 on the central acidic
      domain of MDM2. RPS27L or RPS27 forms an in vivo triplex with MDM2-p53 and
      competes with p53 for MDM2 binding. Similar to p53, RPS27L, but not RPS27, is a
      short-lived protein and a novel MDM2 substrate. Degradation of RPS27L requires
      the RING or acidic domain of MDM2. Ectopic expression of RPS27L or RPS27 inhibits
      MDM-2-mediated p53 ubiquitination and increases p53 levels by extending p53
      protein half-life, whereas siRNA silencing of RPS27L decreases p53 levels by
      shortening p53 half-life, with a corresponding reduction in p53 transcription
      activity. RPS27L is mainly localized in the cytoplasm, but upon p53-activating
      signals, a portion of RPS27L shuttled to the nucleoplasm where it colocalizes
      with MDM2. Both the cytoplasmic and the nuclear p53, induced by ribosomal stress,
      were reduced upon RPS27L silencing. Our study reveals a multilevel interplay
      between RPS27L/S27 and p53-MDM2 axis, with RPS27L functioning as a p53 target, a
      MDM2 substrate and a p53 regulator.

PMID- 21170089
TI  - Na(V)1.5 enhances breast cancer cell invasiveness by increasing NHE1-dependent
      H(+) efflux in caveolae.
AB  - Na(V)1.5 sodium channels enhance the invasiveness of breast cancer cells through
      the acidic-dependent activation of cysteine cathepsins. Here, we showed that the
      Na(+)/H(+) exchanger type 1 (NHE1) was an important regulator of H(+) efflux in
      breast cancer cells MDA-MB-231 and that its activity was increased by Na(V)1.5.
      Na(V)1.5 and NHE1 were colocalized in membrane rafts containing caveolin-1. The
      inhibition of Na(V)1.5 or NHE1 induced a similar reduction in cell invasiveness
      and extracellular matrix degradation; no additive effect was observed when they
      were simultaneously inhibited. Our study suggests that Na(V)1.5 and NHE1 are
      functionally coupled and enhance the invasiveness of cancer cells by increasing
      H(+) efflux.

PMID- 21170090
TI  - Cytotoxic T-lymphocyte antigen 4 haplotype correlates with relapse and survival
      after allogeneic hematopoietic SCT.
AB  - CTLA-4 is a negative regulator of activated T cells and the association of CTLA-4
      polymorphisms with autoimmune diseases and transplant outcome has been reported.
      We evaluated the effect of donor CTLA-4 polymorphisms on outcome after allogeneic
      hematopoietic SCT (HSCT). We analyzed 147 Japanese HLA-matched sibling recipients
      and their donors who had undergone allogeneic HSCT. Genotyping of three single
      nucleotide polymorphisms in CTLA-4 (-318, +49, CT60) was performed using TaqMan
      PCR. According to the international HapMap database, only these three CTLA-4
      haplotypes, classified as C-G-G, C-A-A and T-A-G, are present in the Japanese
      population. In this study, percentage expression of the C-G-G, C-A-A and T-A-G
      haplotypes was 59.5, 30.6 and 9.9%, respectively. Recipients of the C-A-A
      haplotype donor showed a significantly lower risk of relapse (HR: 0.54, 95% CI:
      0.30-0.97, P=0.040) and a trend toward higher OS (HR: 0.61, 95% CI: 0.36-1.0,
      P=0.054) than did recipients of a donor without the C-A-A haplotype. The presence
      or absence of the C-A-A haplotype did not affect GVHD or non-relapse mortality.
      As the presence of the C-A-A haplotype reduced relapse risk and improved survival
      after allogeneic HSCT, this CTLA-4 haplotype may provide useful information for
      donor selection.

PMID- 21170091
TI  - Pharmacokinetics and clinical activity of very low-dose alemtuzumab in
      transplantation for acute leukemia.
AB  - The optimal dose of in vivo-administrated alemtuzumab in the allogeneic
      transplantation setting has not been defined. We report our experience on 37
      patients with high-risk diseases, mainly acute leukemia (AML 23, ALL 10
      patients), who underwent sibling (49%) or unrelated (51%) PBSCT (35 patients),
      and received a total dose of only 10-20 mg Campath-1H as part of the
      conditioning, and post-transplant CYA without MTX. The neutrophil and especially
      the platelet engraftment were rapid. There were only two grade III-IV acute GvHD
      cases, which occurred in unrelated transplants in the Campath-10 cohort. Chronic
      GvHD developed in six cases (17%) and was limited to skin in five of them. After
      a median follow-up of 371 days (59-1191), 70% patients are alive and in CR
      (Karnofsky 100%), and 11 died (TRM n=6, relapse n=5). From the five patients
      relapsed, three were at advanced stage at transplant and four underwent sibling
      HCT with the higher (20 mg) alemtuzumab dose. With the 10 mg alemtuzumab schedule
      (5 mg/day at days -2 and -1) we achieve at day of transplantation low but still
      lymphotoxic alemtuzumab serum concentrations (176 ng/mL), whereas levels declined
      fast thereafter, and at engraftment nearly no Campath antibody remained in the
      patient's serum.

PMID- 21170092
TI  - Tumor incidence in related hematopoietic stem cell donors.
AB  - Late malignancies have been discussed as a potential risk for growth factor
      mobilized donors of hematopoietic stem cells. Little is known about the incidence
      and potential risk factors. This single center retrospective cohort study
      evaluated all HLA-identical sibling pairs with hematopoietic stem cell
      transplantation (HSCT) for a hematological malignancy, treated from 1974 to 2001
      at the University Hospital of Basel. Three hundred eighteen pairs were
      identified, 291 donors (92%) could be contacted. Median observation time was 13.8
      years (range 5-32 years). Sixteen (5%) donors had developed a total of 18 tumors,
      17 recipients a secondary tumor. According to the age- and sex-adapted cancer
      incidence, 3.3 tumors in male and 6.8 in female donors were expected, 3 (relative
      risk (RR): 0.91, 95% confidence interval: 0.19-2.66) and 4 (RR: 0.58, 95%
      confidence interval: 0.16-1.48), respectively, were found in donors between 0 and
      49 years. Between 50 and 69 years, 4.5 tumors in males and 4.8 in females were
      expected, 5 (RR: 1.11, 95% confidence interval: 0.36-2.59) and 6 (RR: 1.23, 95%
      confidence interval: 0.45-2.67), respectively, were observed. Tumors do occur in
      donors of hematopoietic stem cells at least at the rate as expected in a normal
      population; whether incidence exceeds expected rates needs to be determined in
      larger international cohorts.

PMID- 21170093
TI  - BU- vs TBI-based conditioning for adult patients with ALL.
AB  - Evidence suggests an advantage for TBI over BU as a component of conditioning
      regimens for allogeneic hematopoietic cell transplant in patients with ALL. We
      have employed both TBI and BU for conditioning in ALL and reviewed our experience
      to compare outcomes. From July 1989 to June 2008, we identified 86-adult ALL
      patients treated with either a TBI- or BU-based regimen and transplanted with
      either a well-matched sibling or unrelated donor. Data including demographics,
      immunophenotype, disease status and cytogenetic risk were examined by Cox
      proportional hazards analysis. Patients treated with TBI were older (median age
      40 vs 33 years; P=0.018), had a higher-risk cytogenetic profile (P=0.010), were
      more often transplanted using an unrelated donor (P=0.038) and were treated more
      recently (P<0.001). There was a significant improvement in EFS (P=0.046), and a
      trend to improved OS (P=0.08) in patients treated with TBI compared with those
      treated with BU. However, the advantage for TBI could not be confirmed by
      multivariable analysis where only disease status retained statistical
      significance.

PMID- 21170094
TI  - [Management of hepatic artery related complications and its outcome during liver
      transplantation].
AB  - OBJECTIVE: To explore the experience of hepatic arterial reconstruction and
      management of its complications. METHODS: The clinical data of 570 consecutive
      orthotopic liver transplantation patients performed from May 2001 to May 2009 in
      Peking University People's Hospital were analyzed retrospectively in order to
      summarize the key factors of hepatic arterial reconstruction and the experience
      of management of its complications. RESULTS: Arterial complications developed in
      18 (3.1%) of the 570 patients including 11 cases of hepatic artery thrombosis, 5
      cases of hepatic artery stenosis and 2 cases of hepatic artery rupture. Of the 11
      cases with early complication (within 4 weeks), 7 patients died, including 2 due
      to the rupture of hepatic artery and 5 due to acute liver failure and sepsis of
      hepatic artery thrombosis. Of the 7 cases with late complication, 4 patients
      died, including 1 due to graft failure and 3 due to ischemic-type biliary
      complications. CONCLUSION: Good quality of donor artery and proper choice of
      microsurgical anastomosis technique in hepatic artery reconstruction could
      significantly reduce the incidence of its complication. Early detection and
      diagnosis with active early interventional therapy can improve prognosis of the
      patients.

PMID- 21170095
TI  - [Anesthesia for cesarean section in pregnancy complicated with severe scoliosis:
      a case report].
AB  - Scoliosis refers to a complex three-dimensional spine deformity. Onset of
      scoliosis can occur in an infantile, juvenile, adolescent, or adult period.
      Severe scoliosis not only affects the appearance of the patient, but also impairs
      the functions of circulation and respiratory systems. Significant changes of the
      cardiopulmonary function can occur during pregnancy. In this report, general
      anesthesia was needed for emergent cesarean section of the puerperant complicated
      with severe scoliosis. The puerperant had already suffered type II respiratory
      failure preoperatively. There might be managements of difficult airway,
      depression with circulation and respiration of the neonate, and the risk for
      inhibition of the uterine contraction and awareness. Facing the challenges, the
      anesthesiologists must work out a detail anesthesia plan quickly, and make sure
      the safety of the puerperant and the neonate.

PMID- 21170096
TI  - [Genotype, phenotype analysis and follow-up study on patients with
      Duchenne/Becker muscular dystrophy].
AB  - OBJECTIVE: To improve the diagnosis and management of Duchenne/Becker muscular
      dystrophy(DMD/BMD). METHODS: Clinical features of 90 cases of DMD/BMD were
      collected. Genomic DNA was extracted using standard procedures from the
      peripheral blood leukocytes, and multiplex ligation-dependent probe amplification
      (MLPA) was applied to detect DMD gene to identify genetic mutation. For those
      patients whose deletion/duplication mutation was not identified, FKRP gene
      mutation analysis was performed using PCR-DNA direct sequence. All the cases were
      followed up. RESULTS: Among the 90 cases of clinically diagnosed DMD/BMD, exons
      deletion of DMD was detected in 58 cases (64.44%), and exons duplication in 9
      (10.00%). Among the 34 mothers with an affected boy but without previous genetic
      conformation, 17 were confirmed to be carriers with gene deletion/duplication.
      None of the 23 cases, without detected DMD gene deletion/duplication, carried
      FKRP gene mutation. Fourteen children were given short-term intermittent
      prednisone therapy (0.75 mg/kg daily during the first 10 days of each month). The
      course was not long enough and the sample size was too small to conclude any
      benefits or side effects. Prenatal diagnosis was provided for one mother in her
      next pregnancy detecting a female carrier fetus. CONCLUSION: DMD gene deletions
      mainly occurs between exons 45 and 54, while duplications mostly at 5'-terminus.
      Identification of the characteristics and types of gene mutation may facilitate
      the recognition and prognosis prediction of DMD/BMD. MLPA is a non-complex and
      quick diagnostic tool for DMD/BMD and its carriers, and also helpful in genetic
      counseling.

PMID- 21170097
TI  - [Hypertension and peripheral arterial diseases].
AB  - OBJECTIVE: To explore the relationship between different blood pressure levels
      and peripheral arterial disease (PAD) assessed by ankle-brachial index (ABI).
      METHODS: Data including ABI,blood pressure, health history, medication use, blood
      biochemistry and physical examinations derived from 15 817 subjects from 9 areas
      throughout China were analyzed. Univariate and multivariate adjusted Logistic
      regression analyses were used for the data analyses. RESULTS: Blood pressure
      levels were classified into 5 levels as normal blood pressure, high normal blood
      pressure, primary hypertension, secondary hypertension and the third grade of
      hypertension. With the increasing of blood pressure levels, the risk of PAD
      gradually increased (Ptrend<0.05). In comparison with normal blood pressure
      group, the ORs of PAD for the other groups were 1.10 (95%CI: 0.93-1.29), 1.17
      (95% CI: 0.97-1.40), 1.91 (95% CI: 1.55-2.37), and 2.64 (95% CI: 1.99-3.49),
      respectively. After adjusting for gender(only for total population), age,
      urban/rural, smoke, obesity/overweight, the history of hypercholesterolemia and
      diabetes, the ORs were 1.11 (95%CI: 0.94-1.32), 1.13 (95% CI: 0.93-1.38),
      1.85(95% CI: 1.47-2.33), and 2.66 (95% CI: 1.98-3.57) (Ptrend<0.05). CONCLUSION:
      PAD risk increases in proportion with the increasing blood pressure level.

PMID- 21170098
TI  - [Clinical significance of detection of plasma and urine IgG4 in idiopathic
      membranous nephropathy].
AB  - OBJECTIVE: To investigate the possibility of IgG4/IgG as one of biomarkers to
      reflect disease activity and the relapse of idiopathic membranous nephropathy
      (IMN). METHODS: Plasma and urine samples were obtained from patients with IMN
      (Twenty-four patients had follow-up data), minimal change disease (MCD) and focal
      segmental glomerulosclerosis (FSGS) before immunosuppressive therapy.
      Concentrations of plasma and urine IgG4 and total IgG were detected by sandwich
      ELISA. The ratio of IgG4/IgG was calculated as the concentration of IgG4 divided
      by total IgG. RESULTS: Both plasma and urine IgG4/IgG ratios were significantly
      higher in IMN group compared with MCD or FSGS group (both P<0.05). In IMN, both
      plasma and urine IgG4/IgG ratios in patients with nephritic syndrome were
      significantly higher versus those with subnephrotic proteinuria (P=0.063;
      P<0.05). Both plasma and urine IgG4/IgG ratios were significantly decreased with
      remission (P<0.05) and maintained or even increased with resistance to therapy.
      Patients who relapsed within 2 years had higher urine IgG4/IgG-ratios than those
      who had no relapse (P<0.05), and patients with urine IgG4/IgG-ratios>=9% upon
      renal biopsy had higher relapse tendency (P=0.071). CONCLUSION: Both plasma and
      urine IgG4/IgG ratios might be a promising biomarker to reflect disease activity
      of IMN, and higher urine IgG4/IgG ratios might suggest higher relapse tendency.

PMID- 21170099
TI  - [Usability of the laboratory report and knowledge of lipid-lowering in out
      patients from dyslipidemia-related departments].
AB  - OBJECTIVE: To investigate the usability of laboratory test report from the angle
      of patients and understand to what degree the patients master the knowledge of
      lipid-lowering. METHODS: A total of 508 outpatients, selected from a Grade III-A
      general hospital, were queried by a questionnaire, their medical records and test
      reports were reviewed and their heights and weights were measured. In the study,
      431 of them fulfilled the inclusion criteria and their information about lipid
      lowering treatment and treatment compliance were collected. RESULTS: Of the 508
      subjects, 90.2% (458/508) read the report seriously; however, only 47.4%
      (240/508) took drugs according to the doctor's prescription even if the tests
      were "normal". Of the 431 lipid-lowering therapy related patients, only 26.4%
      (112/431) chose right in their cardiovascular risk classification, and less than
      37.1% (160/431) agreed that "different people had different lipid lowering
      target". Of the 381 patients who needed the lipid-lowering treatment, 71.7%
      (273/381) recognized the need for treatment, but 98.7% (376/381) answered a wrong
      target for treatment; 60.9% (232/381) recognized that the reference values given
      in the laboratory test reports should be the target for treatment. Of the 246
      patients under the lipid-lowering treatment, 35.4% (87/246)had reached their
      treatment goals, and only 52.0% (128/246) had a good compliance. CONCLUSION: Most
      patients read and trusted the laboratory test reports. However, dyslipidemia
      patients scarcely knew their lipid lowering treatment goals and their
      cardiovascular risk levels. The compliance of patients was poor, and the goal
      attainment was low. The laboratory medicine department should find out a simple
      and intuitional way to change the current situation.

PMID- 21170100
TI  - [Neurocognitive performance in the patients with first-episode schizophrenia and
      their independent first-degree relatives: a cross-sectional study].
AB  - OBJECTIVE: To evaluate neurocognitive performance in first-episode schizophrenic
      patients and unaffected first-degree relatives of different patients samples.
      METHODS: A total of 42 patients with first-episode schizophrenia, 24 unaffected
      first-degree relatives and 40 healthy individuals, matched with age, gender and
      years of education, were recruited from both outpatients and inpatients after
      being diagnosed with structured tool (SCID-I/P). Subjects' cognitive performance
      was evaluated by a set of neuropsychological test battery, which assessed four
      cognitive domains including learning and memory, motor skills, speed of
      processing and executive function. RESULTS: Healthy individuals performed better
      than first-episode schizophrenic patients in nearly all cognitive domains
      (ES=0.63-1.54) with exception of inhibition sub-domain. first-degree relatives
      showed moderate impairment in verbal learning (ES=0.62), digital symbol
      (ES=1.05), symbol search (ES=1.18), animal category (ES=0.80) and WCST
      perseverate errors (ES=0.68). Degree of impairment in first-degree relatives was
      less than that in the patients. CONCLUSION: Patients with first-episode
      schizophrenia have global neurocognitive deficits. Independent first-degree
      relatives also have deficits in some neurocognitive domains, with a moderate
      degree between patients and normal controls. Our results indicate that
      neurocognitive performance may be viewed as a biomarker for candidates reflecting
      genetic liability for schizophrenia.

PMID- 21170101
TI  - [Risk factors of melamine-contaminated milk powder related urolithiasis: a
      multicenter nested case-control study].
AB  - OBJECTIVE: To further confirm and clarify the risk factors of melamine associated
      urolithiasis. METHODS: Case control research was performed in 6 centers from 5
      provinces/cities in China. Children less than 36 months old were screened for
      urolithiasis and recruited in the study. The children with urolithiasis were
      included as cases and those without urolithiasis as controls. The children with
      congenital abnormality of urinary tract were excluded. According to the
      case:control ratios of 1:1, we sampled the controls from healthy children
      screened randomly. Due to the complete missing data on factors of
      vomiting/diarrhea/fever in control group of Center 4, we analyzed the data from 6
      centers and 5 centers respectively. The possible influencing factors for
      urolithiasis including melamine concentration, birth type, age, feeding style and
      history of vomiting or diarrhea or fever were analyzed by Logistic analysis.
      RESULTS: There were 1 329 cases and 1 317 controls with a mean age of 18.4
      months. The analysis of data from 6 centers showed the children fed with high
      melamine formula were 6.26 times more likely to have stones (P<0.01) than those
      with non melamine formula. Preterm infants were 2.03 times (P<0.01) more likely
      to have urolithiasis than term infants. The children aged less than 0.5 year, 0.5
      to 1 year, 1 to 2 year, 2 to 2.4 year were 2.78 (P<0.01), 2.61 (P<0.01), 2.09
      (P<0.01), 1.57 (P<0.01), 1.44 (P<0.05) times more likely to have stones than
      those more than 2.5 year. Boys were 1.19 times more likely to have stones than
      girls. Children fed with formula alone were 1.94 times (P<0.01) more likely to
      have stones than those with formula and breast milk. The analysis of data from 5
      centers showed that children fed with high melamine formula were 4.38 times
      (P<0.01) more likely to have stones compared with those with non melamine
      formula. Children aged less than 1 year and 1 to 1.9 year were 2.24 (P<0.01) and
      1.31 (P<0.05) times more likely to have stones than those more than 2 year. The
      children fed with formula alone were 1.67 times (P<0.01) more likely to have
      stones compared to those with formula and breast milk. The children with any two
      symptoms of vomiting, diarrhea and fever were 15.21 times (P<0.05) more likely to
      have urolithiasis. The multiple logistic regression model confirmed that above
      risk factors were independent risk factors for urolithiasis. CONCLUSION: We
      confirm that the children fed with high melamine infant formula, preterm infant,
      boy, children fed with formula alone, and the children with symptoms of vomiting
      or diarrhea or fever are more likely to have urolithiasis. We also found the risk
      for urolithiasis decreased with age.

PMID- 21170102
TI  - [Relationship between craniofacial and airway structure and pediatric obstructive
      sleep apnea and hyponea syndromes: a case-control study].
AB  - OBJECTIVE: The children obstructive sleep apnea and hyponea syndromes has become
      a global research hot spot, but the research of craniofacial features in
      obstructive sleep apnea and hyponea syndromes (OSAHS) children was scarce. To
      evaluate the craniofacial features of obstructive sleep apnea and hyponea
      syndromes children. METHODS: The subjects involved in this study fell into two
      groups: the patient group and the control one. The patients and controls were
      strictly matched by age and sex. Lateral head radiographs and cephalometric
      measurements were obtained and then compared between the two groups. RESULTS: The
      findings demonstrated marked differences in terms of SNB, PG-NB, lower facial
      height, H-C3Me and A&T/P. The SNB angle (75.8+/-4.3) in the patient group was
      smaller than that in the control one (78.7+/-2.6) and the P value was 0.035; the
      PG/NB value in the patient group (1.3+/-0.8) mm was higher than that in the
      control one (0.6+/-0.6) mm and the P value was 0.02. The anterior face height was
      (65.1+/-5.9) mm in the patient group (P=0.04), while the anterior face height in
      the control group was (61.5+/-3.2) mm. The position of hyoid was lower in the
      patient group(5.3+/-3.7) mm, compared with the control one (2.6+/-2.6) mm, and
      the P value was 0.03. Furthermore, the patients of OSAHS had more swelled
      adenoids and tonsils than the controls. CONCLUSION: The patient group differed
      from the control group in the length of mandible, lower facial height, position
      of hyoid and the chin, and the size of the adenoids and tonsils.

PMID- 21170103
TI  - [Risk factors associated with failure from endoscopic therapy in acute non
      variceal upper gastrointestinal bleeding].
AB  - OBJECTIVE: To determine risk factors associated with failure of endoscopic
      therapy in acute non-variceal upper gastrointestinal bleeding (ANVUGIB ).
      METHODS: This was a retrospective cohort study of 223 patients admitted to Peking
      University Third Hospital between 1 January 2005 and 31 December 2009, with acute
      non-variceal upper gastrointestinal bleeding. Data on clinical presentation,
      laboratory test, endoscopic findings, and treatment outcomes were collected. Risk
      factors for treatment failure were identified using multivariable Logistic
      regression with backward selection. RESULTS: Therapeutic failure rate was
      19.3%(43/223). In univariate analysis, the two groups had significant difference
      in age, history of gastrointestinal bleeding, ASA, shock, haemoglobin level, Hct,
      PLT, time of endoscopic treatment, gastric ulcer, duodenal ulcer, lesion size and
      active spurting of blood. Multivariate Logistic regression analysis revealed that
      shock [odds ratio (OR) 3.058, 95% confidence interval (CI) 1.295-7.221], history
      of gastrointestinal bleeding (OR 2.809, 95% CI 1.207-6.539), PLT>100*109/L (OR
      0.067, 95% CI 0.009-0.497), active spurting of blood (OR 10.390, 95% CI 2.835
      38.080) and lesion size>=2.0 cm (OR 7.111, 95% CI 1.628-31.069) were risk factors
      associated with failure of endoscopic therapy. The number of comorbidities>1 (OR
      9.580,95%CI 1.383-66.390) and active spurting of blood (OR 9.971, 95% CI 1.820
      54.621) were factors related with need for surgical intervention or death.
      CONCLUSION: Patients with shock, history of gastrointestinal bleeding,
      PLT<100*109/L, active spurting of blood and large lesion size, have high risks
      for continued bleeding or rebleeding after endoscopic treatment. These patients
      may be more likely to benefit from aggressive post-hemostasis care.

PMID- 21170104
TI  - [Prognostic factors for patients with pulmonary thromboembolism after orthopaedic
      surgery].
AB  - OBJECTIVE: To investigate the changes of serum enzymes and their prognostic value
      in patients with pulmonary thromboembolism after orthopaedic surgery. METHODS:
      Clinical data of 134 cases of confirmed pulmonary thromboembolism after
      orthopaedic surgery from 1997 to 2010 were reviewed.The 134 cases were divided
      into dead group (n=28) and survival group (n=106). The clinical presentation,
      electrocardiogram, arterial oxygen pressure (PaO2), chest X-ray,
      echocardiography,and serum enzymes including alanine transaminase (ALT),
      aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (gamma-GT),
      lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme
      (CK-MB) were analyzed. And multivariable Logistic regression was conducted to
      identify the risk factors of in-hospital death. RESULTS: The average age of dead
      patients was higher than that of survival patients (P=0.043), while the P(O2) of
      dead patients was much lower than that of survival patients (P=0.035). The
      percentage of syncope, hypotension, right bundle-branch block and SIQIIITIII,
      pulmonary hypertension and right ventricular dysfunction in dead patients were
      higher than those in survival patients (P=0.009, P=0.041, P=0.018, P=0.030,
      P=0.042 and P=0.038), respectively. There were significant differences of
      elevated serum ALT, LDH and CK-MB levels between dead patients and survival
      patients (P=0.042, P=0.035 and P=0.017). Logistic regression indicated that the
      risk factors for death of patients with PTE after orthopaedic surgery were age
      (OR, 1.182; 95% CI, 1.010-1.383; P=0.036), hypoxemia (OR, 1.128; 95% CI, 1.018
      1.249; P=0.022), hypotension (OR, 3.346; 95% CI, 1.116-10.031; P=0.031), right
      ventricular dysfunction (OR, 4.083; 95% CI, 1.040- 16.035; P=0.044) and elevated
      serum CK-MB levels (OR, 3.466; 95% CI, 1.054-11.400; P=0.041). CONCLUSION: The
      incidence rate of elevated serum ALT, LDH and CK-MB levels in patients who died
      of pulmonary thromboembolism after orthopaedic surgery was higher than that of
      survival patients; Age, hypoxemia, hypotension and right ventricular dysfunction
      were independent risk factors of in-hospital death; The CK-MB might be a useful
      biomarker for risk stratification of acute PTE.

PMID- 21170105
TI  - [Long-term efficacy of radiofrequency ablation in 446 patients with
      hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate the efficacy of radiofrequency ablation (RFA) for
      hepatocellular carcinoma (HCC) according to standardized treatment strategy and
      individualized protocol. METHODS: A total of 468 patients of HCC underwent
      ultrasound/Contrast-enhanced ultrasound guided RF ablation in our department
      according to individualized protocol for large tumors, hypervascular tumors and
      tumors located adjacent to important structures in our study, of which 22 HCCs
      having undergone palliative RF ablation were excluded because of huge size,
      diffusive multiple tumors or adjacent structures invasion. The remaining 446 HCCs
      (680 sessions) were included and followed-up regularly to assess treatment
      efficiency. Of the 446 patients, 367 were male and 79 were female. 828 lesions
      underwent RFA. The mean size of tumors was (3.6+/-1.4)cm. Regular follow-up was
      conducted for 3-119 months. In this study, long-term outcome of various
      refractory tumors were also investigated. RESULTS: The overall ablation success
      rate was 97%(803/828) 1 month after RFA. The recurrent rate was 7.2% (60/828).
      Base on Kaplan-Meier method, the 1-, 3- and 5-year overall survival rates after
      RF ablation were 85.3%, 61.3% and 47.0%, respectively. The ablation success rate
      of tumors larger than 3.5 cm was 90.8% (275/303). The 5-year survival rates of
      patients who had HCC for 3.1-5 cm and >5 cm were 45.1% and 35.9%, respectively.
      In this study, there were 40.3% (334/828) tumors located adjacent to important
      structures. The ablation success rates of these tumors located adjacent to
      gallbladder, diaphragm, bowel and major vessels were 93.5% (58/62), 92.5%
      (123/133), 92.4% (61/66) and 93.2% (68/73), respectively. The incidence of major
      complications was 3.1% (21/680), which included 5 intraperitoneal hemorrhages, 4
      biliary injuries, 2 hemopleural effusions, 3 bowel perforations and 7 needle
      tract seedings. Treatment-related death occurred in 1 case of bowel perforation.
      CONCLUSION: In RF ablation of refractory HCC, application of standardized
      treatment strategy and individualized protocol plays important roles in improving
      ablation success rate and minimizing potential complications. It could extend the
      indications of RF ablation for HCC in China.

PMID- 21170106
TI  - [Multicenter randomized, double-blind, placebo-controlled trial of prostaglandin
      E1 cream for female sexual arousal disorder].
AB  - OBJECTIVE: To investigate the efficacy and safety of alprostadil cream in
      management of female sexual arouse disorder (FSAD), and its appropriate dose for
      clinical prescription. METHODS: The volunteers were assigned randomly to four
      groups which received alprostadil cream in different dosage (500 MUg, 700 MUg and
      900 MUg) or placebo cream, respectively. The cream was applied to the clitoris
      and G-spot before coitus. The efficacy was assessed by comparing the satisfactory
      rate of sexual arousal, the score of female sexual function index (FSFI) and
      female sex disorder scale (FSDS) and the general appraised question (GAQ) before
      and after the treatment. The safety was evaluated by the adverse effects that
      appeared including symptoms, physical and biochemical examination. RESULTS:
      Totally, 400 women enrolled in this study with 374 assigned to the group for
      efficacy evaluation and 387 cases to the group for safety analysis. No
      significant difference was found among the four groups in the demographic
      characters and sexual baseline. The increase of satisfactory percentage of sexual
      arousal in the four groups (placebo, 500 MUg, 700 MUg and 900 MUg) was 22.63%,
      36.67%, 34.01%, and 44.29%, respectively (P<0.05), and the increase was
      statistically higher in the 900 MUg group than in the placebo group (P<0.0167).
      The elevated FSFI score above the baseline in the treatment groups (900 MUg
      22.89, 700 MUg 21.69, and 500 MUg 20.71) were higher than that in the placebo
      group (14.68, P<0.05), while the reduced FSDS score below the baseline (900 MUg
      25.97, 700 MUg 21.98, and 500 MUg 20.27) were higher than that of the placebo
      (17.60, P<0.05). No significant difference was found in the four groups in GAQ
      (P=0.054). The main common adverse effect was topical stimulation. No adverse
      effect was reported in physical and biochemical examination, electrocardiogram
      (ECG) or Thinprep cytologic test (TCT). CONCLUSION: Alprostadil cream can treat
      female sexual arousal disorder effectively with the maximum effect at the dose of
      900 MUg and without significant adverse effect except for mild topical
      stimulation.

PMID- 21170107
TI  - [Effect of remifentanil on propofol pharmacokinetics with target controlled
      infusion in elderly patients].
AB  - OBJECTIVE: To investigate the effects of remifentanil administered by target
      controlled infusion (TCI) with different plasma concentration and time on
      pharmacokinetics of propofol in elderly patients. METHODS: Thirty-two ASA I-II
      patients (65-82 years old) undergoing elective lower abdominal operations were
      divided into 4 groups randomly: TCI propofol combined with epidural block (group
      A, n=8); TCI remifentanil with plasma concentration 4 MUg/L and propofol (group
      B, n=8); TCI remifentanil with plasma concentration 7 MUg/L and propofol (group
      C, n=8); and TCI propofol and remifentanil (plasma concentration 4 MUg/L) with
      infusion time longer than 4 hours (group D, n=8). Propofol was infused by target
      controlled infusion with plasma concentration 3 mg/L in the 4 groups. bispetral
      index (BIS), heart rate (HR), blood pressure (BP) were recorded during operation.
      Blood samples were collection from radial arterial catheter. Samples of 2 mL of
      arterial blood were taken at 0, 1, 3, 5, 10, 15, 30 min and then every 30 min
      after the start of the infusion of propofol, and at 0, 2, 4, 6, 8, 10, 15, 30,
      45, 60, 120, 240, 360, 480, 720, 1440 min after the termination of the infusion
      of propofol. Propofol concentrations in blood were measured by reversed-phase
      high-performance liquid chromatography (HPLC). The pharmacokinetics analyses were
      performed using the nonlinear mixed-effects model approach implemented in NONMEM
      computer program. After obtaining the best NONMEM model with covariates, the
      influence of coadministered remifentanil on the model was examined. RESULTS: In
      all the patients, the depth of anesthesia was enough (BIS value=40-60), and the
      circulatory system function was stable during operation. The final model of
      propofol pharmacokinetics in the three groups (A+B, A+C, and A+D groups) was best
      described by a three-compartment mammillary model. The values of objective
      function (OFV) were -810.1, -714.4, and -896.4. Addition of remifentanil
      covariate effects to the final model resulted in no improvement in the objective
      function. CONCLUSION: target-controlled infusion of propofol combined with
      different plasma concentration of remifentanil or remifentanil infusing more than
      4 hours had no effect on pharmacokinetics of propofol in elderly patients.

PMID- 21170108
TI  - [Comparison of lamivudine or interferon monotherapy and sequential therapy in
      chronic hepatitis B: a random controlled trial].
AB  - OBJECTIVE: To compare the efficacy and safety of lamivudine or interferon
      monotherapy and sequential therapy in HBeAg positive chronic hepatitis B
      patients. METHODS: A total of 225 patients with HBeAg positive chronic hepatitis
      B were randomized into 3 groups: sequential group (group A, 83 patients),
      lamivudine group (group B, 89 patients) and interferon group (group C, 53
      patients). Group A was administrated with lamivudine 100 mg/d for 32 week, and 5
      million units of interferon alpha 2b injected subcutaneously every other day
      lasting for 24 week were added since week 25. Group B was administrated with
      lamivudine 100 mg/d for 48 week. Group B was injected with 5 million units of
      interferon alpha 2b subcutaneously every other day for 24 week. All subjects were
      followed up for 24 week. Serum HBV DNAs were measured quantitatively by PCR. HBV
      mutations were analyzed by PCR-RFLP. RESULTS: For groups A, B and C, baseline HBV
      DNAs were 7.8+/-1.0, 7.9+/-1.1 and 8.0+/-0.9 log10 copies/mL, respectively,
      P>0.05. Baseline ALTs were 167.5 (99.0, 267.8), 134.0 (101.0,275.0) and 131.0
      (99.0, 192.8)U/L, respectively, P>0.05. At the end of the treatment, HBV DNA
      decrease rates for groups A, B and C were 78.2%, 87.8% and 78.4% (P>0.05),
      respectively. At the end of the follow-up, HBV DNA decrease rates for groups A, B
      and C were 54.4%, 63.6% and 66.7% (P>0.05), respectively. At the end of the
      treatment, group B (83.5%, P<0.05) achieved the highest response rate and group C
      achieved the lowest (39.6%, P<0.05). At the end of the follow-up, the response
      rates for groups A, B and C were 36.2%, 54.4% and 42.1% (P>0.05), respectively.
      YMDD motif mutation rate in group A was lower than that of group B (10.5% vs
      26.9%, P<0.05) at the end of the treatment. CONCLUSION: Sequential therapy
      decreased hepatitis B virus mutation. But no efficacy advantages were found in
      sequential therapy than in lamivudine or interferon monotherapy.

PMID- 21170109
TI  - [Sucrose Gel for the treatment of bacterial vaginosis: a phase II clinical
      trial].
AB  - OBJECTIVE: To evaluate the effective dose and safety of S-Gel in the treatment of
      bacterial vaginosis. METHODS: Clinical research method of multi- center, randomly
      double-blind, and dose group parallel comparison was adopted. In the study, 96
      bacterial vaginosis patients were randomized into three groups: Group A, S-Gel
      5.0 g, 32 patients; Group B, S-Gel 7.5 g, 32 patients; Group C, placebo, 32
      patients. The patients were treated with different methods. Safety and efficacy
      were analyzed 3 to 4 days and 8 days after the treatment, respectively. RESULTS:
      The efficacy of comprehensive clinical treatment showed that: 8 days after the
      treatment, the cure rates of group A (5.0 g), group B (7.5 g), and group C
      (placebo) were 84.38%, 86.67%, and 3.13% respectively. No difference of statistic
      significance was found in groups A and B, difference of statistical significance
      was found in group A and group C, group B and group C respectively (P<0.001).
      CONCLUSION: As compared with placebo, S-Gel 7.5 g and 5.0 g bid (in the morning
      and evening) could obviously improve the clinical efficacy index and laboratory
      index of bacterial vaginosis. Other effects included the release of clinical
      symptoms, and the recovery of the normal micro-environment in the vagina. No
      significant difference was found in the cure rates of the two dose groups.

PMID- 21170110
TI  - [Evaluation of the use of ultrasonic hand piece and micro-invasive tips in
      children's dental caries therapy].
AB  - OBJECTIVE: To assess the effect and efficacy of an ultrasonic hand piece and
      micro-invasive tips in removal of carious lesion, as well as the pediatric
      patients' feedback of this device in comparison to the conventional one. METHODS:
      Seventy-two pediatric patients aged 3 to 12 were recruited in the study. Each
      patient had at least two carious lesions bilaterally in the same arch, one tooth
      was assigned to be treated with ultrasonic hand piece and micro -invasive tips
      (MIT) while the contra lateral side was treated with conventional hand piece. The
      effect and efficacy of MIT was determined by the appearance of the color and
      texture of the teeth, the patient's reaction during the treatment, and the pain
      scale level. Postoperative sensitivity, restoration and plaque score were also
      recorded in the follow-up visit after six months. The result was evaluated with
      SPSS 14.0 statistic software Wilcoxon Signed Ranks Test and t-test. RESULTS: The
      average treatment time of the experimental group was 4 minutes; and that of the
      control group 3 minutes and 34 seconds (P<0.05), which was a clinically
      significant difference. Both methods were effective in removing carious lesion.
      In comparison to the patient anxiety and cooperation, the scores of the
      experimental group were fewer than those of the control group, which was also a
      clinically significant difference. In the experimental group, 89.2% of the
      patients felt comfortable or slightly uncomfortable, while 73.1% of the patients
      did in the control group. In the 6-month follow-up study, 1 treated tooth from
      the experimental group had sensitivity, while 4 treated teeth from the control
      group had sensitivity. And 88.2% of the pediatric patients expressed that they
      were more willing to be treated with ultrasonic hand piece and micro-invasive
      tips. CONCLUSION: Ultrasonic hand piece and micro-invasive tips is equally
      effective in removing carious lesion like the conventional hand piece. SONICFlex
      has reduced noise level, and made the operation more precise with less pulp
      sensitivity, and thus is more acceptable to pediatric patients.

PMID- 21170111
TI  - [A meta-analysis of aprepitant for prevention of chemotherapy-induced nausea and
      vomiting].
AB  - OBJECTIVE: To assess the efficacy and safety of aprepitant for the prevention of
      chemotherapy-induced nausea and vomiting (CINV) after moderately or highly
      emetogenic chemotherapy. METHODS: Studies were identified by searching PubMed
      (1980 to March, 2010), EMbase (1980 to March, 2010), Cochrane Libraries (Issue 2,
      2010), CNKI (1980 to March, 2010), CBMdisc (1980 to March, 2010), and WanFang
      Data (1982 to March, 2010). Randomized controlled trials of aprepitant for the
      prevention of CINV were included. The quality of included studies was assessed
      and meta-analysis was performed for the results of homogeneous studies by RevMan
      5.0.23 software. RESULTS: Ten studies involving 4 376 oncology patients were
      included. They were all high quality studies, with Jadad scores more than 5. The
      results of meta-analysis were as follows: (1) Acute CINV: The overall complete
      response rate was improved by 14.21% when aprepitant was combined with
      ondansetron and dexamethasone (83.33% vs 72.96%; P<0.001). Subgroup analysis
      showed the patients receiving AC (anthracycline/cyclophosphamide) regimen
      benefited less than the patients receiving cisplatin chemotherapy. The rate of no
      significant nausea was only improved by 3.92% (P=0.04). (2) Delayed CINV:
      Compared with ondansetron, aprepitant could improve vomiting by 14.98% (P=0.004).
      When aprepitant was added with dexamethasone, the response rate of vomiting and
      nausea was improved by 37.72% (P<0.001) and 11.24% (P=0.008) respectively. (3)
      Adverse reactions: The incidence of fatigue/asthenia was higher in the aprepitant
      regimen (P=0.001), while the incidence of constipation was lower (P=0.002).
      CONCLUSION: Aprepitant can improve the control of vomiting, but has slight effect
      on nausea. Patients receiving AC regimen benefit less than patients receiving
      cisplatin chemotherapy. In view of its high cost, pharmacoeconomics researches of
      aprepitant should be considered.

PMID- 21170112
TI  - [Small hepatocellular carcinoma in patients with hepatitis B-induced cirrhosis: a
      comparison between MRI and MDCT].
AB  - OBJECTIVE: To compare efficacy of plain and contrast enhancement MRI (1.5T or 3T)
      and dynamic contrast enhanced multidetector CT (MDCT, 16- or 64 -slice) for the
      detection of small hepatocellular carcinoma (HCC) in patients with hepatitis B
      induced cirrhosis. METHODS: A total of 21 patients (18 men, 3 women; age range,
      44-74 years) with 22 small HCC and liver cirrhosis were enrolled, all having
      undergone MDCT and MRI within one month. The diagnosis of small HCC was
      established at surgical resection (n=4), percutaneous biopsy (n=1), with positive
      tumor staining at intervention or from combined clinical data, typical imaging
      features and follow-up for a period of at least one year. Triple-phase or dual
      phase dynamic contrast enhancement was performed on a 16- or 64-slice MDCT. MRI
      sequences included transverse T1-weighed images acquired as fast spoiled gradient
      (FSPGR) in-phase and out-of-phase dual-echo, transverse T2-weighed images with
      respiratory triggering acquired as fat-suppressed fast spin echo (FSE) or fast
      recovery fast spin echo (FRFSE), and breath-hold coronal T2-weighed images
      acquired as single shot fast spin echo (SSFSE) or fast imaging employing steady
      state acquisition (FIESTA). CT and MRI observers independently analyzed each
      image in random order and marked each lesion detected with a score, ranking from
      1 to 5 (1 definitely benign, 2 possibly benign, 3 undetermined, 4 possible HCC,
      and 5 definite HCC), then receiver operating characteristic (ROC) curve and Chi
      square analysis were adopted to compare the efficacy for MDCT and MRI imaging.
      RESULTS: Although no significant difference was demonstrated at the comparison of
      sensitivity and specificity (sensitivity and specificity of MDCT: 70%, 50%;
      sensitivity and specificity of MRI 86.36%, 100%; sensitivity chi2=0.835, P=0.360;
      specificity chi2=1.379, P=0.240), the Az (area under the ROC curve) for MRI
      imaging (mean, 0.974) was much higher than that for MDCT (mean, 0.795) with
      significant difference (P<0.05). CONCLUSION: MRI imaging shows better diagnostic
      accuracy for the detection of small HCC in patients with hepatitis B-induced
      cirrhosis and is recommended to improve the detection and diagnosis.

PMID- 21170115
TI  - Properties of small molecular drug loading and diffusion in a fluorinated PEG
      hydrogel studied by H molecular diffusion NMR and F spin diffusion NMR.
AB  - R(f)-PEG (fluoroalkyl double-ended poly(ethylene glycol)) hydrogel is potentially
      useful as a drug delivery depot due to its advanced properties of sol-gel two
      phase coexistence and low surface erosion. In this study, (1)H molecular
      diffusion nuclear magnetic resonance (NMR) and (19)F spin diffusion NMR were used
      to probe the drug loading and diffusion properties of the R(f)-PEG hydrogel for
      small anticancer drugs, 5-fluorouracil (FU) and its hydrophobic analog, 1,3
      dimethyl-5-fluorouracil (DMFU). It was found that FU has a larger apparent
      diffusion coefficient than that of DMFU, and the diffusion of the latter was more
      hindered. The result of (19)F spin diffusion NMR for the corresponding freeze
      dried samples indicates that a larger portion of DMFU resided in the R(f)
      core/IPDU intermediate-layer region (where IPDU refers to isophorone diurethane,
      as a linker to interconnect the R(f) group and the PEG chain) than that of FU
      while the opposite is true in the PEG-water phase. To understand the experimental
      data, a diffusion model was proposed to include: (1) hindered diffusion of the
      drug molecules in the R(f) core/IPDU-intermediate-layer region; (2) relatively
      free diffusion of the drug molecules in the PEG-water phase (or region); and (3)
      diffusive exchange of the probe molecules between the above two regions. This
      study also shows that molecular diffusion NMR combined with spin diffusion NMR is
      useful in studying the drug loading and diffusion properties in hydrogels for the
      purpose of drug delivery applications.

PMID- 21170113
TI  - Immunoproteomic analysis of human serological antibody responses to vaccination
      with whole-cell pertussis vaccine (WCV).
AB  - BACKGROUND: Pertussis (whooping cough) caused by Bordetella pertussis (B.p),
      continues to be a serious public health threat. Vaccination is the most
      economical and effective strategy for preventing and controlling pertussis.
      However, few systematic investigations of actual human immune responses to
      pertussis vaccines have been performed. Therefore, we utilized a combination of
      two-dimensional electrophoresis (2-DE), immunoblotting, and mass spectrometry to
      reveal the entire antigenic proteome of whole-cell pertussis vaccine (WCV)
      targeted by the human immune system as a first step toward evaluating the
      repertoire of human humoral immune responses against WCV. METHODOLOGY/PRINCIPAL
      FINDINGS: Immunoproteomic profiling of total membrane enriched proteins and
      extracellular proteins of Chinese WCV strain 58003 identified a total of 30
      immunoreactive proteins. Seven are known pertussis antigens including Pertactin,
      Serum resistance protein, chaperonin GroEL and two OMP porins. Sixteen have been
      documented to be immunogenic in other pathogens but not in B.p, and the
      immunogenicity of the last seven proteins was found for the first time.
      Furthermore, by comparison of the human and murine immunoproteomes of B.p, with
      the exception of four human immunoreactive proteins that were also reactive with
      mouse immune sera, a unique group of antigens including more than 20 novel
      immunoreactive proteins that uniquely reacted with human immune serum was
      confirmed. CONCLUSIONS/SIGNIFICANCE: This study is the first time that the
      repertoire of human serum antibody responses against WCV was comprehensively
      investigated, and a small number of previously unidentified antigens of WCV were
      also found by means of the classic immunoproteomic strategy. Further research on
      these newly identified predominant antigens of B.p exclusively against humans
      will not only remarkably accelerate the development of diagnostic biomarkers and
      subunit vaccines but also provide detailed insight into human immunity mechanisms
      against WCV. In particular, this work highlights the heterogeneity of the B.p
      immunoreactivity patterns of the mouse model and the human host.

PMID- 21170116
TI  - Sex in an Evolutionary Perspective: Just Another Reaction Norm.
AB  - It is common to refer to all sorts of clear-cut differences between the sexes as
      something that is biologically almost inevitable. Although this does not reflect
      the status of evolutionary theory on sex determination and sexual dimorphism, it
      is probably a common view among evolutionary biologists as well, because of the
      impact of sexual selection theory. To get away from thinking about biological sex
      and traits associated with a particular sex as something static, it should be
      recognized that in an evolutionary perspective sex can be viewed as a reaction
      norm, with sex attributes being phenotypically plastic. Sex determination itself
      is fundamentally plastic, even when it is termed "genetic". The phenotypic
      expression of traits that are statistically associated with a particular sex
      always has a plastic component. This plasticity allows for much more variation in
      the expression of traits according to sex and more overlap between the sexes than
      is typically acknowledged. Here we review the variation and frequency of
      evolutionary changes in sex, sex determination and sex roles and conclude that
      sex in an evolutionary time-frame is extremely variable. We draw on recent
      findings in sex determination mechanisms, empirical findings of morphology and
      behaviour as well as genetic and developmental models to explore the concept of
      sex as a reaction norm. From this point of view, sexual differences are not
      expected to generally fall into neat, discrete, pre-determined classes. It is
      important to acknowledge this variability in order to increase objectivity in
      evolutionary research.

PMID- 21170117
TI  - Is there a shift to "active nanostructures"?
AB  - It has been suggested that an important transition in the long-run trajectory of
      nanotechnology development is a shift from passive to active nanostructures. Such
      a shift could present different or increased societal impacts and require new
      approaches for risk assessment. An active nanostructure "changes or evolves its
      state during its operation," according to the National Science Foundation's
      (2006) Active Nanostructures and Nanosystems grant solicitation. Active
      nanostructure examples include nanoelectromechanical systems (NEMS),
      nanomachines, self-healing materials, targeted drugs and chemicals, energy
      storage devices, and sensors. This article considers two questions: (a) Is there
      a "shift" to active nanostructures? (b) How can we characterize the prototypical
      areas into which active nanostructures may emerge? We build upon the NSF
      definition of active nanostructures to develop a research publication search
      strategy, with a particular intent to distinguish between passive and active
      nanotechnologies. We perform bibliometric analyses and describe the main
      publication trends from 1995 to 2008. We then describe the prototypes of research
      that emerge based on reading the abstracts and review papers encountered in our
      search. Preliminary results suggest that there is a sharp rise in active
      nanostructures publications in 2006, and this rise is maintained in 2007 and
      through to early 2008. We present a typology that can be used to describe the
      kind of active nanostructures that may be commercialized and regulated in the
      future.

PMID- 21170118
TI  - Multicriteria mapping of stakeholder preferences in regulating nanotechnology.
AB  - In order to facilitate stakeholder discussions on how to regulate nanotechnology,
      the opensource program multicriteria mapping (MCM) was used to structure 26
      interviews with stakeholders in the USA. MCM offers a systematic part
      quantitative, part qualitative approach to clarify why some regulatory options
      (bans, moratoriums, voluntary measures, etc.) were deemed to be
      acceptable/unacceptable by various stakeholders and which criteria stakeholders
      used to evaluate the different regulatory options. Adopting an incremental
      approach and implementing a new regulatory framework was evaluated as the best
      options whereas a complete ban and no additional regulation of nanotechnology
      were found to be the least favorable. Criteria applied differed substantially
      among stakeholders and included social, ethical, regulatory, environmental, and
      health issues. Opinions on future regulation seem far less polarized than
      expected and it seems that stakeholders would welcome a combination of voluntary
      measures, an incremental approach and forming of a new regulatory framework.
      ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article
      (doi:10.1007/s11051-010-0006-3) contains supplementary material, which is
      available to authorized users.

PMID- 21170119
TI  - The slings and arrows of communication on nanotechnology.
AB  - According to numerous surveys the perceived risk of nanotechnology is low and
      most people feel that the benefits outweigh the risks. This article provides
      greater insight into risk perception and concludes that the positive attitude to
      nanotechnology is based not on knowledge but on hope and fascination. The
      perceived risk is low because of a lack of vivid and frightening images of
      possible hazards. If news flashes were to link nanotechnology to concrete hazards
      or actual harm to people, attitudes might suddenly change. Risk communication
      faces the problem of dealing with a public at large that has little or no
      knowledge about the technology. As it takes time and extensive additional
      research to develop appropriate communication strategies and disseminate them to
      the relevant institutions, this exercise should be started immediately.

PMID- 21170120
TI  - Comparison of the behaviour of manufactured and other airborne nanoparticles and
      the consequences for prioritising research and regulation activities.
AB  - Currently, there are no air quality regulations in force in any part of the world
      to control number concentrations of airborne atmospheric nanoparticles (ANPs).
      This is partly due to a lack of reliable information on measurement methods,
      dispersion characteristics, modelling, health and other environmental impacts.
      Because of the special characteristics of manufactured (also termed engineered or
      synthesised) nanomaterials or nanoparticles (MNPs), a substantial increase is
      forecast for their manufacture and use, despite understanding of safe design and
      use, and health and environmental implications being in its early stage. This
      article discusses a number of underlining technical issues by comparing the
      properties and behaviour of MNPs with anthropogenically produced ANPs. Such a
      comparison is essential for the judicious treatment of the MNPs in any potential
      air quality regulatory framework for ANPs.

PMID- 21170121
TI  - Nano Mapper: an Internet knowledge mapping system for nanotechnology development.
AB  - Nanotechnology research has experienced rapid growth in recent years. Advances in
      information technology enable efficient investigation of publications, their
      contents, and relationships for large sets of nanotechnology-related documents in
      order to assess the status of the field. This paper presents the development of a
      new knowledge mapping system, called Nano Mapper
      (http://nanomapper.eller.arizona.edu), which integrates the analysis of
      nanotechnology patents and research grants into a Web-based platform. The Nano
      Mapper system currently contains nanotechnology-related patents for 1976-2006
      from the United States Patent and Trademark Office (USPTO), European Patent
      Office (EPO), and Japan Patent Office (JPO), as well as grant documents from the
      U.S. National Science Foundation (NSF) for the same time period. The system
      provides complex search functionalities, and makes available a set of analysis
      and visualization tools (statistics, trend graphs, citation networks, and content
      maps) that can be applied to different levels of analytical units (countries,
      institutions, technical fields) and for different time intervals. The paper shows
      important nanotechnology patenting activities at USPTO for 2005-2006 identified
      through the Nano Mapper system.

PMID- 21170122
TI  - Comparative 3D QSAR study on beta(1)-, beta(2)-, and beta(3)-adrenoceptor
      agonists.
AB  - A quantitative structure-activity relationship study of tryptamine-based
      derivatives of beta(1)-, beta(2)-, and beta(3)-adrenoceptor agonists was
      conducted using comparative molecular field analysis (CoMFA). Correlation
      coefficients (cross-validated r(2)) of 0.578, 0.595, and 0.558 were obtained for
      the three subtypes, respectively, in three different CoMFA models. All three
      CoMFA models have different steric and electrostatic contributions, implying
      different requirements inside the binding cavity. The CoMFA coefficient contour
      plots of the three models and comparisons among these plots provide clues
      regarding the main chemical features responsible for the biological activity
      variations and also result in predictions which correlate very well with the
      observed biological activity. Based on the analysis, a summary regeospecific
      description of the requirements for improving beta-adrenoceptor subtype
      selectivity is given.

PMID- 21170123
TI  - Trends in worldwide nanotechnology patent applications: 1991 to 2008.
AB  - Nanotechnology patent applications published during 1991-2008 have been examined
      using the "title-abstract" keyword search on esp@cenet "worldwide" database. The
      longitudinal evolution of the number of patent applications, their topics, and
      their respective patent families have been evaluated for 15 national patent
      offices covering 98% of the total global activity. The patent offices of the
      United States (USA), People's Republic of China (PRC), Japan, and South Korea
      have published the largest number of nanotechnology patent applications, and
      experienced significant but different growth rates after 2000. In most
      repositories, the largest numbers of nanotechnology patent applications
      originated from their own countries/regions, indicating a significant "home
      advantage." The top applicant institutions are from different sectors in
      different countries (e.g., from industry in the US and Canada patent offices, and
      from academe or government agencies at the PRC office). As compared to 2000, the
      year before the establishment of the US National Nanotechnology Initiative (NNI),
      numerous new invention topics appeared in 2008, in all 15 patent repositories.
      This is more pronounced in the USA and PRC. Patent families have increased among
      the 15 patent offices, particularly after 2005. Overlapping patent applications
      increased from none in 1991 to about 4% in 2000 and to about 27% in 2008. The
      largest share of equivalent nanotechnology patent applications (1,258) between
      two repositories was identified between the US and Japan patent offices.

PMID- 21170124
TI  - How interdisciplinary is nanotechnology?
AB  - Facilitating cross-disciplinary research has attracted much attention in recent
      years, with special concerns in nanoscience and nanotechnology. Although policy
      discourse has emphasized that nanotechnology is substantively integrative, some
      analysts have countered that it is really a loose amalgam of relatively
      traditional pockets of physics, chemistry, and other disciplines that interrelate
      only weakly. We are developing empirical measures to gauge and visualize the
      extent and nature of interdisciplinary interchange. Such results speak to
      research organization, funding, and mechanisms to bolster knowledge transfer. In
      this study, we address the nature of cross-disciplinary linkages using "science
      overlay maps" of articles, and their references, that have been categorized into
      subject categories. We find signs that the rate of increase in nano research is
      slowing, and that its composition is changing (for one, increasing chemistry
      related activity). Our results suggest that nanotechnology research encompasses
      multiple disciplines that draw knowledge from disciplinarily diverse knowledge
      sources. Nano research is highly, and increasingly, integrative-but so is much of
      science these days. Tabulating and mapping nano research activity show a dominant
      core in materials sciences, broadly defined. Additional analyses and maps show
      that nano research draws extensively upon knowledge presented in other areas; it
      is not constricted within narrow silos.

PMID- 21170125
TI  - Making sense of policy choices: understanding the roles of value predispositions,
      mass media, and cognitive processing in public attitudes toward nanotechnology.
AB  - Using a nationally representative telephone survey of 1,015 adults in the United
      States, this study examines how value predispositions, communication variables,
      and perceptions of risks and benefits are associated with public support for
      federal funding of nanotechnology. Our findings show that highly religious
      individuals were less supportive of funding of nanotech than less religious
      individuals, whereas individuals who held a high deference for scientific
      authority were more supportive of funding of the emerging technology than those
      low in deference. Mass media use and elaborative processing of scientific news
      were positively associated with public support for funding, whereas factual
      scientific knowledge had no significant association with policy choices. The
      findings suggest that thinking about and reflecting upon scientific news promote
      better understanding of the scientific world and may provide a more sophisticated
      cognitive structure for the public to form opinions about nanotech than factual
      scientific knowledge. Finally, heuristic cues including trust in scientists and
      perceived risks and benefits of nanotech were found to be associated with public
      support for nanotech funding. We conclude with policy implications that will be
      useful for policymakers and science communication practitioners.

PMID- 21170126
TI  - The morality of attitudes toward nanotechnology: about God, techno-scientific
      progress, and interfering with nature.
AB  - Using survey data, we examine public attitudes toward and awareness of
      nanotechnology in Germany (N = 750). First, it is shown that a majority of the
      people are still not familiar with nanotechnology. In addition, diffusion of
      information about nanotechnology thus far mostly seems to reach men and people
      with a relative higher educational background. Also, pro-science and technology
      views are positively related with nanotech familiarity. Results further show that
      a majority of the people have an indifferent, ambiguous, or non-attitude toward
      nanotechnology. Multinomial logit analyses further reveal that nanotech
      familiarity is positively related with people's attitudes. In addition, it is
      shown that traditional religiosity is unrelated to attitudes and that individual
      religiosity is weakly related to nanotechnology attitudes. However, moral
      covariates other than religiosity seem of major importance. In particular, our
      results show that more negative views on technological and scientific progress as
      well as more holistic views about the relation between people and the environment
      increase the likelihood of having a negative attitude toward nanotechnology.

PMID- 21170127
TI  - Redefining risk research priorities for nanomaterials.
AB  - Chemical-based risk assessment underpins the current approach to responsible
      development of nanomaterials (NM). It is now recognised, however, that this
      process may take decades, leaving decision makers with little support in the near
      term. Despite this, current and near future research efforts are largely directed
      at establishing (eco)toxicological and exposure data for NM, and comparatively
      little research has been undertaken on tools or approaches that may facilitate
      near-term decisions, some of which we briefly outline in this analysis. We
      propose a reprioritisation of NM risk research efforts to redress this imbalance,
      including the development of more adaptive risk governance frameworks,
      alternative/complementary tools to risk assessment, and health and environment
      surveillance.

PMID- 21170128
TI  - Trends for nanotechnology development in China, Russia, and India.
AB  - China, Russia, and India are playing an increasingly important role in global
      nanotechnology research and development (R&D). This paper comparatively inspects
      the paper and patent publications by these three countries in the Thomson Science
      Citation Index Expanded (SCI) database and United States Patent and Trademark
      Office (USPTO) database (1976-2007). Bibliographic, content map, and citation
      network analyses are used to evaluate country productivity, dominant research
      topics, and knowledge diffusion patterns. Significant and consistent growth in
      nanotechnology papers are noted in the three countries. Between 2000 and 2007,
      the average annual growth rate was 31.43% in China, 11.88% in Russia, and 33.51%
      in India. During the same time, the growth patterns were less consistent in
      patent publications: the corresponding average rates are 31.13, 10.41, and 5.96%.
      The three countries' paper impact measured by the average number of citations has
      been lower than the world average. However, from 2000 to 2007, it experienced
      rapid increases of about 12.8 times in China, 8 times in India, and 1.6 times in
      Russia. The Chinese Academy of Sciences (CAS), the Russian Academy of Sciences
      (RAS), and the Indian Institutes of Technology (IIT) were the most productive
      institutions in paper publication, with 12,334, 6,773, and 1,831 papers,
      respectively. The three countries emphasized some common research topics such as
      "Quantum dots," "Carbon nanotubes," "Atomic force microscopy," and "Scanning
      electron microscopy," while Russia and India reported more research on nano
      devices as compared with China. CAS, RAS, and IIT played key roles in the
      respective domestic knowledge diffusion.

PMID- 21170129
TI  - Nanotoxicology: characterizing the scientific literature, 2000-2007.
AB  - Understanding the toxicity of nanomaterials and nano-enabled products is
      important for human and environmental health and safety as well as public
      acceptance. Assessing the state of knowledge about nanotoxicology is an important
      step in promoting comprehensive understanding of the health and environmental
      implications of these new materials. To this end, we employed bibliometric
      techniques to characterize the prevalence and distribution of the current
      scientific literature. We found that the nano-toxicological literature is
      dispersed across a range of disciplines and sub-fields; focused on in vitro
      testing; often does not specify an exposure pathway; and tends to emphasize acute
      toxicity and mortality rather than chronic exposure and morbidity. Finally, there
      is very little research on consumer products, particularly on their environmental
      fate, and most research is on the toxicity of basic nanomaterials. The
      implications for toxicologists, regulators and social scientists studying
      nanotechnology and society are discussed.

PMID- 21170130
TI  - Risk perceptions starting to shift? U.S. citizens are forming opinions about
      nanotechnology.
AB  - This article presents early results from an opinion formation study based on a 76
      member panel of U.S. citizens, with comparison data from a group of 177
      nanotechnology experts. While initially similar to the expert group in terms of
      their perceptions of the risks, benefits, and need for regulation characterizing
      several forms of nanotechnology, the first follow-up survey indicates that the
      panel is beginning to diverge from the experts, particularly with respect to
      perceptions of the levels of various "societal" risks that nanotechnology might
      present. The data suggest that responding to public concerns may involve more
      than attention to physical risks in areas such as health and environment;
      concerns about other forms of risk actually appear more salient.

PMID- 21170131
TI  - Toxicity and cellular uptake of gold nanoparticles: what we have learned so far?
AB  - Gold nanoparticles have attracted enormous scientific and technological interest
      due to their ease of synthesis, chemical stability, and unique optical
      properties. Proof-of-concept studies demonstrate their biomedical applications in
      chemical sensing, biological imaging, drug delivery, and cancer treatment.
      Knowledge about their potential toxicity and health impact is essential before
      these nanomaterials can be used in real clinical settings. Furthermore, the
      underlying interactions of these nanomaterials with physiological fluids is a key
      feature of understanding their biological impact, and these interactions can
      perhaps be exploited to mitigate unwanted toxic effects. In this Perspective we
      discuss recent results that address the toxicity of gold nanoparticles both in
      vitro and in vivo, and we provide some experimental recommendations for future
      research at the interface of nanotechnology and biological systems.

PMID- 21170132
TI  - The changing information environment for nanotechnology: online audiences and
      content.
AB  - The shift toward online communication in all realms, from print newspapers to
      broadcast television, has implications for how the general public consumes
      information about nanotechnology. The goal of this study is threefold: to
      investigate who is using online sources for information and news about science
      and nanotechnology, to examine what the general public is searching for online
      with regards to nanotechnology, and to analyze what they find in online content
      of nanotechnology. Using survey data, we find those who report the Internet as
      their primary source of science and technology news are diverse in age, more
      knowledgeable about science and nanotechnology, highly educated, male, and more
      diverse racially than users of other media. In a comparison of demographic data
      on actual visits by online users to general news and science Web sites, science
      sites attracted more male, non-white users from the Western region of the United
      States than news sites did. News sites, on the other hand, attracted those with a
      slightly higher level of education. Our analysis of published estimates of
      keyword searches on nanotechnology reveals people are turning to the Internet to
      search for keyword searches related to the future, health, and applications of
      nanotechnology. A content analysis of online content reveals health content
      dominates overall. Comparisons of content in different types of sites-blogs,
      government, and general sites-are conducted. ELECTRONIC SUPPLEMENTARY MATERIAL:
      The online version of this article (doi:10.1007/s11051-010-9860-2) contains
      supplementary material, which is available to authorized users.

PMID- 21170134
TI  - Developing nanotechnology in Latin America.
AB  - This article investigates the development of nanotechnology in Latin America with
      a particular focus on Argentina, Brazil, Chile, and Uruguay. Based on data for
      nanotechnology research publications and patents and suggesting a framework for
      analyzing the development of R&D networks, we identify three potential strategies
      of nanotechnology research collaboration. Then, we seek to identify the balance
      of emphasis upon each of the three strategies by mapping the current research
      profile of those four countries. In general, we find that they are implementing
      policies and programs to develop nanotechnologies but differ in their
      collaboration strategies, institutional involvement, and level of development. On
      the other hand, we find that they coincide in having a modest industry
      participation in research and a low level of commercialization of
      nanotechnologies.

PMID- 21170133
TI  - In quest of a systematic framework for unifying and defining nanoscience.
AB  - This article proposes a systematic framework for unifying and defining
      nanoscience based on historic first principles and step logic that led to a
      "central paradigm" (i.e., unifying framework) for traditional elemental/small
      molecule chemistry. As such, a Nanomaterials classification roadmap is proposed,
      which divides all nanomatter into Category I: discrete, well-defined and Category
      II: statistical, undefined nanoparticles. We consider only Category I, well
      defined nanoparticles which are >90% monodisperse as a function of Critical
      Nanoscale Design Parameters (CNDPs) defined according to: (a) size, (b) shape,
      (c) surface chemistry, (d) flexibility, and (e) elemental composition. Classified
      as either hard (H) (i.e., inorganic-based) or soft (S) (i.e., organic-based)
      categories, these nanoparticles were found to manifest pervasive atom mimicry
      features that included: (1) a dominance of zero-dimensional (0D) core-shell
      nanoarchitectures, (2) the ability to self-assemble or chemically bond as
      discrete, quantized nanounits, and (3) exhibited well-defined nanoscale valencies
      and stoichiometries reminiscent of atom-based elements. These discrete
      nanoparticle categories are referred to as hard or soft particle nanoelements.
      Many examples describing chemical bonding/assembly of these nanoelements have
      been reported in the literature. We refer to these hard:hard (H-n:H-n), soft:soft
      (S-n:S-n), or hard:soft (H-n:S-n) nanoelement combinations as nanocompounds. Due
      to their quantized features, many nanoelement and nanocompound categories are
      reported to exhibit well-defined nanoperiodic property patterns. These periodic
      property patterns are dependent on their quantized nanofeatures (CNDPs) and
      dramatically influence intrinsic physicochemical properties (i.e., melting
      points, reactivity/self-assembly, sterics, and nanoencapsulation), as well as
      important functional/performance properties (i.e., magnetic, photonic,
      electronic, and toxicologic properties). We propose this perspective as a modest
      first step toward more clearly defining synthetic nanochemistry as well as
      providing a systematic framework for unifying nanoscience. With further progress,
      one should anticipate the evolution of future nanoperiodic table(s) suitable for
      predicting important risk/benefit boundaries in the field of nanoscience.
      ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article
      (doi:10.1007/s11051-009-9632-z) contains supplementary material, which is
      available to authorized users.

PMID- 21170135
TI  - Spectroscopic ellipsometry and polarimetry for materials and systems analysis at
      the nanometer scale: state-of-the-art, potential, and perspectives.
AB  - This paper discusses the fundamentals, applications, potential, limitations, and
      future perspectives of polarized light reflection techniques for the
      characterization of materials and related systems and devices at the nanoscale.
      These techniques include spectroscopic ellipsometry, polarimetry, and reflectance
      anisotropy. We give an overview of the various ellipsometry strategies for the
      measurement and analysis of nanometric films, metal nanoparticles and nanowires,
      semiconductor nanocrystals, and submicron periodic structures. We show that
      ellipsometry is capable of more than the determination of thickness and optical
      properties, and it can be exploited to gain information about process control,
      geometry factors, anisotropy, defects, and quantum confinement effects of
      nanostructures.

PMID- 21170136
TI  - Of risks and regulations: how leading U.S. nanoscientists form policy stances
      about nanotechnology.
AB  - Even though there is a high degree of scientific uncertainty about the risks of
      nanotechnology, many scholars have argued that policy-making cannot be placed on
      hold until risk assessments are complete (Faunce, Med J Aust 186(4):189-191,
      2007; Kuzma, J Nanopart Res 9(1):165-182, 2007; O'Brien and Cummins, Hum Ecol
      Risk Assess 14(3):568-592, 2008; Powell et al., Environ Manag 42(3):426-443,
      2008). In the absence of risk assessment data, decision makers often rely on
      scientists' input about risks and regulation to make policy decisions. The
      research we present here goes beyond the earlier descriptive studies about
      nanotechnology regulation to explore the heuristics that the leading U.S.
      nanoscientists use when they make policy decisions about regulating
      nanotechnology. In particular, we explore the relationship between
      nanoscientists' risk and benefit perceptions and their support for nanotech
      regulation. We conclude that nanoscientists are more supportive of regulating
      nanotechnology when they perceive higher levels of risks; yet, their perceived
      benefits about nanotechnology do not significantly impact their support for
      nanotech regulation. We also find some gender and disciplinary differences among
      the nanoscientists. Males are less supportive of nanotech regulation than their
      female peers and materials scientists are more supportive of nanotechnology
      regulation than scientists in other fields. Lastly, our findings illustrate that
      the leading U.S. nanoscientists see the areas of surveillance/privacy, human
      enhancement, medicine, and environment as the nanotech application areas that are
      most in need of new regulations.

PMID- 21170137
TI  - Where do omics and markers go next?

PMID- 21170138
TI  - Temperature-Dependent Site Control of InAs/GaAs (001) Quantum Dots Using a
      Scanning Tunneling Microscopy Tip During Growth.
AB  - Site-controlled InAs nano dots were successfully fabricated by a STMBE system (in
      situ scanning tunneling microscopy during molecular beam epitaxy growth) at
      substrate temperatures from 50 to 430 degrees C. After 1.5 ML of the InAs wetting
      layer (WL) growth by ordinal Stranski-Krastanov dot fabrication procedures, we
      applied voltage at particular sites on the InAs WL, creating the site where In
      atoms, which were migrating on the WL, favored to congregate. At 240 degrees C,
      InAs nano dots (width: 20-40 nm, height: 1.5-2.0 nm) were fabricated. At 430
      degrees C, InAs nano dots (width: 16-20 nm, height: 0.75-1.5 nm) were also
      fabricated. However, these dots were remained at least 40 s and collapsed less
      than 1000 s. Then, we fabricated InAs nano dots (width: 24-150 nm, height: 2.8-28
      nm) at 300 degrees C under In and As(4) irradiations. These were not collapsed
      and considered to high crystalline dots. 

PMID- 21170139
TI  - Morphology Analysis of Si Island Arrays on Si(001).
AB  - The formation of nanometer-scale islands is an important issue for bottom-up
      based schemes in novel electronic, optoelectronic and magnetoelectronic devices
      technology. In this work, we present a detailed atomic force microscopy analysis
      of Si island arrays grown by molecular beam epitaxy. Recent reports have shown
      that self-assembled distributions of fourfold pyramid-like islands develop in 5
      nm thick Si layers grown at substrate temperatures of 650 and 750 degrees C on HF
      prepared Si(001) substrates. Looking for wielding control and understanding the
      phenomena involved in this surface nanostructuring, we develop and apply a
      formalism that allows for processing large area AFM topographic images in a shot,
      obtaining surface orientation maps with specific information on facets
      population. The procedure reveals some noticeable features of these Si island
      arrays, e.g. a clear anisotropy of the in-plane local slope distributions. Total
      island volume analysis also indicates mass transport from the substrate surface
      to the 3D islands, a process presumably related to the presence of trenches
      around some of the pyramids. Results are discussed within the framework of
      similar island arrays in homoepitaxial and heteroepitaxial semiconductor systems.

PMID- 21170140
TI  - Filtering of Defects in Semipolar (11-22) GaN Using 2-Steps Lateral Epitaxial
      Overgrowth.
AB  - Good-quality (11-22) semipolar GaN sample was obtained using epitaxial lateral
      overgrowth. The growth conditions were chosen to enhance the growth rate along
      the [0001] inclined direction. Thus, the coalescence boundaries stop the
      propagation of basal stacking faults. The faults filtering and the improvement of
      the crystalline quality were attested by transmission electron microscopy and low
      temperature photoluminescence. The temperature dependence of the luminescence
      polarization under normal incidence was also studied. 

PMID- 21170141
TI  - In situ Control of Si/Ge Growth on Stripe-Patterned Substrates Using Reflection
      High-Energy Electron Diffraction and Scanning Tunneling Microscopy.
AB  - Si and Ge growth on the stripe-patterned Si (001) substrates is studied using in
      situ reflection high-energy electron diffraction (RHEED) and scanning tunneling
      microscopy (STM). During Si buffer growth, the evolution of RHEED patterns
      reveals a rapid change of the stripe morphology from a multifaceted "U" to a
      single-faceted "V" geometry with {119} sidewall facets. This allows to control
      the pattern morphology and to stop Si buffer growth once a well-defined stripe
      geometry is formed. Subsequent Ge growth on "V"-shaped stripes was performed at
      two different temperatures of 520 and 600 degrees C. At low temperature of 520
      degrees C, pronounced sidewall ripples are formed at a critical coverage of 4.1
      monolayers as revealed by the appearance of splitted diffraction streaks in
      RHEED. At 600 degrees C, the ripple onset is shifted toward higher coverages, and
      at 5.2 monolayers dome islands are formed at the bottom of the stripes. These
      observations are in excellent agreement with STM images recorded at different Ge
      coverages. Therefore, RHEED is an efficient tool for in situ control of the
      growth process on stripe-patterned substrate templates. The comparison of the
      results obtained at different temperature reveals the importance of kinetics on
      the island formation process on patterned substrates. 

PMID- 21170142
TI  - Models of the reading process.
AB  - Reading is a complex skill involving the orchestration of a number of components.
      Researchers often talk about a 'model of reading' when talking about only one
      aspect of the reading process (e.g., models of word identification are often
      referred to as 'models of reading'). Here, we review prominent models that are
      designed to account for (1) word identification, (2) syntactic parsing, (3)
      discourse representations, and (4) how certain aspects of language processing
      (e.g., word identification), in conjunction with other constraints (e.g., limited
      visual acuity, saccadic error) guide readers' eyes. Unfortunately, it is the case
      that these various models addressing specific aspects of the reading process
      seldom make contact with models dealing with other aspects of reading. Thus, for
      example, the models of word identification seldom make contact with models of eye
      movement control, and vice versa. Although this may be unfortunate in some ways,
      it is quite understandable in other ways because reading itself is a very complex
      process. We discuss prototypical models of aspects of the reading process in the
      order mentioned above. We do not review all possible models but rather focus on
      those we view as being representative and most highly recognized. WIREs Cogn Sci
      2010 1 787-799 This article is categorized under: Linguistics > Computational
      Models of Language Psychology > Language.

PMID- 21170144
TI  - Convenient one-pot synthesis of trans-1,2-diaryloxiranes from the direct coupling
      of benzyl halides.
AB  - trans-1,2-Diaryloxiranes were conveniently prepared in an one-pot reaction by the
      direct coupling of benzyl halides in the presence of silver oxide and DMSO under
      mild conditions.

PMID- 21170143
TI  - Patients' Reasons for Choosing Office-based Buprenorphine: Preference for Patient
      Centered Care.
AB  - OBJECTIVES: To explore HIV-infected patients' attitudes about buprenorphine
      treatment in office-based and opioid treatment program (OTP) settings. METHODS:
      We conducted in-depth qualitative interviews with 29 patients with co-existing
      HIV infection and opioid dependence seeking buprenorphine maintenance therapy in
      office-based and OTP settings. We used thematic analysis of transcribed
      audiorecorded interviews to identify themes. RESULTS: Patients voiced a strong
      preference for office-based treatment. Four themes emerged to explain this
      preference. First, patients perceived the greater convenience of office-based
      treatment as improving their ability to address HIV and other healthcare issues.
      Second, they perceived a strong patient-focused orientation in patient-provider
      relationships underpinning their preference for office-based care. This was
      manifest as increased trust, listening, empathy, and respect from office-based
      staff and providers. Third, they perceived shared power and responsibility in
      office-based settings. Finally, patients viewed office-based treatment as a more
      supportive environment for sobriety and relapse prevention. This was partly due
      to strong therapeutic alliances with office-based staff and providers who
      prioritized a harm reduction approach, but also due to the perception that the
      office-based settings were "safer" for sobriety, compared with increased
      opportunities for purchasing and using illicit opiates in OTP settings.
      CONCLUSIONS: HIV-infected patients with opioid dependence preferred office-based
      buprenorphine because they perceived it as offering a more patient-centered
      approach to care compared with OTP referral. Office-based buprenorphine may
      facilitate engagement in care for patients with co-existing opioid dependence and
      HIV infection.

PMID- 21170145
TI  - The Effect of Capital Gains Taxation on Home Sales: Evidence from the Taxpayer
      Relief Act of 1997.
AB  - The Taxpayer Relief Act of 1997 (TRA97) significantly changed the tax treatment
      of housing capital gains in the United States. Before 1997, homeowners were
      subject to capital gains taxation when they sold their houses unless they
      purchased replacement homes of equal or greater value. Since 1997, homeowners can
      exclude capital gains of $500,000 (or $250,000 for single filers) when they sell
      their houses. Such dramatic changes provide a good opportunity to study the lock
      in effect of capital gains taxation on home sales. Using 1982-2008 transaction
      data on single-family houses in 16 affluent towns within the Boston metropolitan
      area, I find that TRA97 reversed the lock-in effect of capital gains taxes on
      houses with low and moderate capital gains. Specifically, the semiannual sales
      rate of houses with positive gains up to $500,000 increased by 0.40-0.62
      percentage points after TRA97, representing a 19-24 percent increase from the pre
      TRA97 baseline sales rate. In contrast, I do not find TRA97 to have a significant
      effect on houses with gains above $500,000. Moreover, the short-term effect of
      TRA97 is much larger than the long-term effect, suggesting that many previously
      locked-in homeowners took advantage of the exclusions immediately after TRA97. In
      addition, I exploit the 2001 and 2003 legislative changes in the capital gains
      tax rate to estimate the tax elasticity of home sales during the post-TRA97
      period. The estimation results suggest that a $10,000 increase in capital gains
      taxes reduces the semiannual home sales rate by about 0.1-0.2 percentage points,
      or 6-13 percent from the post-TRA97 average sales rate.

PMID- 21170147
TI  - Measuring pregnancy planning: An assessment of the London Measure of Unplanned
      Pregnancy among urban, south Indian women.
AB  - We evaluated the psychometric properties of the London Measure of Unplanned
      Pregnancy among Indian women using classical methods and Item Response Modeling.
      The scale exhibited good internal consistency and internal structure, with
      overall scores correlating well with each item's response categories. Items
      performed similarly for pregnant and non-pregnant women, and scores decreased
      with increasing parity, providing evidence for validity. Analyses also detected
      limitations, including infrequent selection of middle response categories and
      some evidence of differential item functioning by parity. We conclude that the
      LMUP represents an improvement over existing measures but recommend steps for
      enhancing scale performance for this cultural context.

PMID- 21170146
TI  - Refilling Intracellular Calcium Stores.
AB  - Within the cardiac cell, the movements of calcium ions are tightly regulated by a
      number of regulatory proteins including pumps, and channels. The sarcoplasmic
      reticulum (SR) is in large part responsible for orchestrating these movements for
      the normal functioning of the cardiomyocyte. Alterations of SR regulatory
      proteins in failing hearts leads to abnormal Ca(2+) homeostasis and consequently
      to a deficient contractile state. This review focuses on the roles of SR Ca(2+)
      regulators in disease states and novel strategies for therapeutic targeting of
      these pathways.

PMID- 21170148
TI  - Tests of Hypotheses Arising In the Correlated Random Coefficient Model.
AB  - This paper examines the correlated random coefficient model. It extends the
      analysis of Swamy (1971), who pioneered the uncorrelated random coefficient model
      in economics. We develop the properties of the correlated random coefficient
      model and derive a new representation of the variance of the instrumental
      variable estimator for that model. We develop tests of the validity of the
      correlated random coefficient model against the null hypothesis of the
      uncorrelated random coefficient model.

PMID- 21170150
TI  - Dihydro-3-(triphenylphosphoranylidene)-2,5-thiophendione: A Convenient Synthon
      for the Preparation of Substituted 1,4-Thiazepin-5-ones and Piperidinones via the
      Intermediacy of Thioacids.
AB  - Reaction of thiomaleic anhydride with triphenylphosphine gives the title compound
      which undergoes reaction with a variety of aldehydes to give a range of
      alkylidene thiomaleic anhydrides (substituted monothio itaconic anhydrides).
      Subsequent treatment with tert-butoxycarbonylamino-substituted thiols, or under
      radical conditions with tert-butoxycarbonylamino-substituted alkyl halides
      results in a series of substituted monothiomaleic anhydrides, that on exposure to
      trifluoroacetic acid and then base lead to thiocarboxyl substituted 1,4-thiazepin
      5-ones and piperidinones, respectively, that are ultimately trapped by reaction
      with 2,4-dinitrobenzenesulfonamides to give the corresponding amides.

PMID- 21170149
TI  - Recent insights into the pathophysiology of preeclampsia.
AB  - Preeclampsia, characterized by new-onset gestational hypertension and
      proteinuria, is a common and serious complication of pregnancy. Evidence from
      both animal and human studies has implicated placental ischemia and hypoxia as a
      central causative factor in the etiology of the disorder. The ischemic placenta
      in turn initiates a cascade of secondary effector mechanisms, including altered
      proangiogenic and antiangiogenic factor balance, increase in maternal oxidative
      stress and endothelial and immunological dysfunction. The full elucidation of
      these mechanisms will hopefully lead to a more complete understanding of the
      etiology of preeclampsia and lead to successful therapeutic intervention through
      the targeted disruption of new and novel pathways.

PMID- 21170152
TI  - NONPARAMETRIC COVARIANCE MODEL.
AB  - There has been considerable attention on estimation of conditional variance
      function in the literature. We propose here a nonparametric model for conditional
      covariance matrix. A kernel estimator is developed accordingly, its asymptotic
      bias and variance are derived, and its asymptotic normality is established. A
      real data example is used to illustrate the proposed estimation procedure.

PMID- 21170151
TI  - p38gamma regulates UV-induced checkpoint signaling and repair of UV-induced DNA
      damage.
AB  - In eukaryotic cells, DNA damage triggers activation of checkpoint signaling
      pathways that coordinate cell cycle arrest and repair of damaged DNA. These DNA
      damage responses serve to maintain genome stability and prevent accumulation of
      genetic mutations and development of cancer. The p38 MAPK was previously
      implicated in cellular responses to several types of DNA damage. However, the
      role of each of the four p38 isoforms and the mechanism for their involvement in
      DNA damage responses remained poorly understood. In this study, we demonstrate
      that p38gamma, but not the other p38 isoforms, contributes to the survival of UV
      treated cells. Deletion of p38gamma sensitizes cells to UV exposure, accompanied
      by prolonged S phase cell cycle arrest and increased rate of apoptosis. Further
      investigation reveal that p38gamma is essential for the optimal activation of the
      checkpoint signaling caused by UV, and for the efficient repair of UV-induced DNA
      damage. These findings have established a novel role of p38gamma in UV-induced
      DNA damage responses, and suggested that p38gamma contributes to the ability of
      cells to cope with UV exposure by regulating the checkpoint signaling pathways
      and the repair of damaged DNA.

PMID- 21170153
TI  - Finite Normal Mixture SEM Analysis by Fitting Multiple Conventional SEM Models.
AB  - This paper proposes a two-stage maximum likelihood (ML) approach to normal
      mixture structural equation modeling (SEM), and develops statistical inference
      that allows distributional misspecification. Saturated means and covariances are
      estimated at stage-1 together with a sandwich-type covariance matrix. These are
      used to evaluate structural models at stage-2. Techniques accumulated in the
      conventional SEM literature for model diagnosis and evaluation can be used to
      study the model structure for each component. Examples show that the two-stage ML
      approach leads to correct or nearly correct models even when the normal mixture
      assumptions are violated and initial models are misspecified. Compared to single
      stage ML, two-stage ML avoids the confounding effect of model specification and
      the number of components, and is computationally more efficient. Monte-Carlo
      results indicate that two-stage ML loses only minimal efficiency under the
      condition where single-stage ML performs best. Monte-Carlo results also indicate
      that the commonly used model selection criterion BIC is more robust to
      distribution violations for the saturated model than that for a structural model
      at moderate sample sizes. The proposed two-stage ML approach is also extremely
      flexible in modeling different components with different models. Potential new
      developments in the mixture modeling literature can be easily adapted to study
      issues with normal mixture SEM.

PMID- 21170154
TI  - Depression history, depression vulnerability and the experience of everyday
      negative events.
AB  - This study examined whether deficits in dealing with daily problems emerge before
      a depressive episode (i.e., pre-existing vulnerability) or after a depressive
      episode (i.e., psychosocial scar). Participants completed a 30-day daily diary in
      which they reported their most negative event of the day, their appraisals of
      that event, and their mood. Three years later, they completed a structured
      depression interview. The sample consisted of 350 college students, 24 of whom
      had a past history of depression and 54 of whom experienced a depressive episode
      subsequent to dairy completion. Multilevel modeling revealed that students with
      past depression blamed others more than the never-depressed and those with
      subsequent depression, which supported the scar hypothesis. In support of the
      vulnerability hypothesis, as compared to the never-depressed group, participants
      with past depression demonstrated steeper declines in positive mood on more
      stressful days but did not significantly differ from the subsequent depression
      group. Overall, our findings do not provide clear support for either hypothesis;
      however, this study is the first to use a daily diary design to directly compare
      individuals with past depression to individuals who would subsequently experience
      depression.

PMID- 21170155
TI  - Psychosocial Adjustment and Substance Use of Cambodian and Vietnamese Immigrant
      Youth.
AB  - Southeast Asians living in the United States are a unique Asian immigrant
      population. They are considered one of the "newer" Asian immigrant groups, tend
      to be less affluent compared with their East and South Asian counterparts, and
      are steadily growing in number (U.S. Bureau of the Census, 2000). Unfortunately,
      few studies exist specifically about Southeast Asian immigrants. The lack of
      studies, coupled with the community's growing mental health issues, suggests the
      need for increased research on this population. This study contributes to the
      literature by examining the extent to which identification with Vietnamese or
      Cambodian culture, peer relationships, and coping behaviors affect substance use
      among Cambodian and Vietnamese immigrant youth. A sample of 102 participants, age
      12-18 years, completed self-report measures regarding these variables. Overall,
      results indicate that identification with one's culture of origin and coping
      behaviors moderate the relationship between deviant peer association and
      substance use. Results are discussed within a contextual model of problem
      behavior among Southeast Asian youth.

PMID- 21170156
TI  - Absence of Metallothionein 3 Expression in Breast Cancer is a Rare, But Favorable
      Marker of Outcome that is Under Epigenetic Control.
AB  - Cadmium (Cd(+2)), a known carcinogen mimics the effects of estrogen in the uterus
      and mammary gland suggesting its possible involvement in the development and
      progression of breast cancer. This lab showed through analysis of a small set of
      archival human diagnostic specimens that the third isoform of the classic Cd(+2)
      binding protein metallothionein (MT-3), is not expressed in normal breast tissue,
      but is expressed in some breast cancers and that expression tends to correlate
      with a poor disease outcome. The goals of the present study were to verify that
      overexpression of MT-3 in a large set of archival human diagnostic specimens
      tends to correlate with poor disease outcome and define the mechanism of MT-3
      gene regulation in the normal breast epithelial cell. The results showed that MT
      3 was expressed in approximately 90% of all breast cancers and was absent in
      normal breast epithelium. The lack of MT-3 staining in some cancers correlated
      with a favorable patient outcome. High frequency of MT-3 staining was also found
      for in situ breast cancer suggesting that MT-3 might be an early biomarker for
      breast cancer. The study also demonstrated that the MCF-10A cell line, an
      immortalized, non-tumorigenic model of human breast epithelial cells, displayed
      no basal expression of MT-3, nor was it induced by Cd(+2). Treatment of the MCF
      10A cells with the demethylation agent, 5-Aza-2'-deoxycytidine, or the histone
      deacetylase inhibitor, MS-275, restored MT-3 mRNA expression. It was also shown
      that the MT-3 metal regulatory elements are potentially active binders of protein
      factors following treatment with these inhibitors suggesting that MT-3 expression
      may be subject to epigenetic regulation.

PMID- 21170157
TI  - Signal recognition by frogs in the presence of temporally fluctuating chorus
      shaped noise.
AB  - The background noise generated in large social aggregations of calling
      individuals is a potent source of auditory masking for animals that communicate
      acoustically. Despite similarities with the so-called "cocktail-party problem" in
      humans, few studies have explicitly investigated how non-human animals solve the
      perceptual task of separating biologically relevant acoustic signals from ambient
      background noise. Under certain conditions, humans experience a release from
      auditory masking when speech is presented in speech-like masking noise that
      fluctuates in amplitude. We tested the hypothesis that females of Cope's gray
      treefrog (Hyla chrysoscelis) experience masking release in artificial chorus
      noise that fluctuates in level at modulations rates characteristic of those
      present in ambient chorus noise. We estimated thresholds for recognizing
      conspecific advertisement calls (pulse rate=40-50 pulses/s) in the presence of
      unmodulated and sinusoidally amplitude modulated (SAM) chorus-shaped masking
      noise. We tested two rates of modulation (5 Hz and 45 Hz) because the sounds of
      frog choruses are modulated at low rates (e.g., less than 5-10 Hz), and because
      those of species with pulsatile signals are additionally modulated at higher
      rates typical of the pulse rate of calls (e.g., between 15-50 Hz). Recognition
      thresholds were similar in the unmodulated and 5-Hz SAM conditions, and 12 dB
      higher in the 45-Hz SAM condition. These results did not support the hypothesis
      that female gray treefrogs experience masking release in temporally fluctuating
      chorus-shaped noise. We discuss our results in terms of modulation masking, and
      hypothesize that natural amplitude fluctuations in ambient chorus noise may
      impair mating call perception.

PMID- 21170158
TI  - Lift-off PMN-PT Thick Film for High Frequency Ultrasonic Biomicroscopy.
AB  - Piezoelectric 0.65Pb(Mg(1/3)Nb(2/3))O(3)-0.35PbTiO(3) (PMN-35PT) thick film with
      a thickness of approximately 12 um has been deposited on the platinum buffered Si
      substrate via a sol-gel composite method. The separation of the film from the
      substrate was achieved using a wet chemical method. The lifted-off PMN-35PT thick
      film exhibited good dielectric and ferroelectric properties. At 1 kHz, the
      dielectric constant and the dielectric loss were 3,326 and 0.037, respectively,
      while the remnant polarization was 30.0 uC/cm(2). A high frequency single element
      acoustic transducer fabricated with this film showed a bandwidth at -6 dB of
      63.6% at 110 MHz.

PMID- 21170159
TI  - The Moderating Effects of Pubertal Timing on the Longitudinal Associations
      Between Parent-Child Relationship Quality and Adolescent Substance Use.
AB  - This prospective, longitudinal study investigated the moderating role of pubertal
      timing on reciprocal links between adolescent appraisals of parent-child
      relationship quality and girls' (N=1335) and boys' (N=1203) cigarette and alcohol
      use across a twelve-month period. Reciprocal effects were found between parent
      child relations and on-time maturing boys and girls' cigarette and alcohol use,
      after estimating stability in these constructs across time. Parent-child
      relationship quality was associated with increased alcohol use twelve months
      later for early maturing girls. Cigarette and alcohol use were associated with
      increased problems in the parent-child relationship for late maturing girls. No
      off-time effects were observed for off-time maturing boys in the pathways between
      parent-child relationship quality and substance use. Pubertal timing moderated
      the pathway linking parent-child relationship quality with cigarette use one year
      later such that the association was stronger for late maturing girls compared to
      early and on-time maturing girls. The findings indicate interplay between the
      psychosocial aspects of maturation, family relationships and adolescent substance
      use and highlight possible gender-specific influences.

PMID- 21170160
TI  - Depressive Symptoms, Self-Reported Physical Functioning, and Identity in
      Community-Dwelling Older Adults.
AB  - OBJECTIVE: To examine the relationship between self-reported physical functioning
      and depressive symptoms by testing the mediation of identity processes in linking
      this relationship.  METHODS: Sixty-eight older adults (mean age= 74.4)
      participated in this cross-sectional study. Participants completed measures of
      physical functioning (Physical Symptoms Checklist), depressive symptoms (CESD-20)
      and identity processes (IES-G).  RESULTS: The relationship between physical
      functioning and depressive symptoms was partially mediated by sensitivity of
      older adults to feedback from experiences, the process known as identity
      accommodation (Whitbourne, Sneed, & Skultety, 2002).  CONCLUSION: Not only are
      physical changes relevant to negative psychological outcomes in later adulthood,
      but it is the interpretation of these changes that seems to have particular
      relevance for aging individuals. Though preliminary based on cross-sectional
      data, the findings suggest that examining individual differences in sensitivity
      to aging stereotypes may help identify factors related to depressive symptoms in
      later adulthood. Future research is needed to disentangle these interrelated
      concepts.

PMID- 21170161
TI  - Overt use of a tactile-kinesthetic strategy shifts to covert processing in
      rehabilitation of letter-by-letter reading.
AB  - BACKGROUND: Letter-by-letter readers identify each letter of the word they are
      reading serially in left to right order before recognizing the word. When their
      letter naming is also impaired, letter-by-letter reading is inaccurate and can
      render even single word reading very poor. Tactile and/or kinesthetic strategies
      have been reported to improve reading in these patients, but only under certain
      conditions or for a limited set of stimuli. AIMS: The primary aim of the current
      study was to determine whether a tactile/kinesthetic treatment could
      significantly improve reading specifically under normal reading conditions, i.e.
      reading untrained words presented in free vision and read without overt use of
      the strategy. METHODS #ENTITYSTARTX00026; PROCEDURES: Three chronic letter-by
      letter readers participated in a tactile/kinesthetic treatment aimed at first
      improving letter naming accuracy (phase 1) and then letter-by-letter reading
      speed (phase 2). In a multiple case series design, accuracy and speed of reading
      untrained words without overt use of the trained tactile/kinesthetic strategy was
      assessed before phase 1, after phase 1 and again after phase 2. OUTCOMES
      #ENTITYSTARTX00026; RESULTS: All three patients significantly improved both their
      speed and accuracy reading untrained words without overt use of the trained
      tactile/kinesthetic strategy. All three patients required the additional practice
      in phase 2 to achieve significant improvement. Treatment did not target sentence
      level reading, yet two of the three patients became so adept that they could read
      entire sentences. CONCLUSIONS: This study replicates previous findings on the
      efficacy of tactile/kinesthetic treatment for letter-by-letter readers with poor
      letter naming. It further demonstrates that this treatment can alter cognitive
      processing such that words never specifically trained can be read in free vision
      without overtly using the trained strategy. The data suggest that an important
      element in achieving this level of generalization is continuing training beyond
      the point of initial mastery (i.e. accurate letter naming).

PMID- 21170163
TI  - Education reform and the quality of kindergartens in Jordan.
AB  - The present study evaluates a major education reform in Jordan-the implementation
      of public kindergartens-and provides an example of how evaluation can be
      incorporated into education reform. In the context of education reform in Jordan,
      532 public kindergartens have been created over the last five years. A stratified
      random sample of kindergartens was selected to represent these new public
      kindergartens (n = 84) and previously existing private kindergartens (n = 23).
      Independent observers rated the quality of kindergarten environments in seven
      domains. Overall, 13% of public kindergarten environments were observed to be
      inadequate, 43% were of minimal quality, 43% were good, and 1% were excellent. In
      four of the seven domains, the quality of public kindergartens was significantly
      higher than the quality of private kindergartens; there were no significant
      differences in the other domains. Findings suggest the importance of continuing
      to implement high quality kindergartens in Jordan and of incorporating
      evaluations into education reform.

PMID- 21170162
TI  - The Multiple, Distinct Ways that Personality Contributes to Alcohol Use
      Disorders.
AB  - There is little question of whether personality is associated with problematic
      alcohol involvement (such as alcohol use disorders; AUDs); it clearly is.
      However, the question remains: how or why is personality related to risky
      drinking and AUDs? To address this question, theoretical models have been posited
      regarding the causal effects of personality on alcohol use and related problems.
      In this article, several of these models are summarized and reviewed. Future
      research directions are discussed, including possible frameworks that serve to
      integrate various models of the personality-AUD relation.

PMID- 21170164
TI  - Mechanics of Flexible Needles Robotically Steered through Soft Tissue.
AB  - The tip asymmetry of a bevel-tip needle results in the needle naturally bending
      when it is inserted into soft tissue. This enables robotic needle steering, which
      can be used in medical procedures to reach subsurface targets inaccessible by
      straight-line trajectories. However, accurate path planning and control of needle
      steering requires models of needle-tissue interaction. Previous kinematic models
      required empirical observations of each needle and tissue combination in order to
      fit model parameters. This study describes a mechanics-based model of robotic
      needle steering, which can be used to predict needle behavior and optimize system
      design based on fundamental mechanical and geometrical properties of the needle
      and tissue. We first present an analytical model for the loads developed at the
      tip, based on the geometry of the bevel edge and material properties of soft
      tissue simulants (gels). We then present a mechanics-based model that calculates
      the deflection of a bevel-tipped needle inserted through a soft elastic medium.
      The model design is guided by microscopic observations of needle-gel
      interactions. The energy-based formulation incorporates tissue-specific
      parameters, and the geometry and material properties of the needle. Simulation
      results follow similar trends (deflection and radius of curvature) to those
      observed in experimental studies of robotic needle insertion.

PMID- 21170165
TI  - Affairs of the Heart: Qualities of Adolescent Romantic Relationships and Sexual
      Behavior.
AB  - We know more about parent and peer influences than about the ways in which
      specific qualities of adolescent romantic relationships may influence sexual
      decision-making. Using data from the Toledo Adolescent Relationships Study, we
      focus on communication processes and emotional feelings, as well as more basic
      contours of adolescent romantic relationships, including power and influence
      dynamics. Controlling for traditional predictors and duration of the
      relationship, results suggest that subjectively experienced relationship
      qualities matter for understanding teens' sexual behavior choices. Further,
      findings indicate a similar effect of most relationship qualities on male and
      female reports of sexual behavior. However, influence and power dynamics within
      the relationship were not related to the likelihood that boys reported sexual
      intercourse in a focal relationship. In contrast, girls who perceived a more
      favorable power balance were less likely to report sexual intercourse than their
      female counterparts who perceived a less favorable power balance. Recognizing
      that the results capture reciprocal influence processes, longitudinal and
      qualitative data are used to further explore the complex nature of these
      associations.

PMID- 21170166
TI  - Effects of buprenorphine and hepatitis C on liver enzymes in adolescents and
      young adults.
AB  - OBJECTIVE: The purpose of this study was to explore changes in transaminase
      values associated with buprenorphine treatment and hepatitis C status among
      opioid dependent subjects aged 15-21. METHODS: 152 subjects seeking treatment for
      opioid dependence were randomized to 2-week detoxification with
      buprenorphine/naloxone (DETOX) or 12 weeks buprenorphine/naloxone (BUP). Liver
      chemistries including transaminases were obtained baseline and at 4, 8, and 12
      weeks. 111 patients had at least one set of transaminases during treatment and
      were included in analyses of treatment effects. RESULTS: Overall, 8/60 BUP
      participants vs. 12/51 DETOX participants had at least one elevated ALT value
      during follow-up (Chi-square n.s.). 5/60 BUP participants vs. 11/51 DETOX
      participants had at least one elevated AST value (Chi-square = 3.194, p = .048).
      Twenty-eight out of 152 participants were hepatitis C (HCV) positive at baseline,
      and 4 seroconverted within 12 weeks, 2 in each group. HCV status was
      significantly associated with transaminase abnormalities (p = .009 and p = .006
      for ALT an AST, respectively). HCV status had a strong effect on transaminase
      abnormalities among participants assigned to DETOX, but not among those assigned
      to BUP. CONCLUSIONS: No evidence was found for hepatotoxicity of buprenorphine in
      this exploratory analysis. HCV was present in a significant minority of
      participants and was a significant predictor of transaminase elevation. Results
      suggest that stabilization on buprenorphine may decrease the frequency of
      transaminase abnormalities associated with HCV in opioid dependent young people.
      The high rate of seroconversion underscores the importance of effective treatment
      and prevention.

PMID- 21170167
TI  - Behavioral and Emotional Strengths among Youth in Systems-of-Care and the Effect
      of Race/Ethnicity.
AB  - Behavioral and emotional strengths are important to consider when understanding
      youth mental health and treatment. This study examined the association between
      youth strengths and functional impairment, and whether this association is
      modified by race/ethnicity. Multinomial logistic regression models were used to
      estimate the effects of strengths on impairment, and examine whether race and
      ethnicity modified this relationship in 8,129 Caucasian, African American,
      Hispanic, and American Indian/Alaska Native youth, between 5 and 18 years of age.
      Results suggest that youth with average and above average strengths were less
      likely to have impairment compared to youth with below average strengths. Race
      and ethnicity modified this relationship in both expected and unexpected ways.
      Among youth with average and above average strengths, racial and ethnic minority
      youth appear to have more impairment than Caucasian youth. However, among youth
      with below average strengths, racial and ethnic minority youth have less
      impairment than Caucasian youth. Findings highlight the importance of
      incorporating strengths-based approaches in youth mental health treatment and the
      need for further research to understand the specific nature of strengths as it
      effects impairment across racial/ethnic groups. Implications and recommendations
      are discussed.

PMID- 21170168
TI  - Development and characterization of microsatellite markers in Sarracenia L.
      (pitcher plant) species.
AB  - Sarracenia species (pitcher plants) are carnivorous plants which obtain a portion
      of their nutrients from insects captured in the pitchers. Sarracenia species
      naturally hybridize with each other, and hybrid swarms have been identified. A
      number of the taxa within the genus are considered endangered. In order to
      facilitate evolutionary, ecological and conservation genetic analyses within the
      genus, we developed 25 microsatellite loci which show variability either within
      species or between species. Three S. purpurea populations were examined with 10
      primer sets which showed within population variability.

PMID- 21170169
TI  - Death concerns among individuals newly diagnosed with lung cancer.
AB  - Confronting the reality of death is an important challenge for individuals facing
      life-threatening illness such as lung cancer, the leading cause of cancer death.
      Few studies, however, document the nature of death-related concerns in
      individuals newly diagnosed with lung cancer. The aims of this exploratory study
      were to examine unsolicited death-related concerns among newly diagnosed
      individuals, and to determine if age, gender, marital status, stage of disease,
      type of treatment, presence of comorbid conditions, and veteran status were
      related to extent of death concerns. A mixed-method approach was used to examine
      death concerns in 73 individuals newly diagnosed with non-small cell lung cancer.
      Seven categories related to death were identified: psychological preparation,
      time left, impact, behavioral preparation, acceptance, cancer death experiences,
      and post-death. Stage of disease and veteran status were factors that were
      related to increased numbers of death-related content. Findings demonstrate that
      death concerns are varied, primarily negative, and are relevant to the person
      facing a new lung cancer diagnosis, thus highlighting the importance for health
      care providers to assess, discuss, and listen for death concerns in the acute
      care setting.

PMID- 21170170
TI  - A performance evaluation framework for association mining in spatial data.
AB  - The evaluation of the process of mining associations is an important and
      challenging problem in database systems and especially those that store critical
      data and are used for making critical decisions. Within the context of spatial
      databases we present an evaluation framework in which we use probability
      distributions to model spatial regions, and Bayesian networks to model the joint
      probability distribution and the structural relationships among spatial and non
      spatial predicates. We demonstrate the applicability of the proposed framework by
      evaluating representatives from two well-known approaches that are used for
      learning associations, i.e., dependency analysis (using statistical tests of
      independence) and Bayesian methods. By controlling the parameters of the
      framework we provide extensive comparative results of the performance of the two
      approaches. We obtain measures of recovery of known associations as a function of
      the number of samples used, the strength, number and type of associations in the
      model, the number of spatial predicates associated with a particular non-spatial
      predicate, the prior probabilities of spatial predicates, the conditional
      probabilities of the non-spatial predicates, the image registration error, and
      the parameters that control the sensitivity of the methods. In addition to
      performance we investigate the processing efficiency of the two approaches.

PMID- 21170171
TI  - Sources of Group and Individual Differences in Emerging Fraction Skills.
AB  - Results from a two year longitudinal study of 181 children from fourth through
      fifth grade are reported. Levels of growth in children's computation, word
      problem, and estimation skills using common fractions were predicted by working
      memory, attentive classroom behavior, conceptual knowledge about fractions, and
      simple arithmetic fluency. Comparisons of 55 participants identified as having
      mathematical difficulties to those without mathematical difficulties revealed
      that group differences in emerging fraction skills were consistently mediated by
      attentive classroom behavior and conceptual knowledge about fractions. Neither
      working memory nor arithmetic fluency mediated group differences in growth in
      fraction skills. It was also found that the development of basic fraction skills
      and conceptual knowledge are bidirectional in that conceptual knowledge exerted
      strong influences on all three types of basic fraction skills, and basic fraction
      skills exerted a more modest influence on subsequent conceptual knowledge.
      Results are discussed with reference to how the identification of potentially
      malleable student characteristics that contribute to the difficulties that some
      students have with fractions informs interventions and also will contribute to a
      future theoretical account concerning how domain general and domain specific
      factors influence the development of basic fraction skills.

PMID- 21170172
TI  - There Goes the Neighborhood: Lipreading and the Structure of the Mental Lexicon.
AB  - A central question in spoken word recognition research is whether words are
      recognized relationally, in the context of other words in the mental lexicon [1,
      2]. The current research evaluated metrics for measuring the influence of the
      mental lexicon on visually perceived (lipread) spoken word recognition. Lexical
      competition (the extent to which perceptually similar words influence recognition
      of a stimulus word) was quantified using metrics that are well-established in the
      literature, as well as a novel statistical method for calculating perceptual
      confusability, based on the Phi-square statistic.The Phi-square statistic proved
      an effective measure for assessing lexical competition and explained significant
      variance in visual spoken word recognition beyond that accounted for by
      traditional metrics. Because these values include the influence of all words in
      the lexicon (rather than only perceptually very similar words), it suggests that
      even perceptually distant words may receive some activation, and therefore
      provide competition, during spoken word recognition. This work supports and
      extends earlier research [3] that proposed a common recognition system underlying
      auditory and visual spoken word recognition and provides support for the use of
      the Phi-square statistic for quantifying lexical competition.

PMID- 21170173
TI  - Minimal formulation of joint motion for biomechanisms.
AB  - Biomechanical systems share many properties with mechanically engineered systems,
      and researchers have successfully employed mechanical engineering simulation
      software to investigate the mechanical behavior of diverse biological mechanisms,
      ranging from biomolecules to human joints. Unlike their man-made counterparts,
      however, biomechanisms rarely exhibit the simple, uncoupled, pure-axial motion
      that is engineered into mechanical joints such as sliders, pins, and ball-and
      socket joints. Current mechanical modeling software based on internal-coordinate
      multibody dynamics can formulate engineered joints directly in minimal
      coordinates, but requires additional coordinates restricted by constraints to
      model more complex motions. This approach can be inefficient, inaccurate, and
      difficult for biomechanists to customize. Since complex motion is the rule rather
      than the exception in biomechanisms, the benefits of minimal coordinate modeling
      are not fully realized in biomedical research. Here we introduce a practical
      implementation for empirically-defined internal-coordinate joints, which we call
      "mobilizers." A mobilizer encapsulates the observations, measurement frame, and
      modeling requirements into a hinge specification of the permissible-motion
      manifold for a minimal set of internal coordinates. Mobilizers support nonlinear
      mappings that are mathematically equivalent to constraint manifolds but have the
      advantages of fewer coordinates, no constraints, and exact representation of the
      biomechanical motion-space-the benefits long enjoyed for internal-coordinate
      models of mechanical joints. Hinge matrices within the mobilizer are easily
      specified by user-supplied functions, and provide a direct means of mapping
      permissible motion derived from empirical data. We present computational results
      showing substantial performance and accuracy gains for mobilizers versus
      equivalent joints implemented with constraints. Examples of mobilizers for joints
      from human biomechanics and molecular dynamics are given. All methods and
      examples were implemented in SimbodyTM-an open source multibody-dynamics solver
      available at https://Simtk.org.

PMID- 21170174
TI  - Dichloroacetate- and Trichloroacetate-Induced Modulation of Superoxide Dismutase,
      Catalase, and Glutathione Peroxidase Activities and Glutathione Level in the
      livers of Mice after Subacute and Subchronic exposure.
AB  - Dichloroacetate (DCA) and trichloroacetate (TCA) were previously found to induce
      various levels of oxidative stress in the hepatic tissues of mice after subacute
      and subchronic exposure. The cells are known to have several protective
      mechansims against production of oxidative stress by different xenobiotics. To
      assess the roles of the antioxidant enzymes and glutathione (GSH) in DCA- and TCA
      induced oxidative stress, groups of B6C3F1 mice were administered either DCA or
      TCA at doses of 7.7, 77, 154 and 410 mg/kg/day, by gavage for 4 weeks (4-W) and
      13 weeks (13-W), and superoxide dismutase (SOD) catalase (CAT) and glutathione
      peroxidase (GSH-Px) activities, as well as GSH were determined in the hepatic
      tissues. DCA at doses ranging between 7.7-410, and 7.7-77 mg/kg/day, given for 4
      W and 13-W, respectively, resulted in either suppression or no change in SOD, CAT
      and GSH-Px activities, but doses of 154-410 mg DCA/kg/day administered for 13-W
      were found to result in significant induction of the three enzyme activities. TCA
      administration on the other hand, resulted in increases in SOD and CAT
      activities, and suppression of GSH-Px activity in both periods. Except for the
      DCA doses of 77-154 mg/kg/day administered for 13-W that resulted in significant
      reduction in GSH levels, all other DCA, as well as TCA treatments produced no
      changes in GSH. Since these enzymes are involved in the detoxification of the
      reactive oxygen species (ROS), superoxide anion (SA) and H(2)O(2), it is
      concluded that SA is the main contributor to DCA-induced oxidative stress while
      both ROS contribute to that of TCA. The increases in the enzyme activities
      associated with 154-410 mg DCA/kg/day in the 13-W period suggest their role as
      protective mechanisms contributing to the survival of cells modified in response
      to those treatments.

PMID- 21170175
TI  - Investigating and Annotating the Role of Citation in Biomedical Full-Text
      Articles.
AB  - Citations are ubiquitous in scientific articles and play important roles for
      representing the semantic content of a full-text biomedical article. In this
      work, we manually examined full-text biomedical articles to analyze the semantic
      content of citations in full-text biomedical articles. After developing a
      citation relation schema and annotation guideline, our pilot annotation results
      show an overall agreement of 0.71, and here we report on the research challenges
      and the lessons we've learned while trying to overcome them. Our work is a first
      step toward automatic citation classification in full-text biomedical articles,
      which may contribute to many text mining tasks, including information retrieval,
      extraction, summarization, and question answering.

PMID- 21170176
TI  - The Impact of Stressful Life Events on Alcohol Relapse: Findings from the
      Collaborative Longitudinal Personality Disorders Study.
AB  - Alcohol relapse is impacted by a variety of environmental, interpersonal, and
      intrapersonal factors. We examined the interaction between stressful life events,
      personality disorder subtype, and alcohol relapse among individuals enrolled in
      the Collaborative Longitudinal Personality Disorders Study (CLPS). Negative life
      events predicted relapse in all subjects. In individuals with a history of an
      alcohol use disorder prior to study entry, positive life events also predicted
      alcohol relapse. Individuals with Antisocial Personality Disorder (ASPD) were
      found to be twice as likely to relapse in response to life stressors compared to
      individuals with Obsessive-Compulsive Personality Disorder (OCPD), who were half
      as likely to relapse in response to life stressors. Further analysis revealed
      that individuals with OCPD and no history of an alcohol use disorder were almost
      10 times more likely to relapse in the face of a stressful romantic problem,
      while those with ASPD and a history of an alcohol use disorder were six times
      more likely to relapse in response to a stressful financial event. These findings
      have implications for both the assessment and the treatment of individuals who
      present with co-morbid personality and alcohol use disorders.

PMID- 21170177
TI  - A method for the determination of the two-dimensional MTF of digital radiography
      systems using only the noise response.
AB  - We present a new method that enables the determination of the two-dimensional MTF
      of digital radiography systems using the noise response measured from flat-field
      images. Unlike commonly-used methods that measure the one-dimensional MTF, this
      new method does not require precision-made test-objects (slits/edges) or precise
      tool alignment. Although standard methods are dependent upon data processing that
      can result in inaccuracies and inconsistencies, this method based on the
      intrinsic noise response of the imager is highly accurate and less susceptible to
      such problems. A cascaded-linear-systems analysis was used to derive an exact
      relationship between the noise power spectrum (NPS) and the presampled MTF of a
      generalized detector system. The NPS was then used to determine the two
      dimensional MTF for three systems: a simulated detector in which the "true" MTF
      was known exactly, a commercial indirect flat-panel detector (FPD), and a new
      solid-state x-ray image intensifier (SSXII). For the simulated detector,
      excellent agreement was observed between the "true" MTF and that determined using
      the noise response method, with an averaged deviation of 0.3%. The FPD MTF was
      shown to increase on the diagonals and was measured at 2.5 cycles/mm to be
      0.086+/-0.007, 0.12+/-0.01, and 0.087+/-0.007 at 0, 45, and 90 degrees ,
      respectively. No statistically significant variation was observed for the SSXII
      as a function of angle. Measuring the two-dimensional MTF should lead to more
      accurate characterization of the detector resolution response, incorporating any
      potential non-isotropy which may result from the physical characteristics of the
      sensor, including the active-area shape of the pixel array.

PMID- 21170178
TI  - HIV/AIDS Risk Reduction Intervention for Women who have Experienced Intimate
      Partner Violence.
AB  - A growing body of literature highlights the association between women who have
      experienced intimate partner abuse (IPA) and their heightened risk for HIV/AIDS
      (human immune deficiency syndrome/ acquired immune deficiency syndrome)
      infection. Finding HIV risk reduction strategies that are contextually relevant
      for this population is an important public policy priority. This qualitative
      study researched women who have experienced intimate partner abuse in order to
      develop a HIV/AIDS risk reduction intervention unique to their circumstances.
      This pilot study explored the critical components of such an intervention among a
      racially/ethnically stratified (African-American, Mexican-American and Anglo)
      sample of women (n=43) who have experienced IPA. Focus groups were conducted and
      transcribed, and a content analysis was used to identify major themes. In all
      five focus groups, participants viewed the research as interesting, good,
      beneficial, and/or important based on their perceptions of risk for infection.
      Respondents felt that they knew of ways to protect themselves from infection in
      non-abusive relationships; however, acknowledged the difficulties of doing so
      given the context of their abusive relationships. Examining the racial/ethnic
      differences across focus groups showed that the language used by women is quite
      variable. The ways in which survivors define rape, sexual abuse, and their own
      experiences are all unique; however, their actual experiences have many
      similarities. Discussed at length are the topics participants shared as critical
      in informing the design of an intervention and the relevance of the findings to
      social work clinical practice is explained.

PMID- 21170179
TI  - Making a difference with evidence.
AB  - In this column, the editor of The Journal of Perinatal Education describes how,
      despite the many challenges confronting childbirth educators today in our complex
      health-care environment, there is still a ray of hope that committed individuals
      translating evidence into practice can make a difference. The editor also
      describes the contents of this special issue, which celebrates the 50th
      anniversary of Lamaze International and offers a broad range of resources,
      research, and inspiration for childbirth educators in their efforts to promote
      natural, safe, and healthy birth.

PMID- 21170180
TI  - Social Media, Power, and the Future of VBAC.
AB  - The Internet has been called a disruptive technology because it has shifted power
      and altered the economics of doing business, whether that business is selling
      books or providing health care. Social media have accelerated the pace of
      disruption by enabling interactive information sharing and blurring the lines
      between the "producers" and "consumers" of knowledge, goods, and services. In the
      wake of the National Institutes of Health Consensus Development Conference on
      Vaginal Birth After Cesarean (VBAC) and major national recommendations for
      maternity care reform, activated, engaged consumers face an unprecedented
      opportunity to drive meaningful changes in VBAC access and safety. This article
      examines the role of social networks in informing women about VBAC, producing low
      cost, accessible decision aids, and enabling multi-stakeholder collaborations
      toward workable solutions that remove barriers women face in accessing VBAC.

PMID- 21170181
TI  - A concern on in-phantom photon energy response of luminescence dosimeters for
      clinical applications.

PMID- 21170182
TI  - Implementation and validation of a commercial portal dosimetry software for
      intensity-modulated radiation therapy pre-treatment verification.
AB  - Electronic portal imaging devices (EPIDs) are extensively used for obtaining
      dosimetric information of pre-treatment field verification and in-vivo dosimetry
      for intensity-modulated radiotherapy (IMRT). In the present study, we have
      implemented the newly developed portal dosimetry software using independent dose
      prediction algorithm EPIDose(TM) and evaluated this new tool for the pre
      treatment IMRT plan quality assurance of Whole Pelvis with Simultaneous
      Integrated Boost (WP-SIB-IMRT) of prostate cases by comparing with routine two
      dimensional (2D) array detector system (MapCHECK(TM)). We have investigated 104
      split fields using gamma -distributions in terms of predefined gamma frequency
      parameters. The mean gamma values are found to be 0.42 (SD: 0.06) and 0.44 (SD:
      0.06) for the EPIDose and MapCHECK(TM), respectively. The average gamma? for
      EPIDose and MapCHECK(TM) are found as 0.51 (SD: 0.06) and 0.53 (SD: 0.07),
      respectively. Furthermore, the percentage of points with gamma < 1, gamma < 1.5,
      and gamma > 2 are 97.4%, 99.3%, and 0.56%, respectively for EPIDose and 96.4%,
      99.0% and 0.62% for MapCHECK(TM). Based on our results obtained with EPIDose and
      strong agreement with MapCHECK(TM), we may conclude that the EPIDose portal
      dosimetry system has been successfully implemented and validated with our routine
      2D array detector.

PMID- 21170183
TI  - Dose-volume histogram quality assurance for linac-based treatment planning
      systems.
AB  - Dose-volume histograms provide key information to radiation oncologists when they
      assess the adequacy of a patient treatment plan in radiation therapy. It is
      important therefore that all clinically relevant data be accurate. In this
      article we present the first quality assurance routine involving a direct
      comparison of planning system results with the results obtained from independent
      hand calculations. Given a known three-dimensional (3-D) structure such as a
      parallelepiped, a simple beam arrangement, and known physics beam data, a time
      efficient and reproducible method for verifying the accuracy of volumetric
      statistics (DVH) from a radiation therapy treatment planning system (TPS) can be
      employed rapidly, satisfying the QA requirements for (TPS) commissioning,
      upgrades, and annual checks. Using this method, the maximum disagreement was only
      1.7% for 6 MV and 1.3% for 18 MV photon energies. The average accuracy was within
      0.6% for 6 MV and 0.4% for 18 MV for all depth-dose results. A 2% disagreement
      was observed with the treatment planning system DVH from defined volume
      comparison to the known structure dimensions.

PMID- 21170185
TI  - Electron beam characteristics at extended source-to-surface distances for
      irregular cut-outs.
AB  - Electron beam therapy is widely used in the management of cancers. The rapid dose
      fall-off and the short range of an electron beam enable the treatment of lesions
      close to the surface, while sparing the underlying tissues. In an extended source
      to-surface (SSD) treatment with irregular field sizes defined by cerrobend
      cutouts, underdosage of the lateral tissue may occur due to reduced beam flatness
      and uniformity. To study the changes in the beam characteristics, the depth dose,
      beam profile, and isodose distributions were measured at different SSDs for
      regular 10 * 10 cm(2) and 15 * 15 cm(2) cone, and for irregular cutouts of field
      size 6.5 * 9 cm(2) and 11.5 * 15 cm(2) for beam energies ranging from 6 to 20
      MeV. The PDD, beam flatness, symmetry and uniformity index were compared. For
      lower energy (6 MeV), there was no change in the depth of maximum dose (R100) as
      SSD increased, but for higher energy (20 MeV), the R(100) depth increased from 2
      cm to 3 cm as SSD increased. This shows that as SSD increases there is an
      increase in the depth of the maximum dose for higher energy beams. There is a +7
      mm shift in the R(100) depth when compared with regular and irregular field
      sizes. The symmetry was found to be within limits for all the field sizes as the
      treatment distance extended as per International Electro technical Commision
      (IEC) protocol. There was a loss of beam flatness for irregular fields and it was
      more pronounced for lower energies as compared with higher energies, so that the
      clinically useful isodose level (80% and 90%) width decreases with increase in
      SSD. This suggests that target coverage at extended SSD with irregular cut-outs
      may be inadequate unless relatively large fields are used.

PMID- 21170184
TI  - Effect of various physical parameters on surface and build-up dose for 15-MV X
      rays.
AB  - The purpose of this study was to find out the effect of various physical
      parameters on the skin and build-up doses of 15-MV photon beams. The effects of
      field dimensions, acrylic shadow tray, focus to-skin distance (FSD) on surface
      and buildup dose were determined for open, motorized 60 degrees  wedge (MW) and
      blocked fields. A 'Markus' plane parallel plate chamber was used for these
      measurements in an Elekta (6-15MV) linear accelerator. The surface dose for MW
      fields was lower than the dose for an open field, but the trend reversed for
      large fields and higher degree wedges. With the use of an acrylic shadow tray,
      the surface dose increased for all field sizes, but the increase was dominant for
      large fields. The surface dose for blocked fields was lower than the dose for
      open fields. The percentage depth dose of 10 * 10 cm(2) field at surface (PDD(0))
      for open beam were 13.89%, 11.71%, and 10.74% at 80 cm, 100 cm, and 120 cm FSD,
      respectively. The blocking tray increased PDD(0) of 10 * 10 cm(2) field to
      26.29%, 14.01%, and 11.53%, while the motorized 60 degrees  wedge decreased
      PDD(0) to 11.32%, 9.7%, and 8.9 % at these FSDs. The maximum PDD difference seen
      at surface (i.e., skin) for 5 * 5 cm(2), 15 * 15 cm(2), and 30 * 30 cm(2) are
      0.5%, 4.6%, and 5.6% for open field and 0.9%, 4.7%, and 7.2% for motorized 60
      degrees  wedge field, when FSDs varied from 80 cm to 120 cm. The maximum PDD
      difference seen at surface for 5 * 5 cm(2), 15 * 15 cm(2), and 30 * 30 cm(2)
      fields are 5.6%, 22.8%, and 29.6%, respectively, for a 1.0-cm perspex-blocking
      tray as the FSD is changed. The maximum PDD difference was seen at the surface
      (i.e., skin) and this decreased with increasing depth.

PMID- 21170186
TI  - Experimental determination of the weighting factor for the energy window
      subtraction-based downscatter correction for I-123 in brain SPECT studies.
AB  - Correction for downscatter in I-123 SPECT can be performed by the subtraction of
      a secondary energy window from the main window, as in the triple-energy window
      method. This is potentially noise sensitive. For studies with limited amount of
      counts (e.g. dynamic studies), a broad subtraction window with identical width is
      preferred. This secondary window needs to be weighted with a factor higher than
      one, due to a broad backscatter peak from high-energy photons appearing at 172
      keV. Spatial dependency and the numerical value of this weighting factor and the
      image contrast improvement of this correction were investigated in this study.
      Energy windows with a width of 32 keV were centered at 159 keV and 200 keV. The
      weighting factor was measured both with an I-123 point source and in a dopamine
      transporter brain SPECT study in 10 human subjects (5 healthy subjects and 5
      patients) by minimizing the background outside the head. Weighting factors ranged
      from 1.11 to 1.13 for the point source and from 1.16 to 1.18 for human subjects.
      Point source measurements revealed no position dependence. After correction, the
      measured specific binding ratio (image contrast) increased significantly for
      healthy subjects, typically by more than 20%, while the background counts outside
      of all subjects were effectively removed. A weighting factor of 1.1-1.2 can be
      applied in clinical practice. This correction effectively removes downscatter and
      significantly improves image contrast inside the brain.

PMID- 21170187
TI  - Automatic and manual image fusion of In-pentetreotide SPECT and diagnostic CT in
      neuroendocrine tumor imaging - An evaluation.
AB  - In the clinical diagnosis of neuroendocrine tumors (NET), the results of
      examinations, such as high-resolution computed tomography (CT) and single photon
      computerized tomography (SPECT), have conventionally been interpreted separately.
      The aim of the present study was to evaluate Hermes MultimodalityTM 5.0 H Image
      Fusion software-based automatic and manual image fusion of SPECT and CT for the
      localization of NET lesions. Out of 34 NET patients who were examined by means of
      somatostatin receptor scintigraphy (SRS) with 111In- pentetreotide along with
      SPECT, 22 patients had a CT examination of the abdomen, which was used in the
      fusion analysis. SPECT and CT data were fused using software with a registration
      algorithm based on normalized mutual information. The criteria for acceptable
      fusion were established at a maximum cranial or caudal dislocation of 25 mm
      between the images and at a reasonable consensus (in order of less than 1 cm)
      between outline of the reference organs. The automatic fusion was acceptable in
      13 of the 22 examinations, whereas 9 fusions were not. However all the 22
      examinations were acceptable at the manual fusion. The result of automatic fusion
      was better when the slice thickness of 5 mm was applied at CT examination, when
      the number of slices was below 100 in CT data and when both examinations included
      uptakes of pathological lesions. Retrospective manual image fusion of SPECT and
      CT is a relatively inexpensive but reliable method to be used in NET imaging.
      Automatic image fusion with specified software of SPECT and CT acts better when
      the number of CT slices is reduced to the SPECT volume and when corresponding
      pathological lesions appear at both SPECT and CT examinations.

PMID- 21170188
TI  - Radiological safety status and quality assurance audit of medical X-ray
      diagnostic installations in India.
AB  - We conducted a radiological safety and quality assurance (QA) audit of 118
      medical X-ray diagnostic machines installed in 45 major hospitals in India. The
      main objective of the audit was to verify compliance with the regulatory
      requirements stipulated by the national regulatory body. The audit mainly covered
      accuracy check of accelerating potential (kVp), linearity of tube current (mA
      station) and timer, congruence of radiation and optical field, and total
      filtration; in addition, we also reviewed medical X-ray diagnostic installations
      with reference to room layout of X-ray machines and conduct of radiological
      protection survey. A QA kit consisting of a kVp Test-O-Meter (ToM) (Model RAD/FLU
      9001), dose Test-O-Meter (ToM) (Model 6001), ionization chamber-based radiation
      survey meter model Gun Monitor and other standard accessories were used for the
      required measurements. The important areas where there was noncompliance with the
      national safety code were: inaccuracy of kVp calibration (23%), lack of
      congruence of radiation and optical field (23%), nonlinearity of mA station (16%)
      and timer (9%), improper collimator/diaphragm (19.6%), faulty adjustor knob for
      alignment of field size (4%), nonavailability of warning light (red light) at the
      entrance of the X-ray room (29%), and use of mobile protective barriers without
      lead glass viewing window (14%). The present study on the radiological safety
      status of diagnostic X-ray installations may be a reasonably good representation
      of the situation in the country as a whole. The study contributes significantly
      to the improvement of radiological safety by the way of the steps already taken
      and by providing a vital feed back to the national regulatory body.

PMID- 21170189
TI  - Spatial distribution of gamma radiation levels in surface soils from Jaduguda
      uranium mineralization zone, Jharkhand, India, using gamma-ray spectrometry, and
      determination of outdoor dose to the population.
AB  - The concentrations of natural radionuclides in surface soil samples around
      selected villages of Jaduguda were investigated and compared with the
      radioactivity level in the region. Concentrations of (238)U, (232)Th, and (40)K
      were determined by a gamma ray spectrometer using the HPGe detector with 50%
      relative efficiency, and the radiation dose to the local population was
      estimated. The average estimated activity concentrations of (238)U, (232)Th, and
      (40)K in the surface soil were 53.8, 44.2 and 464.2 Bq kg(-1) respectively. The
      average absorbed dose rate in the study area was estimated to be 72.5 nGy h-1,
      where as the annual effective dose to the population was 0.09 mSv y-1. A
      correlation analysis was made between measured dose rate and individual
      radionuclides, in order to delineate the contribution of the respective nuclides
      towards dose rate. The radio-elemental concentrations of uranium, thorium and
      potassium estimated for the soils, in the study area, indicated the enrichment of
      uranium series nuclide. The results of the present study were subsequently
      compared with international and national recommended values.

PMID- 21170190
TI  - Indoor radon survey in a university campus of Nigeria.
AB  - CR-39 tracketch detectors were used for the measurement of (222)Rn concentration
      in 24 offices in Nigeria's oldest university campus in order to estimate the
      effective dose to the occupants from (222)Rn and its progeny. The dosimetric
      measurements were made over a period of 3 months. Questionnaires were distributed
      and analyzed. The radon concentration ranged from 157 to 495 Bq/m(3), with an
      arithmetic mean and standard deviation of 293.3 and 79.6 Bq/ m(3), respectively.
      The effective dose to the workers was estimated and this varied from 0.99 to 3.12
      mSv/ y, with a mean of 1.85 mSv/y. The radon concentrations were found to be
      within the reference levels of ICRP.

PMID- 21170191
TI  - Indian Association of Pediatric Surgeons-Presidential Address delivered at 36
      annual conference, New Delhi, October 2010.

PMID- 21170192
TI  - The role of nitric oxide in portal hypertension caused by extrahepatic portal
      vein obstruction.
AB  - AIMS: Nitric oxide (NO) in peripheral venous blood has been shown to be elevated
      in experimental portal hypertension. This study aims to determine the serum NO
      levels in patients with extrahepatic portal venous hypertension (EHPVO) pre- and
      postoperatively and to analyze whether these can serve as a reliable and early
      indicator of shunt blockage or malfunction. MATERIALS AND METHODS: During the
      period 2006-2010, 48 children with EHPVO were included in this prospective study;
      40 underwent porto-systemic shunt and eight underwent splenectomy with
      devascularization. NO was evaluated preoperatively, 14 days after surgery, at 3
      months and then 6 monthly thereafter. The median follow-up duration was 21
      months. Shunt patency was confirmed with Doppler and computed tomography
      portography. Forty-eight age-matched children with hypospadias served as
      controls. RESULTS: NO was higher in EHPVO patients as compared with controls
      (43.16 +/- 16.27 vs. 5.76 +/- 2.62 MUmol/l) (P = 0.0001). There was a significant
      decline in the NO levels (4.64 +/- 3.18 MUmol/l) following shunt surgery (P =
      0.0001), and it continued to remain low till the shunt was patent. A shunt block
      was indicated by rising NO levels in all five patients. The devascularization
      group also demonstrated a significant decline in the NO levels (27.06 +/- 3.56
      MUmol/l) (P = 0.002), but it was less as compared with the shunted patients. The
      decline in the portal pressure after shunt surgery was found to correlate with
      the decline in the serum NO levels. CONCLUSIONS: The blood levels of NO can be
      used in the diagnosis of portal hypertension, and are useful for monitoring the
      patency of the shunt.

PMID- 21170193
TI  - Pediatric laparoscopy: Facts and factitious claims.
AB  - BACKGROUND: Pediatric laparoscopy (LS) is claimed to be superior to open surgery
      (OS). This review questions the scientific veracity of this assertion by
      systematic analysis of published evidences comparing LS versus OS in infants and
      children. MATERIALS AND METHODS: Search of PubMed data base and the available
      literature on pediatric LS is analyzed. RESULTS: One hundred and eight articles
      out of a total of 426 papers were studied in detail. CONCLUSIONS: High quality
      evidences indicate that LS is, at the best, as invasive as OS; and is at the
      worst, more invasive than conventional surgery. There are no high quality
      evidences to suggest that LS is minimally invasive, economically profitable and
      is associated with fewer complications than OS. Evidences are equally distributed
      for and against the benefits of LS regarding postoperative pain. Proof of
      cosmetic superiority of LS or otherwise is not available. The author concludes
      that pediatric laparoscopy, at the best, is simply comparable to laparotomy and
      its superiority over the latter could not be sustained on the basis of available
      scientific evidences. Benefits of laparoscopy appear to recede with younger age.
      Concerns are raised on the quick adoption, undue promotion and frequent misuse of
      laparoscopy in children.

PMID- 21170194
TI  - Pediatric foreign body aspiration: How much does our community know?
AB  - AIMS: Foreign body aspiration (FBA) is one of the main causes of accidental death
      in childhood. This study was designed to evaluate the level of awareness of FBA
      and its resultant dangers in the community. MATERIALS AND METHODS: Sixty-three
      primary caregivers were interviewed about their awareness of FBA, its attendant
      dangers, preventive measures taken, and how will they take care of a child in the
      event of a FBA according to an agreed protocol. RESULTS: Awareness levels about
      FBA were abysmally low in the population that was studied. Twenty-five percentage
      of the study population had not heard about this condition, and 46% could not
      recognize a FBA if it happened. Also, 76% of the study group did not know about
      the attendant dangers of this condition. CONCLUSIONS: There is a dire need to
      spread awareness about both prevention and treatment of this morbid condition.
      Health care professionals need to increase their efforts to spread more knowledge
      in the community about FBA.

PMID- 21170195
TI  - Neonatal carrier: An easy to make alternative device to costly transport
      chambers.
AB  - The transport of sick neonates to the surgical centers or transportation within
      the center is an essential requirement of neonatal surgery. Neonatal transport
      incubators are costly, space occupying, and are not available at many places in
      the developing countries. We report here a cheap yet effective and easy to make,
      alternate neonatal carrier device.

PMID- 21170196
TI  - Partial duplication of vas deferens: How important is it?
AB  - This study reports a 1-year-old boy with unilateral partial duplication of vas
      deferens, diagnosed during surgery for undescended testis. Pediatric surgeons
      need to be aware of this kind of anomaly in order to avoid injury to this vital
      structure.

PMID- 21170197
TI  - Currarino's triad: Intraoperative ultrasound image-guided surgery.
AB  - This is a report on the use of transperineal intraoperative ultrasound imaging in
      a case of Currarino's triad for the first time in the literature.

PMID- 21170198
TI  - Acute acalculous cholecystitis causing gall bladder perforation in children.
AB  - We report two cases of children who presented with acute abdomen due to gall
      bladder perforation and biliary peritonitis. Cholecystectomy with peritoneal
      lavage proved curative.

PMID- 21170199
TI  - Pedicled omental split skin graft: A novel method for reconstruction of full
      thickness abdominal wall defect.
AB  - Although rare in children, aggressive fibromatosis or desmoid tumors require wide
      surgical excision for durable relief. The resultant defect poses many challenges
      for reconstruction. The authors report reconstruction of such a wound using a
      pedicled omental split skin graft, which resulted from the excision of a locally
      recurrent desmoid tumor.

PMID- 21170200
TI  - Lumbotomy for multicystic dysplastic kidney: A trap for the unwary.
AB  - This is a report of a case of multicystic dysplastic half of a horseshoe kidney
      (HSK) at surgery for multicystic kidney. During the surgery, through a lumbotomy
      approach, there was inadvertent injury to a lower polar artery and the pelvis of
      the normal contralateral half of the HSK, leading to a stormy postoperative
      course. This report emphasizes the need for accurate preoperative diagnosis
      before embarking on a lumbotomy, and also reviews the entity of multicystic
      dysplasia in one half of a HSK.

PMID- 21170201
TI  - Gastrointestinal stromal tumor: Role of surgery and immunotherapy.
AB  - Report of a gastrointestinal stromal tumor in an 11-year-old girl who presented
      with a large lump in the upper abdomen. After complete surgical excision and
      histopathology, postoperative immunotherapy with imatinib led to an excellent
      outcome and a tumor-free survival of 3 years.

PMID- 21170202
TI  - [Not Available].

PMID- 21170203
TI  - Four new approaches for validation of Ayurvedic herbal drugs.

PMID- 21170204
TI  - Usage trends for memory and vitality-enhancing medicines: A
      pharmacoepidemiological study involving pharmacists of the Gujarat region.
AB  - OBJECTIVE: The aim of the study was to explore the trends and rationale of use of
      memory and vitality-enhancing medicines (MVEM) in the Gujarat region. MATERIALS
      AND METHODS: A prospective pharmacoepidemiological study involving pharmacists of
      Gujarat region was carried out in the year 2005. Pharmacists (n = 351) working in
      general and Ayurvedic medical stores were selected from 12 districts of Gujarat
      region. The pharmacists were explained about the objective of the study and were
      given a pretested, validated questionnaire. OUTCOME MEASURES: The questionnaire
      included the questions regarding herbal MVEM used most commonly, percentage sale
      of herbal MVEM - sold with or without prescriptions - age group of patients and
      professional groups who used these drugs most commonly. RESULTS: The number of
      individuals using MVEM was highest in the age group of 11-20 years (17.54%),
      followed by the 21-40 years group (17.12%), supporting the results that the
      professional group of students (17.29%) and the persons of business or service
      class (15.29%) are the highest users of these medicines. Evaluation of various
      constituents in the marketed polyherbal MVEM revealed that Brahmi (Bacopa
      monniera), Shankhpushpi (Evolvulus alsinoides), Ashwangandha (Withania
      somnifera), Jatamansi (Nardostychos jatamansi), Vacha (Acorus calamus) and Amla
      (Phyllanthus emblica) were the common ingredients in the polyherbal preparations.
      CONCLUSIONS: This study highlights commonly used Ayurvedic medicines that can be
      explored for safely enhancing memory and vitality performance. Hence, detailed
      and scientifically designed research on these drugs would help to identify safe
      and effective drugs for enhancing the same.

PMID- 21170205
TI  - Effects of Withania somnifera (Ashwagandha) and Terminalia arjuna (Arjuna) on
      physical performance and cardiorespiratory endurance in healthy young adults.
AB  - INTRODUCTION: Several medicinal plants have been described to be beneficial for
      cardiac ailments in Ayurveda like Ashwagandha and Arjuna. Ashwagandha-categorised
      as Rasayanas, and described to promote health and longevity and Arjuna primarily
      for heart ailments. coronary artery disease, heart failure, hypercholesterolemia,
      anginal pain and can be considered as a useful drug for coronary artery disease,
      hypertension and ischemic cardiomyopathy. OBJECTIVE: There are no scientific
      clinical studies showing effect of both these drugs on exercise performance after
      regular administration when given as supplements The present study was therefore
      designed and performed to assess the effects of Withania somnifera (Ashwagandha)
      and Terminalia arjuna (Arjuna) individually and as a combination on maximum
      velocity, average absolute and relative Power, balance, maximum oxygen
      consumption (VO2 max) and blood pressure in humans. MATERIALS AND METHODS: Forty
      normal healthy. Subjects (either sex, mean age 20.6 +/- 2.5yrs and mean Body Mass
      Index 21.9 +/- 2.2) were recruited after written informed consent was obtained.
      Institutional Ethics Committee permission was also obtained. Thirty participants
      were assigned to experimental group of which 10 received standardized root
      extracts of Withania somnifera, 10 received standardized bark extract of
      Terminalia arjuna and the rest of the 10 received standardized root extract of
      Withania somnifera in addition to bark extract of Terminalia arjuna both. Both
      the drugs were given in the form of capsules (dosage 500mg/day for both the
      drugs). Ten participants received placebo (capsules filled with flour). All the
      subjects continued the regimen for 8 weeks. All variables were assessed before
      and after the course of drug administration OBSERVATIONS: Our study showed that
      Withania somnifera increased velocity, power and VO2 max whereas Terminalia
      arjuna increased VO2 max and lowered resting systolic blood pressure. When given
      in combination, the improvement was seen in all parameters except balance and
      diastolic blood pressure. CONCLUSION: Withania somnifera may therefore be useful
      for generalized weakness and to improve speed and lower limb muscular strength
      and neuro-muscular co-ordination. Terminalia arjuna may prove useful to improve
      cardio-vascular endurance and lowering systolic blood pressure. Both drugs appear
      to be safe for young adults when given for mentioned dosage and duration.

PMID- 21170207
TI  - Antioxidant and hypolipidemic activity of Kumbhajatu in hypercholesterolemic
      rats.
AB  - OBJECTIVE: To study the efficacy of Kumbhajatu in reducing the cholesterol levels
      and as an antioxidant in hypercholesterolemic rats. MATERIALS AND METHODS:
      Hypercholesterolemia was induced in normal rats by including 2% w/w cholesterol,
      1% w/w sodium cholate and 2.5% w/w coconut oil in the normal diet. Powdered form
      of Kumbhajatu was administered as feed supplement at 250 and 500 mg/kg dose
      levels to the hypercholesterolemic rats. Plasma lipid profile, hepatic superoxide
      dismutase (SOD) activity, catalase activity, reduced glutathione and extent of
      lipid peroxidation in the form of malondialdehyde were estimated using standard
      methods. RESULTS: Feed supplementation with 250 and 500 mg/kg of Kumbhajatu
      resulted in a significant decline in plasma lipid profiles. The feed
      supplementation increased the concentration of catalase, SOD, glutathione and HDL
      c significantly in both the experimental groups (250 and 500 mg/kg). On the other
      hand, the concentration of malondialdehyde, cholesterol, triglycerides, LDL-c and
      VLDL in these groups (250 and 500 mg/kg) were decreased significantly.
      CONCLUSION: The present study demonstrates that addition of Kumbhajatu powder at
      250 and 500 mg/kg level as a feed supplement reduces the plasma lipid levels and
      also decreases lipid peroxidation.

PMID- 21170206
TI  - Mahayograj guggulu: Heavy metal estimation and safety studies.
AB  - OBJECTIVE: This study was conducted to estimate the heavy metal profile and
      determine the safety of Mahayograj guggulu, an Ayurvedic herbo-mineral
      preparation. DESIGN: Mahayograj guggulu, manufactured by Shree Baidynath Ayurved
      Bhawan Pvt. Ltd., Gwalior Road, Jhansi - 284 003 (of batch number-07 and
      manufacturing date October 2004) was procured from the local market. Heavy metal
      concentrations were measured using an atomic absorption spectrophotometer. A
      total of 40 Charles Foster strain albino rats of either sex with an average body
      weight of 160-250 g were divided into four groups (Groups I, II, III and IV),
      with 10 animals in each group. Group I served as the control, while Group II, III
      and IV rats received Mahayograj guggulu at a dose of 54 (dose equivalent to human
      therapeutic dose), 270 (five-times the dose equivalent to the human therapeutic
      dose) and 540 (10-times the dose equivalent to human therapeutic dose) mg/kg,
      p.o. for 120 days. The effect of drug administration was noted on the ponderal,
      biochemical, hematological and histopathological parameters. In addition, urine
      examination was also carried out. At the end of the study, only six rats per
      group were sacrificed as per the IAEC advice. RESULTS: Mahayograj guggulu was
      found to be safe at all dose levels tested. No significant behavioral changes
      were noted in any of the groups studied. The effect on food and water consumption
      and fecal and urine output remained unaffected in all groups during the study
      period. No major alterations were observed in hematology, serum biochemistry,
      necropsy and histopathology at the therapeutically advocated dose level. Heavy
      metal content measurement indicated levels of 25.8 ug/g for lead, 0.07 ug/g for
      mercury and 5.19 ug/g for arsenic. CONCLUSIONS: The test drug is well tolerated
      as no changes of a serious nature could be observed in any of the parameters
      assessed.

PMID- 21170208
TI  - Antihyperglycemic activity of Tectona grandis Linn. bark extract on alloxan
      induced diabetes in rats.
AB  - Tectona Grandis Linn.(saag - tick wood), an indigenous medicinal plant, has a
      folk reputation among the Indian herbs as a hypoglycemic agent. The present study
      was carried out to evaluate the anti-hyperglycemic effect of T. grandis Linn.
      bark extract in control and alloxan-diabetic rats. Oral administration of the
      bark suspension of T. grandis (2.5 and 5 g/kg body wt.) for 30 days resulted in a
      significant reduction in blood glucose (from 250 +/- 6.5 to 50 +/- 2.5 mg/dL).
      Thus, the present study clearly shows that the T. grandis Linn. bark extract
      exerts anti-hyperglycemic activity.

PMID- 21170209
TI  - Study of the synergistic anti-inflammatory activity of Solanum xanthocarpum
      Schrad and Wendl and Cassia fistula Linn.
AB  - INTRODUCTION: Nonsteroidal and steroidal drugs are generally used as a part of
      drug therapy in inflammation. However, these drugs have severe side-effects like
      nausea and vomiting. Therefore, there is a need to identify anti-inflammatory
      compounds that will be effective with a better safety profile. Solanum
      xanthocarpum Schrad and Wendl and Cassia fistula Linn has many therapeutic uses
      mentioned in Ayurveda and therefore we aimed to study its anti-inflammatory
      activity both alone and in combination. MATERIALS AND METHODS: The water extract
      of dried fruits of Solanum xanthocarpum Schrad and Wendl and dried pulp of Cassia
      fistula Linn was prepared. The anti-inflammatory activity of these extracts was
      investigated using the carragenan-induced paw edema model in rats individually
      and in two different combinations. ED50 of both the extracts singly and in
      combination were calculated by dose-response curves, and this information was
      then plotted on the isobologram. The interaction index of the extracts was also
      investigated to determine whether both the extracts in combination show
      synergistic or antagonistic or additive effects. RESULTS: It was observed that
      extracts of dried fruits of Solanum xanthocarpum showed more anti-inflammatory
      activity than dried fruits of Cassia fistula Linn. Both the extracts showed
      maximum anti-inflammatory activity at 500 mg/kg dose. Among the different dose
      combinations of both the extracts, the 1:1 combination at the 500 mg/kg dose
      showed maximum percentage inhibition of 75%, which was comparable with the
      positive control, diclofenac sodium, which showed 81% inhibition. CONCLUSION: As
      revealed by the isobolograms, both the combinations fell below the additivity
      line, which indicates synergistic interactions between Solanum xanthocarpum and
      Cassia fistula extracts. Interaction indices of both combinations were observed
      to be <1, which re-demonstrated the synergistic effects of the combination.

PMID- 21170210
TI  - Seminal gold content in healthy fertile men in India.
AB  - OBJECTIVE: Since centuries Ayurveda, mentions the role of gold in the treatment
      of male infertility 'Swarna Bhasma' (Ash of gold) has been used with good results
      by Ayurvedic practitioners in the treatment of infertility. Hence, a study was
      planned to estimate gold in whole semen by atomic absorption spectrophotometry.
      MATERIALS AND METHODS: Whole semen from 11 healthy males of proved fertility from
      Lucknow (India) was analyzed for gold content by Atomic Absorption
      spectrophotometry at wavelength 242.8 nm with Hollow Cathode Gold Lamp. Prior to
      analysis, all the samples were subjected to digestion procedure, achieved by
      treating them with mixture of concentrated Nitric acid and concentrated
      Perchloric acid in 6: 1 ratio. OBSERVATION: On analysis all semen samples were
      found to contain gold ranging from 0.36 to 1.98 MUg/ml with a mean value of 0.88
      MUg/ml and a standard deviation of 0.51 MUg/ml. CONCLUSION: In the present study,
      gold was estimated after complete digestion (oxidation of organic matters; hence,
      whatever amount of gold detected, denotes the levels in seminal plasma as well as
      the sperm itself) in whole semen (seminal plasma and sperm). It seems that the
      hypothesis made for presence of gold in sperm might be true. However, the
      literature available in this connection is very scanty and further studies are
      needed for scientific documentation of gold in male infertility.

PMID- 21170211
TI  - Efficacy and safety of Ayurvedic medicines: Recommending equivalence trial design
      and proposing safety index.
AB  - Ayurvedic drugs have begun to be evaluated in controlled clinical trials. The
      trials, often placebo controlled, are usually designed to demonstrate
      superiority. Though the results have been usually reported as encouraging,
      statistical significance has been elusive. In this melee to show efficacy,
      several positive results related to safety and other purported advantages with
      Ayurvedic drugs, including improved quality of life, easy drug availability and
      less cost, get drowned. Though safety is the prime concern, efficacy ultimately
      matters in trials. Excellent safety profile offset modest efficacy, especially
      for long-term management of chronic difficult to treat disorders. There is a
      trade-off between efficacy and safety but we have no means to put them together
      in a mathematical evaluation to judge the overall performance of a drug. However,
      we need more suitable modern science methods/techniques to unravel the true
      therapeutic role of Ayurvedic drugs. We propose "equivalence trials" using modern
      medicine benchmark as a comparator and a "safety/tolerability index" on this
      perspective. We believe that several Ayurvedic drugs are capable of demonstrating
      equal efficacy but superior safety. Our concept may also be applicable for
      pragmatic trials that are more suitable for Ayurvedic therapy.

PMID- 21170212
TI  - Pilonidal sinus (Nadi vrana): A case study.
AB  - Pilonidal sinus (PNS) occurs in the cleavage between the buttocks (natal cleft)
      and can cause discomfort, embarrassment and absence from work for thousands of
      young people (mostly men) annually. The incidence of the disease is calculated to
      be 26 per 100,000 people. It occurs 2.2 times more often in men than in women.
      Age at presentation is 21 years for men and 19 years for women this case report
      describes a 22-year-old man with pilonidal sinus who was treated with
      ksharasutra.

PMID- 21170213
TI  - Overdose effect of aconite containing Ayurvedic Medicine ('Mahashankha Vati').
AB  - There are chances that the use of larger than recommended dose of Ayurvedic
      medicines containing aconite can produce drug reactions. Vatsanabha (Aconitum
      ferox Wall.) is a very well-known ingredient of Ayurvedic formulations and is
      prescribed as an antipyretic, analgesic, anti-rheumatic, appetizer and digestive.
      The recommended dose of purified Vatsanabha (A. ferox Wall.) root is 15 mg. We
      present a case of hypotension and bradycardia due to aconite poisoning caused by
      overdosing of an Ayurvedic medicine (Mahashankha Vati), which was primarily
      managed by Ayurvedic treatment.

PMID- 21170215
TI  - Career options after Bachelor of Ayurvedic Medicine and Surgery.

PMID- 21170214
TI  - Choosing statistical test.

PMID- 21170216
TI  - Exploring larger evidence base for contemporary Ayurveda.

PMID- 21170217
TI  - Barron's rubber band ligation vs. Kshar Sutra ligation.

PMID- 21170219
TI  - About international federation of societies of endoscopic surgeons.

PMID- 21170218
TI  - More concerns on triphala mouthwash.

PMID- 21170220
TI  - Controversies in laparoscopic repair of incisional hernia.
AB  - BACKGROUND: Incisional hernias can be a significant problem after open abdominal
      surgery. Laparoscopic incisional hernia repair (LIHR) is conceptually appealing:
      a large, abdominal wall re-incision with potential wound-related ill effects is
      avoided and an intra-peritoneal onlay mesh is expected to provide security that
      is equivalent to open, retro-muscular mesh repair. As such, LIHR has gained
      substantial popularity despite sparse, randomised clinical data to compare with
      conventional, open repair. AIM: To enumerate and discuss important, controversial
      issues in patient-selection, technique and early post-operative care for LIHR.
      MATERIALS AND METHODS: Pragmatic summary of comprehensive review of English
      language literature, discussion with experts and personal experience. OUTCOMES:
      SIX IMPORTANT AREAS OF SOME DISPUTE WERE IDENTIFIED: 1. Size of abdominal-wall
      defect that is suitable for LIHR: Generally, defect-diameter > 10 cm is better
      served by open retromuscular repair with tension-free re-approximation of the
      edges of the defect. 2. Extent of adhesiolysis: Complete division of adhesions to
      the anterior abdominal wall may identify sub-clinical "Swiss-cheese" defects but
      incurs some risk of additional complications. 3. Intra-operative recognition of
      enterotomy: Possible options are either laparoscopic suture of bowel injury and
      simultaneous completion of LIHR, or staged LIHR or conversion to open suture
      repair. 4. Choice of mesh: "Composite" meshes are regarded as the current
      standard of care but there is paucity of data regarding potential dangers of
      intra-peritoneal polypropylene mesh. 5. Technique of mesh-fixation: Trans
      parietal sutures are more secure than tacks, with limited data to correlate with
      post-operative pain. 6. Alarm over post-operative pain: Unlike other advanced
      laparoscopic operations, the specificity of pain as a marker of intra-abdominal
      sepsis after LIHR remains unclear. CONCLUSION: Recognition of and attention to
      controversial issues will promote increased success of LIHR.

PMID- 21170221
TI  - Role of pre-operative dexamethasone as prophylaxis for postoperative nausea and
      vomiting in laparoscopic surgery.
AB  - INTRODUCTION: Laparoscopic surgery provides tremendous benefits to patients,
      including faster recovery, shorter hospital stay and prompt return to normal
      activities. Despite the minimally invasive nature of laparoscopy, high incidence
      of postoperative nausea and vomiting remains a major cause for morbidity. The aim
      of the present study was to investigate whether preoperative Dexamethasone can
      reduce PONV in patients undergoing laparoscopic Surgery. MATERIALS AND METHODS:
      The study included 200 patients undergoing laparoscopic cholecystectomy. We
      divided the patients into two groups; one group received preoperative
      Dexamethasone (group 1) and the other group received Ondansetron (group 2). After
      surgery, patients were observed for any episode of nausea or vomiting, or whether
      the patient required any anti-emetic drug in the postoperative period. RESULTS:
      The two groups, (Dexamethasone and Ondansetron) were comparable in outcome, in
      terms of post-operative nausea and vomiting, in patients undergoing laparoscopic
      cholecystectomy. In group I, 24% of patients had nausea, as compared to 30% in
      group II (P=0.2481). Similarly, 12% of patients in group I and 18% of patients in
      group II had vomiting (P=0.3574). CONCLUSION: We conclude that, preoperative
      intravenous low dose Dexamethasone reduces the incidence of PONV and is
      comparable to intravenous Ondansetron.

PMID- 21170223
TI  - Double gallbladder with different disease entities: A case report.
AB  - We report a rare case of gallbladder duplication in a young male patient with
      acute pyocoele in one vesicle and acute cholecystitis with cystadenoma in the
      other; another unusual feature was the absent or obliterated cystic duct in the
      proximal vesicle and non-communication with the second vesicle or the biliary
      system. Ultrasound examination had suggested a septate gallbladder; the diagnosis
      of dual gallbladder was made per-operatively during separation of the distal
      moiety which was presumed to be an adherent duodenum initially. Intraoperative
      cholecystogram confirmed the diagnosis and both gallbladders were removed
      successfully laparoscopically.A high degree of awareness, detailed preoperative
      investigations when anomalies are suspected and intraoperative cholangiography
      are necessary for accurate detailing of the biliary tree to avoid inadvertent
      damage to the biliary ductal system and overlooking of second or third
      gallbladder during surgery.

PMID- 21170222
TI  - Comparison of long-term results of laparoscopic and endoscopic exploration of
      common bile duct.
AB  - BACKGROUND: To compare long term results of laparoscopic and endoscopic
      exploration of common bile duct, to assess post-procedure quality of life.
      MATERIALS AND METHODS: From September 1992 to August 2003, we performed 4058
      cholecystectomies, out of which 479 (11.80%) patients had choledocholithiasis.
      There were 163 males and 316 females. Mean age was 63.65 +/- 5.5 years. These
      patients were put in two groups. In the first group of 240 patients, a majority
      of patients underwent two-stage procedures. ERCP/ES was performed in 210 (87.50%)
      cases. In the second group of 239 patients, a majority of patients underwent
      single-stage procedures. ERCP/ES was done in 32 (13.38%) cases. RESULTS:
      Mortality was zero in both groups. Morbidity was 15.1% in first group and 7.5% in
      second group. Mean hospital stay was 11.7 +/- 3.2 days in first group and 6.2 +/-
      2.1 days in second group. Average operative time was 95.6 +/- 20 minutes in first
      group and 128.4 +/- 32 minutes in second group. Completed questionnaires received
      from 400 (83.50%) patients revealed better long-term results in the second group.
      Clinical features of low-grade cholangitis were seen in 20% of patients who
      underwent ES. Hence the post-procedure quality of life in patients who underwent
      single-stage procedures was definitely much better, because of minimal damage of
      sphincter of Oddi. CONCLUSIONS: Single-stage laparoscopic operations provide
      better results and shorter hospital stay. Damage to sphincter of Oddi should be
      minimal, to avoid long-term low-grade cholangitis. In young patients, the
      operation of choice should be single-stage laparoscopic procedure with absolutely
      no damage to sphincter of Oddi.

PMID- 21170224
TI  - Laparoscopic cholecystectomy in-patient with situs inversus.
AB  - In modern era, laparoscopic surgery is gold standard for gall bladder calculi.
      Situs inversus is a rare condition. To diagnose as well as operate any pathology
      in such patients is difficult. Laparoscopic cholecystectomy in such patient is a
      challenge but not contraindication.

PMID- 21170225
TI  - Umbilical port hernia following laparoscopic cholecystectomy.

PMID- 21170226
TI  - Railroading removal of gall bladder in laparoscopic cholecystectomy.

PMID- 21170227
TI  - Psychiatric disorders and holistic therapies.

PMID- 21170228
TI  - Brainstem auditory-evoked potentials in two meditative mental states.
AB  - CONTEXT: Practicing mental repetition of "OM" has been shown to cause significant
      changes in the middle latency auditory-evoked potentials, which suggests that it
      facilitates the neural activity at the mesencephalic or diencephalic levels.
      AIMS: The aim of the study was to study the brainstem auditory-evoked potentials
      (BAEP) in two meditation states based on consciousness, viz. dharana, and dhyana.
      MATERIALS AND METHODS: Thirty subjects were selected, with ages ranging from 20
      to 55 years (M=29.1; +/-SD=6.5 years) who had a minimum of 6 months experience in
      meditating "OM". Each subject was assessed in four sessions, i.e. two meditation
      and two control sessions. The two control sessions were: (i) ekagrata, i.e.
      single-topic lecture on meditation and (ii) cancalata, i.e. non-targeted
      thinking. The two meditation sessions were: (i) dharana, i.e. focusing on the
      symbol "OM" and (ii) dhyana, i.e. effortless single-thought state "OM". All four
      sessions were recorded on four different days and consisted of three states, i.e.
      pre, during and post. RESULTS: The present results showed that the wave V peak
      latency significantly increased in cancalata, ekagrata and dharana, but no change
      occurred during the dhyana session. CONCLUSIONS: These results suggested that
      information transmission along the auditory pathway is delayed during cancalata,
      ekagrata and dharana, but there is no change during dhyana. It may be said that
      auditory information transmission was delayed at the inferior collicular level as
      the wave V corresponds to the tectum.

PMID- 21170229
TI  - Here and now: Yoga in Israeli schools.
AB  - CONTEXT: In the aftermath of the Second Lebanon War, a project was initiated and
      designed to reduce tension in the children living in the area under bombardment.
      AIMS: To assess the impact of yoga intervention in a group of Israeli school
      children residing in the region affected by the Second Lebanon War. SETTINGS AND
      DESIGN: The study population included 122 school children aged 8-12 years in two
      elementary schools in Safed (n=55 and n=67, respectively) and their teachers
      (n=6). The children attended the third grade (n=28), fourth grade (n=42) and
      sixth grade (n=52). Inclusion in the study was based on the school principal's
      consent to participate in the program. MATERIALS AND METHODS: Assessment was
      conducted using three questionnaires that have been previously validated in
      international studies and translated to Hebrew. STATISTICAL ANALYSIS USED:
      Statistical analysis of the results included Wilcoxon Signed Ranked Tests for pre
      and post-intervention comparisons and the Kruskall-Wallis test for teacher and
      child cross-comparisons. RESULTS: Based on the questionnaires completed by the
      children and their teachers, we found that the teachers reported many
      statistically significant improvements in the children's concentration, mood and
      ability to function under pressure, although the children themselves were unaware
      of any change in their behavior. Enjoyment was reported by all participants, and
      almost all expressed an interest in continuing to practice yoga during school
      hours. We conclude that participation in yoga classes may be both enjoyable and
      beneficial to children living in stressful conditions. CONCLUSIONS: The study
      indicates that yoga may be beneficial as an intervention for children in postwar
      stress situations.

PMID- 21170230
TI  - Does yoga shape body, mind and spiritual health and happiness: Differences
      between yoga practitioners and college students.
AB  - BACKGROUND/AIMS: To assess the body, mind and spirit differences between yoga
      students compared with college students. MATERIALS AND METHODS: Mind, body and
      spirit survey instruments administered to the two groups. RESULTS: Five
      indicators to measure mental wellness were significantly different between yoga
      practitioners and college students. On three of these five measures, college
      students reported more mental wellness than yoga practitioners - in other words,
      the relationship was the inverse of what was expected. College students reported
      maintaining stability in their life more often than yoga practitioners as well as
      more often experiencing satisfying interpersonal relationships. College students
      were also more likely than yoga practitioners to report being tolerant of others,
      whether or not they approved of their behavior or beliefs. Yoga practitioners
      were more likely than college students to report having strong morals and healthy
      values as well as the ability to express their feelings and consider the feelings
      of others. We found differences between yoga practitioners and college students
      on more than half of our spirit items (five of nine). Yoga practitioners were
      more likely than college students to report expressing their spirituality
      appropriately and in healthy ways, recognizing the positive contribution faith
      could make to the quality of life (significant at the 0.07 level), routinely
      undertaking new experiences to enhance spiritual health and having a positive
      outlook on life. Further, we found support for the proposition that yoga
      practitioners were more likely to report experiencing happiness within.
      CONCLUSIONS: Significant differences between yoga and college students were found
      on the body, mind and spirit measurement instrument. Further work needs to
      address the complexities of these relationships.

PMID- 21170231
TI  - Impact of yoga way of life on organizational performance.
AB  - BACKGROUND: Organizational performance can be attributed to a number of factors.
      However, there are certain organizational factors, the presence or absence of
      which can determine the success or failure of the organization. There are
      different ways in which organizations try to improve their performance by working
      on such factors. In the research presented in this article, an attempt is made to
      find out whether adoption of the Yoga Way of Life by managers can have a positive
      impact on such organizational performance indicators. AIMS: To measure effect of
      yoga way of life on five different indicators through an empirical study.
      MATERIALS AND METHODS: The five indicators are job satisfaction, job involvement,
      goal orientation, affective organizational commitment and organizational
      citizenship behavior. STATISTICS ANALYSIS: Pre- and post-data was measured using
      self-reported questionnaire. Independent T-test (Paired) and Pearson's
      correlation test were conducted using SPSS. RESULTS AND CONCLUSION: The results
      of the study show that Yoga has a significant positive impact on four out of five
      of these indicators. Only job involvement does not show significant improvement.
      The construct used for measuring job involvement had a Chronbach alpha of 0.613,
      which is an indicator of moderate reliability, which could be the main reason for
      not getting positive result.

PMID- 21170232
TI  - Immediate effect of two yoga-based relaxation techniques on attention in
      children.
AB  - AIMS: To investigate the effect of two yoga-based relaxation techniques, namely,
      cyclic meditation (CM) and supine rest (SR), using the six letter cancellation
      task (SLCT). MATERIALS AND METHODS: The subjects consisted of 208 school
      students, (132 boys, 76 girls) in the age range of 13 - 16 years. The subjects
      were assessed on SLCT before and immediately after both yoga-based relaxation
      techniques. RESULTS: After both practices, the total and net scores were
      significantly increased, although the magnitude of change was more after CM than
      after SR in the net scores (14.5 versus 11.31%). The net score change in the CM
      session was significantly larger than the change in the SR, whereas, there was no
      significant change in the wrong cancellation score. After either practice, the
      total and net scores were significantly increased, irrespective of gender and
      age. CONCLUSIONS: Both CM and SR led to improvement in performance, as assessed
      by SLCT, but the change caused by CM was larger than SR.

PMID- 21170233
TI  - Effect of Pranayama (voluntary regulated breathing) and Yogasana (yoga postures)
      on lipid profile in normal healthy junior footballers.

PMID- 21170234
TI  - Cerebral oximetry and laparoscopic surgery.

PMID- 21170236
TI  - Laparoscopic adrenalectomy: Gaining experience by graded approach.
AB  - INTRODUCTION: Laparoscopic adrenalectomy (LA) has become a gold standard in
      management of most of the adrenal disorders. Though report on the first
      laparoscopic adrenalectomy dates back to 1992, there is no series of LA reported
      from India. Starting Feb 2001, a graded approach to LA was undertaken in our
      center. Till March 2006, a total of 34 laparoscopic adrenalectomies were
      performed with success. MATERIALS AND METHODS: The endocrinology department
      primarily evaluated all patients. Patients were divided into Group A - unilateral
      LA and Group B - bilateral LA (BLA). The indications in Group A were
      pheochromocytoma (n=7), Conn's syndrome (n=3), Cushing's adenoma (n=2),
      incidentaloma (n=2); and in Group B, Cushing's disease (CD) following failed
      trans-sphenoid pituitary surgery (n = 8); ectopic ACTH- producing Cushing's
      syndrome (n=1) and congenital adrenal hyperplasia (CAH) (n=1). The lateral
      transabdominal route was used. RESULTS: The age group varied from 12-54 years,
      with mean age of 28.21 years. Average duration of surgery in Group A was 166.43
      min (40-270 min) and 190 min (150-310 min) in Group B. Average blood loss was
      136.93 cc (20-400 cc) in Group A and 92.5 cc (40-260 cc) in Group B. There was
      one conversion in each group. Mean duration of surgical stay was 1.8 days (1-3
      days) in Group A and 2.6 days (2-4 days) in Group B. All the patients in both
      groups were cured of their illness. Three patients in Group B developed Nelson's
      syndrome. The mean follow up was of 24.16 months (4-61 months). CONCLUSION: LA
      though technically demanding, is feasible and safe. Graded approach to LA is the
      key to success.

PMID- 21170235
TI  - Twenty years after Erich Muhe: Persisting controversies with the gold standard of
      laparoscopic cholecystectomy.
AB  - This review article is a tribute to the genius of Professor Erich Muhe, a man
      ahead of his times. We trace the development of laparoscopic cholecystectomy and
      detail the tribulations faced by Muhe. On the occasion of the twentieth
      anniversary of the first laparoscopic cholecystectomy, we take another look at
      some of the controversies surrounding this gold standard in the management of
      gallbladder disease.

PMID- 21170237
TI  - Changes in cerebral oximetry during peritoneal insufflation for laparoscopic
      procedures.
AB  - BACKGROUND: Changes in cardiac output may occur during insufflation for
      laparoscopic procedures. However, there are limited data regarding its potential
      effects on cerebral oxygenation. MATERIALS AND METHODS: Cerebral oxygenation
      (ScO(2)), end tidal CO(2), heart rate, blood pressure and oxygen saturation by
      pulse oximetry were recorded every 5 minutes prior to insufflation, during
      insufflation and after desufflation. Minute ventilation was increased to maintain
      normocapnia and the depth of anesthesia was adjusted or fluids/phenylephrine
      administered to maintain the blood pressure within 20% of the baseline. RESULTS:
      The cohort for the study included 70 adults for laparoscopic herniorrhaphy,
      gastric bypass or cholecystectomy. A total of 1004 ScO(2) values were obtained
      during laparoscopy. The ScO(2) decreased from the baseline in 758 of the 1004
      data points. The ScO(2) was 0-9 less than the baseline in 47.8% of the values, 10
      19 less than the baseline in 24.9% of the values and 20-29 less than the baseline
      in 26 values (2.6%). Eighty-two (8.2%) of the values were less than 80% of the
      baseline value, while 25 values (2.5%) were less than 75% of the baseline value.
      Twelve patients had at least one ScO(2) value that was less than 80% of the
      baseline and 6 had at least one ScO(2) value that was less than 75% of the
      baseline. Four patients of the cohort had ScO(2) values less than 80% of the
      baseline for more than 50% of the laparoscopic procedure. CONCLUSIONS: Although
      relatively uncommon, significant changes in cerebral oxygenation do occur in some
      patients during insufflation for laparoscopic surgery.

PMID- 21170239
TI  - Laparoscopic reduction of acute intrathoracic herniation of colon, omentum and
      gastric volvulus.
AB  - Intrathoracic gastric volvulus with herniation of colon and omentum in a
      paraesophageal hernia is a rare occurrence. It may present as an acute surgical
      emergency with life-threatening complications. The diagnosis is usually made by
      imaging studies and endoscopy. Definite treatment is surgery. We present the
      laparoscopic management of this case.

PMID- 21170240
TI  - Vesicovaginal fistula: An unusual complication of laparoscopic assisted
      nephroureterectomy.
AB  - We report a case of vesicovaginal fistula in 71-year-old lady who had previously
      undergone a lapascopic assisted nephroureterectomy for transitional cell
      carcinoma in her right ureter and kidney. The surgery was uncomplicated with no
      post-operative problems and was discharged on day on seven. She later presented
      five weeks following the initial operation with signs and symptoms suggestive of
      a vesicovaginal fistula, which was confirmed on cystogram and flexible cystosopy.
      She proceeded to have an abdominal (O'Connor's) repair of the fistula together
      with cystodiathermy for a few superficial bladder recurrences. The area of the
      fistula (within the bladder) was noted to be tumour free. She had an uneventful
      post-operative recovery and was discharged from hospital on day 11. At six month
      follow-up, there was another superficial recurrence in the bladder that was
      resected, with no sign of fistula.

PMID- 21170238
TI  - Pseudo-aneurysm of the hepatic artery after laparoscopic cholecystectomy: A case
      report.
AB  - Iatrogenic injuries to hepatic artery system may evolve to pseudoaneurysms in the
      late postoperative period. Although rare, pseudoaneurysms after laparoscopic
      cholecystectomy can occur, are a serious clinical entity and very difficult to
      detect.We present a case of iatrogenic pseudoaneurysm after laparoscopic
      cholecystectomy. The onset of symptoms occurred 5 days after an uneventful
      operation. Endovascular coil embolization for a large pseudoaneurysm was
      unsuccessful and open surgery was conducted. Review of the literature reveals
      fifty-four more cholecystectomy-related pseudoaneurysms. The site of injury was
      the right hepatic artery in 61% of the cases and the presenting symptom was
      hemobilia in two-third of the patients. Embolization was performed in 82% of the
      cases and surgery undertaken in the remaining 18%.Knowledge of the condition
      should result in early diagnosis and thus limit the resultant morbidity.
      Embolization is the first line of treatment and surgery is reserved for more
      complex injuries and cases with life-threatening rupture of the aneurysm.

PMID- 21170241
TI  - Transperitoneal laparoscopic approach for retrocaval ureter.
AB  - We had a 14 year old boy, who presented with recurrent attacks of right loin
      pain. Investigations revealed a retrocaval ureter. A transperitoneal three port
      laparoscopic approach was undertaken. The retrocaval portion of ureter was
      excised. A double J stent was placed laparoscopically and ureteroureterostomy was
      done with intracorporeal suturing. The patient was discharged after 72 hours and
      the stent was removed on the 15(th) day. Follow up showed regression of
      hydronephrosis. We recommend this approach compared to open surgery, as it offers
      several advantages compared to conventional open surgery like decreased
      postoperative pain, decreased hospital stay and a cosmetically more acceptable
      surgical scar.

PMID- 21170242
TI  - Are you a "laparoscopic surgeon"?

PMID- 21170243
TI  - Oxidative stress induced by lead and antioxidant potential of certain adaptogens
      in poultry.
AB  - Effect of lead was studied for its action on antioxidant defense in broilers. A
      total of 225 one-day-old male broiler chicks (Vencobb strain) were divided
      randomly into 15 groups consisting of 15 chicks in each group. Group 1 was
      maintained on basal diet, group 2 on polyherbal formulation (PHF; stressroak),
      group 3 on shilajit, group 4 on amla, and group 5 on vitamin E + selenium (Se).
      Group 6 was maintained on lead for 42 days (6 weeks) and group 7 on lead for 28
      days and subsequently on basal diet without lead for the remaining two weeks.
      Groups 8, 9, 10, and 11 were given lead along with PHF, shilajit, amla, and
      vitamin E + Se, respectively throughout the experiment for 6 weeks. Groups 12,
      13, 14, and 15 were given lead containing diet for the first four weeks (28 days)
      and subsequently treated with PHF, shilajit, amla, and vitamin E + Se,
      respectively for the remaining two weeks. Antioxidant status of the birds was
      analyzed by assaying blood samples for glutathione (GSH) peroxidase, GSH
      reductase, and catalase at the end of fourth and sixth weeks, whereas
      Thiobarbituric acid reacting substances (TBARS) and GSH concentrations were
      estimated in liver homogenate at the end of the sixth week. The antioxidant
      defense parameters were significantly altered in toxic control groups indicating
      the possible oxidative damage caused by lead, whereas the parameters were normal
      in control groups 1 to 5 and other groups that were given the drugs in test,
      indicating their good ameliorating activity in oxidative stress.

PMID- 21170244
TI  - Cadmium-induced Oxidative Stress and Evaluation of Embilica Officinalis and
      Stressroak in Broilers.
AB  - Cadmium (Cd) toxicity was studied in broilers, and efficacy of Emblica
      officinalis (500 ppm in feed), vitamin E (300 ppm in feed), and stressroak (1
      g/kg feed) were evaluated for prophylactic and therapeutic management of Cd
      toxicity. One-day-old male broiler chicks were randomly divided into eight groups
      consisting of 10 chicks in each. Groups 1 and 2 were maintained as plain control
      and Cd (100 ppm in feed) toxic control (for six weeks). Groups 3, 4, and 5 were
      maintained on a combination of Cd (100 ppm in feed) and Emblica officinalis,
      vitamin E, and stressroak for six weeks. Groups 6, 7, and 8 were maintained with
      Cd for the first four weeks and on Emblica officinalis, vitamin E, and stressroak
      during the subsequent two weeks without Cd. Body weights, feed consumed, Feed
      conversion ratio (FCR), and glulathione (GSH) were significantly (P<0.05)
      decreased, whereas the activities of antioxidant enzymes (catalase and Superoxide
      dismutase (SOD)) and concentration of Thiobarbituric acid reacting substances
      (TBARS) were significantly (P<0.05) increased in toxic control group. After
      treatment with Emblica officinalis, vitamin E, and stressroak in groups 6, 7, and
      8 during last two weeks and discontinuation of Cd, the parameters revealed
      improvement. From this study, it is concluded that Cd induces toxicity by
      oxidative stress, and supplementing Emblica officinalis, vitamin E, and
      stressroak in feed is useful in preventing and treating the toxicity.

PMID- 21170245
TI  - Zinc toxicity to aminergic neurotransmitters in rat brain.
AB  - The present study was aimed to evaluate zinc toxicity to aminergic system in
      different areas of the brain of male albino rat, Rattus norvegicus. Zinc
      toxicity, evaluated as per Probit method was found to be 500 mg/kg body weight.
      For acute-dose studies, rats were given a single lethal dose of zinc chloride for
      one day only and for chronic-dose studies, the rats were administered with sub
      lethal doses (1/10(th) of lethal dose) of zinc chloride every day for 90 days
      continuously. Various constituents of the aminergic system viz. dopamine,
      norepinephrine, and epinephrine and the catabolizing enzyme, monoamine oxidase
      (MAO) were determined in different regions of rat brain such as olfactory lobe,
      hippocampus, cerebellum, and pons-medulla on selected time intervals/days under
      acute and chronic treatment with zinc. The results revealed that while the levels
      of all aminergic neurotransmitters were elevated differentially in the above
      mentioned areas of brain, MAO activity registered nonsignificant inhibition in
      all brain regions under zinc toxicity. All these changes in the aminergic system
      were subsequently manifested in the behavior of rat exhibiting the symptoms of
      mild tremors, reduced locomotor activity and emotions, restlessness followed by
      lacrymation, salivation, etc. From these observations, it was obvious that zinc
      treatment caused severe perturbations in the functions of the nervous system.
      Restoration of the aminergic system along with behavior to the near normal levels
      under chronic treatment indicates the onset of detoxification mechanisms or
      development of tolerance to zinc toxicity in the animal which was not probably so
      efficient under acute treatment.

PMID- 21170246
TI  - Reversal of Cadmium-induced Oxidative Stress in Chicken by Herbal Adaptogens
      Withania Somnifera and Ocimum Sanctum.
AB  - The present study was carried out to evaluate the herbal adaptogens Withania
      somnifera and Ocimum sanctum on cadmium-induced oxidative toxicity in broiler
      chicken. Cadmium administration at the rate of 100 ppm orally along with feed up
      to 28 days produced peroxidative damage, as indicated by increase in TBARS,
      reduction in glutathione (GSH) concentration in liver and kidney, and increase in
      catalase (CAT) and superoxide dismutase (SOD) of erythrocytes. Herbal adaptogens
      Withania somnifera roots and Ocimum sanctum leaf powder administration at the
      rate of 0.1% through feed reversed the antioxidant enzyme of RBC, i.e., CAT and
      SOD, nonenzymatic antioxidants GSH and lipid peroxidation marker TBARS of liver
      and kidney. Liver and kidney tissue repair and normal function was assessed by
      alanine aminotransaminase for liver and creatinine and blood urea nitrogen for
      kidney. In conclusion, oral administration of Withania somnifera root and Ocimum
      sanctum leaf powder prevented cadmium-induced peroxidation of tissues.

PMID- 21170247
TI  - Acetaminophen-induced Hepato- and Nephrotoxicity and Amelioration by Silymarin
      and Terminalia chebula in Rats.
AB  - Experimental study was conducted to evaluate the hepato- and renoprotective
      effect of silymarin and Terminalia chebula against experimentally-induced
      acetaminophen (APAP) toxicity in rats. Oral administration of APAP @ 500 mg/kg
      for 1 to 3 days to all the four groups (six rats in each) resulted in significant
      elevation of serum triglycerides, total cholesterol, blood urea nitrogen, serum
      creatinine, and aspartate transaminase activity. Post-treatment with silymarin @
      25 mg/kg and T. chebula 125 mg/kg in groups 2 and 3 and their combination to
      group 4 from day 4 to 14 has significantly reversed the alterations of above said
      markers and offered better protection. The results of the study enunciated that
      silymarin and T. chebula exhibit good hepato- and nephro-protection against APAP
      toxicity.

PMID- 21170248
TI  - Biochemical Changes after Short-term Oral Exposure of Jatropha curcas Seeds in
      Wistar Rats.
AB  - Jatropha curcas (Euphorbiaceae) is a multipurpose shrub with varied medicinal
      uses and is of significant economic importance. In addition to being the source
      of biodiesel, its seeds are also considered highly nutritious and could be
      exploited as a rich and economical protein supplement in animal feeds. However,
      the inherent phytotoxins present in the seed is the hindrance. The toxicity
      nature of the seeds of the local variety of J. curcas is not known. Therefore,
      investigations were undertaken to evaluate the short-term oral toxicity of the
      seeds of locally grown J. curcas. Short-term toxicity was conducted in rats by
      daily feeding the basal diet (Group I), and the diet in which the crude protein
      requirement was supplemented at 25% (Group II) and 50% (Group III) levels through
      Jatropha seed powder. The adverse effects of Jatropha seed protein
      supplementation (JSPS) were evaluated by observing alterations in biochemical
      profiles. The biochemical profile of rats fed on diet with JSPS at both the
      levels revealed significant reduction in plasma glucose and total protein and
      increase in plasma creatinine, transaminases (Plasma glutamic pyruvic
      transaminase and Plasma glutamic oxaloacetic transaminase), and alkaline
      phosphatase.

PMID- 21170249
TI  - Studies on the changes in lipid peroxidation and antioxidants in fishes exposed
      to hydrogen sulfide.
AB  - In the present aquarium study, Oreochromis mossambicus Peters were exposed to two
      different concentrations of hydrogen sulfide (H(2)S) (4.9 and 6.6 mg/l), and the
      changes in lipid peroxidation (LP) products and antioxidants in test fishes were
      determined in time intervals of 12, 24, 48, 72, and 96 hours. The results showed
      that with respect to the H(2)S concentration and duration of exposure,
      alterations were observed in the concentration of LP products and antioxidants in
      the various organs of the test fishes. Malondialdehyde (MDA) content increased in
      the liver, gill, kidney, and brain on exposure to H(2)S up to 48 hours, and then
      the MDA content showed steady value up to 98 hours experimental period. Brain and
      kidney of fishes showed the maximum increase in concentration of reduced
      glutathione (GSH) on H(2)S treatment. The gradual decrease in concentration of
      GSH in the tissues of H(2) S-exposed fishes after 48 to 96 hours compared with
      the control shows the loss of adaptive mechanisms and the oxidation of GSH to
      glutathione disulphide (GSSG). Slight increase in the activity of GSH-S
      transferase and decrease in activity of GSH peroxidase demonstrated the
      incapability of the vital organs in neutralizing the peroxides generated in the
      oxidative stress condition.

PMID- 21170250
TI  - Neuropathological studies of chickens following exposure to chlorpyrifos.
AB  - The objective of this study was to determine the putative neuropathological
      effects in young chickens after administration of a single dose of 55 mg/kg bw
      chlorpyrifos. The gross lesions of the nervous system comprised of congestions in
      the brain. Microscopic examination of brain showed mild congestion of cerebral
      blood vessels and mild perivascular cuffing of lymphomononuclear cells in the
      cerebral cortex and necrosis of the neurons. The interesting findings were the
      presence of cytoplasmic vacuolations of cerebral neurons and swelling of the
      endothelial cell of the cerebral capillaries. Cerebellum showed congestion and
      hemorrhages in the granular layer and necrosis of Purkinje cell. Sciatic nerve
      exhibited mild edema, swelling and degeneration of axons, and swelling of Schwann
      cells. There was a significant inhibition of plasma cholinesterase enzyme
      activity in chickens administered with chlorpyrifos compared to chickens of
      control group. The study revealed that administration of chlorpyrifos produces
      neuropathological lesions in chickens shortly after exposure.

PMID- 21170251
TI  - Haematolohical profile of subacute oral toxicity of molybdenum and ameliorative
      efficacy of copper salt in goats.
AB  - Molybdenum toxicity produces a state of secondary hypocuprosis, resulting into
      alterations in normal hematological profile. In the present study, ammonium
      molybdate alone and with copper sulfate (II) pentahydrate (ameliorative agent)
      was administered orally for 30 consecutive days in healthy goats of group 1 and
      2, respectively, to access the effect on the hematological profile on different
      predetermined days of dosing. Administration of ammonium molybdate alone produced
      significant decline in the mean values of hemoglobin (Hb), packed cell volume
      (PCV), total leukocyte count (TLC), total erythrocyte count (TEC), and mean
      corpuscular hemoglobin concentration (MCHC), with a significant increase in
      neutrophil level and mean corpuscular volume (MCV). However, values of
      erythrocyte sedimentation rate, mean corpuscular hemoglobin, and differential
      leukocyte count were not significantly altered. On comparing observations of
      ameliorative group with the group 1 goats, it is concluded that the ameliorative
      copper salt has beneficial effects in alleviating the alterations in the values
      of Hb, PCV, TLC, TEC, MCV, MCHC, and neutrophils.

PMID- 21170252
TI  - Study of nephrotoxic potential of acetaminophen in birds.
AB  - The present study was designed to evaluate the effect of acetaminophen on kidneys
      of birds by comparison with diclofenac that is used as positive control. The
      birds of Group I served as negative control and received normal saline, whereas
      Group II birds received diclofenac injection (2.5 mg/kg IM) and Group III birds
      received acetaminophen injection (10 mg/kg IM) for a period of seven days daily.
      The birds treated with diclofenac showed severe clinical signs of toxicity
      accompanied with high mortality and significant increase (P<0.001) in serum
      creatinine and uric acid concentration. The creatinine and uric acid
      concentrations were consistent with gross and histopathological findings. The
      negative control and acetaminophen-treated groups showed no adverse clinical
      signs, serum creatinine and uric acid concentrations were normal, and no gross or
      histopathological changes in kidneys were observed. Thus, it was concluded that
      acetaminophen can be used for treatment in birds without any adverse effect on
      kidneys.

PMID- 21170253
TI  - Interaction study on garlic and atorvastatin with reference to nephrotoxicity in
      dyslipidaemic rats.
AB  - A total of 56 male Sprague dawley rats of uniform weight and age were randomly
      divided into seven groups consisting of eight rats in each group. Groups 1, 2,
      and 3 served as plain control, dyslipidaemic control (DL), and atorvastatin
      control, respectively. Groups 4, 5, 6, and 7 received 1, 0.5, 0.25, and 0.75%
      fresh garlic w/w in feed, respectively in addition to the high-fat and high
      cholesterol diet and administered with atorvastatin orally for 12 weeks at the
      rate of 10, 5, 7.5, and 2.5 mg/kg b.wt., respectively. Plasma creatinine was
      estimated at 4-week intervals, whereas histopathology, electron microscopy, and
      estimation of TBARS concentration in kidney were conducted at the end of
      experiment. The TBARS concentration in DL was significantly (P<0.05) increased
      when compared with groups 1, 3, 6, and 7. On histopathological examination,
      kidney sections of group 3 had mild degenerative changes in the tubules with
      fatty change in few tubules, while groups 4 and 5 exhibited mild-to-moderate
      degenerative and fatty changes in tubules with inter tubular hemorrhages. The
      electron microscopy of group 2 showed hypertrophy of Bowman's capsule, while that
      of group 4 showed secretary deposits in the cytoplasm. The interaction studies on
      kidney indicated that high dose of atorvastatin + garlic has negative safety
      profile when compared with groups having low dose of statin and high dose of
      garlic.

PMID- 21170254
TI  - Toxic impacts of cypermethrin on behavior and histology of certain tissues of
      albino rats.
AB  - In the present investigation, the behavioral, morphological, and
      histopathological effects of cypermethrin, a widely used synthetic pyrethroid
      insecticide, was ascertained in male and female albino rats (Rattus norvegicus).
      Cypermethrin administered at repeated oral doses of 5 and 20 mg/kg/day for 30
      days produced varying degree of mild to moderate toxic symptoms and behavioral
      changes in both male and female rats. The lower dose produced very mild toxicosis
      characterized by intermittent diarrhea, decreased feed intake, and thick eye
      discharge, whereas higher dose displayed mild to moderate toxicosis with
      diarrhea, decreased feed intake, loss of body weight, dyspnoea, ataxia, eye
      discharge, and salivation. Two female and one male albino rats died between 23 to
      28 days after displaying signs of incoordination and tremors. Repeated oral doses
      of cypermethrin for 30 days enhanced the relative weight of liver and heart, but
      significantly decreased that of brain, kidneys, and testes. Microscopically,
      cypermethrin produced neuronal degeneration and increase in glial cells in brain,
      and disorganization of hepatic laminae, increase in sinusoid, and necrosis of
      hepatocytes in liver. Section of kidney displayed hemorrhage and sloughing off
      renal epithelial cell in the convoluted tubules, shrinkage of glomeruli, and
      necrosis of renal tubules. Repeated administration of cypermethrin also produced
      hemorrhages within myocardium, disruption of branching structure, and loss of
      striation of cardiac tissue; thickening of alveolar septa in lungs, partial to
      extensive loss of various stages of spermatogenesis in testes, and loss of
      follicular cells and oocytes in ovaries. The study suggested that repeated oral
      exposure of cypermethrin has considerable harmful effects on body organs in R.
      norvegicus.

PMID- 21170255
TI  - Sero-biochemical Studies in Sheep Fed with Bt Cotton Plants.
AB  - An experimental study was conducted to evaluate the toxicological effects, if
      any, due to feeding of Bt (Bacillus thuringiensis) cotton plants to sheep. A
      total of 32 sheep of one year of age belonging to Deccani breed were randomly
      divided into four groups, consisting of eight sheep in each group. Group 1 was
      maintained on basal diet (concentrate feed at the rate of 300 g + green fodder at
      the rate of 3 kg/sheep/day), group 2 on non-Bt cotton plant at the rate of 1.5 kg
      + green fodder at the rate of 1.5 kg + concentrate feed at the rate of 300
      g/sheep/day, group 3 on Bt cotton plants (50%) at the rate of 1.5 kg + green
      fodder at the rate of 1.5 + concentrate feed at the rate of 300 g/sheep/day, and
      group 4 on Bt cotton plants ad libitum + concentrate feed at the rate of 300
      g/sheep/day. All the groups of sheep were maintained for three months and various
      hemato-biochemical parameters were studied at monthly intervals. The activity of
      aspartate transaminase, gamma glutamyltransferase, and creatine kinase in sera
      samples, and the concentration of blood urea nitrogen and creatinine did not
      differ significantly among different groups at different time intervals. The
      histological examination of liver and kidney did not reveal any significant
      changes in Bt and non-Bt cotton-fed groups. In conclusion, the results of the
      present investigation enunciated that feeding of genetically modified (Bt) cotton
      plants to sheep was without detrimental effects in the biological system of
      sheep.

PMID- 21170256
TI  - Analysis of Metals Concentration in the Soils of SIPCOT Industrial Complex,
      Cuddalore, Tamil Nadu.
AB  - Phytoremediation is a promising area of new research, both for its low cost and
      great benefit to society in the clean retrieval of contaminated sites.
      Phytoremediation is the use of living green plants for in situ risk reduction
      and/or removal of contaminants from contaminated soil, water, sediments, and air.
      Specially selected or engineered plants are used in the process. The soil samples
      were taken from Cuddalore Old Town (OT) and the samples from SIPCOT industrial
      complex, which was the study area and analyzed for various metals concentrations.
      Fifteen metals have been analyzed by adopting standard procedure. The detection
      limits of metal concentration are drawn as control. The various (15) metal
      concentrations in the soil samples were found higher in soil taken from SIPCOT
      industrial complex, compared with samples taken from Cuddalore OT. In all the
      observations, it was found that most of the metals like calcium, cadmium,
      chromium, cobalt, nickel, and zinc showed maximum concentrations, whereas
      arsenic, antimony, lead, magnesium, sodium have shown minimum concentrations,
      both when compared with control. From the present study, it was found that the
      soil collected from SIPCOT complex area were more polluted due to the presence of
      various industrial effluents, municipal wastes, and sewages when compared with
      the soil collected from Cuddalore OT.

PMID- 21170257
TI  - Cholinergic system under aluminium toxicity in rat brain.
AB  - The present investigation envisages the toxic effects of aluminium on the
      cholinergic system of male albino rat brain. Aluminium toxicity (LD(50)/24 h)
      evaluated as per Probit method was found to be 700 mg/kg body weight. One-fifth
      of lethal dose was taken as the sublethal dose. For acute dose studies, rats were
      given a single lethal dose of aluminium acetate orally for one day only and for
      chronic dose studies, the rats were administered with sublethal dose of aluminium
      acetate once in a day for 25 days continuously. The two constituents of the
      cholinergic system viz. acetylcholine and acetylcholinesterase were determined in
      selected regions of rat brain such as cerebral cortex, hippocampus, hypothalamus,
      cerebellum, and pons-medulla at selected time intervals/days under acute and
      chronic treatment with aluminium. The results revealed that while
      acetylcholinesterase activity was inhibited, acetylcholine level was elevated
      differentially in all the above mentioned areas of brain under aluminium
      toxicity, exhibiting area-specific response. All these changes in the cholinergic
      system were subsequently manifested in the behavior of rat exhibiting the
      symptoms such as adipsia, aphagia, hypokinesia, fatigue, seizures, etc.
      Restoration of the cholinergic system and overt behavior of rat to the near
      normal levels under chronic treatment indicated the onset of either
      detoxification mechanisms or development of tolerance to aluminium toxicity in
      the animal which was not probably so efficient under acute treatment.

PMID- 21170258
TI  - Biochemistry on the human scale.

PMID- 21170259
TI  - Autocrine and paracrine actions of vitamin d.
AB  - Vitamin D deficiency continues to attract considerable attention because of
      claims that an adequate status can reduce the risk of a wide range of diseases.
      The facts are that this hormone modulates the expression of a very large number
      of genes, possibly some 5 to 10% of the genome; that it has been subject to very
      strong evolutionary pressures; and that its biological activities are exerted
      across a wide range of tissues, and these all contribute to the plausibility that
      such claims may eventually be found to be valid. While the endocrine action of
      the active metabolite, 1,25-dihydroxyvitamin D, has been well-characterised to
      contribute to maintaining plasma calcium and phosphate homeostasis through
      regulation of intestinal absorption, recent research has focused on its autocrine
      and/or paracrine activities. Such activities of vitamin D have been best
      characterised in skin tissues and the immune system where it regulates cell
      differentiation and maturation as well as the innate immune system. Recent data
      are now available to implicate autocrine/paracrine activities in each of the
      major bone cell types where it also regulates cell proliferation and
      differentiation. In rodent models, adequate levels of serum 25-hydroxyvitamin D
      have been found to be critical to optimise bone health and to protect against
      osteoporosis. These findings are consistent with clinical data that such activity
      is present in humans. The introduction of an autocrine/paracrine paradigm for
      vitamin D has significant implications for critical levels of serum 25
      hydroxyvitamin D for optimal health.

PMID- 21170261
TI  - Induction of DeltaNp63 by the newly identified keratinocyte-specific transforming
      growth factor beta Signaling Pathway with Smad2 and IkappaB Kinase alpha in
      squamous cell carcinoma.
AB  - The expression of p63 (TP63/p51) occurs in the basal cells of stratified
      epithelia and is strongly enhanced at the early stages of squamous cell
      carcinomas (SCCs) of the head and neck, skin, cervix, and others. We analyzed a
      promoter/enhancer region (2kDeltaN) that drives the predominant expression of
      DeltaNp63 for sensitivity to Smad signaling pathways. Reporter assays in HepG2
      cells showed a moderate activation of 2kDeltaN by Smad2 and IkappaB kinase alpha
      (IKKalpha), partners of the newly identified keratinocyte-specific transforming
      growth factor beta (TGF-beta) signaling, but not by other Smad molecules. In A431
      cells, 2kDeltaN was activated by Smad2 and IKKalpha, for which a Smad binding
      element (SMD2) at -204 was essential. Binding of Smad2 to the chromosomal SMD2
      site was detectable. The association of Smad2 with IKKalpha was evident in the
      nucleus of A431, accounting for the enhancement of DeltaNp63 expression by TGF
      beta. Moreover, both DeltaNp63 and IKKalpha were necessary to maintain the
      noninvasive phenotype of this cell line. FaDu, an invasive, Smad4-deficient SCC,
      also allowed 2kDeltaN transactivation by transfected Smad2 in the presence of
      endogenous IKKalpha. Reflecting the lack of chromosomal SMD2-Smad2 association
      and the absence of nuclear IKKalpha, however, endogenous DeltaNp63 was not
      controlled by TGF-beta or IKKalpha in FaDu. SCC tissue arrays showed nuclear
      accumulation of IKKalpha and p63 intensification in well-differentiated
      noninvasive lesions. This study indicates that p63 is a target gene of the
      proposed keratinocyte-specific TGF-beta signal pathway for suppression of the
      malignant conversion of SCC.

PMID- 21170262
TI  - RalBP1 is necessary for metastasis of human cancer cell lines.
AB  - RalA expression in human prostate cancer is associated with cell migration and is
      necessary for bone metastasis. However, the downstream effectors of RalA that
      mediate these functions remain unclear. Here we examined cell migration after
      small interfering RNA-mediated depletion of Ral effectors Ral binding protein 1
      (RalBP1/RLIP), exocyst complex component 2 (Sec5), and phospholipase D1 (PLD1)
      and found that RalBP1 and RalA depletion inhibited cell migration to a similar
      extent. Stable lentivirus short hairpin interfering RNA-mediated depletion of
      RalA and RalBP1 in PC3 human prostate cancer cells inhibited bone metastasis
      after intracardiac inoculation. Depletion of RalBP1 diminished orthotopic tumor
      growth of PC3 cells and inhibited spontaneous metastasis from this site.
      Interestingly, the expression of wild-type or RalA mutants deficient in RalBP1
      binding was effective at rescuing the reduced metastatic capacity of RalA
      depleted PC3 cells, suggesting that RalA depletion does not reduce this solely by
      diminished interaction with RalBP1. To determine whether the role of RalBP1 in
      metastasis is relevant beyond prostate cancer, we studied the requirement of
      RalBP1 expression in an experimental metastasis model of human bladder cancer, a
      tumor type with high RalBP1 expression. Depletion of RalBP1 in UMUC3 cells
      resulted in decreased lung colonization while having a minimal effect on
      subcutaneous tumor growth. Our studies are the first to suggest that the
      expression of RalBP1 is necessary for human cancer cell metastasis. Furthermore,
      we show that the requirement for RalA expression for manifestation of this
      phenotype is not entirely dependent on a RalA-RalBP1 interaction.

PMID- 21170263
TI  - Dexamethasone-induced oxidative stress enhances myeloma cell radiosensitization
      while sparing normal bone marrow hematopoiesis.
AB  - Dexamethasone (Dex) and radiation therapy are established modalities in multiple
      myeloma. In this study, we propose a novel combination of Dex plus radiation that
      shows superior clonogenic cell killing and apoptosis of myeloma cells and
      selectively eliminates myeloma cells when cocultured with bone marrow stromal
      cells (BMSCs). Dex was found to inhibit the release of interleukin-6 from
      irradiated BMSCs, which is an established myeloma cell proproliferative cytokine.
      In 5TGM1 model, the combination of Dex with skeletal targeted radiotherapy (153
      Sm-EDTMP) prolonged median survival time and inhibited radiation-induced
      myelosuppression. A two-cycle treatment of Dex plus 153-Sm-EDTMP was well
      tolerated and further improved median survival time. Mechanistically, Dex
      increased superoxide and hydrogen peroxide production and augmented radiation
      induced oxidative stress and cell death of myeloma cells. In contrast, Dex
      inhibited radiation-induced increase in pro-oxidant levels and enhanced the
      clonogenic survival in normal hematopoietic stem and progenitor cells. Treatment
      with either N-acetylcysteine or the combination of polyethylene glycol (PEG)
      conjugated copper, zinc-superoxide dismutase, and PEG-catalase significantly
      protected myeloma cells from Dex-induced clonogenic death. Overall, these results
      demonstrate that Dex in combination with radiotherapy enhances the killing of
      myeloma cells while protecting normal bone marrow hematopoiesis through a
      mechanism that involves selective increases in oxidative stress.

PMID- 21170264
TI  - Identification of a preneoplastic gene expression profile in tubal epithelium of
      BRCA1 mutation carriers.
AB  - Microinvasive carcinomas and high-grade intraepithelial neoplasms are commonly
      discovered within the fallopian tube of BRCA1 mutation carriers at the time of
      risk-reducing salpingo-oophorectomy, suggesting that many BRCA1-mutated ovarian
      carcinomas originate in tubal epithelium. We hypothesized that changes in gene
      expression profiles within the histologically normal fallopian tube epithelium of
      BRCA1 mutation carriers would overlap with the expression profiles in BRCA1
      mutated ovarian carcinomas and represent a BRCA1 preneoplastic signature. Laser
      capture microdissection of frozen sections was used to isolate neoplastic cells
      or histologically normal fallopian tube epithelium, and expression profiles were
      generated on Affymetrix U133 Plus 2.0 gene expression arrays. Normal-risk
      controls were 11 women wild type for BRCA1 and BRCA2 (WT-FT). WT-FT were compared
      with histologically normal fallopian tube epithelium from seven women with
      deleterious BRCA1 mutations who had foci of at least intraepithelial neoplasm
      within their fallopian tube (B1-FTocc). WT-FT samples were also compared with 12
      BRCA1 ovarian carcinomas (B1-CA). The comparison of WT-FT versus B1-FTocc
      resulted in 152 differentially expressed probe sets, and the comparison of WT-FT
      versus B1-CA resulted in 4079 differentially expressed probe sets. The BRCA1
      preneoplastic signature was composed of the overlap between these two lists,
      which included 41 concordant probe sets. Genes in the BRCA1 preneoplastic
      signature included several known tumor suppressor genes such as CDKN1C and EFEMP1
      and several thought to be important in invasion and metastasis such as E2F3. The
      expression of a subset of genes was validated with quantitative reverse
      transcription-polymerase chain reaction and immunohistochemistry.

PMID- 21170265
TI  - NHERF1/EBP50 is a new marker in colorectal cancer.
AB  - Human colorectal cancer (CRC) arises from activating mutations in the Wnt/beta
      catenin pathway that converge with additional molecular changes to shape tumor
      development and patient prognosis. We report here that Na(+)/H(+) exchanger 3
      regulating factor 1 (NHERF1)/EBP50, an adaptor molecule that interacts with beta
      catenin, undergoes successive alterations during the colorectal adenoma-to
      carcinoma transition, ranging from loss of normal apical membrane distribution to
      ectopic cytoplasmic overexpression. NHERF1 depletion in human intestinal
      epithelial polarized cells induced epithelial-mesenchymal transition, beta
      catenin nuclear translocation with elevation of Wnt/beta-catenin transcriptional
      targets, and increased cell migration and invasion. Ectopic cytoplasmic NHERF1
      expression additionally intensified the transformed phenotype by increasing cell
      proliferation. The epithelial morphology and reduced cell motility could only be
      restored by re-expression of NHERF1 specifically at the apical plasma membrane.
      We conclude that alterations in the apical membrane localization of NHERF1
      contribute to CRC through the disruption of epithelial morphology. This study
      identifies NHERF1 as a new player in CRC progression and supports the notion that
      the expression or subcellular distribution of NHERF1 may be used as diagnostic
      marker for CRC.

PMID- 21170260
TI  - Dinosaurs and ancient civilizations: reflections on the treatment of cancer.
AB  - Research efforts in the area of palaeopathology have been seen as an avenue to
      improve our understanding of the pathogenesis of cancer. Answers to questions of
      whether dinosaurs had cancer, or if cancer plagued ancient civilizations, have
      captured the imagination as well as the popular media. Evidence for dinosaurian
      cancer may indicate that cancer may have been with us from the dawn of time.
      Ancient recorded history suggests that past civilizations attempted to fight
      cancer with a variety of interventions. When contemplating the issue why a
      generalized cure for cancer has not been found, it might prove useful to reflect
      on the relatively limited time that this issue has been an agenda item of
      governmental attention as well as continued introduction of an every evolving
      myriad of manmade carcinogens relative to the total time cancer has been present
      on planet Earth. This article reflects on the history of cancer and the progress
      made following the initiation of the "era of cancer chemotherapy."

PMID- 21170266
TI  - Anticancer effects of the nitric oxide-modified saquinavir derivative saquinavir
      NO against multidrug-resistant cancer cells.
AB  - The human immunodeficiency virus (HIV) protease inhibitor saquinavir shows
      anticancer activity. Although its nitric oxide-modified derivative saquinavir-NO
      (saq-NO) was less toxic to normal cells, it exerted stronger inhibition of B16
      melanoma growth in syngeneic C57BL/6 mice than saquinavir did. Saq-NO has been
      shown to block proliferation, upregulate p53 expression, and promote
      differentiation of C6 glioma and B16 cells. The anticancer activity of substances
      is frequently hampered by cancer cell chemoresistance mechanisms. Therefore, we
      here investigated the roles of p53 and the ATP-binding cassette (ABC)
      transporters P-glycoprotein (P-gp), multidrug resistance-associated protein 1
      (MRP1), and breast cancer resistance protein 1 (BCRP1) in cancer cell sensitivity
      to saq-NO to get more information about the potential of saq-NO as anticancer
      drug. Saq-NO exerted anticancer effects in lower concentrations than saquinavir
      in a panel of human cancer cell lines. Neither p53 mutation or depletion nor
      expression of P-gp, MRP1, or BCRP1 affected anticancer activity of saq-NO or
      saquinavir. Moreover, saq-NO sensitized P-gp-, MRP1-, or BCRP1-expressing cancer
      cells to chemotherapy. Saq-NO induced enhanced sensitization of P-gp- or MRP1
      expressing cancer cells to chemotherapy compared with saquinavir, whereas both
      substances similarly sensitized BCRP1-expressing cells. Washout kinetics and ABC
      transporter ATPase activities demonstrated that saq-NO is a substrate of P-gp as
      well as of MRP1. These data support the further investigation of saq-NO as an
      anticancer drug, especially in multidrug-resistant tumors.

PMID- 21170267
TI  - ERG cooperates with androgen receptor in regulating trefoil factor 3 in prostate
      cancer disease progression.
AB  - To elucidate the role of ETS gene fusions in castration-resistant prostate cancer
      (CRPC), we characterized the transcriptome of 54 CRPC tumor samples from men with
      locally advanced or metastatic disease. Trefoil factor 3 (TFF3) emerged as the
      most highly differentially regulated gene with respect to ERG rearrangement
      status and resistance to hormone ablation therapy. Conventional chromatin
      immunoprecipitation (ChIP)-polymerase chain reaction and ChIP followed by DNA
      sequencing (ChIP-seq) revealed direct binding of ERG to ETS binding sites in the
      TFF3 promoter in ERG-rearranged prostate cancer cell lines. These results were
      confirmed in ERG-rearranged hormone-naive prostate cancer (HNPC) and CRPC tissue
      samples. Functional studies demonstrated that ERG has an inhibitory effect on
      TFF3 expression in hormone-naive cancer but not in the castration-resistant
      state. In addition, we provide evidence suggesting an effect of androgen receptor
      signaling on ERG-regulated TFF3 expression. Furthermore, TFF3 overexpression
      enhances ERG-mediated cell invasion in CRPC prostate cancer cells. Taken
      together, our findings reveal a novel mechanism for enhanced tumor cell
      aggressiveness resulting from ERG rearrangement in the castration-resistant
      setting through TFF3 gene expression.

PMID- 21170268
TI  - Trefoil factor 3 is oncogenic and mediates anti-estrogen resistance in human
      mammary carcinoma.
AB  - We report herein that trefoil factor 3 (TFF3) is oncogenic and mediates anti
      estrogen resistance in human mammary carcinoma. Forced expression of TFF3 in
      mammary carcinoma cells increased cell proliferation and survival, enhanced
      anchorage-independent growth, and promoted migration and invasion. Moreover,
      forced expression of TFF3 increased tumor size in xenograft models. Conversely,
      depletion of endogenous TFF3 with small interfering RNA (siRNA) decreased the
      oncogenicity and invasiveness of mammary carcinoma cells. Neutralization of
      secreted TFF3 by antibody promoted apoptosis, decreased cell growth in vitro, and
      arrested mammary carcinoma xenograft growth. TFF3 expression was significantly
      correlated to decreased survival of estrogen receptor (ER)-positive breast cancer
      patients treated with tamoxifen. Forced expression of TFF3 in mammary carcinoma
      cells increased ER transcriptional activity, promoted estrogen-independent
      growth, and produced resistance to tamoxifen and fulvestrant in vitro and to
      tamoxifen in xenograft models. siRNA-mediated depletion or antibody inhibition of
      TFF3 significantly enhanced the efficacy of antiestrogens. Increased TFF3
      expression was observed in tamoxifen-resistant (TAMR) cells and antibody
      inhibition of TFF3 in TAMR cells improved tamoxifen sensitivity. Functional
      antagonism of TFF3 therefore warrants consideration as a novel therapeutic
      strategy for mammary carcinoma.

PMID- 21170271
TI  - Cellular reactive oxygen species inhibit MPYS induction of IFNbeta.
AB  - Many inflammatory diseases, as well as infections, are accompanied by elevation
      in cellular levels of Reactive Oxygen Species (ROS). Here we report that MPYS,
      a.k.a. STING, which was recently shown to mediate activation of IFNbeta
      expression during infection, is a ROS sensor. ROS induce intermolecular disulfide
      bonds formation in MPYS homodimer and inhibit MPYS IFNbeta stimulatory activity.
      Cys-64, -148, -292, -309 and the potential C88xxC91 redox motif in MPYS are
      indispensable for IFNbeta stimulation and IRF3 activation. Thus, our results
      identify a novel mechanism for ROS regulation of IFNbeta stimulation.

PMID- 21170269
TI  - Noninvasive detection of inflammation-associated colon cancer in a mouse model.
AB  - Helicobacter bilis-infected Smad3(-/-) mice represent an attractive model of
      inflammation-associated colon cancer. Most infected mice develop mucinous
      adenocarcinoma (MUC) by 6 weeks post inoculation (PI); however, approximately one
      third do not progress to MUC. The ability to predict the development of MUC in
      mice used in therapeutic studies would confer a considerable saving of time and
      money. In addition, the inadvertent use of mice without MUC may confound
      therapeutic studies by making treatments seem falsely efficacious. We assessed
      both magnetic resonance imaging (MRI) and fecal biomarkers in Helicobacter- and
      sham-inoculated mice as methods of noninvasively detecting MUC before the
      predicted onset of disease. Non-contrast-enhanced MRI was able to detect lesions
      in 58% of mice with histologically confirmed MUC; however, serial imaging
      sessions produced inconsistent results. MRI was also a labor- and time-intensive
      technique requiring anesthesia. Alternatively, inflammatory biomarkers isolated
      from feces at early time points were correlated to later histologic lesions.
      Fecal expression of interleukin 1beta, macrophage inflammatory protein 1alpha,
      and regulated on activation, normal T-cell expressed, and secreted at 3 weeks PI
      correlated significantly with lesion severity at 9 weeks PI. For each biomarker,
      receiver-operator characteristic curves were also generated, and all three
      biomarkers performed well at 1 to 3 weeks PI, indicating that the development of
      MUC can be predicted based on the early expression of certain inflammatory
      mediators in feces.

PMID- 21170270
TI  - Surface expression of precursor N-cadherin promotes tumor cell invasion.
AB  - The expression of N-cadherin (NCAD) has been shown to correlate with increased
      tumor cell motility and metastasis. However, NCAD-mediated adhesion is a robust
      phenomenon and therefore seems to be inconsistent with the "release" from
      intercellular adhesion required for invasion. We show that in the most invasive
      melanoma and brain tumor cells, altered posttranslational processing results in
      abundant nonadhesive precursor N-cadherin (proNCAD) at the cell surface, although
      total NCAD levels remain constant. We demonstrate that aberrantly processed
      proNCAD promotes cell migration and invasion in vitro. Furthermore, in human
      tumor specimens, we find high levels of proNCAD as well, supporting an overall
      conclusion that proNCAD and mature NCAD coexist on these tumor cell surfaces and
      that it is the ratio between these functionally antagonistic moieties that
      directly correlates with invasion potential. Our work provides insight into what
      may be a widespread mechanism for invasion and metastasis and challenges the
      current dogma of the functional roles played by classic cadherins in tumor
      progression.

PMID- 21170272
TI  - Utility of in vivo transcription profiling for identifying Pseudomonas aeruginosa
      genes needed for gastrointestinal colonization and dissemination.
AB  - Microarray analysis of Pseudomonas aeruginosa mRNA transcripts expressed in vivo
      during animal infection has not been previously used to investigate potential
      virulence factors needed in this setting. We compared mRNA expression in
      bacterial cells recovered from the gastrointestinal (GI) tracts of P. aeruginosa
      colonized mice to that of P. aeruginosa in the drinking water used to colonize
      the mice. Genes associated with biofilm formation and type III secretion (T3SS)
      had markedly increased expression in the GI tract. A non-redundant transposon
      library in P. aeruginosa strain PA14 was used to test mutants in genes identified
      as having increased transcription during in vivo colonization. All of the Tn
      library mutants in biofilm-associated genes had an attenuated ability to form
      biofilms in vitro, but there were no significant differences in GI colonization
      and dissemination between these mutants and WT P. aeruginosa PA14. To evaluate
      T3SS factors, we tested GI colonization and neutropenia-induced dissemination of
      both deletional (PAO1 and PAK) and insertional (PA14) mutants in four genes in
      the P. aeruginosa T3SS, exoS or exoU, exoT, and popB. There were no significant
      differences in GI colonization among these mutant strains and their WT
      counterparts, whereas rates of survival following dissemination were
      significantly decreased in mice infected by the T3SS mutant strains. However,
      there was a variable, strain-dependent effect on overall survival between
      parental and T3SS mutants. Thus, increased transcription of genes during in vivo
      murine GI colonization is not predictive of an essential role for the gene
      product in either colonization or overall survival following induction of
      neutropenia.

PMID- 21170275
TI  - Fungal Infections After Liver Transplantation.

PMID- 21170273
TI  - Genome-wide screen for Mycobacterium tuberculosis genes that regulate host
      immunity.
AB  - In spite of its highly immunogenic properties, Mycobacterium tuberculosis (Mtb)
      establishes persistent infection in otherwise healthy individuals, making it one
      of the most widespread and deadly human pathogens. Mtb's prolonged survival may
      reflect production of microbial factors that prevent even more vigorous immunity
      (quantitative effect) or that divert the immune response to a non-sterilizing
      mode (qualitative effect). Disruption of Mtb genes has produced a list of several
      dozen candidate immunomodulatory factors. Here we used robotic fluorescence
      microscopy to screen 10,100 loss-of-function transposon mutants of Mtb for their
      impact on the expression of promoter-reporter constructs for 12 host immune
      response genes in a mouse macrophage cell line. The screen identified 364
      candidate immunoregulatory genes. To illustrate the utility of the candidate
      list, we confirmed the impact of 35 Mtb mutant strains on expression of
      endogenous immune response genes in primary macrophages. Detailed analysis
      focused on a strain of Mtb in which a transposon disrupts Rv0431, a gene encoding
      a conserved protein of unknown function. This mutant elicited much more
      macrophage TNFalpha, IL-12p40 and IL-6 in vitro than wild type Mtb, and was
      attenuated in the mouse. The mutant list provides a platform for exploring the
      immunobiology of tuberculosis, for example, by combining immunoregulatory
      mutations in a candidate vaccine strain.

PMID- 21170274
TI  - Identification of a common lupus disease-associated microRNA expression pattern
      in three different murine models of lupus.
AB  - BACKGROUND: Recent reports have shown that microRNAs (miRNAs) regulate vital
      immunological processes and have emerged as key regulators of immune system
      development and function. Therefore, it is important to determine miRNA
      dysregulation and its pathogenic contribution in autoimmune diseases, an aspect
      not adequately addressed thus far. METHODOLOGY/PRINCIPAL FINDINGS: In this study,
      we profiled miRNA expressions in splenic lymphocytes from three murine lupus
      models (MRL-lpr, B6-lpr and NZB/W(F1)) with different genetic background by miRNA
      microarray assays and Real-time RT-PCR. Despite the genetic differences among
      these three lupus stains, a common set of dysregulated miRNAs (miR-182-96-183
      cluster, miR-31, and miR-155) was identified in splenocytes when compared with
      age-matched control mice. The association of these miRNAs with the disease was
      highlighted by our observation that this miRNA expression pattern was evident in
      NZB/W mice only at an age when lupus disease is manifested. Further, we have
      shown that the miRNA dysregulation in MRL-lpr mice was not simply due to the
      activation of splenocytes. By Real-time RT-PCR, we confirmed that these miRNAs
      were upregulated in both purified splenic B and T cells from MRL-lpr mice. miR
      127 and miR-379, which were greatly upregulated in splenocytes from lpr mice,
      were moderately increased in diseased NZB/W mice. In addition, Real-time RT-PCR
      revealed that miR-146a, miR-101a, and miR-17-92 were also markedly upregulated in
      splenic T, but not B cells from MRL-lpr mice. CONCLUSIONS/SIGNIFICANCE: The
      identification of common lupus disease-associated miRNAs now forms the basis for
      the further investigation of the pathogenic contribution of these miRNAs in
      autoimmune lupus, which will advance our knowledge of the role of miRNAs in
      autoimmunity. Given that miRNAs are conserved, with regard to both evolution and
      function, our observation of a common lupus disease-associated miRNA expression
      pattern in murine lupus models is likely to have significant pathogenic,
      diagnostic, and/or therapeutic implications in human lupus.

PMID- 21170276
TI  - The Effect of the Civil War on Southern Marriage Patterns.

PMID- 21170277
TI  - Efficacy of anodal transcranial direct current stimulation (tDCS) for the
      treatment of fibromyalgia: results of a randomized, sham-controlled longitudinal
      clinical trial.
AB  - Fibromyalgia has been recognized as a central pain disorder with evidence of
      neuroanatomic and neurophysiologic alterations. Previous studies with techniques
      of noninvasive brain stimulation--transcranial direct current stimulation (tDCS)
      and repetitive transcranial magnetic stimulation (rTMS)--have shown that these
      methods are associated with a significant alleviation of fibromyalgia-associated
      pain and sleep dysfunction. Here we sought to determine whether a longer
      treatment protocol involving 10 sessions of 2 mA, 20 min tDCS of the left primary
      motor (M1) or dorsolateral prefrontal cortex (DLPFC) could offer additional, more
      long-lasting clinical benefits in the management of pain from fibromyalgia.
      METHODS: Forty-one women with chronic, medically refractory fibromyalgia were
      randomized to receive 10 daily sessions of M1, DLPFC, or sham tDCS. RESULTS: Our
      results show that M1 and DLPFC stimulation both display improvements in pain
      scores (VAS) and quality of life (FIQ) at the end of the treatment protocol, but
      only M1 stimulation resulted in long-lasting clinical benefits as assessed at 30
      and 60 days after the end of treatment. CONCLUSIONS: This study demonstrates the
      importance of the duration of the treatment period, suggesting that 10 daily
      sessions of tDCS result in more long lasting outcomes than only five sessions.
      Furthermore, this study supports the findings of a similarly designed rTMS trial
      as both induce pain reductions that are equally long-lasting.

PMID- 21170278
TI  - OKT3 and viral disease in pediatric liver transplant recipients.
AB  - Seventy-four consecutive pediatric liver transplant recipients were reviewed to
      assess the effect of the monoclonal anti-T-lymphocyte antibody OKT3 on subsequent
      viral infection (9 patients were excluded due to postoperative demise during the
      1st week). Twenty-two patients received OKT3 in addition to standard cyclosporine
      prednisone immunosuppression for either steroid-resistant acute rejection (18) or
      to facilitate reduction of cyclosporine due to severe renal impairment (4).
      Invasive infections were diagnosed by histology or culture in tissue biopsies or
      bronchoalveolar lavage specimens. The overall incidence of viral infection was
      58%, half of which was due to cytomegalovirus (CMV). Invasive viral disease was
      associated with increased mortality (37% vs. 3% p = 0.001). Viral-related deaths
      were due to CMV (5), disseminated adenovirus (3), disseminated enterovirus (1)
      and respiratory syncytial viral pneumonia (1). The use of OKT3 was associated
      with increased viral disease (59% vs. 33% p=0.04) and invasive primary CMV
      disease (58% vs. 19% p=0.04). Trends were observed toward increased overall viral
      infection (73% vs. 51 % p=0.08), primary CMV infection (58% vs. 25% p=0.08) and
      overall mortality (27% vs. 9% p =0.08) following OKT3 therapy. We conclude that
      pediatric liver transplant recipients who require OKT3 therapy may be at
      increased risk for invasive viral disease and especially invasive primary CMV
      disease.

PMID- 21170279
TI  - Pancreatic complications following orthotopic liver transplantation.
AB  - During fiscal year 1986, 40 out of 196 patients (21%) developed hyperamylasemia
      following orthotopic liver transplantation. The placement of a retropancreatic
      aortohepatic arterial interposition graft was associated with hyperamylasemia (p
      < 0.025). Eight patients (20%) developed clinically significant acute
      pancreatitis and its sequelae; abscesses and pseudocysts each in 2. Pancreatitis
      was attributable to the retropancreatic arterial graft in 4, viral infection in 2
      and obstruction of the pancreatic duct in 1 patient. All 4 patients with arterial
      graft-related pancreatitis exhibited poor graft function immediately
      postoperatively, of whom 2 required retransplantation - both of which failed to
      function. Five patients died (63%); 2 from primary graft non-function, 2 due to
      sepsis and 1 from systemic cytomegalovirus infection. We conclude that acute
      pancreatitis after liver transplantation is a life-threatening complication which
      is often associated with graft non-function.

PMID- 21170280
TI  - Smooth muscle tumor arising de novo in a liver allograft: A case report.

PMID- 21170281
TI  - Kidney after Extrarenal Transplantation - The Impact of Alemtuzumab Induction.

PMID- 21170282
TI  - The concept of depression as a dysfunction of the immune system.
AB  - Chronic stress, by initiating changes in the hypothalamic-pituitary-adrenal axis
      and the immune system, acts as a trigger for anxiety and depression. Both
      experimental and clinical evidence shows that a rise in the concentrations of
      proinflammatory cytokines and glucocorticoids, as occurs in chronically stressful
      situations and in depression, contribute to the behavioural changes associated
      with depression.A defect in serotonergic function is associated with
      hypercortisolaemia and the increase in proinflammatory cytokines that accompany
      depression. Glucocorticoids and proinflammatory cytokines enhance the conversion
      of tryptophan to kynurenine. In addition to the resulting decrease in the
      synthesis of brain serotonin, this leads to the formation of neurotoxins such as
      the glutamate agonist quinolinic acid and contributes to the increase in
      apoptosis of astrocytes, oligodendroglia and neurons.The importance of the
      inflammation hypothesis of depression lies in raising the possibility that
      psychotropic drugs that have a central anti-inflammatory action might provide a
      new generation of antidepressants.

PMID- 21170283
TI  - Sentactics(r): Computer-Automated Treatment of Underlying Forms.
AB  - BACKGROUND: Treatment of Underlying Forms (TUF) is a linguistically-based
      treatment for improving agrammatic sentence deficits, which enjoys a substantial
      database attesting to its efficacy for improving both sentence comprehension and
      production in agrammatic aphasia. However, TUF requires considerable linguistic
      background to administer and administration time can exceed the number of
      treatment sessions allotted in toto for reimbursement by third party payors in
      the United States. Thus, Sentactics(r), an interactive computer system that
      enables delivery of TUF by a virtual clinician was developed.  AIMS: This study
      tested the effects of Sentactics(r) on the acquisition and generalized production
      and comprehension of complex sentences. Additionally, a direct comparison of the
      results of computer-delivered Sentactics(r) and clinician-delivered TUF was
      undertaken.  METHODS #ENTITYSTARTX00026; PROCEDURES: Twelve agrammatic aphasic
      speakers participated in the study, with six receiving Sentactics(r) and six
      serving as experimental controls, who received no treatment. All participants
      were administered pre- and post-treatment sentence comprehension and production
      tests and other measures to evaluate the effects of Sentactics(r). Performance of
      the Sentactics(r) group also was compared to eight agrammatic patients who
      previously received clinician-delivered TUF treatment, identical to that
      delivered via Sentactics(r), but with a human clinician.  OUTCOMES
      #ENTITYSTARTX00026; RESULTS: Sentactics(r) significantly improved all six aphasic
      speakers' ability to comprehend and produce both trained and untrained,
      linguistically related, complex sentences as compared to six agrammatic control
      participants who did not receive Sentactics(r). In addition, comparing the
      results of the Sentactics(r) to clinician-delivered TUF revealed no significant
      differences between approaches with regard to acquisition or generalization
      patterns.  CONCLUSIONS: These data provide further support for the efficacy of
      TUF and demonstrate the viability of computer-delivered therapies in the field of
      aphasia treatment.

PMID- 21170284
TI  - Optoelectronic and Excitonic Properties of Oligoacenes: Substantial Improvements
      from Range-Separated Time-Dependent Density Functional Theory.
AB  - The optoelectronic and excitonic properties in a series of linear acenes
      (naphthalene up to heptacene) are investigated using range-separated methods
      within time-dependent density functional theory (TDDFT). In these rather simple
      systems, it is well-known that TDDFT methods using conventional hybrid
      functionals surprisingly fail in describing the low-lying L(a) and L(b) valence
      states, resulting in large, growing errors for the L(a) state and an incorrect
      energetic ordering as a function of molecular size. In this work, we demonstrate
      that the range-separated formalism largely eliminates both of these errors and
      also provides a consistent description of excitonic properties in these systems.
      We further demonstrate that reoptimizing the percentage of Hartree-Fock exchange
      in conventional hybrids to match wave function-based benchmark calculations still
      yields serious errors, and a full 100% Hartree-Fock range separation is essential
      for simultaneously describing both of the L(a) and L(b) transitions. From an
      analysis of electron-hole transition density matrices, we finally show that
      conventional hybrid functionals over-delocalize excitons and underestimate
      quasiparticle energy gaps in the acene systems. The results of our present study
      emphasize the importance of both a range-separated and asymptotically correct
      contribution of exchange in TDDFT for investigating optoelectronic and excitonic
      properties, even for these simple valence excitations.

PMID- 21170286
TI  - PHOTOCHEMICAL REACTION OF NITRO-POLYCYCLIC AROMATIC HYDROCARBONS: EFFECT BY
      SOLVENT AND STRUCTURE.
AB  - Photochemical degradation of 1-nitropyrene, 2-nitrofluorene, 2,7-dinitrofluorene,
      6-nitrochrysene, 3-nitrofluoranthene, 5-nitroacenaphthene, and 9-nitroanthracene
      were examined in CHCl(3), CH(2)Cl(2), DMF, DMF/H(2)O (80/20), CH(3)CN, or
      CH(3)CN/H(2)O (80/20). The degradation follows mostly the 1(st) order kinetics;
      but a few follow 2(nd) order kinetics or undergo self-catalysis. The
      photodegradation rates follow the order: CHCl(3) > CH(2)Cl(2) > DMF > DMF/H(2)O >
      CH(3)CN > CH(3)CN/H(2)O. DMF is an exceptional solvent because 3 of the 7
      compounds undergo self-catalytic reaction. 9-Nitroanthracene, which has a
      perpendicular nitro group, is the fastest, while the more compact 1-nitropyrene
      and 3-nitrofluoranthene, are the slowest degrading compounds.

PMID- 21170285
TI  - The Retirement Life Course in America at the Dawn of the Twenty-First Century.
AB  - As the baby boom cohorts expand the number of U.S. retirees, population estimates
      of the employment, withdrawal and reentry behaviors of older Americans' remain
      scarce. How long do people work? How frequently is retirement reversed? How many
      years are people retired? What is the modal age of retirement? And, how do the
      patterns for women compare to those for men? Using the 1992-2004 Health and
      Retirement Study, we estimate multistate working life tables to update
      information on the age-graded regularities of the retirement life course of men
      and women in the United States. We find that at age 50 men can expect to spend
      half of their remaining lives working for pay, while women can expect to spend
      just one-third. Half of all men and women have left the labor force by ages 63
      and 61, respectively. Although the majority of retirement exits are final,
      variation in the nature and duration of the retirement process is substantial, as
      about a third of men's and women's exits are reversed. By quantifying these
      patterns for men and women, we provide a sound empirical basis for evaluating
      policy designed to address the financial pressures population aging places on
      public and private pension systems.

PMID- 21170287
TI  - On the Bumpy Road to the Dominant Mode.
AB  - Maximum likelihood estimation in many classical statistical problems is beset by
      multimodality. This article explores several variations of deterministic
      annealing that tend to avoid inferior modes and find the dominant mode. In
      Bayesian settings, annealing can be tailored to find the dominant mode of the log
      posterior. Our annealing algorithms involve essentially trivial changes to
      existing optimization algorithms built on block relaxation or the EM or MM
      principle. Our examples include estimation with the multivariate t distribution,
      Gaussian mixture models, latent class analysis, factor analysis, multidimensional
      scaling and a one-way random effects model. In the numerical examples explored,
      the proposed annealing strategies significantly improve the chances for locating
      the global maximum.

PMID- 21170288
TI  - The Clinical Use of Human Culture-Expanded Autologous Bone Marrow Mesenchymal
      Stem Cells Transplanted on Platelet-Rich Fibrin Glue in the Treatment of
      Articular Cartilage Defects: A Pilot Study and Preliminary Results.
AB  - OBJECTIVE: To test the hypothesis that platelet-rich fibrin glue (PR-FG) can be
      used clinically as a scaffold to deliver autologous culture-expanded bone marrow
      mesenchymal stem cells (BM-MSCs) for cartilage repair and to report clinical
      results 1 y after implantation of MSCs PR-FG. PATIENTS AND METHODS: Autologous BM
      MSCs were culture expanded, placed on PR-FG intraoperatively, and then
      transplanted into 5 full-thickness cartilage defects of femoral condyles of 5
      patients and covered with an autologous periosteal flap. Patients were evaluated
      clinically at 6 and 12 mo by the Lysholm and Revised Hospital for Special Surgery
      Knee (RHSSK) scores and radiographically by x-rays and magnetic resonance imaging
      (MRI) at the same time points. Repair tissue in 2 patients was rated
      arthroscopically after 12 mo using the International Cartilage Repair Society
      (ICRS) Arthroscopic Score. STUDY DESIGN: Case series; level of evidence 4.
      RESULTS: All patients' symptoms improved over the follow-up period of 12 mo.
      Average Lysholm and RHSSK scores for all patients showed statistically
      significant improvement at 6 and 12 mo postoperatively (P < 0.05). There was no
      statistically significant difference between the 6 and 12 mo postoperative
      clinical scores (P = 0.18). ICRS arthroscopic scores were 8/12 and 11/12 (nearly
      normal) for the 2 patients who consented to arthroscopy. MRI of 3 patients at 12
      mo postoperatively revealed complete defect fill and complete surface congruity
      with native cartilage, whereas that of 2 patients showed incomplete congruity.
      CONCLUSION: Autologous BM-MSC transplantation on PR-FG as a cell scaffold may be
      an effective approach to promote the repair of articular cartilage defects of the
      knee in human patients.

PMID- 21170289
TI  - Myc Regulation of mRNA Cap Methylation.
AB  - The c-myc proto-oncogene regulates the expression of 15% to 20% of all genes,
      depending on the cell type, and the regulation is usually modest (1.5- to 2.0
      fold). The authors discovered that in addition to regulating mRNA abundance, c
      Myc regulates the formation of the 7-methylguanosine cap on many mRNAs, including
      transcriptional target genes and others not transcriptionally activated. Because
      the 7-methylguanosine cap is required for effective translation, enhanced methyl
      cap formation leads to increased protein production from Myc-responsive genes
      that exceeds the transcriptional induction. Increased cap methylation is linked
      to Myc-dependent enhanced activity of 2 critical kinases, TFIIH and p-TEFb, which
      phosphorylate the RNA polymerase II carboxy-terminal domain (CTD).
      Phosphorylation of the CTD recruits RNGTT and RNMT, the enzymes involved in mRNA
      capping, to the nascent transcript. Evidence is accumulating that enhanced cap
      methylation makes a significant contribution to Myc-dependent gene regulation and
      protein production.

PMID- 21170290
TI  - Kaposi's sarcoma in two primary liver allograft recipients occurring under FK506
      immunosuppression.
AB  - Of 1463 liver allograft recipients receiving the combination of FK506 and
      steroids as their primary immunosuppressive regimen, 2 patients developed
      Kaposi's sarcoma. Although previously described as a complication of organ
      transplantation, this is the first case report of Kaposi's sarcoma occurring in
      association with the macrolide immunosuppressive agent FK506. A discussion of the
      clinical presentation and course of Kaposi's sarcoma in these 2 patients, as well
      as a review of the past literature on Kaposi's sarcoma in organ transplant
      recipients, emphasizes the therapeutic difficulties encountered. Kaposi's sarcoma
      is also compared to lymphoproliferative disorders, another well-recognized
      complication of immunosuppression, highlighting the differences between these two
      entities.

PMID- 21170292
TI  - Discovering Structural Regularity in 3D Geometry.
AB  - We introduce a computational framework for discovering regular or repeated
      geometric structures in 3D shapes. We describe and classify possible regular
      structures and present an effective algorithm for detecting such repeated
      geometric patterns in point- or mesh-based models. Our method assumes no prior
      knowledge of the geometry or spatial location of the individual elements that
      define the pattern. Structure discovery is made possible by a careful analysis of
      pairwise similarity transformations that reveals prominent lattice structures in
      a suitable model of transformation space. We introduce an optimization method for
      detecting such uniform grids specifically designed to deal with outliers and
      missing elements. This yields a robust algorithm that successfully discovers
      complex regular structures amidst clutter, noise, and missing geometry. The
      accuracy of the extracted generating transformations is further improved using a
      novel simultaneous registration method in the spatial domain. We demonstrate the
      effectiveness of our algorithm on a variety of examples and show applications to
      compression, model repair, and geometry synthesis.

PMID- 21170291
TI  - MicroRNA-21 dysregulates the expression of MEF2C in neurons in monkey and human
      SIV/HIV neurological disease.
AB  - MicroRNAs (miRNAs) play important roles in regulating a plethora of physiological
      and pathophysiogical processes including neurodegeneration. In both HIV
      associated dementia in humans and its monkey model SIV encephalitis we find miR
      21, a miRNA largely known for its link to oncogenesis, to be significantly
      upregulated in the brain. In situ hybridization of the diseased brain sections
      revealed induction of miR-21 in neurons. MiR-21 can be induced in neurons by
      prolonged N-methyl-D-aspartic acid receptor stimulation, an excitotoxic process
      active in HIV and other neurodegenerative diseases. Introduction of miR-21 into
      human neurons leads to pathological functional defects. Furthermore, we show that
      miR-21 specifically targets the mRNA of myocyte enhancer factor 2C (MEF2C), a
      transcription factor crucial for neuronal function, and reduces its expression.
      MEF2C is dramatically downregulated in neurons of HIV-associated dementia
      patients as well as monkeys with SIVE. Together, this study elucidates a novel
      role for miR-21 in the brain, not only as a potential signature of neurological
      disease but also as a crucial effector of HIV induced neuronal dysfunction and
      neurodegeneration.

PMID- 21170294
TI  - Encapsulation of Capacitive Micromachined Ultrasonic Transducers Using
      Viscoelastic Polymer.
AB  - The packaging of a medical imaging or therapeutic ultrasound transducer should
      provide protective insulation while maintaining high performance. For a
      capacitive micromachined ultrasonic transducer (CMUT), an ideal encapsulation
      coating would therefore require a limited and predictable change on the static
      operation point and the dynamic performance, while insulating the high dc and dc
      actuation voltages from the environment. To fulfill these requirements,
      viscoelastic materials, such as polydimethylsiloxane (PDMS), were investigated
      for an encapsulation material. In addition, PDMS, with a glass-transition
      temperature below room temperature, provides a low Young's modulus that preserves
      the static behavior; at higher frequencies for ultrasonic operation, this
      material becomes stiffer and acoustically matches to water. In this paper, we
      demonstrate the modeling and implementation of the viscoelastic polymer as the
      encapsulation material. We introduce a finite element model (FEM) that addresses
      viscoelasticity. This enables us to correctly calculate both the static operation
      point and the dynamic behavior of the CMUT. CMUTs designed for medical imaging
      and therapeutic ultrasound were fabricated and encapsulated. Static and dynamic
      measurements were used to verify the FEM and show excellent agreement. This paper
      will help in the design process for optimizing the static and the dynamic
      behavior of viscoelastic-polymer-coated CMUTs.

PMID- 21170293
TI  - Pregnant women's responses to a tailored smoking cessation intervention: turning
      hopelessness into competence.
AB  - BACKGROUND: Cognitive behavioral interventions consisting of brief counseling and
      the provision of self-help material designed for pregnancy have been documented
      as effective smoking cessation interventions for pregnant women. However, there
      is a need to understand how such interventions are perceived by the targeted
      group. AIM: To understand the cognitive, emotional, and behavioral responses of
      pregnant women to a clinic-based smoking cessation intervention. METHODS: In
      depth interviews with women attending four antenatal clinics in Cape Town, South
      Africa, who were exposed to a smoking intervention delivered by midwives and peer
      counselors. Women were purposively selected to represent a variation in smoking
      behavior. Thirteen women were interviewed at their first antenatal visit and 10
      were followed up and reinterviewed later in their pregnancies. A content analysis
      approach was used, which resulted in categories and themes describing women's
      experiences, thoughts, and feelings about the intervention. RESULTS: Five women
      quit, five had cut down, and three could not be traced for follow-up. All
      informants perceived the intervention positively. Four main themes captured the
      intervention's role in influencing women's smoking behavior. The process started
      with 'understanding their reality,' which led to 'embracing change' and 'deciding
      to hold nothing back,' which created a basis for 'turning hopelessness into a
      feeling of competence.' CONCLUSION: The intervention succeeded in shifting women
      from feeling pessimistic about ever quitting to feeling encouraged to try and
      quit. Informants rated the social support they received very highly and expressed
      the need for the intervention to become a routine component of clinic services.

PMID- 21170295
TI  - Contribution of Primary Afferent Input to Trigeminal Astroglial Hyperactivity,
      Cytokine Induction and NMDA Receptor Phosphorylation.
AB  - We tested the hypothesis that primary afferent inputs play a role in astroglial
      hyperactivity after tissue injury. We first injected complete Freund's adjuvant
      (CFA, 0.05 ml, 1:1 oil/saline) into the masseter muscle, which upregulated glial
      fibrillary acidic protein (GFAP), a marker of astrocytes, interleukin (IL)-1beta
      an inflammatory cytokine, and phosphorylation of serine896 of the NR1 subunit (P
      NR1) of the NMDA receptor in the subnuclei interpolaris/caudalis (Vi/Vc)
      transition zone, an important structure for processing trigeminal nociceptive
      input. Local anesthetic block with lidocaine (2%) of the masseter muscle at 10
      min prior to injection of CFA into the same site significantly reduced the CFA
      induced increase in GFAP, IL-1beta and P-NR1 (p<0.05, n=4/group). We then tested
      the effect of peripheral electrical stimulation (ES). The ES protocol was burst
      stimulation consisting of trains of 4 square pulses (10-100 Hz, 0.1-3 mA, 0.5 ms
      pulse width). Under pentobarbital anesthesia, an ES was delivered every 0.2 s for
      a total of 30 min. The Vi/Vc tissues were processed for immunohistochemistry or
      western blot analysis at 10-120 min after ES. Compared to naive and SHAM-treated
      rats, there was increased immunoreactivity against GFAP, IL-1beta and P-NR1 in
      the Vi/Vc in rats receiving ES. Double staining showed that IL-1beta was
      selectively localized in GFAP-positive astroglia, and P-NR1-immunoreactivity was
      localized to neurons. These findings indicate that primary afferent inputs are
      necessary and sufficient to induce astroglial hyperactivity and upregulation of
      IL-1beta, as well as neuronal NMDA receptor phosphorylation.

PMID- 21170296
TI  - Listening to Filtered Music as a Treatment Option for Tinnitus: A Review.
AB  - TINNITUS IS THE PERCEPTION OF A SOUND IN THE absence of an external acoustic
      stimulus and it affects roughly 10-15% of the population. This review will
      discuss the different types of tinnitus and the current research on the
      underlying neural substrates of subjective tinnitus. Specific focus will be paid
      to the plasticity of the auditory cortex, the inputs from non-auditory centers in
      the central nervous system and how these are affected by tinnitus. We also will
      discuss several therapies that utilize music as a treatment for tinnitus and
      highlight a novel method that filters out the tinnitus frequency from the music,
      leveraging the plasticity in the auditory cortex as a means of reducing the
      impact of tinnitus.

PMID- 21170298
TI  - Ligand Binding Sensitivity of the Extracellular Loop Two of the Cannabinoid
      Receptor 1.
AB  - The cannabinoid receptor one (CB1) is a class A G-protein-coupled receptor
      thought to bind ligands primarily within its helical bundle. Evidence suggests,
      however, that the extracellular domain may also play a role. We have previously
      shown that the C-terminus of the extracellular loop 2 of CB1 is important in
      binding some compounds; receptors with mutations in this region (F268W, P269A,
      H270A, and I271A) bound some agonists with severely reduced affinity relative to
      the wild-type receptor. In the present work, we examine the impact of these
      mutations on binding a chemically diverse set of ligands. The receptors, F268W
      and I271A, exhibited a greater sensitivity to binding the inverse
      agonists/antagonists SLV319, AVE1625, NESS0327 relative to P269A and H270A,
      suggesting that the Pro and His are not involved in binding those compounds. In
      contrast, binding of the agonists, BAY593074 and WIN55212-2, was diminished in
      all four receptors, suggesting the conformational unit contributed by all four
      residues is important. A more marked loss in binding was observed for agonists of
      the nonclassical (CP55940) and classical (HU-210, JWH061, JWH179) cannabinoid
      classes and for a silent antagonist derivative (O-2050), pointing to the critical
      nature of this region for binding both the bicyclic/tricyclic core and the alkyl
      chain of these derivatives. However, moving the location of the alkyl chain on a
      series of pyrazole analogues shows it can be better accommodated in certain
      locations (O-1255) than others (O-1302, O-1690) and underscores the involvement
      of residues F268 and I271.

PMID- 21170297
TI  - Extensively Drug-Resistant Tuberculosis: A Sign of the Times and an Impetus for
      Antimicrobial Discovery.
AB  - Mycobacterium tuberculosis is an extraordinarily successful human pathogen,
      infecting one-third of the world's population and causing nearly two million
      deaths each year. In this article, current trends in worldwide tuberculosis (TB)
      incidence, prevalence, and mortality are discussed along with standard TB
      treatment regimens, characteristics of first-line and second-line anti
      tuberculosis drugs, and mechanisms of antibiotic resistance. The global TB
      emergency has been further exacerbated by extensively drug-resistant (XDR) TB
      strains that are resistant to our best antibiotics and very difficult to treat.
      This review also focuses on the emergence of XDR-TB strains, the global health
      impact, and existing treatment options and outcomes for XDR-TB disease. Finally,
      this review briefly describes new anti-tuberculosis drugs currently in Phase II
      clinical evaluations and the impetus for discovering new antibacterial compounds
      to target drug-resistant M. tuberculosis and improve tuberculosis therapy.

PMID- 21170299
TI  - Mesh-based Monte Carlo method using fast ray-tracing in Plucker coordinates.
AB  - We describe a fast mesh-based Monte Carlo (MC) photon migration algorithm for
      static and time-resolved imaging in 3D complex media. Compared with previous
      works using voxel-based media discretization, a mesh-based approach can be more
      accurate in modeling targets with curved boundaries or locally refined
      structures. We implement an efficient ray-tracing technique using Plucker
      Coordinates. The Barycentric coordinates computed from Plucker-formed ray-tracing
      enables us to use linear Lagrange basis functions to model both media properties
      and fluence distribution, leading to further improvement in accuracy. The Plucker
      coordinate ray-polygon intersection test can be extended to hexahedral or high
      order elements. Excellent agreement is found when comparing mesh-based MC with
      the analytical diffusion model and 3D voxel-based MC code in both homogeneous and
      heterogeneous cases. Realistic time-resolved imaging results are observed for a
      complex human brain anatomy using mesh-based MC. We also include multi-threading
      support in the software and will port it to a graphics processing unit platform
      in the near future.

PMID- 21170300
TI  - Regulation of herpesvirus lifecycle by viral microRNAs.
AB  - Human herpesviruses have latency and lytic replication phases in their lifecycle.
      Proper regulation of herpesviral lifecycle is essential for the evasion of host
      immune surveillance and development of their related diseases. Recent
      advancements indicate a role of a novel class of viral non-coding RNAs, microRNA
      (miRNA), in the fine-tuning of herpesviral lifecycle. So far, herpesviral miRNAs
      appear to promote viral latency by inhibiting viral lytic replication either
      through direct targeting of key viral replication genes or through manipulation
      of host pathways that regulate viral lifecycle. The oncogenic Kaposi sarcoma
      associated herpesvirus (KSHV) has adapted both strategies to control viral
      latency. Our recent study has identified a KSHV miRNA that inhibits viral lytic
      replication by upregulating the NFkappaB pathway.

PMID- 21170301
TI  - Histone deacetylases suppress CGG repeat-induced neurodegeneration via
      transcriptional silencing in models of fragile X tremor ataxia syndrome.
AB  - Fragile X Tremor Ataxia Syndrome (FXTAS) is a common inherited neurodegenerative
      disorder caused by expansion of a CGG trinucleotide repeat in the 5'UTR of the
      fragile X syndrome (FXS) gene, FMR1. The expanded CGG repeat is thought to induce
      toxicity as RNA, and in FXTAS patients mRNA levels for FMR1 are markedly
      increased. Despite the critical role of FMR1 mRNA in disease pathogenesis, the
      basis for the increase in FMR1 mRNA expression is unknown. Here we show that
      overexpressing any of three histone deacetylases (HDACs 3, 6, or 11) suppresses
      CGG repeat-induced neurodegeneration in a Drosophila model of FXTAS. This
      suppression results from selective transcriptional repression of the CGG repeat
      containing transgene. These findings led us to evaluate the acetylation state of
      histones at the human FMR1 locus. In patient-derived lymphoblasts and
      fibroblasts, we determined by chromatin immunoprecipitation that there is
      increased acetylation of histones at the FMR1 locus in pre-mutation carriers
      compared to control or FXS derived cell lines. These epigenetic changes correlate
      with elevated FMR1 mRNA expression in pre-mutation cell lines. Consistent with
      this finding, histone acetyltransferase (HAT) inhibitors repress FMR1 mRNA
      expression to control levels in pre-mutation carrier cell lines and extend
      lifespan in CGG repeat-expressing Drosophila. These findings support a disease
      model whereby the CGG repeat expansion in FXTAS promotes chromatin remodeling in
      cis, which in turn increases expression of the toxic FMR1 mRNA. Moreover, these
      results provide proof of principle that HAT inhibitors or HDAC activators might
      be used to selectively repress transcription at the FMR1 locus.

PMID- 21170302
TI  - CD4+ natural regulatory T cells prevent experimental cerebral malaria via CTLA-4
      when expanded in vivo.
AB  - Studies in malaria patients indicate that higher frequencies of peripheral blood
      CD4(+) Foxp3(+) CD25(+) regulatory T (Treg) cells correlate with increased blood
      parasitemia. This observation implies that Treg cells impair pathogen clearance
      and thus may be detrimental to the host during infection. In C57BL/6 mice
      infected with Plasmodium berghei ANKA, depletion of Foxp3(+) cells did not
      improve parasite control or disease outcome. In contrast, elevating frequencies
      of natural Treg cells in vivo using IL-2/anti-IL-2 complexes resulted in complete
      protection against severe disease. This protection was entirely dependent upon
      Foxp3(+) cells and resulted in lower parasite biomass, impaired antigen-specific
      CD4(+) T and CD8(+) T cell responses that would normally promote parasite tissue
      sequestration in this model, and reduced recruitment of conventional T cells to
      the brain. Furthermore, Foxp3(+) cell-mediated protection was dependent upon CTLA
      4 but not IL-10. These data show that T cell-mediated parasite tissue
      sequestration can be reduced by regulatory T cells in a mouse model of malaria,
      thereby limiting malaria-induced immune pathology.

PMID- 21170303
TI  - Inflammasome sensor Nlrp1b-dependent resistance to anthrax is mediated by caspase
      1, IL-1 signaling and neutrophil recruitment.
AB  - Bacillus anthracis infects hosts as a spore, germinates, and disseminates in its
      vegetative form. Production of anthrax lethal and edema toxins following
      bacterial outgrowth results in host death. Macrophages of inbred mouse strains
      are either sensitive or resistant to lethal toxin depending on whether they
      express the lethal toxin responsive or non-responsive alleles of the inflammasome
      sensor Nlrp1b (Nlrp1b(S/S) or Nlrp1b(R/R), respectively). In this study, Nlrp1b
      was shown to affect mouse susceptibility to infection. Inbred and congenic mice
      harboring macrophage-sensitizing Nlrp1b(S/S) alleles (which allow activation of
      caspase-1 and IL-1beta release in response to anthrax lethal toxin challenge)
      effectively controlled bacterial growth and dissemination when compared to mice
      having Nlrp1b(R/R) alleles (which cannot activate caspase-1 in response to
      toxin). Nlrp1b(S)-mediated resistance to infection was not dependent on the route
      of infection and was observed when bacteria were introduced by either
      subcutaneous or intravenous routes. Resistance did not occur through alterations
      in spore germination, as vegetative bacteria were also killed in Nlrp1b(S/S)
      mice. Resistance to infection required the actions of both caspase-1 and IL-1beta
      as Nlrp1b(S/S) mice deleted of caspase-1 or the IL-1 receptor, or treated with
      the Il-1 receptor antagonist anakinra, were sensitized to infection. Comparison
      of circulating neutrophil levels and IL-1beta responses in Nlrp1b(S/S),Nlrp1b(R/)
      (R) and IL-1 receptor knockout mice implicated Nlrp1b and IL-1 signaling in
      control of neutrophil responses to anthrax infection. Neutrophil depletion
      experiments verified the importance of this cell type in resistance to B.
      anthracis infection. These data confirm an inverse relationship between murine
      macrophage sensitivity to lethal toxin and mouse susceptibility to spore
      infection, and establish roles for Nlrp1b(S), caspase-1, and IL-1beta in
      countering anthrax infection.

PMID- 21170304
TI  - Genome-wide interrogation of Mammalian stem cell fate determinants by nested
      chromosome deletions.
AB  - Understanding the function of important DNA elements in mammalian stem cell
      genomes would be enhanced by the availability of deletion collections in which
      segmental haploidies are precisely characterized. Using a modified Cre-loxP-based
      system, we now report the creation and characterization of a collection of ~1,300
      independent embryonic stem cell (ESC) clones enriched for nested chromosomal
      deletions. Mapping experiments indicate that this collection spans over 25% of
      the mouse genome with good representative coverage of protein-coding genes,
      regulatory RNAs, and other non-coding sequences. This collection of clones was
      screened for in vitro defects in differentiation of ESC into embryoid bodies
      (EB). Several putative novel haploinsufficient regions, critical for EB
      development, were identified. Functional characterization of one of these
      regions, through BAC complementation, identified the ribosomal gene Rps14 as a
      novel haploinsufficient determinant of embryoid body formation. This new library
      of chromosomal deletions in ESC (DelES: http://bioinfo.iric.ca/deles) will serve
      as a unique resource for elucidation of novel protein-coding and non-coding
      regulators of ESC activity.

PMID- 21170305
TI  - Investigation and functional characterization of rare genetic variants in the
      adipose triglyceride lipase in a large healthy working population.
AB  - Recent studies demonstrated a strong influence of rare genetic variants on
      several lipid-related traits. However, their impact on free fatty acid (FFA)
      plasma concentrations, as well as the role of rare variants in a general
      population, has not yet been thoroughly addressed. The adipose triglyceride
      lipase (ATGL) is encoded by the PNPLA2 gene and catalyzes the rate-limiting step
      of lipolysis. It represents a prominent candidate gene affecting FFA
      concentrations. We therefore screened the full genomic region of ATGL for
      mutations in 1,473 randomly selected individuals from the SAPHIR (Salzburg
      Atherosclerosis Prevention program in subjects at High Individual Risk) Study
      using a combined Ecotilling and sequencing approach and functionally investigated
      all detected protein variants by in-vitro studies. We observed 55 novel mostly
      rare genetic variants in this general population sample. Biochemical evaluation
      of all non-synonymous variants demonstrated the presence of several mutated but
      mostly still functional ATGL alleles with largely varying residual lipolytic
      activity. About one-quarter (3 out of 13) of the investigated variants presented
      a marked decrease or total loss of catalytic function. Genetic association
      studies using both continuous and dichotomous approaches showed a shift towards
      lower plasma FFA concentrations for rare variant carriers and an accumulation of
      variants in the lower 10%-quantile of the FFA distribution. However, the
      generally rather small effects suggest either only a secondary role of rare ATGL
      variants on the FFA levels in the SAPHIR population or a recessive action of ATGL
      variants. In contrast to these rather small effects, we describe here also the
      first patient with "neutral lipid storage disease with myopathy" (NLSDM) with a
      point mutation in the catalytic dyad, but otherwise intact protein.

PMID- 21170306
TI  - High-efficient generation of induced pluripotent stem cells from human
      astrocytes.
AB  - The reprogramming of human somatic cells to induced pluripotent stem (hiPS) cells
      enables the possibility of generating patient-specific autologous cells for
      regenerative medicine. A number of human somatic cell types have been reported to
      generate hiPS cells, including fibroblasts, keratinocytes and peripheral blood
      cells, with variable reprogramming efficiencies and kinetics. Here, we show that
      human astrocytes can also be reprogrammed into hiPS (ASThiPS) cells, with similar
      efficiencies to keratinocytes, which are currently reported to have one of the
      highest somatic reprogramming efficiencies. ASThiPS lines were indistinguishable
      from human embryonic stem (ES) cells based on the expression of pluripotent
      markers and the ability to differentiate into the three embryonic germ layers in
      vitro by embryoid body generation and in vivo by teratoma formation after
      injection into immunodeficient mice. Our data demonstrates that a human
      differentiated neural cell type can be reprogrammed to pluripotency and is
      consistent with the universality of the somatic reprogramming procedure.

PMID- 21170307
TI  - Continuous and periodic expansion of CAG repeats in Huntington's disease R6/1
      mice.
AB  - Huntington's disease (HD) is one of several neurodegenerative disorders caused by
      expansion of CAG repeats in a coding gene. Somatic CAG expansion rates in HD vary
      between organs, and the greatest instability is observed in the brain,
      correlating with neuropathology. The fundamental mechanisms of somatic CAG repeat
      instability are poorly understood, but locally formed secondary DNA structures
      generated during replication and/or repair are believed to underlie triplet
      repeat expansion. Recent studies in HD mice have demonstrated that mismatch
      repair (MMR) and base excision repair (BER) proteins are expansion inducing
      components in brain tissues. This study was designed to simultaneously
      investigate the rates and modes of expansion in different tissues of HD R6/1 mice
      in order to further understand the expansion mechanisms in vivo. We demonstrate
      continuous small expansions in most somatic tissues (exemplified by tail), which
      bear the signature of many short, probably single-repeat expansions and
      contractions occurring over time. In contrast, striatum and cortex display a
      dramatic--and apparently irreversible--periodic expansion. Expansion profiles
      displaying this kind of periodicity in the expansion process have not previously
      been reported. These in vivo findings imply that mechanistically distinct
      expansion processes occur in different tissues.

PMID- 21170308
TI  - The EpsE flagellar clutch is bifunctional and synergizes with EPS biosynthesis to
      promote Bacillus subtilis biofilm formation.
AB  - Many bacteria inhibit motility concomitant with the synthesis of an extracellular
      polysaccharide matrix and the formation of biofilm aggregates. In Bacillus
      subtilis biofilms, motility is inhibited by EpsE, which acts as a clutch on the
      flagella rotor to inhibit motility, and which is encoded within the 15 gene eps
      operon required for EPS production. EpsE shows sequence similarity to the
      glycosyltransferase family of enzymes, and we demonstrate that the conserved
      active site motif is required for EPS biosynthesis. We also screen for residues
      specifically required for either clutch or enzymatic activity and demonstrate
      that the two functions are genetically separable. Finally, we show that, whereas
      EPS synthesis activity is dominant for biofilm formation, both functions of EpsE
      synergize to stabilize cell aggregates and relieve selective pressure to abolish
      motility by genetic mutation. Thus, the transition from motility to biofilm
      formation may be governed by a single bifunctional enzyme.

PMID- 21170309
TI  - A scalable approach for discovering conserved active subnetworks across species.
AB  - Overlaying differential changes in gene expression on protein interaction
      networks has proven to be a useful approach to interpreting the cell's dynamic
      response to a changing environment. Despite successes in finding active
      subnetworks in the context of a single species, the idea of overlaying lists of
      differentially expressed genes on networks has not yet been extended to support
      the analysis of multiple species' interaction networks. To address this problem,
      we designed a scalable, cross-species network search algorithm, neXus (Network
      cross(X)-species-Search), that discovers conserved, active subnetworks based on
      parallel differential expression studies in multiple species. Our approach
      leverages functional linkage networks, which provide more comprehensive coverage
      of functional relationships than physical interaction networks by combining
      heterogeneous types of genomic data. We applied our cross-species approach to
      identify conserved modules that are differentially active in stem cells relative
      to differentiated cells based on parallel gene expression studies and functional
      linkage networks from mouse and human. We find hundreds of conserved active
      subnetworks enriched for stem cell-associated functions such as cell cycle, DNA
      repair, and chromatin modification processes. Using a variation of this approach,
      we also find a number of species-specific networks, which likely reflect
      mechanisms of stem cell function that have diverged between mouse and human. We
      assess the statistical significance of the subnetworks by comparing them with
      subnetworks discovered on random permutations of the differential expression
      data. We also describe several case examples that illustrate the utility of
      comparative analysis of active subnetworks.

PMID- 21170310
TI  - GC-rich sequence elements recruit PRC2 in mammalian ES cells.
AB  - Polycomb proteins are epigenetic regulators that localize to developmental loci
      in the early embryo where they mediate lineage-specific gene repression. In
      Drosophila, these repressors are recruited to sequence elements by DNA binding
      proteins associated with Polycomb repressive complex 2 (PRC2). However, the
      sequences that recruit PRC2 in mammalian cells have remained obscure. To address
      this, we integrated a series of engineered bacterial artificial chromosomes into
      embryonic stem (ES) cells and examined their chromatin. We found that a 44 kb
      region corresponding to the Zfpm2 locus initiates de novo recruitment of PRC2. We
      then pinpointed a CpG island within this locus as both necessary and sufficient
      for PRC2 recruitment. Based on this causal demonstration and prior genomic
      analyses, we hypothesized that large GC-rich elements depleted of activating
      transcription factor motifs mediate PRC2 recruitment in mammals. We validated
      this model in two ways. First, we showed that a constitutively active CpG island
      is able to recruit PRC2 after excision of a cluster of activating motifs. Second,
      we showed that two 1 kb sequence intervals from the Escherichia coli genome with
      GC-contents comparable to a mammalian CpG island are both capable of recruiting
      PRC2 when integrated into the ES cell genome. Our findings demonstrate a causal
      role for GC-rich sequences in PRC2 recruitment and implicate a specific subset of
      CpG islands depleted of activating motifs as instrumental for the initial
      localization of this key regulator in mammalian genomes.

PMID- 21170312
TI  - A minimal model of metabolism-based chemotaxis.
AB  - Since the pioneering work by Julius Adler in the 1960's, bacterial chemotaxis has
      been predominantly studied as metabolism-independent. All available simulation
      models of bacterial chemotaxis endorse this assumption. Recent studies have
      shown, however, that many metabolism-dependent chemotactic patterns occur in
      bacteria. We hereby present the simplest artificial protocell model capable of
      performing metabolism-based chemotaxis. The model serves as a proof of concept to
      show how even the simplest metabolism can sustain chemotactic patterns of varying
      sophistication. It also reproduces a set of phenomena that have recently
      attracted attention on bacterial chemotaxis and provides insights about
      alternative mechanisms that could instantiate them. We conclude that relaxing the
      metabolism-independent assumption provides important theoretical advances, forces
      us to rethink some established pre-conceptions and may help us better understand
      unexplored and poorly understood aspects of bacterial chemotaxis.

PMID- 21170313
TI  - A longitudinal study of medicaid coverage for tobacco dependence treatments in
      Massachusetts and associated decreases in hospitalizations for cardiovascular
      disease.
AB  - BACKGROUND: Insurance coverage of tobacco cessation medications increases their
      use and reduces smoking prevalence in a population. However, uncertainty about
      the impact of this coverage on health care utilization and costs is a barrier to
      the broader adoption of this policy, especially by publicly funded state Medicaid
      insurance programs. Whether a publicly funded tobacco cessation benefit leads to
      decreased medical claims for tobacco-related diseases has not been studied. We
      examined the experience of Massachusetts, whose Medicaid program adopted
      comprehensive coverage of tobacco cessation medications in July 2006. Over 75,000
      Medicaid subscribers used the benefit in the first 2.5 years. On the basis of
      earlier secondary survey work, it was estimated that smoking prevalence declined
      among subscribers by 10% during this period. METHODS AND FINDINGS: Using claims
      data, we compared the probability of hospitalization prior to use of the tobacco
      cessation pharmacotherapy benefit with the probability of hospitalization after
      benefit use among Massachusetts Medicaid beneficiaries, adjusting for
      demographics, comorbidities, seasonality, influenza cases, and the implementation
      of the statewide smoke-free air law using generalized estimating equations.
      Statistically significant annualized declines of 46% (95% confidence interval 2%
      70%) and 49% (95% confidence interval 6%-72%) were observed in hospital
      admissions for acute myocardial infarction and other acute coronary heart disease
      diagnoses, respectively. There were no significant decreases in hospitalizations
      rates for respiratory diagnoses or seven other diagnostic groups evaluated.
      CONCLUSIONS: Among Massachusetts Medicaid subscribers, use of a comprehensive
      tobacco cessation pharmacotherapy benefit was associated with a significant
      decrease in claims for hospitalizations for acute myocardial infarction and acute
      coronary heart disease, but no significant change in hospital claims for other
      diagnoses. For low-income smokers, removing the barriers to the use of smoking
      cessation pharmacotherapy has the potential to decrease short-term utilization of
      hospital services.

PMID- 21170314
TI  - Phenocopy--a strategy to qualify chemical compounds during hit-to-lead and/or
      lead optimization.
AB  - A phenocopy is defined as an environmentally induced phenotype of one individual
      which is identical to the genotype-determined phenotype of another individual.
      The phenocopy phenomenon has been translated to the drug discovery process as
      phenotypes produced by the treatment of biological systems with new chemical
      entities (NCE) may resemble environmentally induced phenotypic modifications.
      Various new chemical entities exerting inhibition of the kinase activity of
      Transforming Growth Factor beta Receptor I (TGF-betaR1) were qualified by high
      throughput RNA expression profiling. This chemical genomics approach resulted in
      a precise time-dependent insight to the TGF-beta biology and allowed furthermore
      a comprehensive analysis of each NCE's off-target effects. The evaluation of off
      target effects by the phenocopy approach allows a more accurate and integrated
      view on optimized compounds, supplementing classical biological evaluation
      parameters such as potency and selectivity. It has therefore the potential to
      become a novel method for ranking compounds during various drug discovery phases.

PMID- 21170315
TI  - Dissociated mechanisms of extracting perceptual information into visual working
      memory.
AB  - BACKGROUND: The processing mechanisms of visual working memory (VWM) have been
      extensively explored in the recent decade. However, how the perceptual
      information is extracted into VWM remains largely unclear. The current study
      investigated this issue by testing whether the perceptual information was
      extracted into VWM via an integrated-object manner so that all the irrelevant
      information would be extracted (object hypothesis), or via a feature-based manner
      so that only the target-relevant information would be extracted (feature
      hypothesis), or via an analogous processing manner as that in visual perception
      (analogy hypothesis). METHODOLOGY/PRINCIPAL FINDINGS: High-discriminable
      information which is processed at the parallel stage of visual perception and
      fine-grained information which is processed via focal attention were selected as
      the representatives of perceptual information. The analogy hypothesis predicted
      that whereas high-discriminable information is extracted into VWM automatically,
      fine-grained information will be extracted only if it is task-relevant. By
      manipulating the information type of the irrelevant dimension in a change
      detection task, we found that the performance was affected and the ERP component
      N270 was enhanced if a change between the probe and the memorized stimulus
      consisted of irrelevant high-discriminable information, but not if it consisted
      of irrelevant fine-grained information. CONCLUSIONS/SIGNIFICANCE: We conclude
      that dissociated extraction mechanisms exist in VWM for information resolved via
      dissociated processes in visual perception (at least for the information tested
      in the current study), supporting the analogy hypothesis.

PMID- 21170316
TI  - Natural proteasome inhibitor celastrol suppresses androgen-independent prostate
      cancer progression by modulating apoptotic proteins and NF-kappaB.
AB  - BACKGROUND: Celastrol is a natural proteasome inhibitor that exhibits promising
      anti-tumor effects in human malignancies, especially the androgen-independent
      prostate cancer (AIPC) with constitutive NF-kappaB activation. Celastrol induces
      apoptosis by means of proteasome inhibition and suppresses prostate tumor growth.
      However, the detailed mechanism of action remains elusive. In the current study,
      we aim to test the hypothesis that celastrol suppresses AIPC progression via
      inhibiting the constitutive NF-kappaB activity as well as modulating the Bcl-2
      family proteins. METHODOLOGY/PRINCIPAL FINDINGS: We examined the efficacy of
      celastrol both in vitro and in vivo, and evaluated the role of NF-kappaB in
      celastrol-mediated AIPC regression. We found that celastrol inhibited cell
      proliferation in all three AIPC cell lines (PC-3, DU145 and CL1), with IC50 in
      the range of 1-2 uM. Celastrol also suppressed cell migration and invasion.
      Celastrol significantly induced apoptosis as evidenced by increased sub-G1
      population, caspase activation and PARP cleavage. Moreover, celastrol promoted
      cleavage of the anti-apoptotic protein Mcl-1 and activated the pro-apoptotic
      protein Noxa. In addition, celastrol rapidly blocked cytosolic IkappaBalpha
      degradation and nuclear translocation of RelA. Likewise, celastrol inhibited the
      expression of multiple NF-kappaB target genes that are involved in proliferation,
      invasion and anti-apoptosis. Celastrol suppressed AIPC tumor progression by
      inhibiting proliferation, increasing apoptosis and decreasing angiogenesis, in PC
      3 xenograft model in nude mouse. Furthermore, increased cellular IkappaBalpha and
      inhibited expression of various NF-kappaB target genes were observed in tumor
      tissues. CONCLUSIONS/SIGNIFICANCE: Our data suggest that, via targeting the
      proteasome, celastrol suppresses proliferation, invasion and angiogenesis by
      inducing the apoptotic machinery and attenuating constitutive NF-kappaB activity
      in AIPC both in vitro and in vivo. Celastrol as an active ingredient of
      traditional herbal medicine could thus be developed as a new therapeutic agent
      for hormone-refractory prostate cancer.

PMID- 21170317
TI  - Fluorescent protein-based methods for on-plate screening of gene insertion.
AB  - BACKGROUND: Unlike the commonly used method of blue-white screening for gene
      insertion, a fluorescent protein-based screening method offers a gain-of-function
      screening process without using any co-factors and a gene fusion product with a
      fluorescent protein reporter that is further useful in cell imaging studies.
      However, complications related to protein-folding efficiencies of the gene insert
      in fusion with fluorescent protein reporters prevent effective on-plate bacterial
      colony selection leading to its limited use. METHODOLOGY/PRINCIPAL FINDINGS:
      Here, we present three methods to tackle this problem. Our first method promotes
      the folding of the gene insert by using an N-terminal protein such as calmodulin
      that is well folded and expressed. Under this method, fluorescence was increased
      more than 30x over control allowing for enhanced screening. Our second method
      creates a fluorescent protein that is N-terminal to the gene upon insertion,
      thereby reducing the dependency of the fluorescent protein reporter on the
      folding of the gene insert. Our third method eliminates any dependence of the
      fluorescent protein reporter on the folding of the gene insert by using a stop
      and start sequence for protein translation. CONCLUSIONS/SIGNIFICANCE: The three
      methods together will expand the usefulness of fluorescence on-plate screening
      and offer a powerful alternative to blue-white screening.

PMID- 21170318
TI  - Nuclear shield: a multi-enzyme task-force for nucleus protection.
AB  - BACKGROUND: In eukaryotic cells the nuclear envelope isolates and protects DNA
      from molecules that could damage its structure or interfere with its processing.
      Moreover, selected protection enzymes and vitamins act as efficient guardians
      against toxic compounds both in the nucleoplasm and in the cytosol. The
      observation that a cytosolic detoxifying and antioxidant enzyme i.e. glutathione
      transferase is accumulated in the perinuclear region of the rat hepatocytes
      suggests that other unrecognized modalities of nuclear protection may exist. Here
      we show evidence for the existence of a safeguard enzyme machinery formed by an
      hyper-crowding of cationic enzymes and proteins encompassing the nuclear membrane
      and promoted by electrostatic interactions. METHODOLOGY/PRINCIPAL FINDINGS:
      Electron spectroscopic imaging, zeta potential measurements, isoelectrofocusing,
      comet assay and mass spectrometry have been used to characterize this surprising
      structure that is present in the cells of all rat tissues examined (liver,
      kidney, heart, lung and brain), and that behaves as a "nuclear shield". In
      hepatocytes, this hyper-crowding structure is about 300 nm thick, it is mainly
      formed by cationic enzymes and the local concentration of key protection enzymes,
      such as glutathione transferase, catalase and glutathione peroxidase is up to
      seven times higher than in the cytosol. The catalytic activity of these enzymes,
      when packed in the shield, is not modified and their relative concentrations vary
      remarkably in different tissues. Removal of this protective shield renders
      chromosomes more sensitive to damage by oxidative stress. Specific nuclear
      proteins anchored to the outer nuclear envelope are likely involved in the shield
      formation and stabilization. CONCLUSIONS/SIGNIFICANCE: The characterization of
      this previously unrecognized nuclear shield in different tissues opens a new
      interesting scenario for physiological and protection processes in eukaryotic
      cells. Selection and accumulation of protection enzymes near sensitive targets
      represents a new safeguard modality which deeply differs from the adaptive
      response which is based on expression of specific enzymes.

PMID- 21170319
TI  - DNA aptamers as molecular probes for colorectal cancer study.
AB  - BACKGROUND: Understanding the molecular features of specific tumors can increase
      our knowledge about the mechanism(s) underlying disease development and
      progression. This is particularly significant for colorectal cancer, which is a
      heterogeneous complex of diseases developed in a sequential manner through a
      multistep carcinogenic process. As such, it is likely that tumors with similar
      characteristics might originate in the same manner and have a similar molecular
      behavior. Therefore, specific mapping of the molecular features can be
      potentially useful for both tumor classification and the development of
      appropriate therapeutic regimens. However, this can only be accomplished by
      developing high-affinity molecular probes with the ability to recognize specific
      markers associated with different tumors. Aptamers can most easily meet this
      challenge based on their target diversity, flexible manipulation and ease of
      development. METHODOLOGY AND RESULTS: Using a method known as cell-based
      Systematic Evolution of Ligands by Exponential enrichment (cell-SELEX) and
      colorectal cancer cultured cell lines DLD-1 and HCT 116, we selected a panel of
      target-specific aptamers. Binding studies by flow cytometry and confocal
      microscopy showed that these aptamers have high affinity and selectivity. Our
      data further show that these aptamers neither recognize normal colon cells
      (cultured and fresh), nor do they recognize most other cancer cell lines tested.
      CONCLUSION/SIGNIFICANCE: The selected aptamers can identify specific biomarkers
      associated with colorectal cancers. We believe that these probes could be further
      developed for early disease detection, as well as prognostic markers, of
      colorectal cancers.

PMID- 21170320
TI  - Environmental Profile of a Community's Health (EPOCH): an instrument to measure
      environmental determinants of cardiovascular health in five countries.
AB  - BACKGROUND: The environment in which people live is known to be important in
      influencing diet, physical activity, smoking, psychosocial and other risk factors
      for cardiovascular (CV) disease. However no instrument exists that evaluates
      communities for these multiple environmental factors and is suitable for use
      across different communities, regions and countries. This report describes the
      design and reliability of an instrument to measure environmental determinants of
      CV risk factors. METHOD/PRINCIPAL FINDINGS: THE ENVIRONMENTAL PROFILE OF
      COMMUNITY HEALTH (EPOCH) INSTRUMENT COMPRISES TWO PARTS: (I) an assessment of the
      physical environment, and (II) an interviewer-administered questionnaire to
      collect residents' perceptions of their community. We examined the inter-rater
      reliability amongst 3 observers from each region of the direct observation
      component of the instrument (EPOCH I) in 93 rural and urban communities in 5
      countries (Canada, Colombia, Brazil, China and India). Data collection using the
      EPOCH instrument was feasible in all communities. Reliability of the instrument
      was excellent (Intraclass Correlation Coefficient--ICC>0.75) for 24 of 38 items
      and fair to good (ICC 0.4-0.75) for 14 of 38 items. CONCLUSION: This report shows
      data collection with the EPOCH instrument is feasible and direct observation of
      community measures reliable. The EPOCH instrument will enable further research on
      environmental determinants of health for population studies from a broad range of
      settings.

PMID- 21170321
TI  - Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and
      type 2 diabetic obese African-American women.
AB  - Insulin resistance progressing to type 2 diabetes mellitus (T2DM) is marked by a
      broad perturbation of macronutrient intermediary metabolism. Understanding the
      biochemical networks that underlie metabolic homeostasis and how they associate
      with insulin action will help unravel diabetes etiology and should foster
      discovery of new biomarkers of disease risk and severity. We examined differences
      in plasma concentrations of >350 metabolites in fasted obese T2DM vs. obese non
      diabetic African-American women, and utilized principal components analysis to
      identify 158 metabolite components that strongly correlated with fasting HbA1c
      over a broad range of the latter (r = -0.631; p<0.0001). In addition to many
      unidentified small molecules, specific metabolites that were increased
      significantly in T2DM subjects included certain amino acids and their derivatives
      (i.e., leucine, 2-ketoisocaproate, valine, cystine, histidine), 2
      hydroxybutanoate, long-chain fatty acids, and carbohydrate derivatives. Leucine
      and valine concentrations rose with increasing HbA1c, and significantly
      correlated with plasma acetylcarnitine concentrations. It is hypothesized that
      this reflects a close link between abnormalities in glucose homeostasis, amino
      acid catabolism, and efficiency of fuel combustion in the tricarboxylic acid
      (TCA) cycle. It is speculated that a mechanism for potential TCA cycle
      inefficiency concurrent with insulin resistance is "anaplerotic stress" emanating
      from reduced amino acid-derived carbon flux to TCA cycle intermediates, which if
      coupled to perturbation in cataplerosis would lead to net reduction in TCA cycle
      capacity relative to fuel delivery.

PMID- 21170322
TI  - Transmitted drug resistance in persons with acute/early HIV-1 in San Francisco,
      2002-2009.
AB  - BACKGROUND: Transmitted HIV-1 drug resistance (TDR) is an ongoing public health
      problem, representing 10-20% of new HIV infections in many geographic areas. TDR
      usually arises from two main sources: individuals on antiretroviral therapy (ART)
      who are failing to achieve virologic suppression, and individuals who acquired
      TDR and transmit it while still ART-naive. TDR rates can be impacted when novel
      antiretroviral medications are introduced that allow for greater virologic
      suppression of source patients. Although several new HIV medications were
      introduced starting in late 2007, including raltegravir, maraviroc, and
      etravirine, it is not known whether the prevalence of TDR was subsequently
      affected in 2008-2009. METHODOLOGY/PRINCIPAL FINDINGS: We performed population
      sequence genotyping on individuals who were diagnosed with acute or early HIV (<6
      months duration) and who enrolled in the Options Project, a prospective cohort,
      between 2002 and 2009. We used logistic regression to compare the odds of
      acquiring drug-resistant HIV before versus after the arrival of new ART (2005
      2007 vs. 2008-2009). From 2003-2007, TDR rose from 7% to 24%. Prevalence of TDR
      was then 15% in 2008 and in 2009. While the odds of acquiring TDR were lower in
      2008-2009 compared to 2005-2007, this was not statistically significant (odds
      ratio 0.65, 95% CI 0.31-1.38; p = 0.27). CONCLUSIONS: Our study suggests that
      transmitted drug resistance rose from 2003-2007, but this upward trend did not
      continue in 2008 and 2009. Nevertheless, the TDR prevalence in 2008-2009 remained
      substantial, emphasizing that improved management strategies for drug-resistant
      HIV are needed if TDR is to be further reduced. Continued surveillance for TDR
      will be important in understanding the full impact of new antiretroviral
      medications.

PMID- 21170323
TI  - Aromatase gene polymorphisms are associated with survival among patients with
      cardiovascular disease in a sex-specific manner.
AB  - INTRODUCTION: CYP19A1 encodes aromatase, the enzyme responsible for the
      conversion of androgens to estrogens, and may play a role in variation in
      outcomes among men and women with cardiovascular disease. We sought to examine
      genetic variation in CYP19A1 for its potential role in sex differences in
      cardiovascular disease outcomes. METHODS: Caucasian individuals from two
      independent populations were assessed: 1) a prospective cohort of patients with
      acute coronary syndromes with 3-year mortality follow-up (n = 568) and 2) a
      nested case-control study from a randomized, controlled trial of hypertension
      patients with stable coronary disease in which the primary outcome was death,
      nonfatal myocardial infarction (MI) or nonfatal stroke (n = 619). Six CYP19A1
      SNPs were genotyped (-81371 C>T, -45965 G>C, M201T, R264C, 80 A>G, and +32226
      G>A). The sex*genotype interaction term was assessed for the primary outcome and
      compared by genotype in men and women when a significant interaction term was
      identified. RESULTS: We identified a significant interaction between -81371 C>T
      and sex (p = 0.025) in the ACS population. The variant allele was associated with
      a 78% increase in mortality in men (HR 1.78, 95% confidence interval [CI] 1.08
      2.94) and a nonsignificant 42% decrease in mortality among women (HR 0.58, 95% CI
      0.22-1.54). We identified a similar association in the hypertensive CAD group,
      the -81371 C>T*sex interaction term was p<0.0001, with an associated 65% increase
      in death, MI, or stroke (HR 1.65, 95% CI 1.00-2.73) in men and a 69% decrease (HR
      0.31, 95% CI 0.16-0.6) in women. CONCLUSIONS: Using two independent populations,
      this study is the first to document a significant interaction between CYP19A1
      genotype and sex on cardiovascular outcomes. These findings could illuminate
      potential mechanisms of sex differences in cardiovascular disease outcomes.

PMID- 21170324
TI  - Cancer risk in mothers of men operated for undescended testis.
AB  - BACKGROUND: Undescended testis, or cryptorchidism, occurs in 2-5% of boys born at
      term, and by 12 months of age about 1% of all boys have manifest cryptorchidism.
      Several hormonal substances control this process and disruption of the foetal sex
      hormones balance is a potential cause of undescended testis, however, to a great
      extent the aetiology of cryptorchidism is unclear. METHODOLOGY: To study risk
      factors involved in the aetiology of undescended testis, we assessed cancer risk
      in 15,885 mothers of men operated for undescended testis in Sweden. Women were
      followed-up for a median period of 23 years during which 811 first primary
      malignancies occurred. Their cancer incidence was compared with that in the
      general population estimating standardized incidence ratio (SIR) and
      corresponding 95% confidence interval (CI). PRINCIPAL FINDINGS: The overall
      cancer risk experienced by the mothers of cryptorchid men did not differ
      significantly from that of the general population (SIR = 0.94; 95% C.I. = 0.88
      1.01). Specifically, there was a reduction in ovarian cancer risk (SIR = 0.72;
      95% C.I. = 0.51-0.99), while the risk of lung (SIR = 1.38 95% C.I. 1.03-1.81) and
      biliary tract/liver cancer (SIR: 1.76, 95% CI: 1.03-2.82) were increased.
      CONCLUSIONS: Although we cannot rule out the role of chance, our data suggest a
      positive association between undescended testis and maternal lung cancer and a
      negative association with ovarian cancer, where the first may be partly
      attributable to smoking and the second to an altered hormonal milieu during
      pregnancy and thus both exposures may be risk factors for cryptorchidism.

PMID- 21170325
TI  - Kita driven expression of oncogenic HRAS leads to early onset and highly
      penetrant melanoma in zebrafish.
AB  - BACKGROUND: Melanoma is the most aggressive and lethal form of skin cancer.
      Because of the increasing incidence and high lethality of melanoma, animal models
      for continuously observing melanoma formation and progression as well as for
      testing pharmacological agents are needed. METHODOLOGY AND PRINCIPAL FINDINGS:
      Using the combinatorial Gal4-UAS system, we have developed a zebrafish transgenic
      line that expresses oncogenic HRAS under the kita promoter. Already at 3 days
      transgenic kita-GFP-RAS larvae show a hyper-pigmentation phenotype as earliest
      evidence of abnormal melanocyte growth. By 2-4 weeks, masses of transformed
      melanocytes form in the tail stalk of the majority of kita-GFP-RAS transgenic
      fish. The adult tumors evident between 1-3 months of age faithfully reproduce the
      immunological, histological and molecular phenotypes of human melanoma, but on a
      condensed time-line. Furthermore, they show transplantability, dependence on
      mitfa expression and do not require additional mutations in tumor suppressors. In
      contrast to kita expressing melanocyte progenitors that efficiently develop
      melanoma, mitfa expressing progenitors in a second Gal4-driver line were 4 times
      less efficient in developing melanoma during the three months observation period.
      CONCLUSIONS AND SIGNIFICANCE: This indicates that zebrafish kita promoter is a
      powerful tool for driving oncogene expression in the right cells and at the right
      level to induce early onset melanoma in the presence of tumor suppressors. Thus
      our zebrafish model provides a link between kita expressing melanocyte
      progenitors and melanoma and offers the advantage of a larval phenotype suitable
      for large scale drug and genetic modifier screens.

PMID- 21170326
TI  - FReD: the floral reflectance database--a web portal for analyses of flower
      colour.
AB  - BACKGROUND: Flower colour is of great importance in various fields relating to
      floral biology and pollinator behaviour. However, subjective human judgements of
      flower colour may be inaccurate and are irrelevant to the ecology and vision of
      the flower's pollinators. For precise, detailed information about the colours of
      flowers, a full reflectance spectrum for the flower of interest should be used
      rather than relying on such human assessments. METHODOLOGY/PRINCIPAL FINDINGS:
      The Floral Reflectance Database (FReD) has been developed to make an extensive
      collection of such data available to researchers. It is freely available at
      http://www.reflectance.co.uk. The database allows users to download spectral
      reflectance data for flower species collected from all over the world. These
      could, for example, be used in modelling interactions between pollinator vision
      and plant signals, or analyses of flower colours in various habitats. The
      database contains functions for calculating flower colour loci according to
      widely-used models of bee colour space, reflectance graphs of the spectra and an
      option to search for flowers with similar colours in bee colour space.
      CONCLUSIONS/SIGNIFICANCE: The Floral Reflectance Database is a valuable new tool
      for researchers interested in the colours of flowers and their association with
      pollinator colour vision, containing raw spectral reflectance data for a large
      number of flower species.

PMID- 21170327
TI  - Molecular evolution and functional divergence of the cytochrome P450 3 (CYP3)
      Family in Actinopterygii (ray-finned fish).
AB  - BACKGROUND: The cytochrome P450 (CYP) superfamily is a multifunctional
      hemethiolate enzyme that is widely distributed from Bacteria to Eukarya. The CYP3
      family contains mainly the four subfamilies CYP3A, CYP3B, CYP3C and CYP3D in
      vertebrates; however, only the Actinopterygii (ray-finned fish) have all four
      subfamilies and detailed understanding of the evolutionary relationship of
      Actinopterygii CYP3 family members would be valuable. METHODS AND FINDINGS:
      Phylogenetic relationships were constructed to trace the evolutionary history of
      the Actinopterygii CYP3 family genes. Selection analysis, relative rate tests and
      functional divergence analysis were combined to interpret the relationship of the
      site-specific evolution and functional divergence in the Actinopterygii CYP3
      family. The results showed that the four CYP3 subfamilies in Actinopterygii might
      be formed by gene duplication. The first gene duplication event was responsible
      for divergence of the CYP3B/C clusters from ancient CYP3 before the origin of the
      Actinopterygii, which corresponded to the fish-specific whole genome duplication
      (WGD). Tandem repeat duplication in each of the homologue clusters produced
      stable CYP3B, CYP3C, CYP3A and CYP3D subfamilies. Acceleration of asymmetric
      evolutionary rates and purifying selection together were the main force for the
      production of new subfamilies and functional divergence in the new subset after
      gene duplication, whereas positive selection was detected only in the retained
      CYP3A subfamily. Furthermore, nearly half of the functional divergence sites
      appear to be related to substrate recognition, which suggests that site-specific
      evolution is closely related with functional divergence in the Actinopterygii
      CYP3 family. CONCLUSIONS: The split of fish-specific CYP3 subfamilies was related
      to the fish-specific WGD, and site-specific acceleration of asymmetric
      evolutionary rates and purifying selection was the main force for the origin of
      the new subfamilies and functional divergence in the new subset after gene
      duplication. Site-specific evolution in substrate recognition was related to
      functional divergence in the Actinopterygii CYP3 family.

PMID- 21170328
TI  - Efficient utilization of rare variants for detection of disease-related genomic
      regions.
AB  - When testing association between rare variants and diseases, an efficient
      analytical approach involves considering a set of variants in a genomic region as
      the unit of analysis. One factor complicating this approach is that the vast
      majority of rare variants in practical applications are believed to represent
      background neutral variation. As a result, analyzing a single set with all
      variants may not represent a powerful approach. Here, we propose two alternative
      strategies. In the first, we analyze the subsets of rare variants exhaustively.
      In the second, we categorize variants selectively into two subsets: one in which
      variants are overrepresented in cases, and the other in which variants are
      overrepresented in controls. When the proportion of neutral variants is moderate
      to large we show, by simulations, that the both proposed strategies improve the
      statistical power over methods analyzing a single set with total variants. When
      applied to a real sequencing association study, the proposed methods consistently
      produce smaller p-values than their competitors. When applied to another real
      sequencing dataset to study the difference of rare allele distributions between
      ethnic populations, the proposed methods detect the overrepresentation of
      variants between the CHB (Chinese Han in Beijing) and YRI (Yoruba people of
      Ibadan) populations with small p-values. Additional analyses suggest that there
      is no difference between the CHB and CHD (Chinese Han in Denver) datasets, as
      expected. Finally, when applied to the CHB and JPT (Japanese people in Tokyo)
      populations, existing methods fail to detect any difference, while it is detected
      by the proposed methods in several regions.

PMID- 21170329
TI  - Acetaminophen induces apoptosis in rat cortical neurons.
AB  - BACKGROUND: Acetaminophen (AAP) is widely prescribed for treatment of mild pain
      and fever in western countries. It is generally considered a safe drug and the
      most frequently reported adverse effect associated with acetaminophen is
      hepatotoxicity, which generally occurs after acute overdose. During AAP overdose,
      encephalopathy might develop and contribute to morbidity and mortality. Our
      hypothesis is that AAP causes direct neuronal toxicity contributing to the
      general AAP toxicity syndrome. METHODOLOGY/PRINCIPAL FINDINGS: We report that AAP
      causes direct toxicity on rat cortical neurons both in vitro and in vivo as
      measured by LDH release. We have found that AAP causes concentration-dependent
      neuronal death in vitro at concentrations (1 and 2 mM) that are reached in human
      plasma during AAP overdose, and that are also reached in the cerebrospinal fluid
      of rats for 3 hours following i.p injection of AAP doses (250 and 500 mg/kg) that
      are below those required to induce acute hepatic failure in rats. AAP also
      increases both neuronal cytochrome P450 isoform CYP2E1 enzymatic activity and
      protein levels as determined by Western blot, leading to neuronal death through
      mitochondrial-mediated mechanisms that involve cytochrome c release and caspase 3
      activation. In addition, in vivo experiments show that i.p. AAP (250 and 500
      mg/kg) injection induces neuronal death in the rat cortex as measured by TUNEL,
      validating the in vitro data. CONCLUSIONS/SIGNIFICANCE: The data presented here
      establish, for the first time, a direct neurotoxic action by AAP both in vivo and
      in vitro in rats at doses below those required to produce hepatotoxicity and
      suggest that this neurotoxicity might be involved in the general toxic syndrome
      observed during patient APP overdose and, possibly, also when AAP doses in the
      upper dosing schedule are used, especially if other risk factors (moderate
      drinking, fasting, nutritional impairment) are present.

PMID- 21170330
TI  - Sublethal doses of anthrax lethal toxin on the suppression of macrophage
      phagocytosis.
AB  - BACKGROUND: Lethal toxin (LT), the major virulence factor produced by Bacillus
      anthracis, has been shown to suppress the immune system, which is beneficial to
      the establishment of B. anthracis infections. It has been suggested that the
      suppression of MEK/MAPK signaling pathways of leukocytes contributes to LT
      mediated immunosuppressive effects. However, the involvement of MAPK independent
      pathways has not been clearly elucidated; nor has the crucial role played by LT
      in the early stages of infection. Determining whether LT exerts any pathological
      effects before being enriched to an MEK inhibitory level is an important next
      step in the furtherance of this field. METHODOLOGY/PRINCIPAL FINDINGS: Using a
      cell culture model, we determined that low doses of LT inhibited phagocytosis of
      macrophages, without influencing MAPK pathways. Consistent low doses of LT
      significantly suppressed bacterial clearance and enhanced the mortality of mice
      with bacteremia, without suppressing the MEK1 of splenic and peripheral blood
      mononuclear cells. CONCLUSION/SIGNIFICANCE: These results suggest that LT
      suppresses the phagocytes in a dose range lower than that required to suppress
      MEK1 in the early stages of infection.

PMID- 21170331
TI  - Relationships linking amplification level to gene over-expression in gliomas.
AB  - BACKGROUND: Gene amplification is thought to promote over-expression of genes
      favouring tumour development. Because amplified regions are usually megabase
      long, amplification often concerns numerous syntenic or non-syntenic genes, among
      which only a subset is over-expressed. The rationale for these differences
      remains poorly understood. METHODOLOGY/PRINCIPAL FINDING: To address this
      question, we used quantitative RT-PCR to determine the expression level of a
      series of co-amplified genes in five xenografted and one fresh human gliomas.
      These gliomas were chosen because we have previously characterised in detail the
      genetic content of their amplicons. In all the cases, the amplified sequences lie
      on extra-chromosomal DNA molecules, as commonly observed in gliomas. We show here
      that genes transcribed in non-amplified gliomas are over-expressed when
      amplified, roughly in proportion to their copy number, while non-expressed genes
      remain inactive. When specific antibodies were available, we also compared
      protein expression in amplified and non-amplified tumours. We found that protein
      accumulation barely correlates with the level of mRNA expression in some of these
      tumours. CONCLUSIONS/SIGNIFICANCE: Here we show that the tissue-specific pattern
      of gene expression is maintained upon amplification in gliomas. Our study relies
      on a single type of tumour and a limited number of cases. However, it strongly
      suggests that, even when amplified, genes that are normally silent in a given
      cell type play no role in tumour progression. The loose relationships between
      mRNA level and protein accumulation and/or activity indicate that translational
      or post-translational events play a key role in fine-tuning the final outcome of
      amplification in gliomas.

PMID- 21170332
TI  - Mouse embryonic retina delivers information controlling cortical neurogenesis.
AB  - The relative contribution of extrinsic and intrinsic mechanisms to cortical
      development is an intensely debated issue and an outstanding question in
      neurobiology. Currently, the emerging view is that interplay between intrinsic
      genetic mechanisms and extrinsic information shape different stages of cortical
      development. Yet, whereas the intrinsic program of early neocortical
      developmental events has been at least in part decoded, the exact nature and
      impact of extrinsic signaling are still elusive and controversial. We found that
      in the mouse developing visual system, acute pharmacological inhibition of
      spontaneous retinal activity (retinal waves-RWs) during embryonic stages increase
      the rate of corticogenesis (cell cycle withdrawal). Furthermore, early
      perturbation of retinal spontaneous activity leads to changes of cortical layer
      structure at a later time point. These data suggest that mouse embryonic retina
      delivers long-distance information capable of modulating cell genesis in the
      developing visual cortex and that spontaneous activity is the candidate long
      distance acting extrinsic cue mediating this process. In addition, these data may
      support spontaneous activity to be a general signal coordinating neurogenesis in
      other developing sensory pathways or areas of the central nervous system.

PMID- 21170333
TI  - Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their
      transcriptome and their antiviral properties against hepatitis C virus.
AB  - BACKGROUND: Specific differences in signaling and antiviral properties between
      the different Lambda-interferons, a novel group of interferons composed of IL
      28A, IL-28B and IL-29, are currently unknown. This is the first study
      comparatively investigating the transcriptome and the antiviral properties of the
      Lambda-interferons IL-28A and IL-29. METHODOLOGY/PRINCIPAL FINDINGS: Expression
      studies were performed by microarray analysis, quantitative PCR (qPCR), reporter
      gene assays and immunoluminometric assays. Signaling was analyzed by Western
      blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV
      replicon. All hepatic cell lines investigated as well as primary hepatocytes
      expressed both IFN-lambda receptor subunits IL-10R2 and IFN-lambdaR1. Both, IL
      28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis,
      similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes;
      IL-29: 111 genes), many of them playing a role in antiviral immunity. However,
      only IL-28A was able to significantly down-regulate gene expression (n = 272 down
      regulated genes). Both cytokines significantly decreased HCV replication in Huh-7
      cells. In comparison to liver biopsies of patients with non-viral liver disease,
      liver biopsies of patients with HCV showed significantly increased mRNA
      expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were
      elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression
      was significantly increased. CONCLUSIONS/SIGNIFICANCE: IL-28A and IL-29 are up
      regulated in HCV patients and are similarly effective in inducing antiviral genes
      and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene
      repressor. Both IFN-lambdas may have therapeutic potential in the treatment of
      chronic HCV.

PMID- 21170334
TI  - Breakfast staple types affect brain gray matter volume and cognitive function in
      healthy children.
AB  - Childhood diet is important for brain development. Furthermore, the quality of
      breakfast is thought to affect the cognitive functioning of well-nourished
      children. To analyze the relationship among breakfast staple type, gray matter
      volume, and intelligence quotient (IQ) in 290 healthy children, we used magnetic
      resonance images and applied voxel-based morphometry. We divided subjects into
      rice, bread, and both groups according to their breakfast staple. We showed that
      the rice group had a significantly larger gray matter ratio (gray matter volume
      percentage divided by intracranial volume) and significantly larger regional gray
      matter volumes of several regions, including the left superior temporal gyrus.
      The bread group had significantly larger regional gray and white matter volumes
      of several regions, including the right frontoparietal region. The perceptual
      organization index (POI; IQ subcomponent) of the rice group was significantly
      higher than that of the bread group. All analyses were adjusted for age, gender,
      intracranial volume, socioeconomic status, average weekly frequency of having
      breakfast, and number of side dishes eaten for breakfast. Although several
      factors may have affected the results, one possible mechanism underlying the
      difference between the bread and the rice groups may be the difference in the
      glycemic index (GI) of these two substances; foods with a low GI are associated
      with less blood-glucose fluctuation than are those with a high GI. Our study
      suggests that breakfast staple type affects brain gray and white matter volumes
      and cognitive function in healthy children; therefore, a diet of optimal
      nutrition is important for brain maturation during childhood and adolescence.

PMID- 21170335
TI  - Analysis of ultra low genome conservation in Clostridium difficile.
AB  - Microarray-based comparative genome hybridisations (CGH) and genome sequencing of
      Clostridium difficile isolates have shown that the genomes of this species are
      highly variable. To further characterize their genome variation, we employed
      integration of data from CGH, genome sequencing and putative cellular pathways.
      Transcontinental strain comparison using CGH data confirmed the emergence of a
      human-specific hypervirulent cluster. However, there was no correlation between
      total toxin production and hypervirulent phenotype, indicating the possibility of
      involvement of additional factors towards hypervirulence. Calculation of C.
      difficile core and pan genome size using CGH and sequence data estimated that the
      core genome is composed of 947 to 1,033 genes and a pan genome comprised of 9,640
      genes. The reconstruction, annotation and analysis of cellular pathways revealed
      highly conserved pathways despite large genome variation. However, few pathways
      such as tetrahydrofolate biosynthesis were found to be variable and could be
      contributing to adaptation towards virulence such as antibiotic resistance.

PMID- 21170336
TI  - Molecular species identification with rich floristic sampling: DNA barcoding the
      pteridophyte flora of Japan.
AB  - BACKGROUND: DNA barcoding is expected to be an effective identification tool for
      organisms with heteromorphic generations such as pteridophytes, which possess a
      morphologically simple gametophyte generation. Although a reference data set
      including complete coverage of the target local flora/fauna is necessary for
      accurate identification, DNA barcode studies including such rich taxonomic
      sampling on a countrywide scale are lacking. METHODOLOGY/PRINCIPAL FINDINGS: The
      Japanese pteridophyte flora (733 taxa including subspecies and varieties) was
      used to test the utility of two plastid DNA barcode regions (rbcL and trnH-psbA)
      with the intention of developing an identification system for native
      gametophytes. DNA sequences were obtained from each of 689 (94.0%) taxa for rbcL
      and 617 (84.2%) taxa for trnH-psbA. Mean interspecific divergence values across
      all taxon pairs (K2P genetic distances) did not reveal a significant difference
      in rate between trnH-psbA and rbcL, but mean K2P distances of each genus showed
      significant heterogeneity according to systematic position. The minimum fail rate
      of taxon discrimination in an identification test using BLAST (12.52%) was
      obtained when rbcL and trnH-psbA were combined, and became lower in datasets
      excluding infraspecific taxa or apogamous taxa, or including sexual diploids
      only. CONCLUSIONS/SIGNIFICANCE: This study demonstrates the overall effectiveness
      of DNA barcodes for species identification in the Japanese pteridophyte flora.
      Although this flora is characterized by a high occurrence of apogamous taxa that
      pose a serious challenge to identification using DNA barcodes, such taxa are
      limited to a small number of genera, and only minimally detract from the overall
      success rate. In the case that a query sequence is matched to a known apogamous
      genus, routine species identification may not be possible. Otherwise, DNA
      barcoding is a practical tool for identification of most Japanese pteridophytes,
      and is especially anticipated to be helpful for identification of non-hybridizing
      gametophytes.

PMID- 21170337
TI  - Oligomeric coiled-coil adhesin YadA is a double-edged sword.
AB  - Yersinia adhesin A (YadA) is an essential virulence factor for the food-borne
      pathogens Yersinia enterocolitica and Yersinia pseudotuberculosis. Surprisingly,
      it is a pseudogene in Yersinia pestis. Even more intriguing, the introduction of
      a functional yadA gene in Y. pestis EV76 was shown to correlate with a decrease
      in virulence in a mouse model. Here, we report that wild type (wt) Y.
      enterocolitica E40, as well as YadA-deprived E40 induced the synthesis of
      neutrophil extracellular traps (NETs) upon contact with neutrophils, but only
      YadA-expressing Y. enterocolitica adhered to NETs and were killed. As binding
      seemed to be a prerequisite for killing, we searched for YadA-binding substrates
      and detected the presence of collagen within NETs. E40 bacteria expressing
      V98D,N99A mutant YadA with a severely reduced ability to bind collagen were found
      to be more resistant to killing, suggesting that collagen binding contributes
      significantly to sensitivity to NETs. Wt Y. pestis EV76 were resistant to killing
      by NETs, while recombinant EV76 expressing YadA from either Y. pseudotuberculosis
      or Y. enterocolitica were sensitive to killing by NETs, outlining the importance
      of YadA for susceptibility to NET-dependent killing. Recombinant EV76 endowed
      with YadA from Y. enterocolitica were also less virulent for the mouse than wt
      EV76, as shown before. In addition, EV76 carrying wt YadA were less virulent for
      the mouse than EV76 expressing YadA(V98D,N99A). The observation that YadA makes
      Yersinia sensitive to NETs provides an explanation as for why evolution selected
      for the inactivation of yadA in the flea-borne Y. pestis and clarifies an old
      enigma. Since YadA imposes the same cost to the food-borne Yersinia but was
      nevertheless conserved by evolution, this observation also illustrates the
      duality of some virulence functions.

PMID- 21170338
TI  - ZNF274 recruits the histone methyltransferase SETDB1 to the 3' ends of ZNF genes.
AB  - Only a small percentage of human transcription factors (e.g. those associated
      with a specific differentiation program) are expressed in a given cell type.
      Thus, cell fate is mainly determined by cell type-specific silencing of
      transcription factors that drive different cellular lineages. Several histone
      modifications have been associated with gene silencing, including H3K27me3 and
      H3K9me3. We have previously shown that genes for the two largest classes of
      mammalian transcription factors are marked by distinct histone modifications;
      homeobox genes are marked by H3K27me3 and zinc finger genes are marked by
      H3K9me3. Several histone methyltransferases (e.g. G9a and SETDB1) may be involved
      in mediating the H3K9me3 silencing mark. We have used ChIP-chip and ChIP-seq to
      demonstrate that SETDB1, but not G9a, is associated with regions of the genome
      enriched for H3K9me3. One current model is that SETDB1 is recruited to specific
      genomic locations via interaction with the corepressor TRIM28 (KAP1), which is in
      turn recruited to the genome via interaction with zinc finger transcription
      factors that contain a Kruppel-associated box (KRAB) domain. However, specific
      KRAB-ZNFs that recruit TRIM28 (KAP1) and SETDB1 to the genome have not been
      identified. We now show that ZNF274 (a KRAB-ZNF that contains 5 C2H2 zinc finger
      domains), can interact with KAP1 both in vivo and in vitro and, using ChIP-seq,
      we show that ZNF274 binding sites co-localize with SETDB1, KAP1, and H3K9me3 at
      the 3' ends of zinc finger genes. Knockdown of ZNF274 with siRNAs reduced the
      levels of KAP1 and SETDB1 recruitment to the binding sites. These studies provide
      the first identification of a KRAB domain-containing ZNF that is involved in
      recruitment of the KAP1 and SETDB1 to specific regions of the human genome.

PMID- 21170339
TI  - Acute stress induces contrasting changes in AMPA receptor subunit phosphorylation
      within the prefrontal cortex, amygdala and hippocampus.
AB  - Exposure to stress causes differential neural modifications in various limbic
      regions, namely the prefrontal cortex, hippocampus and amygdala. We investigated
      whether alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)
      phosphorylation is involved with these stress effects. Using an acute inescapable
      stress protocol with rats, we found opposite effects on AMPA receptor
      phosphorylation in the medial prefrontal cortex (mPFC) and dorsal hippocampus
      (DH) compared to the amygdala and ventral hippocampus (VH). After stress, the
      phosphorylation of Ser831-GluA1 was markedly decreased in the mPFC and DH,
      whereas the phosphorylation of Ser845-GluA1 was increased in the amygdala and VH.
      Stress also modulated the GluA2 subunit with a decrease in the phosphorylation of
      both Tyr876-GluA2 and Ser880-GluA2 residues in the amygdala, and an increase in
      the phosphorylation of Ser880-GluA2 in the mPFC. These results demonstrate that
      exposure to acute stress causes subunit-specific and region-specific changes in
      glutamatergic transmission, which likely lead to the reduced synaptic efficacy in
      the mPFC and DH and augmented activity in the amygdala and VH. In addition, these
      findings suggest that modifications of glutamate receptor phosphorylation could
      mediate the disruptive effects of stress on cognition. They also provide a means
      to reconcile the contrasting effects that stress has on synaptic plasticity in
      these regions. Taken together, the results provide support for a brain region
      oriented approach to therapeutics.

PMID- 21170340
TI  - Direct injection of functional single-domain antibodies from E. coli into human
      cells.
AB  - Intracellular proteins have a great potential as targets for therapeutic
      antibodies (Abs) but the plasma membrane prevents access to these antigens. Ab
      fragments and IgGs are selected and engineered in E. coli and this microorganism
      may be also an ideal vector for their intracellular delivery. In this work we
      demonstrate that single-domain Ab (sdAbs) can be engineered to be injected into
      human cells by E. coli bacteria carrying molecular syringes assembled by a type
      III protein secretion system (T3SS). The injected sdAbs accumulate in the
      cytoplasm of HeLa cells at levels ca. 105-106 molecules per cell and their
      functionality is shown by the isolation of sdAb-antigen complexes. Injection of
      sdAbs does not require bacterial invasion or the transfer of genetic material.
      These results are proof-of-principle for the capacity of E. coli bacteria to
      directly deliver intracellular sdAbs (intrabodies) into human cells for
      analytical and therapeutic purposes.

PMID- 21170341
TI  - "I'm worth more than that": trait positivity predicts increased rejection of
      unfair financial offers.
AB  - Humans react strongly to unfairness, sometimes rejecting inequitable proposals
      even if this sacrifices personal financial gain. Here we explored whether
      emotional dispositions--trait tendencies to experience positive or negative
      feelings--shape the rejection of unfair financial offers. Participants played an
      Ultimatum Game, where the division of a sum of money is proposed and the player
      can accept or reject this offer. Individuals high in trait positivity and low in
      trait negativity rejected more unfair offers. These relationships could not be
      explained by existing accounts which argue that rejection behaviour results from
      a failure to regulate negative emotions, or serves to arbitrate social
      relationships and identity. Instead, the relationship between dispositional
      affect and rejection behaviour may be underpinned by perceived self worth, with
      those of a positive disposition believing that they are "worth more than that"
      and those of a negative disposition resigning themselves to "taking the crumbs
      from under the table".

PMID- 21170342
TI  - Mutational escape in HIV-1 CTL epitopes leads to increased binding to inhibitory
      myelomonocytic MHC class I receptors.
AB  - Escape mutations in HIV-1 cytotoxic T cell (CTL) epitopes can abrogate
      recognition by the TCR of HIV-1-specific CD8+ T cells, but may also change
      interactions with alternative MHC class I receptors. Here, we show that
      mutational escape in three HLA-A11-, B8- and B7- restricted immunodominant HIV-1
      CTL epitopes consistently enhances binding of the respective peptide/MHC class I
      complex to Immunoglobulin-like transcript 4 (ILT4), an inhibitory myelomonocytic
      MHC class I receptor expressed on monocytes and dendritic cells. In contrast,
      mutational escape in an alternative immunodominant HLA-B57-restricted CTL epitope
      did not affect ILT4-mediated recognition by myelomonocytic cells. This suggests
      that in addition to abrogating recognition by HIV-1-specific CD8 T cells,
      mutational escape in some, but not all CTL epitopes may mediate important
      immunoregulatory effects by increasing binding properties to ILT4, and augmenting
      ILT4-mediated inhibitory effects of professional antigen-presenting cells.

PMID- 21170343
TI  - Visualization of allostery in P-selectin lectin domain using MD simulations.
AB  - Allostery of P-selectin lectin (Lec) domain followed by an epithelial growth
      factor (EGF)-like domain is essential for its biological functionality, but the
      underlying pathways have not been well understood. Here the molecular dynamics
      simulations were performed on the crystallized structures to visualize the
      dynamic conformational change for state 1 (S1) or state 2 (S2) Lec domain with
      respective bent (B) or extended (E) EGF orientation. Simulations illustrated that
      both S1 and S2 conformations were unable to switch from one to another directly.
      Instead, a novel S1' conformation was observed from S1 when crystallized B-S1 or
      reconstructed "E-S1" structure was employed, which was superposed well with that
      of equilibrated S1 Lec domain alone. It was also indicated that the corresponding
      allosteric pathway from S1 to S1' conformation started with the separation
      between residues Q30 and K67 and terminated with the release of residue N87 from
      residue C109. These results provided an insight into understanding the structural
      transition and the structure-function relationship of P-selectin allostery.

PMID- 21170344
TI  - Hyperacute directional hearing and phonotactic steering in the cricket (Gryllus
      bimaculatus deGeer).
AB  - BACKGROUND: Auditory mate or prey localisation is central to the lifestyle of
      many animals and requires precise directional hearing. However, when the incident
      angle of sound approaches 0 degrees  azimuth, interaural time and intensity
      differences gradually vanish. This poses a demanding challenge to animals
      especially when interaural distances are small. To cope with these limitations
      imposed by the laws of acoustics, crickets employ a frequency tuned peripheral
      hearing system. Although this enhances auditory directionality the actual
      precision of directional hearing and phonotactic steering has never been studied
      in the behaviourally important frontal range. PRINCIPAL FINDINGS: Here we
      analysed the directionality of phonotaxis in female crickets (Gryllus
      bimaculatus) walking on an open-loop trackball system by measuring their steering
      accuracy towards male calling song presented at frontal angles of incidence.
      Within the range of +/-30 degrees , females reliably discriminated the side of
      acoustic stimulation, even when the sound source deviated by only 1 degrees  from
      the animal's length axis. Moreover, for angles of sound incidence between 1
      degrees  and 6 degrees  the females precisely walked towards the sound source.
      Measuring the tympanic membrane oscillations of the front leg ears with a laser
      vibrometer revealed between 0 degrees  and 30 degrees  a linear increasing
      function of interaural amplitude differences with a slope of 0.4 dB/ degrees .
      Auditory nerve recordings closely reflected these bilateral differences in
      afferent response latency and intensity that provide the physiological basis for
      precise auditory steering. CONCLUSIONS: Our experiments demonstrate that an
      insect hearing system based on a frequency-tuned pressure difference receiver
      achieves directional hyperacuity which easily rivals best directional hearing in
      mammals and birds. Moreover, this directional accuracy of the cricket's hearing
      system is reflected in the animal's phonotactic motor response.

PMID- 21170345
TI  - Design, validation and annotation of transcriptome-wide oligonucleotide probes
      for the oligochaete annelid Eisenia fetida.
AB  - High density oligonucleotide probe arrays have increasingly become an important
      tool in genomics studies. In organisms with incomplete genome sequence, one
      strategy for oligo probe design is to reduce the number of unique probes that
      target every non-redundant transcript through bioinformatic analysis and
      experimental testing. Here we adopted this strategy in making oligo probes for
      the earthworm Eisenia fetida, a species for which we have sequenced transcriptome
      scale expressed sequence tags (ESTs). Our objectives were to identify unique
      transcripts as targets, to select an optimal and non-redundant oligo probe for
      each of these target ESTs, and to annotate the selected target sequences. We
      developed a streamlined and easy-to-follow approach to the design, validation and
      annotation of species-specific array probes. Four 244K-formatted oligo arrays
      were designed using eArray and were hybridized to a pooled E. fetida cRNA sample.
      We identified 63,541 probes with unsaturated signal intensities consistently
      above the background level. Target transcripts of these probes were annotated
      using several sequence alignment algorithms. Significant hits were obtained for
      37,439 (59%) probed targets. We validated and made publicly available 63.5K oligo
      probes so the earthworm research community can use them to pursue ecological,
      toxicological, and other functional genomics questions. Our approach is
      efficient, cost-effective and robust because it (1) does not require a major
      genomics core facility; (2) allows new probes to be easily added and old probes
      modified or eliminated when new sequence information becomes available, (3) is
      not bioinformatics-intensive upfront but does provide opportunities for more in
      depth annotation of biological functions for target genes; and (4) if desired,
      EST orthologs to the UniGene clusters of a reference genome can be identified and
      selected in order to improve the target gene specificity of designed probes. This
      approach is particularly applicable to organisms with a wealth of EST sequences
      but unfinished genome.

PMID- 21170346
TI  - Patterns of recombination activity on mouse chromosome 11 revealed by high
      resolution mapping.
AB  - The success of high resolution genetic mapping of disease predisposition and
      quantitative trait loci in humans and experimental animals depends on the
      positions of key crossover events around the gene of interest. In mammals, the
      majority of recombination occurs at highly delimited 1-2 kb long sites known as
      recombination hotspots, whose locations and activities are distributed unevenly
      along the chromosomes and are tightly regulated in a sex specific manner. The
      factors determining the location of hotspots started to emerge with the finding
      of PRDM9 as a major hotspot regulator in mammals, however, additional factors
      modulating hotspot activity and sex specificity are yet to be defined. To address
      this limitation, we have collected and mapped the locations of 4829 crossover
      events occurring on mouse chromosome 11 in 5858 meioses of male and female
      reciprocal F1 hybrids of C57BL/6J and CAST/EiJ mice. This chromosome was chosen
      for its medium size and high gene density and provided a comparison with our
      previous analysis of recombination on the longest mouse chromosome 1. Crossovers
      were mapped to an average resolution of 127 kb, and thirteen hotspots were mapped
      to <8 kb. Most crossovers occurred in a small number of the most active hotspots.
      Females had higher recombination rate than males as a consequence of differences
      in crossover interference and regional variation of sex specific rates along the
      chromosome. Comparison with chromosome 1 showed that recombination events tend to
      be positioned in similar fashion along the centromere-telomere axis but
      independently of the local gene density. It appears that mammalian recombination
      is regulated on at least three levels, chromosome-wide, regional, and at
      individual hotspots, and these regulation levels are influenced by sex and
      genetic background but not by gene content.

PMID- 21170347
TI  - Rab27a is required for human cytomegalovirus assembly.
AB  - Human cytomegalovirus (HCMV) completes its final envelopment on intracellular
      membranes before it is released from the cell. The mechanisms underlying these
      processes are not understood. Here we studied the role of Rab27a, a regulator of
      lysosome-related organelle transport, in HCMV production. HCMV infection
      increased Rab27a expression, and recruitment of Rab27a to membranous strutures at
      the assembly site. Immuno-gold labelling demonstrated association of Rab27a with
      viral envelopes. CMV production was reduced after knock-down of Rab27a, and in
      Rab27a-deficient ashen melanocytes. This study shows a requirement for Rab27a in
      the CMV life cycle and suggests that CMV and LRO biogenesis share common
      molecular mechanisms.

PMID- 21170348
TI  - Changes in ponderal index and body mass index across childhood and their
      associations with fat mass and cardiovascular risk factors at age 15.
AB  - BACKGROUND: Little is known about whether associations between childhood
      adiposity and later adverse cardiovascular health outcomes are driven by tracking
      of overweight from childhood to adulthood and/or by vascular and metabolic
      changes from childhood overweight that persist into adulthood. Our objective is
      to characterise associations between trajectories of adiposity across childhood
      and a wide range of cardiovascular risk factors measured in adolescence, and
      explore the extent to which these are mediated by fat mass at age 15. METHODS AND
      FINDINGS: Using data from the Avon Longitudinal Study of Parents and Children, we
      estimated individual trajectories of ponderal index (PI) from 0-2 years and BMI
      from 2-10 years using random-effects linear spline models (N = 4601). We explored
      associations between PI/BMI trajectories and DXA-determined total-body fat-mass
      and cardiovascular risk factors at 15 years (systolic and diastolic blood
      pressure, fasting LDL- and HDL-cholesterol, triglycerides, C-reactive protein,
      glucose, insulin) with and without adjustment for confounders. Changes in PI/BMI
      during all periods of infancy and childhood were associated with greater DXA
      determined fat-mass at age 15. BMI changes in childhood, but not PI changes from
      0-2 years, were associated with most cardiovascular risk factors in adolescence;
      associations tended to be strongest for BMI changes in later childhood (ages 8.5
      10), and were largely mediated by fat mass at age 15. CONCLUSION: Changes in
      PI/BMI from 0-10 years were associated with greater fat-mass at age 15. Greater
      increases in BMI from age 8.5-10 years are most strongly associated with
      cardiovascular risk factors at age 15, with much of these associations mediated
      by fat-mass at this age. We found little evidence supporting previous reports
      that rapid PI changes in infancy are associated with future cardiovascular risk.
      This study suggests that associations between early overweight and subsequent
      adverse cardiovascular health are largely due to overweight children tending to
      remain overweight.

PMID- 21170349
TI  - Tracing the origin of the fungal alpha1 domain places its ancestor in the HMG-box
      superfamily: implication for fungal mating-type evolution.
AB  - BACKGROUND: Fungal mating types in self-incompatible Pezizomycotina are specified
      by one of two alternate sequences occupying the same locus on corresponding
      chromosomes. One sequence is characterized by a gene encoding an HMG protein,
      while the hallmark of the other is a gene encoding a protein with an alpha1
      domain showing similarity to the Matalpha1p protein of Saccharomyces cerevisiae.
      DNA-binding HMG proteins are ubiquitous and well characterized. In contrast,
      alpha1 domain proteins have limited distribution and their evolutionary origin is
      obscure, precluding a complete understanding of mating-type evolution in
      Ascomycota. Although much work has focused on the role of the S. cerevisiae
      Matalpha1p protein as a transcription factor, it has not yet been placed in any
      of the large families of sequence-specific DNA-binding proteins.
      METHODOLOGY/PRINCIPAL FINDINGS: We present sequence comparisons, phylogenetic
      analyses, and in silico predictions of secondary and tertiary structures, which
      support our hypothesis that the alpha1 domain is related to the HMG domain. We
      have also characterized a new conserved motif in alpha1 proteins of
      Pezizomycotina. This motif is immediately adjacent to and downstream of the
      alpha1 domain and consists of a core sequence Y-[LMIF]-x(3)-G-[WL] embedded in a
      larger conserved motif. CONCLUSIONS/SIGNIFICANCE: Our data suggest that extant
      alpha1-box genes originated from an ancestral HMG gene, which confirms the
      current model of mating-type evolution within the fungal kingdom. We propose to
      incorporate alpha1 proteins in a new subclass of HMG proteins termed
      MATalpha_HMG.

PMID- 21170351
TI  - Galactosylated poly(ethylene glycol)-b-poly (l-lactide-co-beta-malic acid) block
      copolymer micelles for targeted drug delivery: preparation and in vitro
      characterization.
AB  - Biodegradable galactosylated methoxy poly(ethylene glycol)/poly(l-lactide-co-beta
      malic acid) (Gal-PEG-b-PLMA) block copolymer micelles were successfully prepared
      by a solvent diffusion method, and could efficiently encapsulate doxorubicin. The
      Gal-PEG-b-PLMA micelles before and after doxorubicin loading were characterized
      by size, morphology, in vitro drug release, and in vitro cytotoxicity in HepG2
      cells. Transmission electron microscopy and dynamic light scattering results
      showed that the empty and doxorubicin-loaded micelles were approximately
      spherical in shape and had mean sizes of about 72 nm and 85 nm, respectively. In
      vitro release behavior of doxorubicin from the micelles was pH-dependent, with
      obviously faster release rates at mildly acidic pH 4.5 and 5.5 compared with
      physiologic pH 7.4. Methylthiazoletetrazolium assay and flow cytometric analysis
      indicated that the doxorubicin-loaded galactosylated micelles exhibited a greater
      growth-inhibitory effect on HepG2 cells than the nongalactosylated doxorubicin
      loaded micelles, and induced S phase cell cycle arrest. Confocal laser scanning
      microscope observations revealed that the galactosylated micelles could be
      efficiently internalized by HepG2 cells through receptor-mediated endocytosis.
      The results suggest that Gal-PEG-b-PLMA copolymer micelles are a promising
      carrier system for targeted drug delivery in cancer therapy.

PMID- 21170350
TI  - Unlocking biomarker discovery: large scale application of aptamer proteomic
      technology for early detection of lung cancer.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer deaths worldwide. New
      diagnostics are needed to detect early stage lung cancer because it may be cured
      with surgery. However, most cases are diagnosed too late for curative surgery.
      Here we present a comprehensive clinical biomarker study of lung cancer and the
      first large-scale clinical application of a new aptamer-based proteomic
      technology to discover blood protein biomarkers in disease. METHODOLOGY/PRINCIPAL
      FINDINGS: We conducted a multi-center case-control study in archived serum
      samples from 1,326 subjects from four independent studies of non-small cell lung
      cancer (NSCLC) in long-term tobacco-exposed populations. Sera were collected and
      processed under uniform protocols. Case sera were collected from 291 patients
      within 8 weeks of the first biopsy-proven lung cancer and prior to tumor removal
      by surgery. Control sera were collected from 1,035 asymptomatic study
      participants with >= 10 pack-years of cigarette smoking. We measured 813 proteins
      in each sample with a new aptamer-based proteomic technology, identified 44
      candidate biomarkers, and developed a 12-protein panel (cadherin-1, CD30 ligand,
      endostatin, HSP90alpha, LRIG3, MIP-4, pleiotrophin, PRKCI, RGM-C, SCF-sR, sL
      selectin, and YES) that discriminates NSCLC from controls with 91% sensitivity
      and 84% specificity in cross-validated training and 89% sensitivity and 83%
      specificity in a separate verification set, with similar performance for early
      and late stage NSCLC. CONCLUSIONS/SIGNIFICANCE: This study is a significant
      advance in clinical proteomics in an area of high unmet clinical need. Our
      analysis exceeds the breadth and dynamic range of proteome interrogated of
      previously published clinical studies of broad serum proteome profiling platforms
      including mass spectrometry, antibody arrays, and autoantibody arrays. The
      sensitivity and specificity of our 12-biomarker panel improves upon published
      protein and gene expression panels. Separate verification of classifier
      performance provides evidence against over-fitting and is encouraging for the
      next development phase, independent validation. This careful study provides a
      solid foundation to develop tests sorely needed to identify early stage lung
      cancer.

PMID- 21170352
TI  - Endostar-loaded PEG-PLGA nanoparticles: in vitro and in vivo evaluation.
AB  - Endostar, a novel recombinant human endostatin, which was approved by the Chinese
      State Food and Drug Administration in 2005, has a broad spectrum of activity
      against solid tumors. In this study, we aimed to determine whether the anticancer
      effect of Endostar is increased by using a nanocarrier system. It is expected
      that the prolonged circulation of endostar will improve its anticancer activity.
      Endostar-loaded nanoparticles were prepared to improve controlled release of the
      drug in mice and rabbits, as well as its anticancer effects in mice with colon
      cancer. A protein release system could be exploited to act as a drug carrier.
      Nanoparticles were formulated from poly (ethylene glycol) modified poly (DL
      lactide-co-glycolide) (PEG-PLGA) by a double emulsion technique. Physical and
      release characteristics of endostar-loaded nanoparticles in vitro were evaluated
      by transmission electron microscopy (TEM), photon correlation spectroscopy (PCS),
      and micro bicinchoninic acid protein assay. The pharmacokinetic parameters of
      endostar nanoparticles in rabbit and mice plasma were measured by enzyme-linked
      immunosorbent assay. Western blot was used to detect endostatin in different
      tissues. To study the effects of endostar-loaded nanoparticles in vivo, nude mice
      in which tumor cells HT-29 were implanted, were subsequently treated with
      endostar or endostar-loaded PEG-PLGA nanoparticles. Using TEM and PCS, endostar
      loaded PEG-PLGA nanoparticles were found to have a spherical core-shell structure
      with a diameter of 169.56 +/- 35.03 nm. Drug-loading capacity was 8.22% +/- 2.35%
      and drug encapsulation was 80.17% +/- 7.83%. Compared with endostar, endostar
      loaded PEG-PLGA nanoparticles had a longer elimination half-life and lower peak
      concentration, caused slower growth of tumor cell xenografts, and prolonged tumor
      doubling times. The nanoparticles changed the pharmacokinetic characteristics of
      endostar in mice and rabbits, thereby reinforcing anticancer activity. In
      conclusion, PEG-PLGA nanoparticles are a feasible carrier for endostar. Endostar
      loaded PEG-PLGA nanoparticles seem to have a better anticancer effect than
      conventional endostar. We believe that PEG-PLGA nanoparticles are an effective
      carrier for protein medicines.

PMID- 21170353
TI  - Recent advances in PEG-PLA block copolymer nanoparticles.
AB  - Due to their small particle size and large and modifiable surface, nanoparticles
      have unique advantages compared with other drug carriers. As a research focus in
      recent years, polyethylene glycol-polylactic acid (PEG-PLA) block copolymer and
      its end-group derivative nanoparticles can enhance the drug loading of
      hydrophobic drugs, reduce the burst effect, avoid being engulfed by phagocytes,
      increase the circulation time of drugs in blood, and improve bioavailability.
      Additionally, due to their smaller particle size and modified surface, these
      nanoparticles can accumulate in inflammation or target locations to enhance drug
      efficacy and reduce toxicity. Recent advances in PEG-PLA block copolymer
      nanoparticles, including the synthesis of PEG-PLA and the preparation of PEG-PLA
      nanoparticles, were introduced in this study, in particular the drug release and
      modifiable characteristics of PEG-PLA nanoparticles and their application in
      pharmaceutical preparations.

PMID- 21170354
TI  - Synthesis of silver/montmorillonite nanocomposites using gamma-irradiation.
AB  - Silver nanoparticles (Ag-NPs) were synthesized into the interlamellar space of
      montmorillonite (MMT) by using the gamma-irradiation technique in the absence of
      any reducing agent or heat treatment. Silver nitrate and gamma-irradiation were
      used as the silver precursor and physical reducing agent in MMT as a solid
      support. The MMT was suspended in the aqueous AgNO(3) solution, and after the
      absorption of silver ions, Ag(+) was reduced using the gamma-irradiation
      technique. The properties of Ag/MMT nanocomposites and the diameters of Ag-NPs
      were studied as a function of gamma-irradiation doses. The interlamellar space
      limited particle growth (d-spacing [d(s)] = 1.24-1.42 nm); powder X-ray
      diffraction and transmission electron microscopy (TEM) measurements showed the
      production of face-centered cubic Ag-NPs with a mean diameter of about 21.57
      30.63 nm. Scanning electron microscopy images indicated that there were structure
      changes between the initial MMT and Ag/MMT nanocomposites under the increased
      doses of gamma-irradiation. Furthermore, energy dispersive X-ray fluorescence
      spectra for the MMT and Ag/ MMT nanocomposites confirmed the presence of
      elemental compounds in MMT and Ag-NPs. The results from ultraviolet-visible
      spectroscopy and TEM demonstrated that increasing the gamma-irradiation dose
      enhanced the concentration of Ag-NPs. In addition, the particle size of the Ag
      NPs gradually increased from 1 to 20 kGy. When the gamma-irradiation dose
      increased from 20 to 40 kGy, the particle diameters decreased suddenly as a
      result of the induced fragmentation of Ag-NPs. Thus, Fourier transform infrared
      spectroscopy suggested that the interactions between Ag-NPs with the surface of
      MMT were weak due to the presence of van der Waals interactions. The synthesized
      Ag/MMT suspension was found to be stable over a long period of time (ie, more
      than 3 months) without any sign of precipitation.

PMID- 21170355
TI  - Biocompatibility of Fe3O4/DNR magnetic nanoparticles in the treatment of
      hematologic malignancies.
AB  - PURPOSE: The objectives of this research were to assess the biocompatibility of
      self-assembled Fe(3)O(4) magnetic nanoparticles (MNPs) loaded with daunorubicin
      (DNR), ie, (Fe(3)O(4)-MNPs/DNR), and to explore their potential application in
      the treatment of hematologic malignancies. METHODS: A hemolysis test was carried
      out to estimate the hematologic toxicity of Fe(3)O(4)- MNPs/DNR and a
      micronucleus assay was undertaken to identify its genotoxicity. Fe(3)O(4)-MNPs/
      DNR were injected intraperitoneally into mice to calculate the median lethal dose
      (LD(50)). The general condition of the mice was recorded, along with testing for
      acute toxicity to the liver and kidneys. RESULTS: Hemolysis rates were 2.908%,
      2.530%, and 2.415% after treatment with different concentrations of Fe(3)O(4)
      MNPs/DNR. In the micronucleus assay, there was no significant difference in
      micronucleus formation rate between the experimental Fe(3)O(4)-MNPs/DNR groups
      and negative controls (P > 0.05), but there was a significant difference between
      the experimental groups and the positive controls (P < 0.05). The LD(50) of the
      Fe(3)O(4)-MNPs/DNR was 1009.71 mg/kg and the 95% confidence interval (CI) was
      769.11-1262.40 mg/kg, while that of the DNR groups was 8.51 mg/kg (95% CI: 6.48
      10.37 mg/kg), suggesting that these nanoparticles have a wide safety margin.
      Acute toxicity testing showed no significant difference in body weight between
      the treatment groups at 24, 48, and 72 hours after intraperitoneal injection. The
      mice were all in good condition, with normal consumption of water and food, and
      their stools were formed and yellowish-brown. Interestingly, no toxic reactions,
      including instability of gait, convulsion, paralysis, and respiratory depression,
      were observed. Furthermore, alanine transaminase, blood urea nitrogen, and
      creatinine clearance in the experimental Fe(3)O(4)-MNPs/ DNR groups were 66.0 +/-
      28.55 U/L, 9.06 +/- 1.05 mmol/L, and 18.03 +/- 1.84 MUmol/L, respectively, which
      was not significantly different compared with the control and isodose DNR groups.
      CONCLUSION: Self-assembled Fe(3)O(4)-MNPs/DNR appear to be highly biocompatible
      and safe nanoparticles, and may be suitable for further application in the
      treatment of hematologic malignancies.

PMID- 21170357
TI  - Histone H2A C-terminus regulates chromatin dynamics, remodeling, and histone H1
      binding.
AB  - The tails of histone proteins are central players for all chromatin-mediated
      processes. Whereas the N-terminal histone tails have been studied extensively,
      little is known about the function of the H2A C-terminus. Here, we show that the
      H2A C-terminal tail plays a pivotal role in regulating chromatin structure and
      dynamics. We find that cells expressing C-terminally truncated H2A show increased
      stress sensitivity. Moreover, both the complete and the partial deletion of the
      tail result in increased histone exchange kinetics and nucleosome mobility in
      vivo and in vitro. Importantly, our experiments reveal that the H2A C-terminus is
      required for efficient nucleosome translocation by ISWI-type chromatin remodelers
      and acts as a novel recognition module for linker histone H1. Thus, we suggest
      that the H2A C-terminal tail has a bipartite function: stabilisation of the
      nucleosomal core particle, as well as mediation of the protein interactions that
      control chromatin dynamics and conformation.

PMID- 21170356
TI  - Cholera- and anthrax-like toxins are among several new ADP-ribosyltransferases.
AB  - Chelt, a cholera-like toxin from Vibrio cholerae, and Certhrax, an anthrax-like
      toxin from Bacillus cereus, are among six new bacterial protein toxins we
      identified and characterized using in silico and cell-based techniques. We also
      uncovered medically relevant toxins from Mycobacterium avium and Enterococcus
      faecalis. We found agriculturally relevant toxins in Photorhabdus luminescens and
      Vibrio splendidus. These toxins belong to the ADP-ribosyltransferase family that
      has conserved structure despite low sequence identity. Therefore, our search for
      new toxins combined fold recognition with rules for filtering sequences-
      including a primary sequence pattern--to reduce reliance on sequence identity and
      identify toxins using structure. We used computers to build models and analyzed
      each new toxin to understand features including: structure, secretion, cell
      entry, activation, NAD+ substrate binding, intracellular target binding and the
      reaction mechanism. We confirmed activity using a yeast growth test. In this era
      where an expanding protein structure library complements abundant protein
      sequence data--and we need high-throughput validation--our approach provides
      insight into the newest toxin ADP-ribosyltransferases.

PMID- 21170358
TI  - Endocytic sorting and recycling require membrane phosphatidylserine asymmetry
      maintained by TAT-1/CHAT-1.
AB  - Endocytic sorting is achieved through the formation of morphologically and
      functionally distinct sub-domains within early endosomes. Cargoes destined for
      recycling are sorted to and transported through newly-formed tubular membranes,
      but the processes that regulate membrane tubulation are poorly understood. Here,
      we identified a novel Caenorhabditis elegans Cdc50 family protein, CHAT-1, which
      acts as the chaperone of the TAT-1 P4-ATPase to regulate membrane
      phosphatidylserine (PS) asymmetry and endocytic transport. In chat-1 and tat-1
      mutants, the endocytic sorting process is disrupted, leading to defects in both
      cargo recycling and degradation. TAT-1 and CHAT-1 colocalize to the tubular
      domain of the early endosome, the tubular endocytic recycling compartment (ERC),
      and the recycling endosome where PS is enriched on the cytosolic surface. Loss of
      tat-1 and chat-1 function disrupts membrane PS asymmetry and abrogates the
      tubular membrane structure. Our data suggest that CHAT-1 and TAT-1 maintain
      membrane phosphatidylserine asymmetry, thus promoting membrane tubulation and
      regulating endocytic sorting and recycling.

PMID- 21170359
TI  - The C-terminal domain of the bacterial SSB protein acts as a DNA maintenance hub
      at active chromosome replication forks.
AB  - We have investigated in vivo the role of the carboxy-terminal domain of the
      Bacillus subtilis Single-Stranded DNA Binding protein (SSB(Cter)) as a
      recruitment platform at active chromosomal forks for many proteins of the genome
      maintenance machineries. We probed this SSB(Cter) interactome using GFP fusions
      and by Tap-tag and biochemical analysis. It includes at least 12 proteins. The
      interactome was previously shown to include PriA, RecG, and RecQ and extended in
      this study by addition of DnaE, SbcC, RarA, RecJ, RecO, XseA, Ung, YpbB, and
      YrrC. Targeting of YpbB to active forks appears to depend on RecS, a RecQ
      paralogue, with which it forms a stable complex. Most of these SSB partners are
      conserved in bacteria, while others, such as the essential DNA polymerase DnaE,
      YrrC, and the YpbB/RecS complex, appear to be specific to B. subtilis. SSB(Cter)
      deletion has a moderate impact on B. subtilis cell growth. However, it markedly
      affects the efficiency of repair of damaged genomic DNA and arrested replication
      forks. ssbDeltaCter mutant cells appear deficient in RecA loading on ssDNA,
      explaining their inefficiency in triggering the SOS response upon exposure to
      genotoxic agents. Together, our findings show that the bacterial SSB(Cter) acts
      as a DNA maintenance hub at active chromosomal forks that secures their
      propagation along the genome.

PMID- 21170360
TI  - HIV capsid is a tractable target for small molecule therapeutic intervention.
AB  - Despite a high current standard of care in antiretroviral therapy for HIV,
      multidrug-resistant strains continue to emerge, underscoring the need for
      additional novel mechanism inhibitors that will offer expanded therapeutic
      options in the clinic. We report a new class of small molecule antiretroviral
      compounds that directly target HIV-1 capsid (CA) via a novel mechanism of action.
      The compounds exhibit potent antiviral activity against HIV-1 laboratory strains,
      clinical isolates, and HIV-2, and inhibit both early and late events in the viral
      replication cycle. We present mechanistic studies indicating that these early and
      late activities result from the compound affecting viral uncoating and assembly,
      respectively. We show that amino acid substitutions in the N-terminal domain of
      HIV-1 CA are sufficient to confer resistance to this class of compounds,
      identifying CA as the target in infected cells. A high-resolution co-crystal
      structure of the compound bound to HIV-1 CA reveals a novel binding pocket in the
      N-terminal domain of the protein. Our data demonstrate that broad-spectrum
      antiviral activity can be achieved by targeting this new binding site and reveal
      HIV CA as a tractable drug target for HIV therapy.

PMID- 21170362
TI  - Recent advances in pharmacological treatment of neuropathic pain.
AB  - Recent studies investigating the pharmacological management of neuropathic pain
      support the efficacy of certain antidepressants, anticonvulsants, and opioids.
      Novel directions in drug applications include topical applications of patches
      with either lidocaine or capsaicin and intradermal injections of botulinum toxin.
      In cases of partial pain relief, drug combinations may be considered.

PMID- 21170361
TI  - Identification of Y-box binding protein 1 as a core regulator of MEK/ERK pathway
      dependent gene signatures in colorectal cancer cells.
AB  - Transcriptional signatures are an indispensible source of correlative information
      on disease-related molecular alterations on a genome-wide level. Numerous
      candidate genes involved in disease and in factors of predictive, as well as of
      prognostic, value have been deduced from such molecular portraits, e.g. in
      cancer. However, mechanistic insights into the regulatory principles governing
      global transcriptional changes are lagging behind extensive compilations of
      deregulated genes. To identify regulators of transcriptome alterations, we used
      an integrated approach combining transcriptional profiling of colorectal cancer
      cell lines treated with inhibitors targeting the receptor tyrosine kinase
      (RTK)/RAS/mitogen-activated protein kinase pathway, computational prediction of
      regulatory elements in promoters of co-regulated genes, chromatin-based and
      functional cellular assays. We identified commonly co-regulated, proliferation
      associated target genes that respond to the MAPK pathway. We recognized E2F and
      NFY transcription factor binding sites as prevalent motifs in those pathway
      responsive genes and confirmed the predicted regulatory role of Y-box binding
      protein 1 (YBX1) by reporter gene, gel shift, and chromatin immunoprecipitation
      assays. We also validated the MAPK-dependent gene signature in colorectal cancers
      and provided evidence for the association of YBX1 with poor prognosis in
      colorectal cancer patients. This suggests that MEK/ERK-dependent, YBX1-regulated
      target genes are involved in executing malignant properties.

PMID- 21170363
TI  - Adhesion of rhomboid lip to lower cranial nerves as special consideration in
      microvascular decompression for hemifacial spasm: Report of two cases.
AB  - BACKGROUND: Although the rhomboid lip is a well-known structure constructing the
      foramen of Luschka, less attention has been directed to the structure for
      posterior fossa microsurgeries. The authors report two cases of the hemifacial
      spasm (HFS) with a large rhomboid lip, focusing on the importance of the
      structure during microvascular decompression. CASE DESCRIPTION: A 59-year-old
      female presenting with left HFS was admitted to our hospital. A preoperative
      magnetic resonance image demonstrated an offending artery at the root exit zone
      of the VII nerve. The patient underwent microvascular decompression through the
      lateral suboccipital approach. The intraoperative findings showed that a large
      rhomboid lip adhered to the IX and X cranial nerves and prevented the exposure of
      the root exit zone of the VII cranial nerve. The rhomboid lip was meticulously
      separated from the cranial nerves so that the choroid plexus of the foramen of
      Luschka and the rhomboid lip could be safely lifted with a spatula, and the
      offending artery was successfully detached from the root exit zone. In another
      case of a 60-year-old male, the rhomboid lip was so large that it needed to be
      incised before separating it from the lower cranial nerves. In each case, the HFS
      was resolved following surgery without any new deficits. CONCLUSION: The large
      rhomboid lip adhering to the cranial nerves should be given more attention in the
      posterior fossa surgeries and should be managed based on the microsurgical
      anatomy for preventing unexpected lower cranial nerve deficit.

PMID- 21170364
TI  - Magnetic resonance findings in sellar and suprasellar tuberculoma with
      hemorrhage.
AB  - BACKGROUND: Tuberculosis is endemic in many counteries like India. It can infect
      any site in the central nervous system. However, islolated involvement of the
      sellar and suprasellar region is rare. Sellar tuberculoma with hemorrhage is even
      more rare. We present magnetic resonance (MR) findings in case of sellar and
      suprasellar tuberculoma with hemorrhage. CASE DESCRIPTION: A 40-year-old female
      patient presented with a 1-month history of persistent headache and blurred
      vision on the left side. A contrast-enhanced MR study revealed peripherally
      enhancing sellar and suprasellar mass with hemorrhage with compression of the
      left half of the optic chiasma. There was also evidence of infundibular
      thickening and enhancement of the adjacent dura. The mass was approached through
      a transphenoidal approach and was partially resected. Subsequent histopathology
      was suggestive of tuberculosis. The patient was put on anti-tubercular therapy.
      Patient reported significant improvement in symptoms. Follow-up MR done 8 months
      later confirmed complete regression of the mass. CONCLUSION: Because of its
      rarity, sellar tuberculoma is seldom considered in the differential diagnosis and
      is often mistaken for pituitary macroadenoma, which is the most common tumor in
      this region. Although rare, presence of infundibular thickening and enhancement
      of the adjacent dura should suggest the presence of a granulomatous lesion like
      tuberculoma.

PMID- 21170365
TI  - A new polyvinyl alcohol hydrogel vascular model (KEZLEX) for microvascular
      anastomosis training.
AB  - BACKGROUND: Microvascular anastomosis is a challenging neurosurgical technique
      that requires extensive training for one to master it. We developed a new
      vascular model (KEZLEX, Ono and Co., Ltd., Tokyo, Japan) as a non-animal,
      realistic tool for practicing microvascular anastomosis under realistic
      circumstances. METHODS: The model was manufactured from polyvinyl alcohol
      hydrogel to provide 1.0-3.0 mm diameter (available for 0.5-mm pitch), 6-8 cm long
      tubes that have qualitatively similar surface characteristics, visibility, and
      stiffness to human donor and recipient arteries for various bypass surgeries
      based on three-dimensional computed tomography/magnetic resonance imaging
      scanning data reconstruction using visible human data set and vessel casts.
      RESULTS: Trainees can acquire basic microsuturing techniques for end-to-end, end
      to-side, and side-to-side anastomoses with handling similar to that for real
      arteries. To practice standard deep bypass techniques under realistic
      circumstances, the substitute vessel can be fixed to specific locations of a
      commercially available brain model with pins. CONCLUSION: Our vascular prosthesis
      model is simple and easy to set up for repeated practice, and will contribute to
      facilitate "off-the-job" training by trainees.

PMID- 21170366
TI  - Cerebral and somatic venous oximetry in adults and infants.
AB  - BACKGROUND: The development in the last decade of noninvasive, near infrared
      spectroscopy (NIRS) analysis of tissue hemoglobin saturation in vivo has provided
      a new and dramatic tool for the management of hemodynamics, allowing early
      detection and correction of imbalances in oxygen delivery to the brain and vital
      organs. DESCRIPTION: The theory and validation of NIRS and its clinical use are
      reviewed. Studies are cited documenting tissue penetration and response to
      various physiologic and pharmacologic mechanisms resulting in changes in oxygen
      delivery and blood flow to the organs and brain as reflected in the regional
      hemoglobin oxygen saturation (rSO(2)). The accuracy of rSO(2) readings and the
      clinical use of NIRS in cardiac surgery and intensive care in adults, children
      and infants are discussed. CONCLUSIONS: Clinical studies have demonstrated that
      NIRS can improve outcome and enhance patient management, avoiding postoperative
      morbidities and potentially preventing catastrophic outcomes.

PMID- 21170367
TI  - Resolution of immune thrombocytopenic purpura associated with extranodal B-cell
      lymphoma of the petroclival region after radiotherapy.
AB  - BACKGROUND: Secondary immune thrombocytopenic purpura (ITP) associated with
      extranodal B-cell non-Hodgkin's lymphoma (NHL) is extremely rare. The optimal
      management is not established. We report a first case of ITP in association with
      extranodal B-cell NHL originating in the lower petroclival region, successfully
      managed by local tumor control using conventional radiotherapy. CASE DESCRIPTION:
      A 75-year-old man presented with a two-month history of hearing loss, hoarseness,
      and dysphagia. Neuroimaging revealed a large enhanced lesion in the left lower
      petroclival bone near the jugular foramen. Isolated unilateral parotid
      lymphadenopathy was also noted. Preoperative laboratory findings were normal,
      except for elevation of serum soluble interleukin-2 receptor level. A
      suboccipital craniotomy was performed and a biopsy sample was taken. Histological
      and immunohistochemical examination confirmed small B-cell lymphoma with
      plasmacytic differentiation. After initiation of radiotherapy, thrombocytopenia
      (24,000/ul) rapidly developed. Serological and bone marrow examination confirmed
      ITP. Prednisone was given at 1 mg/kg/day and radiation therapy was continued.
      After more than 32Gy, platelet count rapidly normalized. Radiotherapy to the
      tumor site achieved local tumor control and ITP was resolved. No evidence of
      recurrence and normal platelet count were confirmed at the two-year follow-up
      examination. CONCLUSION: Local control of the tumor was considered important in
      the resolution of secondary ITP in association with extranodal NHL of the skull
      base region.

PMID- 21170368
TI  - Recent advances in using propofol by non-anesthesiologists.
AB  - Evidence is accumulating that non-anesthesiologist-administered propofol (NAAP)
      sedation has a safety and efficacy profile comparable or superior to that
      provided by benzodiazepines with or without opioids. The guidelines currently
      available emphasize the importance of appropriate patient selection, staff
      training, monitoring, and low-dose sedation protocols for NAAP safety. In
      addition, capnograph monitoring and computer-assisted sedation systems may
      further improve patient safety during NAAP.

PMID- 21170369
TI  - Fibrosis: recent advances in myofibroblast biology and new therapeutic
      perspectives.
AB  - The crucial role of the myofibroblast in wound healing and fibrosis development
      is well established. This review discusses the mechanisms of myofibroblast action
      and the new findings that may develop into therapeutic strategies during the next
      few years.

PMID- 21170370
TI  - Vaccination and infection prevention in inflammatory bowel disease.
AB  - The current medical therapy used in Crohn's disease and ulcerative colitis
      comprises drugs that interfere with immune response and therefore caution is
      needed for infectious side effects, and where possible, strategies to prevent
      their occurrence should be undertaken. Last year, international consensus
      guidelines on this topic were published by the European Crohn's and Colitis
      Organisation.

PMID- 21170371
TI  - When should antiretroviral therapy be started in HIV-positive persons?
AB  - Recommendations for the initiation of combination antiretroviral therapy in HIV
      positive individuals are largely based on data from observational studies. Whilst
      all guidelines recommend immediate treatment in individuals with a CD4 count of
      less than 350 cells/mm(3), guidelines vary in their recommendations for treatment
      at higher CD4 counts. Several large cohort studies have published findings that
      contribute to the debate, although conclusions vary and results from these
      studies may be subject to bias.

PMID- 21170372
TI  - Developments in low-resolution biological X-ray crystallography.
AB  - Despite the recent substantial technological developments in X-ray
      crystallography, solving and refining structures at low resolutions remain
      substantial challenges. Many macromolecular crystals, especially those of large
      molecules or multicomponent assemblies, diffract X-rays to resolutions that are
      worse than 3.5A. This report summarizes several recent advances aiding low
      resolution crystallographic work.

PMID- 21170373
TI  - The use of antenatal magnesium sulfate for neuroprotection for infants born
      prematurely.
AB  - Cerebral palsy occurs in three to four infants per 1000 live births. Preterm
      birth prior to 34 weeks' gestation is a major risk factor. Five randomized
      controlled trials of antenatal magnesium sulfate (MgSO(4)) found a trend of
      reduced risk of cerebral palsy and mortality in preterm infants. Three meta
      analyses using the data from the five randomized controlled trials, which
      included a total of 5235 prospectively evaluated fetuses, found that MgSO(4)
      given to women at risk of premature birth significantly reduced the risk of
      cerebral palsy by 30% without increasing the risk of perinatal or infant death.
      The implication for clinical practice is that MgSO(4) should be considered for
      use in patients at high risk of delivery before 34 weeks' gestation.

PMID- 21170374
TI  - The role of microRNAs in acute myeloid leukemia.
AB  - MicroRNAs (miRs) are short (18-22 nucleotides) non-coding RNAs that are important
      in regulating gene expression. MiR expression is deregulated in many types of
      cancers, including leukemias. In acute myeloid leukemia (AML), the expression of
      specific miRs has been linked with both prognostically and cytogenetically
      defined subgroups. Recent studies have shown that deregulation of miR expression
      is not simply a consequence of AML but a potential contributer to leukemogenesis.
      This commentary will focus on select findings that describe the different
      mechanistic roles for miRs in the development of leukemia.

PMID- 21170375
TI  - Genetic screening for metabolic and age-related complications in HIV-infected
      persons.
AB  - Genetic screening for HIV-related complications is emerging as a clinically
      relevant prediction tool. A number of single nucleotide polymorphisms associated
      with conditions such as dyslipidemia and type 2 diabetes have been identified in
      both the general population and in HIV-infected individuals. Additionally, genome
      wide association studies have looked at hepatitis C susceptibility in HIV
      infected people, and genetic studies are ongoing for coronary artery disease,
      osteoporosis, and neurocognitive dysfunction. To date, understanding the
      contribution of genetic variation to the pathogenesis of lipoatrophy and kidney
      disease in HIV-infection is limited.

PMID- 21170376
TI  - Recent advances in management of cryptococcal meningitis: commentary.
AB  - Cryptococcal meningitis remains a substantial health burden with high morbidity,
      particularly in developing countries. Antifungal treatment regimens are guided by
      host factors, severity of illness (including presence of complications), and
      causative cryptococcal species. Recent clinical studies indicate the need for
      rapidly fungicidal induction therapy regimens using amphotericin B in combination
      with flucytosine for optimal outcomes. Maintenance therapy with fluconazole is
      necessary until recovery of immune function. Cryptococcus gattii meningitis
      requires prolonged induction/eradication therapy. Prompt control of raised
      intracranial pressure or hydrocephalus is essential. Clinicians should be
      vigilant for immune restoration-like features. Adjuvant surgery, corticosteroids,
      and/or recombinant interferon-gamma may be required for large cryptococcomas,
      cerebral edema, or refractory infection.

PMID- 21170377
TI  - Matrix metalloproteinase 1: role in sarcoma biology.
AB  - In carcinomas stromal cells participate in cancer progression by producing
      proteases such as MMPs. The expression MMP1 is a prognostic factor in human
      chondrosarcoma, however the role in tumor progression is unknown. Laser capture
      microdissection and In Situ hybridization were used to determine cellular origin
      of MMP1 in human sarcomas. A xenogenic model of tumor progression was then used
      and mice were divided in two groups: each harboring either the control or a
      stably MMP1 silenced cell line. Animals were sacrificed; the neovascularization,
      primary tumor volumes, and metastatic burden were assessed. LCM and RNA-ISH
      analysis revealed MMP1 expression was predominantly localized to the tumor cells
      in all samples of sarcoma (p = 0.05). The percentage lung metastatic volume at 5
      weeks (p = 0.08) and number of spontaneous deaths secondary to systemic tumor
      burden were lower in MMP1 silenced cell bearing mice. Interestingly, this group
      also demonstrated a larger primary tumor size (p<0.04) and increased angiogenesis
      (p<0.01). These findings were found to be consistent when experiment was repeated
      using a second independent MMP1 silencing sequence. Prior clinical trials
      employing MMP1 inhibitors failed because of a poor understanding of the role of
      MMPs in tumor progression. The current findings indicating tumor cell production
      of MMP1 by sarcoma cells is novel and highlights the fundamental differences in
      MMP biology between carcinomas and sarcomas. The results also emphasize the
      complex roles of MMP in tumor progression of sarcomas. Not only does metastasis
      seem to be affected by MMP1 silencing, but also local tumor growth and
      angiogenesis are affected inversely.

PMID- 21170378
TI  - Humans and insects decide in similar ways.
AB  - Behavioral ecologists assume that animals use a motivational mechanism for
      decisions such as action selection and time allocation, allowing the maximization
      of their fitness. They consider both the proximate and ultimate causes of
      behavior in order to understand this type of decision-making in animals.
      Experimental psychologists and neuroeconomists also study how agents make
      decisions but they consider the proximate causes of the behavior. In the case of
      patch-leaving, motivation-based decision-making remains simple speculation. In
      contrast to other animals, human beings can assess and evaluate their own
      motivation by an introspection process. It is then possible to study the declared
      motivation of humans during decision-making and discuss the mechanism used as
      well as its evolutionary significance. In this study, we combine both the
      proximate and ultimate causes of behavior for a better understanding of the human
      decision-making process. We show for the first time ever that human subjects use
      a motivational mechanism similar to small insects such as parasitoids and
      bumblebees to decide when to leave a patch. This result is relevant for
      behavioral ecologists as it supports the biological realism of this mechanism.
      Humans seem to use a motivational mechanism of decision making known to be
      adaptive to a heterogeneously distributed resource. As hypothesized by Hutchinson
      et al. and Wilke and Todd, our results are consistent with the evolutionary
      shaping of decision making because hominoids were hunters and gatherers on food
      patches for more than two million years. We discuss the plausibility of a neural
      basis for the motivation mechanism highlighted here, bridging the gap between
      behavioral ecology and neuroeconomy. Thus, both the motivational mechanism
      observed here and the neuroeconomy findings are most likely adaptations that were
      selected for during ancestral times.

PMID- 21170379
TI  - Prolonged survival of allografts induced by mycobacterial Hsp70 is dependent on
      CD4+CD25+ regulatory T cells.
AB  - BACKGROUND: Heat shock proteins (Hsps) are stress induced proteins with
      immunomodulatory properties. The Hsp70 of Mycobacterium tuberculosis (TBHsp70)
      has been shown to have an anti-inflammatory role on rodent autoimmune arthritis
      models, and the protective effects were demonstrated to be dependent on
      interleukin-10 (IL-10). We have previously observed that TBHsp70 inhibited
      maturation of dendritic cells (DCs) and induced IL-10 production by these cells,
      as well as in synovial fluid cells. METHODOLOGY/PRINCIPAL FINDINGS: We
      investigated if TBHsp70 could inhibit allograft rejection in two murine allograft
      systems, a transplanted allogeneic melanoma and a regular skin allograft. In both
      systems, treatment with TBHsp70 significantly inhibited rejection of the graft,
      and correlated with regulatory T cells (Tregs) recruitment. This effect was not
      tumor mediated because injection of TBHsp70 in tumor-free mice induced an
      increase of Tregs in the draining lymph nodes as well as inhibition of
      proliferation of lymph node T cells and an increase in IL-10 production. Finally,
      TBHsp70 inhibited skin allograft acute rejection, and depletion of Tregs using a
      monoclonal antibody completely abolished this effect. CONCLUSIONS/SIGNIFICANCE:
      We present the first evidence for an immunosuppressive role for this protein in a
      graft rejection system, using an innovative approach--immersion of the graft
      tissue in TBHsp70 solution instead of protein injection. Also, this is the first
      study that demonstrates dependence on Treg cells for the immunosuppressive role
      of TBHsp70. This finding is relevant for the elucidation of the immunomodulatory
      mechanism of TBHsp70. We propose that this protein can be used not only for
      chronic inflammatory diseases, but is also useful for organ transplantation
      management.

PMID- 21170381
TI  - Declining sleep quality among nurses: a population-based four-year longitudinal
      study on the transition from nursing education to working life.
AB  - BACKGROUND: Several studies have established impaired sleep is a common problem
      among nurses. Overworked, fatigued and stressed nurses are at a higher risk of
      making mistakes that threaten patient safety as well as their own health. The aim
      of the present study was to longitudinally monitor the development of sleep
      quality in nurses, starting from the last semester at the university, with three
      subsequent annual follow-ups once the nurses had entered working life.
      METHODOLOGY/PRINCIPAL FINDINGS: Nationwide, longitudinal questionnaire study of
      nursing students and newly qualified nurses in Sweden. The results imply a
      continuous decline in sleep quality among nurses during the three years of follow
      up, starting from their last semester of nursing education and continuing for
      three years into their working life. The most pronounced short-term decline in
      sleep quality seems to occur in the transition between student life and working
      life. CONCLUSION/SIGNIFICANCE: This finding is important since it may affect the
      quality of care and the health of nurses negatively.

PMID- 21170380
TI  - Elevated pressure improves the extraction and identification of proteins
      recovered from formalin-fixed, paraffin-embedded tissue surrogates.
AB  - BACKGROUND: Proteomic studies of formalin-fixed paraffin-embedded (FFPE) tissues
      are frustrated by the inability to extract proteins from archival tissue in a
      form suitable for analysis by 2-D gel electrophoresis or mass spectrometry. This
      inability arises from the difficulty of reversing formaldehyde-induced protein
      adducts and cross-links within FFPE tissues. We previously reported the use of
      elevated hydrostatic pressure as a method for efficient protein recovery from a
      hen egg-white lysozyme tissue surrogate, a model system developed to study
      formalin fixation and histochemical processing. PRINCIPAL FINDINGS: In this
      study, we demonstrate the utility of elevated hydrostatic pressure as a method
      for efficient protein recovery from FFPE mouse liver tissue and a complex multi
      protein FFPE tissue surrogate comprised of hen egg-white lysozyme, bovine
      carbonic anhydrase, bovine ribonuclease A, bovine serum albumin, and equine
      myoglobin (55?15?15?10?5 wt%). Mass spectrometry of the FFPE tissue surrogates
      retrieved under elevated pressure showed that both the low and high-abundance
      proteins were identified with sequence coverage comparable to that of the
      surrogate mixture prior to formaldehyde treatment. In contrast, non-pressure
      extracted tissue surrogate samples yielded few positive and many false peptide
      identifications. Studies with soluble formalin-treated bovine ribonuclease A
      demonstrated that pressure modestly inhibited the rate of reversal (hydrolysis)
      of formaldehyde-induced protein cross-links. Dynamic light scattering studies
      suggest that elevated hydrostatic pressure and heat facilitate the recovery of
      proteins free of formaldehyde adducts and cross-links by promoting protein
      unfolding and hydration with a concomitant reduction in the average size of the
      protein aggregates. CONCLUSIONS: These studies demonstrate that elevated
      hydrostatic pressure treatment is a promising approach for improving the recovery
      of proteins from FFPE tissues in a form suitable for proteomic analysis.

PMID- 21170383
TI  - The structure of the EU mediasphere.
AB  - BACKGROUND: A trend towards automation of scientific research has recently
      resulted in what has been termed "data-driven inquiry" in various disciplines,
      including physics and biology. The automation of many tasks has been identified
      as a possible future also for the humanities and the social sciences,
      particularly in those disciplines concerned with the analysis of text, due to the
      recent availability of millions of books and news articles in digital format. In
      the social sciences, the analysis of news media is done largely by hand and in a
      hypothesis-driven fashion: the scholar needs to formulate a very specific
      assumption about the patterns that might be in the data, and then set out to
      verify if they are present or not. METHODOLOGY/PRINCIPAL FINDINGS: In this study,
      we report what we think is the first large scale content-analysis of cross
      linguistic text in the social sciences, by using various artificial intelligence
      techniques. We analyse 1.3 M news articles in 22 languages detecting a clear
      structure in the choice of stories covered by the various outlets. This is
      significantly affected by objective national, geographic, economic and cultural
      relations among outlets and countries, e.g., outlets from countries sharing
      strong economic ties are more likely to cover the same stories. We also show that
      the deviation from average content is significantly correlated with membership to
      the eurozone, as well as with the year of accession to the EU.
      CONCLUSIONS/SIGNIFICANCE: While independently making a multitude of small
      editorial decisions, the leading media of the 27 EU countries, over a period of
      six months, shaped the contents of the EU mediasphere in a way that reflects its
      deep geographic, economic and cultural relations. Detecting these subtle signals
      in a statistically rigorous way would be out of the reach of traditional methods.
      This analysis demonstrates the power of the available methods for significant
      automation of media content analysis.

PMID- 21170382
TI  - Alanine aminotransferase decreases with age: the Rancho Bernardo Study.
AB  - BACKGROUND: Serum alanine aminotransferase (ALT) is a marker of liver injury. The
      2005 American Gastroenterology Association Future Trends Committee report states
      that serum ALT levels remain constant with age. This study examines the
      association between serum ALT and age in a community-dwelling cohort in the
      United States. METHODS: A cross-sectional study of 2,364 (54% female)
      participants aged 30-93 years from the Rancho Bernardo Study cohort who attended
      a research clinic visit in 1984-87. Demographic, metabolic co-variates, ALT,
      bilirubin, gamma glutamyl transferase (GGT), albumin, and adiposity signaling
      biomarkers (leptin, IL-6, adiponectin, ghrelin) were measured. Participants were
      divided into four-groups based upon age quartile, and multivariable-adjusted
      least squares of means (LSM) were examined (p for trend <0.05). RESULTS: ALT
      decreased with increasing age, with mean ALT levels (IU/L) of 23, 21, 20, and 17
      for those between quartile ages 30-62, 63-71, 72-77, and 78-93 years (p<0.0001).
      Trends of decreasing LSM ALT with age and the decreasing prevalence of
      categorically defined elevated serum ALT with age remained robust after adjusting
      for sex, alcohol use, metabolic syndrome components, and biomarkers of adiposity
      (p-value <0.0001), and was not materially changed after adjusting for bilirubin,
      GGT, and albumin. CONCLUSIONS: ALT levels decrease with age in both men and women
      independent of metabolic syndrome components, adiposity signaling biomarkers, and
      other commonly used liver function tests. Further studies are needed to
      understand the mechanisms responsible for a decline in ALT with age, and to
      establish the optimal cut-point of normal ALT in the elderly.

PMID- 21170385
TI  - Hepatitis C virus core protein abrogates the DDX3 function that enhances IPS-1
      mediated IFN-beta induction.
AB  - The DEAD box helicase DDX3 assembles IPS-1 (also called Cardif, MAVS, or VISA) in
      non-infected human cells where minimal amounts of the RIG-I-like receptor (RLR)
      protein are expressed. DDX3 C-terminal regions directly bind the IPS-1 CARD-like
      domain as well as the N-terminal hepatitis C virus (HCV) core protein. DDX3
      physically binds viral RNA to form IPS-1-containing spots, that are visible by
      confocal microscopy. HCV polyU/UC induced IPS-1-mediated interferon (IFN)-beta
      promoter activation, which was augmented by co-transfected DDX3. DDX3 spots
      localized near the lipid droplets (LDs) where HCV particles were generated. Here,
      we report that HCV core protein interferes with DDX3-enhanced IPS-1 signaling in
      HEK293 cells and in hepatocyte Oc cells. Unlike the DEAD box helicases RIG-I and
      MDA5, DDX3 was constitutively expressed and colocalized with IPS-1 around
      mitochondria. In hepatocytes (O cells) with the HCV replicon, however, DDX3/IPS-1
      enhanced IFN-beta-induction was largely abrogated even when DDX3 was co
      expressed. DDX3 spots barely merged with IPS-1, and partly assembled in the HCV
      core protein located near the LD in O cells, though in some O cells IPS-1 was
      diminished or disseminated apart from mitochondria. Expression of DDX3 in
      replicon-negative or core-less replicon-positive cells failed to cause complex
      formation or LD association. HCV core protein and DDX3 partially colocalized only
      in replicon-expressing cells. Since the HCV core protein has been reported to
      promote HCV replication through binding to DDX3, the core protein appears to
      switch DDX3 from an IFN-inducing mode to an HCV-replication mode. The results
      enable us to conclude that HCV infection is promoted by modulating the dual
      function of DDX3.

PMID- 21170384
TI  - Depression and HIV in Botswana: a population-based study on gender-specific
      socioeconomic and behavioral correlates.
AB  - BACKGROUND: Depression is a leading contributor to the burden of disease
      worldwide, a critical barrier to HIV prevention and a common serious HIV co
      morbidity. However, depression screening and treatment are limited in sub-Saharan
      Africa, and there are few population-level studies examining the prevalence and
      gender-specific factors associated with depression. METHODS: We conducted a cross
      sectional population-based study of 18-49 year-old adults from five districts in
      Botswana with the highest prevalence of HIV-infection. We examined the prevalence
      of depressive symptoms, using a Hopkins Symptom Checklist for Depression (HSCL-D)
      score of >= 1.75 to define depression, and correlates of depression using
      multivariate logistic regression stratified by sex. RESULTS: Of 1,268
      participants surveyed, 25.3% of women and 31.4% of men had depression. Among
      women, lower education (adjusted odds ratio [AOR] 2.07, 95% confidence interval
      [1.30-3.32]), higher income (1.77 [1.09-2.86]), and lack of control in sexual
      decision-making (2.35 [1.46-3.81]) were positively associated with depression.
      Among men, being single (1.95 [1.02-3.74]), living in a rural area (1.63 [1.02
      2.65]), having frequent visits to a health provider (3.29 [1.88-5.74]),
      anticipated HIV stigma (fearing discrimination if HIV status was revealed) (2.04
      [1.27-3.29]), and intergenerational sex (2.28 [1.17-4.41]) were independently
      associated with depression. DISCUSSION: Depression is highly prevalent in
      Botswana, and its correlates are gender-specific. Our findings suggest multiple
      targets for screening and prevention of depression and highlight the need to
      integrate mental health counseling and treatment into primary health care to
      decrease morbidity and improve HIV management efforts.

PMID- 21170387
TI  - Utility of quantitative sensory testing and screening tools in identifying HIV
      associated peripheral neuropathy in Western Kenya: pilot testing.
AB  - BACKGROUND/AIM: Neuropathy is the most common neurologic complication of HIV but
      is widely under-diagnosed in resource-constrained settings. We aimed to identify
      tools that accurately distinguish individuals with moderate/severe peripheral
      neuropathy and can be administered by non-physician healthcare workers (HCW) in
      resource-constrained settings. METHODS: We enrolled a convenience sample of 30
      HIV-infected outpatients from a Kenyan HIV-care clinic. A HCW administered the
      Neuropathy Severity Score (NSS), Single Question Neuropathy Screen (Single-QNS),
      Subjective Peripheral Neuropathy Screen (Subjective-PNS), and Brief Peripheral
      Neuropathy Screen (Brief-PNS). Monofilament, graduated tuning fork, and two-point
      discrimination examinations were performed. Tools were validated against a
      neurologist's clinical assessment of moderate/severe neuropathy. RESULTS: The
      sample was 57% male, mean age 38.6 years, and mean CD4 count 324 cells/uL.
      Neurologist's assessment identified 20% (6/30) with moderate/severe neuropathy.
      Diagnostic utilities for moderate/severe neuropathy were: Single-QNS--83%
      sensitivity, 71% specificity; Subjective-PNS-total--83% sensitivity, 83%
      specificity; Subjective-PNS-max and NSS--67% sensitivity, 92% specificity; Brief
      PNS--0% sensitivity, 92% specificity; monofilament--100% sensitivity, 88%
      specificity; graduated tuning fork--83% sensitivity, 88% specificity; two-point
      discrimination--75% sensitivity, 58% specificity. CONCLUSIONS: Pilot testing
      suggests Single-QNS, Subjective-PNS, and monofilament examination accurately
      identify HIV-infected patients with moderate/severe neuropathy and may be useful
      diagnostic tools in resource-constrained settings.

PMID- 21170386
TI  - Kinome profiling reveals an interaction between jasmonate, salicylate and light
      control of hyponastic petiole growth in Arabidopsis thaliana.
AB  - Plants defend themselves against infection by biotic attackers by producing
      distinct phytohormones. Especially jasmonic acid (JA) and salicylic acid (SA) are
      well known defense-inducing hormones. Here, the effects of MeJA and SA on the
      Arabidopsis thaliana kinome were monitored using PepChip arrays containing kinase
      substrate peptides to analyze posttranslational interactions in MeJA and SA
      signaling pathways and to test if kinome profiling can provide leads to predict
      posttranslational events in plant signaling. MeJA and SA mediate differential
      phosphorylation of substrates for many kinase families. Also some plant specific
      substrates were differentially phosphorylated, including peptides derived from
      Phytochrome A, and Photosystem II D protein. This indicates that MeJA and SA
      mediate cross-talk between defense signaling and light responses. We tested the
      predicted effects of MeJA and SA using light-mediated upward leaf movement
      (differential petiole growth also called hyponastic growth). We found that MeJA,
      infestation by the JA-inducing insect herbivore Pieris rapae, and SA suppressed
      low light-induced hyponastic growth. MeJA and SA acted in a synergistic fashion
      via two (partially) divergent signaling routes. This work demonstrates that
      kinome profiling using PepChip arrays can be a valuable complementary ~omics tool
      to give directions towards predicting behavior of organisms after a given
      stimulus and can be used to obtain leads for physiological relevant phenomena in
      planta.

PMID- 21170388
TI  - Endothelial surface layer degradation by chronic hyaluronidase infusion induces
      proteinuria in apolipoprotein E-deficient mice.
AB  - OBJECTIVE: Functional studies show that disruption of endothelial surface layer
      (ESL) is accompanied by enhanced sensitivity of the vasculature towards
      atherogenic stimuli. However, relevance of ESL disruption as causal mechanism for
      vascular dysfunction remains to be demonstrated. We examined if loss of ESL
      through enzymatic degradation would affect vascular barrier properties in an
      atherogenic model. METHODS: Eight week old male apolipoprotein E deficient mice
      on Western-type diet for 10 weeks received continuous active or heat-inactivated
      hyaluronidase (10 U/hr, i.v.) through an osmotic minipump during 4 weeks. Blood
      chemistry and anatomic changes in both macrovasculature and kidneys were
      examined. RESULTS: Infusion with active hyaluronidase resulted in decreased ESL
      (0.32+/-0.22 mL) and plasma volume (1.03+/-0.18 mL) compared to inactivated
      hyaluronidase (0.52+/-0.29 mL and 1.28+/-0.08 mL, p<0.05 respectively).Active
      hyaluronidase increased proteinuria compared to inactive hyaluronidase (0.27+/
      0.02 vs. 0.15+/-0.01 ug/ug protein/creatinin, p<0.05) without changes in
      glomerular morphology or development of tubulo-interstitial inflammation.
      Atherosclerotic lesions in the aortic branches showed increased matrix production
      (collagen, 32+/-5 vs. 18+/-3%; glycosaminoglycans, 11+/-5 vs. 0.1+/-0.01%, active
      vs. inactive hyaluronidase, p<0.05). CONCLUSION: ESL degradation in apoE
      deficient mice contributes to reduced increased urinary protein excretion without
      significant changes in renal morphology. Second, the induction of compositional
      changes in atherogenic plaques by hyaluronidase point towards increased plaque
      vulnerability. These findings support further efforts to evaluate whether ESL
      restoration is a valuable target to prevent (micro) vascular disease progression.

PMID- 21170389
TI  - No association between HIV and intimate partner violence among women in 10
      developing countries.
AB  - BACKGROUND: Intimate Partner Violence (IPV) has been reported to be a determinant
      of women's risk for HIV. We examined the relationship between women's self
      reported experiences of IPV in their most recent relationship and their
      laboratory-confirmed HIV serostatus in ten low- to middle-income countries.
      METHODOLOGY/PRINCIPAL FINDINGS: Data for the study came from the most recent
      Demographic and Health Surveys conducted in Dominican Republic, Haiti, India,
      Kenya, Liberia, Malawi, Mali, Rwanda, Zambia and Zimbabwe. Each survey population
      was a cross-sectional sample of women aged 15-49 years. Information on IPV was
      obtained by a face-to-face interview with the mother with an 81.1% response rate;
      information on HIV serostatus was obtained from blood samples with an 85.3%
      response rate. Demographic and socioeconomic variables were considered as
      potentially confounding covariates. Logistic regression models accounting for
      multi-stage survey design were estimated individually for each country and as a
      pooled total with country fixed effects (n = 60,114). Country-specific adjusted
      odds ratios (OR) for physical or sexual IPV compared to neither ranged from 0.45
      [95% confidence interval (CI): 0.23-0.90] in Haiti to 1.35 [95% CI: 0.95-1.90] in
      India; the pooled association was 1.03 [95% CI: 0.94-1.13]. Country-specific
      adjusted ORs for physical and sexual IPV compared to no sexual IPV ranged from
      0.41 [95% CI: 0.12-1.36] in Haiti to 1.41 [95% CI: 0.26-7.77] in Mali; the pooled
      association was 1.05 [95% CI: 0.90-1.22]. CONCLUSIONS: IPV and HIV were not found
      to be consistently associated amongst ever-married women in national population
      samples in these lower income countries, suggesting that IPV is not consistently
      associated with HIV prevalence worldwide. More research is needed to understand
      the circumstances in which IPV and HIV are and are not associated with one
      another.

PMID- 21170390
TI  - Redrawing the map of Great Britain from a network of human interactions.
AB  - Do regional boundaries defined by governments respect the more natural ways that
      people interact across space? This paper proposes a novel, fine-grained approach
      to regional delineation, based on analyzing networks of billions of individual
      human transactions. Given a geographical area and some measure of the strength of
      links between its inhabitants, we show how to partition the area into smaller,
      non-overlapping regions while minimizing the disruption to each person's links.
      We tested our method on the largest non-Internet human network, inferred from a
      large telecommunications database in Great Britain. Our partitioning algorithm
      yields geographically cohesive regions that correspond remarkably well with
      administrative regions, while unveiling unexpected spatial structures that had
      previously only been hypothesized in the literature. We also quantify the effects
      of partitioning, showing for instance that the effects of a possible secession of
      Wales from Great Britain would be twice as disruptive for the human network than
      that of Scotland.

PMID- 21170391
TI  - Defect Characterization in SiGe/SOI Epitaxial Semiconductors by Positron
      Annihilation.
AB  - The potential of positron annihilation spectroscopy (PAS) for defect
      characterization at the atomic scale in semiconductors has been demonstrated in
      thin multilayer structures of SiGe (50 nm) grown on UTB (ultra-thin body) SOI
      (silicon-on-insulator). A slow positron beam was used to probe the defect
      profile. The SiO(2)/Si interface in the UTB-SOI was well characterized, and a
      good estimation of its depth has been obtained. The chemical analysis indicates
      that the interface does not contain defects, but only strongly localized charged
      centers. In order to promote the relaxation, the samples have been submitted to a
      post-growth annealing treatment in vacuum. After this treatment, it was possible
      to observe the modifications of the defect structure of the relaxed film.
      Chemical analysis of the SiGe layers suggests a prevalent trapping site
      surrounded by germanium atoms, presumably Si vacancies associated with misfit
      dislocations and threading dislocations in the SiGe films. 

PMID- 21170392
TI  - Eighth International Workshop on Epitaxial Semiconductors on Patterned Substrates
      and Novel Index Surfaces.

PMID- 21170393
TI  - Is it adaptive to disengage from demands of social change? Adjustment to
      developmental barriers in opportunity-deprived regions.
AB  - This paper investigates how individuals deal with demands of social and economic
      change in the domains of work and family when opportunities for their mastery are
      unfavorable. Theoretical considerations and empirical research suggest that with
      unattainable goals and unmanageable demands motivational disengagement and self
      protective cognitions bring about superior outcomes than continued goal striving.
      Building on research on developmental deadlines, this paper introduces the
      concept of developmental barriers to address socioeconomic conditions of severely
      constrained opportunities in certain geographical regions. Mixed-effects methods
      were used to model cross-level interactions between individual-level compensatory
      secondary control and regional-level opportunity structures in terms of social
      indicators for the economic prosperity and family friendliness. Results showed
      that disengagement was positively associated with general life satisfaction in
      regions that were economically devastated and has less than average services for
      families. In regions that were economically well off and family-friendly, the
      association was negative. Similar results were found for self-protection
      concerning domain-specific satisfaction with life. These findings suggest that
      compensatory secondary control can be an adaptive way of mastering a demand when
      primary control is not possible.

PMID- 21170394
TI  - Micropatterning of Aptamer Beacons to Create Cytokine-Sensing Surfaces.
AB  - Aptamer beacons are DNA or RNA probes that bind proteins or small molecules of
      interest and emit signal directly upon interaction with the target analyte. This
      paper describes micropatterning of aptamer beacons for detection of IFN-gamma-an
      important inflammatory cytokine. The beacon consisted of a fluorophore-labeled
      aptamer strand hybridized with a shorter, quencher-carrying complementary strand.
      Cytokine molecules were expected to displace quenching strands of the beacon,
      disrupting FRET effect and resulting in fluorescence signal. The glass substrate
      was first micropatterned with poly(ethylene glycol) (PEG) hydrogel microwells (35
      MUm diameter individual wells) so as to define sites for attachment of beacon
      molecules. PEG microwell arrays were then incubated with avidin followed by
      biotin-aptamer-fluorophore constructs. Subsequent incubation with quencher
      carrying complementary strands resulted in formation of DNA duplex and caused
      quenching of fluorescence due to FRET effect. When exposed to IFN-gamma,
      microwells changed fluorescence from low (quencher hybridized with fluorophore
      carrying strand) to high (quenching strand displaced by cytokine molecules). The
      fluorescence signal was confined to microwells, was changing in real-time and was
      dependent on the concentration of IFN-gamma. In the future, we plan to co
      localize aptamer beacons and cells on micropatterned surfaces in order to monitor
      in real-time cytokine secretion from immune cells in microwells.

PMID- 21170395
TI  - A Critical New Pathway Towards Change in Abusive Relationships: The Theory of
      Transition Framework.
AB  - This article explores the use of "Transition Framework" as a conceptual framework
      for individual and social change. William Bridges introduced Transition Framework
      in the 1970s as a three-pronged model explaining how people respond to change in
      their lives. This article argues that such an approach has the potential to help
      clients recognize and grieve the loss of their old identities, become comfortable
      with new ways of communicating, understand their cycles of relapse and make
      positive changes. The relevance of this model to transformative change in
      domestic violence treatment is explored.

PMID- 21170396
TI  - Growth of Low-Density Vertical Quantum Dot Molecules with Control in Energy
      Emission.
AB  - In this work, we present results on the formation of vertical molecule structures
      formed by two vertically aligned InAs quantum dots (QD) in which a deliberate
      control of energy emission is achieved. The emission energy of the first layer of
      QD forming the molecule can be tuned by the deposition of controlled amounts of
      InAs at a nanohole template formed by GaAs droplet epitaxy. The QD of the second
      layer are formed directly on top of the buried ones by a strain-driven process.
      In this way, either symmetric or asymmetric vertically coupled structures can be
      obtained. As a characteristic when using a droplet epitaxy patterning process,
      the density of quantum dot molecules finally obtained is low enough (2 * 10(8)
      cm(-2)) to permit their integration as active elements in advanced photonic
      devices where spectroscopic studies at the single nanostructure level are
      required. 

PMID- 21170397
TI  - Ordered Arrays of SiGe Islands from Low-Energy PECVD.
AB  - SiGe islands have been proposed for applications in the fields of
      microelectronics, optoelectronics and thermoelectrics. Although most of the works
      in literature are based on MBE, one of the possible advantages of low-energy
      plasma-enhanced chemical vapor deposition (LEPECVD) is a wider range of
      deposition rates, which in turn results in the possibility of growing islands
      with a high Ge concentration. We will show that LEPECVD can be effectively used
      for the controlled growth of ordered arrays of SiGe islands. In order to control
      the nucleation of the islands, patterned Si (001) substrates were obtained by e
      beam lithography (EBL) and dry etching. We realized periodic circular pits with
      diameters ranging from 80 to 300 nm and depths from 65 to 75 nm. Subsequently,
      thin films (0.8-3.2 nm) of pure Ge were deposited by LEPECVD, resulting in
      regular and uniform arrays of Ge-rich islands. LEPECVD allowed the use of a wide
      range of growth rates (0.01-0.1 nm s(-1)) and substrates temperatures (600-750
      degrees C), so that the Ge content of the islands could be varied. Island
      morphology was characterized by AFM, while MU-Raman was used to analyze the Ge
      content inside the islands and the composition differences between islands on
      patterned and unpatterned areas of the substrate. 

PMID- 21170398
TI  - Size Evolution of Ordered SiGe Islands Grown by Surface Thermal Diffusion on Pit
      Patterned Si(100) Surface.
AB  - The ordered growth of self-assembled SiGe islands by surface thermal diffusion in
      ultra high vacuum from a lithographically etched Ge stripe on pit-patterned
      Si(100) surface has been experimentally investigated. The total surface coverage
      of Ge strongly depends on the distance from the source stripe, as quantitatively
      verified by Scanning Auger Microscopy. The size distribution of the islands as a
      function of the Ge coverage has been studied by coupling atomic force microscopy
      scans with Auger spectro-microscopy data. Our observations are consistent with a
      physical scenario where island positioning is essentially driven by energetic
      factors, which predominate with respect to the local kinetics of diffusion, and
      the growth evolution mainly depends on the local density of Ge atoms.

PMID- 21170399
TI  - Ovaries of Tubificinae (Clitellata, Naididae) resemble ovary cords found in
      Hirudinea (Clitellata).
AB  - The ultrastructure of the ovaries and oogenesis was studied in three species of
      three genera of Tubificinae. The paired ovaries are small, conically shaped
      structures, connected to the intersegmental septum between segments X and XI by
      their narrow end. The ovaries are composed of syncytial cysts of germ cells
      interconnected by stable cytoplasmic bridges (ring canals) and surrounded by
      follicular cells. The architecture of the germ-line cysts is exactly the same as
      in all clitellate annelids studied to date, i.e. each cell in a cyst has only one
      ring canal connecting it to the central, anuclear cytoplasmic mass, the
      cytophore. The ovaries found in all of the species studied seem to be meroistic,
      i.e. the ultimate fate of germ cells within a cyst is different, and the majority
      of cells withdraw from meiosis and become nurse cells; the rest continue meiosis,
      gather macromolecules, cell organelles and storage material, and become oocytes.
      The ovaries are polarized; their narrow end contains mitotically dividing oogonia
      and germ cells entering the meiosis prophase; whereas within the middle and basal
      parts, nurse cells, a prominent cytophore and growing oocytes occur. During late
      previtellogenesis/early vitellogenesis, the oocytes detach from the cytophore and
      float in the coelom; they are usually enveloped by the peritoneal epithelium and
      associated with blood vessels. Generally, the organization of ovaries in all of
      the Tubificinae species studied resembles the polarized ovary cords found within
      the ovisacs of some Euhirudinea. The organization of ovaries and the course of
      oogenesis between the genera studied and other clitellate annelids are compared.
      Finally, it is suggested that germ-line cysts formation and the meroistic mode of
      oogenesis may be a primary character for all Clitellata.

PMID- 21170400
TI  - Self-Assembled Local Artificial Substrates of GaAs on Si Substrate.
AB  - We propose a self-assembling procedure for the fabrication of GaAs islands by
      Droplet Epitaxy on silicon substrate. Controlling substrate temperature and
      amount of supplied gallium is possible to tune the base size of the islands from
      70 up to 250 nm and the density from 10(7) to 10(9) cm(-2). The islands show a
      standard deviation of base size distribution below 10% and their shape evolves
      changing the aspect ratio from 0.3 to 0.5 as size increases. Due to their
      characteristics, these islands are suitable to be used as local artificial
      substrates for the integration of III-V quantum nanostructures directly on
      silicon substrate. 

PMID- 21170401
TI  - Lateral Ordering of InAs Quantum Dots on Cross-hatch Patterned GaInP.
AB  - We report the use of partially relaxed tensile as well as compressively strained
      GaInP layers for lateral ordering of InAs quantum dots with the aid of misfit
      dislocation networks. The strained layers and the InAs QDs were characterized by
      means of atomic force microscopy, scanning electron microscopy, and X-ray
      reciprocal space mapping. The QD-ordering properties of compressive GaInP are
      found to be very similar with respect to the use of compressive GaInAs, while a
      significantly stronger ordering of QDs was observed on tensile GaInP.
      Furthermore, we observed a change of the major type of dislocation in GaInP
      layers as the growth temperature was modified. 

PMID- 21170402
TI  - Single InGaAs Quantum Dot Coupling to the Plasmon Resonance of a Metal
      Nanocrystal.
AB  - We report the observation of coupling of single InGaAs quantum dots with the
      surface plasmon resonance of a metal nanocrystal, which leads to clear
      enhancement of the photoluminescence in the spectral region of the surface
      plasmon resonance of the metal structures. Sharp emission lines, typical for
      single quantum dot emission, are observed, whereas for reference samples, only
      weak continuous background emission is visible. The composite metal-semiconductor
      structure is prepared by molecular beam epitaxy utilizing the principle of strain
      driven adatom migration for the positioning of the metal nanocrystals with
      respect to the quantum dots without use of any additional processing steps. 

PMID- 21170403
TI  - Surface Chemistry Involved in Epitaxy of Graphene on 3C-SiC(111)/Si(111).
AB  - Surface chemistry involved in the epitaxy of graphene by sublimating Si atoms
      from the surface of epitaxial 3C-SiC(111) thin films on Si(111) has been studied.
      The change in the surface composition during graphene epitaxy is monitored by in
      situ temperature-programmed desorption spectroscopy using deuterium as a probe
      (D(2)-TPD) and complementarily by ex situ Raman and C1s core-level
      spectroscopies. The surface of the 3C-SiC(111)/Si(111) is Si-terminated before
      the graphitization, and it becomes C-terminated via the formation of C-rich (6?3
      * 6?3)R30 degrees  reconstruction as the graphitization proceeds, in a similar
      manner as the epitaxy of graphene on Si-terminated 6H-SiC(0001) proceeds. 

PMID- 21170404
TI  - Deep-level Transient Spectroscopy of GaAs/AlGaAs Multi-Quantum Wells Grown on
      (100) and (311)B GaAs Substrates.
AB  - Si-doped GaAs/AlGaAs multi-quantum wells structures grown by molecular beam
      epitaxy on (100) and (311)B GaAs substrates have been studied by using
      conventional deep-level transient spectroscopy (DLTS) and high-resolution Laplace
      DLTS techniques. One dominant electron-emitting level is observed in the quantum
      wells structure grown on (100) plane whose activation energy varies from 0.47 to
      1.3 eV as junction electric field varies from zero field (edge of the depletion
      region) to 4.7 * 10(6) V/m. Two defect states with activation energies of 0.24
      and 0.80 eV are detected in the structures grown on (311)B plane. The E(c)-0.24
      eV trap shows that its capture cross-section is strongly temperature dependent,
      whilst the other two traps show no such dependence. The value of the capture
      barrier energy of the trap at E(c)-0.24 eV is 0.39 eV. 

PMID- 21170405
TI  - Surface Modification and Planar Defects of Calcium Carbonates by Magnetic Water
      Treatment.
AB  - Powdery calcium carbonates, predominantly calcite and aragonite, with planar
      defects and cation-anion mixed surfaces as deposited on low-carbon steel by
      magnetic water treatment (MWT) were characterized by X-ray diffraction, electron
      microscopy, and vibration spectroscopy. Calcite were found to form faceted
      nanoparticles having 3x (0114) commensurate superstructure and with well
      developed {1120} and {1014} surfaces to exhibit preferred orientations. Aragonite
      occurred as laths having 3x (011) commensurate superstructure and with well
      developed (011) surface extending along [100] direction up to micrometers in
      length. The (hkil)-specific coalescence of calcite and rapid lath growth of
      aragonite under the combined effects of Lorentz force and a precondensation event
      account for a beneficial larger particulate/colony size for the removal of the
      carbonate scale from the steel substrate. The coexisting magnetite particles have
      well-developed {011} surfaces regardless of MWT. 

PMID- 21170406
TI  - Porous Alumina Films with Width-Controllable Alumina Stripes.
AB  - Porous alumina films had been fabricated by anodizing from aluminum films after
      an electropolishing procedure. Alumina stripes without pores can be distinguished
      on the surface of the porous alumina films. The width of the alumina stripes
      increases proportionally with the anodizing voltage. And the pores tend to be
      initiated close to the alumina stripes. These phenomena can be ascribed to the
      electric field distribution in the alumina barrier layer caused by the geometric
      structure of the aluminum surface. 

PMID- 21170407
TI  - Excitation Intensity Driven PL Shifts of SiGe Islands on Patterned and Planar
      Si(001) Substrates: Evidence for Ge-rich Dots in Islands.
AB  - For randomly nucleated SiGe/Si(001) islands, a significantly stronger blue-shift
      of the PL spectra as a function of the excitation intensity is observed when
      compared to islands grown on patterned substrates side by side within the same
      run in a solid source molecular beam epitaxy chamber. We ascribe this different
      PL behavior to the much larger inhomogeneity of the Ge distribution in islands on
      planar substrates when compared to islands grown on pit-patterned ones, as
      observed previously. 3D band-structure calculations show that Ge-rich inclusions
      of approximately 5 nm diameter at the apex of the islands can account for the
      observed differences in the PL spectra. The existence of such inclusions can be
      regarded as a quantum dot in an island and is in agreement with recent nano
      tomography experiments. 

PMID- 21170408
TI  - Highly Efficient Near-IR Photoluminescence of Er Immobilized in Mesoporous SBA
      15.
AB  - SiO(2) mesoporous molecular sieve SBA-15 with the incorporation of erbium ions is
      studied as a novel type of nanoscopic composite photoluminescent material in this
      paper. To enhance the photoluminescence efficiency, two schemes have been used
      for the incorporation of Er(3+) where (1) Er(3+) is ligated with bis
      (perfluoromethylsulfonyl)-aminate (PMS) forming Er(PMS)(x)-SBA-15 and (2) Yb(3+)
      is codoped with Er(3+) forming Yb-Er-SBA-15. As high as 11.17 * 10(-21)cm(2) of
      fluorescent cross section at 1534 nm and 88 nm of "effective bandwidth" have been
      gained. It is a 29.3% boost in fluorescent cross section compared to what has
      been obtained in conventional silica. The upconversion coefficient in Yb-Er-SBA
      15 is relatively small compared to that in other ordinary glass hosts. The
      increased fluorescent cross section and lowered upconversion coefficient could
      benefit for the high-gain optical amplifier. Finally, the Judd-Ofelt theory has
      also been used for the analyses of the optical spectra of Er(PMS)(x)-SBA-15. 

PMID- 21170409
TI  - Hydrothermal Synthesis, Microstructure and Photoluminescence of Eu-Doped Mixed
      Rare Earth Nano-Orthophosphates.
AB  - Eu(3+)-doped mixed rare earth orthophosphates (rare earth = La, Y, Gd) have been
      prepared by hydrothermal technology, whose crystal phase and microstructure both
      vary with the molar ratio of the mixed rare earth ions. For La(x)Y(1-x)PO(4):
      Eu(3+), the ion radius distinction between the La(3+) and Y(3+) is so large that
      only La(0.9)Y(0.1)PO(4): Eu(3+) shows the pure monoclinic phase. For La(x)Gd(1
      x)PO(4): Eu(3+) system, with the increase in the La content, the crystal phase
      structure of the product changes from the hexagonal phase to the monoclinic phase
      and the microstructure of them changes from the nanorods to nanowires. Similarly,
      Y(x)Gd(1-x)PO(4): Eu(3+), Y(0.1)Gd(0.9)PO(4): Eu(3+) and Y(0.5)Gd(0.5)PO(4):
      Eu(3+) samples present the pure hexagonal phase and nanorods microstructure,
      while Y(0.9)Gd(0.1)PO(4): Eu(3+) exhibits the tetragonal phase and nanocubic
      micromorphology. The photoluminescence behaviors of Eu(3+) in these hosts are
      strongly related to the nature of the host (composition, crystal phase and
      microstructure). 

PMID- 21170410
TI  - Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI
      Contrast Agents.
AB  - Biocompatible poly-[N-(2-hydroxyethyl)-d,l-aspartamide]
      methoxypoly(ethyleneglycol)-hexadecylamine (PHEA-mPEG-C(16)) conjugated with
      1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd) via
      ethylenediamine (ED) was synthesized as a magnetic resonance imaging (MRI)
      contrast agent. Amphiphilic PHEA-mPEG-C(16)-ED-DOTA-Gd forms micelle in aqueous
      solution. All the synthesized materials were characterized by proton nuclear
      magnetic resonance ((1)H NMR). Micelle size and shape were examined by dynamic
      light scattering (DLS) and atomic force microscopy (AFM). Micelles with PHEA-mPEG
      C(16)-ED-DOTA-Gd showed higher relaxivities than the commercially available
      gadolinium contrast agent. Moreover, the signal intensity of a rabbit liver was
      effectively increased after intravenous injection of PHEA-mPEG-C(16)-ED-DOTA-Gd. 

PMID- 21170411
TI  - Optimization of an Electron Transport Layer to Enhance the Power Conversion
      Efficiency of Flexible Inverted Organic Solar Cells.
AB  - The photovoltaic (PV) performance of flexible inverted organic solar cells
      (IOSCs) with an active layer consisting of a blend of poly(3-hexylthiophene) and
      [6, 6]-phenyl C(61)-butlyric acid methyl ester was investigated by varying the
      thicknesses of ZnO seed layers and introducing ZnO nanorods (NRs). A ZnO seed
      layer or ZnO NRs grown on the seed layer were used as an electron transport layer
      and pathway to optimize PV performance. ZnO seed layers were deposited using spin
      coating at 3,000 rpm for 30 s onto indium tin oxide (ITO)-coated
      polyethersulphone (PES) substrates. The ZnO NRs were grown using an aqueous
      solution method at a low temperature (90 degrees C). The optimized device with
      ZnO NRs exhibited a threefold increase in PV performance compared with that of a
      device consisting of a ZnO seed layer without ZnO NRs. Flexible IOSCs fabricated
      using ZnO NRs with improved PV performance may pave the way for the development
      of PV devices with larger interface areas for effective exciton dissociation and
      continuous carrier transport paths. 

PMID- 21170412
TI  - Statistical Analysis of Surface Reconstruction Domains on InAs Wetting Layer
      Preceding Quantum Dot Formation.
AB  - Surface of an InAs wetting layer on GaAs(001) preceding InAs quantum dot (QD)
      formation was observed at 300 degrees C with in situ scanning tunneling
      microscopy (STM). Domains of (1 * 3)/(2 * 3) and (2 * 4) surface reconstructions
      were located in the STM image. The density of each surface reconstruction domain
      was comparable to that of subsequently nucleated QD precursors. The distribution
      of the domains was statistically investigated in terms of spatial point patterns.
      It was found that the domains were distributed in an ordered pattern rather than
      a random pattern. It implied the possibility that QD nucleation sites are related
      to the surface reconstruction domains. 

PMID- 21170413
TI  - Optimal Growth Conditions for Selective Ge Islands Positioning on Pit-Patterned
      Si(001).
AB  - We investigate ordered nucleation of Ge islands on pit-patterned Si(001) using an
      original hybrid Kinetic Monte Carlo model. The method allows us to explore long
      time-scale evolution while using large simulation cells. We analyze the
      possibility to achieve selective nucleation and island homogeneity as a function
      of the various parameters (flux, temperature, pit period) able to influence the
      growth process. The presence of an optimal condition where the atomic diffusivity
      is sufficient to guarantee nucleation only within pits, but not so large to
      induce significant Ostwald ripening, is clearly demonstrated. 

PMID- 21170414
TI  - Growth Interruption Effect on the Fabrication of GaAs Concentric Multiple Rings
      by Droplet Epitaxy.
AB  - WE PRESENT THE MOLECULAR BEAM EPITAXY FABRICATION AND OPTICAL PROPERTIES OF
      COMPLEX GAAS NANOSTRUCTURES BY DROPLET EPITAXY: concentric triple quantum rings.
      A significant difference was found between the volumes of the original droplets
      and the final GaAs structures. By means of atomic force microscopy and
      photoluminescence spectroscopy, we found that a thin GaAs quantum well-like layer
      is developed all over the substrate during the growth interruption times, caused
      by the migration of Ga in a low As background. 

PMID- 21170415
TI  - Finding related sentence pairs in MEDLINE.
AB  - We explore the feasibility of automatically identifying sentences in different
      MEDLINE abstracts that are related in meaning. We compared traditional vector
      space models with machine learning methods for detecting relatedness, and found
      that machine learning was superior. The Huber method, a variant of Support Vector
      Machines which minimizes the modified Huber loss function, achieves 73% precision
      when the score cutoff is set high enough to identify about one related sentence
      per abstract on average. We illustrate how an abstract viewed in PubMed might be
      modified to present the related sentences found in other abstracts by this
      automatic procedure.

PMID- 21170417
TI  - Differential diagnosis of thyroid nodules using fine-needle aspiration cytology
      and oncogene mutation screening: are we ready?
AB  - Thyroid nodules are a very common clinical finding, and although the majority of
      them are benign, thyroid carcinoma accounts for about 5-15% of nodules. Fine
      needle aspiration cytology (FNAC) is actually used for the differential diagnosis
      of these lesions. Although in most cases this examination clearly distinguishes
      benign from malignant lesions, some fine-needle aspiration (FNA) samples fall
      into undetermined thyroid cytology categories, which according to the most recent
      classification of thyroid FNAC consist of 'suspicious for malignancy',
      'suspicious for follicular or Hurtle cell neoplasm', and 'follicular lesion of
      undetermined significance/atypia of undetermined significance'. Moreover, some
      samples are insufficient for diagnosis. Taken together, these categories account
      for almost 20-30% of nodules. Owing to the high risk of papillary thyroid
      carcinoma, patients with lesions that are 'suspicious for malignancy' are
      currently subjected to lobectomy or total thyroidectomy. On the other hand,
      patients with 'atypia of undetermined significance' undergo repeated FNAs, and
      patients with 'suspicious for follicular or Hurtle cell neoplasm' are subjected
      to diagnostic lobectomy and subsequently, in the case of histological diagnosis
      of carcinoma, total thyroidectomy. Recent studies clearly indicate that molecular
      analysis of thyroid nodules can significantly improve the diagnostic power of
      cytology and drive the appropriate clinical management of these patients.

PMID- 21170418
TI  - A Comparative Analysis of Competency Frameworks for Youth Workers in the Out-of
      School Time Field.
AB  - Research suggests that the quality of out-of-school time (OST) programs is
      related to positive youth outcomes and skilled staff are a critical component of
      high quality programming. This descriptive case study of competency frameworks
      for youth workers in the OST field demonstrates how experts and practitioners
      characterize a skilled youth worker. A comparative analysis of 11 competency
      frameworks is conducted to identify a set of common core competencies. A set of
      12 competency areas that are shared by existing frameworks used in the OST field
      are identified. The age of youth being served, descriptions of mastery for each
      competency area, an emphasis on developing mid-level managers, and incorporating
      research emerge as factors that should be addressed in future competency
      frameworks.

PMID- 21170416
TI  - Pyrvinium, a potent small molecule Wnt inhibitor, promotes wound repair and post
      MI cardiac remodeling.
AB  - Wnt signaling plays an important role in developmental and stem cell biology. To
      test the hypothesis that temporary inhibition of Wnt signaling will enhance
      granulation tissue and promote angiogenesis in tissue repair, we employed a
      recently characterized small molecule Wnt inhibitor. Pyrvinium is an FDA-approved
      drug that we identified as a Wnt inhibitor in a chemical screen for small
      molecules that stabilize beta-catenin and inhibit Axin degradation. Our
      subsequent characterization of pyrvinium has revealed that its critical cellular
      target in the Wnt pathway is Casein Kinase 1alpha. Daily administration of
      pyrvinium directly into polyvinyl alcohol (PVA) sponges implanted subcutaneously
      in mice generated better organized and vascularized granulation tissue; this
      compound also increased the proliferative index of the tissue within the sponges.
      To evaluate its effect in myocardial repair, we induced a myocardial infarction
      (MI) by coronary artery ligation and administered a single intramyocardial dose
      of pyrvinium. Mice were evaluated by echocardiography at 7 and 30 days post-MI
      and treatment; post mortem hearts were evaluated by histology at 30 days.
      Pyrvinium reduced adverse cardiac remodeling demonstrated by decreased left
      ventricular internal diameter in diastole (LVIDD) as compared to a control
      compound. Increased Ki-67+ cells were observed in peri-infarct and distal
      myocardium of pyrvinium-treated animals. These results need to be further
      followed-up to determine if therapeutic inhibition of canonical Wnt may avert
      adverse remodeling after ischemic injury and its impact on myocardial repair and
      regeneration.

PMID- 21170419
TI  - Clinician and Parent Perspectives on Parent and Family Contextual Factors that
      Impact Community Mental Health Services for Children with Behavior Problems.
AB  - The present study employed qualitative methods to examine multiple stakeholder
      perspectives regarding the role of parent and family contextual factors on
      community child mental health treatment for children with behavior problems.
      Findings suggest agreement between clinicians and parents on the number, types
      and importance of parent and family factors in children's mental health services;
      however, stakeholders differed in reports of which factors were most salient.
      Specifically, clinicians endorsed most factors as being equally salient, while
      parents described a few salient factors, with parental stress and inadequate
      social support being the most frequently discussed. These qualitative data
      further elucidate the context of community services and have implications for
      evidence-based practice implementation and improving community care.

PMID- 21170420
TI  - Concentric Multiple Rings by Droplet Epitaxy: Fabrication and Study of the
      Morphological Anisotropy.
AB  - We present the Molecular Beam Epitaxy fabrication of complex GaAs/AlGaAs
      nanostructures by Droplet Epitaxy, characterized by the presence of concentric
      multiple rings. We propose an innovative experimental procedure that allows the
      fabrication of individual portions of the structure, controlling their diameter
      by only changing the substrate temperature. The obtained nanocrystals show a
      significant anisotropy between [110] and [1-10] crystallographic directions,
      which can be ascribed to different activation energies for the Ga atoms migration
      processes. 

PMID- 21170421
TI  - Metabolic control analysis of integrated energy metabolism in permeabilized
      cardiomyocytes - experimental study.
AB  - The main focus of this research was to apply Metabolic Control Analysis to
      quantitative investigation of the regulation of respiration by components of the
      Mitochondrial Interactosome (MI, a supercomplex consisting of ATP Synthasome,
      mitochondrial creatine kinase (MtCK), voltage dependent anion channel (VDAC), and
      tubulin) in permeabilized cardiomyocytes. Flux control coefficients (FCC) were
      measured using two protocols: 1) with direct ADP activation, and 2) with MtCK
      activation by creatine (Cr) in the presence of ATP and pyruvate kinase
      phosphoenolpyruvate system. The results show that the metabolic control is much
      stronger in the latter case: the sum of the measured FCC is 2.7 versus 0.74 (ADP
      activation). This is consistent with previous data showing recycling of ADP and
      ATP inside the MI due to the functional coupling between MtCK and ANT and limited
      permeability of VDAC for these compounds, PCr being the major energy carrier
      between the mitochondria and ATPases. In physiological conditions, when the MI is
      activated, the key sites of regulation of respiration in mitochondria are MtCK
      (FCC = 0.93), adenine nucleotide translocase ANT (FCC = 0.95) and CoQ cytochrome
      c oxidoreductase (FCC = 0.4). These results show clearly that under the
      physiological conditions the energy transfer from mitochondria to the cytoplasm
      is regulated by the MI supercomplex and is very sensitive to metabolic signals.

PMID- 21170422
TI  - The influence of the potassium promoter on the kinetics and thermodynamics of CO
      adsorption on a bulk iron catalyst applied in Fischer-Tropsch synthesis: a
      quantitative adsorption calorimetry, temperature-programmed desorption, and
      surface hydrogenation study.
AB  - The adsorption of carbon monoxide on an either unpromoted or potassium-promoted
      bulk iron catalyst was investigated at 303 K and 613 K by means of pulse
      chemisorption, adsorption calorimetry, temperature-programmed desorption and
      temperature-programmed surface reaction in hydrogen. CO was found to adsorb
      mainly molecularly in the absence of H(2) at 303 K, whereas the presence of H(2)
      induced CO dissociation at higher temperatures leading to the formation of CH(4)
      and H(2)O. The hydrogenation of atomic oxygen chemisorbed on metallic iron was
      found to occur faster than the hydrogenation of atomically adsorbed carbon. At
      613 K CO adsorption occurred only dissociatively followed by recombinative CO(2)
      formation according to C(ads) + 2O(ads)-> CO(2(g)). The presence of the potassium
      promoter on the catalyst surface led to an increasing strength of the Fe-C bond
      both at 303 K and 613 K: the initial differential heat of molecular CO adsorption
      on the pure iron catalyst at 303 K amounted to 102 kJ mol(-1), whereas it
      increased to 110 kJ mol(-1) on the potassium-promoted sample, and the initial
      differential heat of dissociative CO adsorption on the unpromoted iron catalyst
      at 613 K amounted to 165 kJ mol(-1), which increased to 225 kJ mol(-1) in the
      presence of potassium. The calorimetric CO adsorption experiments also reveal a
      change of the energetic distribution of the CO adsorption sites present on the
      catalyst surface induced by the potassium promoter, which was found to block a
      fraction of the CO adsorption sites.

PMID- 21170423
TI  - Synthesis and crystal structure of a rare square-planar Co(II) complex of a
      hydroxyamidinate ligand.
AB  - Novel hydroxyamidinate complexes of cobalt(II) are presented, together with their
      electrochemical and spectroscopic properties. An unusual d(7) square-planar
      coordination around the cobalt(II) center exists and was confirmed by chemical
      oxidation to its Co(III) species. The Co(II) complex is difficult to reduce, but
      its facile oxidation suggests that it may be useful as an electron donor in
      photoredox reactions.

PMID- 21170425
TI  - Seed-mediated growth of palladium nanocrystals: the effect of pseudo-halide
      thiocyanate ions.
AB  - In synthesis in a solution phase, adsorbates such as halides can interact
      selectively with different metal crystal facets and affect the final morphology
      of nanocrystals. Pseudo-halide thiocyanate ions (SCN-) can also adsorb on the
      metal surface, but they have never been used for the synthesis of shape
      controlled colloidal metal nanocrystals. In this study, we first investigated the
      effect of SCN- on the morphology of palladium nanocrystals through a seed
      mediated growth method. The presence of 1 uM SCN- in the growth solutions could
      lead to the formation of palladium polyhedra: truncated rhombic dodecahedra
      enclosed by twelve {110}, eight {111} and six {100} facets. The products were
      nanocubes enclosed with six {100} facets if cetyltrimethylammonium bromide (CTAB)
      was the only capping agent. Meanwhile, the mechanism of the effect of SCN- on the
      morphology of Pd nanocrystals is discussed.

PMID- 21170426
TI  - Scanned chemical enhancement of surface-enhanced Raman scattering using a charge
      transfer complex.
AB  - We have fabricated a charge-transfer system using the self-assembly method. We
      find the nontotally symmetric b(2) modes are selectively enhanced in SERS
      spectroscopy and represent a laser wavelength-dependent property.

PMID- 21170424
TI  - A sea of biosynthesis: marine natural products meet the molecular age.

PMID- 21170427
TI  - Low-melting zwitterion: effect of oxyethylene units on thermal properties and
      conductivity.
AB  - An imidazolium-based zwitterion containing two oxyethylene units was obtained as
      a colorless liquid at room temperature. The equimolar mixture of the liquid
      zwitterion and lithium bis(trifluoromethylsulfonyl)amide showed an ionic
      conductivity of over 10(-4) S cm(-1) at 80  degrees C, which was higher than
      those of mixtures composed of analogous solid zwitterions.

PMID- 21170428
TI  - Anisotropic oxygen plasma etching of colloidal particles in electrospun fibers.
AB  - Oxygen plasma etching of electrospun polymer fibers containing spherical colloids
      is presented as a new approach towards anisotropic colloidal nanoparticles. The
      detailed morphology of the resulting nanoparticles can be precisely controlled in
      a continuous way. The same approach is also amenable to prepare inorganic
      nanoparticles with double-sided patches.

PMID- 21170429
TI  - Evaluation of polyketones with N-cyclic structure as electrode material for
      electrochemical energy storage: case of pyromellitic diimide dilithium salt.
AB  - Pyromellitic diimide dilithium salt was selected to complete our database on
      redox-active polyketones with a N-cyclic structure. Although never reported to
      date, such a lithiated salt was readily synthesized making its electrochemical
      evaluation in a Li battery possible. Preliminary data show that this novel
      material reversibly inserts two Li per formula unit at a relatively low potential
      giving a stable capacity value of 200 mAh g(-1).

PMID- 21170430
TI  - A new linker for solid-phase synthesis of heparan sulfate precursors by
      sequential assembly of monosaccharide building blocks.
AB  - A novel ester type linker which upon cleavage releases the glycans as carbamate
      protected aminoglycosides was successfully employed in the sequential assembly of
      L-idose and azido glucose monosaccharide building blocks to heparan sulfate
      precursors.

PMID- 21170431
TI  - Molecular spin conversion in solid deuterated methane.
AB  - The spin conversion of methane molecules in pure deuterated methane crystals and
      CD(4)-Kr solid solution for a wide range of concentrations of krypton was
      investigated in the temperature range 1.5-10 K. The experiment was performed by
      use of a steady-state heat flow experimental setup for determination of the
      thermal conductivity, utilized in an unconventional way. The obtained results
      were discussed in the frame of the spin conversion model taking into account
      direct one-phonon processes and indirect librationally-activated processes. It
      was found that the conversion, both for pure and krypton doped crystals, is
      dominated by the one-phonon mechanism. However, the importance of the indirect
      processes increases rapidly with the temperature. The obtained results indicate
      that the krypton admixture does not change the values of energy levels of the
      spin-librational (spin-rotational) spectrum of the crystal. The presence of Kr in
      the structure of CD(4) enhances the intensity of the direct one-phonon spin
      conversion processes and weakens the indirect librationally-activated ones.

PMID- 21170432
TI  - Ammonia IRMS-TPD measurements on Bronsted acidity of proton-formed SAPO-34.
AB  - By utilizing the advantages of a combined method of IRMS-TPD of ammonia and DFT
      calculations, the solid acidity of HSAPO-34 was studied. The number, strength and
      structure of the Bronsted OH were measured experimentally. The quantitative
      measurements and DFT calculations supported the identification of Bronsted OH to
      account for the generation model of the Bronsted OH primarily located in the edge
      of the Si domain (island). The acid strength of SAPO-34 was slightly weaker than
      that of chabazite, a zeolite with the same structure. Thus, some important
      insights were obtained to understand the acid site generation of SAPO-34.

PMID- 21170433
TI  - MgCO3.3H2O and MgO complex nanostructures: controllable biomimetic fabrication
      and physical chemical properties.
AB  - In this paper, we report a method of biomimetic synthesis of MgCO(3).3H(2)O and
      MgO Viburnum opulus-like complex nanostructures with superhydrophobicity and
      adsorption properties. The MgCO(3).3H(2)O complex nanostructures can be obtained
      by changing experimental parameters, including concentrations of reactants
      (dextran and MgCl(2)), molar ratios of reactants, and reaction time. The phase
      structure of as-synthesized samples was characterized by X-ray diffraction (XRD).
      The morphology and structure are studied by scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), and Fourier transform infrared (FT-IR)
      spectroscopy. The MgCO(3).3H(2)O complex nanostructures exhibited
      superhydrophobicity, due to their unique superstructures, and was proved by the
      contact angle (CA) measurement. We also show that a simple calcination of these
      unusually shaped MgCO(3).3H(2)O results in spontaneous formation of MgO complex
      nanostructures while the unique shape can be maintained, and the as-synthesized
      MgO nanostructures show excellent adsorption property. These unique structures
      and properties will open up a wide range of potential applications in material
      and environmental protection.

PMID- 21170434
TI  - The effect of membrane fluidity on FRET parameters: an energy transfer study
      inside small unilamellar vesicle.
AB  - The fluorescence resonance energy transfer (FRET) in a lipid bilayer system
      containing two different donors and one common acceptor at below and above
      transition temperature has been studied and all the FRET parameters are analyzed
      using steady state and time-resolved fluorescence spectroscopy. Using dynamic
      light scattering measurement, we have followed the process of preparation of
      small unilamellar vesicles, and by following the FRET parameters of C-153-Rh6G
      and C-151-Rh6G pairs inside SUVs at 16  degrees C and 33  degrees C (T(m) = 23.9 
      degrees C) we have noticed that there is greater effect of temperature on the
      FRET parameters in case of the C-153-Rh6G pair than that of the C-151-Rh6G pair.
      Finally we have concluded that this difference is due to their different location
      inside the lipid bilayer in which fluidity of the long alkyl chain markedly
      affects the FRET parameters for C-153-Rh6G pair embedded inside a small
      unilamellar vesicle of size 20-50 nm.

PMID- 21170435
TI  - Diimide nanoclusters play hole trapping and electron injection roles in organic
      light-emitting devices.
AB  - We report thermally stable diimide nanoclusters that could potentially replace
      the conventional thick electron transport layer (ETL) in organic light-emitting
      devices (OLEDs). Bis-[1,10]phenanthrolin-5-yl-bicyclo[2.2.2]oct-7-ene-2,3,5,6
      tetracarboxylic diimide (Bphen-BCDI) was synthesized from the corresponding
      dianhydride and amine moieties, and its purified product exhibited a high glass
      transition temperature (232  degrees C) and a wide band gap (3.8 eV). The Bphen
      BCDI subnanolayers deposited on substrates were found to form organic
      nanoclusters, not a conventional layer. The OLED made with a subnanolayer of
      Bphen-BCDI nanoclusters, instead of a conventional ETL, showed greatly improved
      efficiency (about 2-fold) compared with an OLED without the diimide nanoclusters.
      The role of the BPhen-BCDI nanoclusters was assigned to hole trapping and
      electron injection in the present OLED structure.

PMID- 21170436
TI  - New hedgehog/GLI-signaling inhibitors from Adenium obesum.
AB  - The aberrant hedgehog (Hh)/GLI signaling pathway causes the formation and
      progression of a variety of tumors. We recently constructed a cell-based
      screening system to search for Hh/GLI signaling inhibitors from natural
      resources. Using our screening system, Adenium obesum was found to include Hh/GLI
      signaling inhibitors from our tropical plant extract libraries. Bioassay-guided
      fractionation of this plant extract led to the isolation of 17 cardiac glycosides
      (1-17), including 3 new compounds (4, 9, 16). These compounds showed strong
      inhibitory activities, especially the IC(50) of 17 is 0.11 MUM. The inhibition of
      GLI-related protein expression with 3, 9, 11, 15 and 17 was observed in human
      pancreatic cancer cells (PANC1), which express Hh/GLI components aberrantly. The
      expressions of GLI-related proteins PTCH and BCL2 were clearly inhibited. These
      compounds also showed selective cytotoxicity against two cancer cell lines, with
      less effect against normal cells (C3H10T1/2). RT-PCT examinations showed that
      Ptch mRNA expression by 3, 11, 15 and 17 was inhibited.

PMID- 21170437
TI  - Reduced graphene oxide as a catalyst for hydrogenation of nitrobenzene at room
      temperature.
AB  - Reduced graphene oxide was used as a catalyst for reduction of nitrobenzene at
      room temperature. High catalytic activity and stability were exhibited in
      circular experiments. The catalytic procedure was in situ monitored by NMR and N
      phenylhydroxylamine was proved to be the intermediate in this catalytic reaction.

PMID- 21170439
TI  - Impact of concentration self-quenching on the charge generation yield of
      fullerene based donor-bridge-acceptor compounds in the solid state.
AB  - A fullerene based Donor-Bridge-Acceptor (DBA) compound, incorporating a pi
      extended tetrathiafulvalene electron donor, is investigated with respect to its
      photophysics in solution versus solid state. Solid films of neat DBA are compared
      with blend films where the DBA compound is diluted in the inert, low dielectric,
      polymer poly(styrene). It is found that the moderate intermolecular electronic
      coupling and donor-acceptor separation (22 A) in this case leads to the
      generation of more dissociated, intermolecular charges than a mixture of the
      donor and acceptor reference compounds. However, the increased intermolecular
      interactions in the solid state lead to the excited state of the fullerene
      suffering from concentration self-quenching. This is found to severely affect the
      charge generation yield in solid films. The impact of competing intra and
      intermolecular interactions in the solid state upon the film photophysics is
      analysed in terms of a kinetic model which includes both the effects of
      concentration self-quenching and the impact of film composition upon the
      dielectric stabilisation of charge separated states. We conclude that both
      concentration self-quenching and dielectric stabilisation are critical in
      determining the photophysics of the blend films, and discuss strategies based
      upon our observations to enhance the charge photogeneration properties of organic
      films and photovoltaic devices based upon DBA compounds.

PMID- 21170438
TI  - Biopolymers phase separation monitored by a plasmonic sensor.
AB  - We report here a real-time study of interactions induced phase separation between
      beta-lactoglobulin (BLG) and Acacia gum (AG) by analyzing the localized surface
      plasmon resonance of silver nanoparticles. We showed that the binding of BLG to
      AG is accompanied by refractive index changes, in relation with optical
      properties and structural changes of the complexes formed.

PMID- 21170440
TI  - Intracule functional models. V. Recurrence relations for two-electron integrals
      in position and momentum space.
AB  - The approach used by Ahlrichs [Phys. Chem. Chem. Phys., 2006, 8, 3072] to derive
      the Obara-Saika recurrence relation (RR) for two-electron integrals over Gaussian
      basis functions, is used to derive an 18-term RR for six-dimensional integrals in
      phase space and 8-term RRs for three-dimensional integrals in position or
      momentum space. The 18-term RR reduces to a 5-term RR in the special cases of Dot
      and Posmom intracule integrals in Fourier space. We use these RRs to show
      explicitly how to construct Position, Momentum, Omega, Dot and Posmom intracule
      integrals recursively.

PMID- 21170441
TI  - Spectroscopic identification of carbon dioxide clusters: (CO2)6 to (CO2)13.
AB  - In spite of wide interest in CO(2) clusters, only dimers and trimers have
      previously been assigned to specific infrared bands. Here, transitions for
      clusters with 6-13 molecules are identified in the nu(3) region (~2350 cm(-1)).
      Spectra are observed in a supersonic jet (T ~ 2.5 K) using a tunable laser probe,
      and analyzed with the aid of cluster calculations based on a widely-used model
      potential. Vibrational origins show blue-shifts significantly larger than
      predicted by resonant dipole interactions.

PMID- 21170442
TI  - Differential cross sections for H + D2 -> HD(v' = 2, j' = 0,3,6,9) + D at center
      of-mass collision energies of 1.25, 1.61, and 1.97 eV.
AB  - We have measured differential cross sections (DCSs) for the reaction H + D(2) ->
      HD(v' = 2,j' = 0,3,6,9) + D at center-of-mass collision energies E(coll) of 1.25,
      1.61, and 1.97 eV using the photoloc technique. The DCSs show a strong dependence
      on the product rotational quantum number. For the HD(v' = 2,j' = 0) product, the
      DCS is bimodal but becomes oscillatory as the collision energy is increased. For
      the other product states, they are dominated by a single peak, which shifts from
      back to sideward scattering as j' increases, and they are in general less
      sensitive to changes in the collision energy. The experimental results are
      compared to quantum mechanical calculations and show good, but not fully
      quantitative agreement.

PMID- 21170443
TI  - Novel single-source precursors for the fabrication of PbTiO3, PbZrO3 and Pb(Zr(1
      x)Ti(x))O3 thin-films by chemical vapor deposition.
AB  - Lead titanate, lead zirconate, and lead zirconate titanate (PZT) films in the sub
      MUm-range were produced at temperatures around 400  degrees C using novel single
      source precursors in a classical thermal CVD process. The design of two
      bimetallic alkoxide compounds, a lead titanate and a lead zirconate source with
      almost identical physical properties and complement miscibility, resulted in a
      new quasi-single-source PZT precursor, an azeotropic mixture that evaporates at
      30  degrees C and at a pressure of 4 * 10(-1) mbar. After thermal treatment at
      650  degrees C, transparent (100)-oriented PZT films with remnant polarization of
      20 MUC cm(-2) and a coercive field strength of 20 V MUm(-1) were achieved. An
      additional lead source is not required.

PMID- 21170444
TI  - Investigation of noble metal nanoparticle zeta-potential effects on single-cell
      exocytosis function in vitro with carbon-fiber microelectrode amperometry.
AB  - Since noble metal nanoparticles are increasingly found in consumer goods, there
      is a need for information about potential impacts of these nanoparticles on
      cellular function to avoid environmental and health risks associated with
      exposure. In this study, spherical Au and Ag nanoparticles of similar size were
      synthesized and modified to assess the effects of zeta-potential on immune cell
      function. Nanoparticle zeta-potential was controlled by employing surfactant
      exchange to generate nanoparticles with positive or negative surface charge.
      Mouse peritoneal mast cells (MPMCs) were then exposed to 5-15 ug ml(-1) of these
      nanomaterials, and uptake was assessed by inductively coupled plasma-atomic
      emission spectroscopy (ICP-AES). Uptake for positively charged nanoparticles was
      more efficient than for negatively charged nanomaterials, and all nanoparticles
      were taken up in a concentration-dependent manner. Following uptake, MPMC
      degranulation function was assessed using carbon-fiber microelectrode amperometry
      (CFMA), showing decreased quantal secretion of serotonin by MPMCs exposed to the
      positively charged Au nanoparticles and negatively charged Ag nanoparticles. The
      overall efficiency of the degranulation process (indicated by amperometric spike
      frequency) decreased for all Au-exposed MPMCs. However, only the negatively
      charged version of the Ag nanomaterial resulted in decreased MPMC degranulation
      efficiency. Further studies revealed that ionic Ag was partially responsible for
      the observed effects. Overall, these studies reveal the complex nature of
      interactions between noble metal nanomaterials and cells that result in perturbed
      cellular function and illustrate the necessity of thorough nanoparticle
      characterization for interpretation of cellular function assays.

PMID- 21170445
TI  - Luminescent lanthanide complexes as analytical tools in anion sensing, pH
      indication and protein recognition.
AB  - Although lanthanide complexes are recently used in luminescence labeling of bio
      targets, this review focuses on sensing profiles of synthetic and biological
      lanthanide complexes. Rational design and combinatorial screening approaches
      toward synthetic lanthanide complexes applicable as luminescent sensing materials
      are described. Iron-carrying transferrin and ferritin proteins further form
      lanthanide complexes working as pH indicators and protein recognition reagents.

PMID- 21170446
TI  - Electrochemical detection of extracellular hydrogen peroxide released from RAW
      264.7 murine macrophage cells based on horseradish peroxidase-hydroxyapatite
      nanohybrids.
AB  - A new method developed for the reliable determination of extracellular and
      intracellular H(2)O(2) is very useful for gaining a full understanding of the
      role that H(2)O(2) plays in pathology and physiology, and the relationship
      between H(2)O(2) and environmental stresses and lipid peroxidation. This work
      developed and validated an electrochemical approach for the determination of
      extracellular H(2)O(2) released from RAW 264.7 murine macrophage cells. This
      approach is based on the electrocatalytic reduction of the released H(2)O(2) at
      the biosensor of HRP-HAP/GC, which was fabricated by depositing the horseradish
      peroxidase-hydroxyapatite (HRP-HAP) nanohybrids on a glassy carbon (GC, 3 mm in
      diameter) electrode. The biosensor exhibited a rapid response (less than 2 s), a
      low detection limit (0.1+/-0.02 MUM), a wide linear range (5 MUM to 0.82 mM), as
      well as good stability and repeatability. In addition, the common interfering
      species, such as uric acid (UA), ascorbic acid (AA), glucose, and 3,4
      dihydroxyphenylacetic acid (DOPAC), etc., did not cause any interference due to
      the use of a low operating potential (-400 mV, versus SCE). Therefore, this work
      has demonstrated a simple and effective sensing platform for the detection of
      extracellular H(2)O(2) released from cells such as RAW 264.7 cells, which has
      potential utility to bioelectroanalytical chemistry, cellular biology, and
      pathophysiology.

PMID- 21170447
TI  - Luminescent zinc salen complexes as single and two-photon fluorescence
      subcellular imaging probes.
AB  - A novel class of ZnSalens (ZnL(1-10)) with lipophilic and cationic conjugates as
      optical probes in single and two-photon fluorescence microscopy images of living
      cells were prepared, which exhibited chemo- and photostability, low cytotoxicity
      and high subcellular selectivity.

PMID- 21170448
TI  - Silatranes: a review on their synthesis, structure, reactivity and applications.
AB  - This critical review summarizes progress of the rapidly developing and very
      active field of silatrane chemistry. The first part of the review deals with
      general synthetic approaches used to synthesize different silatranes. The most
      interesting feature of silatranes, i.e., variation of Si-N bond length on the
      basis of the axial substituent of Si, and other structural features, are
      described in the second part with special emphasis on crystallographic and
      theoretical studies. It is followed by a discussion on the reactivity of various
      silatranes. Silatranes have now gained acceptance for a wide variety of
      applications which are summarized in the last section of review. Some of them
      have extensive interest due to their medical use to heal wounds or stimulate hair
      growth (pilotropic activity), biological properties, pharmacological properties
      e.g. antitumor, anticancer, antibacterial, anti-inflammatory, fungicidal
      activity, stimulating effect in animal production and seed germination effects.
      The review focuses on the extended potential of silatranes in sol-gel processes,
      mesoporous zeotypes, atomic force microscopy, commercial products such as
      adhesion promoters, polymer formation and rubber compositions. This critical
      review will be helpful for general researchers, experts, advanced undergraduates
      and newcomers working on silatrane chemistry as this review presents greater
      emphasis on synthesis and characterization, structural properties, reactivity and
      applications of silatranes in the field of biology, material science, sol-gel
      chemistry, pharmaceutics, agriculture and medicine (311 references).

PMID- 21170449
TI  - A surface ionization detector for capillary gas chromatography.
AB  - A novel surface ionization detector using a reducing quartz liner and a Mo
      emitter with a quartz enclosed internal heater for selective measurement of
      alkylamines by gas chromatography is designed and evaluated.

PMID- 21170450
TI  - Hyper-thin organic membranes with exceptional H2/CO2 permeation selectivity:
      importance of ionic crosslinking and self-healing.
AB  - Single Langmuir-Blodgett (LB) bilayers derived from calix[n]arene-based
      surfactants (n = 4, 5 and 6) and poly(acrylic acid) (PAA) exhibit exceptional
      H(2)/CO(2) permeation selectivities. Evidence for the importance of ionic
      crosslinking and self-healing processes is presented.

PMID- 21170451
TI  - Synthetic, spectroscopic, and structural studies on organoimido molybdenum,
      tungsten, and rhenium phthalocyanines.
AB  - Unprecedented imido phthalocyaninato complexes of pentavalent refractory metals
      [PcM(NR)Cl] (M = Mo, W, Re; R = tBu: 1, 3, 6, Mes: 2, 4, 7 or Ts: 5) have been
      synthesized by reductive cyclotetramerization of phthalonitrile in the presence
      of appropriate bis(imido) complexes of Mo, W and Re as templates. While d(1)
      Mo(V) and W(V) species 1-5 show distinctive EPR spectra corresponding to metal
      centered radicals with hyperfine coupling of two magnetically non-equivalent
      nitrogen atoms (4 equatorial and 1 axial N), corresponding d(2) Re(V) compounds 6
      and 7 are diamagnetic. [PcMo(NtBu)Cl] 1 crystallizes from 1-chloronaphthalene in
      the tetragonal space group P4/n. The molecular structure reveals, that the metal
      center is located above the plane of the equatorial N4 and displaced towards the
      axial pi-donor ligand. Due to the thermodynamic trans effect the Mo-Cl bond trans
      to the imido group is elongated to about 2.600(2) A.

PMID- 21170452
TI  - In situ evaluation of lipase performances through dynamic asymmetric cyanohydrin
      resolution.
AB  - A dynamic resolution process based on multiple reversible cyanohydrin formation
      coupled to lipase-mediated transesterification is demonstrated. The resulting
      process resulted in the efficient evaluation of complex lipase performances in
      asymmetric cyanohydrin acylate synthesis. Dynamic systems were generated and
      resolved in situ, and the effects of the reaction conditions could be directly
      monitored for the overall system. By this concept, the enzyme activity, chemo-
      and stereoselectivity for all involved substrates could be simultaneously
      evaluated.

PMID- 21170453
TI  - An effective nanostructured assembly for ion-selective electrodes. An ionophore
      covalently linked to carbon nanotubes for Pb2+ determination.
AB  - We report on the synthesis of a new hybrid material, i.e. benzo-18-crown-6
      covalently linked to multi-wall carbon nanotubes, and its use in solid-state ion
      selective electrodes both as a receptor and an ion-to-electron transducer. This
      new concept leads to potentiometric sensors with extremely high selectivity.

PMID- 21170454
TI  - Simultaneous reduction-etching route to Pt/ZnSnO3 hollow polyhedral architectures
      for methanol electrooxidation in alkaline media with superior performance.
AB  - In this communication, a simultaneous reduction-etching route is exploited to
      fabricate Pt/ZnSnO(3) hollow polyhedra. The hollow ZnSnO(3) polyhedron is found
      to act as a novel and efficient support of Pt-based catalyst for methanol
      electrooxidation in alkaline media.

PMID- 21170455
TI  - Enhanced photoelectrochemical activities of a nanocomposite film with a bamboo
      leaf-like structured TiO2 layer on TiO2 nanotube arrays.
AB  - A novel nanocomposite TiO(2) film consisting of a bamboo leaf-like nano TiO(2)
      layer on a nanotubular TiO(2) arrays surface is synthesized by electrochemical
      anodization with wet chemical pretreatment; it shows almost three times higher
      activity as compared to that of nanotubular TiO(2) arrays alone.

PMID- 21170456
TI  - Chloride ion-catalyzed generation of difluorocarbene for efficient preparation of
      gem-difluorinated cyclopropenes and cyclopropanes.
AB  - A chloride ion-catalyzed generation of difluorocarbene from a relatively non
      toxic and inexpensive precursor, Me(3)SiCF(2)Cl (1), under mild and neutral
      conditions leads to an efficient preparation of gem-difluorocyclopropenes and
      difluorocyclopropanes through [2 + 1] cycloaddition reactions with alkynes and
      alkenes, respectively.

PMID- 21170457
TI  - A new synthetic route to chloride selective [2]catenanes.
AB  - A novel anion templation route has been developed to synthesise two new
      catenanes, which are observed to selectively complex chloride in protic solvent
      media.

PMID- 21170458
TI  - Facile preparation of Fe2O3 thin film with photoelectrochemical properties.
AB  - We report a simple approach for preparing undoped and Pt-doped Fe(2)O(3) thin
      films with excellent photoactivity via facile hydrothermal growth. The
      photocurrent densities of undoped and Pt-doped Fe(2)O(3) thin films were recorded
      up to 1.2 and 1.38 mA cm(-2) at 0.23 V Ag/AgCl under 1 sun illumination,
      respectively.

PMID- 21170459
TI  - Difluoro-boron-triaza-anthracene: a laser dye in the blue region. Theoretical
      simulation of alternative difluoro-boron-diaza-aromatic systems.
AB  - The synthesis, photophysical and laser properties of a difluoro-boron-triaza
      anthracene (BTAA) compound are analyzed in the present paper. The molecular
      structure of this dye is an anthracene-like core with N atoms at 4a, 9 and 10a
      positions where two of them (4a and 10a) are linked through a BF(2)-bridge group.
      This structure is reminiscent of aza-BODIPY dye with an s-indacene core, BODIPY
      being one of the most commonly used laser dye family in the Vis region. The main
      absorption and emission bands of the new dye are localized in the blue part of
      the Vis region of the electromagnetic radiation, a spectral region practically
      unexploited by the BODIPY chromophore. Moreover, the new dye presents a higher
      laser efficiency and photostability than other commercial laser dyes operating in
      the same spectral region. In order to look for new molecular structures with
      potential laser emission covering the whole Vis spectral region, the
      spectroscopic properties of other different chromophoric systems based on BF(2)
      linking aromatic groups are theoretically simulated by quantum mechanical
      calculations.

PMID- 21170460
TI  - Molecular and supramolecular dynamics of hybrid organic-inorganic interfaces for
      the rational construction of advanced hybrid nanomaterials.
AB  - Today the capability to rationally design and construct hybrid materials
      utilizing a performance-property driven methodology is strongly dependent on our
      ability to control the structure and the dynamics of hybrid interfaces. This
      control needs a deep knowledge of their molecular and supramolecular dynamics
      that must be evaluated in situ, in the soft matter or colloidal states. For this
      purpose the use of modern methodologies of characterization such as time resolved
      synchrotron experiments and advanced pulsed field gradient NMR methods (DOSY) is
      particularly relevant. In this critical review, two important examples are
      discussed. They concern, first, the study of surface capping organic components'
      affinity towards nanoparticle surfaces by DOSY NMR. The knowledge and therefore
      the tuning of this affinity is paramount because it controls solubility,
      transferability and stability of colloidal dispersions of nanoparticles (NPs). In
      the second part, the mechanism of micellar templated formation of hybrid
      mesophases will be discussed in the frame of the main results obtained via in
      situ SAXS (107 references).

PMID- 21170461
TI  - Heteroleptic Ir(III) complexes containing both azolate chromophoric chelate and
      diphenylphosphinoaryl cyclometalates; reactivities, electronic properties and
      applications.
AB  - The synthesis of a new family of octahedral Ir(III) complexes with dual
      cyclometalating phosphine chelates, namely: 1-(diphenylphosphino)naphthalene
      (dpnaH) and isoquinoline (dppiH), is reported. Two series of intermediate
      complexes, [Ir(dpna)(tht)(2)Cl(2)] (1), [Ir(dpna)(2)(OAc)] (2),
      [Ir(dppiH)(dppi)Cl(2)] (3) and [Ir(dppi)(2)(OAc)] (4), which can be classified by
      the coexistence of either a pair of cis-chlorides or a single acetate chelate,
      were obtained from treatment of phosphine with [IrCl(3)(tht)(3)] (tht =
      tetrahydrothiophene). The in situ generated acetate complexes 2 and 4 could react
      with azolate chelates, namely: 5-(2-pyridyl)-3-trifluoromethyl pyrazole (fppzH)
      and 5-(1-isoquinolyl)-3-tert-butyl-1,2,4-triazole (iqbtzH), to afford a new
      series of luminescent complexes [Ir(dpna)(2)(fppz)] (5a and 5b),
      [Ir(dpna)(2)(iqbtz)] (6a and 6b), [Ir(dppi)(2)(fppz)] (7a) and
      [Ir(dppi)(2)(iqbtz)] (8a). The phosphorescence lifetime (tau(obs)) fell in the
      range of a few tens of MUs, showing possession of excessive ligand-centered pipi*
      mixed in part with MLCT character. A density functional theory (DFT) study was
      also conducted in order to shed light on the origin of the transitions in the
      absorption and emission spectra and to predict emission energies for these
      complexes. Organic light emitting diodes (OLEDs) displaying bright orange
      emission and with maximum eta(ext) up to 17.1% were fabricated employing
      complexes 6a and 8a as the phosphorescent dopants.

PMID- 21170462
TI  - Demonstration of remote steric differentiation of cis/trans alkene coordination
      in copper(I) complexes of aryl-substituted bis(2-pyridyl)amine.
AB  - Complexes of the type [Cu(R-dpa)(eta(2)-olefin)]BF(4) (R = Mes and 2
      (i)PrC(6)H(4)) for cis- and trans- isomers of 3-octene, as well as those for cis-
      and trans-4-octene (R = 2-(i)PrC(6)H(4)) have been prepared and characterized by
      (1)H and (13)C NMR, FTIR, and TGA. The crystal structure of [Cu(Mes-dpa)(eta(2)
      trans-3-octene)]BF(4) (2) has been determined via X-ray crystallography. The
      asymmetric unit in the crystal lattice of 2 contains two unique conformations of
      the complex cation related by a pseudo center of symmetry, which differ primarily
      in the orientation of the olefin with respect to the rest of the molecule. The
      (1)H and (13)C NMR spectra of [Cu(Ar-dpa)(eta(2)-olefin)]BF(4) exhibit olefin
      resonances shifted upfield with respect to free olefin. The difference in
      Deltadelta((13)C) relative magnitudes between cis- and trans-complexes, i.e., the
      binding, correlates with the degree of substitution at the amine nitrogen. The
      identity of the remote ligand substituent (Ar) controls the differentiation of
      binding between cis and trans isomers as a consequence of increased folding of
      the Ar-dpa ligand along the Cu...N axis.

PMID- 21170463
TI  - Identification of geometrical isomers using vibrational circular dichroism
      spectroscopy: a series of mixed-ligand complexes of diamagnetic Co(III) ions.
AB  - Vibrational circular dichroism (VCD) spectra were measured on the chloroform
      solutions of a series of mixed-ligand diamagnetic Co(III) complexes,
      [Co(tfac)(n)(acac)(3-n)] (n = 0-3, tfac = 1,1,1-trifluoro-2,4-pentanedionato;
      acac = acetylacetonato). Distinct differences were observed in the VCD spectra
      among the geometrical isomers of the same ligand composition. Such
      differentiation was hardly possible by their infra-red spectra alone. The
      structural identification of these isomers was performed in conjunction with DFT
      calculations.

PMID- 21170464
TI  - Characterization of bacterial contaminants in the air of a duck hatchery by
      cultivation based and molecular methods.
AB  - Today's large-scale poultry production is often accompanied by high
      concentrations of airborne microorganisms at working places. However, the
      microbial communities in those bioaerosols are rarely characterised. In this
      study, we investigated the bacterial population in bioaerosols from a duck
      hatchery by both cultivation based and molecular methods and compared the
      results. Depending on used media, concentrations of airborne culturable bacteria
      varied between 6 * 10(1) and 7 * 10(6) CFU per m(3) air. The corresponding total
      cell count of DAPI stained cells was 2 * 10(7) cells per m(3) air. 16S rRNA gene
      analyses of bacterial isolates and clone libraries revealed a low species
      richness in hatcheries air, respectively. More than 50% of bacterial isolates
      were phylogenetically most closely related to bacterial species of the risk group
      2 (German TRBA). The sequence composition in clone libraries supported the result
      of cultivation based approaches, whereby sequences assigned to Staphylococcus,
      Acinetobacter and Enterococcus are the most common. The high concentration of
      airborne bacteria which are most closely related to species of potential health
      risk requires further detailed investigations for these bacterial species.

PMID- 21170465
TI  - Where are ionic liquid strategies most suited in the pursuit of chemicals and
      energy from lignocellulosic biomass?
AB  - Certain ionic liquids have been shown to dissolve cellulose, other biopolymers,
      and even raw biomass under relatively mild conditions. This particular ability of
      some ionic liquids, accompanied by a series of concurrent advantages, enables the
      development of improved processing strategies for the manufacturing of a plethora
      of biopolymer-based advanced materials. The more recent discoveries of
      dissolution of lignocellulosic materials (e.g., wood) in ionic liquids, with at
      least partial separation of the major constituent biopolymers, suggest further
      paths towards the achievement of a truly sustainable chemical and energy economy
      based on the concept of a biorefinery which provides chemicals, materials, and
      energy. Nonetheless, questions remain about the use of ionic liquids and the
      advisability of introducing any new process which utilizes bulk synthetic
      chemicals which have to be made, disposed of, and prevented from entering the
      environment. In this article, we discuss our own journey from the discovery of
      the dissolution of cellulose in ionic liquids to the cusp of an enabling
      technology for a true biorefinery and consider some of the key questions which
      remain.

PMID- 21170466
TI  - Acyl transfer from phosphocholine lipids to melittin.
AB  - Transfer of fatty acyl groups from membrane phospholipids to melittin, a commonly
      studied membrane-active peptide, has been observed to occur over extended time
      periods. Transfer can be detected after 1-2 days and selectively targets amino
      groups at the N-terminal end of the peptide.

PMID- 21170467
TI  - Microparticle ratiometric oxygen sensors utilizing near-infrared emitting quantum
      dots.
AB  - Luminescent sensors incorporating two luminophores, an indicator and a reference,
      offer many advantages over intensity measurements from sensors made with one
      indicator dye. Quantum dots have yet to be widely employed as insensitive
      reference luminophores in such systems. This work describes the use of near
      infrared emitting quantum dots in conjunction with a long-lifetime platinum(II)
      porphyrin phosphor in a microsphere-based, ratiometric oxygen sensor. The process
      for self-assembly of the nanocomposite system was developed, and the response and
      photostability of the prototypes were investigated. Results indicate the sensors
      possess excellent sensitivity (K(SV) = 0.00826 uM(-1)) at oxygen concentrations
      below 300 uM and were resistant to photobleaching. The sensor luminophores
      displayed minimal spectral overlap and little interference from excitation light,
      preventing the need for optical filters. A reversible photoenhancement of the
      quantum dot signal was also observed when exposed for extended periods of time.
      This work demonstrates the advantages of incorporating long-wavelength quantum
      dots into ratiometric intensity sensing schemes and highlights some key
      limitations that must be considered in their use.

PMID- 21170468
TI  - Mining health care administrative data with temporal association rules on hybrid
      events.
AB  - OBJECTIVE: The analysis of administrative health care data can be helpful to
      conveniently assess health care activities. In this context temporal data mining
      techniques can be suitably exploited to get a deeper insight into the processes
      underlying health care delivery. In this paper we present an algorithm for the
      extraction of temporal association rules (TARs) on sequences of hybrid events and
      its application on health care administrative databases. METHODS: We propose a
      method that extends TAR mining by managing hybrid events, namely events
      characterized by a heterogeneous temporal nature. Hybrid events include both
      point-like events (e.g. ambulatory visits) and interval-like events (e.g. drug
      consumption). The definition of user-defined rule templates can be optionally
      used to constrain the search only to the extraction of a subset of interesting
      rules. A TAR post-pruning strategy, based on a case-control approach, is also
      presented. RESULTS: We analyzed the administrative database of diabetic patients
      in charge to the regional health care agency (ASL) of Pavia. TAR mining allowed
      to find patterns specifically related to the diabetic population in comparison
      with a control group, as well as to check the compliance of the actual clinical
      careflow with the ASL recommendations. CONCLUSION: The experimental results
      highlighted the main potentials of the algorithm, such as the opportunity to
      detect interesting temporal relationships between diagnostic or therapeutic
      patterns, or to check the adherence of past temporal behaviors to specific
      expected paths (e.g. guidelines) or to discover new knowledge that could be
      implicitly hidden in the data.

PMID- 21170470
TI  - Development of ICF code selection tools for mental health care.
AB  - BACKGROUND: The International Classification of Functioning, Disability and
      Health (ICF) has been available as a means of coding life functions but the
      coding process is cumbersome due to the large number of ICF codes. In the current
      study, we developed ICF code selection tools to support the coding of activity
      and participation data recorded in domiciliary mental health care reports.
      METHODS: We first developed a search system to facilitate the selection of ICF
      codes by tracking back through codes' conceptual trees using a directory tool. We
      performed a morphological analysis on the training data set to correlate nouns
      with the ICF codes and obtained an analysis corpus to which numerical scores
      representing the frequencies of associated ICF codes for each noun were assigned.
      Based on the obtained corpus we developed a full-text search tool, which could
      simplify ICF coding relative to that performed using the directory tool. We then
      evaluated the usefulness of the former tool on the test data set. RESULTS: Using
      the full-text search tool, correct ICF codes were recorded in the first candidate
      list for only 54.2% of sentences. However, correct ICF codes appeared on the
      combined candidate lists for 90.1% of sentences and on the top three candidate
      lists for 71.7%. In a specific case (General Tasks and Demands), 100% of the
      correct codes were included on the combined candidate lists. CONCLUSION: We
      developed selection tools that effectively supported ICF coding, although it was
      impossible to fully automate ICF coding. This indicated that ICF codes could more
      effectively be applied to mental health care.

PMID- 21170469
TI  - Rapid assessment of clinical information systems in the healthcare setting: an
      efficient method for time-pressed evaluation.
AB  - OBJECTIVE: Recent legislation in the United States provides strong incentives for
      implementation of electronic health records (EHRs). The ensuing transformation in
      U.S. health care will increase demand for new methods to evaluate clinical
      informatics interventions. Timeline constraints and a rapidly changing
      environment will make traditional evaluation techniques burdensome. This paper
      describes an anthropological approach that provides a fast and flexible way to
      evaluate clinical information systems. METHODS: Adapting mixed-method evaluation
      approaches from anthropology, we describe a rapid assessment process (RAP) for
      assessing clinical informatics interventions in health care that we developed and
      used during seven site visits to diverse community hospitals and primary care
      settings in the U.S. SETTING: Our multidisciplinary team used RAP to evaluate
      factors that either encouraged people to use clinical decision support (CDS)
      systems or interfered with use of these systems in settings ranging from large
      urban hospitals to single-practitioner, private family practices in small towns.
      RESULTS: Critical elements of the method include: 1) developing a fieldwork
      guide; 2) carefully selecting observation sites and participants; 3) thoroughly
      preparing for site visits; 4) partnering with local collaborators; 5) collecting
      robust data by using multiple researchers and methods; and 6) analyzing and
      reporting data in a structured manner helpful to the organizations being
      evaluated. CONCLUSIONS: RAP, iteratively developed over the course of visits to
      seven clinical sites across the U.S., has succeeded in allowing a
      multidisciplinary team of informatics researchers to plan, gather and analyze
      data, and report results in a maximally efficient manner.

PMID- 21170471
TI  - Thromboelastometry (TEM) findings in disseminated intravascular coagulation in a
      pig model of endotoxinemia.
AB  - Standard coagulation tests have a low specificity and sensitivity for diagnosing
      disseminated intravascular coagulation. The aim of this study was to determine
      whether whole blood thromboelastometry (TEM) detects lipopolysaccharide (LPS)
      induced changes in coagulation. Blood samples from 10 pigs were drawn at
      baseline, before and at the end of LPS infusion and 2, 3, 4 and 5 h after the
      start of endotoxinemia. Simultaneous to TEM, standard coagulation tests and
      extended coagulation analysis including tissue plasminogen activator (t-PA) and
      plasminogen activator inhibitor 1 (PAI-1) were performed. Endotoxinemia resulted
      in a significant acceleration of the nonactivated TEM (NATEM) clotting time 2 h
      after the end of LPS infusion; in contrast, the changes in international
      normalized ratio and activated partial thromboplastin time suggested delayed
      initiation of coagulation. NATEM maximum clot firmness (MCF) and fibrin-based
      thromboelastometry test (FIBTEM)-MCF decreased significantly from baseline until
      the last time point (from 64.6 +/- 7.8 and 35.1 +/- 12.8 mm to 52.8 +/- 4.6 and
      21.4 +/- 11.8 mm, respectively; P = 0.01 for both parameters). A sharp, transient
      increase of t-PA had no effect on maximum lysis in the NATEM test. PAI-1
      increased significantly 3 h after the start of LPS infusion, paralleled by a
      decrease in maximum lysis. In conclusion, TEM was superior to standard
      coagulation tests in reflecting initial activation of coagulation during
      endotoxinemia. TEM further suggested consumption of coagulation substrate; at the
      same time, inhibition of plasminogen activation was accompanied by improved clot
      stability. Further investigations are necessary to establish the clinical
      relevance of these findings.

PMID- 21170472
TI  - Selective antihypertensive dihydropyridines lower Abeta accumulation by targeting
      both the production and the clearance of Abeta across the blood-brain barrier.
AB  - Several large population-based or clinical trial studies have suggested that
      certain dihydropyridine (DHP) L-type calcium channel blockers (CCBs) used for the
      treatment of hypertension may confer protection against the development of
      Alzheimer disease (AD). However, other studies with drugs of the same class have
      shown no beneficial clinical effects. To determine whether certain DHPs are able
      to impact underlying disease processes in AD (specifically the accumulation of
      the Alzheimer Abeta peptide), we investigated the effect of several
      antihypertensive DHPs and non-DHP CCBs on Abeta production. Among the
      antihypertensive DHPs tested, a few, including nilvadipine, nitrendipine and
      amlodipine inhibited Abeta production in vitro, whereas others had no effect or
      raised Abeta levels. In vivo, nilvadipine and nitrendipine acutely reduced brain
      Abeta levels in a transgenic mouse model of AD (Tg PS1/APPsw) and improved Abeta
      clearance across the blood-brain barrier (BBB), whereas amlodipine and nifedipine
      were ineffective showing that the Abeta-lowering activity of the DHPs is
      independent of their antihypertensive activity. Chronic oral treatment with
      nilvadipine decreased Abeta burden in the brains of Tg APPsw (Tg2576) and Tg
      PS1/APPsw mice, and also improved learning abilities and spatial memory. Our data
      suggest that the clinical benefit conferred by certain antihypertensive DHPs
      against AD is unrelated to their antihypertensive activity, but rely on their
      ability to lower brain Abeta accumulation by affecting both Abeta production and
      Abeta clearance across the BBB.

PMID- 21170473
TI  - A small nonerythropoietic helix B surface peptide based upon erythropoietin
      structure is cardioprotective against ischemic myocardial damage.
AB  - Strong cardioprotective properties of erythropoietin (EPO) reported over the last
      10 years have been difficult to translate to clinical applications for ischemic
      cardioprotection owing to undesirable parallel activation of erythropoiesis and
      thrombogenesis. A pyroglutamate helix B surface peptide (pHBP), recently
      engineered to include only a part of the EPO molecule that does not bind to EPO
      receptor and thus, is not erythropoietic, retains tissue protective properties of
      EPO. Here we compared the ability of pHBP and EPO to protect cardiac myocytes
      from oxidative stress in vitro and cardiac tissue from ischemic damage in vivo.
      HBP, similar to EPO, increased the reactive oxygen species (ROS) threshold for
      induction of the mitochondrial permeability transition by 40%. In an experimental
      model of myocardial infarction induced by permanent ligation of a coronary artery
      in rats, a single bolus injection of 60 MUg/kg of pHBP immediately after coronary
      ligation, similar to EPO, reduced apoptosis in the myocardial area at risk,
      examined 24 h later, by 80% and inflammation by 34%. Myocardial infarction (MI)
      measured 24 h after coronary ligation was similarly reduced by 50% in both pHBP-
      and EPO-treated rats. Two wks after surgery, left ventricular remodeling
      (ventricular dilation) and functional decline (fall in ejection fraction)
      assessed by echocardiography were significantly and similarly attenuated in pHBP-
      and EPO-treated rats, and MI size was reduced by 25%. The effect was retained
      during the 6-wk follow-up. A single bolus injection of pHBP immediately after
      coronary ligation was effective in reduction of MI size in a dose as low as 1
      MUg/kg, but was ineffective at a 60 MUg/kg dose if administered 24 h after MI
      induction. We conclude that pHBP is equally cardioprotective with EPO and
      deserves further consideration as a safer alternative to rhEPO in the search for
      therapeutic options to reduce myocardial damage following blockade of the
      coronary circulation.

PMID- 21170475
TI  - Professional education in Performing Arts Medicine.

PMID- 21170474
TI  - Differential effects of HNF-1alpha mutations associated with familial young-onset
      diabetes on target gene regulation.
AB  - Hepatocyte nuclear factor 1-alpha (HNF-1alpha) is a homeodomain transcription
      factor expressed in a variety of tissues (including liver and pancreas) that
      regulates a wide range of genes. Heterozygous mutations in the gene encoding HNF
      1alpha (HNF1A) cause familial young-onset diabetes, also known as maturity-onset
      diabetes of the young, type 3 (MODY3). The variability of the MODY3 clinical
      phenotype can be due to environmental and genetic factors as well as to the type
      and position of mutations. Thus, functional characterization of HNF1A mutations
      might provide insight into the molecular defects explaining the variability of
      the MODY3 phenotype. We have functionally characterized six HNF1A mutations
      identified in diabetic patients: two novel ones, p.Glu235Gly and c-57
      64delCACGCGGT;c-55G>C; and four previously described, p.Val133Met, p.Thr196Ala,
      p.Arg271Trp and p.Pro379Arg. The effects of mutations on transcriptional activity
      have been measured by reporter assays on a subset of HNF-1alpha target promoters
      in Cos7 and Min6 cells. Target DNA binding affinities have been quantified by
      electrophoretic mobility shift assay using bacterially expressed glutathione-S
      transferase (GST)-HNF-1alpha fusion proteins and nuclear extracts of transfected
      Cos7 cells. Our functional studies revealed that mutation c-57-64delCACGCGGT;c
      55G>C reduces HNF1A promoter activity in Min6 cells and that missense mutations
      have variable effects. Mutation p.Arg271Trp impairs HNF-1alpha activity in all
      conditions tested, whereas mutations p.Val133Met, p.Glu235Gly and p.Pro379Arg
      exert differential effects depending on the target promoter. In contrast,
      substitution p.Thr196Ala does not appear to alter HNF-1alpha function. Our
      results suggest that HNF1A mutations may have differential effects on the
      regulation of specific target genes, which could contribute to the variability of
      the MODY3 clinical phenotype.

PMID- 21170476
TI  - Treatment of music performance anxiety via psychological approaches: a review of
      selected CBT and psychodynamic literature.
AB  - Performance anxiety, or stage fright, is anxiety aroused about potential mishaps
      in performance that expose feared inadequacies before an audience and which evoke
      feelings of embarrassment and humilation. For affected musicians, performance
      anxiety can be emotionally devastating, as their career choice in music may be
      terminated or severely compromised. This paper focuses on the cognitive and
      psychodynamic literature about music performance anxiety, with the emphasis that
      for treatment "one size does not fit all." It reviews the factors underlying
      performance anxiety and those factors which can exacerbate the condition in
      musicians. The two major clinical treatment modalities within contemporary
      psychology, cognitive behavior therapy (CBT) and psychodynamic treatments, are
      reviewed. While there are more empirical studies of CBT in various populations in
      the literature, until recently there was an indifference to empirical research by
      psychodynamic investigators. However, meta-analyses show strong efficacy for
      psychodynamic psychotherapy (in various disorders, not specifically music
      performance anxiety), but also that the benefits of psychodynamic psychotherapy
      may endure longer and increase with time.

PMID- 21170477
TI  - A combination of constraint-induced therapy and motor control retraining in the
      treatment of focal hand dystonia in musicians.
AB  - Focal hand dystonia (FHD) in musicians is a painless task-specific motor disorder
      characterized by an involuntary loss of control of individual finger movements.
      The aim of this study was to investigate the effects of an innovative behavioural
      therapy intervention, aimed at normalising movement patterns, in musicians
      affected by FHD. METHODS: Eight musicians volunteered to take part in this
      retraining protocol. Intensive constraint-induced therapy and motor control
      retraining at slow speed were the interventions. Video recordings of the subjects
      playing two pieces were used for data analysis. The Frequency of Abnormal
      Movements scale (FAM), the change in metronome speed achieved during motor
      control retraining, and two ordinal dystonia evaluation scales were chosen as
      outcome measures. It was hypothesised that there would be significant differences
      in the FAM scores and metronome speeds over a 12-month period. RESULTS: For the
      main outcome measure, the FAM scale scores, the two-factor repeated measures
      ANOVA revealed a very significant decrease in the number of abnormal movements
      per second of instrumental playing over the 12-month period (F = 6.32, df = 7, p
      < 0.001). Tukey's post-hoc tests carried out for the FAM scores revealed that
      significant changes occurred after 8 months of therapy. DISCUSSION: These results
      suggest that a combination of constraint-induced therapy and specific motor
      control retraining may be a successful strategy for the treatment of musicians'
      FHD. Furthermore, the results suggest that retraining strategies may need to be
      carried out for at least 8 months before statistically significant changes are
      noted.

PMID- 21170478
TI  - Reliability of anthropometric measurements in young male and female artistic
      gymnasts.
AB  - Body dimensions and body composition of children participating in artistic
      activities, such as gymnastics and many types of dancing, are important factors
      in performance improvement. The present study aimed to determine the reliability
      of a series of selected anthropometric measurements in young male and female
      gymnasts. Segment lengths, body breadths, circumferences, and skinfold thickness
      were measured in 20 young gymnasts by the same experienced examiner, using
      portable and easy-to-use instruments. All parameters were measured twice (test
      retest) under the same conditions within a week's period. The high intra-class
      correlation coefficient (ICC) values ranging from 0.87 to 0.99, as well as the
      low coefficient of variation (CV) values (<5.3%), affirmed that the selected
      measurements were highly reliable. The technical error of measurement (TEM)
      values for lengths and breadths were 0.15 to 0.80 cm, for circumferences 0.22 to
      1 cm, and for skinfold thickness 0.33 to 0.58 mm. The high test-retest ICC and
      the low CV and TEM values confirmed the reliability of all anthropometric
      measurements in young artistic gymnasts. Therefore, these measurements could
      contribute to further research in this field of investigation, helping to monitor
      young artistic gymnasts' growth status and identify specific characteristics for
      increased performance in this sport.

PMID- 21170479
TI  - Hand biomechanics in skilled pianists playing a scale in thirds.
AB  - Pianists, who attend to the integral relationship of their particular
      musculoskeletal characteristics to the piano technique at hand, discover an
      efficient path to technical advancement and, consequently, to injury prevention.
      Thus, a study of pianist's hand biomechanics in relation to different piano
      techniques is highly relevant, as hand features may influence various techniques
      in different ways. This study addressed relationships between pianists' hand
      biomechanics and the performance of a scale in thirds, as a part of an ongoing
      series of studies examining relationships between hand biomechanics and
      performance data of primary techniques. The biomechanics of hand length and
      width, finger length, hand span, hand and arm weights, and ulnar deviation at the
      wrist were compared with tempo, articulation, and dynamic voicing (tone balance
      between two notes of the thirds). Pearson correlation analysis showed a positive
      association between ulnar deviation and tempo; the other biomechanical features
      showed no relationships with any of the performance criteria. Qualitative cross
      sectional observation of individual profiles showed that experienced pianists
      perform with a higher degree of synchrony in two-note descent while pianists with
      organ training background play with a lesser degree of synchrony. All
      biomechanical features were closely related among one another with one exception:
      wrist ulnar deviation was not associated with any other biomechanical features;
      rather, data suggest possible negative associations. This study underscores the
      importance of wrist mobility in piano skills development. Further research using
      a complete set of prototype piano techniques and multiple-level pianist-subjects
      could provide substantive biomechanical information that may be used to develop
      efficient pedagogy and prevention strategies for playing-related injuries as well
      as rehabilitation.

PMID- 21170480
TI  - Potential hazard of hearing damage to students in undergraduate popular music
      courses.
AB  - In recent years, there has been a rapid growth in university courses related to
      popular and commercial music, with a commensurate increase in the number of
      students studying these courses. Students of popular music subjects are
      frequently involved in the use of electronically amplified sound for rehearsal
      and recording, in addition to the "normal" noise exposure commonly associated
      with young people. The combination of these two elements suggests a higher than
      average noise exposure hazard for these students. To date, the majority of noise
      studies on students have focused on exposure from personal music players and on
      classical, orchestral, and marching band musicians. One hundred students across a
      range of university popular music courses were surveyed using a 30-point
      questionnaire regarding their musical habits both within and external to their
      university courses. This was followed by noise dosimetry of studios/recording
      spaces and music venues popular with students. Questionnaire responses showed 76%
      of subjects reported having experienced symptoms associated with hearing loss,
      while only 18% reported using hearing protection devices. Rehearsals averaged
      11.5 hrs/wk, with a mean duration 2 hrs 13 mins and mean level of 98 dB LAEQ.
      Ninety-four percent of subjects reported attending concerts or nightclubs at
      least once per week, and measured exposure in two of these venues ranged from 98
      to 112 dB LAEQ with a mean of 98.9 dB LAEQ over a 4.5-hr period. Results
      suggested an extremely high hazard of excessive noise exposure among this group
      from both their social and study-based music activities.

PMID- 21170481
TI  - Functional anatomy of the soft palate applied to wind playing.
AB  - Wind players must be able to sustain high intraoral pressures in order to play
      their instruments. Prolonged exposure to these high pressures may lead to the
      performance-related disorder velopharyngeal insufficiency (VPI). This disorder
      occurs when the soft palate fails to completely close the air passage between the
      oral and nasal cavities in the upper respiratory cavity during blowing tasks,
      this closure being necessary for optimum performance on a wind instrument. VPI is
      potentially career threatening. Improving music teachers' and students' knowledge
      of the mechanism of velopharyngeal closure may assist in avoiding potentially
      catastrophic performance-related disorders arising from dysfunction of the soft
      palate. In the functional anatomy of the soft palate as applied to wind playing,
      seven muscles of the soft palate involved in the velopharyngeal closure mechanism
      are reviewed. These are the tensor veli palatini, levator veli palatini,
      palatopharyngeus, palatoglossus, musculus uvulae, superior pharyngeal
      constrictor, and salpingopharyngeus. These muscles contribute to either a palatal
      or a pharyngeal component of velopharyngeal closure. This information should
      guide further research into targeted methods of assessment, management, and
      treatment of VPI in wind musicians.

PMID- 21170482
TI  - Heavy metal accumulation in soil amended with roadside pond sediment and uptake
      by winter wheat (Triticum aestivum L. cv. PBW 343).
AB  - The risks of heavy metal accumulation and the dynamics related to roadside pond
      sediment application in comparison to control of winter wheat (Triticum aestivum
      L.) were investigated in field experiments. Selective sequential extraction
      procedures revealed that application of pond sediment in soil increases the
      labile pools of the studied heavy metals (Cd, Cr, Cu, Ni, Pb, and Zn). Risk
      assessment codes concluded that Cu and Pb were in the high-risk zone in both pond
      sediment and soil amended with pond sediment, whereas Zn and Cu were found in the
      medium-risk zone for control soil. Heavy metal accumulation by wheat straw and
      grain (39.38, 1.18, 23.73, 0.36, 0.18, and 16.8 mg kg-1 for Zn, Cd, Cu, Cr, Ni,
      and Pb, respectively, for wheat grain) was significantly increased through
      application of pond sediment. However, metal accumulation did not thwart the
      enhancement of wheat yield when pond sediment was applied. Health risk indexes of
      analyzed heavy metals were found to be within the Indian permissible limit for
      foodstuffs. Pond sediments help to fortify wheat grain by increasing the
      concentration of Zn and Cu as a source of micronutrients in the diet. However, a
      significant increase of Pb in wheat grain through pond sediment could be a health
      concern for its long-term application. Therefore, pond sediment would be a
      valuable resource for agriculture as an alternative organic supplement, but long
      term use may require the cessation of the excavated sediment as agricultural
      landfill in order to restrict heavy metal contamination through it.

PMID- 21170483
TI  - A review of three simple plant models and corresponding statistical tools for
      basic research in homeopathy.
AB  - In this paper, we review three simple plant models (wheat seed germination, wheat
      seedling growth, and infected tobacco plants) that we set up during a series of
      experiments carried out from 1991 to 2009 in order to study the effects of
      homeopathic treatments. We will also describe the set of statistical tools
      applied in the different models. The homeopathic treatment used in our
      experiments was arsenic trioxide (As2O3) diluted in a decimal scale and
      dynamized. Since the most significant results were achieved with the 45th decimal
      potency, both for As2O3 (As 45x) and water (W 45x), we here report a brief
      summary of these results. The statistical analysis was performed by using
      parametric and nonparametric tests, and Poisson distribution had an essential
      role when dealing with germination experiments. Finally, we will describe some
      results related to the changes in variability, which seems to be one of the
      targets of homeopathic treatment effect.

PMID- 21170484
TI  - Lepromatous leprosy: a commonly misdiagnosed disease.

PMID- 21170485
TI  - Pre- and postnatal management of hydronephrosis.

PMID- 21170486
TI  - Active surveillance for localized prostate cancer--current practices and
      recommendations.
AB  - Prostate cancer is now the most commonly diagnosed solid tumor in American men,
      due in part to widespread screening and aggressive diagnostic practices. Prostate
      cancer autopsy studies show the uniquely high prevalence rates of small, indolent
      tumors in men dying of other causes. These findings have led to increased concern
      for the over detection and overtreatment of prostate cancer. Active surveillance
      for prostate cancer allows one to limit prostate cancer treatment with
      concomitant risks of treatment-related morbidity to the men who will benefit the
      most from aggressive therapies. Several tools have been developed in treated and
      surveyed men to assist physicians in selecting men with potentially indolent
      tumors amenable to active surveillance. Recent published results describe
      institutional experiences with active surveillance and delayed selective therapy
      for men with low-grade, early prostate cancer. Although median follow-up from
      these studies is relatively short, the outcomes appear favorable. Data from these
      reports provide information for selecting men for this approach, as well as for
      following them over time and determining triggers for further intervention.
      Ongoing clinical trials with watchful waiting and active surveillance for
      prostate cancer will ultimately provide improved evidence for managing early,
      localized disease.

PMID- 21170487
TI  - Halofuginone- and chitosan-coated amnion membranes demonstrate improved abdominal
      adhesion prevention.
AB  - Our objective was to determine whether coating the amniotic membrane with
      halofuginone, a type 1 collagen synthase inhibitor, with or without the
      hemostasis-inducing substance chitosan, reduced the number and severity of
      adhesions in the rat uterine horn injury model. Sixty retired breeder Sprague
      Dawley rats underwent midline laparotomy and a zone of ischemia was created in
      the left uterine horn of each animal. Rats were randomized to one of six
      treatment groups: (1) untreated control, (2) oxidized regenerated cellulose
      (Interceed(r)) (ORC), (3) plain amnion, (4) amnion coated on both sides with 0.5%
      solution of halofuginone (HAH), (5) amnion coated on one side with 0.5%
      halofuginone and on the other side with chitosan (CAH), or (6) amnion coated on
      both sides with chitosan (CAC). The zone of ischemia in each left uterine horn
      was wrapped in each treatment. Rats were sacrificed 2 weeks after laparotomy, and
      adhesions were counted and scored for severity. Data were analyzed using Chi
      square and a p < 0.05 was considered significant. Our results showed that there
      were no differences in the percentage of animals with adhesions in the untreated,
      ORC, plain amnion, or CAC groups. No adhesions formed in any animal in the HAH
      group and only 14% of the animals developed adhesions to the uterine horn in the
      CAH group (p < 0.05). The percentage of animals with moderate and severe
      adhesions did not differ between untreated controls and the ORC groups, but were
      significantly reduced in all four of the amnion groups: plain amnion, HAH, CAH,
      and CAC (p < 0.05). Amnion coated with halofuginone alone or in combination with
      chitosan reduced the percentage of animals with adhesions, as well as the
      percentage of animals with moderate and severe adhesions compared to untreated
      controls and the ORC group in the rat uterine horn injury model. Amnion alone or
      coated with chitosan reduced the percentage of rats with moderate and severe
      adhesions, but not the percentage of rats with adhesions of any type compared to
      both untreated controls and the ORC group in the rat uterine horn injury model.

PMID- 21170488
TI  - The role of the TGF-beta coreceptor endoglin in cancer.
AB  - Endoglin (CD105) is an auxiliary membrane receptor of transforming growth factor
      beta (TGF-beta) that interacts with type I and type II TGF-beta receptors and
      modulates TGF-beta signaling. Endoglin is overexpressed in the tumor-associated
      vascular endothelium, where it modulates angiogenesis. This feature makes
      endoglin a promising target for antiangiogenic cancer therapy. In addition,
      recent studies on human and experimental models of carcinogenesis point to an
      important tumor cell-autonomous role of endoglin by regulating proliferation,
      migration, invasion, and metastasis. These studies suggest that endoglin behaves
      as a suppressor of malignancy in experimental and human epithelial
      carcinogenesis, although it can also promote metastasis in other types of cancer.
      In this review, we evaluate the implication of endoglin in tumor development
      underlying studies developed in our laboratories in recent years.

PMID- 21170489
TI  - The production of the oral mucosa of antiendomysial and anti-tissue
      transglutaminase antibodies in patients with celiac disease: a review.
AB  - Celiac disease (CD) is a lifelong, T cell-mediated enteropathy, triggered by the
      ingestion of gluten and related prolamins in genetically susceptible subjects,
      resulting in minor intestinal mucosal injury, including villous atrophy with
      crypt hyperplasia and intraepithelial lymphocytosis, and subsequent nutrient
      malabsorption. Although serological tests for antiendomysial (EMA) and anti
      tissue transglutaminase (anti-tTG) autoantibodies are used to screen and follow
      up on patients with CD, diagnostic confirmation is still based on the
      histological examination of the small intestinal mucosa. Although the small
      intestinal mucosa is the main site of the gut involved in CD, other mucosal
      surfaces (such as gastric, rectal, ileal, and esophageal) belonging to the
      gastrointestinal tract and the gut-associated lymphoid tissue (GALT) can also be
      involved. A site that could be studied less invasively is the mouth, as it is the
      first part of the gastrointestinal system and a part of the GALT. Indeed, not
      only have various oral ailments been reported as possible atypical aspects of CD,
      but it has been also demonstrated that inflammatory changes occur after oral
      supramucosal application and a submucosal injection of gliadin into the oral
      mucosa of CD patients. However, to date, only two studies have assessed the
      capacity of the oral mucosa of untreated CD patients to EMA and anti-tTG
      antibodies. In this paper, we will review studies that evaluate the capacity of
      the oral mucosa to produce specific CD autoantibodies. Discrepancies in
      sensitivity from the two studies have revealed that biopsy is still not an
      adequate procedure for the routine diagnostic purposes of CD patients, and a more
      in-depth evaluation on a larger sample size with standardized collection and
      analysis methods is merited. However, the demonstration of immunological
      reactivity to the gluten ingestion of the oral mucosa of CD, in terms of IgA EMA
      and anti-tTG production, needs to be further evaluated in order to verify whether
      the oral mucosa is colonized by lymphocytes activated in the intestine or if
      gluten could stimulate naive lymphocytes directly in the oral mucosa. This would
      have important implications for the pathogenesis, diagnosis, and treatment of CD.

PMID- 21170491
TI  - Montelukast: more than a cysteinyl leukotriene receptor antagonist?
AB  - The prototype cysteinyl leukotriene receptor antagonist, montelukast, is
      generally considered to have a niche application in the therapy of exercise- and
      aspirin-induced asthma. It is also used as add-on therapy in patients whose
      asthma is poorly controlled with inhaled corticosteroid monotherapy, or with the
      combination of a long-acting beta(2)-agonist and an inhaled corticosteroid.
      Recently, however, montelukast has been reported to possess secondary anti
      inflammatory properties, apparently unrelated to conventional antagonism of
      cysteinyl leukotriene receptors. These novel activities enable montelukast to
      target eosinophils, monocytes, and, in particular, the corticosteroid-insensitive
      neutrophil, suggesting that this agent may have a broader spectrum of anti
      inflammatory activities than originally thought. If so, montelukast is
      potentially useful in the chemotherapy of intermittent asthma, chronic
      obstructive pulmonary disease, cystic fibrosis, and viral bronchiolitis, which,
      to a large extent, involve airway epithelial cell/neutrophil interactions. The
      primary objective of this mini-review is to present evidence for the cysteinyl
      leukotriene-independent mechanisms of action of montelukast and their potential
      clinical relevance.

PMID- 21170490
TI  - Role of C5 activation products in sepsis.
AB  - Complement activation products are known to be generated in the setting of both
      experimental and human sepsis. C5 activation products (C5a anaphylatoxin and the
      membrane attack complex [MAC] C5b-9) are generated during sepsis following
      infusion of endotoxin, or after cecal ligation and puncture (CLP), which produces
      polymicrobial sepsis. C5a reacts with its receptors C5aR and C5L2 in a manner
      that creates the "cytokine storm", and is associated with development of
      multiorgan failure (MOF). A number of other complications arising from the
      interaction of C5a with its receptors include apoptosis of lymphoid cells, loss
      of innate immune functions of neutrophils (PMNs, polymorphonuclear leukocytes),
      cardiomyopathy, disseminated intravascular coagulation, and complications
      associated with MOF. Neutralization of C5a in vivo or absence/blockade of C5a
      receptors greatly reduces the adverse events in the setting of sepsis, markedly
      attenuates MOF, and greatly improves survival. Regarding the possible role of C5b
      9 in sepsis, the literature is conflicting. Some studies suggest that C5b-9 is
      protective, while other studies suggest the contrary. Clearly, in human sepsis,
      C5a and its receptors may be logical targets for interception.

PMID- 21170492
TI  - [Effects of amyloid beta-protein on hippocampal long-term potentiation].
AB  - The accumulation of amyloid beta-protein (Abeta) plaques is identified as a major
      pathological feature of Alzheimer's disease (AD). Recent studies show that
      soluble species of Abeta are involved in the early memory dysfunction long before
      neurodegenerative changes. However, the mechanism underlying the neurotoxicity of
      soluble Abeta is still unclear. Long-term potentiation (LTP) has been thought as
      an important cellular model of synaptic plasticity for many years. The studies on
      the hippocampal LTP and Abeta, especially those using AD transgenic models,
      provided more evidence for the Abeta-induced dysfunction of learning and memory.
      Based on the recent researches on AD, this article reviewed the effects of Abeta,
      especially soluble Abeta and its active fragments, on the hippocampal LTP. The
      possible mechanisms by which Abeta impairs hippocampal LTP are also discussed.

PMID- 21170493
TI  - [Hippocampal cAMP response element binding protein and antidepressant
      treatments].
AB  - With the deepening research on pathogenesis of depression, the focus has diverted
      from the mechanism of regulating monoamines to the basic pathophysiology of
      depression and the long-term mechanism of antidepressant treatments. cAMP
      response element binding protein (CREB) in the brain, especially in the
      hippocampi, as a converging agent of many intracellular signaling transduction
      pathways is getting increasing attention. To better understand the basic
      pathophysiology of depression and the long-term mechanism of antidepressant
      treatments, it is significant to make clear the correlation between hippocampal
      CREB and antidepressant treatments. This review mainly refers to the formation of
      CREB and its distribution in hippocampi, the upstream signaling transduction
      pathways of hippocampal CREB and antidepressant treatments, and the possible
      antidepressant mechanisms by regulating hippocampal CREB.

PMID- 21170494
TI  - ["Waste gas is not waste": advance in the research of hydrogen sulfide].
AB  - The discovery of endogenous gasotransmitters puts forwards a new concept, "waste
      gas is not waste". Hydrogen sulfide (H(2)S) is considered as a new member of
      gasotransmitter family, following nitric oxide (NO) and carbon monoxide (CO).
      Recently, the understanding of H(2)S biological effect and its mechanisms has
      been deepened, especially the pathophysiological significance of H(2)S in the
      various diseases such as cardiovascular diseases, neurological diseases,
      respiratory diseases, endocrine diseases, etc. This article reviews recent
      progress of basic, clinical and pharmacological researches related to endogenous
      H(2)S, including the regulatory effects of H(2)S on the cell proliferation,
      apoptosis, inflammation, angiogenesis and ion channels, the role of endogenous
      H(2)S pathway in the pathogenesis of various diseases, as well as the study of
      the H(2)S donor and H(2)S-related drugs.

PMID- 21170495
TI  - [Overexpression of beta(1)-adrenoceptor can not protect rat cardiomyocytes from
      injury induced by isoprenaline].
AB  - The purpose of this study was to investigate the effect of the overexpression of
      beta(1)-adrenoceptor (beta(1)-AR) on the contractile function and cell survival
      of rat cardiomyocytes injured by isoprenaline (ISO). The rat cardiomyocytes were
      isolated using the collagenase perfusion method and then transfected with beta(1)
      AR gene using adenoviruses vector. Four hours after the infection, the rat
      cardiomyocytes were treated with ISO for 24 h to imitate the high catecholamine
      levels of chronic heart failure. Western blot was performed to measure the
      protein expression of beta(1)-AR. The percentages of rod cells were measured to
      test cell survival. Video-based edge-detection system was used to measure the
      contractile function of the cardiomyocytes. The results indicated that the
      expression of beta(1)-AR in beta(1)-AR-transfected cardiomyocytes was
      significantly increased compared with that in control group (P<0.01). Meanwhile,
      beta(1)-AR transfection also increased beta(1)-AR protein levels in ISO-injured
      cardiomyocytes. The cardiomyocyte survival was significantly decreased in ISO
      group compared with that in control group. beta(1)-AR-transfection alone had no
      effect on cardiomyocyte survival in beta(1)-AR group, but it further decreased
      cardiomyocyte survival in beta(1)-AR+ISO group. Contractile amplitudes of ISO
      injured cardiomyocytes were significantly decreased regardless of whether they
      were transfected with beta(1)-AR or not, although beta(1)-AR-transfected
      cardiomyocytes showed significantly increased contractile function compared with
      control group (P<0.05). These results suggest that the overexpression of beta(1)
      AR has no significant protective effect on rat cardiomyocytes injured by ISO.

PMID- 21170496
TI  - [Overexpression of SERCA2a by gene transfer enhances myocardial systolic function
      in canines].
AB  - The present study is aimed to study the effect of sarcoplasmic reticulum Ca(2+)
      ATPase 2a (SERCA2a) gene transfer on the contractile function of isolated
      cardiomyocytes of canines. The cardiomyocytes were isolated with collagenases.
      The isolated cardiac cells were divided into untransfected group, empty vector
      group and SERCA2a-transfected group. Recombinant adenovirus vector carrying
      enhanced green fluorescent protein gene was used for SERCA2a gene delivery. The
      expression of SERCA2a protein in cardiomyocytes was determined by Western blot.
      Contractile function of cardiomyocytes was measured with motion edge-detection
      system of single cell at 48 h after transfection. The results showed, compared
      with untransfected group, SERCA2a protein level, percentage of peak contraction
      amplitude under normal condition, percentages of peak contraction amplitude under
      Ca(2+) or isoproterenol stimulation, time-to-peak contraction (TTP) and time-to
      50% relaxation (R50) in SERCA2a-transfected group all increased significantly.
      While all the above indices in empty vector group did not show any differences
      with those in untransfected group. These results suggest that the overexpression
      of SERCA2a by gene transfer may enhance the contraction function of canine
      myocardial cells.

PMID- 21170497
TI  - [Cardiac hypertrophy and changes in contractile function of cardiomyocyte].
AB  - To investigate the cellular mechanisms of pressure-overload cardiac hypertrophy
      transition to heart failure, we observed time course of changes in morphology and
      contractile function of cardiomyocytes in transverse abdominal aortic
      constriction (TAC) rats. Since TAC rats suffered higher stress, body weight had a
      slower growth rate compared with that of synchronous control rats. Therefore, the
      left ventricular to body weight ratio produced experimental bias to evaluate the
      degree of cardiac hypertrophy. Length and width of collagenase-isolated
      cardiomyocyte were directly measured. Length, width and calculated surface area
      of cardiomyocyte showed a progressive increase in 8-, 16-, and 20-week TAC rats.
      The increasing rate of surface area in cardiomyocytes was higher at the middle
      stage of TAC (from the eighth to sixteenth week). Due to the constraint of
      fibrosis formation, the increasing rate of surface area in cardiomyocytes was
      slower at the late stage of TAC (from the sixteenth to twentieth week). The
      sarcomere length of cardiomyocytes was unchanged, whereas sarcomere numbers were
      significantly increased in 8-, 16-, and 20-week TAC rats. Shortening amplitude of
      unloaded contraction in single cardiomyocyte was significantly enhanced in 1-week
      TAC rats, but not altered in 8-week TAC rats compared with that in the
      synchronous control rats. On the contrary, unloaded shortening amplitude of
      single cardiomyocyte was significantly reduced in 16- and 20-week TAC rats. The
      above results suggest that the reduced shortening amplitude may be associated
      with intrinsic molecular alterations in hypertrophied cardiomyocytes.

PMID- 21170498
TI  - [The expression of a novel estrogen receptor, GPR30, in epithelial ovarian
      carcinoma and its correlation with MMP-9].
AB  - The aim of the present study is to investigate the expression of a novel estrogen
      receptor, G protein-coupled receptor 30 (GPR30) and its correlation with matrix
      metalloproteinases-9 (MMP-9) in epithelial ovarian cancer (EOC). Ovary tissues
      were obtained from 39 female patients, including 30 cases of EOC and 9 cases of
      benign ovarian tumor. Four normal ovary tissues were used as control.
      Immunohistochemical staining was used to detect the expressions of GPR30 and MMP
      9. Chi square test, Fisher's exact test and Spearman's rank correlation analysis
      were used for statistical analysis. The results showed that GPR30 overexpression
      rate in EOC cases was significantly higher than those in benign ovarian tumor and
      normal ovary cases. Whereas MMP-9 overexpression rate in EOC cases was
      significantly higher than that in normal ovary cases, without any difference to
      that in benign ovarian tumor cases. To demonstrate the relationship between GPR30
      and clinicopathological variables of EOC, we further analyzed the pathology type,
      FIGO stage and age of patients sampled in our study. The analysis showed there
      were significant differences of GPR30 overexpression rate among various pathology
      types and different FIGO stages (P<0.05), and no significant difference of both
      GPR30 and MMP-9 among three age groups (P>0.05). Moreover, GPR30 expression was
      positively correlated with MMP-9 (r(s)=1.000, P=0.002). These results suggest
      that GPR30 may be involved in the invasion and metastasis of EOC, being a
      potential index of EOC early diagnosis and malignancy grade prediction.

PMID- 21170499
TI  - [Effects of linoleic acid on intracellular calcium concentration in primarily
      cultured rat pancreatic beta-cells and underlying mechanism].
AB  - In this study, we investigated the mechanism of linoleic acid-stimulated increase
      in intracellular calcium concentration ([Ca(2+)](i)) in pancreatic islet beta
      cells. Pancreatic islet cells were primarily isolated from rats and cultured for
      the experiments. The cells were loaded with Fluo-3/AM, the indicator of
      [Ca(2+)](i), and the intensity of Fluo-3 was measured using confocal microscope.
      The islet beta-cells were identified by immunocytochemical staining with insulin
      antibody after recording. The drugs were given by perfusion system. The results
      showed that linoleic acid (20 MUmol/L) stimulated [Ca(2+)](i) increase with the
      first peak increase and the following plateau increase. Linoleic acid-stimulated
      [Ca(2+)](i) increase was partly inhibited by removal of extracellular calcium and
      by transient receptor potential (TRP) channel blocker, La(3+), and it was totally
      blocked by exhaustion of intracellular calcium stores and inhibition of
      phospholipase C. It is concluded that linoleic acid stimulates [Ca(2+)](i)
      increase in islet beta-cells through both extracellular calcium influx via TRP
      channels and calcium release from intracellular calcium stores.

PMID- 21170500
TI  - [Baicalin prevents the up-regulation of connective tissue growth factor in
      fibrotic lungs of rats].
AB  - To clarify the mechanism underlying the preventive effect of baicalin (Bai) on
      fibrosis in lung, we investigated the influence of Bai on the up-regulation of
      connective tissue growth factor (CTGF) in fibrotic lungs. Male Sprague-Dawley
      (SD) rats were divided into four groups randomly: normal saline (NS)+NS group (a
      single intratracheal instillation of NS plus i.p. injection of NS), NS+Bai group
      (intratracheal instillation of NS plus i.p. injection of Bai), bleomycin (BLM)+NS
      group (intratracheal instillation of BLM plus i.p. injection of NS) and BLM+Bai
      group (intratracheal instillation of BLM plus i.p. injection of Bai). All the
      i.p. injections were performed once daily. On day 28 after intratracheal
      instillation of BLM or NS, the rats were sacrificed for lung tissue sampling. As
      the index of the severity of pulmonary fibrosis, the content of hydroxyproline in
      lungs was analyzed by chloramine T method. The expression levels of CTGF mRNA and
      protein in the lungs were detected by RT-PCR and immunohistochemistry,
      respectively. The results showed that, compared to the rats in NS+NS group, the
      rats in BLM+NS group showed increased hydroxyproline content and higher levels of
      CTGF mRNA and protein expressions (P<0.01), suggesting that BLM had induced
      fibrosis in lung and up-regulated CTGF expression in the fibrotic lungs.
      Administration of different dosages of Bai (6, 12.5 and 50 mg/kg per d, for 28
      days) into the BLM-treated rats reduced the increased content of hydroxyproline,
      and ameliorated the up-regulation of CTGF mRNA and protein levels, respectively.
      These results suggest that Bai could prevent the up-regulation of CTGF expression
      in fibrotic lungs of rats receiving BLM instillation, which might be one of the
      mechanisms underlying the preventive effect of Bai on pulmonary fibrosis.

PMID- 21170501
TI  - The body weight loss during acute exposure to high-altitude hypoxia in sea level
      residents.
AB  - Weight loss is frequently observed after acute exposure to high altitude.
      However, the magnitude and rate of weight loss during acute exposure to high
      altitude has not been clarified in a controlled prospective study. The present
      study was performed to evaluate weight loss at high altitude. A group of 120 male
      subjects [aged (32+/-6) years] who worked on the construction of the Golmud-Lhasa
      Railway at Kunlun Mountain (altitude of 4 678 m) served as volunteer subjects for
      this study. Eighty-five workers normally resided at sea level (sea level group)
      and 35 normally resided at an altitude of 2 200 m (moderate altitude group). Body
      weight, body mass index (BMI), and waist circumference were measured in all
      subjects after a 7-day stay at Golmud (altitude of 2 800 m, baseline
      measurements). Measurements were repeated after 33-day working on Kunlun
      Mountain. In order to examine the daily rate of weight loss at high altitude,
      body weight was measured in 20 subjects from the sea level group (sea level
      subset group) each morning before breakfast for 33 d at Kunlun Mountain.
      According to guidelines established by the Lake Louise acute mountain sickness
      (AMS) consensus report, each subject completed an AMS self-report questionnaire
      two days after arriving at Kunlun Mountain. After 33-day stay at an altitude of 4
      678 m, the average weight loss for the sea level group was 10.4% (range 6.5% to
      29%), while the average for the moderate altitude group was 2.2% (-2% to 9.1%).
      The degree of weight loss (Delta weight loss) after a 33-day stay at an altitude
      of 4 678 m was significantly correlated with baseline body weight in the sea
      level group (r=0.677, P<0.01), while the correlation was absent in the moderate
      altitude group (r=0.296, P>0.05). In the sea level subset group, a significant
      weight loss was observed within 20 d, but the weight remained stable thereafter.
      AMS-score at high altitude was significantly higher in the sea level group
      (4.69+/-2.48) than that in the moderate altitude group (2.97+/-1.38), and was
      significantly correlated with baseline body weight. These results indicate that
      (1) the person with higher body weight during stay at high altitude loses more
      weight, and this is more pronounced in sea level natives when compared with that
      in moderate altitude natives; (2) heavier individuals are more likely to develop
      AMS than leaner individuals during exposure to high-altitude hypoxia.

PMID- 21170502
TI  - [Ganoderma lucidum extract protects dopaminergic neurons through inhibiting the
      production of inflammatory mediators by activated microglia].
AB  - Abundant evidence has suggested that neuroinflammation participates in the
      pathogenesis of Parkinson's disease (PD). The emerging evidence has supported
      that microglia may play key roles in the progressive neurodegeneration in PD and
      might be a promising therapeutic target. Ganoderma lucidum (GL), a traditional
      Chinese medicinal herb, has been shown potential neuroprotective effect in our
      clinical trials that lead us to speculate that it might possess potent anti
      inflammatory and immunomodulating properties. To test this hypothesis, the
      present study investigated the potential neuroprotective effect of GL and
      underlying mechanism through inhibiting microglial activation using co-cultures
      of dopaminergic neurons and microglia. The cultures of microglia or MES23.5 cells
      alone or together were treated for 24 h with lipopolysaccharide (LPS, 0.25
      MUg/mL) as a positive control, GL extracts (50-400 MUg/mL) or MES23.5 cell
      membrane fragments (150 MUg/mL) were used in treatment groups. Microglia
      activation, microglia-derived harmful factors and [(3)H]dopamine ([(3)H]DA)
      uptake of MES23.5 cells were analyzed. The results showed that microglia were
      activated by LPS and MPP(+)-treated MES23.5 cell membrane fragments,
      respectively. Meanwhile, GL extracts significantly prevented the production of
      microglia-derived proinflammatory and cytotoxic factors, including nitric oxide,
      tumor necrosis factor-alpha (TNF-alpha) and interleukin 1beta (IL-1beta), in a
      dose-dependent manner and down-regulated the TNF-alpha and IL-1beta expressions
      on mRNA level. In addition, GL extracts antagonized the reduction of [(3)H]DA
      uptake induced by MPP(+) and microglial activation. In conclusion, these results
      suggest that GL may be a promising agent for the treatment of PD through anti
      inflammation.

PMID- 21170503
TI  - [Effect of (S)-4C3HPG on brain damage in the acute stage of moderate traumatic
      brain injury model of mice and underlying mechanism].
AB  - The aim of this study is to investigate the effect of (S)-4-carboxy-3-hydroxy
      phenylglycine [(S)-4C3HPG], a mixed group I glutamate metabotropic receptor
      antagonist and a group II agonist, on impairment in a cortical impact model of
      traumatic brain injury (TBI) in mice and to elucidate the possible mechanisms.
      Mice were injected (i.p.) with saline, 1 mg/kg (S)-4C3HPG, 5 mg/kg (S)-4C3HPG and
      10 mg/kg (S)-4C3HPG (n=10 per group), respectively, at 30 min before moderate
      TBI. Neurological deficit scores, water content in injured brain and glutamate
      concentration in cerebral spinal fluid (CSF) were detected at 24 h after TBI. The
      expressions of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL
      1beta) mRNA in injured cortex were also detected by real-time RT-PCR. The results
      showed that the neurological deficits and cerebral edema were significantly
      attenuated in mice pretreated with (S)-4C3HPG (5 and 10 mg/kg respectively)
      compared with those in mice pretreated with saline. Furthermore, (S)-4C3HPG
      treatment also decreased the glutamate concentration in CSF and the expressions
      of TNF-alpha and IL-1beta mRNA remarkably in a dose-dependent manner. These
      results suggest that (S)-4C3HPG treatment attenuates cortical impact-induced
      brain injury possibly via suppression of glutamate release and inhibition of
      excessive inflammatory cytokine production. These findings highlight the
      potential benefit of glutamate metabotropic receptor ligand for preventing TBI.

PMID- 21170504
TI  - 2nd place, PREMUS best paper competition: implementing return-to-work
      interventions for workers with low-back pain--a conceptual framework to identify
      barriers and facilitators.
AB  - OBJECTIVES: Workplace-based return-to-work (RTW) interventions (programs) for
      workers with low-back pain are more effective than usual healthcare.
      Nevertheless, the implementation of such interventions usually encounters many
      barriers within healthcare systems, workplaces, and insurance systems. The aims
      of this study were to first construct a conceptual framework to identify barriers
      and facilitators before implementing RTW interventions and second validate this
      conceptual framework empirically. METHODS: We conducted a literature review to
      identify barriers and facilitators described in three domains: (i) diffusion of
      innovations; (ii) implementation of healthcare programs; and (iii) implementation
      of low-back pain clinical guidelines. A selection process was used to identify
      core dimensions. To validate this framework, we conducted a multiple case study
      with embedded levels of analysis in two regions of France. Data were collected
      through semi-structured interviews and focus groups with key participants.
      RESULTS: An initial framework was constructed with eight dimensions to be studied
      before implementation. This framework was eclectic, with different theoretical
      backgrounds. After the validation phase, some dimensions were modified, resulting
      in a revised conceptual framework that was theoretically and empirically
      grounded. CONCLUSIONS: This conceptual framework is an important contribution to
      the field of implementation science. It can be used in various settings to
      identify barriers and facilitators prior to implementing RTW interventions. In
      line with recommendations on knowledge transfer, this will enable evidence-based
      implementation strategies to be drawn up, improving intervention uptake and thus
      facilitating occupational disability prevention in low-back pain.

PMID- 21170505
TI  - Involvement of p21cip1/waf1 in the anti-proliferative effects of polyethylene
      glycol in colon carcinogenesis.
AB  - Polyethylene glycol (PEG) is a safe and effective chemopreventive agent against
      colorectal carcinogenesis in cell culture, animal models and human subjects.
      Although the precise molecular mechanism is unclear, we previously reported that
      PEG suppresses colonic epithelial proliferation. As cellular proliferation is
      driven by complex G1-S phase transition, we now characterize the role of PEG on
      cell cycle regulation. We focused our attention on the effect of PEG on the CDK
      inhibitor p21cip1/waf1, which is implicated in early colon carcinogenesis and is
      upregulated by non-steroidal anti-inflammatory drugs. These studies were done in
      the azoxymethane-treated (AOM) rat model as well as in HT-29 colon cancer cells.
      Immunohistochemical analysis revealed that while AOM decreased the p21 expression
      (75%, p<0.01) in the premalignant colonic mucosa, PEG induced p21 levels back to
      normal. These findings paralleled a decreased BrdUrd incorporation (78%, p<0.001)
      and hypophosphorylated retinoblastoma protein (Rb; by 47%) signifying PEG's
      antiproliferative activity. Furthermore, in HT-29 cells, PEG decreased
      proliferation as measured by PCNA (68% reduction), increased p21 expression (2.3
      fold), induced cell cycle arrest during G0/G1 phase (45% reduction in S phase
      cells) and inhibited the phosphorylation of Rb (by 52% compared to untreated).
      PEG caused greater than a 2-fold induction of protein and mRNA level of
      p21cip1/waf1 in HT-29 cells. These results demonstrate for the first time that
      PEG is involved in p21 regulation concomitant with G1S phase cell cycle arrest
      and it is through these effects that it can exert its anti-proliferative and
      hence chemopreventive role.

PMID- 21170506
TI  - Chrysin-induced apoptosis is mediated through p38 and Bax activation in B16-F1
      and A375 melanoma cells.
AB  - Chrysin (5,7-dihydroxyflavone) is a natural and biologically active compound
      extracted from honey, plants and propolis. It possesses anti-inflammatory
      activity, anti-oxidant properties and promotes cell death by perturbing cell
      cycle progression. In this study, our attention focused on the possible role that
      chrysin may have as a potential anti-cancer agent, and we tested its biological
      activity in murine and human melanoma cell lines (B16-F1 and A375). This study
      demonstrated that chrysin reduced melanoma cell proliferation and induced cell
      differentiation in both human and murine melanoma cells through synthesis
      increase and intracellular accumulation of protoporphirin IX (PpIX). Furthermore,
      following treatments with chrysin an increase in the expression of
      porphobilinogen deaminase (PBG-D) was noted. This study demontrated also that
      chrysin induces cell death in human and murine melanoma cells through caspase
      dependent mechanisms, involving down-regulation of ERK 1/2, and activation of p38
      MAP kinases. Induction of cell death may be a promising therapeutic approach in
      cancer therapy. Our results suggest that chrysin may be considered a potential
      candidate for both cancer prevention and treatment.

PMID- 21170507
TI  - Thiazolidinediones/PPARgamma agonists and fatty acid synthase inhibitors as an
      experimental combination therapy for prostate cancer.
AB  - The prostate cancer (PCa) cell lines LNCaP, PC-3, and DU-145 express peroxisome
      proliferator-activated receptor gamma (PPARgamma) but its role in PCa is unclear.
      Thiazolidinediones (TZDs), a family of PPARgamma activators and type 2 anti
      diabetic drugs, exhibit anti-tumor apoptotic effects in human PCa cell lines.
      Likewise, pharmacological inhibitors of fatty acid synthase (FASN), a metabolic
      enzyme highly expressed in PCa, induce apoptosis in prostate and other cancer
      cells. Here, we show positive correlation between PPARgamma and FASN protein in
      PCa cell lines and synergism between TZDs and FASN blockers in PCa cell viability
      reduction and apoptosis induction. Combined TZDs/FASN has enhanced anti-tumor
      properties in both androgen-dependent LNCaP and androgen-independent PC-3 and DU
      145 cells when compared with single drug exposure. Low concentrations (5-10 MUM)
      of the TZD drug rosiglitazone failed to alter cell viability but, paradoxically,
      upregulated lipogenic genes [PPARgamma, FASN, sterol regulatory element binding
      protein-1c (SREBP-1c) and acetyl-Co A carboxylase-1 (ACC1)], which diminish the
      apoptotic effects of rosiglitazone. The mean IC50 in all cell lines was 45 +/- 2
      MUM for rosiglitazone compared with significantly lower 5 +/- 1 MUM for
      rosiglitazone plus the FASN blocker cerulenin, and 10.2 +/- 2 MUM for
      rosiglitazone plus the cerulenin synthetic analog C75. The IC50 for the combined
      rosiglitazone and FASN blockers contrasts with the relatively higher IC50 for
      rosiglitazone (45 +/- 2 MUM), the TZD drug troglitazone (13 +/- 2 MUM), cerulenin
      (32 +/- 1 MUM), or C75 (26 +/- 3 MUM) when these drugs were used alone. In
      summary, this study shows proof-of-principle for combining FASN blockers and TZDs
      for PCa treatment.

PMID- 21170508
TI  - Berberine sensitizes TRAIL-induced apoptosis through proteasome-mediated
      downregulation of c-FLIP and Mcl-1 proteins.
AB  - Berberine (BBR) is an isoquinoline alkaloid which has a wide spectrum of clinical
      applications including anti-tumor, anti-microbial and anti-inflammatory
      activities. In this study, we showed that co-treatment with subtoxic doses of BBR
      and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induced
      apoptosis in human renal cancer cells, Caki cells, but not in normal tubular
      kidney cells. Treatment of Caki cells with BBR resulted in downregulation of c
      FLIP and Mcl-1 proteins in a dose-dependent manner. The BBR-induced
      downregulation of c-FLIP and Mcl-1 proteins were involved in proteasome dependent
      pathways, which was confirmed by the result that pre-treatment with the
      proteasome inhibitor MG132 inhibited berberine-induced downregulation of the c
      FLIP and Mcl-1 proteins. Pretreatment with N-acetyl-L-cysteine (NAC)
      significantly inhibited the cell death induced by the combined treatment with BBR
      and TRAIL as well as recovered the expression levels of c-FLIP and Mcl-1
      downregulated by treatment with BBR. These results suggested that BBR-stimulated
      TRAIL-induced apoptosis is dependent on the generation of reactive oxygen species
      through the downregulation of c-FLIP and Mcl-1 proteins. In conclusion, this
      study demonstrates that BBR enhances TRAIL-induced apoptosis in human renal
      cancer cells by ROS-mediated c-FLIP and Mcl-1 down-regulation.

PMID- 21170509
TI  - HDAC inhibitors downregulate MRP2 expression in multidrug resistant cancer cells:
      implication for chemosensitization.
AB  - Although histone deacetylase (HDAC) inhibitors are emerging as a promising class
      of cancer chemotherapeutic agents, their effects on multidrug resistance (MDR)
      are poorly understood. In this study, we investigated whether HDAC inhibitors
      overcome MDR phenotype. HDAC inhibitors suppress the growth of both MDR positive
      cancer cells KBV20C and its parental cells KB with similar potencies. In
      parallel, histone acetylation and p21WAF1 expression by the HDAC inhibitors were
      similarly increased in both cell types, indicating that these HDAC inhibitors are
      poor substrates of ABC drug transporters and effective in MDR cancer cells. In
      addition, multidrug resistance protein 2 (MRP2) expression is selectively
      attenuated by HDAC inhibitors, especially SAHA and TSA, in KBV20C cells, whereas
      MDR1 and BCRP expressions are not affected. This downregulation of MRP2
      contributes to increase in paclitaxel-induced G2/M arrest and apoptosis, which
      might be due to intracellular accumulation of paclitaxel. Collectively, our data
      provide a molecular rationale for the application of HDAC inhibitors to overcome
      MDR in cancer cells.

PMID- 21170510
TI  - [Intraluminal surgical procedures for glottic enlargement in bilateral vocal fold
      paralysis in adduction].
AB  - Bilateral vocal fold paralysis with paramedian position of the vocal chords can
      result from iatrogenic or traumatic nerve injuries, neurologic disorders and
      extralaryngeal malignancies and usually causes significant shortness of breath
      while the voice is only slightly affected. Only about 10% of the affected
      patients tolerate the narrowed airway caused by bilateral vocal fold paralysis in
      adduction, so most patients are candidates for a surgical intervention. Today, a
      range of intraluminal surgical procedures for enlargement of the glottis in
      bilateral vocal fold paralysis have been described which intend to avoid or
      supersede tracheostomy and which have replaced time-consuming external approaches
      to the glottis. This report provides an overview of the most important
      intraluminal surgical procedures for bilateral vocal fold paralysis in adduction
      and comments in detail on indications, surgical techniques, advantages and
      potential complications of the presented procedures for temporary or definitive
      enlargement of the glottis.

PMID- 21170511
TI  - [Symptom management of pain and breathlessness].
AB  - Pain and breathlessness are common symptoms in advanced disease. Pain should be
      treated with a combination of non-opioids and opioids. Coanalgesics play an
      important role in the treatment of neuropathic pain. Side-effects of opioids
      should be treated prophylactically but can make opioid rotation necessary.
      Management of breathlessness needs a combination of non-pharmacological and
      pharmacological measures. Fans and rollators showed to be effective in relieving
      breathlessness. Opioids are the drugs of choice for breathlessness. The efficacy
      of benzodiazepines could not be confirmed, they should only be used as second
      line therapy. Also, oxygen should only be given regularly after an individual
      test.

PMID- 21170512
TI  - [Definitions and goals in palliative medicine].
AB  - Especially in the last 15 years Palliative Care and Palliative Medicine in
      Germany have increasingly attracted professional and public attention and made
      remarkable progress. One of the characteristics of Palliative Care in Germany is
      the differentiation of palliative care from hospice care. Under different
      viewpoints structure, target groups and aims of Palliative Care have been under
      discussion in the last 30 years, which made an impact on different forms in the
      provision of care. Palliative therapy should be distinguished from supportive
      care and palliative medicine. The revised WHO-definition of Palliative Care
      broadened the aspects of care in a comprehensive and more holistic understanding
      of the social, emotional and spiritual needs of patients and their families,
      including bereavement; and, finally, interdisciplinary and team working issues.
      It is important to differentiate the palliative care approach from general and
      specialized palliative care provision for patients with incurable progressive
      illness and in old age. In Germany 10-12% of all dying patients per year are in
      need of a specialized palliative care service. The growth in the group of the
      "very old" will be an important challenge for palliative care in the near future.

PMID- 21170514
TI  - Fecundability among women with type 1 and type 2 diabetes in the Norwegian Mother
      and Child Cohort Study.
AB  - AIMS/HYPOTHESIS: We assessed the effects of type 1 diabetes and type 2 diabetes
      on fecundability (as manifest by increased time-to-pregnancy [TTP]) in a large
      cohort of pregnant women. METHODS: This study is based on the Norwegian Mother
      and Child Cohort Study. Members of this large cohort were enrolled early in
      pregnancy and asked about TTP and other factors. Among the 58,004 women included
      in the analysis, we identified 221 cases of type 1 diabetes and 88 cases of type
      2 diabetes using the Medical Birth Registry of Norway. A logistic analogue of the
      proportional probability model, a Cox-like discrete-time model, was used to
      compute fecundability odds ratios (FORs) and 95% CI for type 1 diabetes and type
      2 diabetes, adjusted for maternal age and prepregnancy BMI. RESULTS: Compared
      with non-diabetic women, the adjusted FOR for women with type 1 diabetes was 0.76
      (95% CI 0.64-0.89) and the adjusted FOR for women with type 2 diabetes was 0.64
      (95% CI 0.48-0.84). These FORs did not change substantively and remained
      statistically significant after excluding women with irregular menstrual cycles
      and accounting for cycle length. CONCLUSIONS/INTERPRETATION: The results from the
      present study provide evidence of substantially decreased fecundability for women
      with type 1 and type 2 diabetes, even among those with a normal menstrual cycle.

PMID- 21170515
TI  - Adolescents who are frequent attenders to primary care: contribution of
      psychosocial factors.
AB  - BACKGROUND: Frequent attendance to primary care services has shown an association
      with psychosocial factors in adult and child populations. Little is known about
      the psychosocial correlates of attendance in adolescents. AIMS OF THE STUDY: To
      study the contribution of psychosocial factors to frequent primary care
      attendance in a community sample of young British people. METHOD: The method used
      was a cross-sectional survey of 1,251 secondary school pupils, using self-report
      questionnaires for socio-demographic, physical and psychological health data.
      RESULTS: A total of 1,116 pupils [mean age 13.51 years (SD 1.5), 52% female]
      completed questionnaires and provided information about contact with their
      general practitioner (GP) in the previous year; 30% were frequent attenders (>=4
      appointments). Frequent attenders were significantly younger; they were more
      likely to come from lower socioeconomic backgrounds, report significantly more
      past and current physical problems, have more hospital visits in the previous
      year, have more recent intense somatic symptoms made worse by stress and causing
      impairment, and have more days off school. Frequent attendance was also
      significantly associated with the presence of emotional symptoms and a history of
      mental health consultations. Logistic regression analysis identified seeing a
      hospital doctor, current illness, having days off school, a history of mental
      health consultations and younger age as independent predictors of frequent
      attendance. CONCLUSION: In addition to physical health problems, social factors
      and psychiatric difficulty are linked to and require attention in young people
      who are frequent attenders at primary care health services.

PMID- 21170516
TI  - [Nerve compression syndrome of the shoulder : Arthroscopic decompression
      procedures].
AB  - Several nerve compression syndromes have been described in the literature
      involving compression of the axillary nerve in the quadrangular space and most
      importantly compression of the suprascapular nerve in the suprascapular as well
      as the spinoglenoid notch. This article describes the arthroscopic techniques of
      nerve decompression around the shoulder.

PMID- 21170513
TI  - Emerging therapeutic approaches in the management of retinal angiogenesis and
      edema.
AB  - Conditions resulting in retinal angiogenesis and edema (exudative age-related
      macular degeneration, diabetic retinopathy, retinal vein occlusion and
      retinopathy of prematurity) are major causes of visual impairment, with
      significant impact on quality of life. There has been increasing clinical usage
      of anti-vascular endothelial growth factor (anti-VEGF) agents to stop retinal
      angiogenesis and resolve intraretinal fluid arising from these conditions.
      However, anti-VEGFs have not been completely successful in curing these
      conditions, and a range of emerging treatments aimed at supplementing or
      competing with anti-VEGF agents are being developed. We will discuss the proposed
      merits these emerging agents bring to the treatment arsenal and how they compare
      with anti-VEGFs with regards to therapeutic activity, potency, specificity and
      safety. This review will also highlight recent pre-clinical research findings and
      suggest where future research might be directed.

PMID- 21170517
TI  - [Arthroscopic stabilization of acute acromioclavicular joint dislocation].
AB  - During the past few years arthroscopic and minimal invasive techniques for
      stabilization of acromioclavicular (AC) joint dislocations have gained increasing
      interest. Well established procedures for open surgery were modified and
      implemented to attain an arthroscopic level. Furthermore implants were developed
      which enable these reconstructive techniques to be performed arthroscopically
      without the disadvantages of open procedures. The short to mid-term results
      described so far concerning the clinical and radiological outcome of arthroscopic
      stabilization techniques show an at least equal outcome to those presented in
      open surgery.

PMID- 21170519
TI  - Electrochemistry-mass spectrometry for mechanistic studies and simulation of
      oxidation processes in the environment.
AB  - Electrochemistry (EC) coupled to mass spectrometry (MS) has already been
      successfully applied to metabolism research for pharmaceutical applications,
      especially for the oxidation behaviour of drug substances. Xenobiotics (chemicals
      in the environment) also undergo various conversions; some of which are oxidative
      reactions. Therefore, EC-MS might be a suitable tool for the investigation of
      oxidative behaviour of xenobiotics. A further evaluation of this approach to
      environmental research is presented in the present paper using sulfonamide
      antibiotics. The results with sulfadiazine showed that EC-MS is a powerful tool
      for the elucidation of the oxidative degradation mechanism within a short time
      period. In addition, it was demonstrated that EC-MS can be used as a fast and
      easy method to model the chemical binding of xenobiotics to soil. The reaction of
      sulfadiazine with catechol, as a model substance for organic matter in soil, led
      to the expected chemical structure. Finally, by using EC-MS a first indication
      was obtained of the persistence of a component under chemical oxidation
      conditions for the comparison of the oxidative stability of different classes of
      xenobiotics. Overall, using just a few examples, the study demonstrates that EC
      MS can be applied as a versatile tool for mechanistic studies of oxidative
      degradation pathways of xenobiotics and their possible interaction with soil
      organic matter as well as their oxidative stability in the environment. Further
      studies are needed to evaluate the full range of possibilities of the application
      of EC-MS in environmental research.

PMID- 21170518
TI  - The cannabinergic system is implicated in the upregulation of central NGF protein
      by psychotropic drugs.
AB  - RATIONALE: Studies on the regulation of nerve growth factor (NGF) levels by
      psychotropics are limited in scope and the mechanism(s) remain elusive which
      merit further elucidation. OBJECTIVES: We aimed to perform a more comprehensive
      investigation on the possible effects of pharmacologically heterogeneous groups
      of psychotropic drugs on NGF contents in the brain regions involved in the
      modulation of emotions. As a mechanistic approach, we looked at the role of the
      cannabinergic system which is linked to depression and/or antidepressant effect
      and appears to interact with neurotrophin signaling. METHODS: Following
      psychotropic treatment, NGF or endocannabinoid (eCB) contents were quantified by
      Bio-Rad protein assay and isotope-dilution liquid chromatography/mass
      spectrometry, respectively. In case of any significant change, the effects of
      pretreatment with the CB(1) receptor neutral antagonist AM4113 were investigated.
      RESULTS: Single injection of nortriptyline, isocarboxazid, citalopram, diazepam,
      risperidone (2.5, 5, and 10 mg/kg, each), and fluphenazine (0.25, 0.5, and 1
      mg/kg) into rats did not alter NGF or eCB contents. Following 4-week treatment,
      all drugs except diazepam elevated NGF or eCB levels in dose-dependent and brain
      region-specific fashion. Pretreatment with the highest dose of AM4113 (5.6 mg/kg)
      prevented psychotropic-induced NGF or eCB elevation. AM4113 had no effect by
      itself. CONCLUSIONS: The cannabinergic system is implicated in the mechanisms of
      action of certain psychotropic drugs including the upregulation of brain NGF
      levels. This provides a better understanding of the pathophysiological mechanisms
      underlying neuropsychiatric disorders, leading to novel drug design.

PMID- 21170521
TI  - The 2010 Chemistry Nobel Prize to R.F. Heck, E. Negishi, and A. Suzuki for
      palladium-catalyzed cross-coupling reactions.

PMID- 21170520
TI  - Simultaneous quantification and qualification of synacthen in plasma.
AB  - Tetracosactide (Synacthen), a synthetic analogue of adrenocorticotropic hormone
      (ACTH), can be used as a doping agent to increase the secretion of
      glucocorticoids by adrenal glands. The only published method for anti-doping
      control of this drug in plasma relies on purification by immunoaffinity
      chromatography and LC/MS/MS analysis. Its limit of detection is 300 pg/mL, which
      corresponds to the peak value observed 12 h after 1 mg Synacthen IM
      administration. We report here a more sensitive method based on preparation of
      plasma by cation exchange chromatography and solid-phase extraction and analysis
      by LC/MS/MS with positive-mode electrospray ionization using 7-38 ACTH as
      internal standard. Identification of Synacthen was performed using two product
      ions, m/z 671.5 and m/z 223.0, from the parent [M + 5H](5+) ion, m/z 587.4. The
      recovery was estimated at 70%. A linear calibration curve was obtained from 25 to
      600 pg/mL (R2 > 0.99). The lower limit of detection was 8 pg/mL (S/N > 3). The
      lower limit of quantification was 15 pg/mL (S/N > 10; CV% < 20%). The performance
      of the method was illustrated by an 8-h kinetic analysis of plasma samples from
      nine subjects submitted to IM injections of either Synacthen(r) (five subjects)
      or Synacthen(r) Depot, the slow-release form of the drug (four subjects).
      Concentrations of Synacthen between 16 and 310 pg/mL were observed. A sensitive
      method for quantitation of Synacthen in plasma is proposed for anti-doping
      control analyses.

PMID- 21170522
TI  - Development of an analytical protocol for a fast, sensitive and specific protein
      recognition in paintings by enzyme-linked immunosorbent assay (ELISA).
AB  - Enzyme-linked immunosorbent assay (ELISA) analysis of proteins offers a
      particularly promising approach for investigations in cultural heritage on
      account of its appreciated properties of being highly specific, sensitive,
      relatively fast, and cost-affordable with respect to other conventional
      techniques. In spite of that, it has never been fully exploited for routine
      analyses of painting materials in consideration of several analytical issues that
      inhibited its diffusion in conservation science: limited sample dimensions,
      decrease of binder solubility and reduced availability of antibody bonding sites
      occurring with protein degradation. In this study, an ELISA analytical protocol
      suited for the identification of aged denatured proteins in ancient painting
      micro-samples has been developed. We focused on the detection of bovine beta
      casein and chicken ovalbumin as markers of bovine milk (or casein) and chicken
      albumen, respectively. A systematic experimentation of the ELISA protocol has
      been carried out on mock-ups of mural and easel painting prepared with 13
      different pigments to assess limits and strengths of the method when applied for
      the identification of proteins in presence of a predominant inorganic matrix. The
      analytical procedure has been optimized with respect to protein extraction,
      antibodies' concentrations, incubation time and temperature; it allows the
      detection of the investigated proteins with sensitivity down to nanograms. The
      optimized protocol was then tested on artificially aged painting models.
      Analytical results were very encouraging and demonstrated that ELISA allows for
      protein analysis also in degraded painting samples. To address the feasibility of
      the developed ELISA methodology, we positively investigated real painting samples
      and results have been cross-validated by gas chromatography-mass spectrometry.

PMID- 21170523
TI  - Variable MR imaging appearances of focal nodular hyperplasia in pediatric cancer
      patients.
AB  - BACKGROUND: Focal nodular hyperplasia (FNH) is rare in the general pediatric
      population but is increasingly found in treated pediatric cancer patients. FNH
      can be incidentally found on CT and MRI and can be misdiagnosed as liver
      metastasis in patients with an oncological history. OBJECTIVE: To describe the MR
      imaging findings of FNH in pediatric cancer patients. MATERIALS AND METHODS: Ten
      children who had been treated for a primary malignancy and who were diagnosed
      with FNH from 2003 to 2010 were identified from a search for FNH in our pathology
      and radiology databases. Patients were included if they were treated for a
      primary malignancy and had undergone MR imaging of the liver including T1
      weighted, T2-weighted and dynamic contrast-enhanced T1-weighted sequences.
      RESULTS: FNH from all patients (n=10) demonstrated typical homogeneous arterial
      enhancement on MRI. The FNH was often multiple and small (7/10 patients), lacking
      a central scar, with variable imaging characteristics including signal
      hyperintensity on both T1- and T2-weighted images (4/10 patients), especially in
      the setting of hepatic hemosiderosis. CONCLUSION: FNH has a variable MR
      appearance in pediatric cancer patients and should be considered in the
      differential diagnosis of hypervascular liver lesions.

PMID- 21170524
TI  - Upright MRI measurement of mechanical axis and frontal plane alignment as a new
      technique: a comparative study with weight bearing full length radiographs.
AB  - OBJECTIVE: The purpose of this prospective study was to investigate the
      practicality, accuracy, and reliability of upright MR imaging as a new radiation
      free technique for the measurement of mechanical axis. METHODS: We used upright
      MRI in 15 consecutive patients (30 limbs, 44.7 +/- 20.6 years old) to measure
      mechanical axis deviation (MAD), hip-knee-ankle (HKA) angle, leg length, and all
      remaining angles of the frontal plane alignment according to Paley (mLPFA, mLDTA,
      mMPTA, mLDTA, JLCA). The measurements were compared to weight bearing full length
      radiographs, which are considered to be the standard of reference for planning
      corrective surgery. FDA-approved medical planning software (MediCAD) was used for
      the above measurements. Intra- and inter-observer reproducibility using mean
      absolute differences was also calculated for both methods. RESULTS: The
      correlation coefficient between angles determined with upright MRI and weight
      bearing full length radiographs was high for mLPFA, mLDTA, mMPTA, mLDTA, and the
      HKA angle (r > 0.70). Mean interobserver and intraobserver agreements for upright
      MRI were also very high (r > 0.89). The leg length and the MAD were significantly
      underestimated by MRI (-3.2 +/- 2.2 cm, p < 0.001 and -6.2 +/- 4.4 mm, p = 0.006,
      respectively). CONCLUSIONS: With the exception of underestimation of leg length
      and MAD, upright MR imaging measurements of the frontal plane angles are precise
      and produce reliable, reproducible results.

PMID- 21170527
TI  - Landscape connectivity shapes the spread pattern of the rice water weevil: a case
      study from Zhejiang, China.
AB  - The spread of invasive species is a complex ecological process that is affected
      by both the biology of the species and the spatial structure of a landscape. The
      rice water weevil (Lissorhoptrus oryzophilus Kuschel), a notorious crop pest
      found in many parts of the world, is one of the most devastating invasive species
      in China, and has caused enormous economic losses and ecological damage. Little
      is known, however, as to how habitat and landscape features affect the spatial
      spread of this pest. Thus, the main goal of this study was to investigate the
      relationship between the observed spread pattern of L. oryzophilus and landscape
      structural factors in Zhejiang Province, China between 1993 and 2001. We
      quantified the invasive spread of the weevil in terms of both the proportion of
      infected area and spread distance each year as well as landscape structure and
      connectivity of rice paddies with landscape metrics. Our results showed that the
      spread of L. oryzophilus took place primarily in the southwest-northeast
      direction along coastal areas at a speed of about 36 km per year. The composition
      and spatial arrangement of landscape elements were key determinants of this
      unique spread pattern. In particular, the connectivity of early rice paddies was
      crucial for the invasive spread while other factors such as meteorological and
      geographical conditions may also have been relevant. To control the spread of the
      pest, we propose four management measures: (1) to implement a landscape-level
      planning scheme of cropping systems to minimize habitat area and connectivity for
      the pest, (2) to reduce the source populations at a local scale using integrated
      control methods, (3) to monitor and report invasive spread in a timely manner,
      and (4) to strengthen the quarantine system. To be most effective, all four
      management measures need to be implemented together through an integrated, multi
      scaled approach.

PMID- 21170526
TI  - Renal uptake of different radiolabelled peptides is mediated by megalin: SPECT
      and biodistribution studies in megalin-deficient mice.
AB  - PURPOSE: Radiolabelled peptides used for peptide receptor radionuclide therapy
      are excreted mainly via the kidneys and are partly reabsorbed and retained in the
      proximal tubular cells. The resulting high renal radiation dose can cause
      nephrotoxicity, limiting the maximum activity dose and the effectiveness of
      peptide receptor radionuclide therapy. The mechanisms of kidney reabsorption of
      these peptides are incompletely understood, but the scavenger receptor megalin
      has been shown to play a role in the reabsorption of (111)In-octreotide. In this
      study, the role of megalin in the renal reabsorption of various relevant
      radiolabelled peptides was investigated. METHODS: Groups of kidney-specific
      megalin-deficient mice and wild-type mice were injected with (111)In-labelled
      somatostatin, exendin, neurotensin or minigastrin analogues. Single photon
      emission computed tomographic (SPECT) images of the kidneys were acquired and
      analysed quantitatively, or the animals were killed 3 h after injection and the
      activity concentration in the kidneys was measured. RESULTS: Megalin-deficient
      mice showed significantly lower uptake of all studied radiolabelled peptides in
      the kidneys, ranging from 22% ((111)In-octreotide) to 65% ((111)In-exendin) of
      uptake in wild-type kidneys. Quantitative analysis of renal uptake by SPECT and
      ex vivo measurements showed a very good correlation. CONCLUSION: Megalin is
      involved in the renal reabsorption of radiolabelled octreotide, octreotate,
      exendin, neurotensin and minigastrin. This knowledge may help in the design of
      strategies to reduce this reabsorption and the resulting nephrotoxicity in
      peptide receptor radionuclide therapy, enabling more effective therapy. Small
      animal SPECT is an accurate tool, allowing in vivo quantification of renal uptake
      and serial measurements in individual mice.

PMID- 21170525
TI  - In vivo imaging of immune cell trafficking in cancer.
AB  - Tumour establishment, progression and regression can be studied in vivo using an
      array of imaging techniques ranging from MRI to nuclear-based and optical
      techniques that highlight the intrinsic behaviour of different cell populations
      in the physiological context. Clinical in vivo imaging techniques and preclinical
      specific approaches have been used to study, both at the macroscopic and
      microscopic level, tumour cells, their proliferation, metastasisation, death and
      interaction with the environment and with the immune system. Fluorescent,
      radioactive or paramagnetic markers were used in direct protocols to label the
      specific cell population and reporter genes were used for genetic, indirect
      labelling protocols to track the fate of a given cell subpopulation in vivo.
      Different protocols have been proposed to in vivo study the interaction between
      immune cells and tumours by different imaging techniques (intravital and whole
      body imaging). In particular in this review we report several examples dealing
      with dendritic cells, T lymphocytes and macrophages specifically labelled for
      different imaging procedures both for the study of their physiological function
      and in the context of anti-neoplastic immunotherapies in the attempt to exploit
      imaging-derived information to improve and optimise anti-neoplastic immune-based
      treatments.

PMID- 21170528
TI  - Sclerotic vertebral metastases: pain palliation using percutaneous image-guided
      cryoablation.
AB  - Cryoablative therapies have been proposed to palliate pain from soft-tissue or
      osteolytic bone tumors. A case of a patient with painful thoracic and sacral
      spine sclerotic metastases successfully treated by image-guided percutaneous
      cryoablation with the aid of insulation techniques and thermosensors is reported
      in this case report.

PMID- 21170529
TI  - Acute abdominal pain after retrievable inferior vena cava filter insertion: case
      report of caval perforation by an option filter.
AB  - Symptomatic caval injury is rare after inferior vena cava (IVC) filter insertion.
      A 39-year-old woman developed acute abdominal pain after uneventful placement of
      a retrievable Option IVC Filter (Angiotech Pharmaceuticals, Vancouver, British
      Columbia, Canada). Two days after placement, computed tomography showed a right
      sided retroperitoneal hematoma, and three-dimensional C-arm rotational venography
      confirmed limb penetration beyond the caval wall. This is the first report of
      this complication despite two recent studies highlighting the safety profile of
      this relatively new filter.

PMID- 21170530
TI  - Adrenal radiofrequency ablation in swine: change in blood pressure and
      histopathologic analysis.
AB  - PURPOSE: To evaluate changes in blood pressure during adrenal radiofrequency
      ablation (RFA) and analyze histopathologic outcomes in swine adrenal glands.
      MATERIALS AND METHODS: Animal Care Committee approval was obtained for this
      study. After laparotomy, a single adrenal gland was ablated from each of six
      animals (six RF sessions total). An internally cooled-tip RF electrode was placed
      along the long axis of the adrenal gland, and RF energy was applied for 10 min in
      each adrenal gland. Blood pressure and heart rate were monitored, and serum
      epinephrine, norepinephrine, and cortisol levels were measured before, during,
      and after RFA. Histological study was performed using hematoxylin-eosin staining.
      RESULTS: RFA was completed according to a planned protocol in all adrenal glands.
      Blood pressure increased to >200 mm Hg after an increase in heart rate during all
      six RF sessions. Mean serum epinephrine and norepinephrine levels increased
      significantly during RFA. However, mean cortisol levels showed no significant
      increase during or after RFA. Histological studies showed adrenal cell necrosis
      throughout the adrenal glands in all but one pig, with the mean necrosis rate
      being 99.1 +/- 2.3% (range 94.3-100%). CONCLUSION: Adrenal RFA causes extensive
      adrenal cell damage and causes catecholamine-induced hypertension.

PMID- 21170531
TI  - Detachment of introducer sheath radiopaque marker during retrieval of G2 filter.

PMID- 21170532
TI  - Embolization of an internal iliac artery aneurysm after image-guided direct
      puncture.
AB  - OBJECTIVE: To evaluate the feasibility, safety, and efficacy of embolization of
      internal iliac artery aneurysm (IIAA) after percutaneous direct puncture under
      (cone-beam) computed tomography (CT) guidance. METHODS: A retrospective case
      series of three patients, in whom IIAA not accessible by way of the transarterial
      route, was reviewed. CT-guided puncture of the IIAA sac was performed in one
      patient. Two patients underwent puncture of the IIAA under cone-beam CT guidance.
      RESULTS: Access to the IIAA sac was successful in all three patients. In two of
      the three patients, the posterior and/or anterior division was first embolized
      using platinum microcoils. The aneurysm sac was embolized with thrombin in one
      patient and with a mixture of glue and Lipiodol in two patients. No complications
      were seen. On follow-up CT, no opacification of the aneurysm sac was seen. The
      volume of one IIAA remained stable at follow-up, and the remaining two IIAAs
      decreased in size. CONCLUSION: Embolization of IIAA after direct percutaneous
      puncture under cone-beam CT/CT-guidance is feasible and safe and results in good
      short-term outcome.

PMID- 21170533
TI  - Beta cells under attack: toward a better understanding of type 1 diabetes
      immunopathology.

PMID- 21170534
TI  - Functional characterization of Vibrio alginolyticus twin-arginine translocation
      system: its roles in biofilm formation, extracellular protease activity, and
      virulence towards fish.
AB  - The bacterial twin-arginine translocation (Tat) system contributes to translocate
      folded proteins and plays pleiotropic roles in growth, motility, and the
      secretion of some virulent factors. In this study, the authors identified the Tat
      gene cluster in fish pathogen Vibrio alginolyticus and explored its roles in
      pathogenesis toward fish. Vibrio alginolyticus Tat mutants showed growth
      deficiency in TMAO medium, while the complement strain restored the ability to
      grow in the medium, demonstrating the conservative function of the Tat system in
      translocation of redox enzymes or cofactors in this bacterium. In V.
      alginolyticus, deletion of the tatABC genes led to a drastic decrease in biofilm
      biogenesis. Interestingly, the secretion of extracellular protease Asp, an
      established exotoxin of the bacterium, was significantly decreased in the TatC
      mutant, suggesting that TatC might play a part in the production of virulence
      factors in the bacterium. Furthermore, the Tat mutants displayed attenuated
      virulence toward the fish model and EPC cells. These findings suggest that the
      Tat secretion related to the extracellular protease activity as well as virulence
      in V. alginolyticus provided new insights into the pathogenesis of vibriosis in
      fish.

PMID- 21170535
TI  - [Update from the soft tissue tumour registry in Jena].
AB  - The Jena Institute of Pathology has been serving as a consultation and reference
      center for soft tissue tumors in Germany since 1978. The present study provides
      an overview of the clinicopathological data from a two-year period and an update
      on diagnostics and research. Retrospectively, 7043 cases sent to the institute in
      the years 2006 and 2007 were analyzed. The majority of cases (>77.7%) were soft
      tissue tumors, of which 49% were categorized as malignant, 11.4% as intermediate,
      35% as benign and 4.6% as tumors of uncertain biological potential. Neoplasms
      with fibroblastic differentiation were the most frequent. The mean age of
      patients with a sarcoma was 63 years. The molecular pathological analysis of soft
      tissue tumors has attained a major role in diagnosis. This is further advanced at
      the Jena institute in the context of a German Federal Ministry of Education and
      Research (BMBF) project for molecular sarcoma diagnosis with the aim of
      developing and validating DNA probes for in situ hybridization detection of
      translocations and their associated chromosomal breaks on the one hand, and DNA
      chips for the detection of fusion transcripts on the other. Research projects
      relate to the analysis of specific biomarkers in large tumor collectives and the
      pathomechanisms in several sarcoma entities.

PMID- 21170536
TI  - Chemical priming for spinal cord injury: a review of the literature. Part I
      factors involved.
AB  - INTRODUCTION: There are significant differences between the propensity of neural
      regeneration between the central and peripheral nervous systems. MATERIALS AND
      METHODS: Following a review of the literature, we describe the role of growth
      factors, guiding factors, and neurite outgrowth inhibitors in the physiology and
      development of the nervous system as well as the pathophysiology of the spinal
      cord. We also detail their therapeutic role as well as those of other chemical
      substances that have recently been found to modify regrowth following cord
      injury. CONCLUSIONS: Multiple factors appear to have promising futures for the
      possibility of improving spinal cord injury following injury.

PMID- 21170537
TI  - Body weight and energy homeostasis was not affected in C57BL/6 mice fed high whey
      protein or leucine-supplemented low-fat diets.
AB  - BACKGROUND: Leucine is suggested to act as nutrient signal of high-protein diets
      regulating pathways associated with an alleviation of metabolic syndrome
      parameters. However, the subject remains controversial. AIM OF THE STUDY: The aim
      of this study was to assess and to compare the effects of high-protein diets with
      dietary leucine supplementation in mice, particularly on energy homeostasis, body
      composition, and expression of uncoupling protein (UCP), which are suggested to
      decrease food energy efficiency. METHODS: Male C57BL/6 mice were exposed for 14
      weeks to semi-synthetic diets containing either 20% (adequate protein content,
      AP) or 50% whey protein (high-protein content, HP). A third group was fed the AP
      diet supplemented with L-leucine (AP + L) corresponding to the leucine content of
      the HP diet. The total fat content was 5% (w/w). RESULTS: Body weight gain, body
      composition, energy expenditure, and protein expression of UCP1 in brown adipose
      tissue, and UCP3 in skeletal muscle were not different between groups. In HP-fed
      mice, a stronger increase in blood glucose levels was detected during glucose
      tolerance tests compared to AP and AP + L, whereas plasma insulin was similar in
      all groups. Leucine supplementation did not affect glucose tolerance. Plasma
      cholesterol was significantly decreased in HP and AP + L when compared to AP.
      Plasma triglyceride concentrations were increased twofold in HP-fed mice when
      compared to AP + L and AP groups. Liver and skeletal muscle triglyceride and
      glycogen concentrations were similar in all groups. Postabsorptive plasma
      concentrations of branched-chain amino acids were not significantly increased
      after exposure to HP and AP + L diets, whereas those of lysine were decreased in
      HP and AP + L mice when compared to AP (P < 0.001). Plasma methionine
      concentrations were lower after HP intake when compared to AP and AP + L (P <
      0.05). CONCLUSIONS: We suggest that an exposure of mice to HP diets or a
      corresponding leucine supplementation has no significant effect on energy
      homeostasis and UCP expression compared with AP diets when feeding a low-fat
      diet. The use of high-quality whey protein might at least in part explain the
      results obtained.

PMID- 21170538
TI  - The pathological process underlying Alzheimer's disease in individuals under
      thirty.
AB  - Brains of 42 individuals between the ages of 4 and 29 were examined with
      antibodies (AT8, 4G8) and silver stains for the presence of intraneuronal and
      extracellular protein aggregates associated with Alzheimer's disease. Thirty
      eight of 42 (38/42) cases displayed abnormally phosphorylated tau protein
      (pretangle material) in nerve cells or in portions of their cellular processes,
      and 41/42 individuals showed no extracellular amyloid-beta protein deposition or
      neuritic plaques-an individual with Down syndrome was the only exception. In
      16/42 cases abnormal tau was found in the transentorhinal region, and in 3/42
      cases this site was Gallyas-positive for isolated NFTs (NFT stage I). Of 26 cases
      that lacked abnormal tau in the transentorhinal region, 4 did not show pretangle
      material at subcortical sites. The remaining 22 of these same 26 cases, however,
      had subcortical lesions confined to non-thalamic nuclei with diffuse projections
      to the cerebral cortex, and, remarkably, in 19/22 individuals the pretangle
      material was confined to the noradrenergic coeruleus/subcoeruleus complex.
      Assuming the pretangle alterations are not transient and do not regress, these
      findings may indicate that the Alzheimer's disease-related pathological process
      leading to neurofibrillary tangle formation does not begin in the cerebral cortex
      but, rather, in select subcortical nuclei, and it may start quite early, i.e.,
      before puberty or in early young adulthood.

PMID- 21170539
TI  - Systemic therapy of plaque-type psoriasis ameliorates endothelial cell function:
      results of a prospective longitudinal pilot trial.
AB  - Severe psoriasis is associated with significant cardiovascular mortality. We
      therefore investigated the effects of systemic therapy on the cardiovascular risk
      of psoriasis patients. Thirteen consecutive patients receiving fumaric acid
      esters were included and followed for 24 weeks both clinically and by means of
      laboratory monitoring, 10 completed the study. Eight of ten patients showed a
      PASI-50 response. Two of three patients with clinical insulin resistance
      (Homeostasis Model Assessment of insulin resistance >2.5) showed normal insulin
      responsiveness at the end of the study. Clinical improvement was paralleled by a
      reduction of high-sensitive CRP serum levels (median -25%). There was a trend
      toward reduced serum levels for the vascular endothelial growth factor (median 
      10%) and resistin (median -4%), while the potentially cardio-protective
      adiponectin showed a trend toward increased serum levels under therapy (median
      +19%). Systemic endothelial function assessed by venous occlusion plethysmography
      revealed an improvement of endothelial vasodilator function after 24 weeks of
      treatment (p < 0.02). This is the first prospective study documenting an
      amelioration of endothelial cell function in patients with moderate-to-severe
      plaque-type psoriasis under effective continuous systemic therapy. Future studies
      need to compare the cardioprotective effects of different treatment modalities,
      based on hard end points such as the rate of myocardial infarction.

PMID- 21170540
TI  - Cannabinoid hyperemesis syndrome: an underreported entity causing nausea and
      vomiting of pregnancy.
AB  - INTRODUCTION: In the western world, cannabis is the most widely used drug of
      abuse. Cannabinoid hyperemesis syndrome, which seems to be a rare paradoxical
      reaction in individuals with a particular predisposition, is characterized by
      cyclic severe nausea and vomiting in long-term cannabis users. While the symptoms
      are unresponsive to antiemetic drugs, compulsive hot baths result in a
      considerable symptom relief. METHODS: We report the first case of cannabinoid
      hyperemesis syndrome in pregnancy. A 26-year-old patient was admitted to our
      clinic in the 10th week of gestation. CONCLUSION: Before undertaking time
      consuming and expensive medical examinations to rule out other medical reasons
      for therapy-resistant hyperemesis in pregnancy, obstetricians should determine
      whether compulsive bathing or showering provides symptomatic relief and ask
      specific questions regarding possible/suspected cannabis consumption.

PMID- 21170541
TI  - Gestational diabetes: a strong independent risk factor for severe neonatal
      respiratory failure after 34 weeks.
AB  - PURPOSE: To evaluate if gestational diabetes (GD) exposes neonates delivered
      after 34 weeks to an increased risk of severe neonatal respiratory failure (NRF).
      METHODS: Data from 3,237 women who delivered after 34 weeks with systematic
      screening for GD were analyzed. Diagnosis of severe NRF required the association
      of clinical and radiological criteria with a minimum of 24 h of ventilation and
      admission to neonatal intensive care unit. RESULTS: A total of 166 (5.1%) cases
      of GD were identified. Severe NRF was diagnosed in 7 (4.21%) cases among women
      with GD as compared to 13 (0.42%) in others (p < 0.001). The rate of severe NRF
      was also significantly higher in cases of premature delivery (p < 0.001), fetal
      growth retardation (p < 0.001), and cesarean section (p = 0.005). After
      adjustment for these variables, GD was identified as an independent risk factor
      for NRF (AOR 11.55, 95% CI 3.9-33.9, p < 0.001). Two other risk factors were also
      identified: late preterm delivery (AOR 6.13, 95% CI 1.8-21.2, p = 0.004); and
      hypotrophy (AOR 9.16, 95% CI 2.7-30.5, p < 0.001). CONCLUSIONS: GD is an
      independent risk factor for severe NRF after 34 weeks. Neonates from such
      pregnancies should be monitored carefully.

PMID- 21170542
TI  - Primary umbilical endometriosis: a rare entity.
AB  - Primary umbilical endometriosis accounts for 0.5-1% of extragenital
      endometriosis. Clinical presentation is typical and treatment involves complete
      excision. It is important to consider it in differential diagnosis of an
      umbilical nodule.

PMID- 21170543
TI  - Fertility outcome after conservative surgery for borderline ovarian tumors: a
      single center experience.
AB  - OBJECTIVE: The present study aims to document the experience of a single center
      on the reproductive outcome of a cohort of women who were treated with
      conservative surgery for borderline ovarian tumors and to specify whether their
      fertility potential is associated with age, tumor histology and surgery type.
      METHODS: A total of 55 women who had undergone conservative surgery for
      borderline ovarian tumors between January 1999 and January 2009 were eligible.
      Recurrence rate, fertility outcome and the number of pregnancies were analyzed
      retrospectively. RESULTS: Among the study group, 11 women were not sexually
      active both at the time of surgery and during the follow-up period. Thus, a total
      of 44 patients attempted pregnancy after conservative surgery and 52.3% of them
      (23 out of 44) were able to conceive either spontaneously or by in vitro
      fertilization. The ability to conceive was shown to be associated with age, tumor
      histology and type of conservative surgery. As expected, the fertility potential
      correlated positively with decreasing age (correlation coefficient = 0.705, p =
      0.001). Moreover, the existence of non-serous histology and the implementation of
      unilateral cystectomy were found to be associated with the ability to reach a
      clinical pregnancy (correlation coefficient = 0.585, p = 0.001 and correlation
      coefficient = 0.587, p = 0.001, respectively). CONCLUSIONS: The primary treatment
      of borderline ovarian tumors refers to conservative surgery. Younger age, non
      serous histology and unilateral cystectomy appear to be associated with favorable
      reproductive outcome in women who undergo conservative surgery for borderline
      malignancy of ovary.

PMID- 21170544
TI  - Human papillomavirus infection in pregnant women.
AB  - INTRODUCTION: Human papillomavirus (HPV) is the most common sexually transmitted
      infection in the world. It has been established that about 70% of the sexually
      active population are exposed to this infection. The HPV prevalence rate among
      pregnant women ranges from 5.5 to 65.0%. Studies on HPV infection in pregnant
      women have yielded inconsistent results, including HPV prevalence, and HPV
      clearance. AIM: Our aim is to determine the prevalence of HPV infection in
      pregnant women, to identify the types of the virus, and to evaluate the changes
      of prevalence of HPV infection depending on the trimester of pregnancy in
      Lithuania. METHODS: Two hundred and thirteen pregnant women who were attending
      centres of the central outpatient clinic of Vilnius city (Lithuania) in 2008-2010
      were studied. These women were examined for HPV infection and its type by
      polymerase chain reaction. Tests were performed on the first and third
      trimesters. The statistical analysis was done using SPSS17 and Excel software.
      RESULTS: At the beginning of the pregnancy (first trimester of pregnancy), HPV
      infection was detected in 17.8% of the pregnant women (38 from 213); high
      oncogenic risk HPV types were identified for 52.6% of the HPV-positive pregnant
      women. At the end of the pregnancy (third trimester of pregnancy), HPV was
      identified in 10.3% of the pregnant women (15 out of 146); high-risk HPV types
      were identified for 66.7%. CONCLUSION: Our study shows the high prevalence of HPV
      infection in pregnant women in Lithuania. The majority of pregnant women's HPV
      infection was cleared during the pregnancy. Only in a few cases a new HPV
      infection was detected.

PMID- 21170545
TI  - Genetic identification of highly putrefied bodies using DNA from soft tissues.
AB  - The identification of putrefied bodies is a common task in forensic routine work.
      The deceased are usually identified by dental records, fingerprinting, or--in
      cases where no such data are available--DNA analysis. However, with progressive
      putrefaction, DNA integrity is rapidly decreasing. Genetic analysis may then be
      greatly impaired, if not impossible. The aim of our study was to establish an
      efficient procedure to successfully extract and amplify DNA from soft tissues of
      bodies in different stages of putrefaction. Soft tissues-unlike teeth or bones
      usually allow the application of fast and easy-to-use extraction protocols. DNA
      was extracted from different tissues (aorta, kidney, liver, and skeletal muscle)
      taken at autopsy using a commercially available DNA extraction kit, and DNA
      quality and quantity were controlled by agarose gel electrophoresis and real-time
      polymerase chain reaction (PCR). Presence of mitochondrial DNA was tested using a
      highly sensitive duplex PCR. Short tandem repeat analysis was done using the
      AmpFlSTR Identifiler kit. Additionally, mitochondrial DNA sequencing was
      performed. After DNA extraction from at least two different tissues-preferably
      the kidney and the aorta-with the extraction kit based on the Nucleobond method,
      a successful amplification of at least eight loci was possible in 17 out of 18
      cases, and 12 or more loci could be amplified in 15 cases.

PMID- 21170546
TI  - Candida albicans and Pseudomonas aeruginosa adhesion on soft contact lenses.
AB  - BACKGROUND: In this study it was aimed to determine the adherence of Pseudomonas
      and Candida to contact lens surfaces, and to determine the difference in
      adherence between five contact lens types. Biofilm-negative control strains were
      also used to emphasize the difference between biofilm-positive and biofilm
      negative strains in adherence. METHODS: Five different soft contact lenses were
      used to investigate the adherence of Pseudomonas aeruginosa and Candida albicans
      strains. P. aeruginosa ATCC 27853, P. aeruginosa ATCC 10145, C.albicans ATCC
      10231 standard strains and C. albicans clinical isolate were included in the
      study. Slime formation was investigated by two methods; modified Christensen
      macrotube method, and a modified microtiter plate test. P. aeruginosa and C.
      albicans slime formation on soft contact lenses was studied in adherence and
      separation phases. Pseudomonas and Candida suspensions were serially diluted and
      inoculated to blood agar and sabouraud dextrose agar surfaces respectively. After
      overnight incubation, the colonies were counted. Sterile unworn contact lenses
      were used as negative controls, and bacterial and fungal culture suspensions were
      used as positive controls. The experiments were conducted in three parallel
      series. RESULTS: The number of adherent Pseudomonas was as follows from high to
      low in polymacon, etafilcon A, hilafilcon, ocufilcon and lotrafilcon contact
      lenses respectively. However, the number of adherent yeast were determined higher
      in lotrafilcon and ocufilcon contact lenses, followed by hilafilcon, etafilcon A
      and polymacon contact lenses. Biofilm-negative Pseudomonas ATCC standard strain
      and Candida clinical isolate were used to confirm that the number of adherent
      cells were lower than the biofilm-positive ones. CONCLUSIONS: This study
      demonstrates that in addition to the contact lens properties, the microorganisms
      themselves and their interactions with the lens material also play an important
      role in adherence.

PMID- 21170547
TI  - Individual recurrence intervals after anti-VEGF therapy for age-related macular
      degeneration.
AB  - BACKGROUND: To assess the time interval to recurrent choroidal neovascular
      membrane (CNV) activity in eyes with neovascular age-related macular degeneration
      (AMD) after intravitreal anti-VEGF therapy. METHODS: Data from all patients who
      received intravitreal ranibizumab injections for neovascular AMD at the
      University of Cologne prior to February 2009 were retrospectively reviewed.
      Patients were treated on a pro re nata (PRN) basis and eyes with active CNV
      received three consecutive monthly injections. Recurrence of CNV activity was
      defined as recurrence of intra- or subretinal fluid on optical coherence
      tomography (OCT) or leakage on fluorescein angiography (FA) after initial
      resolution of fluid and leakage following anti-VEGF therapy. All eyes showing at
      least two documented recurrences of CNV activity during follow-up were included
      in this analysis. Recurrence intervals were calculated and were deemed to be
      regular or periodical if the difference between recurrence interval times was
      less than 50 days. RESULTS: Twenty-nine eyes of 28 patients met the inclusion
      criteria. Two to six recurrences were detected per case (mean 2.8 +/- 1.1
      recurrences). Recurrence intervals ranged from 41 days to 523 days (mean 5.5 +/-
      3.4 months, median 4.5 months). Twenty-two eyes (76%) showed at least two
      periodical recurrence intervals. In 12 eyes (41%), all recurrences occurred at
      regular intervals (2-4 recurrences, mean 2.3 +/- 0.6 recurrences). Seven eyes
      (24%) showed irregular recurrence intervals (2-3 recurrences, mean 2.1 +/- 0.4
      recurrences). All 11 eyes with a classic CNV lesion component showed at least two
      periodical recurrence intervals. Eyes with occult CNV lesions showed periodical
      recurrence intervals in 11 out of 18 cases (61%). CONCLUSIONS: Preliminary data
      indicate that periodical recurrences of CNV activity may be seen in eyes with
      neovascular AMD undergoing anti-VEGF therapy. Knowledge of individual recurrence
      interval times may allow for the development of an individualized treatment plan
      and prophylactic therapy.

PMID- 21170548
TI  - AXY3 encodes a alpha-xylosidase that impacts the structure and accessibility of
      the hemicellulose xyloglucan in Arabidopsis plant cell walls.
AB  - Xyloglucan is the most abundant hemicellulose in the walls of dicots such as
      Arabidopsis. It is part of the load-bearing structure of a plant cell and its
      metabolism is thought to play a major role in cell elongation. However, the
      molecular mechanism by which xyloglucan carries out this and other functions in
      planta is not well understood. We performed a forward genetic screen utilizing
      xyloglucan oligosaccharide mass profiling on chemically mutagenized Arabidopsis
      seedlings to identify mutants with altered xyloglucan structures termed axy
      mutants. One of the identified mutants, axy3.1, contains xyloglucan with a higher
      proportion of non-fucosylated xyloglucan subunits. Mapping revealed that axy3.1
      contains a point mutation in XYLOSIDASE1 (XYL1) known to encode for an apoplastic
      glycoside hydrolase releasing xylosyl residues from xyloglucan oligosaccharides
      at the non-reducing end. The data support the hypothesis that AXY3/XYL1 is an
      essential component of the apoplastic xyloglucan degradation machinery and as a
      result of the lack of function in the various axy3-alleles leads not only to an
      altered xyloglucan structure but also a xyloglucan that is less tightly
      associated with other wall components. However, the plant can cope with the
      excess xyloglucan relatively well as the mutant does not display any visible
      growth or morphological phenotypes with the notable exception of shorter siliques
      and reduced fitness. Taken together, these results demonstrate that plant
      apoplastic hydrolases have a larger impact on wall polymer structure and function
      than previously thought.

PMID- 21170549
TI  - Educational paper: Primary immunodeficiencies in children: a diagnostic
      challenge.
AB  - Primary immunodeficiencies (PIDs) are characterized by an increased
      susceptibility to infections due to defects in one ore more components of the
      immune system. Although most PIDs are relatively rare, they are more frequent
      than generally acknowledged. Early diagnosis and treatment of PIDs save lives,
      prevent morbidity, and improve quality of life. This early diagnosis is the task
      of the pediatrician who encounters the child for the first time: he/she should
      suspect potential PID in time and perform the appropriate diagnostic tests. In
      this educational paper, the first in a series of five, we will describe the most
      common clinical presentations of PIDs and offer guidelines for the diagnostic
      process, as well as a brief overview of therapeutic possibilities and prognosis.

PMID- 21170550
TI  - A literature-based meta-analysis taxane-based doublet versus single-agent taxane
      chemotherapy in patients with advanced breast cancer.
AB  - PURPOSE: Clinical trials have reported conflicting results as to whether taxane
      based doublet improves outcome over single-agent taxane in patients with advanced
      breast cancer. METHODS: We performed a meta-analysis comparing primary and
      secondary end points of taxane-based doublet with single-agent taxane
      chemotherapy in patients with advanced breast cancer and prior anthracycline
      treatment. The event-based relative risk ratio (RR) with 95% confidence intervals
      (95% CI) was derived, and a test of heterogeneity was applied. RESULTS: Four
      eligible trials (2,343 patients) were selected from 488 studies that initially
      were identified. A significant difference in favoring taxane-based doublet over
      single-agent taxane was observed in progression-free survival (PFS) (RR, 1.33;
      95% CI, 1.02-1.75; P = 0.039) and partial response (PR) (RR, 1.43; 95% CI, 1.10
      1.86; P = 0.008). The ORR was higher for patients receiving taxane-based doublet,
      although not statistically significant (RR, 1.17; 95% CI, 0.91-1.50; P = 0.220).
      Whereas there was no difference in 1-year survival rate (1-year SR) (RR, 1.05;
      95% CI, 0.94-1.17; P = 0.422), clinical benefit (CB) (RR, 1.02; 95% CI, 0.95
      1.09; P = 0.642), and complete response (CR) (RR, 0.75; 95% CI, 0.31-1.79; P =
      0.512). Toxicities did not differ significantly except stomatitis and diarrhea.
      CONCLUSION: Taxane-based doublet appeared to improve PFS and PR compared with
      single-agent taxane in the treatment of patients with advanced breast cancer.
      Further prospective, randomized, controlled trials will be necessary.

PMID- 21170551
TI  - The effect of exemestane and tamoxifen on bone health within the Tamoxifen
      Exemestane Adjuvant Multinational (TEAM) trial: a meta-analysis of the US,
      German, Netherlands, and Belgium sub-studies.
AB  - PURPOSE: We performed a meta-analysis of three sub-studies of the randomized
      Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial to determine the effects
      of exemestane and tamoxifen on bone health. METHODS: Patients received exemestane
      or tamoxifen as adjuvant therapy for hormone receptor-positive breast cancer.
      Bone mineral density (BMD) was assessed at baseline and after 12 and 24 months of
      treatment. Bone turnover markers were also measured. RESULTS: Patients receiving
      tamoxifen showed a mean increase from baseline in lumbar spine BMD of 1.2% at
      month 12 and 0.2% at month 24. Patients receiving exemestane showed a mean
      decrease from baseline of 2.6% after 12 months and 3.5% after 24 months. There
      were significant differences in the changes in lumbar spine BMD between treatment
      groups (P < 0.0001 at both time points). Changes in BMD from baseline at the
      total hip were also significantly different between exemestane and tamoxifen (P <
      0.05 at both time points). Bone turnover markers decreased from baseline with
      tamoxifen and increased with exemestane. CONCLUSIONS: Exemestane resulted in
      decreases in BMD and increases in bone turnover markers. BMD increased and bone
      turnover markers decreased with tamoxifen.

PMID- 21170552
TI  - Revisiting the anatomy of the central nervous system of a hemimetabolous model
      insect species: the pea aphid Acyrthosiphon pisum.
AB  - Aphids show a marked phenotypic plasticity, producing asexual or sexual and
      winged or wingless morphs depending on environmental conditions and season. We
      describe here the general structure of the brain of various morphs of the pea
      aphid Acyrthosiphon pisum. This is the first detailed anatomical study of the
      central nervous system of an aphid by immunocytochemistry (synapsin, serotonin,
      and several neuropeptides), ethyl-gallate staining, confocal laser scanning
      microscopy, and three-dimensional reconstructions. The study has revealed well
      developed optic lobes composed of lamina, medulla, and lobula complex. Ocelli are
      only present in males and winged parthenogenetic females. The central complex is
      well-defined, with a central body divided into two parts, a protocerebral bridge,
      and affiliated lateral accessory lobes. The mushroom bodies are ill-defined,
      lacking calyces, and only being visualized by using an antiserum against the
      neuropeptide orcokinin. The antennal lobes contain poorly delineated glomeruli
      but can be clearly visualized by performing antennal backfills. On the basis of
      our detailed description of the brain of winged and wingless parthenogenetic A.
      pisum females, an anatomical map is now available that should improve our
      knowledge of the way that these structures are involved in the regulation of
      phenotypic plasticity.

PMID- 21170553
TI  - Fabrication of porous polycaprolactone/hydroxyapatite (PCL/HA) blend scaffolds
      using a 3D plotting system for bone tissue engineering.
AB  - For tissue engineering and regeneration, a porous scaffold with interconnected
      networks is needed to guide cell attachment and growth/ingrowth in three
      dimensional (3D) structure. Using a rapid prototyping (RP) technique, we designed
      and fabricated 3D plotting system and three types of scaffolds: those from
      polycaprolactone (PCL), those from PCL and hydroxyapatite (HA), and those from
      PCL/HA and with a shifted pattern structure (PCL/HA/SP scaffold). Shifted pattern
      structure was fabricated to increase the cell attachment/adhesion. The PCL/HA/SP
      scaffold had a lower compressive modulus than PCL and PCL/HA scaffold. However,
      it has a better cell attachment than the scaffolds without a shifted pattern. MTT
      assay and alkaline phosphatase activity results for the PCL/HA/SP scaffolds were
      significantly enhanced compared to the results for the PCL and PCL/HA scaffolds.
      According to their degree of cell proliferation/differentiation, the scaffolds
      were in the following order: PCL/HA/SP > PCL/HA > PCL. These 3D scaffolds will be
      applicable for tissue engineering based on unique plotting system.

PMID- 21170554
TI  - Experience with palliative care in patients with advanced cancer at a tertiary
      care hospital in a developing country.
AB  - The importance of palliative care in patients with advanced cancer is
      established. Reports on the experience with palliative care in the Middle East
      region are limited. A prospective study was performed to characterize the
      palliative care experience at a tertiary care center in Lebanon and to identify
      the profile of patients requiring palliative care. This communication highlights
      the results of the study. Authors conclude that the profile of needs for
      individuals requiring palliative care in Lebanon is similar to westernized
      countries. Revisiting the continuum of cancer care is called for to better
      identify the optimal timing of intervention and avoid end of life distress.

PMID- 21170555
TI  - Endoscopic placement of a new short-term biodegradable pancreatic and biliary
      stent in an animal model: a preliminary feasibility study (with videos).
AB  - BACKGROUND AND PURPOSE: Recently, biodegradable pancreatic stents have been
      designed and placed in vivo and in vitro. The aim of this study is to investigate
      the feasibility of endoscopic stenting using the novel, braided, self-expandable,
      biodegradable, pancreatic and biliary stent in a pig model. METHODS: A braided,
      self-expandable, biodegradable stent was endoscopically placed into the
      pancreatic duct and bile duct in 4 pigs. Eventually, necropsy was performed to
      evaluate the stent placement after the procedure. RESULTS: Pancreatic and biliary
      stents were successfully inserted and easily deployed across the papilla into the
      main pancreatic duct and bile duct, respectively, in all the animals under
      endoscopic and fluoroscopic guidance. Necropsy performed immediate following
      stent placement, found that stents had been placed across the papilla and stent
      expansion had occurred in all cases. CONCLUSIONS: Although this stent is not
      radiopaque and the number of cases was small in this experimental study,
      endoscopic stenting using this novel, braided, self-expandable, biodegradable,
      pancreatic and biliary stent was feasible in the pig model. Further animal
      studies to evaluate the short-term patency, tissue reactivity and degradability
      of the stents are warranted.

PMID- 21170556
TI  - Reduction in external ventricular drain infection rate. Impact of a minimal
      handling protocol and antibiotic-impregnated catheters.
AB  - INTRODUCTION: Many strategies have been developed with the aim of reducing
      external ventricular drain-related infections. Antibiotic-impregnated catheters
      are one of them. MATERIAL AND METHODS: We report 648 cases of external
      ventricular drain from a total of 534 patients treated at the Virgen del Rocio
      Hospital between 1995 and 2006. Three subgroups were considered: group 1 included
      patients treated between 1995 and 2000, as well as a total of 190 external
      ventricular drains and 59 cases of infection (31.05%); group 2, with patients
      treated between 2000 and 2004 and managed with a minimal handling protocol,
      included 210 external ventricular drains and nine cases of infection (4.29%); and
      group 3, treated between 2004 and 2006, with 248 external ventricular drains and
      six cases of infection (2.41%). This latter subgroup included patients managed
      with a minimal handling protocol and antibiotic-impregnated catheters. RESULTS:
      Infection rate was 17% when non-antibiotic-impregnated catheters were employed
      and 2.41% when antibiotic-impregnated catheters were inserted (p < 0.001). This
      difference was statistically significant before and after the introduction of a
      minimal handling protocol, with percentages of 5.31% and 3.27%, respectively (p <
      0.001; odds ratio 0.08; absolute risk reduction 27.26%). However, no
      statistically significant difference was observed in infection rate when the
      impact of a minimal handling protocol was considered: 4.29% when only the
      protocol was introduced and 2.41% when both the protocol and antibiotic
      impregnated catheters were used (p > 0.05). CONCLUSION: Minimal handling
      protocols constitute an essential strategy in the reduction of external
      ventricular drain-related infections. Besides that, the use of antibiotic
      impregnated catheters may reduce infection-related hospital costs.

PMID- 21170557
TI  - Randomized controlled trial of 2.5-cm versus 3.5-cm mesial temporal resection-
      Part 2: volumetric resection extent and subgroup analyses.
AB  - BACKGROUND: This paper is addressing outcome differences in interesting subgroups
      from a previous randomized controlled trial of the extent of mesial temporal lobe
      resection (TLR) for drug-resistant epilepsy, by looking at effects of
      randomization, intended resection group, center, and true resection extent on
      seizure outcome. METHODS: One hundred and seventy-nine cases with volumetrically
      assessed resection extent were used. Analyses of the extent of resection and
      subgroups and within subgroups for the two treatment arms will be performed,
      looking for confounding factors and using statistical methods (chi-square test,
      logistic regression analysis, and two-factorial ANOVA). RESULTS: True resection
      extent varied considerably. Outcome comparison for right versus left resections,
      subgroups with mesial temporal sclerosis (MTS), or largest and smallest
      resections revealed no remarkable difference, compared to overall class I
      outcome. The intent-to-treat analyses within these subgroups revealed differences
      for class I outcome, albeit lacking in significance, except for better TLR
      outcome. Small true resection volume differences or randomization into the two
      resection groups could not explain the outcome differences between the selective
      amygdalohippocampectomy (SAH) and TLR subgroups. Logistic regression analysis
      showed an interaction between intended resection length and surgery type,
      confirming the impression of different impacts of the intended resection length
      under the two surgery types. The outcome difference between SAH and TLR was more
      likely explained by a center effect. In a two-factorial ANOVA for resected
      hippocampal volume, Engel outcome class I, and resection type, the outcome was
      not found to be correlated with true resection volume. A multifactorial logistic
      regression showed a mild interaction between the resection type with center on
      the Engel outcome class, extent of resection, and surgery type interacted, as did
      the extent of resection and center. CONCLUSION: Patients with quite similar
      extent of resection can be seizure free or non-seizure free. In this cohort,
      seizure freedom rates fell again when the extent of mesial resection was
      maximized. Differences in class I outcome for SAH and TLR were not due to
      erroneous randomization, true resection extent, or presence of MTS, but were
      influenced by a center effect. Subgroup analyses did not help to provide
      arguments to favor one surgery type over the other.

PMID- 21170558
TI  - Randomized controlled trial of 2.5-cm versus 3.5-cm mesial temporal resection in
      temporal lobe epilepsy--Part 1: intent-to-treat analysis.
AB  - BACKGROUND: Only one prospective randomized study on the extent of mesial
      resection in surgery for temporal lobe epilepsy (TLE) exists. This randomized
      controlled trial (RCT) examines whether 3.5-cm mesial resection is leading to a
      better seizure outcome than a 2.5-cm resection. METHODS: Three epilepsy surgery
      centers using similar MRI protocols, neuropsychological tests, and resection
      types for TLE surgery included 207 patients in a RCT with pre- and postoperative
      volumetrics. One hundred and four patients were randomized into a 2.5-cm
      resection group and 103 patients into a 3.5-cm resection group, i.e., an intended
      minimum resection length of 25 versus 35 mm for the hippocampus and
      parahippocampus. Primary outcome measure was seizure freedom Engel class I
      throughout the first year. The study was powered to detect a 20% difference in
      class I outcome. Seizure outcome was available for 207 patients, complete
      volumetric results for 179 patients. Outcome analysis was restricted to control
      of successful randomization and an intent-to-treat analysis of seizure outcome.
      RESULTS: The mean true resection volumes were significantly different for the 2.5
      cm and 3.5-cm resection groups; thus, the randomization was successful. Median
      resection volume in the 2.5-cm group was 72.86% of initial volume and 83.44% in
      the 3.5-cm group. At 1 year, seizure outcome Engel class I was 74% in the 2.5-cm
      and 72.8% in the 3.5-cm resection group. CONCLUSIONS: The primary intent-to-treat
      analysis did not show a different seizure freedom rate for the more posteriorly
      reaching 3.5-cm resection group. It appears possible that not maximal volume
      resection but adequate volume resection leads to good seizure freedom.

PMID- 21170559
TI  - 6-Mercaptopurine reverses experimental vasospasm and alleviates the production of
      endothelins in NO-independent mechanism-a laboratory study.
AB  - INTRODUCTION: Increased endothelin-1 (ET-1) production and diminished nitric
      oxide synthase (NOS) bioavailability has been observed in aneurysmal subarachnoid
      hemorrhage (SAH). The authors previously found that 6-mercaptopurine (6-mp) is
      effective in preventing and reversing arterial narrowing in a rodent SAH model.
      This present study is of interest to examine the effect of 6-mp on ET
      1/endothelial nitric oxide synthase (eNOS) in this animal model. METHODS: A
      rodent double hemorrhage SAH model was employed. Animals were randomly assigned
      to six groups (sham, SAH only, vehicle, 0.5, 1.0 and 2 mg kg(-1) day(-1) 6-mp
      treatment). Monoclonal CD45 immunostaining was utilized to evaluate monocytes and
      microglia. The level of pro-inflammatory cytokines, such as IL-1, IL-6 and TNF
      alpha(RT-PCR), and ET-1 (ELISA) was measured. The basilar arteries (BAs) were
      harvested and sliced, and their cross-sectional areas were determined.
      Radiolabeled NOS assay kit was applied to detect eNOS. RESULTS: Morphologically,
      convolution of internal elastic lamina, endothelial cells distortion, and
      necrotic smooth muscle were prevalently present in the basilar artery of SAH
      groups, which was absent in the 1 and 2 mg kg(-1) day(-1) 6-mp plus SAH group or
      the healthy controls. Significant vasospasm was noted in the vehicle group (lumen
      patency, 54.6%, p <= 0.01 compared with the sham group), but it was less
      prominent in the 2 mg kg(-1) day(-1) 6-mp treatment group (lumen patency, 87.6%,
      p < 0.05). In addition, administration with 2 mg kg(-1) day(-1) 6-mp reduced
      cytokine levels by 11%, 47%, and 34% for IL-1, IL-6, and TNF-alpha, respectively,
      and increased ET-1 levels were found in all the animals subject to SAH (SAH only,
      SAH plus vehicle, SAH plus 0.5 and 1.0 mg kg(-1) day(-1) 6-mp) except in the 2 mg
      kg(-1) day(-1) 6-mp SAH group, when compared with the healthy controls (no SAH).
      Meanwhile, treatment with 6-mp did not induce the levels of expressed eNOS in BAs
      in the 6-mp groups (0.5, 1.0, and 2 mg kg(-1) day(-1) 6-mp plus SAH) when
      compared with that in the SAH groups (p > 0.1). CONCLUSION: In summary, treatment
      with 6-mp decreased the release of pro-inflammatory cytokines and diminished
      experimental vasospasm. This study offered first evidence that 6-mp dose
      dependently reduces the level of ET-1 in a NO-independent mechanism, which
      corresponds to its antivasospastic effect in the condition of chronic vasospasm.

PMID- 21170560
TI  - Lysine transporters in human trypanosomatid pathogens.
AB  - In previous studies we characterized arginine transporter genes from Trypanosoma
      cruzi and Leishmania donovani, the etiological agents of chagas disease and kala
      azar, respectively, both fatal diseases in humans. Unlike arginine transporters
      in higher eukaryotes that transport also lysine, these parasite transporters
      translocate only arginine. This phenomenon prompted us to identify and
      characterize parasite lysine transporters. Here we demonstrate that LdAAP7 and
      TcAAP7 encode lysine-specific permeases in L. donovani and T. cruzi,
      respectively. These two lysine permeases are both members of the large amino
      acid/auxin permease family and share certain biochemical properties, such as
      specificity and Km. However, we evidence that LdAAP7 and TcAAP7 differ in their
      regulation and localization, such differences are likely a reflection of the
      dissimilar L. donovani and T. cruzi life cycles. Failed attempts to delete both
      alleles of LdAAP7 support the premise that this is an essential gene that encodes
      the only lysine permeases expressed in L. donovani promastigotes and T. cruzi
      epimastigotes, respectively.

PMID- 21170561
TI  - New chelating ligands for Co(III)-based peptide-cleaving catalysts selective for
      pathogenic proteins of amyloidoses.
AB  - The Co(III) complex of 1,4,7,10-tetraazacyclododecane has been employed as the
      catalytic center of target-selective peptide-cleaving catalysts in previous
      studies. As new chelating ligands for the Co(III) ion in the peptide-cleaving
      catalysts, 1-oxo-4,7,10-triazacyclodedecane, 1-aryl-1,4,7,10-tetraazacyclodecane,
      and 7-aryl-1-oxo-4,7,10-triazacyclodecane were examined in the present study. A
      chemical library comprising 612 derivatives of the Co(III) complex of the new
      chelating ligands was constructed. The catalyst candidates were tested for their
      activity to cleave the soluble oligomers of amyloidogenic peptides amyloid beta
      42 and human islet amyloid polypeptide (h-IAPP), which are believed to be the
      pathogenic species for Alzheimer's disease and type 2 diabetes mellitus,
      respectively. One derivative of the Co(III) complex of 1-aryl-1,4,7,10
      tetraazacyclodecane was found to cleave the oligomers of h-IAPP. Cleavage
      products were identified and cleavage yields were measured at various catalyst
      concentrations for the action of the new catalyst. The present results reveal
      that effective catalytic drugs for amyloidoses may be obtained by using Co(III)
      complexes of various chelating ligands.

PMID- 21170562
TI  - Desulforubrerythrin from Campylobacter jejuni, a novel multidomain protein.
AB  - A novel multidomain metalloprotein from Campylobacter jejuni was overexpressed in
      Escherichia coli, purified, and extensively characterized. This protein is
      isolated as a homotetramer of 24-kDa monomers. According to the amino acid
      sequence, each monomer was predicted to contain three structural domains: an N
      terminal desulforedoxin-like domain, followed by a four-helix bundle domain
      harboring a non-sulfur MU-oxo diiron center, and a rubredoxin-like domain at the
      C-terminus. The three predicted iron sites were shown to be present and were
      studied by a combination of UV-vis, EPR, and resonance Raman spectroscopies,
      which allowed the determination of the electronic and redox properties of each
      site. The protein contains two FeCys(4) centers with reduction potentials of +240
      mV (desulforedoxin-like center) and +185 mV (rubredoxin-like center). These
      centers are in the high-spin configuration in the as-isolated ferric form. The
      protein further accommodates a MU-oxo-bridged diiron site with reduction
      potentials of +270 and +235 mV for the two sequential redox transitions. The
      protein is rapidly reoxidized by hydrogen peroxide and has a significant NADH
      linked hydrogen peroxide reductase activity of 1.8 MUmol H(2)O(2) min(-1) mg(-1).
      Owing to its building blocks and its homology to the rubrerythrin family, the
      protein is named desulforubrerythrin. It represents a novel example of the large
      diversity of the organization of domains exhibited by this enzyme family.

PMID- 21170563
TI  - Nitrite reduction by xanthine oxidase family enzymes: a new class of nitrite
      reductases.
AB  - Mammalian xanthine oxidase (XO) and Desulfovibrio gigas aldehyde oxidoreductase
      (AOR) are members of the XO family of mononuclear molybdoenzymes that catalyse
      the oxidative hydroxylation of a wide range of aldehydes and heterocyclic
      compounds. Much less known is the XO ability to catalyse the nitrite reduction to
      nitric oxide radical (NO). To assess the competence of other XO family enzymes to
      catalyse the nitrite reduction and to shed some light onto the molecular
      mechanism of this reaction, we characterised the anaerobic XO- and AOR-catalysed
      nitrite reduction. The identification of NO as the reaction product was done with
      a NO-selective electrode and by electron paramagnetic resonance (EPR)
      spectroscopy. The steady-state kinetic characterisation corroborated the XO
      catalysed nitrite reduction and demonstrated, for the first time, that the
      prokaryotic AOR does catalyse the nitrite reduction to NO, in the presence of any
      electron donor to the enzyme, substrate (aldehyde) or not (dithionite). Nitrite
      binding and reduction was shown by EPR spectroscopy to occur on a reduced
      molybdenum centre. A molecular mechanism of AOR- and XO-catalysed nitrite
      reduction is discussed, in which the higher oxidation states of molybdenum seem
      to be involved in oxygen-atom insertion, whereas the lower oxidation states would
      favour oxygen-atom abstraction. Our results define a new catalytic performance
      for AOR-the nitrite reduction-and propose a new class of molybdenum-containing
      nitrite reductases.

PMID- 21170564
TI  - Value and utility of disease-specific and generic instruments for assessing
      disability in patients with migraine, and their relationships with health-related
      quality of life.
AB  - The aim of this paper is to explore the relationships between health-related
      quality of life (HRQoL), assessed with the Short Form-36 (SF-36), and disability
      in adult migraineurs using both disease-specific and generic tools, the WHO
      Disability Assessment Schedule II (WHO-DAS II) and with the Migraine Disability
      Assessment questionnaire (MIDAS). Significant differences were observed between
      patients with minimal/mild and moderate/severe MIDAS disability grades for Role
      Physical, Bodily Pain, General Health, Vitality, Social Functioning and Physical
      Composite Score of the SF-36; in the WHO-DAS II for household activities,
      participation in society and for summary score. WHO-DAS II and MIDAS provide
      complementary information on the intensity and the frequency of problems in
      performing daily activities, and could be used jointly. Our findings indicate
      that these issues are relevant for patients' health status and should be taken
      into account in future research on migraine as important secondary outcomes of
      treatment interventions.

PMID- 21170565
TI  - Molecular detection and confirmation of Neisseria gonorrhoeae in urogenital and
      extragenital specimens using the Abbott CT/NG RealTime assay and an in-house
      assay targeting the porA pseudogene.
AB  - Culture for detection of Neisseria gonorrhoeae (NG) is being replaced by
      molecular assays, but difficulties are observed with false positive and negatives
      results, especially for extragenital samples. This study evaluates the Abbott
      CT/NG Real-Time assay and a real-time porA pseudogene assay. Samples (n = 600)
      from a mixed prevalence Irish population include 164 male urines with
      corresponding urethral swabs, 58 endocervical swabs, 173 male pharyngeal swabs,
      205 male rectal swabs, 36 NG clinical isolates and 26 commensal Neisseria species
      isolates. There was a 100% concordance between the Abbott CT/NG Real-Time and the
      porA assay. The positivity rate was 1.2%, 1.7%, 8.1% and 5.8% for FVU/urethral
      swabs, endocervical, pharyngeal and rectal swabs, respectively. These results
      were compared to culture and discrepancies were found with nine pharyngeal and
      three rectal swabs. Seven of the 12 discrepant positive samples were sequenced
      and were confirmed "true positives". The sensitivity and specificity of the
      molecular assays was 100%. The sensitivity of the culture-based testing was 100%
      for urogenital samples but 36% and 75% for pharyngeal and rectal swabs,
      respectively. The combined Abbott CT/NG and porA assays provide a valuable
      alternative to culture and also generate a significant increase in the diagnosis
      of pharyngeal and rectal NG infection.

PMID- 21170566
TI  - Steroid treatment in patients with membranous nephropathy and hepatitis B virus
      surface antigenemia: a report of two cases.
AB  - Although the clinical benefits of antiviral treatment in the management of
      membranous nephropathy (MN) in patients with chronic hepatitis B virus (HBV)
      infection have been suggested, it should be evaluated more carefully. In this
      report, we present two cases with quiescent HBV who were administered lamivudine
      for either the initial treatment of MN or to control the reactivation of HBV
      during treatment with corticosteroids. No clinical benefit of lamivudine as an
      initial treatment was observed in one patient, which obliged us to commence
      administration of prednisolone (PSL). On the other hand, lamivudine seemed to
      play a pivotal role in the remission of an acute exacerbation of hepatitis B
      during treatment with PSL and mizoribine in the other patient. These two patients
      seemed to tolerate administration of PSL with or without an immunosuppressive
      agent well, since gradual and prompt improvements of nephrotic status were
      confirmed within a few months, thus suggesting the potential benefit of steroid
      treatment. There is little consensus regarding the optimal choice of steroids and
      immunosuppressants for the treatment of MN with chronic HBV infection, due to the
      potential for stimulation of viral replication and precipitation of hepatic
      flares. Our observations, however, suggest that treatment with PSL still should
      be reserved for quiescent HBV carriers with MN. Further studies will be required
      to determine the optimal timing and appropriate duration of antiviral treatment
      in such patients requiring long-term immunosuppression.

PMID- 21170568
TI  - Anti-smoking parenting practices: recall by and effect on children's risk of
      smoking after 3 years.
AB  - OBJECTIVES: Parent engagement in anti-smoking parenting practices was examined as
      a predictor of children's recalled exposure to these practices, the presence of
      pro-smoking risk factors in children's social environments, and children's odds
      of initiating smoking. METHODS: 1,032 parents reported level of engagement in a
      program that promoted anti-smoking parenting practices for 8-year-old children.
      1,032 children were surveyed 6 months and 3 years post-intervention; they
      reported on exposure to anti-smoking parenting practices, pro-smoking risk
      factors, and initiation of smoking. RESULTS: If parents reported high engagement
      in anti-smoking socialization, children had significantly greater recall of anti
      smoking parenting practices and significantly fewer pro-smoking risk factors up
      to 3 years post-intervention. If engagement was moderate or low, children had
      progressively lower odds of recalling anti-smoking parenting practices relative
      to controls and they were progressively less likely to differ from controls in
      exposure to pro-smoking risk factors at follow-up. CONCLUSIONS: Achieving full
      program implementation remains a significant challenge to home-based, parent-led
      approaches to smoking prevention. However, if parents fully engage in anti
      smoking parenting practices, children demonstrate protective effects up to 3
      years later.

PMID- 21170567
TI  - Overview of diagnosis and management of paediatric headache. Part II: therapeutic
      management.
AB  - A thorough evaluation of headache in children and adolescents is necessary to
      make the correct diagnosis and initiate treatment. In part 1 of this article
      (Ozge et al. in J Headache Pain, 2010), we reviewed the diagnosis of headache in
      children and adolescents. In the present part, we will discuss therapeutic
      management of primary headaches. An appropriate management requires an
      individually tailored strategy giving due consideration to both non
      pharmacological and pharmacological measures. Non-pharmacological treatments
      include relaxation training, biofeedback training, cognitive-behavioural therapy,
      different psychotherapeutic approaches or combinations of these treatments. The
      data supporting the effectiveness of these therapies are less clear-cut in
      children than in adults, but that is also true for the data supporting medical
      treatment. Management of migraine and TTH should include strategies relating to
      daily living activities, family relationships, school, friends and leisure time
      activities. In the pharmacological treatment age and gender of children, headache
      diagnosis, comorbidities and side effects of medication must be considered. The
      goal of symptomatic treatment should be a quick response with return to normal
      activity and without relapse. The drug should be taken as early as possible and
      in the appropriate dosage. Supplementary measures such as rest in a quiet,
      darkened room is recommended. Pharmaco-prophylaxis is only indicated if lifestyle
      modification and non-pharmacological prophylaxis alone are not effective.
      Although many prophylactic medications have been tried in paediatric migraine,
      there are only a few medications that have been studied in controlled trials.
      Multidisciplinary treatment is an effective strategy for children and adolescents
      with improvement of multiple outcome variants including frequency and severity of
      headache and school days missed because of headache. As a growing problem both
      children and families should be informed about medication overuse and the
      children's drug-taking should be checked.

PMID- 21170569
TI  - Primary CNS lymphoma in patients younger than 60: can whole-brain radiotherapy be
      deferred?
AB  - Whole brain radiotherapy (WBRT) has been increasingly omitted as the first
      treatment of primary central nervous system lymphoma (PCNSL) because of
      neurotoxicity risks. However, neurotoxicity risks are lower in young (<60 years)
      patients; deferring WBRT may not be necessary and may compromise disease control.
      To investigate this question, we report a consecutive series of young (<60 years)
      PCNSL patients uniformly treated with a response-adjusted approach, with WBRT
      omitted in patients with chemosensitive disease. Treatment started with induction
      chemotherapy consisting of methotrexate (3 g/m(2)), CCNU, procarbazine,
      methylprednisolone and intrathecal methotrexate, cytarabine, and
      methylprednisolone. Patients achieving complete response (CR) received five
      additional chemotherapy cycles and no further treatment. Patients with less than
      CR were treated on an individual basis, typically with WBRT or high-dose
      chemotherapy (HDC) with stem cell rescue. Sixty-four patients were included
      (median age: 47; median KPS: 70). Median progression-free survival (PFS) was 12
      months; median overall survival (OS) was 63 months (median follow-up: 108
      months). Objective response after induction was 87% (CR: 54%; PR: 33%). To date,
      salvage WBRT has been given to a total of 27 patients and HDC to 29.
      Neurotoxicity developed in five patients (none in patients treated with
      chemotherapy only). Deferring WBRT in chemosensitive patients seems to compromise
      PFS but not OS. Neurotoxicity was reduced but not eliminated, as salvage WBRT was
      frequently required. HDC and WBRT were effective salvage treatments. As the
      objective of treatment in this population is a cure, withholding WBRT may not be
      the best strategy and deserves further investigation. Ongoing studies are
      investigating whether upfront treatment with HDC can replace WBRT in this
      setting.

PMID- 21170570
TI  - Evaluation of inert and organic carriers for Verticillium lecanii spore
      production in solid-state fermentation.
AB  - Growth and sporulation of Verticillium lecanii on inert and organic carriers
      (sugar-cane bagasse, corncob, rice straw, polyurethane foam and activated carbon)
      in a solid-state fermentation process was studied. Sugar-cane bagasse and
      polyurethane foam produced 10(10) spores g(-1) dry carrier whereas corncob, rice
      straw, and activated carbon yielded, respectively 8 * 10(9), 4 * 10(9), and 3 *
      10(8) spores g(-1). Chitinase activity of the conidia was in the following order:
      sugar-cane bagasse (3.3 U mg(-1)) > wheat bran (3.0 U mg(-1)) > polyurethane foam
      (2.7 U mg(-1)). There was no significant difference (2.5-2.7 U mg(-1)) in the
      proteinase activity among the conidia from the three cultures. Scanning electron
      microscopy shows that aerial mycelium freely penetrated into the internal area of
      polyurethane foam. Sugar-cane bagasse provided enough area for vegetative hyphae
      to attach. Of the carriers analyzed, polyurethane foams and sugar-cane bagasse
      were the best carriers for V. lecanii growth and spore production.

PMID- 21170571
TI  - Selenoprotein W gene expression in the gastrointestinal tract of chicken is
      affected by dietary selenium.
AB  - Selenoprotein W (SelW) and selenium (Se) plays important roles in
      gastrointestinal function and that SelW expression in the gastrointestinal system
      of mammals is sensitive to Se levels. However, little is known about the pattern
      of SelW expression in the bird gastrointestinal tract. To investigate the
      distribution of SelW and effects of dietary Se levels on the SelW mRNA expression
      in the gastrointestinal tract tissues of birds, 1-day-old male chickens were fed
      either a commercial diet or a Se-supplemented diet containing 1.0, 2.0, 3.0 or
      5.0 mg/kg sodium selenite for 90 days. The gastrointestinal tract tissues
      (tongue, esophagus, crop, proventriculus, gizzard, duodenum, small intestine,
      cecum and rectum) were collected and examined for Se content and mRNA levels of
      SelW. The mRNA expression of SelW was detected in all tissues. The greatest
      increase in SelW mRNA levels was observed in the gizzard, whereas Se content was
      highest in the duodenum and small intestine. A significant increase in SelW mRNA
      levels was observed in the gastrointestinal tract tissues of chickens fed the
      diets containing 1-3 mg/kg sodium selenite while decreased SelW mRNA levels were
      observed in the esophagus, crop, proventriculus, gizzard, duodenum and cecum in
      chickens fed the diet containing 5 mg/kg sodium selenite. These data indicate
      that SelW is widely expressed in the gastrointestinal tract tissues of birds and
      the transcription of the SelW gene is very sensitive to dietary Se.

PMID- 21170572
TI  - Diagnostic validity of fatal cerebral strokes and coronary deaths in mortality
      statistics: an autopsy study.
AB  - Mortality statistics represent important endpoints in epidemiological studies.
      The diagnostic validity of cerebral stroke and ischemic heart disease recorded as
      the underlying cause of death in Norwegian mortality statistics was assessed by
      using mortality data of participants in the Bergen Clinical Blood Pressure Study
      in Norway and autopsy records from the Gade Institute in Bergen. In the 41 years
      of the study (1965-2005) 4,387 subjects had died and 1,140 (26%) had undergone a
      post mortem examination; 548 (12%) died from cerebral stroke and 1,120 (24%) from
      ischemic heart disease according to the mortality statistics, compared to 113
      (10%) strokes and 323 (28%) coronary events registered in the autopsy records.
      The sensitivity and positive predictive value of fatal cerebral strokes in the
      mortality statistics were 0.75, 95% confidence interval (CI) [0.66, 0.83] and
      0.86 [0.77, 0.92], respectively, whereas those of coronary deaths were 0.87
      [0.84, 0.91] and 0.85 [0.81, 0.89] respectively. Cohen's Kappa coefficients were
      0.78 [0.72, 0.84] for stroke and 0.80 [0.76, 0.84] for coronary deaths. In
      addition to female gender and increasing age at death, cerebral stroke was a
      negative predictor of an autopsy being carried out (odds ratio (OR) 0.69, 95% CI
      [0.54, 0.87]), whereas death from coronary heart disease was not (OR 1.14, 95% CI
      [0.97, 1,33]), both adjusted for gender and age at death. There was substantial
      agreement between mortality statistics and autopsy findings for both fatal
      strokes and coronary deaths. Selection for post mortem examinations was
      associated with age, gender and cause of death.

PMID- 21170573
TI  - Synthesis of CaO-SiO2-P2O5 mesoporous bioactive glasses with high P2O5 content by
      evaporation induced self assembly process.
AB  - Mesoporous bioactive glasses (MBGs) of the CaO-SiO(2)-P(2)O(5) system containing
      relatively high P(2)O(5) contents (10-30 mol%) were prepared from a sol-gel. An
      evaporation-induced self-assembly (EISA) technique was used with poly(ethylene
      oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (EO(20)-PO(70)
      EO(20), P123) acting as a template. The structural, morphological and textural
      properties of MBGs were investigated by small-angle X-ray diffraction (SAXRD),
      transmission electron microscopy (TEM), Fourier transform infrared (FTIR)
      spectroscopy and a N(2) sorption/desorption technique. SAXRD and TEM results
      display the reduced long-range ordering of mesopores with increasing P(2)O(5)
      content. N(2) sorption/desorption analysis shows that all three samples exhibit a
      type IV isotherm with type H1 hysteresis loops, characteristic of independent
      cylindrical slim pore channels and this material has a Barret-Joyner-Halenda
      (BJH) model pore size of ~4 nm and BET specific surface area ~430 m(2)/g. NMR
      results indicate a more condensed framework for samples with 30 mol% P(2)O(5)
      than samples with 10 mol% P(2)O(5). For in vitro bioactivity tests where samples
      were soaked in simulated body fluid (SBF), samples with 30 mol% P(2)O(5) showed
      higher crystallinity than those with lower P(2)O(5) contents Silicon
      concentration increased in SBF solution during the soaking period, which
      indicates MBGs can be degradable in SBF solution.

PMID- 21170575
TI  - Eliciting cues to false intent: a new application of strategic interviewing.
AB  - This article examined how to elicit cues to deception when a suspect is asked
      both about his/her intentions and his/her corresponding past planning, and when
      the investigator holds evidence on the suspect's planning activities. In a new
      experimental set-up accommodating the main characteristics of intent,
      participants (N = 120) either planned a criminal or a non-criminal act. They were
      intercepted before completing the planned act. Each participant was interviewed
      in accordance with one of three interview techniques: Early Evidence disclosure
      or one of two versions of the Strategic Use of Evidence (SUE) technique. All the
      interviews were transcribed and scored for consistency. As predicted, the liars
      were perceived as having a higher degree of inconsistency for two of the three
      relevant comparisons (Statement on Planning-Evidence on Planning; Statement on
      Intent-Evidence on Planning). Furthermore, using the evidence strategically
      resulted in differences between liars and truth tellers being magnified, as
      predicted. This article advances previous findings in showing that by
      interviewing strategically with respect to the evidence, it is possible to elicit
      reliable cues to deception when a suspect is asked about intentions and
      corresponding planning activities.

PMID- 21170574
TI  - Type of alcohol drink and exposure to violence: an emergency department study.
AB  - We compared the prevalence of exposure to violence across different types of
      alcohol consumed and the association between the type of alcohol consumed and
      exposure to violence. A cross-sectional analysis of data collected from a sample
      of 295 Emergency Department (ED) patients identified as having an alcohol
      problem. Outcome measure include exposure to violence, and the main study
      predictor was "type of alcoholic drink" including: malt liquor beer (MLB),
      regular beer, wine cooler, wine, fortified wine or hard liquor. Using logistic
      regression analysis, ED patients who drank MLB in combination with other types of
      alcohol increased their odds of being both threatened and physically attacked by
      8.5 compared to ED patients who drank other types of alcohol. Being female
      increased the odds of being both threatened and physically attacked by 2.5 and
      using illicit drugs increased the odds by 3.8. Analysis of covariance and
      estimated marginal means revealed that ED patients who only drank MLB had a
      higher exposure to violence compared to non-MLB drinkers, and that female illicit
      drug users who drank MLB in combination with other types of alcohol had the
      highest exposure to violence. MLB was identified as a predictor of the amount of
      exposure to violence and in particular, that the use of malt liquor beer in
      combination with other types of alcohol increased the risk of being both
      threatened and physically attacked. Implications for ED and community
      interventions are suggested.

PMID- 21170576
TI  - The repeated appeal to return home in older adults with dementia: developing a
      model for practice.
AB  - Dementia care has been trapped in a "trial and error" type of practice due to
      difficulty understanding the needs of older adults with severe dementia.
      Behavioral and Psychological Signs and Symptoms of Dementia (BPSD) can be quite
      difficult for residential staff. However, some experienced care workers succeed
      in establishing effective relationships. The goal of this study was to: 1)
      develop a process to identify needs behind BPSD; 2) find solutions using a team
      approach; and 3) apply the results to educate new workers. The KJ method was
      employed to reach decision-making about best practices in residential dementia
      care. This qualitative method is used to organize group data collected in the
      field and is based on understanding complex situations. A group process of 12
      Japanese care workers experienced in understanding and responding to the
      "repeated appeal to return home" of residents in nursing care facilities is
      highlighted along with an illustrative case example. The workgroup met over two
      years. The study revealed five steps in understanding the needs behind the
      appeal, which include: (1) Listen to the voice and go with the flow of the
      behavior; (2) Learn about the inner experience; (3) Learn about the contextual
      environment of "here and now" situations; (4) Reflect on the care environment;
      and (5) Find the keyword. This needs identification process has application to
      other cultural contexts. The implications of this study for practitioners who
      work with people with dementia in residential settings will be discussed.

PMID- 21170577
TI  - Neural adaptation facilitates oscillatory responses to static inputs in a
      recurrent network of ON and OFF cells.
AB  - We investigate the role of adaptation in a neural field model, composed of ON and
      OFF cells, with delayed all-to-all recurrent connections. As external spatially
      profiled inputs drive the network, ON cells receive inputs directly, while OFF
      cells receive an inverted image of the original signals. Via global and delayed
      inhibitory connections, these signals can cause the system to enter states of
      sustained oscillatory activity. We perform a bifurcation analysis of our model to
      elucidate how neural adaptation influences the ability of the network to exhibit
      oscillatory activity. We show that slow adaptation encourages input-induced
      rhythmic states by decreasing the Andronov-Hopf bifurcation threshold. We further
      determine how the feedback and adaptation together shape the resonant properties
      of the ON and OFF cell network and how this affects the response to time-periodic
      input. By introducing an additional frequency in the system, adaptation alters
      the resonance frequency by shifting the peaks where the response is maximal. We
      support these results with numerical experiments of the neural field model.
      Although developed in the context of the circuitry of the electric sense, these
      results are applicable to any network of spontaneously firing cells with global
      inhibitory feedback to themselves, in which a fraction of these cells receive
      external input directly, while the remaining ones receive an inverted version of
      this input via feedforward di-synaptic inhibition. Thus the results are relevant
      beyond the many sensory systems where ON and OFF cells are usually identified,
      and provide the backbone for understanding dynamical network effects of lateral
      connections and various forms of ON/OFF responses.

PMID- 21170578
TI  - HPV testing for cervical cancer screening appears more cost-effective than
      Papanicolau cytology in Mexico.
AB  - OBJECTIVE: To determine the incremental costs and effects of different HPV
      testing strategies, when compared to Papanicolau cytology (Pap), for cervical
      cancer screening in Mexico. METHODS: A cost-effectiveness analysis (CEA) examined
      the specific costs and health outcomes associated with (1) no screening; (2) only
      the Pap test; (3) only self-administered HPV; (4) only clinician administered
      HPV; and (5) clinician administered HPV plus the Pap test. The costs of self- and
      clinician-HPV testing, as well as with the Pap test, were identified and
      quantified. Costs were reported in 2008 US dollars. The health outcome associated
      with these screening strategies was defined as the number of high-grade cervical
      intraepithelial neoplasia or cervical cancer cases detected. This CEA was
      performed using the perspective of the Mexican Institute of Social Security
      (IMSS) in Morelos, Mexico. RESULTS: Screening women between the ages of 30-80 for
      cervical cancer using clinical-HPV testing or the combination of clinical-HPV
      testing, and the Pap is always more cost-effective than using the Pap test alone.
      CONCLUSIONS: This CEA indicates that HPV testing could be a cost-effective
      screening alternative for a large health delivery organization such as IMSS.
      These results may help policy-makers implement HPV testing as part of the IMSS
      cervical cancer screening program.

PMID- 21170579
TI  - Expression of biologically active human interferon gamma in the milk of
      transgenic mice under the control of the murine whey acidic protein gene
      promoter.

PMID- 21170580
TI  - Protective effects of flavonoid extract from Apocynum venetum leaves against
      corticosterone-induced neurotoxicity in PC12 cells.
AB  - Depression is a major psychiatric disorder affecting nearly 21% of the world
      population and imposes a substantial health burden on society. Although
      significant progress has been made in depression research, the common molecular
      mechanism of antidepressants is still far from clearly understood. The
      neuroprotective effect of antidepressants has been proposed as a possible
      mechanism. Although Apocynum venetum (AV) L. (Apocynaceae) was previously shown
      to produce an antidepressant-like effect in the tail suspension test, the
      mechanisms underlying such antidepressant-like effect are yet to be understood.
      In this work, we studied the neuroprotective effect of AV leaf flavonoid extract
      in corticosterone-induced neurotoxicity, using PC12 cells as a suitable in vitro
      model of depression. Cell viability was quantitated by 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The release amount of lactic
      dehydrogenase (LDH) and intracellular Ca(2+) concentration were measured using
      kit, cell period change was tested by flow cytometry, and transcript abundances
      of brain-derived neurotrophic factor (BDNF) and microtubule-associated protein 4
      (MAP4) were determined by real-time RT-PCR. The results showed that AV extract
      (25, 50, and 100 MUg/ml) increased the A490 nm values, but decreased LDH release
      and Ca(2+) concentration, suppressed the apoptosis of PC12 cells and up-regulated
      BDNF and MAP4 transcript abundances compared with the corresponding
      corticosterone-treated group. These results suggest that the AV extract could
      generate a neuroprotective effect on corticosterone-induced neurotoxicity in PC12
      cells, pointing to a possible action pathway by decreasing the Ca(2+)
      concentration and up-regulating BDNF and MAP4 genes.

PMID- 21170582
TI  - A uniform fish consumption advisory protocol for the Ohio River.
AB  - ORSANCO and the six Ohio River main stem states have been working to align
      states' fish consumption advisories (FCAs) to enhance the value of advice issued
      to the public. To achieve this goal, ORSANCO worked closely with a panel
      consisting of state and USEPA representatives. The result of this effort is the
      Ohio River Fish Consumption Advisory Protocol (ORFCAP). The ORFCAP represents a
      single set of variables agreed upon by the panel that allows for a standardized
      protocol to create advisory thresholds to which states can defer to issue
      consumption advice for the Ohio River. The ORFCAP identifies ORSANCO as a
      clearinghouse for data which will be distributed to the panel for decision
      making. Other components include identifying primary contaminants of concern
      (PCBs and mercury) and dividing the river into four reporting units. The protocol
      was developed to issue FCAs for the protection of sensitive populations using
      five advisory groupings for PCBs and four for mercury. Specific variables used in
      the calculation of advisory thresholds such as health protection values, cooking
      reductions, average meal sizes, etc., were selected by the panel. Lastly, the
      protocol calls for FCA decisions to be based on analysis of the most recent 10
      years of data for each species in each reporting unit to determine size class
      needs and advisory groupings. Upon pending implementation of the protocol by the
      main stem states, these decisions will be made annually through a series of
      discussions involving ORSANCO, the panel, and other appropriate state personnel.

PMID- 21170581
TI  - Beneficial effects of folic acid on enhancement of memory and antioxidant status
      in aged rat brain.
AB  - As our population ages, diseases affecting memory and daily functioning will
      affect an increasing number of individuals, their families and the healthcare
      system. Therefore, there is a need to study and evaluate effects of certain
      conditions for anti-aging of the brain. Nutrient supplementation can modify the
      brain function. The chemistry and function of both the developing and the mature
      brain are influenced by diet (Fernstrom, Am J Clinical Nutrition 71:1669S-1673S,
      2000). Clinical, biochemical, and pathological aspects have shown a correlation
      between mental symptoms, especially depression and cognitive decline, with high
      incidence of folate deficiency (Bottiglieri et al., J Neurol Neurosurg Psychiatry
      69:562, 2000). In the present study, consequences of folic acid supplementation
      on brain dysfunction as a result of aging were studied in cerebral cortex, mid
      brain, and cerebellar regions of rat brain. This study was carried out on 6-, 11
      , and 16-month-old rats, which received folic acid at a dose of 5 mg/kg body
      weight/day for a period of 8 weeks. Respective control groups of the same age
      groups were also taken. At the end of the treatment duration, behavioral studies
      were performed and later the animals were killed for various biochemical and
      histological investigations. Results indicated significant improvement in memory
      as assessed by active avoidance, passive avoidance, and plus maze tests in the
      folic acid supplemented aged animals. Significant improvement was also seen in
      the cellular protective mechanisms where by the activity of superoxide dismutase
      and catalase enzymes increased in folic acid supplemented group and so was the
      glutathione content. Increased lipid peroxidation content, a marker of aging, was
      also found to be decreased during folic acid supplementation in all the three
      regions of brain in our study. Thus, it can be concluded that folic acid helps in
      improving the memory status by reducing oxidative stress and maintaining the
      integrity of neurons during aging.

PMID- 21170583
TI  - Natural factors and mining activity bearings on the water quality of the Choapa
      basin, North Central Chile: insights on the role of mafic volcanic rocks in the
      buffering of the acid drainage process.
AB  - This contribution analyzes water chemical data for the Choapa basin, North
      Central Chile, for the period 1980-2004. The parameters considered are As, Cu Fe,
      pH, EC, SO4-2, Cl-1, and HCO[Formula: see text], from samples taken in nine
      monitoring stations throughout the basin. Results show rather moderate contents
      of As, Cu, and Fe, with the exception of the Cuncumen River and the Auco creek,
      explained by the influence of the huge porphyry copper deposit of Los Pelambres
      and by the presence of mining operations, respectively. When compared against
      results obtained in previous researches at the neighboring Elqui river basin,
      which host the El Indio Au-Cu-As district, a much reduced grade of pollution is
      recognized for the Choapa basin. Considering the effect of acid rock drainage
      (ARD)-related Cu contents on the fine fraction of the sediments of both river
      basins, the differences recorded are even more striking. Although the Los
      Pelambres porphyry copper deposit, on the headwaters of the Choapa river basin,
      is between one and two orders of magnitude bigger than El Indio, stream water and
      sediments of the former exhibit significantly lower copper contents than those of
      the latter. A main factor which may explain these results is the smaller degree
      of H( + )-metasomatism on the host rocks of the Los Pelambres deposit, where
      mafic andesitic volcanic rocks presenting propylitic hydrothermal alteration are
      dominant. This fact contrast with the highly altered host rocks of El Indio
      district, where most of them have lost their potential to neutralize ARD.

PMID- 21170584
TI  - WEPP and ANN models for simulating soil loss and runoff in a semi-arid
      Mediterranean region.
AB  - This paper presents the use of both the Water Erosion Prediction Project (WEPP)
      and the artificial neural network (ANN) for the prediction of runoff and soil
      loss in the central highland mountainous of the Palestinian territories. Analyses
      show that the soil erosion is highly dependent on both the rainfall depth and the
      rainfall event duration rather than on the rainfall intensity as mostly mentioned
      in the literature. The results obtained from the WEPP model for the soil loss and
      runoff disagree with the field data. The WEPP underestimates both the runoff and
      soil loss. Analyses conducted with the ANN agree well with the observation. In
      addition, the global network models developed using the data of all the land use
      type show a relatively unbiased estimation for both runoff and soil loss. The
      study showed that the ANN model could be used as a management tool for predicting
      runoff and soil loss.

PMID- 21170586
TI  - Anemia at one year is an independent risk factor of graft survival.
AB  - BACKGROUND: Post-transplant anemia is multifactorial and highly prevalent. Some
      studies have associated anemia with mortality and graft failure. The purpose of
      this study was to assess whether the presence of anemia at 1 year is an
      independent risk factor of mortality and graft survival. METHODS: All patients
      transplanted at a single center who survived at least 1 year after
      transplantation and showed no graft loss (n = 214) were included. Demographic and
      clinical data were collected at baseline and at 1 year. Patients were divided
      into two groups (anemic and nonanemic) based on the presence of anemia
      (hemoglobin < 130 g/l in men and 120 g/l in women). RESULTS: Baseline
      characteristics such as age, gender, type of donor, CKD etiology, rejection, and
      mismatches were similar in both groups. Creatinine clearance was similar in both
      anemic and nonanemic groups (69.32 +/- 29.8 * 75.69 +/- 30.5 ml/mim; P = 0.17). A
      Kaplan-Meier plot showed significantly poorer death-censored graft survival in
      the anemic group, P = 0.003. Multivariate analysis revealed that anemic patients
      had a hazard ratio for the graft loss of 3.85 (95% CI: 1.49-9.96; P = 0.005).
      CONCLUSIONS: In this study, anemia at 1 year was independently associated with
      death-censored graft survival and anemic patients were 3.8-fold more likely to
      lose the graft.

PMID- 21170585
TI  - The role of cardiac magnetic resonance imaging in the assessment of non-ischemic
      cardiomyopathy.
AB  - Cardiovascular magnetic resonance imaging (CMR) plays an increasing role in the
      assessment of patients with various cardiovascular disorders. Given its enhanced
      spatial resolution, improved tissue characterization, and lack of ionizing
      radiation, it has become the test of choice in the evaluation of patients with
      new-onset cardiomyopathy of unknown etiology. In this paper, we will review the
      role of CMR in the evaluation of patients with various types of non-ischemic
      cardiomyopathy.

PMID- 21170588
TI  - English language proficiency and geographical proximity to a safety net clinic as
      a predictor of health care access.
AB  - Studies suggest that proximity to a safety net clinic (SNC) promotes access to
      care among the uninsured. Distance-based barriers to care may be greater for
      people with limited English proficiency (LEP), compared to those who are English
      proficient (EP), but this has not been explored. We assessed the relationship
      between distance to the nearest SNC and access in non-rural uninsured adults in
      California, and examined whether this relationship differs by language
      proficiency. Using the 2005 California Health Interview Survey and a list we
      compiled of California's SNCs, we calculated distance between uninsured
      interviewee residence and the exact address of the nearest SNC. Using
      multivariate regression to adjust for other relevant characteristics, we examined
      associations between this distance and interviewee's probability of having a
      usual source of health care (USOC) and having visited a physician in the prior 12
      months. To examine differences by language proficiency, we included interactions
      between distance and language proficiency. Uninsured LEP adults living within 2
      miles of a SNC were 9.3% less likely than their EP counterparts to have a USOC (P
      = 0.046). Further, distance to the nearest SNC was inversely associated with the
      probability of having a USOC among LEP, but not among EP; consequently, the
      difference between LEP and EP in the probability of having a USOC widened with
      increasing distance to the nearest SNC. There was no difference between LEP and
      EP adults living within 2 miles of a SNC in likelihood of having a physician
      visit; however, as with USOC, distance to the nearest SNC was inversely
      associated with the probability of having a physician visit among LEP but not EP.
      The effect sizes diminished, but remained significant, when we included county
      fixed effects in the models. Having LEP is a barrier to health care access, which
      compounds when combined with increased distance to the nearest SNC, among
      uninsured adults. Future studies should explore potential mechanisms so that
      appropriate interventions can be implemented.

PMID- 21170589
TI  - Child and parental outcomes following involvement in a preventive intervention:
      efficacy of the PACE program.
AB  - This study evaluated whether engagement (i.e., attendance and quality of
      participation) in the Parenting our Children to Excellence (PACE) program
      predicted positive child and parent outcomes. PACE in an 8-week preventive
      intervention aimed at parents of preschool children. The study investigated the
      relation of engagement to outcomes in an ethnically diverse sample of 610 parents
      and among a subset of those parents at high risk for child maltreatment. Overall
      results demonstrated that engagement in PACE significantly improved child and
      parent outcomes at post-assessment and/or one-year follow-up assessment. Results
      for the high-risk subsample were even stronger as engagement significantly
      improved almost all of the child and parent outcomes at post-assessment, which
      continued to significantly improve in the year following program completion.
      Findings provide support for the efficacy of PACE in improving child and parent
      outcomes in an ethnically diverse community population and among parents
      considered at risk for child maltreatment.

PMID- 21170590
TI  - Betanodavirus up-regulates chaperone GRP78 via ER stress: roles of GRP78 in viral
      replication and host mitochondria-mediated cell death.
AB  - Whether viral pathogens that induce ER stress responses benefit the host or the
      virus remains controversial. In this study we show that betanodavirus induced ER
      stress responses up-regulate GRP78, which regulates the viral replication and
      host cellular mitochondrial-mediated cell death. Betanodavirus (redspotted
      grouper nervous necrosis virus, RGNNV) infection resulted in the following
      increased ER stress responses in fish GF-1 grouper fin cells: (1) IRE-1 and ATF-6
      sensors at 48 h post-infection (p.i.) that up-regulated chaperone protein GRP78;
      (2) activation of caspase-12; and (3) PERK phosphorylation and down-regulation of
      Bcl-2. Analyses of GRP78 functions during viral replication using either loss-of
      function or gain-of-function approaches showed that GRP78 over-expression also
      enhanced viral replication and induced cell death. Then, we found that zfGRP78
      localization gradually increased in mitochondria after RGNNV infection by EGFP
      tagging approach. Furthermore, zfGRP78 can interact with viral RNA-dependent RNA
      polymerase (RdRp) by using immunofluorescent and immunoprecipitation assays.
      Finally, we found that blocking GRP78-mediated ER signals can reduce the viral
      death factors protein alpha and protein B2 expression and decrease the Bcl-2 down
      regulation mediated mitochondria-dependent cell death, which also enhances host
      cellular viability. Taken together, our results suggest that RGNNV infection and
      expression can trigger ER stress responses, which up-regulate the chaperone GRP78
      at early replication stage. Then, GRP78 can interact with RdRp that may enhance
      the viral replication for increasing viral death factors' expressions at middle
      late replication stage, which can enhance mitochondrial-mediated cell death
      pathway and viral spreading. These results may provide new insights into the
      mechanism of ER stress-mediated cell death in RNA viruses.

PMID- 21170592
TI  - A field effect transistor (FET)-based immunosensor for detection of HbA1c and Hb.
AB  - A field effect transistor (FET)-based immunosensor was developed for diabetes
      monitoring by detecting the concentrations of glycated hemoglobin (HbA1c) and
      hemoglobin (Hb). This immunosensor consists of a FET-based sensor chip and a
      disposable extended-gate electrode chip. The sensor chip was fabricated by
      standard CMOS process and was integrated with signal readout circuit. The
      disposable electrode chip, fabricated on polyester plastic board by Micro-Electro
      Mechanical-Systems (MEMS) technique, was integrated with electrodes array and
      micro reaction pool. Biomolecules were immobilized on the electrode based on self
      assembled monolayer and gold nanoparticles. Experimental results showed that the
      immunosensor achieved a linear response to HbA1c with the concentration from 4 to
      24 MUg/ml, and a linear response to Hb with the concentration from 60 to 180
      MUg/ml.

PMID- 21170591
TI  - Functional analysis by 64-slice CT scanning: prediction of left ventricular
      dysfunction together with reduction in radiation exposure?

PMID- 21170593
TI  - 17 beta-estradiol attenuates pressure overload-induced myocardial hypertrophy
      through regulating caveolin-3 protein in ovariectomized female rats.
AB  - Our findings indicate that in ovariectomized female rats abdominal aortic
      constriction led to significant increases in left ventricular mass, myocyte
      diameter and heart weight/body weight (HW/BW) value, and decreases in
      interventricular septal thickness at diastole (IVSd), left ventricular percent
      fractional shortening (FS) and ejection fraction (EF). These pathophysiological
      alterations were largely reversed by administration with 17beta-estradiol for
      eight weeks. Furthermore, the enhanced expression of extracellular signal
      regulated kinases 1/2 and decreased expression of caveolin-3 were found in left
      ventricle of AAC group. 17beta-estradiol (E(2)) administration increased the
      expression of caveolin-3 and reduced the level of ERK phosphorylation in these
      pressure-overloaded rats. Moreover, in cultured neonatal rat cardiomyocytes, E(2)
      inhibited the hypertrophic response to angiotensin II. This effect was reinforced
      by the addition of extracellular signal-regulated kinases 1/2 inhibitor PD98059,
      but was impaired when the cells were pretreated with caveolae disruptor, methyl
      beta-cyclodextrin (M-beta-CD). In conclusion, our data indicate that estrogen
      attenuates the hypertrophic response induced by pressure overload through down
      regulation of extracellular signal-regulated kinases 1/2 phosphorylation and up
      regulation of caveolin-3 expression.

PMID- 21170595
TI  - Frequency of acromegaly in adults with diabetes or glucose intolerance and
      estimated prevalence in the general population.
AB  - The objective of this study was to evaluate the frequency of acromegaly in adults
      with diabetes mellitus (DM) or glucose intolerance (GI) and to estimate its
      prevalence in the general population. A total of 2,270 patients with DM or GI and
      age from 20 to 70 years were studied. Patients with known pituitary disease and
      pregnant women were excluded. Serum IGF-1 was measured in all subjects and, if
      elevated, a new measurement was obtained together with the measurement of GH in
      the oral glucose tolerance test (OGTT). Patients with persistently elevated IGF-1
      and inadequate suppression of GH were submitted to magnetic resonance imaging
      (MRI). Acromegaly was not suspected by the assistant physician in any of the
      patients. Six patients had persistently elevated IGF-1 and inadequate suppression
      of GH in the OGTT (without other conditions associated with GH or IGF-1
      elevation). Pituitary adenoma was detected by MRI in three patients, and two
      subjects presented an acromegalic phenotype. Two patients were submitted to
      transsphenoidal surgery, with immunohistochemistry confirming immunoreactivity
      for GH. Another patient was treated with octreotide LAR which resulted in the
      normalization of IGF-1 and GH. Considering a prevalence of DM or GI of 20% in
      adults and the occurrence of these co-morbidities in 55% of patients with
      acromegaly, the frequency of 3/2,270 found in this study permits to estimate 480
      cases/1,000,000 adults. The present results suggest that the prevalence of
      acromegaly is underestimated and further studies are needed to evaluate the cost
      effectiveness of biochemical screening in certain groups of patients.

PMID- 21170594
TI  - Pituitary surgery for small prolactinomas as an alternative to treatment with
      dopamine agonists.
AB  - Despite the fact that consensus guidelines recommend long-term dopamine agonist
      (DA) therapy as a first-line approach to the treatment of small prolactinoma,
      some patients continue to prefer a primary surgical approach. Concerns over
      potential adverse effects of long-term medical therapy and/or the desire to
      become pregnant and avoid long-term medication are often mentioned as reasons to
      pursue surgical removal. In this retrospective study, 34 consecutive patients (30
      female, 4 male) preferably underwent primary pituitary surgery without prior DA
      treatment for small prolactinomas (microprolactinoma 1-10 mm, macroprolactinoma
      11-20 mm) at the Department of Neurosurgery, University of Bern, Switzerland. At
      the time of diagnosis, 31 of 34 patients (91%) presented with symptoms. Patients
      with microprolactinomas had significantly lower preoperative prolactin (PRL)
      levels compared to patients with macroprolactinomas (median 143 MUg/l vs. 340
      MUg/l). Ninety percent of symptomatic patients experienced significant
      improvement of their signs and symptoms upon surgery. The postoperative PRL
      levels (median 3.45 MUg/l) returned to normal in 94% of patients with small
      prolactinomas. There was no mortality and no major morbidities. One patient
      suffered from hypogonadotropic hypogonadism after surgery despite postoperative
      normal PRL levels. Long-term remission was achieved in 22 of 24 patients (91%)
      with microprolactinomas, and in 8 of 10 patients (80%) with macroprolactinomas
      after a median follow-up period of 33.5 months. Patients with small prolactinomas
      can safely consider pituitary surgery in a specialized centre with good chance of
      long-term remission as an alternative to long-term DA therapy.

PMID- 21170598
TI  - Analysis of discrete bioregulatory networks using symbolic steady states.
AB  - A discrete model of a biological regulatory network can be represented by a
      discrete function that contains all available information on interactions between
      network components and the rules governing the evolution of the network in a
      finite state space. Since the state space size grows exponentially with the
      number of network components, analysis of large networks is a complex problem. In
      this paper, we introduce the notion of symbolic steady state that allows us to
      identify subnetworks that govern the dynamics of the original network in some
      region of state space. We state rules to explicitly construct attractors of the
      system from subnetwork attractors. Using the results, we formulate sufficient
      conditions for the existence of multiple attractors resp. a cyclic attractor
      based on the existence of positive resp. negative feedback circuits in the graph
      representing the structure of the system. In addition, we discuss approaches to
      finding symbolic steady states. We focus both on dynamics derived via synchronous
      as well as asynchronous update rules. Lastly, we illustrate the results by
      analyzing a model of T helper cell differentiation.

PMID- 21170597
TI  - Statistical analysis and isotherm study of uranium biosorption by Padina sp.
      algae biomass.
AB  - INTRODUCTION: The application of response surface methodology is presented for
      optimizing the removal of U ions from aqueous solutions using Padina sp., a brown
      marine algal biomass. METHODS: Box-Wilson central composite design was employed
      to assess individual and interactive effects of the four main parameters (pH and
      initial uranium concentration in solutions, contact time and temperature) on
      uranium uptake. RESULTS AND DISCUSSION: Response surface analysis showed that the
      data were adequately fitted to second-order polynomial model. Analysis of
      variance showed a high coefficient of determination value (R (2)=0.9746) and
      satisfactory second-order regression model was derived. CONCLUSION: The optimum
      pH and initial uranium concentration in solutions, contact time and temperature
      were found to be 4.07, 778.48 mg/l, 74.31 min, and 37.47 degrees C, respectively.
      Maximized uranium uptake was predicted and experimentally validated. The
      equilibrium data for biosorption of U onto the Padina sp. were well represented
      by the Langmuir isotherm, giving maximum monolayer adsorption capacity as high as
      376.73 mg/g.

PMID- 21170599
TI  - Stapling technique for performing Billroth II anastomosis after distal
      gastrectomy.
AB  - The circular stapling technique has been widely applied for gastrointestinal
      anastomosis in gastrectomies (open or laparoscopic) for distal gastric cancers.
      We describe this method for use in performing Billroth II anastomosis in distal
      gastrectomies. From 2002-2009, we report the results following the use of the
      circular stapling technique performed in 520 patients at a single institution.
      The median time of completing the anastomosis was shorter using the stapling
      technique compared to the hand-sewn technique. The use of the stapler resulted in
      two cases of minor intraluminal bleeding at the anastomotic site. The circular
      stapling method can be applied safely and more efficiently in performing Billroth
      II reconstruction after distal gastrectomy compared to the hand-sewn method in
      patients with gastric cancer.

PMID- 21170600
TI  - Improvement of respiratory symptoms following Heller myotomy for achalasia.
AB  - INTRODUCTION: Although patients with achalasia complain mainly of dysphagia, we
      have observed that they also have a high rate of respiratory problems. We
      hypothesized that the latter may be due to poor esophageal clearance leading to
      aspiration. This study examines the effect of Heller myotomy on these symptoms.
      METHODS: We studied the course of 111 patients with achalasia who underwent
      Heller myotomy between 1994 and 2008 and who agreed to participate in this study.
      All patients completed a questionnaire postoperatively assessing the preoperative
      and postoperative prevalence and severity of symptoms using visual analog scales.
      Patients were divided into two groups: one that included all those with
      respiratory symptoms (dyspnea, hoarseness, cough, wheezing, sore throat, and/or a
      history of asthma or pneumonia) prior to myotomy and one that included those
      without those symptoms. RESULTS: All patients presented with dysphagia as their
      primary complaint, and 63 (57%) reported respiratory symptoms or disease prior to
      surgery. There were no significant differences in preoperative characteristics
      between those with and without respiratory manifestations. After a median follow
      up of 71 months (range 9-186 months), 55 (87%) patients reported durable
      improvement of dysphagia. The frequency and severity of all respiratory symptoms
      decreased significantly. Twenty-four of the 29 patients (82%) who reported a
      history of pneumonia prior to surgery did not experience recurrent episodes after
      Heller myotomy. CONCLUSIONS: A Heller myotomy is effective in improving
      esophageal emptying in patients with achalasia. This results in sustained
      improvement of dysphagia and associated respiratory symptoms/diseases. This
      suggests that respiratory symptoms/diseases in these patients are likely caused
      by esophageal retention of food and secretions, and then aspiration.

PMID- 21170601
TI  - Intestinal adaptation for oligopeptide absorption via PepT1 after massive (70%)
      mid-small bowel resection.
AB  - INTRODUCTION: Proteins are absorbed primarily as short peptides via peptide
      transporter 1 (PepT1). HYPOTHESIS: Intestinal adaptation for peptide absorption
      after massive mid-small intestinal resection occurs by increased expression of
      PepT1 in the remnant small intestine and colon. METHODS: Peptide uptake was
      measured in duodenum, jejunum, ileum, and colon using glycyl-sarcosine 1 week (n
      = 9) and 4 weeks (n = 11) after 70% mid-small bowel resection and in
      corresponding segments from unoperated rats (n = 12) and after transection and
      reanastomosis of jejunum and ileum (n = 8). Expression of PepT1 (mRNA, protein)
      and villus height were measured. RESULTS: Intestinal transection/reanastomosis
      did not alter gene expression. Compared to non-operated controls, 70% mid-small
      bowel resection increased jejunal peptide uptake (p < 0.05) associated with
      increased villus height (1.13 vs 1.77 and 1.50 mm, respectively, p < 0.01). In
      ileum although villus height increased at 1 and 4 weeks (1.03 vs 1.21 and 1.35
      mm, respectively; p < 0.01), peptide uptake was not altered. PepT1 mRNA and
      protein were decreased at 1 week, and PepT1 protein continued low at 4 weeks.
      Gene expression, peptide uptake, and histomorphology were unchanged in the colon.
      CONCLUSIONS: Jejunal adaptation for peptide absorption occurs by hyperplasia.
      Distal ileum and colon do not have a substantive role in adaptation for peptide
      absorption.

PMID- 21170602
TI  - Effects of chronic boron exposure on semen profile.
AB  - The possible changes in semen quality were studied in men living in a boron
      mining area. The subjects in the boron group had exposure to boron at an average
      level of 6.5 mg/day, as determined by urinary analysis. The results obtained by
      the boron group were compared to those obtained for the control group whose
      subjects were living in the same geographical area but away from the boron
      region; average exposure level was 1.4 mg/day for this group. The semen samples
      were analyzed according to the recommendations of the World Health Organization.
      Boron levels were established in the water samples obtained from various
      locations in the study region. In the boron mining fields where the subjects in
      the boron group live, water samples contained boron in the range of 1.4-6.5 mg/L,
      while the values were <0.01 mg/L for the water samples obtained from the region
      where the subjects of the control group reside. No negative effects were found in
      the sperm samples obtained from the subjects of the boron group.

PMID- 21170603
TI  - Effects of chromium brewer's yeast supplementation on body mass, blood
      carbohydrates, and lipids and minerals in type 2 diabetic patients.
AB  - Chromium(III) is considered as an essential element for carbohydrate and lipid
      metabolism. The aim of this clinical study was to evaluate the efficacy of Cr
      brewer's yeast supplementation on body mass, carbohydrate, lipids and mineral
      indices in type 2 diabetic patients. Twenty adult type 2 diabetic subjects (11
      males and 9 females aged 37-63) were supplemented with Cr brewer's yeast in
      dosages of 500 MUg Cr/person/day or placebo for 8 weeks in a double-blind,
      placebo-controlled crossover design. It was found that supplemental Cr did not
      affect body mass, blood lipid profile, resistin levels, and the serum and hair
      Zn, Fe, and Cu levels, but increased serum Cr (by 116%) and hair Cr (by 20.6%)
      concentrations and improved some blood carbohydrate indices (significant increase
      in the beta cell function index by 18.8%) in type 2 diabetic patients. In
      conclusion, Cr brewer's yeast has a weak hypoglycemic potential, but does not
      affect body mass, blood biochemical profile, and microelement levels in type 2
      diabetic subjects.

PMID- 21170604
TI  - Three alginate lyases from marine bacterium Pseudomonas fluorescens HZJ216:
      purification and characterization.
AB  - Three alginate lyases (A, B, and C) from an alginate-degrading marine bacterium
      strain HZJ216 isolated from brown seaweed in the Yellow Sea of China and
      identified preliminarily as Pseudomonas fluorescens are purified, and their
      biochemical properties are described. Molecular masses of the three enzymes are
      determined by SDS-PAGE to be 60.25, 36, and 23 kDa with isoelectric points of 4,
      4.36, and 4.59, respectively. Investigations of these enzymes at different pH and
      temperatures show that they are most active at pH 7.0 and 35  degrees C. Alginate
      lyases A and B are stable in the pH range of 5.0-9.0, while alginate lyase C is
      stable in the pH range of 5.0-7.0. Among the metal ions tested, additions of
      Na(+), K(+), and Mg(2+) ions can enhance the enzyme activities while Fe(2+),
      Fe(3+), Ba(2+), and Zn(2+) ions show inhibitory effects. The substrate
      specificity results demonstrate that alginate lyase C has the specificity for G
      block while alginate lyases A and B have the activities for both M and G blocks.
      It is the first report about extracellular alginate lyases with high alginate
      degrading activity from P. fluorescens.

PMID- 21170605
TI  - Cutting edge issues in primary sclerosing cholangitis.
AB  - Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease
      characterized by the destruction of medium- to large-sized bile ducts and intense
      concentric fibrosis. Complications from PSC include bacterial cholangitis,
      cirrhosis, and cholangiocarcinoma and a therapy that might alter the natural
      history of the disease remains lacking. Our understanding of the pathogenesis of
      PSC also remains rudimentary but the strong association between PSC and
      inflammatory bowel disease suggest causal links between the diseases. The male
      predominance in PSC, lack of a defined, pathogenic auto-antigen, and the
      potential role of the innate immune system suggest that PSC may be due to
      dysregulation of immunity rather than a classic autoimmune disease. However, PSC
      shares several genetic susceptibility loci with other autoimmune diseases
      including the human leukocyte antigen DRB01*03 haplotype. The precise immune
      response of PSC is largely unknown but likely involves activation of the innate
      immune system by bacterial components delivered to the liver via the portal vein.
      Induction of adhesion molecules and chemokines leads to the recruitment of
      intestinal lymphocytes. Bile duct injury results from the sustained inflammation
      and production of inflammatory cytokines. Biliary strictures may cause further
      damage as a result of bile stasis and recurrent secondary bacterial cholangitis.
      Progress in our basic understanding of PSC is desperately needed in order to
      rationally design new therapeutic approaches to this disease.

PMID- 21170606
TI  - Role of autoimmunity and autoinflammation in the pathogenesis of idiopathic
      recurrent pericarditis.
AB  - Idiopathic recurrent pericarditis is the most common and troublesome complication
      of acute pericarditis affecting about one third of such patients. The pericardium
      may be involved in different systemic autoimmune diseases (i.e., systemic lupus
      erythematosus, rheumatoid arthritis, progressive systemic sclerosis, mixed
      connective tissue disease, Sjogren's Syndrome, polyarteritis, giant cell
      arteritis, other systemic vasculitides) either in a symptomatic form (usually
      during the active phase of the disease) or as asymptomatic pericardial effusion.
      Moreover, idiopathic recurrent pericarditis mimicks hereditary periodic fever
      syndromes (HPFSs). HPFSs are a group of disorders characterized by primary
      dysfunction of the innate immune system mostly caused by mutations of genes
      involved in the regulation or activation of the inflammatory response, without
      any apparent involvement of antigen-specific T cells or significant production of
      autoantibodies. These disorders usually manifest in the pediatric population,
      with onset ranging from the first hours to the first decade of life, however a
      limited number of patients experience disease onset during adulthood.

PMID- 21170608
TI  - Proof-editing is the bottleneck of 3D neuron reconstruction: the problem and
      solutions.

PMID- 21170607
TI  - Recent concepts of autoimmune pancreatitis and IgG4-related disease.
AB  - Recent studies suggested the existence of two subtypes of autoimmune pancreatitis
      (AIP): type 1 related with IgG4 (lymphoplasmacytic sclerosing pancreatitis; LPSP)
      and type 2 related with a granulocytic epithelial lesion (idiopathic duct-centric
      chronic pancreatitis; IDCP). Apart from type 2 AIP, the pathological features of
      type 1 AIP with increased serum IgG4/IgE levels, abundant infiltration of IgG4+
      plasmacytes and lymphocytes, fibrosis, and steroid responsiveness are suggestive
      of abnormal immunity such as allergy or autoimmunity. Moreover, the patients with
      type 1 AIP often have extrapancreatic lesions such as sclerosing cholangitis,
      sclerosing sialadenitis, or retroperitoneal fibrosis showing similar pathological
      features. Based on these findings, many synonyms have been proposed for these
      conditions, such as "multifocal idiopathic fibrosclerosis", "IgG4-related
      autoimmune disease", "IgG4-related sclerosing disease", "IgG4-related plasmacytic
      disease", and "IgG4-related multiorgan lymphoproliferative syndrome", all of
      which may refer to the same conditions. Therefore, the Japanese Research
      Committee for "Systemic IgG4-related Sclerosing Disease" proposed a disease
      concept and clinical diagnostic criteria based on the concept of multifocal
      fibrosclerosis in 2009, in which the term "IgG4-related disease" was appointed as
      a minimal consensus on these conditions. Although the significance of IgG4 in the
      development of "IgG4-related disease" remains unclear, we have proposed a
      hypothesis for the development of type 1 AIP, one of the IgG4-related disease.
      The concept and diagnostic criteria of "IgG4-related disease" will be changed in
      accordance with future studies.

PMID- 21170609
TI  - A new method for repeated "self-cloning" promoter replacement in Saccharomyces
      cerevisiae.
AB  - A method for repeated PCR-mediated promoter replacement in the yeast
      Saccharomyces cerevisiae is described. It was proposed to use the DNA fragment
      comprising the marker gene that enables both positive and negative selection (a
      selectable/counter-selectable marker) surrounded by direct repeats of the desired
      promoter as a promoter replacement cassette. This fragment is integrated upstream
      of the target gene because of PCR-added terminal sequences for homologous
      recombination with the target locus. Subsequent marker excision via homologous
      recombination between the copies of the two promoters leaves one copy of the
      desired promoter upstream of the target genes, without any heterologous scar
      sequence. To test this method, a set of plasmids bearing the S. cerevisiae URA3
      gene surrounded by two copies of the ADH1 or PGK1 promoter was constructed. Using
      these cassettes, the native promoters of the GSH1 and GSH2 genes were replaced in
      the ura3Delta0 recipient strains. The proposed method is useful for research
      applications due to simple marker excision, and for construction of "self
      cloning" industrial strains, because no heterologous DNA is retained in the
      genome of the resulting strain after marker excision.

PMID- 21170610
TI  - Hypocretin and its emerging role as a target for treatment of sleep disorders.
AB  - The neuropeptides hypocretin-1 and -2 (orexin A and B) are critical in the
      regulation of arousal and maintenance of wakefulness. Understanding the role of
      the hypocretin system in sleep/wake regulation has come from narcolepsy-cataplexy
      research. Deficiency of hypocretin results in loss of sleep/wake control with
      consequent unstable transitions from wakefulness into non-rapid eye movement
      (REM) and REM sleep, and clinical manifestations including daytime
      hypersomnolence, sleep attacks, and cataplexy. The hypocretin system regulates
      sleep/wake control through complex interactions between monoaminergic/cholinergic
      wake-promoting and GABAergic sleep-promoting neuronal systems. Research for the
      hypocretin agonist and the hypocretin antagonist for the treatment of sleep
      disorders has vigorously increased over the past 10 years. This review will focus
      on the origin, functions, and mechanisms in which the hypocretin system regulates
      sleep and wakefulness, and discuss its emerging role as a target for the
      treatment of sleep disorders.

PMID- 21170611
TI  - Diabetes and cardiovascular disease: the potential benefit of incretin-based
      therapies.
AB  - The health burden of type 2 diabetes mellitus continues to increase worldwide. A
      substantial portion of this burden is due to the development of cardiovascular
      disease in patients with diabetes. Recent failures of clinical trials of
      intensive glucose control to reduce macrovascular events, coupled with reports of
      potential harm of certain diabetic therapy, have led to increased scrutiny as new
      diabetic therapies are developed. Incretin peptides are a group of
      gastrointestinal proteins that regulate glucose metabolism through multiple
      mechanisms, and incretin-based therapies have been developed to treat type 2
      diabetes. These agents include glucagon-like peptide-1 (GLP-1) and dipeptidyl
      peptidase-IV (DPP-IV) inhibitors. In addition to effects on glucose homeostasis,
      growing evidence suggest that these peptides may also affect the cardiovascular
      system. In this review, we discuss recent findings concerning the potential, yet
      untested, benefits of incretin-based pharmacotherapy in the treatment of
      cardiovascular disease.

PMID- 21170612
TI  - Update on the role of endoscopic ultrasound in chronic pancreatitis.
AB  - Chronic pancreatitis (CP) remains an important healthcare problem that adversely
      affects quality of life. Endoscopic ultrasound (EUS) is a preferred test for the
      diagnosis of early CP. The Rosemont classification strictly defines and assigns
      weighting to the previously described ductal and parenchymal criteria. Recent
      histological correlation studies have improved our understanding of the accuracy
      of EUS criteria. Digital imaging analysis and complementary functional testing
      may complement endosonographic diagnosis. EUS-directed celiac plexus blockade and
      ductal access techniques have expanded the therapeutic armamentarium for pain
      management in CP.

PMID- 21170613
TI  - How should allergists deal with local reactions to allergen immunotherapy?
AB  - Despite the well-known benefits of subcutaneous immunotherapy (SCIT), adverse
      reactions include both local reactions (LRs) and systemic reactions. An LR is a
      well-known adverse event associated with SCIT injections and is defined as any
      swelling located at or near the injection site following allergen injection.
      Concerns that LRs might predict systemic reactions have historically motivated
      allergists to dose adjust for LRs. More recent data have dispelled this notion,
      although many allergists continue to dose adjust for other reasons. This article
      discusses the historical response to LRs and dose adjustments and reviews the
      most recent literature addressing LRs to SCIT. Treatment options, although they
      are either unproven or not studied, are offered as an alternative to routine dose
      adjustments for LRs. Education remains the foundation of physician-patient
      communication concerning LRs.

PMID- 21170614
TI  - The role of complement in the diagnosis and management of allergic rhinitis and
      allergic asthma.
AB  - Allergic rhinitis and asthma are common chronic inflammatory diseases of the
      nasal mucus membranes and the upper airways with a high prevalence in Western
      countries. In addition to maladaptive T-helper type 2 (Th2) immunity, Th17 cells
      can drive the inflammatory responses in both diseases. Several reports have shown
      that the complement system is activated locally and systemically in allergic
      rhinitis and/or allergic asthma patients. Importantly, recent findings in
      experimental models of allergic rhinitis and allergic asthma suggest that the
      complement cleavage products complement 3a and complement 5a and the activation
      of their corresponding receptors in antigen-presenting cells regulate the
      development of maladaptive Th2 and Th17 immunity. These findings in experimental
      asthma are corroborated by genome-wide searches and candidate gene studies in
      humans. We discuss recent findings in experimental and human allergic airway
      diseases suggesting that complement may serve as a new diagnostic and therapeutic
      target for both disorders.

PMID- 21170616
TI  - Iron and erythropoiesis: a dual relationship.
AB  - Iron is essential for cell life and especially for erythropoiesis which is the
      major body consumer of iron for red cell production. The study of genetic
      disorders of iron metabolism, the identification of iron transporters and of the
      role of hepcidin as the key regulator of systemic iron homeostasis have greatly
      contributed to our understanding of iron handling by the erythroid marrow.
      Spontaneous and engineered animal models of iron disorders have help to add
      further insights to the issue. A still incompletely understood aspect remains the
      regulation that erythropoiesis exerts on iron.

PMID- 21170618
TI  - Measuring surface roughness of pharmaceutical powders using vapor sorption
      methods.

PMID- 21170617
TI  - Stochastic acquisition of a stem cell-like state and drug tolerance in leukemia
      cells stressed by radiation.
AB  - A rare population of leukemia cells have the properties of leukemia stem cells
      (LSCs) and cause resistance to therapy, but their development is not clearly
      understood. In the current study, we show that a higher resistance to cytotoxic
      drug (Ara-C) can be developed in the subpopulation of promyelocytic leukemia
      cells that survived radiation treatment. These drug-tolerant leukemia cells
      (DTLs) are not observed immediately after radiation despite extensive genetic
      instability in the cells, but appear in 3 weeks of recovery culture. Moreover,
      when the single cell-derived clones were examined by clonal trafficking, no
      correlation between radio-resistant and chemo-resistant leukemic clones was
      detected, indicating that the resistance is developed by active acquisition of
      the resistance without clonal predisposition. Interestingly, the DTLs mimicked
      the characteristics of LSCs exhibiting leukemia-initiating activities and lower
      levels of reactive oxygen species or a higher level expression of bmi-1 as well
      as higher resistance to retinoic acid-induced differentiation compared to
      parental leukemic cells. These studies show that an active reacquisition of stem
      cell-like properties can occur in the leukemia cells to develop resistance to
      treatments and that such reacquisition process of leukemic cells occurs in a
      stochastic manner triggered by radiation stress on leukemic cells.

PMID- 21170619
TI  - Pitavastatin: a new 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor for
      the treatment of hyperlipidemia.
AB  - Statins have proven beneficial for reducing both primary and secondary events in
      patients with coronary heart disease. Tight control of serum lipid parameters in
      these patients is recommended by the most recent clinical guidelines. Although
      numerous lipid-lowering treatments are available, only a small percentage of
      eligible patients receive therapy and fewer achieve their lipid-lowering goals.
      Thus it is clear that new treatment strategies to manage patients with lipid
      abnormalities are warranted. Pitavastatin (Lival; Kowa Pharmaceuticals America,
      Montgomery, AL, USA) has been recently approved for the treatment of
      hypercholesterolemia and combined dyslipidemia. Pitavastatin 1-4 mg/day has shown
      similar low-density lipoprotein-reducing activity to other commercially available
      statins, including simvastatin and atorvastatin. Adverse events occurred at
      similar rates to other statins in clinical trials with favorable effects seen in
      patients with dyslipidemia and metabolic syndrome. Pharmacokinetic drug-drug
      interactions are minimized due to the lack of significant metabolism of
      pitavastatin by the cytochrome P450 enzyme system, although some drugs affect its
      uptake into hepatocytes and should be avoided. In addition to its higher
      acquisition cost, pitavastatin has not been shown to improve clinical outcomes in
      high-risk patient populations and thus may not be the agent of choice in many
      patients at this time in lieu of cheaper, clinically proven alternatives.

PMID- 21170620
TI  - Quality imaging guided through appropriate use: targeting our population for
      imaging.

PMID- 21170621
TI  - Nonsurgical management of spinal stenosis: how evidence-based are we?

PMID- 21170623
TI  - Sleep and general anesthesia.
AB  - PURPOSE: The mechanisms through which general anesthetics cause reversible loss
      of consciousness are characterized poorly. In this review, we examine the
      evidence that anesthetic-induced loss of consciousness may be caused by actions
      on the neuronal pathways that produce natural sleep. PRINCIPAL FINDINGS: It is
      clear that many general anesthetics produce effects in the brain (detected on
      electroencephalogram recordings) that are similar to those seen during non-rapid
      eye movement non-(REM) sleep. Gamma aminobutyric acid (GABA)ergic hypnogenic
      neurons are thought to be critical for generating non-REM sleep through their
      inhibitory projections to wake-active regions of the brain. The postsynaptic
      GABA(A) receptor is a major molecular target of many anesthetics and thus may be
      a point of convergence between natural sleep and anesthesia. Furthermore, we also
      present growing evidence in this review that modulating wake-active
      neurotransmitter (e.g., acetylcholine, histamine) release can impact on
      anesthesia, supporting the idea that this point of convergence is at the level of
      the brain arousal systems. CONCLUSIONS: While it is clear that general
      anesthetics can have effects at various points in the sleep-wake circuitry, it
      remains to be seen which points are true anesthetic targets. It will be
      challenging to separate non-specific effects on baseline arousal from a causal
      mechanism. Sophisticated experimental approaches are necessary to address basic
      mechanisms of sleep and anesthesia and should advance our understanding in both
      of these fields.

PMID- 21170622
TI  - Contribution of sedative-hypnotic agents to delirium via modulation of the sleep
      pathway.
AB  - PURPOSE: To review the mechanisms of sedative-hypnotic action with respect to the
      risk of delirium imparted by drugs that act on gamma-amino-butyric-acid type A
      receptors or alpha(2) adrenoceptors. SOURCE: MEDLINE was searched for relevant
      articles. PRINCIPAL FINDINGS: Development of the acute confusional state of
      delirium is associated with longer intensive care unit (ICU) and hospital lengths
      of stay, significantly higher risk of functional decline, and increased
      mortality. Disruption of sleep is a modifiable risk factor that may contribute to
      delirium and cognitive dysfunction in ICU patients. Among the functions of sleep
      are repair of defective processes and restoration of the brain to a state in
      which it is ready to acquire new knowledge. It is logical that disruption of
      these processes may produce acute confusion. Delirium develops through a complex
      interaction between the patient's baseline vulnerability (patient's predisposing
      risk factors before hospitalization) and precipitating factors or insults
      (modifiable events that occur during hospitalization). The latter factors include
      both sleep disruption and sedation. We present a hypothesis that these two
      factors are causally linked through effects on memory. Our hypothesis explains
      why patients randomized to receive an alpha(2) adrenoceptor agonist are less
      likely to develop delirium (and the attendant cognitive dysfunction) than those
      randomized to receive benzodiazepines. CONCLUSION: Herein we present our
      hypothesis that alternate mechanisms of hypnotic action may differentiate the
      deleriogenic properties of the two classes of sedatives. Future studies should
      focus on whether a causal relationship can be established between sedative
      administration, sleep disruption, and delirium.

PMID- 21170625
TI  - Risk factor analysis for acute type A aortic dissection after aortic valve
      replacement.
AB  - PURPOSE: Previous aortic valve replacement (AVR) is considered to be an
      independent risk factor for late acute type A aortic dissection (AAAD). However,
      the predictors of late AAAD at the time of AVR have not been characterized.
      METHODS: A total of 285 patients who underwent isolated AVR were followed for 7.6
      +/- 8.1 years (mean +/- SD). These 285 patients were divided into two groups.
      Group A consisted of 275 patients who did not develop late aortic complications
      after AVR, and group B consisted of 10 patients (3.5%) who developed late AAAD
      after AVR. RESULTS: The mean time interval between initial AVR and developing
      late AAAD was 6.1 +/- 5.2 years. The diameter of the ascending aorta at the time
      of AVR was significantly greater in group B than those of group A (47.7 +/- 4.6
      vs. 35.6 +/- 6.3 mm; P < 0.001). Univariate analysis identified other predictors
      as well: aortic regurgitation (P = 0.029), systemic hypertension (P < 0.001),
      thinning or fragility of the aortic wall (P < 0.001), and male sex (P = 0.039).
      CONCLUSION: Aortic regurgitation combined with systemic hypertension, male sex,
      and thinned or fragile aortic walls in patients with ascending aortic dilatation
      (>=45 mm diameter) at the time of AVR may be predisposing factors for
      postsurgical aortic complications. These patients should be considered for
      concomitant replacement of the ascending aorta unless the patient has a high
      operative risk or older age.

PMID- 21170624
TI  - How we recall (or don't): the hippocampal memory machine and anesthetic amnesia.
AB  - PURPOSE: The hippocampal formation occupies a central position for the processing
      of sensory input into learned, remembered, and consciously retrievable
      information. The mechanisms by which anesthetic drugs interfere with these
      processes are now emerging. We review the current understanding of the role of
      the hippocampal formation in the generation of memory traces and how anesthetics
      might interfere with its function. CLINICAL FEATURES: Intraoperative amnesia is a
      desired endpoint of general anesthesia from the perspective of both the patient
      and the practitioner. "Intraoperative awareness with recall" can result when
      learning and memory do occur. In addition, anesthetics are capable of inducing a
      state of "conscious amnesia" that can provide insight into the workings of the
      brain and might be useful clinically. CONCLUSIONS: Anesthesiologists routinely
      induce the most fascinating pharmacologic effects in existence, the reversible
      interference of anesthetics with higher cognitive functions. Understanding how
      the drugs in our custody exert their effects should be our contribution to
      mankind's universal knowledge base.

PMID- 21170626
TI  - Outcome after valve surgery in octogenarians and efficacy of early mobilization
      with early cardiac rehabilitation.
AB  - PURPOSE: This study aimed to compare postoperative complications and the surgical
      outcome in patients aged <80 years versus octogenarian patients. Another aim was
      to evaluate the safety and efficacy of early mobilization with early cardiac
      rehabilitation in octogenarians. METHODS: A retrospective analysis was performed
      in 138 consecutive patients (group Y comprised 118 patients <80 years, and group
      O comprised 20 octogenarians) who had undergone valve surgery at the authors'
      institution between July 2007 and December 2009. Furthermore, the efficacy of
      early mobilization with early cardiac rehabilitation and long-term results were
      analyzed in 40 consecutive octogenarian patients undergoing valve surgery from
      2000. The late survival follow-up was 100% complete. RESULTS: Redo cardiac
      operations were more frequent (O group 15.0% vs. Y group 3.4%, P = 0.011), and
      the preoperative EuroSCORE was significantly higher in group O than in group Y
      (group O 16.4 +/- 18.3 vs. group Y 7.5 +/- 9.1, P = 0.001). The incidence of
      delirium/confusion and worsening of renal function after surgery was higher in
      group O. The hospital mortality was 1.7% in group Y and no hospital death in
      group O (P > 0.99). Early mobilization with early cardiac rehabilitation
      significantly reduced the incidence of postoperative delirium/confusion and
      increased the number of patients who could return directly home. The actuarial 5
      year survival rate was 77.7% for octogenarians. CONCLUSION: Although there were
      more high-risk patients among the octogenarians, valve surgery was a safe, low
      risk procedure with excellent long-term results. Early mobilization with early
      cardiac rehabilitation was significantly effective and safe for postoperative
      recovery in octogenarians after cardiac valve surgery.

PMID- 21170627
TI  - Health-related quality of life evaluated by the eight-item short form after
      cardiovascular surgery.
AB  - PURPOSE: Owing to advances in cardiovascular surgery, patients with
      cardiovascular disease require improvement of health-related quality of life
      (QOL) than before. We measured the QOL of patients undergoing cardiovascular
      surgery using the eight-item Short Form (SF-8) and assessed its usefulness.
      METHODS: This was a prospective repeated-measures observational study. The SF-8
      questionnaire was completed through interviews with 117 consecutive adult
      patients undergoing cardiovascular surgery at a single center (Nagara Medical
      Center, Japan) from April 2006 to March 2008. The SF-8 was evaluated before
      surgery and at 7 days, 1 month, and 6 months after surgery. The physical and
      mental scores over time were assessed. RESULTS: Regarding physical status,
      compared with the normal population, the patients' scores were worse
      preoperatively and had deteriorated 7 days postoperatively; they gradually got
      closer to preoperative status a month after the procedure. At 6 months after
      surgery, all physical scores were higher than before surgery. The mental scores,
      including a mental component summary score, were inferior to those of the normal
      population until 1 month postoperatively, and they reached those of the normal
      population at 6 months. CONCLUSION: The SF-8 changed with the postoperative time
      course. It was a useful tool for analyzing the physical and mental QOL of
      patients who underwent cardiovascular surgery.

PMID- 21170628
TI  - Rapid expansion of another downstream aortic aneurysm with the elephant trunk.
AB  - A 75-year-old man developed persistent dysphagia 2 months after successful total
      arch replacement with a long elephant trunk (ET) for a distal arch aneurysm.
      Enhanced computed tomography revealed not only complete thrombosis of the distal
      arch aneurysm, but also rapid expansion of another downstream aortic aneurysm
      with esophageal compression. Thoracic endovascular aortic repair was undertaken
      for this symptomatic aortic aneurysm, which was totally thrombo-excluded. ET
      might produce turbulent or jet-like blood flow from its tip in some situations
      and have a potential to accelerate the expansion of the downstream aneurysm.
      Additional endovascular ET completion is simple, effective, and less invasive.

PMID- 21170629
TI  - Venous reconstruction with radial artery harvesting: Domino method.
AB  - We describe two cases of venous reconstruction after radial artery (RA)
      harvesting for coronary artery bypass grafting (CABG). Patient 1, a 70-year-old
      man who underwent CABG 16 years earlier, presented with acute posterolateral
      myocardial infarction caused by total occlusion of the saphenous vein graft
      (SVG). RA grafting was considered ideal, but he had bilateral hypoplastic ulnar
      arteries. Venous reconstruction with RA harvesting using SVG was performed, and
      surgery was successful. Patient 2, a 57-year-old-man with chronic renal failure
      caused by polycystic kidney disease, presented with angina pectoris. Off-pump
      CABG was recommended. We used a right internal thoracic artery and the RA as an I
      composite graft. However, RA preservation was essential for future hemodialysis.
      The RA was harvested and reconstructed as described for patient 1. Ischemia had
      not developed in the hands and forearms as of 5 years after the surgery. We
      believe that the method may be an alternative graft choice in CABG.

PMID- 21170631
TI  - Cerebral hemorrhage after mitral valve replacement in a patient with active
      infective endocarditis during the acute phase of a cerebellar infarction: a case
      report.
AB  - A 60-year-old woman presented with a high fever (39 degrees C or higher).
      Transthoracic echocardiography revealed a large and mobile vegetation on the
      anterior mitral leaflet with moderate mitral regurgitation. Computed tomography
      revealed a cerebellar infarction. The large vegetation had extended into the
      mitral annulus and had become mobile, and furthermore the patient failed with
      cardiac decompensation. Although the cerebellar infarction was still in the acute
      phase, we performed a radical resection of the vegetation and infected tissue,
      annular reconstruction with an autologous pericardial patch, and mitral valve
      replacement 3 days after admission. After the operation, the patient suffered
      from subsequent cerebral hemorrhage in the occipital lobe. The patient received
      medical treatment and was discharged successfully without sequelae.

PMID- 21170630
TI  - Infective endocarditis with cerebral mycotic aneurysm: treatment dilemma.
AB  - Cerebral mycotic aneurysms are uncommon but severe complications of infective
      endocarditis. Management of these patients remains controversial. We present a
      case of a 23-year-old man who had infective endocarditis complicated by an
      intracranial mycotic aneurysm. Because antimicrobial therapy was not effective in
      reducing the size of the mycotic aneurysm, a decision was made to perform
      craniotomy before cardiac surgery. The patient underwent an open heart operation
      20 days after aneurysm clipping. His postoperative course was uneventful, and the
      patient continues to be healthy without neurological complications.

PMID- 21170632
TI  - A papillary fibroelastoma of the aortic valve that presented with repeated chest
      pain.
AB  - A 70-year-old woman without any previous history of heart disease was referred to
      our hospital for repeated chest discomfort. She had experienced temporary
      hemiparesis because of a cerebral infarction of unknown etiology. Clinical
      evaluations were all within normal limits except for echocardiography. There was
      a mobile tumor in her ascending aorta, about 15 mm in diameter, adhering to a
      part of the right coronary cusp on its aortic side. Urgent surgery was performed.
      The tumor was attached to the edge of the right coronary cusp and excised with a
      part of the right coronary cusp, which was then repaired. Histological
      examination revealed the tumor to be a papillary fibroelastoma. The chest
      discomfort responsible for admission disappeared after the operation. In patients
      with events that may be embolic in nature and are not explained by other
      cardiovascular or neurological diseases, a cardiac source of emboli should be
      considered.

PMID- 21170633
TI  - Rudimentary right ventricle to pulmonary artery shunt in the Norwood procedure.
AB  - We describe here successful palliative repair of tricuspid atresia, hypoplastic
      right ventricle, transposition of the great arteries, and hypoplastic aortic arch
      in a neonate. The repair consisted of the Norwood procedure with a rudimentary
      right ventricle to pulmonary artery shunt, which was located on the right side of
      a neo-aorta. This procedure could be a useful adjunct to avoid left
      ventriculotomy and its subsequent dysfunction.

PMID- 21170634
TI  - Novel thoracoscopic approach to difficult posterior mediastinal tumors.
AB  - Thoracoscopic resection is the preferred treatment of posterior mediastinal
      tumors. However, thoracotomy may be necessary if the tumors are large or
      adherent; if they are demonstrate invasion or intraspinal growth; or if they are
      located in the superoposterior mediastinum or posterior costodiaphragmatic angle.
      We describe a case of a large, adherent posterior costodiaphragmatic mediastinal
      mass that would have been otherwise difficult to resect thoracoscopically if it
      were not for the three-dimensional visualization, greater dexterity, and accurate
      dissection offered by the Da Vinci robot.

PMID- 21170635
TI  - Endovascular stent-graft implantation for a cecum of an aberrant artery from a
      systemic arterial supply to the basal segment of the left pulmonary lobe.
AB  - A 64-year-old man with a history of repeated pneumonia underwent left lower
      lobectomy with a diagnosis of a systemic arterial supply to the basal segment of
      the left pulmonary lobe. Three months after the operation, follow-up computed
      tomography revealed a large cecum of the stump of the feeding artery. We
      performed endovascular aortic repair for the cecum.

PMID- 21170636
TI  - Thoracic empyema after laparoscopic cholecystectomy: an unusual cause.
AB  - Thoracic empyema after laparoscopic cholecystectomy is a rare complication. It is
      associated with dropped gallstones during the operation. In this case, we report
      a hepatocellular adenoma hemorrhage underneath an old diaphragm rupture, causing
      empyema after laparoscopic cholecystectomy.

PMID- 21170637
TI  - Localized extraosseous Ewing's sarcoma of the chest wall resected by video
      assisted thoracoscopic surgery.
AB  - Extraosseous Ewing's sarcoma (ES) is a small round cell tumor arising in soft
      tissue that was undifferentiated histologically from classic ES of bone. It
      frequently affects children and adolescents, with an unfavorable prognosis.
      Herein, we report a case of localized extraosseous ES of the chest wall resected
      by video-assisted thoracoscopic surgery (VATS). An asymptomatic 40-year-old man
      presented with an abnormal shadow on chest radiography. Chest computed tomography
      showed a 1.5-cm solid tumor on the chest wall. VATS was undertaken for the
      undiagnosed tumor. Thoracoscopic findings showed a hemispheric tumor with a
      smooth surface on the chest wall. The tumor was diagnosed with an extraosseous ES
      by pathological and cytogenetic examinations. As adjuvant therapy, the patient
      was treated with radiotherapy, followed by multiagent chemotherapy. There have
      been few reported cases in which VATS was used for extraosseous ES of chest wall,
      so our case was thought to be very rare.

PMID- 21170638
TI  - Radiation-induced osteosarcoma 17 years after mediastinal irradiation following
      surgical removal of thymoma.
AB  - Radiation-induced osteosarcoma is a rare complication after irradiation of
      primary malignancies. In the chest wall, it is usually secondary to radiotherapy
      for breast cancer or lymphoma. We report a rare case of radiation-induced
      osteosarcoma of the sternum after mediastinal irradiation of a thymoma. A 49-year
      old woman presented with a sternal tumor 17 years after surgery plus mediastinal
      irradiation (50 Gy) for a stage III thymoma. On biopsy, this second tumor was
      diagnosed as a radiation-induced osteosarcoma. Systemic survey revealed
      additional metastatic spread to vertebrae and pelvis. Despite intensive
      combination chemotherapy that initially stabilized her disease, the patient died
      2 years after the diagnosis was made. Because thymoma patients receiving
      mediastinal irradiation are thus at additional risk of radiation-induced
      secondary malignancy, long-term follow-up is advisable.

PMID- 21170639
TI  - Resection of giant mediastinal liposarcoma using the hemiclamshell incision.
AB  - A 39-year-old woman who had experienced slight chest discomfort for a few months
      was referred to our hospital with an abnormal shadow on a regular checkup chest X
      ray film. A computed tomography scan revealed a large well-defined mass in close
      relationship to the great vessels of the anterior mediastinum. Magnetic resonance
      imaging showed the anterior mediastinal mass, which was about 25 cm in diameter,
      expanding to the left pleural cavity with heterogeneous intensity. Because of the
      size and location of the mass, a combination of anterolateral thoracotomy and
      partial longitudinal median sternotomy--so-called hemiclamshell incision--was
      chosen, allowing excellent visualization and complete dissection of the giant
      tumor. The final histopathology of the resected specimen confirmed well
      differentiated liposarcoma.

PMID- 21170640
TI  - Perioperative antimicrobials in chest surgery patients positive for methicillin
      resistant Staphylococcus aureus.
AB  - In pulmonary surgery, methicillin-resistant Staphylococcus aureus (MRSA)-positive
      patients present an issue of perioperative antimicrobials. During 1996 to 2009 in
      a total of 1,080 pulmonary operations, MRSA was detected before 20 operations.
      Perioperatively, we followed the Sanford Guide using vancomycin (VCM) or
      arbekacin (ABK) in MRSA-positive cases at high risk (n = 14), including 1 with
      clinical infection and 13 with colonization. We used 1-day cefazolin (CEZ) in
      MRSApositive cases at low risk (n = 6). We defined the outcome as surgical site
      infection (SSI) that included death from infection. The 14 high-risk cases
      received a median of 3 days of VCM or ABK, of which 1 (7%) developed SSI. Of the
      cases given CEZ, we noted SSI in 1 of 6 low-risk cases (17%). Thus, MRSA-positive
      pulmonary surgery patients at large may receive 3-day VCM or ABK.

PMID- 21170641
TI  - Effects of calcium-fortified ice cream on markers of bone health.
AB  - Premenopausal women with low calcium intakes consumed calcium-fortified ice cream
      daily for 28 days. Bone markers, NTX, CTX and PTH decreased significantly by 7
      days, with some evidence of a calcium dose-dependent effect. Bone marker
      responses were observed within 1 h of consuming ice cream. Body weight remained
      constant over 28 days. INTRODUCTION: Dietary calcium is important for lifelong
      bone health. Milk is a good source of bioavailable calcium, but consumption has
      declined among young adults. The aims were to determine whether calcium-fortified
      ice cream, a palatable source of calcium, produces significant, sustainable
      changes in bone turnover markers and parathyroid hormone (PTH) in premenopausal
      women with calcium intake below recommended UK levels. METHODS: Eighty women,
      ages 20-39 years (calcium intake <750 mg/day) were randomised to consume lower
      saturated fat/sugar ice cream containing 96, 244, 459 or 676 mg calcium daily for
      28 days. Urinary NTX/Cr, serum CTX, PINP, 1,25D and PTH were measured (baseline,
      days 1, 7 and 28). Acute changes in CTX and PTH were measured over 5 h (n = 29
      women). RESULTS: There were significant mean decreases by 7 days in NTX/Cr, CTX,
      PTH and 1,25D and increases in PINP (one sample t tests), with a significant dose
      dependent effect on CTX analysis of covariance. Only CTX remained suppressed at
      28 days. Serum CTX and PTH decreased within 1 h. Body weight did not change
      significantly between baseline and 28 days. CONCLUSIONS: Daily consumption of
      calcium-fortified ice cream by premenopausal women may significantly reduce
      levels of the bone resorption marker serum CTX, without stimulating weight gain.
      The ice cream could be incorporated into the diet to replace low-calcium snacks
      and thus help individuals with habitually low calcium intakes to meet recommended
      intakes. The 244 mg calcium preparation would provide more than a quarter of the
      UK daily recommended nutrient intake for premenopausal women.

PMID- 21170642
TI  - Association between passive smoking in adulthood and phalangeal bone mineral
      density: results from the KRAM study--the Danish Health Examination Survey 2007
      2008.
AB  - The study investigates an association between phalangeal bone mineral density
      (BMD) and self-reported passive smoking using data on 15,038 persons (aged 18-95
      years), who underwent a BMD scan in the Danish KRAM study. BMD was significantly
      lower in persons exposed to long-term passive smoking in their home during
      adulthood. INTRODUCTION: Smoking is associated with decreased bone mineral
      density (BMD) and increased risk of osteoporotic fractures. This study aimed to
      investigate a possible association between BMD at the phalangeal bones and self
      reported passive smoking. METHODS: The study included a cohort of 15,544 men and
      women aged 18-95 years, who underwent a BMD scan in the Danish KRAM study. BMD
      scans of the middle phalanges of the second, third and fourth digits of the non
      dominant hand were performed with a compact radiographic absorptiometry system
      (Alara MetriScan(r)). Also, height, weight and body fat percentage were measured
      and 96.7% (n = 15,038) of the participants answered a self-reported questionnaire
      with information on passive smoking, other lifestyle factors, education, etc. The
      association between passive smoking and BMD was examined using multiple linear
      regression analysis. RESULTS: A total of 39.1% (n = 5,829) of the participants
      had been exposed to passive smoking in adulthood at home. BMD was significantly
      lower in subjects exposed to passive smoking, 0.343 vs. 0.331 g/cm(2); p < 0.01
      (unadjusted) and 0.339 vs. 0.337 g/cm(2); p < 0.05 (adjusted for age, gender,
      height and weight, and smoking). Multiple linear regression analysis showed that
      exposure to passive smoking for more than 20 years in adulthood at home was
      significantly related to BMD when adjusted for potential confounders (men, beta =
      -4.4 * 10(-3); r = -0.05; p < 0.01 and women, beta = -2.3 * 10 (-3); r = -0.03; p
      < 0.05). This relationship was also seen in the group of never smokers (beta = 
      3.3 * 10(-3); r = -0.03; p = 0.01). CONCLUSION: Our study supports a potential
      negative effect of long-term passive smoking in adulthood at home on phalangeal
      BMD.

PMID- 21170643
TI  - Fracture risk and adjuvant hormonal therapy among a population-based cohort of
      older female breast cancer patients.
AB  - The risk of hip and other fractures was examined among a population-based group
      of older women with breast cancer. Women using aromatase inhibitors (AIs) were
      found to be over three times more likely to have a hip fracture over
      approximately 3 years' follow-up. Other fracture risk factors were also
      identified. INTRODUCTION: Aromatase inhibitors have been shown in randomized
      trials to increase total fracture risk compared with tamoxifen, but the fracture
      risks in the trials were relatively low, and no difference in hip fracture has
      been demonstrated. METHODS: A population-based cohort of 2003 breast cancer
      survivors >=65 were followed prospectively for a median of 36 months. Patient
      survey information regarding adjuvant breast cancer therapies, prescription
      osteoporosis treatments, and other factors potentially associated with fracture
      was supplemented with cancer registry information. Hip and total nonvertebral
      fractures were determined using a validated Medicare algorithm, and the
      association of these fractures with adjuvant hormonal therapies was examined
      using Cox models. RESULTS: The cohort of 2,748 women with a mean age of 72.8 (SD
      5.4) included 28.2% who took an aromatase inhibitor and 27.8% tamoxifen. There
      were 41 hip fractures (1.5%) and 218 nonvertebral fractures (7.9%) among the
      cohort. Subjects using AIs (adjusted hazard ratio 3.24 (1.05, 9.98)) and subjects
      not using hormone therapy (3.32 (1.14, 9.65)) were more likely than users of
      tamoxifen to have a hip fracture. Bisphosphonate use was more common among AI
      users but did not explain these results. Users of AIs were more likely to have
      nonvertebral fractures, but this result did not reach statistical significance
      (adjusted hazard 1.34 (0.92, 1.94)). CONCLUSIONS: Hip and other fractures were
      common in an older population-based cohort of breast cancer survivors, and
      aromatase inhibitor use was associated with an increase in the short-term risk of
      hip fractures not detected in randomized controlled trials.

PMID- 21170644
TI  - Gene duplication and divergence of long wavelength-sensitive opsin genes in the
      guppy, Poecilia reticulata.
AB  - Female preference for male orange coloration in the genus Poecilia suggests a
      role for duplicated long wavelength-sensitive (LWS) opsin genes in facilitating
      behaviors related to mate choice in these species. Previous work has shown that
      LWS gene duplication in this genus has resulted in expansion of long wavelength
      visual capacity as determined by microspectrophotometry (MSP). However, the
      relationship between LWS genomic repertoires and expression of LWS retinal cone
      classes within a given species is unclear. Our previous study in the related
      species, Xiphophorus helleri, was the first characterization of the complete LWS
      opsin genomic repertoire in conjunction with MSP expression data in the family
      Poeciliidae, and revealed the presence of four LWS loci and two distinct LWS cone
      classes. In this study we characterized the genomic organization of LWS opsin
      genes by BAC clone sequencing, and described the full range of cone cell types in
      the retina of the colorful Cumana guppy, Poecilia reticulata. In contrast to X.
      helleri, MSP data from the Cumana guppy revealed three LWS cone classes.
      Comparisons of LWS genomic organization described here for Cumana to that of X.
      helleri indicate that gene divergence and not duplication was responsible for the
      evolution of a novel LWS haplotype in the Cumana guppy. This lineage-specific
      divergence is likely responsible for a third additional retinal cone class not
      present in X. helleri, and may have facilitated the strong sexual selection
      driven by female preference for orange color patterns associated with the genus
      Poecilia.

PMID- 21170645
TI  - Molecular evolution and characterization of fungal indoleamine 2,3-dioxygenases.
AB  - Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are
      tryptophan-degrading enzymes. Mammalian IDO expression is induced by cytokines
      and has antimicrobial and immunomodulatory effects. A major role of mammalian TDO
      is to supply nicotinamide adenine dinucleotide (NAD(+)). In fungi, the IDO
      homologue is thought to be expressed constitutively and supply NAD(+), as TDO is
      absent from their genomes. Here, we reveal the distribution of IDO genes among
      fungal species and characterize their enzymatic activity. The yeast,
      Saccharomyces cerevisiae has only one IDO gene, whereas the koji-mold,
      Aspergillus oryzae has two genes, IDOalpha and IDObeta. The A. oryzae IDOalpha
      showed more similar enzymatic properties to those of S. cerevisiae IDO than
      IDObeta, suggesting that the A. oryzae IDOalpha is a functional homologue of the
      S. cerevisiae IDO. From the IDObeta gene, two isoforms, IDObeta and IDObeta(+)
      could be generated by alternative splicing. The latter contained a 17 amino acids
      insertion which were encoded by the first intron of IDObeta gene. In comparison
      to IDObeta(+), bacterially expressed IDObeta showed much lower K(m) value and
      more than five-times faster V(max) value, resulting in 85 times higher catalytic
      efficiency; i.e., the removal of the domain encoded by the first intron from
      IDObeta(+) increases its enzymatic activity drastically. This might be a unique
      regulation mechanism of the L-Trp metabolism in the A. oryzae. The levo-1-methyl
      tryptophan (L-1MT) is a good inhibitor of both IDO1 and IDO2. However, the
      activity of fungal IDOs tested was not inhibited at all by L-1MT.

PMID- 21170646
TI  - Ipilimumab experience in heavily pretreated patients with melanoma in an expanded
      access program at the University Hospital of Siena (Italy).
AB  - AIM OF STUDY: To evaluate the feasibility of ipilimumab treatment for metastatic
      melanoma outside the boundaries of clinical trials, in a setting similar to that
      of daily practice. METHODS: Ipilimumab was available upon physician request in
      the Expanded Access Programme for patients with life-threatening, unresectable
      stage III/IV melanoma who failed or did not tolerate previous treatments and for
      whom no therapeutic option was available. Induction treatment with ipilimumab 10
      mg/kg was administered intravenously every 3 weeks, for a total of 4 doses, with
      maintenance doses every 12 weeks based on physicians' discretion and clinical
      judgment. Tumors were assessed at baseline, Week 12, and every 12 weeks
      thereafter per mWHO response criteria, and clinical response was scored as
      complete response (CR), partial response (PR), stable disease (SD), or
      progressive disease. Durable disease control (DC) was defined as SD at least 24
      weeks from the first dose, CR, or PR. RESULTS: Disease control rate at 24 and 60
      weeks was 29.6% and 15%, respectively. Median overall survival at a median follow
      up of 8.5 months was 9 months. The 1- and 2-year survival rates were 34.8% and
      23.5%, respectively. Changes in lymphocyte count slope and absolute number during
      ipilimumab treatment appear to correlate with clinical response and survival,
      respectively. Adverse events were predominantly immune related, manageable, and
      generally reversible. One patient died from pancytopenia, considered possibly
      treatment related. CONCLUSION: Ipilimumab was a feasible treatment for malignant
      melanoma in heavily pretreated, progressing patients. A sizeable proportion of
      patients experienced durable DC, including benefits to long-term survival.

PMID- 21170647
TI  - Gc protein-derived macrophage-activating factor (GcMAF) stimulates cAMP formation
      in human mononuclear cells and inhibits angiogenesis in chick embryo
      chorionallantoic membrane assay.
AB  - The effects of Gc protein-derived macrophage-activating factor (GcMAF) have been
      studied in cancer and other conditions where angiogenesis is deregulated. In this
      study, we demonstrate for the first time that the mitogenic response of human
      peripheral blood mononuclear cells (PBMCs) to GcMAF was associated with 3'-5'
      cyclic adenosine monophosphate (cAMP) formation. The effect was dose dependent,
      and maximal stimulation was achieved using 0.1 ng/ml. Heparin inhibited the
      stimulatory effect of GcMAF on PBMCs. In addition, we demonstrate that GcMAF (1
      ng/ml) inhibited prostaglandin E(1)- and human breast cancer cell-stimulated
      angiogenesis in chick embryo chorionallantoic membrane (CAM) assay. Finally, we
      tested different GcMAF preparations on CAM, and the assay proved to be a
      reliable, reproducible and inexpensive method to determine the relative potencies
      of different preparations and their stability; we observed that storage at room
      temperature for 15 days decreased GcMAF potency by about 50%. These data could
      prove useful for upcoming clinical trials on GcMAF.

PMID- 21170648
TI  - Potential candidate biomarkers for heterogeneity in triple-negative breast cancer
      (TNBC).
AB  - PURPOSE: Triple-negative breast cancer (TNBC) exhibits a distinct pattern of
      recurrence characterized by a rapidly rising rate in the first 2 years with a
      peak at 2-3 years, followed by a decline over the next 5 years. However, some
      TNBC patients exhibit indolent clinical behavior. The aim of this study was to
      investigate clinical characteristics and outcomes of metastatic TNBCs. In
      addition, we were to find out the marker which could divide TNBCs into a few
      subgroups according to different clinical features. METHODS: We retrospectively
      analyzed the clinicopathologic characteristics and outcomes of patients with
      metastatic TNBC who received palliative treatment between 1999 and 2007. RESULTS:
      The median relapse-free survival (RFS) and overall survival (OS) of 152 patients
      were 24 and 20 months, respectively. Divided TNBCs based on a RFS of 36 months,
      the patients with a RFS of >=36 months had a better disease control rate (DCR),
      progression-free survival (PFS), and OS than those with a RFS of <3 years. Cox
      regression multivariate analysis for RFS and OS revealed EGFR positivity and a
      low BRCA1 score as an independent risk factor for OS. CONCLUSIONS: The patients
      with a RFS >= 3 years had a significantly better DCR, PFS, and OS than patients
      who had a RFS < 3 years. BRCA1 and EGFR expression may be candidate determinants
      to distinguish RFS. A prospective clinical trial for different therapeutic
      strategies is needed for each subgroup.

PMID- 21170649
TI  - Thymidylate synthase and thymidine phosphorylase as predictive markers of
      capecitabine monotherapy in patients with anthracycline- and taxane-pretreated
      metastatic breast cancer.
AB  - PURPOSE: The primary purpose of this study was to evaluate the role of
      thymidylate synthase (TS) and thymidine phosphorylase (TP) as biomarkers to
      predict clinical outcomes of capecitabine monotherapy in patients with
      anthracycline- and taxane-pretreated metastatic breast cancer (MBC). METHODS: Of
      the patients who were previously treated with anthracycline and taxane regimens,
      90 patients who had available tissue block for immunohistochemistry with
      measurable lesions were included. All patients received capecitabine (2,500
      mg/m(2)/day) for 14 days every 3 weeks. RESULTS: High TS expression was more
      common among patients with triple-negative (TN) subtype than among patients with
      other subtypes (33% for hormone receptor+, 8% for HER2+, and 58% for TN, P =
      0.023). The median PFS was significantly lower in patients with high TS (6.6 vs.
      3.0 months; P = 0.017) and low TP expressions (6.0 vs. 3.3 months; P = 0.013). A
      high TS and a low TP expressions were identified as unfavorable independent risk
      factors for PFS to capecitabine monotherapy in multivariate analysis (hazard
      ratio [HR], 1.7, P = 0.037 for high TS score; HR, 1.8, P = 0.014 for low TP
      score). CONCLUSIONS: Our data suggest that high TS and low TP scores correlate
      with a shorter PFS for capecitabine monotherapy in patients with anthracycline-
      and taxane-pretreated MBC.

PMID- 21170650
TI  - Circulating endothelial cells predict for response to bevacizumab-based
      chemotherapy in metastatic colorectal cancer.
AB  - PURPOSE: Standardized enumeration of CEC counts is required to minimize
      variability and allow cross-studies comparisons. The purpose of this paper is to
      identify CEC threshold proposal, by CellSearch system, for determining response
      to bevacizumab-based chemotherapy in metastatic colorectal cancer. METHODS: From
      July 2007 to June 2008, 33 patients treated with FOLFOX4 plus bevacizumab were
      enrolled in a prospective study. From January 2007 to June 2007, before
      bevacizumab was approved by the government in Japan, 31 patients treated with
      FOLFOX4 as a control were enrolled. CECs of whole blood at the baseline, day 4, 2
      weeks after initiation of chemotherapy were isolated and counted using CellSearch
      system. RESULTS: There was no correlation between CEC levels and the outcome in
      the FOLFOX4. In the bevacizumab-based chemotherapy, CEC levels at the baseline
      were significantly associated with the outcome. Patients with 65 or more CECs at
      the baseline had a shorter median PFS and OS, than the median PFS and OS of less
      than 65 CECs at the baseline in the bevacizumab-based chemotherapy (P = 0.003, P
      = 0.027, respectively). By univariate and multivariate Cox proportional-hazards
      regression, CEC levels (cut-off; 65) at the baseline indicated the strongest
      predictor for the outcome to bevacizumab-based chemotherapy. CONCLUSION: A
      threshold of lower than 65 CECs, by the CellSearch System, at the baseline was a
      significant predictor of the outcome for colorectal cancer patients treated with
      bevacizumab-based chemotherapy.

PMID- 21170651
TI  - [Three-dimensional visualization of sclerotomies with ultrasound biomicroscopy.
      Comparison of 20 and 23 gauge incisions on the porcine eyeball].
AB  - BACKGROUND: When pars plana vitrectomy is performed, the sizes of the sclerotomy
      cannula vary between 20 and 23 gauge. We examined the morphology of the scleral
      tunnels by ultrasound biomicroscopy additionally taking into account the incision
      angle. MATERIAL AND METHODS: In each of 16 enucleated porcine eyes three 20 or 23
      gauge sclerotomies with varying angles between 30 and 90 degrees  to the
      horizontal level were performed. The vertical 20 gauge sclerotomies were
      additionally sealed by 7.0 vicryl cross-stitching. The resulting scleral channels
      were analysed by 3-D ultrasound biomicroscopy. RESULTS: The sclerotomies were
      echographically detectable in all cases. Analysis revealed that the sutured
      straight 20 gauge tunnels were hyporeflective in only some parts while the other
      incisions showed continuous hyporeflectivity along the complete channel in many
      cases. The smaller the instruments used and the flatter the scleral angles
      chosen, the smaller were the measured widths of the incision tunnels. CONCLUSION:
      Imaging sclerotomies ex vivo by ultrasound biomicroscopy is reliably
      reproducible. In the echographic pictures straight 20 gauge incisions appeared to
      be safely sealed by the sutures while the nonsealed tunnels often showed
      continuous patency. By choosing small instruments and flat incision angles the
      width of the resulting scleral channels can be reduced.

PMID- 21170652
TI  - [Early treatment of exudative age-related macular degeneration with ranibizumab
      (Lucentis(r)): the key to success].
AB  - BACKGROUND: Intravitreal ranibizumab (Lucentis(r)) is an effective treatment for
      exudative age-related macular degeneration (AMD). Up to now, settlement for this
      therapy remains quite complex and is handled differently by insurance companies
      as well as in the different German states. Often applications must be submitted
      and approved before an injection can be made. This procedure is time consuming
      and a delay in starting treatment might result. The aim of this study was to
      determine the effect of late-onset injection on visual acuity before and during
      the upload procedure. METHODS: All patients treated with ranibizumab
      intravitreally between February 2007 and May 2010 were retrospectively evaluated
      for their best-corrected visual acuity at the day of diagnosis, injections during
      the upload phase and first follow-up visit after upload. RESULTS: A total of
      1,149 eyes were evaluated and divided into 2 groups according to time between
      diagnosis and first injection (group 1: <=10 days, group 2: >10 days). There was
      no statistically significant difference between the groups for average age,
      gender, visual acuity at day of diagnosis and type of choroidal
      neovascularisation. However, both groups differed in the loss of visual acuity
      before the first injection and the possible increase in visual acuity. Group 1
      waiting <=10 days showed - in contrast to group 2 waiting >10 days--a smaller
      loss of visual acuity before upload and greater gain of visual acuity during
      upload. Those differences were statistically significant. CONCLUSION: Successful
      treatment of exudative AMD requires small intervals between diagnosis and first
      ranibizumab injection. After diagnosis, the first injection with ranibizumab
      should be given as early as possible.

PMID- 21170654
TI  - [A rare cause of syncope in a patient treated with the TASH procedure].
AB  - In patients with hypertrophic cardiomyopathy (HOCM), the decision for an
      implantable cardioverter-defibrillator (ICD) depends highly on the exact
      identification of the etiology of syncope. In this article, the case of a patient
      with HOCM and syncope is reported. Invasive pressure measurement was used to
      diagnose a typical case of cough syncope as the cause of the syncope.

PMID- 21170653
TI  - [Postkeratoplasty astigmatism: comparison of three suturing techniques].
AB  - PURPOSE: The aim of this study was a retrospective analysis of postkeratoplasty
      astigmatism and best corrected visual acuity (BCVA) in patients following
      penetrating keratoplasty (PK) and a comparison of three suturing techniques.
      PATIENTS AND METHODS: In this retrospective analysis penetrating keratoplasty
      (PK) was carried out on 150 eyes with 3 suturing techniques: single running (SR),
      double running (DR counterclockwise) and interrupted (IR) sutures. Of the eyes 37
      (24.7%) underwent PK with SR sutures, 81 eyes (54%) with DR sutures and 32 eyes
      (21.3%) had IR. PK for Fuchs' dystrophy was used on 46 eyes (30.7%), on 33 eyes
      (22%) for keratoconus, on 12 eyes (8%) for herpetic keratitis and on 7 eyes
      (4.6%) for pseudophakic bullous keratopathy. For trephination a guided trephine
      system (GTS) was used in 44%, rotortrepan in 46.6% and best trepan in 5.3%.
      Postkeratoplasty astigmatism and best corrected visual acuity (BCVA) were
      evaluated 1, 4, 12 and 24 months after surgery (all sutures removed). Subjective
      and objective refractions and corneal topography were performed to assess
      astigmatism. The Kolmogorov-Smirnov test (95% significance) was used to evaluate
      statistical significance. RESULTS: Mean topographic astigmatism 4 months (12
      months/2 years) after keratoplasty was 4.9 dpt (5.3/4.1, n=4) for SR, 4.2 dpt
      (4.0/5.3) for DR and 9.7 dpt (n=7) (4.9, n=8/6.8, n=2) for IR suturing
      techniques. Mean objective astigmatism 4 months (12 months/2 years) after PK was
      5.9 dpt (4.1, n=7/5.0, n=3) for SR, 3.4 dpt (4.5/4.98) for DR and 8.0 dpt (n=3)
      (6.9, n=4/7.4, n=2) for IR sutures. Mean refractive cylinder 4 months (12
      months/2 years) after keratoplasty was 4.5 dpt (3.9/4.9) for SR, 3.2 dpt
      (3.3/3.6) for DR and 6.2 dpt (3.7/4.7) for IR suturing. Mean BCVA 4 months (12
      months/2 years) was 0.3 (0.3/0.4) for SR, 0.3 (0.4/0.5) for DR and 0.3 (0.4/0.4)
      for IR sutures. BCVA 4 months (12 months/2 years) after PK (GTS only) reached 0.3
      (0.3/0.5) for SR and 0.3 (0.4/0.6) for DR suturing. DISCUSSION: Topographic and
      objective astigmatisms were highest for the IR suturing technique. Topographic
      astigmatism and refractive cylinder were less in the DR (compared to SR) group 4
      and 12 months after surgery (statistically significant). After suture removal (2
      years after PK) refractive cylinder was still lower for DR compared to SR but
      there was no statistical difference between DR and SR regarding topographic and
      objective cylinders. For the interpretation of these data it should be emphasized
      that due to the retrospective character of this analysis the number of patients
      in the subgroups is decreasing with time and as a consequence single (strongly
      deviating) measurements can have a more powerful impact on the outcome in the
      individual subgroups.

PMID- 21170655
TI  - Differentiating cerebellar and brainstem lesions with ocular vestibular-evoked
      myogenic potential test.
AB  - This study applied both ocular vestibular-evoked myogenic potential (oVEMP) and
      cervical VEMP (cVEMP) tests in patients with cerebellar disorders to determine
      whether VEMP test can differentiate between cerebellar and brainstem lesions. A
      total of 12 patients with cerebellar disorder, including extended cerebellar
      lesion (involving the brainstem) in 8 and localized cerebellar lesion (excluding
      the brainstem) in 4, were enrolled in this study. All patients underwent caloric,
      visual suppression, and oVEMP and cVEMP tests via bone-conducted vibration
      stimuli. The abnormal rates for the caloric, visual suppression, and oVEMP and
      cVEMP tests were 62, 83, 88 and 75% in patients with extended cerebellar lesion
      and 0, 25, 0 and 0% in those with localized cerebellar lesion, respectively. The
      rate of abnormal oVEMP results significantly differed between the two groups, but
      caloric, visual suppression and cVEMP test results did not differ. In another ten
      healthy subjects, characteristic parameters of oVEMPs obtained under light and
      dark conditions did not significantly differ. In conclusion, ocular VEMP test can
      differentiate between cerebellar and brainstem lesions. Abnormal oVEMPs in
      patients with cerebellar disorder may indicate adjacent brainstem involvement.

PMID- 21170656
TI  - Increased c-Jun N-terminal kinase activation in human endometriotic endothelial
      cells.
AB  - Endometriosis is a common inflammatory gynecological disease characterized by the
      presence of endometrial tissue outside of the uterine cavity. The c-Jun N
      terminal kinase (JNK) is a subfamily of the mitogen-activated protein kinases
      (MAPKs) involved in cellular processes ranging from cytokine expression to
      apoptosis, and is activated in response to inflammation and cellular stress. We
      hypothesized that inflammatory cytokines in the peritoneal microenvironment
      increase JNK MAPK activity in endometriotic endothelial cells, and that human
      endometrial endothelial cells (HEECs) may be involved in inflammatory
      pathogenesis of endometriosis. Thus, we evaluated the expression of the total-
      and phosphorylated-(phospho)-JNK in endometrial and endometriotic endothelial
      cells in vivo, and in HEECs treated with normal peritoneal fluid (NPF),
      endometriotic peritoneal fluid (EPF), and the inflammatory cytokines interleukin
      1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) in vitro. Phospho
      JNK immunoreactivity in HEECs in normal endometrium was significantly higher in
      the early proliferative and late secretory phases compared to other phases. Both
      eutopic and ectopic HEECs from the early secretory phase also revealed higher
      phospho-JNK immunoreactivity, compared to their respective cycle-matched normal
      HEECs. Moreover, HEECs treated with EPF showed significantly higher phospho-JNK
      levels compared to that in HEECs treated with NPF. In conclusion, our in vivo and
      in vitro findings suggest that increased phosphorylation of JNK in HEECs from
      women with endometriosis is likely due to high level of IL-1beta and TNF-alpha in
      peritoneal fluid; this in turn may up-regulate inflammatory cytokine expression
      and thus play a role in the pathogenesis of endometriosis.

PMID- 21170657
TI  - A fluorescence-based polymerase chain reaction-linked single-strand conformation
      polymorphism (F-PCR-SSCP) assay for the identification of Fasciola spp.
AB  - The present study aimed to establish a fluorescence-based polymerase chain
      reaction-linked single-strand conformation polymorphism (F-PCR-SSCP) assay for
      the identification of Fasciola spp. Based on the sequences of the second internal
      transcribed spacer (ITS-2) of the nuclear ribosomal DNA, we designed a set of
      genus-specific primers for the amplification of Fasciola ITS-2, with an estimated
      size of 140 bp. These primers were labelled by fluorescence dyes, and the PCR
      products were analyzed by capillary electrophoresis under non-denaturing
      conditions (F-PCR-SSCP). Capillary electrophoresis analysis of the fluorescence
      labelled DNA fragments displayed three different peak profiles that allowed the
      accurate identification of Fasciola species: one single peak specific for either
      Fasciola hepatica or Fasciola gigantica and a doublet peak corresponding to the
      "intermediate" Fasciola. Validation of our novel method was performed using
      Fasciola specimens from different host animals from China, Spain, Nigeria, and
      Egypt. This F-PCR-SSCP assay provides a rapid, simple, and robust tool for the
      identification and differentiation between Fasciola spp.

PMID- 21170658
TI  - Laparoendoscopic single-site retroperitoneoscopic adrenalectomy: a matched-pair
      comparison with the gold standard.
AB  - BACKGROUND: Laparoscopic adrenalectomy has become the gold-standard for the
      surgical treatment of most adrenal lesions. This study evaluated the operative
      outcome of laparoendoscopic single-site (LESS) retroperitoneoscopic adrenalectomy
      (LESS-ARA) in comparison with the current standard operation procedure. METHODS:
      Between June and December 2009, 19 patients underwent LESS-ARA, and their
      outcomes were compared with a contemporary 1:2 matched-pair cohort of 38 patients
      who underwent standard ARA by the same surgeon. In LESS-ARA, a multichannel port
      was inserted through a 2.5- to 3.0-cm transverse skin incision below the tip of
      the 12th rib. The LESS-ARA procedure was performed using a 5-mm 30o laparoscopic
      camera and two standard laparoscopic instruments. The following parameters were
      compared between the two groups: demographics, details of the surgery,
      perioperative complications, postoperative visual analog pain scale score,
      analgesic requirement, and short-term measures of convalescence. RESULTS: The
      finding showed that LESS-ARA and standard ARA were comparable in terms of the
      estimated blood loss (30 vs 17.5 ml; p=0.64), postoperative hospital stay (6 vs 6
      days; p=0.67), and postoperative complications (2 vs 3 patients; p=1.00) for
      patients with similar baseline demographics and median tumor size (2.1 vs 3.0;
      p=0.18) cm. The intraoperative hemodynamic values were similar in the two groups.
      The LESS-ARA group had a longer median operative time (55 vs 41.5 min; p=0.0004),
      whereas the in-hospital use of analgesics was significantly less (5 vs 12
      morphine equivalents; p=0.03). CONCLUSIONS: The LESS retroperitoneoscopic
      adrenalectomy approach is feasible and offers a superior cosmetic outcome and
      better pain control, with perioperative outcomes and short-term measures of
      convalescence similar to those of the standard approach, albeit with a longer
      operative time.

PMID- 21170659
TI  - Emergency preoperative stenting versus surgery for acute left-sided malignant
      colonic obstruction: a multicenter randomized controlled trial.
AB  - BACKGROUND: Surgical management of left colonic cancer presenting as an acute
      obstruction remains controversial and still is associated with high mortality and
      morbidity rates. Recently, self-expandable metallic stents (SEMS) have been used
      as a bridge to surgery in an attempt to decompress the colon and then allow
      elective one-stage surgical resection without stoma placement. This study aimed
      to compare the outcomes of emergency surgery alone with emergency placement of
      colonic SEMS as a bridge to surgery in terms of efficiency and reduction of the
      stoma placement rate. METHODS: A multicenter prospective, randomized, controlled
      trial was conducted according to the consolidated standards of reporting trials
      (CONSORT) Statement criteria. Patients eligible for the study were randomized to
      either emergency surgery or emergency SEMS as a bridge to surgery. The primary
      outcome was the need for a stoma (temporary or permanent) for any reason. The
      secondary end points were mortality, morbidity, and length of hospital stay.
      RESULTS: Nine centers participated in the trial. Among the 70 patients eligible
      for the study, 60 were randomized and included for the final analysis, 30
      patients in each group. Seven patients were randomized but did not fulfill the
      entry requirements, whereas three further eligible patients were not randomized
      for various reasons. Concerning the primary outcome, 17 patients in the surgery
      group sustained a stoma placement versus 13 patients in the SEMS group (p=0.30).
      No statistically significant difference was noted concerning the secondary
      outcomes. A total of 16 attempts at SEMS placement (53.3%) were technical
      failures. Two colonic perforations directly related to the stent placement
      procedure occurred among the 30 randomized patients and 1 perforation occurred
      among the nonrandomized patients, leading to premature closure of inclusions in
      the study before the expected number of 80 patients was reached. CONCLUSION: This
      randomized trial failed to demonstrate that emergency preoperative SEMS for
      patients presenting with acute left-sided malignant colonic obstruction could
      significantly decrease the need for stoma placement.

PMID- 21170660
TI  - Malignant biliary stenosis: conventional cytology versus DNA image cytometry.
AB  - BACKGROUND: The aim of this study is to evaluate the utility of image cytometry
      (ICM)-DNA analysis on cytological brush specimens in improving the sensitivity
      and diagnostic accuracy for biliary neoplasias. METHODS: A total of 71 patients
      with 89 samples of biliary tree brushing from a stenosis were included in this
      prospective study. Conventional cytology (CC) and DNA ploidy using ICM of the
      brushing were performed. Benign or malignant findings were confirmed by surgical
      exploration or a clinical follow-up of at least 12 months. RESULTS: Diagnosis was
      confirmed by clinical follow-up in 44 cases and surgical investigation or
      histology in 41 cases. A definitive diagnosis of the smears resulted in 40
      malignant and 49 benign diagnoses. The sensitivity was 0.666 for CC and 0.658 for
      ICM, and the specificity was 0.920 and 0.937, respectively. The positive
      predictive value (PPV) was 0.866 for CC and 0.900 for ICM. McNemar's test did not
      reveal a significant difference between CC and ICM (P=0.803). Agreement of the
      two methods was found in 73 samples, raising specificity to 0.998 but not
      sensitivity (0.725). CONCLUSIONS: ICM-DNA seems not to improve significantly the
      PPV and NPV for detecting neoplasias of the biliary tract compared to CC.
      Nevertheless a clinical advantage can be seen in the agreement of the two methods
      in diagnosing dysplasia or cancer, since it did not show false positive results.

PMID- 21170661
TI  - Mammary ductoscopy in the current management of breast disease.
AB  - BACKGROUND: The majority of benign and malignant lesions of the breast are
      thought to arise from the epithelium of the terminal duct-lobular unit (TDLU).
      Although modern mammography, ultrasound, and MRI have improved diagnosis, a final
      pathological diagnosis currently relies on percutaneous methods of sampling
      breast lesions. The advantage of mammary ductoscopy (MD) is that it is possible
      to gain direct access to the ductal system via the nipple. Direct visualization
      of the duct epithelium allows the operator to precisely locate intraductal
      lesions, enabling accurate tissue sampling and providing guidance to the surgeon
      during excision. The intraductal approach may also have a role in screening
      individuals who are at high risk of breast cancer. Finally, in spontaneous nipple
      discharge (SND), as biopsy instruments improve and intraductal therapeutics, such
      as intraductal excision and laser ablation, become a possibility, normal or
      benign ductoscopic findings may help minimize surgery in selected patients. As MD
      technology is rapidly advancing, a comprehensive review of current practice will
      be a valuable guide for clinicians involved in the management of breast disease.
      METHODS: This is a review of current ductoscopic practice based on an exhaustive
      literature search of Pubmed, Google Scholar, and conference proceedings. The
      search terms "ductoscopy", "duct endoscopy", "mammary", "breast," and
      "intraductal" were used. RESULTS/CONCLUSIONS: Duct endoscopes have become smaller
      in diameter with working channels and improved optical definition. Currently, the
      role of MD is best defined in the management of SND facilitating targeted
      surgical excision, potentially avoiding unnecessary surgery, and limiting the
      extent of surgical resection for benign disease. The role of MD in breast-cancer
      screening and breast conservation surgery has yet to be fully defined. Few
      prospective randomized trials exist in the literature, and these would be crucial
      to validate current opinion, not only in the benign setting but also in breast
      oncologic surgery.

PMID- 21170662
TI  - Experience with flexible stapling techniques in laparoscopic and conventional
      surgery.
AB  - BACKGROUND: Currently, advanced minimal-access surgery cannot be realized without
      the application of modern stapling devices. The introduction of stapling devices
      with a flexible shaft and computer-assisted steering abilities was followed by
      the technical basis to provide just these features. This study aimed to assess
      the clinical application of stapling devices connected to a flexible shaft
      supported by a computer-assisted drive for maneuvering the system and to study
      its feasibility, learning curve problems, and clinical safety criteria regarding
      morbidity of the patients. METHODS: The experience with laparoscopic and open
      gastrointestinal and colorectal surgery was evaluated. Patients with esophageal,
      gastric, and colorectal diseases were selected. The stapling system consisted of
      a power console connected to a flexible shaft and a remote control unit. On the
      tip of the flexible shaft stapler, loading units could be attached and operated
      by the remote control. A circular loading unit, size 29 mm, was used for
      esophageal, gastric, and rectal anastomoses. The linear stapler (length, 55/75
      mm) was applied for the gastric tube after esophageal resection, for the jejunal
      pouch after total gastrectomy, and for division and closure of small bowel. It
      also was used during laparoscopic sleeve gastrectomy or laparoscopic
      fundoplication with COLLIS-gastroplasty. All data from the procedures were
      prospectively assessed and documented. A literature analysis was performed to
      compare morbidity data and leak rates with those of the current study. RESULTS:
      During an 8-year period, 394 patients (253 men and 141 women) were included in
      this study, and laparoscopic technique was performed in 52% of the cases. The
      mean age of the patients was 63 years (range, 16-93 years), and 33% of the
      patients had an American Society of Anesthesia classification of 3 or 4. A total
      of 1,258 firings were performed. The procedures included 54 esophageal
      resections, 90 gastric operations, and 197 colorectal resections. In the early
      experience, computer failures occurred for 2.9% of 173 patients (5 of 144
      cartridge firings, 3.5%). Later, the problems and leak rate dropped from the
      initial 6.6% (11/173) to 3.2% (7/221). The complication and morbidity rates were
      similar to those in the literature. The flexible system had the advantage of
      enabling stapler application in special indications such as performance of
      intraabdominal laparoscopic COLLIS-Plasty by bending the system along the
      subphrenic area. CONCLUSIONS: Application of the described stapling system was
      thought to be advantageous, especially for minimal-access surgery and special
      indications that required a flexible shaft. This advantage allows for
      introduction of innovative techniques in gastrointestinal and colorectal surgery.

PMID- 21170663
TI  - Follow-up period of 13 years after endoscopic total extraperitoneal repair of
      inguinal hernias: a cohort study.
AB  - BACKGROUND: Endoscopic inguinal hernia repair was introduced in the Netherlands
      in the early 1990s. The authors' institution was among the first to adopt this
      technique. In this study, long-term hernia recurrence among patients treated by
      the total extraperitoneal (TEP) approach for an inguinal hernia is described. A
      cohort study was conducted. METHODS: Between January 1993 and December 1997, 346
      TEP hernia repairs were performed for 318 patients. After a mean follow-up period
      of 13-years, a senior resident examined each patient. An experienced surgeon
      subsequently examined the patients with a diagnosis of recurrent hernia. Data
      were collected on an intention-to-treat basis, meaning that conversions were
      included in the analysis. Univariant tests were used to analyze age older than 50
      years, chronic obstructive pulmonary disease, body mass index, smoking habit,
      hernia type, history of open hernia repair, conversion, and surgeon as potential
      risk factors. RESULTS: The analysis included 191 patients (62%) with 213 hernias.
      Of the original 318 patients, 59 patients died, and 68 were lost to follow-up
      evaluation. Perioperatively, 105 lateral, 55 medial, and 53 pantalon hernias were
      observed. Of the 213 hernias, 176 were primary and 37 were recurrent. The overall
      recurrence rate was 8.9% (8.5% for primary and 10.8% for recurrent hernias). Of
      the total study group, 48% of the patients experienced a bilateral inguinal
      hernia during their lifetime. No predicting factor for recurrent hernia could be
      identified. CONCLUSIONS: The current long-term results for TEP repair of primary
      and secondary inguinal hernia show an overall recurrence rate of 8.9%, which is
      slightly higher than in previous studies. The thorough examination at follow-up
      assessment, the learning curve effect, and the intention-to-treat-analysis may
      have influenced the observed recurrence rate. Also, the percentage of bilateral
      hernias was higher than known to date. Therefore, examination of the
      contralateral side should be standard procedure.

PMID- 21170664
TI  - Hepatic and pulmonary nodular lesions in pediatric urinary tract infections.
AB  - One of the major goals in investigating children with urinary tract infection
      (UTI) is to recognize patients at risk of further UTI-related problems. This
      study reports the clinical features of 19 pediatric patients with UTIs in whom
      associated hepatic and/or pulmonary nodules were incidentally diagnosed by the
      imaging tests performed for the UTI. Hepatic nodules in five patients were
      detected on ultrasound scans, and pulmonary nodules and both hepatic and
      pulmonary nodules were detected in 12 and two children by dimercaptosuccinic acid
      scintigraphy. The mean age of the patients was 24.5 months. Vesicoureteral reflux
      (VUR) was detected in nine of 17 patients (52.9%), acute pyelonephritis was
      identified in nine of 18 patients, and renal scarring was found in 57.1% patients
      with pyelonephritis. On follow-up, the hepatic and/or pulmonary nodules regressed
      in all patients. About 85.7% of patients experienced a recurrence of UTI within 1
      year. In comparison with age- and sex-matched controls with UTIs without
      pulmonary or hepatic nodules, the presence of VUR and the recurrence of UTI
      within 1 year were higher in patients with UTIs and nodules (P<0.05). The hepatic
      and/or pulmonary nodules identified on the ultrasound scan and by
      dimercaptosuccinic acid scintigraphy may provide a valuable diagnostic marker for
      the proper management of patients with an UTI.

PMID- 21170665
TI  - Triggered electromyography for placement of thoracic pedicle screws: is it
      reliable?
AB  - Reliable electromyography (EMG) thresholds for detecting medial breaches in the
      thoracic spine are lacking, and there is a paucity of reports evaluating this
      modality in patients with adolescent idiopathic scoliosis (AIS). This
      retrospective analysis evaluates the ability of triggered EMG to detect medial
      breaches with thoracic pedicle screws in patients with AIS. We reviewed 50
      patients (937 pedicle screws) undergoing posterior spinal fusion (PSF) with
      intraoperative EMG testing. Postoperative CT scans were used for breach
      identification, and EMG values were analyzed. There were 47 medial breaches noted
      with a mean threshold stimulus of 10.2 mA (milliamperes). Only 8/47 breaches
      stimulated at 2-6 mA. Thirteen of the forty-seven screws tested at an EMG value
      <=6 mA and/or a decrease of >=65% compared with intraosseously placed screws. The
      sensitivity and positive predictive value for EMG was 0.28 and 0.21. A
      subanalysis of T10-T12 screws identified six of seven medial breaches. Using
      guidelines from the current literature, EMG does not appear to be reliable in
      detecting medial breaches from T2 to T9 but may have some utility from T10 to
      T12.

PMID- 21170666
TI  - Colour cues or spatial cues? Context-dependent preferences in the European
      greenfinch (Carduelis chloris).
AB  - Using featural cues such as colour to identify ephemeral food can increase
      foraging efficiency. Featural cues may change over time however; therefore,
      animals should use spatial cues to relocate food that occurs in a temporally
      stable position. We tested this hypothesis by measuring the cue preferences of
      captive greenfinches Carduelis chloris when relocating food hidden in a foraging
      tray. In these standardised associative learning trials, greenfinches favoured
      colour cues when returning to a foraging context that they had encountered before
      only once ("one-trial test") but switched to spatial cues when they had
      encountered that scenario on ten previous occasions ("repeated-trial test"). We
      suggest that repeated encounters generated a context in which individuals had a
      prior expectation of temporal stability, and hence context-dependent cue
      selection. Next, we trained birds to find food in the absence of colour cues but
      tested them in the presence of visual distracters. Birds were able to learn
      spatial cues after one encounter, but only when visual distracters were identical
      in colouration. When a colourful distracter was present in the test phase, cue
      selection was random. Unlike the first one-trial test, birds were not biased
      towards this colourful visual distracter. Together, these results suggest that
      greenfinches are able to learn both cue types, colour cue biases represent
      learning, not simply distraction, and spatial cues are favoured over colour cues
      only in temporally stable contexts.

PMID- 21170668
TI  - Anoikis induction and metastasis suppression by a new integrin alphavbeta3
      inhibitor in human melanoma cell line M21.
AB  - Integrin alphavbeta3 plays a critical role in the survival and metastasis process
      of cancer cells. It is therefore desirable to develop new types of small molecule
      inhibitors of integrin alphavbeta3. IH1062 (3, 5-dichloro-phenylbiguanide) is a
      novel small molecule inhibitor of integrin alphavbeta3 that we have recently
      discovered. In this study, we investigated the induction effects of anoikis in
      human melanoma cell line M21 by IH1062, by detecting caspase activity, measuring
      the expression levels of apoptosis-related proteins, and performing the
      AnnexinV/PI apoptosis assay. Furthermore, we established a melanoma pulmonary
      metastasis mouse model in order to evaluate the suppression of metastasis by
      IH1062 in vivo. Our results demonstrate that IH1062 triggered human melanoma M21
      cells to undergo anoikis by interrupting the attachment of M21 cells to
      extracellular matrix, reducing the phosphorylation of focal adhesion kinase,
      decreasing survivin and the ratio of Bcl-2/Bax proteins, and activating caspase
      cascades in vitro. Additionally, IH1062 showed markedly anti-metastatic effects
      in the pulmonary metastasis model in vivo, which makes it a promising lead to
      develop new drugs for anti-metastasis therapies.

PMID- 21170669
TI  - A phase I/II study of the Src inhibitor saracatinib (AZD0530) in combination with
      gemcitabine in advanced pancreatic cancer.
AB  - AIM: This phase I/II study of saracatinib in combination with gemcitabine in
      patients with advanced pancreatic cancer was conducted by the NCIC Clinical
      Trials Group. The aims were to define the recommended phase II dose (RP2D) of
      saracatinib when combined with gemcitabine, and assess the efficacy of this
      combination in advanced pancreatic cancer. PATIENTS AND METHODS: Eligibility
      criteria included locally advanced or metastatic pancreatic adenocarcinoma and no
      prior chemotherapy. In phase I saracatinib was escalated in combination with
      gemcitabine (1000 mg/m(2)) to determine the recommended phase II dose (RP2D). The
      study was then expanded to a single arm phase II trial using a Simon 2-stage
      design. The primary endpoint was objective tumor response (OR) plus stable
      disease >= 4 months (SD4) rate; if >= 8 patients had OR+SD4, the study would
      proceed to stage 2. RESULTS: Thirteen patients were enrolled into the phase I
      portion of this study. Saracatinib 175 mg PO daily was chosen as the RP2D in
      combination with gemcitabine. Twenty-one additional patients were then enrolled
      at the RP2D (phase II). Of the 22 response evaluable patients treated at the
      RP2D, 9 patients (40.9%) had progressive disease, 6 patients (27.3%) had stable
      disease for less than 4 months, 5 patients (22.7%) had SD4, and 2 patients (9.1%)
      had a partial response to treatment. Objective criteria for continuing to stage 2
      were thus not met and the trial was closed following the accrual of 34 patients.
      CONCLUSION: Saracatinib 175 mg daily in combination with gemcitabine is well
      tolerated but the combination did not improve efficacy over what would be
      expected from gemcitabine alone.

PMID- 21170670
TI  - Optimization of amino acid type-specific 13C and 15N labeling for the backbone
      assignment of membrane proteins by solution- and solid-state NMR with the UPLABEL
      algorithm.
AB  - We present a computational method for finding optimal labeling patterns for the
      backbone assignment of membrane proteins and other large proteins that cannot be
      assigned by conventional strategies. Following the approach of Kainosho and Tsuji
      (Biochemistry 21:6273-6279 (1982)), types of amino acids are labeled with (13)C
      or/and (15)N such that cross peaks between (13)CO(i - 1) and (15)NH(i) result
      only for pairs of sequentially adjacent amino acids of which the first is labeled
      with (13)C and the second with (15)N. In this way, unambiguous sequence-specific
      assignments can be obtained for unique pairs of amino acids that occur exactly
      once in the sequence of the protein. To be practical, it is crucial to limit the
      number of differently labeled protein samples that have to be prepared while
      obtaining an optimal extent of labeled unique amino acid pairs. Our computer
      algorithm UPLABEL for optimal unique pair labeling, implemented in the program
      CYANA and in a standalone program, and also available through a web portal, uses
      combinatorial optimization to find for a given amino acid sequence labeling
      patterns that maximize the number of unique pair assignments with a minimal
      number of differently labeled protein samples. Various auxiliary conditions,
      including labeled amino acid availability and price, previously known partial
      assignments, and sequence regions of particular interest can be taken into
      account when determining optimal amino acid type-specific labeling patterns. The
      method is illustrated for the assignment of the human G-protein coupled receptor
      bradykinin B2 (B(2)R) and applied as a starting point for the backbone assignment
      of the membrane protein proteorhodopsin.

PMID- 21170671
TI  - Fluorescence property of ZnO nanoparticles and the interaction with bromothymol
      blue.
AB  - We synthesized ZnO quantum dots (QDs) simply in alcoholic solution, and
      investigated the interaction between ZnO QDs and bromothymol blue. The
      structural, morphological, size and spectral properties of ZnO QDs were studied.
      It was found that ZnO QDs were spherical nanoparticles in the crystal structure,
      and the average diameter of ZnO QDs was about 4.8 nm. The excitation and emission
      peaks were located at 346 nm and 520 nm, respectively, which were obtained on a
      common fluorophotometer. The quantum yield of ZnO QDs was obtained by using
      quinine sulfate as a reference reagent. In addition, the fluorescence of ZnO QDs
      can be quenched by bromothymol blue, and the quenching mechanism was proposed in
      a dynamic quenching mode.

PMID- 21170672
TI  - The role of peer stress and pubertal timing on symptoms of psychopathology during
      early adolescence.
AB  - Stress is known to amplify the link between pubertal timing and psychopathology.
      However, few studies have examined the role of peer stress as a context for this
      link. The present study examined the interaction between perceived pubertal
      timing and peer stress on symptoms of psychopathology in early adolescence. The
      sample consisted of 264 students (63% female; M (age) = 12.40, SD = 1.00; 55%
      Caucasian, 23% African American, 7% Latino, 11% biracial and 4% other). Higher
      peer stress was associated with symptoms of anxiety/depression; this effect did
      not vary by timing or gender. However, early-maturing girls with high peer stress
      demonstrated higher rates of relational and overt aggression compared to other
      girls. Findings also suggested that late-maturing boys with high stress are at
      risk for aggression problems; however, due to the small number of boys, analyses
      were exploratory. Overall, results suggest that developmentally salient contexts
      as indicated by stressful peer experiences may pose unique threats to early
      maturing girls and possibly late-maturing boys.

PMID- 21170673
TI  - Redistribution of tight junction proteins during EPEC infection in vivo.
AB  - Enteropathogenic Escherichia coli (EPEC) is a leading cause of diarrhea among
      infants. Tight junction plays a vital role in intestinal paracellular
      permeability by forming physical intercellular barriers in epithelial cells.
      However, the impact of this enteric pathogen on tight junctions in vivo has not
      been fully investigated. In the present study, the alterations in tight junctions
      following EPEC infection in vivo were investigated. Western blot analysis
      revealed that the tight junction proteins, occludin and claudin-1, were displaced
      from tight junction membrane microdomains to Triton X-100 soluble fractions after
      EPEC infection. Changes in intestinal paracellular permeability were determined
      using the molecular tracer biotin, which was observed to penetrate the epithelia
      and extended into the lamina propria, indicating disruption in tight junction
      barrier function. Our results suggested that redistribution of tight junction
      proteins plays an important role in the disruption of epithelial barrier function
      induced by EPEC infection, which may provide new insight into the pathogenesis of
      diarrhea caused by EPEC.

PMID- 21170674
TI  - Psychotropic medications in autism: practical considerations for parents.
AB  - Medications are widely prescribed in children with autism spectrum disorders.
      Most commonly these medications are used to decrease symptoms that fall under
      three main clusters: irritability, ADHD-like symptoms, and repetitive behaviors.
      In this guide we introduce basic approaches to medications in children with
      autism and review the scientific evidence in each symptom cluster.

PMID- 21170675
TI  - Role of PTEN promoter methylation in tamoxifen-resistant breast cancer cells.
AB  - Tamoxifen (TAM) resistance is a serious clinical problem in the treatment of
      breast cancer. Here, we found that S-adenosylmethionine (SAM) and DNA
      methyltransferase1 (DNMT1) expression are up-regulated in TAM-resistant breast
      cancer (TAMR-MCF-7) cells. We further focused on whether increased SAM with DNMT1
      overexpression in TAMR-MCF-7 cells lead to aberrant methylation of the PTEN gene
      promoter and its therapeutic potential. Methylation-specific PCR analyses
      revealed that two sites within the PTEN promoters were methylated in TAMR-MCF-7
      cells, which resulted in down-regulation of PTEN expression and increase in Akt
      phosphorylation. Both the loss of PTEN expression and the increased Akt
      phosphorylation in TAMR-MCF-7 cells were completely reversed by 5-aza-2'
      deoxycytidine (5-Aza), a DNMT inhibitor. 5-Aza inhibited the basal cell
      proliferation rate of TAMR-MCF-7 cells and intraperitoneal injection of 5-Aza
      significantly suppressed TAMR-MCF-7 tumor growth in a xenograft study.
      Immunohistochemistry showed that PTEN expression in TAM-resistant human breast
      cancer tissues was lower than in TAM-responsive cases. These results suggest that
      methylation of the PTEN promoter related to both SAM increase and DNMT1
      activation contributes to persistent Akt activation and are potential therapeutic
      targets for reversing TAM resistance in breast cancer.

PMID- 21170677
TI  - Oral administration of benzyl-isothiocyanate inhibits solid tumor growth and lung
      metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice.
AB  - Benzyl-isothiocyanate (BITC) is a hydrolysis product of glucotropaeolin, a
      compound found in cruciferous vegetables, and has also been shown to have anti
      tumor properties. To evaluate the effects of BITC administration on the tumor
      growth and metastasis of breast cancer, 4T1 murine mammary carcinoma cells were
      injected into the inguinal mammary fat pads of syngeneic female BALB/c mice. One
      day later, the mice were subjected to gavage for 4 weeks with BITC (0, 5, or 10
      mg/kg body weight/day). Oral BITC treatment induced a significant reduction in
      the growth of solid tumors. BITC reduced hemoglobin contents and CD31 and
      vascular endothelial growth factor (VEGF) expression in the tumors, as well as
      circulating levels of VEGF. Reduced expressions of proliferating cell nuclear
      antigen and cyclin-dependent kinase 4 were noted in the tumors of BITC-treated
      mice. BITC markedly increased the numbers of apoptotic cells with increased Bax
      expression, cleaved caspase-3, and PARP levels, but reduced Bcl-2 expression in
      tumor tissues. In addition, BITC was shown to reduce the numbers of pulmonary
      tumor nodules and the total pulmonary metastatic volume. BITC induced a
      significant reduction in the levels of matrix metalloproteinase (MMP)-2, MMP-9,
      tissue inhibitor of metalloproteinase (TIMP)-1, and urokinase-type plasminogen
      activator in the sera and lungs of 4T1 cell-injected mice. However, the
      concentrations of TIMP-2 and plasminogen activator inhibitor-1 were increased in
      the sera and lungs of BITC-treated mice. The results of this study indicate that
      BITC has potential as a preventive agent for metastatic breast cancer.

PMID- 21170676
TI  - Tetra-methoxystilbene modulates ductal growth of the developing murine mammary
      gland.
AB  - Extensive data suggest that estradiol contributes to the development of breast
      cancer by acting as a mitogen and exerting direct genotoxic effects after
      enzymatic conversion to 4-hydroxyestradiol (4-OHE2) via cytochrome P450 1B1
      (CYP1B1). The mammary gland, ovary, and uterus all express CYP1B1. Overexpression
      of this enzyme has been associated with an increased risk of breast cancer and
      blockade might reduce this carcinogenic effect. For this reason, we conducted
      systematic in vitro and in vivo studies of a CYP1B1 inhibitor, TMS (2,3',4,5'
      tetramethoxystilbene). We found that TMS blocked the enzymatic conversion of
      radiolabeled estradiol to both 2-hydroxyestradiol (2-OHE2) and 4-OHE2, but did
      not inhibit Cyp1b1 message formation. In vivo studies using mass spectrometry
      showed that TMS inhibited formation of 2-OHE2 and 4-OHE2 and the resulting
      estrogen-DNA adducts. To examine its biologic actions in vivo, we investigated
      whether TMS could block the hyperplastic changes that occur in the developing
      breast of aromatase-transfected mice. We found that TMS induced a significant
      reduction of ductal structures in mice less than 6 months in age. In older mice,
      no reduction in breast morphology occurred. These latter studies uncovered
      unexpected estrogen agonistic actions of TMS at high doses, including a
      paradoxical stimulation of breast ductal structures and the endometrium. These
      studies suggest that the enzyme inhibitory properties of TMS, as well as the
      effects on developing breast, could implicate a role for TMS in breast cancer
      prevention, but only in low doses and on developing breast.

PMID- 21170679
TI  - Development and validation of a computational model to study the effect of foot
      constraint on ankle injury due to external rotation.
AB  - Recent studies, using two different manners of foot constraint, potted and taped,
      document altered failure characteristics in the human cadaver ankle under
      controlled external rotation of the foot. The posterior talofibular ligament
      (PTaFL) was commonly injured when the foot was constrained in potting material,
      while the frequency of deltoid ligament injury was higher for the taped foot. In
      this study an existing multibody computational modeling approach was validated to
      include the influence of foot constraint, determine the kinematics of the joint
      under external foot rotation, and consequently obtain strains in various
      ligaments. It was hypothesized that the location of ankle injury due to excessive
      levels of external foot rotation is a function of foot constraint. The results
      from this model simulation supported this hypothesis and helped to explain the
      mechanisms of injury in the cadaver experiments. An excessive external foot
      rotation might generate a PTaFL injury for a rigid foot constraint, and an
      anterior deltoid ligament injury for a pliant foot constraint. The computational
      models may be further developed and modified to simulate the human response for
      different shoe designs, as well as on various athletic shoe-surface interfaces,
      so as to provide a computational basis for optimizing athletic performance with
      minimal injury risk.

PMID- 21170678
TI  - Vascular endothelium-specific overexpression of human catalase in cloned pigs.
AB  - The objective of this study was to develop transgenic Yucatan minipigs that
      overexpress human catalase (hCat) in an endothelial-specific manner. Catalase
      metabolizes hydrogen peroxide (H(2)O(2)), an important regulator of vascular tone
      that contributes to diseases such as atherosclerosis and preeclampsia. A large
      animal model to study reduced endothelium-derived H(2)O(2) would therefore
      generate valuable translational data on vascular regulation in health and
      disease. Yucatan minipig fetal fibroblasts stably co-transfected with human
      catalase (Tie2-hCat) and eGFP expression constructs were isolated into single
      cell populations. The presence of the Tie2-hCat transgene in individual colonies
      of fibroblasts was determined by PCR. Transgenic fibroblasts were used for
      nuclear transfer into enucleated oocytes by electrofusion. A minimum of 140
      cloned embryos were transferred per surrogate sow (n = 4). All four surrogates
      maintained pregnancies and piglets were delivered by cesarean section. Nine male
      piglets from three of the four litters carried the Tie2-hCat transgene.
      Expression of human catalase mRNA and overall elevated catalase protein in
      isolated umbilical endothelial cells from transgenic piglets were verified by RT
      PCR and western blot, respectively, and endothelial localization was confirmed by
      immunohistochemistry. Increased enzymatic activity of catalase in transgenic
      versus wild-type endothelial cells was inferred based on significantly reduced
      levels of H(2)O(2) in culture. The similarities in swine and human cardiovascular
      anatomy and physiology will make this pig model a valuable source of information
      on the putative role of endothelium-derived H(2)O(2) in vasodilation and in the
      mechanisms underlying vascular health and disease.

PMID- 21170680
TI  - Toxic response caused by a misfolding variant of the mitochondrial protein short
      chain acyl-CoA dehydrogenase.
AB  - BACKGROUND: Variations in the gene ACADS, encoding the mitochondrial protein
      short-chain acyl CoA-dehydrogenase (SCAD), have been observed in individuals with
      clinical symptoms. The phenotype of SCAD deficiency (SCADD) is very
      heterogeneous, ranging from asymptomatic to severe, without a clear genotype
      phenotype correlation, which suggests a multifactorial disorder. The
      pathophysiological relevance of the genetic variations in the SCAD gene is
      therefore disputed, and has not yet been elucidated, which is an important step
      in the investigation of SCADD etiology. AIM: To determine whether the disease
      associated misfolding variant of SCAD protein, p.Arg107Cys, disturbs
      mitochondrial function. METHODS: We have developed a cell model system, stably
      expressing either the SCAD wild-type protein or the misfolding SCAD variant
      protein, p.Arg107Cys (c.319 C > T). The model system was used for investigation
      of SCAD with respect to expression, degree of misfolding, and enzymatic SCAD
      activity. Furthermore, cell proliferation and expression of selected stress
      response genes were investigated as well as proteomic analysis of mitochondria
      enriched extracts in order to study the consequences of p.Arg107Cys protein
      expression using a global approach. CONCLUSIONS: We found that expression of the
      p.Arg107Cys variant SCAD protein gives rise to inactive misfolded protein
      species, eliciting a mild toxic response manifested though a decreased
      proliferation rate and oxidative stress, as shown by an increased demand for the
      mitochondrial antioxidant SOD2. In addition, we found markers of apoptotic
      activity in the p.Arg107Cys expressing cells, which points to a possible
      pathophysiological role of this variant protein.

PMID- 21170681
TI  - Heparin cofactor II-thrombin complex and dermatan sulphate:chondroitin sulphate
      ratio are biomarkers of short- and long-term treatment effects in
      mucopolysaccharide diseases.
AB  - Early detection of mucopolysaccharidosis (MPS) is an important factor in
      treatment success; therefore, good disease biomarkers are vital. We evaluate
      heparin cofactor II-thrombin complex (HCII-T) as a biomarker in serum and dried
      blood spots (DBS) of MPS patients. Serum HCII-T and urine dermatan
      sulphate:chondroitin sulphate (DS:CS) ratio are also compared longitudinally
      against clinical outcomes in MPSI, II and VI patients following treatment.
      Samples were collected from MPS patients at the Royal Manchester Children's
      Hospital. DS:CS ratio was obtained by measuring the area density of spots from 2D
      electrophoresis of urinary glycosaminoglycans. Serum and DBS HCII-T was measured
      by sandwich ELISA. Serum HCII-T is elevated approximately 25-fold in MPS diseases
      that store DS, clearly distinguishing untreated MPSI, II and VI patients from
      unaffected age-matched controls. Serum HCII-T is also elevated in MPSIII, which
      leads to storage of heparan sulphate, with an increase of approximately 4-fold
      over unaffected age-matched controls. Urine DS:CS ratio and serum HCII-T decrease
      in response to treatment of MPSI, II and VI patients. HCII-T appears to respond
      rapidly to perturbations in treatment, whilst DS:CS ratio responds more slowly.
      HCII-T is a suitable biomarker for MPSI, II and VI, and it may also be
      informative for MPS diseases storing HS alone, such as MPSIII, although the
      elevation observed is smaller. In treated MPS patients, HCII-T and DS:CS ratio
      appear to measure short-term and long-term treatment outcomes, respectively. The
      potential value of HCII-T measurement in DBS for newborn screening of MPS
      diseases warrants further investigation.

PMID- 21170682
TI  - Psychosocial interventions to improve quality of life in prostate cancer
      survivors and their intimate or family partners.
AB  - PURPOSE: The primary purpose was to test the effectiveness of two telephone
      delivered psychosocial interventions for maintaining and improving quality of
      life (QOL) (psychological, physical, social, and spiritual well-being) among 71
      prostate cancer survivors and the 70 intimate or family partners who were
      supporting them in their recovery. METHODS: This study used a three-wave repeated
      measures experimental design. Both the interpersonal counseling intervention (TIP
      C) and health education attention condition (HEAC) were delivered using the
      telephone. RESULTS: Improvements in depression, negative affect, stress, fatigue,
      and spiritual well-being were significantly higher for survivors in the HEAC than
      for those in the TIP-C condition. Partners in the HEAC condition showed
      significantly greater improvements in depression, fatigue, social support from
      family members, social well-being, and spiritual well-being compared to partners
      in the TIP-C condition. The results revealed superior outcomes for those assigned
      to the HEAC intervention. CONCLUSIONS: The psychosocial interventions in this
      study were effective in maintaining or improving the QOL for prostate cancer
      survivors and their partners. Both the survivor and their intimate partner or
      family member benefitted from the interventions. Future research is needed to
      determine the optimal timing and client characteristics for each intervention.

PMID- 21170683
TI  - Axial rigidity and quality of life in patients with Parkinson's disease: a
      preliminary study.
AB  - PURPOSE: Rigidity is a cardinal symptom of Parkinson's disease (PD) and is often
      clinically assessed by passively flexing and extending a patient's limb.
      Objective measurements had been employed to examine rigidity in PD subjects,
      including wrist, elbow, knee and trunk. This study aimed to investigate the
      relationship between an objective measurement of trunk rigidity and health
      related quality of life (HRQoL) and functional status in patients with mild to
      moderate PD. METHODS: An isokinetic dynamometer Biodex System 3 was employed to
      assess trunk rigidity in 36 PD patients. HRQoL was assessed with the EuroQol-5D
      and Parkinson's Disease Questionnaire-39 items (PDQ-39). Functional status was
      measured with the Schwab and England scale. RESULTS: Trunk rigidity was
      correlated with the HRQoL assessed with the mobility, cognition and stigma PDQ-39
      domains and the total PDQ-39 scores. No correlations were found among trunk
      muscle tone assessed with the isokinetic dynamometer and the EuroQoL-5D.
      Functional status was correlated with the trunk extensors rigidity at all angular
      velocities. CONCLUSION: The results from this study suggest that the axial motor
      impairments impact on QoL and functional status in patients with PD. Further
      studies are needed with quantitative devices for axial rigidity assessment to
      determine the relationship between trunk rigidity in PD patients with higher
      disease severity and HRQoL scales.

PMID- 21170685
TI  - Intragastric balloon treatment for obesity: results of a large single center
      prospective study.
AB  - BACKGROUND: The intragastric balloon is a widely used method in the treatment of
      obesity indicated for those patients who have failed to achieve and maintain the
      weight loss with conventional measures or for preparation of patients who are
      candidates for bariatric surgery. METHODS: From April 2007 to April 2009, 171
      consecutive patients (111 females, 60 males; mean age 39.2 +/- 10.5, mean weight
      123.2 +/- 27.1 kg) were evaluated before and 6 months after bioenteric
      intragastric balloon (BIB) placement by assessment of anthropometric and
      biochemical parameters. RESULTS: The mean BMI during balloon treatment declined
      from 41.9 +/- 7.3 to 36.0 +/- 7.9 kg/m2 (p < 0.001) with a percentage of excess
      weight loss of 39.7 +/- 23.6 and percentage of excess body mass index loss of
      39.5 +/- 25.1. A significant improvement in blood pressure, glycemia, and
      triglyceride level but not in total cholesterol, high-density lipoprotein, and
      low-density lipoprotein cholesterol levels was seen. CONCLUSION: Results of this
      large prospective single center study confirmed that intragastric balloon is
      useful and safe method for promoting weight loss. Due to improvement of metabolic
      parameters, treatment with BIB results in reduction of cardiovascular risk and
      provides a sustained benefit on liver function in obese patients.

PMID- 21170684
TI  - Postprandial antioxidant effect of the Mediterranean diet supplemented with
      coenzyme Q10 in elderly men and women.
AB  - Postprandial oxidative stress is characterized by an increased susceptibility of
      the organism towards oxidative damage after consumption of a meal rich in lipids
      and/or carbohydrates. We have investigated whether the quality of dietary fat
      alters postprandial cellular oxidative stress and whether the supplementation
      with coenzyme Q(10) (CoQ) lowers postprandial oxidative stress in an elderly
      population. In this randomized crossover study, 20 participants were assigned to
      receive three isocaloric diets for periods of 4 week each: (1) Mediterranean diet
      supplemented with CoQ (Med+CoQ diet), (2) Mediterranean diet (Med diet), and (3)
      saturated fatty acid-rich diet (SFA diet). After a 12-h fast, the volunteers
      consumed a breakfast with a fat composition similar to that consumed in each of
      the diets. CoQ, lipid peroxides (LPO), oxidized low-density lipoprotein (oxLDL),
      protein carbonyl (PC), total nitrite, nitrotyrosine plasma levels, catalase,
      superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities and
      ischemic reactive hyperaemia (IRH) were determined. Med diet produced a lower
      postprandial GPx activity and a lower decrease in total nitrite level compared to
      the SFA diet. Med and Med+CoQ diets induced a higher postprandial increase in IRH
      and a lower postprandial LPO, oxLDL, and nitrotyrosine plasma levels than the SFA
      diet. Moreover, the Med+CoQ diet produced a lower postprandial decrease in total
      nitrite and a greater decrease in PC levels compared to the other two diets and
      lower SOD, CAT, and GPx activities than the SFA diet.In conclusion, Med diet
      reduces postprandial oxidative stress by reducing processes of cellular oxidation
      and increases the action of the antioxidant system in elderly persons and the
      administration of CoQ further improves this redox balance.

PMID- 21170686
TI  - Gene expression, function and ischemia tolerance in male and female rat hearts
      after sub-toxic levels of angiotensin II.
AB  - To examine the response to chronic high-dose angiotensin II (Ang II) and a
      proposed milder response in female hearts with respect to gene expression and
      ischemic injury. Female and male litter-matched rats were treated with 400 ng kg(
      1) min(-1) Ang II for 14 days. Hearts were isolated, subjected to 30-min ischemia
      and 30-min reperfusion in combination with functional monitoring and thereafter
      harvested for gene expression, WB and histology. Ang II-treated hearts showed
      signs of non-hypertrophic remodeling and had significantly higher end diastolic
      pressure after reperfusion, but no significant gender difference was detected.
      Ang II increased expression of genes related to heart function (ANF, beta-MCH,
      Ankrd-1, PKC-alpha, PKC-delta TNF-alpha); fibrosis (Col I-alpha1, Col III-alpha1,
      Fn-1, Timp1) and apoptosis (P53, Casp-3) without changing heart weight but with
      68% increase in collagen content. High (sub-toxic) dose of Ang II resulted in
      marked heart remodeling and diastolic dysfunction after ischemia without
      significant myocyte hypertrophy or ventricular chamber dilatation. Although there
      were some gender-dependent differences in gene expression, female gender did not
      protect against the overall response.

PMID- 21170687
TI  - The monoclonal CCR5 antibody PRO-140: the promise of once-weekly HIV therapy.

PMID- 21170688
TI  - Inpatient enteral and parenteral [corrected] nutrition for patients with
      diabetes.
AB  - Both glycemic control and adequate nutrition support impact the clinical outcome
      of hospitalized patients. Providing nutrition to malnourished patients using the
      enteral or parenteral route may increase the risk of hyperglycemia, especially in
      patients with diabetes. Hyperglycemia can be managed through the use of enteral
      tube feeds with reduced carbohydrate content or limiting the carbohydrate
      concentration in parenteral formulas. Judicious use of insulin or other glucose
      lowering medications synchronized with appropriate nutrition support allows for
      optimal inpatient glycemic control.

PMID- 21170689
TI  - Clinical usefulness of temporal subtraction method in screening digital chest
      radiography with a mobile computed radiography system.
AB  - The temporal subtraction image which is obtained by subtraction of a previous
      image from a current image of the same patient can enhance interval changes. In
      this study, we applied the temporal subtraction method for lung cancer screening
      and evaluated the clinical usefulness by comparing the review time and the
      detection accuracy of lung cancers without and with subtraction images. Since
      1996, we have been performing screening chest radiography for a mass survey of
      lung cancers in the Iwate Prefecture, Japan, by using a van equipped with a
      computed radiography system and a digital archive system. During the 12 years
      from 1997 to 2008, a total of 186,340 examinations were performed, and 121,526
      (65.2%) temporal subtraction images were provided in the lung cancer screening.
      Twenty-four abnormal cases with lung cancer and 270 normal cases were selected
      from the lung cancer screening. Five radiologists participated in an observer
      performance study and interpreted previous and current chest radiographs without
      and with temporal subtraction images. In addition, radiologists interpreted
      previous and current images with a double-reading method. The average ROC curves
      demonstrated a significant improvement in the detection accuracy of lung cancers
      with the temporal subtraction images compared with that without the temporal
      subtraction images, and that with the double-reading method. Therefore, we
      believe strongly that the temporal subtraction method is clinically useful for
      radiologists in the detection of lung cancers in mass surveys.

PMID- 21170690
TI  - Exploring the intergenerational transmission of illness behavior: from
      observations to experimental intervention.
AB  - BACKGROUND: Functional abdominal pain (FAP) of childhood is characterized by,
      among other things, pain with no known physiological cause, and family patterns
      of related disorders have been reported. PURPOSE: The purpose of this paper is to
      trace the development of one FAP research program and highlight some of its key
      findings from observations of interaction patterns to intervention studies
      designed to test outcomes of altering these patterns. METHODS: Studies summarized
      include observational and experimental research. RESULTS: Parental response to
      child pain behaviors appears to be a key factor in the development and
      maintenance of FAP, and intervention which includes targeting changes in parental
      responses can decrease reports of pain and other illness behaviors. CONCLUSIONS:
      Research into FAP can provide valuable information for not only FAP and other
      unexplained pain conditions, but other medical conditions where environmental
      responses may play an important role in their etiology and maintenance.

PMID- 21170691
TI  - The -112G>A polymorphism of the secretoglobin 3A2 (SCGB3A2) gene encoding
      uteroglobin-related protein 1 (UGRP1) increases risk for the development of
      Graves' disease in subsets of patients with elevated levels of immunoglobulin E.
AB  - The human secretoglobin 3A2 (SCGB3A2) gene encoding secretory uteroglobin-related
      protein 1 (UGRP1) resides on the chromosome region 5q31-33 that harbors a
      susceptibility locus to several autoimmune and inflammatory diseases, including
      asthma and Graves' disease (GD). Recently, association between the marker
      rs1368408 (-112G >A), located in the promoter region of the SCGB3A2 gene, and
      susceptibility to GD was found in Chinese and UK Caucasians. The study aim was to
      evaluate whether this polymorphism confers GD susceptibility in a large
      population cohort comprising 1,474 Russian GD patients and 1,619 controls. The
      marker rs1368408 was studied using a TaqMan allele discrimination assay. Serum
      levels of UGRP1 and immunoglobulin E (IgE) were assessed using enzyme-linked
      immunosorbent assay (ELISA) analyses. Association between the allele A of SCGB3A2
      and a higher risk of GD (odds ratio [OR] = 1.33, P = 2.9 * 10(-5)) was shown.
      Both affected and non-affected carriers of the higher risk genotype A/A had
      significantly decreased levels of serum UGRP1 compared to the subjects homozygous
      for G/G (93 +/- 37 pg/ml vs. 132 +/- 45 pg/ml, P = 0.0011 for GD patients; 77 +/-
      28 pg/ml vs. 119 +/- 33 pg/ml, P = 0.0019 for controls). Serum IgE levels were
      significantly higher in non-affected subjects homozygous for A/A compared to
      control individuals homozygous for G/G (153 +/- 46 IU/ml vs. 122 +/- 40 IU/ml, P
      = 0.0095). Our data suggest that the carriage of the SCGB3A2 -112A/A variant
      increases the risk for GD in subsets of patients with elevated levels of IgE, a
      hallmark of allergic asthma. Therefore, the SCGB3A2 -112G >A polymorphism may be
      considered as a likely marker linking susceptibility to allergy/asthma and GD on
      chromosome 5q31-33.

PMID- 21170692
TI  - Interactions of Npc1 and amyloid accumulation/deposition in the APP/PS1 mouse
      model of Alzheimer's.
AB  - Although Niemann-Pick C1 disease has frequently been called "juvenile
      Alzheimer's", the effects of introducing Npc1 mutations into a mouse model of
      Alzheimer's have not previously been performed. We have crossed Npc1 (+/-) mice
      with APP/PS1 "Alzheimer's" mice and studied Abeta42 accumulation and amyloid
      plaque formation. Mice heterozygous for Npc1 and positive for the APP and PS1
      transgenes accumulated Abeta42 more rapidly than the APP/PS1 controls and this
      correlated, as expected, with the area of amyloid plaques. We conclude that the
      alterations of intracellular cholesterol present in Npc1 (+/-) mice can influence
      the progress of Alzheimer's disease in the APP/PS1 mouse model.

PMID- 21170693
TI  - [Phytotherapy 2010 in a changed environment].

PMID- 21170694
TI  - Ginkgo biloba in Alzheimer's disease: a systematic review.
AB  - This systematic review determines the benefit of treatment with Ginkgo biloba
      (Ginkgo) in Alzheimer's disease (AD) concerning patient-relevant outcomes.
      Bibliographic databases, clinical trial and study result registries were searched
      for randomized controlled trials (RCTs) in patients with AD (follow-up >=16
      weeks) comparing Ginkgo to placebo or a different treatment option. Manufacturers
      were asked to provide unpublished data. If feasible, data were pooled by meta
      analysis. Six studies were eligible; overall, high heterogeneity was shown for
      most outcomes, except safety aspects. Among studies administering high-dose
      Ginkgo (240 mg), all studies favour treatment though effects remain
      heterogeneous. In this subgroup, a benefit of Ginkgo exists for activities of
      daily living. Cognition and accompanying psychopathological symptoms show an
      indication of a benefit. A harm of Ginkgo is not evident. An estimation of the
      effect size was not possible for any outcome. Further evidence is needed which
      focuses especially on subgroups of AD patients.

PMID- 21170695
TI  - Efficacy and safety of silexan, a new, orally administered lavender oil
      preparation, in subthreshold anxiety disorder - evidence from clinical trials.
AB  - We review the data on the efficacy and tolerability of silexan, a novel
      preparation from lavender oil for oral use, in the treatment of anxiety disorders
      and related condition with particular attention to subthreshold generalized
      anxiety disorder (GAD). Three randomized, double-blind clinical trials were
      identified which investigated the efficacy of silexan in subsynromal anxiety
      disorder (vs. placebo; 10 weeks' treatment), in GAD (vs. lorazepam; 6 weeks), and
      in restlessness and agitation (vs. placebo; 10 weeks) according to DSM-IV and ICD
      10 criteria. All trials assessed the participants' anxiety levels using the
      Hamilton Anxiety Scale (HAMA). Across all trials 280 patients were exposed to
      silexan 80 mg/day, 37 were treated with lorazepam 0.5 mg/day and 192 received
      placebo. Average within group HAMA total scores at baseline ranged between 24.7
      and 27.1 points. Patients treated with silexan showed average HAMA total score
      decreases by between 10.4 +/- 7.1 and 12.0 +/- 7.2 points at week 6 and by
      between 11.8 +/- 7.7 and 16.0 +/- 8.3 points at week 10. In GAD silexan and
      lorazepam showed comparable HAMA total score reductions (90% CI for mean value
      difference: -2.3; 2.8 points).

PMID- 21170696
TI  - [The HMPC monograph on Hypericum: Background, development, contents].
AB  - The adoption of the EU community monograph on Hypericum constitutes a milestone
      in the process of harmonisation of herbal medicinal products within the European
      Community. The assessment of the published clinical data revealed that for two
      types of extracts the evidence of the efficacy in mild to moderate depressive
      episodes compared to placebo or standard medication was found to be acceptable.
      Additionally, a sufficient efficacy in relapse prophylaxis could be demonstrated
      for these two herbal preparations. For some other dry extracts, the efficacy in
      the short-term treatment of symptoms in mild depressive disorders was found to be
      substantiated. Short-term treatment with preparations containing low amounts of
      hyperforin did not increase cytochrome P450 enzyme activity. Therefore the oral
      administration of traditional herbal preparations is restricted to two weeks. In
      the case that an applicant demonstrates that the daily intake of hyperforin is
      below 1 mg the warnings on interactions may be omitted in traditional herbal
      medicinal products. Additionally the cutaneous administration of traditional
      liquid herbal preparations for the traditional use in symptomatic treatment of
      minor inflammations of the skin and as an aid in healing minor wounds was
      included in the monograph.

PMID- 21170697
TI  - [Pelargonium sidoides in acute bronchitis - Health-related quality of life and
      patient-reported outcome in adults receiving EPs 7630 treatment].
AB  - Health-related quality of life (HRQL) and patient-reported outcome (PRO) have
      become important outcome parameters for the evaluation of medical treatment
      within clinical trials and, furthermore, to evaluate efficiency in clinical
      practice. We therefore report further exploratory results of an already reported
      dose-finding study with EPs 7630 tablets, now focussing on HRQL and PRO. A total
      of 406 adults with acute bronchitis were randomly assigned to one of four
      parallel treatment groups (placebo, 30 mg, 60 mg or 90 mg EPs 7630 daily). HRQL
      and PRO were assessed by questionnaires as secondary outcome measures at each
      study visit or daily in the patient's diary. At day 7, the patient-reported
      outcome measures were significantly more improved in all the three EPs 7630
      groups compared to placebo (EQ-5D and EQ VAS, SF-12: physical score, impact of
      patient's sickness, duration of activity limitation, patient-reported treatment
      outcome, satisfaction with treatment). In conclusion, a statistically significant
      and clinically relevant improvement of HRQL/PRO compared to placebo was shown in
      all the three EPs 7630 groups.

PMID- 21170699
TI  - [Austrian guidance for the pharmacologic treatment of osteoporosis in
      postmenopausal women: Addendum 2010].
AB  - The Austrian Society for Bone and Mineral Research routinely publishes evidence
      based guidelines for the treatment of postmenopausal osteoporosis. The fully
      human monoclonal antibody denosumab (Prolia((r))) has been recently approved by
      the European Medical Agency (EMEA) and the Food and Drug Administration (FDA) for
      the treatment of postmenopausal osteoporosis. Denosumab has been shown to reduce
      vertebral, non-vertebral,and hip-fracture risk effectively. Together with
      alendronate, risedronate, zoledronate, ibandronate, strontium ranelate, and
      raloxifene, denosumab constitutes an effective option in the treatment of
      postmenopausal osteoporosis.

PMID- 21170698
TI  - [Pharmacokinetic drug interactions by herbal drugs: Critical evaluation and
      clinical relevance].
AB  - Pharmacokinetic herb-drug interactions are caused by an induction or inhibition
      of cytochrome P450 (CYP) enzymes or transporters e.g. P-glycoprotein. St. John's
      wort extracts containing hyperforin increase the expression of CYP-enzymes and P
      glycoprotein mainly in the gut and liver which leads to a clinically relevant
      decrease of the bioavailability of CYP and P-glycoprotein substrates. Contrarily,
      the bioactivation of the prodrug losartan is reduced by milk thistle extracts
      which is due to an inhibition of CYP2C9. However, the 15 % reduction of the
      bioavailability of the active metabolite E-3174 is clinically not relevant. Also,
      minor changes in drug bioavailability observed in clinical studies for valerian,
      echinacea, ginkgo and hawthorne are clinically not relevant, although in vitro
      studies point to drug interactions in vivo. Since for herbal extracts a positive
      in vitro - in vivo correlation regarding the impact on drug bioavailability is
      rare, results from in vitro studies should be carefully interpreted.

PMID- 21170701
TI  - Attenuation of chromium toxicity by bioremediation technology.
AB  - Chromium is an important toxic environmental pollutant. Chromium pollution
      results largely from industrial activities, but other natural and anthropogenic
      sources also contribute to the problem. Plants that are exposed to environmental
      contamination by chromium are affected in diverse ways, including a tendency to
      suffer metabolic stress. The stress imposed by Cr exposure also extends to
      oxidative metabolic stress in plants that leads to the generation of active toxic
      oxygen free radicals. Such active free radicals degrade essential biomolecules
      and distort plant biological membranes. In this chapter, we describe sources of
      environmental chromium contamination, and provide information about the toxic
      impact of chromium on plant growth and metabolism. In addition, we address
      different phytoremediation processes that are being studied for use worldwide, in
      contaminated regions, to address and mitigate Cr pollution. There has been a long
      history of attempts to successfully mitigate the toxic effects of chromium
      contaminated soil on plants and other organisms. One common approach, the
      shifting of polluted soil to landfills, is expensive and imposes environmental
      risks and health hazards of its own. Therefore, alternative eco-friendly
      bioremediation approaches are much in demand for cleaning chromium-polluted
      areas. To achieve its cleaning effects, bioremediation utilizes living organisms
      (bacteria, algae, fungi, and plants) that are capable of absorbing and processing
      chromium residues in ways which amend or eliminate it. Phytoremediation
      (bioremediation with plants) techniques are increasingly being used to reduce
      heavy metal contamination and to minimize the hazards of heavy metal toxicity. To
      achieve this, several processes, viz., rhizofiltration, phytoextraction,
      phytodetoxification, phytostabilization, and phytovolatilization, have been
      developed and are showing utility in practice, or promise. Sources of new native
      hyperaccumulator plants for use at contaminated sites are needed and constitute a
      key goal of ongoing phytoremediation research programs. Such new plants are
      needed to enhance the attractiveness of phytoremediation as an effective,
      affordable, and eco-friendly technique to achieve successful clean-up of metal
      contaminated sites worldwide.

PMID- 21170702
TI  - The effects of radionuclides on animal behavior.
AB  - Concomitant with the expansion of the nuclear industry, the concentrations of
      several pollutants, radioactive or otherwise, including uranium, caesium, cadmium
      and cobalt, have increased over the last few decades. These elemental pollutants
      do exist in the environment and are a threat to many organisms. Behavior
      represents the integration of all the anatomical adaptations and physiological
      processes that occur within an organism. Compared to other biological endpoints,
      the effects of pollutants on animal behavior have been the focus of only a few
      studies. However, behavioral changes appear to be ideal for assessing the effects
      of pollutants on animal populations, because behavior links physiological
      functions with ecological processes. The alteration of behavioral responses can
      have severe implications for survival of individuals and of population of some
      species. Behavioral disruptions may derive from several underlying mechanisms:
      disruption of neuro-sensorial activity and of endocrines, or oxidative and
      metabolic disruptions. In this review, we presented an overview of the current
      literature in which the effects of radioactive pollutants on behavior in humans,
      rodents, fish and wildlife species are addressed. When possible, we have also
      indicated the potential underlying mechanisms of the behavioral alterations and
      parameters measured. In fried, chronic uranium contamination is associated with
      behavior alterations and mental disorders in humans, and cognitive deficits in
      rats. Comparative studies on depleted and enriched uranium effects in rats showed
      that chemical and radiological activities of this metal induced negative effects
      on several behavioral parameters and also produced brain oxidative stress.
      Uranium exposure also modifies feeding behavior of bivalves and reproductive
      behavior of fish. Studies of the effects of the Chernobyl accident shows that
      chronic irradiation to 137Cs induces both nervous system diseases and mental
      disorders in humans leading to increased suicides, as well as modification of
      preferred nesting sites, reduced hatching success and fecundity in birds that
      live in the Chernobyl zone. No significant effect from caesium exposure was shown
      in laboratory experiments with rats, but few studies were conducted. Data on
      radioactive cadmium are not available in the literature, but the effects of its
      metallic form have been well studied. Cadmium induces mental retardation and
      psychomotor alterations in exposed populations and increases anxiety in rats,
      leading to depression. Cadmium exposure also results in well-documented effects
      on feeding and burrowing behavior in several invertebrate species (crustaceans,
      gastropods, annelids, bivalves) and on different kinds of fish behavior (swimming
      activity, fast-start response, antipredatory behavior). Cobalt induces memory
      deficits in humans and may be involved in Alzheimer's disease; gamma irradiation
      by cobalt also decreases fecundity and alters mating behavior in insects.
      Collectively, data are lacking or are meagre on radionuclide pollutants, and a
      better knowledge of their actions on the cellular and molecular mechanisms that
      control animal behavior is needed.

PMID- 21170703
TI  - Illicit drugs: contaminants in the environment and utility in forensic
      epidemiology.
AB  - The published literature that addresses the many facets of pharmaceutical
      ingredients as environmental contaminants has grown exponentially since the
      1990s. Although there are several thousand active ingredients used in medical
      pharmaceuticals worldwide, illicit drug ingredients (IDIs) have generally been
      excluded from consideration. Medicinal and illicit drugs have been treated
      separately in environmental research even though they pose many of the same
      concerns regarding the potential for both human and ecological exposure. The
      overview presented here covers the state of knowledge up until mid-2010 regarding
      the origin, occurrence, fate, and potential for biological effects of IDIs in the
      environment. Similarities exist with medical pharmaceuticals, particularly with
      regard to the basic processes by which these ingredients enter the environment-
      excretion of unmetabolized residues (including via sweat), bathing, disposal, and
      manufacturing. The features of illicit drugs that distinguish them from medical
      pharmaceuticals are discussed. Demarcations between the two are not always clear,
      and a certain degree of overlap adds additional confusion as to what exactly
      defines an illicit drug; indeed, medical pharmaceuticals diverted from the legal
      market or used for non-medicinal purposes ar also captured in discussions of
      illicit drugs. Also needing consideration as par tof the universe of IDIs are the
      numerous adulterants and synthesis impurities often encountered in these very
      impure preparations. many of these extraneous chemicals have high biological
      activity themselves. In contract to medical pharmaceuticals, comparatively little
      is know about the fate and effects of IDIs in the environment. Environmental
      surveys for IDIs have revealed their presence in sewage wastewaters, raw sewage
      sludge and processed sludge (biosolids), and drinking water. Nearly nothing is
      known, however, regarding wildlife exposure to IDIs, especially aquatic exposure
      such as indicated by bioconcentration i tissues. In contrast to pharmaceuticals,
      chemical monitoring surveys have revealed the presence of certain IDIs in air and
      monetary currencies--the latter being of interest for the forensic tracking of
      money used in drug trafficking. Another unknown with regard to IDIs is the
      accuracy of current knowledge regarding the complete scope of chemical identities
      of the numerous types of IDIs in actual use (particularly some of the continually
      evolving designer drugs new to forensic chemistry) as well as the total
      quantities being trafficked, consumed, or disposed. The major aspect unique to
      the study of IDI's in the environment is making use of their presence in the
      environment as a tool to obtain better estimates of the collective usage of
      illicit drugs across entire communities. First proposed in 2001, but under
      investigation with field applications only since 2005, this new modeling approach
      for estimating drug usage by monitoring the concentrations of IDIs (or certain
      unique metabolites) in untreated sewage has potential as an additional source of
      data to augment or corroborate the information-collection ability of conventional
      written and oral surveys of drug-user populations. This still evolving monitoring
      tool has been called "sewer epidemiology" but is referred to in this chapter by a
      more descriptive proposed term "FEUDS" (Forensic Epidemiology Using Drugs in
      Sewage). The major limitation of FEUDS surrounds the variables involved at
      various steps performed in FEUDS calculations. These variables are summarized and
      span sampling and chemical analysis to the final numeric calculations, which
      particularly require a better understanding of IDI pharmacokinetics than
      currently exists. Although little examined in the literature, the potential for
      abuse of FEUDS as a tool in law enforcement is briefly discussed. Finally, the
      growing interest in FEUDS as a methodological approach for estimating collective
      public usage of illicit drugs points to the feasibility of mining other types of
      chemical information from sewage. On the horizon is the potential for "sewage
      information mining" (SIM) as a general approach for measuring a nearly limitless
      array of biochemical markers that could serve as collective indicators of the
      specific or general status of public health or disease at the community-wide
      level. SIM may create the opportunity to view communities from a new perspective-
      "communities as the patient." This could potentially lead to the paradigm of
      combining human and ecological communities as a single patient--as an
      interconnected whole.

PMID- 21170704
TI  - Seasonal variation in physicochemical parameters and heavy metals in water of
      Upper Lake of Bhopal.
AB  - Heavy metal pollution of fresh water is the single most important environmental
      threat to the future. Upper Lake is a freshwater lake, which is the major source
      of drinking water in the city of Bhopal, the capital city of M.P., the central
      province of India, but due to anthropogenic activities this lake is being
      polluted. During the investigation heavy metals and physicochemical parameters
      were analyzed to determine the water quality seasonally in the year of 2006 and
      2007. All the physicochemical parameters except DO (6.50-6.97 mg l-1), Free CO2
      (0.8-1.6 mg l-1) and BOD (5.47-6.85 mg l-1) were below the prescribed limit as
      recommended by Bureau of Indian Standards (BIS) for drinking water standards. In
      case of heavy metals, Ni (0.173-0.253 mg l-1) and Cr (0.047-0.087 mg l-1) were
      found beyond the prescribed limits (0.02 and 0.05 mg l-1, respectively), whereas
      Pb (0.057-0.087 mg l-1), Cu (0.016-0.020 mg l-1) and Hg (0.0006-0.0011 mg l-1)
      were within the safe limit. This study reveals that water of upper lake is
      partially polluted with heavy metals. It is recommended that strict vigilance and
      constant monitoring are needed to maintain water quality of the lake, which is a
      major source of potable water for the Bhopal city.

PMID- 21170705
TI  - Nickel: an overview of uptake, essentiality and toxicity in plants.
AB  - Nickel even though recognized as a trace element, its metabolism is very decisive
      for certain enzyme activities, maintaining proper cellular redox state and
      various other biochemical, physiological and growth responses. Study of the
      aspects related with uptake, transport and distributive localization of Ni is
      very important in various cellular metabolic processes particularly under
      increased nitrogen metabolism. This review article, in core, encompasses the dual
      behavior of Ni in plants emphasizing its systemic partitioning, essentiality and
      ill effects. However, the core mechanism of molecules involved and the successive
      physiological conditions required starting from the soil absorption,
      neutralization and toxicity generated is still elusive, and varies among the
      plants.

PMID- 21170706
TI  - Velocity storage in the human vertical rotational vestibulo-ocular reflex.
AB  - Human horizontal rotational vestibulo-ocular reflex (rVOR) has been extensively
      investigated: the horizontal semicircular canals sense yaw rotations with high
      pass filter dynamics and a time constant (TC) around 5 s, yet the rVOR response
      shows a longer TC due to a central processing stage, known as velocity storage
      mechanism (VSM). It is generally assumed that the vertical rVOR behaves similarly
      to the horizontal one; however, VSM processing of the human vertical rVOR is
      still to be proven. We investigated the vertical rVOR in eight healthy human
      subjects using three experimental paradigms: (1) per- and post-rotatory around an
      earth-vertical axis (ear down rotations, EDR), (2) post-rotatory around an earth
      horizontal axis with different stopping positions (static otolith stimulation),
      (3) per-rotatory around an earth-horizontal axis (dynamic otolith stimulation).
      We found that the TC of vertical rVOR responses ranged 3-10 s, depending both on
      gravity and on the direction of rotation. The shortest TC were found in response
      to post-rotatory earth-horizontal stimulation averaging 3.6 s, while they were
      prolonged in EDR stimulation, i.e. when the head angular velocity vector is
      aligned with gravity, with a mean value of about 6.0 s. Overall, the longest TC
      were observed in per-rotatory earth-horizontal stimulation, averaging 7.8 s. The
      finding of longer TC in EDR than in post-rotatory earth-horizontal stimulation
      indicates a role for the VSM in the vertical rVOR, although its contribution
      appears to be weaker than on the horizontal rVOR and may be directionally
      asymmetric. The results from per-rotatory earth-horizontal stimulation, instead,
      imply a role for the otoliths in controlling the duration of the vertical rVOR
      response. We found no reorientation of the response toward earth horizontal,
      indicating a difference between human and monkey rVOR.

PMID- 21170707
TI  - Unconstrained three-dimensional reaching in rhesus monkeys.
AB  - To better understand normative behavior for quantitative evaluation of motor
      recovery after injury, we studied arm movements by non-injured rhesus monkeys
      during a food-retrieval task. While seated, monkeys reached, grasped, and
      retrieved food items. We recorded three-dimensional kinematics and muscle
      activity, and used inverse dynamics to calculate joint moments due to gravity,
      segmental interactions, and to the muscles and tissues of the arm. Endpoint paths
      showed curvature in three dimensions, suggesting that maintaining straight paths
      was not an important constraint. Joint moments were dominated by gravity.
      Generalized muscle and interaction moments were less than half of the
      gravitational moments. The relationships between shoulder and elbow resultant
      moments were linear during both reach and retrieval. Although both reach and
      retrieval required elbow flexor moments, an elbow extensor (triceps brachii) was
      active during both phases. Antagonistic muscles of both the elbow and hand were
      co-activated during reach and retrieval. Joint behavior could be described by
      lumped-parameter models analogous to torsional springs at the joints. Minor
      alterations to joint quasi-stiffness properties, aided by interaction moments,
      result in reciprocal movements that evolve under the influence of gravity. The
      strategies identified in monkeys to reach, grasp, and retrieve items will allow
      the quantification of prehension during recovery after a spinal cord injury and
      the effectiveness of therapeutic interventions.

PMID- 21170708
TI  - Non-invasive brain stimulation enhances fine motor control of the hemiparetic
      ankle: implications for rehabilitation.
AB  - We set out to answer two questions with this study: 1. Can stroke patients
      improve voluntary control of their paretic ankle by practising a visuo-motor
      ankle-tracking task? 2. Are practice effects enhanced with non-invasive brain
      stimulation? A carefully selected sample of chronic stroke patients able to
      perform the experimental task attended three data collection sessions.
      Facilitatory transcranial direct current stimulation (tDCS) was applied in a
      random order over the lower limb primary motor cortex of the lesioned hemisphere
      or the non-lesioned hemisphere or sham stimulation was delivered over the
      lesioned hemisphere. In each session, tDCS was applied as patients practiced
      tracking a sinusoidal waveform for 15 min using dorsiflexion-plantarflexion
      movements of their paretic ankle. The difference in tracking error prior to, and
      after, the 15 min of practice was calculated. A practice effect was revealed
      following sham stimulation, and this effect was enhanced with tDCS applied over
      the lesioned hemisphere. The practice effect observed following sham stimulation
      was eliminated by tDCS applied over the non-lesioned hemisphere. The study
      provides the first evidence that non-invasive brain stimulation applied to the
      lesioned motor cortex of moderate- to well-recovered stroke patients enhances
      voluntary control of the paretic ankle. The results provide a basis for examining
      whether this enhanced ankle control can be induced in patients with greater
      impairments and whether enhanced control of a single or multiple lower limb
      joints improves hemiparetic gait patterns.

PMID- 21170709
TI  - Does anastrozole affect bone resorption similarly in early and late
      postmenopausal women?
AB  - The aim of this study was to determine whether the bone-resorption response to
      anastrozole differed according to initial patient age in postmenopausal women
      with breast cancer in a cross-sectional study. Second-morning void urines were
      collected for measurement of urinary cross-linked N-telopeptide of type I
      collagen (uNTx, corrected for creatinine and log-transformed) from postmenopausal
      women, 99 with breast cancer on anastrozole (ABC), 88 with newly diagnosed breast
      cancer (NDBC), and 137 community-dwelling healthy control (HC) women. Bone
      mineral density (BMD) was also measured at the lumbar spine (LS, L2-L4) and the
      femoral neck (FN) in the ABC group. uNTx (nanomole bone collagen
      equivalents/millimole creatinine) levels increased with age in HC subjects. In
      patients <70 years, anastrozole treatment led to a significant increase in uNTx
      compared with age-related HC subjects (1.74 vs. 1.55, P < 0.005). Patients >70
      years showed no such increase compared to HC (1.72 vs. 1.69, nonsignificant);
      however, NDBC women >70 years had uNTx levels significantly lower than HC women
      (1.59 vs. 1.69, P < 0.05). There was no difference in uNTx levels above and below
      the age of 70 years in NDBC women (1.56 vs. 1.59, nonsignificant). ABC women were
      more likely to have a positive LS BMD z score than age-matched controls.
      Anastrozole treatment increases bone turnover more in younger postmenopausal
      women with breast cancer than in older women compared to healthy controls. Higher
      LS BMD in ABC patients may help protect against fracture.

PMID- 21170710
TI  - Assessing ecological water quality with macroinvertebrates and fish: a case study
      from a small Mediterranean river.
AB  - Biological elements, such as benthic macroinvertebrates and fish, have been used
      in assessing the ecological quality of rivers according to the requirements of
      the Water Framework Directive. However, the concurrent use of multiple organism
      groups provides a broader perspective for such evaluations, since each biological
      element may respond differently to certain environmental variables. In the
      present study, we assessed the ecological quality of a Greek river (RM4 type),
      during autumn 2003 and spring 2004 at 10 sites, with benthic macroinvertebrates
      and fish. Hydromorphological and physicochemical parameters, habitat structure,
      and riparian vegetation were also considered. Pollution sensitive
      macroinvertebrate taxa were more abundant at headwaters, which had good/excellent
      water quality according to the Hellenic Evaluation System (HES). The main river
      reaches possessed moderate water quality, while downstream sites were mainly
      characterised as having bad or poor water quality, dominated by pollution
      tolerant macroinvertebrate taxa. Macroinvertebrates related strongly to local
      stressors as chemical degradation (ordination analysis CCA) and riparian quality
      impairment (bivariate analysis) while fish did not. Fish were absent from the
      severely impacted lower river reaches. Furthermore, external pathological signs
      were observed in fish caught at certain sites. A combined use of both
      macroinvertebrates and fish in biomonitoring programs is proposed for providing a
      safer assessment of local and regional habitat impairment.

PMID- 21170711
TI  - Antifungal activity of PvD1 defensin involves plasma membrane permeabilization,
      inhibition of medium acidification, and induction of ROS in fungi cells.
AB  - In recent years, studies have demonstrated the function of many antimicrobial
      peptides against an extensive number of microorganisms that have been isolated
      from different plant species and that have been used as models for the study of
      various cellular processes linked to these peptides' activities. Recently, a new
      defensin from Phaseolus vulgaris (L.) seeds, named PvD(1,) was isolated and
      characterized. PvD(1) was purified through anion exchange and phase-reverse
      chromatography. PvD(1)'s antifungal activity was tested. A SYTOX Green uptake
      assay revealed that the defensin PvD(1) is capable of causing membrane
      permeabilization in the filamentous fungi Fusarium oxysporum, Fusarium solani,
      and Fusarium laterithium and in yeast strains Candida parapsilosis, Pichia
      membranifaciens, Candida tropicalis, Candida albicans, Kluyveromyces marxiannus,
      and Saccharomyces cerevisiae at a concentration of 100 MUg/ml. Ultrastructural
      analysis of C. albicans and C. guilliermondii cells treated with this defensin
      revealed disorganization of both cytoplasmic content and the plasma membrane.
      PvD(1) is also able to inhibit glucose-stimulated acidification of the medium by
      yeast cells and filamentous fungi, as well as to induce the production of
      reactive oxygen species and nitric oxide in C. albicans and F. oxysporum cells.

PMID- 21170712
TI  - Microarray analysis of the chelerythrine-induced transcriptome of Mycobacterium
      tuberculosis.
AB  - Chelerythrine (a natural quaternary benzophenanthridine alkaloid) is an extract
      from the roots of Chelidonium majus with potential antimycobacterial activity. To
      reveal the possible mechanism of action of chelerythrine against Mycobacterium
      tuberculosis (M. tuberculosis), commercial oligonucleotide microarrays were used
      to analyze the genome-wide transcriptional changes triggered by treatment with
      subinhibitory concentrations of chelerythrine. Quantitative real-time RT-PCR was
      performed for selected genes to verify the microarray results. We interpreted our
      microarray data using Agilent software. Analysis of the microarray data revealed
      that a total of 759 genes were differentially regulated by chelerythrine. Of
      these, 372 genes were upregulated, and 387 genes were downregulated. Some of the
      important genes that were significantly regulated are related to different
      pathways (such as urease), methoxy-mycolic acid synthase, surface-exposed lipids,
      the heat shock response, and protein synthesis. This genome-wide transcriptomics
      approach produced the first insights into the response of M. tuberculosis to a
      chelerythrine challenge.

PMID- 21170713
TI  - Enhancer-promoter interference and its prevention in transgenic plants.
AB  - Biotechnology has several advantages over conventional breeding for the precise
      engineering of gene function and provides a powerful tool for the genetic
      improvement of agronomically important traits in crops. In particular, it has
      been exploited for the improvement of multiple traits through the simultaneous
      introduction or stacking of several genes driven by distinct tissue-specific
      promoters. Since transcriptional enhancer elements have been shown to override
      the specificity of nearby promoters in a position- and orientation-independent
      manner, the co-existence of multiple enhancers/promoters within a single
      transgenic construct could be problematic as it has the potential to cause the
      mis-expression of transgene product(s). In order to develop strategies with,
      which to prevent such interference, a clear understanding of the mechanisms
      underlying enhancer-mediated activation of target promoters, as well as the
      identification of DNA sequences that function to block these interactions in
      plants, will be necessary. To date, little is known concerning enhancer function
      in plants and only a very limited number of enhancer-blocking insulators that
      operate in plant species have been identified. In this review, we discuss the
      current knowledge surrounding enhancer-promoter interactions, as well as possible
      means of minimizing such interference during plant transformation experiments.

PMID- 21170714
TI  - Production of reactive oxygen species and induction of signaling pathways for the
      ACO gene expressions in tomato plants triggered by the volatile organic compound
      ether.
AB  - Diethyl ether (ether), a volatile organic compound, is widely used as an
      industrial solvent and easily released to the environment. Acute exposure of
      tomato plants to high concentrations of ether caused young leaves to curl.
      Histochemical analyses revealed that superoxide anion (*O(2-) and hydrogen
      peroxide were formed sequentially by ether, and that (*O(2-) was the major ROS
      produced in response to ether exposure. We observed cell death by microscopic
      inspection of Evans blue-stained samples, following fumigation with ether for 6
      h. The ethylene biosynthetic gene, 1-aminocyclopropane-1-carboxylic acid oxidase
      (ACO), was induced as early as 15-30 min after ether fumigation and could be
      activated at ether concentration as low as 1 MUL/L. Induction of ACO gene
      expression occurred simultaneously with ROS accumulation and coincided with the
      occurrence of cell death. Simultaneous treatment of tomato plants with mechanical
      wounding and ether induced differential expression of the ACO gene family. Ether
      strongly induced ACO4 and moderately induced ACO1, whereas mechanical wounding
      strongly induced ACO1 and slightly induced ACO4. Induction of the ACO gene family
      by ether occurred via different signaling pathways. While the ACO1 gene was
      induced via protein phosphorylation, the ACO4 gene was induced through protein
      dephosphorylation. Induction of ACO1 and ACO4 might be through MPK1, MPK2, MPK3,
      and PP2Ac1. These results suggest that the cellular responses of tomato plants to
      ether are different from the plant responses to ozone, and that tomato plants
      respond to different air pollutants through different perceptions and downstream
      signaling pathways.

PMID- 21170716
TI  - Aneuploidy among androgenic progeny of hexaploid triticale (XTriticosecale
      Wittmack).
AB  - Doubled haploids are an established tool in plant breeding and research. Of
      several methods for their production, androgenesis is technically simple and can
      efficiently produce substantial numbers of lines. It is well suited to such crops
      as hexaploid triticale. Owing to meiotic irregularities of triticale hybrids,
      aneuploidy may affect the efficiency of androgenesis more severely than in
      meiotically stable crops. This study addresses the issue of aneuploidy among
      androgenic regenerants of triticale. Plant morphology, seed set and seed quality
      were better predictors of aneuploidy, as determined cytologically, than flow
      cytometry. Most aneuploids were hypoploids and these included nullisomics,
      telosomics, and translocation lines; among 42 chromosome plants were nulli
      tetrasomics. Rye chromosomes involved in aneuploidy greatly outnumbered wheat
      chromosomes; in C(0) rye chromosomes 2R and 5R were most frequently involved.
      While the frequency of nullisomy 2R was fairly constant in most cross
      combinations, nullisomy 5R was more frequent in the most recalcitrant
      combination, and its frequency increased with time spent in culture with up to
      70% of green plants recovered late being nullisomic 5R. Given that 5R was not
      involved in meiotic aberrations with an above-average frequency, it is possible
      that its absence promotes androgenesis or green plant regeneration. Overall,
      aneuploidy among tested combinations reduced the average efficiency of double
      haploid production by 35% and by 69% in one recalcitrant combination, seriously
      reducing the yield of useful lines.

PMID- 21170715
TI  - Genotoxic stress and DNA repair in plants: emerging functions and tools for
      improving crop productivity.
AB  - Crop productivity is strictly related to genome stability, an essential requisite
      for optimal plant growth/development. Genotoxic agents (e.g., chemical agents,
      radiations) can cause both chemical and structural damage to DNA. In some cases,
      they severely affect the integrity of plant genome by inducing base oxidation,
      which interferes with the basal processes of replication and transcription,
      eventually leading to cell death. The cell response to oxidative stress includes
      several DNA repair pathways, which are activated to remove the damaged bases and
      other lesions. Information concerning DNA repair in plants is still limited,
      although results from gene profiling and mutant analysis suggest possible
      differences in repair mechanisms between plants and other eukaryotes. The present
      review focuses on the base- and nucleotide excision repair (BER, NER) pathways,
      which operate according to the most common DNA repair rule (excision of damaged
      bases and replacement by the correct nucleotide), highlighting the most recent
      findings in plants. An update on DNA repair in organelles, chloroplasts and
      mitochondria is also provided. Finally, it is generally acknowledged that DNA
      repair plays a critical role during seed imbibition, preserving seed vigor.
      Despite this, only a limited number of studies, described here, dedicated to
      seeds are currently available.

PMID- 21170717
TI  - Spirituality and end-of-life care in disadvantaged men dying of prostate cancer.
AB  - PURPOSE: Despite the positive influence of spiritual coping on the acceptance of
      a cancer diagnosis, higher spirituality is associated with receipt of more high
      intensity care at the end of life. The purpose of our study was to assess the
      association between spirituality and type of end-of-life care received by
      disadvantaged men with prostate cancer. METHODS: We studied low-income, uninsured
      men in IMPACT, a state-funded public assistance program, who had died since its
      inception in 2001. Of the 60 men who died, we included the 35 who completed a
      spirituality questionnaire at program enrollment. We abstracted sociodemographic
      and clinical information as well as treatment within IMPACT, including zolendroic
      acid, chemotherapy, hospice use, and palliative radiation therapy. We measured
      spirituality with the Functional Assessment of Chronic Illness Therapy-Spiritual
      Well-Being questionnaire (FACIT-Sp) and compared end-of-life care received
      between subjects with low and high FACIT-Sp scores using chi-squared analyses.
      RESULTS: A higher proportion of men with high (33%) versus low (13%) spirituality
      scores enrolled in hospice, although our analysis was not adequately powered to
      demonstrate statistical significance. Likewise, we saw a trend toward increased
      receipt of palliative radiation among those with higher spirituality (37% vs.
      25%, P=0.69). The differences in end-of-life care received among those with low
      and high spirituality varied little by the FACIT-Sp peace and faith subscales.
      CONCLUSIONS: End-of-life care was similar between men with lower and higher
      spirituality. Men with higher spirituality trended toward greater hospice use,
      suggesting that they redirected the focus of their care from curative to
      palliative goals.

PMID- 21170718
TI  - Epigallocatechin-3-gallate (EGCG) downregulates EGF-induced MMP-9 in breast
      cancer cells: involvement of integrin receptor alpha5beta1 in the process.
AB  - PURPOSE: Epidermal growth factor receptor (EGFR/ErbB1) is a transmembrane protein
      with tyrosine kinase activity activated mainly by ligand, EGF. Matrix
      metalloproteinases (MMPs) are a family of proteinases that catalyses the
      destruction of ECM, among which MMP-9 has important role in tumor cell invasion.
      Secretion of MMP-9 is stimulated by a variety of factors, EGFR being significant.
      Epigallocatechin-3-gallate (EGCG) is a major polyphenol of green tea that
      inhibits cell proliferation and invasion. Here, we study the effect of EGFR alone
      and in collaboration with fibronectin on the status of MMP-9 in human breast
      cancer cell MDA-MB-231 and its molecular mechanism; study the role of EGCG on the
      induced MMP-9; and elucidate the signaling molecules involved in the process.
      METHODS: We performed zymography, immunoblots, real-time RT-PCR, cell adhesion
      assay, siRNA studies, and electrophoretic mobility shift assay to demonstrate the
      findings. RESULT: EGF induces MMP-9 activity and expression; FAK, PI3 K, and ERK
      are mainly involved in the process. EGF also causes the transactivation of MMP-9
      gene by increasing the DNA binding activity of the transcription factors. EGCG
      downregulates EGF-induced MMP-9 expression by inhibiting the involved regulatory
      kinases. EGF collaborates with fibronectin to create a synergistic response, and
      EGCG inhibits the synergistic response in MDA-MB-231. CONCLUSION: The study
      demonstrates the requirement of cross talk between cell matrix adhesion molecules
      and growth factor receptors to improve biological responses and shows FAK/ERK as
      the pivotal point of this convergence in human breast carcinoma cell line MDA-MB
      231. We also establish EGCG as the potential anti-tumor agent in human breast
      carcinoma.

PMID- 21170719
TI  - Non-neoplastic salivary gland lesions: a 15-year study.
AB  - The spectrum of salivary gland lesions is wide and the relative incidence of
      neoplastic versus non-neoplastic lesions is variable in different studies. A
      series of non-neoplastic salivary gland lesions is reviewed to analyze their
      spectrum and their relative frequency. This is a retrospective study of salivary
      gland excisions and biopsies received in our department from January 1994 to
      December 2008. Routine hematoxylin and eosin-stained sections of all the salivary
      gland excisions and biopsies received were analyzed. Of the 393 salivary gland
      excisions and biopsies received, 216 cases were reported as non-neoplastic (55%)
      and formed our study group; 177 (45%) were neoplastic. Non-neoplastic lesions
      were more frequent in major salivary glands (65.7%) and submandibular gland was
      the most commonly involved (66.2%). Lip was the most frequent site (81.7%) for
      minor salivary gland lesions. Inflammation was the predominant pathological
      finding (49.5%), of which non-specific chronic sialadenitis constituted the
      majority (86.9%). Sialolithiasis was present in 22 cases (20.6%); all of these
      cases were of non-specific chronic sialadenitis. Cysts were second in frequency
      (36.6%), of which mucocele was the most common (54.5%). There were 5.6% cases of
      benign lympho-epithelial lesions, while normal salivary gland tissue was seen in
      6.5% cases. Non-neoplastic salivary gland diseases are more common than
      neoplastic diseases and have a wide disease spectrum.

PMID- 21170720
TI  - Comparative outcomes of antireflux treatment for laryngopharyngeal reflux
      symptoms and upper abdominal symptoms in patients with endoscopic esophagitis.
AB  - The objectives of this prospective study are to determine the prevalence of
      laryngopharyngeal reflux (LPR) symptoms in patients with endoscopic esophagitis,
      to investigate the relationship between LPR symptoms and upper abdominal symptoms
      of gastroesophageal reflux disease (GERD) and to compare the treatment responses
      of both symptom groups. 120 consecutive patients having complaints of GERD were
      included. Group I consisted of 62 patients with a diagnosis of endoscopic
      esophagitis. The second group consisted of 58 subjects with no detectable
      pathology at gastroscopy. LPR symptoms and upper abdominal symptoms were graded.
      Proton pump inhibitors (PPI) were prescribed to patients. Both groups of symptoms
      were compared in two groups of patients. The improvement in symptoms was
      evaluated after treatment. The frequencies of LPR symptoms were statistically
      higher in patients with endoscopic esophagitis. All LPR symptoms were
      statistically relieved in their frequency after treatment. The decrease in LPR
      symptom scores after treatment in group I was statistically significant. FSSG
      (frequency scale for the symptoms of GERD) scores were statistically higher in
      group I than in group II before treatment. After treatment, FSSG scores were
      significantly decreased in group I. There was statistically significant positive
      correlation between the LPR symptom scores and FSSG scores before treatment. In
      conclusion, there is a high incidence of LPR symptoms and upper abdominal
      symptoms in patients with endoscopic esophagitis. LPR and upper abdominal
      symptoms responded well to antireflux treatment in patients with endoscopic
      esophagitis.

PMID- 21170721
TI  - A preliminary study on the role of inherited prothrombotic risk factors in
      Taiwanese patients with sudden sensorineural hearing loss.
AB  - Sudden sensorineural hearing loss (SSHL) is a disease with unknown etiology.
      Recently, several studies revealed that some inherited prothrombotic risk factors
      are associated with SSHL in western populations. The objective of this study was
      to investigate the roles of the two most common genetic prothrombotic factors,
      the factor V Leiden G1691A and prothrombin G20210A in Taiwanese patients with
      SSHL. Twenty-four patients diagnosed with SSHL of more than 30 dB on average pure
      tone audiometry (PTA) and thirty-six healthy subjects without a history of
      hearing loss were enrolled in this study. Genomic DNA was isolated from
      peripheral blood leukocytes and the single nucleotide polymorphisms (SNPs)
      genotyping of factor V Leiden G1691A and prothrombin G20210A were analyzed using
      the TaqMan genotyping assays. Neither factor V Leiden G1691A nor prothrombin
      G20210A was detected in SSHL patients or in the control subjects. Both the
      patient group and the control group exhibited wild-type V Leiden 1691GG and wild
      type prothrombin 20210GG. In conclusion, the factors V Leiden G1691A and
      prothrombin G20210A do not seem to play any role in Taiwanese patients with SSHL.
      Further studies with a large series of patients are needed to identify other
      possible candidate genes in order to elucidate the pathogenesis of SSHL.

PMID- 21170722
TI  - Hospitalization rates and survival associated with COPD: a nationwide Danish
      cohort study.
AB  - We examined rates of first hospitalization for COPD, rates of 5-year mortality
      among patients hospitalized for COPD, and comparisons of mortality between COPD
      patients and a matched cohort free of COPD. We computed standardized rates of
      first COPD hospitalization. Using Cox regression, we compared 180- and 181-day to
      5-year mortality among COPD patients with the comparison cohort. We used medical
      databases in Denmark (population 5.4 million) from 1997 to 2006. We included
      patients 40 years or older with first hospitalization for COPD (64,499) and an
      age- and gender-matched comparison cohort of persons without COPD hospitalization
      (322,495). We examined the incidence of COPD hospitalization and risks and rates
      of mortality in the 5 years after hospitalization. Standardized rates of first
      hospitalization for COPD declined from 276 per 100,000 person-years in 1999 to
      231 per 100,000 person-years in 2006. Within 180 days of hospitalization, 16% of
      COPD patients and 2.4% of persons in the matched cohort died (adjusted hazard
      ratio = 7.00, 95% CI = 6.79-7.22). Between 181 days and 5 years, 46% of COPD
      patients who survived the first 180 days and 19% of persons in the comparison
      cohort died (adjusted hazard ratio = 2.91, 95% CI = 2.86-2.95). COPD and comorbid
      diseases interacted to increase mortality in the first 180 days, but not
      thereafter. COPD continues to be a major public health problem causing
      substantial mortality in the 5 years after hospitalization, particularly in the
      first 180 days and in patients with comorbid diseases.

PMID- 21170723
TI  - Exploring the pathophysiology of mal de debarquement.

PMID- 21170724
TI  - Does age attenuate aerobic conditioning response in postmenopausal women?
      Response.

PMID- 21170725
TI  - Bioluminescence imaging of Arc expression enables detection of activity-dependent
      and plastic changes in the visual cortex of adult mice.
AB  - Induction of the activity-regulated cytoskeleton-associated protein gene (Arc),
      one of the immediate early genes, in the brain correlates with various sensory
      processes, natural behaviors, and pathological conditions. Arc is also involved
      in synaptic plasticity during development. Thus, in vivo monitoring of Arc
      expression is useful for the analysis of physiological and pathological
      conditions in the brain. Recently, in vivo imaging of Arc expression using
      various green fluorescent protein-based probes has been reported; however, these
      probes can only be applied for the detection of fluorescence signals from
      superficial layers of the cortex with some autofluorescence noise. Here, we
      generated a novel transgenic mouse strain to monitor the neuronal-activity
      dependent Arc expression using bioluminescence signals in vivo. Because of the
      very high sensitivity with a high signal-to-noise ratio, we detected neuronal
      activity-dependent plastic changes in the bioluminescence signal intensity in the
      mouse visual cortex after visual deprivation, suggesting structural plasticity
      after peripheral lesions in adults. We also detected drastic changes in
      bioluminescence signals after seizure induction with kainic acid. Our novel mouse
      strain will be valuable for the continuous monitoring of neuronal-activity
      dependent Arc expression in the brain under physiological and pathological
      conditions.

PMID- 21170726
TI  - Experiments and three phase modelling of a biofilter for the removal of toluene
      and trichloroethylene.
AB  - Volatile organic compounds, namely, toluene, trichloroethylene, styrene, etc.,
      disposed off by electronics and polymer industries, are very harmful. The
      treatment of VOC laden air through biochemical route is one of the potential
      options for reduction of their concentration in parts per million or parts per
      billion level. Under the present investigation, a 0.05-m diameter and 0.58-m high
      trickle bed biofilter has been studied for the removal of VOCs namely toluene and
      trichloroethylene from a simulated air-VOC mixture using pure strain of
      Pseudomonas putida (NCIM2650) in immobilized form. Inlet concentrations of VOCs
      have been varied in two ranges, the lower being 0.20-2.00 g/m(3) and higher being
      10-20 g/m(3), respectively. The Monod type rate kinetics of removal of VOCs has
      been determined. A three-phase deterministic mathematical model has been
      developed taking the simultaneous reaction kinetics and interphase (gas to liquid
      to biofilm) mass transfer rate of VOCs into consideration. Experimentally
      determined kinetic parameters and mass transfer coefficients calculated using
      standard correlations have been used. Concentrations have been simulated for all
      the three phases. Simulated results based on the model have been compared with
      the experimental ones for both gas and liquid phases satisfactorily. The
      mathematical model validated through the successful comparison with experimental
      data may be utilized for the prediction of performance of biofilters undergoing
      removal of different VOCs in any further investigation and may be utilized for
      the scale-up of the system to industrial scale.

PMID- 21170727
TI  - Description of a novel single mutation in the AcMNPV polyhedrin gene that results
      in abnormally large cubic polyhedra.
AB  - We describe a point mutation in the AcMNPV polyhedrin gene that produces
      abnormally large cubic polyhedra in packaging cell lines. A polyhedrin mutant
      baculovirus in which the single change E44G was introduced confirmed that this
      mutation and no other alterations in the AcMNPV genome was responsible for the
      abnormal phenotype. Although baculoviral VP39 protein was detected inside mutant
      polyhedra, electron microscopy demonstrated that only a proportion of the large
      crystals allow occlusion of virions. When compared with wild-type polyhedra, the
      mutant inoculum showed reduced oral infectivity for Rachiplusia nu larvae. Hence,
      the amino acid 44 substitution in the AcMNPV polyhedrin protein alters polyhedrin
      assembly and affects viral occlusion and infectivity.

PMID- 21170728
TI  - Presence of a polyA tail at the 3' end of maize rayado fino virus RNA.
AB  - Maize rayado fino virus (MRFV) is distinct from other marafiviruses in that its
      genome reportedly lacks a poly(A) tail at the 3' terminus. We now show that the
      MRFV genome is indeed polyadenylated.

PMID- 21170729
TI  - The genomes of four novel begomoviruses and a new Sida micrantha mosaic virus
      strain from Bolivian weeds.
AB  - Begomovirus is the largest genus within the family Geminiviridae and includes
      economically important plant DNA viruses infecting a broad range of plant species
      and causing devastating crop diseases, mainly in subtropical and tropical
      countries. Besides cultivated plants, many weeds act as virus reservoirs. Eight
      begomovirus isolates from Bolivian weeds were examined using rolling-circle
      amplification (RCA) and restriction fragment length polymorphism (RFLP). An
      efficient, novel cloning strategy using limited Sau3A digestion to obtain tandem
      repeat inserts allowed the sequencing of the complete genomes. The viruses were
      classified by phylogenetic analysis as typical bipartite New World begomoviruses.
      Four of them represented distinct new virus species, for which the names Solanum
      mosaic Bolivia virus, Sida mosaic Bolivia virus 1, Sida mosaic Bolivia virus 2,
      and Abutilon mosaic Bolivia virus are proposed. Three were variants of a new
      strain of Sida micrantha mosaic virus (SimMV), SimMV-rho[BoVi07], SimMV
      rho[Bo:CF1:07] and SimMV-rho[Bo:CF2:07], and one was a new variant of a
      previously described SimMV, SimMV-MGS2:07-Bo.

PMID- 21170730
TI  - Adjuvants and delivery systems in veterinary vaccinology: current state and
      future developments.
AB  - Modern adjuvants should induce strong and balanced immune responses, and it is
      often desirable to induce specific types of immunity. As an example, efficient
      Th1-immunity-inducing adjuvants are highly in demand. Such adjuvants promote good
      cell-mediated immunity against subunit vaccines that have low immunogenicity
      themselves. The development of such adjuvants may take advantage of the increased
      knowledge of the molecular mechanisms and factors controlling these responses.
      However, knowledge of such molecular details of immune mechanisms is relatively
      scarce for species other than humans and laboratory rodents, and in addition,
      there are special considerations pertaining to the use of adjuvants in veterinary
      animals, such as production and companion animals. With a focus on veterinary
      animals, this review highlights a number of approaches being pursued, including
      cytokines, CpG oligonucleotides, microparticles and liposomes.

PMID- 21170731
TI  - Towards a social discount rate for the economic evaluation of health technologies
      in Germany: an exploratory analysis.
AB  - Over the last decades, methods for the economic evaluation of health care
      technologies were increasingly used to inform reimbursement decisions. For a
      short time, the German Statutory Health Insurance makes use of these methods to
      support reimbursement decisions on patented drugs. In this context, the
      discounting procedure emerges as a critical component of these methods, as
      discount rates can strongly affect the resulting incremental cost-effectiveness
      ratios. The aim of this paper is to identify the appropriate value of a social
      discount rate to be used by the German Statutory Health Insurance for the
      economic evaluation of health technologies. On theoretical grounds, we build on
      the widespread view of contemporary economists that the social rate of time
      preference (SRTP) is the adequate social discount rate. For quantifying the SRTP,
      we first apply the market behaviour approach, which assumes that the SRTP is
      reflected in observable market interest rates. As a second approach, we derive
      the SRTP from optimal growth theory by using the Ramsey equation. A major part of
      the paper is devoted to specify the parameters of this equation. Depending on
      various assumptions, our empirical findings result in the range of 1.75-4.2% for
      the SRTP. A reasonable base case discount rate for Germany, thus, would be about
      3%. Furthermore, we deal with the much debated question whether a common discount
      rate for costs and health benefits or a lower rate for health should be applied
      in health economic evaluations. In the German social health insurance system, no
      exogenously fixed budget constraint does exist. When evaluating a new health
      technology, the health care decision maker is obliged to conduct an economic
      evaluation in order to examine whether there is an economically appropriate
      relation between the value of the health gains and the additional costs which are
      given by the value of the consumption losses due to the additional health care
      expenditures. Therefore, a discount rate lower than the SRTP for consumption
      should be applied if an increase in the consumption value of health is expected.
      However, given the limited empirical evidence on the relationship between
      consumption and the value of health, it is hardly possible to make reliable
      forecasts of this value. Regarding the practice of the German evaluation
      authority, it is not recommended to use differential discounting in the base
      case. Instead, the issue of differential discounting should be addressed in
      sensitivity analyses. Reducing the discount rate for health compared to the rate
      for costs by a figure in the range between near 0% and 3% may be considered to be
      appropriate for Germany.

PMID- 21170733
TI  - Power in the role of the medical director: what it is and how to get more.
AB  - The formal leadership of mental health care organizations commonly resides in an
      executive director, who may or may not have had clinical training. The medical
      director is a psychiatrist who reports to the executive director. For some, this
      arrangement suggests that the medical director lacks or has lost power in the
      organization. This paper examines more specifically the types of power available
      to the medical director using French & Raven (1959) and Raven (2008) bases of
      power framework. The executive director/medical director relationship can be
      thought of as a relationship between individuals holding formal and informal
      power, respectively. Although medical directors lack formal or positional power,
      they potentially have and can gain more informal power based on their recognized
      clinical/medical expertise, their personal presence and an assertive involvement
      and focus on the organizational mission.

PMID- 21170732
TI  - Fabrication of chitosan/poly(epsilon-caprolactone) composite hydrogels for tissue
      engineering applications.
AB  - The aim of this study was to fabricate three-dimensional (3D) porous
      chitosan/poly(epsilon-caprolactone) (PCL) hydrogels with improved mechanical
      properties for tissue engineering applications. A modified emulsion
      lyophilisation technique was developed to produce 3D chitosan/PCL hydrogels. The
      addition of 25 and 50 wt% of PCL into chitosan substantially enhanced the
      compressive strength of composite hydrogel 160 and 290%, respectively, compared
      to pure chitosan hydrogel. The result of ATR-FTIR imaging corroborated that PCL
      and chitosan were well mixed and physically co-existed in the composite
      structures. The composite hydrogels were constructed of homogenous structure with
      average pore size of 59.7 +/- 14 MUm and finer pores with average size of 4.4 +/-
      2 MUm on the wall of these larger pores. The SEM and confocal laser scanning
      microscopy images confirmed that fibroblast cells were attached and proliferated
      on the 3D structure of these composite hydrogels. The composite hydrogels
      acquired in this study possessed homogeneous porous structure with improved
      mechanical strength and integrity. They may have a high potential for the
      production of 3D hydrogels for tissue engineering applications.

PMID- 21170734
TI  - Serum biochemical characteristics of Beluga, Huso huso (L.), in response to blood
      sampling after clove powder solution exposure.
AB  - In order to investigate the effect of anesthesia on serum parameters, Beluga,
      Huso huso (L.) were blood-sampled immediately without anesthesia (control) or
      subjected to following anesthesia procedure: 40, 120, and 240 s exposure to
      3,000, 700, and 500 mg l-1 clove solution, respectively. Blood samples were
      collected after these periods, when fish were immobile and reached stage 4
      anesthesia. Results showed that cortisol and glucose levels were significantly
      high in 700 and 500 but not 3,000 mg l-1 group compared to control. Serum lactate
      levels were significantly high in 500 mg l-1 group compared to control group.
      Lactate levels were not significantly differed between control, 3,000, and 700 mg
      l-1 groups. There were no significant differences in serum levels of cholesterol,
      total protein, lactate dehydrogenase, aspartate aminotransferase, alanine
      aminotransferase, Na+, Cl-, K+, and Ca2+. Results suggest that rapid anesthesia
      with higher dose is better than slow anesthesia with lower dose for blood
      sampling in Beluga.

PMID- 21170735
TI  - Neurofibromin and amyloid precursor protein expression in dopamine D3 receptor
      knock-out mice brains.
AB  - Recently, it has been proposed that neurofibromin (NF1) forms a binding complex
      with amyloid precursor protein (APP) that interacts with the dopamine D(3)
      receptor (D(3)R). In the present study we investigated whether the absence of the
      D(3)R is correlated to modifications in the expression of both NF1 and APP.
      Quantitative real-time PCR analyses of both transcripts showed that NF1 mRNA
      levels were significantly reduced whereas APP levels were strikingly increased in
      D(3)R knock-out (D(3)R KO) as compared to wild type (WT) mice brains. Western
      blot analyses using mice whole brains produced comparable results with those
      obtained by mRNA measurements. Moreover, immunohistochemical analyses revealed a
      similar brain regional distribution of APP protein in the hippocampus, in the
      cerebral and cerebellar cortex of D(3)R KO mice. Conversely, hippocampal NF1
      immunoreactivity did not seem to be affected by the absence of D(3)Rs. Further
      analyses confirmed that regional NF1 protein expression in the hippocampus was
      not affected by the absence of the D(3)R, whereas APP levels were still increased
      in this specific brain region. In conclusion, these results show the existence of
      a correlation among the D(3)R, NF1 and APP in mice brains and thus show the
      regional-specific regulation of NF1 in brains of D(3)R KO, which may contribute
      to gain insights into the comprehension of novel underlying mechanisms that
      regulate brain function.

PMID- 21170736
TI  - Expression and distribution of dopamine transporter in cardiac tissues of the
      guinea pig.
AB  - Dopamine transporter (DAT) is a membrane protein that it is a marker for
      dopaminergic neurons. In the present work, throught Western blot and
      autoradiographic studies with a selective ligand for DAT ([(3)H] WIN-35428) and
      noradrenaline transporter (NET) ([(3)H] Nisoxetine), we search the expression and
      distribution of DAT in comparison with NET, in cardiac tissue of guinea pig in
      order to support the presence of dopaminergic nerve cells into the heart.
      Expression of DAT, and NET were evidenced by a bands of 75 and 54 kDa,
      respectively in the heart. Binding for DAT and NET were found in the four cardiac
      chambers. However, DAT show heterogeneous distribution with binding in right
      atria and in both ventricles, whereas NET show homogenous distribution in the
      four cardiac chambers. The results show the expression of DAT in cardiac tissues
      with a different distribution compared with NET, being an evidence for the
      presence of dopaminergic nerve cells into the heart.

PMID- 21170737
TI  - How family factors impact psychosocial functioning for African American consumers
      with schizophrenia.
AB  - There is a critical need to test how family contextual factors impact outpatient
      consumer functioning in schizophrenia. This is the first study of two companion
      studies reported here that tests family factors' influence on consumer
      functioning. Ninety-three low income inner-city African American consumer-family
      dyads were tested to see the possible impact of family factors, based on the EE
      and family caregiver burden literatures, on consumer psychosocial functioning
      (work, social, and independent living). The results supported a model wherein
      greater amounts of family contact had a significant relationship with better
      consumer psychosocial functioning. Additionally, family dysfunction had a direct
      negative relationship to consumer psychosocial functioning while family pressures
      and resources had an indirect negative relationship to consumer psychosocial
      functioning. Results are in marked contrast to what impacted consumer clinical
      functioning for the same sample. The findings appear to confirm that family
      factors differently impact the domains of clinical and psychosocial functioning.
      These findings are new for understanding the contextual factors that impact
      consumer functioning, especially psychosocial functioning.

PMID- 21170738
TI  - Antifungal susceptibility of bloodstream Candida isolates in Sfax hospital:
      Tunisia.
AB  - Invasive candidiasis has emerged as an important nosocomial infection, causing
      significant morbidity and mortality especially among critically ill patients. The
      aim of our study was to determine specie distribution and resistance profiles of
      Candida species isolated from blood cultures. MATERIALS AND METHODS: We conducted
      a retrospective study of all episodes of candidemia diagnosed in our laboratory
      from January 2006 to May 2009. The susceptibility to antifungal agents of all
      Candida isolates was tested by using a Sensititre((r)) YeastOne panel. RESULTS: A
      total of 130 Candida isolates were recovered from blood cultures. Candida
      tropicalis was the most frequent specie (37.7%), followed by C. albicans (22.3%),
      C. glabrata (19.2%), and C. parapsilosis (12.2%). All the isolates were inhibited
      by <=1 MUg/ml of amphotericin B and <=2 MUg/ml of caspofungin. For fluconazole,
      7.3% of clinical isolates were resistant. It was most active against C.
      parapsilosis (100% susceptible), C. albicans (95.8% susceptible), and C.
      tropicalis (94% susceptible). All of the fluconazole-susceptible isolates were
      susceptible to voriconazole, as were 83.3% of the fluconazole-susceptible-dose
      dependent isolates. Among fluconazole-resistant isolates, 85.7% were susceptible
      to voriconazole. CONCLUSIONS: In our institution, C. tropicalis was the most
      frequent specie isolated from the bloodstream. Caspofungin had an excellent in
      vitro activity against Candida isolates and was the drug of choice among
      fluconazole-resistant isolates.

PMID- 21170739
TI  - Impaired pulmonary immunity post-bone marrow transplant.
AB  - Infectious complications are a serious cause of morbidity and mortality following
      hematopoietic stem cell transplantation (HSCT), and the lung is a particular
      target organ post-transplant. Our laboratory has used a murine bone marrow
      transplant model to study alterations in immunity that occur as a result of
      transplantation. Our studies focus on immune responses that occur following
      immune cell reconstitution in the absence of immunosuppressive drug therapy or
      graft-versus-host disease. We have found that impaired clearance of both
      bacterial and viral pulmonary infections is related to specific alterations in
      immune cell function and cytokine production. Our data offer insight into
      mechanisms that contribute to opportunistic infections in HSCT recipients.

PMID- 21170741
TI  - CD8(+)T-cell-mediated control of HIV-1 and SIV infection.
AB  - A detailed understanding of the cellular response to human immunodeficiency virus
      (HIV-1) infection is needed to inform prevention and therapeutic strategies that
      aim to contain the AIDS pandemic. The cellular immune response plays a critical
      role in reducing viral load in HIV-1 infection and in the nonhuman primate model
      of SIV infection. Much of this virus suppressive activity has been ascribed to
      CD8(+)T-cell-directed cytolysis of infected CD4(+)T cells. However, emerging
      evidence suggests that CD8(+)T cells can maintain a lowered viral burden through
      multiple mechanisms. A thorough understanding of the CD8(+)T-cell functions in
      HIV-1 infection that correlate with viral control, the populations responsible
      for these functions, and the elicitation and maintenance of these responses can
      provide guidance for vaccine design and potentially the development of new
      classes of antiretroviral therapies. In this review, we discuss the CD8(+)T-cell
      correlates of protection in HIV-1 and SIV infection and recent advances in this
      field.

PMID- 21170740
TI  - Role of Ras/Raf/MEK/ERK signaling in physiological hematopoiesis and leukemia
      development.
AB  - Recent research on hematological malignancies has shown that malignant cells
      often co-opt physiological pathways to promote their growth and development. Bone
      marrow homeostasis requires a fine balance between cellular differentiation and
      self-renewal; cell survival and apoptosis; and cellular proliferation and
      senescence. The Ras/Raf/MEK/ERK pathway has been shown to be important in
      regulating these biological functions. Moreover, the Ras/Raf/MEK/ERK pathway has
      been estimated to be mutated in 30% of all cancers, thus making it the focus of
      many scientific studies which have lead to a deeper understanding of cancer
      development and help to elucidate potential weaknesses that can be targeted by
      pharmacological agents [1]. In this review, we specifically focus on the role of
      this pathway in physiological hematopoiesis and how augmentation of the pathway
      may lead to hematopoietic malignancies. We also discuss the challenges and
      success of targeting this pathway.

PMID- 21170742
TI  - Is autophagy in response to ischemia and reperfusion protective or detrimental
      for the heart?
AB  - Autophagy is a catabolic process that degrades long-lived proteins and damaged
      organelles by sequestering them into double membrane structures termed
      "autophagosomes" and fusing them with lysosomes. Autophagy is active in the heart
      at baseline and further stimulated under stress conditions including starvation,
      ischemia/reperfusion, and heart failure. It plays an adaptive role in the heart
      at baseline, thereby maintaining cardiac structure and function and inhibiting
      age-related cardiac abnormalities. Autophagy is activated by ischemia and
      nutrient starvation in the heart through Sirt1-FoxO- and adenosine monophosphate
      (AMP)-activated protein kinase (AMPK)-dependent mechanisms, respectively.
      Activation of autophagy during ischemia is essential for cell survival and
      maintenance of cardiac function. Autophagy is strongly activated in the heart
      during reperfusion after ischemia. Activation of autophagy during reperfusion
      could be either protective or detrimental, depending on the experimental model.
      However, strong induction of autophagy accompanied by robust upregulation of
      Beclin1 could cause autophagic cell death, thereby proving to be detrimental.
      This review provides an overview regarding both protective and detrimental
      functions of autophagy in the heart and discusses possible applications of
      current knowledge to the treatment of heart disease.

PMID- 21170743
TI  - Genetic factors and diet affect long-bone length in the F34 LG,SM advanced
      intercross.
AB  - Previous studies on the LG,SM advanced intercross line have identified
      approximately 40 quantitative trait loci (QTL) for long -bone (humerus, ulna,
      femur, and tibia) lengths. In this study, long-bone-length QTL were fine-mapped
      in the F(34) generation (n = 1424) of the LG,SM advanced intercross.
      Environmental effects were assessed by dividing the population by sex between
      high-fat and low-fat diets, producing eight sex/diet cohorts. We identified 145
      individual bone-length QTL comprising 45 pleiotropic QTL; 69 replicated QTL from
      previous studies, 35 were new traits significant at previously identified loci,
      and 41 were novel QTL. Many QTL affected only a subset of the population based on
      sex and/or diet. Eight of ten known skeletal growth genes were upregulated in 3
      week-old LG/J male proximal tibial growth plates relative to SM/J. The sequences
      of parental strains LG/J and SM/J indicated the presence of over half a million
      polymorphisms in the confidence intervals of these 45 QTL. We examined 526
      polymorphisms and found that 97 represented radical changes to amino acid
      composition while 40 were predicted to be deleterious to protein function.
      Additional experimentation is required to understand how changes in gene
      regulation or protein function can alter the genetic architecture and interact
      with the environment to produce phenotypic variation.

PMID- 21170744
TI  - Interstitial cystitis and endometriosis in a 12-year-old girl.
AB  - INTRODUCTION: Interstitial cystitis (IC) is a common cause of pelvic pain in the
      general female population and is thought to be understated in young female
      patients. CASE: A 12-year-old girl with IC and endometriosis. METHOD: A single
      case report. CONCLUSION: It is important to screen for IC in young patients with
      endometriosis and vice versa.

PMID- 21170745
TI  - Differential expression of microRNA-1 in dorsal root ganglion neurons.
AB  - Damage to sensory neurons induces neural repair, regrowth and hyperexcitability.
      The regulation of such responses to injury must be organized in some way by the
      neurons. Regulation can occur at the post-transcriptional level via microRNAs
      (miRNAs). miRNAs are small non-coding RNAs that influence the stability or
      translation of mRNAs and thereby regulate gene expression. Although nociceptive
      neurons show transcriptional and post-transcriptional regulatory mechanisms at
      many levels, miRNAs have not yet been systematically investigated in these
      neurons. Based on our preliminary array data we investigated the presence of miR
      1 in dorsal root ganglion (DRG) neurons of mice and humans. We detected miR-1 in
      total RNA from human and mouse DRG and localised miR-1 in human and murine
      sensory neurons in situ. In Situ Hybridization detected miR-1 expression by
      nearly all DRG neurons. In vitro studies of enriched sensory neuron
      subpopulations from mouse DRG showed higher miR-1 expression levels in I-B4
      negative neurons compared with I-B4 positive cells. Culturing of primary sensory
      neurons reduced the relative miR-1 expression levels independent of the presence
      or absence of laminin on the culture substrate. Transfection with a miR-1 mimic
      induced a massive increase in neuronal miR-1 associated with attenuated neurite
      outgrowth. This first description of miR-1 in sensory neurons including
      nociceptors suggests that miR-1 has a role in modulating neurite outgrowth.

PMID- 21170746
TI  - A temporal dilution effect: hantavirus infection in deer mice and the
      intermittent presence of voles in Montana.
AB  - The effect of intermittently occurring, non-reservoir host species on pathogen
      transmission and prevalence in a reservoir population is poorly understood. We
      investigated whether voles, Microtus spp., which occur intermittently, influenced
      estimated standing antibody prevalence (ESAP) to Sin Nombre hantavirus (SNV,
      Bunyaviridae: Hantavirus) among deer mice, Peromyscus maniculatus, whose
      populations are persistent. We used 14 years of data from central Montana to
      investigate whether ESAP among deer mice was related to vole presence or
      abundance while controlling for the relationship between deer mouse abundance and
      ESAP. We found a reduction in deer mouse ESAP associated with the presence of
      voles, independent of vole abundance. A number of studies have documented that
      geographic locations which support a higher host diversity can be associated with
      reductions in pathogen prevalence by a hypothesized dilution effect. We suggest a
      dilution effect may also occur in a temporal dimension at sites where host
      richness fluctuates. Preservation of host diversity and optimization of
      environmental conditions which promote occurrence of ephemeral species, such as
      voles, may result in a decreased ESAP to hantaviruses among reservoir hosts. Our
      results may extend to other zoonotic infectious diseases.

PMID- 21170747
TI  - Direct and interaction-mediated effects of environmental changes on peatland
      bryophytes.
AB  - Ecosystem processes of northern peatlands are largely governed by the vitality
      and species composition in the bryophyte layer, and may be affected by global
      warming and eutrophication. In a factorial experiment in northeast China, we
      tested the effects of raised levels of nitrogen (0, 1 and 2 g m(-2) year(-1)),
      phosphorus (0, 0.1 and 0.2 g m(-2) year(-1)) and temperature (ambient and +3
      degrees C) on Polytrichum strictum, Sphagnum magellanicum and S. palustre, to see
      if the effects could be altered by inter-specific interactions. In all species,
      growth declined with nitrogen addition and increased with phosphorus addition,
      but only P. strictum responded to raised temperature with increased production of
      side-shoots (branching). In Sphagnum, growth and branching changed in the same
      direction, but in Polytrichum, the two responses were uncoupled: with nitrogen
      addition there was a decrease in growth (smaller than in Sphagnum) but an
      increase in branching; with phosphorus addition growth increased but branching
      was unaffected. There were no two-way interactions among the P, N and T
      treatments. With increasing temperature, our results indicate that S. palustre
      should decrease relative to P. strictum (Polytrichum increased its branching and
      had a negative neighbor effect on S. palustre). With a slight increase in
      phosphorus availability, the increase in length growth and production of side
      shoots in P. strictum and S. magellanicum may give them a competitive superiority
      over S. palustre. The negative response in Sphagnum to nitrogen could favor the
      expansion of vascular plants, but P. strictum may endure thanks to its increased
      branching.

PMID- 21170748
TI  - Do pollinators influence the assembly of flower colours within plant communities?
AB  - The co-occurrence of plant species within a community is influenced by local
      deterministic or neutral processes as well as historical regional processes.
      Floral trait distributions of co-flowering species that share pollinators may
      reflect the impact of pollinator preference and constancy on their assembly
      within local communities. While pollinator sharing may lead to increased
      visitation rates for species with similar flowers, the receipt of foreign pollen
      via interspecific pollinator movements can decrease seed set. We investigated the
      pattern of community flower colour assembly as perceived by native honeybee
      pollinators within 24 local assemblages of co-flowering Oxalis species within the
      Greater Cape Floristic Region, South Africa. To explore the influence of
      pollinators on trait assembly, we assessed the impact of colour similarity on
      pollinator choices and the cost of heterospecific pollen receipt. We show that
      flower colour is significantly clustered within Oxalis communities and that this
      is not due to historical constraint, as flower colour is evolutionarily labile
      within Oxalis and communities are randomly structured with respect to phylogeny.
      Pollinator observations reveal that the likelihood of pollinators switching
      between co-flowering species is low and increases with flower colour similarity.
      Interspecific hand pollination significantly reduced seed set in the four Oxalis
      species we investigated, and all were dependant on pollinators for reproduction.
      Together these results imply that flower colour similarity carries a potential
      fitness cost. However, pollinators were highly flower constant, and remained so
      despite the extreme similarity of flower colour as perceived by honeybees. This
      suggests that other floral traits facilitate discrimination between similarly
      coloured species, thereby likely resulting in a low incidence of interspecific
      pollen transfer (IPT). If colour similarity promotes pollinator attraction at the
      community level, the observed clustering of flower colour within communities
      might result from indirect facilitative interactions.

PMID- 21170749
TI  - Strong microsite control of seedling recruitment in tundra.
AB  - The inclusion of environmental variation in studies of recruitment is a
      prerequisite for realistic predictions of the responses of vegetation to a
      changing environment. We investigated how seedling recruitment is affected by
      seed availability and microsite quality along a steep environmental gradient in
      dry tundra. A survey of natural seed rain and seedling density in vegetation was
      combined with observations of the establishment of 14 species after sowing into
      intact or disturbed vegetation. Although seed rain density was closely correlated
      with natural seedling establishment, the experimental seed addition showed that
      the microsite environment was even more important. For all species, seedling
      emergence peaked at the productive end of the gradient, irrespective of the adult
      niches realized. Disturbance promoted recruitment at all positions along the
      environmental gradient, not just at high productivity. Early seedling emergence
      constituted the main temporal bottleneck in recruitment for all species.
      Surprisingly, winter mortality was highest at what appeared to be the most benign
      end of the gradient. The results highlight that seedling recruitment patterns are
      largely determined by the earliest stages in seedling emergence, which again are
      closely linked to microsite quality. A fuller understanding of microsite effects
      on recruitment with implications for plant community assembly and vegetation
      change is provided.

PMID- 21170750
TI  - Modelling the effect of directional spatial ecological processes at different
      scales.
AB  - During the last 20 years, ecologists discovered the importance of including
      spatial relationships in models of species distributions. Among the latest
      developments in modelling how species are spatially structured are eigenfunction
      based spatial filtering methods such as Moran's eigenvector maps (MEM) and
      principal coordinates of neighbour matrices (PCNM). Although these methods are
      very powerful and flexible, they are only suited to study distributions resulting
      from non-directional spatial processes. The asymmetric eigenvector map (AEM)
      framework, a new eigenfunction-based spatial filtering method, fills this
      theoretical gap. AEM was specifically designed to model spatial structures
      hypothesized to be produced by directional spatial processes. Water currents,
      prevailing wind on mountainsides, river networks, and glaciations at historical
      time scales are some of the situations where AEM can be used. This paper presents
      three applications of the method illustrating different combinations of: sampling
      schemes (regular and irregular), data types (univariate and multivariate), and
      spatial scales (metres, kilometres, and hundreds of kilometres). The applications
      include the distribution of a crustacean (Atya) in a river, bacterial production
      in a lake, and the distribution of the copepodite stages of a crustacean on the
      Atlantic oceanic shelf. In each application, a comparison is made between AEM,
      MEM, and PCNM. No environmental components were included in the comparisons. AEM
      was a strong predictor in all cases, explaining 59.8% for Atya distribution,
      51.4% of the bacterial production variation, and 38.4% for the copepodite
      distributions. AEM outperformed MEM and PCNM in these applications, offering a
      powerful and more appropriate tool for spatial modelling of species distributions
      under directional forcing and leading to a better understanding of the processes
      at work in these systems.

PMID- 21170751
TI  - Non-linear density-dependent effects of an intertidal ecosystem engineer.
AB  - Ecosystem engineering is an important process in a variety of ecosystems.
      However, the relationship between engineer density and engineering impact remains
      poorly understood. We used experiments and a mathematical model to examine the
      role of engineer density in a rocky intertidal community in northern California.
      In this system, the whelk Nucella ostrina preys on barnacles (Balanus glandula
      and Chthamalus dalli), leaving empty barnacle tests as a resource (favorable
      microhabitat) for other species. Field experiments demonstrated that N. ostrina
      predation increased the availability of empty tests of both barnacle species,
      reduced the density of the competitively dominant B. glandula, and indirectly
      increased the density of the competitively inferior C. dalli. Empty barnacle
      tests altered microhabitat humidity, but not temperature, and presumably provided
      a refuge from wave action. The herbivorous snail Littorina plena was positively
      associated with empty test availability in both observational comparisons and
      experimental manipulations of empty test availability, and L. plena density was
      elevated in areas with foraging N. ostrina. To explore the effects of variation
      in N. ostrina predation, we constructed a demographic matrix model for barnacles
      in which we varied predation intensity. The model predicted that number of
      available empty tests increases with predation intensity to a point, but declines
      when predation pressure was strong enough to severely reduce adult barnacle
      densities. The modeled number of available empty tests therefore peaked at an
      intermediate level of N. ostrina predation. Non-linear relationships between
      engineer density and engineer impact may be a generally important attribute of
      systems in which engineers influence the population dynamics of the species that
      they manipulate.

PMID- 21170752
TI  - The oversight and practice of oocyte donation in the United States, United
      Kingdom and Canada.
AB  - In vitro fertilization using donated oocytes is an important medical technique
      that provides the only option for some infertile patients to have children. The
      technique remains ethically contentious, however, and, as a result of this
      controversy, different oversight approaches have been developed in countries
      around the world. This paper examines the oversight and practice of oocyte
      donation in Canada, the United Kingdom and the United States to examine how
      policy choices have influenced the development and use of this medical
      technology. Examining per capita utilization of oocyte donation in these three
      countries provides evidence that supply-side policies-specifically policies
      affecting the compensation of potential oocyte donors-have substantially
      influenced the use of this technology. These results should provide useful
      insight for policymakers developing or revising oocyte donation policies.

PMID- 21170753
TI  - Bioethics training in Uganda: report on research and clinical ethics workshops.
AB  - This essay describes and critically evaluates a co-operative educational program
      to train Ugandan health care workers in bioethics. It describes one "bottom-up"
      effort, a week-long intensive workshop in bioethics provided by the authors to
      health care professionals in a developing country-Uganda. We will describe the
      background and circumstances that led to the organization of the workshop, and
      review its planning, design, curriculum, and outcome. We will focus especially on
      measures taken to make the workshop relevant for the audience of Ugandan
      professionals, and describe lessons learned after two presentations of the
      workshop. Finally, we will discuss the strengths and weaknesses of such a format,
      and its potential value in raising bioethical expertise in developing countries.

PMID- 21170754
TI  - The associations between statin use and prostate cancer screening, prostate size,
      high-grade prostatic intraepithelial neoplasia (PIN), and prostate cancer.
AB  - OBJECTIVE: Prior studies report statins may reduce the risk of advanced prostate
      cancer. This study investigates the association between statin use and the
      likelihood of having a PSA or DRE test, blood PSA levels, prostate volume, and
      the severity of lower urinary tract symptoms. We also describe the association
      between statin use and prostate cancer and high-grade prostatic intraepithelial
      neoplasia (PIN) before and after controlling for prostate cancer screening
      indices associated with statin use. METHODS: The Nashville Men's Health Study
      used a multicenter, rapid recruitment protocol to collect clinical, biologic,
      behavioral, and body measurement data from 2,148 men 40 years or older scheduled
      for diagnostic prostate biopsy. Medication use and other data were ascertained by
      research survey, clinical interview, and chart review. RESULTS: Approximately 37%
      of participants were taking a statin. Statin use was significantly associated
      with a 12% lower PSA levels and 8% smaller prostate volume after controlling for
      age, race, BMI, WHR, aspirin use, and other comorbidity. Simvastatin was more
      strongly associated with prostate volume, while atorvastatin was associated with
      PSA. Statin use was marginally associated with increasing PSA test frequency
      among men with undiagnosed cancer. Statin use was not associated with the
      frequency or results of digital rectal exams, lower urinary tract symptom
      severity, high-grade (Gleason > 6) prostate cancer (OR = 0.95 (0.73, 1.24)), low
      grade (Gleason = 6) prostate cancer (OR = 1.11 (0.86, 1.42)) or PIN (OR = 0.82,
      (0.57, 1.17)). Additional control for the number of prior PSA tests, PSA levels,
      and prostate volume did not alter these results. CONCLUSION: These results
      suggest selective referral for biopsy associated with statin use is an essential
      element to address in further understanding the potential for statins to prevent
      prostate cancer.

PMID- 21170755
TI  - Efalizumab, a human monoclonal anti-CD11a antibody, in the treatment of moderate
      to severe Crohn's Disease: an open-label pilot study.
AB  - BACKGROUND AND AIMS: Efalizumab is a monoclonal antibody targeting CD11a, an
      adhesion molecule involved in the activation and trafficking of T-lymphocytes.
      This agent has proven efficacy in the treatment of psoriasis. We performed an
      open-label study to evaluate the efficacy and safety of efalizumab in Crohn's
      disease (CD). METHODS: Fifteen subjects with moderate to severe CD (Crohn's
      Disease Activity Index [CDAI] score 220-450) and who were refractory or
      intolerant to standard therapy, received a weekly 1 mg/kg subcutaneous injection
      of efalizumab for 8 weeks. The primary endpoint was clinical response (decrease
      in the CDAI score of at least 70 points) at week 8. Secondary endpoints included
      change in mean CDAI scores, the proportion of subjects who achieved clinical
      remission (CDAI score <= 150), change in the Inflammatory Bowel Disease
      Questionnaire (IBDQ) scores, and report of adverse events. RESULTS: At 8 weeks,
      ten (67%) subjects had clinical response and six (40%) were in remission. The
      mean baseline and week 8 CDAI scores were 300 and 167 respectively (P < 0.001).
      Mean IBDQ scores at baseline and week 8 were 124 and 168 respectively (P <
      0.001). One subject with Crohn's colitis had pre- and post-treatment colonoscopy
      that demonstrated mucosal healing. No serious adverse events occurred.
      CONCLUSIONS: Efalizumab induced a clinical response in the majority of subjects
      with moderate to severe CD in this small, open-label pilot study. There were no
      serious adverse events reported during this short-term trial.

PMID- 21170756
TI  - Necrotizing fasciitis with fatal outcome: a report of two cases.
AB  - Two cases of sudden and unexpected death due to necrotizing fasciitis are
      presented with a short overview of this rare disease with special reference to
      pathological features and causative and epidemiological factors. One case
      occurred as a complication of liposuction surgery, and the second presented after
      minor trauma. Based on the autopsy findings and an interdisciplinary approach,
      medico-legal evaluation provides a substantial basis for later court hearings in
      such cases.

PMID- 21170757
TI  - A fast intraoperative PTH point-of-care assay on the Philips handheld magnotech
      system.
AB  - BACKGROUND: Intraoperative parathyroid hormone (ioPTH) is used during minimally
      invasive parathyroidectomy (MIP) to predict the success of surgery and should be
      accurate with a short turnaround time. MATERIAL AND METHOD: We developed an ioPTH
      point-of-care (POC) assay on Philips handheld magnotech system. Magnotech
      technology is based on magnetically controlled movement of superparamagnetic
      nanoparticles in stationary sample fluid. During first phase, intact-PTH is
      captured by magnetic particles coated with anti-N-terminal-PTH antibodies.
      Subsequently, magnetic particles are collected by magnetic forces at sensor
      surface coated with anti-C-terminal-PTH antibodies. Unbound/nonspecifically bound
      particles are pulled away from detection surface, using a second magnetic force.
      Amount of specifically bound particles is measured using a surface-sensitive
      optical imaging technique. RESULTS: ioPTH test could be performed with a
      turnaround time of less than 10 min and could detect low intact-PTH
      concentrations (picomolar). Integrated cartridge contains a blood separation
      filter and dry reagents for the assay. CONCLUSION: The next magnotech ioPTH assay
      will be the only POC test able to give accurate results in less than 10 min,
      using 25 MUL of whole blood. Thanks to the ease-of-use, magnotech ioPTH could be
      performed in the operating theater by any member of surgical staff.

PMID- 21170758
TI  - Usefulness of 3-month protocol biopsy of kidney allograft to detect subclinical
      rejection under triple immunosuppression with basiliximab: a single center
      experience.
AB  - BACKGROUND: Theoretically, an early protocol biopsy (PB) serves to detect
      subclinical rejection (SCR), allowing early treatment and prevention of acute
      rejection (AR) and chronic graft injuries. In this retrospective study, we
      investigated the incidence of biopsy-proven AR (BPAR) and the usefulness of a 3
      month PB in detecting SCR in kidney transplant (KT) and simultaneous pancreas
      kidney transplant (SPKT) recipients who received triple immunosuppression and
      basiliximab. METHODS: Between January 2007 and September 2009, 116 patients
      received transplantation (KT = 112, SPKT = 4). In August 2008, we changed our PB
      policy and started to collect PB after 3 months instead of a pre-discharge biopsy
      performed 1 month after transplantation. Here we compare the incidence of SCR
      (defined as Banff grade Ia or higher) between the pre-discharge PB group and the
      3-month PB group. PB was obtained from 41 patients before discharge (pre
      discharge PB group), and from 49 patients 3 months after transplantation (3-month
      PB group). RESULTS: Among all recipients, 21 patients were diagnosed with BPAR
      (estimated incidence of BPAR 20.1%); including 13 (62.0%) diagnosed from 31 to
      180 postoperative days (POD), and only 3 (14.3%) within 30 POD. The incidence of
      BPAR was not different between the two groups (19.5 and 20.8%, respectively);
      however, 4 of 8 recipients in the 3-month PB group were diagnosed with SCR,
      compared to none in the pre-discharge PB group (P < 0.05). CONCLUSION: Since the
      use of triple immunosuppression and basiliximab delayed the onset of AR, we
      recommend that in order to detect SCR, PB should be obtained 3 months
      postoperatively.

PMID- 21170759
TI  - Phase II study of nimotuzumab, a humanized monoclonal anti-epidermal growth
      factor receptor (EGFR) antibody, in patients with locally advanced or metastatic
      pancreatic cancer.
AB  - INTRODUCTION: Nimotuzumab is a humanized monoclonal antibody that binds to the
      EGFR. Based on phase I data, the recommended dose has been established at 200 mg
      weekly. This study was aimed at evaluating the safety and efficacy of nimotuzumab
      monotherapy in patients (pts) with locally advanced or metastatic pancreatic
      cancer. METHODS: Pts who failed first line standard chemotherapy for advanced
      disease and had at least one measurable lesion were eligible for the study.
      Nimotuzumab was given intravenously at 200 mg once weekly for 6 weeks (wks).
      Follow up by CT scan was performed after 8 weeks. Pts continued receiving
      treatment 3-weekly until disease progression or unacceptable toxicity occurred.
      Endpoints included tumor response (RECIST), progression-free survival (PFS), and
      safety. RESULTS: A total of 56 pts were enrolled for treatment (ECOG status of 1
      [n = 41] or 0 [n = 15]), the majority (47 pts) had metastatic disease. Nearly
      half of the pts [n = 26] received >=2 regimens. Pts evaluable for response: n =
      36; CR: 0; PR: 0; SD: 6 pts. Median PFS for pts with SD was 19.2 weeks, for all
      pts 6.7 weeks (95% CI: 6.43-7.14 weeks). PFS after 1 year was 10.3% with a median
      overall survival of 18.1 weeks. Treatment-related adverse events were generally
      mild including rash grade 1 in 5 pts. After a single dose of 200 mg, the t(1/2)
      was calculated to 45 h. CONCLUSION: These data confirm that nimotuzumab is safe
      and very well tolerated. To improve efficacy, a randomized, placebo-controlled
      trial with Gem has been initiated.

PMID- 21170760
TI  - Enhanced oncolysis mediated by Coxsackievirus A21 in combination with doxorubicin
      hydrochloride.
AB  - Virotherapy is an emerging strategy for the treatment of cancer that utilizes
      both replication-competent and genetically modified viruses to selectively kill
      tumor cells. We have previously shown that Coxsackievirus A21 (CVA21), a common
      cold producing enterovirus, is an effective oncolytic agent against human
      melanoma, prostate, and breast cancer xenografts in vivo. CVA21 specifically
      targets and lytically infects susceptible cells expressing the CVA21 cellular
      receptors, intercellular adhesion molecule-1 (ICAM-1) and decay-accelerating
      factor (DAF). Herein, the efficacy of CVA21 administered in combination with
      doxorubicin hydrochloride as a new therapeutic regimen for cancer was
      investigated. Flow cytometric analysis demonstrated that the human breast,
      colorectal, and pancreatic cancer cell lines examined expressed moderate levels
      of surface ICAM-1 and DAF, whilst a normal breast cell line expressed only
      minimal levels. When CVA21 was combined with doxorubicin hydrochloride,
      synergistically enhanced cell death was observed when CVA21 was administered both
      simultaneously or 24 h prior to doxorubicin hydrochloride exposure. Doxorubicin
      hydrochloride had no effect on CVA21 replication. Through the use of an
      orthotopic (MDA-MB-231-luc) xenograft SCID mouse model of human breast cancer we
      showed that a single intravenous injection of CVA21 in combination with an
      intraperitoneal injection of doxorubicin hydrochloride resulted in significantly
      greater tumor reduction compared to either agent alone. Overall, these findings
      highlight the exciting potential of CVA21, administered in combination with
      doxorubicin hydrochloride, as a new therapeutic regimen for cancer.

PMID- 21170762
TI  - Bronchoscopic lung volume reduction--current opinion.
AB  - Bronchoscopic lung volume reduction is a new technology designed to reduce
      hyperinflation in severe COPD by implantation of endobronchial devices, such as
      biodegradable material, endobronchial valves or bronchopulmonary stents, via
      flexible bronchoscopy. This article discusses newest developments and results in
      bronchoscopic lung volume reduction.

PMID- 21170763
TI  - Current developments in the use of stem cell for therapeutic neovascularisation:
      is the future therapy "cell-free"?
AB  - The plasticity and self-regenerative properties of stem cells have opened new
      avenues in regenerative medicine. Greater understanding of the biology of stem
      cells is followed by growing expectations of a rapid translation into alternative
      therapeutic options. Recent preclinical studies and clinical trials employing
      stem and progenitor cells from different sources have shown encouraging results.
      However, their underlying mechanisms are still poorly understood, the potential
      adverse effects and the discrepancy in efficacy remain to be further
      investigated. Their essential role in vessel regeneration has made endothelial
      progenitor cells (EPC) a suitable candidate for therapeutic applications aiming
      at tissue revascularisation. Recent evidence suggests that EPC contribute to
      neovascularisation not only by direct participation in tissue homeostasis but
      mainly via paracrine mechanisms. In future, novel therapeutic strategies could be
      based on EPC paracrine factors or synthetic factors, and replace cell
      transplantation.

PMID- 21170764
TI  - Community home-based care - a cost-effective model of care: who benefits?
AB  - Statistics indicate that the HIV and AIDS pandemic is rampant in the province of
      KwaZulu-Natal (KZN). Increasingly, people with HIV and AIDS rely on voluntary
      community home-based caregivers for care and support. Drawing on original
      research conducted in 2005 and a subsequent study in 2009, this article presents
      the socio-economic context of care and women's perspectives on care giving. The
      study was conducted in three different communities in KZN. The feminist post
      structuralist perspective provided the theoretical framework. Data collection
      methods included in-depth semi-structured interviews, observations and
      documentary review. The data were analysed using the grounded theory approach.
      The study revealed that it is poor, black, unemployed Zulu women who provide
      community home-based care (CHBC) in the province. The findings further suggested
      that the CHBC programme overlooks the realities of women, who operate in a
      context of poverty and unemployment. It is therefore argued that while the
      National HIV and AIDS Strategic Plan 2007-2011 has made progressive strides,
      implementation of the set targets remains a formidable challenge. In practice,
      the Plan remains gender-blind to poor women's social, political and economic
      imperatives. The article proposes a model of care that takes into cognisance the
      interests of women caregivers.

PMID- 21170761
TI  - Mesenchymal stem cells in the pathogenesis and therapy of breast cancer.
AB  - Mesenchymal stem cells (MSCs) are a heterogeneous mix of stromal stem cells that
      can give rise to cells of mesodermal lineages, namely adipocytes, osteocytes and
      chondrocytes. They can home to sites of injury where they promote the repair and
      regeneration of damaged tissues. MSCs also home to sites of tumorigenesis, and as
      such, are utilized as efficient cellular vehicles for the delivery of anti
      neoplastic therapeutics. Recently, MSCs within the tumor microenvironment have
      been shown to contribute to the desmoplastic reaction and to facilitate tumor
      formation and progression, sparking renewed interest in their pro-tumorigenic
      attributes and their roles as tumor stromal cells. Here, we describe the evidence
      linking MSCs to inflammatory processes and breast cancer development, and discuss
      their newly discovered physiological roles in the context of the tumor
      microenvironment.

PMID- 21170766
TI  - Is acoustic startle a viable exposure protocol for posttraumatic stress disorder?
      A clinical case study.
AB  - Exaggerated startle is a common symptom (based on Diagnostic and Statistical
      Manual of Mental Disorders [fourth edition] Criterion D) for many patients with
      posttraumatic stress disorder (PTSD). Findings from previous studies suggest that
      exaggerated startle may be due to trauma exposure or pretrauma vulnerability
      factors for PTSD development. The present clinical case study reports on a
      patient with PTSD characterized by a very prominent startle response and
      preference against standard trauma-related exposure strategies. On the basis of
      recent findings that interoceptive exposure exercises (e.g. shaking head side to
      side, hyperventilation) elicit trauma-related memories (Wald & Taylor, 2008), the
      authors sought to determine whether repeated application of an acoustic startle
      stimulus would serve to diminish the prominent startle response and facilitate
      exposure and overall symptom reduction by eliciting trauma-related memories. The
      protocol was successful in eliciting vivid and distressing trauma-related
      memories. Over the course of seven exposure trials, the patient demonstrated a
      decrease in distress elicited during the protocol, improved mood, and reduced
      general anxiety and trauma-related distress. He also reported significantly
      decreased startle response to loud noises encountered during activities of daily
      living. Although preliminary, these finding suggest that the acoustic startle
      protocol may be a viable (interoceptive) exposure strategy for individuals with
      PTSD, particularly those with exaggerated startle responses and those who are not
      amenable to standard trauma-related exposure strategies.

PMID- 21170767
TI  - Towards validation of computational analyses of peri-implant displacements by
      means of experimentally obtained displacement maps.
AB  - Micro-finite element (MUFE) analysis has recently been introduced for the
      detailed quantification of the mechanical interaction between bone and implant.
      The technique has been validated at an apparent level. The aim of this study was
      to address the accuracy of MUFE analysis at the trabecular level. Experimental
      displacement fields were obtained by deformable image registration, also known as
      strain mapping (SM), of dynamic hip screws implanted in three human femoral
      heads. In addition, displacement fields were calculated using MUFE analysis. On a
      voxel-by-voxel basis, the coefficients of determination (R(2)) between
      experimental and MUFE-calculated displacements ranged from 0.67 to 0.92. Linear
      regression of the mean displacements over nine volumes of interest yielded R(2)
      between 0.81 and 0.84. The lowest R(2) values were found in regions of very small
      displacements. In conclusion, we found that peri-implant bone displacements
      calculated with MUFE analysis correlated well with displacements obtained from
      experimental SM.

PMID- 21170768
TI  - Stress transfer properties of different commercial dental implants: a finite
      element study.
AB  - Dental implantology has high success rates, and a suitable estimation of how
      stresses are transferred to the surrounding bone sheds insight into the correct
      design of implant features. In this study, we estimate stress transfer properties
      of four commercial implants (GMI, Lifecore, Intri and Avinent) that differ
      significantly in macroscopic geometry. Detailed three-dimensional finite element
      models were adopted to analyse the behaviour of the bone-implant system depending
      on the geometry of the implant (two different diameters) and the bone-implant
      interface condition. Occlusal static forces were applied and their effects on the
      bone, implant and bone-implant interface were evaluated. Large diameters avoided
      overload-induced bone resorption. Higher stresses were obtained with a debonded
      bone-implant interface. Relative micromotions at the bone-implant interface were
      within the limits required to achieve a good osseointegration. We anticipate that
      the methodology proposed may be a useful tool for a quantitative and qualitative
      comparison between different commercial dental implants.

PMID- 21170769
TI  - Mixed-mode loading of the cement-bone interface: a finite element study.
AB  - While including the cement-bone interface of complete cemented hip
      reconstructions is crucial to correctly capture their response, its modelling is
      often overly simplified. In this study, the mechanical mixed-mode response of the
      cement-bone interface is investigated, taking into account the effects of the
      well-defined microstructure that characterises the interface. Computed tomography
      based plain strain finite element analyses models of the cement-bone interface
      are built and loaded in multiple directions. Periodic boundaries are considered
      and the failure of the cement and bone fractions by cracking of the bulk
      components are included. The results compare favourably with experimental
      observations. Surprisingly, the analyses reveal that under shear loading no
      failure occurs and considerable normal compression is generated to prevent
      interface dilation. Reaction forces, crack patterns and stress fields provide
      more insight into the mixed-mode failure process. Moreover, the cement-bone
      interface analyses provide details which can serve as a basis for the development
      of a cohesive law.

PMID- 21170770
TI  - Somatic complaint differences between Turkish immigrants and Belgians: do all
      roads lead to Rome?
AB  - OBJECTIVE: Turkish immigrants have been found to report more somatic complaints
      compared to western majority groups. The present study investigates the
      combination of two cultural explanations (somatization versus psychologization
      and emotion mediation) with two acculturative explanations (acculturative stress
      versus acculturative transition) to explain these differences. DESIGN: In total,
      144 Turkish immigrants, 353 Belgian majority members, and 222 Turkish majority
      members were asked to report the last three emotional episodes they encountered
      and to rate them on 24 emotion terms and 17 somatic sensations. RESULTS: Turkish
      majorities scored higher on all somatic factors, anxiety-sadness, and self
      conscious emotions followed by Turkish immigrants and Belgian majorities.
      Furthermore, path analysis showed (partial) mediation effects of anxiety-sadness
      and self-conscious factors on the differences in the somatic factors between
      Belgian and Turkish majorities. CONCLUSION: These results indicate that the
      somatic differences do not result from a trade-off between somatization and
      psychologization, but that emotions mediate differences in somatic processes to a
      large extent. It was also found that differences between Turkish immigrants and
      Belgian majority members are to be attributed to acculturative transition, rather
      than to acculturative stress.

PMID- 21170771
TI  - Health is a spiritual thing: perspectives of health care professionals and female
      Somali and Bangladeshi women on the health impacts of fasting during Ramadan.
AB  - OBJECTIVE: To explore perspectives of health care professionals and female Somali
      and Bangladeshi Muslim women on practices related to fasting during Ramadan, the
      impact of fasting on health and the role of health professionals during Ramadan.
      DESIGN: A cross-sectional qualitative study was conducted. Two culturally
      specific focus groups were conducted with six Somali and seven Bangladeshi Muslim
      women who observed Ramadan and lived in an inner-city neighbourhood of Toronto,
      Canada. Individual semi-structured interviews were conducted with 22 health care
      professionals practicing in this inner-city area (three of whom were Muslim).
      Data were analysed using thematic qualitative analysis. RESULTS: Both Muslim
      women and health care professionals recognised the spiritual significance of the
      Ramadan fast. Muslim participants considered the fast to be beneficial to health
      overall, whereas health care professionals tended to reflect on health concerns
      from fasting. Many health care professionals were not fully aware of fasting
      practices during Ramadan and some found it challenging to counsel patients about
      the health effects of fasting. Muslim women expressed disagreement regarding
      which medical interventions were permitted during fasting. They generally agreed
      that health care professionals should not specifically advise against fasting,
      but instead provide guidance on health maintenance while fasting. Both groups
      agreed that guidelines developed by the health care and faith communities
      together would be useful. CONCLUSION: There are a variety of health beliefs and
      observances among female Muslim Somali and Bangladeshi women and a range of
      knowledge, experience and opinions among health care professionals related to
      fasting during Ramadan and health. Overall, there is a need for improved
      communication between members of the Muslim community and health professionals in
      Canada about health issues related to fasting during Ramadan. Strategies could
      include published practice guidelines endorsed by the Muslim community; patient
      education materials developed in collaboration with health and religious experts;
      or further qualitative research to help professionals understand the beliefs and
      observances of Muslim people.

PMID- 21170772
TI  - Effects of perfluorooctane sulfonate (PFOS) exposure on markers of inflammation
      in female B6C3F1 mice.
AB  - Perfluorooctane sulfonate (PFOS; 1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8
      heptadecafluoro-1-octanesulfonic acid) has been reported to alter humoral immune
      functions, but inflammatory processes following PFOS exposure have not been fully
      characterized. Therefore, the current study, assessed TNF-alpha and IL-6
      concentrations in serum and peritoneal lavage fluid, numbers of splenoctyes
      expressing intracellular TNF-alpha, IL-6, IL-10 or IL-1, and ex vivo TNF-alpha
      and IL-6 production by peritoneal macrophages following either in vivo or in
      vitro LPS exposure. Adult female B6C3F1 mice were exposed orally for 28 days to
      0, 1, 3, or 300 mg PFOS/kg total administered dose [TAD] (e.g., 0, 0.0331, 0.0993
      or 9.93 mg/kg/day). Body and spleen masses were significantly reduced in the
      highest PFOS treatment group compared to the control group, whereas liver mass
      was significantly increased. Serum TNF-alpha levels were significantly decreased
      following exposure to 1 mg PFOS/kg TAD as compared to controls, while serum IL-6
      levels were increased. IL-6 concentrations in peritoneal lavage fluid decreased
      with increasing dose. PFOS treatment did not alter numbers of splenocytes
      expressing intracellular levels of TNF-alpha, IL-10 or IL-1. Numbers of
      splenocytes expressing intracellular levels of IL-6 were significantly decreased
      in the 3 mg/kg treatment as compared to controls. Overall, these data suggest
      that PFOS exposure can alter some inflammatory processes, which could potentially
      lead to misdirected inflammatory responses.

PMID- 21170773
TI  - Sex- and age-dependent accumulation of heavy metals (Cd, Pb and Zn) in liver,
      kidney and muscle of roe deer (Capreolus capreolus) from NW Spain.
AB  - In the present study, bioaccumulation of lead, cadmium and zinc in liver, kidney
      and muscle of roe deer (Capreolus capreolus) from Galicia (NW Spain) was
      quantified. Metal analysis was performed by Inductively Coupled Plasma Mass
      Spectrometry (ICP-MS). In general the quantified concentrations were associated
      with background environmental levels, except for Pb, where some markedly elevated
      concentrations were obtained, but with no toxicological relevance. The effect of
      sex on Cd, Pb and Zn levels was considered, females showing a general trend to
      accumulate higher concentrations of these metals, with the exception of the
      hepatic content of Cd (which was significantly higher in males, P < 0.05) and Pb
      levels, which did not differ according to sex. The effect of age was analysed
      only in male animals and was clearly observed for Pb levels, with concentrations
      significantly higher in adult animals (liver: P < 0.01, kidney: P < 0.05 and
      muscle: P < 0.001) and for Cd levels in kidney samples (P < 0.001). This study
      provides the first data on heavy metal content in roe deer from the area of study
      and suggests that this species could be a good bioindicator of metal pollution,
      even though both factors, sex and age, could represent an important source of
      variation in the bioaccumulation of these metals in wild populations.

PMID- 21170774
TI  - Interaction of acid mine drainage with Ordinary Portland Cement blended solid
      residues generated from active treatment of acid mine drainage with coal fly ash.
AB  - Fly ash (FA) has been investigated as a possible treatment agent for Acid mine
      drainage (AMD) and established to be an alternative, cheap and economically
      viable agent compared to the conventional alkaline agents. However, this
      treatment option also leads to generation of solid residues (SR) that require
      disposal and one of the proposed disposal method is a backfill in coal mine
      voids. In this study, the interaction of the SR with AMD that is likely to be
      present in such backfill scenario was simulated by draining columns packed with
      SR and SR + 6% Ordinary Portland Cement (OPC) unsaturated with simulated AMD over
      a 6 month period. The evolving geochemistry of the liquid/solid (L/S) system was
      evaluated in-terms of the mineral phases likely or controlling contaminants
      attenuation at the different pH regimes generated. Stepwise acidification of the
      percolates was observed as the drainage progressed. Two pH buffer zones were
      observed (7.5-9 and 3-4) for SR and (11.2-11.3 and 3.5-4) for SR + 6% OPC. The
      solid residue cores (SR) appeared to have a significant buffering capacity,
      maintaining a neutral to slightly alkaline pH in the leachates for an extended
      period of time (97 days: L/S 4.3) while SR + 6% OPC reduced this neutralization
      capacity to 22 days (L/S 1.9). Interaction of AMD with SR or SR + 6% OPC
      generated alkaline conditions that favored precipitation of Fe, Al, Mn-(oxy)
      hydroxides, Fe and Ca-Al hydroxysulphates that greatly contributed to the
      contaminants removal. However, precipitation of these phases was restricted to
      the pH of the leachates remaining at neutral to circum-neutral levels. Backfill
      of mine voids with SR promises to be a feasible technology for the disposal of
      the SR but its success will greatly depend on the disposal scenario, AMD
      generated and the alkalinity generating potential of the SR. A disadvantage would
      be the possible re-dissolution of the precipitated phases at pH < 4 that would
      release the contaminants back to the water column. However extrapolation of this
      concept to a field scenario can greatly enhance beneficial application of fly ash
      (FA) and solid residues (SR) generated from treatment of AMD.

PMID- 21170775
TI  - Scots pine bark, topsoil and pedofauna as indicators of transport pollutions in
      terrestrial ecosystems.
AB  - The impact of the motorway on pollution was evaluated by determining chosen heavy
      metals and acid reaction (pH) in the pine bark, in forest and meadow topsoil. The
      content of these environmental contaminants was determined in the topsoil and in
      the bark of around 40 year-old Scots pines (Pinus sylvestris L.) growing right
      next to the soil analyzed. The pollutants were examined at localities situated
      around 5, 200, 1500 m away from the motorway. To evaluate influence of Cd, Pb,
      Zn, Cu and the topsoil pH on pedofauna, five meadows localities situated 1, 20,
      40, 150, 1550 m away from the motorway were examined. It was detected that in the
      forest habitats analyzed the bark was characterized by considerably higher
      acidity (pH 3.14-3.88) than the topsoil of the pines analyzed (pH 5.45-7.22).
      Except of Cd at locality 200 m and Cu at 1500 m from motorway, the higher
      concentration of heavy metals was noted in topsoil. In the meadow soil of the
      locality 150 m from the motorway the highest concentrations of Cd and Zn were
      detected. The greatest diversity of the meso and macrofauna and trophic relations
      the most resembling natural were detected in the area furthest away from the
      motorway, where the content of the heavy metals was the lowest. The lowest
      density and diversity of meso- and macrofauna were detected in the area situated
      40 m, where the concentration of heavy metals was higher than at 1, 20 and 1550 m
      from the motorway situated localities.

PMID- 21170776
TI  - Deficit commission targets social security: privatization revisited?

PMID- 21170778
TI  - Decoding the Miss Daisy Syndrome: an examination of subjective responses to
      mobility change.
AB  - The subjective responses associated with personal life space and mobility status
      were explored. Thirty individuals participated in focus groups based on self
      rated disability status, current places visited, and availability. Qualitative
      analyses revealed that most participants equated personal mobility with driving a
      vehicle. Attitudes concerning mobility status and preparedness for change varied
      based on disability level and personal experience. Fear of dependence from future
      mobility loss was prominent in all groups. Few participants acknowledged
      significant planning for future retirement from driving or other mobility
      challenges. An understanding of common attitudes, perceptions and meanings can
      inform professionals who intervene and support older adults experiencing mobility
      changes.

PMID- 21170777
TI  - Anxiety and related symptoms in older persons with dementia: directions for
      practice.
AB  - Anxiety disorders and related symptoms commonly occur in older people with
      cognitive impairment or dementia, significantly worsening functioning and
      reducing quality of life. This review of the literature outlines the extent of
      the problem, and focuses on current best practices in psychosocial interventions
      anxiety in persons with dementia. Discussion follows on promising
      nonpharmacological interventions that are recommended for further consideration
      and future research.

PMID- 21170779
TI  - Assisted living facility administrator and direct care staff views of resident
      mental health concerns and staff training needs.
AB  - This community needs assessment surveyed 21 administrators and 75 direct care
      staff at 9 larger and 12 smaller assisted living facilities (ALFs) regarding
      perceptions of resident mental health concerns, direct care staff capacity to
      work with residents with mental illness, and direct care staff training needs.
      Group differences in these perceptions were also examined. Both administrators
      and directcare staff indicated that direct care staff would benefit from mental
      health-related training, and direct care staff perceived themselves as being more
      comfortable working with residents with mental illness than administrators
      perceived them to be. Implications for gerontological social work are discussed.

PMID- 21170780
TI  - From interviewers to friendly visitors: bridging research and practice to meet
      the needs of low-income Latino seniors.
AB  - This article describes a community-based participatory research (CBPR) effort
      conducted in a low-income, predominantly Latino community, which bridged
      traditionally-separate domains of practice and research by engaging neighborhood
      residents in a collaborative capacity-enhancement process for meeting the needs
      of vulnerable elderly residents. What began as a simple needs assessment to
      facilitate program development became a mechanism for engaging neighborhood
      residents in a collaborative social capital development process. The article
      describes the origins of this community-based effort, its consumer-led
      transformation from traditional needs assessment to service provision, resulting
      benefits and challenges, and implications for meeting the needs of vulnerable
      populations.

PMID- 21170781
TI  - Informal caregivers of cancer patients: perceptions about preparedness and
      support during hospice care.
AB  - This study examined the perceptions of preparedness and support of informal
      caregivers of hospice oncology patients. Respondents included coresiding,
      proximate, and long-distance caregivers. Thematic analysis was used to analyze
      the qualitative data from 2 caregiver surveys, one administered prior to the care
      recipient's death and another completed 3 months postdeath. Respondents (N = 69)
      interpreted preparedness broadly and identified multiple sources of support
      including hospice personnel, family, friends, neighbors, and spiritual beliefs.
      Additionally, informational support, such as education, information, and enhanced
      communication were considered essential for preparing and supporting caregivers.
      Implications for social work research and practice are provided.

PMID- 21170784
TI  - Testimony on achieving Millennium Development Goals.

PMID- 21170782
TI  - Boomers' prospective needs for senior centers and related services: a survey of
      persons 50-59.
AB  - The future service needs of baby boomers are unclear. A survey addressing
      work/retirement, family, civic engagement, health, caregiving, leisure, and
      perceptions of senior services was mailed to 800 addresses randomly selected from
      a upper Midwestern county voter registration list. The response rate was 28%.
      Fifty-three percent of the respondents (N = 225) intended to work and increase
      civic engagement. They expected more time for hobbies and friends, and to travel
      more. Family will continue to be their highest priority. These findings will be
      useful to service providers who are invested in providing services that are
      attractive to boomers.

PMID- 21170785
TI  - The effects of sensation seeking, misperceptions of peer consumption, and
      believability of social norms messages on alcohol consumption.
AB  - The social norms marketing approach is one method used to reduce extreme alcohol
      consumption. The current study implemented a web-based survey (N = 891) to assess
      whether sensation-seeking, perceived moderate drinking norms, and social norm
      message believability impacted alcohol consumption on a college campus. Sensation
      seeking was not directly related to normative perceptions of others' moderate
      alcohol consumption. Sensation seeking, perceived norms, and message
      believability all had direct effects on alcohol consumption, and the interaction
      of sensation seeking and message believability impacted alcohol consumption,
      while the interaction of sensation seeking and perceived norms on alcohol
      consumption was marginally significant. Implications of these findings for the
      social norms marketing approach are discussed.

PMID- 21170786
TI  - Evaluation of a direct mailing campaign to increase physician awareness and
      utilization of a quitline fax referral service.
AB  - Research has shown that fax referral services play an important role in linking
      people who are ready to quit tobacco use with effective cessation support
      provided through telephone-based quitlines. While many states have implemented
      fax referral services to assist health care providers in connecting their
      patients to quitlines, few published studies delineate optimum ways to promote
      this service to providers, particularly the role of direct mail educational
      campaigns. This is one of the first studies to evaluate the effectiveness of a
      small-scale educational and promotional campaign designed to increase health care
      providers' awareness and utilization of a state tobacco cessation quitline fax
      referral service. The campaign included a direct mailing to 6,197 health care
      providers in North Carolina. The mailing consisted of a large tube, in the shape
      of cigarette, with enclosed fax referral promotional materials. An 8-month follow
      up survey was mailed to a 10% random sample of family physicians, pediatricians,
      dentists, and orthodontists who were sent the promotional tube mailing. Valid
      surveys were returned by 271 providers (response rate = 46%). Forty-four percent
      of respondents remembered receiving the tube mailing, and 40% reported
      familiarity with the fax referral service. While only 3.5% of respondents
      reported referring a patient to the quitline using the fax referral service in
      the previous 6 months, almost one-third reported an intention to use the fax
      referral service in the future. The pilot promotional campaign increased
      awareness of the fax referral service more than service utilization. While
      increased utilization of the service by health care providers appears promising,
      additional research is needed on how to maximize educational and promotional
      campaigns that influence clinician fax referral behaviors. The results of this
      study can help guide the development of future fax referral promotional campaigns
      to increase clinician access to and utilization of state quitlines.

PMID- 21170787
TI  - Physical activity related information sources predict physical activity behaviors
      in adults with type 2 diabetes.
AB  - Physical activity (PA) is a key management strategy for type 2 diabetes. Despite
      the known benefits, PA levels are low. Whether the low level of PA is related to
      lack of knowledge or support is not fully understood. This study was conducted to
      describe where and how often adults with type 2 diabetes receive and seek
      information related to PA and examine the relationships between the source and
      quality of PA information with PA behaviors. A series of questions related to the
      source and quality of PA information were added to a baseline survey distributed
      to the participants (N = 244) of the Canadian Aerobic and Resistance Training in
      Diabetes (CARED) study. Physicians and television were found to be the main
      sources of PA-related information. In our cross-sectional model, sources of PA
      related information other than that from health care professionals explained 14%
      (p = .05) and 16% (p < .05) of the variance for aerobic-based and resistance
      training behaviors and 22% (p < .01) and 15% (p < .05) for these behaviors in our
      longitudinal model. Physical activity (PA)-related information is widely
      available to adults with type 2 diabetes. Neither the quantity nor the quality of
      the PA information provided by health care professionals predicted PA behavior.
      These data provide further insight into the modes with which PA can be promoted
      to adults with type 2 diabetes.

PMID- 21170788
TI  - Comparison of online and face-to-face dissemination of a theory-based after
      school nutrition and physical activity training and curriculum.
AB  - This study was conducted to compare two different online delivery methods to
      train after school program leaders (ASPLs) to implement a nutrition and physical
      activity curriculum for children to each other and to a face-to-face (FTF)
      training model. A three-group design was used in which ASPLs from 12 states were
      randomized to either standard (n = 34) or an enhanced interaction (n = 31) online
      training, while a FTF group (n = 24) served as comparison. All ASPLs completed
      training and implemented curriculum lessons over 16 weeks from March to June
      2007. Weekly evaluations and pre and post-intervention questionnaires compared
      number of lessons implemented, subjective ratings of lesson success, and pre and
      post leader nutrition and physical activity knowledge. Multivariate linear
      regression analyses were used for among-group comparisons, paired Ttests for
      within-group knowledge change. Knowledge scores increased significantly (p <
      .001) within each group. All ASPLs fulfilled the goal of conducting at least 9
      lessons, and they rated 64% of lessons successful. After adjustment, knowledge
      change and success scores did not differ among groups. Implementation was
      significantly higher for FTF (+2.23 lessons, p = .013) than for enhanced
      interaction, but not for standard. Online training for ASPLs, such as the
      standard condition, are viable means of nutrition and physical activity education
      and program dissemination.

PMID- 21170790
TI  - Empowering low-income parents with skills to reduce excess pediatric emergency
      room and clinic visits through a tailored low literacy training intervention.
AB  - In this article, we evaluate the impact of a health literacy intervention to
      decrease emergency room and doctor's office visits for common childhood illness
      symptoms. Our education model trained low-income parents of young children (9,240
      families) at 55 Head Start sites on the use of a low-literacy health book to
      respond to common childhood illnesses. The overall strategic framework required
      each Head Start site to create a Health Improvement Project to plan, successfully
      train, monitor, and keep the momentum through a strong follow-up with families
      regarding their health care decisions. The study was conducted from 2003 to 2006.
      Each family was tracked for 3 months prior to the training using self-report, and
      for 6 months afterward. The average number of emergency room and doctor visits
      among parents decreased 58% and 41% respectively (p < .001). Further, work days
      missed by the primary caretaker per year decreased 42%, and school days missed
      per year decreased 29% (p < .001). During the health literacy intervention,
      emergency room and doctor visits reported among parents decreased, as well as the
      number of work days and school days missed per year. Significant cost savings for
      the health care system can be anticipated through thoughtful broad dissemination
      of this training model.

PMID- 21170789
TI  - Parental information seeking following a positive newborn screening for cystic
      fibrosis.
AB  - This investigation focused on the information-seeking behaviors of parents (N =
      38) whose newborn had received a positive screening result for cystic fibrosis.
      Roughly half of the participants actively sought information about their child's
      potential disease prior to the clinic visit. The most common sources of
      information were the Internet, pediatricians, and family physicians. Analysis of
      behavior during the clinic visit showed rates of question asking that were judged
      as low, but they were comparable to the results of other studies. It was observed
      that parents occasionally would collaborate in the production of a single
      question. More educated parents tended to produce such questions more frequently.
      Importantly, frequency of collaborative questions was positively correlated with
      enhanced knowledge of cystic fibrosis six weeks after the clinic visit and with
      apparent dissatisfaction with the counseling interaction.

PMID- 21170792
TI  - Immediate effect of visual and auditory feedback to control the running mechanics
      of well-trained athletes.
AB  - The correlation between mechanical factors of running and running economy as
      measured by metabolic cost is a subject of much interest in the study of
      locomotion. However, no change in running technique has been shown to result in
      an immediate improvement in running economy on an intra-individual basis. To
      evaluate the effect of a modified running technique, it is probably necessary
      that the individual trains with the new technique for a longer period using a
      feedback system to control the new kinematics. In this study, we examine the
      feasibility of using visual and auditory feedback to adapt running technique
      according to a simplistic model of the mechanical cost of running. The model
      considers only the mechanical work against gravity, which is the product of the
      magnitude of the vertical displacement of the runner's centre of mass and the
      step-frequency. In the experiments reported here, 18 trained runners, running at
      16 km . h(-1) on a treadmill, were given feedback on these parameters together
      with indicated target levels. In almost all cases, the runners were able to
      adjust their technique accordingly.

PMID- 21170793
TI  - Why peak power is higher at the end of steeper ramps: an explanation based on the
      "critical power" concept.
AB  - Experimental studies have consistently reported higher peak power outputs at the
      termination of steeper ramp exercises. One explanation can be deduced from oxygen
      uptake kinetics. This short communication offers an alternative explanation based
      on the "critical power" concept of human bioenergetics. Algebraic, calculus, and
      geometric aspects of this explanation are all detailed, and it is illustrated
      with data from a previous study.

PMID- 21170794
TI  - Effects of cold water immersion on the recovery of physical performance and
      muscle damage following a one-off soccer match.
AB  - The aim of this study was to assess the effects of a single session of cold or
      thermoneutral water immersion after a one-off match on muscular dysfunction and
      damage in soccer players. Twenty-male soccer players completed one match and were
      randomly divided into cryotherapy (10 min cold water immersion, 10 degrees C, n =
      10) and thermoneutral (10 min thermoneutral water immersion, 35 degrees C, n =
      10) groups. Muscle damage (creatine kinase, myoglobin), inflammation (C-reactive
      protein), neuromuscular function (jump and sprint abilities and maximal isometric
      quadriceps strength), and delayed-onset muscle soreness were evaluated before,
      within 30 min of the end, and 24 and 48 h after the match. After the match, the
      players in both groups showed increased plasma creatine kinase activity (30 min,
      24 h, 48 h), myoglobin (30 min) and C-reactive protein (30 min, 24 h)
      concentrations. Peak jump ability and maximal strength were decreased and delayed
      onset muscle soreness increased in both groups. However, differential alterations
      were observed between thermoneutral water and cold water immersion groups in
      creatine kinase (30 min, 24 h, 48 h), myoglobin (30 min), C-reactive protein (30
      min, 24 h, 48 h), quadriceps strength (24 h), and quadriceps (24 h), calf (24 h)
      and adductor (30 min) delayed-onset muscle soreness. The results suggest that
      cold water immersion immediately after a one-off soccer match reduces muscle
      damage and discomfort, possibly contributing to a faster recovery of
      neuromuscular function.

PMID- 21170795
TI  - Stress responses during aerobic exercise in relation to motivational dominance
      and state.
AB  - We examined the hypothesis that congruence between motivational dominance and
      state results in optimal psychological responses and performance during exercise.
      Twenty participants (10 telic dominant and 10 paratelic dominant) rated their
      stress at 5 min intervals as they cycled on an ergometer at gas exchange
      threshold for 30 min in both telic and paratelic state manipulated conditions.
      Participants then performed a test to exhaustion at a resistance equivalent to
      110% of VO(2max). The hypothesized interaction between condition and dominance
      was significant for internal tension stress, as paratelic dominants were more
      stressed than telic dominants when exercising in the telic state and telic
      dominants were more stressed than paratelic dominants when exercising in the
      paratelic state. Similarly, the condition * dominance interaction for internal
      stress discrepancy was significant, as paratelic dominants reported greater
      internal stress discrepancy exercising in the telic compared with the paratelic
      state. Findings are discussed in relation to the application of reversal theory
      for understanding stress responses during aerobic exercise.

PMID- 21170796
TI  - Quadriceps EMG muscle activation during accurate soccer instep kicking.
AB  - Six competitive soccer players were recruited to examine EMG activation in three
      quadriceps muscles during a kicking accuracy task. Participants performed three
      maximum instep place kicks of a stationary ball, 11 m perpendicular from the
      centre of the goal line towards targets (0.75 m(2)) in the four corners of the
      goal. Surface EMG of the vastus lateralis, vastus medialis, and rectus femoris of
      the kicking leg was normalized and averaged across all participants to compare
      between muscles, targets, and the phase of the kick. Although no significant
      difference were observed between muscles or kick phases, kicks to the right
      targets produced significantly greater muscle activity than those towards the
      left targets (P < 0.01). In addition, kicks towards the top right target
      demonstrated significantly greater muscle activity than towards the top and
      bottom left (P < 0.01). Under accurate soccer shooting conditions, kicks aimed to
      the top right corner of the goal demonstrated a higher level of quadriceps muscle
      activation than those towards the other corners.

PMID- 21170797
TI  - Discriminatory power of water polo game-related statistics at the 2008 Olympic
      Games.
AB  - The aims of this study were (1) to compare water polo game-related statistics by
      context (winning and losing teams) and sex (men and women), and (2) to identify
      characteristics discriminating the performances for each sex. The game-related
      statistics of the 64 matches (44 men's and 20 women's) played in the final phase
      of the Olympic Games held in Beijing in 2008 were analysed. Unpaired t-tests
      compared winners and losers and men and women, and confidence intervals and
      effect sizes of the differences were calculated. The results were subjected to a
      discriminant analysis to identify the differentiating game-related statistics of
      the winning and losing teams. The results showed the differences between winning
      and losing men's teams to be in both defence and offence, whereas in women's
      teams they were only in offence. In men's games, passing (assists), aggressive
      play (exclusions), centre position effectiveness (centre shots), and goalkeeper
      defence (goalkeeper-blocked 5-m shots) predominated, whereas in women's games the
      play was more dynamic (possessions). The variable that most discriminated
      performance in men was goalkeeper-blocked shots, and in women shooting
      effectiveness (shots). These results should help coaches when planning training
      and competition.

PMID- 21170798
TI  - Effects of antagonist pre-load on knee extensor isokinetic muscle performance.
AB  - The aim of this study was to evaluate and compare acute effects of a reciprocal
      action protocol and a super-set protocol on knee extensor performance during
      concentric isokinetic exercise. Fourteen men aged 29.4 +/- 6.1 years were tested
      on three different protocols, with 1 min of rest between sets: control (3 sets of
      10 isokinetic knee extension repetitions), reciprocal action protocol (3 sets of
      10 repetitions of reciprocal isokinetic concentric knee flexion and knee
      extension repetitions), and super-set protocol (3 sets of a combination of 10
      repetitions of knee flexion immediately followed by 10 repetitions of knee
      extension repetitions). Tests were performed at 60 degrees  . s(-1) and 180
      degrees  . s(-1), randomized across 3 days and separated by at least 72 h. There
      were no significant differences between protocols for peak torque at 60 degrees 
      . s(-1) or 180 degrees  . s(-1). Total work was significantly higher during the
      reciprocal action protocol compared with the super-set protocol at 60 degrees  .
      s(-1). There was a significant decline in peak torque (from 240.6 to 212.9 N . m)
      and total work (from 2294 to 1899 J) for the control condition at 60 degrees  .
      s(-1). Also, total work declined significantly across sets for the super-set
      protocol at 60 degrees  . s(-1) (from 2157 to 1707 J). Results indicate that a
      reciprocal action protocol provides torque maintenance during multiple sets of
      isokinetic training, both at slow and high velocities.

PMID- 21170799
TI  - The impact of different types of physical activity on total and regional bone
      mineral density in young Brazilian athletes.
AB  - Bone turnover is affected by exercise throughout the lifespan, especially during
      childhood and adolescence. The objective of this study was to investigate the
      impact of different sports on total and regional bone mineral density in male
      Brazilian adolescent athletes. Forty-six adolescents aged 10-18 years
      participated in the study: 12 swimmers, 10 tennis players, 10 soccer players, and
      14 sedentary individuals. The athletes had engaged in physical activities for
      more than 10 h per week in the previous 6 months. Bone mineral density of the
      lumbar spine (L1-L4), left proximal femur region, and whole body was evaluated by
      dual-energy X-ray absorptiometry. Results showed higher mean values in the
      proximal femur region of tennis and soccer players (1.02 +/- 0.18; 0.96 +/- 0.16,
      respectively) than swimmers and controls (0.91 +/- 0.14 and 0.87 +/- 0.06,
      respectively) (P < 0.05). In relation to the impact of sporting activities based
      on bone age determination, we observed significant differences in bone mineral
      density at all evaluated sites at the end of puberty (16-18 years) compared with
      10-12 years, with increases of 78% in the lumbar spine, 47% in the proximal
      femur, and 38% in the whole body.

PMID- 21170800
TI  - Effect of tennis racket parameters on a simulated groundstroke.
AB  - Composite materials have given manufacturers the freedom to develop a broad range
      of tennis rackets, allowing them to change key parameters such as the structural
      stiffness, mass, and position of the balance point. The aim of this research was
      to determine how changing these parameters could affect ball resultant rebound
      velocity and spin for a simulated groundstroke. A finite element model of a
      freely suspended racket and strings was used to determine the effect of racket
      parameters for oblique spinning impacts at a range of locations on the stringbed.
      The finite element simulations were conducted in the laboratory frame of
      reference, where the ball is projected onto an initially stationary racket. The
      mean rebound velocity of the ball was 9% higher for a structurally stiff racket,
      37% higher for a heavy racket, and 32% higher for a head-heavy racket. In
      addition, the mean rebound topspin of the ball was 23% higher for a heavy racket
      and 21% higher for a head-heavy racket. Therefore, in relation to a groundstroke
      with an impact location away from the node, the rebound velocity of the ball is
      likely to increase with the structural stiffness of a racket. The effect of
      changing the mass and position of the balance point is more complex, as it is
      dependent on the relationship between the transverse moment of inertia and
      maximum pre-impact swing velocity.

PMID- 21170801
TI  - Ground reaction forces and knee mechanics in the weight acceptance phase of a
      dance leap take-off and landing.
AB  - Aesthetic constraints allow dancers fewer technique modifications than other
      athletes to negotiate the demands of leaping. We examined vertical ground
      reaction force and knee mechanics during a saut de chat performed by healthy
      dancers. It was hypothesized that vertical ground reaction force during landing
      would exceed that of take-off, resulting in greater knee extensor moments and
      greater knee angular stiffness. Twelve dancers (six males, six females; age 18.9
      +/- 1.2 years, mass 59.2 +/- 9.5 kg, height 1.68 +/- 0.08 m, dance training 8.9
      +/- 5.1 years) with no history of low back pain or lower extremity pathology
      participated in the study. Saut de chat data were captured using an eight-camera
      Vicon system and AMTI force platforms. Peak ground reaction force was 26% greater
      during the landing phase, but did not result in increased peak knee extensor
      moments. Taking into account the 67% greater knee angular displacement during
      landing, this resulted in less knee angular stiffness during landing. In
      conclusion, landing was accomplished with less knee angular stiffness despite the
      greater peak ground reaction force. A link between decreased joint angular
      stiffness and increased soft tissue injury risk has been proposed elsewhere;
      therefore, landing from a saut de chat may be more injurious to the knee soft
      tissue than take-off.

PMID- 21170802
TI  - Taekwondo training and fitness in female adolescents.
AB  - In this study, we determined the specificity of a low frequency taekwondo
      training programme on physical fitness levels in adolescent females who receive
      limited physical education instruction (i.e. 2 days per week). Major components
      of physical fitness assessed were: skeletal muscle fitness (hand grip strength,
      bent arm hang, standing long jump, and isokinetic strength), flexibility (sit-and
      reach test), speed and agility (10 * 5-m shuttle run), and cardiovascular fitness
      (VO(2max) and 20-m shuttle run). Changes in body composition were also assessed
      (dual X-ray absorptiometry, DXA). Participants were divided into two groups, a
      taekwondo training group (n = 21), which trained 50 min a day, 2 days per week
      for 12 weeks, and a control group (n = 10). Taekwondo training improved
      isokinetic strength, standing long jump, and sit-and-reach performance. Body fat
      mass and percent body fat were reduced. No changes in grip strength, bent arm
      hang time, speed and agility, or cardiorespiratory fitness were observed. Results
      indicate that low frequency taekwondo training in adolescent females produces
      beneficial changes in skeletal muscle fitness, flexibility, and body composition
      in a relatively short period of time. Consequently, this specific type of
      training can be useful to female adolescents in structured school environments
      where physical education classes are limited and there is little free time for
      physical activity.

PMID- 21170803
TI  - One-arm maximal strength training improves work economy and endurance capacity
      but not skeletal muscle blood flow.
AB  - Maximal strength training with a focus on maximal mobilization of force in the
      concentric phase improves endurance performance that employs a large muscle mass.
      However, this has not been studied during work with a small muscle mass, which
      does not challenge convective oxygen supply. We therefore randomized 23 adult
      females with no arm-training history to either one-arm maximal strength training
      or a control group. The training group performed five sets of five repetitions of
      dynamic arm curls against a near-maximal load, 3 days a week for 8 weeks. This
      training increased maximal strength by 75% and improved rate of force development
      during both strength and endurance exercise, suggesting that each arm curl became
      more efficient. This coincided with a 17-18% reduction in oxygen cost at
      standardized submaximal workloads (work economy), and a 21% higher peak oxygen
      uptake and 30% higher peak load during maximal arm endurance exercise. Blood flow
      assessed by Doppler ultrasound in the axillary artery supplying the working
      biceps brachii and brachialis muscles could not explain the training-induced
      adaptations. These data suggest that maximal strength training improved work
      economy and endurance performance in the skeletal muscle, and that these effects
      are independent of convective oxygen supply.

PMID- 21170804
TI  - Eccentric exercise-induced muscle damage dissociates the lactate and gas exchange
      thresholds.
AB  - We tested the hypothesis that exercise-induced muscle damage would increase the
      ventilatory (V(E)) response to incremental/ramp cycle exercise (lower the gas
      exchange threshold) without altering the blood lactate profile, thereby
      dissociating the gas exchange and lactate thresholds. Ten physically active men
      completed maximal incremental cycle tests before (pre) and 48 h after (post)
      performing eccentric exercise comprising 100 squats. Pulmonary gas exchange was
      measured breath-by-breath and fingertip blood sampled at 1-min intervals for
      determination of blood lactate concentration. The gas exchange threshold occurred
      at a lower work rate (pre: 136 +/- 27 W; post: 105 +/- 19 W; P < 0.05) and oxygen
      uptake (VO(2)) (pre: 1.58 +/- 0.26 litres . min(-1); post: 1.41 +/- 0.14 litres .
      min(-1); P < 0.05) after eccentric exercise. However, the lactate threshold
      occurred at a similar work rate (pre: 161 +/- 19 W; post: 158 +/- 22 W; P > 0.05)
      and VO(2) (pre: 1.90 +/- 0.20 litres . min(-1); post: 1.88 +/- 0.15 litres . min(
      1); P > 0.05) after eccentric exercise. These findings demonstrate that exercise
      induced muscle damage dissociates the V(E) response to incremental/ramp exercise
      from the blood lactate response, indicating that V(E) may be controlled by
      additional or altered neurogenic stimuli following eccentric exercise. Thus, due
      consideration of prior eccentric exercise should be made when using the gas
      exchange threshold to provide a non-invasive estimation of the lactate threshold.

PMID- 21170805
TI  - The effect of patellar taping on EMG activity of vasti muscles during squatting
      in individuals with patellofemoral pain syndrome.
AB  - Although patellar taping has been shown to reduce pain in participants with
      patellofemoral pain syndrome, the mechanisms of pain reduction have not
      completely been established following its application. The purpose of this study
      was to evaluate EMG activity of vastus medialis and vastus lateralis following
      the application of patellar taping during a functional single leg squat. Both
      vastus medialis obliquus-vastus lateralis onset and vastus medialis
      obliquus/vastus lateralis amplitude of 18 participants with patellofemoral pain
      syndrome and 18 healthy participants as controls were measured using an EMG unit.
      This procedure was performed on the affected knee of participants with
      patellofemoral pain syndrome, before, during, and after patellar taping during
      unilateral squatting. The same procedure was also performed on the unaffected
      knees of both groups. The mean values of vastus medialis obliquus-vastus
      lateralis onset prior to taping (2.54 ms, s = 4.35) were decreased significantly
      following an immediate application of tape (-3.22 ms, s = 3.45) and after a
      prolonged period of taping (-6.00 ms, s = 3.40 s) (P < 0.05). There was also a
      significant difference between the mean values of vastus medialis obliquus-vastus
      lateralis onset among controls (-2.03 ms, s = 6.04) and participants with
      patellofemoral pain syndrome prior to taping (P < 0.05). However, there were no
      significant difference between the ranked values of vastus medialis
      obliquus/vastus lateralis amplitude of the affected and unaffected knees of
      participants with patellofemoral pain syndrome and controls during different
      conditions of taping (P > 0.05). Decreased values of vastus medialis obliquus
      vastus lateralis onset may contribute to patellar realignment and explain the
      mechanism of pain reduction following patellar taping in participants with
      patellofemoral pain syndrome.

PMID- 21170806
TI  - Determination of muscle activity during running at reduced body weight.
AB  - The aim of this study was to investigate how lower extremity muscles are
      influenced by body weight support during running at different speeds. Nine
      participants (age 24 +/- 2 years, height 1.75 +/- 0.12 m, mass 73.5 +/- 15.7 kg)
      ran at 100%, 115%, and 125% of preferred speed at 100%, 90%, 80%, 70%, and 60% of
      body weight on a treadmill that provided body weight support. Preferred speed was
      self-selected by each participant and represented a speed that he or she could
      sustain if going for a 30 min run. Electromyography (EMG) data were recorded
      (1000 Hz, 1 min) from the bicep femoris, rectus femoris, tibialis anterior, and
      gastrocnemius for each condition together with knee angle (electrogoniometer).
      Average and root mean square EMG were calculated across 30 s. Muscle patterns
      were determined by smoothing (low-pass filter, 4 Hz) and extracting patterns for
      49 cycles defined by consecutive maximum knee flexion angles. Repeated-measures
      analyses of variance were used to compare average and root mean square across
      body weight and speeds. Correlations were computed between the 100% speed/100%
      body weight condition and all other conditions per muscle. There was no
      interaction between body weight and speed (P > 0.05). Average and root mean
      square decreased as body weight decreased for all muscles (P < 0.05) and
      increased across speeds for all muscles (P < 0.05). Correlations for all muscles
      between conditions were high (range: 0.921-0.999). Although a percent reduction
      in body weight did not lead to the same reduction in muscle activity, it was
      clear that reducing body weight leads to a reduction in muscle activity with no
      changes in muscle activity patterns.

PMID- 21170808
TI  - Renal effects of exposure to natural and depleted uranium: a review of the
      epidemiologic and experimental data.
AB  - Elevated levels of naturally occurring uranium in groundwater have been found in
      small geographic areas throughout the world. Relevant research was reviewed
      pertaining to natural and depleted uranium (DU) exposure and nephrotoxicity,
      including epidemiologic community-based and occupational studies, studies of Gulf
      War veterans exposed to DU, and experimental studies in animals. Occupational
      cohort studies do not provide evidence of an increased risk of kidney-related
      mortality among uranium-exposed workers. However, occupational and community
      based studies of populations chronically exposed to elevated drinking-water
      concentrations of uranium provide some evidence of adverse renal effects, as
      assessed by biomarkers of proximal tubule damage such as urinary levels of
      glucose, calcium, and various low-molecular-weight proteins. Indications of
      proximal tubule effects, as evidenced by increased urinary beta(2)-microglobulin
      and retinol binding protein levels, were also seen in the most recent follow-up
      surveillance study of Gulf War veterans exposed to DU. The reported beta(2)
      microglobulin levels in these studies were generally considered to be within
      normal limits, but the long-term implications of the observed variation in these
      levels are not established. The kidney was observed to be a target of uranium
      toxicity following oral and implantation exposure routes in several animal
      species. The interpretation and importance of the observed changes in biomarkers
      of proximal tubule function are important questions that indicate the need for
      additional clinical, epidemiological, and experimental research.

PMID- 21170807
TI  - Metabolism, genotoxicity, and carcinogenicity of comfrey.
AB  - Comfrey has been consumed by humans as a vegetable and a tea and used as an
      herbal medicine for more than 2000 years. Comfrey, however, produces
      hepatotoxicity in livestock and humans and carcinogenicity in experimental
      animals. Comfrey contains as many as 14 pyrrolizidine alkaloids (PA), including 7
      acetylintermedine, 7-acetyllycopsamine, echimidine, intermedine, lasiocarpine,
      lycopsamine, myoscorpine, symlandine, symphytine, and symviridine. The mechanisms
      underlying comfrey-induced genotoxicity and carcinogenicity are still not fully
      understood. The available evidence suggests that the active metabolites of PA in
      comfrey interact with DNA in liver endothelial cells and hepatocytes, resulting
      in DNA damage, mutation induction, and cancer development. Genotoxicities
      attributed to comfrey and riddelliine (a representative genotoxic PA and a proven
      rodent mutagen and carcinogen) are discussed in this review. Both of these
      compounds induced similar profiles of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H
      pyrrolizine (DHP)-derived DNA adducts and similar mutation spectra. Further, the
      two agents share common mechanisms of drug metabolism and carcinogenesis.
      Overall, comfrey is mutagenic in liver, and PA contained in comfrey appear to be
      responsible for comfrey-induced toxicity and tumor induction.

PMID- 21170809
TI  - An exposure-response curve for copper excess and deficiency.
AB  - There is a need to define exposure-response curves for both Cu excess and
      deficiency to assist in determining the acceptable range of oral intake. A
      comprehensive database has been developed where different health outcomes from
      elevated and deficient Cu intakes were assigned ordinal severity scores to create
      common measures of response. A generalized linear model for ordinal data was used
      to estimate the probability of response associated with dose, duration and
      severity. The model can account for differences in animal species, the exposure
      medium (drinking water and feed), age, sex, and solubility. Using this model, an
      optimal intake level of 2.6 mg Cu/d was determined. This value is higher than the
      current U.S. recommended dietary intake (RDI; 0.9 mg/d) that protects against
      toxicity from Cu deficiency. It is also lower than the current tolerable upper
      intake level (UL; 10 mg/d) that protects against toxicity from Cu excess.
      Compared to traditional risk assessment approaches, categorical regression can
      provide risk managers with more information, including a range of intake levels
      associated with different levels of severity and probability of response. To
      weigh the relative harms of deficiency and excess, it is important that the
      results be interpreted along with the available information on the nature of the
      responses that were assigned to each severity score.

PMID- 21170810
TI  - North American osprey populations and contaminants: historic and contemporary
      perspectives.
AB  - Osprey (Pandion haliaetus) populations were adversely affected by DDT and perhaps
      other contaminants in the United States and elsewhere. Reduced productivity,
      eggshell thinning, and high DDE concentrations in eggs were the signs associated
      with declining osprey populations in the 1950s, 1960s, and 1970s. The species was
      one of the first studied on a large scale to bring contaminant issues into focus.
      Although few quantitative population data were available prior to the 1960s, many
      osprey populations in North America were studied during the 1960s and 1970s with
      much learned about basic life history and biology. This article reviews the
      historical and current effects of contaminants on regional osprey populations.
      Breeding populations in many regions of North America showed post-DDT-era (1972)
      population increases of varying magnitudes, with many populations now appearing
      to stabilize at much higher numbers than initially reported in the 1970s and
      1980s. However, the magnitude of regional population increases in the United
      States between 1981 (first Nationwide Survey, ~8,000 pairs), when some recovery
      had already occurred, 1994 (second survey, ~14,200), and 2001 (third survey,
      ~16,000-19,000), or any other years, is likely not a simple response to the
      release from earlier contaminant effects, but a response to multi-factorial
      effects. This indirect "contaminant effects" measurement comparing changes (i.e.,
      recovery) in post-DDT-era population numbers over time is probably confounded by
      changing human attitudes toward birds of prey (shooting, destroying nests, etc.),
      changing habitats, changing fish populations, and perhaps competition from other
      species. The species' adaptation to newly created reservoirs and its increasing
      use of artificial nesting structures (power poles, nesting platforms, cell
      towers, channel markers, offshore duck blinds, etc.) are two important factors.
      The timing of the initial use of artificial nesting structures, which replaced
      declining numbers of suitable trees at many locations, varied regionally (much
      later in the western United States and Mexico). Because of the increasing use of
      artificial nesting structures, there may be more ospreys nesting in North America
      now than ever before. Now, with the impact of most legacy organic contaminants
      (DDT, other organochlorine [OC] pesticides, polychlorinated biphenyls [PCB],
      polychlorinated dibenzo-p-dioxins [PCDD], polychlorinated dibenzofurans (PCDF])
      greatly reduced or eliminated, and some osprey populations showing evidence of
      stabilizing, the species was proposed as a Worldwide Sentinel Species for
      evaluating emerging contaminants. Several emerging contaminants are already being
      studied, such as polybrominated diphenyl ethers (PBDE) and perfluorinated acids
      and sulfonate compounds (PFC). The many advantages for continued contaminant
      investigations using the osprey include a good understanding of its biology and
      ecology, its known distribution and abundance, and its ability to habituate to
      humans and their activities, which permits nesting in some of the potentially
      most contaminated environments. It is a top predator in most ecosystems, and its
      nests are relatively easy to locate and study with little researcher impact on
      reproductive success.

PMID- 21170811
TI  - A heat-stable extract from Mucuna stimulates the differentiation of bone marrow
      cells into dendritic cells and induces apoptosis in cancer cells.
AB  - Pine cone extract is known to induce differentiation of human mononuclear cells
      into dendritic cells (DCs) and also to induce apoptosis in human cancer cells. In
      the present study, we screened edible plants that contain components with
      biological activities similar to or more potent than those of pine cone extract.
      We found that Mucuna (Mucuna pruviens var. utilis) contains a DC
      differentiation/maturation-inducing activity and a component that induces
      apoptosis in human cancer cell lines. Mucuna extract specifically stimulated
      differentiation of BM cells to immature DCs. Marked production of IL-6 was
      observed by sequential treatment with at least 10 MUg/mL of Mucuna extract
      followed by LPS. The sequential treatment with Mucuna extract followed by LPS
      produced a much higher ratio of IL-12 to IL-6 and a lower ratio of TNF-alpha to
      IL-6 than that obtained by sequential treatment with a medicinal mushroom
      Phellinus linteus extract and then LPS. The DC differentiation/maturation
      activity and the component inducing apoptosis in cancer cells were separable by
      column chromatography.

PMID- 21170812
TI  - Effects of non-digestible carbohydrates on the growth of estrogen-dependent human
      breast cancer (MCF-7) tumors implanted in ovariectomized athymic mice.
AB  - Non-digestible carbohydrates (NDC(4)) have been used as a low-calorie sweetener
      and prebiotics that stimulate the growth of certain intestinal bacteria that
      support healthy colon conditions. In this study, we examined the dietary effect
      of commercially available NDCs on estrogen receptor positive (ER+) human breast
      cancer. We conducted a feeding study of fructooligosaccharides (FOSs), Fibersol 2
      (F2; digestion resistant maltodextrin), Hi-Maize (HM; high amylose cornstarch),
      and Frutafit (FF; a range of powdered inulins) (5% in diet, w/w) to evaluate
      their effects on the growth of ER(+) human breast cancer (MCF-7) tumors in the
      presence of 17beta-estradiol (E(2)) using an athymic xenograft model. F2, HM, and
      FOSs supplementation significantly reduced E(2)-stimulated MCF-7 tumor growth by
      inhibiting cellular proliferation (Ki-67) and increasing apoptosis (M30) in
      tumors. F2, HM, and FOSs treatments also lowered serum E(2) level and reduced
      uterine weight compared to the control diet. NDCs treatments downregulated
      relative mRNA expression of the E(2)-responsive gene markers pS2, bcl2, bcl-xL,
      and cyclin D1 in MCF-7 tumors. In conclusion, the NDC intake may have a
      protective effect against ER(+) tumors by inhibiting cellular proliferation and
      increasing apoptosis.

PMID- 21170813
TI  - Diet and expression of estrogen alpha and progesterone receptors in malignant
      mammary tissue.
AB  - Estrogen receptor (ER) and/or progesterone receptor (PR) expression has been
      associated with more favorable breast cancer prognosis. Results on the
      differential association of diet with ER and/or PR positive and negative tumors
      have been inconclusive. In a large case-control study conducted in Athens,
      Greece, we investigated whether diet is associated with the expression of ER
      alpha or PR in mammary tumors of 421 women with histologically confirmed breast
      cancer. Diet was assessed through an extensive food frequency questionnaire and
      results were analyzed using multiple logistic regression. After controlling for
      non-nutritional variables and mutually adjusting for energy-generating nutrients
      and ethanol, carbohydrate intake was inversely associated with ER-alpha (P =
      0.04) and PR (P = 0.10) expression. The odds ratios (OR) per one standard
      deviation increment were 0.69 with 95% confidence interval (95% CI) 0.48-0.98 for
      ER-alpha and 0.72 (95% CI 0.49-1.07) for PR expression. No consistent or
      statistically significant associations were noted for any of the other energy
      generating nutrients or food groups examined. Although in these data no strong
      relations of qualitative aspects of diet with hormone receptor expression in
      breast cancer tumors were evident, the inverse association of carbohydrate intake
      with ER-alpha, and perhaps PR, expression merits further study in future
      investigations.

PMID- 21170814
TI  - Factors associated with delays to diagnosis and treatment of breast cancer in
      women in a Louisiana urban safety net hospital.
AB  - Only lung cancer surpasses breast cancer as a cause of death from cancer.
      However, the burden of cancer is not borne equally across racial and ethnic
      groups. In the United States, African American women have significantly higher
      mortality rates from breast cancer than white women. Delayed follow-up of breast
      abnormalities and delays from diagnosis to treatment may contribute to higher
      mortality. This study examined factors associated with delays to diagnosis and
      treatment of breast cancer in a group of white and African American women.
      Identified from tumor registry records were 247 women with pathology-confirmed
      first primary in situ and invasive breast carcinomas with no known previous
      cancer diagnosis. Factors associated with delays from provider recognition of
      abnormality to breast cancer diagnosis (diagnostic delays) and from diagnosis to
      treatment (treatment delays) were determined using chi-square tests and logistic
      regression. Factors that were considered included age, race, stage of disease at
      diagnosis, tumor size, type of abnormality, type of medical service at
      presentation, and prior mammogram within the past two years. The proportion of
      women experiencing diagnostic delays was high, with more African American women
      experiencing delays than white women (34% versus 17%, respectively). African
      American and white women did not differ in distribution of stage of cancer at
      diagnosis. Significantly smaller tumor sizes were found in women experiencing
      diagnostic delays compared to those not experiencing delays. Conversely, women
      experiencing treatment delays were significantly older and had larger tumor sizes
      compared to those not experiencing delays. More African American women
      experienced delays in diagnosis; however these delays did not appear to affect
      outcomes. Older age as a significant factor in treatment delays suggests that
      comorbidities as well as other possible barriers to treatment warrant further
      investigation in older women. The reasons for racial disparities in breast cancer
      outcomes remain and call for further study.

PMID- 21170816
TI  - Working sensitively with child sexual abuse survivors: what female child sexual
      abuse survivors want from health professionals.
AB  - Adult survivors of child sexual abuse are high users of health and mental health
      services. Health professionals are well placed to improve health outcomes for
      them by delivering positive interventions post-abuse. The current study explored
      female child sexual abuse survivors' opinions on how health professionals could
      work better with child sexual abuse survivors. Sixty-one women, from 22-65 years
      old, who had been sexually abused before the age of 16 years, completed postal
      questionnaires in late 2004. A model was developed to guide the development of
      knowledge, skills, and practices for working more sensitively with child sexual
      abuse survivors. The model consisted of six chronological training steps: (1)
      knowledge on effects of child sexual abuse; (2) establishing the relationship
      with child sexual abuse survivors; (3) asking about child sexual abuse; (4)
      responding to disclosure; (5) sensitive provision of medical examinations; and
      (6) follow-up post examination. A systematic approach to training is proposed to
      assist with improving delivery of services sensitive to child sexual abuse
      survivor needs.

PMID- 21170815
TI  - Health and health care disparities among homeless women.
AB  - While disparities in health and health care between vulnerable (e.g., minorities,
      low-income) and majority populations are well documented, less is known about
      disparities within these special populations that are large and diverse. Such
      knowledge is essential to determine the neediest within these generally needy
      populations, and to plan interventions to reduce their health and health care
      disparities. With data from 1,331 women residing in Los Angeles County
      California, in one of the largest, most comprehensive studies of the health of
      homeless women to date, this study examined the health and health care
      disparities among homeless African American, Latina, and white women. This study
      further explored if race/ethnicity and other factors that predispose homeless
      women to poor health, or enable them to obtain better health care, were
      associated with their unmet need for medical care. The study found that white,
      non-Latina women were more likely to report unmet need than African Americans and
      Latinas, and women suffering from drug abuse, violence, or depression were most
      in need of care. These findings should be considered in targeting and addressing
      the special needs of homeless women of different racial/ethnic groups.

PMID- 21170817
TI  - Early pregnancy blood lead and spontaneous abortion.
AB  - Although evidence tends to suggest that high levels of lead exposure increase the
      risk of spontaneous abortion, we do not yet know whether moderate- to low-level
      exposure elevates risk. Among 351 women (aged 16 to 35 years, with single
      pregnancies) who were registered for a longitudinal study, 15 (4.3%) women
      experienced spontaneous abortion after the 12th week of gestation and before the
      20th week. We collected participants' blood samples during the first trimester of
      pregnancy (8-12 weeks) for lead measurement by inductively coupled plasma-mass
      spectrometry. Mean +/- standard deviation of blood lead was 3.8 +/- 2.0 MUg/dl
      (range 1.0-20.5 MUg/dl) with a geometric mean of 3.5 MUg/dl. Mean blood lead
      concentrations did not differ significantly between spontaneous abortion cases
      and ongoing pregnancies (3.51 +/- 1.42 and 3.83 +/- 1.99 MUg/dl, respectively).
      The findings suggest that in apparently healthy women, low blood lead levels
      (mean < 5 MUg/dl) measured in early pregnancy may not be a risk factor for
      spontaneous abortion.

PMID- 21170818
TI  - Family and peer influences on sexual behavior among female college students in
      Wuhan, China.
AB  - The prevalence of sexually transmitted infections in China has increased
      dramatically over the last 20 years, and heterosexual transmission is rapidly
      becoming the primary route of HIV transmission. Despite this growing epidemic,
      little is known about the correlates of sexual behavior in young Chinese women.
      The objective of this study was to assess family and peer factors related to
      sexual behavior in Chinese female college students. Anonymously completed
      questionnaires were received from 4,769 unmarried female college students,
      recruited using randomized cluster sampling by type of university and students'
      major and grade. Items captured socio-demographic, family, and peer factors. To
      examine factors associated with sexual behavior, multiple logistic regression was
      used, yielding odds ratios and 95% confidence intervals. Over 18% of female
      students participating reported ever having sexual intercourse, of whom 31.52%
      had their first sexual intercourse at the age of 18 or younger with more than 50%
      at an age less than 20 years. Several socio-demographic, family, and peer factors
      were associated with ever having intercourse. Those more likely to engage in
      premarital sex were older; majored in art; were from one-child, richer and/or
      divorced families; had a mother with university or above education; had parents
      with a strict disciplinary style; had middle-school close friends falling in
      love; and had current close friends living with boyfriends. Interventions to
      protect young women from sexually transmitted diseases need to target early sex
      education and address peer and parents influences.

PMID- 21170820
TI  - [Peace on earth].

PMID- 21170819
TI  - Correlates of television viewing among African American and Caucasian women.
AB  - This study explores the associations between time spent watching television and
      physical activity, selected eating behaviors, and quality of life variables among
      189 African American and Caucasian women aged 18-60 years. Data were collected
      via a cross-sectional, random-digit-dialed telephone survey. Seventy-two percent
      and 46% of women reported to "always, often, or sometimes" eating or overeating
      while watching television, respectively. Significant associations with television
      time per week included: eating meals or snacks while watching television, number
      of days per month feeling depressed, number of days per month feeling anxious,
      self-rated health, and BMI. Results contribute to recent studies finding
      associations between television viewing, body mass index, and health; and suggest
      potential points for intervention.

PMID- 21170822
TI  - ["15 questions about..."].

PMID- 21170821
TI  - [Personal contextual factors of the ICF draft from the Working Group "ICF" of
      Specialty Group II of the Geman Society for Social Medicine and Prevention].
AB  - Personal contextual factors play an essential part in the ICF model in relation
      to patient-centred care. It is generally assumed that their classification must
      refer to the country-specific social and cultural setting and its particular
      linguistic terms. Therefore personal factors are not classified as yet by the WHO
      for general use. In Germany in 2006 a group of experts working on the medical
      advisory board of statutory health insurance published a proposal for a
      systematic classification of relevant personal factors to describe the background
      of an individual's life and living. This classification was now further analysed
      and thoroughly revised by a more comprehensive group of German specialists
      working in different health care insurances and institutions, authorised by the
      German Society for Social Medicine and Prevention (DGSMP), supported by German
      speaking Swiss ICF specialists. This classification is published as work in
      progress intending to broaden and prepare the process of discussion for a
      consensus conference to be held in Germany in 2011.

PMID- 21170823
TI  - Neuroblastoma imaging.
AB  - Neuroblastoma is an embryonic tumor of the sympathetic nervous system which
      represents one of the most common malignancies in early childhood. Its clinical
      and biological behavior show a remarkable heterogeneity, ranging from spontaneous
      regression to inexorable progression with a fatal outcome. This review summarizes
      the clinical risk stratification and treatment options. An extensive overview of
      the role of imaging during the course of the disease and typical imaging findings
      in all imaging modalities are demonstrated.

PMID- 21170824
TI  - Ex-vivo human lung tumor model: use for temperature measurements during thermal
      ablation of NSCLC.
AB  - PURPOSE: In the present study we used an ex-vivo human lung cancer model to
      compare temperature diffusion during thermal ablation using one laser fiber to
      that of a two-fiber approach. Furthermore, we examined whether there was a
      difference between temperature diffusion in normal lung tissue and tumor tissue
      during laser ablation. MATERIALS AND METHODS: 48 resected lung specimens
      containing non-small cell lung cancer were connected to a perfusion/ventilation
      apparatus and treated with 1 (22 specimens, group 1) or, in a second experiment,
      with 1 (13 specimens, group 2) or 2 (13 specimens, group 3) laser fibers. During
      tumor ablation, temperatures were measured interstitially every 5 sec. Laser
      ablation was followed by the taking of samples of 13 specimens for histological
      examination. For comparison we performed laser ablation in 7 specimens with
      normal lung tissue. RESULTS: Laser treatment and temperature control were
      technically feasible in all samples. Thirty min after starting laser ablation
      with 1 fiber, a temperature of 61 +/- 17  degrees C was achieved in group 1 at a
      distance of 10 mm from the laser fiber and a temperature of 74 +/- 11  degrees C
      was achieved in group 2 (p = 0.1). In the middle between two active laser fibers
      placed 20 mm apart, a temperature of 93 +/- 7  degrees C was achieved. The
      temperature reached in normal lung tissue after 20 min of laser ablation was 77
      +/- 15  degrees C at a distance of 10 mm from the laser fiber. CONCLUSION: The ex
      vivo model allowed performance of laser-induced thermal ablation in the perfused
      and ventilated lung. The use of two laser fibers increases the achieved
      temperatures significantly (p < 0.05). Temperatures reached in normal lung tissue
      were as high as in tumor tissue (p = 0.24).

PMID- 21170825
TI  - Oxytocin antagonists for the management of preterm birth: a review.
AB  - Preterm birth, the leading cause of neonatal morbidity and mortality, is
      estimated at incidence of 12.7% of all births, which has not decreased over the
      last four decades despite intensive antenatal care programs aimed at high-risk
      groups, the widespread use of tocolytics, and a series of other preventive and
      therapeutic interventions. Oxytocin antagonists, namely atosiban, represent an
      appealing choice that seems to be effective with apparently fewer side effects
      than the traditional tocolytics. This article reviews the available literature on
      the pharmacokinetics, mode of administration, and clinical utility of oxytocin
      antagonists for acute and maintenance tocolysis with special emphasis on its
      safety profile.

PMID- 21170826
TI  - Impact of land-based neonatal transport on outcomes in transient tachypnea of the
      newborn.
AB  - We sought to determine the effect of neonatal transport on the incidence of
      adverse events of transient tachypnea of the newborn (TTN) in term neonates. A
      retrospective study was performed of neonates who had TTN and were admitted to
      Neonatal Intensive Care Unit (NICU) of Sami Ulus Maternity, Children's Education
      and Research Hospital by land-based transport. Data from 208 newborns with TTN
      were evaluated, and clinical and laboratory findings were compared between
      patients who were transported from within the city (group 1) or from outside of
      the city (group 2). In the present study, long-distance land-based neonatal
      transport increased the adverse effects of TTN in newborns. Arterial blood gas
      parameters of the neonates in both groups before transport were similar, and
      these parameters and Downes' scores were comparable in both groups, implying that
      patients from outside the city had greater respiratory insufficiency than those
      from inside the city at admission to NICU. Respiratory support in the NICU and
      pulmonary air leak syndrome ratios were found to be significantly higher in the
      group from outside the city. Long-distance land-based transport in neonates with
      TTN increases the severity of illness. Furthermore, adverse events and the
      outcome of such infants depend on the effectiveness of the neonatal transport
      system.

PMID- 21170827
TI  - A randomized, double-masked trial of prophylactic indomethacin tocolysis versus
      placebo in women with premature rupture of membranes.
AB  - Preterm premature rupture of membranes (PPROM) complicates 3% of pregnancies and
      frequently results in preterm birth, often within 48 hours of membrane rupture.
      Our objective was to determine if subjects with PPROM between 24 and 31 (6)/ (7)
      weeks' gestation benefit from a 48-hour course of prophylactic indomethacin
      tocolysis. This was a double-masked randomized controlled trial. Subjects with
      PPROM between 24 and 31 (6)/ (7) weeks' gestation were randomized to receive
      indomethacin or placebo for 48 hours in addition to corticosteroids and latency
      antibiotics. The primary outcome of the study was delivery within 48 hours.
      Maternal and neonatal outcomes were also compared. This study was concluded
      prematurely due to slow accrual after a total of 50 subjects were enrolled. A
      total of 23/25 (92%) subjects in the indomethacin group remained pregnant beyond
      48 hours compared with 20/22 (90.9%) in the placebo group (relative risk, 1.01;
      95% confidence interval, 0.84 to 1.21). The latency period medians and
      interquartile ranges were similar between the two groups [indomethacin 193 (92 to
      376.5) hours versus placebo 199 (77.5 to 459) hours, P = 0.91], and no
      differences were noted in any maternal or neonatal secondary outcomes. This
      limited study demonstrates no benefit with the use of prophylactic indomethacin
      tocolysis for women with PPROM.

PMID- 21170828
TI  - Malignant progression of anaplastic supratentorial ganglioglioma into
      glioblastoma multiforme in a patient with turner syndrome.

PMID- 21170829
TI  - Transnasal endoscopy to facilitate nasobiliary tube placement: a simple and safe
      technique to avoid injury to the endoscopist.

PMID- 21170830
TI  - Migration of a percutaneous endoscopic gastrostomy tube into the transverse
      colon: a forgotten cause of refractory diarrhea.

PMID- 21170831
TI  - Use of endocytoscopy in the diagnosis of a rare, depressed-type ileal adenoma.

PMID- 21170832
TI  - Adenovirus-related gastric lesion in a patient with a bone marrow transplant.

PMID- 21170833
TI  - Verruciform xanthoma of the esophagus: an uncommon entity in an unusual site.

PMID- 21170834
TI  - Endoscopic ultrasound (EUS)-guided transluminal endoscopic removal of gallstones.

PMID- 21170835
TI  - Endoscopic hemostasis with hemoclips for active gastric variceal bleeding.

PMID- 21170836
TI  - Endoscopic treatment of acute ascending cholangitis in a patient with Roux-en-Y
      limb obstruction after a Whipple operation.

PMID- 21170837
TI  - The wing stent facilitates repeat bile duct cannulation for multiple stent
      insertion.

PMID- 21170838
TI  - Tracheoesophageal fistula following implantation of a biodegradable stent for a
      refractory benign esophageal stricture.

PMID- 21170839
TI  - Massive hemobilia from a ruptured hepatic artery aneurysm detected by endoscopic
      ultrasound (EUS) and successfully treated.

PMID- 21170840
TI  - Duodenal obstruction following papillary stenosis: a rare complication after
      endoscopic sphincterotomy.

PMID- 21170841
TI  - Pneumatosis coli as a rare complication of bowel preparation.

PMID- 21170842
TI  - Hybrid laparoscopic colectomy with transluminal colonoscopic specimen extraction-
      a step toward natural orifice surgery.

PMID- 21170843
TI  - Fibrin glue as a protective biomembrane for a duodenal ulcer vessel.

PMID- 21170844
TI  - A fulminant course of Cronkhite-Canada syndrome.

PMID- 21170845
TI  - Rectal perforation from cholesterol embolization syndrome.

PMID- 21170846
TI  - [Effect of compression stockings on physical endurance during a submaximal
      treadmill test].

PMID- 21170847
TI  - Kidney removal: the past, presence, and perspectives: a historical review.
AB  - More than 140 years have passed since the first documented planned nephrectomy.
      Throughout all these years, people gained significant knowledge on the renal
      functions and diseases, and what is more, the surgical workshop underwent
      considerable improvement. Initially, the kidney removal operations were performed
      due to ureterovaginal fistulas and renal lithiasis. Later, they were executed
      mainly in patients with renal tumors, whereas today, the number of these
      surgeries tend to decrease to the benefit of nephron sparing procedures. Current
      nephrectomies are more and more often performed in case of organ donation, what
      will probably remain the most significant indication for the kidney removal in
      close future. While the first surgeries were executed with classical surgical
      methods, nowadays, after years of studies concerning nephron sparing and
      minimally invasive operations, we can see surgeries carried out through natural
      body orifices with robotic assistance. In relation to simple surgical operation
      based on ligation of 3 tubular anatomic structures, we can perceive the true
      scope of the progress that occurred in surgery. The aim of this article is to
      present the evolution of indications and operating techniques utilized to remove
      the kidney in chronological aspect.

PMID- 21170848
TI  - Tuberous sclerosis complex.

PMID- 21170849
TI  - Gas in the renal area: emphysematous pyelonephritis.

PMID- 21170850
TI  - Evaluation of the learning curve for percutaneous nephrolithotomy.
AB  - PURPOSE: To determine the number of percutaneous nephrolithotomy (PCNL)
      operations which are required to achieve competence or excellence. MATERIALS AND
      METHODS: One hundred and five consecutive PCNL operations performed by a fellow
      in endourology, with no previous experience in performing solo PCNL, were
      studied. Operation duration, stone extraction percent, stone-free rate, number of
      access, tubeless cases, and complications were studied in sequential groups of 15
      patients as the surgeon gained experience. RESULTS: Operation duration decreased
      from the mean of 95.4 minutes in the first to 15th patients to 78.3 minutes in
      the 31st to 45th patients, and then remained unchanged. Minor complications were
      only observed in the first to 45th patients. Stone extraction percent increased
      from the mean of 88.3% in the first to 15th patients to 99.3% in 91st to 105th
      patients. Percentage of patients with no residual fragments decreased from 53% in
      the first to 15th patients to 6.7% in the 91st to 105th patients. No
      statistically significant differences were observed in estimated blood loss or
      transfusion rate between sequential groups of subjects. CONCLUSION: An
      improvement in operation duration was observed, and absence of complications was
      achieved after 45 cases. The improvement in stone clearance was observed up to
      the last subjects. Competence and excellence were achieved after 45 and 105
      operations, respectively.

PMID- 21170851
TI  - Antiurolithiatic activity of Pinus eldarica medw: fruits aqueous extract in rats.
AB  - PURPOSE: To evaluate the antiurolithiatic activity of Pinus eldarica fruit on
      induced calcium oxalate nephrolithiasis in rats. MATERIALS AND METHODS: Calcium
      oxalate nephrolithiasis in rats was induced by administering ethylene glycol 1%
      for 30 days via drinking water. The prophylactic and therapeutic groups received
      P. eldarica fruit extract (500 and 1000 mg/kg/day) as well for 30 days and from
      the 14th day through the end of the experiment, respectively. The following
      variables were assessed; urine volume, urinary calcium excretion, and
      crystalluria. Finally, rats' kidneys were histopathologically examined. RESULTS:
      The aqueous extract prophylactic treatment (500 mg/kg/day) increased urinary
      calcium excretion. Qualitative analysis of crystalluria and histopathologic
      examination showed that the administered dose of extract prevented stone
      formation in the kidneys significantly. The prophylactic treatment did not
      increase urine volume in comparison with ethylene glycol. Stone formation did not
      decrease in the treatment group. CONCLUSION: This study indicates that P.
      eldarica fruit extract prevents calcium oxalate deposition, without producing
      diuresis.

PMID- 21170852
TI  - Intracorporeal tapering of the ureter for distal ureteral stricture before
      laparoscopic ureteral reimplantation.
AB  - PURPOSE: To present our experience of laparoscopic ureteral reimplantation using
      intracorporeal ureteral tapering for management of distal ureteral stricture.
      MATERIALS AND METHODS: Between April 2005 and October 2008, six patients,
      including 3 children and 3 adults, underwent laparoscopic modified Lich-Gregoir
      type extravesical ureteral reimplantation for distal ureteral stricture.
      Significant dilatations of proximal segment in these patients were repaired with
      intracorporeal ureteral tapering. Stricture etiologies were congenital
      ureterovesical megaureter and iatrogenic gynecologic injury in 4 and 2 patients,
      respectively. RESULTS: Mean age of the patients was 29.3 years (range, 2 to 62
      years). Mean operation time and hospital stay was 185 minutes (range, 150 to 240
      minutes) and 4 days (range, 2 to 6 days), respectively. No significant
      complications were noted intra-operatively. Surgical procedure was performed in
      all the subjects laparoscopically and no conversion to open surgery happened.
      Postoperatively, 2 patients were complicated with febrile urinary tract infection
      that were managed medically. No urinary leakage occurred in early postoperative
      period. All the patients had patent ureterovesical junction anastomosis in follow
      up imaging and recurrence of obstruction was noted in no cases. Two patients
      (33.3%) developed grade II vesicoureteral reflux. CONCLUSION: Laparoscopic
      ureteral reimplantation with intracorporeal tapering of distal segment may be
      performed safely in management of patients with distal ureteral stricture and
      severe dilatation of proximal segment.

PMID- 21170853
TI  - Radical prostatectomy practice in England.
AB  - PURPOSE: As there is paucity of data on radical prostatectomy (RP) as a primary
      treatment for patients with localized prostate cancer, we analyzed the trends in
      the RP practice in England. MATERIALS AND METHODS: This study was carried out on
      14 300 patients who underwent RP for carcinoma of the prostate. Database was
      prepared from hospital episode statistics of the Department of Health in England.
      National trends in RP practice were summarized as well as volume outcome
      analysis. RESULTS: Annual number of RPs exponentially increased from 972 (1998 to
      1999) to 3092 (2004 to 2005). Laparoscopic RPs increased from 2 to 257 over the
      study period. Median waiting duration increased by more than 10 days (13 days).
      Significant decrease in median length of hospital stay from 8 (range, 7 to 10)
      days to 6 (range, 5 to 8) days was observed (P < .001). More than 90% mortality
      was seen in patients of >= 60 years of age. Significant inverse correlation was
      found between the hospital volume (Odds Ratio: 0.40) and in-hospital mortality
      rate following RP. High volume surgeons (>= 16) and high volume hospitals (>= 26)
      had significantly lower mortality (Odds Ratio: 0.32) and shorter in-hospital stay
      in comparison to low volume surgeons and hospitals. CONCLUSION: There is an
      exponential increase in the number of RPs with an increasing trend towards
      laparoscopic RP in England. This study showed a significant inverse correlation
      between provider volume (hospital and surgeon) and outcome (in-hospital mortality
      and hospital stay) for RP in England; thus, supporting the recommendations for
      centralization of care for complex radical procedures, including RP.

PMID- 21170854
TI  - Improvement of urodynamic indices by single dose oral tadalafil in men with supra
      sacral spinal cord injury.
AB  - PURPOSE: To investigate the changes in urodynamic indices following a single dose
      of oral tadalafil in patients with supra sacral spinal cord injury (SCI).
      MATERIALS AND METHODS: Urodynamic study was accomplished on 20 patients with
      supra sacral SCI before and one hour after administration of 20 mg oral tadalafil
      as a single dose. Changes in the bladder capacity and compliance, maximum voiding
      detrusor pressure, and maximum detrusor filling pressure before and after
      tadalafil administration were recorded. RESULTS: Following administration of 20
      mg oral tadalafil, there was a significant increase in the bladder compliance
      (from 12.7 to 18.5 mL/cmH2O, P < .001), bladder capacity (from 169.8 to 198.5 mL,
      P < .001), maximum voiding detrusor pressure (from 64.8 to 48.6 cmH2O, P < .001),
      and maximum detrusor filling pressure (from 24.3 to 14.0 cmH2O, P < .001).
      CONCLUSION: Single dose of oral tadalafil has significant positive effects on
      urodynamic indices in patients with supra sacral SCI.

PMID- 21170855
TI  - Tunica vaginalis flap as a second layer for tubularized incised plate
      urethroplasty.
AB  - PURPOSE: To investigate the success rate of Snodgrass method in combination with
      tunica vaginalis flap as the second layer for hypospadias repair. MATERIALS AND
      METHODS: In a prospective study, 33 patients with penile hypospadias who were
      treated using a Tubularized Incised Plate Urethroplasty (Snodgrass method) and
      vascularized tunica vaginalis flap as a second layer, were evaluated. Wound
      infections, meatal stenosis, and urethrocutaneous fistula were considered as
      treatment complications. Success rates of surgery were recorded. Failure was
      defined as need for re-operation. RESULTS: The mean age of the patients was 9.93
      +/- 4.4 years (range, 1.5 to 18 years). The mean follow-up was 8.79 +/- 5.43
      months (range, 6 months to 5 years). Four patients were lost to follow-up and
      excluded from the study. The location of hypospadias was distal penile in 17
      patients (59%) and midpenile in 12 (41%). Of studied patients, 3, 2, and, 1
      developed fistula, wound infection, and meatal stenosis, respectively. Two
      subjects with meatal stenosis and one with wound infection were managed
      conservatively. CONCLUSION: Snodgrass technique in combination with tunica
      vaginalis flap as a second layer is a reasonable procedure for hypospadias repair
      because of good cosmetic appearance and acceptable complication rates. Currently,
      fistula formation remains the most common complication of this technique, which
      often needs surgical repair.

PMID- 21170856
TI  - Dorsal versus ventral anterior urethral spatulation in posterior urethroplasty.
AB  - PURPOSE: To compare dorsal versus ventral anterior urethral spatulation in
      posterior urethroplasty. MATERIALS AND METHODS: In a retrospective study, we
      evaluated the records of 320 posterior urethroplasties which have been done in
      our center over a 7-year period from January 2000 to December 2006. The results
      of dorsal and ventral anterior urethral spatulations were compared. RESULTS: The
      studied subjects consisted of 264 men and 54 prepubescent boys (<= 15 years) with
      the mean age of 23 years (range, 5 to 84 years). The mean follow-up was 52 months
      (range, 27 to 107 months). Six o'clock (group A) and 12 o'clock (group B)
      anterior urethral spatulations were performed in 101 (32%) and 219 (68%) of the
      patients, respectively. The success rates were 96% and 87.6% in groups A and B,
      respectively (P = .025). There were no urethro-rectal fistula and perineal wound
      infection during the follow-up period. CONCLUSION: Our data suggest that the
      dorsal anterior urethral spatulation in urethroplasty is more efficient than
      ventral anterior urethral spatulation in terms of treatment success outcome.

PMID- 21170857
TI  - Open prostatectomy versus transurethral resection of the prostate, where are we
      standing in the new era? A randomized controlled trial.
AB  - PURPOSE: To compare peri-operative and short-term complications of open
      transvesical prostatectomy (OP) as well as its functional outcomes with
      transurethral resection of the prostate (TURP) in management of benign prostatic
      hyperplasia with prostates sized 30 to 70 g. MATERIALS AND METHODS: Hundred
      patients who were candidate for the prostate surgery with prostates between 30 to
      70 g randomly underwent OP or TURP. Secondary endpoints included international
      prostate symptom score, residual urine volume, surgical complications, and
      patients' quality of life. Patients were followed up for 6 to 12 months after the
      operation. RESULTS: Fifty-one and 49 patients underwent OP and TURP,
      respectively. Median (interquartile range) of peak flow rate improvement was 11.1
      (7.6 to 14.2) and 8.0 (2.2 to 12.6) in OP and TURP groups, respectively (P =
      .02). International prostate symptom score improvement did not reveal
      statistically significant difference between treatment groups. Re-operation due
      to residual prostate lobe, urethral stricture, and urinary retention was
      performed in 8 patients in TURP group versus no patient in OP group (P = .006).
      Dysuria was more frequent in patients that underwent TURP (P < .001).
      Hospitalization duration was slightly longer in patients that underwent OP (P =
      .04). Patients' quality of life was better in the OP group (P = .04). CONCLUSION:
      Open transvesical prostatectomy is an acceptable operation for the prostates
      sized 30 to 70 g. Higher peak flow rate improvement, better quality of life, less
      frequent dysuria, less need to re-operation, and its ease of learning make open
      prostatectomy a suitable option to be discussed in patients parallel to TURP.

PMID- 21170858
TI  - Endoscopic treatment of a primary prostatic hydatid cyst: a mini-invasive
      therapeutic approach.

PMID- 21170859
TI  - A complication after percutaneous nephrolithotomy.

PMID- 21170860
TI  - Percutaneous drainage for treatment of prostate abscess.

PMID- 21170861
TI  - Malignant sertoli cell tumor of the testis with a large retroperitoneal mass in
      an elderly man.

PMID- 21170862
TI  - Disfiguring abdominal mass due to a huge extraordinary calyceal diverticulum.

PMID- 21170863
TI  - Intestinal metaplasia of the renal pelvis.

PMID- 21170865
TI  - Renal pathophysiology: is it still necessary?

PMID- 21170866
TI  - Clinical hypokalemia and hyperkalemia at the bedside.
AB  - Hypokalemia and hyperkalemia are commonly encountered in clinical practice, but
      the pathophysiology of these common disorders is often not fully appreciated.
      This article reviews the mechanisms of potassium dysregulation and presents a
      framework for the diagnosis and treatment of these common electrolyte disorders.

PMID- 21170867
TI  - Hypertension and renal calcium transport.
AB  - Calcium homeostasis is altered in hypertensive patients. Indeed several
      investigators have reported that sodium-sensitive hypertension is associated with
      hypercalciuria. On the other hand, an independent clinical association exists
      between the occurrence of urolithiasis and hypertension, but the molecular
      mechanism(s) involved in stone formation by high blood pressure have not been so
      far clarified. To understand this association, it is obvious that we should
      analyze the effect of hypertension on the transport proteins involved in the
      renal calcium handling. In the kidney, the tubular reabsorption of calcium may
      proceed through transcellular and paracellular routes. At variance with the
      proximal tubule, along the distal segment, calcium transport is entirely sodium
      independent and occurs via the transcellular pathway. In particular,
      transcellular calcium reabsorption proceeds through a well-controlled sequence of
      events consisting of luminal calcium entry via the epithelial calcium channel
      (TRPV5), cytosolic diffusion of calcium bound to calbindin-D28K, and basolateral
      extrusion of calcium through the Na/Ca exchanger (NCX1) and plasma membrane Ca
      ATPase (PMCA). It is highly likely that these proteins may be altered in
      hypertensive disease thus justifying and explaining the reported hypercalciuria.
      Experiments in hypertensive strains of animals exhibiting hypercalciuria may help
      to solve this puzzle.

PMID- 21170868
TI  - Pendrin and sodium channels: relevance to hypertension.
AB  - Renal intercalated cells mediate the secretion or the absorption of OH-/H+
      equivalents and Cl- in the distal convoluted tubule (DCT), the connecting tubule
      (CNT) and the cortical collecting duct (CCD). In so doing, they regulate acid
      base balance, vascular volume and blood pressure. In type B and non-A, non-B
      intercalated cells, Cl- absorption and HCO3- secretion are accomplished through
      the apical Na+-independent Cl-/HCO3- exchanger, pendrin. With increased
      circulating aldosterone or angiotensin II, pendrin abundance and function are up
      regulated. In the absence of pendrin (Slc26a4 (-/-) or pendrin null mice),
      aldosterone- and angiotensin II-stimulated Cl- absorption are reduced, which
      attenuates the blood pressure response to these hormones. Pendrin also modulates
      aldosterone-induced changes in ENaC abundance and function through a kidney
      specific mechanism that does not involve changes in the concentration of a
      circulating hormone. Instead, pendrin changes ENaC abundance and function, at
      least in part, by altering luminal HCO3-. Thus, aldosterone and angiotensin II
      modulate the renal regulation of blood pressure, in part, by regulating pendrin
      mediated Cl- absorption and ENaC-mediated Na+ absorption. This review summarizes
      the contribution of the Cl-/HCO3- exchanger, pendrin, in the renal regulation of
      blood pressure.

PMID- 21170870
TI  - The calcium-sensing receptor.
AB  - To maintain divalent ion concentration within the body, a complex sensor has
      evolved to identify the changes in the extracellular environment and cause the
      surrounding cells to either secrete or absorb in response to change. An important
      member of these "sensors" is the calcium-sensing receptor (CaSR), which is
      constantly monitoring the extracellular environment for changes in salinity, pH,
      calcium, amino acids and polyamines. The kidney plays a very important role in
      monitoring both salinity and also water concentration of the presented filtered
      load. Recent studies have shown that the CaSR is expressed along the nephron and
      can play an important role in both calcium and salt absorption, and also in the
      handling of water in the thick ascending limb. This review will outline the basic
      physiology of the receptor and will then go on to discuss some of the roles that
      the receptor plays in the various nephron segments. It will conclude with a brief
      section on future directions and how specific renal receptor-targeted drugs may
      provide an effective means to regulate both ionic absorption and water balance.

PMID- 21170869
TI  - SGK, renal function and hypertension.
AB  - Serum- and glucocorticoid-inducible kinase 1 (SGK1) is expressed following cell
      stress and exposure to a variety of hormones including glucocorticoids and
      mineralocorticoids. It is activated by insulin and growth factors via
      phosphatidylinositol-3-kinase and the 3-phosphoinositide-dependent kinase PDK1.
      SGK1 enhances the activity of a variety of ion channels such as ENaC, TRPV5,
      ROMK, KCNE1/KCNQ1 and ClCKb; carriers such as NHE3, NKCC2, NCC and SGLT1; as well
      as the Na+/K+-ATPase. SGK1 contributes to Na+ retention and K+ elimination of the
      kidney as well as mineralocorticoid stimulation of salt appetite. A certain SGK1
      gene variant (combined polymorphisms in intron 6 [I6CC] and in exon 8 [E8CC/CT])
      is associated with moderately enhanced blood pressure. The SGK1 gene variant has
      been shown to affect 3%-5% of whites and some 10% of Africans. The gene variant
      sensitizes the carriers to the hypertensive effects of hyperinsulinemia.
      Moreover, the SGK1 gene variant is associated with increased body mass index,
      presumably a result of enhanced SGLT1 activity with accelerated intestinal
      glucose absorption. Obesity predisposes the carriers of the gene variant to
      development of type 2 diabetes. Moreover, SGK1 stimulates coagulation. Thus, SGK1
      may participate in the pathogenesis of metabolic syndrome or syndrome X, a
      condition characterized by the coincidence of essential hypertension,
      procoagulant state, obesity, insulin resistance and hyperinsulinemia.

PMID- 21170872
TI  - Phosphate transport in the kidney.
AB  - In kidneys of mammals, filtered phosphate ions (Pi) are reabsorbed along the
      proximal tubules. Transcellular transport of phosphate is initiated by several
      apically localized sodium-dependent Pi cotransporters (Na/Pi-cotransporters) that
      belong to the SLC 20 (SLC20A2) and 34 (SLC34A1, SLC34A3) families. Apical
      abundance of these Na/Pi-cotransporters is adjusted by numerous
      hormones/phosphatonins and metabolic factors in order to adjust the extent of
      renal Pi reabsorption according to body needs. Acute hormonal regulation of Pi
      reabsorption occurs mainly by a change of the abundance of SLC34A1 (NaPi-IIa) via
      modulation of the interaction of NaPi-IIa with the PDZ-protein NHERF1.

PMID- 21170873
TI  - Ageing and changes in phosphate transport: clinical implications.
AB  - Hyperphosphatemia is pivotal in some complications secondary to kidney
      dysfunction. Current guidelines suggest that hyperphosphatemia secondary to
      kidney dysfunction develops only when glomerular filtration rate is reduced well
      below the threshold of 60 ml/min. This paper deals with the relationship of age
      with serum phosphorus and with the possible influences of this relationship on
      hyperphosphatemia secondary to kidney dysfunction. A recent epidemiologic study
      shows that serum phosphorus decreases over time not only in pediatric age but
      also during adulthood. This decrease differs between men and women: continuous in
      men, but not in women, because of a transitory serum phosphorus increase during
      climacterics. Data show also that age-associated differences in serum phosphorus
      among adults are explained by differences in the maximal phosphorus reabsorption
      in the renal proximal tubule (TmP/GFR). Other studies suggest that the opposite
      influences on TmP/GFR of growth hormone (stimulation) and estrogen (inhibition)
      are the determinants of the age-associated changes in TmP/GFR and serum
      phosphorus. The decline of serum phosphorus with age leads to the hypothesis
      that, in the presence of a disorder inducing phosphorus retention, the prevalence
      of hyperphosphatemia should be higher in young adults than in the elderly because
      the healthy elderly have lower serum phosphorus. A large clinical study supports
      this hypothesis showing that hyperphosphatemia secondary to kidney dysfunction is
      approximately 4 times higher at age <65 that at age >65. Data suggest that the
      relation between kidney function and serum phosphorus should be reevaluated
      considering the possible confounding effect of age.

PMID- 21170871
TI  - Klotho and kidney disease.
AB  - Klotho is a single-pass transmembrane protein that exerts its biological
      functions through multiple modes. Membrane-bound Klotho acts as coreceptor for
      the major phosphatonin fibroblast growth factor-23 (FGF23), while soluble Klotho
      functions as an endocrine substance. In addition to in the distal nephron where
      it is abundantly expressed, Klotho is present in the proximal tubule lumen where
      it inhibits renal Pi excretion by modulating Na-coupled Pi transporters via
      enzymatic glycan modification of the transporter proteins - an effect completely
      independent of its role as the FGF23 coreceptor. Acute kidney injury (AKI) and
      chronic kidney disease (CKD) are states of systemic Klotho deficiency, making
      Klotho a very sensitive biomarker of impaired renal function. In addition to its
      role as a marker, Klotho also plays pathogenic roles in renal disease. Klotho
      deficiency exacerbates decreases in, while Klotho repletion or excess preserves,
      glomerular filtration rate in both AKI and CKD. Soft tissue calcification, and
      especially vascular calcification, is a dire complication in CKD, associated with
      high mortality. Klotho protects against soft tissue calcification via at least 3
      mechanisms: phosphaturia, preservation of renal function and a direct effect on
      vascular smooth muscle cells by inhibiting phosphate uptake and
      dedifferentiation. In summary, Klotho is a critical molecule in a wide variety of
      renal diseases and bears great potential as a diagnostic and prognostic biomarker
      as well as for therapeutic replacement therapy.

PMID- 21170874
TI  - Role of SLC26A6-mediated Cl--oxalate exchange in renal physiology and
      pathophysiology.
AB  - Although a major fraction of Cl- reabsorption in the proximal tubule is passive
      and paracellular, there is an additional component of Cl- transport that is
      transcellular. A search for possible mechanisms that might mediate Cl- uptake
      into proximal tubule cells led to the identification of an apical membrane Cl-
      oxalate exchange activity. Subsequent studies identified anion transporter
      SLC26A6 as responsible for proximal tubule Cl--oxalate exchange activity. The
      most striking phenotype in Slc26a6 null mice was calcium oxalate urolithiasis due
      to hyperoxaluria. Hyperoxalemia and hyperoxaluria in Slc26a6 null mice were found
      to be caused by defective intestinal back-secretion of ingested oxalate. These
      findings suggested that inherited or acquired defects in SLC26A6 might lead to
      hyperoxaluria and increased stone risk, and have motivated studies to
      characterize the role of SLC26A6 in oxalate homeostasis in patients and in animal
      models.

PMID- 21170875
TI  - Urinary pH and stone formation.
AB  - The formation of various types of kidney stones is strongly influenced by urinary
      pH. An alkaline pH favors the crystallization of calcium- and phosphate
      containing stones, whereas and acidic urine pH promotes uric acid or cystine
      stones. The activity of many transport processes involved in calcium, citrate and
      phosphate handling are sensitive to changes in systemic or local pH as shown for
      several phosphate transporters, the citrate transporter NaDC1 and the TRPV5
      calcium channel. Defects in urinary acidification (excretion of inappropriately
      alkaline or acidic urines, respectively) contribute to kidney stone disease. The
      low excretion of ammonium in patients with metabolic syndrome has been linked to
      more acidic urine and a higher incidence of uric acid stones. In this state,
      insulin resistance may reduce ammonium excretion by the proximal tubule. On the
      other hand, defensive mechanisms may protect from kidney stone formation in
      conditions such as hypercalciuria where high luminal calcium concentrations
      stimulate urinary acidification and reduce urinary concentration via a calcium
      sensing receptor, resulting in the excretion of acidic and diluted urine. This
      review will discuss a few aspects that relate to the capacity of the kidney to
      regulate pH and its impact on the excretion of solutes that participate in the
      formation or prevention of stones.

PMID- 21170876
TI  - Water channels in peritoneal dialysis.
AB  - Peritoneal dialysis involves diffusive and convective transports and osmosis
      through the highly vascularized peritoneal membrane. Several lines of evidence
      have demonstrated that the water channel aquaporin-1 (AQP1) corresponds to the
      ultrasmall pore predicted by the modelization of peritoneal transport. Proof-of
      principle studies have shown that up-regulation of the expression of AQP1 in
      peritoneal capillaries is reflected by increased water permeability and
      ultrafiltration, without affecting the osmotic gradient and the permeability for
      small solutes. Inversely, studies in Aqp1 mice have shown that haploinsufficiency
      in AQP1 is reflected by significant attenuation of water transport. Recent
      studies have identified lead compounds that could act as agonists of aquaporins,
      as well as putative binding sites and potential mechanisms of gating the water
      channel. By modulating water transport, these pharmacological agents could have
      clinically relevant effects in targeting specific tissues or disease states.
      These studies on the peritoneal membrane also provide an experimental framework
      to investigate the role of water channels in the endothelium and various cell
      types.

PMID- 21170877
TI  - Calcium and phosphate changes after renal transplantation.
AB  - Hypercalcemia and hypophosphatemia are frequently observed in recipients of a
      kidney transplant (KTx). Hypercalcemia has been reported in up to 66% of KTx
      patients. Many factors have been suggested as the putative causal factors;
      however, the persistence of moderate-severe secondary hyperparathyroidism,
      associated with a change in the set-point of the Ca-controlled parathyroid
      hormone (PTH) secretion, is considered to play a prominent role. Hypercalcemia
      can negatively impact on both the graft and patient outcome, increasing the
      incidence of nephrocalcinosis, which can induce a worse graft outcome, inducing
      vascular calcifications, and increasing the incidence of pancreatitis. In
      addition, severe hypercalcemia after KTx often requires parathyroidectomy, which
      is not universally considered a safe medical solution in this clinical setting.
      After KTx, phosphate levels often fall below the normal range, with
      hypophosphatemia being observed in up to 40% of patients. The putative causal
      factors for this metabolic alteration are persistent hyperparathyroidism,
      increased levels of FGF-23, tubular damage secondary to the immunological
      effects, and toxic and vascular effectors. Hypophosphatemia can negatively impact
      on either skeletal or muscular systems, contributing to the increased incidence
      of bone fractures in KTx patients. The current therapeutic options should take
      into account an accurate pretransplant treatment and screening of the waiting
      list patient and should also evaluate the efficacy and safety profile of the new
      pharmacological tools (calcimimetics) in comparison with the classical surgical
      approach (parathyroidectomy).

PMID- 21170878
TI  - Dyselectrolytemias and arrhythmias.
AB  - Critical care patients are submitted to multiple derangements of vital
      parameters. Even in patients with a normally performing heart, its electrical
      activity can be strongly influenced by dyselectrolytemias, acid-base imbalance
      and aggressive drug therapy. In this paper, the basic principles of the
      electrophysiologic properties of the heart are reviewed, and the impact of
      dyselectrolytemias on heart excitability are underlined. Some clinically relevant
      aspects are described in greater depth, with respect to life-threatening
      arrhythmias.

PMID- 21170879
TI  - Acid-base transport by the renal distal nephron.
AB  - The functional versatility of the distal nephron is mainly due to the large
      cytological heterogeneity of the segment. Part of Na+ uptake by distal tubules is
      dependent on Na+/H+ exchanger 2 (NHE2), implicating a role of distal convoluted
      cells also in acid-base homeostasis. In addition, intercalated (IC) cells
      expressed in distal convoluted tubules, connecting tubules and collecting ducts
      are involved in the final regulation of acid-base excretion. IC cells regulate
      acid-base handling by 2 main transport proteins, a V-type H+-ATPase and a Cl/HCO3
      exchanger, localized at different membrane domains. Type A IC cells are
      characterized by a luminal H+-ATPase in series with a basolateral Cl/HCO3-
      exchanger, the anion exchanger AE1. Type B IC cells mediate HCO3- secretion
      through the apical Cl-/HCO3- exchanger pendrin in series with a H+-ATPase at the
      basolateral membrane. Alternatively, H+/K+-ATPases have also been found in
      several distal tubule cells, particularly in type A and B IC cells. All of these
      mechanisms are finely regulated, and mutations of 1 or more proteins ultimately
      lead to expressive disorders of acid-base balance.

PMID- 21170880
TI  - Regulation of sodium transporters in the kidney during cyclosporine treatment.
AB  - Cyclosporine (CsA) is among the most widely used immunosuppressants for
      preventing graft rejection and autoimmune diseases. However, its clinical use is
      hampered by its significant nephrotoxicity and effects as a cause of
      hypertension. The proximal tubular Na+-H+ exchanger (NHE3) is responsible for
      transcellular reabsorption of 30%-60% of the sodium filtered by the glomerulus.
      CsA induces a reduction of absolute sodium reabsorption, and this effect is, most
      probably, correlated with the decrease of NHE3 activity. In Henle's loop, in
      physiological conditions, the Na+-K+-2Cl- cotransporter (NKCC2) reabsorbs
      approximately 20% of the filtered Na+ and Cl-. CsA increases the NKCC2 activity
      in cultured bovine renal NBL-1 cells. In the collecting duct, CsA may cause
      hypertension by stimulating the epithelial Na+ channel (ENaC) through a pathway
      associated with inhibition of ABCA1 and consequent elevation of cholesterol in
      the cells. It is still unclear whether CsA regulates the Na+-Cl- cotransporter in
      the distal tubule and ENaC in the collecting duct. Aside from this, there is
      evidence suggesting the possible involvement of free radicals during the
      development of CsA-induced hypertension. The hypertensive effect is, most
      probably, correlated with higher levels of superoxide (O2-) that decreases
      glomerular filtration rate and may affect fluid reabsorption along the nephron.

PMID- 21170881
TI  - Fabry disease: perspectives of urinary proteomics.
AB  - Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations
      in the gene encoding the lysosomal enzyme a-galactosidase A (a-GalA). The
      resulting deficiency in a-GalA activity leads to intra-lysosomal accumulation of
      neutral glycosphingolipids, mainly globotriaosylceramide (Gb3), in various organ
      systems. As a consequence, a multisystem disorder develops, culminating in
      strokes and progressive renal and cardiac dysfunction. Enzyme replacement therapy
      (ERT) offers a specific treatment for patients affected by FD, though monitoring
      treatment is hampered by a lack of surrogate markers of response. Furthermore,
      even if signs and symptoms of the disease become manifest in childhood, its
      diagnosis is often delayed. Biomarkers that predict disease progression and
      respond relatively quickly to effective therapy may be useful to follow
      individual patients or groups of patients. Here we report the use of 2 different
      mass spectrometry-based proteomic techniques to identify disease-associated
      compositional changes that can be used as early biomarkers of the pathology, as
      well as for monitoring the effectiveness of ERT. To this purpose, we compared the
      renal Fabry urinary proteome with normal (control) urine using, respectively, 2
      dimensional gel electrophoresis and label-free quantification. Our preliminary
      results show that the urinary protein pattern of affected patients can be easily
      distinguished from that of healthy subjects both qualitatively and
      quantitatively, thus encouraging further studies in the search for FD-specific
      biomarkers using this proteomic approach.

PMID- 21170883
TI  - Perspectives of 1H-NMR-based urinary metabonomics in Fabry disease.
AB  - High resolution proton magnetic resonance spectroscopy (1H-NMR) of body fluids
      coupled with multivariate data analysis has led to a new science known as
      metabonomics. Metabonomics is a powerful tool for investigating any disturbance
      in the normal homeostasis of biochemical processes. In particular, urine
      metabonomics provides information on the metabolite phenotype of the human being
      and is therefore appropriate to study the status of the global system. Here we
      applied 1H-NMR-based urinary metabonomics in a perspective study of the inherited
      lysosomal storage disorder known as Fabry disease, starting from the metabolite
      profiling of urine samples of male and female naive Fabry subjects. Here we show
      that the 2 groups of patients can be fairly clearly separated into 2 classes due
      to statistically significant differences in the urinary level of some
      metabolites. This preliminary study shows that metabonomics can potentially be
      used for characterizing the biochemical mechanisms underlying the disease and,
      hopefully, for early diagnosis of Fabry disease.

PMID- 21170884
TI  - Proteomics and tubulopathies.
AB  - In the last thirty decade, with the emergence of new trends in molecular biology
      and advances in high-throughput technologies, much progress has been made in
      basic renal physiology. Molecular genetics has allowed the identification and
      elucidation of the structure, function and effects of the mutations of several of
      the main transporters and ion channels involved in renal disorders. Some renal
      stone disorders, such as cystinuria and Dent's disease, have been found to be due
      to mutations in genes SLC3A1 (type I) (See the section "Molecular biology and
      genotype-phenotype correlation in tubular dysfunction") and SLC7A9 (type II and
      type III), (See the section "Molecular biology and genotype-phenotype correlation
      in tubular dysfunction") and in CLC5, respectively. Liddle syndrome, a rare cause
      of hypertension, is now known to be caused by a mutation in tubular transport,
      due to a mutation in the SCNN1B gene, encoding for a Na+ channel protein (ENaC).
      Nevertheless, numerous issues remain unsettled and warrant additional research.
      These important advances and discoveries are not without limitations and
      challenges as changes in individual gene expression do not always translate into
      changes in its protein or protein modification. This raises proteomics as the
      most logical next step in our understanding of biological processes, as proteins
      from these deregulated genes are the functional agents in the cells. Proteomics
      takes a global and comprehensive view of a system, involving in many cases some
      notion of high throughput; but in contrast to genomics, there is no single
      biochemical method that can be used for the analysis of all proteins. Genomics
      and proteomics can complement each other in clinical applications by balancing
      the strengths and weaknesses of each individual technology. Several proteomics
      approaches have been exploited to shed more light on the molecular
      pathophysiology of several hereditary tubular disorders, such as Fanconi and
      Gitelman syndromes, and have provided important insights into the defective
      molecular mechanisms underlying these tubulopathies. Here we summarize several of
      the most important discoveries arising from molecular genetic and proteomic
      studies on hereditary tubular dysfunctions and show how these results can
      complement each other to increase our comprehension of these disorders at the
      molecular level.

PMID- 21170885
TI  - Ammonium transport in the kidney.
AB  - Ammonium excretion into the urine is the main mechanism of renal acid excretion.
      Ammonium is produced by epithelial cells of the proximal tubule and then secreted
      into the luminal fluid. However, before its final excretion into urine, ammonium
      ion is reabsorbed by the thick ascending limb (TAL), and accumulated in the
      interstitium to build up a corticopapillary gradient of ammonium which is
      necessary for the final diffusion of the gas NH3 in parallel to active proton
      secretion. Recent evidence has been provided by the study of several mouse models
      of renal acidosis. Particularly, it has been shown that the Na+/H+ exchanger NHE4
      is a critical step of ammonium absorption by the TAL, and also that NH3 diffusion
      across the membrane of collecting duct cells requires the presence of the
      recently identified gas channel Rhcg. This review is an update on the different
      mechanisms of ammonium transport along the nephron, with a particular emphasis on
      these new molecules.

PMID- 21170886
TI  - Na+-coupled bicarbonate transporters in duodenum, collecting ducts and choroid
      plexus.
AB  - Epithelia cover the internal and external surfaces of the organism and form
      barriers between the various compartments. Some of these epithelia are
      specialized for effective transmembrane or even transepithelial movement of acid
      base equivalents. Certain epithelia with a high rate of HCO3- transport express a
      few potent Na+-coupled acid-base transporters to gain a net HCO3- movement across
      the epithelium. Examples of such epithelia are renal proximal tubules and
      pancreatic ducts. In contrast, multiple Na+-coupled HCO3- transporters are
      expressed in other HCO3- secreting epithelia, such as the duodenal mucosa or the
      choroid plexus, which maintain suitable intracellular pH despite a variable
      demand for secreting HCO3-. In the duodenum, the epithelial cells must secrete
      HCO3- for neutralization of the gastric acid, and at the same time prevent
      cellular acidification. During the neutralization, large quantities of CO2 are
      formed in the duodenal lumen, which enter the epithelial cells. This would tend
      to lower intracellular pH and require effective counteracting mechanisms to avoid
      cell death and to maintain HCO3- secretion. The choroid plexus secretes the
      cerebrospinal fluid (CSF) and controls the pH of the otherwise poorly buffered
      CSF. The pCO2 of CSF fluctuates with plasma pCO2, and the choroid plexus must
      regulate the HCO3- secretion to minimize the effects of these fluctuations on CSF
      pH. This is done while maintaining pH neutrality in the epithelial cells. Thus,
      the Na+-HCO3- cotransporters appear to be involved in HCO3- import in more
      epithelia, where Na+/H+ exchangers were until recently thought to be sufficient
      for maintaining intracellular pH.

PMID- 21170888
TI  - Lithium-induced nephrogenic diabetes insipidus: new clinical and experimental
      findings.
AB  - Lithium (Li+) salts are widely used to treat bipolar mood disorders. Recent
      trials suggest a potential efficacy also in the treatment of amyotrophic lateral
      sclerosis and Alzheimer's disease. Li+ is freely filtered by the glomerulus and
      mainly reabsorbed in the proximal convoluted tubule. Reabsorption in the distal
      nephron becomes significant under sodium-restricted conditions. Nevertheless, the
      distal nephron is greatly affected by Li+ even under normal sodium intake.
      Polyuria, renal tubular acidosis and finally chronic renal failure are the most
      frequent adverse effects. The occurrence of an overt nephrogenic diabetes
      insipidus (NDI) limits Li+ usage and imposes suspension. The molecular mechanisms
      of Li+-related urinary concentration defect involve a dysregulation of the
      aquaporin system in principal cells of the collecting duct. ENaC is crucial as
      the entry route for intracellular Li+ accumulation. The basolateral exit route is
      not clearly identified, but some evidence suggests Na+/H+ exchanger 1 (NHE1) as a
      potential candidate. Li+ promotes polyuria mainly counteracting the intracellular
      vasopressin signaling. An additional role of the inner medullary interstitial
      cells and PGE-2 pathway has to be considered. The GSK3beta cascade is also
      regulated by Li+. GSK3beta inhibition could lead not only to the polyuria, but
      also to the Li+-dependent proliferative effect on principal cells. Cellular
      reorganization of the collecting duct and microcysts are the main pathological
      findings during Li+ treatment. Their relationship with the urinary concentration
      defect and an eventual Li+-induced ciliopathy has to been investigated. Li+
      induced NDI has been a matter of investigation since the early 1970s. This
      manuscript reports the latest clinical and experimental findings in combination
      with the older fundamental results.

PMID- 21170889
TI  - Low urinary citrate: an overview.
AB  - Hypocitraturia is a known risk factor for kidney stone formation. By forming
      soluble complexes with calcium, citrate prevents crystal nucleation, aggregation
      and growth; therefore, the presence of citrate in the urine reduces the risk for
      calcium stone formation. Ingested citrate is rapidly metabolized, and plasma
      citrate levels vary little, so changes in filtered load do not significantly
      influence urinary citrate excretion. Changes in urinary citrate excretion are
      predominantly influenced by the rate of citrate absorption from the glomerular
      filtrate and metabolism by the proximal tubule cell. The former is mediated by
      the apical membrane cotransporter NaDC1, and the latter is mediated by both
      cytoplasmic and mitochondrial metabolism. Acid-base status is the most important
      physiological determinant of urinary citrate excretion, by modulating the
      activities of NaDC1 and cytoplasmic (ATP citrate lyase) and mitochondrial (m
      aconitase) enzymes involved in citrate metabolism. Following an acid load, both
      the transport and metabolic processes are up-regulated leading to hypocitraturia;
      in contrast, an alkaline load increases citrate excretion, by regulating only the
      mitochondrial metabolic process.

PMID- 21170890
TI  - Familial renal tubular acidosis.
AB  - The kidney maintains systemic acid-base homeostasis through proximal tubular
      reclamation of filtered bicarbonate, and excretion of the daily mineral acid load
      by collecting duct type A intercalated cells. Impairment of either process
      produces renal tubular acidosis (RTA). This article will provide an overview of
      familial forms of proximal and distal renal tubular acidosis (pRTA and dRTA).
      Recessive pRTA with ocular and central nervous system abnormalities is caused by
      loss-of-function mutations in basolateral membrane Na-HCO3- cotransporter NBCe1/
      SLC4A4. Recessive dRTA with deafness is caused by loss-of-function mutations in
      either of 2 subunits of the vacuolar H+-ATPase (V-ATPase) of intercalated cells;
      the B1 subunit of the V1 cytoplasmic ATPase complex, and the a4 subunit of the V0
      transmembrane pore complex. Dominant and recessive forms of dRTA are also caused
      by loss-of-function mutations in the basolateral membrane AE1 Cl-/HCO3- exchanger
      of the type A intercalated cell. The dominant AE1 dRTA mutations are accompanied
      by mild or asymptomatic erythroid changes, while the erythroid dyscrasias
      accompanying recessive AE1 dRTA mutations can be mild or severe. Recessive mixed
      proximal-distal RTA is caused by loss-of-function mutations of the cytoplasmic
      carbonic anhydrase II. Hyperkalemic RTA accompanied by hypertension
      (pseudohypoaldosteronism type 2 [PHA2]) is caused by dominant gain-of-function
      mutations in the kinases WNK1 and WNK4. Hyperkalemic RTA accompanied by volume
      depletion is caused by loss-of-function mutations in genes encoding the
      mineralocorticoid receptor or the epithelial Na+ channel (ENaC) subunits.
      Additional RTA genes identified in knockout mice may lead to identification of
      additional human RTA genes.

PMID- 21170887
TI  - Acid-base transport by the renal proximal tubule.
AB  - Each day, the kidneys filter 180 L of blood plasma, equating to some 4,300 mmol
      of the major blood buffer, bicarbonate (HCO3-). The glomerular filtrate enters
      the lumen of the proximal tubule (PT), and the majority of filtered HCO3- is
      reclaimed along the early (S1) and convoluted (S2) portions of the PT in a manner
      coupled to the secretion of H+ into the lumen. The PT also uses the secreted H+
      to titrate non-HCO3- buffers in the lumen, in the process creating "new HCO3-"
      for transport into the blood. Thus, the PT - along with more distal renal
      segments - is largely responsible for regulating plasma [HCO3-]. In this review
      we first focus on the milestone discoveries over the past 50+ years that define
      the mechanism and regulation of acid-base transport by the proximal tubule.
      Further on in the review, we will summarize research still in progress from our
      laboratory, work that addresses the problem of how the PT is able to finely adapt
      to acid-base disturbances by rapidly sensing changes in basolateral levels of
      HCO3- and CO2 (but not pH), and thereby to exert tight control over the acid-base
      composition of the blood plasma.

PMID- 21170891
TI  - Effects of acidogenic diet forms on musculoskeletal function.
AB  - Chronic metabolic acidosis exerts well-characterized consequences on
      musculoskeletal function, including physicochemical dissolution of bone with
      calcium loss from bone, cellular effects on osteoblasts and osteoclasts and
      disturbed bone matrix mineralization. These mechanisms are responsible for the
      acidotic bone phenotype with features of both osteoporosis and osteomalacia. In
      addition, loss of muscle mass, sarcopenia and negative nitrogen balance are
      consequences of metabolic acidosis. It is becoming increasingly clear that these
      effects also occur as a consequence of the diet-induced acid loads characteristic
      of modern diets. Interventional, short- and long-term studies suggest that the
      result of neutralizing the diet-induced acid loads is skeletal calcium retention,
      decreased bone resorption and increases in bone mineral density, suggesting that
      such an intervention may have an important potential to prevent osteoporosis.

PMID- 21170892
TI  - Renal acidification responses to respiratory acid-base disorders.
AB  - Respiratory acid-base disorders are those abnormalities in acid-base equilibrium
      that are expressed as primary changes in the arterial carbon dioxide tension
      (PaCO2). An increase in PaCO2 (hypercapnia) acidifies body fluids and initiates
      the acid-base disturbance known as respiratory acidosis. By contrast, a decrease
      in PaCO2 (hypocapnia) alkalinizes body fluids and initiates the acid-base
      disturbance known as respiratory alkalosis. The impact on systemic acidity of
      these primary changes in PaCO2 is ameliorated by secondary, directional changes
      in plasma [HCO3-] that occur in 2 stages. Acutely, hypercapnia or hypocapnia
      yields relatively small changes in plasma [HCO3-] that originate virtually
      exclusively from titration of the body's nonbicarbonate buffers. During sustained
      hypercapnia or hypocapnia, much larger changes in plasma [HCO3-] occur that
      reflect adjustments in renal acidification mechanisms. Consequently, the
      deviation of systemic acidity from normal is smaller in the chronic forms of
      these disorders. Here we provide an overview of the renal acidification responses
      to respiratory acid-base disorders. We also identify gaps in knowledge that
      require further research.

PMID- 21170893
TI  - The gasotransmitter hydrogen sulfide in hemodialysis patients.
AB  - Hydrogen sulfide, H2S, is the third endogenous gas with cardiovascular properties
      (the others are nitric oxide and carbon monoxide). In fact, among other important
      signaling functions, H2S plays a key role in regulating blood pressure.
      Cystathionine beta-synthase, cystathionine gamma-lyase (CSE) and 3
      mercaptopyruvate sulfurtransferase are the principal enzymes devoted to H2S
      formation. We have recently shown that H2S levels are decreased in patients on
      chronic hemodialysis through the transcriptional deregulation of the CSE gene,
      hinting at the possibility that a link exists between this finding and
      hypertension and the high cardiovascular mortality typical of these patients.

PMID- 21170894
TI  - Potassium transport--an update.
AB  - Potassium homeostasis depends on the coordinated interaction between tightly
      regulated potassium transfer in and out of the extracellular fluid compartment,
      and renal excretion or retention of potassium. Potassium transport along the
      nephron involves extensive proximal tubule reabsorption of potassium. Potassium
      is also reabsorbed along the thick ascending limb of Henle's loop. Regulated
      potassium secretion, or potassium reabsorption in exchange for hydrogen ions
      along the connecting tubule and collecting tubule, is responsible for potassium
      excretion. Renal potassium transport is modulated by potassium intake, several
      hormones, acid-base factors and distal nephron sodium delivery. WNK family
      kinases have also emerged as factors regulating sodium and potassium transport in
      the distal nephron.

PMID- 21170900
TI  - A gaussian model for substrates of entangled cross-linked poly(ethylene glycol)
      in biomedical applications.
AB  - Cells usually spread on a synthetic substrate through bonds between receptors and
      chemical groups on the substrate (ligands). Therefore, it is valuable to study
      the effects of the average number density of these chemical groups and the
      average distance between them to model and predict the cell behavior.
      Poly(ethylene glycol) [PEG] modified with peptide groups has been used widely in
      biomedical applications as a substrate material. In this study, a coarse-grained
      model is proposed for PEG to predict the average number density of ligands and
      the average distance between them. Molecular information such as initial
      molecular weight distribution, average molecular weight between cross-links, and
      average molecular weight between entanglements is used as input parameters. Based
      on simulation results, it is concluded that both entanglement and cross-link
      densities are required to create a network structure. The results suggest that an
      average initial molecular weight 2-3 times the average molecular weight between
      entanglements and a moderate cross-link density are sufficient to create a closed
      network structure with a high ligand density and a small average distance between
      them.

PMID- 21170902
TI  - Summary ROC curve based on a weighted Youden index for selecting an optimal
      cutpoint in meta-analysis of diagnostic accuracy.
AB  - Established approaches for analyzing meta-analyses of diagnostic accuracy model
      the bivariate distribution of the observed pairs of specificity Sp and
      sensitivity Se, thus accounting for across-study correlation. However, it is
      still a matter of debate how to define a summary ROC (SROC) curve. It was
      recently pointed out that the SROC curve is in principle unidentifiable if only
      one (Sp, Se) pair per study is known. We evaluate an alternative approach,
      modeling the study-specific ROC curves based on the assumption of linearity in
      logit space. A setting is considered in which the pair (Sp, Se) that is selected
      for publication in a particular study maximizes a weighted Youden index
      lambdaSe+(1-lambda)Sp with a given weight lambda.This leads to a fixed slope (1
      lambda)/lambda of the ROC curve in (1-Sp, Se), equivalent to a slope of (1
      lambda)Sp(1-Sp)/(lambdaSe(1-Se)) for the corresponding straight line in logit
      space. While the slope depends on the variance ratio of the underlying
      distributions, the intercept is a function of the mean difference. Our approach
      leads in a natural way to a new, model-based proposal for a summary ROC curve. It
      is illustrated using an example from the literature.

PMID- 21170901
TI  - Expanding colorectal cancer screening among minority women.
AB  - BACKGROUND: Colorectal cancer screening (CRCS) in the United States is inadequate
      in minority communities and particularly among those who lack insurance. Finding
      ways to increase screenings in these minorities presents a healthcare challenge.
      The authors sought to determine whether offering CRCS at the time of mammography
      is an effective way to increase CRCS among minority women. METHODS: This study
      was offered to women attending the Breast Examination Center of Harlem (BECH), a
      community outreach program of Memorial Sloan-Kettering serving the primarily
      black and Hispanic Harlem Community. Screening was explained, medical fitness was
      determined, and colonoscopies were performed. Barriers to screening and ways to
      overcome them were ascertained. Participants had to be at least 50 years of age
      without a history of colorectal cancer or screening within the last 10 years.
      RESULTS: There were 2616 women eligible for CRCS, of these women 2005 (77%)
      refused to participate in the study, and 611 (23%) women were enrolled. There was
      a high interest in CRCS including among those who declined to participate in the
      study. The major barrier was lack of medical insurance, which was partially
      overcome by alternative funding. Of the 611 women enrolled, 337 (55%) went on to
      have screening colonoscopy. Forty-nine (15%) women had adenomatous polyps.
      CONCLUSIONS: Offering CRCS to minority women at the time of mammography and
      without a physician's referral is an effective way to expand screening. Screening
      colonoscopy findings are similar to those in the general population. Alternatives
      to traditional medical insurance are needed for the uninsured.

PMID- 21170903
TI  - Time-dependent ROC analysis for a three-class prognostic with application to
      kidney transplantation.
AB  - The medical decision-making community has an extensive literature on the use of
      receiver operating characteristic (ROC) graphs for diagnostic testing.
      Heagertybiet al. have recently developed this ROC curve theory within the context
      of survival data (Biometrics 2000; 56:337-344). The time-dependent ROC method
      allows evaluating the accuracy of a marker to predict a time-dependent failure,
      whereas the classic methodology focuses on diagnosis. One limitation to this
      approach, however, is to analyse a single failure. In many medical situations, a
      marker can be useful to predict different competitive failures. For example in
      kidney transplantation, the terminal evolution can be a return to dialysis or the
      death of the patient. With this application in mind, our paper proposes an
      extension of the time-dependent ROC method for analysing the accuracy of a marker
      to predict two competitive events.

PMID- 21170904
TI  - Meta-analysis of diagnostic test data: a bivariate Bayesian modeling approach.
AB  - In the last decades, the amount of published results on clinical diagnostic tests
      has expanded very rapidly. The counterpart to this development has been the
      formal evaluation and synthesis of diagnostic results. However, published results
      present substantial heterogeneity and they can be regarded as so far removed from
      the classical domain of meta-analysis, that they can provide a rather severe test
      of classical statistical methods. Recently, bivariate random effects meta
      analytic methods, which model the pairs of sensitivities and specificities, have
      been presented from the classical point of view. In this work a bivariate
      Bayesian modeling approach is presented. This approach substantially extends the
      scope of classical bivariate methods by allowing the structural distribution of
      the random effects to depend on multiple sources of variability. Meta-analysis is
      summarized by the predictive posterior distributions for sensitivity and
      specificity. This new approach allows, also, to perform substantial model
      checking, model diagnostic and model selection. Statistical computations are
      implemented in the public domain statistical software (WinBUGS and R) and
      illustrated with real data examples.

PMID- 21170905
TI  - Correcting for misclassification for a monotone disease process with an
      application in dental research.
AB  - Motivated by a longitudinal oral health study, we evaluate the performance of
      binary Markov models in which the response variable is subject to an
      unconstrained misclassification process and follows a monotone or progressive
      behavior. Theoretical and empirical arguments show that the simple version of the
      model can be used to estimate the prevalence, incidences, and misclassification
      parameters without the need of external information and that the incidence
      estimators associated with the model outperformed approaches previously proposed
      in the literature. We propose an extension of the simple version of the binary
      Markov model to describe the relationship between the covariates and the
      prevalence and incidence allowing for different classifiers. We implemented a
      Bayesian version of the extended model and show that, under the settings of our
      motivating example, the parameters can be estimated without any external
      information. Finally, the analyses of the motivating problem are presented.

PMID- 21170906
TI  - An exact method for analysis following a two-stage phase II cancer clinical
      trial.
AB  - This paper presents an exact method for the analysis of a phase II cancer
      clinical trial conducted using a two-stage design in which early stopping may be
      allowed for either futility or efficacy. The method provides a point and interval
      estimate of the response probability associated with the treatment under
      investigation and a p-value for testing whether this exceeds some standard null
      value. Two-stage designs are often used in phase II trials in oncology for
      reasons of ethics and efficiency, but this design feature is seldom taken into
      account when the results are analyzed. After any two-stage design or multi-stage
      design, the method for analysis should take into account the previous interim
      analyses performed, otherwise the results will be biased. In this paper, an
      approximate approach based on a log-odds ratio parameterisation will be compared
      with an exact method through the calculation of the precise coverage
      probabilities of each approach.

PMID- 21170907
TI  - Confounder-adjusted estimates of the risk difference using propensity score-based
      weighting.
AB  - Confounder-adjusted estimates of the risk difference are often difficult to
      obtain by direct regression adjustment. Estimates can be obtained from a
      propensity score-based method using inverse probability-of-exposure weights to
      balance groups defined by exposure status with respect to confounders. Simulation
      was used to evaluate the performance of this method. The simulation model
      incorporated a binary confounder and a normally distributed confounder into
      logistic models of exposure status, and disease status conditional on exposure
      status. Data were generated for combinations of values of several design
      parameters, including the odds ratio relating each of the confounders to exposure
      status, the odds ratio relating each of the confounders to disease status and the
      total sample size. For most design parameter combinations (474 of 486), the
      absolute bias in the estimated risk difference was less than 1 percentage point,
      and it was never greater than 3 percentage points. The confidence interval
      generally had close to nominal 95 per cent coverage, but was prone to poor
      coverage levels (as low as 78.5 per cent) when both the confounder-to-exposure
      and confounder-to-outcome odds ratios were 5, consistent with strong confounding.
      The simulation results showed that the conditions that are favourable for good
      performance of the weighting method are: reasonable overlap in the propensity
      score distributions of the exposed and non-exposed groups and a large sample
      size.

PMID- 21170908
TI  - Robust non-parametric one-sample tests for the analysis of recurrent events.
AB  - One-sample non-parametric tests are proposed here for inference on recurring
      events. The focus is on the marginal mean function of events and the basis for
      inference is the standardized distance between the observed and the expected
      number of events under a specified reference rate. Different weights are
      considered in order to account for various types of alternative hypotheses on the
      mean function of the recurrent events process. A robust version and a stratified
      version of the test are also proposed. The performance of these tests was
      investigated through simulation studies under various underlying event generation
      processes, such as homogeneous and nonhomogeneous Poisson processes,
      autoregressive and renewal processes, with and without frailty effects. The
      robust versions of the test have been shown to be suitable in a wide variety of
      event generating processes. The motivating context is a study on gene therapy in
      a very rare immunodeficiency in children, where a major end-point is the
      recurrence of severe infections. Robust non-parametric one-sample tests for
      recurrent events can be useful to assess efficacy and especially safety in non
      randomized studies or in epidemiological studies for comparison with a standard
      population.

PMID- 21170909
TI  - A semiparametric estimator of survival for doubly truncated data.
AB  - Doubly truncated data are often encountered in the analysis of survival times,
      when the sample reduces to those individuals with terminating event falling on a
      given observational window. In this paper we assume that some information about
      the bivariate distribution function (df) of the truncation times is available.
      More specifically, we represent this information by means of a parametric model
      for the joint df of the truncation times. Under this assumption, a new
      semiparametric estimator of the lifetime df is derived. We obtain asymptotic
      results for the new estimator, and we show in simulations that it may be more
      efficient than the Efron-Petrosian nonparametric maximum likelihood estimator.
      Data on the age at diagnosis of childhood cancer in North Portugal are analyzed
      with the new method.

PMID- 21170910
TI  - An application of Harrell's C-index to PH frailty models.
AB  - Frailty models are encountered in many medical applications, yet little research
      has been devoted to develop measures that quantify the predictive ability of
      these models. In this paper, we elaborate on the concept of the concordance
      probability to clustered data, resulting in an 'Overall Conditional C-index' or
      bfC(O, C) and an 'Overall Marginal C-index' or C(O, M) . Both Overall C-indices
      can be split up into a 'Between Conditional' or C(B, C) and a 'Between Marginal C
      index' or C(B, M) and into a 'Within Conditional' or C(W, C) and a 'Within
      Marginal C-index' or C(W, M) . For PH frailty models of the power variance
      family, C(W, C) and C(W, M) are equivalent resulting in one 'Within C-index' C(W)
      . We propose an application of Harrell's C-index to estimate the proposed indices
      within a likelihood and a Bayesian context and the performances of their point
      estimates and confidence/credible intervals are compared in an extensive
      simulation study. This simulation study shows that the point estimates of C(W)
      and C(B, M) perform good within both a likelihood and Bayesian context but that
      the point estimates of C(B, C) show less bias for the Bayesian approach than for
      the likelihood approach. The 95 per cent confidence/credible intervals also
      possess good coverage properties, given that the point estimates perform good.
      The performance of the C-indices is evaluated on a real data set.

PMID- 21170911
TI  - Modelling competing risks data with missing cause of failure.
AB  - When competing risks data arise, information on the actual cause of failure for
      some subjects might be missing. Therefore, a cause-specific proportional hazards
      model together with multiple imputation (MI) methods have been used to analyze
      such data. Modelling the cumulative incidence function is also of interest, and
      thus we investigate the proportional subdistribution hazards model (Fine and Gray
      model) together with MI methods as a modelling approach for competing risks data
      with missing cause of failure. Possible strategies for analyzing such data
      include the complete case analysis as well as an analysis where the missing
      causes are classified as an additional failure type. These approaches, however,
      may produce misleading results in clinical settings. In the present work we
      investigate the bias of the parameter estimates when fitting the Fine and Gray
      model in the above modelling approaches. We also apply the MI method and evaluate
      its comparative performance under various missing data scenarios. Results from
      simulation experiments showed that there is substantial bias in the estimates
      when fitting the Fine and Gray model with naive techniques for missing data,
      under missing at random cause of failure. Compared to those techniques the MI
      based method gave estimates with much smaller biases and coverage probabilities
      of 95 per cent confidence intervals closer to the nominal level. All three
      methods were also applied on real data modelling time to AIDS or non-AIDS cause
      of death in HIV-1 infected individuals.

PMID- 21170912
TI  - Inference on the rate ratio of recurrent events for the matched pairs design.
AB  - As statistical methods for testing the null hypothesis of no difference between
      two groups for the matched pairs design, the paired-t test, Wilcoxon signed rank
      sum test and McNemar test are well known. However, there is no simple test for
      the comparison of incidence rate of recurrent events. This paper proposes a
      simple statistical method and a sample size formula for the comparison of counts
      of recurrent events over a specified period of observation under the matched
      pairs design, where the subject-specific incidence of recurrent events is assumed
      to follow a time-homogeneous Poisson process. As a special case, the proposed
      method is found to be virtually equivalent in form to Mantel-Haenszel method for
      a common rate ratio among the set of stratified tables based on person-time data.
      The proposed methods are illustrated with the within-arm comparison of data from
      a clinical trial of 59 epileptics with baseline count data.

PMID- 21170914
TI  - Planning and analysis of cross-over trials in infertility.
AB  - The use of cross-over trials in investigating treatments for infertility is
      discussed. A simple possible approach to analyzing such trials using the Mantel
      Haenszel procedure is explained. A more flexible approach based on the normal
      binomial mixture model of Ezzet and Whitehead is examined. It is shown how this
      may be implemented in various statistical packages by applying it to two real
      examples of trials in infertility. An approach that may be used to compare
      designs via simulation is explained briefly. It is concluded that provided that
      cross-over trials in infertility are regarded as parallel group trials with extra
      information rather than as cross-over trials with missing information, their use
      may be more promising than that has previously been concluded.

PMID- 21170913
TI  - Estimating the distribution of the window period for recent HIV infections: a
      comparison of statistical methods.
AB  - In the past few years a number of antibody biomarkers have been developed to
      distinguish between recent and established Human Immunodeficiency Virus (HIV)
      infection. Typically, a specific threshold/cut-off of the biomarker is chosen,
      values below which are indicative of recent infections. Such biomarkers have
      attracted considerable interest as the basis for incidence estimation using a
      cross-sectional sample. An estimate of HIV incidence can be obtained from the
      prevalence of recent infection, as measured in the sample, and knowledge of the
      time spent in the recent infection state, known as the window period. However,
      such calculations are based on a number of assumptions concerning the
      distribution of the window period. We compare two statistical methods for
      estimating the mean and distribution of a window period using data on repeated
      measurements of an antibody biomarker from a cohort of HIV seroconverters. The
      methods account for the interval-censored nature of both the date of
      seroconversion and the date of crossing a specific threshold. We illustrate the
      methods using repeated measurements of the Avidity Index (AI) and make
      recommendations about the choice of threshold for this biomarker so that the
      resulting window period satisfies the assumptions for incidence estimation.

PMID- 21170915
TI  - The analysis of cross-over trials with baseline measurements.
AB  - The statistical power of cross-over trials can be increased by taking 'baseline'
      measurements of the outcome variable at the start of each treatment period.
      Analysis of covariance (ANCOVA), rather than analysis of change scores, takes
      best advantage of this. However, ANCOVA can give biased treatment effect
      estimates in observational studies with true baseline imbalance. While in truth
      balanced, chance baseline imbalance is possible in individual randomized cross
      over studies due to their typically small sample size. Although such chance
      imbalance does not cause biased estimation on average over repeated trials, this
      simulation study will aim to confirm the appropriateness of ANCOVA when faced
      with the analysis of data from an individual trial in which chance baseline
      imbalance is clearly apparent. Randomized cross-over trials were simulated,
      varying in sample size and the pattern and strength of correlation between
      repeated measures. Estimates from ANCOVA, change scores, and post-treatment
      difference were unbiased on average across each set of simulated data sets.
      ANCOVA and change scores could use baseline information to improve precision, but
      change scores could also reduce precision if baseline measures were
      uninformative. Change scores only were correlated with chance within-subject
      baseline imbalance. All three estimators could be correlated with chance between
      subjects imbalance in the first period baseline measurements, the strongest
      associations being with the post-treatment difference. Consistent results were
      obtained from a real data example. In conclusion, ANCOVA took best advantage of
      baseline measures to improve precision, and avoided bias in the widest set of
      circumstances with chance imbalance in those baseline measures.

PMID- 21170916
TI  - Frequentist performance of Bayesian inference with response-adaptive designs.
AB  - In controlled clinical trials, where minimizing treatment failures is crucial,
      response-adaptive designs are attractive competitors to 1:1 randomized designs
      for comparing the success rates phi(1) and phi(2) of two treatments. In these
      designs each new treatment assignment depends on previous outcomes through some
      predefined rule. Here Play-The-Winner (PW), Randomized Play-The-Winner (RPW),
      Drop-The-Loser, Generalized Drop-the-Loser and Doubly adaptive Biased Coin
      Designs are considered for new treatment assignments. As frequentist inference
      relies on complex sampling distributions in those designs, we investigate how
      Bayesian inference, based on two independent Beta prior distributions, performs
      from a frequentist point-of-view. Performance is assessed through coverage
      probabilities of interval estimation procedures, power and minimization of
      failure count. It is shown that Bayesian inference can be favorably compared to
      frequentist procedures where the latter are available. The power of response
      adaptive designs is generally very close to the power of 1:1 randomized design.
      However, failure count savings are generally small, except for the PW and Doubly
      adaptive Biased Coin designs in particular ranges of the true success rates. The
      RPW assignment rule has the worst performance, while PW, Generalized Drop-the
      Loser or Doubly adaptive Biased Coin Designs may outperform other designs
      depending on different particular ranges of the true success rates.

PMID- 21170917
TI  - Simultaneous confidence bounds for relative risks in multiple comparisons to
      control.
AB  - We discuss the construction of asymptotic simultaneous upper confidence limits
      that jointly bound relative risks formed by comparing several treatments to a
      control. Motivated by a vaccine study, we investigate the performance of several
      methods under such settings. Inverting the minimum of score statistics, together
      with estimating the correlation matrix of these statistics under the null gives
      simultaneous coverage rates closest to the nominal level. In typical settings of
      vaccine studies, this method proves to be the most powerful of the ones
      considered, but computationally simpler alternatives are also worth exploring
      when the number of comparisons is large. Simultaneous lower and two-sided
      confidence intervals are also considered. All procedures can be implemented and
      evaluated using freely available and general R code.

PMID- 21170918
TI  - Generalized pairwise comparisons of prioritized outcomes in the two-sample
      problem.
AB  - This paper extends the idea behind the U-statistic of the Wilcoxon-Mann-Whitney
      test to perform generalized pairwise comparisons between two groups of
      observations. The observations are outcomes captured by a single variable,
      possibly repeatedly measured, or by several variables of any type (e.g. discrete,
      continuous, time to event). When several outcomes are considered, they must be
      prioritized. We show that generalized pairwise comparisons extend well-known non
      parametric tests, and illustrate their interest using data from two randomized
      clinical trials. We also show that they lead to a general measure of the
      difference between the groups called the 'proportion in favor of treatment',
      denoted Delta, which is related to traditional measures of treatment effect for a
      single variable.

PMID- 21170919
TI  - Genetic analysis of age-at-onset traits based on case-control family data.
AB  - Family studies are a useful alternative to twin studies for disentangling genetic
      and environmental effects on human diseases. However, although age-at-onset
      traits are often of interest, family-based quantitative genetic analysis of such
      data is still not commonly used. One reason is that we need multiple random
      components to capture the genetic and environmental contributions, so it becomes
      hard to use the existing frailty models for correlated survival data. In this
      paper we consider the alternative accelerated failure-time models with random
      effects. The method allows both left truncation and right censoring, and it can
      deal with an arbitrary family structure and multiple random components. For
      estimation we use the h-likelihood procedure, which avoids the integration of the
      random effects in the marginal likelihood approach. To deal with large cohort
      data, we propose a case-control scheme, where we ascertain all families with at
      least two events and a subsample of control families. A pseudo-h-likelihood
      approach is used to analyse the ascertained data. We study the performance of the
      method using simulated data, and provide an illustration with analysis of
      melanoma in the Swedish population.

PMID- 21170920
TI  - Discriminant analysis using a multivariate linear mixed model with a normal
      mixture in the random effects distribution.
AB  - We have developed a method to longitudinally classify subjects into two or more
      prognostic groups using longitudinally observed values of markers related to the
      prognosis. We assume the availability of a training data set where the subjects'
      allocation into the prognostic group is known. The proposed method proceeds in
      two steps as described earlier in the literature. First, multivariate linear
      mixed models are fitted in each prognostic group from the training data set to
      model the dependence of markers on time and on possibly other covariates. Second,
      fitted mixed models are used to develop a discrimination rule for future
      subjects. Our method improves upon existing approaches by relaxing the normality
      assumption of random effects in the underlying mixed models. Namely, we assume a
      heteroscedastic multivariate normal mixture for random effects. Inference is
      performed in the Bayesian framework using the Markov chain Monte Carlo
      methodology. Software has been written for the proposed method and it is freely
      available. The methodology is applied to data from the Dutch Primary Biliary
      Cirrhosis Study.

PMID- 21170921
TI  - Multiple correspondence discriminant analysis: an application to detect
      stratification in copy number variation.
AB  - We illustrate the use of multiple correspondence analysis (MCA) to correct for
      population stratification of copy number alteration data. In addition, we propose
      the use of multiple correspondence discriminant analysis (MCDA) to identify an
      optimal set of copy number variants (CNVs) that correctly infers the population
      stratification of a CNV map. Within MCDA, we highlight the novel use of
      correlation with class directions for variable ranking. We found a set of 20 CNVs
      with 98 per cent predictability in a CNV map of the HapMap populations. On this
      sample, the selection of variables based on centroid ranking outperformed the
      most common practice of ranking variables with their correlation to the principal
      axes.

PMID- 21170922
TI  - Hurdle models for multilevel zero-inflated data via h-likelihood.
AB  - Count data often exhibit overdispersion. One type of overdispersion arises when
      there is an excess of zeros in comparison with the standard Poisson distribution.
      Zero-inflated Poisson and hurdle models have been proposed to perform a valid
      likelihood-based analysis to account for the surplus of zeros. Further, data
      often arise in clustered, longitudinal or multiple-membership settings. The
      proper analysis needs to reflect the design of a study. Typically random effects
      are used to account for dependencies in the data. We examine the h-likelihood
      estimation and inference framework for hurdle models with random effects for
      complex designs. We extend the h-likelihood procedures to fit hurdle models,
      thereby extending h-likelihood to truncated distributions. Two applications of
      the methodology are presented.

PMID- 21170923
TI  - Switching of ferroelectrics without domains.
AB  - A discussion of switching in polyvinyl difluoride copolymers is given (see L.
      Zhang, EPL 2010, 91, 47001) in terms of the general history of ferroelectric
      switching with and without domain wall participation.

PMID- 21170924
TI  - Flavonoids inhibit angiogenic cytokine production by human glioma cells.
AB  - VEGF and TGF-beta1 are cytokines that stimulate tissue invasion and angiogenesis.
      These factors are considered as molecular targets for the therapy of
      glioblastoma. Bevacizumab, a recombinant humanized monoclonal antibody developed
      against VEGF, inhibits endothelial cell proliferation and vessel formation.
      Flavonoids obtained from Dimorphandra mollis and Croton betulaster have been
      described as proliferation inhibitors of a human glioblastoma derived cell line.
      VEGF and TGF-beta1 levels were dosed by ELISA in a GL-15 cell line treated with
      bevacizumab and also with the flavonoids rutin, 5-hydroxy-7,4'-dimethoxyflavone,
      casticin, apigenin and penduletin. Rutin reduced the VEGF and TGF-beta1 levels
      after 24 h but not after 72 h. The other flavonoids significantly reduced TGF
      beta1 production. Bevacizumab reduced only the VEGF levels in the supernatant
      from GL-15 cultures. These results suggest that the flavonoids studied, and
      commonly used in popular medicine, present an interesting subject of study due to
      their potential effect as angiogenic factor inhibitors.

PMID- 21170925
TI  - Decursin and decursinol from Angelica gigas inhibit the lung metastasis of murine
      colon carcinoma.
AB  - The principal objective of the present study was to evaluate the antimetastatic
      activity of decursin and decursinol isolated from Angelica gigas. Decursin and
      decursinol inhibited the proliferation and invasion of CT-26 colon carcinoma
      cells. The expressions of matrix metalloproteinase (MMP)-2 and MMP-9 in cells and
      the activities in the culture medium were also reduced by decursin and decursinol
      treatment. In CT-26 cells, the extracellular signal-regulated kinase (ERK)
      inhibitor inhibited cell proliferation, invasion and MMP-9 expression, and the c
      Jun N-terminal kinase (JNK) inhibitor suppressed the expression of both MMPs, as
      well as cell proliferation and cell invasion. The phosphatidylinositol-3 kinase
      (PI3K) inhibitor reduced only the expression of MMP-2. In addition, the invasion
      of CT-26 cells was inhibited by the treatment with anti-MMP-9 antibody, rather
      than anti-MMP-2 antibody. These results indicate that MMP-9 expression via ERK
      and JNK plays a critical role for the invasion of CT26 cells. Decursin and
      decursinol downregulated ERK and JNK phosphorylation. Moreover, oral
      administration of decursin and decursinol reduced the formation of tumor nodules
      in the lungs and the increase in lung weight caused by CT-26 metastases.
      Therefore, both decursin and decursinol may be beneficial antimetastatic agents,
      targeting MMPs and their upstream signaling molecules.

PMID- 21170931
TI  - Journal of Biophotonics is growing up.

PMID- 21170927
TI  - Widely expressed Af17 is likely not required for embryogenesis, hematopoiesis,
      and animal survival.
AB  - As a putative transcription factor, Af17 may play a role in multiple signaling
      pathways. However, the Af17 expression profile during development and in adult
      tissues remains largely uncharacterized. The importance of Af17 function in
      embryogenesis, hematopoiesis, and animal survival has never been addressed
      before. Here we report the generation of the first Af17 mutant mouse model and
      characterization of the Af17 temporal and spatial expression profile in various
      embryonic stages and adult tissues by X-gal staining, in situ hybridization, and
      RT-PCR. Af17 expression is detected in specific cell populations in all stages
      and in multiple tissues examined. In situ hybridization yielded a consistent Af17
      expression pattern by X-gal staining. Homozygous mutant mice are viable, fertile,
      normal in size, and do not display any gross physical, behavioral, or
      hematopoietic abnormalities. Thus, our studies describe the generation of the
      first Af17 mutant mouse model, provide the first developmental profile of Af17
      expression, and reveal that Af17 may be dispensable for normal embryogenesis,
      hematopoiesis, and animal survival.

PMID- 21170937
TI  - Risks of papillary and follicular thyroid cancer among immigrants to Sweden.
AB  - Previous studies have indicated that ionizing radiation, particularly during
      childhood, is the main established risk factor for thyroid cancer. History of
      benign nodules/adenoma, goiter, iodine deficiency or high-iodine intake might be
      other associated factors. We wanted to define the histology-specific thyroid
      cancer risk in the first-generation immigrants to Sweden. We used the 2010 update
      of the nation-wide Swedish Family-Cancer Database (>12 million individuals; 1.8
      million immigrants; histology code in force since 1958) to calculate standardized
      incidence ratios (SIRs) for histology-specific thyroid cancer among immigrants
      compared to the native Swedes. The patient series covered 2,604 male and 6,406
      female Swedes, and 247 and 863 immigrants. The median age at immigration was 29
      years, and the median age at thyroid cancer diagnosis was 46 years. Increased
      risks for female papillary carcinoma were observed for Finns (SIR = 1.63), former
      Yugoslavians (2.36), Russians (2.34), other East Europeans (2.14), Turks (3.16),
      Iranians (2.68), Iraqis (2.77), East and Southeast Asians (2.92), other Asians
      (1.69) and South Americans (2.23). Male Iranians (2.85), East and Southeast
      Asians (3.57) and other Asians (2.26) had an increased risk for papillary
      carcinoma. Only male East and Southeast Asians (2.93) had an increased risk for
      follicular carcinoma. The data might suggest that immigrant populations in Sweden
      from areas of low or high-iodine intake are at risk of papillary carcinoma,
      implicating iodine imbalance as a contributing factor to our findings. The
      increased risk of thyroid cancer among Asian immigrants may confirm the role of
      childhood-ionizing radiation on thyroid cancer risk.

PMID- 21170936
TI  - Butein, a tetrahydroxychalcone, suppresses cancer-induced osteoclastogenesis
      through inhibition of receptor activator of nuclear factor-kappaB ligand
      signaling.
AB  - Osteoclastogenesis is associated with aging and various age-related inflammatory
      chronic diseases, including cancer. Receptor activator of nuclear factor-kappaB
      (NF-kappaB) ligand (RANKL), a member of the tumor necrosis factor superfamily,
      has been implicated as a major mediator of bone resorption, suggesting that
      agents that can suppress RANKL signaling might inhibit osteoclastogenesis, a
      process closely linked to bone resorption. We therefore investigated whether
      butein, a tetrahydroxychalcone, could inhibit RANKL signaling and suppress
      osteoclastogenesis induced by RANKL or tumor cells. We found that human multiple
      myeloma cells (MM.1S and U266), breast tumor cells (MDA-MB-231) and prostate
      tumor cells (PC-3) induced differentiation of macrophages to osteoclasts, as
      indicated by tartrate-resistant acid phosphatase (TRAP)-positive cells, and that
      butein suppressed this process. The chalcone also suppressed the expression of
      RANKL by the tumor cells. We further found that butein suppressed RANKL-induced
      NF-kappaB activation and that this suppression correlated with the inhibition of
      IkappaBalpha kinase and suppression of phosphorylation and degradation of
      IkappaBalpha, an inhibitor of NF-kappaB. Finally, butein also suppressed the
      RANKL-induced differentiation of macrophages to osteoclasts in a dose-dependent
      and time-dependent manner. Collectively, our results indicate that butein
      suppresses the osteoclastogenesis induced by tumor cells and by RANKL, by
      suppression of the NF-kappaB activation pathway.

PMID- 21170950
TI  - Retraction: Lanthanide-alkali metal sandwich complexes: synthesis, structure, and
      solvent-mediated redox transformations, and one-dimensional frameworks assembled
      through cation-arene pi interactions.

PMID- 21170951
TI  - Retraction: Ultrahighly sensitive homogeneous detection of DNA and microRNA by
      using single-silver-nanoparticle counting.

PMID- 21170955
TI  - Loss of white matter integrity in major depressive disorder: evidence using tract
      based spatial statistical analysis of diffusion tensor imaging.
AB  - White matter (WM) has been shown to be affected in elderly patients with major
      depressive disorders (MDD). There is only limited evidence of WM structural
      abnormalities in nongeriatric MDD patients. This study investigates WM
      microstructural integrity in nongeriatric MDD patients recruited as part of the
      International Study to Predict Optimized Treatment in Depression clinical trial
      and establishes the validity of diffusion tensor imaging measures for the
      investigation of depression. Baseline diffusion tensor imaging data from 29
      nongeriatric MDD participants (11 with melancholia) and 39 healthy control
      participants were used in this analysis. We performed tract-based spatial
      statistics analyses to evaluate WM microstructural integrity (1) between all
      healthy controls and all MDD participants, (2) between melancholic and
      nonmelancholic MDD participants, and (3) between each subgroup (melancholic and
      nonmelancholic) and controls. Significant WM integrity deficits were seen only
      for the melancholic MDD participants compared with controls. Compared with
      controls, melancholic participants showed an average reduction of 7.8% in
      fractional anisotropy over WM regions associated with the limbic system,
      dorsolateral prefrontal cortex, thalamic projection fibers, corpus callosum, and
      other association fibers. These fractional anisotropy deficits were also
      associated with decreased axial and increased radial diffusivity in these WM
      regions, suggesting a pattern of decreased myelination or other degeneration
      change. Our findings of WM structural abnormalities associated with the limbic
      system, the frontal cortex, and the thalamus support the prevailing theory of
      limbic-dorsolateral prefrontal cortex-thalamic dysfunction in depression. Our
      results also suggest that these deficits are most prominent in the melancholic
      subtype of MDD.

PMID- 21170956
TI  - Localization of cerebral functional deficits in patients with non
      neuropsychiatric systemic lupus erythematosus.
AB  - Neuropsychiatric systemic lupus erythematosus (NP-SLE) is a common complication
      of systemic lupus erythematosus (SLE), and clinical interventions are of only
      limited efficacy despite relatively high prevalence. Such complications have been
      studied extensively, but the pathoetiology of NP-SLE has not yet been elucidated.
      Diagnosis of NP-SLE focuses primarily on psychological manifestations, and the
      underlying mechanisms leading to neuropsychiatric complications remain unknown.
      To address potential changes in brain function before NP-SLE development, we used
      resting-state functional magnetic resonance imaging (MRI) to compare regional
      brain activity in SLE patients versus matched controls. We report that regional
      activity in cerebellum and in areas of the default mode network are attenuated in
      patients with SLE, and moreover individual alterations in cerebellar activity
      correlated positively with the disease activity index. These findings provide
      direct evidence that significant alteration of brain function, resembling that
      observed in patients with NP-SLE, is already present in SLE patients without
      neuropsychiatric complications, highlighting the need for early evaluation and
      intervention in SLE patients. Furthermore, the disease activity rating correlated
      with regional functional alterations in the cerebellum, suggesting that the
      cerebellum could play a role in the pathogenesis of NP-SLE.

PMID- 21170957
TI  - Lack of ex vivo peripheral and intrahepatic alpha-fetoprotein-specific CD4+
      responses in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies with a poor
      prognosis and limited therapeutic options that is often characterized by the
      expression of the tumor-associated antigen alpha-fetoprotein (AFP). CD4+ helper T
      cells are important in generating potent anticancer immunity as they prime and
      expand CD8+ T-cell memory and may also have direct antitumor activity. However,
      very little information is currently available about the relative frequency,
      immunodominance and peripheral versus intratumoral distribution of AFP-specific
      CD4+ T-cell responses in patients with HCC. We, therefore, analyzed AFP-specific
      CD4+ responses in blood and tumor tissue of patients with HCC by using
      overlapping peptides spanning the entire AFP protein and novel sensitive
      approaches such as antigen-specific upregulation of CD154. We found that AFP
      specific CD4+ T-cell responses were not detectable in the peripheral blood ex
      vivo. However, after in vitro stimulation, AFP-specific CD4+ T-cell responses
      were detectable in a large fraction of patients targeting different previously
      unreported epitopes with no clear immunodominance. These results indicate that
      AFP-specific CD4+ T-cell responses are not completely deleted but only present at
      very low frequencies. Importantly, AFP-specific CD4+ T-cell responses were also
      rarely detectable in tumor tissue, suggesting that the relative absence of these
      cells in the circulation ex vivo is not due to a rapid accumulation to the tumor
      side. Taken together, these results suggest that the lack of sufficient CD4+ T
      cell help, especially within the tumor tissue, may be one central mechanism
      responsible for the failure of AFP-specific immune responses to control HCC
      progression.

PMID- 21170958
TI  - 5-Aza-2'-deoxycytidine and interleukin-1 cooperate to regulate matrix
      metalloproteinase-3 gene expression.
AB  - Members of the matrix metalloproteinase (MMP) family of enzymes play a critical
      role in extracellular matrix remodeling in a number of normal and pathologic
      processes. Accordingly, activation of MMP gene expression is tightly regulated at
      the level of transcription by specific transcription factors, most notably
      following exposure to inflammatory cytokines. Recent studies with 5-aza-2'
      deoxycytidine (5-aza-dC), a specific DNA methylase inhibitor, also suggest that
      epigenetic processes contribute to the regulation of MMP expression. Although
      inflammation-related aberrant patterns of DNA methylation have been described, a
      mechanistic link between inflammation and epigenetic alterations in the control
      of MMP expression remains unclear. Here, we provide evidence that increased MMP-3
      expression by 5-aza-dC is modulated by interleukin-1 (IL-1). More specifically,
      we found that stimulation with IL-1, but not with IL-6 or TNFalpha, significantly
      increased the hypomethylation status of the MMP-3 promoter to a level similar to
      that found in dnmt1/dnmt3b-deficient HCT116 (DKO) cells. Furthermore, we showed
      that increased MMP-3 expression by 5-aza-dC was associated with increased
      expression and activity of specific transcription factors known to regulate MMP-3
      expression. In fact, treatment with 5-aza-dC was obligatory for some
      transcription factors to trigger an increase in MMP-3 expression, such as Ap-1.
      In contrast, CCAAT enhancer-binding proteins and E-twenty six were capable of
      inducing MMP-3 alone. Overall, these findings provide a novel perspective of the
      collaborative role of 5-aza-dC and inflammatory cytokines with specific
      transcription factors that are normally involved in MMP-3 expression.

PMID- 21170960
TI  - Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic,
      stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor
      activity.
AB  - Angiogenesis, a critical driver of tumor development, is controlled by
      interconnected signaling pathways. Vascular endothelial growth factor receptor
      (VEGFR) 2 and tyrosine kinase with immunoglobulin and epidermal growth factor
      homology domain 2 play crucial roles in the biology of normal and tumor
      vasculature. Regorafenib (BAY 73-4506), a novel oral multikinase inhibitor,
      potently inhibits these endothelial cell kinases in biochemical and cellular
      kinase phosphorylation assays. Furthermore, regorafenib inhibits additional
      angiogenic kinases (VEGFR1/3, platelet-derived growth factor receptor-beta and
      fibroblast growth factor receptor 1) and the mutant oncogenic kinases KIT, RET
      and B-RAF. The antiangiogenic effect of regorafenib was demonstrated in vivo by
      dynamic contrast-enhanced magnetic resonance imaging. Regorafenib administered
      once orally at 10 mg/kg significantly decreased the extravasation of Gadomer in
      the vasculature of rat GS9L glioblastoma tumor xenografts. In a daily (qd)*4
      dosing study, the pharmacodynamic effects persisted for 48 hr after the last
      dosing and correlated with tumor growth inhibition (TGI). A significant reduction
      in tumor microvessel area was observed in a human colorectal xenograft after qd*5
      dosing at 10 and 30 mg/kg. Regorafenib exhibited potent dose-dependent TGI in
      various preclinical human xenograft models in mice, with tumor shrinkages
      observed in breast MDA-MB-231 and renal 786-O carcinoma models. Pharmacodynamic
      analyses of the breast model revealed strong reduction in staining of
      proliferation marker Ki-67 and phosphorylated extracellular regulated kinases
      1/2. These data demonstrate that regorafenib is a well-tolerated, orally active
      multikinase inhibitor with a distinct target profile that may have therapeutic
      benefit in human malignancies.

PMID- 21170962
TI  - Childhood Hodgkin's lymphoma, non-Hodgkin's lymphoma and factors related to the
      immune system: the Escale Study (SFCE).
AB  - The study investigated the role of factors considered related to the early
      stimulation of the immune system in the aetiology of childhood lymphoma. The
      national registry-based case-control study, Escale, was carried out in France
      over the period 2003-2004. Population controls were frequency matched with the
      cases on age and gender. Data were obtained from structured telephone
      questionnaires administered to mothers. Odds ratios (ORs) were estimated using
      unconditional regression models adjusted for potential confounders. Data from 128
      cases of Hodgkin's lymphoma (HL) aged 5-14 years, 164 cases of non-Hodgkin's
      lymphoma (NHL) aged 2-14 years and 1,312 controls were analyzed. Negative
      associations were observed between HL and day care attendance [OR = 0.5 (0.2
      1.2)] and between HL and repeated early common infections among non-breastfed
      children [OR = 0.3 (.2-0.7), p = 0.003] [OR for breastfed children: 1.0 (.5
      2.1)], but not for the other factors investigated. Negative associations were
      observed between NHL and birth order 3 or more [OR = 0.7 (0.4-1.1)], prolonged
      breastfeeding [OR = 0.5 (0.3-1.0)], regular contact with farm animals [OR = 0.5
      (0.3-1.0)], frequent farm visits in early life [OR = 0.6 (0.4-1.1)] and history
      of asthma [OR = 0.6 (0.3-1.1)]. In conclusion, the results partly support the
      hypothesis that an abnormal maturation of the immune system may play a role in
      childhood HL or NHL, and call for further investigations.

PMID- 21170961
TI  - Sunitinib facilitates the activation and recruitment of therapeutic anti-tumor
      immunity in concert with specific vaccination.
AB  - The multikinase inhibitor sunitinib malate (SUT) has been reported to reduce
      levels of myeloid suppressor cells and Treg cells in cancer patients,
      hypothetically diminishing intrinsic impediments for active immunization against
      tumor-associated antigens in such individuals. The goal of this study was to
      identify longitudinal immune molecular and cellular changes associated with tumor
      regression and disease-free status after the treatment of established day 7 s.c.
      MO5 (B16.OVA) melanomas with SUT alone (1 mg/day via oral gavage for 7 days),
      vaccination using ovalbumin (OVA) peptide-pulsed dendritic cell [vaccine (VAC)]
      alone, or the combination of SUT and VAC (SUT/VAC). We observed superior anti
      tumor efficacy for SUT/VAC combination approaches, particularly when SUT was
      applied at the time of the initial vaccination or the VAC boost. Treatment
      effectiveness was associated with the acute loss of (and/or failure to recruit)
      cells bearing myeloid-derived suppressor cells or Treg phenotypes within the
      tumor microenvironment (TME) and the corollary, prolonged enhancement of Type-1
      anti-OVA CD8(+) T cell responses in the tumor-draining lymph node and the TME.
      Enhanced Type-1 T cell infiltration of tumors was associated with treatment
      induced expression of vascular cell adhesion molecule-1 (VCAM-1) and CXCR3 ligand
      chemokines in vascular/peri-vascular cells within the TME, with SUT/VAC therapy
      benefits conditionally negated upon adminsitration of CXCR3 or VCAM-1 blocking
      antibodies. These data support the ability of a short 7 day course of SUT to
      (re)condition the TME to become more receptive to the recruitment and prolonged
      therapeutic action of (VAC-induced) anti-tumor Tc1 cells.

PMID- 21170963
TI  - Serum level of adiponectin and the risk of liver cancer development in chronic
      hepatitis C patients.
AB  - Obesity and metabolic syndrome are recognized risk factors for development of
      hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC).
      Dysregulation of adipokines, particularly the decreased secretion of adiponectin,
      appears to play a key role. To investigate the association between adiponectin
      and hepatocarcinogenesis, we conducted a large-scale retrospective cohort study.
      We enrolled 325 patients with CHC (146 men, 179 women; mean age 58.0 +/- 10.3
      years) whose serum samples were collected between January 1994 and December 2002.
      Subjects were divided into two groups according to their serum adiponectin
      levels. We evaluated the association between adiponectin level and the risk of
      subsequent HCC development using univariate and multivariate Cox proportional
      hazard regression. Because average serum adiponectin level was higher in females
      than males, each gender was analyzed separately. Patients with CHC had
      significantly higher adiponectin levels than healthy controls. During the follow
      up period (mean: 9.0 years), HCC developed in 122 subjects. Unexpectedly,
      subjects with higher serum adiponectin levels had a higher incidence of HCC
      (males: p = 0.032; females: p = 0.01; log-rank test). Multivariate analysis
      revealed that a high serum adiponectin level was independently associated with
      HCC development (hazard ratio [HR] = 2.07; p = 0.031 in females and HR = 1.82; p
      = 0.05 in males). Isoform analysis revealed that middle- and low-molecular-weight
      isoforms contributed to the risk of HCC. In conclusion, Patients who had CHC with
      high serum adiponectin levels had a higher risk of liver cancer development.
      Adiponectin may thus be tumorigenic or indicate a liver disease state
      independently of other clinical parameters.

PMID- 21170978
TI  - Antimicrobial organophilic montmorillonite nanoparticles: screening and detection
      assay.
AB  - The present study presents the development of a standard protocol for detection
      and screening of nanoparticle(s) for their antimicrobial activity with particular
      reference to organophilic montmorillonite (Ommt). For this purpose, Ommt
      nanoparticles have been synthesized through cation exchange of commercial
      montmorillonite (K10) with a cetyl pyridinium bromide. The formation of Ommt has
      been ascertained through UV-visible, Fourier transform infrared spectroscopy, X
      ray diffraction spectra, and transmission electron microscopy. Subsequently,
      "zone of inhibition" and "bacterial killing" assays were performed by incubating
      the four Gram-negative test bacteria with Ommt, to determine antimicrobial
      activity and reduction in colony forming unit per mL (confirmative test),
      respectively. The developed assay will provide an easy approach over conventional
      disc diffusion antibiotic sensitivity test, to study the impact of different
      nanoparticles against different bacterial species.

PMID- 21170979
TI  - Conjugation of enzymes on RNA probes through Cu(I) catalyzed alkyne-azide
      cycloaddition.
AB  - Northern and Southern blots are the most commonly used techniques for the
      confirmation of presence and expression of target genes. Molecular tools
      available for this purpose include radioisotope-, enzyme- and hapten-labeled
      nucleic acid probes. In particular, the use of enzyme-labeled probes are easy and
      safe, and do not require bound/free processes after hybridization associated with
      an antibody-based detection system. However, there are few approaches that enable
      the post-transcriptional modification of RNA with enzymes or proteins. In this
      study, we applied the Cu(I)-catalyzed [3 + 2] azide-alkyne cycloaddition (CuAAC)
      reaction to the labeling of an RNA strand with enzymes. The C-5 position of UTP
      was modified with an alkyne group and alkyne-bearing RNA was prepared by in vitro
      transcription using T7 RNA polymerase. Surface amino groups of bacterial alkaline
      phosphatase (BAP) were randomly derivatized with azide groups at different
      modification ratios. The CuAAC reaction occurred selectively between the alkyne
      modified RNA and the azide-modified enzyme. The RNA probe conjugated with BAP
      using this technique could detect a specific RNA by dot blot northern
      hybridization.

PMID- 21170980
TI  - A single-use purification process for the production of a monoclonal antibody
      produced in a PER.C6 human cell line.
AB  - Advances in single-use technologies can enable greater speed, flexibility, and a
      smaller footprint for multi-product production facilities, such as at a contract
      manufacturer. Recent efforts in the area of cell line and media optimization have
      resulted in bioreactor productivities that exceed 8 g/L in fed-batch processes or
      25 g/L in high-density cell culture processes. In combination with the
      development of single-use stirred tank bioreactors with larger working volumes,
      these intensified upstream processes can now be fit into a single-use
      manufacturing setting. Contrary to these upstream advances, downstream single-use
      technologies have been slower to follow, mostly limited by low capacity, high
      cost, and poor scalability. In this study we describe a downstream process based
      solely on single-use technologies that meets the challenges posed by expression
      of a mAb (IgG(1)) in a high-density suspension culture of PER.C6 cells. The cell
      culture harvest was clarified by enhanced cell settling (ECS) and depth
      filtration. Precipitation was used for crude purification of the mAb. A high
      capacity chromatographic membrane was then used in bind/elute mode, followed by
      two membranes in flow-through (FT) mode for polishing. A proof of concept of the
      entire disposable process was completed for two different scales of the
      purification train.

PMID- 21170982
TI  - Targeted protein pullout from human tissue samples using competitive elution.
AB  - One commonly used strategy to gain information on the proteins in a cell is to
      isolate the proteins of interest by specific binders, often antibodies. Not only
      the specificity of the capturing antibodies but also the washing and elution
      conditions are crucial to avoid false-positive protein identifications. Eluting
      the target protein from the matrix, while avoiding the release of unrelated
      background proteins, should both provide more correct information on the target
      protein and its interaction partners, and minimize the effort to perform
      downstream analyses through the reduced number of eluted proteins. In this study,
      a novel approach for selective protein pullout is presented. Monospecific
      antibodies were used to selectively pullout target proteins from a complex
      biosample. Subsequently, the target proteins were competitively eluted from the
      affinity media with the recombinant antigen. To deplete the antigen from the
      eluted sample, IMAC spin columns were utilized to bind the N-terminal His-tag of
      the antigens. The competitive elution method was applied both to a model system,
      and for the extraction of a native human target protein. In the model system the
      recombinant target protein BBC7 was spiked into a protein extract of human liver,
      whereas an endogenously expressed target protein, cTAGE5, was extracted from the
      liver extract directly. SDS-PAGE analysis and mass spectrometry confirmed
      affinity isolation of expected target proteins. More selective elution was
      obtained using the competitive procedure as compared to elution at low pH.
      Competitive elution has thus been shown to offer an effective approach for wide
      scale pullout experiments where proteins and their interaction partners are to be
      studied.

PMID- 21170983
TI  - Recombinant antibodies: engineering and production in yeast and bacterial hosts.
AB  - After the appearance of the first FDA-approved antibody 25 years ago, antibodies
      have become major therapeutic agents in the treatment of many human diseases,
      including cancer and infectious diseases, and the use of antibodies as
      therapeutic/diagnostic agents is expected to increase in the future. So far, a
      variety of strategies have been devised for engineering of these fascinating
      molecules to develop superior properties and functions. Recent progress in
      systems biology has provided more information about the structures and cellular
      networks of antibodies, and, in addition, recent development of biotechnology
      tools, particularly in regard to high-throughput screening, has made it possible
      to perform more intensive engineering on these substances. Based on a sound
      understanding and new technologies, antibodies are now being developed as more
      powerful drugs. In this review, we highlight the recent, significant progress
      that has been made in antibody engineering, with a particular focus on Fc
      engineering and glycoengineering for improved functions, and cellular engineering
      for enhanced production of antibodies in yeast and bacterial hosts.

PMID- 21170988
TI  - Bortezomib induces apoptosis in T lymphoma cells and natural killer lymphoma
      cells independent of Epstein-Barr virus infection.
AB  - Epstein-Barr virus (EBV), which infects not only B cells, but also T cells and
      natural killer (NK) cells, is associated with multiple lymphoid malignancies.
      Recently, the proteasome inhibitor bortezomib was reported to induce apoptosis of
      EBV-transformed B cells. We evaluated the killing effect of this proteasome
      inhibitor on EBV-associated T lymphoma cells and NK lymphoma cells. First, we
      found that bortezomib treatment decreased the viability of multiple T and NK cell
      lines. No significant difference was observed between EBV-positive and EBV
      negative cell lines. The decreased viability in response to bortezomib treatment
      was abrogated by a pan-caspase inhibitor. The induction of apoptosis was
      confirmed by flow cytometric assessment of annexin V staining. Additionally,
      cleavage of caspases and polyadenosine diphosphate-ribose polymerase, increased
      expression of phosphorylated IkappaB, and decreased expression of inhibitor of
      apoptotic proteins were detected by immunoblotting in bortezomib-treated cell
      lines. We found that bortezomib induced lytic infection in EBV-positive T cell
      lines, although the existence of EBV did not modulate the killing effect of
      bortezomib. Finally, we administered bortezomib to peripheral blood mononuclear
      cells from five patients with EBV-associated lymphoproliferative diseases.
      Bortezomib had a greater killing effect on EBV-infected cells. These results
      indicate that bortezomib killed T or NK lymphoma cells by inducing apoptosis,
      regardless of the presence or absence of EBV.

PMID- 21170987
TI  - Polo-like kinase 1 regulates cell proliferation and is targeted by miR-593* in
      esophageal cancer.
AB  - Polo-like kinase 1 (PLK1) is overexpressed in various human cancers. However, the
      biological functions and the post-transcriptional regulations of PLK1 in
      esophageal cancer (EC) are still unknown. The purposes of our study are to
      determine whether PLK1 can be a molecular target of EC therapy and to identify a
      microRNA (miRNA) targeting PLK1. We performed loss-of-function and gain-of
      function experiments regarding cell proliferation, cell cycle, apoptosis, in vivo
      tumor formation and luciferase reporter assays, using siRNAs against PLK1 and
      miRNA. PLK1 protein was expressed in all 11 EC cell lines, but not in normal
      esophageal epithelial cells (HEEpiC). Knockdown of PLK1 in EC cells induced G2/M
      arrest (p < 0.001) in cell cycle assay and reduced cell proliferation (p = 0.019)
      and tumor formation ability in vivo (p < 0.0001). MiR-593*, identified as a miRNA
      targeting PLK1 by a database search, was less expressed especially in six EC cell
      lines than HEEpiC cells. Moreover, miR-593* expression level was inversely
      correlated with PLK1 mRNA level in 48 clinical tissue specimens of EC (p =
      0.006). Introduction of synthetic miR-593* suppressed PLK1 expression by 69-73%,
      reduced cell proliferation (p = 0.008) and increased cell proportion of G2/M
      phase (p = 0.01) in HSA/c (an EC cells), whereas a miR-593* inhibitor upregulated
      PLK1 expression by 11-55%. Additionally, luciferase assay demonstrated that miR
      593* interacted two binding sites in the PLK1 3'-UTR and reduced 56.8-71.5% of
      luciferase activity by degrading luciferase mRNA in HSA/c cells. In conclusion,
      PLK1 is post-transcriptionally regulated by miR-593* and could be a promising
      molecular target for EC treatment.

PMID- 21170989
TI  - Folic acid and prevention of colorectal adenomas: a combined analysis of
      randomized clinical trials.
AB  - Observational data suggest that lower folate status is associated with an
      increased risk of colorectal neoplasia, implying that folate may be useful as a
      chemopreventive agent. We conducted a combined analysis of three large randomized
      trials of folic acid supplementation for the prevention of metachronous adenomas
      in patients with an adenoma history. Participants included 2,632 men and women
      who had a history of adenomas randomized to either 0.5 or 1.0 mg/day of folic
      acid or placebo and who had a follow-up endoscopy 6 to 42 months after
      randomization [mean = 30.6 (standard deviation = 8.1) months]. We used random
      effects meta-analysis to estimate risk ratios (RRs) and 95% confidence intervals
      (CIs). The RR comparing folic acid versus placebo was 0.98 (95% CI = 0.82-1.17)
      for all adenomas and 1.06 (95% CI = 0.81-1.39) for advanced lesions. Folic acid
      was associated with a nonsignificant decreased risk of any adenoma among subjects
      in the lowest quartile of baseline plasma folate (<= 11 nmol/L) and no effect
      among individuals in the highest quartile (> 29 nmol/L, p for trend = 0.17).
      There was a nonsignificant trend of decreasing risk of any adenoma associated
      with folic acid supplements with increasing alcohol intake. During the early
      follow-up reported here, more deaths occurred in the placebo group than in the
      folic acid group (1.7% vs. 0.5%, p = 0.002). In conclusion, after up to 3.5 years
      of folic acid use, there is no clear decrease or increase in the occurrence of
      new adenomas in patients with a history of adenoma.

PMID- 21170990
TI  - Human ZNF312b oncogene is regulated by Sp1 binding to its promoter region through
      DNA demethylation and histone acetylation in gastric cancer.
AB  - In a previous study, human ZNF312b was identified as a cell proliferation
      associated oncogene via the K-ras/extracellular signal-regulated kinase cascade
      in gastric cancer. However, the mechanism concerning its transcriptional
      activation remains unknown. Here, we show that DNA methylation and histone
      acetylation of the ZNF312b promoter function as a switch for ZNF312b
      transcriptional activation in gastric cancer. The transcription level of ZNF312b
      was increased by treatment with a demethylating agent, 5-aza-2'-deoxycytidine and
      the histone deacetylase inhibitor sodium butyrate, in several human cancer cell
      lines including gastric cancer. Consistent with these results, epigenetic
      analysis, such as pyrosequencing, bisulfate sequencing and methyl-specific
      polymerase chain reaction (MSP), showed that the expression level of ZNF312b is
      highly dependent on the degree of DNA methylation in gastric cancer cell lines.
      In addition, by ChIP assay using anti-acetyl/methyl H3K9 antibodies, histone
      acetylation was shown to mediate the expression of the ZNF312b gene.
      Interestingly, ChIP assay using the Sp1 antibody revealed that the binding of
      transcription factor Sp1 to the ZNF312b promoter for its transcriptional
      activation requires DNA demethylation and histone acetylation. Moreover, a
      knockdown of Sp1 resulted in a decrease in ERK-mediated proliferation via
      downregulation of the ZNF312b gene in gastric cancer cells. Taken together, these
      results suggest that the aberrant expression of ZNF312b promotes gastric
      tumorigenesis through epigenetic modification of its promoter region and provides
      a molecular mechanism for ZNF312b expression to contribute to the progression of
      gastric cancer.

PMID- 21171007
TI  - Chemical synthesis of site-specifically 2'-azido-modified RNA and potential
      applications for bioconjugation and RNA interference.

PMID- 21171012
TI  - Gluconeogenesis in dairy cows: the secret of making sweet milk from sour dough.
AB  - Gluconeogenesis is a crucial process to support glucose homeostasis when
      nutritional supply with glucose is insufficient. Because ingested carbohydrates
      are efficiently fermented to short-chain fatty acids in the rumen, ruminants are
      required to meet the largest part of their glucose demand by de novo genesis
      after weaning. The qualitative difference to nonruminant species is that
      propionate originating from ruminal metabolism is the major substrate for
      gluconeogenesis. Disposal of propionate into gluconeogenesis via propionyl-CoA
      carboxylase, methylmalonyl-CoA mutase, and the cytosolic form of
      phosphoenolpyruvate carboxykinase (PEPCK) has a high metabolic priority and
      continues even if glucose is exogenously supplied. Gluconeogenesis is regulated
      at the transcriptional and several posttranscriptional levels and is under
      hormonal control (primarily insulin, glucagon, and growth hormone).
      Transcriptional regulation is relevant for regulating precursor entry into
      gluconeogenesis (propionate, alanine and other amino acids, lactate, and
      glycerol). Promoters of the bovine pyruvate carboxylase (PC) and PEPCK genes are
      directly controlled by metabolic products. The final steps decisive for glucose
      release (fructose 1,6-bisphosphatase and glucose 6-phosphatase) appear to be
      highly dependent on posttranscriptional regulation according to actual glucose
      status. Glucogenic precursor entry, together with hepatic glycogen dynamics, is
      mostly sufficient to meet the needs for hepatic glucose output except in high
      producing dairy cows during the transition from the dry period to peak lactation.
      Lactating cows adapt to the increased glucose requirement for lactose production
      by mobilization of endogenous glucogenic substrates and increased hepatic PC
      expression. If these adaptations fail, lipid metabolism may be altered leading to
      fatty liver and ketosis. Increasing feed intake and provision of glucogenic
      precursors from the diet are important to ameliorate these disturbances. An
      improved understanding of the complex mechanisms underlying gluconeogenesis may
      further improve our options to enhance the postpartum health status of dairy
      cows.

PMID- 21171015
TI  - Cancer risks for monoallelic MUTYH mutation carriers with a family history of
      colorectal cancer.
AB  - Cancer risks for a person who has inherited a MUTYH mutation from only one parent
      (monoallelic mutation carrier) are uncertain. Using the Colon Cancer Family
      Registry and Newfoundland Familial Colon Cancer Registry, we identified 2,179
      first- and second-degree relatives of 144 incident colorectal cancer (CRC) cases
      who were monoallelic or biallelic mutation carriers ascertained by sampling
      population complete cancer registries in the United States, Canada and Australia.
      Using Cox regression weighted to adjust for sampling on family history, we
      estimated that the country-, age- and sex-specific standardized incidence ratios
      (SIRs) for monoallelic mutation carriers, compared to the general population,
      were: 2.04 (95% confidence interval, CI 1.56-2.70; p < 0.001) for CRC, 3.24
      (95%CI 2.18-4.98; p < 0.001) for gastric cancer, 3.09 (95%CI 1.07-12.25; p =
      0.07) for liver cancer and 2.33 (95%CI 1.18-5.08; p = 0.02) for endometrial
      cancer. Age-specific cumulative risks to age 70 years, estimated using the SIRs
      and US population incidences, were: for CRC, 6% (95%CI 5-8%) for men and 4%
      (95%CI 3-6%) for women; for gastric cancer, 2% (95%CI 1-3%) for men and 0.7%
      (95%CI 0.5-1%) for women; for liver cancer, 1% (95%CI 0.3-3%) for men and 0.3%
      (95%CI 0.1-1%) for women and for endometrial cancer, 4% (95%CI 2-8%). There was
      no evidence of increased risks for cancers of the brain, pancreas, kidney, lung,
      breast or prostate. Monoallelic MUTYH mutation carriers with a family history of
      CRC, such as those identified from screening multiple-case CRC families, are at
      increased risk of colorectal, gastric, endometrial and possibly liver cancers.

PMID- 21171026
TI  - Integrating the science of team training: guidelines for continuing education.
AB  - The provision of high-quality, efficient care results from the coordinated,
      cooperative efforts of multiple technically competent health care providers
      working in concert over time, spanning disciplinary and professional boundaries.
      Accordingly, the role of medical education must include the development of
      providers who are both expert clinicians and expert team members. However, the
      competencies underlying effective teamwork are only just beginning to be
      integrated into medical school curricula and residency programs. Therefore,
      continuing education (CE) is a vital mechanism for practitioners already in the
      field to develop the attitudes, behaviors (skills), and cognitive knowledge
      necessary for highly reliable and effective team performance.The present article
      provides an overview of more than 30 years of evidence regarding team performance
      and team training in order to guide, shape, and build CE activities that focus on
      developing team competencies. Recognizing that even the most comprehensive and
      well-designed team-oriented CE programs will fail unless they are supported by an
      organizational and professional culture that values collaborative behavior, ten
      evidence-based lessons for practice are offered in order to facilitate the use of
      the science of team-training in efforts to foster continuous quality improvement
      and enhance patient safety.

PMID- 21171027
TI  - Presentation of evidence in continuing medical education programs: a mixed
      methods study.
AB  - INTRODUCTION: Clinical trial data can be presented in ways that exaggerate
      treatment effectiveness. Physicians consider therapy more effective, and may be
      more likely to make inappropriate practice changes, when data are presented in
      relative terms such as relative risk reduction rather than in absolute terms such
      as absolute risk reduction and number needed to treat. Our purpose was to
      determine (1) how frequently continuing medical education (CME) speakers present
      research data in relative terms compared to absolute terms; (2) how knowledgeable
      CME speakers and learners are about these terms; and (3) how CME learners want
      these terms presented. METHODS: Analysis of videotapes and PowerPoint slides of
      26 CME presentations, questionnaire survey of CME speakers and learners, and
      focus groups with learners. RESULTS: Speakers presented data more frequently in
      relative than absolute terms, but most frequently in general terms such as
      frequencies, percentages, graphs, and P-values with no data. Of 1367 PowerPoint
      slides, 269 presented research data, and of these, 225 (84%) presented data in
      general terms, 50 (19%) in relative terms and 19 (7%) in absolute terms. CME
      speakers understood relative and absolute terms better than learners.
      Approximately 25-35% of speakers and 45-65% of learners could not correctly
      calculate relative risk reduction, absolute risk reduction, and number needed to
      treat. Learners wished to have these terms presented in CME programs in a
      consistent and easily understood format and requested a brief review of them at
      the beginning of CME programs. DISCUSSION: Presentation of research data in most
      CME programs is inadequate to allow learners to make fully informed therapeutic
      decisions. Speakers and learners need professional development to improve their
      presentation and understanding of research data.

PMID- 21171016
TI  - Bcl-2 promotes malignant progression in a PDGF-B-dependent murine model of
      oligodendroglioma.
AB  - A significant subset of gliomas arises after activation of the proproliferative
      platelet-derived growth factor (PDGF) pathway. The progression of low-grade
      gliomas to more malignant tumors may be due to oncogenic cellular programs
      combining with those suppressing apoptosis. Antiapoptotic genes are overexpressed
      in a variety of cancers, and the antiapoptotic gene, BCL2, is associated with
      treatment resistance and tumor recurrence in gliomas. However, the impact of
      antiapoptotic gene expression to tumor formation and progression is unclear. We
      overexpressed Bcl-2 in a PDGFB-dependent mouse model of oligodendroglioma, a
      common glioma subtype, to assess its effect in vivo. We hypothesized that the
      antiapoptotic effect would complement the proproliferative effect of PDGFB to
      promote tumor formation and progression to anaplastic oligodendroglioma (AO).
      Here, we show that coexpression of PDGFB and Bcl-2 results in a higher overall
      tumor formation rate compared to PDGFB alone. Coexpression of PDGFB and Bcl-2
      promotes progression to AO with prominent foci of necrosis, a feature of high
      grade gliomas. Median tumor latency was shorter in mice injected with PDGFB and
      Bcl-2 compared to those injected with PDGFB alone. Although independent
      expression of Bcl-2 was insufficient to induce tumors, suppression of apoptosis
      (detected by cleaved caspase-3 expression) was more pronounced in AOs induced by
      PDGFB and Bcl-2 compared to those induced by PDGFB alone. Tumor cell
      proliferation (detected by phosphohistone H3 activity) was also more robust in
      high-grade tumors induced by PDGFB and Bcl-2. Our results indicate that
      suppressed apoptosis enhances oligodendroglioma formation and engenders a more
      malignant phenotype.

PMID- 21171028
TI  - A case study in experiential learning: pharmaceutical cold chain management on
      wheels.
AB  - INTRODUCTION: People who handle and regulate temperature-sensitive pharmaceutical
      products require the knowledge and skills to ensure those products maintain
      quality, integrity, safety, and efficacy throughout their shelf life. People best
      acquire such knowledge and skills through "experiential learning" that involves
      working with other learners and experts. METHODS: The World Health Organization
      developed a weeklong experiential learning event for participants so they could
      gain experience in how temperature-sensitive products are handled, stored, and
      distributed throughout the length of the distribution supply chain system. This
      experiential learning method enabled participants to visit, critically observe,
      discuss and report on the various components of the cold chain process. An
      emphasis was placed on team members working together to learn from one another
      and on several global expert mentors who were available to guide the learning,
      share their experiences, and respond to questions. RESULTS: The learning event,
      Pharmaceutical Cold Chain Management on Wheels, has been conducted once each year
      since 2008 in Turkey with participants from the global pharmaceutical industry,
      health care providers, national regulatory authorities, and suppliers/vendors.
      Observations made during the course showed that it was consistent with the
      principles of experiential and social learning theories. Questionnaires and focus
      groups provided evidence of the value of the learning event and ways to improve
      it. DISCUSSION: Reflecting the critical elements derived from experiential and
      social learning theories, five factors contributed to the success of this unique
      experiential learning event. These factors may also have relevance in other
      experiential learning courses and, potentially, for experiential e-learning
      events.

PMID- 21171029
TI  - Assessment of barriers to changing practice as CME outcomes.
AB  - INTRODUCTION: Continuing medical education (CME) is meant to drive and support
      improvements in practice. To achieve this goal, CME activities must move beyond
      simply purveying knowledge, instead helping attendees to contextualize
      information and to develop strategies for implementing new learning. CME
      attendees face different barriers to implementing learning, depending on both
      personal and practice specific contexts. We sought to develop a framework,
      applicable across multiple CME activities, for categorizing barriers that
      learners anticipated encountering after CME activities. METHODS: Building on
      previous work, qualitative research methods were used to develop an enhanced
      framework classifying attendee-perceived barriers to implementing CME learnings
      in practice. Three thousand one hundred thirty (3130) narrative responses on
      attendee-perceived barriers to implementing learnings were collected from 75
      Kaiser Permanente Colorado live CME activities for family medicine, internal
      medicine, pediatric, and OB/GYN clinicians in 2008 and 2009. RESULTS: Our CME
      Learning Transfer Barrier Framework contains 27 discrete barriers in 12 barrier
      categories (including "none"). The barrier framework was applicable across two
      years of live CME activities for different clinician target audiences.
      DISCUSSION: Assessing, characterizing, and summarizing barriers to implementing
      learning during CME activities can provide valuable information to inform
      subsequent CME interventions, and provide feedback to organizational leaders to
      inform performance improvement efforts. The framework may be applicable to other
      CME formats and to CME activities for audiences in different practice settings.

PMID- 21171030
TI  - Defining quality criteria for online continuing medical education modules using
      modified nominal group technique.
AB  - INTRODUCTION: The rapid increase in the use of the Internet for continuing
      education by physicians suggests the need to define quality criteria for
      accredited online modules. METHODS: Continuing medical education (CME) directors
      from Canadian medical schools and academic researchers participated in a
      consensus process, Modified Nominal Group Technique, to develop agreement on the
      most important quality criteria to guide module development. Rankings were
      compared to responses to a survey of a subset of Canadian Medical Association
      (CMA) members. RESULTS: A list of 17 items was developed, of which 10 were deemed
      by experts to be important and 7 were considered secondary. A quality module
      would: be needs-based; presented in a clinical format; utilize evidence-based
      information; permit interaction with content and experts; facilitate and attempt
      to document practice change; be accessible for later review; and include a robust
      course evaluation. There was less agreement among CMA members on criteria
      ranking, with consensus on ranking reached on only 12 of 17 items. In contrast to
      experts, members agreed that the need to assess performance change as a result of
      an educational experience was not important. DISCUSSION: This project identified
      10 quality criteria for accredited online CME modules that representatives of
      Canadian organizations involved in continuing education believe should be taken
      into account when developing learning products. The lack of practitioner support
      for documentation of change in clinical behavior may suggest that they favor
      traditional attendance- or completion-based CME; this finding requires further
      research.

PMID- 21171031
TI  - Perceptions of continuing medical education, professional development, and
      organizational support in the United Arab Emirates.
AB  - INTRODUCTION: This paper investigates the views of health care providers on
      continuous medical education (CME). To our knowledge, this is one of the first
      surveys to examine perspectives of CME in the United Arab Emirates (UAE).
      METHODS: A 6-part questionnaire focused on the following areas of CME: the
      workshop leaders/trainers, the training experience, the relevance of CME
      information provided in the training session, the training approach, the
      convenience of CME sessions, and organizational support. RESULTS: Results from
      147 respondents indicated moderate satisfaction with these 6 CME areas.
      Respondents did not indicate satisfaction with organizational support received.
      Furthermore, participants agreed with the importance of CME to professional
      development. DISCUSSION: In our sample of UAE health care workers, they agree on
      the importance and relevance of CME to the development of their profession, even
      though the majority of health care workers are expatriates. However, several
      issues must be addressed, such as organizational, logistical, and financial
      support to attend CME programs. These issues must be addressed in order to
      sustain the viability of healthcare workers attending CME.

PMID- 21171032
TI  - A targeted e-learning program for surgical trainees to enhance patient safety in
      preventing surgical infection.
AB  - INTRODUCTION: Surgical site infection accounts for 20% of all health care
      associated infections (HCAIs); however, a program incorporating the education of
      surgeons has yet to be established across the specialty. METHODS: An audit of
      surgical practice in infection prevention was carried out in Beaumont Hospital
      from July to November 2009. An educational Web site was developed targeting
      deficiencies highlighted in the audit. Interactive clinical cases were
      constructed using PHP coding, an HTML-embedded language, and then linked to a
      MySQL relational database. PowerPoint tutorials were produced as online Flash
      audiovisual movies. An online repository of streaming videos demonstrating best
      practice was made available, and weekly podcasts were made available on the
      iTunes(c) store for free download. Usage of the e-learning program was assessed
      quantitatively over 6 weeks in May and June 2010 using the commercial company
      Hitslink. RESULTS: During the 5-month audit, deficiencies in practice were
      highlighted, including the timing of surgical prophylaxis (33% noncompliance) and
      intravascular catheter care in surgical patients (38% noncompliance regarding
      necessity). Over the 6-week assessment of the educational material, the
      SurgInfection.com Web pages were accessed more than 8000 times; 77.9% of the
      visitors were from Ireland. The most commonly accessed modality was the
      repository with interactive clinical cases, accounting for 3463 (43%) of the Web
      site visits. The average user spent 57 minutes per visit, with 30% of them
      visiting the Web site multiple times. DISCUSSION: Interactive virtual cases
      mirroring real-life clinical scenarios are likely to be successful as an e
      learning modality. User-friendly interfaces and 24-hour accessibility will
      increases uptake by surgical trainees.

PMID- 21171033
TI  - Indian Supercourse in Epidemiology.

PMID- 21171044
TI  - Simulation of cellular biochemical system kinetics.
AB  - The goal of realistically and reliably simulating the biochemical processes
      underlying cellular function is achievable through a systematic approach that
      makes use of the broadest possible amount of in vitro and in vivo data, and is
      consistent with all applicable physical chemical theories. Progress will be
      facilitated by establishing: (1) a concrete self-consistent theoretical
      foundation for systems simulation; (2) extensive and accurate databases of
      thermodynamic properties of biochemical reactions; (3) parameterized and
      validated models of enzyme and transporter catalytic mechanisms that are
      consistent with physical chemical theoretical foundation; and (4) software tools
      for integrating all these concepts, data, and models into a cohesive
      representation of cellular biochemical systems. Ongoing initiatives are laying
      the groundwork for the broad-based community cooperation that will be necessary
      to pursue these elements of a strategic infrastructure for systems simulation on
      a large scale.

PMID- 21171065
TI  - Treatment of hypokalemic periodic paralysis with topiramate.
AB  - Hypokalemic periodic paralysis (hypoPP), the most common form of periodic
      paralysis, is a disorder characterized by attacks of transient muscle weakness
      associated with a drop in serum potassium level.The mainstay of treatment is
      potassium supplementation and drugs that inhibit the enzyme carbonic anhydrase.
      In this report we describe 11-year-old twins with hypoPP who were treated with
      topiramate, an anti-epileptic drug known to have carbonic anhydrase inhibitory
      properties. The patients experienced a decrease in the severity of their attacks
      upon initiation of treatment. Topiramate may warrant further investigation as a
      treatment option in hypoPP.

PMID- 21171078
TI  - Role of the transcription factor T (brachyury) in the pathogenesis of sporadic
      chordoma: a genetic and functional-based study.
AB  - A variety of analyses, including fluorescence in situ hybridization (FISH),
      quantitative PCR (qPCR) and array CGH (aCGH), have been performed on a series of
      chordomas from 181 patients. Twelve of 181 (7%) tumours displayed amplification
      of the T locus and an additional two cases showed focal amplification; 70/181
      (39%) tumours were polysomic for chromosome 6, and 8/181 (4.5%) primary tumours
      showed a minor allelic gain of T as assessed by FISH. No germline alteration of
      the T locus was identified in non-neoplastic tissue from 40 patients. Copy number
      gain of T was seen in a similar percentage of sacrococcygeal, mobile spine and
      base of skull tumours. Knockdown of T in the cell line, U-CH1, which showed
      polysomy of chromosome 6 involving 6q27, resulted in a marked decrease in cell
      proliferation and morphological features consistent with a senescence-like
      phenotype. The U-CH1 cell line was validated as representing chordoma by the
      generation of xenografts, which showed typical chordoma morphology and
      immunohistochemistry in the NOD/SCID/interleukin 2 receptor [IL2r]gammanull mouse
      model. In conclusion, chromosomal aberrations resulting in gain of the T locus
      are common in sporadic chordomas and expression of this gene is critical for
      proliferation of chordoma cells in vitro.

PMID- 21171080
TI  - Pro-inflammatory chemokine-chemokine receptor interactions within the Ewing
      sarcoma microenvironment determine CD8(+) T-lymphocyte infiltration and affect
      tumour progression.
AB  - Ewing sarcoma is an aggressive round cell sarcoma with poor patient prognosis,
      particularly in cases of advanced-stage disease. Dynamic tumor-host immune
      interations within the tumor microenvironment may polarize in situ immune
      responses and shape tumor development and/or progression. To gain insight into
      the nature of tumour-host immune interactions within the Ewing sarcoma
      microenvironment, the presence and spatial distribution of infiltrating CD8(+)
      /CD4(+) T-lymphocytes were evaluated in therapy-naive Ewing sarcoma. Expression
      profiling of 40 different chemokines and several chemokine receptors was
      performed in therapy-naive tumours and cell lines by qPCR, immunohistochemistry,
      and flow cytometry. Considerable inter-tumour variation was observed regarding
      density, type, and distribution of infiltrating T-lymphocytes. Tumour
      infiltrating T-cells contained significantly higher percentages of CD8(+) T
      lymphocytes as compared to stroma-infiltrating cells, suggesting preferential
      migration of this T-cell type into tumour areas. Gene expression levels of
      several type 1-associated, pro-inflammatory chemokines (CXCR3- and CCR5-ligands
      CXCL9, CXCL10, and CCL5) correlated positively with infiltrating (CD8(+) ) T
      lymphocyte numbers expressing corresponding chemokine receptors. Survival
      analyses demonstrated an impact of tumour-infiltrating, and not stroma
      infiltrating, CD8(+) T-lymphocytes on tumour progression. At protein level, both
      tumour and stromal cells expressed the IFNgamma-inducible chemokines CXCL9 and
      CXCL10. CCR5-ligand CCL5 was exclusively expressed by non-tumoural
      stromal/infiltrating cells. Together, our results indicate that an inflammatory
      immune microenvironment with high expression of type 1-associated chemokines may
      be critical for the recruitment of (CD8(+) ) T-lymphocytes expressing
      corresponding chemokine receptors. The observed impact of tumour-infiltrating
      (CD8(+) ) T-lymphocytes is consistent with a role for adaptive anti-tumour
      immunity in the prevention of Ewing sarcoma progression. Recognition of the
      merits and exploitation/induction of an inflammatory microenvironment may improve
      the efficacy of natural immune responses against, and (adoptive)
      immunotherapeutic approaches for, Ewing sarcoma.

PMID- 21171081
TI  - Objective assessment of lymphatic and blood vascular invasion in lymph node
      negative breast carcinoma: findings from a large case series with long-term
      follow-up.
AB  - In a previous study on a small series of breast cancers, we developed objective
      methods for the assessment of vascular invasion (VI), using immunohistochemical
      staining. We found that VI was predominantly lymphovascular invasion (LVI), with
      minimal contribution of blood vascular invasion (BVI). The aims of the current
      study were: (a) to assess the frequency, extent and prognostic role of LVI and
      BVI in a large, well-characterized series of LN-negative breast cancers; and (b)
      to assess the ability of VI to stratify early breast cancer into different
      prognostic groups. Paraffin-embedded sections from 1005 lymph-node (LN)-negative
      primary invasive breast cancers were stained for CD34, CD31 and podoplanin/D240
      to detect BVI and LVI. VI lesions were assessed and the results were correlated
      with clinicopathological criteria and survival. VI was detected in 218 (22%);
      211/218 (97%) were LVI, while BVI was detected in 7/218 (3%). The frequency of
      LVIs/section ranged from 1 to 79, with no significant difference between the
      frequency of LVI and outcome. The presence of LVI was significantly associated
      with adverse disease-free interval (DFI) and poor overall survival (OS) in both
      univariate and multivariate analyses. The results from the study indicated that
      VI in early stage breast cancer is predominantly LVI and that its objective
      assessment is a powerful independent prognostic factor. Efforts to detect early
      metastatic activity, such as diligent pathological examination of sentinel LN
      biopsies would be complimented by the objective evaluation of VI status of the
      primary tumour. VI status should be included routinely in breast cancer staging
      systems.

PMID- 21171079
TI  - The role of epidermal growth factor receptor in chordoma pathogenesis: a
      potential therapeutic target.
AB  - Chordoma, the molecular hallmark of which is T (brachyury), is a rare malignant
      bone tumour with a high risk of local recurrence and a tumour from which
      metastatic disease is a common late event. Currently, there is no effective drug
      therapy for treating chordomas, although there is evidence that some patients
      respond to the empirical use of epidermal growth factor receptor (EGFR)
      antagonists. The aim of this study was to determine the role of EGFR in the
      pathogenesis of chordoma. Paraffin-embedded material from 173 chordomas from 160
      patients [sacro-coccygeal (n = 94), skull-based (n = 50), and mobile spine (n =
      16)] was analysed by immunohistochemistry and revealed total EGFR expression in
      69% of cases analysed. Of 147 informative chordomas analysed by FISH, 38%
      revealed high-level EGFR polysomy, 4% high-level polysomy with focal
      amplification, 18% low-level polysomy, and 39% disomy. Phospho-receptor tyrosine
      kinase array membranes showed EGFR activation in the chordoma cell line U-CH1 and
      all of the three chordomas analysed. Direct sequencing of EGFR (exons 18-21),
      KRAS, NRAS, HRAS (exons 2, 3), and BRAF (exons 11, 15) using DNA from 62
      chordomas failed to reveal mutations. PTEN expression was absent by
      immunohistochemistry in 19 of 147 (13%) analysed chordomas, only one of which
      revealed high-level polysomy of EGFR. The EGFR inhibitor tyrphostin (AG 1478)
      markedly inhibited proliferation of the chordoma cell line U-CH1 in vitro and
      diminished EGFR phosphorylation in a dose-dependant manner, a finding supported
      by inhibition of phosphorylated Erk1/2. p-Akt was suppressed to a much lesser
      degree in these experiments. There was no reduction of T as assessed by western
      blotting. These data implicate aberrant EGFR signalling in the pathogenesis of
      chordoma. This study provides a strategy for patient stratification for treatment
      with EGFR antagonists.

PMID- 21171082
TI  - Betel-derived alkaloid up-regulates keratinocyte alphavbeta6 integrin expression
      and promotes oral submucous fibrosis.
AB  - Oral submucous fibrosis (OSF) is a premalignant, fibrosing disorder of the mouth,
      pharynx, and oesophagus, with a malignant transformation rate of 7-13%. OSF is
      strongly associated with areca (betel) nut chewing and worldwide, over 5 million
      people are affected. As alphavbeta6 integrin is capable of promoting both tissue
      fibrosis and carcinoma invasion, we examined its expression in fibroepithelial
      hyperplasia and OSF. alphavbeta6 was markedly up-regulated in OSF, with high
      expression detected in 22 of 41 cases (p < 0.001). We investigated the functional
      role of alphavbeta6 using oral keratinocyte-derived cells genetically modified to
      express high alphavbeta6 (VB6), and also NTERT-immortalized oral keratinocytes,
      which express low alphavbeta6 (OKF6/TERT-1). VB6 cells showed significant
      alphavbeta6-dependent activation of TGF-beta1, which induced transdifferentiation
      of oral fibroblasts into myofibroblasts and resulted in up-regulation of genes
      associated with tissue fibrosis. These experimental in vitro findings were
      confirmed using human clinical samples, where we showed that the stroma of OSF
      contained myofibroblasts and that TGF-beta1-dependent Smad signalling was
      detectable both in keratinocytes and in myofibroblasts. We also found that
      arecoline, the major alkaloid of areca nuts, up-regulated keratinocyte
      alphavbeta6 expression. This was modulated through the M(4) muscarinic
      acetylcholine receptor and was suppressed by the M(4) antagonist, tropicamide.
      Arecoline-dependent alphavbeta6 up-regulation promoted keratinocyte migration and
      induced invasion, raising the possibility that this mechanism may support
      malignant transformation. Over 80% of OSF-related oral cancers examined had
      moderate/high alphavbeta6 expression. These data suggest that the pathogenesis of
      OSF may be epithelial-driven and involve arecoline-dependent up-regulation of
      alphavbeta6 integrin.

PMID- 21171083
TI  - TNF-related apoptosis-inducing ligand cooperates with NSAIDs via activated Wnt
      signalling in (pre)malignant colon cells.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) receptor agonistic agents and non
      steroidal anti-inflammatory drugs (NSAIDs) are interesting agents for the
      chemoprevention and treatment of colorectal cancer. We investigated whether
      NSAIDs sensitize colon cancer and adenoma cell lines and ex vivo cultured human
      adenomas to recombinant human (rh)TRAIL. Involvement of the crucial Wnt
      signalling pathway in the sensitization of colon cancer cells was examined. Five
      colon cancer and two adenoma cell lines, human ex vivo adenomas and normal
      colonic epithelium were treated with aspirin or sulindac combined with rhTRAIL.
      Apoptosis levels, expression of intracellular proteins and TRAIL receptor
      membrane expression were assessed. Ls174T cells stably transfected with an
      inducible dominant negative TCF-4 (dnTCF-4) construct served to analyse the role
      of Wnt pathway activation. Both rhTRAIL-sensitive and -resistant colon cancer
      cell lines were strongly sensitized to rhTRAIL by aspirin (maximum enhancement
      ratio, 7.1). Remarkably, in adenoma cell lines sulindac enhanced rhTRAIL-induced
      apoptosis most effectively (maximum enhancement ratio, 2.5). Although membrane
      TRAIL receptor expression was not affected by NSAIDs, caspase-8 activation was
      enhanced by combinational treatment. Several proteins from different biological
      pathways were affected by NSAIDs, indicating complex mechanisms of sensitization.
      Elimination of TCF-4 completely blocked the sensitizing effect in colon cancer
      cells. In ex vivo adenomas the combination of sulindac and rhTRAIL increased
      apoptosis from 18.4% (sulindac) and 17.8% (rhTRAIL) to 28.0% (p = 0.003 and p =
      0.005, respectively). It was concluded that NSAID-induced sensitization to
      rhTRAIL requires TCF-4 activity. Thus, the combination of TRAIL-receptor
      agonistic agents and NSAIDs is a potentially attractive treatment option for
      (pre)malignant tumours with constitutively active Wnt signalling, such as
      colorectal tumours.

PMID- 21171084
TI  - Mutant K-ras promotes carcinogen-induced murine colorectal tumourigenesis, but
      does not alter tumour chromosome stability.
AB  - K-ras (KRAS) mutations are observed in around 40% of human colorectal adenomas
      and carcinomas. Previously, we developed and characterized a strain of transgenic
      mice with inducible intestinal epithelial expression of K-ras{Val12} via a
      Cre/LoxP system. To evaluate the influence of mutant K-ras on carcinogen-induced
      colorectal tumourigenesis, we induced neoplastic alterations in the large
      intestines of wild-type and K-ras{Val12} mice using the colon-selective
      carcinogen 1,2-dimethylhydrazine (DMH), which has been widely used to induce
      colorectal tumours that are histopathologically similar to those observed in
      humans. K-ras{Val12} expression significantly promoted DMH-induced colorectal
      tumourigenesis: the average lifespan of the mice decreased from 38.52 +/- 1.97
      weeks for 40 control mice to 32.42 +/- 2.17 weeks for 26 K-ras{Val12} mice (mean
      +/- SEM, p < 0.05) and the abundance of large intestinal tumours increased from
      2.27 +/- 0.15 per control mouse to 3.85 +/- 0.20 in K-ras{Val12} mice (mean +/-
      SEM, p < 0.01). Adenomas from DMH-treated K-ras{Val12} mice showed significantly
      higher proportions of Ki-67-positive proliferating cells (10.9 +/- 0.69%)
      compared with those from DMH-treated wild-type mice (7.77 +/- 0.47%) (mean +/-
      SEM, p < 0.01) and a mild increase in apoptotic nuclei staining for cleaved
      caspase-3 (1.94 +/- 0.21% compared with 1.15 +/- 0.14%, mean +/- SEM, p < 0.01).
      In the adenomas from DMH-treated K-ras{Val12} mice, K-ras{Val12} transgene
      recombination and expression were confirmed, with immunohistochemical evidence of
      strong Erk/MapK and mild PI3K/Akt pathway activation compared with adenomas from
      DMH-treated wild-type mice. Microarray hybridization and clustering analysis
      demonstrated different expression profiles in adenomas from DMH-treated wild-type
      and DMH-treated K-ras{Val12} mice, indicating involvement of different molecular
      mechanisms including Erk/MapK and PI3K/Akt signalling in K-ras{Val12}-expressing
      adenomas. Array-comparative genomic hybridization analysis showed chromosome
      stability in both cohorts, with only a very few tiny alterations observed in one
      adenoma from a DMH-treated K-ras{Val12} mouse. Taken together, these data show
      that mutant K-ras significantly promotes DMH-induced colorectal tumourigenesis,
      resulting in distinct changes in cell signalling and proliferation, but does not
      alter chromosome stability in the tumours.

PMID- 21171086
TI  - Alcoholics show reduced telomere length in the oesophagus.
AB  - Telomeres are repetitive G-rich DNA sequences located at the ends of chromosomes.
      Chromosomal and genomic instability due to telomere dysfunction plays an
      important role in carcinogenesis. To study telomere shortening in the oesophageal
      epithelium of alcoholics, we measured the telomere lengths of basal and parabasal
      cells in comparison with those of non-alcoholics using Q-FISH and our original
      software, Tissue Telo, and also assessed histological inflammation. Telomeres in
      basal cells were significantly shorter in alcoholics than in age-matched normal
      controls. Prominent histological findings of chronic inflammation were not
      evident in either alcoholics or non-alcoholics. Our finding that telomeres in the
      oesophageal epithelium are shorter in alcoholics than in non-alcoholics indicates
      that telomere shortening may be associated with the frequent occurrence of
      squamous cell carcinoma in alcoholics. Further studies to clarify the reason for
      the large annual loss of telomere length with rapid turnover or lower telomerase
      activity in the oesophageal epithelium of alcoholics will be necessary.

PMID- 21171085
TI  - BCL2L10 protein regulates apoptosis/proliferation through differential pathways
      in gastric cancer cells.
AB  - The reason for and consequences of BCL2L10 down-regulation in gastric carcinoma
      are poorly understood. Our aim was to investigate the function of the protein
      BCL2L10 in gastric carcinoma. We investigated BCL2L10 expression using
      quantitative real-time PCR and immunoblotting. The methylation status of the
      BCL2L10 gene promoter was examined by bisulphite sequencing in fresh gastric
      normal and carcinoma tissues. We studied apoptosis and proliferation regulation
      in gastric cancer cell lines using flow cytometry, fluorescence staining, murine
      xenografting and immunoblotting. Pathway inhibitors were applied to confirm the
      major pathways involved in apoptosis or proliferation regulation. We observed
      significant correlations between lower BCL2L10 expression and CpG island
      hypermethylation of the BCL2L10 gene promoter in gastric carcinoma, apoptosis
      induced by over-expressed BCL2L10 through mitochondrial pathways, and
      proliferation accelerated by BCL2L10 siRNA via the PI3K-Akt signalling pathway in
      gastric cancer cell lines. The pro-apoptotic effect of BCL2L10 and growth
      promotion by BCL2L10 siRNA in gastric cancer cells suggest that it may be a
      tumour suppressor.

PMID- 21171087
TI  - Activation of lung macrophage subpopulations in experimental acute pancreatitis.
AB  - Pulmonary macrophages exist in two different anatomical compartments in the lower
      respiratory tract: alveolar macrophages in the alveoli and interstitial
      macrophages in the interstitium. Depending on the micro-environmental
      stimulation, macrophages follow different activation pathways. According to their
      inflammatory response pattern, activated macrophages have been characterized as
      pro-inflammatory (M1), wound-healing (M2a) and regulatory (M2b). Since acute
      pancreatitis occurs in parallel with acute lung injury, the profile of the
      different macrophage subpopulations could be relevant in the progression of the
      disease. The activation of lung alveolar and interstitial macrophages was
      assessed in an experimental model of severe acute pancreatitis induced in rats by
      intraductal infusion of 3.5% sodium taurocholate. Alveolar and interstitial
      macrophages were obtained and the expression of markers of different activations
      was evaluated. Activation of nuclear factors PPARgamma and NF-kappaB, which are
      involved in the acquisition of different phenoytpes, was also measured. Alveolar
      macrophages acquired an early M1 phenotype characterized by the expression of
      inflammatory cytokines and NF-kappaB activation. In contrast, interstitial
      macrophages followed the inhibitory M2b pathway. In these macrophages, PPARgamma
      became activated and the anti-inflammatory cytokine IL-10 was expressed. These
      results suggest that alveolar and interstitial macrophages play different roles
      in acute lung injury associated with acute pancreatitis. Alveolar macrophages
      promote an early inflammatory response, whereas interstitial macrophages help
      resolve inflammation.

PMID- 21171088
TI  - Immunohistochemical expression of conjugating UGT1A-derived isoforms in normal
      and tumoral drug-metabolizing tissues in humans.
AB  - Glucuronidation by UDP-glucuronyltransferase (UGT) enzymes is the prevailing
      conjugative pathway for the metabolism of both xenobiotics and endogenous
      compounds. Alterations in this pathway, such as those generated by common genetic
      polymorphisms, have been shown to significantly impact on the health of
      individuals, influencing cancer susceptibility, responsiveness to drugs and drug
      induced toxicity. Alternative usage of terminal exons leads to UGT1A-derived
      splice variants, namely the classical and enzymatically active isoforms 1 (i1)
      and the novel enzymatically inactive isoforms 2 (i2). In vitro functional data
      from heterologous expression and RNA interference experiments indicate that these
      i2 isoforms act as negative modulators of glucuronidation, likely by forming
      inactive complexes with active isoform 1. We used specific antibodies against
      either active i1 or inactive i2 proteins to examine their distribution in major
      drug-metabolizing tissues. Data revealed that UGT1A_i1 and inactive UGT1A_i2 are
      co-produced in the same tissue structures, including liver, kidney, stomach,
      intestine and colon. Examination of the cellular distribution and semi
      quantitative level of expression of UGT1As revealed heterogeneous expression of
      i1 and i2 proteins, with increased expression of i2 in liver tumours and
      decreased levels of i1 and i2 in colon cancer specimens, compared to normal
      tissues. These differences in expression may be relevant to human colon and liver
      cancer tumorigenesis. Our data clearly demonstrate the similar immunolocalization
      of active and inactive UGT1A isoforms in most UGT1A-expressing cell types of
      major tissues involved in drug metabolism. These expression patterns are
      consistent with a dominant-negative function for the i2 encoded by the UGT1A
      gene.

PMID- 21171089
TI  - IKBKE is over-expressed in glioma and contributes to resistance of glioma cells
      to apoptosis via activating NF-kappaB.
AB  - IkappaB kinase-epsilon (IKBKE), a member of the IkappaB kinase (IKK) family, has
      been identified as an oncogenic protein and found to be up-regulated in breast
      cancer, ovarian cancer and prostate cancer. Nonetheless, the expression status
      and functional significance of IKBKE in human glioma remain unexplored. For the
      first time, we have demonstrated that mRNA and protein levels of IKBKE were
      robustly up-regulated in glioma cell lines and human primary glioma tissues.
      Immunohistochemistry analysis revealed that 53.5% (38/71) paraffin-embedded
      archived glioma specimens exhibited high levels of IKBKE expression.
      Intriguingly, there was no significant difference in IKBKE expression among
      different grades of glioma. To understand the biological function of IKBKE in the
      development and progression of human glioma, glioma cells lines ectopically over
      expressing IKBKE were established and tested for their responsiveness to
      apoptotic inducers. Our data showed that IKBKE over-expression inhibited cell
      apoptosis induced by UV irradiation or adriamycin and, in contrast, shRNAi
      mediated suppression of IKBKE increased the sensitivity of glioma cells to the
      apoptotic inducers. Importantly, we found that up-regulated IKBKE could induce
      the expression of Bcl-2 through activating NF-kappaB signalling, and that,
      specifically, we identified IkappaB as a critical component for this signalling
      cascade. The current study suggests that up-regulation of IKBKE may represent an
      important molecular hallmark that is biologically and clinically relevant to the
      development and progression, as well as the chemo- and radio-resistance, of the
      disease.

PMID- 21171091
TI  - Some changes in the journal.

PMID- 21171092
TI  - Automated hand-held nerve conduction devices: raw data, raw interpretations.

PMID- 21171093
TI  - Motor neuron disease due to neuropathy target esterase gene mutation: clinical
      features of the index families.
AB  - Recently, we reported that mutations in the neuropathy target esterase (NTE) gene
      cause autosomal recessive motor neuron disease (NTE-MND). We describe clinical,
      neurophysiologic, and neuroimaging features of affected subjects in the index
      families. NTE-MND subjects exhibited progressive lower extremity spastic weakness
      that began in childhood and was later associated with atrophy of distal leg and
      intrinsic hand muscles. NTE-MND resembles Troyer syndrome, except that short
      stature, cognitive impairment, and dysmorphic features, which often accompany
      Troyer syndrome, are not features of NTE-MND. Early onset, symmetry, and slow
      progression distinguish NTE-MND from typical amyotrophic lateral sclerosis. NTE
      is implicated in organophosphorus compound-induced delayed neurotoxicity (OPIDN).
      NTE-MND patients have upper and lower motor neuron deficits that are similar to
      OPIDN. Motor neuron degeneration in subjects with NTE mutations supports the role
      of NTE and its biochemical cascade in the molecular pathogenesis of OPIDN and
      possibly other degenerative neurologic disorders.

PMID- 21171094
TI  - Insights into genotype-phenotype correlations in spinal muscular atrophy: a
      retrospective study of 103 patients.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive disorder associated with
      homozygous deletion of the survival motor neuron 1 gene (SMN1). Its centromeric
      copy gene, SMN2, is the major modifying factor. However, the genotype-phenotype
      correlation is incomplete and is therefore not useful in clinical practice. We
      studied a cohort of 103 patients in order to refine this correlation. In addition
      to standard disease severity data, we collected three additional criteria: age at
      death; brainstem involvement; and loss of ambulation. Gene dosage analysis was
      conducted by multiplex ligation-dependent probe amplification (MLPA). SMN2
      copynumber was highly correlated with survival duration in SMA type I and
      ambulation conservation or loss in type III. Among SMA severity groups, it was
      not significantly different in cases with brainstem involvement. Although the
      SMN2 copynumber could provide prognostic indications, clinical discrepancies
      still exist among patients, suggesting the existence of unidentified modifying
      factors.

PMID- 21171095
TI  - Activity-dependent conduction block in multifocal motor neuropathy.
AB  - Previous studies suggested that activity-dependent conduction block (CB)
      contributes to weakness in multifocal motor neuropathy (MMN). Obtaining more
      robust evidence for activity-dependent CB is important because it may be a novel
      target for treatment strategies. We performed nerve conduction studies in 22
      nerve segments of 19 MMN patients, before and immediately after 60 seconds of
      maximal voluntary contraction (MVC) of the relevant muscle. We employed
      supramaximal electrical stimulation, excluded nerves with marked axonal loss, and
      adopted criteria for activity-dependent CB. Per segment, the segmental area ratio
      [area proximal compound muscle action potential (CMAP)/area distal CMAP] was
      calculated and, per nerve, total area ratio (area CMAP at Erb's point/area distal
      CMAP) was obtained. MVC induced no changes in mean area ratios and induced no
      activity-dependent CB. In segments with CB before MVC, the MVC induced increased
      duration prolongation. In MMN, MVC induced temporal dispersion but no activity
      dependent CB.

PMID- 21171096
TI  - Exercise training enhances the skeletal muscle response to radiation-induced
      oxidative stress.
AB  - Overproduction of reactive oxygen species (ROS) can damage cellular
      macromolecules and lead to cellular dysfunction or death. Exercise training
      induces beneficial adaptations in skeletal muscle that may reduce cellular damage
      from exposure to ROS. To determine the response of exercise-conditioned muscle to
      acute increases in ROS, four groups of mice were used: non-trained (NT, n = 12);
      NT + high-dose radiation (HDR, n = 3); exercise-trained (EX, n = 13, 3 days/week
      for 10 weeks, 10 m/min to 18 m/min); and EX + HDR (n = 3/group). Quadriceps
      muscle was harvested 3-5 days following the last exercise bout in the training
      program for measurement of antioxidant enzyme and metabolic enzyme activity.
      Total superoxide dismutase (41%), and manganese sodium oxide dismutase (51%)
      activities were significantly increased in radiation-challenged EX mice as
      compared with unchallenged EX mice (all P <= 0.05). No such increase was observed
      in NT mice. Citrate synthase (42%) and cytochrome c oxidase (38%) activities were
      both elevated in radiation-challenged EX mice as compared with unchallenged EX
      mice (both P < 0.05), and no such increase was observed in NT. We demonstrate
      that preconditioning skeletal muscle with EX enhances the response of antioxidant
      and mitochondrial enzymes to radiation.

PMID- 21171097
TI  - Altered mRNA expression after long-term soleus electrical stimulation training in
      humans with paralysis.
AB  - In humans, spinal cord injury (SCI) induces deleterious changes in skeletal
      muscle that may be prevented or reversed by electrical stimulation muscle
      training. The molecular mechanisms underlying muscle stimulation training remain
      unknown. We studied two unique SCI subjects whose right soleus received >6 years
      of training (30 minutes/day, 5 days/week). Training preserved torque, fatigue
      index, contractile speed, and cross-sectional area in the trained leg, but not
      the untrained leg. Training decreased 10 mRNAs required for fast-twitch
      contractions and mRNA that encodes for myostatin, an autocrine/paracrine hormone
      that inhibits muscle growth. Conversely, training increased 69 mRNAs that mediate
      the slow-twitch, oxidative phenotype, including PGC-1alpha, a transcriptional
      coactivator that inhibits muscle atrophy. When we discontinued right soleus
      training, training-induced effects diminished slowly, with some persisting for >6
      months. Training of paralyzed muscle induces localized and long-lasting changes
      in skeletal muscle mRNA expression that improve muscle mass and function.

PMID- 21171098
TI  - Evaluation of skeletal muscle during calf exercise by 31-phosphorus magnetic
      resonance spectroscopy in patients on statin medications.
AB  - Muscle pain is a common side effect of statin medications, but the cause is
      poorly understood. We characterized phosphocreatine (PCr) exercise recovery
      kinetics in 10 patients with hypercholesterolemia before and after a 4-week
      regimen of statin therapy using 31-phosphorus magnetic resonance spectroscopy
      ((31) P-MRS). (31) P spectra were obtained before, during, and after exercise on
      a calf flexion pedal ergometer. Creatine kinase (CK) serum levels were drawn
      before and after statin therapy. The mean metabolic recovery time constant in
      subjects increased from 28.1 s (SE = 6.5 s) to 55.4 s (SE = 7.4 s) after statin
      therapy. The unweighted mean of the pre/post-recovery time difference was -27.3 s
      (SE = 12.4 s; P = 0.02). Pre- and post-therapy CK levels were not significantly
      different (P = 0.50). Metabolic recovery time in the calf is prolonged in
      patients after statin use. This suggests that statins impair mitochondrial
      oxidative function, and (31) P MRS is a potential study model for statin
      associated myopathy.

PMID- 21171099
TI  - Carbamylated erythropoietin does not alleviate signs of dystrophy in mdx mice.
AB  - Erythropoietin promotes myoblast proliferation and inhibits fibrosis and thus it
      could impede the pathogenesis of muscle degenerative diseases. However, its
      stimulation of erythropoiesis limits its use as a therapeutic agent. An
      erythropoietin analog, carbamylated erythropoietin (C-EPO), retains these
      protective actions, yet it does not interact with the erythropoietin receptor. To
      determine whether treatment with C-EPO alleviates the signs of muscular dystrophy
      in an animal model of Duchenne muscular dystrophy, we treated mdx mice with
      intraperitoneal injections of 50 MUg/kg and 100 MUg/kg C-EPO for 4 and 12 weeks,
      and we monitored weight, serum creatine kinase levels, and changes in muscle
      histology. Moderate histological improvement was observed at 4 weeks, which did
      not translate into a significantly decreased level of serum creatine kinase. At
      the doses tested, C-EPO is not an effective therapeutic for the treatment of a
      mouse model of Duchenne muscular dystrophy.

PMID- 21171100
TI  - Doxorubicin causes diaphragm weakness in murine models of cancer chemotherapy.
AB  - Doxorubicin is a chemotherapeutic agent prescribed for a variety of tumors. While
      undergoing treatment, patients exhibit frequent symptoms that suggest respiratory
      muscle weakness. Cancer patients can receive doxorubicin chemotherapy through
      either intravenous (IV) or intraperitoneal (IP) injections. We hypothesized that
      respiratory muscle function would be depressed in a murine model of chemotherapy.
      We tested this hypothesis by treating C57BL/6 mice with a clinical dose of
      doxorubicin (20 mg/kg) via IV or IP injection. Three days later we measured
      contractile properties of muscle fiber bundles isolated from the diaphragm.
      Doxorubicin consistently depressed diaphragm force with both methods of
      administration (P < 0.01). Doxorubicin IP exaggerated the depression in diaphragm
      force and stimulated tissue inflammation and muscle fiber injury. These results
      suggest that clinically relevant doses of doxorubicin cause respiratory muscle
      weakness and that the loss of function depends, in part, on the route of
      administration.

PMID- 21171101
TI  - Interactive effects of corticosteroid and mechanical ventilation on diaphragm
      muscle function.
AB  - Information on the interactive effects of methylprednisolone, controlled
      mechanical ventilation (CMV), and assisted mechanical ventilation (AMV) on
      diaphragm function is sparse. Sedated rabbits received 2 days of CMV, AMV, and
      spontaneous breathing (SB), with either methylprednisolone (MP; 60 mg/kg/day
      intravenously) or saline. There was also a control group. In vitro diaphragm
      force, myofibril ultrastructure, alphaII-spectrin proteins, insulin-like growth
      factor-1 (IGF-1), and muscle atrophy F-box (MAF-box) mRNA were measured. Maximal
      tetanic tension (P(o)) decreased significantly with CMV. Combined MP plus CMV did
      not decrease P(o) further. With AMV, P(o) was similar to SB and controls.
      Combined MP plus AMV or MP plus SB decreased P(o) substantially. Combined MP plus
      CMV, MP plus AMV, or MP plus SB induced myofibrillar disruption that correlated
      with the reduced P(o). alphaII-spectrin increased, IGF-1 decreased, and MAF-box
      mRNA increased in both the CMV group and MP plus CMV group. Short-term, high-dose
      MP had no additive effects on CMV-induced diaphragm dysfunction. Combined MP plus
      AMV impaired diaphragm function, but AMV alone did not. We found that acute, high
      dose MP produces diaphragm dysfunction depending on the mode of mechanical
      ventilation.

PMID- 21171103
TI  - Late onset oculopharyngeal muscular dystrophy with prominent neurogenic features
      and short GCG trinucleotide expansion.

PMID- 21171102
TI  - Costimulation blockade inhibits the indirect pathway of allorecognition in nerve
      allograft rejection.
AB  - Nerve allografts provide a temporary scaffold for host nerve regeneration. The
      need for systemic immunosuppression limits clinical application. Characterization
      of the immunological mechanisms that induce immune hyporesponsiveness may provide
      a basis for optimizing immunomodulating regimens. We utilized wild-type and MHC
      class II-deficient mice, as both recipients and donors. Host treatment consisted
      of triple costimulatory blockade. Quantitative assessment was made at 3 weeks
      using nerve histomorphometry, and muscle testing was performed on a subset of
      animals at 7 weeks. Nerve allograft rejection occurred as long as either the
      direct or indirect pathways were functional. Indirect antigen presentation
      appeared to be more important. Nerve allograft rejection occurs in the absence of
      a normal direct or indirect immune response but may be more dependent on indirect
      allorecognition. The indirect pathway is required to induce costimulatory
      blockade immune hyporesponsiveness.

PMID- 21171106
TI  - Muscle strength and fatigue in patients with generalized myasthenia gravis.

PMID- 21171111
TI  - Capacitively coupled contactless conductivity detection for microseparation
      techniques - recent developments.
AB  - An overview of the developments of capacitively coupled contactless conductivity
      detection in CE and related techniques over approximately the last 2 years is
      given. The method has seen strong growth, and diverse new applications are being
      reported. Besides more advanced techniques on conventional capillaries, these
      include further developments of detection on lab-on-chip devices as well as in
      miniaturized chromatographic systems and some methods not involving separations.
      An increasing number of reports are based on the now readily available commercial
      detectors, but, while few publications on fundamental studies have appeared
      recently, interesting new approaches on creating low cost devices have also
      appeared.

PMID- 21171109
TI  - Recent advances in the MS analysis of glycoproteins: Theoretical considerations.
AB  - Protein glycosylation is involved in a broad range of biological processes that
      regulate protein function and control cell fate. As aberrant glycosylation has
      been found to be implicated in numerous diseases, the study and large-scale
      characterization of protein glycosylation is of great interest not only to the
      biological and biomedical research community, but also to the pharmaceutical and
      biotechnology industry. Due to the complex chemical structure and differing
      chemical properties of the protein/peptide and glycan moieties, the analysis and
      structural characterization of glycoproteins has been proven to be a difficult
      task. Large-scale endeavors have been further limited by the dynamic outcome of
      the glycosylation process itself, and, occasionally, by the low abundance of
      glycoproteins in biological samples. Recent advances in MS instrumentation and
      progress in miniaturized technologies for sample handling, enrichment and
      separation, have resulted in robust and compelling analysis strategies that
      effectively address the challenges of the glycoproteome. This review summarizes
      the key steps that are involved in the development of efficient glycoproteomic
      analysis methods, and the latest innovations that led to successful strategies
      for the characterization of glycoproteins and their corresponding glycans. As a
      follow-up to this work, we review innovative capillary and microfluidic-MS
      workflows for the identification, sequencing and characterization of
      glycoconjugates.

PMID- 21171112
TI  - Recent advances in CE-MS: Synergy of wet chemistry and instrumentation
      innovations.
AB  - CE with MS detection is a hyphenated technique which greatly improves the ability
      of CE to deal with real samples, especially with those coming from biology and
      medicine, where the target analytes are present as trace amounts in very complex
      matrices. CE-MS is now almost a routine technique performed on commercially
      available instruments. It faces currently a tremendous development of the
      technique itself as well as of its wide application area. Great interest in CE-MS
      is reflected in the scientific literature by many original research articles and
      also by numerous reviews. The review presented here has a general scope and
      belongs to a series of regularly published reviews on the topic. It covers the
      literature from the last 2 years, since January 2008 till June 2010. It brings a
      critical selection of related literature sorted into groups reflecting the main
      topics of actual scientific interest: (i) innovations in CE-ESI-MS, (ii) use of
      alternative interfaces, and (iii) ways to enhance sensitivity. Special attention
      is paid to novel electrolyte systems amenable to CE-MS including nonvolatile
      BGEs, to advanced CE separation principles such as MEKC, MEEKC, chiral CE, and to
      the use of preconcentration techniques.

PMID- 21171113
TI  - CE-MS for metabolomics: Developments and applications in the period 2008-2010.
AB  - This review provides an update of the state-of-the-art of CE-MS for metabolomic
      purposes, covering the scientific literature from July 2008 to June 2010. This
      review describes the different analytical aspects with respect to non-targeted
      and targeted metabolomics and the new technological developments used in CE-MS
      for metabolomics. The applicability of CE-MS in metabolomics research is
      illustrated by examples of the analysis of biomedical and clinical samples, and
      for bacterial and plant extracts. The relevant papers on CE-MS for metabolomics
      are comprehensively summarized in a table, including, e.g. information on sample
      type and pretreatment, and MS detection mode. Future considerations such as
      challenges for large-scale and (quantitative) clinical metabolomics studies and
      the use of sheathless interfacing and different ionization techniques are
      discussed.

PMID- 21171110
TI  - Recent advances in the MS analysis of glycoproteins: Capillary and microfluidic
      workflows.
AB  - Recent developments in bioanalytical instrumentation, MS detection, and
      computational data analysis approaches have provided researchers with
      capabilities for interrogating the complex cellular glycoproteome, to help gain a
      better insight into the cellular and physiological processes that are associated
      with a disease and to facilitate the efforts centered on identifying disease
      specific biomarkers. This review describes the progress achieved in the
      characterization of protein glycosylation by using advanced capillary and
      microfluidic MS technologies. The major steps involved in large-scale
      glycoproteomic analysis approaches are discussed, with special emphasis given to
      workflows that have evolved around complex MS detection functions. In addition,
      quantitative analysis strategies are assessed, and the bioinformatics aspects of
      glycoproteomic data processing are summarized. The developments in commercial and
      custom fabricated microfluidic front-end platforms to ESI- and MALDI-MS
      instrumentation, for addressing major challenges in carbohydrate analysis such as
      sensitivity, throughput, and ability to perform structural characterization, are
      further evaluated and illustrated with relevant examples.

PMID- 21171114
TI  - Capillary electrophoresis-mass spectrometry for the analysis of intact proteins
      2007-2010.
AB  - CE coupled to MS has proven to be a powerful analytical tool for the
      characterization of intact proteins, as it combines the high separation
      efficiency of CE with the selectivity of MS. This review provides an overview of
      the development and application of CE-MS methods within the field of intact
      protein analysis as published between January 2007 and June 2010. Ongoing
      technological developments with respect to CE-MS interfacing, capillary coatings
      for CE-MS, coupling of CIEF with MS and chip-based CE-MS are treated.
      Furthermore, CE-MS of intact proteins involving ESI, MALDI and ICP ionization is
      outlined and overviews of the use of the various CE-MS methods are provided by
      tables. Representative examples illustrate the applicability of CE-MS for the
      characterization of proteins, including glycoproteins, biopharmaceuticals,
      protein-ligand complexes, biomarkers and dietary proteins. It is concluded that
      CE-MS is a valuable technique with high potential for intact protein analysis,
      providing useful information on protein identity and purity, including
      modifications and degradation products.

PMID- 21171115
TI  - Recent progress in analytical capillary isotachophoresis.
AB  - Capillary ITP is currently used as one of the most important tools for
      preseparation and preconcentration of trace analytes in complex or diluted
      samples. This contribution is a continuation of a series of regularly published
      reviews on the topic and covers the last 2 years. It brings a survey of related
      literature organized into following sections: theory and methodology,
      instrumentation and techniques, and applications.

PMID- 21171116
TI  - Trends in nonpolar polymer-based monolithic columns for reversed-phase capillary
      electrochromatography.
AB  - This review article is concerned with describing the various strategies that have
      been introduced for the preparation of nonpolar polymer-based monolithic columns
      for RP-CEC. First, the various traditional ways of generating the EOF that
      involved the introduction of fixed charges on the surface of the monoliths are
      reviewed. This is followed by a description of the development of neutral
      monoliths as the most promising monoliths for the separation of a wide range of
      neutral and charged species at a relatively moderate to strong EOF in the absence
      of electrostatic attraction or repulsion.

PMID- 21171117
TI  - Preparation and application of organic-silica hybrid monolithic capillary
      columns.
AB  - Organic-silica hybrid monolithic columns have drawn more and more attention due
      to the ease of preparation and good mechanical stability in recent years. Many
      synthetic approaches have been developed and a variety of hybrid monolithic
      capillary columns have been prepared. The sol-gel process is well recognized in
      the fabrication of hybrid monolithic columns, which can be mainly classified as
      one-step, acid/base two-step procedures. The new approaches such as the "one-pot"
      and nano-scaled inorganic-organic hybrid reagent of polyhedral oligomeric
      silsesquioxane used as a cross-linker have also emerged for the preparation of
      hybrid monolithic columns. The applications of the organic-silica hybrid
      monolithic capillary columns for capillary electrochromatography, micro high
      performance liquid chromatography, solid-phase micro-extraction and enzymatic
      reactor etc. are included in this review.

PMID- 21171118
TI  - Contemporary sample stacking in analytical electrophoresis.
AB  - Sample stacking is of vital importance for analytical CE since it may bring the
      required sensitivity of analyses. A lot of new relevant papers are published
      every year and regular surveys seem to be very helpful for experts and
      practitioners. The contribution presented here is a continuation of a series of
      regularly published reviews on the topic and covers the last two years. It brings
      a survey of related literature organized, in accord with the main principle used
      in the procedure published, in the following mainstream sections: Kohlrausch
      adjustment of concentrations, pH step, micellar systems and combined techniques.
      Each part covers literature sorted according to the field of application as, e.g.
      clinical, pharmaceutical, food, environmental, etc.

PMID- 21171119
TI  - Recent advances in enhancing the sensitivity of electrophoresis and
      electrochromatography in capillaries and microchips (2008-2010).
AB  - Capillary electrophoresis has been alive for over two decades now; yet, its
      sensitivity is still regarded as being inferior to that of more traditional
      methods of separation such as HPLC. As such, it is unsurprising that overcoming
      this issue still generates much scientific interest. This review continues to
      update this series of reviews, first published in Electrophoresis in 2007, with
      an update published in 2009 and covers material published through to June 2010.
      It includes developments in the fields of stacking, covering all methods from
      field-amplified sample stacking and large volume sample stacking, through to ITP,
      dynamic pH junction and sweeping. Attention is also given to on-line or in-line
      extraction methods that have been used for electrophoresis.

PMID- 21171120
TI  - Micellar electrokinetic chromatography: A practical overview of current
      methodological and instrumental advances.
AB  - This review highlights recent methodological and instrumental advances in MEKC
      focused on the improvement of this CE technique in routine analyses. As in the
      previous reviews, the present one deals with the last 2 years' most relevant
      methodological contributions for improving sensitivity and resolution in MEKC as
      well as instrumental research related to MS and LIF detection. The most
      widespread approaches are discussed in detail, including enhancements in
      sensitivity arising from the use of on-line sample concentration (stacking,
      sweeping, and a combination of both of these protocols) and improvements in
      resolution, obtained by changing the composition of the BGE (e.g. with additives
      to the aqueous phase or employing alternative micellar phases to classical SDS)
      and using 2-D separation systems. The advantages and restrictions in MS and LIF
      detection as applied to MEKC analysis are also examined, especially in the direct
      coupling of MEKC and MS detection. Finally, some thoughts on potential future
      directions are also considered.

PMID- 21171121
TI  - MEKC as a powerful growing analytical technique.
AB  - This review summarizes the principle and the developments in MEKC in terms of
      separation power, sensitivity, and detection approaches more than 25 years after
      its appearance. Newly used surfactants are mentioned. Classical and new sample
      concentration techniques in MEKC are described. The different detection
      approaches in MEKC with advantages, limitations, and future prospects are also
      discussed. This review highlights the wider application of MEKC in different
      analytical fields. Various recent selected applications of this technique in
      different analytical fields are reported.

PMID- 21171122
TI  - Recent developments in the methodology and application of MEEKC.
AB  - MEEKC is an electrodriven separation technique that utilises the unique
      properties of a microemulsion (ME) as a background electrolyte to achieve
      separation of a diverse range of solutes. MEs are composed of nanometre-sized oil
      droplets suspended in aqueous buffer, which is commonly referred to as oil-in
      water ME. The droplets are stabilised by the presence of both a surfactant and co
      surfactant. The use of water-in-oil MEs in MEEKC has also been investigated. This
      review details the advances in MEEKC-based separations from the period June 2008 
      June 2010. Areas covered include online sample concentration, suppressed
      electroosmosis MEEKC, chiral separations, MEEKC-MS, MEEKC-ICP-MS and ME structure
      characterisation. The review also includes a fundamental introduction to MEEKC,
      along with a review of recent applications.

PMID- 21171125
TI  - On remembering.

PMID- 21171126
TI  - Dissemination of evidence-based psychological treatments for posttraumatic stress
      disorder in the Veterans Health Administration.
AB  - Unlike the post-Vietnam era, effective, specialized treatments for posttraumatic
      stress disorder (PTSD) now exist, although these treatments have not been widely
      available in clinical settings. The U.S. Department of Veterans Affairs (VA) is
      nationally disseminating 2 evidence-based psychotherapies for PTSD throughout the
      VA health care system. The VA has developed national initiatives to train mental
      health staff in the delivery of Cognitive Processing Therapy (CPT) and Prolonged
      Exposure therapy (PE) and has implemented a variety of strategies to promote
      local implementation. In this article, the authors examine VA's national CPT and
      PE training initiatives and report initial patient, therapist, and system-level
      program evaluation results. Key issues, lessons learned, and next steps for
      maximizing impact and sustainability are also addressed.

PMID- 21171127
TI  - Documented combat-related mental health problems in military noncombatants.
AB  - Although combat-related posttraumatic stress disorder (PTSD) has been documented
      for military combatants, little is known about PTSD in noncombatants. Active-duty
      U.S. Air Force noncombatants (N = 5,367) completed a Post-Deployment Health
      Assessment upon return from combat zones in Iraq (n = 4,408) or a noncombat zone
      in Qatar (n = 959). Those deployed to Iraq were significantly more likely to
      report exposure to someone who was wounded or killed (20.8% vs. 6.3%), feeling in
      great danger of being killed at some point during deployment (18.9% vs. 3.5%),
      symptoms of PTSD (4.1% vs. 0.7%), and symptoms of major depression (9.9% vs.
      5.4%). These findings suggest that deployment to a war zone is associated with
      increased mental health problems, even for noncombatants.

PMID- 21171128
TI  - Bedouin wives on the home front: living with men serving in the Israel Defense
      Forces.
AB  - This community-based study examined emotional and somatic symptoms of 129 Bedouin
      women whose husbands serve in the Israel Defense Forces. Wives of men diagnosed
      with posttraumatic stress disorder (PTSD) reported more symptoms than wives of
      men diagnosed with other disorders and wives of men with no diagnosis. Findings
      indicate that not only was PTSD in Bedouin servicemen positively associated with
      their wives' symptoms of posttraumatic stress and depression and somatic
      complaints, but that this relationship was fully mediated by husbands'
      aggression. Unraveling the special circumstances of women from traditional
      backgrounds faced with the devastating effects of husbands' combat-related
      posttraumatic pathology may inform an approach to the concept of vicarious trauma
      that is more specific to non-Western societies.

PMID- 21171129
TI  - Ongoing exposure versus intense periodic exposure to military conflict and terror
      attacks in Israel.
AB  - The manifestation of posttraumatic stress disorder (PTSD) symptoms in two
      clinical samples in Israel (N = 212) was examined. Individuals suffering ongoing
      exposure to shelling were compared with subjects exposed to intense periodic
      exposure. Elevated arousal and avoidance symptoms, but not intrusion were
      reported in the ongoing exposure group. When compared by age, young participants
      in the ongoing exposure group had significantly lower PTSD scores, whereas no
      differences were found between participants among the intense periodic exposure
      age groups. No gender differences in symptoms were found among participants from
      intense periodic exposure, whereas in the other ongoing group the difference was
      in avoidance. Results are discussed in light of past research on exposure to
      terrorism.

PMID- 21171130
TI  - Implementation of CBT for youth affected by the World Trade Center disaster:
      matching need to treatment intensity and reducing trauma symptoms.
AB  - An implementation study of cognitive-behavioral therapies (CBT) was conducted for
      traumatized youth in a postdisaster context. Headed by the New York State Office
      of Mental Health, the study targeted youth (N = 306) ages 5-21 affected by the
      World Trade Center disaster. They received either trauma-specific CBT or brief
      CBT skills depending upon the severity of trauma symptoms. Clinicians were
      trained to deliver these interventions and received monthly consultation. A
      regression discontinuity design was used to assess optimal strategies for
      matching need to service intensity. At 6-months postbaseline, both groups had
      improved. Rate of change was similar despite differences in severity of need. The
      implications for the implementation of evidence-based treatments postdisaster are
      discussed.

PMID- 21171131
TI  - Attention to process and clinical outcomes of implementing a rural school-based
      trauma treatment program.
AB  - The Louisiana Rural Trauma Services Center was established to provide, improve,
      and enhance urgently needed assessment, treatment, crisis management, and
      consultation services for children and adolescents exposed to traumatic events in
      three rural southeastern Louisiana parishes. The purpose of this study is to
      describe the process of implementing the rural school-based trauma treatment
      program and to evaluate its effectiveness in 115 students. Through attention to
      process including the three-tiered approach of relationship building, trauma
      training, and trauma services, the school-based trauma treatment program proved
      effective in reducing trauma symptoms. This study is important to support the
      widespread implementation of school-based mental health services.

PMID- 21171132
TI  - Posttraumatic stress among young urban children exposed to family violence and
      other potentially traumatic events.
AB  - This study examines the relationship between the number of types of traumatic
      events experienced by children 3 to 6 years old, parenting stress, and children's
      posttraumatic stress (PTS). Parents and caregivers provided data for 154 urban
      children admitted into community-based mental health or developmental services.
      By parent and caregiver report, children experienced an average of 4.9 different
      types of potentially traumatic events. Nearly one quarter of the children
      evidenced clinically significant PTS. Posttraumatic stress was positively and
      significantly related to family violence and other family-related trauma
      exposure, nonfamily violence and trauma exposure, and parenting stress.
      Additionally, parenting stress partially mediated the relationship between family
      violence and trauma exposure and PTS. This study highlights the need for early
      violence and trauma exposure screening in help-seeking populations so that
      appropriate interventions are initiated.

PMID- 21171133
TI  - Prevalence of exposure to potentially traumatic events in a healthy birth cohort
      of very young children in the northeastern United States.
AB  - Prevalence estimates of very young children's exposure to potentially traumatic
      events (PTEs) are limited. The study objective was to estimate the lifetime
      prevalence and correlates of noninterpersonal PTEs and violence exposure in a
      representative healthy birth cohort (ages 1-3 years) from an urban-suburban
      region of the United States (37.8% minority, 20.2% poverty). Parents completed 2
      surveys approximately 1-year apart. By 24-48 months of age, the prevalence of
      exposure was 26.3% (14.5% noninterpersonal, 13.8% violence). Exposure was common
      among children living in poverty (49.0% overall, 19.7% noninterpersonal, 33.7%
      violence). The most consistent factors associated with exposure were poverty,
      parental depressive symptoms, and single parenting. Findings underscore the
      potential for prevention and intervention in early childhood to advance public
      health and reduce morbidity.

PMID- 21171134
TI  - Frequency and severity approaches to indexing exposure to trauma: the Critical
      Incident History Questionnaire for police officers.
AB  - The Critical Incident History Questionnaire indexes cumulative exposure to
      traumatic incidents in police by examining incident frequency and rated severity.
      In over 700 officers, event severity was negatively correlated (r(s) = -.61) with
      frequency of exposure. Cumulative exposure indices that varied emphasis on
      frequency and severity-using both nomothetic and idiographic methods-all showed
      satisfactory psychometric properties and similar correlates. All indices were
      only modestly related to posttraumatic stress disorder (PTSD) symptoms. Ratings
      of incident severity were not influenced by whether officers had ever experienced
      the incident. Because no index summarizing cumulative exposure to trauma had
      superior validity, our findings suggest that precision is not increased if
      frequency is weighted by severity.

PMID- 21171135
TI  - Efficacy of exposure therapy for Japanese patients with posttraumatic stress
      disorder due to mixed traumatic events: A randomized controlled study.
AB  - The authors examined the efficacy of Prolonged Exposure (PE) therapy in Japanese
      patients with posttraumatic stress disorder (PTSD). Twenty-four patients (21
      women, 3 men) with PTSD due to mixed trauma were randomly assigned to the PE
      group (PE with or without treatment as usual [TAU]) or the control group (TAU)
      only. The control group received PE after a 10-week period. Intention-to-treat
      analysis showed the PE group achieved significantly greater reduction than the
      control group at posttreatment in either PTSD or depressive symptoms. The control
      group had significantly decreased symptom severity after PE treatment. Symptom
      levels of 19 PE completers in the both groups remained low in 12-month follow-up
      assessments. The study's findings will promote the future dissemination and
      implementation of evidence-based treatment for PTSD in non-Western settings.

PMID- 21171136
TI  - Resource loss, resource gain, and mental health among survivors of Hurricane
      Katrina.
AB  - Prior research has shown that losses of personal, social, and material resources
      resulting from traumatic events significantly contribute to psychopathology.
      Gains of such resources have been shown to have protective effects on posttrauma
      mental health. Few previous studies of resource change, however, have controlled
      for pretrauma mental health. The current study, which included 402 survivors of
      Hurricane Katrina, made use of data collected prehurricane to examine patterns of
      loss and gain and subsequent mental health. The loss of social support, physical
      health, and personal property were shown to significantly affect posthurricane
      psychological distress over and above the effect of prehurricane psychological
      functioning and disaster exposure. Gains in resources showed no effect.
      Implications for practice and policy were discussed.

PMID- 21171137
TI  - Course of posttraumatic stress symptoms over the 5 years following an industrial
      disaster: a structural equation modeling study.
AB  - The present study examined individual latent changes in posttraumatic stress
      disorder (PTSD) symptoms over a 60-month period after an industrial disaster.
      Participants were recruited from survivors of a factory explosion. Participants
      were assessed retrospectively for peritraumatic reactions and acute stress
      symptoms. Posttraumatic stress disorder symptoms were then assessed at 6, 15, and
      60 months. Using structural equation modeling, the authors tested 3 hypotheses of
      individual latent change: stability of PTSD symptoms between 6, 15, and 60
      months; change between 6 and 15 months; and change between 15 and 60 months. Only
      one model provided a good fit suggesting that PTSD symptoms evolved between 6 and
      15 months after trauma exposure and remained stable at the individual level
      thereafter.

PMID- 21171138
TI  - Traumatic stress, affect dysregulation, and dysfunctional avoidance: a structural
      equation model.
AB  - The multivariate relationship between interpersonal trauma, posttraumatic stress,
      affect dysregulation, and various avoidance behaviors was examined in a sample of
      418 trauma-exposed participants from the general population. Structural equation
      modeling indicated that (a) suicidality, substance abuse, dissociation, and
      problematic activities such as self-injury and dysfunctional sexual behaviors
      were all indicators of a robust latent variable, named dysfunctional avoidance,
      (b) accumulated exposure to various types of interpersonal trauma was associated
      with this avoidance factor, and (c) the relationship between trauma and
      dysfunctional avoidance was independently mediated by both posttraumatic stress
      and diminished affect regulation capacity.

PMID- 21171139
TI  - Physiological predictors of posttraumatic stress disorder.
AB  - Studies have assessed relationships between posttraumatic stress disorder (PTSD)
      symptoms and physiological reactivity concurrently; fewer have assessed these
      relationships longitudinally. This study tests concurrent and prospective
      relationships between physiological reactivity (heart rate and skin conductance)
      to a monologue procedure and PTSD symptoms in female assault survivors, tested
      within 1 and 3 months posttrauma. After controlling for initial PTSD and
      peritraumatic dissociation, 3 measures of increased physiological reactivity to
      the trauma monologue at 1 month predicted 3-month PTSD reexperiencing severity.
      Additionally, increased heart rate following trauma and neutral monologues at 1
      month was predictive of 3-month numbing symptoms. Implications for the
      prospective relationship between physiological reactivity to trauma cues and PTSD
      over time are discussed.

PMID- 21171140
TI  - Childhood traumatic stress and obesity in women: the intervening effects of PTSD
      and MDD.
AB  - In this study, symptoms of posttraumatic stress disorder (PTSD) and major
      depressive disorder (MDD) were modeled as intervening variables in the
      relationship between childhood traumatic stress and weight outcomes in civilian
      women in the United States. Of the 148 participants, 72 had current PTSD, 64 had
      current MDD, and 32 had neither disorder. In separate single indirect effect
      models, there were significant indirect effects of both PTSD and depressive
      symptoms on body mass index and waist-hip ratio. When models included both PTSD
      and depressive symptoms, an indirect effect of PTSD symptoms was evident in the
      relationship between childhood traumatic stress and waist-hip ratio.
      Posttraumatic stress disorder may play a particularly important role in the
      development of central adiposity.

PMID- 21171141
TI  - Are posttraumatic stress disorder mental health terms found in SNOMED-CT medical
      terminology.
AB  - The authors sought to evaluate how well the Systematized Nomenclature of Medicine
      Clinical Terms (SNOMED-CT) controlled vocabulary represents terms commonly used
      clinically when documenting posttraumatic stress disorder (PTSD). A list was
      constructed based on the PTSD criteria in the Diagnostic and Statistical Manual
      of Mental Disorders, Fourth Edition (DSM-IV; American Psychiatric Association,
      1994), symptom assessment instruments, and publications. Although two teams
      mapping the terms to SNOMED-CT differed in their approach, the consensus mapping
      accounted for 91% of the 153 PTSD terms. They found that the words used by
      clinicians in describing PTSD symptoms are represented in SNOMED-CT. These
      results can be used to codify mental health text reports for health information
      technology applications such as automated chart abstraction, algorithms for
      identifying documentation of symptoms representing PTSD in clinical notes, and
      clinical decision support.

PMID- 21171142
TI  - In vitro anti HSV-1 and HSV-2 activity of Tanacetum vulgare extracts and isolated
      compounds: an approach to their mechanisms of action.
AB  - Herpes simplex viruses (HSV-1 and HSV-2) are responsible for long-term latent
      infections in humans, with periods of recurring viral replication associated to
      lesions around the lips, eyes, mucous membrane of the oral cavity or the
      genitals. The lack of an effective vaccine, the moderate to high toxicity of the
      available synthetic antiherpes compounds and the appearance of resistant viral
      strains emphasize the need for new inhibitors. Tanacetum vulgare, commonly known
      as tansy, has been used for treating rheumatic pain, skin eruption and diuretic
      conditions as well as an anthelmintic, antihypertensive, stimulant, emmenagogue,
      carminative, antiseptic, antihypertensive, antispasmodic and antioxidant agent.
      The anti HSV-1 activity of tansy aerial parts, ethyl acetate extract and the
      isolated compound parthenolide, has been reported recently. In this work, through
      a comprehensive mechanistic-based antiherpetic activity study, it was revealed
      that constituents other than parthenolide are responsible for the antiviral
      activity of tansy.

PMID- 21171143
TI  - To debrief or not to debrief our heroes: that is the question.
AB  - Psychological debriefing was developed in the 1980s as an approach for use with
      people whose work exposes them to stressful incidents. It aims to help them to
      process the thoughts and emotions arising from their work. Subsequently, several
      randomized controlled trials tested truncated forms of debriefing in a different
      population: primary victims of unexpected trauma. These trials, and particularly
      two in which debriefing appeared to be harmful, led two major reviews to warn
      practitioners not to offer debriefing. Consequently, many organizations have
      stopped providing debriefing to employees who face trauma in their routine work.
      This paper argues that there are at least three reasons for the apparent failure
      of 'debriefing' in the two studies that reported adverse effects. First, the
      'debriefing' did not follow protocol in terms of timing, length, and training and
      independence of the debriefer. Second, the patients who were 'debriefed' reported
      more severe initial symptoms than those who were not. Third, 'debriefing' was
      used with individuals for whom it was not originally intended. Psychological
      debriefing is intended to be used with groups of people who have been briefed
      together before going on to work together in stressful situations. Such groups
      have reported that they find psychological debriefing helpful, and research is
      emerging indicating that appropriate debriefing may indeed benefit these groups.
      We call for reviewers to recognize the limitations of debriefing research and not
      to overgeneralize their conclusions. 

PMID- 21171144
TI  - A retro-inverso alpha-melanocyte stimulating hormone analog with MC1R-binding
      selectivity.
AB  - alpha-melanocyte stimulating hormone (alpha-MSH) is a tridecapeptide fragment of
      pro-opiomelanocortin (POMC) with broad effects on appetite, skin pigmentation,
      hormonal regulation, and potential roles in both inflammation and autoimmunity.
      The use of this peptide as an anti-inflammatory agent is limited by its low
      selectivity between the melanocortin receptors, susceptibility to proteolytic
      degradation, and rapid clearance from circulation. A retro-inverso (RI) sequence
      of alpha-MSH was characterized for receptor activity and resistance to protease.
      This peptide demonstrated surprisingly high selectivity for binding the
      melanocortin receptor 1 (MC1R). However, RI-alpha-MSH exhibited a diminished
      binding affinity for MC1R compared to alpha-MSH. Mapping of the residues critical
      for agonist activity, receptor binding, and selectivity by alanine scanning,
      identified the same critical core tetrapeptide required for the native peptide.
      Modest improvements in affinity were obtained by conservative changes employing
      non-natural amino acids and substitution of the C-terminal sequence with a
      portion of a MC1R ligand peptide previously identified by phage display.
      Recombination of these elements yielded a peptide with an identical K(i) as alpha
      MSH at MC1R and a lower EC(50) in Mel-624 melanoma cells. A number of other
      structural modifications of the RI peptide were found to differ in effect from
      those reported for the L-form alpha-MSH, suggesting a significantly altered
      interaction with the MC1R.

PMID- 21171145
TI  - Two novel antimicrobial peptides from skin secretions of the frog, Rana
      nigrovittata.
AB  - Two novel antimicrobial peptides with similarity to brevinin-2 family are
      purified and characterized from the skin secretions of the frog, Rana
      nigrovittata. Their amino acid sequences were determined as
      GAFGNFLKGVAKKAGLKILSIAQCKLSGTC (brevinin-2-RN1) and
      GAFGNFLKGVAKKAGLKILSIAQCKLFGTC (brevinin-2-RN2), respectively, by Edman
      degradation. Different from brevinin-2, which is composed of 33 amino acid
      residues (aa), both brevinin-2-RN1 and -RN2 contain 30 aa. Five cDNA sequences
      (Genbank accession numbers, EU136465-9) encoding precursors of brevinin-2-RN1 and
      -RN2 were screened from the skin cDNA library of R. nigrovittata. These
      precursors are composed of 72 aa including a predicted signal peptide, an acidic
      spacer peptide, and a mature brevinin-2-RN. Both brevinin-2-RN1 and -RN2 showed
      strong antimicrobial activities against gram-positive and gram-negative bacteria
      and fungi. The current work identified and characterized two novel antimicrobial
      peptides with unique primary structure.

PMID- 21171146
TI  - The dangers in adopting a tissue-engineering-centric agenda: a president's
      perspective.

PMID- 21171147
TI  - 2010 Panel on the biomaterials grand challenges.
AB  - In 2009, the National Academy for Engineering issued the Grand Challenges for
      Engineering in the 21st Century comprised of 14 technical challenges that must be
      addressed to build a healthy, profitable, sustainable, and secure global
      community (http://www.engineeringchallenges.org). Although crucial, none of the
      NEA Grand Challenges adequately addressed the challenges that face the
      biomaterials community. In response to the NAE Grand Challenges, Monty Reichert
      of Duke University organized a panel entitled Grand Challenges in Biomaterials at
      the at the 2010 Society for Biomaterials Annual Meeting in Seattle. Six members
      of the National Academies-Buddy Ratner, James Anderson, Allan Hoffman, Art Coury,
      Cato Laurencin, and David Tirrell-were asked to propose a grand challenge to the
      audience that, if met, would significantly impact the future of biomaterials and
      medical devices. Successfully meeting these challenges will speed the 60-plus
      year transition from commodity, off-the-shelf biomaterials to bioengineered
      chemistries, and biomaterial devices that will significantly advance our ability
      to address patient needs and also to create new market opportunities.

PMID- 21171148
TI  - Sciatic nerve repair by reinforced nerve conduits made of gelatin-tricalcium
      phosphate composites.
AB  - This study proposes a biodegradable GGT composite nerve guide conduit containing
      genipin-cross-linked gelatin and tricalcium phosphate (TCP) ceramic particles in
      peripheral nerve regeneration. The proposed genipin-cross-linked gelatin annexed
      with TCP ceramic particles (GGT) conduit was dark bluish and round with a rough
      and compact surface. Water uptake and swelling tests indicated that the hydrated
      GGT conduit exhibited increased stability with not collapsing or stenosis. The
      GGT conduit had higher mechanical properties than the genipin-cross-linked
      gelatin without TCP ceramic particles (GG) conduit and served as a better nerve
      guide conduit. Cytotoxicity tests revealed that the GGT conduit was not toxic and
      that it promoted the viability and growth of neural stem cells. The experiments
      in this study confirmed the effectiveness of the GGT conduit as a guidance
      channel for repairing a 10-mm gap in rat sciatic nerve. Walking track analysis
      showed a significantly higher sciatic function index score and better toe
      spreading development in the GGT group than in the silicone group 8 weeks after
      implantation. Gross examination revealed that the diameter of the intratubular
      newly formed nerve fibers in GGT conduits exceeded those in silicone tubes after
      the implantation period. Histological observations revealed that the morphology
      and distribution patterns of nerve fibers in the GGT conduits at 8 weeks after
      implantation were similar to those of normal nerves. The quantitative results
      indicated the superiority of the conduits over the silicone tubes. Motor
      functional and histomorphometric assessments demonstrate that the proposed GGT
      conduit is a suitable candidate for peripheral nerve repair.

PMID- 21171149
TI  - Fibrin microthreads support mesenchymal stem cell growth while maintaining
      differentiation potential.
AB  - We developed a method to produce discrete fibrin microthreads, which can be
      seeded with human mesenchymal stem cells (hMSCs) and used as a suture to enhance
      the efficiency and localization of cell delivery. To assess the efficacy of
      fibrin microthreads to support hMSC attachment, proliferation, and survival,
      microthreads (100 MUm diameter per microthread) were bundled together, seeded
      with 50,000 hMSCs for 2 h, and cultured for 5 days. Cell density on microthread
      bundles increased over time in culture to a maximum average density of 731 +/-
      101 cells/mm(2) after 5 days. A LIVE/DEAD assay confirmed that the cells were
      viable, and Ki-67 staining verified hMSC proliferation. In addition, functional
      differentiation assays demonstrated that hMSCs cultured on microthreads retained
      their ability to differentiate into adipocytes and osteocytes. The results of
      this study demonstrate that fibrin microthreads support hMSC viability and
      proliferation, while maintaining their multipotency. We anticipate that these
      cell-seeded fibrin microthreads will serve as a platform technology to improve
      localized delivery and engraftment of viable cells to damaged tissue.

PMID- 21171150
TI  - Polyelectrolyte multilayer film and human mesenchymal stem cells: an attractive
      alternative in vascular engineering applications.
AB  - Mesenchymal stem cells (MSCs) have tremendous potential as a cell source for
      regenerative medicine due to their capacity for differentiation into endothelial
      like cells when seeded on nonmodified cover glasses. This absence of removable
      surface, preventing recovery of cell sheet, constitutes a critical obstacle to
      predict an application in tissue engineering. It remains unknown whether MSCs
      differentiation could be realized when the cells are cultivated on a scaffold
      that could be used in vascular engineering. In this study, we propose to
      differentiate human MSCs into endothelial-like cells on surfaces coated with
      polyelectrolyte multilayer film (PMF) and fibronectin (control surfaces). We
      quantified Platelet Endothelial Cell Adhesion Molecule (PECAM) and von Willebrand
      Factor (vWF) expressions (endothelial cell specific markers) and nitric oxide
      (NO) production, which is representative of the cell functionality. After only
      two weeks of differentiation, we showed, on PMF, that MSCs expressed PECAM and
      vWF, exhibiting a differentiation into endothelial-like cells, which
      functionality was explored by a significant production of nitrites. These results
      highlight the importance of PMF to get human MSCs differentiation and suggest
      that this film of nanometer thickness opens a new route for vascular
      bioengineering by pre-seeding hMSCs directly into a vascular graft functionalized
      by a removable coating.

PMID- 21171151
TI  - Effect of poly(ethylene glycol) diacrylate concentration on network properties
      and in vivo response of poly(beta-amino ester) networks.
AB  - Poly(beta-amino ester) networks have shown promise as tissue scaffolds. The
      objective of this work was to examine the effect of changing poly(ethylene
      glycol) diacrylate concentration on poly(beta-amino ester) network properties and
      to assess the degradable polymers' in vivo response, using magnetic resonance
      imaging (MRI) and immunohistochemistry. The networks were synthesized from
      hexanediol diacrylate (HDDA), poly(ethylene glycol) diacrylate (PEGDA), and a
      primary amine, 3-methoxypropylamine (3-MOPA), with a fixed overall molar ratio of
      diacrylate to amine. Network properties were verified to insure that the networks
      possessed equivalent initial properties and structure other than chemistry. The
      effect of varying PEGDA concentration on water content, mass loss, and modulus
      was determined, where increasing the concentration of PEGDA increases both water
      content, mass loss rate, and decreases modulus. We also show that manipulating
      the network composition at ratios of 0:100, 10:90 and 25:75 (PEGDA:HDDA) does not
      elicit a major inflammatory response to subcutaneous implantation of the networks
      in mice. This work provides a foundation for tailoring poly(beta-amino ester)
      networks, based on degradation rate and modulus, as a means to tune the polymer
      properties for various biomedical applications.

PMID- 21171152
TI  - Biamphiphilic triblock copolymer micelles as a multifunctional platform for
      anticancer drug delivery.
AB  - Novel micelles from biamphiphilic triblock copolymer poly(ethylene glycol)-b
      poly(epsilon-caprolactone)-b-poly(acrylic acid) (PEG-b-PCL-b-PAA) as new
      multifunctional nanocarriers to delivery anticancer drugs were evaluated. The
      well-defined triblock copolymers prepared by controlled polymerizations self
      assembled into micelles in aqueous solution with a hydrodynamic radius of 13 nm
      as obtained by dynamic light scattering (DLS) and a low critical micellization
      concentration of 2.9 * 10(-4) g/L. The hydrophobic PCL cores of micelles were
      applied to load hydrophobic drug doxorubicin and the functional PAA subcoronas
      clung to the micellar core were used to carry cisplatin through covalent
      interaction. The results indicated that two anticancer drugs had been loaded by
      different mechanism either separately or simultaneously. Drug loading content and
      efficiency as well as release profiles were evaluated. Furthermore,
      internalization and cytotoxicity of the anticancer nanoparticles against human
      bladder carcinoma EJ cells were studied. The biamphiphilic triblock copolymer
      micelles provided not only biocompatibility and biodegradability, but also
      abilities for loading single and dual anticancer drugs, indicating that this was
      a useful multifunctional platform for anticancer drug delivery.

PMID- 21171153
TI  - Mechanical properties of cross-linked collagen meshes after human adipose derived
      stromal cells seeding.
AB  - The main goal of this study was to evaluate the potential of collagen meshes
      derived from porcine dermis as scaffolds for repairing pelvic organ prolapses.
      Mechanical properties of collagen meshes with different cross-linking percentages
      before and after Adipose Derived Stromal Cells (ADSC) seeding were studied as
      well as the cell-scaffold interaction. Uniaxial tensile tests of the collagen
      meshes with three different cross-linking percentages (full-, partial-, and
      noncross-linked) were carried out along orthogonal directions. Their mechanical
      properties were studied with the same tests before and after seeding with human
      derived adipose stem cells (ADSC) after 1 and 7 days. Histological analyses were
      performed to determine adhesion and proliferation of ADSC. Significant
      differences in mechanical properties of the unseeded meshes were observed between
      each orthogonal direction independently of the cross-linking percentage. A better
      cell adhesion rate was observed in the cross-linked meshes. An increase in the
      mechanical properties after cell seeding was observed with a direct relation with
      the degree of cross-linking. All meshes analyzed showed a marked anisotropy that
      should be taken into account during the surgical procedure. The cross-linking
      treatment increased cell adhesion and the mechanical properties of the collagen
      meshes after seeding. These results suggest that the mechanical properties of
      this type of collagen mesh could be useful as scaffolds for repair of pelvic
      organ prolapse.

PMID- 21171154
TI  - Effect of endothelial cells on bone regeneration using poly(L-lactide-co-1,5
      dioxepan-2-one) scaffolds.
AB  - Our recent in vitro study demonstrated that endothelial cells (ECs) might
      influence the differentiation of bone marrow stromal cells (BMSCs). Therefore,
      the aim of this study was to describe this effect in vivo, using a rat calvarial
      bone defect model. BMSCs were isolated from femurs of two-donor Lewis rats and
      expanded in alpha-minimum essential medium containing 10% fetal bovine serum. One
      fifth of BMSCs were induced and differentiated into ECs in an Endothelial Cell
      Growth Medium-2 and then characterized by a flow cytometry. The remaining BMSCs
      were cultured in freshly prepared osteogenic stimulatory medium, containing
      dexamethasone, ascorbic acid and beta-glycerophosphate. Either BMSCs alone (BMSC
      group) or co-cultured ECs/BMSCs (CO-group) were seeded into poly(L-lactide-co-1,5
      dioxepan-2-one) [poly(LLA-co-DXO)] scaffolds, cultured in spinner flasks, and
      then implanted into symmetrical calvarial defects prepared in recipient rats. The
      animals were sacrificed after 2 months. The formation of new bone was evaluated
      by radiography and histology and by the expression of osteogenic markers using
      reverse transcriptase-polymerized chain reaction (RT-PCR). To investigate vessel
      formation, histological staining was performed with EC's markers. The
      radiographical and histological results showed more rapid bone formation in the
      CO- than in the BMSC-group. However, the expression of EC's marker was similar on
      both groups by histological analysis after 2 months postoperatively. Furthermore,
      the CO-group exhibited greater expression of osteogenic markers as demonstrated
      by RT-PCR. The results are consistent with the previous in vitro findings that
      poly(LLA-co-DXO) scaffold might be suitable candidate for bone tissue
      engineering. In vivo, bone regeneration was enhanced by a construct of the
      polymer scaffold loaded with co-cultured cells.

PMID- 21171155
TI  - Mineral trioxide aggregate solution inhibits osteoclast differentiation through
      the maintenance of osteoprotegerin expression in osteoblasts.
AB  - Mineral trioxide aggregate (MTA) is a therapeutic, endodontic repair material
      that is reported to exhibit calcified tissue-conductive activity. The aim of this
      study was to investigate whether MTA may prevent osteoclast differentiation in
      vitro. MTA solution, but not other commonly used retrofilling materials, such as
      Dycal, Super-EBA, or intermediate restorative material (IRM) solution, dose
      dependently inhibited osteoclastogenesis in cocultures of mouse bone marrow cells
      (BMCs) with primary osteoblast cells (POBs) induced by 1alpha,25-dihydroxyvitamin
      D(3) [1alpha,25(OH)(2) D(3) ]. Exogenous CaCl(2) medium supplementation did not
      inhibit osteoclastogenesis in cocultures. Furthermore, MTA solution did not
      affect receptor activator of NF-kappaB ligand (RANKL)-induced osteoclastogenesis,
      suggesting that POBs are targets of MTA. MTA solution suppressed the
      1alpha,25(OH)(2) D(3) -induced reduction of osteoprotegerin (OPG) mRNA and
      protein production without changing RANKL expression in POBs. Consistent with
      this result, MTA solution did not inhibit osteoclastogenesis in cocultures of
      BMCs and POBs from OPG-deficient mice. Therefore, the maintenance of OPG
      expression in POBs appears to be critical for the inhibitory effect of MTA
      solution on osteoclast differentiation.

PMID- 21171156
TI  - Ica-expression and gentamicin susceptibility of Staphylococcus epidermidis
      biofilm on orthopedic implant biomaterials.
AB  - Ica-expression by Staphylococcus epidermidis and slime production depends on
      environmental conditions such as implant material and presence of antibiotics.
      Here, we evaluate biofilm formation and ica-expression of S. epidermidis strains
      on biomaterials involved in total hip- and knee arthroplasty [polyethylene (PE),
      polymethylmethacrylate (PMMA), stainless steel (SS)]. Ica-expression, assayed
      using real-time RT-PCR, was highest on PE as confirmed using confocal laser
      scanning microscopy. Yet biofilm formation by S. epidermidis was most extensive
      on SS, with less slime production. Ica-expression and slime production were
      minimal on PMMA. After 3 h of continued growth of 24 h old biofilms in the
      presence of gentamicin, biofilms on PE showed lower susceptibility to gentamicin,
      relative to the other materials, presumably as a result of the stronger ica
      expression. A higher gentamicin concentration further decreased metabolic
      activity on all biomaterials. It is concluded that the level of biomaterial
      induced ica-expression does not correlate with the amount of biofilm formed, but
      initially aids bacteria in surviving antibiotic attacks. Once antibiotic
      treatment has started however, also the antibiotic itself induces slime
      production and only if its concentration is high enough, killing results. Results
      suggest that biomaterial-associated infections in orthopedics by S. epidermidis
      on PE may be more difficult to eradicate than on PMMA or SS.

PMID- 21171157
TI  - Cell culture plastics with immobilized interleukin-4 for monocyte
      differentiation.
AB  - Standard cell culture plastic was surface modified by passive adsorption or
      covalent attachment of interleukin (IL)-4 and investigated for its ability to
      induce differentiation of human monocytes into mature dendritic cells, a process
      dose-dependently regulated by IL-4. Covalent attachment of IL-4 proceeded via
      anthraquinone photochemistry to introduce amine functionalities at the surface
      followed by coupling of IL-4 through a bifunctional amine-reactive linker. X-ray
      photoelectron spectroscopy showed that undesirable multilayer formation of the
      photoactive compound could be avoided by reaction in water instead of phosphate
      buffered saline. Passively adsorbed IL-4 was observed to induce differentiation
      to dendritic cells, but analysis of cell culture supernatants revealed that
      leakage of IL-4 into solution could account for the differentiation observed.
      Covalent attachment resulted in bound IL-4 at similar concentrations to the
      passive adsorption process, as measured by enzyme-linked immunosorbent assays,
      and the bound IL-4 did not leak into solution to any measurable extent during
      cell culture. However, covalently bound IL-4 was incapable of inducing monocyte
      differentiation. This may be caused by IL-4 denaturation or improper epitope
      presentation induced by the immobilization process, or by biological
      irresponsiveness of monocytes to IL-4 in immobilized formats.

PMID- 21171158
TI  - Tailoring immobilization of immunoglobulin by excimer laser for biosensor
      applications.
AB  - The sheltered transfer and immobilization of rabbit anti-human antiserum
      immunoglobulin G (IgG) by matrix-assisted pulsed laser evaporation (MAPLE) are
      reported. The iced targets submitted to laser irradiation consisted of 0.2-2
      mg/mL IgG blended or not with lipid (L-alpha-phosphatidylcholine dipalmitoyl)
      dissolved in distilled water-based saline buffer. Thin IgG coatings were obtained
      at room temperature onto glass, fused silica, or silicon substrates. Ten thousand
      subsequent laser pulses of 0.33, 0.5, or 0.67 J/cm(2) fluence were applied for
      the synthesis of each sample. Morphology and composition of the thin films were
      studied by optical, scanning, and atomic force microscopy and Fourier transformed
      infrared spectrometry. Optical labeling methods such as spectrofluorimetry and
      fluorescence microscopy were selected to verify the biosensor transduction
      principle because of their high sensitivity for detecting low amounts of antigen
      (IgG). Protein immobilization to the substrate surface was demonstrated for all
      obtained structures after immersion in the donkey anti-rabbit secondary antibody
      solution. The IgG transfer and immobilization onto substrates were improved by
      addition of lipid to MAPLE solutions.

PMID- 21171159
TI  - Role of thiol-complex formation in 2-hydroxyethyl- methacrylate-induced toxicity
      in vitro.
AB  - Methacrylate monomers that are found to leach from cured resin-based dental
      materials induce biological effects in vitro. The underlying mechanisms have not
      been fully elucidated although involvement of increased cellular reactive oxygen
      species (ROS) and DNA-damage has been suggested. In this in vitro study we have
      elucidated the impact of a commonly used methacrylate monomer, HEMA, on the level
      and oxidation state of cellular glutathione, intracellular ROS level, as well as
      the formation of complex between HEMA and glutathione. HEMA exposure rapidly led
      to increased level of ROS and reduced level of GSH (reduced form of glutathione).
      Antioxidants effectively counteracted the ROS increase, but had no effect on the
      GSH depletion. No change in glutathione-disulphide (GSSG; oxidized form of
      glutathione) concentration was detected in the HEMA treated cells, showing that
      oxidation of glutathione was not responsible for the reduced GSH concentration.
      Further we demonstrated spontaneous formation of a complex between HEMA and GSH.
      In conclusion, we showed that exposure to HEMA led to drop in cellular
      glutathione level probably caused by complex formation with HEMA. A similar
      covalent binding of HEMA to macromolecules combined with increased level of
      cellular ROS due to lower levels of GSH is suggested to be important factors
      triggering the toxic response.

PMID- 21171160
TI  - Difference between dogs and rats with regard to osteoclast-like cells in calcium
      deficient hydroxyapatite-induced osteoinduction.
AB  - Material-induced osteoinduction is reported in comparatively large animals such
      as dogs and pigs; however, it does not often occur in small animals such as
      rodents. In this study, we implanted porous calcium-deficient hydroxyapatite
      (CDHA) in the dorsal muscles of dogs and rats and compared the two species, with
      emphasis on multinucleated cells, by using hematoxylin and eosin (HE) staining,
      tartrate-resistant acid phosphatase (TRAP) staining, transmission electron
      microscope (TEM) observation, and reverse transcription-polymerase chain reaction
      (RT-PCR). In CDHA extracted from dogs, numerous TRAP-positive multinucleated
      cells were detected after 2 weeks and new bone formation was observed after 4
      weeks. In contrast, in rats, only a small number of TRAP-positive cells were
      detected and no bone formation was observed within 6 weeks. CDHA was more
      degraded in dogs than in rats. TEM observation of the multinucleated cells in
      CDHA extracted from dogs after 3 weeks revealed osteoclast-like features such as
      ruffled borders. However, CDHA extracted from rats did not exhibit osteoclast
      like features. RT-PCR evaluation showed that the expression of cathepsin K was
      higher in dogs than in rats. These results indicate that TRAP-positive cells
      might be one of the main factors responsible for the cross-species difference in
      material-induced osteoinduction.

PMID- 21171161
TI  - Cellular response of RAW 264.7 to spray-coated multi-walled carbon nanotube films
      with various surfactants.
AB  - The increasing role of carbon nanotubes (CNTs) in various biological applications
      has led to a number of studies on the cytotoxicity of solution-phase CNTs, but
      few studies are available concerning the cytotoxicity of CNT films. Herein, we
      studied the potential health effect of CNT films fabricated with three commercial
      surfactants (sodium cholate, sodium dodecyl sulfate, and triton X-100). Multi
      walled carbon nanotube-surfactant dispersions were coated onto substrates through
      air-spray technique. Cellular morphology, MTT assays, as well as the expression
      of TNF-alpha and IL-1beta of RAW 264.7 cells cultured on the spray-coated CNT
      films were evaluated for cytotoxicity. It was found that the cytotoxicity of the
      CNT films was largely dependent on the type of surfactant used and could be
      significantly reduced by mild washing steps.

PMID- 21171162
TI  - Novel tissue-derived biomimetic scaffold for regenerating the human nucleus
      pulposus.
AB  - Numerous scaffold formulations have been investigated to support the regeneration
      of nucleus pulposus (NP) tissue for use as an early-stage therapy for
      intervertebral disc degeneration. Particular attention has focused on recreating
      the biochemical and mechanical properties of the native NP via the incorporation
      of exogenous extracellular matrix (ECM) components or synthetic surrogates. In
      the present study, we describe a novel approach to develop a tissue engineering
      (TE) scaffold comprised acellular porcine NP ECM. Complete decellularization of
      porcine NP was successfully achieved using a combination of chemical detergents,
      ultrasonication, and treatment with nucleases. Resulting NP scaffolds were devoid
      of host-cell remnants and the porcine antigen alpha-Gal. Native NP ECM components
      including aggrecan/chondroitin-6-sulfate and collagens types II, IX, and XI were
      found in physiologically relevant ratios within the NP scaffold. NP scaffold
      swelling capacity and unconfined mechanical properties were not significantly
      different from porcine NP tissue. Furthermore, NP scaffolds were conducive to
      repopulation with human adipose-derived stem cells as cell viability and
      proliferative capacity were maintained. These results demonstrate the successful
      decellularization of porcine NP and the resultant formation of a biomimetic
      scaffold exhibiting potential utility for TE the human NP.

PMID- 21171164
TI  - Gene expression of markers of osteogenic differentiation of human mesenchymal
      cells on collagen I-modified microrough titanium surfaces.
AB  - Microrough, doubly acid etched titanium surfaces (Ti) were further modified by
      amination and covalent coupling of fibrillar collagen type I (ColTi). Human
      Mesenchymal Cells (HMC) adhesion and growth, and relevant osteogenic
      differentiation in nonosteogenic (basal) medium were evaluated by fluorescence
      microscopy, scanning electron microscopy, and RT-PCR for a three-week period.
      Results show strongly enhanced HMC adhesion and cell density at short
      experimental time on ColTi, together with complete spreading of the cell body
      over the microrough surface topography. RT-PCR analysis of several genes involved
      in osteogenesis indicate, since the first week of culturing, significant
      progression of HMC on ColTi along the osteogenic pathway. These results indicate
      that the adopted process of surface immobilization of collagen, mandatory to
      impart collagenase resistance in implant sites, does not impair biospecific
      interactions between HMC and collagen. Thus, it is possible to upgrade properties
      arising from the control of Ti surfaces topography by surface-chemistry driven
      enhanced recruitment of precursor osteogenic cells and pro-osteogenic stimula.

PMID- 21171163
TI  - In vivo performance of a phospholipid-coated bioerodable elastomeric graft for
      small-diameter vascular applications.
AB  - There remains a great need for vascular substitutes for small-diameter
      applications. The use of an elastomeric biodegradable material, enabling acute
      antithrombogenicity and long-term in vivo remodeling, could be beneficial for
      this purpose. Conduits (1.3 mm internal diameter) were obtained by
      electrospinning biodegradable poly(ester urethane)urea (PEUU), and by luminally
      immobilizing a non-thrombogenic, 2-methacryloyloxyethyl phosphorylcholine (MPC)
      copolymer. Platelet adhesion was characterized in vitro after contact with ovine
      blood. The conduits were implanted as aortic interposition grafts in the rat for
      4, 8, 12, and 24 weeks. Surface treatment resulted in a 10-fold decrease in
      platelet adhesion compared to untreated material. Patency at 8 weeks was 92% for
      the coated grafts compared to 40% for the non-coated grafts. Histology at 8 and
      12 weeks demonstrated formation of cellularized neotissue consisting of aligned
      collagen and elastin. The lumen of the grafts was confluent with cells
      qualitatively aligned in the direction of blood flow. Immunohistochemistry
      suggested the presence of smooth muscle cells in the medial layer of the
      neotissue and endothelial cells lining the lumen. Mechanically, the grafts were
      less compliant than rat aortas prior to implantation (4.5 +/- 2.0 * 10(-4) mmHg(
      1) vs. 14.2 +/- 1.1 * 10(-4) mmHg(-1) , respectively), then after 4 weeks in vivo
      they approximated native values, but subsequently became stiffer again at later
      time points. The novel coated grafts exhibited promising antithrombogenic and
      mechanical properties for small-diameter arterial revascularization. Further
      evaluation in vivo will be required to demonstrate complete remodeling of the
      graft into a native-like artery.

PMID- 21171166
TI  - Effects of aqueous environment and surface defects on Arg-Gly-Asp peptide
      adsorption on titanium oxide surfaces investigated by molecular dynamics
      simulation.
AB  - The interactions between Arg-Gly-Asp (RGD) peptides and titanium oxide (TiO(2) )
      surfaces are of considerable interest to medical technological and fundamental
      researchers. In the present study, a molecular dynamics (MD) simulation was used
      to study the interfacial interaction between RGD and TiO(2) at an atomistic
      level. Four important factors affecting RGD adsorption were considered: the
      initial configuration of the RGD, the crystal structure of the TiO(2) materials,
      the presence of surface defects, and a water environment. Three types of RGD
      initial configurations were considered: lying and standing on the N or O end.
      First, RGD adsorptions on ideal rutile (110) and anatase (101) surfaces in a
      vacuum and in a water environment were studied; then the step edge effects were
      considered, and, finally, the synergistic effects of water and surface defects on
      RGD adsorption were investigated. The results from the vacuum indicated that the
      crystal structure of the surface was more important than the initial RGD
      configuration. The interaction between RGD and the anatase (101) surface was
      stronger than that between RGD and the rutile (110) surface according the energy
      analysis. Atomic step edges on TiO(2) surfaces could greatly affect the
      adsorption of the RGD peptide. Water limited the interaction between the RGD
      peptide and the TiO(2) substrate and helped to sustain the initial configuration
      of the former. These findings should be helpful in understanding the RGD-TiO(2)
      interaction mechanisms and should provide useful theoretical guidelines for
      titanium surface treatments in orthopedic applications.

PMID- 21171165
TI  - Enzyme-synthesized poly(amine-co-esters) as nonviral vectors for gene delivery.
AB  - A family of biodegradable poly(amine-co-esters) was synthesized in one step via
      enzymatic copolymerization of diesters with amino-substituted diols. Diesters of
      length C(4) -C(12) (i.e., from succinate to dodecanedioate) were successfully
      copolymerized with diethanolamines with either an alkyl (methyl, ethyl, n-butyl,
      t-butyl) or an aryl (phenyl) substituent on the nitrogen. Upon protonation at
      slightly acidic conditions, these poly(amine-co-esters) readily turned to
      cationic polyelectrolytes, which were capable of condensing with polyanionic DNA
      to form nanometer-sized polyplexes. In vitro screening with pLucDNA revealed that
      two of the copolymers, poly(N-methyldiethyleneamine sebacate) (PMSC) and poly(N
      ethyldiethyleneamine sebacate) (PESC), possessed comparable or higher
      transfection efficiencies compared with Lipofectamine 2000. PMSC/pLucDNA and
      PESC/pLucDNA nanoparticles had desirable particle sizes (40-70 nm) for cellular
      uptake and were capable of functioning as proton sponges to facilitate endosomal
      escape after cellular uptake. These polyplex nanoparticles exhibited extremely
      low cytotoxicity. Furthermore, in vivo gene transfection experiments revealed
      that PMSC is a substantially more effective gene carrier than PEI in delivering
      pLucDNA to cells in tumors in mice. All these properties suggest that poly(amine
      co-esters) are promising nonviral vectors for safe and efficient DNA delivery in
      gene therapy.

PMID- 21171167
TI  - Biomimeticity in tissue engineering scaffolds through synthetic peptide
      modifications-altering chemistry for enhanced biological response.
AB  - Biomimetic and bioactive biomaterials are desirable as tissue engineering
      scaffolds by virtue of their capability to mimic natural environments of the
      extracellular matrix. Biomimeticity has been achieved by the incorporation of
      synthetic short peptide sequences into suitable materials either by surface
      modification or by bulk incorporation. Research in this area has identified
      several novel synthetic peptide segments, some of them with cell-specific
      interactions, which may serve as potential candidates for use in explicit tissue
      applications. This review focuses on the developments and prospective directions
      of incorporating short synthetic peptide sequences onto scaffolds for tissue
      engineering, with emphasis on the chemistry of peptide immobilization and
      subsequent cell responses toward modified scaffolds. The article provides a
      decision-tree-type flow chart indicating the most probable cellular events on a
      given peptide-modified scaffold along with the consolidated list of synthetic
      peptide sequences, supports as well as cell types used in various tissue
      engineering studies, and aims to serve as a quick reference guide to peptide
      chemists and material scientists interested in the field.

PMID- 21171168
TI  - Self-healing biomaterials.
AB  - The goal of this review is to introduce the biomaterials community to the
      emerging field of self-healing materials, and also to suggest how one could
      utilize and modify self-healing approaches to develop new classes of
      biomaterials. A brief discussion of the in vivo mechanical loading and resultant
      failures experienced by biomedical implants is followed by presentation of the
      self-healing methods for combating mechanical failure. If conventional composite
      materials that retard failure may be considered zeroth generation self-healing
      materials, then taxonomically speaking, first generation self-healing materials
      describe approaches that "halt" and "fill" damage, whereas second generation self
      healing materials strive to "fully restore" the prefailed material structure. In
      spite of limited commercial use to date, primarily because the technical details
      have not been suitably optimized, it is likely from a practical standpoint that
      first generation approaches will be the first to be employed commercially,
      whereas second generation approaches may take longer to implement. For self
      healing biomaterials the optimization of technical considerations is further
      compounded by the additional constraints of toxicity and biocompatibility,
      necessitating inclusion of separate discussions of design criteria for self
      healing biomaterials.

PMID- 21171170
TI  - Simultaneous separation and identification of limonoids from citrus using liquid
      chromatography-collision-induced dissociation mass spectra.
AB  - Limonoids are considered as potential cancer chemopreventive agents and are
      widely distributed in the Citrus genus as aglycones and glucosides. In the
      present study, reversed-phase HPLC coupled with CID mass spectra was developed
      for the simultaneous separation and identification of aglycones and glucosides of
      limonoids from citrus. Five aglycones such as limonin, deacetyl nomilin,
      ichangin, isolimonoic acid and nomilin were identified by positive ion CID MS/MS,
      whereas five glucosides, viz. limonin glucoside, isoobacunoic acid glucoside,
      obacunone glucoside, deacetyl nomilinic acid glucoside and nomilinic acid
      glucoside were analyzed by negative ion CID mass spectra. The developed method
      was successfully applied to complex citrus samples for the separation and
      identification of aglycones and glucosides. Citrus seeds were extracted with
      methanol and partially purified and analyzed by LC-CID mass spectra. The
      separation was achieved by C-18 column; eight limonoids were identified by
      comparing the retention times and mass spectral fragmentation. To the best of our
      knowledge, this is the first report on the identification of citrus limonoids
      using CID technique.

PMID- 21171171
TI  - Development and optimization of an LC-MS/MS-based method for simultaneous
      quantification of vitamin D2 , vitamin D3 , 25-hydroxyvitamin D2 and 25
      hydroxyvitamin D3.
AB  - Simultaneous and accurate measurement of vitamin D and 25-hydroxyvitamin D in
      biological samples is a barrier limiting our ability to define "optimal" vitamin
      D status. Thus, our goal was to optimize conditions and evaluate an LC-MS method
      for simultaneous detection and quantification of vitamin D(2) , vitamin D(3) , 25
      hydroxyvitamin D(2) and 25-hydroxyvitamin D(3) in serum. Extraction and
      separation of vitamin D forms were achieved using acetone liquid-liquid
      extraction and by a reversed phase C8 column, respectively. Detection was
      performed on a triple quadrupole tandem mass spectrometer (QQQ-MS/MS) equipped
      with atmospheric pressure photo ionization source. The LOQs for all analytes
      tested were 1 ng/mL for hydroxylated molecules and 2 ng/mL for the parent vitamin
      Ds. RSD at lower LOQ (2 ng/mL) and in medium (80 ng/mL) and high (200 ng/mL)
      quality control samples did not exceed 20 and 15% CV, respectively. Accuracy of
      the method for determination of hydroxylated molecules was also validated using
      National Institutes of Standards and Technology standard samples and found to be
      in the range of 90.9-111.2%. In summary, a sensitive and reproducible method is
      reported for simultaneous quantification of vitamin D(2) , vitamin D(3) , 25
      hydroxyvitamin D(2) and 25-hydroxyvitamin D(3) molecules in biological samples.

PMID- 21171172
TI  - Selectivity in separation using pi electron-rich stationary phases for the
      comprehensive two-dimensional analysis of cafe espresso.
AB  - The multidimensional high-performance liquid chromatography separations of the
      complex sample matrix found in cafe espresso coffee were completed on the propyl
      phenyl and butyl phenyl columns that contain 3 and 4 carbon atoms in the spacer
      chain, respectively. Phenyl type stationary phases are able to undergo unique pi
      pi interactions with aromatic compounds. Previous works have found that there are
      differences in retention characteristics between these chain lengths and this was
      explored further here. It was found that when analysing the separations by
      quadrants, using a geometric approach to factor analysis and by measuring the
      normalised mean radius, subtle differences in the separations were observed and
      the butyl phenyl phase was more selective for the high to medium polarity
      species. However, there was very little difference in separation behaviour for
      the hydrophobic components within the coffee sample. Overall, the analysis of the
      entire separation showed very little difference.

PMID- 21171173
TI  - Determination of analytes in medical herbs extracts by SPE coupled with two
      dimensional planar chromatography in combination with diode array scanning
      densitometry and HPLC-diode array detector.
AB  - The purpose of this study is to demonstrate an application of 2-D high
      performance planar chromatography-diode array detector (DAD) and HPLC-DAD after
      solid-phase extraction (SPE) for identification and quantitative analysis of
      pesticides (isoproturon, aziprotryne, hexazinone, flufenoxuron,
      methabenzthiazuron, procymidone, and alpha-cypermethrin) in Melissa officinalis
      L. (Labiatae) samples. The procedure described for the determination of compounds
      is inexpensive and can be applied to routine analysis of analytes in medical
      herbs' samples after preliminary cleanup and concentration by SPE. Average
      recoveries on C18 SPE cartridges of pesticides eluted with 5 mL tetrahydrofuran
      by the proposed HPLC-DAD method, before and after 2-D-high-performance planar
      chromatography separation of analytes from M. officinalis L. samples spiked with
      pesticide at a concentration level of 10 MUg/g in plant material are presented.
      Method validation parameters for the quantification of pesticides by the proposed
      HPLC-DAD after SPE method are also presented.

PMID- 21171174
TI  - Validation of a novel LC-MS/MS method for the quantitation of colistin A and B in
      human plasma.
AB  - A liquid chromatography/tandem mass spectrometry (LC-MS/MS) method, characterized
      by complete automation and high-throughput, was developed for the determination
      of colistin A and B in human plasma. All sample preparation procedures were
      performed by using 2.2 mL 96-deep-well plates, whereas robotic liquid-handling
      workstations were utilized for all liquid transfer steps, including solid-phase
      extraction (SPE). The whole preparation procedure was very rapid, whereas the
      method had a very short chromatographic run time of just 2 min. Sample analysis
      was performed by reversed phase LC-MS/MS, with positive electrospray ionization,
      using multiple reaction monitoring. The absence of available purified colistin A
      and B standards led to the development of a novel LC method with evaporative
      light-scattering detector for the determination of their stoichiometries in the
      standard mixture, along with its purity. The proposed bioanalytical method was
      fully validated and it was proven to be selective, accurate, precise,
      reproducible and suitable for the determination of colistin A and B in human
      plasma. It was applied successfully to a pharmacokinetic study for the
      determination of both analytes in samples of patients.

PMID- 21171175
TI  - Preparation and characterization of magnetic chitosan microsphere sorbent for
      separation and determination of environmental estrogens through SPE coupled with
      HPLC.
AB  - In this paper, a new separation sorbent of magnetic chitosan microsphere was
      prepared by means of suspension process using magnetic-Fe(3)O(4) nanoparticles as
      magnetic material and glutaraldehyde as the cross-linker. The morphology and
      properties of magnetic chitosan microspheres were characterized by FT-IR, SEM and
      adsorption test, and the results showed that they had good recognition, high
      selective ability and fast adsorption-desorption dynamics for estriol (E3),
      17beta-estradiol (E2) and diethylstilbestrol (DES). Applying this material as SPE
      sorbent, a method for separation, enrichment and analysis of estrogens in samples
      coupled with HPLC was developed. Under the optimized condition, the detection
      limit (S/N=3) for three estrogens was 3.2-20.1 ng/L, and the RSD for five
      replicate extractions of 50 MUg/L E3, E2 and DES was 4.6-8.3%. The blank river
      water spiked with E3, E2 and DES at 0.05 and 0.2 mg/L levels were extracted and
      determined by the developed method with good recoveries ranging from 85.5 to
      103.7%.

PMID- 21171176
TI  - High-performance purification of quaternary alkaloids from Corydalis yanhusuo W.
      T. Wang using a new polar-copolymerized stationary phase.
AB  - An efficient method for purification of alkaloids from Corydalis yanhusuo W. T.
      Wang using HPLC was developed, featuring a polar-copolymerized stationary phase
      named C18HCE. As ionizable solutes, the crude alkaloid sample often suffered from
      serious peak tailing problem on conventional RP-LC columns, and the separation
      would rapidly became destroyed with the increasing of load amount. However, on
      the new stationary phase, good peak shapes (asymmetry factor <1.5) as well as
      good loadability were easily obtained in a commonly used acidic mobile phase
      condition. The loading amount could reach 10 mg per injection on an analytical
      C18HCE column for laboratory-scale purification. About 6.8 mg of palmatine (HPLC
      purity >98%) and 44.4 mg of dehydrocorydaline (HPLC purity >98%) were rapidly
      derived from 200 mg of the crude alkaloid sample, and the recoveries of these two
      compounds were 76.5 and 81.7%, respectively. The purified alkaloids were
      characterized by comparing retention times with standard compounds as well as
      (1)H-NMR data. The new method is simple and high yielding, and it may provide a
      promising tool for purification of alkaloids as well as other alkaline compounds.

PMID- 21171177
TI  - A weak cation-exchange monolith as stationary phase for the separation of peptide
      diastereomers by CEC.
AB  - A CEC weak cation-exchange monolith has been prepared by in situ polymerization
      of acrylamide, methylenebisacrylamide and 4-acrylamidobutyric acid in a decanol
      dimethylsulfoxide mixture as porogen. The columns were evaluated by SEM and
      characterized with regard to the separation of diastereomers and alpha/beta
      isomers of aspartyl peptides. Column preparation was reproducible as evidenced by
      comparison of the analyte retention times of several columns prepared
      simultaneously. Analyte separation was achieved using mobile phases consisting of
      acidic phosphate buffer and ACN. Under these conditions the peptides migrated due
      to their electrophoretic mobility but the EOF also contributed as driving force
      as a function of the pH of the mobile phase due to increasing dissociation of the
      carboxyl groups of the polymer. Raising the pH of the mobile phase also resulted
      in deprotonation of the peptides reducing analyte mobility. Due to these
      mechanisms each pair of diastereomeric peptides displayed the highest resolution
      at a different pH of the buffer component of the mobile phase. Comparing the weak
      cation exchange monolith to an RP monolith and a strong cation-exchange monolith
      different elution order of some peptide diastereomers was observed, clearly
      illustrating that interactions with the stationary phase contribute to the CEC
      separations.

PMID- 21171178
TI  - Diaminotrehalose-capped beta-cyclodextrin, a new member of hemispherodextrins:
      synthesis, thermodynamic and spectroscopic characterization and its exploitation
      in chiral electrokinetic chromatography.
AB  - The diaminotrehalose-capped derivative of beta-CD, a new member of
      hemispherodextrins, was synthesized and characterized by NMR spectroscopy. Its
      protonation constants were determined by potentiometry, and the inclusion of both
      the enantiomers of dansyl-phenylalanine was investigated by NMR spectroscopy. Its
      stereoselective properties were exploited in electrokinetic chromatography by
      separating four enantiomeric pairs of dansyl derivatives of amino acids.

PMID- 21171179
TI  - Quantitation of antioxidants in water samples using ionic liquid dispersive
      liquid-liquid microextraction followed by high-performance liquid chromatography
      ultraviolet detection.
AB  - A simple and efficient method, ionic liquid-based dispersive liquid-liquid
      microextraction combined with high-performance liquid chromatography-ultraviolet
      detection (HPLC-UV), has been applied for the extraction and determination of
      some antioxidants (Irganox 1010, Irganox 1076 and Irgafos 168) in water samples.
      The microextraction efficiency factors were investigated and optimized: 1-hexyl-3
      methylimidazolium hexafluorophosphate [C(6)MIM][PF(6)] (0.06 g) as extracting
      solvent, methanol (0.5 mL) as disperser solvent without salt addition. Under the
      selected conditions, enrichment factors up to 48-fold, limits of detection (LODs)
      of 5.0-10.0 ng/mL and dynamic linear ranges of 25-1500 ng/mL were obtained. A
      reasonable repeatability (RSD<=11.8%, n=5) with satisfactory linearity
      (r(2)>=0.9954) of the results illustrated a good performance of the presented
      method. The accuracy of the method was tested by the relative recovery
      experiments on spiked samples, with results ranging from 85 to 118%. Finally, the
      method was successfully applied for determination of the analytes in several real
      water samples.

PMID- 21171180
TI  - Highly efficient proteome analysis with combination of protein pre-fractionation
      by preparative microscale solution isoelectric focusing and identification by
      MURPLC-MS/MS with serially coupled long microcolumn.
AB  - To improve the efficiency of proteome analysis, a strategy with the combination
      of protein pre-fractionation by preparative microscale solution isoelectric
      focusing, peptide separation by MURPLC with serially coupled long microcolumn and
      protein identification by ESI-MS/MS was proposed. By preparative microscale
      solution isoelectric focusing technique, proteins extracted from whole cell
      lysates of Escherichia coli were fractionated into five chambers divided by
      isoelectric membranes, respectively with pH range from 3.0 to 4.6, 4.6 to 5.4,
      5.4 to 6.2, 6.2 to 7.0 and 7.0 to 10.0. Compared to the traditional on-gel IFF,
      the protein recovery could be obviously improved to over 95%. Subsequently, the
      enriched and fractionated proteins in each chamber were digested, and further
      separated by a 30-cm long serially coupled RP microcolumn. Through the detection
      by ESI-MS/MS, about 200 proteins were identified in each fraction, and in total
      835 proteins were identified even with one-dimensional MURPLC-MS/MS system. All
      these results demonstrate that by such a combination strategy, highly efficient
      proteome analysis could be achieved, not only due to the in-solution protein
      enrichment and pre-fractionation with improved protein recovery but also owing to
      the increased separation capacity of serially coupled long MURPLC columns.

PMID- 21171181
TI  - A simple and reliable stir bar sorptive extraction-liquid chromatography
      procedure for the determination of chlorpromazine and trifluoperazine in human
      serum using experimental design methodology.
AB  - A sensitive and reproducible stir bar sorptive extraction and HPLC-UV detection
      method was used for the therapeutic drug monitoring of chlorpromazine and
      trifluoperazine in human serum. The separation was achieved using a C(18) column.
      The mobile phase consisted of methanol/sodium acetate buffer (pH 4.1; 0.1 M)
      (95:5, v/v) including 0.5% triethylamine. This miniaturized method can result in
      faster analysis, lower solvent consumption and less workload per sample while
      maintaining or even improving sensitivity. In the second part, stir bar sorptive
      extraction/HPLC-UV method was optimized by a chemometrics approach. An
      experimental design was therefore used to evaluate the statistically influential
      and/or interacting factors, among those described in the literature, and to find
      the best extraction and desorption conditions. Optimal sample volume of 1 mL,
      extraction time of 24 min at 31 degrees C with pH 8.1 were obtained in a
      screening 2(5) half fractional factorial design followed by a Box-Behnken design.
      For the desorption conditions, a Box-Behnken design showed that the best
      conditions were 150 MUL mobile phase for 20 min at 50 degrees C. The optimized
      method was repeatable (CV<10%, linear (LOQ-500 ng/mL)), with the LOQs equal to
      0.7 and 1.5 ng/mL for chlorpromazine and trifluoperazine, respectively.

PMID- 21171182
TI  - Dynamic three-phase hollow fiber microextraction based on two immiscible organic
      solvents with automated movement of the acceptor phase.
AB  - Dynamic three-phase hollow fiber liquid-liquid-liquid microextraction (HF-LLLME)
      based on two immiscible organic solvents, with automated movement of organic
      acceptor phase to facilitate mass transfer was introduced for the first time.
      Polycyclic aromatic hydrocarbons were used as model compounds and extracted from
      water and soil samples. The extraction involved filling an 8 cm length of hollow
      fiber with 25 MUL of organic acceptor solvent using a microsyringe, followed by
      impregnation of the pores in the fiber wall with n-dodecane. The fiber was then
      immersed in 20 mL of aqueous sample solution. During extraction, the organic
      acceptor phase was repeatedly moved in the lumen of the hollow fiber by movement
      of the syringe plunger controlled by programmable syringe pump. Following this
      microextraction, 2 MUL of organic acceptor phase was injected into gas
      chromatography-flame ionization detector. This new technique provided up to 554
      fold preconcentration of the analytes under the optimized conditions. Good
      repeatabilities (with RSDs <=8.4%) were obtained. Detection limits were in the
      range of 0.2-0.5 MUg/L. The utilization of the proposed method for extraction of
      the polycyclic aromatic hydrocarbons from different real samples (such as water
      and soil samples) also gave good precision and recovery.

PMID- 21171183
TI  - Analysis of testosterone in human urine using molecularly imprinted solid-phase
      extraction and corona discharge ion mobility spectrometry.
AB  - Analysis of testosterone was accomplished using corona discharge ion mobility
      spectrometry. Molecular imprinted polymer was used for the extraction and pre
      concentration of testosterone. Analytical parameters including precision, dynamic
      range and detection limit were obtained. The linear dynamic range was from 10 to
      250 ng/mL and the limit of detection was 0.9 ng/mL. The proposed method was used
      for analysis of testosterone in urine samples. A urine sample from a 3-year-old
      girl was used as the blank. The RSD was below 10%. The obtained results from the
      method were also compared with the standard method for analysis of testosterone
      using SPE-HPLC analysis. The results demonstrate the accuracy of the method.

PMID- 21171184
TI  - Extraction of naringin from pomelo peels as dihydrochalcone's precursor.
AB  - A new method for the separation of naringin from pomelo peels was investigated by
      using ultrasonic-assisted extraction and macroporous resin purification
      technology. The ultrasonic extraction efficiency was dependent on agent's
      concentration, ratio of sample and solvent and ultrasonic time. Several
      parameters of macroporous resin-purified process, including resin selection,
      initial concentration, concentration of eluted agent and pH, were optimized. The
      experimental results showed that the naringin content in the mature pomelo peels
      was 2.20% and purification rate of naringin was 77.26% under optimum conditions
      of purification. The structure of synthetic naringin dihydrochalcone was
      determined by a series of spectroscopic methods, such as UV, NMR and MS.

PMID- 21171185
TI  - Serum SP-D levels as a biomarker of lung injury in respiratory syncytial virus
      bronchiolitis.
AB  - To evaluate whether SP-D concentration is a useful biomarker of the severity of
      respiratory syncytial virus (RSV) bronchiolitis, we determined SP-D
      concentrations in patients with RSV bronchiolitis with or without chronic heart
      disease. We enrolled 52 patients who had been diagnosed with RSV bronchiolitis
      and required admission to the hospital at the Department of Pediatrics of
      Fukushima Medical University School of Medicine from 2004 through 2005. These
      patients were divided into two groups: Group 1 consisted of patients without any
      underlying disease and Group 2 consisted of patients with chronic heart disease.
      These patients were assigned to one of three categories. Stage A consisted of
      patients without oxygen dosage, Stage B of patients who required oxygen dosage,
      and Stage C of patients required artificial respiration. We evaluated baseline
      characteristics, clinical features, and serum SP-D concentration in Group 1,
      Group 2, and a control group (healthy infants without infection). Mean serum SP-D
      concentrations in patients with RSV bronchiolitis were higher than those in the
      control group (125.8 +/- 49.3 and 44.2 +/- 20.1 ng/ml, respectively). Mean serum
      SP-D concentration was also higher in Group 2 than in Group 1 patients (160.4 +/-
      56.4 and 112.3 +/- 39.4 ng/ml, respectively). Mean serum SP-D concentrations were
      higher in Stage C than in Stages A or B patients, and mean serum SP-D
      concentrations were higher in Stage B than in Stage A. These findings suggest
      that serum SP-D is associated with the severity of RSV bronchiolitis and that it
      may be a useful biomarker for the severity of RSV bronchiolitis.

PMID- 21171187
TI  - Bronchoscopic findings in a child with pandemic novel H1N1 influenza A and
      methicillin-resistant Staphylococcus aureus.
AB  - The spectrum of disease with pandemic novel H1N1 influenza A (2009) virus ranges
      from non-febrile, mild upper respiratory tract infection to severe or fatal
      pneumonia. We report the bronchoscopic findings associated with a fatal case of
      H1N1 influenza A associated with co-infection with methicillin-resistant
      Staphylococcus aureus (MRSA) in a previously healthy child, which were more
      severe than those previously described as associated with seasonal influenza
      infection alone. The severity of the airway pathology seen on bronchoscopy in
      this patient may be due to a unique effect of the H1N1 influenza A virus or may
      be as a result of a destructive synergism between this virus and bacteria such as
      MRSA.

PMID- 21171188
TI  - Aquagenic wrinkling of palms on exposure to alcohol gel.

PMID- 21171186
TI  - High-flow nasal cannula: impact on oxygenation and ventilation in an acute lung
      injury model.
AB  - INTRODUCTION: High-flow nasal cannula therapy (HFNC) has been shown to be more
      effective than continuous positive airway pressure (CPAP) in reducing intubations
      and ventilator days. HFNC likely provides mechanisms to support respiratory
      efficiency beyond application of distending pressure. We reason that HFNC washout
      of nasopharyngeal dead space impacts CO(2) removal along with oxygenation. The
      aim of this study was to demonstrate the flow dependence of CO(2) reduction and
      improved oxygenation during HFNC and the dependence on leak around the nasal
      prongs. MATERIALS AND METHODS: Neonatal piglets (n=13; 2-6 kg) were injured with
      IV oleic acid and supported with HFNC at 2 through 8 L/min. High and low leak
      around the nasal prongs was accomplished by using single and double prong
      cannulae, respectively. Measurement of hemodynamic, respiratory and blood gas
      parameters were made at each setting following 10 min for physiologic
      equilibration. Tracheal pressures were recorded by transmural catheters. RESULTS:
      With HFNC, CO(2) trended downward in a flow-dependent manner independent of leak.
      Oxygenation and tracheal pressures increased in a flow-dependent manner with the
      greatest effect during double prong. At 8 L/min, tracheal pressures did not
      exceed 6 +/- 1 cmH(2) O. CONCLUSIONS: HFNC improves gas exchange in a flow
      dependent manner; double prong had greater impact on O(2;) single prong had
      greater impact on CO(2) elimination.

PMID- 21171193
TI  - Empirical support for a reclassification of eating disorders NOS.
AB  - OBJECTIVE: To explore the empirical support for a reclassification of the eating
      disorders NOS (EDNOS) category. METHODS: In a cross-sectional design eight
      specific subgroups of EDNOS were compared to anorexia nervosa (AN) and bulimia
      nervosa (BN) on interview-based data and questionnaire measures. The sample
      consisted of 965 patients in the age 13-54 years admitted to treatment for an
      eating disorder. RESULTS: According to the DSM-IV 176(18%) presented with AN,
      290(30%) with BN and 499(52%) with EDNOS. Of all EDNOS cases 34% could be
      reclassified as AN or BN. Three specific subgroups emerged as separate diagnostic
      entities. A heterogeneous subgroup of 122 patients (13% of all) was proposed as
      'true' EDNOS. Implications of the results on the DSM-V are discussed.
      CONCLUSIONS: The results support a broader definition of AN and BN and suggest
      subgroups of EDNOS as separate diagnostic entities. This results in a substantial
      reduction of the heterogeneous EDNOS group.

PMID- 21171195
TI  - How and why to screen for CYP2D6 interindividual variability in patients under
      pharmacological treatments.
AB  - Cytochromes P450 are members of a superfamily of hemoproteins that catalyze a
      variety of oxidative reactions in the metabolism of endogenous and exogenous
      hydrophobic substrates. Fifty-eight cytochrome P450 (CYP) isoenzymes belonging to
      18 families have been identified in human cells; the corresponding genes are
      highly polymorphic, and genetic variability underlies interindividual differences
      in drug response. The polymorphisms of CYP2D6 significantly affect the
      pharmacokinetics of about 50% of the drugs in clinical use, which are CYP2D6
      substrates. The number of functional CYP2D6 alleles per genome determines the
      existence of four different phenotypes, i.e. poor, intermediate, extensive, and
      ultrarapid metabolizers. CYP2D6 genetic variants include copy number variations,
      single nucleotide substitutions, frameshift and insertion/deletion mutations.
      This review reports some of the different methodological approaches used to
      screen for CYP2D6 variants and focuses on methods that have improved variation
      detection, from conventional techniques to more recent microarray technology and
      high throughput DNA sequencing. In addition, this review reports some results on
      clinical relevance of CYP2D6 polymorphisms and provides examples of variability
      in drug response associated with interindividual phenotypic differences.

PMID- 21171196
TI  - Poverty and its impact on diseases in sub-Saharan Africa.

PMID- 21171197
TI  - The RESPONSE trial: a simple solution to a pervasive problem?

PMID- 21171199
TI  - Benign prostate hyperplasia: a review of the year's progress from bench to
      clinic.
AB  - PURPOSE OF REVIEW: Therapeutic tools for classic benign prostate hyperplasia
      (BPH) have focused on the dynamic component of obstruction and/or elimination of
      the static component via surgical or pharmaceutical therapies. Unfortunately, an
      exact cause for this disease process has not been identified, but additional
      insight has been achieved. This article presents an update of the BPH literature
      with a special focus on basic science or translational studies concerned with the
      cause of clinically significant BPH with lower urinary tract symptoms (LUTS).
      RECENT FINDINGS: Investigators are exploring connections between BPH with
      clinically significant LUTS, the metabolic syndrome, inflammation, alterations in
      cell signaling, and genetics which in turn has provided additional information
      concerning the pathogenesis, medical therapies as well as surgical therapies.
      SUMMARY: BPH is a chronic, progressive disease with important care implications
      and financial risks to the healthcare system. Continued improvements in length of
      life will demand that we unlock the cause of LUTS secondary to BPH with the goal
      of prevention as the ideal therapy. Studies reported in the last year contributed
      to our understanding of the disease process and provide insight for additional
      studies.

PMID- 21171200
TI  - Recent advances in robot-assisted radical cystectomy.
AB  - PURPOSE OF REVIEW: The prevalence of robot-assisted radical cystectomy is
      steadily increasing. We review the recent literature evaluating this technique as
      a minimally invasive alternative to open radical cystectomy for the treatment of
      bladder cancer. RECENT FINDINGS: Within the last year, numerous robot-assisted
      radical cystectomy case series with larger cohorts have been published, providing
      new insights regarding perioperative morbidity and early oncologic outcomes. With
      appropriate experience, this procedure offers the potential benefits of decreased
      blood loss and transfusion rates, reduced analgesic requirements, and shorter
      hospital stay relative to the open approach. Recent data from a nonrandomized
      study demonstrate fewer postoperative complications with robot-assisted radical
      cystectomy. Short-term oncologic outcomes in the absence of patient selection
      appear to be equivalent to contemporary open radical cystectomy series. A small
      prospective, randomized trial comparing open and robotic radical cystectomy
      demonstrated equivalent lymph node yields. SUMMARY: Robot-assisted radical
      cystectomy is an emerging minimally invasive approach to radical cystectomy.
      Early data suggest potential benefits in perioperative morbidity with equivalent
      short-term oncologic outcomes as compared with open radical cystectomy. Long-term
      follow-up and larger prospective, randomized comparisons with open radical
      cystectomy are needed as this technique continues to be evaluated.

PMID- 21171201
TI  - Living victims of strangulation: a 10-year review of cases in a metropolitan
      community.
AB  - The prevalence of reported domestic violence or intimate partner violence has
      greatly increased, with approximately 1.5 million women violently assaulted
      annually in the United States by an intimate partner. Strangulation is often seen
      in violence against women, including domestic violence cases. Strangulation is
      defined as "a form of asphyxia characterized by closure of the blood vessels or
      air passages of the neck as a result of external pressure on the neck." This is a
      10-year case review of 102 living victims of strangulation who underwent
      medicolegal evaluation at the Clinical Forensic Medicine Program at a State
      Medical Examiner's Office serving Southern Indiana and all of Kentucky. The
      majority of victims (79%) were strangled by an intimate partner, and manual
      strangulation was the most common method (83%). A total of 38 victims (38%)
      described a history of domestic violence, and the same number lost consciousness
      while being strangled. Nine (9%) women were pregnant at the time of the attack,
      while 13 (13%) had a history of being sexually abused in addition to being
      strangled. A paucity of cases involved only strangulation, as most of the victims
      were subjected to myriad forms of blunt force trauma which included not only the
      head and neck but also other bodily regions. This is a unique presentation of
      strangulation of living persons as most evidence of strangulation in the forensic
      literature has been derived from postmortem examinations of the victims. This
      comprehensive study discussing the examination of a living strangulation victim
      offers valuable insight into the mechanism and the physical findings involved in
      the strangulation process.

PMID- 21171202
TI  - Fatal ischemic stroke due to dissecting aneurysm of the intracranial arteries
      presenting as sudden unexpected death in childhood.
AB  - Sudden unexpected death is any nontraumatic death in healthy individuals with
      normal activities for age until acute demise. Whereas not uncommon in adults and
      infants, it is considered a rarity in children, with most cases due to infection
      or occult cardiovascular abnormalities. Pathologic intracranial findings are
      rarely found in sudden unexpected death in childhood, with most cases due to
      occult intracranial neoplasms. Cerebral arterial dissection is an uncommon cause
      of arterial ischemic stroke in childhood. Outcome is poor, with more than 20% of
      patients dying. We report 4 cases of sudden unexpected death due to arterial
      ischemic stroke after cerebral arterial dissection in childhood and present a
      review of the literature.

PMID- 21171203
TI  - Natural death in the forensic setting a study and approach to the autopsy
      (reply).

PMID- 21171204
TI  - Rigor mortis or something else?

PMID- 21171205
TI  - Stricter weapons law in Switzerland is the wrong policy prescription for homicide
      suicide.

PMID- 21171207
TI  - Influence of a 6 mT static magnetic field on apoptotic cell phagocytosis depends
      on macrophage differentiation.

PMID- 21171206
TI  - US reviews human trial participant protections.

PMID- 21171208
TI  - Ample evidence exists from human studies that vitamin D reduces the risk of
      selected bacterial and viral infections.

PMID- 21171209
TI  - Liver: new insight into hepatocyte genetic diversity and adaptation to injury.

PMID- 21171210
TI  - Pancreas: high stromal expression of alpha-smooth-muscle actin correlates with
      aggressive pancreatic cancer biology.

PMID- 21171211
TI  - Bilateral inferior rectus muscle dysgenesis with lambda-pattern exotropia and
      blepharoptosis.

PMID- 21171212
TI  - Biliary tract: a new duct-to-duct reconstruction technique reduces biliary
      complications in LDLT.

PMID- 21171213
TI  - Barrett esophagus: acetic acid dye spray shows efficacy for detecting neoplasia.

PMID- 21171214
TI  - Paediatric neurointensive care and decompressive craniectomy for malignant middle
      cerebral artery infarction.

PMID- 21171215
TI  - Clostridium difficile: the importance of toxin A is re-established in Clostridium
      difficile infection.

PMID- 21171216
TI  - The contribution of spasticity to the movement disorder of cerebral palsy using
      pathway analysis: does spasticity matter?

PMID- 21171217
TI  - Crohn's disease: soluble plant fibers may protect against E. coli translocation.

PMID- 21171218
TI  - Prevalence of speech and communication disorders in children with CP.

PMID- 21171219
TI  - Endoscopy: acoustic lubrication reduces pain and discomfort associated with
      nasogastric intubation.

PMID- 21171220
TI  - Should we use light-emitting diode photomodulation to minimize radiation-induced
      dermatitis?

PMID- 21171221
TI  - Practical value of measuring compression pressure.

PMID- 21171222
TI  - A message worth repeating: get vaccinated to stop the spread of influenza.

PMID- 21171223
TI  - Racism and health in New Zealand.

PMID- 21171224
TI  - A plea for medical pluralism.

PMID- 21171225
TI  - Advances in biomolecular and medicinal chemistry.

PMID- 21171226
TI  - The ATOLL trial of enoxaparin in primary percutaneous coronary intervention.

PMID- 21171229
TI  - Canada accused of hypocrisy over asbestos exports.

PMID- 21171230
TI  - Music for healing: from magic to medicine.

PMID- 21171231
TI  - A "natural" in the hunt for anticancer compounds. Researcher spans the globe in
      quest for cancer-fighting plants.

PMID- 21171232
TI  - Stage of breast cancer at diagnosis among low-income women with access to
      mammography.
AB  - BACKGROUND: This study assessed the relationship between area-level poverty and
      stage of breast cancer at diagnosis among low-income women when screening
      mammography was available at no cost. METHODS: The authors identified women
      diagnosed with breast cancer from 1999 to 2005 through the Massachusetts Cancer
      Registry, and compared the odds of advanced stage disease for women with low
      incomes (n=546) for whom screening mammography and diagnostic services were
      available at no cost through the Massachusetts Breast and Cervical Cancer Early
      Detection Program, relative to a nonparticipating comparison group (n=1287)
      residing in the same neighborhoods with similar distribution of age, race, and
      ethnicity as Massachusetts Breast and Cervical Cancer Early Detection Program
      participants. Among Massachusetts Breast and Cervical Cancer Early Detection
      Program participants, the odds of advanced stage disease were estimated by
      mammography use. RESULTS: Although screening mammography was available at no
      cost, only 36% of program participants diagnosed with breast cancer used
      screening mammography. Stage of breast cancer at diagnosis was not associated
      with area-level poverty among Massachusetts Breast and Cervical Cancer Early
      Detection Program participants. For the comparison group, advanced stage disease
      was more likely for residents in high-poverty areas, relative to low-poverty
      areas (49% vs 37%, P<.01). The adjusted odds of advanced stage disease at
      diagnosis was greater for women aged 41 to 49 years, compared with those aged 50
      to 64 years (P=.01). CONCLUSIONS: Programs that ensure breast cancer screening
      and diagnostic services are available at no cost to low-income women can mitigate
      the adverse effect of area-level poverty on stage of breast cancer. However, such
      programs require effective strategies to encourage use of screening mammography
      to promote diagnosis at an earlier stage.

PMID- 21171233
TI  - Prolonged brain death duration--does it improve graft quality? Invited commentary
      on Nijboer et al.

PMID- 21171234
TI  - Transfusion medicine as a profession: evolution over the past 50 years.

PMID- 21171235
TI  - Needles in haystacks: the challenges of rare diseases.

PMID- 21171236
TI  - Motor impairment in extremely preterm or low birthweight children.

PMID- 21171237
TI  - Dystrophin and the brain.

PMID- 21171238
TI  - Commentaries on Viewpoint: Do oxidative and anaerobic energy production in
      exercising muscle change throughout growth and maturation? Manifestations of a
      common underlying cause.

PMID- 21171239
TI  - Commentaries on Viewpoint: Do oxidative and anaerobic energy production in
      exercising muscle change throughout growth and maturation? The importance of
      exercise intensity when studying developmental energy metabolism.

PMID- 21171241
TI  - [Cognitive and behavioral consequences of epilepsy during the course of brain
      development].
AB  - The notion that cognitive and behavioural dysfunctions of epileptic origin can be
      prolonged and with an insidious onset, has meant a radical conceptual change
      about epilepsy considered so far uniquely as a paroxysmal disorder. Also, these
      dysfunctions can be the only observable manifestations of the disorder. It is
      particularly true in some epileptic syndromes with onset in childhood. Epileptic
      dysfunctions are characterized by a discontinuity in time (intermittent,
      recurrent), in space (cerebral localization of the dysfunction and its spread).
      They often have a significant relationship with sleep. These features, with
      sometimes the existential dimension of some symptoms (intermittent loss of the
      flux of consciousness, intermittent perceptual distortions or cognitive-emotional
      dysfunction) are not seen in any other congenital or acquired disorders of the
      human brain. Longitudinal clinical studies in which the epileptic variable can be
      directly correlated with the precise study of the cognitive dysfunction (also
      with increasingly complex methods of brain imaging) are a difficult, relatively
      new multidisciplinary task, especially in the very young child. Case examples of
      children followed from early childhood to adulthood will illustrate the diversity
      of observed cognitive and behavioural abnormalities directly caused by the
      epileptic activity which can be massive or very discrete. One is only beginning
      to document precisely the late consequences (or absence of) of some early
      childhood epilepsies that had a direct impact on developing brain function at
      some point.

PMID- 21171242
TI  - [The struggle against AIDS: between new paradigms and inertia].
AB  - Recent statistics on the global HIV epidemic illustrate that HIV incidence
      continues to increase and provide stark reminders of the urgent need for new and
      more effective HIV prevention tools. The new paradigm of HIV prevention
      strategies consists on a biomedical approach including circumcision, vaginal
      microbicides, pre and post exposure prophylaxis and the treatment of the infected
      individual. The goal of the ARV therapy is to reach level of plasma HIV
      indetectability. At less than 20c/ml the risk of sexual transmission is equal to
      zero. A mathematical model shows that by universal testing associated with
      immediate therapy the epidemic could be driven towards elimination by the year
      2020. It is anticipated that there will be substantial barriers to making
      biomedical HIV prevention tools available to individuals who are the highest risk
      of infection. Operationalizing biomedical approaches will require tight links
      between HIV testing and treatment programs, as HIV testing will be the common
      entry point for people to receive either biomedical prevention tools or
      treatment.

PMID- 21171243
TI  - [Effects of radiotherapy (external and/or internal) and chemotherapy on female
      fertility].
AB  - The impact of chemotherapy on a woman's fertility depends on her age and the
      types and doses of the drugs used. Alkylating agents have the biggest negative
      impact on ovarian function. A trial is currently examining the use of a GnRH
      agonist to protect ovarian function. The impact of external radiation therapy and
      brachytherapy on the ovaries depends on three factors: the patient's age, the
      dose delivered to the ovaries, and concurrent use of chemotherapy. Ovarian
      transposition is a simple surgical procedure that can be used in selected cases
      to reduce the risk of early menopause. Both external and internal radiation has
      an impact on the uterus, notably by altering its vascularization and by reducing
      its growth when treatment is delivered during childhood.

PMID- 21171244
TI  - [Infertility treatments after gynecologic cancers and indications of ovarian
      tissue cryopreservation].
AB  - Increasing numbers of young people are surviving cancer, but treatment can affect
      their reproductive function. Female fertility is more difficult to preserve than
      male fertility. Fertility-sparing treatments may be possible for some women. For
      others, embryo cryopreservation is the only established option, provided cancer
      therapy can be postponed. However, cryopreservation of eggs or ovarian tissue is
      now becoming a real possibility. Medically assisted reproductive options for
      cancers survivors include ovarian stimulation, IVF and oocyte donation.
      Gestational surrogacy and adoption are other possibilities.

PMID- 21171245
TI  - [Pregnancy after gynecologic or breast cancer].
AB  - Breast cancer often occurs in women of childbearing age, many of whom go on to
      have children. Several studies suggest that pregnancy does not worsen the outcome
      of breast cancer, and that a history of breast cancer does not affect the outcome
      of pregnancy. The timing of pregnancy after breast cancer should take into
      account the risk of recurrence and metastasis. Conservative surgical treatment
      for cervical cancer may increase the risk of late fetal loss or preterm birth.
      Candidates for conservative treatment of ovarian and endometrial cancer must be
      carefully selected, as recurrence during or after pregnancy is not uncommon.

PMID- 21171246
TI  - [Contraceptive methods after gynecological and breast cancer].
AB  - With earlier diagnosis and more effective treatments, more and more women are
      receiving fertility-preserving cancer therapy. Approximately 10% of breast and
      gynecological cancers occur in women under 40, and more than 5 000 French women
      under 45 develop breast cancer each year. While hormonal contraception is contra
      indicated for women with a history of breast or endometrial cancer, it seems to
      have a protective effective in ovarian cancer. Although pregnancy is not contra
      indicated after cancer, it must be planned in a timely manner, meaning that
      appropriate contraception is necessary in the meantime.

PMID- 21171247
TI  - [Eosinophilic inflammation in allergic diseases].
AB  - Tissular eosinophilia is a common feature of IgE-dependent allergic diseases. The
      classical concept links activated Th2 lymphocytes to eosinophil attraction and
      activation. However, comparisons of allergic diseases with non atopic "mirror
      "diseases reveal more complex underlying pathophysiological mechanisms. This
      article explores the links between allergic asthma and intrinsic asthma or asthma
      of the Churg-Strauss syndrome, nasal polyposis, vernal conjunctivitis,
      eosinophilic esophagitis (food allergy-induced or non allergic), DRESS, Ofuji
      disease, and eosinophilic cystitis. The results of recent mechanistic studies
      show that Th2 activation coupled with tissular eosinophilia can no longer be
      considered a hallmark of atopy. Allergic inflammation may depend on Th1
      activation (vernal conjunctivitis, DRESS, eosinophilic esophagitis, etc) and
      simultaneous viral infection, eliciting drug hypersensitivity (DRESS). A
      predominant role of the epithelium in eosinophil attraction is an alternative
      concept with a sound basis in eosinophilic esophagitis. This concept could lead
      to new therapeutics aimed at controlling epithelial eotaxin 3 expression.

PMID- 21171248
TI  - [New insights into hypereosinophilic syndromes].
AB  - Hypereosinophilic syndrome (HES) is characterized by chronic unexplained
      eosinophilia with organ involvement. The concept of HES as a single disease
      entity is being challenged by the recent identification of multiple underlying
      molecular mechanisms. HES can directly affect the eosinophil lineage (often
      linked to a fusion gene FIP1L1-PDGFRA, and corresponding in this case to chronic
      eosinophilic leukemia), or the lymphoid lineage, where eosinophilia is secondary
      to expansion of a T cell subset overproducing interleukin-5, a cytokine involved
      in eosinophilopoiesis. These recent discoveries have legitimized the use of
      tyrosine kinase inhibitors such as imatinib, which, by inhibiting PDGFRA, have
      transformed the prognosis of chronic eosinophilic leukemia, and also the use of
      monoclonal anti-IL-5 antibodies, which are promising treatment for steroid
      dependent HES.

PMID- 21171249
TI  - [Epidemiology of parasitic diseases, hypereosinophilia, IgE from tropical and
      European parasitological origins].
AB  - Etiologic investigations of hypereosinophilia, often accompanied by IgE
      elevation, depends on the patient's geographic origin and travel history. In
      France, helminth diseases are the only parasitoses associated with
      hypereosinophilia. Some, such as oxyurosis in children, are frequent but
      generally mild. More severe but less frequent infections include distomatoses,
      trichinellosis, taeniasis, echinococcosis and visceral larva migrans. Among
      subjects originating from or having travelled to tropical areas with poor
      hygiene, eosinophilia may be due to early intense polyparasitism and has little
      etiologic value. In Gabon, a warm, humid country in equatorial Africa,
      schoolchildren harbor an average of three different parasites capable of inducing
      hypereosinophilia or serum IgE elevation. These children's eosinophil counts
      start to rise at very young age, after weaning and contact with soil, and
      continue to increase rapidly until adulthood. Average values across all age
      groups are 1580 eosinophils/mm3 and 3300 kU IgE/L. Direct diagnosis of chronic
      parasitic infections is often possible in this setting, and specific treatments
      can be prescribed. In contrast, hypereosinophilia has less etiologic significance
      in patients originating from or having travelled to the tropics and who present
      to European parasitology units. Direct examination is rarely positive, and the
      etiologic diagnosis will thus be guided by epidemiologic, clinical and serologic
      findings. These findings are sometimes sufficient to initiate probabilistic
      treatment with albendazole, ivermectin and praziquentel.

PMID- 21171250
TI  - [Mental pain: is it a symptom?].
AB  - The psychiatrist is confronted by a variety of emotional states, ranging from
      sadness to exaltation. The term "psychache "has been used to describe depression
      with melancholic features. But can such mental pain be defined without reference
      to visible lesions or precise physical symptoms? We report pathophysiological
      evidence supporting this concept and show that it has implications for both
      treatment and prognosis. Cognitive studies have shown that the neurological
      substrate of physical pain is also activated by mental pain. Mental pain is
      associated with a risk of suicide and can be improved by analgesics, including
      opiates and ketamine.

PMID- 21171251
TI  - [Psychiatric indications of deep brain stimulation].
AB  - Introduced at the end of the 1980s, high-frequency deep brain stimulation has
      shown its efficacy in several neurological disorders, including Parkinson's
      disease, dystonia and essential tremor, in which cortico-subcortical circuit
      dysfunction is strongly implicated. The existence of psychiatric symptoms in
      patients with these syndromes has led to the use of this technique in psychiatric
      disorders, and especially in severe refractory obsessive-compulsive disorders,
      even though the anatomical target is still controversial. Other potential
      indications include refractory chronic depression.

PMID- 21171252
TI  - [Towards better evaluation of antipsychotic drugs].
AB  - The methodology for evaluating medicinal products is now well established. It is
      based partly on scientific studies provided in support of marketing application,
      and also on less rigorous "real-life" studies conducted in a specific healthcare
      system. The gap between these two methodological perspectives needs to be
      reduced. In the case of antipsychotic drugs, what is needed most is a better
      definition of endpoints for efficacy. Recent studies show that symptomatic
      improvements may enhance patients' insight and, in turn, increase their
      expectations, with a resulting stagnation of their perceived quality of life. The
      results of randomized trials are difficult to extrapolate to everyday clinical
      practice. Epidemiological studies with strict methodologies and conducted by
      independent bodies should be encouraged.

PMID- 21171253
TI  - [Evaluation of behavioral and cognitive therapy in depression].
AB  - Many psychotherapeutic approaches have been developed for depression, among which
      behavioral and cognitive therapies have shown their effectiveness. These short
      term therapies quickly improve symptoms and reduce the relapse rate by around
      30%. This article reviews the main studies of behavioral and cognitive therapy in
      depressed patients. The results are discussed in terms of acceptability,
      feasibility, and efficacy. The study protocols, psychiatric symptoms, and
      endpoints are described. There is now a need to identify which patients are most
      likely to respond to these treatments.

PMID- 21171254
TI  - [Functional topography of the human corpus callosum].
AB  - The concept of a topographical map of the corpus callosum (CC) has emerged from
      lesion studies in humans and from anatomical tracing investigations in other
      mammals. We conducted the first in vivo study aimed at outlining the
      topographical organization of the normal human CC, using non-invasive functional
      magnetic resonance imaging (fMRI). We tested cortical and callosal activation by
      the BOLD effect during simple sensory stimulation (tactile, gustatory and visual)
      and simple motor tasks in 38 volunteers. The axonal organization of callosal
      white matter was also studied in 16/38 subjects, using diffusion tensor imaging
      (DTI) and diffusion tensor tractography (DTT). Activation foci evoked by taste
      stimuli were detected in most subjects in the anterior part of the CC, those
      elicited by motor tasks lay in the central portion of the body of the CC, and
      those elicited by tactile stimulation of different body regions lay in the
      posterior part of the body. Activation foci evoked by visual stimulation were
      seen in the splenium of the CC. Callosal fibers interconnecting the primary
      cortical areas activated by taste stimulation, motor tasks, and tactile and
      visual stimuli were shown by DTT. Anatomical correlates of the BOLD activation
      foci were demonstrated in the CC, with fibers crossing it at the level of the
      genu, anterior and posterior body, and splenium, respectively. This study
      demonstrates for the first time that the functional topographical organization of
      the human CC can be explored by fMRI in vivo. Our findings may have clinical
      implications, especially for neurosurgical planning.

PMID- 21171255
TI  - [Anti-tumoral matrikines: potential interest in oncology].
AB  - The word 'matrikine' designates certain peptides derived from partial degradation
      of extracellular matrix macromolecules and capable of modulating cellular
      activities. Some matrikines have been shown to inhibit tumor progression and/or
      neo-angiogenesis, suggesting they may have therapeutic potential. This review
      examines the main matrikines with anti-tumoral properties, and particularly those
      originating from basement membrane macromolecules. After a brief description of
      their discovery and main characteristics, we discuss their mode of production,
      mechanism of anti-tumor action, and therapeutic potential.

PMID- 21171256
TI  - [Recommendations for blood pressure self measurement].

PMID- 21171257
TI  - [Prostate cancer cell vaccine transfected with 4-1BBL induces anti-tumor immunity
      in vitro].
AB  - OBJECTIVE: To explore the anti-tumor immunity in vitro induced by prostate cancer
      cell vaccine transfected with recombinant adenovirus encoding 4-1BBL in mice.
      METHODS: The replication-deficient adenovirus AdEasy-1 system was used to
      construct recombinant adenovirus Ad-m4-1BBL and Ad-eGFP. The prostate cancer cell
      RM-1 of mice was transfected with Ad-m4-1BBL and Ad-eGFP, and treated with
      mitomycin (MMC) to produce TCV, TCV-Ad-eGFP and TCV-Ad-m4-1BBL, followed by co
      culture with syngeneic murine spleen cells. Then the cytotoxic activity of the
      lymphocytes against RM-1 cells was analyzed with CCK-8 solution, and IL-2 and INF
      gamma were detected by ELISA. RESULTS: The 4-1BBL protein was highly expressed in
      the TCV-Ad-m4-1BBL of the 4-1BBL-transfected mice. TCV-Ad-m4-1BBL significantly
      increased the expressions of IL-2 ([180.24 +/- 2.22] pg/ml) and INF-gamma
      ([1512.46 +/- 23.64] pg/ml) as compared with TCV and TCV-Ad-eGFP (P < 0.05), and
      induced higher RM-1 cell specific cytotoxicity ([34.24 +/- 2.64]%) than the
      latter two ([9.82 +/- 1.48]%) and ([14.65 +/- 3. 21]%), (P < 0.05). But none of
      them exhibited significant cytotoxicity against hepatocellular carcinoma Hepal-6.
      CONCLUSION: The m4-1BBL-expressing prostate cancer cell vaccine can effectively
      induce anti-tumor immune responses.

PMID- 21171258
TI  - [Apigenin affects semen parameters in male mice].
AB  - OBJECTIVE: To explore the effect of apigenin on semen parameters in male mice.
      METHODS: Totally 100 healthy male mice of Kunming strain were randomly divided
      into 5 groups according to the body weight: negative control, solvent control,
      low-dose apigenin, median-dose apigenin and high-dose apigenin, the latter three
      groups given intragastric apigenin at a fixed time every day for 7 and 14 days.
      At 35 days after the first medication, all the mice were killed and detected for
      the sperm motion parameters by computer aided sperm analysis (CASA). RESULTS:
      There were no statistically significant differences in sperm motion parameters,
      density and motility between the negative control and the three apigenin groups
      after 7-day medication. At 14 days, the high-dose apigenin group showed
      remarkable decreases in average path velocity (VAP), straight line velocity
      (VSL), straightness (STR), wobbliness (WOB), the percentage of grade b sperm and
      sperm motility, and a significant increase in beat cross frequency (BCF) as
      compared with the negative control group (P < 0.05). CONCLUSION: Apigenin affects
      sperm motility in male mice to a certain extent.

PMID- 21171259
TI  - [Prevalence of human papillomavirus in the pubic hair follicles of healthy men
      and male patients with genital warts].
AB  - OBJECTIVE: Human papillomavirus (HPV) commonly exists in healthy individuals, but
      its prevalence in the pubic hair follicles is not yet clear, nor is the
      relationship between HPV infection in the pubic hair follicles and the recurrence
      of genital warts in men. This study aimed to investigate HPV infection in the
      pubic hair follicles of healthy men and patients with genital warts, and to look
      into the correlation of HPV infection with recurrent genital warts. METHODS: We
      included in this study 122 healthy men aged 21-80 years and 86 male patients with
      genital warts aged 24-61 years, detected HPV in their pubic hair follicles by
      PCR, and made comparative analysis of the data obtained from the two groups.
      RESULTS: The positive rate of HPV in the pubic hair follicles of the healthy
      males was 17.21% (21/122), including 15 cases of HPV6, 4 HPV11, 1 non-HPV6/11 and
      1 the mixed type (both HPV6 and HPV11), while that of the genital wart patients
      was 32.55% (28/86), including 17 cases of HPV6, 7 HPV11, 2 non-HPV6/11 and 2 the
      mixed type. CONCLUSION: The incidence of HPV infection is higher in patients with
      genital warts than in healthy men, while the types of HPV involved are basically
      the same in the two groups, mainly HPV6 and HPV11.

PMID- 21171260
TI  - [Multiglycosides of Tripterygium wilfordii increase sperm apoptosis in male
      rats].
AB  - OBJECTIVE: To study the effect of multiglycosides of Tripterygium wilfordii (GTW)
      on sperm apoptosis in male rats and its possible mechanisms. METHODS: Sixteen
      male SD rats were equally assigned to two groups to receive GTW and
      carboxymethylcellulose (CMC) intragastrically, both at 20 mg/(kg x d) for 6
      weeks. Then the epididymal sperm was collected for the measurement of the
      apoptosis rate, sperm membrane lipid fluidity and the contents of NO, MDA and SOD
      by flow cytometry and spectrophotometric determination. RESULTS: After 6 weeks of
      medication, the GTW group showed a significant increase in sperm apoptosis and
      contents of NO and MDA (P < 0.01) and a remarkable decrease in sperm membrane
      lipid fluidity (P < 0.05) and SOD content (P < 0.01) as compared with the CMC
      control group. CONCLUSION: GTW can damage sperm membrane lipid peroxidation and
      sperm membrane structure, increase sperm apoptosis, and reduce sperm membrane
      lipid fluidity.

PMID- 21171261
TI  - [Combination of tamsulosin and tolterodine alleviates refractory lower urinary
      tract symptoms in male patients].
AB  - OBJECTIVE: To evaluate and compare the clinical efficacy and safety of the highly
      selective alpha receptor antagonist tamsulosin and its combination with the M
      receptor antagonist tolterodine in the treatment of refractory lower urinary
      tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH).
      METHODS: We included in this study 184 BPH patients with refractory LUTS with the
      disease course of 4 weeks to 2 years, whose LUTS were not alleviated after a
      week's treatment with tamsulosin. The patients were randomly divided into Groups
      A and B, the former (n=89) treated with tamsulosin at 0.2 mg qd and the latter
      (n=95) given tolterodine at 2 mg bid in addition to tamsulosin medication, both
      for 4 weeks. Scores on IPSS, QOL and Qmax were obtained before and after the
      treatment, and the improvement of LUTS evaluated after the medication. RESULTS:
      The tamsulosin group showed no significant differences before and after the
      treatment in the scores on IPSS (13.23 +/- 4.39 vs. 12.21 +/- 4.07), QOL (4.23 +/
      1.27 vs 3.53 +/- 0.95) and Qmax ([12.3 +/- 8.39] ml/s vs. [14.1 +/- 8.62] mls)
      (P > 0.05), while the combination group exhibited significantly higher scores on
      IPSS and QOL and lower score on Qmax after the medication than before it (IPSS:
      14.45 +/- 5.31 vs. 6.56 +/- 2.03, P < 0.05; QOL: 4.45 +/- 0.79 vs. 2.34 +/- 0.73,
      P < 0.05; Qmax: [11.4 +/- 9.21] ml/s vs. [15.5 +/- 8.35] ml/s, P < 0.01). No
      severe complications were found in any of the cases. CONCLUSION: Combination of
      tamsulosin and tolterodine can significantly alleviate refractory LUTS and
      improve QOL without causing serious adverse events in BPH patients.

PMID- 21171262
TI  - [Vinculin and the androgen receptor in prostate cancer: expressions and
      correlations].
AB  - OBJECTIVE: To investigate the expressions of vinculin (VCL) and the androgen
      receptor (AR) in benign prostatic hyperplasia (BPH) and prostate cancer (PCa) and
      analyze their relationship with the clinical stage and pathological grade of PCa
      and the level of PSA. METHODS: We detected the expressions of VCL and AR in 18
      cases of BPH and 38 cases of PCa by immunohistochemistry, analyzed the
      differences of VCL and AR expressions in BPH and PCa in different clinical stages
      and pathological grades of PCa, compared the primary levels of PSA, and studied
      their correlations. RESULTS: The positive rate of VCL was significantly higher in
      PCa than in BPH tissues (P < 0.05), while that of AR showed no significant
      differences between the two groups (P > 0.05). Both the expressions of VCL and AR
      were closely related with the clinical stage and pathological grade of PCa (P <
      0.05), but not with the PSA level (P > 0.05). There was a positive correlation
      between the expressions of VCL and AR in PCa tissues (r = 0.489, P < 0.05).
      CONCLUSION: VCL is expressed differently in BPH and PCa, which may serve as an
      indicator for the differential diagnosis of benign and malignant prostate
      diseases. The expressions of AR and VCL are gradually reduced with the
      progression of PCa, with a positive correlation between them, and could be used
      jointly to evaluate the progression and prognosis of PCa.

PMID- 21171263
TI  - [Contrast-enhanced ultrasonography in the diagnosis of acute experimental
      incomplete testicular torsion].
AB  - OBJECTIVE: To explore the application value of contrast-enhanced ultrasonography
      (CEUS) in the diagnosis of acute experimental incomplete testicular torsion.
      METHODS: Seven incomplete and 1 complete testicular torsion models were
      established in 8 healthy hybrid dogs by twisting unilateral spermatic cord. The
      twisted testes were included in the model group and the healthy ones in the
      control. All the dogs underwent CEUS before, immediately after, and/or 6 hours
      after the torsion, followed by time-intensity curve analysis. RESULTS: The
      arriving time (AT) and the time to peak (TTP) of the contrast agents in the
      bilateral testes were almost coincident, and the peak intensity (PI) and the area
      under the curve (AUC) in the bilateral testes basically the same before the
      torsion. The incompletely torsion testes showed delayed perfusion of contrast
      agents, prolonged AT and 'TP, and decreased PI and AUC as compared with the
      contralateral testes (P < 0.05), while the completely torsion one exhibited no
      perfusion all the time. CONCLUSION: CEUS has a very high application value in the
      diagnosis of acute incomplete testicular torsion.

PMID- 21171264
TI  - [Endourological treatment of aged high-risk patients with benign prostate
      hyperplasia: a report of 283 cases].
AB  - OBJECTIVE: To evaluate the safety and effectiveness of endourological techniques
      in the treatment of benign prostate hyperplasia (BPH) in aged high-risk patients.
      METHODS: We used endourological techniques in the treatment of 283 BPH patients
      aged over 70 years and complicated with hydronephrosis, renal failure, heart
      failure, cerebral infarction, respiratory dysfunction, anemia, diabetes, bladder
      tumor, or prostate weight over 80 g, TURP (transurethral resection of the
      prostate) for 112 cases and PKRP (transurethral plasmakinetic resection of the
      prostate) for the other 171. All the patients were followed up for 1-30 months.
      RESULTS: In the TURP group, the scores on IPSS and QOL were decreased from 27.5
      +/- 2.8, 5.5 +/- 1.0 to 5.8 +/- 1.2, 1.0 +/- 0.5, and the residual urine volume
      (RUV) from (75.0 +/- 20.0) ml to (8.0 +/- 3.0) ml, but the maximal flow rate
      (Qmax) increased from (6.5 +/- 2.0) ml/s to (18.5 +/- 1.5) ml/s (P < 0.05), while
      in the PKRP group, the scores on IPSS and QOL were decreased from 28.2 +/- 2.2,
      5.5 +/- 1.0 to 5.4 +/- 1.6, 1.0 +/- 0.5, and RUV from (80.0 +/- 20.0) ml to (7.0
      +/- 3.0) ml, and Qmax increased from (6.8 +/- 2.1) ml/s to (20.0 +/- 1.5) ml/s (P
      < 0.05). There were no statistically significant differences in IPSS, QOL, Qmax
      and RUV after treatment between the two groups (P > 0.05), but significantly less
      complications were found in the PKRP than in the TURP group (P < 0.05).
      CONCLUSION: Endourological treatment, especially PKRP, with comprehensive
      perioperative preparations, unerring operative skills, well-controlled operation
      time, and intensive postoperative monitoring and nursing, has the advantages of
      high safety, less bleeding, fewer complications and definite effectiveness for
      aged high-risk BPH patients.

PMID- 21171265
TI  - [Frusemide plus doxazosin therapy for nocturia in patients with BPH/LUTS].
AB  - OBJECTIVE: To determine the efficacy and safety of a diuretic agent, frusemide,
      combined with doxazosin in the treatment of nocturia in patients with benign
      prostate hyperplasia / lower urinary tract symptoms (BPH/LUTS). METHODS: Sixty
      four BPH/LUTS patients with nocturia were equally randomized into two groups, one
      treated with doxazosin (4 mg/d), and the other with frusemide (40 mg/d) and
      doxazosin (4 mg/d), given 6 h before sleep, both for 4 weeks. Urine volume, IPSS,
      QOL, serum electrolytes, plasma osmolality were recorded and compared between the
      two groups before and after the treatment. RESULTS: Compared with the doxazosin
      group, the frusemide plus doxazosin group showed significantly reduced nocturia
      frequency (P < 0.01), increased daytime urine output (P < 0.01), decreased
      nocturia urine output (P < 0.01), unchanged total urine output (P > 0.05),
      improved IPSS and QOL (P < 0.05, P < 0.01), but with no remarkable differences in
      the levels of serum sodium, potassium, chlorine, and osmotic pressure (P > 0.05).
      CONCLUSION: Four-week treatment with frusemide plus doxazosin was safe and
      effective for nocturia in patients with BPH/LUTS.

PMID- 21171266
TI  - [Expression of Chk1 in human sperm and its significance].
AB  - OBJECTIVE: To investigate the expression of the Chk1 gene in human sperm and its
      clinical significance. METHODS: We collected 80 semen samples and divided them
      into 4 groups of equal number: normal, oligospermia, asthenozoospermia and
      oligoasthenozoospermia. The Chk1 expression and its relative level were detected
      by Western blot and RT-PCR, sperm DNA damage and gradient changes assessed by DNA
      ladder analysis, and sperm apoptosis determined by Annexin V/PI double staining
      in each group. RESULTS: The Chk1 gene was expressed in all the four groups, but
      with significant differences (P < 0.01); the relative levels of CHK1 protein were
      similar to those of Chk1 mRNA in the normal, oligospermia, asthenozoospermia and
      oligoasthenozoospermia groups, which were 1.00 +/- 0.22, 0.76 +/- 0.10, 0.45 +/-
      0.08 and 0.37 +/- 0.07, respectively. DNA ladder analysis showed a marked DNA
      ladder in the asthenozoospermia and oligoasthenozoospermia groups. Sperm
      apoptosis was markedly increased in the oligospermia, asthenozoospermia,
      oligoasthenozoospermia and 100% graded sperm groups ([ 8.3 +/- 0.60]%, [11.6 +/-
      0.92]%, [12.5 +/- 1.43]% and [17.0 +/- 1.98]%), as compared with the normal group
      ([7.6 +/- 0.34]%) (P < 0.05). CONCLUSION: Chk1 is expressed in human sperm, but
      differently in different semen quality groups. And its expression is correlated
      with sperm DNA damage and apoptosis; its reduction may lead to declined sperm
      repair and increased sperm apoptosis and thus affect semen quality.

PMID- 21171267
TI  - [Congenital adrenal hyperplasia complicated by testicular adrenal rest tumors:
      one-case clinical analysis].
AB  - OBJECTIVE: To investigate the early diagnosis and treatment of congenital adrenal
      hyperplasia (CAH) complicated by testicular adrenal rest tumors (TART). METHODS:
      We retrospectively analyzed the clinical data of 1 case of late-onset CAH
      complicated by TART diagnosed and treated in Xiamen Women and Children Health
      Care Hospital. RESULTS: The patient was a 15 years old boy, short statured and
      dark skinned, with skin pigmentation in the gum and external genital, secondary
      sex characteristics of the adult and irregular tubercles palpable in the
      bilateral testes. Laboratory examinations showed obviously increased levels of
      ACTH, 17-KS, DHEA-S and progesterone and evidently decreased levels of FSH, LH
      and CO. The low-dose dexamethasone suppression test reduced ACTH and DHEA-S to
      normal. Imaging examinations revealed soft tissue density in the bilateral
      adrenal glands, especially on the right, and irregularly increased volume of the
      bilateral testes, particularly on the left, with heterogeneous signals and septas
      and surrounded by the fluid signals. Histopathological examinations showed the
      eosinophilic cytoplasm to be polygon- or round-shaped, interstitium-like cells
      arranged in line, and lipopigment in the endochylema. Immunohistochemical results
      were negative for testicular interstitial cell tumor. The clinical signs of the
      patient were improved after 3 months of dexamethasone treatment, the hyperplastic
      nodules in the left testis decreased obviously and those in the right testis
      disappeared after 6 months, and the hyperplastic nodules in the adrenal glands
      vanished after 9 months. CONCLUSION: Based on the clinical manifestations and the
      results of auxiliary examinations, this case was diagnosed as late-onset CAH
      complicated by TART, which was attributed to the continued surge of ACTH induced
      by corticoadrenal insufficiency. Sufficient dexamethasone treatment could make
      the TART decrease or disappear and the CAH vanish; it could also improve the
      clinical symptoms and bring the laboratory results to normal.

PMID- 21171268
TI  - [Treatment of 58 cases of penile squamous cell carcinoma].
AB  - OBJECTIVE: To search for rational and effective treatments for penile squamous
      cell carcinoma (PSCC). METHODS: We retrospectively analyzed the clinical data of
      58 cases of pathologically confirmed PSCC, focusing on the treatment methods.
      RESULTS: Based on Jackson Staging, 25 of the 58 cases fell into stage I, 18 stage
      II, 11 stage III, and 4 stage IV. Fifty-three of the patients were treated by
      surgery, of whom 43 underwent limited resection of the tumor or partial
      amputation of the penis, and the other 10 received total penis amputation plus
      perineal urethrostomy and clearance of lymphoglandulae iliacae and inguinal lymph
      nodes, with the lymphoglandulae iliacae positive in 1 case and the inguinal lymph
      nodes positive in all. Thirty-seven cases received neoadjuvant hormonal therapy
      (thermotherapy plus chemotherapy) and combined postoperative chemotherapy, 12
      postoperative chemotherapy only, and 4 merely surgery. Five of the total number
      underwent chemotherapy and/or radiotherapy without surgery. The 2-5 years follow
      up of 48 patients found recurrence in 4 cases of partial penis amputation within
      2 years, 4 deaths within 2 years, 7 deaths from 2 to 5 years. The 2- and 5-year
      survival rates were 91.7% and 77.1%, respectively. Ten of the cases were lost in
      follow-up. CONCLUSION: Surgery + neoadjuvant hormonal therapy + postoperative
      chemotherapy and/or radiotherapy is an effective method for PSCC, but whether it
      can reduce the recurrence of PSCC and improve the survival of the patients
      remains to be further studied.

PMID- 21171269
TI  - [Intracytoplasmic morphologically selected sperm injection of testicular sperm:
      clinical outcome in azoospermia patients].
AB  - OBJECTIVE: To assess whether intracytoplasmic morphologically selected sperm
      injection (IMSI) of testicular sperm improves the clinical outcome in patients
      with azoospermia. METHODS: We performed conventional intracytoplasmic sperm
      injection (ICSI) for 66 patients diagnosed with azoospermia and IMSI for another
      39 using testicular sperm selected at high magnification ( x 6000), and
      comparatively analyzed the clinical outcomes of the two techniques. RESULTS:
      There were no statistically significant differences between conventional ICSI and
      IMSI in the rates of pregnancy (51.52% vs. 56.41%) and implantation (30.67% vs.
      35.29%), although the rate of early abortion was lower in the IMSI than in the
      ICSI group (4.50% vs. 11.76%). CONCLUSION: IMSI of testicular sperm may effect a
      lower rate of early abortion than conventional ICSI in patients with azoospermia.

PMID- 21171270
TI  - [Clinical features of benign prostatic hyperplasia complicated by chronic
      prostatitis].
AB  - OBJECTIVE: To explore the clinical characteristics of benign prostatic
      hyperplasia (BPH) complicated by chronic prostatitis (CP). METHODS: A total of
      120 cases of BPH pathologically confirmed after transurethral resection of the
      prostate (TURP) were assigned to a BPH group (n=75) and a BPH + CP group (n=45)
      according to whether they were complicated by CP. The total prostatic volume
      (TPV) and PSA density (PSAD) were calculated and statistically analyzed based on
      the results of transrectal ultrasonography and f-PSA, t-PSA and f-PSA/t-PSA tests
      before surgery. RESULTS: The BPH group showed a significantly upward tendency in
      f-PSA and t-PSA (P < 0.05) with the increase of age or prostate volume, but not
      significantly in PSAD and f-PSA/t-PSA (P > 0.05). In comparison, the BPH + CP
      group exhibited remarkable increases in f-PSA, t-PSA and PSAD (P < 0.05) but not
      in fPSA/t-PSA (P > 0.05). ROC curve analyses of various indexes showed the area
      under the curve to be 0.644, 0.628 and 0.624 for f-PSA, t-PSA and PSAD,
      respectively, all between 0.5 and 0.7. CONCLUSION: BPH is frequently associated
      with CP. Clinically, high f-PSA, t-PSA and PSAD are important but not sure
      indicators of BPH complicated by CP.

PMID- 21171271
TI  - [Compound graft of porcine small intestinal submucosa with Schwann cells to
      reconstruct injured cavernous nerves and restore erectile function].
AB  - OBJECTIVE: To investigate the restoration of rat penile erection by
      reconstructing injured cavernous nerves (CN) with a compound graft prepared from
      porcine small intestinal submucosa (SIS) and Schwann cells (SC). METHODS: SCs
      were cultured in vitro and a compound graft was prepared from the SCs and SIS.
      Thirty-three healthy SD rats were randomly divided into three groups of equal
      number, sham-operation, CN ablation, and SIS + SC graft. Three months after the
      operation, all the rats underwent the apomorphine test, followed by
      immunohistochemical staining of the tissues from the middle part of the corpus
      cavernosum penis. RESULTS: Combined use of mechanical stripping, mixed-enzyme
      digestion, different-speed adhesion, short-term Ara-C and some other methods
      yielded SCs of a purity high enough for nerve tissue engineering. The SIS
      prepared by mechanical and chemical methods exhibited a good biocompatibility
      with SCs, which could adhere, grow, propagate and differentiate on its surface.
      The apomorphine test showed that both the rate and frequency of penile erection
      were significantly higher in the SIS + SC graft than in the CN ablation group (P
      < 0.01), but lower than in the sham operation group (P < 0.01). The number of
      nNOS positive nerve fibers in the SIS + SC graft group was significantly
      different from that of the CN ablation (P < 0.01), but both were smaller than
      that of the sham-operation group. CONCLUSION: The compound of SIS with SCs, as a
      nerve graft, can be used to reconstruct injured cavernous nerves, and to some
      extent, restore penile erectile function.

PMID- 21171272
TI  - [Paratesticular embryonal rhabdomyosarcoma: report of 5 cases and review of the
      literature].
AB  - OBJECTIVE: To improve the diagnosis and treatment of paratesticular embryonal
      rhabdomyosarcoma (PER). METHODS: We retrospectively studied the clinical data of
      5 cases of PER treated from 1997 to 2009 and reviewed the relevant literature,
      focusing on its clinical manifestations, diagnosis and treatment. RESULTS: The 5
      cases of PER, 2 involving the spermatic cord, 2 the testis and 1 the tunica
      vaginalis, were all treated by radical orchiectomy. Pathologically, 2 cases were
      classified as stage I, 1 as stage II and 2 as stage IV. Postoperatively, 2 of the
      patients received chemotherapy and the other 3 refused adjunctive therapy. The
      patients were followed up for 6, 12, 18 and 28 months, respectively. Four of them
      remained free from relapse and metastasis, and 1 stage IV patient died of
      multiple metastasis at 6 months. CONCLUSION: Early diagnosis, radical orchiectomy
      and adjunctive chemo- or radio-therapy are effective means to the treatment of
      PER.

PMID- 21171273
TI  - [MicroRNAs and prostate cancer].
AB  - MicroRNAs (miRNAs), with the length of about 22 nucleotides, are a growing family
      of small non-protein-coding RNAs that function as post-transcriptional regulators
      of target genes, involved in multiple processes of life and closely related with
      tumorigenesis. Recently, some aberrantly expressed miRNAs have been discovered in
      the prostate, indicating that miRNA may play a critical role in the molecular
      mechanism of the pathogenesis of prostate cancer. With deeper studies on human
      serum and plasma miRNAs, serum miRNA is promising to be a potential diagnostic
      biomarker for prostate cancer.

PMID- 21171274
TI  - [Clinical efficacy of vardenafil on ED patients with kidney-yang or -yin
      deficiency or liver-qi stasis].
AB  - OBJECTIVE: To study the clinical efficacy of vardenafil on erectile dysfunction
      (ED) patients with kidney-yang deficiency, kidney-yin deficiency or liver-qi
      stasis. METHODS: Based on the syndromes of Traditional Chinese Medicine, 124 ED
      patients were divided into Groups A (kidney-yang deficiency, n=44), B (kidney-yin
      deficiency, n=41) and C (liver-qi stasis, n = 39). All the patients were treated
      with vardenafil at 5 mg daily for 8 weeks, and the therapeutic effects were
      evaluated by comparing the scores on IIEF-5 and Erection Quality Scale (EQS)
      before and after the treatment. RESULTS: After vardenafil treatment, the IIEF-5
      and EQS scores of the ED patients were markedly increased, with statistically
      significant differences among the three groups (P < 0.01). The success rate of
      sexual intercourse was significantly improved in Groups A, B (P < 0.01) and C (P
      < 0.05). And the hardness of penile erection was enhanced by 81.82%, 73.17% and
      43.59% respectively in the three groups of patients. CONCLUSION: Vardenafil is
      more effective for ED patients with kidney-yang or kidney-yin deficiency than for
      those with liver-qi stasis.

PMID- 21171275
TI  - [Standard doses of tadalafil for different ED patients].
AB  - OBJECTIVE: To observe the effects of different doses of tadalafil on ED, and to
      search for appropriate doses for the treatment of different ED patients. METHODS:
      Based on the baseline peak systolic velocity (PSV) of cavernosal arteries, 136 ED
      patients were divided into Groups A (PSV > 15 cm/s), B (PSV > 15 cm/s), C (PSV <
      15 cm/s) and D (PSV <15 cm/s) to receive oral tadalafil at 10 mg (Groups A and C)
      and 5 mg (Groups B and D) on alternate days for 4 weeks. All of them were scored
      on IIEF-5 and detected for PSVs of the bilateral cavernosal arteries by color
      Doppler ultrasonography and intracavernous injection of prostaglandin E1 before
      and after the medication. RESULTS: After 4 weeks of tadalafil treatment, IIEF-5
      scores and PSVs were remarkably improved in all the four groups as compared with
      the baseline (P < 0.01), significantly higher in Group C than in D (P < 0.01),
      but with no significant differences between A and B. CONCLUSION: Oral tadalafil
      can improve PSV and hence penile erection in ED patients either at a low or a
      high dose. To reduce side effects and drug cost, the patients with PSV >15 cm/s
      can be medicated at 5 mg, while those with PSV < 15 cm/s at 10 mg or more on
      alternate days.

PMID- 21171276
TI  - [Highlight on recent capillary electrophoresis research].

PMID- 21171277
TI  - [Quantitative structure-retention relationship model of organic compounds on
      comprehensive two-dimensional gas chromatography by heuristic method].
AB  - The descriptors of organic compounds were calculated by means of semi-empirical
      PM3 method and the quantitative structure-retention relationship model of organic
      compounds on three columns of comprehensive two-dimensional gas chromatography
      were set by heuristic method. The good stability and predictive power of the
      multi-linear model were tested and the results showed the model had good linear
      relationships with all squared correlation coefficients more than 0.88 and each
      standard deviation less than 0.105. The leave-one-out cross-validated squared
      correlation coefficients were corresponding with the squared correlation
      coefficients from the model.

PMID- 21171278
TI  - [Identification of Kweichow Moutai liquor by gas chromatography-mass spectrometry
      fingerprint].
AB  - The fingerprint of Kweichow Moutai liquor was established by gas chromatography
      mass spectrometry (GC-MS) and the similarity of fingerprints was evaluated by the
      fingerprint similarity calculation software designed by Zhejiang University based
      on included angle cosine. One milliliter of liquor sample was mixed with ten
      microliter of 2% n-pentyl acetate solution used as internal standard. One
      microliter of the prepared sample was injected into a GC-MS. The separation was
      performed on an HP-INNOWAX 19091N-113 capillary column. The precision and
      repeatability of the method were good as the relative standard deviation (RSD) of
      intrabatch was less than 5%. A total of 35 characteristic components of Kweichow
      Moutai liquor were identified. The fingerprints of 38 batches of Kweichow Moutai,
      5 Moutai-flavor liquors produced by Kweichow Moutai Company Limited, the same
      manufacturer as Kweichow Moutai, and 12 other brand liquors were compared in
      characteristic components and similarity. The results demonstrated that different
      batches of Kweichow Moutai had good similarity (> or = 0.9), and Kweichow Moutai
      was differentiated from the liquors of different alcohol contents and flavors,
      but it was poorly distinguished from the Moutai-flavor liquors by fingerprint
      similarity calculation software. Therefore, only in combining characteristic
      components and fingerprint similarity results, Kweichow Moutai can be
      distinguished from other liquors. The established method offers technical basis
      for the identification of Kweichow Moutai.

PMID- 21171279
TI  - [Determination of 153 pesticide residues in tea using on-line gel permeation
      chromatography-gas chromatography/mass spectrometry].
AB  - A method was developed for the determination of 153 pesticide residues in tea
      using on-line gel permeation chromatography-gas chromatography/mass spectrometry
      (GPC-GC/ MS). The pesticide residues were extracted with acetonitrile under
      ultrasonic operation, and the extract was first cleaned up with an ENVI-carb
      solid phase extraction column and then separated and detected with the on-line
      GPC-GC/MS system. The recoveries of the method ranged from 73.32% to 117.05% with
      the relative standard deviations (RSDs) from 0.76% to 13.18%. The limits of
      detection and the limits of quantification were 0.0003-0.006 mg/kg and 0.001-0.02
      mg/kg, respectively. This method is simple, rapid and characterized with
      acceptable sensitivity and accuracy to meet the requirements for the analysis of
      multiple pesticide residues in tea.

PMID- 21171280
TI  - [Determination of 16 polycyclic aromatic hydrocarbons in airborne particle
      samples using two-step thermal desorption and gas chromatography-mass
      spectrometry].
AB  - A method for the determination of 16 polycyclic aromatic hydrocarbons (PAHs) in
      airborne particle samples was developed using two-step thermal desorption and gas
      chromatography-mass spectrometry (GC-MS). The thermal desorption conditions and
      GC-MS parameters were optimized. The results showed that the detection limits
      (LODs) of this method varied from 0.14 to 0.42 ng/m3. The average recoveries were
      ranged from 52.7% to 97.9%, and the relative standard deviations (RSD) were
      ranged from 8.0% to 18.4%. The method was applied to analyze 32 collected
      airborne particle samples. In comparison with the traditional method, this method
      can avoid the waste of organic solvents and also shorten the analysis time. It is
      a green method, and beneficial for the environment and the analysts.

PMID- 21171281
TI  - [Determination of five diacylhydrazine insecticide residues in welsh onion using
      high performance liquid chromatography-tandem mass spectrometry].
AB  - A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/ MS)
      method was established for the determination of RH-5849, methoxyfenozide,
      chromafenozide, fufenozide and tebufenozide residues in Welsh onion. The residues
      in Welsh onion were extracted by blending with acetonitrile, concentrated after
      salting out and purified with a Florisil column. The mobile phase was a mixture
      of methanol and water (containing 0.1% formic acid) (60:40, v/v) at a flow rate
      of 0.2 mL/min. The mass spectrometry was operated with electrospray in positive
      ionization mode and five diacylhydrazine insecticides were identified in multiple
      reaction monitoring (MRM) mode. The fragmentation pathways for the main product
      ions were analyzed. No significant matrix effect was found when the five
      diacylhydrazines were detected after the samples were purified by Florisil
      columns. The calibration curves showed good linearity within the concentrations
      of 2-400 microg/L with the correlation coefficients more than 0.999. The
      recoveries of the five diacylhydrazines spiked in Welsh onion were 72.6%-95.5% at
      spiked levels of 0.002-0.2 mg/kg. The relative standard deviations (RSDs) were
      less than 15%. The limit of quantitation (LOQ) was 2 pg/kg for each
      diacylhydrazine. This method is sensitive and accurate in the determination of
      the five diacylhydrazine insecticides in Welsh onion.

PMID- 21171282
TI  - [Determination of cyanuric acid in milk and milk powder by high performance
      liquid chromatography-tandem mass spectrometry].
AB  - A method for the determination of cyanuric acid (CYA) in milk and milk powder was
      developed using high performance liquid chromatography-electrospray ionization
      tandem mass spectrometry (HPLC-ESI MS/MS). The target analyte was extracted from
      samples by acetonitrile, and the proteins were precipitated at the same time. The
      supernatant was cleaned up and enriched with a strong anion exchange column,
      analysed by HPLC-MS/MS with an AX column, and quantified by internal standard
      method. Good linearity was obtained in the range of 50-2000 microg/L. The
      recoveries were all ranged from 97% to 121% at three levels, 200, 500 and 1000
      microg/kg, and the relative standard deviations (RSDs) were all below 4.8%. Limit
      of quantification (LOQ) was 200 microg/kg. The method has high accuracy and
      precision, the operation is fast, easy and suitable for the determination of CYA
      in milk and milk powder.

PMID- 21171283
TI  - [Simultaneous determination of bisphenol A and tetrabromobisphenol A in plastic
      products using high performance liquid chromatography-mass spectrometry].
AB  - A method for the determination of bisphenol A (BPA) and tetrabromobisphenol A
      (TBBP-A) in plastic products using high performance liquid chromatography-mass
      spectrometry (HPLC-MS) was developed with the ultrasonic extraction. The
      conditions of sample pretreatment, chromatography and mass-spectrometry
      parameters were studied systematically. The research showed that the extraction
      of the BPA and TBBP-A can reach a good performance with 20 mL dichloromethane at
      50 degrees C under ultrasonic extraction for 60 min. The BPA and TBBP-A were
      separated and detected using HPLC-MS with the mobile phase of methanol and water.
      The linearity range of the method was 0.1-2.0 mg/L. The detection limits were
      0.01 mg/kg for BPA and 0.02 mg/kg for TBBP-A. The recoveries for the spiked
      samples were 85.4%-97.6%. This method is time-saving, easy-handling, practicable
      and sensitive, and it can be applied to determine the residues of BPA and TBBP-A
      in plastic products.

PMID- 21171284
TI  - [Determination of four triorganotin residues in leather products by ultra
      performance liquid chromatography-tandem mass spectrometry and cation solid-phase
      extraction].
AB  - A confirmative method was developed for the determination of four triorganotins
      (TOTs) included tributyltin (TBT), triphenyltin (TPhT), di-triphenyltin oxide
      (DTPhT), and cyhexatin (CYT) in leather products by cation solid-phase extraction
      (SPE) and ultra performance liquid chromatography-tandem mass spectrometry (UPLC
      MS/MS). The organotin residues were extracted with HCl solution. The ionized
      compounds were purified with SPE. The reconstituted sample solution was analyzed
      by UPLC-MS/MS in positive ion electrospray and multi-reaction monitor (MRM) mode,
      with a UPLC C18 column as the separation column. The limits of quantification
      were 10 microg/kg for TBT, TPhT, DTPhT (calculated as TPhT) and 20 microg/kg for
      CYT. The method was validated at three levels for each compound. The recoveries
      were from 54.1% to 101.4%, and the relative standard deviations (RSD) were
      between 4.3% and 9.8%. The method is simple, reliable and accurate. It can meet
      the requirements of the domestic and international legislations. The method
      adapts to simultaneously confirm the residues of the four TOTs in leather
      products.

PMID- 21171285
TI  - [Purification of monoamine oxidase B from porcine liver].
AB  - Monoamine oxidase B (MAOB) was purified from porcine liver by solubilization with
      lysis buffer containing 1% Triton X-100, precipitation with 20%-50% ammonium
      sulfate, isolation with hydrophobic chromatography and anion exchange
      chromatography. The purification fold was 18.2. The specific activity was 135
      U/mg. The purified enzyme appeared homogeneous by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE), and it had a relative molecular
      mass of about 60,000. The identification of the enzyme was confirmed by high
      performance liquid chromatography-electrospray ionization tandem mass
      spectrometry (HPLC-ESI-MS/MS). As MAOB is a membrane enzyme, a key step to the
      successful purification was the use of Phenyl-Sepharose CL-4B with phenyl density
      of 75.7 micromol/mL. The results showed that this approach could effectively
      isolate MAOB from porcine liver to yield an enzyme with high purity and specific
      activity.

PMID- 21171286
TI  - [Quantitative identification Qijudihuang pill by integrating overall information
      method based on parallel five wavelength high performance liquid chromatographic
      fingerprints].
AB  - Parallel five wavelength high performance liquid chromatographic (PFW-HPLC)
      fingerprints of Qijudihuang Pill (QJDHP) were established. The quality of QJDHP
      was identified based on systematically quantified fingerprint method (SQFM) by
      the integrating overall information method (IOIM). The chromatographic
      fingerprints (CFPs) were developed by reversed-phase (RP) HPLC, in which 51, 49,
      52, 49 and 47 co-existing peaks were marked at 203, 228, 265, 280 and 326 nm,
      respectively, by choosing paeonol (POL) peak as the reference peak. The natural
      weighted method (NWM), average method (AM) and project parameter method (PPM)
      were separately used to integrate the different chemical qualitative and
      quantitative information from different PFW-HPLC fingerprints. By using the IOIM
      based on SQFM, the qualities of DMS2, DMS4, DMS5 and DMS6 (2 grade) were
      identified as very good; DMS1, DMS3 and DMS10, DMS11 (3 grade) as good; DMS9 (4
      grade) as fine; DMS7 (6 grade) as common, in which DMS8 was regarded as moderate
      (5 grade) by the AM and as common (6 grade) by PPM. The qualities of 11 batches
      of QJDHP were identified, in which 8 batches were above the good level, 1 batch
      was fine level and two batches were common level. Therefore AM was the most
      accurate and simple method to integrate all the information. The experimental
      results indicated that the IOIM based on the PFW-HPLC can be effectively used to
      identify qualitatively and quantitatively the quality of Chinese traditional
      medicine from overall information, which is a reliable method and also can
      quantitatively simplify the bountiful information of HPLC-DAD (diode array
      detection) fingerprints. In fact, the comprehensive identification ability of
      IOIM is the most reliable and effective one.

PMID- 21171288
TI  - [On-line sample stacking for the analysis of glycyrrhiza flavonoids by anion
      selective exhaustive injection-sweeping micellar electrokinetic chromatography].
AB  - An on-line preconcentration technique which coupled anion selective exhaustive
      injection (ASEI)-sweeping technology with micellar electrokinetic chromatography
      (MEKC) was used to analyze three glycyrrhiza flavonoids (isoliquiritigenin,
      liquiritigenin and liquiritin) in medicine. The separation conditions were
      optimized in conventional MEKC. The sample matrix, injection time of water and
      injection time of sample were found to be the predominant influences on the
      glycyrrhiza flavonoids stacking. Under optimal conditions, the detection
      sensitivities were improved by 110, 120, 300 times for isoliquiritigenin,
      liquiritigenin and liquiritin, respectively. The limits of detection (LODs) were
      0.015, 0.014, 0.011 mg/L for isoliquiritigenin, liquiritigenin and liquiritin,
      respectively. The recoveries were ranged in 90.6%-107% and relative standard
      deviations (RSDs) were less than 4.5% (n=3). This method was successfully applied
      for the detection of isoliquiritigenin, liquiritigenin and liquiritin in real
      samples.

PMID- 21171287
TI  - [High performance liquid chromatographic fingerprints of triterpene glycosides
      from Stichopus japonicus].
AB  - The fingerprint chromatograms of triterpene glycosides in Stichopus japonicus
      were established for its quality control. The samples were prepared by solid
      phase extraction (SPE). The analysis was performed on a Zorbax SB-C18 column (250
      mm x 4.6 mm, 5 microm) with acetonitrile-water (containing 0.1% phosphoric acid)
      as mobile phase at a flow rate of 1.0 mL/min, and at a column temperature of 30
      degrees C. The detection wavelength was set at 205 nm. Ten different original
      samples were analyzed, and 6 peaks were identified as common fingerprint peaks
      using the similarity evaluation system for the chromatographic fingerprint of
      traditional Chinese medicine (TCM) recommended by State Pharmacopoeia Committee
      of China (Version 2004 A). The similarities of the fingerprints were all greater
      than 0.97. The method is proved to be stable and repeatable and can be utilized
      as a quality control for S. japonicus.

PMID- 21171289
TI  - [Determination of nonnitrogenous organic acids and inorganic anions in sugarcane
      molasses and molasses alcohol waste by ion chromatography with solid-phase
      extraction].
AB  - A method was established for the determination of main nonnitrogenous organic
      acids (including acetic, lactic, succinic, maleic, tartaric, oxalic, fumaric,
      citric, and aconitic acids) and three inorganic anions (Cl-, SO4(2-) and PO4(3-))
      in sugarcane molasses and molasses alcohol waste by ion chromatography with solid
      phase extraction. The diluted sample solution was purified by strong anion
      exchange (SAX) solid-phase extraction (SPE) in a small packed column to remove
      most of sugar, pigment and other interfering matrices. The eluate obtained from
      the column was rinsed with diluted KOH solution and filtered through a 0.45
      microm inorganic membrane, finally separated on an anion column of IonPac AS15
      with the gradient elution of KOH solution and determined with a suppressed
      conductivity detector. The pretreatment and procedures of SPE for separating
      organic acids and inorganic anions from their matrix were investigated. The
      detection limits wee d less than 0.20 mg/L. The relative standard derivations
      were less than 6.7%. The organic acids and inorganic anions in three real samples
      (two sugarcane molasses samples and an alcohol waste sample) were determined, the
      recovery ranges were from 94% to 109%. The method shows good precision and
      linearity.

PMID- 21171290
TI  - [Determination of nucleotides in infant formula milk powder by ion
      chromatography].
AB  - A method was developed for the determination of nucleotides in infant formula
      milk powder by ion chromatography (IC). The separation was performed on an IonPac
      AS16 column with KOH solution as the mobile phase at a flow rate of 1.0 mL/min
      and 25 degrees C. The detection wavelength was set at 260 nm and the sample
      injection volume was 25 microL. There were good linear relationships between the
      mass concentrations and the peak areas of cytidine monophosphate (CMP), adenosine
      monophosphate (AMP), uridine monophosphate (UMP), inosine monophosphate (IMP) and
      guanosine monophosphate (GMP) in the ranges of 0.09-50, 0.06-50, 0.06-50, 0.09
      50, 0.06-50 mg/L, respectively. The limits of detection (S/N = 3) of CMP, AMP,
      UMP, IMP and GMP were 0.03, 0.02, 0.02, 0.03 and 0.02 mg/L, respectively. The
      method has been applied for the determination of the five nucleotides in infant
      formula milk powder with the recoveries of 92.5%-102.4%. This method is rapid,
      simple and suitable for the determination of real samples.

PMID- 21171291
TI  - [Preparation of gentiopicroside from the extract of Swertia mussotii Franch by
      preparative high performance liquid chromatography].
AB  - A new method for isolation of gentiopicroside (GPS) from Swertia mussotii Franch
      with reversed phase preparative high performance liquid chromatography (Pre-HPLC)
      is described. After 95% ethanol extract was obtained with solvent extraction and
      macroporous resin separation, a fraction containing GPS was acquired and
      subjected to Pre-HPLC for isolation of target component. The optimum operation
      parameters were selected as follows: a C18 column (200 mm x 50 mm, 5 microm),
      methanol-0.1% acetic water (30:70, v/v) as the mobile phase at flow rate of 75
      mL/min, the detection wavelength at 254 nm, and the injection volume of 500
      microL at the mass concentration of 225 g/L. The purity of the product was
      detected by HPLC method. The result showed that the purity of product was above
      99%. The effective and rapid method has been successfully applied to the
      preparation of GPS from Swertia mussotii Franch.

PMID- 21171292
TI  - [Determination of robenidine residue in chicken tissues and eggs by high
      performance liquid chromatography].
AB  - A method for the determination of robenidine residue in chicken tissues and eggs
      by high performance liquid chromatography (HPLC) was established. The samples
      were extracted with acetonitrile and purified by an HLB solid-phase extraction
      (SPE) cartridge. The extract was analyzed by HPLC with acetonitrile-0.05 mol/L
      NH4H2PO4 buffer (6:4, v/v, pH 6.5) as the mobile phase. The flow rate of the
      mobile phase was 1.0 mL/min and detection wavelength was 317 nm. There was a good
      linear correlation between the peak areas and the concentrations of robenidine in
      the range of 10-1000 microg/L. The limit of detection (S/N = 3) was 10 microg/L,
      and the limit of quantification (S/N = 10) was 15 microg/kg. The recoveries of
      robenidine were 73.1%-88.7% at the spiked levels of 15, 50 and 100 microg/kg. The
      results demonstrate that the method is easy, fast, sensitive, and suitable for
      the confirmation and quantification of robenidine residue in chicken tissues and
      eggs. The clean-up effect, sensitivity, accuracy and precision can all meet the
      analysis requirement.

PMID- 21171293
TI  - [Determination of esculeoside A in Lycopersicon esculentum MILL by high
      performance liquid chromatography with evaporative light scattering detection].
AB  - A method for the determination of esculeoside A in Lycopersicon esculentum MILL
      by high performance liquid chromatography (HPLC) with evaporative light
      scattering detection (ELSD) was established. The results showed that esculeoside
      A had good linearity in the range of 0.61-3.05 mg with the correlation
      coefficient of 0. 999 5. The average recoveries were 97.9%-104.8% with the
      relative standard deviations (RSD) < or = 4.14% (n=5). The method is simple,
      sensitive and suitable for the analysis of esculeoside A and quality control for
      the raw material and extract of Lycopersicon esculentum MILL.

PMID- 21171294
TI  - [Serum levels of IL-12, IL-4 and pathologic changes by scanning electron
      microscope of nasal mucous inflammation].
AB  - OBJECTIVE: The serum levels of interleukin-4, interleukin-12 will be detected to
      elucidate and compare the involvement of Th1 and Th2 cells and the surface
      structures of nasal mucosa will also be observed in patients with allergic
      rhinitis (AR), chronic rhinosinusitis with nasal polyps (CRSwNP), chronic
      rhinosinusitis without nasal polyps (CRSsNP) and nasal septal deviation (NSD) to
      obtain the characteristics and regularity of pathological changes. METHOD: The
      serum levels of interleukin-4, interleukin-12 were detected by enzyme linked
      immunosorbent assay method. Four pieces of nasal mucosa on lateral side of middle
      turbinate were sampled from four patients and observed by scanning electron
      microscope. RESULT: The levels of interleukin-4 in AR and NSD groups were
      significantly higher than the healthy controls (P < 0.01). The levels of
      interleukin-4 and interleukin-12 in CRSwNP and CRSsNP groups were both higher
      than the healthy controls (P < 0.01 or P < 0.05), but no differences of the
      interleukin-4 and interleukin-12 levels were found between them (P > 0.05). There
      were two points of regularity with different degrees in our observations: (1)
      disoriented and absence of cilium; (2) the cellular separations at cell junctions
      were obvious, even with cells lost. CONCLUSION: There was an immunologic
      deviation towards Th2 pattern in patients with NSD the same as AR. Both Th1 and
      Th2 with hyperactivity participated in chronic inflammatory process of CRSwNP and
      CRSsNP. The pathological changes of ciliated columnar epithelium in patients with
      the four types of rhinitis, suggest that a comprehensive treatment including
      antral irrigations, multiple antibiotics, topical steroid sprays, or
      antihistamines, as well as nasal surgery to correct nasal deformities should be
      adopted, which can effectively prevent the development and expanding of the nasal
      mucosa inflammation.

PMID- 21171295
TI  - [Resection of the ossifying fibroma of paranasal sinuses and anterior skull base
      with nasal endoscope under the guidance of image navigation].
AB  - OBJECTIVE: To discuss the role of image navigation in resection of the ossifying
      fibroma of paranasal sinuses and anterior skull base with nasal endoscope.
      METHOD: Fourteen cases with ossifying fibroma involving paranasal sinuses and
      anterior skull base were underwent intranasal endoscopic surgery under the
      guidance of image navigation. Sequential nasal sinuses CT scans were obtained
      before and after operation. CT scans demonstrated that the nasal septum, orbital
      wall and anterior skull base were involved in every case. The anterior boundary
      of the frontal recess cells was involved in 10 cases. The lesions were adjacent
      to the orbital apex and optic canal in 5 cases. The sella turcica and clivus were
      invaded in 3 cases and the pterygopalatine fossa was invaded in 2 cases. RESULT:
      The tumors were thoroughly removed in all cases. The average operative time was
      280 minutes and the average registration time of navigation was 9 minutes.
      Postoperation CT scans demonstrated that the tumors were totally resected.
      CONCLUSION: The image-guided endoscopic surgery of the ossifying fibroma of
      paranasal sinuses and anterior skull base provided accurate tumor resection,
      increased surgical effectiveness, decreased overall surgical complications.

PMID- 21171296
TI  - [Mast cell and its relation to eosinophilic inflammation in CRSsNP].
AB  - OBJECTIVE: To observe the pathologic characteristics, and investigate mast cell
      and its activation in chronic rhinosinusitis without nasal polyps (CRSsNP) and
      their relations with eosinophilic inflammation. METHOD: HE stain was used to
      observe tissue features and count total inflammatory cells, mononuclear cells,
      plasma cells and eosinophilic in lamina propria of CRSsNP and inferior turbinate.
      Toluidine blue stain and immunohistochemical stain for tryptase were used to
      detect mast cell and its activation respectively in CRSsNP and control, and their
      corelations with tissue eosinophilia were analysed. RESULT: CRSsNP has increased
      total inflammatory cells, mononuclear cells and plasma cells but comparable
      eosinophilic and lamina propria glands compared with inferior turbinate. Mast
      cells corelated with activated mast cells, but there was no difference between
      CRSsNP and control for both of them and there were no corelation between mast
      cell and its activation with tissue eosinophilia. CONCLUSION: CRSsNP has more
      serious inflammation but no more mast cell and its activation and eosinophil
      compared with inferior turbinate, and there were no corelations between mast cell
      and its activation with eosinophil count which suggests that mast cell and
      eosinophilic inflammation mediated by it may not play an important role in the
      pathogenesis of CRSsNP.

PMID- 21171297
TI  - [The effect of specific immunotherapy on the regulation of Th1/Th2 cell ratio of
      the patients with allergic rhinitis in serum].
AB  - OBJECTIVE: To explore the effects of specific immunotherapy by the nasal spray
      and/or sublingual contain on the regulation the balance of serum Th1/Th2 cell
      ratio, and the expression of total IgE (tIgE) level in perennial allergic
      rhinitis patients. METHOD: Thirty-six cases of allergic rhinitis of perennial
      (PAR) patients with nasal specific immunotherapy (nasal spray group) were chosen
      as the object of study, 36 PAR patients with sublingual specific immunotherapy
      (sublingual group) were chosen for the efficacy comparison group, and 32 cases of
      healthy adults as control (normal control group). The levels of serum IL-2, IL-4,
      IL-8 and tIgE in PAR nasal spray group and sublingual group were examined by IRMA
      and double-antibody sandwich assay before and after the treatment of specific
      immunotherapy (SIT); The content of IFN-gamma was determined by enzyme-linked
      immunosorbent assay; The infiltration and changes of eosinophilic granulocyte
      were observed by the smear of nasal secretions. RESULT: In nasal spray group and
      sublingual group, the contents of serum Th1 cytokines IL-2 and IFN-gamma were
      reduced levels significantly, while the contents of Th2 cytokines IL-4, IL-8 and
      tIgE were significantly increased before the treatment of SIT. After the SIT to
      the maintenance dose, the levels of IL-2 and IFN-gamma in serum were
      significantly higher than that before treatment, while IL-4, IL-8 and tIgE
      content were significantly lower in AR patients (P < 0.01 or P < 0.05). The
      clinical efficacy of nasal spray group and sublingual group were 97.22% and
      94.44%, while the two groups was no statistical difference in efficacy (P >
      0.05). CONCLUSION: With the presence of Th1/Th2 cell ratio and cytokine
      imbalance, the AR patients manifested as Th2 cell function in accentuation. Nasal
      mucosa and/or sublingual in the local SIT can have changed no-balance Th1/Th2
      cell of by regulating the balance of serum Th1/Th2 cell ratio, the expression
      level of cytokine expression and the level of tIgE.

PMID- 21171298
TI  - [Different expression of histamine H4 receptor in nasal mucosa in allergic
      rhinitis patients].
AB  - OBJECTIVE: To observe expression and distribution of histamine H4 receptor in
      nasal mucosa in normal people and allergic rhinitis patients,and understand role
      of histamine H4 receptor in allergic rhinitis. METHOD: Select normal people and
      allergic rhinitis patients each 10, take the nasal mucosa, detect expression and
      distribution of histamine H4 receptor at proteins and transcription level
      respectively by immunohistochemical method and RT-PCR, and compared. RESULT:
      Histamine H4 receptor at proteins and transcription level were found in normal
      nasal mucosa (25 509 +/- 6 441, 0.42 +/- 0.08), increased significantly in nasal
      mucosa of allergic rhinitis patients (49 676 +/- 8 541, 0.69 +/- 0.11, P < 0.05),
      which in structural cells and immune cells. CONCLUSION: Histamine H4 receptors
      exist in normal nasal mucosa, its express significantly enhance, flew histamine
      H4 receptor may be mediated histamine in pathogenesis of allergic rhinitis ,who
      is one of the ligands of histamine.

PMID- 21171299
TI  - [The ocular optic fiber used in the endoscopic sinus surgery of
      dacryocystorhinostomy in the treatment of chronic dacryocystitis and recurrent
      dacryocystitis].
AB  - OBJECTIVE: To explore a method for locating the area of lacrimal sac in
      dacryocystorhinostomy under endoscopy. METHOD: Sixty-eight patients were
      performed dacryocystorhinostomy under endoscopy. Take light spot of ocular optic
      fiber as the lacrimal sac projection to the lateral wall of the nasal cavity
      position. RESULT: With the guiding of ocular optic fiber, lacrimal sac can be
      located accurately. The operating time of dacryocystorhinostomy under endoscopy
      was shortened significantly, and the operation procedure was simplified. All
      patients were followed up for 2 years, only 2 recurrent cases were found. The
      success rate reach to 97.06% (66/68). CONCLUSION: Ocular optical fiber used in
      locating the lacrimal sac in dacryocystorhinostomy under endoscopy is simple and
      feasible, and can be widely used.

PMID- 21171300
TI  - [The outcome of 256 cases of endoscopic sinus surgery].
AB  - OBJECTIVE: To evaluate the curative effect of endoscopic sinus surgery (ESS).
      METHOD: Two hundred and fifty-six cases with chronic sinusitis and nasal polyps,
      undergone ESS from 2001 to 2007 were analysed. There were 106 cases in type 1,
      134 cases in type 2 and 16 cases in type 3. Two hundred and forty-six cases
      undergone ESS with intranasal local anesthesia and potentialized anesthesia. Long
      time follow-up was performed at 9 to 42 months (mean = 15 months). RESULT: The
      results showed that cure rate was 78.3% for type 1, 66.4% for type 2 and 43.8%
      for type 3. There was significant difference in cure rate between type 1, type 2
      and type 3 (P < 0.01). Complication of ESS of 256 cases was 4.3%. CONCLUSION:
      There was higher efficacy and safety for relief of nasal polyps and for relief of
      chronic sinusitis with ESS. The difference of clinical type in nasal polyps and
      chronic sinusitis affected directly surgical result.

PMID- 21171301
TI  - [The investigation about the influence of deviated nasal septum on the
      adolescents learning quality].
AB  - OBJECTIVE: To investigate the incidence rate of deviated nasal septum (DNS) of
      the young men who are going to join the army, and of the students in key high
      schools in Jimo, and record their educational background, then analysis the
      influence of DNS on the youth's learning quality. METHOD: Random select 3085
      young men who are going to be recruited in 2006-2008, and 2628 students in 3 key
      high schools of Jimo. Investigate the two groups' incidence rate of DNS and make
      a correlative statistic analyses with their educational background. RESULT: There
      are 395 young men with DNS, which account 12.8% of the 3085 men, with the
      educational background of college degree and above account 3.0%; high school
      diploma 12.4%; junior secondary education 27.5%. One hundred and ninety-four
      students with DNS in key high schools, which account 7.4, and the subsequent
      entrance examination results shows, undergraduate students account 14.9%, junior
      college students and considerable education 32.5%, and graduates 52.6%.
      CONCLUSION: DNS can influence the learning quality of the adolescent. It is
      necessary to operate on those patients and improve the complaint symptom.

PMID- 21171302
TI  - [The role of intracellular Ca2+ release in olfactory signal transduction].
AB  - OBJECTIVE: To setup the real time monitor system of the concentration of free
      intracellular calcium ([Ca2+]i) of olfactory receptor neurons (ORNs) cultured
      from olfactory epithelium explant, and to analyze the role of several important
      components in olfactory signal transduction. METHOD: The [Ca2+]i of the cultured
      ORNs was determined by fluorescence microscopy using the fluorescent calcium
      indicator, Fura-2 AM, and calculated by means of dual-wavelength ratiometric
      method. Forskolin and IBMX were used to stimulate the cultured ORNs respectively.
      The source of corresponding [Ca2+]i elevation was studied by the depletion of
      extracellular or intracellular calcium. RESULT: The [Ca2+]i of silent ORNs was
      (58.5 +/- 12.8) nmol/L. Forskolin or IBMX stimulation led to reversible
      accumulation of [Ca2+]i in the ORNs. The [Ca2+]i change was abolished with the
      removal of extracellular Ca2+ and un-affected by treatment with thapsigargin.
      CONCLUSION: A system to visualize and quantify [Ca2+]i of the ORNs was
      established. [Ca2+]i of the ORNs was regulated by second messenger gated calcium
      channels.

PMID- 21171303
TI  - [Extended middle fossa approach in treatment of vestibular schwannoma--technique
      of surgery and postoperative complications].
AB  - INTRODUCTION: The main tumor of cerebellopontine angle are vestibular schwannoma
      (80-90%). According to National Institute of Health Consensus Development
      Conference the best treatment method is microsurgery. There are three principal
      surgical approaches: translabyrinthin, retrosigmoid and middle fossa. Only the
      latter two approaches provide the possibility of hearing preservation. AIM:
      Technique of surgery and postoperative morbidity after MFA. MATERIAL AND METHODS:
      39 patients (40 tumor) suffered from tumor of cerebellopontine angle, operated by
      using middle fossa approach in years 1998-2007. We evaluate hearing preservation
      and function of facial nerve and others postoperative morbidity. RESULTS: 22.5%
      of patients has hearing impairment and 32.5% has facial weakness. By individual
      cases we observed: CSF leak, meningitis, corneal ulceration, ischialgia, wound
      bleeding and venue thrombosis. 1/3 of patients suffered from headache and
      disequilibrium and 1/6 suffered from tinnitus. CONCLUSION: According to NIH
      middle fossa approach is one of three possible approaches in microsurgery of
      cerebellopontine angle tumors. There is possible total tumor removal with hearing
      preservation. Monitoring of facial and cochlear nerve during operation is
      recommended.

PMID- 21171304
TI  - [Correlation of auditory-verbal skills in patients with cochlear implants and
      their evaluation in positone emission tomography (PET)].
AB  - INTRODUCTION: An assumption was taken that in central nervous system (CNS) in
      patients above 15 years of age there are possible mechanisms of neuronal changes.
      Those changes allow for reconstruction or formation of natural activation pattern
      of appropriate brain structures responsible for auditory speech processing. AIM:
      The aim of the study was to observe if there are any dynamic functional changes
      in central nervous system and their correlation to the auditory-verbal skills of
      the patients. MATERIAL AND METHODS: Nine right-handed patients between 15 and 36
      years of age were examined, 6 females and 3 males. All of them were treated with
      cochlear implantation and are in frequent follow-up in the Department of
      Otolaryngology at the Medical University of Warsaw due to profound sensorineural
      hearing loss. In present study the patients were examined within 24 hours after
      the first fitting of the speech processor of the cochlear implant, and 1 and 2
      years subsequently. Combination of performed examinations consisted of: positone
      emission tomography of the brain, and audiological tests including speech
      assessment. In the group of patients 4 were postlingually deaf, and 5 were
      prelinqually deaf. RESULTS: Postlingually deaf patients achieved great
      improvement of hearing and speech understanding. In their first PET examination
      very intensive activation of visual cortex V1 and V2 (BA17 and 18) was observed.
      There was no significant activation in the dominant (left) hemisphere of the
      brain. In PET examination performed 1 and 2 years after the cochlear implantation
      no more V1 and V2 activation region was observed. Instead particular regions of
      the left hemisphere got activated. In prelingually deaf patients no significant
      changes in central nervous system were noticeable neither in PET nor in speech
      assessment, although their hearing possibilities improved. CONCLUSIONS: Positive
      correlation was observed between the level of speech understanding, linguistic
      skills and the activation of appropriate areas of the left hemisphere of the
      brain in postlingually deaf patients treated with cochlear implants. No such
      correlation was noted in prelingualy patients treated with the same method.

PMID- 21171305
TI  - [The effects of cochleostomy of hearing threshold in animal experiment].
AB  - INTRODUCTION: To assess an effect of cochleostomy on hearing threshold in guinea
      pigs. MATERIAL AND METHODS: The authors performed animal experiments using five 3
      month-old guinea pigs. Before experiment hearing threshold were evaluated.
      Surgery involved access to the temporal bone by a post-auricular incision. After
      a wide opening of the bulla cochleostomy was created (10,000 turn/min, diamond
      bur of 0.8 mm diameter). Hearing threshold was identified on the basis of
      presence of wave V in auditory brainstem responses (ABR) for click and frequency
      specific stimulation. Also morphology and latency changes for wave V for this
      stimulation was assessed. Hearing status was evaluated before, just after and 1-,
      2-, and 4-weeks after surgery. For surgical procedure and ABR examination all
      animals were anesthetized with an intramuscular injection of ketamine (50 mg/kg)
      mixed with xylazine (9 mg/kg) in the supplemental doses. After surgery the animal
      was treated by antibioticoterapy for 3 days--Enrofloksacyna 0.3 ml subcutaneouly
      and analgesic--Tolfedine 0.05 mg in second day. RESULTS: Four week observation of
      ABR morphology and hearing thresholds for click and frequency-specific
      stimulation of 100 dB SPL intensity showed only temporary changes confirming that
      cochleostomy did not affect cochlear function. CONCLUSIONS: The correctly
      performed cochleostomy in guinea pigs did not affect persistently the cochlear
      function indicating that such an option of CI electrode insertion in patients is
      safe.

PMID- 21171306
TI  - [Auditory skills in multi-handicapped children with cochlear implants].
AB  - AIM: The study aimed to assess the auditory skills in multi-handicapped children
      with cochlear implants. MATERIAL AND METHODS: The study assessed 34 children, who
      were implanted due to the bilateral profound sensorineural hearing loss. Apart
      from the hearing loss, all of the subjects suffered from additional impairments
      (mild motor disabilities, cerebral palsy, cognitive disability, specific learning
      disability, behavioral disorders, sight impairment), 29 (85.29%) from more than
      one. Cochlear implantation took place in the Department of Otolaryngology at the
      Medical University of Warsaw in Poland. The age at implantation ranged from 1.3
      to 7.5 years old (mean 3.2 years, SD 1.64). The retrospective review of medical
      charts, audiology and speech pathology records was based on Champions profile
      with evaluation at 6, 12, 18-24 months, and 3 years after implantation. When a
      patient had been referred for developmental evaluation by psychologist, this
      source of information was also used. RESULTS: All of the subjects suffered from
      additional impairments, and most of them presented more than one additional
      disability. Individually and as a group, these patients respond well to cochlear
      implantation. The study population showed improvement in communication code in 31
      patients (91.18%), and no improvement in 3 patients (two of them had 6 months
      follow up and one 12 months follow-up). Also progress in auditory skills was
      noted in the study population, which was measured as the awareness in
      environmental sounds--Categories of Auditory Performance (CAP). CONCLUSIONS:
      Multi-handicapped children receive benefit from cochlear implantation. The rate
      of this improvement is slow but offers better quality of life due to better
      auditory-communication skills, better self-independence and social integration.
      The results of implantation in presented group of patients is encouraging.

PMID- 21171307
TI  - [Analysis of morphology of auditory brainstem with idiopathic peripheral facial
      nerve paresis responses in patients].
AB  - INTRODUCTION: Idiopathic facial nerve paresis still remains a challenge for
      laryngologists and neurologists. The etiology of idiopathic peripheral facial
      nerve paresis has not been explained so far. There is a group of patients that
      complain about coexisting hearing abnormalities. AIM: Analysis of audiological
      abnormalities in patients with idiopathic peripheral facial nerve paresis on the
      basis of pure tone audiometry and auditory brainstem responses. MATERIAL AND
      METHODS: The retrospective analysis of 35 patients, aged under 40 years, with
      idiopathic peripheral facial nerve paresis hospitalised in Department of
      Otolaryngology of Warsaw Medical University-Poland (2004-2009). Control group
      consisted of age-matched, 23 healthy subjects. Each patient underwent audiometric
      evaluation that included pure tone audiometry and auditory brainstem responses.
      Statistical analysis was performed with Student's t-test. RESULTS: In the
      analysed group of 35 patients (17 male + 18 female), age ranged 13-40 years (mean
      26.7 +/- 7.1) significantly prolonged latencies of wave III and V and III-V and I
      V intervals in comparison with control group where observed (p < 0.05). We found
      also that 48.6% patients with idiopathic peripheral facial nerve paresis had high
      frequency hearing loss. CONCLUSIONS: The auditory brainstem responses in this
      study showed an association between retrocochlear pathology of the auditory
      system and idiopathic peripheral facial nerve paresis. Further investigations are
      necessary to estimate the etiopathology of these coexisting abnormalities.

PMID- 21171308
TI  - [The use of VHIT (videonystagmography head impulse test) in the diagnostics of
      semicircular canal injuries].
AB  - INTRODUCTION: The aim of that work was to evaluate the usefulness of VHIT
      (Videonystagmography Head Impulse Test) in the diagnostics of injuries to the
      semicircular canals. MATERIAL AND METHODS: The tests covered 58 patients aged 20
      27, including 34 women and 24 men. Any deviations within the vestibular organs
      was excluded in the interview, otorhinolaryngological examination and full
      videonystagmographic test. The tests checked functions of the semicircular canals
      in the following way: in a sitting position and the head leaned forward at 30
      degrees the patient was looking at a motionless point while quick movements to
      the left or right were performed to stimulate a particular lateral semicircular
      canal. When the vertical semicircular canals were tested the head was inclined
      laterally to the right side at 45 degrees. Then similar movements were performed
      forwards (stimulation of the left anterior semicircular canal) and backwards
      (stimulation of the right posterior semicircular canal). When the head was leaned
      laterally to the left at 45 degrees the right or left anterior semicircular canal
      was stimulated respectively. Functions of the canal were determined on the basis
      of gain (%). RESULTS OF THE TESTS: In 58 patients the gain value for particular
      semicircular canals was normal, and the mean values presented as follows: the
      lateral semicircular canal: 11.9% +/- 10.2, the anterior semicircular canal:
      17.5% +/- 11.6 and the posterior semicircular canal: 19.2% +/- 13.5, whereas on
      the left side: 10.3% +/- 7.9, 18.1% +/- 11.1, 15.1% +/- 12.3 respectively. In one
      man the gain value for the right posterior semicircular canal was found
      significantly above the standard value--71%. CONCLUSION: VHIT showed much more
      sensitive than a full videonystagmographic test.

PMID- 21171309
TI  - [Radiologic picture of maxillary sinus aspergilloma].
AB  - INTRODUCTION: Mycotic infection of paranasal sinus could be the etiological
      factor of chronic sinusitis. The increase in number of fungal sinusitis cases
      have been reported recently among nonimmunocompromised patient after endodontic
      treatment of maxillary teeth. Nonspecific clinical signs and incorrect radiologic
      pictures interpretation as well as loss of therapeutic standards seems to be the
      cause of false negative diagnosis and difficulties in treatment of fungal
      sinusitis. AIM OF THE STUDY: Clinical and radiological picture of maxillary sinus
      aspergillosis was described in this paper. MATERIAL AND METHODS: In the period of
      2006-2009 in the Department of Maxillo-Facial Surgery 19 patient with fungal
      maxillary sinusitis was treated. The endodontic treatment of maxillary teeth of
      the related side was performed previously in 80% examined cases. In 2 cases there
      were immunocompromised patients with immunosuppressive treatment. In 16 cases
      patients were referred to our Department due to metallic foreign body of the
      maxillary sinus. Routine diagnostic radiological imaging was performed in each
      case: paranasal sinus view--Water's view and panoramic radiograph
      (orthopantomograph). In 4 cases imaging was extended with computer tomography
      (CT) visualization. The surgical treatment was performed in each case. The final
      diagnosis was puted on histopathological examination and fungal culture. RESULTS:
      In 16 cases of analysed group histopathological examination and fungal culture
      revealed aspergilosis. In 2 cases fungal culture was negative, but histopathology
      slices confirm presence of hyphae of Aspergillus. In 1 case the root canal sealer
      was found in the maxillary sinus. In none case invasive form of aspergillosis was
      confirmed. In all cases Water's view of paranasal sinuses and ortopantomograph
      showed partially or totally clouded sinus with well-defined, single or multifocal
      radiopaque object similar to metallic foreign body. Characteristic finding in CT
      imaging was well-defined radiodence concretions that have been attributed to
      calcium deposits in inflammatory changed mucosa, that might suggest "foreign
      body" picture. In 1 to 3 years follow-up control there was a recurrence of
      symptoms in one case. CONCLUSIONS: Foreign body of maxillary sinus have to be
      differentiated with aspergilosis. Metallic "foreign body" view in maxillary sinus
      seems to be characteristic sign of aspergillosis. The most often form of
      maxillary sinus aspergilosis is aspergilloma.

PMID- 21171310
TI  - [Draf III procedures: the ENT Department, Medical University of Warsaw
      experience].
AB  - During last decades Draf III procedure gained popularity in treatment of
      different pathologies of the frontal sinus such as chronic sinusitis or benign
      tumors. We present a series of 10 patients treated with this procedure from a 2
      year-period. Indications included: chronic rhinosinusitis--four patients, frontal
      sinus mucocele--four patients (one with destruction of the posterior table),
      osteoma--one patient (stage 3 according to Kennedy's grading system), and
      inverted papilloma--one patient (Krouse T3 lesion). Observation period ranged
      from 4 months to 2 years. RESULTS: There were no early complications. Gradual
      narrowing of the created ostium was observed in all of the patients. This led to
      total obstruction in two, and stenosis (not allowing for passing with 4 mm
      endoscope) in another two patients. The patient after inverted papilloma removal
      showed no recurrence in 11 months follow-up. CONCLUSION: Draf III procedure is
      alternative for external approach that can be used for treatment of chronic
      rhinosinusitis and benign frontal sinus tumors of different size.

PMID- 21171311
TI  - [Recurrence of cancer of the paranasal sinuses after primary treatment--analysis
      of conditions and results of salvage treatment].
AB  - THE AIM OF THIS STUDY: is to demonstrate epidemiological and clinical parameters
      of the group of patients with sinonasal malignancies and to analyze its impact on
      development of recurrences after primary surgical treatment conducted in Head and
      Neck Surgery Department of Holly Cross Cancer Center Kielce during 7-years period
      2001-2007. The retrospective analysis of the group of 42 patients with sinonasal
      malignancies was made, based on medical record and outpatient follow-up,
      considering: age, sex, primary focus, histological outcome, local and clinical
      stage and methods of the therapy. In the group of patients with at least 3-years
      period of follow-up (n=42) the dependence the rate of oncological failures such
      as local recurrence, nodal metastases, distant metastases or the second primary
      focus on clinical and epidemiological factors was analyzed. The probability of
      survival rate was also estimated. The studied group consists of 42 patients (27M,
      15K, M:K = 1.8:1). Age ranged from 28 to 87. The most common localization was
      maxillary sinus--59.5%. Patients with high local (T3, T4) and clinical (III, IV)
      stage constitute 77.5% of the studied group. In 66.7% cases the radiation therapy
      had to follow the surgery. In the group of 42 patients with at least 3-years
      period of follow-up the oncological failure appeared in 17 cases (40.5%): local
      recurrence (8), nodal metastases (7), distant metastases (1) and all of them in 1
      case. The treatment was performed through: local recurrence (surgery in 2 cases,
      CHTH--3, symptomatic treatment--3), nodal metastases (RND--3, SND--4,
      supplementary radiotherapy--7), distant metastases--CHTH--2 cases. Thanks to
      these procedures the 5-year survival rate is 23.1% and the 3-year survival rate
      is 29.4%. CONCLUSIONS: (1) The oncological failure after primary surgical
      treatment in the group of patients with sinonasal malignancies developed in 40.5%
      cases, mainly as local recurrence or nodal metastases. (2) Primary localization
      and sex have no impact on the rate of the recurrence. (3) The oncological
      failures significantly more often relate to young patients with high local,
      clinical stage and low grade of malignancies. (4) The recurrence after primary
      surgical treatment in the group of patients with sinonasal malignancies
      substantially reduces 3- and 5-year survival rate (29.4%; 23.1%) compared with
      the entire studied group--54.8%; 40.0%.

PMID- 21171312
TI  - [Management of recurrent pleomorphic adenoma of the parotid gland: analysis of
      the material of Otolaryngology Department, Medical University of Warsaw between
      1998 and 2008].
AB  - OBJECTIVES: Treatment of patients with recurrent pleomorphic adenoma of the
      parotid gland is a challenge for a surgeon due to frequent problems with complete
      resection of all tumour foci while preserving continuity and function of the
      facial nerve. The aim of this study was to evaluate the clinical presentation and
      treatment results of patients with recurrent pleomorphic adenoma of the parotid
      gland. MATERIALS AND METHODS: The medical records of 35 patients (25 women and 10
      men) operated on (44 operations) for recurrent pleomorphic adenoma between the
      years 1988 and 2008 at the Otolaryngology Department, Medical University of
      Warsaw, were reviewed. These patients accounted for 8.9% of all patients treated
      for pleomorphic adenoma of the parotid gland (N=395). A retrospective analysis
      was performed to examine clinical features, surgical technique and facial nerve
      management. RESULTS: All patients had palpable, nontender mass or masses in a
      parotid bed after 1 to 5 previous operations. Multifocal recurrences were present
      in 79.5% of cases. Median interval between initial treatment and commencement of
      recurrences was 6.1 (0.25-29) years. Patients with more than one recurrence were
      younger than patients who had only one. Malignant transformation of recurrent
      pleomorphic adenoma was observed in two patients (5.7%). Postoperative facial
      nerve paresis occurred in 15 cases. In two additional cases eradication of
      recurrent tumour required the facial nerve resection and reconstruction.
      CONCLUSIONS: Recurrent pleomorphic adenoma occurs more often in younger patients
      and women. The risk of the facial nerve injury increases with each successive
      operation. Surgical treatment should be individualized, taking into consideration
      the extent of the previous surgery and the type of recurrence.

PMID- 21171313
TI  - [Melanoma of the head and neck region in material of Department of Oncological
      and Reconstructive Surgery in Center of Oncology IMSC in Gliwice].
AB  - INTRODUCTION: About 25% of melanomas are localized in head and neck skin, and
      this particular localization is most difficult to treat, and the prognosis is
      less favorable. The depth of melanoma infiltration (Clark and Breslau grade) into
      the skin is the main factor of local advancement of the disease. Surgical
      treatment is an essential therapeutic modality in patients with melanoma. AIM:
      The aim of this study was to evaluate results of our surgical treatment of
      melanomas in head and neck localisation, treated from 1997 to 2007 in Department
      of Oncological and Reconstructive Surgery in Center of Oncology IMSC in Gliwice.
      MATERIAL: We analysed group of 47 patients (aged 26 to 75 years, mean 49),
      treated by surgical excision of malignant melanoma in the head and neck region.
      Most of the patiens required to use free flaps or skin graft technique to close
      posexcisional defect, on basis of clinical considerations. RESULTS: The 5-year
      total survival for all patients was 62% and were dependent on depht of melanoma
      infiltration and regional lymph node metastasis. The significant prognostic
      factors were: localization of primary focus, local progression of disease, free
      microscopical excision margins sex and age. CONCLUSIONS: Prognosis in the
      patients with melanoma of the head and neck is unreliable and dependent on local
      advancement of disease and localization of primary focus. Surgical treatment is
      an essential therapeutic modality in patients with melanoma. Adiuvant
      radiotherapy after surgical treatment of melanoma of the head and neck is
      intended for the patiens with high risk of local or regional recurence of
      disease.

PMID- 21171314
TI  - [Accelerated postoperative radiotherapy in patients with advanced larynx cancer].
AB  - AIM: The aim of study was test efficacy of accelerated postoperative radiotherapy
      -concomitant boost in patients with advanced larynx cancer. METHODS AND
      MATERIALS: The prospective study included 112 patients with advanced larynx
      cancer after radical surgical treatment. Patients had postoperative radiation
      therapy, conventional (C) or accelerated (CB). RESULTS: The 3-year overall
      survival in CB was 59%, in C--58% (p = 0.2), 3-year locoregional control in CB-
      83%, in C--75% (p = 0.01), the 3-year disease free survival was in CB--72%, C-
      66% (p = 0.1). CONCLUSION: Concomitant boost postoperative radiation therapy did
      not improve overall survival, loco-regional control, disease free survival.
      Patients with close surgical margins, longer interval between surgery and
      radiation, high level of hemoglobin, T4 had benefit from accelerated
      radiotherapy.

PMID- 21171315
TI  - [Paragangliomas of the neck--a 10-year experience of the Department of
      Otolaryngology of Warsaw Medical University].
AB  - Paragangliomas are rare neoplasms of neurological origin and account for 0.012%
      of all tumors. Only 10% of them have extraadrenal localization. Head and neck
      paragangliomas account for 0.33% neoplasms of that localization. Typically
      paragangliomas are benign tumors, but even 19% cases may have malignant
      potential. On the neck they are located typically closely to carotid artery
      bifurcation, jugular bulb and along the course of vagus nerve. Laryngeal
      localization is very rare. Nonspecific manifestation and wide spectrum of
      symptoms cause difficulty in diagnosis of paragangliomas. AIM: Presentation of
      the diagnostic process, performed treatment and obtained results of neck
      paragangliomas in the material of the Department of Otolaryngology of Warsaw
      Medical University in years 2001-2010. MATERIAL AND METHODS: There was performed
      retrospective analysis, based on the medical documentation of 14 patients with
      neck paragangliomas (9 women and 5 men), age range 25-62 years, hospitalized in
      the Department of Otolaryngology of Warsaw Medical University during the last 10
      years. The date from the history, physical examination, radiological evaluation
      and the method of performed treatment and post-treatment complications were
      studied. RESULTS: Out of 14 patients with neck paragangliomas, there were 9 cases
      of isolated tumors and 5 cases of synchronic, multicentric neoplasms. The most
      common and single symptom was nonspecific neck mass. Doppler ultrasonography was
      adequate diagnostic tool in carotid artery paragangliomas. To diagnose
      mulicentric paraganglioma, vagal or laryngeal paraganglioma more thorough
      radiological examination was necessary, including computed tomography, magnetic
      resonance and angiography. All patients had performed surgical treatment. There
      were observed very good results in patients with isolated paragangiomas of
      carotid artery or larynx. Surgical management of multicentric and vagal
      paragangliomas was exposed to higher risk of cranial nerve paresis. CONCLUSIONS:
      (1) Paragangliomas are rare tumors of nonspecific clinical manifestation, making
      the early diagnosis very difficult. (2) Precise radiological evaluation is
      necessary taking into consideration quite high incidence of multicentric
      paragangliomas. (3) There is higher risk of cranial nerve paresis after surgical
      treatment of multicentric paragangliomas, neoplasms larger then 5 centimeters in
      diameter and vagal paragangliomas then in isolated carotid artery paragangliomas.

PMID- 21171316
TI  - [Management of recurrent sinonasal inverted papilloma in the experience of ENT
      Department Medical University of Warsaw].
AB  - INTRODUCTION: Inverted papilloma is benign epidermal neoplasm of not recognized
      etiology. The lesion is estimated to represent 0.5-4% of sinonasal tumors.
      Generally inverted papilloma is unilateral, arises from the lateral nasal wall
      and characterizes with local destruction and rapid growth. The tumor can possibly
      undergo malignant transformation. The treatment of choice is surgery, recently
      endoscopic approach is considered to be superior to the open approach. THE AIM OF
      STUDY: was evaluation of recurrent inverted papilloma treatment results in the
      experience of Otolaryngology Department, Medical University of Warsaw, from 1982
      to 2009. MATERIAL: The group of 124 patient (66 men and 58 women) aged from 26 to
      79 with inverted papilloma operated between 1982 and 2009 were enrolled in the
      study. Follow up was from 6 months to 27 years. RESULTS: Most common primary
      localization of the tumor was combined lateral nasal wall and maxillary sinus
      (42%). In 37% the lesion involved unilaterally the lateral nasal wall, maxillary
      sinus and ethmoid sinuses, rarely it was localized only in the lateral nasal wall
      (16.1%) and exclusively in the nasal septum (4.8%). All the patients were treated
      surgically, 46% of patients underwent endoscopic procedure, 37.1% lateral
      rhinotomy, 15% Denker rhinotomy and 1.6% midfacial degloving. Recurrence was
      observed in 15.3% including 57.9% after endoscopic surgery, 26% after Denker
      operation and 15.8% after lateral rhinotomy. Malignant transformation was
      observed in 5 patient (4%). All the patients with recurrent inverted papilloma
      were treated surgically, 5.3% of patient underwent midfacial degloving, 5.3%
      Caldwell-Luc operation, 10.5% endoscopic procedure, 26.3% Denker operation and
      52.6% lateral rhinotomy. CONCLUSIONS: 1. Endonasal and open approach should be
      considered in the surgical treatment of recurrent inverted papilloma. 2.
      Endoscopic approach is preferred in the recent years but qualification for each
      method should depend on lesion localization, extent and volume. 3. Regular follow
      up enables early recurrence diagnosis and treatment.

PMID- 21171317
TI  - [Round window's movability measurements with helping of LDV in evaluation of
      ossicular chain functioning].
AB  - Round window's movability measurements with helping of LDV in evaluation of
      ossicular chain functioning. AIM OF STUDY: Quantitive evaluation of round window
      movability in normal conditions and after malleus stapes assembly reconstruction
      were aims of the study. METHODS AND MATERIALS: In the experiment there were taken
      10 non-frozen temporal bones harvested within 48 hours. Temporal bones specimens
      were prepared like in closed technique with antromastoidectomy and large
      posterior tympanotomy. Hearing system before and after MSA reconstruction were
      evaluated by measurement of round window movement. Measurements were performed at
      four frequencies: 1000 Hz, 2000 Hz, 4000 Hz, 8000 Hz. RESULTS: In the normal
      ossicular chain the biggest movability were stated at frequency of 1 kHz. After
      reconstruction at all frequencies measurements were significantly worse. In
      reconstructed ears the highest movabilities were stated at frequencies 2000 Hz
      and 4000 Hz. CONCLUSIONS: Round window movability could be measured by Laser
      Doppler Vibrometry in posterior tympanotomy approach. Before reconstruction the
      biggest movability were evaluated at 1000 Hz and after MSA at 2000 Hz

PMID- 21171318
TI  - [Lateral petrosectomy in pathology of the temporal bone].
AB  - INTRODUCTION: Certain problems in ear surgery are caused by temporal bone
      cholestetoma and chronic otitis media complicated by deafness, facial nerve
      dysfunction, vertigo or meningcephalocele. Lateral petrosectomy offers
      possibility of radical treatment and prevention of temporal bone destruction and
      following complications. AIM OF STUDY: It is an analysis of indications for
      lateral petrosectomy and it's results as a treatment of otitis media and temporal
      bone cholesteatoma. The possibility of synchronous cochlear implantation is
      noted. MATERIAL: Retrospective analysis of 62 patients after lateral
      petrosectomy, operated in the Department of Otolaryngology at the Medical
      University of Warsaw in 2001-2009. The group consisted of thirty one men and
      thirty one women. RESULTS: Thirty two patients suffered from chronic granuloma or
      chronic choleateatoma otitis media or temporal bone cholesteatoma. Seventeen
      patients suffered from deafness prior surgery. Cochlear implantation was possible
      in five patients: two of them after cranium fracture, two with deafness caused by
      chronic otitis media and one with deafness caused by osteoradionecrosis.
      Intraoperative CSF leak was observed of eight patients. In one case lateral
      perosectomy was used as a treatment of CSF leak after removal of cerebellopontine
      tumor. There was no evidence of CSF leak after surgery. Facial nerve dysfunction
      was observed in fifteen cases. CONCLUSIONS: Lateral petrosectomy offers
      possibility of radical treatment in same patients with chronic otorrhea. The
      total removal of cholesteatoma prevents intracranial and intratemporal
      complications in case of chronic otitis media. Patients after lateral
      petrosectomy require systematic ENT and radiological (CT, NMR) examination.

PMID- 21171319
TI  - [Effects of Chinese herbs on enkephalin mRNA and prodynorphin mRNA gene
      expression in rat hippocampus with chronic immobilization stress].
AB  - AIM: To investigate the changes of enkephalin mRNA and prodynorphin mRNA gene
      expression in rat brain regions with chronic immobilization stress and the
      influence of Chinese herbs. METHODS: We copied the rat model of chronic
      immobilization stress (3 h daily , repeated 7 d or 21 d), and primers of
      enkephalin or prodynorphin were respectively added for RT-PCR reaction (BETA
      actin as inner contrast). Gel image analysis system was used to scan and analyze
      and odds of optical density of target gene and inner contrast strip were taken as
      quasi-quantified data. RESULTS: Prodynorphin mRNA expression in hippocampus
      markedly increased in 7 d group (P < 0.01), while enkephalin mRNA prodynorphin
      mRNA expression in hippocampus markedly increased in 21 d group (P < 0.01). All
      three recipes were able to decrease the gene expression of prodynorphin mRNA (P <
      0.01), and xiaoyao powder as well as sijunzi soup were able to decrease the gene
      expression of enkephalin mRNA (P < 0.01). CONCLUSION: The effects of xiaoyao
      powder on the above two gene expression was better than jinkuishenqi pill.

PMID- 21171320
TI  - [The role of monophosphoryl lipid A in protection against ischemia/reperfusion
      injury of rat myocardia].

PMID- 21171321
TI  - [Relation between GLu-R and the protective effect of hypothermia on oxygen and
      glucose deprivation injury in hippocampal slice or rat].
AB  - AIM: To investigate the relation between Glu-R and the protective effect of
      hypothermia on oxygen and glucose deprivation (OGD) injury in hippocampal slices
      of rat. METHODS: (1) We had established OGD injury model in rat hippocampal
      slices. The changes of orthodromic population spike(OPS) during OGD and after
      administration of hypothermia (32 degrees C, 25 degrees C) were observed. (2) We
      had established Glu excitatory toxicity injury model in rat hippocampal slices.
      The changes of OPS after exposure to Glu and the effect of hypothermia (32
      degrees C, 25 degrees C) against the Glu excitatory toxicity injury were
      observed. The non-NMDA receptor-mediated excitatory postsynaptic potentials
      (EPSP) in the CA1 area were recorded via adding the GABA-R specific agonists
      bicuculline (BMI) and NMDAR agonists D-(-)-2-Amino-5-phosphonopentanoic Acid
      (AP5) in normal artificial cerebrospinal fluid (nACSF), the NMDA receptor
      mediated EPSP were recorded via adding the BMI and non-NMDA-R agonists 6,7
      Dinitroquinoxaline-2, 3(1H,4H)-dione(CNQX) in nACSF. The variety of the changes
      of OPS during OGD14min in nACSF groups and added BMI compounded AP5 or BMI
      compounded CNQX ACSF groups were observed after administration of 25 degrees C
      hypothermia 28 min. (3) The changes of ultrastructure of CA1 area after OGD 1 h
      and the effect of hypothermia (25 degrees C) on it were observed. RESULTS: (1)
      OPS reduced and abolished quickly during OGD14min, and the recovery amplitude of
      OPS was very low after reoxygenation/glucose 1 h. While the time of OPS
      abolishing significantly elongated and the recovery of OPS was higher in
      hypothermia (32 degrees, 25 degrees C) groups. The effect in groups 25 degrees C
      was more significant than those in groups 32 degrees C. (2) In control groups,
      Glu (2 mmol/L, 14 min) decreased the amplitude of OPS, after the end of Glu
      exposure the recovery amplitude of OPS was very low. After administration of
      hypothermia (32 degrees C, 25 degrees C), the recovery amplitude and rate of OPS
      were significantly higher than those in the control groups, while the antagonism
      on Glu excitatory toxicity injury in H 25 degrees C was more significant than
      those in H 32 degrees C. The changes of OPS during OGD 14 min were no distinct
      difference in nACSF groups and added BMI (50 micromol/L) compounded AP5(20
      micromol/L) or BMI (50 micromol/L) compounded CNQX (100 micromol/L) ACSF groups.
      The protection of hypothermia (25 degrees C) could not be cancelled by added AP5
      compounded BMI or BMI compounded CNQX in nACSF. (3) After OGD (14 min) 1 h, the
      nuclear membrane of pyramidal cells in CA1 area was irregular, nucleus were
      homogenized, the organelle in the cytoplasm was degenerate, even more to necrosis
      or loss, mitochondrion swelled, ridge was vacuoles. In H 25 degrees C the nuclear
      membrane was regular, mitochondrion swelled only lightly. Small chromatin
      gathered to edge. CONCLUSION: Hypothermia shows the protective effects of against
      OGD injury in hippocampal slices. The mechanism is related to the antagonism of
      Glu excitor toxicity and maintenance the ATP level in cells, and the antagonism
      perhaps is mediated by NMDA-R and non-NMDA-R.

PMID- 21171322
TI  - [Effect of platelet-activating factor on long-term potentiation in rat
      hippocampal slices].
AB  - AIM: To explore the effect of platelet-activating factor on long-term
      potentiation in the CA1 region of rat hippocampal slices. METHODS: We recorded
      the excitatory postsynaptic potentials (EPSPs) and investigated effect of long
      term potentiation by PAF in rat hippocampus in vitro. RESULTS: Low doses (1
      micromol/L ) of PAF could induce LTP, while higher doses (10-50 micromol/L) of
      PAF could inhibit induction of LTP. But it couldn't inhibit the LTP induced by
      subsequent high frequency stimulation and the EPSP of basal. GB of PAF receptor
      antagonists could prevent the LTP induced by low doses of PAF, and could't
      inhibit the LTP induced by HFS. CONCLUSION: Higher doses of PAF is an HIV-1
      induced neurotoxin, it may contribute to the HAD pathogenesis by inhibition of
      LTP.

PMID- 21171323
TI  - [Study of the genes expression of SCD-2 and B-FABP in the mice brain of exercise
      induced fatigue by genechip cDNA microarray].
AB  - AIM: By genechip cDNA microarray, the genes expressions of Stearoyl-coenzyme A
      desaturase (Scd-2) and brain fatty acid-binding protein (B-FABP) were studied in
      the central nervous system (CNS) of the mice to discuss the mechanism of exercise
      induced fatigue. METHODS: Building the model of fatigued animal and using the
      genechip cDNA microarray, the genes expressions were analyzed between the control
      group and fatigue group mice. RESULTS: The genes expression of Scd-2 and B-FABP
      were obvious different in the brain of fatigued group mice than of control group.
      CONCLUSION: Exercise-induced nerve center fatigue is correlated with genes
      expressions of lipid metabolism.

PMID- 21171324
TI  - [Effect of the Ca2+ -activated K+ channel in veratridine-induced cortex neurons
      damage].
AB  - AIM: To observe the effects of Ca2+ -activated K+ channel of primary cultured
      fetal SD rat cortex neurons in the veratridine triggered neuronal damage.
      METHODS: The patch clamp technique of cell-attach and inside-out mode for these
      two kinds of single channel recordings were used. RESULTS: Extracellular
      veratridine activated the Kca. In Ca2+ bath solution of cell-attach mode, Vp + 30
      mV, when the concentration (micromol/L) of veratridine were 15,25,50 and 75, the
      open probabilities of the channel were 0.014 +/- 0.003, 0.085 +/- 0.010, 0.132 +/
      0.016 and 0.059 +/- 0.006 (P < 0.01) respectively. It appeared concentration
      dependent within 50 micromol/L veratridine. In Ca2+ free bath solution of cell
      attach mode, Vp = +50 mV, when the concentration (micromol/L) of veratridine were
      15, 40,60 and 100, the open probabilities of the channel were 0.014 +/- 0.010,
      0.113 +/- 0.006, 0.141 +/- 0.004 and 0.295 +/- 0.009 (P < 0.05) respectively. In
      the 6 cases of inside-out mode patch clamp, Vp = +40 mV, when the concentration
      of veratridine were 0, 25 micromol/L and 50 micromol/L, the open probabilities of
      the channel were 0.011 +/- 0.008, 0.010 +/- 0.010 and 0.012 +/- 0.007 (P > 0.05)
      respectively. There were no significant difference on open probabilities, average
      open/close times and amplitudes at different intracellular veratridine
      concentration. CONCLUSION: Veratridine can affect the activation of the Kca
      channel through regulating the concentration of cytoplasmic free Ca2+. The
      opening of Kca activated by increase of intracellular Ca2+ during the early stage
      of anoxia may be a protection reaction of ischemic neurons.

PMID- 21171325
TI  - [Effects of ginseng stem and leave saponin on prolactin and menstrual cycle of
      experimental hyperprolactinemia rats].

PMID- 21171326
TI  - [Effect of intracerebroventricular injection of adrenomedullin on
      catecholaminergic neurons and expression of c-fos in the rat brain nuclei
      involved in cardiovascular regulation].
AB  - AIM AND METHODS: Using double immunohistochemical method for Fos and tyrosine
      hydroxylase(TH) to examine the effects of intracerebroventricular (icv)
      administration of adrenomedullin (AM) on catecholaminergic neurons and the
      expression of c-fos gene in rat brain nuclei involved in cardiovascular
      regulation in order to define whether the effects of central administration of
      adrenomedullin (AM) were induced by activating the catecholaminergic neurons.
      RESULTS: (1) Following icy administration of AM (3 nmol/kg), Fos-like
      immunoreactivity neurons were markedly increased in several brain areas of the
      rat, including the brainstem, the hypothalamus and the forebrain. (2) Following
      icy administration of AM (3 nmol/kg), double-labeled neurons for Fos and TH
      increased significantly in the area postrema (AP), the nucleus of the solitary
      tract (NTS), the nucleus paragigantocellularis lateralis (PGL) and the locus
      coeruleus (LC). (3) Pretreatment with calcitonin gene-related peptide receptor
      antagonism CGRP (8-37) (30 nmol/kg) significantly reduced the action of AM (3
      nmol/kg) in the brain. CONCLUSION: AM activates the nuclei involved in
      cardiovascular regulation in the forebrain, the hypothalamus and the brainstem,
      and that the central actions of AM are induced by activating the
      catecholaminergic neurons of brainstem nuclei involved in cardiovascular
      regulation. CGRP receptor can mediate the effects of AM in brain.

PMID- 21171327
TI  - [Effect of lactic acid on the survival rate of cultured rat cortex neurons in
      vitro].
AB  - AIM: To prob the effect of lactic acid on the survival rate of cultured rat
      cortex neurons. METHODS: Neurons in primary culture were divided into two parts:
      (1) Neurons were cultured in physical medium, which was rendered acidotic by
      addition of lactic acid in rising concentrations. 0 mmol/L, 5 mmol/L, 10 mmol/L,
      20 mmol/L, pH range were 7.35, 7.15, 6.95, 6.00. (2) The cells were cultured in
      physical medium in the presence of lactic acid at increasing concentrations,
      respectively including lactate 0 mmol/L, 5 mmol/L, 10 mmol/L, 20 mmol/L. They
      were regulated to maintain pH 7.35. MTT was used to detect the neurons survival
      rate. RESULTS: Neurons survival rate significantly decreased with the pH decrease
      compared with the group pH 7.35. Different lactate concentrations can also reduce
      the neurons survival rate apparently compared with the group included no lactate.
      The survival rate of groups pH 7.15 and pH 6.95 were lower than the group in
      which the lactate concentration was 5 mmol/L and 10 mmol/L. CONCLUSION: It has
      close relation between pH decrease induced by lactate and neurons survival rate.
      Lactate can also exert neuron toxicity independently without pH decrease.

PMID- 21171328
TI  - [The effects of simulated hypoxia on the development of hypothalamic CRF and AVP
      neurons in postnatal rats].
AB  - AIM: To investigate the influence of hypoxia on postnatal developing pattern of
      hypothalamic corticotropin releasing factor(CRF) and arginine vasopressin (AVP)
      in male and female neonatal rats. METHODS: The hypoxia was simulated in hypobaric
      cabin. The content of AVP and CRF was assayed by RIA method. RESULTS: It was
      showed the female rats had the similar developing process with male rats, either
      at 2300 m or at 5000 m altitude. When they developed at simulated 5000 m
      altitude, the content of their hypothalamic CRF was lower than that of control
      rats on postnatal day 21, while the content of AVP was higher than control on day
      21 and 28. CONCLUSION: Maybe the difference of the function between hypothalamic
      CRF and AVP or/and the incoherence of their developing stage contribute to their
      particular developing pattern at 5000 m altitude.

PMID- 21171329
TI  - [Cardiovascular response caused by intracerebroventricular microinjection of
      interleukin-2].
AB  - AIM: To investigate the cardiovascular response caused by intracerebroventricular
      (ICV) microinjection of interleukin-2 (IL-2) and explore the underlying
      mechanism. METHODS: Male Sprague-Dawley rats were anesthetized with
      intraperitoneal urethane( 1.2 g/ kg). The changes of mean arterial blood pressure
      (MAP) and heart rate (HR) were observed during ICV microinjection of IL-2 with or
      without pretreatment of naloxone or atropine or phentolamine. RESULTS: There were
      no significant effects on cardiovascular response after ICV injection of IL-2 at
      500 IU/3 microl and 1 000 IU/3 microl, but IL-2 at 1 500 IU/3 microl could
      elevate MAP and HR. The responses of MAP and HR reached their maximum levels at
      10 min (MAP: 10 +/- 1.8 mmHg, HR: 25 +/- 2 b/min, P < 0.05) after the injection
      and lasted 15 or 10 minutes respectively. Pretreatment with naloxone (10
      microg/10 microl) or atropine (1.5 microg/10 microl) could block the
      cardiovascular response of ICV injection of IL-2. Pretreatment with phentolamine
      (10 microg/10 microl) failed to block the cardiovascular responses by IL-2.
      CONCLUSION: ICV microinjection of interleukin-2 (IL-2) can elevate the MAP and
      HR, which may be mediated by central opioid and cholinergic system. The alpha
      adrenergic system may be not involved in the cardiovascular response of IL-2.

PMID- 21171330
TI  - [Effect of adenosine on three dimensional tube formation and angiogenesis of
      human umbilical vein endothelial cell (HUVEC) in vitro].
AB  - AIM: To investigate the influence of adenosine on three-dimensional HUVEC tube
      formation. METHODS: A new three-dimensional culture type was established in which
      collagen type I was the substance and two layers of HUVEC grew upward and
      downward separately. In control group no adenosine was added in the holes; in
      experiment group 10(-4) mol/L adenosine was added in each hole. Under inverted
      phase contrast microscope, defined sights were observed and the number of sprout
      was recorded. Observation lasted for 96 hours, and experiments were repeated 3
      times. RESULTS: HUVEC grew upward and downward into collage gel respectively.
      Tube structure and three-dimensional network was built up gradually. In
      experiment group(adenosine 10(-4) mol/L) HUVEC grew fast with quick infiltration
      and sprouting. The tube formation was thick and might form three-dimensional
      network throughout the collagen gel. At each time point, the difference between
      experiment and control group was significant (P < 0.05 or P < 0.01). CONCLUSION:
      Adenosine may promote HUVEC sprouting and tube-formation.

PMID- 21171331
TI  - [Effects of angiotensin II on Ca2+ signal in cultured rat cardiac myocytes
      revealed by confocal laser scanning microscopy].
AB  - AIM: The effects of angiotensin II on the changes of Ca2+ signal in cultured rat
      neonatal myocytes were investigated in order to reveal the localization and
      distribution of elementary Ca2+ signaling units. METHODS: The cultured neonate
      rat myocytes were treated with angiotensin II, and calcium signal was detected
      using confocal laser scanning microscopy and fluo-4/AM calcium probe. RESULTS:
      The propagation of Ca2+ waves was observed in rest and angiotensin II stimulated
      cardiac myocytes. Calcium fluorescent intensity oscillated slightly in myocytes
      and the average intensity was much higher in the nucleus than in the cytosol, all
      of which could be magnified significantly by AngII (10(-6) mol/L). Ca2+
      oscillation induced by Ang II was completely blocked by NO donor sodium
      nitroprusside. AngII evoked Ca2+ sparks close to the cell surface membrane, and
      couldn't be abolished by sodium nitroprusside. CONCLUSION: There are
      spatiotemporal dynamics of Ca2+ signaling patterns such as Ca2+ wave, Ca2+
      spikes, Ca2+ oscillation and the whole cell Ca2+ transients induced by
      angiotensin II, which might play very important roles in cellular cardiac
      function.

PMID- 21171333
TI  - [Strychnine nitrate' effect on intracellular potentials of Mauthner cell evoked
      by skin stimulation in the crucian carps].

PMID- 21171332
TI  - [Effect of Ang II on PDGF receptor expression in vascular smooth muscle cell].
AB  - AIM: To study the effect of angiotensin II (Ang II) on platelet-derived growth
      factor(PDGF) receptor expression in vascular smooth muscle cell(VSMC). METHODS:
      Restenosis model was established by balloon injury in rat aorta. The morphologic
      change and level of Ang II were measured at 14th day after operation. The
      expression of PDGF-beta receptor was detected by Western blot. The cultured VSMC
      pretreated with or without losartan were treated with Ang II. RESULTS: Compared
      with sham group, the sections of injured aorta showed marked intimal thickening
      with large numbers of VSMCs proliferation throughout intima and media, the level
      of Ang II obviously increased by 78.8% (P < 0.05), the expression of PDGF-beta
      receptor significantly increased by 83.9% (P < 0.05) at 14th day after operation.
      The expression of PDGF-beta receptor in cultured VSMC treated with Ang II was
      higher than that of control group (P < 0.01). The effect of Ang II was inhibited
      remarkably by pretreatment with losartan. CONCLUSION: Ang II can stimulate PDGF
      receptor expression in VSMC, it may be an important mechanism of Ang II-induced
      VSMC proliferation.

PMID- 21171334
TI  - [Proteomics analysis on stressed myocardium injury-related proteins].
AB  - AIM: To probe the related proteins to stress-induced myocardium injury. METHODS:
      After establishment of a myocardium injury model induced by restraint stress in
      rats, myocardium proteins of restraint stress-treated and untreated rats were
      extracted, and the two-dimensional polyacrylamide gel electrophoresis (2-DE) maps
      of the extracted proteins were established by using the immobilized pH gradient
      (IPG) and SDS-PAGE two-dimensional electrophoresis respectively. The alterative
      protein spots were analyzed by Image Master 3.01 software and identified with
      assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF
      MS) and database searching. RESULTS: Proteomics analysis showed that there were
      10 proteins were significantly influenced by restraint stress in rat myocardium.
      After stress, proteins, including cardiac myosin heavy chain, dihydrolipoamide
      succinyltransferase component of 2-oxoglutarate dehydrogenase complex, similar to
      dihydrolipoamide S-succinyltransferase, mitochondrial aldehyde dehydrogenase, H
      (+)-transporting ATP synthase, albumin, myosin heavy chain and apolipoprotein A-I
      precursor showed increased expression. Mitochondrial aconitase and uncoupling
      protein UCP-3 showed decreased expression. CONCLUSION: These differential
      expressive proteins might be involved in stress-induced injury to myocardium.

PMID- 21171335
TI  - [Effects of 48 h sleep deprivation on dual task ability and fatigue].

PMID- 21171336
TI  - [The beneficial effect of Gingko biloba extract on myocardial impairment in
      diabetic rats].
AB  - AIM: To study the protective effect of Gingko biloba extract (EGb) against
      myocardial impairment in diabetic rats. METHODS: Morphology of effect of EGb on
      myocardium in diabetic rats was observed under light microscopy (LM) and
      transmission electron microscopy (TEM). Activity of super oxide dismutase (SOD),
      nitric oxide synthase (NOS), constitutive nitric oxide synthase (cNOS), inductive
      nitric oxide synthase (iNOS) and content of malondialdehyde (MDA), nitric oxide
      (NO) were detected biochemically in myocardial homogenate. RESULTS: It was
      manifestation as vascular degeneration and local lysis of myocardial fiber under
      LM and swelling of mitochondria, shorten of mitochondrial crest, lysis of
      myofibril under TEM, the activity of SOD decreased and the activity of NOS, iNOS,
      the content of NO, MDA increased, but the morphological changes became slight in
      EGb treatment group. Activity of SOD increased while activity of NOS, iNOS and
      content of MDA, NO decreased in EGb treatment group compared with diabetic group.
      CONCLUSION: EGb can protect diabetic myocardium and anti-lipid peroxidation and
      decrease of NO level may be involved in it.

PMID- 21171337
TI  - [Improvement and evaluation for the model of delayed myocardial ischemic
      preconditioning in rats in vitro].

PMID- 21171338
TI  - [Independent or combined effects of endothelin-1 and prostaglandin F2alpha on
      cardiomyocytes].
AB  - AIM: To elucidate the independent or combined effects of endothelin-1 (ET-1) and
      prostaglandin F2alpha (PGF2alpha) on cardiomyocytes and investigate the
      relationship between hypertrophy and apoptosis of cardiomyocytes. METHODS:
      Cultured neonatal rat cardiomyocytes were stained with FITC-conjugated phalloidin
      and eosin to detect the cardiomyocyte hypertrophy evidenced by increased
      sarcomeric structure and cell size. Cardiomyocytes were stained with Hoechst
      33258 to detect apoptotic nuclei showing features of condensation and
      fragmentation. RESULTS: Cardiomyocyte hypertrophy induced by ET-1 or PGF2, shown
      a dose dependent effect. The area of cardiomyocytes treated by 10 nmol/L or 100
      nmol/L of ET-1 for 24 h increased 68% or 84% as compared with control,
      respectively. The area of cardiomyocytes exposed to 10 nmol/L or 100 nmol/L of
      PGF2alpha for 24 h increased 28% or 106% as compared with control, respectively.
      The ET-1 and PGF2alpha had a synergic effect on cardiomyocyte hypertrophy, but
      not superimposed effect. The area of cardiomyocytes increased 80%, 122%, 96%, and
      199% in 10 nmol/L ET-1 plus 10 nmol/L PGF2, 10 nmol/L ET-1 plus 100 nmol/L
      PGF2alpha, 100 nmol/L ET-1 plus 10 nmol/L PGF2alpha, and 100 nmol/L ET-1 plus 100
      nmol/L PGF2alpha group, respectively. There were no changes in apoptotic rate of
      cardiomyocytes treated by ET-1 or PGF2alpha alone for 48 h. The apoptotic rate of
      cardiomyocytes also didn't increase in ET-1 plus PGF2alpha treatment for 24 h
      groups, but significantly increased in ET-1 plus PGF2alpha treatment for 48 h
      groups. ET-1 or PGF2alpha could induce an increase in apoptotic rate of
      hypertrophic cardiomyocytes. There was a positive relationship between
      hypertrophic extent and apoptotic rate in cardiomyocytes. CONCLUSION: The
      cardiomyocytes treated by ET-1 or PGF2alpha alone only show hypertrophy, but
      treatment of ET-1 plus PGF2alpha for 48 h induces apoptosis of cardiomyocytes.

PMID- 21171339
TI  - [Effect of swimming training on the concentration of cAMP&cGMP in rat
      myocardium].

PMID- 21171340
TI  - [Effects of adrenomedullin regulating inducible nitric oxide synthase on
      proliferation and apoptosis in hypoxic pulmonary artery smooth muscle cells].
AB  - AIM: To investigate the effects of hypoxia on the proliferation and apoptosis of
      PASMC, to evaluate the role of iNOS protein expression and ADM on the hypoxic
      pulmonary hypertension (HPH) pathogenesis. METHODS: To culture rat pulmonary
      artery smooth muscle cell (PASMC), cultured PASMC cells were grouped into:
      normoxic group; hypoxic group; hypoxia + L-NAME group; hypoxia+ ADM group.
      Proliferation of PASMC were investigated by MTT and PCNA. Apoptosis of PASMC were
      examined by flow-cytometry. Westen blot was used to measure protein expression of
      iNOS induced by hypoxia. RESULTS: (By MTT, the value of 24 h hypoxia was
      significantly higher than that in the normoxic group (P < 0.01), the value of the
      hypoxia + ADM was significantly lower than that in hypoxia group, the value of
      the hypoxia + L-NAME was significantly higher than those of hypoxic group and
      normoxic group (P < 0.01). (2) By immunohistochemistry, PCNA was poorly positive
      in PASMC, whereas positive after 24 h hypoxia (P < 0.01), ADM inhibited the
      expression of PCNA significantly (P < 0.01), whereas L-NAME increased the
      expression of PCNA significantly (P < 0.01). (3) By FCM, apoptosis index was not
      significantly different between the normoxic group, hypoxic group, hypoxia + L
      NAME and hypoxia + ADM (P > 0.05). (4) By Western blot, iNOS expression was
      poorly positive in control group, positive after 4 h hypoxia (P < 0.01),
      increasing as the hypoxia environment continued (P < 0.01). L-NAME had no effect
      on iNOS protein, ADM promoted iNOS expression (P < 0.01). CONCLUSION: (1) Hypoxia
      stimulates the proliferation of PASMC, and has no obvious effects on the
      apoptosis of PASMC. (2) Hypoxia induces the expression of iNOS, ADM can increase
      expression of iNOS, ADM and INOS plays a role of protection in HPH pathogenesis.

PMID- 21171341
TI  - [Protective effects of glucagon-like peptide 2 on intestinal ischemia/reperfusion
      injury in mice].
AB  - AIM: To investigate the protective effects of glucagon-like peptide 2(GLP-2) on
      intestinal ischemia/reperfusion (I/R) injury in mice. METHODS: Intestinal
      ischemia/reperfusion model in mice were set up and 32 mice of Kunming species
      were divided randomly into 4 groups (n=8): Sham group, I/R group, I/R + GLP-2
      group and I/R + glutamine group. The morphologic changes of intestinal mucosa
      were observed under LM. The villus height and crypt depth of intestine, the
      activity of diamine oxidase (DAO) in intestine and bacterial translocation rates
      of mesenteric lymph nodes (MLN) were detected. RESULTS: Compared with sham
      operation group, the intestinal villi were sloughed in I/R group with decreased
      villus height and crypt depth (P < 0.01), the DAO activities were decreased (P <
      0.01), and MLN bacterial translocation rates were increased (P < 0.05). While GLP
      2 administration improved the villus damage, increased DAO activity (P < 0.01),
      and decreased MLN bacterial translocation rates (P < 0.05), compared with I/R
      group. CONCLUSION: GLP-2 have protective effects on intestinal morphology and
      barrier function after ischemia/reperfusion injury in mice.

PMID- 21171342
TI  - [Cloning and sequencing of alpha, beta globin coding genes in Tibetans living at
      high altitude].
AB  - AIM: To explore the molecular biological mechanism of hemoglobin with high oxygen
      affinity in Tibetans by determining the sequence of globin cDNA in Tibetans
      living at high altitude. METHODS: Total RNA was isolated from human bone marrow
      samples of three Tibetans who live in Qinghai-Tibet plateau. cDNA fragments
      coding for alpha and beta genes of human hemoglobin were obtained through RT-PCR
      and were ligated to plasmid pGEM-T easy vectors, and then the ligation liquid
      were transformed to Escherichia coli and cloned and sequenced. Nucleotide
      sequences were compared with GenBank data by BLAST method. RESULTS: sequence of a
      globin cDNA in Tibetans were the same with the registering globin genes in the
      GenBank, and Hb Abruzzo (beta143 (H21), His- > Arg) gene mutation, a high oxygen
      affinity beta globin mutation, was found in one Tibetan' beta goblin coding gene
      (CAC- > CGC). CONCLUSION: This hemoglobin gene mutation may be associated with
      high altitude adaptation of Tibetans living at high altitude.

PMID- 21171344
TI  - [Effect of genistein on expression and current of voltage-gated calcium channels
      in mouse pancreatic beta-cells].
AB  - AIM: To determine the effect of long-term inactivation of tyrosine kinases on
      voltage-gated calcium currents in pancreatic beta-cells and to evaluate the
      function of tyrosine kinases in pancreatic beta-cells. METHODS: Primarily
      cultured mouse pancreatic islets and beta-cells were pretreated by 0.1 mmol/L
      genistein for 12 hours. Voltage-gated calcium currents and action potentials were
      recorded with patch clamp techniques in the configuration of perforated whole
      cell recording. RT-PCR method was used to evaluate the changes in expression of
      voltage-gated calcium channels alpha1 subunit. RESULTS: After treatment by
      genistein for 12 hours, the whole-cell voltage-gated calcium currents were
      significantly diminished (-13.83 +/- 1.515 pA/pF vs. -7.012 +/- 1.502 pA/pF, P <
      0.01, n=6). The amplitudes of action potentials in genistein-treated beta-cells
      were also significantly attenuated (38.50 +/- 7.46 mV vs. 15.95 +/- 4.39 mV, P <
      0.01, n=6). The expression of voltage-gated calcium channels alpha1 subunit in
      mouse islets was significantly decreased to 0.792 +/- 0.078 of that in control
      conditions (P < 0.01, n=5). CONCLUSION: Genistein treatment decreases expression
      and current of voltage-gated calcium currents in mouse pancreatic beta-cells,
      which suggests that inhibition of tyrosine kinases activity plays an important
      role in the dysfunction of pancreatic beta-cells.

PMID- 21171343
TI  - [The induction apoptosis of HL-60 cells by low molecular weight compounds of
      taurine, ornithine and carnosine from new born calf liver].
AB  - AIM: Clinical studies stated that low molecular weight compounds (< 1.0 kd)
      extracted from the new born calf liver could effectively inhibit the
      proliferation of tumor cells. In this report, we observed inhibition effects and
      their regulative mechanisms of taurine, ornithine, carnosine on the proliferation
      of HL-60 cells. METHODS: Three active ingredients, i.e., taurine, ornithine and
      carnosine were separated by ion-exchange chromatographic column and identified
      from the low molecular weight filtrate of new born calf liver. MTT assay was used
      to test the survival rate of HL-60 cells and normal lymphocytes treated by the
      three ingredients. The various effects of the three compounds on HL-60 cells were
      respectively evaluated by agarose gel electrophoresis, ESR and
      immunohistochemical methods. RESULTS: These compounds effectively inhibited the
      proliferation of HL-60 cells and induced apoptosis which was determined by
      apoptotic changes in morphology and nuclear DNA degradation. Whereas no
      inhibition effects on normal lymphocytes were observed. In addition, the results
      of ESR showed that the activity of oxygen radical within HL-60 cells treated with
      there compounds decreased to trace level. Furthermore, in the immunohistochemical
      experiments, we found that the level of p45/skp2 in HL-60 cells decreased while
      the level of p27/kip increased. CONCLUSION: The taurine, ornithine and carnosine
      compounds can selectively suppress tumor cells proliferation by regulating the
      level of cell cycle proteins.

PMID- 21171345
TI  - [The effect of ischemic preconditioning on nitric oxide of I/R myocardial cells].

PMID- 21171346
TI  - [The protective effect of low molecular weight heparin on nephropathy in rats
      with pregnancy induced hypertension].
AB  - AIM: To investigate the protective effect of low molecular weight heparin (LMWH)
      on nephropathy in rats with pregnancy induced hypertension and to study its
      possible mechanism. METHODS: The levels of the expression of renal ERK1/2 protein
      and mRNA were detected in PIH rats which were made by injection of L-NAME, normal
      pregnant rats and rats treated with LMWH by immunohistochemistry, Western
      blotting and reverse transcription-polymerase chain reaction(RT-PCR). The renal
      tissue was observed by using light microscopy. RESULTS: The expression level of
      renal ERK1/2 protein and mRNA in LMWH-treated rats were significantly lower than
      that in PIH rats, while the expression level of renal ERK1/2 protein and mRNA in
      PIH rats was significantly higher than that in normal pregnant rats (P < 0.01),
      the intensity of ERK1/2 expression had no obvious differences among 3 groups. The
      average arterial pressure and urine protein in LMWH group were decreased, but no
      decrease was observed in normal rats. Mesangial expansion and basal membrane
      thickening were obviously retarded in LMWH- treated group. CONCLUSION: LMWH has
      renal protective effect on PIH rats, whose mechanism may be associated partly
      with a down-regulation of ERK expression.

PMID- 21171347
TI  - [sEMG signal change characteristics during the short period of recovery after
      muscular fatigue with isometric contractions].
AB  - AIM: To explore the factors affect the change of sEMG signal by investigating the
      relationship between power spectral changes of sEMG signal and H+ in muscle
      during the short period of recovery after muscular fatigue. METHODS: After a
      fatiguing constriction of the muscle, its pH value would not be featured any
      apparent changes in a short period of time. However, we were able to observe the
      movement rule of the sEMG power spectrum within 30 s of its reversion duration.
      Surface EMGs of biceps brachii muscle were recorded from 8 healthy human
      volunteers during tasks. Muscle fatigue induced by isometric loading that
      included 60% of maximal voluntary contraction. Restitution of sEMG by recording 2
      s, 4 s, 6 s, 8 s, 10 s, 20 s and 30 s by the same load after the end of the
      fatigue experiments of 60% MVC. RESULTS: There was a significant monotonous
      decline in MPF during isometric fatigue contraction of 60% MVC. MPF was
      restituted rapidly in the short recovery period after muscular fatigue. It was
      recovered 26.5% of its whole declining scope only 2 s by the end of muscle
      movement, and has been reached 87.7% of its total decreasing value till 30 s
      after the exercise. CONCLUSION: Our results suggested that the accumulation of H+
      in muscle was not the only factor that affected "spectrum shift" during muscle
      fatigue. The change of CNS drive strategy might be the important mechanisms that
      attributed to the change of SEMG signal during isometric contractions.

PMID- 21171348
TI  - [Construction of antisense recombinant adenoviral vector for c-myc and its
      antiproliferative effect on rat lymphocytes].
AB  - AIM: To observe the antiproliferative effect of antisense recombinant adenoviral
      vector for c-myc on rat thymus lymphocytes. METHODS: Antisense and sense
      bacterial plasmids for c-myc were constructed. Bacterial plasmids and El detected
      adenoviral plasmid were cotransfected into 293 cells. Recombinant adenoviral
      vectors were obtained after cotransfection. The antiproliferative effects were
      assayed by MTS. The expression of c-myc mRNA was detected by RT-PCR. RESULTS: The
      results showed that antisense recombinant adenoviral vector for c-myc could
      inhibit rat thymus lymphocytes proliferation. The expression of c-myc mRNA was
      decreased after antisense recombinant adenoviral vector for c-myc was transfected
      into cells. CONCLUSION: Recombinant antisense adenoviral vector for c-myc could
      inhibit rat thymus lymphocytes proliferation.

PMID- 21171349
TI  - [Effects of cholesterol rich diet on blood coagulative and fibrinolytic
      activities in male rabbits].
AB  - AIM: To explore the effects of cholesterol rich diet on the activities of blood
      coagulative and fibrinolytic systems in male rabbits. METHODS: 14 male New
      Zealand white rabbits were randomized to cholesterol rich diet(CRD) group and
      common diet (control) group. Rabbits in CRD group were fed with 1% cholesterol
      embedded diet and those in the control group were fed with common diet. Levels of
      blood TG, TC, LDL, HDL, Lp(a), apoA1, apoB, FIB, D-dimers and FDP, PT and APTT,
      activity of ADP, AT-III, PLG and alpha2-PI were tested in all rabbits before
      given cholesterol rich diet and after 12 weeks' feeding with different kinds of
      diet. RESULTS: Levels of blood TG, TC, LDL, HDL, Lp(a), apoA1, apoB, FIB, D
      dimers in CRD group were all elevated significantly compared with those in the
      control group and the baseline levels. PT and APTT were shortened, ADP, PLG and
      alpha2-PI activity were increased in CRD group. CONCLUSION: Cholesterol rich diet
      not only is the direct cause of hyperlipidemia but also can increase the
      coagulative activity and inhibit the fibrinolytic activity and promoting the
      evolution of arteriosclerosis.

PMID- 21171350
TI  - [The changing trends of expression of VEGF and its relationship with the levels
      of NO in rat corpus luteum of pseudopregnant].
AB  - AIM: The expression of VEGF in rat ovaries corpus luteum and its expression
      pattern were observed to investigate the effect of VEGF on luteal formation and
      regression. METHODS: The model of immature rat of pseudopregnant was established
      using pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin
      (hCG), the expression of VEGF in corpus luteum was detected by
      immunohistochemistry, the levels of VEGF in corpus luteum was measured by ELISA,
      and the levels of NO in corpus luteum was measured by chemistry assay. RESULTS:
      VEGF expressed weakly in rat corpus luteum on the day 1, and enhanced gradually
      from day 3 to day 5, then went up to the peak on the day 7, and maintained to day
      9. On the day 11, the expression of VEGF began to decrease. The levels of VEGF
      were similar to the expression of VEGF. The levels of NO appeared like double
      wave. The levels increased gradually from day 1 to day 5, and peaked on the day
      7, then decreased on the day 9, while lightly increased on the day 11, and showed
      significant increase and reached the highest on the day 13, then decreased the
      lowest on the day 15. CONCLUSION: There is a intimate temporal relationship
      between the expression of VEGF and angiogenesis in corpus luteum, VEGF may play a
      role in luteum formation by improving angiogenesis mediated by NO, NO may play a
      role in luteum regression as a luteolytic during the late luteal phase.

PMID- 21171351
TI  - [Quantification of mRNA expression for angiotensinogen in rat arterial tissues by
      real-time PCR].
AB  - AIM: To develop a real-time PCR method for quantifying low abundance mRNA
      expression in rat arterial tissues and examine differential changes of
      angiotensinogen (AGT) gene expression in basilar and femoral arterial tissues
      after 8 weeks simulated weightlessness. METHODS: After 8-wk of simulation,
      basilar and femoral arteries were harvested from both simulated weightless (SUS)
      and control (CON) rats. Then total RNA was extracted and reverse transcribed. The
      real-time PCR using TaqMan-MGB probe was performed to quantify AGT mRNA
      expression. The amplification efficiency (E) of PCR was calculated from the slope
      of standard curve. The threshold cycle (Ct) was detected by changes in
      fluorescence during a real-time PCR. Finally, the relative expression ratio of
      the target gene (AGT) to the reference gene (GAPDH) was calculated using E and Ct
      according to the mathematical model derived from the equation calculating the
      starting fluorescence (Ro). RESULTS: After a 8-weeks simulated weightlessness,
      the AGT mRNA expression increased by 240 percent in basilar arterial, and
      decreased by 66 percent in femoral arterial tissues. CONCLUSION: The specificity,
      sensitivity, precision, reproducibility, and simplicity of real-time PCR method
      using TaqMan-MGB probe make it particularly suitable for quantification of low
      abundance mRNA in arterial tissue from rats.

PMID- 21171352
TI  - [A fluorospectrophotometric determination of nitrite in blood].
AB  - AIM: To establish a fluorospectrophotometric assay for the measurement of nitrite
      in blood. METHODS: Interference from hemoglobin and other blood ingredients was
      removed through sulfuric acid and phosphotungstic acid pretreatment. Fluorescence
      of 1-[H]-naphthotriazole from the reaction of 2,3-diaminonaphthalene with nitrite
      was determined with fluorospectrophotometry. RESULTS: The following conditions
      were proper: Serum or plasma was treated with sulfuric acid and phosphotungstic
      acid pretreatment for two times, 2,3-diaminonaphthalene of 0.63 mmol x (L(-1))
      was used, reaction solution pH and final pH were about 1.60 and 1.70
      respectively, solution containing 2,3-diaminonaphthalene and supernatant after
      pretreatment was water-bathed at 20 degrees C for 15 minutes. The lower limit of
      detection was 24.27 nmol x L(-1). Nitrite determined in peripheral blood of
      healthy people was (10.91 +/- 2.38) micromol x L(-1), and its 95% distribution
      range was (6.24-15.57) micromol x L(-1). CONCLUSION: It's a relatively sensitive,
      specific, simple method. It's of some value to the study of nitric oxide.

PMID- 21171353
TI  - [ACP during the development of forestomach carcinoma in NIH mice].

PMID- 21171354
TI  - [The effect of hypoxia preconditioning no binding activity of HIF-1 on the HRE
      with EPO in the hippocampus of mice].
AB  - AIM: To observe change of binding activity of HIF-1 with erythropoietin (EPO)
      hypoxia response element (HRE) in the hippocampus of mice preconditioned to
      hypoxia and explore relationship between the changes and the preconditioning.
      METHODS: The hippocampus was removed from mice exposed to hypoxia for 0 run
      (control group), 1 run (H1 group) and 4 runs(H4 group). Electrophoretic mobility
      shift assays (EMSA), chromatin immunoprecipitation (ChIP)and real time PCR were
      used to detect the change of activity of HIF-1 on HRE of EPO. RESULTS: Both in
      vitro and in vivo binding tests showed that the HIF-1 DNA-binding activities were
      increased in group H1 and markedly increased in group H4. CONCLUSION: The
      increase of HIF-1 and HRE of EPO binding activities is thought be involved in
      hypoxic preconditioning.

PMID- 21171355
TI  - [Effects of intrathecal injection of U0126 on the expression of phospho-CREB in
      spinal cord of morphine-induced withdrawal rats].
AB  - AIM: To explore effects of intrathecal injection of U0126 on morphine withdrawal
      response and the spinal Phospho-CREB expression in morphine-induced withdrawal
      rats. METHODS: All the rats were divided into 5 groups: control group, dependence
      group, withdrawal group, U0126 group (5 microg, it) and DMSO group. Morphine
      withdrawal score, touch evoked agitation scores(TEA score), immunohistochemical
      and Western-blotting technique were used to evaluate morphine withdrawal response
      and the expression of Phospho-CREB in the spinal cord. RESULTS: Intrathecal
      injection of MEK inhibitor U0126 significantly alleviated morphine withdrawal
      symptoms. Morphine withdrawal scores in U0126 group (22.5 +/- 4.09) were
      significantly lower than that of withdrawal group (28.6 +/- 4.89, P < 0.05). TEA
      score of withdrawal group was 13.5 +/- 2.55, which was significantly higher than
      that of U0126 group (10.0 +/- 2.76, P < 0.05). Phospho-CREB positive neurons in
      the spinal dorsal horn of withdrawal group were 380 +/- 71, which is higher than
      that of U0126 group (293 +/- 47, P < 0.05). Compared with withdrawal group, level
      of Phospho-CREB protein detected by Western blot in spinal cord of U0126 group
      was significantly lower. CONCLUSION: MEK inhibitors U0126 could suppress
      expression of Phospho-CREB in the spinal cord.

PMID- 21171356
TI  - [Effect of inhibiting endoxin by antidigoxin antiserum on myocardial
      ischemia/reperfusion injury in rats].
AB  - AIM: To study the effect of antidigoxin antiserum on oxygen stress induced by
      myocardial ischemia/reperfusion (MI/R) injury in rats. METHODS: Sprauge Dawley
      rats were submitted to ligate left anterior descending coronary artery 30 min
      followed by 45 min reperfusion. Experiment animals were randomly divided into
      seven groups including sham group, MI/R group, normal salina group, verapamil
      group and three antidigoxin antiserum groups from low to high dose. The left
      ventricular myocardial tissue sample of ischemia were processed and measured the
      level of endoxin and malondialdehyde (MDA), the activities of Na+, K(+) -ATPase
      and superoxin dismutase (SOD). The myocardia morphology was observed. RESULTS:
      The levels of endoxin and MDA increased and the activities of Na+, K(+) -ATPase
      and MDA were inhibited significantly in MI/R and saline groups. Including
      verapamil group in comparison to MI/R and saline groups, MDA level decreased and
      SOD activities partly reserved, meanwhile, only in three antidigoxin antiserum
      groups, the myocardial endoxin level was remarkably decreased, Na+, K(+) -ATPase
      activities were drastically increased. The myocardial histological morphology was
      significantly improved. CONCLUSION: Antidigoxin antiserum, an endoxin mutual
      clone antibody, had the effect of attenuating the damage of oxygen free radicals
      induced by MI/R via to antagonizing the inhibition effect of endoxin on
      myocardial membrane Na+, K(+) -ATPase activities.

PMID- 21171357
TI  - [The effects of bradykinin on myocardial infarction and apoptosis in remote
      preconditioning induced by skeletal muscle ischemia].

PMID- 21171358
TI  - [Effect of activation of mitochondrial ATP sensitive potassium channel and
      calcium activated potassium channel on the permeability transition of
      mitochondria from both normal and ischemic rat brain].
AB  - AIM: To clarify whether the activation of mitochondrial ATP sensitive potassium
      channel and calcium activated potassium channel can influence the permeability
      transition of normal and ischemic brain mitochondria. METHODS: spectrophotometry
      was used to determine the effect of the two mitochondrial potassium channel
      agonists on the swelling of normal and ischemic brain mitochondria respectively.
      RESULTS: In normal mitochondria, diazoxide and NS1619 could inhibit the decrease
      of calcium induced mitochondrial absorbance at 520 nm (A520), which were blocked
      by atractyloside. When compared with the normal mitochondria, mitochondrial A520
      decrease in ischemic brain was even more rapid. Diazoxide and NS1619 could still
      inhibit the calcium induced mitochondrial A520 decrease, which were blocked by
      atractyloside. CONCLUSION: Activation of mitochondrial ATP sensitive potassium
      channel and calcium activated potassium channel can protect brain mitochondria in
      vitro probably via influencing the mitochondrial permeability transition.

PMID- 21171359
TI  - [Neural pathway participates in protection of limb ischemic preconditioning
      against brain injuries induced by ischemia/reperfusion in rats].
AB  - AIM: To explore the role of femoral nerves section (FNS) on the protection of
      limb ischemic preconditioning (LIP) against cerebral ischemia/reperfusion
      injuries. METHODS: Model of brain ischemia induced by Four-vessel occlusion was
      used. LIP was performed by clamping the bilateral femoral arteries for 10 min 3
      times in a interval of 10 min. Rats with vertebral arteries permanently occluded
      were divided into sham group, cerebral ischemic group, FNS + cerebral ischemic
      group, LIP + cerebral ischemic group, FNS + LIP + cerebral ischemic group. The
      changes of neural density (ND) in the CA1 hippocampus were observed 7d after the
      sham operation or brain ischemia under thionin staining. The expression of c-Fos
      in the CA1 hippocampus was measured 6 h after the sham operation or brain
      ischemia under immunohistochemistry method. RESULTS: Thionin staining revealed
      that serious neuronal damage was visualized in the CA1 hippocampus in both
      cerebral ischemic group and FNS + cerebral ischemic group as compared with sham
      group. LIP attenuated the neuronal damage of the CA1 subfield induced normally by
      cerebral ischemia/reperfusion, and ND in LIP + cerebral ischemic group was
      significantly higher than that in cerebral ischemic group (P < 0.01). But obvious
      neuronal damage of the CA1 subfield was found in FNS+ LIP + cerebral ischemic
      group, and ND was significantly decreased as compared with LIP + cerebral
      ischemic group (P < 0.01). These results suggested that the protection of LIP
      against cerebral ischemia/reperfusion injuries might be cancelled by preceding
      section of femoral nerve. It was found that there was almost no c-Fos expression
      in the CA1 hippocampus in sham group. Changes of c-Fos expression in the CA1
      subfield in cerebral ischemic group were similar to that in sham group. But in
      LIP + cerebral ischemic group, c-Fos expression in the CA1 subfield was markedly
      increased and the number of positive cells and optical density of c-Fos
      expression were significantly higher than those in sham and cerebral ischemic
      group. c-Fos expression in the CA1 subfield was again decreased in FNS + LIP +
      cerebral ischemic group, and the number of positive cells and optical density of
      c-Fos expression were significantly lower than those in LIP + cerebral ischemic
      group. CONCLUSION: Neural pathway participated in the protective effect of LIP on
      brain, and increased c-Fos expression in the CA1 hippocampus by LIP after
      cerebral ischemia/reperfusion, might be a part of neural pathway by which LIP
      induced brain ischemic tolerance.

PMID- 21171360
TI  - [The prior occlusion of bilateral vertebral arteries during producing global
      cerebral ischemic damage model may play a protective role as preconditioning].
AB  - AIM: To study the effect of different intervals between occlusions of vertebral
      arteries and bilateral common carotid arteries on the Pulsinelli 4-vessel
      occlusion global cerebral ischemic model, and the features of ischemia of the
      brainstem and hippocampus induced by occulusion of bilateral common carotid
      arteries under the condition of occlusion of unilateral vertebral artery.
      METHODS: Eighty four adult male Wistar rats were divided into 4 groups randomly:
      control group, bilateral vertebral artery occluding group, global brain ischemic
      insult group, and unilateral vertebral artery occluding plus bilateral common
      carotid arteries occluding group. In the global brain ischemic insult group, rats
      were further divided into 24 h, 48 h, and 72 h interval subgroups according to
      the interval between the occlusion of the vertebral arteries and bilateral common
      carotid arteries. The responses including enlarging of pupils and the light
      reflex during the brain ischemia were observed. The duration of right reflex
      disappearing, the general state, and the delayed neuronal death (DND) of
      pyramidal neurons in the CA1 hippocampus of the rats after the brain ischemia
      were also observed. RESULTS: Among the global brain ischemic insult group, both
      the responses and DND were more severe in 72 h interval subgroup than those in 24
      h and 48 h interval subgroups. There was no significant difference between 24 h
      and 48 h interval subgroups. When the bilateral common carotid arteries were
      occluded under the condition of occlusion of unilateral vertebral artery, severe
      DND was observed in the CA1 hippocampus ipsilateral to the occluding vertebral
      artery, but no significant DND was observed in the contralateral CA1 hippocampus.
      CONCLUSION: The results suggested that the prior occlusion of the bilateral
      vertebral arteries during producing Pulsinelli 4-vessel occlusion global cerebral
      ischemic model might be a cerebral ischemic preconditioning that could protect to
      some extent pyramidal neurons of the hippocampus against severe ischemic insult
      induced by occlusion of bilateral common carotid arteries within 48 h. Moreover,
      There is ipsilateral predominance of blood perfusion from one side of vertebral
      artery to the brainstem and hippocampus, although there was Willis artery circle
      in rats.

PMID- 21171361
TI  - [The effects of sphingosine-1 1-phosphate (SIP) on the action potential and
      contractile in guinea pig ventricular myocardium].

PMID- 21171362
TI  - [Formalin-induced pain enhanced nitric oxide synthase expression and nitric oxide
      production in the rat hippocampus].
AB  - AIM: To observe the changes of nitric oxide synthase (NOS) activity and nitric
      oxide (NO) content of hippocampus including their time course and region
      distribution character in rat during the process of formalin-induced inflammatory
      pain as well as the pain behavior of rat. METHODS: The pain threshold (PT) was
      determined by radiant heat-induced tail flick test. NOS expression in the
      hippocampus was determined by using NADPH-d histochemical staining. NO production
      in hippocampus was determined by assaying NO3- and NO2-. RESULTS: Subcutaneous
      injection of formalin elicited nociceptive behavioural response and led to
      decrease in PT of rat. The number and staining degree of NADPH-d positive neurons
      began to increase at 6 h after the formalin injection in CA1, CA2 - 3 and DG of
      hippocampus as well as NO content, which increased most obviously at 12 h and
      returned to control level at 48 h. CONCLUSION: Formalin-induced inflammatory pain
      could induce the elevation of NOS activity in CA1, CA2 - 3 and DG of hippocampus
      with a certain time course, which further led to a increase of NO production in
      hippocampus.

PMID- 21171363
TI  - [Relationship among sexual differences of susceptibility to motion sickness, AVP
      levels of plasma and pituitary and V1b receptor expression of pituitary in rats].
AB  - AIM: To investigate the relationship among sexual differences of motion sickness
      (MS), AVP levels of plasma and pituitary and the expression of pituitary V1b
      receptors for further understanding of the MS mechanisms. METHODS: The
      conditioned taste aversion (CTA) of 0.15% saccharin sodium solution (SSS) was
      served as MS model. 98 (49 male and 49 female) rats were used in this experiment,
      50 for the detection of the AVP level in plasma and pituitary with
      radioimmunoassay (RIA), 12 for the observation of the number of V1b receptor
      positive neurons in the pituitary with the fluorescence immunohistochemistry
      method, the rest for the evaluation of the expression of V1b receptor in the
      pituitary by Western blot. RESULTS: With regard to male rats, decrease of the
      drinking volume of 0.15% SSS was greater in female rats after rotatory
      stimulation. The plasma AVP concentration of female rats was significantly higher
      than that of males under normal conditions, but reduced significantly after
      rotatory stimulation. However, no significant change was found in male rats. In
      addition, the pituitary AVP level of the female rats was significantly higher
      than that of the male rats under normal conditions, but decreased at 8 h and
      significantly at 24 h after rotation. Similarly, the pituitary AVP level of male
      rats also decreased significantly at 8 h after rotation, but this decrease was
      not comparable to that of the females. At 24 h after rotation the pituitary AVP
      level almost recovered in male rats. In the pituitary, which was related to the
      stress response, the V1b receptor-positive neurons and the expression level of
      V1b receptor in female rats were significantly higher than those of the male
      rats, but they decreased significantly after rotation, while no apparent change
      was detected in the male rats. CONCLUSION: The changes of plasma and pituitary
      AVP and V1b receptor level of the pituitary after rotatory stimulation are
      different between male and female rats and the AVP secretion of the pituitary may
      be involved in the sexual difference in susceptibility to motion sickness.

PMID- 21171364
TI  - [Experimental study of hippocampal neuronic lesion in ischemic rat by magnetic
      resonance spectroscopy].
AB  - AIM: To evaluate N-acetylaspartate reflecting the neuronal lesion in middle
      cerebral artery occlusion and reperfusion rat by magnetic resonance spectroscopy
      (MRS). METHODS: Sixteen adult Wistar rats with MCAO reperfusion and ten
      pseudooperation rats were performed MRS in vivo at the sixth weeks, then
      pathologic examination of HE staining and immunohistochemical staining were made.
      We compared hippocampus modality, cell density and immunohistochemical results
      with N-acetylaspartate, creatine changes and ration of NAA/Cr. RESULTS: The
      values of NAA, Cr and NAA/Cr of ipsilateral hippocampus lesion in MCAO
      reperfusion rats (2.05 +/- 0.33, 2.42 +/- 0.41 and 0.86 +/- 0.10) were visiblly
      decreased than contralateral hippocampus (3.45 +/- 0.58, 3.10 +/- 0.93, 1.18 +/-
      0.32) and control group (3.42 +/- 0.43, 3.57 +/- 0.47, 0.98 +/- 0.14). But the
      level of decreased NAA is not corresponding to the degree of neuronal death in
      ipsilateral region of hippocampus in histochemistry. CONCLUSION: MRS has perfect
      explanation of cell metabolic changes in CA1 region. Decrease of NAA represented
      neuron delayed injury. But the decreased level of NAA is not perfectly
      corresponded to the degree of neuron lost. This change has closed correlation
      with reactive astrocytes proliferation.

PMID- 21171365
TI  - [Effects of cyclooxygenase-1 inhibitor on spinal ERK expression in rats with
      postoperative pain].
AB  - AIM: To explore the effects of intrathecal injection of selective cyclooxygenase
      1 (COX-1) inhibitor, SC-560, on mechanical allo dynia and spinal ERK protein
      expression in rats with postoperative pain. METHODS: Rats were divided into 4
      groups: control group, postoperative pain group, SC-560 group and DMSO group.
      Mechanical withdrawal threshold (MWT), immunohistochemical and Western blotting
      technique were used to evaluate mechanical hypersensitivity and the expression of
      phospho-ERK in the spinal cord, respectively. RESULTS: (1) Behavior test rats
      developed allodynia 1 h after operation and SC-560 100 microg administrated
      intrathecally demonstrated a significant reduction in postoperative
      hypersensitivity. (2) Immunohistochemical staining Phospho-ERK positive neurons
      in the rat superficial spinal dorsal horn increased significantly 1 h after
      incision compared with that of non-incision group. Intrathecal administration of
      SC-560 preoperatively could significantly reduce the number of phospho-ERK
      positive neurons. (3) Western blot expression of phospho-ERK1/2 protein in the
      lumbar spinal cord increased significantly 1 h after incision and decreased by
      intrathecal injection of SC-560. CONCLUSION: SC-560 administrated intrathecally
      can inhibit mechanical hypersensitivity induced by postoperative pain in rats and
      this anti-allodynic process may mediated by spinal ERK.

PMID- 21171366
TI  - [Experiment research of nifedipine and vitamin K3 on ureteral action potential
      and urine flow in rabbits].

PMID- 21171367
TI  - [Change of hippocampal NMDA receptor and emotional behavior and spatial learning
      and memory in status epilepticus rat model].
AB  - AIM: SD rats were utilized for the purpose of the exploration of effects of
      status epilepticus (SE) on their emotional behavior, spatial learning and memory,
      and explorating its molecular mechanism. METHODS: Forty maturity male SD rats,
      weighing (200 +/- 20) g were divided randomly and equally into SE group (SG) and
      normal control group (NG). The SG rats were induced by Pentylenetetrazole (PTZ)
      and the control animals received a saline (0.9%) solution. The change of
      emotional behavior in two groups were tested in elevated plus maze. Furthermore,
      Morris water maze was applied to evaluate the effects by SE on spatial learning
      and memory in rats. At the same time, N-methyl-D-aspartate (NMDA) receptor NR1
      subunit mRNA in the hippocampus was determined by reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: In elevated plus test, SE rats
      increased the times of visits as well as the time spent on the open arms of the
      elevated plus maze (P < 0.01). In Morris water maze, the mean escape latency for
      the SE rats looking for hidden platform in the place navigation test prolonged (P
      < 0.01). The efficiency of their search strategy was poor (P < 0.05). The
      swimming time in platform region and the percentage of their swimming time
      decreased (P < 0.01). The number of times they crossed the platform area
      decreased (P < 0.01). Meanwhile the expression of NR1 subunit mRNA in hippocampus
      was lower (P < 0.01). CONCLUSION: The experimental results showed that SE could
      result in the change of emotional behavior and damage of spatial learning and
      memory in rats. NR1 might be involved in the patho- and physiological process in
      causing these behavioral changes.

PMID- 21171368
TI  - [An experimental research on the inhibitory action of skeletal muscle conditioned
      medium on malignant tumors].

PMID- 21171369
TI  - [A receptors in the NTS modulate depression of carotid baroreflex induced by
      intracerebroventricular injection of histamine in rats].
AB  - AIM: To investigate the roles of alpha1 and alpha2 receptors in the nucleus
      tractus solitarius (NTS) in the carotid baroreflex (CBR) resetting induced by the
      intracerebroventricular injection (ICV) of histamine (HA). METHODS: The left and
      right carotid sinus regions were isolated from the systemic circulation in 25
      Sprague-Dawley rats anesthetized with pentobarbital sodium. The intracarotid
      sinus pressure (ISP) was altered in a stepwise manner. ISP-mean arterial pressure
      (MAP) relationship curve and its characteristic parameters were constructed by
      fitting to the logistic function with five parameters. The changes in CBR
      performance induced by ICV HA and the effects of pretreatment with alpha1 or
      alpha2 receptor antagonist into the NTS on the responses of CBR to HA were
      examined. RESULTS: ICV HA (60 micromol x L(-1) in 5 microl) significantly shifted
      the ISP-MAP relationship curve upwards (P < 0.05) and moved the middle part of
      ISP-Gain relationship curve downwards (P < 0.05), and reduced the MAP range and
      maximum gain (P < 0.05). The pretreatment with phenoxybenzamine (PBZ, a selective
      antagonist of alpha1 receptor, 3 micromol x L(-1) in 500 nl) or yohimbine (YOH, a
      selective antagonist of alpha2 receptor, 2.5 micromol x L(-1) in 500 nl) into the
      NTS could obviously intensify the above-mentioned changes in CBR performance
      induced by HA, but the intensive effect of PBZ was less remarkable than that of
      YOH (P < 0.05). CONCLUSION: The intracerebroventricular administration of HA
      results in a rapid resetting of CBR and a decrease in reflex sensitivity, and the
      functions of alpha1 and alpha2 receptors in the NTS might weaken CBR resetting
      induced by ICV HA. Furthermore, alpha2 receptor in the NTS might play an more
      important role in modulating the responses of CHR to HA.

PMID- 21171370
TI  - [The effect of swimming training on the expression of cardiovascular CGRPmRNA in
      rats].
AB  - AIM: Rats cardiovascular expression of CGRPmRNA surveyed after an eight-week
      swimming training, and molecular mechanism of exercise-induced adaptation were
      studied. METHODS: 24 purebred male SD rats were divided randomly into three
      groups (n = 8): control (CR), exhaust (ER), train (TR). After swimming training
      left ventricular muscle and main artery arch were extracted, we inspected the
      expression of CGRPmRNA by RT-PCR. RESULTS: (1) Comparing with the control group,
      once exhausting exercise had no significant effect on cardiovascular expression
      of CGRPmRNA. (2) Comparing with the control group, long-term aerobic swimming
      training upregulated significantly cardiac expression of CGRPmRNA. CONCLUSION:
      Long-term aerobic training induced benign cardiac adaptation in molecular level.
      Long-term aerobic swimming training had no significant effect on vascular
      expression of CGRPmRNA.

PMID- 21171371
TI  - [Effect of AcSDKP on the proliferation and collagen synthesis in cultured rat
      cardiac fibroblasts stimulated by PDGF].
AB  - AIM: To investigate whether AcSDKP can inhibit proliferation and collagen
      synthesis in cultured rat cardiac fibroblasts mediated by PDGF. METHODS: Neonatal
      rat cardiac fibroblasts were isolated. The cell proliferation was observed by 3H
      proline incorporation assay. RESULTS: On the culture of 0.4% FBS, PDGF stimulated
      cardiac fibroblasts proliferation and collagen synthesis with a dose-dependent
      manner at the concentrations from 1 ng/ml to 20 ng/ml, in which 10 ng/ml PDGF
      reached its peak. AcSDKP at the concentration from 10(-10) mol/L to 10(-8) mol/L
      could inhibit cardiac fibroblasts proliferation and collagen synthesis mediated
      by PDGF. 10(-9) mol/L AcSDKP attained its peak on inhibiting cardiac fibroblasts
      proliferation and collagen synthesis. CONCLUSION: AcSDKP can inhibit
      proliferation and collagen synthesis in cultured rat cardiac fibroblasts mediated
      by PDGF.

PMID- 21171372
TI  - [Effects of IL-1beta on inducible nitric oxide synthase-nitric oxide system
      activity in arginine vasopressin-induced rat cardiac fibroblasts].
AB  - AIM: To explore the effects of interleukin-1beta (IL-1beta) on inducible nitric
      oxide synthase (iNOS)-nitric oxide (NO) system activity in arginine vasopressin
      (AVP)-induced rat cardiac fibroblasts (CFs). METHODS: CFs were isolated by
      trypsin digestion method. Nitric acid reductase method, spectrophotometry and
      reverse transcription-polymerase chain reaction (RT-PCR) were used to detect NO
      contents, NOS activity and iNOS mRNA expression. RESULTS: AVP significantly
      increased iNOS mRNA expressions, NOS activity and NO contents (P < 0.05) in CFs.
      IL-1beta enhanced the effects of AVP on iNOS-NO system activity in a
      concentration-dependent manner, moreover the iNOS mRNA expressions, NOS activity
      and NO contents of AVP + 3 ng/ml, AVP + 5 ng/ml IL-1beta group were both
      significantly higher than those of AVP group (P < 0.05). But when IL-1beta
      concentration increased to 5 ng/ml, the iNOS mRNA expressions, NOS activity and
      NO contents did not increase accordingly, slightly decreased instead. CONCLUSION:
      Within certain range of concentrations IL-1beta cooperates with AVP to increase
      iNOS-NO system activity in CFs.

PMID- 21171373
TI  - [Relativity between change of right ventricular function and the serum
      concentration of ET-1 in patients with cor pulmonale in plain and plateau].

PMID- 21171374
TI  - [The dynamic changes in endogenous hydrogen sulfide pathway at the early stage of
      pulmonary hypertension induced by high pulmonary flow in rats].
AB  - AIM: To explore the time-dependent changes of endogenous hydrogen sulfide system
      at the early stage of pulmonary hypertension induced by high pulmonary flow in
      rats. METHODS: Eighty male SD rats, whose weight ranged 140 - 160 g, were
      randomly divided into control group (n = 40) and shunt group (n = 40). Rats in
      shunt group were subjected to an abdominal aorta-inferior vena cava shunt to
      create an animal model of high pulmonary flow. After 1 d, 3 d, 1 week, 4 week and
      8 weeks of experiment, systolic pulmonary artery pressure (SPAP) of each rat, the
      H2S of rat lung tissue and CSEmRNA of rat lung tissue were evaluated,
      respectively. RESULTS: SPAP increased significantly as compared with those in
      control group in 1 week and 8 weeks of experiment. In contrast to control group,
      the H2S of rat lung tissue increased significantly on 3 d and in 4 weeks,
      respectively. Meanwhile, in contrast to control group, relative amount of CSE
      mRNA of lung tissues elevated significantly on 3 d and in 4 weeks, respectively.
      Moreover, SPAP and the H2S of rat lung tissue, the CSE mRNA of rat lung tissue
      correlated negatively in 1 week, 4 weeks and 8 weeks of experiment. CONCLUSION:
      Animal model of rats with high pulmonary blood flow exhibited pulmonary
      hypertension. Lung tissue H2S and CSE mRNA of rats exhibited double peaks within
      8 weeks. These results revealed that endogenous H2S system might be relevant with
      the development of pulmonary hypertension induced by high pulmonary blood flow,
      and probably, it played a protective role in the regulation of pulmonary
      hypertension, especially, at its early stage.

PMID- 21171375
TI  - [Effects of noise and CS2 on the light responses of LGB neurons in rats and their
      combined influence].

PMID- 21171376
TI  - [Leptin decreases post-septic pulmonary and intestinal FABP levels and its
      mechanism].
AB  - AIM: To detect the effect of sepsis on fatty acid binding proteins (FABP) levels
      and corresponding enzymes in lung and intestine of mice, and to explore the role
      for FABP in acute inflammation. METHODS: A sepsis model of mice made with cecum
      deligation and perforation was established, and a radioimmunoassay for FABP and
      96-well spectrophotometry assays for myeloperoxidase (MPO) and superoxide
      dismutase (SOD) which were related with clearance of free radicals,were used to
      detect their levels in lung and intestine homogenized fluids. Hematoxylin-eosin
      stain was used simultaneously to check the histopathologic chanes of both
      tissues. RESULTS: Compared with sham group (108.11 +/- 94.03 and 67.22 +/- 19.47
      ng/ml) 6 h and 12 h after sepsis, FABP levels in lung and intestine were
      significantly higher (204.98 +/- 70.72 and 154.29 +/- 60.14 ng/ml), respectively.
      Twelve hours after leptin (0.1 mg/kg i p) and indomethacin (2 mg/kg i p)
      injection, lung FABP level decreased and was lower than septic group (P < 0.05).
      Moreover, 12 h after sepsis intestinal FABP increased, but it decreased after
      leptin injection (419.80 +/- 80.06 vs 191.09 +/- 96.75 ng/ml), while indomethacin
      injection had no such effect. MPO and SOD activities in lung and intestine
      changed accordingly with time after sepsis, the effect of leptin and indomethacin
      injections on it had no significant correlation with FABP changes. CONCLUSION:
      Leptin can protect vital organ functions such as lung and intestine after sepsis,
      as FABP levels, the cellular injury marker, were significantly lower than groups
      without injection. And this effect might have no correlation with the clearance
      factors of oxygenic free radicals such as MPO and SOD.

PMID- 21171377
TI  - [Effect of ligustrazine on expression of Fas/FasL in pulmonary injury induced by
      ischemia/reperfusion in rabbits].
AB  - AIM: To investigate the effect of ligustrazine (LGT) on expression of Fas/FasL
      mRNA during pulmonary ischemia/reperfusion injury (PI/RI) in the rabbits.
      METHODS: Single lung ischemia/reperfusion animal model was used in this study.
      The rabbits were randomly divided into three groups (n = 30, in each): sham
      operated group (Sham), I/R group (I/R) and I/R + LGT group (I/R + LGT). Changes
      of several parameters which included apoptotic index (AI), wet to dry ratio of
      lung tissue weight (W/D) and index of quantitative assessment of histologic lung
      injury (IQA) were measured at 1h, 3h, 5h after reperfusion in lung tissue.
      Meanwhile the location and expression of Fas/FasL mRNA were observed. Lung tissue
      was prepared for light microscopic and electron microscopic ob servation at 1 h,
      3 h, 5 h after reperfusion. RESULTS: As compared with group I/R, Fas/FasL mRNA
      slightly expressed in intima and extima of small pulmonary artery, alveoli, and
      bronchiole epithelia in group LGT. The values of AI, W/D and IQA showed
      significantly lower in group I/R + LGT than that in group I/R at 1 h, 3 h, 5 h
      after reperfusion in lung tissue (P < 0.01 and P < 0.05). Meanwhile, abnormal
      changes of the lung tissue in morphologically were lessen markedly in group I/R +
      LGT. CONCLUSION: Ligustrazine has notable protective effects on PI/RI in rabbits
      by inhibiting Fas/FasL mRNA express in lung tissue and decreasing apoptosis.

PMID- 21171379
TI  - [Clinical study on different concentration of ropivacaine for postoperative
      patient controlled analgesia].

PMID- 21171378
TI  - [Protective role of endogenous carbon monoxide to lung and kidney tissues during
      septic shock].
AB  - AIM: To study the protective role of endogenous carbon monoxide to lung and
      kidney tissues during septic shock and its mechanism. METHODS: A rat model of CLP
      was built by using the method of CLP. The malondialdehyde (MDA) content and the
      activity of superoxide dematase (SOD) in blood, lung and kidney were detected by
      immunohistochemical technique and light microscope. RESULTS: Pathological changes
      of lung and kidney in CLP + Hemin group were lighter than CLP group, inflammatory
      reaction and lipid peroxidation were also lighter. CONCLUSION: Endogenous CO can
      protect lung and kidney from the oxidative injury. It can suppress in flammation
      and the oxidative injury caused by activated inflammatory cells, it is probably
      an important mechanism of its protective effects.

PMID- 21171380
TI  - [Investigation of IL-8Rbeta mRNA expression profile in single human neutrophil].
AB  - AIM: To validate the abundance of Interleukin 8 receptor beta (IL-8Rbeta) mRNA in
      single human neutrophil. METHODS: Human neutrophils were isolated and purified
      from volunteers, total RNA was extracted and a regular RT-PCR aiming at IL-8Rbeta
      mRNA was performed to ascertain its expression profile in human neutrophils and
      optimize the reaction conditions for the following single-cell RT-PCR procedures.
      Subsequently, single neutrophil or the cellular content was harvested to conduct
      reverse transcription and two-round PCR with the same primer pairs used before.
      Serial dilution of single neutrophil cDNA pool was carried out at the same time
      with the exact two-round PCR followed. The specificity of this single-cell RT-PCR
      procedure was verified by the BamHI restriction endonuclease digestion on the
      final cDNA products. RESULTS: Regular RT-PCR indicated IL-8Rbeta mRNA expression
      in human neutrophils. While single-cell RT-PCR was sensitive enough to detect
      trace IL-8Rbeta mRNA as predicted cDNA product could be amplified from a 10 000
      times diluted intracellular specimen from single neutrophil, which indicated an
      abundant expression of this mRNA in human neutrophil. Moreover, BamHI digestion
      on the final cDNA product clarified the specificity of this single-cell RT-PCR
      procedure. CONCLUSION: This simplified semi-quantitative single-cell RT-PCR
      procedure specifically confirmed that IL-8Rbeta mRNA was highly expressed in
      human neutrophil, which also provided the possibility of comparing mRNA abundance
      at single cell level.

PMID- 21171381
TI  - [Immuno-blot detection of hemangiopoietin in the human fetal liver].
AB  - AIM: To detect the expression of a novel protein, hemangiopoietin (HAPO), in the
      human fetal liver at the protein level. METHODS: Monoclonal antibodies (moAbs)
      against HAPO were produced by traditional hybridoma technique. Their affinities
      were calculated from the results of non-competitive ELISA and the antibodies were
      purified by protein G affinity chromatography. Expression of HAPO in the liver
      was detected by SDS-PAGE and Western blot. RESULTS: Five strains of moAbs were
      screened out in total, among which three were IgG1 and the other two were IgM.
      Their light trains were all belonged to kappa. The relative affinities of the
      three IgG1 form moAbs were 3.06 x 10(9) mol/L, 6.07 x 10(8) mol/L and 1.71 x
      10(10) mol/L respectively. After purification, the purity of the moAbs could
      reach more than 99%. HAPO expression was detected at the protein level in the
      human fetal liver, and the apparent molecular weight of the nature HAPO was very
      close to but a little higher than our recombinant one. CONCLUSION: HAPO was
      expressed in the human fetal liver at the protein level.

PMID- 21171382
TI  - [The effect of sodium 4',7-bihydroxylisoflavone-sulfonate on gastric motility and
      its mechanism in rat].
AB  - AIM: To explore the effect of sodium 4',7-bihydroxylisoflavone-sulfonate (SBIS)
      on gastric motility in rats and to analyse its mechanisms. METHODS: Using
      intraperitoneal (ip) injection and intracerebroventriular (icv) microinjection of
      drugs and recording the frequency and amplitude of contraction of gastric
      motility. RESULTS: (1) The injection (ip) of different doses of SBIS could
      decrease the amplitude of gastric motility, but it wasn't a dose-dependent
      effect. SBIS also had no effect on the frequency of contraction. (2) The ip
      injection of naloxone reversed the inhibitory effect of SBIS on the amplitude of
      gastric contraction. (3) The effect of SBIS could be increased by the ip
      injection of propranolol and be reversed by the ip injection of phentolamine. (4)
      After the ip injection of atropine, the effect of SBIS on gastric motility had
      not been changed remarkably. (5) Different doses of SBIS had been microinjected
      (icy), but only the small dose decreased the amplitude of gastric motility and
      also the frequency of contraction had not been markedly changed. CONCLUSION: Both
      the i.p. and icv injection of SBIS can inhibit the gastric motility. Its effect
      can be achieved at least not only by endogenous opioid peptide and its receptors,
      but also adrenergic neuron and its alpha-receptors. Adrenergic neuron and its
      beta-receptors are also involved in the modulating effect of SBIS.

PMID- 21171383
TI  - [Effect of beta-adrenoceptor on NO-induced attenuation in spontaneous
      contractions of ileum in mice].
AB  - AIM: To investigate the influence of L-arginine (NO donors, L-Arg) on spontaneous
      contractions of ileum in mice and study the effects of activation of beta
      adrenoceptor on NO-induced inhibition in spontaneous contractions of ileum.
      METHODS: The method of spontaneous contractions recording was used to investigate
      the effect of L-NNA, ODQ, Isoprenaline( beta-adrenoceptor agonist) and
      Propranolol (beta-adrenoceptor antagonist) on NO-induced inhibition in
      spontaneous contractions of ileum. RESULTS: (1) L-Arg inhibited the spontaneous
      contractions of ileum and had concentration-response relationship. (2) L-NNA (3 x
      10(-4) mol/L), ODQ (3 x 10(-6) mol/L) relieved the inhibitory effect of L-Arg in
      ileum . (3) Propronalol (3 x 10(-6) mol/L) decreased significantly the inhibitory
      effect of L-Arg. (4) Iso (1 x 10(-7) mol/L) increased the inhibitory effect of L
      Arg. After Iso (1 x 10(-7) mol/L) and Propronalol (3 x 10(-6) mol/L) being
      coapplied, the inhibitory effect of L-Arg was not changed. CONCLUSION: NOS
      catalyzed L-Arg and produced NO. NO exerted its inhibitory effect by the cGMP
      pathway, the activation of beta-adrenoceptor was partly involved in NO-induced
      relaxation in ileum.

PMID- 21171384
TI  - [Effects of TFE on the blood pressure and its mechanism in rats].

PMID- 21171385
TI  - [Effects of soy isoflavones on the expression of Bax mRNA and Ca(2+)-ATPase
      activity in ovaries of perimenopause rats].
AB  - AIM: To investigate the effects of soy isoflavones (SI) on the expression of Bax
      mRNA and Ca(2+) -ATPase activity in ovaries of perimenopause rats. METHODS: The
      animal model of perimenopause rats was established by unforced aging. 12 month
      old presenilins female Wistar rats were administered by intragastric (ig) with
      low (500 mg/kg), middle (158 mg/kg) and high (500 mg/kg) does of SI for 8 weeks.
      The expression of Bax mRNA in ovaries were detected by RT-PCR. Ca(2+) -ATPase
      activity in ovaries and MDA content and SOD activity in serum were detected by
      chemi-chromatometry. RESULTS: Intervention of SI could significantly decrease the
      expression of Bax mRNA in ovaries and MDA content in serum, increase Ca(2+) 
      ATPase activity in ovaries and SOD activity in serum of presenilins rats (P <
      0.05 or P < 0.01). CONCLUSION: Soy isoflavones could down-regulate the expression
      of Bax mRNA and increase Ca(2+) -ATPase activity in aged ovaries. It is probably
      one of the mechanisms to improve the function of aged ovaries in perimenopause
      rats.

PMID- 21171386
TI  - [NR2B-pERK1/2-pElk-1 signaling contributes to the avoidance learning and memory
      of rats].
AB  - AIM: To investigate whether NR2B-pERK1/2-pElk-1 signaling contributes to the Y
      maze learning and memory of rat brain. METHODS: 45 adult male SD rats were
      divided into 4 groups: (1) Ifenprodil peritoneal injection group (Ifenprodil ip,
      n = 14); (2) DMSO peritoneal injection group(DMSO ip, n = 15); (3) Ifenprodil
      cerebral ventricle injection group (Ifenprodil ic, n = 8); (4) DMSO cerebral
      ventricle injection group(DMSO ic, n = 8). Y-maze training and test were used as
      an learning and memory enhancing stimulus. Immunohistochemical and Western
      blotting methods were used for detecting pERK1/2 and pElk-1 expression intensity
      of different brain regions. RESULTS: Compared with the DMSO ip group, the
      ifenprodil ip group showed no change on the Y-maze learning score (P > 0.05), but
      its Y-maze memory score tested 24 after learning decreased (P < 0.05). Ifenprodil
      peritoneal injection made brain pERK1/2 and pElk-1 expression decreased
      generally. In hippocampus, marginal division of striatum(MrD), amygdala,these
      changes were more significant (P < 0.05). Compared with the DMSO ic group, the
      reconsolidation of Y-maze memory tested 6 hours after ifenprodil injection was
      impaired in ifenprodil ic group (P < 0.05). The OD value of pERK1/2 and pElk-1
      positive bands in ifenprodil ic group attenuated generally. The pElk-1 positive
      bands of caudate putamen and MrD almost disappeared in ifenprodil ic group.
      CONCLUSION: NR2B is essential for the formation of long-term memory,
      reconsolidation of Y-maze memory. The deactivation of NR2B by ifenprodil will
      impair these courses. Meanwhile, the deactivation of NR2B attenuates pERK1/2 and
      pElk-1 expression of learning and memory related regions after Y-maze learning
      and memory reconsolidation test. In MrD and caudate putamen, the pElk-1
      expression are completely blocked by ifenprodil after memory reconsolidation
      test.

PMID- 21171387
TI  - [New method of left ventricular intubation in anaesthetised rats].
AB  - AIM: To search for a new method of left ventricular intubation in rat. METHODS:
      The wire of percutaneous transluminal coronary angioplasty (PTCA) was put into
      carotid artery through external carotid artery. Then supported by guide wire, the
      PE50 tube was advanced into left ventricle. RESULTS: Left ventricular intubation
      with PTCA guide wire could be performed in 30 rats and successfully repeated in
      27 animals. CONCLUSION: The new left ventricular intubation technology in rats is
      simple and provides a reproducible method.

PMID- 21171388
TI  - [Glutamate-related mechanism of ginsenosides against anoxic-ischemic brain
      damage].
AB  - AIM AND METHODS: To observe the antagonist effect of ginsenosides upon excitatory
      neurotoxicity of glutamate in rat hippocampal slices, and to observe the
      inhibitory and facilitated effects of ginsenosides upon glutamate release from
      cultured mice cortical neurons and upon glutamate uptake by cultured astrocytes,
      respectively, during simulated ischemia, in order to elucidate whether the
      protective effect of ginsenosides against anoxic-ischemic brain damage is related
      to reducing the excitatory neurotoxicity of glutamate. RESULTS: The orthodromic
      population spikes (OPS) recorded in hippocampal slice decreased in amplitude and
      disappeared finally during 20-min glutamate (1 mmol/L) exposure, and recovered
      less 1 h after the end of this exposure. However, OPS recovered well after the
      use of ginsenosides at different concentrations, especially at 20 microg/ml. In
      cultured mice cortical neurons and astrocytes, glutamate released from neurons up
      to several times of control and its uptake by astrocytes decreased markedly
      during simulated ischemia, ginsenosides (20 microg/ml) could significantly
      inhibit glutamate release from neurons and facilitate glutamate uptake by
      astrocytes during the same ischemia exposure. CONCLUSIONS: Reducing the
      excitatory neurotoxicity of glutamate may be an important mechanism of
      ginsenosides against anoxic-ischemic brain damage.

PMID- 21171389
TI  - [A study on oxidative stress induces neuronal apoptosis of the cerebral cortex in
      vitro].

PMID- 21171390
TI  - [Effects of free radicals and amyloid beta protein on the currents of expressed
      rat receptors in Xenopus oocytes].
AB  - AIM: To investigate the effects of free radicals (FRs) and amyloid beta protein
      (A beta 1-40) on the functions of expressed neurotransmitter receptors (NRs) from
      rat brains in Xenopus oocytes. METHODS: Total RNA and Messenger RNA (mRNA) was
      prepared from 3-month-old Wistar rat brain tissues with Promega kits and
      microinjected into mature Xenopus oocytes (stage V - VI) with 50 nl (50 ng) for
      each oocyte for receptor expression and their currents were recorded with double
      electrode voltage clamp technique. Superoxide anion free radicals (SAFRs) and A
      beta 1-40 was added 12 h, 24 h, 96 h to incubation solution before recording.
      RESULTS: The results showed that oocytes expressed mACh, glutamate, dopamine,
      serotonin and gamma-aminobutyric acid receptors. The current characteristics of
      these receptors were inward currents carried by chloride ion with their
      equilibrium potentials close to - 22 mV. A beta 1-40 and free radicals had a kind
      of inhibitory effect on the expressed GluR. When treated with 60 nmol/L A beta 1
      40 over 24 h, the currents of GluR significantly decreased (25% off, P < :0.01).
      When oocytes were co-treated with 60 nmol/L A beta 1-40 and SAFRs over a period
      of 12 h, the currents of glutamate receptor significantly decreased (21% of P <
      0.05), and the decreased percentage reached 52% over 24h co-treated with 60
      nmol/L A beta 1-40 and SAFRs. Vitamin E had partial antagonistic effect against
      these effects. CONCLUSION: The result suggests that A beta has a kind of
      inhibitory effects upon glutamate receptor, which is similar to those of free
      radicals. Their effects can be antagonized by vitamin E. This implies that A beta
      may play roles via inhibiting receptor function in pathophysiology of Alzheimer's
      disease.

PMID- 21171392
TI  - [Synergic effects of selenium and cadmium no the electrophysiological properties
      of the rat myocardial cells in culture media].

PMID- 21171391
TI  - [Expression of a human FL eukaryotic expressing plasmid mediated by lipofectamine
      in HFCL cells].
AB  - AIM: Bone marrow stromal cell line-HFCL were transfected with the recombinant
      eukaryotic expressing vector-pIRESlneo/hFL by using liposome-mediated gene
      transfer method and get a stable expression. METHODS: HFCL cells were transfected
      with the recombinant eukaryotic expressing vector-pIRESlneo/hFL by using liposome
      lipofectamine. Integration of hFL in the genome, transcription of hFL mRNA and
      expression of hFL protein in the transfected HFCL cells were assayed by Southern
      blot, Northern blot, Western blot and ELISA, the experiment of the human
      umbilical blood CD34+ cell multiplication. RESULTS: hFL cDNA was integrated into
      HFCL genome successfully, hFL mRNA was transcripted, hFL protein was expressed
      with (60.3 +/- 0.1) ng. 10(6) cell(-1) x d(-1) and the experiment of the human
      umbilical blood CD34+ cell multiplication shows that hFL has obvious biological
      activity in the supernatant. CONCLUSION: The recombinant plasmid is proved to be
      stably expressed in HFCL cells and obvious biological activity of hFL was
      detectable in the supernatant of the transfected cells.

PMID- 21171393
TI  - [Cloning of B7-1 and B7-2 genes from human Burkitt's B lymphocyte line].
AB  - AIM: In order to construct recombinant B7-Pseudomonas exotoxin fusion protein to
      induce long-term immunotolerance, we tried to clone both B7-1 and B7-2 genes from
      human Burkitt's B lymphocyte line (Raji) and construct the recombinant plasmids
      encoding for B7-1 and B7-2. METHODS: Two pairs of primers for B7-1 and B7-2 were
      designed and synthesized according to the sequences o human B7-1 and B7-2 genes
      derived from genbank. Two recombinant plasmids pGEM-T-B7-1 land pGEM-T-B7-2 were
      constructed by recombinant gene techniques. RESULTS AND CONCLUSION: We have
      successfully cloned both B7-1 and B7-2 cDNA-which, confirmed by DNA sequencing,
      EcoRI/Hind III and BamHI/Sph1 restriction enzyme digesting, could be used to
      construct recombinant B7-Pseudomonas exotoxin fusion proteins.

PMID- 21171394
TI  - [Bilateral lesion of locus coeruleus in rats induces haemorrhage in multiple
      visceral organs].
AB  - AIM AND METHODS: The haemorrhagic changes of the urinary bladder, as well as that
      of other visceral organs, were checked histologically in rats being received
      bilateral electrolytic lesion of the locus coeruleus (LC). RESULTS: Complete
      lesion of bilateral LC constantly induced severe haemorrhage of the urinary
      bladder, accompanied with blood congestion or slight haemorrhage of other
      visceral organs. Partial lesion of bilateral LC also induced blood congestion or
      slight haemorrhage in multiple visceral organs, but the urinary bladder did not
      show haemorrhage change. Reduction of stress by adrenalectomy before lesion of
      the LC, or administration of antagonist of histamine H2 receptor, had no obvious
      effect on the haemorrhage of the urinary bladder and histological changes of
      other visceral organs. CONCLUSION: These results indicate that the haemorrhagic
      change of multiple visceral organs induced by bilateral lesion of the LC in rats
      is not due to stress, or due to involvement of histamine H2 receptor. The
      mechanism needs to be studied further.

PMID- 21171395
TI  - [Gradation metabolism of kaliuretic peptide and atrial natriuretic peptide in
      kidney in spontaneously hypertension rats ].

PMID- 21171396
TI  - [Postnatal development of brainstem auditory evoked potential and middle latency
      response in rats].
AB  - AIM: To compare the postnatal development of brainstem auditory evoked potential
      (BAEP) with that of middle latency response (MLR) in rats. METHODS: The postnatal
      development of BAEP and MLR had been studied continuously for 10 weeks in the
      same groups of rat Pups. RESULTS: BAEP and MLR emerged at day 14 and 17
      respectively. The peak latencies of BAEP's waves shortened systematically with
      age, especially during 3-4 weeks. The peak latency of wave I reached adult value
      at day 29, and the peak latencies of the rest waves reached adult ones at day 70.
      However, the peak latencies of wave Po and Na in the first time evoked MLR had
      already been at adult values. Though the peak latencies of wave Pa, Nb and Pb
      also shortened with age, they reached adult ones quickly at day 20-23. The wave
      amplitudes of BAEP's wave I ,III, IV and MLR's wave Nb, Pb increased quickly with
      age during 3-4 weeks. Their peak values were much bigger than adult ones and then
      decreased gradually. CONCLUSION: The postnatal development of BAEP and MLR
      proceeded in a similar way in rats, but the peak latencies of MLR reached adult
      values much earlier than that of BAEP.

PMID- 21171397
TI  - [The influence of acetylcholine on the proliferation of cultured human pituitary
      tumour cells].
AB  - AIM: To study the influence of acetylcholine on the proliferation, DNA synthesis
      and cell cycle of cultured human pituitary tumour cells. METHODS: MTT method, 3H
      TdR incorporation and cell cycle analysis were used to examine the changes of
      proliferation and DNA synthesis of human pituitary tumour cells. RESULTS: Ach at
      10(-7) mol/L - 10(-5) mol/L could decrease the 3H-TdR incorporation and the MTT A
      value in a dose dependent manner (P < 0.01), and the ratio of G1 phase of
      pituitary tumour cells increased markedly (P < 0.01). The effect of acetylcholine
      on the proliferation of cultured human pituitary tumour cells could be inhibited
      by atropine. CONCLUSION: Ach inhibited the proliferation, DNA synthesis and cell
      cycle of cultured human pituitary tumour cells, and the inhibitory effect was
      mediated by acetylcholine receptor.

PMID- 21171398
TI  - [The study on the differential display of gene in rat's cerebral cortex during
      hypoxia].

PMID- 21171399
TI  - [Effects of maitotoxin on the transmission of neuromuscular junction in rats].
AB  - AIM AND METHODS: The effects of maitotoxin (MTX) on neuromuscular junction
      transmission in isolated non-uniformed stretched muscle preparation of rat
      diaphragms were studied using intracellular recording with microelectrodes.
      RESULTS: (1) End-plate potentials (EPPs) were not induced abruptly after 18.0 min
      10 microg/L MTX added to the chamber. Hereafter postsynaptic membrane potential
      was depolarized gradually, and the maximum depolarization value was 27.0 mV. The
      frequency of mEPP increased markedly after 70.3 min MTX administered, 32 folds
      compared with control. (2) 20 micromol/L verapamil was added to the chamber 20
      min prior to 10 microg/L MTX. No evident effects of verapamil on the above
      parameters elicited by MTX was produced, except that it was 78.5 min when EPPs
      were not induced by train stimulation, which was longer than that was induced by
      MTX alone (P < 0.001). CONCLUSION: The predominant effect of MTX on the
      neuromuscular junction transmission was that EPPs couldn't be elicited by
      indirect stimulation, and which could be inhibited partly by verapamil, a L-type
      calcium ion channel blocker. Postsynaptic membrane potential depolarization and
      mEPP frequency increasing induced by MTX couldn't be inhibited by verapamil.

PMID- 21171400
TI  - [Effects of NMDA and non-NMDA agonists on the respiratory rhythmical discharge of
      the hypoglossal nerve in the medullary slice from neonatal rats].
AB  - AIM: To study the possible role of the NMDA and non-NMDA receptor on the
      generation and modulation of basic respiratory rhythm. METHODS: Experiments were
      performed on the medullary slices isolated from the neonatal rats. Respiratory
      rhythmical discharge activity (RRDA) of the hypoglossal nerve was recorded by
      suction electrode, then the effects of the excitatory amino acids and its
      antagonists on the RRDA were investigated by adding these drugs into the perfused
      modified Kreb's solution. RESULTS: After applying the non-NMDA receptor agonist
      KA, it was found that the respiratory circle and the expiratory time were lightly
      lengthened, but the NMDA receptor agonist NMDA had no effect on the RRDA. Both of
      the mutual antagonist DNQX and AP-5 remarkably decreased the discharge frequency
      and the integral amplitude, accompanied by the shortening of the inspiratory
      time, DNQX simultaneously shortened the respiratory circle and the expiratory
      time. CONCLUSION: During the generation and modulation of the mammalian
      respiratory rhythm, NMDA receptor may mainly play a role in the amplitude of the
      respiratory activity, the non-NMDA receptor can not only affect the amplitude of
      the respiratory discharge also modulate the frequency of the respiratory rhythm.

PMID- 21171401
TI  - [The protective effect of puerarin on cultured rat cerebral cortical astrocytes].
AB  - AIM: To study the effects of puerarin (Pue) on impairment of rat astrocytes in
      primary cell culture induced by oxygen-glucose deprivation (OGD) or sodium
      glutamate (Glu). METHODS: Astrocyte damage induced by (OGD), Glu or (+/-)-1
      aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD), as well as the action
      of Pue was measured by determining the intracellular water space (as measured by
      3-O-methyl-[1- 3H]D-glucose uptake) of astrocytes and the leakage of lactate
      dehydrogenase (LDH) from astrocytes. RESULTS: Following the exposure to OGD for 5
      h, 0.5 mmol/L Glu or 1 mmol/L trans-ACPD for 1 h, the astrocyte volume and LDH
      leakage from astrocytes were increased. 0.1 mmol/L Pue, when co-incubated with
      OGD, Glu or trans-ACPD, reduced astrocytic swelling and the LDH leakage.
      CONCLUSION: Pue had protective effects on astrocytes damaged by OGD, Glu or trans
      ACPD.

PMID- 21171402
TI  - [The effect of ischemic preconditioning on adenosine phosphate content after
      spinal cord ischemia in rabbits].
AB  - AIM: To study the effect of ischemic preconditioning (IP) on adenosine phosphate
      content after spinal cord ischemia in rabbits. METHODS: We established a lumbar
      spinal cord ischemia model by inflating the balloon of a 4F Swan-Ganz catheter
      positioned in the abdominal aorta of the rabbits. All rabbits were divided into
      sham-operated group, ischemic group and IP group. Adenosine phosphate content in
      spinal cord of all rabbits was determined at 4 hours, 2 days and 5 days after
      spinal cord ischemia by using reverse phase HPLC. RESULTS: ATP content in lumbar
      spinal cord of rabbits in ischemic group was markedly reduced (P < 0.01 vs sham
      operated group). But in IP group, it was obviously elevated at each time point
      compared with ischemic group (P < 0.01). CONCLUSION: IP can significantly
      elevated ATP content in postischemic lumbar spinal cord in rabbits. This may be
      one of the mechanisms that IP can protect spinal cord from ischemic injury.

PMID- 21171403
TI  - [Trophic effect of ciliary neurotrophic factor on denervated skeletal muscle].
AB  - AIM: The trophic effect of CNTF on skeletal muscle atrophy and dysfunction
      reduced by denervation was investigated in SD rats. METHODS: SD rats transected
      sciatic nerve in right side hind limbs were injected CNTF subcutaneously for 20
      days. Skeletal muscle wet weights, protein contents, muscle fiber cross-sectional
      areas, contract properties and degree of hind limb abnormalities were observed in
      the rats. RESULTS: (1) Administrating of CNTF (0.2 mg/kg) in sciatic nerve
      transected SD rats attenuated denervation-induced skeletal muscle fiber atrophy
      evidently, resulted in gastrocnemius in injury side an obvious increase in
      contract function, prevented the loss of weights and protein in denervated
      skeletal muscle, and ameliorated abnormalities in sciatic nerve cut limbs
      remarkably. (2) The myotrophic effect of 0.2 mg/kg CNTF is more effective than
      0.05 mg/kg. (3) The sensitivity to CNTF varied in muscles of different type; slow
      twitch muscle (soleus muscle) reacted to CNTF stronger and quicker than twitch
      muscle (extensor digitorum longus). CONCLUSION: CNTF significantly attenuates
      denervation-reduced skeletal muscle atrophy and dysfunction in SD rats, act an
      evident myotrophic effect on denervated skeletal muscle. And this effect may be
      exerted in a dosage dependent manner and varies with muscle type.

PMID- 21171404
TI  - [Effects of microinjection of L-arginine into the depressor area of ventral
      surface of medulla oblongata on cardiovascular responses].
AB  - AIM: To study the effects of L-arginine, a precursor for the synthesis of nitric
      oxide, when it was microinjected into the functionally identified depressor area
      in ventral surface of medulla oblongata (VSMd) on cardiovascular responses.
      METHODS: Artery pressure (AP), perfusion pressure of the kidney (PPK) and heart
      rate were recorded to study the effects of microinjection of NO related drugs
      into VSMd. RESULTS: (1) Unilateral microinjection of L-arginine (60 - 100 nmol)
      into VSMd produced prominent dose-related pressor effect and increased PPK but
      without significant changes in heart rate. (2) Microinjection of L-Arg (100 nmol)
      3 min after microinjection of methylene blue (10 nmol) into VSMd did not
      significantly change AP and PPK. (3) Unilateral microinjection L-glutamate (350
      nmol) into VSMd elicited depressor effect (-34.97% +/- 4.33%). The depressor
      effect was significantly dosed related attenuated by prior microinjection L
      arginine (60 - 100 nmol) into the same area. CONCLUSION: These results suggest
      that the L-arginine - NO pathway in the VSMd participate in the central
      regulation of artery pressure and the pathway may have a key role in inhibiting
      glutamatergic neurotransmission in the anesthetized rats.

PMID- 21171405
TI  - [The study of transfected cardiomyocytes by recombinant adenovirus and adeno
      associated virus].
AB  - AIM AND METHODS: Recombinant adenovirus (rAd) and adeno-associated virus (rAAV)
      were created, in which beta2-adrenergic receptors (beta2-AR) gene is under
      control of the cmv promotor, the cultured neonate rat ventricular myocytes were
      infected by the two vectors, and the expression of beta2-AR on cultured neonate
      rat ventricular myocytes was assessed. RESULTS: RT-PCR demonstrated the presence
      of beta2-AR mRNA, protein immunoblots demonstrated the expression of the beta2-AR
      gene. According to a ligand binding assay, the density of beta AR in the
      cardiomyocytes infected by rAd and rAAV had no difference, which was greater than
      that in the control. CONCLUSION: The results above demonstrated that adenovirus
      vector and AAV vector transfected efficiently cardiomyocytes.

PMID- 21171406
TI  - [Tissue distribution of cystathionine beta-synthase and its changes during the
      development of atherosclerosis in rats].

PMID- 21171408
TI  - [Effect of BH on ATP-sensitive K-channels in mouse pancreatic beta-cells].

PMID- 21171407
TI  - [Influence of myocardial ischemia/reperfusion in vitro on nuclear envelope NTPase
      activity and mRNA export in the cardiomyocyte of rabbits].
AB  - AIM: To study the alteration of nuclear envelope associated NTPase activity and
      mRNA nucleocytoplasmic transport in rabbit cardiomyocyte following in vitro
      ischemia and reperfusion. METHODS: The model of myocardial perfusion in rabbit
      was used to produce myocardial I/R injury and cardiomyocyte nuclear envelope
      vesicles were prepared by density gradient centrifugation for the assay of mRNA
      transport rate and NTPase activity. RESULTS: NTPase activity was reduced and mRNA
      transport rate was significantly decreased in I/R (P < 0.01) but not in ischemia
      group( P > 0.05). CONCLUSION: The nuclear envelope vesicles had been injured
      following ischemia and reperfusion and resulted in NTPase activity reduced and
      egress of mRNA interrupted, and therefore may lead to decreasing of protein
      synthesis.

PMID- 21171409
TI  - [Effects of osmolarity on NO synthase activity in endothelial cells and its
      mechanism].
AB  - AIM: To investigate the effects of the osmolarity on the NO synthase (NOS)
      activity in endothelial cells and explore their mechanism. METHODS: The
      endothelial cells were exposed to hypotonic (205 mOsm) or hypertonic (410 mOsm)
      in culture medium. Griess assay was used to measure NOS activity in cells. The
      inducible NOS (iNOS) and endothelial NOS (eNOS) gene expression were detected by
      Northern blot method. RESULTS: After exposed to hypotonic or hypertonic medium
      NOS activity of eEND cells increased significantly compared with that of
      endothelial cells cultured in isotonic medium (305 mOsm). The increases induced
      by non isotonic changed in time-dependent model. The effect of hypotonic on NOS
      activity was more significant than that of hypertonic. Dexamethasone had no
      effect on the increases of NOS activity induced by non-isotonic osmolarity.
      Cycloheximide suppressed NOS activity via inhibiting protein synthesis but in
      cycloheximide treated cells, but hypotonic or hypertonic still caused significant
      increase in NOS activity over the control. The results of Northern blot analysis
      showed that hypotonic and hypertonic induced the increase of eNOS gene
      expression, but had no effect on iNOS gene. CONCLUSION: Hypotonic and hypertonic
      specifically increased eNOS activity in endothelial cells, in which the increase
      of eNOS gene expression may play an important role.

PMID- 21171410
TI  - [Effect of taurine on intracellular calcium concentration of rat cardiac
      myocytes].

PMID- 21171411
TI  - [The effect of sinoaortic denervation by five selective methods on baroreflex
      sensitivity in conscious rats].
AB  - AIM: To measure the acute and chronic effects of left or/and right sinoaortic
      denervation (SAD), aortic denervation, and sinus denervation on baroreflex
      sensitivity (BRS) in conscious rats. METHODS: BRS was measured by means of a
      modified Smyth's method. The acute and chronic effects experiments were executed
      in 1st and 21st days after selective SAD respectively to compare the compensatory
      function. RESULTS: (1) BRS decreased significantly after selective SAD. BRS of
      right SAD was significantly lower than that of left SAD, but they were able to
      compensate for each other. (2) The decrease in BRS of aortic denervation was more
      significant than that of sinus denervation, but the former had no significant
      compensatory function, which was different from the latter. CONCLUSION: As for
      baroreflex, right sinoaortic nerves are more important than the left, but their
      ability to compensate for each other is comparable. Meanwhile, aortic nerves are
      more important than sinus nerves, and so is their compensatory function.

PMID- 21171412
TI  - [Study on protective mechanism of metallothionein in cardiomyocytes].

PMID- 21171413
TI  - [The vasodilation and its mechanism of C-type natriuretic peptide].
AB  - AIM AND METHODS: With routine blood vessel perfusion in vitro, the vasodilation
      and its mechanism of C-type natriuretic peptide, a new member of natriuretic
      peptide family were observed in rabbits. RESULTS: CNP had the dose-dependent
      vasodilation effects on abdominal artery and celiac vein at the range of 10(-10)
      10(-6) mol/L, its action on vein was just like nitroglycerin, its action on
      artery was weaker than that of ANP. Atropine (10(-7) mol/L), Regitine (20
      microg), and indomethacin (20 microg) had nothing effect on the vasodilation of
      CNP on abdominal artery. But glibenclamide (10(-6) mol/L) and propranolol (10(-6)
      mol/L) could decrease the vasodilation of CNP obviously, in addition, CNP
      couldn't inhibit the vasoconstriction of NE. CONCLUSION: (1) CNP might be kind of
      venous systemic vasodilator, and it was also a arterial selective peptide
      controlling the vessel tone. (2) CNP dilated the vessel at least through two
      ways: (a) ATP-sensitive K+ channel, (b) beta-receptor.

PMID- 21171414
TI  - [The changes of function and morphology of pulmonary arterial vessels in the pika
      at high altitude].
AB  - AIM: To investigate the possible mechanisms of adaptation to chronic hypoxia in
      the pulmonary circulation. METHODS: We made direct measurements of pulmonary
      arterial pressure (Ppa) in 10 awake pika rodents that were transported to 2 260 m
      after being captured at 4 300 m and in 10 Wistar rats in a decompression chamber
      (simulated altitudes of 4 300 and 5 000 m) Ppa was obtained at 1 h of exposure to
      each simulated altitude. RESULTS: Ppa in the pikas after the 4 300 m and 5 000 m
      altitude exposed did not significantly increase whereas in the rats Ppa rose
      significantly. The ratio of right ventricular to left ventricular plus septal
      weight in the pikas and rats was 0.22 and 0.45 respectively. The pikas maintained
      levels of Hb, hematocrit and 2.3-diphosphoglycerate lower than those of the rats.
      The percent wall thickness of the small pulmonary arteries in the pikas and rats
      was 9.22 and 27.21%, respectively, and it was well correlated with the degree of
      Ppa in both groups. Mast cells were observed in the lung of the rats (7.1 +/-
      0.33 cells/mm2) but not in the pikas, There was highly positive staining for mast
      cell tryptase around pulmonary vessels in the rats, whereas no demonstrable
      reaction was observed in the pikas. CONCLUSIONS: The pika has adapted to high
      altitude by losing hypoxia pulmonary vasoconstriction and thin-walled pulmonary
      arterioles. In rats, mast cells may play an important role in the remodeling of
      pulmonary vessels by activating some growth factors.

PMID- 21171415
TI  - [Effects of simulated microgravity on the contents of monoamine transmitters in
      human plasma during heat stress].
AB  - AIM AND METHODS: Using high performance liquid chromatography-electrochemistry
      detection method to study the effects of simulated microgravity of a 7-day bed
      rest in - 6 degrees head-down title (HDT) position, heat stress and their
      combination on the contents of monoamine transmitters in human plasma, the aim of
      the present study is to examine effects of simulated microgravity on the contents
      of monoamine transmitters during heat stress and to investigate the mechanism of
      human responses to heat stress in spaceflight. RESULTS: (1) The content of 5-HT,
      NE, E did not change significantly (P > 0.05) after simulated microgravity alone.
      (2) Exposed to heat stress alone, the content of 5-HT produced a marked decrease
      (P < 0.01) at > 40 degrees C, while the contents of NE, E had manifested
      increases (P < 0.01) at > or = 50 degrees C. (3) Under the effect of the
      combination of simulated microgravity and heat stress, compared with control
      group, there was a significant decrease in the content of 5-HT (P < 0.01), but
      NE, E did not change significantly (P > 0.05). Compared with heat stress alone,
      there was a significant decrease in the content of NE, E (P < 0.001), while 5-HT
      did not change significantly (P > 0.05). CONCLUSION: Simulated microgravity
      decreased the content of heat-induced NE, E, significantly, and the suppression
      probably plays an important role in degraded human response to heat stress in
      spaceflight.

PMID- 21171417
TI  - [The radioimmunoassay of growth hormone and prolactin and its application].
AB  - AIM: To set up a highly specific and sensitive double antibody radioimmunoassay
      (RIA) for determining the contents of growth hormone (GH) and prolactin (PRL) in
      pituitary and plasma of rats; To study the effects of acute hypoxia on GH and PRL
      of rats. METHODS: We use chloramine-T technique iodinate antigen and choose the
      equilibration and saturated procedure of RIA to add the preparations. RESULTS:
      Exposed to 7 km-hypoxia for 0.5 h, pituitary GH content increased (P < 0.05) and
      conversely, plasma GH levels were suppressed (P < 0.05); while the PRL levels in
      both pituitary and plasma were suppressed (P < 0.01); and there was no
      significantly difference between 5 km hypoxia groups and control. CONCLUSION: We
      have successfully established the method of radiolabel and double antibody RIA
      with highly sensitivity; acute hypoxia (7 km) suppressed the secretion of GH and
      PRL in rats.

PMID- 21171416
TI  - [The effect of Astragalus membranaceus (Fisch) bge. on lipid peroxidation and NO
      level of myocardium from rats with diabetic nephropathy].
AB  - AIM: To study the effect of astragalus membranaceus (Fisch) bge. on the lipid
      peroxidation and NO level of myocardium from rats with diabetic nephropathy.
      METHODS: Male wistar rats were divided into five groups: (1) A normal control
      group, (2) Diabetes group, (3) Diabetic nephropathy group, (4) Diabetic
      nephropathy group complicated with acute renal function damage, (5) Astragalus
      membranaceus (Fisch) bge. treatment group. The activity of superoxide dismutase
      (SOD), glutathione peroxidase (GSH-Px), nitric oxide synthase (NOS) and content
      of malondialdehyde (MDA), nitric oxide (NO) was determined biochemically from
      myocardial homogenate among different groups. RESULTS: The activity of GSH-Px,
      SOD decreased and the content of MDA, NO and NOS activity increased in each
      experimental group compared with control group, as was more obvious in diabetic
      nephropathy group with acute renal function damage, which astragalus membranaceus
      (Fisch) bge could improve. CONCLUSION: Astragalus membranaceus (Fisch) bge. could
      protect the myocardium in diabetic nephropathy by inhibiting lipid peroxidation
      and decreasing the level of NO.

PMID- 21171418
TI  - [Isolation of specific expression gene in human fetal liver by representational
      difference analysis].
AB  - AIM: To isolate specific gene expressed in human fetal liver tissue and find out
      genes with important biological functions. METHODS: mRNA obtained from 4-months
      human fetus liver tissue was used as tester, and mRNA obtained from adult liver
      tissue was used as driver, and representational difference analysis (RDA) was
      performed. The subtracted final product was subcloned into the pGEM-T easy
      vector, after transformation, bacterial colonies were randomly picked, and 54
      plasmid clones with inserts were purified and sequenced. The homology search of
      genes was performed by online-based BLAST program through the nonredundant and
      EST database at Nation Center of Biotechnology Information (NCBI), the expression
      pattern of novel gene was further verified by competitive PCR. RESULTS: Marker
      with alpha-globin gene family, its expression frequency in subtractive cDNA pool
      is 7 times than non-subtractive cDNA library, and the pool contains many genes
      closely relative with liver growth. These show that RDA is an effective method to
      isolate gene differential expression. Through sequencing some clones, we get two
      sequences not reported before. CONCLUSION: The library is a useful means to study
      genes expressed specially in fetal liver.

PMID- 21171419
TI  - [Studies for a new type of intellectualized multifunctional training system of
      rats behaviour].
AB  - AIM: To develop a type of multifunctional training examining system of rats
      controlled by computer-gradient voltage automatically driving rats and computer
      showing, recording and analysis experimental results at right moment. METHODS:
      Adopting the imitating Windows, using Turbo C2.0 to edit software and operating
      the interface of hardware directly by means of TC, so that collecting, processing
      of signals and managing of experimental instruments are completed. RESULTS: This
      system has realized that gradient voltage automatically driving rats; phonic,
      optical and electrical conditioned stimulation; multiple path automatically set;
      the results in accordance with data base are directly processed by SAS software.
      CONCLUSION: This system has a high-grade automation. The operation is simple and
      convenient. And data processing is scientific and accurate. It is also suitable
      for developing of acoustic, visual and another special memory model of rats.

PMID- 21171420
TI  - [The improvement and discussion of the model of focal cerebral
      ischemia/reperfusion with suture-occluded method in rats].
AB  - AIM: To supply a simple method of the model of focal cerebral
      ischemia/reperfusion in rats. METHODS: Zea Longa's suture-occluded method was
      improved and the comparison between the two methods was made in rCBF, the scores
      of neurological deficit and infarct volume. RESULTS: There were not significant
      differences between our improved method and Zea Longa's method in rCBF, the
      scores of neurological deficit and infarct volume. CONCLUSION: The model of focal
      cerebral ischemia/ reperfusion with our improved method was also stable and
      established more easily than that with Zea Longa's method.

PMID- 21171421
TI  - [Advance of therapeutic angiogenesis in coronary heart disease].
AB  - A Review: Angiogenesis is an important biological phenomenon existed in ischemic
      diseases, tumor, and other diseases. Therapeutic angiogenesis is a frontier area
      in the treatment of coronary heart disease. The mechanisms and clinical
      application of therapeutic angiogenesis in coronary heart disease were briefly
      reviewed in this article.

PMID- 21171422
TI  - [Effect of MMS from the plasma of chronic renal failure patients on rats'
      myocardial contractility].

PMID- 21171423
TI  - [Experimental study on role of nitric oxide in hepatic ischemia and reperfusion
      injury].

PMID- 21171424
TI  - [Role of substance P in pressor response of nucleus ventromedialis to glutamate].
AB  - AIM: To analyze mechanism underlying pressor response of the nucleus
      ventromedialis (NVM) to glutamate. METHODS: Effects of different drugs delivered
      by intra-brain or i.v. injections on blood pressure and heart rate were observed
      in rats. RESULTS: (1) Excitation of the NVM by L-glutamate (Glu), injection of
      substance P (SP) into the nucleus dorsomedialis (NDM), nucleus paraventricularis
      (NPV) or rostral ventrolateral medulla (RVL), all induced pressor responses. (2)
      NVM pressor responses could be attenuated by preinjection of [D-Pro2, D-Phe7, D
      Trp9]-SP (DPDPDT, a substance P antagonist) bilaterally into the NDM, NPV or RVL,
      but preinjection of atropine into the RVL had no such effect. (3) Phentolamine
      (i.v. ) also reduced the NVM pressor response, but propranolol or methyl atropine
      (i.v.) had no significant effect. CONCLUSION: The NVM SPergic neurons can
      activate NDM SPergic neurons, which proceed to excite the NPV pressor area (SP
      receptor) and RVL (SP receptor)-sympathetic vasoconstrictor nerve system, thereby
      induce pressor response. The cardiac sympathetic and cardiac vagal nerves are not
      involved in this response.

PMID- 21171425
TI  - [A comparative study of the levels of plasma biological active peptide in
      hypertension and exercise-induced cardiac hypertrophy in rats].

PMID- 21171426
TI  - [Effects of ischemia/reperfusion on the phosphotyrosine proteins contents in
      hippocampus].
AB  - AIM AND METHODS: The effects of three drugs including ketamine(KT), a
      noncompetitive antagonist of NMDA receptor (NR), nifedipine(ND), a voltage gated
      calcium channel (VGCC) antagonist and 6, 7dinitroquinoxaline -2, 3-dione(DNQX), a
      non-NMDA receptor antagonist on the contents of phospho-tyrosine proteins (p-tyr
      pr) in the synaptosomal(P2), the crude membrane (P3), and the cytosolic (S3)
      fractions of hippocampus in forebrain ischemia of mongolian gerbils were studied.
      RESULTS: (1) the contents of p-tyr-pr in all three fractions (P2, P3, S3)
      decreased 15 min after ischemia, but the contents of p-tyr-pr in S3 fraction
      decreased more obviously than the others did, With the increase of reperfusion
      time, the contents of p-tyr-pr in all of these fractions recovered gradually, but
      the p-tyr-pr in S3 fraction increased more rapidly among them, in the P2
      fraction, the contents of p-tyr-pr increased slowly, but significantly and
      sustained longer during reperfusion when compared with that of P3 did. (2) The
      increase in p-tyr-pr contents induced by cerebral ischemia/reperfusion was
      partially antagonisted by KT and ND administration prior to cerebral ischemia,
      under these conditions, DNQX has no effect on it. CONCLUSION: the increase of p
      tyr-Pr contents induced by cerebral ischemia/reperfusion is related to NR channel
      and L-type VGCC, but not to non-NR channel.

PMID- 21171427
TI  - [Changes in serum T3, T4 and TRH contents of hypothalamus induced by hypoxia in
      rats].

PMID- 21171428
TI  - [The types of respiratory neurons in nucleus paragigantocellularis lateralis in
      rats and their responses to some medicines].
AB  - AIM AND METHODS: In 36 anesthetized spontaneously breathing Sprague-Dawley rats,
      the types of respiratory neurons and the state of neurotransmitters and receptors
      in nucleus paragigantocellularis lateralis (PGCL) were studied with extracellular
      recording technique and multibarrel microelectrode techniques. RESULTS: At the
      caudal part of the PGCL(cPGCL) in 14 rats, a total of 39 respiratory neurons
      (RNs) were recorded including 24 inspiratory, 12 expiratory and 3 phase-spanning
      neurons. At the cPGCL in another 22 rats, we discovered that out of 14 RNs
      tested, 12 were excited by iontophoretic application of sodium glutamate (L-GLu),
      and all the 22 RNs tested were inhibited by gamma-aminobutyric acid (GABA). DL-2
      amino-5-phosphonovaleric acid (AP5), an antagonist of N-methyl-D-aspartate (NMDA)
      receptor, and bicuculline (BIC), an antagonist of GABA(A) receptor, both showed
      three kinds of effects on the RNs discharge: excitatory, inhibitory and no
      effect. AP5 could block partially the excitatory effect of L-GLu on a large part
      of RNs tested (6/9). BIC blocked, partially or completely, the inhibitory effect
      of GABA also on a large part of the RNs tested (9/11). CONCLUSION: It is implied
      that PGCL is one of the important neural substrates responsible for the
      regulation of respiration. There might exist endogenous glutamate and GABA acting
      as neurotransmitters in the cPGCL area and excitatory amino acids (including NMDA
      and non- NMDA) and GABA(A)-receptors on cPGCL neurons. These neurotransmitters
      and receptors may mediate the regulatory action of cPGCL on respiration.

PMID- 21171429
TI  - [Effects of temperature on the open-channel density of delayed rectifier K+
      channels in hypothalamic neurons].
AB  - AIM AND METHODS: To observe the effect of temperature on multi-order open of
      delayed rectifier K+ channels in hypothalamic-neurons by cell-attached mode of
      patch-clamp technique. RESULTS: With temperature raising, the probability of open
      channel recording increased, multichannel open occurred. The density of open -
      channel on membrane of 32 degrees C, 37 degrees C and 39 degrees C was 0.71, 1.22
      and 1.82 channels/microm2 respectively (P < 0.05). CONCLUSION: More Ik of
      hypothalamus opened with temperature raising, this benefited to the body
      temperature regulation of neurons in hypothalamus.

PMID- 21171430
TI  - [Calcium signals induced by glutamate in rat hippocampal neurons].

PMID- 21171431
TI  - [Effects of intermittent hypoxia on long-term potentiation in hippocampal dentate
      gyrus of rat].
AB  - AIM: To investigate the effects of intermittent hypoxia on the hippocampal
      synaptic plasticity in rat. METHODS: The evoked potentials were recorded
      extracellularly, then the LTP were induced by tetanic stimulation in rat
      hippocampal dentate gyrus. RESULTS: Compared with control group, the amplitude of
      LTP was significantly reduced in hippocampus of rat treated with intermittent
      hypoxia. CONCLUSIONS: The present results suggest that the hippocampal synaptic
      plasticity could be decreased by the treated of intermittent hypoxia.

PMID- 21171432
TI  - [Effect of burn on the contents of ET-1 in the SON and PVN of hypothalamus,
      hypophysis, and plasma in rats].

PMID- 21171433
TI  - [Effects of hypothyroidism on Goalpha gene expression in hippocampus and dentate
      gyrus during early development of rat brain].
AB  - AIM: To study the expression of Goalpha mRNA in hippocampus and dentate gyrus of
      7-day rats with hypothyroidism. METHODS: We use wistar rat model of
      hypothyroidism and non-radioactive in situ hybridization technique to observe the
      changs of Goalpha mRNA levels in hippocampus and dentate gyrus of 7-day rats with
      or without hypothyroidism. RESULTS: Perinatal hypothyroidism can increase Goalpha
      mRNA levels in all areas of hippocampus and dentate gyrus of 7-day rats.
      CONCLUSION: Thyroid hormone can down-regulate Goalpha gene transcription in
      hippocampus and dentate gyrus during the early development of rat brain.

PMID- 21171434
TI  - [Effect of microsectioning medulla, pH and temperature on rhythmical respiratory
      discharge activity of medulla-spinal preparation isolated from newborn rat].
AB  - AIM AND METHODS: The brain stem and the spinal cord were isolated from 0-4-day
      old rats, placed in a bath and perfused with artificial cerebrospinal fluid
      (aCSF) in vitro. Spontaneous rhythmic neural activity could be recorded from
      phrenic (C4v, C5v) and hypoglossal nerves (XII). By microsection of medulla of
      medulla-spinal preparation, rhythmical respiratory discharge activity (RRDA) of
      C4v, C5v and XII were observed. RESULTS: Medulla-spinal preparation survival
      about six to eight hours when preparation was perfused continuously with aCSF.
      RRDA of C4v or C5v and XII was synchronous and continued about four to six hours.
      RRDA of C4v or C5v and XII could not be perturbed until a level of 500 microm
      rostral to obex was reached when cutting brain stem coronally in a rostral-to
      caudal direction, and until a horizontal plane at middle level was reached when
      cutting brain stem dorsal-ventrally from dorsal surface of the stem. RRDA of XII
      also could not be perturbed until a level just caudal to the caudalis root of the
      XII (50 micro m caudal to the obex) when cutting brain stem caudal-rostrally.
      Frequency of respiration gradually decreased and amplitude of RRDA gradully
      enhanced when pH of fluid perfused from 7.45 up to 7.85, and RRDA enhanced when
      from 7.35 down to 6.85 and ceased when 4.5 RRDA enhanced when temperature of
      fluid perfused from 27 degrees C up to 37 degrees C, and decreased when from 38
      degrees C up to 41 degrees C and when from 27 degrees C down to 23 degrees C, and
      ceased when 42 degrees C or 22 degrees C. CONCLUSION: A respiratory rhythm
      generating site is located in mNRF, there are neurons those are susceptible to
      change of pH and temperature in mNRF.

PMID- 21171435
TI  - [Death manners of primary cultured hippocampal neurons of rats in response to
      excess corticosterone exposure].
AB  - AIM AND METHODS: The death types of rat hippocampal neuronal cells in primary
      culture under various doses of corticosterone were questioned by in situ staining
      methods. RESULTS: CORT triggered two cellular death pathways: necrosis and
      apoptosis. Moreover, high concentrations of CORT increased the necrotic and
      apoptotic percentages in dose-dependent and time-dependent manners. CONCLUSION:
      The factors that lead to hippocampal neuronal cells necrosis or apoptosis induced
      by CORT may be contributed by the impaired of energy metabolism and the
      vulnerability of neurons to the excess glutamate neurotoxicity.

PMID- 21171437
TI  - [Inhibitory effects of nitric oxide and atrial natriuretic peptide on the
      increase in renal afferent nerve activity induced by intrarenal arterial
      injection of ET-1 in anesthetized rats].
AB  - AIM AND METHODS: By using electrophysiological technique, the effects of nitric
      oxide (NO) and atrial natriuretic peptide (ANP) on renal afferent nerve activity
      (RANA) induced by intrarenal arterial injection of endothelin-1(ET-1) were
      examined in anesthetized rat. RESULTS: (1) In response to intrarenal arterial
      injection of ET-1 (1 microg/kg) MAP was initially decreased and subsequently
      increased, and RANA was increased to 208.33 +/- 16.60% (P < 0.001). (2)
      Pretreatment with L-Arg or ANP could effectively inhibit the above biological
      actions induced by ET-1. CONCLUSION: Intrarenal arterial injection of ET-1 can
      markedly induce the increase in RANA, an effect which is abolished by L-arg or
      ANP administered by the same route.

PMID- 21171438
TI  - [Studies of interrelations between functions of lung ventilation and blood Zn,
      Cu, Fe, Ca, Mg for sportsman in Shenyang District after winter training].

PMID- 21171439
TI  - [Effects of insulin on production of NO and NOS mRNA expression in bovine aortic
      endothelial cells].
AB  - AIM: In order to explore the regulation of the production of nitric oxide (NO)
      and the expression of nitric oxide synthase (NOS) gene in bovine aortic
      endothelial cells (BAEC) by insulin. METHODS: The NO2- which is the production of
      NO in the culture medium was determined based on Griess reaction. Quantitative
      RT/PCR technique was performed to quantitate the levels of NOS mRNA in BAEC.
      RESULTS: (1) Insulin neither affected BAEC proliferation, nor had cytotoxic
      effect. (2) Over a concentration range of 1-15 microg/ ml, insulin stimulation of
      BAEC resulted in a dose-dependent production of NO in the culture supernatants 2
      hours later, with a maximum at 12 hours and this effect was completely blocked by
      L-NAME. (3) NOS mRNA was slightly greater in BAEC after exposed to insulin, but
      without statistical significance. CONCLUSION: Since the endothelial cell
      proliferation and the expression of NOS mRNA was not affected with insulin, our
      data suggested that the insulin-induced NO production was mediated via the
      activation of NOS activity.

PMID- 21171440
TI  - [Effects of long-term physical training on age-related changes of energy
      transformation of mice heart mitochondria].
AB  - AIM AND METHODS: To observe effects of long-term physical training (running
      wheel) on the age-related changes of energy transformation of mice heart
      mitochondria. RESULTS: RCR and ADP/O decreased with age in the presence of a
      ketoglutaric acid, especially in the late of age, which indicated that oxidative
      phosphorylation coupling decreased in the aging process. CONCLUSION: Adaptive
      changes of mitochondria were brought by long-term physical training which might
      delay the age-related decline of mitochondrial function.

PMID- 21171441
TI  - [The effect of hypoxic preconditioning on myocardium energy metabolism].
AB  - AIM AND METHODS: To evaluate the protective effects of hypoxic preconditioning
      (HPC) on myocardial energy metabolism, Langendorff-perfused hearts, exposed to
      HPC, were subjected to hypoxia/reoxygenation (5/10 min). 31P NMR was used to
      sequentially follow the time courses of high energy phosphates (HEP) contents and
      intracellular pH (pHi) of the rat myocardium. RESULTS: The Contents of
      Phosphocreatine (PCr), Adenosine Triphosphate (ATP) and the PCr/Pi (inorganic
      phosphate) ratios decreased during 30 min hypoxia, but the reduction was slower
      for the HPC group compared with Control. Reoxygenation induced recovery of
      myocardial HEP in both groups, HPC enhanced t he recovery especially in initial
      stage o f reoxygenation. However, pHi change was not significant for HPC group in
      this experiment. CONCLUSION: HPC improves the myocardial energy metabolism level
      during prolonged hypoxia and subsequent reoxygenation and protects myocardium
      against hypoxia/reoxygenation injury.

PMID- 21171442
TI  - [A study of the effect of captopril on prevention and treatment of hypertrophy
      and its mechanism].
AB  - AIM AND METHODS: To study the effect of captopril, angiotensin converting enzyme
      inhibitor, on prevention and treatment of hypertrophy and its mechanism, We made
      a research on the relationship between the effect of captopril on
      antihypertrophic and metabolism of catecholamines, oxygen free radicals, cations
      contents in myocardial tissue. RESULTS: (1) HW, LVW, HW/BW and LVW/BW of
      captopril group were significantly lower than hypertrophy group; (2) Captopril
      effectively prevented the depletion of myocardial NE. DA contents and elevation
      of E content that occurred in hypertrophy group; (3) Captopril promoted
      myocardial SOD. GSH-Px activities and decreased LPO content; (4) Captopril
      significantly prevented the increase of myocardial Na+, Ca2+ contents and the
      decrease of K+ content. CONCLUSION: Captopril may effectively prevent and treat
      myocardial hypertrophy. The effect of captopril is due to not only inhibiting the
      metabolism of RAS, but also regulating and improving the metabolism of
      catecholamines, oxygen free radicals, cations contents in heart.

PMID- 21171443
TI  - [Changes of erythrocyte rheology properties in immigrant subjects at different
      altitudes and its mechanism].
AB  - AIM: To explore the influence of altitude changes on red blood cell rheology
      properties and negative effects caused by it and possible mechanism. METHODS:
      Erythrocyte filtration index (EFI), superoxide dismutase (SOD) and
      Malondialdehyde (MDA) were detected the mechanisms in which EFI changes. RESULTS:
      EFI increased with increasing altitudes and there was a significant different in
      EFI at the different range of Hb at the same altitude and a significant different
      in EFI at the similar range of Hb at different altitudes. Correlative analyses
      showed that EFI was in a negative correlation with SOD activities, relations
      between EFI and MDA were on the contrary. CONCLUSION: Changes of SOD and MDA with
      increasing altitudes lead to abnormalities of erythrocyte rheology properties in
      healthy subjects.

PMID- 21171444
TI  - [Vacuole formation and endothelial damage in microvessels after ischemia
      reperfusion].
AB  - AIM: Damage of endothelial cells and adhesion of leukocytes and platelets were
      studied in rat mesentery microvessels after ischemia reperfusion. METHODS: The
      model was made by losing blood and reperfusion from carotid artery in rat.
      Changes of mesentery microvessels were observed by high magnify microscope.
      RESULTS: Leukocytes and platelets adhesions were found in venules and co
      capillaries 1-3 hours after ischemia reperfusion. Endothelial cells were edema
      and vascular walls were thickening. Vacuoles formed in intracytoplasm of some
      vascular endothelium and some bigger endothelial vacuoles prominence toward the
      luminal surface. Vacuoles liked circle shape and the diameter was 10-30 microm.
      More vacuoles were found in arterioles, even there were several vacuoles in a
      arteriole. The biggest vacuole almost occupied 2/3 of vascular lumen. CONCLUSION:
      Edema and vacuole formation in vascular endothelium indicate that endothelial
      cells are injured seriously after ischemia reperfusion.

PMID- 21171445
TI  - [Effects of hypoxia on proliferation of pulmonary arterial smooth muscle cells].
AB  - AIM: To investigate the effects of hypoxia on the proliferation of different
      diameter intra-pulmonary artery smooth muscle cells (PASMCs), and to study the
      possible signal transduction pathway in proliferation caused by hypoxia. METHODS:
      PASMCs were isolated from three different size of pulmonary arteries (>1 000
      microm, 500-800 microm, 300-400 microm diameter) and cultured separately. 3H-TdR
      incorporation and cell number were used to measure cell proliferation. RESULTS:
      3H-TdR incorporation and cell number of PASMCs from three sizes of pulmonary
      artery (> 1 000 microm, 500-800 microm, 800-400 microm diameter) increased 23.5%
      and 11.1%, 60.0% and 33.8%, 141.4% and 52.0%, respectively. Calcium antagonist
      (verapamil), PKC inhibitor (staurosporine), and Na(+)-H+ exchange inhibitor
      (amiloride) were used in PASMCs isolated from 300-400 microm diameter pulmonary
      artery. The results showed that verapamil, staurosporine and amiloride could
      notably block hypoxia-induced increase 3H-TdR incorporation and cell number.
      CONCLUSION: Proliferation of pulmonary artery smooth muscle cell responded to
      hypoxia differently according to the artery size; activation of calcium channel,
      PKC and Na(+)-H+ exchange might mediate the proliferation initiated by hypoxia.

PMID- 21171446
TI  - [Study on the relationship of metallothionein and antioxidases in protective
      mechanism of cardiomyocytes].
AB  - AIM: To study the relationship of Metallothionein (MT) and antioxidases in
      hypoxia/reoxygenation (H/R) and hypoxic preconditioning (HPC). METHODS: H/R and
      HPC model of rat cultured cardiomyocytes were established. Then the contents of
      MT and relevant changes of activities of antioxidases (SOD, CAT, GSHpx) of
      cardiomyocytes were determined while pretreated with the treatment: HPC. Zn2+
      inducing MT or MT antibody. RESULTS: In HPC and Zn2+ induced groups, all the
      contents of MT and the activities of antioxidases were obviously higher than
      those in H/R (P < 0.05, P < 0.01 respectively). While using MT, the activities of
      SOD were progressively increased than control (P < 0.05), CAT and GSHpx
      activities were lower than control (P < 0.01), but were significantly higher than
      those in I/R group (P < 0.01). In MT antibody groups, the activities of
      antioxidase were decreased extremely. CONCLUSION: MT has effects on the
      cardiomyocytes protective role of HPC. And can afford more capacity for
      cardiomyocytes to tolerate the H/R damage by the mechanism of increasing the
      activities of antioxidase.

PMID- 21171447
TI  - [The effect of aldosterone of promotion on proliferation of ventricular
      fibroblasts].
AB  - AIM: To study the effect of promoting aldosterone on proliferation of ventricular
      fibroblasts. METHODS: Assay of [3H]-TdR incorporation rate and RT-PCR were used.
      RESULTS: Aldosterone could promote [3H]-TdR incorporation of ventricular
      fibroblasts, the effective dose of aldosterone was among (1 x 10(-9)-1 x 10(
      6))mol/L, and had dose-dependent manner, the c-fos gene was expressed after
      stimulated by aldosterone for 15 min, and studied the highest in 1 h, then
      reduced later. Spironolactone, aldosterone receptor antagonist could block the
      effect of aldosterone. CONCLUSION: Aldosterone promotes the proliferation of
      ventricular fibroblasts, mediated by aldosterone receptor.

PMID- 21171448
TI  - [The transfection and expression of retro viral-mediated human FL cDNA in bone
      marrow stromal cell line].
AB  - AIM: The expression of retroviral-mediated FL gene transfer into bone marrow
      stromal cell line HFCL was studied. METHODS: FLT3 ligand (FL) cDNA was recombined
      with retroviral vector pLXSN by gene recombination technology. The recombinant
      plasmid was transferred into retrovirus packaging cell line PA3 17 by
      lipofectamine, and the resistant clones were selected by G418 selective medium.
      The mRNA expression in HFCL cells and integration of genome DNA were assayed by
      RT-PCR and genomic DNA PCR. The biological activity of FL in the culture was
      investigated by mouse bone marrow CFU-GM assay. RESULTS: The recombinant plasmid
      pLFSN was successfully constructed. The expression of FL mRNA was detected in
      HFCL cells. In the genome of these infected target cells, neo gene and FL cDNA
      were successfully expressed. The biological activity of FL in the culture
      demonstrated that HFCL cells transfected with FL could significantly augment FL
      in vitro. CONCLUSION: These results suggest that bone marrow stromal cell lines
      might become target cells of gene therapy.

PMID- 21171449
TI  - [Changes of the certain functions of mitochondria induced by acute exercise and
      the protective effect of bilirubin].
AB  - AIM: To study the mechanism of fatigue induced by acute exercise and the
      protective effect of bilirubin. METHODS: 41 Wistar male rats were divided into
      five groups: control group, exercise group, exercise recovery group, bilirubin
      treated exercise group and bilirubin-treated exercise recovery group. The rats
      were administrated with 1 micromol/kg body weight of bilirubin or saline once
      every day for 4 weeks, after swimming with load for 2 h, all of the rats were
      killed and several index were determined. RESULTS: Acute exercise could induce
      the increase of Ca2+ content in cytoplasm and mitochondria of gastrocnemius, Ca2+
      content increased continuously after 12 hours in mitochondria. The Ca2(+)-Mg2(+)
      ATPase activity decreased obviously after acute exercise, and the activity
      increased again after 12 hours. Bilirubin could inhibit these changes. The change
      of Mg2(+)-ATPase activity in mitochondria had little difference between bilirubin
      treated and untreated groups, both of which were lower than that of control
      group, but the recovery was faster in the bilirubin-treated group than that in
      untreated group. CONCLUSION: Bilirubin could protect muscle fibers from injury
      induced by acute exercise and delay the development of fatigue and promote the
      recovery through inhibiting the disturbance of the certain function of
      mitochondria.

PMID- 21171450
TI  - [Effect of dynorphin A1-13 on C6 glioma cells swelling induced by glutamate].
AB  - AIM AND METHOD: To explore the cell mechanism of brain edema and the effect of
      dynorphin A1-13 on swelling of C6 glioma cells. Water content of cell are studied
      by using 3-O-methyl-D-glucose. RESULTS: (1) Glutamate (0.5, 1.0, 10.0 mmol/L)
      increased the water content of C6 glioma at an hour. (2) Dynorphin A1-13 could
      significantly decrease the increasing in water content of C6 glioma cells induced
      by glutamate. (3) nor-BNI, a antagonist, could inhibit the effect of dynorphin A1
      13 on water content of swelling C6 glioma cells. CONCLUSION: Glutamate could
      induce the swelling of C6 glioma cells. Dynorphin A1-13 could reduce C6 glioma
      cells swelling induced by glutamate via kappa opioid receptor.

PMID- 21171452
TI  - [Study on the effect of hyperbaric oxygen on apoptosis in the CA1 region of
      hippocampus following forebrain ischemia reperfusion].
AB  - AIM AND METHODS: To study the mechanism of hyperbaric oxygen (HBO) on the
      treatment of cerebral ischemia, and to provide theoretical basis for hyperbaric
      oxygen treatment (HBOT), we examined the effect of 0.15 MPa and 0.25 MPa HBO
      treatment (60 min/d, for 3 successive days ) on ischemia reperfusion - induced
      apoptosis in gerbil hippocampus CA1 using TUNEL staining method. RESULTS: The
      number of neuronal apoptosis in hippocampus CA1 was significantly decreased in
      HBOT groups(P < 0.01). Neuronal apoptosis in hippocampus CA1 in 0.25 MPa groups
      were less than that in 0.15 MPa groups (P < 0.01). CONCLUSION: HBOT is effective
      in reducing neuronal apoptosis and in protecting neurons from injury of ischemia
      reperfusion, and 0.25 MPa is an appropriate pressure for HBOT.

PMID- 21171451
TI  - [Experimental research on permeability injury of pulmonary microvascular
      endothelial cells monolayer induced by tumor necrosis factor].
AB  - AIM AND METHODS: To investigate the mechanism of tumor necrosis factor (TNF)
      induced permeability injury of rat pulmonary microvascular endothelial cells
      (RPMVEC) monolayer, the effect of TNF on permeability of RPMVEC monolayer was
      examined with microfilter and the effect of TNF on RPMVEC F-actin was observed
      with immunocytochemistry. The interfering action of formoterol, anisodamine and
      cholera toxin on permeability and F-actin changes induced by TNF was also
      observed. RESULTS: (1) TNF induced significant increase in permeability of RPMVEC
      monolayer 30, 60 and 90 minutes after treatment with TNF. (2) F-actin in RPMVEC
      depolymerized 90 minutes after treatment with TNF. Permeability and F-actin did
      not change significantly when formoterol, anisodamine or cholera toxin was added
      separately. CONCLUSION: TNF can induce permeability injury of RPMVEC monolayer,
      which is correlated with depolymerization of F-actin. Formoterol, anisodamine and
      cholera toxin can inhibit the permeability change induced by TNF which may due to
      their inhibition to the distribution change of F-actin.

PMID- 21171453
TI  - [Preliminary study of analgesic mechanism of Buthus martensii Karsch (BmK) venom
      on central nervous system].
AB  - AIM: To investigate whether or not the lateral septal nucleus (LS) was one of
      important analgesic areas of BmK venom in the central nervous system (CNS), and,
      targeting on which receptor, analgesic effect was produced by it. METHODS: Pain
      threshold of skin was observed by the latent period of tail flick evoked by
      radiant heat. Glass micropipette placed in Pf was used to record unit discharges
      of neurons in it, before and after 0.01% BmK venom were injected into LS.
      Stainless steel cannula placed in the lateral cerebral ventricle (icy) and LS was
      used for microinjection. RESULTS: After injection of 2 microl 0.01% BmK venom
      into icy of rat, the pain threshold was apparently raised, which was completely
      returned by injection of 0.5 microl 0.25% naloxone into icy. After 0.5 microl
      0.01% BmK venom was injected into LS, 71% (15/21) nociceptive-on neurons and
      83.3% (5/6) nociceptive-off neurons decreased the nociceptive response to tail
      pinch, but no evident effect was observed in the non-nociceptive neurons.
      CONCLUSION: The analgesic effect of BmK venom was probably realized mainly by the
      opiate receptor, and LS was one of important analgesic areas of BmK venom on CNS.

PMID- 21171454
TI  - [Antinociceptive effect of allografted adrenal medulla into the spinal
      subarachnoid space in rats].

PMID- 21171455
TI  - [Effect of injectio Salvia Miltiorrhiza on gentamicin ototoxicity-induced
      activity of nitric oxide synthase in cochlear stria vascularis of guinea pig].
AB  - AIM: to investigate the change of nitric oxide synthase (NOS) activity in
      cochlear stria vascularis (SV) of guinea pig after gentamicin (GM) and Salvia
      Miltiorrhiza (SM) injection, and to explore the protective role of injectio SM on
      GM ototoxicity. METHODS: NADPH-diaphorase histochemistry staining and image
      quantitative analysis technique, combined with auditory brainstem response (ABR)
      measurement. RESULTS: SM + GM significantly reduced NOS activity in cochlear SV
      and ABR threshold as compared with CM along (P < 0.01); and ABR threshold shift
      was in high correlation with NOS activity (rControl = -0.9464; rGM = -0.9117; rSM
      + GM = -0.8958; P < 0.01). CONCLUSION: SM can reduce NOS activity in cochlear SV
      so as to alleviate GM ototoxicity, thus ameliorate hearing function.

PMID- 21171456
TI  - [Study of the growth and secretion of microencapsulated pancreatic B cell line in
      vitro].
AB  - AIM: To study the growth and secretion of pancreatic B cell line BTC6-F7 in the
      alginate polylysine-alginate (APA) microcapsules and explore the possibility of
      utilizing it as bioartificial islets. METHODS: Microencapsulated BTC6-F7 cells
      prepared with electric droplet generator were cultured in vitro, and the growth
      and insulin secretion of them were measured periodically. RESULTS: Over the 90
      day observation period, BTC6-F7 cells were able to grow and survive as cell
      clusters in the microcapsules and finally fulfill the capsules. But the
      microcapsules remained well after the long-time culture. The average total cell
      number per capsule were increasing with time, but the cell viability was
      decreasing. The changes of insulin secretion and average live cell number per
      capsule were in a same manner: for the first two weeks they increased rapidly and
      then maintained in a relatively constant levels for the rest time. CONCLUSION:
      The microencapsulated pancreatic B cells prepared by us could survive, grow and
      secretion for a long time. This has made a basis for further development of
      bioartificial islets, and also can be used to study the mechanism and therapy of
      diabetes mellitus.

PMID- 21171457
TI  - [Measurement of rat myocardial mitochondria permeability transition with
      spectrophotometer].
AB  - AIM: Mitochondrial permeability transition (MPT) is an important index to
      indicate the integrity and function of mitochondria. The principle of measurement
      for MPT is to observe the change of absorbance at 540 nm, due to the swelling of
      mitochondria by the disturbance of permeability transition of mitochondrial
      membrane when MPT increase. Consulting the literature and according to the
      reality in our laboratory, we established a spectrophotometric method for
      measuring myocardial MPT by using UV-240 spectrophotometer. METHODS: The decrease
      of absorbance and the time to equilibrium deltaA/min indicates the change of MPT.
      RESULTS AND CONCLUSION: The results showed that the optimal pH, concentration of
      protein and temperature for measuring MPT in our laboratory are pH 7.4, 0.5 mg
      protein/ml of mitochondria and 25 degrees C respectively.

PMID- 21171458
TI  - [Outward potassium currents in outer hair cells isolated from the cochlea of the
      guinea pig].

PMID- 21171459
TI  - [c-Fos expression of left ventricular experimental ventricular hypertrophy rats
      and the effect of cap on it].

PMID- 21171460
TI  - [Administration and evaluation nutrition support of live related intestinal
      transplantation during perioperation].

PMID- 21171461
TI  - [Progressively deformed fingers. How long will these hands still be functional?].

PMID- 21171462
TI  - [Assessment of the main gastrointestinal symptoms. Signals from the lower
      abdomen].

PMID- 21171463
TI  - [Sinobronchial syndrome. What can conventional medicine and what can naturopathy
      accomplish?].

PMID- 21171464
TI  - [The most important changes for family practice. New guidelines for atrial
      fibrillation].

PMID- 21171465
TI  - [Naturopathy consultation. Inflammatory and bacterial skin diseases].

PMID- 21171466
TI  - [Acute aortic dissection: be aware of signs and symptoms].
AB  - Acute aortic dissection is a rare medical emergency accompanied by high
      mortality. For ensuring fast diagnosis and delivery of appropriate medical
      treatment the knowledge of signs and symptoms is crucial. Here we summarize
      clinical presentation according to existing studies, focus on diagnosis and
      introduce to contemporary treatment of this disease.

PMID- 21171467
TI  - [Cementless hip replacement: indications, postoperative treatment, sports].

PMID- 21171468
TI  - [Cervical cancer--minimally invasive treatment].

PMID- 21171469
TI  - [Cerebral hypoxia or cyanide intoxication?].

PMID- 21171470
TI  - [Emergency checklist: acute tonsillitis].

PMID- 21171471
TI  - [Overweight and headache].

PMID- 21171472
TI  - [Effectiveness confirmed in studies. Intestine selective antibiotic reduces
      irritable bowel syndrome effectively].

PMID- 21171473
TI  - [Intrauterine adhesions--Asherman's syndrome].
AB  - Intrauterine adhesions known as Asherman's syndrome evolve after trauma to the
      basal layer of the endometrium usually secondary to curettage of a recently
      pregnant uterus. The lesions range from minor to severe cohesive adhesions that
      affect menstrual function and fertility. Operative hysteroscopy is the mainstay
      of diagnosis, classification and treatment of the intrauterine adhesions.
      Significantly obliterated cavity may require multiple hysteroscopic adhesiolysis
      to achieve a satisfactory anatomical and functional result. Operative
      hysteroscopy for selective curettage of residual trophoblastic tissue instead of
      nonselective conventional curettage may prevent intrauterine adhesions.

PMID- 21171474
TI  - [Dysplastic melanocytic nevus].
AB  - The dysplastic melanocytic nevus remains an issue of controversy despite
      extensive investigations. On clinical grounds the term atypical melanocytic nevus
      should be used, while dysplastic melanocytic nevus describes histological
      characteristics. The association with melanoma is complex. With the clinical
      picture, dermatoscopy and molecular biological or genetic examinations one can
      often not distinguish a histological dysplastic nevus from a melanoma. In
      patients with large amounts of melanocytic nevi it is important to assess the
      total melanoma risk, the need for patient surveillance and motivate the patient
      for self-examination. In high-risk patients the amount of benign melanocytic nevi
      is increased and many clinically atypical and microscopically dysplastic nevi can
      be found. The relatives of these patients should also be examined. Because of the
      rising incidence of melanoma and the lack of therapeutic options in disseminated
      disease, the surveillance of high risk patients, the early detection of melanoma
      and excision play a key role in patient management.

PMID- 21171475
TI  - [The effects of antidepressive drugs among the patients with memory disturbances-
      a systematic review].
AB  - The aim was to provide a systematic review of the effects of antidepressive drugs
      on depression among the aged with memory disturbances or dementia. Randomized,
      controlled trials (RCT) published in 1980-2009 were searched in Medline (PubMed)
      and Cochrane databases. The material consisted of 11 original RCT's. Depressive
      symptoms declined in many studies both in the active drug group and in the
      placebo group. Only four trials showed a statistically significant difference
      between an active drug and a placebo in decreasing depressive symptoms.
      Psychosocial support was arranged in all trials, which may explain the positive
      effects of placebo and gives support to the conclusion about the importance of
      psychosocial treatment of depression. Antidepressive drugs may be effective in
      treating major depression among the aged suffering from memory disturbances or
      dementia, but more studies are needed. The side effects of tricyclic
      antidepressants are problematic in the aged, and they should not be prescribed.

PMID- 21171476
TI  - [Botulinum toxin useful in urological problems].
AB  - Urological and gastroenterological patients may benefit from the therapeutic use
      of botulinum neurotoxin. Urologic indications include overactive bladder
      refractory to conventional treatments, painful bladder, chronic pelvic pain
      syndromes and problems with bladder emptying. Currently, there are no approved
      therapeutic indications for urologic conditions. In general, botulinum neurotoxin
      treatment is well tolerated and adverse events are predictable and limited to the
      urogenital tract, though rare severe and fatal complications have been reported.

PMID- 21171477
TI  - [Swollen lip and cobblestone-like stomatitis in a young person--due to orofacial
      granulomatosis].
AB  - Chronic granulomatous inflammation of the mouth and the lip region is an
      increasing problem. Almost every second person with the disease will develop
      chronic bowel inflammation, thus exclusion of bowel inflammation by fecal testing
      is recommended. Topical tacrolimus or orally administered glucocorticoids,
      antibiotics and immunosuppressive drugs have been used in the treatment. The
      symptoms are typically variable, and visible changes to same extent persist for
      years. Diet has been suspected as the triggering factor, and some patients have
      benefited from benzoate and cinnamon-free diet.

PMID- 21171478
TI  - [Update on current care guidelines: cataract in adults].
AB  - The indications for cataract surgery under the Finnish public healthcare system
      are as follows: a BCVA in the better eye of < or = 0.5, or a BCVA in the worse
      eye of < or = 0.3. A small, clear corneal incision is the most commonly
      administered type of cataract wound. This entails decreased postoperative
      inflammation and surgically induced astigmatism. Sharp-edged IOL optics decreases
      the incidence of secondary cataracts. Povidone-iodine preoperatively, and
      intracameral cefuroxime, reduce the incidence of postoperative endophthalmitis.
      Pre- and postoperative topical antibiotics are widely used, despite a lack of
      clear evidence on their effectiveness.

PMID- 21171479
TI  - What is the relevance of the term "functional" in psychiatric disorders in the
      era of functional brain imaging?

PMID- 21171480
TI  - Is disturbed sleep a clinically useful marker to determine the suicide risk in
      patients with posttraumatic stress disorder?

PMID- 21171481
TI  - Affective disorder and polycythaemia vera.

PMID- 21171482
TI  - Potential of sucrose-induced analgesia to relieve pain in male adults: a
      preliminary study.
AB  - AIM: Sucrose-induced analgesia frequently has been investigated for pain relief
      during invasive procedures in neonates. This analgesic mechanism is thought to be
      mediated by the endogenous opioid system, taking advantage of sweet taste.
      However, few studies have examined the effects of sucrose-induced analgesia in
      adults. Therefore, this preliminary study examines the analgesic efficacy of a
      sucrose stimulus on experimentally induced pain in male adults. METHODS: A
      randomized, single-masked, cross-over study was conducted to examine the
      analgesic effect of a sucrose stimulus in male adults. Experimental pain was
      induced with the cold pressor test. Prior to and during the cold pressor test,
      the participants held either a 24% sucrose solution or distilled water as a
      control in their mouth. The analgesic efficacy was evaluated by using the pain
      threshold, pain tolerance, Profile of Mood State, and two visual analogue scales
      of pain intensity and taste pleasantness. RESULTS: The sucrose stimulus reduced
      the pain response of the participants. The mean threshold increased significantly
      when using the 24% sucrose solution, compared with distilled water. The mean
      tolerance also increased under the sucrose condition. In addition, the taste
      pleasantness score was significantly higher under the sucrose condition than with
      distilled water. However, neither condition showed a significant difference in
      the scores of the visual analogue scales for pain. CONCLUSIONS: These findings
      suggest that sucrose stimuli might induce the antinociceptive effects on pain in
      male adults. More trials are needed to further elucidate these effects before
      this analgesic method can be used for clinical pain in adults.

PMID- 21171483
TI  - A man of letters: Why was the morning paper suddenly in a foreign language?

PMID- 21171484
TI  - Drinking games: how much people drink may matter less than how they drink it.

PMID- 21171485
TI  - Schedules of controlled substances: placement of 5-methoxy-N,N-dimethyltryptamine
      into Schedule I of the Controlled Substances Act. Final rule.
AB  - With the issuance of this final rule, the Deputy Administrator of the Drug
      Enforcement Administration (DEA) places the substance 5-methoxy-N,N
      dimethyltryptamine (5-MeO-DMT), including its salts, isomers and salts of isomers
      whenever the existence of such salts, isomers, and salts of isomers is possible,
      into schedule I of the Controlled Substances Act (CSA). This action by the DEA
      Deputy Administrator is based on a scheduling recommendation from the Assistant
      Secretary for Health of the Department of Health and Human Services (DHHS) and a
      DEA review indicating that 5-MeO-DMT meets the criteria for placement in schedule
      I of the CSA. This final rule will impose the criminal sanctions and regulatory
      controls of schedule I substances under the CSA on the manufacture, distribution,
      dispensing, importation, exportation, and possession of 5-MeO-DMT.

PMID- 21171486
TI  - Health promotion F.I.R.S.T.: introducing the legislation.

PMID- 21171487
TI  - [Housing price formation in 17th-century Venice].

PMID- 21171489
TI  - Gender equity, focus on high-risk reduction and the future of health promotion.
      The new gender gap.

PMID- 21171490
TI  - Healthcare and the worst economic nightmare.

PMID- 21171491
TI  - Volatile economic times and financial markets turmoil have significantly affected
      virtually all healthcare providers.

PMID- 21171492
TI  - The challenge of environmental sustainability in healthcare.

PMID- 21171493
TI  - Ask us. White spot lesions: prevention and treatment.

PMID- 21171494
TI  - Commentary. An alternative approach to the transitional rehabilitation of infra
      occluded primary second molars.

PMID- 21171495
TI  - Commentary. Irradiance differences i n the violet (405 nm) and blue (460 nm)
      spectral ranges among dental light-curing units.

PMID- 21171496
TI  - Commentary. Assessment of color parameters of composite resin shade guides using
      digital imaging versus colorimeter.

PMID- 21171497
TI  - Commentary. Influence of bleaching agents on surface roughness of sound or eroded
      dental enamel specimens.

PMID- 21171498
TI  - Commentary. Effect of sali va contamination and cleansing solutions on the bond
      strengths of self-etch adhesives to dentin.

PMID- 21171499
TI  - Self-adhesive resin cements.

PMID- 21171500
TI  - A new vision, a new plan.

PMID- 21171501
TI  - Introduction of Health Promotion FIRST (funding integrated research synthesis and
      training) in the United States Senate.

PMID- 21171502
TI  - Social entrepreneurs.

PMID- 21171503
TI  - Health promotion on a global scale: Oxford Vision 2020.

PMID- 21171504
TI  - Sir Richard Dole: The passing of a remarkable scientist and the completion of a
      remarkable study.

PMID- 21171505
TI  - [The French Revolution and the rural economy].

PMID- 21171506
TI  - [Household life cycles and the Russian labor market,  1861-1922].

PMID- 21171507
TI  - $1 billion a week for global well-being.

PMID- 21171508
TI  - Measuring the structure of visual fields in nursing units.

PMID- 21171509
TI  - WHO classification of tumours of haematopoietic and lymphoid tissues in 2008: an
      overview.

PMID- 21171510
TI  - Squamous cell carcinoma arising in epidermal and human papillomavirus associated
      cysts: report of three cases.
AB  - OBJECTIVES: The clinical-pathological features of squamous cell carcinoma (SCC)
      arising in cutaneous cysts has been studied. METHODS: We report two cases of SCC
      arising in epidermal cyst (EC) and one case in human papilloma virus associated
      cyst (HPAC). RESULTS: In the first EC case, a 88-year-old man presented a cystic
      right zigomatic mass. Histopathology revealed a cyst lined by stratified squamous
      epithelium in continuity with invasive keratinizing SCC. In the second EC case, a
      96-year-old man presented with a 1.5 x 1 cm nodular lesion localized at the helix
      of the right ear. Histopathology showed the typical cystic wall of an EC with
      transition to invasive keratinizing SCC. Finally, a 86 year-old woman presented
      with a perineal cystic nodule 1.5 cm in diameter. The wall showed varying degrees
      of papillomatosis, hypergranulosis, parakeratosis with dysplastic and koilocytic
      changes. Areas of in situ and invasive SCC were found. Human papillomavirus (HPV)
      16 was detected. CONCLUSIONS: SCC arising in an EC may be diagnosed only with the
      support of an accurate histopathological documentation in order to exclude
      mimics. Regarding HPAC, the site, the malignant transformation and the finding of
      HPV 16 type, may be considered features of an extraordinary rare case.

PMID- 21171512
TI  - Risk management: correct patient and specimen identification in a surgical
      pathology laboratory. The experience of Infermi Hospital, Rimini, Italy.
AB  - Because of its complex nature, surgical pathology practice is prone to error. In
      this report, we describe our methods for reducing error as much as possible
      during the pre-analytical and analytical phases. This was achieved by revising
      procedures, and by using computer technology and automation. Most mistakes are
      the result of human error in the identification and matching of patient and
      samples. To avoid faulty data interpretation, we employed a new comprehensive
      computer system that acquires all patient ID information directly from the
      hospital's database with a remote order entry; it also provides label and request
      forms via-Web where clinical information is required before sending the sample.
      Both patient and sample are identified directly and immediately at the site where
      the surgical procedures are performed. Barcode technology is used to input
      information at every step and automation is used for sample blocks and slides to
      avoid errors that occur when information is recorded or transferred by hand.
      Quality control checks occur at every step of the process to ensure that none of
      the steps are left to chance and that no phase is dependent on a single operator.
      The system also provides statistical analysis of errors so that new strategies
      can be implemented to avoid repetition. In addition, the staff receives frequent
      training on avoiding errors and new developments. The results have been shown
      promising results with a very low error rate (0.27%). None of these compromised
      patient health and all errors were detected before the release of the diagnosis
      report.

PMID- 21171511
TI  - A 3-D study of capsular invasion in follicular thyroid tumors. A novel approach
      to an old dilemma.
AB  - OBJECTIVE: The diagnosis of follicular tumors of the thyroid mainly rests on the
      examination of peri-lesional capsule. Lesions with an intact shell are labeled as
      adenoma, those with capsular invasion are considered carcinoma and those with
      doubtful aspects are regarded as tumors of uncertain malignant potential. AIM: To
      better understand the biology of capsular invasion and its practical implication
      by applying a peculiar three dimension (3-D) reconstruction. METHOD: Two
      follicular carcinoma (FC) and one follicular tumour of uncertain malignant
      potential (FT-UMP) were considered. Areas of true/doubtful capsular invasion were
      labeled using Tissue Micro Array technology and the corresponding paraffin blocks
      underwent serial sectioning. H&E slides (range 30-100, mean 70) were captured as
      pictures, aligned using automated method based on the maximization of mutual
      information and imported into a 3-D image processing software (AMIRA). RESULTS:
      The 3-D reconstruction revealed that capsular openings were oval shaped and sized
      approximately equal to 100-200 microm. In one FC the hole was entirely engaged by
      a tumor mass. In the remaining cases (1 FC and 1 FT-UMP) the 3-D reconstruction
      showed a small feeding vessel (approximately equal to 50 micro) passing through
      the capsule together with the bulge of the lesion [see 3-D reconstruction at
      http://www.ibfm. cnr.it/ricerca/inv_cap.php]. CONCLUSIONS: Our approach allows a
      better spatial reconstruction of the exact point of capsular interruption; the
      results obtained suggest that capsular invasion can be due either by abruptly
      interruption of the shell or by a protrusion along the path of a small feeding
      vessel.

PMID- 21171513
TI  - Ectopic thyroid of the lung. An additional case.
AB  - Thyroid ectopy is a rare phenomenon, which usually occurs in the cervical
      midline. We, herein, illustrate an unusual location of thyroid tissue,
      incidentally found at autopsy within the lung of a 77-year old male.

PMID- 21171514
TI  - Primary sarcoidosis of the breast: case description and review of the literature.
AB  - Sarcoidosis is a systemic granulomatous disease of unknown aetiology. The breast
      is involved in less than 1% of cases. Breast can be either a primary or a
      secondary site of presentation. Breast sarcoidosis often mimics carcinomas at
      clinical examination. We report a case of breast sarcoidosis detected during
      screening mammography in a 57-year-old woman. The lesion presented as a 1.4 cm
      nodule located in the right breast. On histology, it was characterized by non
      caseating giant cell granulomas. Differential diagnoses included idiopathic
      granulomatous mastitis, tuberculosis, fungal infection, cat-scratch disease and
      sarcoid-like reactions to cancer. Further clinical and laboratory investigations
      were consistent with a diagnosis of sarcoidosis. Specifically, serum levels of
      angiotensin-converting enzyme (ACE) were elevated and a CT scan showed small
      bilateral pulmonary nodules distributed along the pleura and bronchovascular
      bundles (perilymphatic pattern), as well as enlarged bilateral hilar and
      mediastinal lymph nodes. The patient received corticosteroid treatment, and is
      presently asymptomatic. Breast involvement by sarcoidosis, although rare, should
      be considered when dealing with granulomatous lesions of the breast.

PMID- 21171515
TI  - Lipoblast-like signet-ring cells in neurofibroma: a potential diagnostic pitfall
      of malignancy.
AB  - Benign peripheral nerve sheath tumours, including neurofibroma, may occasionally
      contain a heterologous mature fatty component. Additional lipoblast-like cells
      can be occasionally identified among mature adipocytes. We report the first case
      of a plexiform neurofibroma from a NF1 patient containing exclusively lipoblast
      like cells exhibiting morphological and immunohistochemical features identical to
      univaculoted lipoblasts typically seen in myxoid liposarcoma. Awareness of the
      possibility that an otherwise typical neurofibroma may contain lipoblast-like
      cells is crucial for the pathologist to avoid a misdiagnosis of malignancy.
      Differential diagnostic problems and histogenetic considerations are provided.

PMID- 21171516
TI  - Report of a case of epithelioid hemangioendothelioma of the anterior mediastinum
      metastatic to pleura.
AB  - We present a case of epithelioid hemangioendothelioma metastatic to pleura, in a
      69-year-old woman with chest pain. This distinctive vascular neoplasm can arise
      in various organs, most commonly in middle-aged women. It is characterized by
      slow growth, and, microscopically, by epithelioid tumor cells in appearance.
      Epithelioid hemangioendothelioma should be distinguished mainly from primary or
      metastatic carcinomas and angiosarcoma. Definitive diagnosis often requires
      immunohistochemistry. Its clinical course is unpredictable, although survival
      rates are better than for angiosarcoma.

PMID- 21171517
TI  - Atypical dermatofibroma with predominant epithelioid/deciduoid-like cell
      component. Histogenetic considerations in the wide spectrum of fibrohistiocytic
      dermal tumours.
AB  - Atypical and epithelioid cell variants of dermatofibroma may represent a
      potential diagnostic pitfall. Only rarely atypical dermatofibroma may show focal
      epithelioid cell features. We herein report a rare case of dermatofibroma
      composed of a predominant (> 90%) epithelioid/deciduoid-like cell component, in
      which rare multinucleated bizarre cells and atypical mitoses were additional
      findings. Tumour was classified as "atypical dermatofibroma with predominant
      epithelioid/deciduoid-like cell component". The coexistence of at least two
      different variants, i.e. epithelioid and atypical variants, in the same
      dermatofibroma suggests that dermal fibrohistiocytic tumours belong to a
      continuous morphological spectrum. Accordingly, the morphological variants of
      dermatofibroma should be regarded as variations on a common basic theme.
      Differential diagnosis with other epitheliod cell dermal tumour- and tumour-like
      lesions is discussed.

PMID- 21171518
TI  - Recommendations for mutational analysis of EGFR in lung carcinoma.

PMID- 21171519
TI  - Minimally-invasive surgery in paediatric oncology: proposal of recommendations.
AB  - The Authors report a proposal of recommendations concerning Minimally Invasive
      Surgery (MIS) in Paediatric Oncology. Since the exact role of MIS in Paediatric
      Oncology is still not completely defined, a restrict panel of Italian Paediatric
      Surgeons, some interested in Oncologic Surgery, others in MIS, prepared a
      schematic document, mainly founded on literature data, to provide Paediatric
      Surgeons with recommendations useful to approach paediatric tumours with MIS. The
      final draft was approved by the Italian Group of Paediatric Oncologic Surgeons.
      The Authors summarize the feasibility of MIS, when performed with different
      purposes (biopsy / resection) and timing (initial / delayed surgery) for the most
      common solid tumours in children. The oncologic criteria must be always followed
      with MIS as well as with "open" surgery.

PMID- 21171520
TI  - Counseling and informed consent: the experience in a pediatric cardiology unit.
      How to communicate a pathological diagnosis.
AB  - The aim of our study was to create an operative scheme for conveying a
      pathological diagnosis with emphasis on communication strategies. In order to
      check the validity of the scheme, parents of 122 of our patients were contacted
      by an outside observer and were asked to answer anonymously to a questionnaire
      concerning their experience in our unit. The questionnaire has been structured in
      three parts in order to verify (1) the quality of the communication of the
      diagnosis, (2) the team-patient relationship and (3) the comparison between our
      unit and the others. 87% of parents declared the language used in the
      communication clear and comprehensible and the time dedicated to the explanations
      sufficient (p<.01). They judged the quality of the information received as
      excellent (50%) or good (50%) (p<.01). Eightyfour % of them thought that the
      information given was sufficient and there was no need for any more details
      (p<.01). 92% perceived a comfortable atmosphere, they felt involved in the
      communication and encouraged to ask questions (p<.01). 91% described the
      behaviour of the team as helpful and warm without differences between the
      different figures of the unit (p<.01). In regard to the psychological support 70%
      of parents found it essential, 30% found it very useful (p<.05). These results
      show that our operative scheme is functional to the communication and to the team
      patient relationship. It permits an "informed consent" as an aware choice of the
      parents and consequently a better way of management of the congenital heart
      disease.

PMID- 21171521
TI  - Thrombosed aneurysm of ductus arteriosus: a case report.
AB  - Spontaneous aneurysms of the ductus arteriosus are rare complications of a patent
      ductus arteriosus. It is met at any age but it is most commonly seen in children
      under two months of age. Echocardiography is the best test to diagnose a ductus
      arteriosus, but actually the role of thoracoscopy is to help in differential
      diagnosis of mediastinal masses. Surgery should be recommended without delay, to
      avoid fatal complications, with the resection of the thrombosed aneurysm of the
      ductus arteriosus.

PMID- 21171522
TI  - An unusual case of asymptomatic appendicular cutting foreign body.
AB  - Foreign body ingestion is a common problem in pediatric age. Foreign bodies in
      the lumen of appendix is a well known event. In this condition perforation or
      appendicitis may occur even for blunt or sharp objects. For these reasons, in
      case of stasis of foreign body in the lumen of appendix a prophylactic
      appendectomy is recommended. A case of asymptomatic ingested cutting foreign body
      in the appendix is presented and the approach is discussed according to the
      literature data.

PMID- 21171523
TI  - Comparative study on the actions of toxin extracts from two different puffer
      fishes on I(Na) and respiratory N-M transmission in the rat.
AB  - We performed a comparative study on the effects of toxin extracts prepared from
      muscle and liver of two different puffer fishes on voltage dependent sodium
      current (I(Na)), and compared the results with that of tetrodotoxin (TTX). The
      amount of toxin contained in the muscle or liver expressed as an amount of
      equipotent TTX differed in the two species (0.11-57.98 microg TTX/g tissue). In
      addition, we observed the effects of TTX or toxin extracts on the twitch
      contraction evoked by direct muscle stimulation of the rat hemidiaphragm or
      indirect phrenic nerve stimulations, in an attempt to understand the mechanisms
      involved in the transmission failure in the respiratory muscles, due to the
      ingestion of TTX bearing puffers, and found that TTX or toxin extracts
      preferentially affect motor nerve rather than muscle.

PMID- 21171524
TI  - The counter-regulation of atherogenesis: a role for interleukin-33.
AB  - The recently recognized cytokine interleukin-33 and its receptor ST2 play a
      favorable role during atherogenesis by inducing a Th1 --> Th2 shift of the immune
      response. IL-33 also protects the failing human heart from harmful biomechanical
      forces which lead to cardiomyocyte hypertrophy and exaggerated interstitial
      fibrosis. IL-33 inevitably displays side effects common to other Th2 cytokines,
      the most grave of which is a predisposition to allergic reactions. IL-33 is a
      nuclear transcription factor of endothelial cells. As such, it is abundant in
      nonproliferating vessels. Its down-regulation is required for angiogenesis, which
      may be profitable in wound healing or deleterious in tumor growth.

PMID- 21171525
TI  - The energetic and metabolic effect of Ringerfundin (B. Braun) infusion and
      comparison with Plasma-Lyte (Baxter) in healthy volunteers.
AB  - Measurement of parameters of energy requirement, respiratory quotient (RQ), rate
      of oxygen consumption (VO2) and rate of carbon dioxide production (VCO2) reveal
      Ringerfundin as an excellent and metabolically stable-acting balanced ionic
      solution, which does not increase the consumption of O2 or the total energy
      requirement. In conclusion, Ringerfundin was very well tolerated and in no case
      were observed undesirable effects.

PMID- 21171526
TI  - Visual functions after laser photocoagulation in central serous
      chorioretinopathy.
AB  - The authors evalute the visual functions of patients with unilateral central
      serous chorioretinopathy (CSC) and compare them with their non-affected eye and
      with a control group. Fourteen patients with CSC treated with direct laser
      photocoagulation were examined preoperatively and followed-up, up to 2 years
      postoperatively. Baseline best corrected visual acuity (BCVA) and contrast
      sensitivity (CS) of both eyes of patients was significantly lower in comparison
      with the controls. BCVA and CS in affected eyes were significantly lower compared
      to the fellow eye of patients. The final BCVA and CS of patients did not differ
      significantly from the controls, except CS of affected eyes in the spatial
      frequency of 3.69 c/deg. Two years after laser treatment, there were only
      nonsignificant differences of both photopic full-field electroretinography
      (phERG) and multifocal electroretinography (mfERG) responses between the treated,
      the nonaffected eye of the patients and the control group with exception of a
      significantly longer P1 implicit time in the parafoveolar region in affected
      eyes. Colour discrimination was normal in 85.8% of affected eyes of the patients.
      Despite a significant improvement of macular function in CSC eyes, functional
      examination methods do not prove complete resolution of function 2 years after
      laser-treatment.

PMID- 21171527
TI  - Effect of Ramadan fasting on tear proteins.
AB  - Muslims abstain from eating, drinking and smoking from dawn to sunset during the
      holy month of Ramadan. Prolonged fasting is thought to be among risk factors for
      many diseases, e.g., cardiovascular, gastrointestinal and various infectious
      diseases. It could also play a part in several eye diseases, including dry eye
      syndrome, glaucoma, and cataract. Toxic and oxidative effects due to increased
      concentrations of some biochemicals as a result of reduction in tear volume
      thought to play an important role in damaging ocular tissue. Human tear is an
      important biological fluid similar to blood in many aspects. Tear film is
      composed of three basic layers i.e. lipid, aqueous and mucin. The tear film
      covering the ocular surface presents a mechanical and antimicrobial barrier, and
      endures an optical refractive surface. The aim of this study was to analyze and
      compare tear protein of volunteers during fasting. Using two reliable analytical
      methods, i.e. electrophoresis and high performance liquid chromatography (HPLC),
      we compared tear protein content of sixty volunteers (35 males and 25 females, 23
      27 years old) during fasting in holly month of Ramadan (FAST: n = 62) and one
      month before Ramadan (CTRL: n = 60). The results showed that some identified tear
      proteins decreased during fasting. On the other hand, the activity of some
      enzymes such as lysozyme, lactoferrin and alpha amylase also decreased in fasting
      samples. Electrophoresis results showed that tear protein patterns in FAST (P <
      0.05) were different from those of CTRL. There were a few more protein peaks in
      the FAST group (P < 0.005) than in CTRL.

PMID- 21171528
TI  - Neutrophilic dermatosis of the dorsal hands associated with a "myeloproliferative
      neoplasm, unclassifiable" and a simultaneous cancer of colon.
AB  - Neutrophilic dermatosis of the dorsal hands is a variant of Sweet's syndrome. We
      herein describe an 83-year-old woman with a neutrophilic dermatosis of the dorsal
      hands associated with a "myeloproliferative neoplasm, unclassifiable" and a
      simultaneous cancer of colon. To our knowledge, and after a search in PubMed, the
      association of Sweet's syndrome with a "myeloproliferative neoplasm,
      unclassifiable" and a simultaneous cancer of colon has not previously been
      reported.

PMID- 21171529
TI  - Plasmapheresis-induced clinical improvement in a patient with steroid-resistant
      nephrotic syndrome due to podocin (NPHS2) gene mutation.
AB  - Podocin mutations (NPHS2 gene) are mostly responsible for steroid-resistant
      nephrotic syndrome (SRNS) of childhood onset. Patients with NPHS2 gene mutations
      do not respond to corticoids and other immunosuppressive agents; partial
      remission can be rarely induced by cyclosporin A. We present a boy, where SRNS
      was diagnosed within first year of life. By the age of 15 years, proteinuria
      reached 9000 mg/24 h, cholesterolemia 15 mmol/L, albuminemia 19.6 g/L, in spite
      of combined therapy with cyclosporine A, methylprednisolone, enalapril and
      losartan. At that time a combined heterozygous form of two NPHS2 gene mutations
      (p.R138Q and p.V290M) was diagnosed, methylprednisolone was discontinued and
      patient underwent ten plasmapheresis procedures. This resulted in clinical
      improvement (proteinuria 3000 mg/24 h, S-cholesterol 6 mmol/L, albumin 30g/L)
      lasting for three years. In conclusion, plasmapheresis can result in clinical
      improvement and stabilization of SRNS caused by podocine mutation, before renal
      replacement therapy is initiated.

PMID- 21171530
TI  - Five monoterpenes from leaves of Rhododendron anthopogon.
AB  - A phytochemical investigation of the leaves of Rhododendron anthopogon revealed
      the presence of five known monoterpenes: ranhuadujuanine A (1),
      cannabiorcicyclolic acid (2), ranhuadujuanine B (3), ranhuadujuanine C (4) and
      ranhuadujuanine D (5). All compounds are firstly reported as natural products.
      The assignments of some 13C-signals of ranhuadujuanine A reported in the
      literature were revised on the basis of 2D-NMR spectra.

PMID- 21171531
TI  - Health care reform and health disparities: implications for social workers.

PMID- 21171532
TI  - Health inequities: evaluation of two paradigms.
AB  - Social work practice in health is shaped by underlying paradigms.To effectively
      target health inequities, practitioners need to consider appropriate paradigms.
      In this exploration of how six health paradigms shape theory and practice, the
      two health paradigms that most attended to health inequalities are social
      determinants of health and political economy. The article undertakes a critical
      review of the social determinants of health paradigm and the political economy
      paradigm regarding how they might shape social work theory and practice targeting
      health inequities.

PMID- 21171533
TI  - Can racial disparity in health between black and white Americans be attributed to
      racial disparities in body weight and socioeconomic status?
AB  - Few studies have examined to what extent racial disparities in chronic health
      conditions (CHCs) are attributable to racial differences in body weight (measured
      as body mass index [BMI]) and socioeconomic status (SES) among older adults. To
      address this gap, using longitudinal data from the Health and Retirement Study,
      the current study examined risk factors of CHC trajectory including race, BMI,
      and SES. The sample consists of 22,560 in 1998, 20,825 in 2000, and 19,004 in
      2002. Data analysis was done through latent growth curve modeling. As expected,
      older adults presented an increasing trajectory of CHCs over time. Black
      Americans presented a significantly more negative CHC trajectory than did their
      white counterparts, confirming racial disparity in health over time. Consequent
      hierarchical analyses revealed that racial disparity in CHC trajectory can be
      explained by racial disparity in BMI and that racial disparity in BMI can be
      attributed to racial disparity in SES. Because low SES is closely related to
      unhealthy diet and negative health behaviors that may subsequently lead to
      obesity and chronic health conditions, the findings suggest that to address
      racial disparity in CHCs, it is important for social workers to continuously try
      to mitigate racial inequality in SES.

PMID- 21171534
TI  - Health insurance disparities among immigrants: are some legal immigrants more
      vulnerable than others?
AB  - This study examined health insurance disparities among recent immigrants. The
      authors analyzed all working-age adult immigrants between the ages of 18 and 64
      using the New Immigrant Survey data collected in 2003.This survey is a cross
      sectional interview of recent legal permanent residents on their social,
      economic, and health status. Respondents were interviewed in English or in their
      preferred languages. Nearly two-thirds of immigrants were uninsured, in spite of
      their strong labor force participation. Of the four key classes of immigration-
      employment based, family sponsored, refugee/asylum program, and diversity program
      -the diversity program immigrants were least likely to be insured, controlling
      for a wide array of demographic, human capital, acculturation, and assets-related
      variables. Strategies to increase health insurance coverage among legal
      immigrants, especially diversity immigrants, are discussed.

PMID- 21171535
TI  - Uncovering health care inequalities among adults with intellectual and
      developmental disabilities.
AB  - Even as attention is drawn to the increasing number of individuals who experience
      health inequalities in the United States, little is known about the health
      inequalities experienced by individuals with intellectual and developmental
      disabilities. Current disability research mainly focuses on physical
      disabilities. This article discusses the health disparities experienced by
      individuals with intellectual and developmental disabilities.The authors
      conducted focus groups with parents/guardians, self-advocates, and community
      support professionals and key informant interviews with health care professionals
      to assess the needs of this less frequently documented population. Results from
      this study indicate that individuals with intellectual and developmental
      disabilities face health care disparities and inequities in four areas: access,
      knowledge, communication, and quality.

PMID- 21171536
TI  - Child health inequality: framing a social work response.
AB  - Numerous studies acknowledge that the well-being of our nation hinges on the
      health of its people. There is specific concern about children because they
      represent the future. Ignoring children's health needs can compromise their
      educational preparedness, occupational pursuits, productivity, and longevity.
      Current science demonstrates that developmental, emotional, or behavioral
      limitations experienced during the early years of life and over the life course
      are associated with poor adult health outcomes. Poverty, restricted access to
      health insurance and health care services, cultural and linguistic barriers,
      neighborhood conditions, and racial and class inequalities exacerbate poor health
      outcomes and contribute to child health inequality. To respond to the
      complexities and threats of child health inequality, social workers must be
      sensitized to the physical and material constraints that support them and join
      forces with other disciplines in comprehensive approaches to reduce and prevent
      them. This article focuses on current knowledge about child health inequality and
      recommends how social workers can effect change in this area through practice,
      policy, and research that adheres to the profession's ethical principles and
      standards and promotes the public health.

PMID- 21171538
TI  - Social work and the social determinants of health perspective: a good fit.

PMID- 21171537
TI  - Using community-based participatory research to ameliorate cancer disparities.
AB  - Although much attention has been paid to health disparities in the past decades,
      interventions to ameliorate disparities have been largely unsuccessful. One
      reason is that the interventions have not been culturally tailored to the
      disparity populations whose problems they are meant to address. Community-engaged
      research has been successful in improving the outcomes of racial and ethnic
      minority groups and thus has great potential for decreasing between-group health
      disparities. In this article, the authors argue that a type of community-engaged
      research, community-based participatory research (CBPR), is particularly useful
      for social workers doing health disparities research because of its flexibility
      and degree of community engagement. After providing an overview of community
      research, the authors define the parameters of CBPR, using their own work in
      African American and white disparities in breast cancer mortality as an example
      of its application. Next, they outline the inherent challenges of CBPR to
      academic and community partnerships. The authors end with suggestions for
      developing and maintaining successful community and academic partnerships.

PMID- 21171539
TI  - How lucky am I to be awarded a CANO grant! One part luck, major part strategy.

PMID- 21171540
TI  - The supportive care needs of family members of men with advanced prostate cancer.
AB  - This exploratory study identified the supportive care needs of family members of
      men with advanced hormone-sensitive (HS) and hormone-refractory (HR) prostate
      cancer. In focus groups and individual interviews, we asked eight family members
      of men with HS disease and 11 family members of men with HR disease to identify
      their supportive care needs and recommend strategies for improving care to meet
      these needs. Unmet needs common to both groups were lack of information and
      uncertainty about the future. Unmet needs specific to family members affected by
      HR prostate cancer related to caregiver burden, practical assistance, and
      isolation. Implications for practice to improve supportive care services for
      families affected by APC are provided.

PMID- 21171541
TI  - Radical cystectomy for bladder cancer: a qualitative study of patient experiences
      and implications for practice.
AB  - Patients being treated for bladder cancer share issues in common with other
      cancer patients, but also experience issues that are unique to their surgical
      treatment. This study used a descriptive qualitative approach to explore the
      experiences of patients who had undergone radical cystectomy for bladder cancer
      Twenty-two participants were interviewed in-depth on one occasion and were
      invited to attend a focus group session following the analysis of the interview
      transcripts. Participants described the shock of their diagnosis, their lack of
      information about bladder cancer, the importance of clear communication with care
      providers, and the types of adjustments they had to make following surgery.
      Specifically, changes in bodily function, body image, sexual relationships, and
      intimacy presented challenges for these participants. Although there was a sense
      of acceptance about the treatment-related events, there were still significant
      adjustments required by individuals following their surgery. Information, open
      communication, and support from family and friends were seen as important factors
      in helping patients adjust after surgery. Patients require clear, concise and
      consistent information about their cancer, treatment options, and course of care.
      Nurses caring for patients following surgery for bladder cancer need to
      understand the unique needs of these patients.

PMID- 21171542
TI  - South Asian immigrant women's experiences of being respected within cancer
      treatment settings.
AB  - The purpose of this focused ethnographic inquiry was to examine South Asian
      immigrant women's experiences and perceptions of respect within health
      professional-client relationships in the context of a Canadian outpatient
      treatment clinic. Characteristics of respect described by 11 women interviewed
      were the meaning of respect, health professional's way of being, their way of
      attending to the person, and their way of talking. Language, cultural values and
      beliefs, along with underlying societal, individual and institutional factors
      that coexist with health professionals' ability to create respect were some of
      the dimensions that influenced how immigrant women experienced respect. Health
      professionals' capacity to acknowledge South Asian immigrant women as individuals
      helped to formulate/construct respect for their individual identities. The need
      to be respected for 'my social identity' as an immigrant woman with cancer was
      woven throughout women's stories, illustrated by their personal experiences and
      perspectives.

PMID- 21171543
TI  - Report from the Director-at-Large-- Education.

PMID- 21171544
TI  - Report from the Director-at-Large-- Professional Practice.

PMID- 21171545
TI  - Communities of practice: working in new ways to advance gynecologic oncology
      nursing.

PMID- 21171546
TI  - The semantics of secrecy: young children's classification of secret content.
AB  - The authors explored whether young children can distinguish potential secrets
      from nonsecrets by their content, as can older children, adolescents, and adults.
      Ninety children, 4, 5, and 6 years old, rated the secrecy of items from an adult
      validated list of personal information about an age- and gender-appropriate
      puppet. Two factors of the children's data corresponded to the adult categories
      of nonsecrets and secrets, and a third factor corresponded to surprises. All ages
      rated surprises as significantly more secret than nonsecret items; however, the
      surprise items contained linguistic cues to secrecy. A tendency to rate
      nonsecrets as secret decreased with age, but only the 6-year-olds rated secrets
      other than surprises as significantly more secret than nonsecrets. Thus, children
      acquire the implicit rules defining secret content from a somewhat later age than
      that reported for the cognitive or behavioral capacities for secrecy.

PMID- 21171547
TI  - Parental influences on memories of parents and friends.
AB  - The authors evaluated the role parent-child relationship quality has on two types
      of memories, those of parents and those of friends. Participants were 198 Italian
      university students who recalled memories during 4 separate timed memory-fluency
      tasks about their preschool, elementary school, middle school, high school and
      university years. Half were instructed to recall memories involving parents and
      the remainder memories involving friends. Moreover, parent-child relationships
      were assessed by the Network of Relationships Inventory (NRI; W. Furman & D.
      Buhrmester, 1985) and Adolescents' Report of Parental Monitoring (D. M. Capaldi &
      G. R. Patterson, 1989). Results showed that men with positive parent-son
      relationships had more memories of parents and more affectively positive memories
      of friends, supporting a consistency model positing similarity between parent
      child relationships and memories of friends. Women with positive parental
      relationship quality had more affectively positive memories of parents but for
      friends, positive relationship quality only predicted positive memories when
      young. At older ages, especially middle school-aged children, negative parent
      daughter relationships predicted more positive memories of friends, supporting a
      compensatory model. The gender of parent also mattered, with fathers having a
      more influential role on affect for memories of friends.

PMID- 21171548
TI  - Maternal socialization goals, parenting styles, and social-emotional adjustment
      among Chinese and European American young adults: testing a mediation model.
AB  - The authors compared the associations among perceived maternal socialization
      goals (self-development, filial piety, and collectivism), perceived maternal
      parenting styles (authoritative, authoritarian, and training), and the social
      emotional adjustment (self-esteem, academic self-efficacy, and depression)
      between Chinese and European American young adults. The mediation processes in
      which socialization goals relate to young adults' adjustment outcomes through
      parenting styles were examined. Results showed that European American
      participants perceived higher maternal self-development socialization goals,
      whereas Chinese participants perceived higher maternal collectivism socialization
      goals as well as more authoritarian parenting. Cross-cultural similarities were
      found in the associations between perceived maternal authoritative parenting and
      socioemotional adjustment (e.g., higher self-esteem and higher academic self
      efficacy) across the two cultural groups. However, perceived maternal
      authoritarian and training parenting styles were found only to be related to
      Chinese participants' adjustment (e.g., higher academic self-efficacy and lower
      depression). The mediation analyses showed that authoritative parenting
      significantly mediated the positive associations between the self-development and
      collectivism goal and socioemotional adjustment for both cultural groups.
      Additionally, training parenting significantly mediated the positive association
      between the filial piety goal and young adults' academic self-efficacy for the
      Chinese group only. Findings of this study highlight the importance of examining
      parental socialization goals in cross-cultural parenting research.

PMID- 21171549
TI  - Moral virtue and practical wisdom: theme comprehension in children, youth, and
      adults.
AB  - The authors tested 3 hypotheses about the relation of moral comprehension to
      prudential comprehension by contrasting comprehension of themes in moral stories
      with comprehension of themes in prudential stories among third-grade, fifth
      grade, and college students (n = 168) in Study 1, and among college students,
      young and middle-aged adults, and older adults (n = 96) in Study 2. In both
      studies, all groups were statistically significantly better at moral theme
      comprehension than prudential theme comprehension, suggesting that moral
      comprehension may develop prior to prudential comprehension. In Study 2, all
      groups performed equally on moral theme generation whereas both adult groups were
      significantly better than college students on prudential theme generation.
      Overall, the findings of these studies provide modest evidence that moral and
      prudential comprehension each develop separately, and that the latter may develop
      more slowly.

PMID- 21171551
TI  - Nursing M & M conference: help in healing from a serious event.

PMID- 21171550
TI  - That's a boy's toy: gender-typed knowledge in toddlers as a function of mother's
      marital status.
AB  - A child who is highly gender schematic readily uses gender when processing new
      information. In the current study, we examined whether and how family structure
      predicts a child's level of gender-typed knowledge (as assessed by a gender
      stereotype sorting task) once the category of gender is in place (as assessed by
      a gender-labeling task). It was predicted that children from more "traditional"
      family structures (married mothers) would have more gender-typed knowledge
      compared to children from less traditional families (unmarried mothers).
      Moreover, we explored if this relationship would be related to, at least in part,
      the greater frequency of androgynous behaviors (i.e., both masculine and feminine
      household activities) an unmarried mother performs. Twenty-eight children (age 2
      to 3) were tested at local childcare centers. The mother of each child reported
      her marital status as well as how often she engaged in stereotypically masculine
      and feminine behaviors. As expected, mothers' marital status was associated with
      children's level of gender-typed knowledge, such that children with unmarried
      mothers had less gender-typed knowledge, in part due to the unmarried mother's
      greater frequency of androgynous behaviors. Implications for children's
      acquisition of gender-related stereotypes and the possible benefit of having
      mothers model both masculine and feminine behaviors are discussed.

PMID- 21171552
TI  - Initiative: greater role for nursing.

PMID- 21171553
TI  - Help in evaluating bone allografts.

PMID- 21171554
TI  - Bone allografts: options for healing.

PMID- 21171555
TI  - Making good choices of DBM products.

PMID- 21171556
TI  - Business manager salaries top $78,000.

PMID- 21171557
TI  - The price is right for cost awareness.

PMID- 21171558
TI  - Onboarding: laying the foundation.

PMID- 21171559
TI  - Predicting frailty risk in older patients.

PMID- 21171560
TI  - Steps to preventing DVT for outpatients.

PMID- 21171561
TI  - Analytical solution for the modeling of the natural time-dependent reduction of
      waterborne viruses injected into fractured aquifers.
AB  - We propose an analytical solution in order to explain the processes that
      determine the fate and behavior of the viruses during transport in a fractured
      aquifer at Salento (Italy). The calculations yield the efficiency of filtration
      in fractures at a site near Nardo (Southern Italy) in reducing the numbers of
      enteric viruses (i.e., Enteroviruses and Norovirus) in secondary municipal
      effluents that have been injected in the aquifer over the period 2006-2007. The
      model predicted, by a theoretical expression, the time-dependent rate of virus
      reduction, which was in good agreement with field data. The analytical solution
      yields the achievable "Log reduction credits" for virus reduction in wells
      located at the setback distances that are usually adopted in local drinking water
      regulations. The resulting new analytical formula for the time-dependent
      reduction of viruses during subsurface transport can easily be applied in health
      risk-based models used to forecast the spread of waterborne diseases and provides
      appropriate criteria (i.e., distances) needed to meet standards for the quality
      of drinking water derived from undisinfected groundwater.

PMID- 21171562
TI  - Pollutant concentrations within households in Lao PDR and association with
      housing characteristics and occupants' activities.
AB  - The paper presents the results of a study conducted to investigate indoor air
      quality within residential dwellings in Lao PDR. Results from PM(10), CO, and
      NO(2) measurements inside 167 dwellings in Lao PDR over a five month period
      (December 2005-April 2006) are discussed as a function of household
      characteristics and occupant activities. Extremely high PM(10) and NO(2)
      concentrations (12 h mean PM(10) concentrations 1275 +/- 98 MUg m(-3) and 1183 +/
      99 MUg m(-3) in Vientiane and Bolikhamxay provinces, respectively; 12 h mean
      NO(2) concentrations 1210 +/- 94 MUg m(-3) and 561 +/- 45 MUg m(-3) in Vientiane
      and Bolikhamxay, respectively) were measured within the dwellings. Correlations,
      ANOVA analysis (univariate and multivariate), and linear regression results
      suggest a substantial contribution from cooking and smoking. The PM(10)
      concentrations were significantly higher in houses without a chimney compared to
      houses in which cooking occurred on a stove with a chimney. However, no
      significant differences in pollutant concentrations were observed as a function
      of cooking location. Furthermore, PM(10) and NO(2) concentrations were higher in
      houses in which smoking occurred, suggestive of a relationship between increased
      indoor concentrations and smoking (0.05 < p < 0.10). Resuspension of dust from
      soil floors was another significant source of PM(10) inside the house (634 MUg m(
      3), p < 0.05).

PMID- 21171563
TI  - Environmental responsiveness of polygalacturonic acid-based multilayers to
      variation of pH.
AB  - The effect of pH on the stability of layer-by-layer deposited polygalacturonic
      acid (PGalA)-based multilayer films prepared with the polycations poly-L-lysine,
      chitosan, and lysozyme is studied. The response was characterized using a quartz
      crystal microbalance, dual polarization interferometry, and Fourier transform
      infrared spectroscopy which probe multilayer thickness, density, polymer mass
      (composition and speciation), and hydration. All multilayers showed irreversible
      changes in response to pH change becoming thinner due to the partial disassembly.
      Preferential loss of the polycation (50-80% w/w) and relative small losses of
      PGaLA (10-35% w/w) occurred. The charge density on the polycation has a strong
      influence on the response to the acid cycle. Most of the disassembly takes place
      at the pH lower that pK(a) of PGaLA, indicating that this factor was crucial in
      determining the stability of the films. The pH challenge also revealed a
      polycation-dependent shift to acid pH in the PGaLA pK(a).

PMID- 21171564
TI  - Depletion force between anisometric colloidal particles.
AB  - A simple mathematical model for the depletion force between two arbitrarily
      shaped large convex colloidal particles immersed in a suspension of small
      spherical particles is proposed. Using differential geometry, the interaction
      potential is expressed in terms of the mean and Gaussian curvature of the
      particle surfaces. The accuracy of theoretical results is tested by Monte Carlo
      simulations for parallel and nonparallel circular cylinders. The agreement
      between theoretical results and simulated data is very good if the density of the
      depletion agent is not too high.

PMID- 21171565
TI  - Salt induced irreversible protein adsorption with extremely high loadings on
      electrospun nanofibers.
AB  - LiCl is a kosmotrope that generally promotes protein salvation in aqueous
      solutions. Herein we report that LiCl embedded in electrospun polymeric
      nanofibers interestingly induced an abnormal protein adsorption and substantially
      augmented the adsorption capacity of the fibers. As a result, equilibrium protein
      loadings reached over 64% (w/w) of the dry mass of fibers, 9-fold higher than
      that observed in the absence of the salt. The adsorption appeared to be
      irreversible such that little protein loss was observed even after washing the
      fibers vigorously with fresh buffer solutions. We further examined the
      application of such intensified protein adsorption for enzyme immobilization.
      Proteins including bovine serum albumin (BSA) and protamine were first adsorbed,
      followed by covalent attachment of an outer layer of an enzyme, alpha
      chymotrypsin. Such a multilayer-structured nanofibrous enzyme exhibited extremely
      high stability with no obvious activity loss even after being incubated for 8
      months at 4  degrees C in aqueous buffer solution. The LiCl induced irreversible
      protein adsorption, which has been largely ignored in previous studies with
      electrospun materials, rendering an interesting scenario of interfacial protein
      material interactions. It also reveals a new mechanism in controlling and
      fabricating molecular interactions at interfaces for development of a broad range
      of biomaterials.

PMID- 21171566
TI  - Controlling the neuronal differentiation of stem cells by the intracellular
      delivery of retinoic acid-loaded nanoparticles.
AB  - The manipulation of endogenous stem cell populations from the subventricular zone
      (SVZ), a neurogenic niche, creates an opportunity to induce neurogenesis and
      influence brain regenerative capacities in the adult brain. Herein, we
      demonstrate the ability of polyelectrolyte nanoparticles to induce neurogenesis
      exclusively after being internalized by SVZ stem cells. The nanoparticles are not
      cytotoxic for concentrations equal or below 10 MUg/mL. The internalization
      process is rapid, and nanoparticles escape endosomal fate in a few hours.
      Retinoic acid-loaded nanoparticles increase the number of neuronal nuclear
      protein (NeuN)-positive neurons and functional neurons responding to
      depolarization with KCl and expressing NMDA receptor subunit type 1 (NR1). These
      nanoparticles offer an opportunity for in vivo delivery of proneurogenic factors
      and neurodegenerative disease treatment.

PMID- 21171568
TI  - Thermal dynamics of graphene edges investigated by polarized Raman spectroscopy.
AB  - In this report, we present Raman spectroscopy investigation of the thermal
      stability and dynamics of graphene edges. It is found that graphene edges (both
      armchair and zigzag) are not stable and undergo modifications even at temperature
      as low as 200  degrees C. On the basis of polarized Raman results, we provide
      possible structural models on how graphene edges change during annealing. The
      zigzag edges rearrange and form armchair segments that are +/-30 degrees 
      relative to the edge direction, while armchair edges are dominated by armchair
      segments even at annealing temperature as high as 500  degrees C. The
      modifications of edge structures by thermal annealing (zigzag segments rearrange
      in form of armchair segments) provide a flexible way to control the electronic
      properties of graphene and graphene nanostructures.

PMID- 21171567
TI  - Noninvasive photoacoustic and fluorescence sentinel lymph node identification
      using dye-loaded perfluorocarbon nanoparticles.
AB  - The contrast mechanisms used for photoacoustic tomography (PAT) and fluorescence
      imaging differ in subtle, but significant, ways. The design of contrast agents
      for each or both modalities requires an understanding of the spectral
      characteristics as well as intra- and intermolecular interactions that occur
      during formulation. We found that fluorescence quenching that occurs in the
      formulation of near-infrared (NIR) fluorescent dyes in nanoparticles results in
      enhanced contrast for PAT. The ability of the new PAT method to utilize strongly
      absorbing chromophores for signal generation allowed us to convert a highly
      fluorescent dye into an exceptionally high PA contrast material. Spectroscopic
      characterization of the developed NIR dye-loaded perfluorocarbon-based
      nanoparticles for combined fluorescence and PA imaging revealed distinct dye
      dependent photophysical behavior. We demonstrate that the enhanced contrast
      allows detection of regional lymph nodes of rats in vivo with time-domain optical
      and photoacoustic imaging methods. The results further show that the use of
      fluorescence lifetime imaging, which is less dependent on fluorescence intensity,
      provides a strategic approach to bridge the disparate contrast reporting
      mechanisms of fluorescence and PA imaging methods.

PMID- 21171570
TI  - Self-consistent-field and hybrid particle-field theory simulation of confined
      copolymer and nanoparticle mixtures.
AB  - In this paper, we used combined self-consistent-field and hybrid particle-field
      theory to explore the self-assembly behavior of diblock copolymer-nanoparticle
      mixtures confined between two concentric circular walls. The simulation reveals
      that the structural frustration, the loss of conformational entropy of the
      copolymer, and the radii of the two concentric circles have great influence on
      the morphologies of the system. We also discuss the underlying mechanism of
      controlling the self-assembly of such a system in terms of enthalpic interaction
      between particles and copolymers, steric repulsive interactions between
      particles, and the conformational entropy of copolymers, and a representative
      phase diagram in terms of block ratio and the particle volume fraction is
      constructed. This study suggests a route to help experimentalists better create
      high-performance nanodevices.

PMID- 21171571
TI  - Schizanthines N, O, and P, tropane alkaloids from the aerial parts of Schizanthus
      tricolor.
AB  - Three tropane alkaloids, named schizanthines N, O, and P (1-3), have been
      isolated from the crude alkaloid extract of the endemic Chilean plant Schizanthus
      tricolor. On the basis of extensive NMR studies and MS fragmentation analysis,
      their structures were determined to be 3alpha-(E)-4-hydroxysenecioyloxy-6beta
      angeloyloxytropane (1), 3alpha-(E)-4-hydroxysenecioyloxy-6beta
      senecioyloxytropane (2), and 3alpha-mesaconyloxy-6beta-senecioyloxytropane (3).
      Compounds 1 and 2 are the first isomeric alkaloids in the tropane series
      possessing a hydroxysenecioyl substituent as an esterifying moiety.

PMID- 21171572
TI  - Photosynthetic oxygen evolution in mesoporous silica material: adsorption of
      photosystem II reaction center complex into 23 nm nanopores in SBA.
AB  - An oxygen-evolving photosynthetic reaction center complex (PSII) was adsorbed
      into nanopores in SBA, a mesoporous silica compound. We purified the dimer of
      PSII complex from a thermophilic cyanobacterium, Thermosynechococcus vulcanus,
      which grows optimally at 57  degrees C. The thermally stable PSII dimeric complex
      has a diameter of 20 nm and a molecular mass of 756 kDa and binds more than 60
      chlorophylls. The SBA particles, with average internal pore diameters of 15 nm
      (SBA(15)) and 23 nm (SBA(23)), adsorbed 4.7 and 15 mg of PSII/g SBA,
      respectively. Measurement with a confocal laser-scanning microscope indicated the
      adsorption of PSII to the surface and the inner space of the SBA(23) particles,
      indicating the adsorption of PSII into the 23 nm silica nanopores. PSII did not
      bind to the inner pores of SBA(15). PSII bound to SBA(23) showed the high and
      stable activity of a photosynthetic oxygen-evolving reaction, indicating the
      light-driven electron transport from water to the quinone molecules added in the
      outer medium. The PSII-SBA conjugate can be a new material for photosensors and
      artificial photosynthetic systems.

PMID- 21171573
TI  - Does the TauD enzyme always hydroxylate alkanes, while an analogous synthetic non
      heme reagent always desaturates them?
AB  - This theoretical work addresses the mechanistic switch between hydroxylase
      (alcohol formation) and desaturase (olefin formation) activities during alkane
      oxidation by two non-heme high-valent oxoiron reagents, the enzyme taurine:alpha
      ketoglutarase dioxygenase (TauD) and the synthetic shape-selective catalyst
      (TpOBzFe), toward cyclohexadiene, cyclohexane, cyclopentane, and ethane. As we
      show, the desaturase/hydroxylase steps obey unique orbital selection rules, and
      the mechanistic switch is determined by intrinsic reactivity factors that depend
      on the ligand-sphere flexibility of the oxoiron species, the substrate, and the
      spin states of the reaction pathways. Testable predictions are outlined.

PMID- 21171574
TI  - Photoinduced rearrangements of 3,3'-bis(arylbenzofurans).
AB  - Complex tetracyclic ring systems were assembled by a photoinduced rearrangement
      of 3,3'-bis(arylbenzofurans). Irradiation of 1 under N(2) atmosphere yielded the
      benzonaphthofurans 2 in 75-90% yield. When the reaction was conducted under an
      O(2) atmosphere in the presence of tetracyanoethylene (TCNE) a different reaction
      pathway was observed leading to the isolation of 3 as the major product. Also,
      the photochemical properties of these novel structures were investigated.

PMID- 21171575
TI  - Ab initio insights on the shapes of platinum nanocatalysts.
AB  - Catalytic, chemical, optical, and electronic properties of nanocrystals are
      strongly influenced by their faceting. A variational approach based on quantum
      mechanical energies is introduced to evaluate stable and metastable shapes of Pt
      nanocrystals. The method leads to a nanoscale equation of state, which is solved
      self-consistently. It is found that the surface energy dependence on the lattice
      parameter is the key factor controlling the equilibrium stability of the crystal
      shapes. The variational approach, capable of predicting the changes in the
      hierarchy of crystals' shapes with respect to size, explains experimental results
      and establishes a new direction to search for better catalysts.

PMID- 21171576
TI  - Magnetic response of single-walled carbon nanotubes induced by an external
      magnetic field.
AB  - Using first-principles density functional calculations, magnetically induced
      currents are obtained for zigzag single-walled carbon nanotubes. Clear
      differences and trends in current flow are observed between the different
      nanotube families. In particular, for a magnetic field applied along the tube
      axis, the current response of the lambda = 0 infinite nanotubes is paramagnetic,
      whereas for lambda = 1 and 2 nanotubes, the response is diamagnetic. The results
      are used to predict and interpret the significant changes in NMR properties for
      small molecules encapsulated inside a tube.

PMID- 21171577
TI  - Copper-catalyzed conjugate additions of alkylboranes to imidazolyl alpha,beta
      unsaturated ketones: formal reductive conjugate addition of terminal alkenes.
AB  - Conjugate addition of alkylboron compounds (alkyl-9-BBN) to imidazol-2-yl
      alpha,beta-unsaturated ketones proceeded in the presence of a catalytic amount
      (10 mol %) of CuCl, 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes), and
      t-BuOK. The alkylboranes are available through alkene hydroboration, and thus the
      overall process represents a reductive conjugate addition of alkenes to enone
      derivatives. A variety of functional groups are tolerated in both the alkenes and
      the alpha,beta-unsaturated ketones. The 2-acylimidazole moiety can easily be
      converted into the corresponding carboxylic acid, ester, and amide derivatives.

PMID- 21171579
TI  - Stabilization of magnetic iron oxide nanoparticles in biological media by fetal
      bovine serum (FBS).
AB  - A facile method of stabilizing magnetic iron oxide nanoparticles (MNPs) in
      biological media (RPMI-1640) via surface modification with fetal bovine serum
      (FBS) is presented herein. Dynamic light scattering (DLS) shows that the size of
      the MNP aggregates can be maintained at 190 +/- 2 nm for up to 16 h in an RPMI
      1640 culture medium containing >=4 vol % FBS. Under transmission electron
      microscopy (TEM), a layer of protein coating is observed to cover the MNP surface
      following treatment with FBS. The adsorption of proteins is further confirmed by
      X-ray photoelectron spectroscopy (XPS). Gel electrophoresis and LC-MS/MS studies
      reveal that complement factor H, antithrombin, complement factor I, alpha-1
      antiproteinase, and apolipoprotein E are the proteins most strongly attached to
      the surface of an MNP. These surface-adsorbed proteins serve as a linker that
      aids the adsorption of other serum proteins, such as albumin, which otherwise
      adsorb poorly onto MNPs. The size stability of FBS-treated MNPs in biological
      media is attributed to the secondary adsorbed proteins, and the size stability in
      biological media can be maintained only when both the surface-adsorbed proteins
      and the secondary adsorbed proteins are present on the particle's surface.

PMID- 21171580
TI  - Study of superhydrophobic electrospun nanocomposite fibers for energy systems.
AB  - Polystyrene (PS) and polyvinyl chloride (PVC) fibers incorporated into TiO(2)
      nanoparticles and graphene nanoflakes were fabricated by an electrospinning
      technique, and then the surface morphology and superhydrophobicity of these
      electrospun nanocomposite fibers were investigated. Results indicated that the
      water contact angle of the nanocomposite fiber surfaces increases to 178 degrees 
      on the basis of the fiber diameter, material type, nanoscale inclusion, heat
      treatment, and surface porosity/roughness. This is a result of the formation of
      the Cassie-Baxter state in the fibers via the nanoparticle decoration, bead
      formation, and surface energy of the nanofiber surface. Consequently, these
      superhydrophobic nanocomposite fibers can be utilized in designing
      photoelectrodes of dye-sensitized solar cells (DSSCs) as self-cleaning and anti
      icing materials for the long-term efficiency of the cells.

PMID- 21171582
TI  - Pair distribution function analysis and solid state NMR studies of silicon
      electrodes for lithium ion batteries: understanding the (de)lithiation
      mechanisms.
AB  - Lithium ion batteries (LIBs) containing silicon negative electrodes have been the
      subject of much recent investigation, because of the extremely large gravimetric
      and volumetric capacities of silicon. The crystalline-to-amorphous phase
      transition that occurs on electrochemical Li insertion into crystalline Si,
      during the first discharge, hinders attempts to link the structure in these
      systems with electrochemical performance. We apply a combination of local
      structure probes, ex situ (7)Li nuclear magnetic resonance (NMR) studies, and
      pair distribution function (PDF) analysis of X-ray data to investigate the
      changes in short-range order that occur during the initial charge and discharge
      cycles. The distinct electrochemical profiles observed subsequent to the first
      discharge have been shown to be associated with the formation of distinct
      amorphous lithiated silicide structures. For example, the first process seen on
      the second discharge is associated with the lithiation of the amorphous Si,
      forming small clusters. These clusters are broken in the second process to form
      isolated silicon anions. The (de)lithiation model helps explain the hysteresis
      and the steps in the electrochemical profile observed during the lithiation and
      delithiation of silicon.

PMID- 21171581
TI  - Three clusters of conformational states in p450cam reveal a multistep pathway for
      closing of the substrate access channel.
AB  - Conformational changes in the substrate access channel have been observed for
      several forms of cytochrome P450, but the extent of conformational plasticity
      exhibited by a given isozyme has not been completely characterized. Here we
      present crystal structures of P450cam bound to a library of 12 active site probes
      containing a substrate analogue tethered to a variable linker. The structures
      provide a unique view of the range of protein conformations accessible during
      substrate binding. Principal component analysis of a total of 30 structures
      reveals three discrete clusters of conformations: closed (P450cam-C),
      intermediate (P450cam-I), and fully open (P450cam-O). Relative to P450cam-C, the
      P450cam-I state results predominantly from a retraction of helix F, while both
      helices F and G move in concert to reach the fully open P450cam-O state. Both
      P450cam-C and P450cam-I are well-defined states, while P450cam-O shows evidence
      of a somewhat broader distribution of conformations and includes the open form
      recently seen in the absence of substrate. The observed clustering of protein
      conformations over a wide range of ligand variants suggests a multistep closure
      of the enzyme around the substrate that begins by conformational selection from
      an ensemble of open conformations and proceeds through a well-defined
      intermediate, P450cam-I, before full closure to the P450cam-C state in the
      presence of small substrates. This multistep pathway may have significant
      implications for a full understanding of substrate specificity, kinetics, and
      coupling of substrate binding to P450 function.

PMID- 21171583
TI  - Occurrence of fumonisins B(2) and B(4) in retail raisins.
AB  - Concerns that raisins may be contaminated by fumonisins stem from the persistent
      occurrence of Aspergillus niger spores on raisins and the recent discovery of
      fumonisin production by A. niger on grapes, which leads to the widespread
      occurrence of fumonisin B(2) in wine. This study presents an LC-MS/MS survey of
      fumonisins in retail raisins. In 10 of 21 brands collected in Denmark, Germany,
      and The Netherlands, fumonisins B(2) and B(4) were detected at levels up to 13
      and 1.3 MUg/kg, respectively. Only fumonisin B(2) has been detected in wine, so
      the presence of fumonisin B(4) in raisins suggests that the fumonisins are
      produced mainly during the drying process concomitant with the decreasing water
      activity. Analysis of multiple packages from one manufacturer showed a 3-fold
      package-to-package variation, suggesting that a few raisins per package are
      contaminated.

PMID- 21171584
TI  - Snake venomics of African spitting cobras: toxin composition and assessment of
      congeneric cross-reactivity of the pan-African EchiTAb-Plus-ICP antivenom by
      antivenomics and neutralization approaches.
AB  - Venomic analysis of the venoms of Naja nigricollis, N. katiensis, N. nubiae, N.
      mossambica, and N. pallida revealed similar compositional trends. The high
      content of cytotoxins and PLA(2)s may account for the extensive tissue necrosis
      characteristic of the envenomings by these species. The high abundance of a type
      I alpha-neurotoxin in N. nubiae may be responsible for the high lethal toxicity
      of this venom (in rodents). The ability of EchiTAb-Plus-ICP antivenom to
      immunodeplete and neutralize the venoms of African spitting cobras was assessed
      by antivenomics and neutralization tests. It partially immunodepleted 3FTx and
      PLA(2)s and completely immunodepleted SVMPs and CRISPs in all venoms. The
      antivenom neutralized the dermonecrotic and PLA(2) activities of all African Naja
      venoms, whereas lethality was eliminated in the venoms of N. nigricollis, N.
      mossambica, and N. pallida but not in those of N. nubiae and N. katiensis. The
      lack of neutralization of lethality of N. nubiae venom may be of medical
      relevance only in relatively populous areas of the Saharan region. The impaired
      activity of EchiTAb-Plus-ICP against N. katiensis may not represent a major
      concern. This species is sympatric with N. nigricollis in many regions of Africa,
      although very few bites have been attributed to it.

PMID- 21171585
TI  - Capping methotrexate alpha-carboxyl groups enhances systemic exposure and retains
      the cytotoxicity of drug conjugated PEGylated polylysine dendrimers.
AB  - A generation 5 PEGylated (PEG 1100) polylysine dendrimer, conjugated via a stable
      amide linker to OtBu protected methotrexate (MTX), was previously shown to have a
      circulatory half-life of 2 days and to target solid tumors in both rats and mice.
      Here, we show that deprotection of MTX and substitution of the stable linker with
      a matrix metalloproteinase (MMP) 2 and 9 cleavable linker (PVGLIG) dramatically
      increased plasma clearance and promoted deposition in the liver and spleen (50
      80% of the dose recovered in the liver 3 days post dose). Similar rapid clearance
      was also seen using a scrambled peptide suggesting that clearance was not
      dependent on the cleavable nature of the linker. Surprisingly, dendrimers where
      OtBu capped MTX was linked to the dendrimer surface via the hexapeptide linker
      showed equivalent in vitro cytotoxicity against HT1080 cells when compared to the
      uncapped dendrimer and also retained the long circulating characteristics of the
      stable constructs. The OtBu capped MTX conjugated dendrimer was subsequently
      shown to significantly reduce tumor growth in HT1080 tumor bearing mice compared
      to control. In contrast the equivalent dendrimer comprising uncapped MTX
      conjugated to the dendrimer via the same hexapeptide linker did not reduce tumor
      growth, presumably reflecting very rapid clearance of the construct. The results
      are consistent with the suggestion that protection of the alpha-carboxyl group of
      methotrexate may be used to improve the circulatory half-life and reduce the
      liver accumulation of similar MTX-conjugated dendrimers, while still retaining
      antitumor activity in vivo.

PMID- 21171587
TI  - Predicting the binding mode of known NCp7 inhibitors to facilitate the design of
      novel modulators.
AB  - The HIV-1 nucleocapsid protein (NCp7) is an emerging target for antiretroviral
      therapy. Five hits have been reported to inhibit the NCp7-viral nucleic acids
      interaction at micromolar concentrations. We used two computationally refined
      structures of NCp7 as receptors to propose a reliable binding pose for these
      compounds, by means of computational methods. Theoretical binding modes are in
      agreement with available experimental data. Results lay the foundations for a
      rationale development of more effective NCp7 inhibitors.

PMID- 21171586
TI  - Atomistic simulation and measurement of pH dependent cancer therapeutic
      interactions with nanodiamond carrier.
AB  - In this work, we have combined constant-pH molecular dynamics simulations and
      experiments to provide a quantitative analysis of pH dependent interactions
      between doxorubicin hydrochloride (DOX) cancer therapeutic and faceted
      nanodiamond (ND) nanoparticle carriers. Our study suggests that when a mixture of
      faceted ND and DOX is dissolved in a solvent, the pH of this solvent plays a
      controlling role in the adsorption of DOX molecules on the ND. We find that the
      binding of DOX molecules on ND occurs only at high pH and requires at least ~10%
      of ND surface area to be fully titrated for binding to occur. As such, this study
      reveals important mechanistic insight underlying an ND-based pH-controlled
      therapeutic platform.

PMID- 21171588
TI  - Two-dimensional terahertz correlation spectra of electronic excitations in
      semiconductor quantum wells.
AB  - We discuss a novel approach for nonlinear two-dimensional (2D) spectroscopy in
      the terahertz (THz) frequency range which is based on a collinear interaction
      geometry of a sequence of THz pulses with the sample. The nonlinear polarization
      is determined by a phase-resolved measurement of the electric field transmitted
      through the sample as a function of the delay tau between two phase-locked pulses
      and the "real" time t. The information provided by a single 2D scan along the tau
      and t axes is equivalent to that from a noncollinear photon-echo setup equipped
      with four local oscillators, each interacting with a different diffracted order.
      We address basic concepts of collinear 2D THz spectroscopy, in particular data
      analysis and phasing issues. Different rephasing and nonrephasing contributions
      to the third-order response are separated and 2D correlation spectra derived. As
      a prototype application, 2D correlation spectra of intersubband excitations of
      electrons in semiconductor quantum wells are presented.

PMID- 21171590
TI  - Intrinsic Z-DNA is stabilized by the conformational selection mechanism of Z-DNA
      binding proteins.
AB  - Z-DNA, a left-handed isoform of Watson and Crick's B-DNA, is rarely formed
      without the help of high salt concentrations or negative supercoiling. However, Z
      DNA-binding proteins can efficiently convert specific sequences of the B
      conformation into the Z conformation in relaxed DNA under physiological salt
      conditions. As in the case of many other specific interactions coupled with
      structural rearrangements in biology, it has been an intriguing question whether
      the proteins actively induce Z-DNAs or passively trap transiently preformed Z
      DNAs. In this study, we used single-molecule fluorescence assays to observe
      intrinsic B-to-Z transitions, protein association/dissociation events, and
      accompanying B-to-Z transitions. The results reveal that intrinsic Z-DNAs are
      dynamically formed and effectively stabilized by Z-DNA-binding proteins through
      efficient trapping of the Z conformation rather than being actively induced by
      them. Our study provides, for the first time, detailed pictures of the intrinsic
      B-to-Z transition dynamics and protein-induced B-to-Z conversion mechanism at the
      single-molecule level.

PMID- 21171591
TI  - Conjugated zwitterionic polyelectrolyte as the charge injection layer for high
      performance polymer light-emitting diodes.
AB  - A new zwitterionic conjugated polyelectrolyte without free counterions has been
      used as an electron injection material in polymer light-emitting diodes. Both the
      efficiency and maximum brightness were considerably improved in comparison with
      standard Ca cathode devices. The devices showed very fast response times,
      indicating that the improved performance is, in addition to hole blocking, due to
      dipoles at the cathode interface, which facilitate electron injection.

PMID- 21171593
TI  - Specific detection of D-glucose by a tetraphenylethene-based fluorescent sensor.
AB  - A conceptually new "light-up" biosensor with a high specificity for d-glucose
      (Glu) in aqueous media has been developed. The emission from a tetraphenylethene
      (TPE)-cored diboronic acid (1) was greatly boosted when the fluorogen was
      oligomerized with Glu because of restriction of the intramolecular rotations of
      the aryl rotors of TPE by formation of the oligomer. Little change in the light
      emission was observed when 1 was mixed with D-fructose, D-galactose, or D
      mannose, as these saccharides are unable to oligomerize with the fluorogen.

PMID- 21171592
TI  - Novel pyrrolopyrimidine-based alpha-helix mimetics: cell-permeable inhibitors of
      protein-protein interactions.
AB  - There is considerable interest in developing non-peptidic, small-molecule alpha
      helix mimetics to disrupt alpha-helix-mediated protein-protein interactions.
      Herein, we report the design of a novel pyrrolopyrimidine-based scaffold for such
      alpha-helix mimetics with increased conformational rigidity. We also developed a
      facile solid-phase synthetic route that is amenable to divergent synthesis of a
      large library. Using a fluorescence polarization-based assay, we identified cell
      permeable, dual MDMX/MDM2 inhibitors, demonstrating that the designed molecules
      can act as alpha-helix mimetics.

PMID- 21171594
TI  - A biocompatible oxidation-triggered carrier polymer with potential in
      therapeutics.
AB  - Dextran, a water-soluble, biocompatible polymer of glucose, was modified at its
      hydroxyls with arylboronic esters to make it soluble in common organic solvents,
      allowing for the facile preparation of oxidation-sensitive dextran (Oxi-DEX)
      carrier microparticles. These particles were found to release their payload with
      a half-life of 36 min at 1 mM H2O2, which can be compared with a half-life of
      greater than 1 week in the absence of H2O2. When used in a model vaccine
      application, Oxi-DEX particles loaded with ovalbumin (OVA) increased the
      presentation to CD8+ T-cells 27-fold relative to OVA encapsulated in a classical
      vehicle not sensitive to oxidation. No presentation was observed from cells
      incubated with unencapsulated OVA. Additionally, Oxi-DEX was found to be nontoxic
      in preliminary in vitro cytotoxicity assays. Because it is easy to prepare,
      sensitive to biological oxidation, and biocompatible, this material may represent
      an attractive new platform for selective delivery applications.

PMID- 21171595
TI  - Highly selective oligosaccharide sensing by a Curdlan-polythiophene hybrid.
AB  - An in situ hybrid complex of Curdlan with water-soluble polythiophene functioned
      as a highly sensitive and selective saccharide chemosensor in aqueous media,
      enabling us to discriminate tetrasaccharide acarbose at 1 MUM from 24 mono-, di-,
      tri-, tetra-, and pentasaccharides.

PMID- 21171596
TI  - Novel dose metric for apparent cytotoxicity effects generated by in vitro cell
      exposure to silica nanoparticles.
AB  - This study aimed at identifying the dose metric applicable to studies on the
      viability of cells exposed to nanoparticles (NPs) in vitro. A previously reported
      set of data was evaluated very carefully. The extent of cell death after 24-h
      exposure of three cell lines to suspended silica NPs (<30 nm) was quantified
      using four different viability/cytotoxicity assays. Data on NP uptake in cells
      after 6-h exposure were also reported. Evidence is provided that, in spite of the
      small size of the NPs, mass transport to the cells cannot be explained solely by
      diffusion. Gravitational settling must have contributed significantly, presumably
      as the result of the formation of large agglomerates. Appropriately adjusted
      response data, with typically 22 combinations of mass concentration and height of
      the medium for each cell line, could be integrated in universal diagrams,
      provided the dose was quoted in terms of the areal density of NP mass delivered
      to the cells. Loss of viability became observable only if cells were exposed to
      the equivalent of 1 to 5 closely packed layers of NPs; the dose required for
      complete cell death ranged between 4 and about 20 layers of NPs. The results
      suggest that the cell-death phenomena observed in the evaluated work and in many
      similar studies reported in the literature constitute a matter of cell overload
      with nanostructured matter. This finding also implies that the toxic potential of
      individual silicate NPs is very low. Strategies for the design of advanced future
      work are outlined.

PMID- 21171597
TI  - Energetically important C-H...F-C pseudohydrogen bonding in water: evidence and
      application to rational design of oligonucleotides with high binding affinity.
AB  - It is controversial whether organic fluorine can form energetically important
      hydrogen bonds in aqueous environments. We previously showed by NMR and molecular
      modeling that the unexpectedly high binding affinity of 2'F-ANA is largely due to
      a C-H...F-C pseudohydrogen bond at pyrimidine-purine steps. Comparisons of the
      melting of duplexes with identical sequence composition but a rearranged sequence
      confirm that energetically important fluorine-mediated pseudohydrogen bonding is
      in operation in these sequences. The effect is of particular importance when the
      H-bond donor (purine H8) is activated by the presence of fluorine at its own 2'
      position. These results provide a rational method to increase the binding
      affinity of antisense oligonucleotides by placement of 2'F-ANA modifications at
      pyrimidine-purine steps.

PMID- 21171598
TI  - Oxidative kinetic self-sorting of a dynamic imine library.
AB  - Dynamic libraries of [n * n] imine components spontaneously simplify during a
      slow oxidation reaction to produce only n discrete products. The selectivity of
      this self-sorting process is a consequence of different oxidation rates for
      various imines, while the dynamic nature of the library enables self-sorting to
      proceed with high efficiency.

PMID- 21171599
TI  - Formation of vinyl-, vinylhalide- or acyl-substituted quaternary carbon
      stereogenic centers through NHC-Cu-catalyzed enantioselective conjugate additions
      of Si-containing vinylaluminums to beta-substituted cyclic enones.
AB  - A catalytic method for enantioselective conjugate addition (ECA) of Si-containing
      vinylaluminum reagents to beta-substituted cyclopentenones and cyclohexenones is
      described. Reactions are promoted by 1.0-5.0 mol % of a bidentate NHC-Cu complex,
      which is prepared from air-stable CuCl(2)*2H(2)O and used in situ, and typically
      proceed to completion within 15-20 min. The requisite vinylmetals are generated
      efficiently by a site-selective hydroalumination of an alkyne with dibal-H. The
      desired products, containing a quaternary carbon stereogenic center, are obtained
      in 48-95% yield after purification and in 89:11 to >98:2 enantiomer ratio (er).
      The vinylsilane moiety within the products can be functionalized to afford acyl,
      vinyliodide, or desilylated alkenes in 67% to >98% yield and with >90% retention
      of the alkene's stereochemical identity. The utility of the catalytic process is
      illustrated in the context of a concise enantioselective synthesis of
      riccardiphenol B.

PMID- 21171600
TI  - Geometrical separation method for lipoproteins using bioformulated-fiber matrix
      electrophoresis: size of high-density lipoprotein does not reflect its density.
AB  - The increasing number of patients with metabolic syndrome is a critical global
      problem. In this study, we describe a novel geometrical electrophoretic
      separation method using a bioformulated-fiber matrix to analyze high-density
      lipoprotein (HDL) particles. HDL particles are generally considered to be a
      beneficial component of the cholesterol fraction. Conventional electrophoresis is
      widely used but is not necessarily suitable for analyzing HDL particles.
      Furthermore, a higher HDL density is generally believed to correlate with a
      smaller particle size. Here, we use a novel geometrical separation technique
      incorporating recently developed nanotechnology (Nata de Coco) to contradict this
      belief. A dyslipidemia patient given a 1-month treatment of fenofibrate showed an
      inverse relationship between HDL density and size. Direct microscopic observation
      and morphological observation of fractionated HDL particles confirmed a lack of
      relationship between particle density and size. This new technique may improve
      diagnostic accuracy and medical treatment for lipid related diseases.

PMID- 21171601
TI  - Switching the conductance of Dy nanocontacts by magnetostriction.
AB  - The electrical conductance G of mechanical break-junctions fabricated from the
      rare-earth metal dysprosium has been investigated at 4.2 K where Dy is in the
      ferromagnetic state. In addition to the usual variation of the conductance while
      breaking the wire mechanically, the conductance can be changed reproducibly by
      variation of the magnetic field H, due to the large magnetostriction of Dy. For a
      number of contacts, we observe discrete changes in G(H) in the range of several
      G(0) = 2e(2)/h. The behavior of G(H) and its angular dependence can be
      quantitatively understood by taking into account the magnetostrictive properties
      of Dy. This realization of a magnetostrictive few-atom switch demonstrates the
      possibility of reproducibly tuning the conductance of magnetic nanocontacts by a
      magnetic field.

PMID- 21171602
TI  - Effect of growth orientation and diameter on the elasticity of GaN nanowires. A
      combined in situ TEM and atomistic modeling investigation.
AB  - We characterized the elastic properties of GaN nanowires grown along different
      crystallographic orientations. In situ transmission electron microscopy tensile
      tests were conducted using a MEMS-based nanoscale testing system. Complementary
      atomistic simulations were performed using density functional theory and
      molecular dynamics. Our work establishes that elasticity size dependence is
      limited to nanowires with diameters smaller than 20 nm. For larger diameters, the
      elastic modulus converges to the bulk values of 300 GPa for c-axis and 267 GPa
      for a- and m-axis.

PMID- 21171603
TI  - Generation-dependent molecular recognition controls self-assembly in
      supramolecular dendron-virus complexes.
AB  - In this work molecular dynamics simulation identifies a clear link between the
      dendron-virus multivalent molecular recognition and the nature of the consequent
      self-assembly. Data demonstrate how a weak hydrophobic association is transformed
      in an electrostatic self-assembly, orders of magnitude stronger, depending on the
      dendron generation used to assemble the viruses. This opens a new frontier in the
      engineering of hierarchical self-assemblies, potentially enabling the control of
      the supramolecular properties by acting at the single-molecule level.

PMID- 21171604
TI  - Pore filling of nanostructured electrodes in dye sensitized solar cells by
      initiated chemical vapor deposition.
AB  - The dye sensitized solar cell (DSSC) operation depends on a liquid electrolyte.
      To achieve better performance, the liquid should be replaced with a solid or gel
      electrolyte, e.g., polymers. Here, we demonstrate initiated chemical vapor
      deposition as an effective liquid-free means for in situ polymerization and pore
      filling. We achieve complete pore filling of 12 MUm thick titania resulting in
      enhanced cell performance that is attributed to reduced charge recombination at
      the electrolyte-electrode interface.

PMID- 21171605
TI  - Biosynthesis of HSAF, a tetramic acid-containing macrolactam from Lysobacter
      enzymogenes.
AB  - HSAF was isolated from Lysobacter enzymogenes , a bacterium used in the
      biological control of fungal diseases of plants. Structurally, it is a tetramic
      acid-containing macrolactam fused to a tricyclic system. HSAF exhibits a novel
      mode of action by disrupting sphingolipids important to the polarized growth of
      filamentous fungi. Here we describe the HSAF biosynthetic gene cluster, which
      contains only a single-module polyketide synthase/nonribosomal peptide synthetase
      (PKS/NRPS), although the biosynthesis of HSAF apparently requires two separate
      polyketide chains that are linked together by one amino acid (ornithine) via two
      amide bonds. Flanking the PKS/NRPS are six genes that encoding a cascade of four
      tightly clustered redox enzymes on one side and a sterol desaturase/fatty acid
      hydroxylase and a ferredoxin reductase on the other side. The genetic data
      demonstrate that the four redox genes, in addition to the PKS/NRPS gene and the
      sterol desaturase/fatty acid hydroxylase gene, are required for HSAF production.
      The biochemical data show that the adenylation domain of the NRPS specifically
      activates L-ornithine and that the four-domain NRPS is able to catalyze the
      formation of a tetramic acid-containing product from acyl-S-ACP and ornithinyl-S
      NRPS. These results reveal a previously unrecognized biosynthetic mechanism for
      hybrid PK/NRP in prokaryotic organisms.

PMID- 21171607
TI  - Catalytic silicon-mediated carbon-carbon bond-forming reactions of unactivated
      amides.
AB  - In the presence of catalytic amounts of trialkylsilyl triflate and triethylamine,
      unactivated amides react with imines to afford the corresponding Mannich-type
      adducts in high yields with high anti selectivities. While silicon enolates have
      been widely used in organic synthesis for four decades, this is the first example
      of the catalytic use of the silicon species, to the best of our knowledge.
      Moreover, it is noteworthy that unactivated simple amides bearing alpha-protons
      that are less acidic than those of ketones and aldehydes can be successfully used
      in catalytic direct-type addition reactions. Finally, a preliminary trial of an
      asymmetric catalytic version was conducted and showed promising
      enantioselectivity of the desired product.

PMID- 21171606
TI  - Metal-substituted protein MRI contrast agents engineered for enhanced relaxivity
      and ligand sensitivity.
AB  - Engineered metalloproteins constitute a flexible new class of analyte-sensitive
      molecular imaging agents detectable by magnetic resonance imaging (MRI), but
      their contrast effects are generally weaker than synthetic agents. To augment the
      proton relaxivity of agents derived from the heme domain of cytochrome P450 BM3
      (BM3h), we formed manganese(III)-containing proteins that have higher electron
      spin than their native ferric iron counterparts. Metal substitution was achieved
      by coexpressing BM3h variants with the bacterial heme transporter ChuA in
      Escherichia coli and supplementing the growth medium with Mn3+-protoporphyrin IX.
      Manganic BM3h variants exhibited up to 2.6-fold higher T1 relaxivities relative
      to native BM3h at 4.7 T. Application of ChuA-mediated porphyrin substitution to a
      collection of thermostable chimeric P450 domains resulted in a stable, high
      relaxivity BM3h derivative displaying a 63% relaxivity change upon binding of
      arachidonic acid, a natural ligand for the P450 enzyme and an important component
      of biological signaling pathways. This work demonstrates that protein-based MRI
      sensors with robust ligand sensitivity may be created with ease by including
      metal substitution among the toolkit of methods available to the protein
      engineer.

PMID- 21171608
TI  - Regioselective formation of 2,5-disubstituted oxazoles via copper(I)-catalyzed
      cycloaddition of acyl azides and 1-alkynes.
AB  - The reaction of 1-alkynes with acyl azides in the presence of
      [Tpm(*,Br)Cu(NCMe)]BF(4) [Tpm(*,Br) = tris(3,5-dimethyl-4-bromopyrazolyl)methane]
      as the catalyst provides 2,5-oxazoles in moderate to high yields. This is a novel
      transformation of the CuAAC type that constitutes a significant variation of the
      commonly observed [3 + 2] cycloaddition reaction to yield 1,2,3-triazoles.

PMID- 21171609
TI  - Selective dispersion of single-walled carbon nanotubes with specific chiral
      indices by poly(N-decyl-2,7-carbazole).
AB  - Physico-chemical methods to sort single-walled carbon nanotubes (SWNTs) by chiral
      index are presently lacking but are required for in-depth experimental analysis
      and also for potential future applications of specific species. Here we report
      the unexpected selectivity of poly(N-decyl-2,7-carbazole) to almost exclusively
      disperse semiconducting SWNTs with differences of their chiral indices (n - m) >=
      2 in toluene. The observed selectivity complements perfectly the dispersing
      features of the fluorene analogue poly(9,9-dialkyl-2,7-fluorene), which disperses
      semiconducting SWNTs with (n - m) <= 2 in toluene. The dispersed samples are
      further purified by density gradient centrifugation and analyzed by
      photoluminescence excitation spectroscopy. All-atom molecular modeling with
      decamer model compounds of the polymers and (10,2) and (7,6) SWNTs suggests
      differences in the pi-pi stacking interaction as origin of the selectivity. We
      observe energetically favored complexes between the (10,2) SWNT and the carbazole
      decamer and between the (7,6) SWNT and the fluorene decamer, respectively. These
      findings demonstrate that subtle structural changes of polymers lead to selective
      solvation of different families of carbon nanotubes. Furthermore, chemical
      screening of closely related polymers may pave the way toward simple, low-cost,
      and index-specific isolation of SWNTs.

PMID- 21171610
TI  - Retroviral display in gene therapy, protein engineering, and vaccine development.
AB  - The display and analysis of proteins expressed on biological surfaces has become
      an attractive tool for the study of molecular interactions in enzymology, protein
      engineering, and high-throughput screening. Among the growing number of
      established display systems, retroviruses offer a unique and fully mammalian
      platform for the expression of correctly folded and post-translationally modified
      proteins in the context of cell plasma membrane-derived particles. This is of
      special interest for therapeutic applications such as gene therapy and vaccine
      development and also offers advantages for the engineering of mammalian proteins
      toward customized binding affinities and catalytic activities. This review
      critically summarizes the basic concepts and applications of retroviral display
      and analyses its benefits in comparison to other display techniques.

PMID- 21171611
TI  - Surface iron inhibits quartz-induced cytotoxic and inflammatory responses in
      alveolar macrophages.
AB  - The mechanism of enhancement/inhibition of quartz toxicity induced by iron is
      still unclear. Here the amount of iron on a fibrogenic quartz (Qz) was increased
      by wet impregnation (Fe(NO(3))(3) 0.67 and 6.7 wt %). X-ray diffraction (XRD),
      XRF diffuse reflectance, UV-vis, and infrared (IR) spectroscopies revealed
      dispersed ferric ions, and hematite aggregates at the higher loading. Surface
      features relevant to pathogenicity and cell responses were compared not only to
      the original quartz but also to reference quartz DQ12. Surface charge (zeta
      potential) was more negative on the original and low-loaded specimen than on the
      high-loaded one. DQ12 had a less negative zeta-potential than Qz, ascribed to the
      absence of aluminium present in Qz (1.7 wt %). All quartz specimens were able to
      generate HO(*) radicals, iron-loaded samples being more reactive than original
      quartz. Iron deposition inhibited the rupture of a C-H bond. All quartzes were
      phagocytized by alveolar macrophages (AMPhi cell line NR8383) to the same extent,
      irrespective of their surface state. Conversely, iron loading increased AMPhi
      viability (evaluated by cytotoxicity and induction of apoptosis). Qz was found to
      be much less cytotoxic than DQ12. The induction of oxidative stress and
      inflammatory responses (evaluated by HO-1 mRNA expression and TNF-alpha mRNA and
      protein expression) revealed a reduction in inflammogenicity upon iron loading
      and a more inflammogenic potency of DQ12 ascribed to undissociated SiOH
      interacting via H-bonding with cell membrane components. The results suggest that
      besides aluminium also iron at the quartz surface may have an inhibitory effect
      on adverse health responses.

PMID- 21171613
TI  - Formation of wurtzite InP nanowires explained by liquid-ordering.
AB  - We report an in situ surface X-ray diffraction study of liquid AuIn metal alloys
      in contact with zinc-blende InP (111)(B) substrates at elevated temperatures. We
      observe strong layering of the liquid metal alloy in the first three atomic
      layers in contact with the substrate. The first atomic layer of the alloy has a
      higher indium concentration than in bulk. In addition, in this first layer we
      find evidence for in-plane ordering at hollow sites, which could sterically
      hinder nucleation of zinc-blende InP. This can explain the typical formation of
      the wurtzite crystal structure in InP nanowires grown from AuIn metal particles.

PMID- 21171614
TI  - Discovery of 7-N-piperazinylthiazolo[5,4-d]pyrimidine analogues as a novel class
      of immunosuppressive agents with in vivo biological activity.
AB  - Herein we describe the synthesis and in vitro and in vivo activity of
      thiazolo[5,4-d]pyrimidines as a novel class of immunosuppressive agents, useful
      for preventing graft rejection after organ transplantation. This research
      resulted in the discovery of a series of compounds with potent activity in the
      mixed lymphocyte reaction (MLR) assay, which is well-known as the in vitro model
      for in vivo rejection after organ transplantation. The most potent congeners
      displayed IC(50) values of less than 50 nM in this MLR assay and hence are
      equipotent to cyclosporin A, a clinically used immunosuppressive drug. One
      representative of this series was further evaluated in a preclinical animal model
      of organ transplantation and showed excellent in vivo efficacy. It validates
      these compounds as new promising immunosuppressive drugs.

PMID- 21171615
TI  - Topological ring currents in the "empty" ring of benzo-annelated perylenes.
AB  - Cyclic conjugation in benzo-annelated perylenes is examined by means of the
      topological pi-electron ring currents calculated for each of their constituent
      rings, in a study that is an exact analogy of a recent investigation by Gutman et
      al. based on energy-effect values for the corresponding rings in each of these
      structures. "Classical" approaches, such as Kekule structures, Clar "sextet"
      formulas, and circuits of conjugation, predict that the central ring in perylene
      is "empty" and thus contributes negligibly to cyclic conjugation. However,
      conclusions from the present calculations of topological ring currents agree
      remarkably with those arising from the earlier study involving energy-effect
      values in that, contrary to what would be predicted from the classical
      approaches, rings annelated in an angular fashion relative to the central ring of
      these perylene structures materially increase the extent of that ring's
      involvement in cyclic conjugation. It is suggested that such close quantitative
      agreement between the predictions of these two superficially very different
      indices (energy effect and topological ring current) might be due to the fact
      that, ultimately, both depend, albeit in ostensibly quite different ways, only on
      an adjacency matrix that contains information about the carbon-carbon
      connectivity of the conjugated system in question.

PMID- 21171616
TI  - Bottom-up Assembly of RNA Arrays and Superstructures as Potential Parts in
      Nanotechnology.
AB  - DNA and protein have been extensively scrutinized for feasibility as parts in
      nanotechnology, but another natural building block, RNA, has been largely
      ignored. RNA can be manipulated to form versatile shapes, thus providing an
      element of adaptability to DNA nanotechnology, which is predominantly based upon
      a double-helical structure. The DNA-packaging motor of bacterial virus phi29
      contains six DNA-packaging RNAs (pRNA), which together form a hexameric ring via
      loop/loop interaction. Here we report that this pRNA can be redesigned to form a
      variety of structures and shapes, including twins, tetramers, rods, triangles,
      and 3D arrays several microns in size via interaction of programmed helical
      regions and loops. Three dimensional RNA array formation required a defined
      nucleotide number for twisting of the interactive helix and a palindromic
      sequence. Such arrays are unusually stable and resistant to a wide range of
      temperatures, salt concentrations, and pH.

PMID- 21171617
TI  - Performance of quantum chemically derived charges and persistence of ion cages in
      ionic liquids. A molecular dynamics simulations study of 1-n-butyl-3
      methylimidazolium bromide.
AB  - We carried out classical molecular dynamics simulations with a standard and two
      quantum chemistry based charge sets to study the ionic liquid 1-n-butyl-3
      methylimidazolium bromide, [C(4)C(1)im][Br]. We split the cation up into
      different charge groups and found that the total charge and the charge
      distribution in the imidazolium ring are completely different in the three
      systems while the total charge of the butyl chain is much better conserved
      between the methods. For comparison, the spatial distribution functions and the
      radial distribution functions as well as different time correlation functions
      were calculated. For the structural properties we obtained a good agreement
      between the standard and one of the two quantum chemistry based sets, while the
      results from the second quantum chemistry based set led to a completely different
      picture. The opposite was observed for the dynamic properties, which agree well
      between the standard set and the second quantum chemistry based set, whereas the
      dynamics in the first charge set obtained by quantum chemistry calculations
      proceeded much too slow, which is not obvious from the total charge. We observed,
      that the structure of the butyl chain is mostly unaffected by the choice of the
      charge set. This is an indirect proof for separation into ionic parts and
      nonpolar domains. A second focus of the article is the investigation of dynamical
      heterogeneity and the ion cages. Therefore, we analyzed the reorientational
      dynamics in the three systems and at five different temperatures in system with
      the standard charge set. Generally speaking, we detected four different time
      domains. The fastest movement can be found for the continuous hydrogen bond and
      the nearest neighbor ion pair dynamics. In the second time domain the movement of
      the butyl chain took place. The third time domain consisted in the increasing
      movement of the imidazolium ring as well as in the continuous distortion of an
      ion cage, i.e., the departure of one of the several counterions from the central
      ion's first shell, and the intermittent hydrogen bond dynamics. The remaining
      domain involves the translational displacement of the ions.

PMID- 21171619
TI  - Potent antitumor mimetics of annonaceous acetogenins embedded with an aromatic
      moiety in the left hydrocarbon chain part.
AB  - Annonaceous acetogenins are a large family of naturally occurring polyketides
      exhibiting remarkable anticancer activities. The first generation of annonaceous
      acetogenin mimetic (1, AA005) exhibits comparable activity as that of natural
      products and presents much higher selectivity between cancer and normal cells. In
      this work, we report the design, synthesis, and evaluation of a new series of
      compound 1 analogues in which a variety of conformation-constrained fragments
      were embedded in the left hydrocarbon chain part. Compound 7 bearing a biphenyl
      moiety was identified to exhibit more potent antiproliferative activity and
      preferentially target cancer cells over normal cells and thus represents a new
      lead for further optimization.

PMID- 21171618
TI  - Design, synthesis, and in vitro transfection biology of novel tocopherol based
      monocationic lipids: a structure-activity investigation.
AB  - Herein, we report on the design, synthesis, and in vitro gene delivery efficacies
      of five novel tocopherol based cationic lipids (1-5) in transfecting CHO, B16F10,
      A-549, and HepG2 cells. The in vitro gene transfer efficiencies of lipids (1-5)
      were evaluated by both beta-galactosidase reporter gene expression and inverted
      fluorescent microscopic experiments. The results of the present structure
      activity investigation convincingly demonstrate that the tocopherol based lipid
      with three hydroxyl groups in its headgroup region showed 4-fold better
      transfection efficiency than the commercial formulation. The results also
      demonstrate that these tocopherol based lipids may be targeted to liver.
      Transfection efficiency of all the relevant lipids was maintained even when the
      serum was present during the transfection conditions. The results indicated that
      the designed systems are quite capable of transferring the DNA into all four
      types of cells studied with low or no toxicity.

PMID- 21171620
TI  - DNA compaction by a dendrimer.
AB  - At physiological pH, a PAMAM dendrimer is positively charged and can effectively
      bind negatively charged DNA. Currently, there has been great interest in
      understanding this complexation reaction both for fundamental (as a model for
      complex biological reactions) as well as for practical (as a gene delivery
      material and probe for sensing DNA sequence) reasons. Here, we have studied the
      complexation between double-stranded DNA (dsDNA) and various generations of PAMAM
      dendrimers (G3-G5) through atomistic molecular dynamics simulations in the
      presence of water and ions. We report the compaction of DNA on a nanosecond time
      scale. This is remarkable, given the fact that such a short DNA duplex with a
      length close to 13 nm is otherwise thought to be a rigid rod. Using several
      nanoseconds long MD simulations, we have observed various binding modes of dsDNA
      and dendrimers for various generations of PAMAM dendrimers at varying charge
      ratios, and it confirms some of the binding modes proposed earlier. The binding
      is driven by the electrostatic interaction, and the larger the dendrimer charge,
      the stronger the binding affinity. As DNA wraps/binds to the dendrimer,
      counterions originally condensed onto DNA (Na+) and the dendrimer (Cl(-)) get
      released. We calculate the entropy of counterions and show that there is gain in
      entropy due to counterion release during the complexation. MD simulations
      demonstrate that, when the charge ratio is greater than 1 (as in the case of the
      G5 dendrimer), the optimal wrapping of DNA is observed. Calculated binding
      energies of the complexation follow the trend G5 > G4 > G3, in accordance with
      the experimental data. For a lower-generation dendrimer, such as G3, and, to some
      extent, for G4 also, we see considerable deformation in the dendrimer structure
      due to their flexible nature. We have also calculated the various helicoidal
      parameters of DNA to study the effect of dendrimer binding on the structure of
      DNA. The B form of the DNA is well preserved in the complex, as is evident from
      various helical parameters, justifying the use of the PAMAM dendrimer as a
      suitable delivery vehicle.

PMID- 21171621
TI  - Data variance and statistical significance in 2D-gel electrophoresis and DIGE
      experiments: comparison of the effects of normalization methods.
AB  - Identifying changes in the relative abundance of proteins between different
      biological samples is often confounded by technical noise. In this work, we
      compared eight normalization methods commonly used in two-dimensional gel
      electrophoresis and difference gel electrophoresis (DIGE) experiments for their
      ability to reduce noise and for their influence on the list of proteins whose
      difference in abundance between two samples is determined to be statistically
      significant. With respect to reducing noise we find that, while all methods
      improve upon unnormalized data, cyclic linear normalization is the least well
      suited to gel-based proteomics and the performances of the other methods are
      similar. We also find in DIGE data that the choice of normalization method has
      less of an impact on the noise than does the decision to use an internal
      reference in the experimental design and that both normalization and
      standardization using the internal reference are required to maximally reduce
      variance. Despite the similar noise reduction achieved by most normalization
      methods, the list of proteins whose abundance was determined to differ
      significantly between biological groups differed depending on the choice of
      normalization method. This work provides a direct comparison of the impact of
      normalization methods in the context of common experimental designs.

PMID- 21171622
TI  - Nitrogen contamination of surficial aquifers--a growing legacy.

PMID- 21171623
TI  - Formation of nitrogen-containing oligomers by methylglyoxal and amines in
      simulated evaporating cloud droplets.
AB  - Reactions of methylglyoxal with amino acids, methylamine, and ammonium sulfate
      can take place in aqueous aerosol and evaporating cloud droplets. These processes
      are simulated by drying droplets and bulk solutions of these compounds (at low
      millimolar and 1 M concentrations, respectively) and analyzing the residuals by
      scanning mobility particle sizing, nuclear magnetic resonance, aerosol mass
      spectrometry (AMS), and electrospray ionization MS. The results are consistent
      with imine (but not diimine) formation on a time scale of seconds, followed by
      the formation of nitrogen-containing oligomers, methylimidazole, and
      dimethylimidazole products on a time scale of minutes to hours. Measured
      elemental ratios are consistent with imidazoles and oligomers being major
      reaction products, while effective aerosol densities suggest extensive reactions
      take place within minutes. These reactions may be a source of the light
      absorbing, nitrogen-containing oligomers observed in urban and biomass-burning
      aerosol particles.

PMID- 21171624
TI  - Time-resolved small-angle X-ray scattering studies of polymer-silica
      nanocomposite particles: initial formation and subsequent silica redistribution.
AB  - Small angle X-ray scattering (SAXS) is a powerful characterization technique for
      the analysis of polymer-silica nanocomposite particles due to their relatively
      narrow particle size distributions and high electron density contrast between the
      polymer core and the silica shell. Time-resolved SAXS is used to follow the
      kinetics of both nanocomposite particle formation (via silica nanoparticle
      adsorption onto sterically stabilized poly(2-vinylpyridine) (P2VP) latex in
      dilute aqueous solution) and also the spontaneous redistribution of silica that
      occurs when such P2VP-silica nanocomposite particles are challenged by the
      addition of sterically stabilized P2VP latex. Silica adsorption is complete
      within a few seconds at 20  degrees C and the rate of adsorption strongly
      dependent on the extent of silica surface coverage. Similar very short time
      scales for silica redistribution are consistent with facile silica exchange
      occurring as a result of rapid interparticle collisions due to Brownian motion;
      this interpretation is consistent with a zeroth-order Smoluchowski-type
      calculation.

PMID- 21171625
TI  - Enhancement of spin polarization in a transition metal oxide ferromagnetic
      nanodot diode.
AB  - Enhancement of spin polarization was observed in a transition metal oxide
      (Fe,Zn)(3)O(4)/Nb-SrTiO(3) ferromagnetic nanodot Schottky diode. The highly
      integrated oxide nanodot diodes were constructed using nanoimprint lithography
      based on a Mo lift-off method in combination with a pulsed laser deposition
      technique. The junction magnetoresistance of diodes increased as diode size
      increased. The spin polarization estimated from the thermionic emission model is
      enhanced from P = 0.74 in a conventional film to P = 0.89 in a nanodot diode
      whose size is 300 * 300 nm(2). The nanofabrication technique used here will
      enable us to construct superior transition metal oxide spintronic nanomaterial
      and nanodevices.

PMID- 21171626
TI  - Structure and elemental distribution of (Ga,Mn)N nanowires.
AB  - (Ga,Mn)N nanowires were grown by plasma-assisted molecular beam epitaxy on p-type
      Si(111) substrates. Chemical composition and elemental distribution of single
      nanowires were analyzed by energy dispersive X-ray spectroscopy revealing an
      inhomogeneous Mn distribution decreasing from the surface of the nanowires toward
      the inner core region. The average Mn concentration within the nanowires is found
      to be below 1%. High-resolution transmission electron microscopy shows the
      presence of planar defects perpendicular to the growth direction in undoped and
      Mn-doped GaN nanowires. The density of planar defects dramatically increases
      under Mn supply.

PMID- 21171627
TI  - Efficient and directed Nano-LED emission by a complete elimination of transverse
      electric guided modes.
AB  - A key to the success of solid-state lighting is an ultraefficient light
      extraction, ~90%. Recent advances in nanotechnology, particularly in creating
      nanorods, present an unprecedented opportunity to manipulate optical modes at
      nanometer scales. Here, we report an optically pumped nanorod light-emitting
      diode (LED) with an ultrahigh extraction efficiency of 79% at lambda = 460 nm
      without the use of either a back reflector or thin film technology. We
      demonstrated experimentally three key mechanisms for achieving high efficiency:
      guided mode-reduction, embedded quantum wells, and ultraefficient light out
      coupling by the fundamental HE(11) mode. Furthermore, we show that size reduction
      at nanoscale represents a new degree-of-freedom for alternating and achieving a
      more directed LED emission.

PMID- 21171628
TI  - Fabrication of sub-5 nm nanochannels in insulating substrates using focused ion
      beam milling.
AB  - The use of focused ion beam (FIB) milling to fabricate nanochannels with critical
      dimensions extending below 5 nm is described. FIB milled lines have narrowing
      widths as they are milled deeper into a substrate. This focusing characteristic
      is coupled with a two-layered architecture consisting of a relatively thick (>100
      nm) metal film deposited onto a substrate. A channel is milled through the metal
      layer until it penetrates a prescribed depth into the substrate material. The
      metal is then removed, leaving a nanochannel with smooth surfaces and lateral
      dimensions as small as sub-5 nm. These open nanochannels can be sealed with a
      cover plate and the resulting devices are well-suited for single-molecule DNA
      transport studies. This methodology is used with quartz, single-crystal silicon,
      and polydimethylsiloxane substrates to demonstrate its general utility.

PMID- 21171629
TI  - Heterojunction photovoltaics using GaAs nanowires and conjugated polymers.
AB  - We demonstrate an organic/inorganic solar cell architecture based on a blend of
      poly(3-hexylthiophene) (P3HT) and narrow bandgap GaAs nanowires. The measured
      increase of device photocurrent with increased nanowire loading is correlated
      with structural ordering within the active layer that enhances charge transport.
      Coating the GaAs nanowires with TiO(x) shells passivates nanowire surface states
      and further improves the photovoltaic performance. We find that the P3HT/nanowire
      cells yield power conversion efficiencies of 2.36% under white LED illumination
      for devices containing 50 wt % of TiO(x)-coated GaAs nanowires. Our results
      constitute important progress for the use of nanowires in large area solution
      processed hybrid photovoltaic cells and provide insight into the role of
      structural ordering in the device performance.

PMID- 21171630
TI  - Large-scale graphene transistors with enhanced performance and reliability based
      on interface engineering by phenylsilane self-assembled monolayers.
AB  - In this letter, we report the dielectric/graphene interface physics and
      engineering of large-scale, chemical vapor deposited (CVD) graphene transistors
      by self-assembling a molecular-scale organosilane monolayer onto the dielectric
      surface. We show that phenyl-alkyl-terminated self-assembled monolayers (SAM) at
      the dielectric/graphene interface consistently improve the graphene device
      performance and reliability. The extrinsic field-effect mobility of large-scale
      CVD graphene transistors on the phenyl-SAM engineered dielectric is currently up
      to 2500 cm(2)/(V s) at room temperature, considerably higher than the
      counterparts without the SAM. In addition, significant reduction on the bias
      stress instability and hysteresis is achieved by the SAM-based interface
      engineering. Further analysis reveals that charge injection from graphene to the
      dielectric/graphene interface dominates the observed hysteresis behavior. For
      both graphene transistors with and without SAMs, the bias stress stability, that
      is, Dirac point shift under bias stress, is well described by the stretched
      exponential model with its fitting parameters clearly indicating different
      interface properties.

PMID- 21171631
TI  - Better than 10 mA field emission from an isolated structure emitter of a metal
      oxide/CNT composite.
AB  - An isolated structure emitter is presented that can deliver a field emission
      better than 10 mA, a level that is by far the highest ever reported. A composite
      of CNT (carbon nanotube) and WO(3) is used to grow the point emitter by a crystal
      like growth technique. The head of the grown needle that is the emitter is
      removed by electric discharge machining (EDM). The EDM treatment not only
      controls the length of the emitter as desired but also makes the tip of the
      emitter uniform. The thermal heat due to EDM treatment leads to the formation of
      a tungsten carbide phase, which results in a 3 orders of magnitude reduction in
      contact resistance. The point emitter is robust in its stability, as evidenced by
      its on-time resilience against a severe bias test.

PMID- 21171632
TI  - Controlled growth of ordered nanopore arrays in GaN.
AB  - High-quality, ordered nanopores in semiconductors are attractive for numerous
      biological, electrical, and optical applications. Here, GaN nanorods with
      continuous pores running axially through their centers were grown by
      organometallic vapor phase epitaxy. The porous nanorods nucleate on an underlying
      (0001)-oriented GaN film through openings in a SiN(x) template that are milled by
      a focused ion beam, allowing direct placement of porous nanorods. Nanopores with
      diameters ranging from 20-155 nm were synthesized with crystalline sidewalls.

PMID- 21171633
TI  - Thermopower of amine-gold-linked aromatic molecular junctions from first
      principles.
AB  - Using a self-energy corrected scattering-state approach based on density
      functional theory (DFT), we explain recent measurements of the thermopower or the
      Seebeck coefficient, S, for oligophenyldiamine-gold single-molecule junctions and
      show that they are consistent with separate measurements of their electrical
      conductance, G. Our calculations with self-energy corrections to the DFT
      electronic states in the junction predict low-bias S and G values in good
      quantitative agreement with experiments. We find S varies linearly with the
      number of phenyls N, with a gradient beta(S) of 2.1 MUV/K, in excellent agreement
      with experiment. In contrast, DFT calculations without self-energy corrections
      overestimate both S and beta(S) (with a DFT value for beta(S) three times too
      large). While beta(S) is found to be a robust quantity independent of junction
      geometry, the computed values of S show significant sensitivity to the contact
      atomic structure-more so than the computed values of G. This observation is
      consistent with the experimentally measured spreads in S and G for amine-Au
      junctions. Taken together with previous computations of the electrical
      conductance (as reported in Quek, S. Y.; et al., Nano Lett. 2009, 9, 3949), our
      calculations of S conclusively demonstrate, for the first time, the consistency
      of two complementary yet distinct measurements of charge transport through single
      molecule junctions and substantiate the need for an accurate treatment of
      junction electronic level alignment to describe off-resonant tunneling in these
      junctions.

PMID- 21171634
TI  - Palladium-catalyzed cross-coupling of polyfluoroarenes with simple arenes.
AB  - The most efficient method to construct biaryls is the direct dehydrogenative
      cross-coupling of two different aromatic rings. Such an ideal cross arylation
      starting from distinct polyfluoroarenes and simple arenes was presented. The
      selectivity of the cross-coupling was controlled by both of the electronic
      property of fluoroarenes and steric hindrance of simple arenes. Diisopropyl
      sulfide was essential to promote the efficacy.

PMID- 21171635
TI  - Nondestructive ion trap mass analysis at high pressure.
AB  - A method for performing nondestructive ion trap mass analysis at high pressures
      (>1 mTorr) has been developed using image current measurement with constant
      dipolar excitation. Instead of monitoring the ion secular motion, a harmonic of
      the ion motion was used for narrow band image current measurement followed by
      Fourier Transform. The capability of this technique has been demonstrated with
      mass analysis using a single measurement at pressures of 10 mTorr or higher.
      Methods for mixture analysis and tandem mass spectrometry have also been
      developed for nondestructive mass analysis.

PMID- 21171636
TI  - Precise color tuning via hybrid light-emitting electrochemical cells.
AB  - We report color-tunable light-emitting devices employing CdSe/ZnS quantum dots
      (QDs) blended into a polymer light-emitting electrochemical cell (LEC)
      architecture. This novel structure circumvents the charge-tunneling barrier of
      QDs to achieve bright, uniform, and highly voltage-independent
      electroluminescence, with nearly all emission generated by the QDs. By blending
      varying ratios of two QD materials that emit at different wavelengths, we
      demonstrate precise color control in a single layer device structure.

PMID- 21171637
TI  - The ultimate fate of supercooled liquids.
AB  - In recent years it has become widely accepted that a dynamical length scale
      xi(alpha) plays an important role in supercooled liquids near the glass
      transition. We examine the implications of the interplay between the growing
      xi(alpha) and the size of the crystal nucleus, xi(M), which shrinks on cooling.
      We argue that at low temperatures where xi(alpha) > xi(M) a new crystallization
      mechanism emerges, enabling rapid development of a large scale web of sparsely
      connected crystallinity. Though we predict this web percolates the system at too
      low a temperature to be easily seen in the laboratory, there are noticeable
      residual effects near the glass transition that can account for several
      previously observed unexplained phenomena of deeply supercooled liquids including
      Fischer clusters and anomalous crystal growth near T(g).

PMID- 21171639
TI  - Emulsification through surfactant hydration: the PIC process revisited.
AB  - We have performed sudden composition changes on a (surfactant + oil + water)
      system by adding water to a (surfactant + oil) solution. This composition change
      quenches the system into a metastable oil-in-water emulsion with a population in
      the 100 nm range. The conditions for a successful quench are as follows: the
      initial water content should be below a boundary called the "clearing boundary"
      (CB), the final water content should be sufficiently beyond CB, and the quench
      should be fast. We have used high purity components to avoid the complex phase
      separation patterns that occur with low purity ingredients: the surfactant is
      octaethylenehexadecyl ether (C(16)E(8)) and the oil is hexadecane (C(16)). Under
      these conditions, we show that the pathway for this type of quench proceeds
      through the swelling of the reverse micellar phase by the added water and the
      formation of a sponge phase. Then, further water addition causes the nucleation
      of oil droplets in this sponge phase, with a size that matches the spontaneous
      curvature of the sponge phase. Part of the surfactant remains adsorbed on these
      droplets, and the rest is expelled as micelles that coexist with the droplets. It
      is concluded that a PIC emulsification will always lead to a bimodal size
      distribution with surfactant "wasted" in small micelles. This is in contrast with
      the more efficient PIT emulsification.

PMID- 21171638
TI  - Structure of the metal-dependent deacetylase LpxC from Yersinia enterocolitica
      complexed with the potent inhibitor CHIR-090 .
AB  - The first committed step of lipid A biosynthesis is catalyzed by UDP-(3-O-((R)-3
      hydroxymyristoyl))-N-acetylglucosamine deacetylase, a metal-dependent deacetylase
      also known as LpxC. Because lipid A is essential for bacterial viability, the
      inhibition of LpxC is an appealing therapeutic strategy for the treatment of Gram
      negative bacterial infections. Here we report the 1.79 A resolution X-ray crystal
      structure of LpxC from Yersinia enterocolitica (YeLpxC) complexed with the potent
      hydroxamate inhibitor CHIR-090. This enzyme is a nearly identical orthologue of
      LpxC from Yersinia pestis (99.7% sequence identity), the pathogen that causes
      bubonic plague. Similar to the inhibition of LpxC from Escherichia coli, CHIR-090
      inhibits YeLpxC via a two-step slow, tight-binding mechanism with an apparent
      K(i) of 0.54 +/- 0.14 nM followed by conversion of the E.I to E.I* species with a
      rate constant of 0.11 +/- 0.01 min(-1). The structure of the LpxC complex with
      CHIR-090 shows that the inhibitor hydroxamate group chelates the active site zinc
      ion, and the "tail" of the inhibitor binds in the hydrophobic tunnel in the
      active site. This hydrophobic tunnel is framed by a betaalphabeta subdomain that
      exhibits significant conformational flexibility as it accommodates inhibitor
      binding. CHIR-090 displays a 27 mm zone of inhibition against Y. enterocolitica
      in a Kirby-Bauer antibiotic assay, which is comparable to its reported activity
      against other Gram-negative species including E. coli and Pseudomonas aeruginosa.
      This study demonstrates that the inhibition of LpxC should be explored as a
      potential therapeutic and/or prophylatic response to infection by weaponized
      Yersinia species.

PMID- 21171640
TI  - Single and multi-exciton dynamics in aqueous protochlorophyllide aggregates.
AB  - In plants, the oxidoreductase enzyme POR reduces protochlorophyllide (Pchlide)
      into chlorophyllide (Chlide), using NADPH as a cofactor. The reduction involves
      the transfer of two electrons and two protons to the C17?C18 double bond of
      Pchlide, and the reaction is initiated by the absorption of light by Pchlide
      itself. In this work we have studied the excited state dynamics of Pchlide
      dissolved in water, where it forms excitonically coupled aggregates, by ultrafast
      time-resolved transient absorption and fluorescence experiments performed in the
      480-720 nm visible region and in the 1780-1590 cm(-1) mid-IR region. The ground
      state visible absorption spectrum of aqueous Pchlide red shifts and broadens in
      comparison to the spectrum of monomeric Pchlide in organic solvents. The
      population of the one-exciton state occurs at low excitation densities, of <1
      photon per aggregate. We characterized the multiexciton manifolds spectra by
      measuring the absorption difference spectra at increasingly higher photon
      densities. The multiexciton states are characterized by blue-shifted stimulated
      emission and red-shifted excited state absorption in comparison to those of the
      one-exciton manifold. The relaxation dynamics of the multiexciton manifolds into
      the one-exciton manifold is found to occur in ~10 ps. This surprisingly slow rate
      we suggest is due to the intrinsic charge transfer character of the PChlide
      excited state that leads to solvation, stabilizing the CT state, and subsequent
      charge recombination, which limits the exciton relaxation.

PMID- 21171641
TI  - Controlling nonclassical content of clathrate hydrates through the choice of
      molecular guests and temperature.
AB  - Low-temperature, low-pressure studies of clathrate hydrates (CHs) have revealed
      that small ether and other proton-acceptor guests greatly enhance rates of
      clathrate hydrate nucleation and growth; rapid formation and transformations are
      enabled at temperatures as low as 110 K, and cool moist vapors containing small
      ether molecules convert to mixed-gas CHs on a subsecond time scale. More
      recently, FTIR spectroscopic studies of the tetrahydrofuran (THF)-HCN double
      clathrate hydrate revealed a sizable frequency shift accompanied by a four-fold
      intensification of the C-N stretch-mode absorption of the small cage HCN,
      behavior that is enhanced by cooling and which correlates precisely with similar
      significant changes of the ether C-O/C-C stretch modes. These temperature
      dependent correlated changes in the infrared spectra have been attributed to
      equilibrated extensive hydrogen bonding of neighboring large- and small-cage
      guest molecules with water molecules of the intervening wall. An ether guest
      functions as a proton acceptor, particularly so when complemented by the action
      of a proton-donor (HCN)/electron-acceptor (SO(2)) small-cage guest. Because guest
      molecules of the classic clathrate hydrates do not participate in hydrogen bonds
      with the host water, this H-bonding of guests has been labeled "nonclassical".
      The present study has been enriched by comparing observed FTIR spectra with high
      level molecular orbital computational results for guests and hydrogen-bonded
      guest-water dimers. Vibrational frequency shifts, from heterodimerization of
      ethers and water, correlate well with the corresponding observed classical to
      nonclassical shifts. The new spectroscopic data reveal that the nonclassical
      structures can contribute at observable levels to CH infrared spectra for a
      remarkable range of temperatures and choice of guest molecules. By the choice of
      guest molecules, it is now possible to select the abundance levels of
      nonclassical configurations, ranging from ~0 to 100%, for a given temperature.
      This ability is expected to hasten understanding of the role of guest-induced
      nonclassical structures in the acceleration or inhibition of the rates of CH
      formation and transformation.

PMID- 21171642
TI  - From hollow olive-shaped BiVO4 to n-p core-shell BiVO4@Bi2O3 microspheres:
      controlled synthesis and enhanced visible-light-responsive photocatalytic
      properties.
AB  - In this study, hollow olive-shaped BiVO(4) and n-p core-shell BiVO(4)@Bi(2)O(3)
      microspheres were synthesized by a novel sodium bis(2-ethylhexyl)sulfosuccinate
      (AOT)-assisted mixed solvothermal route and a thermal solution of NaOH etching
      process under hydrothermal conditions for the first time, respectively. The as
      obtained products were characterized by X-ray diffraction (XRD), scanning
      electron microscopy (SEM), transmission electron microscopy, Brunauer-Emmett
      Teller surface area, and UV-vis diffuse-reflectance spectroscopy in detail. The
      influence of AOT and solvent ratios on the final products was studied. On the
      basis of SEM observations and XRD analyses of the samples synthesized at
      different reaction stages, the formation mechanism of hollow olive-shaped BiVO(4)
      microspheres was proposed. The photocatalytic activities of hollow olive-shaped
      BiVO(4) and core-shell BiVO(4)@Bi(2)O(3) microspheres were evaluated on the
      degradation of rhodamine B under visible-light irradiation (lambda > 400 nm). The
      results indicated that core-shell BiVO(4)@Bi(2)O(3) exhibited much higher
      photocatalytic activities than pure olive-shaped BiVO(4). The mechanism of
      enhanced photocatalytic activity of core-shell BiVO(4)@Bi(2)O(3) microspheres was
      discussed on the basis of the calculated energy band positions as well. The
      present study provides a new strategy to enhancing the photocatalytic activity of
      visible-light-responsive Bi-based photocatalysts by p-n heterojunction.

PMID- 21171643
TI  - Photophysical properties of a series of electron-donating and -withdrawing
      platinum acetylide two-photon chromophores.
AB  - To explore spectroscopic structure-property relationships in platinum acetylides,
      we synthesized a series of complexes having the molecular formula trans
      bis(tributylphosphine)-bis(4-((9,9-diethyl-7-ethynyl-9H-fluoren-2-yl)ethynyl)-R)
      platinum. The substituent, R = NH(2), OCH(3), N(phenyl)(2), t-butyl, CH(3), H, F,
      benzothiazole, CF(3), CN, and NO(2), was chosen for a systematic variation in
      electron-donating and -withdrawing properties as described by the Hammett
      parameter sigma(p). UV/vis, fluorescence, and phosphorescence spectra, transient
      absorption spectra on the fs-ps time scale, and longer time scale flash
      photolysis on the ns time scale were collected. DFT and TDDFT calculations of the
      T(1) and S(1) energies were performed. The E(S) and E(T) values measured from
      linear spectra correlate well with the calculated results, giving evidence for
      the delocalized MLCT character of the S(1) state and confinement of the T(1)
      exciton on one ligand. The calculated T(1) state dipole moment ranges from 0.5 to
      14 D, showing the polar, charge-transfer character of the T(1) state. The
      ultrafast absorption spectra have broad absorption bands from 575 to 675 nm and
      long wavelength contribution, which is shown from flash photolysis measurements
      to be from the T(1) state. The T(1) energy obtained from phosphorescence, the
      T(1)-T(n) transition energy obtained from flash photolysis measurements, and the
      triplet-state radiative rate constant are functions of the calculated spin
      density distribution on the ligand. The calculations show that the triplet
      exciton of chromophores with electron-withdrawing substituents is localized away
      from the central platinum atom, red-shifting the spectra and increasing the
      triplet-state lifetime. Electron-donating substituents have the opposite effect
      on the location of the triplet exciton, the spectra, and the triplet-state
      lifetime. The relation between the intersystem crossing rate constant and the
      S(1)-T(1) energy gap shows a Marcus relationship with a reorganization energy of
      0.83 eV. The calculations show that intersystem crossing occurs by conversion
      from a nonpolar, delocalized S(1) state to a polar, charge-transfer T(1) state
      confined to one ligand, accompanied by conformation changes and charge transfer,
      supporting the experimental evidence for Marcus behavior.

PMID- 21171644
TI  - Preparation of catalytically active, covalent alpha-polylysine-enzyme conjugates
      via UV/vis-quantifiable bis-aryl hydrazone bond formation.
AB  - Covalent UV/vis-quantifiable bis-aryl hydrazone bond formation was investigated
      for the preparation of conjugates between alpha-poly-d-lysine (PDL) and either
      alpha-chymotrypsin (alpha-CT) or horseradish peroxidase (HRP). PDL and the
      enzymes were first modified via free amino groups with the linking reagents
      succinimidyl 6-hydrazinonicotinate acetone hydrazone (S-HyNic, at pH 7.6) and
      succinimidyl 4-formylbenzoate (S-4FB, at pH 7.2), respectively. The modified PDL
      and enzymes were then conjugated at pH 4.7, whereby polymer chains carrying
      several enzymes were obtained. Kinetics of the bis-aryl hydrazone bond formation
      was investigated spectrophotometrically at 354 nm. Retention of the enzymatic
      activity after conjugate formation was confirmed by using the substrates N
      succinimidyl-l-Ala-l-Ala-l-Pro-l-Phe-p-nitroanilide (for alpha-CT) and 2,2'-azino
      bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS, for HRP).
      Thus, not only a mild and efficient preparation and convenient quantification of
      a conjugate between the polycationic alpha-polylysine and enzymes could be shown,
      but also the complete preservation of the enzymatic activity.

PMID- 21171645
TI  - Conversion of hexagonal Sb2Te3 nanoplates into nanorings driven by growth
      temperature.
AB  - We describe a novel route for the conversion of hexagonal Sb(2)Te(3) nanoplates
      into nanorings driven by growth temperature in a simple solvothermal process. The
      transmission electron microscopy was employed to investigate systemically the
      morphology, size, crystallinity, and microstructure of the as-prepared products.
      The experiments indicated that the growth temperature had a great effect on the
      morphology of antimony telluride nanostructures. When the experiments were
      conducted at 200  degrees C, the hexagonal antimony telluride nanoplates were
      obtained. However, if the experiments were carried out at higher temperature of
      230  degrees C, the hexagonal antimony telluride nanorings were achieved by
      dissolution of the inner part with a higher density of defects of the hexagonal
      nanoplates for the first time. A possible formation mechanism was proposed on the
      basis of experimental results and analysis. This work may open a new rational
      route for the synthesis of the hexagonal antimony telluride nanorings, which may
      have scientific and technological applications in various functional devices.

PMID- 21171646
TI  - High-voltage electrophoretic deposition for vertically aligned forests of one
      dimensional nanoparticles.
AB  - Deposition of aligned forests of 1D nanoparticles (carbon nanotubes and MnO(2)
      nanorods) on conductive, including flexible and transparent, substrates has been
      achieved at room temperature. The process, named high-voltage electrophoretic
      deposition (HVEPD), has been enabled by three key elements: high deposition
      voltage for alignment, low dispersion concentration of the nanoparticles to avoid
      aggregation, and simultaneous formation of a holding layer by electrodeposition.
      The effects of key parameters are investigated. The alignment on the vertical
      direction has been revealed by scanning electron microscopy of the samples, their
      superhydrophobicity, electrochemical performance, and capability to electrically
      connect two separated electrodes. Compared with their randomly oriented
      counterparts, the aligned nanoforests showed higher electrochemical capacitance,
      lower electrical resistance, and the capability to achieve superhydrophobicity,
      implicating their potential in a broad range of applications.

PMID- 21171647
TI  - Nanometer-scale oxide thin film transistor with potential for high-density image
      sensor applications.
AB  - The integration of electronically active oxide components onto silicon circuits
      represents an innovative approach to improving the functionality of novel
      devices. Like most semiconductor devices, complementary-metal-oxide-semiconductor
      image sensors (CISs) have physical limitations when progressively scaled down to
      extremely small dimensions. In this paper, we propose a novel hybrid CIS
      architecture that is based on the combination of nanometer-scale amorphous In-Ga
      Zn-O (a-IGZO) thin-film transistors (TFTs) and a conventional Si photo diode
      (PD). With this approach, we aim to overcome the loss of quantum efficiency and
      image quality due to the continuous miniaturization of PDs. Specifically, the a
      IGZO TFT with 180 nm gate length is probed to exhibit remarkable performance
      including low 1/f noise and high output gain, despite fabrication temperatures as
      low as 200  degrees C. In particular, excellent device performance is achieved
      using a double-layer gate dielectric (Al2O3/SiO2) combined with a trapezoidal
      active region formed by a tailored etching process. A self-aligned top gate
      structure is adopted to ensure low parasitic capacitance. Lastly, three
      dimensional (3D) process simulation tools are employed to optimize the four-pixel
      CIS structure. The results demonstrate how our stacked hybrid device could be the
      starting point for new device strategies in image sensor architectures.
      Furthermore, we expect the proposed approach to be applicable to a wide range of
      micro- and nanoelectronic devices and systems.

PMID- 21171648
TI  - Coverage-dependent formation of chiral ethylthiolate-Au complexes on Au(111).
AB  - We studied the coverage-dependent self-assembly of the flat-lying phase of
      ethylthiolate on Au(111). At low coverage, we observed the formation of short
      stripes of chiral Au-(SC(2)H(5))(2) complexes that arrange in a disordered phase.
      The latter grow partly at the expense of the native Au(111) surface
      reconstruction, which is fully lifted for a coverage of ~0.60 ML. We found that
      the lift of the reconstruction and evaporation from step edges are competing
      adatom sources. Close to saturation coverage (0.70 to 0.75 ML), large, well
      ordered domains with a (8 * ?3)rectangular superstructure formed. Alternation of
      chirality was found in adjacent stripes as already reported for other short
      alkanethiolates. We suggest that, because of a simple geometrical consideration,
      the chirality should, on the contrary, be preserved in the stripe phase of longer
      alkanethiolates.

PMID- 21171649
TI  - A temporal gene delivery system based on fibrin microspheres.
AB  - Combining complementary nonviral gene delivery vehicles such as tissue
      engineering scaffolds and liposomes not only is a promising avenue for
      development of safe and effective gene delivery system but also provides an
      opportunity to design dynamic extended release systems with spatiotemporal
      control. However, the DNA loading capacity of scaffolds such as fibrin is
      limited. Fibrin microspheres carrying DNA complexes can be utilized to extend the
      capacity of fibrin scaffold. Here, in a proof of concept study, the feasibility
      of fibrin microspheres for extending gene delivery capacity is described. Toward
      this goal, fibrin microspheres encapsulating lipoplexes were fabricated. The
      structural and functional integrity of DNA was assessed respectively by gel
      electrophoresis and an in vivo pilot study, using endothelial nitric oxide
      synthase (eNOS) as a model therapeutic gene in a rabbit ear ulcer model of
      compromised wound healing. The results confirmed structural integrity and
      successful delivery and functional integrity, assessed qualitatively by
      angiogenic effect of eNOS. Finally, as a step toward development of a "fibrin in
      fibrin" temporal release system, fibrin microspheres were shown to degrade and
      release DNA differentially compared to fibrin scaffold. It can thus be concluded
      that fibrin microspheres can be utilized for gene delivery to extend the capacity
      of a fibrin scaffold and can form a component of a "fibrin in fibrin" temporal
      release system.

PMID- 21171650
TI  - Organellar Na+/H+ exchangers: novel players in organelle pH regulation and their
      emerging functions.
AB  - Mammalian Na+/H+ exchangers (NHEs) play a fundamental role in cellular ion
      homeostasis. NHEs exhibit an appreciable variation in expression, regulation, and
      physiological function, dictated by their dynamics in subcellular localization
      and/or interaction with regulatory proteins. In recent years, a subgroup of NHEs
      consisting of four isoforms has been identified, and its members predominantly
      localize to the membranes of the Golgi apparatus and endosomes. These organellar
      NHEs constitute a family of transporters with an emerging function in the
      regulation of luminal pH and in intracellular membrane trafficking as expressed,
      for example, in cell polarity development. Moreover, specific roles of a variety
      of cofactors, regulating the intracellular dynamics of these transporters, are
      also becoming apparent, thereby providing further insight into their mechanism of
      action and overall functioning. Interestingly, organellar NHEs have been related
      to mental disorders, implying a potential role in the brain, thus expanding the
      physiological significance of these transporters.

PMID- 21171651
TI  - Platinum(II)-catalyzed generation and [3+2] cycloaddition reaction of alpha,beta
      unsaturated carbene complex intermediates for the preparation of polycyclic
      compounds.
AB  - Pt(II)-catalyzed generation of unsaturated carbene complex intermediates from
      various propargyl ether derivatives based on electrophilic activation of alkynes
      was realized. These in situ generated unsaturated carbene complexes undergo [3+2]
      cycloaddition reaction with various vinyl ethers, leading to efficient formation
      of indoles, naphthols, and benzofuran fused with a five-membered ring in high
      yields.

PMID- 21171652
TI  - Chlorinated benzenes cause concomitantly oxidative stress and induction of
      apoptotic markers in lung epithelial cells (A549) at nonacute toxic
      concentrations.
AB  - In industrialized countries, people spend more time indoors and are therefore
      increasingly exposed to volatile organic compounds that are emitted at working
      places and from consumer products, paintings, and furniture, with chlorobenzene
      (CB) and 1,2-dichlorobenzene (DCB) being representatives of the halogenated
      arenes. To unravel the molecular effects of low concentrations typical for indoor
      and occupational exposure, we exposed human lung epithelial cells to CB and DCB
      and analyzed the effects on the proteome level by 2-D DIGE, where 860 protein
      spots were detected. A set of 25 and 30 proteins were found to be significantly
      altered due to exposure to environmentally relevant concentrations of 10(-2)
      g/m(3) of CB or 10(-3) g/m(3) of DCB (2.2 and 0.17 ppm), respectively. The most
      enriched pathways were cell death signaling, oxidative stress response, protein
      quality control, and metabolism. The involvement of oxidative stress was
      validated by ROS measurement. Among the regulated proteins, 28, for example,
      voltage-dependent anion-selective channel protein 2, PDCD6IP protein, heat shock
      protein beta-1, proliferating cell nuclear antigen, nucleophosmin, seryl-tRNA
      synthetase, prohibitin, and protein arginine N-methyltransferase 1, could be
      correlated with the molecular pathway of cell death signaling. Caspase 3
      activation by cleavage was confirmed for both CB and DCB by immunoblotting.
      Treatment with CB or DCB also caused differential protein phosphorylation, for
      example, at the proteins HNRNP C1/C2, serine-threonine receptor associated
      protein, and transaldolase 1. Compared to previous results, where cells were
      exposed to styrene, for the chlorinated aromatic substances besides oxidative
      stress, apoptosis was found as the predominant cellular response mechanism.

PMID- 21171654
TI  - The influence of the linkage pattern on the optoelectronic properties of
      polysilafluorenes: a theoretical study.
AB  - Polysilafluorenes have recently received increasing attention for a wide range of
      optoelectronic applications due to their improved performance over polyfluorenes
      and polycarbazoles. To reveal their molecular structures, optoelectronic
      properties, and structure-property relationships, a systematic study of the
      influence of the linkage pattern on the optoelectronic properties of
      polysilafluorenes was performed via quantum chemistry calculations. The optimized
      geometries, electronic properties, frontier molecular orbitals, singlet and
      triplet energies, ionization potentials, electron affinities, reorganization
      energies, and absorption and circular dichroism spectra of the model compounds
      have been calculated and analyzed. The great impacts of the linkage pattern on
      the structural, electronic, and optical properties of the silafluorene-based
      materials have been observed, and the effect mode of the linkage pattern has been
      discussed. Good coordination between the theoretical and experimental results has
      been found. The unreported poly(1,8-silafluorene)s are expected to be very
      interesting optoelectronic materials with high electronic bandgap (E(g)) and
      triplet energy ((3)E(g)), high electron injection property, high hole and
      electron transport properties, strong circular dichroism signals, and modest
      effective conjugation length, which can be used as high-performance blue or deep
      blue light emitting diodes, ambipolar host materials for blue phosphorescent
      emitters, and helically chiral conjugated materials.

PMID- 21171653
TI  - DIGE-based protein expression analysis of B[a]P-exposed hepatoma cells reveals a
      complex stress response including alterations in oxidative stress, cell cycle
      control, and cytoskeleton motility at toxic and subacute concentrations.
AB  - Although the effects of high concentrations of the carcinogen benzo[a]pyrene
      (B[a]P) have been studied extensively, little is known about its effects at
      subacute toxic concentrations, which are typical for environmental pollutants. We
      exposed murine Hepa1c1c7 cells to a toxic concentration (5 MUM) and a subacute
      concentration (50 nM) of B[a]P over a period of 2-24 h to differentiate between
      acute and pseudochronic effects and conducted a time-course analysis of B[a]P
      influenced protein expression by DIGE. In total, a set of 120 spots were found to
      be significantly altered due to B[a]P exposure of which 112 were subsequently
      identified by mass spectrometry. Clustering and principal component analysis were
      conducted to identify sets of proteins responding in a concerted manner to the
      exposure. Our results indicate an immediate response to the contaminant at the
      protein level and demonstrate that B[a]P exposure alters the cellular response by
      disturbing proteins involved in oxidative stress, cell cycle regulation,
      apoptosis, and cytoskeleton organization. Furthermore, network analysis of
      protein-protein interactions revealed a complex network of interacting, B[a]P
      regulated proteins mostly belonging to the cytoskeleton organization and several
      signal transduction pathways.

PMID- 21171657
TI  - Thermodynamics of the formaldehyde-water and formaldehyde-ice systems for
      atmospheric applications.
AB  - Formaldehyde (HCHO) is a species involved in numerous key atmospheric chemistry
      processes that can significantly impact the oxidative capacity of the atmosphere.
      Since gaseous HCHO is soluble in water, the water droplets of clouds and the ice
      crystals of snow exchange HCHO with the gas phase and the partitioning of HCHO
      between the air, water, and ice phases must be known to understand its chemistry.
      This study proposes thermodynamic formulations for the partitioning of HCHO
      between the gas phase and the ice and liquid water phases. A reanalysis of
      existing data on the vapor-liquid equilibrium has shown the inadequacy of the
      Henry's law formulation, and we instead propose the following equation to predict
      the mole fraction of HCHO in liquid water at equilibrium, X(HCHO,liq), as a
      function of the partial pressure P(HCHO) (Pa) and temperature T (K): X(HCHO,liq)
      = 1.700 * 10(-15) e((8014/T))(P(HCHO))(1.105). Given the paucity of data on the
      gas-ice equilibrium, the solubility of HCHO and the diffusion coefficient
      (D(HCHO)) in ice were measured by exposing large single ice crystals to low
      P(HCHO). Our recommended value for D(HCHO) over the temperature range 243-266 K
      is D(HCHO) = 6 * 10(-12) cm(2) s(-1). The solubility of HCHO in ice follows the
      relationship X(HCHO,ice) = 9.898 * 10(-13) e((4072/T))(P(HCHO))(0.803).
      Extrapolation of these data yields the P(HCHO) versus 1/T phase diagram for the
      H(2)O-HCHO system. The comparison of our results to existing data on the
      partitioning of HCHO between the snow and the atmosphere in the high arctic
      highlights the interplay between thermodynamic equilibrium and kinetics processes
      in natural systems.

PMID- 21171656
TI  - Observing the solubilization of lipid bilayers by detergents with optical
      microscopy of GUVs.
AB  - The solubilization of lipid bilayers by detergents was studied with optical
      microscopy of giant unilamellar vesicles (GUVs) composed of palmitoyl oleoyl
      phosphatidylcholine (POPC). A solution of the detergents Triton X-100 (TX-100)
      and sodium dodecyl sulfate (SDS) was injected with a micropipette close to single
      GUVs. The solubilization process was observed with phase contrast and
      fluorescence microscopy and found to be dependent on the detergent nature. In the
      presence of TX-100, GUVs initially showed an increase in their surface area, due
      to insertion of TX-100 with rapid equilibration between the two leaflets of the
      bilayer. Then, above a solubility threshold, several holes opened, rendering the
      bilayer a lace fabric appearance, and the bilayer gradually vanished. On the
      other hand, injection of SDS caused initially an increase in the membrane
      spontaneous curvature, which is mainly associated with incorporation of SDS in
      the outer layer only. This created a stress in the membrane, which caused either
      opening of transient macropores with substantial decrease in vesicle size or
      complete vesicle bursting. In another experimental setup, the extent of
      solubilization/destruction of a collection of GUVs was measured as a function of
      either TX-100 or SDS concentration.

PMID- 21171658
TI  - Modeling the dissociation conditions of salt hydrates and gas semiclathrate
      hydrates: application to lithium bromide, hydrogen iodide, and tetra-n
      butylammonium bromide + carbon dioxide systems.
AB  - A thermodynamic approach is proposed to determine the dissociation conditions of
      salt hydrates and semiclathrate hydrates. The thermodynamic properties of the
      liquid phase are described with the SAFT-VRE equation of state, and the solid
      liquid equilibria are solved by applying the Gibbs energy minimization criterion
      under stoichiometric constraints. The methodology is applied to water + halide
      salt systems, and an excellent description of the solid-liquid coexistence curves
      is obtained. The approach is extended to the water + tetra-n-butylammonium
      bromide (TBAB) binary mixture, and an accurate representation of the solid-liquid
      coexistence curves and dissociation enthalpies is obtained. The van der Waals
      Platteeuw (vdW-P) theory combined with the new model for salt hydrates is used to
      determine the dissociation temperatures of semiclathrate hydrates of TBAB +
      carbon dioxide. A good description of the dissociation pressures of CO(2)
      semiclathrate hydrates is obtained over wide temperature, pressure, and TBAB
      composition ranges (AAD = 10.5%). For high TBAB weight fractions the new model
      predicts a change of hydrate structure from type A to type B as the partial
      pressure of CO(2) is increased. The model can also capture a change of behavior
      with respect to TBAB concentration, which has been observed experimentally: an
      increase of the TBAB weight fraction leads to a stabilization of the gas
      semiclathrate hydrate at low initial TBAB concentrations below the stoichiometric
      composition but leads to a destabilization of the hydrate at TBAB concentrations
      above the stoichiometric composition.

PMID- 21171655
TI  - Role of cationic group structure in membrane binding and disruption by
      amphiphilic copolymers.
AB  - Cationic, amphiphilic polymers are currently being used as antimicrobial agents
      that disrupt biomembranes, although their mechanisms remain poorly understood.
      Herein, membrane association and disruption by amphiphilic polymers bearing
      primary, tertiary, or quaternary ammonium salt groups reveal the role of cationic
      group structure in the polymer-membrane interaction. The dissociation constants
      of polymers to liposomes of POPC were obtained by a fluorometric assay,
      exploiting the environmental sensitivity of dansyl moieties in the polymer end
      groups. Dye leakage from liposomes and solid-state NMR provided further insights
      into the polymer-induced membrane disruption. Interestingly, the polymers with
      primary amine groups induced reorganization of the bilayer structure to align
      lipid headgroups perpendicular to the membrane. The results showed that polymers
      bearing primary amines exceed the tertiary and quaternary ammonium counterparts
      in membrane binding and disrupting abilities. This is likely due to enhanced
      complexation of primary amines to the phosphate groups in the lipids, through a
      combination of hydrogen bonding and electrostatic interactions.

PMID- 21171659
TI  - Medium effects on the nucleation and growth mechanisms during the redox switching
      dynamics of conducting polymers: case of poly(3,4-ethylenedioxythiophene).
AB  - The redox switching dynamics of poly(3,4-ethylenedioxythiophene) (PEDOT) in an
      acetonitrile solution and a room temperature ionic liquid, 1-ethyl-3
      methylimidazolium bis(trifluoromethylsulfonyl)imide (EmiTFSI), are investigated
      by means of potential step experiments. Redox switching can be viewed as a phase
      transition in which the nucleation and growth processes occur. We have developed
      a phenomenological model allowing the determination of the kinetic parameters.
      Two limiting cases are shown as follows: (i) a progressive and (ii) an
      instantaneous nucleation. In all cases, the growth process is described in terms
      of a self-exchange electron transfer reaction. We show that the mechanisms depend
      upon the medium. In acetonitrile, progressive nucleation and growth occur during
      oxidation (p-doping), whereas nucleation is instantaneous in the reduction of the
      PEDOT film. On the other hand, instantaneous nucleation and growth mechanisms are
      observed for both oxidation and reduction in EmiTFSI. The difference in the
      mechanisms results from the ionic exchange process associated with electron
      transfer and the initial structure of the film (open or compact). The influence
      of the applied potential on the dynamics is analyzed for both media.

PMID- 21171660
TI  - Electronically excited states of vitamin B12 and methylcobalamin: theoretical
      analysis of absorption, CD, and MCD data.
AB  - Linear and quadratic response time-dependent density functional theory (TD-DFT)
      has been applied to investigate absorption (Abs), circular dichroism (CD), and
      magnetic CD (MCD) spectra of cyanocobalamin (CNCbl) and methylcobalamin (MeCbl).
      Although electronically excited states of both cobalamins have been probed by
      applying different experimental techniques, their exact nature remains poorly
      understood from an electronic structure point of view. Recent theoretical studies
      have revealed a lot of relevant information about their properties but also left
      some unresolved issues related to the nature of individual transitions. In this
      contribution, not only Abs but also CD and MCD spectra of both cobalamins were
      computed for direct comparison with experiment. The results were evaluated with
      respect to the choice of exchange-correlation functional, basis set, and the
      environment (gas phase or solvent) used in the calculation. Taking into account
      the complexity of the CNCbl and MeCbl systems, reliable agreement between theory
      and experiment was achieved based on calculations employing the BP86 functional,
      particularly for the low-energy alpha/beta bands. This spectral range has been
      traditionally interpreted as a vibrational progression associated with a single
      electronic excitation, but according to the present analysis for both cobalamins,
      these bands are best interpreted as consisting of multiple electronic
      transitions.

PMID- 21171661
TI  - Synthesis and isolation of 5,6-dihydro-4H-1,3-oxazine hydrobromides by
      autocyclization of N-(3-bromopropyl)amides.
AB  - 5,6-Dihydro-4H-1,3-oxazine hydrobromides have been synthesized by the
      nucleophilic autocyclo-O-alkylation of N-(3-bromopropyl)amides under neutral
      conditions in chloroform. It is found that electron-donating amide alpha
      substituents influence the autocyclization efficiency.

PMID- 21171662
TI  - Isotopomer analysis of production and consumption mechanisms of N2O and CH4 in an
      advanced wastewater treatment system.
AB  - Wastewater treatment processes are believed to be anthropogenic sources of
      nitrous oxide (N(2)O) and methane (CH(4)). However, few studies have examined the
      mechanisms and controlling factors in production of these greenhouse gases in
      complex bacterial systems. To elucidate production and consumption mechanisms of
      N(2)O and CH(4) in microbial consortia during wastewater treatment and to
      characterize human waste sources, we measured their concentrations and isotopomer
      ratios (elemental isotope ratios and site-specific N isotope ratios in asymmetric
      molecules of NNO) in water and gas samples collected by an advanced treatment
      system in Tokyo. Although the estimated emissions of N(2)O and CH(4) from the
      system were found to be lower than those from the typical treatment systems
      reported before, water in biological reaction tanks was supersaturated with both
      gases. The concentration of N(2)O, produced mainly by nitrifier-denitrification
      as indicated by isotopomer ratios, was highest in the oxic tank (ca. 4000%
      saturation). The dissolved CH(4) concentration was highest in in-flow water (ca.
      3000% saturation). It decreased gradually during treatment. Its carbon isotope
      ratio indicated that the decrease resulted from bacterial CH(4) oxidation and
      that microbial CH(4) production can occur in anaerobic and settling tanks.

PMID- 21171663
TI  - Current production by bacterial communities in microbial fuel cells enriched from
      wastewater sludge with different electron donors.
AB  - Electricity production by bacterial communities enriched from wastewater sludge
      with lactate, succinate, N-acetyl-D-glucosamine (NAG), acetate, formate, and
      uridine were monitored in dual-chamber microbial fuel cells (MFCs). Stable
      electricity production was observed after 300 h for communities enriched from
      lactate, acetate, and formate, while communities enriched with succinate, NAG,
      and uridine stabilized only after 700 h. The average peak current densities and
      maximum power densities generated from bacterial consortia were significantly
      higher than those generated from pure cultures of Shewanella oneidensis MR-1.
      Microbial assemblages were analyzed by DGGE, and planktonic and anode-attached
      bacterial communities varied as a function of electron donors: Firmicutes, beta
      Proteobacteria, and Bacteroidetes dominated the planktonic bacterial communities
      while anode-attached communities consisted mainly of delta-Proteobacteria, beta
      Proteobacteria, and Firmicutes. Similar bacterial populations were enriched in
      MFCs fed with lactate, NAG, and uridine and with succinate, acetate, and formate.
      Cross-feeding experiments with different fuels indicated that enriched microbial
      consortia were able to utilize a variety of fuel sources and displayed
      considerable stability, efficiency, and robustness of power generation in
      comparison to pure cultures. In addition, characterizations of cultivated
      Shewanella strains suggested that DGGE analysis likely missed active members of
      exoelectrogenic populations.

PMID- 21171664
TI  - Natural and synthetic small boron-containing molecules as potential inhibitors of
      bacterial and fungal quorum sensing.

PMID- 21171665
TI  - Conformation of poly(ethylene oxide) dissolved in ethylammonium nitrate.
AB  - Small angle neutron scattering has been used to investigate the morphology of 38
      kDa PEO dissolved in ethylammonium nitrate (EAN) in the dilute and semidilute
      concentration regions. At infinite dilution, the radius of gyration, R(g), is 8.1
      nm. This value decreases through the dilute regime according to a concentration
      (c) dependence of R(g) ~ c(-0.24), while above the overlap concentration a c(-1)
      dependence is followed. These values differ from aqueous solution behavior, which
      we attribute to EAN being a poorer solvent for PEO than water; EAN is in fact
      close to a theta solvent. The polymer structure on length scales less than 3 nm
      is unaffected by increasing polymer concentration, suggesting that the overall
      decrease in coil dimensions is a consequence of tighter packing of ~3 nm polymer
      "blobs" into a smaller volume.

PMID- 21171667
TI  - Change in hematologic indices over time in pediatric inflammatory bowel disease
      treated with azathioprine.
AB  - Azathioprine leads to changes in mean corpuscular volume (MCV) and white blood
      cell (WBC) indices reflecting efficacy or toxicity. Understanding the
      interactions between bone marrow stem cells and azathioprine could highlight
      abnormal response patterns as forerunners for hematologic malignancies. This
      study gives a statistical description of factors influencing the relationship
      between MCV and WBC in children with inflammatory bowel disease treated with
      azathioprine. We found that leukopenia preceded macrocytosis. Macrocytosis is
      therefore not a good predictor of leukopenia. Further studies will be necessary
      to determine the subgroup of patients at increased risk of malignancies based on
      bone marrow response.

PMID- 21171668
TI  - Clopidogrel resistance is associated with long-term thrombotic events in patients
      implanted with drug-eluting stents.
AB  - BACKGROUND: There are limited prospective data on clopidogrel resistance and
      clinical outcome of patients with selective coronary drug-eluting stent (DES)
      implantation. OBJECTIVE: To investigate whether clopidogrel resistance is
      associated with long-term thrombotic events in patients with selective coronary
      DES implantation. METHODS: A total of 154 patients who underwent selective
      percutaneous coronary intervention (PCI) with DES were enrolled in this study.
      Platelet aggregation was measured using light transmittance aggregometry (LTA)
      before clopidogrel administration (baseline) and 24 hours after loading with
      clopidogrel 300 mg. Clopidogrel resistance was defined as <=10% absolute
      difference between baseline aggregation and post-administration aggregation. All
      patients who received the same anti-platelet treatment were followed up for 1
      year after discharge for the incidence of a composite endpoint consisting of
      cardiovascular death, myocardial infarction (MI) and revascularization, and
      secondly for the incidence of stent thrombosis. RESULTS: The incidence of
      clopidogrel resistance is 20.28% in our study population. Patients who are
      complicated by diabetes mellitus, smoke, or have a higher body mass index (BMI)
      tend to have clopidogrel resistance. Patients in the clopidogrel-resistant group
      have significantly higher incidences of composite endpoints (21.88% vs 4.92%; p =
      0.006) and stent thrombosis (12.5% vs 1.64%; p = 0.017) than patients in the
      clopidogrel-response group during 1-year follow-up. CONCLUSIONS: Diabetes,
      smoking, and high BMI are associated with clopidogrel resistance, and clopidogrel
      resistance indicates an increased risk of long-term thrombotic events in patients
      implanted with DES.

PMID- 21171669
TI  - Safety, tolerability, and pharmacokinetics of etamicastat, a novel dopamine-beta
      hydroxylase inhibitor, in a rising multiple-dose study in young healthy subjects.
AB  - BACKGROUND: Activation of the sympathetic nervous system is an important feature
      in hypertension and congestive heart failure. A strategy for directly modulating
      sympathetic nerve function is to reduce the biosynthesis of norepinephrine
      (noradrenaline) via inhibition of dopamine-beta-hydroxylase (DbetaH). OBJECTIVE:
      To assess the safety, tolerability, and pharmacokinetics of etamicastat (BIA 5
      453), a new DbetaH inhibitor, following repeated dosing. METHODS: A double-blind,
      randomized, placebo-controlled study was conducted in healthy young male
      volunteers. Participants received once-daily doses of placebo or etamicastat 25,
      50, 100, 200, 400, or 600 mg, for 10 days. RESULTS: Etamicastat underwent N
      acetylation to its metabolite BIA 5-961. Etamicastat and BIA 5-961 maximum
      concentrations were achieved at 1-3 and 2-4 hours, respectively, after dosing.
      Elimination half-lives ranged from 18.1 to 25.7 hours for etamicastat and 6.7 to
      22.5 hours for BIA 5-961. Both etamicastat and BIA 5-961 followed linear
      pharmacokinetics. The extent of systemic exposure to etamicastat and BIA 5-961
      increased in an approximately dose-proportional manner, and steady-state plasma
      concentrations were attained up to 9 days of dosing. Etamicastat accumulated in
      plasma following repeated administration. The mean observed accumulation ratio
      was 1.3-1.9 for etamicastat and 1.3-1.6 for BIA 5-961. Approximately 40% of the
      etamicastat dose was recovered in urine in the form of parent compound and BIA 5
      961. There was a high variability in pharmacokinetic parameters, attributable to
      different N-acetyltransferase-2 (NAT2) phenotype. Urinary excretion of
      norepinephrine decreased following repeated administration of etamicastat.
      Etamicastat was generally well tolerated. There was no serious adverse event or
      clinically significant abnormality in clinical laboratory tests, vital signs, or
      ECG parameters. CONCLUSION: Etamicastat was well tolerated. Etamicastat undergoes
      N-acetylation, which is markedly influenced by NAT2 phenotype. NAT2 genotyping
      could be a step toward personalized medicine for etamicastat. TRIAL REGISTRATION:
      EudraCT No. 2007-004142-33.

PMID- 21171670
TI  - Evaluation of the pharmacokinetic interaction between lesogaberan (AZD3355) and
      esomeprazole in healthy subjects.
AB  - BACKGROUND: Transient lower esophageal sphincter relaxations (TLESRs) have been
      identified as a primary cause of reflux events in patients with gastroesophageal
      reflux disease (GERD). GABA(B) receptor agonists such as lesogaberan (AZD3355)
      have been shown to inhibit TLESRs in healthy subjects and patients with GERD,
      and, therefore, offer a novel therapeutic add-on strategy to acid suppression for
      the management of GERD. As lesogaberan is being developed as an add-on treatment
      for the management of patients with GERD who have a partial response to proton
      pump inhibitor (PPI) therapy, it is important to rule out any clinically
      important pharmacokinetic drug-drug interaction between lesogaberan and PPIs.
      OBJECTIVE: To evaluate the effect of esomeprazole on the pharmacokinetics and
      safety of lesogaberan and vice versa. STUDY DESIGN: This was an open-label,
      randomized, three-way crossover study. The study was open to healthy adult male
      and female subjects. The study subjects received treatment with, in random order,
      lesogaberan (150 mg twice daily [dose interval 12 hours]), esomeprazole (40 mg
      once daily), and a combination of both, during 7-day treatment periods. MAIN
      OUTCOME: The presence or absence of pharmacokinetic interactions between
      lesogaberan and esomeprazole was assessed by measuring the steady-state area
      under the plasma concentration-time curves during the dosing interval (AUC(tau))
      and the maximum observed plasma concentration (C(max)) for lesogaberan and
      esomeprazole. RESULTS: Thirty male subjects (mean age 23.2 years, 97% Caucasian)
      were randomized to treatment and 28 subjects completed the study (one subject was
      lost to follow-up, and one subject discontinued due to an adverse event). The 95%
      confidence intervals of the geometric mean ratios for AUC(tau) and C(max) of
      lesogaberan and esomeprazole administered alone and concomitantly were within the
      recognized boundaries of bioequivalence (0.8-1.25). No new safety concerns were
      raised during this study. The number of patients with adverse events during
      treatment with lesogaberan alone (n = 17) and concomitantly with esomeprazole (n
      = 18) were comparable but higher than with esomeprazole alone (n = 10).
      Paresthesia (episodic, mild, and transient), pharyngitis, and flatulence were the
      most frequently reported adverse events. CONCLUSIONS: There was no observed
      pharmacokinetic interaction between lesogaberan and esomeprazole when
      concomitantly administered to healthy subjects, and concomitant therapy was well
      tolerated. TRIAL REGISTRATION NUMBER (clinicaltrials.gov): NCT00684190.

PMID- 21171671
TI  - Niacin extended release (ER)/simvastatin (Simcor(r)): a guide to its use in lipid
      regulation.
AB  - Oral fixed-dose niacin extended release/simvastatin is associated with clinically
      relevant improvements in plasma lipid profiles, including lowering of non-high
      density lipoprotein cholesterol levels, relative to simvastatin monotherapy in
      patients with mixed dyslipidemias who had not responded fully to simvastatin
      monotherapy, and is generally well tolerated.

PMID- 21171672
TI  - Abiraterone acetate.
AB  - Abiraterone acetate (CB 7630; CB7630; JNJ-212082), the 3beta-acetate prodrug of
      abiraterone, is structurally related to ketoconazole and is being developed by
      Cougar Biotechnology as a hormonal therapy for advanced prostate and breast
      cancers. As a selective inhibitor of adrenal androgens, it is thought to be a
      safer product than existing second-line hormonal therapies. This review discusses
      the key development milestones and therapeutic trials of this drug.

PMID- 21171673
TI  - Tofacitinib.
AB  - Tofacitinib (CP-690,550; CP-690550; CP690550), an orally active
      immunosuppressant, is being developed by Pfizer for the treatment of rheumatoid
      arthritis, inflammatory bowel disease, dry eyes, ankylosing spondylitis,
      psoriasis, psoriatic arthritis, and for the prevention of transplant rejection.
      Tofacitinib specifically inhibits Janus activated kinase 3 (JAK3), which has a
      pivotal role in cytokine signal transduction that governs lymphocyte survival,
      proliferation, differentiation, and apoptosis. This review discusses the key
      development milestones and therapeutic trials of this drug.

PMID- 21171675
TI  - Communication: On the locality of hydrogen bond networks at hydrophobic
      interfaces.
AB  - The formation of structured hydrogen bond networks in the solvation shells
      immediate to hydrophobic solutes is crucial for a large number of water mediated
      processes. A long lasting debate in this context regards the mutual influence of
      the hydrophobic solute into the bulk water and the role of the hydrogen bond
      network of the bulk in supporting the solvation structure around a hydrophobic
      molecule. In this context we present a molecular dynamics study of the solvation
      of various hydrophobic molecules where the effect of different regions around the
      solvent can be analyzed by employing an adaptive resolution method, which can
      systematically separate local and nonlocal factors in the structure of water
      around a hydrophobic molecule. A number of hydrophobic solutes of different sizes
      and two different model potential interactions between the water and the solute
      are investigated.

PMID- 21171676
TI  - Communication: Experimental proof of symmetry breaking in tilted smectics
      composed of molecules with axial chirality.
AB  - For the first time, domains with twisted structures have been established in
      planar samples of achiral compounds in tilted smectic C phase. This evidences
      separation of molecular conformers differing in the sense of axial chirality and
      confirms polar C(2) symmetry of these domains. A simple model considering polar
      surface anchoring energy and bulk energy of the twist can account for this
      finding. Conditions for coexistence of twisted and homogeneous domains are
      discussed.

PMID- 21171677
TI  - Steepest descent reaction path integration using a first-order predictor
      corrector method.
AB  - The theoretical treatment of chemical reactions inevitably includes the
      integration of reaction pathways. After reactant, transition structure, and
      product stationary points on the potential energy surface are located, steepest
      descent reaction path following provides a means for verifying reaction
      mechanisms. Accurately integrated paths are also needed when evaluating reaction
      rates using variational transition state theory or reaction path Hamiltonian
      models. In this work an Euler-based predictor-corrector integrator is presented
      and tested using one analytic model surface and five chemical reactions. The use
      of Hessian updating, as a means for reducing the overall computational cost of
      the reaction path calculation, is also discussed.

PMID- 21171678
TI  - Phase behavior of polydisperse spheres: simulation strategies and an application
      to the freezing transition.
AB  - The statistical mechanics of phase transitions in dense systems of polydisperse
      particles presents distinctive challenges to computer simulation and analytical
      theory alike. The core difficulty, namely, dealing correctly with particle size
      fractionation between coexisting phases, is set out in the context of a critique
      of previous simulation work on such systems. Specialized Monte Carlo simulation
      techniques and moment free energy method calculations, capable of treating
      fractionation exactly, are then described and deployed to study the fluid-solid
      transition of an assembly of repulsive spherical particles described by a top-hat
      "parent" distribution of particle sizes. The cloud curve delineating the solid
      fluid coexistence region is mapped as a function of the degree of polydispersity
      delta, and the properties of the incipient "shadow" phases are presented. The
      coexistence region is found to shift to higher densities as delta increases, but
      does not exhibit the sharp narrowing predicted by many theories and some
      simulations.

PMID- 21171679
TI  - Non-Born-Oppenheimer approximation for very weakly bound states of molecular
      anions.
AB  - The influence of nuclear rotation on weak electron binding in the long range
      field of a linear polar molecule is treated in a way that leads ultimately, with
      suitable approximation, to the familiar equations for close coupling of electron
      nuclear-rotational motions. Subsequently, a conventional pseudopotential
      approximation is invoked to examine the rotational spectra of HCN and DCN anions.
      It is shown that the number of rotationally excited anion states cannot be
      reliably predicted by assuming that zero binding occurs when the rotational
      energy equals the electron affinity obtained in the Born-Oppenheimer
      approximation. A method is suggested for combining accurate molecular orbital and
      parameterized pseudopotential methods to provide accurate electron affinities for
      very weakly bound anionic states.

PMID- 21171680
TI  - Crystal structure prediction using the minima hopping method.
AB  - A structure prediction method is presented based on the minima hopping method. To
      escape local minima, moves on the configurational enthalpy surface are performed
      by variable cell shape molecular dynamics. To optimize the escape steps the
      initial atomic and cell velocities are aligned to low curvature directions of the
      current local minimum. The method is applied to both silicon crystals and well
      studied binary Lennard-Jones mixtures. For the latter new putative ground state
      structures are presented. It is shown that a high success rate is achieved and a
      reliable prediction of unknown ground state structures is possible.

PMID- 21171681
TI  - Scalable free energy calculation of proteins via multiscale essential sampling.
AB  - A multiscale simulation method, "multiscale essential sampling (MSES)," is
      proposed for calculating free energy surface of proteins in a sizable dimensional
      space with good scalability. In MSES, the configurational sampling of a full
      dimensional model is enhanced by coupling with the accelerated dynamics of the
      essential degrees of freedom. Applying the Hamiltonian exchange method to MSES
      can remove the biasing potential from the coupling term, deriving the free energy
      surface of the essential degrees of freedom. The form of the coupling term
      ensures good scalability in the Hamiltonian exchange. As a test application, the
      free energy surface of the folding process of a miniprotein, chignolin, was
      calculated in the continuum solvent model. Results agreed with the free energy
      surface derived from the multicanonical simulation. Significantly improved
      scalability with the MSES method was clearly shown in the free energy calculation
      of chignolin in explicit solvent, which was achieved without increasing the
      number of replicas in the Hamiltonian exchange.

PMID- 21171682
TI  - A linked electron pair functional.
AB  - A modification of the variational configuration interaction functional in the
      first-order interacting space for molecular electronic structure is presented.
      The modified functional is a fully linked expression that by construction is
      extensive and invariant to transformations of the underlying orbital basis and is
      exact for an ensemble of separated two-electron subsystems. In addition, an
      approximation to variational coupled cluster is generated through truncation of
      the exponential cluster operator. When combined, these methods demonstrate
      accuracy that exceeds that of the standard coupled-cluster method, in particular
      in situations where the reference Slater determinant is not a good approximation.

PMID- 21171683
TI  - Equation of state and liquid-vapor equilibrium of polarizable Stockmayer fluids.
AB  - In this work we develop the concept of an effective potential to obtain the
      equation of state of polarizable Stockmayer (PSM) fluids. This potential consists
      of a Lennard-Jones function with appropriate energy and distance parameters that
      depend on the reduced dipolar moment MU(*) and polarizability alpha(*). The
      approach deals accurately with polarizable SM fluids with MU(*)<=2.0 and
      alpha(*)<=0.1. However, prediction of second virial coefficients is reliable up
      to MU(*)<=4.0. When the low-density sphericalized potential is used at moderate
      and large densities, the effect of the dipole-dipole attraction is overestimated
      in agreement with an effect previously found in the literature. This effect can
      be traced back to a frustration mechanism due to the interaction between three
      and more dipoles. We propose a model to account for this frustration effect and
      are able to reproduce the vapor-liquid equilibrium of polarizable SM fluids in
      agreement with simulated results from the literature. Molecular dynamics
      simulations were carried out to show that the effective SM fluid has a radial
      distribution function very close to that of the true SM system.

PMID- 21171684
TI  - Structures of tin cluster cations Sn3(+) to Sn15(+).
AB  - We employ a combination of ion mobility measurements and an unbiased systematic
      structure search with density functional theory methods to study structure and
      energetics of gas phase tin cluster cations, Sn(n)(+), in the range of n = 3-15.
      For Sn(13)(+) we also carry out trapped ion electron diffraction measurements to
      ascertain the results obtained by the other procedures. The structures for the
      smaller systems are most easily described by idealized point group symmetries,
      although they are all Jahn-Teller distorted: D(3h) (trigonal bipyramid), D(4h)
      (octahedron), D(5h) (pentagonal bipyramid) for n = 5, 6, and 7. For the larger
      systems we find capped D(5h) for Sn(8)(+) and Sn(9)(+), D(3h) (tricapped trigonal
      prism) and D(4d) (bicapped squared antiprism) plus adatoms for n = 10, 11, 14,
      and 15. A centered icosahedron with a peripheral atom removed is the dominant
      motif in Sn(12)(+). For Sn(13)(+) the calculations predict a family of virtually
      isoenergetic isomers, an icosahedron and slightly distorted icosahedra, which are
      about 0.25 eV below two C(1) structures. The experiments indicate the presence of
      two structures, one from the I(h) family and a prolate C(1) isomer based on fused
      deltahedral moieties.

PMID- 21171685
TI  - Numerical simulation of free evolution in solid-state nuclear magnetic resonance
      using low-order correlations in Liouville space.
AB  - The design of simulations of free evolution in dipolar-coupled nuclear-spin
      systems using low-order correlations in Liouville space (LCL) is discussed, and a
      computational scheme relying on the Suzuki-Trotter algorithm and involving
      minimal memory requirements is described. The unusual nature of the approximation
      introduced by Liouville-space reduction in a spinning solid is highlighted by
      considering the accuracy of LCL simulations at different spinning frequencies,
      the quasiequilibria achieved by spin systems in LCL simulations, and the growth
      of high-order coherences in the exact dynamics. In particular, it is shown that
      accurate LCL simulations of proton spin diffusion occur in a regime where the
      reduced space excludes the coherences that make the dominant contribution to
      ?sigma?(2), the norm-squared of the density matrix.

PMID- 21171686
TI  - Chiral symmetry breaking in a microscopic model with asymmetric autocatalysis and
      inhibition.
AB  - Asymmetric autocatalysis and inhibition have been proposed as key processes in
      the spontaneous emergence of chiral symmetry breaking in a prebiotic world. An
      elementary lattice model is formulated to simulate the kinetics of chiral
      symmetry breaking via autocatalysis and inhibition in a mixture of prochiral
      reactants, chiral products, and inert solvent. Starting from a chirally unbiased
      initial state, spontaneous symmetry breaking occurs in spite of equal a priori
      probability for creating either product enantiomer, and the coupled reaction
      diffusion processes subsequently amplify the random early-stage symmetry
      breaking. The processes of reaction and diffusion are kinetically intertwined in
      a way leading to competition in the appearance of enantiomeric excess. An
      effective transition temperature can be identified below which spontaneous
      symmetry breaking appears. In the absence of inhibition, reactions are
      predominantly autocatalytic under both reaction control (fast diffusion, slow
      reaction) or diffusion control (fast reaction, slow diffusion) conditions. In the
      presence of inhibition, simulations with different system sizes converge to the
      same transition temperature under reaction control conditions, and in this limit
      the reactions are predominantly nonautocatalytic.

PMID- 21171687
TI  - Understanding mixing of Ni and Pt in the Ni/Pt(111) bimetallic catalyst via
      molecular simulation and experiments.
AB  - Molecular dynamics (MD) simulations employing embedded atom method potentials and
      ultrahigh vacuum (UHV) experiments were carried out to study the mixing process
      between the Ni and Pt atoms in the Ni/Pt(111) bimetallic system. The barrier for
      a Ni atom to diffuse from the top surface to the subsurface layer is rather high
      (around 1.7 eV) as calculated using the nudged elastic band (NEB) method.
      Analysis of the relaxation dynamics of the Ni atoms showed that they undergo
      diffusive motion through a mechanism of correlated hops. At 600 K, all Ni atoms
      remain trapped on the top surface due to large diffusion barriers. At 900 K, the
      majority of Ni atoms diffuse to the second layer and at 1200 K diffusion to the
      bulk is observed. We also find that smaller Ni coverages and the presence of Pt
      steps facilitate the Ni-Pt mixing. By simulated annealing simulations, we found
      that in the mixed state, the Ni fraction oscillates between layers, with the
      second layer being Ni-richer at equilibrium. The simulation results at multiple
      time scales are consistent with the experimental data.

PMID- 21171688
TI  - Ordered equilibrium structures of soft particles in thin layers.
AB  - Considering a system of gaussian particles confined between two hard, parallel
      plates, we investigate at T = 0, ordered equilibrium configurations that the
      system forms as the distance D between the plates gradually increases. Using a
      very sensitive and reliable optimization technique that is based on ideas of
      genetic algorithms, we are able to identify the emerging sequences of the
      energetically most favorable structures. Although the resulting phase diagram is
      rather complex, its essential features can be reduced to the discussion of two
      archetypes of structural transitions: (i) a continuous transformation at a fixed
      number of layers, leading from a square to a centered rectangular and then to a
      hexagonal lattice; (ii) a discontinuous transition, transforming a hexagonal to a
      square lattice via complex intermediate structures, i.e., the so-called buckling
      transition, which is encountered as the system forms a new layer. Detailed Monte
      Carlo simulations are able to confirm the theoretical predictions on a
      semiquantitative level but are not able to grasp the tiny energetic differences
      between competing structures.

PMID- 21171689
TI  - The van Hove distribution function for brownian hard spheres: dynamical test
      particle theory and computer simulations for bulk dynamics.
AB  - We describe a test particle approach based on dynamical density functional theory
      (DDFT) for studying the correlated time evolution of the particles that
      constitute a fluid. Our theory provides a means of calculating the van Hove
      distribution function by treating its self and distinct parts as the two
      components of a binary fluid mixture, with the "self " component having only one
      particle, the "distinct" component consisting of all the other particles, and
      using DDFT to calculate the time evolution of the density profiles for the two
      components. We apply this approach to a bulk fluid of Brownian hard spheres and
      compare to results for the van Hove function and the intermediate scattering
      function from Brownian dynamics computer simulations. We find good agreement at
      low and intermediate densities using the very simple Ramakrishnan-Yussouff [Phys.
      Rev. B 19, 2775 (1979)] approximation for the excess free energy functional.
      Since the DDFT is based on the equilibrium Helmholtz free energy functional, we
      can probe a free energy landscape that underlies the dynamics. Within the mean
      field approximation we find that as the particle density increases, this
      landscape develops a minimum, while an exact treatment of a model confined
      situation shows that for an ergodic fluid this landscape should be monotonic. We
      discuss possible implications for slow, glassy, and arrested dynamics at high
      densities.

PMID- 21171690
TI  - Low O2 dissociation barrier on Pt(111) due to adsorbate-adsorbate interactions.
AB  - O(2) dissociation on Pt(111) has been followed at low and saturation coverage
      using temperature-programmed x-ray photoelectron spectroscopy and simulated with
      mean-field kinetic modeling, yielding dissociation (E(a)) and desorption (E(d))
      barriers of 0.32 and 0.36 eV, respectively. Density functional theory
      calculations show that E(a) is strongly influenced by the O-O interatomic
      potential in the atomic final state: of the supercells considered, that which
      maximizes attractive third-nearest-neighbor interactions in the atomic final
      state yields both the lowest computed dissociation barrier (0.24 eV) and the best
      agreement with experiment. It is proposed that the effect of adsorbate-adsorbate
      interactions must be considered when modeling catalytic processes involving
      dissociative steps.

PMID- 21171691
TI  - Adsorption configuration effects on the surface diffusion of large organic
      molecules: the case of Violet Lander.
AB  - Violet Lander (C(108)H(104)) is a large organic molecule that when deposited on
      Cu(110) surface exhibits lock-and-key like behavior [Otero et al., Nature Mater.
      3, 779 (2004)]. In this work, we report a detailed fully atomistic molecular
      mechanics and molecular dynamics study of this phenomenon. Our results show that
      it has its physical basis on the interplay of the molecular hydrogens and the
      Cu(110) atomic spacing, which is a direct consequence of the matching between
      molecule and surface dimensions. This information could be used to find new
      molecules capable of displaying lock-and-key behavior with new potential
      applications in nanotechnology.

PMID- 21171692
TI  - Structure and adsorption of water in nonuniform cylindrical nanopores.
AB  - Grand canonical Monte Carlo simulations are used to examine the adsorption and
      structure of water in the interior of cylindrical nanopores in which the axial
      symmetry is broken either by varying the radius as a function of position along
      the pore axis or by introducing regions where the characteristic strength of the
      water-nanopore interaction is reduced. Using the extended simple point charge
      (SPC/E) model for water, nanopores with a uniform radius of 6.0 A are found to
      fill with water at chemical potentials approximately 0.5 kJ/mol higher than the
      chemical potential of the saturated vapor. The water in these filled pores exists
      in either a weakly structured fluidlike state or a highly structured uniformly
      polarized state composed of a series of stacked water clusters with pentagonal
      cross sections. This highly structured state can be disrupted by creating
      hydrophobic regions on the surface of the nanopore, and the degree of disruption
      can be systematically controlled by adjusting the size of the hydrophobic
      regions. In particular, hydrophobic banded regions with lengths larger than 9.2 A
      result in a complete loss of structure and the formation of a liquid-vapor
      coexistence in the tube interior. Similarly, the introduction of spatial
      variation in the nanopore radius can produce two condensation transitions at
      distinct points along the filling isotherm.

PMID- 21171693
TI  - Adsorption geometry, molecular interaction, and charge transfer of triphenylamine
      based dye on rutile TiO2(110).
AB  - The fast development of new organic sensitizers leads to the need for a better
      understanding of the complexity and significance of their adsorption processes on
      TiO(2) surfaces. We have investigated a prototype of the triphenylamine
      cyanoacrylic acid (donor-acceptor) on rutile TiO(2) (110) surface with special
      attention on the monolayer region. This molecule belongs to the type of dye, some
      of which so far has delivered the record efficiency of 10%-10.3% for pure organic
      sensitizers [W. Zeng, Y. Cao, Y. Bai, Y. Wang, Y. Shi, M. Zhang, F. Wang, C. Pan,
      and P. Wang, Chem. Mater. 22, 1915 (2010)]. The molecular configuration of this
      dye on the TiO(2) surface was found to vary with coverage and adopt gradually an
      upright geometry, as determined from near edge x-ray absorption fine structure
      spectroscopy. Due to the molecular interaction within the increasingly dense
      packed layer, the molecular electronic structure changes systematically: all
      energy levels shift to higher binding energies, as shown by photoelectron
      spectroscopy. Furthermore, the investigation of charge delocalization within the
      molecule was carried out by means of resonant photoelectron spectroscopy. A fast
      delocalization (~1.8 fs) occurs at the donor part while a competing process
      between delocalization and localization takes place at the acceptor part. This
      depicts the "push-pull" concept in donor-acceptor molecular system in time scale.

PMID- 21171694
TI  - Energy-gap opening and quenching in graphene under periodic external potentials.
AB  - We investigated the effects of periodic external potentials on properties of
      charge carriers in graphene using both the first-principles method based on
      density functional theory (DFT) and a theoretical approach based on a generalized
      effective spinor Hamiltonian. DFT calculations were done in a modified Kohn-Sham
      procedure that includes the effects of the periodic external potential.
      Unexpected energy band gap opening and quenching were predicted for the graphene
      superlattice with two symmetrical sublattices and those with two unsymmetrical
      sublattices, respectively. Theoretical analysis based on the spinor Hamiltonian
      showed that the correlations between pseudospins of Dirac fermions in graphene
      and the applied external potential, and the potential-induced intervalley
      scattering, play important roles in energy-gap opening and quenching.

PMID- 21171695
TI  - A comparative study of argon ion irradiated pristine and fluorinated single-wall
      carbon nanotubes.
AB  - Effect of Ar(+) ion irradiation on the structure of pristine and fluorinated
      single-wall carbon nanotubes (SWCNTs) was examined using transmission electron
      microscopy (TEM), Raman, and x-ray photoelectron spectroscopy (XPS). The TEM
      analysis revealed retention of tubular structures in both irradiated samples
      while Raman spectroscopy and XPS data indicated a partial destruction of
      nanotubes and formation of oxygen-containing groups on the nanotube surface. From
      similarity of electronic states of carbon in the irradiated pristine and
      fluorinated SWCNTs observed by XPS, it was suggested that defluorination of
      nanotubes proceeded with breaking of C-F bonds.

PMID- 21171696
TI  - Structural and dynamical analysis of monodisperse and polydisperse colloidal
      systems.
AB  - We present a semigrand ensemble Monte Carlo and Brownian dynamics simulation
      study of structural and dynamical properties of polydisperse soft spheres
      interacting via purely repulsive power-law potentials with a varying degree of
      "softness." Comparisons focus on crystal and amorphous phases at their
      coexistence points. It is shown through detailed structural analysis that as
      potential interactions soften, the "quality of crystallinity" of both
      monodisperse and polydisperse systems deteriorates. In general, polydisperse
      crystalline phases are characterized by a more ordered structure than the
      corresponding monodisperse ones (i.e., for the same potential softness). This
      counter-intuitive feature originates partly from the fact that particles of
      different sizes may be accommodated more flexibly in a crystal structure and from
      the reality that coexistence (osmotic) pressure is substantially higher for
      polydisperse systems. These trends diminish for softer potentials. Potential
      softness eventually produces substitutionally disordered crystals. However,
      substitutional order is apparent for the hard-spherelike interactions.
      Diffusionwise, crystals appear quite robust with a slight difference in the
      vibrational amplitudes of small and large particles. This difference, again,
      diminishes with potential softness. Overcrowding in amorphous polydisperse
      suspensions causes "delayed" diffusion at intermediate times.

PMID- 21171697
TI  - Slow dynamics of a colloidal lamellar phase.
AB  - We used x-ray photon correlation spectroscopy to study the dynamics in the
      lamellar phase of a platelet suspension as a function of the particle
      concentration. We measured the collective diffusion coefficient along the
      director of the phase, over length scales down to the interparticle distance, and
      quantified the hydrodynamic interaction between the particles. This interaction
      sets in with increasing concentration and can be described qualitatively by a
      simplified model. No change in the microscopic structure or dynamics is observed
      at the transition between the fluid and the gel-like lamellar phases.

PMID- 21171698
TI  - Atomistic theory of amyloid fibril nucleation.
AB  - We consider the nucleation of amyloid fibrils at the molecular level when the
      process takes place by a direct polymerization of peptides or protein segments
      into beta-sheets. Employing the atomistic nucleation theory (ANT), we derive a
      general expression for the work to form a nanosized amyloid fibril
      (protofilament) composed of successively layered beta-sheets. The application of
      this expression to a recently studied peptide system allows us to determine the
      size of the fibril nucleus, the fibril nucleation work, and the fibril nucleation
      rate as functions of the supersaturation of the protein solution. Our analysis
      illustrates the unique feature of ANT that the size of the fibril nucleus is a
      constant integer in a given supersaturation range. We obtain the ANT nucleation
      rate and compare it with the rates determined previously in the scope of the
      classical nucleation theory (CNT) and the corrected classical nucleation theory
      (CCNT). We find that while the CNT nucleation rate is orders of magnitude greater
      than the ANT one, the CCNT and ANT nucleation rates are in very good quantitative
      agreement. The results obtained are applicable to homogeneous nucleation, which
      occurs when the protein solution is sufficiently pure and/or strongly
      supersaturated.

PMID- 21171702
TI  - In focus: biointerphase science in Singapore.

PMID- 21171703
TI  - Cooperative photoinduced two-dimensional condensation in Langmuir films observed
      using nanosecond pump-probe Brewster angle microscopy.
AB  - Two-dimensional condensation was initiated in a self-assembled mixed monolayer of
      spiropyran and octadecanol by a nanosecond laser pulse. The dynamics of the
      process were monitored using nanosecond pump-probe Brewster angle microscopy.
      Domain growth followed a power law with a growth exponent of 0.47 at a velocity
      approaching 20 ms(-1). This represents a limit for the rate of longitudinal
      signaling of pressure waves through a self-assembled amphiphilic layer at an
      interface and adds to our understanding of signal transmission rates in
      biomimetic membranes where morphological change in one region can be signaled to
      a more remote region.

PMID- 21171704
TI  - Silica-coated quantum dots and magnetic nanoparticles for bioimaging applications
      (Mini-Review).
AB  - Fluorescent quantum dots (e.g., CdSe-ZnS) and magnetic nanoparticles (e.g.,
      Fe(2)O(3) or Fe(3)O(4)) are two important candidate systems that have been
      emerging as potential probes for bioimaging applications. This review focuses on
      the development of silica-coated inorganic probes (optical and magnetic) that are
      originated mainly from the author's laboratory for bioimaging applications. The
      recent developments in the synthesis of rare earth nanoparticles for
      multimodality imaging are also delineated.

PMID- 21171705
TI  - Current development of bioreactors for extracorporeal bioartificial liver
      (Review).
AB  - The research and development of extracorporeal bioartificial liver is gaining
      pace in recent years with the introduction of a myriad of optimally designed
      bioreactors with the ability to maintain long-term viability and liver-specific
      functions of hepatocytes. The design considerations for bioartificial liver are
      not trivial; it needs to consider factors such as the types of cell to be
      cultured in the bioreactor, the bioreactor configuration, the magnitude of fluid
      induced shear stress, nutrients' supply, and wastes' removal, and other relevant
      issues before the bioreactor is ready for testing. This review discusses the
      exciting development of bioartificial liver devices, particularly the various
      types of cell used in current reactor designs, the state-of-the-art culturing and
      cryopreservation techniques, and the comparison among many today's bioreactor
      configurations. This review will also discuss in depth the importance of
      maintaining optimal mass transfer of nutrients and oxygen partial pressure in the
      bioreactor system. Finally, this review will discuss the commercially available
      bioreactors that are currently undergoing preclinical and clinical trials.

PMID- 21171706
TI  - Impact of vitronectin concentration and surface properties on the stable
      propagation of human embryonic stem cells.
AB  - The standard method for culturing human embryonic stem cells (hESC) uses
      supporting feeder layers of cells or an undefined substrate, Matrigel(TM), which
      is a basement membrane extracted from murine sarcoma. For stem cell therapeutic
      applications, a superior alternative would be a defined, artificial surface that
      is based on immobilized human plasma vitronectin (VN), which is an adhesion
      mediating protein. Therefore, VN adsorbed to diverse polymer surfaces was
      explored for the continuous propagation of hESC. Cells propagated on VN-coated
      tissue culture polystyrene (TCPS) are karyotypically normal after >10 passages of
      continuous culture, and are able to differentiate into embryoid bodies containing
      all three germ layers. Expansion rates and pluripotent marker expression verified
      that a minimal VN surface density threshold is required on TCPS. Further
      exploration of adsorbed VN was conducted on polymer substrates with different
      properties, ranging from hydrophilic to hydrophobic and including cationic and
      anionic polyelectrolyte coatings. Despite differing surface properties, these
      substrates adsorbed VN above the required surface density threshold and were
      capable of supporting hESC expansion for >10 passages. Correlating wettability of
      the VN-coated surfaces with the response of cultured hESC, higher cell expansion
      rates and OCT-4 expression levels were found for VN-coated TCPS, which exhibits a
      water contact angle close to 65 degrees . Importantly, this simple, defined
      surface matches the performance of the benchmark Matrigel, which is a hydrogel
      with highly complex composition.

PMID- 21171707
TI  - The National University of Singapore and what it does.

PMID- 21171708
TI  - Macromolecular depletion modulates the binding of red blood cells to activated
      endothelial cells.
AB  - Adhesion of red blood cells (RBCs) to endothelial cells (ECs) is usually
      insignificant but an enhanced adhesion has been observed in various diseases
      associated with vascular complications. This abnormal adhesion under pathological
      conditions such as sickle cell disease has been correlated with increased levels
      of various plasma proteins but the detailed underlying mechanism(s) remains
      unclear. Usually it is assumed that the proadhesive effects of plasma proteins
      originate from ligand interactions cross-linking receptors on adjacent cells, but
      explicit results detailing binding sites or receptors for some proteins (e.g.,
      fibrinogen) on either RBC or EC surfaces that would support this model are
      missing. In this study, the authors tested whether there is an alternative
      mechanism. Their results demonstrate that dextran 2 MDa promotes the adhesion of
      normal RBCs to thrombin-activated ECs and that this effect becomes more
      pronounced with increasing thrombin concentration or with prolonged thrombin
      incubation time. It is concluded that depletion interaction originating from
      nonadsorbing macromolecules (i.e., dextran) can modulate the adhesion of red
      blood cells to thrombin-activated EC. This study thereby suggests macromolecular
      depletion as an alternative mechanism for the adhesion-promoting effects of
      nonadsorbing plasma proteins. These findings should not only aid in getting a
      better understanding of diseases associated with vascular complications but
      should also have many potential applications in biomedical or biotechnological
      areas that require the control of cell-cell or cell surface interactions.

PMID- 21171709
TI  - Microarray-based enzyme profiling: Recent advances and applications (Review).
AB  - Enzymes are an integral part of biological systems. They constitute a significant
      majority of all proteins expressed (an estimated 18%-29%) within eukaryotic
      genomes. It thus comes as no major surprise that enzymes have been implicated in
      many diseases and form the second largest group of drug targets, after receptors.
      Despite their involvement in a multitude of physiological processes, only a
      limited number of enzymes have thus far been well-characterized. Consequently,
      little is understood about the physiological roles, substrate specificity, and
      downstream targets of the vast majority of these important proteins. In order to
      facilitate the biological characterization of enzymes, as well as their adoption
      as drug targets, there is a need for global "-omics" solutions that bridge the
      gap in understanding these proteins and their interactions. Herein the authors
      showcase how microarray methods can be adopted to facilitate investigations into
      enzymes and their properties, in a high-throughput manner. They will focus on
      several major classes of enzymes, including kinases, phosphatases, and proteases.
      As a result of research efforts over the last decade, these groups of enzymes
      have become readily amenable to microarray-based profiling methods. The authors
      will also describe the specific design considerations that are required to
      develop the appropriate chemical tools and libraries to characterize each enzyme
      class. These include peptide substrates, activity-based probes, and chemical
      compound libraries, which may be rapidly assembled using efficient combinatorial
      synthesis or "click chemistry" strategies. Taken together, microarrays offer a
      powerful means to study, profile, and also discover potent small molecules with
      which to modulate enzyme activity.

PMID- 21171710
TI  - Advancing innovation through R&D the A*STAR way.

PMID- 21171711
TI  - Surface modification of poly(L-lactic acid) with biomolecules to promote
      endothelialization.
AB  - Rapid endothelialization is important for biodegradable blood-contacting devices
      not only to prevent thrombosis but also to prevent degradation debris from
      entering the bloodstream and causing further complications. Here the authors
      report a three-step surface modification method, by which biomolecules, such as
      gelatin and chitosan, are covalently immobilized on the surface of plasma-treated
      poly(L-lactic acid) (PLLA) via -COOH groups introduced by acrylic acid grafting
      polymerization. Surface characterization techniques, including x-ray
      photoelectron spectroscopy, contact angle measurement, and colorimetric methods
      for surface density of functional groups, proved the feasibility and stability of
      this surface modification method. Surface wettability was increased by
      biomolecules immobilization. The -COOH surface density was measured to be 4.17+/
      0.15 MUmol/cm(2), the and amount of gelatin immobilized was 4.8 MUg/cm(2). Human
      umbilical vein endothelial cell was used during in vitro study at seeding density
      of 10(4) cells/cm(2). PLLA-gAA-gelatin surface was found to enhance cell
      adhesion, spreading, focal adhesion formation, and proliferation significantly.
      Chitosan-modified PLLA shows marginally improvement in cell adhesion and
      proliferation. Endothelialization was achieved within 7 days on both modified
      PLLA surfaces. In conclusion, this work demonstrates the feasibility of the
      surface modification method, and its ability to promote complete
      endothelialization for cardiovascular applications.

PMID- 21171712
TI  - cBSA-147 for the preparation of bacterial biofilms in a microchannel reactor.
AB  - Whole cells are attractive biocatalysts, particularly if the reaction requires
      cofactors or involves multiple transformations. Immobilization of the catalyst is
      often a prerequisite for continuous processes. The highly cationic chemically
      modified plasma protein bovine serum albumin (cBSA-147) has been applied for the
      electrostatically mediated immobilization of the planktonic bacterium E. coli
      BL21 star (DE3), and the resulting biofilms were superior to those formed on poly
      L-lysine coated surfaces. The biocatalyst was immobilized in a capillary column
      (inside diameter of 530 MUm and L=30 m) and evaluated in the enantioselective
      reduction of ethyl acetoacetate to R-(-)ethyl hydroxybutyrate. In continuous
      operation in the microreactor format, the productivity of the cells was about 30%
      higher than that determined in a bench-scale fermentation system. This increase
      is attributed to the improved mass transfer over short geometrical dimensions.
      The similarity in the results indicates that studies on a biofilm-coated
      microreactor can be used for the accelerated collection of data for process
      optimization.

PMID- 21171713
TI  - Iron-based ferritin nanocore as a contrast agent.
AB  - Self-assembling protein cages have been exploited as templates for nanoparticle
      synthesis. The ferritin molecule, a protein cage present in most living systems,
      stores excess soluble ferrous iron in the form of an insoluble ferric complex
      within its cavity. Magnetic nanocores formed by loading excess iron within an
      engineered ferritin from Archaeoglobus fulgidus (AfFtn-AA) were studied as a
      potential magnetic resonance (MR) imaging contrast agent. The self-assembly
      characteristics of the AfFtn-AA were investigated using dynamic light scattering
      technique and size exclusion chromatography. Homogeneous size distribution of the
      assembled nanoparticles was observed using transmission electron microscopy. The
      magnetic properties of iron-loaded AfFtn-AA were studied using vibrating sample
      magnetometry. Images obtained from a 3.0 T whole-body MRI scanner showed
      significant brightening of T(1) images and signal loss of T(2) images with
      increased concentrations of iron-loaded AfFtn-AA. The analysis of the MR image
      intensities showed extremely high R(2) values (5300 mM(-1) s(-1)) for the iron
      loaded AfFtn-AA confirming its potential as a T(2) contrast agent.

PMID- 21171714
TI  - Adhesion, proliferation, and gene expression profile of human umbilical vein
      endothelial cells cultured on bilayered polyelectrolyte coatings composed of
      glycosaminoglycans.
AB  - This study characterized human umbilical vein endothelial cell (HUVEC) adhesion,
      proliferation, and gene expression on bilayered polyelectrolyte coatings composed
      of an outermost layer of glycosaminoglycans (hyaluronan, heparin, or chondroitin
      sulfate), with an underlying layer of poly-L-lysine or chitosan. The proportion
      of cells that adhered to the various polyelectrolyte coatings after 1 and 2 h
      incubations was quantified by the WST-8 assay. Interchanging poly-L-lysine with
      chitosan resulted in significant differences in cellular adhesion to the
      outermost glycosaminoglycan layer after 1 h, but these differences became
      insignificant after 2 h. The proliferation of HUVEC on the various bilayered
      polyelectrolyte coatings over 10 days was characterized using the WST-8 assay.
      Regardless of whether the underlying layer was poly-L-lysine or chitosan, HUVEC
      proliferation on the hyaluronan outermost layer was significantly less than on
      heparin or chondroitin sulfate. Additionally, it was observed that there was more
      proliferation with poly-L-lysine as the underlying layer, compared to chitosan.
      Subsequently, real-time polymerase chain reaction was used to analyze the
      expression of seven genes related to adhesion, migration, and endothelial
      function (VWF, VEGFR, VEGFA, endoglin, integrin-alpha5, ICAM1, and ICAM2) by
      HUVEC cultured on the various bilayered polyelectrolyte coatings for 3 days. With
      poly-L-lysine as the underlying layer, biologically significant differences
      (greater than twofold) in the expression of VWF, VEGFR, VEGFA, endoglin, and
      ICAM1 were observed among the three glycosaminoglycans. With chitosan as the
      underlying layer, all three glycosaminoglycans displayed biologically significant
      differences in the expression of VWF and VEGFR compared to the chitosan control.
      CT-HA displayed the highest level of expression of VWF, whereas expression levels
      of VEGFR were almost similar among the three glycosaminoglycans.

PMID- 21171715
TI  - Bio-inspired track-walking molecular motors (Perspective).
AB  - The emerging field of artificial track-walking molecular motors is reviewed. The
      author attempted to clarify the scientific and technological challenges that face
      the field. A comprehensive mechanistic diagram for molecular walkers was
      introduced, thereby the directions and possible routes for future development
      were suggested.

PMID- 21171716
TI  - Sustained release of complexed DNA from films: Study of bioactivity and
      intracellular tracking.
AB  - Sustained DNA delivery from polymeric films provides a means for localized and
      prolonged gene therapy. However, in the case of bioactive molecules such as
      plasmid DNA (pDNA), there are limitations on the achievable release profiles as
      well as on the maintenance of bioactivity over time. In this report, the authors
      have investigated the bioactivity of the released DNA (naked and complexed with
      lipofectamine) from polymeric films using in vitro cell transfection of COS-7
      cell lines. The polymeric system consists of a biodegradable semicrystalline
      polymer such as poly(epsilon-caprolactone) (PCL) with or without blended gelatin.
      Sustained release of lipoplexes and of pDNA is shown over several days. However,
      lipoplexes released from pure PCL films show no transfection on day 18, whereas
      lipoplexes released from PCL-gelatin films continue to transfect cells on day 18
      of release. Confocal studies were used to determine the reasons for this
      difference in transfection efficiency, and it is proposed that association of the
      lipoplex with gelatin confers protection from degradation in the cytoplasm. The
      results also showed that the bioactivity of released lipoplexes was superior to
      that of the naked pDNA. For both naked pDNA and the lipoplexes, the presence of
      gelatin helped to maintain the bioactivity over several days.

PMID- 21171717
TI  - Cationized albumin-biocoatings for the immobilization of lipid vesicles.
AB  - Tethered lipid membranes or immobilized lipid vesicles are frequently used as
      biomimetic systems. In this article, the authors presented a suitable method for
      efficient immobilization of lipid vesicles onto a broad range of surfaces,
      enabling analysis by quantitative methods even under rigid, mechanical conditions
      bare surfaces such as hydrophilic glass surfaces as well as hydrophobic polymer
      slides or metal surfaces such as gold. The immobilization of vesicles was based
      on the electrostatic interaction of zwitterionic or negatively charged lipid
      vesicles with two types of cationic chemically modified bovine serum albumin
      (cBSA) blood plasma proteins (cBSA-113 and cBSA-147). Quantitative analysis of
      protein adsorption was performed as the cBSA coatings were characterized by
      atomic force microscopy, surface zeta potential measurement, fluorescence
      microscopy, and surface plasmon spectroscopy, revealing a maximal surface
      coverage 270-280 ng/cm(2) for 0.02 mg/ml cBSA on gold. Small unilamellar vesicles
      as well as giant unilamellar vesicles (GUVs) were readily immobilized (~15 min)
      on cBSA coated surfaces. GUVs with 5-10 mol% negatively charged 1,2,-dipalmitoyl
      sn-glycero-3-phosphoglycerol remained stable in liquid for at least 5 weeks.

PMID- 21171718
TI  - Comparative cytotoxicity evaluation of lanthanide nanomaterials on mouse and
      human cell lines with metabolic and DNA-quantification assays.
AB  - Lanthanide nanomaterials are considered a less toxic alternative to quantum dots
      for bioimaging applications. This study evaluated the cytotoxicity of terbium
      (Tb)-doped gadolinium oxide (Gd(2)O(3)) and dysprosium oxide (Dy(2)O(3))
      nanoparticles exposed to human (BEAS-2B) and mouse (L929) cell lines at a
      concentration range of 200-2000 MUg/ml for 48 h. Two assay methods were utilized
      WST-8 assay (colorimetric) based on mitochondrial metabolic activity and Pico
      Green assay (fluorescence), which measures total DNA content. The authors' data
      showed that Tb-doped Gd(2)O(3) nanoparticles were consistently more toxic than Tb
      doped Dy(2)O(3) nanoparticles. However, exposure to these nanomaterials caused a
      decrease in proliferation rate for both cell lines rather than a net loss of
      viable cells after 48 h of exposure. Additionally, there was some degree of
      discrepancy observed with the two assay methods. For the mouse L929 cell line,
      the WST-8 assay yielded consistently lower proliferation rates compared to the
      Pico-Green assay, whereas the opposite trend was observed for the human BEAS-2B
      cell line. This could arise because of the differential effects of these
      nanoparticles on the metabolism of L929 and BEAS-2B cells, which in turn may
      translate to differences in their postexposure proliferation rates. Hence, the
      Pico-Green assay could have an advantage over the WST-8 assay because it is not
      skewed by the differential effects of nanomaterials on cellular metabolism.

PMID- 21171719
TI  - Singapore and the Nanyang Technological University--A young country with a young
      university on the move.

PMID- 21171720
TI  - Study of nucleic acid-gold nanorod interactions and detecting nucleic acid
      hybridization using gold nanorod solutions in the presence of sodium citrate.
AB  - In this study, the authors report that sodium citrate can aggregate hexadecyl
      trimethyl-ammonium ion(+)-coated gold nanorods (AuNRs), and nucleic acids of
      different charge and structure properties, i.e., single-stranded DNA (ssDNA),
      double-stranded DNA (dsDNA), single-stranded peptide nucleic acid (PNA), and PNA
      DNA complex, can bind to the AuNRs and therefore retard the sodium citrate
      induced aggregation to different extents. The discovery that hybridized dsDNA
      (and the PNA-DNA complex) has a more pronounced protection effect than ssDNA (and
      PNA) allows the authors to develop a homogeneous phase AuNRs-based UV-visible (UV
      vis) spectral assay for detecting specific sequences of oligonucleotides (20 mer)
      with a single-base-mismatch selectivity and a limit of detection of 5 nM. This
      assay involves no tedious bioconjugation and on-particle hybridization. The
      simple "set and test" format allows for a highly efficient hybridization in a
      homogeneous phase and a rapid display of the results in less than a minute. By
      measuring the degree of reduction in AuNR aggregation in the presence of
      different nucleic acid samples, one can assess how different nucleic acids
      interact with the AuNRs to complement the knowledge of spherical gold
      nanoparticles. Besides UV-vis characterization, transmission electron microscopy
      and zeta potential measurements were conduced to provide visual evidence of the
      particle aggregation and to support the discussion of the assay principle.

PMID- 21171721
TI  - Effect of contact angle hysteresis on the removal of the sporelings of the green
      alga Ulva from the fouling-release coatings synthesized from polyolefin polymers.
AB  - Wettability is one of the surface characteristics that is controlled by the
      chemical composition and roughness of a surface. A number of investigations have
      explored the relationship between water contact angle and surface free energy of
      polymeric coatings with the settlement (attachment) and adhesion strength of
      various marine organisms. However, the relationship between the contact angle
      hysteresis and fouling-release property is generally overlooked. In the present
      work, coatings were prepared by using commercial hydrophobic homopolymer and
      copolymer polyolefins, which have nearly the same surface free energy. The
      effects of contact angle hysteresis, wetting hysteresis, and surface free energy
      on the fouling-release properties for sporelings of the green alga Ulva from
      substrates were then examined quantitatively under a defined shear stress in a
      water channel. The ease of removal of sporelings under shear stress from the
      polymer surfaces was in the order of PP>HDPE>PPPE>EVA-12 and strongly and
      positively correlated with contact angle and wetting hysteresis; i.e., the higher
      the hysteresis, the greater the removal.

PMID- 21171722
TI  - Development of molecular simulation methods to accurately represent protein
      surface interactions: The effect of pressure and its determination for a system
      with constrained atoms.
AB  - When performing molecular dynamics simulations for a system with constrained
      (fixed) atoms, traditional isobaric algorithms (e.g., NPT simulation) often
      cannot be used. In addition, the calculation of the internal pressure of a system
      with fixed atoms may be highly inaccurate due to the nonphysical nature of the
      atomic constraints and difficulties in accurately defining the volume occupied by
      the unconstrained atoms in the system. The inability to properly set and control
      pressure can result in substantial problems for the accurate simulation of
      condensed-phase systems if the behavior of the system (e.g., peptide/protein
      adsorption) is sensitive to pressure. To address this issue, the authors have
      developed an approach to accurately determine the internal pressure for a system
      with constrained atoms. As the first step in this method, a periodically
      extendable portion of the mobile phase of the constrained system (e.g., the
      solvent atoms) is used to create a separate unconstrained system for which the
      pressure can be accurately calculated. This model system is then used to create a
      pressure calibration plot for an intensive local effective virial parameter for a
      small volume cross section or "slab" of the system. Using this calibration plot,
      the pressure of the constrained system can then be determined by calculating the
      virial parameter for a similarly sized slab of mobile atoms. In this article, the
      authors present the development of this method and demonstrate its application
      using the CHARMM molecular simulation program to characterize the adsorption
      behavior of a peptide in explicit water on a hydrophobic surface whose lattice
      spacing is maintained with atomic constraints. The free energy of adsorption for
      this system is shown to be dramatically influenced by pressure, thus emphasizing
      the importance of properly maintaining the pressure of the system for the
      accurate simulation of protein-surface interactions.

PMID- 21171723
TI  - Emotional granularity and borderline personality disorder.
AB  - This study examined the affective dysregulation component of borderline
      personality disorder (BPD) from an emotional granularity perspective, which
      refers to the specificity in which one represents emotions. Forty-six female
      participants meeting criteria for BPD and 51 female control participants without
      BPD and Axis I pathology completed tasks that assessed the degree to which
      participants incorporated information about valence (pleasant-unpleasant) and
      arousal (calm-activated) in their semantic/conceptual representations of emotions
      and in using labels to represent emotional reactions. As hypothesized,
      participants with BPD emphasized valence more and arousal less than control
      participants did when using emotion terms to label their emotional reactions.
      Implications and future research directions are discussed.

PMID- 21171724
TI  - Severe and nonsevere events in first onsets versus recurrences of depression:
      evidence for stress sensitization.
AB  - Overall, research has evidenced support for Post's (1992) model, which asserts
      that the 1st episode of depression is more likely to be associated with severe
      life events than are subsequent episodes. In spite of this, there are significant
      gaps in the understanding of the stress-depression association. This study aimed
      to address three gaps by (a) identifying the explanatory model underlying the
      association (stress sensitization vs. stress autonomy), (b) elucidating how the
      role of stress changes with successive episodes, and (c) examining the role of
      nonsevere events. The impact and occurrence of severe and nonsevere events in a 5
      year longitudinal study of late-adolescent women were examined using Cox
      regression models. Overall, we found support for the stress sensitization model
      over the stress autonomy model. Specifically, the impact of nonsevere (but not
      severe) events was greater in individuals with a history of depression compared
      with those with no history of depression. In addition, the occurrence of severe
      (but not nonsevere) events was greater for 1st onsets than recurrences. These
      effects were modified by event independence. The results were discussed in terms
      of the underlying mechanisms of the stress-depression association and future
      directions for research were elaborated.

PMID- 21171725
TI  - Dietary restraint moderates genetic risk for binge eating.
AB  - Dietary restraint is a prospective risk factor for the development of binge
      eating and bulimia nervosa. Although many women engage in dietary restraint,
      relatively few develop binge eating. Dietary restraint may increase
      susceptibility for binge eating only in individuals who are at genetic risk.
      Specifically, dietary restraint may be a behavioral exposure factor that
      activates genetic predispositions for binge eating. We investigated this
      possibility in 1,678 young adolescent and adult same-sex female twins from the
      Minnesota Twin Family Study and the Michigan State University Twin Registry. Twin
      moderation models were used to examine whether levels of dietary restraint
      moderate genetic and environmental influences on binge eating. Results indicated
      that genetic and nonshared environmental factors for binge eating increased at
      higher levels of dietary restraint. These effects were present after controlling
      for age, body mass index, and genetic and environmental overlap among dietary
      restraint and binge eating. Results suggest that dietary restraint may be most
      important for individuals at genetic risk for binge eating and that the
      combination of these factors could enhance individual differences in risk for
      binge eating.

PMID- 21171726
TI  - Type D personality and the development of PTSD symptoms: a prospective study.
AB  - Psychological trauma and prolonged stress may cause mental disorders such as
      posttraumatic stress disorder (PTSD). Pretrauma personality is an important
      determinant of posttraumatic adjustment. Specifically, trait neuroticism has been
      identified as a risk factor for PTSD. Additionally, the combination of high
      negative affectivity or neuroticism with marked social inhibition or
      introversion, also called Type D personality (Denollet, 2000), may compose a risk
      factor for PTSD. There is no research available that examined pretrauma Type D
      personality in relation to PTSD. The present study examined the predictive
      validity of the Type D personality construct in a sample of Dutch soldiers. Data
      were collected prior to and 6 months after military deployment to Afghanistan.
      Separate multiple regression analyses were performed to examine the predictive
      validity of Type D personality. First, Type D personality was defined as the
      interaction between negative affect and social inhibition (Na * Si). In a second
      analysis, Type D was defined following cutoff criteria recommended by Denollet
      (2000). Results showed that negative affectivity was a significant predictor of
      PTSD symptoms. Social inhibition and the interaction Na * Si did not add to the
      amount of explained variance in postdeployment PTSD scores over the effects of
      childhood abuse, negative affectivity, and prior psychological symptoms. A second
      analysis showed that Type D personality (dichotomous) did not add to the amount
      of explained variance in postdeployment PTSD scores over the effects of childhood
      abuse, and prior psychological symptoms. Therefore, Type D personality appears to
      be of limited value to explain development of combat-related PTSD symptoms.

PMID- 21171727
TI  - Imagining the future: degraded representations of future rewards and events in
      schizophrenia.
AB  - Over the course of life, most people work toward temporally distant rewards such
      as university degrees or work-related promotions. In contrast, many people with
      schizophrenia show deficits in behavior oriented toward long-term rewards,
      although they function adequately when rewards are more immediately present.
      Moreover, when asked about possible future events, individuals with schizophrenia
      show foreshortened future time perspectives relative to healthy individuals.
      Here, we take the view that these deficits are related and can be explained by
      cognitive deficits. We compared the performance of participants with
      schizophrenia (n = 39) and healthy participants (n = 25) on tasks measuring
      reward discounting and future event representations. Consistent with previous
      research, we found that relative to healthy participants, those with
      schizophrenia discounted the value of future rewards more steeply. Furthermore,
      when asked about future events, their responses were biased toward events in the
      near future, relative to healthy participants' responses. Although discounting
      and future representations were unrelated in healthy participants, we found
      significant correlations across the tasks among participants with schizophrenia,
      as well as correlations with cognitive variables and symptoms. Further analysis
      showed that statistically controlling working memory eliminated group differences
      in task performance. Together these results suggest that the motivational
      deficits characteristic of schizophrenia relate to cognitive deficits affecting
      the ability to represent and/or evaluate distant outcomes, a finding with
      important implications for promoting recovery from schizophrenia.

PMID- 21171729
TI  - Think crisis-think female: the glass cliff and contextual variation in the think
      manager-think male stereotype.
AB  - The "think manager-think male" (TMTM) association underlies many gender
      inequalities in the workplace. However, research into the "glass cliff" has
      demonstrated that the suitability of male and female managers varies as a
      function of company performance such that in times of poor performance people may
      "think female" (Ryan & Haslam, 2005, 2007). Three studies examined gender and
      managerial stereotypes in the context of companies that are doing well or doing
      badly. Study 1 reproduced TMTM associations for descriptions of managers of
      successful companies but demonstrated a reversal for managers of unsuccessful
      companies. Study 2 examined the prescriptive nature of these stereotypes. No TMTM
      relationship was found for ideal managers of successful companies, but ideal
      managers of unsuccessful companies were associated with the female stereotype.
      Study 3 suggested that women may be favored in times of poor performance, not
      because they are expected to improve the situation, but because they are seen to
      be good people managers and can take the blame for organizational failure.
      Together, the studies illustrate the importance of context as a moderator of the
      TMTM association. Practical and theoretical implications for gender
      discrimination in the workplace are discussed.

PMID- 21171730
TI  - Motivating and demotivating forces in teams: cross-level influences of empowering
      leadership and relationship conflict.
AB  - Using cross-cultural laboratory and field studies with samples of leaders,
      employees, and students from the United States and the People's Republic of
      China, we examined how team-level stimuli, including empowering leadership and
      relationship conflict, combine to influence individual members' motivational
      states of psychological empowerment and affective commitment. As predicted, we
      found that these motivational states are individually and jointly influenced by
      teams' level of empowering leadership and relationship conflict and that these
      motivational states mediate the relationships between team stimuli and team
      members' innovative and teamwork behaviors and turnover intentions. In addition,
      results held despite controlling for team members' nationality and collectivism.
      We discuss contributions of our study to the team motivation, conflict, and
      stress literatures.

PMID- 21171728
TI  - Interactions between early parenting and a polymorphism of the child's dopamine
      transporter gene in predicting future child conduct disorder symptoms.
AB  - Mounting evidence suggests that genetic risks for mental disorders often interact
      with the social environment, but most studies still ignore environmental
      moderation of genetic influences. The authors tested interactions between
      maternal parenting and the variable number tandem repeat (VNTR) polymorphism in
      the 3' untranslated region of the dopamine transporter gene in the child to
      increase understanding of gene-environment interactions involving early
      parenting. Participants were part of a 9-year longitudinal study of 4- to 6-year
      old children who met criteria for attention-deficit/hyperactivity disorder (ADHD)
      and demographically matched controls. Maternal parenting was observed during
      standard mother-child interactions in Wave 1. The child's conduct disorder (CD)
      symptoms 5-8 years later were measured using separate structured diagnostic
      interviews of the mother and youth. Controlling for ADHD symptoms and child
      disruptive behavior during the mother-child interaction, there was a significant
      inverse relation between levels of both positive and negative parenting at 4-6
      years and the number of later CD symptoms, but primarily among children with 2
      copies of the 9-repeat allele of the VNTR. The significant interaction with
      negative parenting was replicated in parent and youth reports of CD symptoms
      separately.

PMID- 21171731
TI  - Service without a smile: comparing the consequences of neutral and positive
      display rules.
AB  - We used an experimental design to examine the intrapersonal and interpersonal
      processes through which neutral display rules, compared to positive display
      rules, influence objective task performance of poll workers and ratings provided
      by survey respondents of the poll workers. Student participants (N = 140) were
      trained to adhere to 1 of the 2 display rule conditions while delivering opinion
      surveys to potential patrons of an organization during a 40-min period. Results
      showed that, compared to positive display rules, neutral display rules resulted
      in less task persistence and greater avoidance behavior. These effects were
      mediated through a greater use of expression suppression. In addition, neutral
      display rules resulted in less positive respondent mood, which accounted for
      lower ratings of service quality and of overall favorability attitudes toward the
      sponsoring organization. The importance and ubiquity of neutral display rules are
      discussed, given the potential for positive and negative consequences at work.

PMID- 21171732
TI  - Safety at work: a meta-analytic investigation of the link between job demands,
      job resources, burnout, engagement, and safety outcomes.
AB  - In this article, we develop and meta-analytically test the relationship between
      job demands and resources and burnout, engagement, and safety outcomes in the
      workplace. In a meta-analysis of 203 independent samples (N = 186,440), we found
      support for a health impairment process and for a motivational process as
      mechanisms through which job demands and resources relate to safety outcomes. In
      particular, we found that job demands such as risks and hazards and complexity
      impair employees' health and positively relate to burnout. Likewise, we found
      support for job resources such as knowledge, autonomy, and a supportive
      environment motivating employees and positively relating to engagement. Job
      demands were found to hinder an employee with a negative relationship to
      engagement, whereas job resources were found to negatively relate to burnout.
      Finally, we found that burnout was negatively related to working safely but that
      engagement motivated employees and was positively related to working safely.
      Across industries, risks and hazards was the most consistent job demand and a
      supportive environment was the most consistent job resource in terms of
      explaining variance in burnout, engagement, and safety outcomes. The type of job
      demand that explained the most variance differed by industry, whereas a
      supportive environment remained consistent in explaining the most variance in all
      industries.

PMID- 21171733
TI  - Paying a price: culture, trust, and negotiation consequences.
AB  - Three studies contrasting Indian and American negotiators tested hypotheses
      derived from theory proposing why there are cultural differences in trust and how
      cultural differences in trust influence negotiation strategy. Study 1 (a survey)
      documented that Indian negotiators trust their counterparts less than American
      negotiators. Study 2 (a negotiation simulation) linked American and Indian
      negotiators' self-reported trust and strategy to their insight and joint gains.
      Study 3 replicated and extended Study 2 using independently coded negotiation
      strategy data, allowing for stronger causal inference. Overall, the strategy
      associated with Indian negotiators' reluctance to extend interpersonal (as
      opposed to institutional) trust produced relatively poor outcomes. Our data
      support an expanded theoretical model of negotiation, linking culture to trust,
      strategies, and outcomes.

PMID- 21171734
TI  - Harming high performers: a social comparison perspective on interpersonal harming
      in work teams.
AB  - This study developed a multilevel model of the interpersonal harming behavior
      associated with social comparison processes in work teams. We tested this model
      using temporally lagged data from a sample of student teams (Study 1) and cross
      sectional data from a sample of work teams in a telecommunication services
      company (Study 2). In both studies, social relations analyses revealed that in
      teams with less cooperative goals, comparison to a higher performing team member
      was positively associated with interpersonal harming behavior, but only when
      expectations of future performance similarity to that member were low. The
      interactive relationship of social comparison and expected future performance
      similarity with interpersonal harming was buffered, however, in teams with more
      cooperative goals.

PMID- 21171735
TI  - Why seeking help from teammates is a blessing and a curse: a theory of help
      seeking and individual creativity in team contexts.
AB  - Research has not explored the extent to which seeking help from teammates
      positively relates to a person's own creativity. This question is important to
      explore as help seeking is commonly enacted in organizations and may come with
      reciprocation costs that may also diminish creativity. Results based on 291
      employees in a single division of a large multinational organization revealed
      that seeking help predicted creativity and mediated the relationship between
      intrinsic motivation and creativity. However, help seekers also incurred
      reciprocation costs in that they tended to give more help to teammates, and
      giving help to teammates was negatively related to creativity. In general, giving
      higher levels of help attenuated the positive relationship between help seeking
      and creativity. We also tested an integrated model to show that help giving
      moderated the mediated relationship between intrinsic motivation and creativity
      via help seeking, such that higher levels of help giving attenuated this mediated
      effect. We discuss theoretical and practical implications recommending additional
      research regarding the interpersonal creative process in team contexts.

PMID- 21171736
TI  - Adaptation and validation of the Spanish-language Trauma Symptom Inventory in
      Puerto Rico.
AB  - OBJECTIVE: This research was conducted to assess the Spanish-language Trauma
      Symptom Inventory's (Briere, 1995) suitability for use with a Puerto Rican
      sample. Minor revisions were made to the original instrument following a
      comprehensive appraisal involving a bilingual committee and pilot focus group.
      The present study outlines the review and adaptation process and examines the
      psychometric properties of the revised instrument, the Inventario de Sintomas de
      Trauma-Revisado (IST-R). METHOD: A sample of 225 students (155 women, 70 men) at
      the University of Puerto Rico, age 20 to 59 (M = 23.24, SD = 4.69), participated
      in the validation study. Participants completed a demographic questionnaire; a
      self-report trauma exposure instrument; and measures of psychological distress,
      including Spanish-language versions of the Beck Depression Inventory, Symptom
      Checklist-36, and the Dissociative Experiences Scale. RESULTS: Reliability
      coefficients for the IST-R clinical scales ranged from .69 to .91 (mean alpha =
      .84), and correlation coefficients were strongest for scales measuring the same
      constructs. Factor loadings obtained were consistent with those reported in the
      literature. Results support the internal consistency and construct validity of
      the IST-R. CONCLUSIONS: Culturally and linguistically appropriate assessment
      instruments are needed to address the mental health needs of diverse populations.
      Results from this study provide evidence for the clinical and research promise of
      the IST-R as a screening tool for trauma-related symptoms.

PMID- 21171737
TI  - Making self-help more helpful: a randomized controlled trial of the impact of
      augmenting self-help materials with implementation intentions on promoting the
      effective self-management of anxiety symptoms.
AB  - OBJECTIVE: The effectiveness of self-help materials may be constrained by
      failures to undertake recommended exercises or to deploy the techniques that one
      has learned at the critical moment. The present randomized controlled trial
      investigated whether augmenting self-help materials with if-then plans (or
      implementation intentions) could overcome these problems and enhance the self
      management of anxiety symptoms. METHOD: At baseline, participants who reported
      anxiety symptoms completed the Hospital Anxiety and Depression Scale (HADS) and
      the state version of the State-Trait Anxiety Inventory (STAI). Participants were
      then randomized via a computer program to standard self-help (n = 86), augmented
      self-help (n = 90), or no-intervention (n = 86) conditions. Eight weeks later,
      95% (n = 249) of the participants completed the HADS and STAI again. RESULTS:
      Findings showed a significant reduction in anxiety in the augmented self-help
      condition compared with both the standard self-help and no-intervention
      conditions (caseness rates on the HADS at follow-up were 21%, 49%, and 44%,
      respectively). Mediation analyses indicated that the benefits of augmented self
      help materials were explained by improved detection of anxiety-related triggers
      and greater experienced benefits of the self-help techniques. CONCLUSIONS: These
      findings suggest that implementation intentions offer a valuable supplement to
      self-help materials that can enhance their impact on outcomes.

PMID- 21171738
TI  - A combined motivation and parent-child interaction therapy package reduces child
      welfare recidivism in a randomized dismantling field trial.
AB  - OBJECTIVE: A package of parent-child interaction therapy (PCIT) combined with a
      self-motivational (SM) orientation previously was found in a laboratory trial to
      reduce child abuse recidivism compared with services as usual (SAU). Objectives
      of the present study were to test effectiveness in a field agency rather than in
      a laboratory setting and to dismantle the SM versus SAU orientation and PCIT
      versus SAU parenting component effects. METHOD: Participants were 192 parents in
      child welfare with an average of 6 prior referrals and most with all of their
      children removed. Following a 2 x 2 sequentially randomized experimental design,
      parents were randomized first to orientation condition (SM vs. SAU) and then
      subsequently randomized to a parenting condition (PCIT vs. SAU). Cases were
      followed for child welfare recidivism for a median of 904 days. An imputation
      based approach was used to estimate recidivism survival complicated by
      significant treatment-related differences in timing and frequency of children
      returned home. RESULTS: A significant orientation condition by parenting
      condition interaction favoring the SM + PCIT combination was found for reducing
      future child welfare reports, and this effect was stronger when children were
      returned to the home sooner rather than later. CONCLUSIONS: Findings demonstrate
      that previous laboratory results can be replicated in a field implementation
      setting and among parents with chronic and severe child welfare histories,
      supporting a synergistic SM + PCIT benefit. Methodological considerations for
      analyzing child welfare event history data complicated by differential risk
      deprivation are also emphasized.

PMID- 21171739
TI  - The latent structure of life-course-persistent antisocial behavior: is Moffitt's
      developmental taxonomy a true taxonomy?
AB  - OBJECTIVE: The purpose of this study was to determine whether life-course
      persistent (LCP) and adolescence-limited (AL) antisocial behavior form distinct
      categories or lie along a common dimension. METHOD: Taxometric analyses were
      performed on 2,175 men and women from the National Longitudinal Survey of Youth
      Child Data (Center for Human Resource Research, 2009) with at least 1 self
      reported delinquent act. The 3 externalizing factor scales from the parent-rated
      Behavior Problems Index (Peterson & Zill, 1986)--Antisocial, Headstrong, and
      Hyperactive--served as indicators in an investigation into the latent structure
      of LCP and AL antisocial behavior. RESULTS: All 3 taxometric procedures included
      in this study--mean above minus below a cut, maximum covariance, and latent mode
      factor analysis-produced results consistent with the conclusion that the latent
      structure of LCP and AL antisocial behavior is dimensional in nature. CONCLUSION:
      From a conceptual standpoint, the results of this study suggest that LCP and AL
      antisocial behavior differ in degree (quantitative difference) rather than in
      kind (qualitative difference). These results have potentially important
      implications for theory development as well as for clinical assessment,
      diagnosis, and intervention.

PMID- 21171740
TI  - Stigma, social context, and mental health: lesbian and gay couples across the
      transition to adoptive parenthood.
AB  - This is the first study to examine change in depression and anxiety across the
      first year of adoptive parenthood in same-sex couples (90 couples: 52 lesbian, 38
      gay male). Given that sexual minorities uniquely contend with sexual orientation
      related stigma, this study examined how both internalized and enacted forms of
      stigma affect the mental health of lesbians and gay men during the transition to
      parenthood. In addition, the role of contextual support was examined. Higher
      perceived workplace support, family support, and relationship quality were
      related to lower depressive and anxious symptoms at the time of the adoption, and
      higher perceived friend support was related to lower anxiety symptoms. Lower
      internalized homophobia and higher perceived neighborhood gay-friendliness were
      related to lower depressive symptoms. Finally, individuals with high internalized
      homophobia who lived in states with unfavorable legal climates regarding gay
      adoption experienced the steepest increases in depressive and anxious symptoms.
      Findings have important implications for counselors working with sexual
      minorities, especially those experiencing the transition to parenthood.

PMID- 21171741
TI  - Deconstructing multicultural counseling competencies research: comment on Owen,
      Leach, Wampold, and Rodolfa (2011).
AB  - The present article offers a commentary and critique of the research presented by
      J. Owen, M. M. Leach, B. Wampold and E. Rodolfa (2011). Given the complexity of
      the research methodology, findings, and conclusions, the authors provide a
      concise summary of findings, study limitations, and conclusions followed by a
      detailed critique of the study. The authors respect and appreciate the ambitious
      efforts made by Owen et al. to address gaps in the literature regarding outcome
      research using client ratings of counselors' multicultural counseling
      competencies (MCCs). The authors provide a critical analysis of some of J. Owen
      et al.'s specific conclusions and offer alternative conclusions based on
      conceptual and methodological bases. The authors use the opportunity to comment
      on this study as a means of advancing recommendations regarding future research
      on MCCs that might contribute to substantive revisions to the long-standing
      theoretical foundation in this area.

PMID- 21171742
TI  - Dimensions of acculturation: associations with health risk behaviors among
      college students from immigrant families.
AB  - In the present study, we examined a bidimensional model of acculturation (which
      includes both heritage and U.S. practices, values, and identifications) in
      relation to hazardous alcohol use, illicit drug use, unsafe sexual behavior, and
      impaired driving. A sample of 3,251 first- and second-generation immigrant
      students from 30 U.S. colleges and universities completed measures of behavioral
      acculturation; cultural values (individualism, collectivism, and self-construal);
      ethnic and U.S. identity; and patterns of alcohol and drug use, engagement in
      potentially unsafe sexual activities, and driving while (or riding with a driver
      who was) intoxicated. Results indicate that heritage practices and collectivist
      values were generally protective against health risk behaviors, with collectivist
      values most strongly and consistently protective. Nonetheless, heritage
      identifications were positively associated with sexual risk taking for Hispanics.
      U.S. practices, values, and identifications were not consistently related to risk
      behavior participation. Results are discussed in terms of bidimensional
      approaches to acculturation, the immigrant paradox, and implications for
      counseling practice.

PMID- 21171744
TI  - Multicultural approaches in psychotherapy: A rejoinder.
AB  - In this rejoinder, the authors address several issues raised by R. L. Worthington
      and F. R. Dillon (2011) and C. R. Ridley and M. Shaw-Ridley (2011) regarding (a)
      the measurement of multicultural competencies (MCCs), (b) sampling considerations
      in multicultural research, and (c) the conceptual frame of multicultural
      psychotherapy research. The authors challenge the wisdom of exploring MCCs in
      psychotherapy research and provide a different framework to understand
      therapists' multicultural effectiveness with clients based on their cultural
      race/ethnicity. Additionally, the concept of therapists' multicultural
      orientation or approach is introduced to illuminate the process of aligning with
      clients about salient cultural issues in psychotherapy. (PsycINFO Database Record
      (c) 2010 APA, all rights reserved).

PMID- 21171743
TI  - Race/ethnicity, color-blind racial attitudes, and multicultural counseling
      competence: the moderating effects of multicultural counseling training.
AB  - Increasing trainees' multicultural counseling competence (MCC) has been a hot
      topic in counseling. Scholars have identified predictors (e.g., race/ethnicity,
      color-blindness) of MCC, and educators provide multicultural training for
      trainees. Using a sample of 370 psychology trainees, this study examined whether
      multicultural training (a) moderated racial/ethnic differences on MCC and (b)
      changed the relationship between color-blindness and MCC. Results indicated a
      significant interaction effect of race/ethnicity (i.e., White vs. ethnic
      minority) and multicultural training on multicultural awareness, but not on
      multicultural knowledge. Specifically, at lower levels of training, racial/ethnic
      minority trainees had significantly higher multicultural awareness than their
      White counterparts; at higher levels of training, no significant difference was
      found. Described differently, more training significantly enhanced Whites'
      multicultural awareness, but did not enhance racial/ethnic minority trainees'
      awareness. Additionally, there was a significant interaction effect of color
      blindness and multicultural training on multicultural knowledge, but not on
      multicultural awareness. The association between color-blindness and
      multicultural knowledge was stronger at higher levels of multicultural training
      than at lower levels of training. Alternatively, the effect of training on
      enhancing knowledge was stronger for those with lower color-blindness than for
      those with higher color-blindness.

PMID- 21171745
TI  - Ethnic identity and personal well-being of people of color: a meta-analysis.
AB  - This article summarizes research examining the relationship between the
      constructs of ethnic identity and personal well-being among people of color in
      North America. Data from 184 studies analyzed with random effects models yielded
      an omnibus effect size of r = .17, suggesting a modest relationship between the 2
      constructs. The relationship was somewhat stronger among adolescents and young
      adults than among adults over age 40. No differences were observed across
      participant race, gender, or socioeconomic status, which findings support the
      general relevance of ethnic identity across people of color. Studies correlating
      ethnic identity with self-esteem and positive well-being yielded average effect
      sizes twice as large as those from studies correlating ethnic identity with
      personal distress or mental health symptoms. Ethnic identity was thus more
      strongly related to positive well-being than to compromised well-being. Overall,
      the corpus of research reviewed consisted of correlational designs; limited
      scholarship has addressed causal mechanisms, mediating factors, or psychological
      functions of ethnic identity across different social contexts.

PMID- 21171746
TI  - The impact of school-based mentoring on youths with different relational
      profiles.
AB  - Associations between youths' relationship profiles and mentoring outcomes were
      explored in the context of a national, randomized study of 1,139 youths (54%
      female) in geographically diverse Big Brothers Big Sisters school-based mentoring
      programs. The sample included youths in Grades 4-9 from diverse racial and ethnic
      backgrounds, the majority of whom were receiving free or reduced-price lunch.
      Latent profile analysis, a person-oriented approach, was used to identify 3
      distinct relational profiles. Mentoring was found to have differential effects
      depending on youths' preintervention approach to relationships. In particular,
      youths who, at baseline, had satisfactory, but not particularly strong,
      relationships benefited more from mentoring than did youths with profiles
      characterized by either strongly positive or negative relationships. Implications
      for research and practice are discussed.

PMID- 21171747
TI  - Stability and change in adolescent spirituality/religiosity: a person-centered
      approach.
AB  - Although there has been a substantial increase over the past decade in studies
      that have examined the psychosocial correlates of spirituality/religiosity in
      adolescence, very little is known about spirituality/religiosity as a domain of
      development in its own right. To address this limitation, the authors identified
      configurations of multiple dimensions of spirituality/religiosity across 2 time
      points with an empirical classification procedure (cluster analysis) and assessed
      development in these configurations at the sample and individual level.
      Participants included 756 predominately Canadian-born adolescents (53% female,
      47% male) from southern Ontario, Canada, who completed a survey in Grade 11 (M
      age = 16.41 years) and Grade 12 (M age = 17.36 years). Measures included
      religious activity involvement, enjoyment of religious activities, the Spiritual
      Transcendence Index, wondering about spiritual issues, frequency of prayer, and
      frequency of meditation. Sample-level development (structural stability and
      change) was assessed by examining whether the structural configurations of the
      clusters were consistent over time. Individual-level development was assessed by
      examining intraindividual stability and change in cluster membership over time.
      Results revealed that a five cluster-solution was optimal at both grades.
      Clusters were identified as aspiritual/irreligious, disconnected wonderers, high
      institutional and personal, primarily personal, and meditators. With the
      exception of the high institutional and personal cluster, the cluster structures
      were stable over time. There also was significant intraindividual stability in
      all clusters over time; however, a significant proportion of individuals
      classified as high institutional and personal in Grade 11 moved into the
      primarily personal cluster in Grade 12.

PMID- 21171748
TI  - A dimensional approach to maternal attachment state of mind: relations to
      maternal sensitivity and maternal autonomy support.
AB  - The aim of this study was to examine the developmental significance of the newly
      developed dimensional approach to attachment state of mind by investigating its
      capacity to predict individual differences in the quality of two caregiving
      behaviors-maternal sensitivity and maternal autonomy support-that are linked to
      numerous important child outcomes. Seventy-one upper-middle-class, predominantly
      French-speaking and Caucasian dyads participated in 3 home visits (34 girls). The
      Adult Attachment Interview (AAI) was administered when the infants were 8 months
      old, maternal sensitivity was assessed when they were 12 months old, and maternal
      autonomy support was assessed at 15 months. The results revealed that, above and
      beyond SES, maternal sensitivity was negatively related to the dismissing
      dimension of the AAI, whereas maternal autonomy support was negatively linked to
      the preoccupied/unresolved dimension. In contrast, the traditional AAI categories
      were not significantly linked to parenting. These results speak to the relevance
      of using a continuous approach to attachment state of mind when predicting
      individual differences in specific caregiving behaviors.

PMID- 21171749
TI  - Age-related differences in profiles of mood-change trajectories.
AB  - As a group, older adults report positive affective lives. The extent to which
      there are subgroups of older adults whose moods are less positive, however, is
      unclear. Our aim in the present study was to identify and characterize different
      subgroups of adults who exhibit distinct trajectories of mood change across a
      relatively short time period. Seventy-nine young and 103 older adults
      continuously reported their moods while viewing emotional and neutral faces.
      Cluster analysis revealed four subgroups of mood-change trajectories. Both the
      most positive and the most negative subgroups included more older than young
      adults (ps < .05), suggesting that not all older adults exhibit higher positive
      affect than young adults. Analyses of variance revealed that the most negative
      group exhibited slower processing speed, more state anxiety and neuroticism, and
      looked less at happy faces than the other groups (ps < .05). The results are
      discussed from an adult developmental perspective, focusing on the increased
      variability of mood trajectories in the older adults and whether this is a
      reflection of adaptive functioning or a potential harbinger of dysfunction.

PMID- 21171751
TI  - Twelfth-grade student work intensity linked to later educational attainment and
      substance use: new longitudinal evidence.
AB  - Long hours of paid employment during high school have been linked to a variety of
      problem behaviors, but questions remain about whether and to what extent work
      intensity makes any causal contribution. This study addresses those questions by
      focusing on how 12th-grade work intensity is associated with substance use and
      educational attainment in the years following high school. It uses 2 nationally
      representative longitudinal data sets from the Monitoring the Future project,
      spanning a total of 3 decades. One data set tracks 8th graders for 8 years (modal
      ages 14-22) and provides extensive controls for possible prior causes; the
      second, larger data set tracks 12th graders for up to 12 years (to modal ages 29
      30) and permits assessment of possible short-term and longer term consequences.
      Findings based on propensity score matching and multivariate regression analyses
      are highly consistent across the 2 sets of data. All findings show that more
      fundamental prior problems, including low academic performance and aspirations,
      make substantial contributions to substance use and long-term academic attainment
      (selection effects), but the findings also suggest that high work intensity
      during high school has long-term costs in terms of college completion and perhaps
      cigarette use.

PMID- 21171750
TI  - Atypical EEG power correlates with indiscriminately friendly behavior in
      internationally adopted children.
AB  - While effects of institutional care on behavioral development have been studied
      extensively, effects on neural systems underlying these socioemotional and
      attention deficits are only beginning to be examined. The current study assessed
      electroencephalogram (EEG) power in 18-month-old internationally adopted,
      postinstitutionalized children (n = 37) and comparison groups of nonadopted
      children (n = 47) and children internationally adopted from foster care (n = 39).
      For their age, postinstitutionalized children had an atypical EEG power
      distribution, with relative power concentrated in lower frequency bands compared
      with nonadopted children. Both internationally adopted groups had lower absolute
      alpha power than nonadopted children. EEG power was not related to growth at
      adoption or to global cognitive ability. Atypical EEG power distribution at 18
      months predicted indiscriminate friendliness and poorer inhibitory control at 36
      months. Both postinstitutionalized and foster care children were more likely than
      nonadopted children to exhibit indiscriminate friendliness. Results are
      consistent with a cortical hypoactivation model of the effects of early
      deprivation on neural development and provide initial evidence associating this
      atypical EEG pattern with indiscriminate friendliness. Outcomes observed in the
      foster care children raise questions about the specificity of institutional
      rearing as a risk factor and emphasize the need for broader consideration of the
      effects of early deprivation and disruptions in care.

PMID- 21171752
TI  - The import of the cortisol rise in child care differs as a function of behavioral
      inhibition.
AB  - Children of ages 3 to 4.5 years (N = 107; 45 boys, 62 girls) were studied twice,
      6 months apart, to examine whether the cortisol rise in child care at Time 1 (T1)
      was associated with (a) changes in anxious, vigilant behavior from T1 to Time 2
      (T2) and (b) higher internalizing symptoms at T2. Controlling for measures of
      home environment and child care quality at T1, as well as for cortisol activity
      at T2, we obtained results indicating that behavioral inhibition moderated the
      associations between the rise in cortisol at T1 and child outcomes at T2 (i.e.,
      anxious, vigilant behavior and internalizing symptoms). For both outcomes, the
      rise in cortisol at T1 became more positively predictive at increasing levels of
      behavioral inhibition. Specifically, at higher levels of behavioral inhibition,
      children with larger T1 cortisol increases expressed more internalizing symptoms
      than did children at lower levels of behavioral inhibition; in contrast, for
      those with low cortisol activity at T1, children with higher levels of inhibition
      expressed fewer internalizing symptoms than did children at lower levels of
      inhibition. In addition, children with higher levels of behavioral inhibition and
      lower cortisol activity at T1 exhibited reductions in anxious, vigilant behavior
      from T1 to T2, whereas at lower levels of behavioral inhibition, variations in
      the T1 cortisol rise bore no relation to changes in this behavior. These results
      suggest that the rise in cortisol at child care may have differential predictive
      value as a function of behaviorally inhibited temperament.

PMID- 21171754
TI  - Shifts in attention biases in response to acute pain induction: examination of a
      model of "conversion" among repressors.
AB  - Unlike most people, those who are characterized by a repressive coping style
      report high levels of physical (sensory) pain but low levels of emotional
      distress (affective pain), which is a discrepancy that may suggest a "conversion"
      process. In two studies, we tested an attention allocation model, proposing that
      repressors direct attention away from threatening negative affective information
      and toward nonthreatening physical pain information during emotionally arousing
      (painful) situations. In Study 1, 84 participants underwent a cold pressor and
      then recovered. Repressors reported greater pain during recovery than low- and
      high-anxious participants, but they reported lower distress than high-anxious
      participants. Repressors reported significant and large discrepancies between
      high pain and low distress, whereas these differences were less pronounced for
      other groups. In Study 2, 77 participants underwent an ischemic pain task while
      performing a modified dot-probe task with sensory and negative affective pain
      words as stimuli. Repressors showed increasing biases away from affective pain
      words and toward sensory pain words as the pain task continued, whereas low- and
      high-anxious participants did not show these shifts in attention. The results
      support the notion that conversion among repressors may involve a process by
      which attention is directed away from emotional distress during noxious
      stimulation and is focused instead on sensory information from pain.

PMID- 21171753
TI  - Trajectories of emotional well-being in mothers of adolescents and adults with
      autism.
AB  - Raising an adolescent or adult child with a developmental disability confers
      exceptional caregiving challenges on parents. We examined trajectories of 2
      indicators of emotional well-being (depressive symptoms and anxiety) in a sample
      of primarily Caucasian mothers (N = 379; M age = 51.22 years at Time 1) of
      adolescent and adult children with an autism spectrum disorder (ASD; M age =
      21.91 years at Time 1, 73.2% male). We also investigated within-person
      associations of child context time-varying covariates (autism symptoms, behavior
      problems, residential status) and maternal context time-varying covariates
      (social support network size and stressful family events) with the trajectories
      of emotional well-being. Data were collected on 5 occasions across a 10-year
      period. Average patterns of stable (depressive symptoms) and improved (anxiety)
      emotional well-being were evident, and well-being trajectories were sensitive to
      fluctuations in both child and maternal context variables. On occasions when
      behavior problems were higher, depressive symptoms and anxiety were higher. On
      occasions after which the grown child moved out of the family home, anxiety was
      lower. Anxiety was higher on occasions when social support networks were smaller
      and when more stressful life events were experienced. These results have
      implications for midlife and aging families of children with an ASD and those who
      provide services to these families.

PMID- 21171755
TI  - Playing prosocial video games increases empathy and decreases schadenfreude.
AB  - Past research provided abundant evidence that exposure to violent video games
      increases aggressive tendencies and decreases prosocial tendencies. In contrast,
      research on the effects of exposure to prosocial video games has been relatively
      sparse. The present research found support for the hypothesis that exposure to
      prosocial video games is positively related to prosocial affect and negatively
      related to antisocial affect. More specifically, two studies revealed that
      playing a prosocial (relative to a neutral) video game increased interpersonal
      empathy and decreased reported pleasure at another's misfortune (i.e.,
      schadenfreude). These results lend further credence to the predictive validity of
      the General Learning Model (Buckley & Anderson, 2006) for the effects of media
      exposure on social tendencies.

PMID- 21171756
TI  - The influence of emotion regulation on social interactive decision-making.
AB  - Although adequate emotion regulation is considered to be essential in every day
      life, it is especially important in social interactions. However, the question as
      to what extent two different regulation strategies are effective in changing
      decision-making in a consequential socially interactive context remains
      unanswered. We investigated the effect of expressive suppression and emotional
      reappraisal on strategic decision-making in a social interactive task, that is,
      the Ultimatum Game. As hypothesized, participants in the emotional reappraisal
      condition accepted unfair offers more often than participants in the suppression
      and no-regulation condition. Additionally, the effect of emotional reappraisal
      influenced the amount of money participants proposed during a second interaction
      with partners that had treated them unfairly in a previous interaction. These
      results support and extend previous findings that emotional reappraisal as
      compared to expressive suppression, is a powerful regulation strategy that
      influences and changes how we interact with others even in the face of inequity.

PMID- 21171758
TI  - Discourse-based emotional consistency modulates early and middle components of
      event-related potentials.
AB  - In this study, participants read stories describing emotional episodes with
      either a positive or negative valence (Experiment 1). Following each story,
      participants were exposed to short sentences referring to the protagonist, and
      the event-related potential (ERP) for each sentence's last word was recorded.
      Some sentences described the protagonist's emotion, either consistent or
      inconsistent with the story; others were neutral; and others involved a
      semantically anomalous word. Inconsistent emotions were found to elicit larger
      N100/P200 and N400 than consistent emotions. However, when participants were
      exposed to the same critical sentences in a control experiment (Experiment 2) in
      which the stories had been removed, emotional consistency effects disappeared in
      all ERP components, demonstrating that these effects were discourse-level
      phenomena. By contrast, the ordinary N400 effect for locally anomalous words in
      the sentence was obtained both with and without story context. In conclusion,
      reading stories describing events with emotional significance determines strong
      and very early anticipations of an emotional word.

PMID- 21171757
TI  - Impulsive choice and altruistic punishment are correlated and increase in tandem
      with serotonin depletion.
AB  - Human cooperation may partly depend on the presence of individuals willing to
      incur personal costs to punish noncooperators. The psychological factors that
      motivate such 'altruistic punishment' are not fully understood; some have argued
      that altruistic punishment is a deliberate act of norm enforcement that requires
      self-control, while others claim that it is an impulsive act driven primarily by
      emotion. In the current study, we addressed this question by examining the
      relationship between impulsive choice and altruistic punishment in the ultimatum
      game. As the neurotransmitter serotonin has been implicated in both impulsive
      choice and altruistic punishment, we investigated the effects of manipulating
      serotonin on both measures. Across individuals, impulsive choice and altruistic
      punishment were correlated and increased following serotonin depletion. These
      findings imply that altruistic punishment reflects the absence rather than the
      presence of self control, and suggest that impulsive choice and altruistic
      punishment share common neural mechanisms.

PMID- 21171759
TI  - Evidence and a computational explanation of cultural differences in facial
      expression recognition.
AB  - Facial expressions are crucial to human social communication, but the extent to
      which they are innate and universal versus learned and culture dependent is a
      subject of debate. Two studies explored the effect of culture and learning on
      facial expression understanding. In Experiment 1, Japanese and U.S. participants
      interpreted facial expressions of emotion. Each group was better than the other
      at classifying facial expressions posed by members of the same culture. In
      Experiment 2, this reciprocal in-group advantage was reproduced by a
      neurocomputational model trained in either a Japanese cultural context or an
      American cultural context. The model demonstrates how each of us, interacting
      with others in a particular cultural context, learns to recognize a culture
      specific facial expression dialect.

PMID- 21171760
TI  - Interpretation training influences memory for prior interpretations.
AB  - Anxiety is associated with memory biases when the initial interpretation of the
      event is taken into account. This experiment examined whether modification of
      interpretive bias retroactively affects memory for prior events and their initial
      interpretation. Before training, participants imagined themselves in emotionally
      ambiguous scenarios to which they provided endings that often revealed their
      interpretations. Then they were trained to resolve the ambiguity in other
      situations in a consistently positive (n = 37) or negative way (n = 38) before
      they tried to recall the initial scenarios and endings. Results indicated that
      memory for the endings was imbued with the emotional tone of the training,
      whereas memory for the scenarios was unaffected.

PMID- 21171761
TI  - The effect of expectancy of a threatening event on time perception in human
      adults.
AB  - Two experiments were conducted to investigate the effect of a threatening
      stimulus in human adults in a temporal bisection task. In Experiment 1, for two
      anchor duration conditions (400/800 vs. 800/1600 ms), the participants completed
      trials in which the probe duration was followed by an aversive stimulus or a
      nonaversive stimulus. The results showed that the duration was judged longer when
      the participants expected an aversive rather than a nonaversive stimulus. In
      Experiment 2, the effect of the temporal localization of the aversive stimulus
      was also tested, with the aversive stimulus being presented at the beginning or
      at the end of the probe duration. The results revealed a temporal overestimation
      in each condition compared to the trials in which no aversive stimulus was
      presented. Furthermore, the temporal overestimation was greater when the
      expectation for the forthcoming threatening stimulus was longer. This temporal
      overestimation is explained in terms of a speeding-up of the neural timing system
      in response to the increase in the arousal level produced by the expectation of a
      threatening stimulus.

PMID- 21171763
TI  - The effect of embodied emotive states on cognitive categorization.
AB  - Research has uncovered that positive affect broadens cognitive categorization.
      The motivational dimensional model, however, posits that positive affect is not a
      unitary construct with only one cognitive consequence. Instead, this model puts
      forth that there are different positive affects varying in approach motivational
      intensity. According to this model, only positive affects lower in motivational
      intensity should broaden cognitive processes, whereas positive affects higher in
      motivational intensity should narrow cognitive processes. Consistent with these
      predictions, high approach positive affect has been shown to narrow attention,
      whereas low approach positive affect has been shown to broaden it (Gable & Harmon
      Jones, 2008). High approach positive affect, therefore, might narrow
      categorization. Two experiments investigated this possibility by having
      participants respond to cognitive categorization tasks in 3 body postures
      designed to elicit different levels of approach motivation: reclining backward,
      which should evoke low approach motivation; sitting upright, which should evoke
      moderate approach motivation; and leaning forward, which should evoke high
      approach motivation. Participants smiled while in each posture in order to
      experience positive affect. Experiment 1 provided initial support for the idea
      that high approach positive affect narrows categorization and low approach
      positive affect broadens categorization. Experiment 2 replicated these findings
      with improved smiling instructions. These results extend previous work by showing
      that the motivational model's predictions hold for basic attentional processes as
      well as higher level cognitive processes such as categorization.

PMID- 21171762
TI  - The ability to regulate emotion is associated with greater well-being, income,
      and socioeconomic status.
AB  - Are people who are best able to implement strategies to regulate their emotional
      expressive behavior happier and more successful than their counterparts? Although
      past research has examined individual variation in knowledge of the most
      effective emotion regulation strategies, little is known about how individual
      differences in the ability to actually implement these strategies, as assessed
      objectively in the laboratory, are associated with external criteria. In two
      studies, we examined how individual variation in the ability to modify emotional
      expressive behavior in response to evocative stimuli is related to well-being and
      financial success. Study 1 showed that individuals who can best suppress their
      emotional reaction to an acoustic startle are happiest with their lives. Study 2
      showed that individuals who can best amplify their emotional reaction to a
      disgust-eliciting movie are happiest with their lives and have the highest
      disposable income and socioeconomic status. Thus, being able to implement emotion
      regulation strategies in the laboratory is closely linked to well-being and
      financial success.

PMID- 21171764
TI  - When observing gaze shifts of others enhances object desirability.
AB  - The present research explored when observing gaze shifts of another person,
      involving both the observer and a specific object, enhances desirability of the
      gazed-at object. Specifically, we offer an initial attempt to test the idea that
      a three-step sequence consisting of direct gaze at the observer, followed by
      object-directed gaze and then by direct gaze at the observer, cues the
      desirability of an object to the observer and hence increases the perceived
      desirability of the gazed-at object. We examined this hypothesis in three
      experiments by manipulating eye-gaze shifts and including a no-gaze control
      condition. In line with our prediction, results showed that the dynamic sequence
      of gaze shifts indeed increases perceived object desirability. These findings
      provide new evidence that a sequence of gaze behavior involving the observer and
      an object plays an important role in influencing affective evaluation of objects.

PMID- 21171766
TI  - Physical aggression in unmarried relationships: the roles of commitment and
      constraints.
AB  - Using commitment theory, the present study explored longitudinal associations
      between physical aggression and various aspects of commitment and relationship
      stability. Participants (N = 1,278) were unmarried adults between the ages of 18
      and 35 who were in a heterosexual romantic relationship at the time of the
      initial assessment. Of these, 51.6% reported never experiencing physical
      aggression in their current relationship, 12.8% reported experiencing physical
      aggression in the past, but not in the last year, and 35.6% reported experiencing
      physical aggression in the last year. As hypothesized, those who had experienced
      aggression in the last year were more likely to have broken up 1 year later. They
      also generally reported lower levels of dedication and higher levels of
      constraint commitment compared with those with no history of physical aggression.
      Among those who had experienced aggression in the last year, constraints and
      other commitment-related variables explained more about who broke up over time
      than did relationship adjustment alone, indicating the importance of measuring
      commitment constructs in future research about which aggressive couples are most
      likely to end their relationships. Clinical implications of these results are
      discussed, particularly in regard to preventive relationship education programs.

PMID- 21171765
TI  - Sleeping with one eye open: marital abuse as an antecedent of poor sleep.
AB  - In a diverse community sample of 241 married couples, we examined received
      psychological abuse (PA) as a longitudinal predictor of men's and women's sleep.
      Participants reported on marital functioning and mental health during three
      assessments (T1, T2, T3) and sleep problems during two assessments (T2, T3), with
      1-year lags between waves. Growth curve analyses revealed that for both spouses,
      higher initial levels of PA and increases in PA over time predicted greater sleep
      disturbances at T3. For husbands and wives, anxiety and depression mediated some
      of the associations between PA and sleep problems. For wives, moderation effects
      highlighted the importance of violence, anxiety, and depression in exacerbating
      sleep problems associated with PA. Results build on and contribute significantly
      to the scant literature implicating the importance of the marital relationship
      for sleep and suggest that simultaneous consideration of intrapersonal and
      interpersonal variables is critical when explicating sleep disruptions.

PMID- 21171767
TI  - Intergenerational transmission of relationship aggression: a prospective
      longitudinal study.
AB  - The present study examined whether physical and verbal aggression in the family
      of origin were associated with similar patterns of aggression in young adult
      couples. Hypotheses were tested using a sample of 213 focal individuals who were
      followed from adolescence to adulthood. Results suggested that aggression in the
      family when focal participants were adolescents predicted aggression with
      romantic partners when participants were adults. The association between
      interparental aggression and later aggression in adult romantic unions was
      partially mediated through parents' aggression to focal participants when they
      were adolescents. Both physical and verbal aggression revealed the same pattern
      of findings. All together, these findings are consistent with a developmental
      interactional perspective (Capaldi & Gorman-Smith, 2003) concerning the
      developmental origins of aggression in intimate relationships.

PMID- 21171768
TI  - Links between sisters' sexual and dating victimization: the roles of neighborhood
      crime and parental controls.
AB  - This study examined the extent to which a sister's prior sexual and dating
      victimization is a risk factor for young women being similarly victimized and the
      possible factors underlying a co-occurrence. The sample involved 122 young adult
      Latina or African American sister pairs (244 women; ages 16-25) who resided in
      low-income, urban neighborhoods. Results indicated that women whose sisters had
      been victimized had increased risk of victimization even after controlling for
      neighborhood crime, parental controls, age and race-ethnicity (odds ratios were
      4.0 for unwanted touching, 6.2 for a forced sex act, and 16.7 for dating
      violence). In high-crime neighborhoods, the presence of two adult parent figures
      in the home was associated with women's reduced likelihood of unwanted touching,
      and mothers' high monitoring during adolescence was associated with women's lower
      risk of dating aggression. Survival analysis results showed that the risk period
      of a second sister being victimized lasts between 7 and 10 years after a first
      sister's victimization. The prevention implications of study findings are
      discussed.

PMID- 21171769
TI  - Family dynamics across pregnant Latina adolescents' transition to parenthood.
AB  - Growth curve models were conducted on assessments of family functioning at four
      time points from the third-trimester of pregnancy through the first year
      postpartum for 96 Latino families in which an adolescent daughter was pregnant.
      Results indicated significant family-level change following an adolescent's
      childbearing, though there were notable differences between family members in
      their perceptions of family functioning. Family conflict, as perceived by
      parenting teens, increased in the latter half of the first year after an initial
      decline, and family companionship (as rated by mothers and siblings) decreased.
      Parenting adolescents and siblings perceived significant increases in family
      cohesion, whereas mothers perceived a significant decline. Unplanned pregnancies,
      family financial hardship, and expected stress predicted unfavorable family
      functioning at 1 year. Contrary to expectations, adolescents' greater prenatal
      efforts to prepare for parenting predicted subsequent family conflict and
      declines in family cohesion (particularly as rated by mothers). Family members'
      acculturation level and attitudes of familism, gender roles, and the status
      attained by parenthood also had predictive effects. Implications of study
      findings for family adjustment following an adolescent's childbearing are
      discussed.

PMID- 21171771
TI  - How can parents make a difference? Longitudinal associations with adolescent
      sexual behavior.
AB  - Parents have the potential to protect against adolescent sexual risk, including
      early sexual behavior, inconsistent condom use, and outcomes such as pregnancy
      and sexually transmitted infections (STIs). Identification of the specific
      parenting dimensions associated with sexual risk in adolescence and young
      adulthood is necessary to inform and focus prevention efforts. The current study
      examined the relation of proximal (e.g., discussions of sexual costs) and distal
      (e.g., parental involvement, relationship quality) parenting variables with
      concurrent and longitudinal adolescent sexual behavior. The National Longitudinal
      Study of Adolescent Health (Add Health) provided a nationally representative
      sample with information about the family using adolescent and parent informants.
      Longitudinal information about sexual risk included adolescent condom use and
      adolescent sexual initiation, as well as young adult unintended pregnancy,
      reports of STIs, and biological assay results for three STIs. Higher parent
      adolescent relationship quality was associated with lower levels of adolescent
      unprotected intercourse and intercourse initiation. Better relationship quality
      was also associated with lower levels of young adult STIs, even when accounting
      for prior sexual activity. Unexpectedly, more parent reports of communication
      regarding the risks associated with sexual activity were negatively associated
      with condom use and greater likelihood of sexual initiation. These results
      demonstrate that parents play an important role, both positive and negative, in
      sexual behavior, which extends to young adulthood, and underscores the value of
      family interventions in sexual risk prevention.

PMID- 21171770
TI  - Adolescent personality as a prospective predictor of parenting: an interactionist
      perspective.
AB  - This study examined personality during adolescence as a predictor of later
      parenting of toddler-aged offspring. On the basis of empirical research on the
      timing of parenthood and the interactionist model (Conger & Donnellan, 2007), we
      examined age at parenthood and family socioeconomic status (SES) as mediators of
      the relation between personality and parenting. Participants were 228 emerging
      adults from an ongoing longitudinal study of the transition to adulthood. Later
      entry into parenthood and higher SES accounted for the association between
      personality characteristics and lower levels of harsh parenting and higher levels
      of positive parenting. Consistent with the interactionist model, both personality
      characteristics and SES-linked variables were related to interpersonal processes
      in families. The findings suggest that promoting adaptive personality traits
      during childhood and adolescence may help delay early entry into parenthood,
      promote higher SES, and, indirectly, foster more positive parenting of young
      children.

PMID- 21171772
TI  - Does college-based relationship education decrease extradyadic involvement in
      relationships?
AB  - We used latent growth curve modeling to examine the effectiveness of a
      relationship education intervention (Relationship U, or RU) on rates of
      extradyadic involvement in a sample of 380 college students in committed romantic
      relationships. RU is designed to be integrated into existing college courses; it
      educates students about partner selection, making healthy relationship
      transitions, communication skills, and the potentially negative consequences of
      cheating in romantic relationships and how to prevent its occurrence.
      Participants who received the intervention reported trajectories of less
      extradyadic involvement over time relative to control participants. Being female
      was not associated with less extradyadic involvement at baseline, but it did
      predict less extradyadic involvement over time across both intervention and
      control conditions. Implications for dissemination of relationship education are
      discussed.

PMID- 21171774
TI  - Perceived maternal parenting as a mediator of the intergenerational similarity of
      dependency and self-criticism: a study with Arab Jordanian adolescents and their
      mothers.
AB  - This study investigated the intergenerational similarity of personality
      vulnerability to depression as conceptualized by Blatt (1974) in a sample of Arab
      Jordanian mothers and their adolescents. Perceived maternal parenting was
      examined as a mediator of the intergenerational similarity of two personality
      vulnerabilities; that is, dependency and self-criticism. Both mothers and
      adolescents (N = 298 families) completed the Depressive Experiences Questionnaire
      (DEQ) to tap into personality vulnerability and adolescents additionally provided
      ratings of maternal parenting (support and psychological control) and depressive
      symptoms. Findings showed significant and specific associations between mothers'
      and adolescents' dependency and self-criticism. Perceived maternal parenting was
      found to mediate this intergenerational similarity at least partially. This study
      is among the first to test developmental hypotheses derived from Blatt's theory
      in a non-Western sample. Findings show striking similarity with data obtained in
      the West and, as such, contribute to the cross-cultural generalization of the
      theory.

PMID- 21171773
TI  - Structural Ecosystems Therapy for recovering HIV-positive women: child, mother,
      and parenting outcomes.
AB  - This study presents results of a subgroup analysis from a randomized trial to
      examine whether Structural Ecosystems Therapy (SET), a family intervention
      intended to improve medication adherence and reduce drug relapse of HIV
      seropositive (HIV+) women recovering from drug abuse, provided benefits for
      families with children. Data from 42 children and 25 mothers were analyzed at
      baseline, and 4, 8, and 12 months post-baseline. Results of longitudinal
      Generalized Estimating Equations analyses suggested that SET was more efficacious
      than the Health Group (HG) control condition in decreasing children's
      internalizing and externalizing problems and reducing mothers' psychological
      distress and drug relapse. Children in SET reported improvements in positive
      parenting as compared to the children in HG, but there were no differences in
      mother-reported positive parenting, or parental involvement as reported by either
      the children or mothers. These findings suggest that family interventions such as
      SET may be beneficial for mothers and children. An adaptation of SET specifically
      for families with children could further enhance benefits and improve
      acceptability and cost-effectiveness.

PMID- 21171775
TI  - Compatibility or restraint? The effects of sexual timing on marriage
      relationships.
AB  - Very little is known about the influence of sexual timing on relationship
      outcomes. Is it better to test sexual compatibility as early as possible or show
      sexual restraint so that other areas of the relationship can develop? In this
      study, we explore this question with a sample of 2035 married individuals by
      examining how soon they became sexually involved as a couple and how this timing
      is related to their current sexual quality, relationship communication, and
      relationship satisfaction and perceived stability. Both structural equation and
      group comparison analyses demonstrated that sexual restraint was associated with
      better relationship outcomes, even when controlling for education, the number of
      sexual partners, religiosity, and relationship length.

PMID- 21171777
TI  - Food choices of 4 to 6-year-old overweight and nonoverweight children while role
      playing as adults.
AB  - The following study compared the food choices made by overweight and non
      overweight preschoolers while role-playing a mother who bought food for a family,
      and examined the influence of maternal restriction on food choice. After
      screening 619 children for height and weight, 56 overweight children (equal sex
      distribution, ages 4-6) and 56 non-overweight children (matched on age, sex,
      demographics) were selected to participate. Children's purchases of low and high
      caloric snacks, drinks, and dinner products in a miniature supermarket were
      recorded. Mother and child-reported maternal restriction were assessed using the
      Child Feeding Questionnaire (CFQ) and the Kid's CFQ. Compared to non-overweight
      children, overweight children choose more high-calorie foods when role-playing a
      mother. Maternal restriction did not differ between overweight and non-overweight
      children. Both children's and mothers' reported maternal restriction were
      unrelated to food choices and there were no significant interactions between
      restriction and weight status on food choices. In conclusion, while parental
      restriction seems to be unrelated to children's food choices, family food
      patterns might have great impact already at young ages.

PMID- 21171776
TI  - Nonexpert ratings of family and parent-child interaction.
AB  - Observational methods benefit the study of family process, but many expert rating
      systems are costly and time-consuming. This study examined the utility of using
      small groups of eight to ten nonexperts to rate family conflict and maternal
      sensitivity. Videotaped triadic interactions of 39 families were drawn from
      Lindahl (1998), and 22 mother-toddler free-play interactions were drawn from
      Baker, Messinger, Lyons, and Grantz (2010). Sixty undergraduates rated
      interactions from these samples in real time using computer-assisted technology.
      Nonexpert ratings of family conflict were reliable, demonstrated high concordance
      with expert ratings, and replicated a key finding from Lindahl (1998). Nonexpert
      ratings of maternal sensitivity replicated a relevant finding from Baker,
      Messinger et al. (2010). Concordance was lower for maternal sensitivity, however,
      because of the tendency of nonexperts to overattend to sensitive structuring
      compared with emotional supportiveness. A second study indicated that as few as
      six nonexperts could effectively rate maternal sensitive structuring, but that
      nonexperts were unable to accurately rate emotional supportiveness. Implications
      for research methods and for our understanding of these important family
      constructs are discussed.

PMID- 21171778
TI  - Italian international adoptees at home and at school: a multi-informant
      assessment of behavioral problems.
AB  - The aim of this study was to compare the reports of emotional and behavioral
      problems of adopted children on the part of mothers, fathers, and teachers, and
      to examine the agreement in the reports among the three informants. The approach
      employed was multi-informant, with a three-point sample composed of 75 Italian
      couples (all parents of international adoptees between 7 and 11 years of age) and
      one of the child's teachers. Parents reported higher levels of problems in their
      adopted children than teachers did. Moreover, the agreement between mother and
      father was higher than that between one parent and the teacher. The percentage of
      cases in which all three informants agreed on the classification of the child as
      being part of the clinical group turned out to be considerably lower than when
      only one informant was concerned.

PMID- 21171779
TI  - Forgiveness increases the likelihood of subsequent partner transgressions in
      marriage.
AB  - Despite a growing literature on the positive implications of forgiveness and
      recent efforts to promote forgiveness in marriage, there is reason to believe
      forgiveness could have yet-unknown negative implications. In particular,
      forgiveness may increase the likelihood that offenders will offend again by
      removing unwanted outcomes for those offenders (e.g., criticism, guilt,
      loneliness) that would otherwise discourage them from reoffending. Consistent
      with this possibility, the current 7-day-diary study revealed that newlywed
      spouses were more likely to report that their partners had engaged in a negative
      behavior on days after they had forgiven those partners for a negative behavior
      than on days after they had not forgiven those partners for a negative behavior.
      Interpersonal theories and interventions designed to treat and prevent
      relationship distress may benefit by acknowledging this potential cost of
      forgiveness.

PMID- 21171780
TI  - Relationship satisfaction instability and depression.
AB  - In this study, we explored whether the degree of temporal instability in
      relationship satisfaction might add to our understanding of the well-documented
      association between relationship quality and depression. We hypothesized that
      greater relationship satisfaction instability would be associated with higher
      depressive symptoms, controlling for mean satisfaction levels. We conducted 12
      weekly assessments of relationship satisfaction and depressive symptoms in a
      sample of 131 cohabiting and married women, and used intraindividual standard
      deviations of scores over the 12 weeks as an index of instability. Results
      indicated that, as hypothesized, relationship satisfaction instability predicted
      variance in depressive symptoms beyond that predicted by mean satisfaction; women
      whose weekly relationship satisfaction fluctuated more widely tended to have
      higher depressive symptoms. In comparison, temporal instability in depressive
      symptoms did not predict variance in relationship satisfaction beyond that
      predicted by mean depressive symptoms. Prospective analyses tentatively suggested
      that satisfaction instability may precede rather than follow elevated depressive
      symptoms. Results suggest the utility of assessing relationship satisfaction
      instability in future studies exploring links between marital quality and
      depression.

PMID- 21171782
TI  - Orthogonal higher order structure and confirmatory factor analysis of the French
      Wechsler Adult Intelligence Scale (WAIS-III).
AB  - According to the most widely accepted Cattell-Horn-Carroll (CHC) model of
      intelligence measurement, each subtest score of the Wechsler Intelligence Scale
      for Adults (3rd ed.; WAIS-III) should reflect both 1st- and 2nd-order factors
      (i.e., 4 or 5 broad abilities and 1 general factor). To disentangle the
      contribution of each factor, we applied a Schmid-Leiman orthogonalization
      transformation (SLT) to the standardization data published in the French
      technical manual for the WAIS-III. Results showed that the general factor
      accounted for 63% of the common variance and that the specific contributions of
      the 1st-order factors were weak (4.7%-15.9%). We also addressed this issue by
      using confirmatory factor analysis. Results indicated that the bifactor model
      (with 1st-order group and general factors) better fit the data than did the
      traditional higher order structure. Models based on the CHC framework were also
      tested. Results indicated that a higher order CHC model showed a better fit than
      did the classical 4-factor model; however, the WAIS bifactor structure was the
      most adequate. We recommend that users do not discount the Full Scale IQ when
      interpreting the index scores of the WAIS-III because the general factor accounts
      for the bulk of the common variance in the French WAIS-III. The 4 index scores
      cannot be considered to reflect only broad ability because they include a strong
      contribution of the general factor.

PMID- 21171781
TI  - Cognitive consequences of expressive regulation in older adults.
AB  - Previous research has suggested that older and young adults are equally able to
      regulate their outward expressions of emotion and that the regulation of
      emotional expression in younger adults results in decreased memory for the
      emotional stimulus. In the current study, we examined whether older adults show
      this same memory effect. Older and young adults viewed positive and negative
      emotional pictures under instructions to view the pictures naturally, enhance
      their facial expressions, or suppress their facial expressions. Older and young
      adults showed equivalent outward regulation of expression, but suppressing their
      emotional expressions led to reduced memory for emotional stimuli only in the
      young adults. The results suggest that older and young adults are achieving
      control of their expressions through different mechanisms or strategies.

PMID- 21171783
TI  - Delineating the construct network of the Personnel Reaction Blank: associations
      with externalizing tendencies and normal personality.
AB  - Integrity testing has long been utilized in personnel selection to screen for
      tendencies toward counterproductive workplace behaviors. The construct of
      externalizing from the psychopathology literature represents a coherent spectrum
      marked by disinhibitory traits and behaviors. The present study drew on a sample
      of male and female undergraduates to examine the construct network of the
      Personnel Reaction Blank (PRB; H. G. Gough, R. D. Arvey, & P. Bradley, 2004), a
      measure of integrity, in relation to externalizing as well as normal-range
      personality constructs assessed by the Multidimensional Personality Questionnaire
      (MPQ; A. Tellegen & N. G. Waller, 2008). Results revealed moderate to strong
      associations between several PRB scales and externalizing, which were largely
      accounted for by MPQ traits subsumed by Negative Emotionality and Constraint.
      After accounting for MPQ traits in the prediction of externalizing, a modest
      predictive increment was achieved when adding the PRB scales, particularly
      biographical indicators from the Prosocial Background subscale. The findings
      highlight externalizing as a focal criterion for scale development in the
      integrity testing literature and help delineate the construct network of the PRB
      within the domains of personality and psychopathology.

PMID- 21171784
TI  - Assessing the basic traits associated with psychopathy: development and
      validation of the Elemental Psychopathy Assessment.
AB  - A new self-report assessment of the basic traits of psychopathy was developed
      with a general trait model of personality (five-factor model [FFM]) as a
      framework. Scales were written to assess maladaptive variants of the 18 FFM
      traits that are robustly related to psychopathy across a variety of perspectives
      including empirical correlations, expert ratings, and translations of extant
      assessments. Across 3 independent undergraduate samples (N = 210-354), the
      Elemental Psychopathy Assessment (EPA) scales proved to be internally consistent
      and unidimensional, and were strongly related to the original FFM scales from
      which they were derived (mean convergent r = .66). The EPA scales also
      demonstrated substantial incremental validity in the prediction of existing
      psychopathy measures over their FFM counterparts. When summed to form a
      psychopathy total score, the EPA was substantially correlated with 3 commonly
      used psychopathy measures (mean r = .81). Finally, in a small male forensic
      sample (N = 70), the EPA was significantly correlated with scores on a widely
      used self-report psychopathy measure, disciplinary infractions, alcohol use, and
      antisocial behavior. The EPA provides an opportunity to examine psychopathy and
      its nomological network through smaller, more basic units of personality rather
      than by scales or factors that blend these elements.

PMID- 21171785
TI  - Comparing posttraumatic stress disorder's symptom structure between deployed and
      nondeployed veterans.
AB  - We tested two empirically validated 4-factor models of posttraumatic stress
      disorder (PTSD) symptoms using the PTSD Checklist: King, Leskin, King, and
      Weathers' (1998) model including reexperiencing, avoidance, emotional numbing,
      and hyperarousal factors, and Simms, Watson, and Doebbeling's (2002) model
      including reexperiencing, avoidance, dysphoria, and hyperarousal. Our aim was to
      determine which fit better in two groups of military veterans: peacekeepers
      previously deployed to a war zone (deployed group) and those trained for
      peacekeeping operations who were not deployed (nondeployed group). We compared
      the groups using multigroup confirmatory factor analysis. Adequate model fit was
      demonstrated among the nondeployed group, with no significant difference between
      King et al.'s (1998) model (separating avoidance and numbing) and Simms et al.'s
      (2002) similar model involving a dysphoria factor. A better fitting factor
      structure consistent with Simms et al.'s (2002) model was found in the deployed
      group. Comprehensive measurement invariance testing demonstrated significant
      differences between the deployed and nondeployed groups on all structural
      parameters, except observed variable intercepts (thus indicating similarities
      only in PTSD item severity). These findings add to researchers' understanding of
      PTSD's factor structure, given the revision of PTSD that will appear in the
      forthcoming 5th edition of the Diagnostic and Statistical Manual of Mental
      Disorders (American Psychiatric Association, 2010)--namely, that the factor
      structure may be quite different between groups with and without exposure to
      major traumatic events.

PMID- 21171786
TI  - Caution: fragile! Regulating the interpersonal security of chronically insecure
      partners.
AB  - The authors present and test a model of interpersonal insecurity compensation.
      According to this model, perceivers detect targets' chronic insecurities about
      interpersonal acceptance, become vigilant about upsetting targets, and respond
      with affective exaggeration, which involves cautiously inflating positive
      thoughts and feelings about targets and concealing negative sentiments. Results
      of 3 studies support this model across a variety of relationship types.
      Perceivers who detected targets' chronic insecurities concealed negative
      sentiments when they believed their sentiments would be observed by targets
      (Study 1), converged with other perceivers in their self-reported affective
      exaggeration to insecure targets (Study 2), and reported vigilance about
      upsetting targets, which predicted perceivers' enhanced cognitive processing of
      targets' daily insecurity and intensified their tendencies to exaggerate
      affections in response to that insecurity (Study 3). Perceivers' affective
      exaggeration appeared to enhance chronically insecure targets' perceptions of
      being valued by perceivers, but it also predicted perceivers' reduced
      relationship satisfaction (Studies 2 and 3). Results underscore the active, but
      perhaps dissatisfying, regulation of relationships with chronically insecure
      relationship partners.

PMID- 21171788
TI  - Affective influences on self-disclosure: mood effects on the intimacy and
      reciprocity of disclosing personal information.
AB  - How does mood influence people's willingness to disclose intimate information
      about themselves? Based on recent affect-cognition theories and research on
      interpersonal behavior, 3 experiments predicted and found that people in a
      positive mood disclosed more intimate, more varied, and more abstract information
      about themselves. In contrast, people in a negative mood were more attentive to
      the behavior of others and reciprocated self-disclosure from their partners more
      accurately. This effect was obtained in hypothetical situations (Experiments 1
      and 2) and in realistic computer-mediated interactions as well (Experiment 3).
      Experiments 2 and 3 confirmed that mood effects on self-disclosure were mediated
      by information processing style. The role of affect in information processing and
      relationship behaviors in particular is discussed, and the implications of these
      findings for everyday interaction strategies and for contemporary affect
      cognition theorizing are considered.

PMID- 21171787
TI  - Age differences in personality traits from 10 to 65: Big Five domains and facets
      in a large cross-sectional sample.
AB  - Hypotheses about mean-level age differences in the Big Five personality domains,
      as well as 10 more specific facet traits within those domains, were tested in a
      very large cross-sectional sample (N = 1,267,218) of children, adolescents, and
      adults (ages 10-65) assessed over the World Wide Web. The results supported
      several conclusions. First, late childhood and adolescence were key periods.
      Across these years, age trends for some traits (a) were especially pronounced,
      (b) were in a direction different from the corresponding adult trends, or (c)
      first indicated the presence of gender differences. Second, there were some
      negative trends in psychosocial maturity from late childhood into adolescence,
      whereas adult trends were overwhelmingly in the direction of greater maturity and
      adjustment. Third, the related but distinguishable facet traits within each broad
      Big Five domain often showed distinct age trends, highlighting the importance of
      facet-level research for understanding life span age differences in personality.

PMID- 21171789
TI  - Perceived proposer personality characteristics and gender differences in
      acceptance of casual sex offers.
AB  - In a highly influential paper, Clark and Hatfield (1989) demonstrated that,
      whereas men were quite likely to accept a casual sexual offer from a confederate
      research assistant, women never did so. The current research provides a more in
      depth explanation of gender differences in acceptance of casual sex offers via 4
      (quasi-) experiments. First, using a person-perception paradigm, I assessed
      people's impressions of women and men who proposed a casual sexual encounter in
      the same manner that confederates in Clark and Hatfield did. Women and men agreed
      that female proposers were more intelligent, successful, and sexually skilled
      than men who made the same proposals. Second, I demonstrated that the large
      gender differences from the original Clark and Hatfield study could be eliminated
      by asking participants to imagine proposals from (attractive and unattractive)
      famous individuals, friends, and same-gender individuals. Next, I assessed
      factors associated with likelihood of agreeing to the casual sex proposal. The
      extent to which women and men believed that the proposer would be sexually
      skilled predicted how likely they would be to engage in casual sex with this
      individual. Finally, I examined these factors in the context of actual encounters
      from the participants' previous experiences, and the results were replicated in
      this context. Overall findings suggest that the large gender differences Clark
      and Hatfield observed in acceptance of the casual sex offer may have more to do
      with perceived personality characteristics of the female versus male proposers
      than with gender differences among Clark and Hatfield's participants and that
      sexual pleasure figures largely in women's and men's decision making about casual
      sex.

PMID- 21171790
TI  - Bodies obliged and unbound: differentiated response tendencies for injunctive and
      descriptive social norms.
AB  - The authors suggest that injunctive and descriptive social norms engage different
      psychological response tendencies when made selectively salient. On the basis of
      suggestions derived from the focus theory of normative conduct and from
      consideration of the norms' functions in social life, the authors hypothesized
      that the 2 norms would be cognitively associated with different goals, would lead
      individuals to focus on different aspects of self, and would stimulate different
      levels of conflict over conformity decisions. Additionally, a unique role for
      effortful self-regulation was hypothesized for each type of norm-used as a means
      to resist conformity to descriptive norms but as a means to facilitate conformity
      for injunctive norms. Four experiments supported these hypotheses. Experiment 1
      demonstrated differences in the norms' associations to the goals of making
      accurate/efficient decisions and gaining/maintaining social approval. Experiment
      2 provided evidence that injunctive norms lead to a more interpersonally oriented
      form of self-awareness and to a greater feeling of conflict about conformity
      decisions than descriptive norms. In the final 2 experiments, conducted in the
      lab (Experiment 3) and in a naturalistic environment (Experiment 4), self
      regulatory depletion decreased conformity to an injunctive norm (Experiments 3
      and 4) and increased conformity to a descriptive norm (Experiment 4)-even though
      the norms advocated identical behaviors. By illustrating differentiated response
      tendencies for each type of social norm, this research provides new and
      converging support for the focus theory of normative conduct.

PMID- 21171791
TI  - Investing in our future: unrealized opportunities for funding graduate psychology
      training.
AB  - PURPOSE: Changes in the health care environment have brought challenges and
      opportunities to the field of psychology. Practitioners have been successful in
      modifying service models to absorb losses of financial support for behavioral
      health care, due to managed care and public policy changes, while simultaneously
      managing the growing need for these services. However, in this reactive mode of
      responding to evolutions in the health care system, the field of psychology has
      at times lost sight of the long-term vision required to promote psychology's
      inclusion in the health care system of the future. In particular, a focus on
      training psychologists and ensuring the availability of funding to support these
      activities must be a priority in planning for the future. This article provides
      an overview of federal programs that currently offer funding for psychology
      training, as well as other opportunities for federal funding that have been
      unrealized. Details regarding advocacy efforts that were required to secure
      available sources of funding are given, followed by consideration of strategies
      for taking advantage of existing resources and prioritizing advocacy for
      additional funding. CONCLUSION: Funding for psychology training provides an
      avenue for increasing the number of well-trained psychologists who can serve
      patients' mental and behavioral health needs and thereby improve health outcomes.
      Moreover, capitalizing on available funding opportunities for psychology training
      and promoting efforts to expand these opportunities will help ensure that the
      field of psychology is positioned to remain an important contributor to the
      health care system of the future.

PMID- 21171792
TI  - Inpatient rehabilitation diabetes consult service: a rehabilitation psychology
      approach to assessment and intervention.
AB  - PROBLEM: Diabetes clinical practice recommendations call for assessment and
      intervention on diabetes self-management during inpatient hospitalization.
      Although diabetes is prevalent in inpatient rehabilitation settings, diabetes
      self-management has not traditionally been a focus of inpatient rehabilitation
      psychology care. This is because diabetes is often a secondary diagnosis when an
      individual is admitted to rehabilitation for an acute event. OBJECTIVES: The
      authors provide a rationale for a role for rehabilitation psychologists in
      assessing and intervening on the psychosocial, behavioral, and functional self
      management needs of individuals with diabetes within the rehabilitation setting.
      The development of a rehabilitation psychology Inpatient Rehabilitation Diabetes
      Consultation Service is described. Theoretical and empirical bases for
      compilation of the assessment and intervention materials are provided. Format and
      implementation of the service on a university-affiliated inpatient rehabilitation
      unit is described, with special consideration given to professional issues faced
      by rehabilitation psychologists and teams. RESULTS: A flexible consultation model
      was implemented using a guided diabetes psychosocial assessment with brief
      educational handouts addressing selected key topics (i.e., hyperglycemia,
      hypoglycemia, blood sugar monitoring, nutrition, physical activity, medication,
      and, A1C and average blood sugar). The consultation service was feasible and well
      accepted by treated individuals and the rehabilitation team. CONCLUSIONS:
      Rehabilitation psychologists are uniquely positioned to address the functional,
      psychosocial, and behavioral needs of individuals with diabetes. With further
      research to assess clinical outcomes, this approach may further address practice
      recommendations for inpatient diabetes care. Moreover, such a diabetes
      consultation model may be useful on an outpatient rehabilitation basis as well.

PMID- 21171793
TI  - The impact of family, peer, and school contexts on depressive symptoms in
      adolescents with spina bifida.
AB  - OBJECTIVE: Based on social ecological theory, this study examined the joint
      relations among adolescents' family, peer, and school contexts and depressive
      symptoms in youth with spina bifida using cumulative, protective, and specific
      effects models. METHOD: Sixty families of adolescents with spina bifida and 65
      comparison families reported on adolescents' positive experiences within these
      contexts and on depressive symptoms when youth were 14-15 and 16-17 years old.
      RESULTS: Adolescents with spina bifida had fewer total positive contexts and less
      positive experience within peer and school contexts, as compared to typically
      developing adolescents. Greater total number of positive contexts and higher
      levels of positive experiences within family and school contexts were associated
      with fewer depressive symptoms for both groups; peer positive experiences were
      related to lower depressive symptoms for typically developing adolescents only.
      CONCLUSION: Adolescents with spina bifida have fewer positive contexts, which may
      place them at risk for higher levels of depressive symptoms.

PMID- 21171794
TI  - Does individualism help explain differences in employers' stigmatizing attitudes
      toward disability across Chinese and American cities?
AB  - PURPOSE: Stigmatizing attitudes toward people with disabilities can jeopardize
      such individuals' well-being and recovery through denial of employment and
      community isolation. By shaping social norms that define group membership, the
      construct of individualism may partially explain differences in stigmatizing
      attitudes across cultures. Further, widespread globalization has brought
      intensely individualistic social practices to certain segments of non-Western
      cultures. This paper examines whether the construct of individualism can help to
      explain cross-cultural differences in stigmatizing attitudes observed between
      American and Chinese employers. DESIGN: Employers (N = 879) from Beijing, Hong
      Kong, and Chicago provided information on their attitudes toward hiring people
      with disabilities, and path analyses were conducted to examine potential
      mediating relationships. RESULTS: Path analyses indicated that vertical
      individualism, along with perceived responsibility for acquiring a condition,
      partially mediated the relationship between culture and employers' negative
      attitudes about job candidates with disabilities. CONCLUSION: These results
      suggested that greater espousal of competitive and individualist values may drive
      stigmatizing attitudes across cultures.

PMID- 21171795
TI  - Perceived stigmatization and social comfort: validating the constructs and their
      measurement among pediatric burn survivors.
AB  - OBJECTIVE: The current study implemented a four-step process to evaluate the
      measurement properties of the Perceived Stigmatization Questionnaire (PSQ) and
      the Social Comfort Questionnaire (SCQ) among long-term pediatric burn survivors.
      METHODS: First, a series of confirmatory factor analyses (CFAs) compared the
      hypothesized four-factor model--3 perceived stigmatization factors (absence of
      friendly behavior, confused and staring behavior, and hostile behavior)--and one
      social comfort factor to three other models. Second, we tested the measurement
      invariance of the instruments between pediatric and adult burn survivor samples.
      Third, possible differences in structural parameters across groups were tested.
      Fourth, we tested whether the three perceived stigmatization factors and the
      social comfort factor loaded on one second-order factor. Participants included
      369 pediatric and 347 adult burn survivors. RESULTS: The four-factor model was
      superior to the comparison models. The PSQ and SCQ demonstrated measurement
      invariance. Factor variance, factor covariance, and the latent means of the PSQ
      did not vary across groups. The adult group had a significantly lower latent mean
      on the SCQ than the pediatric group. The three factors of the PSQ and the one
      factor SCQ loaded on one second-order factor. CONCLUSION: The results of this
      study lend support to both the construct validity of perceived stigmatization and
      social comfort and the potential value of the PSQ and SCQ for studying the social
      experience of people with visible differences.

PMID- 21171796
TI  - Caregiver mental health and racial/ethnic disparities in stroke: implications for
      culturally sensitive interventions.
AB  - PURPOSE/OBJECTIVE: The purpose of this study was to create a set of culturally
      sensitive mental-health-intervention recommendations for the caregivers of
      Latino/Puerto-Rican, Black, and White individuals with stroke. The study examined
      whether the mental health of stroke caregivers and functioning of individuals
      with stroke differed according to race/ethnicity, changed differentially over
      time according to race/ethnicity, and showed relationships between the two sets
      of constructs that differed according to race/ethnicity. RESEARCH METHOD/DESIGN:
      Data on caregiver mental health and functioning of individuals with stroke were
      collected from 124 (n = 248) White, Black, and Latino/Puerto-Rican dyads at 1, 6,
      and 12 months post-hospital discharge. RESULTS: Out of the three racial/ethnic
      groups, Latino/Puerto-Rican individuals with stroke showed the lowest
      functioning, and their caregivers showed the poorest mental health, though the
      mental-health effects did not reach statistical significance. Consistent patterns
      which differed as a function of race/ethnicity emerged over time in the
      relationships between caregiver mental health and functioning of individuals with
      stroke. CONCLUSIONS/IMPLICATIONS: Critical knowledge may be lost regarding the
      connections between caregiver mental health and the functioning of individuals
      with stroke when researchers and clinicians look only across race/ethnicity as
      opposed to also within. A monolithic racial/ethnic approach to mental-health
      interventions for stroke rehabilitation is likely limited, and race/ethnicity may
      affect how caregiver mental health and functioning of individuals with stroke
      reciprocally influence each other.

PMID- 21171797
TI  - Exercise as stigma management for individuals with onset-controllable and onset
      uncontrollable spinal cord injury.
AB  - Studies have suggested that individuals with physical disabilities are often
      stigmatized and are perceived to possess less favorable physical and
      psychological characteristics than individuals without disability. PURPOSE: To
      investigate whether able-bodied adults' perceptions of people with different
      causes of spinal cord injury (SCI) are influenced by physical activity status
      information. METHOD AND PARTICIPANTS: Each participant (N = 198) read all five
      vignettes describing individuals with SCI who had varying levels of physical
      activity participation and cause of injury information (e.g., onset
      uncontrollable [hit by impaired driver] and onset-controllable [caused by
      impaired driving]). After reading each vignette, participants completed a 12-item
      Warmth and Competence Questionnaire to evaluate each target. One-way repeated
      measures multivariate analyses of variance were conducted to examine the within
      subjects differences. RESULTS: Physically active individuals with onset
      uncontrollable SCI were rated most favorably on warmth and competence. Physically
      active individuals with onset-controllable SCI also were rated more favorably on
      warmth and competence than physically inactive targets with onset-controllable
      SCI. CONCLUSION: A physically active lifestyle may be beneficial in managing the
      stigma experienced by individuals with both onset-controllable and onset
      uncontrollable SCI.

PMID- 21171799
TI  - Validity of a stage algorithm for physical activity in participants recruited
      from orthopedic and cardiac rehabilitation clinics.
AB  - OBJECTIVE: For stage-matched interventions, individuals must be classified with
      respect to their previous behaviors and in conjunction with their future
      intentions. A novel procedure for the assessment of stages in physical activity
      was developed. For this, individuals' activity and their regarding intentions
      were compared with recommended levels of activity. The aim was to examine the
      psychometric properties. DESIGN: In a cross-sectional study, stages were assessed
      in 366 study participants (84 in cardiac and 282 in orthopedic rehabilitation) in
      terms of their previous physical activity and their intention to perform
      recommended activity levels in the future. MAIN OUTCOME MEASURES: Stages of
      change were compared to self-reported behavior, intention, planning, self
      efficacy, risk perception, pros, cons, and social support. Misclassification,
      sensitivity, specificity, receiver operating characteristic (ROC) curves, non
      linear trends, and planned contrasts were computed. RESULTS: In comparison to
      previous studies, sensitivity (44%-99%) was high and specificity was similar or
      low (3%-88%), depending on the type of validation outcome selected. When using
      less demanding criteria (i.e., less intensive activity), measurement quality
      decreased, although not always significantly. Applying contrast analyses, more
      than half of the predicted stage differences were confirmed. No main differences
      between orthopedic and cardiac, ambulant and stationary rehabilitation appeared
      and no interactions were found. CONCLUSION: The stage algorithm proved to have
      acceptable measurement qualities in study participants recruited in both cardiac
      and orthopedic rehabilitation. Especially in detecting Intenders and Actors the
      stage algorithm performed well. Mechanisms of adopting and maintaining
      recommended activity levels seem to operate equally in both groups.

PMID- 21171798
TI  - Risk factors for stress in children after parental stroke.
AB  - OBJECTIVES: To assess risk factors for stress in children 3 years after parental
      stroke. PARTICIPANTS: Questionnaires were filled in by 44 children aged 7-18
      years, parents who suffered a stroke and healthy spouses from 29 families
      recruited in 9 participating rehabilitation centers across the Netherlands.
      METHOD: We measured patient functioning (cognitive disorders, communicative
      disorders and ADL dependency), parental depression and perceived quality of
      marital relationship at 4 assessments, from the start of rehabilitation until 3
      years post-stroke. Children assessed their stress level 3 years after parental
      stroke. RESULTS: Girls experienced more stress than boys. Spouses' depressive
      symptoms during the first year after stroke were positively correlated with
      stress in children. Patients' depressive symptoms 2 months post-rehabilitation (2
      months after discharge from the rehabilitation center), 1 year and 3 years post
      stroke were also positively correlated with stress in children. The perceived
      quality of marital relationship decreased over time and at 2 months post
      rehabilitation, it was related to stress in children. Stress was not related to
      patient gender and functioning. CONCLUSIONS: Early prediction of long-term stress
      in children after parental stroke may be most accurate on the basis of children's
      female gender and depressive symptoms of the patient.

PMID- 21171800
TI  - Compound caregiving: when lifelong caregivers undertake additional caregiving
      roles.
AB  - OBJECTIVE: Lifetime parental caregivers of adults with intellectual disabilities
      (ID) may also become caregivers to other family members. This study investigated
      caregiver experiences of compound caregiving (i.e. additional caregiving roles)
      and its association with caregiver quality of life. PARTICIPANTS: Ninety-one
      older caregivers living with their adult son/daughter with ID were interviewed.
      Mean age of the caregivers was 60 years and their sons'/daughters' mean age was
      29 years. MAIN OUTCOME MEASURES: Compound caregiving status, physical and mental
      health, life satisfaction, depressive symptomatology, and desire for alternative
      residential placement for their co-residing son/daughter. RESULTS: Thirty-four
      (37%) reported being current compound caregivers to an additional care recipient,
      predominantly a mother, father, or spouse. Caregivers averaged 39 hours per week
      fulfilling their primary caregiving tasks, an additional 12 hours per week on the
      compound caregiving role, and the median duration of compound caregiving was 3
      years. Compared with the non-compound caregivers, the compound caregivers had
      increased desire to place their son/daughter into residential care, though no
      group differences were apparent in life satisfaction, depressive symptomatology,
      physical health, or mental health. The most problematic issues reported by
      compound caregivers were having little personal time and a lack of adequate help
      from others. CONCLUSION: Compound caregiving was often experienced, and may
      galvanize these lifetime caregivers to start making future plans for their
      sons/daughters. Future research is warranted to refine more homogeneous groupings
      of compound caregivers, who may be at greater risk for adverse outcomes.

PMID- 21171802
TI  - Threat and selective exposure: the moderating role of threat and decision context
      on confirmatory information search after decisions.
AB  - Previous studies on the impact of perceived threat on confirmatory information
      search (selective exposure) in the context of decision making have yielded mixed
      results. Some studies have suggested that confirmatory information search is
      reduced, yet others have found contradictory effects. The present series of 5
      studies consistently found that the crucial moderator for these inconsistent
      findings was whether the induced threat was contextually related to the
      subsequent decision and information search tasks. Contextual incongruence (e.g.,
      an induction of terrorist threat followed by an economic decision case) results
      in reduced levels of confirmatory information search, whereas a congruent threat
      (e.g., an induction of terrorist threat followed by a decision case on terrorism)
      results in increased levels of confirmatory information search. Analyses of the
      underlying psychological processes revealed that decision-unrelated threat
      inductions increase decision makers' experienced decision uncertainty, thus
      reducing confirmatory information search.

PMID- 21171801
TI  - Eliminating inhibition of return by changing salient nonspatial attributes in a
      complex environment.
AB  - Inhibition of return (IOR) occurs when a target is preceded by an irrelevant
      stimulus (cue) at the same location: Target detection is slowed, relative to
      uncued locations. In the present study, we used relatively complex displays to
      examine the effect of repetition of nonspatial attributes. For both color and
      shape, attribute repetition produced a robust inhibitory effect that followed a
      time course similar to that for location-based IOR. However, the effect only
      occurred when the target shared both the feature (i.e., color or shape) and
      location with the cue; this constraint implicates a primary role for location.
      The data are consistent with the idea that the system integrates consecutive
      stimuli into a single object file when attributes repeat, hindering detection of
      the second stimulus. The results are also consistent with an interpretation of
      IOR as a form of habituation, with greater habituation occurring with increasing
      featural overlap of a repeated stimulus. Critically, both of these
      interpretations bring the IOR effect within more general approaches to attention
      and perception, rather than requiring a specialized process with a limited
      function. In this view, there is no process specifically designed to inhibit
      return, suggesting that IOR may be the wrong framing of inhibitory repetition
      effects. Instead, we suggest that repetition of stimulus properties can interfere
      with the ability to focus attention on the aspects of a complex display that are
      needed to detect the occurrence of the target stimulus; this is a failure of
      activation, not an inhibition of processing.

PMID- 21171803
TI  - The representation of abstract words: why emotion matters.
AB  - Although much is known about the representation and processing of concrete
      concepts, knowledge of what abstract semantics might be is severely limited. In
      this article we first address the adequacy of the 2 dominant accounts (dual
      coding theory and the context availability model) put forward in order to explain
      representation and processing differences between concrete and abstract words. We
      find that neither proposal can account for experimental findings and that this
      is, at least partly, because abstract words are considered to be unrelated to
      experiential information in both of these accounts. We then address a particular
      type of experiential information, emotional content, and demonstrate that it
      plays a crucial role in the processing and representation of abstract concepts:
      Statistically, abstract words are more emotionally valenced than are concrete
      words, and this accounts for a residual latency advantage for abstract words,
      when variables such as imageability (a construct derived from dual coding theory)
      and rated context availability are held constant. We conclude with a discussion
      of our novel hypothesis for embodied abstract semantics.

PMID- 21171804
TI  - Retrieval during learning facilitates subsequent memory encoding.
AB  - In multiple-list learning, retrieval during learning has been suggested to
      improve recall of the single lists by enhancing list discrimination and, at test,
      reducing interference. Using electrophysiological, oscillatory measures of brain
      activity, we examined to what extent retrieval during learning facilitates list
      encoding. Subjects studied 5 lists of items in anticipation of a final cumulative
      recall test and did either a retrieval or a no-retrieval task between study of
      the lists. Retrieval was from episodic memory (recall of the previous list),
      semantic memory (generation of exemplars from an unrelated category), or short
      term memory (2-back task). Behaviorally, all 3 forms of retrieval enhanced recall
      of both previously and subsequently studied lists. Physiologically, the results
      showed an increase of alpha power (8-14 Hz) from List 1 to List 5 encoding when
      no retrieval activities were interpolated but no such increase when any of the 3
      retrieval activities occurred. Brain-behavior correlations showed that alpha
      power dynamics from List 1 to List 5 encoding predicted subsequent recall
      performance. The results suggest that, without intermittent retrieval, encoding
      becomes ineffective across lists. In contrast, with intermittent retrieval, there
      is a reset of the encoding process for each single list that makes encoding of
      later lists as effective as encoding of early lists.

PMID- 21171805
TI  - When does length cause the word length effect?
AB  - The word length effect, the finding that lists of short words are better recalled
      than lists of long words, has been termed one of the benchmark findings that any
      theory of immediate memory must account for. Indeed, the effect led directly to
      the development of working memory and the phonological loop, and it is viewed as
      the best remaining evidence for time-based decay. However, previous studies
      investigating this effect have confounded length with orthographic neighborhood
      size. In the present study, Experiments 1A and 1B revealed typical effects of
      length when short and long words were equated on all relevant dimensions
      previously identified in the literature except for neighborhood size. In
      Experiment 2, consonant-vowel-consonant (CVC) words with a large orthographic
      neighborhood were better recalled than were CVC words with a small orthographic
      neighborhood. In Experiments 3 and 4, using two different sets of stimuli, we
      showed that when short (1-syllable) and long (3-syllable) items were equated for
      neighborhood size, the word length effect disappeared. Experiment 5 replicated
      this with spoken recall. We suggest that the word length effect may be better
      explained by the differences in linguistic and lexical properties of short and
      long words rather than by length per se. These results add to the growing
      literature showing problems for theories of memory that include decay offset by
      rehearsal as a central feature.

PMID- 21171806
TI  - Balancing cognitive demands: control adjustments in the stop-signal paradigm.
AB  - Cognitive control enables flexible interaction with a dynamic environment. In 2
      experiments, the authors investigated control adjustments in the stop-signal
      paradigm, a procedure that requires balancing speed (going) and caution
      (stopping) in a dual-task environment. Focusing on the slowing of go reaction
      times after stop signals, the authors tested 5 competing hypotheses for post-stop
      signal adjustments: goal priority, error detection, conflict monitoring,
      surprise, and memory. Reaction times increased after both successful and failed
      inhibition, consistent with the goal priority hypothesis and inconsistent with
      the error detection and conflict hypotheses. Post-stop-signal slowing was greater
      if the go task stimulus repeated on consecutive trials, suggesting a contribution
      of memory. We also found evidence for slowing based on more than the immediately
      preceding stop signal. Post-stop-signal slowing was greater when stop signals
      occurred more frequently (Experiment 1), inconsistent with the surprise
      hypothesis, and when inhibition failed more frequently (Experiment 2). This
      suggests that more global manipulations encompassing many trials affect post-stop
      signal adjustments.

PMID- 21171807
TI  - Metacognition in monkeys during an oculomotor task.
AB  - This study investigated whether rhesus monkeys show evidence of metacognition in
      a reduced, visual oculomotor task that is particularly suitable for use in fMRI
      and electrophysiology. The 2-stage task involved punctate visual stimulation and
      saccadic eye movement responses. In each trial, monkeys made a decision and then
      made a bet. To earn maximum reward, they had to monitor their decision and use
      that information to bet advantageously. Two monkeys learned to base their bets on
      their decisions within a few weeks. We implemented an operational definition of
      metacognitive behavior that relied on trial-by-trial analyses and signal
      detection theory. Both monkeys exhibited metacognition according to these
      quantitative criteria. Neither external visual cues nor potential reaction time
      cues explained the betting behavior; the animals seemed to rely exclusively on
      internal traces of their decisions. We documented the learning process of one
      monkey. During a 10-session transition phase, betting switched from random to a
      decision-based strategy. The results reinforce previous findings of metacognitive
      ability in monkeys and may facilitate the neurophysiological investigation of
      metacognitive functions.

PMID- 21171808
TI  - The world is not flat: can people reorient using slope?
AB  - Studies of spatial representation generally focus on flat environments and visual
      input. However, the world is not flat, and slopes are part of most natural
      environments. In a series of 4 experiments, we examined whether humans can use a
      slope as a source of allocentric, directional information for reorientation. A
      target was hidden in a corner of a square, featureless enclosure tilted at a 5
      degrees  angle. Finding it required using the vestibular, kinesthetic, and visual
      cues associated with the slope gradient. In Experiment 1, the overall sample
      performed above chance, showing that slope is sufficient for reorientation in a
      real environment. However, a sex difference emerged; men outperformed women by
      1.4 SDs because they were more likely to use a slope-based strategy. In
      Experiment 2, attention was drawn to the slope, and participants were prompted to
      rely on it to solve the task; however, men still outperformed women, indicating a
      greater ability to use slope. In Experiment 3, we excluded the possibility that
      women's disadvantage was due to wearing heeled footwear. In Experiment 4, women
      required more time than men to identify the uphill direction of the slope
      gradient; this suggests that, in a bottom-up fashion, a perceptual or attentional
      difficulty underlies women's disadvantage in the ability to use slope and their
      decreased reliance on this cue. Overall, a bi-coordinate representation was used
      to find the goal: The target was encoded primarily with respect to the vertical
      axis and secondarily with respect to the orthogonal axis of the slope.

PMID- 21171810
TI  - Steroids in the treatment of group A streptococcal necrotizing soft tissue
      infection.
AB  - BACKGROUND: Group A streptococcal necrotizing soft-tissue infection with toxic
      shock is a life-threatening disease. Corticosteroid use in the treatment of this
      process has been reported rarely. METHOD: Case reports and review of pertinent
      literature. RESULTS: Two infections caused by the same clonal strain of
      Streptococcus pyogenes are presented. CONCLUSION: The cases illustrate the
      possible utility of high-dose steroids in the treatment of this process.

PMID- 21171811
TI  - Prevention of catheter-related blood stream infection: back to basics?
AB  - BACKGROUND: Central venous catheter (CVC)-related infections are a substantial
      problem in the intensive care unit (ICU). Our infection control team initiated
      the routine use of antiseptic-coated (chlorhexidine-silver sulfadiazine; Chx-SS)
      CVCs in our adult ICUs to reduce catheter-associated (CA) and catheter-related
      (CR) blood stream infection (BSI) as we implemented other educational and best
      practice standardization strategies. Prior randomized studies documented that the
      use of Chx-SS catheters reduces microbial colonization of the catheter compared
      with an uncoated standard (Std) CVC but does not reduce CR-BSI. We therefore
      implemented the routine use of uncoated Std CVCs in our surgical ICU (SICU) and
      examined the impact of this change. HYPOTHESIS: The use of uncoated Std CVCs does
      not increase CR-BSI rate in an SICU. METHODS: Prospective evaluation of universal
      use of uncoated Std CVCs, implemented November 2007 in the SICU. The incidences
      of CA-BSI and CR-BSI were compared during November 2006-October 2007 (universal
      use of Chx-SS CVCs) and November 2007-October 2008 (universal use of Std CVCs) by
      t-test. The definitions of the U.S. Centers for Disease Control and Prevention
      were used for CA-BSI and CR-BSI. Patient data were collected via a dedicated
      Acute Physiology and Chronic Health Evaluation (APACHE) III coordinator for the
      SICU. RESULTS: Annual use of CVCs increased significantly in the last six years,
      from 3,543 (2001) to 5,799 (2006) total days. The APACHE III scores on day 1
      increased from a mean of 54.4 in 2004 to 55.6 in 2008 (p = 0.0010; 95% confidence
      interval [CI] 1.29-5.13). The mean age of the patients was unchanged over this
      period, ranging from 58.2 to 59.6 years. The Chx-SS catheters were implemented in
      the SICU in 2002. Data regarding the specific incidence of CR-BSI were collected
      beginning at the end of 2005, with mandatory catheter tip cultures when CVCs were
      removed. Little difference was identified in the incidence of BSI between the
      interval with universal Chx-SS use and that with Std CVC use. (Total BSI 0.7 vs.
      0.8 per 1,000 catheter days; CA-BSI 0.5 vs. 0.8 per 1,000 catheter days; CR-BSI
      0.2 vs. 0 per 1,000 catheter days.) No difference was seen in the causative
      pathogens of CA-BSI or CR-BSI. CONCLUSION: Eliminating the universal use of Chx
      SS-coated CVCs in an SICU with a low background incidence of CR-BSIs did not
      result in an increase in the rate of CR-BSIs. This study documents the greater
      importance of adherence to standardization of the processes of care related to
      CVC placement than of coated CVC use in the reduction of CR-BSI.

PMID- 21171812
TI  - Bladder pressure measurements are an independent predictor of urinary tract
      infection in trauma patients.
AB  - PURPOSE: To determine the risk factors for urinary tract infections (UTIs)
      specific to trauma patients in order to assist in the development of infection
      control protocols. METHODS: Data were collected prospectively from January 2003
      until December 2005 by an epidemiology nurse and combined with registry data from
      our Level 1 trauma center. The trauma patients admitted to the Surgery and Trauma
      Intensive Care Unit (STICU)(n = 938) who did and did not have UTIs were compared
      for demographics, Injury Severity Score (ISS), and epidemiologic data, including
      use of Foley catheters and bladder pressure measurements (BPMs). An open system
      was used for the measurements in which the catheter was disconnected from the bag
      to instill 50 mL of saline into the bladder, and an 18-gauge needle was inserted
      into the catheter to measure the pressure. RESULTS: A total of 50 patients had no
      Foley catheter or UTIs. Among the 836 patients with catheters but no BPMs, there
      were 36 UTIs (4.31%), whereas the 52 patients with catheters and BPMs had 12 UTIs
      (23.08%)(p < 0.0001). Patients with UTIs were more severely injured older females
      (mean age 40.1 +/- 18.6 years with no UTI vs. 48.5 +/- 20.8 with UTIs; p =
      0.0083; percent female 26.4 no UTI vs. 45.8 UTI; p = 0.007; ISS 19.3 +/- 11.3 no
      UTI vs. 26.2 +/- 11.6; p < 0.0001). Using logistic regression, BPM was an
      independent predictor of UTI, with infection being seven times more likely in the
      patients having the measurements (odds ratio [OR] 6.99; 95% confidence-interval
      [CI] 3.087-15.827). Along with age (OR 1.039; CI 1.024-1.054) and ISS (OR 1.081;
      CI 1.056-1.106), having BPMs was an independent predictor of death (OR 2.475; CI
      1.191-6.328). CONCLUSION: This is the first study that demonstrates a greater
      risk of UTI with BPM using the open technique independent of patient gender or
      degree of injury. Given these findings and a previous trial demonstrating no
      difference in UTI rates with a closed circuit for BPM, our institution has
      incorporated a closed circuit technique into its infection control protocol.

PMID- 21171813
TI  - Transferrin-appended PEGylated nanoparticles for temozolomide delivery to brain:
      in vitro characterisation.
AB  - Polymer-based nanotechnologies are proposed to be an alternative for drug
      administration, delivery and targeting to those of conventional formulations. The
      blood brain barrier is frequently a rate-limiting factor in determining
      permeation of a drug into brain. In this study, the surface-engineered long
      circulating PLGA nanoparticles (NPs) were assessed for brain-specific delivery.
      Long circulating NPs of PLGA- and PEG-synthesised copolymer were prepared by
      emulsification solvent evaporation method. Further, the surface of PEGylated NPs
      was modified by anchoring transferrin (Tf) ligand for receptor-mediated targeting
      to brain. NPs were characterised for shape and size, zeta potential, entrapment
      efficiency and in vitro drug release. In vitro cytotoxicity studies were
      performed on human cancer cell lines. Confocal Laser Scanning Microscopy studies
      show the enhanced uptake of Tf-appended PEGylated NPs and their localisation in
      the brain tissues. Hence, the specific role of Tf ligand on PEGylated NPs for
      brain delivery was confirmed.

PMID- 21171814
TI  - Intracellular drug delivery using polysorbate 80-modified poly(D,L-lactide-co
      glycolide) nanospheres to glioblastoma cells.
AB  - We investigated doxorubicin (DOX)-loaded nanospheres (NS) formulated using a
      biodegradable polymer, poly(D,L-lactide-co-glycolide) (PLGA), for targeted
      chemotherapy of brain tumours. A nonionic surfactant, polysorbate 80 (P80), was
      used to modify the surfaces of PLGA NS to improve cellular drug delivery. DOX
      loaded PLGA NS were formulated by emulsion solvent diffusion and characterised
      for DOX encapsulation and in vitro release. The effectiveness of DOX-loaded P80
      PLGA NS was investigated in A172 human glioblastoma cells. The drug release
      pattern was dependent on the pH of the medium. Quantitatively, the cellular
      uptake of NS was significantly increased by P80 surface modification compared
      with unmodified NS. Confocal laser scanning microscopy studies revealed that DOX
      was released from NS following accumulation in the cell nuclei. DOX-loaded P80
      PLGA NS could significantly inhibit both DOX efflux from the cells and cell
      proliferation compared with a DOX solution.

PMID- 21171815
TI  - Diclofenac-loaded Eudragit S100 nanosuspension for ophthalmic delivery.
AB  - In this study, diclofenac-loaded Eudragit S100-based nanosuspension was prepared
      by nanoprecipitation method and characterised for particle size, morphology, in
      vitro release, and for its in vivo ocular anti-inflammatory activity. The
      diclofenac-loaded Eudragit S100 nanosuspension was found to have a particle size
      of 172 nm, polydispersibility index of 0.14 and zeta potential of -23.7 +/- 6.07
      mV, indicating that the nanosuspension is fairly stable. The nanosuspended
      particles were found to be spherical in shape. The nanosuspension was found to
      provide a sustained in vitro release, following the Higuchi square-root release
      kinetics. The results indicated that the nanosuspension released the drug by
      combination of dissolution and diffusion. The in vivo evaluation of
      nanosuspension in PGE(2)-induced ocular inflammation in rabbit model revealed a
      significantly (p  <  0.05) higher inhibition of PGE(2)-induced polymorphonuclear
      leukocytes migration and lid-closure scores as compared with the aqueous solution
      of diclofenac.

PMID- 21171816
TI  - Preparation and in vitro characterization of vascular endothelial growth factor
      (VEGF)-loaded poly(D,L-lactic-co-glycolic acid) microspheres using a double
      emulsion/solvent evaporation technique.
AB  - Biodegradable Poly(lactic-co-glycolic acid; PLGA), microspheres encapsulating the
      angiogenic protein recombinant human vascular endothelial growth factor (rhVEGF)
      were formed to achieve VEGF release in a sustained manner. These microspheres are
      a promising delivery system which can be used for therapeutic angiogenesis. The
      PLGA microspheres incorporating two different initial loading amounts of rhVEGF
      have been prepared by a modified water-in-oil-in-water (w/o/w) double
      emulsion/solvent evaporation technique. The microspheres have been characterized
      by particle size distribution, environmental scanning electron microscopy (ESEM),
      light microscopy, encapsulation efficiency and their degradation was studied in
      vitro. The rhVEGF released from microspheres was quantified by the competitive
      enzyme-linked immunosorbent assay (ELISA) and human umbilical vein endothelial
      cell (HUVEC) proliferation assay was used to assess biological activity of the
      released VEGF. The microspheres were spherical with diameters of 10-60 um and the
      encapsulation efficiency was between 46% and 60%. The release kinetics of rhVEGF
      was studied for two different amounts: 5 ug VEGF (V5) and 50 ug VEGF (V50) per
      500 mg starting polymer. The total protein (VEGF:BSA) release increased up to 4
      weeks for two rhVEGF concentrations. The ELISA results showed that the burst
      release for V5 and V50 microspheres were 4 and 27 ng/mL, respectively. For V5,
      the microspheres showed an initial burst release, followed by a higher steady
      state release until 14 days. VEGF release increased up to 2 weeks for V50
      microsphere. HUVEC proliferation assay showed that endothelial cells responded to
      bioactive VEGF by proliferating and migrating.

PMID- 21171817
TI  - Microencapsulation of budesonide with dextran by spray drying technique for colon
      targeted delivery: an in vitro/in vivo evaluation in induced colitis in rat.
AB  - The aim of this study was developing colon targeted-delivery of budesonide for
      ulcerative colitis. Microcapsules were prepared using spray drying technique by
      different drug-to-dextran ratios and three molecular weights (MWs) of polymer.
      Differential scanning calorimetry, X-ray diffraction (XRD), drug release and
      loading efficiency of microcapsules were studied. In vivo efficacy of the
      selected formulation prepared by 1 : 10 drug-to-polymer ratio and dextran with MW
      500 000 (D10M500) against acetic acid-induced colitis in rats was evaluated and
      compared to the control and reference groups (mesalasine and budesonide
      suspensions). The results showed that D10M500 microcapsules could target the drug
      to colon and its efficacy in reducing macroscopic damage score was higher than
      mesalasine suspension. Treatment with D10M500 decreased the scores of crypt
      damage and total colitis significantly compared to the control group which just
      received the vehicle and the groups treated with mesalasine and budesonide
      suspension which could not reduce the colitis parameters significantly.

PMID- 21171818
TI  - Preparation and characterization of ibuprofen solid lipid nanoparticles with
      enhanced solubility.
AB  - Solid lipid nanoparticles (SLNs) loaded with ibuprofen (IBU) were prepared by
      solvent-free high-pressure homogenization (HPH). The produced SLNs consisted of
      stearic acid, triluarin or tripalmitin as lipid matrixes and various stabilizers.
      The produced empty and IBU-loaded SLNs were characterized for particle size
      stability over 8 months. Differential scanning calorimetry (DSC) and X-ray
      diffraction (XRD) were implemented to characterize the IBU state of freeze-dried
      SLNs. IBU was found to be in both amorphous and crystalline form within the lipid
      matrix. The lyophilized powders showed increased dissolution rates for IBU
      depending on the lipid nature. SLNs were incubated in Caco-2 cells for 24 h
      showing negligible cell cytotoxicity up to 15 mg/mL.

PMID- 21171819
TI  - Acaricidal activities of clove bud oil and red thyme oil using microencapsulation
      against HDMs.
AB  - The purpose of this study was to produce a safer microcapsule loaded with clove
      bud oil and red thyme oil to reduce the population of house dust mites (HDMs).
      Gelatin-based microcapsules 4-85 um in size were created, with agitation speed
      and type of oil playing a critical role in governing their size. Microcapsules
      made up of single spherical units less than 30 um in diameter remained separate
      on the fibre, whereas larger microcapsules of over 30 um ruptured or aggregated.
      Thermogravimetric analysis (TGA) demonstrated that microcapsules containing red
      thyme oil showed a more consistent range of oil loading, from 50 to 80%, than
      microcapsules containing clove bud oil, which ranged from 30 to 80% (more
      deviated). Mortality tests on Dermatophagoides farinae conducted on fabric with
      attached microcapsules showed that clove bud oil, containing a more phenolic
      monoterpenoid (eugenol), was more effective at reducing the live HDMs (94%
      mortality).

PMID- 21171820
TI  - The inhibition of stuttering via the perceptions and production of syllable
      repetitions.
AB  - In contrast to most therapeutic protocols for stuttering that induce fluency
      while producing speech targets, we investigated the possibility of inducing
      "carry-over" fluency prior to normal speech production. Ten adults who stutter
      read 7-12 syllable phrases after actively producing (via shadowing) or passively
      listening to: (a) repeating syllables, matched to the initial syllable of the
      target utterance; (b) repeating syllables, not matched to the initial syllable of
      the target; (c) nonrepeating syllables; and (d) fricative /noise-like acoustic
      signals. Relative to baseline, all active syllabic conditions produced
      approximately 70% inhibition (reduction) of stuttering in the ensuing target
      utterances, which is attributed to carry-over from fluent shadowing. The most
      robust passive inhibition (56%) resulted from listening to matched repeating
      syllables. These findings further sustain that a perception-production link in
      speech, possibly resulting from mirror neuron activity, can facilitate the
      inhibition of stuttering. However, in this study we further demonstrate gestural
      and temporal flexibility of this mechanism, showing that this inhibitory strategy
      may be enacted prior to producing speech targets. We discuss possible clinical
      implications and draw comparisons between core stuttering behaviors (i.e.,
      repetitions and prolongations) and behavioral therapeutic strategies (e.g.,
      slowed speech, preparatory sets) used to inhibit or eliminate stuttering.

PMID- 21171822
TI  - Differential surface antigen expression and 1alpha,25-dihydroxyvitamin D3
      responsiveness distinguish human dermal fibroblasts with age-dependent osteogenic
      differentiation potential from marrow-derived stromal cells in vitro.
AB  - BACKGROUND AIMS: Recent studies have demonstrated that cells committed to a
      fibroblastic lineage, including dermal fibroblasts, may undergo osteoblastic
      differentiation when treated with steroid hormones. However, stem cells have also
      been isolated from the dermis, making it unclear whether osteoinduction of dermal
      fibroblasts is the result of transdifferentiation of committed fibroblasts or
      differentiation of resident multipotent stromal cells, which are morphologically
      indistinguishable. METHODS: Flow cytometry was used to characterize the
      expression of CD26, CD90 and CD105 on neonatal and adult human dermal fibroblasts
      and adult human bone marrow-derived stromal cells. These cells were then cultured
      with the steroid hormones 1alpha,25-dihydroxyvitamin D(3) and dexamethasone, and
      evaluated for protein expression and mineral deposition typical of an
      osteoblastic phenotype. RESULTS: The surface peptidase, dipeptidyl peptidase IV
      (CD26), was differentially expressed between human neonatal (98.22 +/- 1.47%) and
      adult (90.73 +/- 7.97%) dermal fibroblasts and adult bone marrow-derived stromal
      cells (6.84 +/- 5.07%). In addition, neonatal dermal fibroblasts treated with
      vitamin D(3) expressed alkaline phosphatase, osteocalcin and bone sialoprotein,
      and deposited mineral, which is consistent with an osteoblastic phenotype. Such
      differentiation was not observed in adult dermal fibroblasts. In contrast, marrow
      derived stromal cells required dexamethasone in order to undergo osteoblastic
      differentiation. CONCLUSIONS: Taken together, the differential surface antigen
      expression and disparate response to steroid hormones suggest that committed
      neonatal dermal fibroblasts are distinct from mesenchymal stromal cells and
      possess osteogenic differentiation potential.

PMID- 21171823
TI  - Effect of cell-seeding density on the proliferation and gene expression profile
      of human umbilical vein endothelial cells within ex vivo culture.
AB  - BACKGROUND AIMS: Characterization of endothelial cell-biomaterial interaction is
      crucial for the development of blood-contacting biomedical devices and implants.
      However, a crucial parameter that has largely been overlooked is the cell-seeding
      density. METHODS: This study investigated how varying cell-seeding density
      influences human umbilical vein endothelial cell (HUVEC) proliferation on three
      different substrata: gelatin, tissue culture polystyrene (TCPS) and poly-l-lactic
      acid (PLLA). RESULTS: The fastest proliferation was seen on gelatin, followed by
      TCPS and PLLA, regardless of seeding density. On both TCPS and gelatin, maximal
      proliferation was attained at an initial seeding density of 1000 cells/cm(2). At
      seeding densities above and below 1000 cells/cm(2), the proliferation rate
      decreased sharply. On PLLA, there was a decrease in cell numbers over 7 days of
      culture, below a certain threshold seeding density (c. 2500-3000 cells/cm(2)),
      which meant that some of the cells were dying off rather than proliferating.
      Above this threshold seeding density, HUVEC displayed slow proliferation.
      Subsequently, quantitative real-time polymerase chain reaction (RT-qPCR) analysis
      of eight gene markers associated with adhesion and endothelial functionality
      (VEGF-A, integrin-alpha5, VWF, ICAM1, ICAM2, VE-cadherin, endoglin and PECAM1)
      was carried out on HUVEC seeded at varying densities on the three substrata. A
      significant downregulation of gene expression was observed at an ultralow cell
      seeding density of 100 cells/cm(2). This was accompanied by an extremely slow
      proliferation rate, probably because of an acute lack of intercellular contacts
      and paracrine signaling. CONCLUSION: Hence, this study demonstrates that seeding
      density has a profound effect on the proliferation and gene expression profile of
      endothelial cells seeded on different biomaterial surfaces.

PMID- 21171821
TI  - Epigenetic modulation of MAGE-A3 antigen expression in multiple myeloma following
      treatment with the demethylation agent 5-azacitidine and the histone deacetlyase
      inhibitor MGCD0103.
AB  - BACKGROUND AIMS: Immunotherapy targeting MAGE-A3 in multiple myeloma (MM) could
      eradicate highly aggressive and proliferative clonal cell populations responsible
      for relapse. However, expression of many cancer-testis antigens, including MAGE
      A3, can be heterogeneous, leading to the potential for tumor escape despite MAGE
      A3-induced immunity. We hypothesized that a combination of the hypomethylating
      agent 5-azacitidine (5AC) and the histone deacetylase inhibitor (HDACi) MGCD0103
      (MGC) could induce MAGE-A3 expression in MAGE-A3-negative MM, resulting in
      recognition and killing of MM cells by MAGE-A3-specific cytotoxic T lymphocytes
      (CTL). METHODS: Gene expression analyses of MAGE-A3 expression in primary MM
      patient samples at diagnosis and relapse were completed to identify populations
      that would benefit from MAGE-A3 immunotherapy. MM cell lines were treated with
      5AC and MGC. Real-time polymerase chain reaction (PCR) and Western blotting were
      performed to assess MAGE-A3 RNA and protein levels, respectively. Chromium
      release assays and interferon (IFN) secretion assays were employed to ascertain
      MAGE-A3 CTL specificity against treated targets. RESULTS: Gene expression
      analysis revealed that MAGE-A3 is expressed in MM patients at diagnosis (25%) and
      at relapse (49%). We observed de novo expression of MAGE-A3 RNA and protein in
      MAGE-A3-negative cell lines treated with 5AC. MGC treatment alone did not induce
      expression but sequential 5AC/MGC treatment led to enhanced expression and
      augmented recognition by MAGE-A3-specific CTL, as assessed by (51)Cr-release
      assays (P = 0.047) and enzyme-linked immunosorbent assay (ELISA) for IFN-gamma
      secretion (P = 0.004). CONCLUSIONS: MAGE-A3 is an attractive target for
      immunotherapy of MM and epigenetic modulation by 5AC, and MGC can induce MAGE-A3
      expression and facilitate killing by MAGE-A3-specific CTL.

PMID- 21171824
TI  - Mesenchymal stromal cells inhibit Th17 but not regulatory T-cell differentiation.
AB  - BACKGROUND AIMS: A previous study has demonstrated that mouse mesenchymal stromal
      cells (MSC) produce nitric oxide (NO), which suppresses signal transducer and
      activator of transcription (STAT) 5 phosphorylation and T-cell proliferation
      under neutral and T helper 1 cells (Th1) conditions. We aimed to determine the
      effects of MSC on T helper 17 cells (Th17) and regulatory T-cell (T-reg)
      differentiation. METHODS: CD4 T cells obtained from mouse spleen were cultured in
      conditions for Th17 or Treg differentiation with or without mouse MSC. Th17 and
      Treg differentiation was assessed by flow cytometry using antibodies against
      interleukin (IL)-17 and forkhead box P3 (Foxp3), a master regulator of Treg
      cells. RESULTS: MSC inhibited Th17 but not Treg differentiation. Under Th17
      conditions, MSC did not produce NO, and inhibitors of indoleamine-2,3-dioxygenase
      (IDO) and prostaglandin E(2) (PGE2) both restored MSC suppression of
      differentiation, suggesting that MSC suppress Th17 differentiation at least in
      part through PGE2 and IDO. CONCLUSIONS: Our results suggest that MSC regulate CD4
      differentiation through different mechanisms depending on the culture conditions.

PMID- 21171825
TI  - CXCR4 and matrix metalloproteinase-2 are involved in mesenchymal stromal cell
      homing and engraftment to tumors.
AB  - BACKGROUND AIMS: Bone marrow-derived mesenchymal stromal cells (BMSC) have been
      shown to migrate to injury, ischemia and tumor microenvironments. The mechanisms
      by which mesenchymal stromal cells (MSC) migrate across endothelium and home to
      the target tissues are not yet fully understood. METHODS: We used rat BMSC to
      investigate the molecular mechanisms involved in their tropism to tumors in vitro
      and in vivo. RESULTS: BMSC were shown to migrate toward four different tumor
      cells in vitro, and home to both subcutaneous and lung metastatic prostate tumor
      models in vivo. Gene expression profiles of MSC exposed to conditioned medium
      (CM) of various tumor cells were compared and revealed that matrix
      metalloproteinase-2 (MMP-2) expression in BMSC was downregulated after 24 h
      exposure to tumor CM. Chemokine (C-X-C motif) Receptor 4 (CXCR4) upregulation was
      also found in BMSC after 24 h exposure to tumor CM. Exposure to tumor cell CM
      enhanced migration of BMSC toward tumor cells. Stromal Cell-Derived Factor (SDF
      1) inhibitor AMD3100 and MMP-2 inhibitor partly abolished the BMSC migration
      toward tumor cells in vitro. CONCLUSIONS: These results suggest that the CXCR4
      and MMP-2 are involved in the multistep migration processes of BMSC tropism to
      tumors.

PMID- 21171826
TI  - A simple method for identifying bone marrow mesenchymal stromal cells with a high
      immunosuppressive potential.
AB  - BACKGROUND AIMS: The beneficial activity of mesenchymal stromal cells (MSC) in
      allogeneic hematopietic stem cell transplantation requires correct use in terms
      of cell dose and timing of infusion and the identification of biomarkers for
      selection. The immunosuppressive bone marrow (BM)-derived MSC (BM-MSC) functions
      have been associated with the production of soluble HLA-G molecules (sHLA-G) via
      interleukin (IL)-10. We have established a reliable method for evaluating BM-MSC
      HLA-G expression without the influence of peripheral blood mononuclear cells
      (PBMC). METHODS: Thirteen BM-MSC from donors were activated with recombinant IL
      10 or co-cultured with 10 different phytohemagglutinin (PHA)-treated PBMC (PHA
      PBMC). Membrane-bound and sHLA-G expression was evaluated by flow cytometry and
      enzyme-linked immunosorbent assay (ELISA), respectively; lymphoproliferation was
      measured by (methyl-(3)H)thymidine. RESULTS: The results demonstrated the ability
      of IL-10 to stimulate both membrane-bound and sHLA-G production by BM-MSC. The
      levels of HLA-G expression induced by IL-10 in BM-MSC were associated with the
      inhibition of PHA-PBMC proliferation (sHLA-G, P = 0.0008, r = 0.9308; membrane
      HLA-G, P = 0.0005, r = 0.9502). CONCLUSIONS: We propose the evaluation of sHLA-G
      production in IL-10-treated BM-MSC cultures as a possible marker of
      immunoregulatory function.

PMID- 21171827
TI  - A comparative study of three methods to evaluate an intervention to improve
      empirical antibiotic therapy for acute bacterial infections in hospitalized
      patients.
AB  - BACKGROUND: In order to limit the use of broad-spectrum antibiotics, standardized
      empirical therapy against acute bacterial infections has been advocated. METHODS:
      Guidelines for acute bacterial infections recommending increased usage of
      benzylpenicillin and restricted use of fluoroquinolones and cephalosporins have
      been implemented in Kalmar County, Sweden. We evaluated this strategy by
      recording therapy in patients with bacteraemia, antibiotic requisition, and point
      prevalence surveys prior to this intervention and at 6 and 12 months after.
      RESULTS: Comparing the methods simultaneously, there was good agreement between
      them and an overall significant change in antibiotic usage. There was a
      significant shift from cefuroxime to cefotaxime and a borderline significant
      increase in the use of benzylpenicillin (p = 0.057). Based on the defined daily
      dose (DDD), a highly significant decrease in total cefotaxime and cefuroxime
      usage was observed that was not detected when applying the prescribed daily dose
      (PDD), which is adapted to local treatment practices. No change was found in
      mortality in Staphylococcus aureus bacteraemia or the incidence of Clostridium
      difficile infection. CONCLUSIONS: We conclude that the implementation of the new
      guidelines has resulted in a significant change in antibiotic usage, which could
      be conveniently monitored by antibiotic requisition if PDD is used in addition to
      DDD.

PMID- 21171828
TI  - A search for the 'Holy Grail' in the evaluation of febrile neonates aged 28 days
      or less: a prospective study.
AB  - OBJECTIVE: To determine the reliability of low-risk criteria to exclude serious
      bacterial infection (SBI) in febrile neonates aged <=28 days. METHODS: All
      febrile neonates who were hospitalized for fever evaluation were prospectively
      divided into 2 groups by risk status for SBI. The following criteria were used to
      define low risk: (1) unremarkable medical history; (2) well-appearing; (3) no
      focal signs of infection; (4) white blood cell count between 5000 and
      15,000/mm(3); (5) normal urinalysis; (6) no mucoid or bloody diarrhoea. RESULTS:
      Of the 465 enrolled neonates, 177 (38.1%) were considered high risk for SBI and
      288 (61.9%) low risk. SBIs were found in 55 (31.1%) neonates in the high-risk
      group compared to 10 (3.5%) in the low-risk group (p < 0.001). The sensitivity,
      specificity, positive predictive value and negative predictive value of the
      criteria for all types of SBI were 84.6% (95% confidence interval (CI) 73.9
      91.4%), 69.5% (95% CI 64.8-73.8%), 31% (95% CI 27.3-35.1%) and 96.5% (95% CI 94.3
      98%), respectively. CONCLUSIONS: The defined criteria are not sufficiently
      reliable to exclude an SBI or an invasive SBI. We therefore suggest that all
      febrile neonates in this age group should be hospitalized for complete evaluation
      and consideration of empirical intravenous antibiotic treatment.

PMID- 21171829
TI  - The annual costs associated with human papillomavirus types 6, 11, 16, and 18
      infections in Finland.
AB  - OBJECTIVES: It is known that infections with human papillomavirus (HPV) types 6,
      11, 16, and 18, cause cervical cancers (CC), cervical intraepithelial neoplastic
      lesions (types 1 to 3; CIN 1-3), and genital warts (GW). Together with equivocal
      cytological abnormalities (ECA), these place a considerable burden on society,
      but the costs and resource usage are not easily estimated. Therefore, we
      undertook this study to estimate the burden and costs associated with HPV-related
      diseases. METHODS: We used Finnish registry-based data for CC, CIN 1-3 and ECA.
      Data on GW were estimated from associated procedures and medications. The annual
      burden of disease was estimated from hospitalizations, visits to specialists and
      primary level care, and pharmaceutical use. The evaluation of costs included
      health care and screening costs, and productivity lost (separately). Due to the
      data obtained being fragmented, 2 cost scenarios were constructed. RESULTS: The
      follow-up of ECA appears to be the most important cost driver. GW should not be
      underestimated as they affect both genders at an early age. CONCLUSIONS: HPV
      infections are a burden to society, not only as a result of cancer-related costs,
      but also costs related to other diseases and indirect costs in the form of lost
      productivity.

PMID- 21171830
TI  - Experience of meaning in everyday occupations among unemployed people with severe
      mental illness.
AB  - The aim of this qualitative study was to examine the different facets of meaning
      that people who are severely mentally ill and unemployed may find in their
      everyday occupations. Twelve unemployed people with severe mental illness, six
      who attended day centres and six who did not, were interviewed regarding their
      experience of meaning in everyday occupations. The data were analysed with
      content analysis. The results showed that meaning was experienced when feeling
      competent and having a balance between different meaningful occupations that
      helped the informants control their mental illness. Themes of meaning were: being
      socially engaged, feeling competent and accepted by society, creating routines
      and being productive, being creative and seeking knowledge, and taking care of
      body and mind. Substitutes for paid work were found in occupations such as taking
      care of the household or being productive at a day centre. The results suggest
      that people with severe mental illness should be encouraged to play an active
      role in their rehabilitation process, and receive support from the occupational
      therapist in addressing aspects such as forming a social network and daily
      routines, and finding a balance between work-like occupations and rest.

PMID- 21171831
TI  - Upper airway changes in severe obstructive sleep apnea: upper airway length and
      volumetric analyses using 3D MDCT.
AB  - CONCLUSION: Three-dimensional multi-detector computed tomography (3D MDCT)
      analysis of the upper airway suggested that the lengthening of the upper airway
      in the absence of volumetric change may independently contribute to the severity
      of obstructive sleep apnea syndrome (OSAS) in adults. OBJECTIVES: We sought to
      investigate the relationships among the length and volume of the upper airway to
      the severity of OSAS. METHODS: A total of 73 subjects underwent 3D MDCT scanning
      and standard polysomnography. We measured the upper airway length (UAL), which
      was defined as the vertical distance from the hard palate to the hyoid in the mid
      sagittal plane. We also used the height-adjusted UAL for analyses. Upper airway
      volume was measured using a 3D reconstruction of the cross-sectional area from
      the hard palate to the hyoid. RESULTS: The adjusted UAL showed a significant
      positive correlation with the apnea hypopnea index (AHI, r = 0.523, p < 0.000)
      and was a significant variable for predicting the AHI of OSAS patients in
      multiple stepwise regression analysis. Although the severe OSAS group had a
      greater adjusted UAL compared with that of other groups (p = 0.001), the volume
      of the upper airway did not show differences among groups.

PMID- 21171832
TI  - Aerodynamic characteristics of the slit-like trachea-esophagus puncture for voice
      rehabilitation following total laryngectomy.
AB  - CONCLUSIONS: The slit-like trachea-esophagus puncture is a reliable procedure to
      restore the voice in the patient who has undergone a total laryngectomy. The new
      voice quality could be similar to normal and could meet the patient's daily
      needs. OBJECTIVES: We report a new method of tracheoneoesophageal (TE) voice
      rehabilitation. A slit-like trachea-esophagus puncture was made in the
      tracheoesophageal wall after the total laryngectomy. No voice prosthesis was
      used. The purpose of this study was to observe its aerodynamic characteristics.
      METHODS: All 60 patients received voice rehabilitation with the slit-like fistula
      after total laryngectomy. All patients' voices were evaluated as excellent. The
      aerodynamic characteristics of trachea-esophagus voices were observed. RESULTS:
      When a patient attempted to phonate, the upper esophagus was closed. Then, the
      hypopharyngeal cavity expanded. Just before phonating, the upper esophagus was
      full of air as a ball. The air flow escaped through the segment of the trachea
      esophagus slit and entered the pharyngoesophageal segment (PES). The esophageal
      meatus opened. It was vibrated together with nearby mucus and mucosa to form the
      voice. The maximum phonation time of the slit-like fistula voice was not
      significantly different from the Blom-Singer prosthesis voice. Its sound
      intensity was similar to the normal voice.

PMID- 21171833
TI  - Cochlear implant in Cogan syndrome.
AB  - CONCLUSIONS: Despite the need for special fitting strategies, improvements in
      speech discrimination tests support the use of cochlear implantation (CI) for
      patients with Cogan syndrome. Adequate preimplant counselling is mandatory, to
      prevent high expectations and to stress the necessity for bilateral implantation.
      OBJECTIVE: In 60% of patients with Cogan syndrome, CI remains the only treatment
      option. Literature data agree that once the electrode array is properly inserted,
      functional outcomes are very good. Nevertheless, results may deteriorate due to
      progressive cochlear ossification. A few studies have documented the outcomes of
      CI in these patients, but none have reported the long-term results. METHODS: This
      was a retrospective study describing the outcomes of 3 implanted patients with
      Cogan syndrome--among 300 adult patients who received a cochlear implant, 3 had
      become deaf due to Cogan syndrome. RESULTS: In one patient the cochlear
      ossification advanced and the speech perception abilities worsened from the
      highest category to identification of words in closed set. The second patient
      complained of an abrupt reduction of loudness at 18 months post-implant, which
      required an increased electrical stimulation. The third patient reached the
      identification category probably due to auditory dyssynchrony, as an atypical
      consequence of the syndrome.

PMID- 21171834
TI  - Endothelial progenitor cells in sudden sensorineural hearing loss.
AB  - CONCLUSIONS: Endothelial progenitor cells (EPCs) are a unique subtype of
      circulating cells with properties similar to those of embryonal angioblasts. They
      have the potential to proliferate and to differentiate into mature endothelial
      cells. EPCs are reduced in patients with vascular risk factors due to a decreased
      mobilization, an increased consumption at the site of damage or a reduced half
      life. The results of this study confirm the existence of an endothelial
      dysfunction in patients with sudden sensorineural hearing loss (SSHL) and support
      the vascular involvement in the pathogenesis of the disease. OBJECTIVE: The aim
      of this study was to evaluate the concentration of EPCs in patients affected by
      SSHL. METHODS: Twenty-one patients affected by SSHL were evaluated. The number of
      EPCs was analyzed by flow cytometry analysis of peripheral blood CD34+KDR+CD133+
      cells. RESULTS: Circulating levels of EPCs were significantly lower in SSHL
      patients compared with controls. In particular, CD34+KDR+ cells and
      CD34+CD133+KDR+ cells were significantly reduced (p < 0.05).

PMID- 21171835
TI  - Tone perception and production in pediatric cochlear implants users.
AB  - CONCLUSIONS: In prelingually deaf children with cochlear implants, tone
      perception and production performance are highly correlated. This result is
      consistent with the hypothesis that tone perception is the prerequisite for good
      tone production. OBJECTIVES: Previous research has shown remarkable deficits in
      tone perception and production in native tone language-speaking, prelingually
      deafened children with cochlear implants. The purpose of the present study was to
      investigate the relationship between tone perception and production in those
      children. METHODS: Twenty-five prelingually deaf children with cochlear implants
      participated in the study. All subjects were Advanced Bionics CII/90K users with
      various lengths of implant use. To evaluate tone perception performance, subjects
      completed a computerized tone contrast test. For tone production performance, an
      artificial neural network was used to evaluate the accuracy of tones recorded
      from each of the 25 subjects. RESULTS: Large individual differences in tone
      perception and production performance were observed in these subjects. Tone
      perception accuracy ranged from 50.0 to 96.9% correct (chance performance = 50%
      correct; mean = 71.0% correct). Tone production performance ranged from 19.4 to
      97.2% correct (mean = 52.0% correct). A strong correlation was found between tone
      perception and production performance in this group of subjects (r = 0.805).

PMID- 21171836
TI  - Sexual self-perception in schizophrenic and depressive patients.
AB  - BACKGROUND: Sexual self-perception is just one of the items of the complex system
      of self, which has rarely been researched in the population of mental health
      patients. OBJECTIVE: Our goal was to establish whether the differences in sexual
      self-perception exist between schizophrenic and depressive patients compared with
      the healthy control group. PARTICIPANTS AND METHODS: This research was performed
      on 100 schizophrenic patients, 100 depressive patients and 100 phenotypically
      healthy volunteers. In order to diagnose schizophrenia and depression, DSM-IV
      classification was used. Bezinovic's questionnaire for sexual self-perception was
      used in order to assess seven aspects of sexual self-perception. RESULTS: Results
      revealed that schizophrenic and depressive patients, compared with healthy
      individuals, scored significantly higher on the aspects of negative emotionality
      and sexual incompetence, and significantly lower on the aspect of sexual
      satisfaction. No statistically significant differences were established between
      schizophrenic and depressive patients. CONCLUSION: We can conclude that patients
      suffering from schizophrenia or depression differ from healthy individuals in all
      of the aspects of sexual self-perception.

PMID- 21171837
TI  - Preventing repetition of attempted suicide--II. The Amager project, a randomized
      controlled trial.
AB  - Repetition after attempted suicide is high but only few effect studies have been
      carried out. The Baerum Model from Norway offers practical and affordable
      intervention for those not being offered psychiatric treatment. During a period
      from 2005-2007, all attempted suicide patients except those with major
      psychiatric diagnoses (schizophrenia, bipolar disorder, severe/psychotic
      depression), were offered participation. The intervention group received the OPAC
      programme (outreach, problem solving, adherence, continuity) and the control
      group received treatment as usual (TAU). The intervention period was 6 months.
      After this intervention period, all patients were followed passively for an extra
      6 months. The design was an intent-to-treat one. The outcomes were: 1) repetition
      of attempted suicide or suicide, and 2) total number of suicidal acts. A total of
      200 patients were offered participation, 67 refused. Of the 133 participants, 69
      were randomized to the OPAC programme and 64 to the (non-intervention) control
      group. Four in each group dropped out after initial participation. There was a
      significant lower proportion who repeated a suicide attempt the intervention
      group (proportion 8.7%) than in the control group (proportion 21.9%) and the
      number of repetitive acts was also significant lower (eight repetitions in the
      intervention group vs. 22 in the control group). In conclusion, our findings
      suggest a protective effect of the OPAC programme on the proportion who repeated
      a suicide attempt and on the total number of repetitions during the follow-up.

PMID- 21171838
TI  - Pharmacokinetics of voriconazole in adult mallard ducks (Anas platyrhynchos).
AB  - The pharmacokinetics of voriconazole (VRC) administered intravenously (IV) or
      orally (PO; with and without liquid diet) to mallard ducks were studied. Dose
      range, drug bioavailability, and single and multiple treatment pharmacokinetics
      studies were performed. Plasma samples were collected for ultra performance
      liquid chromatography (UPLC) or bioassay analysis. Tissue samples were collected
      for high performance liquid chromatography (HPLC) analysis and histology. No
      overt signs of toxicity were observed during any of the studies regardless of
      administration route, and no histologic lesions/changes were attributed to VRC
      treatment. Average +/- SD bioavailability after a single oral dose was 60.7% +/-
      16.5. Based on a targeted minimum inhibitory concentration of 0.5 MUg/ml VRC, a
      dose of 20 mg per kg body weight for the multi-dose pharmacokinetic study was
      selected. Pharmacokinetic parameter differences between birds dosed with VRC,
      with or without liquid diet, were not clinically significant. The bioassay had an
      overall positive bias (+23.5%) compared to the UPLC. Single or multiple-day VRC
      dosing via IV or PO routes at differing dosages resulted in tissue concentrations
      that were below the HPLC assay's limit of detection (0.1 MUg VRC per g tissue).
      This study indicates that treatment of mallard ducks with VRC might require a
      dosing interval of at least every 8-12 h at a dose of 20 mg/kg, but further
      studies are necessary.

PMID- 21171839
TI  - Applying conversation analysis to traumatic brain injury: investigating touching
      another person in everyday social interaction.
AB  - PURPOSE: Touching others, particularly the opposite sex, is a relatively common
      and problematic behaviour evident in many people with traumatic brain injury
      (TBI), in particular males. Here, we analyse this behaviour in a man with TBI
      (Richard) who regularly engages in inappropriate touching of women. The article
      draws on video-recordings of two naturally occurring social interactions between
      Richard and Joan (one of his carers) to analyse all six instances within these
      interactions where Richard touches Joan. METHOD: The recordings were made by
      leaving a video-recorder in Richard's home where he is supported by members of a
      care team. The socio-linguistic method of conversation analysis was used to
      transcribe and analyse the data. RESULTS: The analysis shows that each of the six
      instances of the touching behaviour occurred not as a random or isolated event in
      the interaction but rather in accompaniment with talk as part of a particular
      conversational action. Specifically, the conversational action in each case was
      produced in an emphatic or heightened style, with this style constituted by
      Richard touching Joan as well as by his use of a number of other resources such
      as eye gaze and the use of stress. CONCLUSIONS: The analysis suggests that the
      touching behaviours in this case were linked not so much to physical
      opportunities (which were available through much of these interactions) but
      rather to what conversational action was being produced at that particular
      sequential context within the interaction. For example, several instances of
      touching occurred as part of emphatically produced conversational actions where a
      previous, non-emphatic, production of that action had not been accepted or
      responded to by Joan. Clinical implications, such as suggestions for prophylactic
      management on the part of those interacting with people with TBI, are discussed.

PMID- 21171840
TI  - Problems with accessibility to health services by persons with disabilities in
      Sao Paulo, Brazil.
AB  - PURPOSE: To describe the occurrence of self-reported problems of accessibility to
      health services used by persons with disabilities in terms of social and health
      services variables. METHODS: We performed a cross-sectional household survey
      designed to assess problems with accessibility to health services faced by
      persons with disabilities. We interviewed 333 persons in Sao Paulo city, in 2007.
      Variables related to the presence of accessibility problems, disabilities,
      gender, age, family head income, ethnicity, use of health services and others
      were analysed using frequencies, percentages, chi(2)-test, ANOVA and Poisson
      regression models. RESULTS: 15.92% of the interviewed persons reported problems
      with accessibility to health services. Persons having multiple (prevalence
      ratios; PR = 2.91) or mobility disability (PR = 6.46) had more problems with
      accessibility than persons with hearing disability. Persons younger than 78 years
      old had more problems with accessibility; those who needed help to go to the
      health service (PR = 3.01) also. CONCLUSIONS: Persons with multiple or mobility
      disability, younger than 78 years, and those who needed help of others to go to
      the health service were more likely to have problems with accessibility to health
      services. This information could be one of the first steps to the management
      and/or planning of appropriate health services for persons with disabilities.

PMID- 21171841
TI  - Group aquatic training improves gait efficiency in adolescents with cerebral
      palsy.
AB  - PURPOSE: To evaluate the effect and feasibility of a 10-week group aquatic
      training programme on gait efficiency in adolescents with cerebral palsy (CP).
      The secondary purpose was to determine the exercise intensity during aquatic
      training in a heterogeneous group of adolescents with CP and to investigate the
      impact of the training programme on the musculoskeletal system. METHOD: Twelve
      ambulatory adolescents with spastic CP were recruited. They participated in 20
      aquatic training sessions (45 min twice a week). Three physical therapists and a
      sports teacher supervised the training sessions. Participants wore a heart rate
      monitor to assess sessions' intensity and a floatation device as appropriate. The
      primary outcome measure was gait efficiency as measured by the gait energy
      expenditure index (EEI). The secondary measures were (1) gait spatiotemporal
      parameters, (2) maximal isometric knee strength and (3) gross motor function.
      RESULTS: Ten adolescents completed the training programme. No adverse effect was
      reported. Average exercise intensity was mild to moderate for more than half of
      the training session. A significant reduction of the EEI and the heart rate
      during walking was observed following the training programme. No significant
      change was observed on secondary outcome measures. CONCLUSIONS: Group aquatic
      training increases gait efficiency in adolescents with CP. This improvement is
      related to systemic cardiorespiratory adaptations. Group aquatic training
      programme is feasible in adolescents presenting CP at different levels of
      severity.

PMID- 21171842
TI  - A framework for evaluating community-based rehabilitation programmes in Chinese
      communities.
AB  - PURPOSE: The primary aim of this study was to develop an evaluation framework
      that could effectively describe the quality of community-based rehabilitation
      (CBR) practice in Chinese communities. METHOD: This study adopted a case study
      approach to build and validate a CBR evaluation framework. Core elements of CBR
      programmes were defined from the literature to form an Initial Framework. Domains
      and elements of the Initial Framework were then verified with examples of CBR
      programmes cited in published articles. The revised framework was then further
      tested for relevance and appropriateness in the real life context through testing
      in five Chinese CBR programmes. RESULTS: A final framework for evaluating CBR
      programmes was developed. It consists of 5 domains, 25 categorised core elements
      and 72 indicators. CONCLUSION: A comprehensive CBR evaluation framework was built
      and initially verified with domains, elements and indicators, and is ready for
      use in Chinese CBR settings.

PMID- 21171843
TI  - Exploring the return-to-work process for workers partially returned to work and
      partially on long-term sick leave due to common mental disorders: a qualitative
      study.
AB  - PURPOSE: We conducted a qualitative study into the return-to-work process of
      workers partially on sick leave due to common mental disorders. Our objectives
      were to describe the barriers to a full return to work, solutions, communicating
      to the working environment and the aim of a full return to work, all as perceived
      by the workers. METHOD: Workers who had partially returned to work and were
      partially on long-term sick leave due to a stress-related, anxiety or depressive
      disorder were eligible for this study. Fourteen workers were interviewed and the
      interviews were transcribed verbatim and coded. RESULTS: The perceived main
      barriers were: inability to set limits, recognise exhaustion and to control
      cognitions and behaviour such as perfectionism. A general pattern in the process
      was that all workers perceived barriers to a full return to work; most workers
      were able to mention solutions; all workers aimed for a full return to work, and
      after some time all workers were met with sufficient understanding and social
      support from their supervisor and health care professional. However, hardly any
      worker intended to implement or utilise the solutions at the workplace, except
      the structural adaptations of the work demands. CONCLUSIONS: The pattern we found
      suggests a critical intention-behaviour gap between solutions and intentions for
      a full return to work and its implementation at work. This implies that we should
      develop new interventions that focus on helping workers and their environment to
      bridge this gap.

PMID- 21171844
TI  - Phase I evaluation of the television assisted prompting system to increase
      completion of home exercises among stroke survivors.
AB  - PURPOSE. Effective delivery of dysphagia exercises requires intensive repetition,
      yet many brain injury survivors demonstrate difficulty adhering to home
      programmes. The Television Assisted Prompting (TAP) system provides a novel
      method to deliver intensive in-home therapy prompts. Specific research questions
      compared the effectiveness of the TAP system to typical practice on programme
      adherence, satisfaction and caregiver burden. METHOD. A within-participant
      alternating treatment design with random assignment of treatment condition
      compared exercise programme adherence across TAP and typical practice delivery
      conditions, replicated across three participants. Data included quantitative
      programme completion rates, satisfaction survey reports and caregiver burden
      questionnaire results, as well as qualitative interview findings. RESULTS. A
      large treatment effect was demonstrated for two participants; exercise programme
      completion rates increased by 6-17 times typical practice levels with the TAP
      system. TAP supported sustained practice over the course of the experiment for
      the third participant despite minimal differences between conditions.
      Participants reported high satisfaction and endorsed the TAP system. There was no
      significant change in caregiver burden. CONCLUSION. The TAP system provided a
      novel assistive tool to support home programme completion of intensive exercise
      regimens for clients with cognitive impairment and care providers with
      significant burden. Future research must ensure continued development of a
      reliable and intuitive system.

PMID- 21171845
TI  - Botulism, where are we now?
AB  - INTRODUCTION: Botulism is a neuroparalytic illness caused by botulinum toxin, a
      product of the Clostridium botulinum bacteria and characteristically presents as
      an acute, symmetrical, descending flaccid paralysis. Albeit it is the most
      poisonous substance known, which even poses a major threat as biological weapons,
      purified and highly diluted botulinum toxin can be used to treat a wide variety
      of conditions associated with muscular hyperactivity, glandular hypersecretions
      and pain. There are six clinical presentations associated with current occurring
      botulism, each results from absorption of botulinum toxin into the bloodstream.
      AIM: The aim of this review is to summarize the current knowledge on the
      microbiology, epidemiology, vaccine research and clinical management of human
      botulism. CONCLUSIONS: Early diagnosis and management rely on history and
      physical examination. Delay in treatment may allow progression of paralysis,
      protracted hospitalization and deaths of long-term mechanical ventilation and
      intensive care unit care. The clinicians must take this disease into
      consideration of a possible outbreak. Awaiting laboratory confirmation is an
      egregious error, while awareness of the clinical sign and symptoms of botulism is
      critical for early diagnosis. Rapid management and followed public health
      surveillance may greatly alleviate disease severity and decrease mortality rates.

PMID- 21171846
TI  - Type E botulism.
AB  - There are seven known serotypes of botulism, designated A through G; almost all
      human cases of botulism are caused by types A, B, and E. Botulism type E is the
      predominant serotype causing disease associated with native Arctic foods. In the
      circumpolar regions of the world, the coastal soils are rich in botulism type E,
      and consumption of fish and marine animals in these areas are the sources of
      clusters of botulism. Unlike spores of type A and B, botulism type E can
      withstand freezing down to 3.5 degrees C. Alaskan native fermentation of fish
      heads, fish eggs, and beaver tail allow proper anaerobic conditions for botulinum
      toxin to be elaborated from Clostridium botulinum. The consumption of whale meat,
      "muktuk" has also been associated with outbreaks of botulism in Alaska and the
      Canadian Arctic. Elsewhere in the Arctic regions, type E botulism has been
      associated with Norwegian "rakfisk" prepared by a process similar to fermented
      Alaskan foods. Outbreaks in Egypt with the salted gray mullet "faseikh", in
      Israel and New York linked to salted uneviscerated whitefish "kapchunka", in Iran
      from eating "ashbal" an uncooked salmon, and in Japan with "izushi" a traditional
      fermented fish preserved in rice have occurred. Importation of vacuum-packed
      whitefish from Alaska and Canada has also been associated with sporadic cases of
      botulism type E in Europe. In March 2010, the Center for Disease Control and
      Prevention released the heptavalent antitoxin (H-BAT) for use in the USA, under
      an Investigational New Drug program, as the preferred treatment for food-borne
      botulism, including type E, which had not been covered by the bivalent antitoxin,
      the prior approved antitoxin product in the USA.

PMID- 21171847
TI  - Pharmacokinetic-pharmacodynamic modeling in overdose patients - is it worth the
      trouble?

PMID- 21171848
TI  - Clinical profile and outcome of patients hospitalized with dimethyl and diethyl
      organophosphate poisoning.
AB  - The two major classes of organophosphate compounds, dimethyl and diethyl
      organophosphates, have different toxicokinetic properties. This study evaluated
      the clinical profile and outcomes in patients admitted with poisoning with these
      two classes of organophosphates. METHODS: This retrospective study spanned 6
      years (2002-2007). Patients were treated with atropine and supportive care
      including ventilation, as required, and followed up until death or hospital
      discharge. Oximes were not administered. Of the 422 charts retrieved, 396
      fulfilled inclusion criteria. Data on the clinical profile, ventilation, length
      of hospital stay, incidence of intermediate syndrome and mortality were
      extracted. RESULTS: The mean (+/- standard deviation) age was 31.4 +/- 12.7 years
      with a male preponderance (2.6:1). The median (interquartile range (IQR))
      admission pseudocholinesterase level of 317 (222-635) U/L indicated significant
      inhibition of cholinesterase activity. The median lag-time to presentation to our
      hospital was 5 (IQR 3-8.5) hours. Oximes were administered at a primary center in
      33 patients (8.3%). Dimethyl organophosphate was ingested by 141 patients,
      diethyl organophosphate by 108, S-alkyl organophosphate by 2, and an un
      identified organophosphate by 145 patients. Ventilation was required in 260
      patients (65.7%); the median duration of ventilation being 7.5 (IQR 3-12) days.
      Overall mortality was 13.1%. There was a significant difference between dimethyl
      and diethyl organophosphate compounds in ventilatory requirement (76% vs. 56%,
      adjusted odds ratio (OR) 2.37, 95% CI 1.01-5.57, p=0.047), duration of
      ventilation (11 (4-15) vs. 5 (2-9) days, adjusted OR 1.12, 95%CI 1.04-1.21,
      p=0.002) and incidence of intermediate syndrome (72/125 (58%) vs. 24/92 (26%),
      adjusted OR 2.84, 95%CI 1.38-5.86, p=0.004). Mortality was similar in the two
      groups (20/141 (14%) vs. 7/108 (6%), dimethyl vs. diethyl organophosphate,
      adjusted OR 1.29, 95%CI 0.43-3.94, p=0.65). CONCLUSIONS: Patients admitted with
      dimethyl organophosphate poisoning have a worse outcome compared with diethyl
      organophosphate poisoning for clinically relevant patient outcomes.

PMID- 21171849
TI  - Case series of individuals with analytically confirmed acute mephedrone toxicity.
AB  - CONTEXT: Previous reports of acute toxicity/harm associated with mephedrone use
      have been based on self-reported mephedrone use; toxicological screening has not
      been undertaken in these cases to determine whether mephedrone has been used.
      OBJECTIVE: To report the first case series of analytically confirmed mephedrone
      related acute toxicity. MATERIALS AND METHODS: Serum samples were collected from
      individuals presenting to an emergency department (ED) with acute toxicity
      related to self-reported mephedrone use. Toxicological analysis, by gas
      chromatography coupled with mass-spectrometry and liquid chromatography with
      tandem mass-spectrometry was performed to qualitatively confirm mephedrone use.
      Symptoms/signs of acute mephedrone toxicity and basic physiological parameters
      were extracted from the routine ED records. RESULTS: Acute mephedrone-related
      toxicity was analytically confirmed in seven male patients; the mean +/- SD age
      was 24.6 +/- 6.5 years (range 16-36 years). Agitation (four patients) was the
      most common symptom/sign reported; other common symptoms/signs included:
      palpitations (two patients); chest pain (two patients); self-limiting pre
      hospital seizures (one patient) and headaches (one patient). The mean heart rate
      was 109.1 +/- 21.8 (range 80-140) beats per minute; one patient had a "severe"
      tachycardia (heart rate of >= 140 bpm). The mean systolic blood pressure was
      153.0 +/- 39.6 (range 110-210) mmHg; three patients had clinically significant
      hypertension (systolic blood pressure >= 160 mmHg). DISCUSSION: These
      analytically confirmed acute mephedrone toxicity presentations had clinical
      features of toxicity consistent with an acute sympathomimetic toxidrome (e.g.
      hypertension, tachycardia and agitation). These findings are similar to the
      pattern of toxicity seen with other sympathomimetic recreational drugs such as
      3,4-Methylenedioxymethamphetamine (MDMA) and cocaine. CONCLUSION: The process for
      determining whether a novel psychoactive substance should be controlled often
      relies on demonstrated/proven acute harm associated with its use. It is important
      that clinical toxicologists undertake appropriate biological sampling and
      toxicological analyses in suspected cases of "novel psychoactive drug" toxicity.
      This will ensure that both clinicians and legislative authorities are informed of
      the confirmed pattern of toxicity associated with these drugs.

PMID- 21171850
TI  - Pesticide poisonings at a tertiary children's hospital in South Africa: an
      increasing problem.
AB  - CONTEXT: Exposure of children to pesticides and overt poisoning are an
      increasingly important problem in South Africa. OBJECTIVE: This study describes
      the profile of acute paediatric pesticide exposures and poisonings presenting to
      Red Cross War Memorial Children's Hospital (RCWMCH) in Cape Town South Africa
      from 2003 to 2008, identifies those poisonings due to illicit pesticides sold on
      the streets ("street pesticides") and assesses the number of incidents in which
      the statutory requirement of notification to the local health authority is met.
      Methods. Cases were identified by review of the RCWMCH case and notification
      records and the local health authority notification records. RESULTS: There were
      306 patients with 311 incidents of acute pesticide exposure or poisoning. This
      represents 11% of all paediatric exposures and poisonings (N=2868) seen over the
      6-year period. The number of pesticide incidents increased annually. Two hundred
      seventy-eight (91%) children were under 6 years old and 164 (54%) were males. Two
      hundred seventeen (70%) patients came from six socio economically diverse suburbs
      in the Cape Town Metropole, each of which ranges from informal settlements with
      extreme poverty to formal housing with lower to middle class populations. There
      was a summer predominance of acute pesticide exposures and poisonings. The
      commonest group of pesticides were 203 cholinergics (includes organophosphates
      and carbamates), 35 anticoagulants and 45 unknowns. One hundred incidents were
      classified as exposures as they were asymptomatic. Two hundred eleven symptomatic
      incidents, termed pesticide poisonings, required admission; 121 to High Care or
      Intensive Care Unit (ICU). The median length of stay in hospital was 3 days
      (range 0-52). There were 6 (2%) deaths. The large group of cholinergic exposures
      and poisonings (203) required 195 (96%) admissions; 120 (59%) to High Care or
      ICU. Of the 44 "street pesticide" exposures and poisonings, 33 were cholinergic
      poisonings and 21 required High Care or ICU. Eighty-seven (41%) of 211 poisonings
      requiring notification were recorded at the local health authority; all were
      instances of cholinergic poisoning. CONCLUSION: The increasing number and the
      morbidity and mortality of acute paediatric pesticide exposure and poisoning is
      of great concern. Furthermore, the magnitude of the problem is masked by
      inadequate notification with the relevant health authorities.

PMID- 21171851
TI  - Prevalence of anticoagulant rodenticide poisoning in humans and animals in France
      and substances involved.
AB  - INTRODUCTION: Anticoagulant rodenticides have been used for over 50 years to
      control rodent populations. Since their first introduction, resistance developed
      in rodents, and second-generation products, more active but also more toxic, have
      been marketed. These compounds are currently being reviewed under European
      Regulations. METHODS: The purpose of this work is to describe anticoagulant
      poisoning based on retrospective data from French human and animal poison control
      centers. Cases from 2004 to 2007 were collected. RESULTS: Overall, the proportion
      of anticoagulant exposure reported to the Lyon poison control center appeared
      very limited and mostly occurred in young children, with no or very limited
      clinical severity. Some cases also occurred after intentional use of
      anticoagulants in adults. Circumstances of exposure are predominantly accidental
      in man (77%). In animals, both domestic and wild species, anticoagulant exposure
      seems more common, and often more accompanied by clinical signs. Among domestic
      species, dogs represent over 60% of the cases: in wildlife hares and rabbits
      account for almost 50% of the submitted cases, followed by predators and
      scavengers. CONCLUSION: Rodenticides involved are representative of the market
      share of anticoagulants, for human and domestic animal exposures. In wildlife,
      bromadiolone and chlorophacinone are by far the most important products, being
      the only ones registered for field use. There is no report of mortality in the
      human data, and less than 1% of all exposure cases in domestic animals were
      fatal.

PMID- 21171852
TI  - Severe systemic intoxication following triclopyr-TEA ingestion.
AB  - We report a case of triclopyr ingestion, a herbicide that acts via the auxin
      system in plants. It is classified as low-toxicity herbicide. The patient
      ingested this product and developed metabolic acidosis and coma with
      cardiovascular impairment. Echocardiography and elevated Troponin T and CK MB
      with prolongation of QTc suggested direct myocardial toxicity. The patient was
      extubated 57 h after ingestion, and he recovered completely. This case
      illustrates the potential acute toxicity of this agent in humans.

PMID- 21171853
TI  - Status epilepticus and wide-complex tachycardia secondary to diphenhydramine
      overdose.
AB  - OBJECTIVE: Diphenhydramine is an H1 histamine antagonist that is commonly used
      for allergic reactions, colds and cough, and as a sleep aid. In addition to
      anticholinergic and antihistaminergic effects, sodium channel blockade becomes
      evident following diphenhydramine overdose. While seizures may occur following
      overdose of a diphenhydramine, status epilepticus is distinctly uncommon. We
      report a case with both status epilepticus and wide-complex dysrhythmias
      following an intentional diphenhydramine overdose. CASE REPORT: A 36-year-old
      woman with a medical history of hypothyroidism on levothyroxine was brought to
      the emergency department with active seizures by emergency medical services after
      what was later determined to be a diphenhydramine overdose. One hour after an
      argument with her husband he found her lethargic in a locked room. Initial vital
      signs were: blood pressure, 90/55 mmHg; heart rate, 160 beats/min; respiratory
      rate 18 breaths/min; room air oxygen saturation, 99%; temperature, 99.8 degrees
      F; rapid point-of-care glucose, 130 mg/dL. The generalized seizures continued for
      duration of 30 min, despite the intravenous administration of 8 mg of lorazepam.
      The patient underwent endotracheal intubation and a propofol infusion terminated
      her seizures. An electrocardiogram after the status was terminated which revealed
      a wide-complex tachycardia with QRS duration of 127 ms. The QRS narrowed after
      200 mEq of intravenous sodium bicarbonate was administrated. The patient was
      neurologically intact upon extubation on hospital day 2. The serum
      diphenhydramine concentration drawn on arrival to the ED was 1200 ng/mL (9-120
      ng/mL); a tricyclic screen was negative. DISCUSSION: While seizures and sodium
      channel blockade are recognized complications of diphenhydramine toxicity,
      reported cases of status epilepticus from diphenhydramine overdose are rare.
      Elements of the patient's presentation were similar to a tricyclic overdose and
      management required aggressive control of her seizures, sodium bicarbonate
      therapy, and recognizing that physostigmine was contraindicated due to wide
      complex tachycardia. CONCLUSIONS: Diphenhydramine overdose may cause status
      epilepticus and wide-complex tachycardia. Management should focus on antidotal
      therapy with sodium bicarbonate and supportive neurological management with
      appropriate anticonvulsants and airway protection if clinically indicated.

PMID- 21171854
TI  - Accidental poisoning with Veratrum album mistaken for wild garlic (Allium
      ursinum).
AB  - INTRODUCTION: Veratrum album (white or false hellebore) is a poisonous plant
      containing steroidal alkaloids that cause nausea, vomiting, headache, visual
      disturbances, paresthesia, dizziness, bradycardia, atrioventricular block,
      hypotension, and syncope. It is regularly mistaken for Gentiana lutea (yellow
      gentian). We report accidental poisoning with V. album mistaken for Allium
      ursinum (wild garlic), a wild plant used in soups and salads in Central Europe.
      CASE SERIES: Four adults (24-45 years) accidentally ingested V. album mistaken
      for A. ursinum in self-prepared salads and soups. Within 15-30 min of ingestion
      they developed nausea, vomiting, and abdominal pain. At the same time dizziness,
      tingling, dimmed and jumping vision, transient blindness, and confusion appeared.
      On arrival at the ED, all patients had sinus bradycardia and hypotension.
      Following treatment the patients were discharged well 24-48 h after ingestion.
      CONCLUSION: In patients presenting with gastrointestinal, neurological, and
      cardiovascular symptoms a history of wild plant ingestion suggests possible
      poisoning with V. album mistaken for wild garlic.

PMID- 21171856
TI  - Life-threatening hyponatremia after krait bite envenoming - a new syndrome.
AB  - INTRODUCTION: Bites by kraits are a major cause of snake bite death in South
      Asia, mainly because of their venom is paralytic causing respiratory failure. We
      describe another life-threatening effect of the venom of some Bungarus species.
      CASE REPORT: We report the death of a young woman due to severe hyponatremia
      induced brain damage after envenoming attributed to a Bungarus multicinctus. Her
      serum sodium of 137 mmol/l on admission dropped to 104 mmol/l within 48 h. The
      patient suddenly deteriorated with seizures and coma and showed signs of severe
      cerebral edema. The osmolality and sodium concentration in her urine were high.
      She died 18 days after the bite. DISCUSSION: Since this case, a retrospective
      study and a prospective trial have confirmed the high risk of hyponatremia after
      envenoming by B. multicinctus. In addition, a recent study in southern Vietnam
      has shown that envenoming by the Malayan krait (Bungarus candidus) also commonly
      causes profound hyponatremia. CONCLUSION: Hyponatremia is a potential serious
      complication in patients envenomed by B. multicinctus or B. candidus, and
      appropriate monitoring and management is necessary.

PMID- 21171855
TI  - Survival after hypocalcemia, hypomagnesemia, hypokalemia and cardiac arrest
      following mild hydrofluoric acid burn.
AB  - BACKGROUND: Although hydrofluoric (HF) acid burns may cause extensive tissue
      damage, severe systemic toxicity is not common after mild dermal exposure. CASE:
      A 36-year-old worker suffered a first-degree burn of 3% of his total body surface
      area as a result of being splashed on the right thigh with 20% HF acid. Immediate
      irrigation and topical use of calcium gluconate gel prevented local injury.
      However, the patient developed hypocalcemia and hypomagnesemia, hypokalemia,
      bradycardia, and eventually had asystole at 16 h post-exposure, which were
      unusual findings. He was successfully resuscitated by administration of calcium,
      magnesium, and potassium. CONCLUSION: This report highlights a late risk of HF
      acid dermal exposure.

PMID- 21171858
TI  - "Massive acetaminophen ingestion with early metabolic acidosis and coma:
      treatment with iv nac and continuous venovenous hemodiafiltration" by Wiegand et
      al., Clin Toxicol (Phila) 48:156-159.

PMID- 21171859
TI  - Nosocomial scorpion envenomation: an unusual mode of scorpion sting.

PMID- 21171860
TI  - Sinusoidal obstruction syndrome associated with the ingestion of gynura root.

PMID- 21171861
TI  - A new generation of serotype chimeric infectivity-enhanced conditionally
      replicative adenovirals: the safety profile of ad5/3-Delta24 in advance of a
      phase I clinical trial in ovarian cancer patients.
AB  - Conditionally replicative adenoviral (CRAd) virotherapy represents a promising
      therapeutic approach for cancer. We have demonstrated that a serotype chimeric
      adenoviral 5/3 fiber-knob modification achieves enhanced ovarian cancer
      infectivity, conditional replication, and oncolytic activity. This study
      evaluated the safety of intraperitoneal (IP) Ad5/3-Delta24 in advance of a phase
      I clinical trial in gynecologic cancers. Syrian hamster cohorts were treated with
      IP Ad5/3-Delta24 or control buffer for 3 consecutive days and euthanized on study
      days 8, 17, 57, and 89. Blood and tissue samples were harvested from each animal.
      For biodistribution studies, presence and quantitation of viral levels within
      samples were determined via quantitative polymerase chain reaction. For safety
      studies, animals were assessed for adverse vector-related tissue or laboratory
      effects. In the biodistribution study, low levels of Ad5/3-Delta24 DNA were noted
      outside of the abdominal cavity. Viral DNA levels in tissues obtained from the
      peritoneal cavity peaked at day 8 and declined thereafter. In the safety study,
      no specific histopathologic changes were attributable to virus administration.
      Hematologic findings noted in the 1 * 10(11) viral particles (vp)/dose group on
      Days 4 and/or 8 were indicative of an Ad5/3-Delta24-specific generalized
      inflammatory response; these findings resolved by day 56. The no observable
      adverse effect level was determined to be 1 * 10(10) vp/dose. This study
      elucidates the safety profile of IP administration of the serotype chimeric
      infectivity-enhanced CRAd, Ad5/3-Delta24, and provides guidance for a planned
      phase I trial for patients with recurrent gynecologic cancers.

PMID- 21171862
TI  - Immunomodulatory effects of intravenous immunoglobulins (IVIGs) in HIV-1 disease:
      a systematic review.
AB  - Intravenous immunoglobulins (IVIGs) are generally used as replacement therapy for
      humoral immunodeficiencies. In consideration of their immune-modulating
      properties, they are also employed as "immune-modulating/anti-inflammatory"
      treatment in different clinical conditions. In HIV-1 infection, an increased
      incidence of autoimmune and auto-inflammatory manifestations has been described,
      probably as a consequence of the chronic immune activation associated with the
      disease. The initial use in the treatment of bacterial infections in children
      with HIV/AIDS has been replaced by the treatment, in combination with
      antiretroviral therapy, of these autoimmune/inflammatory conditions. We review
      the results obtained with IVIGs therapy in these HIV-1-associated clinical
      manifestations.

PMID- 21171863
TI  - Optimization of primer-specific filter metrics for the assessment of
      mitochondrial DNA sequence data.
AB  - Filter metrics are used as a quick assessment of sequence trace files in order to
      sort data into different categories (i.e. high quality, review, and low quality)
      without human intervention. The filter metrics consist of two numerical
      parameters for sequence quality assessment: trace score (TS) and contiguous read
      length (CRL). Primer-specific settings for the TS and CRL were established using
      a calibration dataset of 2817 traces and validated using a concordance dataset of
      5617 traces. Prior to optimization, 57% of the traces required manual review
      before import into a sequence analysis program, whereas after optimization only
      28% of the traces required manual review. After optimization of primer-specific
      filter metrics for mitochondrial DNA sequence data, an overall reduction of
      review of trace files translates into increased throughput of data analysis and
      decreased time required for manual review.

PMID- 21171864
TI  - Barcoding, types and the Hirudo files: using information content to critically
      evaluate the identity of DNA barcodes.
AB  - Species identifications based on DNA barcoding rely on the correct identity of
      previously barcoded specimens, but little attention has been given to whether
      deposited barcodes include correspondence to the species' name-bearing type. The
      information content associated with COX1 sequences in the two most commonly used
      repositories of barcodes, GenBank and the Barcode of Life Data System (BOLD), is
      often insufficient for subsequent evaluation of the robustness of the
      identification procedure. We argue that DNA barcoding and taxonomy alike will
      benefit from more information content in the annotations of barcoded specimens as
      this will allow for validation and re-evaluation of the initial specimen
      identification. The aim should be to closely connect specimens from which
      reference barcodes are generated with the holotype through straight-forward
      taxonomy, and geographical and genetic correlations. Annotated information should
      also include voucher specimens and collector/identifier information. We examine
      two case studies based on empirical data, in which barcoding and taxonomy benefit
      from increased information content. On the basis of data from the first case
      study, we designate a barcoded neotype of the European medicinal leech, Hirudo
      medicinalis, on morphological and geographical grounds.

PMID- 21171865
TI  - After 7 years and 1000 citations: comparative assessment of the DNA barcoding and
      the DNA taxonomy proposals for taxonomists and non-taxonomists.
AB  - In 2003, two different approaches-DNA taxonomy and DNA barcoding-were
      simultaneously proposed to overcome some of the perceived intrinsic weaknesses of
      the traditional morphology-based taxonomical system, and to help non-taxonomists
      to resolve their crucial need for accurate and rapid species identification
      tools. After 7 years, it seems unlikely that a completely new taxonomical system
      based on molecular characters only (DNA taxonomy) will develop in the future. It
      is more likely that both morphological and molecular data will be simultaneously
      analyzed, developing what has been coined as "integrative taxonomy". Concerning
      DNA barcoding, it is now clear that it does not focus on building a tree-of-life
      nor to perform DNA taxonomy, but rather to produce a universal molecular
      identification key based on strong taxonomic knowledge that is collated in the
      barcode reference library. The indisputable success of the DNA barcoding project
      is chiefly due to the fact that DNA barcoding standards considerably enhance
      current practices in the molecular identification field, and standardization
      offers virtually endless applications for various users.

PMID- 21171866
TI  - Wolbachia infection and mitochondrial diversity in the canine heartworm
      (Dirofilaria immitis).
AB  - BACKGROUND AND AIMS: Many species of filarial nematodes are infected with
      Wolbachia pipientis, a maternally inherited endosymbiont. In addition to
      manipulating host reproduction, these bacteria also affect the evolution of the
      mitochondrial DNA with which they are transmitted. Selective sweeps can establish
      a single mitochondrial lineage within a Wolbachia-infected population and purge
      genetic diversity. While this phenomenon has been studied in insect model
      systems, it has not been thoroughly examined in a filarial nematode. MATERIALS
      AND METHODS: Patterns of mitochondrial diversity were examined in Dirofilaria
      immitis, a Wolbachia-infected species. RESULTS: The levels of genetic diversity
      observed in canine heartworm were much lower than those in related species not
      known to be hosts of Wolbachia. CONCLUSION: RESULTS suggest that a maternally
      inherited endosymbiont can depress mitochondrial diversity in a filarial host.

PMID- 21171867
TI  - Imatinib trough levels in chronic myelogenous leukemia: does one dose fit all?

PMID- 21171868
TI  - Romiplostim for chronic lymphocytic leukemia-associated immune thrombocytopenia.

PMID- 21171869
TI  - Translation control is critical during acute and chronic stages of toxoplasmosis
      infection.

PMID- 21171870
TI  - The urgent need to develop new drugs and tools for the treatment of Chagas
      disease.

PMID- 21171871
TI  - UN releases new figures on HIV/AIDS epidemic.

PMID- 21171873
TI  - Broadening sexual health horizons in Georgia.
AB  - The 25th International Union against Sexually Transmitted Infection (IUSTI)
      Europe conference was the first to be held in the former Soviet Union. The
      location of Tblisi, Georgia, proved to be a tremendous choice and the conference
      title 'Broadening your Horizons' appropriately referred to the scientific
      content, as well as to over 350 conference delegates experiencing Georgia and
      wonderful Georgian hospitality for the first time.

PMID- 21171872
TI  - Miconazole mucoadhesive tablet for oropharyngeal candidiasis.
AB  - Oropharyngeal candidiasis is a commonly encountered problem in daily clinical
      practice. Topical therapies for oropharyngeal candidiasis are considered
      preferable to systemic therapies in most patient populations. However,
      traditional topical therapies have limitations including short contact time with
      the oral mucosa and the need for multiple doses each day. Miconazole mucoadhesive
      tablet has recently been approved in Europe (Loramyc(r)) and the USA (OravigTM)
      for the treatment of oropharyngeal candidiasis. This tablet adheres to the oral
      mucosa and provides sustained local release of miconazole over a period of
      several hours with just one daily application. This article reviews the
      pharmacology, safety and efficacy of this novel agent.

PMID- 21171874
TI  - Control of hepatitis B in China: prevention and treatment.
AB  - A high rate of chronic HBV infection in China is mainly the result of perinatal
      or early childhood transmission. Therefore, universal vaccination against HBV in
      infants has been very successful in the control of chronic HBV infection, with
      the prevalence of hepatitis B surface antigen decreasing from nearly 10% to
      approximately 7% in the general population. Adoption of Good Clinical Practice
      and proper conduction of well-designed clinical trials on conventional and
      pegylated interferons and nucleos(t)ide analogs have generated important clinical
      data. The publication and promotion of the evidence-based national guidelines
      have greatly improved the standard of clinical practice on the prevention and
      treatment of chronic hepatitis B. The ongoing national key scientific projects on
      the optimization of vaccination strategy and current anti-HBV therapy will yield
      important clinical evidence. Inclusion of conventional and pegylated interferons
      and nucleos(t)ides into the new national reimbursement list will increase the
      availability and affordability of anti-HBV therapies, thereby further decreasing
      the morbidity and mortality associated with chronic HBV infection.

PMID- 21171875
TI  - Respiratory syncytial virus disease: update on treatment and prevention.
AB  - Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory
      tract infections in infants and young children, accounting for more than 100,000
      hospitalizations per year in the USA. The majority of hospitalizations occur in
      infants less than 1 year of age. Worldwide, RSV is associated with an annual
      mortality rate of 160,000-600,000 deaths. Premature infants, and infants with
      congenital heart disease, neuromuscular disease, structural airway abnormalities
      and immunodeficiencies are at increased risk for severe RSV disease. Despite the
      magnitude of RSV disease, treatment remains primarily supportive. Trials of
      bronchodilators, corticosteroids and montelukast have not demonstrated conclusive
      clinical benefit. The antiviral drug ribavirin has demonstrated only marginal
      clinical benefit and is not routinely indicated in treatment of RSV disease.
      Palivizumab is beneficial in prophylaxis for infants at high-risk for severe RSV
      infection although optimal indications based on cost-effectiveness considerations
      have not been defined. Future directions in treatment and prevention of RSV
      infections likely include the second-generation monoclonal antibody motavizumab,
      more potent antiviral compounds and more unique anti-inflammatory agents.
      Vaccination against RSV is in development but not eminent.

PMID- 21171876
TI  - Hantavirus protein interactions regulate cellular functions and signaling
      responses.
AB  - Rodent-borne pathogenic hantaviruses cause two severe and often lethal zoonotic
      diseases: hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus
      cardiopulmonary syndrome (HCPS) in the Americas. Currently, no US FDA-approved
      therapeutics or vaccines are available for HFRS/HCPS. Infections with
      hantaviruses are not lytic, and it is currently not known exactly why infections
      in humans cause disease. A better understanding of how hantaviruses interfere
      with normal cell functions and activation of innate and adaptive immune responses
      might provide clues to future development of specific treatment and/or vaccines
      against hantavirus infection. In this article, the current knowledge regarding
      immune responses observed in patients, hantavirus interference with cellular
      proteins and signaling pathways, and possible approaches in the development of
      therapeutics are discussed.

PMID- 21171877
TI  - Pathogenesis of arenavirus hemorrhagic fevers.
AB  - Viral hemorrhagic fevers (VHFs) caused by arenaviruses belong to the most
      devastating emerging human diseases and represent serious public health problems.
      Arenavirus VHFs in humans are acute diseases characterized by fever and, in
      severe cases, different degrees of hemorrhages associated with a shock syndrome
      in the terminal stage. Over the past years, much has been learned about the
      pathogenesis of arenaviruses at the cellular level, in particular their ability
      to subvert the host cell's innate antiviral defenses. Clinical studies and novel
      animal models have provided important new information about the interaction of
      hemorrhagic arenaviruses with the host's adaptive immune system, in particular
      virus-induced immunosuppression, and have provided the first hints towards an
      understanding of the terminal hemorrhagic shock syndrome. The scope of this
      article is to review our current knowledge on arenavirus VHF pathogenesis with an
      emphasis on recent developments.

PMID- 21171878
TI  - Recommendations and rationale for the treatment of pelvic inflammatory disease.
AB  - Pelvic inflammatory disease (PID) is one of the most common serious infections of
      nonpregnant women of reproductive age. Management of PID is directed at
      containment of infection. Goals of therapy include the resolution of clinical
      symptoms and signs, the eradication of pathogens from the genital tract and the
      prevention of sequelae including infertility, ectopic pregnancy and chronic
      pelvic pain. The choice of an antibiotic regimen used to treat PID relies upon
      the appreciation of the polymicrobial etiology of this ascending infection
      including Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium and
      other lower genital tract endogenous anaerobic and facultative bacteria, many of
      which are associated with bacterial vaginosis. Currently available evidence and
      the CDC treatment recommendations support the use of broad-spectrum antibiotic
      regimens that adequately cover the above named microorganisms. The outpatient
      treatment of mild-to-moderate PID should include tolerated antibiotic regimens
      consisting of an extended-spectrum cephalosporin in conjunction with either
      azithromycin or doxycycline. Clinically severe PID should prompt hospitalization
      and imaging to rule out a tubo-ovarian abscess. Parenteral broad-spectrum
      antibiotic therapy with activity against a polymicrobial flora, particularly Gram
      negative aerobes and anaerobes, should be implemented.

PMID- 21171879
TI  - Biomarkers for pediatric sepsis and septic shock.
AB  - Sepsis is a clinical syndrome defined by physiologic changes indicative of
      systemic inflammation, which are likely attributable to documented or suspected
      infection. Septic shock is the progression of those physiologic changes to the
      extent that delivery of oxygen and metabolic substrate to tissues is compromised.
      Biomarkers have the potential to diagnose, monitor, stratify and predict outcome
      in these syndromes. C-reactive protein is elevated in inflammatory and infectious
      conditions and has long been used as a biomarker indicating infection.
      Procalcitonin has more recently been shown to better distinguish infection from
      inflammation. Newer candidate biomarkers for infection include IL-18 and CD64.
      Lactate facilitates the diagnosis of septic shock and the monitoring of its
      progression. Multiple stratification biomarkers based on genome-wide expression
      profiling are under active investigation and present exciting future
      possibilities.

PMID- 21171880
TI  - Prophylaxis and treatment of infections associated with penetrating traumatic
      injury.
AB  - Accidents or violence can result in penetrating trauma in the adult population.
      Contaminated penetrating foreign bodies introduced at the time of wounding cause
      infection, especially high velocity projectiles, which result in cavitation.
      Surgical debridement reduces potential infection; however, perioperative
      antibiotics are usually indicated owing to studies demonstrating high rates of
      sepsis in the pre-antibiotic era. Trauma-associated pathogens include Gram
      positive, Gram-negative and anaerobic pathogens. Antibiotic resistance is
      increasing, and several recent panels have sought to develop guidelines for
      perioperative prevention and empiric treatment of infection to limit usage and
      reduce selective pressure for resistance. We review infections of the CNS,
      thorax, abdomen and extremities following penetrating trauma injury, as well as
      the data supporting a reasonable antimicrobial approach.

PMID- 21171881
TI  - Overview of antimicrobial therapy in intensive care units.
AB  - In the management of a patient with severe sepsis, it is important to suspect the
      infection early, to collect samples immediately after diagnosis and to promptly
      initiate a broad-spectrum antibiotic treatment. The choice of this empirical
      antimicrobial therapy should be based on host characteristics, site of infection,
      local ecology and pharmacokinetics/pharmacodynamics of antibiotics. In severe
      infection, guidelines recommend the use of a combination of antibiotics. After
      results of cultures are obtained, treatment should be re-evaluated to either de
      escalate or escalate the antibiotic prescription. This is associated with optimal
      costs, decreased incidence of superinfection and minimal development of
      antimicrobial resistance. All these steps should rely on written protocols, and
      the compliance to these protocols should be continuously monitored in order to
      detect violations and implement corrective procedures.

PMID- 21171882
TI  - Diagnosis of acute leptospirosis.
AB  - Leptospirosis is a globally important zoonotic disease and an important public
      health problem in developing countries. Early diagnosis is essential because
      antibiotic treatment is most effective when initiated early in the course of the
      disease. Culture and the microscopic agglutination test are gold standard methods
      for leptospirosis diagnosis; however, they are not useful for early diagnosis.
      Current whole cell-based rapid serological tests have low sensitivity for early
      phase leptospirosis and may have low specificity in highly endemic areas. PCR is
      demonstrably useful for early diagnosis, but it is unavailable in most developing
      countries. Thus, diagnostic methods that not only have higher sensitivity and
      accuracy for early phase leptospirosis but are also widely applicable in
      developing countries remain to be developed. The availability of genome sequences
      and genetic tools of Leptospira spp. will accelerate our understanding of
      Leptospira pathogenesis and provide insights into the development of more
      efficient and accurate diagnostic tests for acute-phase leptospirosis.

PMID- 21171883
TI  - Subarachnoid basal neurocysticercosis: a focus on the most severe form of the
      disease.
AB  - Neurocysticercosis is an endemic disease in Latin America, Asia and Africa with
      growing occurrence in industrialized countries due to the increase in migration
      from low- and middle-income to high-income countries. The most severe clinical
      presentation is when the parasite is located in the subarachnoid space at the
      base of the brain (NCSAB). Aside from its clinical presentation, the severity of
      this form of the disease is due to the difficulties in diagnosis and treatment.
      Although NCSAB frequency is lower than that reported for the parenchymal location
      of the parasite, its clinical relevance must be emphasized. We provide a critical
      review of the central epidemiological, clinical, diagnostic and therapeutic
      features of this particular form of the disease, which is still associated with
      unacceptably high rates of morbidity and mortality.

PMID- 21171885
TI  - Molecular mapping of the new blast resistance genes Pi47 and Pi48 in the durably
      resistant local rice cultivar Xiangzi 3150.
AB  - The indica rice cultivar Xiangzi 3150 (XZ3150) confers a high level of resistance
      to 95% of the isolates of Magnaporthe oryzae (the agent of rice blast disease)
      collected in Hunan Province, China. To identify the resistance (R) gene(s)
      controlling the high level of resistance in this cultivar, we developed 286 F(9)
      recombinant inbred lines (RILs) from a cross between XZ3150 and the highly
      susceptible cultivar CO39. Inoculation of the RILs and an F(2) population from a
      cross between the two cultivars with the avirulent isolate 193-1-1 in the growth
      chamber indicated the presence of two dominant R genes in XZ3150. A linkage map
      with 134 polymorphic simple sequence repeat and single feature polymorphism
      markers was constructed with the genotype data of the 286 RILs. Composite
      interval mapping (CIM) using the results of 193-1-1 inoculation showed that two
      major R genes, designated Pi47 and Pi48, were located between RM206 and RM224 on
      chromosome 11, and between RM5364 and RM7102 on chromosome 12, respectively.
      Interestingly, the CIM analysis of the four resistant components of the RILs to
      the field blast population revealed that Pi47 and Pi48 were also the major
      genetic factors responsible for the field resistance in XZ3150. The DNA markers
      linked to the new R genes identified in this study should be useful for further
      fine mapping, gene cloning, and marker-aided breeding of blast-resistant rice
      cultivars.

PMID- 21171887
TI  - Decline as a disease category: is it helpful?
AB  - Many, but not all, forest pathologists use "decline" to describe forest tree
      diseases of complex etiology. We contend that this distinction from abiotic or
      biotic diseases is completely arbitrary, has caused undue confusion, and provides
      no practical insights for forest managers. All diseases are complex and can be
      characterized within the conceptual framework of the disease triangle. Why do we
      use a simple label ("decline") to describe disease situations of complex abiotic
      and biotic origin when we need to know which damaging agents are present, whether
      the environment is conducive for disease progression, and host susceptibility
      over time to understand the origins and management of disease? We propose that
      forest pathologists discontinue the use of "decline" as a distinct category of
      disease. Furthermore, we suggest that new diseases should be named based on the
      affected host, characteristic symptom, and, once known, major determinant. We
      believe that clearer communication in describing complex diseases is a
      prerequisite to finding effective management options.

PMID- 21171886
TI  - Analysis of the epitope structure of Plum pox virus coat protein.
AB  - Typing of the particular Plum pox virus (PPV) strain responsible in an outbreak
      has important practical implications and is frequently performed using strain
      specific monoclonal antibodies (MAbs). Analysis in Western blots of the
      reactivity of 24 MAbs to a 112-amino-acid N-terminal fragment of the PPV coat
      protein (CP) expressed in Escherichia coli showed that 21 of the 24 MAbs
      recognized linear or denaturation-insensitive epitopes. A series of eight C
      truncated CP fragments allowed the mapping of the epitopes recognized by the
      MAbs. In all, 14 of them reacted to the N-terminal hypervariable region, defining
      a minimum of six epitopes, while 7 reacted to the beginning of the core region,
      defining a minimum of three epitopes. Sequence comparisons allowed the more
      precise positioning of regions recognized by several MAbs, including those
      recognized by the 5B-IVIA universal MAb (amino acids 94 to 100) and by the 4DG5
      and 4DG11 D serogroup-specific MAbs (amino acids 43 to 64). A similar approach
      coupled with infectious cDNA clone mutagenesis showed that a V74T mutation in the
      N-terminus of the CP abolished the binding of the M serogroup-specific AL MAb.
      Taken together, these results provide a detailed positioning of the epitopes
      recognized by the most widely used PPV detection and typing MAbs.

PMID- 21171888
TI  - Multigenic system controlling viral systemic infection determined by the
      interactions between Cucumber mosaic virus genes and quantitative trait loci of
      soybean cultivars.
AB  - Soybean 'Harosoy' is resistant to Cucumber mosaic virus soybean strain C (CMV-SC)
      and susceptible to CMV-S strain D (CMV-SD). Using enzyme-linked immunosorbent
      assay and Northern hybridization, we characterized the Harosoy resistance and
      found that CMV-SC did not spread systemically but was restricted to the
      inoculated leaves in Harosoy. Harosoy resistance was not controlled by either a
      dominant or recessive single gene. To dissect this system controlling long
      distance movement of CMV in soybean, we constructed infectious cDNA clones of CMV
      SC and CMV-SD. Using these constructs and the chimeric RNAs, we demonstrated that
      two viral components were required for systemic infection by the virus. The
      region including the entire 2b gene and the 5' region of RNA3 (mainly the 5'
      untranslated region) together were required. By quantitative trait locus (QTL)
      analysis using an F(2) population and the F(3) families derived from Harosoy and
      susceptible 'Nemashirazu', we also showed that at least three QTLs affected
      systemic infection of CMV in soybean. Our study on Harosoy resistance to CMV-SC
      revealed an interesting mechanism, in which multiple host and viral genes
      coordinately controlled viral systemic infection.

PMID- 21171889
TI  - Effects of jasmonic acid, ethylene, and salicylic acid signaling on the
      rhizosphere bacterial community of Arabidopsis thaliana.
AB  - Systemically induced resistance is a promising strategy to control plant
      diseases, as it affects numerous pathogens. However, since induced resistance
      reduces one or both growth and activity of plant pathogens, the indigenous
      microflora may also be affected by an enhanced defensive state of the plant. The
      aim of this study was to elucidate how much the bacterial rhizosphere microflora
      of Arabidopsis is affected by induced systemic resistance (ISR) or systemic
      acquired resistance (SAR). Therefore, the bacterial microflora of wild-type
      plants and plants affected in their defense signaling was compared. Additionally,
      ISR was induced by application of methyl jasmonate and SAR by treatment with
      salicylic acid or benzothiadiazole. As a comparative model, we also used wild
      type and ethylene-insensitive tobacco. Some of the Arabidopsis genotypes affected
      in defense signaling showed altered numbers of culturable bacteria in their
      rhizospheres; however, effects were dependent on soil type. Effects of plant
      genotype on rhizosphere bacterial community structure could not be related to
      plant defense because chemical activation of ISR or SAR had no significant
      effects on density and structure of the rhizosphere bacterial community. These
      findings support the notion that control of plant diseases by elicitation of
      systemic resistance will not significantly affect the resident soil bacterial
      microflora.

PMID- 21171890
TI  - Gene encoding a c-type cyclin in Mycosphaerella graminicola is involved in aerial
      mycelium formation, filamentous growth, hyphal swelling, melanin biosynthesis,
      stress response, and pathogenicity.
AB  - Mycosphaerella graminicola is an important wheat pathogen causing Septoria
      tritici blotch. To date, an efficient strategy to control M. graminicola has not
      been developed. More significantly, we have a limited understanding of the
      molecular mechanisms of M. graminicola pathogenicity. In this study, we attempted
      to characterize an MCC1-encoding c-type cyclin, a gene homologous to FCC1 in
      Fusarium verticillioides. Four independent MCC1 knock-out mutants were generated
      via Agrobacterium tumefaciens-mediated transformation. All of the MCC1 mutants
      showed consistent multiple phenotypes. Significant reductions in radial growth on
      potato dextrose agar (PDA) were observed in all of the MCC1 mutants. In addition,
      MCC1 gene-deletion mutants produced less aerial mycelium on PDA, showed delayed
      filamentous growth, had unusual hyphal swellings, produced more melanin, showed
      an increase in their stress tolerance response, and were reduced significantly in
      pathogenicity. These results indicate that the MCC1 gene is involved in multiple
      signaling pathways, including those involved in pathogenicity in M. graminicola.

PMID- 21171891
TI  - Pectin methylesterase is induced in Arabidopsis upon infection and is necessary
      for a successful colonization by necrotrophic pathogens.
AB  - The ability of bacterial or fungal necrotrophs to produce enzymes capable of
      degrading pectin is often related to a successful initiation of the infective
      process. Pectin is synthesized in a highly methylesterified form and is
      subsequently de-esterified in muro by pectin methylesterase. De-esterification
      makes pectin more susceptible to the degradation by pectic enzymes such as
      endopolygalacturonases (endoPG) and pectate lyases secreted by necrotrophic
      pathogens during the first stages of infection. We show that, upon infection,
      Pectobacterium carotovorum and Botrytis cinerea induce in Arabidopsis a rapid
      expression of AtPME3 that acts as a susceptibility factor and is required for the
      initial colonization of the host tissue.

PMID- 21171892
TI  - Linked, if not the same, Mi-1 homologues confer resistance to tomato powdery
      mildew and root-knot nematodes.
AB  - On the short arm of tomato chromosome 6, a cluster of disease resistance (R)
      genes have evolved harboring the Mi-1 and Cf genes. The Mi-1 gene confers
      resistance to root-knot nematodes, aphids, and whiteflies. Previously, we mapped
      two genes, Ol-4 and Ol-6, for resistance to tomato powdery mildew in this
      cluster. The aim of this study was to investigate whether Ol-4 and Ol-6 are
      homologues of the R genes located in this cluster. We show that near-isogenic
      lines (NIL) harboring Ol-4 (NIL-Ol-4) and Ol-6 (NIL-Ol-6) are also resistant to
      nematodes and aphids. Genetically, the resistance to nematodes cosegregates with
      Ol-4 and Ol-6, which are further fine-mapped to the Mi-1 cluster. We provide
      evidence that the composition of Mi-1 homologues in NIL-Ol-4 and NIL-Ol-6 is
      different from other nematode-resistant tomato lines, Motelle and VFNT, harboring
      the Mi-1 gene. Furthermore, we demonstrate that the resistance to both nematodes
      and tomato powdery mildew in these two NIL is governed by linked (if not the
      same) Mi-1 homologues in the Mi-1 gene cluster. Finally, we discuss how Solanum
      crops exploit Mi-1 homologues to defend themselves against distinct pathogens.

PMID- 21171893
TI  - Identification and characterization of 2'-deoxyuridine from the supernatant of
      conidial suspensions of rice blast fungus as an infection-promoting factor in
      rice plants.
AB  - We previously detected infection-promoting activity in the supernatant of the
      conidial suspension (SCS) of the rice blast fungus. In the present study, a
      molecule carrying the activity was purified and identified as 2'-deoxyuridine
      (dU). The infection-promoting activity of dU was strictly dependent on its
      chemical structure and displayed characteristics consistent with those of the
      SCS. Notably, the activity of dU was exclusively detected during interactions
      between rice and virulent isolates of the fungus, the number of susceptible
      lesions in leaf blades was increased by dU, and nonhost resistance in rice plants
      was not affected by treatment with dU. In addition, the expression of pathogensis
      related genes, accumulation of H(2)O(2), and production of phytoalexins in rice
      in response to inoculation with virulent fungal isolates was not suppressed by
      dU. The infection-promoting activity of dU was not accompanied by elevated levels
      of endogenous abscissic acid, which is known to modify plant-pathogen
      interactions, and was not detected in interactions between oat plants and a
      virulent oat blast fungus isolate. Taken together, these results demonstrate that
      dU is a novel infection-promoting factor that acts specifically during compatible
      interactions between rice plants and rice blast fungus in a mode distinct from
      that of toxins and suppressors.

PMID- 21171894
TI  - Apixaban inhibition of factor Xa: Microscopic rate constants and inhibition
      mechanism in purified protein systems and in human plasma.
AB  - Apixaban is a potent, direct, selective, and orally active inhibitor of
      coagulation factor Xa. Rate constants for apixaban binding to free and
      prothrombinase-bound factor Xa were measured using multiple techniques. The
      inhibition mechanism was determined in purified systems and in a plasma
      prothrombin clotting time assay. Apixaban inhibits factor Xa with a K(i) of 0.25
      nM at 37 degrees C, an association rate constant of approximately 20 MUM(-1) s(
      1), and a dissociation half-life of 1-2 min. Under physiological conditions
      apixaban exhibits mixed-type inhibition and maintains high factor Xa affinity
      with a K(i) of 0.62 nM and association rate constant of 12 MUM(-1) s(-1) for
      prothrombinase, and a K(i) of 1.7 nM and association rate constant of 4 MUM(-1)
      s(-1) for the prothrombinase:prothrombin complex. Experiments in prothrombin
      depleted human plasma showed that the mechanism and kinetics of inhibition are
      maintained in plasma. The mechanistic detail derived from these experiments can
      be used to understand and interpret the pharmacodynamic action of apixaban.

PMID- 21171895
TI  - Thiazolidin-4-one and hydrazone derivatives of capric acid as possible anti
      inflammatory, analgesic and hydrogen peroxide-scavenging agents.
AB  - Starting from capric acid, hydrazone and thiazolidin-4-one derivatives have been
      synthesized in the present investigation. Decanoic acid hydrazide was reacted
      appropriately to yield hydrazones, which were then cyclized to yield the
      corresponding thiazolidin-4-ones. The structures of the newly synthesized
      compounds were confirmed by analytical and spectral methods. Anti-inflammatory,
      analgesic, and hydrogen peroxide-scavenging activity of the title compounds were
      evaluated. Among synthesized compounds, 2-hydroxyphenyl thiazolidinone with
      44.90% inhibition of inflammation was the most potent anti-inflammatory agent.
      Similarly, 4-methoxybenzylidine hydrazide with 64.90% inhibition of writhing was
      observed to be the most potent analgesic agent of the synthesized compounds. All
      the synthesized compounds exhibited potent hydrogen peroxide-scavenging activity.

PMID- 21171896
TI  - Prediction of the relationship between the structural features of andrographolide
      derivatives and alpha-glucosidase inhibitory activity: a quantitative structure
      activity relationship (QSAR) study.
AB  - In order to predict the structural features responsible for alpha-glucosidase
      inhibitory activity, a quantitative structure-activity relationship (QSAR)
      analysis was performed on a series of andrographolide derivatives. To determine
      the quantitative relationship for the statistically significant models in terms
      of r (>0.8), F (99%) and Q(2) (>0.71) values were selected. The promising results
      we obtained could be used to predict the structural requirements for the
      inhibition of alpha-glucosidase activity. The models developed included:
      subdivided surface area, adjacency, surface volume and shape, molecular orbital
      package (MOPAC) and partial charge descriptors and showed a high correlation with
      the inhibitory activity. The descriptors used revealed that a van der Waals (vdW)
      surface with significant polar volume is favourable to the activity. The positive
      effect of the shape descriptors; PM3-LUMO and vsurf_wp7 and the negative effect
      of GCUT_PEOE_2 indicated that the active site may contain some nucleophilic
      positions that could interact with the ligand and the hydrogen acceptor and/or
      donor groups for hydrogen bonding with inhibitors.

PMID- 21171897
TI  - Molecular engineering of a small trypsin inhibitor based on the binding loop of
      horsegram seed Bowman-Birk inhibitor.
AB  - CONTEXT: The Bowman-Birk inhibitors (BBIs) are currently investigated with
      renewed interest due to their therapeutic properties in cancer and other
      inflammatory disease treatment. The molecular mass of the BBI is a limitation, as
      sufficient amounts of the inhibitor do not reach the organs outside the
      gastrointestinal tract when administered orally. METHOD: The anti-tryptic domain
      of HGI-III of horsegram (Dolichos biflorus) was cloned using the vector pET-20b
      (+) and expressed in E. coli BL21 (DE3) pLysS. RESULTS: Kinetic analysis of this
      anti-tryptic peptide (recombinant trypsin inhibitory domain (rTID)) reveals that
      it is a potent inhibitor of trypsin and human tryptase. The K(i) (3.2 +/- 0.17 *
      10(-8) M) establishes a very high affinity to bovine trypsin. rTID inhibited
      human lung tryptase (IC(50) 3.78 +/- 0.23 * 10(-7) M). The rTID is resistant to
      the digestive enzymes found in humans and animals. CONCLUSION: These properties
      propagate further research on the use of rTID as a therapeutic for cancer and
      other related inflammatory diseases.

PMID- 21171898
TI  - Design, synthesis, and preliminary in vitro and in vivo pharmacological
      evaluation of 2-{4-[4-(2,5-disubstituted thiazol-4-yl)phenylethyl]piperazin-1-yl}
      1,8-naphthyridine-3-carbonitriles as atypical antipsychotic agents.
AB  - A series of 2-{4-[4-(2,5-disubstituted thiazolyl)phenylethyl] piperazin-1-yl}-1,8
      naphthyridine-3-carbonitriles were synthesized in an effort to prepare novel
      atypical antipsychotic agents. The compounds were synthesized either by microwave
      irradiation technique or by conventional synthesis and were characterized by
      spectral data (IR, (1)H NMR, and MS) and the purity was ascertained by
      microanalysis. The D(2) and 5-HT(2A) affinity of the synthesized compounds was
      screened in vitro by radioligand displacement assays on membrane homogenates
      isolated from rat striatum and rat cortex, respectively. Furthermore, all the
      synthesized compounds were screened for their in vivo pharmacological activity in
      Swiss albino mice. The D(2) antagonism studies were performed using climbing
      mouse assay model and 5-HT(2A) antagonism studies were performed using quipazine
      induced head twitches in mice. It was observed that none of the new chemical
      entities exhibited catalepsy and 10f is the most active among the synthesized
      compounds with 5-HT(2A)/D(2) ratio of 1.1286 although the standard drug
      risperidone exhibited 5-HT(2A)/D(2) ratio of 1.0989.

PMID- 21171899
TI  - Novel oxazine skeletons as potential antiplasmodial active ingredients:
      Synthesis, in vitro and in vivo biology of some oxazine entities produced via
      cyclization of novel chalcone intermediates.
AB  - A novel series of 6-(2-chloroquinolin-3-yl)-4-substituted-phenyl-6H-1,3-oxazin-2
      amines were synthesized and evaluated for in vitro antimalarial efficacy against
      chloroquine sensitive (MRC-02) as well as chloroquine resistant (RKL9) strains of
      Plasmodium falciparum. The activity tested was at nanomolar concentration. beta
      Hematin formation inhibition activity (BHIA(50)) of oxazines were determined and
      correlated with antimalarial activity. A reasonably good correlation (r = 0.49
      and 0.51, respectively) was observed between antimalarial activity (IC(50)) and
      BHIA(50). This suggests that antimalarial mode of action of these compounds seems
      to be similar to that of chloroquine and involves the inhibition of hemozoin
      formation. Some of the compounds were showing better antimalarial activity than
      chloroquine against resistant strain of P. falciparum and were also found to be
      active in the in vivo experiment.

PMID- 21171900
TI  - Looking through a distorted mirror: toward a psychodynamic understanding of
      descriptive psychopathology of depression.
AB  - Psychodynamic psychiatrists and psychotherapists commonly believe that a shared
      reliance on the descriptive psychopathology of depression could allow a greater
      integration of dynamic treatments with other treatment models. However, the
      assumption that a descriptive approach can offer clinicians a theory independent
      language is epistemologically untenable.

PMID- 21171901
TI  - Commentary on "Looking through a distorted mirror: toward a psychodynamic
      understanding of descriptive psychopathology of depression" by Paolo Azzone.

PMID- 21171902
TI  - Suicide fantasy as a life-sustaining recourse.
AB  - The suicide literature tends to lump all suicidal ideation together, thereby
      implying that it is all functionally equivalent. However obvious the claim that
      suicidal ideation is usually a prelude to suicidal action, some suicidal
      daydreaming tends to inhibit suicidal action. How are we to distinguish between
      those daydreams that augur an impending attempt from those that help patients
      calm down?

PMID- 21171903
TI  - The rise and fall of the autochthonous self: from Italian Renaissance art and
      Shakespeare to Heidegger, Lacan, and intersubjectivism.
AB  - This article addresses the unresolved question of the existence of a private core
      autochthonous self, as it has been described by Winnicott, Modell, and others.
      The postmodern version of the self has eliminated this concept entirely,
      relegating the self to a changing and unstable display, or regarding it as
      totally chaotic, or even an illusion. The question is raised whether by returning
      to the origins of this notion of a private self and then tracing its apparent
      dissolution it might be possible to discover some evidence that it still exists.
      The methodology used is that of obtaining knowledge directly through the arts and
      the claim is made that because empirical science has clamored to be the only
      source of knowledge, we have lost what could be obtained by direct intuitive
      seeing and experiencing the works of creative geniuses. To explore the rise of
      the autochthonous self this article provides an examination of the shift from
      Gothic art to Italian Renaissance art, a time which engendered the origin of
      "man" with his or her elusive private individual self that then became expressed
      in changing works of art. As this spread north, Shakespeare appeared and
      similarly invented and illustrated in his characters the private individual self,
      a concept not appreciated or recognized before the renaissance. But as science
      arose and Western civilization began to decline, a corresponding disillusionment
      with "man" took place. The self began to be viewed as solely a social
      construction with no core except perhaps a genetic endowment. This was
      accompanied by a reduction in the concept of the human as a valuable and precious
      living being and was replaced by regarding the human as an object of control and
      exploitation. After the Second World War a movement in contemporary United States
      psychoanalysis gradually replaced the ideas of Freud and his emphasis on the "I"
      in the psychoanalytic process, with forms of relational therapy, assuming that
      the self was ab initio intersubjectively formed and could be altered
      fundamentally by focus on intersubjective processes. The author contends that
      this attitude makes it less likely for the psychoanalyst to focus on the
      regressive transferences from which derivatives of the private self arise and to
      grasp the phenomenological whole of the patient.

PMID- 21171904
TI  - Psychodynamic aspects of psychopharmacology.
AB  - This paper presents a framework for understanding the psychodynamic issues
      pertaining to psychopharmacology. It examines the treatment situation from three
      perspectives: the self-in-relation-to-others, the patient-prescriber
      relationship, and cultural attitudes. It discusses psychodynamic factors involved
      in clinical improvement and deterioration. The relevance of these issues is
      discussed and contrasted with the biomedical model of mental illness. It
      concludes by advocating the mindfulness of psychodynamic factors and the
      maintenance of dialectics in clinical practice.

PMID- 21171905
TI  - Do psychotherapists speak to psychopharmacologists? A survey of practicing
      clinicians.
AB  - While more Americans are taking psychotropic medication than ever before,
      psychiatrists are providing less psychotherapy, leading to the prevalence of
      "split-treatment" whereby two professionals provide care. Communication between
      clinicians treating the same patient has traditionally been an accepted principle
      of optimal care, however there has been no published data documenting whether or
      not private practice therapists actually do communicate with the psychiatrists
      who prescribe for their patients. A pilot study was conducted in which a nine
      item anonymous survey was distributed to non-medical psychotherapists in
      Manhattan. Information was gathered about professional degree and discipline,
      duration and size of practice, and frequency of communication with professionals
      who prescribe for their patients. Fifty-three psychotherapists averaging over 21
      years in practice returned completed surveys. Respondents reported on 1,197
      psychotherapy patients, with 434 (36%) concurrently taking medication. No
      communication had taken place between psychotherapist and psychopharmacologist on
      behalf of 22% of the psychotherapy patients taking medication. Only 7 of the 53
      respondents reported having quarterly communication with the prescribing
      physician for all split-care patients. Despite methodological limitations, study
      findings document that communication between professionals is not taking place on
      behalf of many patients in split-treatment. These findings raise questions about
      the quality and safety of treatment delivered in this fashion, about the need for
      guidelines for the conduct of split treatment, and perhaps about the
      traditionally assumed need for communication itself.

PMID- 21171906
TI  - Reflections: can the analyst share a traumatizing experience with a traumatized
      patient?
AB  - This is a personal account of a dreadful event in the analyst's life that was
      similar to a patient's trauma. It is a reflection on how the analyst dealt with
      her own trauma, the patient's trauma, and the transference and
      countertransference dynamics. Included is a description of the analyst's inner
      struggles with self-disclosure, continuance of her professional work, and the
      need for persistent self-scrutiny. The meaning of objects in people's life,
      particularly the concept of home, will be addressed.

PMID- 21171907
TI  - Aspects of psychodynamic neuropsychiatry I: episodic memory, transference, and
      the oddball paradigm.
AB  - Psychotherapy has, since the time of Freud, focused on the unconscious and
      dynamically repressed memory. This article explores a therapy where the focus is
      on what is known, on episodic memory. Episodic memory, along with semantic
      memory, is part of the declarative memory system. Episodic memory depends on
      frontal, parietal, as well as temporal lobe function. It is the system related to
      the encoding and recall of context-rich memory. While memory usually decays with
      time, powerfully encoded episodic memory may augment. This article explores the
      hypothesis that such augmentation is the result of conditioning and kindling.
      Augmented memory could lead to a powerful "top-down" focus of attention-such that
      one would perceive only what one had set out to perceive. The "oddball paradigm"
      is suggested as a route out of such a self-perpetuating system. A clinical
      example (a disguised composite of several clinical histories) is used to
      demonstrate how such an intensification of memory and attention came about as a
      result of the transference, and how the "oddball paradigm" was used as a way out
      of what had become a treatment stalemate.

PMID- 21171908
TI  - Brief communication: Self-analysis as an appropriate ending.
AB  - This article is based on Bowlby's attachment theory. Following Bowlby, therapy is
      viewed as a secure base from which to explore. The final achievement of
      independence can be encouraged by self-analysis. A review of the literature on
      self-analysis is focused on Freud, Horney, and Fromm. Self-analysis can be the
      primary aim from the start, or it can be the outcome of a training or a
      therapeutic analysis. An example taken from therapeutic analysis is given. In the
      discussion, the various types of attachment are reviewed. Therapy is viewed as
      leading from insecure to secure attachment, and finally to autonomy.

PMID- 21171912
TI  - Clinical safety and efficacy of everolimus-eluting stents compared to paclitaxel
      eluting stents in patients with coronary artery disease.
AB  - BACKGROUND: the everolimus-eluting stent (EES) is a second-generation drug
      eluting stent (DES) which is designed to provide better stent deliverability,
      deployment, safety, and efficacy. We performed a meta-analysis to evaluate the
      relative safety and efficacy of the EES compared with the paclitaxel-eluting
      stent (PES). METHODS: the published literature was scanned by formal searches of
      electronic databases from January 2001 to August 2010. All randomized trials
      comparing EES versus PES and reporting the clinical outcomes were examined for
      analysis. RESULTS: a total of four randomized trials were included, involving
      6,788 patients. EES were superior to PES with respect to the major adverse
      cardiac events (cardiac death, myocardial infarction (MI), and ischemia-driven
      target lesion revascularization (TLR)) within 1-year follow-up (OR 0.57; P <
      0.001). The 1-year rates of MI, ischemia-driven TLR, and definite or probable
      stent thrombosis (ST) were also lower with EES than with PES (OR 0.57, P < 0.001
      for MI; OR 0.48, P < 0.001 for TLR; OR 0.34, P < 0.001 for ST). There was no
      significant difference between EES and PES with respect to cardiac mortality (OR
      0.93; P = 0.81). CONCLUSION: the EES is superior to the PES in terms of 1-year
      safety and efficacy.

PMID- 21171913
TI  - Innovation versus evidence: to trust direct-to-consumer personal genomic tests?

PMID- 21171914
TI  - Microarray technology displays the complexities of the humoral immune response.

PMID- 21171915
TI  - Molecular diagnostics for monitoring and predicting therapeutic effect in cancer.

PMID- 21171917
TI  - QuantiFERON(r)-CMV assay for the assessment of cytomegalovirus cell-mediated
      immunity.
AB  - Cytomegalovirus (CMV) infection has historically been a major complication among
      immunocompromised patients, such as solid-organ and stem-cell transplant
      recipients and patients with advanced HIV infection. While the introduction of
      antiretroviral therapy has almost eradicated CMV infection in HIV-infected
      patients, CMV disease remains a significant problem in transplant recipients once
      antiviral prophylaxis is discontinued. QuantiFERON((r))-CMV allows the assessment
      of cellular immunity against CMV by detecting the production of IFN-gamma
      following in vitro stimulation with CMV antigens. Preliminary studies have shown
      a correlation between a lack of detectable cell-mediated immunity measured by the
      QuantiFERON-CMV assay and a higher incidence of CMV infection and disease in
      immunocompromised patients. Measurement of cell-mediated immunity against CMV
      appears to be a promising strategy to identify patients at highest risk for the
      development of CMV disease and, therefore, to individualize preventive strategies
      for CMV in transplant recipients.

PMID- 21171918
TI  - New dimensionality reduction methods for the representation of high dimensional
      'omics' data.
AB  - 'Omics' data have increased very rapidly in quantity and resolution, and are
      increasingly recognized as very valuable experimental observations in the
      systematic study of biological phenomena. The increase in availability,
      complexity and nonexpert interest in such data requires the urgent development of
      accurate and efficient dimensionality reduction and visualization techniques. To
      illustrate this need for new approaches we extensively discuss current
      methodology in terms of the limitations encountered. We then illustrate a recent
      example of how combinations of existing techniques can be used to overcome some
      of the present limitations, and discuss possible future directions for research
      in this important field of study.

PMID- 21171919
TI  - Pandemic H1N1 2009 ('swine flu'): diagnostic and other challenges.
AB  - Pandemic H1N1 2009 ('swine flu') virus was 'the virus of the year 2009' because
      it affected the lives of many people in this year. H1N1 was first described in
      California in April 2009 and spread very rapidly all over the globe. The fast
      global penetration of the swine flu caused the WHO in Geneva to call the
      infection with H1N1 a new pandemic with a rapid escalation of the different
      pandemic phases that ended on 11 June 2009, with the declaration of phase 6 (full
      blown pandemic). This had far-reaching consequences for the local health
      authorities in the different affected countries and created awareness in the
      public and fear in the experts and even more so in many lay people. The
      consequences were: setting up reliable diagnostic tests as soon as possible;
      enhanced production, distribution and stock creation of the few drugs that were
      available to treat newly infected persons; and development, production,
      distribution and stock creation of new and appropriate anti-H1N1 swine flu
      vaccines. This all resulted in enormous costs in the local healthcare systems and
      also required smart and diligent logistics, because demand for all this was, in
      most cases, much higher than availability. Fortunately, the pandemic ended quite
      quickly (there was no 'second wave' as had been anticipated by some experts) and
      the death toll was moderate, compared with other influenza pandemic in the past
      and even to the regular annual appearance of the seasonal flu. This favorable
      outcome, however, provoked some harsh criticism that the WHO and healthcare
      systems in general had over-reacted and by doing so, a lot of money was thrown
      out of the window. This article describes the history of the H1N1 pandemic, the
      diagnostic challenges and resolutions, touches on treatment and vaccination very
      briefly and also comments on the criticism and arguments that came up immediately
      at the end and following the termination of the pandemic situation.

PMID- 21171920
TI  - RT-PCR/electrospray ionization mass spectrometry approach in detection and
      characterization of influenza viruses.
AB  - Reverse-transcription PCR (RT-PCR) coupled with electrospray ionization mass
      spectrometry (ESI-MS) is a high-throughput nucleic acid-based technology that
      relies on the accurate measurement of the molecular weight of PCR amplicons that
      can be used to deduce the base counts (number of As, Gs, Cs and Ts) of DNA. These
      amplicons represent highly variable regions with information-rich sequences,
      which are flanked by broad-range primers designed based on highly conserved loci.
      This technology was first introduced in 2005 for microbial identification and
      subtyping, and was later applied to influenza virus detection and identification.
      The influenza RT-PCR/ESI-MS assay allows analysis of approximately 300 samples
      per 24 h, and aids in the characterization of influenza viruses based on their
      'core' gene signatures. Notably, this assay was used to identify one of the first
      cases of the 2009 H1N1 pandemic viruses. One of the main advantages of the RT
      PCR/ESI-MS technology is its universality and adaptability for pathogen
      characterization. Efforts are being made to customize the currently used
      influenza surveillance assay for use in the diagnosis of the H1N1 pandemic virus.
      In this article, we provide a summary of known applications of the RT-PCR/ESI-MS
      assay in the field of influenza.

PMID- 21171921
TI  - Hepatitis C virus RNA assays: current and emerging technologies and their
      clinical applications.
AB  - Molecular diagnostic assays represent a cornerstone in the management of
      hepatitis C virus (HCV) patients. Qualitative and quantitative HCV molecular
      assays are used for the diagnosis of acute and chronic HCV infections, viral
      genotyping, viral-load determination, treatment monitoring and prognosis. Reverse
      transcription PCR, transcription-mediated amplification and branched DNA
      amplification are commonly employed for detection of HCV RNA. Recently, new HCV
      molecular assays that employ nanostructures have emerged and have been proposed
      as suitable for both low- and high-resource settings, without sacrificing
      sensitivity and specificity. This article will present current and future HCV
      molecular diagnostic assays with a focus on their clinical applications.

PMID- 21171922
TI  - Blood-based diagnostics of traumatic brain injuries.
AB  - Traumatic brain injury is a major health and socioeconomic problem that affects
      all societies. However, traditional approaches to the classification of clinical
      severity are the subject of debate and are being supplemented with structural and
      functional neuroimaging, as the need for biomarkers that reflect elements of the
      pathogenetic process is widely recognized. Basic science research and
      developments in the field of proteomics have greatly advanced our knowledge of
      the mechanisms involved in damage and have led to the discovery and rapid
      detection of new biomarkers that were not available previously. However,
      translating this research for patients' benefits remains a challenge. In this
      article, we summarize new developments, current knowledge and controversies,
      focusing on the potential role of these biomarkers as diagnostic, prognostic and
      monitoring tools of brain-injured patients.

PMID- 21171924
TI  - Tumor-associated macrophages in breast cancer as potential biomarkers for new
      treatments and diagnostics.
AB  - While several inflammatory cell types participate in cancer development,
      macrophages specifically play a key role in breast cancer, where they appear to
      be part of the pathogenesis of high-grade tumors. Tumor-associated macrophages
      (TAMs) produce factors that promote angiogenesis, remodel tissue and dampen the
      immune response to tumors. Specific macrophage types contribute to increased
      metastases in animal models, while human studies show an association between TAMs
      and tumors with poor prognostic features. Macrophages display a spectrum of
      phenotypic states, with the tumor microenvironment skewing TAMs towards a
      'nonclassical' activation state, known as the M2, or wound healing/regulatory
      state. These TAMs are found in high-risk breast cancers, making them an important
      therapeutic target to explore. Improved techniques for identifying TAMs should
      translate into clinical applications for prognosis and treatment.

PMID- 21171923
TI  - miRNAs: roles and clinical applications in vascular disease.
AB  - miRNAs are small, endogenously expressed noncoding RNAs that regulate gene
      expression, mainly at the post-transcriptional level, via degradation or
      translational inhibition of their target mRNAs. Functionally, an individual miRNA
      can regulate the expression of multiple target genes. The study of miRNAs is
      rapidly growing and recent studies have revealed a significant role of miRNAs in
      vascular biology and disease. Many miRNAs are highly expressed in the
      vasculature, and their expression is dysregulated in diseased vessels. Several
      miRNAs have been found to be critical modulators of vascular pathologies, such as
      atherosclerosis, lipoprotein metabolism, inflammation, arterial remodeling,
      angiogenesis, smooth muscle cell regeneration, hypertension, apoptosis,
      neointimal hyperplasia and signal transduction pathways. Thus, miRNAs may serve
      as novel biomarkers and/or therapeutic targets for vascular disease. This article
      summarizes the current studies related to the disease correlations and functional
      roles of miRNAs in the vascular system and discusses the potential applications
      of miRNAs in vascular disease.

PMID- 21171925
TI  - Tissular and soluble miRNAs for diagnostic and therapy improvement in digestive
      tract cancers.
AB  - Digestive cancers (e.g., gastric, colorectal, pancreatic or hepatocarcinoma) are
      among the most frequently reported cancers in the world, and are characterized by
      invasivity, metastatic potential and poor outcomes. This group includes some of
      the most critical cancers (among them, are those ranked second to forth in cancer
      related mortality) and, despite all sustained efforts, they maintain a profile of
      low survival rates and lack successful therapies. Discovery of biomarkers that
      improve disease characterization may make optimized or personalized therapy
      possible. Novel biomarkers are expected to provide, hopefully, less-invasive or
      noninvasive diagnostic tools that make possible earlier detection of disease.
      Also, they may provide a more reliable selection instrument in the drug discovery
      process. miRNAs, short noncoding RNAs, have emerged in the last few years as
      significant regulators of cellular activities, controlling protein expression at
      the post-transcriptional level, with a significant implication in pathology in
      general and, of most relevance, in cancers. Deregulation of miRNA expression
      levels and some genetic alterations were demonstrated in various cancers,
      including digestive cancers. Investigations in tissue samples have provided a
      considerable amount of knowledge, identifying altered expressions of miRNAs
      associated with tumorigenesis and tumor progression. Overexpression of some tumor
      inducing or tumor-promoting miRNAs was demonstrated, as well as the
      downregulation of tumor-suppressor miRNAs. Both individual miRNAs, as well as
      sets of multiple miRNAs, were set up as candidate biomarkers for diagnostics or
      monitoring, offering relevant insights into tumorigenic mechanisms. Circulating
      miRNAs were demonstrated as valuable instruments in tumor diagnosis and the
      prognosis of digestive cancers (affecting the esophagus, stomach, intestine,
      colorectum, liver and pancreas), and are being investigated thoroughly in order
      to generate and validate less-invasive diagnostic tools with enhanced
      sensitivity.

PMID- 21171928
TI  - News from the Nordic countries.

PMID- 21171927
TI  - Nimotuzumab for pediatric diffuse intrinsic pontine gliomas.
AB  - INTRODUCTION: Diffuse intrinsic pontine gliomas (DIPG) have a poor prognosis: the
      median survival rate is less than one year. Radiotherapy is the only effective
      treatment affording an overall survival of 6 - 9 months. So far, no improvement
      has been achieved with the addition of single/poly-chemotherapy regimens. An
      urgent need is to advance in this field, from both the biological and the
      clinical points of view. AREAS COVERED: Among the few studies providing
      biological information on DIPG, Gilbertson's group demonstrated a significant
      increase in EGFR expression. The activity of nimotuzumab, a humanized anti-EGFR
      monoclonal antibody, was therefore studied within a Phase II trial in 47
      relapsing pediatric patients with DIPG and high-grade gliomas, showing an
      interesting, persistent response, especially in the first group treated. A
      multicenter exploratory study combining nimotuzumab and radiotherapy showed
      disease control and an overall patient survival similar to previous experiences
      along with an improvement in the quality of patient survival and no severe side
      effects. EXPERT OPINION: We recommend considering this combination in the
      armamentarium against DIPG. It might be improved by adding other target drugs/low
      toxicity chemotherapy regimens with a synergistic effect with the anti-EGFR
      component.

PMID- 21171929
TI  - A hospital-based birth weight analysis using computerized perinatal data base for
      a Chinese population.
AB  - OBJECTIVES: We aimed to construct birth weight-for-gestational age nomograms
      based on a computerized perinatal data base in a hospital-based Chinese
      population. METHODS: Retrospectively collected 28,052 singleton deliveries at
      Women and Children's Medical Center, Guangzhou, China. Standard curves of birth
      weight from 27 to 43 week's gestation were computed. The nomograms included the
      5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles and standard deviations.
      RESULTS: 79.9% pregnant women delivered between 38, 39, and 40 gestational week,
      and the mean birth weights are 3160, 3282, and 3388 g, respectively. Preterm
      birth is 5.7%. In general, male birth weights are greater than females at each
      gestational week. The hospital-based Chinese population birth weight is lower
      than that of North American and Scandinavian population. CONCLUSIONS: A different
      standard birth weight is needed for different population. A hospital-based birth
      weight curve by gestational week is established, which can be a useful tool to
      estimate intrauterine fetal growth to define SGA or LGA fetuses.

PMID- 21171930
TI  - Fetal MBL2 haplotypes combined with viral exposure are associated with adverse
      pregnancy outcomes.
AB  - OBJECTIVE: To investigate the roles of inherited polymorphisms in the MBL2 gene
      and exposure to viral infection in the development of a range of adverse
      pregnancy outcomes, including birthweight  < 10th percentile (small-for
      gestational age, SGA), antepartum hemorrhage (APH), pregnancy-induced
      hypertensive disorders (PIHD), and preterm birth (PTB). METHODS: This was a case
      control study using DNA from newborn screening cards of 717 cases (babies with at
      least one of the adverse pregnancy outcomes listed above) and 609 controls, to
      screen for six polymorphisms within the MBL2 gene. These combine to create
      haplotypes with high (HYPA), intermediate (LYQA, LYPA), low (LXPA), and defective
      (HYPD, LYQC, LYPB) circulating MBL2 levels. RESULTS: Significant associations
      were found between variant MBL2 haplotypes and SGA (LYPA  < 32 weeks OR 5.37, 95%
      CI 1.50-17.27), antepartum hemorrhage (LYPA  < 37 weeks OR 2.29, 95% CI 1.25
      4.18), and PIHD (LYQC < 32 weeks (OR 17.89, 95% CI 2.20-139.57). Evidence of
      exposure to infection increased the effect of these associations, (SGA OR 17.00,
      95% CI 1.03-252.48; APH OR 5.67, 95% CI 1.73-18.84; PIHD OR 23.80, 95% CI 1.08
      1414.76), while no evidence of exposure to infection demonstrated no
      associations. PTB was significantly associated with the defective HYPD haplotype
      with evidence of exposure to infection (OR 6.14, 95% CI 1.21-29.89). CONCLUSIONS:
      This research suggests that the combination of fetal MBL2 haplotypes and exposure
      to in utero viral infection increases the risk of adverse pregnancy outcomes,
      including PTB, antepartum hemorrhage, small-for-gestational age and PIHD.

PMID- 21171931
TI  - Progesterone inhibits growth and induces apoptosis in cancer cells through
      modulation of reactive oxygen species.
AB  - OBJECTIVE: Progesterone (P4) has been implicated as a protective factor for
      ovarian and endometrial cancers, yet little is known about its mechanism of
      action. We have shown apoptosis in ovarian and endometrial cancer cells with high
      doses of P4. Increased generation of reactive oxygen species (ROS) and an altered
      redox status have long been observed in cancer cells. The goal of this study was
      to assess the effect of P4 on cell growth, ROS generation, oxidative stress
      markers, and the expression of antioxidant proteins. METHODS: All experiments
      were performed in vitro using cancer cell lines. Cell proliferation was
      determined using MTS proliferation assay. Production of ROS in cells was measured
      with the ROS indicator dye, aminophenyl fluorescein. Alterations in expression of
      antioxidant and apoptotic proteins were assessed by Western blotting. RESULTS:
      The exposure of ovarian and endometrial cancer cell cultures to various doses of
      P4 caused a dose-dependent decrease in cell viability and the activation of
      caspase-3. Levels of ROS, markers of oxidative stress, and antioxidant proteins
      were elevated in cancer cells compared to normal cells and a marked decrease in
      their expression was seen following P4 treatment. In cancer cells, ROS was
      elevated while p-53 expression was low. P4 exposure of cells resulted in
      increased p-53 and BAX and decreased BCL-2 expression. CONCLUSIONS: The data
      indicates that P4 has antioxidant effects. It alleviates ROS stress and causes
      apoptosis by upregulating proapoptotic (p-53 and BAX) and decreasing
      antiapoptotic (BCL-2) gene expression in cancer cells. These findings could have
      potential therapeutic implications.

PMID- 21171932
TI  - Low-intensity ultrasound increased colony forming unit-fibroblasts of mesenchymal
      stem cells during primary culture.
AB  - Mesenchymal stem cells (MSCs) from bone marrow (BM) are an attractive cell source
      for stem cell-based therapeutic applications, but they exist at low-end ratios,
      which further decreases along with increased donor age. Thus, for clinical
      applications, there is a high demand for large numbers of active MSCs. This study
      investigated if low-intensity ultrasound (LIUS), a special type of mechanical
      stimulation, could increase the yield of MSCs during primary culture from the BM.
      Cultures were treated with LIUS for 10 min/day during the first 6 days after
      initial plating of BM mononuclear cells. After 12 days, the colony-forming unit
      fibroblasts assay was performed, and the colonies were culture-expanded for
      further analyses. The LIUS stimulation showed a significant increase in the
      number of MSCs colonies when compared with that of the control group. The LIUS
      stimulated MSCs showed no difference compared with the untreated control MSCs in
      terms of their proliferation rate, expression of MSCs-enriched surface antigens,
      and multi-lineage differentiation ability. The LIUS stimulation also showed an
      increase in the expression of integrins, fibronectin, and paxillin, and induced
      the formation of focal adhesions in MSCs, all of which involved in the cell
      adhesion process. These results demonstrated that LIUS stimulation could activate
      the cell adhesion process and increase the colony-forming ability of MSCs during
      the early stage of primary culture, without affecting their phenotypes and multi
      potency. The results of this study suggest that LIUS could be a useful tool to
      obtain a large amount of MSCs for various therapeutic applications.

PMID- 21171934
TI  - A perfusion bioreactor for engineering bone constructs: an in vitro and in vivo
      study.
AB  - A perfusion bioreactor, which was designed based on fluidized bed concepts, was
      validated for the culture of bone constructs of clinically relevant size. For
      this study, natural coral has been used as three-dimensional scaffolds. This
      biomaterial is a microporous, biocompatible, osteoconductive, and absorbable
      scaffold. This perfusion bioreactor provided a stable environment in terms of
      osmolarity, pH, and, most importantly, oxidative stress. Bone constructs
      engineered in this system resulted in significantly higher cell proliferation and
      homogenous cell distribution than those cultured under static conditions.
      Particularly relevant to the production of bioengineered bone in a clinical
      setting, custom-made bone constructs (each one with volume up to 30 cm(3)) could
      be produced using a such perfusion bioreactor. Last, but not least, the bone
      constructs of clinically relevant volume thus produced were shown to be
      osteogenic when transplanted subcutaneously in sheep.

PMID- 21171933
TI  - HIV, alcohol dependence, and the criminal justice system: a review and call for
      evidence-based treatment for released prisoners.
AB  - BACKGROUND: People with both HIV and alcohol use disorders (AUDs) are
      disproportionately concentrated within the U.S. criminal justice system;
      approximately one-quarter of all people with HIV cycle through the system each
      year. HIV-infected prisoners with AUDs face many obstacles as they transition
      back to the community. Specifically, although they have impressive HIV treatment
      outcomes during the period of incarceration while they are free from alcohol;
      upon [corrected] release, however, they face inordinate challenges including
      relapse to alcohol use resulting in significant morbidity and mortality.
      OBJECTIVE: To review the existing literature regarding the relationship of HIV
      and treatment for AUDs within the criminal justice system in an effort to
      determine "best practices" that might effectively result in improved treatment of
      HIV and AUDs for released prisoners. METHODS: PubMed, PsychInfo and Medline were
      queried for articles published in English from 1990 to 2009. Selected references
      from primary articles were also examined. RESULTS: Randomized controlled trials
      affirm the role of pharmacotherapy using naltrexone (NTX) as the therapeutic
      option conferring the best treatment outcome for AUDs in community settings.
      Absent from these trials were inclusion of released prisoners or HIV-infected
      individuals. Relapse to alcohol abuse among HIV-infected prisoners is associated
      with reduced retention in care, poor adherence to antiretroviral therapy with
      consequential poor HIV treatment outcomes and higher levels of HIV risk
      behaviors. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Untreated alcohol dependence,
      particularly for released HIV-infected prisoners, has negative consequences both
      for the individual and society and requires a concentrated effort and rethinking
      of our existing approaches for this vulnerable population.

PMID- 21171936
TI  - Herbal treatments for alleviating premenstrual symptoms: a systematic review.
AB  - Premenstrual syndrome (PMS) is a condition of cyclical and recurrent physical and
      psychological discomfort occurring 1 to 2 weeks before menstrual period. More
      severe psychological symptoms have been described for the premenstrual dysphoric
      disorder (PMDD). No single treatment is universally recognised as effective and
      many patients often turn to therapeutic approaches outside of conventional
      medicine. This systematic review is aimed at analysing the effects of herb
      remedies in the above conditions. Systematic literature searches were performed
      in electronic databases, covering the period January 1980 to September 2010.
      Randomised controlled clinical trials (RCTs) were included. Papers quality was
      evaluated with the Jadad' scale. A further evaluation of PMS/PMDD diagnostic
      criteria was also done. Of 102 articles identified, 17 RCTs were eligible and 10
      of them were included. The heterogeneity of population included, study design and
      outcome presentation refrained from a meta-analysis. Vitex agnus castus was the
      more investigated remedy (four trials, about 500 women), and it was reported to
      consistently ameliorate PMS better than placebo. Single trials also support the
      use of either Gingko biloba or Crocus sativus. On the contrary, neither evening
      primrose oil nor St. John's Wort show an effect different than placebo. None of
      the herbs was associated with major health risks, although the reduced number of
      tested patients does not allow definitive conclusions on safety. Some herb
      remedies seem useful for the treatment of PMS. However, more RCTs are required to
      account for the heterogeneity of the syndrome.

PMID- 21171935
TI  - Statins have an early antiplatelet effect in patients with acute myocardial
      infarction.
AB  - Statins confer an antiplatelet effect in hypercholesterolemic subjects and in
      stable coronary artery disease patients. We explored the antiplatelet effects of
      statins in ST-elevation myocardial infarction (STEMI) patients undergoing primary
      angioplasty. Of 120 STEMI patients, 80 (67%) received statins while 40 (33%) did
      not. Ex vivo platelet reactivity was studied on admission and 72 hours later by
      conventional aggregometry and under flow conditions (Impact R). Measures of
      platelet reactivity under flow conditions included aggregate size and surface
      coverage, signifying platelet aggregation and adhesion respectively. The effect
      of statins on platelet function under flow conditions and platelet aggregation
      was studied in?vitro in platelets from 10 STEMI patients. Platelets from each
      patient were incubated in?vitro with lovastatin or PBS as a control. The effect
      of lovastatin in the presence of a nitric oxide synthase inhibitor (L-NMMA) was
      also studied. Patients treated with statins were compared with those who did not
      have significantly lower ADP-induced platelet aggregation on the 4th day (56 +/-
      18% vs. 64 +/- 17%, p=0.02). Platelet deposition under flow conditions as
      measured by surface coverage was reduced from admission to 72 hours later among
      statin-treated patients (19 +/- 28% reduction, p<0.01), but was unchanged in non
      treated patients (for comparison p<0.01). The extent of platelet inhibition was
      unrelated to patient characteristics, including lipid profile and type of statin
      administered (lipophylic vs. hydrophilic). In the in vitro study platelet
      incubation with statin compared with PBS resulted in a lower aggregate-size (29
      +/- 9 MUm(2) vs. 39 +/- 15 MUm(2), p<0.01), and lower surface coverage (8.5 +/-
      4% vs. 12 +/- 4%, p<0.01). The effect of the statin on both parameters was
      significantly blunted by L-NMMA. Incubation with statin also resulted in a
      reduction in collagen-induced platelet aggregation (31 +/- 20% vs. 54 +/- 25%,
      p<0.01). We concluded that in acute myocardial infarction patients, statins have
      an early antiplatelet effect, in addition to that afforded by standard
      antiplatelet therapy.

PMID- 21171938
TI  - Amylase and lipase detection in hemorrhaged animals treated with HBOC-201.
AB  - HBOC-201 may alter lipase and amylase detection on chemistry analyzers using
      optical methods and affect pancreatic function after trauma. Amylase and lipase
      measurements were correlated against HBOC-201 to evaluate interference on samples
      spiked with 0-6g/dL HBOC-201. The detection threshold was 2.5g/dL or none when
      measured, respectively, on Vitros 250 or Advia 1650 instruments. Amylase and
      lipase from blood samples collected from 55% EBV hemorrhaged Yucatan min-pigs
      showed peaks around 24-48 hours. Amylase increase was not significant between
      treatments but lipase was higher in HBOC-201-treated animals. Animals
      particularly affected by the injury had elevated enzymes after hemorrhagic shock,
      without significant clinical consequences.

PMID- 21171937
TI  - Androgen replacement therapy contributes to improving lower urinary tract
      symptoms in patients with hypogonadism and benign prostate hypertrophy: a
      randomised controlled study.
AB  - PURPOSE: We performed a randomised controlled study regarding the effects of
      androgen replacement therapy (ART) on lower urinary tract symptoms (LUTS) in
      hypogonadal men with benign prostate hypertrophy (BPH). METHODS: Fifty-two
      patients with hypogonadism and BPH were randomly assigned to receive testosterone
      (ART group) as 250 mg of testosterone enanthate every 4 weeks or to the untreated
      control group. We compared International Prostate Symptom Score (IPSS),
      uroflowmetry data, post-voiding residual volume (PVR) and systemic muscle volume
      at baseline and 12 months after treatment. RESULTS: Forty-six patients (ART
      group, n=23; control, n=23) were included in the analysis. At the 12-month visit,
      IPSS showed a significant decrease compared with baseline in the ART group (15.7
      +/- 8.7 vs. 12.5 +/- 9.5; p<0.05). No significant changes were observed in the
      control group. The ART group also showed improvement in maximum flow rate and
      voided volume (p<0.05), whereas no significant improvements were observed in the
      controls. PVR showed no significant changes in either group. In addition, the ART
      group showed significant enhancement of mean muscle volume (p<0.05), whereas no
      significant changes were seen in the controls. CONCLUSION: ART improved LUTS in
      hypogonadal men with mild BPH.

PMID- 21171939
TI  - One-year, simultaneous combined exposure of CDMA and WCDMA radiofrequency
      electromagnetic fields to rats.
AB  - PURPOSE: We investigated whether one-year, long-term, simultaneous exposure to
      code division multiple access (CDMA; 849 MHz) and wideband code division multiple
      access (WCDMA; 1.95 GHz) radiofrequencies (RF) would induce chronic illness in
      Sprague-Dawley (SD) rats. MATERIALS AND METHODS: Two groups of 40 SD rats (50%
      males and females in sham and exposed groups) were exposed to CDMA and WCDMA RF
      simultaneously at 2.0 W/kg for 45 min/day (total 4.0 W/kg), 5 days per week for a
      total of one year. Body and organ weight measurements, urinalysis, haematological
      and blood biochemical analysis, and histopathological evaluations were performed.
      RESULTS: The mortality patterns in male and female rats exposed to RF were
      compared with those found in gender-matched sham control animals. No significant
      alteration in body weight was observed with the simultaneous combined RF
      exposure. Most RF-exposed rats showed no significant alteration, based on
      urinalysis, haematology, blood biochemistry, or histopathology. However, some
      altered parameters of the complete blood count and serum chemistry were seen in
      RF-exposed rats. The total tumour incidence was not different between sham
      exposed and RF-exposed animals. CONCLUSIONS: Our results suggest that one-year
      chronic exposure to CDMA (849 MHz) and WCDMA (1.95 GHz) RF simultaneously at 2.0
      W/kg for 45-min RF exposure periods (total, 4 W/kg) did not increase chronic
      illness in rats, although there were some altered parameters in the complete
      blood count and serum chemistry.

PMID- 21171941
TI  - Human sex ratio at birth and related factors.

PMID- 21171940
TI  - RBE of alpha-particles from (211)At for complex DNA damage and cell survival in
      relation to cell cycle position.
AB  - PURPOSE: To investigate cell cycle effects and relative biological effectiveness
      (RBE) of alpha-particles from the clinically relevant radionuclide Astatine-211
      ((211)At), using X-rays as reference radiation. Double-strand breaks (DSB), non
      DSB clusters containing oxidised purines and clonogenic survival were
      investigated. MATERIALS AND METHODS: Asynchronous V79-379A fibroblasts or cells
      synchronised with mimosine in G1, early, mid and late S phase or in mitosis were
      irradiated with X-rays (100 kV(p)) or (211)At (mean linear energy transfer (LET)
      110 keV/MUm). Induction of DSB and clusters was determined using pulsed-field gel
      electrophoresis with fragment analysis. Cell survival was obtained with the
      clonogenic assay. RESULTS: In asynchronous cells RBE for DSB- and cluster
      induction was 3.5 and 0.59, respectively. RBE for 37% cell survival was 8.6. In
      different cell cycle phases RBE varied from 1.8-3.9 for DSB and 3.1-7.9 for 37%
      survival (survival at 2 Gy was 6.9-38 times lower after alpha-irradiation).
      (211)At induced 6 times more DSB and X-rays induced 11 times more DSB in mitotic
      cells with highly compacted chromatin relative G1. CONCLUSIONS: The radio
      response is cell cycle dependent and differs between proliferating and non
      cycling cells for both low- and high-LET radiation, resulting in a variation in
      RBE of alpha-particles between 1.8 and 8.6.

PMID- 21171942
TI  - Quantitative ultramicrotest for newborn screening of galactosemia in Cuba.
AB  - BACKGROUND: To describe a simple, rapid, quantitative ultramicrotest (UMTEST)
      based on the fluorometric method introduced by Fujimura et al. adapted to an
      Ultra Micro Analytic System (SUMA) for the detection of total galactose (GAL) in
      dried blood specimens. METHODS: The assay uses 3 mm discs of dried blood on
      Whatman 903 filter paper and small volumes of each reagent. A
      methanol/acetone/water solution is used for deproteination, and a specially
      designed 96-well polystyrene opaque ultramicroplates, with a maximum capacity of
      30 MUL per well, are used for the reading. RESULTS: The UMTEST GAL is completed
      in 2 h, with measuring range of 0.28-3.92 mmol/L. The intra- and inter-assay
      coefficients of variation were 2.3%-8.9% and 6.8%-11.1%, respectively, depending
      on the total GAL concentrations. Percentage recovery ranged from 97.7% to 103%.
      Limit of detection and limit of quantitation were 0.06 and 0.16 mmol/L,
      respectively. The mean GAL concentration, in 2510 dried blood samples from the
      National Neonatal Screening Program was 0.23 mmol/L. Our assay showed high
      concordance correlations with the commercially available ICN Immuno-ChemTM GAL-MW
      EA kit. CONCLUSIONS: The analytical performance characteristics of this assay is
      suitable for mass newborn screening of galactosemia in Cuba.

PMID- 21171943
TI  - Metal induced conformational changes in human insulin: crystal structures of
      Sr2+, Ni2+ and Cu2+ complexes of human insulin.
AB  - Crystal structures of Sr(2+), Ni(2+) and Cu(2+) of human insulin complexes have
      been determined. The structures of Sr(2+) and Ni(2+) complexes are similar to
      Zn(2+) insulin and are in T6 conformation. (All the six monomers in the insulin
      hexamer are in Tensed conformation (T), which means the first eight residues of B
      chain are in an extended conformation). Cu(2+) complex, though it assumes T6
      conformation, has more structural differences due to lowering of crystal symmetry
      and space group shift from H3 (Hexagonal crystal system) to P3 (Trigonal crystal
      system) and a doubling of the c axis. 2Ni(2+) human insulin when compared to
      4Ni(2+) Arg insulin suggests that terminal modifications may be responsible for
      additional metal binding. All the three metals have been shown to have a role in
      diabetes and hence may be therapeutically useful.

PMID- 21171944
TI  - 3D-QSAR study on a series of Bcl-2 protein inhibitors using comparative molecular
      field analysis.
AB  - In this manuscript, three-dimensional quantitative structure-activity
      relationship (3D-QSAR) studies using comparative molecule field analysis (CoMFA)
      techniques were applied to provide the structural information of Bcl-2
      inhibitors. The CoMFA model obtained from the training set were all statistically
      significant with the cross-validated coefficients (q(2)) of 0.568 and
      conventional coefficients (r(2)) of 0.991. The contribution of steric field and
      the electrostatic field is 0.635 and 0.365, respectively. The 3D-QSAR model was
      furthermore validated by a test set of 6 molecules. The predicted correlation
      coefficient (r(2)(pred)) on the test set is 0.582. Therefore, the 3D-QSAR models
      built may be used to exhibit the necessary ligand-based structural environment as
      well as to design novel Bcl-2 inhibitors with increasing activities.

PMID- 21171945
TI  - On the relation between residue flexibility and residue interactions in proteins.
AB  - B-factor from X-ray crystal structure can well measure protein structural
      flexibility, which plays an important role in different biological processes,
      such as catalysis, binding and molecular recognition. Understanding the essence
      of flexibility can be helpful for the further study of the protein function. In
      this study, we attempted to correlate the flexibility of a residue to its
      interactions with other residues by representing the protein structure as a
      residue contact network. Here, several well established network topological
      parameters were employed to feature such interactions. A prediction model was
      constructed for B-factor of a residue by using support vector regression (SVR).
      Pearson correlation coefficient (CC) was used as the performance measure. CC
      values were 0.63 and 0.62 for single amino acid and for the whole sequence,
      respectively. Our results revealed well correlations between B-factors and
      network topological parameters. This suggests that the protein structural
      flexibility could be well characterized by the inter-amino acid interactions in a
      protein.

PMID- 21171946
TI  - HRV signaling in airway epithelial cells is regulated by ITAM-mediated
      recruitment and activation of Syk.
AB  - Human rhinovirus (HRV), cause of the common cold, is a leading cause of
      exacerbations of asthma and chronic obstruction pulmonary disease (COPD). Binding
      of HRV to ICAM (intercellular adhesion molecule)-1, its major receptor, induces a
      profound inflammatory response from airway epithelial cells. My laboratory has
      identified Syk tyrosine kinase to be an early regulator of HRV-ICAM-1 signalling:
      Syk mediates replication-independent p38 mitogen-activated protein (MAP) kinase
      and phosphatidyl-inositol 3 (PI3)-kinase activation, interleukin (IL)-8
      expression, as well as HRV internalization via clathrin-mediated endocytosis. Syk
      activation is accompanied by formation of a protein complex consisting of ICAM-1,
      ezrin and Syk at the plasma membrane. However, the molecular mechanisms that
      regulate this process are not understood. In this report, we investigated the
      role of the Syk-SH2 domains and the ezrin ITAM (immuno-tyrosine activation motif)
      like motif in HRV-induced cell activation using the human BEAS-2B airway
      epithelial cells. Our observations suggest that the ezrin-ITAM plays a role in
      Syk recruitment and activation by binding to the Syk tandem SH2 domains, as
      originally described in the canonical ITAM-mediating signal transduction pathway
      in hematopoietic cells. This report is the first to demonstrate ITAM-mediated
      signaling in non-hematopoietic cells, suggesting that this signaling paradigm may
      be more ubiquitous than previously recognized.

PMID- 21171947
TI  - Possible reason for cross-species and cross-subtype reassortment in polymerase
      basic protein 2 from influenza A virus.
AB  - The reassortment in proteins from influenza A viruses among human, swine, and
      Eurasian avian strains formed a new influenza A virus leading to the first
      pandemic in this century, which suggests that the barrier between species and
      between subtypes would not be strong enough to prevent the cross-species
      infection and cross-subtype reassortment from occurring. In this study, we
      intensively used the ANOVA including its model I and model II to analyze 2430
      polymerase basic proteins 2 (PB2) of influenza A viruses in order to determine
      whether there is a barrier between species and between subtypes. The results show
      that (i) there is a barrier between HA subtypes, between NA subtypes and between
      hosting species in some cases, however, there is no barrier in most cases, which
      can lead to cross-species infection and cross-subtype reassortment, and (ii) the
      intra-subtype/species variation is larger than the inter-subtype/species
      variation in most cases, which can lead mutations/reassortments in PB2 to easily
      jump from species to species or from subtype to subtype. These results are in
      agreement with our previous studies along this research line in the
      hemagglutinin, neuraminidase, matrix protein 1 and 2 from influenza A virus, and
      provide further explanations for the possible reason for cross-subtype
      reassortment and cross-species infection.

PMID- 21171948
TI  - Evaluation of different glycoforms of honeybee venom major allergen phospholipase
      A2 (Api m 1) produced in insect cells.
AB  - Allergic reactions to hymenoptera stings are one of the major reasons for IgE
      mediated anaphylaxis. However, proper diagnosis using venom extracts is severely
      affected by molecular cross-reactivity. In this study recombinant honeybee venom
      major allergen phospholipase A2 (Api m 1) was produced for the first time in
      insect cells. Using baculovirus infection of different insect cell lines allergen
      versions providing a varying degree of cross-reactive carbohydrate determinants
      as well as a non glycosylated variant could be obtained as secreted soluble
      proteins in high yields. The resulting molecules were analyzed for their
      glycosylation and proved to show advantageous properties regarding cross
      reactivity in sIgE-based assays. Additionally, in contrast to the enzymatically
      active native protein the inactivated allergen did not induce IgE-independent
      effector cell activation. Thus, insect cell-derived recombinant Api m 1 with
      defined CCD phenotypes might provide further insights into hymenoptera venom IgE
      reactivities and contribute to an improved diagnosis of hymenoptera venom
      allergy.

PMID- 21171949
TI  - Isolation and detection of protein with nano-particles and microchips for
      analyzing proteomes on a large scale basis.
AB  - The advent of sugar-immobilized gold nano-particles (SGNPs), lipid-based
      nanoparticles, nano-chromatography and nano-electrophoresis has revolutionized
      the methodology for protein purification and proteomic research. This review
      provides an overview on the effective method developed for fast purification of
      protein from extracts using SGNPs. In addition, the current application of
      microfluidic systems for analytical purposes in biochemistry will also be
      explored that include the micro total analysis systems (u-TAS) and lab-on-a-chip
      (LOC) analyses which are capable of isolation and detection of protein at the
      nanogram level. Finally, we describe why the lipid-based nano-particles (LBNPs)
      can enable the analysis in microchip electroseparation and how anionic and
      cationic LBNPs can be used for protein separation.

PMID- 21171950
TI  - Antiangiogenic agents.

PMID- 21171951
TI  - Recent patents on topical application of honey in wound and burn management.
AB  - Topical application of honey to burn and wounds has been found to be effective in
      controlling infection and producing a clean granulating bed. It is suggested that
      the wound healing effect of honey may in part be related to the release of
      inflammatory cytokines from surrounding tissue cells, mainly monocytes and
      macrophages. It has been reported that honey hastens wound healing by
      accelerating wound contractions. Microscopic evaluation demonstrated that there
      was a significant acceleration of dermal repair in wound treated with honey.
      Macroscopic and microscopic observations under in vivo assessment suggested that
      the topical application of honey might have favourable influences on the various
      phases of burn and wound healing hence accelerating the healing process. The
      regulatory effects of honey are related to components other than the sugars.
      However, the mechanisms by which honey affects the release of anti inflammatory
      agents and growth factors from monocytic cells are as yet unclear. Whether honey
      affects other cell types, particularly endothelial cells and fibroblasts,
      involved in wound healing also needs to be clarified. The present article is a
      short review of recent patents on the healing effect of honey in wound and burn
      management.

PMID- 21171953
TI  - Molecular display technologies--development and improvement of powerful solutions
      in medical, pharmaceutical, and sustainable biotechnology.

PMID- 21171952
TI  - Recent patents and emerging therapeutics in the treatment of allergic
      conjunctivitis.
AB  - Ocular allergy is an inflammatory response of the conjunctival mucosa that also
      affects the cornea and eyelids. Allergic conjunctivitis includes seasonal
      allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), vernal
      keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC) and giant papillary
      conjunctivitis (GPC). In general, allergic conditions involve mast cell
      degranulation that leads to release of inflammatory mediators and activation of
      enzymatic cascades generating pro-inflammatory mediators. In chronic ocular
      inflammatory disorders associated with mast cell activation such as VKC and AKC
      constant inflammatory response is observed due to predominance of inflammatory
      mediators such as eosinophils and Th2-generated cytokines. Antihistamines, mast
      cell stabilizers, nonsteroidal anti-inflammatory agents, corticosteroids and
      immunomodulatory agents are commonly indicated for the treatment of acute and
      chronic allergic conjunctivitis. In recent years newer drug molecules have been
      introduced in the treatment of allergic conjunctivitis. This article reviews
      recent patents and emerging therapeutics in the treatment of allergic
      conjunctivitis.

PMID- 21171954
TI  - Staphylococcal surface display in combinatorial protein engineering and epitope
      mapping of antibodies.
AB  - The field of combinatorial protein engineering for generation of new affinity
      proteins started in the mid 80s by the development of phage display. Although
      phage display is a prime example of a simple yet highly efficient method,
      manifested by still being the standard technique 25 years later, new alternative
      technologies are available today. One of the more successful new display
      technologies is cell display. Here we review the field of cell display for
      directed evolution purposes, with focus on a recently developed method employing
      Gram-positive staphylococci as display host. Patents on the most commonly used
      cell display systems and on different modifications as well as specific
      applications of these systems are also included. General strategies for selection
      of new affinity proteins from cell-displayed libraries are discussed, with
      detailed examples mainly from studies on the staphylococcal display system. In
      addition, strategies for characterization of recombinant proteins on the
      staphylococcal cell surface, with an emphasis on an approach for epitope mapping
      of antibodies, are included.

PMID- 21171955
TI  - An approach to rational ligand-design based on a thermodynamic analysis.
AB  - Thermodynamic analysis is an effective tool in screening of lead-compounds for
      development of potential drug candidates. In most cases, a ligand achieve high
      affinity and specificity to a target protein by means of both favorable enthalpy
      and entropy terms, which can be reflected in binding profiles of Isothermal
      Titration Calorimetry (ITC). A favorable enthalpy change suggests the
      contribution of noncovalent contacts such as hydrogen bonding and van der Waals
      interaction between a ligand and its target protein. In general, optimization of
      binding enthalpy is more difficult than that of entropies in ligand-design;
      therefore, it is desirable to choose firstly a lead-compound based on its binding
      enthalpic gain. In this paper, we demonstrate the utility of thermodynamic
      approach to ligand screening using anti-ciguatoxin antibody 10C9 as a model of a
      target protein which possesses a large hydrophobic pocket. As a result of this
      screening, we have identified three compounds that could bind to the antigen
      binding pocket of 10C9 with a few kcal/mol of favorable binding enthalpy.
      Comparison of their structure with the proper antigen ciguatoxin CTX3C revealed
      that 10C9 rigorously identifies their cyclic structure and a characteristic
      hydroxyl group. ITC measurement might be useful and powerful for a rational
      ligand screening and the optimization of the ligand; the enthalpic gain is an
      effective index for ligand-design studies.

PMID- 21171956
TI  - Developments in high-yield system expressed vaccines and immunotherapy.
AB  - Conventional vaccine production techniques are outdated, leaving the world
      defenseless to viruses and pathogens. Successful protection necessitates the
      innovation of strategies that can generate an induced defensive humoral and
      cellular response with: ease of mass production, nominal side-effects, and
      controlled design specificity, all while being cost effective. Fortunately,
      technology exists to facilitate such advances in this billion dollar industry and
      this review is focused on recent publications and patents which hold promise to
      revolutionize the fight against pathogenic illnesses.

PMID- 21171957
TI  - Development of yeast molecular display systems focused on therapeutic proteins,
      enzymes, and foods: functional analysis of proteins and its application to
      bioconversion.
AB  - Molecular display systems using yeast have been developed for industrial,
      medical, pharmaceutical, and biological studies. Although several host cells are
      available to construct a molecular display system, the yeast Saccharomyces
      cerevisiae is a well-established and convenient organism in eukaryotes. A wide
      variety of prokaryotic and eukaryotic proteins have been displayed on yeast cell
      surfaces. In addition, functional analyses and applications to bioconversion have
      been performed on the cell surface, and cells are conveniently engineered by
      molecular display systems. In this review, we focus on the yeast molecular
      display system with regard to therapeutic proteins, several enzymes, and food
      ingredients. In addition, recent patents on molecular display using yeast cell
      for production of those compounds, screening technology and related techniques
      are introduced. Development of devices for functional analysis of created and
      modified proteins in the yeast display system is also described.

PMID- 21171958
TI  - Bioengineering of bacterial magnetic particles and their applications in
      biotechnology.
AB  - Magnetic particles have attracted much attention for their versatile uses in
      biotechnology, especially in medical applications. The major advantage of
      magnetic particles is that they can be easily manipulated by magnetic forces.
      Magnetotactic bacteria synthesize nano-sized biomagnetites, otherwise known as
      bacterial magnetic particles (BacMPs) that are individually enveloped by a lipid
      bilayer membrane. The mechanisms of BacMP synthesis have been analyzed by
      genomic, proteomic, and bioinformatic approaches. Based on those studies in
      Magnetospirillum magneticum AMB-1, functional nanomaterials have been designed
      and produced. Through genetic engineering, functional proteins such as enzymes,
      antibodies, and receptors have been successfully displayed on BacMPs. These
      functional BacMPs have been utilized in various biosensors and bio-separation
      processes. Here, recent papers and patents for bioengineering of BacMPs and their
      applications in biotechnology are reviewed. The elucidation of the mechanism of
      magnetic particle synthesis has provided a roadmap for the design of novel
      biomaterials that can play useful roles in multiple disciplinary fields.

PMID- 21171959
TI  - Applications of yeast cell-surface display in bio-refinery.
AB  - The dependency on depleting natural resources is a challenge for energy security
      that can be potentially answered by bioenergy. Bioenergy is derived from starchy
      and lignocellulosic biomass in the form of bioethanol or from vegetable oils in
      the form of biodiesel fuel. The acid and enzymatic methods have been developed
      for the hydrolysis of biomass and for transesterifiaction of plant oils. However,
      acid hydrolysis results in the production of unnatural compounds which has
      adverse effects on yeast fermentation. Recent advancements in the yeast cell
      surface engineering developed strategies to genetically immobilize amylolytic,
      cellulolytic and xylanolytic enzymes on yeast cell surface for the production of
      fuel ethanol from biomass. This review gives an insight in to the recent
      technological developments in the production of bioenergy, i.e, bioethanol using
      surface engineered yeast.

PMID- 21171960
TI  - Role of immunostimulatory molecules in poultry vaccines.
AB  - Immunization by vaccination is the most suitable and safest method for preventing
      infectious diseases in the poultry worldwide. Vaccines alone cannot effectively
      protect birds from variety of pathogens under field conditions. The combined use
      of potent immunostimulants in vaccines is an alternative to increase the efficacy
      of vaccines that can be achieved by the development of better adjuvant. One such
      adjuvant is cytokine; cytokines have been used extensively as adjuvant in
      vaccines and are responsible for the type and extent of an immune response
      following vaccination. Although the innate immune system in birds is not fully
      characterized but their immune system is very much similar to that of mammals,
      and moreover with the recent discovery of a number of avian cytokine genes it is
      now possible to study their effectiveness in enhancing the immune response during
      vaccination. This review focuses on the recent studies and developments involving
      the role of immunomodulating agents especially cytokines of avian origin in
      poultry vaccines.

PMID- 21171961
TI  - Green biofactories: recombinant protein production in plants.
AB  - Until recently, low accumulation levels have been the major bottleneck for plant
      made recombinant protein production. However, several breakthroughs have been
      described in the past few years allowing for very high accumulation levels,
      mainly through chloroplast transformation and transient expression, coupled with
      subcellular targeting and protein fusions. Another important factor influencing
      our ability to use plants for the production of recombinant proteins is the
      availability of quick and simple purification strategies. Recent developments
      using oleosin, zein, ELP and hydrophobin fusion tags have shown promise as
      efficient and cost-effective methods for non-chromatographic separation.
      Furthermore, plant glycosylation is a major barrier to the parenteral
      administration of plant-made biopharmaceuticals because of potential
      immunogenicity concerns. A major effort has been invested in humanizing plant
      glycosylation, and several groups have been able to reduce or eliminate
      immunogenic glycans while introducing mammalian-specific glycans. Finally,
      biosafety issues and public perception are essential for the acceptance of plants
      as bioreactors for the production of proteins. Over recent years, it has become
      clear that food and feed plants carry an inherent risk of contaminating our food
      supply, and thus much effort has focused on the use of non-food plants.
      Presently, Nicotiana benthamiana has emerged as the preferred host for transient
      expression, while tobacco is most frequently used for chloroplast transformation.
      In this review, we focus on the main issues hindering the economical production
      of recombinant proteins in plants, describing the current efforts for addressing
      these limitations, and we include an extensive list of recent patents generated
      with the intention of solving these limitations.

PMID- 21171962
TI  - Chemical agents positively and negatively affecting the central nervous system.

PMID- 21171963
TI  - Functional analysis of RhoGDI inhibitory activity on vacuole membrane fusion.
AB  - RhoGDIs (Rho GDP-dissociation inhibitors) are the natural inhibitors of Rho
      GTPases. They interfere with Rho protein function by either blocking upstream
      activation or association with downstream signalling molecules. RhoGDIs can also
      extract membrane-bound Rho GTPases to form soluble cytosolic complexes. We have
      shown previously that purified yeast RhoGDI Rdi1p, can inhibit vacuole membrane
      fusion in vitro. In the present paper we functionally dissect Rdi1p to discover
      its mode of regulating membrane fusion. Overexpression of Rdi1p in vivo
      profoundly affected cell morphology including increased actin patches in mother
      cells indicative of polarity defects, delayed ALP (alkaline phosphatase) sorting
      and the presence of highly fragmented vacuoles indicative of membrane fusion
      defects. These defects were not caused by the loss of typical transport and
      fusion proteins, but rather were linked to the reduction of membrane localization
      and activation of Cdc42p and Rho1p. Subcellular fractionation showed that Rdi1p
      is predominantly a cytosolic monomer, free of bound Rho GTPases. Overexpression
      of endogenous Rdi1p, or the addition of exogenous Rdi1p, generated stable
      cytosolic complexes. Rdi1p structure-function analysis showed that membrane
      association via the C-terminal beta-sheet domain was required for the functional
      inhibition of membrane fusion. Furthermore, Rdi1p inhibited membrane fusion
      through the binding of Rho GTPases independent from its extraction activity.

PMID- 21171964
TI  - Lipid binding to cytoglobin leads to a change in haem co-ordination: a role for
      cytoglobin in lipid signalling of oxidative stress.
AB  - Cytoglobin is a recently discovered hexa-co-ordinate haemoglobin that does not
      appear to function as a classical oxygen-binding protein. Its function is unknown
      and studies on the effects of changes in its expression have not decisively
      determined its role within the cell. In the present paper, we report that the
      protein is transformed from hexa-co-ordinate to penta-co-ordinate on binding a
      lipid molecule. This transformation occurs with the ferric oxidation state of the
      protein, but not the ferrous state, indicating that this process only occurs
      under an oxidative environment and may thus be related to redox-linked cell
      signalling mechanisms. Oleate binds to the protein in a 1:1 stoichiometry and
      with high affinity (K(d)=0.7 MUM); however, stopped-flow kinetic measurements
      yield a K(d) value of 110 MUM. The discrepancy between these K(d) values may be
      rationalized by recognizing that cytoglobin is a disulfide-linked dimer and
      invoking co-operativity in oleate binding. The lipid-induced transformation of
      cytoglobin from hexa-co-ordinate to penta-co-ordinate does not occur with similar
      hexa-co-ordinate haemoglobins such as neuroglobin, and therefore appears to be a
      unique property of cytoglobin among the haemoglobin superfamily. The lipid
      derived transformation may explain why cytoglobin has enhanced peroxidatic
      activity, converting lipids into various oxidized products, a property virtually
      absent from neuroglobin and much decreased in myoglobin. We propose that the
      binding of ferric cytoglobin to lipids and their subsequent transformation may be
      integral to the physiological function of cytoglobin, generating cell signalling
      lipid molecules under an oxidative environment.

PMID- 21171965
TI  - A functional family-wide screening of SP/KLF proteins identifies a subset of
      suppressors of KRAS-mediated cell growth.
AB  - SP/KLF (Specificity protein/Kruppel-like factor) transcription factors comprise
      an emerging group of proteins that may behave as tumour suppressors.
      Incidentally, many cancers that display alterations in certain KLF proteins are
      also associated with a high incidence of KRAS (V-Ki-ras2 Kirsten rat sarcoma
      viral oncogene homologue) mutations. Therefore in the present paper we
      investigate whether SP/KLF proteins suppress KRAS-mediated cell growth, and more
      importantly, the potential mechanisms underlying these effects. Using a
      comprehensive family-wide screening of the 24 SP/KLF members, we discovered that
      SP5, SP8, KLF2, KLF3, KLF4, KLF11, KLF13, KLF14, KLF15 and KLF16 inhibit cellular
      growth and suppress transformation mediated by oncogenic KRAS. Each protein in
      this subset of SP/KLF members individually inhibits BrdU (5-bromo-2-deoxyuridine)
      incorporation in KRAS oncogenic-mutant cancer cells. SP5, KLF3, KLF11, KLF13,
      KLF14 and KLF16 also increase apoptosis in these cells. Using KLF11 as a
      representative model for mechanistic studies, we demonstrate that this protein
      inhibits the ability of cancer cells to form both colonies in soft agar and
      tumour growth in vivo. Molecular studies demonstrate that these effects of KLF11
      are mediated, at least in part, through silencing cyclin A via binding to its
      promoter and leading to cell-cycle arrest in S-phase. Interestingly, similar to
      KLF11, KLF14 and KLF16 mechanistically share the ability to modulate the
      expression of cyclin A. Collectively, the present study stringently defines a
      distinct subset of SP/KLF proteins that impairs KRAS-mediated cell growth, and
      that mechanistically some members of this subset accomplish this, at least in
      part, through regulation of the cyclin A promoter.

PMID- 21171967
TI  - Checklists in the operating room: Help or hurdle? A qualitative study on health
      workers' experiences.
AB  - BACKGROUND: Checklists have been used extensively as a cognitive aid in aviation;
      now, they are being introduced in many areas of medicine. Although few would
      dispute the positive effects of checklists, little is known about the process of
      introducing this tool into the health care environment. In 2008, a pre-induction
      checklist was implemented in our anaesthetic department; in this study, we
      explored the nurses' and physicians' acceptance and experiences with this
      checklist. METHOD: Focus group interviews were conducted with a purposeful sample
      of checklist users (nurses and physicians) from the Department of Anaesthesia and
      Intensive Care in a tertiary teaching hospital. The interviews were analysed
      qualitatively using systematic text condensation. RESULTS: Users reported that
      checklist use could divert attention away from the patient and that it influenced
      workflow and doctor-nurse cooperation. They described senior consultants as both
      sceptical and supportive; a head physician with a positive attitude was
      considered crucial for successful implementation. The checklist improved
      confidence in unfamiliar contexts and was used in some situations for which it
      was not intended. It also revealed insufficient equipment standardisation.
      CONCLUSION: Our findings suggest several issues and actions that may be important
      to consider during checklist use and implementation.

PMID- 21171966
TI  - Mouse DNA contamination in human tissue tested for XMRV.
AB  - BACKGROUND: We used a PCR-based approach to study the prevalence of genetic
      sequences related to a gammaretrovirus, xenotropic murine leukemia virus-related
      virus, XMRV, in human prostate cancer. This virus has been identified in the US
      in prostate cancer patients and in those with chronic fatigue syndrome. However,
      with the exception of two patients in Germany, XMRV has not been identified in
      prostate cancer tissue in Europe. Most putative associations of new or old human
      retroviruses with diseases have turned out to be due to contamination. We have
      looked for XMRV sequences in DNA extracted from formalin-fixed paraffin- embedded
      prostate tissues. To control for contamination, PCR assays to detect either mouse
      mitochondrial DNA (mtDNA) or intracisternal A particle (IAP) long terminal repeat
      DNA were run on all samples, owing to their very high copy number in mouse cells.
      RESULTS: In general agreement with the US prevalence, XMRV-like sequences were
      found in 4.8% of prostate cancers. However, these were also positive, as were
      21.5% of XMRV-negative cases, for IAP sequences, and many, but not all were
      positive for mtDNA sequences. CONCLUSIONS: These results show that contamination
      with mouse DNA is widespread and detectable by the highly sensitive IAP assay,
      but not always with less sensitive assays, such as murine mtDNA PCR. This study
      highlights the ubiquitous presence of mouse DNA in laboratory specimens and
      offers a means of rigorous validation for future studies of murine retroviruses
      in human disease.

PMID- 21171969
TI  - Geographical distribution of American cutaneous leishmaniasis and its
      phlebotomine vectors (Diptera: Psychodidae) in the state of Sao Paulo, Brazil.
AB  - BACKGROUND: American cutaneous leishmaniasis (ACL) is a re-emerging disease in
      the state of Sao Paulo, Brazil. It is important to understand both the vector and
      disease distribution to help design control strategies. As an initial step in
      applying geographic information systems (GIS) and remote sensing (RS) tools to
      map disease-risk, the objectives of the present work were to: (i) produce a
      single database of species distributions of the sand fly vectors in the state of
      Sao Paulo, (ii) create combined distributional maps of both the incidence of ACL
      and its sand fly vectors, and (iii) thereby provide individual municipalities
      with a source of reference material for work carried out in their area. RESULTS:
      A database containing 910 individual records of sand fly occurrence in the state
      of Sao Paulo, from 37 different sources, was compiled. These records date from
      between 1943 to 2009, and describe the presence of at least one of the six
      incriminated or suspected sand fly vector species in 183/645 (28.4%)
      municipalities. For the remaining 462 (71.6%) municipalities, we were unable to
      locate records of any of the six incriminated or suspected sand fly vector
      species (Nyssomyia intermedia, N. neivai, N. whitmani, Pintomyia fischeri, P.
      pessoai and Migonemyia migonei). The distribution of each of the six incriminated
      or suspected vector species of ACL in the state of Sao Paulo were individually
      mapped and overlaid on the incidence of ACL for the period 1993 to 1995 and 1998
      to 2007. Overall, the maps reveal that the six sand fly vector species analyzed
      have unique and heterogeneous, although often overlapping, distributions. Several
      sand fly species - Nyssomyia intermedia and N. neivai - are highly localized,
      while the other sand fly species - N. whitmani, M. migonei, P. fischeri and P.
      pessoai - are much more broadly distributed. ACL has been reported in 160/183
      (87.4%) of the municipalities with records for at least one of the six
      incriminated or suspected sand fly vector species, while there are no records of
      any of these sand fly species in 318/478 (66.5%) municipalities with ACL.
      CONCLUSIONS: The maps produced in this work provide basic data on the
      distribution of the six incriminated or suspected sand fly vectors of ACL in the
      state of Sao Paulo, and highlight the complex and geographically heterogeneous
      pattern of ACL transmission in the region. Further studies are required to
      clarify the role of each of the six suspected sand fly vector species in
      different regions of the state of Sao Paulo, especially in the majority of
      municipalities where ACL is present but sand fly vectors have not yet been
      identified.

PMID- 21171968
TI  - Inhibiting adenoid cystic carcinoma cells growth and metastasis by blocking the
      expression of ADAM 10 using RNA interference.
AB  - BACKGROUND: Adenoid cystic carcinoma is one of the most common types of salivary
      gland cancers. The poor long-term prognosis for patients with adenoid cystic
      carcinoma is mainly due to local recurrence and distant metastasis. Disintegrin
      and metalloprotease 10 (ADAM 10) is a transmembrane protein associated with
      metastasis in a number of diverse of cancers. The aim of this study was to
      analyze the relationship between ADAM 10 and the invasive and metastatic
      potentials as well as the proliferation capability of adenoid cystic carcinoma
      cells in vitro and in vivo. METHODS: Immunohistochemistry and Western blot
      analysis were applied to detect ADAM 10 expression levels in metastatic cancer
      tissues, corresponding primary adenoid cystic carcinoma tissues, adenoid cystic
      carcinoma cell lines with high metastatic potential, and adenoid cystic carcinoma
      cell lines with low metastatic potential. RNA interference was used to knockdown
      ADAM 10 expression in adenoid cystic carcinoma cell lines with high metastatic
      potential. Furthermore, the invasive and metastatic potentials as well as the
      proliferation capability of the treated cells were observed in vitro and in vivo.
      RESULTS: It was observed that ADAM 10 was expressed at a significantly higher
      level in metastatic cancer tissues and in adenoid cystic carcinoma cell lines
      with high metastatic potential than in corresponding primary adenoid cystic
      carcinomas and adenoid cystic carcinoma cell lines with low metastatic potential.
      Additionally, silencing of ADAM 10 resulted in inhibition of cell growth and
      invasion in vitro as well as inhibition of cancer metastasis in an experimental
      murine model of lung metastases in vivo. CONCLUSIONS: These studies suggested
      that ADAM 10 plays an important role in regulating proliferation and metastasis
      of adenoid cystic carcinoma cells. ADAM 10 is potentially an important
      therapeutic target for the prevention of tumor metastases in adenoid cystic
      carcinoma.

PMID- 21171970
TI  - Mass drug administration of ivermectin in south-eastern Senegal reduces the
      survivorship of wild-caught, blood fed malaria vectors.
AB  - BACKGROUND: In south-eastern Senegal, malaria and onchocerciasis are co-endemic.
      Onchocerciasis in this region has been controlled by once or twice yearly mass
      drug administration (MDA) with ivermectin (IVM) for over fifteen years. Since
      laboratory-raised Anopheles gambiae s.s. are susceptible to ivermectin at
      concentrations found in human blood post-ingestion of IVM, it is plausible that a
      similar effect could be quantified in the field, and that IVM might have benefits
      as a malaria control tool. METHODS: In 2008 and 2009, wild-caught blood fed An.
      gambiae s.l. mosquitoes were collected from huts of three pairs of Senegalese
      villages before and after IVM MDAs. Mosquitoes were held in an insectary to
      assess their survival rate, subsequently identified to species, and their blood
      meals were identified. Differences in mosquito survival were statistically
      analysed using a Glimmix model. Lastly, changes in the daily probability of
      mosquito survivorship surrounding IVM MDAs were calculated, and these data were
      inserted into a previously developed, mosquito age-structured model of malaria
      transmission. RESULTS: Anopheles gambiae s.s. (P < 0.0001) and Anopheles
      arabiensis (P = 0.0191) from the treated villages had significantly reduced
      survival compared to those from control villages. Furthermore, An gambiae s.s.
      caught 1-6 days after MDA in treated villages had significantly reduced survival
      compared to control village collections (P = 0.0003), as well as those caught pre
      MDA (P < 0.0001) and >7 days post-MDA (P < 0.0001). The daily probability of
      mosquito survival dropped >10% for the six days following MDA. The mosquito age
      structured model of malaria transmission demonstrated that a single IVM MDA would
      reduce malaria transmission (Ro) below baseline for at least eleven days, and
      that repeated IVM MDAs would result in a sustained reduction in malaria Ro.
      CONCLUSIONS: Ivermectin MDA significantly reduced the survivorship of An. gambiae
      s.s. for six days past the date of the MDA, which is sufficient to temporarily
      reduce malaria transmission. Repeated IVM MDAs could be a novel and integrative
      malaria control tool in areas with seasonal transmission, and which would have
      simultaneous impacts on neglected tropical diseases in the same villages.

PMID- 21171971
TI  - Prevalence of adrenal masses in Japanese patients with type 2 diabetes mellitus.
AB  - INTRODUCTION: To date, there have been no reports on the prevalence of adrenal
      masses in type 2 diabetic patients. The present study aimed to evaluate the
      prevalence of adrenal incidentaloma in type 2 diabetic patients in Japan.
      SUBJECTS: We retrospectively evaluated the presence of adrenal masses using
      abdominal CT scans in 304 type 2 diabetic patients. In those with adrenal masses,
      we examined the hormone production capacity of the adrenal mass. RESULTS:
      Fourteen patients (4.6%) had an adrenal mass. Hormonal analysis identified one
      case as having subclinical Cushing's syndrome, two with primary aldosteronism.
      Eleven cases had non-functioning masses. DISCUSSION: The reported prevalence of
      adrenal incidentaloma in normal subjects is 0.6-4.0% in abdominal CT scan series.
      Our results show a relatively high prevalence of adrenal tumors in diabetic
      patients. On the other hand, the frequency of functional adenoma in diabetic
      patients is 21.4%, which is similar to that of normal subjects. CONCLUSION:
      Although further studies are needed to evaluate the prevalence of adrenal tumors
      in diabetic patients, our data suggest that evaluation of the presence of adrenal
      masses may be needed in patients with type 2 diabetes mellitus.

PMID- 21171972
TI  - Dynamics of neuroinflammation in the macrosphere model of arterio-arterial
      embolic focal ischemia: an approximation to human stroke patterns.
AB  - BACKGROUND: Neuroinflammation evolves as a multi-facetted response to focal
      cerebral ischemia. It involves activation of resident glia cell populations,
      recruitment of blood-derived leucocytes as well as humoral responses. Among these
      processes, phagocyte accumulation has been suggested to be a surrogate marker of
      neuroinflammation. We previously assessed phagocyte accumulation in human stroke
      by MRI. We hypothesize that phagocyte accumulation in the macrosphere model may
      resemble the temporal and spatial patterns observed in human stroke. METHODS: In
      a rat model of permanent focal ischemia by embolisation of TiO2-spheres we
      assessed key features of post-ischemic neuroinflammation by the means of
      histology, immunocytochemistry of glial activation and influx of hematogeneous
      cells, and quantitative PCR of TNF-alpha, IL-1, IL-18, and iNOS mRNA. RESULTS: In
      the boundary zone of the infarct, a transition of ramified microglia into ameboid
      phagocytic microglia was accompanied by an up-regulation of MHC class II on the
      cells after 3 days. By day 7, a hypercellular infiltrate consisting of activated
      microglia and phagocytic cells formed a thick rim around the ischemic infarct
      core. Interestingly, in the ischemic core microglia could only be observed at day
      7. TNF-alpha was induced rapidly within hours, IL-1beta and iNOS peaked within
      days, and IL-18 later at around 1 week after ischemia. CONCLUSIONS: The
      macrosphere model closely resembles the characteristical dynamics of postischemic
      inflammation previously observed in human stroke. We therefore suggest that the
      macrosphere model is highly appropriate for studying the pathophysiology of
      stroke in a translational approach from rodent to human.

PMID- 21171973
TI  - Contamination of human DNA samples with mouse DNA can lead to false detection of
      XMRV-like sequences.
AB  - BACKGROUND: In 2006, a novel gammaretrovirus, XMRV (xenotropic murine leukemia
      virus-related virus), was discovered in some prostate tumors. A more recent study
      indicated that this infectious retrovirus can be detected in 67% of patients
      suffering from chronic fatigue syndrome (CFS), but only very few healthy controls
      (4%). However, several groups have published to date that they could not identify
      XMRV RNA or DNA sequences in other cohorts of CFS patients, while another group
      detected murine leukemia virus (MLV)-like sequences in 87% of such patients, but
      only 7% of healthy controls. Since there is a high degree of similarity between
      XMRV and abundant endogenous MLV proviruses, it is important to distinguish
      contaminating mouse sequences from true infections. RESULTS: DNA from the
      peripheral blood of 112 CFS patients and 36 healthy controls was tested for XMRV
      with two different PCR assays. A TaqMan qPCR assay specific for XMRV pol
      sequences was able to detect viral DNA from 2 XMRV-infected cells (~ 10-12 pg
      DNA) in up to 5 MUg of human genomic DNA, but yielded negative results in the
      test of 600 ng genomic DNA from 100,000 peripheral blood cells of all samples
      tested. However, positive results were obtained with some of these samples, using
      a less specific nested PCR assay for a different XMRV sequence. DNA sequencing of
      the PCR products revealed a wide variety of virus-related sequences, some
      identical to those found in prostate cancer and CFS patients, others more closely
      related to known endogenous MLVs. However, all samples that tested positive for
      XMRV and/or MLV DNA were also positive for the highly abundant intracisternal A
      type particle (IAP) long terminal repeat and most were positive for murine
      mitochondrial cytochrome oxidase sequences. No contamination was observed in any
      of the negative control samples, containing those with no DNA template, which
      were included in each assay. CONCLUSIONS: Mouse cells contain upwards of 100
      copies each of endogenous MLV DNA. Even much less than one cell's worth of DNA
      can yield a detectable product using highly sensitive PCR technology. It is,
      therefore, vital that contamination by mouse DNA be monitored with adequately
      sensitive assays in all samples tested.

PMID- 21171974
TI  - Immunoreactivity of anti-gelsolin antibodies: implications for biomarker
      validation.
AB  - BACKGROUND: Proteomic-based discovery of biomarkers for disease has recently come
      under scrutiny for a variety of issues; one prominent issue is the lack of
      orthogonal validation for biomarkers following discovery. Validation by ELISA or
      Western blot requires the use of antibodies, which for many potential biomarkers
      are under-characterized and may lead to misleading or inconclusive results.
      Gelsolin is one such biomarker candidate in HIV-associated neurocognitive
      disorders. METHODS: Samples from human (plasma and CSF), monkey (plasma),
      monocyte-derived macrophage (supernatants), and commercial gelsolin (recombinant
      and purified) were quantitated using Western blot assay and a variety of anti
      gelsolin antibodies. Plasma and CSF was used for immunoaffinity purification of
      gelsolin which was identified in eight bands by tandem mass spectrometry.
      RESULTS: Immunoreactivity of gelsolin within samples and between antibodies
      varied greatly. In several instances, multiple bands were identified
      (corresponding to different gelsolin forms) by one antibody, but not identified
      by another. Moreover, in some instances immunoreactivity depended on the source
      of gelsolin, e.g. plasma or CSF. Additionally, some smaller forms of gelsolin
      were identified by mass spectrometry but not by any antibody. Recombinant
      gelsolin was used as reference sample. CONCLUSIONS: Orthogonal validation using
      specific monoclonal or polyclonal antibodies may reject biomarker candidates from
      further studies based on misleading or even false quantitation of those proteins,
      which circulate in various forms in body fluids.

PMID- 21171975
TI  - Knowledge and Attitudes of GPs in Saxony-Anhalt concerning the Psychological
      Aspects of Bronchial Asthma: A Questionnaire Study.
AB  - Bronchial Asthma is a worldwide condition with particularly high prevalence in
      first world countries. The reasons are multifactorial but a neglected area is the
      psychological domain. It is well known that heavy emotions can trigger attacks
      and that depression negatively affects treatment outcomes. It is also known that
      personality type has a greater effect on disease prevalence than in many other
      conditions. However, many potential psychological treatments are hardly
      considered, neither in treatment guidelines nor in reviews by asthma specialists.
      Moreover, there is very little research concerning the beliefs and practices of
      doctors regarding psychological treatments. Using a questionnaire survey we
      ascertained that local GPs in Saxony-Anhalt have reasonably good knowledge about
      the psychological elements of asthma; a third consider it to be some of the
      influence (20-40% aetiology) and a further third consider it to be even more
      important than that (at least 40% total aetiology). Our GPs use psychosomatic
      counseling sometimes or usually in the areas of sport and smoking (circa 85%
      GPs), although less so regarding breathing techniques and relaxation (c40%
      usually or sometimes do this) However despite this knowledge they refer to the
      relevant clinicians very rarely (98% sometimes, usually or always refer to a
      respiratory physician compared with only 11% referring for psychological help).

PMID- 21171976
TI  - Anxiety and depression among outpatients with type 2 diabetes: A multi-centre
      study of prevalence and associated factors.
AB  - BACKGROUND: Anxiety and depression contribute to poor disease outcomes among
      individuals with diabetes. This study aimed to assess the prevalence of anxiety
      and depression and to identify their associated factors including metabolic
      components among people with type 2 diabetes. METHODS: We conducted a cross
      sectional, multi-center study in four out-patient clinics in Karachi, Pakistan.
      In all, 889 adults with type-2 diabetes were included in this study. Anxiety and
      depression were measured by using the Hospital Anxiety and Depression Scale
      (HADS). Multivariable analysis using multiple logistic regression was carried out
      to evaluate the combined effect of various factors associated with anxiety and
      depression, while adjusting for confounding variables. RESULTS: Overall, 57.9%
      (95% CI = 54.7%, 61.2%) and 43.5% (95% CI = 40.3%, 46.8%) study participants had
      anxiety and depression respectively. Factors found to be independently associated
      with anxiety were physical inactivity, having hypertension and ischemic heart
      disease. For depression, being female, of older age, having hypertension and
      ischemic heart disease were significantly associated. Metabolic components found
      to be independently associated with both anxiety and depression were systolic
      blood pressure, fasting blood glucose and fasting blood triglycerides. Body mass
      index was independently associated with depression but not with anxiety.
      CONCLUSION: This study identified that a large proportion of adults with diabetes
      had anxiety and/or depression, and identified factors associated with these
      entities. These results alert clinicians to identify and treat anxiety and
      depression as common components of diabetes care. Additional studies are needed
      to establish the directional nature of this relationship and to test
      interventions.

PMID- 21171977
TI  - Huntington's disease: a clinical review.
AB  - Huntington disease (HD) is a rare neurodegenerative disorder of the central
      nervous system characterized by unwanted choreatic movements, behavioral and
      psychiatric disturbances and dementia. Prevalence in the Caucasian population is
      estimated at 1/10,000-1/20,000. Mean age at onset of symptoms is 30-50 years. In
      some cases symptoms start before the age of 20 years with behavior disturbances
      and learning difficulties at school (Juvenile Huntington's disease; JHD). The
      classic sign is chorea that gradually spreads to all muscles. All psychomotor
      processes become severely retarded. Patients experience psychiatric symptoms and
      cognitive decline. HD is an autosomal dominant inherited disease caused by an
      elongated CAG repeat (36 repeats or more) on the short arm of chromosome 4p16.3
      in the Huntingtine gene. The longer the CAG repeat, the earlier the onset of
      disease. In cases of JHD the repeat often exceeds 55. Diagnosis is based on
      clinical symptoms and signs in an individual with a parent with proven HD, and is
      confirmed by DNA determination. Pre-manifest diagnosis should only be performed
      by multidisciplinary teams in healthy at-risk adult individuals who want to know
      whether they carry the mutation or not. Differential diagnoses include other
      causes of chorea including general internal disorders or iatrogenic disorders.
      Phenocopies (clinically diagnosed cases of HD without the genetic mutation) are
      observed. Prenatal diagnosis is possible by chorionic villus sampling or
      amniocentesis. Preimplantation diagnosis with in vitro fertilization is offered
      in several countries. There is no cure. Management should be multidisciplinary
      and is based on treating symptoms with a view to improving quality of life.
      Chorea is treated with dopamine receptor blocking or depleting agents. Medication
      and non-medical care for depression and aggressive behavior may be required. The
      progression of the disease leads to a complete dependency in daily life, which
      results in patients requiring full-time care, and finally death. The most common
      cause of death is pneumonia, followed by suicide.

PMID- 21171978
TI  - An endogenous murine leukemia viral genome contaminant in a commercial RT-PCR kit
      is amplified using standard primers for XMRV.
AB  - During pilot studies to investigate the presence of viral RNA of xenotropic
      murine leukemia virus (MLV)-related virus (XMRV) infection in sera from chronic
      fatigue syndrome (CFS) patients in Japan, a positive band was frequently detected
      at the expected product size in negative control samples when detecting a partial
      gag region of XMRV using a one-step RT-PCR kit. We suspected that the kit itself
      might have been contaminated with small traces of endogenous MLV genome or XMRV
      and attempted to evaluate the quality of the kit in two independent laboratories.
      We purchased four one-step RT-PCR kits from Invitrogen, TaKaRa, Promega and
      QIAGEN in Japan. To amplify the partial gag gene of XMRV or other MLV-related
      viruses, primer sets (419F and 1154R, and GAG-I-F and GAG-I-R) which have been
      widely used in XMRV studies were employed. The nucleotide sequences of the
      amplicons were determined and compared with deposited sequences of a polytropic
      endogenous MLV (PmERV), XMRV and endogenous MLV-related viruses derived from CFS
      patients. We found that the enzyme mixtures of the one-step RT-PCR kit from
      Invitrogen were contaminated with RNA derived from PmERV. The nucleotide sequence
      of a partial gag region of the contaminant amplified by RT-PCR was nearly
      identical (99.4% identity) to a PmERV on chromosome 7 and highly similar (96.9 to
      97.6%) to recently identified MLV-like viruses derived from CFS patients. We also
      determined the nucleotide sequence of a partial env region of the contaminant and
      found that it was almost identical (99.6%) to the PmERV. In the investigation of
      XMRV infection in patients of CFS and prostate cancer, researchers should
      prudently evaluate the test kits for the presence of endogenous MLV as well as
      XMRV genomes prior to PCR and RT-PCR tests.

PMID- 21171979
TI  - Disease-associated XMRV sequences are consistent with laboratory contamination.
AB  - BACKGROUND: Xenotropic murine leukaemia viruses (MLV-X) are endogenous
      gammaretroviruses that infect cells from many species, including humans.
      Xenotropic murine leukaemia virus-related virus (XMRV) is a retrovirus that has
      been the subject of intense debate since its detection in samples from humans
      with prostate cancer (PC) and chronic fatigue syndrome (CFS). Controversy has
      arisen from the failure of some studies to detect XMRV in PC or CFS patients and
      from inconsistent detection of XMRV in healthy controls. RESULTS: Here we
      demonstrate that Taqman PCR primers previously described as XMRV-specific can
      amplify common murine endogenous viral sequences from mouse suggesting that mouse
      DNA can contaminate patient samples and confound specific XMRV detection. To
      consider the provenance of XMRV we sequenced XMRV from the cell line 22Rv1, which
      is infected with an MLV-X that is indistinguishable from patient derived XMRV.
      Bayesian phylogenies clearly show that XMRV sequences reportedly derived from
      unlinked patients form a monophyletic clade with interspersed 22Rv1 clones
      (posterior probability >0.99). The cell line-derived sequences are ancestral to
      the patient-derived sequences (posterior probability >0.99). Furthermore, pol
      sequences apparently amplified from PC patient material (VP29 and VP184) are
      recombinants of XMRV and Moloney MLV (MoMLV) a virus with an envelope that lacks
      tropism for human cells. Considering the diversity of XMRV we show that the mean
      pairwise genetic distance among env and pol 22Rv1-derived sequences exceeds that
      of patient-associated sequences (Wilcoxon rank sum test: p = 0.005 and p < 0.001
      for pol and env, respectively). Thus XMRV sequences acquire diversity in a cell
      line but not in patient samples. These observations are difficult to reconcile
      with the hypothesis that published XMRV sequences are related by a process of
      infectious transmission. CONCLUSIONS: We provide several independent lines of
      evidence that XMRV detected by sensitive PCR methods in patient samples is the
      likely result of PCR contamination with mouse DNA and that the described clones
      of XMRV arose from the tumour cell line 22Rv1, which was probably infected with
      XMRV during xenografting in mice. We propose that XMRV might not be a genuine
      human pathogen.

PMID- 21171980
TI  - Contamination of clinical specimens with MLV-encoding nucleic acids: implications
      for XMRV and other candidate human retroviruses.
AB  - Efforts to assess the prevalence of xenotropic murine leukemia virus-related
      virus (XMRV) in patients with prostate cancer and chronic fatigue syndrome have
      relied heavily on PCR-based testing of clinical samples and have yielded widely
      divergent findings. This week in Retrovirology, reports from four independent
      research groups illustrate the extreme care needed to exclude DNA or RNA
      contamination in PCR analyses of XMRV. In addition, phylogenetic evidence
      suggesting that previously-published XMRV sequences originated from a commonly
      used prostate carcinoma cell line (22Rv1) is presented. These findings raise
      important questions regarding the provenance of XMRV and its potential connection
      to human disease.

PMID- 21171982
TI  - Five years follow-up following two or three doses of a hepatitis B vaccine in
      adolescents aged 11-15 years: a randomised controlled study.
AB  - BACKGROUND: The standard three-dose schedule of hepatitis B vaccines is
      frequently not completed, especially in adolescents. A primary study has
      confirmed the equivalence of a two-dose schedule of an Adult formulation of
      hepatitis B vaccine [Group HBV_2D] to a three-dose schedule of a Paediatric
      formulation in adolescents (11-15 years) [Group HBV_3D]. This follow-up study
      evaluated the five year persistence of antibody response and immune memory
      against the hepatitis B surface (anti-HBs) antigens five years after completion
      of primary vaccination. METHODS: A total of 234 subjects returned at the Year 5
      time point, of which 144 subjects received a challenge dose of hepatitis B
      vaccine. Blood samples were collected yearly and pre- and post-challenge dose to
      assess anti-HBs antibody concentrations. RESULTS: At the end of five years, 79.5%
      (95% confidence interval [CI]: 71.7 - 86.1) and 91.4% (95% CI: 82.3 - 96.8) of
      subjects who received the two-dose and three-dose schedules, respectively had
      anti-HBs antibody concentrations >= 10 mIU/mL. Post-challenge dose, all subjects
      had anti-HBs antibody concentration >= 10 mIU/mL and >94% subjects had anti-HBs
      antibody concentration >= 100 mIU/mL. All subjects mounted a rapid anamnestic
      response to the challenge dose. Overall, the challenge dose was well-tolerated.
      CONCLUSION: The two-dose schedule of hepatitis B vaccine confers long-term
      immunogenicity and shows evidence of immune memory for at least five years
      following vaccination. TRIAL REGISTRATION: Clinical Trials NCT00343915,
      NCT00524576.

PMID- 21171983
TI  - Do South Asian women with PCOS have poorer health-related quality of life than
      Caucasian women with PCOS? A comparative cross-sectional study.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common chronic endocrine
      disorder affecting women of reproductive age. This study aimed to compare the
      HRQoL of South Asian and white Caucasian women with PCOS, given that it is
      particularly common among women of South Asian origin and they have been shown to
      have more severe symptoms. METHODS: The Polycystic Ovary Syndrome Questionnaire
      (PCOSQ) and the Short Form-36 (SF-36) were administered in a cross-sectional
      survey to 42 South Asian and 129 Caucasian women diagnosed with PCOS recruited
      from the gynaecology outpatient clinics of two university teaching hospitals in
      Sheffield and Leeds. Additional clinical data was abstracted from medical notes.
      Normative data, collected as part of the Oxford Health and Lifestyles II survey,
      was obtained to compare SF-36 results with ethnically matched women from the
      general UK population. Using the SF-36, normative HRQoL scores for women of South
      Asian origin were lower than for Caucasian women. Given this lower baseline we
      tested whether the same relationship holds true among those with PCOS. RESULTS:
      Although HRQoL scores for women with PCOS were lower than normative data for both
      groups, South Asian women with PCOS did not have poorer HRQoL than their
      Caucasian counterparts. For both the SF-36 and PCOSQ, mean scores were broadly
      the same for both Asian and Caucasian women. For both groups, the worst two HRQoL
      domains as measured on the PCOSQ were 'infertility' and 'weight', with respective
      scores of 35.3 and 42.3 for Asian women with PCOS compared to 38.6 and 35.4 for
      Caucasian women with PCOS. The highest scoring domain for South Asian women with
      PCOS was 'menstrual problems' (55.3), indicating best health, and was the only
      statistically significant difference from Caucasian women (p = 0.01). On the SF
      36, the lowest scoring domain was 'Energy & Vitality' for Caucasian women with
      PCOS, but this was significantly higher for Asian women with PCOS (p = 0.01). The
      best health status for both groups was 'physical functioning', although this was
      significantly lower for South Asian women with PCOS (p = 0.005). Interestingly,
      only two domains differed significantly from the normative data for the Asian
      women with PCOS, while seven domains were significantly different for the
      Caucasian women with PCOS compared to their normative counterparts. CONCLUSIONS:
      The HRQoL differences that exist between South Asian and Caucasian women in the
      general population do not appear to be replicated amongst women with PCOS. PCOS
      reduces HRQoL to broadly similar levels, regardless of ethnicity and differences
      in the normative baseline HRQoL of these groups.

PMID- 21171984
TI  - Epidemiology of rotavirus infection among young children with acute diarrhoea in
      Burkina Faso.
AB  - BACKGROUND: In anticipation of vaccine introduction, we assessed epidemiology of
      rotavirus disease among children visiting medical centre due to acute diarrhoea
      in Ouagadougou, Burkina Faso. METHODS: Between November 2008 and February 2010,
      stool specimens from 447 children less than 5 years of age suffering from
      diarrhoea were tested for the presence of rotavirus by antigen detection using an
      immunochromatographic test. Sociodemographic, environmental and clinical factors
      were assessed during the study. RESULTS: Rotavirus antigen was detected in 151
      (33.8%) of the patients. Most of the cases (94.2%) were in children < 24 months
      of age. Fever and vomiting were the symptoms most commonly reported in
      association with rotavirus diarrhoea and the patients were often hospitalized.
      Rotavirus-associated diarrhoea occurred mostly during the season from December to
      April (dry season). Rotavirus infection was significantly less frequent in breast
      fed than among bottle-fed babies. CONCLUSIONS: The results of this study
      underscore the need to control rotavirus infections among young children in
      Burkina Faso and may argue a decision on the introduction of rotavirus vaccine in
      Burkina Faso.

PMID- 21171985
TI  - Increased plasma soluble endoglin levels as an indicator of cardiovascular
      alterations in hypertensive and diabetic patients.
AB  - BACKGROUND: Endoglin is involved in the regulation of endothelial function, but
      there are no studies concerning its relation with hypertension- and diabetes
      associated pathologies. Thus, we studied the relationship between plasma levels
      of soluble endoglin and cardiovascular alterations associated with hypertension
      and diabetes. METHODS: We analyzed 288 patients: 64 with type 2 diabetes, 159
      with hypertension and 65 healthy patients. We assessed the relationship of
      soluble endoglin plasma levels measured by enzyme-linked immunosorbent assay with
      basal glycemia, glycosylated hemoglobin, blood pressure, endothelial dysfunction
      (assessed by pressure wave velocity), hypertensive retinopathy (by Keith-Wagener
      classification), left ventricular hypertrophy (by Cornell and Sokolow indexes),
      cardiovascular risk and target organ (heart, vascular, kidney) damage. RESULTS:
      There are significant correlations between endoglin and glycemia, systolic blood
      pressure, pulse pressure, pressure wave velocity and electrocardiographically
      assessed left ventricular hypertrophy. Endoglin levels were significantly higher
      in patients with diabetes who had nondipper and extreme dipper circadian blood
      pressure patterns than in dipper circadian patterns, in patients with
      hypertension and diabetes who had riser pattern than in the other patients, and
      in patients with diabetes but not hypertension who had extreme dipper pattern
      than in dipper, nondipper and riser groups. There was also a significant
      correlation between plasma-soluble endoglin and lower levels of systolic night
      day ratio. Higher endoglin levels were found in patients with diabetes who had
      retinopathy, in patients with diabetes who had a high probability of 10-year
      cardiovascular risk, and in patients with diabetes and hypertension who had three
      or more damaged target organs (heart, vessels, kidney) than in those with no
      organs affected. CONCLUSIONS: This study shows that endoglin is an indicator of
      hypertension- and diabetes-associated vascular pathologies as endothelial
      dysfunction and cardiovascular damage.

PMID- 21171986
TI  - Campylobacter jejuni isolates in Finnish patients differ according to the origin
      of infection.
AB  - BACKGROUND: Campylobacter jejuni is a significant cause of bacterial enteritis
      worldwide. Very little is known about the pathogenicity mechanisms and virulence
      factors of this important enteropathogen. C. jejuni isolates from 166 Finnish
      patients, collected from July to December in 2006, were studied for the presence
      of putative virulence factors and susceptibility to antimicrobials. Isolates were
      tested for production of gamma-glutamyltransferase (GGT) as well as the presence
      of genes ceuE, cgtB, ciaB, cj0486, pldA, virB11, wlaN, and the gene cluster
      cdtABC. Bacterial characteristics were compared to information on foreign travel
      history as well as information on the course and the symptoms of disease obtained
      from questionnaires returned by patients. RESULTS: Except for one domestic
      isolate, antimicrobial resistance was only detected in isolates of foreign
      origin. Univariate analyses showed association between bloody stools and both GGT
      production (p = 0.025) and the presence of cgtB (p = 0.034). Multivariate
      analysis verified that GGT production was more prevalent in domestic isolates (p
      < 0.0001), while the genes cj0486 (p < 0.0001) and ceuE (p < 0.0001) were
      associated with C. jejuni isolates of foreign origin. CONCLUSIONS: The results
      indicate that imported and domestic C. jejuni isolates differ significantly in
      several aspects from each other.

PMID- 21171981
TI  - Passive smoking in babies: the BIBE study (Brief Intervention in babies.
      Effectiveness).
AB  - BACKGROUND: There is evidence that exposure to passive smoking in general, and in
      babies in particular, is an important cause of morbimortality. Passive smoking is
      related to an increased risk of pediatric diseases such as sudden death syndrome,
      acute respiratory diseases, worsening of asthma, acute-chronic middle ear disease
      and slowing of lung growth.The objective of this article is to describe the BIBE
      study protocol. The BIBE study aims to determine the effectiveness of a brief
      intervention within the context of Primary Care, directed to mothers and fathers
      that smoke, in order to reduce the exposure of babies to passive smoking (ETS).
      METHODS/DESIGN: Cluster randomized field trial (control and intervention group),
      multicentric and open. SUBJECT: Fathers and/or mothers who are smokers and their
      babies (under 18 months) that attend pediatric services in Primary Care in
      Catalonia.The measurements will be taken at three points in time, in each of the
      fathers and/or mothers who respond to a questionnaire regarding their baby's
      clinical background and characteristics of the baby's exposure, together with
      variables related to the parents' tobacco consumption. A hair sample of the baby
      will be taken at the beginning of the study and at six months after the initial
      visit (biological determination of nicotine). The intervention group will apply a
      brief intervention in passive smoking after specific training and the control
      group will apply the habitual care. DISCUSSION: Exposure to ETS is an avoidable
      factor related to infant morbimortality. Interventions to reduce exposure to ETS
      in babies are potentially beneficial for their health.The BIBE study evaluates an
      intervention to reduce exposure to ETS that takes advantage of pediatric visits.
      Interventions in the form of advice, conducted by pediatric professionals, are an
      excellent opportunity for prevention and protection of infants against the
      harmful effects of ETS. TRIAL REGISTRATION: Clinical Trials.gov Identifier:
      NCT00788996.

PMID- 21171987
TI  - qPCR in gastrointestinal stromal tumors: Evaluation of reference genes and
      expression analysis of KIT and the alternative receptor tyrosine kinases FLT3,
      CSF1-R, PDGFRB, MET and AXL.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GIST) represent the most common
      mesenchymal tumors of the gastrointestinal tract. About 85% carry an activating
      mutation in the KIT or PDGFRA gene. Approximately 10% of GIST are so-called wild
      type GIST (wt-GIST) without mutations in the hot spots. In the present study we
      evaluated appropriate reference genes for the expression analysis of formalin
      fixed, paraffin-embedded and fresh frozen samples from gastrointestinal stromal
      tumors. We evaluated the gene expression of KIT as well as of the alternative
      receptor tyrosine kinase genes FLT3, CSF1-R, PDGFRB, AXL and MET by qPCR. wt-GIST
      were compared to samples with mutations in KIT exon 9 and 11 and PDGFRA exon 18
      in order to evaluate whether overexpression of these alternative RTK might
      contribute to the pathogenesis of wt-GIST. RESULTS: Gene expression variability
      of the pooled cDNA samples is much lower than the single reverse transcription
      cDNA synthesis. By combining the lowest variability values of fixed and fresh
      tissue, the genes POLR2A, PPIA, RPLPO and TFRC were chosen for further analysis
      of the GIST samples. Overexpression of KIT compared to the corresponding normal
      tissue was detected in each GIST subgroup except in GIST with PDGFRA exon 18
      mutation. Comparing our sample groups, no significant differences in the gene
      expression levels of FLT3, CSF1R and AXL were determined. An exception was the
      sample group with KIT exon 9 mutation. A significantly reduced expression of
      CSF1R, FLT3 and PDGFRB compared to the normal tissue was detected. GIST with
      mutations in KIT exon 9 and 11 and in PDGFRA exon 18 showed a significant PDGFRB
      downregulation. CONCLUSIONS: As the variability of expression levels for the
      reference genes is very high comparing fresh frozen and formalin-fixed tissue
      there is a strong need for validation in each tissue type. None of the
      alternative receptor tyrosine kinases analyzed is associated with the
      pathogenesis of wild-type or mutated GIST. It remains to be clarified whether an
      autocrine or paracrine mechanism by overexpression of receptor tyrosine kinase
      ligands is responsible for the tumorigenesis of wt-GIST.

PMID- 21171988
TI  - miRNeye: a microRNA expression atlas of the mouse eye.
AB  - BACKGROUND: MicroRNAs (miRNAs) are key regulators of biological processes. To
      define miRNA function in the eye, it is essential to determine a high-resolution
      profile of their spatial and temporal distribution. RESULTS: In this report, we
      present the first comprehensive survey of miRNA expression in ocular tissues,
      using both microarray and RNA in situ hybridization (ISH) procedures. We
      initially determined the expression profiles of miRNAs in the retina, lens,
      cornea and retinal pigment epithelium of the adult mouse eye by microarray. Each
      tissue exhibited notably distinct miRNA enrichment patterns and cluster analysis
      identified groups of miRNAs that showed predominant expression in specific ocular
      tissues or combinations of them. Next, we performed RNA ISH for over 220 miRNAs,
      including those showing the highest expression levels by microarray, and
      generated a high-resolution expression atlas of miRNAs in the developing and
      adult wild-type mouse eye, which is accessible in the form of a publicly
      available web database. We found that 122 miRNAs displayed restricted expression
      domains in the eye at different developmental stages, with the majority of them
      expressed in one or more cell layers of the neural retina. CONCLUSIONS: This
      analysis revealed miRNAs with differential expression in ocular tissues and
      provided a detailed atlas of their tissue-specific distribution during
      development of the murine eye. The combination of the two approaches offers a
      valuable resource to decipher the contributions of specific miRNAs and miRNA
      clusters to the development of distinct ocular structures.

PMID- 21171989
TI  - The provision of out-of-hours care and associated costs in an urban area of
      Switzerland: a cost description study.
AB  - BACKGROUND: In Switzerland, General Practitioners (GPs) play an important role
      for out-of-hours emergency care as one service option beside freely accessible
      and costly emergency departments of hospitals. The aim of this study was to
      evaluate the services provided and the economic consequences of a Swiss GP out-of
      hours service. METHODS: GPs participating in the out-of-hours service in the city
      of Zurich collected data on medical problems (ICPC coding), mode of contact, mode
      of resource use and services provided (time units; diagnostics; treatments). From
      a health care insurance perspective, we assessed the association between total
      costs and its two components (basic costs: charges for time units and emergency
      surcharge; individual costs: charges for clinical examination, diagnostics and
      treatment in the discretion of the GP). RESULTS: 125 GPs collected data on 685
      patient contacts. The most prevalent health problems were of respiratory (24%),
      musculoskeletal (13%) and digestive origin (12%). Home visits (61%) were the most
      common contact mode, followed by practice (25%) and telephone contacts (14%). 82%
      of patients could be treated by ambulatory care. In 20% of patients additional
      technical diagnostics, most often laboratory tests, were used. The mean total
      costs for one emergency patient contact were ?144 (95%-CI: 137-151). The mode of
      contact was an important determinant of total costs (mean total costs for home
      visits: ?176 [95%-CI: 168-184]; practice contact: ?90 [95%-CI: 84-98]; telephone
      contact: ?48 [95%-CI: 40-55]). Basic costs contributed 83% of total costs for
      home visits and 70% of total costs for practice contacts. Individual mean costs
      were similarly low for home visits (?30) and practice contacts (?27). Medical
      problems had no relevant influence on this cost pattern. CONCLUSIONS: GPs managed
      most emergency demand in their out-of-hours service by ambulatory care. They
      applied little diagnostic testing and basic care. Our findings are of relevance
      for policy makers even from other countries with different pricing policies.
      Policy makers should be interested in a reimbursement system promoting out-of
      hours care run by GPs as one valuable service option.

PMID- 21171990
TI  - Risk perception and priority setting for intervention among hepatitis C virus and
      environmental risks: a cross-sectional survey in the Cairo community.
AB  - BACKGROUND: Hepatitis C virus (HCV) recently emerged as a major public health
      hazard in Egypt. However, dramatic healthcare budget constraints limit access to
      the costly treatment. We assessed risk perception and priority setting for
      intervention among HCV, unsafe water, and outdoor air pollution in Cairo city.
      METHODS: A survey was conducted in the homes of a representative sample of
      household heads in Cairo city. Risk perception was assessed using the
      "psychometric paradigm" where health hazards are evaluated according to several
      attributes and then summarized by principal component analysis. Priority setting
      was assessed by individual ranking of interventions reducing health hazards by
      50% over five years. The Condorcet method was used to aggregate individual
      rankings of the three interventions (main study) or two of three interventions
      (validation study). Explanatory factors of priority setting were explored in
      multivariate generalized logistic models. RESULTS: HCV was perceived as having
      the most severe consequences in terms of illness and out-of-pocket costs, while
      outdoor air pollution was perceived as the most uncontrollable risk. In the main
      study (n = 2,603), improved water supply received higher priority than both
      improved outdoor air quality (60.1%, P < .0001) and screening and treatment of
      chronic hepatitis C (66.3%, P < .0001), as confirmed in the validation study (n =
      1,019). Higher education, report of HCV-related diseases in the household, and
      perception of HCV as the most severe risk were significantly associated to
      setting HCV treatment as the first priority. CONCLUSIONS: The Cairo community
      prefers to further improving water supply as compared to improved outdoor air
      quality and screening and treatment of chronic hepatitis C.

PMID- 21171991
TI  - Outcome of severe lactic acidosis associated with metformin accumulation.
AB  - INTRODUCTION: Metformin associated lactic acidosis (MALA) may complicate
      metformin therapy, particularly if metformin accumulates due to renal
      dysfunction. Profound lactic acidosis (LA) generally predicts poor outcome. We
      aimed to determine if MALA differs in outcome from LA of other origin (LAOO).
      METHODS: We conducted a retrospective analysis of all patients admitted with LA
      to our medical ICU of a tertiary referral center during a 5-year period. MALA
      patients and LAOO patients were compared with respect to parameters of acid-base
      balance, serum creatinine, hospital outcome, Simplified Acute Physiology Score II
      (SAPS II) and Sequential Organ Failure Assessment (SOFA) score, using Pearson's
      Chi-square or the Mann-Whitney U-test. RESULTS: Of 197 patients admitted with LA,
      10 had been diagnosed with MALA. With MALA, median arterial blood pH was
      significantly lower (6.78 [range 6.5 to 6.94]) and serum lactate significantly
      higher (18.7 +/- 5.3 mmol/L) than with LAOO (pH 7.20 [range 6.46 to 7.35], mean
      serum lactate 11.2 +/- 6.1 mmol/L). Overall mortality, however, was comparable
      (MALA 50%, LAOO 74%). Furthermore, survival of patients with arterial blood pH <
      7.00 (N = 41) was significantly better (50% vs. 0%) if MALA (N = 10) was the
      underlying condition compared to LAOO (N = 31). CONCLUSIONS: Compared to
      similarly severe lactic acidosis of other origin, the prognosis of MALA is
      significantly better. MALA should be considered in metformin-treated patients
      presenting with lactic acidosis.

PMID- 21171992
TI  - High levels of T lymphocyte activation in Leishmania-HIV-1 co-infected
      individuals despite low HIV viral load.
AB  - BACKGROUND: Concomitant infections may influence HIV progression by causing
      chronic activation leading to decline in T-cell function. In the Americas,
      visceral (AVL) and tegumentary leishmaniasis (ATL) have emerged as important
      opportunistic infections in HIV-AIDS patients and both of those diseases have
      been implicated as potentially important co-factors in disease progression. We
      investigated whether leishmaniasis increases lymphocyte activation in HIV-1 co
      infected patients. This might contribute to impaired cellular immune function.
      METHODS: To address this issue we analyzed CD4+ T absolute counts and the
      proportion of CD8+ T cells expressing CD38 in Leishmania/HIV co-infected patients
      that recovered after anti-leishmanial therapy. RESULTS: We found that, despite
      clinical remission of leishmaniasis, AVL co-infected patients presented a more
      severe immunossupression as suggested by CD4+ T cell counts under 200 cells/mm3,
      differing from ATL/HIV-AIDS cases that tends to show higher lymphocytes levels
      (over 350 cells/mm3). Furthermore, five out of nine, AVL/HIV-AIDS presented low
      CD4+ T cell counts in spite of low or undetectable viral load. Expression of CD38
      on CD8+ T lymphocytes was significantly higher in AVL or ATL/HIV-AIDS cases
      compared to HIV/AIDS patients without leishmaniasis or healthy subjects.
      CONCLUSIONS: Leishmania infection can increase the degree of immune system
      activation in individuals concomitantly infected with HIV. In addition, AVL/HIV
      AIDS patients can present low CD4+ T cell counts and higher proportion of
      activated T lymphocytes even when HIV viral load is suppressed under HAART. This
      fact can cause a misinterpretation of these laboratorial markers in co-infected
      patients.

PMID- 21171993
TI  - Common NFKBIL2 polymorphisms and susceptibility to pneumococcal disease: a
      genetic association study.
AB  - INTRODUCTION: Streptococcus pneumoniae remains a major global health problem and
      a leading cause of death in children worldwide. The factors that influence
      development of pneumococcal sepsis remain poorly understood, although increasing
      evidence points towards a role for genetic variation in the host's immune
      response. Recent insights from the study of animal models, rare human primary
      immunodeficiency states, and population-based genetic epidemiology have focused
      attention on the role of the proinflammatory transcription factor NF-kappaB in
      pneumococcal disease pathogenesis. The possible role of genetic variation in the
      atypical NF-kappaB inhibitor IkappaB-R, encoded by NFKBIL2, in susceptibility to
      invasive pneumococcal disease has not, to our knowledge, previously been reported
      upon. METHODS: An association study was performed examining the frequencies of
      nine common NFKBIL2 polymorphisms in two invasive pneumococcal disease case
      control groups: European individuals from hospitals in Oxfordshire, UK (275
      patients and 733 controls), and African individuals from Kilifi District
      Hospital, Kenya (687 patients with bacteraemia, of which 173 patients had
      pneumococcal disease, together with 550 controls). RESULTS: Five polymorphisms
      significantly associated with invasive pneumococcal disease susceptibility in the
      European study, of which two polymorphisms also associated with disease in
      African individuals. Heterozygosity at these loci was associated with protection
      from invasive pneumococcal disease (rs760477, Mantel-Haenszel 2 * 2 chi(2) =
      11.797, P = 0.0006, odds ratio = 0.67, 95% confidence interval = 0.53 to 0.84;
      rs4925858, Mantel-Haenszel 2 * 2 chi(2) = 9.104, P = 0.003, odds ratio = 0.70,
      95% confidence interval = 0.55 to 0.88). Linkage disequilibrium was more
      extensive in European individuals than in Kenyans. CONCLUSIONS: Common NFKBIL2
      polymorphisms are associated with susceptibility to invasive pneumococcal disease
      in European and African populations. These findings further highlight the
      importance of control of NF-kappaB in host defence against pneumococcal disease.

PMID- 21171994
TI  - New methods for next generation sequencing based microRNA expression profiling.
AB  - BACKGROUND: MicroRNAs are small non-coding RNA transcripts that regulate post
      transcriptional gene expression. The millions of short sequence reads generated
      by next generation sequencing technologies make this technique explicitly
      suitable for profiling of known and novel microRNAs. A modification to the small
      RNA expression kit (SREK, Ambion) library preparation method for the SOLiD
      sequencing platform is described to generate microRNA sequencing libraries that
      are compatible with the Illumina Genome Analyzer. RESULTS: High quality
      sequencing libraries can successfully be prepared from as little as 100 ng small
      RNA enriched RNA. An easy to use perl-based analysis pipeline called E-miR was
      developed to handle the sequencing data in several automated steps including data
      format conversion, 3' adapter removal, genome alignment and annotation to non
      coding RNA transcripts. The sample preparation and E-miR pipeline were used to
      identify 37 cardiac enriched microRNAs in stage 16 chicken embryos. Isomir
      expression profiles between the heart and embryo were highly correlated for all
      miRNAs suggesting that tissue or cell specific miRNA modifications do not occur.
      CONCLUSIONS: In conclusion, our alternative sample preparation method can
      successfully be applied to generate high quality miRNA sequencing libraries for
      the Illumina genome analyzer.

PMID- 21171995
TI  - Combining modularity, conservation, and interactions of proteins significantly
      increases precision and coverage of protein function prediction.
AB  - BACKGROUND: While the number of newly sequenced genomes and genes is constantly
      increasing, elucidation of their function still is a laborious and time-consuming
      task. This has led to the development of a wide range of methods for predicting
      protein functions in silico. We report on a new method that predicts function
      based on a combination of information about protein interactions, orthology, and
      the conservation of protein networks in different species. RESULTS: We show that
      aggregation of these independent sources of evidence leads to a drastic increase
      in number and quality of predictions when compared to baselines and other methods
      reported in the literature. For instance, our method generates more than 12,000
      novel protein functions for human with an estimated precision of ~76%, among
      which are 7,500 new functional annotations for 1,973 human proteins that
      previously had zero or only one function annotated. We also verified our
      predictions on a set of genes that play an important role in colorectal cancer
      (MLH1, PMS2, EPHB4 ) and could confirm more than 73% of them based on evidence in
      the literature. CONCLUSIONS: The combination of different methods into a single,
      comprehensive prediction method infers thousands of protein functions for every
      species included in the analysis at varying, yet always high levels of precision
      and very good coverage.

PMID- 21171996
TI  - Distribution of short interstitial telomere motifs in two plant genomes: putative
      origin and function.
AB  - BACKGROUND: Short interstitial telomere motifs (telo boxes) are short sequences
      identical to plant telomere repeat units. They are observed within the 5' region
      of several genes over-expressed in cycling cells. In synergy with various cis
      acting elements, these motifs participate in the activation of expression. Here,
      we have analysed the distribution of telo boxes within Arabidopsis thaliana and
      Oryza sativa genomes and their association with genes involved in the biogenesis
      of the translational apparatus. RESULTS: Our analysis showed that the
      distribution of the telo box (AAACCCTA) in different genomic regions of A.
      thaliana and O. sativa is not random. As is also the case for plant
      microsatellites, they are preferentially located in the 5' flanking regions of
      genes, mainly within the 5' UTR, and distributed as a gradient along the
      direction of transcription. As previously reported in Arabidopsis, a conserved
      topological association of telo boxes with site II or TEF cis-acting elements is
      observed in almost all promoters of genes encoding ribosomal proteins in O.
      sativa. Such a conserved promoter organization can be found in other genes
      involved in the biogenesis of the translational machinery including rRNA
      processing proteins and snoRNAs. Strikingly, the association of telo boxes with
      site II motifs or TEF boxes is conserved in promoters of genes harbouring snoRNA
      clusters nested within an intron as well as in the 5' flanking regions of non
      intronic snoRNA genes. Thus, the search for associations between telo boxes and
      site II motifs or TEF box in plant genomes could provide a useful tool for
      characterizing new cryptic RNA pol II promoters. CONCLUSIONS: The data reported
      in this work support the model previously proposed for the spreading of telo
      boxes within plant genomes and provide new insights into a putative process for
      the acquisition of microsatellites in plants. The association of telo boxes with
      site II or TEF cis-acting elements appears to be an essential feature of plant
      genes involved in the biogenesis of ribosomes and clearly indicates that most
      plant snoRNAs are RNA pol II products.

PMID- 21171997
TI  - Recent transfer of an iron-regulated gene from the plastid to the nuclear genome
      in an oceanic diatom adapted to chronic iron limitation.
AB  - BACKGROUND: Although the importance and widespread occurrence of iron limitation
      in the contemporary ocean is well documented, we still know relatively little
      about genetic adaptation of phytoplankton to these environments. Compared to its
      coastal relative Thalassiosira pseudonana, the oceanic diatom Thalassiosira
      oceanica is highly tolerant to iron limitation. The adaptation to low-iron
      conditions in T. oceanica has been attributed to a decrease in the photosynthetic
      components that are rich in iron. Genomic information on T. oceanica may shed
      light on the genetic basis of the physiological differences between the two
      species. RESULTS: The complete 141790 bp sequence of the T. oceanica chloroplast
      genome [GenBank: GU323224], assembled from massively parallel pyrosequencing
      (454) shotgun reads, revealed that the petF gene encoding for ferredoxin, which
      is localized in the chloroplast genome in T. pseudonana and other diatoms, has
      been transferred to the nucleus in T. oceanica. The iron-sulfur protein
      ferredoxin, a key element of the chloroplast electron transport chain, can be
      replaced by the iron-free flavodoxin under iron-limited growth conditions thereby
      contributing to a reduction in the cellular iron requirements. From a comparison
      to the genomic context of the T. pseudonana petF gene, the T. oceanica ortholog
      can be traced back to its chloroplast origin. The coding potential of the T.
      oceanica chloroplast genome is comparable to that of T. pseudonana and
      Phaeodactylum tricornutum, though a novel expressed ORF appears in the genomic
      region that has been subjected to rearrangements linked to the petF gene transfer
      event. CONCLUSIONS: The transfer of the petF from the cp to the nuclear genome in
      T. oceanica represents a major difference between the two closely related
      species. The ability of T. oceanica to tolerate iron limitation suggests that the
      transfer of petF from the chloroplast to the nuclear genome might have
      contributed to the ecological success of this species.

PMID- 21171998
TI  - The 'hidden' burden of malaria: cognitive impairment following infection.
AB  - BACKGROUND: The burden of post-malaria cognitive impairment is often overlooked.
      Given the large number of infections occurring worldwide, the magnitude of the
      problem is likely to be substantial. The objectives of this paper are; (i) to
      assess the evidence on post malarial cognitive impairment or impact on school
      education; (ii) to assess the possible positive impact of malaria drug
      prophylaxis on cognition; and (iii) to suggest recommendations on minimizing the
      burden of post-malarial cognitive impairment. METHODS: PUBMED and SCOPUS were
      searched for all articles with the key word 'Malaria' in the title field and
      'cognitive impairment' in any field. Google Scholar was searched for the same
      keywords anywhere in the article. The search was restricted to articles published
      in English within the last 15 years (1995-2010). After filtering of abstracts
      from the initial search, 44 papers had research evidence on this topic. RESULTS &
      DISCUSSION: Cognitive abilities and school performance were shown to be impaired
      in sub-groups of patients (with either cerebral malaria or uncomplicated malaria)
      when compared with healthy controls. Studies comparing cognitive functions before
      and after treatment for acute malarial illness continued to show significantly
      impaired school performance and cognitive abilities even after recovery. Malaria
      prophylaxis was shown to improve cognitive function and school performance in
      clinical trials when compared to placebo groups. The implications of these
      findings are discussed.

PMID- 21171999
TI  - Genomic and transcriptomic analysis of the AP2/ERF superfamily in Vitis vinifera.
AB  - BACKGROUND: The AP2/ERF protein family contains transcription factors that play a
      crucial role in plant growth and development and in response to biotic and
      abiotic stress conditions in plants. Grapevine (Vitis vinifera) is the only woody
      crop whose genome has been fully sequenced. So far, no detailed expression
      profile of AP2/ERF-like genes is available for grapevine. RESULTS: An exhaustive
      search for AP2/ERF genes was carried out on the Vitis vinifera genome and their
      expression profile was analyzed by Real-Time quantitative PCR (qRT-PCR) in
      different vegetative and reproductive tissues and under two different ripening
      stages.One hundred and forty nine sequences, containing at least one ERF domain,
      were identified. Specific clusters within the AP2 and ERF families showed
      conserved expression patterns reminiscent of other species and grapevine specific
      trends related to berry ripening. Moreover, putative targets of group IX ERFs
      were identified by co-expression and protein similarity comparisons. CONCLUSIONS:
      The grapevine genome contains an amount of AP2/ERF genes comparable to that of
      other dicot species analyzed so far. We observed an increase in the size of
      specific groups within the ERF family, probably due to recent duplication events.
      Expression analyses in different aerial tissues display common features
      previously described in other plant systems and introduce possible new roles for
      members of some ERF groups during fruit ripening. The presented analysis of
      AP2/ERF genes in grapevine provides the bases for studying the molecular
      regulation of berry development and the ripening process.

PMID- 21172001
TI  - General practitioners and carers: a questionnaire survey of attitudes, awareness
      of issues, barriers and enablers to provision of services.
AB  - BACKGROUND: Approximately one in ten of the UK population are unpaid carers
      supporting a family member or friend who could not manage without their help,
      saving the UK economy an estimated L87 billion. This role is known to sometimes
      have a negative impact on carers and to require support both informally and from
      statutory services. General practice is a first point of contact for carers but
      research investigating general practitioners' (GPs') attitudes towards carers and
      awareness of issues facing carers is rare. This study therefore aimed to identify
      GPs' attitudes, awareness of issues, and perceptions of the barriers and enablers
      to provision of services. METHODS: Using a self-completion questionnaire
      distributed at a series of workshops, this study investigates GPs' attitudes to
      carers; awareness and knowledge of carers' issues; services offered in general
      practice and barriers to supporting carers. RESULTS: Seventy eight out of a total
      of 95 GPs (82% response rate) from a variety of areas in England completed the
      questionnaires. The GPs identified time, resources and lack of knowledge as
      barriers, but only 9% agreed with the statement that there is little support they
      can offer carers. However, nine in ten GPs (89%) feel they have insufficient
      training here and approximately half of them (47%) lack confidence that they are
      meeting carers' needs. Confidence in identifying carers is also low (45%). Issues
      that GPs would look out for amongst carers include emotional and physical health
      problems and financial and isolation difficulties. GPs specifically highlighted
      educational and isolation issues for young carers. Few services were described
      that targeted carers. CONCLUSIONS: GPs recognise that they have an important role
      to play in supporting carers but would like training and support. Further
      investigation is needed both to determine how best to train and facilitate GPs
      and general practice teams in their role in supporting carers and to identify
      what carers need and want from general practice. Identifying carers' leads or
      carers' champions amongst practice staff is possibly one way forward. Given the
      proposed greater commissioning role for primary care, greater understanding here
      is particularly important.

PMID- 21172000
TI  - The genetic organisation of prokaryotic two-component system signalling pathways.
AB  - BACKGROUND: Two-component systems (TCSs) are modular and diverse signalling
      pathways, involving a stimulus-responsive transfer of phosphoryl groups from
      transmitter to partner receiver domains. TCS gene and domain organisation are
      both potentially informative regarding biological function, interaction
      partnerships and molecular mechanisms. However, there is currently little
      understanding of the relationships between domain architecture, gene organisation
      and TCS pathway structure. RESULTS: Here we classify the gene and domain
      organisation of TCS gene loci from 1405 prokaryotic replicons (>40,000 TCS
      proteins). We find that 200 bp is the most appropriate distance cut-off for
      defining whether two TCS genes are functionally linked. More than 90% of all TCS
      gene loci encode just one or two transmitter and/or receiver domains, however
      numerous other geometries exist, often with large numbers of encoded TCS domains.
      Such information provides insights into the distribution of TCS domains between
      genes, and within genes. As expected, the organisation of TCS genes and domains
      is affected by phylogeny, and plasmid-encoded TCS exhibit differences in
      organisation from their chromosomally-encoded counterparts. CONCLUSIONS: We
      provide here an overview of the genomic and genetic organisation of TCS domains,
      as a resource for further research. We also propose novel metrics that build upon
      TCS gene/domain organisation data and allow comparisons between genomic
      complements of TCSs. In particular, 'percentage orphaned TCS genes' (or
      'Dissemination') and 'percentage of complex loci' (or 'Sophistication') appear to
      be useful discriminators, and to reflect mechanistic aspects of TCS organisation
      not captured by existing metrics.

PMID- 21172002
TI  - Science, institutional archives and open access: an overview and a pilot survey
      on the Italian cancer research institutions.
AB  - BACKGROUND: The Open Archive Initiative (OAI) refers to a movement started around
      the '90 s to guarantee free access to scientific information by removing the
      barriers to research results, especially those related to the ever increasing
      journal subscription prices. This new paradigm has reshaped the scholarly
      communication system and is closely connected to the build up of institutional
      repositories (IRs) conceived to the benefit of scientists and research bodies as
      a means to keep possession of their own literary production. The IRs are high
      value tools which permit authors to gain visibility by enabling rapid access to
      scientific material (not only publications) thus increasing impact (citation
      rate) and permitting a multidimensional assessment of research findings. METHODS:
      A survey was conducted in March 2010 to mainly explore the managing system in use
      for archiving the research finding adopted by the Italian Scientific Institutes
      for Research, Hospitalization and Health Care (IRCCS) of the oncology area within
      the Italian National Health Service (Servizio Sanitario Nazionale, SSN). They
      were asked to respond to a questionnaire intended to collect data about
      institutional archives, metadata formats and posting of full-text documents. The
      enquiry concerned also the perceived role of the institutional repository DSpace
      ISS, built up by the Istituto Superiore di Sanita (ISS) and based on a XML scheme
      for encoding metadata. Such a repository aims at acting as a unique reference
      point for the biomedical information produced by the Italian research
      institutions. An in-depth analysis has also been performed on the collection of
      information material addressed to patients produced by the institutions surveyed.
      RESULTS: The survey respondents were 6 out of 9. The results reveal the use of
      different practices and standard among the institutions concerning: the type of
      documentation collected, the software adopted, the use and format of metadata and
      the conditions of accessibility to the IRs. CONCLUSIONS: The Italian research
      institutions in the field of oncology are moving the first steps towards the
      philosophy of OA. The main effort should be the implementation of common
      procedures also in order to connect scientific publications to researchers
      curricula. In this framework, an important effort is represented by the project
      of ISS aimed to set a common interface able to allow migration of data from
      partner institutions to the OA compliant repository DSpace ISS.

PMID- 21172004
TI  - Stress-induced survival strategies enable Salmonella Enteritidis to persistently
      colonize the chicken oviduct tissue and cope with antimicrobial factors in egg
      white: A hypothesis to explain a pandemic.
AB  - BACKGROUND: Egg-associated transmission to humans seems to be characteristic of
      the Salmonella serotype Enteritidis, explaining why this particular serotype has
      caused a worldwide pandemic since the mid '80s. Salmonella Enteritidis is much
      more capable to persistently colonize the laying hen reproductive tract and to
      survive in the hostile egg white, as compared to other serotypes. PRESENTATION OF
      THE HYPOTHESIS: It is hypothesized that stress-induced survival mechanisms enable
      the serotype Enteritidis to persistently colonize the oviduct without causing
      damage and excessive inflammation, and to cope with the antimicrobial compounds
      present in egg white. TESTING THE HYPOTHESIS: To test the hypothesis first of all
      Salmonella Enteritidis genes that are essential for colonization of the oviduct
      and survival in eggs need to be identified. Comparative genomics tools should be
      used to identify genes or pathogenicity islands that are present in Salmonella
      Enteritidis and not in the multiple non egg-contaminating serotypes. High
      throughput signature-tagged-mutagenesis approaches, coupled to micro-array
      detection of the genes that lead to an attenuated phenotype when mutated is
      proposed as an ideal tool to identify genes involved in oviduct colonization and
      egg white survival. Identifying the stressors and antibacterial molecules in the
      oviduct and in the egg white that limit colonization or survival of non
      Enteritidis serotypes is a second important objective that can theoretically be
      achieved using screenings of expressed oviduct cDNA libraries for their
      antibacterial activity against strains from multiple serotypes. Finally, the
      effect of contact with these stressors in the oviduct or egg white on Salmonella
      gene expression will need to be analyzed, in order to clarify whether serotype
      Enteritidis-specific regulation of certain stress-survival pathways are either or
      not present. IMPLICATIONS OF THE HYPOTHESIS: Knowledge on the pathogenesis of egg
      infections would furthermore give insights that might be extrapolated to other
      biological interactions, in which a highly specialized bacterial pathogen resists
      the host response in a specific biological niche. In addition, this info can be
      of value in developing early warning criteria to identify emerging egg-associated
      Salmonella strains and in developing safe live attenuated vaccine strains.

PMID- 21172003
TI  - End-of-life decisions in Greek intensive care units: a multicenter cohort study.
AB  - INTRODUCTION: Intensive care may prolong the dying process in patients who have
      been unresponsive to the treatment already provided. Limitation of life
      sustaining therapy, by either withholding or withdrawing support, is an ethically
      acceptable and common worldwide practice. The purpose of the present study was to
      examine the frequency, types, and rationale of limiting life support in Greek
      intensive care units (ICUs), the clinical and demographic parameters associated
      with it, and the participation of relatives in decision making. METHODS: This was
      a prospective observational study conducted in eight Greek multidisciplinary
      ICUs. We studied all consecutive ICU patients who died, excluding those who
      stayed in the ICU less than 48 hours or were brain dead. RESULTS: Three hundred
      six patients composed the study population, with a mean age of 64 years and a
      mean APACHE II score on admission of 21. Of study patients, 41% received full
      support, including unsuccessful cardiopulmonary resuscitation (CPR); 48% died
      after withholding of CPR; 8%, after withholding of other treatment modalities
      besides CPR; and 3%, after withdrawal of treatment. Patients in whom therapy was
      limited had a longer ICU (P < 0.01) and hospital (P = 0.01) length of stay, a
      lower Glasgow Coma Scale score (GCS) on admission (P < 0.01), a higher APACHE II
      score 24 hours before death (P < 0.01), and were more likely to be admitted with
      a neurologic diagnosis (P < 0.01). Patients who received full support were more
      likely to be admitted with either a cardiovascular (P = 0.02) or trauma diagnosis
      (P = 0.05) and to be surgical rather than medical (P = 0.05). The main factors
      that influenced the physician's decision were, when providing full support,
      reversibility of illness and prognostic uncertainty, whereas, when limiting
      therapy, unresponsiveness to treatment already offered, prognosis of underlying
      chronic disease, and prognosis of acute disorder. Relatives' participation in
      decision making occurred in 20% of cases and was more frequent when a decision to
      provide full support was made (P < 0.01). Advance directives were rare (1%).
      CONCLUSIONS: Limitation of life-sustaining treatment is a common phenomenon in
      the Greek ICUs studied. However, in a large majority of cases, it is equivalent
      to the withholding of CPR alone. Withholding of other therapies besides CPR and
      withdrawal of support are infrequent. Medical paternalism predominates in
      decision making.

PMID- 21172005
TI  - Trends in liver transplantation for primary biliary cirrhosis in the Netherlands
      1988-2008.
AB  - BACKGROUND: A decrease in the need for liver transplantations (LTX) in Primary
      Biliary Cirrhosis (PBC), possibly related to treatment with ursodeoxycholic acid
      (UDCA), has been reported in the USA and UK. The aim of this study was to assess
      LTX requirements in PBC over the past 20 years in the Netherlands. METHODS:
      Analysis of PBC transplant data of the Dutch Organ Transplant Registry during the
      period 1988-2008, including both absolute and proportional numbers. The
      indication for LTX was categorized as liver failure, hepatocellular carcinoma or
      poor quality of life (severe fatigue or pruritus). Data were analysed for two
      decades: 1.1.1988-31.12.1997 (1(st)) and 1.1.1998-31.12.2007 (2(nd)). The
      severity of disease was quantified using MELD scores. To fit lines which show
      trends over time we applied a linear regression model. RESULTS: A total of 110
      patients (87% women) was placed on the waiting list. 105 patients were
      transplanted (1(st): 61, 2(nd): 44), 5 (5%) died while listed. The absolute
      annual number of LTX for PBC slightly decreased during the 20 year period, the
      proportional number decreased significantly. At the time of LTX the mean age was
      53.6 yrs. (1(st): 53.4, 2(nd): 53.8), the mean MELD score 13.9 (1(st):14.5,
      2(nd):13.0). The median interval from diagnosis to LTX was 90.5 months
      (1(st):86.5, 2(nd): 93.5). 69% of patients was treated with UDCA (1(st) 38%,
      2(nd) 82%). CONCLUSIONS: Over the past 20 years the absolute number of LTX for
      PBC in the Netherlands showed a tendency to decrease whereas the proportional
      decrease was significant. There was a trend over time toward earlier
      transplantation.

PMID- 21172006
TI  - The vertebrate makorin ubiquitin ligase gene family has been shaped by large
      scale duplication and retroposition from an ancestral gonad-specific, maternal
      effect gene.
AB  - BACKGROUND: Members of the makorin (mkrn) gene family encode RING/C3H zinc finger
      proteins with U3 ubiquitin ligase activity. Although these proteins have been
      described in a variety of eukaryotes such as plants, fungi, invertebrates and
      vertebrates including human, almost nothing is known about their structural and
      functional evolution. RESULTS: Via partial sequencing of a testis cDNA library
      from the poeciliid fish Xiphophorus maculatus, we have identified a new member of
      the makorin gene family, that we called mkrn4. In addition to the already
      described mkrn1 and mkrn2, mkrn4 is the third example of a makorin gene present
      in both tetrapods and ray-finned fish. However, this gene was not detected in
      mouse and rat, suggesting its loss in the lineage leading to rodent murids. Mkrn2
      and mkrn4 are located in large ancient duplicated regions in tetrapod and fish
      genomes, suggesting the possible involvement of ancestral vertebrate-specific
      genome duplication in the formation of these genes. Intriguingly, many mkrn1 and
      mkrn2 intronless retrocopies have been detected in mammals but not in other
      vertebrates, most of them corresponding to pseudogenes. The nature and number of
      zinc fingers were found to be conserved in Mkrn1 and Mkrn2 but much more variable
      in Mkrn4, with lineage-specific differences. RT-qPCR analysis demonstrated a
      highly gonad-biased expression pattern for makorin genes in medaka and zebrafish
      (ray-finned fishes) and amphibians, but a strong relaxation of this specificity
      in birds and mammals. All three mkrn genes were maternally expressed before
      zygotic genome activation in both medaka and zebrafish early embryos. CONCLUSION:
      Our analysis demonstrates that the makorin gene family has evolved through large
      scale duplication and subsequent lineage-specific retroposition-mediated
      duplications in vertebrates. From the three major vertebrate mkrn genes, mkrn4
      shows the highest evolutionary dynamics, with lineage-specific loss of zinc
      fingers and even complete gene elimination from certain groups of vertebrates.
      Comparative expression analysis strongly suggests that the ancestral E3 ubiquitin
      ligase function of the single copy mkrn gene before duplication in vertebrates
      was gonad-specific, with maternal expression in early embryos.

PMID- 21172008
TI  - Validation of the kidney disease quality of life-short form: a cross-sectional
      study of a dialysis-targeted health measure in Singapore.
AB  - BACKGROUND: In Singapore, the prevalence of end-stage renal disease (ESRD) and
      the number of people on dialysis is increasing. The impact of ESRD on patient
      quality of life has been recognized as an important outcome measure. The Kidney
      Disease Quality Of Life-Short Form (KDQOL-SFTM) has been validated and is widely
      used as a measure of quality of life in dialysis patients in many countries, but
      not in Singapore. We aimed to determine the reliability and validity of the KDQOL
      SFTM for haemodialysis patients in Singapore. METHODS: From December 2006 through
      January 2007, this cross-sectional study gathered data on patients >=21 years
      old, who were undergoing haemodialysis at National Kidney Foundation in
      Singapore. We used exploratory factor analysis to determine construct validity of
      the eight KDQOL-SFTM sub-scales, Cronbach's alpha coefficient to determine
      internal consistency reliability, correlation of the overall health rating with
      kidney disease-targeted scales to confirm validity, and correlation of the eight
      sub-scales with age, income and education to determine convergent and divergent
      validity. RESULTS: Of 1980 haemodialysis patients, 1180 (59%) completed the KDQOL
      SFTM. Full information was available for 980 participants, with a mean age of 56
      years. The sample was representative of the total dialysis population in
      Singapore, except Indian ethnicity that was over-represented. The instrument
      designers' proposed eight sub-scales were confirmed, which together accounted for
      68.4% of the variance. All sub-scales had a Cronbach's alpha above the
      recommended minimum value of 0.7 to indicate good reliability (range: 0.72 to
      0.95), except for Social function (0.66). Correlation of items within subscales
      was higher than correlation of items outside subscales in 90% of the cases. The
      overall health rating positively correlated with kidney disease-targeted scales,
      confirming validity. General health subscales were found to have significant
      associations with age, income and education, confirming convergent and divergent
      validity. CONCLUSIONS: The psychometric properties of the KDQOL-SFTM resulting
      from this first-time administration of the instrument support the validity and
      reliability of the KDQOL-SFTM as a measure of quality of life of haemodialysis
      patients in Singapore. It is, however, necessary to determine the test-retest
      reliability of the KDQOL-SFTM among the haemodialysis population of Singapore.

PMID- 21172007
TI  - Global analysis of the eukaryotic pathways and networks regulated by Salmonella
      typhimurium in mouse intestinal infection in vivo.
AB  - BACKGROUND: Acute enteritis caused by Salmonella is a public health concern.
      Salmonella infection is also known to increase the risk of inflammatory bowel
      diseases and cancer. Therefore, it is important to understand how Salmonella
      works in targeting eukaryotic pathways in intestinal infection. However, the
      global physiological function of Salmonella typhimurium in intestinal mucosa in
      vivo is unclear. In this study, a whole genome approach combined with
      bioinformatics assays was used to investigate the in vivo genetic responses of
      the mouse colon to Salmonella. We focused on the intestinal responses in the
      early stage (8 hours) and late stage (4 days) after Salmonella infection.
      RESULTS: Of the 28,000 genes represented on the array, our analysis of mRNA
      expression in mouse colon mucosa showed that a total of 856 genes were expressed
      differentially at 8 hours post-infection. At 4 days post-infection, a total of
      7558 genes were expressed differentially. 23 differentially expressed genes from
      the microarray data was further examined by real-time PCR. Ingenuity Pathways
      Analysis identified that the most significant pathway associated with the
      differentially expressed genes in 8 hours post-infection is oxidative
      phosphorylation, which targets the mitochondria. At the late stage of infection,
      a series of pathways associated with immune and inflammatory response,
      proliferation, and apoptosis were identified, whereas the oxidative
      phosphorylation was shut off. Histology analysis confirmed the biological role of
      Salmonella, which induced a physiological state of inflammation and proliferation
      in the colon mucosa through the regulation of multiple signaling pathways. Most
      of the metabolism-related pathways were targeted by down-regulated genes, and a
      general repression process of metabolic pathways was observed. Network analysis
      supported IFN-gamma and TNF-alpha function as mediators of the
      immune/inflammatory response for host defense against pathogen. CONCLUSION: Our
      study provides novel genome-wide transcriptional profiling data on the mouse
      colon mucosa's response to the Salmonella typhimurium infection. Building the
      pathways and networks of interactions between these genes help us to understand
      the complex interplay in the mice colon during Salmonella infection, and further
      provide new insights into the molecular cascade, which is mobilized to combat
      Salmonella-associated colon infection in vivo.

PMID- 21172009
TI  - Comparison of alternative risk adjustment measures for predictive modeling: high
      risk patient case finding using Taiwan's National Health Insurance claims.
AB  - BACKGROUND: Predictive modeling presents an opportunity to contain the expansion
      of medical expenditures by focusing on very few people. Evaluation of how risk
      adjustment models perform in predictive modeling in Taiwan or Asia has been rare.
      The aims of this study were to evaluate the performance of different risk
      adjustment models (the ACG risk adjustment system and prior expenditures) in
      predictive modeling, using Taiwan's National Health Insurance (NHI) claims data,
      and to compare characteristics of potentially high-expenditure subjects
      identified through different models. METHODS: A random sample of NHI enrollees
      continuously enrolled in 2002 and 2003 (n = 164,562) was selected. Health status
      measures and total expenditures derived from 2002 NHI claims data were used to
      predict the possibility of becoming 2003 top users. Statistics-based indicators
      (C-statistics, sensitivity, & Predictive Positive Value) and characteristics of
      identified top groups by different models (expenditures and prevalence of
      manageable diseases) were presented. RESULTS: Both diagnosis-based and prior
      expenditures models performed much better than the demographic model. Diagnosis
      based models were better in identifying top users with manageable diseases; prior
      expenditures models were better in statistics-based indicators and identifying
      people with higher average expenditures. Prior expenditures status could
      correctly identify more actual top users than diagnosis-based or demographic
      models. The proportions of actual top users that could be identified by diagnosis
      based models alone were much lower than that identified by prior expenditures
      status. CONCLUSIONS: Predicted top users identified by different models have
      different characteristics and there is little agreement between modes regarding
      which groups would be potentially top users; therefore, which model to use should
      depend on the purpose of predictive modeling. Prior expenditures are a more
      powerful tool than diagnosis-based risk adjusters in terms of correctly
      identifying more actual high expenditures users. There is still much room left
      for improvement of diagnosis-based models in predictive modeling.

PMID- 21172010
TI  - c-Jun NH2-terminal kinase-dependent upregulation of DR5 mediates cooperative
      induction of apoptosis by perifosine and TRAIL.
AB  - BACKGROUND: Perifosine, an alkylphospholipid tested in phase II clinical trials,
      modulates the extrinsic apoptotic pathway and cooperates with tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL) to augment apoptosis. The
      current study focuses on revealing the mechanisms by which perifosine enhances
      TRAIL-induced apoptosis. RESULTS: The combination of perifosine and TRAIL was
      more active than each single agent alone in inducing apoptosis of head and neck
      squamous cell carcinoma cells and inhibiting the growth of xenografts.
      Interestingly, perifosine primarily increased cell surface levels of DR5 although
      it elevated the expression of both DR4 and DR5. Blockade of DR5, but not DR4
      upregulation, via small interfering RNA (siRNA) inhibited perifosine/TRAIL
      induced apoptosis. Perifosine increased phosphorylated c-Jun NH2-terminal kinase
      (JNK) and c-Jun levels, which were paralleled with DR4 and DR5 induction.
      However, only DR5 upregulaiton induced by perifosine could be abrogated by both
      the JNK inhibitor SP600125 and JNK siRNA. The antioxidants, N-acetylcysteine and
      glutathione, but not vitamin C or tiron, inhibited perifosine-induced elevation
      of p-c-Jun, DR4 and DR5. Moreover, no increased production of reactive oxygen
      species was detected in perifosine-treated cells although reduced levels of
      intracellular GSH were measured. CONCLUSIONS: DR5 induction plays a critical role
      in mediating perifosine/TRAIL-induced apoptosis. Perifosine induces DR5
      expression through a JNK-dependent mechanism independent of reactive oxygen
      species.

PMID- 21172012
TI  - Does the development of new medicinal products in the European Union address
      global and regional health concerns?
AB  - BACKGROUND: Since 1995, approval for many new medicinal products has been
      obtained through a centralized procedure in the European Union. In recent years,
      the use of summary measures of population health has become widespread. We
      investigated whether efforts to develop innovative medicines are focusing on the
      most relevant conditions from a global public health perspective. METHODS: We
      reviewed the information on new medicinal products approved by centralized
      procedure from 1995 to 2009, information that is available to the public in the
      European Commission Register of medicinal products and the European Public
      Assessment Reports from the European Medicines Agency. Morbidity and mortality
      data were included for each disease group, according to the Global Burden of
      Disease project. We evaluated the association between authorized medicinal
      products and burden of disease measures based on disability-adjusted life years
      (DALYs) in the European Union and worldwide. RESULTS: We considered 520 marketing
      authorizations for medicinal products and 338 active ingredients. New
      authorizations were seen to increase over the period analyzed. There was a
      positive, high correlation between DALYs and new medicinal product development
      (rho = 0.619, p = 0.005) in the European Union, and a moderate correlation for
      middle-low-income countries (rho = 0.497, p = 0.030) and worldwide (rho = 0.490,
      p = 0.033). The most neglected conditions at the European level (based on their
      attributable health losses) were neuropsychiatric diseases, cardiovascular
      diseases, respiratory diseases, sense organ conditions, and digestive diseases,
      while globally, they were perinatal conditions, respiratory infections, sense
      organ conditions, respiratory diseases, and digestive diseases. CONCLUSIONS: We
      find that the development of new medicinal products is higher for some diseases
      than others. Pharmaceutical industry leaders and policymakers are invited to
      consider the implications of this imbalance by establishing work plans that allow
      for the setting of future priorities from a public health perspective.

PMID- 21172011
TI  - Abnormal nociception and opiate sensitivity of STOP null mice exhibiting elevated
      levels of the endogenous alkaloid morphine.
AB  - BACKGROUND: Mice deficient for the stable tubule only peptide (STOP) display
      altered dopaminergic neurotransmission associated with severe behavioural defects
      including disorganized locomotor activity. Endogenous morphine, which is present
      in nervous tissues and synthesized from dopamine, may contribute to these
      behavioral alterations since it is thought to play a role in normal and
      pathological neurotransmission. RESULTS: In this study, we showed that STOP null
      brain structures, including cortex, hippocampus, cerebellum and spinal cord,
      contain high endogenous morphine amounts. The presence of elevated levels of
      morphine was associated with the presence of a higher density of mu opioid
      receptor with a higher affinity for morphine in STOP null brains. Interestingly,
      STOP null mice exhibited significantly lower nociceptive thresholds to thermal
      and mechanical stimulations. They also had abnormal behavioural responses to the
      administration of exogenous morphine and naloxone. Low dose of morphine (1 mg/kg,
      i.p.) produced a significant mechanical antinociception in STOP null mice whereas
      it has no effect on wild-type mice. High concentration of naloxone (1 mg/kg) was
      pronociceptive for both mice strain, a lower concentration (0.1 mg/kg) was found
      to increase the mean mechanical nociceptive threshold only in the case of STOP
      null mice. CONCLUSIONS: Together, our data show that STOP null mice displayed
      elevated levels of endogenous morphine, as well as an increase of morphine
      receptor affinity and density in brain. This was correlated with hypernociception
      and impaired pharmacological sensitivity to mu opioid receptor ligands.

PMID- 21172015
TI  - Illness costs to households are a key barrier to access diagnostic and treatment
      services for tuberculosis in Tajikistan.
AB  - BACKGROUND: Tuberculosis (TB) control is based on early detection and complete
      treatment of infectious cases. Consequently, it is important that TB suspects and
      patients can readily access medical care. This qualitative study investigated
      determinants of access to DOTS services as identified by patients, health
      providers and community members in four districts in Tajikistan. FINDINGS: Focus
      group discussions were conducted in order to investigate access to TB services. A
      conceptual framework for access to care guided the analysis. Thirteen focus group
      discussions involving a total of 97 informants were conducted. Content analysis
      of discussions and a rating to quantify the relative importance of discussed
      factors were carried out. The conceptual framework identifies five main
      components of access to which factors can be assigned: availability, adequacy,
      acceptability, accessibility and affordability.Financial factors were considered
      the most important determinants of access to diagnosis and treatment of
      tuberculosis. Expenditure for drugs and consultations, for transport, and for
      special foods as well as lost income were identified as major barriers to
      treatment. Stigma, doubts about curability and low perceived quality of care were
      not seen to be significant determinants of access to care for tuberculosis.
      Community members were well aware of symptoms of tuberculosis and of medical
      services. These findings were consistent between different respondent groups
      (community members, patients and providers). They were also highly consistent
      between the open discussion and the confidential rating. CONCLUSIONS: Illness
      costs to households were identified as the main barrier to tuberculosis diagnosis
      and treatment. To improve access and ultimately adherence to tuberculosis
      treatment, effective mitigation strategies, e.g. changes in case management, food
      contributions or financial stimuli, need to be explored and implemented.

PMID- 21172013
TI  - Expression profiling of formalin-fixed paraffin-embedded primary breast tumors
      using cancer-specific and whole genome gene panels on the DASL(r) platform.
AB  - BACKGROUND: The cDNA-mediated Annealing, extension, Selection and Ligation (DASL)
      assay has become a suitable gene expression profiling system for degraded RNA
      from paraffin-embedded tissue. We examined assay characteristics and the
      performance of the DASL 502-gene Cancer Panel v1 (1.5K) and 24,526-gene panel
      (24K) platforms at differentiating nine human epidermal growth factor receptor 2-
      positive (HER2+) and 11 HER2-negative (HER2-) paraffin-embedded breast tumors.
      METHODS: Bland-Altman plots and Spearman correlations evaluated intra/inter-panel
      agreement of normalized expression values. Unequal-variance t-statistics tested
      for differences in expression levels between HER2 + and HER2 - tumors. Regulatory
      network analysis was performed using Metacore (GeneGo Inc., St. Joseph, MI).
      RESULTS: Technical replicate correlations ranged between 0.815-0.956 and 0.986
      0.997 for the 1.5K and 24K panels, respectively. Inter-panel correlations of
      expression values for the common 498 genes across the two panels ranged between
      0.485-0.573. Inter-panel correlations of expression values of 17 probes with base
      pair sequence matches between the 1.5K and 24K panels ranged between 0.652-0.899.
      In both panels, erythroblastic leukemia viral oncogene homolog 2 (ERBB2) was the
      most differentially expressed gene between the HER2 + and HER2 - tumors and seven
      additional genes had p-values < 0.05 and log2 -fold changes > |0.5| in expression
      between HER2 + and HER2 - tumors: topoisomerase II alpha (TOP2A), cyclin a2
      (CCNA2), v-fos fbj murine osteosarcoma viral oncogene homolog (FOS), wingless
      type mmtv integration site family, member 5a (WNT5A), growth factor receptor
      bound protein 7 (GRB7), cell division cycle 2 (CDC2), and baculoviral iap repeat
      containing protein 5 (BIRC5). The top 52 discriminating probes from the 24K panel
      are enriched with genes belonging to the regulatory networks centered around v
      myc avian myelocytomatosis viral oncogene homolog (MYC), tumor protein p53
      (TP53), and estrogen receptor alpha (ESR1). Network analysis with a two-step
      extension also showed that the eight discriminating genes common to the 1.5K and
      24K panels are functionally linked together through MYC, TP53, and ESR1.
      CONCLUSIONS: The relative RNA abundance obtained from two highly differing
      density gene panels are correlated with eight common genes differentiating HER2 +
      and HER2 - breast tumors. Network analyses demonstrated biological consistency
      between the 1.5K and 24K gene panels.

PMID- 21172014
TI  - Work hours, weight status, and weight-related behaviors: a study of metro transit
      workers.
AB  - BACKGROUND: Associations between hours worked per week and Body Mass Index (BMI),
      food intake, physical activity, and perceptions of eating healthy at work were
      examined in a sample of transit workers. METHODS: Survey data were collected from
      1086 transit workers. Participants reported hours worked per week, food choices,
      leisure-time physical activity and perceptions of the work environment with
      regard to healthy eating. Height and weight were measured for each participant.
      Multivariate linear and logistic regressions were conducted to examine
      associations between work hours and behavioral variables. Associations were
      examined in the full sample and stratified by gender. RESULTS: Transit workers
      working in the highest work hour categories had higher BMI and poorer dietary
      habits, with results differing by gender. Working 50 or more hours per week was
      associated with higher BMI among men but not women. Additionally, working 50 or
      more hours per week was significantly associated with higher frequency of
      accessing cold beverage, cold food, and snack vending machines among men. Working
      40 or more hours per week was associated with higher frequency of accessing cold
      food vending machines among women. Reported frequency of fruit and vegetable
      intake was highest among women working 50 or more hours per week. Intake of
      sweets, sugar sweetened beverages, and fast food did not vary with work hours in
      men or women. Physical activity and perception of ease of eating healthy at work
      were not associated with work hours in men or women. CONCLUSIONS: Long work hours
      were associated with more frequent use of garage vending machines and higher BMI
      in transit workers, with associations found primarily among men. Long work hours
      may increase dependence upon food availability at the worksite, which highlights
      the importance of availability of healthy food choices.

PMID- 21172017
TI  - Evidences showing wide presence of small genomic aberrations in chronic
      lymphocytic leukemia.
AB  - BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia
      in the western population. Although genetic factors are considered to contribute
      to CLL etiology, at present genomic aberrations identified in CLL are limited
      compared with those identified in other types of leukemia, which raises the
      question of the degree of genetic influence on CLL. We performed a high
      resolution genome scanning study to address this issue. FINDINGS: Using the
      restriction paired-end-based Ditag Genome Scanning technique, we analyzed three
      primary CLL samples at a kilobase resolution, and further validated the results
      in eight primary CLL samples including the two used for ditag collection. From
      51,632 paired-end tags commonly detected in the three CLL samples representing 5%
      of the HindIII restriction fragments in the genomes, we identified 230 paired-end
      tags that were present in all three CLL genomes but not in multiple normal human
      genome reference sequences. Mapping the full-length sequences of the fragments
      detected by these unmapped tags in seven additional CLL samples confirmed that
      these are the genomic aberrations caused by small insertions and deletions, and
      base changes spreading across coding and non-coding regions. CONCLUSIONS: Our
      study identified hundreds of loci with insertion, deletion, base change, and
      restriction site polymorphism present in both coding and non-coding regions in
      CLL genomes, indicating the wide presence of small genomic aberrations in chronic
      lymphocytic leukemia. Our study supports the use of a whole genome sequencing
      approach for comprehensively decoding the CLL genome for better understanding of
      the genetic defects in CLL.

PMID- 21172016
TI  - A critical role for lymphatic endothelial heparan sulfate in lymph node
      metastasis.
AB  - BACKGROUND: Lymph node metastasis constitutes a key event in tumor progression.
      The molecular control of this process is poorly understood. Heparan sulfate is a
      linear polysaccharide consisting of unique sulfate-modified disaccharide repeats
      that allow the glycan to bind a variety of proteins, including chemokines. While
      some chemokines may drive lymphatic trafficking of tumor cells, the functional
      and genetic importance of heparan sulfate as a possible mediator of chemokine
      actions in lymphatic metastasis has not been reported. RESULTS: We applied a loss
      of-function genetic approach employing lymphatic endothelial conditional
      mutations in heparan sulfate biosynthesis to study the effects on tumor-lymphatic
      trafficking and lymph node metastasis. Lymphatic endothelial deficiency in N
      deacetylase/N-sulfotransferase-1 (Ndst1), a key enzyme involved in sulfating
      nascent heparan sulfate chains, resulted in altered lymph node metastasis in
      tumor-bearing gene targeted mice. This occurred in mice harboring either a pan
      endothelial Ndst1 mutation or an inducible lymphatic-endothelial specific
      mutation in Ndst1. In addition to a marked reduction in tumor metastases to the
      regional lymph nodes in mutant mice, specific immuno-localization of CCL21, a
      heparin-binding chemokine known to regulate leukocyte and possibly tumor-cell
      traffic, showed a marked reduction in its ability to associate with tumor cells
      in mutant lymph nodes. In vitro modified chemotaxis studies targeting heparan
      sulfate biosynthesis in lymphatic endothelial cells revealed that heparan sulfate
      secreted by lymphatic endothelium is required for CCL21-dependent directional
      migration of murine as well as human lung carcinoma cells toward the targeted
      lymphatic endothelium. Lymphatic heparan sulfate was also required for binding of
      CCL21 to its receptor CCR7 on tumor cells as well as the activation of migration
      signaling pathways in tumor cells exposed to lymphatic conditioned medium.
      Finally, lymphatic cell-surface heparan sulfate facilitated receptor-dependent
      binding and concentration of CCL21 on the lymphatic endothelium, thereby serving
      as a mechanism to generate lymphatic chemokine gradients. CONCLUSIONS: This work
      demonstrates the genetic importance of host lymphatic heparan sulfate in
      mediating chemokine dependent tumor-cell traffic in the lymphatic
      microenvironment. The impact on chemokine dependent lymphatic metastasis may
      guide novel therapeutic strategies.

PMID- 21172018
TI  - Text messaging: an innovative method of data collection in medical research.
AB  - BACKGROUND: The ubiquitous use of mobile phones in sending and receiving text
      messages has become a norm for young people. Undeniably, text messaging has
      become a new and important communication medium not only in the social realm but
      in education as well. The aim of this study is to evaluate the effectiveness of
      using text messaging as a means to collect data for a medical research project.A
      cross sectional study was carried out during a double blind, randomized
      controlled trial to assess the efficacy and safety of a probiotic in the
      management of Irritable Bowel Syndrome (IBS). The study aim was to assess the
      response rate of weekly symptom reports via Short Message Service (SMS). The
      subjects were undergraduates in a private medical university in Malaysia. They
      were identified through a previous university wide study as suffering from IBS
      based on Rome III criteria. The subjects were randomly assigned to either the
      treatment arm receiving a daily probiotic, or the placebo arm. They were required
      to score their symptoms using eight-item-questionnaires at baseline, and
      thereafter weekly, for a total of 8 weeks. All subjects were given the choice to
      communicate their symptom scores by text messaging via mobile phones or by email.
      SMS text messages were sent to remind trial subjects to attend face-to-face
      visits and to complete a paper based 34-item-questionnaires on IBS quality of
      life assessment at baseline and at end of 8 weeks. FINDINGS: The response rate of
      weekly symptom scores via Short Message Service (SMS) from a total of 38 subjects
      was 100%. Through the study, 342 reports were submitted: 33.3% of these were
      received on the due date without reminder, 60.0% one day after the deadline,
      after a single reminder, 6.1% 2-3 days after the deadline, after 2-3 reminders
      and 0.6% 5 days after the deadline, after SMS, phone reminder and face-to-face
      encounter. All SMS symptom reports, whether on time or late, were complete. With
      the help of SMS reminder, all trial subjects completed the paper based IBS
      quality of life assessment at baseline and at end of study. CONCLUSIONS: This
      study found using text messaging via mobile phone an excellent instrument for
      collecting weekly symptom reports in response to trial medication, reminding
      trial subjects to attend face to face visits and completing more complex paper
      based evaluation. The 100% response rate of weekly symptom reports was
      facilitated by using simple number codes for SMS submission. TRIAL REGISTRATION:
      Not appropriate.

PMID- 21172019
TI  - The colorectal cancer disease-specific transcriptome may facilitate the discovery
      of more biologically and clinically relevant information.
AB  - BACKGROUND: To date, there are no clinically reliable predictive markers of
      response to the current treatment regimens for advanced colorectal cancer. The
      aim of the current study was to compare and assess the power of transcriptional
      profiling using a generic microarray and a disease-specific transcriptome-based
      microarray. We also examined the biological and clinical relevance of the disease
      specific transcriptome. METHODS: DNA microarray profiling was carried out on
      isogenic sensitive and 5-FU-resistant HCT116 colorectal cancer cell lines using
      the Affymetrix HG-U133 Plus2.0 array and the Almac Diagnostics Colorectal cancer
      disease specific Research tool. In addition, DNA microarray profiling was also
      carried out on pre-treatment metastatic colorectal cancer biopsies using the
      colorectal cancer disease specific Research tool. The two microarray platforms
      were compared based on detection of probesets and biological information.
      RESULTS: The results demonstrated that the disease-specific transcriptome-based
      microarray was able to out-perform the generic genomic-based microarray on a
      number of levels including detection of transcripts and pathway analysis. In
      addition, the disease-specific microarray contains a high percentage of antisense
      transcripts and further analysis demonstrated that a number of these exist in
      sense:antisense pairs. Comparison between cell line models and metastatic CRC
      patient biopsies further demonstrated that a number of the identified
      sense:antisense pairs were also detected in CRC patient biopsies, suggesting
      potential clinical relevance. CONCLUSIONS: Analysis from our in vitro and
      clinical experiments has demonstrated that many transcripts exist in
      sense:antisense pairs including IGF2BP2, which may have a direct regulatory
      function in the context of colorectal cancer. While the functional relevance of
      the antisense transcripts has been established by many studies, their functional
      role is currently unclear; however, the numbers that have been detected by the
      disease-specific microarray would suggest that they may be important regulatory
      transcripts. This study has demonstrated the power of a disease-specific
      transcriptome-based approach and highlighted the potential novel biologically and
      clinically relevant information that is gained when using such a methodology.

PMID- 21172020
TI  - AAV2-mediated in vivo immune gene therapy of solid tumours.
AB  - BACKGROUND: Many strategies have been adopted to unleash the potential of gene
      therapy for cancer, involving a wide range of therapeutic genes delivered by
      various methods. Immune therapy has become one of the major strategies adopted
      for cancer gene therapy and seeks to stimulate the immune system to target tumour
      antigens. In this study, the feasibility of AAV2 mediated immunotherapy of
      growing tumours was examined, in isolation and combined with anti-angiogenic
      therapy. METHODS: Immune-competent Balb/C or C57 mice bearing subcutaneous JBS
      fibrosarcoma or Lewis Lung Carcinoma (LLC) tumour xenografts respectively were
      treated by intra-tumoural administration of AAV2 vector encoding the immune up
      regulating cytokine granulocyte macrophage-colony stimulating factor (GM-CSF) and
      the co-stimulatory molecule B7-1 to subcutaneous tumours, either alone or in
      combination with intra-muscular (IM) delivery of AAV2 vector encoding Nk4 14 days
      prior to tumour induction. Tumour growth and survival was monitored for all
      animals. Cured animals were re-challenged with tumourigenic doses of the original
      tumour type. In vivo cytotoxicity assays were used to investigate establishment
      of cell-mediated responses in treated animals. RESULTS: AAV2-mediated GM-CSF, B7
      1 treatment resulted in a significant reduction in tumour growth and an increase
      in survival in both tumour models. Cured animals were resistant to re-challenge,
      and induction of T cell mediated anti-tumour responses were demonstrated.
      Adoptive transfer of splenocytes to naive animals prevented tumour establishment.
      Systemic production of Nk4 induced by intra-muscular (IM) delivery of Nk4
      significantly reduced subcutaneous tumour growth. However, combination of Nk4
      treatment with GM-CSF, B7-1 therapy reduced the efficacy of the immune therapy.
      CONCLUSIONS: Overall, this study demonstrates the potential for in vivo AAV2
      mediated immune gene therapy, and provides data on the inter-relationship between
      tumour vasculature and immune cell recruitment.

PMID- 21172021
TI  - Impact of antigenic and genetic drift on the serologic surveillance of H5N2 avian
      influenza viruses.
AB  - BACKGROUND: Serologic surveillance of Avian Influenza (AI) viruses is carried out
      by the hemagglutination inhibition (HI) test using reference reagents. This
      method is recommended by animal health organizations as a standard test to detect
      antigenic differences (subtypes) between circulating influenza virus, vaccine-
      and/or reference- strains. However, significant discrepancies between reference
      antisera and field isolates have been observed during serosurveillance of
      influenza A viruses in pig and poultry farms. The objective of this study was to
      examine the effects of influenza virus genetic and antigenic drift on serologic
      testing using standard HI assays and reference reagents. Low pathogenic AI H5N2
      viruses isolated in Mexico between 1994 and 2008 were used for phylogenetic
      analysis of AI hemagglutinin genes and for serologic testing using antisera
      produced with year-specific AI virus isolates. RESULTS: Phylogenetic analysis
      revealed significant divergence between early LPAI H5N2 viruses (1994 - 1998) and
      more recent virus field isolates (2002 - 2008). Results of the HI test were
      markedly influenced by the selection of the AI H5N2 virus (year of isolation)
      used as reference antigen for the assay. These analyses indicate that LPAI H5N2
      viruses in Mexico are constantly undergoing genetic drift and that
      serosurveillance of AI viruses is significantly influenced by the antigen or
      antisera used for the HI test. CONCLUSIONS: Reference viral antigens and/or
      antisera need to be replaced constantly during surveillance of AI viruses to keep
      pace with the AI antigenic drift. This strategy should improve the estimation of
      antigenic differences between circulating AI viruses and the selection of
      suitable vaccine strains.

PMID- 21172022
TI  - A theoretical decision model to help inform advance directive discussions for
      patients with COPD.
AB  - BACKGROUND: Advance directives (AD) may promote preference-concordant care yet
      are absent in many patients with Chronic Obstructive Pulmonary Disease (COPD). In
      order to begin to inform AD discussions between clinicians and COPD patients, we
      constructed a decision tree to estimate the impact of alternative AD decisions on
      both quality and quantity of life (quality adjusted life years, QALYs). METHODS:
      Two aspects of the AD were considered, Do Not Intubate (DNI; i.e., no invasive
      mechanical ventilation) and Full Code (i.e., may use invasive mechanical
      ventilation). Model parameters were based on published estimates. Our model
      follows hypothetical patients with COPD to evaluate the effect of underlying COPD
      severity and of hypothetical patient-specific preferences (about long-term
      institutionalization and complications from invasive mechanical ventilation) on
      the recommended AD. RESULTS: Our theoretical model recommends endorsing the Full
      Code advance directive for patients who do not have strong preferences against
      having a potential complication from intubation (ETT complications) or being
      discharged to a long-term ECF. However, our model recommends endorsing the DNI
      advance directive for patients who do have strong preferences against having
      potential complications of intubation and are were willing to tradeoff
      substantial amounts of time alive to avoid ETT complications or permanent
      institutionalization. Our theoretical model also recommends endorsing the DNI
      advance directive for patients who have a higher probability of having
      complications from invasive ventilation (ETT). CONCLUSIONS: Our model suggests
      that AD decisions are sensitive to patient preferences about long-term
      institutionalization and potential complications of therapy, particularly in
      patients with severe COPD. Future work will elicit actual patient preferences
      about complications of invasive mechanical ventilation, and incorporate our model
      into a clinical decision support to be used for actual COPD patients facing AD
      decisions.

PMID- 21172023
TI  - An RNAi in silico approach to find an optimal shRNA cocktail against HIV-1.
AB  - BACKGROUND: HIV-1 can be inhibited by RNA interference in vitro through the
      expression of short hairpin RNAs (shRNAs) that target conserved genome sequences.
      In silico shRNA design for HIV has lacked a detailed study of virus variability
      constituting a possible breaking point in a clinical setting. We designed shRNAs
      against HIV-1 considering the variability observed in naive and drug-resistant
      isolates available at public databases. METHODS: A Bioperl-based algorithm was
      developed to automatically scan multiple sequence alignments of HIV, while
      evaluating the possibility of identifying dominant and subdominant viral variants
      that could be used as efficient silencing molecules. Student t-test and
      Bonferroni Dunn correction test were used to assess statistical significance of
      our findings. RESULTS: Our in silico approach identified the most common viral
      variants within highly conserved genome regions, with a calculated free energy of
      >= -6.6 kcal/mol. This is crucial for strand loading to RISC complex and for a
      predicted silencing efficiency score, which could be used in combination for
      achieving over 90% silencing. Resistant and naive isolate variability revealed
      that the most frequent shRNA per region targets a maximum of 85% of viral
      sequences. Adding more divergent sequences maintained this percentage. Specific
      sequence features that have been found to be related with higher silencing
      efficiency were hardly accomplished in conserved regions, even when lower entropy
      values correlated with better scores. We identified a conserved region among most
      HIV-1 genomes, which meets as many sequence features for efficient silencing.
      CONCLUSIONS: HIV-1 variability is an obstacle to achieving absolute silencing
      using shRNAs designed against a consensus sequence, mainly because there are many
      functional viral variants. Our shRNA cocktail could be truly effective at
      silencing dominant and subdominant naive viral variants. Additionally, resistant
      isolates might be targeted under specific antiretroviral selective pressure, but
      in both cases these should be tested exhaustively prior to clinical use.

PMID- 21172024
TI  - Sport, and use of anabolic androgenic steroids among Icelandic high school
      students: a critical test of three perspectives.
AB  - BACKGROUND: This study investigates the use of anabolic androgenic steroids (AAS)
      among a national representative sample of high school students in Iceland. We
      test several hypotheses drawn from three perspectives. The first perspective
      focuses on the use of AAS as an individual phenomenon motivated by the desire to
      succeed in sport. The second perspective views the use of AAS as shaped by norms
      and values embedded in social relationships of formally organized sport. The
      third perspective suggests that factors outside sport, which have been shown to
      correlate with the use of other substances, predict the use of AAS. METHOD: We
      use logistic regression and predicted probabilities to analyze data from a
      national representative survey of 11,031 Icelandic high school students. RESULTS:
      Our results indicated that the use of AAS is not significantly related to
      participation in formally organized sports. However, it positively relates to
      fitness and physical training in informal contexts. We found a relatively strong
      relationship between the use of AAS and the use of illicit substances and a
      moderate relationship between AAS use and alcohol and tobacco consumption. We
      also found a significant negative relationship between AAS use and school
      integration and school achievement, and a significant positive relationship
      between AAS use and school anomie. The relation between AAS use and family
      related variables was weaker. Finally, we found that the relationship between
      sport participation, physical exercise, and AAS use varies across levels of
      anomie and integration. CONCLUSION: Our findings suggest that the use of AAS and
      especially illegal substances should be considered more as a social and a health
      problem rather than a sport specific issue. We found that high school students
      participating in fitness and informal training outside of formally organized
      sport clubs are the main risk group and should be the target of prevention
      efforts. However, this should not be done at the expense of general risk factors
      that affect AAS and other substances used by the general population. Finally, we
      suggest that prevention efforts should target both groups and individuals.

PMID- 21172025
TI  - Downregulation of miR-342 is associated with tamoxifen resistant breast tumors.
AB  - BACKGROUND: Tumor resistance to the selective estrogen receptor modulator
      tamoxifen remains a serious clinical problem especially in patients with tumors
      that also overexpress HER2. We have recently demonstrated that the clinically
      important isoform of HER2, HERDelta16, promotes therapeutically refractory breast
      cancer including resistance to endocrine therapy. Likewise additional breast
      tumor cell models of tamoxifen resistance have been developed that do not involve
      HER2 overexpression. However, a unifying molecular mechanism of tamoxifen
      resistance has remained elusive. RESULTS: Here we analyzed multiple cell models
      of tamoxifen resistance derived from MCF-7 cells to examine the influence of
      microRNAs (miRNAs) on tamoxifen resistance. We compared miRNA expression profiles
      of tamoxifen sensitive MCF-7 cells and tamoxifen resistant MCF-7/HER2Delta16
      cells. We observed significant and dramatic downregulation of miR-342 in the MCF
      7/HER2Delta16 cell line as well as the HER2 negative but tamoxifen resistant MCF
      7 variants TAMR1 and LCC2. Restoring miR-342 expression in the MCF-7/HER2Delta16
      and TAMR1 cell lines sensitized these cells to tamoxifen-induced apoptosis with a
      dramatic reduction in cell growth. Expression of miR-342 was also reduced in a
      panel of tamoxifen refractory human breast tumors, underscoring the potential
      clinical importance of miR-342 downregulation. Towards the goal of identifying
      direct and indirect targets of miR-342 we restored miR-342 expression in MCF
      7/HER2Delta16 cells and analyzed changes in global gene expression by microarray.
      The impact of miR-342 on gene expression in MCF-7/HER2Delta16 cells was not
      limited to miR-342 in silica predicted targets. Ingenuity Pathways Analysis of
      the dataset revealed a significant influence of miR-342 on multiple tumor cell
      cycle regulators. CONCLUSIONS: Our findings suggest that miR-342 regulates
      tamoxifen response in breast tumor cell lines and our clinical data indicates a
      trend towards reduced miR-342 expression and tamoxifen resistance. In addition,
      our results suggest that miR-342 regulates expression of genes involved in
      tamoxifen mediated tumor cell apoptosis and cell cycle progression. Restoring miR
      342 expression may represent a novel therapeutic approach to sensitizing and
      suppressing the growth of tamoxifen refractory breast tumors.

PMID- 21172026
TI  - Contingency management to reduce methamphetamine use and sexual risk among men
      who have sex with men: a randomized controlled trial.
AB  - BACKGROUND: Methamphetamine use is associated with HIV acquisition and
      transmission among men who have sex with men (MSM). Contingency management (CM),
      providing positive reinforcement for drug abstinence and withholding
      reinforcement when abstinence is not demonstrated, may facilitate reduced
      methamphetamine use and sexual risk. We compared CM as a stand-alone intervention
      to a minimal intervention control to assess the feasibility of conducting a
      larger, more definitive trial of CM; to define the frequency of behavioral
      outcomes to power such a trial; and, to compute preliminary estimates of CM's
      effectiveness. METHODS: We randomly assigned 127 MSM from Seattle, WA who use
      methamphetamine to receive a 12-week CM intervention (n = 70) or referral to
      community resources (n = 57). RESULTS: Retention at 24 weeks was 84%. Comparing
      consecutive study visits, non-concordant UAI declined significantly in both study
      arms. During the intervention, CM and control participants were comparably likely
      to provide urine samples containing methamphetamine (adjusted relative risk [aRR]
      = 1.09; 95%CI: 0.71, 1.56) and to report non-concordant UAI (aRR = 0.80; 95%CI:
      0.47, 1.35). However, during post-intervention follow-up, CM participants were
      somewhat more likely to provide urine samples containing methamphetamine than
      control participants (aRR = 1.21; 95%CI: 0.95, 1.54, P = 0.11). Compared to
      control participants, CM participants were significantly more likely to report
      weekly or more frequent methamphetamine use and use of more than eight quarters
      of methamphetamine during the intervention and post-intervention periods.
      CONCLUSIONS: While it is possible to enroll and retain MSM who use
      methamphetamine in a trial of CM conducted outside drug treatment, our data
      suggest that CM is not likely to have a large, sustained effect on
      methamphetamine use.

PMID- 21172027
TI  - DNA damage and cell cycle events implicate cerebellar dentate nucleus neurons as
      targets of Alzheimer's disease.
AB  - BACKGROUND: Although the cerebellum is considered to be predominantly involved in
      fine motor control, emerging evidence documents its participation in language,
      impulsive behavior and higher cognitive functions. While the specific connections
      of the cerebellar deep nuclei (CDN) that are responsible for these functions are
      still being worked out, their deficiency has been termed "cerebellar cognitive
      affective syndrome" - a syndrome that bears a striking similarity to many of the
      symptoms of Alzheimer's disease (AD). Using ectopic cell cycle events and DNA
      damage markers as indexes of cellular distress, we have explored the
      neuropathological involvement of the CDN in human AD. RESULTS: We examined the
      human cerebellar dentate nucleus in 22 AD cases and 19 controls for the presence
      of neuronal cell cycle events and DNA damage using immunohistochemistry and
      fluorescence in situ hybridization. Both techniques revealed several instances of
      highly significant correlations. By contrast, neither amyloid plaque nor
      neurofibrillary tangle pathology was detected in this region, consistent with
      previous reports of human cerebellar pathology. Five cases of early stage AD were
      examined and while cell cycle and DNA damage markers were well advanced in the
      hippocampus of all five, few indicators of either cell cycle events (1 case) or a
      DNA damage response (1 case) were found in CDN. This implies that CDN neurons are
      most likely affected later in the course of AD. Clinical-pathological
      correlations revealed that cases with moderate to high levels of cell cycle
      activity in their CDN are highly likely to show deficits in unorthodox cerebellar
      functions including speech, language and motor planning. CONCLUSION: Our results
      reveal that the CDN neurons are under cellular stress in AD and suggest that some
      of the non-motor symptoms found in patients with AD may be partly cerebellar in
      origin.

PMID- 21172028
TI  - Hashimoto thyroiditis is more frequent than expected when diagnosed by cytology
      which uncovers a pre-clinical state.
AB  - BACKGROUND: Our Thyroid-Multidisciplinary Clinic is a large referral site for
      thyroid diseases. Thyroid biopsies are mainly performed for thyroid cancer
      screening. Yet, Hashimoto thyroiditis (HT) is being too frequently diagnosed. The
      prevalence of HT is reported as 0.3-1.2% or twice the prevalence of type 1
      diabetes. However, the prevalence of HT confirmed by cytology is still uncertain.
      To evaluate different aspects of thyroid physiopathology including prevalence of
      Hashimoto's, a database of clinical features, ultrasound images and cytology
      results of patients referred for FNA of thyroid nodules was prospectively
      developed. METHODS: We retrospectively studied 811 consecutive patients for whom
      ultrasound guided thyroid FNA biopsies were performed at our clinic over 2.5 year
      period (Mar/2006-Sep/2008). RESULTS: The analysis of our database revealed that
      from 761 patients, 102 (13.4%) had HT, from whom 56 (7.4%) were euthyroid or had
      sub-clinical (non-hypothyroid) disease, and 46 (6%) were clinically hypothyroid.
      CONCLUSIONS: This is the first study to show such a high prevalence of HT
      diagnosed by ultrasound-guided FNA. More strikingly, the prevalence of euthyroid
      HT, appears to be >5% similar to that of type 2 diabetes. Based on our results,
      there might be a need to follow up on cytological Hashimoto's to monitor for
      thyroid failure, especially in high risk states, like pregnancy. The potential
      risk for thyroid cancer in patients with biopsy-proven inflammation of thyroid
      epithelium remains to be established prospectively. However, it may explain the
      increased risk for thyroid cancer observed in patients with elevated but within
      normal TSH.

PMID- 21172029
TI  - Introduction of customized inserts for s-treamlined assembly and optimization of
      BioBrick synthetic genetic circuits.
AB  - BACKGROUND: BioBrick standard biological parts are designed to make biological
      systems easier to engineer (e.g. assemble, manipulate, and modify). There are
      over 5,000 parts available in the Registry of Standard Biological Parts that can
      be easily assembled into genetic circuits using a standard assembly technique.
      The standardization of the assembly technique has allowed for wide distribution
      to a large number of users -- the parts are reusable and interchangeable during
      the assembly process. The standard assembly process, however, has some
      limitations. In particular it does not allow for modification of already
      assembled biological circuits, addition of protein tags to pre-existing BioBrick
      parts, or addition of non-BioBrick parts to assemblies. RESULTS: In this paper we
      describe a simple technique for rapid generation of synthetic biological circuits
      using introduction of customized inserts. We demonstrate its use in Escherichia
      coli (E. coli) to express green fluorescent protein (GFP) at pre-calculated
      relative levels and to add an N-terminal tag to GFP. The technique uses a new
      BioBrick part (called a BioScaffold) that can be inserted into cloning vectors
      and excised from them to leave a gap into which other DNA elements can be placed.
      The removal of the BioScaffold is performed by a Type IIB restriction enzyme
      (REase) that recognizes the BioScaffold but cuts into the surrounding sequences;
      therefore, the placement and removal of the BioScaffold allows the creation of
      seamless connections between arbitrary DNA sequences in cloning vectors. The
      BioScaffold contains a built-in red fluorescent protein (RFP) reporter;
      successful insertion of the BioScaffold is, thus, accompanied by gain of red
      fluorescence and its removal is manifested by disappearance of the red
      fluorescence. CONCLUSIONS: The ability to perform targeted modifications of
      existing BioBrick circuits with BioScaffolds (1) simplifies and speeds up the
      iterative design-build-test process through direct reuse of existing circuits,
      (2) allows incorporation of sequences incompatible with BioBrick assembly into
      BioBrick circuits (3) removes scar sequences between standard biological parts,
      and (4) provides a route to adapt synthetic biology innovations to BioBrick
      assembly through the creation of new parts rather than new assembly standards or
      parts collections.

PMID- 21172030
TI  - Treatment of dyslipidemia in patients with type 2 diabetes.
AB  - Type 2 diabetes is associated with significant cardiovascular morbidity and
      mortality. Although low-density lipoprotein cholesterol levels may be normal in
      patients with type 2 diabetes, insulin resistance drives a number of changes in
      lipid metabolism and lipoprotein composition that render low-density lipoprotein
      cholesterol and other lipoproteins more pathogenic than species found in patients
      without type 2 diabetes. Dyslipidemia, which affects almost 50% of patients with
      type 2 diabetes, is a cardiovascular risk factor characterized by elevated
      triglyceride levels, low high-density lipoprotein cholesterol levels, and a
      preponderance of small, dense, low-density lipoprotein particles. Early,
      aggressive pharmacological management is advocated to reduce low-density
      lipoprotein cholesterol levels, regardless of baseline levels. A number of lipid
      lowering agents, including statins, fibrates, niacin, and bile acid sequestrants,
      are available to target normalization of the entire lipid profile. Despite use of
      combination and high-dose lipid-lowering agents, many patients with type 2
      diabetes do not achieve lipid targets. This review outlines the characteristics
      and prevalence of dyslipidemia in patients with type 2 diabetes and discusses
      strategies that may reduce the risk of cardiovascular disease in this population.

PMID- 21172032
TI  - Whole-exome sequencing for finding de novo mutations in sporadic mental
      retardation.
AB  - Recent work has used a family-based approach and whole-exome sequencing to
      identify de novo mutations in sporadic cases of mental retardation.

PMID- 21172031
TI  - beta-Adrenoceptor activation depresses brain inflammation and is neuroprotective
      in lipopolysaccharide-induced sensitization to oxygen-glucose deprivation in
      organotypic hippocampal slices.
AB  - BACKGROUND: Inflammation acting in synergy with brain ischemia aggravates
      perinatal ischemic brain damage. The sensitizing effect of pro-inflammatory
      exposure prior to hypoxia is dependent on signaling by TNF-alpha through TNF
      receptor (TNFR) 1. Adrenoceptor (AR) activation is known to modulate the immune
      response and synaptic transmission. The possible protective effect of alpha and
      beta AR activation against neuronal damage caused by tissue ischemia and
      inflammation, acting in concert, was evaluated in murine hippocampal organotypic
      slices treated with lipopolysaccharide (LPS) and subsequently subjected to oxygen
      glucose deprivation (OGD). METHOD: Hippocampal slices from mice were obtained at
      P6, and were grown in vitro for 9 days on nitrocellulose membranes. Slices were
      treated with beta1(dobutamine)-, beta2(terbutaline)-, alpha1(phenylephrine)- and
      alpha2(clonidine)-AR agonists (5 and 50 MUM, respectively) during LPS (1 MUg/mL,
      24 h) -exposure followed by exposure to OGD (15 min) in a hypoxic chamber. Cell
      death in the slice CA1 region was assessed by propidium iodide staining of dead
      cells. RESULTS: Exposure to LPS + OGD caused extensive cell death from 4 up to 48
      h after reoxygenation. Co-incubation with beta1-agonist (50 MUM) during LPS
      exposure before OGD conferred complete protection from cell death (P < 0.001)
      whereas the beta2-agonist (50 MUM) was partially protective (p < 0.01).
      Phenylephrine was weakly protective while no protection was attained by
      clonidine. Exposure to both beta1- and beta2-agonist during LPS exposure
      decreased the levels of secreted TNF-alpha, IL-6 and monocyte chemoattractant
      protein-1 and prevented microglia activation in the slices. Dobutamine remained
      neuroprotective in slices exposed to pure OGD as well as in TNFR1-/- and TNFR2-/-
      slices exposed to LPS followed by OGD. CONCLUSIONS: Our data demonstrate that
      activation of both beta1- and beta2-receptors is neuroprotective and may offer
      mechanistic insights valuable for development of neuro-protective strategies in
      neonates.

PMID- 21172033
TI  - The impact of a 6-year comprehensive community trial on the awareness, treatment
      and control rates of hypertension in Iran: experiences from the Isfahan healthy
      heart program.
AB  - OBJECTIVES: We aimed to evaluate the changes over time in the prevalence,
      awareness, treatment, and control rate of hypertension in intervention and
      reference areas of a comprehensive community trial with reference area. METHODS:
      Data from independent sample surveys before and after implementation of the
      program (2001 vs.2007) were used to compare differences in the intervention and
      references areas over time. Hypertension was defined as blood pressure >=140/90
      mmHg in non-diabetic patients and >=130/80 mmHg in diabetic individuals and or
      taking antihypertensive medications. Interventional activities included
      educational strategies at population level as well as for hypertensive patients,
      their families and health professionals. RESULTS: The study population of the
      baseline survey included 6175 (48.7% males) in the interventional area and 6339
      (51.3% male) in the reference area. The corresponding figures in the post
      intervention phase was 4717 (49.3% male) in the interventional area and 4853
      (50.7% male) individuals in the reference area. The prevalence of hypertension
      had a non-significant decrease from 20.5%to 19.6%, in the interventional area
      whereas in the reference area, it increased from 17.4% to 19.6% (P = 0.003). If
      we consider Bp >= 140/90 in diabetic and non-diabetic patients as hypertension
      definition, the prevalence of hypertension in the interventional areas had a non
      significant decrease from 18.9% in 2001 to 17.8% in 2007, whereas in the
      reference area, it had a significant rise from 15.7% to 17.9% (P = 0.002)
      respectively. Awareness, treatment and control rates of hypertension had better
      improvement in urban and rural part of the interventional area compared to
      reference area. The awareness, treatment, and control rates of hypertension
      increased significantly in the age groups of more than 40 years, as well as in
      all groups of body mass index in interventional areas without significant change
      in the reference area. Mean systolic blood pressure of study population in the
      interventional area decreased from 116.13 +/-19.37 to 112.92 +/- 18.27 mmHg (P <
      0.001) without significant change in reference area. CONCLUSIONS: This
      comprehensive and integrated program of interventions was effective in tackling
      with the prevalence of hypertension, and may improve the awareness, treatment and
      control rates of this disorder in a developing country setting.

PMID- 21172034
TI  - Content-based microarray search using differential expression profiles.
AB  - BACKGROUND: With the expansion of public repositories such as the Gene Expression
      Omnibus (GEO), we are rapidly cataloging cellular transcriptional responses to
      diverse experimental conditions. Methods that query these repositories based on
      gene expression content, rather than textual annotations, may enable more
      effective experiment retrieval as well as the discovery of novel associations
      between drugs, diseases, and other perturbations. RESULTS: We develop methods to
      retrieve gene expression experiments that differentially express the same
      transcriptional programs as a query experiment. Avoiding thresholds, we generate
      differential expression profiles that include a score for each gene measured in
      an experiment. We use existing and novel dimension reduction and correlation
      measures to rank relevant experiments in an entirely data-driven manner, allowing
      emergent features of the data to drive the results. A combination of matrix
      decomposition and p-weighted Pearson correlation proves the most suitable for
      comparing differential expression profiles. We apply this method to index all GEO
      DataSets, and demonstrate the utility of our approach by identifying pathways and
      conditions relevant to transcription factors Nanog and FoxO3. CONCLUSIONS:
      Content-based gene expression search generates relevant hypotheses for biological
      inquiry. Experiments across platforms, tissue types, and protocols inform the
      analysis of new datasets.

PMID- 21172035
TI  - Association between HLA-DRB1 alleles polymorphism and hepatocellular carcinoma: a
      meta-analysis.
AB  - BACKGROUND: HLA-DRB1 allele polymorphisms have been reported to be associated
      with hepatocellular carcinoma susceptibility, but the results of these previous
      studies have been inconsistent. The purpose of the present study was to explore
      whether specific HLA-DRB1 alleles (DRB1*07, DRB1*12, DRB1*15) confer
      susceptibility to hepatocellular carcinoma. METHODS: Case-control studies on HLA
      DRB1 alleles association with HCC were searched up to January 2010 through a
      systematic review of the literature. The odds ratios (ORs) of HLA-DRB1 allele
      distributions in patients with hepatocellular carcinoma were analyzed against
      healthy controls. The meta-analysis software REVMAN 5.0 was applied for
      investigating heterogeneity among individual studies and for summarizing all the
      studies. Meta-analysis was performed using fixed-effect or random-effect methods,
      depending on absence or presence of significant heterogeneity. RESULTS: Eight
      case-control studies were included in the final analysis. Among the 3 HLA-DRB1
      alleles studied, DRB1*07 and DRB1*12 were significantly associated with the risk
      of HCC in the whole populations (OR = 1.65, 95% CI: 1.08-2.51, P = 0.02 and OR =
      1.59, 95% CI: 1.09-2.32, P = 0.02, respectively). No significant association was
      established for DRB1*15 allele with HCC in the whole populations. Subgroup
      analysis by ethnicity showed that DRB1*07, DRB1*12 and DRB1*15 alleles
      significantly increased the risk of hepatocellular carcinoma in Asians (OR =
      2.10, 95% CI: 1.06-4.14, P = 0.03; OR = 1.73, 95% CI: 1.17-2.57, P = 0.006 and OR
      = 2.88, 95%CI: 1.77-4.69, P <0.001, respectively). CONCLUSION: These results
      support the hypothesis that specific HLA-DRB1 alleles might influence the
      susceptibility of hepatocellular carcinoma. Large, multi-ethnic confirmatory and
      well designed studies are needed to determine the host genetic determinants of
      hepatocellular carcinoma.

PMID- 21172036
TI  - Computing DNA duplex instability profiles efficiently with a two-state model:
      trends of promoters and binding sites.
AB  - BACKGROUND: DNA instability profiles have been used recently for predicting the
      transcriptional start site and the location of core promoters, and to gain
      insight into promoter action. It was also shown that the use of these profiles
      can significantly improve the performance of motif finding programs. RESULTS: In
      this work we introduce a new method for computing DNA instability profiles. The
      model that we use is a modified Ising-type model and it is implemented via
      statistical mechanics. Our linear time algorithm computes the profile of a 10,000
      base-pair long sequence in less than one second. The method we use also allows
      the computation of the probability that several consecutive bases are unpaired
      simultaneously. This is a feature that is not available in other linear-time
      algorithms. We use the model to compare the thermodynamic trends of promoter
      sequences of several genomes. In addition, we report results that associate the
      location of local extrema in the instability profiles with the presence of core
      promoter elements at these locations and with the location of the transcription
      start sites (TSS). We also analyzed the instability scores of binding sites of
      several human core promoter elements. We show that the instability scores of
      functional binding sites of a given core promoter element are significantly
      different than the scores of sites with the same motif occurring outside the
      functional range (relative to the TSS). CONCLUSIONS: The time efficiency of the
      algorithm and its genome-wide applications makes this work of broad interest to
      scientists interested in transcriptional regulation, motif discovery, and
      comparative genomics.

PMID- 21172038
TI  - Epigenome targeting by probiotic metabolites.
AB  - BACKGROUND: The intestinal microbiota plays an important role in immune
      development and homeostasis. A disturbed microbiota during early infancy is
      associated with an increased risk of developing inflammatory and allergic
      diseases later in life. The mechanisms underlying these effects are poorly
      understood but are likely to involve alterations in microbial production of
      fermentation-derived metabolites, which have potent immune modulating properties
      and are required for maintenance of healthy mucosal immune responses. Probiotics
      are beneficial bacteria that have the capacity to alter the composition of
      bacterial species in the intestine that can in turn influence the production of
      fermentation-derived metabolites. Principal among these metabolites are the short
      chain fatty acids butyrate and acetate that have potent anti-inflammatory
      activities important in regulating immune function at the intestinal mucosal
      surface. Therefore strategies aimed at restoring the microbiota profile may be
      effective in the prevention or treatment of allergic and inflammatory diseases.
      PRESENTATION OF THE HYPOTHESIS: Probiotic bacteria have diverse effects including
      altering microbiota composition, regulating epithelial cell barrier function and
      modulating of immune responses. The precise molecular mechanisms mediating these
      probiotic effects are not well understood. Short-chain fatty acids such as
      butyrate are a class of histone deacetylase inhibitors important in the
      epigenetic control of host cell responses. It is hypothesized that the biological
      function of probiotics may be a result of epigenetic modifications that may
      explain the wide range of effects observed. Studies delineating the effects of
      probiotics on short-chain fatty acid production and the epigenetic actions of
      short-chain fatty acids will assist in understanding the association between
      microbiota and allergic or autoimmune disorders. TESTING THE HYPOTHESIS: We
      propose that treatment with specific probiotic bacteria under in vivo conditions
      would offer the ideal conditions to examine the microbiological, immunological
      and epigenetic mechanisms of action. Advances in epigenetic technology now allow
      investigators to better understand the complex biological properties of
      probiotics and their metabolites. IMPLICATIONS OF THE HYPOTHESIS: Determining the
      precise mechanisms of probiotic action will lead to more specific and efficacious
      therapeutic strategies in the prevention or treatment of chronic inflammatory
      conditions.

PMID- 21172037
TI  - Analgesic effect of highly reversible omega-conotoxin FVIA on N type Ca2+
      channels.
AB  - BACKGROUND: N-type Ca2+ channels (Ca(v)2.2) play an important role in the
      transmission of pain signals to the central nervous system. omega-Conotoxin (CTx)
      MVIIA, also called ziconotide (Prialt(r)), effectively alleviates pain, without
      causing addiction, by blocking the pores of these channels. Unfortunately, CTx
      MVIIA has a narrow therapeutic window and produces serious side effects due to
      the poor reversibility of its binding to the channel. It would thus be desirable
      to identify new analgesic blockers with binding characteristics that lead to
      fewer adverse side effects. RESULTS: Here we identify a new CTx, FVIA, from the
      Korean Conus Fulmen and describe its effects on pain responses and blood
      pressure. The inhibitory effect of CTx-FVIA on N-type Ca2+ channel currents was
      dose-dependent and similar to that of CTx-MVIIA. However, the two conopeptides
      exhibited markedly different degrees of reversibility after block. CTx-FVIA
      effectively and dose-dependently reduced nociceptive behavior in the formalin
      test and in neuropathic pain models, and reduced mechanical and thermal allodynia
      in the tail nerve injury rat model. CTx-FVIA (10 ng) also showed significant
      analgesic effects on writhing in mouse neurotransmitter- and cytokine-induced
      pain models, though it had no effect on acute thermal pain and interferon-gamma
      induced pain. Interestingly, although both CTx-FVIA and CTx-MVIIA depressed
      arterial blood pressure immediately after administration, pressure recovered
      faster and to a greater degree after CTx-FVIA administration. CONCLUSIONS: The
      analgesic potency of CTx-FVIA and its greater reversibility could represent
      advantages over CTx-MVIIA for the treatment of refractory pain and contribute to
      the design of an analgesic with high potency and low side effects.

PMID- 21172041
TI  - Immunodiagnosis of Tuberculosis: New Questions, New Tools Virginia, VA, USA. 21
      23 September 2008. Abstracts.

PMID- 21172039
TI  - Endotoxin and CD14 in the progression of biliary atresia.
AB  - BACKGROUND: Biliary atresia (BA) is a typical cholestatic neonatal disease,
      characterized by obliteration of intra- and/or extra-hepatic bile ducts. However,
      the mechanisms contributing to the pathogenesis of BA remain uncertain. Because
      of decreased bile flow, infectious complications and damaging endotoxemia occur
      frequently in patients with BA. The aim of this study was to investigate
      endotoxin levels in patients with BA and the relation of these levels with the
      expression of the endotoxin receptor, CD14. METHODS: The plasma levels of
      endotoxin and soluble CD14 were measured with a pyrochrome Limulus amebocyte
      lysate assay and enzyme-linked immunosorbent assay in patients with early-stage
      BA when they received the Kasai procedure (KP), in patients who were jaundice
      free post-KP and followed-up at the outpatient department, in patients with late
      stage BA when they received liver transplantation, and in patients with
      choledochal cysts. The correlation of CD14 expression with endotoxin levels in
      rats following common bile duct ligation was investigated. RESULTS: The results
      demonstrated a significantly higher hepatic CD14 mRNA and soluble CD14 plasma
      levels in patients with early-stage BA relative to those with late-stage BA.
      However, plasma endotoxin levels were significantly higher in both the early and
      late stages of BA relative to controls. In rat model, the results demonstrated
      that both endotoxin and CD14 levels were significantly increased in liver tissues
      of rats following bile duct ligation. CONCLUSIONS: The significant increase in
      plasma endotoxin and soluble CD14 levels during BA implies a possible involvement
      of endotoxin stimulated CD14 production by hepatocytes in the early stage of BA
      for removal of endotoxin; whereas, endotoxin signaling likely induced liver
      injury and impaired soluble CD14 synthesis in the late stages of BA.

PMID- 21172040
TI  - Characteristics associated with organic food consumption during pregnancy; data
      from a large cohort of pregnant women in Norway.
AB  - BACKGROUND: Little is known about the use of organic food during pregnancy. The
      aim of this study was to describe characteristics associated with the use of
      organic food among pregnant women participating in the Norwegian Mother and Child
      Cohort Study (MoBa). METHODS: The present study includes 63,561 women who during
      the years 2002-2007 answered two questionnaires, a general health questionnaire
      at gestational week 15 and a food frequency questionnaire at weeks 17-22. We used
      linear binomial regression with frequent versus rare use of organic food as
      outcome variable and characteristics of the respondent as independent variables.
      The outcome variable was derived from self-reported frequency of organic food use
      in six main food groups (milk/dairy, bread/cereal, eggs, vegetables, fruit and
      meat). RESULTS: Organic eggs and vegetables were the food items which were most
      frequently reported to be used "often" or "mostly". The proportion of women
      reporting frequent intake of organic food was 9.1% (n = 5754). This group
      included more women in the lower (<25 years) and higher (>40 years) age-groups,
      with normal or low body mass index, who were vegetarians, exercised regularly
      (3+times weekly), consumed alcohol and smoked cigarettes during pregnancy (p <
      0.001 for all, except alcohol: p=0.044). Further, participants with frequent
      organic consumption included more women in the lower (<= 12 years) or higher (17
      years +) category of educational attainment, women who were students or had a
      partner being a student, who belonged to the lowest household income group (both
      respondent and her partner earned <300,000 NOK), who entered the study 2005-2007,
      and who lived in an urban area (p < 0.001 for all). CONCLUSIONS: The socio
      economic characteristics of pregnant Norwegian women with frequent organic
      consumption did not unambiguously follow those typically associated with better
      health, such as higher levels of education and income. Rather, lower household
      income, and both lowest and highest levels of education were associated with a
      higher prevalence of frequent organic consumption. The results indicate that
      personal and socio-economic characteristics are important covariates and need to
      be included in future studies of potential health outcomes related to organic
      food consumption during pregnancy.

PMID- 21172042
TI  - Creating a blood line from human skin.
AB  - A recent study has generated blood cell progenitors with therapeutic potential by
      direct lineage conversion of human fibroblasts, thus circumventing reprogramming
      to pluripotent stem cells.

PMID- 21172044
TI  - Association of tissue lineage and gene expression: conservatively and
      differentially expressed genes define common and special functions of tissues.
AB  - BACKGROUND: Embryogenesis is the process by which the embryo is formed, develops,
      and establishes developmental hierarchies of tissues. The recent advance in
      microarray technology made it possible to investigate the tissue specific
      patterns of gene expression and their relationship with tissue lineages. This
      study is focused on how tissue specific functions, tissue lineage, and cell
      differentiation are correlated, which is essential to understand embryonic
      development and organism complexity. RESULTS: We performed individual gene and
      gene set based analysis on multiple tissue expression data, in association with
      the classic topology of mammalian fate maps of embryogenesis. For each sub-group
      of tissues on the fate map, conservatively, differentially and correlatively
      expressed genes or gene sets were identified. Tissue distance was found to
      correlate with gene expression divergence. Tissues of the ectoderm or mesoderm
      origins from the same segments on the fate map shared more similar expression
      pattern than those from different origins. Conservatively expressed genes or gene
      sets define common functions in a tissue group and are related to tissue specific
      diseases, which is supported by results from Gene Ontology and KEGG pathway
      analysis. Gene expression divergence is larger in certain human tissues than in
      the mouse homologous tissues. CONCLUSION: The results from tissue lineage and
      gene expression analysis indicate that common function features of neighbor
      tissue groups were defined by the conservatively expressed genes and were related
      to tissue specific diseases, and differentially expressed genes contribute to the
      functional divergence of tissues. The difference of gene expression divergence in
      human and mouse homologous tissues reflected the organism complexity, i.e.
      distinct neural development levels and different body sizes.

PMID- 21172045
TI  - Accurate HLA type inference using a weighted similarity graph.
AB  - BACKGROUND: The human leukocyte antigen system (HLA) contains many highly
      variable genes. HLA genes play an important role in the human immune system, and
      HLA gene matching is crucial for the success of human organ transplantations.
      Numerous studies have demonstrated that variation in HLA genes is associated with
      many autoimmune, inflammatory and infectious diseases. However, typing HLA genes
      by serology or PCR is time consuming and expensive, which limits large-scale
      studies involving HLA genes. Since it is much easier and cheaper to obtain single
      nucleotide polymorphism (SNP) genotype data, accurate computational algorithms to
      infer HLA gene types from SNP genotype data are in need. To infer HLA types from
      SNP genotypes, the first step is to infer SNP haplotypes from genotypes. However,
      for the same SNP genotype data set, the haplotype configurations inferred by
      different methods are usually inconsistent, and it is often difficult to decide
      which one is true. RESULTS: In this paper, we design an accurate HLA gene type
      inference algorithm by utilizing SNP genotype data from pedigrees, known HLA gene
      types of some individuals and the relationship between inferred SNP haplotypes
      and HLA gene types. Given a set of haplotypes inferred from the genotypes of a
      population consisting of many pedigrees, the algorithm first constructs a
      weighted similarity graph based on a new haplotype similarity measure and derives
      constraint edges from known HLA gene types. Based on the principle that different
      HLA gene alleles should have different background haplotypes, the algorithm
      searches for an optimal labeling of all the haplotypes with unknown HLA gene
      types such that the total weight among the same HLA gene types is maximized. To
      deal with ambiguous haplotype solutions, we use a genetic algorithm to select
      haplotype configurations that tend to maximize the same optimization criterion.
      Our experiments on a previously typed subset of the HapMap data show that the
      algorithm is highly accurate, achieving an accuracy of 96% for gene HLA-A, 95%
      for HLA-B, 97% for HLA-C, 84% for HLA-DRB1, 98% for HLA-DQA1 and 97% for HLA-DQB1
      in a leave-one-out test. CONCLUSIONS: Our algorithm can infer HLA gene types from
      neighboring SNP genotype data accurately. Compared with a recent approach on the
      same input data, our algorithm achieved a higher accuracy. The code of our
      algorithm is available to the public for free upon request to the corresponding
      authors.

PMID- 21172046
TI  - MiRenSVM: towards better prediction of microRNA precursors using an ensemble SVM
      classifier with multi-loop features.
AB  - BACKGROUND: MicroRNAs (simply miRNAs) are derived from larger hairpin RNA
      precursors and play essential regular roles in both animals and plants. A number
      of computational methods for miRNA genes finding have been proposed in the past
      decade, yet the problem is far from being tackled, especially when considering
      the imbalance issue of known miRNAs and unidentified miRNAs, and the pre-miRNAs
      with multi-loops or higher minimum free energy (MFE). This paper presents a new
      computational approach, miRenSVM, for finding miRNA genes. Aiming at better
      prediction performance, an ensemble support vector machine (SVM) classifier is
      established to deal with the imbalance issue, and multi-loop features are
      included for identifying those pre-miRNAs with multi-loops. RESULTS: We collected
      a representative dataset, which contains 697 real miRNA precursors identified by
      experimental procedure and other computational methods, and 5428 pseudo ones from
      several datasets. Experiments showed that our miRenSVM achieved a 96.5%
      specificity and a 93.05% sensitivity on the dataset. Compared with the state-of
      the-art approaches, miRenSVM obtained better prediction results. We also applied
      our method to predict 14 Homo sapiens pre-miRNAs and 13 Anopheles gambiae pre
      miRNAs that first appeared in miRBase13.0, MiRenSVM got a 100% prediction rate.
      Furthermore, performance evaluation was conducted over 27 additional species in
      miRBase13.0, and 92.84% (4863/5238) animal pre-miRNAs were correctly identified
      by miRenSVM. CONCLUSION: MiRenSVM is an ensemble support vector machine (SVM)
      classification system for better detecting miRNA genes, especially those with
      multi-loop secondary structure.

PMID- 21172047
TI  - Detection and reconstruction of tandemly organized de novo copy number
      variations.
AB  - BACKGROUND: The characterization of structural variations (SV) such as
      insertions, deletions and copy number variations is a critical step in the
      process of understanding the full genetic architecture of organisms. Copy number
      variations (CNV) have attracted much recent attention due to their effects on
      gene expression and disease status. RESULTS: In this paper, we present a method
      that utilizes next-generation sequencing technologies (NGS), in order to both
      detect and reconstruct CNVs. We focus on a special type of CNV, namely tandemly
      organized de novo CNVs, which have been shown to occur with high frequency in the
      mouse genome. CONCLUSIONS: We apply our method to CNV regions randomly inserted
      into the reference mouse genome and show that our method achieves good
      performance for both detection and reconstruction of tandemly organized de novo
      CNVs.

PMID- 21172048
TI  - Revealing parasite influence in metabolic pathways in Apicomplexa infected
      patients.
AB  - BACKGROUND: As an obligate intracellular parasite, Apicomplexa interacts with the
      host in the special living environment, competing for energy and nutrients from
      the host cells by manipulating the host metabolism. Previous studies of host
      parasite interaction mainly focused on using cellular and biochemical methods to
      investigate molecular functions in metabolic pathways of parasite infected hosts.
      Computational approaches taking advantage of high-throughput biological data and
      topology of metabolic pathways have a great potential in revealing the details
      and mechanism of parasites-to-host interactions. A new analytical method was
      designed in this work to study host-parasite interactions in human cells infected
      with Plasmodium falciparum and Cryptosporidium parvum. RESULTS: We introduced a
      new method that analyzes the host metabolic pathways in divided parts: host
      specific subpathways and host-parasite common subpathways. Upon analysis on gene
      expression data from cells infected by Plasmodium falciparum or Cryptosporidium
      parvum, we found: (i) six host-parasite common subpathways and four host specific
      subpathways were significantly altered in plasmodium infected human cells; (ii)
      plasmodium utilized fatty acid biosynthesis and elongation, and Pantothenate and
      CoA biosynthesis to obtain nutrients from host environment; (iii) in
      Cryptosporidium parvum infected cells, most of the host-parasite common enzymes
      were down-regulated, whereas the host specific enzymes up-regulated; (iv) the
      down-regulation of common subpathways in host cells might be caused by
      competition for the substrates and up-regulation of host specific subpathways may
      be stimulated by parasite infection. CONCLUSION: Results demonstrated a
      significantly coordinated expression pattern between the two groups of
      subpathways. The method helped expose the impact of parasite infection on host
      cell metabolism, which was previously concealed in the pathway enrichment
      analysis. Our approach revealed detailed subpathways and metabolic information
      are important to the symbiosis in two kinds of the apicomplex parasites, and
      highlighted its significance in research and understanding of parasite-host
      interactions.

PMID- 21172049
TI  - The utility of mass spectrometry-based proteomic data for validation of novel
      alternative splice forms reconstructed from RNA-Seq data: a preliminary
      assessment.
AB  - BACKGROUND: Most mass spectrometry (MS) based proteomic studies depend on
      searching acquired tandem mass (MS/MS) spectra against databases of known protein
      sequences. In these experiments, however, a large number of high quality spectra
      remain unassigned. These spectra may correspond to novel peptides not present in
      the database, especially those corresponding to novel alternative splice (AS)
      forms. Recently, fast and comprehensive profiling of mammalian genomes using deep
      sequencing (i.e. RNA-Seq) has become possible. MS-based proteomics can
      potentially be used as an aid for protein-level validation of novel AS events
      observed in RNA-Seq data. RESULTS: In this work, we have used publicly available
      mouse tissue proteomic and RNA-Seq datasets and have examined the feasibility of
      using MS data for the identification of novel AS forms by searching MS/MS spectra
      against translated mRNA sequences derived from RNA-Seq data. A significant
      correlation between the likelihood of identifying a peptide from MS/MS data and
      the number of reads in RNA-Seq data for the same gene was observed. Based on in
      silico experiments, it was also observed that only a fraction of novel AS forms
      identified from RNA-Seq had the corresponding junction peptide compatible with
      MS/MS sequencing. The number of novel peptides that were actually identified from
      MS/MS spectra was substantially lower than the number expected based on in silico
      analysis. CONCLUSIONS: The ability to confirm novel AS forms from MS/MS data in
      the dataset analyzed was found to be quite limited. This can be explained in part
      by low abundance of many novel transcripts, with the abundance of their
      corresponding protein products falling below the limit of detection by MS.

PMID- 21172050
TI  - A novel parametric approach to mine gene regulatory relationship from microarray
      datasets.
AB  - BACKGROUND: Microarray has been widely used to measure the gene expression level
      on the genome scale in the current decade. Many algorithms have been developed to
      reconstruct gene regulatory networks based on microarray data. Unfortunately,
      most of these models and algorithms focus on global properties of the expression
      of genes in regulatory networks. And few of them are able to offer intuitive
      parameters. We wonder whether some simple but basic characteristics of microarray
      datasets can be found to identify the potential gene regulatory relationship.
      RESULTS: Based on expression correlation, expression level variation and vectors
      derived from microarray expression levels, we first introduced several novel
      parameters to measure the characters of regulating gene pairs. Subsequently, we
      used the naive Bayesian network to integrate these features as well as the
      functional co-annotation between transcription factors and their target genes.
      Then, based on the character of time-delay from the expression profile, we were
      able to predict the existence and direction of the regulatory relationship
      respectively. CONCLUSIONS: Several novel parameters have been proposed and
      integrated to identify the regulatory relationship. This new model is proved to
      be of higher efficacy than that of individual features. It is believed that our
      parametric approach can serve as a fast approach for regulatory relationship
      mining.

PMID- 21172051
TI  - Sorting out inherent features of head-to-head gene pairs by evolutionary
      conservation.
AB  - BACKGROUND: A 'head-to-head' (h2h) gene pair is defined as a genomic locus in
      which two adjacent genes are divergently transcribed from opposite strands of
      DNA. In our previous work, this gene organization was found to be ancient and
      conserved, which subjects functionally related genes to transcriptional co
      regulation. However, some of the biological features of h2h pairs still need
      further clarification. RESULTS: In this work, we assorted human h2h pairs into
      four sequentially inclusive sets of gradually incremental conservation, and
      examined whether those previously asserted features were conserved or sharpened
      in the more conserved h2h pair sets in order to identify the inherent features of
      the h2h gene organization. The features of TSS distance, expression correlation
      within h2h pairs and among h2h genes, transcription factor association and
      functional similarities of h2h genes were examined. Our conservation-based
      analyses found that the bi-directional promoters of h2h gene pairs are most
      likely shorter than 100 bp; h2h gene pairs generally have only significant
      positive expression correlation but not negative correlation, and remarkably high
      positive expression correlations exist among h2h genes, as well as between h2h
      pairs observed in our previous study; h2h paired genes tend to share
      transcription factors. In addition, expression correlation of h2h pairs is
      positively related with the TF-sharing and functional coordination, while not
      related with TSS distance. CONCLUSIONS: Our findings remove the uncertainties of
      h2h genes about TSS distance, expression correlation and functional coordination,
      which provide insights into the study on the molecular mechanisms and functional
      consequences of the transcriptional regulation based on this special gene
      organization.

PMID- 21172052
TI  - Improved protein surface comparison and application to low-resolution protein
      structure data.
AB  - BACKGROUND: Recent advancements of experimental techniques for determining
      protein tertiary structures raise significant challenges for protein
      bioinformatics. With the number of known structures of unknown function expanding
      at a rapid pace, an urgent task is to provide reliable clues to their biological
      function on a large scale. Conventional approaches for structure comparison are
      not suitable for a real-time database search due to their slow speed. Moreover, a
      new challenge has arisen from recent techniques such as electron microscopy (EM),
      which provide low-resolution structure data. Previously, we have introduced a
      method for protein surface shape representation using the 3D Zernike descriptors
      (3DZDs). The 3DZD enables fast structure database searches, taking advantage of
      its rotation invariance and compact representation. The search results of protein
      surface represented with the 3DZD has showngood agreement with the existing
      structure classifications, but some discrepancies were also observed. RESULTS:
      The three new surface representations of backbone atoms, originally devised all
      atom-surface representation, and the combination of all-atom surface with the
      backbone representation are examined. All representations are encoded with the
      3DZD. Also, we have investigated the applicability of the 3DZD for searching
      protein EM density maps of varying resolutions. The surface representations are
      evaluated on structure retrieval using two existing classifications, SCOP and the
      CE-based classification. CONCLUSIONS: Overall, the 3DZDs representing backbone
      atoms show better retrieval performance than the original all-atom surface
      representation. The performance further improved when the two representations are
      combined. Moreover, we observed that the 3DZD is also powerful in comparing low
      resolution structures obtained by electron microscopy.

PMID- 21172054
TI  - Integer programming-based method for grammar-based tree compression and its
      application to pattern extraction of glycan tree structures.
AB  - BACKGROUND: A bisection-type algorithm for the grammar-based compression of tree
      structured data has been proposed recently. In this framework, an elementary
      ordered-tree grammar (EOTG) and an elementary unordered-tree grammar (EUTG) were
      defined, and an approximation algorithm was proposed. RESULTS: In this paper, we
      propose an integer programming-based method that finds the minimum context-free
      grammar (CFG) for a given string under the condition that at most two symbols
      appear on the right-hand side of each production rule. Next, we extend this
      method to find the minimum EOTG and EUTG grammars for given ordered and unordered
      trees, respectively. Then, we conduct computational experiments for the ordered
      and unordered artificial trees. Finally, we apply our methods to pattern
      extraction of glycan tree structures. CONCLUSIONS: We propose integer programming
      based methods that find the minimum CFG, EOTG, and EUTG for given strings,
      ordered and unordered trees. Our proposed methods for trees are useful for
      extracting patterns of glycan tree structures.

PMID- 21172053
TI  - Prior knowledge based mining functional modules from Yeast PPI networks with gene
      ontology.
AB  - BACKGROUND: In the literature, there are fruitful algorithmic approaches for
      identification functional modules in protein-protein interactions (PPI) networks.
      Because of accumulation of large-scale interaction data on multiple organisms and
      non-recording interaction data in the existing PPI database, it is still emergent
      to design novel computational techniques that can be able to correctly and
      scalably analyze interaction data sets. Indeed there are a number of large scale
      biological data sets providing indirect evidence for protein-protein interaction
      relationships. RESULTS: The main aim of this paper is to present a prior
      knowledge based mining strategy to identify functional modules from PPI networks
      with the aid of Gene Ontology. Higher similarity value in Gene Ontology means
      that two gene products are more functionally related to each other, so it is
      better to group such gene products into one functional module. We study (i) to
      encode the functional pairs into the existing PPI networks; and (ii) to use these
      functional pairs as pairwise constraints to supervise the existing functional
      module identification algorithms. Topology-based modularity metric and complex
      annotation in MIPs will be used to evaluate the identified functional modules by
      these two approaches. CONCLUSIONS: The experimental results on Yeast PPI networks
      and GO have shown that the prior knowledge based learning methods perform better
      than the existing algorithms.

PMID- 21172056
TI  - Herb network construction and co-module analysis for uncovering the combination
      rule of traditional Chinese herbal formulae.
AB  - BACKGROUND: Traditional Chinese Medicine (TCM) is characterized by the wide use
      of herbal formulae, which are capable of systematically treating diseases
      determined by interactions among various herbs. However, the combination rule of
      TCM herbal formulae remains a mystery due to the lack of appropriate methods.
      METHODS: From a network perspective, we established a method called Distance
      based Mutual Information Model (DMIM) to identify useful relationships among
      herbs in numerous herbal formulae. DMIM combines mutual information entropy and
      "between-herb-distance" to score herb interactions and construct herb network. To
      evaluate the efficacy of the DMIM-extracted herb network, we conducted in vitro
      assays to measure the activities of strongly connected herbs and herb pairs.
      Moreover, using the networked Liu-wei-di-huang (LWDH) formula as an example, we
      proposed a novel concept of "co-module" across herb-biomolecule-disease
      multilayer networks to explore the potential combination mechanism of herbal
      formulae. RESULTS: DMIM, when used for retrieving herb pairs, achieves a good
      balance among the herb's frequency, independence, and distance in herbal
      formulae. A herb network constructed by DMIM from 3865 Collaterals-related herbal
      formulae can not only nicely recover traditionally-defined herb pairs and
      formulae, but also generate novel anti-angiogenic herb ingredients (e.g.
      Vitexicarpin with IC50=3.2 MUM, and Timosaponin A-III with IC50=3.4 MUM) as well
      as herb pairs with synergistic or antagonistic effects. Based on gene and
      phenotype information associated with both LWDH herbs and LWDH-treated diseases,
      we found that LWDH-treated diseases show high phenotype similarity and identified
      certain "co-modules" enriched in cancer pathways and neuro-endocrine-immune
      pathways, which may be responsible for the action of treating different diseases
      by the same LWDH formula. CONCLUSIONS: DMIM is a powerful method to identify the
      combination rule of herbal formulae and lead to new discoveries. We also provide
      the first evidence that the co-module across multilayer networks may underlie the
      combination mechanism of herbal formulae and demonstrate the potential of network
      biology approaches in the studies of TCM.

PMID- 21172055
TI  - TF-centered downstream gene set enrichment analysis: Inference of causal
      regulators by integrating TF-DNA interactions and protein post-translational
      modifications information.
AB  - BACKGROUND: Inference of causal regulators responsible for gene expression
      changes under different conditions is of great importance but remains rather
      challenging. To date, most approaches use direct binding targets of transcription
      factors (TFs) to associate TFs with expression profiles. However, the low overlap
      between binding targets of a TF and the affected genes of the TF knockout limits
      the power of those methods. RESULTS: We developed a TF-centered downstream gene
      set enrichment analysis approach to identify potential causal regulators
      responsible for expression changes. We constructed hierarchical and multi-layer
      regulation models to derive possible downstream gene sets of a TF using not only
      TF-DNA interactions, but also, for the first time, post-translational
      modifications (PTM) information. We verified our method in one expression dataset
      of large-scale TF knockout and another dataset involving both TF knockout and TF
      overexpression. Compared with the flat model using TF-DNA interactions alone, our
      method correctly identified five more actual perturbed TFs in large-scale TF
      knockout data and six more perturbed TFs in overexpression data. Potential
      regulatory pathways downstream of three perturbed regulators- SNF1, AFT1 and SUT1
      -were given to demonstrate the power of multilayer regulation models integrating
      TF-DNA interactions and PTM information. Additionally, our method successfully
      identified known important TFs and inferred some novel potential TFs involved in
      the transition from fermentative to glycerol-based respiratory growth and in the
      pheromone response. Downstream regulation pathways of SUT1 and AFT1 were also
      supported by the mRNA and/or phosphorylation changes of their mediating TFs
      and/or "modulator" proteins. CONCLUSIONS: The results suggest that in addition to
      direct transcription, indirect transcription and post-translational regulation
      are also responsible for the effects of TFs perturbation, especially for TFs
      overexpression. Many TFs inferred by our method are supported by literature.
      Multiple TF regulation models could lead to new hypotheses for future
      experiments. Our method provides a valuable framework for analyzing gene
      expression data to identify causal regulators in the context of TF-DNA
      interactions and PTM information.

PMID- 21172057
TI  - Gene-centric association analysis for the correlation between the guanine
      cytosine content levels and temperature range conditions of prokaryotic species.
AB  - BACKGROUND: The environment has been playing an instrumental role in shaping and
      maintaining the morphological, physiological and biochemical diversities of
      prokaryotes. It has been debatable whether the whole-genome Guanine-Cytosine (GC)
      content levels of prokaryotic organisms are correlated with their optimal growth
      temperatures. Since the GC content is variable within a genome, we here focus on
      the correlation between the genic GC content levels and the temperature range
      conditions of prokaryotic organisms. RESULTS: The GC content levels in the coding
      regions of four genes were consistently identified as correlated with the
      temperature range condition when the association analysis was applied to (i) the
      722 mesophilic and 93 thermophilic/hyperthermophilic organisms regardless of
      their phylogeny, oxygen requirement, salinity, or habitat conditions, and (ii)
      partial lists of organisms when organisms with certain phylogeny, oxygen
      requirement, salinity or habitat conditions were excluded. These four genes are
      K01251 (adenosylhomocysteinase), K03724 (DNA repair and recombination proteins),
      K07588 (LAO/AO transport system kinase), and K09122 (hypothetical protein).To
      further validate the identified correlation relationships, we examined to what
      extent the temperature range condition of an organism can be predicted based on
      the GC content levels in the coding regions of the selected genes. The 84.52%
      accuracy for the complete genomes, the 84.09% accuracy for the in-progress
      genomes, and 82.70% accuracy for the metagenomes, especially when being compared
      to the 50% accuracy rendered by random guessing, suggested that the temperature
      range condition of a prokaryotic organism can generally be predicted based on the
      GC content levels of the selected genomic regions. CONCLUSIONS: The results
      rendered by various statistical tests and prediction tests indicated that the GC
      content levels of the coding/non-coding regions of certain genes are highly
      likely to be correlated with the temperature range conditions of prokaryotic
      organisms. Therefore, it is promising to carry out "reverse ecology" and to
      complete the ecological characterizations of prokaryotic organisms, i.e., to
      infer their temperature range conditions based on the GC content levels of
      certain genomic regions.

PMID- 21172058
TI  - RecMotif: a novel fast algorithm for weak motif discovery.
AB  - BACKGROUND: Weak motif discovery in DNA sequences is an important but unresolved
      problem in computational biology. Previous algorithms that aimed to solve the
      problem usually require a large amount of memory or execution time. In this
      paper, we proposed a fast and memory efficient algorithm, RecMotif, which
      guarantees to discover all motifs with specific (l, d) settings (where l is the
      motif length and d is the maximum number of mutations between a motif instance
      and the true motif). RESULTS: Comparisons with several recently proposed
      algorithms have shown that RecMotif is more scalable for handling longer and
      weaker motifs. For instance, it can solve the open challenge cases such as (40,
      14) within 5 hours while the other algorithms compared failed due to either
      longer execution times or shortage of memory space. For real biological
      sequences, such as E.coli CRP, RecMotif is able to accurately discover the motif
      instances with (l, d) as (18, 6) in less than 1 second, which is faster than the
      other algorithms compared. CONCLUSIONS: RecMotif is a novel algorithm that
      requires only a space complexity of O(m2n) (where m is the number of sequences in
      the data and n is the length of the sequences).

PMID- 21172060
TI  - Predictive diagnostics and personalized medicine for the prevention of chronic
      degenerative diseases.
AB  - Progressive increase of mean age and life expectancy in both industrialized and
      emerging societies parallels an increment of chronic degenerative diseases (CDD)
      such as cancer, cardiovascular, autoimmune or neurodegenerative diseases among
      the elderly. CDD are of complex diagnosis, difficult to treat and absorbing an
      increasing proportion in the health care budgets worldwide. However, recent
      development in modern medicine especially in genetics, proteomics, and
      informatics is leading to the discovery of biomarkers associated with different
      CDD that can be used as indicator of disease's risk in healthy subjects.
      Therefore, predictive medicine is merging and medical doctors may for the first
      time anticipate the deleterious effect of CDD and use markers to identify persons
      with high risk of developing a given CDD before the clinical manifestation of the
      diseases. This innovative approach may offer substantial advantages, since the
      promise of personalized medicine is to preserve individual health in people with
      high risk by starting early treatment or prevention protocols. The pathway is now
      open, however the road to an effective personalized medicine is still long,
      several (diagnostic) predictive instruments for different CDD are under
      development, some ethical issues have to be solved. Operative proposals for the
      heath care systems are now needed to verify potential benefits of predictive
      medicine in the clinical practice. In fact, predictive diagnostics, personalized
      medicine and personalized therapy have the potential of changing classical
      approaches of modern medicine to CDD.

PMID- 21172059
TI  - Large number of phosphotransferase genes in the Clostridium beijerinckii NCIMB
      8052 genome and the study on their evolution.
AB  - BACKGROUND: Clostridium beijerinckii is a valuable bacteria species which has the
      ability of ABE (acetone, butanol and ethanol) production. It has been shown that
      Phosphotransferase (PTS) is an important and common system for both carbohydrate
      uptake and phosphorylation in bacteria, but detailed study of the system,
      especially its fructose/mannose/sorbose family is scant. RESULTS: In the genome
      of Clostridium beijerinckii NCIMB 8052, a model strain recently sequenced, there
      are large number of PTS genes, among them 9 complete sets belong to the
      fructose/mannose/sorbose family of its enzyme II complex. Our study, based on
      evidences provided by phylogenetic relationship, analyses of gene contents and
      clusters, as well as synteny examination, indicates that it is possible to
      further classify this PTS family into three sub-groups, which are corresponding
      to the three sugar substrates. Furthermore, we proposed a model how these PTS
      systems are evolved in bacteria. CONCLUSION: This work may explain the
      experimental result that Clostridium beijerinckii NCIMB 8052 can better utilize
      fructose as substrate, thus could lead to a better understanding of the ABE
      producing mechanism in Clostridium beijerinckii and other microbial species. It
      may help to illustrate a higher butanol-productivity future.

PMID- 21172062
TI  - Artificial Adaptive Systems and predictive medicine: a revolutionary paradigm
      shift.
AB  - An individual patient is not the average representative of the population. Rather
      he or she is a person with unique characteristics. An intervention may be
      effective for a population but not necessarily for the individual patient. The
      recommendation of a guideline may not be right for a particular patient because
      it is not what he or she wants, and implementing the recommendation will not
      necessarily mean a favourable outcome.The author will describe a reconfiguration
      of medical thought which originates from non linear dynamics and chaos theory.
      The coupling of computer science and these new theoretical bases coming from
      complex systems mathematics allows the creation of "intelligent" agents able to
      adapt themselves dynamically to problem of high complexity: the Artificial
      Adaptive Systems, which include Artificial Neural Networks( ANNs ) and
      Evolutionary Algorithms ( EA).ANNs and EA are able to reproduce the dynamical
      interaction of multiple factors simultaneously, allowing the study of complexity;
      they can also help medical doctors in making decisions under extreme uncertainty
      and to draw conclusions on individual basis and not as average trends. These
      tools can allow a more efficient Technology Transfer from the Science of Medicine
      to the Real World overcoming many obstacles responsible for the present
      translational failure. They also contribute to a new holistic vision of the human
      subject contrasting the statistical reductionism which tends to squeeze or even
      delete the single subject sacrificing him to his group of belongingness. A
      remarkable contribution to this individual approach comes from Fuzzy Logic,
      according to which there are no sharp limits between opposite things, like health
      and disease. This approach allows to partially escape from probability theory
      trap in situations where is fundamental to express a judgment based on a single
      case and favours a novel humanism directed to the management of the patient as
      individual subject.

PMID- 21172061
TI  - The conselice study of brain ageing.
AB  - Among the age-related diseases, the development of cognitive impairments, in
      particular dementia, is the most devastating for the individual and has great
      social and healthcare costs. Accurate information is needed about the prevalence
      and incidence of cognitive disorders and the physiology of the ageing brain. In
      particular, only scant data are available about the relationship between ageing,
      cognitive status and nutritional factors. In order to address these issues we
      planned the Conselice Study of Brain Ageing, a longitudinal study of physiologic
      and pathologic brain ageing. The center involved in the study was the
      municipality of Conselice, Ravenna province, in the Northern Italian region
      Emilia-Romagna. A total of 1016 subjects aged 65 and over was enrolled at
      baseline. Information about cognitive status at 4-years of follow-up was
      collected for 940 of them. These data have been used to estimate prevalence and
      incidence of dementia in the elderly Italian population and to investigate the
      possible role of baseline blood homocysteine as risk factors for dementia.

PMID- 21172063
TI  - Multi factorial interactions in the pathogenesis pathway of Alzheimer's disease:
      a new risk charts for prevention of dementia.
AB  - BACKGROUND: The population longitudinal study named "The Conselice Study" has
      been the focus of the present investigation. 65 years old or older participants
      of this population study on brain aging were followed up for 5 years: 937
      subjects completed the follow-up. Relationships of 46 genetic, phenotypic,
      clinical and nutritional factors on incident cognitive decline and incident
      dementia cases were investigated. RESULTS: A new statistical approach, called the
      Auto Contractive Map (AutoCM) was applied to find relationship between variables
      and a possible hierarchy in the relevance of each variable with incident
      dementia. This method, based on an artificial adaptive system, was able to define
      the association strength of each variable with all the others. Moreover, few
      variables resulted to be aggregation points in the variable connectivity map
      related to cognitive decline and dementia. Gene variants and cognate phenotypic
      variables showed differential degrees of relevance to brain aging and dementia. A
      risk map for age associated cognitive decline and dementia has been constructed
      and will be presented and discussed. CONCLUSION: This map of variables may be use
      to identify subjects with increased risk of developing cognitive decline end/or
      dementia and provide pivotal information for early intervention protocols for
      prevention of dementia.

PMID- 21172064
TI  - Signal transduction in neurons: effects of cellular prion protein on fyn kinase
      and ERK1/2 kinase.
AB  - BACKGROUND: It has been reported that cellular prion protein (PrPc) co-localizes
      with caveolin-1 and participates to signal transduction events by recruiting Fyn
      kinase. As PrPc is a secreted protein anchored to the outer surface membrane
      through a glycosylphosphatidylinositol (GPI) anchor (secPrP) and caveolin-1 is
      located in the inner leaflet of plasma membrane, there is a problem of how the
      two proteins can physically interact each other and transduce signals. RESULTS:
      By using the GST-fusion proteins system we observed that PrPc strongly interacts
      with caveolin-1 scaffolding domain and with a caveolin-1 hydrophilic C-terminal
      region, but not with the caveolin-1 N-terminal region. In vitro binding
      experiments were also performed to define the site(s) of PrPc interacting with
      cav-1. The results are consistent with a participation of PrPc octapeptide
      repeats motif in the binding to caveolin-1 scaffolding domain. The caveolar
      localization of PrPc was ascertained by co-immunoprecipitation, by co
      localization after flotation in density gradients and by confocal microscopy
      analysis of PrPc and caveolin-1 distributions in a neuronal cell line (GN11)
      expressing caveolin-1 at high levels. CONCLUSIONS: We observed that, after
      antibody-mediated cross-linking or copper treatment, PrPc was internalized
      probably into caveolae. We propose that following translocation from rafts to
      caveolae or caveolae-like domains, secPrP could interact with caveolin-1 and
      induce signal transduction events.

PMID- 21172066
TI  - Serum neutrophil gelatinase-B associated lipocalin (NGAL) levels in Down's
      syndrome patients.
AB  - Neutrophil gelatinase-associated lipocalin (NGAL) is a group of proteins with
      different functions.NGAL is released by different cell types such as epithelial
      cell, hepatocytes and renal tubular cells during inflammation and after cell
      injury. Expression of NGAL is induced under various pathophysiological conditions
      such as infection, cancer, inflammation, kidney injury, cardiovascular disease,
      burn injury, and intoxication, which has an important anti-apoptotic and anti
      inflammatory role.Subjects with Down's syndrome (DS) are affected by many
      pathological age related conditions such as mental retardation, Alzheimer's
      disease, immune defects and increased susceptibility to infections. The aim of
      this study is to evaluate possible use of NGAL as a marker of inflammatory status
      for allow an early diagnosis of inflammatory disease such as autoimmune disease
      in DS patients, that are more susceptible to these pathologies, especially in
      elderly subjects.In this study were recruited 3 groups of DS subjects (children,
      adults and elderly) and compared them to healthy control group.The molecules of
      interest was determinated by immuno-enzymatic assay (ELISA).Our results show that
      NGAL plasmatic level was significantly higher in DS patients compared to healthy
      controls. Moreover NGAL levels increase in correlation with the age, and showed a
      significantly correlation between the increase with the severity of disease.DS is
      characterized by an enhancement of gene production such as GART, SOD-1 and CBS
      that encode specific protein and enzyme involved in hydrogen peroxide and
      superoxide production, species highly cytotoxic implicated in inflammation and
      ageing.NGAL may have the potential application to ameliorate the toxicity induced
      by oxidative stress conditions such as Alzheimer's disease, thalassemia,
      cardiovascular disease, burn injury, transplantation, diabetes, and aging.

PMID- 21172065
TI  - Altered glycosylation profile of purified plasma ACT from Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is one of the most frequent cause of
      neurodegenerative disorder in the elderly. Inflammation has been implicated in
      brain degenerative processes and peripheral markers of brain AD related
      impairment would be useful. Plasma levels of alpha-1-antichymotrypsin (ACT), an
      acute phase protein and a secondary component of amyloid plaques, are often
      increased in AD patients and high blood ACT levels correlate with progressive
      cognitive deterioration. During inflammatory responses changes in the micro
      heterogeneity of ACT sugar chains have been described. METHODS: N-Glycanase
      digestion from Flavobacterium meningosepticum (PNGase F) was performed on both
      native and denatured purified ACT condition and resolved to Western blot with the
      purpose to revealed the ACT de-glycosylation pattern.Further characterization of
      the ACT glycan profile was obtained by a glycoarray; each lectin group in the
      assay specifically recognizes one or two glycans/epitopes. Lectin-bound ACT
      produced a glyco-fingerprint and mayor differences between AD and controls
      samples were assessed by a specific algorithms. RESULTS: Western blot analysis of
      purified ACT after PNGase F treatment and analysis of sugar composition of ACT
      showed significantly difference in "glyco-fingerprints" patterns from controls
      (CTR) and AD; ACT from AD showing significantly reduced levels of sialic acid. A
      difference in terminal GlcNac residues appeared to be related with progressive
      cognitive deterioration. CONCLUSIONS: Low content of terminal GlcNac and sialic
      acid in peripheral ACT in AD patients suggests that a different pattern of
      glycosylation might be a marker of brain inflammation. Moreover ACT glycosylation
      analysis could be used to predict AD clinical progression and used in clinical
      trials as surrogate marker of clinical efficacy.

PMID- 21172067
TI  - Prevention of bone metastases and management of bone health in early breast
      cancer.
AB  - Treatment options for women with early-stage breast cancer have never been
      better, and the addition of bisphosphonates to adjuvant therapy is a valuable new
      tool capable of substantially improving clinical outcomes for these women.
      Several recent studies demonstrated that the anticancer activity of
      bisphosphonates is not limited to bone, and can translate into a reduction in
      disease recurrence, including reductions in locoregional and distant metastases.
      In addition, bisphosphonates maintain bone health during adjuvant therapy; this
      may be especially important for women who are at high risk for fracture.

PMID- 21172068
TI  - Basal-like breast cancers: the phenotypic disparity between the cancer-initiating
      cells and tumor histology.
AB  - Recent evidence suggests that a rare-cell population with a stem cell phenotype
      maintains breast tumors. Therefore, to devise breast cancer therapies that are
      more effective, we need to understand the unique biology of these cancer stem
      cells. Currently, very little is known about the origin of cancer stem cells and
      their relationship to the tumor phenotype. A recent study from Smalley's group
      demonstrates that targeting an inactivating Brca1 mutation to the luminal
      progenitors could yield basal-like breast cancers. This observation suggests that
      the inherent plasticity of the primitive cells can be hijacked by the tumorigenic
      processes to produce tumors with an unpredictable phenotype.

PMID- 21172069
TI  - Addressing the challenges to successful recruitment and retention in Alzheimer's
      disease clinical trials.
AB  - Among the key challenges in Alzheimer's disease drug development is the timely
      completion of clinical trials. Unfortunately, clinical trials often suffer from
      slow or insufficient enrollment. Successful clinical trial recruitment describes
      a balance between expeditiously achieving full enrollment and ensuring an
      appropriate study sample. Investigators face a number of challenges to the
      successful negotiation of this balance. The failure to address these challenges
      means that drug development may take more time and money and that trial results
      may not adequately represent drug efficacy or may not be applicable beyond the
      study. We review the challenges to recruitment and retention in Alzheimer's
      disease clinical trials and present a framework to address them.

PMID- 21172070
TI  - Using pulse pressure variation or stroke volume variation to diagnose right
      ventricular failure?

PMID- 21172071
TI  - Controversies in breast cancer 2010.

PMID- 21172072
TI  - The emerging breast cancer epidemic: early diagnosis and treatment.

PMID- 21172073
TI  - Emerging breast cancer epidemic: impact on palliative care.

PMID- 21172074
TI  - Introduction to session on undue and disproportionate influences.

PMID- 21172075
TI  - Classical peer review: an empty gun.

PMID- 21172076
TI  - Randomized adjuvant trials in oncology: a necessity or time-consuming luxury?

PMID- 21172077
TI  - Controversies in Breast Cancer 2010. Session 6 introduction.

PMID- 21172078
TI  - Designing adjuvant treatment based on biological measurements in the neoadjuvant
      setting.

PMID- 21172080
TI  - Do selective serotonin receptor inhibitor antidepressants reduce tamoxifen's
      effectiveness and increase the risk of death from breast cancer?

PMID- 21172079
TI  - Genome-wide case-control study of musculoskeletal adverse events and functional
      genomics in women receiving aromatase inhibitors: going beyond associations.

PMID- 21172082
TI  - Predictive and prognostic factors.

PMID- 21172081
TI  - Angiogenesis - still a worthwhile target for breast cancer therapy?

PMID- 21172083
TI  - Introduction: are current drug development programmes realising the full
      potential of new agents?

PMID- 21172084
TI  - Deciding priorities in Pharma.

PMID- 21172085
TI  - Deciding priorities in a clinical studies group.

PMID- 21172086
TI  - Are current development programs realising the full potential of new agents?

PMID- 21172087
TI  - Contribution of biomarkers to personalized medicine.

PMID- 21172088
TI  - Systems pathology.

PMID- 21172089
TI  - Molecular profiling currently offers no more than tumour morphology and basic
      immunohistochemistry.

PMID- 21172090
TI  - Molecular profiling contributes more than routine histology and
      immonohistochemistry to breast cancer diagnostics.

PMID- 21172091
TI  - The globalisation of breast cancer.

PMID- 21172092
TI  - Emerging breast cancer epidemic: evidence from Africa.

PMID- 21172093
TI  - Breast cancer prevention in the developing world.

PMID- 21172094
TI  - Excess mortality from chronic physical disease in psychiatric patients-the
      forgotten problem.

PMID- 21172095
TI  - The epidemiology of excess mortality in people with mental illness.
AB  - OBJECTIVE: to investigate the burden of excess mortality among people with mental
      illness in developed countries, how it is distributed, and whether it has changed
      over time. METHOD: we conducted a systematic search of MEDLINE, restricting our
      attention to peer-reviewed studies and reviews published in English relating to
      mortality and mental illness. Because of the large number of studies that have
      been undertaken during the last 30 years, we have selected a representative cross
      section of studies for inclusion in our review. RESULTS: there is substantial
      excess mortality in people with mental illness for almost all psychiatric
      disorders and all main causes of death. Consistently elevated rates have been
      observed across settings and over time. The highest numbers of excess deaths are
      due to cardiovascular and respiratory diseases. With life expectancy increasing
      in the general population, the disparity in mortality outcomes for people with
      mental illness is increasing. CONCLUSIONS: without the development of alternative
      approaches to promoting and treating the physical health of people with mental
      illness, it is possible that the disparity in mortality outcomes will persist.

PMID- 21172096
TI  - Schizophrenia and cancer: in 2010 do we understand the connection?
AB  - OBJECTIVE: in recent years, there has been a plethora of cancer mortality and
      incidence data reported in schizophrenia. Despite this, there has been little
      focus on cancer in schizophrenia guidelines. Additionally, there have been
      suggestions that schizophrenia may provide inherent protection against cancer.
      The goal of this review is to establish, using recent data, the incidence and
      mortality rates for cancer in schizophrenia. METHOD: we identified systematic
      reviews and meta-analyses and undertook a search using the Medical Subject
      Headings' entry terms schizophrenia and neoplasm. RESULTS: incidence and
      mortality rates for cancer in schizophrenia are increased, compared with relevant
      general populations. Data are not uniformly reported and cohort ages tend to be
      young for expected cancer incidence. Despite the young cohort ages, the incidence
      of the major cancers-lung and breast-are substantially increased. Confounders are
      often not measured in the epidemiologic databases. When lung cancer is adjusted
      for smoking rates, there appears to be a lower risk of lung cancer than expected
      providing some basis to support an inherently reduced risk of cancer. There may
      also be a dissonance between incidence and mortality rates that suggest a
      prejudice against either diagnosis or treatment of these vulnerable patients.
      CONCLUSION: a single definitive study of schizophrenia and cancer is unfeasible,
      and future research will lean heavily on systematic review and meta-analysis.
      Researchers should report cancer data to include age and follow-up data and
      cohort overlap. Cancer accounts for almost an equivalent mortality as
      cardiovascular disease.

PMID- 21172097
TI  - The relation between disease severity and cost of caring for patients with
      Alzheimer disease in Canada.
AB  - OBJECTIVES: to characterize the cost of caring for an outpatient in Canada with
      Alzheimer disease (AD) based on disease severity, and to describe how costs
      change with increases in disease severity. METHOD: community-dwelling patients
      with mild-to-moderate AD were enrolled in a 3-year, naturalistic, observational
      study. Assessments included cognition (Mini Mental Status Examination), global
      ratings (Global Deterioration Scale [GDS]), and daily function (Functional
      Autonomy Measurement System) as part of the Canadian Outcomes Study in Dementia.
      Direct (medical and nonmedical) and indirect costs were collected using resource
      use questionnaires. Costs at baseline were compared with costs at follow-up and
      correlated with disease severity. RESULTS: total costs associated with treating
      AD were significantly higher with greater disease severity. The mean total cost
      to treat patients with very mild AD (GDS = 2) was $367 per month, compared with
      $4063 per month for patients with severe or very severe AD (GDS = 6). From
      baseline to follow-up, the greatest changes in cost were observed in the group of
      patients with the most severe AD as measured by all scales. The largest component
      of total cost was indirect costs at most severity levels, though medication costs
      contributed the most in patients with very mild AD. Significant independent
      contributors to cost were being female, having more impaired activities of daily
      living, and exhibiting more neuropsychiatric symptoms. CONCLUSIONS: costs for
      treating a patient with AD were strongly associated with disease severity, even
      though none of the patients were institutionalized. Delaying the progression of
      AD may reduce indirect costs and burden to caregivers.

PMID- 21172099
TI  - Anxiety disorders among offenders with antisocial personality disorders: a
      distinct subtype?
AB  - OBJECTIVES: about 50% of men with antisocial personality disorder (APD) present a
      comorbid anxiety disorder. Historically, it was thought that anxiety limited
      criminal activity and the development of APD, but recent evidence suggests that
      heightened responsiveness to threat may lead to persistent violent behaviour. Our
      study aimed to determine the prevalence of APD comorbid with anxiety disorders
      among offenders and the association of these comorbid disorders with violent
      offending. METHOD: a random sample of 495 male penitentiary inmates completed an
      interview using the Diagnostic Interview Schedule. After excluding men with
      psychotic disorders, 279 with APD were retained. All authorized access to their
      criminal records. RESULTS: two-thirds of the prisoners with APD presented a
      lifetime anxiety disorder. Among them, one-half had the onset of their anxiety
      disorder before they were aged 16 years. Among the offenders with APD, those
      with, compared with those without, anxiety disorders presented significantly more
      symptoms of APD, were more likely to have begun their criminal careers before
      they were aged 15 years, to have diagnoses of alcohol and (or) drug abuse and
      (or) dependence, and to have experienced suicidal ideas and attempts. While there
      were no differences in the mean number of convictions for violent offences
      between APD prisoners with and without anxiety disorders, more of those with
      anxiety disorders had been convicted of serious crimes involving interpersonal
      violence. CONCLUSIONS: among men with APD, a substantial subgroup present life
      long anxiety disorders. This pattern of comorbidity may reflect a distinct
      mechanism underlying violent behaviour and signalling the need for specific
      treatments.

PMID- 21172098
TI  - Time trends in mortality associated with depression: findings from the Stirling
      County study.
AB  - OBJECTIVE: to address the question of whether a mortality risk associated with
      depression in a 1952 representative sample of Stirling County adults changed in a
      new sample in 1970, and whether there was a change in associations with cigarette
      smoking and alcoholism. METHOD: sample members were interviewed about depression
      and cigarette smoking. General physicians were interviewed by psychiatrists
      regarding alcoholism. Information about death as of December 31, 1992, was
      provided by Statistics Canada. Proportional hazards models were fitted in the 2
      samples to assess the mortality risks associated with depression among men and
      women during 20 years of follow-up, and additionally among men with heavy smoking
      and alcoholism. Specific causes of death were investigated. RESULTS: hazard
      ratios representing the association between depression and premature death among
      men were 2.6 (95% CI 1.4 to 4.9) and 2.8 (95% CI 1.5 to 5.1), respectively, in
      the 1952 and 1970 samples for the first 10 years of follow-up. Hazard ratios for
      women were 1.4 (95% CI 0.6 to 3.2) and 1.2 (95% CI 0.5 to 2.9). The risk
      associated with depression among men was independent of alcoholism and heavy
      smoking. Depression and alcoholism were significantly associated with death by
      external causes and circulatory disease; heavy smoking was significantly
      associated with malignant neoplasms. CONCLUSION: the mortality associated with
      depression did not change during the period from 1952 to 1970. Depressed men
      experienced a significant mortality risk that was not matched among depressed
      women and also was not due to alcoholism and heavy smoking.

PMID- 21172101
TI  - [Psychometric properties of the French version of the Guilt Inventory].
AB  - OBJECTIVE: the feeling of guilt is essential to a interpersonal functioning but
      can also play a role in self-destructive. Although there is about 20 guilt scales
      in English, none has yet been validated in French. This study intends to fill
      this gap by proposing a French version of the Guilt Inventory (GI) that evaluates
      trait guilt, state guilt, and moral standards. METHOD: seven hundred and thirty
      eight students filled GI in French as well as scales measuring trait anxiety and
      state anxiety, and empathy skills. In a sample subgroup, we also evaluated
      depression, social desirability, and personality factors. RESULTS: an exploratory
      factor analysis conducted on half of the participants resulted in keeping 18 of
      20 items in trait GI, and 9 of 10 items in state GI, but also in disregarding the
      moral standard scale. A confirmatory factor analysis performed on the sample
      other half has validated this two-factor structure. The expected correlations
      between guilt scores, negative affectivity and interpersonal functioning were
      observed. CONCLUSION: this study suggests that the GI French version is an
      adequate measure of trait guilt and state guilt, and could prove to be a useful
      tool for both research and clinical purposes.

PMID- 21172100
TI  - Pharmacoepidemiology of benzodiazepine and sedative-hypnotic use in a Canadian
      general population cohort during 12 years of follow-up.
AB  - OBJECTIVE: benzodiazepines (BDZs) and similar sedative-hypnotics (SSHs) can have
      both beneficial and adverse effects. Clinical practice guidelines indicate that
      the course of treatment should usually be brief (a few weeks), but patients often
      take these medications for longer periods of time. We hypothesized that treatment
      with antidepressants (ADs) would be associated with a shorter duration of SSHs
      use as mood and anxiety disorders may underlie the symptoms usually targeted by
      BDZ treatment. METHOD: our study used data from a Canadian longitudinal general
      health study, the National Population Health Survey, which has collected data
      since 1994. Data are currently available to 2006. At each interview, all
      medications taken in the preceding 2 days are recorded. In our study, we used
      proportional hazard models to describe patterns of initiation and discontinuation
      of these medications in the general population. RESULTS: at each interview, the
      frequency of BDZ-SSH use was 2% to 3%. About 1% of the population initiated use
      in each 2-year follow-up period. Contrary to expectation, taking ADs predicted
      initiation of BDZ-SSHs, but not discontinuation. CONCLUSIONS: unexpectedly,
      respondents taking ADs had a higher frequency of new BDZ-SSH use. AD use may be a
      marker for depression severity or comorbidity, such that the observed results may
      be an artifact of confounding by these factors. Irrespective of etiology,
      initiation of AD treatment does not appear to negate the risk of long-term BDZ
      SSH use.

PMID- 21172103
TI  - Is open urologic surgery a lost skill in this era of minimally invasive urologic
      malady management?

PMID- 21172102
TI  - Alcohol use and pregnancy consensus clinical guidelines.
AB  - OBJECTIVE: to establish national standards of care for the screening and
      recording of alcohol use and counselling on alcohol use of women of child-bearing
      age and pregnant women based on the most up-to-date evidence. EVIDENCE: published
      literature was retrieved through searches of PubMed, CINAHL, and the Cochrane
      Library in May 2009 using appropriate controlled vocabulary (e.g., pregnancy
      complications, alcohol drinking, prenatal care) and key words (e.g., pregnancy,
      alcohol consumption, risk reduction). Results were restricted to literature
      published in the last five years with the following research designs: systematic
      reviews, randomized control trials/controlled clinical trials, and observational
      studies. There were no language restrictions. Searches were updated on a regular
      basis and incorporated in the guideline to May 2010. Grey (unpublished)
      literature was identified through searching the websites of health technology
      assessment (HTA) and HTA-related agencies, national and international medical
      specialty societies, clinical practice guideline collections, and clinical trial
      registries. Each article was screened for relevance and the full text acquired if
      determined to be relevant. The evidence obtained was reviewed and evaluated by
      the members of the Expert Workgroup established by the Society of Obstetricians
      and Gynaecologists of Canada. The quality of evidence was evaluated and
      recommendations were made according to guidelines developed by the Canadian Task
      Force on Preventive Health Care. VALUES: the quality of evidence was rated using
      the criteria described by the Canadian Task Force on Preventive Health Care
      (Table 1). SPONSOR: the Public Health Agency of Canada and the Society of
      Obstetricians and Gynaecologists of Canada. ENDORSEMENT: these consensus
      guidelines have been endorsed by the Association of Obstetricians and
      Gynecologists of Quebec; the Canadian Association of Midwives; the Canadian
      Association of Perinatal, Women's Health and Neonatal Nurses (CAPWHN); the
      College of Family Physicians of Canada; the Federation of Medical Women of
      Canada; the Society of Rural Physicians of Canada; and Motherisk. SUMMARY
      STATEMENTS: 1. There is evidence that alcohol consumption in pregnancy can cause
      fetal harm. (II-2) There is insufficient evidence regarding fetal safety or harm
      at low levels of alcohol consumption in pregnancy. (III) 2. There is insufficient
      evidence to define any threshold for low-level drinking in pregnancy. (III) 3.
      Abstinence is the prudent choice for a woman who is or might become pregnant.
      (III) 4. Intensive culture-, gender-, and family-appropriate interventions need
      to be available and accessible for women with problematic drinking and/or alcohol
      dependence. (II-2). RECOMMENDATIONS: 1. Universal screening for alcohol
      consumption should be done periodically for all pregnant women and women of child
      bearing age. Ideally, at-risk drinking could be identified before pregnancy,
      allowing for change. (II-2B) 2. Health care providers should create a safe
      environment for women to report alcohol consumption. (III-A) 3. The public should
      be informed that alcohol screening and support for women at risk is part of
      routine women's health care. (III-A) 4. Health care providers should be aware of
      the risk factors associated with alcohol use in women of reproductive age. (III
      B) 5. Brief interventions are effective and should be provided by health care
      providers for women with at-risk drinking. (II-2B) 6. If a woman continues to use
      alcohol during pregnancy, harm reduction/treatment strategies should be
      encouraged. (II-2B) 7. Pregnant women should be given priority access to
      withdrawal management and treatment. (III-A) 8. Health care providers should
      advise women that low-level consumption of alcohol in early pregnancy is not an
      indication for termination of pregnancy. (II-2A).

PMID- 21172104
TI  - Legends in urology.

PMID- 21172105
TI  - Active surveillance for prostate cancer in a veteran population.
AB  - INTRODUCTION: Active surveillance for prostate cancer is a therapeutic option
      which is gaining more popularity. Implicit in this approach is careful monitoring
      to identify those with progression. Criteria for placing patients on active
      surveillance vary but generally include Gleason sum of 6 or less, prostate
      specific antigen (PSA) less than 20, and a small volume of cancer in the biopsy
      specimen. We review our experience with active surveillance in a veteran
      population. MATERIALS AND METHODS: We conducted a retrospective review of
      patients from the Kansas City Veterans Affairs (KCVA) who met the requirements
      for active surveillance (Gleason sum 6, percent of cancer in the specimen less
      than 20%, and PSA less than 20 ng/dL) between January 2004 and December 2009. In
      the patient group who chose active surveillance (AS), we evaluated the rates of
      compliance with the protocol mandated PSA's and the 1 year biopsy. In the patient
      group who declined AS and underwent immediate prostatectomy, we reviewed the
      final pathology for stage, Gleason grade, percent of tissue involved with cancer,
      margin status, nodal status, and rates of biochemical recurrence. RESULTS: We
      identified 207 patients who met the requirements for active surveillance. Of
      these patients, 45 patients chose active surveillance while 66 patients underwent
      immediate radical prostatectomy at the KCVA. Of the 45 patients who went on
      active surveillance, all participants had at least one PSA drawn. However, only
      24 (53.3%) patients complied with the protocol mandated prostate biopsy at 1
      year. In the patient group who chose to undergo an immediate prostatectomy, 43 of
      66 (65.2%) patients had upgrading of their Gleason score. This included 12
      patients upgraded to Gleason sum 8 to 10 and two patients who were upstaged to T3
      disease. Despite the significant upgrading, only two patients have had a
      biochemical recurrence at a median follow up of 30 months. CONCLUSIONS: Active
      surveillance is a viable option for patients with low risk prostate cancer.
      However, this study raises concerns about compliance with recommendations for
      active surveillance in a VA population. Furthermore, there was a significant risk
      in this study of under-grading in patients who underwent immediate prostatectomy.
      This emphasizes the need for better education of patients who enter into active
      surveillance protocols regarding the need for compliance, the risks of
      progression, and the chance of under grading.

PMID- 21172106
TI  - Practice patterns for post-prostatectomy hormonal therapy amongst Canadian
      radiation oncologists.
AB  - INTRODUCTION: Level 1 evidence demonstrates the benefit of postoperative
      radiotherapy (PORT) for pT3 disease and positive margins. The role of androgen
      deprivation therapy (ADT) after PORT remains to be defined from results of
      ongoing randomized trials. This study was undertaken to determine the factors
      influencing the current use of ADT after PORT amongst Canadian radiation
      oncologists. METHODS: An institutional survey was emailed to the Genito-urinary
      Radiation Oncologists Group of Canada (GUROC), designed to assess the likelihood
      of prescribing ADT in early and delayed PORT scenarios with variations in disease
      prognosticators. Analysis used descriptive statistics. RESULTS: Majority (94%) do
      not routinely advocate ADT with PORT. With early PORT and undetectable prostate
      specific antigen (PSA), respondents (n = 53) indicated that Gleason Score 8-10
      (89%), pT3b disease (80%) and high risk D'Amico category (76%) were important
      considerations. With early PORT and a detectible PSA, important considerations
      were PSA doubling time (90%), high risk disease (85%), pT3b category (82%) and
      time to relapse (TTR) of < 3 months (90%). Similar patterns were observed in the
      context of delayed PORT with importance given to TTR and PSA velocity. Category
      pT3b was consistently perceived as a poor prognosticator. The majority of
      respondents prescribe ADT for > 6 months (72%) or > 24 month (48%). CONCLUSIONS:
      Wide variation was identified among respondents in the importance given to
      pathological, clinical and biochemical parameters and in considering therapy
      duration when prescribing ADT with PORT. This demonstrates a need for consensus
      guidelines and lends support to currently accruing phase III trials designed to
      answer these questions.

PMID- 21172107
TI  - Long term prostate-specific antigen trends following subcapsular prostatectomy.
AB  - INTRODUCTION: The purpose of this study was to evaluate the utility of prostate
      specific antigen (PSA) screening for prostate cancer after subcapsular
      prostatectomy. MATERIALS AND METHODS: Data from 41 consecutive patients who
      underwent subcapsular prostatectomy at a single institution over a 15 year period
      were collected retrospectively. Patients were categorized into benign and
      malignant groups based on a diagnosis of prostate cancer identified in the
      surgical specimen or during subsequent follow up. Collected data included patient
      age, preoperative and postoperative PSA values, prostate volume determined by
      surgical specimen weight, and pathologic diagnosis. Preoperative and
      postoperative PSA velocities were calculated for patients with adequate data and
      average values were compared to determine factors that were predictive of a
      confirmed prostate cancer diagnosis. RESULTS: Thirty-one patients had adequate
      PSA values and follow up and were included in the analysis. Six (19%) were
      ultimately diagnosed with prostate cancer and 25 (81%) were never diagnosed with
      prostate cancer. Postoperative PSA velocity was found to be significantly higher
      for patients in the malignant group (1.22 +/- 1.32 ng/mL/yr) as compared to
      patients in the benign group (0.06 +/- 0.15 ng/mL/yr) (p = 0.003). CONCLUSIONS:
      After subcapsular prostatectomy, patients with prostate cancer in the surgical
      specimen or who developed prostate cancer during long term follow up had elevated
      PSA velocity compared to patients who had no evidence of cancer in the surgical
      specimen or in follow up.

PMID- 21172108
TI  - Editorial comment re: Long term prostate-specific antigen trends following
      subcapsular prostatectomy.

PMID- 21172109
TI  - Holmium laser enucleation versus transurethral resection of the prostate.
AB  - INTRODUCTION: This was a prospective, randomized clinical trial to compare the
      safety, efficacy, and medium-term durability of holmium laser enucleation of the
      prostate (HoLEP) combined with mechanical morcellation versus standard
      transurethral resection of the prostate (TURP) for the surgical treatment of
      patients with bladder outlet obstruction due to benign prostatic hyperplasia
      (BPH). The patients had prostates that were greater than 30 g and less than 100 g
      and were followed for 1 year. PATIENTS AND METHODS: From April 2008 to December
      2009, 80 consecutive patients with lower urinary tract obstruction (LUTS) due to
      BPH were randomized to either surgical treatment with HoLEP (group 1, n = 40) or
      standard TURP (group 2, n = 40). Preoperative assessments included American
      Urological Association (AUA) symptom score, serum prostate-specific antigen
      (PSA), post-voiding residual (PVR) urine volume, transrectal ultrasound (TRUS),
      and urodynamic studies. Perioperative parameters included total operating time,
      resected tissue weight, hemoglobin loss, presence or absence of blood
      transfusion, time of catheter removal, and duration of hospital stay.
      Postoperative evaluations were conducted at 1, 6, and 12 months. RESULTS:
      Patients in the HoLEP group had shorter catheterization times and hospital stays
      than patients in the TURP group. There was no significant difference in operating
      times between the two groups. Mean hemoglobin loss was lower in the HoLEP group
      (1.8 +/- 1.3 g/dL versus 2.9 +/- 1.5 g/dL). There was a significantly greater
      improvement from baseline AUA symptom scores and PVR urine volumes in the HoLEP
      group versus the TURP group, at all postoperative assessments. Postoperatively,
      25% of patients in group 1 (HoLEP) and 20% of patients in group 2 (TURP) had
      irritative voiding symptoms. Urethral stricture occurred in three cases (one case
      in the HoLEP group and two cases in the TURP group). CONCLUSION: HoLEP proved to
      be a safe and highly effective technique for surgical treatment of bladder outlet
      obstruction due to BPH.

PMID- 21172110
TI  - Application of helical tomotherapy in genitourinary malignancies.
AB  - INTRODUCTION: Helical tomotherapy (HT) is an innovative approach to the delivery
      of intensity-modulated radiation therapy which combines the imaging elements of
      helical computed tomography (CT) with megavoltage linear accelerator treatment.
      The purpose of this report is to describe our experience with the clinical
      implementation of HT for genitourinary malignancies. MATERIALS AND METHODS: All
      patients treated with a primary genitourinary malignancy were included in this
      study cohort. Descriptive statistics for various demographic and treatment
      related parameters such as patient age, primary site of disease, site of
      radiotherapy, goal of treatment, dose/fractionation, immobilization and clinical
      trial enrolment were calculated. RESULTS: A total of 57 patients diagnosed with a
      primary genitourinary malignancy were treated on the helical tomotherapy unit
      during the study period. Median age was 69 years (range 45 to 83 years) and 56
      (98.2%) patients were male. Prostate cancer was the most frequently treated
      genitourinary cancer in this cohort of 57 (94.7%) cases. Ten patients (17.5%)
      were treated with palliative intent, 46 (80.7%) with radical intent (including
      full dose prostate bed adjuvant/salvage RT), and one (1.8%) patient was treated
      in a purely adjuvant manner (high risk postop bladder). CONCLUSIONS: HT is a
      technology that can be utilized in both radical and palliative genitourinary
      treatment situations in order to deliver precise conformal IMRT therapy with
      unique localization and critical structure avoidance properties.

PMID- 21172111
TI  - Estimated volume growth characteristics of renal tumors undergoing active
      surveillance.
AB  - INTRODUCTION: The detection rate of incidental renal masses is increasing.
      Historically these masses have been treated with extirpative surgery. Hence,
      there is little information on the growth rate, metastatic potential, and natural
      history of renal tumors. Through active surveillance, we study the natural
      history of renal masses and determine their growth rate and risk for metastasis.
      MATERIALS AND METHODS: From 1997 to 2007, active surveillance was offered to
      select patients with renal masses with no evidence of metastasis. Based on
      imaging studies from the initial diagnosis to the last follow up, tumor growth
      rates were determined. RESULTS: Forty-six patients were studied for a total of 58
      masses. Mean age of patients at diagnosis was 64.3 years. Mean Charlson
      comorbidity score was 5.2 (median 5, range 2-13). Mean follow up period was 22
      months (median 17, range 5-121). Mean initial tumor volume was 6.6 cm3 (median
      2.7, range 0.03-43.2). Mean growth rate was 1.9 cm3/yr (median 0.1, range -3.8
      27.9), and 6.8% had a volume doubling time of less than 1 year. No patient
      developed radiographic evidence of metastasis or died during follow up. Thirteen
      patients (15 masses) went onto operative intervention at a mean follow up of 19
      months (median 18, range 4-36); 10/15 (67%) revealed renal cell carcinoma and
      5/15 (33%) were benign. CONCLUSIONS: In our cohort, negligible growth rates are
      observed in the vast majority of renal masses undergoing active surveillance, and
      thus, a carefully selected patient population may be safely managed with active
      surveillance with serial imaging.

PMID- 21172112
TI  - Impact of adjuvant chemotherapy on patients with lymph node metastasis at the
      time of radical cystectomy.
AB  - INTRODUCTION: Radical cystectomy (RC) remains the gold standard treatment for
      patients with muscle-invasive bladder cancer. Unfortunately, a significant
      proportion of patients will have lymph node involvement at the time of RC. We set
      out to determine the impact of adjuvant cisplatin-based chemotherapy (AC) in a
      cohort of lymph node positive patients following RC. PATIENTS AND METHODS: We
      reviewed our RC database and isolated patients with lymph node positive disease
      at the time of RC. Univariate and multivariable analysis was performed to
      identify predictors of poor outcome in patients receiving AC. Overall survival
      (OS), disease specific survival (DSS) and recurrence free survival (RFS) were
      calculated for those patients who received AC compared to those who did not.
      RESULTS: Of the 316 patients, we identified 85 patients with metastatic lymph
      node involvement at the time of RC. Fifty-five (65%) of these patients received
      AC. Median follow up was 46 months. On multivariable analysis lymph node positive
      patients receiving AC had significantly improved OS, DSS and RFS compared to
      patients who did not receive AC (p = 0.031, p = 0.028, p = 0.004). The delivery
      of AC conferred the greatest recurrence-free, disease-specific, and overall
      survival advantages to those with lymph node densities (LND) of < 20% with (p =
      0.016, p = 0.011, p = 0.007, respectively). CONCLUSION: AC administered to
      patients with known lymph node metastasis conferred a significant survival
      advantage compared to observation. Furthermore, a LND of < 20% predicts of a more
      favorable response to AC. Further studies in larger patient populations are
      warranted to reveal the exact impact of AC in this subset of patients.

PMID- 21172113
TI  - Upper pole multicystic dysplasia and ureteropelvic junction obstruction
      associated with obstructive-refluxing megaureter in a neonate with a single
      kidney.
AB  - A 20-day-old male neonate presented with fever and hydronephrosis. Evaluation
      revealed that the patient had a single left kidney and a rare combination of
      multiple congenital malformations: upper pole segmental multicystic dysplasia,
      ureteropelvic junction obstruction, and an obstructive and refluxing megaureter
      (ureterovesical junction obstruction). We performed percutaneous drainage of the
      infected and obstructed upper collecting system and then used a sequential
      approach to manage the patient's anomalies. First, we performed an upper pole
      partial nephrectomy and pyeloplasty with a modified Y ureterostomy. Second, when
      the child was older, we performed ureterovesical reimplantation with ureteral
      tailoring. Currently, after 5 years of follow up, the patient has stable renal
      function.

PMID- 21172114
TI  - 11-year survival of a renal cell cancer patient following multiple
      metastasectomy.
AB  - CASE REPORT: A renal cell cancer patient with late onset of multiorgan metastases
      showed an unusually long survival following surgical resection. Femoral
      metastasis appeared 11 years, and contra lateral kidney and adrenal gland
      metastasis 19 years after the primary nephrectomy, respectively. Following the
      resection of the femur and implantation of endoprosthesis and removal of adrenal
      gland and partial nephrectomy, the patient was disease-free 20 years after the
      first diagnosis of cancer. CONCLUSION: The long survival and successful treatment
      underline the importance and efficiency of radical metastasectomy even in the
      case of late onset multiorgan metastases of renal cell cancer. The life
      expectancies are better in the late onset of bone metastasis following the
      nephrectomy. The very late onset of metastases in this case shows however the
      importance of lifelong follow up.

PMID- 21172115
TI  - Ureteral avulsion due to lumbar disc hernia repair.
AB  - Ureteral avulsion due to lumbar disc surgery is a rare complication and to our
      knowledge, only a few cases have been reported in the literature. A 43-year-old
      woman was admitted to our clinic with right lumbar pain following spinal surgery
      for discopathy. Complete right ureteral avulsion was detected and successfully
      treated by end-to-end anastomosis of the ureter with an internal double J stent.

PMID- 21172116
TI  - Primary epithelioid hemangioendothelioma of the kidney and penis.
AB  - Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor of low malignant
      potential most commonly found in the lung, liver, and soft tissues. Here we
      describe the very rare presentations of primary EHE in the kidney and on the
      penis. One patient is a 59-year-old man with a renal lesion found incidentally on
      surveillance radiography, and the other is a 26-year-old man with an asymptomatic
      subdermal glanular lesion. Both were treated surgically via open partial
      nephrectomy and partial penectomy, respectively. Surgery is standard treatment,
      and close clinical follow up is necessary due to the unpredictable nature of EHE.

PMID- 21172117
TI  - Analysis of factors related with bleeding in percutaneous nephrolithotomy using
      balloon dilatation.
AB  - INTRODUCTION: The aim of the present study is to determine the preoperative and
      operative factors associated with bleeding in percutaneous nephrolithotomy (PNL)
      operations where tract dilatation was formed by balloon dilators. MATERIAL AND
      METHODS: A total of 378 patients underwent PNL in our department between 2003 and
      2008. After excluding missing data 310 patients were included in the study in
      whom nephrostomy tract dilatation was performed using balloon dilators. The
      amount of blood loss was estimated by calculating the change in hemoglobin (Hgb).
      Preoperative and operative factors were assessed for association with the change
      in Hgb levels. The preoperative factors were age, sex, hypertension, diabetes
      mellitus (DM), smoking, ipsilateral pyelonephritis, body mass index, serum
      creatinine level, stone localization and burden, previous ipsilateral renal stone
      surgery and extracorporeal shock wave lithotripsy and degree of hydronephrosis.
      Operative factors were operation time, calyx of puncture and tract number. The
      possible effect of surgical experience was also taken into consideration.
      Univariate and stepwise multiple linear regression analysis were performed.
      RESULTS: The average Hgb drop was 1.9 g/dL (range: 0.1 g/dL-8.8 g/dL). Ancillary
      procedures were performed due to the residual calculi in 23% of patients. The
      stone free rates increased from 77% to 94% after the secondary interventions.
      Prolonged operation time and presence of diabetes mellitus (DM) had a significant
      association with the decrease in Hgb levels (p < 0.05). However the remaining
      factors analyzed did not have any association with the change in Hgb values (p >
      0.05). Previous ipsilateral open renal stone surgery was not associated with a
      change in Hgb levels (p > 0.05). Staghorn stones and operation expertise were the
      factors related with operation time (p < 0.05). CONCLUSIONS: In patients where
      tract dilatation is gained by balloon dilators prolonged operation time and DM
      are the major risk factors related with a higher incidence of blood loss.
      Surgical expertise is highly related with operation time. It would be wise to
      operate staghorn stones when a high surgical experience is gained.

PMID- 21172118
TI  - Office based urology trials.

PMID- 21172119
TI  - Open clinical uro-oncology trials in Canada.

PMID- 21172123
TI  - Unique information about the health systems of the North.

PMID- 21172122
TI  - RNA-containing exosomes in human nasal secretions.
AB  - BACKGROUND: Exosomes are nanovesicles of endocytic origin released by cells and
      present in human body fluids such as plasma, breast milk, and bronchoalveolar
      lavage fluid. These vesicles take part in communication between cells. Recently,
      it was shown that exosomes contain both mRNA and microRNA. This RNA can be
      shuttled between cells (exosomal shuttle RNA), which is a new route of
      communication between cells. The aim of this study was to determine whether nasal
      secretions harbor exosomes and furthermore, whether these exosomes contain RNA.
      METHODS: Human nasal lavage fluid (NLF) underwent centrifugation and filtration
      to discard cells and debris, followed by a final ultracentrifugation at 120,000 *
      g to pellet the exosomes. Exosomes were detected using electron microscopy (EM),
      flow cytometry, and Western blot. RNA was extracted and analyzed using a
      Bioanalyzer. RESULTS: Exosomes were visualized as 40-80 nm, CD63(+) vesicles
      using EM. Flow cytometry of exosomes using anti-major histocompatibility complex
      class II beads revealed exosomes positive for the tetraspanins CD9, CD63, and
      CD81. Western blot confirmed the presence of exosomal protein and absence of
      proteins from the endoplasmic reticulum (ER), because the exosomes were positive
      for Tsg101, but negative for the ER marker, calnexin. Bioanalyzer analysis
      revealed that, these exosomes contain RNA. CONCLUSION: This study shows for the
      first time that NLF contains exosomes and that these exosomes contain RNA.
      Further characterization of the exosomal RNA and proteins may provide important
      information about communication in the nose and potentially provide a source of
      biomarkers for upper airway diseases.

PMID- 21172124
TI  - Organizing health care services for people living in circumpolar region is a
      tough test for national health policies.

PMID- 21172125
TI  - [Clinical analysis of 322 cases of non-epileptic cerebral palsy].
AB  - OBJECTIVE: To study the clinical features of non-epileptic seizures associated
      with cerebral palsy (CP) in children. METHODS: A total of 1 198 children with CP
      (age: 9 months to 6 years) were enrolled. The children with paroxysmal events
      were monitored by 24 hrs video-EEG (VEEG) to make sure the seizures were
      epileptic or non-epileptic. The symptoms, age, CP types and EEG features were
      observed in children with non-epileptic CP. RESULTS: Five hundred and seventy
      eight children (48.24%) presented paroxysmal events. The seizures were epileptic
      in 231 children (19.28%) and non-epileptic in 322 cases (26.88%). In the 322
      cases of non-epileptic CP, the paroxysmal events were of various kinds, including
      non-epileptic seizure tonic, seizure shake head, shrug shoulder or head
      hypsokinesis, cry or scream, panic attacks, sleep myoclonic and stereotyped
      movement. One hundred and fifty-eight (49.1%) out of the 322 children
      demonstrated nonspecific EEG abnormalities. One hundred and eleven children
      (34.5%) were misdiagnosed as epilepsy in primary hospitals. The CP children less
      than one year old showed higher frequency of non-epileptic seizures than the age
      groups over 1 year and 3 to 6 years. The frequency of non-epileptic seizures was
      the highest in children with spastic CP (168 cases, 52.2%), followed by
      dyskinetic CP (69 cases, 21.4%) and mixed type CP (65 cases, 20.2%). CONCLUSIONS:
      The paroxysmal events in children with CP partially are non-epileptic seizures
      and it is important to differentiate non-epileptic from epileptic seizures. The
      frequencies of non-epileptic seizures may be associated with a child's age and CP
      type.

PMID- 21172126
TI  - [Risk factors for ventilator-associated pneumonia in neonates and the changes of
      isolated pathogens].
AB  - OBJECTIVE: To study the risk factors for neonatal ventilator-associated pneumonia
      (VAP) and the changes of isolated pathogens in the last eight years. METHODS: The
      clinical data of 230 neonates who were admitted into the neonatal intensive care
      unit (NICU) and received mechanical ventilation for equal to or longer than 48
      hrs in 2008 were retrospectively reviewed. The isolated pathogens were compared
      with those of eight years ago. RESULTS: The incidence of VAP (25.2%) in the year
      2008 was lower than that of eight years ago (36.1%; P<0.05). The development of
      VAP was negatively correlated with the gestational age and the birth weight, but
      positively correlated with the duration of mechanical ventilation, intubation
      times, duration of hospitalization, presence of gastrointestinal bleeding and
      need for blood products transfusion. The main isolated pathogens were
      opportunistic antibiotics resistant bacteria, and the majority was gram negative
      bacilli (77%). The most frequently detected gram negative bacilli were Klebsiella
      (20%), Stenotrophomonas maltophilia (18%) and Acinetobacter (13%). Streptococcus
      mitis was the most frequently detected gram positive bacilli (14%). The
      distribution pattern of pathogens isolated in the same NICU eight years ago was
      somewhat different: Klebsiella (23%), Pseudomonas aeruginosa (17%), Acinetobacter
      (16%), Streptococcus mitis (11%), Fungi (1%) and Candida albicans (1%).
      CONCLUSIONS: The incidence of VAP is correlated with gestational age, birth
      weight, duration of mechanical ventilation and hospitalization, intubation times,
      presence of gastrointestinal bleeding and need for blood products transfusion.
      The main isolated pathogens are usually antibiotic resistant opportunistic
      bacteria. The detection rate of Stenotrophomonas maltophilia increased and that
      of Pseudomonas aeruginosa decreased when compared with eight years ago.

PMID- 21172127
TI  - [ID4 methylation patterns in childhood T line and B line lymphocytic leukemia].
AB  - OBJECTIVE: To study the relationship of methylation of inhibitor of DNA binding 4
      (ID4) gene core promoter region with childhood T line, B line and T/B acute
      lymphocytic leukemia (ALL). METHODS: Methylation-specific polymerase chain
      reaction (MS-PCR) was used to detect the methylation status of ID4 promoter
      region in 18 children with newly-diagnosed ALL (2 cases of T-ALL, 13 cases of B
      ALL and 3 cases of T/B-ALL). Thirty-four hospitalized children with non-tumor
      disease served as the control group. RESULTS: The complete methylation rate of
      ID4 gene promoter region (15/18, 83%) was significantly higher than the partial
      methylation rate (3/18, 17%) in the 18 ALL children (P<0.05). The complete
      methylation rate of ID4 gene promoter region in children with T-ALL, B-ALL and
      T/B-ALL (50%, 85% and 100% respectively) was significantly higher than that in
      the control group (18%; P<0.05). In contrast, the partial methylation rate and
      non-methylation rate in the three ALL groups were significantly lower than those
      in the control group (P<0.05). There were no statistically significant
      differences in the methylation patterns among the B-ALL, T-ALL and T/B-ALL cases.
      CONCLUSIONS: The methylation of ID4 promoter region may be related to the
      pathogenesis of childhood ALL. The methylation patterns of ID4 promoter region
      are identical in B-ALL, T-ALL and T/B-ALL.

PMID- 21172128
TI  - [Validity and reliability of the Chinese version of Pediatric Quality of Life
      Inventory Version 3.0 Asthma Modul].
AB  - OBJECTIVE: To evaluate the reliability and validity of parent proxy?report scales
      of Pediatric Quality of Life Inventory Version 3.0 (PedsQLTM) Asthma Module
      (Chinese version). METHODS: Two hundred and thirty-three asthmatic children and
      their parents from the Children's Hospital of Chongqing Medical University were
      enrolled. Health related quality of life was assessed using the above mentioned
      PedsQLTM Asthma Module. The internal consistency was assessed using Cronbach's
      alpha coefficient, while its validity was tested through correlation analysis and
      exploratory factor analysis. RESULTS: The internal consistency reliability for
      Total Scale Summary Score (Cronbach's alpha=0.86), Asthma Score (Cronbach's
      alpha=0.80), Treatment Score (Cronbach's alpha=0.78), Worry Score (Cronbach's
      alpha=0.89) and Communication Score (Cronbach's alpha=0.93) were excellent. Seven
      major factors were extracted by factor analysis which basically matched the
      designed structure of the original version accounting for nearly 66% of the
      variance. Moderate to high correlations between items and the subscales were
      found, and the correlation coefficients ranged from 0.41 to 0.92(P<0.01).
      CONCLUSIONS: The reliability and validity of the parent proxy-report scales of
      PedsQLTM 3.0 Asthma Module of the Chinese version are as good as the original
      version.

PMID- 21172129
TI  - [Mental health state of parents of children with autism].
AB  - OBJECTIVE: To study the mental health state of parents of children with autism.
      METHODS: The mental health state was evaluated by conducting the Symptom
      Checklist (SCL-90) on parents of 34 children with autism and of 35 healthy
      children. RESULTS: The SCL-90 total scores in the fathers (162.5+/-34.0) and
      mothers of autistic children (175.1+/-51.0) were significantly higher than those
      in healthy children's parents (142.4+/-42.8 and 152.3+/-40.6, respectively)
      (P<0.05). The SCL-90 scores of obsessive-compulsive symptoms, depression, anxiety
      and paranoia in the fathers of autistic children were significantly higher than
      those in the fathers of healthy children (P<0.05). The SCL-90 scores of obsessive
      compulsive symptoms, interpersonal sensitivity, depression, anxiety, paranoia,
      psychotic symptoms, hostility and sleep/diet were significantly higher in the
      mothers of autistic children than those in the mothers of healthy children
      (P<0.05). The mothers of autistic children presented higher SCL-90 factor scores
      in interpersonal sensitivity, anxiety and psychotic symptoms than the fathers
      (P<0.05). CONCLUSIONS: We should pay more attention to the mental health of
      parents of autistic children.

PMID- 21172130
TI  - [Survey on the influencing factors of malnutrition in rural children under 7
      years of age in Gansu Province].
AB  - OBJECTIVE: To study the status and influencing factors of malnutrition in rural
      children under 7 years of age in Gansu Province. METHODS: By stratified random
      cluster sampling, 9 390 rural children under 7 years of age from 4 counties of
      Gansu Province were enrolled. A cross-sectional investigation on children's
      nutritional status was performed. The major influencing factors of malnutrition
      were evaluated by logistic regression analysis. RESULTS: The detection rate of
      under-weight was 3.60% (338 cases). The growth retardation occurred in 992 cases
      (10.56%). Athrepsy was found in 196 cases (2.49%) out of 7 868 children under 5
      years of age. Gender, age, birth weight, life style, parents' educational level
      and family income were influencing factors of malnutrition. CONCLUSIONS: More
      attention should be paid to the issue of malnutrition of rural children under 7
      years of age in Gansu Province. The prevalence of malnutrition may be reduced
      through increasing family income and nutrition education, and improving parents'
      education level and children's life style.

PMID- 21172131
TI  - [Expression of imprinted genes during the course of differentiation from mouse
      embryonic stem cells to islet-like cells in vitro].
AB  - OBJECTIVE: To study the effects of in vitro inducement on the expression of SF1-G
      imprinted genes, Kcnq1 and Cdkn1c during the course of differentiation from mouse
      embryonic stem (ES) cells to islet-like cells. METHODS: Mouse ES cells were
      induced to differentiate into islet-like cells in vitro. The expression of islet
      specific markers was tested by RT-PCR or immunofluorescence. RT-PCR/RFLP was used
      to test the imprinted genes parental expression in cells at different stages.
      RESULTS: Islet specific genes, such as Insulin, Glucagon, Somatostatin, IAPP and
      Glut2, were expressed in differentiated cells. The proteins of insulin, C-peptide
      and Somastatin were expressed in the final stage cells. Imprinted gene Kcnq1 and
      Cdkn1c were biallelicly expressed in islet-like cells. CONCLUSIONS: Mouse ES
      cells can be successfully induced into islet-like cells in vitro. Gene imprinting
      status of Kcnq1 and Cdkn1c may be changed in differentiated cells (causing loss
      of imprinting) during the in vitro inducement.

PMID- 21172132
TI  - [Efficacy of microencapsulated HepG2 cells transplantation in rats with
      hepatolenticular degeneration].
AB  - OBJECTIVE: To evaluate the efficacy of intraperitoneal transplantation of
      microencapsulated HepG2 cells in rats with hepatolenticular degeneration (HLD).
      METHODS: HLD was induced by copper-overloaded diet with forage containing 1 g/kg
      copper sulfate and water with 0.185% copper sulfate for 12 weeks in rats. One
      hundred and twenty three-month-old male Wistar rats were randomly intraperitoneal
      injected with normal saline (NS), microencapsulated HepG2 cells or non
      microencapsulated HepG2 cells 9 weeks after copper-overloaded diet. Blood or
      liver samples were obtained at five time points: 3, 7, 14, 21 and 28 days after
      transplantation (n=8). The other 8 rats receiving normal diet were used as the
      control group. Serum levels of ALT, AST, albumin and Cu and liver Cu contents
      were measured. RESULTS: Serum ALT, AST and Cu levels and liver Cu contents in the
      NS-treated HLD, microencapsulated HepG2 cells and non-microencapsulated HepG2
      cells transplantation groups increased significantly at all time points, in
      contrast, serum albumin levels decreased significantly in the NS-treated HLD and
      non-microencapsulated HepG2 cells transplantation groups compared with those in
      the control group at all time points (P<0.05), but serum albumin levels in the
      microencapsulated HepG2 cells transplantation restored to the level of the
      control group 28 days after transplantation. Serum ALT, AST and Cu levels and
      liver Cu contents in the microencapsulated HepG2 cells and non-microencapsulated
      HepG2 cells transplantation groups were significantly lower, in contrast, albumin
      levels were higher than those in the NS-treated HLD group on almost time points
      (P<0.05). Serum levels of ALT, AST and Cu and liver Cu contents in the
      microencapsulated HepG2 cells transplantation group decreased 7 or 14 days after
      transplantation, while serum albumin levels increased significantly 14 days after
      transplantation compared with those in the non-microencapsulated HepG2 cells
      transplantation group (P<0.05). CONCLUSIONS: Intraperitoneal transplantation of
      microencapsulated HepG2 cells can relieve hepatic damage, reduce serum and liver
      Cu levels, and improve copper metabolism, therefore it is promising for the
      treatment of HLD.

PMID- 21172133
TI  - [Effect of rhIGF-1 on cytochrome C and caspase-3 expression in neonatal rats with
      hypoxic-ischemic brain damage in vivo].
AB  - OBJECTIVE: To study the effect of rhIGF-1on the mRNA and protein expression of
      cytochrome C (Cyt-C) and caspase-3 in neonatal rats with hypoxic-ischemic brain
      damage (HIBD). METHODS: Ninety neonatal Sprague-Dawley rats were randomly divided
      into three groups: normal control, HIBD, and HIBD+rhIGF-1 (rhIGF-1 was given
      intraperitoneally right after HI). Rat HIBD model was prepared according the Rice
      Vannucci method. RT-PCR and Western blot methods were used to measure the mRNA
      and protein expression of Cyt-C and caspase-3 24, 48 and 72 hrs after HI (n=10
      each time point). RESULTS: At all time points, both Cyt-C mRNA and caspase-3 mRNA
      expression levels in the HIBD group increased compared with those in the normal
      control group, and those in the HIBD+rhIGF-1 group also increased compared with
      that in the normal control group but decreased compared with that in the HIBD
      group. There were statistical significances among the three groups (P<0.01). At
      all time points, the changes of both Cyt-C and caspase-3 protein expression in
      the three groups were similar to those of the mRNA expression: both Cyt-C and
      caspase-3 protein expression levels increased in the HIBD group compared with
      those in the normal control group, and those in the HIBD+rhIGF-1 group also
      increased compared with those in the normal control group but decreased compared
      with those in the HIBD group. There were statistical significances among the
      three groups (P<0.01).Pearson correlation analysis showed that mRNA and protein
      expression of Cyt-C were positively correlated to casapse-3 mRNA and protein
      expression in the HIBD and the HIBD+rhIGF-1 groups. CONCLUSIONS: rhIGF-1 may
      inhibit the Cyt-C release and caspase-3 expression, and thus provides
      neuroprotection against HIBD in neonatal rats.

PMID- 21172134
TI  - [Effects of glutamine on platelet-derived growth factor and its receptor
      following septic brain damage in rats].
AB  - OBJECTIVE: This study investigated the expression of platelet-derived growth
      factor-B (PDGF-B) and its receptor-beta (PDGFR-beta) in rat cerebral cortex
      following sepsis and explored the possible underlying mechanism of neuro
      protective effect of glutamine (Gln). METHODS: One hundred and twenty 10-day-old
      Wistar rats were randomly divided into three groups: a control group that
      received an intraperitoneal injection of normal saline (1 mL/kg), a sepsis group
      that received an intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg),
      and a Gln treatment group that was administered with Gln (1.346 g/kg) 1 hr before
      LPS injection. The rats were subdivided into 5 groups sacrificed at 2, 6, 12, 24
      and 72 hrs after LPS or normal saline injection (n=8). The distribution and
      expression of PDGF-B and PDGFR-beta in the cerebral cortex were ascertained by
      immunohistochemistry and Western blot. RESULTS: The immunohistochemistry results
      showed that the PDGF-B and PDGFR-beta expression in the cerebral cortex increased
      significantly in the Gln treatment group 72 hrs after LPS injection compared with
      that in the control and the sepsis groups. The Western blot results showed that
      the PDGF-B expression in the brain tissue in the sepsis and the Gln treatment
      groups were significantly lower than that in the control group 2, 6, and 12 hrs
      after LPS injection, while the Gln treatment group had increased PDGF-B
      expression compared with the sepsis group 12 and 72 hrs after LPS injection.
      Compared with the control group, the PDGFR-beta expression in the brain tissue in
      the sepsis group increased 2 and 6 hrs after LPS injection but decreased
      significantly 72 hrs after LPS injection. There were no significant differences
      in the PDGFR-beta expression between the Gln treatment and the control groups at
      all different time points. CONCLUSIONS: Gln can increase the PDGF-B and PDGFR
      beta expression in the brain tissue of rats with sepsis. The increased PDGF-B and
      PDGFR-beta expression might contribute to neuro-protective effects of Gln.

PMID- 21172135
TI  - [Expression of insulin receptor substrates in pancreas of rats with intrauterine
      growth retardation].
AB  - OBJECTIVE: To study the expression of insulin receptor substrate-1(IRS-1) and
      insulin receptor substrate-2 (IRS-2) in pancreas of rats with intrauterine growth
      retardation (IUGR). METHODS: An IUGR rat model was prepared by protein
      malnutrition during pregnancy. The pancreas samples of the IUGR pups were
      obtained at birth, and 3 weeks and 8 weeks of age. The expression of IRS-1 and
      IRS-2 mRNA were ascertained by RT-PCR. Western blot was used to measure the
      protein expression of IRS-1 and IRS-2. The rat pups born from the mother rats who
      received normal diet during pregnancy severed as the control group. RESULTS: The
      expression levels of IRS-2 mRNA and protein in pancreas of the IUGR group were
      significantly lower than those in the control group at all three time points
      (P<0.05). There were no significant differences in the expression levels of IRS-1
      mRNA and protein in pancreas between the IUGR and the control groups.
      CONCLUSIONS: The IRS-2 expression levels in pancreas in IUGR rats decrease
      significantly at birth, and 3 weeks and 8 weeks of age. This might be one of the
      molecular mechanisms for the development of metabolic syndrome in later life in
      IUGR individuals.

PMID- 21172136
TI  - [Effects of vitamin A on the immune function of intestinal mucosa lymphocytes in
      mice].
AB  - OBJECTIVE: To study the effects of vitamin A on the development of T lymphocytes
      in peripheral blood and small intestine and on the cytokine response of
      intestinal mucosa in mice. METHODS: Twenty young mice were randomly fed with
      forage containing vitamin A 250 or 4 IU/g (n=10 each). Three weeks later, the
      levels of CD4+ CD25+ T subsets in peripheral blood and intestinal mucosa were
      measured by flow cytometry. The levels of cytokines IFN-gamma, IL-4, IL-17 and IL
      23 in stool were measured using ELISA. RESULTS: The levels of CD4+ CD25+ T
      subsets in peripheral blood and intestinal mucosa in the 250 IU/g vitamin A group
      were significantly higher than those in the 4 IU/g vitamin A group (P<0.05). The
      IL-4 level in stool increased, in contrast, the IL-23 level in stool decreased
      significantly in the 250 IU/g vitamin A group when compared with the 4 IU/g
      vitamin A group (P<0.05). CONCLUSIONS: vitamin A may promote the development of
      CD4+ CD25+ T lymphocytes in peripheral blood and small intestine. Moreover, it
      may be involved in intestinal mucosa-associated immune response by regulating
      cytokines IL-4 and IL-23.

PMID- 21172137
TI  - [Cell proliferation and signal pathway after knockdown and RESC concurrent rescue
      of RNAi lentiviral vector on human PTEN gene in T-lymphocytes].
AB  - OBJECTIVE: To construct the lentiviral expression vectors of human PTEN gene for
      RNA interference (RNAi) and concurrent rescue of RNAi escape strategy construct
      (RESC) and to observe the changes of signal pathway, cell proliferation and cell
      cycle after PTEN gene knockdown and RESC concurrent rescue in human T
      lymphocytes, in order to provide an experimental basis for a further research
      into the pathogenesis of acute lymphoblastic leukemia in children. METHODS: Using
      lentiviral vector systems to construct lentiviral vectors of human PTEN gene for
      RNAi and its RESC concurrent rescue, human T-lymphocytes were transfected with
      the lentiviruses. The cell models were established with PTEN gene knockdown (T-LC
      shPTEN) and RESC concurrent rescue (T-LC-rrshPTEN). After knockdown and RESC
      concurrent rescue of PTEN gene, the expression of PTEN protein and the activation
      of AKT signal pathway, cell proliferation and cell cycle were detected by Western
      blot, MTT assay and flow cytometry respectively. RESULTS: The RNAi-mediated
      lentiviruses can down-regulate the expression of the human PTEN gene effectively.
      After the down-regulation of PTEN gene, the T-lymphocytes grew faster. The phase
      G0/G1 cells decreased and the phases S and G2/M cells increased significantly.
      The PI3K/AKT signal pathway was activated. All RNAi phenomenon caused by PTEN
      gene knockdown were recovered fully by RESC concurrent rescue of RNAi.
      CONCLUSIONS: The lentiviral expression vectors of human PTEN gene for RNAi and
      RESC concurrent rescue of RNAi are constructed successfully. The PI3K/AKT signal
      pathway can be activated and the proliferation of human T-lymphocytes can be
      promoted after PTEN gene knockdown.

PMID- 21172138
TI  - [A comparative study on three models of co-culture of neurons and astrocytes].
AB  - OBJECTIVE: To find a better method for harvesting highly purified neurons by
      comparing three methods used for co-culture of neurons and astrocytes. METHODS:
      The co-culture models of neurons and astrocytes were established by primary
      culture, Banker's co-culture method or Transwell cell-culture inserts. The
      neurons and astrocytes cultured in vitro were from neonatal rats. RESULTS: The
      highly purified neurons were not harvested by primary culture because the neurons
      and astrocytes grew on the same cover slip and it was difficult to control the
      growth velocity of astrocytes. The highly purified neurons were harvested by
      Banker's co-culture method or the method using Transwell cell-culture inserts,
      but the procedure of the former was more complicated than that of the later.
      CONCLUSIONS: The culture method using Transwell cell-culture inserts is
      recommended for the establishment of the co-culture system of neurons and
      astrocytes.

PMID- 21172139
TI  - [Comparison of the efficacy of 10-day sequential therapy and conventional triple
      therapy for Helicobacter pylori eradication in children].

PMID- 21172140
TI  - [Effect of intravenous immunoglobulin on neutrophil counts in children with
      Kawasaki disease].

PMID- 21172141
TI  - [Treatment outcome of cyclic vomiting syndrome in children].

PMID- 21172142
TI  - [A follow up study on long-term relapse in children with neuroblastoma].

PMID- 21172143
TI  - [Clinical diagnosis and treatment of bronchiolitis obliterans in children].

PMID- 21172144
TI  - [Plasma hydrogen sulfide levels in children with severe pneumonia].

PMID- 21172145
TI  - [Pleural effusion caused by peripherally inserted central catheter: report of 2
      cases].

PMID- 21172146
TI  - [A case report of Alagille syndrome].

PMID- 21172147
TI  - [Relationship between telomere/telomerase and the developmental origins of
      metabolic syndrome].

PMID- 21172148
TI  - [Influence of antisense VEGF oligodeoxynucleotides formulated in cationic
      liposome on microvessel density and VEGF expression of lung cancer].
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is known to be one of the
      most important factors for angiogenesis and tumor cell infiltration. The aim of
      this study is to determine the influence of phosphorothioate-moeified antisense
      VEGF oligodeoxynucleotides (ASODN) formulated in cationic liposome on microvessel
      density (MVD) and VEGF expression of lung cancer. METHODS: Lewis lung carcin- oma
      model was established by subcutaneous injection of Lewis lung carcinoma cells
      into 40 C57BL/6 mice. Within 24h after inoculation, mice were randomly assigned
      to four groups treated with ASODN, sense oligodeoxynucleotides (SODN), mismatch
      oligodeoxynucleotides (MODN), or liposome alone respectively, twice a week for 4
      weeks. The weight and volume of subcutaneous tumors were measured. The
      morphological and ultrastructural changes of tumor cells were observed under
      microscope and electron microscope. MVD and expression of VEGF protein and VEGF
      mRNA were detected by immunohistochemical staining and RT-PCR. RESULTS: The tumor
      weight in the control group was (7.83+/-0.78)g, and (4.49+/-0.43)g in the ASODN
      group (P < 0.01). The inhibition rate of tumor growth in the ASODN, SODN and MODN
      groups was 42.6%, 5.1% and 3.2% respectively. MVD and expression of VEGF protein
      and VEGF mRNA were decreased markedly in the ASODN group compared to the other
      three groups (P < 0.01). CONCLUSIONS: The results demonstrate that MVD and VEGF
      expression of lung cancer can be inhibited by VEGF ASODN injected into tumor
      tissue in C57BL/6 mice.

PMID- 21172149
TI  - [Effects of Gax gene transfection on proliferation and expression of proto
      oncogenes in A549 cells].
AB  - BACKGROUND: Lung cancer is the leading cancer of malignant tumor in China.It is
      the direction that poeple make efforts to seek gene therapy of lung cancer. The
      aim of this study is to explore the effects of transfected growth arrest-specific
      homeobox gene (Gax gene) on the proliferation and expressions of c-fos and c-jun
      mRNA in A549 cells. METHODS: A549 cells were transfected with Gax gene by
      adenovirus. Expressions of Gax mRNA and protein were detected by RT-PCR and
      immunocytochemistry. The expressions of c-fos and c-jun mRNA were evaluated by RT
      PCR. The proliferation inhibition effect of Gax transfection on A549 cells was
      evaluated by MTT assay. RESULTS: Only in the A549 cells transfected with Gax gene
      the Gax expression was confirmed by RT-PCR and immunocytochemistry. Compared with
      that in the control group, c-fos and c-jun mRNA level decreased significantly in
      Gax-transfected A549 cells (t=7.755, P < 0.01; t= 5.938 , P < 0.01). MTT assay
      showed that the proliferation inhibition rates of A549 cells transfected by Ad
      Gax for 24h, 48h and 72h were (47.35+/-5.36)%, (54.96+/-1.78)%, and (65.39+/
      5.11)% respectively. And these proliferation inhibition rates were significantly
      higher than those in the control group (Chi-Square=7.152, 9.431 and 12.847, P <
      0.01). CONCLUSIONS: Gax gene can inhibit the proliferation of A549 cells. Its
      molecular mechanism may be through down-regulating the expressions of c-fos and c
      jun.

PMID- 21172150
TI  - [Effects of anti-MDM2 siRNA on radiation-mediated cell killing in lung cancer
      cell line A549].
AB  - BACKGROUND: Lung cancer cell lines A549 and NCI-H446 with different
      radiosensitivity to ionizing radiation (IR) have different MDM2 gene expression
      status, which may contribute to the radioresistance of cells. The aim of this
      study is to use small interfering RNA (siRNA) targeting MDM2 to investigate the
      influence of MDM2 gene silencing on radioresponse of A549 cell. METHODS: Plasmid
      targeting MDM2 was constructed with pPUR/U6 vector and oligonucleotide designed
      according to the sequence of effective antisense oligonucleotides and principles
      of siRNA design. A549 cells were transfected by LipofectamineTM 2000. MDM2
      expression in A549 cells was detected by RT-PCR and Western blot. Radiation
      mediated cell killing was detected by flow cytometry. RESULTS: Two out of three
      siRNA plasmids were constructed successfully. siRNA transfection resulted in
      downregulaton of MDM2 expression of A549 cells on mRNA and protein levels. After
      treated with siRNA, radiation-mediated cell killing of A549 cells was
      significantly increased (P < 0.01). CONCLUSIONS: The results support the
      hypothesis that MDM2 gene is a candidate for radioresistance in A549 cells. siRNA
      targeting to MDM2 can enhance the radiation-mediated cell killing of A549 cells.

PMID- 21172151
TI  - [Detection of metabolites of tobacco-specific nitrosamine 4-(methylnitrosamino)-1
      (3-pyridyl)-1-butanone in lung cancer smokers' urine].
AB  - BACKGROUND: It was reported that tobacco-specific nitrosamine 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was a powerful pulmonary
      carcinogen, predominantly inducing adenocarcinoma of the lung in mouse. The aim
      of this study is to assay metabolites of NNK, which are 4-(methylnitrosamino)-1
      (3-pyridyl)-1-butanol (NNAL) and its O-glucuronide (NNAL-Gluc), and their ratio
      (NNAL-Gluc/NNAL) in smokers and non-smokers' urine, and to explore the
      carcinogenicity of NNK among different people. METHODS: Using high pressure
      liquid chromatograph (HPLC) and gas chromatograph-mass tadom (GC-MS/MS), NNAL
      Gluc and NNAL in 24h urine were detected in 8 healthy smokers, 10 lung cancer
      smokers and 4 healthy non-smokers. RESULTS: Both of the two metabolites were not
      found in non-smokers' urine. The ratios of urine NNAL-Gluc/NNAL were greatly
      different among different smokers. The mean ratio of NNAL-Gluc/NNAL in healthy
      smokers was 4.95, and 0.5 in lung cancer smokers. CONCLUSIONS: The results
      provide the first evidence for metabolite detection of tobacco-specific
      nitrosamine in Chinese smokers' urine . The result suggests that detoxification
      ability of healthy smokers is higher than that of lung cancer smokers. It may
      provide a detective way to screen high risk people for lung cancer in smokers.

PMID- 21172152
TI  - [Inhibitory effects of shRNA targeting layilin on adhesion and invasion behavior
      of human lung adenocarcinoma A549 cells induced by hyaluronan in vitro].
AB  - BACKGROUND: It has been proved that hyaluronan was involved in adhesion and
      invasion behavior of varied tumor cells. Layilin is a receptor of hyaluronan
      found recently and has close relationship with cytoskeleton. The aim of this
      study is to investigate the effect of short hairpin RNA (shRNA) targeting layilin
      on adhesion and invasion behavior of human lung adenocarcinoma cell line A549
      induced by hyaluronan in vitro. METHODS: RNA interference plasmid that included
      U6 promoter and could express shRNA targeting layilin was designed, constructed,
      and transfected into A549 cell line. Layilin expression was examined by RT-PCR,
      Western blot and immunofluorescence. Adhesive and invasive ability was examined
      by plate adhesion model and Boyden chamber model. RESULTS: After plasmid
      transfected, layilin expression in A549 cells obviously decreased (P < 0.01), and
      the numbers of adhesive A549 cells on plate and A549 cells permeating septum of
      Boyden chamber induced by hyaluronan also significantly decreased (P < 0.01).
      CONCLUSIONS: The shRNA targeting layilin can efficiently inhibit the adhesive and
      invasive ability of A549 cells induced by hyaluronan in vitro.

PMID- 21172153
TI  - [Abnormal promoter methylation of p14(ARF), p16(INK4a)and BUB3 genes in malignant
      transformed cells induced by radiation].
AB  - BACKGROUND: The methylation of tumor suppressor genes is believed to be one of
      the most important mechanisms of oncogenesis. In order to research the malignant
      transformed mechanism induced by radiation, the abnormal promoter methylation of
      p14(ARF) , p16(INK4a) and BUB3 genes are detected in the transformed human
      bronchial epithelial cells (BEP2D) induced by alpha-particles. METHODS: Abnormal
      promoter methylations were detected with methylation specific PCR (MSP). The
      level of p14 ARF gene transcription was analyzed by using RT-PCR. DNA was
      purified and transformed and sequenced. RESULTS: p14(ARF) gene was not methylated
      in BEP2D cells, but was methylated in the malignant transformed BERP35T-1 cells,
      and the level of its transcription was depressed remarkably in the latter.
      However p16(INK4a) gene, which shares two exons with p14 (ARF) gene, was not
      methylated. BUB3 gene was not methylated in BEP2D as well as BERP35T-1 cells and
      this was further proved by sequencing analysis. CONCLUSIONS: The methylation of
      two tumor suppressor genes (p14(ARF) and p16(INK4a)) that share two exons and
      controll cell cycle are not synchronous in the transformed human bronchial
      epithelial cells induced by alpha-particles, and the methylated one (p14(ARF)) is
      repressed in transcription. The gene of mitosis spindle check-point (BUB3) is
      unmethylated.

PMID- 21172154
TI  - [Expression of canstatin gene in human lymphocytes and its inhibitory effect on
      growth and metastasis of Lewis lung carcinoma].
AB  - BACKGROUND: In recent years, many progresses have been made in molecular target
      therapy for lung cancer, in which anti-angiogenic target therapy is a hot spot
      drawing researchers' attention. The aim of this study is to explore the
      expression of canstatin gene transfected into human lymphocytes and its
      inhibitory effect on growth and metastasis of Lewis lung carcinoma. METHODS: The
      eukaryotic expression vector of pCMV-Script and the recombinant pCMV
      Script/Canstatin vector were separately transfected into lymphocytes by
      electroporation. The expression of canstatin protein in supernatant of
      lymphocyues was examined by SDS-PAGE assay. Furthermore, Lewis lung carcinoma
      cells were subcutaneously inoculated to C57BL mice to make animal model of tumor.
      When the transplanted tumors on the mice developed to 1cm3, the 30 mice were
      randomized into 3 groups, which were injected with 0.2mL supernatant of
      lymphocytes transfected with recombinant vector or naked vector, or 0.2mL NS
      respectively. After the treatment for 14 days, the size and pathological section
      of subcutaneous tumors were observed, and the number of pulmonary metastatic node
      was calculated. RESULTS: Canstatin protein was found in supernatant of the
      lymphocytes in the recombinant vector group by SDS-PAGE assay. After the
      treatment, the tumor size in the recombinant vector group (1.49cm3+/-0.18cm3) was
      significantly smaller than that in the naked vector group (2.44cm3+/- 0.19cm3)
      and NS group (2.53cm3+/-0.18cm3) (P=0.000). The numbers of pulmonary metastatic
      node were 3.40+/-1.14, 7.60+/-2.61 and 7.60+/-2.41 in the recombinant vector
      group, naked vector group and NS group respectively (recombinant vector group vs
      the other two groups, P=0.013). CONCLUSIONS: The pCMV-Script/Canstatin vector can
      express canstatin protein in human lymphocytes. Canstatin has strongly inhibitory
      effect on growth and metastasis of mouse Lewis lung carcinoma.

PMID- 21172155
TI  - [Growth characteristics of A549 lung adenocarcinoma multicellular spheroid].
AB  - BACKGROUND: Owing to the limitation of monolayer tumour cells or transplanted
      tumor in radiation biology, multicellular spheroid (MTS) as a model of entity
      tumor had a wide range of application. This research aims to study the growth
      characteristics of A549 lung adenocarcinoma MTS so as to choose the best ones to
      perform experiments. METHODS: 1.75*107 A549 cells in 35mL were transfered into
      the 100mm incubator sealed with 2% agarose to have a rotating culture with
      60r/min. After 40 hours every MTS was transfered into each of the 96 wells of
      multi-well plates coated with 2% agarose to have a static culture. RESULTS:
      During the rotation stage the MTS was round, the size was uniform, and the
      conjunction between cells was loose. After about 10 days of static culture, when
      the diameter of MTS at 429 to 570 MUm the conjunction was close. After 26.5 days
      of static culture, the diameter of MTS became 1358.5 MUm which could not be used
      for experiment. Observed under electron microscopy the cells in the MTS grew well
      without any apoptosis and necrosis. The cell cycle of MTS was dominated by G0 and
      G1 stage. CONCLUSIONS: Combination of rotating and static culture is a simple
      method to produce MTS which has similar growth characteristics with entity tumor
      and is best suitable for experiment research when the diameter is about 500 MUm.

PMID- 21172156
TI  - [A randomized, prospective, multi-centre clinical trial of NP regimen
      (vinorelbine+cisplatin) plus Gensing Rg3 in the treatment of advanced non-small
      cell lung cancer patients].
AB  - BACKGROUND: Gensing Rg3 is an active component from ginseng. The aim of this
      study is to observe the clinical anticancer effect of Rg3 in combination with
      chemotherapy regimen NP (vinorelbine+cisplatin) in advanced non-small cell lung
      cancer (NSCLC). METHODS: Stage III-IV NSCLC patients confirmed by pathology or
      cytology all received vinorelbine plus cisplatin for at least two cycles, and
      were randomized into two groups: patients in arm A also received placebo twice a
      day, while patients in arm B received two tablets of Rg3 twice a day for at least
      two months. The endpoints of the study were the efficacy, survival and tolerance
      of patients. RESULTS: From July 2000 to May 2002, 115 patients were enrolled into
      the trial. The patients' characteristics were well balanced in the two groups.
      Sex of patients: male, 79; female 36. Types of pathology: adenocarcinoma, 71;
      squamous cell carcinoma, 29; adenosquamous carcinoma, 8; others, 7. TNM stage:
      stage III, 45; stage IV, 70. Prior chemotherapy: with, 17; without, 98. Prior
      radiotherapy: with, 15; without, 100. Prior surgical treatment: with, 23;
      without, 92. Nine patients discontinued from the trial due to severe adverse
      effects (5) and other reasons (4), so there were 106 patients evaluable for
      clinical efficacy. The response rate was 14.5% (8/55) in arm A, and 33.3% (17/51)
      in arm B (P=0.011). The survival time in arm A was 9.7 months (mean) and 8.0
      months (median), and 15.3 months (mean) and 10.0 months (median) in arm B
      (P=0.0088). CONCLUSIONS: Preliminary results show improvements in response rate
      and survival time (median and mean) in Rg3 arm compared with placebo arm. It is
      worthy to confirm the results in further clinical trials.

PMID- 21172157
TI  - [Expression of STK15 and its significance in squamous cell carcinoma and
      adenocarcinoma of the lung].
AB  - BACKGROUND: Serine threonine kinase 15 (STK15) is a kind of mitotic kinase. The
      overexpression of STK15 is significantly associated with carcinogenesis in many
      tumors, however, its expression and significance in human lung cancer are still
      unclear. The aim of this study is to investigate the expression of STK15 in
      squamous cell carcinoma and adenocarcinoma of the lung and to analyze the
      correlation between STK15 expression and clinicopathological factors. METHODS:
      The pattern of STK15 protein expression was detected in 44 squamous cell
      carcinomas, 36 adenocarcinomas and 20 paracancerous lung tissue samples by
      immunohistochemistry method using anti-STK15 antibody. The relative quantity of
      STK15 protein expression was detected by Western blot, and STK15 mRNA expression
      was detected by RT-PCR in 40 fresh lung cancer samples and corresponding
      paracancerous lung tissues. RESULTS: Positive expression rate of STK15 protein
      was 68.75% (55/80) in lung cancer tissues and 0% in paracancerous controls (P <
      0.001). STK15 expression was significantly related to differentiation grade of
      lung cancer (P=0.011), but not to histological classification, TNM stages or
      lymphatic metastasis (P > 0.05). The relative expression levels of STK15 protein
      (P < 0.001 ) and STK15 mRNA (P < 0.001) in lung cancer tissues were both
      significantly higher than those of corresponding paracancerous lung tissues.
      CONCLUSIONS: The expression of STK15 protein and STK15 mRNA is significantly
      higher in lung cancer tissues than that in paracancerous lung tissues. The
      expression of STK15 correlates with differentiation of lung cancer.

PMID- 21172158
TI  - [Expression of DeltaNp73 in human NSCLC and clinical implication].
AB  - BACKGROUND: DeltaNp73 is an isoform of the p53 homologue p73, which lacks an NH2
      terminal transactivation domain and antagonizes the induction of gene expression
      by p53 and p73. The aim of this study is to investigate the expression of
      DeltaNp73 mRNA in non-small cell lung cancer (NSCLC) and to analyse its relations
      with clinicopathologic factors and prognosis. METHODS: Semiquantitative reverse
      transcriptase polymerase chain reaction (RT-PCR) was used to detect the
      expression of DeltaNp73 mRNA in 40 resected NSCLC specimens with the neighboring
      noncancerous tissue. The significance of DeltaNp73 mRNA expression was analyzed
      statistically. RESULTS: DeltaNp73 mRNA was highly expressed in lung cancer
      tissues (62.7%, 32/51) while negative in neighboring noncancerous tissue. The
      expression of DeltaNp73 mRNA was associated with pathological TNM stage
      (P=0.046), but not associated with age, gender, histological type and
      differentiation status. Survival of patients with high DeltaNp73 mRNA was
      significantly poorer than those with low DeltaNp73 mRNA levels (P < 0.001).
      Multivariate analysis revealed that DeltaNp73 mRNA levels were a significant
      prognostic factor, independent of the other conventional prognostic factors.
      CONCLUSIONS: NSCLC has overexpression of DeltaNp73 mRNA, which is closely related
      to TNM stages and prognosis of patients with NSCLC. These results suggest that
      measurement of DeltaNp73 mRNA levels in tumor tissues might be useful as a
      promising predictor for the prognosis of patients with NSCLC.

PMID- 21172159
TI  - [Relationship between tumor size and lymph node metastasis in squamous cell
      carcinoma and adenocarcinoma of the lung].
AB  - BACKGROUND: Lymphatic dissemination is the main approach of metastasis in lung
      cancer, and it is also an important prognostic factor. The aim of this study is
      to explore the relationship between tumor size and lymph node metastasis in
      squamous cell carcinoma and adenocarcinoma of the lung. METHODS: A total of 240
      patients diagnosed as squamous cell carcinoma and adenocarcinoma were studied.
      The relationship between tumor size and lymph node metastasis was analyzed.
      RESULTS: Lymph node metastasis rate in maximum diameter (d)<=2cm, 2cm < d<=3cm,
      3cm < d<=6cm, 6cm < d<=10cm, and d > 10cm groups was 50.0%, 35.1%, 52.8%, 52.1%
      and 71.4%, respectively. There was no correlation between tumor size and lymph
      node metastasis (r=0.10, P > 0.05). Lymph node metastasis occurred more
      frequently in adenocarcinoma (58.8%) than that in squamous cell carcinoma (42.9%)
      (P < 0.05). Mediastinal lymph node metastasis was found in 7 patients (16.3%)
      with d<=3cm, who were all diagnosed as moderate or poor differentiation.
      CONCLUSIONS: Lymph node metastasis is not related to tumor size. Lymph node
      metastasis occurs more frequently in adenocarcinoma than it does in squamous cell
      carcinoma. Mediastinal lymph node metastasis can be found in tumor with d<=3cm,
      and differentiation grade may play an important role in lymph node metastasis.

PMID- 21172160
TI  - [Tracheo-carinal reconstruction, bronchoplasty and vascular reconstruction in the
      treatment of central lung cancer].
AB  - BACKGROUND: To maximize the preservation of functional pulmonary parenchyma,
      extend the indication of lung cancer operation and improve the life quality of
      patients with central lung cancer, reconstruction of carina, bronchoplasty and
      arterioplasty are widely used with good efficacy. The aim of this study is to
      summarize the clinical results of reconstruction of carina, bronchoplasty and
      arterioplasty in the treatment of 79 patients with central lung cancer. METHODS:
      From June, 1988 to June, 2005, reconstruction of carina, bronchoplasty and
      arterioplasty were carried out in 79 patients with central lung cancer. The ope-
      rations included single sleeve lobectomy in 58 cases, double sleeve lobectomy in
      15 cases, carinal resection and reconstruction in 6 cases. RESULTS: There was no
      operative death in this series. Seven patients had operative complications and
      the operative complication rate was 8.86% (7/79). The 1-, 3-, 5- and 10-year
      survival rates were 78.5%, 59.5%, 35.4% and 17.7% respectively. CONCLUSIONS:
      Reconstruction of carina, bronchoplasty and arterioplasty can significantly
      protect pulmonary function, improve the prognosis and increase the curative rate
      and long term survival in patients with central lung cancer.

PMID- 21172161
TI  - [Study on the value of tumor markers ProGRP, CYFRA21-1, NSE and CEA in the
      differential diagnosis of pleural effusion].
AB  - BACKGROUND: Malignant pleural effusion is usually caused by lung cancer, and
      tumor markers may be helpful to its differential diagnosis. The aim of this study
      is to explore the clinical value of serum and pleural effusion pro-gastrin
      releasing peptide (ProGRP), neuron specific enolase (NSE), cyto- keratin fragment
      19 (CYFRA21-1) and carcinoembryonic antigen (CEA) in differential diagnosis and
      histological typing of malignant pleural effusion caused by lung cancer. METHODS:
      According to histological type of primary tumor, 99 patients with malignant
      pleural effusion caused by lung cancer were divided into small cell lung cancer
      (SCLC) group, adenocarcinoma group and squamous cell carcinoma group, with 37
      patients with benign pleural effusion and 35 healthy persons as controls.
      Diagnostic value of serum and pleural effusion ProGRP , NSE, CYFRA21-1 and CEA
      was evaluated for each group. RESULTS: The levels of ProGRP, NSE, CYFRA21-1 and
      CEA in serum and pleural effusion of all the malignant groups were significantly
      higher than those in the control groups (P < 0.01). In the SCLC group, detection
      of pleural effusion ProGRP showed the highest Youden index and accuracy. In the
      adenocarcinoma group and squamous cell carcinoma group, combined detection of
      pleural effusion CEA+CYFRA21-1 (on parallel test) showed the highest Youden index
      and accuracy. CONCLUSIONS: Detection of pleural effusion tumor markers ProGRP,
      CYFRA21-1, NSE and CEA is of great clinical value in differential diagnosis and
      histological typing of malignant pleural effusion. Pleural effusion ProGRP is the
      optimal tumor marker for malignant pleural effusion caused by SCLC. Pleural
      effusion CEA+CYFRA21-1 (on parallel test) is a good auxiliary diagnosis index for
      malignant pleural effusion caused by adenocarcinoma and squamous cell carcinoma
      of the lung.

PMID- 21172162
TI  - [Preliminary result on pediculoplasty for treatment of vertebral pedicular
      osteolytic metastasis of lung cancer].
AB  - BACKGROUND: Vertebral pedicular metastasis in lung cancer patients are common.
      This is a preliminary study on methods and clinical application of percutaneous
      pediculoplasty in the treatment of vertebral pedicular osteolytic metastasis of
      lung cancer. METHODS: Percutaneous pediculoplasty was performed in 5 lung cancer
      patients with osteolytic metastasis in 7 vertebral pedicles, 2 cases occurred in
      thoracic vertebral pedicles and 3 cases occurred in lumbar vertebral pedicles, 2
      cases had two loci involved. Under Multislice helical CT guidance, 2.5-5mL of
      polymethylmethacrylate mixture (ratio of polymer, moner, ultrafluid iodinated oil
      was 20g:10mL:3mL) had been injected into pathologic pedicles step by step after
      successful puncture using 13G needle. All cases had been followed-up in 2-5
      months. RESULTS: All cases had been successfully punctured. Pain relieved in all
      4 cases to some extent after percutaneous pediculoplasty. Two cases had bone
      cement leakage, 1 case with leakage into intervertebral foramen which led to
      nerve radicular pain, the pain disappeared 3 days later after intravenous
      mannitol and lower dose dexamethasone drips, and another 1 case with minor
      leakage into vertebral canal but without clinical symptoms. No spondyloptosis
      occurred in all cases after follow-up. CONCLUSIONS: CT-guided percutaneous
      pediculoplasty is a minimal injured, effective and safe method for osteolytic
      vertebral pedicular metastasis of lung cancer.

PMID- 21172163
TI  - [Iressa in the treatment of 24 cases of advanced non-small cell lung cancer
      patients who had failed to previous chemotherapy].
AB  - BACKGROUND: Iressa is the inhibitor of epidemic growth factor receptor and mainly
      used to treat non-small cell lung cancer (NSCLC). The aim of this study is to
      evaluate the antitumor efficacy and toxicity of Iressa in the treatment of
      advanced NSCLC patients who had failed to previous chemotherapy. METHODS: Twenty
      four patiets with advanced NSCLC who were previously treated with chemotherapy
      received 250mg of Iressa orally once daily until disease progressing or
      intolerable toxicity developing. Tumor evaluation was performed before treatment.
      Then for every four weeks after administration they recevied the examination;
      after administration for sixteen weeks, examination was repeated once every eight
      weeks. RESULTS: All twenty-four patients could be evaluated. One case got
      complete response, eight cases got partial response, three had no change and
      twelve had disease progression. So the response rate was 37.5%, the stable
      disease rate was 12.5%, and the clinical benifit rate was 50.0%. Median time to
      disease progressing was 87 days. All patients were followed up for two years and
      1- and 2-year survival rate was 33.3% and 12.5% respectively. The common adverse
      effects were skin reaction and diarrhea and no grade III or IV toxicity was
      observed. Two cases were suspected of pulmonary interstitial changes and the
      treatment ended. CONCLUSIONS: Iressa is effective in treatment of advanced NSCLC
      patients who had failed to previous chemotherapy and the adverse effects are
      tolerable. So Iressa is one of the best choice for NSCLC patients who need two or
      more line therapy.

PMID- 21172164
TI  - [Clinical trial of concurrent low-dose chemotherapy plus radiation vs sequential
      chemoradiotherapy for unresectable stage III non-small cell lung cancer].
AB  - BACKGROUND: Concurrent chemotherapy plus radiotherapy is a trend in treatment of
      non-small cell lung cancer (NSCLC), but the treatment program is rather
      complicated and the toxicity is more severe than chemotherapy or radiotherapy
      alone. The aim of this study is to evaluate the early response and toxicity of
      concurrent chemoradiotherapy. METHODS: Eighty unresectable stage IIIA-IIIB NSCLC
      patients pathologically proved were randomly divided into 2 groups. Group A:
      patients were treated with concurrent chemotherapy of vinorelbine (12.5mg/m2, on
      days 1, 8, 29, 36) and cisplatin (40mg/m2, on days 1, 8, 29, 36) (NP regimen)
      plus conventional radiotherapy. Patients were irradiated at 1.8-2.0Gy/Fx daily, 5
      days per week. The total dose was 60Gy/30-33 Fx. After the radiation, 3 cycles of
      NP regimen were performed, but the dose of vinorelbine was 25mg/m2. Group B:
      patients received sequential chemoradiotherapy. At first radiation was performed
      as same as group A. Then chemotherapy of NP (NVB 25mg/m2, on days 1 and 8, DDP
      80mg/m2, on day 1) was followed for 4-5 cycles. RESULTS: The overall response
      rate in concurrent and sequential groups was 80.0% and 57.5% respectively (Chi
      Square=4.71, P < 0.05). Incidences of grade III-IV acute radiation esophagitis
      and leukopenia were 47.5% and 65.0% in group A, and 25.0% and 42.5% in group B
      respectively (P < 0.05). The acute radiation pneumonitis rate was 32.5% in group
      A and 20.0% in group B (P > 0.1). CONCLUSIONS: Concurrent chemoradiotherapy is
      well tolerated in most unresectable stage IIIA-IIIB NSCLC patients. Its early
      response is better than sequential chemoradiotherapy.

PMID- 21172165
TI  - [Hyperthermia combined with intracavitary injection of drug for malignant pleural
      effusion].
AB  - BACKGROUND: Malignant pleural effusion is one of the common complications in
      patients with advanced lung cancer. Intracavitary injection of drug is a usual
      method, but it also exhibits unstable efficacy and obvious adverse reaction. The
      aim of this study is to evaluate the efficacy of hyperthermia combined with
      intracavitary injection of drug for malignant pleural effusion. METHODS: Fifty
      patients with malignant pleural effusion caused by lung cancer were randomized
      into two groups after puncture or closed drainage. Group A was treated with
      hyperthermia combined with intrapleural injection of cisplatin and interleukin-2.
      Group B was treated only with intrapleural injection of cisplatin and interleukin
      2. RESULTS: The response rate of pleural effusion was 88% in group A and 60% in
      group B (P=0.024). The quality of life in group A was significantly better than
      that in group B (P=0.013). CONCLUSIONS: Hyperthermia combined with intracavitary
      injection is effective and secure in treatment of malignant pleural effusion.

PMID- 21172169
TI  - Start of the influenza season 2010-11 in Europe dominated by 2009 pandemic
      influenza A(H1N1) virus.

PMID- 21172170
TI  - First identified case of VIM-producing carbapenem-resistant Klebsiella pneumoniae
      in the Republic of Ireland associated with fatal outcome.

PMID- 21172171
TI  - Ongoing outbreak of mumps affecting adolescents and young adults in Bavaria,
      Germany, August to October 2010.

PMID- 21172172
TI  - Spotlight on measles 2010: An ongoing outbreak of measles in an unvaccinated
      population in Granada,Spain, October to November 2010: an ongoing outbreak of
      measles in an unvaccinated population in Granada, Spain, October to November
      2010.
AB  - In September and October 2010, 13 primary measles cases were identified among
      unvaccinated persons aged between 9 and 32 years (median: 16.5) in 11 districts
      in Germany. All cases had attended meetings in Taize, France. This outbreak
      illustrates the risk of long distance spread of infectious diseases associated
      with international mass gatherings, and underlines the importance of closing
      immunisation gaps against measles by vaccinating non-immune adolescents and young
      adults.

PMID- 21172173
TI  - Spotlight on measles 2010: Increased measles transmission in Ferrara, Italy,
      despite high vaccination coverage, March to May 2010: increased measles
      transmission in Ferrara, Italy, despite high vaccination coverage, March to May
      2010.

PMID- 21172174
TI  - Spotlight on measles 2010: Measles outbreak in the Provence-Alpes-Cote d'Azur
      region, France, January to November 2010 - substantial underreporting of cases:
      measles outbreak in the Provence-Alpes-Cote d Azur region, France, January to
      November 2010 - substantial underreporting of cases.

PMID- 21172175
TI  - Spotlight on measles 2010: Measles outbreak among travellers returning from a
      mass gathering, Germany, September to October 2010.

PMID- 21172176
TI  - Spotlight on measles 2010: measles elimination in Europe - a new commitment to
      meet the goal by 2015.

PMID- 21172177
TI  - Welcome to the journal of Crohn's & colitis.

PMID- 21172178
TI  - Infliximab in paediatric inflammatory bowel disease.
AB  - Infliximab has been widely used in paediatric Crohn's disease, mainly in luminal
      and fistulous disease refractory to standard treatment and for extraintestinal
      manifestations. Moreover, there is growing experience with its use in refractory
      ulcerative colitis. Infliximab has shown similar efficacy and safety in children
      as in adult population. It is postulated that its early use in paediatric
      inflammatory bowel disease, as a bridging treatment until the onset of action of
      other immunomodulators, could reduce the use of steroids and change the natural
      history of the disease as well. The effect of infliximab on mucosal healing could
      also contribute to the normal growth and sexual maturation in these patients.

PMID- 21172166
TI  - Pharmacogenetics of antidepressant response.
AB  - Personalized medicine - the adaptation of therapies based on an individual's
      genetic and molecular profile - is one of the most promising aspects of modern
      medicine. The identification of the relation between genotype and drug response,
      including both the therapeutic effect and side effect profile, is expected to
      deeply affect medical practice. In this paper, we review the current knowledge
      about the genes related to antidepressant treatment response and provide
      methodologic proposals for future studies. We have mainly focused on genes
      associated with pharmacodynamics, for which a list of promising genes has been
      identified despite some inconsistency across studies. We have also synthesized
      the main results for pharmacokinetic genes, although so far they seem less
      relevant than those for pharmaco dynamic genes. We discuss possible reasons for
      these inconsistent findings and propose new study designs.

PMID- 21172179
TI  - Impact of inflammatory bowel disease on quality of life: Results of the European
      Federation of Crohn's and Ulcerative Colitis Associations (EFCCA) patient survey.
AB  - BACKGROUND: : The predominant symptoms of inflammatory bowel disease (IBD) are
      diarrhoea, abdominal pain, gastrointestinal bleeding, weight loss, malnutrition
      and fatigue. These symptoms can have substantial psychosocial implications and
      cause sufferers to limit their lifestyles, with consequent impact on quality of
      life (QoL). AIMS: : To survey the impact of IBD on peoples' lives as well as
      opinions of treatment and patient-doctor communication in a large European cohort
      of patients. SUBJECTS AND METHODS: : Seven organisations affiliated with the
      European Federation of Crohn's and Ulcerative Colitis Associations (EFCCA)
      distributed questionnaires to 12,200 members between May and August 2005. In
      total, 5636 responses were received and analysed using descriptive statistics.
      RESULTS: : Of 5576 patients with evaluable responses, 1000 (17.9%) were not
      currently receiving any treatment, and 3109 (55.8%) were currently receiving anti
      inflammatory/5-aminosalicylic acid, 1143 (25.9%) receiving immunomodulators, and
      1076 (19.3%) receiving steroids (biologics constituted 4%; however, at the time
      of this survey they were not approved for use in treating patients with UC).
      Three quarters were either very (n=2233, 40.0%) or somewhat (n=2010, 36.0%)
      satisfied with the results obtained from their current treatment medication. If
      given a choice, 4819 (86.4%) said they would rather try a new type of drug
      therapy than undergo surgery. However, only 2182 (39.1%) reported that their
      doctor talked to them about newly developed treatments. Three quarters (75.6%,
      n=4213) reported that symptoms affect their ability to enjoy leisure activities,
      while over two thirds (68.9%, n=3841) felt symptoms affected their ability to
      perform at work. However, nearly half (n=2666, 47.8%) reported that their doctor
      does not ask about the impact of symptoms on their QoL. For those patients who
      received immunomodulators, 72.7% reported QoL improvements (1462/2012) while
      72.8% reported QoL improvements with steroids (2622/3601). 75% of patients with
      CD who received biologic therapy (6% of responders) stated that their QoL
      improved following biologic therapy. CONCLUSIONS: IBD symptoms have a substantial
      impact on patients' lives, and QoL as well as new treatments should be an
      important feature of patient-physician discussions. The survey results may point
      to areas where support of IBD patients might be improved.

PMID- 21172180
TI  - Maintenance therapy for ulcerative colitis has no impact on changes in the extent
      of ulcerative colitis.
AB  - BACKGROUND AND AIM: Although the efficacy of maintenance remission therapy in
      ulcerative colitis (UC) has been proved in many studies, little is known about
      its possible effect on the extent of the disease. The aim of the present
      multicenter Belgian study was to evaluate the potential role of UC maintenance
      therapy on the colonic extension of the disease. MATERIALS AND METHODS: A total
      of 98 patients, 56 males, 42 females, mean age 52 years, range 22-82 years, from
      12 medical centers in Belgium, with an acute exacerbation of well-established,
      endoscopically and histologically proven left-sided UC, were included. The
      colonic extension was endoscopically determined at the time of the initial
      diagnosis and at the actual flare-up. The mean duration of UC was 93+72 months,
      median was 84 months, and range was 3-372 months. Active smoking was reported in
      only 7% of patients, while the majority were no-smokers (63%) or ex-smokers
      (30%). The median colonic extension at the time of initial diagnosis was 25 cm,
      range 2-70 cm from the anal merge. Sixty-six percent of the patients had
      quiescent disease without flare-ups during last year. The chi(2)-test was used
      for statistical analysis. RESULTS: 29/98 (29.6%) patients had not used any
      maintenance therapy in the last 3 months before the actual exacerbation. The most
      commonly used maintenance therapy was 5-ASA (43%), while combined therapy with 5
      ASA, corticosteroids or immunosuppresives (mainly azathioprine) in all possible
      combinations was reported by 29.6% of patients. The extent of UC had not changed
      in 50.7% and 51.7% of patients, respectively, with and without maintaining
      therapy (NS, p=0.99). Some degree of regression was observed in, respectively,
      21.7% and 20.7% (NS, p=0.99), and some degree of extension in, respectively,
      27.5% and 27.6% (NS, p=0.99). Furthermore, no relationship was found between
      changes in colonic extent and type of maintaining therapy, smoking habits or
      disease activity during the last year before the acute exacerbation. A tendency
      of beneficial effect of maintenance therapy on disease extent was observed in
      patients with continuous active disease of short duration. CONCLUSIONS: According
      to this multicenter study, maintenance remission therapy for left-sided UC was
      not found to have a statistically significant effect on colonic extension.
      Further long-term studies are necessary to confirm these results.

PMID- 21172181
TI  - The long-term efficacy of azathioprine does not wane after four years of
      continuous treatment in patients with steroid-dependent luminal Crohn's disease.
AB  - BACKGROUND: The long-term effectiveness of azathioprine, in Crohn's disease (CD)
      patients remains a matter of debate. This study aims at assessing the
      effectiveness and safety of azathioprine in patients treated continuously for
      less or more than 4 years. METHODS: Patients with steroid-dependent Crohn's
      disease in remission on azathioprine (2-2.5 mg/kg) for between 2 and 8 years were
      assigned into two groups. Patients in Group A were being treated continuously for
      2 to 4 years whereas patients in Group B for 4 to 8 years. Patients were followed
      every month for 1 year with physical examination and laboratory tests. Compliance
      with treatment was also assessed every month. Every 3 months the Crohn's Disease
      Activity Index (CDAI) was calculated and the quality of life (QOL) Inflammatory
      Bowel Disease Questionnaire (IBDQ) was completed. Colonoscopy with calculation of
      the Crohn's Disease Endoscopic Index of Severity (CDEIS) was performed at
      baseline and at the end of the study. The primary end point was relapse after 1
      year. Secondary end points were safety of treatment, QOL, and endoscopic healing.
      RESULTS: Fifty-eight patients were included in Group A and 42 in Group B. The
      relapse rates per protocol were 19.6% and 11.9%, respectively (p: not
      significant). There were no significant differences overall and at each time
      point of the study between the two treatment groups regarding compliance with and
      safety of treatment, CDAI, IBDQ, and CDEIS scores. Multifactorial analysis did
      not identify any factor influencing the remission of disease in any patient
      group. CONCLUSIONS: Long-term treatment with azathioprine of steroid-dependent
      Crohn's disease is efficacious and safe.

PMID- 21172182
TI  - Aberrant gastric apomucin expression in ulcerative colitis and associated
      neoplasia.
AB  - AIM: To evaluated the presence of gastric metaplasia in colonic mucosa of
      patients with ulcerative colitis and its relationship with dysplasia/neoplasia.
      MATERIAL AND METHODS: Ninety patients with UC were selected. The duration and the
      extent of disease were registered in all the cases. Biopsies were histologically
      and immunohistochemically assessed. Crypt distortion, goblet cell depletion,
      Paneth cell metaplasia and inflammatory activity were graded, as well as
      dysplasia and invasive neoplasia (absent or present). Monoclonal antibodies
      against the gastric apomucins MUC5AC (foveolar) and MUC6 (mucopeptic) were used.
      RESULTS: Neoplasia was observed in 16 patients, 8 non-invasive (dysplasia) and 8
      invasive (adenocarcinoma). MUC5AC and MUC6 were detected in 63 and 16 out the 90
      cases, 70.0% and 17.8%, respectively. The staining was patchy for both
      antibodies, affecting groups of cells more often than isolated cells. The
      presence of MUC5AC correlated positively with inflammatory activity and goblet
      cell depletion (R=0.231, p=0.03 and R=0.211, p=0.048, respectively). The
      expression of MUC6 correlated positively with age (R=0.297, p=0.005), duration of
      disease (R=0.287, p=0.008), extent of disease (R=0.342, p=0.001), crypt
      distortion (R=0.276, p=0.01) and the presence of neoplasia (R=0.483, p<0.00).
      There was no correlation between Paneth cell metaplasia and apomucin expression.
      CONCLUSIONS: Our study demonstrates the aberrant expression of gastric apomucins
      in UC and suggests that MUC5AC is associated with inflammation while MUC6 is
      related to the presence of neoplasia. The demonstration of metaplastic cell
      lineages preceding dysplasia supports the biological link between inflammation
      and neoplasia, MUC6 emerging as a putative biomarker of dysplasia in ulcerative
      colitis patients.

PMID- 21172183
TI  - Herpes simplex virus colitis complicating ulcerative colitis: A case report and
      brief review on superinfections.
AB  - In patients with inflammatory bowel disease herpes simplex virus infection has
      been described as a major cause of morbidity and mortality, especially in
      immunocompromised individuals. Here we present the case of a 35-year old woman
      with an exacerbation of ulcerative colitis caused by herlpes simplex virus
      infection (HSV-2). The diagnosis was confirmed histologically following subtotal
      colectomy. After intravenous treatment with aciclovir for 2 weeks postoperative
      hematochezia stopped. Herpes simplex virus colitis is a rare but potentially
      fatal complication of immunosuppressive treatment in patients with inflammatory
      bowel disease. Prompt diagnosis and efficient antiviral therapy are mandatory to
      improve prognosis.

PMID- 21172184
TI  - Probiotics for preventing relapse or recurrence in Crohn's disease involving the
      ileum: Are there reasons for failure?
AB  - In contrast to ulcerative colitis and pouchitis, benefits of probiotic therapy in
      preventing recurrence/relapse in Crohn's disease (mostly involving the ileum) are
      far from being proven. The lack of response in this setting does not seem
      attributable to a lower relevance of dysbiosis in ileal Crohn's disease, since
      this - or at least the presence of increased mucosal amounts of potentially
      pathogen bacteria - has been proven to occur in the ileum of Crohn's disease
      patients. Available data indicate that whereas in ulcerative colitis (and to a
      lesser extent in colonic Crohn's disease) the innate immune response is enhanced,
      it is constitutively depressed in ileal Crohn's disease. Therefore, attempts to
      modify the composition of intestinal microflora in colonic IBD or pouchitis by
      means of probiotics do make sense. In contrast, supplying additional bacteria
      (even being probiotics) to an ileum with decreased antibacterial defence does not
      seem reasonable. In fact, the presence of intestinal contents has been reported
      to be related to postoperative recurrence in ileo-caecal Crohn's disease, and
      antibiotic treatment in effective to prevent its development.

PMID- 21172185
TI  - The effects of NOD2/CARD15 mutations on the function of the intestinal barrier.
AB  - NOD2 variants have been identified to be a susceptibility factor for Crohn's
      disease. The NOD2 protein is an intracellular sensor of the bacterial wall
      product muramyl dipeptide (MDP) and activates the transcription factor NF-kappaB
      upon MDP-binding. NOD2 variants are associated with reduced NF-kappaB activation
      and reduced production of epithelial derived antibacterial peptides such as
      defensins. A reduced expression of defensins is described and found in patients
      with Crohn's disease and ulcerative colitis especially when NOD2 variants are
      present. Furthermore recent evidence from mouse models suggests that the ability
      of intestinal epithelial cells to activate NF-kappaB upon bacterial stimulation
      protects from mucosal inflammation. Taken together these data indicate that NOD2
      mediated NF-kappaB activation, subsequent induction of anti-microbial peptides
      such as defensins and induction of cytokine expression are essential for the
      function of the intestinal barrier and for the prevention of bacterial
      translocation. The data indicate why a defect in the induction of this acute
      defense response is associated with chronic inflammation. Invading bacteria that
      cannot be readily detected and eliminated may start a backup mechanism of
      inflammation finally resulting in chronic inflammatory reaction followed by
      further impairment of the mucosal barrier.

PMID- 21172186
TI  - Pulmonary abnormalities in inflammatory bowel disease.
AB  - Extraintestinal manifestations of inflammatory bowel disease (IBD) is a common
      clinical problem affecting up to half of all IBD patients; pulmonary disease,
      however, ranks among less common extraintestinal manifestations of IBD. Pulmonary
      disease in patients with IBD is most frequently drug induced due to treatment
      with sulfasalazine or mesalamine leading to eosinophilic pneumonia and fibrosing
      alveolitis or due to treatment with methotrexate leading to pneumonitis.
      Recently, various opportunistic infections have been shown to be a further
      important cause of pulmonary abnormalities in those IBD patients who are treated
      with immunosuppressants such as anti TNF-alpha monoclonal antibodies,
      methotrexate, azathioprine or calcineurin antagonists. In not drug related
      pulmonary disease a wide spectrum of disease entities ranging from small and
      large airway dysfunction to obstructive and interstitial lung disorders exist.
      Patients with lung disorders and inflammatory bowel disease should be evaluated
      for drug-induced lung disease and opportunistic infections prior to considering
      pulmonary disease as an extraintestinal manifestation of inflammatory bowel
      disease.

PMID- 21172187
TI  - A study in three European IBD cohorts confirms that the ATG16L1 c.898A>G
      (p.Thr300Ala) variant is a susceptibility factor for Crohn's disease.
AB  - BACKGROUND AND AIMS: A recent study reported that a nonsynonymous SNP rs2241880
      (c.898A>G, p.Thr300Ala) within ATG16L1 confers susceptibility to Crohn's disease
      (CD). We analyzed ATG16L1 c.898A>G in three independent European inflammatory
      bowel disease (IBD) cohorts from Germany, Hungary and the Netherlands. METHODS:
      In total, we included 910 European IBD patients and compared the ATG16L1 c.898A>G
      genotype frequency with 707 ethnically matched healthy controls. We included
      patients from 3 populations originating from Germany (CD n=310; ulcerative
      colitis [UC] n=179), Hungary (CD n=147; UC n=117), and the Netherlands (CD
      n=157). Subtyping analysis was performed in respect to CARD15 alterations and
      clinical characteristics. RESULTS: We found a highly significant association of
      c.898A>G to CD. The association was significant (p=0.0005) for the total CD
      cohort but also for the individual populations from Germany (p=0.02) and
      Netherlands (p=0.02) whereas in the Hungarian CD patients a clear trend was
      observed (p=0.19; OR 1.227, 95% CI 0.910; 1.654). No association was found
      between c.898A>G and UC. No statistical interactions were observed between
      ATG16L1 c.898A>G and CARD15 variants. Furthermore no association to a CD
      subphenotype was detected. CONCLUSIONS: We confirm that ATG16L1 variant c898A>G
      confers a risk variant for CD but is not associated with a distinct CD phenotype.

PMID- 21172188
TI  - Non-adherence to treatment in inflammatory bowel disease in Czech Republic.
AB  - OBJECTIVE: : To assess overall non-adherence to the treatment among patients with
      Crohn's disease (CD) and ulcerative colitis (UC). PATIENTS AND METHODS: : 396
      inflammatory bowel disease (IBD) patients were enrolled in the study (200 males,
      196 females, 210 CD, 186 UC) and fulfilled the questionnaire to assess their non
      adherent behaviour during the treatment. The data was analysed using factor
      analysis. RESULTS: : Overall intentional non-adherence was reported by 32% of
      patients. A 12% of patients reported they at least once discontinued the
      treatment. Voluntary dose reducing was reported by 19% of patients. An 11% of
      patients occasionally non-refill the medication in time. There were no
      differences in intentional adherence between males and females, disease type,
      previous bowel surgery, marital, smoking and non-smoking statuses. A 42% of
      patients reported unintentional non-adherence. Factor analysis proved non
      adherent patients are more likely to have a higher activity of the disease (
      tau=0.109, p=0.008). CONCLUSIONS: : The overall intentional non-adherence is
      relatively high among IBD patients and a gastroenterologist's attention should be
      focused on it. Our results stimulate discussion how to improve education of the
      patients with inflammatory bowel disease and accent importance of the maintenance
      therapy to them.

PMID- 21172189
TI  - Limited ileo-caecal resection for localised Crohn's disease in childhood:
      Clinical outcome and predictors of further surgery.
AB  - OBJECTIVES: To investigate the outcome of limited ileo-caecal resection in
      children with localised Crohn's disease (CD) and determine predictors of further
      surgery. METHODS: Review of children diagnosed with CD and operated on for ileo
      caecal disease from 1995 to 2005. Age at diagnosis, endoscopic disease
      distribution, indication for surgery, site of recurrence and date of last follow
      up were recorded. Surgery required removal of only the ileo-caecal junction and
      caecal pole with removal of the minimum terminal ileal length. RESULTS: Thirty
      seven children underwent intestinal resection. Time between primary operation and
      most recent follow-up was 3.8 years (range 1 month-8.8 years). Indications for
      surgery were obstruction/stricture (20), treatment-resistant disease (13) and
      abscess/perforation peritonitis (4). Follow-up was available in 32. Nine (28%)
      required re-laparotomy. Median time to second laparotomy was 12 months (range 4
      58 months). Eighteen children required no endoscopies after surgery (median
      follow-up 3.4 years). CONCLUSION: Most conservative surgery occurs about 2 years
      after diagnosis. About 1 in 4 children have a further laparotomy within 12
      months. Over half of these require division of adhesions. Limited ileo-caecal
      resection for localized Crohn's disease is not associated with early peri
      anastomotic recurrence. Developments in laparoscopic surgery are likely to
      further reduce complications from adhesions.

PMID- 21172190
TI  - Effect of phenotype on health care costs in Crohn's disease: A European study
      using the Montreal classification.
AB  - BACKGROUND: Crohn's disease (CD) is a chronic inflammation of the
      gastrointestinal tract associated with life-long high health care costs. We aimed
      to determine the effect of disease phenotype on cost. METHODS: Clinical and
      economic data of a community-based CD cohort with 10-year follow-up were analyzed
      retrospectively in relation to Montreal classification phenotypes. RESULTS: In
      418 patients, mean total costs of health care for the behavior phenotypes were:
      nonstricturing-nonpenetrating 1690, stricturing 2081, penetrating 3133 and
      penetrating-with-perianal-fistula 3356 ?/patient-phenotype-year (P<0.001), and
      mean costs of surgical hospitalization 215, 751, 1293 and 1275 ?/patient
      phenotype-year respectively (P<0.001). Penetrating-with-perianal-fistula patients
      incurred significantly greater expenses than penetrating patients for total care,
      diagnosis and drugs, but not surgical hospitalization. Total costs were similar
      in the location phenotypes: ileum 1893, colon 1748, ileo-colonic 2010 and upper
      gastrointestinal tract 1758 ?/patient-phenotype-year, but surgical
      hospitalization costs differed significantly, 558, 209, 492 and 542 ?/patient
      phenotype-year respectively (P<0.001). By multivariate analysis, the behavior
      phenotype significantly impacted total, medical and surgical hospitalization
      costs, whereas the location phenotype affected only surgical costs. Younger age
      at diagnosis predicted greater surgical expenses. CONCLUSIONS: Behavior is the
      dominant phenotype driving health care cost. Use of the Montreal classification
      permits detection of cost differences caused by perianal fistula.

PMID- 21172191
TI  - Intravenous iron therapy restores functional iron deficiency induced by
      infliximab.
AB  - BACKGROUND AND AIMS: Infliximab (IFX) and iron sucrose (FeS) are of high value in
      inflammatory bowel disease (IBD). We aimed to assess the relative role of both
      therapies in IBD related anaemia and their safety when used in combination.
      METHODS: IBD patients with anaemia receiving a first series of FeS infusions in
      addition to IFX were prospectively followed. We investigated serum kinetics of
      erythropoietin (EPO), soluble transferrin receptors (sTFRs) and vascular
      endothelial growth factor (VEGF). RESULTS: Data analysis included 87 patients of
      whom 49.4% achieved the target Hb level of 12.0 g/dL. IFX resulted in a
      significant increase of EPO and sTFR compared to baseline pre-IFX levels (p=0.029
      and p=0.005 respectively) and after a 12-week combined FeS and IFX treatment, EPO
      and sTFR levels dropped significantly compared to pre-FeS levels (p<0.001 for
      both). Infusion related adverse events were recorded in 2 IFX treated patients
      (2.3%, 0.7% of the infusions) and were mild. Disease activity and quality of life
      were not affected. CONCLUSIONS: In anaemic IBD patients treated with IFX,
      combined administration of FeS is safe. Infliximab significantly increases serum
      EPO and sTFR levels resulting in an increased functional iron deficiency, which
      is restored after combined treatment with I.V. iron sucrose.

PMID- 21172192
TI  - NOD2 activity modulates the phenotype of LPS-stimulated dendritic cells to
      promote the development of T-helper type 2-like lymphocytes - Possible
      implications for NOD2-associated Crohn's disease.
AB  - Sensing of commensal microorganisms via Toll-like receptors (TLR) in the gut is
      essential for maintaining intestinal homeostasis in healthy individuals.
      Conversely, Crohn's disease is characterised by an inappropriate T helper-type 1
      (Th1)-mediated immune response towards these same microorganisms. NOD2 is
      expressed by dendritic cells (DC) and mediates responses to bacterial muramyl
      dipeptides (MDP). Mutations in NOD2 (CARD15) have recently been associated with
      susceptibility to Crohn's disease although the underlying mechanisms have yet to
      be established. We investigated the functional outcome of NOD2 and TLR4-mediated
      activation in monocyte-derived DC from wild-type NOD2 healthy controls and NOD2
      frame-shift mutation-carrying Crohn's disease patients. In wild-type DC, MDP
      acted synergistically with LPS to amplify inflammatory cytokine production,
      enhance co-stimulatory molecule expression, and produce DC that promoted the
      proliferation of naive, allogeneic, CD4(+) T lymphocytes with a Th2-like cytokine
      profile. By contrast, DC carrying homozygous NOD2 mutations were unable to react
      to MDP, responded to LPS only, and promoted the development of Th1 cells. These
      results suggest activation of the NOD2 pathway in DC modulates their response to
      TLR agonists and regulates their ability to induce polarised Th1 responses. As a
      consequence, Crohn's disease patients with defective NOD2 may be predisposed to
      the generation of strongly polarised Th1 responses against common commensal
      microorganisms.

PMID- 21172193
TI  - An unusual case of Crohn's disease with unresponsive pleural exudates. Is Crohn's
      disease finally a systemic immunological disorder?
AB  - Crohn's disease has been infrequently associated with various respiratory
      manifestations. Reports of pleural effusions in Crohn's disease are even sparser,
      but differential diagnosis is rich, with causes either associated with the
      disease or being independent. Processes directly or indirectly related to
      therapy, entities overlapping with Crohn's disease in pathogenesis and common
      causes of effusions should all be considered, under the guidance of laboratory
      testing and imaging. We report here an unusual case of bilateral pleural
      effusions unresponsive so far to medical therapy, in a patient with long-standing
      Crohn's disease and several features of autoimmunity. A short review of the
      literature is presented, the differential diagnosis is outlined and the systemic
      immunological profile of Crohn's disease is discussed.

PMID- 21172194
TI  - European evidence-based Consensus on the diagnosis and management of ulcerative
      colitis: Definitions and diagnosis.

PMID- 21172195
TI  - European evidence-based Consensus on the management of ulcerative colitis:
      Current management.

PMID- 21172196
TI  - European evidence-based Consensus on the management of ulcerative colitis:
      Special situations.

PMID- 21172197
TI  - Complete remission of a primary rectal lymphoma on ulcerative colitis, after
      withdrawal of azathioprine and infliximab.
AB  - A 45-year-old woman was diagnosed with ulcerative colitis and treated with
      mesalazine, prednisone and, finally, azathioprine and infliximab. Colonoscopy
      revealed a rectal ulcer, identified by biopsy as a large cell B-lymphoma,
      positive for leukocyte common antigen (LCA), CD 20 and LMP-1 and negative for CD
      3. Three months after withdrawal of all immunosuppressors, a proctocolectomy was
      performed. The resection specimen contained an area of B-cell polymorphic
      hyperplasia, but no residual tumour. The patient remains well after 2 years of
      follow-up, without any further antineoplastic therapy.

PMID- 21172198
TI  - The challenges of medication non-adherence in ulcerative colitis: Practical
      suggestions to help patients.

PMID- 21172199
TI  - Stem cells as potential novel therapeutic strategy for inflammatory bowel
      disease.
AB  - Hematopoietic stem cell transplantation and mesenchymal stromal cell therapy are
      currently under investigation as novel therapies for inflammatory bowel diseases.
      Hematopoietic stem cells (HSC) are thought to repopulate the immune system and
      reset the immunological response to luminal antigens. Mesenchymal stromal cells
      (MSC) are cells that have the capacity to differentiate into wide variety of
      distinct cell lineages and suppress immune responses in vitro and in vivo. Recent
      results from animal models and early human experience in graft-versus-host
      disease but also Crohn's Disease suggest that ex vivo expanded MSCs may have
      clinically useful immunomodulatory effects.

PMID- 21172200
TI  - Capsule endoscopy in Crohn's disease - Indications and reservations 2008.
AB  - Capsule endoscopy (CE) was found to be an effective tool in diagnosis of small
      bowel pathology. This review will focus on its role in Crohn's disease. Its role
      in patients with suspected Crohn's disease (CD) is described. CE has an
      established role for diagnosing CD when other tests are negative, though it is
      not a first line investigative tool in these patients. Over diagnosis is of
      concern. Its use in established CD remains an open question. It can provide exact
      mapping of small bowel disease before surgery, and might have impact on the
      treatment of the disease. It may have role in monitoring mucosal healing, which
      is becoming a target of therapy, and may help establish the exact diagnosis in a
      limited group of patients with indeterminate colitis. Retention of CE might
      occur. It is of low rate in patients with suspected CD and higher in patients
      with known CD but clinical obstruction is extremely rare. Economic considerations
      are a limit to a wider application of the CE.

PMID- 21172201
TI  - Serological markers are associated with disease course in ulcerative colitis. A
      study in an unselected population-based cohort followed for 10 years.
AB  - OBJECTIVES: Perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) and anti
      Saccharomyces cerevisiae antibody (ASCA) have been proposed as markers for
      diagnosis and for subtyping of inflammatory bowel disease (IBD). The aim of this
      study was to investigate the association of p-ANCA and ASCA with a 10-year
      disease outcome in terms of cumulative rate of colectomy and relapse in a
      population-based European inception cohort of ulcerative colitis (UC) patients.
      METHODS: Serum samples from 432 consenting patients were analysed for p-ANCA and
      ASCA. The results were compared with the cumulative colectomy rate, relapsing
      disease and total number of relapses. We used multiple regression analyses
      adjusted for age, sex, residence, disease extent at diagnosis, smoking, familial
      IBD and drug treatment to study the relationship between serological values and
      disease course. RESULTS: The relapse rate was higher in the p-ANCA-positive
      patients: 82% (95% confidence interval [CI] 75-89%) compared with 67% (CI 62-72%,
      p=0.011) in the p-ANCA-negative patients. The risk of relapsing disease course
      was higher by a factor of 1.4 (CI 1.1-1.8, p=0.009) for p-ANCA-positive patients
      than for p-ANCA-negative patients, and the corresponding relative risk (RR) for
      the total number of relapses was 1.9 (CI 1.7-2.1, p<0.001). In ASCA-positive
      patients RR for the total number of relapses was 1.8 (CI 1.5-2.1, p<0.001). No
      significant association with colectomy rate was found for the presence of either
      p-ANCA or ASCA. CONCLUSION: UC patients positive for p-ANCA and possibly for ASCA
      may have a more unfavourable long-term disease outcome in terms of relapse than
      UC patients without these markers.

PMID- 21172202
TI  - Patients with ulcerative colitis responding to steroid treatment up-regulate
      glucocorticoid receptor levels in colorectal mucosa.
AB  - BACKGROUND AND AIMS: Glucocorticosteroid treatment (GCS) is effective for attacks
      of ulcerative colitis (UC). However, 25-30% of patients fails to respond and may
      be considered steroid resistant. Glucocorticoid receptors (GR) mediate the
      effects of GCS. Colorectal mucosa levels of GR and NF-kappaB were analysed
      before, during and after treatment with GCS-compounds. METHODS: Patients with
      moderate-severe attacks of ulcerative colitis were included. Patients undergoing
      colonoscopy with normal finding served as controls. GR and NF-kappaB levels in
      colorectal mucosa were analysed by Western Blotting and the DNA-binding activity
      of NF-kappaB by EMSA. RESULTS: Twenty-eight patients and seven controls were
      included. Ten patients were judged clinically steroid resistant. Responders had
      significantly higher levels of GR in colorectal mucosa after one week of
      treatment than non-responders (P=0.039) and significantly higher levels of GR
      were found in responders in remission as compared to before treatment (P=0.013).
      NF-kappaB levels did not differ between the groups at first visit. Increasing
      levels were found only in responders as remission was obtained (P=0.031). EMSA
      detected 20% lower DNA-binding of NF-kappaB in responders in remission as
      compared to first visit (P=0.021). CONCLUSION: GR levels increase in UC-patients
      responding to GCS-therapy but not in steroid resistant patients and may be the
      reason for the lack of steroid-efficacy. Increasing NF-kappaB levels were found
      in responders attaining remission, possibly reflecting a lower turnover. A
      decrease in DNA-binding of NF-kappaB was found in these patients, perhaps because
      of the increased GR levels counteracting NF-kappaB activity.

PMID- 21172203
TI  - Prevalence of Inflammatory Bowel Disease in the Canton of Vaud (Switzerland): A
      population-based cohort study.
AB  - BACKGROUND AND AIMS: Because of the changing epidemiology of Inflammatory Bowel
      Diseases (IBD), we set out to characterize the population-based prevalence of
      Crohn's Disease (CD) and Ulcerative Colitis (UC) in a defined population of
      Switzerland. METHODS: Adult IBD patients were identified by a cross-matched
      review of histological, hospital and gastroenterologist files throughout a
      geographical defined population (Canton of Vaud). Demographic factors
      statistically significantly associated with prevalence were evaluated using a
      stepwise Poisson regression analysis. Results were compared to IBD prevalence
      rates in other population-based studies and time trends were performed, based on
      a systematic literature review. RESULTS: Age and sex-adjusted prevalence rates
      were 205.7 IBD (100.7 CD and 105.0 UC) cases per 10(5) inhabitants. Among 1016
      IBD patients (519 CD and 497 UC), females outnumbered males in CD (p<0.001), but
      males were more represented in elderly UC patients (p=0.008). Thus, being a male
      was statistically associated with UC (Relative Risk (RR) 1.25; p=0.013), whereas
      being a female was associated with CD (RR 1.27; p=0.007). Living in an urban zone
      was associated with both CD and UC (RR 1.49; p<0.001, 1.63; p<0.001,
      respectively). From 1960 to 2005, increases in UC and CD prevalences of 2.4%
      (95%CI, 2.1%-2.8%; p<0.001) and 3.6% (95%CI, 3.1%-4.1%; p<0.001) per annum were
      found in industrialised countries. CONCLUSIONS: Extrapolating our data to all of
      Switzerland yields an estimate of 12,000 IBD cases for the country, or 1 in 500
      inhabitants. Our study gives support to an increase in IBD prevalence in Europe.

PMID- 21172204
TI  - Development of pouchitis following ileal pouch-anal anastomosis (IPAA) for
      ulcerative colitis: A role for serological markers and microbial pattern
      recognition receptor genes.
AB  - BACKGROUND AND AIMS: Pouchitis, the most common complication after
      proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis,
      has been attributed to altered composition of faecal flora. We investigated the
      role of antimicrobial and antiglycan antibodies and polymorphisms in microbial
      pattern recognition receptor genes. METHODS: Clinical charts of all 184 patients
      with ulcerative colitis who underwent IPAA between 1990-2004 were reviewed for
      pre- and post-operative disease course. RESULTS: Follow-up data were available in
      172 patients [67 female, median age at proctocolectomy 39.1 years]. During a
      median follow-up of 6.7 (interquartile range 3.7-10.5) years, 80 patients (47%)
      developed at least one episode of pouchitis. Cox proportional-hazard regression
      identified extra-intestinal manifestations [HR 1.78 (95%CI 1.10-2.88), p=0.020],
      a GT/TT genotype at Toll-like-receptor-1 S87I [HR 1.64 (1.01-2.66), p=0.047],
      anti-chitobioside carbohydrate antibodies [HR 2.03 (1.11-3.70), p=0.021] and
      young age at diagnosis [p=0.003] to be independently associated with pouchitis.
      Factors associated with chronic pouchitis, diagnosed in 33 patients (19%), were
      extra-intestinal manifestations [HR 2.45 (1.07-5.62), p=0.034], backwash ileitis
      [HR 3.15 (1.10-9.00), p=0.032], outer-membrane porin antibodies [HR 2.67 (1.20
      5.94), p=0.016] and young age at proctocolectomy [p=0.008]. CONCLUSIONS: : The
      reported association with antibodies and Toll-like-receptor-1 supports the
      pathophysiological role of the faecal flora in the development of pouchitis.

PMID- 21172205
TI  - Incidence of ulcerative colitis and Crohn's disease in Danish children: Still
      rising or levelling out?
AB  - AIM: To describe the development in incidence and prevalence of paediatric
      inflammatory bowel disease (IBD) in Eastern Denmark during a six-year period.
      METHODS: All patients <15 years with IBD in Eastern Denmark in the two following
      periods were included: 1) 1.1.1998-31.12.2000 and 2) 1.1.2002-31.12.2004. The
      mean background population (children <15 years) in Eastern Denmark was 421,898
      persons in period 1 and 439,443 persons in period 2. Patients were identified
      using the ICD-10 classification (DK500-519). The following data were extracted
      from the files: diagnosis, change in diagnosis, age at diagnosis, localisation,
      extra-intestinal symptoms, surgery and county of residence. Incidence and
      prevalence for ulcerative colitis (UC), Crohn's disease (CD) and indeterminate
      colitis (IC) were calculated per 100,000 children <15 years. RESULTS: 98 patients
      (50 UC, 44 CD, 4 IC), median age 9.8 years (range 2-14) and 12.8 (range 0.5-14)
      for UC and CD, respectively, were identified in period 1. In the second period
      145 patients (70 UC, 64 CD, 11 IC) were included with a median age of 11 years
      (range 1-14) and 12.5 (range 0.5-14) for UC and CD, respectively. The prevalence
      of IBD was 15.8 and 20.3 in 1998-2000 and 2002-2004, respectively. The incidence
      of IBD was 4.3 (UC: 1.8; CD: 2.3; IC: 0.2) and 6.1 (UC: 2.6; CD: 3.1; IC: 0.3),
      respectively, for the two periods (p>0.05). CONCLUSIONS: In our study we found an
      insignificant increase in the incidence of both CD and UC, indicating that the
      previously reported rising incidence might be levelling out.

PMID- 21172206
TI  - Risk factors for ulcerative colitis: A population-based, case-control study in
      Spain.
AB  - BACKGROUND: Environmental factors seem to be very important in the aetiology of
      Ulcerative Colitis (UC), with smoking, contraceptive use, and hygiene being the
      factors most commonly linked to disease. AIM: To analyse the association between
      different risk factors and development of UC in our community. PATIENTS AND
      METHODS: This is a case-control, population-based study. The UC population
      consists of an inception-case population of all cases diagnosed, using Lennard
      Jones criteria, in our community from 1st February 1992 to 31st January 1995 that
      were prospectively included. Controls were selected from healthy population and
      matched with patients for age, sex and rural/urban habitat. We used the SPSS/PC+
      software, EpiInfo and Statistix for statistical analysis, giving the rates as
      point estimates and 95% confidence intervals (95%CI) or as mean+/-standard
      deviation in quantitative variables. For multivariate analysis we used
      conditional logistic regression. RESULTS: 205 patients were diagnosed of UC. 38
      patients (18.5%) with UC were smokers, compared with 84 (40.8%) controls
      (p<0.001). Smoking behaved as a protector factor for UC (OR=0.55 (CI 95% 0.33
      0.92) and ex-smoker acted as a risk factor (OR=1.94 (CI 95% 1.14-3.34). After the
      multivariate analysis, both associations were maintained. We did not detect
      statistical differences in the analysis of previous appendectomy, childhood
      hygiene or oral contraceptive use. Five of the 12 cases with family aggregation
      had first-degree relatives and 7 of them second-degree relatives. None of the
      controls had previous IBD history (p=0.0002). CONCLUSION: Ex-smoking and previous
      family history of inflammatory bowel disease appeared as risk factors for
      developing ulcerative colitis while current smoking behaved as a protective
      factor in this population.

PMID- 21172208
TI  - Obstructing giant post-inflammatory polyposis in ulcerative colitis: Case report
      and review of the literature.
AB  - BACKGROUND: Post-inflammatory polyps >15 mm in diameter or length are termed
      "giant". This benign and rare sequel of ulcerative colitis or colonic Crohn's
      disease can mimic colorectal carcinoma. OBJECTIVE: To illustrate this rare
      complication of inflammatory bowel disease and outline the characteristic
      radiological, endoscopic and histopathological features, by reviewing all
      previously published cases of giant post-inflammatory polyps in the English
      literature. RESULTS: Reports of 81 giant post-inflammatory polyps in 78 patients
      were identified by systematic review of the literature. The incidence of giant
      post-inflammatory polyps is related to the extent of ulcerative colitis
      (incidence: 0%, 30%, and 70%, in proctitis, left-sided, and extensive disease,
      respectively). These lesions are typically located in the transverse or
      descending colon. Giant post-inflammatory polyps are as common in Crohn's disease
      (n=36) as in ulcerative colitis (n=42, 54%). Clinical presentations varies,
      including pain (n=29), rectal bleeding (n=20), diarrhoea (n=19), luminal
      obstruction (n=15), or a palpable mass (n=11). Symptomatic presentation results
      in surgical resection. Clinical details and outcomes are comprehensively
      tabulated. CONCLUSION: Recognition of this rare entity will prevent unnecessary
      radical surgical resection for presumed carcinoma. It highlights the need for
      clinical, radiological, endoscopic and histopathological correlation.

PMID- 21172207
TI  - Genetic and environmental factors as predictors of disease severity and extent at
      time of diagnosis in an inception cohort of inflammatory bowel disease,
      Copenhagen County and City 2003-2005.
AB  - BACKGROUND AND AIMS: The etiology of the inflammatory bowel diseases (IBD),
      Crohn's disease (CD) and ulcerative colitis (UC) remains unknown. We aimed to
      investigate the influence of genetic, serological, and environmental factors on
      phenotypic presentation of IBD at diagnosis in a population-based Danish
      inception cohort from 2003-2005. METHODS: Three-hundred-forty-seven (62%) of 562
      cohort patients were genotyped. ASCA and p/c-ANCA were determined and patients
      answered a questionnaire concerning environmental factors with possible influence
      on IBD. RESULTS: Fourteen percent of CD patients vs. 11% of controls were
      positive for common CARD15 mutation (ns), whereas more CD patients than healthy
      controls were homozygous for the OCTN-TC haplotype (p=0.03). ASCA was more common
      in CD (22%) than UC (14%) (p=0.045) and was related to age and localization of
      CD. p-ANCA was more frequent in UC (p=0.00001) but was related to pure colonic CD
      (p=0.0001). Sugar consumption was significantly higher in CD patients than in UC
      patients (p=0.0001) and more CD patients than UC patients had undergone
      appendectomy prior to IBD diagnosis (p=0.03). A possible relation between
      tonsillectomy and disease severity in CD, and a relation between use of oral
      contraception and disease localization of UC to rectum/left-sided colon were
      found. CONCLUSIONS: In this cohort of unselected IBD patients we found a very low
      frequency of mutations in IBD susceptibility genes and observed a greater impact
      of ASCA and ANCA than of genetic factors on disease phenotypes. In addition,
      several environmental factors seemed to influence disease occurrence and disease
      presentation in both UC and especially CD.

PMID- 21172209
TI  - IBD patients need in health quality of care ECCO consensus.
AB  - INTRODUCTION: : Inflammatory bowel diseases (IBD) is a lifelong disorder with
      increasing incidence and prevalence. IBD primarily affects young people's
      productivity in addition to direct and indirect costs. The chronic nature of the
      disease and the patients' requirement of frequent and easy access to the Health
      Care providers regarding lifelong medication, social and psychological support
      and regular follow-up in out-patient clinics are important considerations to
      address. AIM AND METHODS: : To define IBD patient needs in Quality of Health Care
      (QoHC) in Europe based on up- to date available evidence. The working group
      consisted of doctors, nurses and patient organizations from 12 European countries
      and Israel. Pub Med searching was performed as defined in the Delta Method. Each
      recommendation was graded (RG) in accordance with level of evidence (EL) based on
      Evidence Based Medicine, Oxford Centre. During UEGW 2007 the group reconvened to
      agree on the final version for each chapter of guideline statement RESULTS: : Pub
      Med search led to 6 RCT, 7 reviews, 63 original articles, but no meta-analysis
      regarding "Information"; "Education"; "Primary Care", "Quality of life",
      "Psychological help" and "Benchmarking of Health Care systems" in IBD. Seven ECCO
      statements have been worked out. CONCLUSION: : Evidence-based medicine in QoHC is
      limited. It is concluded that optimizing QoHC by "information"; "education",
      "benchmarking" and "psychological analysis" helps the patient to understand the
      disease and comply with its therapy, increasing QoL, reducing depression and
      anxiety. Future aspects regarding more evidence-based science and optimization of
      QoHC in IBD throughout Europe have been proposed.

PMID- 21172211
TI  - Osteoporosis in inflammatory bowel disease.
AB  - Half of all patients with inflammatory bowel disease show a significant reduction
      of their bone mass during the course of their chronic inflammatory disease. In
      contrast to women with postmenopausal osteoporosis these patients are much
      younger and a significant subgroup develops vertebral fractures which are mostly
      asymptomatic. The activity of the chronic inflammatory disease and the steroid
      treatment leads to bone loss predominantly through the TNFalpha-driven
      osteoprotegerin system. Clinical useful genetic markers to identify patients at
      risk for fractures have not been developed so far. Long-term clinical remission
      leads in most patients to normalisation of the bone density. Patients with
      reduced bone density should be substituted with calcium and vitamin D. Patients
      with vertebral fractures should receive bisphosphonates.

PMID- 21172212
TI  - High prevalence of low bone mineral density in patients with Inflammatory Bowel
      Disease in the setting of a peripheral Dutch hospital.
AB  - BACKGROUND AND AIMS: Osteopenia and osteoporosis are frequently encountered in
      patients with Inflammatory Bowel Disease (IBD). Our aims were to evaluate the
      actual practice of screening for low bone mineral density (BMD) by dual energy X
      ray absorptiometry (DEXA), to determine the prevalence of low BMD and to
      investigate the risk factors associated with a low BMD in the IBD population of a
      regional Dutch hospital. METHODS: A retrospective chart review was performed in
      474 patients (259 with ulcerative colitis, 210 with Crohn's disease and 5 with
      indeterminate colitis). DEXA results and potential predictive factors of low BMD
      were documented. Predictive factors of low BMD were assessed by logistic
      regression. RESULTS: DEXA was performed in 168 IBD patients (35.4%). A low BMD (T
      score<-1) was present in 64.3%. Osteoporosis (T-score<-2.5) was found in 23.8%.
      Low BMI, older age at the moment of diagnosis and male gender were found to be
      predictive factors of low BMD. For patients with osteoporosis, disease duration
      was an additional predictive factor. After subgroup analysis predictive factors
      were found to be the same in patients with Crohn's disease. CONCLUSIONS: The
      prevalence of osteopenia and osteoporosis in IBD patients in a regional centre is
      as high as the prevalence rates reported from tertiary referral centres. A low
      BMI, an older age at the moment of diagnosis and male gender were predictive
      factors of low BMD. Prediction of osteoporosis and osteopenia using risk factors
      identified in this and previous studies is presently not feasible.

PMID- 21172210
TI  - Reconsidering the methodology of "stress" research in inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: The goals of this paper are: 1) to critically review and
      analyze the methodology of the studies since 1990 linking stress to inflammatory
      bowel disease; and 2) to make recommendations for future research in this area of
      research. METHODS: Articles were restricted to empirical reports in the English
      language with human subjects. Eleven empirical articles were able to answer "How
      is psychological stress related to inflammation and/or the expression or course
      of inflammatory bowel disease?" RESULTS: Studies varied by choice of participant
      groups, method for classifying disease activity, choice of design, and definition
      and measurement of stress. Only half of the studies supported the hypothesis that
      stress affected IBD in some way. CONCLUSIONS: Current methodological limitations
      in the stress and gut inflammation research have made it difficult for us to
      ascertain the role of stress in inflammatory bowel disease. Authors provide a
      checklist of items to consider when designing future studies.

PMID- 21172213
TI  - The association of Haptoglobin polymorphism with Crohn's disease in Israel.
AB  - OBJECTIVES: Haptoglobin is a alpha(2)-sialoglycoprotein with hemoglobin binding
      capacity. Functional differences between the Hp phenotypes with the Hp 1-1
      protein being a superior anti-inflammatory to the Hp 2-2 protein have been
      identified. The aim of our study was to investigate the possible role of Hp
      polymorphism in the susceptibility to Crohn's disease and its clinical course.
      METHODS: Hp phenotypes were determined for 382 Israeli CD patients and 3243
      healthy controls. Phenotypic data for all Crohn's disease patients were carefully
      characterized. Analysis was preformed to evaluate the association between Hp
      polymorphism and Crohn's disease. RESULTS: The frequency of Haptoglobin 1-1 was
      lower in Crohn's disease patients than in healthy individuals (6.28% vs. 9.28%,
      P=0.057). There was no association between Haptoglobin phenotypes and disease
      location, behavior or extra-intestinal manifestations. No association was found
      between the Haptoglobin polymorphism and the frequency of the three Crohn's
      disease associated NOD2 mutations examined. CONCLUSIONS: We found a borderline
      significant decrease of the Haptoglobin 1-1 phenotype in Israeli Crohn's disease
      patients compared to healthy controls. Our findings may support the importance of
      inflammation in Crohn's disease pathogenesis and the protective function of
      Haptoglobin 1-1 in the susceptibility for Crohn's disease.

PMID- 21172214
TI  - Long-term outcome after infliximab for refractory ulcerative colitis.
AB  - BACKGROUND AND AIMS: Infliximab (IFX) has been shown efficacious for moderate-to
      severe ulcerative colitis (UC), but data on long-term efficacy are lacking. We
      investigated long-term outcome including colectomy rates in outpatients treated
      with IFX for refractory UC in a single referral centre, and evaluated if
      predictors could be identified. METHODS: The first 121 outpatients (median age
      38.0 years) with refractory UC treated with IFX were included. The primary
      outcome was colectomy-free survival. Secondary measures were sustained clinical
      response and serious adverse events. RESULTS: From the 81 patients (67%) with an
      initial clinical response to IFX, 68% had a sustained clinical response. No
      independent predictors of sustained clinical response could be identified. Over a
      median (IQR) follow-up period of 33.0 (17.0-49.8) months, 21 patients (17%) came
      to colectomy. Independent predictors of colectomy were absence of short-term
      clinical response [Hazard ratio 10.8 (95% CI 3.5-32.8), p<0.001], a baseline CRP
      level >=5 mg/L [Hazard ratio 14.5 (95% CI 2.0-108.6), p=0.006] and previous IV
      treatment with corticosteroids and/or cyclosporine [Hazard ratio 2.4 (95% CI 1.1
      5.9), p=0.033]. Six patients developed a serious infection, three a malignancy,
      two a post-operative complication and one patient died (suicide). CONCLUSIONS:
      With a median follow-up of 33.0 months after start of IFX, 17% of patients with
      refractory UC needed colectomy, while sustained clinical response was present in
      68% of initial responders.

PMID- 21172215
TI  - Communication of information to patients with inflammatory bowel disease: A
      European Collaborative Study in a multinational prospective inception cohort.
AB  - BACKGROUND AND AIMS: Communication to patients of information about their disease
      has become increasingly important in modern medicine, and particularly with
      chronic nonfatal disorders like inflammatory bowel disease (IBD), but the subject
      is not adequately researched or understood. METHODS: We studied the media and
      preferences for communication of information in a multi-national community-based
      inception cohort of European and Israeli patients with IBD and 10 years follow
      up, using structured questionnaires categorizing demographics, disease status,
      current and preferred sources of information, use of electronic media, role of
      patients' associations, and satisfaction level. RESULTS: The 917 patients
      completing the questionnaire were derived from northern (60%) and southern (40%)
      countries. The mean age was 48.3 years (62% under 50 years); 51% were males; 67%
      had ulcerative colitis, 33% Crohn's disease. Sixty-six percent of patients
      designated the specialist as their primary source of information, 77% indicated
      satisfaction with their current information, and 65% reported not receiving
      information about medical treatment in the past year. Patient concerns were about
      new research into their illness (64%), medical treatments (58%), risks and
      complications (51%) and genetics (42%). Preferred sources of information were
      paper bulletin (76%), electronic media (30%) and international organization
      (79%). Diagnosis (ulcerative colitis or Crohn's disease), gender, education level
      and country impacted significantly on patients' choices. CONCLUSIONS: In
      providing health care information to patients with IBD their individual attitudes
      and preferences must be considered. There should be greater roles for IBD
      patients' associations and international IBD-research organizations, and an
      increasing use of electronic media.

PMID- 21172216
TI  - Response pattern recognition in paediatric Crohn's disease patients treated with
      enteral nutrition.
AB  - AIM: To describe the response pattern to enteral nutrition (EN) in paediatric
      patients with moderately to severely active Crohn's disease (CD). MATERIAL AND
      METHODS: A previously described method for assessment of response pattern to
      various treatments for CD was used. Patients who received EN during the 10-year
      period 1995-2005 were prospectively registered. Patient data, clinical outcome,
      time to relapse and subsequent need for treatment were extracted from the files.
      Four weeks treatment with polymeric ready-to-use liquid formula was given. The
      clinical outcome was assessed by pattern recognition of the disease course 30
      days (immediate response) and 90 days (long-term response) after start of EN.
      RESULTS: Thirty-one patients (17/14 M/F), median age 14 years (range 7.5 -19.8
      years), received 46 courses of EN. Thirty-seven courses (80%) were completed.
      Immediate response: twenty-five courses (67%) led to complete response (CR), 8
      (22%) to partial response (PR) and in 4 courses (11%) no response (NR) was
      achieved. Long-term response: 21 courses (64%) led to prolonged response (PRO),
      defined as either maintenance of complete response (CR) or partial response (PR),
      while 12 courses (36%) were followed by loss of response (LR). The median time to
      relapse was 8.3 months (range 0.5-39 months). CONCLUSION: We found our model of
      response pattern to be a useful instrument for the description of results
      obtained during EN in children with CD.

PMID- 21172217
TI  - Idiopathic pancreatitis in inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: The incidence of pancreatitis is increased in inflammatory
      bowel disease. However, pancreatitis as an extraintestinal manifestation of the
      intestinal disease is exceedingly rare. We have retrospectively analyzed the
      prevalence of pancreatitis in a combined hospital cohort, and specifically
      studied cases in which no other cause than the intestinal disease itself could be
      found. METHODS: The prevalence of pancreatitis in 1057 inflammatory bowel disease
      patients from two hospitals in the Community of Madrid, Spain, was determined by
      means of database examination. RESULTS: The prevalence of pancreatitis was 2.74%
      (29 cases); only in four patients (0.38%) it was considered idiopathic and thus a
      possible extraintestinal manifestation. Underlying chronic pancreatitis was
      identified in three of these four patients. CONCLUSIONS: In inflammatory bowel
      disease patients, pancreatitis is more often due to a nonrelated cause, and cases
      that can be adscribed to extraintestinal manifestation of the intestinal disease
      are comparatively rare.

PMID- 21172218
TI  - Efficacy of Infliximab treatment in patients with severe Fistulizing Hidradenitis
      Suppurativa.
AB  - BACKGROUND: The association of Crohn's disease with Fistulizing Hidradenitis
      Suppurativa (FHS) was established in the 90s. FHS is a chronic disease,
      characterized by the formation of multiple abscesses and sinus tracts in apocrine
      gland-bearing areas. The aetiology and pathogenesis is unknown. The disease is
      painful and often socially disabling implying a poor Quality of Life. Treatment
      of FHS with Infliximab - a chimeric antibody to TNFalpha - has recently been
      proposed as alternative to surgery. AIM: To describe efficacy of Infliximab
      treatment in the first 2 Danish patients with resistant severe FHS. METHODS: Two
      patients with severe FHS previously unsuccessfully treated with conventional
      therapies. Infliximab 5 mg/kg was given as induction treatment. Clinical response
      was measured by MRI and modified Quality of Life scoring before and after the
      Infliximab. RESULTS: The first patient obtained partial remission after the first
      infusion, with 2 active sinus tracts of 20 detected by MRI. The patient became
      INF dependent and continued on maintenance treatment every 8th week. In total 8
      infusions. The second patient obtained partial remission after 3 infusions and
      did not experience relapse after withdrawal of Infliximab. The clinical findings
      of remission were underscored by showing improvement on MRI. The Quality of Life
      has been increased in both patients. CONCLUSION: Infliximab treatment seems to be
      efficacious in patients with severe FHS. Maintenance treatment may be necessary.
      Infliximab can lead to improvement in Quality of Life, partial remission of
      disease verified by closure of fistula in MRI and keeping the patients from
      mutilating surgery.

PMID- 21172219
TI  - Microcarcinoids associated with diversion colitis in a patient with Crohn's
      disease.
AB  - Diversion colitis is an iatrogenic disorder related to surgical diversion of the
      faecal stream from the colorectal mucosa, first described by Morson in 1972.
      Inflammation of the defunctioned mucosa seems to be related to deprivation of
      luminal nutrients, in particular short chain fatty acids. Histologic
      abnormalities include damage of the epithelium and reparative changes with crypt
      distortion and branching, a mixed acute and chronic inflammatory infiltrate with
      crypt abscesses and lymphoid hyperplasia, Paneth cell metaplasia and thickening
      of the muscularis mucosae. We report a case of diversion colitis in a 51-year-old
      female with Crohn's disease with multiple submucosal microcarcinoids in the
      rectal stump 17 years after diversion and discuss the hypothesis that
      hyperplastic and neoplastic lesions of neuroendocrine cells can result from
      proliferative response to chronic inflammation and repair, as well as epithelial
      neoplasms.

PMID- 21172220
TI  - Role of the T-cell interferon-gamma release assays in preventing reactivation of
      latent tuberculosis infection in immunosuppressed patients in treatment with anti
      TNF agents.

PMID- 21172221
TI  - Pathogenic Escherichia coli in inflammatory bowel diseases Proceedings of the 1st
      International Meeting on E. coli and IBD, June 2007, Lille, France.
AB  - Several different groups have recently reported the presence of pathogenic E.
      coli associated with ileal and/or colonic mucosa of patients with inflammatory
      bowel diseases. Given the important role of the gut microflora and
      enteropathogens in the initiation and perpetuation of intestinal inflammation,
      important issues now arise. Are these IBD associated E. coli pathogenic? Have
      they evolved from commensal bacteria? What is their reservoir? Are these bacteria
      sufficient to drive IBD pathogenesis? Which immunological defects may predispose
      to colonization by such bacteria? In June 2007, clinicians and basic scientists
      met in Lille, France with the goal of exchanging ideas and materials on this
      emerging topic. State-of-the-art lectures given by widely recognized
      international experts were associated with debates, case discussions and expert
      opinions. This paper summarizes most data that were exchanged during this day and
      represents an update on the potential role of pathogenic E. coli in inflammatory
      bowel diseases.

PMID- 21172222
TI  - Historical evolution of the management of severe ulcerative colitis.
AB  - Ulcerative colitis was first described in 1859, but it was not until the early
      20th century that it became a well recognized clinical entity. The patients of
      the old series showed high mortality rate ranging from 30% in the severe forms to
      60% in the fulminating forms. The introduction of corticosteroids in the 1950s
      dramatically improved the prognosis of patients with severe ulcerative colitis.
      The strategy based on intensive medical treatment, early detection of risk
      factors and early surgery progressively reduced the mortality rate to less than
      1%. Tachycardia, fever, reduced number of intestinal sounds, hypoalbuminaemia,
      hypokalaemia metabolic alkalosis and elevated C-reactive protein were recognized
      to be the most useful risk factors. Plain abdominal X-ray remains the very
      reliable suitable tool to detect early complications of severe colitis. Once
      reduced the mortality near to zero, treatment has been addressed to avoid
      colectomy. Cyclosporine and Infliximab are currently used as rescue therapy,
      however, despite the high remission rates achieved with both drugs, about 50% of
      the treated patients ultimately will come to colectomy over the next few years.

PMID- 21172223
TI  - Bowel sonography in occlusive Crohn's disease.

PMID- 21172224
TI  - Infliximab use in a patient with ulcerative colitis and alcoholic cirrhosis with
      portal hypertension.

PMID- 21172225
TI  - Intestinal fibrosis in inflammatory bowel disease - Current knowledge and future
      perspectives.
AB  - BACKGROUND AND AIMS: Intestinal fibrosis is a common complication of IBD that can
      become seriously symptomatic and may require surgical intervention if stricture
      formation ensues. This review discusses existing and developing knowledge of
      intestinal fibrosis and its implications for therapy. METHODS: Review of the
      literature, personal communications, unpublished observations. RESULTS: Known
      mechanisms of intestinal fibrosis include fibroblast proliferation and migration,
      activation of stellate cells, and extraintestinal fibroblast recruitment.
      However, novel mechanisms are being uncovered, including epithelial-to
      mesenchymal transition, endothelial-to-mesenchymal transition, pericyte
      differentiation, and fibrocyte recruitment. Most of the traditional and novel
      mechanisms underlying intestinal fibrosis are associated to the presence of
      chronic inflammation, but is also possible that fibrosis develops independently
      of persistent immune activation in the gut. At the moment, the development of
      preventive, non-interventional, and more effective management of intestinal
      fibrosis is hampered by the lack of a greater knowledge of its basic
      pathophysiology and predisposing factors. CONCLUSIONS: It is reasonable to expect
      that therapy of IBD-associated fibrosis will radically improve once the
      underlying mechanisms are better understood, and therapeutic modalities will
      emerge that prevent or reverse this complication of IBD.

PMID- 21172226
TI  - Th17 immune response in IBD: A new pathogenic mechanism.
AB  - Although traditionally associated with exaggerated Th1 or Th2 cell response, the
      gut inflammation occurring in patients with IBD is also characterized by
      production of cytokines made by a distinct lineage of T helper cells, termed Th17
      cells. The discovery that this new inflammatory T-cell subset drives immune
      mediated pathology and that the antigen-presenting cell-derived IL-23 is
      necessary for amplifying Th17 cell-associated inflammation has contributed to
      elucidate new pathways of intestinal tissue damage as well as to open new avenues
      for development of therapeutic strategies in IBD. In this review, we discuss the
      available data regarding the involvement of Th17 cells and their interplay with
      other mucosal cell types in the modulation of intestinal tissue inflammation.

PMID- 21172227
TI  - An experimental study on ulcerative colitis as a potential target for probiotic
      therapy by Lactobacillus acidophilus with or without "olsalazine".
AB  - Traditional medical treatments for ulcerative colitis (UC) are still compromised
      by its adverse effects and not potent enough to keep in remission for long-term
      periods. So, new therapies that are targeted at specific disease mechanisms have
      the potential to provide more effective and safe treatments for ulcerative
      colitis. Probiotics is recently introduced as a therapy for ulcerative colitis.
      In the present study, Lactobacillus acidophilus was selected as a probiotic
      therapy to investigate its effects in oxazolone-induced colitis model in rats
      that mimics the picture in human. The rats were grouped (8 rats each) as normal
      control group (Group I), Group II served as untreated oxazolone-induced colitis,
      Group III oxazolone-induced colitis treated with probiotic L. acidophilus
      (1*10(7) colony-forming units (CFU)/mL/day oral for 14 days), Group IV oxazolone
      induced colitis treated with olsalazine (60 mg/kg/day oral for 14 days), Group V
      oxazolone-induced colitis treated with probiotic L. acidophilus and olsalazine in
      the same doses and duration. Disease activity index (DAI) was recorded, serum
      levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and
      intrleukin-6 (IL-6) was assessed as inflammatory markers and the
      histopathological picture of the colon of each rat was studied. Disease activity
      index (DAI) showed significant positive correlation with the elevated serum
      levels of CRP (r=0.741, p<0.05), TNF-alpha (r=0.802, p<0.05) and IL-6 (r=0.801,
      p<0.05). Treatment with either L. acidophilus (group III) or olsalazine (group
      IV) resulted in significant reduction in serum levels of CRP, TNF-alpha and IL-6,
      as well as disease activity index (DAI). Treatment with combination of L.
      acidophilus and olsalazine (group V) offered more significant reduction in serum
      levels of CRP, TNF-alpha, IL-6 and disease activity index (DAI) when compared to
      either group II (untreated group), group III (treated with L. acidophilus) or
      group IV (treated with olsalazine). So, it was concluded that L. acidophilus
      probiotic could be recommended as adjuvant therapy in combination with olsalazine
      to achieve more effective treatment for ulcerative colitis. For application in
      human, this needs to be verified in further clinical studies.

PMID- 21172228
TI  - Occurrence of demyelinating diseases after anti-TNFalpha treatment of
      inflammatory bowel disease: A Danish Crohn Colitis Database study.
AB  - INTRODUCTION: It remains uncertain whether patients with inflammatory bowel
      disease (IBD) are at increased risk of developing demyelinating diseases,
      primarily multiple sclerosis (MS) and whether the introduction of biologic drugs
      in the treatment of IBD has altered this risk. AIM AND METHODS: The aim was to
      conduct a systematic review of literature on occurrence of demyelinating diseases
      in IBD patients, to assess a national Danish anti-TNFalpha treated IBD cohort in
      order to search for and describe the IBD cases with coexisting demyelinating
      diseases, and finally to compare the occurrence of MS in the anti-TNFalpha cohort
      to the occurrence in the general Danish population. A systematic MEDLINE
      literature search was conducted, medical files were scrutinized for
      identification and description of cohort patients with demyelinating disease, and
      risk of MS was calculated as a standardized morbidity ratio (SMR) using general
      population data for comparison. RESULTS: Four studies on the risk of
      demyelinating diseases in IBD were identified. One study revealed an observed
      prevalence of MS at onset of IBD at 3.7 times the expected (95% CI, 0.8-10.8). In
      the Danish anti-TNFalpha IBD cohort, 4 out of 651 patients developed
      demyelinating disorders after anti-TNFalpha treatment. The SMR for developing MS
      among Danish IBD patients treated with anti-TNFalpha was 4.2 (95% CI, 0.1-23.0).
      CONCLUSION: The literature review revealed an up to four-fold increased risk of
      demyelinating diseases, in particular MS, in IBD patients in general. The risk of
      developing MS in the anti-TNFalpha treated Danish cohort did apparently not
      exceed this risk.

PMID- 21172229
TI  - Microinflammation in patients with Crohn's disease in clinical remission.
AB  - BACKGROUND AND AIMS: It is not clear whether Crohn's disease patients in clinical
      remission (Crohn's disease activity index<150) display normal concentrations of
      inflammation sensitive biomarkers. Our goal in this work was to explore the
      intensity of the microinflammatory response in a group of Crohn's disease
      patients in clinical remission. METHODS: High sensitivity C-reactive protein,
      quantitative fibrinogen, erythrocyte sedimentation rate as well as platelet and
      leukocyte counts were examined in a group of 76 patients with Crohn's disease in
      remission and in 228 matched controls. RESULTS: Crohn's disease patients in
      clinical remission displayed a statistically significant (p<0.001) elevated
      concentration of hs-CRP (4.83+/-3.8 mg/l) compared to controls (1.05+/-2.9 mg/l).
      All other bio-markers were also significantly higher in Crohn's disease patients
      in remission compared to controls. Similar results were obtained in a subgroup of
      Crohn's disease patients with very low disease activity - CDAI<75. CONCLUSIONS:
      Clinical remission is not equivalent to biochemical remission raising a question
      concerning the true definition of remission in Crohn's disease.

PMID- 21172230
TI  - Lower doses of 6-mercaptopurine/azathioprine bring enough clinical efficacy and
      therapeutic concentration of erythrocyte 6-mercaptopurine metabolite in Japanese
      IBD patients.

PMID- 21172231
TI  - Is the efficacy of successful infliximab induction therapy maintained for one
      year lasting without retreatment in different behavior types of Crohn's disease?
AB  - The high cost of infliximab inhibits the regular retreatment of all patients in
      Hungary with Crohn's disease (CD) after beneficial induction therapy. This study
      is set out to evaluate the medium-term efficacy of induction therapy with
      infliximab without retreatment in CD patients with chronic activity and/or
      fistulae refractory to conventional therapy. METHODS: A retrospective 1-year
      review was undertaken of all CD patients with successfully induced remission or
      fistula closure with 3 infusions of infliximab. Infliximab was administered in a
      dose of 5 mg/kg 3 times, in weeks 0, 2 and 6. Clinical remission was defined as
      symptom resolution and an estimated Crohn's Disease Activity Index (CDAI) <150
      and complete fistula closure. We evaluated the clinical response, the estimated
      CDAI, the number of draining fistulae, the dosages of steroid and
      immunosuppressive drugs at 6 and 12 months after the last infusion, and the needs
      for hospitalization and surgical intervention during this period. Breslow
      (Generalized Wilcoxon) test was used as the statistical method. RESULTS: The data
      of the 50 patients (19 luminal, 31 fistulizing disease; average age 29. 3 [13-59]
      years, disease localization: 23 colon, 13 ileum, 13 ileocolon, 1 duodenum) were
      suitable for analysis. Infliximab induction therapy without retreatment resulted
      in a beneficial effect lasting for at least 1 year in 22 of the 50 patients
      (44%). 11 of the 19 patients (57.9%) with luminal disease remained in steroid
      free complete remission, while the fistulae persisted closed in only 11 of the 31
      patients (35.5%) (p<0.05). CONCLUSION: Infliximab induction therapy alone may
      result in sustained remission mainly in patients with luminal disease. These
      results suggest the need for maintenance therapy with infliximab after successful
      therapy induction in patients with fistulae, while luminal CD patients could
      possibly participate in regular retreatment only if needed. If these data are
      confirmed, this modification of the therapeutic procedure could well increase the
      cost-effectiveness of infliximab.

PMID- 21172232
TI  - The prevalence of hyper- and hypothyroidism in patients with ulcerative colitis.
AB  - BACKGROUND: The association between ulcerative colitis and thyroid disorders has
      been previously reported. However, most reports consist of single case
      description, and a systematic assessment of this relationship has only
      sporadically been investigated. AIMS: To study a cohort of patients with
      ulcerative colitis to establish the prevalence of hyper- and hypothyroidism.
      MATERIAL AND METHODS: During a four-year period, we studied thyroid function in
      162 ulcerative colitis patients (62 men, 100 women, age range 18-78 years).
      RESULTS: Thyroid dysfunction was present in 4 patients (2.5%) of the overall
      population and was represented by both hypo- (3 patients) and hyperthyroidism (1
      patient). The incidence of this kind of thyroid dysfunction was significantly
      (p=0.03) lower than that found in a large (more than 5000 subjects) control
      group. CONCLUSIONS: We conclude that the prevalence of hyper-/hypothyroidism is
      relatively low in patients with ulcerative colitis, at least in our country, and
      does not justify a systematic investigation of the thyroid function, except in
      selected cases, probably those with scarce or no response to standard therapeutic
      measures.

PMID- 21172233
TI  - Pneumonia due to Nocardia cyriacigeorgica in a patient with Crohn's disease
      treated with infliximab.
AB  - Infliximab, an anti-tumor necrosis factor alpha (TNF-alpha) antibody, is useful
      in the treatment of rheumatoid arthritis, Crohn's disease etc. It has been
      related to increases in the rate of several infections. We present the case of a
      53-year-old woman diagnosed with community-acquired pneumonia due to Nocardia
      cyriacigeorgica who was taking infliximab, azathioprine and prednisone for
      Crohn's disease.

PMID- 21172234
TI  - Concurrent diagnosis of Crohn's disease and colorectal carcinoma in a young man
      with abdominal pain.
AB  - The lead time between diagnosis of Crohn's disease and presentation with a
      Crohn's related malignancy is generally twenty years from diagnosis. This case
      outlines that of a young man who presented to the emergency department with
      abdominal pain and was subsequently discovered to have a malignant stricture
      complicating underlying Crohn's disease that was previously quiescent and
      undiagnosed. It demonstrates that a new diagnosis of Crohn's disease does not
      rule out previously quiescent underlying disease and therefore risk of colrectal
      carcinoma.

PMID- 21172235
TI  - Recurrent posterior scleritis and orbital myositis as extra-intestinal
      manifestations of Crohn's disease: Case report and systematic literature review.
AB  - BACKGROUND: Ocular episcleritis and uveitis are well-recognised extra-intestinal
      manifestations of Crohn's disease. Orbital myositis is rare: to our knowledge it
      has been associated with Crohn's disease in thirteen cases. Posterior scleritis,
      orbital myositis and Crohn's disease have been reported as coexisting in only two
      cases. METHODS AND RESULTS: We describe a third case, that of a 31-year old
      female with Crohn's colitis for 8 years, complicated by enteropathic arthritis
      and pyoderma gangrenosum. She presented with intense and intractable periorbital
      pain, particularly at night and worse on eye movements. B-scan ultrasonography
      confirmed posterior scleritis and treatment with high dose oral steroids (up to
      60 mg prednisolone) was initially effective, but subsequently failed to control
      the inflammation. There was only a partial response to infliximab. Five months
      after presentation, diplopia developed, with failure of abduction of the left
      eye. MRI scan of the orbits confirmed orbital myositis involving the left lateral
      and medial rectus muscles. Pulsed intravenous methylprednisolone and six cycles
      of intravenous cyclophosphamide over a three month period resulted in complete
      resolution of inflammatory symptoms. CONCLUSIONS: This case highlights a rare
      combination of ocular abnormality secondary to Crohn's disease and reports
      successful resolution with aggressive immunosuppressive therapy.

PMID- 21172236
TI  - Pitfalls and errors in the diagnosis of collagenous and lymphocytic colitis.
AB  - The diagnosis of both CC and LC is based on a compatible clinical picture and
      well-established objective histological criteria. The motivation degree of the
      involved physicians is essential in the diagnosis of microscopic colitis. The
      gastroenterologist should refer every patient with chronic watery diarrhea to
      perform a colonoscopy in spite of the benign course of the disease and the
      absence of alarm symptoms or signs. The endoscopist should take multiple stepwise
      biopsy samples of the colonic mucosa despite that the mucosa looked
      macroscopically normal. Finally, the pathologist should be motivated to use
      objective histological criteria to make the diagnosis. In this context, it is
      important to define the terminology as clearly as possible to avoid confusion.

PMID- 21172237
TI  - Management of loss of response to anti-TNF drugs: Change the dose or change the
      drug?

PMID- 21172238
TI  - Why does Crohn's disease usually occur in terminal ileum?
AB  - Crohn's disease can affect any part of the gastrointestinal tract, but terminal
      ileum is the most frequent localization. The reason why Crohn's disease is
      primarily located in the distal part of the ileum remains unexplained. In this
      article it has been attempted to provide a compelling explanation why Crohn's
      disease usually occurs in terminal ileum. Recent data indicate that some
      individuals are genetically predisposed to develop ileal Crohn's disease. Two
      genetic alterations, the polymorphism of Caspase Associated Recruitment Domain
      (CARD15) and Carcinoembryonic Antigen-related Cell Adhesion Molecule 6 (CEACM6),
      favour the colonization of terminal ileum by entero adherent-invasive Escherichia
      coli (AIEC). The adhesion of these bacteria to epithelial intestinal cells
      depends on Carcinoembryonic Antigen-related Cell Adhesion Molecule 6 expression
      in ileal epithelial cells and on the reduced ileal defensins expressed in a
      CARD15 dependent manner. Genetic defects in Authophagy-related 16-like gene
      (ATG16L1) and Immunity-related Guanosine Triphospatase (IRGM) recently found in
      ileal CD patients lead to a reduction of bacterial killing by macrophages and
      consequent continuous immunological upstimulation, cytokine secretion, chronic
      inflammation of the ileum and tissue injury. On the basis of all these data
      Crohn's disease of the ileum seems to be a subset of the disease mainly
      genetically determined.

PMID- 21172239
TI  - Lack of efficacy of azathioprine in the treatment of axial arthritis complicating
      Crohn's disease.

PMID- 21172240
TI  - Talking about life and IBD: A paradigm for improving patient-physician
      communication.
AB  - Despite recent awareness and understanding of quality of life (QOL) issues in
      IBD, nearly half of physicians in Europe do not ask their IBD patients about
      their QOL and nearly half of patients do not initiate a conversation with their
      physicians about QOL, according to a recent survey by the European Federation of
      Crohn's and Colitis Associations (EFCCA) [S. Ghosh and R. Mitchell, Impact of
      inflammatory bowel disease on quality of life: results of the European Federation
      of Crohn's and Ulcerative Colitis Associations (EFCCA) patient survey. J Crohn's
      Colitis. 2007;1(1):10-20.]. Effective treatment has been shown to help improve
      QOL in Crohn's disease patients [E.V. Loftus, J.F. Colombel, R. Panaccione, et
      al, Adalimumab sustains qualify-of-life improvements in patients with Crohn's
      disease: 2-year data from CHARM [P078]. Poster abstract presented at ECCO 2008,
      Lyon, France., S.B. Hanauer, B.G. Feagan, G.R. Lichtenstein, et al, Maintenance
      infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet
      2002;359:1541-1549.], suggesting there is a need to improve physician-patient
      communication about QOL and new treatment options that may help. To address this
      need, a multidisciplinary European group initiated by EFCCA (including an IBD
      consultant, nurse specialist, an IBD patient and two IBD EFCCA
      representatives/carers) set out to describe the key aspects of an 'ideal' IBD
      consultation and main considerations when talking about the impact of IBD on
      patients' daily lives. These insights can serve as a framework for developing
      practical tools to help facilitate IBD patient-physician communication.

PMID- 21172241
TI  - Increasing incidence of Clostridium difficile-associated diarrhea in inflammatory
      bowel disease.
AB  - INTRODUCTION AND AIM: Over the last decade a rise in Clostridium difficile
      associated diarrhea (CDAD) has been observed. A higher incidence of CDAD has also
      been suggested in patients with inflammatory bowel disease (IBD), and may be a
      challenging factor in the differential diagnosis of flares. It is unclear if the
      increase is caused by the enhanced use of immunosuppressive therapy in IBD. We
      investigated if CDAD infection is increasing in IBD patients and evaluated
      outcome and possible predisposing factors. METHODS: Through an electronic
      database of the Laboratory of Microbiology of our hospital (tertiary referral
      center), all stool samples from patients admitted for diarrhea and hospitalized
      on gastroenterology wards between January 2000 and January 2008 were reviewed for
      diagnosis of CDAD. For analysis, we compared two periods of equal duration.
      RESULTS: A total of 57 patients were diagnosed with CDAD, of whom 26.3% had
      concomitant IBD. A 3.75-fold increase in CDAD was observed between period 1 and
      period 2, irrespective of underlying IBD and with a comparable total number of
      analyzed stool samples between both periods. Non-IBD patients were significantly
      older. Antibiotic use three months prior to the infection was higher in non-IBD
      (29/42 or 69%) than in IBD patients (6/15 or 42%) (p = 0.047). Nine IBD patients
      were on concomitant immunomodulators, and this was not different between period 1
      and period 2. Most patients had a successful outcome and only one patient with
      ulcerative colitis needed semi-urgent colectomy. Two patients died in the non-IBD
      group. The duration of hospital stay was significantly lower in IBD patients.
      CONCLUSION: We observed a significant rise in CDAD in both IBD and non-IBD. The
      clinical outcome was favorable with only one IBD patient needing semi-urgent
      colectomy. Because C. difficile can mimic an IBD flare, it is essential that
      clinicians are vigilant to this complication. The use of immunosuppressive drugs
      in IBD does not influence the risk.

PMID- 21172242
TI  - Reduction of dietary poorly absorbed short-chain carbohydrates (FODMAPs) improves
      abdominal symptoms in patients with inflammatory bowel disease-a pilot study.
AB  - OBJECTIVE: Functional gut symptoms are common in patients with inflammatory bowel
      disease (IBD). Since poorly absorbed, short-chain carbohydrates (FODMAPs) appear
      to play an important role in the induction of functional gut symptoms, we aimed
      to determine the effect of their dietary restriction on abdominal symptoms in
      patients with stable IBD and to examine factors associated with success of and
      adherence to the diet. MATERIAL AND METHOD: 52 consecutive patients with Crohn's
      disease and 20 with ulcerative colitis who received dietary advice at least 3
      months prior at a gastrointestinal dietetic service in Victoria, Australia,
      underwent a retrospective telephone questionnaire. Information gathered included
      patient demographics, recall of dietary advice, dietary adherence, and change in
      gastrointestinal symptoms. RESULTS: Up to 70% of patients were adherent to the
      diet. Approximately one in two patients responded (defined as improvement of at
      least 5 out of 10 in overall symptoms). Overall abdominal symptoms, abdominal
      pain, bloating, wind and diarrhoea improved in patients with Crohn's disease and
      ulcerative colitis (p<0.02 for all), but constipation did not. For Crohn's
      disease, efficacy was associated with dietary adherence (p= 0.033) and inefficacy
      with non-adherence (p=0.013). Sustained response was associated with post
      secondary education and working 35 h per week or less (p<0.03). CONCLUSIONS:
      These data suggest that reduction of FODMAP intake offers an efficacious strategy
      for patients with IBD who have concurrent functional gut symptoms. A controlled
      dietary intervention trial is indicated.

PMID- 21172244
TI  - Perception of improved state of health and subjective quality of life in Crohn's
      disease patients treated with Infliximab.
AB  - BACKGROUND AND AIMS AND METHOD: Although Infliximab is a very potent therapy of
      refractory Crohn's disease, its administration requires iterative infusions in
      hospital and there are concerns regarding its long-term safety. The aim of this
      study was to assess in a sample of 51 patients suffering from CD the impact of
      type of treatment (intravenous Infliximab versus conventional therapy without
      Infliximab) on the evaluation of the state of health (CGI) and the quality of
      life (MOS-SF36). Secondary variables were also assessed: the impact of depression
      (MADRS), the impact of activity of the disease (Harvey-Bradshaw Index). RESULTS:
      Overall, the assessments made using the CGI and the SF-36 revealed that the two
      types of treatment did not differ on the assessment of state of health and
      quality of life. A downward influence of depression and activity of the disease
      was observed. CONCLUSION: Patients considered more efficacy of Infliximab than
      its potential side effects. It seems important to assess and to consider
      depression in order to improve medical care setting of Crohn's disease.

PMID- 21172243
TI  - Potential role of protease-activated receptor-2-stimulated activation of
      cytosolic phospholipase A(2) in intestinal myofibroblast proliferation:
      Implications for stricture formation in Crohn's disease.
AB  - BACKGROUND AND AIMS: Myofibroblast hyperplasia contributes to muscularis mucosae
      thickening and stricture formation in Crohn's disease (CD). Protease-activated
      receptor-2 (PAR-2) and cytosolic phospholipase A(2) (cPLA(2)) are known
      regulators of cell growth, but their significance in intestinal myofibroblast
      proliferation remain to be elucidated. The principle aims of the present study
      were to investigate if PAR-2 is expressed in the expanded muscularis mucosa in
      ileal CD specimens, if inflammatory cytokines may stimulate PAR-2 expression in
      intestinal myofibroblasts, and if PAR-2 and cPLA(2) may regulate intestinal
      myofibroblast growth. METHODS: Immunohistochemistry was used for detection of PAR
      2 in ileal CD specimens. Studies on PAR-2 expression, PLA(2) activation and cell
      growth were performed in a human intestinal myofibroblast cell line, CCD-18Co.
      PAR-2 expression was investigated by RT-PCR and immunocytochemistry. PLA(2)
      activity was analyzed by quantification of released (14)C-arachidonic acid ((14)C
      AA). Cell growth was examined by (3)H-thymidine incorporation and cell counting.
      RESULTS: The thickened muscularis mucosae of the CD specimens showed strong PAR-2
      expression. In cultured myofibroblasts, tumor necrosis factor-alpha (TNF-alpha)
      up-regulated PAR-2 mRNA and protein, and potentiated PAR-2-stimulated (14)C-AA
      release by two known PAR-2 activators, trypsin and SLIGRL-NH(2). The release of
      (14)C-AA was dependent on cPLA(2). Trypsin stimulated the proliferation of serum
      starved cells, and inhibition of cPLA(2) reduced normal cell growth and abolished
      the growth-promoting effect of trypsin. CONCLUSIONS: The results suggest that PAR
      2-mediated cPLA(2) activation might be of importance in intestinal myofibroblast
      proliferation. The results also point to the possibility that PAR-2 up-regulation
      by inflammatory cytokines, like TNF-alpha, may modulate this effect.

PMID- 21172245
TI  - An economic evaluation comparing once daily with twice daily mesalazine for
      maintaining remission based on results from a randomised controlled clinical
      trial.
AB  - BACKGROUND AND AIMS: Standard practice to maintain remission in ulcerative
      colitis (UC) consists of daily mesalazine therapy. However, frequent dosing is
      associated with poor adherence and increased failure rates. The PODIUM (PentasaTM
      Once Daily In UC Maintenance) randomised control trial showed 2 g once daily (OD)
      to be superior to twice daily (BD) dosing for maintaining remission. We sought to
      determine whether this alternative dosing regimen is cost-effective. METHODS: An
      economic evaluation was conducted to compare costs and outcomes of OD with twice
      daily (BD) dosing. The main outcome considered was quality-adjusted life years
      (QALYs) based on health state utilities derived from the primary outcome measure,
      remission without relapse at 12 months defined by a UCDAI score <=1. The economic
      evaluation consisted of two health states: (1) remission and (2) active UC.
      RESULTS: Annual average treatment costs for OD and BD dosing were L654 (95% CI:
      L536-L759) and L747 (L620-L860), respectively with an average per person savings
      of L93 per year. Average annual costs of ancillary care for relapse for OD and BD
      dosing were L307 (L241-L383) and L396 (L320-L483), respectively. Treatment with
      OD 2 g mesalazine resulted in an incremental QALY improvement of 0.004 units,
      indicating that it was the dominant treatment option (i.e. improved outcomes and
      cost-saving). Variations in parameter estimates in the sensitivity analysis
      indicated that mesalazine had >0.95 probability of being cost-effective compared
      to BD based on accepted willingness to pay thresholds applied by the UK National
      Health Service. CONCLUSIONS: Once daily 2 g mesalazine for maintaining remission
      in UC is cost-saving compared with 1 g twice daily. Cost-savings with 2 g once
      daily were achieved by differences in ancillary care attributed to higher failure
      rates observed with 1 g twice daily.

PMID- 21172246
TI  - Non-toxic megacolon due to transverse and sigmoid colon volvulus in a patient
      with ulcerative colitis.
AB  - Intestinal volvulus in patients with inflammatory bowel disease is rare. A 83
      year-old woman diagnosed with ulcerative colitis five years ago was referred to
      our hospital due to abdominal distension. The patient had been diagnosed with
      pancolitis and dolichocolon and was started on mesalazine 1.5 g/day treatment
      resulting in long-term remission. Physical examination showed abdominal
      distention with no rebound; however on auscultation abdominal sounds were absent.
      Patient had no signs of toxicity. Temperature was 38.2  degrees C, heart rate was
      82 bpm and respirations were 16/min. Laboratory investigation showed elevated
      white blood cell count (20,000/mm(3)) with hemoglobin at 13.2 g/dl and C-reactive
      protein at 310 mg/dl. Radiology was suggestive of megacolon and volvulus. Patient
      underwent endoscopy, which revealed normal rectal mucosa; there were however
      present areas of bowel gangrene. Urgent laparotomy was performed which revealed
      double transverse and sigmoid colon volvulus. A left hemicolectomy and
      transversectomy were performed. A case of a patient with ulcerative colitis is
      being presented here, exhibiting a non-toxic megacolon, resulting from a double
      transverse and sigmoid volvulus probably stemming from congenital dolichocolon.
      This case is stressing the importance of prompt differential diagnosis in such
      cases of megacolon as any symptom misinterpretation may result in unfavorable
      outcomes.

PMID- 21172247
TI  - First endoscopic appearance of ulcerative colitis.

PMID- 21172248
TI  - Infliximab and refractory ulcerative colitis.

PMID- 21172249
TI  - Reply to Dr. Caprilli et al.'s letter.

PMID- 21172250
TI  - European evidence-based Consensus on the prevention, diagnosis and management of
      opportunistic infections in inflammatory bowel disease.

PMID- 21172251
TI  - Familial aggregation in Crohn's disease and ulcerative colitis in a Norwegian
      population-based cohort followed for ten years.
AB  - BACKGROUND AND AIMS: To explore the change in risk among 1st degree relatives of
      ulcerative colitis (UC) and Crohn's disease (CD) for development of concordant
      disease in an incidence cohort followed for ten years. Furthermore, we wanted to
      compare familial and sporadic cases regarding clinical characteristics and the
      course of the disease. METHODS: This population-based study included 421 patients
      with UC and 197 with CD enrolled from 1990 to 1994. Clinical characteristics and
      the number of 1st degree relatives of the patients were recorded continuously
      during ten years. RESULTS: Age at diagnosis in CD patients (OR=0.95, 95% CI: 0.93
      0.98) and cumulative relapse rate in UC patients (OR=4.91, 95% CI=1.16, 20.75)
      were significantly associated to familial clustering. Based on the calculated
      population prevalence of CD (262/100000) and UC (505/100000), the age-adjusted
      risk for development of concordant disease was 25.9 and 8.6 among siblings and
      parents of CD, respectively. In UC, the corresponding risks were 8.6 and 1.5. In
      the course of ten years the increase in risk was observed only among siblings
      (28%) and parents (97%) of UC, in contrast to no increase in CD. Moreover, the
      concordance for UC was high in three generations. CONCLUSIONS: Our study
      confirmed the importance of genetic influence on the development of CD. Within an
      observation period of ten years, the increased concordance and relapse rate in
      familial UC, might point to a larger genetic component in UC than previously
      suggested.

PMID- 21172252
TI  - Increased expression of protease-activated receptor-2 in mucosal mast cells in
      Crohn's ileitis.
AB  - BACKGROUND AND AIMS: Activation of protease-activated receptor-2 (PAR-2) may
      stimulate various events of importance in inflammatory processes, including
      release of inflammatory mast cell mediators. PAR-2 is frequently up-regulated
      during inflammatory conditions, but it is not known if the expression is altered
      in Crohn's disease. The aim of the present study was to investigate the ileal
      mucosal PAR-2 expression in Crohn's ileitis, with particular emphasis on the
      expression in ileal mucosal mast cells. METHODS: Surgical specimens from the
      distal ileum were collected from patients with Crohn's ileitis and patients with
      colonic cancer as controls. The overall expression of PAR-2 was investigated by
      Western blot, and the presence of PAR-2 expressing mucosal mast cells by
      immunohistochemistry and cell counting. The effect of tumor necrosis factor-alpha
      (TNF-alpha) on the PAR-2 expression in a human mast cell line (HMC-1) was
      investigated by RT-PCR and immunocytochemistry. RESULTS: In Crohn's specimens,
      the fraction of PAR-2-expressing mucosal mast cells was increased about 2.5 times
      (P<0.001; n=14) compared with specimens from control patients (n=6). No
      difference was found between inflamed (n=6) and uninflamed Crohn's specimens
      (P>0.05; n=8). Exposure to TNF-alpha for 48 h up-regulated PAR-2 mRNA and protein
      expression in the HMC-1 cell line. CONCLUSION: PAR-2 is up-regulated on ileal
      mucosal mast cells in Crohn's ileitis, possibly due to the action of inflammatory
      cytokines, such as TNF-alpha. This may contribute to perpetuating the
      inflammatory process in the intestinal mucosa in Crohn's ileitis.

PMID- 21172253
TI  - Long-term prevention of post-operative recurrence in Crohn's disease cannot be
      affected by mesalazine.
AB  - BACKGROUND: Prevention of post-operative recurrence has a central role in the
      management of Crohn's Disease (CD). Many drugs have been evaluated in prospective
      randomised controlled trials (RCTs) but the results are disappointing.
      Mesalazine, the drug more extensively investigated, has been shown to be
      effective for preventing recurrence in the short-term; however, the overall
      benefit is small and no data are available on the long-term effectiveness. AIM:
      To compare the long-term occurrence of post-operative recurrence in patients who
      received regular prophylactic treatment with mesalazine with patients who did not
      receive prophylaxis after the first radical resection for ileo-caecal CD.
      PATIENTS AND METHODS: The records of 216 patients with ileo-caecal CD at their
      first resection were reviewed: 146 patients (67.6%) received post-operative
      prophylaxis with mesalazine while 70 patients (32.4%) received no prophylaxis.
      Allocation of patients in the two groups was determined by patients' preferences
      and by different policies in the post-operative prophylactic approach. The mean
      follow-up after surgery was 153.7 months (range 12-544). The co-primary endpoints
      were post-operative clinical and surgical recurrence. STATISTICAL ANALYSIS:
      Kaplan-Meier survival method, Chi-square, Student t-test. RESULTS: The two groups
      were comparable with regard to gender, age at surgery, smoking habits, pattern of
      CD (perforating/not perforating), and disease duration before surgery. One year
      after surgery, a small, not statistically significant, risk reduction in clinical
      recurrence was observed in mesalazine treated group (-7.6%; 95% CI -18.0% to
      2.8%). Within 10 years after surgery, the cumulative probability of clinical
      recurrence and surgical recurrence were similar in the two groups (Log Rank test
      p=0.9 and p=0.1 respectively). CONCLUSION: Mesalazine prophylaxis is not
      effective for preventing the long-term post-operative recurrence in ileo-caecal
      Crohn's disease.

PMID- 21172254
TI  - Inflammatory Bowel Disease in South Limburg (the Netherlands) 1991-2002:
      Incidence, diagnostic delay, and seasonal variations in onset of symptoms.
AB  - BACKGROUND AND AIMS: Increasing incidence in Inflammatory Bowel Disease (IBD) has
      been suggested. Recent data on population based incidence rates within Europe are
      however scarce. Primary aim was to investigate prospectively the incidence of IBD
      within a well-defined geographical and administrative area of the Netherlands,
      the South Limburg IBD registry. Secondary aims were to study the duration of
      symptoms before diagnosis (lag time) and seasonal influences on the incidence of
      IBD. METHODS: The incidence was examined using standardized registration of all
      newly diagnosed IBD patients, between 1-1-1991 and 1-1-2003. Medical records were
      reviewed to verify the diagnosis. At inclusion, diagnostic lag time was
      registered in months. RESULTS: Age standardized incidence rates per 100,000
      person-years (p-y) were: Crohn's Disease, male 4.84, female 7.58; Ulcerative
      Colitis, male 8.51, female 6.92; and Indeterminate Colitis, male 1.05, female
      0.93. Incidence rates did not significantly changes over time in either Crohn's
      Disease, Ulcerative Colitis or Indeterminate Colitis. Lag time was 5 (0-360)
      months in Crohn's Disease, 3.0 (0-480) months in Ulcerative Colitis and 3.0 (0
      180) months in Indeterminate Colitis. Lag time was not significantly different
      between the periods 1991-1993 and 2000-2002, and no statistical differences in
      the onset of symptoms per calendar month or season were found. CONCLUSIONS: Our
      results, from the South Limburg region (the Netherlands), show no significant
      change in incidence rates of IBD. The incidence found is relatively high compared
      to other European countries. Lag time did not change during the study period, and
      seasonal influence of incidence rates could not be confirmed.

PMID- 21172255
TI  - Familial cases of glomerulonephritis complicating Crohn's disease.
AB  - A part from nephrolithiasis, renal involvement is rare in the course of Crohn's
      disease, particularly glomerulonephritis. On the other hand, while onset of
      Crohn's disease is strongly influenced by environmental and genetic factors,
      little is known regarding influence of these factors on extra intestinal
      manifestations. We report a familial case of glomerulonephritis that occurred in
      a 38-year old woman and her mother, 59 years old with a 7-year and a 37 year
      history of stenosing ileocolonic disease, respectively. Both of them developed
      peripheral oedema with nephrotic syndrome during the course of their Crohn's
      disease while they had no intestinal symptoms and were not receiving any
      maintenance therapy. Renal function was conserved in the former while the latter
      developed renal failure and had already small size kidneys on abdominal
      sonography. Thus, renal biopsy had been performed only in the former patient and
      had showed membranous glomerulonephritis. Investigations showed no other
      underlying disease than Crohn's disease. Through this report we emphasis possible
      genetic influence on extra intestinal manifestations, particularly
      glomerulonephritis, in Crohn's disease patients.

PMID- 21172256
TI  - Safe 6-thioguanine therapy of a TPMT deficient Crohn's disease patient by using
      therapeutic drug monitoring.
AB  - The immunosuppressive thiopurines, azathioprine (AZA) and 6-mercaptopurine (6
      MP), have proven efficacy in steroid-dependant or refractory inflammatory bowel
      disease (IBD). In case of TPMT deficiency serious myelosuppression may occur. 6
      thioguanine (6-TG), has been suggested in case of AZA and 6-MP resistant or
      intolerant patients. Our case demonstrates that very low dose 6-TG under close
      clinical surveillance and frequent therapeutic drug monitoring, may be a rescue
      drug for IBD-patients with low or without functional TPMT activity.

PMID- 21172257
TI  - Retrobulbar optic neuritis associated with infliximab in a patient with Crohn's
      disease.
AB  - BACKGROUND AND AIM: : Infliximab is a chimeric human-murine monoclonal antibody
      with a high affinity and specificity for tumor necrosis factor alpha, which is
      nowadays widely used in Crohn's disease. An exacerbation of demyelinating disease
      as an adverse effect of this treatment is rare. The aim of this study was to
      discuss the relationship between infliximab and optic neuritis. CASE REPORT: : We
      describe a 55-year old man with Crohn's disease who developed retrobulbar optic
      neuritis of the left eye after the infusion of infliximab. The outcome was
      favorable after systemic steroid treatment. CONCLUSION: : Although the
      relationship between the onset of visual symptoms and the infusion of infliximab
      may have been coincidental, we believe that this case report underscores the
      clinical awareness of the possible association, especially in light of the
      increasing use of this cytokine inhibitor.

PMID- 21172258
TI  - Autoimmune hemolytic anemia in a young adult with Crohn's disease and primary
      sclerosing cholangitis: An unusual association.

PMID- 21172259
TI  - Can meat and protein really increase, while vegetables and fruits decrease the
      risk of inflammatory bowel disease? How?

PMID- 21172260
TI  - Diagnosis of Clostridium difficile-associated diarrhea.

PMID- 21172261
TI  - Severe esophageal Crohn's disease: Healing of lesions after 1 week therapy with
      infliximab.

PMID- 21172262
TI  - The role of CMV in steroid-resistant ulcerative colitis: A systematic review.
AB  - BACKGROUND AND AIMS: Steroid-resistance presents a management challenge in
      ulcerative colitis. How steroid-resistance occurs is unknown, but cytomegalovirus
      infection, often unrecognised, may be the cause in some patients. Current
      evidence and therapeutic recommendations are examined. METHODS: A systematic
      review of PubMed and EMBASE databases was performed. Search and exclusion
      criteria are defined in the text. RESULTS: Heterogeneity of experimental design
      and definitions of key terms were notable. Criteria for cytomegalovirus disease,
      infection or detection varied, as did definitions of steroid-resistance. CMV
      infection defined by antigenaemia or serology was common in patients on steroids
      and associated with a higher rate of steroid-resistance (41.66-61% versus 0-68%
      in steroid-responsive patients). Colonic mucosal cytomegalovirus disease detected
      by histopathology was associated with intravenous steroid-resistance in 5-36%,
      compared to 0-10% of steroid-responsive patients. CMV colitis has rarely been
      reported in association with ulcerative colitis without steroids or other
      immunomodulators. CMV colitis in healthy individuals is so exceptional as to be
      the topic of case reports. CONCLUSION: Ulcerative colitis and its treatment put
      patients at risk of CMV infection or reactivation. A distinction is necessary
      between CMV disease (colitis) and CMV infection. Only colonic mucosal CMV
      infection detected by histopathology appears clinically relevant and appropriate
      for antiviral therapy. CMV antigenaemia may be associated with steroid
      resistance, but may also be a self-limiting marker of viral reactivation. The
      impact of CMV on steroid-resistance is complicated by inconsistencies in the
      literature. Coherent definitions of clinically relevant CMV infection and steroid
      resistance are needed.

PMID- 21172263
TI  - The long journey of salicylates in ulcerative colitis: The past and the future.
AB  - The advent of salicylates in the treatment of ulcerative colitis started in 1938
      with the discovery of Salazopyrin by Nanna Svartz. This drug offered for the
      first time a therapeutic chance to patients with ulcerative colitis. In this
      paper we describe the fascinating history of Salazopyrin and salicylates from the
      first serendipitous observations to the last randomized clinical trials.
      Attention was paid to the pharmacokinetics and the mechanism of action of 5
      aminosalicylates and, in particular, to the issue of the mucosal concentrations
      of 5-aminosalicylates and its therapeutic efficacy. Moreover a look at the new
      oral mesalazine formulations that allow the homogenous distribution of 5
      aminosalicylate through all the large bowel was taken. Lastly, the possible use
      of mesalazine in the prevention of colorectal cancer was reviewed.

PMID- 21172264
TI  - Public awareness of Crohn's disease and ulcerative colitis: A national survey.
AB  - BACKGROUND AND AIMS: Crohn's disease (CD) and ulcerative colitis (UC) are
      lifelong inflammatory bowel diseases (IBD) progressing over time. Lack of public
      awareness may contribute to tardy consultation of primary care physicians, late
      diagnosis and development of potentially preventable complications of disease. A
      public opinion poll has been performed to assess the awareness of CD and UC in
      the Austrian population. METHODS: In March/April 2006, 122 interviewers of an
      international polling institute asked 1001 Austrians aged 16 and over about their
      knowledge of CD and UC. People interviewed were selected using a quota sampling
      scheme representing the Austrian population. RESULTS: CD and UC were never
      heard/read in 68% and 79% (group 1), respectively, whereas 23% and 14% had
      already heard/read these terms (group 2). Only 9% and 7% of participants gained
      information on or were familiar with CD and UC (group3), respectively. Among
      provided choices of potentially afflicted organs interviewees of group 3
      associated the terms "CD" and "UC" with an intestinal disease in 86% each. Among
      those of group 2+3 the corresponding figures were 53% and 60% for CD and UC,
      respectively. Overall, 7% and 4% of the participants stated to be aware and/or
      informed on CD and UC and correctly associated these terms with an intestinal
      disease. CONCLUSIONS: This is the first study on public awareness of the terms
      "Crohn's disease" and "ulcerative colitis". Poor knowledge in the public is
      reported which may vastly impact outcome and health economic consequences of IBD.

PMID- 21172265
TI  - Long term efficacy and safety of allopurinol and azathioprine or 6-mercaptopurine
      in patients with inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: We previously reported that IBD patients who are non
      responders to thiopurines with preferential shunting of metabolites to
      hepatotoxic 6-methylmercaptopurine ribonucleotides compared to 6-thioguanine
      nucleotides can reverse the ratio of 6-MMP/6-TGN and respond to thiopurines with
      the addition of allopurinol. The objective of this study is to report long term
      efficacy and safety, along with results for an additional 11 patients. METHODS:
      Retrospective chart review of patients at the University of Chicago IBD Center
      treated with allopurinol in addition to thiopurines. RESULTS: Twenty five
      patients with Crohn's disease or ulcerative colitis were enrolled. Within the
      first month of therapy 6-TGN metabolite levels increased from a mean of 186.5+/
      17.4 (SE) to 352.8+/-37.8 pmol/8*10(8) (p=0.0001). Over the same period 6-MMP
      levels decreased from a mean of 11,966+/-1697 to 2004+/-536 pmol/8*10(8)
      (p<0.0001). The mean daily dosage of prednisone decreased from 19.8+/-3.8 mg to
      5.3+/-2.7 mg (p=0.03). Thirteen patients have a minimum of one year follow-up.
      Nine of these thirteen patients have continued on therapy for at least 2 years.
      All thirteen of these patients continue to be in clinical remission at the last
      follow-up visit. No patients have had evidence of sustained thrombocytopenia or
      abnormal liver enzymes. CONCLUSIONS: In AZA/6-MP non-responders with increased 6
      MMP/6-TGN ratios, addition of allopurinol continues to demonstrate safety and
      efficacy for long-term maintenance and steroid-sparing in IBD.

PMID- 21172266
TI  - An economic evaluation comparing concomitant oral and topical mesalazine versus
      oral mesalazine alone in mild-to-moderately active ulcerative colitis based on
      results from randomised controlled trial.
AB  - INTRODUCTION: A previous randomised controlled trial has demonstrated that oral
      plus topical mesalazine enema is more effective than oral mesalazine alone for
      achieving clinical remission in mild-to-moderately active extensive ulcerative
      colitis (UC). To evaluate whether this strategy is cost-effective we conducted an
      economic evaluation comparing 1 g topical mesalazine in combination with 4 g oral
      mesalazine compared to 4 g mesalazine monotherapy in mild-to-moderately active
      UC. METHODS: The economic evaluation was based on the ability to achieve
      remission using changes from baseline in the ulcerative colitis disease activity
      instrument (UCDAI). A cost-utility analysis was used where the main outcome was
      quality-adjusted life years to reflect improved quality of life associated with
      achieving remission compared with active disease. A simulated Markov model with
      five health states was constructed to model cost and outcome changes over time:
      (1) active UC; (2) mesalazine-refractory active UC; (3) steroid-refractory active
      UC; (4) infliximab-responsive active UC; and (5) remission. To reflect parameter
      uncertainty in the cost-effectiveness analysis probabilistic sensitivity analysis
      (PSA) was conducted by varying relevant clinical parameters. RESULTS: Average
      treatment costs required to transition a patient from active UC to remission
      using oral and topical mesalazine compared with oral alone were L1812 and L2390,
      respectively. Improved remission rates attributed to oral and topical mesalazine
      resulted in moderate improvements in quality-adjusted life years (QALYs) compared
      to oral mesalazine alone. Disaggregation of medical costs indicated that medical
      consultations and diagnostic costs were similar for both treatment arms. An
      abbreviated analysis which considered costs up to steroid-refractory patients in
      subacute UC indicated that combination therapy offered a cost-savings of L285
      over 16 weeks of therapy compared with monotherapy. CONCLUSIONS: The results
      indicate that the addition of 1 g topical mesalazine results in significant cost
      savings and moderate quality of life improvements. We have also shown that
      irrespective of which treatment modality is used in steroid-refractory patients
      (eg, infliximab, azathioprine, ciclosporine) that topical mesalazine is cost
      saving.

PMID- 21172267
TI  - CC-10004 but not thalidomide or lenalidomide inhibits lamina propria mononuclear
      cell TNF-alpha and MMP-3 production in patients with inflammatory bowel disease.
AB  - BACKGROUND: Thalidomide, one of whose activities is to inhibit Tumour Necrosis
      Factor (TNF)-alpha production, has been reported to be an effective treatment for
      refractory inflammatory bowel disease (IBD). TNF-alpha driven production of
      matrix metalloproteinase (MMP)-3 by gut lamina propria mononuclear cells (LPMCs)
      is a major pathway of tissue injury in IBD; however the effect of thalidomide and
      newer more potent immunomodulatory derivatives on this pathway has not been
      studied. AIM: To investigate the effect of thalidomide, CC-4047 (pomalidomide),
      CC-5013 (lenalidomide), and CC-10004 (apremilast) on gut LPMC TNFalpha and MMP-3
      production in patients with IBD. METHODS: Gut LPMCs and myofibroblasts were
      isolated from patients with IBD, and cultured with thalidomide, CC-4047, CC-5013,
      and CC-10004. MMP-3 and TIMP-1 levels were determined by western blotting and
      real-time PCR, and TNF-alpha levels by ELISA. RESULTS: CC-10004 significantly
      reduced both TNF-alpha production and MMP-3 production by cultured LPMCs.
      Thalidomide and CC-4047 and CC-5013 had no significant effect on the production
      of TNF-alpha or MMP-3 by LPMCs. CONCLUSION: These results provides a mechanistic
      rationale for both the failure of lenalidomide (CC-5013) in a recent randomised
      controlled trial in Crohn's disease, and for the evaluation of CC-10004 as a
      novel oral therapy in the treatment of CD and UC.

PMID- 21172268
TI  - Construction of an ileocolic neosphincter - Nipple valve anastomosis for
      prevention of postoperative recurrence of Crohn's disease in the neoterminal
      ileum after ileocecal or ileocolic resection. A long-term follow-up study.
AB  - OBJECTIVE: To test the effect of an ileocolic neosphincter-nipple valve
      anastomosis after ileocolic resection for Crohn's disease, on the clinical and
      surgical recurrence-free survival, in a long-term follow-up pilot study.
      BACKGROUND AND AIMS: Fifty-nine patients, with Crohn's disease were operated on
      with an ileocecal or ileocolic resection and a nipple valve between 1993 and
      2007. METHODS: The nipple valve is constructed by everting the neoterminal ileum
      for a length of 4-5 cm and stabilized with 3 or 4 longitudinal stapler rows
      (N=36) or only in a basal zone (N=23). The nipple is telescoped with the tip
      pointed into the colon and the base of the nipple anastomosed to colon. Follow-up
      at regular intervals included clinical evaluation, Harvey-Bradshaw index,
      laboratory tests, colonoscopy and small bowel radiology when appropriate.
      RESULTS: The perioperative mortality was nil. Early postoperative complications
      were: wound infection (N=4), anastomotic leak (N=1), reoperated, nipple ischemia
      (N=1) reoperated, enterocutaneous fistula (N=1). Clinical recurrence in the
      neoterminal ileum was after 1, 3, 4 and 5 years: 11%, 20%, 23% and 24%. Eleven
      patients (19%) were reoperated for recurrence in the neoterminal ileum after
      median 96 months follow-up. The cumulative reoperation rate was after 1, 3, 4 and
      5 years: 4%, 13%, 13% and 16%, respectively. CONCLUSION: The low clinical and
      surgical recurrence rate in the neoterminal ileum may suggest a protective effect
      of the neosphincter on postoperative recurrence of Crohn's disease. This result
      should be tested in a randomized controlled trial.

PMID- 21172269
TI  - Association of a Nkx2-3 polymorphism with Crohn's disease and expression of Nkx2
      3 is up-regulated in B cell lines and intestinal tissues with Crohn's disease.
AB  - AIM: To replicate the association of Nkx2-3 rs10883365 SNP with Crohn's disease
      in patients from a familial IBD registry from the central Pennsylvania area and
      study mRNA and protein expression of Nkx2-3 in CD patients. MATERIALS AND
      METHODS: We genotyped the Nkx2-3 rs10883365 SNP in 75 CD patients,137 non-CD
      family members and 118 unrelated healthy controls from EBV-transformed B cell
      lines of a familial IBD registry in central Pennsylvania. mRNA and protein
      expression levels of Nkx2-3 were measured by RT-PCR and Western blot,
      respectively. RESULTS: rs10883365 was found to be associated with CD. A
      significant difference between the homozygous variant genotype (GG) compared to
      the wild type sequence (AA) was observed between CD and individuals without IBD,
      including both non-IBD family members from the familial IBD registry and
      unrelated healthy controls. However, there was not a significant difference
      between CD and non-IBD related family members. mRNA and protein expression levels
      of Nkx2-3 were increased in CD compared with non-CD sibling and healthy controls.
      A total of 16 sibling pairs were examined, and the mRNA and protein expression
      levels of Nkx2-3 from 12 of the sibling pairs (75%) were increased in the CD
      individual compared with the non-CD sibling. mRNA expression levels of Nkx2-3
      were increased in diseased tissues compared with adjacent normal tissues in 7 of
      9 patients (77.8%). CONCLUSIONS: Nkx2-3 is genetically associated with CD and is
      up-regulated in CD, suggesting that Nkx2-3 is involved in the pathogenesis of CD.

PMID- 21172270
TI  - Thiopurines, a previously unrecognised cause for fatigue in patients with
      inflammatory bowel disease.
AB  - BACKGROUND: Active inflammatory bowel disease, anaemia, iron deficiency and
      depression, alone or in combination, are known contributing factors of fatigue in
      inflammatory bowel disease. However, in some patients, fatigue cannot be
      attributed to known causes. Thiopurines are not a recognized cause. AIM: To
      describe the clinical scenario of a series of patients where thiopurines were the
      likely cause of fatigue. METHOD: The clinical scenario of 5 patients was examined
      with specific reference to the temporal association of thiopurine therapy with
      fatigue, the effect of its withdrawal and rechallenge, and drug specificity.
      RESULTS: The onset of severe fatigue was related to the introduction of
      azathioprine or 6-mercaptopurine, rapid relief was experienced on its withdrawal
      in all patients, and fatigue rapidly occurred on rechallenge. The speed of onset
      was rapid in two patients and in the context of gradual withdrawal of moderate
      steroid dose, but recurred rapidly on rechallenge when not on steroids.
      CONCLUSIONS: Marked fatigue is a previously unrecognized adverse effect of
      thiopurines. It does not appear to be drug-specific. Its onset might be masked by
      concurrent steroid therapy.

PMID- 21172271
TI  - Sjogren's syndrome in a patient with ulcerative colitis and primary sclerosing
      cholangitis: Case report and review of the literature.
AB  - Inflammatory bowel disease has been reported to co-exist with other autoimmune
      diseases. Sjogren's syndrome is an autoimmune disorder characterized by xerostomy
      and/or xerophthalmy. Sjogren's syndrome occurring in IBD has been very rarely
      reported. A 45-year old woman diagnosed ten years ago with ulcerative pancolitis
      and primary sclerosing cholangitis was referred to our outpatient IBD clinic
      because of xerostomy but not for xerophthalmy for the previous three months. The
      patient had been under azathioprine maintenance treatment (2 mg/kg) and achieved
      long-term disease remission for the past 4 years. Patient clinical examination
      and laboratory tests were unremarkable. Salivary gland biopsy and complete
      ophthalmologic investigation were performed and the patient was diagnosed with
      Sjogren's syndrome. Understanding sicca manifestations in IBD is difficult since
      the pathogenesis of this intestinal disorder is not yet clear. Of these complex
      autoimmune phenomena which occur along with IBD it is quite difficult to
      categorize concomitant Sjogren's syndrome as primary or secondary and literature
      is conflicting. The possibility of Sjogren's syndrome should always be considered
      and properly investigated in patients diagnosed with inflammatory bowel disease
      who develop a constellation of constitutional sicca symptoms.

PMID- 21172272
TI  - Use of Infliximab as rescue therapy in acute severe Ulcerative Colitis with
      recent norovirus infection.
AB  - BACKGROUND AND AIMS: Norovirus infection is a common cause of acute diarrhoeal
      illness and may occur in the setting of inflammatory bowel disease. METHODS: A
      patient with an acute severe first presentation of Ulcerative Colitis failed to
      settle with intravenous steroids and rescue therapy was considered. The isolation
      of norovirus in his stool caused concern about aggravating the infection if
      immunosuppression ensued. Following a brief period of watchful waiting and a full
      discussion between physician, surgeon and patient, Infliximab was administered (5
      mg/kg). RESULTS: The patient responded well both clinically and biochemically.
      CONCLUSIONS: In this case, Infliximab was a safe and efficacious intervention in
      a patient with acute Ulcerative Colitis and recent norovirus infection.

PMID- 21172273
TI  - Pulmonary Crohn's disease: A rare extra-intestinal manifestation treated with
      infliximab.
AB  - Crohn's disease is a chronic inflammatory bowel disease often presenting with
      extra-intestinal manifestations. However, pulmonary involvement is quite rare. We
      report a case of Crohn's disease with pulmonary extra-intestinal manifestation
      (bronchiolitis obliterans organizing pneumonia-like changes) treated with
      infliximab. Furthermore, we present an overview of cases of inflammatory bowel
      disease with lung involvement, treated with tumor necrosis factor-alpha
      antagonists. In this case, when infliximab was given, a significant resolution of
      the pulmonary changes was achieved.

PMID- 21172274
TI  - Reversible bilateral optic neuritis after Infliximab discontinuation in a patient
      with Crohn's disease.
AB  - A relationship between inflammatory bowel disease and multiple sclerosis is
      supported by a higher than expected coexistence of these diseases among families
      and individuals. A 32 year-old male with Crohn's disease of the terminal ileum
      diagnosed 4 years ago and HLA-B27 negative bilateral sacroiliitis diagnosed 2
      years ago, was admitted in our hospital because of an acute episode of blurred
      vision. In addition the patient complained for urine incontinence. Before this
      admission the patient was administered methylprednisolone and Infliximab
      induction treatment. During admission the diagnosis of multiple sclerosis
      associated bilateral optic neuritis was made and Infliximab was discontinued. The
      patient was started on therapy with interferon-beta for multiple sclerosis,
      prednizolone and azathioprine for Crohn's disease and oxybutynin hydrochloride
      for urine incontinence. After 8 weeks of Infliximab discontinuation patient
      recovered totally from optic neuritis. This is a rare case of totally reversible
      bilateral optic neuritis associated with multiple sclerosis in a patient with
      Crohn's disease and sacroiliitis receiving also Infliximab induction therapy.

PMID- 21172275
TI  - Suspension of smoking is a risk factor for Ulcerative Colitis (UC) diagnosed
      after an Acute Myocardial Infarction (AMI).

PMID- 21172276
TI  - Clinical, endoscopic and histological remission in paediatric chronically active
      ulcerative colitis after prolonged treatment with selective granulocyte-monocyte
      adsorptive apheresis.

PMID- 21172277
TI  - Monster parastomal pyoderma gangrenosum effectively treated by topical
      tacrolimus.

PMID- 21172278
TI  - Pulmonary and nodal tuberculosis in a patient with inflammatory bowel disease and
      HIV infection treated with infliximab.

PMID- 21172279
TI  - On the second European Panel on the Appropriateness of Crohn's disease Therapy
      (EPACT-II).

PMID- 21172280
TI  - Prescription of physical exercise in Crohn's disease.
AB  - BACKGROUND: Physical exercise may be potentially beneficial for recovering
      physical condition and improving quality of life in populations suffering from
      chronic conditions, but little is known about its effects on patients suffering
      from Crohn's disease. AIMS: To provide reasonable and conservative
      recommendations for exercise regimens that appear clinically safe and feasible in
      patients suffering from Crohn's disease. METHODS: Relevant clinical studies about
      the effects of physical exercise on Crohn's disease, written in English language
      and carried out with human subjects were reviewed. RESULTS: Few relevant clinical
      studies have evaluated the effects of an exercise intervention on patients
      experiencing Crohn's disease. There seem to be two main types of physical
      interventions that should be recommended: aerobic activity and muscular
      resistance training. CONCLUSIONS: Some basic guidelines about how to prescribe
      physical exercise in Crohn's disease can be provided. However, more research is
      needed as few studies have been carried out so far.

PMID- 21172281
TI  - Appropriateness of therapy for active Crohn's disease: Results of a
      multidisciplinary international expert panel-EPACT II.
AB  - The increasing number of trials testing management strategies for luminal Crohn's
      disease (CD) has not filled all the gaps in our knowledge and thus, in clinical
      practice, many decisions for CD patients have to be taken without the benefit of
      high-quality evidence. METHODS: A multidisciplinary European expert panel used
      the RAND Appropriateness Method to develop and rate explicit criteria for the
      management of individual patients with active, steroid-dependent (ST-D) and
      steroid-refractory (ST-R) CD. RESULTS: Overall, 296 indications pertaining to
      mild-to-moderate, severe, ST-D, and ST-R CD were rated. In anti-TNF naive
      patients, budesonide and prednisone were found to be appropriate for mild
      moderate CD, and infliximab (IFX) was appropriate when these had previously
      failed or had not been tolerated. In patients with a prior successful treatment
      by IFX, this drug, with or without co-administration of a thiopurine analog, was
      favoured. Other anti-TNFs were appropriate in the presence of intolerance or
      resistance to IFX. High-dose steroids, IFX or adalimumab were appropriate in
      severe active CD. For the 105 indications for ST-D or ST-R disease, the panel
      considered the thiopurine analogs, methotrexate, IFX, adalimumab, and surgery for
      limited resection, to be appropriate, depending on the outcome of prior
      therapies. Anti-TNFs were generally considered appropriate in ST-R. CONCLUSION:
      Steroids, including budesonide for mild-to-moderate CD, remain the first-line
      therapy for active luminal CD. Anti-TNFs, in particular IFX as shown by the
      amount of available evidence, remain the second-line therapy for most
      indications. Thiopurine analogs, methotrexate and anti-TNFs are favoured in ST-D
      patients and ST-R patients.

PMID- 21172282
TI  - Appropriate maintenance treatment for Crohn's disease: Results of a
      multidisciplinary international expert panel - EPACT II.
AB  - INTRODUCTION: Biological therapy has dramatically changed management of Crohn's
      disease (CD). New data have confirmed the benefit and relative long-term safety
      of anti-TNFalpha inhibition as part of a regular scheduled administration
      programme. The EPACT appropriateness criteria for maintenance treatment after
      medically-induced remission (MIR) or surgically-induced remission (SIR) of CD
      thus required updating. METHODS: A multidisciplinary international expert panel
      (EPACT II, Geneva, Switzerland) discussed and anonymously rated detailed,
      explicit clinical indications based on evidence in the literature and personal
      expertise. Median ratings (on a 9-point scale) were stratified into three
      assessment categories: appropriate (7-9), uncertain (4-6 and/or disagreement) and
      inappropriate (1-3). Experts ranked appropriate medication according to their own
      clinical practice, without any consideration of cost. RESULTS: Three hundred and
      ninety-two specific indications for maintenance treatment of CD were rated (200
      for MIR and 192 for SIR). Azathioprine, methotrexate and/or anti-TNFalpha
      antibodies were considered appropriate in 42 indications, corresponding to 68% of
      all appropriate interventions (97% of MIR and 39% of SIR). The remaining
      appropriate interventions consisted of mesalazine and a "wait-and-see" strategy.
      Factors that influenced the panel's voting were patient characteristics and
      outcome of previous treatment. Results favour use of anti-TNFalpha agents after
      failure of any immunosuppressive therapy, while earlier primary use remains
      controversial. CONCLUSION: Detailed explicit appropriateness criteria (EPACT)
      have been updated for maintenance treatment of CD. New expert recommendations for
      use of the classic immunosuppressors as well as anti-TNFalpha agents are now
      freely available online (www.epact.ch). The validity of these criteria should now
      be tested by prospective evaluation.

PMID- 21172283
TI  - Appropriate therapy for fistulizing and fibrostenotic Crohn's disease: Results of
      a multidisciplinary expert panel - EPACT II.
AB  - INTRODUCTION: Many therapeutic decisions in the management of fistulizing and
      fibrostenotic Crohn's disease (CD) have to be taken without the benefit of strong
      scientific evidence. For this reason, explicit appropriateness criteria for CD
      fistula and stenosis treatment were developed by a multidisciplinary European
      expert panel in 2004 with the aim of making them easily available on the Internet
      and thus allowing individual case scenario evaluation; these criteria were
      updated in 2007. METHODS: Twelve international experts convened in Geneva,
      Switzerland in December 2007. Explicit clinical scenarios, corresponding to real
      daily practice, were rated on a 9-point scale based on evidence from the
      published literature and panelists' own expertise. Median ratings were stratified
      into three categories: appropriate (7-9), uncertain (4-6) and inappropriate (1
      3). RESULTS: Overall, panelists rated 60 indications pertaining to fistulas.
      Antibiotics, azathioprine/6-mercaptopurine and conservative surgery are the
      mainstay of therapy for simple and complex fistulas. In the event of previous
      failure of azathioprine/6-mercaptopurine therapy, methotrexate and infliximab
      were considered appropriate for complex fistulas. The panel also rated 72
      indications related to the management of fibrostenotic CD. The experts considered
      balloon dilation, if the stricture was endoscopically accessible, stricturoplasty
      and bowel resection to be appropriate for small bowel fibrostenotic Crohn's
      disease, and balloon dilation and bowel resection appropriate for fibrostenotic
      colonic disease. In the presence of an ileocolonic or ileorectal anastomotic
      stricture of <7 cm, endoscopic balloon dilation, and bowel resection were
      considered appropriate. CONCLUSION: Antibiotics, azathioprine/6-mercaptopurine,
      and conservative surgery are the mainstay of therapy for fistulizing Crohn's
      disease. Infliximab is a therapeutic option in patients without prior response to
      immunosuppressant therapy. In fibrostenotic Crohn's disease, endoscopic balloon
      dilation, if feasible, or surgical therapy should be considered. These expert
      recommendations are available online (www.epact.ch). Prospective evaluation is
      now needed to test the validity of these appropriateness criteria in clinical
      practice.

PMID- 21172284
TI  - Appropriate management of special situations in Crohn's disease (upper gastro
      intestinal; extra-intestinal manifestations; drug safety during pregnancy and
      breastfeeding): Results of a multidisciplinary international expert panel-EPACT
      II.
AB  - INTRODUCTION: High-grade evidence is lacking for most therapeutic decisions in
      Crohn's disease. Appropriateness criteria were developed for upper gastro
      intestinal, extra-intestinal manifestations and drug safety during conception,
      pregnancy and breastfeeding in patients with Crohn's disease, to assist the
      physician in clinical decision making. METHODS: The European Panel on the
      Appropriateness of Crohn's Disease Therapy (EPACT II), a multidisciplinary
      international European expert panel, rated clinical scenarios based on evidence
      from the published literature and panelists' own clinical expertise. Median
      ratings (on a 9-point scale) were stratified into three categories: appropriate
      (7-9), uncertain (4-6 with or without disagreement) and inappropriate (1-3).
      Experts were also asked to rank appropriate medications by priority. RESULTS:
      Proton pump inhibitors, steroids, azathioprine/6-mercaptopurine and infliximab
      are appropriate for upper gastro-duodenal Crohn's disease; for stenosis,
      endoscopic balloon dilation is the first-line therapy, although surgery is also
      appropriate. Ursodeoxycholic acid is the only appropriate treatment for primary
      sclerosing cholangitis. Infliximab is appropriate for Pyoderma gangrenosum,
      ankylosing spondylitis and uveitis, steroids for Pyoderma gangrenosum and
      ankylosing spondylitis, adalimumab for Pyoderma gangrenosum and ankylosing
      spondylitis, cyclosporine-A/tacrolimus for Pyoderma gangrenosum. Mesalamine,
      sulfasalazine, prednisone, azathioprine/6-mercaptopurine, ciprofloxacin, and
      probiotics, may be administered safely during pregnancy or for patients wishing
      to conceive, with the exception that male patients considering conception should
      avoid sulfasalazine. Metronidazol is considered safe in the 2nd and 3rd
      trimesters whereas infliximab is rated safe in the 1st trimester but uncertain in
      the 2nd and 3rd trimesters. Methotrexate is always contraindicated at conception,
      during pregnancy or during breastfeeding, due to its known teratogenicity.
      Mesalamine, prednisone, probiotics and infliximab are considered safe during
      breastfeeding. CONCLUSION: EPACT II recommendations are freely available online
      (www.epact.ch). The validity of these criteria should now be tested by
      prospective evaluation.

PMID- 21172285
TI  - Enteric neuroglial apoptosis in inflammatory bowel diseases.
AB  - BACKGROUND: Enteric nervous system abnormalities have been described in patients
      with inflammatory bowel diseases. However, the mechanisms responsible for these
      abnormalities remain to date largely unknown. AIMS: We investigated the potential
      role of apoptotic phenomena in enteric neurons and enteroglial cells in patients
      with inflammatory bowel diseases. PATIENTS AND METHODS: Full-thickness surgical
      specimens of 19 patients undergoing surgery for medically refractory disease (9
      from the ileum of patients with Crohn's disease, 10 from the colon of patients
      with ulcerative colitis) were assessed for the presence of enteric neurons and
      enteroglial cells and for their apoptosis by two immunohistochemical methods, one
      also able to distinguish apoptosis from necrosis. The results were compared with
      those obtained in control specimens. RESULTS: Concerning Crohn's disease, the
      ileal segments displayed a significant increase of apoptotic enteric neurons and
      enteroglial cells in both the submucous and the myenteric plexus compared to
      controls. In patients with ulcerative colitis, compared to controls, apoptotic
      phenomena were significantly reduced in enteric neurons, whereas they were
      increased in the enteroglial cell population (submucous and myenteric plexus).
      CONCLUSIONS: In patients with inflammatory bowel disease apoptotic phenomena
      involve both enteric neurons and enteroglial cells, and may play a role in the
      abnormalities of the enteric nervous system. The importance of these findings in
      the pathophysiology of these conditions remains to be determined.

PMID- 21172286
TI  - Mucosal healing and steroid-sparing associated with infliximab for steroid
      dependent ulcerative colitis.
AB  - BACKGROUND: Corticosteroid therapy for ulcerative colitis (UC) frequently results
      in Steroid-dependency. The objective of this study was to evaluate the long term
      clinical and endoscopic efficacy of infliximab (IFX) in steroid-dependent UC.
      METHODS: An open-label, prospective, single center study was designed. Patients
      older than 18 years with steroid-dependent UC, either intolerant or did not
      respond to azathioprine, were consecutively enrolled. Steroid-dependency was
      defined as the ECCO criteria. Patients received IFX (5 mg/kg) at 0, 2 and 6 weeks
      and every 8 weeks thereafter for 2 years. All patients were clinically evaluated
      at weeks 8, 52 and 104 and a colonoscopy was performed at week 104. Response to
      IFX was defined as clinical remission without steroids together with mucosal
      healing (endoscopic Mayo score of 0 or 1). RESULTS: Seventeen consecutive
      patients were included (11 male, mean age 45, range 25-70). Thirteen (76%) had
      extensive colitis (E3). All patients completed IFX therapy. Clinical response was
      in 13/17 at weeks 8 and 52. Twelve out of seventeen patients maintained clinical
      remission without steroids and endoscopic response at week 104. Six out of
      seventeen patients needed dose intensification of IFX (every 6 weeks); 3/6
      patients did not reach remission despite dose intensification. Including those
      patients who needed dose intensification as non-responders, 9/17 patients were in
      clinical and endoscopic remission at week 104. A significant correlation was
      found between clinical and endoscopic findings (p<0.01). CONCLUSIONS: Infliximab
      therapy is effective for maintenance of clinical remission and mucosal healing in
      patients with steroid-dependent UC.

PMID- 21172287
TI  - Frequency of indeterminate colitis in children and adults with IBD - a
      metaanalysis.
AB  - BACKGROUND: Indeterminate colitis (IC) remains an enigmatic inflammatory bowel
      disease (IBD) phenotype. It is currently not clear whether it constitutes merely
      a problem of terminology, classification, or possibly an early stage of IBD
      distinct from Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We
      analysed epidemiological data of studies comparing IC, UC and CD. We selected 14
      studies investigating paediatric patients (10 prospective and 4 retrospective)
      and 18 studies investigating adult IBD patients (11 prospective and 7
      retrospective) for this analysis. RESULTS: Compared to adults (n=15,776) the
      frequency of IC is higher in children (n=6262) (children 12.7% versus adults
      6.0%, p<0.0001). This difference between children and adults has been detected
      irrespective whether prospective or retrospective studies were selected. In both,
      children and adults IC was more frequent in prospective studies compared to
      retrospective studies (children p=0.0004; adults p=0.0024). CONCLUSIONS: IC has
      been detected in a substantial proportion of paediatric patients with IBD. IC is
      more frequently found in children compared to adults. Further studies are
      required to clarify whether IC represents an IBD phenotype associated with
      childhood disease onset or whether the high IC frequency is due to difficulties
      in establishing a UC or CD diagnosis.

PMID- 21172288
TI  - The role of capsule endoscopy in small bowel Crohn's disease.
AB  - Video capsule endoscopy is an invaluable tool for examining the small bowel. It
      is non-invasive and generally well tolerated, however its role in the assessment
      of the severity and extent of small bowel Crohn's disease has not, to date, been
      adequately evaluated. METHODS: All capsule endoscopies performed over a two year
      period in a tertiary referral centre in subjects with known or suspected Crohn's
      disease were reviewed. RESULTS: Twenty-six capsule endoscopy studies in total
      were included. These were performed in 15 cases of known Crohn's disease, 5 cases
      of suspected Crohn's disease, 3 cases of endoscopically diagnosed non-specific
      terminal ileal inflammation and finally 3 post colectomy cases of indeterminant
      being considered for IPAA formation. Ten patients known to have small bowel
      Crohn's disease were prospectively recruited; of 3 with normal small bowel follow
      through or CT exams, one had an abnormal capsule endoscopy. The other 7 patients
      had small bowel follow through or abdominal CT scans consistent with small bowel
      Crohn's disease; additional mucosal abnormalities were detected by capsule
      endoscopy in 6 cases with capsule retention in the stomach in one. Of 5 with
      colonic Crohn's disease normal small bowel imaging corresponded with normal
      capsule endoscopy in all but one. A diagnosis of Crohn's disease was made in 2
      out of 5 cases of suspected Crohn's disease on the basis of the capsule endoscopy
      findings. Three patients with non-specific acute terminal ileal inflammation at
      ileocolonoscopy were confirmed to have ongoing inflammation. The capsule was
      retained in four subjects beyond 24 h. CONCLUSION: Capsule endoscopy more
      accurately determines the severity and extent of the Crohn's disease in the small
      bowel than traditional imaging modalities.

PMID- 21172289
TI  - Does the endoscopic appearance of the ileocecal valve suggest the severity of
      Crohn's disease in the terminal ileum?
AB  - Despite ileoscopy being the only procedure, which can accurately detect mucosal
      abnormalities in the ileum, it is performed only in 5-15% of the colonoscopies.
      AIM: The aim of this study was to retrospectively determine the predictive value
      of the endoscopic findings of the ileocecal valve (ICV) in patients with CD.
      METHODS: Data of 100 ileal or ileocolonic CD patients (45 females, 55 males, mean
      age 27.6 years, range 5-66), who underwent ileocolonoscopy between 2004 and 2008,
      were reviewed. Macroscopic appearance of the ICV and the endoscopic severity of
      the ileum evaluated by the Simple Endoscopic Score for Crohn's Disease were
      determined by re-evaluating the examinations recorded on DVDs in all cases.
      Histological scoring was performed in 56 cases. Statistical analyses were
      performed to assess relationships between the normal-looking ICV and the
      histological and endoscopic scores of the ileum and the correlation between the
      severity of the ileal inflammation and the macroscopic appearance of the ICV.
      RESULTS: A macroscopically normal appearance of the ICV was detected in 30
      patients. 60% of these patients were diagnosed with mild, 26.7% with moderate and
      13.3% with severe endoscopic ileal inflammation. ICV was affected by CD in 70
      patients, in whom significantly more severe ileal inflammation (p=0.005) was
      detected than in patients with normal-looking ICV. DISCUSSION: Our results
      suggest that ileal exploration should be attempted in every suspected CD
      patients, because, although the appearance of the ICV correlates with the
      severity of the ileal inflammation, a normal-looking ICV does not correspond to
      normal ileal mucosa in almost one third of the cases.

PMID- 21172290
TI  - IBD care in Europe: A comparative audit of the inpatient management of Crohn's
      disease and ulcerative colitis using the national UK IBD audit tool.
AB  - BACKGROUND AND AIMS: The National UK IBD audit tool is an electronic database
      created to improve the quality and safety of care for IBD patients by auditing
      individual patient care, service resources and organisation against national
      standards. We used the National UK IBD audit tool to compare the organisation and
      process of IBD care between services in Oxford (UK) and Milan (Italy), as a pilot
      study to evaluate its application outside national boundaries. METHODS: Clinical
      and demographic data of patients with CD and UC, consecutively admitted during a
      2month period, were collected and compared between the centres, to each other and
      to the UK IBD standards obtained by previous audit analyses performed in Oxford
      in 2006. RESULTS: 20 and 26 patients with UC were admitted in Oxford and Milan,
      as well as 21 and 20 patients with CD, respectively. Most admissions in Milan
      were planned admissions for moderately active treatment-refractory disease. No
      patient died. Oxford had a higher surgery rate. Endoscopy for UC consisted mainly
      of colonoscopy in Milan (92%) and flexible sigmoidoscopy in Oxford (64%). In CD,
      Oxford data revealed a higher use of immununomodulators and CT scan, compared
      with higher use of bowel ultrasound in Milan. CRP was the preferred biomarker of
      disease activity. The following areas did not reach the standards set for the
      2006 UK IBD Audit: the lack in Milan of IBD specialist nurses and few dietitian
      visits, as well as little attention to heparin prophylaxis and abdominal
      radiography in UC. Both sites paid little attention to stool cultures and
      revealed a high rate of active smokers in CD and little attention to bone
      protection in steroids users. Since the 2006 audit in Oxford, improvements
      include IBD specialist nurse visits, dietitian visits, number of active smokers,
      stool samples, prophylactic heparin, bone protection and nutritional assessment.
      CONCLUSIONS: Consistent procedural differences between Oxford and Milan
      identified by audits of both UC and CD could be resolved by organisational
      change, with an improvement in the service. The UK IBD audit tool is an easy
      instrument to assess the processes and outcomes of care delivery in IBD and can
      be applied also outside UK.

PMID- 21172291
TI  - Infliximab therapy for HIV positive Crohn's disease: A case report.
AB  - Anti-TNF-alpha is now established as a major player in the treatment of Crohn's
      disease, however the use of anti-TNF-alpha therapy in patients concomitantly
      having HIV infection and Crohn's disease is a relatively unexplored subject.
      There is generally some apprehension and anxiety to use infliximab in patients
      with HIV. One case has been reported in literature of usage of anti-TNF-alpha in
      HIV positive patient with Crohn's disease who was on anti-retroviral therapy. We
      report for the first time the successful usage of infliximab in treating Crohn's
      disease in an HIV positive patient who is not on any anti-retroviral treatment.

PMID- 21172292
TI  - Inflammatory pseudotumor of the liver associated with Crohn's disease.
AB  - Inflammatory liver pseudotumor is a rare entity. Associations with several
      inflammatory conditions were reported but association with inflammatory bowel
      disease is unusual. We report the case of liver inflammatory pseudotumor
      occurring in the course of Crohn's disease in a 23-year-old woman and treated
      conservatively.

PMID- 21172293
TI  - Azathioprine induced pneumonitis in a patient with ulcerative colitis.
AB  - Immunomodulator therapy with the thiopurine analogues azathioprine (AZA) or 6
      mercaptopurine (6-MP) is commonly prescribed for maintenance of remission in
      inflammatory bowel disease (IBD). Ten to twenty-five percent of patients have to
      withdraw from AZA or 6-MP due to adverse events that are partly explained by the
      relative activity of the drug metabolizing enzymes. Most of the potential major
      adverse events (myelosuppression, hepatotoxicity and pancreatitis) are well
      known. Pulmonary toxicity is rare but severe and may lead to respiratory
      insufficiency and even death. We describe a case of a young woman with ulcerative
      colitis (UC) who developed respiratory symptoms and fever combined with nodular
      densities and ground glass areas in both lungs on CT scan. An infection was ruled
      out and the diagnosis azathioprine induced pneumonitis was made. The drug was
      stopped and within one week her fever and respiratory symptoms resolved.
      Clinicians should be alert to this serious adverse event when treating patients
      with thiopurines.

PMID- 21172294
TI  - Pneumatosis intestinalis and hepatic portal venous gas in Crohn's disease.

PMID- 21172295
TI  - How can we really reduce the morbidity of inflammatory bowel disease - Research
      on genes and cytokines, or find out the causative factors in the environment?

PMID- 21172296
TI  - First evidence of spatial clustering of lymphatic filariasis in an Aedes
      polynesiensis endemic area.
AB  - Successful elimination of lymphatic filariasis (LF) requires accurate
      identification of residual foci of transmission and stringent surveillance
      strategies to combat potential resurgence. This is challenging in areas where the
      day-biting Aedes polynesiensis is endemic, such as Samoa, since in previous
      studies no geographical clustering of infection has been demonstrated. Another
      challenge for this low prevalence phase is the choice of diagnostic assay as
      testing for circulating filarial antigen (CFA) or microfilariae (Mf) alone may
      not have adequate sensitivity. This could be solved by using the commercially
      available filariasis Cellabs enzyme linked immunosorbent assay (CELISA) to
      measure antibody. In the current study five Samoan villages were chosen based on
      previous epidemiological assessments to represent a range of infection
      prevalences. CFA, Mf, and antibody levels in children <= 10 years had been
      recorded and results linked to household of residence and/or primary school of
      attendance. To ascertain the location of exposure, two scenarios based on
      potential foci of transmission around communities and schools were explored. Both
      scenarios revealed significant spatial clusters of households with infected
      individuals and a relationship to antibody positive children when they were
      included in the spatial analysis. Fasitoo-Tai had the highest LF prevalence and
      largest geographical spatial clusters for both scenarios. In Falefa, spatial
      clusters were detected only for the primary school scenario. In Tafua, which
      spanned an area of 19.5 km(2), no spatial clusters were detected. Lastly, in
      Siufaga, the village with the lowest LF prevalence, significant clustering of
      infected individuals was observed and, for the primary school scenario, this was
      geographically related to exposure. These promising findings are the first
      published evidence of spatial clustering of LF in a day-biting Ae. polynesiensis
      endemic area.

PMID- 21172297
TI  - Co-infection with Ascaris lumbricoides modulates protective immune responses
      against Giardia duodenalis in school Venezuelan rural children.
AB  - We evaluated the effect of Ascaris lumbricoides on Giardia duodenalis infection
      and TH1/TH2 type immune mechanisms toward this parasite in 251 rural parasitized
      and 70 urban non-parasitized school children. The children were classified
      according to light (0-5000 eggs/g faeces) or moderate (>5001-50,000 eggs/g
      faeces) A. lumbricoides infection. Anti G. duodenalis skin hyper-reactivity, IgE,
      IgG, IL-13, IFN gamma, IL6 and IL-10 levels were compared among G. duodenalis
      infected and non-infected children according to light or moderate A. lumbricoides
      infection. It was found that 62% of the A. lumbricoides moderately infected
      children were co-infected by G. duodenalis compared to 45% of the lightly
      infected group. After treatment, 42% of the A. lumbricoides moderately group were
      infected with G. duodenalis compared to 11% of their lightly counterparts, being
      A. lumbricoides IL-10 levels higher (p<0.0001) in the moderately infected group.
      In the A. lumbricoides lightly parasitized children, G. duodenalis infection was
      associated to a significant increase (p<0.005) of the levels of G. duodenalis IL
      13, IFN-gamma, IL-6, IgE, IgG and skin test hyper reactivity. In contrast, there
      was no effect of G. duodenalis infection in the elevation of these parameters
      among the A. lumbricoides moderately parasitized group, being those levels
      similarly lower as those observed in the control group. Inverse correlations were
      found between the levels of anti G duodenalis antibodies, skin test hyper
      reactivity and cytokines with the intensity of A. lumbricoides infection
      (p>0.0001) and A. lumbricoides IL-10 levels (p>0.0001), suggesting that co
      infection with A. lumbricoides may affect both TH1 and TH2 type immunity against
      G. duodenalis that may play an important role in the susceptibility to the
      infection after chemotherapy in children from endemic areas.

PMID- 21172298
TI  - DNA barcodes confirm the presence of a single member of the Anopheles
      maculipennis group in Morocco and Algeria: An. sicaulti is conspecific with An.
      labranchiae.
AB  - Anopheles labranchiae Falleroni is the only member of the Maculipennis Group
      known to occur in northern Africa; however, confusion exists as to the taxonomic
      status of its junior synonym, An. sicaulti Roubaud (type locality: near Rabat,
      Morocco). Based on morphological and behavioural distinctions, it has been
      suggested that Moroccan populations have been isolated from other North African
      populations by the Atlas Mountains, and that Moroccan populations may represent
      An. sicaulti, originally described as a variety of An. maculipennis Meigen. DNA
      barcodes (658bp of the mitochondrial COI gene) obtained from 89 An. maculipennis
      s.l. collected in Morocco (n=79) and Algeria (n=10) in 2007 and 2008 were used to
      determine if Moroccan populations are genetically isolated from those east of the
      Atlas Mountains (Algeria), and whether there is molecular evidence to support the
      presence of more than one member of the Maculipennis Group in the region. No
      evidence for speciation was found between Moroccan and Algerian populations, or
      within populations in northern Morocco. Moreover shared COI haplotypes between
      Algeria and Morocco indicate ongoing gene flow between populations in these
      countries, suggesting that the Atlas Mountains are not a boundary to gene flow in
      An. labranchiae. The synonymy of An. sicaulti with An. labranchiae is confirmed.
      That An. labranchiae comprises the same species in these North African countries
      is important for malaria control.

PMID- 21172299
TI  - In vivo biotinylated recombinant influenza A virus hemagglutinin for use in
      subtype-specific serodiagnostic assays.
AB  - There is an urgent need for robust subtype-specific serological tests to diagnose
      influenza A virus infections in poultry and mammals, including humans. Such
      assays require reliable subtype-specific sources of soluble and authentically
      folded seroreactive hemagglutinin (HA), one of the integral membrane proteins
      that determine the serological subtype of influenza viruses. To this purpose, a
      bigenic pFastBacDual baculovirus transfer vector allowing efficient invivo
      biotinylation of soluble HA homo-oligomers expressed via the secretory pathway
      was developed. An Avi-Tag allowed site-specific biotinylation by a coexpressed
      genetically modified BirA biotin ligase retained in the endoplasmic reticulum
      (ER). Highly seroreactive mono-biotinylated HA of recent H5 and H7 influenza A
      subtypes was secreted from recombinant baculovirus infected High-Five insect
      cells at levels sufficient to directly load streptavidin-coated enzyme-linked
      immunosorbent assay (ELISA) matrices, thereby avoiding any purification steps.
      The recombinant antigens retained authentic antigenicity, including conformation
      dependent epitopes involved in hemagglutination inhibition as detected by
      monoclonal antibodies. This is the first bigenic invivo biotinylation system
      established for use in insect cells with secretable recombinant membrane proteins
      biotinylated by an ER-retained variant of BirA biotin ligase. The proposed
      technique is expected to significantly increase flexibility in the design of
      subtype-specific assays, thereby expanding the power of influenzaA virus
      serodiagnosis.

PMID- 21172300
TI  - Novel antiangiogenic agents in dermatology.
AB  - Because angiogenesis underlies the pathogenesis of numerous conditions (cancer,
      psoriasis, macular degeneration), there is a pressing need for continued
      investigations into angiogenic signaling and potential drug targets.
      Antiangiogenic agents can be classified as either direct or indirect. Direct
      antiangiogenics act on untransformed endothelial cells to prevent differentiation
      and proliferation; indirect antiangiogenics act to inhibit factors involved in
      proangiogenic signaling. Agents currently available with dermatologic indications
      are few; while several established and novel biologics targeting various
      proangiogenic factors are currently being investigated for potential dermatologic
      uses, but the jury is still out on their efficacy and safety. In this review, we
      highlight our experience with a group of existing and novel, small molecules that
      combine several modes of action against angiogenesis in addition to other
      properties--triarylmethane dyes and fulvene derivatives.

PMID- 21172301
TI  - Characterization of porcine alpha-class glutathione transferase A1-1.
AB  - An alpha-class glutathione transferase (GST) has been cloned from pig gonads. In
      addition to two conservative point mutations our nucleotide sequence presents a
      frame shift resulting from a missing A as compared to a previously published
      porcine GST A1-1 sequence. The deduced C-terminal amino-acid segment of the
      protein differs between the two variants. Repeated sequencing of cDNA isolated
      from different tissues and animals ruled out the possibility of a cloning
      artifact, and the deduced amino acid sequence of our clone showed higher
      similarity to related mammalian GST sequences. Hereafter, we refer to our cloned
      enzyme as GST A1-1 and to the previously published enzyme as GST A1-1(*). The
      study of the tissue distribution of the GSTA1 mRNA revealed high expression
      levels in many organs, in particular adipose tissue, liver, and pituitary gland.
      Porcine GST A1-1 was expressed in Escherichia coli and its kinetic properties
      were determined using alternative substrates. The catalytic activity in steroid
      isomerization reactions was at least 10-fold lower than the corresponding values
      for porcine GST A2-2, whereas the activity with 1-chloro-2,4-dinitrobenzene was
      approximately 8-fold higher. Differences in the H-site residues of mammalian
      Alpha-class GSTs may explain the catalytic divergence.

PMID- 21172302
TI  - Essential role of two tyrosines and two tryptophans on the photoprotection
      activity of the Orange Carotenoid Protein.
AB  - Photosynthetic organisms have developed photoprotective mechanisms to protect
      themselves from lethal high light intensities. One of these mechanisms involves
      the dissipation of excess absorbed light energy into heat. In cyanobacteria,
      light activation of a soluble carotenoid protein, the Orange Carotenoid Protein
      (OCP), binding a keto carotenoid, is the key inducer of this mechanism. Blue
      green light absorption triggers structural changes within the carotenoid and the
      protein, leading to the conversion of a dark orange form into a red active form.
      Here we report the role in photoconversion and photoprotection of individual
      conserved tyrosines and tryptophans surrounding the rings of the carotenoid. Our
      results demonstrate that the interaction between the keto group of the carotenoid
      and Tyr201 and Trp288 is essential for OCP photoactivity. In addition, these
      amino acids are responsible for carotenoid affinity and specificity. We have
      already demonstrated that the aromatic character of Tyr44 and Trp110 interacting
      with the hydroxyl ring is critical. Here we show that the replacement of Tyr44 by
      Ser affects the stability of the red form avoiding its accumulation at any
      temperature, while Trp110Ser is affected in the energy necessary to the orange to
      red conversion and in the interaction with the antenna. Collectively our data
      support the idea that the red form is essential for photoprotection but not
      sufficient. Specific conformational changes occurring in the protein seem to be
      critical to the events leading to energy dissipation.

PMID- 21172303
TI  - Sodium influence on energy transduction by complexes I from Escherichia coli and
      Paracoccus denitrificans.
AB  - The nature of the ions that are translocated by Escherichia coli and Paracoccus
      denitrificans complexes I was investigated. We observed that E. coli complex I
      was capable of proton translocation in the same direction to the established
      deltapsi, showing that in the tested conditions, the coupling ion is the H(+).
      Furthermore, Na(+) transport to the opposite direction was also observed, and,
      although Na(+) was not necessary for the catalytic or proton transport
      activities, its presence increased the latter. We also observed H(+)
      translocation by P. denitrificans complex I, but in this case, H(+) transport was
      not influenced by Na(+) and also Na(+) transport was not observed. We concluded
      that E. coli complex I has two energy coupling sites (one Na(+) independent and
      the other Na(+) dependent), as previously observed for Rhodothermus marinus
      complex I, whereas the coupling mechanism of P. denitrificans enzyme is
      completely Na(+) independent. This work thus shows that complex I energy
      transduction by proton pumping and Na(+)/H(+) antiporting is not exclusive of the
      R. marinus enzyme. Nevertheless, the Na(+)/H(+) antiport activity seems not to be
      a general property of complex I, which may be correlated with the metabolic
      characteristics of the organisms.

PMID- 21172304
TI  - BTG2 is an LXXLL-dependent co-repressor for androgen receptor transcriptional
      activity.
AB  - The tumor suppressor gene, BTG2 has been down-regulated in prostate cancer and
      the ectopic expression of this gene has been shown to inhibit prostate cancer
      cell growth. Sequence analysis revealed that the BTG2 protein contains two
      leucine-rich motifs ((20)LxxLL(24) and (92)LxxLL(96)), which are usually found in
      nuclear receptor co-factors. Based on this, we postulated that there will be an
      association between BTG2 and AR. In this study, we discovered that BTG2 directly
      bound to the androgen receptor (AR) in the absence of 5alpha-dihydrotestosterone
      (DHT), and in the presence of the androgen, this interaction was increased. BTG2
      bearing the mutant (20)LxxLL(24) motif bound to AR equally efficient as the wild
      type BTG2, while BTG2 bearing the mutant (92)LxxLL(96) motif failed to interact
      with AR. Functional studies indicated that ectopic expression of BTG2 caused a
      significant inhibition of AR-mediated transcriptional activity and a decreased
      growth of prostate cancer cells. Androgen-induced promoter activation and
      expression of prostate-specific antigen (PSA) are significantly attenuated by
      BTG2. The intact (92)LxxLL(96) motif is required for these activities. These
      findings, for the first time, demonstrate that BTG2 complexes with AR via an
      LxxLL-dependent mechanism and may play a role in prostate cancer via modulating
      the AR signaling pathway.

PMID- 21172305
TI  - GLI1, a crucial mediator of sonic hedgehog signaling in prostate cancer,
      functions as a negative modulator for androgen receptor.
AB  - Sonic hedgehog (SHH) signaling, acting in a combinatorial manner with androgen
      signaling, is essential for prostate patterning and development. Recently,
      elevated activation of SHH signaling has been shown to play important roles in
      proliferation, progression and metastasis of prostate cancer. In this report, we
      demonstrate for the first time, that GLI1, which has been shown to play a central
      role in SHH signaling in prostate cancer, can act as a co-repressor to
      substantially block androgen receptor (AR)-mediated transactivation, at least in
      part, by directly interacting with AR. Our observations suggest that the SHH-GLI
      pathway might be one of determinants governing the transition of prostate cancer
      from anandrogen-dependent to an androgen-independent state by compensating, or
      even superseding androgen signaling.

PMID- 21172306
TI  - Testicular Sertoli cells influence the proliferation and immunogenicity of co
      cultured endothelial cells.
AB  - The major problem of the application of endothelial cells (ECs) in
      transplantation is the lack of proliferation and their immunogenicity. In this
      study, we co-cultured ECs with Sertoli cells to monitor whether Sertoli cells can
      influence the proliferation and immunogenicity of co-cultured ECs. Sertoli cells
      were isolated from adult testicular tissue. ECs were divided into the control
      group and the experimental group, which included three sub-groups co-cultured
      with 1 * 10(3), 1 * 10(4) or 1 * 10(5) cell/ml of Sertoli cells. The growth and
      proliferation of ECs were observed microscopically, and the expression of
      vascular endothelial growth factor (VEGF) receptor-2 (KDR) was examined by
      Western blotting. In another experiment, ECs were divided into the control group,
      the single culture group and the co-culture group with the optimal concentration
      of Sertoli cells. After INF-gamma and TNF-alpha were added to the culture medium,
      MHC II antigen expression was detected by immunofluorescence staining and western
      blotting; interleukin (IL)-6, IL-8 and soluble intercellular adhesion molecule
      (sICAM) were measured in the culture medium by ELISA. We demonstrated that 1 *
      10(4) cell/ml Sertoli cells promoted the proliferation of co-cultured ECs more
      dramatically than that in other groups (P<0.05). Western blotting showed that 1 *
      10(4) cell/ml of the Sertoli cells was most effective in the up-regulation of KDR
      expression in the co-cultured ECs (P<0.05). Sertoli cells can effectively
      suppress INF-gamma-induced MHC II antigen expression in co-cultured ECs compared
      with single culture group (P<0.05). TNF-alpha induced the expression of IL-6, IL
      8 and sICAM in ECs. When co-cultured with Sertoli cells, their expressions were
      significantly lower than in the EC single culture group (P<0.05). ECs co-cultured
      with Sertoli cells also did not significantly increase the stimulation index of
      spleen lymphocytes compared to the single culture group (P<0.05). Our results
      suggested that co-culturing with Sertoli cells can significantly promote the
      proliferation of ECs, accelerate post-transplant angiogenesis, while reduce EC
      immunogenicity and stimulus to lymphocytes.

PMID- 21172307
TI  - Translation of 5' terminal oligopyrimidine tract (5'TOP) mRNAs in Aplysia
      Californica is regulated by the target of rapamycin (TOR).
AB  - Aplysia californica is a model organism for determining the molecular basis of
      memory. In this system identified synaptic changes have been closely linked to
      behavioral memories. Long-term sensitization and long-term synaptic changes
      between sensory neurons and motor neurons require both gene expression followed
      by translational control of the newly expressed mRNAs. One important mechanism
      for translational control is mediated through the target of rapamycin (TOR) and
      one mechanism downstream of TOR is the translational control of mRNAs containing
      a 5' terminal oligopyrimidine tract (5'TOP) sequence in their mRNA transcript.
      These include all ribosomal proteins, elongation factors and a few other
      translational regulators. TOR regulation of 5'TOP mRNAs in vertebrates is thought
      to be due to TOR dependent removal of the translational repression mediated by
      the 5'TOP sequence. Here, we show that this mechanism is similar in Aplysia,
      whereby Aplysia 5'TOP mRNAs are repressed under basal conditions and this
      repression is removed by serotonin in a rapamycin-sensitive manner.

PMID- 21172308
TI  - Distinct fucosylation of M cells and epithelial cells by Fut1 and Fut2,
      respectively, in response to intestinal environmental stress.
AB  - The intestinal epithelium contains columnar epithelial cells (ECs) and M cells,
      and fucosylation of the apical surface of ECs and M cells is involved in
      distinguishing the two populations and in their response to commensal flora and
      environmental stress. Here, we show that fucosylated ECs (F-ECs) were induced in
      the mouse small intestine by the pro-inflammatory agents dextran sodium sulfate
      and indomethacin, in addition to an enteropathogen derived cholera toxin.
      Although F-ECs showed specificity for the M cell-markers, lectin Ulex europaeus
      agglutinin-1 and our monoclonal antibody NKM 16-2-4, these cells also retained EC
      phenotypes including an affinity for the EC-marker lectin wheat germ agglutinin.
      Interestingly, fucosylation of Peyer's patch M cells and F-ECs was distinctly
      regulated by alpha(1,2)fucosyltransferase Fut1 and Fut2, respectively. These
      results indicate that Fut2-mediated F-ECs share M cell-related fucosylated
      molecules but maintain distinctive EC characteristics, Fut1 is, therefore, a
      reliable marker for M cells.

PMID- 21172309
TI  - MicroRNA-101 downregulates Alzheimer's amyloid-beta precursor protein levels in
      human cell cultures and is differentially expressed.
AB  - The full repertoire of regulatory interactions utilized by human cells to control
      expression of amyloid-beta precursor protein (APP) is still undefined. We
      investigated here the contribution of microRNA (miRNA) to this regulatory
      network. Several bioinformatic algorithms predicted miR-101 target sites within
      the APP 3'-untranslated region (3'-UTR). Using reporter assays, we confirmed
      that, in human cell cultures, miR-101 significantly reduced the expression of a
      reporter under control of APP 3'-UTR. Mutation of predicted site 1, but not site
      2, eliminated this reporter response. Delivery of miR-101 directly to human HeLa
      cells significantly reduced APP levels and this effect was eliminated by co
      transfection with a miR-101 antisense inhibitor. Delivery of a specific target
      protector designed to blockade the interaction between miR-101 and its functional
      target site within APP 3'-UTR enhanced APP levels in HeLa. Therefore, endogenous
      miR-101 regulates expression of APP in human cells via a specific site located
      within its 3'-UTR. Finally, we demonstrate that, across a series of human cell
      lines, highest expression of miR-101 levels was observed in model NT2 neurons.

PMID- 21172310
TI  - Two successive neurocognitive processes captured by near-infrared spectroscopy:
      prefrontal activation during a computerized plus-shaped maze task.
AB  - The present study using near-infrared spectroscopy (NIRS) examined prefrontal
      activation associated with maze-solving performance in adult humans. The
      participants were required to solve a plus-shaped maze, comparable to the one
      used for pigeons and human children to behaviorally assess planning processes, by
      moving a target square to a goal square presented on a touch-sensitive screen.
      The participants made incorrect responses toward a previous goal immediately
      after the goal jumped to the end of another arm, in parallel with but less
      frequently than previous participants, with shorter reaction times than when they
      correctly adjusted their responses. In these incorrect trials, relatively larger
      hemodynamic changes having two peaks were observed, especially in channels near
      the right inferior frontal cortex (IFC), suggesting use of additional cognitive
      resources for adjustment of responses after making errors. In addition to showing
      human adults' better behavioral inhibition than previous participants, the
      present NIRS data suggest a difference in prefrontal activation patterns
      according to whether inhibition of the forward plan was working well or not. The
      results also testify to the effective NIRS recording, while the participants were
      moving a computer-generated stimulus by actually making finger touches to the
      monitor.

PMID- 21172311
TI  - Association between the 5-HTR1B gene polymorphisms and alcohol dependence in a
      Han Chinese population.
AB  - The human serotonin receptor 1B (HRT1B) plays an important role in regulating
      serotonin release. Previous research has suggested that the genetic variation of
      the HTR1B gene may confer susceptibility to alcoholism or some subtypes of
      alcohol dependence, but the evidence has been inconsistent. The aim of the
      present study is to examine whether polymorphic variants of the HTR1B gene are
      associated with alcohol dependence subtypes or drinking-related behaviors in
      Chinese Han population. Alcohol-dependent (AD) male patients (n=135) and controls
      (n=143) were genotyped for two polymorphisms: A161T in the promoter region and
      the synonymous variation G861C in the coding region of HTR1B. The results showed
      that the A161T polymorphism was associated with alcohol dependence (T vs. A
      allele: p=0.002; OR=2.18, 95% CI: 1.32-3.60). This association was strengthened
      in those with positive family history (OR=3.12, 95% CI: 1.71-5.70) and/or early
      onset (OR=4.53, 95% CI: 2.18-9.44) of alcohol dependence. The A161T variant was
      also significantly associated with age of onset of alcoholism (p=0.001).
      Furthermore, there was a significant difference of haplotypic frequencies between
      patients and controls (chi(2)=14.84, df=3, p=0.002), with one common haplotype AG
      of being significantly underrepresented among the patient group compared to the
      control group (34% vs. 47.7%, permutation p=0.0034; OR=0.56; 95% CI: 0.39-0.79).
      These findings confirm HTR1B as a susceptibility gene for alcohol dependence in
      the sample of Chinese Han population. The HTR1B A-161T polymorphism may be
      particularly valuable as a functional genetic marker for alcoholism and merits
      additional study.

PMID- 21172312
TI  - The N170 component and its links to configural face processing: a rapid neural
      adaptation study.
AB  - A neural adaptation paradigm where adaptor and test stimuli were presented in
      rapid succession was employed to investigate links between the face-sensitive
      N170 component and configural face processing. In Experiment 1, schematic adaptor
      stimuli preceded naturalistic images of upright faces, inverted faces, or
      isolated eyes. Relative to a baseline condition with schematic house adaptors,
      upright and inverted schematic faces adapted the N170 to subsequent naturalistic
      faces, demonstrating that this component is associated with neural processes
      involved in the analysis of first-order relational face configuration. In
      Experiment 2, two-tone Mooney faces adapted the N170 to naturalistic faces
      relative to a baseline condition with Mooney houses, suggesting links between the
      N170 and holistic face processing. Results demonstrate that the N170 component
      does not exclusively reflect the detection and analysis of individual face parts,
      but also the processing of first-order configural and global gestalt features of
      faces. They also show that neural adaptation procedures can be used to identify
      the neural mechanisms that are responsible for category-specific ERP components
      such as the N170.

PMID- 21172313
TI  - Lipoic acid protects against reperfusion injury in the early stages of cerebral
      ischemia.
AB  - Lipoic acid (LA) is a known antioxidant currently used as a therapy in patients
      with vascular and metabolic disorders. We tested the hypothesis that lipoic acid
      is protective against the cell death observed following stroke. Lipoic acid was
      administered 30minutes prior to, or immediately following removal of sutures used
      to occlude the middle cerebral artery (MCA) in male Sprague-Dawley rats.
      Following removal of the sutures, the MCA territory was allowed to undergo 5.5hrs
      of reperfusion. This ischemia/reperfusion (I/R) resulted in a focal infarct
      restricted to the prefrontal cortex (24+/-3mm(3)). Pretreatment with LA 30minutes
      prior to occlusion resulted in a dose-dependent reduction in infarct volume. This
      reduction in infarct volume was not observed when the LA was administered
      immediately prior to reperfusion (30minutes post-occlusion). To investigate a
      potential hemodynamic mechanism for this LA-induced neuroprotection, blood
      pressure, heart rate and baroreceptor reflex sensitivity (BRS) were measured.
      Intravenous administration of LA did not result in any significant changes in any
      of these parameters compared to saline-treated rats. Similarly, there was no
      significant contribution of systemic nitric oxide or alteration in cerebral
      perfusion measured following pretreatment with lipoic acid or during the course
      of occlusion and reperfusion compared with saline-treated rats. Western blot
      analysis of tissue from the ischemic cortex showed an increase in protein
      expression of superoxide dismutase (SOD2), but not SOD1, in LA pretreated rats.
      This suggests a potential mechanism of action contributing to the LA-induced
      neuroprotection observed. Furthermore, the data in the present investigation
      suggest the potential use of LA pretreatment as a neuroprotectant in stroke
      patients.

PMID- 21172314
TI  - Electrophysiological correlates of perceiving and evaluating static and dynamic
      facial emotional expressions.
AB  - Recent evidence suggests that dynamic facial expressions of emotion unfolding
      over time are better recognized than static images. However, the mechanisms
      underlying this facilitation are unclear. Here, participants performed expression
      categorizations for faces displaying happy, angry, or neutral emotions either in
      a static image or dynamically evolving within 150 ms. Performance replicated
      facilitation of emotion evaluation for happy expressions in dynamic over static
      displays. An initial emotion effect in event-related brain potentials evidenced
      in the early posterior negativity (EPN) was both enhanced and prolonged when
      participants evaluated dynamic in comparison to static facial expressions.
      Following the common interpretation of the EPN, this finding suggests that the
      facilitation for dynamic expressions is related to enhanced activation in visual
      areas starting as early as 200 ms after stimulus onset, presumably due to shifts
      of visual attention. Enhancement due to dynamic display was also found for the
      late positive complex (LPC), indicating a more elaborative processing of
      emotional expressions under this condition at subsequent stages.

PMID- 21172316
TI  - Brain oscillatory correlates of working memory constraints.
AB  - It has been claimed that the coordination of neuronal oscillations differing in
      frequency is relevant for cognition. However, the validity of this claim has
      scarcely been investigated. Recent studies revealed that cross-frequency phase
      coupling and modulations of alpha-power dissociate between retention of relevant
      and suppression of irrelevant information in visual working memory (WM). We
      summarize these important results, and discuss possible implications for
      understanding the neural mechanisms of WM constraints.

PMID- 21172315
TI  - Visual abnormalities associated with enhanced optic nerve myelination.
AB  - Expression of the constitutively active serine/threonine kinase Akt in
      oligodendrocytes results in enhanced myelination in the CNS. Here, we have
      examined the effects of this Akt overexpression on optic nerve structure and on
      optic nerve function, assessed using the visual evoked potential (VEP).
      Transgenic mice have been generated with the Plp promoter driving expression of a
      modified form of Akt, in which aspartic acids are substituted for Thr308 and
      Ser473. These Plp-Akt-DD (Akt-DD) mice, and littermate controls, were studied at
      different ages. Optic nerves were examined anatomically at 2 and 6 months of age.
      At 2 months of age, optic nerves were substantially thicker in Akt-DD mice,
      reflecting an increase in myelination of optic nerve axons. By electron
      microscopy, myelin thickness was increased in Akt-DD optic nerve, with extended
      paranodal domains having excess paranodal loops, and the density of nodes of
      Ranvier was reduced, relative to control mice. We recorded VEPs in response to
      strobe flash ganzfeld stimuli presented after overnight dark- and light-adapted
      conditions at ages ranging from 1 to 10 months. It was possible to record a clear
      VEP from Akt-DD mice at all ages examined. At 1 month of age, VEP implicit times
      were somewhat shorter in Akt-DD transgenic mice than in control animals. Beyond
      6months of age, VEP latencies were consistently delayed in Akt-DD transgenic
      mice. These abnormalities did not reflect an alteration in retinal function as
      there were no significant differences between ERGs obtained from control or Akt
      DD transgenic mice. In young mice, the somewhat faster responses may reflect
      improved transmission due to increased myelination of optic nerve axons. In older
      mice, where the Akt-DD optic nerve is markedly thicker than control, it is
      remarkable that optic nerves continue to function.

PMID- 21172317
TI  - Effects of short-term hormonal replacement on learning and on basal forebrain
      ChAT and TrkA content in ovariectomized rats.
AB  - It has been proposed that sex steroid hormones improve performance in some
      cognitive tasks by regulating the basal forebrain cholinergic function. However,
      the molecular basis of such influence still remains unknown. Current study
      analyzed the performance of ovariectomized rats in an autoshaping learning task
      after a short-term treatment with 17beta-estradiol (E2: 4 and 40MUg/kg) and/or
      progesterone (P4: 4mg/kg). These results were correlated with basal forebrain
      choline acetyltransferase (ChAT) and TrkA protein content. The high dose of E2
      enhanced both acquisition in the autoshaping task and the content of ChAT and
      TrkA. P4 treatment increased ChAT and TrkA content without affecting performance
      of rats in the autoshaping learning task. Interestingly, the continuous and
      simultaneous administration of E2 plus P4 did not significantly modify behavioral
      and biochemical evaluated parameters. These results address the influence of both
      E2 and P4 on cholinergic and TrkA activity and suggest that the effects of
      ovarian hormones on cognitive performance involve basal forebrain cholinergic
      neurons.

PMID- 21172318
TI  - Measuring Pavlovian fear with conditioned freezing and conditioned suppression
      reveals different roles for the basolateral amygdala.
AB  - In Pavlovian fear conditioning, pairing a neutral cue with aversive foot shock
      endows a cue with fear-eliciting properties. Studies of Pavlovian fear
      conditioning measuring freezing have demonstrated the basolateral amygdala (BLA)
      to be critical to both fear learning and memory. The nucleus accumbens core
      (NAc), while not important to freezing, is important to the enhancement of
      instrumental responding by cues paired with food reward. In the present study we
      investigated the role of the BLA and the NAc in another property of fear cues,
      the ability to suppress instrumental responding for food rewards (conditioned
      suppression). Sham, BLA and NAc-lesioned rats received a fear discrimination
      procedure in which one visual cue (CS+) predicted foot shock while a second cue
      (CS-) did not. Conditioning took place over a baseline of instrumental
      responding, allowing for concurrent measure of freezing and instrumental
      suppression. NAc lesions left fear conditioning fully intact. BLA lesions
      impaired acquisition and discrimination of fear when assessed with conditioned
      freezing. However, BLA lesions only altered fear acquisition and left
      discrimination completely intact when assessed with conditioned suppression.
      These findings suggest a critical role for the BLA in fear when assessed with
      conditioned freezing but a diminished role when assessed with conditioned
      suppression.

PMID- 21172319
TI  - The vesicular glutamate transporter-1 upstream promoter and first intron each
      support glutamatergic-specific expression in rat postrhinal cortex.
AB  - Multiple applications of direct gene transfer into neurons require restricting
      expression to glutamatergic neurons, or specific subclasses of glutamatergic
      neurons. Thus, it is desirable to develop and analyze promoters that support
      glutamatergic-specific expression. The three vesicular glutamate transporters
      (VGLUTs) are found in different populations of neurons, and VGLUT1 is the
      predominant VGLUT in the neocortex, hippocampus, and cerebellar cortex. We
      previously reported on a plasmid (amplicon) Herpes Simplex Virus vector that
      contains a VGLUT1 promoter. This vector supports long-term expression in VGLUT1
      containing glutamatergic neurons in rat postrhinal (POR) cortex, but does not
      support expression in VGLUT2-containing glutamatergic neurons in the ventral
      medial hypothalamus. This VGLUT1 promoter contains both the VGLUT1 upstream
      promoter and the VGLUT1 first intron. In this study, we begin to isolate and
      analyze the glutamatergic-specific regulatory elements in this VGLUT1 promoter.
      We show that the VGLUT1 upstream promoter and first intron each support
      glutamatergic-specific expression. We isolated a small, basal VGLUT1 promoter
      that does not support glutamatergic-specific expression. Next, we fused either
      the VGLUT1 upstream promoter or the first intron to this basal promoter. The
      VGLUT1 upstream promoter or the first intron, fused to the basal promoter, each
      supported glutamatergic-specific expression in POR cortex.

PMID- 21172320
TI  - Sex differences in adolescent white matter architecture.
AB  - BACKGROUND: Sex-specific trajectories in white matter development during
      adolescence may help explain cognitive and behavioral divergences between males
      and females. Knowledge of sex differences in typically developing adolescents can
      provide a basis for interpreting sexual dimorphisms in abilities and actions.
      METHOD: We examined 58 healthy adolescents (12-14years of age) with diffusion
      tensor imaging (DTI). Diffusion parameters fractional anisotropy (FA), and mean
      (MD), radial (RD), and axial diffusivities (AD) were subjected to whole-brain
      voxel-wise group comparisons using tract-based spatial statistics. Sex
      differences in white matter microstructure were examined in relation to pubertal
      development. RESULTS: Early adolescent females (n=29) evidenced higher FA in the
      right superior corona radiata, higher FA and AD in bilateral corticospinal tracts
      (>=164MUl, p<.01), and lower MD in the right inferior longitudinal fasciculus
      (ILF) and left forceps major (>=164MUl, p<.01) than age-matched males (n=29).
      Males did not show any areas of higher FA or lower MD than females, but had
      higher AD in the right superior longitudinal fasciculus, ILF, and forceps minor
      (>= 164MUl, p<.01). Pubertal stage did not account for sex disparities.
      CONCLUSION: In early adolescence, females' motor tracts may reflect widespread
      changes, while males may undergo relatively more microstructural change in
      projection and association fibers.

PMID- 21172321
TI  - Nitric oxide inhibition in paraventricular nucleus on cardiovascular and
      autonomic modulation after exercise training in unanesthetized rats.
AB  - It is well known that regular physical exercise alter cardiac function and
      autonomic modulation of heart rate variability (HRV). The paraventricular nucleus
      of hypothalamus (PVN) is an important site of integration for autonomic and
      cardiovascular responses, where nitric oxide (NO) plays an important role. The
      aim of our study was to evaluate the cardiovascular parameters and autonomic
      modulation by means of spectral analysis after nitric oxide synthase (NOS)
      inhibition in the PVN in conscious sedentary (S) or swimming trained (ST) rats.
      After swimming training protocol, adult male Wistar rats, instrumented with guide
      cannulas to PVN and femoral artery and vein catheters were submitted to mean
      arterial pressure (MAP) and heart rate (HR) recording. At baseline, the physical
      training induced a resting bradycardia (S: 374+/-5, ST: 346+/-1bpm) and promoted
      adaptations in HRV characterized by an increase in high-frequency oscillations
      (HF; 26.43+/-6.91 to 88.96+/-2.44) and a decrease in low-frequency oscillations
      (LF; 73.57+/-6.91 to 11.04+/-2.44) in normalized units. The microinjection of
      N(omega)-nitro-l-arginine methyl ester (l-NAME) in the PVN of sedentary and
      trained rats promoted increase in MAP and HR. l-NAME in the PVN did not
      significantly alter the spectral parameters of HRV of sedentary animals, however
      in the trained rats increased LF oscillations (11.04+/-2.44 to 27.62+/-6.97) and
      decreased HF oscillations (88.96+/-2.44 to 72.38+/-6.97) in normalized units
      compared with baseline. Our results suggest that NO in the PVN may collaborate to
      cardiac autonomic modulation after exercise training.

PMID- 21172322
TI  - Right parietal hypoactivation in a cocaine-dependent group during a verbal
      working memory task.
AB  - It has been suggested that cocaine addiction affects the engagement of the
      frontoparietal networks in executive functions, such as attention and working
      memory. Thus, our objective was to investigate brain differences between cocaine
      dependent subjects and healthy controls during the performance of a verbal
      working memory task. Nineteen comparison men and nineteen cocaine-dependent men
      performed a 2-back task. Data were acquired on a 1.5-T Siemens Avanto. Image
      processing and statistical analyses were carried out using SPM5; Biological
      Parametric Mapping (BPM) was used for further morphometric and correlation
      analyses. No performance differences were found between groups. However, the
      dorsal part of the right inferior parietal cortex (BA 40) was less activated in
      the cocaine-dependent group. Cocaine patients did not overactive any brain area
      when compared with controls. Our results show reduced activation in the brain
      areas related to the attention system in cocaine-dependent men while performing a
      verbal working memory task. Chronic cocaine use may affect the attentional system
      in the right parietal lobe, making patients more prone to attentional deficits.

PMID- 21172324
TI  - The action of thrombin in intracerebral hemorrhage induced brain damage is
      mediated via PKCalpha/PKCdelta signaling.
AB  - The present study investigates the role of protein kinase C alpha/delta
      (PKCalpha/PKCdelta) in brain injury induced by intracerebral hemorrhage (ICH) by
      utilizing a rat model that received intracerebral injections of autologous blood
      and thrombin (TM). The activation and expression of PKC and PKCdelta were
      analyzed by Western blot and immunohistochemistry. A PKC inhibitor,
      dihydrochloride (H7), was administrated intraperitoneally after injury to
      evaluate the effect of inhibition of PKC on ICH and TM induced brain damage. Our
      data indicate that both ICH and TM increased the expression of PKCalpha/PKCdelta
      in the brain tissue, and PKCalpha expression peaked at 6h, while PKCdelta
      expression reached its maximum value at 72h post-injury. Administration of H7
      significantly reduced the inflammatory cells infiltrate, permeability of brain
      blood barrier (BBB), brain edema, and neuronal death. We conclude that both
      PKCalpha and PKCdelta play important roles in ICH and TM-induced brain injury,
      and dihydrochloride (H7) can attenuate brain damage after ICH.

PMID- 21172323
TI  - Intracranial volume and dementia: some evidence in support of the cerebral
      reserve hypothesis.
AB  - The brain reserve hypothesis has been posited as being one important mediating
      factor for developing dementia, especially Alzheimer's disease (AD). Evidence for
      this hypothesis is mixed though different methodologies have made these findings
      difficult to interpret. We examined imaging data from a large cohort (N=194) of
      mixed dementia patients and controls, 65years old and older from the Cache
      County, Utah Study of Memory and Aging for evidence of the brain reserve
      hypothesis using total intracranial volume (TICV) as a quantitative measure of
      pre-morbid brain size and a vicarious indicator of reserve. A broader spectrum of
      non-demented elderly control subjects from previous studies was also included for
      comparison (N=423). In addition, non-parametric Classification and Regression
      Tree (CART) analyses were performed to model group heterogeneity and identify any
      subgroups of patients where TICV might be an important predictor of dementia.
      Parametrically, no main effect was found for TICV when predicting a dementia
      diagnosis; however, the CART analysis did reveal important TICV subgroups,
      including a sex differential wherein epsilon4 APOE allele presence in males and
      low TICV predicted AD classification. TICV, APOE, and other potential
      mediator/moderator variables are discussed in the context of the brain reserve
      hypothesis.

PMID- 21172326
TI  - An in vitro comparison of a new vinyl chalcogenide and sodium selenate on
      adenosine deaminase activity of human leukocytes.
AB  - Selenium (Se) is a dietary essential trace element with important biological
      roles. Sodium selenate (Na(2)SeO(4)) is an inorganic Se compound used in human
      and animal nutrition that acts as precursor for selenoprotein synthesis. The
      organoselenium 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one (C(21)H(2)HOSe)
      is an alpha,beta-unsaturated ketone functionalized vinyl chalcogenide that has
      been found as a potential tool in organic synthesis. Adenosine deaminase (ADA) is
      an important enzyme in the degradation of adenine nucleotides. In this study, we
      investigated the in vitro effects of both Se compounds on ADA activity and cell
      viability in leukocyte suspension (LS) of healthy donors (n=12). We first
      observed an inhibition of ADA activity using 0.1 MUM of 3-methyl-1-phenyl-2
      (phenylseleno)oct-2-en-1-one, and an increase in cellular viability when 30 MUM
      were used. However, we did not observe alterations in the presence of sodium
      selenate. Moreover, both Se compounds did not alter lactate dehydrogenase
      activity and thiobarbituric acid reactive substance levels. These results suggest
      that the inhibition of ADA activity caused by alpha,beta-unsaturated ketone may
      affect the adenosine levels in LS and modulate cell viability, attenuating
      conditions that involve the activation of the immune system.

PMID- 21172325
TI  - I remember you: a role for memory in social cognition and the functional
      neuroanatomy of their interaction.
AB  - Remembering events from the personal past (autobiographical memory) and inferring
      the thoughts and feelings of other people (mentalizing) share a neural substrate.
      The shared functional neuroanatomy of these processes has been demonstrated in a
      meta-analysis of independent task domains (Spreng, Mar & Kim, 2009) and within
      subjects performing both tasks (Rabin, Gilboa, Stuss, Mar, & Rosenbaum, 2010;
      Spreng & Grady, 2010). Here, we examine spontaneous low-frequency fluctuations in
      fMRI BOLD signal during rest from two separate regions key to memory and
      mentalizing, the left hippocampus and right temporal parietal junction,
      respectively. Activity in these two regions was then correlated with the entire
      brain in a resting-state functional connectivity analysis. Although the left
      hippocampus and right temporal parietal junction were not correlated with each
      other, both were correlated with a distributed network of brain regions. These
      regions were consistent with the previously observed overlap between
      autobiographical memory and mentalizing evoked brain activity found in past
      studies. Reliable patterns of overlap included the superior temporal sulcus,
      anterior temporal lobe, lateral inferior parietal cortex (angular gyrus),
      posterior cingulate cortex, dorsomedial and ventral prefrontal cortex, inferior
      frontal gyrus, and the amygdala. We propose that the functional overlap
      facilitates the integration of personal and interpersonal information and
      provides a means for personal experiences to become social conceptual knowledge.
      This knowledge, in turn, informs strategic social behavior in support of personal
      goals. In closing, we argue for a new perspective within social cognitive
      neuroscience, emphasizing the importance of memory in social cognition.

PMID- 21172327
TI  - Quantitative analysis of cholesterol nucleation with time in supersaturated model
      bile.
AB  - The amount of cholesterol (Ch) crystals formed in supersaturated
      taurochenodeoxycholate (TCDC) - lecithin (L) solutions of the same Ch saturation
      index (CSI) but at different Ch thermodynamic activities (Ch A(T)) was quantified
      at different time intervals. The initial Ch nucleation rate (i.e., amount of Ch
      crystals formed with respect to time) in a Ch A(T) = 1.73 and TCDC to L molar
      ratio (TCDC:L) = 5.1 system was faster than that in a Ch A(T) = 1.42 and TCDC:L =
      3.4 system. Shaking could enhance the early appearance of Ch crystals and cause
      the fast initial Ch nucleation rates for the TCDC:L = 5.1 and the TCDC:L = 3.4
      systems. The final Ch nucleation rates were faster than the initial Ch nucleation
      rates for the TCDC:L = 5.1 and the TCDC:L = 3.4 systems. According to a light
      scattering analysis of vesicle concentration in supersaturated TCDC-L solutions,
      vesicles provide nucleation sites only in the Ch nucleation process and the
      vesicle concentration may not be an important factor for the Ch nucleation rate.
      A model of a mixed TCDC-L micelle releasing Ch molecules together with the
      surface area of Ch crystals formed was used in the interpretation of the Ch
      nucleation.

PMID- 21172328
TI  - Pressure effects on lipid membrane structure and dynamics.
AB  - The effect of hydrostatic pressure on lipid structure and dynamics is highly
      important as a tool in biophysics and bio-technology, and in the biology of deep
      sea organisms. Despite its importance, high hydrostatic pressure remains
      significantly less utilised than other thermodynamic variables such as
      temperature and chemical composition. Here, we give an overview of some of the
      theoretical aspects which determine lipid behaviour under pressure and the
      techniques and technology available to study these effects. We also summarise
      several recent experiments which highlight the information available from these
      approaches.

PMID- 21172329
TI  - Routine polypectomy for colorectal polyps and ablation for Barrett's esophagus
      are intellectually the same.

PMID- 21172331
TI  - Treating hepatitis C: are children the same as adults?

PMID- 21172332
TI  - Yet another nucleoside analog for pancreatic cancer.

PMID- 21172334
TI  - A new player in neuromuscular transmission in the gastrointestinal tract.

PMID- 21172333
TI  - "ER stress(ed out)!": Paneth cells and ischemia-reperfusion injury of the small
      intestine.

PMID- 21172335
TI  - Glycated albumin is independently associated with estimated glomerular filtration
      rate in nondiabetic patients with chronic kidney disease.
AB  - BACKGROUND: Glycated albumin (GA) may contribute to diabetic nephropathy, but the
      clinical significance of GA in patients with chronic kidney disease (CKD) is
      unknown. METHODS: Patients were classified with the NKF/DOQI classification
      system as mild (stage I, II), moderate (stage III), or advanced CKD (stage IV).
      Those undergoing dialysis or with CKD stage V were excluded. GA was measured
      using the Lucica TM GA-L assay kit. The relationship between GA and renal
      dysfunction was analyzed in patients with or without diabetes. RESULTS: A total
      of 187 subjects were enrolled. GA values in those with normal, mild, moderate and
      advanced CKD were 18.4 +/- 1.4%, 18.4 +/- 3.1%, 19.0 +/- 3.8%, 20.4 +/- 6.4%,
      respectively, in diabetic patients (N=67, p=0.5), and were 14.1 +/- 1.9%, 14.2 +/
      2.2%, 15.9 +/- 1.9%, 15.0 +/- 1.7%, respectively, in nondiabetic patients
      (N=120, p=0.004). GA value was negatively correlated to eGFR in nondiabetic
      patients (r=-0.35, p<0.001) but not in diabetic patients (r=-0.11, p=0.39). In
      the adjusted model, GA is independently correlated to eGFR only in nondiabetic
      subjects. CONCLUSIONS: Increased GA concentrations are independently associated
      with renal dysfunction in nondiabetic patients with CKD.

PMID- 21172336
TI  - Fgf15-mediated control of neurogenic and proneural gene expression regulates
      dorsal midbrain neurogenesis.
AB  - The balanced proliferation and cell cycle exit of neural progenitors, by
      generating the appropriate amount of postmitotic progeny at the correct time and
      in the proper location, is required for the establishment of the highly ordered
      structure of the adult brain. Little is known about the extrinsic signals
      regulating these processes, particularly in the midbrain. Fibroblast growth
      factor (Fgf) 15, the mouse ortholog of FGF19 and member of an atypical Fgf
      subfamily, is prominently expressed in the dorsolateral midbrain of the
      midgestational mouse embryo. In the absence of Fgf15, dorsal midbrain neural
      progenitors fail to exit the cell cycle and to generate the proper amount of
      postmitotic neurons. We show here that this is due to the altered expression of
      inhibitory/neurogenic and proneural/neuronal differentiation helix-loop-helix
      transcription factor (TF) genes. The expression of Id1, Id3, and Hes5 was
      strongly increased and ectopically expanded, whereas the expression of Ascl1
      (Mash1), Neurog1 (Ngn1) and Neurog2 (Ngn2) was strongly decreased and
      transcription of Neurod1 (NeuroD) was completely abolished in the dorsolateral
      midbrain of Fgf15(-/-) mice. These abnormalities were not caused by the mis
      expression of cell cycle regulatory proteins such as cyclin-dependent kinase
      inhibitors or retinoblastoma proteins. Furthermore, human FGF19 promotes cell
      cycle exit of murine dorsal neural progenitors in vitro. Therefore, our data
      suggest that Fgf15 is a crucial signaling molecule regulating the postmitotic
      transition of dorsal neural progenitors and thus the initiation and proper
      progression of dorsal midbrain neurogenesis in the mouse, by controlling the
      expression of neurogenic and proneural TFs.

PMID- 21172337
TI  - FoxA transcription factors are essential for the development of dorsal axial
      structures.
AB  - In vertebrates, embryonic structures present at the dorsal midline, prechordal
      plate, notochord, hypochord and floor plate share a common embryonic origin. In
      zebrafish, they derive from a pool of progenitors located within the embryonic
      shield at the onset of gastrulation. The molecular mechanisms responsible for the
      common development of these structures remain unknown. Based on their spatial and
      temporal expression, transcription factors of the Forkhead box A (FoxA) family
      appeared to be good candidates to play such a role. In agreement with this
      hypothesis, we found that simultaneous knockdown of FoxA2 and FoxA3 abolish the
      formation of all axial derivatives, while overexpression of these transcription
      factors strongly enlarges dorsal mesodermal territories. We establish that, in
      FoxA2-FoxA3 double morphants, precursors of axial tissues are correctly induced
      at early gastrula stage, but their dorsal midline identity is not maintained
      during development and we found that progenitors of these tissues are cell
      autonomously re-specified to form muscle fibers as well as cells of the ventral
      neural tube. Our study provides the first example of a specific loss of all
      dorsal midline tissues and demonstrates that members of the FoxA family have
      redundant functions essential to maintain the axial identity of prechordal plate,
      notochord, floor plate and hypochord progenitors during gastrulation.

PMID- 21172338
TI  - Endosomal signalling of epidermal growth factor receptors contributes to EGF
      stimulated cell cycle progression in primary hepatocytes.
AB  - Agonist-induced internalisation of receptors may lead to the formation of
      signalling endosomes. There is little evidence relating to whether this occurs to
      native receptors in non-transformed cells, and no previous studies asking whether
      this endosomal signalling can promote cell cycle progression in non-transformed
      cells. We investigated the hypothesis that in primary hepatocytes clathrin
      dependent epidermal growth factor (EGF)-induced internalisation of the EGF
      receptor leads to signalling from endosomal EGF-EGF receptor complexes which may
      support EGF-stimulated cell cycle progression. We used EGF-stimulation of rat
      hepatocytes followed by confocal microscopy, and Western blots for
      phosphoproteins. [(3)H]thymidine incorporation into DNA was used as a indicator
      of progression to S-phase. Confocal microscopy demonstrated co-internalisation of
      EGF, EGF receptors and transferrin into endosomes. Internalisation of EGF/EGF
      receptor/transferrin was blocked by expression of dominant-negative dynamin, but
      not by the tyrosine kinase inhibitor AG 1478. Dominant-negative dynamin
      expression reduced EGF-stimulated extracellular signal-related kinase and Akt
      signalling, but increased tyrosine phosphorylated EGF receptor. EGF-stimulated
      cell cycle progression requires stimulation of EGF receptors during an initial
      period (e.g. 1h) and also later during a 24h incubation. EGF receptor
      internalisation in the presence of AG 1478 followed by removal of the inhibitor
      resulted in signalling from internalised EGF receptors that is sufficient for the
      initial stimulation to provide progression to S-phase of the cell cycle. These
      observations on hepatocytes characterise, for the first time in non-transformed
      cells, endosomal signalling from internalised EGF receptors, and provide evidence
      that this endosomal signalling may support the early phase of EGF-stimulated cell
      cycle progression.

PMID- 21172339
TI  - Effects of CNQX and MPEP on sensitization to the rewarding effects of morphine.
AB  - The present study was conducted to evaluate the influence of the glutamatergic
      receptors alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and
      metabotropic glutamate 5 (mGlu5) receptors on sensitization to the rewarding
      effects of morphine. The effects of pre-treatment with saline or 20mg/kg morphine
      plus the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (5
      or 10mg/kg) or the metabotropic Glu5 receptor antagonist 6-methyl-2
      (phenylethynyl)-pyridine (MPEP) (5 or 10mg/kg) on the place conditioning induced
      by a low dose of morphine (2mg/kg) were assessed. The 2mg/kg dose of morphine was
      ineffective in animals pre-treated with saline but induced a clear conditioned
      place preference (CPP) in mice pre-treated with morphine alone and morphine plus
      any of the MPEP doses or the lowest dose of CNQX. Conversely, animals pre-treated
      with morphine plus 10mg/kg of CNQX did not acquire CPP. Our results suggest that
      AMPA glutamate receptors are involved in the development of sensitization to the
      conditioned rewarding effects of morphine.

PMID- 21172340
TI  - The actions of benzophenanthridine alkaloids, piperonyl butoxide and (S)
      methoprene at the G-protein coupled cannabinoid CB1 receptor in vitro.
AB  - This investigation focused primarily on the interaction of two
      benzophenanthridine alkaloids (chelerythrine and sanguinarine), piperonyl
      butoxide and (S)-methoprene with G-protein-coupled cannabinoid CB(1) receptors of
      mouse brain in vitro. Chelerythrine and sanguinarine inhibited the binding of the
      CB(1) receptor agonist [(3)H]CP-55940 to mouse whole brain membranes at low
      micromolar concentrations (IC(50)s: chelerythrine 2.20 MUM; sanguinarine 1.10
      MUM). The structurally related isoquinoline alkaloids (berberine and papaverine)
      and the phthalide isoquinoline ((-)-beta-hydrastine) were either inactive or
      considerably below IC(50) at 30 MUM. Chelerythrine and sanguinarine antagonized
      CP-55940-stimulated binding of [(35)S] GTPgammaS to the G-protein (IC(50)s:
      chelerythrine 2.09 MUM; sanguinarine 1.22 MUM). In contrast to AM251, both
      compounds strongly inhibited basal binding of [(35)S]GTPgammaS (IC(50)s:
      chelerythrine 10.06 MUM; sanguinarine 5.19MUM). Piperonyl butoxide and S
      methoprene inhibited the binding of [(3)H]CP-55940 (IC(50)s: piperonyl butoxide
      8.2 MUM; methoprene 16.4 MUM), and also inhibited agonist-stimulated (but not
      basal) binding of [(35)S]GTPgammaS to brain membranes (IC(50)s: piperonyl
      butoxide 22.5 MUM; (S)-methoprene 19.31 MUM). PMSF did not modify the inhibitory
      effect of (S)-methoprene on [(3)H]CP-55940 binding. Our data suggest that
      chelerythrine and sanguinarine are efficacious antagonists of G-protein-coupled
      CB(1) receptors. They exhibit lower potencies compared to many conventional CB(1)
      receptor blockers but act differently to AM251. Reverse modulation of CB(1)
      receptor agonist binding resulting from benzophenanthridines engaging with the G
      protein component may explain this difference. Piperonyl butoxide and (S)
      methoprene are efficacious, low potency, neutral antagonists of CB(1) receptors.
      Certain of the study compounds may represent useful starting structures for
      development of novel/more potent G-protein-coupled CB(1) receptor blocking drugs.

PMID- 21172341
TI  - Contribution of the intracellular C terminal domain to regulation of human P2X1
      receptors for ATP by phorbol ester and Gq coupled mGlu(1alpha) receptors.
AB  - P2X1 receptors are expressed in arteries and blood platelets, play an important
      role in the cardiovascular system, and their activity can be potentiated
      following stimulation of Gq coupled receptors or phorbol ester treatment. The
      contribution of the intracellular carboxy terminus of the P2X1 receptor to this
      regulation was determined using over-expression of the C terminus and a
      mutagenesis based approach on recombinant receptors expressed in Xenopus oocytes.
      PMA induced potentiation of P2X1 receptor currents (~125% above control) was
      abolished following over-expression of the intracellular carboxy terminus of the
      P2X1 receptor. To determine the molecular basis of regulation by the carboxy
      terminus a series of individual cysteine point mutations between His(355) and
      Tyr(370) was characterized. PMA potentiation was abolished for the P2X1 receptor
      mutants H355C, P358C, Y363C, K367C, F368C, K369C and Y370C. When these mutations
      were introduced into the carboxy terminus fragment the inhibitory effect was
      absent only for P358C, K367C and Y370C mutants. These results suggest that
      residues Pro(358), Lys(367) and Tyr(370) are involved in the sequestering effect
      of the carboxy terminal fragment and indicate they are directly involved in
      modulation of the receptor by binding to a regulatory factor. The other mutants
      that abolished the PMA effect when introduced into the P2X1 receptor are likely
      to be involved in transduction of the regulatory event. These studies highlight
      the importance of the carboxy terminus in determining the properties and
      regulation of the P2X1 receptor and suggest that the intracellular terminal
      regions of the receptor close to the transmembrane segments interact.

PMID- 21172342
TI  - Lack of evidence that nebivolol is a beta3-adrenoceptor agonist.
AB  - Nebivolol is a selective beta1-adrenoceptor antagonist which, in addition,
      displays endothelium-dependent vasodilating properties in humans and other
      species. beta3-adrenoceptors have been proposed to be a molecular target of
      nebivolol-induced vasodilatation. Therefore, we have investigated possible beta3
      adrenoceptor agonism by nebivolol for relaxation of the human and rat urinary
      bladder (prototypical beta3-adrenoceptor-mediated responses) as well as for cAMP
      accumulation in Chinese hamster ovary cells stably transfected with the human
      beta-adrenoceptor subtypes. Nebivolol concentration-dependently relaxed both
      human and rat isolated urinary bladder strips but with low potency, similar to
      that reported for vasodilatation. However, nebivolol-induced bladder relaxation
      in either species was not inhibited by the beta3-adrenoceptor antagonist SR
      59,230A (10MUM), although this compound inhibited the isoprenaline-induced
      relaxation with the expected potency. In radioligand binding studies nebivolol
      had lower affinity for human beta3-adrenoceptors than the other two beta
      adrenoceptor subtypes, but this low affinity was in line with its potency to
      relax the bladder or isolated blood vessels. In functional studies nebivolol even
      in high concentrations did not stimulate cAMP formation via any of the three
      cloned human beta-adrenoceptors or in rat bladder smooth muscle cells. Taken
      together these data demonstrate that nebivolol can relax not only vascular but
      also urinary bladder smooth muscle. However, they do not support the hypothesis
      that nebivolol is an agonist at cloned human beta3-adrenoceptors or in rat or
      human urinary bladder.

PMID- 21172343
TI  - Janus activated kinase 2/signal transducer and activator of transcription 3
      pathway mediates icariside II-induced apoptosis in U266 multiple myeloma cells.
AB  - Although the flavonoid icariside II exhibits anti-inflammatory and anti-cancer
      activities, its molecular targets/pathways in human multiple myeloma cells are
      poorly understood. To analyze the effects on signal transducer and activator of
      transcription 3 (STAT3) signaling and apoptosis, U266 multiple myeloma cells were
      treated with icariside II and performed Western blotting, electrophoretic
      mobility gel shift assay (EMSA), RT-PCR, proliferation assay, cell cycle analysis
      and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.
      Icariside II inhibited STAT3 activation and enhanced the expression of SHP-1 and
      PTEN through inhibiting Janus activated kinase 2 (JAK2) and c-Src. Icariside II
      down-regulated the expression of STAT3 target genes Bcl-2, Bcl-x(L), survivin,
      cyclin D(1), COX-2 and vascular endothelial growth factor (VEGF). Also, icariside
      II enhanced poly (ADP-ribose) polymerase (PARP) cleavage and caspase-3
      activation. Pervanadate reversed the icariside II-mediated STAT3 inactivation and
      also blocked the cleavages of caspase-3 and PARP, suggesting involvement of STAT3
      pathway in icariside II-induced apoptosis. Furthermore, icariside II enhanced the
      apoptotic effects of clinically used drugs thalidomide and bortezomib in U266
      cells. Icariside II could be a potential therapeutic intervention agent alone or
      in combination with current drugs for multiple myeloma as a novel blocker of
      STAT3 signaling cascades at multiple levels, contributing to its anti
      proliferative and anti-apoptosis.

PMID- 21172345
TI  - Effect of long term, non cholesterol lowering dose of fluvastatin treatment on
      oxidative stress in brain and peripheral tissues of streptozotocin-diabetic rats.
AB  - One of the main goals of treatment of diabetes mellitus is to prevent its
      complications. Oxidative stress is universal in diabetes, being ultimately
      involved with the development complications. As a result of hyperglycemia,
      reactive oxygen/nitrogen species are produced in various tissues that leads to
      tissue damage with lipid peroxidation and protein oxidation, along with
      disruption in cellular homeostasis and accumulation of damaged molecules. Hence,
      supplementation with antioxidant compounds may offer some protection against
      diabetic complications. The pleiotropic effects of statins, including antioxidant
      and anti-inflammatory properties, represent an area of great interest in
      prevention and therapy of cardiovascular and neurological disorders. Using
      biomarkers of oxidative stress, in this study we examined the effect of non
      cholesterol lowering dose, long term fluvastatin treatment on oxidative stress in
      streptozotocin-diabetic rats. Experiments were conducted in 24 Wistar adult male
      rats. Diabetic and non-diabetic rats were treated orally for 6 months with
      fluvastatin (2mg/kg/day, p.o) starting one week after streptozotocin injection
      (55 mg/kg, i.p.), (preventive study). In brain, heart, liver, pancreas and kidney
      homogenates malondialdehyde, lipid hydroperoxide, protein carbonyl content,
      advanced oxidation protein products, 3-nitrotyrosine levels and superoxide
      dismutase, catalase activities were measured. Hyperglycemia and dyslipidemia in
      diabetic groups remained unchanged after fluvastatin treatment. The drug act as
      antioxidant in the tissues. Hence, antioxidant property of fluvastatin,
      independent of cholesterol lowering effect, may play a role in prevention of
      diabetic complications. Clinical relevance of this effect of fluvastatin seems
      worthy of further studies.

PMID- 21172344
TI  - The effects of nicotine, varenicline, and cytisine on schedule-controlled
      responding in mice: differences in alpha4beta2 nicotinic receptor activation.
AB  - Nicotine, varenicline, and cytisine are pharmacotherapies for tobacco dependence;
      the extent to which their in vivo effects vary as a function of differences in
      nicotinic acetylcholine receptor agonism is not clear. Male C57BL/6J mice
      responding under a fixed ratio 30 schedule of food delivery were used to
      establish the potency and time course of nicotine, varenicline, and cytisine;
      antagonism was examined with the non-competitive, non-selective antagonist
      mecamylamine and the competitive, alpha4beta2 nicotinic receptor antagonist
      dihydro-beta-erythroidine (DHbetaE). Intraperitoneal nicotine, varenicline, and
      cytisine dose-dependently decreased responding; nicotine was more potent (ED(50)
      value=0.83 mg/kg) than varenicline (ED(50) value=2.51 mg/kg) and cytisine (ED(50)
      value=2.97 mg/kg). The agonists had a similar time course including a rapid onset
      (5 min or less) and relatively short duration of action (30 min). Mecamylamine
      dose-dependently attenuated the rate-decreasing effects of a fixed dose of
      nicotine (1.78 mg/kg), varenicline (5.6 mg/kg), and cytisine (5.6 mg/kg).
      Mecamylamine (1mg/kg) produced parallel rightward shifts in the dose-response
      curves for nicotine (3.3-fold), varenicline (3.1-fold), and cytisine (2.3-fold).
      In contrast, DHbetaE (3.2mg/kg) produced 2-fold antagonism of nicotine and did
      not antagonize varenicline or cytisine. The data strongly suggest that nicotinic
      acetylcholine receptors mediate the effects of the agonists to decrease operant
      responding in mice. However, alpha4beta2 receptor agonism appears to contribute
      partially to the rate-decreasing effects of nicotine but not to the rate
      decreasing effects of varenicline and cytisine. Differential activation of
      alpha4beta2 receptors in vivo might contribute to differences in the
      effectiveness of these smoking cessation aids.

PMID- 21172346
TI  - Effect of kaempferol on lipid peroxidation and antioxidant status in 1,2-dimethyl
      hydrazine induced colorectal carcinoma in rats.
AB  - Colorectal cancer, a common cause of cancer related deaths in both sexes in
      western population is often due to persistent oxidative stress leading to DNA
      damage. Antioxidants scavenge free radicals and inhibit neoplastic process.
      Kaempferol, a flavonol widely distributed in tea, broccoli, grape fruit, brussels
      sprouts and apple, is claimed to have chemopreventive action in colon cancer. The
      aim of our study was to evaluate the effect of kaempferol on tissue lipid
      peroxidation and antioxidant status in 1,2-dimethyl hydrazine induced colorectal
      cancer in male Wistar rats and to compare its efficacy with irinotecan.
      Experimental colon cancer induced by 1,2-dimethyl hydrazine in rats mimic human
      colon cancer and therefore is an ideal model for chemoprevention studies. The
      rats were divided into six groups. Group 1 served as control. Group 2 received
      1,2-dimethyl hydrazine (20 mg/kg body weight) subcutaneously once a week for four
      weeks. Group 3 received irinotecan (100 mg/kg body weight) intravenously once a
      week for four weeks with 1,2-dimethyl hydrazine. Groups 4 to 6 were given a daily
      oral dose of 50, 100, 200 mg/kg body weight of kaempferol with 1,2-dimethyl
      hydrazine. The total study period was 16 weeks. Kaempferol supplementation
      lowered 1,2-dimethyl hydrazine induced erythrocyte lysate and liver
      thiobarbituric acid reactive substances level and rejuvenated anti oxidant
      enzymes catalase, super oxide dismutase and glutathione peroxidase. The recovery
      of enzyme status was maximum at the dose of 200 mg/kg body weight and was
      comparable to irinotecan. Our study reveals that kaempferol could be safely used
      as a chemopreventive agent in colorectal cancer.

PMID- 21172347
TI  - Modulation of Bax mitochondrial insertion and induced cell death in yeast by
      mammalian protein kinase Calpha.
AB  - Protein kinase Calpha (PKCalpha) is a classical PKC isoform whose involvement in
      cell death is not completely understood. Bax, a major member of the Bcl-2 family,
      is required for apoptotic cell death and regulation of Bax translocation and
      insertion into the outer mitochondrial membrane is crucial for regulation of the
      apoptotic process. Here we show that PKCalpha increases the translocation and
      insertion of Bax c-myc (an active form of Bax) into the outer membrane of yeast
      mitochondria. This is associated with an increase in cytochrome c (cyt c)
      release, reactive oxygen species production (ROS), mitochondrial network
      fragmentation and cell death. This cell death process is regulated, since it
      correlates with an increase in autophagy but not with plasma membrane
      permeabilization. The observed increase in Bax c-myc translocation and insertion
      by PKCalpha is not due to Bax c-myc phosphorylation, and the higher cell death
      observed is independent of the PKCalpha kinase activity. PKCalpha may therefore
      have functions other than its kinase activity that aid in Bax c-myc translocation
      and insertion into mitochondria. Together, these results give a mechanistic
      insight on apoptosis regulation by PKCalpha through regulation of Bax insertion
      into mitochondria.

PMID- 21172348
TI  - Environmental enrichment alters gene expression of steroidogenic enzymes in the
      rat hippocampus.
AB  - Neuroactive steroids are synthesized in the central and peripheral nervous
      systems. The purpose of this study was to analyze the effects of environmental
      enrichment on neuroactive steroidogenesis in the rat hippocampus. Environmental
      enrichment rats were housed in a group of nine in a large cage and three groups
      of pair-housed rats were housed in a standard cage for 8 weeks. The levels of
      mRNAs for steroidogenic enzymes and proteins in hippocampus were quantified by
      real-time RT-PCR. Environmental enrichment increased the mRNA expression levels
      of 5alpha-reductase-1 and 3alpha-hydroxysteroid dehydrogenase, which catalyze
      synthesis of allopregnanolone from progesterone. Hence, environmental enrichment
      appears to affect allopregnanolone synthesis.

PMID- 21172349
TI  - Activity and turnover of eosinophil and neutrophil granulocytes are altered in
      visceral leishmaniasis.
AB  - Visceral leishmaniasis (VL) is a health issue in Sudan. Our aim was to
      investigate the involvement of eosinophils and neutrophils in VL by serum and
      plasma measurements of eosinophil cationic protein (ECP) and myeloperoxidase
      (MPO) and some key cytokines and chemokines. Blood was collected from 125 VL
      patients and 181 healthy Sudanese controls from the same rural area. Results
      showed reduced eosinophil and neutrophil counts in the VL group (P=0.0001 and
      P=0.002, respectively). Serum-ECP levels were higher in the controls (P<0.0001),
      while plasma MPO levels were higher in the VL group (P<0.0001). Levels of IL-5,
      granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-17 were
      increased among the VL group (P<0.0001, P=0.017 and P=0.03, respectively),
      whereas eotaxin and IL-8 levels were reduced (P<0.0001 and P=0.002,
      respectively). Positive correlations were found between IL-8 and ECP/MPO
      (P<0.0001). We conclude that eosinophil and neutrophil turnover and activity are
      increased in subjects in rural areas of Sudan. In VL the turnover was further
      increased, but the relatively low secretory activity of eosinophils and
      neutrophils in VL may relate to the reduced production and availability of the
      chemokines eotaxin and IL-8. The combined assay of ECP and MPO in serum and
      plasma provides further insight into the mechanisms of eosinophil and neutrophil
      involvement in disease and constitutes a novel approach to the study of disease
      processes.

PMID- 21172350
TI  - Multiple origins of European populations of the giant liver fluke Fascioloides
      magna (Trematoda: Fasciolidae), a liver parasite of ruminants.
AB  - The giant liver fluke, Fascioloides magna, a liver parasite of free-living and
      domestic ruminants of Europe and North America, was analysed in order to
      determine the origin of European populations and to reveal the biogeography of
      this originally North American parasite on the European continent. The variable
      fragments of the mitochondrial cytochrome c oxidase subunit I (cox1; 384bp) and
      nicotinamide dehydrogenase subunit I (nad1; 405bp) were used. Phylogenetic trees
      and haplotype networks were constructed and the level of genetic structuring was
      evaluated using population genetic tools. In F. magna individuals originating
      from all European foci of infection (Italy, Czech Republic and Danube floodplain
      forests involving the territories of Slovakia, Hungary and Croatia) and from four
      of five major North American enzootic areas, 16 cox1 and 18 nad1 haplotypes were
      determined. The concatenated sequence set produced 22 distinct haplotypes. The
      European fluke populations were less diverse than those from North America in
      that they contained proportionately fewer haplotypes (eight), while a more
      substantial level of genetic diversity and a greater number of haplotypes (15)
      were recorded in North America. Only one haplotype was shared between the
      European (Italy) and North American (USA/Oregon and Canada/Alberta) flukes,
      supporting a western North American origin of the Italian F. magna population.
      Haplotypes found in Italy were distinct from those determined in the remaining
      European localities which indicates that introduction of F. magna to the European
      continent occurred more than once. In the Czech focus of infection, a south
      eastern USA origin was revealed. Identical haplotypes, common to parasites from
      the Czech Republic and from an expanding focus in Danube floodplain forests,
      implies that the introduction of F. magna to the Danube region came from an
      already established Czech focus of infection.

PMID- 21172352
TI  - The kinetics of local cytokine and galectin expression after challenge infection
      with the gastrointestinal nematode, Haemonchus contortus.
AB  - Gastrointestinal nematode parasites undergo several developmental stages within
      their mammalian host, each presenting different antigenic challenges to the
      immune system. To examine the expression of different immune mediators over time,
      biopsy samples were collected from the cannulated abomasum (true stomach) of
      immune sheep at several times after a challenge infection with Haemonchus
      contortus L3s. IL-5 and IL-13 mRNA expression levels were significantly increased
      above saline-challenged control levels at 5 and 7 days post challenge, while IL-4
      showed an earlier peak at day 2 post challenge. IL-5, IL-13 and IL-4, as well as
      IFN-gamma mRNA levels, peaked at 7 days before decreasing to non-significant
      levels at 28 days post challenge. TNF-alpha followed a similar profile while
      there was a slight increase in TGF-beta in both control and challenged sheep.
      There was a significant increase in galectin-14 mRNA in the L3 challenged
      compared with the saline challenged group at 7 days while both galectin-11
      protein and mRNA levels increased significantly by day 3 post challenge, peaking
      at 5-7 days post challenge. Distinct correlations were observed between these
      immune parameters at different times after L3 challenge. The galectin-14 protein
      level at day 2 post challenge was the only measured mediator significantly
      negatively correlated with worm burden. These studies highlight the dynamic
      nature of the immune response during parasite infection and the need to consider
      the different life cycle stages involved.

PMID- 21172351
TI  - Characterisation of hookworm heat shock factor binding protein (HSB-1) during
      heat shock and larval activation.
AB  - When hookworm infective L3s infect their mammalian host, they undergo a
      temperature shift from that of the ambient environment to that of their
      endothermic host. Additionally, L3s living in the environment can be exposed to
      temperature extremes associated with weather fluctuations. The heat shock
      response (HSR) is a conserved response to heat shock and other stress that
      involves the expression of protective heat shock proteins (HSPs). The HSR is
      controlled by heat shock factor-1 (HSF-1), a conserved transcription factor that
      binds to a heat shock element in the promoter of HSPs, causing their expression.
      HSF-1 is negatively regulated in part by a HSF binding protein (HSB-1) that binds
      to and removes HSF-1 trimers bound to HSP gene promoters, resulting in
      attenuation of the HSR. Herein we describe an HSB-1 orthologue, Ac-HSB-1, from
      the hookworm Ancylostoma caninum. The Ac-hsb-1 cDNA encodes a 79 amino acid
      protein that is 71% identical to the Caenorhabditis elegans HSB-1, and is
      predicted to share the characteristic coiled-coil structural motif comprised of
      two interacting alpha helices. Recombinant Ac-HSB-1 immunoprecipitated Ce-HSF-1
      expressed in mammalian cells that had been heat shocked for 1h at 42 degrees C,
      but not from cells incubated at 37 degrees C, indicating that HSB-1 only bound to
      the active DNA binding form of HSF-1. Expression of Ac-hsb-1 transcripts
      decreased following 1h of heat shock, but increased when L3s were incubated at 37
      degrees C for 1h. Activation of hookworm L3s induces a five-sixfold increase in
      Ac-hsb-1 expression that peaks at 12h, coincident with L3 feeding, but that
      subsequently decreases to two-threefold above control at 24h. Recombinant Ac-HSB
      1 immunoprecipitates greater amounts of 70 and 40kDa proteins from extracts of
      activated L3s than from non-activated L3s. We propose that an increase in Ac-hsb
      1 levels early in activation allows feeding to resume, but that a subsequent
      decrease in expression permits a HSR that protects non-developing L3s at host
      like temperatures. Further investigations of the HSR will clarify the role of HSB
      1 and HSF-1 in hookworm infection.

PMID- 21172353
TI  - Construction and molecular characterization of mouse single-chain variable
      fragment antibodies against Burkholderia mallei and Burkholderia pseudomallei.
AB  - We have selected two lipopolysaccharide (LPS) specific Burkholderia mallei mouse
      monoclonal antibodies (mAbs) and four anti-capsular B. pseudomallei-specific mAbs
      to generate mouse single-chain variable fragment (scFv) antibodies. This
      selection was made through extensive in vitro and in vivo assay from our library
      of mAbs against B. mallei and B. pseudomallei. We initially generated the mouse
      immunoglobulin variable heavy chain (VH) and light chain (VL) regions from each
      of these six selected mAbs using a phage display scFv technology. We determined
      the coding sequences of the VH and VL regions and successfully constructed two B.
      mallei-specific scFv phage antibodies consisting of two different VH (VH1 and
      VH2) and one Vlambda1 families. Four scFvs constructed against B. pseudomallei
      had two VH (VH1 and VH6) and two VL (Vkappa4/5 and Vkappa21) families. All of six
      scFv antibodies constructed demonstrated good binding activity without any rounds
      of biopanning against B. mallei (M5D and M18F were 0.425 and 0.480 at OD405nm)
      and B. pseudomallei (P1E7, P2I67, P7C6, and P7F4 were 0.523, 0.859, 0.775, and
      0.449 at OD405nm) by ELISA, respectively. A comparison of the immunoglobulin gene
      segments revealed that the gene sequences in complementarity-determining regions
      (CDRs) of three out of four B. pseudomallei-specific scFvs are highly conserved.
      We determined that the two B. mallei-specific scFvs have different CDRs in the
      VH, but the amino acid sequences of CDRs in the VL are conserved. This high
      sequence homology found in CDRs of VH or VL of these mAbs contributes to our
      better understanding and determination of binding to the specific antigenic
      epitope(s). The scFv phage display technology may be a valuable tool to develop
      and engineer mAbs with improved antigen-binding affinity.

PMID- 21172354
TI  - Absence of amplification role of the protein KLH on antibody response generated
      by a MAP Staphyloccocus aureus enterotoxin A (SEA) peptide comparing with the
      corresponding monomeric peptide.
AB  - Staphuloccocus aureus enterotoxin A (SEA) is a toxin involved in numerous food
      poisoning cases. To develop a detection test specific for this toxin, different
      approaches have been envisaged to obtain the highest antibody titer sera against
      a peptide sequence from this protein. The present work compares the properties of
      antibodies raised against the peptide epitope by classical and multiple antigen
      peptide (MAP) system approaches. Different immunization protocols were used:
      BALB/c mice were immunized either with the peptide or the MAP alone in Freund's
      adjuvant, co-immunized with the keyhole limpet hemocyanin (KLH) protein or, with
      the peptide, conjugated to this carrier KLH protein. The extent of reaction of
      the antibodies to the MAP construct with the parent protein was found to be
      significantly less than the antibodies raised against the monomeric peptide co
      immunized with or conjugated to a carrier protein but more that the antibodies
      raised against the peptide alone. Inversely, co-immunization of the MAP with the
      KLH was not able to raise the immune response as it was observed with the
      monomeric peptide. The results suggest that, for the epitope chosen here, MAP
      constructs were not the most effective option to induce sera with high levels of
      antibodies that react with the native protein.

PMID- 21172355
TI  - Honeybee (Apis mellifera ligustica) drone embryo proteomes.
AB  - Little attention has been paid to the drone honeybee (Apis mellifera ligustica)
      which is a haploid individual carrying only the set of alleles that it inherits
      from its mother. Molecular mechanisms underlying drone embryogenesis are poorly
      understood. This study evaluated protein expression profiles of drone
      embryogenesis at embryonic ages of 24, 48 and 72h. More than 100 reproducible
      proteins were analyzed by mass spectrometry on 2D electrophoresis gels. Sixty-two
      proteins were significantly changed at the selected three experimental age
      points. Expression of the metabolic energy requirement-related protein peaked at
      the embryonic age of 48h, whereas development and metabolizing amino acid-related
      proteins expressed optimally at 72h. Cytoskeleton, protein folding and
      antioxidant-related proteins were highly expressed at 48 and 72h. Protein
      networks of the identified proteins were constructed and protein expressions were
      validated at the transcription level. This first proteomic study of drone
      embryogenesis in the honeybee may provide geneticists an exact timetable and
      candidate protein outline for further manipulations of drone stem cells.

PMID- 21172356
TI  - Seminal fluid reduces female longevity and stimulates egg production and sperm
      trigger oviposition in a moth.
AB  - Previous studies suggest that a number of factors in relation to mating may
      reduce female longevity and stimulate egg production and oviposition. However, it
      is still not clear whether these factors act on these parameters independently or
      in a collective way. Here we carried out a series of experiments including mating
      trials and seminal fluid injection to determine the factors responsible for
      reducing female longevity and stimulating egg production and oviposition in
      relation to mating in the moth Ephestia kuehniella Zeller (Lepidoptera:
      Pyralidae). Results show that seminal fluid and sperm work collectively to allow
      females to achieve maximum realized fecundity (number of eggs laid) in E.
      kuehniella but these factors play different roles in the process and their
      actions are independent. Seminal fluid signals females to allocate resources to
      ova, resulting in shorter longevity and greater egg production while eupyrene
      (not apyrene) sperm in the spermatheca trigger females to lay maximum number of
      eggs. We suggest that the receptors for seminal fluid signal may be located in
      the female reproductive tract and haemolymph, and those for sperm signal may be
      in the spermatheca. Hypotheses that females prolong their longevity by
      oosorption, physical injuries by males reduce female longevity, and mechanical
      stimulation by males triggers oviposition, are not substantiated in the present
      study.

PMID- 21172358
TI  - Involvement of CD36 and intestinal alkaline phosphatases in fatty acid transport
      in enterocytes, and the response to a high-fat diet.
AB  - The vertebrate intestine is notable for its plasticity in response to
      environmental, pathologic, reproductive, and dietary challenges. The molecular
      mechanisms of intestinal adaptations typically involve both morphologic and
      functional changes. In response to chronic ingestion of a high-fat diet, for
      example, the mammalian small intestine quickly adapts to efficiently accommodate
      increased transport of long-chain fatty acids across the mucosa. Whereas this may
      be adaptive in the short term, in the long term it may contribute to the
      pathologies associated with chronic high-fat diets in humans and other mammals.
      This review focuses on some of the known and putative mechanisms by which fatty
      acids are transported across the intestinal epithelium in addition to simple
      diffusion, and how these mechanisms may be regulated in part by a high-fat diet.
      A model is proposed in which two key proteins, CD36 and the enzyme intestinal
      alkaline phosphatase, work in a coordinated manner to optimize fatty acid
      transport across enterocytes in mice.

PMID- 21172357
TI  - Caveolin-1 negatively regulates a metalloprotease-dependent epidermal growth
      factor receptor transactivation by angiotensin II.
AB  - A metalloprotease, ADAM17, mediates the generation of mature ligands for the
      epidermal growth factor receptor (EGFR). This is the key signaling step by which
      angiotensin II (AngII) induces EGFR transactivation leading to hypertrophy and
      migration of vascular smooth muscle cells (VSMCs). However, the regulatory
      mechanism of ADAM17 activity remains largely unclear. Here we hypothesized that
      caveolin-1 (Cav1), the major structural protein of a caveolae, a membrane
      microdomain, is involved in the regulation of ADAM17. In cultured VSMCs,
      infection of adenovirus encoding Cav1 markedly inhibited AngII-induced EGFR
      ligand shedding, EGFR transactivation, ERK activation, hypertrophy and migration,
      but not intracellular Ca(2+) elevation. Methyl-beta-cyclodextrin and filipin,
      reagents that disrupt raft structure, both stimulated an EGFR ligand shedding and
      EGFR transactivation in VSMCs. In addition, non-detergent sucrose gradient
      membrane fractionations revealed that ADAM17 cofractionated with Cav1 in lipid
      rafts. These results suggest that lipid rafts and perhaps caveolae provide a
      negative regulatory environment for EGFR transactivation linked to vascular
      remodeling induced by AngII. These novel findings may provide important
      information to target cardiovascular diseases under the enhanced renin
      angiotensin system.

PMID- 21172359
TI  - Automated experimental system capturing three behavioral components during murine
      forced swim test.
AB  - AIMS: An automated experimental system applying a commercially available video
      image analyzer was developed for the simultaneous detection and measurement of
      three behavioral components; immobility, swimming (horizontal movements) and
      climbing (vertical movements) that occur in the murine forced swim test (FST).
      The system was validated using four typical antidepressants. MAIN METHODS: System
      validity was confirmed by demonstrating no significant difference in 6 min time
      course of control group and imipramine-dosed group (30 mg/kg) between manual
      examinations and automated digital analysis for all the three behaviors (i.e.,
      correlation coefficients were 0.96, 0.83 and 0.94 for immobility, swimming and
      climbing, respectively). The effects of acute single treatment with four
      antidepressants in clinical use, i.e., imipramine, desipramine, bupropion and
      fluvoxamine were evaluated at doses of 15, 30 and 60 mg/kg using the system. KEY
      FINDINGS: In 2-4 min time span analysis, all four antidepressants reduced
      immobility and increased climbing significantly, desipramine and bupropion
      increased swimming significantly, while imipramine and fluvoxamine did not.
      SIGNIFICANCE: The automated experimental system enabled efficient and accurate
      analysis of the three murine behaviors during FST at once. Climbing could be more
      sensitive parameter to detect anti-depressant-like effect than immobility in this
      system.

PMID- 21172360
TI  - Thiamethoxam, a poor agonist of nicotinic acetylcholine receptors expressed on
      isolated cell bodies, acts as a full agonist at cockroach cercal afferent/giant
      interneuron synapses.
AB  - Thiamethoxam (TMX) is a second-generation neonicotinoid which is known to induce
      toxic effects on insects and mammalians. Recently, it has been proposed that TMX
      is a poor agonist of insect nicotinic acetylcholine receptors (nAChRs) on
      isolated cell bodies. Here, we have studied its effect on synaptic transmission.
      Our results demonstrate that TMX acts as an agonist of nAChRs expressed on
      cockroach cercal afferent giant/interneuron synapses as bath applications of TMX
      induce a strong reversible depolarization of the sixth abdominal ganglion. This
      response was reduced by the nicotinic antagonists mecamylamine and
      methyllicaconitine, but was insensitive to d-tubocurarine. Interestingly, TMX
      induced depolarization was partially reduced by the muscarinic antagonist
      atropine, suggesting that TMX could bind to a 'mixed nicotinic/muscarinic'
      receptor. Compared to previous studies, we proposed that TMX is able to act as
      agonist of insect nAChRs expressed at cercal afferent/giant interneuron synapses.
      Moreover, our results suggest that nAChRs expressed on synaptic ganglion are
      distinct to nAChRs expressed on isolated cell bodies and that synaptic receptors
      have higher affinity to TMX resulting to a depolarization of postsynaptic
      nicotinic receptors.

PMID- 21172361
TI  - Acidic pH facilitates peripheral alphabetameATP-mediated nociception in rats:
      differential roles of P2X, P2Y, ASIC and TRPV1 receptors in ATP-induced
      mechanical allodynia and thermal hyperalgesia.
AB  - Peripheral ischemia is commonly associated with an increase in tissue ATP
      concentration and a decrease in tissue pH. Although in vitro data suggest that
      low tissue pH can affect ATP-binding affinities to P2 receptors, the mechanistic
      relationship between ATP and low pH on peripheral nociception has not been fully
      examined. This study was designed to investigate the potential role of an
      acidified environment on intraplantar alphabetameATP-induced peripheral pain
      responses in rats. The mechanical allodynia (MA) produced by injection of
      alphabetameATP was significantly increased in animals that received the drug
      diluted in pH 4.0 saline compared to those that received the drug diluted in pH
      7.0 saline. Moreover, animals injected with alphabetameATP (100 nmol) in pH 4.0
      saline developed thermal hyperalgesia (TH), which did not occur in animals
      treated with alphabetameATP diluted in pH 7.0 saline. To elucidate which
      receptors were involved in this pH-related facilitation of alphabetameATP-induced
      MA and TH, rats were pretreated with PPADS (P2 antagonist), TNP-ATP (P2X
      antagonist), MRS2179 (P2Y1 antagonist), AMG9810 (TRPV1 antagonist) or amiloride
      (ASIC blocker). Both PPADS and TNP-ATP dose-dependently blocked pH-facilitated
      MA, while TH was significantly reduced by pre-treatment with MRS2179 or AMG9810.
      Moreover, amiloride injection significantly reduced low pH-induced facilitation
      of alphabetameATP-mediated MA, but not TH. These results demonstrate that low
      tissue pH facilitates ATP-mediated MA via the activation of P2X receptors and
      ASICs, whereas TH induced by ATP under low pH conditions is mediated by the P2Y1
      receptor and TRPV1, but not ASIC. Thus distinct mechanisms are responsible for
      the development of MA and TH under conditions of tissue acidosis and increased
      ATP.

PMID- 21172362
TI  - Oleoylethanolamide: effects on hypothalamic transmitters and gut peptides
      regulating food intake.
AB  - Recently, it has been described the role of fatty acid ethanolamides in the
      control of feeding behavior. Oleoylethanolamide (OEA) is a member of this family
      of lipid mediators regulating feeding. OEA acts suppressing feeding behavior
      through, at least partially, a peripheral mechanism. However, the interaction
      between this acylethanolamide and other orexigenic or anorexigenic mediators is
      mostly not well characterized. The aim of this study was to evaluate whether
      anorectic actions of OEA were mediated through the modulation of central and
      peripheral signals involved in the regulation of feeding. Experiments were
      performed in male Wistar rats under free-feeding and fasting conditions. We
      measured hypothalamic neuropeptides and monoamines by in situ hybridization and
      HPLC respectively as well as plasmatic levels of relevant endocrine signals. OEA
      administration induced changes in hypothalamic monoaminergic activity and in the
      anorexigenic neuropeptide CART expressed in the paraventricular nucleus (PVN) but
      lacked effect on neuropeptides expression in nucleus arcuatus. In addition, OEA
      induced peripheral changes in gut peptides, with marked effects on PYY and
      Ghrelin. These results further suggest that anorexigenic properties of OEA are
      mediated by peripheral signals and by central alterations in neuropeptides
      expressed by feeding-involved hypothalamic structures receiving input from
      peripheral sensory systems, such as the PVN.

PMID- 21172363
TI  - The role of the pulvinar in resolving competition between memory and visual
      selection: a functional connectivity study.
AB  - Memory and attention interact. Information held in working memory (WM) can bias
      visual selection toward matching stimuli in a subsequent search display, while a
      search target that is different from the memory stimulus can interfere with its
      subsequent recognition. In recent fMRI studies, the pulvinar has been
      consistently shown to have an enhanced response when an item in WM matches a
      search target and a reduced response when the WM item matches a distracter in
      search. Here we used Granger causality analysis to help understand the role of
      the pulvinar in resolving competition between memory and selection processes.
      Across three experiments the results showed increased coupling between the
      pulvinar and the ipsilateral superior frontal gyrus, contralateral temporal
      parietal junction (TPJ) and calcarine sulcus when a visual search distracter
      matched the item held in memory. This connection pattern suggests that the
      pulvinar suppresses visual responses to the target when a contralateral
      distracter contains information held in working memory. We propose that this
      suppression acts to protect the memory item from interference arising from
      information associated with the search target. Consistent with this proposal we
      showed that the strength of the thalamus-to-visual connection predicted
      performance on a subsequent memory test. The data therefore suggest that the
      thalamus modulates bottom up processing in sensory cortex to minimize
      interference to WM content.

PMID- 21172364
TI  - Storage and binding of object features in visual working memory.
AB  - An influential conception of visual working memory is of a small number of
      discrete memory "slots", each storing an integrated representation of a single
      visual object, including all its component features. When a scene contains more
      objects than there are slots, visual attention controls which objects gain access
      to memory. A key prediction of such a model is that the absolute error in
      recalling multiple features of the same object will be correlated, because
      features belonging to an attended object are all stored, bound together. Here, we
      tested participants' ability to reproduce from memory both the color and
      orientation of an object indicated by a location cue. We observed strong
      independence of errors between feature dimensions even for large memory arrays (6
      items), inconsistent with an upper limit on the number of objects held in memory.
      Examining the pattern of responses in each dimension revealed a gaussian
      distribution of error centered on the target value that increased in width under
      higher memory loads. For large arrays, a subset of responses were not centered on
      the target but instead predominantly corresponded to mistakenly reproducing one
      of the other features held in memory. These misreporting responses again occurred
      independently in each feature dimension, consistent with 'misbinding' due to
      errors in maintaining the binding information that assigns features to objects.
      The results support a shared-resource model of working memory, in which
      increasing memory load incrementally degrades storage of visual information,
      reducing the fidelity with which both object features and feature bindings are
      maintained.

PMID- 21172366
TI  - Influence of diurnal phase on startle response in adult rats exposed to
      dexamethasone in utero.
AB  - Depression and pathological anxiety disorders are among the most prevalent
      neurological diseases in the world and can be precipitated and exacerbated by
      stress. Prenatal stress alters both behavioral and endocrine responses to
      stressful stimuli in later life. We have previously observed increased basal
      acoustic startle response (ASR) in Wistar rats exposed to stress or dexamethasone
      (DEX) in utero when tested during the light phase of the circadian rhythm, and
      decreased prepulse inhibition (PPI) in similar animals tested during the dark
      phase of the cycle. We speculated that this observation of increased basal
      startle might be influenced by diurnal phase. In the present study, adult female
      Sprague Dawley rats, stressed prenatally with DEX (200 MUg/kg, gestational days
      14-21) and postnatally by blood sampling under restraint, were tested for the ASR
      during both circadian phases (light and dark). Basal startle was increased in
      animals tested both during the light and the dark phases of the cycle. We hereby
      replicated our earlier findings in a new strain and laboratory, thus
      strengthening the validity of our model regarding prenatal stress effects on ASR
      in female offspring. Our results indicate that observation of increased basal ASR
      is not solely dependent on diurnal phase. We found no difference in hippocampal
      glucocorticoid and mineral corticoid receptor expression between groups.

PMID- 21172365
TI  - Individual differences in novelty-seeking behavior in rats as a model for
      psychosocial stress-related mood disorders.
AB  - Most neuropsychiatric disorders, including stress-related mood disorders, are
      complex multi-parametric syndromes. Diagnoses are therefore hard to establish and
      current therapeutic strategies suffer from significant variability in
      effectiveness, making the understanding of inter-individual variations crucial to
      unveiling effective new treatments. In rats, such individual differences are
      observed during exposure to a novel environment, where individuals will exhibit
      either high or low locomotor activity and can thus be separated into high (HR)
      and low (LR) responders, respectively. In rodents, a long-lasting, psychosocial,
      stress-induced depressive state can be triggered by exposure to a social defeat
      procedure. We therefore analyzed the respective vulnerabilities of HR and LR
      animals to long-lasting, social defeat-induced behavioral alterations relevant to
      mood disorders. Two weeks after four daily consecutive social defeat exposures,
      HR animals exhibit higher anxiety levels, reduced body weight gain, sucrose
      preference, and a marked social avoidance. LR animals, however, remain
      unaffected. Moreover, while repeated social defeat exposure induces long-lasting
      contextual fear memory in both HR and LR animals, only HR individuals exhibit
      marked freezing behavior four weeks after a single social defeat. Combined, these
      findings highlight the critical involvement of inter-individual variations in
      novelty-seeking behavior in the vulnerability to stress-related mood disorders,
      and uncover a promising model for posttraumatic stress disorder.

PMID- 21172367
TI  - Central melanocortins modulate mesocorticolimbic activity and food seeking
      behavior in the rat.
AB  - The hypothalamic melanocortin system is known for its role in regulating energy
      homeostasis through it actions within hypothalamic brain centers. However,
      emerging evidence suggests that this system regulates addictive behaviors through
      signaling within mesolimbic neurons. Here, we hypothesized the melanocortin
      system modulates feeding behavior through its actions on mesolimbic neurons. In
      particular, we predicted that central administration of the melanocortin
      antagonist agouti-related peptide (AgRP) would activate midbrain dopamine
      neurons, increase mesolimbic dopamine turnover, and alter food seeking behaviors.
      We found that intraventricular administration of agouti-related peptide increased
      neuronal activation within midbrain dopamine neurons in addition to increasing
      dopamine turnover in the medial prefrontal cortex. Additionally, using the
      conditioned place preference paradigm to assay food seeking behavior, we report
      that central injection of agouti-related peptide attenuates the acquisition of a
      conditioned place preference for sucrose, but not high fat diet. These results
      suggest that the melanocortin system is capable of regulating mesocorticolimbic
      activity and food seeking behavior.

PMID- 21172368
TI  - Changes in sensory perception of sports drinks when consumed pre, during and post
      exercise.
AB  - The aim of this study was to examine sensory perceptions towards different
      formulations of sports drinks when consumed before, at various points during, and
      following exercise. Following familiarization 14 recreational runners underwent
      four trials in a single blind counterbalanced design. Each trial utilised one of
      four different solutions: 7.5% carbohydrate, 421 mg L(-1) electrolyte (HiC-HiE);
      7.5% carbohydrate, 140 mg L(-1) electrolyte (HiC-LoE); 1.3% carbohydrate, 421 mg
      L(-1) electrolyte (LoC-HiE) and water. Subjects were provided with 50-ml samples
      to ingest and then rate (using a 100-mm line scale) the intensity of sweetness,
      saltiness, thirst-quenching ability and overall liking before (-30 min), during
      (0, 30 and 60 min) and following (90 and 120 min) treadmill running exercise.
      Ratings of sweetness for all energy-containing drinks were higher during exercise
      relative to pre- and post-exercise conditions (P<0.05); ratings also increased
      with duration of exercise (P<0.001). Sweetness ratings for LoC-HiE increased
      during exercise (P<0.05) but remained the same for other beverages. Ratings of
      saltiness decreased for all energy-containing drinks during exercise relative to
      pre-exercise (P<0.05); ratings decreased with duration of exercise in these
      drinks (P<0.05). Ratings of thirst-quenching ability (P=0.039) and overall liking
      (P=0.013) increased with duration of exercise with all beverages. Significant
      changes in sensory perception occur when consuming sports drinks during exercise
      relative to non-exercise conditions. Temporal changes also occur during exercise
      itself which leads to enhanced liking of all beverages.

PMID- 21172369
TI  - A unique immuno-stimulant steroidal sapogenin acid from the roots of Asparagus
      racemosus.
AB  - A new steroidal sapogenin molecule 1 having unique characteristics, 21-nor and
      unusual C19 carboxylic acid has been isolated from the roots of Asparagus
      racemosus. On the basis of chemical evidence, extensive spectroscopic analysis
      including two dimensional (2D) NMR and X-ray studies of single crystal, the
      structure of 1 was determined as (1S,2R,3S,8S,9S,10S,13S,14S,16S,17R,22R,25R)-21
      nor-18beta,27alpha-dimethyl-1beta,2beta,3beta-trihydroxy-25-spirost-4-en-19beta
      oic acid. 1 crystallizes in monoclinic space group P21 with a=9.295(2),
      b=11.238(2), c=11.376(2) A; beta=91.993(4) degrees , Z=2, D(cal)=1.344 Mg/m3. The
      structure was solved by direct methods and refined by full-matrix least-squares
      procedure to a final R-value of 0.0561 for 4064 observed reflections. 1 was
      tested against the type of immune responses generated during treatment in normal
      and immune-suppressed animals and detailed biological activity evaluation
      suggests it to be a potent immunostimulator.

PMID- 21172370
TI  - Disturbance in sex-steroid serum profiles of cattle in response to exogenous
      estradiol: a screening approach to detect forbidden treatments.
AB  - Estradiol benzoate (EB) has been one of the most widely used estrogenic agents in
      animal husbandry, as a way of exogenously introducing the natural hormone
      estradiol-17beta into the animal organism. Estradiol was previously employed to
      induce anabolic effects or reproductive improvements in cattle. However, the
      employment of EB in European countries has been permanently forbidden by
      Directive 2008/97/EC to guarantee consumers' health. Despite this prohibition,
      the control of estradiol-17beta and its esters continues to be a difficult task
      for residue-monitoring plans in European Communities because official analyses of
      natural thresholds for hormones in cattle have not yet been established, leading
      to a lack of confirmation for any exogenous administration of natural hormones.
      Several researchers have worked on excretion profiles of metabolites, variation
      in specific hormonal ratios and metabolomic fingerprints after hormonal
      treatments. This research focuses on the possible existence of disturbances in
      the serum profile of animals treated with EB in terms of steroid sex hormones
      (androgens, oestrogens and progestogens), by investigating the serum levels of
      several of these hormones. The serum samples were collected from three groups of
      cows: one treated with an intramuscular injection of EB, one treated with a
      combination of intravaginal EB and progesterone and a control (non-treated)
      group. The samples have been analysed by a validated high-performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS/MS) method, and 17 natural
      hormones were identified and quantified. Subsequently, data from the serum
      profiles were submitted for statistic and multivariate analysis, and it was
      possible to observe a manifest variation between animal groups. The obtained
      results can help in the development of a viable screening tool for monitoring
      purposes in cattle.

PMID- 21172371
TI  - Differential gene expression profile in the liver of the marine puffer fish
      Takifugu rubripes induced by intramuscular administration of tetrodotoxin.
AB  - Marine puffer fish accumulate a high level of tetrodotoxin (TTX) in the liver and
      ovary, but the underlying mechanism of this toxification is unclear. To elucidate
      the genes related to toxification of the marine puffer fish, we examined the
      hepatic gene expression profile of the marine puffer fish Takifugu rubripes by
      suppression subtractive hybridization in response to the intramuscular
      administration of 0.50 mg TTX/kg body weight into the caudal muscle. The
      accumulation of TTX in the liver reached 68 +/- 4% that of the administered dose
      within 12 h of administration. A total of 1048 clones from the subtracted cDNA
      libraries were successfully sequenced. The nucleotide sequence of 92 of the 1048
      clones was identified as a hepcidin precursor. Reverse transcription-polymerase
      chain reaction experiments revealed that hepcidin precursors were highly
      expressed in the TTX-administered group. In addition, complement C3 (31 clones),
      serotransferrin (30 clones), apolipoprotein A-1 (14 clones), high temperature
      adaptation protein Wap65-2 (14 clones), complement C7 (12 clones), fibrinogen
      beta chain (12 clones), and 70 kDa heat-shock protein 4 (11 clones) were
      obtained. This study confirmed that the intramuscular administration of TTX
      increases the gene expression of the acute-phase response proteins in the liver
      of puffer fish T. rubripes.

PMID- 21172373
TI  - Shape and size discrimination compared.
AB  - Observers presented with pairs of figures differing in area (SIZE) or aspect
      ratio (SHAPE) spontaneously make use of both height and width differences.
      whether or not they are forced to do so by between-interval jittering or even
      instructed to do so. SHAPE discrimination is considerably better than SIZE
      discrimination. The superiority of SHAPE discrimination is probably due to
      partial correlation between the encoding noise of height and width of a figure.
      Discrimination of height differences is seemingly increased (decreased) by
      negatively (positively) correlated width differences, relative to leaving width
      unchanged. This is true whether the different types of trials are presented in
      separate blocks or intermixed. Perhaps SIZE and SHAPE comparisons are always made
      and their decision variables are optimally combined. The difference between SIZE
      and SHAPE discrimination is reduced, if not reversed, when figures are presented
      simultaneously rather than successively. This interaction between type of task
      and mode of presentation, may be due to the increased amount of correlation
      between test and standard figures of the encoding noise common to the two
      dimensions of each figure.

PMID- 21172372
TI  - Diversity of conotoxin types from Conus californicus reflects a diversity of prey
      types and a novel evolutionary history.
AB  - Most species within the genus Conus are considered to be specialists in their
      consumption of prey, typically feeding on molluscs, vermiform invertebrates or
      fish, and employ peptide toxins to immobilize prey. Conus californicus Hinds 1844
      atypically utilizes a wide range of food sources from all three groups. Using DNA
      and protein-based methods, we analyzed the molecular diversity of C.
      californicus toxins and detected a correspondingly large number of conotoxin
      types. We identified cDNAs corresponding to seven known cysteine-frameworks
      containing over 40 individual inferred peptides. Additionally, we found a new
      framework (22) with six predicted peptide examples, along with two forms of a new
      peptide type of unusual length. Analysis of leader sequences allowed assignment
      to known superfamilies in only half of the cases, and several of these showed a
      framework that was not in congruence with the identified superfamily. Mass
      spectrometric examination of chromatographic fractions from whole venom served to
      identify peptides corresponding to a number of cDNAs, in several cases differing
      in their degree of posttranslational modification. This suggests differential or
      incomplete biochemical processing of these peptides. In general, it is difficult
      to fit conotoxins from C. californicus into established toxin classification
      schemes. We hypothesize that the novel structural modifications of individual
      peptides and their encoding genes reflect evolutionary adaptation to prey species
      of an unusually wide range as well as the large phylogenetic distance between C.
      californicus and Indo-Pacific species.

PMID- 21172374
TI  - The molecular basis by which dietary restricted feeding reduces mitochondrial
      reactive oxygen species generation.
AB  - Restricted feeding regimes in rodents that extend longevity lower the rate of
      mitochondrial reactive oxygen species generation. This effect is not dependent
      upon the depression of the state III and IV mitochondrial respiration rates.
      Mitochondria from liver, skeletal muscle and brown adipose tissue adapt to DR
      feeding with a lowered membrane potential that results from an enhanced proton
      leak across the inner membrane. Mitochondrial ROS generation is very sensitive to
      the magnitude of the membrane potential and the enhanced proton leak and ROS
      generation rates are reversible by exogenous insulin in liver and heart
      mitochondria. The adenine nucleotide translocase (ANT) was shown to be the
      dominant proton leak channel induced under DR feeding regimes in these tissues,
      while in brown fat mitochondria, UCP1 was activated, but this was not sensitive
      to exogenous insulin treatment. The effect of DR to modify the proton leak,
      membrane potential and ROS generation rate can be simulated by a range of non
      esterified free fatty acids (NEFA) acting on the ANT to enhance its protonophoric
      activity. Mobilisation of NEFA under DR feeding, when insulin plasma
      concentrations are extremely low, explains the indirect action of insulin to
      counteract the effects of DR feeding on mitochondrial ROS generation.

PMID- 21172375
TI  - Effect of aging and oxidative stress on elongation factor-2 in hypothalamus and
      hypophysis.
AB  - The hypothalamic-hypophysis system (HHS) secretes peptide hormones whose
      synthesis requires the integrity of the translation machinery. As the organisms
      age, a considerable diminution of the protein synthesis takes place in several
      tissues. Among the possible causes of the decline of translation in old animals
      are the modifications of elongation factor-2 (eEF-2). We studied whether the
      level of this protein was affected in the HHS in old animals. The effects of
      aging are compared to those of an oxidant compound (cumene hydroperoxide)
      administered to young rats. The results indicate that oxidative stress could be
      involved in the alterations of eEF-2, which forms adducts with malondialdehyde
      (MDA) and 4-hydroxynonenal (HNE). The alterations of eEF-2 levels, secondary to
      lipid peroxidation and adduct formation with these aldehydes could contribute to
      the suboptimal hormone production from these tissues during aging. Besides eEF-2,
      proteomic analysis shows that several other proteins are affected.

PMID- 21172376
TI  - Delayed focal lipoatrophy after AS03-adjuvanted influenza A (H1N1) 2009 vaccine.
AB  - Intramuscular vaccination may lead to loss of subcutaneous fat resulting in skin
      depression at the site of injection. We report for the first time a delayed
      lipoatrophy after with AS03-adjuvanted influenza A (H1N1) 2009 vaccine.
      Inadequate administration into the adipose tissue may be causative. During next
      pandemic, education to optimal intramuscular administration and prolonged
      monitoring of adverse effects could be proposed.

PMID- 21172377
TI  - Polyfunctional analysis of Gag and Nef specific CD8+ T-cell responses in HIV-1
      infected Indian individuals.
AB  - Polyfunctional CD8+ T-cells have been described as most competent in controlling
      viral replication. We studied the impact of antigen persistence on the
      polyfunctional immune responses of CD8+ T-lymphocytes to HIV Gag and Nef peptides
      and polyclonal stimuli in 40 ART naive HIV infected individuals and analyzed the
      alterations in T-cell functionality in early and late stages of infection.
      Significantly elevated level of global response and polyfunctional profile of
      CD8+ T-cells were observed to polyclonal stimulation, than HIV specific antigens
      in chronically infected individuals. However no key differences were observed in
      CD8+ T-cell functional profile in any of the 15 unique subsets for Gag and Nef
      specific antigens. The subjects in early stage of infection (defined as a gap of
      6 months or less between seroconversion and enrolment and with no apparent
      clinical symptoms) had a higher degree of response functionality (4+ or 3+
      different functions simultaneously) than in the late stage infection (defined as
      time duration since seroconversion greater than 6 months). The data suggest that
      persistence of antigen during chronic infection leads to functional impairment of
      HIV specific responses.

PMID- 21172378
TI  - Single dose of oil-adjuvanted inactivated vaccine protects chickens from lethal
      infections of highly pathogenic H5N1 influenza virus.
AB  - The highly pathogenic H5N1 influenza viruses are endemic in poultry in many
      countries, but continuously infect humans and cause human mortality. H5N1
      influenza viruses have been regarded as a pandemic candidate. In a pandemic event
      by this virus, the protection of poultry with an effective vaccine will help to
      greatly reduce the spread of this virus to humans since it easily infects
      poultry. Here we showed that immunization with one dose of oil-adjuvanted
      inactivated H5N1 vaccine could protect chickens from lethal infection by highly
      pathogenic H5N1 influenza virus until 12 weeks post-immunization. The complete
      protection of chickens depended on the amount of HA antigens in the vaccine.
      Complete homologous protection required over 1.25 MUg of HA antigens and complete
      heterologous protection required over 5.0 MUg of HA antigens. The bivalent H5N1
      inactivated vaccine composed of 1.25 MUg of each antigen from clade 1 and clade
      2.3.4 H5N1 influenza virus completely protected chickens from the lethal
      challenge of both viruses. When we determined the induction of antibody subtypes
      in tissues including nasal cavity, trachea, and lungs, the IgG subtype of
      antibody was induced more than the IgM or IgA subtype of antibody. Taken
      together, our results suggest that one dose of oil-adjuvanted inactivated H5N1
      vaccine could provide chickens with sterile immunity against the homologous
      highly pathogenic H5N1 influenza virus.

PMID- 21172379
TI  - Evaluation of superoxide dismutase from Helicobacter pylori as a protective
      vaccine antigen.
AB  - Helicobacter pylori, the major cause of gastric cancer, have mechanisms that
      allow colonization of the inhospitable gastric mucosa, including enzymes such as
      superoxide dismutase (SOD) which protect against reactive oxygen species. As SOD
      is essential for in vivo colonization, we theorized it might constitute a viable
      vaccine target. H. pylori SOD was expressed in E. coli and a purified recombinant
      protein used to vaccinate mice, prior to live H. pylori challenge. Partial
      protective immunity was induced, similar to that commonly observed with other
      antigens tested previously. This suggests SOD may have utility in a combination
      vaccine comprising several protective antigens.

PMID- 21172380
TI  - Impact of influenza infection on children's hospital admissions during two
      seasons in Athens, Greece.
AB  - A prospective epidemiologic surveillance of hospitalizations associated with
      influenza was conducted in order to calculate population-based hospitalization
      rates. Eligible children were 6 months to 13 years of age and were admitted to
      one of the two large children's hospitals in the Athens area during two influenza
      seasons. Nasopharyngeal aspirates were tested for influenza by a polymerase
      reaction assay. Influenza accounted for 9.9-11.8% of all admissions during the
      influenza season and the overall annual rate of hospitalizations was 13.6-16.8
      cases per 10,000 children being highest for children under 5 years of age (26
      31.2/10,000 children). Febrile seizures and acute otitis media were the two most
      common complications associated with influenza and antibiotics were administered
      to 61% of flu positive patients. Influenza is associated with high
      hospitalization rates among young children and these may be substantially reduced
      with the introduction of routine immunization.

PMID- 21172381
TI  - Antitumor vaccination by Newcastle Disease Virus Hemagglutinin-Neuraminidase
      plasmid DNA application: changes in tumor microenvironment and activation of
      innate anti-tumor immunity.
AB  - A plasmid encoding the Hemagglutinin-Neuraminidase (HN) protein of Newcastle
      Disease Virus (pHN) was tested for its capacity to stimulate innate anti-tumor
      activity in tumor-bearing mice. We observed that application of the pHN plasmid
      at the ear pinna site (i.e.) of mice induces higher levels of systemic interferon
      alpha and reduced tumor growth in the prophylactic mammary carcinoma DA3 tumor
      model in comparison to application of a control plasmid not encoding the HN
      protein. Analysis of the tumor microenvironment revealed a significant increase
      in NK cell infiltration and decrease in infiltration of CD11b(+)Gr-1(high)
      myeloid cells bearing the myeloid-derived suppressor cell (MDSC) phenotype after
      vaccination with the pHN DNA compared to a control DNA. Finally, innate immunity
      and partially type I IFN responses were proved important for the reduction of
      s.c. RMA-S tumor growth after pHN vaccination, as shown with the use of RAG2(-/-)
      and RAG2(-/-)IFNAR1(-/-) mice. These data demonstrate that triggering innate
      immunity by pHN application at the ear pinna of mice modulates the immune cell
      compartment in the tumor microenvironment and reduces tumor growth. This
      highlights thus the potential adjuvant activity of the HN gene in tumor therapy.

PMID- 21172382
TI  - Spontaneous reporting of adverse events following immunisation against pandemic
      influenza in Denmark November 2009-March 2010.
AB  - Our study reviews the spontaneous reports of adverse events following
      immunisation submitted to the Danish Medicines Agency during the 2009-2010
      influenza A/H1N1v season. During the study period (4 November 2009-31 March
      2010), 607 reports comprising 1885 adverse events were reported among 339,507
      influenza A/H1N1v vaccinated individuals (reporting rate, 179 per 100,000
      vaccinated). The majority of individual case safety reports (85%) were submitted
      by physicians and other health care professionals and concerned known and non
      serious reactions occurring within 1 day of vaccination (82%). Events of special
      interest as defined by EMA prior to vaccination campaign start, comprised 1% of
      all events. In conclusion, we did not observe any strong signals of any unknown
      or serious adverse events associated with influenza A/H1N1v vaccination in
      Denmark. Our experience also demonstrates the well-known limitations of
      spontaneous reports with respect to evaluation of a casual relationship and
      highlights the importance for a timely availability of background events rates
      and the need for new approaches to study late adverse effects following
      immunisation.

PMID- 21172383
TI  - The effect of influenza vaccination on risk of acute myocardial infarction: self
      controlled case-series study.
AB  - Acute myocardial infarction (AMI) peaks in winter months, partly linked to
      epidemic influenza. This implies that influenza vaccination may prevent some
      cases of AMI. This study investigated the association between influenza
      vaccination and AMI using the self-controlled case-series method. We identified
      8180 cases of first AMI aged 40 years and over at time of diagnosis. The
      incidence of AMI was significantly reduced in the 60 days following vaccination
      (compared with the baseline period), ranging from a reduction of 32% (IRR 0.68;
      95% CI 0.60-0.78) at 1-14 days after vaccination, to 18% (IRR 0.82; 95% CI 0.75
      0.90) at 29-59 days after vaccination. Reductions in AMI incidence were more
      pronounced for early seasonal vaccinations before mid-November.

PMID- 21172384
TI  - SP-8203 reduces oxidative stress via SOD activity and behavioral deficit in
      cerebral ischemia.
AB  - Both oxidative stress and excessive activation of glutamate receptors are
      implicated as major causes of ischemic brain injury. However, the existing N
      methyl-D-aspartate (NMDA) receptor antagonists have not exerted good clinical
      outcome, most likely because they do not protect neurons against oxidative
      stress. Thus, more effective glutamate antagonists and antioxidants are needed
      for the treatment of ischemic stroke. In previous study, SP-8203, derived from
      earth worms, showed the blocking effect of NMDA receptor. We provided evidence
      that SP-8203 could also suppress the oxidative stress in this study. In vitro,
      250 MUM H2O2 was treated to SH-SY5Y cells after the pre-treatment of SP-8203 (2,
      20 and 200 MUM). SP-8203 significantly suppressed H2O2-induced cell death and
      reactive oxygen species production. In addition, we investigated the effects of
      SP-8203 in middle cerebral artery (MCA) occluded rat model. SP-8203 (5 and 10
      mg/kg) was administered intraperitoneally to rats before and after the MCA
      occlusion and was injected daily for 10 days. After 10 days, SP-8203 remarkably
      reduced brain infarct volume and lipid peroxidation products in the MCA-occluded
      rats but MK-801 didn't. Moreover, SP-8203 significantly improved neurological
      deficits such as shortening of latency time in Rota rod performance. However, MK
      801 didn't improve behavioral deficits. Therefore, SP-8203 may be more effective
      for multiple-target mechanisms of ischemic stroke.

PMID- 21172385
TI  - Mice lacking the galanin gene show decreased sensitivity to nicotine conditioned
      place preference.
AB  - Previous work has indicated that the neuropeptide galanin decreases sensitivity
      to the rewarding effects of morphine and cocaine, but increases alcohol drinking.
      The aim of the current study was to examine the role of galanin signaling in
      nicotine reward by testing the effects of nicotine in mice lacking galanin
      peptide (GAL-/-) as compared to wild-type (GAL+/+) controls. Using an unbiased,
      three-chamber conditioned place preference (CPP) paradigm the dose-response
      function for nicotine CPP was tested in GAL-/- and GAL+/+ mice. Since activation
      of extracellular signal-related kinase (ERK2) is involved in the rewarding
      effects of several classes of drugs of abuse, we then measured the level of ERK2
      phosphorylation in the nucleus accumbens shell (NACsh) and core (NACco) of GAL-/-
      and GAL+/+ mice following re-exposure to the CPP chamber previously paired with
      nicotine as a marker of mesolimbic system activation. Finally, we examined
      whether acute nicotine administration affects ERK2 activity in GAL-/- and GAL+/+
      mice. GAL-/- mice required a higher dose of nicotine to induce a significant CPP
      compared to GAL+/+ mice. In the conditioning groups showing significant
      expression of nicotine CPP, only GAL+/+ mice showed ERK2 activation in the NACsh.
      This suggests that the nicotine CPP observed in GAL+/+ mice resulted in
      differential recruitment of ERK signaling in the NACsh compared to GAL-/- mice.
      In addition, no activation of ERK2 was observed following acute nicotine
      administration in either genotype. These data, along with prior results, suggest
      that galanin alters sensitivity to drugs of abuse differentially, with morphine,
      cocaine and amphetamine place preference suppressed, and nicotine and alcohol
      preference increased, by galanin signaling.

PMID- 21172386
TI  - Targeting the neurovascular unit for treatment of neurological disorders.
AB  - Drug discovery for CNS disorders has been restricted by the inability for
      therapeutic agents to cross the blood-brain barrier (BBB). Moreover, current
      drugs aim to correct neuron cell signaling, thereby neglecting pathophysiological
      changes affecting other cell types of the neurovascular unit (NVU). Components of
      the NVU (pericytes, microglia, astrocytes, and neurons, and basal lamina) act as
      an intricate network to maintain the neuronal homeostatic microenvironment.
      Consequently, disruptions to this intricate cell network lead to neuron
      malfunction and symptoms characteristic of CNS diseases. A lack of understanding
      in NVU signaling cascades may explain why current treatments for CNS diseases are
      not curative. Current therapies treat symptoms by maintaining neuron function.
      Refocusing drug discovery to sustain NVU function may provide a better method of
      treatment by promoting neuron survival. In this review, we will examine current
      therapeutics for common CNS diseases, describe the importance of the NVU in
      cerebral homeostasis and discuss new possible drug targets and technologies that
      aim to improve treatment and drug delivery to the diseased brain.

PMID- 21172388
TI  - Synergistic antitumor effects of Escherichia coli maltose binding protein and
      Bacillus Calmette-Guerin in a mouse lung carcinoma model.
AB  - Maltose binding protein (MBP) is a component of the maltose transport system in
      the periplasm of Escherichia coli. It is commonly believed that MBP has minimal
      effects on the bioactivity, thus, it is widely used in the purification of
      recombinant proteins. Here, we found that the combined immunization with MBP and
      Bacillus Calmette-Guerin (BCG) significantly inhibited tumor growth compared with
      MBP or BCG immunization alone in a mouse lung carcinoma model. Further studies
      showed that MBP nonspecifically activated T helper 1 (Th1) cells and enhanced the
      BCG-induced Th1 cell activation. Moreover, MBP or BCG immunization alone
      increased the activities of natural killer (NK) cells and macrophages, and the
      combined immunization with MBP and BCG induced a synergistic effect on the
      activities of NK cells and macrophages. These results suggest that MBP possesses
      potent immune enhancement activities, and that the combination of MBP and BCG
      induced synergistic antitumor effects might be mediated mainly through the
      activation of Th1 cells, NK cells and macrophages.

PMID- 21172389
TI  - Abbott RealTime HIV-1 m2000rt viral load testing: manual extraction versus the
      automated m2000sp extraction.
AB  - The Abbott RealTime HIV-1 assay is a real-time nucleic acid amplification assay
      available for HIV-1 viral load quantitation. The assay has a platform for
      automated extraction of viral RNA from plasma or dried blood spot samples, and an
      amplification platform with real time fluorescent detection. Overall, this study
      found no clinically relevant differences in viral load, if samples were extracted
      manually.

PMID- 21172387
TI  - Apolipoprotein mimetic peptides: Mechanisms of action as anti-atherogenic agents.
AB  - Apolipoprotein mimetic peptides are short synthetic peptides that share
      structural, as well as biological features of native apolipoproteins. The early
      positive clinical trials of intravenous preparations of apoA-I, the main protein
      component of high density lipoproteins (HDL), have stimulated great interest in
      the use of apolipoprotein mimetic peptides as possible therapeutic agents.
      Currently, there are a wide variety of apolipoprotein mimetic peptides at various
      stages of drug development. These peptides typically have been designed to either
      promote cholesterol efflux or act as anti-oxidants, but they usually exert other
      biological effects, such as anti-inflammatory and anti-thrombotic effects.
      Uncertainty about which of these biological properties is the most important for
      explaining their anti-atherogenic effect is a major unresolved question in the
      field. Structure-function studies relating the in vitro properties of these
      peptides to their ability to reduce atherosclerosis in animal models may uncover
      the best rationale for the design of these peptides and may lead to a better
      understanding of the mechanisms behind the atheroprotective effect of HDL.

PMID- 21172390
TI  - Cell surface targeting of myelin oligodendrocyte glycoprotein (MOG) in the
      absence of endoplasmic reticulum molecular chaperones.
AB  - Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane
      glycoprotein that localizes to myelin sheaths in the central nervous system. MOG
      has important implications in multiple sclerosis, as pathogenic anti-MOG
      antibodies have been detected in the sera of multiple sclerosis patients. As a
      membrane protein, MOG achieves its native structure in the endoplasmic reticulum
      where its folding is expected to be controlled by endoplasmic reticulum
      chaperones. Calnexin, calreticulin, and ERp57 are essential components of the
      endoplasmic reticulum quality control where they assist in the proper folding of
      newly synthesized glycoproteins. In this study, we show that expression of MOG is
      not affected by the absence of the endoplasmic reticulum quality control proteins
      calnexin, calreticulin, or ERp57. We also show that calnexin forms complexes with
      MOG and these interactions might be glycan-independent. Importantly, we show that
      cell surface targeting of MOG is not disrupted in the absence of the endoplasmic
      reticulum chaperones. This article is part of a special issue entitled: 11th
      European Symposium on Calcium.

PMID- 21172391
TI  - The kinesin superfamily protein KIF17 is regulated by the same transcription
      factor (NRF-1) as its cargo NR2B in neurons.
AB  - The kinesin superfamily of motor proteins is known to be ATP-dependent
      transporters of various types of cargoes. In neurons, KIF17 is found to transport
      vesicles containing the N-methyl-D-aspartate receptor NR2B subunit from the cell
      body specifically to the dendrites. These subunits are intimately associated with
      glutamatergic neurotransmission as well as with learning and memory.
      Glutamatergic synapses are highly energy-dependent, and recently we found that
      the same transcription factor, nuclear respiratory factor 1 (NRF-1), co-regulates
      energy metabolism (via its regulation of cytochrome c oxidase and other
      mitochondrial enzymes) and neurochemicals of glutamatergic transmission (NR1,
      NR2B, GluR2, and nNOS). The present study tested our hypothesis that NRF-1 also
      transcriptionally regulates KIF17. By means of in silico analysis,
      electrophoretic mobility shift and supershift assays, in vivo chromatin
      immunoprecipitation assays, promoter mutations, and real-time quantitative PCR,
      we found that NRF-1 (but not NRF-2) functionally regulates Kif17, but not Kif1a,
      gene. NRF-1 binding sites on Kif17 gene are highly conserved among mice, rats,
      and humans. Silencing of NRF-1 with small interference RNA blocked the up
      regulation of Kif17 mRNA and proteins (and of Grin1 and Grin2b) induced by KCl
      mediated depolarization, whereas over-expressing NRF-1 rescued these transcripts
      and proteins from being suppressed by TTX. Thus, NRF-1 co-regulates oxidative
      enzymes that generate energy and neurochemicals that consume energy related to
      glutamatergic neurotransmission, such as KIF17, NR1, and NR2B, thereby ensuring
      that energy production matches energy utilization at the molecular and cellular
      levels.

PMID- 21172392
TI  - Deletion mutant of human cytomegalovirus lacking US2-US6 and US11 maintains MHC
      class I expression and antigen presentation by infected dendritic cells.
AB  - A HCMV mutant of endothelial- and DC-tropic strain TB40/E lacking the described
      MHC downregulating genes US2-6 and US11 (RVTB40/E(4)DeltaUS11) was generated. We
      analyzed the susceptibility of DC to RVTB40/E(4)DeltaUS11 and subsequently
      studied antigen presentation and T-cell stimulation. Wildtype TB40/E- and
      RVTB40/E(4)DeltaUS11 showed no significant difference in the efficiency of
      infection of DC. Whereas infection with TB40/E induced downregulation of MHC I,
      no significant MHC I downregulation was observed on RVTB40/E(4)DeltaUS11-infected
      DC, indicating that the US2-6, US11 region encodes for the major genes relevant
      for MHC I downregulation. However, both viruses induced downregulation of MHC II,
      as well as CD40, CD80, CD86 and CD83 to the same levels. Stimulation of IFN-gamma
      production by HCMV-specific CD8+ T-cells by infected autologous DC correlated
      with the modulation of MHC expression. While TB40/E-infected DC did not
      efficiently stimulate IFN-gamma production, RVTB40/E(4)DeltaUS11-infected DC
      efficiently stimulated CD8+ T-cells to produce IFN-gamma.

PMID- 21172394
TI  - Sex differences in young adults' snack food intake after food commercial
      exposure.
AB  - Exposure to food commercials on television is considered to be related to
      elevated snack food intake in front of the television. However, this assumed
      relation has as yet not been fully established. The present study, therefore
      examined the direct effects of watching television food commercials on concurrent
      non-advertised snack food intake in young adults. In addition, possible sex
      differences were investigated. Participants (N=82, 50% male) watched a movie
      interrupted by two commercial breaks that contained either food commercials or
      neutral commercials. While watching, they could freely eat crisps and chocolate
      coated peanuts. Afterwards, participants filled out questionnaires and were
      weighed and measured. Regression analyses showed that men and women were
      differently affected by the food commercials. Food intake in women was higher
      when they watched the food commercials than when they watched the neutral
      commercials, whereas food intake in men was lower when they watched the food
      commercials than when they watched the neutral commercials. The results suggest
      that especially women are vulnerable for eating more snack food when exposed to
      food commercials.

PMID- 21172393
TI  - Presence and significance of microvesicular steatosis in nonalcoholic fatty liver
      disease.
AB  - BACKGROUND & AIMS: Liver biopsies from patients with nonalcoholic fatty liver
      disease (NAFLD) sometimes exhibit non-zonal aggregates of hepatocytes with
      microvesicular steatosis, but its prevalence and significance are unclear. In
      this study, we have evaluated the frequency of microvesicular steatosis and
      assessed its association with histological markers of disease severity in a large
      sample of NAFLD liver biopsies. METHODS: Liver biopsies from a large cohort of
      adults who participated in two studies conducted by the NASH Clinical Research
      Network (NASH CRN) were included in this cross-sectional study. Liver histology
      was assessed centrally and various histological features scored in a systematic
      fashion. The relationship between microvesicular steatosis and various
      histological features that characterize NAFLD was tested by multiple logistic
      regression, after controlling for age, gender, race, body mass index, and
      diabetes. RESULTS: Among 1022 liver biopsies included, 102 (10%) had
      microvesicular steatosis. No demographic differences were noted between patients
      with or without microvesicular steatosis. The presence of microvesicular
      steatosis was associated with higher grades of steatosis (p<0.001), ballooning
      cell injury (p<0.001), presence of Mallory-Denk bodies (p<0.007), presence of
      megamitochondria (p<0.0001), higher NAS scores (p<0.0001), more advanced fibrosis
      (p<0.0001), and diagnosis of borderline or definite NASH (p<0.0001). CONCLUSIONS:
      Microvesicular steatosis correlates with more advanced histology of NAFLD.
      Longitudinal studies are needed to address the role of microvesicular steatosis
      in mediating cellular injury and disease progression in NAFLD.

PMID- 21172395
TI  - "Watching a person who knows how to cook, you'll learn a lot". Linked lives,
      cultural transmission, and the food choices of Puerto Rican girls.
AB  - In-depth individual interviews were conducted with mainland- and island-dwelling
      Puerto Rican girls (n=23) to determine how migration, acculturation, and family
      contexts influenced food choices. Interview data from girls with diverse
      migration experiences (U.S. mainland raised, recent migrants to U.S. mainland,
      and Puerto Rico raised) were triangulated with extensive participant observation
      conducted in New York State and Puerto Rico. Data analysis using a ground theory
      approach revealed that participants' access to traditional foods varied in three
      domains: mothers' (cultural orientation, health, work, and cooking skills);
      household (composition, presence of Puerto Rican grandmother, and cooking
      skills); and girls' (migration experience, food preferences and values, and
      cooking skills) characteristics. Four food choice types emerged from participant
      narratives that differed in these domains: everybody cooks, tradition keeper,
      seeker, and on my own. Varied language orientations and migration experiences
      were represented among girls across all four food choice types, ranging from
      consistent to limited access to traditional food, demonstrating the limitations
      of one-dimensional models for understanding dietary acculturation. Findings
      demonstrate how a multidimensional, culture-specific model, including both
      cultural and structural characteristics, can influence dietary acculturation at
      the family and household level and food choices among immigrant adolescent girls,
      and guide future research and interventions.

PMID- 21172396
TI  - Black tea improves attention and self-reported alertness.
AB  - Tea has previously been demonstrated to better help sustain alertness throughout
      the day in open-label studies. We investigated whether tea improves attention and
      self-reported alertness in two double-blind, randomised, placebo-controlled,
      crossover studies. Participants received black tea (made from commercially
      available tea bags) in one condition and placebo tea (hot water with food colours
      and flavours) similar in taste and appearance to real tea in the other condition.
      Attention was measured objectively with attention tests (the switch task and the
      intersensory-attention test) and subjectively with a self-report questionnaire
      (Bond-Lader visual analogue scales). In both studies, black tea significantly
      enhanced accuracy on the switch task (study 1 p<.002, study 2 p=.007) and self
      reported alertness on the Bond-Lader questionnaire (study 1 p<.001, study 2
      p=.021). The first study also demonstrated better auditory (p<.001) and visual
      (p=.030) intersensory attention after black tea compared to placebo. Simulation
      of theanine and caffeine plasma time-concentration curves indicated higher levels
      in the first study compared to the second, which supports the finding that tea
      effects on attention were strongest in the first study. Being the second most
      widely consumed beverage in the world after water, tea is a relevant contributor
      to our daily cognitive functioning.

PMID- 21172397
TI  - Safety of high doses of Propionibacterium freudenreichii ET-3 culture in healthy
      adult subjects.
AB  - Propionibacterium freudenreichii ET-3 (7025) culture, a cell-free product of whey
      fermentation by P. freudenreichii ET-3, has been shown to promote the growth of
      Bifidobacteria through the action of 1,4-dihydroxy-2-naphthoic acid (DHNA). Here
      we report the results of two clinical studies designed to evaluate the safety of
      high doses of P. freudenreichii ET-3 culture medium. Study 1 had a randomized,
      double-blind, crossover design. Ten healthy male and four healthy female subjects
      received 45 tablets of either P. freudenreichii ET-3 culture medium (total daily
      intake of 3g solid content and 283.5MUg of DHNA; active group) or placebo
      (unfermented product) during two 1-week supplementation periods separated by a 4
      week washout period. In Study 2, 11 healthy men took four tablets of P.
      freudenreichii ET-3 culture medium per day (total daily intake of 0.267g solid
      content and 22.5MUg of DHNA) for a period of 13weeks. In both studies,
      hematological, clinical chemistry, and urinary parameters were measured before
      and after each supplementation period and gastrointestinal symptoms were assessed
      by questionnaire. In Study 1, there were no statistically significant differences
      between placebo and active supplementation periods in any measured parameter and
      the incidence of gastrointestinal symptoms were similar between groups. In Study
      2, total protein, white blood cell count, hemoglobin, and mean corpuscular
      hemoglobin concentration decreased significantly from baseline and mean
      corpuscular volume and urine pH increased from baseline. The changes in
      hematological parameters were deemed not to be due to P. freudenreichii ET-3
      culture medium supplementation given that all parameters remained within normal
      ranges and were not consistent with any clinically meaningful effect.

PMID- 21172398
TI  - Structural requirements for mutation formation from polycyclic aromatic
      hydrocarbon dihydrodiol epoxides in their interaction with food chemopreventive
      compounds.
AB  - Chinese hamster V79 cells were used to investigate the protective effect of four
      known antimutagens present in food, chlorophyllin (CHL), ellagic acid (EA),
      epigallocathechingallate (EGCG) and benzylisothiocyanate (BITC), against potent
      mutagenic polycyclic aromatic hydrocarbon diol epoxides (PAH-DE) derived from
      benzo[a]pyrene (BP), dibenzo[a,h]anthracene (DBA), dibenzo[a,l]pyrene (DBP), and
      benzo[c]phenanthrene (BPh) known to be deposited on crops from polluted ambient
      air or formed during food processing. As fjord-region PAH-DE are more toxic and
      mutagenic than bay-region PAH-DE, we adjusted the concentrations of PAH-DE to
      induce approximately the same levels of adducts. The studies were performed using
      an assay indicating toxicity in terms of reduced cell proliferation together with
      the V79 Hprt assay for monitoring mutant frequencies. CHL significantly increased
      the survival and showed a protective effect against the mutagenicity of all PAH
      DE. A significant protective effect of EA was found towards the mutagenicity of
      BPDE, DBPDE and BPhDE and with EGCG for BPDE and BPhDE. BITC had a slight
      positive effect on the mutagenicity of DBADE and BPhDE. Taken together, a novel
      and unexpected finding was that the antimutagenic activity could differ as much
      as by a factor of 7 towards four carcinogenic PAH metabolites being relatively
      similar in structure and genotoxic activity.

PMID- 21172399
TI  - Effect of gallic acid on xenobiotic metabolizing enzymes in 1,2-dimethyl
      hydrazine induced colon carcinogenesis in Wistar rats--a chemopreventive
      approach.
AB  - Colon cancer risk may be influenced by phase I and II xenobiotic-metabolizing
      enzyme systems. The chemopreventive agent gallic acid (GA), a plant polyphenol,
      is found in various natural products. Our aim was to evaluate the potential role
      of GA on drug-metabolizing enzymes in 1,2-dimethyl hydrazine (DMH) induced rat
      colon carcinogenesis. The total experimental duration was 30 weeks. The effect of
      GA (50 mg/kg b.w.) on the activities of phase I enzymes (cytochrome P450 and
      cytochrome b5) and phase II enzymes (glutathione S-transferase, DT-diaphorase and
      gamma glutamyl transpeptidase) were assessed in the liver and colonic mucosa and
      the colons were also examined visually. In DMH induced rats, there was a decrease
      in the activities of phase II enzymes and an increase in the activities of phase
      I enzymes. On GA supplementation, there was a significant increase in the
      activities of phase II enzymes and a significant decrease in the activities of
      phase I enzymes, in addition to the decreased tumor incidence. Histopathological
      changes also confirm this. Thus, the marked potential of GA in modulating the
      phase I and II xenobiotic-metabolizing enzymes suggests that GA may have a major
      impact on colon cancer chemoprevention.

PMID- 21172400
TI  - Betulin and betulinic acid attenuate ethanol-induced liver stellate cell
      activation by inhibiting reactive oxygen species (ROS), cytokine (TNF-alpha, TGF
      beta) production and by influencing intracellular signaling.
AB  - BACKGROUND/AIMS: Liver fibrosis has been reported to be inhibited in vivo by
      oleanolic and ursolic acids. However, the mechanisms of the action of those
      triterpenoids are poorly understood. In this study, we aimed to determine the
      antifibrotic potential of other triterpenes, betulin and betulinic acid, and to
      characterize their influence on the signal transduction pathways involved in
      ethanol-activated hepatic stellate cells (HSCs). METHODS: Investigated was the
      influence of preincubation of rat HSCs with betulin and betulinic acid, at non
      toxic concentrations, on ethanol-induced toxicity, migration, and several markers
      of HSC activation such as smooth muscle alpha-actin (alpha-SMA) and procollagen I
      expression, release of reactive oxygen species (ROS) and cytokines: tumor
      necrosis factor-alpha (TNF-alpha) and tumor growth factor-beta1 (TGF-beta1), and
      production of metalloproteinase-2 (MMP-2) and tissue inhibitors of
      metalloproteinases (TIMP-1 and TIMP-2). To assess the mechanism of the action of
      those triterpenes, intracellular signals such as nuclear factor-kappaB
      (NFkappaB), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein
      kinase (p38 MAPK) induced by ethanol were examined. RESULTS: In vitro, betulin,
      but not betulinic acid, protected HSCs against ethanol toxicity. However, both
      betulin and betulinic acid inhibited the production of ROS by HSCs treated with
      ethanol and inhibited their migration as well as ethanol-induced TNF-alpha, and
      TGF-beta1, production. Betulin and betulinic acid down-regulated ethanol-induced
      production of TIMP-1 and TIMP-2. Betulin and betulinic acid, also decreased
      ethanol-induced activity of MMP-2. In ethanol-induced HSCs, betulin inhibited the
      activation of the p38 MAPK and the JNK transduction pathways, while betulinic
      acid inhibited the JNK transduction pathway only. They also significantly
      inhibited phosphorylation of IkappaB and Smad 3 and attenuated the activation of
      TGF-beta1 and NFkappaB/IkappaB transduction signaling. CONCLUSION: The results
      indicated that betulin and betulinic acid inhibited ethanol-induced activation of
      HSCs on different levels, acting as antioxidants, inhibitors of cytokine
      production, and inhibitors of TGF-beta, and NFkappaB/IkappaB transduction
      signaling. Betulin was also inhibitor of both JNK and p38 MAPK signal
      transduction, while betulinic acid inhibited only JNK. The remarkable inhibition
      of several markers of HCS activation makes triterpenes, especially betulin,
      promising agents for anti-fibrotic combination therapies.

PMID- 21172401
TI  - Cross-resistance of cadmium-resistant cells to manganese is associated with
      reduced accumulation of both cadmium and manganese.
AB  - The mechanism of cellular entry of cadmium remains unclear. We have previously
      established cadmium-resistant cells from mouse embryonic cells of metallothionein
      (MT)-null mice, and demonstrated that the down-regulation of a zinc transporter,
      Zrt/Irt-related protein (ZIP) 8, was responsible for the reduced cadmium
      incorporation into cells. In the present study, we developed cadmium-resistant
      cells (A+70 and B+70) from mouse embryonic cells of MT-expressing wild-type mice.
      The LC50 values of CdCl2 for A+70 and B+70 cells were about 200 MUM while that of
      the parental cells was 30 MUM. We found that the cadmium resistance of these
      cells was conferred not only by enhanced expression of MT, but also by a decrease
      in cadmium accumulation. Since the uptake rates of cadmium into A+70 and B+70
      cells were lowered, we determined the expression levels of the metal transporters
      and channels potentially involved in the cellular uptake of cadmium. We found a
      down-regulation of multiple transport systems, including ZIP8, divalent metal
      transporter 1 (DMT1), and alpha1 subunits of L-type (Ca(V)1.2) and T-type
      (Ca(V)3.1) voltage-dependent calcium channels, in A+70 and B+70 cells.
      Furthermore, A+70 and B+70 cells exhibited cross-resistance to cytotoxicity of
      MnCl2, probably due to a marked decrease in manganese uptake in these cells.
      These results suggest that the suppressed expression of ZIP8 and DMT1, which are
      known to have affinities for both cadmium and manganese, may be responsible for
      the reduction in the uptake, and consequently the cytotoxicity, of cadmium and
      manganese in A+70 and B+70 cells.

PMID- 21172402
TI  - Effect of caries infiltration technique and fluoride therapy on the colour
      masking of white spot lesions.
AB  - OBJECTIVES: A carious lesion is initiated through the subsurface demineralization
      of enamel, and presents clinically as a white spot, interfering with the
      aesthetics. This lesion should not receive restorative treatment because it is
      capable of remineralization. The aim of this study was to evaluate the
      performance of different treatments on masking white spot lesions by assessing
      the colour change. METHODS: Artificial white spot lesions were produced in bovine
      enamel of 60 cylindrical-shaped samples. The samples were randomly divided into
      four groups: CON (control) - immersion in artificial saliva; DF - daily
      application of 0.05% fluoride solution; WF - weekly application of 2% fluoride
      gel; and IC - resin infiltration (Icon((r)) - DMG). The assessment of colour was
      performed by a spectrophotometer in four distinct stages: baseline, after the
      production of artificial caries; after 4 weeks; after 8 weeks; and after a new
      acid challenge. The DeltaL values were calculated at each stage in relation to
      the baseline colour. RESULTS: The application of RM ANOVA revealed significant
      differences between the factors' treatment and time (p=0.001). For the
      interaction between factors there were no significant differences (p=0.27). The
      Tukey's test (p<0.05) was then applied and showed that the specimens treated with
      Icon((r)) exhibited the lowest means, followed by Group DF, Group CON, and Group
      WF, in that order. CONCLUSION: Resin infiltration was proven to be an effective
      treatment for masking white spot lesions. Also, after a new acid challenge, the
      group infiltrated with low viscosity resin presented the lowest means of colour
      change.

PMID- 21172403
TI  - Cloning and characterisation of novel cystatins from elapid snake venom glands.
AB  - Snake venoms contain a complex mixture of polypeptides that modulate prey
      homeostatic mechanisms through highly specific and targeted interactions. In this
      study we have identified and characterised cystatin-like cysteine-protease
      inhibitors from elapid snake venoms for the first time. Novel cystatin sequences
      were cloned from 12 of 13 elapid snake venom glands and the protein was detected,
      albeit at very low levels, in a total of 22 venoms. One highly conserved isoform,
      which displayed close sequence identity with family 2 cystatins, was detected in
      each elapid snake. Crude Austrelaps superbus (Australian lowland copperhead)
      snake venom inhibited papain, and a recombinant form of A. superbus cystatin
      inhibited cathepsin L ? papain > cathepsin B, with no inhibition observed for
      calpain or legumain. While snake venom cystatins have truncated N-termini,
      sequence alignment and structural modelling suggested that the evolutionarily
      conserved Gly-11 of family 2 cystatins, essential for cysteine protease
      inhibition, is conserved in snake venom cystatins as Gly-3. This was confirmed by
      mutagenesis at the Gly-3 site, which increased the dissociation constant for
      papain by 10(4)-fold. These data demonstrate that elapid snake venom cystatins
      are novel members of the type 2 family. The widespread, low level expression of
      type 2 cystatins in snake venom, as well as the presence of only one highly
      conserved isoform in each species, imply essential housekeeping or regulatory
      roles for these proteins.

PMID- 21172404
TI  - GATA4 regulates Sertoli cell function and fertility in adult male mice.
AB  - Transcription factor GATA4 is expressed in Sertoli and Leydig cells and is
      required for proper development of the murine fetal testis. The role of GATA4 in
      adult testicular function, however, has remained unclear due to prenatal
      lethality of mice harboring homozygous mutations in Gata4. To characterize the
      function of GATA4 in the adult testis, we generated mice in which Gata4 was
      conditionally deleted in Sertoli cells using Cre-LoxP recombination with Amhr2
      Cre. Conditional knockout (cKO) mice developed age-dependent testicular atrophy
      and loss of fertility, which coincided with decreases in the quantity and
      motility of sperm. Histological analysis demonstrated Sertoli cell vacuolation,
      impaired spermatogenesis, and increased permeability of the blood-testis barrier.
      RT-PCR analysis of cKO testes showed decreased expression of germ cell markers
      and increased expression of testicular injury markers. Our findings support the
      premise that GATA4 is a key transcriptional regulator of Sertoli cell function in
      adult mice.

PMID- 21172406
TI  - Cannabidiol decreases body weight gain in rats: involvement of CB2 receptors.
AB  - Cannabidiol (CBD) is a major non-psychotropic constituent of Cannabis sativa,
      with well recognized therapeutic potential. Considering the importance of the
      endogenous cannabinoid system to the regulation of food intake and energy balance
      we studied the effects of repeated CBD administration on body weight gains in
      rats. Male Wistar rats (260 +/- 20 g at start of study) received intraperitoneal
      injections of CBD at doses of 2.5 and 5mg/kg/day for 14 consecutive days and body
      weight gains were monitored. Both doses of CBD produced significant decrease in
      body weight gain, with the effect produced by 5mg/kg being more pronounced. The
      CB2 receptor selective antagonist, AM630, blocked the decrease in body weight
      gain. AM630 alone did not affect body weight gain. The results suggest that CBD
      has the ability to alter body weight gain, possibly via the CB2 receptor. CB2
      receptors may play a role in the regulation of body weight and the effects of CB2
      specific ligands should be further investigated in studies of body weight
      regulation.

PMID- 21172405
TI  - Acamprosate reduces ethanol drinking behaviors and alters the metabolite profile
      in mice lacking ENT1.
AB  - Acamprosate is clinically used to treat alcoholism. However, the precise
      molecular functionality of acamprosate in the central nervous system remains
      unclear, although it is known to antagonize glutamate action in the brain. Since
      elevated glutamate signaling, especially in the nucleus accumbens (NAc), is
      implicated in several aspects of alcoholism, we utilized mice lacking type 1
      equilibrative nucleoside transporter (ENT1), which exhibit increased glutamate
      levels in the NAc as well as increased ethanol drinking behaviors. We found that
      acamprosate significantly reduced ethanol drinking of mice lacking ENT1 (ENT1(-/
      )) while having no such effect in wild-type littermates. We then analyzed the
      basal and acamprosate-treated accumbal metabolite profiles of ENT1(-/-) and wild
      type mice using in vivo 16.4T proton magnetic resonance spectroscopy (MRS). Our
      data show that basal glutamate+glutamine (Glx), glutamate, glutamine and N
      acetylaspartatic acid (NAA) levels are increased in the nucleus accumbens (NAc)
      of ENT1(-/-) compared to wild-type mice. We then found that acamprosate treatment
      significantly reduced Glx and glutamine levels while increasing taurine levels in
      the NAc of only ENT1(-/-) compared to their saline-treated group while
      normalizing other metabolite compared to wild-type mice. This study will be
      useful in the understanding of the molecular basis of acamprosate in the brain.

PMID- 21172407
TI  - Enhanced responsivity of 5-HT(2A) receptors at warm ambient temperatures is
      responsible for the augmentation of the 1-(2,5-dimethoxy-4-iodophenyl)-2
      aminopropane (DOI)-induced hyperthermia.
AB  - Warm ambient temperature facilitates hyperthermia and other neurotoxic responses
      elicited by psychogenic drugs such as MDMA and methamphetamine. However, little
      is known about the neural mechanism underlying such effects. In the present
      study, we tested the hypothesis that a warm ambient temperature may enhance the
      responsivity of 5-HT(2A) receptors in the central nervous system and thereafter
      cause an augmented response to 5-HT(2A) receptor agonists. This hypothesis was
      tested by measuring changes in body-core temperature in response to the 5-HT(2A)
      receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) administered
      at four different ambient temperature levels: 12  degrees C (cold), 22  degrees C
      (standard), 27  degrees C (thermoneutral zone) and 32  degrees C (warm). It was
      found that DOI only evoked a small increase in body-core temperature at the
      standard (22  degrees C) or thermoneutral ambient temperature (27  degrees C). In
      contrast, there was a large increase in body-core temperature when the
      experiments were conducted at the warmer ambient temperature (32  degrees C).
      Interestingly, the effect of DOI at the cold ambient temperature of 12  degrees C
      was significantly reduced. Moreover, the ambient temperature-dependent response
      to DOI was completely blocked by pretreatment with the 5-HT(2A) receptor
      antagonist ketanserin. Taken together, these findings support the hypothesis that
      5-HT(2A) receptors may be responsible for some neurotoxic effects of psychogenic
      drugs in the central nervous system, the activity of which is functionally
      inhibited at cold but enhanced at warm ambient temperature in contrast to that at
      standard experimental conditions.

PMID- 21172408
TI  - Differences in the fractional abundances of carbohydrates of natural and
      recombinant human tissue factor.
AB  - BACKGROUND: Tissue factor (TF) is a single polypeptide integral membrane
      glycoprotein composed of 263 residues and is essential to life in its role as the
      initiator of blood coagulation. Previously we have shown that the activity of the
      natural placental TF (pTF) and the recombinant TF (rTF) from Sf9 insect cells is
      different (Krudysz-Amblo, J. et al (2010) J. Biol. Chem. 285, 3371-3382).
      METHODS: In this study, using mass spectrometry, we show by quantitative analysis
      that the extent of glycosylation varies on each protein. RESULTS AND CONCLUSIONS:
      Fractional abundance of each glycan composition at each of the three
      glycosylation sites reveals the most pronounced difference to be at asparagine
      (Asn) 11. This residue is located in the region of extensive TF-factor VIIa
      (FVIIa) interaction. Carbohydrate fractional abundance at Asn11 revealed that
      glycosylation in the natural placental TF is much more prevalent (~76%) than in
      the recombinant protein (~20%). The extent of glycosylation on Asn124 and Asn137
      is similar in the two proteins, despite the pronounced differences in the
      carbohydrate composition. Additionally, 77% of rTF exists as TF des-1, 2 (missing
      the first two amino acids from the N-terminus). In contrast, only 31% of pTF is
      found in the des-1, 2 form. CONCLUSION: These observations may attribute to the
      difference in the ability of TF-FVIIa complex to activate factor X (FX). GENERAL
      SIGNIFICANCE: Structural and functional comparison of the recombinant and natural
      protein advances our understanding and knowledge on the biological activity of
      TF.

PMID- 21172409
TI  - Protective effect of trifluoperazine on hydrogen peroxide-induced apoptosis in
      PC12 cells.
AB  - This study investigated effects of trifluoperazine (TFP) against the cytotoxicity
      induced by H2O2 in PC12 cells and the mechanisms thereof. Different
      concentrations of H2O2 (100-500 MUM) induced a significant decrease in cell
      viability accompanied by increased oxidative stress and cell apoptosis.
      Pretreatment with TFP inhibited H2O2-induced cell viability loss. The flow
      cytometric assay showed that TFP can inhibit intracellular reactive oxygen
      species (ROS) generation and reduce the cell apoptosis. The electrophysiological
      recordings indicated that when treated with H2O2, the calcium current was
      significantly increased. Pretreatment with TFP increased mitochondrial membrane
      potential (MMP) in cells of oxidative injury. These results suggested that TFP
      can reduce apoptosis by inhibiting ROS generation and preventing loss of MMP in
      cells. Meanwhile, the protective effect of TFP on the cell apoptosis may be
      related to the calcium overload. TFP may inhibit the calcium overload process to
      achieve the protection against apoptosis.

PMID- 21172410
TI  - Repeated extinction and reversal learning of an approach response supports an
      arousal-mediated learning model.
AB  - We assessed the effects of repeated extinction and reversals of two conditional
      stimuli (CS+/CS-) on an appetitive conditioned approach response in rats. Three
      results were observed that could not be accounted for by a simple linear operator
      model such as the one proposed by Rescorla and Wagner (1972): (1) responding to a
      CS- declined faster when a CS+ was simultaneously extinguished; (2) reacquisition
      of pre-extinction performance recovered rapidly within one session; and (3)
      reversal of CS+/CS- contingencies resulted in a more rapid recovery to the
      current CS- (former CS+) than the current CS+, accompanied by a slower
      acquisition of performance to the current CS+. An arousal parameter that mediates
      learning was introduced to a linear operator model to account for these effects.
      The arousal-mediated learning model adequately fit the data and predicted data
      from a second experiment with different rats in which only repeated reversals of
      CS+/CS- were assessed. According to this arousal-mediated learning model,
      learning is accelerated by US-elicited arousal and it slows down in the absence
      of US. Because arousal varies faster than conditioning, the model accounts for
      the decline in responding during extinction mainly through a reduction in
      arousal, not a change in learning. By preserving learning during extinction, the
      model is able to account for relapse effects like rapid reacquisition, renewal,
      and reinstatement.

PMID- 21172411
TI  - Serum cardiac troponin I concentrations transiently increase in rats given
      rosiglitazone.
AB  - Rosiglitazone, a peroxisome proliferator-activated receptor gamma (PPARgamma)
      agonist of the thiazolidinedione class, is a major insulin-sensitizing drug
      widely used to treat type-2 diabetes. Rosiglitazone causes myocardial hypertrophy
      in rodents and increases the risk of cardiac events in man. To better
      characterize its cardiac effects, male Wistar rats were orally administered 0, 10
      or 80 mg/kg/day rosiglitazone. Myocardial gene expression profiling, hematology,
      histopathology and clinical chemistry, including measurement of serum cardiac
      troponin (cTn) I concentration with the ultrasensitive assay, were evaluated
      after 6 and 24h and 7 and 14 days of dosing. Heart weight was increased 10% after
      7 days and 16% after 14 days of dosing at 80 mg/kg/day in the absence of
      microscopic changes. At the transcriptomic level, the number of differentially
      expressed probes was small: it was most at 24h in rats given 80 mg/kg
      rosiglitazone with 356 differentially regulated probes (fold change >1.3 fold,
      p<0.05). Also, gene categories typically associated with myocardial damage were
      not over-represented. Most importantly, serum cTnI concentrations in 5/9 rats
      after 7 days of dosing at 80 mg/kg/day were above the upper limit of serum cTnI
      concentration. cTnI concentrations after 14 days of dosing were similar between
      rats given the vehicle and rosiglitazone at 80 mg/kg. This is the first study to
      detect increases of serum cTnI concentrations in rats administered rosiglitazone.
      In light of reported cardiac events in patients chronically dosed with PPARgamma
      agonists, our results support serum cTnI concentrations as an early biomarker of
      cardiac liability.

PMID- 21172412
TI  - Sulfur mustard induced oxidative stress and its alteration by epigallocatechin
      gallate.
AB  - Sulfur mustard (bis(2-chloroethyl)sulfide; CAS: 505-60-2; abbreviated as HD) is a
      chemical warfare agent with not well understood mechanism of toxic effect.
      Deprivation of energy in cells and arising of oxidative stress appears during the
      exposure. Our experiment is based on investigation of 10mg or 20mg
      epigallocatechin gallate (EGCG) dose prophylactic effect (1h before HD) in rats
      exposed to either 20mg or 80 mg of HD. Blood mass, plasma and liver were sampled.
      Ferric reducing antioxidant power (FRAP), reduced glutathione, thiobarbuturic
      acid reactive substances (TBARSs), glutathione reductase, glutathione S
      transferase and caspase 3 were assessed. Animals were sacrificed one day after
      exposure. We found significant deprivation of low molecular weight antioxidants
      due to EGCG but not due to HD. However, HD depleted reduced glutathione. EGCG has
      no effect to influence TBARS level. EGCG and HD up-regulated glutathione
      reductase and EGCG down regulated glutathione S-transferase in liver tissue.
      Regarding caspase, EGCG had anti apoptotic potency. We discuss potency to use
      EGCG to ameliorate redox balance after HD exposure. The data also appoints at
      difficulty in antioxidant therapy as prophylaxis to the oxidative stress related
      toxins exposure and ambivalent modulation of oxidative stress.

PMID- 21172413
TI  - The neuroprotective effect of modified Yeoldahanso-tang via autophagy enhancement
      in models of Parkinson's disease.
AB  - AIM OF STUDY: Modified Yeoldahanso-tang (MYH) is a Korean herbal formula,
      containing 10 herbs: Pueraria lobata (Willd.) Ohwi, Angelica tenuissima Nakai,
      Scutellaria baicalensis Georgi, Platycodon grandiflorum (Jacq), Angelicae
      Dahurica, Cimicifuga heracleifolia Kom, Raphanus sativa L., Polygala tenuifolia
      (Willd.), Acorus gramineus Soland. and Dimocarpus longan Lour. The constitutive
      ratio of the ten herbs is at 6:4:2:1:2:2:2:4:6:6 in dry weight. MYH has been used
      to treat amnesia, hypochondria and dementia in Korea. In this study, we explored
      the possibility of using MYH in the prevention and treatment of Parkinson's
      disease (PD). Specifically, we made an effort to demonstrate the neuroprotective
      effects of MYH using experimental methods similar to those used in a recent study
      of PD. MATERIALS AND METHODS: 1-Methyl-4-phenylpyridinium (MPP+) (400MUM) was
      used to induce cytotoxicity in NGF (nerve growth factor)-differentiated PC12
      cells. Cell viability was measured using a MTT assay. Induction of autophagy by
      MYH in NGF-differentiated PC12 cells was measured using an immunoblotting assay
      with LC3 and beclin 1 antibodies. The proteasomal inhibitor lactacystin (10MUM)
      was used to cause UPS dysfunction in NGF-differentiated PC12 cells. Clearance of
      aggregated proteins by MYH was measured using an immunoblotting assay with an
      ubiquitin antibody. 1-Methyl-4-phenyl-1,2,3,6-tetrahydrophenylpyridine (MPTP)
      (20mg/kg, 4 times i.p.) caused substantia nigra injuries in C57BL/6 mice.
      Dopamine (DA) neurons were identified using a tyrosine hydroxylase
      immunohistochemistry (TH-IHC) assay with a rabbit anti-TH antibody. RESULTS: Our
      findings indicate that MYH provides protection against MPP+-induced injury in NGF
      differentiated PC12 cell. And MYH provides neuroprotection against lactacystin
      induced NGF-differentiated PC12 cell death, which effect is partially mediated by
      autophagy enhancement through enhanced degradation of aggregated proteins.
      Additionally, in a C57BL/6 mice model with MPTP-induced substantia nigra
      injuries, MYH inhibits both the loss of TH-positive neurons in the substantia
      nigra pars compacta (SNpc) and the reduction of the optical density of TH-IR
      fibers in the striatum (ST). CONCLUSIONS: All of our results indicate that MYH
      treatment has neuroprotective effects that are partially mediated by autophagy
      enhancement. MYH may be a promising herbal formula for the prevention and
      treatment of neurodegenerative diseases, especially PD.

PMID- 21172414
TI  - Why do patients with psychosis use cannabis and are they ready to change their
      use?
AB  - Numerous studies have shown that patients with psychosis are more likely to use
      illicit drugs than the general population, with cannabis being the most popular.
      There exists overwhelming evidence that cannabis use can contribute to the onset
      of schizophrenia and poor outcome in patients with established psychosis.
      Therefore, understanding why patients use cannabis and whether they are motivated
      to change their habits is important. The evidence is that patients with psychosis
      use cannabis for the same reasons the general population does, to 'get high',
      relax and have fun. There is little support for the 'self-medication' hypothesis,
      while the literature points more towards an 'alleviation of dysphoria' model.
      There is a lack of research reporting on whether psychotic patients are ready to
      change their use of cannabis, which has obvious implications for identifying
      which treatment strategies are likely to be effective.

PMID- 21172415
TI  - Genomic comparisons of USA300 Staphylococcus aureus colonizating the nose and
      rectum of children with skin abscesses.
AB  - USA300 Staphylococcus aureus is responsible for the current outbreak of skin
      abscesses in the United States. Unlike other USA types, USA300 colonizes the
      rectum at rates higher than the nose. The reason for the difference in
      colonization site preference may be related to specific adherence or attachment
      factors contained in the genome of these strains. Additional knowledge in this
      field may help design novel prophylactic and therapeutic strategies to combat
      staphylococcal infections. Strains of USA300 MSSA and MRSA colonizing the nose
      and/or rectum from children with staphylococcal skin abscesses were compared by
      whole genome array technology to identify bacterial genetic determinants
      associated with site-specific colonization. Strains isolated from different
      colonization sites were indistinguishable by genomic content. Site-specific
      colonization traits were not detected in the colonizing bacteria by this array.
      Either host characteristics associated with staphylococcal carriage or under
      represented bacterial genomic constructions need to be examined to determine the
      etiology of this site-specific colonization.

PMID- 21172417
TI  - Yeast Saccharomyces cerevisiae devoid of Cu,Zn-superoxide dismutase as a cellular
      model to study acrylamide toxicity.
AB  - Acrylamide is known as a cytotoxic and genotoxic component of starch-containing
      heat-processed food. We demonstrate that yeast Saccharomyces cerevisiae may be
      used as a cellular model to examine the biochemical mechanisms of acrylamide
      toxicity. We found that acrylamide causes impairment of growth of the yeast
      deficient in Cu,Zn-superoxide dismutase (Deltasod1) in a concentration-dependent
      manner. This growth inhibitory effect is not due to cell death but to decreased
      cell vitality and proliferative capacity. Treatment of the Deltasod1 yeast with
      acrylamide induced generation of increased reactive oxygen species and depletion
      of glutathione. The toxicity of acrylamide for yeast cells may be abolished by
      antioxidants (ascorbate, cysteine, N-acetylcysteine, glutathione and
      dithiothreitol) or lowering oxygen content in the atmosphere.

PMID- 21172416
TI  - Identification and dissection of the Nrf2 mediated oxidative stress pathway in
      human renal proximal tubule toxicity.
AB  - The identification and dissection of cellular stress mechanisms is fundamental to
      understanding the susceptibility of the kidney to chemicals and pharmaceuticals
      and for the development of renal biomarkers indicative of sub lethal injury.
      Here, we utilised whole genome DNA microarrays in an attempt to uncover molecular
      mechanisms of response to nephrotoxin exposure. Human renal proximal tubular
      cells (HK-2) were treated for 12h and 48 h with 5 MUM Cadmium (Cd), 30 MUM Diquat
      Dibromide (Diq), and 5 MUM Cyclosporine A (CsA). Nephrotoxin treatment resulted
      in an alteration of a total of 4608 transcripts. Ingenuity Pathways AnalysisTM
      revealed the anti-oxidant and detoxification Nrf2 pathway as the most
      significantly enriched signaling pathway in the selected dataset. Activation of
      this transcription factor was confirmed as nuclear translocation and paralleled
      the temporal alterations of compound induced H(2)O(2) production.
      Transcriptomics, western blot and immunofluorescence showed an induction of both
      HO-1 and NQO1 with Cd and Diq exposure, but not with CsA treatment. Knockdown of
      Nrf2 by siRNA, reduced compound induced NQO1 mRNA to basal levels and attenuated
      toxin induced HO-1 mRNA expression. siRNA knock down of HO-1, but not NQO1,
      enhanced Cd induced H(2)O(2) production and Cd induced toxicity. Using an un
      biased transcriptomic approach we have identified the Nrf2 pathway as the most
      significant signaling response in renal epithelial cells challenged with
      nephrotoxin. This study highlights the importance of this pathway and
      particularly HO-1 in renal epithelial adaptation to oxidative stress.

PMID- 21172418
TI  - Ocular irritation reversibility assessment for personal care products using a
      porcine corneal culture assay.
AB  - Personal care product manufacturers have used a broad spectrum of alternative
      ocular irritation assays during the past two decades because these tests do not
      require the use of live animals, they provide reliable predictive data, and they
      are relatively inexpensive to conduct. To complement these assays, the ex vivo
      Porcine Corneal Opacity Reversibility Assay (PorCORA) was recently developed
      using a corneal culture model to predict reversibility of ocular irritants. Three
      commercially available consumer products (a shampoo, a hair color glaze, and a
      hair colorant system containing 12% hydrogen peroxide) were each tested in two
      PorCORA study replicates in order to assess potential ocular damage reversibility
      for surfactant-, propylene carbonate-, and peroxide-based formulations,
      respectively. Under the exaggerated, in vitro study conditions, the surfactant
      based shampoo may cause irreversible porcine corneal damage (histological changes
      in the epithelial squamous cell and/or basal cell layers), whereas the hair color
      glaze and 12% hydrogen peroxide product caused fully reversible ocular irritation
      (microscopic changes only in the superficial squamous cell layer). The hair color
      glaze and peroxide product results correlate with established in vivo data for
      similar compounds, but the shampoo results contradicted previous BCOP results
      (expected to be only a mild irritant). Therefore, although the PorCORA protocol
      shows promise in predicting the extent and reversibility of potential ocular
      damage caused by accidental consumer eye exposure to personal care products, the
      contradictory results for the surfactant-based shampoo indicate that more
      extensive validation testing of the PorCORA is necessary to definitively
      establish the protocol's reliability as a Draize test replacement.

PMID- 21172419
TI  - Caloric restriction attenuates age-related changes of DNA methyltransferase 3a in
      mouse hippocampus.
AB  - Recent studies have suggested that DNA methylation is implicated in age-related
      changes in gene expression as well as in cognition. DNA methyltransferase 3a
      (Dnmt3a), which catalyzes DNA methylation, is essential for memory formation and
      underlying changes in neuronal and synaptic plasticity. Because caloric
      restriction (CR) and upregulation of antioxidants have been suggested as
      strategies to attenuate age-related alterations in the brain, we hypothesized
      that both a diet restricted in calories and transgenic overexpression of normal
      human Cu/Zn superoxide dismutase 1 (SOD) attenuate age-related changes in Dnmt3a
      in the aging mouse hippocampus. For this purpose, we performed qualitative and
      quantitative analyses of Dnmt3a-immunoreactivity (IR) for the hippocampal dentate
      gyrus (DG), CA3 and CA1-2 regions in 12- and 24-month-old mice from 4 groups,
      i.e. (1) wild-type (WT) mice on a control diet (WT-CD), (2) SOD-CD mice, (3) WT
      mice on CR (WT-CR), and (4) SOD-CR. Qualitative analyses revealed two types of
      Dnmt3a immunoreactive cells: type I cells--present throughout all hippocampal
      cell layers showing moderate levels of nuclear Dnmt3a-IR, and type II cells--a
      subpopulation of hippocampal cells showing very intense nuclear Dnmt3a-IR, and
      colocalization with Bromodeoxyuridine. Quantitative analyses indicated that the
      age-related increase in Dnmt3a-IR within the CA3 and CA1-2 in type I cells was
      attenuated by CR, but not by SOD overexpression. In contrast, the density of type
      II Dnmt3a immunoreactive cells showed an age-related reduction, without
      significant effects of both CR and SOD. These changes in Dnmt3a levels in the
      mouse hippocampus may have a significant impact on gene expression and associated
      cognitive functioning.

PMID- 21172420
TI  - Effect of in vitro exposure to benzo[a]pyrene, a component of cigarette smoke, on
      folliculogenesis, steroidogenesis and oocyte nuclear maturation.
AB  - We previoulsy quantified the concentration of benzo[a]pyrene (B[a]P) in the
      follicular fluid of women exposed to mainstream and/or sidestream cigarette
      smoke. The objective of this study was to quantify the effects of B[a]P-exposure,
      at concentrations representative of follicluar fluid concentrations, on
      folliculogenesis, on gonadal steroid and anti-mullerian hormone (AMH) output,
      oocyte growth, and nuclear maturation. Follicles (100-130 MUm) isolated from
      ovaries of F1 hybrid (C57BL/6j*CBA/Ca) mice were cultured for 13 days in
      increasing concentrations of B[a]P (0 ng/ml (control) to 45 ng/ml). B[a]P
      treatment inhibited (p < 0 .05) antral follicle development, decreased estradiol
      output and follicle survival at the 45.0 ng/ml dose. B[a]P exposure decreased AMH
      output overall during preantral (p = 0.014) and antral (p = 0.026) follicle
      development but had no effect on progesterone output or oocyte growth and nuclear
      maturation in surviving follicles. These data suggest that B[a]P is an important
      toxic component of cigarette smoke that adversely affects follicular development
      and survival.

PMID- 21172421
TI  - Antagonistic effects of gestational dietary exposure to low-dose vinclozolin and
      genistein on rat fetal germ cell development.
AB  - Continuous, low-dose exposure to a phytoestrogen (1 mg/kg/day genistein) and/or
      to an antiandrogenic food contaminant (1 mg/kg/day vinclozolin) has been recently
      reported to affect male reproductive tract and fertility [1] in adults. We
      investigated whether alterations of the testis are already present at the end of
      in utero exposure using the same rat model and doses following exposure from
      conception to delivery. After vinclozolin exposure, we observed in the neonate a
      slight but significant alteration of steroidogenesis and gametogenesis with a
      reduction of testosterone secretion and of the number of gonocytes. In contrast,
      genistein exposure had no effect. While the vinclozolin-genistein mixture acts in
      a synergistic manner to induce the most significant alterations in the adult,
      interestingly, genistein antagonized the deleterious effect of vinclozolin on
      germ cells in the neonate. This difference emphasizes the importance of studying
      the effects of endocrine disruptors during various developmental stages to
      understand their effects.

PMID- 21172422
TI  - Different sub-cellular localization of alpha-synuclein in the C57BL?6J mouse's
      central nervous system by two novel monoclonal antibodies.
AB  - Alpha-synuclein is a 140 amino acids' protein, widely expressed in the nervous
      system of different vertebrates and closely related with several
      neurodegenerative disorders. Although its pathological involvement is reported
      from long time, its physiological function and its role in neurodegeneration is
      not yet clear. Disposing of two new monoclonal antibodies, able to detect alpha
      synuclein in different compartments of the neurons, the aim of this study is to
      create an anatomical map of the protein's distribution in the central nervous
      system of C57 BL?6J mouse, the mouse strain most sensitive to 1-methyl 4-phenyl
      1,2,3,6-tetrahydro pyridine neurotoxicity and widely used to apply toxic models
      of Parkinson disease. The two monoclonal antibodies confirm their ability in
      visualizing the protein in distinct compartments of the neurons, since 2E3
      detects alpha-synuclein in the nerve cells' fibers, whereas 3D5 preferentially in
      the neuronal nuclei. Both antibodies, instead, are able to show alpha-synuclein
      at the synaptic terminals. The protein is ubiquitary distributed in the brain, as
      well as in the spinal cord, but its sub-cellular localization differs markedly in
      the various regions of the central nervous system. Among alpha-synuclein
      immunoreactive territories, we describe a particular organization in habenular
      nuclei, dorsal hippocampus, olfactory bulbs, brain stem nuclei and cerebellar
      cortex. This preliminary immunohistochemical study, provides the first anatomical
      map of the alpha-synuclein distribution in the C57 BL?6J mouse CNS and suggests
      that alpha-synuclein is differentially localized, at sub-cellular level, in
      different types of neurons and that, therefore, it can plays a specific role for
      each neuronal subtype. Our study in healthy C57 BL/6J mice represents a starting
      point to analyze the variations in the overall distribution of alpha-synuclein in
      mouse models of Parkinson disease.

PMID- 21172424
TI  - Uncoupling protein-2 attenuates glucose-stimulated insulin secretion in INS-1E
      insulinoma cells by lowering mitochondrial reactive oxygen species.
AB  - Glucose-stimulated insulin secretion (GSIS) by pancreatic beta cells is regulated
      by mitochondrial uncoupling protein-2 (UCP2), but opposing phenotypes, GSIS
      improvement and impairment, have been reported for different Ucp2-ablated mouse
      models. By measuring mitochondrial bioenergetics in attached INS-1E insulinoma
      cells with and without UCP2, we show that UCP2 contributes to proton leak and
      attenuates glucose-induced rises in both respiratory activity and the coupling
      efficiency of oxidative phosphorylation. Strikingly, the GSIS improvement seen
      upon UCP2 knockdown in INS-1E cells is annulled completely by the cell-permeative
      antioxidant MnTMPyP. Consistent with this observation, UCP2 lowers mitochondrial
      reactive oxygen species at high glucose levels. We conclude that UCP2 plays both
      regulatory and protective roles in beta cells by acutely lowering GSIS and
      chronically preventing oxidative stress. Our findings thus provide a mechanistic
      explanation for the apparently discrepant findings in the field.

PMID- 21172423
TI  - Factors influencing protein tyrosine nitration--structure-based predictive
      models.
AB  - Models for exploring tyrosine nitration in proteins have been created based on 3D
      structural features of 20 proteins for which high-resolution X-ray
      crystallographic or NMR data are available and for which nitration of 35 total
      tyrosines has been experimentally proven under oxidative stress. Factors
      suggested in previous work to enhance nitration were examined with quantitative
      structural descriptors. The role of neighboring acidic and basic residues is
      complex: for the majority of tyrosines that are nitrated the distance to the
      heteroatom of the closest charged side chain corresponds to the distance needed
      for suspected nitrating species to form hydrogen bond bridges between the
      tyrosine and that charged amino acid. This suggests that such bridges play a very
      important role in tyrosine nitration. Nitration is generally hindered for
      tyrosines that are buried and for those tyrosines for which there is insufficient
      space for the nitro group. For in vitro nitration, closed environments with
      nearby heteroatoms or unsaturated centers that can stabilize radicals are
      somewhat favored. Four quantitative structure-based models, depending on the
      conditions of nitration, have been developed for predicting site-specific
      tyrosine nitration. The best model, relevant for both in vitro and in vivo cases,
      predicts 30 of 35 tyrosine nitrations (positive predictive value) and has a
      sensitivity of 60/71 (11 false positives).

PMID- 21172425
TI  - In vivo inhibition of l-buthionine-(S,R)-sulfoximine-induced cataracts by a novel
      antioxidant, N-acetylcysteine amide.
AB  - The effects of N-acetylcysteine amide (NACA), a free radical scavenger, on
      cataract development were evaluated in Wistar rat pups. Cataract formation was
      induced in these animals with an intraperitoneal injection of a glutathione (GSH)
      synthesis inhibitor, l-buthionine-(S,R)-sulfoximine (BSO). To assess whether NACA
      has a significant impact on BSO-induced cataracts, the rats were divided into
      four groups: (1) control, (2) BSO only, (3) NACA only, and (4) NACA+BSO. The
      control group received only saline ip injections on postpartum day 3, the BSO
      only group was given ip injections of BSO (4mmol/kg body wt), the NACA-only group
      received ip injections of only NACA (250mg/kg body wt), and the NACA+BSO group
      was given a dose of NACA 30min before administration of the BSO injection. The
      pups were sacrificed on postpartum day 15, after examination under a slit-lamp
      microscope. Their lenses were analyzed for selective oxidative stress parameters,
      including glutathione (reduced and oxidized), protein carbonyls, catalase,
      glutathione peroxidase, glutathione reductase, and malondialdehyde. The lenses of
      pups in both the control and the NACA-only groups were clear, whereas all pups
      within the BSO-only group developed well-defined cataracts. It was found that
      supplemental NACA injections during BSO treatment prevented cataract formation in
      most of the rat pups in the NACA+BSO group. Only 20% of these pups developed
      cataracts, and the rest retained clear lenses. Further, GSH levels were
      significantly decreased in the BSO-only treated group, but rats that received
      NACA injections during BSO treatment had these levels of GSH replenished. Our
      findings indicate that NACA inhibits cataract formation by limiting protein
      carbonylation, lipid peroxidation, and redox system components, as well as
      replenishing antioxidant enzymes.

PMID- 21172426
TI  - Substrate and inhibitor specificities differ between human cytosolic and
      mitochondrial thioredoxin reductases: Implications for development of specific
      inhibitors.
AB  - The cytosolic and mitochondrial thioredoxin reductases (TrxR1 and TrxR2) and
      thioredoxins (Trx1 and Trx2) are key components of the mammalian thioredoxin
      system, which is important for antioxidant defense and redox regulation of cell
      function. TrxR1 and TrxR2 are selenoproteins generally considered to have
      comparable properties, but to be functionally separated by their different
      compartments. To compare their properties we expressed recombinant human TrxR1
      and TrxR2 and determined their substrate specificities and inhibition by metal
      compounds. TrxR2 preferred its endogenous substrate Trx2 over Trx1, whereas TrxR1
      efficiently reduced both Trx1 and Trx2. TrxR2 displayed strikingly lower activity
      with dithionitrobenzoic acid (DTNB), lipoamide, and the quinone substrate juglone
      compared to TrxR1, and TrxR2 could not reduce lipoic acid. However, Sec-deficient
      two-amino-acid-truncated TrxR2 was almost as efficient as full-length TrxR2 in
      the reduction of DTNB. We found that the gold(I) compound auranofin efficiently
      inhibited both full-length TrxR1 and TrxR2 and truncated TrxR2. In contrast, some
      newly synthesized gold(I) compounds and cisplatin inhibited only full-length
      TrxR1 or TrxR2 and not truncated TrxR2. Surprisingly, one gold(I) compound,
      [Au(d2pype)(2)]Cl, was a better inhibitor of TrxR1, whereas another,
      [(iPr(2)Im)(2)Au]Cl, mainly inhibited TrxR2. These compounds also inhibited TrxR
      activity in the cytoplasm and mitochondria of cells, but their cytotoxicity was
      not always dependent on the proapoptotic proteins Bax and Bak. In conclusion,
      this study reveals significant differences between human TrxR1 and TrxR2 in
      substrate specificity and metal compound inhibition in vitro and in cells, which
      may be exploited for development of specific TrxR1- or TrxR2-targeting drugs.

PMID- 21172428
TI  - Pathogenetic role of eNOS uncoupling in cardiopulmonary disorders.
AB  - The homodimeric flavohemeprotein endothelial nitric oxide synthase (eNOS)
      oxidizes l-arginine to l-citrulline and nitric oxide (NO), which acutely
      vasodilates blood vessels and inhibits platelet aggregation. Chronically, eNOS
      has a major role in the regulation of blood pressure and prevention of
      atherosclerosis by decreasing leukocyte adhesion and smooth muscle proliferation.
      However, a disturbed vascular redox balance results in eNOS damage and uncoupling
      of oxygen activation from l-arginine conversion. Uncoupled eNOS monomerizes and
      generates reactive oxygen species (ROS) rather than NO. Indeed, eNOS uncoupling
      has been suggested as one of the main pathomechanisms in a broad range of
      cardiovascular and pulmonary disorders such as atherosclerosis, ventricular
      remodeling, and pulmonary hypertension. Therefore, modulating uncoupled eNOS, in
      particular eNOS-dependent ROS generation, is an attractive therapeutic approach
      to preventing and/or treating cardiopulmonary disorders, including protective
      effects during cardiothoracic surgery. This review provides a comprehensive
      overview of the pathogenetic role of uncoupled eNOS in both cardiovascular and
      pulmonary disorders. In addition, the related therapeutic possibilities such as
      supplementation with the eNOS substrate l-arginine, volatile NO, and direct NO
      donors as well as eNOS modulators such as the eNOS cofactor tetrahydrobiopterin
      and folic acid are discussed in detail.

PMID- 21172427
TI  - Increased mitochondrial matrix-directed superoxide production by fatty acid
      hydroperoxides in skeletal muscle mitochondria.
AB  - Previous studies have shown that muscle atrophy is associated with mitochondrial
      dysfunction and an increased rate of mitochondrial reactive oxygen species
      production. We recently demonstrated that fatty acid hydroperoxides (FA-OOHs) are
      significantly elevated in mitochondria isolated from atrophied muscles. The
      purpose of this study was to determine whether FA-OOHs can alter skeletal muscle
      mitochondrial function. We found that FA-OOHs (at low-micromolar concentrations)
      induce mitochondrial dysfunction assessed by a decrease in the rate of ATP
      production, oxygen consumption, and activity of respiratory chain complexes I and
      III. Using methods to distinguish superoxide release toward the matrix and toward
      the intermembrane space, we demonstrate that FA-OOHs significantly elevate
      oxidative stress in the mitochondrial matrix (and not the intermembrane space),
      with complex I as the major site of superoxide production (most probably from a
      site upstream of the ubiquinone binding site but downstream from the flavin
      binding site-the iron sulfur clusters). Our results are the first to indicate
      that FA-OOHs are important modulators of mitochondrial function and oxidative
      stress in skeletal muscle mitochondria and may play an important role in muscle
      atrophies that are associated with increased generation of FA-OOHs, e.g.,
      denervation-induced muscle atrophy.

PMID- 21172429
TI  - Nox2-based NADPH oxidase mediates HIV-1 Tat-induced up-regulation of VCAM-1/ICAM
      1 and subsequent monocyte adhesion in human astrocytes.
AB  - Up-regulation of adhesion molecules such as vascular cell adhesion molecule-1
      (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) by the HIV-1
      transactivator of transcription (Tat) in activated microglia and astrocytes may
      play a pivotal role during the development of AIDS-related encephalitis and
      dementia. Previous studies demonstrated that HIV-1 Tat-induced up-regulation of
      adhesion molecules was mediated by reactive oxygen species (ROS), although the
      mechanisms underlying HIV-1 Tat-induced ROS generation are unknown. In this
      study, we examined the possible role of NADPH oxidase in HIV-1 Tat-induced up
      regulation of adhesion molecules in astroglioma cell lines. HIV-1 Tat-induced up
      regulation of VCAM-1/ICAM-1 and subsequent increased adhesion of monocytes to
      astrocytes were blocked by a general NADPH oxidase inhibitor, diphenylene
      iodonium, and a specific inhibitor of NADPH oxidase assembly, 9R3A-gp91ds. Nox2
      knockdown using small interfering RNA (siRNA) inhibited HIV-1 Tat-induced up
      regulation of adhesion molecules and subsequent increased adhesion of monocytes
      to astrocytes. Nox2 siRNA blocked HIV-1 Tat-induced ROS production, increase in
      NADPH oxidase activity, and Rac1 activation. Furthermore, Nox2 siRNA decreased
      HIV-1 Tat-induced NF-kappaB activation as well as activation of MAP kinases
      including ERK, JNK, and p38. These data indicate that Nox2-based NADPH oxidase is
      responsible for HIV-1 Tat-induced generation of ROS and plays an important role
      in the up-regulation of adhesion molecules such as VCAM-1/ICAM-1 and subsequent
      increased adhesion of monocytes to astrocytes and serves as a novel target for
      HIV-1 Tat-mediated neurological diseases.

PMID- 21172430
TI  - Interaction of angio-associated migratory cell protein with the TPalpha and
      TPbeta isoforms of the human thromboxane A2 receptor.
AB  - In humans, thromboxane (TX) A2 signals through the TPalpha and TPbeta isoforms of
      its G-protein coupled TXA2 receptor (TP) to mediate a host of (patho)physiologic
      responses. Herein, angio-associated migratory cell protein (AAMP) was identified
      as a novel interacting partner of both TPalpha and TPbeta through an interaction
      dependent on common (residues 312-328) and unique (residues 366-392 of TPbeta)
      sequences within their carboxyl-terminal (C)-tail domains. While the interaction
      was constitutive in mammalian cells, agonist-stimulation of TPalpha/TPbeta led to
      a transient dissociation of AAMP from immune complexes which coincided with a
      transient redistribution of AAMP from its localization in an intracellular
      fibrous network. Although the GTPase RhoA is a downstream effector of both AAMP
      and the TPs, AAMP did not influence TP-mediated RhoA or vice versa. Small
      interfering RNA (siRNA)-mediated disruption of AAMP expression decreased
      migration of primary human coronary artery smooth muscle cells (1 degrees 
      hCoASMCs). Moreover, siRNA-disruption of AAMP significantly impaired 1 degrees 
      hCoASMC migration in the presence of the TXA2 mimetic U46619 but did not affect
      VEGF-mediated cell migration. Given their roles within the vasculature, the
      identification of a specific interaction between TPalpha/TPbeta and AAMP is
      likely to have substantial functional implications for vascular pathologies in
      which they are both implicated.

PMID- 21172431
TI  - Transcriptional control of metabolic and inflammatory pathways by nuclear
      receptor SUMOylation.
AB  - Nuclear receptors (NRs) exert crucial functions in controlling metabolism and
      inflammation by both positively and negatively regulating gene expression. Recent
      evidence suggests that the transcriptional activities of many NRs can be
      modulated and even re-directed through post-translational modification by small
      ubiquitin-related modifiers (SUMO). SUMOylation triggers a plethora of diverse
      molecular events that can alter both the fate and function of modified NRs at the
      nongenomic, genomic, and epigenomic level. However, it is the intriguing link of
      SUMOylation to transcriptional repression, and in particular to transrepression,
      that has emerged as a common underlying mechanism that impacts on biological
      processes controlled by NRs. It further appears that the cell-type-specific
      SUMOylation status of NRs can be regulated by ligands and by signal-dependent
      crosstalk of post-translational modifications. Given the causal role of altered
      NR signaling in the development and pathogenesis of human diseases, it is likely
      that aberrant SUMO conjugation, deconjugation, or interpretation contributes to
      these alterations. Here, we review the current progress made in both the study
      and understanding of the molecular mechanisms and consequences of NR SUMOylation
      and also discuss the physiological and pharmacological implications with a
      particular focus on transrepression pathways that link metabolism and
      inflammation. This article is part of a Special Issue entitled: Translating
      nuclear receptors from health to disease.

PMID- 21172432
TI  - Functional and physiological genomics of estrogen-related receptors (ERRs) in
      health and disease.
AB  - Orphan nuclear receptors, in a manner comparable to classic steroid hormone
      receptors, regulate key developmental and physiological processes. However, the
      lack of appropriate pharmacological tools has often hindered the identification
      and study of their biological functions. In this review, we demonstrate that
      functional and physiological genomics are effective alternatives to discover
      biological functions associated with orphan nuclear receptors. Indeed, we
      document that these approaches have allowed for the unambiguous identification of
      the estrogen-related receptors (ERRs) alpha, beta, and gamma (NR3B1, 2, and 3) as
      global regulators of cellular energy metabolism. We further show that although
      the three ERR isoforms control analogous gene networks, each isoform performs
      unique biological functions in a tissue-specific manner in response to a variety
      of physiological stressors. Finally, we discuss how the activity of the three ERR
      isoforms contributes to the development and progression of metabolic diseases as
      well as to the adaptation of cancer cells to their unique bioenergetic
      requirement. This article is part of a Special Issue entitled: Translating
      nuclear receptors from health to disease.

PMID- 21172433
TI  - Abnormal metabolism flexibility in response to high palmitate concentrations in
      myotubes derived from obese type 2 diabetic patients.
AB  - Insulin resistance in type 2 diabetes (T2D) is associated with intramuscular
      lipid (IMCL) accumulation. To determine whether impaired lipid oxidation is
      involved in IMCL accumulation, we measured expression of genes involved in
      mitochondrial oxidative metabolism or biogenesis, mitochondrial content and
      palmitate beta-oxidation before and after palmitate overload (600MUM for 16h), in
      myotubes derived from healthy subjects and obese T2D patients. Mitochondrial gene
      expression, content and network were not different between groups. Basal
      palmitate beta-oxidation was not affected in T2D myotubes, whereas after 16h of
      palmitate pre-treatment, T2D myotubes in contrast to control myotubes, showed an
      inability to increase palmitate beta-oxidation (p<0.05). Interestingly, acetyl
      CoA carboxylase (ACC) phosphorylation was increased with a tendency for
      statistical significance after palmitate pre-treatment in control myotubes
      (p=0.06) but not in T2D myotubes which can explain their inability to increase
      palmitate beta-oxidation after palmitate overload. To determine whether the
      activation of the AMP activated protein kinase (AMPK)-ACC pathway was able to
      decrease lipid content in T2D myotubes, cells were treated with AICAR and
      metformin. These AMPK activators had no effect on ACC and AMPK phosphorylation in
      T2D myotubes as well as on lipid content, whereas AICAR, but not metformin,
      increased AMPK phosphorylation in control myotubes. Interestingly, metformin
      treatment and mitochondrial inhibition by antimycin induced increased lipid
      content in control myotubes. We conclude that T2D myotubes display an impaired
      capacity to respond to metabolic stimuli.

PMID- 21172434
TI  - Novel extended-release formulation of lovastatin by one-step melt granulation: in
      vitro and in vivo evaluation.
AB  - The objective of this study was to apply a one-step melt granulation method to
      develop an extended-release formulation of lovastatin (LOV-ER). We prepared a
      formulation using PEG 6000 as binder agent in a laboratory scale high-shear
      mixer. In vitro dissolution studies showed that the release of the drug from the
      new formulation followed a zero-order kinetic with no differences in the release
      profile with either the pH media or the agitation rate. The pharmacokinetic of
      lovastatin and its metabolite lovastatin acid was evaluated after the
      administration of the new formulation to Beagle dogs in fasted conditions and
      after a high-fat meal, and compared to the marketed formulation Altoprev(r).
      After the administration of LOV-ER, extended plasma profiles of lovastatin and
      its active metabolite were achieved in both fasted conditions and after the high
      fat meal. Plasma levels of lovastatin and lovastatin acid were always higher when
      the LOV-ER formulation was administered with the high-fat meal. A high
      variability in plasma levels and pharmacokinetic parameters was obtained, being
      this variability higher when the formulation was administered under fasting
      conditions. Our results suggest that there is an increase in lovastatin
      bioavailability when the formulation is administered after the high-fat meal.
      When we compare LOV-ER and Altoprev(r), both administered after the high-fat
      meal, we found significant differences (p<0.05) in C(max) of lovastatin and in
      AUC(0-infinity) and MRT of lovastatin acid. No differences were detected between
      both formulations in fasting conditions. In this regard, the high-fat meal seems
      to increase the absorption extent of lovastatin from LOV-ER formulation and to
      delay the absorption rate of the drug from Altoprev(r). In conclusion, we
      developed a lovastatin formulation that provided extended plasma levels that
      confirm that one-step melt granulation in high-shear mixer could be an easy and
      cost-effective technique for extended-release formulation development.

PMID- 21172435
TI  - Surfactant protein A (SP-A)-tacrolimus complexes have a greater anti-inflammatory
      effect than either SP-A or tacrolimus alone on human macrophage-like U937 cells.
AB  - Intratracheal administration of immunosuppressive agents to the lung is a novel
      treatment after lung transplantation. Nanoparticles of tacrolimus (FK506) might
      interact with human SP-A, which is the most abundant lipoprotein in the alveolar
      fluid. This study was undertaken to determine whether the formation of FK506/SP-A
      complexes interferes with FK506 immunosuppressive actions on stimulated human
      macrophage-like U937 cells. We found that SP-A was avidly bound to FK506 (K(d) =
      35 +/- 4nM), as determined by solid phase-binding assays and dynamic light
      scattering. Free FK506, at concentrations <= 1 MUM, had no effect on the
      inflammatory response of LPS-stimulated U937 macrophages. However, coincubation
      of FK506 and SP-A, at concentrations where each component alone did not affect
      LPS-stimulated macrophage response, significantly inhibited LPS-induced NF-kappaB
      activation and TNF-alpha secretion. Free FK506, but not FK506/SP-A, functioned as
      substrate for the efflux transporter P-glycoprotein. FK506 bound to SP-A was
      delivered to macrophages by endocytosis, since several endocytosis inhibitors
      blocked FK506/SP-A anti-inflammatory effects. This process depended partly on SP
      A binding to its receptor, SP-R210. These results indicate that FK506/SP-A
      complexes have a greater anti-inflammatory effect than either FK506 or SP-A alone
      and suggest that SP-A strengthened FK506 anti-inflammatory activity by
      facilitating FK506 entrance into the cell, overcoming P-glycoprotein.

PMID- 21172436
TI  - Modelling of molecular phase transitions in pharmaceutical inhalation compounds:
      an in silico approach.
AB  - Molecular dynamic simulations have been successfully utilised with molecular
      modelling to estimate the glass transition temperature (T(g)) of polymers. In
      this paper, we use a similar approach to predict the T(g) of a small
      pharmaceutical molecule, beclomethasone dipropionate (BDP). Amorphous
      beclomethasone dipropionate was prepared by spray-drying. The amorphous nature of
      the spray-dried material was confirmed with scanning electron microscopy,
      differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD).
      Molecular models for amorphous BDP were constructed using the amorphous cell
      module in Discovery studioTM. These models were used in a series of molecular
      dynamic simulations to predict the glass transition temperature. The T(g) of BDP
      was determined by isothermal-isobaric molecular dynamic simulations, and
      different thermodynamic parameters were obtained in the temperature range of -150
      to 400 degrees C. The discontinuity at a specific temperature in the plot of
      temperature versus amorphous cell volume (V) and density (rho) was considered to
      be the simulated T(g.) The predicted T(g) from four different simulation runs was
      63.8 degrees C +/- 2.7 degrees C. The thermal properties of amorphous BDP were
      experimentally determined by DSC and the experimental T(g) was found to be ~ 65
      degrees C, in good agreement with computational simulations.

PMID- 21172437
TI  - Association of ranibizumab (Lucentis(r)) or bevacizumab (Avastin(r)) with
      dexamethasone and triamcinolone acetonide: an in vitro stability assessment.
AB  - The in vitro stability of monoclonal antibodies used for age-related macular
      degeneration, ranibizumab and bevacizumab, was investigated. The aggregation
      profile of the antibodies was compared, alone and after association with
      dexamethasone sodium phosphate or triamcinolone acetonide. Commercial
      formulations of ranibizumab and bevacizumab were dialysed into three different
      buffers. After dialysis, samples were stored at 4 degrees C, 25 degrees C and 40
      degrees C during 35 days, alone and in combination with dexamethasone sodium
      phosphate, triamcinolone acetonide phosphate solution or triamcinolone acetonide
      suspension. Combined formulations based on both commercial formulations were
      investigated as well. The aggregation state of the antibodies was measured by
      multi-angle light scattering (MALS) after separation by asymmetrical flow field
      flow fractionation (AFFF) or size-exclusion chromatography (SEC). Ranibizumab
      results to be more stable than bevacizumab, alone and in combination with
      dexamethasone sodium phosphate or triamcinolone acetonide. Elevation in
      concentration, pH and temperature causes a decrease in stability of both
      antibodies. The association of triamcinolone acetonide phosphate solution with
      either ranibizumab or bevacizumab is observed to be the least stable combination
      of all samples tested. Dexamethasone sodium phosphate was shown to have a
      stabilizing effect on bevacizumab, although this is not the case for its
      combination with the commercial formulation Avastin(r). The results demonstrate
      that the in vitro association of either ranibizumab or bevacizumab with
      dexamethasone sodium phosphate or triamcinolone acetonide suspension does not
      decrease the stability of these antibodies. Although ranibizumab is more stable
      than bevacizumab in vitro, further research has to point out how this affects
      their mechanism of action in vivo.

PMID- 21172439
TI  - High-throughput construction of expression system using yeast Pichia pastoris,
      and its application to membrane proteins.
AB  - The well-established method for high-throughput construction of an expression
      system of the yeast Saccharomyces cerevisiae uses homologous recombination
      between an expression plasmid and a target gene (with homologous regions of the
      plasmid on both ends added by PCR). This method has been widely used for membrane
      proteins using plasmids containing GFP, and has been successfully used to
      investigate the cellular localization and solubilization conditions of the
      proteins. Although the methanol-utilizing yeast Pichia pastoris is known as an
      excellent expression host, a method for high-throughput construction of an
      expression system like that in S. cerevisiae has not been reported. In this
      study, we have attempted to construct expression systems via homologous
      recombination in P. pastoris. The insertion of genes into a plasmid could be
      easily checked by colony-PCR. Expression systems for seven membrane proteins of
      medaka fish (Oryzias latipes) and yeast (S. cerevisiae) were constructed, and the
      expression of proteins was analyzed by fluorescence spectra, fluorescence
      microscopy, and SDS-PAGE (in-gel fluorescence detection).

PMID- 21172438
TI  - 17beta-Estradiol regulates oxidative stress in prostate cancer cell lines
      according to ERalpha/ERbeta ratio.
AB  - Estrogen action is mediated by the two receptor isoforms: estrogen receptor alpha
      and beta. Both receptors are expressed in human prostate tissue and have
      different action profiles. ERalpha is positively correlated with the malignancy
      of prostate cancer, while ERbeta may protect against abnormal prostate cell
      growth. 17beta-Estradiol (E2), at least in part, induces cancerous
      transformations by causing deleterious mutations through the formation of
      reactive oxygen species (ROS). The aim was to study the effect of E2 on oxidative
      stress and the expression of uncoupling proteins (UCPs) and antioxidant enzymes
      in several prostate cancer cell lines with different ERalpha/ERbeta ratios. The
      cell prostate lines with a lower ERalpha/ERbeta ratio had lower oxidative stress,
      which could be partially explained by the increased expression of antioxidant
      enzymes and UCPs. Moreover, the action of E2 on the expression of antioxidant
      enzymes and UCPs was dual and dependent on the ERalpha/ERbeta ratio. Treatments
      with 0.1 nM E2 in cell lines with high ERalpha/ERbeta ratio produced a decrease
      in antioxidant enzymes and UCPs levels, with an increase in ROS production. These
      effects disappeared when the treatment was done in the presence of an ERalpha
      antagonist (MPP). In the cell lines with greatest levels of ERbeta and the lowest
      ERalpha/ERbeta ratio, E2 treatment caused the up-regulation of antioxidant
      enzymes and UCPs with a look-up decrease in ROS production. These effects were
      reversed when the cells were treated with E2 in the presence of an ERbeta
      antagonist (R,R-THC). On the whole, our results suggest a dual E2 effect;
      increasing or decreasing oxidative stress in part by modulation of UCPs and
      antioxidant enzymes according to the abundance ERbeta and ERalpha/ERbeta ratio in
      prostate cancer cell lines.

PMID- 21172440
TI  - High-level soluble expression of recombinant human manganese superoxide dismutase
      in Escherichia coli, and its effects on proliferation of the leukemia cell.
AB  - Manganese superoxide dismutase (Mn-SOD) is one of the major enzymes responsible
      for the defense against oxidative damage due to reactive oxygen species (ROS) in
      the mitochondria. The present study aimed to produce and evaluate the genetically
      engineered manganese superoxide dismutase protein. A recombinant plasmid
      containing DNA segment coding Mn-SOD protein was transformed into Escherichia
      coli (E. coli) Rosetta-gami strain, for expression. After induction with IPTG, an
      expected molecular mass of 25 kDa was detected by SDS-PAGE. After Ni-NTA affinity
      chromatography purification, the purity rate came up to 95%. UV spectroscopy data
      for our preparations indicated that a peak at 275 nm existed in the spectrum. SOD
      activity assay showed that the activity of the rhMn-SOD was 1890.9 U/mg. The ORAC
      level of rhMn-SOD was 151492.2 uM Trolox equiv/mg. Furthermore, in vitro
      bioactivity assay indicated that the rhMn-SOD protein can inhibit the
      proliferation of the leukemia K562 cells.

PMID- 21172441
TI  - A small HSP gene of bloody clam (Tegillarca granosa) involved in the immune
      response against Vibrio parahaemolyticus and lipopolysaccharide.
AB  - Small heat shock proteins (sHSPs) associate with nuclei, cytoskeleton and
      membranes, and as molecular chaperones they bind partially denatured proteins,
      thereby preventing irreversible protein aggregation during stress. In the present
      study, the small heat shock proteins of Tegillarca granosa (Tg-sHSP) were
      identified from hemocytes by 3' and 5' rapid amplification of cDNA ends (RACE)
      PCR. The full-length cDNA consisted of 1005 bp with a 594 bp open reading frame
      encoding 197 amino acids. Sequence comparison showed that Tg-sHSP had low degree
      of homology to sHSP of other organisms, such as 47.8% similarity with sHSP from
      Zhikong scallop Chlamys farreri (AAR11780), 34.8% similarity with silkworm Bombyx
      mori (NP_001036941). A sHSP feature domain Alpha-crystallin domain (ACD) and
      V/IXI/V motif in the C-terminal extension were identified in Tg-sHSP, indicating
      that Tg-sHSP should be a new member of sHSP family. Quantitative RT-PCR assay was
      developed to detect the mRNA expression of Tg-sHSP in five different tissues.
      Higher-level mRNA expression of Tg-sHSP was detected in the tissues of hemocytes
      and mantle. The up-regulation of Tg-sHSP after bacteria Vibrio parahaemolyticus
      and lipopolysaccharide (LPS) challenge showed that sHSPs play a pivotal role in
      anti-bacterial immunity. These results together indicated that Tg-sHSP would
      provide candidate promising therapeutic or prophylactic agents in health
      management and diseases control of clam aquaculture.

PMID- 21172442
TI  - Introduction to machine learning for brain imaging.
AB  - Machine learning and pattern recognition algorithms have in the past years
      developed to become a working horse in brain imaging and the computational
      neurosciences, as they are instrumental for mining vast amounts of neural data of
      ever increasing measurement precision and detecting minuscule signals from an
      overwhelming noise floor. They provide the means to decode and characterize task
      relevant brain states and to distinguish them from non-informative brain signals.
      While undoubtedly this machinery has helped to gain novel biological insights, it
      also holds the danger of potential unintentional abuse. Ideally machine learning
      techniques should be usable for any non-expert, however, unfortunately they are
      typically not. Overfitting and other pitfalls may occur and lead to spurious and
      nonsensical interpretation. The goal of this review is therefore to provide an
      accessible and clear introduction to the strengths and also the inherent dangers
      of machine learning usage in the neurosciences.

PMID- 21172443
TI  - Multiple brain signatures of integration in the comprehension of degraded speech.
AB  - When listening to speech under adverse conditions, expectancies resulting from
      semantic context can have a strong impact on comprehension. Here we ask how
      minimal variations in semantic context (cloze probability) affect the unfolding
      comprehension of acoustically degraded speech. Three main results are observed in
      the brain electric response. First, auditory evoked responses to a degraded
      sentence's onset (N100) correlate with participants' comprehension scores, but
      are generally more vigorous for more degraded sentences. Second, a pronounced
      N400 in response to low-cloze sentence-final words, reflecting the integration
      effort of words into context, increases linearly with improving speech
      intelligibility. Conversely, transient enhancement in Gamma band power (gamma,
      ~40-70 Hz) during high-cloze sentence-final words (~600 ms) reflects top-down
      facilitated integration. This gamma-band effect also varies parametrically with
      signal quality. Third, a negative correlation of N100 amplitude at sentence onset
      and the later gamma-band response is found in moderately degraded speech. This
      reflects two partly distinct neural strategies when dealing with moderately
      degraded speech; a more "bottom-up," resource-allocating, and effortful versus a
      more "top-down," associative and facilitatory strategy. Results also emphasize
      the non-redundant contributions of phase-locked (evoked) and non-phase-locked
      (induced) oscillatory brain dynamics in auditory EEG.

PMID- 21172444
TI  - Task-specific activity and connectivity within the mentalizing network during
      emotion and intention mentalizing.
AB  - Mentalizing, i.e. the process of inferring another person's mental state, is
      thought to be primarily subserved by three brain regions, the VMPFC (ventromedial
      prefrontal cortex), precuneus and TPJ (temporo-parietal junction). However, it is
      still unclear what the exact roles of these regions in mentalizing are. Here, we
      compare activity within, and functional connectivity between, the VMPFC,
      precuneus and TPJ during two different mentalizing tasks. Specifically, we
      examine whether inferring another person's emotion ("emotion mentalizing") and
      inferring another person's intention ("intention mentalizing") activate similar
      or distinct subregions within the VMPFC, precuneus and TPJ, and whether these
      different kinds of mentalizing are associated with different patterns of
      functional connectivity between these regions. Our results indicate that emotion
      mentalizing and intention mentalizing activate partly distinct subregions of the
      right and left TPJ that can be spatially separated across participants. These
      subregions also showed different patterns of functional connectivity with the
      VMPFC: a more anterior region of the right and left TPJ, which was more strongly
      activated during emotion mentalizing, showed stronger functional connectivity
      with the VMPFC, particularly during emotion mentalizing, than a more posterior
      region that was more strongly activated during intention mentalizing. Critically,
      this double dissociation became evident only when the fine-scale distribution of
      activity within activated regions was analysed, and despite the fact that there
      was also a significant overlap of activity during the two tasks. Our findings
      provide first evidence that different neural modules might have evolved within
      the TPJ that show distinct patterns of functional connectivity and might subserve
      slightly different subfunctions of mentalizing.

PMID- 21172445
TI  - Individuals with patellofemoral pain exhibit greater patellofemoral joint stress:
      a finite element analysis study.
AB  - OBJECTIVE: To test the hypothesis that individuals with patellofemoral pain (PFP)
      exhibit greater patellofemoral joint stress profiles compared to persons who are
      pain-free. METHODS: Ten females with PFP and ten gender, age, and activity
      matched pain-free controls participated. Patella and femur stress profiles were
      quantified utilizing subject-specific finite element (FE) models of the
      patellofemoral joint at 15 degrees  and 45 degrees  of knee flexion. Input
      parameters for the FE model included: (1) joint geometry, (2) quadriceps muscle
      forces, and (3) weight-bearing patellofemoral joint kinematics. Using a nonlinear
      FE solver, quasi-static loading simulations were performed to quantify each
      subject's patellofemoral joint stress profile during a static squatting maneuver.
      The patella and femur peak and mean hydrostatic pressure as well as the peak and
      mean octahedral shear stress for the elements representing the chondro-osseous
      interface were quantified. RESULTS: Compared to the pain-free controls,
      individuals with PFP consistently exhibited greater peak and mean hydrostatic
      pressure as well as peak and mean octahedral shear stress for the elements
      representing the patella and femur chondro-osseous interface across the two knee
      flexion angles tested (15 degrees  and 45 degrees ). CONCLUSIONS: The combined
      finding of elevated hydrostatic pressure and octahedral shear stress across the
      two knee flexion angles supports the premise that PFP may be associated with
      elevated joint stress. Therefore, treatments aimed at decreasing patellofemoral
      joint stress may be indicated in this patient population.

PMID- 21172446
TI  - Histopathology grading systems for characterisation of human knee osteoarthritis-
      reproducibility, variability, reliability, correlation, and validity.
AB  - OBJECTIVE: To determine the reliability, reproducibility, variability and
      validity of the Osteoarthritis Cartilage Histopathology (OACH) assessment system
      and Mankin Histological-Histochemical Grading System (HHGS) when applied to the
      characterisation of the osteoarthritic human knee. METHOD: Osteoarthritic knees
      of 10 patients undergoing unilateral knee arthroplasty were assessed, and
      assigned Kellgren-Lawrence and Line Drawing Atlas (LDA) radiology scores. The
      tibial plateaux were scored using the Modified Collins (MC) and Societe Francaise
      d'Arthroscopie (SFA). Three observers twice scored both the OACH and HHGS across
      a single complete medial and lateral tibial plateau transect taken to include the
      region with the most severe osteoarthritis (OA) lesion. Intra- and inter-observer
      reliability, reproducibility, variability and validity were assessed, and the
      correlation between the two histopathology scoring systems was calculated.
      RESULT: Both histopathology scoring systems were determined to be reliable and
      reproducible exhibiting similar variability, when applied to characterise OA
      specimens sampled from a well defined patient group with knee OA. A strong
      correlation between the mean OACH and mean HHGS scores was identified (Spearman's
      rho 0.980, P<0.0001). CONCLUSION: Both scoring systems implemented provide useful
      measures in the characterisation of knee osteoarthritis. It is of note that an
      additional parameter within the OACH score over the HHGS defines the extent of
      the disease, where the HHGS is a grade attributed to the most representative
      level of the biological aggression within the OA lesions. This study has
      confirmed the OACH system's utility in human knee OA and is supported by a
      significant correlation with the established HHGS.

PMID- 21172447
TI  - microRNA methylation profile has prognosis impact in acute lymphoblastic leukemia
      patients undergoing stem cell transplantation.

PMID- 21172448
TI  - Reduced-intensity allografting in childhood acute lymphoblastic leukemia.

PMID- 21172449
TI  - Reduced body mass gain in small passerines during migratory stopover under
      simulated heat wave conditions.
AB  - For birds that migrate long distances, maximizing the rate of refueling at
      stopovers is advantageous, but ambient conditions may adversely influence this
      vital process. We simulated a 3-day migratory stopover for garden warblers
      (Sylvia borin) and compared body temperatures (T(b)) and rates of refueling under
      conditions of a heat wave (T(a)=40  degrees C by day, and 15  degrees C at night)
      with those under more moderate conditions (T(a)=27  degrees C by day, and 15 
      degrees C at night). We measured T(b) with implanted thermo-sensitive radio
      transmitters. Birds had significantly lower rates of body mass gain on the first
      day of stopover (repeated measures mixed model ANOVA, p=0.002) affecting body
      mass during the entire stopover (p=0.034) and higher maximum T(b) during the day
      when exposed to high T(a) than when exposed to moderate T(a) (p=0.002). In
      addition, the birds exposed to high T(a) by day had significantly lower minimum
      T(b) at night than those exposed to moderate daytime T(a) (p=0.048), even though
      T(a) at night was the same for both groups. We interpret this lower nighttime
      T(b) to be a means of saving energy to compensate for elevated daytime
      thermoregulatory requirements, while higher T(b) by day may reduce protein
      turnover. All effects on T(b) were significantly more pronounced during the first
      day of stopover than on days two and three, which may be linked to the rate of
      renewal of digestive function during stopover. Our results suggest that
      environmental factors, such as high T(a), constrain migratory body mass gain.
      Extreme high T(a) and heat waves are predicted to increase due to global climate
      change, and thus are likely to pose increasing constraints on regaining body mass
      during stopover and therefore migratory performance in migratory birds.

PMID- 21172450
TI  - Failure of mycoplasma lipoprotein MALP-2 to induce NK cell activation through
      dendritic cell TLR2.
AB  - Macrophage-activating lipopeptide 2 (MALP-2), a mycoplasmal diacylated
      lipopeptide with palmitic acid moiety (Pam2), activates Toll-like receptor (TLR)
      2 to induce inflammatory cytokines. TLR2 is known to mature myeloid dendritic
      cells (mDC) to drive mDC contact-mediated natural killer (NK) cell activation.
      Here we tested if MALP-2 activates NK cells through stimulation of TLR2 on mDC.
      Although synthetic MALP-2 with 6 or 14 amino acids (a.a.) stretch (designated as
      s and f) matured mDC to induce IL-6, IL-12p40 and TNF-alpha to a similar extent,
      they far less activated NK cells than Pam2CSK4, a positive control of 6 a.a.
      containing diacyl lipopeptide. MALP-2s and f were TLR2/6 agonists and activate
      the MyD88 pathway similar to Pam2CSK4, but MALP-2s having the CGNNDE sequence
      acted on mDC TLR2 to barely induce external NK activation. Even the s form, with
      slightly high induction of IL-6 compared to the f form, barely induced in vivo
      growth retardation of NK-sensitive implant tumor. Pam2CSK4 and MALP-2 have the
      common lipid moiety but different peptides, which are crucial for NK cell
      activation. The results infer that MALP-2 is applicable to a cytokine inducer but
      not to an adjuvant for antitumor NK immunotherapy.

PMID- 21172451
TI  - Single-walled carbon nanotube induction of rat aortic endothelial cell apoptosis:
      Reactive oxygen species are involved in the mitochondrial pathway.
AB  - The use of nano-sized materials offers exciting new options in technical and
      medical applications. Single-walled carbon nanotubes are emerging as
      technologically important in different industries. However, adverse effects on
      cells have been reported and this may limit their use. We previously found that
      200MUg/mL of single-walled carbon nanotubes induce apoptosis in rat aorta
      endothelial cells. The current study aimed to determine the signaling pathway
      involved in this process. We found that reactive oxygen species generation was
      involved in activation of the mitochondria-dependent apoptotic pathway. The
      finding of apoptosis was supported by a number of morphological and biochemical
      hallmarks, including chromatin condensation, internucleosomal DNA fragmentation,
      and caspase-3 activation. In conclusion, our results demonstrate that single
      walled carbon nanotubes induce apoptosis in rat aorta endothelial cells and that
      reactive oxygen species are involved in the mitochondrial pathway.

PMID- 21172452
TI  - The metabolic cascade leading to eicosanoid precursors--desaturases, elongases,
      and phospholipases A2--is altered in Zucker fatty rats.
AB  - Metabolic syndrome characterized by insulin resistance and obesity is accompanied
      by severe lipid metabolism perturbations and chronic low-grade inflammation.
      However, many unresolved questions remained regarding the regulation that
      underlie dyslipidemia, particularly the regulation of the metabolic cascade
      (synthesis and release) leading to eicosanoid precursors release. This study was
      undertaken to investigate the regulation of desaturases/elongases and
      phospholipases A(2) during the establishment of metabolic syndrome. Our results
      showed that delta-6 desaturase as well as elongase-6 expressions were upregulated
      in 3-month-old Zucker fatty rats as compared to lean littermates, independently
      of SREBP-1c activation. We also demonstrated for the first time an increase of
      liver group VII phospholipase A(2) gene expression in the obese animals together
      with a strong specific inhibition of type IVA and VIA phospholipases A(2). These
      results suggest that the regulation of unsaturated fatty acids biosynthesis and
      signalling cascade could contribute to the development of liver lipid
      dysregulation related to metabolic syndrome and may be considered as new
      potential targets in such pathological conditions.

PMID- 21172453
TI  - The lampricide 3-trifluoromethyl-4-nitrophenol (TFM) uncouples mitochondrial
      oxidative phosphorylation in both sea lamprey (Petromyzon marinus) and TFM
      tolerant rainbow trout (Oncorhynchus mykiss).
AB  - The toxicity of 3-trifluoromethyl-4-nitrophenol (TFM) appears to be due to a
      mismatch between ATP supply and demand in lamprey, depleting glycogen stores and
      starving the nervous system of ATP. The cause of this TFM-induced ATP deficit is
      unclear. One possibility is that TFM uncouples mitochondrial oxidative
      phosphorylation, thus impairing ATP production. To test this hypothesis,
      mitochondria were isolated from the livers of sea lamprey and rainbow trout, and
      O(2) consumption rates were measured in the presence of TFM or 2,4-dinitrophenol
      (2,4-DNP), a known uncoupler of oxidative phosphorylation. TFM and 2,4-DNP
      markedly increased State IV respiration in a dose-dependent fashion, but had no
      effect on State III respiration, which is consistent with uncoupling of oxidative
      phosphorylation. To determine how TFM uncoupled oxidative phosphorylation, the
      mitochondrial transmembrane potential (TMP) was recorded using the mitochondria
      specific dye rhodamine 123. Mitochondrial TMP decreased by 22% in sea lamprey,
      and by 28% in trout following treatment with 50MUmolL(-1) TFM. These findings
      suggest that TFM acted as a protonophore, dissipating the proton motive force
      needed to drive ATP synthesis. We conclude that the mode of TFM toxicity in sea
      lamprey and rainbow trout is via uncoupling of oxidative phosphorylation, leading
      to impaired ATP production.

PMID- 21172454
TI  - Quantification of serum levels of pepsinogens and gastrin to assess eradication
      of Helicobacter pylori.
AB  - BACKGROUND & AIMS: We investigated whether serum levels of pepsinogen (sPG)I and
      sPGII, the ratio of sPGI to sPGII, or serum levels of gastrin-17 (sG17), can be
      used to assess eradication of Helicobacter Pylori 8 weeks after treatment.
      METHODS: We performed a prospective study of 228 consecutive patients with H
      pylori infections. At the start of the trial (baseline), patients were assessed
      using the (13)C-urea breath test ((13)C-UBT) and endoscopy, and serum levels of
      pepsinogens and gastrin levels were measured. Patients were offered a 7-day
      triple therapy and asked to return 8 weeks after treatment for another (13)C-UBT
      and measurements of serum levels of sG17, sPGI, and sPGII (175 patients completed
      the study). RESULTS: The eradication rate of H pylori was 67%. Percentage
      variation in levels of sPGI and sPGII, the ratio of sPGI to sPGII, and in levels
      of sG17 resulted in area under the curve values of 0.858, 0.973, 0.940, and
      0.810, respectively, for H pylori eradication. A decrease of 22.7% or greater in
      the level of sPGII detected H pylori eradication with 100% sensitivity and 96.6%
      specificity. Spectrum analysis did not identify differences in accuracy.
      CONCLUSIONS: Percentage variation of sPGII levels 8 weeks after therapy for H
      pylori infection correlates with eradication. Additional studies are needed to
      confirm these results.

PMID- 21172455
TI  - Healing occurs in most patients that receive endoscopic stents for anastomotic
      leakage; dislocation remains a problem.
AB  - BACKGROUND & AIMS: There is controversy about the best way to treat esophageal
      anastomotic leakage. We evaluated the effects of treatment with self-expanding
      metal stents in patients with esophageal anastomotic leakage after esophagectomy
      or gastrectomy for cancer. METHODS: We investigated outcomes and procedure
      related complications of 115 patients who received endoscopic stents for
      anastomotic leakage after esophagectomy or gastrectomy at a university hospital
      from 2004 to 2009. We also performed a systematic literature review on stent
      therapy and compared outcomes with that of other treatment regimens for
      esophageal anastomotic leakage. RESULTS: Among the 115 patients who received
      stents, the in-hospital mortality rate was 9% and complete anastomotic healing
      was achieved in 70% (95% confidence interval [CI], 64%-76%). Stent dislocation
      occurred in 53% of the patients (95% CI, 43%-62%), in all patients with
      esophagocolonostomy, in 61% with esophagojejunostomy, and in 49% with
      esophagogastrostomy. Three percent of patients (95% CI, 1%-5%) needed laparotomy
      to remove dislocated stents. Elective endoscopic stent removal was performed in
      80% of the patients after a median of 54 days (range 17-427 d); 12% of these
      patients developed symptomatic anastomotic strictures after stent removal.
      CONCLUSIONS: Anastomoses completely heal in 70% of patients that receive
      endoscopic stents for anastomotic leakage after esophagectomy or gastrectomy.
      Stent therapy should be used in the management of patients with adequately
      perfused esophageal anastomotic leakage. However, stent dislocation remains a
      common problem after surgery.

PMID- 21172457
TI  - Gene expression profile of Ci-VSP in juveniles and adult blood cells of ascidian.
AB  - VSP is a transmembrane protein whose cytoplasmic region shows significant
      similarity to phosphatase and tensin homolog deleted on chromosome 10 (PTEN).
      Notably, VSP exhibits a unique ability to transduce electrical signals into
      phosphoinositide turnover by coupling a transmembrane voltage sensor domain to
      the PTEN-like phosphoinositide phosphatase domain. Moreover, VSP gene is known to
      be widely conserved among deuterostome genomes, though the function of VSP in
      vivo remains largely unknown. In the present study, the expression pattern of
      ascidian VSP(Ci-VSP) was examined in embryos and juveniles of a marine
      invertebrate chordate, Ciona intestinalis. RT-PCR showed that Ci-VSP is expressed
      at the larval stage and that expression persists in juveniles. Whole mount in
      situ hybridization showed that Ci-VSP is expressed in cells of the stomach,
      intestine and blood cells of 2- to 3-week-old juveniles. Moreover, double
      staining blood cells from 2-month-old adults with Ci-VSP and Ci-PTEN probes
      showed that Ci-VSP-positive cells are a distinct population, separate from cells
      expressing Ci-PTEN. These findings suggest that in addition to its previously
      suggested roles in testis or sperm, Ci-VSP plays a key role in voltage-induced
      signal transduction in cells of the digestive system and blood.

PMID- 21172456
TI  - XLMR candidate mouse gene, Zcchc12 (Sizn1) is a novel marker of Cajal-Retzius
      cells.
AB  - Sizn1 (Zcchc12) is a transcriptional co-activator that positively modulates bone
      morphogenic protein (BMP) signaling through its interaction with Smad family
      members and CBP. We have demonstrated a role for Sizn1 in basal forebrain
      cholinergic neuron specific gene expression. Furthermore, mutations in SIZN1 have
      been associated with X-linked mental retardation. Given the defined role of SIZN1
      in mental retardation, knowing its complete forebrain expression pattern is
      essential to further elucidating its role in cognition. To better define the
      dynamic expression pattern of Sizn1 during forebrain development, we investigated
      its expression in mouse brain development from embryonic day 8.0 (E8.0) to adult.
      We found that Sizn1 is primarily restricted to the ventral forebrain including
      the medial ganglionic eminence, the septum, amygdala, and striatum. In addition,
      Sizn1 expression is detected in the cortical hem and pallial-subpallial boundary
      (PSB; anti-hem); both sources of Cajal-Retzius cells. Sizn1 expression in the
      dorsal forebrain is restricted to a subset of cells in the marginal zone that
      also express Reln, indicative of Cajal-Retzius cells. These data provide novel
      information on brain regions and cell types that express Sizn1, facilitating
      further investigations into the function of Sizn1 in both development and the
      pathogenesis of mental retardation.

PMID- 21172459
TI  - A single multiplex PCR and SNaPshot minisequencing reaction of 42 SNPs to
      classify admixture populations into mitochondrial DNA haplogroups.
AB  - SNaPshot minisequencing reaction is in increasing use because of its fast
      detection of many polymorphisms in a single assay. In this work we described a
      highly sensitive single nucleotide polymorphisms (SNPs) typing method with
      detection of 42 mitochondrial DNA (mtDNA) SNPs in a single PCR and SNaPshot
      multiplex reaction, in order to allow haplogroup classification in Latin American
      admixture population. We validated the panel typing 160 Brazilian individuals.
      Complete SNP profiles were obtained from 10 pg of total DNA. We conclude that it
      is possible to build and genotype more than forty mtDNA SNPs in a single
      multiplex PCR and SNaPshot reaction, with sensitivity and reliability, resolving
      haplogroup classification in admixture populations.

PMID- 21172458
TI  - Cross-species spread of SCCmec IV subtypes in staphylococci.
AB  - Staphylococcal chromosomal cassette mec (SCCmec) is a mobile genetic element that
      carries resistance genes for beta-lactam antibiotics. Coagulase-negative
      staphylococci, such as S. epidermidis, are thought to be a reservoir of diverse
      SCCmec elements that can spread to the most virulent staphylococcal species, S.
      aureus, but very little is known about the extent of cross-species spread of
      these elements in natural populations or their dynamics in different species. We
      addressed these questions using a sample of 86 S. aureus and S. epidermidis
      isolates with SCCmec type IV that were collected from a single hospital over a
      period of 6 months. To subtype SCCmec IV, we used multiplex PCR to detect
      structural variations and we used sequences from a fragment of the ccrB gene and
      from the dru repeats to detect additional variations. Multiplex PCR had
      significantly lower typeability than ccrB:dru sequencing, due to more nontypeable
      isolates among S. epidermidis. No statistically significant differences in
      diversity were detected by subtyping method or species. Interestingly, while only
      4 of 24 subtypes (17%) were shared between species, these so-called shared
      subtypes represented 58 of 86 isolates (67%). The shared subtypes differed
      significantly between species in their frequencies. The shared subtypes were also
      significantly more concordant with genetic backgrounds in S. aureus than in S.
      epidermidis. Moreover, the shared subtypes had significantly higher minimum
      inhibitory concentrations to oxacillin in S. aureus than in S. epidermidis. This
      study has identified particular SCCmec IV subtypes with an important role in
      spreading beta-lactam resistance between species, and has further revealed some
      species differences in their abundance, linkage to genetic background, and
      antibiotic resistance level.

PMID- 21172460
TI  - Genetic and immunological processes in the pathomechanism of gluten-sensitive
      enteropathy and associated metabolic bone disorders.
AB  - Celiac disease, or gluten sensitive enteropathy is a relatively common disease of
      the jejunum, leading to malabsorption. It is an immune mediated disease, induced
      by gluten on the grounds of a specific genetic makeup. After gluten exposition
      immune processes are induced mainly by T-cells, causing typical intestinal and
      extra intestinal manifestations. The diagnosis of celiac disease is based on
      jejunal biopsy histology and the presence of antibodies against endomysium and
      tissue transglutaminase. Genetically, celiac disease is associated with HLA
      DQ2/DQ8. Strict gluten-free diet improves the clinical, histological and
      serological picture and remission may be achieved. In the etiopathogenesis of
      celiac disease several genetic and immunological mechanisms have been recognized
      in the recent years. Concerning accompanying diseases/extraintestinal
      manifestations, several disorders have been shown, including rheumatological
      diseases. In celiac disease, bone metabolic changes are more frequent compared to
      the prevalence of inflammatory join disorders. In this review, we aim to give an
      overview on various aspects of the genetic and immunological processes in the
      pathomechanism of gluten-sensitive enteropathy and associated metabolic bone
      disorders.

PMID- 21172461
TI  - 5.78 Mb terminal deletion of chromosome 15q in a girl, evaluation of NR2F2 as
      candidate gene for congenital heart defects.
AB  - All patients with terminal deletion of chromosome 15q have been reported to show
      intrauterine growth retardation, postnatal growth retardation, abnormal facial
      appearance and developmental delay. Haploinsufficiency of IGF1R was considered to
      be responsible for these symptoms. However, it is difficult to explain other
      symptoms seen in some of the patients, such as congenital heart defects by the
      absence of IGF1R alone. Here, we reported a patient with congenital heart defects
      and a 5.78 Mb terminal deletion of chromosome 15q detected by array-CGH. Among
      the patients reported to share congenital heart defects and terminal deletion of
      chromosome 15q, our patient had the smallest deletion. Evaluating the deletion
      map, NR2F2 was considered a candidate gene contributing to congenital heart
      defects in patients with terminal deletion of chromosome 15q.

PMID- 21172463
TI  - Seed proteomics.
AB  - Seeds comprise a protective covering, a small embryonic plant, and a nutrient
      storage organ. Seeds are protein-rich, and have been the subject of many mass
      spectrometry-based analyses. Seed storage proteins (SSP), which are transient
      depots for reduced nitrogen, have been studied for decades by cell biologists,
      and many of the complicated aspects of their processing, assembly, and
      compartmentation are now well understood. Unfortunately, the abundance and
      complexity of the SSP requires that they be avoided or removed prior to gel-based
      analysis of non-SSP. While much of the extant data from MS-based proteomic
      analysis of seeds is descriptive, it has nevertheless provided a preliminary
      metabolic picture explaining much of their biology. Contemporary studies are
      moving more toward analysis of protein interactions and posttranslational
      modifications, and functions of metabolic networks. Many aspects of the biology
      of seeds make then an attractive platform for heterologous protein expression.
      Herein we present a broad review of the results from the proteomic studies of
      seeds, and speculate on a potential future research directions.

PMID- 21172462
TI  - SNP-array based whole genome homozygosity mapping: a quick and powerful tool to
      achieve an accurate diagnosis in LGMD2 patients.
AB  - A large number of novel disease genes have been identified by homozygosity
      mapping and the positional candidate approach. In this study we used single
      nucleotide polymorphism (SNP) array-based, whole genome homozygosity mapping as
      the first step to a molecular diagnosis in the highly heterogeneous muscle
      disease, limb girdle muscular dystrophy (LGMD). In a consanguineous family, both
      affected siblings showed homozygous blocks on chromosome 15 corresponding to the
      LGMD2A locus. Direct sequencing of CAPN3, encoding calpain-3, identified a
      homozygous deletion c.483delG (p.Ile162SerfsX17). In a sporadic LGMD patient
      complete absence of caveolin-3 on Western blot was observed. However, a mutation
      in CAV3 could not be detected. Homozygosity mapping revealed a large homozygous
      block at the LGMD2I locus, and direct sequencing of FKRP encoding fukutin-related
      protein detected the common homozygous c.826 C>A (p.Leu276Ile) mutation.
      Subsequent re-examination of this patient's muscle biopsy showed aberrant alpha
      dystroglycan glycosylation. In summary, we show that whole-genome homozygosity
      mapping using low cost SNP arrays provides a fast and non-invasive method to
      identify disease-causing mutations in sporadic patients or sibs from
      consanguineous families in LGMD2. Furthermore, this is the first study describing
      that in addition to PTRF, encoding polymerase I and transcript release factor,
      FKRP mutations may cause secondary caveolin-3 deficiency.

PMID- 21172464
TI  - Quantitative proteomic analysis of the chemolithoautotrophic bacterium
      Nitrosomonas europaea: comparison of growing- and energy-starved cells.
AB  - Obligately aerobic ammonia-oxidizing bacteria (AOB) like Nitrosomonas europaea
      play a pivotal role in the global nitrogen cycle. Although starvation tolerance
      is a key environmental adaptation, little is known about this response in AOB.
      The goal of these studies was to compare the composition of the N. europaea
      proteome in growing- and energy-starved cells using 15N labeling and HPLC-ESI
      MS/MS. More than 6500 peptides were sequenced with high confidence, and matched
      to 876 proteins (34% of the protein coding genes). Of these, 126 proteins had two
      or more peptide forms identified by 10 or more scans, and were used in
      quantitative analysis and 27 were found to be significantly different in
      abundance between growing and starved cells. Proteins showing greater abundance
      in growing cells are geared toward biosynthesis, particularly DNA replication.
      Energy-starved cells were shifted away from biosynthesis and toward survival
      functions that included: cell envelope modification, protein
      protection/degradation, detoxification, and implementation of alternative energy
      generation mechanisms. Most of these activities have not previously been reported
      as associated with energy-starvation stress in N. europaea. This study provides
      insights into the potential effects of fluctuating environmental conditions on
      the regulation of physiological networks in N. europaea.

PMID- 21172465
TI  - Spatio-temporal structure of cell distribution in cortical bone multicellular
      units: a mathematical model.
AB  - Bone remodelling maintains the functionality of skeletal tissue by locally
      coordinating bone-resorbing cells (osteoclasts) and bone-forming cells
      (osteoblasts) in the form of Bone Multicellular Units (BMUs). Understanding the
      emergence of such structured units out of the complex network of biochemical
      interactions between bone cells is essential to extend our fundamental knowledge
      of normal bone physiology and its disorders. To this end, we propose a spatio
      temporal continuum model that integrates some of the most important interaction
      pathways currently known to exist between cells of the osteoblastic and
      osteoclastic lineage. This mathematical model allows us to test the significance
      and completeness of these pathways based on their ability to reproduce the spatio
      temporal dynamics of individual BMUs. We show that under suitable conditions, the
      experimentally observed structured cell distribution of cortical BMUs is
      retrieved. The proposed model admits travelling-wave-like solutions for the cell
      densities with tightly organised profiles, corresponding to the progression of a
      single remodelling BMU. The shapes of these spatial profiles within the
      travelling structure can be linked to the intrinsic parameters of the model such
      as differentiation and apoptosis rates for bone cells. In addition to the cell
      distribution, the spatial distribution of regulatory factors can also be
      calculated. This provides new insights on how different regulatory factors exert
      their action on bone cells leading to cellular spatial and temporal segregation,
      and functional coordination.

PMID- 21172467
TI  - Infant myocardial recovery with device and surgical repair.
AB  - A 4-month-old female infant (weight, 6.17 kg; height, 65 cm) presenting with
      tachypnea and tachycardia, and a left ventricular ejection fraction of 10%,
      deteriorated on increasing inotropic therapy and mechanical ventilation.
      Implantation of a centrifugal left ventricular assist device and institution of
      maximal medical heart failure therapy led to reverse remodeling and
      discontinuation of device support after 9 days. One week later, after failure to
      wean from the ventilator and persistence of a severely dyskinetic septum, a
      ventricular septal aneurysmectomy was done. The patient was extubated 5 days
      later followed by hospital discharge 11 days post-septal aneurysmectomy. The
      patient has done well since then with the most recent echocardiogram showing a
      65% ejection fraction.

PMID- 21172466
TI  - Identification of secretory odontoblasts using DMP1-GFP transgenic mice.
AB  - Terminal differentiation of odontoblasts from dental papilla is a long process
      involving several intermediate steps and changes in the transcriptional profile
      and expression of proteins secreted by cells in the odontoblast lineage.
      Transgenic mouse lines in which GFP expression is under the control of tissue-
      and stage specific promoters have provided powerful experimental tools for
      identification and isolation of cells at specific stages of differentiation along
      a lineage. Our previous studies showed utilization of pOBCol3.6GFP and
      pOBCol2.3GFP animals for identification of odontoblasts at early and late stages
      of polarization respectively. In the present study we used the DMP1-GFP
      transgenic animal as an experimental model to examine its expression during the
      differentiation of odontoblasts from progenitor cells in vivo and in vitro. Our
      observations showed that DMP1-GFP transgene is first activated in
      secretory/functional odontoblasts engaged in secretion of predentin and then
      transiently expressed at high levels in newly differentiated odontoblasts.
      Expression of DMP1-GFP was down-regulated in highly differentiated odontoblasts.
      The temporal and spatial pattern of expression of DMP1-GFP transgene closely
      mimics the expression of endogenous DMP1. This transgenic animal will facilitate
      studies of gene expression and biological functions in secretory/functional
      odontoblasts.

PMID- 21172468
TI  - Gastropericardial fistula-induced pyopneumopericardium after esophagectomy with
      esophagogastrectomy.
AB  - Gastropericardial fistula is an acquired disorder presenting as an abnormal
      communication between the stomach and the pericardium, with a rare incidence and
      extremely high mortality rate. We recently experienced a case of life-threatening
      gastropericardial fistula occurring as an unusual complication after an
      esophagectomy with an esophagogastrostomy for esophageal cancer treatment. A 68
      year-old man with a history of esophagectomy and esophagogastrostomy using the
      gastric pedicle for the esophageal cancer 13 years ago, visited the hospital with
      a complaint of dyspnea for 3 days. Chest roentgenogram, computed tomographic
      scan, and endoscopy showed a pneumopericardium and huge ulcer with central
      perforation in the posterior wall of the gastric pedicle.

PMID- 21172469
TI  - Single-stage hybrid repair of a mycotic lusorian artery aneurysm.

PMID- 21172470
TI  - Schwannoma of the cervical vagus nerve.

PMID- 21172471
TI  - Repair of tracheomalacia with inflammatory defect and mediastinitis.
AB  - We describe a novel repair of an anterior inflammatory tracheal defect with
      mediastinitis, which occurred after external tracheal suspension of localized
      intrathoracic tracheomalacia. The malacic tracheal segment of 4-cm length
      containing the inflammatory tracheal defect was noncircumferentially resected. A
      temporary endotracheal silicone stent was introduced, and the trachea was closed
      by a pedicled pectoralis muscle flap reinforced with an embedded rib segment.
      Retrieval of the stent 5 months postoperatively resulted in a re-epithelialized,
      persistently stable, noncollapsible tracheal segment that showed the same
      diameter and configuration as the nonreconstructed part of the trachea.

PMID- 21172472
TI  - Surgical repair of rupture of the membranous septum after blunt chest trauma.
AB  - Rupture of the membranous septum is a very rare complication of blunt chest
      trauma. In this report, we describe a 22-year-old man who sustained multiple
      blunt trauma injuries during a motor vehicle accident. Rupture of the membranous
      septum was diagnosed 48 hours after the initial trauma and the defect was closed
      with Gore-Tex (W.L. Gore & Assoc, Flagstaff, AZ). However, the operation was
      complicated by complete atrioventricular block requiring implantation of a
      permanent DDD pacemaker.

PMID- 21172473
TI  - Aortic valve replacement after transapical valve-in-valve implantation.
AB  - Transapical valve-in-valve aortic valve replacement has emerged as an attractive
      alternative for high-risk surgery in elderly patients with degenerated aortic
      bioprothesis. Despite recent encouraging results, further clinical investigation
      is required to avoid potential cases of prosthesis-aortic annulus mismatch. We
      report a surgical valve replacement in a high-risk patient with dysfunctional
      transapical, implanted aortic valve-in-valve prosthesis 1 year after
      implantation.

PMID- 21172474
TI  - Severe bronchomalacia treated by combination of Nuss procedure and aortopexy: an
      unusual therapy combination.
AB  - Aortopexy is the treatment of choice for clinically significant
      tracheobronchomalacia from external vascular compression. When a marked chest
      depression is present, aortopexy may be less effective. We report 2 patients with
      pectus excavatum and vascular compression of the trachea who, despite their young
      age, benefited from combined Nuss bar insertion and aortopexy.

PMID- 21172475
TI  - Impact of off-pump coronary artery bypass graft surgery on postoperative
      pulmonary complications in patients with chronic lung disease.
AB  - BACKGROUND: Off-pump coronary artery bypass graft surgery (OPCAB) has proven to
      be beneficial in many high-risk subgroups. This study aims to determine whether
      OPCAB lowers the incidence of pulmonary complications among patients with chronic
      lung disease (CLD) when compared with on-pump coronary artery bypass graft
      surgery (ONCAB). METHODS: From 2002 to 2007, 7,060 patients underwent isolated
      coronary artery bypass graft surgery in an academic center. Patients were
      classified according to surgery type (ONCAB or OPCAB) and presence or absence of
      CLD. A propensity score was produced to estimate each patient's likelihood of
      being assigned to OPCAB on the basis of 39 preoperative risk factors. Multiple
      logistic regression models and adjusted odds ratios with 95% confidence intervals
      were used to evaluate the effect of surgery type, CLD, and their interaction on
      pulmonary-related complications and mortality. RESULTS: Among OPCAB patients,
      15.3% (720 of 4,693) had CLD compared with 11.2% (264 of 2,367) for ONCAB. Off
      pump coronary artery bypass graft surgery was performed in 73.2% of CLD patients
      compared with 66.5% in those without CLD (p<0.0001). Chronic lung disease was
      associated with a greater incidence of prolonged ventilation, reintubation,
      pneumonia, intensive care unit hours, and non-home discharge. After propensity
      score adjustment, OPCAB was associated with a significantly reduced incidence of
      prolonged ventilation, pneumonia, intensive care unit stay, and mortality. No
      significant interactions existed between surgery type and CLD status, suggesting
      that OPCAB was equally beneficial to patients with and without CLD. CONCLUSIONS:
      In this series, patients with CLD were more likely to undergo OPCAB. Patients
      with CLD are at significantly greater risk of pulmonary-related complications
      than patients without CLD. Off-pump coronary artery bypass graft surgery reduced
      the incidence of pulmonary complications and mortality in all patients.
      Importantly, this benefit was seen similarly for patients with and without CLD.

PMID- 21172476
TI  - Invited commentary.

PMID- 21172477
TI  - Minimized cardiopulmonary bypass reduces retinal microembolization: a randomized
      clinical study using fluorescein angiography.
AB  - BACKGROUND: The use of minimized cardiopulmonary bypass (MCPB) circuits has
      recently increased in an attempt to reduce the adverse effects of CPB. This
      prospective randomized study aimed to determine the effects of MCPB on retinal
      microembolization and related inflammatory, coagulation, and endothelial markers
      compared with conventional extracorporeal circulation (CCPB) among patients
      undergoing coronary artery bypass graft surgery. METHODS: Forty patients entered,
      and 37 patients completed the study. After the induction of anesthesia and
      immediately after the termination of CPB, standardized retinal fluorescein
      angiographs and digital images were obtained on both eyes and analyzed in a
      blinded fashion in terms of the CPB circuit. Blood samples for inflammatory,
      coagulation, and endothelial markers were collected at eight time points until
      the third postoperative day. RESULTS: Postperfusion retinal fluorescein
      angiographs revealed microembolic perfusion defects in 2 of 18 in the MCPB group
      and in 9 of 18 in the CCPB group (p=0.027 [11% vs. 50%, difference 39%,
      confidence interval: 0.087 to 0.613, p=0.029]). Activation of polymorphonuclear
      leukocytes as measured with polymorphonuclear elastase was significantly
      decreased in the MCPB group. Other markers of inflammation, coagulation, and
      endothelial dysfunction increased comparably in both groups during CPB.
      CONCLUSIONS: Retinal microembolization was found to be decreased after the use of
      minimized CPB compared with CCPB, suggesting a decreased embolic load to the
      brain after MCPB.

PMID- 21172478
TI  - Invited commentary.

PMID- 21172479
TI  - Randomized flow capacity comparison of skeletonized and pedicled left internal
      mammary artery.
AB  - BACKGROUND: The preferential harvesting technique of the internal mammary artery
      has been periodically debated. This randomized study evaluated the flow outcome
      of the skeletonized versus pedicled left internal mammary artery. METHODS: Two
      hundred patients undergoing surgery for left anterior descending coronary artery
      revascularization were enrolled and randomized to pedicled (n=100) or
      skeletonized (n=100) harvesting. Intraoperative baseline flow and post adenosine
      infusion into the left ventricle, hospital outcome, echocardiographic results,
      and troponin I leakage were analyzed. Noninvasive periodic evaluation of flow was
      carried out at rest and during intravenous adenosine infusion by transthoracic
      Doppler ultrasound, and was stratified according to the harvesting technique.
      Final angiographic evaluation was performed by 64-slice multidetector computed
      tomography. RESULTS: Skeletonized left internal mammary arteries demonstrated
      better flow capacity at rest and during adenosine recruitment perioperatively and
      at all time points of follow-up. Troponin I leakage was significantly higher in
      the pedicled group (59 vs 42, p=0.02). Pedicled harvesting (hazard ratio [HR]
      3.6, 95% confidence interval [CI] 2.5 to 6.9, p<0.001); indexed left ventricular
      mass greater than 150 g/m2 (HR 4.6, 95% CI 3.1 to 7.5, p<0.001); and baseline
      corrected thrombolysis in myocardial infarction frame count greater than 30 (HR
      4.4, 95% CI, 3.8 to 7.2, p<0.001) were the most powerful multivariable predictors
      of graft flow reserve less than 2.0. Postoperative echocardiographic results and
      clinical and angiographic outcomes were comparable between the two groups.
      CONCLUSIONS: Skeletonization of the left internal mammary artery, beyond
      traditional proven advantages, provided significantly higher flow capacity and
      better graft flow reserve.

PMID- 21172480
TI  - Invited commentary.

PMID- 21172481
TI  - Results of completion arteriography after minimally invasive off-pump coronary
      artery bypass.
AB  - BACKGROUND: The benefits of a minimally invasive approach to off-pump coronary
      artery bypass remain controversial. The value of completion arteriography in
      validating this technique has not been investigated. METHODS: From April 2007 to
      October 2009, fifty-six patients underwent isolated minimally invasive coronary
      artery bypass grafting through a left thoracotomy without cardiopulmonary bypass.
      Forty-three of these patients underwent completion arteriography. RESULTS: Sixty
      five grafts were performed in these 56 patients, (average, 1.2 grafts per
      patient; range, 1 to 3). Forty-eight grafts were studied in the 43 patients
      undergoing completion arteriography. There were 4 findings on arteriogram leading
      to further immediate intervention (8.3%). These included 3 grafts with
      anastomotic stenoses or spasm requiring stent placement, and 1 patient who had
      limited dissection in the left internal mammary artery graft and underwent
      placement of an additional vein graft. These findings were independent of
      electrocardiographic changes or hemodynamic instability. The remainder of the
      studies showed no significant abnormalities. There were no deaths. One patient
      who did not have a completion arteriogram suffered a postoperative myocardial
      infarction requiring stent placement for anastomotic stenosis. Patients were
      discharged home an average of 6.8 days postoperatively. There were no instances
      of renal dysfunction postoperatively attributable to catheterization.
      CONCLUSIONS: Minimally invasive coronary artery bypass is safe and effective.
      Findings of completion arteriography occasionally reveal previously under
      recognized findings that, if corrected in a timely fashion, could potentially
      impact graft patency and clinical outcomes. Our experience validates this
      minimally invasive technique.

PMID- 21172482
TI  - Abdominal wall necrosis after harvest of both internal thoracic and inferior
      epigastric arteries.
AB  - BACKGROUND: The internal thoracic artery (ITA) and inferior epigastric artery
      (IEA) may be used as conduits for myocardial revascularization. Harvesting the
      ITAs and IEAs can lead to clinically significant ischemia of the anterior
      abdominal wall. METHODS: We created a registry with data from 108 patients
      receiving myocardial revascularization with 1 or greater ITA and (or) 1 or
      greater IEA. After revascularization, patients were followed to document their
      outcomes during hospitalization. We sought to identify risk factors for tissue
      necrosis in these patients. RESULTS: All patients had 1 (84%) or 2 (16%) IEAs
      harvested. Both ITAs were utilized in 81% of patients; 19% had only the left ITA
      harvested. All patients in whom 2 IEAs were harvested also had 2 ITAs harvested
      (17 of 108). Of these 17 patients, 2 (12%) developed abdominal wall necrosis.
      Only patients who had bilateral ITA and bilateral IEA harvest experienced this
      complication. CONCLUSIONS: Bilateral harvest of ITAs and IEAs results in a
      moderate risk of clinically significant abdominal wall necrosis. The extent of
      tissue loss may involve skin, muscle, and fascia, but the peritoneum and
      posterior rectus sheath remained intact in both affected patients in this series.
      These data may be most valuable to those who contemplate an abdominal operation
      in a patient who has had one or more of their ITAs or IEAs taken.

PMID- 21172483
TI  - Effect of body mass index on outcomes after cardiac surgery: is there an obesity
      paradox?
AB  - BACKGROUND: Numerous studies have documented an obesity paradox in which
      overweight and obese people with cardiovascular disease have a better prognosis
      compared with patients with normal body mass index (BMI). This study sought to
      quantify the effect of BMI on clinical outcomes after cardiac surgery and
      investigate the obesity paradox. METHODS: A concurrent cohort study of 2,440
      consecutive patients undergoing cardiac surgery (coronary artery bypass grafting
      [CABG], valve, or CABG and valve surgery) from January 2004 to December 2008 was
      carried out. The patients were divided into three groups on the basis of BMI:
      normal weight (BMI 18.5 to 24.9; n=556; 23%), overweight (BMI 25.0 to 29.9;
      n=965; 39%), and obese (BMI>=30; n=919; 38%). Multivariable analyses and
      propensity score matching were used to compare the early and late clinical
      outcomes among the different BMI groups. RESULTS: Overweight patients had a lower
      operative mortality (odds ratio, 0.4; 95% confidence interval, 0.2 to 0.9;
      p=0.031) compared with normal BMI patients. Obese patients had a comparable risk
      for operative mortality (odds ratio, 0.8; 95% confidence interval, 0.4 to 1.6;
      p=0.47) compared with normal-weight patients. Actuarial 5-year survival was
      better for the overweight (hazard ratio, 0.5; 95% confidence interval, 0.4 to
      0.8; p=0.002) and comparable for the obese (hazard ratio, 0.9; 95% confidence
      interval, 0.5 to 1.4; p=0.49) groups compared with the normal-weight patients.
      CONCLUSIONS: Overweight patients have better early hospital outcomes and improved
      survival after cardiac surgery compared with normal BMI patients, supporting the
      obesity paradox.

PMID- 21172484
TI  - Invited commentary.

PMID- 21172485
TI  - Outcomes of surgical aortic valve replacement in high-risk patients: a
      multiinstitutional study.
AB  - BACKGROUND: The introduction of transcatheter aortic valves has focused attention
      on outcomes after open aortic valve replacement (AVR) in very high-risk patients.
      This study analyzes the short-term and midterm outcomes of AVR in this patient
      cohort in the current surgical era. METHODS: A retrospective review was performed
      on 159 patients who underwent isolated, primary AVR with a STS PROM (Society of
      Thoracic Surgeons predicted risk of mortality) of 10% or greater from January
      2002 to December 2007 at four US academic institutions. Patients with previous
      valve operations were excluded. A multivariable model was constructed to
      determine predictors of in-hospital mortality. Estimates of the cumulative event
      rate mortality were calculated by the Kaplan-Meier method. RESULTS: The mean age
      of all patients was 76.1+/-11.2 years, most were men (92 of 159, 57.9%), and mean
      STS PROM was 16.3%+/-7.3%. Significant preoperative factors included the
      following: peripheral vascular disease, 33.3% (53 of 159); stroke, 23.3% (37 of
      159); renal failure, 50.3% (80 of 159); New York Heart Association class III-IV
      heart failure, 78.0% (124 of 159); and previous coronary artery bypass grafting,
      39.0% (62 of 159). Mean ejection fraction was 0.461+/-0.153 and median implanted
      valve size was 23 mm. Postoperative complications included the following: stroke,
      4.4% (7 of 159); heart block, 5.0% (8 of 159); multisystem organ failure, 6.9%
      (11 of 159); pneumonia, 7.5% (12 of 159); and dialysis, 8.2% (13 of 159).
      Postoperative length of stay was 12.6+/-11.0 days and in-hospital mortality was
      16.4% (26 of 159). One-, three-, and 5-year survival was 70.9%, 56.8%, and 47.4%,
      respectively. CONCLUSIONS: In the current era, high-risk surgical patients
      undergoing open AVR have respectable short and mid-term survival. These results
      should serve as a benchmark for evaluating outcomes of transcatheter aortic valve
      implantation.

PMID- 21172486
TI  - Transapical versus transfemoral aortic valve implantation: a comparison of
      survival and safety.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a therapeutic
      option for high-risk patients with aortic stenosis. Procedural mortality remains
      high in comparison with conventional aortic valve replacement (AVR) because
      patients determined for TAVI are commonly denied conventional surgery. We aimed
      to evaluate access-related complications between the transfemoral (TF) and the
      transapical (TA) approach and to compare survival between TAVI and conventional
      AVR in propensity-score-matched patients. METHODS: Between January 2008 and
      November 2009, 40 patients underwent TAVI (TF, n=10; TA, n=30) with the Edwards
      Sapien bioprosthesis (Edwards Lifesciences, Irvine, CA). Survival and
      postoperative complications were evaluated between the TF and the TA approach. A
      comparison of survival was made between the TAVI patients and propensity-score
      matched patients undergoing conventional AVR. RESULTS: Successful implantation
      rate was 92.5% (37 of 40). Thirty-day mortality was 5.0% (2 of 40), and the
      overall in-hospital mortality was 10.0% (4 of 40). Survival after TAVI was 77% at
      both 6 months and 1 year. Major vascular complications occurred in 3 of 10
      patients (all in the TF group), and 3 of 40 patients (7.5%) suffered
      cerebrovascular events. A comparison of survival between TAVI and propensity
      score-matched conventional AVR patients showed no significant difference in
      either the TA group (p=0.73) or the TF group (p=0.59). CONCLUSIONS: The vascular
      complications occurring when using the TF approach were probably related to a
      combination of a wide introducer sheath and heavily calcified femoral arteries in
      a high-risk population. No serious complications were encountered when using the
      TA approach. After propensity-score matching, survival with both the TA and TF
      approaches is similar to that after AVR.

PMID- 21172487
TI  - The Ross procedure performed for aortic insufficiency is associated with
      increased autograft reoperation.
AB  - BACKGROUND: The Ross procedure in infants/children is generally accepted, while
      in adults it remains controversial. We examined our adult experience for clinical
      and operative factors that predict autograft reoperation. METHODS: Prospectively
      collected data of 160 consecutive adults undergoing a Ross procedure by a single
      surgeon from July 1994 through June 2008 were reviewed. Clinical follow-up was
      obtained in 160 of 160 (100%) and echocardiogram in 150 of 152 (98.7%) survivors.
      Multivariate proportional hazards analysis was employed to determine risk factors
      for autograft reoperation. RESULTS: Mean age was 42.0+/-11.1 years and 73.1% were
      male. Presenting pathology was aortic insufficiency (AI) in 93 (58.1%) and aortic
      stenosis (AS) in 67 (41.9%). Bicuspid aortic valves accounted for 91% of AS and
      85% of AI patients. Annuloplasty was required in 49 of 93 (52.7%) patients with
      AI and 12 of 67 (17.9%) patients with AS (p<0.001). There were 3 operative
      mortalities (1.87%) with 2 late cardiac related deaths (1.3%). Kaplan-Meier
      survival was 92.9+/-0.03% at 7.5 years. Fifteen patients (9.4%) required
      reoperation on the autograft root; 14 of 15 (93.3%) had AI. The time to aortic
      valve reoperation significantly diverged at 7.5 years; patients with AI required
      more reoperations. Factors predicting increased risk of autograft reoperation
      included female gender (hazard ratio [HR]=7.7; 95% confidence interval [CI] 1.3
      to 46.6), aortic dilatation (HR=6.3; 95% CI 1.3 to 33.2), a 3-cusp valve (HR=8.1;
      95% CI 1.3 to 53.3) and annuloplasty (HR=7.8; 95% CI 1.2 to 52.0). CONCLUSIONS:
      The Ross procedure in adults provides excellent freedom from autograft failure in
      patients operated for AS. Other treatment alternatives should be strongly
      considered in adults presenting primarily with aortic insufficiency.

PMID- 21172488
TI  - Aortic valve replacement with 17-mm mechanical prostheses: is patient-prosthesis
      mismatch a relevant phenomenon?
AB  - BACKGROUND: We sought to evaluate the long-term performance of a consecutive
      cohort of patients implanted with a 17-mm bileaflet mechanical prosthesis.
      METHODS: Between January 1995 and December 2005, 78 patients (74 women, mean
      age=71+/-12 years) underwent aortic valve replacement with a 17-mm mechanical
      bileaflet prosthesis (Sorin Bicarbon-Slim and St. Jude Medical-HP). Preoperative
      mean body surface area and New York Heart Association class were 1.6+/-0.2 m2 and
      2.6+/-0.8, respectively. Preoperative mean aortic annulus, indexed aortic valve
      area, and peak and mean gradients were 18+/-1.6 mm, 0.42 cm2/m2, 89+/-32 mm Hg,
      and 56+/-21 mm Hg, respectively. Patients were divided into two groups, according
      to the presence (group A, 29 patients) or absence of patient-prosthesis mismatch
      (group B, 49 patients). Patient-prosthesis mismatch was defined by an indexed
      effective orifice area less than 0.85 cm2/m2. RESULTS: Overall hospital mortality
      was 8.8%. Follow-up time averaged 86+/-44 months. Actuarial 5-year and 10-year
      survival rates were 83.7% and 65.3%, respectively. The mean postoperative New
      York Heart Association class was 1.3+/-0.6 (p<0.001). Overall indexed left
      ventricular mass decreased from 163+/-48 to 120+/-42 g/m2 (p<0.001), whereas
      average peak and mean prosthesis gradients were 28+/-9 mm Hg and 15+/-6 mm Hg,
      respectively (p<0.001). Early and long-term mortality were similar between the
      two groups as well as long-term hemodynamic performance (mean peak gradient was
      28 mm Hg and 27 mm Hg in group A and B, respectively, not significant); left
      ventricular mass regression occurred similarly in both groups (indexed left
      ventricular mass at follow-up was 136+/-48 and 113+/-40 in group A and B,
      respectively; not significant). CONCLUSIONS: Selected patients with aortic
      stenosis experience satisfactory clinical improvement after aortic valve
      replacement with modern small-diameter bileaflet prostheses.

PMID- 21172489
TI  - Invited commentary.

PMID- 21172490
TI  - Outcomes of minimally invasive valve surgery versus median sternotomy in patients
      age 75 years or greater.
AB  - BACKGROUND: Advanced age is a major predictor of poor outcome in patients
      undergoing valve surgery. We hypothesized that elderly patients who underwent
      minimally invasive valve surgery for aortic or mitral valve disease would do
      better when compared with those undergoing the standard median sternotomy.
      METHODS: We retrospectively reviewed 2,107 consecutive heart operations at our
      institution and identified 203 patients, age 75 years or greater, who underwent
      isolated mitral or aortic valve surgery. Outcomes of those who had minimally
      invasive valve surgery through a right minithoracotomy were compared with those
      who had a median sternotomy. RESULTS: Of the 203 patients, 119 (59%) underwent a
      minimally invasive approach, while 84 (41%) had a median sternotomy. The median
      postoperative length of stay was 7 days (interquartile range [IQR] 6 to 10)
      versus 12 days (IQR 9 to 20), p less than 0.001, and intensive care unit length
      of stay was 52 hours (IQR 44 to 93) versus 119 hours (IQR 57 to 193), p less than
      0.001 for minimally invasive and median sternotomy, respectively. In-hospital
      mortality was 2 (1.7%) versus 8 (9.5%, p=0.01 and composite postoperative
      morbidity and mortality occurred in 25 (21%) versus 38 (45.2%), p less than
      0.001, in minimally invasive versus median sternotomy, respectively. The
      difference was driven by the following: a lower incidence of acute renal failure,
      1 (0.8%) versus 14 (16.7%), p<0.001; prolonged intubation 23 (19.3%) versus 32
      (38.1%), p=0.003; wound infections 1 (0.8%) versus 5 (6%), p=0.034; and death.
      CONCLUSIONS: Minimally invasive surgery for isolated valve lesions in elderly
      patients yields a lower morbidity and mortality when compared with median
      sternotomy and should be considered when such individuals require valve surgery.

PMID- 21172491
TI  - Endovascular stent-graft repair of late pseudoaneurysms after surgery for aortic
      coarctation.
AB  - BACKGROUND: We analyzed the potential of endovascular stent grafts to treat late
      aortic pseudoaneurysms after coarctation repair. METHODS: Eight patients (7 male;
      age 28 to 58, mean 43 years) presented with aortic pseudoaneurysms after primary
      repair performed at the age of 5 to 27 (mean 12) years; 2 patients had rupture
      with hemorrhagic shock. The mean interval between the procedures was 31 (19 to
      42) years; one patient had 3 previous operations. This subset represents 2.2% of
      our overall experience in thoracic endovascular repair (n=368). Thoracic
      endografts were implanted using the transfemoral technique. Custom-made reverse
      tapered stent grafts were used in 4 cases. The left subclavian artery (LSA) was
      covered in 5 patients. Protective transposition of the left subclavian artery was
      performed in 4 patients. RESULTS: Hospital mortality was 12.5%; 1 patient died
      from secondary rupture after emergency repair. Primary complete exclusion of the
      aneurysm was achieved in 6 patients. Secondary exclusion after implantation of a
      second stent graft was successful in the second rupture patient. No endoleak was
      present at discharge. All discharged patients are alive after 8 to 63 (mean 36)
      months. Follow-up computed tomography or transesophageal echocardiography
      revealed no secondary endoleaks or late expansion. The pseudoaneurysms had shrunk
      completely in 3 patients, were reduced in size in 2 patients, and remained
      unchanged in 2 patients. No late secondary interventions were noted. CONCLUSIONS:
      Single piece, reversed, tapered stent grafts adapt better to the special anatomy
      of the hypoplastic aortic arch. Midterm results are excellent; complete shrinkage
      in 50% is remarkable. However, the long-term behavior of these implants in young
      patients requires further evaluation and surveillance.

PMID- 21172492
TI  - Compliance of the Valsalva graft's pseudosinuses at midterm follow-up with
      cardiovascular magnetic resonance.
AB  - BACKGROUND: In previous studies, the Valsalva graft's compliance at the level of
      the Dacron pseudosinuses was found similar to that of normal sinuses shortly (2+/
      1 months) after the operation. We sought to investigate with cardiac magnetic
      resonance the compliance of the Valsalva graft pseudosinuses at midterm follow
      up. METHODS: Seven patients (group A) and 7 age-matched controls (group B) were
      studied with steady-state free precession and phase-contrast cardiac magnetic
      resonance for aortic root and ascending aorta evaluation. Blood pressure was
      measured during phase-contrast acquisition to derive the following mechanical
      properties of the vascular prosthesis: pulsatility, compliance, distensibility,
      and elastic modulus. RESULTS: Mean postoperative follow-up was 55+/-9.84 months.
      Mean age was 69.2+/-4.98 years in group A, and 65.7+/-7.16 years in group B. All
      the studied variables were coherent in showing a significant difference between
      the two groups, and between aortic root (skirt portion of the graft) and
      ascending aorta (tubular part of the graft) in group A. The presence of
      periaortic fibrosis did not show any correlation with the ascending aorta's
      mechanical properties. CONCLUSIONS: At midterm follow-up, the pseudosinuses
      compliance of the Valsalva graft is still appreciable and significantly greater
      than the tubular portion.

PMID- 21172493
TI  - Invited commentary.

PMID- 21172494
TI  - Left atrial ganglion ablation as an adjunct to atrial fibrillation surgery in
      valvular heart disease.
AB  - BACKGROUND: Our aim was to evaluate early results of ganglionic plexus (GP)
      ablation with modified Cox maze lesion sets for concomitant atrial fibrillation
      (AF) during corrective valve surgery. METHODS: Between December 2006 and April
      2008, 20 patients (7 men; median age, 65 years; range, 52 to 82 years) with
      valvular heart disease and AF (intermittent in 12 [60%]) underwent corrective
      valve surgery with maze and GP ablation. Patients were then compared with a case
      matched control cohort who underwent radiofrequency ablation maze alone. RESULTS:
      Procedures included mitral valve repair in 7 patients (35%), multivalve
      procedures in 5 (25%), mitral valve replacement in 4 (20%), aortic valve
      replacement in 3 (15%), and valve-sparing aortic root replacement in 1 (5%). All
      patients underwent concomitant AF ablation procedures (biatrial maze in 11 [55%],
      left-sided maze in 9 [45%]). Ganglionic plexus stimulation was performed in all
      patients. Sites at which the R-R interval doubled were considered active and were
      ablated. There were no early deaths. Freedom from AF at 1 year was significantly
      higher (90% versus 50%; p=0.01) and mean New York Heart Association functional
      class was better (1 versus 1.7; p<0.001) in the group that underwent maze and GP
      ablation compared with maze alone. CONCLUSIONS: Active left atrial GP are
      frequently present in patients with AF and valvular heart disease, and GP
      ablation can be safely performed as an adjunct to AF ablation during valve
      surgery. Early results are promising and may yield higher freedom from AF
      compared with radiofrequency ablation maze alone.

PMID- 21172495
TI  - Invited commentary.

PMID- 21172496
TI  - The impact of volume reduction on early and long-term outcomes in surgical
      ventricular restoration for severe heart failure.
AB  - BACKGROUND: Recent published results suggest no additive benefit to surgical
      ventricular restoration (SVR) when combined with coronary artery bypass grafting.
      However, there may still be a subgroup of patients with severe heart failure who
      can benefit from this procedure. We reviewed our institutional experience with
      SVR to determine early and late outcomes based on volume reduction. METHODS: We
      retrospectively reviewed our SVR patients (January 2002 to April 2008) with
      follow-up to March 2009. Baseline comorbidities, operative data, and
      postoperative outcomes were assessed by chart review, phone calls, and mailings.
      Survival was modeled using the Kaplan-Meier method. Cardiac magnetic resonance
      imaging, myocardial perfusion scans, and echocardiography assessed cardiac
      function, candidacy for SVR, and volume reduction. RESULTS: We reviewed 87
      consecutive SVR patients (69 men). Mean age at operation was 61.1 years.
      Preoperatively, all patients had congestive heart failure, with 80 (92%) at New
      York Heart Association III/IV. All patients underwent preoperative viability
      studies. Three-vessel occlusion exceeding 50% was present in 69 (79%). After SVR,
      ejection fraction improved from 0.236 to 0.332 (p<0.001). Preoperative and
      postoperative magnetic resonance imaging in 26 patients (30.0%) showed a 30.8%
      reduction in left ventricular end systolic volume index. At follow-up, 51 of 66
      (77%) improved to New York Heart Association I/II. One intraoperative death
      occurred. Preoperative left ventricular end systolic volume index of 80 to 120
      was associated with improved survival (73% at 3 years). CONCLUSIONS: SVR is a
      surgical option for appropriately selected patients with severe congestive heart
      failure. In these high-risk patients, SVR successfully increased ejection
      fraction and decreased symptoms. A left ventricular end systolic volume index of
      80 to 120 may be the ideal range for SVR procedures.

PMID- 21172497
TI  - Three-dimensional echocardiography for the preoperative assessment of patients
      with left ventricular aneurysm.
AB  - BACKGROUND: Surgical ventricular reconstruction has been proposed as a treatment
      option in heart failure patients with left ventricular (LV) aneurysm. The
      feasibility of this procedure has some limitations, and extensive preoperative
      evaluation is necessary to give the correct indication. For this purpose,
      magnetic resonance imaging (MRI) is currently considered the gold standard,
      providing accurate quantification of LV shape, size, and global and regional
      function together with the assessment of myocardial scar and mitral regurgitation
      severity. The aim of this study was to evaluate the accuracy of real-time three
      dimensional echocardiography (RT3DE) as a potential alternative to MRI for this
      evaluation. METHODS: A total of 52 patients with ischemic cardiomyopathy and LV
      aneurysm underwent a comprehensive analysis with two-dimensional
      echocardiography, RT3DE, and MRI. RESULTS: Excellent correlation (r=0.97,
      p<0.001) and agreement were found between RT3DE and MRI for quantification of LV
      volumes, ejection fraction, and sphericity index; in a segment-to-segment
      comparison, RT3DE was shown to be accurate also for the analysis of wall motion
      abnormalities (k=0.62) and LV regional thickness (k=0.56) as a marker of
      myocardial scar. In contrast, two-dimensional echocardiography significantly
      underestimated these variables. Furthermore, mitral regurgitant volume assessed
      by RT3DE showed excellent correlation (r=0.93) with regurgitant volume measured
      by MRI, without significant bias (=-0.7 mL/beat). CONCLUSIONS: In the management
      of heart failure patients with LV aneurysm, RT3DE provides an accurate and
      comprehensive assessment, including quantification of LV size, shape, global
      systolic function, regional wall motion, and myocardial scar together with
      precise evaluation of the severity of mitral regurgitation.

PMID- 21172498
TI  - Invited commentary.

PMID- 21172499
TI  - Multiple electrode whole-blood aggregometry and bleeding in cardiac surgery
      patients receiving thienopyridines.
AB  - BACKGROUND: Preoperative treatment with thienopyridines is associated with
      increased postoperative bleeding in cardiac surgery patients. Patients under
      treatment with thienopyridines have different levels of platelet dysfunction and
      the effects of discontinuation are not totally predictable. The present study
      aimed to determine if a preoperative assessment of platelet function in these
      patients could provide clinically relevant information regarding the risks of
      excessive postoperative bleeding and transfusion requirements. METHODS: This is a
      retrospective analysis of prospectively collected data. Patients (n=87) under
      thienopyridine treatment until at least one week before cardiac surgery were
      enrolled in the study. Platelet function was assessed preoperatively with
      multiple electrode aggregometry: the adenosine diphosphate (ADP) test and TRAP
      (thrombin receptor-associated peptide) test were performed for all patients.
      RESULTS: Univariate analysis revealed that postoperative bleeding was associated
      (p<0.1) with preoperative serum creatinine level, platelet count, CPB
      (cardiopulmonary bypass) duration, and results from the ADP test and the TRAP
      test. Multivariable linear regression analysis confirmed the CPB duration
      (p=0.049) and ADP test (p=0.007) as independently associated with postoperative
      bleeding. The relationship between the ADP test and postoperative bleeding was
      investigated with polynomial regression analysis, and a logarithmic equation
      provided the best fit. The accuracy of prediction was good (area under the curve
      0.71, p=0.013), with a cutoff value for the ADP test at 31 U (sensitivity 72%,
      specificity 66%, negative predictive value 92%, and positive predictive value
      29%). CONCLUSIONS: The multiple electrode aggregometry ADP test in patients under
      thienopyridine treatment and undergoing cardiac surgery is associated with
      postoperative bleeding and platelet transfusion and provides an accurate
      preoperative prediction of postoperative bleeding risk.

PMID- 21172500
TI  - Invited commentary.

PMID- 21172501
TI  - Outcomes of off-pump aortic valve bypass surgery for the relief of aortic
      stenosis in adults.
AB  - BACKGROUND: Elderly patients with aortic stenosis presenting for an aortic valve
      replacement with a hostile ascending aorta remain a challenging patient cohort.
      The purpose of this study was to assess outcomes after the use of an aortic valve
      bypass performed without cardiopulmonary bypass. METHODS: A retrospective review
      was performed on 21 high-risk patients who underwent primary, isolated aortic
      valve bypass from September 2004 to June 2009 at Emory Healthcare Hospitals.
      Aortic valve bypass was used for a porcelain aorta alone in 6 (28.6%) patients,
      previous coronary artery bypass grafting in 4 (19.0%), or both in 10 (47.6%). One
      patient (4.8%) was thought not to be a candidate for cardiopulmonary bypass
      secondary to a severe cirrhosis. RESULTS: Mean age was 73.9+/-7.0 years (median,
      75.0 years), and 15 patients (71.4%) were male. Mean New York Heart Association
      classification was 3.0+/-1.0 (median, 3.0), and preoperative ejection fraction
      was 0.460+/-0.163 (median, 0.500). Preoperative comorbidities included peripheral
      vascular disease (n=10; 47.6%), chronic lung disease (n=16; 76.2%), diabetes
      mellitus (n=10; 47.6%), and dialysis-dependence (n=2; 9.5%). Either an 18-mm
      (n=11; 52.4%) or 20-mm (n=10; 47.6%) conduit was used, with an interposed
      Freestyle 21 porcine root in all patients. All operations were performed without
      cardiopulmonary bypass. There were no intraoperative mortalities. The mean
      intensive care unit stay was 133.7+/-161.3 hours (median, 80.2 hours), and
      overall postoperative length of stay was 12.9+/-10.8 days (median, 9.0 days). In
      hospital mortality occurred in 3 patients (14.3%). Mid-term follow-up shows an
      additional 4 patients died at a median follow-up of 1.3 years. CONCLUSIONS:
      Aortic valve bypass without cardiopulmonary bypass is a feasible alternative for
      the treatment of severe aortic stenosis with acceptable short-term morbidity and
      minimal mortality in this extremely high-risk surgical population.

PMID- 21172502
TI  - Prognosis of patients on extracorporeal membrane oxygenation: the impact of acute
      kidney injury on mortality.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been utilized for
      patients in critical condition, such as those with life-threatening respiratory
      failure or postcardiotomy cardiogenic shock. This study analyzed the outcomes of
      patients treated with ECMO and identified the relationship between prognosis and
      the Acute Kidney Injury Network (AKIN) scores obtained at pre-ECMO support (AKIN0
      hour); and at post-ECMO support 24 hours (AKIN24-hour) and 48 hours (AKIN48
      hour). METHODS: This study reviewed the medical records of 102 critically ill
      patients on ECMO support at a specialized intensive care unit at a tertiary care
      university hospital between March 2002 and January 2008. Demographic, clinical,
      and laboratory variables were retrospectively collected as survival predicators.
      RESULTS: The overall mortality rate was 57.8%. The most common condition
      requiring ECMO support was cardiogenic shock. Goodness-of-fit was good for AKIN0
      hour, AKIN24-hour, and AKIN48-hour criteria. The AKIN0-hour, AKIN24-hour, and
      AKIN48-hour scoring systems also had excellent areas under the receiver operating
      characteristic curve (0.804+/-0.046, 0.811+/-0.045, and 0.858+/-0.040,
      respectively). Furthermore, multiple logistic regression analysis indicated that
      AKIN48-hour, age, and Glasgow Coma Scale score on the first day of intensive care
      unit admission were independent risk factors for hospital mortality. Finally,
      cumulative survival rates at 6-month follow-up after hospital discharge differed
      significantly (p<0.05) for AKIN48-hour stage 0 versus AKIN48-hour stages 1, 2,
      and 3; and AKIN48-hour stage 1 and 2 versus AKIN48-hour stage 3. CONCLUSIONS:
      During ECMO support, the AKIN48-hour scoring system proved to be a reproducible
      evaluation tool with excellent prognostic abilities for these patients.

PMID- 21172503
TI  - Invited commentary.

PMID- 21172504
TI  - Use of venovenous extracorporeal membrane oxygenation and an atrial septostomy
      for pulmonary and right ventricular failure.
AB  - BACKGROUND: Right ventricular failure is a major contributor to morbidity and
      mortality on the lung transplant waiting list. This study was designed to
      evaluate the effectiveness of an atrial septostomy with venovenous extracorporeal
      membrane oxygenation (VV-ECMO) as a novel potential bridge to transplantation.
      METHODS: Adult sheep (58+/-3 kg; n=12) underwent a clamshell thoracotomy and
      instrumentation to measure all relevant pressures and cardiac output (CO). Sheep
      with tricuspid insufficiency (TI [n=5]) and without tricuspid insufficiency (OTI
      [n=7]) were examined. After creation of a 1-cm atrial septal defect and
      initiating VV-ECMO, the pulmonary artery (PA) was banded to allow progressive
      reduction of pulmonary blood flow, and data were collected. RESULTS: The CO in
      both groups remained unchanged from baseline at all pulmonary blood flow
      conditions. With TI, the CO was 5.1+/-1.2 L/min at baseline versus 5.1+/-1.2
      L/min with a fully occluded PA (p=0.99). For OTI, the CO was 4.5+/-1.4 L/min at
      baseline versus 4.5+/-1.2 L/min with no pulmonary blood flow (p=0.99).
      Furthermore, CO was not affected by the presence of TI (p=0.76). Mean right
      ventricular pressures were significantly lower in the TI group (TI=20.2+/-11 mm
      Hg versus OTI=29.9+/-8.9 mm Hg; p<0.00001). Right and left atrial mean arterial
      pressures were not different between both groups (p>0.5). Lastly, VV-ECMO
      maintained normal blood gases, with mean O2 saturations of 99% +/- 4.1% in both
      groups. CONCLUSIONS: Right to left atrial shunting of oxygenated blood with VV
      ECMO is capable of maintaining normal systemic hemodynamics and normal arterial
      blood gases during high right ventricular afterload dysfunction.

PMID- 21172505
TI  - Comparison of the Young-Laplace law and finite element based calculation of
      ventricular wall stress: implications for postinfarct and surgical ventricular
      remodeling.
AB  - BACKGROUND: Both the Young-Laplace law and finite element (FE) based methods have
      been used to calculate left ventricular wall stress. We tested the hypothesis
      that the Young-Laplace law is able to reproduce results obtained with the FE
      method. METHODS: Magnetic resonance imaging scans with noninvasive tags were used
      to calculate three-dimensional myocardial strain in 5 sheep 16 weeks after
      anteroapical myocardial infarction, and in 1 of those sheep 6 weeks after a Dor
      procedure. Animal-specific FE models were created from the remaining 5 animals
      using magnetic resonance images obtained at early diastolic filling. The FE-based
      stress in the fiber, cross-fiber, and circumferential directions was calculated
      and compared to stress calculated with the assumption that wall thickness is very
      much less than the radius of curvature (Young-Laplace law), and without that
      assumption (modified Laplace). RESULTS: First, circumferential stress calculated
      with the modified Laplace law is closer to results obtained with the FE method
      than stress calculated with the Young-Laplace law. However, there are pronounced
      regional differences, with the largest difference between modified Laplace and FE
      occurring in the inner and outer layers of the infarct borderzone. Also, stress
      calculated with the modified Laplace is very different than stress in the fiber
      and cross-fiber direction calculated with FE. As a consequence, the modified
      Laplace law is inaccurate when used to calculate the effect of the Dor procedure
      on regional ventricular stress. CONCLUSIONS: The FE method is necessary to
      determine stress in the left ventricle with postinfarct and surgical ventricular
      remodeling.

PMID- 21172507
TI  - Quantitative mitral valve modeling using real-time three-dimensional
      echocardiography: technique and repeatability.
AB  - BACKGROUND: Real-time three-dimensional (3D) echocardiography has the ability to
      construct quantitative models of the mitral valve (MV). Imaging and modeling
      algorithms rely on operator interpretation of raw images and may be subject to
      observer-dependent variability. We describe a comprehensive analysis technique to
      generate high-resolution 3D MV models and examine interoperator and intraoperator
      repeatability in humans. METHODS: Patients with normal MVs were imaged using
      intraoperative transesophageal real-time 3D echocardiography. The annulus and
      leaflets were manually segmented using a TomTec Echo-View workstation. The
      resultant annular and leaflet point cloud was used to generate fully quantitative
      3D MV models using custom Matlab algorithms. Eight images were subjected to
      analysis by two independent observers. Two sequential images were acquired for 6
      patients and analyzed by the same observer. Each pair of annular tracings was
      compared with respect to conventional variables and by calculating the mean
      absolute distance between paired renderings. To compare leaflets, MV models were
      aligned so as to minimize their sum of squares difference, and their mean
      absolute difference was measured. RESULTS: Mean absolute annular and leaflet
      distance was 2.4+/-0.8 and 0.6+/-0.2 mm for the interobserver and 1.5+/-0.6 and
      0.5+/-0.2 mm for the intraobserver comparisons, respectively. There was less than
      10% variation in annular variables between comparisons. CONCLUSIONS: These
      techniques generate high-resolution, quantitative 3D models of the MV and can be
      used consistently to image the human MV with very small interoperator and
      intraoperator variability. These data lay the framework for reliable and
      comprehensive noninvasive modeling of the normal and diseased MV.

PMID- 21172506
TI  - Ischemic mitral regurgitation: a quantitative three-dimensional echocardiographic
      analysis.
AB  - BACKGROUND: A comprehensive three-dimensional echocardiography based approach is
      applied to preoperative mitral valve (MV) analysis in patients with ischemic
      mitral regurgitation (IMR). This method is used to characterize the heterogeneous
      nature of the pathologic anatomy associated with IMR. METHODS: Intraoperative
      real-time three-dimensional transesophageal echocardiograms of 18 patients with
      IMR (10 with anterior, 8 with inferior infarcts) and 17 patients with normal MV
      were analyzed. A customized image analysis protocol was used to assess global and
      regional determinants of annular size and shape, leaflet tethering and curvature,
      relative papillary muscle anatomy, and anatomic regurgitant orifice area.
      RESULTS: Both mitral annular area and MV tenting volume were increased in the IMR
      group as compared with patients with normal MV (mitral annular area=1,065+/-59
      mm2 versus 779+/-44 mm2, p=0.001; and MV tenting volume=3,413+/-403 mm3 versus
      1,696+/-200 mm3, p=0.001, respectively). Within the IMR group, patients with
      anterior infarct had larger annuli (1,168+/-99 mm2) and greater tenting volumes
      (4,260+/-779 mm3 versus 2,735+/-245 mm3, p=0.06) than the inferior infarct
      subgroup. Papillary-annular distance was increased in the IMR group relative to
      normal; these distances were largest in patients with anterior infarcts. Whereas
      patients with normal MV had very consistent anatomic determinants, annular shape
      and leaflet tenting distribution in the IMR group were exceedingly variable. Mean
      anatomic regurgitant orifice area was 25.8+/-3.0 mm2, and the number of discrete
      regurgitant orifices varied from 1 to 4. CONCLUSIONS: Application of custom
      analysis techniques to three-dimensional echocardiography images allows a
      quantitative and systematic analysis of the MV, and demonstrates the extreme
      variability in pathologic anatomy that occurs in patients with severe IMR.

PMID- 21172508
TI  - Ventricular performance in long-term survivors after Fontan operation.
AB  - BACKGROUND: Ventricular function and arrhythmia in patients with Fontan
      circulation in long-term follow-up are still unknown. METHODS: We retrospectively
      reviewed 48 patients who survived and were followed up for more than 15 years,
      among 110 patients who underwent Fontan operation in our institute from 1979 to
      1992. Atriopulmonary connection was performed in 26 patients and total
      cavopulmonary connection in 22. The patients were categorized into right
      ventricle, left ventricle, and biventricle groups. Follow-up cardiac
      catheterization and exercise test were performed routinely every 5 years post
      surgery. Median age at Fontan operation was 5 years. RESULTS: Mean follow-up was
      18.5 years. Cardiac index in the total cavopulmonary connection group was higher
      than in the atriopulmonary connection group at 10 and 15 years post surgery
      (p<0.05). Ejection fraction in the left-ventricle group was higher than in the
      right-ventricle group. End-diastolic volume at 5, 10, and 15 years was
      significantly lower than at 1 year (p<0.05). End-diastolic pressure at 10 years
      was significantly higher than at 1 and 5 years (p<0.05). Beyond 15 years, 6
      patients developed ventricular tachycardia. The only significant risk factors for
      the onset of ventricular tachycardia in a multivariate analysis were age at
      Fontan operation and absolute age (p<0.05). CONCLUSIONS: Long-term follow-up of
      patients demonstrated that postoperative ventricular systolic performance seemed
      to become steady. Ventricular tachycardia was detected 15 years post surgery,
      especially in older patients with older age at Fontan operation, possibly
      revealing a risk factor in the long-term postoperative period, thereby meriting
      further consideration.

PMID- 21172509
TI  - Do patients with complete transposition of the great arteries and severe
      pulmonary hypertension benefit from an arterial switch operation?
AB  - BACKGROUND: Whether an arterial switch operation benefits patients with
      transposition of the great arteries and severe pulmonary hypertension (PH)
      remains controversial. Therefore, we evaluated the relationship between
      preoperative PH and early and midterm clinical outcomes after an arterial switch
      procedure. METHODS: In this retrospective study, 101 consecutive patients with
      transposition of the great arteries underwent an arterial switch operation
      between February 2004 and October 2007. Seventy had a ventricular septal defect
      as well; patients with intact ventricular septum and complicated concomitant
      abnormities were excluded. Preoperative medical records were reviewed and mean
      follow-up was 22.4+/-15.2 months. After sternotomy, we directly measured
      pulmonary artery pressure before and after instituting extracorporeal
      circulation. Patients were divided into three groups according to mean pulmonary
      artery pressure (mPAP): control group (mPAP<25 mm Hg, n=23), moderate PH group
      (mPAP 25 to 50 mm Hg, n=37), and severe PH group (mPAP>=50 mm Hg, n=10). Early
      and midterm results were compared among groups. RESULTS: Postoperatively,
      pulmonary artery pressure of both the moderate and severe PH groups decreased
      significantly. There were no significant differences in occurrence of
      postoperative complications or in-hospital mortality in the three groups (control
      group, 8.7%; moderate PH group, 8.1%; severe PH group, 10%; p=0.98). However,
      midterm mortality differed significantly (control group, 4.3%; moderate PH group,
      2.7%; severe PH group, 40%; p<0.01). CONCLUSIONS: Patients with transposition of
      the great arteries and mPAP less than 50 mm Hg can achieve satisfying results
      after an arterial switch operation. However, even though the operation can
      decrease pulmonary artery pressure, patients with preoperative mPAP greater than
      50 mm Hg still suffer from high midterm mortality.

PMID- 21172510
TI  - Invited commentary.

PMID- 21172511
TI  - Rastelli operation for transposition of the great arteries with ventricular
      septal defect and pulmonary stenosis.
AB  - BACKGROUND: The optimal surgical treatment of patients with transposition of the
      great arteries, ventricular septal defect, and pulmonary stenosis is
      controversial. Although the Rastelli operation has been standard surgical
      management of this lesion, aortic root translocation with right ventricular
      outflow tract (RVOT) reconstruction (Nikaidoh) and the pulmonary artery
      translocation (Lecompte) or REV (reparation a l'etage ventriculaire) are surgical
      alternatives more recently introduced to treat this complex lesion. This report
      reviews our 20-year experience with the Rastelli procedure and attempts to
      compare our outcomes with those recently published using the Nikaidoh and REV
      procedures. METHODS: Between 1988 and 2008, 40 patients (median age, 4 years;
      range, 9 months to 17 years) underwent Rastelli operation at our institutions.
      The RVOT was obstructed in 32 and atretic in 8. Follow-up was available for all
      but one patient (mean follow-up, 8.6+/-5.6 years). The RVOT was reconstructed
      with homograft (n=25), bovine jugular vein (n=8), nonvalved Dacron tube (n=5), or
      a porcine valved conduit (n=2). Two patients required a pacemaker. RESULTS: There
      were no early, but three late deaths and one heart transplantation 12 years
      postoperative the Rastelli operation. Kaplan-Meier survival was 93% at 5, 10, and
      20 years. Univariate risk factors for death or transplantation included surgery
      before 1998 (p=0.03) and concomitant noncardiac anomalies (p=0.001). Sixteen
      patients (40%) had reoperation for right ventricular-pulmonary artery conduit
      stenosis (mean, 7.8+/-3.8 years) without mortality. Freedom from conduit
      replacement was 86%, 74%, 63%, and 59% at 5, 10, 15, and 20 years, respectively.
      Multivariate analysis revealed that the risk factors of conduit replacement were
      younger age at operation (p=0.001) and surgery before 1998 (p<0.001). Two
      patients (5%) required reoperation for left ventricular outflow tract
      obstruction. At follow-up, there were no sudden unexplained deaths, and New York
      Heart Association functional class is I or II. CONCLUSIONS: The Rastelli
      procedure is a low-risk operation with regard to early and late mortality and
      reoperation for left ventricular outflow tract obstruction. Conduit change
      operations will be required in most patients regardless of the technique of
      repair, but currently can be performed with low morbidity and mortality. These
      midterm outcomes after the Rastelli operation should serve as a basis for
      comparison with surgical alternatives more recently introduced for transposition
      of the great arteries and ventricular septal defect with RVOT obstruction.

PMID- 21172512
TI  - Risk factor analysis of 170 single-institutional contegra implantations in
      pulmonary position.
AB  - BACKGROUND: The aim of this study is to evaluate risk factors affecting survival
      of Contegra grafts used in the pulmonary position. METHODS: One hundred seventy
      Contegra implanted (2001 to 2007) in the pulmonary position for replacement after
      a prior repair (90), Ross procedure (29), tetralogy of Fallot and variants (22),
      truncus arteriosus (13), Rastelli procedure (8), and miscellaneous (8) were
      reviewed. Median age was 107 (0.1 to 894) months. Follow-up was 96% complete with
      a median duration of 65 (7 to 98) months. RESULTS: There were 7 early and 6 late
      deaths (none Contegra related) with a survival of 92%+/-2% at 98 months. Thirty
      four Contegra were replaced at a median duration of 43 (7 to 82) months. Eight of
      28 balloon-dilated Contegra remain palliated at 49 (23 to 73) months.
      Multivariate analysis showed Contegra less than 16 mm (p<0.001; HR [hazard ratio]
      0.07), high pulmonary pressure (p<0.001; HR 4), and prior operation era (p=0.006;
      HR 0.3) as independent risk factors for Contegra replacement. The freedom from
      replacement for Contegra less than 16 mm and 16 mm or greater were 48%+/-8% and
      98%+/-2%; for presence and absence of high pulmonary pressure were 52%+/-11% and
      88%+/-3% and for era 1 and 2 were 77%+/-5% and 88%+/-4% at 60 months,
      respectively. Twenty-three of 123 surviving Contegra have a mean Doppler gradient
      greater than 20 mm Hg. Contegra less than 16 mm, smaller age group, obstructive
      arborization, and era 1 were significantly associated with higher gradients.
      While 18 (15%) surviving Contegra have moderate or more regurgitation, 88 (72%)
      have no significant gradient or regurgitation. CONCLUSIONS: Contegra grafts
      integrate well into the body. Larger Contegra show predictable function with a
      survival approaching homografts over medium term. Better case selection as one
      ascends the learning curve tends to improve survival. With easy availability and
      predictable quality, Contegra grafts continue to be a promising complement to
      homografts.

PMID- 21172513
TI  - Blood transfusion after pediatric cardiac surgery is associated with prolonged
      hospital stay.
AB  - BACKGROUND: Red blood cell transfusion is associated with morbidity and mortality
      among adults undergoing cardiac surgery. We aimed to evaluate the association of
      transfusion with morbidity among pediatric cardiac surgical patients. METHODS:
      Patients discharged after cardiac surgery in 2003 were retrospectively reviewed.
      The red blood cell volume administered during the first 48 postoperative hours
      was used to classify patients into nonexposure, low exposure (<=15 mL/kg), or
      high exposure (>15 mL/kg) groups. Cox proportional hazards modeling was used to
      evaluate the association of red blood cell exposure to length of hospital stay
      (LOS). RESULTS: Of 802 discharges, 371 patients (46.2%) required blood
      transfusion. Demographic differences between the transfusion exposure groups
      included age, weight, prematurity, and noncardiac structural abnormalities (all
      p<0.001). Distribution of Risk Adjusted Classification for Congenital Heart
      Surgery, version 1 (RACHS-1) categories, intraoperative support times, and
      postoperative Pediatric Risk of Mortality Score, Version III (PRISM-III) scores
      varied among the exposure groups (p<0.001). Median duration of mechanical
      ventilation (34 hours [0 to 493] versus 27 hours [0 to 621] versus 16 hours [0 to
      375]), incidence of infection (21 [14%] versus 29 [13%] versus 17 [4%]), and
      acute kidney injury (25 [17%] versus 29 [13%] versus 34 [8%]) were highest in the
      high transfusion exposure group when compared with the low or nontransfusion
      groups (all p<0.001). In a multivariable Cox proportional hazards model, both the
      low transfusion group (adjusted hazard ratio [HR] 0.80, 95% confidence interval
      [CI]: 0.66 to 0.97, p=0.02) and high transfusion group (adjusted HR 0.66, 95% CI:
      0.53 to 0.82, p<0.001) were associated with increased LOS. In subgroup analyses,
      both low transfusion (adjusted HR 0.81, 95% CI: 0.65 to 1.00, p=0.05) and high
      transfusion (adjusted HR 0.65, 95% CI: 0.49 to 0.87, p=0.004) in the
      biventricular group but not in the single ventricle group was associated with
      increased LOS. CONCLUSIONS: Blood transfusion is associated with prolonged
      hospitalization of children after cardiac surgery, with biventricular patients at
      highest risk for increased LOS. Future studies are necessary to explore this
      association and refine transfusion practices.

PMID- 21172514
TI  - Invited commentary.

PMID- 21172515
TI  - Comparative clinical features and immune responses after extended thymectomy for
      myasthenia gravis in patients with atrophic versus hyperplastic thymus.
AB  - BACKGROUND: Although extended thymectomy is believed to be suitable for
      myasthenia gravis (MG) patients with hyperplastic thymus, it is not clear whether
      surgical treatment is indicated for MG patients with atrophic thymus. We
      therefore assessed the clinical features and immune responses in 175 MG patients
      who underwent thymectomy between 1990 and 2004. METHODS: All patients underwent
      extended thymectomy by the transsternal approach. Clinical features, prognosis,
      and immune response after extended thymectomy were compared in patients with
      atrophic and hyperplastic thymuses. RESULTS: Of the 175 patients, 47 had atrophic
      and 128 had hyperplastic thymuses. Although the median times to complete stable
      remission of the two groups were similar (4.9 versus 4.8 years; p=0.513), the
      median time to clinical improvement was significantly longer in patients with
      atrophic thymus (3.3 versus 2.3 years; p=0.005). Patients with atrophic thymus
      showed a greater increase in ectopic thymus in the anterior mediastinal adipose
      tissue. Elevated B-cell activating factor receptor, CD19, and CD21 were observed
      in both hyperplastic and atrophic thymuses, although serum immunoglobulin G
      concentration after thymectomy increased more in patients with atrophic than in
      those with hyperplastic thymus. CONCLUSIONS: Atrophic thymus may contribute to
      the progression of MG. Patients with MG who have a atrophic thymus show similar
      postoperative prognosis as those with hyperplastic thymus, suggesting that
      surgical therapy should also be considered for the former subset.

PMID- 21172517
TI  - Invited commentary.

PMID- 21172516
TI  - Thymic neuroendocrine carcinoma and thymoma are both associated with increased
      risk of extrathymic malignancy: a 20-year review of a single institution.
AB  - BACKGROUND: Thymoma has been reported to have increased risk of extrathymic
      malignancy; thymic carcinoma, however, has not been validated of this
      association. We retrospectively assessed the incidence of additional malignancy
      among patients with thymoma and thymic carcinoma, and compared it with that of
      other solid organ cancers. METHODS: We reviewed the medical records between the
      years of 1988 and 2008 of 213 patients, including 131 with thymoma and 82 with
      thymic carcinoma. The overall incidence of additional malignancy in patients with
      thymic epithelial tumors, lung cancer, hepatocellular carcinoma, colorectal
      cancer, breast cancer, and cervical cancer between 2003 and 2008 in our
      institution was also computed. RESULTS: The incidence of extrathymic malignancy
      in patients with thymic epithelial tumors was 12.2% (16 of 131) for thymoma and
      12.2% (10 of 82) for thymic carcinoma. The overall incidence of additional
      malignancy between 2003 and 2008 was significantly higher among patients with
      thymoma than among patients with hepatocellular carcinoma, colorectal cancer,
      breast cancer, and cervical cancer (p=0.017, 0.022, 0.009, and 0.018,
      respectively). In thymic carcinoma, the likelihood of developing extrathymic
      malignancy was significantly higher among patients with neuroendocrine carcinoma
      than among patients with other thymic carcinomas (p=0.000). Extrathymic neoplasm
      did not pose a significant influence on the overall survival of patients with
      thymoma (p=0.085) and thymic carcinoma (p=0.814). CONCLUSIONS: Our data
      demonstrated the increased risk of extrathymic malignancies among patient with
      thymoma. In thymic carcinoma, this association mainly occurred in patients with
      neuroendocrine carcinoma. Actions for early detection of extrathymic malignancy
      should be considered for patients with these thymic epithelial tumors.

PMID- 21172518
TI  - Existing general population models inaccurately predict lung cancer risk in
      patients referred for surgical evaluation.
AB  - BACKGROUND: Patients undergoing resections for suspicious pulmonary lesions have
      a 9% to 55% benign rate. Validated prediction models exist to estimate the
      probability of malignancy in a general population and current practice guidelines
      recommend their use. We evaluated these models in a surgical population to
      determine the accuracy of existing models to predict benign or malignant disease.
      METHODS: We conducted a retrospective review of our thoracic surgery quality
      improvement database (2005 to 2008) to identify patients who underwent resection
      of a pulmonary lesion. Patients were stratified into subgroups based on age,
      smoking status, and fluorodeoxyglucose positron emission tomography (PET)
      results. The probability of malignancy was calculated for each patient using the
      Mayo and solitary pulmonary nodules prediction models. Receiver operating
      characteristic and calibration curves were used to measure model performance.
      RESULTS: A total of 189 patients met selection criteria; 73% were malignant.
      Patients with preoperative PET scans were divided into four subgroups based on
      age, smoking history, and nodule PET avidity. Older smokers with PET-avid lesions
      had a 90% malignancy rate. Patients with PET-nonavid lesions, PET-avid lesions
      with age less than 50 years, or never smokers of any age had a 62% malignancy
      rate. The area under the receiver operating characteristic curve for the Mayo and
      solitary pulmonary nodules models was 0.79 and 0.80, respectively; however, the
      models were poorly calibrated (p<0.001). CONCLUSIONS: Despite improvements in
      diagnostic and imaging techniques, current general population models do not
      accurately predict lung cancer among patients referred for surgical evaluation.
      Prediction models with greater accuracy are needed to identify patients with
      benign disease to reduce nontherapeutic resections.

PMID- 21172519
TI  - What is the inpatient cost of hospital complications or death after lobectomy or
      pneumonectomy?
AB  - BACKGROUND: No information exists evaluating the costs of complications or death
      after lobectomy or pneumonectomy. METHODS: We analyzed hospital costs for 294
      patients who underwent lobectomy (n=268) or pneumonectomy (n=26) from January
      2005 through September 2007. The patients were categorized into two groups on the
      basis of clinical outcomes: uncomplicated versus complications or death. A cost
      prediction model was constructed with linear regression using uncomplicated
      patients only. The model was applied to the complications or death group to
      predict the expected cost as if they had no complication. The risk-adjusted cost
      of complications or death was quantified by the difference between the observed
      cost and the expected cost. RESULTS: There were 241 patients in the uncomplicated
      group (19 pneumonectomy), and 53 patients had complications or death (7
      pneumonectomy). Length of stay was shorter for uncomplicated versus complications
      or death for both lobectomy and pneumonectomy. Pneumonectomy was costlier than
      lobectomy. Experiencing complications or death was costlier than costs associated
      with uncomplicated cases. The actual cost for uncomplicated cases was $18,380.
      The expected cost for complications or death was similar to that for
      uncomplicated cases regardless of the number of complications or death. The mean
      risk-adjusted cost of complications (95% confidence interval) increased by the
      number of complications: $11,693 ($4,430 to $18,957), $26,673 ($12,320 to
      $41,025) and $128,450 ($93,971 to $162,930) for 1, 2, and 3 complications,
      respectively. It was $49,823 ($23,187 to $76,459) for death. CONCLUSIONS:
      Patients experiencing complications or death have a similar perioperative risk
      profile as patients without complications. Hospital death or postoperative
      complications after lobectomy or pneumonectomy are economically costly.
      Decreasing inpatient death or complications would result in substantial cost-of
      care savings.

PMID- 21172520
TI  - Video-assisted thoracic surgery for bronchiectasis.
AB  - BACKGROUND: Bronchiectasis is one of the common diseases diagnosed in the world.
      No major improvement for the treatment approaches and limited efficacy promote a
      big challenge for management of this disease. Video-assisted thoracoscopic
      surgery (VATS) offers a new choice for the treatment of bronchiectasis. The
      purpose of this study was to present our experience of VATS for bronchiectasis
      and to compare this with thoracotomy in our institution. METHODS: We reviewed the
      medical records of patients who underwent VATS lobectomy and general lobectomy
      for bronchiectasis between January 2005 and December 2009. RESULTS: A total of
      279 patients underwent thoracotomy, 52 patients underwent attempted VATS
      lobectomy. Fifty-two patients from 279 patients for thoracotomy were selected and
      compared with the VATS group. Pleural adhesion was observed in 15 patients
      (28.8%) in VATS. The VATS lobectomy was converted to open thoracotomy in 7
      patients. There was no difference in the blood loss and median operative time
      between the two groups, but the patients with VATS had shorter length of stay in
      hospital (p=0.045), fewer complications (p=0.039) than those with thoracotomy.
      Forty-nine (94%) and 46 (88%) patients fully recovered after operation by VATS
      and thoracotomy, respectively. CONCLUSIONS: Video-assisted thoracoscopic
      lobectomy in localized bronchiectasis is a safe and more efficient procedure in
      selected patients with better recovery.

PMID- 21172521
TI  - Invited commentary.

PMID- 21172522
TI  - Bilateral lung transplantation offers better long-term survival, compared with
      single-lung transplantation, for younger patients with idiopathic pulmonary
      fibrosis.
AB  - BACKGROUND: Single-lung transplantation (SLT) and bilateral lung transplantation
      (BLT) are both good options for patients with end-stage lung disease secondary to
      idiopathic pulmonary fibrosis. It is, however, unclear whether BLT offers any
      survival advantage over SLT. The purpose of our study was to evaluate a large
      group of patients to determine if either SLT or BLT officered a long-term
      survival advantage for patients with IPF. METHODS: This was an Institutional
      Review Board-approved retrospective analysis of the United Network of Organ
      Sharing database from 1987 to 2008. Survival was determined using Kaplan-Meir
      estimates and the effect of laterality was determined by Cox proportional hazards
      and propensity analyses. RESULTS: Lung transplantation for idiopathic pulmonary
      fibrosis was performed in 3,860 patients (2,431 SLTs and 1429 BLTs). Multivariate
      and propensity analysis failed to show any survival advantage for BLT (hazard
      ratio = 0.90, 95% confidence interval = 0.78 to 1.0, p = 0.11). One-year
      conditional survival favored BLT (hazard ratio 0.73, 95% confidence interval 0.60
      to 0.87, p = 0.00064). Risk factors for early death included recipient age over
      57 and donor age over 36 years. CONCLUSIONS: Bilateral lung transplantation
      should be considered for younger patients with idiopathic pulmonary fibrosis and
      results may be optimized when younger donors are used.

PMID- 21172523
TI  - Extracorporeal circulatory systems as a bridge to lung transplantation at remote
      transplant centers.
AB  - BACKGROUND: Worsening of lung function in patients awaiting lung transplantation
      can lead to ventilation-refractory hypoxemia or hypercapnia and respiratory
      acidosis. This report describes the successful use of different extracorporeal
      circulatory systems as a bridge to transplantation at remote centers. METHODS:
      Between January 2003 and December 2009, we had 10 requests for implantation of
      extracorporeal circulatory systems (pumpless extracorporeal lung assist [PECLA]
      or extracorporeal membrane oxygenation [ECMO]) in patients decompensating on the
      waiting list to bridge to transplantation at three different transplant centers
      between 150 km and 570 km apart. Cannulas were inserted percutaneously with
      Seldinger's technique. RESULTS: The median patient age was 36 years (range, 24 to
      53). Three patients were supported with PECLA and 7 with ECMO. The median
      duration of support was 23 days (range, 5 to 73). Two patients were initially
      provided with ECMO and then changed to PECLA after hemodynamic stabilization in
      the face of persisting pulmonary failure. Two patients died of multiorgan failure
      on ECMO while on the waiting list. One PECLA patient was successfully weaned and
      waiting for LTx. Before transplantation, 5 patients (4 PECLA and 1 ECMO) were
      successfully weaned from mechanical ventilation, and 3 PECLA patients were
      successfully weaned from the system. Seven patients were successfully bridged and
      transplanted. Five of 7 patients were discharged from the transplant centers.
      CONCLUSIONS: This report suggests that implantation of extracorporeal circulatory
      systems is a safe method to bridge patients decompensating on the waiting list
      for transplantation. Support intervals of several weeks are possible.

PMID- 21172524
TI  - Invited commentary.

PMID- 21172525
TI  - Sternoclavicular joint infection: a comparison of two surgical approaches.
AB  - BACKGROUND: This study compares conventional open debridement with the recently
      proposed flap closure technique for sternoclavicular joint infection. METHODS:
      This is a retrospective review of patients undergoing surgery for
      sternoclavicular joint infection during the last 7 years. RESULTS: Twenty
      patients underwent 35 operations for sternoclavicular joint infection from 2002
      to 2009. The debridement and open wound procedure (10 of 20 patients, 50%)
      involved debridement of the clavicle, manubrium, and first rib and open wound
      care. The joint resection and flap closure procedure (10 of 20 patients, 50%)
      involved partial resection of the clavicle, manubrium, and first rib, with
      immediate (9 of 10) or early (1 of 10) wound closure with pectoralis major
      advancement flap. The two groups were comparable in comorbidities, duration of
      symptoms, radiologic findings, and microbiologic results. Despite an approach of
      planned reoperation for wound care, the open group had fewer mean procedures
      performed per patient (1.6+/-0.7 versus 1.9+/-1.6), owing to fewer unplanned
      procedures (0 versus 0.8 procedures/patient) than the flap group. The incidence
      of wound complications (hematoma, seroma) was lower in open patients (0 of 10
      versus 5 of 10). The median length of hospitalization was shorter in the open
      group (5.5 versus 10.5 days), but all open patients (10 of 10; 100%) required
      prolonged wound care compared with 2 of 10 (20%) in the flap group. The only
      hospital mortality occurred in the flap group. Eventual wound healing was
      satisfactory in all survivors. CONCLUSIONS: For sternoclavicular joint infection,
      a single-stage resection and muscle advancement flap leads to a higher incidence
      of complications. Debridement with open wound care provides satisfactory outcomes
      with minimal perioperative complications but requires prolonged wound care.

PMID- 21172526
TI  - Invited commentary.

PMID- 21172527
TI  - Thoracoplasty in the current practice of thoracic surgery: a single-institution
      10-year experience.
AB  - BACKGROUND: We retrospectively reviewed our recent experience with thoracoplasty
      to define its role in the context of current surgical practice. METHODS: Twenty
      six patients underwent thoracoplasty in the last 10 years with the aim of
      obliterating a residual pleural space or pulmonary cavity. Twenty-one patients
      had a postresectional empyema, 3 had a primary empyema and 2 had a cavernostomy
      performed for a pulmonary aspergilloma. A bronchopleural fistula was present in
      10 cases. Infection had been previously controlled in all cases by intercostal
      drainage, open-window thoracostomy, or cavernostomy (in 4, 20, and 2 patients,
      respectively). Twenty-two extramuscoloperiosteal thoracoplasties, 3
      thoracomyoplasties, and 1 Andrews thoracoplasty were performed. Intrathoracic
      flap transposition followed thoracoplasty in 9 cases; a second step of the
      Clagett procedure followed thoracoplasty in 2 cases. RESULTS: One patient died
      postoperatively (3.8%). Thoracoplasty alone (n=6) or combined with a procedure to
      fill the residual space (n=14) was successful in achieving complete obliteration
      of the residual space in 77% of patients (n=20). In 4 patients thoracoplasty
      alone reduced the residual cavity but filling procedures were not feasible. In 1
      patient thoracoplasty failed to obliterate the cavity and infection recurred.
      Three patients experienced chronic thoracic sequelae. CONCLUSIONS: Thoracoplasty
      remains an option for the treatment of residual pleural or pulmonary spaces (with
      or without bronchopleural fistula) once infection has been controlled, when other
      more conservative procedures are not effective or feasible. In our experience it
      was effective both when used alone in favorable conditions and when combined with
      other procedures to fill the residual cavity.

PMID- 21172528
TI  - Invited commentary.

PMID- 21172529
TI  - Endobronchial valve treatment for prolonged air leaks of the lung: a case series.
AB  - PURPOSE: An endobronchial valve developed for treatment of severe emphysema has
      characteristics favorable for bronchoscopic treatment of air leaks. We present
      the results of a consecutive case series treating complex alveolopleural fistula
      with valves. DESCRIPTION: Patients with air leaks that persisted after treatment
      gave consent and compassionate use approval was obtained. Bronchoscopy with
      balloon occlusion was used to identify the airways to be treated. IBV Valves
      (Spiration, Redmond, WA) were placed after airway measurement. EVALUATION: During
      a 15-month period, 8 valve placement procedures were performed in 7 patients and
      all had improvement in the air leak. The median duration of air leakage was 4
      weeks before and 1 day after treatment, with a mean of 4.5 days. Discharge within
      2 to 3 days of the procedure occurred in 57% of the patients. A median of 3.5
      valves (mode, 2.4) were used, and all valve removals were successful. There were
      no procedural or valve-related complications. CONCLUSIONS: Removable
      endobronchial valves appear to be a safe and effective intervention for prolonged
      air leaks.

PMID- 21172530
TI  - Peripartum cardiomyopathy with cardiogenic shock: recovery after prolactin
      inhibition and mechanical support.
AB  - After the delivery of her second child, peripartum cardiomyopathy developed in
      the 33-year-old mother, which was complicated by cardiogenic shock refractory to
      medical treatment. A left ventricular assist device was implanted, and
      bromocriptine therapy was given to facilitate myocardial recovery. Serial
      echocardiographic, hemodynamic, and exercise tests under full and partial left
      ventricular assist device support showed improvement of left ventricular
      function, such that the left ventricular assist device could be explanted 5
      months after implantation. Fourteen months after explantation, the left
      ventricular function remained stable, and the young mother is asymptomatic and
      lives a normal life.

PMID- 21172531
TI  - Open heart surgery for removal of polymethylmethacrylate after percutaneous
      vertebroplasty.
AB  - We describe a 73-year-old woman who had a right atrial-inferior vena caval
      thrombus and pulmonary thromboembolism develop after percutaneous vertebroplasty
      with methylmethacrylate. Our patient subsequently underwent open-heart surgery to
      effectively remove the bulk of the foreign material. This case illustrates the
      need for close monitoring of patients undergoing percutaneous vertebroplasty and
      emphasizes the importance of prompt diagnosis and treatment.

PMID- 21172532
TI  - Imaging and intervention of paraneoplastic effect of a right atrial myxoma on
      factor VII activity levels.
AB  - We present the case of a 64-year-old Pakistani man with right atrial myxoma,
      recently diagnosed with acquired severe factor VII (FVII) deficiency. The patient
      presented with a history of chronic hiccups and weight loss. Initial evaluation
      revealed an isolated prolonged prothrombin time, severely reduced FVII activity
      level, and a giant right atrial myxoma protruding into the right ventricle on
      computed tomographic thorax and echocardiography. After surgical resection, the
      patient maintained normal prothrombin time with increased FVII activity level in
      the immediate 24 hours postoperatively, and a dramatically high level of FVII
      activity at the 2-month follow-up. We believe that the paraneoplastic effect of
      myxoma on the FVII activity levels is previously unreported. In addition, we
      believe that hiccups as a presenting symptom for a myxoma with an atypical origin
      from the lateral wall of the right atrium has not been reported.

PMID- 21172533
TI  - Simultaneous endovascular repair of traumatic rupture of the right subclavian
      artery and thoracic aorta.
AB  - A patient with concomitant rupture of the thoracic aorta and right subclavian
      artery at its origin was managed with endovascular stents. Due to the patient's
      hypovolemic shock, kissing stents in the brachiocephalic artery were undersized,
      requiring repeat intervention with coils and cement. The technical and judgment
      aspects of this case are reviewed.

PMID- 21172534
TI  - Reversal of flow in the mammary artery to treat subclavian steal syndrome in
      conjunction with coronary bypass surgery.
AB  - Occasionally patients with multi-vessel disease present with coronary stenoses
      and subclavian steal syndrome. A novel surgical approach for the treatment of
      these vascular problems is described. The in situ left internal mammary artery
      was used to create an aortosubclavian shunt, thus restoring antegrade vertebral
      flow and vein grafts were used for coronary revascularization.

PMID- 21172535
TI  - Unusual cause of hoarseness of voice: giant pulmonary artery aneurysm.
AB  - We present an unusual case of hoarseness of the voice secondary to giant
      pulmonary artery aneurysm with special emphasis on imaging findings and also to
      illustrate preoperative and postoperative features on multi-detector computed
      tomography.

PMID- 21172536
TI  - Positron emission tomography/computed tomography for the diagnosis of
      endocarditis in patients with pulmonic stented valve/pulmonic stent.
AB  - Percutaneous pulmonic valve and pulmonic stent implantation have become a well
      established treatment for recurrent pulmonic stenosis or insufficiency in
      patients with repaired congenital heart disease. Late endocarditis is seldom
      reported, but its diagnosis might be challenging due to the limited visualization
      of the stented valve or stent by transesophageal echocardiography. We present 2
      young patients who were hospitalized for suspected endocarditis and in whom the
      diagnosis was made with the aid of positron emission tomography/computed
      tomography scan.

PMID- 21172537
TI  - Internal right ventricular band for multiple ventricular septal defects in a
      neonate undergoing arterial switch and aortic arch repair.
AB  - A neonate presented with d-transposition of the great arteries, aortic arch
      hypoplasia, aortic coarctation, and multiple ventricular septal defects. During
      the arterial switch procedure and the aortic arch repair, a fenestrated Gore-Tex
      disk (W.L. Gore & Assoc, Flagstaff, AZ) was sewn into the right ventricular
      outflow tract to restrict pulmonary blood flow. The internal right ventricular
      band successfully controlled the pulmonary blood flow, maintaining a systemic
      oxygen saturation of 88% to 92%, and allowing growth from 3.5 to 10.5 kg. At 8
      months of age, the internal band in the patient was removed, and the ventricular
      septal defects were successfully closed.

PMID- 21172538
TI  - Asymptomatic calcifying fibrous pseudotumor compressing heart cavities.
AB  - Calcifying fibrous pseudotumor is a rare benign lesion composed mostly of dense
      hyalinized colagen with multiple dystrophic or psammomatous calcifications and
      variable lymphoplasmacytic infiltrate. Children and young adults are most
      commonly affected by this tumor of uncertain pathogenesis. This is a case of an
      asymptomatic young woman with calcifying fibrous pseudotumor of the pericardium
      compressing heart cavities. Partial resection and marsupialization of the mass
      was performed.

PMID- 21172539
TI  - Cerebral air embolism as a result of inducing pneumoperitoneum after bilobectomy.
AB  - A 62-year-old man with lung cancer underwent a right lower bilobectomy of the
      lung. After resection, we insufflated air through the diaphragm into the
      peritoneal cavity, and sudden cardiac arrest developed in the patient. A large
      number of air bubbles were aspirated from the heart and great vessels, and the
      patient recovered after resuscitation. However, he remained with a left sensory
      deficit, a left homonymous hemianopia, and left hemiparesis. A brain computed
      tomographic scan revealed an acute ischemic lesion in the right parieto-occipital
      area. Our case shows that an air embolism is a possible complication of
      artificial intraoperative pneumoperitoneum after pulmonary resection.

PMID- 21172540
TI  - En bloc resection of 3 vertebra in a pancoast patient: long-term stability using
      a free vascularized fibular graft.
AB  - Vertebral involvement is no longer a contraindication for resection in superior
      sulcus tumors. We describe the reconstruction of thoracic vertebras 2 to 4 using
      a free vascularized fibular graft combined with dorsal and ventral stabilization
      using rods, screws, and hooks after resection of a superior sulcus tumor that
      invaded the thoracic spine. No complications have occurred after 7 years of
      follow-up, and the reconstruction has been durable and stable.

PMID- 21172541
TI  - Clamshell thoracotomy: a unique approach to a massive intrathoracic schwannoma.
AB  - Schwannomas (neurilemmomas) are benign tumors arising from the Schwann cells of
      the neural sheath. They are typically well-encapsulated lesions and in the chest
      they are most commonly seen within the posterior mediastinum, often originating
      along the intercostal nerves. Several operative approaches have previously been
      described for the resection of these tumors, including thoracoscopic techniques
      and posterolateral thoracotomy. We report a case of a massive schwannoma (27 cm,
      maximum diameter), unresectable by described approaches, which was successfully
      excised using a clamshell thoracotomy.

PMID- 21172542
TI  - Primary pleural epithelioid hemangioendothelioma.
AB  - Epithelioid hemangioendothelioma is a rare neoplasm of vascular endothelial
      origin. It can develop in any tissue, but it occurs primarily in the soft tissue,
      liver, and rarely in the lung. Pulmonary epithelioid hemangioendothelioma can
      present in the thorax in various manifestations. In the typical pulmonary forms,
      epithelioid hemangioendothelioma presents as either a solitary nodule, or more
      often as multiple, small nodules. Pulmonary epithelioid hemangioendothelioma
      involving the pleural space occurs in patients with disseminated disease [1, 2].
      We present a case of primary pleural epithelioid hemangioendothelioma.

PMID- 21172543
TI  - Right aortic arch with isolation of the left innominate artery arising from the
      pulmonary artery and atrial septal defect.

PMID- 21172544
TI  - Fungal osteomyelitis masquerading as a chest wall tumor.

PMID- 21172545
TI  - Two knitting needles in the thorax in a suicide attempt diagnosed on day 6 and
      treated conservatively.

PMID- 21172546
TI  - Implantable ventricular assist device exchange with focused intravascular
      deairing techniques.
AB  - As ventricular assist devices are increasingly adopted and widely implemented as
      a highly effective therapy for end-stage heart disease, extended utilization
      periods for destination therapy or bridge-to-transplantation have created the
      possibility of device failure, infection, or thrombosis, requiring challenging
      implant exchanges. A major problem in these operations is the risk of air
      embolization, particularly in a nonsternotomy approach that precludes access to
      the outflow aortic graft and to the ascending aorta. We report a minimally
      invasive, nonsternotomy HeartMate II implantable left ventricular assist device
      (LVAD) exchange, using peripheral cardiopulmonary support and a novel approach to
      continuous intravascular ascending aortic air removal.

PMID- 21172547
TI  - Anatomic and functional aortic valvuloplasty for correction of aortic valve
      prolapse in ventricular septal defect with aortic insufficiency.
AB  - We describe a new procedure of aortic valvuloplasty for aortic valve prolapse in
      ventricular septal defect with aortic insufficiency syndrome. This technique
      allows an anatomic and functional aortic valve reconstruction that prevents late
      failure of aortic valve repair and reoperation. Midterm results demonstrate the
      feasibility and durability of this new procedure.

PMID- 21172548
TI  - Sternum augmentation with bovine bone substitute in the neonate.
AB  - Delayed chest closure may be mandatory after heart surgery to treat a congenital
      disorder. Sternal closure can be challenging, even when a staged closure
      procedure has been performed. We present 2 case reports of a sternal augmentation
      technique in neonates using bovine bone substitute. Staged chest closure was
      mandatory because of cardiomediastinal disproportion in the first patient, and
      hemodynamic deterioration followed by an extracorporeal assist device in the
      second patient. We succeeded in closing the chests in these 2 neonates using this
      augmentation technique. To the best of our knowledge, these are the first 2
      reports of this type of sternum augmentation technique in neonates.

PMID- 21172549
TI  - Intrathoracic linear stapled esophagogastric anastomosis: an alternative to the
      end to end anastomosis.
AB  - Minimally invasive esophagectomy (MIE) is gradually gaining acceptance as an
      oncological sound procedure. The advantages of MIE arise from avoidance of a
      thoracotomy or laparotomy, resulting in decreased pulmonary morbidity and
      generally a faster recovery, yet not compromising the surgical benefit of
      esophagectomy in patients with cancer of the esophagus. No single technique of
      esophagectomy has proven itself superior to another from either an oncologic or
      survival perspective. The MIE is a technically demanding procedure that requires
      advanced endoscopic skills, especially when performing an intrathoracic
      anastomosis. We present an alternative intrathoracic anastomotic technique to the
      commonly performed EEA anastomosis.

PMID- 21172550
TI  - Cystoperitoneal shunt for a giant intrathoracic meningocele under local
      anesthesia.
AB  - Giant intrathoracic meningoceles are extremely rare, and the standard treatment
      for giant intrathoracic meningoceles remains controversial. We present the case
      of a patient with giant intrathoracic meningoceles associated with
      neurofibromatosis type I. Our patient had poor respiratory function because of
      the giant intrathoracic meningocele, so we performed a cystoperitoneal shunt
      under local anesthesia. We describe our cystoperitoneal shunt technique using an
      adjustable-pressure valve. This simple, minimally invasive treatment is a
      valuable alternative treatment option in patients at high operative risk,
      especially those with low respiratory function.

PMID- 21172551
TI  - Tissue-engineered cardiac constructs for cardiac repair.
AB  - Several recent basic research studies have described surgical methods for cardiac
      repair using tissue cardiomyoplasty. This review summarizes recent advances in
      cardiac repair using bioengineered tissue from the viewpoint of the cardiac
      surgeon. We conclude that the results of many basic and preclinical studies
      indicate that bioengineered tissue can be adapted to conventional surgical
      techniques. However, no clinical studies have yet proved bioengineered tissue is
      effective as a treatment for human heart failure. Today's cardiac surgeons can
      look forward to the advent of new techniques to benefit patients who respond
      poorly to existing treatment for heart failure.

PMID- 21172552
TI  - Acute myocardial infarction: an ideal platform for an effective cooperation
      between cardiologist and cardiac surgeon.

PMID- 21172553
TI  - Thrombocytopenia after freedom solo: the mystery goes on.

PMID- 21172554
TI  - Current therapeutic perspectives in peripartum cardiomyopathy.

PMID- 21172557
TI  - Transcostal sternal closure: ongoing quest for the Holy Grail.

PMID- 21172559
TI  - Effective median sternotomy closure after open heart operations.

PMID- 21172560
TI  - Is remote ischemic preconditioning triggered by intermittent claudication
      secondary to peripheral arterial disease responsible for preventing early
      mortality after coronary artery bypass surgery?

PMID- 21172561
TI  - Extrapleural intrathoracic pacemaker for congenital heart block.

PMID- 21172562
TI  - Stereotactic lung radiotherapy: do we need fiducial markers?

PMID- 21172564
TI  - Tumor-associated glycoprotein (TAG-72) is a natural ligand for the C-type lectin
      like domain that induces anti-inflammatory orientation of early pregnancy
      decidual CD1a+ dendritic cells.
AB  - Tumor-associated glycoprotein-72 (TAG-72) is physiologically present in secretory
      phase endometrium, but its presence and possible immunological role in early
      normal human pregnancy decidua has not received attention. The double labeling of
      paraffin-embedded early pregnancy decidua sections using B-72.4 anti-TAG-72 mAb
      and MNF 116 anti-cytokeratin mAb revealed the absence of TAG-72 in uterine
      decidua of normal and pathological pregnancies (non-embryonic pregnancy and
      missed abortion) at the implantation sites, although it was present in epithelial
      cells at and away from the tubal implantation site of an ectopic pregnancy. TAG
      72 binds and internalizes by reacting with the mannose receptor (MR-CD206) or
      with DC-specific ICAM reacting non-integrin (DC-SIGN-CD209) on decidual CD1a+
      cells. Decidual CD1a+ cells stimulated with TAG-72 decreased CD83 expression and
      diminished IL-15 and IFN-gamma intracellular production. TAG-72-treated CD1a+
      cells decreased IFN-gamma production in syngenic decidual and allogenic cord
      blood T cells even in the presence of lipopolysaccharide. TAG-72- and
      lipopolysaccharide-pre-treated CD1a+ cells significantly increased IL-4
      expression in allogenic cord blood T cells. TAG-72 increased allogenic cord blood
      T cell proliferation, mediated by decidual CD1a+ cells, compared with its effect
      on the proliferation of syngenic decidual T cells. All these data emphasize the
      anti-inflammatory properties of TAG-72-treated decidual CD1a+ cells in terms of
      their interaction with T cells. Thus, the absence of TAG-72 at the maternal-fetal
      interface during early pregnancy could lead to a mild pro-inflammatory response
      that may be beneficial for pregnancy success and trophoblast growth control.

PMID- 21172565
TI  - Special issue "Bioactive lipids, nutrition and health".

PMID- 21172566
TI  - Psychiatry for the neurologist. Preface.

PMID- 21172567
TI  - Functional neurologic symptoms: assessment and management.
AB  - Neurologic symptoms such as weakness or abnormal movements that are inconsistent
      and incongruent with neurologic disease can be described as functional,
      psychogenic, nonorganic, conversion, or dissociative symptoms. These symptoms
      often represent a clinical dilemma and a challenge for the clinician. This
      article provides practical advice on making an accurate diagnosis, options for
      explaining the diagnosis to the patient, and considering further treatment.

PMID- 21172568
TI  - Neuropathic pain: mind-body considerations.
AB  - Emerging research in neuroscience is bridging the gap between mind and body.
      Thought is brain based and influences brain function. The continuum and
      bidirectionality of mind and body, thought and brain, emotions and physiology
      forms the basis of understanding neuropathic pain, a neuropsychiatric condition
      with myriad clinical manifestations.

PMID- 21172569
TI  - Traumatic brain injury and its neurobehavioral sequelae.
AB  - The neurobehavioral sequelae of TBI consist of a spectrum of somatic, neurologic,
      and psychiatric symptoms. The challenge for clinicians lies in understanding the
      interface of the various symptoms and how they interrelate with other entities.
      Specifically, the challenge is differentiating post-TBI-related symptoms from
      preexisting or de novo psychiatric, neurologic, and/or systemic disorders. A
      comprehensive evaluation and a multidisciplinary approach to evaluating patients
      are essential to be able to develop the differential diagnosis needed to design a
      management plan that maximizes recovery.

PMID- 21172571
TI  - Headaches: psychiatric aspects.
AB  - Headache, and in particular, migraine, is often associated with comorbid
      psychiatric illness. The complex relationships between these disorders are slowly
      becoming understood. Successful management requires an integrated approach of
      neurologic and psychiatric management.

PMID- 21172572
TI  - White matter: beyond focal disconnection.
AB  - The complex phenomenology of white matter dementia and many neuropsychiatric
      disorders implies that they originate from involvement of distributed neural
      networks, and white matter neuropathology is increasingly implicated in the
      pathogenesis of these network disconnection syndromes. White matter disorders
      produce functional asynchrony of interdependent cerebral regions subserving
      normal cognitive and emotional functions. Accumulating evidence suggests that
      white matter dementia primarily reflects disturbed frontal systems connectivity,
      whereas disruption of frontal and temporal lobe systems is implicated in the
      pathogenesis of neuropsychiatric disorders. Continued study of normal and
      abnormal white matter promises to help resolve challenging problems in behavioral
      neurology and neuropsychiatry.

PMID- 21172570
TI  - Neuropsychiatry of aggression.
AB  - Aggression is a serious medical problem that can place both the patient and the
      health care provider at risk. Aggression can result from medical, neurologic,
      and/or psychiatric disorders. A comprehensive patient evaluation is needed.
      Treatment options include pharmacotherapy as well as nonpharmacologic
      interventions, both of which need to be individualized to the patient.

PMID- 21172573
TI  - Affective symptoms in early-onset dementia.
AB  - The phenotypic expression of neuropsychological deficits can have very different
      genotypic etiologies. Understanding the causes of various neuropsychological
      deficits is tantamount in developing the appropriate treatments. The literature
      on mood disorders as a risk factor for dementia is reviewed as well as common
      neuropsychological patterns in dementia and mood disorders. A brief discussion on
      chronic traumatic encephalopathy is provided.

PMID- 21172574
TI  - The assessment of decisional capacity.
AB  - The physician must explain the treatment or procedure in detail including risks,
      benefits, and alternative options; the patient's choice must be voluntary; the
      patient must demonstrate his or her ability to understand the risks and benefits
      of their choice; and the patient must be able to manipulate information in a
      logical way. These criteria must be met in order for the process of informed
      consent to be valid.

PMID- 21172577
TI  - Ictal panic and interictal panic attacks: diagnostic and therapeutic principles.
AB  - Ictal and postictal panic and interictal and primary panic attacks share common
      symptoms but differ with respect to duration and association with other symptoms.
      A careful history is often sufficient to distinguish these events. When
      necessary, electroencephalography and neuroimaging studies, estimation of
      prolactin levels can be a helpful tool in establishing an accurate diagnosis.

PMID- 21172576
TI  - Differentiating frontal lobe epilepsy from psychogenic nonepileptic seizures.
AB  - Patients with psychogenic nonepileptic seizures (PNES) remain one of the most
      challenging patient populations. The misdiagnosis of PNES is costly to patients,
      the health care system, and to society. The first step in treatment is proper
      diagnosis. Video electroencephalography remains the gold standard for PNES
      diagnosis. Differentiating frontal lobe epilepsy (FLE) from PNES can be
      difficult; however, clinical findings and laboratory advances are emerging that
      more clearly establish the diagnosis of PNES. This article provides clues to
      differentiating FLE from PNES so that neurologists and mental health providers
      are better equipped to offer treatments for PNES.

PMID- 21172578
TI  - Diagnosis and treatment of major depressive disorder.
AB  - Major depressive disorder is a common illness, particularly in patients with
      medical and neurologic conditions. This article summarizes current data on the
      epidemiology, diagnosis, and treatment of major depression, with special emphasis
      on the diagnosis and treatment of depression in medical and neurologic patients.
      We reviewed the role of pharmacotherapies, psychotherapies, somatic treatments,
      and alternative remedies and we included practical advice for clinician regarding
      the timing and sequence of these treatments, the role of standardized depression
      scales, and the criteria for referrals to specialty consultants.

PMID- 21172575
TI  - Movement disorders induced by antipsychotic drugs: implications of the CATIE
      schizophrenia trial.
AB  - Drug-induced movement disorders have dramatically declined with the widespread
      use of second-generation antipsychotics, but remain important in clinical
      practice and for understanding antipsychotic pharmacology. The diagnosis and
      management of dystonia, parkinsonism, akathisia, catatonia, neuroleptic malignant
      syndrome, and tardive dyskinesia are reviewed in relation to the decreased
      liability of the second-generation antipsychotics contrasted with evidence from
      the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)
      Schizophrenia Trial. Data from the CATIE trial imply that advantages of second
      generation antipsychotics in significantly reducing extrapyramidal side effects
      compared with haloperidol may be diminished when compared with modest doses of
      lower-potency first-generation drugs.

PMID- 21172580
TI  - Emerging national trends in the management and outcomes of lower extremity
      peripheral arterial disease.
AB  - BACKGROUND: In this study, we sought to analyze emerging national trends in the
      treatment of lower extremity peripheral arterial disease and associated outcomes.
      METHODS: The Nationwide Inpatient Sample was queried between 2001 and 2007.
      Patients diagnosed with lower extremity atherosclerosis were selected by using
      the International Classification of Diseases, 9th Revision codes 440.20-440.24,
      resulting in an average of 307,000 annual hospitalizations. Within this group, we
      determined the annual number of lower extremity bypasses, endovascular
      interventions, and major and/or minor amputations (below-the- and/or above-the
      knee amputation versus toe and/or foot amputation). Chi-square analysis was
      performed on discharge-weighted data to compare two periods (2001-2003 and 2004
      2007) to determine changes in management and differences in outcome. Multivariate
      logistic regression was used to identify predictors of amputation. RESULTS:
      Comparing the two periods, it was found that the average annual number of
      endovascular interventions increased by 78% (37,692 vs. 67,248, p < 0.001), and
      open lower extremity bypasses decreased by 20% (68,326 vs. 54,348, p < 0.001).
      Annually, the total number of interventions increased by 15% (106,018 vs.
      121,596, p < 0.001), whereas the number of total amputations (59,693 vs. 50,254,
      p < 0.001), major amputations (39,543 vs. 31,043, p < 0.001), and minor
      amputations (20,150 vs. 19,211, p < 0.001) performed all significantly decreased.
      Diabetes was the leading predictor of amputation, especially those involving the
      toe and forefoot. After adjusting for age and comorbidities, African Americans
      were found to have a 2.4 times odds of amputation as compared with Caucasians,
      whereas those with Medicare or Medicaid had a 1.5 times odds as compared with
      those having private insurance or Health Maintenance Organization. CONCLUSIONS:
      Between the periods examined, we observed that the treatment of lower extremity
      peripheral arterial disease has evolved with increased use of lesser invasive
      endovascular techniques and fewer open lower extremity bypasses. These trends are
      associated with fewer major lower extremity amputations. Significant
      socioeconomic disparities persist in amputation rates, with racial minorities and
      those with Medicare or Medicaid having higher odds of amputation.

PMID- 21172581
TI  - Laser saphenous ablations in more than 1,000 limbs with long-term duplex
      examination follow-up.
AB  - BACKGROUND: The goal of this study was to evaluate the duplex results of
      endovenous laser ablation in the treatment of incompetent great saphenous veins
      (GSV) and small saphenous veins (SSV) with at least 1-year follow-up. METHODS: A
      retrospective registry was entered by 11 centers from Europe and America,
      organized by the International Endovenous Laser Working Group. Data concerning
      1,020 limbs in patients with incompetence of the GSV and/or SSV, treated with the
      Endovenous Laser Ablation (EVLA) procedure, were collected. EVLA failures were
      defined on duplex imaging as reflux confined to the saphenofemoral or
      saphenopopliteal junction, reflux confined to the main saphenous trunk, or reflux
      of both junction and main trunk (totally patent saphenous vein) were analyzed at
      one or more years postoperatively. RESULTS: The mean age of patients was 54 +/- 5
      years (range: 18-91 years). The average body mass index was 25. There was a
      paucity of severe complications: One case of third-degree skin burn, six patients
      with postsurgical deep vein thrombosis (0.6%), and 27 cases of sensory nerve
      damage (2.7%). At 1-year, the rate of complete occlusion of the saphenous trunk
      was 93.1%. There were 79 cases of treatment failures as evidenced by duplex: 22
      isolated junction failures (2.2%), 44 isolated trunk failures (4.4%), and 13
      totally patent veins (1.3%). Two-year duplex results were reported for 329 limbs
      with the identification of 19 new cases of failure. No new cases of failure were
      reported at 3-year follow-up of 130 limbs. Cumulative failure rates estimated by
      Kaplan-Meier analysis were 7.7% at 1-year and 13.1% at 2- and 3-year follow-up.
      CONCLUSIONS: On the basis of a duplex scan performed at least 1-year post
      treatment, this multicenter registry confirms the safety and efficacy of the EVLA
      procedure in the treatment of GSV and SSV reflux. Considering the continued
      failure rate documented in the present study, an annual follow-up by duplex is
      recommended to 2 years after EVLA.

PMID- 21172582
TI  - The effect of percutaneous intervention on wound healing in patients with mixed
      arterial venous disease.
AB  - BACKGROUND: Open venous ulcers in patients with combined arterial and venous
      insufficiency are notoriously hard to treat. Patients with an ankle-brachial
      index (ABI) of 0.5-0.8 have been shown to heal poorly. Because adequate
      compression therapy is contraindicated in patients with an ABI of <0.7, we
      decided to undertake an aggressive approach of percutaneous revascularization for
      these patients. METHODS: A total of 27 patients with clinical and duplex scan
      evidence of chronic venous insufficiency, active leg ulcers, and impaired
      arterial perfusion (ABI: <0.7) were treated using a protocol that required
      performing percutaneous revascularization before ambulatory compression therapy.
      The patients were followed at 2-week intervals (average) before and after
      revascularization. Wound measurements and time to complete closure were also
      recorded. RESULTS: The results of the patients were compared with their own
      previous wound healing trajectories. Additionally, their healing rate was
      compared with previously published rates of impaired arterial perfusion venous
      wound closure; 25% closure at 10 weeks, 50% at 19 weeks. At enrollment, the
      average ABI and wound sizes were 0.56 and 12 cm(2), respectively. On average, the
      wounds had remained open for 17 weeks. After the intervention, the average ABI
      was 0.97, average time taken to complete closure was 10 weeks, closure rate at 10
      weeks was 75%, and absolute closure rate was 100%. CONCLUSION: Although previous
      studies have shown that closure of mixed arterial venous ulcers occur without
      arterial intervention, attaining a near normal ABI allows for timelier wound
      closure. Therefore, we advocate an aggressive approach of percutaneous
      revascularization in this population.

PMID- 21172583
TI  - Single center experience with modified eversion carotid endarterectomy.
AB  - BACKGROUND: Transaortic endarterectomy is a well-described technique for surgical
      revascularization of orificial atherosclerotic renovascular disease. Adopting
      this technique to carotid endarterectomy (CEA), modified eversion carotid
      endarterectomy (MECE), uses a traditional longitudinal arteriotomy that is
      confined to the bulb. This obviates the need for patch closure, simplifies the
      procedure, and permits easy conversion to traditional patch closure carotid
      endarterectomy (PCEA) for technical defects. We compared the safety and efficacy
      of this technique with PCEA. METHODS: Three vascular surgeons performed 223 CEAs
      between July 2004 and December 2008 at a tertiary teaching hospital. Outcomes
      measured included perioperative stroke rate, morbidity rate, mortality rate, and
      late restenosis. The incidence of moderate (60-79%) and severe (>=80%) restenosis
      was examined at <6 weeks, 1 year, and >=2 years after operation. All patients
      included in this study underwent follow-up for >12 months. Data were analyzed
      with Student's t-test (p < 0.05 = significant). RESULTS: CEA was performed for
      symptomatic disease in 40.4% (90/223) of patients. One surgeon performed MECE in
      73.3% (99/135) of his patients during this period; the remaining patients (n =
      124) underwent traditional PCEA. Intraoperative completion duplex ultrasound was
      performed for all patients. In 5.1% (5/99) of the patients, MECE was converted to
      PCEA for residual flaps. Intraoperative carotid cross-clamping time was
      significantly shorter in the MECE group (29.2 minutes vs. 52.2 minutes, p <
      0.05). For patients in the PCEA group, the overall mortality rate was 1.8%
      (4/223), and perioperative stroke rate was 1.4% (3/223). Overall morbidity was
      7.2%, which was similar between the two groups. Late restenosis rate on duplex
      scan was 7.1% (1.0% severe stenosis), early occlusion occurred in one patient
      with PCEA, and the reintervention rate was 1.0% (2/196). The incidence of late
      restenosis was similar between the MECE and PCEA group (8.4% vs. 6.2%, p = 0.55).
      Mean follow-up was 26.3 months for the MECE group and 29.4 months for the PCEA
      group. CONCLUSIONS: MECE is a safer alternative to conventional endarterectomy
      with a restenosis rate comparable with PCEA, offers the potential advantage of
      shorter clamping time, and obviates the need for patch closure.

PMID- 21172584
TI  - Evaluating outcomes of endoleak discrepancies between computed tomography scan
      and ultrasound imaging after endovascular abdominal aneurysm repair.
AB  - BACKGROUND: Endovascular repair for abdominal aortic aneurysm (EVAR) requires
      regular surveillance to ensure long-term durability. To understand the clinical
      consequence of discrepancies in endoleak detection between computed tomographic
      angiography (CTA) and duplex ultrasound (DUS) imaging, this study evaluated
      patients who underwent EVAR. The aim of the present study was to determine
      whether these discrepancies affected the long-term outcome after EVAR, and
      whether DUS predicted the need for re-intervention on the basis of other markers
      despite missing endoleaks. METHODS: A review of the prospectively maintained
      database was completed to capture all EVAR procedures performed between October
      1999 and June 2009. Patients were routinely evaluated with computed tomography
      (CT) and DUS imaging within 30 days after the procedure and intermittently at 6
      12 month intervals after treatment. DUS imaging was evaluated with attention
      toward maximum aneurysm diameter, presence of an endoleak, and compared with
      findings on simultaneous contrast CT imaging. RESULTS: The database and patient
      records identified 1,062 EVARs in 992 patients who underwent 3,120 imaging
      encounters through the surveillance protocol. Of these 3,120 encounters, 610 had
      both CT scan and ultrasound at the same visit. Contrast material was not used in
      49 CT scans, leaving 561 encounters for comparing contrast CT imaging with DUS
      results. CT and DUS detection of endoleaks correlated in 442 encounters (78.8%).
      Discrepancies occurred in 119 encounters (21.2%) as follows: CT scan only
      endoleak in 17.8% (N = 100; type I = 6, type II = 91, and type III = 3) and DUS
      only endoleak in 3.4% (N = 19; type II = 19) encounters. Of these 119 encounters,
      99 (17.6%) did not require secondary interventions. Eventually, 15 patients
      required intervention after 20 discrepancy encounters (3.6%): 11 patients
      continued with the surveillance protocol through CT or DUS imaging, whereas four
      were observed by CT imaging only. Considering these 11 patients, DUS eventually
      detected an endoleak on subsequent visits in five patients, DUS identified an
      increase in aneurysm diameter in four patients, and DUS never identified the type
      II endoleaks in two patients. When the endoleak raised concern or the aneurysm
      enlarged, we undertook 19 secondary interventions in these 15 patients: vessel
      embolization (N = 8), iliac extenders (N = 5), graft relining (N = 3), graft
      explants (N = 2), and proximal cuff (N = 1). Although three ruptures occurred in
      our entire treatment experience, no ruptures occurred in patients who maintained
      the prescribed surveillance protocol. CONCLUSION: Surveillance after EVAR is
      necessary because secondary interventions are sometimes required. Although DUS
      has lower sensitivity in detecting endoleaks, comparison with CT findings can
      identify the appropriate patients for DUS surveillance only. Even considering the
      discrepancies between CT imaging and DUS, repeated DUS surveillance might
      identify an unstable aneurysm that requires further intervention. Although DUS
      has not been established as an exclusive surveillance tool, it can be used to
      effectively monitor patients after EVAR with reduced need for CT imaging.

PMID- 21172585
TI  - Long-term results of endoscopic versus open saphenous vein harvest for lower
      extremity bypass.
AB  - BACKGROUND: Endoscopic saphenous vein harvest (EVH) has been shown to lower wound
      infection rates and cost compared with conventional harvest, although long-term
      patency data are lacking. A small series of studies has recently suggested that
      patency is inferior to conventionally harvested vein technique, and we thus
      sought to explore this question by reviewing our cumulative experience with this
      technique. METHODS: The short- and long-term outcomes of all lower extremity
      bypasses (LEBPs) using saphenous vein at one institution over a period of 8.5
      years were retrospectively reviewed. RESULTS: A total of 363 patients averaging
      67 +/- 24 to 100 years of age had undergone LEBP and had charts available for
      review. Of these 363 patients, 170 underwent EVH (90% using a noninsufflation
      technique) and 193 conventional (by means of continuous or skip incisions); 48%
      of patients reported tissue loss and no differences in indication for surgery
      were noted between groups. Mean follow-up was 35.1 (range: <1-105) months.
      Primary patency rates were worse in the EVH group as compared with conventional
      at six (63.3% +/- 4.0% vs. 77.3% +/- 3.3%), 12 (50.4% +/- 4.2% vs. 73.7% +/-
      3.6%), and 36 (42.2% +/- 4.5% vs. 59.1% +/- 4.9%) months (all p < 0.001),
      although these differences were largely limited to patients with limb-threat and
      diabetes. However, limb salvage and survival, were identical between groups.
      Contrary to previous experience, there were no differences in length of stay or
      wound complication rates. CONCLUSIONS: The overall results of this study show an
      inferior long-term patency rate for endoscopically harvested saphenous vein after
      LEBP in our series as a whole, and do not confirm the short-term benefit
      previously shown in a selected cohort. These differences were, however, minimal
      or absent in patients with claudication or absence of diabetes, and EVH may
      continue to play a role in these cases.

PMID- 21172586
TI  - Surgical management of hemodialysis-related central venous occlusive disease: a
      treatment algorithm.
AB  - BACKGROUND: Creation and preservation of dialysis access in patients with central
      venous occlusive disease (CVOD) is a complex problem. The surgical approach and
      decision-making process remains poorly defined. We evaluated our experience in
      the surgical management of hemodialysis-related CVOD. Surgical technique,
      demographics, complications, reinterventions, access function rates, and factors
      influencing morbidity and mortality were examined. METHODS: From January 2006 to
      May 2010, we performed a total of 1,703 dialysis access-related procedures, 1,021
      arteriovenous fistulas (AVFs), 335 arteriovenous grafts (AVGs), and 314 access
      revisions including endovascular salvage procedures. Seventeen patients (10 women
      [58%] with a mean age of 44 +/- 27 years) with CVOD who were not suitable for
      peritoneal dialysis or kidney transplant underwent 20 complex vascular access
      procedures. The indications were need for access creation in 14 cases (70%) and
      preservation in the remaining 6 (30%). Polytetrafluoroethylene (PTFE) was used
      for all surgical bypass grafts (BPG). All patients had previously undergone
      multiple access surgeries and had failed percutaneous interventions for CVOD.
      RESULTS: The surgical planning centered on finding venous outflow for an
      arteriovenous (AV) access; central venous reconstructions were necessary in 10
      (50%) cases (seven [35%] in the thoracic central venous system and three [15%] in
      infradiaphragmatic vessels) and extracavitary venous BPG in two (10%) cases. Non
      venous access options included axillary arterial-arterial chest wall BPG in five
      (25%) cases and brachial artery to right atrium BPG in three (15%). Technical
      success was achieved in all cases (100%). Mean follow-up was 14.1 months, both
      BPG and AV access patency rates were 66% at 6 months and overall average AV
      access function time was 9.2 months. Of these, 85% of patients were discharged
      home and following 19 (95%) cases they returned or improved their baseline
      functional status. One death occurred from multiorgan failure during the 30-day
      postoperative period. Four additional patients died within 3 years of the
      procedure secondary to nonsurgical-related comorbidities. CONCLUSION: The need
      for complex vascular accesses will continue as the number of patients with end
      stage renal disease increases. CVOD is an access surgical challenge and with this
      article we propose a decision-making algorithm.

PMID- 21172587
TI  - Long-term outcomes of Palmaz stent placement for intraoperative type Ia endoleak
      during endovascular aneurysm repair.
AB  - BACKGROUND: Perioperative proximal endoleaks during endovascular aneurysm repair
      potentiate graft migration, aneurysm sac expansion, and stent-graft failure.
      Adjunctive placement of a Palmaz stent at the proximal landing zone can improve
      proximal seal and eliminate perigraft flow; however, the long-term sequelae
      associated with this maneuver are unknown. We sought to evaluate the effect of
      Palmaz stent placement for type Ia endoleaks on delayed endoleak formation, graft
      migration, and aneurysm expansion. METHODS: A retrospective cohort review of a
      prospectively maintained database was performed. Between 2000 and 2005, all
      consecutive patients who had undergone infrarenal endovascular aneurysm repair
      were evaluated for a type I endoleak that was treated with Palmaz stent
      placement. Fenestrated, juxtarenal, and investigational devices were excluded
      from the analysis. Postoperative and follow-up axial imaging were analyzed for
      the following three primary endpoints: type I endoleak formation, stent-graft
      migration, and aneurysm sac expansion. In addition, a paired analysis was
      performed comparing suprarenal aortic diameters, infrarenal aortic neck
      diameters, aortic neck lengths, and proximal seal zones. RESULTS: In all, 36
      consecutive patients were identified with intraoperative type I endoleaks that
      were treated with Palmaz stenting. Five patients with ruptured abdominal aortic
      aneurysms died before discharge; the remaining 31 patients comprised the cohort
      for analysis. During a median follow-up period of 53 months (interquartile range:
      14-91 months), no type I endoleak developed after Palmaz stent placement. Despite
      patients experiencing shortening of aortic neck length (26%) and loss of the
      proximal seal zone (35%), no stent-graft migration was seen in this population.
      Continued aortic degeneration accounted for proximal seal zone loss. At a
      distance 15 mm below the lowest renal artery, the mean aortic diameter increased
      by 3.2 mm (95% confidence interval: 0.4-6, p < 0.5), and 63% of patients
      demonstrated an increase of >10%. Mean aortic sac regression was 5.8 mm (95%
      confidence interval: 0.5-11.0, p < 0.05). Overall, at the final follow-up
      evaluation, aortic sac regression was found to have occurred in 55% of patients,
      aortic sac increased up to 10% in 20% of the patients, and by more than 10% in
      25% of the patients. CONCLUSIONS: Proximal neck reinforcement with a Palmaz stent
      serves as an effective endovascular adjunct to treat intraoperative type I
      endoleaks, and has a very high technical success rate. Most importantly, it has a
      clinical effect on delayed type I endoleak formation and stent-graft migration.

PMID- 21172588
TI  - Full metal jacket stenting of the superficial femoral artery: a retrospective
      review.
AB  - BACKGROUND: The technique of long segment stenting of the superficial femoral
      artery (SFA) has been associated with poorer short- and long-term results. The
      full metal jacket (FMJ) stenting is typically described as long segment
      continuous stenting of a vessel segment. Initially, this technique was described
      in percutaneous coronary interventions. However, until recently, FMJ of the SFA
      has not been studied. We examined our experience with FMJ of the SFA to evaluate
      the outcomes and the safety of this technique. METHODS: Retrospective data were
      gathered for peripheral angioplasties and stenting for the period between January
      2005 and December 2008. The cases involving FMJ stenting of the SFA were
      identified by angiographic findings and the operative dictations providing the
      stent data. Selective FMJ stenting of the SFA was performed for the residual
      stenosis after balloon angioplasty of the SFA because of either dissection or
      significant recoil. The cases with concomitant iliac artery angioplasty and/or
      stenting were excluded from the data set for analysis. The variables for the
      evaluation were primary patency rate, mortality rate, and limb salvage rate,
      which were stratified on the basis of the risk factors. RESULTS: A total of 63
      cases involving FMJ stenting of the SFA were identified from the database of 707
      patients who had peripheral endovascular interventions between January 2005 and
      December 2008. Average age of the patients was 70 years (range: 52-104 years, SD:
      10.1 years). There were no transatlantic inter-society consensus (TASC) A
      lesions, 11% (7/63) of the lesions were TASC B, 68% (43/63) were TASC C, and 21%
      (13/63) were TASC D. The median primary patency rate was 9 months (95% CI: 5.06
      12.94). The mortality rate was 4% at 6-month follow-up. The limb salvage rate was
      85.7%. In all, 65% (41/63) of the patients were claudicants, whereas 23% (15/63)
      had intervention for some form of tissue loss (ischemic ulcer, gangrene).
      Associated infrapopliteal intervention was performed in 15.9% of the patients.
      Average creatinine level was 1.67 (range: 0.7-10.9, SD: 2.03) and 49% (31/63) of
      the patients had diabetes. The average 6-month patency rate was 55% (SD: 0.5).
      Multivariate logistic regression analysis showed that diabetes (OR: 0.33, p =
      0.044, 95% CI: 0.11-0.97) and a creatinine level of >=1.6 (OR: 0.16, p = 0.038,
      95% CI: 0.03-0.9) were the independent risk factors for loss of patency in <6
      months. CONCLUSION: Our experience suggests promising results for the technique
      of FMJ of the SFA and also that further examination of the technique is
      warranted.

PMID- 21172589
TI  - Rifampin-bonded vascular grafts and postoperative infections.
AB  - Postoperative wound and graft infections remain a major challenge for vascular
      surgeons. The bonding of antimicrobial substances on the graft material has been
      considered for many years, but the demonstration of safety and efficacy of these
      techniques is far from evident. Among the different proposed options, bonding of
      rifampin to the grafts has been the most evaluated technique, both experimentally
      and clinically. The objective of this review was to present and analyze the
      available data on rifampin-bonding and the possible evolutions of this technique
      to improve the resistance of vascular prostheses.

PMID- 21172590
TI  - Results of open pararenal abdominal aortic aneurysm repair: Tabular review of the
      literature.
AB  - Open surgical repair of complex abdominal aortic aneurysms requires more
      extensive dissection and aortic clamping above the renal or mesenteric arteries.
      Although results of open surgical series have shown variation, morbidity and
      mortality is higher compared with infrarenal aortic aneurysm repair. Potential
      complications include renal insufficiency, mesenteric ischemia, multisystem organ
      failure, and death. Although endovascular treatment with fenestrated and branched
      endografts might potentially decrease the risk of complications and mortality,
      its role is not yet defined and the technology is not widely available. Issues
      related to durability of the procedure and secondary interventions might limit
      its application to patients with higher risk or those with hostile anatomy. This
      article summarizes the clinical results of open surgical repair of pararenal
      abdominal aortic aneurysms to provide a benchmark for comparison with results of
      endovascular treatment, using fenestrated and branched techniques.

PMID- 21172593
TI  - The emergence of a sub-specialty: the interventional echocardiographer.

PMID- 21172594
TI  - American Society of Echocardiography recommendations for quality echocardiography
      laboratory operations.

PMID- 21172595
TI  - Improving quality in echocardiography laboratories.

PMID- 21172597
TI  - Left ventricular outflow tract obstruction in hypertrophic cardiomyopathy: do we
      need to stand to be counted.

PMID- 21172596
TI  - Predictors of coronary artery visualization in Kawasaki disease.
AB  - BACKGROUND: Echocardiography is the imaging modality of choice for the evaluation
      of coronary artery (CA) abnormalities in Kawasaki disease. Small series have
      established high specificity and sensitivity for detecting abnormalities, yet
      visualization rates of individual CA segments and factors associated with success
      are unknown. METHODS: In the Pediatric Heart Network's randomized trial of
      primary steroid treatment for Kawasaki disease, echocardiograms were interpreted
      locally and by a core laboratory. Univariate and multivariate predictors of CA
      visualization by the local lab as determined by the core lab were explored, and
      agreement of CA size measured locally and by the core lab was assessed. RESULTS:
      A total of 589 echocardiograms from 199 patients were obtained over 27 months.
      Visualization rates for the left main, proximal and distal left anterior
      descending, and proximal right CAs ranged from 91% to 98% but were lower for the
      distal right (65%), circumflex (86%), and posterior descending (54%) CAs. For the
      distal right and circumflex CAs, visualization rates improved over the course of
      the study (P<.05). In multivariate analysis, local center, CA segment, and time
      from study start to echocardiography were independent predictors of visualization
      (all P values<.001). For segments for which visualization rates varied by center,
      higher percentage visualization was associated with larger center volume
      (P=.001). Routine sedation use was also associated with higher visualization
      rates. CONCLUSIONS: Successful CA visualization in Kawasaki disease is associated
      with the segment being evaluated and is influenced by center volume and sedation
      use. Increased visualization rates over time suggest a learning curve and
      underscore the value of core lab oversight in pediatric multicenter trials.

PMID- 21172598
TI  - Occurrence of atrial fibrillation during dobutamine stress echocardiography:
      incidence, risk factors, and outcomes.
AB  - BACKGROUND: The reported incidence of atrial fibrillation (AF) occurring during
      dobutamine stress echocardiography (DSE) ranges from 0.5% to 4%. The aim of this
      study was to characterize the incidence, risk factors, and outcomes of AF
      precipitated during DSE. METHODS: The clinical and echocardiographic data of
      consecutive patients over a 50-month period who were in sinus rhythm and
      underwent DSE were retrospectively reviewed. RESULTS: A total of 11,806
      consecutive patients underwent DSE and met all inclusion criteria. AF developed
      during DSE in 122 patients (1%), 71 of whom had histories of AF. The duration of
      AF was <1 hour in 74 patients (61%) and<24 hours in 117 patients (96%). Of the 47
      patients who were still in AF when dismissed from the echocardiography
      laboratory, 21 had outpatient follow-up within 24 hours, eight were already
      inpatients, and 18 were triaged to the emergency department or hospital.
      Spontaneous cardioversion occurred in 114 patients (93%). There were no reported
      complications. The clinical characteristic most strongly associated with the
      development of AF during DSE was a history of AF (odds ratio, 18.4 if no history
      of congestive heart failure; P<.001). The presence or extent of stress-induced
      myocardial ischemia was not predictive of the development of AF. CONCLUSIONS: AF
      is an infrequent complication of DSE. Most patients return to sinus rhythm
      spontaneously within 1 hour. Patients with persistent AF can be safely dismissed
      from the echocardiography laboratory to have outpatient follow-up within 24 hours
      unless they have suboptimal heart rate control, hypotension, significant
      symptoms, or markedly abnormal findings on DSE.

PMID- 21172600
TI  - Ongoing innovation in meta-analysis.

PMID- 21172601
TI  - The quality of safety reporting in trials is still suboptimal: survey of major
      general medical journals.
AB  - OBJECTIVE: To evaluate whether the quality of reporting harms improved after the
      publication of the Extension of the Consolidated Standards of Reporting Trials
      (CONSORT) statement and predictors that influence the safety reporting in
      randomized controlled trials (RCTs) STUDY DESIGN AND SETTING: Systematic survey
      of published RCTs assessing drugs. In MEDLINE, we identified 228 RCTs published
      in Annals of Internal Medicine, British Medical Journal, Journal of American
      Medical Association, The Lancet, and The New England Journal of Medicine in 2003
      and 2006. RESULTS: The reporting of harms have improved over time both in quality
      and extent of space. However, the mean score as an overall measure of adequacy in
      reporting harms was 0.58 in 2003 and increased to 0.67 in 2006, indicating a
      moderate safety reporting. Safety was more adequate in trials with statistically
      significant results for efficacy, private funding, primary harms outcome, and
      anti-infective, antineoplasmatic, or immunosuppressive agents. CONCLUSION: The
      use of the Extension of the CONSORT statement may be associated with improving
      the quality of safety reporting in RCTs, but there are still deficiencies that
      need to be corrected to use quantitative objective evidence for harms in
      performing meta-analyses and making therapeutic decisions.

PMID- 21172602
TI  - Charlson and Rx-Risk comorbidity indices were predictive of mortality in the
      Australian health care setting.
AB  - OBJECTIVE: To compare the performance of Charlson index and Rx-Risk score using
      data from Australian Department of Veterans' Affairs. STUDY DESIGN AND SETTING: A
      study of older adults (N=94,714) who had both Charlson and Rx-Risk scores based
      on their hospital diagnoses and prescription medication dispensings during the
      baseline year (January 2005-December 2005). Predictive ability of 1-year and 3
      year mortality was compared by Akaike information criterion model fit statistic
      and c statistic in logistic regression models. We also compared the scores for
      identifying specific medical conditions. RESULTS: Both indices were significant
      predictors of all-cause mortality (P<0.0001). Of the population identified with a
      condition from either score, Rx-Risk score identified more than 95% of patients
      with gastric, respiratory, or cardiovascular condition, compared with Charlson
      index only identifying 2%, 31%, and 14%, respectively. The indices were
      comparable regarding diabetes. The Charlson index identified 83% of patients with
      dementia and 67% of those with cancers, whereas Rx-Risk score identified 38% and
      43%, respectively. CONCLUSION: Both the Charlson and Rx-Risk scores predict
      mortality, but neither index identified all comorbidities. Based on data
      availability, preferences, and research purposes, investigators can use either
      Charlson index or Rx-Risk score to adjust for comorbidity.

PMID- 21172603
TI  - Rate remapping: when the code goes beyond space.
AB  - Rate remapping is a conjunctive code that potentially enables hippocampal place
      cells to jointly represent spatial and nonspatial information. In this issue of
      Neuron, Renno-Costa et al. introduce a theoretical model wherein the convergence
      of the medial and lateral entorhinal excitatory inputs, combined with local
      inhibition, explains hippocampal rate remapping.

PMID- 21172604
TI  - In a pickle: is cornichon just relish or part of the main dish?
AB  - The recent discovery that vertebrate homologs of Drosophila cornichon associate
      with AMPA receptors led to the unexpected notion that cornichons play a role in
      synaptic transmission. In this issue of Neuron, Kato et al. find that cornichons
      modulate the gating of TARP-associated AMPA receptors by preventing their
      resensitization to glutamate.

PMID- 21172605
TI  - Multiple functions of the vesicular proton pump in nerve terminals.
AB  - Synaptic vesicles are acidified by a proton pump (vATPase), which allows
      vesicular uptake of neurotransmitters. After vesicle exocytosis, continued
      operation of the vATPase would seem to serve no useful function. In this issue of
      Neuron, however, Zhang and colleagues show that continued pumping alkalinizes the
      cytoplasm, accelerating endocytosis.

PMID- 21172607
TI  - An embedded subnetwork of highly active neurons in the neocortex.
AB  - VIDEO ABSTRACT: Unbiased methods to assess the firing activity of individual
      neurons in the neocortex have revealed that a large proportion of cells fire at
      extremely low rates (<0.1 Hz), both in their spontaneous and evoked activity.
      Thus, firing in neocortical networks appears to be dominated by a small
      population of highly active neurons. Here, we use a fosGFP transgenic mouse to
      examine the properties of cells with a recent history of elevated activity.
      FosGFP-expressing layer 2/3 pyramidal cells fired at higher rates compared to
      fosGFP(-) neurons, both in vivo and in vitro. Elevated activity could be
      attributed to increased excitatory and decreased inhibitory drive to fosGFP(+)
      neurons. Paired-cell recordings indicated that fosGFP(+) neurons had a greater
      likelihood of being connected to each other. These findings indicate that highly
      active, interconnected neuronal ensembles are present in the neocortex and
      suggest these cells may play a role in the encoding of sensory information.

PMID- 21172608
TI  - The mechanism of rate remapping in the dentate gyrus.
AB  - Rate remapping is a recently revealed neural code in which sensory information
      modulates the firing rate of hippocampal place cells. The mechanism underlying
      rate remapping is unknown. Its characteristic modulation, however, must arise
      from the interaction of the two major inputs to the hippocampus, the medial
      entorhinal cortex (MEC), in which grid cells represent the spatial position of
      the rat, and the lateral entorhinal cortex (LEC), in which cells represent the
      sensory properties of the environment. We have used computational methods to
      elucidate the mechanism by which this interaction produces rate remapping. We
      show that the convergence of LEC and MEC inputs, in conjunction with a
      competitive network process mediated by feedback inhibition, can account
      quantitatively for this phenomenon. The same principle accounts for why different
      place fields of the same cell vary independently as sensory information is
      altered. Our results show that rate remapping can be explained in terms of known
      mechanisms.

PMID- 21172609
TI  - Analysis of excitatory microcircuitry in the medial entorhinal cortex reveals
      cell-type-specific differences.
AB  - Medial entorhinal cortex (MEC) plays an important role in physiological processes
      underlying navigation, learning, and memory. Excitatory cells in the different
      MEC layers project in a region-specific manner to the hippocampus. However, the
      intrinsic microcircuitry of the main excitatory cells in the superficial MEC
      layers is largely unknown. Using scanning photostimulation, we investigated the
      functional microcircuitry of two such cell types, stellate and pyramidal cells.
      We found cell-type-specific intralaminar and ascending interlaminar feedback
      inputs. The ascending interlaminar inputs display distinct organizational
      principles depending on the cell-type and its position within the superficial
      lamina: the spatial spread of inputs for stellate cells is narrower than for
      pyramidal cells, while inputs to pyramidal cells in layer 3, but not in layer 2,
      exhibit an asymmetric offset to the medial side of the cell's main axis.
      Differential laminar sources of excitatory inputs might contribute to the
      functional diversity of stellate and pyramidal cells.

PMID- 21172606
TI  - Sleep state switching.
AB  - We take for granted the ability to fall asleep or to snap out of sleep into
      wakefulness, but these changes in behavioral state require specific switching
      mechanisms in the brain that allow well-defined state transitions. In this
      review, we examine the basic circuitry underlying the regulation of sleep and
      wakefulness and discuss a theoretical framework wherein the interactions between
      reciprocal neuronal circuits enable relatively rapid and complete state
      transitions. We also review how homeostatic, circadian, and allostatic drives
      help regulate sleep state switching and discuss how breakdown of the switching
      mechanism may contribute to sleep disorders such as narcolepsy.

PMID- 21172610
TI  - Tau mislocalization to dendritic spines mediates synaptic dysfunction
      independently of neurodegeneration.
AB  - The microtubule-associated protein tau accumulates in Alzheimer's and other fatal
      dementias, which manifest when forebrain neurons die. Recent advances in
      understanding these disorders indicate that brain dysfunction precedes
      neurodegeneration, but the role of tau is unclear. Here, we show that early tau
      related deficits develop not from the loss of synapses or neurons, but rather as
      a result of synaptic abnormalities caused by the accumulation of
      hyperphosphorylated tau within intact dendritic spines, where it disrupts
      synaptic function by impairing glutamate receptor trafficking or synaptic
      anchoring. Mutagenesis of 14 disease-associated serine and threonine amino acid
      residues to create pseudohyperphosphorylated tau caused tau mislocalization while
      creation of phosphorylation-deficient tau blocked the mistargeting of tau to
      dendritic spines. Thus, tau phosphorylation plays a critical role in mediating
      tau mislocalization and subsequent synaptic impairment. These data establish that
      the locus of early synaptic malfunction caused by tau resides in dendritic
      spines.

PMID- 21172611
TI  - Hippocampal AMPA receptor gating controlled by both TARP and cornichon proteins.
AB  - Transmembrane AMPA receptor regulatory proteins (TARPs) and cornichon proteins
      (CNIH-2/3) independently modulate AMPA receptor trafficking and gating. However,
      the potential for interactions of these subunits within an AMPA receptor complex
      is unknown. Here, we find that TARPs gamma-4, gamma-7, and gamma-8, but not gamma
      2, gamma-3, or gamma-5, cause AMPA receptors to "resensitize" upon continued
      glutamate application. With gamma-8, resensitization occurs with all GluA subunit
      combinations; however, gamma-8-containing hippocampal neurons do not display
      resensitization. In recombinant systems, CNIH-2 abrogates gamma-8-mediated
      resensitization and modifies AMPA receptor pharmacology and gating to match that
      of hippocampal neurons. In hippocampus, gamma-8 and CNIH-2 associate in
      postsynaptic densities and CNIH-2 protein levels are markedly diminished in gamma
      8 knockout mice. Manipulating neuronal CNIH-2 levels modulates the
      electrophysiological properties of extrasynaptic and synaptic gamma-8-containing
      AMPA receptors. Thus, gamma-8 and CNIH-2 functionally interact with common
      hippocampal AMPA receptor complexes to modulate synergistically kinetics and
      pharmacology.

PMID- 21172612
TI  - Vesicular ATPase inserted into the plasma membrane of motor terminals by
      exocytosis alkalinizes cytosolic pH and facilitates endocytosis.
AB  - Key components of vesicular neurotransmitter release, such as Ca(2+) influx and
      membrane recycling, are affected by cytosolic pH. We measured the pH-sensitive
      fluorescence of Yellow Fluorescent Protein transgenically expressed in mouse
      motor nerve terminals, and report that Ca(2+) influx elicited by action potential
      trains (12.5-100 Hz) evokes a biphasic pH change: a brief acidification (~ 13 nM
      average peak increase in [H(+)]), followed by a prolonged alkalinization (~ 30 nM
      peak decrease in [H(+)]) that outlasts the stimulation train. The alkalinization
      is selectively eliminated by blocking vesicular exocytosis with botulinum
      neurotoxins, and is prolonged by the endocytosis-inhibitor dynasore. Blocking
      H(+) pumping by vesicular H(+)-ATPase (with folimycin or bafilomycin) suppresses
      stimulation-induced alkalinization and reduces endocytotic uptake of FM1-43.
      These results suggest that H(+)-ATPase, known to transfer cytosolic H(+) into
      prefused vesicles, continues to extrude cytosolic H(+) after being exocytotically
      incorporated into the plasma membrane. The resulting cytosolic alkalinization may
      facilitate vesicular endocytosis.

PMID- 21172613
TI  - Presynaptic NMDARs in the hippocampus facilitate transmitter release at theta
      frequency.
AB  - A rise in [Ca(2+)](i) provides the trigger for neurotransmitter release at
      neuronal boutons. We have used confocal microscopy and Ca(2+) sensitive dyes to
      directly measure the action potential-evoked [Ca(2+)](i) in the boutons of
      Schaffer collaterals. This reveals that the trial-by-trial amplitude of the
      evoked Ca(2+) transient is bimodally distributed. We demonstrate that "large"
      Ca(2+) transients occur when presynaptic NMDA receptors are activated following
      transmitter release. Presynaptic NMDA receptor activation proves critical in
      producing facilitation of transmission at theta frequencies. Because large Ca(2+)
      transients "report" transmitter release, their frequency on a trial-by-trial
      basis can be used to estimate the probability of release, p(r). We use this novel
      estimator to show that p(r) increases following the induction of long-term
      potentiation.

PMID- 21172614
TI  - Homeostatic scaling requires group I mGluR activation mediated by Homer1a.
AB  - Homeostatic scaling is a non-Hebbian form of neural plasticity that maintains
      neuronal excitability and informational content of synaptic arrays in the face of
      changes of network activity. Here, we demonstrate that homeostatic scaling is
      dependent on group I metabotropic glutamate receptor activation that is mediated
      by the immediate early gene Homer1a. Homer1a is transiently upregulated during
      increases in network activity and evokes agonist-independent signaling of group I
      mGluRs that scales down the expression of synaptic AMPA receptors. Homer1a
      effects are dynamic and play a role in the induction of scaling. Similar to mGluR
      LTD, Homer1a-dependent scaling involves a reduction of tyrosine phosphorylation
      of GluA2 (GluR2), but is distinct in that it exploits a unique signaling property
      of group I mGluR to confer cell-wide, agonist-independent activation of the
      receptor. These studies reveal an elegant interplay of mechanisms that underlie
      Hebbian and non-Hebbian plasticity.

PMID- 21172615
TI  - Local presynaptic activity gates homeostatic changes in presynaptic function
      driven by dendritic BDNF synthesis.
AB  - Homeostatic synaptic plasticity is important for maintaining stability of
      neuronal function, but heterogeneous expression mechanisms suggest that distinct
      facets of neuronal activity may shape the manner in which compensatory synaptic
      changes are implemented. Here, we demonstrate that local presynaptic activity
      gates a retrograde form of homeostatic plasticity induced by blockade of AMPA
      receptors (AMPARs) in cultured hippocampal neurons. We show that AMPAR blockade
      produces rapid (<3 hr) protein synthesis-dependent increases in both presynaptic
      and postsynaptic function and that the induction of presynaptic, but not
      postsynaptic, changes requires coincident local activity in presynaptic
      terminals. This "state-dependent" modulation of presynaptic function requires
      postsynaptic release of brain-derived neurotrophic factor (BDNF) as a retrograde
      messenger, which is locally synthesized in dendrites in response to AMPAR
      blockade. Taken together, our results reveal a local crosstalk between active
      presynaptic terminals and postsynaptic signaling that dictates the manner by
      which homeostatic plasticity is implemented at synapses.

PMID- 21172616
TI  - Role of ACh-GABA cotransmission in detecting image motion and motion direction.
AB  - Starburst amacrine cells (SACs) process complex visual signals in the retina
      using both acetylcholine (ACh) and gamma-aminobutyric acid (GABA), but the
      synaptic organization and function of ACh-GABA corelease remain unclear. Here, we
      show that SACs make cholinergic synapses onto On-Off direction-selective ganglion
      cells (DSGCs) from all directions but make GABAergic synapses onto DSGCs only
      from the null direction. ACh and GABA were released differentially in a Ca(2+)
      level-specific manner, suggesting the two transmitters were released from
      different vesicle populations. Despite the symmetric cholinergic connection, the
      light-evoked cholinergic input to a DSGC, detected at both light onset and
      offset, was motion- and direction-sensitive. This input was facilitated by two
      spot apparent motion in the preferred direction but supressed in the null
      direction, presumably by a GABAergic mechanism. The results revealed a high level
      of synaptic intricacy in the starburst circuit and suggested differential, yet
      synergistic, roles of ACh-GABA cotransmission in motion sensitivity and direction
      selectivity.

PMID- 21172617
TI  - Functional organization of a neural network for aversive olfactory learning in
      Caenorhabditis elegans.
AB  - Many animals use their olfactory systems to learn to avoid dangers, but how
      neural circuits encode naive and learned olfactory preferences, and switch
      between those preferences, is poorly understood. Here, we map an olfactory
      network, from sensory input to motor output, which regulates the learned
      olfactory aversion of Caenorhabditis elegans for the smell of pathogenic
      bacteria. Naive animals prefer smells of pathogens but animals trained with
      pathogens lose this attraction. We find that two different neural circuits
      subserve these preferences, with one required for the naive preference and the
      other specifically for the learned preference. Calcium imaging and behavioral
      analysis reveal that the naive preference reflects the direct transduction of the
      activity of olfactory sensory neurons into motor response, whereas the learned
      preference involves modulations to signal transduction to downstream neurons to
      alter motor response. Thus, two different neural circuits regulate a behavioral
      switch between naive and learned olfactory preferences.

PMID- 21172619
TI  - Current biology at 20.

PMID- 21172618
TI  - Membrane potential synchrony in primary visual cortex during sensory stimulation.
AB  - When the primary visual cortex (V1) is activated by sensory stimulation, what is
      the temporal correlation between the synaptic inputs to nearby neurons? This
      question underlies the origin of correlated activity, the mechanism of how
      visually evoked activity emerges and propagates in cortical circuits, and the
      relationship between spontaneous and evoked activity. Here, we have recorded
      membrane potential from pairs of V1 neurons in anesthetized cats and found that
      visual stimulation suppressed low-frequency membrane potential synchrony (0-10
      Hz), and often increased synchrony at high frequencies (20-80 Hz). The increase
      in high-frequency synchrony occurred for neurons with similar orientation
      preferences and for neurons with different orientation preferences and occurred
      for a wide range of stimulus orientations. Thus, while only a subset of neurons
      spike in response to visual stimulation, a far larger proportion of the circuit
      is correlated with spiking activity through subthreshold, high-frequency
      synchronous activity that crosses functional domains.

PMID- 21172620
TI  - Bats.

PMID- 21172621
TI  - Adhesion signalling complexes.
AB  - Intercellular communication in metazoa not only requires autocrine, paracrine and
      exocrine signalling systems, but it also relies on the structural and positional
      information encoded in extracellular matrices (ECMs). Most cells in tissues are
      structurally and functionally integrated with their surrounding ECM in a highly
      organised manner involving thousands of dynamic connections. On the intracellular
      face of these linkages, adhesion receptors - principally integrins and syndecans 
      link the cytoskeleton to the plasma membrane and compartmentalise cytoplasmic
      signalling events, whereas at the extracellular face the same receptors direct
      and organise the deposition of the ECM itself. Adhesion receptors transduce
      mechanical force bidirectionally across the plasma membrane by tethering variably
      deformable ECMs to the contractile cytoskeleton (Figure 1), and they translate
      the topography and composition of the ECM into chemical signals that determine
      behaviour. The membrane-proximal functions of adhesion receptors in turn trigger
      distal processes within cells, such as alterations in the direction of cell
      movement and the regulation of gene transcription, and long-range effects outside
      cells, such as the construction of ECM networks and consequent shaping of higher
      order tissue structure. Given the diverse and fundamental roles attributed to
      adhesion, it is understandable that adhesion receptor engagement has been
      reported to alter the flux through virtually all major signalling pathways.

PMID- 21172622
TI  - Sex differences in chimpanzees' use of sticks as play objects resemble those of
      children.

PMID- 21172623
TI  - Centrosome biogenesis: centrosomin sizes things up!
AB  - Centrosomes are composed of a centriole pair surrounded by a proteinaceous matrix
      of pericentriolar material that contains protein complexes required for
      microtubule nucleation and anchoring. Recent work reveals an intriguing link
      between centrioles and pericentriolar material that is involved in modulating
      centrosome size.

PMID- 21172624
TI  - Social cognition: feeling voices to recognize emotions.
AB  - Our understanding of how we simulate other people's actions and feelings to
      recognize their emotional states is extended by a new study which finds that
      premotor and somatosensory cortices are required to process the emotional meaning
      of sounds.

PMID- 21172625
TI  - Speciation genetics: search for the missing snowball.
AB  - Theory predicts that, as species diverge from one another, the number of genetic
      incompatibilities causing sterility or inviability in interspecies hybrids grows
      faster than linearly, or snowballs. Two new genetic analyses now provide the
      first empirical support for this snowball effect.

PMID- 21172626
TI  - Primatology: monkey bromance.
AB  - Male macaques form strong social bonds that enhance competitive ability and
      mating success, belying theoretical predictions that mate competition should
      prevent males from cooperating with one another.

PMID- 21172627
TI  - Aging: miRacles of longevity?
AB  - The inventory of processes that miRNAs regulate has continued to expand since
      their relatively recent discovery. A new study reveals not only that the
      expression of miRNAs changes with age, but also that these miRNAs can act in both
      pro- and anti-longevity regulatory pathways.

PMID- 21172628
TI  - Eukaryotic evolution: the importance of being archaebacterial.
AB  - Approximately half of all eukaryotic genes show signs of prokaryotic origin.
      Genes derived from eubacteria are more abundant than those from archaebacteria,
      but the latter are functionally more important. This supports archaebacteria as
      founding ancestors of the eukaryotic nucleus.

PMID- 21172629
TI  - Sex allocation: size matters for red spider mites.
AB  - Many animals can adjust the sex ratio of their offspring according to their
      parental ability to invest. In spider mites, larger eggs are likely to be
      fertilized and produce diploid females, whereas smaller eggs produce haploid
      males.

PMID- 21172630
TI  - Fruit development: new directions for an old pathway.
AB  - A recent study investigating the molecular mechanisms of seed pod shattering has
      shown that the basic helix-loop-helix (bHLH) proteins INDEHISCENT and ALCATRAZ
      appear to regulate fruit patterning through gibberellic acid (GA)-DELLA
      signalling, revealing a central role for bHLH family members in GA response
      specificity.

PMID- 21172631
TI  - Kinetochores: NDC80 toes the line.
AB  - Kinetochore-associated NDC80 complexes serve as the primary binding site for the
      plus-ends of spindle microtubules in mitosis. A recent study proposes a novel
      mechanism for regulating kinetochore-microtubule binding involving NDC80 complex
      oligomerization, which could be mediated by Aurora B kinase.

PMID- 21172632
TI  - Ambient thermometers in plants: from physiological outputs towards mechanisms of
      thermal sensing.
AB  - Plants respond to ambient temperature changes over a series of timescales.
      Genetic and physiological studies over the last decades have revealed myriad
      thermally sensitive pathways in plants. A recent study provides a genetic and
      biochemical mechanistic description of how thermal changes can be transduced to
      influence gene expression. What remains to be revealed in this, and other
      thermally controlled responses, is a description of the primary temperature
      sensing event. Cooling and warming alter membrane fluidity and elicit
      intracellular free-calcium elevations, a process that has been considered the
      primary event controlling plant responses to temperature. Such direct thermal
      sensors appear to process temperature information. Future efforts will be
      required to identify the effector proteins linking perception to response. This
      review considers the evidence for plant thermometers to date, provides a
      description of several notable physiological and developmental processes under
      ambient temperature control, and outlines major questions that remain to be
      addressed in the understanding of thermometers in plants.

PMID- 21172633
TI  - The state of research in the realm of foot and ankle surgery.

PMID- 21172638
TI  - Total ankle replacement in the varus ankle.
AB  - Treatment of ankle varus with total ankle replacement (TAR) lacks consensus
      regarding the limits of deformity that can be managed successfully without
      recurrence. With newer anatomic prosthetic designs and a comprehensive surgical
      approach, treatment of frontal plane deformities with implant arthroplasty has
      gained acceptance. The purpose of this retrospective study was to determine the
      outcome and compare correction of large frontal plane varus deformities with TAR
      using 2 different replacement systems. Also, a stepwise surgical approach for
      consistent correction was determined. TAR was performed on 26 patients with varus
      ankle deformity and a mean age of 63.85 +/- 9.33 (range 48-86) years. Duration of
      follow-up was 16.69 +/- 7.26 (range 7-37) months. The difference between the
      immediate postoperative frontal plane radiographic alignments was compared with
      the preoperative deformity, and reevaluated after at least 1 year of weight
      bearing function. The preoperative mortise view varus deformity was 16.8 degrees 
      +/- 6.79 degrees  (range 6 degrees -28 degrees ), whereas at final follow-up the
      degree of varus was 0 degrees  +/- 2.64 degrees  (P < .0001) on the
      anteroposterior view and 0.5 degrees  +/- 2.7 degrees  (P < .0001) on the mortise
      view. All but one patient was corrected to within 4 degrees  of frontal plane
      neutral. Overall, correction was maintained throughout the study period. In
      conclusion, surgical treatment of the varus ankle arthrosis with TAR can be
      successful.

PMID- 21172639
TI  - Arthrodesis with internal fixation of the infected ankle.
AB  - Arthrodesis may be necessary to avoid amputation when treating an infected
      tibiotalar joint. In such cases, external or hybrid fixation is usually used. In
      this retrospective study, we report our experience in treating tibiotalar joint
      infection by arthrodesis with internal fixation. From March 1992 to October 2005
      (13 years, 7 months), 20 patients underwent septic ankle arthrodesis with
      internal fixation. The mean duration of infection before fusion was 2.5 +/- 6.7
      years. Arthrodesis was performed with the Meary technique in 9 (45%) cases and
      with the Crawford-Adams technique in 11 (55%) cases. Internal fixation consisted
      of screw fixation, staple fixation, or a combination of both. The mean duration
      of antibiotic treatment was 97.5 +/- 37.5 days, and the mean follow-up was 64 +/-
      36 months, with no patient lost to follow-up. Patients were considered cured if
      no clinical, biological, or radiologic signs of infection were present at a
      minimum of 2 years follow-up. The incidence of cure was 85.0% (91.0% with
      Crawford-Adams and 77.8% with Meary techniques). Radiographic fusion was
      identified in 89.5% of the cases (91.0% with Crawford-Adams and 87.5% with Meary
      techniques) at a mean of 4.8 +/- 2.4 (range 3 to 11) months postoperative.
      Tibiotalar arthrodesis in the presence of sepsis can be performed with internal
      osteosynthesis only under certain conditions. In our experience, this treatment
      produced satisfactory fusion in 89.5% of patients and eradicated infection in
      85.0% of cases.

PMID- 21172640
TI  - Variability of insertion of the Achilles tendon on the calcaneus: an MRI study of
      younger subjects.
AB  - The insertional location of the Achilles tendon traditionally has been thought to
      be on the superior aspect of the calcaneus. This is based on descriptions and
      illustrations in anatomical textbooks. Our study is a digital magnetic resonance
      imaging (MRI) examination of the insertional location of the Achilles tendon in
      69 subjects, 12 to 40 years of age. A midsagittal slice of the ankle was used to
      identify the most distal insertional location of the Achilles tendon on the
      posterior aspect of the calcaneus. The superior and inferior margins of the
      posterior aspect of the calcaneus were measured and the Achilles tendon insertion
      was calculated as a percentage of the total length of the posterior aspect of the
      calcaneus. Our results revealed that there is a statistically significant
      difference in the insertional location as related to age. Additionally, there is
      a statistically significant proximal migration (0.63%) of the insertional
      location with each advancing year. Based on our results, it appears that there is
      an inaccurate depiction in the anatomical literature, which may necessitate a
      change in the approach to pathologic conditions associated with the Achilles
      tendon.

PMID- 21172641
TI  - Inverted Z-scarf osteotomy for hallux valgus deformity correction: intermediate
      term results in 55 patients.
AB  - The Z-scarf osteotomy is used for hallux valgus deformity correction by foot and
      ankle surgeons worldwide. Inverting the Z-scarf osteotomy configuration
      strengthens the construct in both sawbone and cadaver models, but clinical
      results of this configuration have not been reported in the literature. This
      retrospective study evaluates the subjective and intermediate-term postoperative
      radiographic results of 73 inverted Z-scarf osteotomy procedures for hallux
      valgus correction in 55 patients from January 1994 to December 2003. The modified
      University of Maryland 100-Point Painful Foot Center Scoring System demonstrated
      52 patients (95%) with good to excellent results at a mean follow-up of 5 years
      (range 2-11 years). Radiograph measurements revealed the following: first-second
      intermetatarsal angle mean, 6.1 degrees  (range 2-14 degrees ), average reduction
      4.6 degrees ; hallux abductus angle mean, 11.0 degrees  (range -8-30 degrees ),
      average reduction 10.1 degrees ; tibial sesamoid position mean, 2.3; first
      metatarsal protrusion distance mean, -2.1 mm. Two patients (2 of 73 feet)
      developed major complications: one progressed to clinically acceptable hallux
      varus; another sustained compromise of one fixation screw with minor displacement
      at the distal osteotomy that healed in satisfactory position after non-weight
      bearing immobilization. There were no cases of osteonecrosis, delayed union, or
      nonunion. The inverted Z-scarf osteotomy, with advantages in both mechanical
      strength and technique of execution over the traditional configuration,
      demonstrates high patient satisfaction, restoration of normal radiographic
      parameters, and a low complication rate in this study.

PMID- 21172642
TI  - Evidence-based treatment of maisonneuve fractures.
AB  - The objective of the current study was to review the published clinical evidence
      available for the treatment of Maisonneuve fractures. Medline via PubMed,
      Orthopaedic Trauma Association (OTA) annual meetings' abstracts archives Web
      site, Embase, the Cochrane Database of Systematic Reviews, and the Cochrane
      Clinical Trial register were searched for the period extending from January 1970
      to May 2009 in order to identify studies relating to the treatment of Maisonneuve
      ankle fractures. Six level 4 (case series, N >= 5) studies, describing a total of
      83 patients with a Maisonneuve fracture, were included in the review. Although
      the authors did not compare the different treatment strategies described in the
      reports, the overall outcomes were generally good, and included 74 (89%) patients
      in which the outcome was considered good or excellent, and 9 (11%) patients in
      which the outcome was considered fair or poor. Based on this review, some grade B
      and C recommendations for the treatment of Maisonneuve fractures were formulated,
      including: 1) the medial malleolus should be fixated, 2) the torn deltoid
      ligament need not be directly repaired, 3) syndesmotic instability can be treated
      with one or two 3- or 4-cortical screws and these can be placed percutaneously,
      and 4) the proximal fibular fracture does not require direct internal fixation.
      Recommendations for future research were also formulated and described in this
      report.

PMID- 21172643
TI  - Payments for surgical services and the medical inflation rate.

PMID- 21172644
TI  - Pigmented villonodular synovitis of the ankle-radiation therapy as a primary
      treatment to reduce recurrence: a case report with 8-year follow-up.
AB  - Pigmented villonodular synovitis (PVNS) is a rare, benign, idiopathic
      proliferative disorder of the synovium that results in villous and or nodular
      formations that have been reported to manifest within joints, tendon sheaths, and
      bursae. The overall incidence includes 2% to 10% that occur within the foot and
      ankle joints. PVNS has a high rate of recurrence and up to a 45% recurrence rate
      has been reported despite surgical intervention. Although traditional treatment
      for PVNS includes synovectomy with arthroplasty of the affected joint, radiation
      therapy is now suggested as an adjunctive therapy that is believed to reduce
      recurrence of the disease. We present a case of PVNS where the patient was
      treated in 2 stages: surgical resection of the tumor with arthroplasty of the
      ankle joint followed by radiation therapy. A retrospective review of the chart,
      radiographs, and MRIs was conducted for a 36-year-old, African American female
      who had been treated and followed for 8 years. Pathologic examination of the
      tumor confirmed the diagnosis of PVNS. No evidence of recurrent PVNS was
      identified in the long-term postoperative MRI examination. The fact that
      ancillary imaging examinations failed to reveal evidence of recurrence and that
      the patient expresses a very high patient satisfaction supports the potential
      benefit of adjunctive radiation therapy for this condition.

PMID- 21172645
TI  - Synovial sarcoma arising in the foot: case report.
AB  - Synovial sarcomas occur primarily in the soft tissue structures adjacent to the
      joints and tendons of the extremities. A diagnostic dilemma exists when the
      clinical presentation is similar to that of an infection or soft tissue trauma.
      We report a case of soft tissue sarcoma of the foot in a previously healthy 19
      year-old male who presented after hitting his right foot against a refrigerator.
      Initial radiographs were negative; however, 6 weeks later plain radiographs
      revealed destruction of the metatarsals. Histologic analysis on a specimen
      obtained via fine-needle aspiration confirmed the diagnosis of primary synovial
      sarcoma. Further workup revealed metastases to the lungs. An amputation at
      Chopart's joint was performed. Primary synovial sarcoma in the foot can mimic
      infection or edema from a traumatic event. Clinicians should always be suspicious
      of soft tissue masses and keep neoplastic processes in the list of differentials.

PMID- 21172646
TI  - A report of a rare phalangeal periosteal chondroma of the foot.
AB  - Periosteal chondroma is a benign, slow-growing cartilaginous tumor that typically
      occurs at the metaphysis of long tubular bones beneath the periosteal membrane. A
      case is presented of a 42-year-old male who developed a firm, tender, uneven mass
      encircling the lateral, dorsal, and medial aspects of the right second proximal
      phalanx following a traumatic event. The mass was excised en toto and
      histopathologic findings are presented.

PMID- 21172648
TI  - UNCovering the molecular machinery of dependence receptor signaling.
AB  - Dependence receptors send opposite signals in the presence or absence of ligand,
      but the underlying mechanisms have been elusive. In this issue of Molecular Cell,
      Guenebeaud et al. (2010) elucidate the molecular signaling machinery of the
      dependence receptor UNC5B.

PMID- 21172649
TI  - Targeted ubiquitylation: the prey becomes predator.
AB  - Being targeted for polyubiquitylation often means the end of life for the
      substrate protein. In this issue of Molecular Cell, Ouni et al. (2010)
      demonstrate that the yeast transcription factor Met4, a target of the SCF(Met30)
      E3 ligase for nonproteolytic polyubiquitylation, can also function to target its
      cofactors for proteolytic ubiquitylation by the same E3 ligase.

PMID- 21172650
TI  - The three Rs of transcription: recruit, retain, and recycle.
AB  - The dynamic protein interactions required for transcription are functionally
      important yet poorly understood; in this issue of Molecular Cell, Zobeck et al.
      (2010) resolve the sequential recruitment and selective recycling of
      transcription factors at an actively transcribing locus in Drosophila.

PMID- 21172651
TI  - Seeking resolution: budding yeast enzymes finally make the cut.
AB  - Genetic studies reported in Molecular Cell (Ho et al., 2010) identify Mus81-Mms4
      and Yen1 as the structure-specific endonucleases that cleave most Holliday
      junctions. A failure in this key step has profound effects on mitotic genome
      stability.

PMID- 21172652
TI  - DNA replication: making two forks from one prereplication complex.
AB  - The copying of chromosomal DNA initiates from a single nucleoprotein assembly
      called the prereplication complex. New findings in a recent issue of Molecular
      Cell (Yardimci et al., 2010) reveal that this complex dissolves into two
      independent replisomes that move away from each other as DNA synthesis ensues.

PMID- 21172653
TI  - The dependence receptor UNC5H2/B triggers apoptosis via PP2A-mediated
      dephosphorylation of DAP kinase.
AB  - The UNC5H dependence receptors promote apoptosis in the absence of their ligand,
      netrin-1, and this is important for neuronal and vascular development and for
      limitation of cancer progression. UNC5H2 (also called UNC5B) triggers cell death
      through the activation of the serine-threonine protein kinase DAPk. While
      performing a siRNA screen to identify genes implicated in UNC5H-induced
      apoptosis, we identified the structural subunit PR65beta of the holoenzyme
      protein phosphatase 2A (PP2A). We show that UNC5H2/B recruits a protein complex
      that includes PR65beta and DAPk and retains PP2A activity. PP2A activity is
      required for UNC5H2/B-induced apoptosis, since it activates DAPk by triggering
      its dephosphorylation. Moreover, netrin-1 binding to UNC5H2/B prevents this
      effect through interaction of the PP2A inhibitor CIP2A to UNC5H2/B. Thus we show
      here that, in the absence of netrin-1, recruitment of PP2A to UNC5H2/B allows the
      activation of DAPk via a PP2A-mediated dephosphorylation and that this mechanism
      is involved in angiogenesis regulation.

PMID- 21172654
TI  - Identification of the Rac-GEF P-Rex1 as an essential mediator of ErbB signaling
      in breast cancer.
AB  - While the small GTPase Rac1 and its effectors are well-established mediators of
      mitogenic and motile signaling by tyrosine kinase receptors and have been
      implicated in breast tumorigenesis, little is known regarding the exchange
      factors (Rac-GEFs) that mediate ErbB receptor responses. Here, we identify the
      PIP(3)-Gbetagamma-dependent Rac-GEF P-Rex1 as an essential mediator of Rac1
      activation, motility, cell growth, and tumorigenesis driven by ErbB receptors in
      breast cancer cells. Notably, activation of P-Rex1 in breast cancer cells
      requires the convergence of inputs from ErbB receptors and a Gbetagamma- and
      PI3Kgamma-dependent pathway. Moreover, we identified the GPCR CXCR4 as a crucial
      mediator of P-Rex1/Rac1 activation in response to ErbB ligands. P-Rex1 is highly
      overexpressed in human breast cancers and their derived cell lines, particularly
      those with high ErbB2 and ER expression. In addition to the prognostic and
      therapeutic implications, our findings reveal an ErbB effector pathway that is
      crucial for breast cancer progression.

PMID- 21172655
TI  - Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates
      MnSOD activity in response to stress.
AB  - Genetic deletion of the mitochondrial deacetylase sirtuin-3 (Sirt3) results in
      increased mitochondrial superoxide, a tumor-permissive environment, and mammary
      tumor development. MnSOD contains a nutrient- and ionizing radiation (IR)
      dependent reversible acetyl-lysine that is hyperacetylated in Sirt3-/- livers at
      3 months of age. Livers of Sirt3-/- mice exhibit decreased MnSOD activity, but
      not immunoreactive protein, relative to wild-type livers. Reintroduction of wild
      type but not deacetylation null Sirt3 into Sirt3-/- MEFs deacetylated lysine and
      restored MnSOD activity. Site-directed mutagenesis of MnSOD lysine 122 to an
      arginine, mimicking deacetylation (lenti-MnSOD(K122-R)), increased MnSOD activity
      when expressed in MnSOD-/- MEFs, suggesting acetylation directly regulates
      function. Furthermore, infection of Sirt3-/- MEFs with lenti-MnSOD(K122-R)
      inhibited in vitro immortalization by an oncogene (Ras), inhibited IR-induced
      genomic instability, and decreased mitochondrial superoxide. Finally, IR was
      unable to induce MnSOD deacetylation or activity in Sirt3-/- livers, and these
      irradiated livers displayed significant IR-induced cell damage and
      microvacuolization in their hepatocytes.

PMID- 21172656
TI  - Structural basis for oligosaccharide recognition of misfolded glycoproteins by OS
      9 in ER-associated degradation.
AB  - Misfolded glycoproteins are translocated from endoplasmic reticulum (ER) into the
      cytosol for proteasome-mediated degradation. A mannose-6-phosphate receptor
      homology (MRH) domain is commonly identified in a variety of proteins and, in the
      case of OS-9 and XTP3-B, is involved in glycoprotein ER-associated degradation
      (ERAD). Trimming of outermost alpha1,2-linked mannose on C-arm of high-mannose
      type glycan and binding of processed alpha1,6-linked mannosyl residues by the MRH
      domain are critical steps in guiding misfolded glycoproteins to enter ERAD. Here
      we report the crystal structure of a human OS-9 MRH domain (OS-9(MRH)) complexed
      with alpha3,alpha6-mannopentaose. The OS-9(MRH) has a flattened beta-barrel
      structure with a characteristic P-type lectin fold and possesses distinctive
      double tryptophan residues in the oligosaccharide-binding site. Our
      crystallographic result in conjunction with nuclear magnetic resonance (NMR)
      spectroscopic and biochemical results provides structural insights into the
      mechanism whereby OS-9 specifically recognizes Manalpha1,6Manalpha1,6Man residues
      on the processed C-arm through the continuous double tryptophan (WW) motif.

PMID- 21172657
TI  - Ubiquitylation of an ERAD substrate occurs on multiple types of amino acids.
AB  - Any protein synthesized in the secretory pathway has the potential to misfold and
      would need to be recognized and ubiquitylated for degradation. This is
      astounding, since only a few ERAD-specific E3 ligases have been identified. To
      begin to understand substrate recognition, we wished to map the ubiquitylation
      sites on the NS-1 nonsecreted immunoglobulin light chain, which is an ERAD
      substrate. Ubiquitin is usually attached to lysine residues and less frequently
      to the N terminus of proteins. In addition, several viral E3s have been
      identified that attach ubiquitin to cysteine or serine/threonine residues.
      Mutation of lysines, serines, and threonines in the NS-1 variable region was
      necessary to significantly reduce ubiquitylation and stabilize the protein. The
      Hrd1 E3 ligase was required to modify all three amino acids. Our studies argue
      that ubiquitylation of ER proteins relies on very different mechanisms of
      recognition and modification than those used to regulate biological processes.

PMID- 21172658
TI  - 3D cryo-EM structure of an active step I spliceosome and localization of its
      catalytic core.
AB  - The spliceosome excises introns from pre-mRNA in a two-step splicing reaction. So
      far, the three-dimensional (3D) structure of a spliceosome with preserved
      catalytic activity has remained elusive. Here, we determined the 3D structure of
      the human, catalytically active step I spliceosome (C complex) by cryo-electron
      microscopy (cryo-EM) in vitrified ice. Via immunolabeling we mapped the position
      of the 5' exon. The C complex contains an unusually salt-stable ribonucleoprotein
      (RNP) core that harbors its catalytic center. We determined the 3D structure of
      this RNP core and also that of a post-step II particle, the 35S U5 snRNP, which
      contains most of the C complex core proteins. As C complex domains could be
      recognized in these structures, their position in the C complex could be
      determined, thereby allowing the region harboring the spliceosome's catalytic
      core to be localized.

PMID- 21172659
TI  - Genome-wide identification of polycomb-associated RNAs by RIP-seq.
AB  - Polycomb proteins play essential roles in stem cell renewal and human disease.
      Recent studies of HOX genes and X inactivation have provided evidence for RNA
      cofactors in Polycomb repressive complex 2 (PRC2). Here we develop a RIP-seq
      method to capture the PRC2 transcriptome and identify a genome-wide pool of >9000
      PRC2-interacting RNAs in embryonic stem cells. The transcriptome includes
      antisense, intergenic, and promoter-associated transcripts, as well as many
      unannotated RNAs. A large number of transcripts occur within imprinted regions,
      oncogene and tumor suppressor loci, and stem cell-related bivalent domains. We
      provide evidence for direct RNA-protein interactions, most likely via the Ezh2
      subunit. We also identify Gtl2 RNA as a PRC2 cofactor that directs PRC2 to the
      reciprocally imprinted Dlk1 coding gene. Thus, Polycomb proteins interact with a
      genome-wide family of RNAs, some of which may be used as biomarkers and
      therapeutic targets for human disease.

PMID- 21172660
TI  - A transcriptional activator is part of an SCF ubiquitin ligase to control
      degradation of its cofactors.
AB  - Multisubunit protein complexes pose a challenge to the coordinated regulation of
      individual components. We show how the yeast transactivating factor Met4
      functions as a component of the SCF(Met30) ubiquitin ligase to synchronize its
      own activity with cofactor assembly. Cells maintain Met4 in a dormant state by a
      regulatory ubiquitin chain assembled by SCF(Met30). Nutritional and heavy-metal
      stress block Met4 ubiquitylation resulting in Met4 activation, which induces a
      stress-response program including cell-cycle arrest. Met4 relies on assembly with
      various cofactors for promoter binding. We report here that the stability of
      these DNA-binding cofactors is regulated by SCF(Met30). Remarkably, the
      transcriptional activator Met4 functions as a substrate-specificity factor in the
      context of SCF(Met30/Met4) to coordinate cofactor degradation with its own
      activity status. Our results establish an additional layer for substrate
      recruitment by SCF ubiquitin ligases and provide conceptual insight into
      coordinated regulation of protein complexes.

PMID- 21172661
TI  - Recruitment timing and dynamics of transcription factors at the Hsp70 loci in
      living cells.
AB  - Chromatin immunoprecipitation (ChIP) studies provide snapshots of factors on
      chromatin in cell populations. Here, we use live-cell imaging to examine at high
      temporal resolution the recruitment and dynamics of transcription factors to the
      inducible Hsp70 loci in individual Drosophila salivary gland nuclei. Recruitment
      of the master regulator, HSF, is first detected within 20 s of gene activation;
      the timing of its recruitment resolves from RNA polymerase II and P-TEFb, and
      these factors resolve from Spt6 and Topo I. Remarkably, the recruitment of each
      factor is highly synchronous between different cells. In addition, fluorescence
      recovery after photobleaching (FRAP) analyses show that the entry and exit of
      multiple factors are progressively constrained upon gene activation, suggesting
      the gradual formation of a transcription compartment. Furthermore, we demonstrate
      that poly(ADP-ribose) (PAR) polymerase activity is required to maintain the
      transcription compartment. We propose that PAR polymers locally retain factors in
      a transcription compartment.

PMID- 21172662
TI  - The ACF1 complex is required for DNA double-strand break repair in human cells.
AB  - DNA double-strand breaks (DSBs) are repaired via nonhomologous end-joining (NHEJ)
      or homologous recombination (HR), but cellular repair processes remain elusive.
      We show here that the ATP-dependent chromatin-remodeling factors, ACF1 and SNF2H,
      accumulate rapidly at DSBs and are required for DSB repair in human cells. If the
      expression of ACF1 or SNF2H is suppressed, cells become extremely sensitive to X
      rays and chemical treatments producing DSBs, and DSBs remain unrepaired. ACF1
      interacts directly with KU70 and is required for the accumulation of KU proteins
      at DSBs. The KU70/80 complex becomes physically more associated with the
      chromatin-remodeling factors of the CHRAC complex, which includes ACF1, SNF2H,
      CHRAC15, and CHRAC17, after treatments producing DSBs. Furthermore, the frequency
      of NHEJ as well as HR induced by DSBs in chromosomal DNA is significantly
      decreased in cells depleted of either of these factors. Thus, ACF1 and its
      complexes play important roles in DSBs repair.

PMID- 21172663
TI  - Mus81 and Yen1 promote reciprocal exchange during mitotic recombination to
      maintain genome integrity in budding yeast.
AB  - Holliday junction (HJ) resolution is required for segregation of chromosomes and
      for formation of crossovers during homologous recombination. The identity of the
      resolvase(s) that functions in vivo has yet to be established, although several
      proteins able to cut HJs in vitro have been identified as candidates in yeasts
      and mammals. Using an assay to detect unselected products of mitotic
      recombination, we found a significant decrease in crossovers in the Saccharomyces
      cerevisiae mus81Delta mutant. Yen1 serves a backup function responsible for
      resolving intermediates in mus81Delta mutants, or when conversion tracts are
      short. In the absence of both Mus81 and Yen1, intermediates are not channeled
      exclusively to noncrossover recombinants, but instead are processed by Pol32
      dependent break-induced replication (BIR). The channeling of recombination from
      reciprocal exchange to BIR results in greatly increased spontaneous loss of
      heterozygosity (LOH) and chromosome mis-segregation in the mus81Delta yen1Delta
      mutant, typical of the genomic instability found in tumor cells.

PMID- 21172667
TI  - Childhood tuberculosis - a new era.

PMID- 21172665
TI  - TDRD3 is an effector molecule for arginine-methylated histone marks.
AB  - Specific sites of histone tail methylation are associated with transcriptional
      activity at gene loci. These methyl marks are interpreted by effector molecules,
      which harbor protein domains that bind the methylated motifs and facilitate
      either active or inactive states of transcription. CARM1 and PRMT1 are
      transcriptional coactivators that deposit H3R17me2a and H4R3me2a marks,
      respectively. We used a protein domain microarray approach to identify the Tudor
      domain-containing protein TDRD3 as a "reader" of these marks. Importantly, TDRD3
      itself is a transcriptional coactivator. This coactivator activity requires an
      intact Tudor domain. TDRD3 is recruited to an estrogen-responsive element in a
      CARM1-dependent manner. Furthermore, ChIP-seq analysis of TDRD3 reveals that it
      is predominantly localized to transcriptional start sites. Thus, TDRD3 is an
      effector molecule that promotes transcription by binding methylarginine marks on
      histone tails.

PMID- 21172664
TI  - Temporally and biochemically distinct activities of Exo1 during meiosis: double
      strand break resection and resolution of double Holliday junctions.
AB  - The Rad2/XPG family nuclease, Exo1, functions in a variety of DNA repair
      pathways. During meiosis, Exo1 promotes crossover recombination and thereby
      facilitates chromosome segregation at the first division. Meiotic recombination
      is initiated by programmed DNA double-strand breaks (DSBs). Nucleolytic resection
      of DSBs generates long 3' single-strand tails that undergo strand exchange with a
      homologous chromosome to form joint molecule (JM) intermediates. We show that
      meiotic DSB resection is dramatically reduced in exo1Delta mutants and test the
      idea that Exo1-catalyzed resection promotes crossing over by facilitating
      formation of crossover-specific JMs called double Holliday junctions (dHJs).
      Contrary to this idea, dHJs form at wild-type levels in exo1Delta mutants,
      implying that Exo1 has a second function that promotes resolution of dHJs into
      crossovers. Surprisingly, the dHJ resolution function of Exo1 is independent of
      its nuclease activities but requires interaction with the putative endonuclease
      complex, Mlh1-Mlh3. Thus, the DSB resection and procrossover functions of Exo1
      during meiosis involve temporally and biochemically distinct activities.

PMID- 21172668
TI  - Immunology and pathogenesis of childhood TB.

PMID- 21172669
TI  - Immune-based diagnostics for TB in children: what is the evidence?
AB  - Childhood TB is difficult to diagnose, since disease tends to be paucibacillary
      and sputum specimens are not easy to obtain in children. Thus, blood-based immune
      assays are an attractive option. Systematic reviews of serological assays suggest
      that these tests produce highly inconsistent estimates of sensitivity and
      specificity, but much of the serology literature is based on adults. In children,
      there is insufficient evidence to recommend the use of serological tests for
      active TB diagnosis. Interferon-gamma release assays (IGRA) do not offer
      substantial improvements in sensitivity over the TST for the diagnosis of active
      disease. For latent TB infection, the IGRA correlates well with the exposure
      gradient and seems to have utility in reducing the number of children who undergo
      preventive therapy due to false-positive TST. Although IGRAs can be used as
      evidence of TB infection in children, appropriate specimen collection and
      microbiological confirmation of TB disease should remain a priority.

PMID- 21172671
TI  - Treatment of paediatric TB: revised WHO guidelines.
AB  - The World Health Organization has recently revised the recommended dosages of the
      main first-line anti-tuberculosis drugs for use in children. The recommended
      dosages and range of isoniazid, rifampicin, pyrazinamide and ethambutol have been
      increased from the previous recommended dosages. Ethambutol is now recommended
      for use in children of all ages including those of less than 5 years of age. This
      review explains the rationale for these recent revisions. Children require higher
      dosages than adults to achieve the same serum concentrations. Available data in
      HIV-uninfected children suggest that the revised dosages are within limits that
      have a very low risk of toxicity. An important challenge will be to examine the
      impact of higher dosages on clinical response, drug-drug interactions and risk of
      toxicity in HIV-infected children.

PMID- 21172670
TI  - New specimens and laboratory diagnostics for childhood pulmonary TB: progress and
      prospects.
AB  - Childhood pulmonary TB (PTB) is under diagnosed, in part due to difficulties in
      obtaining microbiological confirmation. However, given the poor specificity of
      clinical diagnosis, microbiological confirmation and drug susceptibility testing
      is important in guiding appropriate therapy especially in the context of drug
      resistant TB. Confirmation is often possible, even in infants and young children,
      if adequate specimens are collected. Culture yield varies with the severity of
      illness, specimen type and culture method. Induced sputum is recognised as a safe
      procedure with a high diagnostic yield. Advances include optimised protocols for
      smear microscopy and modified culture techniques, such as the Microscopic
      Observation Drug Susceptibility Assay. Detection of Mycobacterium tuberculosis
      nucleic acid in respiratory specimens has high specificity but relatively poor
      sensitivity, particularly for smear negative disease. The recent development of
      an integrated specimen processing and real-time PCR testing platform for M.
      tuberculosis and rifampicin resistance is an important advance that requires
      evaluation in childhood TB.

PMID- 21172672
TI  - Pleural tuberculosis in children.
AB  - Pleural tuberculosis effusion (PTE) in children is a diagnosis which must be
      considered in isolated pleural effusions in non-toxemic children. It is more
      common in children over 5 years of age. A history of close contact with an adult
      with pulmonary tuberculosis reinforces the suspicion for its diagnosis. Pleural
      effusion without any parenchymal lesion is the characteristic finding on the
      chest x-ray. However, in 20% to 40% of patients, intrathoracic disease may also
      occur. Adenosine deaminase, interferon-gamma, analysis of pleural fluid and
      pleural biopsy are the main tools for diagnostic confirmation. Tuberculin skin
      test may provide supporting evidence of tuberculous infection. PTE has a good
      prognosis in children and no long term sequelae are expected.

PMID- 21172673
TI  - Management of multidrug-resistant tuberculosis in children: a survival guide for
      paediatricians.
AB  - WHO estimated that of 9.4 million cases of tuberculosis (TB) worldwide in 2008,
      440,000 (3.6%) had multidrug-resistant (MDR)-TB. Childhood TB is estimated at 10
      15% of the total burden, but little is known about the burden of MDR-TB in
      children. Children in close contact with MDR-TB cases are likely to become
      infected with the same resistant strains and are vulnerable to develop disease.
      Although MDR-TB is a microbiological diagnosis, children should be treated
      empirically according to the drug susceptibility result of the likely source
      case, as often cultures cannot be obtained from the child. MDR-TB treatment in
      children is guided by the same principles, using the same second-line drugs as in
      adults, with careful monitoring for adverse effects. Co-infection with HIV poses
      particular challenges and requires early initiation of antiretroviral therapy.
      Preventive therapy for high-risk MDR-TB contacts is necessary, but no consensus
      guidance exists on how best to manage these cases. Pragmatic and effective
      Infection control measures are essential to limit the spread of MDR-TB.

PMID- 21172674
TI  - TB and HIV in children - advances in prevention and management.
AB  - The human immunodeficiency virus (HIV) epidemic has had a major impact on the age
      and gender profile of adult tuberculosis (TB) patients, resulting in increased
      exposure of HIV-infected and uninfected children at a very young age. Young
      and/or HIV-infected children are extremely vulnerable to develop severe forms of
      TB following recent exposure and infection. There is an urgent need to implement
      safe and pragmatic strategies to prevent TB in children, especially in TB endemic
      areas where they suffer the greatest burden of disease. The management of TB in
      HIV-infected children poses multiple challenges, but recent advances in the
      implementation of prevention of mother to child transmission (PMTCT) strategies
      and HIV care of infants offer hope. These include HIV testing and access to PMTCT
      for all pregnant women, routine testing of all HIV exposed infants and rapid
      initiation of antiretroviral treatment irrespective of clinical or immunological
      disease staging. In addition, careful scrutiny for TB exposure should occur at
      every health care visit, with provision of isoniazid preventive therapy (IPT)
      following each documented exposure event. Knowing the HIV infection status of
      child TB suspects is essential to optimize case management. Although multiple
      difficulties remain, recent advances demonstrate that the management of children
      with TB and/or HIV can be vastly improved by well focused interventions using
      readily available resources.

PMID- 21172675
TI  - Prospects for a new, safer and more effective TB vaccine.
AB  - Tuberculosis in infants and young children remains an all too common cause of
      morbidity and mortality in high burden countries, despite the fact that the
      majority of these children receive vaccination with BCG in infancy. BCG confers
      incomplete and variable protection against pulmonary tuberculosis [PTB] and is
      unsafe in HIV positive persons. Newer TB vaccines, which, it is hoped, will
      either replace or complement BCG are being developed and a number of these have
      reached the stage of clinical trials, with two booster vaccines going into Phase
      IIB trials in 2009. Prospects for at least one new licensed TB vaccine within the
      next 5-10 years appear reasonable. This article explores some of the issues
      around the development of new vaccines against TB and details the leading
      candidates.

PMID- 21172676
TI  - Pneumonia - management in the developing world.
AB  - Childhood pneumonias are an important cause of morbidity and mortality and
      annually contribute to over 2 million deaths among children under five years of
      age. To combat this, a standardized case management protocol developed by the
      World Health Organization has been adopted by the National programs in most high
      burden, resource constrained settings. This can detect patients with pneumonia
      early on and with ease at community level and also identify those who are at risk
      of dying due to a severe form of the disease if not referred or appropriately
      treated. However, as most deaths due to pneumonia occur in health facilities, it
      is equally important to standardise treatment at a facility level with pulse
      oximetry, regular monitoring for complications and the judicious use of
      antibiotics. The challenge is to identify other respiratory illnesses which mimic
      pneumonia resulting in under treatment with bronchodilators and over usage of
      antibiotics. This becomes particularly important in developing countries which
      have the dual burden of both the infectious and non-infectious illnesses. The
      strategy also needs refinement for diagnosing and treating pneumonia in severely
      under nourished and / or HIV co-infected children who are both at higher risk of
      disease as well as death due to it.

PMID- 21172677
TI  - Pneumonia in the developed world.
AB  - In this paper, we review the literature on the management of pneumonia in the
      developed world setting. Pneumonia is usually diagnosed on the basis of a cough,
      respiratory distress, a fever, and chest X-ray changes. Pneumonia affects all
      paediatric age groups, though the highest incidence is in the under 5s. There is
      a significant burden of primary and secondary care illness, although mortality is
      low. Inpatient admission rates for pneumonia may have increased in recent years
      in some regions. Pneumonia is unlikely if a child presents with solely wheeze. In
      routine clinical practice, a microbiological diagnosis is often not made, because
      current tests are insensitive. Aetiology varies with geographical location, but
      approximately half of cases are viral. The mainstay of management of moderate
      pneumonia (the commonest group presenting to secondary care) is careful
      assessment, and oral antibiotics, followed by early discharge when the patient
      shows signs of improvement. We summarise the available clinical trial data from
      the developed world; most of these trials are not adequately powered. Patients
      with moderately severe pneumonia do not require invasive investigation, but
      clinical judgement should be used to identify and investigate more complex cases.
      We discuss several pathogens that have gained importance as causal agents,
      including non-vaccinated strains of S. pneumoniae, Panton Valentine leucocidin S.
      aureus, H1N1 Influenza A and Human Bocavirus. The importance of antimicrobial
      resistance is considered, and we review recent data on long term effects of
      pneumonia in childhood. By reviewing the available literature, we demonstrate
      that there are clear evidence gaps, and we suggest future areas for clinical
      research.

PMID- 21172678
TI  - The management of pre-school wheeze.
AB  - Wheeze, a common symptom in pre-school children, is a continuous high-pitched
      sound, with a musical quality, emitting from the chest during expiration. A
      pragmatic clinical classification is episodic (viral) wheeze and multiple-trigger
      wheeze. Diagnostic difficulties include other conditions that give rise to noisy
      breathing which could be misinterpreted as wheeze. Most preschool children with
      wheeze do not need rigorous investigations. Primary prevention is not possible
      but avoidance of environmental tobacco smoke exposure should be strongly
      encouraged. Bronchodilators provide symptomatic relief in acute wheezy episodes
      but the evidence for using oral steroids is conflicting for children presenting
      to the Emergency Department [ED]. Parent initiated oral steroid courses cannot be
      recommended. High dose inhaled corticosteroids [ICS] used intermittently are
      effective in children with frequent episodes of moderately severe episodic
      (viral) wheeze or multiple-trigger wheeze, but this associated with short term
      effects on growth and cannot be recommended as a routine. Maintenance treatment
      with low to moderate continuous ICS in pure episodic (viral) wheeze is
      ineffective. Whilst low to moderate dose regular ICS work in multi-trigger
      wheeze, the medication does not modify the natural history of the condition. Even
      if there is a successful trial of treatment with ICS, a break in treatment should
      be given to see if the symptoms have resolved or continuous therapy is still
      required. Maintenance as well as intermittent Montelukast has a role in both
      episodic and multi trigger wheeze. Good multidisciplinary support and education
      is essential in managing this common condition.

PMID- 21172679
TI  - Asthma and chronic sickle cell lung disease: a dynamic relationship.
AB  - Chronic lung disease is a significant source of morbidity and mortality in
      patients with sickle cell disease. Asthma and sickle cell lung disease share many
      of the same clinical features and pathophysiological mechanisms. Though there is
      growing evidence of an association between sickle cell disease and airway hyper
      reactivity, there is still no consensus on the definition of asthma in sickle
      cell lung disease. This review will explore what we know about asthma and airway
      hyper-reactivity in sickle cell disease and whether currently available asthma
      therapies may be beneficial in delaying or averting the progression of sickle
      cell lung disease.

PMID- 21172680
TI  - Breathing abnormalities in children with breathlessness.
AB  - Dysfunctional breathing, hyperventilation and vocal cord dysfunction are
      frequently seen in children and adults. The prevalence is unknown. There are no
      standardized diagnostic criteria, and for now, effective exclusion of organic
      disease leaves the diagnosis of dysfunctional breathing. Therapy is mainly
      focussed on explanation of a benign condition and reassurance. Since
      dysfunctional breathing is a possible chronic condition, other therapies should
      be evaluated. In adults physiotherapy and breathing retraining appear beneficial.
      In childhood there is lack of evidence, and further research is necessary in
      order to optimise the outcome for children with dysfunctional breathing.

PMID- 21172681
TI  - How will accreditation of your ambulatory endoscopy center be an essential
      component of showing value-based health care?

PMID- 21172682
TI  - Neural plasticity, potential novel therapies that may enhance neural plasticity
      in the future, and the role these treatments may have in persons with neurologic
      injuries. Introduction.

PMID- 21172683
TI  - Neural plasticity: the biological substrate for neurorehabilitation.
AB  - Decades of basic science have clearly demonstrated the capacity of the central
      nervous system (CNS) to structurally and functionally adapt in response to
      experience. The field of neurorehabilitation has begun to use this body of work
      to develop neurobiologically informed therapies that harness the key behavioral
      and neural signals that drive neural plasticity. The present review describes how
      neural plasticity supports both learning in the intact CNS and functional
      improvement in the damaged or diseased CNS. A pragmatic, interdisciplinary
      definition of neural plasticity is presented that may be used by both clinical
      and basic scientists studying neurorehabilitation. Furthermore, a description of
      how neural plasticity may act to drive different neural strategies underlying
      functional improvement after CNS injury or disease is provided. The understanding
      of the relationship between these different neural strategies, mechanisms of
      neural plasticity, and changes in behavior may facilitate the development of
      novel, more effective rehabilitation interventions.

PMID- 21172684
TI  - Neural plasticity and locomotor recovery after spinal cord injury.
AB  - The discussion of neural plasticity and locomotor recovery after spinal cord
      injury (SCI) focuses on 2 main themes, the issues associated with detecting
      neural plasticity in human beings and the issue of how to translate information
      from animal models, in which neural plasticity can be more readily studied, to
      human clinical research and application. This article discusses the importance of
      studying neural plasticity to better understand the effects of current
      rehabilitation interventions and to devise the next generation of therapies. It
      reviews the current spectrum of clinical, functional, anatomical, and
      neurophysiological assessments of patients that can be made in
      neurorehabilitation and the relationship between those measures and the study of
      neural plasticity. Then the similarities and differences between animal models
      and human SCI are discussed in relation to the severity of injury, the effect of
      locomotor training on gait recovery, the localization of neural plasticity
      associated with that gait recovery, and the implications for interpreting the
      "translatability" of animal model data to human study and clinical practice. In
      summary, it is concluded that the study of neural plasticity and locomotor
      recovery after SCI is really in its infancy but that it is critical for the
      advancement of the science of neurorehabilitation and "restorative neurology."

PMID- 21172685
TI  - Genetic influences on neural plasticity.
AB  - Neural plasticity refers to the capability of the brain to alter function or
      structure in response to a range of events and is a crucial component of both
      functional recovery after injury and skill learning in healthy individuals. A
      number of factors influence neural plasticity and recovery of function after
      brain injury. The current review considers the impact of genetic factors.
      Polymorphisms in the human genes coding for brain-derived neurotrophic factor and
      apolipoprotein E have been studied in the context of plasticity and stroke
      recovery and are discussed here in detail. Several processes involved in
      plasticity and stroke recovery, such as depression or pharmacotherapy effects,
      are modulated by other genetic polymorphisms and are also discussed. Finally, new
      genetic polymorphisms that have not been studied in the context of stroke are
      proposed as new directions for study. A better understanding of genetic
      influences on recovery and response to therapy might allow improved treatment
      after a number of forms of central nervous system injury.

PMID- 21172686
TI  - Genetic factors modulating outcome after neurotrauma.
AB  - Wide variation in outcomes after neurotrauma, despite apparently similar injury
      severity, suggests that host factors may influence the recovery process.
      Genetically determined individual differences might be one such factor. The study
      of the genetic modulation of outcome after neurotrauma is at an early stage.
      Nevertheless, several important components of the response to neurotrauma can be
      identified in which genetic differences contribute to variability in outcome.
      These components include genetic modulators of pre- and postinjury cognitive
      reserve and behavioral homeostasis, and processes that modulate cytotoxic injury
      cascades (extent of injury) and injury repair. This work reviews what is known of
      the role of genetic variation in outcome after neurotrauma with a focus on
      clinical outcomes after traumatic brain injury. Polymorphisms reported to
      influence outcome after traumatic brain injury that illustrate important
      underlying mechanisms are emphasized.

PMID- 21172688
TI  - Cortical stimulation as an adjuvant to upper limb rehabilitation after stroke.
AB  - Recovery of upper limb function after stroke remains a clinical challenge in
      rehabilitation. New insights into the role of activity-dependent motor recovery
      have guided clinicians to develop novel task-oriented therapies that are
      effective in reducing functional limitations in hand use after stroke. A number
      of brain-stimulation techniques have been examined as therapeutic adjuvants
      applied to enhance functional outcomes. Cortical stimulation with the use of
      either noninvasive techniques or implanted technology has shown some promise as
      an adjuvant therapy but has yet to be supported in well-designed clinical trials.
      In this article, we review the physiology of neural plasticity and of cortical
      stimulation. Laboratory studies and early clinical trials of repetitive
      transcranial magnetic stimulation, transcranial direct current stimulation, and
      epidural cortical stimulation are reported. Cortical stimulation may have a role
      in facilitating motor recovery after stroke, but a better understanding of the
      physics of cortical stimulation, biological response to stimulation, effective
      stimulation protocols, and proper patient selection is needed.

PMID- 21172689
TI  - Exploring the potential for neural recovery after incomplete tetraplegia through
      nonsurgical interventions.
AB  - Persons with tetraplegia resulting from a cervical spinal cord injury believe
      that increasing upper limb (UL) function will improve their quality of life.
      Various lines of evidence demonstrate that persons with incomplete tetraplegia
      have the potential for improvements in both neural plasticity and function of the
      arms and hands. Therefore treatment to improve UL function in persons with
      incomplete tetraplegia should focus on improving motor control, not just
      compensation for the paralysis and sensory loss that follows a spinal cord
      injury. This article highlights the principles that underlie the facilitation of
      neural plasticity and functional changes: intensity, repeated practice,
      attention, and somatosensory augmentation. Evidence is presented for the
      application of these principles through the use of activity-based interventions
      in persons with tetraplegia and the hypothesis is proposed that the use of
      activity-based interventions will lead to greater, more beneficial neural
      plasticity as well as gains in UL function, in persons with incomplete
      tetraplegia.

PMID- 21172687
TI  - Assessment and modulation of neural plasticity in rehabilitation with
      transcranial magnetic stimulation.
AB  - Despite intensive efforts to improve outcomes after acquired brain injury,
      functional recovery is often limited. One reason for this limitation is the
      challenge in assessing and guiding plasticity after brain injury. In this
      context, transcranial magnetic stimulation (TMS), a noninvasive tool of brain
      stimulation, could play a major role. TMS has been shown to be a reliable tool
      for measuring plastic changes in the motor cortex associated with interventions
      in the motor system, such as motor training and motor cortex stimulation. In
      addition, as illustrated by the experience in promoting recovery from stroke, TMS
      is a promising therapeutic tool to minimize motor, speech, cognitive, and mood
      deficits. In this review, we will focus on stroke to discuss how TMS can provide
      insights into the mechanisms of neurologic recovery and how it can be used for
      measurement and modulation of plasticity after an acquired brain insult.

PMID- 21172690
TI  - Oscillating field stimulation in the treatment of spinal cord injury.
AB  - The application of electrical current to injured tissue is known to promote
      healing. The use of this modality in healing the injured spinal cord to promote
      neurologic recovery has been introduced as a potential treatment for patients who
      previously had minimal hope of recovery. In in vitro and in vivo experiments,
      neural regeneration has been seen to occur, especially when an oscillating field
      is used. With this modality, an electrical current is applied in which the
      polarity changes direction on a periodic basis, preventing the "die-back"
      phenomenon of severed neural pathways. This mechanism of recovery has been
      demonstrated in several species in which sacrifice has been undertaken and spinal
      cords examined. In a study of humans, a small number of patients participated in
      a single phase Ia trial in which the safety of an implantable device was
      demonstrated, with indications of probable benefit, consistent with laboratory
      and animal studies. In addition, a number of additional patients were treated,
      and their results were examined along with the original cohort and were compared
      with historical control subjects. The device used in this mode of treatment has
      not been approved for use in the general spinal cord-injured population, pending
      further study. A larger multi-institutional trial needs to be done to further
      demonstrate efficacy and effectiveness, and outcomes will need to be agreed upon
      by spinal cord injury researchers, patients, and regulators before widespread use
      will be permitted. Unfortunately, some subtle changes experienced and valued by
      patients are not recognized as important or desirable by regulators or by all
      researchers.

PMID- 21172692
TI  - Neural plasticity after acquired brain injury: evidence from functional
      neuroimaging.
AB  - The reorganization of the adult central nervous system after damage is a
      relatively new area of investigation. Neuroimaging methods, such as functional
      magnetic resonance imaging, diffusion tensor imaging, and positron emission
      tomography, have the ability to identify, in vivo, some of the processes involved
      in these neuroplastic changes and can help with diagnosis, prognosis, and
      potentially treatment approaches. In this article, traumatic brain injury and
      stroke are used as examples in which neural plasticity plays an important role in
      recovery. Basic concepts related to brain remodeling, including spontaneous
      reorganization and training-induced recovery, as well as characteristics of
      reorganization in successful recovery, are reviewed. The microscopic and
      molecular mechanisms that underlie neural plasticity and neurogenesis are briefly
      described. Finally, exciting future directions for the evaluation, diagnosis, and
      treatment of severe brain injury are explored, with an emphasis on how
      neuroimaging can help to inform these new approaches.

PMID- 21172693
TI  - Neural plasticity: future controversies?

PMID- 21172691
TI  - Role of low-level laser therapy in neurorehabilitation.
AB  - This year marks the 50th anniversary of the discovery of the laser. The
      development of lasers for medical use, which became known as low-level laser
      therapy (LLLT) or photobiomodulation, followed in 1967. In recent years, LLLT has
      become an increasingly mainstream modality, especially in the areas of physical
      medicine and rehabilitation. At first used mainly for wound healing and pain
      relief, the medical applications of LLLT have broadened to include diseases such
      as stroke, myocardial infarction, and degenerative or traumatic brain disorders.
      This review will cover the mechanisms of LLLT that operate both on a cellular and
      a tissue level. Mitochondria are thought to be the principal photoreceptors, and
      increased adenosine triphosphate, reactive oxygen species, intracellular calcium,
      and release of nitric oxide are the initial events. Activation of transcription
      factors then leads to expression of many protective, anti-apoptotic, anti
      oxidant, and pro-proliferation gene products. Animal studies and human clinical
      trials of LLLT for indications with relevance to neurology, such as stroke,
      traumatic brain injury, degenerative brain disease, spinal cord injury, and
      peripheral nerve regeneration, will be covered.

PMID- 21172694
TI  - Personality factors related to shift work tolerance in two- and three-shift
      workers.
AB  - This study aimed to investigate whether different personality variables were
      associated with shift work tolerance, and whether these potential associations
      were moderated by various types of shift work. The sample comprised 1505 nurses
      who worked either two or three rotating shifts. Personality traits were measured
      in terms of morningness, flexibility, languidity and hardiness. Morningness
      reflects the tendency to be alert relatively early in the morning and sleepy
      relatively early in the evening. Flexibility denotes the ability to both work and
      sleep at odd times of the day, while languidity concerns the tendency to become
      tired/sleepy when cutting down on sleep. Hardiness relates to resilience to
      stressful life events. The dependent variables in this study comprised of
      measures of insomnia, sleepiness, depression and anxiety. Hierarchical regression
      analyses, which controlled for demographic variables and work load, revealed that
      Morningness was significantly and negatively related to insomnia. The Morningness
      by Shift type interaction was overall significant for depressive symptoms.
      Morningness was near significantly associated with lower levels of depressive
      symptoms in three-shift workers, but unrelated to depressive symptoms in two
      shift workers. Flexibility was associated with higher levels of depressive
      symptoms. Flexibility by Shift type interaction was significant for insomnia,
      indicating that flexibility was negatively associated with insomnia for three
      shift workers and unrelated with insomnia for two-shift workers. Languidity was
      associated with higher levels of sleepiness, depressive and anxiety symptoms.
      Hardiness was associated with lower levels of all four dependent variables.

PMID- 21172695
TI  - Design and characterization of novel beta-cyclodextrin based copolymer materials.
AB  - Reported herein are the systematic design and characterization of several novel
      polyurethane (PU) copolymers containing a macrocyclic porogen (beta-cyclodextrin;
      beta-CD). These copolymers were synthesized from the reaction between beta-CD
      with different types of diisocyanate linker molecules (e.g., 1,6-hexamethylene
      diisocyanate (HDI), 4,4'-dicyclohexylmethane diisocyanate (CDI), 4,4'
      diphenylmethane diisocyanate (MDI), 1,4-phenylene diisocyanate (PDI) and 1,5
      naphthalene diisocyanate (NDI)) at variable synthetic conditions. The copolymers
      were characterized using diffuse reflectance infrared Fourier transform
      spectroscopy (DRIFTS), solid state (13)C CP-MAS NMR, (1)H/(13)C solution NMR
      spectroscopy, thermogravimetric analysis (TGA) and elemental analyses (CHN). The
      PU copolymers were generally insoluble in water and the optimal preparation of
      copolymer materials for sorption-based applications is for beta-CD/linker
      synthetic mole ratios from 1:1 to 1:3. The practical upper limit of the crosslink
      density (approximately 1:7, beta-CD/linker) depends on the steric bulk of the
      cross linker units.

PMID- 21172697
TI  - Second order inverse response process identification from transient step
      response.
AB  - Simple algorithms for identification of inverse response models from step
      response are difficult to obtain because analytically the solution of a system of
      coupled nonlinear equations is required. In this article we propose a simple
      identification procedure for second order inverse response processes, based on
      the plant step response. The algorithm provides the model parameters in a
      sequential way, thus avoiding the solution of a nonlinear equation system.
      Moreover the algorithm is flexible because it can be suited to user requirements,
      thus modifying the algorithm performance. Finally error bounds on the identified
      parameters are provided which are useful if the model is used for control design
      purposes.

PMID- 21172696
TI  - Outdoor temperature is associated with serum HDL and LDL.
AB  - BACKGROUND: While exposures to high and low air temperatures are associated with
      cardiovascular mortality, the underlying mechanisms are poorly understood. The
      risk factors for cardiovascular disease include high levels of total cholesterol
      and low-density lipoprotein (LDL), and low levels of high-density lipoprotein
      (HDL). We investigated whether temperature was associated with changes in
      circulating lipid levels, and whether this might explain part of the association
      with increased cardiovascular events. METHODS: The study cohort consisted of 478
      men in the greater Boston area with a mean age of 74.2 years. They visited the
      clinic every 3-5 years between 1995 and 2008 for physical examination and to
      complete questionnaires. We excluded from analyses all men taking statin
      medication and all days with missing data, resulting in a total of 862 visits.
      Associations between three temperature variables (ambient, apparent, and dew
      point temperature) and serum lipid levels (total cholesterol, HDL, LDL, and
      triglycerides) were studied with linear mixed models that included possible
      confounders such as air pollution and a random intercept for each subject.
      RESULTS: We found that HDL decreased -1.76% (95% CI: from -3.17 to -0.32, lag 2
      days), and -5.58% (95% CI: from -8.87 to -2.16, moving average of 4 weeks) for
      each 5 degrees C increase in mean ambient temperature. For the same increase in
      mean ambient temperature, LDL increased by 1.74% (95% CI: 0.07-3.44, lag 1 day)
      and 1.87% (95% CI: 0.14-3.63, lag 2 days). These results were also similar for
      apparent and dew point temperatures. No changes were found in total cholesterol
      or triglycerides in relation to temperature increase. CONCLUSIONS: Changes in HDL
      and LDL levels associated with an increase in ambient temperature may be among
      the underlying mechanisms of temperature-related cardiovascular mortality.

PMID- 21172698
TI  - Capillary-pressure driven adhesion of rigid-planar surfaces.
AB  - A thin film of viscous-Newtonian fluid sandwiched between parallel-plane walls,
      is examined both experimentally and theoretically for gap spacings initially much
      smaller than the capillary length to determine the conditions for adhesion. The
      problem is parameterized by the variables F, which is the ratio of an external
      load generated by one of the parallel-plane surfaces, to the product of surface
      tension and a characteristic length scale, and the static contact angle alpha. An
      analytical solution for the change in gap height as a function of elapsed time is
      derived in the limit of small Reynolds and zero capillary numbers. The load is
      suspended for a long but finite elapsed time as the gap spacing approaches a
      critical value, and for gap spacing values less than the critical one the load is
      suspended indefinitely. Experiments are performed with typical elapsed times of
      O(100-1000s) using fluids with viscosity, O(1000 cSt), but different surface
      tension and contact angle for gap spacings O(10-100MUm) with loads of either 2.7N
      or 4.9N. There is good agreement between the theory and experiments.

PMID- 21172699
TI  - Editorial comment.

PMID- 21172700
TI  - Initial pre-scrotal approach for palpable cryptorchid testis: results during a 3
      year period.
AB  - PURPOSE: Pre-scrotal orchiopexy is emerging as an alternative approach for
      cryptorchid testes that can be preoperatively mobilized into the scrotum. We
      present our 3-year pre-scrotal orchiopexy series for all palpable cryptorchid
      testes regardless of their mobility into the scrotum preoperatively. MATERIALS
      AND METHODS: We retrospectively reviewed all patients who underwent pre-scrotal
      orchiopexy during a 3-year period. Data collected included preoperative and
      postoperative testicular position, mobility of the testis into the scrotum
      preoperatively or with the patient under general anesthesia, patency of processus
      vaginalis, operative times and complications. RESULTS: A total of 88 cryptorchid
      testes were treated using single pre-scrotal incision orchiopexy. Mean patient
      age was 4.9 years. Of the testes 74 (84.1%) could be milked down to the scrotum
      preoperatively and 14 (15.9%) could not. Of the 14 immobile testes 8 were
      intracanalicular and 6 were in the superficial inguinal pouch. Pre-scrotal
      orchiopexy was successful in all 74 testes that were mobilized into the scrotum
      preoperatively. However, 6 of 14 testes (43%) that could not be moved to the
      scrotum were effectively managed by a single pre-scrotal incision, while 8 (57%)
      required an additional groin incision for successful orchiopexy. No complications
      were observed during a mean followup of 7.1 months. CONCLUSIONS: Orchiopexy using
      a pre-scrotal approach is a viable alternative for palpable cryptorchid testes
      that can be preoperatively mobilized into the scrotum. Cryptorchid testes that
      are palpable but cannot be moved to the scrotum can be managed by the pre-scrotal
      approach alone in 40% of cases or with an additional groin incision in 60%.

PMID- 21172701
TI  - Meatotomy using local anesthesia and sedation or general anesthesia with or
      without penile block in children: a prospective randomized study.
AB  - PURPOSE: Meatotomy is a simple, common procedure for the treatment of meatal
      stenosis. We compared the outcomes of meatotomy performed using local anesthesia
      and sedation, and general anesthesia with and without penile block. MATERIALS AND
      METHODS: A prospective comparative design was used. Participants included 76 boys
      1.5 to 10 years old treated for meatal stenosis at a tertiary, university
      affiliated, pediatric medical center in 2008. Children were randomly allocated to
      undergo surgery with sedation and local anesthesia, or general anesthesia with or
      without penile block. All procedures were performed with the same method by the
      same surgeon. For local anesthesia EMLA 5% cream (lidocaine 2.5% and prilocaine
      2.5%) covered with an occlusive dressing was applied 1 hour preoperatively, and
      midazolam (in patients younger than 5 years) or nitrous oxide (older than 5
      years) was used for sedation. General anesthesia was induced with inhaled
      sevoflurane, and ropivacaine was used for dorsal penile nerve block. RESULTS:
      There was no difference among the groups in pain level intraoperatively (no pain
      in 92% to 93% of patients), 24 hours postoperatively (no pain in 81% to 88%) or
      after 1 month, or in complication rates (bleeding in 3 patients, laryngospasm in
      2). General anesthesia with penile block was associated with a trend of less
      dysuria. Quality of void was excellent in 87% of patients at 24 hours and in 70%
      at 1 month, and parental satisfaction was high (88% to 92%). CONCLUSIONS:
      Meatotomy performed using local anesthesia and sedation has an equally good
      outcome to meatotomy performed using general anesthesia with or without penile
      block.

PMID- 21172702
TI  - Re: A novel pull-through technique for the surgical management of idiopathic
      hydrocele. S. Y. Onol, Y. O. Ilbey, F. F. Onol, E. Ozbek, B. Arslan and A. Akbas.
      J Urol 2009; 181: 1201-1205.

PMID- 21172703
TI  - Editorial comment.

PMID- 21172705
TI  - Use of internal stent, external transanastomotic stent or no stent during
      pediatric pyeloplasty: a decision tree cost-effectiveness analysis.
AB  - PURPOSE: Copious studies exist regarding the use of stents in pediatric
      pyeloplasty. Most surgeons use either no stent, an internal (Double-J(r)) stent
      or an external transanastomotic pyeloureteral stent. We propose the first known
      study to compare all 3 methods using a decision tree model that incorporates
      success rates, complications, patient discomfort and costs. MATERIALS AND
      METHODS: We created a deterministic decision tree model. We conducted a
      literature search querying urinary diversion in pediatric pyeloplasty. We used
      the largest studies for base inputs and remaining studies for sensitivity
      analysis. Direct costs from actual patients seen at the University of California
      San Francisco populated cost inputs. RESULTS: Total quality adjusted life-years
      during a 16-year period for no stents was 12.70851 with a total cost of $6,122.
      Total quality adjusted life-years for external stents was 12.71098 at a total
      cost of $5,702. Internal stents resulted in total quality adjusted life-years of
      12.69983 and cost of $8,421. Thus, external stents dominated no stents and
      internal stents, while no stents dominated internal stents. On sensitivity
      analysis even decreasing complication and failure rates of internal stents to
      zero did not make them cost effective due to the costs associated with stent
      removal. In contrast, decreasing complication and pyeloplasty rates of no stents
      by 20% resulted in an incremental cost-effectiveness ratio of $5,475 per quality
      adjusted life-year gained compared to external stents. CONCLUSIONS: External and
      no stents are superior to internal stents. Given high overall success rates of
      pyeloplasty regardless of stent method, perhaps more attention should be given to
      cost from a health policy standpoint.

PMID- 21172706
TI  - Editorial comment.

PMID- 21172707
TI  - Primary cutaneous T cell lymphoma of the external genitalia.

PMID- 21172708
TI  - Ectopic ureter in an adolescent female presenting with primary nocturnal enuresis
      and new onset urinary incontinence.

PMID- 21172711
TI  - Editorial comment.

PMID- 21172712
TI  - Assessment of parental satisfaction in children undergoing voiding
      cystourethrography without sedation.
AB  - PURPOSE: Approximately 50,000 children undergo voiding cystourethrography
      annually. There is a recent trend toward using sedation or delaying voiding
      cystourethrography due to the anticipated distress to the patient. We
      hypothesized that with adequate preparation and proper techniques to minimize
      anxiety, voiding cystourethrography can be performed without sedation. We
      assessed parental satisfaction associated with patient and parent experience of
      voiding cystourethrography without sedation. MATERIALS AND METHODS: We used a 33
      question survey to evaluate parental satisfaction with patient and parent
      experience of voiding cystourethrography without sedation. Children were divided
      into 3 groups according to toilet training status. Statistical analysis was
      performed using Stata(r). RESULTS: A total of 200 surveys were completed. Of the
      children 54% were not toilet trained. Of the parents 90% reported adequate
      preparation. More than half of parents classified the experience of voiding
      cystourethrography as equivalent to or better than a physical examination,
      immunization, ultrasound and prior catheterization. Most parents were satisfied
      with the ability of the child to tolerate the procedure and considered the
      experience better than expected. Children in the process of toilet training had
      the most difficulty with the procedure, correlating with lower levels of parental
      satisfaction. CONCLUSIONS: Voiding cystourethrography performed with adequate
      preparation and support can be tolerated without sedation. Children in the
      process of toilet training and females tolerate the procedure least.

PMID- 21172714
TI  - Lower urinary tract conditions in children with attention deficit hyperactivity
      disorder: correlation of symptoms based on validated scoring systems.
AB  - PURPOSE: We investigated whether certain voiding problems have a higher incidence
      in patients with attention deficit disorder with hyperactivity compared to age
      matched controls. MATERIALS AND METHODS: We used the Conners Parent Rating Scale
      revised for attention deficit disorder with hyperactivity and lower urinary tract
      symptom score to evaluate voiding problems. A total of 62 children with attention
      deficit disorder and 124 healthy controls were enrolled. We evaluated
      uroflowmetry patterns in both groups. Residual urine volumes and Bristol stool
      scale were noted. We examined the correlation between total Conners Parent Rating
      Scale-revised and lower urinary tract symptom score in patients with attention
      deficit disorder. Additionally we analyzed each index of the Conners Parent
      Rating Scale-revised separately in terms of correlation with symptom subgroups
      for lower urinary tract symptom scores. RESULTS: Mean +/- SD total lower urinary
      tract symptom score was 11.1 +/- 2.9 in patients with attention deficit disorder
      with hyperactivity and 3.2 +/- 1.3 in controls, a difference that was
      statistically significantly (p <0.001). With the exception of constipation, mean
      scores of all lower urinary tract symptom subindices were significantly higher in
      patients with attention deficit disorder compared to controls. Symptoms evaluated
      in lower urinary tract symptom score were mostly correlated with attention
      deficit disorder index of the Conners Parent Rating Scale-revised. If a child
      with attention deficit disorder has a high index in the Conners Parent Rating
      Scale-revised, he or she is more likely to have urgency. Also, if a child with
      attention deficit disorder has a high hyperactivity subscale score, he or she is
      more likely to have enuresis. CONCLUSIONS: Voiding problems are more common in
      children with attention deficit disorder with hyperactivity than in age matched
      controls. Urgency and enuresis are the outstanding problems in children with
      attention deficit disorder. Simultaneous use of the Conners Parent Rating Scale
      revised and lower urinary tract symptom score questionnaire should be encouraged
      in patients with attention deficit disorder to allow a structured and
      quantitative evaluation of these overlapping problems.

PMID- 21172715
TI  - Editorial comment.

PMID- 21172716
TI  - Re: Magnetic resonance urethrography to assess obliterative posterior urethral
      stricture: comparison to conventional retrograde urethrography with voiding
      cystourethrography. M. M. Oh, M. H. Jin, D. J. Sung, D. K. Yoon, J. J. Kim and D.
      G. Moon. J Urol 2010; 183: 603-607.

PMID- 21172718
TI  - A comparative study of toxicity identification using Daphnia magna and Tigriopus
      japonicus: implications of establishing effluent discharge limits in Korea.
AB  - In Korea, the new permission criteria for industrial effluents based on Daphnia
      magna acute toxicity tests will be gradually implemented starting from 2011.
      Thus, in this study, toxicity assessment and identification using a marine
      species (Tigriopus japonicus) and the freshwater species (D. magna) was
      comparatively investigated. Effluent from an acid mine drainage treatment plant
      showed acute toxicity toward both organisms due to low pH, which was removed by
      neutralization of the effluent. Additionally, evaluation of the effluent of an
      electronics company revealed that Cu was attributable to the observed toxicity,
      and the effluent was more toxic toward T. japonicus than D. magna. Moreover,
      effluents from a metal plating factory were acutely toxic toward D. magna (6.50
      TU), while they were not toxic against T. japonicus. Toxicity identification
      revealed that the high level of Cl- (12,841 mg L(-1)) was the cause of toxicity.
      Thus, the effluents had no effect on the marine species, T. japonicus. These
      findings suggest that a marine species rather than a freshwater species is more
      desirable for toxicity assessment of industrial effluent discharged into the
      saltwater, and thus should be considered in the legislation of toxicity-based
      discharge limits in Korea.

PMID- 21172719
TI  - Modeling high adsorption capacity and kinetics of organic macromolecules on super
      powdered activated carbon.
AB  - The capacity to adsorb natural organic matter (NOM) and polystyrene sulfonates
      (PSSs) on small particle-size activated carbon (super-powdered activated carbon,
      SPAC) is higher than that on larger particle-size activated carbon (powdered
      activated carbon, PAC). Increased adsorption capacity is likely attributable to
      the larger external surface area because the NOM and PSS molecules do not
      completely penetrate the adsorbent particle; they preferentially adsorb near the
      outer surface of the particle. In this study, we propose a new isotherm equation,
      the Shell Adsorption Model (SAM), to explain the higher adsorption capacity on
      smaller adsorbent particles and to describe quantitatively adsorption isotherms
      of activated carbons of different particle sizes: PAC and SPAC. The SAM was
      verified with the experimental data of PSS adsorption kinetics as well as
      equilibrium. SAM successfully characterized PSS adsorption isotherm data for
      SPACs and PAC simultaneously with the same model parameters. When SAM was
      incorporated into an adsorption kinetic model, kinetic decay curves for PSSs
      adsorbing onto activated carbons of different particle sizes could be
      simultaneously described with a single kinetics parameter value. On the other
      hand, when SAM was not incorporated into such an adsorption kinetic model and
      instead isotherms were described by the Freundlich model, the kinetic decay
      curves were not well described. The success of the SAM further supports the
      adsorption mechanism of PSSs preferentially adsorbing near the outer surface of
      activated carbon particles.

PMID- 21172720
TI  - The effect of physiologically relevant dynamic shear stress on platelet and
      endothelial cell activation.
AB  - INTRODUCTION: Blood flow induced shear stress plays an important role in platelet
      and endothelial cell functions. The goal of this study was to investigate the
      effect of physiologically relevant dynamic shear stress on platelet and
      endothelial cells. MATERIALS AND METHODS: Pulsatile shear stress waveforms
      mimicking the flow in a normal left coronary artery (0.1-1 Pa), at a 60% stenosis
      (0.2 - 6 Pa) and in the recirculation zone (0.01 - 0.5 Pa) behind a stenosis were
      used to stimulate platelets and endothelial cells in a cone and plate shearing
      device. Platelet activation was measured by CD62P expression and thrombogenicity.
      Meanwhile, endothelial cell activation and damage was measured by cell surface
      ICAM-1 and tissue factor expression using fluorescence microscopy. Endothelial
      tissue factor activity was measured using a commercial kit. RESULTS: Results
      showed that for platelets, a short exposure to elevated shear stress at the
      stenosis throat did not induce significant increase in platelet activation or
      thrombogenicity. While the low pulsatile shear stress had a potential for
      enhanced thrombosis. Both low and high pulsatile shear stress led to a
      significant increase in ICAM-1 expression on endothelial cell surface, but only
      low shear stress caused tissue factor over expression and enhanced tissue factor
      activity. CONCLUSION: These results suggest that low pulsatile shear stress may
      be more atherogenic, compared to elevated shear stress induced by stenosis.

PMID- 21172721
TI  - Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic
      embolism in patients with non-valvular atrial fibrillation: a Phase II study of
      AZD0837 in patients who are appropriate for but unable or unwilling to take
      vitamin K antagonist therapy.
AB  - BACKGROUND: Some patients with atrial fibrillation (AF) cannot be treated with
      vitamin K antagonists (VKAs) and will therefore not receive effective
      thromboprophylaxis. The primary objective of the present Phase II trial
      (NCT00623779) was to assess the feasibility of conducting a study with a novel
      oral anticoagulant, the direct thrombin inhibitor AZD0837, in patients with AF
      unable or unwilling to take warfarin, by evaluation of dropout rates and
      compliance. METHODS: Patients were randomised to receive AZD0837 extended-release
      tablets 150 mg (n=43) or 300 mg (n = 42) once daily, or standard therapy (no
      treatment, aspirin 75-325 mg or clopidogrel 75 mg once daily; n = 46) for a
      median treatment duration of 6 weeks. RESULTS: Reasons for patients not being
      treated with warfarin were: refusal or permanent cessation decided by the patient
      (64.8%), inability to keep international normalised ratio 2-3 over a 3-month
      period (23.2%), physician assessment that VKA was inappropriate (20.4%) and
      warfarin allergy (2.8%). Compliance with treatment (mean +/- SD) was 97.0 +/-
      16.5% for AZD0837 150 mg and 99.8 +/- 1.4% for 300 mg. Compliance with study
      visits was high (mean 93-98%). The numbers of dropouts were four, six and three,
      whilst minor or clinically significant minor bleeds were reported in zero, five
      and two patients in the AZD0837 150 mg, 300 mg and standard-therapy groups,
      respectively. No major bleeds were reported. Both doses of AZD0837 reduced levels
      of fibrin D-dimer and prolonged activated partial thromboplastin time, ecarin
      clotting time and thrombin clotting time. CONCLUSIONS: AZD0837 had a good safety
      profile during this study, including a low incidence of bleeding events, with
      effective anticoagulation on pharmacodynamic parameters. A larger study in AF
      patients unable or unwilling to take warfarin is feasible, as judged by
      compliance and dropout rates.

PMID- 21172722
TI  - Thrombophilic screening in young patients (< 40 years) with idiopathic ischemic
      stroke: a controlled study.
AB  - INTRODUCTION: Despite extensive clinical and laboratory investigations, the
      etiology of ischemic stroke remains unknown in approximately one third of
      patients. MATERIALS AND METHODS: Thirty-four consecutive patients less than 40
      years old (Males 13, Females 21, mean age 26.6 years, range 2-39) with documented
      ischemic stroke underwent, one year after the acute event, laboratory evaluation
      of antithrombin, protein C, free and total protein S, activated protein C
      resistance, fibrinogen, factor VII:C, homocysteine levels and antiphospholipid
      antibodies (APA). Moreover, prevalence of F5 R506Q, F2 G2021A and homozygosis for
      thermolabile variant C677T of the methylenetetrahydrofolate reductase (MTHFR)
      were also evaluated and compared to the results obtained in 120 normal controls.
      RESULTS: Antithrombin and protein C levels resulted normal in all cases. One
      patient (2.9%) showed free protein S deficiency and 3 patients (8.8%) had
      activated protein C resistance. Homocysteine levels above 15 MUmol/L were found
      in one patient (2.9%). APA were found in 21 patients (61.7%) and in only 2 out of
      120 (1.66%) controls (OR=95.31; 95% C.I.: 18.22-667.81). The multivariate
      analysis selected that the presence of APA was significantly associated with an
      increased risk of stroke (OR=156.60; 95% C.I.: 25.99-943.47) in this cohort of
      patients. The combination between APA and cardiovascular risk factors determined
      a risk of 29-fold (OR=29.31; 95% CI: 3.28-261.69). DISCUSSION: Our data suggest
      that the presence of APA is associated with an increased risk of idiopathic
      ischemic stroke in young patients. Furthermore, also the combination of APA and
      cardiovascular risk factors is significantly associated with development of
      idiopathic ischemic stroke.

PMID- 21172723
TI  - Anticoagulant and anti-platelet activity of polyphenolic-polysaccharide
      preparation isolated from the medicinal plant Erigeron canadensis L.
AB  - The polyphenolic-polysaccharide preparation from Erigeron canadensis L. was
      isolated by multi-step process, characterized by chromatographic and
      spectroscopic methods, and was subjected to anion-exchange chromatography. The
      whole preparation demonstrated in vivo anticoagulant activity, and the effect was
      neutralized by protamine sulfate. It had also anti-platelet activity, limited to
      the cyclooxygenase pathway, induced by arachidonic acid. The plant preparation
      was fractionated to receive the fraction of the highest anticoagulant activity -
      7-9IU/mg of heparin standard, expressed in aPTT. The influences of the plant
      preparation as well as its the most active fraction on thrombin and factor Xa
      inactivation by antithrombin, and on thrombin inhibition by heparin cofactor II,
      were compared. The both tested plant preparations inhibited thrombin as well as
      factor Xa amidolytic activities in the presence of antithrombin, but much higher
      concentrations were required to obtain the same effects like for unfractionated
      heparin. The mechanisms of anticoagulant activity in the case of the plant
      preparation are based on interactions with heparin cofactor II, to inactivate
      thrombin. Chromatographic and spectroscopic methods revealed its macromolecular
      polyanionic non-sulfated polyphenolic-polysaccharide conjugate, with carboxylic
      groups. The polysaccharide part constituted 32% of the total mass and was
      homogenous, with molecular mass 38kDa, containing mainly hexuronic acids, and
      much smaller amounts of glucose, arabinose, galactose, as well as some traces of
      mannose, xylose and rhamnose. Polyphenolic part, with molecular mass >12.5kDa,
      was rich in hydroxylic rests as well as in carboxylic groups, free and
      esterified. The polyphenolic-polysaccharide preparation from E. canadensis may
      become a new source of anticoagulant compound potentially useful in anticoagulant
      and anti-platelet therapy.

PMID- 21172724
TI  - WITHDRAWN: Oxidative stress-induced apoptosis is mediated by calpains in
      alcoholic cardiomyopathy.
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- 21172725
TI  - Direct coupling of a genome-scale microbial in silico model and a groundwater
      reactive transport model.
AB  - The activity of microorganisms often plays an important role in dynamic natural
      attenuation or engineered bioremediation of subsurface contaminants, such as
      chlorinated solvents, metals, and radionuclides. To evaluate and/or design
      bioremediated systems, quantitative reactive transport models are needed. State
      of-the-art reactive transport models often ignore the microbial effects or
      simulate the microbial effects with static growth yield and constant reaction
      rate parameters over simulated conditions, while in reality microorganisms can
      dynamically modify their functionality (such as utilization of alternative
      respiratory pathways) in response to spatial and temporal variations in
      environmental conditions. Constraint-based genome-scale microbial in silico
      models, using genomic data and multiple-pathway reaction networks, have been
      shown to be able to simulate transient metabolism of some well studied
      microorganisms and identify growth rate, substrate uptake rates, and byproduct
      rates under different growth conditions. These rates can be identified and used
      to replace specific microbially-mediated reaction rates in a reactive transport
      model using local geochemical conditions as constraints. We previously
      demonstrated the potential utility of integrating a constraint-based microbial
      metabolism model with a reactive transport simulator as applied to bioremediation
      of uranium in groundwater. However, that work relied on an indirect coupling
      approach that was effective for initial demonstration but may not be extensible
      to more complex problems that are of significant interest (e.g., communities of
      microbial species and multiple constraining variables). Here, we extend that work
      by presenting and demonstrating a method of directly integrating a reactive
      transport model (FORTRAN code) with constraint-based in silico models solved with
      IBM ILOG CPLEX linear optimizer base system (C library). The models were
      integrated with BABEL, a language interoperability tool. The modeling system is
      designed in such a way that constraint-based models targeting different
      microorganisms or competing organism communities can be easily plugged into the
      system. Constraint-based modeling is very costly given the size of a genome-scale
      reaction network. To save computation time, a binary tree is traversed to examine
      the concentration and solution pool generated during the simulation in order to
      decide whether the constraint-based model should be called. We also show
      preliminary results from the integrated model including a comparison of the
      direct and indirect coupling approaches and evaluated the ability of the approach
      to simulate field experiment.

PMID- 21172726
TI  - Synthesis and biological activity of 7H-benzo[4,5]indolo[2,3-b]-quinoxaline
      derivatives.
AB  - New 7-(2-aminoethyl)-7H-benzo[4,5]indolo[2,3-b]quinoxalines (13-20) were
      synthesized with high yields starting from 3H-benzo[e]indole-1,2-dione. These
      compounds were screened for the cytotoxicity, anti-viral activity, interferon
      inducing ability and DNA affinity compared with the corresponding 6-(2
      aminoethyl)-6H-indolo[2,3-b]quinoxaline derivatives (1-12). It was shown, that
      compounds 13-20 bind to DNA stronger (lg Ka=6.23-6.87) than compounds 1-12 (lg
      Ka=5.57-5.89). Anti-viral activity is significantly reduced with annulations of
      benzene ring in Indoloquinoxaline moiety 13-20.

PMID- 21172727
TI  - Persistent operational synchrony within brain default-mode network and self
      processing operations in healthy subjects.
AB  - Based on the theoretical analysis of self-consciousness concepts, we hypothesized
      that the spatio-temporal pattern of functional connectivity within the default
      mode network (DMN) should persist unchanged across a variety of different
      cognitive tasks or acts, thus being task-unrelated. This supposition is in
      contrast with current understanding that DMN activated when the subjects are
      resting and deactivated during any attention-demanding cognitive tasks. To test
      our proposal, we used, in retrospect, the results from our two early studies
      (Fingelkurts, 1998; Fingelkurts et al., 2003). In both studies for the majority
      of experimental trails we indeed found a constellation of operationally
      synchronized cortical areas (indexed as DMN) that was persistent across all
      studied experimental conditions in all subjects. Furthermore, we found three
      major elements comprising this DMN: two symmetrical occipito-parieto-temporal and
      one frontal spatio-temporal patterns. This new data directly supports the notion
      that DMN has a specific functional connotation - it provides neurophysiologic
      basis for self-processing operations, namely first-person perspective taking and
      an experience of agency.

PMID- 21172728
TI  - Possible role of EBV in breast cancer and other unusually EBV-associated cancers.
AB  - Epstein-Barr virus (EBV) a ubiquitous gamma herpesvirus persists for life,
      generally without health consequences. However, it is associated with several
      well-recognized malignancies, such as Burkitt's lymphoma and nasopharyngeal
      carcinoma. A growing list of malignancies has been proposed to be EBV-associated:
      most of which are consistently EBV-positive whereas others show inconsistent
      results. The possible contribution of EBV to the development and/or progression
      of different "non-classical" tumors is discussed in terms of putative "non
      traditional'' infection in EBV-related tumors.

PMID- 21172729
TI  - Laser assisted atom probe analysis of thin film on insulating substrate.
AB  - We demonstrate that the atom probe analyses of metallic thin films on insulating
      substrates are possible using laser assisted field evaporation. The tips with
      metallic thin film and insulating substrate (0.6-3 MUm in thickness) were
      prepared by the lift-out and annular ion beam milling techniques on tungsten
      supports. In spite of the existence of thick insulating layer between the
      metallic film and the tungsten support, atom probe tomography with practical mass
      resolution, signal-to-noise ratio and spatial resolution was found to be possible
      using laser assisted field evaporation.

PMID- 21172730
TI  - Implementation of targeted interventions to control Escherichia coli O157:H7 in a
      commercial abattoir.
AB  - The objective of this study was to define locations on the carcass with highest
      contamination of E. coli O157 throughout the harvest process and implement
      targeted interventions to reduce or eliminate contamination. To establish a
      pathogen baseline, samples were collected at the foreshank, hindshank, inside
      round, neck and midline area and evaluated for E. coli O157:H7 presence.
      Environmental samples were also collected in the harvest area and the fabrication
      area of the facility. E. coli O157:H7 prevalence was highest on the foreshank,
      hindshank and inside rounds in the baseline study and steam vacuums/cones were
      implemented as an intervention in these specific areas on the harvest floor. At
      pre-evisceration, foreshank prevalence of E. coli O157:H7 was significantly
      (P<0.05) reduced from 21.7% to 3.1% after the application of steam interventions.
      At the final rail, foreshank prevalence in the baseline study was 4.2% while no
      E. coli O157:H7 was detected post-intervention implementation. E. coli O157:H7 on
      hindshanks and inside rounds was significantly reduced after intervention
      implementation from 24.2 to 11.5% and 37.5 to 16.7%, respectively at the final
      rail. Pathogen contamination of environmental samples collected in fabrication
      declined from 6.7% to 0.7% after slaughter interventions were implemented. Data
      indicate the identifying areas of contamination on the carcass and implementing
      interventions can significantly reduce E. coli O157 on the carcasses and in the
      fabrication environment.

PMID- 21172731
TI  - The effects of high pressure processing on pork quality, palatability, and
      further processed products.
AB  - The objective was to evaluate high pressure processing (HPP) on postmortem
      metabolism and pork quality. Six pigs were randomly selected immediately after
      slaughter. After splitting, one side was randomly designated for HPP of 215 MPa
      for 15 s with water temperature at 33  degrees C and the other side (non-pressure
      treated) served as the control. Chilled sides were fabricated into loins,
      boneless picnic, boneless Boston butt, and ham. Samples were cut from the loin,
      inside portion of the ham and cushion (M. triceps brachii). Pork quality, lipid
      oxidation, connective tissue solubility, protein functionality, sensory analysis,
      and processed characteristics of restructured hams were evaluated. HPP partially
      inhibits postmortem metabolism, indicated by lower muscle lactate levels and
      higher ultimate pH values. Cook and drip loss were both reduced in HPP treated
      muscles compared to controls. HPP treated sides were more tender than controls.
      Collagen content was not different between HPP and control groups.

PMID- 21172732
TI  - Characterization of composites based on expanded polystyrene wastes and wood
      flour.
AB  - This paper aims to evaluate the potential for the use of recycled expanded
      polystyrene and wood flour as materials for the development of wood plastic
      composites. The effects of wood flour loading and coupling agent addition on the
      mechanical properties and morphology of wood thermoplastic composites were
      examined. In addition, a methodology for the thermo-mechanical recycling of
      expanded polystyrene waste was developed. The results show that the mechanical
      properties decreased as the wood flour loading increased. On the other hand, the
      use of poly(styrene-co-maleic anhydride), SMA, as a coupling agent improved the
      compatibility between the wood flour and polystyrene matrix and the mechanical
      properties subsequently improved. A morphological study revealed the positive
      effect of the coupling agent on the interfacial bonding. The density values
      obtained for the composites were compared with the theoretical values and showed
      agreement with the rule of mixtures. Based on the findings of this work, it
      appears that both recycled materials can be used to manufacture composites with
      high mechanical properties and low density.

PMID- 21172733
TI  - Serum C-reactive protein and lipid hydroperoxides in predicting short-term
      clinical outcome after spontaneous intracerebral hemorrhage.
AB  - There is no effective treatment for spontaneous intracerebral hemorrhage (sICH).
      We examined 46 patients with sICH within 48 hours after onset of symptoms, aiming
      to assess the predictive value of C-reactive protein (CRP) and lipid
      hydroperoxides (ROOH) on "first-week mortality" and "clinical outcome at
      discharge" by binary logistic regression. We found that serum CRP and hematoma
      volume were predictors of short-term mortality. Although serum ROOH level was
      positively correlated with mortality, it did not predict early lethal outcome.
      Serum ROOH concentration, however, was a predictor of poor clinical outcome in
      sICH survivors. After confirmation of the results obtained through observing a
      larger group of patients, an oxidative stress marker could be used as an
      additional criterion for patient stratification, especially when severe
      disability is expected and supplementary therapeutic approaches are urgent.

PMID- 21172734
TI  - Synthesis and evaluation of 6-[1-(2-[(18)F]fluoro-3-pyridyl)-5-methyl-1H-1,2,3
      triazol-4-yl]quinoline for positron emission tomography imaging of the
      metabotropic glutamate receptor type 1 in brain.
AB  - The purpose of this study was to synthesize 6-[1-(2-[(18)F]fluoro-3-pyridyl)-5
      methyl-1H-1,2,3-triazol-4-yl]quinoline ([(18)F]FPTQ, [(18)F]7a) and to evaluate
      its potential as a positron emission tomography ligand for imaging metabotropic
      glutamate receptor type 1 (mGluR1) in the rat brain. Compound [(18)F]7a was
      synthesized by [(18)F]fluorination of 6-[1-(2-bromo-3-pyridyl)-5-methyl-1H-1,2,3
      triazol-4-yl]quinoline (7b) with potassium [(18)F]fluoride. At the end of
      synthesis, 1280-1830MBq (n=8) of [(18)F]7a was obtained with >98% radiochemical
      purity and 118-237GBq/MUmol specific activity using 3300-4000MBq of [(18)F]F(-).
      In vitro autoradiography showed that [(18)F]7a had high specific binding with
      mGluR1 in the rat brain. Biodistribution study using a dissection method and
      small-animal PET showed that [(18)F]7a had high uptake in the rat brain. The
      uptake of radioactivity in the cerebellum was reduced by unlabeled 7a and mGluR1
      selective ligand JNJ-16259685 (2), indicating that [(18)F]7a had in vivo specific
      binding with mGluR1. Because of a low amount of radiolabeled metabolite present
      in the brain, [(18)F]7a may have a limiting potential for the in vivo imaging of
      mGluR1 by PET.

PMID- 21172736
TI  - The characterization of acoustic cavitation bubbles - an overview.
AB  - Acoustic cavitation, in simple terms, is the growth and collapse of preexisting
      microbubbles under the influence of an ultrasonic field in liquids. The
      cavitation bubbles can be characterized by the dynamics of oscillations and the
      maximum temperatures and pressures reached when they collapse. These aspects can
      be studied both experimentally and theoretically for a single bubble system.
      However, in a multibubble system, the formation of bubble streamers and clusters
      makes it difficult to characterize the cumulative properties of these bubbles. In
      this overview, some recently developed experimental procedures for the
      characterization of acoustic cavitation bubbles have been discussed.

PMID- 21172737
TI  - Electrosynthesis and characterization of conducting polypyrrole elaborated under
      high frequency ultrasound irradiation.
AB  - The effects of high frequency ultrasound (500kHz) on pyrrole
      electropolymerization in sodium perchlorate aqueous medium have been
      investigated. Cyclic voltametry studies showed that there is no influence on
      pyrrole oxidation potential. Scanning Electron Microscopy (SEM) imaging, and
      mechanical and optical profiling, revealed thinner, denser and more homogeneous
      surface structure for polypyrrole films elaborated under ultrasound irradiation.
      This is attributed to cavitation bubble asymmetric collapse close to the
      interface, which should induce changes in the nucleation-growth mechanism during
      the first polymerization stage. An increase of approximately 27% in doping level
      for sonicated films was revealed by X-ray Photoelectron Spectroscopy (XPS)
      analyses.

PMID- 21172735
TI  - Synthesis, antiprotozoal, antimicrobial, beta-hematin inhibition, cytotoxicity
      and methemoglobin (MetHb) formation activities of bis(8-aminoquinolines).
AB  - In continuing our search of potent antimalarials based on 8-aminoquinoline
      structural framework, three series of novel bis(8-aminoquinolines) using
      convenient one to four steps synthetic procedures were synthesized. The
      bisquinolines were evaluated for in vitro antimalarial (Plasmodiumfalciparum),
      antileishmanial (Leishmaniadonovani), antimicrobial (a panel of pathogenic
      bacteria and fungi), cytotoxicity, beta-hematin inhibitory and methemoglobin
      (MetHb) formation activities. Several compounds exhibited superior antimalarial
      activities compared to parent drug primaquine. Selected compounds (44, 61 and 79)
      when tested for in vivo blood-schizontocidal antimalarial activity
      (Plasmodiumberghei) displayed potent blood-schizontocial activities. The
      bisquinolines showed negligible MetHb formation (0.2-1.2%) underlining their
      potential in the treatment of glucose-6-phosphate dehydrogenase deficient
      patients. The bisquinoline analogues (36, 73 and 79) also exhibited promising in
      vitro antileishmanial activity, and antimicrobial activities (43, 44 and 76)
      against a panel of pathogenic bacteria and fungi. The results of this study
      provide evidence that bis(8-aminoquinolines), like their bis(4-aminoquinolines)
      and artemisinin dimers counterparts, are a promising class of antimalarial
      agents.

PMID- 21172738
TI  - Influence of ageing on the pharmacokinetics of levodopa in elderly patients with
      Parkinson's disease.
AB  - Levodopa (LD) is the most effective drug to treat the symptoms of Parkinson's
      disease (PD). It has been reported that the bioavailability of LD is higher in
      elderly patients than in young patients; however, it is not known how ageing
      changes the bioavailability of LD among elderly patients. In this study, we
      compared the pharmacokinetics of LD between two groups of elderly PD patients,
      early- (75 years or younger) and late-elderly (76 years or older). After oral
      administration of a tablet containing 100 mg LD per 10 mg carbidopa in 155 PD
      patients, we measured plasma LD concentrations. Peak drug concentration (C(max)),
      time to peak drug concentration (T(max)), halftime of drug (T1/2) and area under
      the curve (AUC) were determined. AUC and T1/2 were significantly higher and
      longer, respectively, in the late-elderly group than in the early-elderly group
      (p < 0.05 and <0.05, respectively). However, C(max) and T(max) were not
      statistically different between the groups. The present data indicate that LD
      absorption is consistent in PD patients, regardless of age. The difference in
      oral LD bioavailability between the groups may result from a difference in
      excretion ability. Physicians should consider LD pharmacokinetics when treating
      elderly PD patients.

PMID- 21172739
TI  - Decrease of spasticity with muscle vibration in patients with spinal cord injury.
AB  - OBJECTIVE: Spasticity is common after spinal cord injury (SCI). Exaggerated
      tendon jerks, clonus, and spasms are key features of spasticity that result from
      hyperexcitability of the stretch reflex circuit. Here we studied the effects of
      vibration on the rectus femoris muscle (RF) on clinical and electrophysiological
      measures of spasticity in the leg. METHODS: Nineteen SCI patients with spasticity
      and nine healthy subjects were studied at baseline and under stimulation
      (vibration at 50 Hz during 10 min on the thigh). Neurophysiological studies
      included evaluation of the soleus T wave and Hmax/Mmax ratio. Clinical
      measurements of spasticity were the score in the Modified Ashworth Scale (MAS),
      range of motion (ROM), and duration and frequency of clonus. RESULTS: Patients
      with incomplete SCI (iSCI) presented higher number of cycles and longer duration
      of clonus than patients with complete SCI (cSCI). The Hmax/Mmax ratio and T wave
      amplitude at baseline were significantly larger in iSCI patients than in cSCI or
      healthy subjects. During vibration, we found a significant reduction of MAS and
      duration of clonus, and an increase in ROM, in all patients as a group. The
      Hmax/Mmax ratio and the T wave amplitude decreased significantly in both,
      patients and controls. CONCLUSIONS: Prolonged vibration on proximal lower
      extremity muscles decreased limb spasticity in patients with spinal cord injury,
      regardless of whether the lesion is complete or incomplete. SIGNIFICANCE: Muscle
      vibration may be useful for physical therapy, by facilitating passive and active
      movements of the extremities in spastic SCI patients.

PMID- 21172740
TI  - Lactic acid bacterial fermentation on the production of functional antioxidant
      herbal Anoectochilus formosanus Hayata.
AB  - This study evaluated a novel use of the traditional Asian herb Anoectochilus
      formosanus. This plant is a traditional food item, generally used for the
      treatment of liver disorder, hepatitis, hypertension, diabetes, cardiovascular
      disorder, etc. In this study, the root, stem, and leaf of A. formosanus were used
      as substrates for lactic fermentation. The fermentation products were analyzed
      for their total antioxidant activity, reducing power, and scavenging effect on
      superoxide anion radicals and hydrogen peroxide. The pH of the fermentation
      medium reached its lowest value, 3.5, at the 35th hour of fermentation.
      Antioxidant activity of A. formosanus was found to be 61-78%. Lactobacillus
      longum-led fermentation exhibited the greatest reducing power with an average of
      0.3. The products of fermentations utilizing the three plant parts as substrates
      exhibited a similar scavenging activity (27-30%) on free radicals. This study may
      suggest a novel use of lactic-fermenting A. formosanus in the production of
      functional food.

PMID- 21172741
TI  - Maximising graduate status in pre-registration nursing programmes: utilising
      problem based learning.
AB  - This paper debates the use of problem based learning in accelerated pre
      registration nursing programmes that are specifically designed for candidates
      with 'graduate status'. We discuss the benefits of using problem based learning
      (PBL) within a graduate entry nursing (GEN) curriculum and its effectiveness in
      producing dynamic nurses who are both capable and value-centred practitioners.

PMID- 21172742
TI  - The iDUDE framework for grayscale image denoising.
AB  - We present an extension of the discrete universal denoiser DUDE, specialized for
      the denoising of grayscale images. The original DUDE is a low-complexity
      algorithm aimed at recovering discrete sequences corrupted by discrete memoryless
      noise of known statistical characteristics. It is universal, in the sense of
      asymptotically achieving, without access to any information on the statistics of
      the clean sequence, the same performance as the best denoiser that does have
      access to such information. The DUDE, however, is not effective on grayscale
      images of practical size. The difficulty lies in the fact that one of the DUDE's
      key components is the determination of conditional empirical probability
      distributions of image samples, given the sample values in their neighborhood.
      When the alphabet is relatively large (as is the case with grayscale images),
      even for a small-sized neighborhood, the required distributions would be
      estimated from a large collection of sparse statistics, resulting in poor
      estimates that would not enable effective denoising. The present work enhances
      the basic DUDE scheme by incorporating statistical modeling tools that have
      proven successful in addressing similar issues in lossless image compression.
      Instantiations of the enhanced framework, which is referred to as iDUDE, are
      described for examples of additive and nonadditive noise. The resulting denoisers
      significantly surpass the state of the art in the case of salt and pepper (S&P)
      and M -ary symmetric noise, and perform well for Gaussian noise.

PMID- 21172743
TI  - A uniform framework for estimating illumination chromaticity, correspondence, and
      specular reflection.
AB  - Based upon a new correspondence matching invariant called illumination
      chromaticity constancy, we present a new solution for illumination chromaticity
      estimation, correspondence searching, and specularity removal. Using as few as
      two images, the core of our method is the computation of a vote distribution for
      a number of illumination chromaticity hypotheses via correspondence matching. The
      hypothesis with the highest vote is accepted as correct. The estimated
      illumination chromaticity is then used together with the new matching invariant
      to match highlights, which inherently provides solutions for correspondence
      searching and specularity removal. Our method differs from the previous
      approaches: those treat these vision problems separately and generally require
      that specular highlights be detected in a preprocessing step. Also, our method
      uses more images than previous illumination chromaticity estimation methods,
      which increases its robustness because more inputs/constraints are used.
      Experimental results on both synthetic and real images demonstrate the
      effectiveness of the proposed method.

PMID- 21172744
TI  - No-reference blur assessment of digital pictures based on multifeature
      classifiers.
AB  - In this paper, we address the problem of no-reference quality assessment for
      digital pictures corrupted with blur. We start with the generation of a large
      real image database containing pictures taken by human users in a variety of
      situations, and the conduction of subjective tests to generate the ground truth
      associated to those images. Based upon this ground truth, we select a number of
      high quality pictures and artificially degrade them with different intensities of
      simulated blur (gaussian and linear motion), totalling 6000 simulated blur
      images. We extensively evaluate the performance of state-of-the-art strategies
      for no-reference blur quantification in different blurring scenarios, and propose
      a paradigm for blur evaluation in which an effective method is pursued by
      combining several metrics and low-level image features. We test this paradigm by
      designing a no-reference quality assessment algorithm for blurred images which
      combines different metrics in a classifier based upon a neural network structure.
      Experimental results show that this leads to an improved performance that better
      reflects the images' ground truth. Finally, based upon the real image database,
      we show that the proposed method also outperforms other algorithms and metrics in
      realistic blur scenarios.

PMID- 21172745
TI  - Fast H.264/AVC FRExt intra coding using belief propagation.
AB  - In the H.264/AVC FRExt coder, the coding performance of Intra coding
      significantly overcomes the previous still image coding standards, like JPEG2000,
      thanks to a massive use of spatial prediction. Unfortunately, the adoption of an
      extensive set of predictors induces a significant increase of the computational
      complexity required by the rate-distortion optimization routine. The paper
      presents a complexity reduction strategy that aims at reducing the computational
      load of the Intra coding with a small loss in the compression performance. The
      proposed algorithm relies on selecting a reduced set of prediction modes
      according to their probabilities, which are estimated adopting a belief
      propagation procedure. Experimental results show that the proposed method permits
      saving up to 60 % of the coding time required by an exhaustive rate-distortion
      optimization method with a negligible loss in performance. Moreover, it permits
      an accurate control of the computational complexity unlike other methods where
      the computational complexity depends upon the coded sequence.

PMID- 21172747
TI  - Automatic detection of obstructive sleep apnea using speech signals.
AB  - Obstructive sleep apnea (OSA) is a common disorder associated with anatomical
      abnormalities of the upper airways that affects 5% of the population. Acoustic
      parameters may be influenced by the vocal tract structure and soft tissue
      properties. We hypothesize that speech signal properties of OSA patients will be
      different than those of control subjects not having OSA. Using speech signal
      processing techniques, we explored acoustic speech features of 93 subjects who
      were recorded using a text-dependent speech protocol and a digital audio recorder
      immediately prior to polysomnography study. Following analysis of the study,
      subjects were divided into OSA (n=67) and non-OSA (n=26) groups. A Gaussian
      mixture model-based system was developed to model and classify between the
      groups; discriminative features such as vocal tract length and linear prediction
      coefficients were selected using feature selection technique. Specificity and
      sensitivity of 83% and 79% were achieved for the male OSA and 86% and 84% for the
      female OSA patients, respectively. We conclude that acoustic features from speech
      signals during wakefulness can detect OSA patients with good specificity and
      sensitivity. Such a system can be used as a basis for future development of a
      tool for OSA screening.

PMID- 21172748
TI  - Intervention in biological phenomena modeled by S-systems.
AB  - Recent years have witnessed extensive research activity in modeling biological
      phenomena as well as in developing intervention strategies for such phenomena. S
      systems, which offer a good compromise between accuracy and mathematical
      flexibility, are a promising framework for modeling the dynamical behavior of
      biological phenomena. In this paper, two different intervention strategies,
      namely direct and indirect, are proposed for the S-system model. In the indirect
      approach, the prespecified desired values for the target variables are used to
      compute the reference values for the control inputs, and two control algorithms,
      namely simple sampled-data control and model predictive control (MPC), are
      developed for transferring the control variables from their initial values to the
      computed reference ones. In the direct approach, a MPC algorithm is developed
      that directly guides the target variables to their desired values. The proposed
      intervention strategies are applied to the glycolytic-glycogenolytic pathway and
      the simulation results presented demonstrate the effectiveness of the proposed
      schemes.

PMID- 21172749
TI  - A minimally invasive antenna for microwave ablation therapies: design,
      performances, and experimental assessment.
AB  - A new coaxial antenna for microwave ablation therapies is proposed. The antenna
      design includes a miniaturized choke and an arrowhead cap to facilitate antenna
      insertion into the tissues. Antenna matching and the shape and dimension of the
      area of ablated tissue (thermal lesion) obtained in ex vivo conditions are
      evaluated both numerically and experimentally, finding an optimal agreement
      between numerical and experimental data. Results show that the antenna is well
      matched, and that it is able to produce a thermal lesion with an average length
      of 6.5 cm and an average diameter of 4.5 cm in ex vivo bovine liver when
      irradiates 60 W for 10 min. Finally, the dependence of antenna performances on
      possible changes in the antenna's structure is investigated, finding an optimal
      stability with respect to manufacturing tolerances and highlighting the
      fundamental role played by the antenna's choke.

PMID- 21172750
TI  - Adaptive sleep-wake discrimination for wearable devices.
AB  - Sleep/wake classification systems that rely on physiological signals suffer from
      intersubject differences that make accurate classification with a single, subject
      independent model difficult. To overcome the limitations of intersubject
      variability, we suggest a novel online adaptation technique that updates the
      sleep/wake classifier in real time. The objective of the present study was to
      evaluate the performance of a newly developed adaptive classification algorithm
      that was embedded on a wearable sleep/wake classification system called SleePic.
      The algorithm processed ECG and respiratory effort signals for the classification
      task and applied behavioral measurements (obtained from accelerometer and press
      button data) for the automatic adaptation task. When trained as a subject
      independent classifier algorithm, the SleePic device was only able to correctly
      classify 74.94 +/- 6.76% of the human-rated sleep/wake data. By using the
      suggested automatic adaptation method, the mean classification accuracy could be
      significantly improved to 92.98 +/- 3.19%. A subject-independent classifier based
      on activity data only showed a comparable accuracy of 90.44 +/- 3.57%. We
      demonstrated that subject-independent models used for online sleep-wake
      classification can successfully be adapted to previously unseen subjects without
      the intervention of human experts or off-line calibration.

PMID- 21172751
TI  - Component analysis approach to estimation of tissue intensity distributions of 3D
      images.
AB  - Many segmentation algorithms in medical imaging rely on accurate modeling and
      estimation of tissue intensity probability density functions. Gaussian mixture
      modeling, currently the most common approach, has several drawbacks, such as
      reliance on a Gaussian model and iterative local optimization used to estimate
      the model parameters. It also does not take advantage of substantially larger
      amount of data provided by 3D acquisitions, which are becoming standard in
      clinical environment. We propose a novel and completely non-parametric algorithm
      to estimate the tissue intensity probabilities in 3D images. Instead of relying
      on traditional framework of iterating between classification and estimation, we
      pose the problem as an instance of a blind source separation problem, where the
      unknown distributions are treated as sources and histograms of image subvolumes
      as mixtures. The new approach performed well on synthetic data and real magnetic
      resonance imaging (MRI) scans of the brain, robustly capturing intensity
      distributions of even small image structures and partial volume voxels.

PMID- 21172752
TI  - Paramer mismatch-based spectral gamut mapping.
AB  - A spectral agreement between the original scene and a printed reproduction is
      required to achieve an illuminant-invariant visual match. This is usually
      impossible since the spectral gamut of typical printing systems is only a small
      subset of all natural reflectances. Out-of gamut reflectances need to be mapped
      into the spectral gamut of the printer minimizing the perceived error between
      original and reproduction for more than one illuminant. In this paper, we propose
      an algorithmic framework for spectral gamut mapping to achieve a reproduction
      that is as visually correct as a colorimetric reproduction for one illuminant and
      is superior for a set of other illuminants. A sequence of hierarchical mappings
      in 3-D color spaces are performed utilizing the observer's color quantization to
      increase the spectral variability of subsequent transformations: For the most
      important illuminant a traditional colorimetric gamut mapping is performed. For
      any additional illuminants colors are mapped onto pixel-dependent paramer
      mismatch gamuts preserving the visual equivalence of previous transformations. We
      present a separation method for investigating the spectral gamut mapping
      framework and show that hue shifts and chroma gains cannot be always avoided for
      the second and subsequent illuminants and that the order of illuminants has a
      large impact on the final reproduction.

PMID- 21172753
TI  - Unequal protection of video data according to slice relevance.
AB  - In this paper, we devise a procedure that mimics the behavior of a progressive
      video stream starting from a non progressive one such as H.264/AVC encoded video.
      This allows one to unequally protect the video data in an efficient way,
      according to their importance and the network state. The reported results
      demonstrate the superior performance of the proposed approach in comparison to
      state-of-the-art methods for resilient transmission of H.264/AVC data. Moreover,
      the flexibility in terms of redundancy insertion and achieved quality levels,
      allows one to span different applications, possibly including P2P video
      streaming.

PMID- 21172754
TI  - Statistical-mechanics-inspired optimization of sensor field configuration for
      detection of mobile targets.
AB  - This paper presents a statistical-mechanics-inspired procedure for optimization
      of the sensor field configuration to detect mobile targets. The key idea is to
      capture the low-dimensional behavior of the sensor field configurations across
      the Pareto front in a multiobjective scenario for optimal sensor deployment,
      where the nondominated points are concentrated within a small region of the large
      dimensional decision space. The sensor distribution is constructed using location
      dependent energy-like functions and intensive temperature-like parameters in the
      sense of statistical mechanics. This low-dimensional representation is shown to
      permit rapid optimization of the sensor field distribution on a high-fidelity
      simulation test bed of distributed sensor networks.

PMID- 21172755
TI  - Mobile human network management and recommendation by probabilistic social
      mining.
AB  - Recently, inferring or sharing of mobile contexts has been actively investigated
      as cell phones have become more than a communication device. However, most of
      them focused on utilizing the contexts on social network services, while the
      means in mining or managing the human network itself were barely considered. In
      this paper, the SmartPhonebook, which mines users' social connections to manage
      their relationships by reasoning social and personal contexts, is presented. It
      works like an artificial assistant which recommends the candidate callees whom
      the users probably would like to contact in a certain situation. Moreover, it
      visualizes their social contexts like closeness and relationship with others in
      order to let the users know their social situations. The proposed method infers
      the social contexts based on the contact patterns, while it extracts the personal
      contexts such as the users' emotional states and behaviors from the mobile logs.
      Here, Bayesian networks are exploited to handle the uncertainties in the mobile
      environment. The proposed system has been implemented with the MS Windows Mobile
      2003 SE Platform on Samsung SPH-M4650 smartphone and has been tested on real
      world data. The experimental results showed that the system provides an efficient
      and informative way for mobile social networking.

PMID- 21172756
TI  - Building high-performing human-like tactical agents through observation and
      experience.
AB  - This paper describes a two-phase approach for automating the agent-building
      process when the agent is to perform tactical tasks. The research is inspired by
      how humans learn-first by observation of a teacher's performance and then by
      practicing the performance themselves. The objectives of this approach are to
      produce a high-performing agent that 1) approaches or exceeds the proficiency of
      a human and 2) does so in a human-like manner. We accomplish these objectives by
      combining observational learning with experiential learning. These processes are
      executed sequentially, with the former creating a competent but somewhat limited
      human-like model from scratch, and the latter improving its performance without
      significantly eroding its human-like qualities. The process is described in
      detail, and test results confirming our hypothesis are described.

PMID- 21172757
TI  - Guest editorial: introduction to the special issue on citizen centered e-Health
      systems in a global healthcare environment: selected papers from ITAB 2009.

PMID- 21172758
TI  - Traffic-related air pollution and cognitive function in a cohort of older men.
AB  - BACKGROUND: Traffic-related particles induce oxidative stress and may exert
      adverse effects on central nervous system function, which could manifest as
      cognitive impairment. OBJECTIVE: We assessed the association between black carbon
      (BC), a marker of traffic-related air pollution, and cognition in older men.
      METHODS: A total of 680 men (mean +/- SD, 71 +/- 7 years of age) from the U.S.
      Department of Veterans Affairs Normative Aging Study completed a battery of seven
      cognitive tests at least once between 1996 and 2007. We assessed long-term
      exposure to traffic-related air pollution using a validated spatiotemporal land
      use regression model for BC. RESULTS: The association between BC and cognition
      was nonlinear, and we log-transformed BC estimates for all analyses [ln(BC)]. In
      a multivariable-adjusted model, for each doubling in BC on the natural scale, the
      odds of having a Mini-Mental State Examination (MMSE) score <= 25 was 1.3 times
      higher [95% confidence interval (CI), 1.1 to 1.6]. In a multivariable-adjusted
      model for global cognitive function, which combined scores from the remaining six
      tests, a doubling of BC was associated with a 0.054 SD lower test score (95% CI, 
      0.103 to -0.006), an effect size similar to that observed with a difference in
      age of 1.9 years in our data. We found no evidence of heterogeneity by cognitive
      test. In sensitivity analyses adjusting for past lead exposure, the association
      with MMSE scores was similar (odds ratio = 1.3; 95% CI, 1.1 to 1.7), but the
      association with global cognition was somewhat attenuated (-0.038 per doubling in
      BC; 95% CI, -0.089 to 0.012). CONCLUSIONS: Ambient traffic-related air pollution
      was associated with decreased cognitive function in older men.

PMID- 21172759
TI  - Distributed lag analyses of daily hospital admissions and source-apportioned fine
      particle air pollution.
AB  - BACKGROUND: Past time-series studies of the health effects of fine particulate
      matter [aerodynamic diameter <= 2.5 um (PM2.5)] have used chemically nonspecific
      PM2.5 mass. However, PM2.5 is known to vary in chemical composition with source,
      and health impacts may vary accordingly. OBJECTIVE: We tested the association
      between source-specific daily PM2.5 mass and hospital admissions in a time-series
      investigation that considered both single-lag and distributed-lag models.
      METHODS: Daily PM2.5 speciation measurements collected in midtown Manhattan were
      analyzed via positive matrix factorization source apportionment. Daily and
      distributed-lag generalized linear models of Medicare respiratory and
      cardiovascular hospital admissions during 2001-2002 considered PM2.5 mass and
      PM2.5 from five sources: transported sulfate, residual oil, traffic, steel metal
      works, and soil. RESULTS: Source-related PM2.5 (specifically steel and traffic)
      was significantly associated with hospital admissions but not with total PM2.5
      mass. Steel metal works-related PM2.5 was associated with respiratory admissions
      for multiple-lag days, especially during the cleanup efforts at the World Trade
      Center. Traffic-related PM2.5 was consistently associated with same-day
      cardiovascular admissions across disease-specific subcategories. PM2.5
      constituents associated with each source (e.g., elemental carbon with traffic)
      were likewise associated with admissions in a consistent manner. Mean effects of
      distributed-lag models were significantly greater than were maximum single-day
      effect models for both steel- and traffic-related PM2.5. CONCLUSIONS: Past
      analyses that have considered only PM2.5 mass or only maximum single-day lag
      effects have likely underestimated PM2.5 health effects by not considering source
      specific and distributed-lag effects. Differing lag structures and disease
      specificity observed for steel-related versus traffic-related PM2.5 raise the
      possibility of distinct mechanistic pathways of health effects for particles of
      differing chemical composition.

PMID- 21172760
TI  - Introduction to medication regimen review-part 2.
AB  - Drug therapy is one of a variety of tools used by clinicians to manage symptoms
      and diseases in patients. To understand the medication regimen review process, it
      is important to understand the big picture of patient care and how medications
      fit into this overall scheme. The framework for patient management is known as
      "the care process."

PMID- 21172761
TI  - Off-label use of medications: innovative prescribing or risky business?
AB  - Off-label use of medication is common and can lead to innovations in the use of
      medicine to treat patients in unconventional ways. However, issues of increased
      health care costs, decreased reimbursement, and lack of clinical data to support
      off-label use, are concerns of practitioners and patients alike. By using their
      knowledge of medications and carefully examining the existing research,
      pharmacists can aid prescribers in appropriate off-label medication use.

PMID- 21172762
TI  - Oral hydromorphone extended-release.
AB  - OBJECTIVE: To review the chemistry, pharmacodynamics, pharmacokinetics, efficacy,
      tolerability, dosing, and role of the Osmotic-controlled Release Oral delivery
      System (OROS) hydromorphone extended-release (ER) tablets. DATA SOURCE: A
      MEDLINE/PUBMED search (1986-August 2010) was conducted to identify studies in the
      English language, with additional references being obtained from their
      bibliographies. STUDY SELECTION: All studies of hydromorphone ER were reviewed.
      DATA SYNTHESIS: This is the second long-acting hydromorphone formulation to
      receive approval by the Food and Drug Administration (a twice-daily formulation
      was approved in September 2004, but was subsequently withdrawn in July 2005).
      Hydromorphone is a semi-synthetic mu-opioid receptor agonist structurally similar
      to morphine, hydrocodone, and oxymorphone. OROS ER technology allows once-daily
      dosing. Clinical trials have focused on the convertibility of (an) other
      opioid(s) to hydromorphone ER in chronic malignant and nonmalignant pain. This
      product displays the expected opioid side effects, being comparable to oxycodone
      controlled-release. Coadministration with ethanol does not produce the degree of
      "dose-dumping" seen with the former hydromorphone twice-daily product or
      oxymorphone ER. Hydromorphone ER is indicated for the management of moderate-to
      severe pain in opioidtolerant patients requiring continuous, around-the-clock
      opioid analgesia for an extended period of time. Dosage adjustment is recommended
      in patients with moderate hepatic impairment (Child-Pugh class B) and moderate
      renal impairment (creatinine clearance of 30-60 mL/min). CONCLUSION:
      Hydromorphone ER is the newest oral opioid to enter a crowded marketplace now
      totaling 15 different Schedule 2 opioids (including tapentadol), and tramadol,
      available in oral, parenteral, rectal, transdermal, transmucosal, and intranasal
      formulations. It does not appear to have any unique assets or liabilities and
      should be considered as one of many oral opioids available for the management of
      persistent pain of moderate-to-severe intensity.

PMID- 21172763
TI  - Medication reconciliation: an important piece of the medication puzzle.
AB  - Medication errors continue to cause significant morbidity and mortality. This, in
      turn, costs the health care system millions of dollars each year in preventable
      costs. Medication reconciliation, an important piece of medication therapy
      management (MTM), is vital to reducing medication errors. By verifying,
      clarifying, and reconciling medications at each point of care, pharmacists can
      play a vital role in improving health care and lowering costs. This case study
      describes an MTM session with a 66-year-old Caucasian female who is referred by
      the nurse practitioner in the clinic for pharmacist services. The patient has a
      history of portal hypertension, alcoholic liver damage, and chronic obstructive
      pulmonary disease. After obtaining a detailed history, the pharmacist identified
      significant medication-related problems including polypharmacy, nonadherence,
      drug-alcohol interactions, and inappropriate use of medication. After discussions
      with the patient and her nurse practitioner, a medication plan was created for
      the patient to follow.

PMID- 21172764
TI  - Clostridium difficile-associated disease: impact of the updated SHEA/IDSA
      guidelines.
AB  - Clostridium difficile-associated disease (CDAD) is an increasingly difficult
      condition to treat because of the emergence of antibiotic resistance and highly
      pathogenic strains of bacteria. These newly identified strains affect patients in
      every facet of health care, from individuals in the community to those in
      intensive care units and all points in between. Appropriate management regarding
      diagnosis, infection control, pharmacotherapy, and prevention is the key to good
      outcomes in all patient populations. Geriatric patients are particularly at risk
      of acquiring CDAD as a result of their gradually declining immune systems and
      increased exposure to health care facilities. Therefore, they merit a higher
      level of attention when CDAD is suspected. In an effort to identify the best
      practices, the Society for Healthcare Epidemiology of America in conjunction with
      the Infectious Diseases Society of America developed guidelines regarding the
      diagnosis and management of Clostridium-associated disease. By utilizing these
      guidelines to educate other health care practitioners and by considering the
      recommendations in their own practice, pharmacists can have a positive impact on
      every facet of CDAD prevention and management.

PMID- 21172767
TI  - The second version of the Copenhagen Psychosocial Questionnaire.
AB  - AIMS: The aim of the present paper is to present the development of the second
      version of the Copenhagen Psychosocial Questionnaire (COPSOQ II). METHODS: The
      development of COPSOQ II took place in five main steps: (1) We considered
      practical experience from the use of COPSOQ I, in particular feedback from
      workplace studies where the questionnaire had been used; (2) All scales
      concerning workplace factors in COPSOQ I were analyzed for differential item
      functioning (DIF) with regard to gender, age and occupational status; (3) A test
      version of COPSOQ II including new scales and items was developed and tested in a
      representative sample of working Danes between 20 and 59 years of age. In all,
      3,517 Danish employees participated in the study. The overall response rate was
      60.4%; (4) Based on psychometric analyses, the final questionnaire was developed;
      and (5) Criteria-related validity of the new scales was tested. RESULTS: The
      development of COPSOQ II resulted in a questionnaire with 41 scales and 127
      items. New scales on values at the workplace were introduced including scales on
      Trust, Justice and Social inclusiveness. Scales on Variation, Work pace,
      Recognition, Work-family conflicts and items on offensive behaviour were also
      added. New scales regarding health symptoms included: Burnout, Stress, Sleeping
      troubles and Depressive symptoms. In general, the new scales showed good criteria
      validity. All in all, 57% of the items of COPSOQ I were retained in COPSOQ II.
      CONCLUSIONS: The COPSOQ I concept has been further developed and new validated
      scales have been included.

PMID- 21172765
TI  - Feasibility of an eHealth service to support collaborative depression care:
      results of a pilot study.
AB  - BACKGROUND: Treatments and organizational changes supported by eHealth are
      beginning to play an important role in improving disease treatment outcome and
      providing cost-efficient care management. "Improvehealth.eu" is a novel eHealth
      service to support the treatment of patients with depressive disorder. It offers
      active patient engagement and collaborative care management by combining Web- and
      mobile-based information and communication technology systems and access to care
      managers. OBJECTIVES: Our objective was to assess the feasibility of a novel
      eHealth service. METHODS: The intervention--the "Improvehealth.eu" service--was
      explored in the course of a pilot study comparing two groups of patients
      receiving treatment as usual and treatment as usual with eHealth intervention. We
      compared patients' medication adherence and outcome measures between both groups
      and additionally explored usage and overall perceptions of the intervention in
      intervention group. RESULTS: The intervention was successfully implemented in a
      pilot with 46 patients, of whom 40 were female. Of the 46 patients, 25 received
      treatment as usual, and 21 received the intervention in addition to treatment as
      usual. A total of 55% (12/25) of patients in the former group and 45% (10/21) in
      the latter group finished the 6-month pilot. Available case analysis indicated an
      improvement of adherence in the intervention group (odds ratio [OR] = 10.0, P =
      .03). Intention-to-treat analysis indicated an improvement of outcome in the
      intervention group (ORs ranging from 0.35 to 18; P values ranging from .003 to
      .20), but confidence intervals were large due to small sample sizes. Average
      duration of use of the intervention was 107 days. The intervention was well
      received by 81% (17/21) of patients who reported feeling actively engaged, in
      control of their disease, and that they had access to a high level of
      information. In all, 33% (7/21) of the patients also described drawbacks of the
      intervention, mostly related to usability issues. CONCLUSIONS: The results of
      this pilot study indicate that the intervention was well accepted and helped the
      patients in the course of treatment. The results also suggest the potential of
      the intervention to improve both medication adherence and outcome measures of
      treatment, including reduction of depression severity and patients becoming
      "healthy."

PMID- 21172768
TI  - Reliability of the Copenhagen Psychosocial Questionnaire.
AB  - AIMS: Reliabilities of the work environment questionnaire Copenhagen Psychosocial
      Questionnaire (COPSOQ) have previously been estimated by Cronbach's alpha, but
      since the internal consistency assumption may not apply to all COPSOQ scales,
      Cronbach's alpha may underestimate true reliability. This study aims to evaluate
      reliability in a test-retest design. METHODS: We analyzed postal questionnaire
      data from 349 persons (of whom 283 were employees) who completed two forms with a
      median interval of 22 (range 6-65) days between baseline and follow-up. Test
      retest reliabilities were estimated by the intraclass correlation (ICC). For
      scales where the internal consistency assumption was theoretically plausible,
      reliabilities were also estimated by Cronbach's alpha and by Green's test-retest
      alpha. RESULTS: With one exception, the ICC estimated reliabilities of the COPSOQ
      scales were adequate or good (range 0.70-0.89). A scale concerning mutual trust
      between employees had a low reliability of 0.64. Among the scales where the
      internal consistency assumption was plausible, Cronbach's alpha was adequate or
      good (0.75-0.85) for seven out of eight scales. Green's retest alpha was adequate
      or good for six out of eight scales (0.72-0.81). CONCLUSIONS: Standard criteria
      for acceptable intraclass correlation reliability were achieved for all COPSOQ
      scales but one. The test-retest design and intraclass correlation appears to be
      more appropriate than Cronbach's alpha for assessing the reliability of
      psychosocial work environment scales.

PMID- 21172769
TI  - Determining minimally important score differences in scales of the Copenhagen
      Psychosocial Questionnaire.
AB  - AIM: To determine minimally important differences (MIDs) for scales in the first
      version of the Copenhagen Psychosocial Questionnaire (COPSOQ). METHODS: Data were
      taken from two separate studies: a national population survey (N = 1062), and an
      intervention study at 14 workplaces (N = 1505). On the basis of the population
      survey, the MID for each COPSOQ scale was calculated as one-half of a standard
      deviation (0.5 SD). For the core COPSOQ scales on ''Quantitative demands'',
      ''Influence at work'', ''Predictability'', ''Social support (from colleagues and
      supervisors, respectively)'', and ''Job satisfaction'', the MIDs were evaluated
      in the intervention study, where score differences for the scales were linked to
      the respondents' global self-evaluation of the impact of the interventions. The
      scales were scored from 0 to 100 in both studies. RESULTS: The MIDs calculated as
      0.5 SD were, on average, 9.2 (range 6.8-14.9) for the long version scales, and
      10.8 (range 7.6-14.9) for the medium-length version scales. The analysis of the
      self-evaluated changes on the scale scores for the core COPSOQ scales showed that
      the anchor-based estimates of MID were generally lower than 0.5 SD. CONCLUSIONS:
      We recommend the following MID values for the COPSOQ scales: ''Quantitative
      demands'', 0.3 SD; ''Influence'', 0.2 SD; ''Predictability'', 0.3 SD; ''Social
      support from colleagues'', 0.3 SD; ''Social support from supervisor'', 0.7 SD;
      and ''Job satisfaction'', 0.4 SD. For all other COPSOQ scales, where we do not
      have anchor-based results, we recommend the conventional MID value of 0.5 SD.

PMID- 21172770
TI  - Do psychosocial work environment factors measured with scales from the Copenhagen
      Psychosocial Questionnaire predict register-based sickness absence of 3 weeks or
      more in Denmark?
AB  - AIMS: To analyse the predictive validity of 18 psychosocial work environment
      scales from the Copenhagen Psychosocial Questionnaire version II (COPSOQ II) with
      regard to risk of sickness absence. METHODS: The study population consisted of
      3188 wage earners (52% women) from a representative sample of Danish residents.
      Participants received the long version of the COPSOQ II in autumn and winter 2004
      2005, including 18 psychosocial work environment scales from the domains
      ''Demands at work'', ''Work organization and job contents'', and ''Interpersonal
      relations and leadership''. The study endpoint was register-based sickness
      absence of 3 weeks or more in the 1-year period following completion of the
      COPSOQ II. Associations between COPSOQ scales at baseline and sickness absence at
      follow-up were analysed with Cox proportional hazards models, adjusted for age,
      gender, prevalence of a health problem at baseline, and occupational grade.
      RESULTS: Sickness absence during follow-up was predicted by a one standard
      deviation increase on the scales of cognitive demands (hazard ratio (HR) 1.17,
      95% confidence interval (CI) 1.00-1.37), emotional demands (HR 1.28, 95% CI 1.10
      1.50), and role conflicts (HR 1.32, 95% CI 1.15-1.52). After applying adjustment
      for multiple testing, the effect of emotional demands and of role conflict
      remained statistically significant, but not the effect of cognitive demands.
      CONCLUSIONS: Selected psychosocial work environment factors from the COPSOQ
      predict register-based sickness absence in the Danish workforce.

PMID- 21172771
TI  - Positive work-related states and long-term sickness absence: a study of register
      based outcomes.
AB  - AIMS: To investigate the association between positive work-related states and
      long-term sickness absence (LTSA). The positive states that were investigated
      were commitment to the work-place (CW) and experience of meaning of work (MW).
      METHODS: This association was investigated using Poisson regression analysis.
      Data consisted of a merge between Danish register data on sickness absence
      compensation and survey data collected among 9,560 employees in the Danish
      eldercare sector. RESULTS: CW and MW were significantly associated with LTSA.
      Employees experiencing low MW had a significantly increased risk of LTSA for more
      than two and eight weeks, when adjusted for psychosocial work characteristics,
      work-time arrangements and physical workload. Compared to employees with low and
      high CW, employees with medium CW had a significantly decreased risk of LTSA for
      more than eight weeks, when adjusted for psychosocial work characteristics, work
      time arrangements and physical workload. Furthermore, employees with low CW had
      an increased risk of LTSA for more than two weeks, but this association became
      borderline insignificant when adjusted for psychosocial work characteristics,
      work-time arrangements and physical workload. The analyses also revealed an
      interaction effect between CW and MW in predicting LTSA for more than eight
      weeks. CONCLUSIONS: CW and MW are associated with LTSA. Against our expectations,
      however, we found that high levels of CW and MW were not protective against LTSA.
      Instead, low levels of MW proved decisive in predicting LTSA, and medium levels
      of CW had a protective effect on LTSA for more than eight weeks.

PMID- 21172772
TI  - Do dimensions from the Copenhagen Psychosocial Questionnaire predict vitality and
      mental health over and above the job strain and effort-reward imbalance models?
AB  - AIMS: The Copenhagen Psychosocial Questionnaire (COPSOQ) comprises dimensions
      (emotional demands, demands of hiding emotions, meaning of work, quality of
      leadership, and predictability) that are not in the job strain or the effort
      reward imbalance (ERI) models. The study aim was to investigate whether these
      dimensions explain changes in vitality and mental health over and above the job
      strain and ERI models. METHODS: A cohort of 3552 employees in 2000 were followed
      up in 2005 (cohort participation of 51%). Regression analyses were carried out
      with mental health and vitality as dependent variables. A significance level of
      0.01 was applied when comparing regression models. RESULTS: Regarding mental
      health, both the full COPSOQ-ERI model (p = 0.005) and the full job strain-COPSOQ
      model (p = 0.01) were significantly better than the ERI and the job strain
      models. Regarding vitality, none of the full COPSOQ models (i.e. with new COPSOQ
      dimensions together with job strain or ERI respectively) was significantly better
      than the ERI (p = 0.03) or the job strain (p = 0.04) models. Emotional demands
      and low meaning of work predicted poor mental health and low vitality.
      CONCLUSIONS: In relation to mental health, new psychosocial risk factors have the
      potential to add to the predictive power of the job strain and ERI models. The
      current practice of including only items from the ERI and job strain models in
      public health studies should be reconsidered. Theories regarding the status of,
      for example, emotional demands and meaning of work should be developed and
      tested.

PMID- 21172773
TI  - Psychosocial work environment and intention to leave the nursing profession:
      results from the longitudinal Chinese NEXT study.
AB  - AIMS: A shortage of nurses happens not only in developed countries, but also in
      developing countries, such as in China, but the nurse turnover here makes the
      situation worse. Why do Chinese nurses want to leave the nursing profession? Our
      hypothesis is that unfavourable psychosocial work environment could predict
      nurses' intention to leave (ITL). METHODS: Collaborating with the EU NEXT study
      (Nurses' Early eXit sTudy), the longitudinal study was conducted in China, and
      the psychosocial work environment was measured with the Copenhagen Psychosocial
      Questionnaire (COPSOQ). A total of 3,088 registered female nurses working in
      hospitals were eligible for the baseline analyses by multivariate logistic
      regression, and 1,521 for the one-year follow-up analyses by multivariate Poisson
      regression. RESULTS: A wide range of psychosocial factors at work--in particular,
      increased emotional demands, decreased meaning of work, decreased commitment to
      the workplace, and decreased job satisfaction--were associated with ITL in both
      baseline analyses and prospective analyses after adjusting for numerous
      confounders. CONCLUSIONS: The findings suggest that unfavourable psychosocial
      work environment predicts ITL in Chinese nurses. Improvements in the psychosocial
      work environment may be helpful in retention of the nursing workforce.

PMID- 21172774
TI  - The effect of the work environment and performance-based self-esteem on cognitive
      stress symptoms among Danish knowledge workers.
AB  - AIMS: Interpersonal relations at work as well as individual factors seem to play
      prominent roles in the modern labour market, and arguably also for the change in
      stress symptoms. The aim was to examine whether exposures in the psychosocial
      work environment predicted symptoms of cognitive stress in a sample of Danish
      knowledge workers (i.e. employees working with sign, communication or exchange of
      knowledge) and whether performance-based self-esteem had a main effect, over and
      above the work environmental factors. METHODS: 349 knowledge workers, selected
      from a national, representative cohort study, were followed up with two data
      collections, 12 months apart. We used data on psychosocial work environment
      factors and cognitive stress symptoms measured with the Copenhagen Psychosocial
      Questionnaire (COPSOQ), and a measurement of performance-based self-esteem.
      Effects on cognitive stress symptoms were analyzed with a GLM procedure with and
      without adjustment for baseline level. RESULTS: Measures at baseline of
      quantitative demands, role conflicts, lack of role clarity, recognition,
      predictability, influence and social support from management were positively
      associated with cognitive stress symptoms 12 months later. After adjustment for
      baseline level of cognitive stress symptoms, follow-up level was only predicted
      by lack of predictability. Performance-based self-esteem was prospectively
      associated with cognitive stress symptoms and had an independent effect above the
      psychosocial work environment factors on the level of and changes in cognitive
      stress symptoms. CONCLUSIONS: The results suggest that both work environmental
      and individual characteristics should be taken into account in order to capture
      sources of stress in modern working life.

PMID- 21172775
TI  - Evaluating construct validity of the second version of the Copenhagen
      Psychosocial Questionnaire through analysis of differential item functioning and
      differential item effect.
AB  - AIMS: To evaluate the construct validity of the Copenhagen Psychosocial
      Questionnaire II (COPSOQ II) by means of tests for differential item functioning
      (DIF) and differential item effect (DIE). METHODS: We used a Danish general
      population postal survey (n = 4,732 with 3,517 wage earners) with a one-year
      register based follow up for long-term sickness absence. DIF was evaluated
      against age, gender, education, social class, public/private sector employment,
      and job type using ordinal logistic regression. DIE was evaluated against job
      satisfaction and self-rated health (using ordinal logistic regression), against
      depressive symptoms, burnout, and stress (using multiple linear regression), and
      against long-term sick leave (using a proportional hazards model). We used a
      cross-validation approach to counter the risk of significant results due to
      multiple testing. RESULTS: Out of 1,052 tests, we found 599 significant instances
      of DIF/DIE, 69 of which showed both practical and statistical significance across
      two independent samples. Most DIF occurred for job type (in 20 cases), while we
      found little DIF for age, gender, education, social class and sector. DIE seemed
      to pertain to particular items, which showed DIE in the same direction for
      several outcome variables. DISCUSSION: The results allowed a preliminary
      identification of items that have a positive impact on construct validity and
      items that have negative impact on construct validity. These results can be used
      to develop better shortform measures and to improve the conceptual framework,
      items and scales of the COPSOQ II. CONCLUSIONS: We conclude that tests of DIF and
      DIE are useful for evaluating construct validity.

PMID- 21172776
TI  - When workplace interventions lead to negative effects: learning from failures.
AB  - AIMS: To investigate if workplace interventions resulted in changes in the
      psychosocial work environment. Process evaluation was conducted to study the
      implementation process and to use this knowledge to understand the results.
      METHODS: Seven intervention units (n = 128) and seven non-randomized reference
      units (n = 103) of a large hospital in Denmark participated in an intervention
      project with the goal of improving the psychosocial working conditions. The
      intervention consisted of discussion days for all staff, employee working groups,
      leader coaching, and activities to improve communication and cooperation.
      Measures of the psychosocial work environment were conducted before the start of
      the intervention and again after 16 months using 13 scales from the Copenhagen
      Psychosocial Questionnaire, version I (COPSOQ I). RESULTS: In the intervention
      units there was a statistically significant worsening in six out of 13 work
      environment scales. The decrease was most pronounced for three scales that
      measure aspects of interpersonal relations and leadership. In addition, all three
      scales that measure aspects of work organization and job content decreased. In
      comparison, the reference group showed statistically significant changes in only
      two scales. Process evaluation revealed that a large part of the implementation
      failed and that different implicit theories were at play. CONCLUSIONS: Without
      the insights gained from process data the negative effects of this intervention
      could not be understood. Sometimes--as it seems happened in this study--more harm
      can be done by disappointing expectations than by not conducting an intervention.

PMID- 21172777
TI  - The Copenhagen Psychosocial Questionnaire in Germany: from the validation of the
      instrument to the formation of a job-specific database of psychosocial factors at
      work.
AB  - The German version of the Copenhagen Psychosocial Questionnaire (COPSOQ) was
      established and tested in a sample of 2561 employees in order to: (a) assess the
      questionnaires' psychometric properties; and (b) develop an appropriate
      instrument to use in the assessment of psychosocial risk factors. A shortened
      version of the instrument was developed, reducing the number of items from 141 to
      87. With this, a database has been established since 2005. In a cooperation model
      between science (Freiburg Research Centre of Occupational and Social Medicine)
      and companies or organizations, new COPSOQ data are added to the dynamically
      growing database with profession-specific profiles of psychosocial factors at
      work. In return, companies can compare their results with job-related data in the
      database, facilitating the interpretation of their results and the implementation
      of improvement measures. The COPSOQ database has reached > 25,000 respondents.
      Ongoing projects will expand the German COPSOQ database and include
      representative samples. Furthermore, a job exposure matrix for psychosocial
      factors at work will be constructed in 2009. Finally, in several projects, a
      first assessment has been followed by efforts to improve the problematic areas of
      psychosocial working conditions.

PMID- 21172778
TI  - Psychosocial risk exposures and labour management practices. An exploratory
      approach.
AB  - AIM: The purpose was to explore the relationship between psychosocial risk
      exposures and labour management practices (LMP), as indicators of work
      organization and pertinent features for primary preventive intervention. METHODS:
      Cross-sectional study of a representative sample of salaried working population
      in Spain (n = 7,612). Information was obtained in 2004-2005 using a standardized
      questionnaire administered through personal interviews at the household.
      Questions on working conditions were used to establish LMP indicators and the
      psychosocial exposures data were obtained on the basis of the Copenhagen
      Psychosocial Questionnaire (COPSOQ) I (ISTAS21). A multivariate description was
      performed through multiple correspondence analysis, and associations between LMPs
      and psychosocial exposures were assessed by ordinal logistic analysis adjusting
      for age and sex. RESULTS: Correspondence analysis showed a good-bad coherent
      pattern regarding both psychosocial dimension and LMPs, though several LMPs
      categories were placed in the centre. Among the 14 possible associations of each
      psychosocial scale with LMP variables, several scales showed significant
      associations with more than eight LMP variables. Most relevant results referred
      to the LMP variable ''Consultative and delegative participation in methods''.
      CONCLUSIONS: In line with previous research, psychosocial exposures were
      associated with LMP. LMP may constitute a step on a pathway from work
      organization to health. Our exploratory work suggested that good psychosocial
      exposures were related to participatory working methods, being hired with a
      permanent labour contract, not being made to feel easily replaceable, having
      superiors with non-authoritarian and non-aggressive manners, not being threatened
      with dismissal, upward functional mobility, being paid according to the number of
      working hours and occupation, working between 31 and 40 hours per week and in
      regular morning shifts. Hence, the more these features became part of LMP in the
      workplace, the better the psychosocial work environment would be.

PMID- 21172779
TI  - Psychosocial work environment and its association with socioeconomic status. A
      comparison of Spain and Denmark.
AB  - AIMS: The purpose of this study was to describe psychosocial work environment
      inequalities among wage earners in Spain and Denmark. METHODS: Data came from the
      Spanish COPSOQ (ISTAS 21) and the Danish COPSOQ II surveys both performed in 2004
      05 and based on national representative samples of employees with a 60% response
      rate. Study population was 3,359 Danish and 6,685 Spanish women and men. Only
      identical items from both surveys were included to construct 18 psychosocial
      scales. Socioeconomic status was categorized according to the European
      Socioeconomic Classification System. Analysis included ordinal logistic
      regression and multiple correspondence analysis after categorizing all scales.
      RESULTS: A relationship between socioeconomic status and psychosocial work
      environment in both Denmark and Spain was observed, with wider social
      inequalities in Spain for many scales, describing a strong interaction effect
      between socioeconomic status and country. CONCLUSIONS: Socioeconomic status is
      related to psychosocial work environment and some adverse psychosocial conditions
      tend to cluster in lower socioeconomic status groups in both Spain and Denmark.
      This effect could be modified by a country's characteristics, such as economic
      and labour market structures, normative regulations and industrial relations
      including work organization. Hence, preventive strategies to reduce social
      inequalities in working conditions should consider the combination of actions at
      the macro and micro levels.

PMID- 21172780
TI  - A questionnaire is more than a questionnaire.

PMID- 21172781
TI  - Isolation of fluoroquinolone-resistant O25b:H4-ST131 Escherichia coli with CTX-M
      14 extended-spectrum beta-lactamase from UK river water.
AB  - OBJECTIVES: We analysed water sampled from the River Thames in London for
      Escherichia coli resistant to oxyimino-cephalosporins and/or fluoroquinolones,
      particularly seeking isolates with CTX-M extended-spectrum beta-lactamases
      (ESBLs) and members of the clinically important O25b:H4-ST131 lineage. METHODS:
      River water was collected from three urban sites on the River Thames by the City
      of London Port Health Authority on two occasions 1 week apart. Coliforms and E.
      coli were identified by the Quanti-TrayTM method. Disc susceptibility tests were
      performed and MICs were determined for E. coli isolates resistant to either
      ciprofloxacin or cefpodoxime and genetic relatedness was determined by PFGE and
      real-time PCR. PCR was used for phylogenetic and plasmid typing, to detect
      antibiotic resistance genes and to detect ISEcp1 upstream of bla(CTX-M) genes.
      bla(CTX-M) alleles were identified by sequencing. RESULTS: The mean E. coli
      count, as the most probable number, from the first river samples, taken on a
      falling tide on 23 March 2010, was 4.7 * 10(4)/100 mL and 30 ciprofloxacin
      resistant colonies were isolated. Twenty of the 30 colonies belonged to clone
      ST131; 10 of these had bla(CTX-M-14) whereas the remaining 10 lacked ESBLs. The
      ST131 isolates represented two different PFGE types. No ciprofloxacin- or
      cefpodoxime-resistant E. coli were isolated from the second river sample taken at
      low tide. CTX-M-15, the most common ESBL in clinical E. coli, was not detected in
      the river samples. CONCLUSIONS: Water from the River Thames in West London is
      contaminated, perhaps transiently, with antibiotic-resistant E. coli belonging to
      the clinically important O25b:H4-ST131 lineage.

PMID- 21172782
TI  - Correlation of in vitro activity and in vivo efficacy of itraconazole intravenous
      and oral solubilized formulations by testing Candida strains with various
      itraconazole susceptibilities in a murine invasive infection.
AB  - OBJECTIVES: To examine whether in vitro antifungal susceptibility test results
      correlate with in vivo efficacy of two cyclodextrin-solubilized itraconazole
      formulations (intravenous and oral) against Candida in a murine model of invasive
      infection. METHODS: A selected set of 12 Candida spp. strains with various
      itraconazole susceptibilities were tested. We studied the efficacy of intravenous
      and oral itraconazole administered once daily at dosages of 0.63, 2.5, 10 and 40
      mg/kg body weight in mice lethally infected with each tested strain. Survival of
      mice in each treated group was monitored daily until the death of all control
      mice and compared between groups. RESULTS: Survival of mice infected with 9 of 12
      Candida strains with itraconazole MICs of <=0.016-2.0 mg/L was significantly
      prolonged by treatment with intravenous itraconazole at dosages of 2.5 or 10
      mg/kg and above. In contrast, the other three strains resistant to 8 mg/L
      itraconazole in vitro were refractory to the therapy, even at the highest
      itraconazole dosage (40 mg/kg). Closely similar in vivo data were obtained with
      the oral itraconazole therapy. The effective doses of the two itraconazole
      formulations increased with increasing itraconazole MICs for the infecting
      strains. CONCLUSIONS: The in vivo efficacy of intravenous and oral itraconazole
      correlated with the in vitro susceptibility data.

PMID- 21172783
TI  - Emergence of fluoroquinolone-resistant Streptococcus pyogenes in Japan by a point
      mutation leading to a new amino acid substitution.
AB  - OBJECTIVES: Streptococcus pyogenes causes various diseases in humans. While the
      prevalence of fluoroquinolone-resistant S. pyogenes isolates has been increasing
      since 2000 in the USA and Europe, it has remained very low in Japan. We isolated
      a fluoroquinolone-resistant S. pyogenes strain and analysed its genetics.
      METHODS: TU-296, a strain of S. pyogenes resistant to levofloxacin (MIC 16 mg/L),
      was isolated from the throat of a patient in their thirties with pharyngitis in
      autumn 2007. We carried out susceptibility tests for various antimicrobial agents
      and PCR analysis of the genes gyrA, gyrB, parC and parE in the quinolone
      resistance-determining region, followed by sequencing of the PCR products to find
      mutation(s) and the resulting amino acid substitution(s). We then sequenced the
      PCR product of the emm gene and determined the emm genotype. RESULTS: S. pyogenes
      TU-296 was found to have the following mutations and amino acid substitutions:
      adenine 476 to cytosine in gyrA and cytosine 367 to thymine in parC, resulting in
      Glu-85->Ala in GyrA and Ser-79->Phe in ParC. The genotype of the isolate was
      emm11. CONCLUSIONS: Amino acid substitutions in fluoroquinolone-resistant S.
      pyogenes have already been reported from Europe and the USA, including Ser-81
      >Phe or Tyr and Met-99->Leu in GyrA, as well as Ser-79->Phe, Tyr or Ala and
      others in ParC. Numerous point mutations were found in parC and parE of S.
      pyogenes TU-296. In addition, a new amino acid substitution was detected (Glu-85
      >Ala in GyrA). To our knowledge, there have been no previous reports of this
      substitution in a clinical isolate of S. pyogenes.

PMID- 21172784
TI  - Secular trends of antibacterial prescribing in UK paediatric primary care.
AB  - BACKGROUND: Resistance to antibacterial drugs can be contained by judicious
      prescribing. In particular, the use of these drugs in children requires ongoing
      surveillance. While there was a decline in antibacterial prescribing in the UK
      during the 1990s, recent trends are less well known. OBJECTIVES: To describe
      antibiotic prescribing patterns and time trends in children in the UK over the
      last two decades. METHODS: We identified all children ages 0-19 years from 1993
      to 2007 and their antibiotic prescriptions from the General Practice Research
      Database. We used Poisson regression to estimate prescription rates considering
      the children's age and gender, calendar year and practice. RESULTS: The cohort
      included 1 751 645 children with 5 835 891 antibacterial prescriptions. The
      average prescription rate was 511 prescriptions per 1000 person-years [95%
      confidence interval (CI) 509-513]. As of 1995, the rate decreased to 419/1000
      person-years (95% CI 411-426) in 2000, then increased to 568/1000 person-years
      (95% CI 559-577) in 2007. Between 2000 and 2007, rates increased on average by
      4.3% (95% CI 3.7-5.0%) annually, amounting to an increase of 40.7% (95% CI 34.5
      47.2%) for all children. Rates were generally higher in girls, except for boys <5
      years. Broad-spectrum penicillins were most frequently prescribed; their rate
      increased on average by 4.6% annually (95% CI 4.0-5.3%) after 2000. This trend
      was similar in most classes of antibacterials. CONCLUSIONS: Antibacterial
      prescribing to outpatient children in the UK has been steadily increasing since
      2000, consistently for boys and girls, across all ages and antibacterial classes.

PMID- 21172785
TI  - Identification of NDM-1-producing Enterobacteriaceae in Norway.

PMID- 21172786
TI  - Pandemic H1N1 2009 influenza virus with the H275Y oseltamivir resistance
      neuraminidase mutation shows a small compromise in enzyme activity and viral
      fitness.
AB  - BACKGROUND: Resistance to the neuraminidase inhibitor oseltamivir can be
      conferred by a well-characterized mutation in the neuraminidase gene, H275Y. In
      human H1N1 viruses that circulated in the first years of the 21st century, this
      mutation carried a fitness cost and resistant viruses were rare. During the 2007
      08 influenza season, oseltamivir-resistant viruses of H1N1 phenotype emerged and
      predominated. March 2009 saw the emergence of a novel H1N1 influenza pandemic. We
      examined whether the H275Y mutation affected neuraminidase enzyme activity or
      replication of the pandemic influenza virus. METHODS: Using reverse genetics we
      engineered the H275Y mutation into the neuraminidase of a 2009 pandemic H1N1
      virus and assessed the ability of this enzyme to desialylate mono- and
      multivalent substrates. The growth kinetics of wild-type and mutant viruses were
      assessed in Madin-Darby canine kidney (MDCK) and fully differentiated human
      airway epithelial (HAE) cells. RESULTS: The presence of H275Y was associated with
      a 1.3-fold decrease in the affinity of the neuraminidase for a monovalent
      substrate and a 4-fold compromise in desialylation of multivalent substrate. This
      was associated with a fitness cost to viral replication in vitro, which only
      became apparent during competitive replication in the mucus-rich HAE culture
      system. CONCLUSIONS: The neuraminidase protein of pandemic influenza isolates
      tolerates the H275Y mutation and this mutation confers resistance to oseltamivir.
      However, unlike seasonal H1N1 viruses isolated since 2007, the mutation is not
      associated with any fitness advantage and thus is unlikely to predominate without
      further antigenic drift, compensating mutations or intense selection pressure.

PMID- 21172787
TI  - Management of invasive fungal infections: a role for polyenes.
AB  - The spectrum of invasive fungal infections (IFIs) continues to evolve with the
      emergence of rare and resistant fungal pathogens. Clinicians are faced with
      difficult diagnostic and treatment challenges in the management of
      immunocompromised patients at high risk of developing IFIs. Early and appropriate
      antifungal therapy is essential for a successful outcome when treating invasive
      mycoses. The armamentarium of antifungal drugs continues to grow; the three main
      classes of commonly administered drugs are the polyenes, azoles and
      echinocandins. The newer triazoles and the echinocandins have changed primary
      treatment options for some fungal infections, such as aspergillosis and
      candidiasis. However, despite their toxic potential, the oldest antifungal drugs,
      polyenes, remain useful in the treatment of IFIs because of their broad-spectrum
      activity, low rates of resistance and established clinical record, particularly
      in immunocompromised patients with breakthrough fungal infections. This review
      highlights important issues in the treatment of IFIs for consideration by
      clinicians.

PMID- 21172789
TI  - Efficacy and safety of nucleoside reverse transcriptase inhibitor-sparing salvage
      therapy for multidrug-resistant HIV-1 infection based on new-class and new
      generation antiretrovirals.
AB  - BACKGROUND: The advent of new antiretrovirals has expanded the therapeutic
      options for multiple drug-resistant HIV-1 infection. The role of recycled
      nucleoside reverse transcriptase inhibitors (NRTIs) in this scenario remains
      uncertain. METHODS: Observational study of 122 consecutive patients with prior
      triple-class failure and multidrug-resistant HIV infection who started a salvage
      regimen with at least three of the new antiretrovirals darunavir, etravirine,
      raltegravir and maraviroc. Virological, immunological and clinical outcomes were
      compared according to the inclusion or not of NRTIs in the regimen, after 48
      weeks of follow-up. RESULTS: All patients received at least two and 65% received
      three fully active drugs in the salvage regimen. In 63 patients recycled NRTIs
      were added to new drugs (NRTI-containing group) and 59 patients did not receive
      NRTIs (NRTI-sparing group). Both groups were comparable at baseline regarding the
      number of prior failures, resistance profile, CD4 cell count and HIV plasma viral
      load. The rates of HIV-1 RNA suppression below 50 copies/mL at week 48 (intent-to
      treat analysis) were similar in the two groups: 46/59 [78%, 95% confidence
      interval (CI) 67%-88%] in the NRTI-sparing group and 49/63 (78%, 95% CI 67%-88%)
      in the NRTI-containing group. No significant differences were found in CD4 cell
      count increases. Drug-related adverse events leading to drug discontinuations
      only occurred in the NRTI-containing group (5 of 63, NRTI-related in 3 cases).
      CONCLUSIONS: The addition of NRTIs with reduced activity, according to genotypic
      resistance tests, does not seem to improve the efficacy of salvage regimens
      containing three of the new antiretrovirals in patients with multidrug-resistant
      HIV-1 infection.

PMID- 21172788
TI  - Significant ecological impact on the progression of fluoroquinolone resistance in
      Escherichia coli with increased community use of moxifloxacin, levofloxacin and
      amoxicillin/clavulanic acid.
AB  - OBJECTIVES: To determine trends in ciprofloxacin resistance and co-resistance to
      other antibiotic classes in blood isolates of Escherichia coli, and to
      investigate if there is an ecological relationship to the community use of
      fluoroquinolones and other antibiotics. METHODS: Forty-two Spanish hospitals of
      the European Antimicrobial Resistance Surveillance Network collected
      ciprofloxacin and other antibiotic susceptibility data for non-duplicate
      consecutive E. coli isolates from patients with bacteraemia between 2001 and
      2009. The nationwide ambulatory use of antibiotics between 1997 and 2008 was
      determined by WHO methods, and the co-evolution of both parameters was further
      analysed. RESULTS: Of the 28 307 E. coli blood isolates, 27.9% were ciprofloxacin
      non-susceptible (CIPNS), increasing from 17.6% in 2001 to 32.7% in 2009. A
      continuous increase was observed between CIPNS and other resistances, including
      cephalosporin resistance due to the production of extended-spectrum beta
      lactamases (ESBLs) and non-susceptibility to both amoxicillin/clavulanic acid and
      tobramycin. Although the total use of antibiotics did not increase, community use
      of levofloxacin, moxifloxacin and amoxicillin/clavulanic acid increased by
      307.2%, 62.6% and 70.1%, respectively. Yearly rates of CIPNS E. coli strongly
      correlated with the use of levofloxacin, moxifloxacin and amoxicillin/clavulanic
      acid (r(2 )> 0.80; P < 0.005 in all cases). CONCLUSIONS: The rapid increase in
      CIPNS E. coli causing bacteraemia was closely related to the increase in
      resistance to amoxicillin/clavulanic acid, production of ESBLs and resistance to
      aminoglycosides. Community use of fluoroquinolones (mainly moxifloxacin and
      levofloxacin) and of amoxicillin/clavulanic acid represents a significant driver
      in the progression of fluoroquinolone resistance in bacteraemic E. coli.

PMID- 21172790
TI  - An evaluation of gentamicin susceptibility of Neisseria gonorrhoeae isolates in
      Europe.
AB  - OBJECTIVES: The emergence of decreased susceptibility to third-generation,
      extended-spectrum cephalosporins in Neisseria gonorrhoeae and associated
      treatment failures highlights the need to consider alternatives for future
      therapeutic use, such as gentamicin. METHODS: The three laboratories surveying
      gonococcal antimicrobial susceptibility as part of the European Network for
      Sexually Transmitted Infections Surveillance compared agar dilution and Etest to
      determine gentamicin MICs and performed the first survey of gentamicin
      susceptibility on 1366 gonococcal isolates from 17 European Union/European
      Economic Area (EU/EAA) countries in 2009. RESULTS: Sentinel surveillance of
      gentamicin susceptibility showed that 95% of European isolates were within a
      narrow MIC range (4-8 mg/L), with 79% showing an MIC of 8 mg/L. Most countries
      showed little variation, but wider MIC ranges were observed in Greece (1-16 mg/L)
      and France, Norway and Sweden (2-16 mg/L). While MICs for both methods generally
      differed by just one doubling dilution, they were lower by Etest. CONCLUSIONS:
      This is the first reported evidence that the European gonococcal population
      susceptibility to gentamicin is similar to that reported in other world regions.
      Clinical trials to evaluate the therapeutic efficacy of gentamicin may be
      warranted.

PMID- 21172791
TI  - Pharmacokinetics of plasma lopinavir/ritonavir following the administration of
      400/100 mg, 200/150 mg and 200/50 mg twice daily in HIV-negative volunteers.
AB  - OBJECTIVES: Data suggest that some licensed antiretroviral doses could be
      reduced. We assessed the safety, tolerability and pharmacokinetics of
      lopinavir/ritonavir at doses of 400/100, 200/150 and 200/50 mg twice daily in HIV
      negative volunteers (http://clinicaltrials.gov/ct2/show/NCT00985543). METHODS:
      Male and female volunteers were administered lopinavir/ritonavir at doses of
      400/100 mg (two lopinavir/ritonavir Meltrex 200/50 mg tablets, Regimen 1),
      200/150 mg (one Meltrex tablet, one 100 mg ritonavir capsule, Regimen 2) and
      200/50 mg (one Meltrex tablet, Regimen 3). Each dose was given twice daily for 7
      days sequentially, separated by a 7 day wash-out period. Lopinavir/ritonavir
      steady-state pharmacokinetics was assessed over 12 h at the end of each phase
      (days 7, 21 and 35). Pharmacokinetic parameters were compared using the 400/100
      mg twice daily dose as reference, by determining geometric mean ratios (GMRs) and
      90% confidence intervals. RESULTS: Twenty-two subjects (eight females) completed
      the study. Lopinavir AUC(0-12) (ng h/mL), C(max) (ng/mL) and the minimum
      concentration (C(trough)) (ng/mL) for the 400/100, 200/150 and 200/50 mg twice
      daily doses, respectively, were as follows: 99,599, 73,603 and 45,146; 11,965,
      8939 and 6404; and 5776, 4293 and 1749. Lopinavir pharmacokinetic parameters were
      significantly lower for Regimens 2 and 3: GMR (90% CI) AUC(0-12), 0.74 (0.65
      0.84) and 0.45 (0.40-0.51); C(max), 0.75 (0.66-0.85) and 0.54 (0.40-0.60); and
      C(trough), 0.74 (0.62-0.89) and 0.30 (0.25-0.36), respectively. All subjects
      taking the 400/100 and 200/150 mg twice daily doses, and 19 (86%) subjects taking
      200/50 mg twice daily had lopinavir concentrations above the suggested minimum
      effective concentration of 1000 ng/mL. CONCLUSIONS: These pharmacokinetic data
      show that therapeutic plasma concentrations of lopinavir can be achieved with
      200/150 mg of lopinavir/ritonavir twice daily (one Meltrex tablet and one 100 mg
      ritonavir capsule twice daily).

PMID- 21172792
TI  - The effects of work-related maternal risk factors on time to pregnancy, preterm
      birth and birth weight: the Generation R Study.
AB  - OBJECTIVE: To investigate the influence of maternal working conditions on
      fertility and pregnancy outcomes. METHODS: 8880 women were enrolled in a large
      prospective birth cohort during early (76%), mid (21%) or late pregnancy (3%)
      (61% participation). Complete questionnaire information was available for 6302
      women (71% response). Outcomes were prolonged time to pregnancy (TTP) (> 6
      months), preterm birth (< 37 weeks) and decreased birth weight (< 3000 g). Self
      reported exposure to chemical agents was based on a limited list of chemicals.
      Physical load questions concerned manual materials handling, prolonged sitting
      and long periods of standing. A job-exposure matrix (JEM) linked reported job
      title to workplace chemical exposure within jobs according to expert judgement.
      Associations between maternal occupational exposure and fertility and pregnancy
      outcomes, adjusted for age, education, minority, parity, smoking and alcohol use,
      were studied using logistic regression analysis. RESULTS: Women in jobs with
      regular handling of loads >= 5 kg had better fertility and pregnancy outcomes. No
      self-reported exposure to chemicals was associated with any outcomes and self
      assessments had very low reliability compared with JEM-based assessments. JEM
      based maternal occupational exposure to phthalates was associated with prolonged
      TTP (OR 2.16, 95% CI 1.02 to 4.57) and exposure to pesticides was associated with
      decreased birth weight (OR 2.42, 95% CI 1.10 to 5.34). The population
      attributable fractions were small at 0.7% for phthalates and 0.7% for pesticides.
      CONCLUSION: This birth cohort study presents evidence of health-based selection
      into the workforce and adverse effects of maternal occupational exposure to
      phthalates and pesticides on fertility and pregnancy outcomes.

PMID- 21172793
TI  - Saharan dust and daily mortality in Emilia-Romagna (Italy).
AB  - OBJECTIVE: To investigate the association between Saharan dust outbreaks and
      natural, cardiovascular and respiratory mortality. METHODS: A case-crossover
      design was adopted to assess the effects of Saharan dust days (SDD) on mortality
      in the Emilia-Romagna region of Italy. The population under study consisted of
      residents in the six main towns of the central-western part of the region who
      died between August 2002 and December 2006. The association of Saharan dust
      outbreaks and PM(10) concentration with mortality was estimated using conditional
      logistic regression, adjusted for apparent temperature, holidays, summer
      population decrease, flu epidemic weeks and heat wave days. The role of the
      interaction term between PM(10) and SDD was analysed to test for effect
      modification induced by SDD on the PM(10)-mortality concentration-response
      function. Separate estimates were undertaken for hot and cold seasons. RESULTS:
      We found some evidence of increased respiratory mortality for people aged 75 or
      older on SDD. Respiratory mortality increased by 22.0% (95% CI 4.0% to 43.1%) on
      the SDD in the whole year model and by 33.9% (8.4% to 65.4%) in the hot season
      model. Effects substantially attenuated for natural and cardiovascular mortality
      with ORs of 1.042 (95% CI 0.992 to 1.095) and 1.043 (95% CI 0.969 to 1.122),
      respectively. CONCLUSIONS: Our findings suggest an association between
      respiratory mortality in the elderly and Saharan dust outbreaks. We found no
      evidence of an effect modification of dust events on the concentration-response
      relationship between PM(10) and daily deaths. Further work should be carried out
      to clarify the mechanism of action.

PMID- 21172794
TI  - Mortality and end-stage renal disease incidence among dry cleaning workers.
AB  - OBJECTIVE: Perchloroethylene (PCE) is a known animal carcinogen and probable
      human carcinogen. Dry cleaning exposures, particularly PCE, are also associated
      with renal toxicity. The objective was to follow-up a cohort of dry cleaners to
      evaluate mortality and assess end-stage renal disease (ESRD) morbidity. METHODS:
      This study adds 8 years of mortality follow-up for 1704 dry cleaning workers in
      four cities. Employees eligible for inclusion worked for >=1 year before 1960 in
      a shop using PCE as the primary solvent. Life table analyses for mortality and
      ESRD morbidity were conducted. Only employees alive on 1 January 1977 were
      included in ESRD analyses. RESULTS: Overall cancer deaths were in significant
      excess in this cohort (standardised mortality ratio (SMR) 1.22, 95% CI 1.09 to
      1.36). Oesophageal, lung and tongue cancers had significant excesses of deaths.
      Oesophageal cancer risk was highest among those employed in a PCE-using shop for
      >=5 years with >=20 years' latency since first such employment. Deaths from non
      malignant underlying diseases of the stomach and duodenum were in significant
      excess. Hypertensive ESRD morbidity was significantly elevated in the entire
      cohort (standardised incidence ratio (SIR) 1.98, 95% CI 1.11 to 3.27), and among
      workers employed only in PCE-using dry cleaning shops for >=5 years. CONCLUSION:
      Employment in the dry cleaning industry and occupational exposure to PCE are
      associated with an increased risk for ESRD and for cancer at several sites. The
      employment duration findings for oesophageal cancer and hypertensive ESRD further
      support an association with PCE exposure instead of lifestyle or socioeconomic
      factors.

PMID- 21172795
TI  - Cardiac autonomic dysfunction from occupational exposure to polycyclic aromatic
      hydrocarbons.
AB  - OBJECTIVES: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been
      associated with cardiopulmonary mortality and cardiovascular events. This study
      investigated the association between a biological marker of PAH exposure,
      assessed by urinary 1-hydroxypyrene (1-OHP), and heart-rate variability in an
      occupational cohort of boilermakers. METHODS: Continuous 24 h monitoring of the
      ambulatory electrocardiogram (ECG) and pre- and postshift urinary 1-OHP were
      repeated over extended periods of the work week. Mixed-effects models were fitted
      for the 5 min SD of normal-to-normal intervals (SDNN) in relation to urinary 1
      OHP levels pre- and postworkshift on the day they wore the monitor, controlling
      for potential confounders. RESULTS: The authors found a significant decrease in 5
      min SDNN during work of -13.6% (95% CI -17.2% to -9.8%) per SD (0.53 MUg/g
      creatinine) increase in the next-morning preshift 1-OHP levels. The magnitude of
      reduction in 5 min SDNN was largest during the late night period after work and
      increased with each SD (0.46 MUg/g creatinine) increase in postshift 1-OHP
      levels. CONCLUSION: This is the first report providing evidence that occupational
      exposure to PAHs is associated with altered cardiac autonomic function. Acute
      exposure to PAHs may be an important predictor of cardiovascular disease risk in
      the work environment.

PMID- 21172796
TI  - Modelling the impact of a healthy diet on cardiovascular disease and cancer
      mortality.
AB  - BACKGROUND: Quantifying the potential health benefits of improvements in the
      nutritional quality of the average diet of a population would provide evidence
      for resource allocation between population-level interventions aimed at reducing
      chronic disease. METHODS: A model was built linking consumption of food
      components with biological risk factors (blood pressure, serum cholesterol and
      obesity) and subsequent mortality from coronary heart disease, stroke and cancer.
      Meta-analyses of individual-level studies that quantified the RR of increased
      consumption/increased risk factor level on disease outcomes were used to build
      the model. The sensitivity of the model to the results from the meta-analyses was
      assessed with Monte Carlo simulations. Country-specific estimates of current
      nutrient intake compared against dietary recommendations for the UK were used to
      demonstrate the model. RESULTS: Approximately 33 000 deaths per year would be
      avoided if UK dietary recommendations were met. The modelled reduction in deaths
      for coronary heart disease was 20 800 (95% credible interval 17 845-24 069), for
      stroke 5876 (3856-7364) and for cancer 6481 (4487-8353). Over 15 000 of the
      avoided deaths would be due to increased consumption of fruit and vegetables.
      CONCLUSIONS: The developed model estimates the impact of population-level dietary
      changes and is robust. Achieving UK dietary recommendations for fruit and
      vegetable consumption (five portions a day) would result in substantial health
      benefits-equivalent benefits would be achieved if salt intakes were lowered to
      3.5 g per day or saturated fat intakes were lowered to 3% of total energy.

PMID- 21172797
TI  - What public policies have been more effective in promoting rational prescription
      of drugs?

PMID- 21172798
TI  - Do bonding and bridging social capital have differential effects on self-rated
      health? A community based study in Japan.
AB  - BACKGROUND: Few studies have examined the potential difference in the
      relationship between bonding versus bridging social capital and health outcomes.
      We sought to examine the association between these different types of social
      capital and self-rated health in a population-based study. METHODS: In February
      2009, 4000 residents of Okayama City (aged 20-80 y) were randomly selected for a
      survey on social capital and health. The survey asked about participation in six
      different types of associations: Parents and Teachers Association, sports clubs,
      alumni associations, political campaign clubs, citizen's groups and community
      associations. We distinguished between bonding and bridging social capital by
      asking participants about their perceived homogeneity (with respect to gender,
      age and occupation) of the groups they belonged to. ORs and 95% CIs for poor
      health were calculated. RESULTS: Bridging social capital (ie, participation in
      groups involving people from a diversity of backgrounds) was inversely associated
      with poor health in both sexes and women appeared to benefit more than men.
      Compared to those who reported zero participation, high bridging social capital
      was associated with a reduced odds of poor health (OR 0.25, 95% CI 0.11 to 0.55)
      in women after controlling for demographic variables, socioeconomic status,
      smoking habit and overweight. By contrast, bonding social capital was not
      consistently associated with better health in either gender. CONCLUSIONS: The
      present study suggests that bonding and bridging social capital have differential
      associations with health and that the two forms of social capital need to be
      distinguished in considering interventions to promote health.

PMID- 21172799
TI  - Economic costs of health inequalities in the European Union.
AB  - BACKGROUND: In order to support the case for inter-sectoral policies to tackle
      health inequalities, the authors explored the economic costs of socioeconomic
      inequalities in health in the European Union (EU). METHODS: Using recent data on
      inequalities in self-assessed health and mortality covering most of the EU,
      health losses due to socioeconomic inequalities in health were calculated by
      applying a counterfactual scenario in which the health of those with lower
      secondary education or lower (roughly 50% of the population) would be improved to
      the average level of health of those with at least higher secondary education. We
      then calculated various economic effects of those health losses: healthcare
      costs, costs of social security schemes, losses to Gross Domestic Product (GDP)
      through reduced labour productivity and the monetary value of total losses in
      welfare. RESULTS: Inequality related losses to health amount to more than 700 000
      deaths per year and 33 million prevalent cases of ill health in the EU as a
      whole. These losses account for 20% of the total costs of healthcare and 15% of
      the total costs of social security benefits. Inequality related losses to health
      reduce labour productivity and take 1.4% off GDP each year. The monetary value of
      health inequality related welfare losses is estimated to be ?980 billion per year
      or 9.4% of GDP. CONCLUSION: Our results suggest that the economic costs of
      socioeconomic inequalities in health in Europe are substantial. As this is a
      first attempt at quantifying the economic implications of health inequalities,
      the estimates are surrounded by considerable uncertainty and further research is
      needed to reduce this. If our results are confirmed in further studies, the
      economic implications of health inequalities warrant significant investments in
      policies and interventions to reduce them.

PMID- 21172800
TI  - Tangled localization at the cortical division site of plant cells occurs by
      several mechanisms.
AB  - TANGLED (TAN) is the founding member of a family of plant-specific proteins
      required for correct orientation of the division plane. Arabidopsis thaliana TAN
      is localized before prophase until the end of cytokinesis at the cortical
      division site (CDS), where it appears to help guide the cytokinetic apparatus
      towards the cortex. We show that TAN is actively recruited to the CDS by distinct
      mechanisms before and after preprophase band (PPB) disassembly. Colocalization
      with the PPB is mediated by one region of TAN, whereas another region mediates
      its recruitment to the CDS during cytokinesis. This second region binds directly
      to POK1, a kinesin that is required for TAN localization. Although this region of
      TAN is recruited to the CDS during cytokinesis without first colocalizing with
      the PPB, pharmacological evidence indicates that the PPB is nevertheless required
      for both early and late localization of TAN at the CDS. Finally, we show that
      phosphatase activity is required for maintenance of early but not late TAN
      localization at the CDS. We propose a new model in which TAN is actively
      recruited to the CDS by several mechanisms, indicating that the CDS is
      dynamically modified from prophase through to the completion of cytokinesis.

PMID- 21172801
TI  - PML isoforms I and II participate in PML-dependent restriction of HSV-1
      replication.
AB  - Intrinsic antiviral resistance mediated by constitutively expressed cellular
      proteins is one arm of defence against virus infection. Promyelocytic leukaemia
      nuclear bodies (PML-NBs, also known as ND10) contribute to host restriction of
      herpes simplex virus type 1 (HSV-1) replication via mechanisms that are
      counteracted by viral regulatory protein ICP0. ND10 assembly is dependent on PML,
      which comprises several different isoforms, and depletion of all PML isoforms
      decreases cellular resistance to ICP0-null mutant HSV-1. We report that
      individual expression of PML isoforms I and II partially reverses the increase in
      ICP0-null mutant HSV-1 plaque formation that occurs in PML-depleted cells. This
      activity of PML isoform I is dependent on SUMO modification, its SUMO interaction
      motif (SIM), and each element of its TRIM domain. Detailed analysis revealed that
      the punctate foci formed by individual PML isoforms differ subtly from normal
      ND10 in terms of composition and/or Sp100 modification. Surprisingly, deletion of
      the SIM motif from PML isoform I resulted in increased colocalisation with other
      major ND10 components in cells lacking endogenous PML. Our observations suggest
      that complete functionality of PML is dependent on isoform-specific C-terminal
      sequences acting in concert.

PMID- 21172802
TI  - Aquaporin 0 enhances gap junction coupling via its cell adhesion function and
      interaction with connexin 50.
AB  - Both connexin 50 (Cx50) and aquaporin 0 (AQP0) have important roles in lens
      development and homeostasis, and their mutations are associated with human
      congenital cataracts. We have previously shown that Cx50 directly interacts with
      AQP0. Here, we demonstrate the importance of the Cx50 intracellular loop (IL)
      domain in mediating the interaction with AQP0 in the lens in vivo. AQP0
      significantly increased (~20-30%) the intercellular coupling and conductance of
      Cx50 gap junctions. However, this increase was not observed when the IL domain
      was replaced with those from other lens connexins. The Cx50-AQP0 interaction had
      no effect on Cx50 hemichannel function. A fusion protein containing three
      extracellular loop domains of AQP0 efficiently blocked the cell-to-cell adhesion
      of AQP0 and attenuated the stimulatory effect of AQP0 on Cx50 gap junction
      conductance. These data suggest that the specific interaction between Cx50 and
      AQP0 enhances the coupling of Cx50 gap junctions, but not hemichannels, through
      the cell adhesion function of AQP0. This result establishes a physiological role
      of AQP0 in the functional regulation of gap junction channels.

PMID- 21172803
TI  - Visualizing dynamic cytoplasmic forces with a compliance-matched FRET sensor.
AB  - Mechanical forces are ubiquitous modulators of cell activity but little is known
      about the mechanical stresses in the cell. Genetically encoded FRET-based force
      sensors now allow the measurement of local stress in specific host proteins in
      vivo in real time. For a minimally invasive probe, we designed one with a
      mechanical compliance matching that of many common cytoskeleton proteins. sstFRET
      is a cassette composed of Venus and Cerulean linked by a spectrin repeat. The
      stress sensitivity of the probe was measured in solution using DNA springs to
      push the donor and acceptor apart with 5-7 pN and this produced large changes in
      FRET. To measure cytoskeletal stress in vivo we inserted sstFRET into alpha
      actinin and expressed it in HEK and BAEC cells. Time-lapse imaging showed the
      presence of stress gradients in time and space, often uncorrelated with obvious
      changes in cell shape. The gradients could be rapidly relaxed by thrombin-induced
      cell contraction associated with inhibition of myosin II. The tension in actinin
      fluctuated rapidly (scale of seconds) illustrating a cytoskeleton in dynamic
      equilibrium. Stress in the cytoskeleton can be driven by macroscopic stresses
      applied to the cell. Using sstFRET as a tool to measure internal stress, we
      tested the prediction that osmotic pressure increases cytoskeletal stress. As
      predicted, hypotonic swelling increased the tension in actinin, confirming the
      model derived from AFM. Anisotonic stress also produced a novel transient (~2
      minutes) decrease in stress upon exposure to a hypotonic challenge, matched by a
      transient increase with hypertonic stress. This suggests that, at rest, the
      stress axis of actinin is not parallel to the stress axis of actin and that
      swelling can reorient actinin to lie more parallel where it can absorb a larger
      fraction of the total stress. Protein stress sensors are opening new perspectives
      in cell biology.

PMID- 21172804
TI  - Regulation of fragile sites expression in budding yeast by MEC1, RRM3 and
      hydroxyurea.
AB  - Fragile sites are specific loci within the genome that exhibit increased
      tendencies for chromosome breakage. They are conserved among mammals and are also
      found in lower eukaryotes including yeast and fly. Many conditions, including
      mutations and exogenous factors, contribute to fragile site expression, but the
      nature of interaction among them remains elusive. Here, we investigated this by
      examining the combined effects of rrm3Delta, mec1 and hydroxyurea (HU), three
      conditions that induce fragile sites, on expression of the replication slow zone
      (RSZ), a type of fragile site in budding yeast. Contrary to the expectation that
      each factor would contribute to fragile site expression in an independent manner,
      we show that rrm3Delta and high concentrations of HU suppressed RSZ expression in
      mec1-4ts cells. Further analyses revealed that rrm3Delta suppression occurs via
      promotion of Sml1 degradation, whereas HU suppresses RSZ via a premature
      commitment to inviability. Taken together, these observations demonstrate that:
      (1) the yeast genome contains different types of fragile site with regard to
      regulation of their expression, and (2) each fragile-site-inducing condition does
      not act independently, but can elicit a cellular response(s) that can
      paradoxically prevent the expression of a specific type(s) of fragile sites.

PMID- 21172805
TI  - TOX3 is a neuronal survival factor that induces transcription depending on the
      presence of CITED1 or phosphorylated CREB in the transcriptionally active
      complex.
AB  - TOX3 is a nuclear protein containing a high mobility group (HMG)-box domain,
      which regulates Ca(2+)-dependent transcription in neurons through interaction
      with the cAMP-response-element-binding protein (CREB). TOX3 appears to be
      associated with breast cancer susceptibility and was previously shown to be
      expressed downstream of a cytoprotective cascade together with CITED1, a
      transcriptional regulator that does not bind directly to DNA. In the present
      study we show that TOX3 is predominantly expressed in the brain, forms homodimers
      and interacts with CITED1. TOX3 overexpression protects neuronal cells from cell
      death caused by endoplasmic reticulum stress or BAX overexpression through the
      induction of anti-apoptotic transcripts and repression of pro-apoptotic
      transcripts, which correlates with enhanced transcription involving isolated
      estrogen-responsive elements and estrogen-responsive promoters. However, both
      functions cannot be inhibited with the anti-estrogen fulvestrant and are only
      attenuated by mutation of estrogen-responsive elements. TOX3 also interacts with
      native CREB and induces the CREB-responsive BCL-2 promoter, which can be
      inhibited by coexpression of CITED1. Coexpression of CREB, by contrast, abolishes
      TOX3-mediated transcription from the estrogen-responsive complement C3 promoter.
      Our results suggest that TOX3 can enhance transcriptional activation from
      different cytoprotective promoters and that this is dependent on the predominance
      of either phosphorylated CREB or CITED1 within the transcriptionally active
      complex.

PMID- 21172806
TI  - Stress-specific composition, assembly and kinetics of stress granules in
      Saccharomyces cerevisiae.
AB  - Eukaryotic cells respond to cellular stresses by the inhibition of translation
      and the accumulation of mRNAs in cytoplasmic RNA-protein (ribonucleoprotein)
      granules termed stress granules and P-bodies. An unresolved issue is how
      different stresses affect formation of messenger RNP (mRNP) granules. In the
      present study, we examine how sodium azide (NaN(3)), which inhibits mitochondrial
      respiration, affects formation of mRNP granules as compared with glucose
      deprivation in budding yeast. We observed that NaN(3) treatment inhibits
      translation and triggers formation of P-bodies and stress granules. The
      composition of stress granules induced by NaN(3) differs from that of glucose
      deprived cells by containing eukaryotic initiation factor (eIF)3, eIF4A/B, eIF5B
      and eIF1A proteins, and by lacking the heterogeneous nuclear RNP (hnRNP) protein
      Hrp1. Moreover, in contrast with glucose-deprived stress granules, NaN(3)
      triggered stress granules show different assembly rules, form faster and
      independently from P-bodies and dock or merge with P-bodies over time.
      Strikingly, addition of NaN(3) and glucose deprivation in combination, regardless
      of the order, always results in stress granules of a glucose deprivation nature,
      suggesting that both granules share an mRNP remodeling pathway. These results
      indicate that stress granule assembly, kinetics and composition in yeast can vary
      in a stress-specific manner, which we suggest reflects different rate-limiting
      steps in a common mRNP remodeling pathway.

PMID- 21172807
TI  - Loss of p38gamma MAPK induces pleiotropic mitotic defects and massive cell death.
AB  - The p38 mitogen-activated protein kinase (p38 MAPK) family, which is comprised of
      four protein isoforms, p38alpha, p38beta, p38gamma and p38delta, forms one of the
      key MAPK pathways. The p38 MAPKs are implicated in many cellular processes
      including inflammation, differentiation, cell growth, cell cycle and cell death.
      The function of p38 MAPKs in mitotic entry has been well established, but their
      role in mitotic progression has remained controversial. We identify p38gamma MAPK
      as a modulator of mitotic progression and mitotic cell death. In HeLa cells, loss
      of p38gamma results in multipolar spindle formation and chromosome misalignment,
      which induce a transient M phase arrest. The majority of p38gamma-depleted cells
      die at mitotic arrest or soon after abnormal exit from M-phase. We show that p38
      MAPKs are activated at the kinetochores and spindle poles throughout mitosis by
      kinase(s) that are stably bound to these structures. Finally, p38gamma is
      required for the normal kinetochore localization of polo-like kinase 1 (Plk1),
      and this contributes to the activity of the p38 MAPK pathway. Our data suggest a
      link between mitotic regulation and the p38 MAPK pathway, in which p38gamma
      prevents chromosomal instability and supports mitotic cell viability.

PMID- 21172808
TI  - Regulated Crb accumulation controls apical constriction and invagination in
      Drosophila tracheal cells.
AB  - Many epithelial tissues undergo extensive remodelling during morphogenesis. How
      their epithelial features, such as apicobasal polarity or adhesion, are
      maintained and remodelled and how adhesion and polarity proteins contribute to
      morphogenesis are two important questions in development. Here, we approach these
      issues by investigating the role of the apical determinant protein Crumbs (Crb)
      during the morphogenesis of the embryonic Drosophila tracheal system. Crb
      accumulates differentially throughout tracheal development and is required for
      different tracheal events. The earliest requirement for Crb is for tracheal
      invagination, which is preceded by an enhanced accumulation of Crb in the
      invagination domain. There, Crb, acting in parallel with the epidermal growth
      factor receptor (Egfr) pathway, is required for tracheal cell apical constriction
      and for organising an actomyosin complex, which we propose is mediated by Crb
      recruitment of moesin (Moe). The ability of a Crb isoform unable to rescue
      polarity in crb mutants to otherwise rescue their invagination phenotype, and the
      converse inability of a FERM-binding domain mutant Crb to rescue faulty
      invagination, support our hypothesis that it is the absence of Crb-dependent Moe
      enrichment, and not the polarity defect, that mainly underlies the crb
      invagination phenotype. This hypothesis is supported by the phenotype of lethal
      giant larvae (lgl); crb double mutants. These results unveil a link between Crb
      and the organisation of the actin cytoskeleton during morphogenesis.

PMID- 21172809
TI  - Taking the very first steps: from polarity to axial domains in the early
      Arabidopsis embryo.
AB  - Arabidopsis embryos follow a predictable sequence of cell divisions, facilitating
      a genetic analysis of their early development. Both asymmetric divisions and cell
      to-cell communication are probably involved in generating specific gene
      expression domains along the main axis within the first few division cycles. The
      function of these domains is not always understood, but recent work suggests that
      they may serve as a basis for organizing polar auxin flux. Auxin acts as systemic
      signal throughout the life cycle and, in the embryo, has been demonstrated to
      direct formation of the main axis and root initiation at the globular stage. At
      about the same time, root versus shoot fates are imposed on the incipient
      meristems by the expression of antagonistic regulators at opposite poles of the
      embryo. Some of the key features of the embryonic patterning process have emerged
      over the past few years and may provide the elements of a coherent conceptual
      framework.

PMID- 21172810
TI  - Small RNA activity and function in angiosperm gametophytes.
AB  - Small non-coding RNAs are key post-transcriptional and transcriptional regulators
      of plant gene expression in angiosperm sporophytes. In recent years, gametophytic
      small RNAs have also been investigated, predominantly in Arabidopsis male
      gametophytes, revealing features in common with the sporophyte as well as some
      surprising differences. Transcriptomic and deep-sequencing studies confirm that
      multiple small RNA pathways operate in male gametophytes, with over 100 miRNAs
      detected throughout development. Trans-acting siRNA pathways that are associated
      with novel phased transcripts in pollen, and the nat-siRNA pathway have important
      roles in pollen maturation and gamete function. Moreover, a role for siRNA
      triggered silencing of transposable elements in male and female germ cells has
      been established, a feature in common with the role of piRNAs in animal
      germlines. Current evidence supports an integral role for small RNAs in
      angiosperm gametophyte development and it can be anticipated that novel small
      RNAs with significant roles in germline development and genome integrity await
      discovery.

PMID- 21172811
TI  - Related polymorphic F-box protein genes between haplotypes clustering in the BAC
      contig sequences around the S-RNase of Japanese pear.
AB  - Most fruit trees in the Rosaceae exhibit self-incompatibility, which is
      controlled by the pistil S gene, encoding a ribonuclease (S-RNase), and the
      pollen S gene at the S-locus. The pollen S in Prunus is an F-box protein gene
      (SLF/SFB) located near the S-RNase, but it has not been identified in Pyrus and
      Malus. In the Japanese pear, various F-box protein genes (PpSFBB(-alpha-gamma))
      linked to the S-RNase are proposed as the pollen S candidate. Two bacterial
      artificial chromosome (BAC) contigs around the S-RNase genes of Japanese pear
      were constructed, and 649 kb around S(4)-RNase and 378 kb around S(2)-RNase were
      sequenced. Six and 10 pollen-specific F-box protein genes (designated as PpSFBB(4
      u1-u4, 4-d1-d2) and PpSFBB(2-u1-u5,) (2-d1-d5), respectively) were found, but
      PpSFBB(4-alpha-gamma) and PpSFBB(2-gamma) were absent. The PpSFBB(4) genes showed
      66.2-93.1% amino acid identity with the PpSFBB(2) genes, which indicated
      clustering of related polymorphic F-box protein genes between haplotypes near the
      S-RNase of the Japanese pear. Phylogenetic analysis classified 36 F-box protein
      genes of Pyrus and Malus into two major groups (I and II), and also generated
      gene pairs of PpSFBB genes and PpSFBB/Malus F-box protein genes. Group I
      consisted of gene pairs with 76.3-94.9% identity, while group II consisted of
      gene pairs with higher identities (>92%) than group I. This grouping suggests
      that less polymorphic PpSFBB genes in group II are non-S pollen genes and that
      the pollen S candidates are included in the group I PpSFBB genes.

PMID- 21172812
TI  - Silicon enhances suberization and lignification in roots of rice (Oryza sativa).
AB  - The beneficial element silicon (Si) may affect radial oxygen loss (ROL) of rice
      roots depending on suberization of the exodermis and lignification of
      sclerenchyma. Thus, the effect of Si nutrition on the oxidation power of rice
      roots, suberization and lignification was examined. In addition, Si-induced
      alterations of the transcript levels of 265 genes related to suberin and lignin
      synthesis were studied by custom-made microarray and quantitative Real Time-PCR.
      Without Si supply, the oxidation zone of 12 cm long adventitious roots extended
      along the entire root length but with Si supply the oxidation zone was restricted
      to 5 cm behind the root tip. This pattern coincided with enhanced suberization of
      the exodermis and lignification of sclerenchyma by Si supply. Suberization of the
      exodermis started, with and without Si supply, at 4-5 cm and 8-9 cm distance from
      the root tip (drt), respectively. Si significantly increased transcript abundance
      of 12 genes, while two genes had a reduced transcript level. A gene coding for a
      leucine-rich repeat protein exhibited a 25-fold higher transcript level with Si
      nutrition. Physiological, histochemical, and molecular-biological data showing
      that Si has an active impact on rice root anatomy and gene transcription is
      presented here.

PMID- 21172813
TI  - RCD1 and SRO1 are necessary to maintain meristematic fate in Arabidopsis
      thaliana.
AB  - The radical-induced cell death1 and similar to RCD ONE1 genes of Arabidopsis
      thaliana encode members of the poly(ADP-ribose) polymerase (PARP) superfamily and
      have pleiotropic functions in development and abiotic stress response. In order
      to begin to understand the developmental and molecular bases of the defects seen
      in rcd1-3; sro1-1 plants, this study used the root as a model. Double mutant
      roots are short and display abnormally organized root apical meristems. However,
      acquisition of most cell fates within the root is not significantly disrupted.
      The identity of the quiescent centre is compromised, the zone of cell division is
      smaller than in wild-type roots and abnormal divisions are common, suggesting
      that RCD1 and SRO1 are necessary to maintain cells in a division-competent state
      and to regulate division plane placement. In addition, differentiation of several
      cell types is disrupted in rcd1-3; sro1-1 roots and shoots, demonstrating that
      RCD1 and SRO1 are also necessary for proper cell differentiation. Based on the
      data shown in this article and previous work, we hypothesize that RCD1 and SRO1
      are involved in redox control and, in their absence, an altered redox balance
      leads to abnormal development.

PMID- 21172814
TI  - New perspectives on glutamine synthetase in grasses.
AB  - Members of the glutamine synthetase (GS) gene family have now been characterized
      in many crop species such as wheat, rice, and maize. Studies have shown that
      cytosolic GS isoforms are involved in nitrogen remobilization during leaf
      senescence and emphasized a role in seed production particularly in small grain
      crop species. Data from the sequencing of genomes for model crops and expressed
      sequence tag (EST) libraries from non-model species have strengthened the idea
      that the cytosolic GS genes are organized in three functionally and
      phylogenetically conserved subfamilies. Using a bioinformatic approach, the
      considerable publicly available information on high throughput gene expression
      was mined to search for genes having patterns of expression similar to GS.
      Interesting new hypotheses have emerged from searching for co-expressed genes
      across multiple unfiltered experimental data sets in rice. This approach should
      inform new experimental designs and studies to explore the regulation of the GS
      gene family further. It is expected that understanding the regulation of GS under
      varied climatic conditions will emerge as an important new area considering the
      results from recent studies that have shown nitrogen assimilation to be critical
      to plant acclimation to high CO(2) concentrations.

PMID- 21172816
TI  - Photosynthesis and drought: can we make metabolic connections from available
      data?
AB  - Photosynthesis is one of the key processes to be affected by water deficits, via
      decreased CO2 diffusion to the chloroplast and metabolic constraints. The
      relative impact of those limitations varies with the intensity of the stress, the
      occurrence (or not) of superimposed stresses, and the species we are dealing
      with. Total plant carbon uptake is further reduced due to the concomitant or even
      earlier inhibition of growth. Leaf carbohydrate status, altered directly by water
      deficits or indirectly (via decreased growth), acts as a metabolic signal
      although its role is not totally clear. Other relevant signals acting under water
      deficits comprise: abscisic acid (ABA), with an impact on stomatal aperture and
      the regulation at the transcription level of a large number of genes related to
      plant stress response; other hormones that act either concurrently
      (brassinosteroids, jasmonates, and salycilic acid) or antagonistically (auxin,
      cytokinin, or ethylene) with ABA; and redox control of the energy balance of
      photosynthetic cells deprived of CO2 by stomatal closure. In an attempt to
      systematize current knowledge on the complex network of interactions and
      regulation of photosynthesis in plants subjected to water deficits, a meta
      analysis has been performed covering >450 papers published in the last 15 years.
      This analysis shows the interplay of sugars, reactive oxygen species (ROS), and
      hormones with photosynthetic responses to drought, involving many metabolic
      events. However, more significantly it highlights (i) how fragmented and often
      non-comparable the results are and (ii) how hard it is to relate molecular events
      to plant physiological status, namely photosynthetic activity, and to stress
      intensity. Indeed, the same data set usually does not integrate these different
      levels of analysis. Considering these limitations, it was hard to find a general
      trend, particularly concerning molecular responses to drought, with the exception
      of the genes ABI1 and ABI3. These genes, irrespective of the stress type (acute
      versus chronic) and intensity, show a similar response to water shortage in the
      two plant systems analysed (Arabidopsis and barley). Both are associated with ABA
      mediated metabolic responses to stress and the regulation of stomatal aperture.
      Under drought, ABI1 transcription is up-regulated while ABI3 is usually down
      regulated. Recently ABI3 has been hypothesized to be essential for successful
      drought recovery.

PMID- 21172815
TI  - Mechanical wounding induces a nitrosative stress by down-regulation of GSNO
      reductase and an increase in S-nitrosothiols in sunflower (Helianthus annuus)
      seedlings.
AB  - Nitric oxide (NO) and related molecules such as peroxynitrite, S
      nitrosoglutathione (GSNO), and nitrotyrosine, among others, are involved in
      physiological processes as well in the mechanisms of response to stress
      conditions. In sunflower seedlings exposed to five different adverse
      environmental conditions (low temperature, mechanical wounding, high light
      intensity, continuous light, and continuous darkness), key components of the
      metabolism of reactive nitrogen species (RNS) and reactive oxygen species (ROS),
      including the enzyme activities L-arginine-dependent nitric oxide synthase (NOS),
      S-nitrosogluthathione reductase (GSNOR), nitrate reductase (NR), catalase, and
      superoxide dismutase, the content of lipid hydroperoxide, hydrogen peroxide, S
      nitrosothiols (SNOs), the cellular level of NO, GSNO, and GSNOR, and protein
      tyrosine nitration [nitrotyrosine (NO(2)-Tyr)] were analysed. Among the stress
      conditions studied, mechanical wounding was the only one that caused a down
      regulation of NOS and GSNOR activities, which in turn provoked an accumulation of
      SNOs. The analyses of the cellular content of NO, GSNO, GSNOR, and NO(2)-Tyr by
      confocal laser scanning microscopy confirmed these biochemical data. Therefore,
      it is proposed that mechanical wounding triggers the accumulation of SNOs,
      specifically GSNO, due to a down-regulation of GSNOR activity, while NO(2)-Tyr
      increases. Consequently a process of nitrosative stress is induced in sunflower
      seedlings and SNOs constitute a new wound signal in plants.

PMID- 21172817
TI  - COPII-mediated vesicle formation at a glance.

PMID- 21172818
TI  - Lipid map of the mammalian cell.

PMID- 21172819
TI  - Mechanisms of mechanical signaling in development and disease.
AB  - The responses of cells to chemical signals are relatively well characterized and
      understood. Cells also respond to mechanical signals in the form of externally
      applied force and forces generated by cell-matrix and cell-cell contacts. Many
      features of cell function that are generally considered to be under the control
      of chemical stimuli, such as motility, proliferation, differentiation and
      survival, can also be altered by changes in the stiffness of the substrate to
      which the cells are adhered, even when their chemical environment remains
      unchanged. Many examples from clinical and whole animal studies have shown that
      changes in tissue stiffness are related to specific disease characteristics and
      that efforts to restore normal tissue mechanics have the potential to reverse or
      prevent cell dysfunction and disease. How cells detect stiffness is largely
      unknown, but the cellular structures that measure stiffness and the general
      principles by which they work are beginning to be revealed. This Commentary
      highlights selected recent reports of mechanical signaling during disease
      development, discusses open questions regarding the physical mechanisms by which
      cells sense stiffness, and examines the relationship between studies in vitro on
      flat substrates and the more complex three-dimensional setting in vivo.

PMID- 21172820
TI  - TbetaRI/Alk5-independent TbetaRII signaling to ERK1/2 in human skin cells
      according to distinct levels of TbetaRII expression.
AB  - TGFbeta binding to the TGFbeta receptor (TbetaR) activates R-Smad-dependent
      pathways, such as Smad2/3, and R-Smad-independent pathways, such as ERK1/2. The
      mechanism of the TGFbeta-TbetaRII-TbetaRI-Smad2/3 pathway is established;
      however, it is not known how TGFbeta activates ERK1/2. We show here that although
      TGFbeta equally activated Smad2/3 in all cells, it selectively activated ERK1/2
      in dermal cells and inhibited ERK1/2 in epidermal cells. These opposite effects
      correlated with the distinct expression levels of TbetaRII, which are 7- to 18
      fold higher in dermal cells than in epidermal cells. Reduction of TbetaRII
      expression in dermal cells abolished TGFbeta-stimulated ERK1/2 activation.
      Upregulation of TbetaRII expression in epidermal cells to a similar level as that
      in dermal cells switched TGFbeta-induced ERK1/2 inhibition to ERK1/2 activation.
      More intriguingly, in contrast to the equal importance of TbetaRII in mediating
      TGFbeta signaling to both Smad2/3 and ERK1/2, knockdown of TbetaRI/Alk5 blocked
      activation of only Smad2/3, not ERK1/2, in dermal cells. Similarly, expression of
      the constitutively activated TbetaRI-TD kinase activated only Smad2/3 and not
      ERK1/2 in epidermal cells. This study provides an explanation for why TGFbeta
      selectively activates ERK1/2 in certain cell types and direct evidence for
      TbetaRI-independent TbetaRII signaling to a R-Smad-independent pathway.

PMID- 21172821
TI  - A hidden incoherent switch regulates RCAN1 in the calcineurin-NFAT signaling
      network.
AB  - Regulator of calcineurin 1 (RCAN1) is a key regulator of the calcineurin-NFAT
      signaling network in organisms ranging from yeast to human, but its functional
      role is still under debate because different roles of RCAN1 have been suggested
      under various experimental conditions. To elucidate the mechanisms underlying the
      RCAN1 regulatory system, we used a systems approach by combining single-cell
      experimentation with in silico simulations. In particular, we found that the
      nuclear export of GSK3beta, which switches on the facilitative role of RCAN1 in
      the calcineurin-NFAT signaling pathway, is promoted by PI3K signaling. Based on
      this, along with integrated information from previous experiments, we developed a
      mathematical model in which the functional role of RCAN1 changes in a dose
      dependent manner: RCAN1 functions as an inhibitor when its levels are low, but as
      a facilitator when its levels are high. Furthermore, we identified a hidden
      incoherent regulation switch that mediates this role change, which entails
      negative regulation through RCAN1 binding to calcineurin and positive regulation
      through sequential phosphorylation of RCAN1.

PMID- 21172823
TI  - An endophilin-dynamin complex promotes budding of clathrin-coated vesicles during
      synaptic vesicle recycling.
AB  - Clathrin-mediated vesicle recycling in synapses is maintained by a unique set of
      endocytic proteins and interactions. We show that endophilin localizes in the
      vesicle pool at rest and in spirals at the necks of clathrin-coated pits (CCPs)
      during activity in lamprey synapses. Endophilin and dynamin colocalize at the
      base of the clathrin coat. Protein spirals composed of these proteins on lipid
      tubes in vitro have a pitch similar to the one observed at necks of CCPs in
      living synapses, and lipid tubules are thinner than those formed by dynamin
      alone. Tubulation efficiency and the amount of dynamin recruited to lipid tubes
      are dramatically increased in the presence of endophilin. Blocking the
      interactions of the endophilin SH3 domain in situ reduces dynamin accumulation at
      the neck and prevents the formation of elongated necks observed in the presence
      of GTPgammaS. Therefore, endophilin recruits dynamin to a restricted part of the
      CCP neck, forming a complex, which promotes budding of new synaptic vesicles.

PMID- 21172824
TI  - Morphological, genetic, and chromosomal variation at a small spatial scale within
      a mosaic hybrid zone of the grasshopper Dichroplus pratensis Bruner (Acrididae).
AB  - Hybrid zones are regions where genetically different populations meet and mate,
      resulting in offspring of mixed characteristics. In organisms with limited
      dispersal, such as melanopline grasshoppers, hybrid zones can occur at small
      spatial scales (i.e., <500 m). We assessed levels of morphological, chromosomal,
      and molecular variability in adult males of the grasshopper Dichroplus pratensis
      Bruner (N = 137 males, 188 females) collected at 12 sites within a mosaic hybrid
      zone in a heterogeneous environment in Sierra de la Ventana, Argentina. In this
      hybrid zone, 2 Robertsonian chromosomal races, polymorphic for different centric
      fusions, meet (the "Northern race" at low altitudes and the "Southern race" at
      higher altitudes), forming hybrids that show monobrachial homologies during
      meiosis. High morphometric variation in 6 traits was revealed among grasshoppers
      of both sexes, with male body size positively and significantly correlated with
      increasing altitude. Frequency of Robertsonian fusions characteristic of the
      Southern race increased significantly with altitude. Moreover, fusion frequencies
      covaried between samples. Considerable genetic variation was revealed by random
      amplification of polymorphic DNA markers, with heterozygosity ranging from 0.3477
      to 0.3745. Insects from low-altitude and high-altitude populations showed
      significant genetic differentiation, as indicated by F(ST) values. The proposed
      model for D. pratensis, involving the generation and maintenance by chromosomal
      fusions, of gene complexes adaptive in different environments, could explain the
      observed clinal patterns within the contact zone.

PMID- 21172822
TI  - Depletion of nuclear actin is a key mediator of quiescence in epithelial cells.
AB  - Functional differentiation is orchestrated by precise growth-regulatory controls
      conveyed by the tissue microenvironment. Cues from laminin 111 (LN1) lower
      transcription and suppress mammary epithelial cell growth in culture, but how LN1
      induces quiescence is unknown. Recent literature points to involvement of nuclear
      beta-actin in transcriptional regulation. Here, we show that quiescence induced
      by growth factor withdrawal, or LN1 addition, rapidly decreases nuclear beta
      actin. LN1, but not other extracellular matrix (ECM) molecules, decreases the
      levels of nuclear beta-actin and destabilizes RNA polymerase (RNA Pol) II and III
      binding to transcription sites, leading to a dramatic drop in transcription and
      DNA synthesis. Constitutive overexpression of globular beta-actin in the nucleus
      reverses the effect of LN1 on transcription and RNA Pol II association and
      prevents the cells from becoming quiescent in the presence of LN1. The
      physiological relevance of our findings was verified by identifying a clear
      spatial separation of LN1 and beta-actin in developing mammary end buds. These
      data indicate a novel role for nuclear beta-actin in growth arrest of epithelial
      cells and underscore the importance of the integrity of the basement membrane in
      homeostasis.

PMID- 21172825
TI  - Sweet drinks are made of this: conservation genetics of an endemic palm species
      from the Dominican Republic.
AB  - Pseudophoenix ekmanii is a threatened palm species endemic to the Dominican
      Republic. Sap from trees is extracted to make a local drink; once they are tapped
      the individual usually dies. Plants are also illegally harvested for the nursery
      trade and destroyed by poachers hunting the endemic and threatened Hispaniolan
      parrot. We used 7 DNA microsatellite markers to assist land managers in
      developing conservation strategies for this palm. We sampled 4 populations along
      the known distribution range of this species (3 populations from the mainland and
      1 from the small island of Isla Beata), for a total sample of n = 104. We found
      strong evidence for genetic drift, inbreeding, and moderate gene flow (i.e., all
      populations had at least 4 loci that were not in Hardy-Weinberg equilibrium, at
      least 9 loci pairs were in linkage disequilibrium, the pairwise F(ST) values
      ranged from 0.069 to 0.266, and had positive F(IS) values). Data supported an
      isolation-by-distance model, and cluster analyses based on genetic distances
      resolved 2 groups that match a north-south split. The population from Isla Beata
      had the lowest levels of genetic diversity and was the only one in which we found
      pairs of individuals with identical shared multilocus genotypes.

PMID- 21172827
TI  - Molecular evolution of a Y chromosome to autosome gene duplication in Drosophila.
AB  - In contrast to the rest of the genome, the Y chromosome is restricted to males
      and lacks recombination. As a result, Y chromosomes are unable to respond
      efficiently to selection, and newly formed Y chromosomes degenerate until few
      genes remain. The rapid loss of genes from newly formed Y chromosomes has been
      well studied, but gene loss from highly degenerate Y chromosomes has only
      recently received attention. Here, we identify and characterize a Y to autosome
      duplication of the male fertility gene kl-5 that occurred during the evolution of
      the testacea group species of Drosophila. The duplication was likely DNA based,
      as other Y-linked genes remain on the Y chromosome, the locations of introns are
      conserved, and expression analyses suggest that regulatory elements remain
      linked. Genetic mapping reveals that the autosomal copy of kl-5 resides on the
      dot chromosome, a tiny autosome with strongly suppressed recombination. Molecular
      evolutionary analyses show that autosomal copies of kl-5 have reduced
      polymorphism and little recombination. Importantly, the rate of protein evolution
      of kl-5 has increased significantly in lineages where it is on the dot versus Y
      linked. Further analyses suggest this pattern is a consequence of relaxed
      purifying selection, rather than adaptive evolution. Thus, although the initial
      fixation of the kl-5 duplication may have been advantageous, slightly deleterious
      mutations have accumulated in the dot-linked copies of kl-5 faster than in the Y
      linked copies. Because the dot chromosome contains seven times more genes than
      the Y and is exposed to selection in both males and females, these results
      suggest that the dot suffers the deleterious effects of genetic linkage to more
      selective targets compared with the Y chromosome. Thus, a highly degenerate Y
      chromosome may not be the worst environment in the genome, as is generally
      thought, but may in fact be protected from the accumulation of deleterious
      mutations relative to other nonrecombining regions that contain more genes.

PMID- 21172828
TI  - Recovering population parameters from a single gene genealogy: an unbiased
      estimator of the growth rate.
AB  - We show that the number of lineages ancestral to a sample, as a function of time
      back into the past, which we call the number of lineages as a function of time
      (NLFT), is a nearly deterministic property of large-sample gene genealogies. We
      obtain analytic expressions for the NLFT for both constant-sized and
      exponentially growing populations. The low level of stochastic variation
      associated with the NLFT of a large sample suggests using the NLFT to make
      estimates of population parameters. Based on this, we develop a new computational
      method of inferring the size and growth rate of a population from a large sample
      of DNA sequences at a single locus. We apply our method first to a sample of
      1,212 mitochondrial DNA (mtDNA) sequences from China, confirming a pattern of
      recent population growth previously identified using other techniques, but with
      much smaller confidence intervals for past population sizes due to the low
      variation of the NLFT. We further analyze a set of 63 mtDNA sequences from blue
      whales (BWs), concluding that the population grew in the past. This calls for
      reevaluation of previous studies that were based on the assumption that the BW
      population was fixed.

PMID- 21172826
TI  - Population genomics of transposable elements in Drosophila melanogaster.
AB  - Transposable elements (TEs) are the primary contributors to the genome bulk in
      many organisms and are major players in genome evolution. A clear and thorough
      understanding of the population dynamics of TEs is therefore essential for full
      comprehension of the eukaryotic genome evolution and function. Although TEs in
      Drosophila melanogaster have received much attention, population dynamics of most
      TE families in this species remains entirely unexplored. It is not clear whether
      the same population processes can account for the population behaviors of all TEs
      in Drosophila or whether, as has been suggested previously, different orders
      behave according to very different rules. In this work, we analyzed population
      frequencies for a large number of individual TEs (755 TEs) in five North American
      and one sub-Saharan African D. melanogaster populations (75 strains in total).
      These TEs have been annotated in the reference D. melanogaster euchromatic genome
      and have been sampled from all three major orders (non-LTR, LTR, and TIR) and
      from all families with more than 20 TE copies (55 families in total). We find
      strong evidence that TEs in Drosophila across all orders and families are subject
      to purifying selection at the level of ectopic recombination. We showed that
      strength of this selection varies predictably with recombination rate, length of
      individual TEs, and copy number and length of other TEs in the same family.
      Importantly, these rules do not appear to vary across orders. Finally, we built a
      statistical model that considered only individual TE-level (such as the TE
      length) and family-level properties (such as the copy number) and were able to
      explain more than 40% of the variation in TE frequencies in D. melanogaster.

PMID- 21172829
TI  - Analysis of reptilian APOBEC1 suggests that RNA editing may not be its ancestral
      function.
AB  - The Activation Induced Deaminase (AID)/APOBEC family of deaminases targeting
      nucleic acids arose at the beginning of the vertebrate radiation and further
      expanded in mammals. Following an analysis of the available genomic data, we
      report the identification of the APOBEC5, a novel group of paralogues in
      tetrapods. Moreover, we find bona fide homologues of Apolipoprotein B Editing
      Complex 1 (APOBEC1) in the genomes of anole lizard and zebra finch, thus implying
      its appearance prior to the divergence of the amniotes. apolipoprotein B editing
      complex 1 (APOBEC1), in contrast with other AID/APOBECs acting on DNA, is an RNA
      editing enzyme that targets the transcript of Apolipoprotein B (ApoB), thereby
      causing the translation of a truncated form of the protein. 3'RACE experiments
      reveal a lizard APOBEC1-like molecule lacking a C-terminal region important for
      mammalian ApoB RNA editing. This observation pairs with the finding that lizard
      ApoB is not deaminated at the region corresponding to the mammalian site of
      editing. Similar to mammalian APOBEC1, the lizard protein is able to deaminate
      DNA in bacteria and shows a conserved mutational context. Although not precluding
      the possibility that lizard APOBEC1 acts on unknown mRNA targets, these findings
      suggest that its ability to target DNA predates its role in RNA editing.

PMID- 21172830
TI  - Changes in Rubisco kinetics during the evolution of C4 photosynthesis in Flaveria
      (Asteraceae) are associated with positive selection on genes encoding the enzyme.
AB  - Rubisco, the primary photosynthetic carboxylase, evolved 3-4 billion years ago in
      an anaerobic, high CO(2) atmosphere. The combined effect of low CO(2) and high
      O(2) levels in the modern atmosphere, and the inability of Rubisco to distinguish
      completely between CO(2) and O(2), leads to the occurrence of an oxygenation
      reaction that reduces the efficiency of photosynthesis. Among land plants, C(4)
      photosynthesis largely solves this problem by facilitating a high CO(2)/O(2)
      ratio at the site of Rubisco that resembles the atmosphere in which the ancestral
      enzyme evolved. The prediction that such conditions favor Rubiscos with higher
      kcat(CO2) and lower CO(2)/O(2) specificity (S(C/O)) is well supported, but the
      structural basis for the differences between C(3) and C(4) Rubiscos is not clear.
      Flaveria (Asteraceae) includes C(3), C(3)-C(4) intermediate, and C(4) species
      with kinetically distinct Rubiscos, providing a powerful system in which to study
      the biochemical transition of Rubisco during the evolution from C(3) to C(4)
      photosynthesis. We analyzed the molecular evolution of chloroplast rbcL and
      nuclear rbcS genes encoding the large subunit (LSu) and small subunit (SSu) of
      Rubisco from 15 Flaveria species. We demonstrate positive selection on both
      subunits, although selection is much stronger on the LSu. In Flaveria, two
      positively selected LSu amino acid substitutions, M309I and D149A, distinguish
      C(4) Rubiscos from the ancestral C(3) species and statistically account for much
      of the kinetic difference between the two groups. However, although Flaveria
      lacks a characteristic "C(4)" SSu, our data suggest that specific residue
      substitutions in the SSu are correlated with the kinetic properties of Rubisco in
      this genus.

PMID- 21172832
TI  - Selective constraints in conserved folded RNAs of drosophilid and hominid
      genomes.
AB  - Small noncoding RNAs as well as folded RNA structures in genic regions are
      crucial for many cellular processes. They are involved in posttranscriptional
      gene regulation (microRNAs), RNA modification (small nucleolar RNAs), regulation
      of splicing, correct localization of proteins, and many other processes. In most
      cases, a distinct secondary structure of the molecule is necessary for its
      correct function. Hence, selection should act to retain the structure of the
      molecule, although the underlying sequence is allowed to vary. Here, we present
      the first genome-wide estimates of selective constraints in folded RNA molecules
      in the nuclear genomes of drosophilids and hominids. In comparison to putatively
      neutrally evolving sites, we observe substantially reduced rates of substitutions
      at paired and unpaired sites of folded molecules. We estimated evolutionary
      constraints to be in the ranges of (0.974,0.991) and (0.895,1.000) for paired
      nucleotides in drosophilids and hominids, respectively. These values are
      significantly higher than for constraints at nonsynonymous sites of protein
      coding genes in both genera. Nonetheless, valleys of only moderately reduced
      fitness (s ~ 10(-4)) are sufficient to generate the observed fraction of
      nucleotide changes that are removed by purifying selection. In addition, a
      comparison of selective coefficients between drosophilids and hominids revealed
      significantly higher constraints in drosophilids, which can be attributed to the
      difference in long-term effective population size between these two groups of
      species. This difference is particularly apparent at the independently evolving
      (unpaired) sites.

PMID- 21172831
TI  - Novel protein genes in animal mtDNA: a new sex determination system in freshwater
      mussels (Bivalvia: Unionoida)?
AB  - Mitochondrial (mt) function depends critically on optimal interactions between
      components encoded by mt and nuclear DNAs. mitochondrial DNA (mtDNA) inheritance
      (SMI) is thought to have evolved in animal species to maintain mito-nuclear
      complementarity by preventing the spread of selfish mt elements thus typically
      rendering mtDNA heteroplasmy evolutionarily ephemeral. Here, we show that mtDNA
      intraorganismal heteroplasmy can have deterministic underpinnings and persist for
      hundreds of millions of years. We demonstrate that the only exception to SMI in
      the animal kingdom, that is, the doubly uniparental mtDNA inheritance system in
      bivalves, with its three-way interactions among egg mt-, sperm mt- and nucleus
      encoded gene products, is tightly associated with the maintenance of separate
      male and female sexes (dioecy) in freshwater mussels. Specifically, this mother
      through-daughter and father-through-son mtDNA inheritance system, containing
      highly differentiated mt genomes, is found in all dioecious freshwater mussel
      species. Conversely, all hermaphroditic species lack the paternally transmitted
      mtDNA (=possess SMI) and have heterogeneous macromutations in the recently
      discovered, novel protein-coding gene (F-orf) in their maternally transmitted mt
      genomes. Using immunoelectron microscopy, we have localized the F-open reading
      frame (ORF) protein, likely involved in specifying separate sexes, in
      mitochondria and in the nucleus. Our results support the hypothesis that proteins
      coded by the highly divergent maternally and paternally transmitted mt genomes
      could be directly involved in sex determination in freshwater mussels.
      Concomitantly, our study demonstrates novel features for animal mt genomes: the
      existence of additional, lineage-specific, mtDNA-encoded proteins with functional
      significance and the involvement of mtDNA-encoded proteins in extra-mt functions.
      Our results open new avenues for the identification, characterization, and
      functional analyses of ORFs in the intergenic regions, previously defined as
      "noncoding," found in a large proportion of animal mt genomes.

PMID- 21172833
TI  - Evolution of gene expression in fire ants: the effects of developmental stage,
      caste, and species.
AB  - Ants provide remarkable examples of equivalent genotypes developing into
      divergent and discrete phenotypes. Diploid eggs can develop either into queens,
      which specialize in reproduction, or workers, which participate in cooperative
      tasks such as building the nest, collecting food, and rearing the young. In
      contrast, the differentiation between males and females generally depends upon
      whether eggs are fertilized, with fertilized (diploid) eggs giving rise to
      females and unfertilized (haploid) eggs giving rise to males. To obtain a
      comprehensive picture of the relative contributions of gender (sex), caste,
      developmental stage, and species divergence to gene expression evolution, we
      investigated gene expression patterns in pupal and adult queens, workers, and
      males of two species of fire ants, Solenopsis invicta and S. richteri. Microarray
      hybridizations revealed that variation in gene expression profiles is influenced
      more by developmental stage than by caste membership, sex, or species identity.
      The second major contributor to variation in gene expression was the combination
      of sex and caste. Although workers and queens share equivalent diploid nuclear
      genomes, they have highly distinctive patterns of gene expression in both the
      pupal and the adult stages, as might be expected given their extraordinary level
      of phenotypic differentiation. Overall, the difference in the proportion of
      differentially expressed genes was greater between workers and males than between
      workers and queens or queens and males, consistent with the fact that workers and
      males share neither gender nor reproductive capability. Moreover, between-species
      comparisons revealed that the greatest difference in gene expression patterns
      occurred in adult workers, a finding consistent with the fact that adult workers
      most directly experience the distinct external environments characterizing the
      different habitats occupied by the two species. Thus, much of the evolution of
      gene expression in ants may occur in the worker caste, despite the fact that
      these individuals are largely or completely sterile. Analyses of gene expression
      evolution revealed a combination of positive selection and relaxation of
      stabilizing selection as important factors driving the evolution of such genes.

PMID- 21172835
TI  - Harvesting evolutionary signals in a forest of prokaryotic gene trees.
AB  - Phylogenomic studies produce increasingly large phylogenetic forests of trees
      with patchy taxonomical sampling. Typically, prokaryotic data generate thousands
      of gene trees of all sizes that are difficult, if not impossible, to root. Their
      topologies do not match the genealogy of lineages, as they are influenced not
      only by duplication, losses, and vertical descent but also by lateral gene
      transfer (LGT) and recombination. Because this complexity in part reflects the
      diversity of evolutionary processes, the study of phylogenetic forests is thus a
      great opportunity to improve our understanding of prokaryotic evolution. Here, we
      show how the rich evolutionary content of such novel phylogenetic objects can be
      exploited through the development of new approaches designed specifically for
      extracting the multiple evolutionary signals present in the forest of life, that
      is, by slicing up trees into remarkable bits and pieces: clans, slices, and
      clips. We harvested a forest of 6,901 unrooted gene trees comprising up to 100
      prokaryotic genomes (41 archaea and 59 bacteria) to search for evolutionary
      events that a species tree would not account for. We identified 1) trees and
      partitions of trees that reflected the lifestyle of organisms rather than their
      taxonomy, 2) candidate lifestyle-specific genetic modules, used by distinct
      unrelated organisms to adapt to the same environment, 3) gene families,
      nonrandomly distributed in the functional space, that were frequently exchanged
      between archaea and bacteria, sometimes without major changes in their sequences.
      Finally, 4) we reconstructed polarized networks of genetic partnerships between
      archaea and bacteria to describe some of the rules affecting LGT between these
      two Domains.

PMID- 21172834
TI  - Reverse evolution in RH1 for adaptation of cichlids to water depth in Lake
      Tanganyika.
AB  - Reverse evolution is a widespread phenomenon in biology, but the genetic
      mechanism for the reversal of a genetic change for adaptation to the ancestral
      state is not known. Here, we report the first case of complete reverse evolution
      of two amino acids, serine and alanine, at a single position in RH1 opsin pigment
      for adaptation to water depth. We determined RH1 sequences of cichlid fishes from
      four tribes of Lake Tanganyika with different habitat depths. Most of the species
      were divided into two types: RH1 with 292A for species in shallow water or 292S
      for species in deep water. Both types were adapted to their ambient light
      environments as indicated by the absorption spectra of the RH1 pigments. Based on
      the RH1 locus tree and ecological data, we inferred the ancestral amino acids at
      position 292 and the distribution of the depth ranges (shallow or deep) of
      ancestral species of each tribe. According to these estimates, we identified two
      distinct parallel adaptive evolutions: The replacement A292S occurred at least
      four times for adaptation from shallow to deep water, and the opposite
      replacement S292A occurred three times for adaptation from deep to shallow water.
      The latter parallelism represents the complete reverse evolution from the derived
      to the ancestral state, following back adaptive mutation with reversal of the RH1
      pigment function accompanied by reversal of the species habitat shift.

PMID- 21172836
TI  - Second brain death examination may negatively affect organ donation.
AB  - BACKGROUND: Little is known about the impact of the requirement for a second
      brain death examination on organ donation. In New York State, 2 examinations 6
      hours apart have been recommended by a Department of Health panel. METHODS: We
      reviewed data for 1,229 adult and 82 pediatric patients pronounced brain dead in
      100 New York hospitals serviced by the New York Organ Donor Network from June 1,
      2007, to December 31, 2009. We reviewed the time interval between the 2 clinical
      brain death examinations and correlated this brain death declaration interval to
      day of the week, hospital size, and organ donation. RESULTS: None of the patients
      declared brain dead were found to regain brainstem function upon repeat
      examination. The mean brain death declaration interval between the 2 examinations
      was 19.2 hours. A 26% reduction in brain death examination frequency was seen on
      weekends when compared to weekdays (p = 0.0018). The mean brain death interval
      was 19.9 hours for 0-750 bed hospitals compared to 16.0 hours for hospitals with
      more than 750 beds (p = 0.0015). Consent for organ donation decreased from 57% to
      45% as the brain death declaration interval increased. Conversely, refusal of
      organ donation increased from 23% to 36% as the brain death interval increased. A
      total of 166 patients (12%) sustained a cardiac arrest between the 2 examinations
      or after the second examination. CONCLUSION: A single brain death examination to
      determine brain death for patients older than 1 year should suffice. In practice,
      observation time to a second neurologic examination was 3 times longer than the
      proposed guideline and associated with substantial intensive care unit costs and
      loss of viable organs.

PMID- 21172837
TI  - The case for simplifying brain death criteria.

PMID- 21172838
TI  - International issues: on the localization of saintly neurology: a neurology
      elective in India.

PMID- 21172839
TI  - Teaching Video NeuroImages: complex partial seizure evolving into a psychogenic
      nonepileptic seizure.

PMID- 21172840
TI  - FDG-PET improves surgical outcome in negative MRI Taylor-type focal cortical
      dysplasias.
AB  - OBJECTIVE: To determine the diagnostic accuracy and prognostic value of 18FDG-PET
      in a recent series of patients operated for intractable partial epilepsy
      associated with histologically proven Taylor-type focal cortical dysplasia
      (TTFCD) and negative MRI. METHODS: Of 23 consecutive patients (12 male, 7-38
      years old) with negative 1.5-Tesla MRI, 10 exhibited subtle nonspecific
      abnormalities (e.g., unusual sulcus depth or gyral pattern) and the 13 others had
      strictly normal MRI. FDG-PET was analyzed both visually after coregistration on
      MRI and using SPM5 software. Metabolic data were compared with the epileptogenic
      zone (EZ) determined by stereo-EEG (SEEG) and surgical outcome. RESULTS: Visual
      PET analysis disclosed a focal or regional hypometabolism in 18 cases (78%)
      corresponding to a single gyrus (n = 9) or a larger cortical region (n = 9).
      PET/MRI coregistration detected a partially hypometabolic gyrus in 4 additional
      cases. SPM5 PET analysis (n = 18) was concordant with visual analysis in 13
      cases. Location of PET abnormalities was extratemporal in all cases, involving
      eloquent cortex in 15 (65%). Correlations between SEEG, PET/MRI, and histologic
      findings (n = 20) demonstrated that single hypometabolic gyri (n = 11)
      corresponded to EZ and TTFCD, which was localized at the bottom of the sulcus.
      Larger hypometabolic areas (n = 9) also included the EZ and the dysplastic cortex
      but were more extensive. Following limited cortical resection (mean follow-up 4
      years), seizure freedom without permanent motor deficit was obtained in 20/23
      patients (87%). CONCLUSIONS: 18FDG-PET coregistered with MRI is highly sensitive
      to detect TTFCD and greatly improves diagnosis and surgical prognosis of patients
      with negative MRI.

PMID- 21172841
TI  - Genetic predisposition of white matter infarction with protein S deficiency and
      R355C mutation.
AB  - BACKGROUND: The association between protein S deficiency (PSD) and ischemic
      stroke is controversial and warrants further investigation. METHODS: We conducted
      a genotype and MRI correlation study in a Chinese family in which hereditary PSD
      cosegregated with premature ischemic strokes. Six out of 11 family members
      inherited PSD type III in an autosomal dominant manner. RESULTS: Among all PSD
      members, a novel missense mutation 1063C->T in exon 10 of protein S alpha (PROS1)
      was identified, which encoded a substitution of arginine to cysteine at position
      355 (R355C) in the first globular domain of laminin A of protein S. Wild-type
      PROS1 sequences were retained in non-PSD members. MRI detected deep white matter
      infarctions predominantly distributed in the borderzone regions. The infarct
      topography was homogeneous in all adult mutant carriers. By contrast, cerebral
      infarction was absent in nonmutant carriers. Extensive investigation in the
      family did not reveal any confounding stroke risk. Haplotype analysis with high
      density single nucleotide polymorphism markers revealed a 6.1-Mb minimally
      rearranged region (rs12494685 to rs1598240) in 3q11.2, lod = 3.0. Among the 7
      annotated genes in this region, PROS1 is known to be associated with thrombotic
      disorders. MRI screening in an additional 10 PSD families without R355C showed no
      cerebral infarction. CONCLUSIONS: PROS1 R355C mutation cosegregated with PSD type
      III and premature white matter infarctions in the index family. The findings
      substantiate an association between PSD and stroke. Study of the mechanism
      underlying this association may improve our understanding of premature
      cryptogenic white matter infarction.

PMID- 21172842
TI  - Randomized, double-blind, placebo-controlled trial of hydroxyurea in spinal
      muscular atrophy.
AB  - OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of
      hydroxyurea (HU) in spinal muscular atrophy (SMA) in a randomized, double-blind,
      placebo-controlled trial. METHODS: Twenty-eight patients with type 2 SMA and 29
      patients with type 3 SMA were randomly assigned (2:1) to receive HU or matching
      placebo for 18 months. HU was initiated at 10 mg/kg/day with an 8-week titration
      to 20 mg/kg/day. Subjects were assessed at baseline (T0) and monthly for the
      first 2 months (T1-T2) and then every 2 months throughout treatment (T3-T10) and
      posttreatment periods (T11-T13). The primary outcome measures were the Gross
      Motor Function Measure (GMFM), Manual Muscle Test (MMT), and serum full-length
      survivor motor neuron (flSMN) mRNA. The secondary outcome measures were Modified
      Hammersmith Functional Motor Scale and forced vital capacity (FVC). RESULTS:
      Fifty-five patients completed this trial, which lasted from March 2007 to June
      2009. Except for neutropenia, we found no differences in adverse events between
      the 2 groups. Compared with the placebo group, the HU group had -1.88 for GMFM (p
      = 0.11), -0.55 for MMT (p = 0.49), and 2.17 for flSMN mRNA (p = 0.13). Similarly,
      we found no difference in mean improvement of the secondary endpoints. Both
      groups had a trend toward a decline in FVC with little change in strength and
      motor function. CONCLUSION: Under the current regimen and schedule, HU brought
      about no improvement in patients with type 2 and 3 SMA, and its main side effect
      was neutropenia. CLASSIFICATION OF EVIDENCE: This trial provides Class I evidence
      that HU 20 mg/kg/day does not effectively treat SMA.

PMID- 21172843
TI  - TDP-43 subtypes are associated with distinct atrophy patterns in frontotemporal
      dementia.
AB  - BACKGROUND: We sought to describe the antemortem clinical and neuroimaging
      features among patients with frontotemporal lobar degeneration with TDP-43
      immunoreactive inclusions (FTLD-TDP). METHODS: Subjects were recruited from a
      consecutive series of patients with a primary neuropathologic diagnosis of FTLD
      TDP and antemortem MRI. Twenty-eight patients met entry criteria: 9 with type 1,
      5 with type 2, and 10 with type 3 FTLD-TDP. Four patients had too sparse FTLD-TDP
      pathology to be subtyped. Clinical, neuropsychological, and neuroimaging features
      of these cases were reviewed. Voxel-based morphometry was used to assess regional
      gray matter atrophy in relation to a group of 50 cognitively normal control
      subjects. RESULTS: Clinical diagnosis varied between the groups: semantic
      dementia was only associated with type 1 pathology, whereas progressive nonfluent
      aphasia and corticobasal syndrome were only associated with type 3. Behavioral
      variant frontotemporal dementia and frontotemporal dementia with motor neuron
      disease were seen in type 2 or type 3 pathology. The neuroimaging analysis
      revealed distinct patterns of atrophy between the pathologic subtypes: type 1 was
      associated with asymmetric anterior temporal lobe atrophy (either left- or right
      predominant) with involvement also of the orbitofrontal lobes and insulae; type 2
      with relatively symmetric atrophy of the medial temporal, medial prefrontal, and
      orbitofrontal-insular cortices; and type 3 with asymmetric atrophy (either left-
      or right-predominant) involving more dorsal areas including frontal, temporal,
      and inferior parietal cortices as well as striatum and thalamus. No significant
      atrophy was seen among patients with too sparse pathology to be subtyped.
      CONCLUSIONS: FTLD-TDP subtypes have distinct clinical and neuroimaging features,
      highlighting the relevance of FTLD-TDP subtyping to clinicopathologic
      correlation.

PMID- 21172844
TI  - Does TDP-43 type confer a distinct pattern of atrophy in frontotemporal lobar
      degeneration?
AB  - OBJECTIVE: To determine whether TDP-43 type is associated with distinct patterns
      of brain atrophy on MRI in subjects with pathologically confirmed frontotemporal
      lobar degeneration (FTLD). METHODS: In this case-control study, we identified all
      subjects with a pathologic diagnosis of FTLD with TDP-43 immunoreactive
      inclusions (FTLD-TDP) and at least one volumetric head MRI scan (n = 42). In each
      case we applied published criteria for subclassification of FTLD-TDP into FTLD
      TDP types 1-3. Voxel-based morphometry was used to compare subjects with each of
      the different FTLD-TDP types to age- and gender-matched normal controls (n = 30).
      We also assessed different pathologic and genetic variants within, and across,
      the different types. RESULTS: Twenty-two subjects were classified as FTLD-TDP
      type 1, 9 as type 2, and 11 as type 3. We identified different patterns of
      atrophy across the types with type 1 showing frontotemporal and parietal atrophy,
      type 2 predominantly anterior temporal lobe atrophy, and type 3 predominantly
      posterior frontal atrophy. Within the FTLD-TDP type 1 group, those with a
      progranulin mutation had significantly more lateral temporal lobe atrophy than
      those without. All type 2 subjects were diagnosed with semantic dementia.
      Subjects with a pathologic diagnosis of FTLD with motor neuron degeneration had a
      similar pattern of atrophy, regardless of whether they were type 1 or type 3.
      CONCLUSIONS: Although there are different patterns of atrophy across the
      different FTLD-TDP types, it appears that genetic and pathologic factors may also
      affect the patterns of atrophy.

PMID- 21172845
TI  - Cerebral microbleeds, retinopathy, and dementia: the AGES-Reykjavik Study.
AB  - OBJECTIVE: To determine whether microvascular damage, indicated by cerebral
      microbleeds (CMBs) and retinal microvascular signs, is associated with cognitive
      function and dementia in older persons. METHODS: This is a cross-sectional study
      of 3,906 participants (mean age 76 years; 58% women) in the AGES-Reykjavik Study
      (2002-2006). We assessed CMBs on MRI and retinal microvascular signs on digital
      retinal images. Composite Z scores of memory, processing speed, and executive
      function were derived from a battery of neurocognitive tests. Dementia and
      subtypes were diagnosed following international criteria. Regression models were
      used to relate cognitive Z scores and dementia to CMBs and retinal microvascular
      signs, adjusting for demographics, cardiovascular factors, and brain ischemic
      lesions. RESULTS: People with multiple (>= 2) CMBs had lower Z scores on tests of
      processing speed (beta-coefficient -0.16; 95% confidence interval -0.26 to -0.05)
      and executive function (-0.14; -0.24 to -0.04); results were strongest for having
      multiple CMBs located in the deep hemispheric or infratentorial areas. The odds
      ratio of vascular dementia was 2.32 (95% confidence interval 1.02 to 5.25) for
      multiple CMBs and 1.95 (1.04 to 3.62) for retinopathy. Having both CMBs and
      retinopathy, compared to having neither, was significantly associated with
      markedly slower processing speed (-0.25; -0.37 to -0.12), poorer executive
      function (-0.19; -0.31 to -0.07), and an increased odds ratio of vascular
      dementia (3.10; 1.11 to 8.62). CONCLUSION: Having multiple CMBs or concomitant
      CMBs and retinopathy is associated with a profile of vascular cognitive
      impairment. These findings suggest that microvascular damage, as indicated by
      CMBs and retinopathy lesions, has functional consequences in older men and women
      living in the community.

PMID- 21172846
TI  - Complementary therapy use in patients with glioma: an observational study.
AB  - OBJECTIVE: Despite novel multimodal therapeutic approaches, the vast majority of
      glial tumors are not curable. Patients may search for complementary therapies in
      order to contribute to the fight against their disease or to relieve symptoms
      induced by their brain tumor. The extent of the use of complementary or
      alternative therapies, the patients' rationale behind it, and the cost of
      complementary therapy for gliomas are not known. We used a questionnaire and the
      database of the German Glioma Network to evaluate these questions. METHODS: A
      total of 621 questionnaires were available for evaluation from patients with
      glial tumors of WHO grades II to grade IV. The patients were recruited from 6
      neuro-oncologic centers in Germany. Complementary therapy was defined as methods
      or compounds not used in routine clinical practice and not scientifically
      evaluated. RESULTS: Forty percent of the responding patients reported the use of
      complementary therapies. Significant differences between the group of
      complementary therapy users and nonusers were seen with respect to age (younger >
      older), gender (female > male), and education (high education level > low
      education level). The motivation for complementary therapy use was not driven by
      unsatisfactory clinical care by the neuro-oncologists, but by the wish to add
      something beneficial to the standard of care. CONCLUSIONS: In clinical practice,
      patients' use of complementary therapies may be largely overseen and
      underestimated. The major motivation is not distrust in conventional therapies.
      Neuro-oncologists should be aware of this phenomenon and encourage an open but
      critical dialogue with their patients.

PMID- 21172847
TI  - A diagnostic and therapeutic scheme for a solitary cysticercus granuloma.
AB  - BACKGROUND: Solitary cysticercus granuloma (SCG) is one of the most common forms
      of presentation of neurocysticercosis (NCC). The diagnostic workup and management
      approach to this condition remain uncertain and controversial. OBJECTIVE: To
      review evidence and develop a consensus approach to the diagnosis and treatment
      of SCG. METHODS: A multidisciplinary expert group meeting was convened in order
      to review and discuss various aspects of management of patients with SCG.
      Evidence reviewed was classified and a consensus was evolved according to
      standard protocols. RESULTS: SCG is commonly recognized on CT as an enhancing
      lesion measuring <20 mm. Further evaluation with MRI does not add much
      information. The use of antihelminthic agents (specifically, albendazole in
      combination with corticosteroids) and corticosteroids alone have been shown to
      improve radiologic resolution and seizure outcome in patients with SCG. However,
      the sizes of the effects are modest. By convention, all patients with SCG
      presenting with seizures are initiated on antiepileptic drugs (AEDs). Available
      evidence suggests that withdrawal of AEDs after complete resolution of the SCG is
      safe. There is a high risk of seizure relapse after AED withdrawal in patients
      with calcific residue following resolution of the SCG. The duration of AED
      prophylaxis in these individuals is unclear. CONCLUSIONS: It is desirable to have
      large, multicenter trials with sufficiently long follow-up, comparing outcomes
      with the use of antihelminthics with or without corticosteroids and
      corticosteroids alone in order to dissect out the benefits accrued due to each of
      these classes of drugs.

PMID- 21172848
TI  - Acute encephalomyelitis syndromes associated with H1N1 09 influenza vaccination.

PMID- 21172849
TI  - An independent replication of PARK16 in Asian samples.

PMID- 21172850
TI  - Premature intracranial arterial calcification in a patient with
      hyperhomocysteinemia.

PMID- 21172851
TI  - Neuromyelitis optica preceded by hyperCKemia episode.

PMID- 21172852
TI  - Teaching Neuroimages: adrenoleukodystrophy presenting as raised intracranial
      pressure.

PMID- 21172853
TI  - Smokers who are also using smokeless tobacco products in the US: a national
      assessment of characteristics, behaviours and beliefs of 'dual users'.
AB  - BACKGROUND: Marketing and advertising of smokeless tobacco products towards
      cigarette smokers has increased recently. Because the use of multiple tobacco
      products is a growing public health concern, the present work assesses the use of
      smokeless tobacco among cigarette smokers, a behaviour termed as 'dual use', as
      well as attitudes and beliefs on their 'dual use' of tobacco. METHODS: Data were
      used from the 2008 Consumer Styles survey, a nationally representative, mail-in
      survey of consumers in the USA (n=10,108). RESULTS: 'Dual use' was more common
      among cigarette smokers who were young, white men living in the Midwest or South.
      The majority of 'dual users' reported using smokeless tobacco in places where
      they could not smoke (67.7%) and did not believe smokeless tobacco would help in
      quitting smoking (75.1%). 'Dual users' reported planning to quit within the next
      6 months less often than adults who smoke cigarettes exclusively and close to
      half (42.3%) never plan to quit smoking. CONCLUSIONS: Tobacco use is attributed
      to a number of diseases and deaths worldwide, and cessation of tobacco use can
      reduce these health risks. The prevalent use of smokeless tobacco in places with
      smoking restrictions and lack of planning to quit by 'dual users' suggest the
      need to promote cessation among these users.

PMID- 21172854
TI  - Pig's blood in cigarette filters: how a single news release highlighted tobacco
      industry concealment of cigarette ingredients.
AB  - The tobacco industry is not obligated to disclose ingredients and additives used
      in manufactured tobacco production. This paper describes global reaction to a
      press release highlighting evidence that porcine haemoglobin ("pig's blood") was
      sometimes used in cigarette manufacturing while never being disclosed to smokers.
      The case study illustrates the power of press releases to ignite major interest
      in tobacco control issues.

PMID- 21172855
TI  - Thirdhand smoke: here to stay.

PMID- 21172856
TI  - Long term outcome of thermal anterior capsulotomy for chronic, treatment
      refractory depression.
AB  - BACKGROUND: There is very limited evidence for the efficacy of any specific
      therapeutic intervention in chronic, treatment refractory major depression.
      Thermal anterior capsulotomy (ACAPS) is a rarely performed but established
      therapeutic procedure for this patient group. While benefit has been claimed,
      previous ACAPS reports have provided limited information. Detailed prospective
      reporting of therapeutic effects and side effects is required. OBJECTIVE: To
      report a prospective study of therapeutic effect, mental status, quality of life,
      social functioning and neurocognitive functioning in individuals with chronic
      treatment refractory major depression, treated with ACAPS. METHOD: A prospective
      case series of 20 patients treated with ACAPS between 1992 and 1999 were
      reassessed at a mean follow-up of 7.0+/-3.4 years. Data were collected
      preoperatively and at long term follow-up. Structural MRI was performed in 14
      participants. RESULTS: According to a priori criteria, at long term follow-up,
      50% were classified as 'responders' and 40% as 'remitters'. Fifty-five per cent
      were classified as 'improved'; 35% were 'unchanged'; and 10% had 'deteriorated'.
      Neurocognitive and personality testing were not significantly different at follow
      up. A trend towards improvement in some aspects of executive neuropsychological
      functioning was observed. Significant adverse effects were infrequent and there
      were no deaths. CONCLUSIONS: ACAPS may represent an effective intervention for
      some patients with chronic, disabling, treatment refractory major depression that
      has failed to respond to other therapeutic approaches. The adverse effect burden
      within this population was modest, with no evidence of generalised impairment of
      neurocognitive functioning.

PMID- 21172857
TI  - Diagnosing variant Creutzfeldt-Jakob disease: a retrospective analysis of the
      first 150 cases in the UK.
AB  - INTRODUCTION: Establishing an early clinical diagnosis in variant Creutzfeldt
      Jakob disease (vCJD) can be difficult, resulting in extended periods of
      uncertainty for many families and sometimes a view that patients have been
      subjected to unnecessary investigations. This issue is accentuated by the
      progressive nature of vCJD and by the difficulty in achieving a confident
      clinical diagnosis before an advanced stage of illness. Although diagnostic delay
      may be a result of the non-specific early clinical features, a systematic
      analysis of the process of diagnosis was undertaken, with the aim of trying to
      achieve earlier diagnosis of vCJD. METHODS: Retrospective case file analysis was
      undertaken of the first 150 definite and clinically probable cases of vCJD
      identified by the UK surveillance system. RESULTS: There is a significant
      interval between illness onset and presentation to a primary care physician,
      which is influenced by the nature of the initial clinical features. Neurological
      review is invariably sought following the development of clinical signs and a
      diagnosis is then established relatively quickly. Despite the progressive
      clinical course, a confident clinical diagnosis is not usually achieved until a
      relatively advanced stage of illness (mean time to diagnosis 10.5 months) with a
      more rapid clinical progression accounting for those cases diagnosed earlier
      after symptom onset. CONCLUSIONS: Early clinical diagnosis in vCJD is not
      possible in the great majority of cases because of non-specific initial symptoms.
      Once neurological signs develop, a diagnosis is usually made promptly but this is
      often at a relatively advanced stage of illness. The inherent delays in the
      diagnosis of vCJD have implications for those involved in both public health and
      therapeutics.

PMID- 21172859
TI  - Thrombolysis for ischaemic stroke: impact of the extension of the time-window in
      daily practice.

PMID- 21172860
TI  - Neurological picture. Isolated hypoglossal nerve palsy caused by synovial cyst.

PMID- 21172858
TI  - Interpersonal traits change as a function of disease type and severity in
      degenerative brain diseases.
AB  - BACKGROUND: Different degenerative brain diseases result in distinct personality
      changes as a result of divergent patterns of brain damage; however, little is
      known about the natural history of these personality changes throughout the
      course of each disease. OBJECTIVE: To investigate how interpersonal traits change
      as a function of degenerative brain disease type and severity. METHODS: Using the
      Interpersonal Adjective Scales, informant ratings of retrospective premorbid and
      current scores for dominance, extraversion, warmth and ingenuousness were
      collected annually for 1 to 4&emsp14;years on 188 patients (67 behavioural
      variant frontotemporal dementia (bvFTD), 40 semantic dementia (SemD), 81
      Alzheimer's disease (AD)) and 65 older healthy controls. Using random coefficient
      models, interpersonal behaviour scores at very mild, mild or moderate-to-severe
      disease stages were compared within and between patient groups. RESULTS: Group
      level changes from premorbid personality occurred as a function of disease type
      and severity, and were apparent even at a very mild disease stage (Clinical
      Dementia Rating=0.5) for all three diseases. Decreases in interpersonal traits
      were associated with emotional affiliation (ie, extraversion, warmth and
      ingenuousness) and more rigid interpersonal behaviour differentiated bvFTD and
      SemD patients from AD patients. CONCLUSIONS: Specific changes in affiliative
      interpersonal traits differentiate degenerative brain diseases even at a very
      mild disease stage, and patterns of personality change differ across bvFTD, SemD
      and AD with advancing disease. This study describes the typical progression of
      change of interpersonal traits in each disease, improving the ability of
      clinicians and caregivers to predict and plan for symptom progression.

PMID- 21172861
TI  - B-cell-activating factor in rituximab-treated patients with anti-MAG
      polyneuropathy.
AB  - BACKGROUND: Antimyelin-associated glycoprotein (MAG) polyneuropathy is a slowly
      progressive distal form of mixed motor-sensory polyneuropathy that is scarcely
      responsive to conventional immunosuppressive therapy. Rituximab, a B-cell
      depleting antibody, is a promising therapeutic choice for anti-MAG
      polyneuropathy, and the evaluation of factors, such as B-cell-activating factor
      (BAFF), that control B-cell homeostasis is important to understand how this drug
      works. METHODS: Using an ELISA method, the authors measured serum BAFF
      concentrations in 23 patients with anti-MAG polyneuropathy, before and after
      rituximab therapy, in 20 neurological controls and in 14 healthy subjects. The
      patients were followed up over a mean period of 38+/-12 months and categorised as
      responders/non-responders, and, between the responders, as relapsing/non
      relapsing. RESULTS: Pretherapy serum BAFF concentrations in non-responders were
      higher than in responders (cut-off 1665 pg/ml; sensitivity 71.4%; specificity
      93.7%; likelihood ratio 11.4), with the highest post-therapy increases in
      responders. In the responders who relapsed, relapses occurred when serum BAFF
      concentrations returned to baseline values, 1-2 years after blood B-cell
      reappearance. CONCLUSIONS: Before and during therapy, measurements of serum BAFF
      in rituximab-treated patients with anti-MAG polyneuropathy may help predict the
      response to the therapy. The findings in this study also provide information
      about rituximab-induced modifications on B-cell homeostatic regulation.

PMID- 21172862
TI  - Peripheral neuropathies in Sjogren syndrome: a new reappraisal.
AB  - BACKGROUND: The prevalence of peripheral neuropathy in patients with Sjogren
      syndrome remains unclear owing to conflicting results in the published series,
      with numbers ranging from 2% to over 60% of Sjogren syndrome patients. Whether
      peripheral neuropathy is a feature of the systemic or glandular disease or
      whether it is related to a circulating antineuronal antibody remains also
      uncertain. METHODS: The authors reviewed the records of patients with primary
      Sjogren syndrome (pSS), fulfilling the Revised European-American Classification
      Criteria, seen in their department from 1992 to 2009. The patients with
      previously recorded neuropathic features were re-examined clinically and
      electrophysiologically. Other causes of polyneuropathy were excluded. The authors
      also searched for circulating antineural antibodies using immunofluorescence and
      western blot and for antibodies against muscarinic and nicotinic acetylcholine
      receptors as potential biomarkers. RESULTS: 509 cases met the diagnostic criteria
      for pSS. Among these, 44 patients were recorded as having neuropathic symptoms.
      After completing the evaluation, however, only nine (1.8%) had polyneuropathy
      with objective clinical signs and abnormal electrophysiological findings. The
      neuropathy was axonal in all, in five pure sensory and in four sensorimotor. The
      patients with peripheral neuropathy had extraglandular manifestations such as
      palpable purpura and vasculitis. No evidence of antineural autoimmunity was
      found, and no candidate biomarkers were identified. CONCLUSION: Polyneuropathy is
      a rare manifestation of pSS occurring in 1.8% of patients. In the majority of
      patients, it is a late event and frequently associated with systemic disease or
      risk factors for lymphoma development.

PMID- 21172863
TI  - Structural neuroanatomy of face processing in frontotemporal lobar degeneration.
AB  - Impairments of face processing occur frequently in frontotemporal lobar
      degeneration (FTLD) but the neuroanatomical basis for these deficits has seldom
      been studied systematically. Here a prospective voxel based morphometry study is
      described addressing the neuroanatomy of two key dimensions of face processing-
      face identification and facial emotion recognition--in a single cohort of 32
      patients with FTLD (19 with frontal variant and 13 with temporal variant FTLD).
      For the FTLD group as a whole, face identification was positively associated with
      grey matter in the right anterior fusiform gyrus while recognition of angry
      expressions was positively associated with grey matter in the bilateral insula
      cortex. FTLD provides a perspective on the neuroanatomy of face processing that
      is complementary to focal lesion and normal functional imaging work.

PMID- 21172864
TI  - Intraoperative observation of changes in cochlear nerve action potentials during
      exposure to electromagnetic fields generated by mobile phones.
AB  - BACKGROUND: The rapid spread of devices generating electromagnetic fields (EMF)
      has raised concerns as to the possible effects of this technology on humans. The
      auditory system is the neural organ most frequently and directly exposed to
      electromagnetic activity owing to the daily use of mobile phones. In recent
      publications, a possible correlation between mobile phone usage and central
      nervous system tumours has been detected. Very recently a deterioration in
      otoacoustic emissions and in the auditory middle latency responses after
      intensive and long-term magnetic field exposure in humans has been demonstrated.
      METHODS: To determine with objective observations if exposure to mobile phone EMF
      affects acoustically evoked cochlear nerve compound action potentials, seven
      patients suffering from Meniere's disease and undergoing retrosigmoid vestibular
      neurectomy were exposed to the effects of mobile phone placed over the craniotomy
      for 5 min. RESULTS: All patients showed a substantial decrease in amplitude and a
      significant increase in latency of cochlear nerve compound action potentials
      during the 5 min of exposure to EMF. These changes lasted for a period of around
      5 min after exposure. DISCUSSION: The possibility that EMF can produce relatively
      long-lasting effects on cochlear nerve conduction is discussed and analysed in
      light of contrasting previous literature obtained under non-surgical conditions.
      Limitations of this novel approach, including the effects of the anaesthetics,
      craniotomy and surgical procedure, are presented in detail.

PMID- 21172866
TI  - Substance P is a key mediator of stress-induced protection from allergic
      sensitization via modified antigen presentation.
AB  - Interaction between the nervous and immune systems greatly contributes to
      inflammatory disease. In organs at the interface between our body and the
      environment, the sensory neuropeptide substance P (SP) is one key mediator of an
      acute local stress response through neurogenic inflammation but may also alter
      cytokine balance and dendritic cell (DC) function. Using a combined murine
      allergic inflammation/noise stress model with C57BL/6 mice, we show in this paper
      that SP--released during repeated stress exposure--has the capacity to markedly
      attenuate inflammation. In particular, repeated stress exposure prior to allergen
      sensitization increases DC-nerve fiber contacts, enhances DC migration and
      maturation, alters cytokine balance, and increases levels of IL-2 and T
      regulatory cell numbers in local lymph nodes and inflamed tissue in a neurokinin
      1-SP-receptor (neurokinin-1 receptor)-dependent manner. Concordantly, allergic
      inflammation is significantly reduced after repeated stress exposure. We conclude
      that SP/repeated stress prior to immune activation acts protolerogenically and
      thereby beneficially in inflammation.

PMID- 21172865
TI  - Plasmacytoid dendritic cell dichotomy: identification of IFN-alpha producing
      cells as a phenotypically and functionally distinct subset.
AB  - Plasmacytoid dendritic cells (pDC) produce large amounts of type I IFN in
      response to invading pathogens, but can also suppress immune responses and
      promote tolerance. In this study, we show that in mice, these functions are
      attributable to two distinct pDC subsets, one of which gives rise to the other.
      CD9(pos)Siglec-H(low) pDC secrete IFN-alpha when stimulated with TLR agonists,
      induce CTLs, and promote protective antitumor immunity. By contrast,
      CD9(neg)Siglec-H(high) pDC secrete negligible amounts of IFN-alpha, induce
      Foxp3(+) CD4(+) T cells, and fail to promote antitumor immunity. Although newly
      formed pDC in the bone marrow are CD9(pos) and are capable of producing IFN
      alpha, after these cells traffic to peripheral tissues, they lose CD9 expression
      and the ability to produce IFN-alpha. We propose that newly generated pDC
      mobilized from the bone marrow, rather than tissue-resident pDC, are the major
      source of IFN-alpha in infected hosts.

PMID- 21172867
TI  - CD4 T cells promote rather than control tuberculosis in the absence of PD-1
      mediated inhibition.
AB  - Although CD4 T cells are required for host resistance to Mycobacterium
      tuberculosis, they may also contribute to pathology. In this study, we examine
      the role of the inhibitory receptor PD-1 and its ligand PD-L1 during M.
      tuberculosis infection. After aerosol exposure, PD-1 knockout (KO) mice develop
      high numbers of M. tuberculosis-specific CD4 T cells but display markedly
      increased susceptibility to infection. Importantly, we show that CD4 T cells
      themselves drive the increased bacterial loads and pathology seen in infected PD
      1 KO mice, and PD-1 deficiency in CD4 T cells is sufficient to trigger early
      mortality. PD-L1 KO mice also display enhanced albeit less severe susceptibility,
      indicating that T cells are regulated by multiple PD ligands during M.
      tuberculosis infection. M. tuberculosis-specific CD8 T cell responses were normal
      in PD-1 KO mice, and CD8 T cells only had a minor contribution to the exacerbated
      disease in the M. tuberculosis-infected PD-1 KO and PD-L1 KO mice. Thus, in the
      absence of the PD-1 pathway, M. tuberculosis benefits from CD4 T cell responses,
      and host resistance requires inhibition by PD-1 to prevent T cell-driven
      exacerbation of the infection.

PMID- 21172868
TI  - IL-23-mediated psoriasis-like epidermal hyperplasia is dependent on IL-17A.
AB  - IL-23 and Th17 cells producing IL-17A and IL-22 are found in excess in skin
      affected by psoriasis. Previous studies showed that IL-22, but not IL-17A,
      mediates psoriasis-like epidermal hyperplasia following recombinant murine (rm)IL
      23 injections into skin. To further investigate the role of IL-17A, ears of mice
      were injected with rmIL-23. Investigators blinded to treatment conditions and
      mouse genotypes measured ear swelling, epidermal thickness, and cytokine
      expression. In wild-type (WT) mice, rmIL-23 induced ear swelling (p < 0.001, all
      p values versus saline), epidermal hyperplasia by histology (p < 0.001) and
      confocal microscopy (p < 0.004), and expression of both IL-17A and IL-22. As
      expected, rmIL-23 injections into IL-22(-/-) mice resulted in relatively little
      ear swelling (p < 0.09) and epidermal hyperplasia (p < 0.51 by histology and p <
      0.75 by confocal microscopy). Notably, rmIL-23 injections into IL-17A(-/-) mice
      produced little ear swelling (p < 0.001, versus IL-23-injected WT mice) and
      epidermal hyperplasia (p < 0.001 by histology and p < 0.005 by confocal
      microscopy), even though IL-22 was readily induced in these mice. Furthermore,
      systemic delivery of blocking Abs directed against either IL-22 or IL-17A
      completely inhibited IL-23-induced epidermal hyperplasia in WT mice. These
      results demonstrate that IL-17A, like IL-22, is a downstream mediator for IL-23
      induced changes in murine skin and that both of these Th17 cytokines are
      necessary to produce IL-23-mediated skin pathology. IL-17A may represent an
      attractive therapeutic target in individuals with psoriasis by blocking
      downstream effects of IL-23.

PMID- 21172870
TI  - Comment on "Regulatory T cells protect from local and systemic bone destruction
      in arthritis".

PMID- 21172869
TI  - IL-17 contributes to cell-mediated defense against pulmonary Yersinia pestis
      infection.
AB  - Pneumonic plague is one of the world's most deadly infectious diseases. The
      causative bacterium, Yersinia pestis, has the potential to be exploited as a
      biological weapon, and no vaccine is available. Vaccinating B cell-deficient mice
      with D27-pLpxL, a live attenuated Y. pestis strain, induces cell-mediated
      protection against lethal pulmonary Y. pestis challenge. In this article, we
      demonstrate that prime/boost vaccination with D27-pLpxL confers better protection
      than prime-only vaccination. The improved survival does not result from enhanced
      bacterial clearance but is associated with increased levels of IL-17 mRNA and
      protein in the lungs of challenged mice. The boost also increases pulmonary
      numbers of IL-17-producing CD4 T cells. Interestingly, most of these cells
      simultaneously produce canonical type 1 and type 17 cytokines; most produce IL-17
      and TNF-alpha, and many produce IL-17, TNF-alpha, and IFN-gamma. Neutralizing IL
      17 counteracts the improved survival associated with prime/boost vaccination
      without significantly impacting bacterial burden. Thus, IL-17 appears to mediate
      the enhanced protection conferred by booster immunization. Although neutralizing
      IL-17 significantly reduces neutrophil recruitment to the lungs of mice
      challenged with Y. pestis, this impact is equally evident in mice that receive
      one or two immunizations with D27-pLpxL, suggesting it cannot suffice to account
      for the improved survival that results from booster immunization. We conclude
      that IL-17 plays a yet to be identified role in host defense that enhances
      protection against pulmonary Y. pestis challenge, and we suggest that pneumonic
      plague vaccines should aim to induce mixed type 1 and type 17 cellular responses.

PMID- 21172871
TI  - Comment on "Conventional B2 B cell depletion ameliorates whereas its adoptive
      transfer aggravates atherosclerosis".

PMID- 21172872
TI  - Altered peptide ligands make their entry.

PMID- 21172873
TI  - Pillars article: separation of IL-4 production from Th cell proliferation by an
      altered T cell receptor ligand. Science. 1991. 252: 1308-1310.

PMID- 21172874
TI  - The role of osteoclast-associated receptor in osteoimmunology.
AB  - The term osteoimmunology is coined for molecular and cellular cross talk between
      the skeletal and immune system. Immunomodulatory signals have long been
      implicated as key regulators of bone metabolism. Recently, osteoclast-associated
      receptor (OSCAR), an IgG-like receptor, has been identified as an important
      osteoimmunological mediator. OSCAR expression in bone is highly conserved across
      different species, and the molecule is an important costimulatory receptor for
      osteoclast differentiation through activation of NFATc1. In humans, OSCAR is
      expressed by macrophages, monocytes, and monocyte-derived dendritic cells and
      modulates the response of the innate and adaptive immune systems by promoting
      cell activation and maturation, Ag presentation, and proinflammatory circuits.
      Human studies indicate that OSCAR may contribute to the pathogenesis and severity
      of osteoporosis and rheumatoid arthritis. In this paper, we review the structure
      function relationship, expression pattern, and physiological role of OSCAR in
      osteoimmunology and summarize its potential implications for human diseases.

PMID- 21172875
TI  - Adaptive clinical trials: the promise and the caution.

PMID- 21172876
TI  - Familial lung adenocarcinoma caused by the EGFR V843I germ-line mutation.

PMID- 21172878
TI  - Primary tracheal non-Hodgkin's lymphoma.

PMID- 21172877
TI  - Racial differences in chronic immune stimulatory conditions and risk of non
      Hodgkin's lymphoma in veterans from the United States.
AB  - PURPOSE: To examine underlying etiologic factors that may explain the racial
      disparity in non-Hodgkin's lymphoma (NHL) incidence patterns. PATIENTS AND
      METHODS: We assessed immune-related conditions and risk of developing NHL among
      more than 4 million hospitalized US veterans including 9,496 patients with NHL
      (7,999 white patients and 1,497 black patients) with up to 26 years of follow-up.
      We used time-dependent Poisson regression to estimate rate ratios (RRs) and 95%
      CIs for NHL risk among patients with a history of specific autoimmune diseases,
      infections, and allergies compared with patients without such history, adjusting
      for attained age, calendar year, race, number of hospital visits, and time
      between study entry and exit. RESULTS: Patients with infectious conditions had an
      increased risk of developing NHL (RR, 1.2; 95% CI, 1.1 to 1.2), particularly for
      gastrohepatic, genital, and systemic infectious conditions. Patients with
      autoimmune disease were generally more likely to develop NHL than patients
      without autoimmune disease, especially for conditions that typically present with
      detectable autoantibodies with systemic involvement (RR, 2.0; 95% CI, 1.8 to
      2.2). Allergies were also associated with increased risk (RR, 1.4; 95% CI, 1.3 to
      1.5). Although the risk of NHL was lower for blacks than whites (RR, 0.87; 95%
      CI, 0.82 to 0.92), blacks had a slightly higher risk of NHL associated with
      infections than whites (likelihood ratio test, P = .002) and a tendency toward
      higher risk associated with allergies (likelihood ratio test, P = .05). Risks
      associated with autoimmune conditions were similar by race (likelihood ratio
      test, P = .5). CONCLUSION: The observed difference in NHL risk by race supports a
      role for race-related differences in genes regulating immune/inflammatory
      response.

PMID- 21172879
TI  - Excellent outcome with reduced treatment in infants with nonmetastatic and
      unresectable neuroblastoma without MYCN amplification: results of the prospective
      INES 99.1.
AB  - PURPOSE: To evaluate the efficacy of low-dose chemotherapy in infants with
      nonmetastatic and unresectable neuroblastoma (NB) without MYCN amplification.
      PATIENTS AND METHODS: Infants with localized NB and no MYCN amplification were
      eligible in the SIOPEN Infant Neuroblastoma European Study 99.1 study. Primary
      tumor was deemed unresectable according to imaging defined risk factors.
      Diagnostic procedures and staging were carried out according to International
      Staging System recommendations. Children without threatening symptoms received
      low-dose cyclophosphamide (5 mg/kg/d * 5 days) and vincristine (0.05 mg/kg at day
      1; CyV), repeated once to three times every 2 weeks until surgical excision could
      be safely performed. Children with either one threatening symptom or insufficient
      response to CyV were given carboplatin and etoposide (CaE), sometimes followed by
      vincristine, cyclophosphamide, and doxorubicin. No postoperative treatment was to
      be administered. RESULTS: Between December 1999 and April 2004, 120 infants were
      included in the study. Eighty-eight had no threatening symptoms and 79 received
      CyV. CaE was given to 49 of them because of insufficient response. Thirty-two
      children had threatening symptoms, 30 of whom received CaE. Anthracyclines were
      given to 46 children. Surgery was attempted in 102 patients, leading to gross
      surgical excision in 93. Relapse occurred in 12 patients (nine local and three
      metastatic). Five-year overall and event-free survivals were 99% +/- 1% and 90%
      +/- 3%, respectively, with a median follow-up of 6.1 years (range, 1.6 to 9.1).
      CONCLUSION: Low-dose chemotherapy without anthracyclines is effective in 62% of
      infants with an unresectable NB and no MYCN amplification, allowing excellent
      survival rates without jeopardizing their long-term outcome.

PMID- 21172880
TI  - Delayed hepatic metastasis from a benign fibroblastic meningioma thirty-one years
      after surgical resection of the intracranial tumor.

PMID- 21172881
TI  - Trastuzumab-DM1: building a chemotherapy-free road in the treatment of human
      epidermal growth factor receptor 2-positive breast cancer.

PMID- 21172882
TI  - Outcome--adaptive randomization: is it useful?
AB  - Outcome-adaptive randomization is one of the possible elements of an adaptive
      trial design in which the ratio of patients randomly assigned to the experimental
      treatment arm versus the control treatment arm changes from 1:1 over time to
      randomly assigning a higher proportion of patients to the arm that is doing
      better. Outcome-adaptive randomization has intuitive appeal in that, on average,
      a higher proportion of patients will be treated on the better treatment arm (if
      there is one). In both the randomized phase II and phase III settings with a
      short-term binary outcome, we compare outcome-adaptive randomization with designs
      that use 1:1 and 2:1 fixed-ratio randomizations (in the latter, twice as many
      patients are randomly assigned to the experimental treatment arm). The
      comparisons are done in terms of required sample sizes, the numbers and
      proportions of patients having an inferior outcome, and we restrict attention to
      the situation in which one treatment arm is a control treatment (rather than the
      less common situation of two experimental treatments without a control
      treatment). With no differential patient accrual rates because of the trial
      design, we find no benefits to outcome-adaptive randomization over 1:1
      randomization, and we recommend the latter. If it is thought that the patient
      accrual rates will be substantially higher because of the possibility of a higher
      proportion of patients being randomly assigned to the experimental treatment
      (because the trial will be more attractive to patients and clinicians), we
      recommend using a fixed 2:1 randomization instead of an outcome-adaptive
      randomization.

PMID- 21172883
TI  - Bilateral adrenal medullary hyperplasia associated with an SDHB mutation.

PMID- 21172885
TI  - Gemtuzumab ozogamicin: one size does not fit all--the case for personalized
      therapy.

PMID- 21172884
TI  - Durable remission of metastatic renal cell carcinoma with gemcitabine and
      capecitabine after failure of targeted therapy.

PMID- 21172886
TI  - Influence of sex hormones on melanoma.

PMID- 21172887
TI  - Total therapy 2 in treatment of multiple myeloma: questions about gene expression
      profiling and treatment-related mortality.

PMID- 21172888
TI  - Clinical significance of hepatitis B virus (HBV)-DNA monitoring to detect HBV
      reactivation after systemic chemotherapy.

PMID- 21172889
TI  - Recurrent glioblastoma: not only surgery.

PMID- 21172890
TI  - Improved prognosis for older adolescents with acute lymphoblastic leukemia.
AB  - PURPOSE: The prognosis for older adolescents and young adults with acute
      lymphoblastic leukemia (ALL) has been historically much worse than that for
      younger patients. We reviewed the outcome of older adolescents (age 15 to 18
      years) treated in four consecutive Total Therapy studies to determine if recent
      improved treatment extended to this high-risk group. PATIENTS AND METHODS:
      Between 1991 and 2007, 963 pediatric patients, including 89 older adolescents,
      were enrolled on Total Therapy studies XIIIA, XIIIB, XIV, and XV. In the first
      three studies, treatment selection was based on presenting clinical features and
      leukemic cell genetics. In study XV, the level of residual disease was used to
      guide treatment, which featured intensive methotrexate, glucocorticoid,
      vincristine, and asparaginase, as well as early triple intrathecal therapy for
      higher-risk ALL. RESULTS: The 89 older adolescents were significantly more likely
      to have T-cell ALL, the t(4;11)(MLL-AF4), and detectable minimal residual disease
      during or at the end of remission induction; they were less likely to have the
      t(12;21)(ETV6-RUNX1) compared with younger patients. In the first three studies,
      the 44 older adolescents had significantly poorer event-free survival and overall
      survival than the 403 younger patients. This gap in prognosis was abolished in
      study XV: event-free survival rates at 5 years were 86.4% +/- 5.2% (standard
      error) for the 45 older adolescents and 87.4% +/- 1.7% for the 453 younger
      patients; overall survival rates were 87.9% +/- 5.1% versus 94.1% +/- 1.2%,
      respectively. CONCLUSION: Most older adolescents with ALL can be cured with risk
      adjusted intensive chemotherapy without stem-cell transplantation.

PMID- 21172891
TI  - Identification of patients with acute myeloblastic leukemia who benefit from the
      addition of gemtuzumab ozogamicin: results of the MRC AML15 trial.
AB  - PURPOSE: Antibody-directed chemotherapy for acute myeloid leukemia (AML) may
      permit more treatment to be administered without escalating toxicity. Gemtuzumab
      ozogamicin (GO) is an immunoconjugate between CD33 and calicheamicin that is
      internalized when binding to the epitope. We previously established that it is
      feasible to combine GO with conventional chemotherapy. We now report a large
      randomized trial testing the addition of GO to induction and/or consolidation
      chemotherapy in untreated younger patients. PATIENTS AND METHODS: In this open
      label trial, 1,113 patients, predominantly younger than age 60 years, were
      randomly assigned to receive a single dose of GO (3 mg/m(2)) on day 1 of
      induction course 1 with one of the following three induction schedules:
      daunorubicin and cytarabine; cytarabine, daunorubicin, and etoposide; or
      fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin.
      In remission, 948 patients were randomly assigned to GO in course 3 in
      combination with amsacrine, cytarabine, and etoposide or high-dose cytarabine.
      The primary end points were response rate and survival. RESULTS: The addition of
      GO was well tolerated with no significant increase in toxicity. There was no
      overall difference in response or survival in either induction of consolidation.
      However, a predefined analysis by cytogenetics showed highly significant
      interaction with induction GO (P = .001), with significant survival benefit for
      patients with favorable cytogenetics, no benefit for patients with poor-risk
      disease, and a trend for benefit in intermediate-risk patients. An internally
      validated prognostic index identified approximately 70% of patients with a
      predicted benefit of 10% in 5-year survival. CONCLUSION: A substantial proportion
      of younger patients with AML have improved survival with the addition of GO to
      induction chemotherapy with little additional toxicity.

PMID- 21172892
TI  - Quality of life after breast cancer diagnosis and survival.
AB  - PURPOSE: To examine the association of quality of life (QOL) after diagnosis of
      breast cancer with mortality and recurrence. PATIENTS AND METHODS: From 2002 to
      2004, a total of 2,230 breast cancer survivors completed the General Quality of
      Life Inventory-74 6 months after diagnosis as part of the Shanghai Breast Cancer
      Survivor Study. Also collected at baseline was information on demographic and
      clinical characteristics. At 36 months postdiagnosis, 1,845 of these women were
      re-evaluated for QOL. Outcomes were ascertained by in-person interview and record
      linkage to the vital statistics registry. The association of QOL with total
      mortality and cancer recurrence was assessed by using Cox regression analysis.
      RESULTS: During a median follow-up of 4.8 years after the 6-month postdiagnosis
      QOL assessment, 284 deaths were identified. Recurrence was documented in 267
      patients after 108 patients with stage IV breast cancer or recurrence before
      study enrollment were excluded. Women with the highest tertile of social well
      being QOL score, compared with those with the lowest score, had a 38% decreased
      risk of mortality (95% CI, 0.46 to 0.85; P for trend = .002) and a 48% decreased
      risk of breast cancer recurrence (95% CI, 0.38 to 0.71; P for trend < .001). QOL
      assessed at 36 months postdiagnosis was not significantly associated with
      subsequent risk of mortality or recurrence. CONCLUSION: Social well-being in the
      first year after cancer diagnosis is a significant prognostic factor for breast
      cancer recurrence or mortality, suggesting a possible avenue of intervention by
      maintaining or enhancing social support for women soon after their breast cancer
      diagnosis to improve disease outcomes.

PMID- 21172894
TI  - Inclusion of tumor biology molecular markers to improve the ductal carcinoma in
      situ ipsilateral breast tumor recurrence nomogram predictability.

PMID- 21172893
TI  - Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment
      of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after
      prior HER2-directed therapy.
AB  - PURPOSE: The antibody-drug conjugate trastuzumab-DM1 (T-DM1) combines the
      biologic activity of trastuzumab with targeted delivery of a potent
      antimicrotubule agent, DM1, to human epidermal growth factor receptor 2 (HER2)
      overexpressing cancer cells. Based on results from a phase I study that showed T
      DM1 was well tolerated at the maximum-tolerated dose of 3.6 mg/kg every 3 weeks,
      with evidence of efficacy, in patients with HER2-positive metastatic breast
      cancer (MBC) who were previously treated with trastuzumab, we conducted a phase
      II study to further define the safety and efficacy of T-DM1 in this patient
      population. PATIENTS AND METHODS: This report describes a single-arm phase II
      study (TDM4258g) that assessed efficacy and safety of intravenous T-DM1 (3.6
      mg/kg every 3 weeks) in patients with HER2-positive MBC who had tumor progression
      after prior treatment with HER2-directed therapy and who had received prior
      chemotherapy. RESULTS: With a follow-up of >= 12 months among 112 treated
      patients, the objective response rate by independent assessment was 25.9% (95%
      CI, 18.4% to 34.4%). Median duration of response was not reached as a result of
      insufficient events (lower limit of 95% CI, 6.2 months), and median progression
      free survival time was 4.6 months (95% CI, 3.9 to 8.6 months). The response rates
      were higher among patients with confirmed HER2-positive tumors
      (immunohistochemistry 3+ or fluorescent in situ hybridization positive) by
      retrospective central testing (n = 74). Higher response rates were also observed
      in patients whose tumors expressed >= median HER2 levels by quantitative reverse
      transcriptase polymerase chain reaction for HER2 expression, compared with
      patients who had less than median HER2 levels. T-DM1 was well tolerated with no
      dose-limiting cardiotoxicity. Most adverse events (AEs) were grade 1 or 2; the
      most frequent grade >= 3 AEs were hypokalemia (8.9%), thrombocytopenia (8.0%),
      and fatigue (4.5%). CONCLUSION: T-DM1 has robust single-agent activity in
      patients with heavily pretreated, HER2-positive MBC and is well tolerated at the
      recommended phase II dose.

PMID- 21172895
TI  - Curious case of combined small- and squamous cell carcinoma.

PMID- 21172896
TI  - Looking at the seemingly contradictory role of vinblastine in anaplastic large
      cell lymphoma from a metronomic perspective.

PMID- 21172897
TI  - Activation of pulmonary invariant NKT cells leads to exacerbation of acute lung
      injury caused by LPS through local production of IFN-gamma and TNF-alpha by Gr-1+
      monocytes.
AB  - Invariant NK T (iNKT) cells are known to play a critical role in the regulation
      of inflammatory responses in various clinical settings. In the present study, we
      assessed the contribution of iNKT cells to the development of acute lung injury
      (ALI), which was caused by intra-tracheal administration of LPS. Jalpha18 gene
      disrupted mice lacking these cells underwent neutrophilic inflammatory responses
      in lungs at an equivalent level as control mice. Next, mice were sensitized intra
      tracheally with alpha-galactosylceramide, an activator of iNKT cells, followed by
      challenge with LPS. In this model, mice showed severe lung injury, and all mice
      were killed within 72 h after LPS injection. IFN-gamma and tumor necrosis factor
      (TNF)-alpha were strikingly elevated in the lungs of these mice. Administration
      of neutralizing mAb against IFN-gamma and TNF-alpha attenuated lung injury in a
      histopathological analysis and improved their survival rate. Flow cytometric
      analysis revealed that IFN-gamma was expressed in NK cells, iNKT cells and also
      Gr-1(dull+)Ly-6C(+) monocytes and TNF-alpha was detected mainly in Gr
      1(bright+)Ly-6G(+) neutrophils and Gr-1(dull+)Ly-6C(+) monocytes. Otherwise, in
      mice treated with LPS alone, IFN-gamma was not detected in the lungs and Gr
      1(bright+)Ly-6G(+) neutrophil was a main cellular source of TNF-alpha production.
      Anti-Gr-1 mAb resulted in the attenuation of ALI and decrease in the level of
      these cytokines. These results indicated that activation of iNKT cells led to
      striking exacerbation of ALI caused by LPS and that Gr-1(+) monocytes were
      recruited in the lungs with expressing IFN-gamma and TNF-alpha and played an
      important role in the development of these responses.

PMID- 21172898
TI  - Preparing coordinated eye and hand movements: dual-task costs are not
      attentional.
AB  - Dual-task costs are observed when people perform two tasks at the same time. It
      has been suggested that these costs arise from limitations of movement goal
      selection when multiple goal-directed movements are made simultaneously. To
      investigate this, we asked participants to reach and look at different locations
      while we varied the time between the cues to start the eye and the hand movement
      between 150 ms and 900 ms. In Experiment 1, participants executed the reach
      first, and the saccade second, in Experiment 2 the order of the movements was
      reversed. We observed dual-task costs-participants were slower to start the eye
      or hand movement if they were planning another movement at that time. In
      Experiment 3, we investigated whether these dual-task costs were due to limited
      attentional resources needed to select saccade and reach goal locations. We found
      that the discrimination of a probe improved at both saccade and reach locations,
      indicating that attention shifted to both movement goals. Importantly, while we
      again observed the expected dual-task costs as reflected in movement latencies,
      there was no apparent delay of the associated attention shifts. Our results rule
      out attentional goal selection as the causal factor leading to the dual-task
      costs occurring in eye-hand movements.

PMID- 21172900
TI  - Visual motion, eye motion, and relative motion: A parametric fMRI study of
      functional specializations of smooth pursuit eye movement network areas.
AB  - The ability to pursue moving objects with the eyes is vital to humans. However,
      it remains unclear how the brain differentiates visual object motion, smooth
      pursuit eye movements (SPEM), and eye movement-induced relative motion on the
      retina and where visual-to-oculomotor transformation takes place. To characterize
      functional differences of SPEM-processing cortical areas, we simultaneously
      measured functional magnetic resonance imaging (fMRI) and smooth pursuit to
      visual, oculomotor, and visuo-oculomotor stimuli varying the quantity of
      background dots of the stimuli. Resulting activations involved the whole visuo
      oculomotor network. They varied among regions depending on the functional tasks
      and parametric changes of the background. Activation in many SPEM regions
      increased from 1 to 16 background dots but decreased at 36 dots. This could be an
      effect of coherent-texture perception. Putative MST area was not influenced by
      the amount of moving or stationary background dots. It probably participates in
      visuo-oculomotor transformation. Parts of the posterior parietal cortex seem
      specifically activated with relative motion between eye and background, but not
      with motion per se. This could be important for the perception of spatial
      references.

PMID- 21172901
TI  - Drug treatment of scrub typhus.
AB  - Scrub typhus is a vector-borne disease caused by the pathogen Orientia
      tsutsugamushi. We review the published literature for evidence on drug treatment
      in scrub typhus. Doxycycline has a proven efficacy in several trials and a meta
      analysis, although resistance has been documented in parts of northern Thailand.
      Macrolides are equally efficacious and have less adverse effects, but they are
      expensive. Azithromycin is the recommended drug in pregnancy and for children.
      Rifampicin is effective in areas where doxycycline resistance is present.
      Quinolones have shown some degree of efficacy but the evidence is scant. Most
      clinical evidence on drug treatment is from cases of mild-to-moderate scrub
      typhus. Further study is needed on the efficacy of different antibiotics in the
      treatment of severe, life-threatening scrub typhus.

PMID- 21172899
TI  - Motion-induced blindness and microsaccades: cause and effect.
AB  - It has been suggested that subjective disappearance of visual stimuli results
      from a spontaneous reduction of microsaccade rate causing image stabilization,
      enhanced adaptation, and a consequent fading. In motion-induced blindness (MIB),
      salient visual targets disappear intermittently when surrounded by a moving
      pattern. We investigated whether changes in microsaccade rate can account for
      MIB. We first determined that the moving mask does not affect microsaccade
      metrics (rate, magnitude, and temporal distribution). We then compared the
      dynamics of microsaccades during reported illusory disappearance (MIB) and
      physical disappearance (Replay) of a salient peripheral target. We found large
      modulations of microsaccade rate following perceptual transitions, whether
      illusory (MIB) or real (Replay). For MIB, the rate also decreased prior to
      disappearance and increased prior to reappearance. Importantly, MIB persisted in
      the presence of microsaccades although sustained microsaccade rate was lower
      during invisible than visible periods. These results suggest that the
      microsaccade system reacts to changes in visibility, but microsaccades also
      modulate MIB. The latter modulation is well described by a Poisson model of the
      perceptual transitions assuming that the probability for reappearance and
      disappearance is modulated following a microsaccade. Our results show that
      microsaccades counteract disappearance but are neither necessary nor sufficient
      to account for MIB.

PMID- 21172902
TI  - A survey of neonatal tetanus at a district general hospital in north-east
      Nigeria.
AB  - Neonatal tetanus (NNT) remains among the leading causes of morbidity and
      mortality in Nigeria and a huge challenge in achieving the fourth goal of the
      Millennium Development Goals. We reviewed the morbidity and mortality pattern
      among neonates with NNT admitted to the District General Hospital in north-east
      Nigeria from 2006 to 2009. Half of the patients were from rural areas and were
      delivered at home by untrained traditional birth attendants with no prior
      antenatal health care. Razor blades and scissors were the instruments used to cut
      the cord in nonhygienic conditions. Spasticity, lack of sucking, trismus, fever,
      omphalitis, risus sardonicus and opisthotonus were the most common presenting
      signs and symptoms. Overall, mortality was 56%. Health education of mothers and
      traditional birth attendants, the promotion of hospital delivery and antenatal
      tetanus immunization of all pregnant women, particularly in rural areas, are
      recommended if NNT is to be prevented.

PMID- 21172903
TI  - Sporotrichosis in Delhi among the migrant population from Uttarakhand, India.
AB  - Six cases of sporotrichosis in Delhi (non-endemic area) were recorded in migrants
      from Uttarakhand over a period of one year (2008-2009). The clinico
      epidemiological and mycological profile of the patients is discussed. These were
      confirmed by mycological culture, histopathological examination and/or remission
      of lesion with potassium iodide. Sporotrichosis is endemic in Uttarakhand, a
      north-western state in the sub-Himalayan region.

PMID- 21172904
TI  - Rapid tranquillization agents for severe behavioural disturbance: a survey of
      African psychiatrists' prescription patterns.
AB  - Guidelines on the use of rapid tranquillizers for severe behavioural disturbance
      have changed over the last six decades. This survey reports a minimal change in
      the prescription patterns among psychiatrists sampled from Africa. Parenteral
      chlorpromazine and diazepam are still commonly prescribed, the least being
      intramuscular lorazepam, olanzapine and promethazine. Respondents indicated that
      drug availability was more likely than prescription preference or cost to
      influence their choices. They were also equally concerned about the
      tranquillizer's side effects, its ability to provide rapid and sustained sedation
      and its ability to calm a patient while awaiting psychiatric assessment.

PMID- 21172905
TI  - Disability profile in leprosy patients' diagnoses in a rural reference leprosy
      centre in Ethiopia during 1999-2009.
AB  - We assessed the epidemiology of disabilities in leprosy cases treated in a rural
      hospital over a 10-year period. This is a retrospective data collection using
      leprosy registers and treatment cards in a rural private mission hospital. Over
      the 10-year period, 210 patients with leprosy were registered for treatment. One
      hundred and twenty-eight (61.5%) had disabilities (26.0% grade 1 and 35.6% grade
      2): 13.5% ocular disabilities, 44.5% disabilities in hands and 44.7% foot
      impairment. Patients >19 years had more disabilities (66.7% versus 50.7%) (P =
      0.03), especially ocular disabilities (16.7% in >20 versus 6.0% in <20 years) (P
      = 0.03). This study detected a high prevalence of disabilities.

PMID- 21172906
TI  - Exposure to kynurenic acid during adolescence produces memory deficits in
      adulthood.
AB  - The glia-derived molecule kynurenic acid (KYNA) is an antagonist of alpha7
      nicotinic acetylcholine receptors and the glycine(B) binding site on n-methyl-d
      aspartateglutamate receptors, both of which have critical roles in neural
      plasticity as well as learning and memory. KYNA levels are increased in the
      brains and cerebral spinal fluid of persons with schizophrenia, leading to the
      notion that changes in KYNA concentration might contribute to cognitive
      dysfunction associated with this disorder. Indeed, recent studies indicate that
      increasing endogenous KYNA concentration by administering l-kynurenine (L-KYN,
      the precursor of KYNA) impairs spatial as well as contextual learning and memory
      in adult rats. In the present study, rats were treated with L-KYN (100 mg/kg)
      throughout adolescence to increase endogenous KYNA concentration during this
      critical time in brain development. Rats were then tested drug-free as adults to
      test the hypothesis that exposure to elevated levels of KYNA during development
      may contribute to cognitive dysfunction later in life. Consistent with prior
      studies in which adult rats were treated acutely with L-KYN, juvenile rats
      exposed to increased KYNA concentration during adolescence exhibited deficits in
      contextual fear memory, but cue-specific fear memory was not impaired. In
      addition, rats treated with L-KYN as adolescents were impaired on a novel object
      recognition memory task when tested as adults. The memory deficits could not be
      explained by drug-induced changes in locomotor activity or shock sensitivity.
      Together, these findings add to the growing literature supporting the notion that
      exposure to increased concentration of KYNA may contribute to cognitive deficits
      typically observed in schizophrenia.

PMID- 21172907
TI  - Pharmacokinetic modeling and [123]5-IA-85380 single photon emission computed
      tomography imaging in baboons: optimization of dosing regimen for ABT-089.
AB  - Neuronal acetylcholine nicotinic receptors (nAChRs) are targets for the
      development of novel treatments of brain diseases. However, adverse effects (for
      example, emesis or nausea) associated with high drug maximal exposures or C(max)
      at nAChRs often hinder the advancement of experimental compounds in clinical
      trials. Therefore, it is essential to explore the feasibility of maintaining
      exposures below a predetermined C(max) while sustaining targeted CNS effects. By
      use of a [123I]5-IA [5-[123I]iodo-3-[2(S)-azetidinylmethoxy]pyridine]
      displacement SPECT imaging paradigm in nonhuman primates, we compared brain nAChR
      binding activity elicited by either a bolus injection or by slow infusion of an
      identical dose of a novel neuronal nicotinic agonist, ABT-089 [2-methyl-3-(2-(S)
      pyrrolidinylmethoxy)pyridine dihydrochloride], where the slow infusion scheme was
      derived from a two-compartment pharmacokinetic modeling designed to limit the
      C(max). We determined [123I]5-IA displacement using doses of ABT-089 (0.04, 0.4,
      and 1.0 mg/kg i.v.) that encompassed efficacious drug exposures in nonhuman
      primates and examined the relationship between ABT-089 displacement ratios and
      plasma exposures. Our results indicated that calculated displacement ratios were
      quite similar between the two different dosing regimens despite substantial
      differences in C(max). In addition, displacement ratios correlated well with drug
      exposures calculated as the area-under-curve (AUC) of plasma concentration and
      varied in a dose-dependent manner, suggesting that displacement ratios are driven
      by the AUC of drug plasma exposure but not C(max). Our data demonstrate the
      feasibility of predicting plasma exposures using a two-compartment
      pharmacokinetic model and its potential for optimizing dosing regimens.

PMID- 21172908
TI  - Awake rat pharmacological magnetic resonance imaging as a translational
      pharmacodynamic biomarker: metabotropic glutamate 2/3 agonist modulation of
      ketamine-induced blood oxygenation level dependence signals.
AB  - Neuroimaging techniques have been exploited to characterize the effect of N
      methyl-d-aspartate (NMDA) receptor antagonists on brain activation in humans and
      animals. However, most preclinical imaging studies were conducted in anesthetized
      animals and could be confounded by potential drug-anesthetic interactions as well
      as anesthetic agents' effect on brain activation, which may affect the
      translation of these basic research findings to the clinical setting. The main
      aim of the current study was to examine the brain activation elicited by the
      infusion of a subanesthetic dose of ketamine using blood oxygenation level
      dependence (BOLD) pharmacological magnetic resonance imaging (phMRI) in awake
      rats. However, a secondary aim was to determine whether a behaviorally active
      metabotropic glutamate 2/3 receptor agonist, (1S,2R,5R,6R)-2-amino-4
      oxabicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY379268), could modulate the
      effects of ketamine-induced brain activation. Our data indicate that ketamine
      produces positive BOLD signals in several cortical and hippocampal regions,
      whereas negative BOLD signals were observed in regions, such as periaqueductal
      gray (PAG) (p < 0.05). Furthermore, pretreatment of LY379268 significantly
      attenuated ketamine-induced brain activation in a region-specific manner
      (posterior cingulate, entorhinal, and retrosplenial cortices, hippocampus CA1,
      and PAG). The [corrected] region-specific brain activations observed in this
      ketamine phMRI study may afford a method of confirming central activity and dose
      selection in early clinical trials for novel experimental therapeutics.
      [corrected]

PMID- 21172909
TI  - Endothelium-dependent vasodilation in human mesenteric artery is primarily
      mediated by myoendothelial gap junctions intermediate conductance calcium
      activated K+ channel and nitric oxide.
AB  - Myoendothelial microdomain signaling via localized calcium-activated potassium
      channel (K(Ca)) and gap junction connexins (Cx) is critical for endothelium
      dependent vasodilation in rat mesenteric artery. The present study determines the
      relative contribution of NO and gap junction-K(Ca) mediated microdomain signaling
      to endothelium-dependent vasodilation in human mesenteric artery. The hypothesis
      tested was that such activity is due to NO and localized K(Ca) and Cx activity.
      In mesenteric arteries from intestinal surgery patients, endothelium-dependent
      vasodilation was characterized using pressure myography with pharmacological
      intervention. Vessel morphology was examined using immunohistochemical and
      ultrastructural techniques. In vessel segments at 80 mm Hg, the intermediate
      (I)K(Ca) blocker 1-[(2-chlorophenyl)diphenyl-methyl]-1H-pyrazole (TRAM-34; 1 MUM)
      inhibited bradykinin (0.1 nM-3 MUM)-induced vasodilation, whereas the small (S)
      K(Ca) blocker apamin (50 and 100 nM) had no effect. Direct IK(Ca) activation with
      1-ethyl-2-benzimidazolinone (1-EBIO; 10-300 MUM) induced vasodilation, whereas
      cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (1-30
      MUM), the SK(Ca) activator, failed to dilate arteries, whereas dilation induced
      by 1-EBIO (10-100 MUM) was blocked by TRAM-34. Bradykinin-mediated vasodilation
      was attenuated by putative gap junction block with carbenoxolone (100 MUM), with
      remaining dilation blocked by N-nitro l-arginine methyl ester (100 MUM) and [1H
      [1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one] (10 MUM), NO synthase and soluble
      guanylate cyclase blockers, respectively. In human mesenteric artery,
      myoendothelial gap junction and IK(Ca) activity are consistent with Cx37 and
      IK(Ca) microdomain expression and distribution. Data suggest that endothelium
      dependent vasodilation is primarily mediated by NO, IK(Ca), and gap junction Cx37
      in this vessel. Myoendothelial microdomain signaling sites are present in human
      mesenteric artery and are likely to contribute to endothelium-dependent
      vasodilation via a mechanism that is conserved between species.

PMID- 21172910
TI  - Functional integration of a metabolic network model and expression data without
      arbitrary thresholding.
AB  - MOTIVATION: Flux balance analysis (FBA) has been used extensively to analyze
      genome-scale, constraint-based models of metabolism in a variety of organisms.
      The predictive accuracy of such models has recently been improved through the
      integration of high-throughput expression profiles of metabolic genes and
      proteins. However, extensions of FBA often require that such data be discretized
      a priori into sets of genes or proteins that are either 'on' or 'off'. This
      procedure requires selecting relatively subjective expression thresholds, often
      requiring several iterations and refinements to capture the expression dynamics
      and retain model functionality. RESULTS: We present a method for mapping
      expression data from a set of environmental, genetic or temporal conditions onto
      a metabolic network model without the need for arbitrary expression thresholds.
      Metabolic Adjustment by Differential Expression (MADE) uses the statistical
      significance of changes in gene or protein expression to create a functional
      metabolic model that most accurately recapitulates the expression dynamics. MADE
      was used to generate a series of models that reflect the metabolic adjustments
      seen in the transition from fermentative- to glycerol-based respiration in
      Saccharomyces cerevisiae. The calculated gene states match 98.7% of possible
      changes in expression, and the resulting models capture functional
      characteristics of the metabolic shift. AVAILABILITY: MADE is implemented in
      Matlab and requires a mixed-integer linear program solver. Source code is freely
      available at http://www.bme.virginia.edu/csbl/downloads/.

PMID- 21172911
TI  - Fast tomographic reconstruction on multicore computers.
AB  - SUMMARY: Tomo3D implements a multithreaded vectorized approach to tomographic
      reconstruction that takes full advantage of the computer power in modern
      multicore computers. Full resolution tomograms are generated at high speed on
      standard computers with no special system requirements. Tomo3D has the most
      common reconstruction methods implemented, namely weighted Back-projection (WBP)
      and simultaneous iterative reconstruction technique (SIRT). It proves to be
      competitive with current graphic processor unit solutions in terms of processing
      time, in the order of a few seconds with WBP or minutes with SIRT. The program is
      compatible with standard packages, which easily allows integration in the
      electron tomography workflow.

PMID- 21172912
TI  - Statistical analysis of the cancer cell's molecular entropy using high-throughput
      data.
AB  - MOTIVATION: As cancer progresses, DNA copy number aberrations accumulate and the
      genomic entropy (chromosomal disorganization) increases. For this surge to have
      any oncogenetic effect, it should (to some extent) be reflected at other
      molecular levels of the cancer cell, in particular that of the transcriptome.
      Such a coincidence of cancer progression and the propagation of an entropy
      increase through the molecular levels of the cancer cell would enhance the
      understanding of cancer evolution. RESULTS: A statistical argument reveals that
      (under some assumptions) an entropy increase in one random variable (DNA copy
      number) leads to an entropy increase in another (gene expression). Statistical
      methodology is provided to investigate the relation between the genomic and
      transcriptomic entropy using high-throughput data. Analyses of multiple high
      throughput datasets using this methodology show a close, concordant relation
      among the genomic and transcriptomic entropy. Hence, as cancer evolves, and the
      genomic entropy increases, the transcriptomic entropy is also expected to surge.

PMID- 21172913
TI  - The doctors say no.

PMID- 21172915
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 1. Nicardipine hydrochloride for hypertensive crisis in patients
      with aortic dissection.

PMID- 21172917
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 2. Hypertonic sodium solutions versus mannitol in reducing ICP in
      traumatic brain injury.

PMID- 21172918
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 3. Rapid tranquilisation in acute psychotic agitation.

PMID- 21172919
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 4. Timing of antibiotic administration in community-acquired
      pneumonia.

PMID- 21172921
TI  - The involvement of users and carers in health and social research: the realities
      of inclusion and engagement.
AB  - In this article we explore the challenges to researchers intending to involve
      vulnerable populations in health and social care research, and provide evidence
      based recommendations to support the proactive inclusion of these populations in
      the research process. We provide a rationale for the study, followed by the
      introduction and descriptions of our research experiences (presented as two case
      studies) to provide a contextual backcloth for the discussion.We highlight the
      inherent challenges in empowering vulnerable populations in research, based on
      the combination of our own and other people's experiences. Collectively, these
      illustrate and underpin practice issues, relate theory to practice in a
      meaningful way, and facilitate the recognition of the realities in future
      development in this important area of involving users and carers. We conclude by
      providing recommendations for future practice and research development from a
      wider, international perspective.

PMID- 21172922
TI  - A self-report instrument that describes urogenital atrophy symptoms in breast
      cancer survivors.
AB  - Urogenital atrophy affects the lower urinary and genital tracts and is
      responsible for urinary, genital, and sexual symptoms. The accurate
      identification, measurement, and documentation of symptoms are limited by the
      absence of reliable and valid instruments. The Urogenital Atrophy Questionnaire
      was developed to allow self-reporting of symptoms and to provide clinicians and
      researchers an instrument to identify, measure, and document indicators of
      urogenital atrophy. A pilot study (n = 30) measured test-retest reliability (p <
      .05) of the instrument. Subsequently, a survey of women with (n = 168) and
      without breast cancer (n = 166) was conducted using the Urogenital Atrophy
      Questionnaire, Female Sexual Function Instrument, and Functional Assessment of
      Cancer Therapy, Breast, Endocrine Scale. Exploratory factor analysis (KMO 0.774;
      Bartlett's test of sphericity 0.000) indicated moderate-high relatedness of
      items. Concurrent (p > .01) and divergent validity (p < .000) were established. A
      questionnaire resulted that enables women, regardless of sexual orientation,
      partner status, and levels of sexual activity to accurately report symptoms.

PMID- 21172923
TI  - Pediatric nurses' beliefs and pain management practices: an intervention pilot.
AB  - We evaluated feasibility of the Internet-based Relieve Children's Pain (RCP)
      protocol to improve nurses' management of children's pain. RCP is an interactive,
      content-focused, and Kolb's experiential learning theory-based intervention.
      Using a one-group, pretest-posttest design, we evaluated feasibility of RCP and
      pretest-posttest difference in scores for nurses' beliefs, and simulated and
      actual pain management practices. Twenty-four RNs completed an Internet-based
      Pain Beliefs and Practices Questionnaire (PBPQ, alpha=.83) before and after they
      completed the RCP and an Acceptability Scale afterward. Mean total PBPQ scores
      significantly improved from pretest to posttest as did simulated practice scores.
      After RCP in actual hospital practice, nurses administered significantly more
      ibuprofen and ketorolac and children's pain intensity significantly decreased.
      Findings showed strong evidence for the feasibility of RCP and study procedures
      and significant improvement in nurses' beliefs and pain management practices. The
      2-hr RCP program is promising and warrants replication with an attention control
      group and a larger sample.

PMID- 21172924
TI  - Colonic ulceration as an unusual manifestation of vasculopathy in systemic
      sclerosis.

PMID- 21172925
TI  - Analysis of immune reconstitution after autologous CD34+ stem/progenitor cell
      transplantation for systemic sclerosis: predominant reconstitution of Th1 CD4+ T
      cells.
AB  - OBJECTIVE: The aim of this study is to evaluate the mechanism of long-term effect
      of autologous haematopoietic stem cell transplantation (ASCT) in treatment of
      SSc. METHODS: Eleven patients (three males and eight females) with SSc were
      enrolled. Blood mononuclear cells were harvested after mobilization treatment
      with CYC and G-CSF. CD34+ haematopoietic stem/progenitor cell fractions were
      purified and cryopreserved. Patients were transplanted with > 2 * 10(6)/kg
      autologous CD34+ cells after high-dose CYC (50 mg/kg for 4 days) conditioning.
      Immune reconstitution was evaluated serially by analysing lymphocyte
      subpopulations for 36 months. RESULTS: Progressive improvement of skin sclerosis
      has been observed for 3 years in most of the patients. The serum level of anti
      Scl-70, an auto-antibody specific to SSc, was progressively decreased after ASCT.
      Improvement of skin sclerosis was significantly associated with the change in the
      serum anti-Scl-70 level after ASCT at 36 months. Serum levels of KL-6 and
      surfactant protein D, indicators for interstitial pneumonia activity, were also
      significantly decreased. The number of CD8+ T cells immediately recovered within
      a month after ASCT, while the number of CD4+ T cells remained low for >36 months
      post-transplant. The majority of CD4+ cells were memory but not naive T cells,
      and regulatory CD4+ T cells were not recovered. Th1/Th2 ratio was significantly
      increased after ASCT. CONCLUSIONS: ASCT with purified CD34+ cells was effective
      in controlling the disease activity of SSc. Th1/Th2 ratio was significantly
      increased for at least 3 years after ASCT.

PMID- 21172927
TI  - Comment on: Efficacy and safety of various repeat treatment dosing regimens of
      rituximab in patients with active rheumatoid arthritis: results of a Phase III
      randomized study (MIRROR).

PMID- 21172929
TI  - Retinal vascular calibre is altered in patients with rheumatoid arthritis: a
      biomarker of disease activity and cardiovascular risk?
AB  - OBJECTIVES: Alterations in retinal vascular calibre, particularly wider venular
      calibre, have been independently associated with elevated markers of inflammation
      and cardiovascular risk in the general population. We hypothesized that retinal
      vascular calibre would be altered in patients with RA, who are known to have both
      elevated cardiovascular risk and chronic, systemic inflammation. METHODS: Retinal
      vascular calibre was measured from digital retinal photographs using computerized
      methods in 51 RA patients and 51 age- and gender-matched controls. Retinal
      vascular calibre was compared between RA and control patients with adjustment for
      relevant variables including cardiovascular risk factors and companion vessel
      calibre. The relationship between retinal venular calibre and inflammation was
      assessed by comparing controls and RA patients with high and lower disease
      activity. RESULTS: Retinal venular calibre [mean (s.d.)] was significantly wider
      in RA patients than in controls [235.9 (24.6) vs. 211.6 (21.0) um, P < 0.001].
      After adjustment for all relevant variables, mean venular calibre remained 20.3
      um (95% CI 10.4, 30.3) wider in RA patients compared with controls. Retinal
      venular calibre [mean (s.d.)] also increased with increasing levels of systemic
      inflammation: 211.6 (21.0) um in controls, 232.3 (22.4) um in RA patients with
      moderate or lower disease activity and 255.5 (28.3) um in RA patients with high
      disease activity (P for trend < 0.0001). CONCLUSIONS: This study demonstrates
      that RA patients have dilated retinal venular calibre, reflecting systemic
      inflammation and possibly increased cardiovascular risk. Longitudinal studies
      correlating retinal vascular calibre with subsequent cardiovascular events will
      clarify the clinical utility of this test in patients with RA.

PMID- 21172926
TI  - Advanced glycation end products induce the expression of interleukin-6 and
      interleukin-8 by receptor for advanced glycation end product-mediated activation
      of mitogen-activated protein kinases and nuclear factor-kappaB in human
      osteoarthritis chondrocytes.
AB  - OBJECTIVE: To investigate whether advanced glycation end products (AGEs) induce
      the expression of IL-6 and IL-8 through the receptor for AGEs (RAGE)-activated
      pathways in human OA chondrocytes. METHODS: OA chondrocytes were stimulated with
      AGE-modified BSA (AGE-BSA). Gene expression of IL-6 and IL-8 was quantified by
      TaqMan assays and the production was determined using ELISAs. Immunoblotting was
      used to analyse the activation of mitogen-activated protein kinases (MAPKs) and
      the degradation of IkappaBalpha. Activation of NF-kappaB was determined using an
      ELISA. Pharmacological studies to elucidate the involved pathways were executed
      using transfection with small interfering RNAs (siRNAs), inhibitors of MAPKs and
      NF-kappaB. RESULTS: AGE-BSA induced the expression of IL-6 and IL-8 in OA
      chondrocytes, which was inhibited by pre-treatment with soluble RAGE (sRAGE) or
      RAGE knockdown by siRNAs. Treatment with SB202190 (p38-MAPK inhibitor) or PD98059
      (ERK inhibitor) inhibited AGE-BSA-induced IL-6 and IL-8 expression. However,
      SP600125 (JNK inhibitor) had no effect on AGE-BSA-induced IL-6 expression but
      inhibited the expression of IL-8. Treatment with NF-kappaB inhibitors suppressed
      AGE-BSA-induced IL-6 and IL-8 expression. CONCLUSIONS: This is the first study to
      demonstrate that AGEs induce the expression of IL-6 and IL-8 in OA chondrocytes.
      A novel finding of our studies is that in OA chondrocytes, AGE-BSA-induced
      expression of IL-6, but not of IL-8, was independent of the JNK pathway.
      Activation of NF-kappaB was an absolute requirement for both IL-6 and IL-8
      expression. These results demonstrate that AGE-BSA-induced expression of IL-6 and
      IL-8 via RAGE is mediated through different MAPK signalling pathways in OA and
      possibly in other degenerative diseases.

PMID- 21172931
TI  - Development and use of the Lives Saved Tool: a model to estimate the impact of
      scaling up proven interventions on maternal, neonatal and child mortality.

PMID- 21172930
TI  - A novel regulatory circuit in base excision repair involving AP endonuclease 1,
      Creb1 and DNA polymerase beta.
AB  - DNA repair is required to maintain genome stability in stem cells and early
      embryos. At critical junctures, oxidative damage to DNA requires the base
      excision repair (BER) pathway. Since early zebrafish embryos lack the major
      polymerase in BER, DNA polymerase beta, repair proceeds via replicative
      polymerases, even though there is ample polb mRNA. Here, we report that Polb
      protein fails to appear at the appropriate time in development when AP
      endonuclease 1 (Apex), the upstream protein in BER, is knocked down. Because polb
      contains a Creb1 binding site, we examined whether knockdown of Apex affects
      creb1. Apex knockdown results in loss of Creb1 and Creb complex members but not
      Creb1 phosphorylation. This effect is independent of p53. Although both apex and
      creb1 mRNA rescue Creb1 and Polb after Apex knockdown, Apex is not a co-activator
      of creb1 transcription. This observation has broad significance, as similar
      results occur when Apex is inhibited in B cells from apex(+/-) mice. These
      results describe a novel regulatory circuit involving Apex, Creb1 and Polb and
      provide a mechanism for lethality of Apex loss in higher eukaryotes.

PMID- 21172933
TI  - Repertoires of ADHD in UK newspaper media.
AB  - This article takes a discursive approach to examine how Attention Deficit
      Hyperactivity Disorder has been represented and debated in UK newspapers in the
      last decade. Two repertoires of ADHD were identified as the biological and the
      psychosocial. Subject positions such as problem child, abnormal or ordinary
      naughty child and ineffectual or neglectful parents are embedded in these
      alternative versions of ADHD. The biological repertoire justifies and encourages
      drug treatment for problem children while the psychosocial repertoire makes
      available the subject position of ordinary naughty child and supports moral
      judgements about poor parenting practices in a 'sick society'. Such
      representations have challenged the media medicalization of ADHD common in a
      previous decade. Although the biological and the psychosocial repertoires are
      competing explanations for ADHD, they both perform a common function in
      representing families as in need of regulation.

PMID- 21172932
TI  - Cohort profile: design and methods of the PREDIMED study.

PMID- 21172934
TI  - Do traditional risk factors predict whether men who have sex with men engage in
      unprotected anal intercourse? The need for locally based research to guide
      interventions.
AB  - A great deal of research effort has been expended in an effort to identify the
      variables which most influence men who have sex with men's (MSM) unsafe sexual
      behaviors.While a set of predictor variables has emerged, these predict the
      unsafe behaviors of MSM in some locations but not in others, suggesting the need
      to investigate the predictive ability of these variables among MSM in previously
      understudied populations. Therefore, this study examined the ability of
      previously identified factors to predict unsafe sexual behaviors among MSM in
      Houston, Texas. Data were collected through a short self-report survey completed
      by MSM attending the Houston pride festival. The multiethnic participants (N =
      109) represented a range of age, educational, and income backgrounds. Fifty-seven
      percent of the survey respondents had been drunk and/or high in sexual contexts,
      19 percent evidenced alcohol dependency, 26 percent reported finding sex partners
      online and sex with serodiscordant or unknown serostatus partners was common.
      Compared to men who did not report unprotected anal intercourse (UAI) in the
      preceding two months, MSM who engaged in UAI were younger and more likely to use
      alcohol in sexual contexts, meet men online for offline sex, and perceive lower
      safer sex norms in their community. Although these results were statistically
      significant, the strength of the relationships was too small to have any
      practical value. The lack of useful explanatory power underscores the importance
      of accelerated HIV research that identifies the unique, local factors associated
      with unsafe sex in other previously understudied populations.

PMID- 21172935
TI  - Induction chemotherapy, cytoreductive surgery and intraoperative hyperthermic
      pleural irrigation in patients with stage IVA thymoma.
AB  - The optimal treatment for Masaoka stage IVA thymoma remains controversial. Whilst
      extrapleural pneumonectomy (EPP) has been proposed, we sought to examine the
      results of our institutional preference for induction chemotherapy, cytoreductive
      surgery and intraoperative hyperthermic pleural irrigation. We undertook a
      retrospective study of patients undergoing surgery for Masaoka stage IVA thymoma
      following induction chemotherapy over a three-year period at our institution.
      Between February 2007 and February 2010, 42 patients underwent surgery for
      thymoma. Six patients underwent surgery with intent to perform cytoreductive
      surgery and intraoperative hyperthermic pleural irrigation. Complete
      cytoreductive surgery was not feasible in one patient and thymectomy only was
      performed. One patient had re-operation for recurrent disease 24 months after the
      first operation and there were therefore seven procedures undertaken in six
      patients during the study period. There were no in-hospital deaths. Median follow
      up was 18.8 months (range 1.5-31.9 months). One patient died 14 months
      postoperatively from an acute cardiovascular event. The four remaining patients
      are alive and well with no evidence of disease recurrence. Multimodality therapy
      consisting of induction chemotherapy and cytoreductive surgery is a safe,
      feasible treatment for stage IVA thymoma. Our experience suggest that full
      pleurectomy is an alternative to EPP.

PMID- 21172936
TI  - Aggressive surgical strategy should be used for the treatment of thoracic aortic
      disease in patients with end-stage renal disease.
AB  - Surgery for disease of the thoracic artery in patients with end-stage renal
      disease (ESRD) depending on hemodialysis (HD) tends to be avoided because of its
      high risk. However, considering that the average survival duration after HD
      induction is increasing, the adequacy of aggressive surgical treatment of
      thoracic aneurysms was investigated. Seventeen consecutive surgeries for 16
      patients with ESRD with disease of the thoracic aorta performed between 1998 and
      2008 were analyzed retrospectively. As an intraoperative renal replacement
      therapy, prior to 2001, HD was performed in six cases and, after 2002, continuous
      hemodiafiltration (CHDF) was performed in nine cases. In two cases, no renal
      replacement therapy was performed during surgery. No operative and hospital
      mortality occurred, despite challenging indications for surgery like emergency
      setting (52.5%), history of previous aortic surgery (41.2%) and aortic arch
      surgeries (58.8%). The five-year survival rate was 62.9%. Median follow-up was
      38.8 months (1-117.6). According to this excellent outcome, surgical strategy for
      ESRD patients with disease of the thoracic aorta should be more aggressive than
      currently indicated because surgery can be safely performed by means of
      appropriate application of intraoperative HD or CHDF in order to give sufficient
      amounts of blood products and manage the water and electrolyte balance.

PMID- 21172937
TI  - Vascular endothelial growth factor in pleural fluid for differential diagnosis of
      benign and malignant origin and its clinical applications.
AB  - Our goal was to determine the role of vascular endothelial growth factor (VEGF)
      in diagnosing of pleural effusion (PE) in order to select patients deserving of
      more aggressive procedures. Seventy-nine consecutive patients with undiagnosed
      unilateral PE were enrolled. Pleural VEGF levels, measured using enzyme-linked
      immunosorbent assay (ELISA), were correlated to etiology of PEs and other markers
      (protein, lactic dehydrogenase, amylase, glucose). The median level of VEGF in
      exudates (n=65) was significantly higher than that in transudates (P=0.0001) and
      among exudates, it was significantly higher in malignant (n=49) than that in
      benign exudates (P=0.005). No significant differences were observed between
      malignant effusions due to lung cancer (n=11) and other malignant effusions
      [mesothelioma (n=13) and/or extra-thoracic cancer]. Among all variables
      evaluated, logistic regression found that only VEGF was significantly correlated
      with the presence of malignant disease (P=0.002). Analysis of the receiver
      operating characterists (ROC) curves showed that the areas under the curve of
      VEGF were significantly larger than that of amylase (P=0.02), glucose (P=0.01),
      lactic dehydrogenase (P=0.001) and protein (P=0.01). VEGF increased the
      diagnostic rate of cytological examination by 24%. VEGF may represent a helpful
      adjunct to conventional diagnostic tools in ruling out malignancy as a probable
      diagnosis, thus guiding the selection of patients who might benefit from further
      invasive procedures.

PMID- 21172938
TI  - Incidental computed tomography diagnosis of a rare triad consisting of absence of
      coronary sinus, persistent left superior vena cava, and scimitar syndrome.
AB  - We report a case of an unusual congenital triad consisting of absence of coronary
      sinus, persistent left superior vena cava and scimitar syndrome incidentally
      found in a CT-scan performed on a female complaining of exertional dyspnea.

PMID- 21172939
TI  - Does the technique of distal anastomosis influence clinical outcomes in acute
      type A aortic dissection?
AB  - The purpose of this study was to evaluate clinical outcomes of two different
      surgical techniques for the repair of acute type A dissection: open distal
      anastomosis under deep hypothermic circulatory arrest (DHCA) compared with distal
      aortic clamping on hypothermic cardiopulmonary bypass (ACPB). Between January
      2000 and July 2008, 82 patients underwent DHCA and 42 had ACPB. Major morbidity,
      operative mortality and five-year actuarial survival were compared between
      groups. There were no significant differences in the preoperative
      characteristics. Operative mortality (17% in DHCA vs. 21% in ACPB, P=0.63),
      reoperation for bleeding (20% in DHCA vs. 34% in ACPB, P=0.16) and stroke rates
      (16 DHCA vs. 24% in ACPB, P=0.33) were comparable between the two groups.
      Actuarial five-year survival rates were 74% for DHCA vs. 73% for ACPB, P=0.99. No
      significant differences in operative mortality, major morbidity and actuarial
      five-year survival were observed between DHCA and ACPB. There are some practical
      technical advantages if the distal anastomosis is performed in an open manner.
      More studies are required to determine the fate of the false lumen between the
      two techniques.

PMID- 21172940
TI  - Aortic bullet embolization revealed by peripheral ischemia after a thoracic
      gunshot wound.
AB  - We present the case of a 21-year-old male who came to the emergency ward for a
      thorax bullet wound. At our first check-up, the computed tomography (CT)-scan
      showed a pulmonary contusion, a hemothorax and a suspicious image of a thoracic
      aortic wound. The patient was stable, but soon after admission a distal ischemic
      syndrome appeared which revealed the emboli of the projectile. We removed it and
      a stent graft was implanted into the thoracic aorta. We report our experience of
      the treatment and the mechanisms that explain how such a wound did not kill the
      patient.

PMID- 21172941
TI  - Ventricular non-compaction in children: clinical characteristics and course.
AB  - Isolated left ventricular non-compaction (LVNC) is a rare cardiomyopathy
      characterized by prominent trabeculations and deep intratrabecular recesses. In
      this study, we aimed to identify the clinical characteristics of children with
      ventricular non-compaction and determine the factors affecting prognosis. We
      retrospectively evaluated 29 children with LVNC followed at Dr. Sami Ulus
      Children Hospital Pediatric Cardiology Department from December 2004 to November
      2009. There were 13 females (45%) and 16 males (55%) and the mean age at
      presentation was 4.8+/-4.6 years (one month-15 years). Although there was no
      statistical significance; early presentation age and high left ventricular end
      diastolic diameter at the diagnosis were associated with poorer prognosis.

PMID- 21172942
TI  - Right pulmonary artery agenesis and coronary-to-bronchial artery aneurysm.
AB  - Isolated unilateral pulmonary artery agenesis is a rare congenital anomaly that
      may be complicated with hemoptysis, recurrent pulmonary infections or pulmonary
      hypertension. To our knowledge the occurrence of a coronary syndrome associated
      with a coronary-to-bronchial artery saccular aneurysmal collateralization has
      never been described before. A 44-year-old female presented a congenital right
      pulmonary artery agenesis associated with a hypotrophic and multicystic right
      lung complicated with recurrent bronchitis. This patient had a coronary syndrome
      for which the coronary artery imaging showed a coronary-to-bronchial artery
      collateralization with an aneurysm at this level. It gives rise to a coronary
      syndrome by coronary steal. Two bronchial collaterals arising from a
      diaphragmatic artery and the subclavian artery were also found on the computed
      tomography (CT)-scan. This last collateral also showed another saccular aneurysm.
      We first performed an embolization of those two aneurysms in order to decrease
      the risk of hemorrhage and coronary steal, before performing a right
      pneumonectomy. In this case, the surgery was indicated because of the
      pathological lung and the risk of postembolization ischaemia. The postoperative
      course was uneventful and the patient was doing well six months later.

PMID- 21172943
TI  - HeartWare third-generation implantable continuous flow pump as biventricular
      support: mid-term follow-up.
AB  - A long-term mechanical biventricular support by HeartWare HVAS third-generation
      continuous flow pump (HeartWare, Inc, Miramar, FL, USA) was implanted in a Korean
      patient with a small chest size for treatment of a refractory end-stage heart
      failure due to an idiopathic dilative cardiomyopathy. We report our experience
      with a single patient and the early mid-term follow-up results with such a
      mechanical ventricular support.

PMID- 21172945
TI  - False aneurysm origination from the proximal anastomosis of a right ventricular
      to pulmonary artery shunt following staged repair of hypoplastic left heart
      syndrome.
AB  - The Norwood I operation, including placement of a shunt from the right ventricle
      to the pulmonary arteries, has been adopted by many surgeons for neonates with
      hypoplastic left heart syndrome. A three-year-old male who had undergone the
      Norwood I operation, and the Glenn operation, presented with a cervical pulsating
      tumor prior to the operation for total cavopulmonary connection. At the Glenn
      operation, the right ventricle to the pulmonary artery shunt was closed with a
      clip proximally, and the distal part was resected. Following the Glenn operation,
      the child had had recurrent deep sternal infections caused by Serratia
      marcescens. Cardiac catheterization showed a false aneurysm from the proximal
      shunt anastomosis. The bleeding after resternotomy was managed by initiating
      cardiopulmonary bypass via the groin vessels. Cerebral air embolies were
      prevented by systemic application of potassium, to achieve cardioplegic arrest
      during chest opening. The shunt was removed and the defect was closed. After the
      shunt was confirmed to be free from infection, a total cavopulmonary connection
      was performed after three days postoperatively. The case illustrates the
      management of retrosternal aneurysms during resternotomy in children.

PMID- 21172944
TI  - Management of acute lower limb ischemia associated with the Angio-Seal arterial
      puncture closing device.
AB  - Arterial percutaneous closure devices (APCD) could lead to severe vascular
      complications, like acute lower limb ischemia. The aim of this study was to
      evaluate retrospectively our personal series of acute lower limb ischemia
      following the use of APCD. From January 2004 to June 2009 the Angio-Seal
      percutaneous closure devices was deployed in 198 patients. Eight (4%) acute lower
      limb ischemia required urgent surgical repair. The device was removed in all
      cases. A thromboembolectomy was performed in five patients (62.5%) and in three
      (37.5%) an endarterectomy with patch closure was carried out (two saphenous vein
      and one Dacron). Limb salvage rate was 87.5%. We compared Angio-Seal
      complications group (A) with the 190 patients in which the Angio-Seal was
      successfully used without complications (group B) by means of Student's t-test.
      At 36-month follow-up with color-coded duplex ultrasounds, no chronic limb
      ischemia or other complications requiring surgical repair occurred. Diabetes,
      obesity, severe femoral atherosclerotic involvement, use of sheath size >7 Fr and
      time-consuming procedures were significant risk factors for ischemic APCD
      complications. Despite vascular injuries being uncommon after APCD deployment,
      generally a complex surgical repair is necessary. A more careful patient
      selection would be advisable.

PMID- 21172946
TI  - Factors affecting long-term satisfaction after thoracic sympathectomy for palmar
      and plantar hyperhidrosis. Is the sudomotor reflex the only villain?
AB  - The main objective of this study was to determine if there are variations in the
      level of improvement of the palmar and plantar hyperhidrotic symptoms, as well as
      the incidence and intensity of the sudomotor reflex, throughout the seasons of
      the year, after thoracic sympathectomy for hyperhidrosis. The study also looks
      for the real impact of these variables in the long-term satisfaction. A cohort of
      75 patients was followed through distinct seasons. A multivariate analysis was
      performed to identify possible variables responsible for dissatisfaction. Both
      the palmar (P=0.002) and plantar (P<0.001) symptoms and the presence and the
      intensity of the sudomotor reflex varies significantly throughout the seasons of
      the year. The sudomotor reflex was the main factor associated with low
      satisfaction in our patients in the summer (P=0.025) and winter (P<0.001) but in
      spring the lack of improvement in the hyperhidrosis in the foot was the unique
      factor related to dissatisfaction (P<0.001). The sudomotor reflex is the main
      negative factor in the summer and in the winter, independent of its intensity.
      However, at least in spring, the lack of removal of the plantar symptoms had a
      negative impact on satisfaction.

PMID- 21172947
TI  - Extracorporeal membrane oxygenation to support prolonged conventional
      cardiopulmonary resuscitation in adults with cardiac arrest from acute myocardial
      infarction at a very low-volume centre.
AB  - We aimed to analyse the outcomes of the deployment of extracorporeal membrane
      oxygenation assisted cardiopulmonary resuscitation (E-CPR) 11 times for acute
      myocardial infarction (AMI) in 10 adult patients at a very low-volume (VLV)
      centre, where perfusionists or surgeons are not always available. We conducted a
      three-year retrospective chart review. E-CPR was performed 13 times in 12 adult
      patients who had cardiac arrest events and who underwent conventional CPR for
      longer than 10 min. We excluded other aetiologies that led to E-CPR. All 11
      selected episodes of E-CPR were diagnosed as AMI. Seven patients (63.6%) were
      successfully weaned off extracorporeal membrane oxygenation (ECMO). Four patients
      survived to discharge without neurological deficits or other postE-CPR
      complications (36.3%). Seven patients died after E-CPR, and with one patient,
      there was no return of spontaneous beating during E-CPR (0.9%). Three patients
      died of unstable haemodynamics despite revascularisation of the coronary
      circulation. Three patients were successfully weaned off ECMO; however, they died
      subsequently of multiple organ dysfunction, unstable haemodynamic changes and
      septic shock from nosocomial infections, respectively. The outcome of E-CPR in
      adults with AMI was compared with previous studies at high-volume centres.
      Mortality or morbidity rates are not higher at a VLV centre.

PMID- 21172948
TI  - Open stent grafting for abdominal aortic aneurysm in a patient with a severely
      calcified abdominal aorta.
AB  - We describe a 74-year-old male who underwent open stent repair for an infrarenal
      abdominal aortic aneurysm with a severely calcified aortic neck. The stent graft
      was constructed by covering a 50-mm long Gianturco Z stent (diameter: 20 mm) with
      a Dacron prosthesis (diameter: 20 mm). The stented Dacron graft was inserted into
      the calcified aortic neck, was then sutured to the trimmed aneurysmal wall, and
      was anastomosed to a bifurcated prosthesis. The distal ends of the bifurcated
      prosthesis were anastomosed to both common femoral arteries, and the terminal
      aorta was closed. The patient had an uneventful postoperative course. This
      procedure may be a feasible and safe way to repair infrarenal abdominal aortic
      aneurysm with a severely calcified aortic neck.

PMID- 21172949
TI  - Intraoperative lung edema monitoring by microwave reflectometry.
AB  - Microwave reflectometry might be a suitable tool for the thoracic surgeon to
      monitor edema formation of the lung during lung surgery. A new setup of microwave
      reflectometry for lung water measurements was developed and tested for clinical
      application. Three lung models were used for the microwave reflectometry tests:
      1) the model of an ex vivo isolated perfused rat lung to investigate lung edema
      formation during ischemia-reperfusion (n=6), 2) the in situ lung of a human
      patient to demonstrate the feasibility of lung water monitoring during a surgical
      operation, 3) the model of an ex vivo isolated perfused human lung to investigate
      edema formation during postischemic reperfusion and to investigate the changes in
      water content in the region of a tumor. During human lung operation, significant
      changes in water content occurred in different lung areas. During isolated
      perfusion, a significant increase in lung water was measured in models 1) and 3)
      (P=0.03). Water content of tumor tissue was higher than in the surrounding
      healthy lung tissue. Microwave reflectometry offers a non-invasive approach to
      monitor lung edema formation in experimental models and during thoracic surgery.

PMID- 21172950
TI  - Inadvertent implantable cardioverter defibrillator lead placement in the left
      ventricle: long-term follow-up at nine years and management by minimally-invasive
      surgery.
AB  - We describe the case history of a 43-year-old male with type 1 Brugada syndrome.
      He was fitted with an implantable cardioverter defibrillator (ICD) for primary
      prevention nine years ago. After admission for inappropriate shocks, an abnormal
      position of the lead was discovered. Further investigations (chest X-ray and
      transesophageal echocardiography) showed that the ICD lead was in fact in the
      left ventricle. The ICD lead was removed successfully using video-assisted
      thoracoscopic surgery.

PMID- 21172951
TI  - Slow-release of methanogenic inhibitors derived from encapsulated calcium carbide
      using paraffin wax and/or rosin: matrix optimization and diffusion
      characteristics.
AB  - Acetylene has been found to significantly inhibit biological activity of
      methanogens and thus might be applicable for reducing the generation and emission
      of methane from municipal solid waste landfills. However, acetylene is gaseous
      and so it is considered physically infeasible to directly apply this gas to waste
      in landfill conditions. In the present study, a novel acetylene release mechanism
      was tested, using a matrix of acetylene entrapped in high hydrophobic paraffin
      wax and/or rosin and calcium carbide capsules with a ratio of 1.0 g g(-1) matrix
      and a diameter of 10 mm to facilitate the gradual release of acetylene. A
      diffusion mechanism model (Q = &b.gamma; * t (0.5)) for the matrix was derived
      based on the T. Higuchi equation, and the effective diffusion coefficients (D(e))
      were acquired by linear fitting. Additionally, it was found that D(e) remained
      constant when the rosin content was up to more than 20% g g(-1) matrix.

PMID- 21172952
TI  - BI 44370 TA, an oral CGRP antagonist for the treatment of acute migraine attacks:
      results from a phase II study.
AB  - METHODS: Four hundred and sixty-one adult subjects with migraine were randomised
      to one of five treatments, the oral antagonist at the calcitonin gene-related
      peptide (CGRP) receptor BI 44370 TA (50 mg, 200 mg, 400 mg), active comparator
      eletriptan 40 mg or placebo. The analysis included 341 subjects who took study
      medication. RESULTS: The primary endpoint, pain-free after two hours, was reached
      by significantly more subjects in the BI 44370 TA 400 mg (20/73 = 27.4%) and
      eletriptan 40 mg (24/69 = 34.8%) groups compared to placebo (6/70 = 8.6%, p =
      .0016), but not by subjects in the BI 44370 TA 200 mg group (14/65 = 21.5%). The
      effect of 50 mg BI 44370 TA (5/64 = 7.8%) was similar to that of placebo.
      Analysis of secondary endpoints supported the conclusion from the primary
      analysis. The frequency of adverse events was low in all groups. CONCLUSION:
      Efficacy of BI 44370 TA was shown in a dose-dependent manner in the treatment of
      acute migraine attacks.

PMID- 21172953
TI  - Multimodal neuroimaging in a child with sporadic hemiplegic migraine: a
      contribution to understanding pathogenesis.
AB  - BACKGROUND: Hemiplegic migraine (HM) is a rare variety of migraine with aura,
      characterized by motor deficits during the aura, often beginning in childhood.
      The hemiplegic attacks can be severe and prolonged but the prognosis is usually
      good. Data on neuroimaging, including diffusion-weighted imaging (DWI) and
      spectroscopy, during prolonged attacks of HM are quite limited, particularly in
      children. CASE: An eight-year-old female had a prolonged attack of sporadic HM
      characterized by right-sided hemiplegia, global aphasia, fever and impairment of
      consciousness. MRI nine hours after hemiplegia onset was negative, while the
      following MRI scans (days 4 and 11) documented a progressive increase in cortical
      swelling in the left hemisphere with mild hyperintensity on DWI and mild
      reduction of apparent diffusion coefficient values. Proton MRI spectroscopy (MRS)
      (day 15) showed a decrease in the N-acetylaspartate/creatine ratio in the left
      hemisphere. (99m)Tc-ECD single-photon emission tomography (SPET) (day 27) showed
      marked left hemispheric hypoperfusion. The patient recovered completely after 40
      days and neuroimaging follow-up (MRI and SPET) after six months was normal. The
      patient carried a missense mutation of the ATP1A2 gene. CONCLUSION: Multimodal
      neuroimaging (MRI, DWI, MRS, SPET) in a prolonged HM attack supports evidence for
      a primary neuronal dysfunction.

PMID- 21172954
TI  - Roles of old players in the suppression of a new player: networks for the
      transcriptional control of angiogenesis.
AB  - During the formation of blood vessels, Id1, a member of the helix-loop-helix
      (HLH) family, and TAL1/SCL, a basic HLH (bHLH) transcription factor, play
      important roles in the activation of endothelial cells. Recent reports revealed
      that E2-2, another bHLH transcription factor, inhibits angiogenesis in vitro and
      in vivo by suppressing the expression of vascular endothelial growth factor
      receptor 2 (VEGFR2). Id1 and TAL1/SCL dimerize with E2-2 and relieve the E2-2
      mediated down-regulation of VEGFR2 expression, leading to the activation of
      endothelial cells. These findings reveal a novel interplay between HLH
      transcription factors that regulate angiogenesis.

PMID- 21172955
TI  - UV radiation-responsive proteins in rice leaves: a proteomic analysis.
AB  - Depletion of stratospheric ozone has led to increased UV radiation reaching the
      surface of the Earth. This may damage plants. Using physiological, proteomic and
      quantitative real-time PCR (qPCR) methods, we systematically studied the response
      of 16-day-old rice seedlings to UV [0.67 W m(-2) biologically effective UVB
      (UVB(BE)) and 0.28 W m(-2) UVA] exposure for 6, 12 and 24 h. UV exposure resulted
      in the appearance of light brown patches on leaves, a decrease in the net
      photosynthetic rate (Pn), lipid peroxidation, accumulation of UV-absorbing
      compounds (including flavonoids and other phenolic pigments) and differential
      expression of 22 proteins. Both physiological and molecular responses became
      stronger with increasing UV exposure time, indicating the effects of UV
      accumulation on plants. UV-induced responses included (i) phytohormone-regulative
      responses (up-regulation of proteins related to phytohormone synthesis such as
      IAA and ethylene); (ii) injurious responses (photosynthesis suppression, lipid
      peroxidation and visible injury); and (iii) protective responses (accumulation of
      UV-absorbing compounds and differential expression of proteins involved in
      detoxification/antioxidation, defense, protein processing, RNA processing,
      carbohydrate metabolism and secondary metabolism). The identification of UV
      responsive proteins provided a better understanding of the molecular mechanism of
      plant responses to UV stress. Proteomic and qPCR analysis identified one up
      regulated and two induced proteins with important functions: tryptophan synthase
      alpha chain (production of radical oxygen species), glyoxalase I
      (detoxification/antioxidation) and a Bet v I family protein (defense). These
      results will contribute to future research into their roles in UV stress
      responses in plants.

PMID- 21172956
TI  - CT characteristics of a uterus-like mass in the sigmoid mesocolon.
AB  - A uterus-like mass is a rare, benign extra-uterine tumour composed of smooth
      muscle and endometrium. The majority of uterus-like masses occur in the ovary.
      Rarely, uterus-like masses occur in the broad ligament, small bowel, small bowel
      mesentery or uterine cervix. Here, we report a case of a uterus-like mass in the
      sigmoid mesocolon. A well-defined, markedly enhanced soft-tissue mass with
      central cystic change and haemorrhage was observed on CT. The current report
      describes the CT characteristics of this sigmoid mesocolon uterus-like mass
      together with the differential diagnoses.

PMID- 21172957
TI  - Littoral cell angioma in a splenunculus: a case report.
AB  - Littoral cell angioma (LCA) is a rare primary splenic vascular tumour that arises
      from the littoral cells that line the red pulp sinuses. It is usually
      asymptomatic and is discovered incidentally on imaging for other pathologies.
      Radiologists should be aware of these lesions as they may be mistaken for
      malignant lesions and lead to unnecessary surgery. We present a case of LCA
      recurrence within a splenunculus that was discovered incidentally in a 60-year
      old patient being investigated for right upper quadrant pain.

PMID- 21172958
TI  - Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: an unusual cause of
      cyclical ectopic adrenocorticotrophic syndrome.
AB  - We present the case of a 73-year-old woman who presented with clinical features
      of Cushing's syndrome, confirmed biochemically with elevated levels of cortisol
      and adrenocorticotrophic hormone (ACTH). Petrosal venous sampling showed no ACTH
      gradient and MRI of pituitary was normal, suggesting ectopic ACTH production. In
      the course of further investigations, a thoracic CT was carried out to look for
      evidence of bronchial neoplasm. Although there was no discrete tumour identified,
      CT revealed widespread fine nodularity in the right middle and lower lobe.
      Subsequent trans-bronchial and video-assisted thorascopic biopsy showed pulmonary
      tumourlets and two typical carcinoid tumours on a background of diffuse
      idiopathic pulmonary neuroendocrine cell neoplasia (DIPNECH). We describe the
      clinical, radiological and histological features of this rare condition.

PMID- 21172959
TI  - Magnetic resonance cholangiopancreatography diagnosis of choledochal cyst
      involving the cystic duct: report of three cases.
AB  - Here we describe three cases of choledochal cyst involving the cystic duct or
      isolated dilatation of the cystic duct. All cases were visualised on MR
      cholangiopancreatography (MRCP) imaging. We report findings of ultrasonography,
      CT and MRCP. These cases are extremely rare; nine cases have been reported in the
      English-language literature. This anomaly was not included in Todani's
      classifications of choledochal cysts, a system that is accepted worldwide. We
      think that this variant anomaly will be included in this classification system in
      the near future.

PMID- 21172960
TI  - Localised right upper-lobe pulmonary oedema caused by extension of giant cell
      carcinoma to the mitral valve.
AB  - Giant cell carcinoma of the lung is a very rare primary malignant tumour and
      localised right upper-lobe pulmonary oedema is also unusual. We report a case of
      giant cell carcinoma, which invaded the left atrium through the left pulmonary
      vein and caused localised right upper-lobe pulmonary oedema.

PMID- 21172961
TI  - The role of somatostatin analogues in the treatment of advanced malignant
      thymomas: case report and review of the literature.
AB  - Thymomas are the most common tumours of the anterior mediastinum; their clinical
      course is often complicated by accompanying autoimmune and paraneoplastic
      syndromes. Advanced malignant thymoma is particularly challenging to manage owing
      to the lack of evidence from randomised trials to guide treatment. Combination
      first-line chemotherapy has been trialled in several small studies and has been
      reported to produce a 50-80% response with platinum-containing regimes.
      Progression following first-line chemotherapy is difficult to manage as most of
      these patients maintain a good performance status and demand further active
      palliative treatment. There is no standard second-line treatment. We report a
      good clinical and radiological response to third-line palliative octreotide
      therapy in a patient who had a positive octreotide scan.

PMID- 21172963
TI  - The launch of the first UK charity devoted to radiotherapy: ACORRN -- Action
      Radiotherapy.
AB  - The Academic Clinical Oncology and Radiobiology Research Network (ACORRN) was set
      up to support research and development in radiotherapy in the UK. This innovative
      networking initiative was launched initially by the National Cancer Research
      Institute in 2005 to harness the power of the radiation research base in the UK.
      Through an interactive website a co-ordinated network of multidisciplinary
      radiation researchers has been established. The network has developed to a stage
      where it can be self-funding and dedicated to improving radiotherapy for cancer.
      A patient interactive section and extended support for service development will
      ensure that anyone treated in the UK will have immediate access to the best
      knowledge in the country. This provides a solution for cost-effectiveness and
      future improvement of cancer care and is seen as a new model to support
      healthcare development and delivery. The charity ACORRN - Action Radiotherapy
      aims to support radiotherapy research and development and was launched in the
      House of Lords in July 2010.

PMID- 21172964
TI  - The corpus callosum: white matter or terra incognita.
AB  - The corpus callosum is the largest white matter structure in the brain,
      consisting of 200-250 million contralateral axonal projections and the major
      commissural pathway connecting the hemispheres of the human brain. The pathology
      of the corpus callosum includes a wide variety of entities that arise from
      different causes such as congenital, inflammatory, tumoural, degenerative,
      infectious, metabolic, traumatic, vascular and toxic agents. The corpus callosum,
      or a specific part of it, can be affected selectively. Numerous pathologies of
      the corpus callosum are encountered during CT and MRI. The aim of this study is
      to facilitate a better understanding and thus treatment of the pathological
      entities of the corpus callosum by categorising them according to their causes
      and their manifestations in MR and CT imaging. Familiarity with its anatomy and
      pathology is important to the radiologist in order to recognise its disease at an
      early stage and help the clinician establish the optimal therapeutic approach.

PMID- 21172965
TI  - Diffusion-weighted magnetic resonance imaging for monitoring prostate cancer
      progression in patients managed by active surveillance.
AB  - OBJECTIVES: We studied patients managed by active surveillance to determine
      whether there was a difference over time in apparent diffusion coefficients
      (ADCs) derived from diffusion-weighted MRI in those who progressed to radical
      treatment (progressors, n = 17) compared with those who did not (non-progressors,
      n = 33). METHODS: 50 consecutive patients (Stage T1/2a, Gleason grade <= 3+4,
      prostate-specific antigen (PSA) <15 ng ml-1, <50% cores positive) were imaged
      endorectally (baseline and 1-3 years follow-up) with T2 weighted (T2W) and echo
      planar diffusion-weighted MRI sequences. Regions of interest drawn on ADC maps
      with reference to the T2W images yielded ADC(all) (b = 0-800), ADC(fast) (b = 0
      300) and ADC(slow) (b = 300-800) for whole prostate (minus tumour) and tumour
      (low signal-intensity peripheral zone lesion in biopsy-positive octant). RESULTS:
      Tumour and whole prostate ADC(all) and ADC(fast) were significantly reduced over
      time in progressors (p = 0.03 and 0.03 for tumours, respectively; p = 0.02 and
      0.007 for the whole prostate, respectively). There were no significant changes in
      ADC over time in non-progressors. A 10% reduction in tumour ADC(all) indicated
      progression with a 93% sensitivity and 40% specificity (A(z) of receiver
      operating characteristic (ROC) curve = 0.68). Percentage reductions in whole
      prostate ADC(all), ADC(fast) and ADC(slow) were also significantly greater in
      progressors than in non-progressors (p = 0.01, 0.03 and 0.008, respectively).
      CONCLUSION: This pilot study shows that DW-MRI has potential for monitoring
      patients with early prostate cancer who opt for active surveillance.

PMID- 21172966
TI  - Dose and image quality comparison between prospectively gated axial and
      retrospectively gated helical coronary CT angiography.
AB  - OBJECTIVE: Our aim was to compare image quality, coronary segment assessability
      and radiation dose in prospectively gated axial (PGA) coronary CT angiography
      (CTA) and conventional retrospectively gated helical (RGH) coronary CTA. METHODS:
      Institutional review committee approval and informed consent were obtained. RGH
      CTA was performed in 41 consecutive patients (33 males, 8 females; mean age 52.6
      years), then the PGA CTA technique was evaluated in 41 additional patients (24
      males, 17 females; mean age 57.3 years) all with a pre-scan heart rate of <=70
      beats per minute (bpm). Two radiologists, blinded to clinical information,
      independently scored subjective image quality on a five-point ordinal scale.
      RESULTS: The mean effective dose in the PGA group was 4.7+/-0.9 mSv, representing
      a 69% dose reduction compared with the RGH CTA group (15.1+/-1.9 mSv, p<0.001).
      The mean segmental image quality score was significantly higher in the PGA group
      (3.4 vs 3.2) than in the RGH CTA group (p<0.005). The percentage of assessable
      segments was 98.1% in the PGA group and 97.3% in the RGH group (p = 0.610).
      CONCLUSION: PGA CTA offers a significant reduction in radiation dose compared
      with RGH CTA, with comparable image quality for patients with heart rates below
      70 bpm.

PMID- 21172967
TI  - Occupational radiation doses to the extremities and the eyes in interventional
      radiology and cardiology procedures.
AB  - OBJECTIVES: The aim of this study was to determine occupational dose levels in
      interventional radiology and cardiology procedures. METHODS: The study covered a
      sample of 25 procedures and monitored occupational dose for all laboratory
      personnel. Each individual wore eight thermoluminescent dosemeters next to the
      eyes, wrists, fingers and legs during each procedure. Radiation protection
      shields used in each procedure were recorded. RESULTS: The highest doses per
      procedure were recorded for interventionists at the left wrist (average 485 MUSv,
      maximum 5239 MUSv) and left finger (average 324 MUSv, maximum 2877 MUSv), whereas
      lower doses were recorded for the legs (average 124 MUSv, maximum 1959 MUSv) and
      the eyes (average 64 MUSv, maximum 1129 MUSv). Doses to the assisting nurses
      during the intervention were considerably lower; the highest doses were recorded
      at the wrists (average 26 MUSv, maximum 41 MUSv) and legs (average 18 MUSv,
      maximum 22 MUSv), whereas doses to the eyes were minimal (average 4 MUSv, maximum
      16 MUSv). Occupational doses normalised to kerma area product (KAP) ranged from
      11.9 to 117.3 MUSv/1000 cGy cm2 and KAP was poorly correlated to the
      interventionists' extremity doses. CONCLUSION: Calculation of the dose burden for
      interventionists considering the actual number of procedures performed annually
      revealed that dose limits for the extremities and the lenses of the eyes were not
      exceeded. However, there are cases in which high doses have been recorded and
      this can lead to exceeding the dose limits when bad practices are followed and
      the radiation protection tools are not properly used.

PMID- 21172968
TI  - Voxel-based diffusion tensor imaging detects pyramidal tract degeneration in
      primary lateral sclerosis.
AB  - OBJECTIVE: Primary lateral sclerosis (PLS) is a progressive degenerative disorder
      affecting upper motor neurons and requires a clinical diagnosis. Diffusion tensor
      imaging (DTI) is a quantitative method for assessing white matter fibre
      integrity. The purpose of the study was to evaluate the involvement of upper
      motor neurons by using DTI in PLS. METHODS: A patient with PLS was compared with
      eight age-matched controls. Differences in fractional anisotropy (FA) index were
      assessed using DTI on a voxel-by-voxel basis. RESULTS: Decreased FA was observed
      in the proximal part of the pyramidal tract bilaterally, which indicated
      degeneration of the pyramidal cells. CONCLUSION: Voxel-based DTI could be used as
      an objective marker for detecting upper motor neuron degeneration in PLS.

PMID- 21172969
TI  - Clinical presentations and imaging findings of neuroblastoma beyond abdominal
      mass and a review of imaging algorithm.
AB  - Neuroblastoma is one of the most common malignant neoplasms in childhood. The
      most common clinical presentation of this tumour is abdominal mass. However,
      affected children may have various clinical presentations as a result of
      disseminated metastatic disease or associated paraneoplastic syndromes at the
      time of diagnosis. In this article we have outlined the imaging findings in seven
      patients with "extra-abdominal" presentation of neuroblastoma and the pitfalls in
      making the correct diagnosis. The purpose of this pictorial review is to alert
      the general radiologist to the possible presentations of this common childhood
      malignancy to derive early detection and diagnosis.

PMID- 21172970
TI  - A case of chronic knee pain and swelling.

PMID- 21172972
TI  - Metabolic profiles in serum of mouse after chronic exposure to drinking water.
AB  - The toxicity of Nanjing drinking water on mouse (Mus musculus) was detected by
      (1)H nuclear magnetic resonance (NMR)-based metabonomic method. Three groups of
      mice were fed with drinking water (produced by Nanjing BHK Water Plant), 3.8
      MUg/L benzo(a)pyrene as contrast, and clean water as control, respectively, for
      90 days. It was observed that the levels of lactate, alanine, and creatinine in
      the mice fed with drinking water were increased and that of valine was decreased.
      The mice of drinking water group were successfully separated from control. The
      total concentrations of polycyclic aromatic hydrocarbons (PAHs), phthalates
      (PAEs), and other organic pollutants in the drinking water were 0.23 MUg/L, 4.57
      MUg/L, and 0.34 MUg/L, respectively. In this study, Nanjing drinking water was
      found to induce distinct perturbations of metabolic profiles on mouse including
      disorders of glucose-alanine cycle, branched-chain amino acid and energy
      metabolism, and dysfunction of kidney. This study suggests that metabonomic
      method is feasible and sensitive to evaluate potential toxic effects of drinking
      water.

PMID- 21172974
TI  - Six Kosovar doctors face charges of illegal organ trafficking.

PMID- 21172973
TI  - Protective effects of selenium on methimazole-induced anemia and oxidative stress
      in adult rats and their offspring.
AB  - The present study investigates the potential ability of selenium, considered as
      an antioxidant with pharmacological property to alleviate oxidative stress and
      hematological parameter disorders induced by methimazole, an antithyroid drug.
      Pregnant Wistar rats were randomly divided into four groups of six each: group I
      served as negative control and received a standard diet; group II received 250
      mg/L of methimazole in drinking water and a standard diet; group III received
      both methimazole (250 mg/L, orally) and selenium (0.5 mg/kg of diet) supplemented
      to the standard diet; group IV served as positive control and received a
      supplement of selenium in the diet (0.5 mg/kg of diet) as sodium selenite
      (Na(2)SeO(3)). Treatment was started from the 14th day of pregnancy until day 14
      after delivery. Methimazole reduced the number of red blood cells, hemoglobin
      concentration and hematocrit in mothers and their pups. Besides, plasma iron,
      vitamins B(9), B(12), C and E levels were reduced. Lipid peroxidation increased,
      objectified by high malondialdehyde levels and lactate dehydrogenase activity in
      plasma, while glutathione, glutathione peroxidase, superoxide dismutase and
      catalase activities showed a significant decline. Co-administration of selenium
      through diet improved all the parameters cited above. It can be concluded that
      the administration of selenium alleviates methimazole-induced toxicity, thus
      demonstrating its antioxidant efficacy.

PMID- 21172976
TI  - Companies that want to charge a higher than basic price for a new drug will have
      to give evidence that it's worth it.

PMID- 21172977
TI  - Ways to control alcohol price.

PMID- 21172978
TI  - Reducing insulin errors. Try electronic prescribing.

PMID- 21172979
TI  - Knife crime victims. Disclosing identity is not sensible or effective.

PMID- 21172980
TI  - Abandoned HealthSpace. Sharing access might increase engagement.

PMID- 21172981
TI  - It's a great idea and workable.

PMID- 21172982
TI  - Abandoned HealthSpace. Smart phones may help.

PMID- 21172983
TI  - Patient's view of HealthSpace.

PMID- 21172984
TI  - Go now, says NHS chief. Bad soldiers and bad officers.

PMID- 21172985
TI  - Go now, says NHS chief. Time for debate.

PMID- 21172986
TI  - BAPO response to Des Spence.

PMID- 21172987
TI  - Public health advances. Concerns about tobacco control.

PMID- 21172988
TI  - Paediatric ENT surgery. Evidence above vitriol.

PMID- 21172990
TI  - Dyspnea-related anxiety: The Dutch version of the Breathlessness Beliefs
      Questionnaire.
AB  - Dyspnea-related anxiety may lead to reduced quality of life and functional
      disability through fearful avoidance of dyspnea-evoking activity. We describe the
      validation of a generic - diagnosis-independent - instrument assessing dyspnea
      related anxiety. A total of 187 patients with respiratory diseases completed the
      Breathlessness Beliefs Questionnaire (BBQ), a 17-item questionnaire adapted from
      the Tampa Scale for Kinesiophobia (TSK), a measure of how harmful pain patients
      think painful movement is and to what extent they think activity should be
      avoided. Measures of negative and positive affectivity (PANAS), anxiety and
      depression (HADS), functional status (PFSDQ), and health-related quality of life
      (CRDQ) were also completed. Principal component analysis and item-total
      correlations suggested a reliable (reduced) 11-item BBQ (Cronbach's alpha = .85)
      with two factors converging with the TSK factors: a 'somatic focus' factor
      assessing the harmfulness of dyspnea and the underlying pathology and an
      'activity avoidance' factor assessing beliefs that activity should be avoided.
      Correlational analyses support the construct validity of the BBQ: higher scores
      on the BBQ are associated with reduced health-related quality of life and
      functional status. Associations between 'somatic focus' and negative affectivity
      and anxiety and between 'activity avoidance' and positive affectivity and
      depression further supported the validity of the BBQ and its subscales. The BBQ
      is a valid, short, and useful instrument to assess respiratory patients' beliefs
      about the harmfulness of their disease and physical activities. Further research
      is needed to document to what extent BBQ scores are related to daily life
      activities and symptoms.

PMID- 21172991
TI  - Pandemic H1N1 in children requiring intensive care in Australia and New Zealand
      during winter 2009.
AB  - OBJECTIVE: To describe in detail the pediatric intensive care experience of
      influenza A, particularly pandemic H1N1-09, in Australia and New Zealand during
      the 2009 Southern Hemisphere winter and to compare the pediatric experience with
      that of adults. METHOD: This was an inception-cohort study of all children who
      were admitted to intensive care with confirmed influenza A during winter 2009 at
      all general ICUs and PICUs in Australia and New Zealand. RESULTS: From June 1
      through August 31, 2009, 107 children (20.0 per million [95% confidence interval:
      16.1-23.8]) with influenza A, including 83 (15.5 per million [95% confidence
      interval: 12.1-18.9]) with H1N1-09 were admitted to ICUs. Fifty-two percent (39
      of 75) of children with H1N1-09 had 1 or more comorbidity, most commonly
      neurologic (20%). Most (48 of 83 [58%]) presented with pneumonia. Thirteen of 83
      (16%) had neurologic presentations. Eighty percent of the children with H1N1-09
      required ventilation. Mortality was lower than in adults: 6 of 83 (7%) vs 114 of
      668 (17%) (P = .02). The median length of stay for children with H1N1-09 was 5
      days. Children with H1N1-09 occupied 773 bed-days (147 per million children) and
      5.8% of specialist PICU beds. Presentation with septic shock or after cardiac
      arrest and the presence of 1 or more comorbidities were risk factors for severe
      disease. CONCLUSIONS: H1N1-09 caused a substantial burden on pediatric intensive
      care services in Australia and New Zealand. Compared with adults, children more
      commonly had nonrespiratory presentations and required ventilation more often but
      had a lower mortality rate.

PMID- 21172992
TI  - Geographic maldistribution of primary care for children.
AB  - OBJECTIVES: This study examines growth in the primary care physician workforce
      for children and examines the geographic distribution of the workforce. METHODS:
      National data were used to calculate the local per-capita supply of clinically
      active general pediatricians and family physicians, measured at the level of
      primary care service areas. RESULTS: Between 1996 and 2006, the general
      pediatrician and family physician workforces expanded by 51% and 35%,
      respectively, whereas the child population increased by only 9%. The 2006 per
      capita supply varied by >600% across local primary care markets. Nearly 15
      million children (20% of the US child population) lived in local markets with
      <710 children per child physician (average of 141 child physicians per 100 000
      children), whereas another 15 million lived in areas with >4400 children per
      child physician (average of 22 child physicians per 100 000 children). In
      addition, almost 1 million children lived in areas with no local child physician.
      Nearly all 50 states had evidence of similar extremes of physician
      maldistribution. CONCLUSIONS: Undirected growth of the aggregate child physician
      workforce has resulted in profound maldistribution of physician resources.
      Accountability for public funding of physician training should include efforts to
      develop, to use, and to evaluate policies aimed at reducing disparities in
      geographic access to primary care physicians for children.

PMID- 21172993
TI  - Breastfeeding duration and academic achievement at 10 years.
AB  - INTRODUCTION: The aim of this study was to examine the relationship between
      duration of breastfeeding and educational outcomes. We hypothesized that longer
      periods of breastfeeding would predict better educational outcomes in middle
      childhood. METHODS: The Western Australian Pregnancy Cohort (Raine) Study used a
      cohort of 2900 women who were enrolled at 18 weeks' gestation; with 2868 live
      born children were followed prospectively. At ~10 years of age, data from 1038
      children were linked to standardized mathematics, reading, writing, and spelling
      scores. Associations between breastfeeding duration and educational outcomes were
      estimated by using linear models with adjustment for gender, family income,
      maternal factors, and early stimulation at home through reading. RESULTS: Ten
      year-old children who were predominantly breastfed for 6 months or longer in
      infancy had higher academic scores than children who were breastfed for less than
      6 months. The effect of breastfeeding on educational outcomes differed according
      to gender; boys were particularly responsive (in mathematics, spelling, reading,
      and writing) to a longer duration of breastfeeding. CONCLUSIONS: Predominant
      breastfeeding for 6 months or longer was positively associated with academic
      achievement in children at 10 years of age. However, the effectiveness of
      breastfeeding differed according to gender; the benefits were only evident for
      boys.

PMID- 21172994
TI  - Bone marrow donation between siblings living in different families.

PMID- 21172995
TI  - Diarrhea-associated hospitalizations among US children over 2 rotavirus seasons
      after vaccine introduction.
AB  - OBJECTIVE: After implementation of rotavirus vaccination in 2006, large decreases
      in rates of severe diarrhea among US children occurred in 2007-2008. We
      ascertained whether these decreases were sustained in 2008-2009. METHODS: We
      examined hospital discharge data from a national network of pediatric hospitals
      and compared all-cause diarrhea-related and rotavirus-specific hospitalizations
      in 3 prevaccine rotavirus seasons (2003-2006) with those in 2 postvaccine seasons
      (2007-2008 and 2008-2009) among children <5 years of age. We defined rotavirus
      seasons using data from a national laboratory surveillance network. RESULTS: At
      62 consistently reporting hospitals, a median of 15 645 diarrhea-related
      hospitalizations (range: 14 881-16 884 hospitalizations) occurred each rotavirus
      season among children <5 years of age in 2003-2006. Compared with this median,
      all-cause diarrhea-related hospitalizations decreased by 50% (n = 7760) in 2007
      2008 and by 29% (n = 11 039) in 2008-2009. In 2007-2008, reductions of 47% to 55%
      were seen for all age groups, including vaccine-ineligible children >=2 years of
      age (48%). In 2008-2009, these reductions decreased in magnitude, especially
      among children >=2 years of age (17%). Decreases in 2007-2008 and 2008-2009 were
      similar in the Northeast and West, but decreases were smaller in 2008-2009,
      compared with 2007-2008, in the Midwest and South. CONCLUSIONS: Compared with
      prevaccine seasons, decreases in diarrhea- and rotavirus-associated
      hospitalizations seen in 2007-2008 were sustained in 2008-2009 but were somewhat
      smaller. Given the variability in diarrhea-related hospitalization trends over
      the 2 postvaccine seasons according to age group and region, continued
      surveillance is required for full assessment of the impact of rotavirus
      vaccination.

PMID- 21172996
TI  - Contrasting parents' and pediatricians' perspectives on shared decision-making in
      ADHD.
AB  - OBJECTIVE: The goal was to compare how parents and clinicians understand shared
      decision-making (SDM) in attention-deficit/hyperactivity disorder (ADHD), a
      prototype for SDM in pediatrics. METHODS: We conducted semi-structured interviews
      with 60 parents of children 6 to 12 years of age with ADHD (50% black and 43%
      college educated) and 30 primary care clinicians with varying experience. Open
      ended interviews explored how pediatric clinicians and parents understood SDM in
      ADHD. Interviews were taped, transcribed, and then coded. Data were analyzed by
      using a modified grounded theory approach. RESULTS: Parents and clinicians both
      viewed SDM favorably. However, parents described SDM as a partnership between
      equals, with physicians providing medical expertise and the family contributing
      in-depth knowledge of the child. In contrast, clinicians understood SDM as a
      means to encourage families to accept clinicians' preferred treatment. These
      findings affected care because parents mistrusted clinicians whose presentation
      they perceived as biased. Both groups discussed how real-world barriers limit the
      consideration of evidence-based options, and they emphasized the importance of
      engaging professionals, family members, and/or friends in SDM. Although primary
      themes did not differ according to race, white parents more commonly received
      support from medical professionals in their social networks. CONCLUSIONS: Despite
      national guidelines prioritizing SDM in ADHD, challenges to implementing the
      process persist. Results suggest that, to support SDM in ADHD, modifications are
      needed at the practice and policy levels, including clinician training,
      incorporation of decision aids and improved strategies to facilitate
      communication, and efforts to ensure that evidence-based treatment is accessible.

PMID- 21172998
TI  - Testosterone levels in umbilical-cord blood and risk of pyloric stenosis.
AB  - OBJECTIVE: The risk of infantile hypertrophk pylonc stenosis is ~5 times more
      common in male than female infants. It has been hypothesized that the higher risk
      among male infants is associated with high levels of testosterone causing
      hypertrophy of the pylorus muscle. To test this hypothesis, we examined the
      association between the testosterone levels in the umbilical-cord blood and the
      risk of infantile hypertrophic pyloric stenosis. PATIENTS AND METHODS: We
      conducted a matched case-control study nested in the Danish National Birth Cohort
      using risk-set sampling. From a cohort of 101 042 pregnancies, we identified
      umbilical-cord blood samples from 46 case subjects (43 male and 3 female infants)
      who developed infantile hypertrophic pyloric stenosis in the first year of life
      and 150 gender- and gestational age-matched control subjects. The testosterone
      levels were measured by liquid chromatography-tandem mass spectrometry. Rate
      ratios were estimated by using conditional logistic regression. RESULTS: In male
      infants, the mean testosterone level at birth was 0.78 nmol/L in case subjects
      and 0.91 nmol/L in control subjects. The rate of infantile hypertrophic pyloric
      stenosis was inversely, albeit insignificantly, associated with the testosterone
      levels in male infants; there was a 29% (95% confidence interval: -46% to 65%; P
      = 35) lower rate per nmol/L. The association was not modified according to age,
      gestational age, or birth order. CONCLUSIONS: We found no support for the
      hypothesis that high testosterone levels in the umbilical-cord blood are strongly
      associated with a subsequently higher risk for infantile hypertrophic pyloric
      stenosis in male infants.

PMID- 21172997
TI  - Effect of defibrillation energy dose during in-hospital pediatric cardiac arrest.
AB  - OBJECTIVE: To examine the effectiveness of initial defibrillation attempts. We
      hypothesized that (1) an initial shock dose of 2 +/- 10 J/kg would be less
      effective for terminating fibrillation than suggested in published historical
      data and (2) a 4 J/kg shock dose would be more effective. PATIENTS AND METHODS:
      This was a National Registry of Cardiopulmonary Resuscitation prospective,
      multisite, observational study of in-hospital pediatric (aged <=18 years)
      ventricular fibrillation or pulseless ventricular tachycardia cardiac arrests
      from 2000-2008. Termination of ventricular fibrillation or pulseless ventricular
      tachycardia and event survival after initial shocks of 2 J/kg were compared with
      historic controls and a 4 J/kg shock dose. RESULTS: Of 266 children with 285
      events, 173 of 285 (61%) survived the event and 61 of 266 (23%) survived to
      discharge. Termination of fibrillation after initial shock was achieved for 152
      of 285 (53%) events. Termination of fibrillation with 2 +/- 10 J/kg was much less
      frequent than that seen among historic control subjects (56% vs 91%; P < .001),
      but not different than 4 J/kg. Compared with 2 J/kg, an initial shock dose of 4
      J/kg was associated with lower rates of return of spontaneous circulation (odds
      ratio: 0.41 [95% confidence interval: 0.21-0.81]) and event survival (odds ratio:
      0.42 [95% confidence interval: 0.18-0.98]). CONCLUSIONS: The currently
      recommended 2 J/kg initial shock dose for in-hospital cardiac arrest was
      substantially less effective than previously published. A higher initial shock
      dose (4 J/kg) was not associated with superior termination of ventricular
      fibrillation or pulseless ventricular tachycardia or improved survival rates. The
      optimal pediatric defibrillation dose remains unknown.

PMID- 21172999
TI  - Earliest appropriate time for administering neurobehavioral assessment in newborn
      infants.
AB  - OBJECTIVE: To assess the effect of examination time on newborn neurobehavioral
      examinations administered within 48 hours of delivery and to identify the
      earliest appropriate time for performing the assessment. METHODS: We analyzed
      data from neurobehavioral examinations on 324 newborns using the NICU Network
      Neurobehavioral Scale (NNNS). Trends over examination time and cumulative
      percentage within published normal ranges were analyzed to identify the earliest
      appropriate time for administering the examination. Ordinal logistic regression
      and multivariate regression were used for testing and defining the earliest
      appropriate time for administering the examination without being influenced by
      acute effects of labor and delivery while controlling for several potential
      confounding factors. RESULTS: The arousal, excitability, lethargy, quality-of
      movement, hypotonicity, and nonoptimal-reflexes scales were sensitive to timing
      of the examination. Results of ordinal logistic regression showed that 20 hours
      after delivery seemed to be the earliest appropriate time for administering
      newborn NNNS examinations. The proportion of NNNS scores within the normal range
      increased with time significantly when the examination was made less than 20
      hours after delivery (n = 148) (odds ratio: 1.12 [95% confidence interval: 1.02
      1.23]), but there was no longer significant association with time of examination
      after 20 hours (n = 176) (odds ratio: 1.04 [95% confidence interval: 0.99-1.09]).
      This result was confirmed by multivariate regression. CONCLUSIONS: We recommend
      20 hours after delivery as the earliest appropriate time for administering
      newborn NNNS examinations to obtain results reflecting outcomes that are a
      representative assessment of newborn neurobehavior and not contaminated by acute
      effects of labor and delivery.

PMID- 21173001
TI  - Annual summary of vital statistics: 2008.
AB  - The number of births in the United States decreased between 2007 and 2008
      (preliminary estimate: 4 251 095). Birth rates declined among all women aged 15
      to 39 years; the decrease among teenagers reverses the increases seen in the
      previous 2 years. The total fertility rate decreased 2% in 2008 to 2085.5 births
      per 1000 women. The proportion of all births to unmarried women increased to
      40.6% in 2008, up from 39.7% in 2007. The 2008 preterm birth rate was 12.3%, a
      decline of 3% from 2007. In 2008, 32.3% of all births occurred by cesarean
      delivery, up nearly 2% from 2007. Twin and triplet birth rates were unchanged.
      The infant mortality rate was 6.59 infant deaths per 1000 live births in 2008
      (significantly lower than the rate of 6.75 in 2007). Life expectancy at birth was
      77.8 years in 2008. Crude death rates for children aged 1 to 19 years decreased
      by 5.5% between 2007 and 2008. Unintentional injuries and homicide were,
      respectively, the first and second leading causes of death in this age group.
      These 2 causes of death jointly accounted for 51.2% of all deaths of children and
      adolescents in 2008. This annual article is a long-standing feature in Pediatrics
      and provides a summary of the most current vital statistics data for the United
      States. We also include a special feature this year on the differences in
      cesarean-delivery rates according to race and Hispanic origin.

PMID- 21173000
TI  - Adverse events after the use of benznidazole in infants and children with Chagas
      disease.
AB  - BACKGROUND: Chagas disease is caused by infection with Trypanosoma cruzi. In
      adults, treatment with benznidazole is associated with a high incidence of
      adverse drug reactions (ADRs). However, in infants and children, treatment with
      benznidazole seems associated with a lower incidence and decreased severity of
      ADRs, but these effects have not been clearly characterized. OBJECTIVE: We aimed
      to describe ADRs observed in infants and children treated with benznidazole.
      PATIENTS AND METHODS: We conducted a prospective cohort study of infants and
      children in Argentina with Chagas disease treated with benznidazole. RESULTS: A
      total of 107 infants and children diagnosed with asymptomatic Chagas disease
      (mean age: 6.9 years) were enrolled in the study. Sixty-two events (in 44
      children) were considered benznidazole related. Mean ADR duration was 8.2 days.
      ADRs were mild (80.6%), moderate (16%), or severe (3.2%). Most (77.3%) ADRs were
      in children older than 7 years. Skin was the organ with the highest incidence of
      ADRs (21%), followed by the central nervous system (9%) and the gastrointestinal
      tract (8.5%). Also, the ADR rate was lower in infants and toddlers compared with
      older children (18% vs 53%) (P < .001). CONCLUSIONS: Treatment with benznidazole
      was well tolerated in children. Most ADRs were mild and did not require treatment
      suspension. A strong association was observed between ADR incidence and patient
      age, and most ADRs occurred in children older than 7 years. We believe that
      anxiety over potential severe ADRs in children with Chagas disease is not
      justified and should not be an obstacle to using benznidazole.

PMID- 21173004
TI  - Approaches to the difficult patient/parent encounter.
AB  - Most pediatricians have experienced uneasy interactions involving patients and/or
      their parents. The majority of literature on this topic reflects encounters in
      adult medicine, without providing much information for pediatricians who also
      face this challenge. Unique to the pediatric approach is the added quotient of
      the parent/family dynamic. Patients or their parents may have personality
      disorders or subclinical mental health issues, physicians may be overworked or
      have a lack of experience, and the health care system may be overburdened,
      fragmented, and inundated with poor communication. Recognizing the physical or
      emotional responses triggered by challenging patients/families may allow the
      provider to effectively partner with, instead of confront, the patient or the
      family. In this article we review existing literature on this subject and
      describe possible strategies for the pediatrician to use during a difficult
      encounter.

PMID- 21173003
TI  - Tuberous sclerosis complex: diagnostic challenges, presenting symptoms, and
      commonly missed signs.
AB  - OBJECTIVE: To describe presenting symptoms and signs according to age group in a
      cohort of 243 patients with tuberous sclerosis complex (TSC) and identify earlier
      symptoms and signs that did not lead to immediate diagnosis. PATIENTS AND
      METHODS: We performed a retrospective chart review for 278 patients with TSC who
      were examined at Children's Hospital Boston in Massachusetts and at the Herscot
      Center for Tuberous Sclerosis Complex, Massachusetts General Hospital. The
      presenting symptom or sign was the first symptom or sign to cause suspicion for
      TSC and lead to diagnosis. Missed symptoms or signs were those that were
      documented in the patient's chart but did not immediately lead to diagnosis.
      RESULTS: There were 243 patients for whom there were sufficient data for
      inclusion in this study. Patients were diagnosed with TSC at ages ranging from
      birth to 73 years. The average age at diagnosis was 7.5 years. Of the patients,
      81% were diagnosed before the age of 10. Diagnosis during adolescence and
      adulthood was not uncommon. The most common presenting symptoms and signs
      included new onset of seizures, history of seizures, infantile spasms, family
      history of TSC, cardiac rhabdomyomas, and hypopigmented macules. Of the patients,
      39% reported missed symptoms or signs of TSC, most commonly seizures (including
      infantile spasms) and dermatologic features. CONCLUSIONS: Many patients had
      symptoms or signs of TSC that did not lead to immediate diagnosis. Clinicians
      should be aware of the myriad potential presenting symptoms and signs of TSC.
      Early diagnosis may reduce morbidity and mortality.

PMID- 21173002
TI  - Economic evaluation of caffeine for apnea of prematurity.
AB  - OBJECTIVE: To determine the cost-effectiveness of treatment with caffeine
      compared with placebo for apnea of prematurity in infants with birth weights less
      than 1250 g, from birth through 18 to 21 months' corrected age. METHODS: We
      undertook a retrospective economic evaluation of the cost per survivor without
      neurodevelopmental impairment by using individual-patient data from the Caffeine
      for Apnea of Prematurity clinical trial (N = 1869). We included direct medical
      costs either to the insurance payer or the hospital but excluded costs to parents
      and society, such as lost productivity. We used a price of $0.21/mg of generic
      caffeine citrate for our base-case analysis. All costs were expressed in 2008
      Canadian dollars and discounted at 3%. The time horizon for this analysis
      extended through 18 to 21 months' corrected age to match the clinical trial.
      RESULTS: The mean cost per infant was $124 466 in the caffeine group and $133 505
      in the placebo group (difference: $9039 [-14 749 to -3375]; adjusted P = .014).
      Cost-effectiveness analysis showed caffeine to be a dominant or "win-win"
      therapy: in >99% of 1000 bootstrap replications of the analysis, caffeine-treated
      infants had simultaneously better outcomes and lower mean costs. These results
      were robust to a 1000% increase in the individual resource items, including the
      price of caffeine citrate. CONCLUSIONS: In comparison with placebo, caffeine
      therapy for apnea of prematurity in infants weighing less than 1250 g is
      economically appealing for infants up to 18 to 21 months' corrected age.

PMID- 21173005
TI  - Longitudinal study of physical activity and sedentary behavior in children.
AB  - OBJECTIVE: Physical activity is thought to decline during childhood, but the
      extent of the decline is unknown. We made objective measures of 2-year changes in
      physical activity and sedentary behavior in English children who participated in
      the Gateshead Millennium Study to explore the nature, timing, and extent of
      changes in physical activity and sedentary behavior before adolescence. METHODS:
      We conducted a longitudinal study of 405 children (207 girls), aged 7 years, in
      2006/2007 and again 24 months later. Physical activity and sedentary behavior
      were measured with the Actigraph GT1M accelerometer. Data were analyzed in 2010.
      Changes in total volume of physical activity (accelerometer counts per minute
      [cpm]), moderate-to-vigorous-intensity physical activity (MVPA), and sedentary
      behavior were quantified. Factors associated with changes in physical activity
      and sedentary behavior were tested by using linear regression. Tracking of
      physical activity and sedentary behavior over the 2-year period was assessed by
      rank-order correlation. RESULTS: Mean daily volume of physical activity declined
      by 83 cpm (interquartile range [IQR]: -189 to 31) over 2 years; the percentage of
      daily time spent in MVPA was low at baseline and declined by 0.3% (IQR: -1.4 to
      0.9). The percentage of daily time in sedentary behavior was high at baseline and
      increased from 78.0% to 81.1% of the day (change 3.1% [IQR: -0.3 to 6.0]). The
      decline in MVPA and increase in sedentary behavior were significantly greater in
      girls and in those with higher BMI z scores at baseline. Physical activity and
      sedentary behavior showed moderate tracking over the 2-year period. CONCLUSIONS:
      We report here new evidence of low and declining levels of physical activity and
      MVPA and increasing sedentary behavior before adolescence.

PMID- 21173006
TI  - Enhanced monitoring improves pediatric transport outcomes: a randomized
      controlled trial.
AB  - BACKGROUND: The "golden-hour" concept has led to emphasis on speed of patient
      delivery during pediatric interfacility transport. Timely intervention, in
      addition to enhanced monitoring during transport, is the key to improved outcomes
      in critically ill patients. Taking the ICU to the patient may be more beneficial
      than rapid delivery to a tertiary care center. METHODS: The Improved Monitoring
      During Pediatric Interfacility Transport trial was the first randomized
      controlled trial in the out-of-hospital pediatric transport environment. It was
      designed to determine the impact of improved blood pressure monitoring during
      pediatric interfacility transport and the effect on clinical outcomes in patients
      with systemic inflammatory response syndrome and moderate-to-severe head trauma.
      Patients in the control group had their blood pressure monitored intermittently
      with an oscillometric device; those in the intervention group had their blood
      pressure monitored every 12 to 15 cardiac contractions with a near-continuous,
      noninvasive device. RESULTS: Between May 2006 and June 2007, 1995, consecutive
      transport patients were screened, and 94 were enrolled (48 control, 46
      intervention). Patients in the intervention group received more intravenous fluid
      (19.8 +/- 22.2 vs 9.9 +/- 9.9 mL/kg; P = .01), had a shorter hospital stay (6.8
      +/- 7.8 vs 10.9 +/- 13.4 days; P = .04), and had less organ dysfunction (18 of
      206 vs 32 of 202 PICU days; P = .03). CONCLUSIONS: Improved monitoring during
      pediatric transport has the potential to improve outcomes of critically ill
      children. Clinical trials, including randomized controlled trials, can be
      accomplished during pediatric transport. Future studies should evaluate optimal
      equipment, protocols, procedures, and interventions during pediatric transport,
      aimed at improving the clinical and functional outcomes of critically ill
      patients.

PMID- 21173007
TI  - Excess weight loss in first-born breastfed newborns relates to maternal
      intrapartum fluid balance.
AB  - OBJECTIVES: The objectives were to describe weight loss in a multiethnic
      population of first-born, predominantly breastfed, term infants and to identify
      potentially modifiable risk factors for excess weight loss (EWL). METHODS: Data
      on prenatal breastfeeding intentions, demographic characteristics, labor and
      delivery interventions and outcomes, breastfeeding behaviors, formula and
      pacifier use, onset of lactogenesis, and nipple type and pain were collected
      prospectively. Logistic regression analyses identified independent predictors of
      EWL (>=10% of birth weight) by using a preplanned theoretical model. RESULTS: EWL
      occurred for 18% of infants who received no or minimal (<=60 mL total since
      birth) formula (n = 229), including 19% of exclusively breastfed infants (n =
      134) and 16% of infants who received minimal formula (n = 95). In bivariate
      analyses, EWL was associated (P < .05) with higher maternal age, education, and
      income levels, hourly intrapartum fluid balance, postpartum edema, delayed
      lactogenesis (>72 hours), fewer infant stools, and infant birth weight. In
      multivariate logistic regression analysis, only 2 variables predicted EWL
      significantly, namely, intrapartum fluid balance (adjusted relative risk for EWL
      of 3.18 [95% confidence interval [CI]: 1.35-13.29] and 2.80 [95% CI: 1.17-11.68]
      with net intrapartum fluid balance of >200 and 100-200 mL/hour, respectively,
      compared with <100 mL/hour) and delayed lactogenesis (adjusted relative risk:
      3.35 [95% CI: 1.74-8.10]). CONCLUSIONS: EWL was more common in this population
      than reported previously and was independently related to intrapartum fluid
      balance. This suggests that intrapartum fluid administration can cause fetal
      volume expansion and greater fluid loss after birth, although other mechanisms
      are possible.

PMID- 21173008
TI  - Sleep quality evaluation, chronotype, sleepiness and anxiety of Paralympic
      Brazilian athletes: Beijing 2008 Paralympic Games.
AB  - OBJECTIVE: The objective of this study was to evaluate the sleep quality,
      sleepiness, chronotype and the anxiety level of Brazilian Paralympics athletes
      before the 2008 Beijing Paralympic Games. DESIGN: Cross-sectional study. Setting
      Exercise and Psychobiology Studies Center (CEPE) and Universidade Federal de Sao
      Paulo, an urban city in Brazil. PARTICIPANTS: A total of 27 Paralympics athletes
      of both genders (16 men and 11 women) with an average age of 28+/-6 years who
      practised athletics (track and field events) were evaluated. MAIN OUTCOME
      MEASURES: Sleep quality was evaluated using the Pittsburgh Scale and the Epworth
      Sleepiness Scale to evaluate sleepiness. Chronotype was determined by the Horne
      and Ostberg questionnaire and anxiety through the State-Trait Anxiety Inventory.
      The evaluations were performed in Brazil 10 days before the competition. RESULTS:
      The study's results demonstrate that 83.3% of the athletes that presented
      excessive daytime sleepiness also had poor sleep quality. The authors noted that
      71.4% were classified into the morning type and 72% of the athletes who presented
      a medium anxiety level also presented poor sleep quality. Athletes with poor
      sleep quality showed significantly lower sleep efficiency (p=0.0119) and greater
      sleep latency (p=0.0068) than athletes with good sleep quality. Athletes who
      presented excessive daytime sleepiness presented lower sleep efficiency compared
      to non-sleepy athletes (p=0.0241). CONCLUSIONS: The authors conclude that the
      majority of athletes presented poor sleep quality before the competition. This
      information should be taken into consideration whenever possible when scheduling
      rest, training and competition times.

PMID- 21173009
TI  - Comparison study of growth plate fusion using MRI versus plain radiographs as
      used in age determination for exclusion of overaged football players.
AB  - BACKGROUND: MRI of distal radius fusion is currently being used in the U17 World
      Cup to exclude overaged players. Developing countries that cannot afford to
      perform MRI on their players are using plain radiographs based on the same MRI
      criteria of fusion. OBJECTIVE: The aim of this study is to compare the grade of
      fusion of the left wrist distal radial growth plate between MRI and plain
      radiographs. METHODS: 150 healthy male football players were grouped into five
      age groups ranging from 15 to 19 years old. Each participant had coronal T1
      weighted MRI and plain radiograph of the left wrist. The degree of distal radius
      fusion was rated randomly by three radiologists using a six-stage grading system
      proposed by the FIFA Research Centre. RESULTS: MRI assessment of distal radial
      growth plate fusion has good correlation with plain radiograph fusion (r=0.949).
      The mean of x-ray grading is higher than the MRI grading in the 15, 16, 17, 18
      and 19 years old age groups with p=0.443, 0.001, 0.009, <0.001 and 0.003,
      respectively, using Wilcoxon signed ranked test. Intraobserver and interobserver
      correlations were high (r=0.9). T1 MRI correlation with chronological age
      (r=0.771) was close to plain radiographs (r=0.821) with p value of <0.001.
      CONCLUSION: This article is of major importance as it is the first to show that x
      rays significantly overrate the grading of fusion in this age group and therefore
      should not be used to exclude overaged players as is occurring now to the
      distress of many genuinely eligible players.

PMID- 21173011
TI  - Perinatal drug exposure and renal function in very preterm infants.
AB  - OBJECTIVE: To determine the impact on glomerular filtration rate (GFR) and
      tubular function of drugs prescribed to very preterm infants during the first
      week of life. DESIGN: Prospective multicentre cohort study of infants aged 27-31
      weeks gestation. METHODS: GFR was measured on day 2, and then weekly for 1 month,
      with 12-h urine collection by a standardised kinetic Jaffe method. Infants were
      classified into two groups according to their GFR on day 7 ('Low GFR' and 'High
      GFR') with regard to the median reference GFR for their gestational age. Tubular
      function was also measured weekly for 1 month. Statistical analysis was performed
      using logistic regression and a repeated measure analysis. RESULTS: Data from 269
      infants were analysed, 183 in the 'Low GFR' group and 86 in the 'High GFR' group.
      Perinatal factors did not differ in both groups. Significantly more infants were
      treated with ibuprofen in the 'Low GFR' group than in the 'High GFR' group,
      respectively, n=55 (30.0%) versus n=15 (17.4%), whereas aminoglycosides,
      glycopeptides and all other drugs commonly prescribed during the first week of
      life did not show a nephrotoxic effect at usual therapeutic dosage. CONCLUSIONS:
      Among all drugs described as nephrotoxic in very preterm infants, ibuprofen alone
      proved to be nephrotoxic in this study for a 1-month span follow-up. If GFR is
      lower than the median reference value on day 7 after ibuprofen infusion,
      physicians should keep in mind that glomerular clearance of drugs may stay
      decreased for the first month of life.

PMID- 21173012
TI  - Presence of lymphocyte aggregates in the synovium of patients with early
      arthritis in relationship to diagnosis and outcome: is it a constant feature over
      time?
AB  - OBJECTIVES: To evaluate the presence of lymphocyte aggregates in synovial tissue
      of patients with early arthritis in relationship to clinical outcome and to
      determine whether this is a stable feature over time. METHODS: Arthroscopic
      synovial biopsy samples were collected in a prospective cohort of disease
      modifying antirheumatic drug-naive patients with early arthritis (<1 year's
      disease duration) at baseline (n=93) and, if rheumatoid arthritis was suspected,
      after 6 months of follow-up (n=17). After 2 years of follow-up, definitive
      diagnosis and clinical outcome were assessed. Size of synovial lymphocyte
      aggregates was graded (score 1-3). Lymphoid neogenesis (LN) was defined by the
      presence of grade >=2 aggregates and subclassified based on the presence of
      follicular dendritic cells (FDCs). RESULTS: LN was present in 36% of all patients
      and FDCs in 15% of patients with LN. Presence of lymphocyte aggregates differed
      over time. LN was associated with the degree of synovial inflammation. There was
      no relationship between the presence of lymphocyte aggregates at baseline and
      definitive diagnosis or clinical outcome after follow-up. CONCLUSIONS: Presence
      of lymphocyte aggregates is a dynamic phenomenon related to the degree of
      synovitis and can be detected in different forms of early arthritis. This feature
      does not appear to be related to clinical outcome.

PMID- 21173014
TI  - The paediatric wrist revisited: redefining MR findings in healthy children.
AB  - OBJECTIVES: During a multicentre study on juvenile idiopathic arthritis, wide
      variations were observed in bone shape, signal intensity and volume of joint
      fluid as shown by MRI which in part appeared to be unrelated to disease activity.
      A study was undertaken to examine these features in a cohort of healthy children.
      METHODS: 88 children of mean age 9.8 years (range 5-15) underwent MRI imaging (T1
      weighted Spin Echo and Spectral Selection Attenuated Inversion Recovery (SPAIR))
      of the left wrist. The number of bony depressions, distribution and amount of
      joint fluid and the presence of bone marrow changes were assessed. RESULTS: Bony
      depressions were present in all children, increasing with age from a mean of 4.0
      in children aged 4-6 years to 9.2 in those aged 12-15 years (p<0.001)). 45 of 84
      children (53.6%) had a high signal on SPAIR with a corresponding low signal on T1
      in at least one bone. No associations were seen between bone marrow change
      (present or not) and sex (p=0.827) or sports club membership (p=0.616). All
      children had visible joint fluid in at least one of the joints assessed. No
      associations were seen between the presence of joint fluid and age group, except
      for the radius/scaphoid and capitate-scaphoid joints and a recess lateral to the
      hamate. CONCLUSIONS: It is important to be aware of the high prevalence of bony
      depressions, signal changes suggestive of bone marrow oedema and the volume of
      joint fluid seen in normal children. Such findings must be interpreted with care
      in children with suspected disease such as juvenile arthritis.

PMID- 21173013
TI  - A multicentre, randomised, double-blind, placebo-controlled trial with the
      interleukin-1 receptor antagonist anakinra in patients with systemic-onset
      juvenile idiopathic arthritis (ANAJIS trial).
AB  - OBJECTIVES: To assess the efficacy of the interleukin 1 receptor antagonist
      anakinra in systemic-onset juvenile idiopathic arthritis (SJIA). METHODS: A
      multicentre, randomised, double-blind, placebo-controlled trial was conducted.
      The primary objective was to compare the efficacy of a 1-month treatment with
      anakinra (2 mg/kg subcutaneous daily, maximum 100 mg) with a placebo between two
      groups each with 12 patients with SJIA. Response was defined by a 30% improvement
      of the paediatric American College of Rheumatology criteria for JIA, resolution
      of systemic symptoms and a decrease of at least 50% of both C-reactive protein
      and erythrocyte sedimentation rate compared with baseline. After month 1 (M1),
      patients taking placebo were switched to anakinra. Secondary objectives included
      tolerance and efficacy assessment for 12 months, and analyses of treatment effect
      on blood gene expression profiling. RESULTS: At M1, 8/12 responders were
      receiving anakinra and 1 responder receiving placebo (p=0.003). Ten patients from
      the placebo group switched to anakinra; nine were responders at M2. Between M1
      and M12, six patients stopped treatment owing to an adverse event (n=2), lack of
      efficacy (n=2) or a disease flare (n=2). Blood gene expression profiling at
      enrollment and at 6 months' follow-up showed one set of dysregulated genes that
      reverted to normal values in the clinical responders and a different set,
      including interferon (IFN)-inducible genes, that was induced by anakinra.
      CONCLUSIONS: Anakinra treatment is effective in SJIA, at least in the short term.
      It is associated with normalisation of blood gene expression profiles in clinical
      responders and induces a de novo IFN signature. TRIAL REGISTRATION NUMBER:
      NCT00339157.

PMID- 21173015
TI  - Favourable and sustained response to anakinra in tumour necrosis factor receptor
      associated periodic syndrome (TRAPS) with or without AA amyloidosis.

PMID- 21173016
TI  - Global effects of fluvastatin on the prothrombotic status of patients with
      antiphospholipid syndrome.
AB  - OBJECTIVE: Numerous mechanisms have been proposed to explain the
      thrombotic/proinflammatory tendency of antiphospholipid syndrome (APS) patients.
      Prothrombotic monocyte activation by antiphospholipid antibodies involves
      numerous proteins and intracellular pathways. The anti-inflammatory,
      anticoagulant and immunoregulatory effects of statins have been aimed as a
      therapeutic tool in APS patients. This study delineates the global effects of
      fluvastatin on the prothrombotic tendency of monocytes from APS patients.
      METHODS: Forty-two APS patients with thrombosis and 35 healthy donors were
      included in the study. APS patients received 20 mg/day fluvastatin for 1 month.
      Blood samples were obtained before the start, at the end and 2 months after the
      end of treatment. RESULTS: After 1 month of treatment, monocytes showed a
      significant inhibition of tissue factor, protein activator receptors 1 and 2,
      vascular endothelial growth factor and Flt1 expression that was related to the
      inhibition of p38 mitogen-activated protein kinase (MAPK) and nuclear factor
      kappa B/Rel DNA-binding activity. Proteomic analysis showed proteins involved in
      thrombotic development (annexin II, RhoA and protein disulphide isomerase) with
      altered expression after fluvastatin administration. In-vitro studies indicated
      that the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase by
      fluvastatin might inhibit protein prenylation and MAPK activation. CONCLUSION:
      The data from this study support the belief that fluvastatin has multiple
      profound effects in monocyte activity, which might contribute to thrombosis
      prevention in APS patients.

PMID- 21173018
TI  - Role of oxidative stress in rheumatoid arthritis: insights from the Nrf2-knockout
      mice.
AB  - OBJECTIVES: Increasing evidence suggests that oxidative stress may play a key
      role in joint destruction due to rheumatoid arthritis (RA). The aim of this study
      was to elucidate the role of nuclear factor erythroid 2-related factor 2 (Nrf2),
      a transcription factor that maintains the cellular defence against oxidative
      stress, in RA. METHODS: The activation status of Nrf2 was assessed in synovial
      tissue from patients with RA using immunohistochemistry. Antibody-induced
      arthritis (AIA) was induced in Nrf2-knockout and Nrf2-wild-type control mice. The
      severity of cartilage destruction was evaluated using a damage score. The extent
      of oxidative stress, the activation state of Nrf2 and the expression level of
      Nrf2 target genes were analysed by immunhistological staining. The expression of
      vascular endothelial growth factor (VEGF)-A was examined on mRNA and protein
      using the Luminex technique. A Xenogen imaging system was used to measure Nrf2
      activity in an antioxidant response element-luciferase transgenic mouse during
      AIA. RESULTS: Nrf2 was activated in the joints of arthritic mice and of patients
      with RA. Nrf2-knockout mice had more severe cartilage injuries and more oxidative
      damage, and the expression of Nrf2 target genes was enhanced in Nrf2-wild-type
      but not in knockout mice during AIA. Both VEGF-A mRNA and protein expression was
      upregulated in Nrf2-knockout mice during AIA. An unexpected finding was the
      number of spontaneously fractured bones in Nrf2-knockout mice with AIA.
      CONCLUSION: These results provide strong evidence that oxidative stress is
      significantly involved in cartilage degradation in experimental arthritis, and
      indicate that the presence of a functional Nrf2 gene is a major requirement for
      limiting cartilage destruction.

PMID- 21173017
TI  - HSC70 blockade by the therapeutic peptide P140 affects autophagic processes and
      endogenous MHCII presentation in murine lupus.
AB  - BACKGROUND: The P140 phosphopeptide issued from the spliceosomal U1-70K small
      nuclear ribonucleoprotein protein displays protective properties in MRL/lpr lupus
      prone mice. It binds both major histocompatibility class II (MHCII) and
      HSC70/Hsp73 molecules. P140 peptide increases MRL/lpr peripheral blood lymphocyte
      apoptosis and decreases autoepitope recognition by T cells. OBJECTIVE: To explore
      further the mode of action of P140 peptide on HSC70+ antigen-presenting cells.
      METHODS: P140 biodistribution was monitored in real time using an imaging system
      and by fluorescence and electron microscopy. Fluorescence activated cell sorting
      and Western blotting experiments were used to evaluate the P140 effects on
      autophagic flux markers. RESULTS: P140 fluorescence accumulated especially in the
      lungs and spleen. P140 peptide reduced the number of peripheral and splenic T and
      B cells without affecting these cells in normal mice. Remaining MRL/lpr B cells
      responded normally to mitogens. P140 peptide decreased the expression levels of
      HSC70/Hsp73 chaperone and stable MHCII dimers, which are both increased in
      MRL/lpr splenic B cells. It impaired refolding properties of chaperone HSC70. In
      MRL/lpr B cells, it increased the accumulation of the autophagy markers
      p62/SQSTM1 and LC3-II, consistent with a downregulated lysosomal degradation
      during autophagic flux. CONCLUSION: The study results suggest that after P140
      peptide binding to HSC70, the endogenous (auto)antigen processing might be
      greatly affected in MRL/lpr antigen-presenting B cells, leading to the observed
      decrease of autoreactive T-cell priming and signalling via a mechanism involving
      a lysosomal degradation pathway. This unexpected mechanism might explain the
      beneficial effect of P140 peptide in treated MRL/lpr mice.

PMID- 21173019
TI  - Successful use of bortezomib in a patient with systemic lupus erythematosus and
      multiple myeloma.

PMID- 21173020
TI  - Prenatal androgen treatment alters body composition and glucose homeostasis in
      male rats.
AB  - Prenatal androgen produces many reproductive and metabolic features of polycystic
      ovary syndrome in female rodents, sheep, and monkeys. We investigated the impact
      of such prenatal treatment in adult male rats. Pregnant dams received free
      testosterone (T; aromatizable androgen), dihydrotestosterone (D; nonaromatizable
      androgen), or vehicle control (C) on embryonic days 16-19. Neither of the
      prenatal androgen treatments resulted in increased body weight from weaning to
      age 65 days in males. However, at 65 days, there were significant increases in
      retroperitoneal (P < 0.001 T versus C; P < 0.05 D versus C), epididymal (P < 0.05
      T versus C), and subcutaneous (P < 0.01 T versus C) fat pads in prenatally
      androgenized males. While both androgens altered body composition, subcutaneous
      fat depots increased only in T males. T males had elevated glucose levels (P <
      0.01) compared to C males. There were no differences among the three groups in
      insulin sensitivity, circulating lipid and leptin levels, or hepatic triglyceride
      content. Real-time PCR analysis of insulin signaling pathway genes in
      retroperitoneal fat revealed a transcriptional downregulation of adipsin and
      insulin receptor substrate-1 in T and alpha-1D adrenergic receptor in D compared
      to C males. We conclude that transient exposure to androgen excess in utero
      increases body fat in adult male rats. Only T males exhibit increased circulating
      glucose levels and subcutaneous fat suggesting that these changes may be mediated
      by aromatization of androgen to estrogen rather than by direct androgenic
      actions.

PMID- 21173021
TI  - Unique thylakoid membrane architecture of a unicellular N2-fixing cyanobacterium
      revealed by electron tomography.
AB  - Cyanobacteria, descendants of the endosymbiont that gave rise to modern-day
      chloroplasts, are vital contributors to global biological energy conversion
      processes. A thorough understanding of the physiology of cyanobacteria requires
      detailed knowledge of these organisms at the level of cellular architecture and
      organization. In these prokaryotes, the large membrane protein complexes of the
      photosynthetic and respiratory electron transport chains function in the
      intracellular thylakoid membranes. Like plants, the architecture of the thylakoid
      membranes in cyanobacteria has direct impact on cellular bioenergetics, protein
      transport, and molecular trafficking. However, whole-cell thylakoid organization
      in cyanobacteria is not well understood. Here we present, by using electron
      tomography, an in-depth analysis of the architecture of the thylakoid membranes
      in a unicellular cyanobacterium, Cyanothece sp. ATCC 51142. Based on the results
      of three-dimensional tomographic reconstructions of near-entire cells, we
      determined that the thylakoids in Cyanothece 51142 form a dense and complex
      network that extends throughout the entire cell. This thylakoid membrane network
      is formed from the branching and splitting of membranes and encloses a single
      lumenal space. The entire thylakoid network spirals as a peripheral ring of
      membranes around the cell, an organization that has not previously been described
      in a cyanobacterium. Within the thylakoid membrane network are areas of quasi
      helical arrangement with similarities to the thylakoid membrane system in
      chloroplasts. This cyanobacterial thylakoid arrangement is an efficient means of
      packing a large volume of membranes in the cell while optimizing intracellular
      transport and trafficking.

PMID- 21173023
TI  - Loss-of-function and gain-of-function mutations in FAB1A/B impair endomembrane
      homeostasis, conferring pleiotropic developmental abnormalities in Arabidopsis.
AB  - In eukaryotic cells, PtdIns 3,5-kinase, Fab1/PIKfyve produces PtdIns (3,5) P(2)
      from PtdIns 3-P, and functions in vacuole/lysosome homeostasis. Herein, we show
      that expression of Arabidopsis (Arabidopsis thaliana) FAB1A/B in fission yeast
      (Schizosaccharomyces pombe) fab1 knockout cells fully complements the vacuole
      morphology phenotype. Subcellular localizations of FAB1A and FAB1B fused with
      green fluorescent protein revealed that FAB1A/B-green fluorescent proteins
      localize to the endosomes in root epidermal cells of Arabidopsis. Furthermore,
      reduction in the expression levels of FAB1A/B by RNA interference impairs
      vacuolar acidification and endocytosis. These results indicate that Arabidopsis
      FAB1A/B functions as PtdIns 3,5-kinase in plants and in fission yeast.
      Conditional knockdown mutant shows various phenotypes including root growth
      inhibition, hyposensitivity to exogenous auxin, and disturbance of root
      gravitropism. These phenotypes are observed also in the overproducing mutants of
      FAB1A and FAB1B. The overproducing mutants reveal additional morphological
      phenotypes including dwarfism, male-gametophyte sterility, and abnormal floral
      organs. Taken together, this evidence indicates that imbalanced expression of
      FAB1A/B impairs endomembrane homeostasis including endocytosis, vacuole
      formation, and vacuolar acidification, which causes pleiotropic developmental
      phenotypes mostly related to the auxin signaling in Arabidopsis.

PMID- 21173022
TI  - Arabidopsis homologs of the petunia hairy meristem gene are required for
      maintenance of shoot and root indeterminacy.
AB  - Maintenance of indeterminacy is fundamental to the generation of plant
      architecture and a central component of the plant life strategy. Indeterminacy in
      plants is a characteristic of shoot and root meristems, which must balance
      maintenance of indeterminacy with organogenesis. The Petunia hybrida HAIRY
      MERISTEM (HAM) gene, a member of the GRAS family of transcriptional regulators,
      promotes shoot indeterminacy by an undefined non-cell-autonomous signaling
      mechanism(s). Here, we report that Arabidopsis (Arabidopsis thaliana) mutants
      triply homozygous for knockout alleles in three Arabidopsis HAM orthologs
      (Atham1,2,3 mutants) exhibit loss of indeterminacy in both the shoot and root. In
      the shoot, the degree of penetrance of the loss-of-indeterminacy phenotype of
      Atham1,2,3 mutants varies among shoot systems, with arrest of the primary
      vegetative shoot meristem occurring rarely or never, secondary shoot meristems
      typically arresting prior to initiating organogenesis, and inflorescence and
      flower meristems exhibiting a phenotypic range extending from wild type (flowers)
      to meristem arrest preempting organogenesis (flowers and inflorescence).
      Atham1,2,3 mutants also exhibit aberrant shoot phyllotaxis, lateral organ
      abnormalities, and altered meristem morphology in functioning meristems of both
      rosette and inflorescence. Root meristems of Atham1,2,3 mutants are significantly
      smaller than in the wild type in both longitudinal and radial axes, a consequence
      of reduced rates of meristem cell division that culminate in root meristem
      arrest. Atham1,2,3 phenotypes are unlikely to reflect complete loss of HAM
      function, as a fourth, more distantly related Arabidopsis HAM homolog, AtHAM4,
      exhibits overlapping function with AtHAM1 and AtHAM2 in promoting shoot
      indeterminacy.

PMID- 21173024
TI  - Three homologous genes encoding sn-glycerol-3-phosphate acyltransferase 4 exhibit
      different expression patterns and functional divergence in Brassica napus.
AB  - Brassica napus is an allotetraploid (AACC) formed from the fusion of two diploid
      progenitors, Brassica rapa (AA) and Brassica oleracea (CC). Polyploidy and genome
      wide rearrangement during the evolution process have resulted in genes that are
      present as multiple homologs in the B. napus genome. In this study, three B.
      napus homologous genes encoding endoplasmic reticulum-bound sn-glycerol-3
      phosphate acyltransferase 4 (GPAT4) were identified and characterized. Although
      the three GPAT4 homologs share a high sequence similarity, they exhibit different
      expression patterns and altered epigenetic features. Heterologous expression in
      yeast further revealed that the three BnGPAT4 homologs encoded functional GPAT
      enzymes but with different levels of polypeptide accumulation. Complementation of
      the Arabidopsis (Arabidopsis thaliana) gpat4 gpat8 double mutant line with
      individual BnGPAT4 homologs suggested their physiological roles in cuticle
      formation. Analysis of gpat4 RNA interference lines of B. napus revealed that the
      BnGPAT4 deficiency resulted in reduced cutin content and altered stomatal
      structures in leaves. Our results revealed that the BnGPAT4 homologs have evolved
      into functionally divergent forms and play important roles in cutin synthesis and
      stomatal development.

PMID- 21173025
TI  - iTRAQ protein profile analysis of Arabidopsis roots reveals new aspects critical
      for iron homeostasis.
AB  - Iron (Fe) deficiency is a major constraint for plant growth and affects the
      quality of edible plant parts. To investigate the mechanisms underlying Fe
      homeostasis in plants, Fe deficiency-induced changes in the protein profile of
      Arabidopsis (Arabidopsis thaliana) roots were comprehensively analyzed using
      iTRAQ (Isobaric Tag for Relative and Absolute Quantification) differential liquid
      chromatography-tandem mass spectrometry on a LTQ-Orbitrap with high-energy
      collision dissociation. A total of 4,454 proteins were identified with a false
      discovery rate of less than 1.1%, and 2,882 were reliably quantified. A subset of
      101 proteins was differentially expressed upon Fe deficiency. The changes in
      protein profiles upon Fe deficiency show low congruency with previously reported
      alterations in transcript levels, indicating posttranscriptional changes, and
      provide complementary information on Fe deficiency-induced processes. The
      abundance of proteins involved in the synthesis/regeneration of S
      adenosylmethionine, the phenylpropanoid pathway, the response to oxidative
      stress, and respiration was highly increased by Fe deficiency. Using Fe
      responsive proteins as bait, genome-wide fishing for partners with predictable or
      confirmed interologs revealed that RNA processing and ribonucleoprotein complex
      assembly may represent critical processes that contribute to the regulation of
      root responses to Fe deficiency, possibly by biasing translation efficiency.

PMID- 21173026
TI  - Castor phospholipid:diacylglycerol acyltransferase facilitates efficient
      metabolism of hydroxy fatty acids in transgenic Arabidopsis.
AB  - Producing unusual fatty acids (FAs) in crop plants has been a long-standing goal
      of green chemistry. However, expression of the enzymes that catalyze the primary
      synthesis of these unusual FAs in transgenic plants typically results in low
      levels of the desired FA. For example, seed-specific expression of castor
      (Ricinus communis) fatty acid hydroxylase (RcFAH) in Arabidopsis (Arabidopsis
      thaliana) resulted in only 17% hydroxy fatty acids (HFAs) in the seed oil. In
      order to increase HFA levels, we investigated castor phospholipid:diacylglycerol
      acyltransferase (PDAT). We cloned cDNAs encoding three putative PDAT enzymes from
      a castor seed cDNA library and coexpressed them with RcFAH12. One isoform,
      RcPDAT1A, increased HFA levels to 27%. Analysis of HFA-triacylglycerol molecular
      species and regiochemistry, along with analysis of the HFA content of
      phosphatidylcholine, indicates that RcPDAT1A functions as a PDAT in vivo.
      Expression of RcFAH12 alone leads to a significant decrease in FA content of
      seeds. Coexpression of RcPDAT1A and RcDGAT2 (for diacylglycerol acyltransferase
      2) with RcFAH12 restored FA levels to nearly wild-type levels, and this was
      accompanied by a major increase in the mass of HFAs accumulating in the seeds. We
      show the usefulness of RcPDAT1A for engineering plants with high levels of HFAs
      and alleviating bottlenecks due to the production of unusual FAs in transgenic
      oilseeds.

PMID- 21173027
TI  - The role of Arabidopsis Rubisco activase in jasmonate-induced leaf senescence.
AB  - Leaf senescence, as the last stage of leaf development, is regulated by diverse
      developmental and environmental factors. Jasmonates (JAs) have been shown to
      induce leaf senescence in several plant species; however, the molecular mechanism
      for JA-induced leaf senescence remains unknown. In this study, proteomic,
      genetic, and physiological approaches were used to reveal the molecular basis of
      JA-induced leaf senescence in Arabidopsis (Arabidopsis thaliana). We identified
      35 coronatine-insensitive 1 (COI1)-dependent JA-regulated proteins using two
      dimensional difference gel electrophoresis in Arabidopsis. Among these 35
      proteins, Rubisco activase (RCA) was a COI1-dependent JA-repressed protein. We
      found that RCA was down-regulated at the levels of transcript and protein
      abundance by JA in a COI1-dependent manner. We further found that loss of RCA led
      to typical senescence-associated features and that the COI1-dependent JA
      repression of RCA played an important role in JA-induced leaf senescence.

PMID- 21173028
TI  - MYCN sensitizes human neuroblastoma to apoptosis by HIPK2 activation through a
      DNA damage response.
AB  - MYCN amplification occurs in approximately 20% of human neuroblastomas and is
      associated with early tumor progression and poor outcome, despite intensive
      multimodal treatment. However, MYCN overexpression also sensitizes neuroblastoma
      cells to apoptosis. Thus, uncovering the molecular mechanisms linking MYCN to
      apoptosis might contribute to designing more efficient therapies for MYCN
      amplified tumors. Here we show that MYCN-dependent sensitization to apoptosis
      requires activation of p53 and its phosphorylation at serine 46. The p53(S46)
      kinase HIPK2 accumulates on MYCN expression, and its depletion by RNA
      interference impairs p53(S46) phosphorylation and apoptosis. Remarkably, MYCN
      induces a DNA damage response that accounts for the inhibition of HIPK2
      degradation through an ATM- and NBS1-dependent pathway. Prompted by the rare
      occurrence of p53 mutations and by the broad expression of HIPK2 in our human
      neuroblastoma series, we evaluated the effects of the p53-reactivating compound
      Nutlin-3 on this pathway. At variance from other tumor histotypes, in MYCN
      amplified neuroblastoma, Nutlin-3 further induced HIPK2 accumulation, p53(S46)
      phosphorylation, and apoptosis, and in combination with clastogenic agents purged
      virtually the entire cell population. Altogether, our data uncover a novel
      mechanism linking MYCN to apoptosis that can be triggered by the p53-reactivating
      compound Nutlin-3, supporting its use in the most difficult-to-treat subset of
      neuroblastoma.

PMID- 21173029
TI  - Consumption of bitter alkaloids in Drosophila melanogaster in multiple-choice
      test conditions.
AB  - Drosophila melanogaster adapt their food consumption to their internal needs and
      avoid ingesting noxious molecules. Defects in the genes involved in these
      decisions induce behavioral alterations that are usually screened by monitoring
      flies feeding in 2-choice or in no-choice situations. Here, we introduce a new
      behavioral test in which groups of flies are given access to 6 capillary feeders
      (MultiCAFE) containing fructose mixed with a serial dilution of a test substance.
      Using quinine, we first showed that fly density, distance between capillaries,
      and order of presentation have a minor impact on the discrimination performances
      of the flies. Fly discrimination was also only marginally affected by the type of
      test (no-choice, binary, or multiple-choice). Interestingly, the feeding
      reduction was well correlated with a reduction of the firing elicited by the
      mixture in sugar-sensitive gustatory receptor neurons, suggesting that several
      mechanisms concur to allow flies to make their choices. In addition to quinine,
      flies exhibited marked dose-dependent aversions to the consumption of berberine,
      caffeine, lobeline, nicotine, papaverine, strychnine, and theophylline, which all
      taste bitter to humans. Thus, despite of the multiplicity of choices available,
      flies consistently avoid alkaloids mixed with a sugar solution, and their choices
      are strongly dependent on their taste system. The MultiCAFE assay represents an
      interesting alternative to other feeding tests, in that it allows monitoring of
      the absolute consumption while also requiring less flies and time to run than
      other assays.

PMID- 21173030
TI  - The use of debonding microspheres in electrothermal debonding.
AB  - The aim of this study was to investigate if debonding microspheres (DM) could
      enhance electrothermal orthodontic debonding, and specifically to evaluate if the
      addition of DM, in varying concentrations to the orthodontic adhesive process,
      will affect bond strength. Bovine teeth (n=8) were mounted in acrylic using a
      silicone mould. Four test groups of three preparations of primer (Rely-a-Bond)
      with DM and a control were examined. Five incisor brackets were bonded to each
      tooth using the assigned primer and cold cure composite (Rely-a-Bond). Bracket
      tensile bond strength was measured in vitro in an Instron machine and recorded as
      debonding force (N). Differences between the groups were statistically analysed
      using analysis of variance, and repeatability was assessed. The mean debonding
      force of the control group was statistically significantly greater than all the
      other groups to which DM had been added (P<0.001). Comparison of the mean
      debonding forces of 1, 2.5, and 5 per cent concentrations of DM revealed no
      statistically significant difference between the groups. The addition of DM to
      orthodontic adhesive produced a highly statistically significant reduction in
      debonding force. There was no statistical difference in debonding force between
      varying concentrations of DM.

PMID- 21173032
TI  - Age-dependent gain of alternative splice forms and biased duplication explain the
      relation between splicing and duplication.
AB  - We analyze here the relation between alternative splicing and gene duplication in
      light of recent genomic data, with a focus on the human genome. We show that the
      previously reported negative correlation between level of alternative splicing
      and family size no longer holds true. We clarify this pattern and show that it is
      sufficiently explained by two factors. First, genes progressively gain new splice
      variants with time. The gain is consistent with a selectively relaxed regime,
      until purifying selection slows it down as aging genes accumulate a large number
      of variants. Second, we show that duplication does not lead to a loss of splice
      forms, but rather that genes with low levels of alternative splicing tend to
      duplicate more frequently. This leads us to reconsider the role of alternative
      splicing in duplicate retention.

PMID- 21173031
TI  - Bubble-chip analysis of human origin distributions demonstrates on a genomic
      scale significant clustering into zones and significant association with
      transcription.
AB  - We have used a novel bubble-trapping procedure to construct nearly pure and
      comprehensive human origin libraries from early S- and log-phase HeLa cells, and
      from log-phase GM06990, a karyotypically normal lymphoblastoid cell line. When
      hybridized to ENCODE tiling arrays, these libraries illuminated 15.3%, 16.4%, and
      21.8% of the genome in the ENCODE regions, respectively. Approximately half of
      the origin fragments cluster into zones, and their signals are generally higher
      than those of isolated fragments. Interestingly, initiation events are
      distributed about equally between genic and intergenic template sequences. While
      only 13.2% and 14.0% of genes within the ENCODE regions are actually transcribed
      in HeLa and GM06990 cells, 54.5% and 25.6% of zonal origin fragments overlap
      transcribed genes, most with activating chromatin marks in their promoters. Our
      data suggest that cell synchronization activates a significant number of inchoate
      origins. In addition, HeLa and GM06990 cells activate remarkably different origin
      populations. Finally, there is only moderate concordance between the log-phase
      HeLa bubble map and published maps of small nascent strands for this cell line.

PMID- 21173033
TI  - RNA sequencing reveals the role of splicing polymorphisms in regulating human
      gene expression.
AB  - Expression levels of many human genes are under the genetic control of expression
      quantitative trait loci (eQTLs). Despite technological advances, the precise
      molecular mechanisms underlying most eQTLs remain elusive. Here, we use deep mRNA
      sequencing of two CEU individuals to investigate those mechanisms, with
      particular focus on the role of splicing control loci (sQTLs). We identify a
      large number of genes that are differentially spliced between the two samples and
      associate many of those differences with nearby single nucleotide polymorphisms
      (SNPs). Subsequently, we investigate the potential effect of splicing SNPs on
      eQTL control in general. We find a significant enrichment of alternative splicing
      (AS) events within a set of highly confident eQTL targets discovered in previous
      studies, suggesting a role of AS in regulating overall gene expression levels.
      Next, we demonstrate high correlation between the levels of mature (exonic) and
      unprocessed (intronic) RNA, implying that ~75% of eQTL target variance can be
      explained by control at the level of transcription, but that the remaining 25%
      may be regulated co- or post-transcriptionally. We focus on eQTL targets with
      discordant mRNA and pre-mRNA expression patterns and use four examples: USMG5,
      MMAB, MRPL43, and OAS1, to dissect the exact downstream effects of the associated
      genetic variants.

PMID- 21173035
TI  - Using cerebral oximetry to prevent adverse outcomes during cardiac surgery.
AB  - We report a case of reduced cerebral oxygenation which had the possibility of
      leading to an adverse outcome if it had not been detected by the routine use of
      cerebral oximetry. This case study illustrates that an inadvertent re-adjustment
      of a single-stage venous cannula within the superior vena cava resulted only in
      the cerebral oximetry device alerting to a potential problem. All other
      monitoring devices remained within standard operating parameters, with no
      deviation throughout the duration of the incident.

PMID- 21173034
TI  - Selective ploidy ablation, a high-throughput plasmid transfer protocol,
      identifies new genes affecting topoisomerase I-induced DNA damage.
AB  - We have streamlined the process of transferring plasmids into any yeast strain
      library by developing a novel mating-based, high-throughput method called
      selective ploidy ablation (SPA). SPA uses a universal plasmid donor strain that
      contains conditional centromeres on every chromosome. The plasmid-bearing donor
      is mated to a recipient, followed by removal of all donor-strain chromosomes,
      producing a haploid strain containing the transferred plasmid. As proof of
      principle, we used SPA to transfer plasmids containing wild-type and mutant
      alleles of DNA topoisomerase I (TOP1) into the haploid yeast gene-disruption
      library. Overexpression of Top1 identified only one sensitive mutation, rpa34,
      while overexpression of top1-T(722)A allele, a camptothecin mimetic, identified
      190 sensitive gene-disruption strains along with rpa34. In addition to known
      camptothecin-sensitive strains, this set contained mutations in genes involved in
      the Rpd3 histone deacetylase complex, the kinetochore, and vesicle trafficking.
      We further show that mutations in several ESCRT vesicle trafficking components
      increase Top1 levels, which is dependent on SUMO modification. These findings
      demonstrate the utility of the SPA technique to introduce plasmids into the
      haploid gene-disruption library to discover new interacting pathways.

PMID- 21173036
TI  - Increased cerebral blood flow velocities assessed by transcranial Doppler
      examination is associated with complement activation after cardiopulmonary
      bypass.
AB  - The role of complement activation on the cerebral vasculature after
      cardiopulmonary bypass (CPB) is unclear. The goal of the study was to assess
      whether heparin-coated CPB reduces complement activation, and influences cerebral
      blood flow velocities (CBFV). Twenty-four patients undergoing coronary surgery
      were randomly allocated to non-coated (NC-group) or heparin-coated (HC-group)
      CPB. Complement activation was assessed by measuring sC5b-9. Transcranial Doppler
      (TCD) was performed on middle cerebral arteries before and after CPB. Systolic
      (SV), diastolic (DV) and mean (MV) CBFV were measured. Significant increase of
      sC5b-9 (p=0.003) was observed in the NC-group and CBFV increased after CPB (SV by
      27%, p=0.05; DV by 40%, p=0.06; MV by 33%, p=0.04) whereas no changes were
      detected in the HC-group. TCD values were higher in the NC-group than in the HC
      group (SV, p=0.04; DV, p=0.03; MV, p=0.03) although cardiac index, systemic
      vascular resistance, haematocrit and pCO(2) were similar. Postoperative SV, DV
      and MV were significantly correlated with sC5b-9 (r=0.583, p=0.009; r=0.581,
      p=0.009; r=0.598, p=0.007, respectively). Increased CBFV after CPB are correlated
      to the level of complement activation and may be controlled by heparin-coated
      circuits.

PMID- 21173037
TI  - Aortic arch replacement with moderate hyperthomia and a modified 3-pump circuit.
AB  - A strategy employing moderate hypothermia for replacement of the aortic arch is
      proposed to avoid the complications of profound hypothermic circulatory arrest.
      Two patients underwent complete replacement of the aortic arch using three pumps
      (Figure 1a - one to perfuse the brain, one for the thoracoabdominal aorta and the
      third for the heart). There were no complications and the patients were extubated
      uneventfully. The method preserves autoregulation of cerebral blood flow without
      high vascular resistances.

PMID- 21173038
TI  - An in vitro comparison of the ability of three commonly used pediatric
      cardiopulmonary bypass circuits to filter gaseous microemboli.

PMID- 21173039
TI  - Further characterization of the electrogenicity and pH sensitivity of the human
      organic anion-transporting polypeptides OATP1B1 and OATP1B3.
AB  - Organic anion-transporting polypeptides (OATPs) are involved in the liver uptake
      of many endogenous and xenobiotic compounds, such as bile acids and drugs,
      respectively. Using Xenopus laevis oocytes and Chinese hamster ovary (CHO) cells
      expressing rat Oatp1a1, human OATP1B1, or OATP1B3, the sensitivity of these
      transporters to extracellular/intracellular pH (pHo/pHi) and changes in plasma
      membrane potential (DeltaPsi) was investigated. In X. laevis oocytes, nonspecific
      plasma membrane permeability increased only at pHo below 4.5. Above this value,
      both using oocytes and CHO cells, extracellular acidification affected
      differently the specific transport of taurocholic acid (TCA) and estradiol 17beta
      d-glucuronide (E(2)17betaG) by Oatp1a1 (stimulation), OATP1B1 (inhibition), and
      OATP1B3 (stimulation). Changes in substrate uptake in the presence of valinomycin
      (K(+)-ionophore), carbonyl cyanide 3-chlorophenylhydrazone and nigericin
      (protonophores), and amiloride (Na(+)/H(+)-inhibitor) and cation replacement in
      the medium were studied with fluorescent probes for measuring substrate uptake
      (cholylglycyl amidofluorescein) and changes in pHi (SNARF-4F) and DeltaPsi
      [DilC(1)(5)]. The results suggest that activity of these three carriers is
      sodium/potassium-independent and affected differently by changes in pHo and
      DeltaPsi: Oatp1a1 was confirmed to be an electroneutral anion exchanger, whereas
      the function of both OATP1B1 and OATP1B3 was markedly affected by the magnitude
      of DeltaPsi. Moreover, electrophysiological measurements revealed the existence
      of a net anion influx associated to OATP1B1/OATP1B3-mediated transport of TCA,
      E(2)17betaG, and estrone-3-sulfate. Furthermore, a leakage of Na(+) through
      OATP1B1 and OATP1B3, which is not coupled to substrate transport, was found. In
      conclusion, these results suggest that OATP1B1 and OATP1B3 are electrogenic
      transporters whose activity may be strongly affected under circumstances of
      displacement of local pH.

PMID- 21173040
TI  - Evidence for a second receptor for prostacyclin on human airway epithelial cells
      that mediates inhibition of CXCL9 and CXCL10 release.
AB  - Herein we provide evidence for the coexpression of two distinct prostacyclin
      (PGI(2)) receptors (IP) on BEAS-2B human airway epithelial cells. IP receptor
      heterogeneity initially was suggested by the finding that the rank orders of
      potency of PGI(2) and three structurally similar analogs [taprostene, iloprost,
      15-deoxy-16-(m-tolyl)-17,18,19,20-tetranorisocarbacyclin (15-deoxy-TIC)] for the
      inhibition of chemokine (CXCL9 and CXCL10) release and for transcriptional
      activation/augmentation of cAMP response element and glucocorticoid response
      element luciferase reporters were distinct. Indeed, PGI(2), taprostene, and
      iloprost activated both reporters whereas 15-deoxy-TIC was inert. Conversely, 15
      deoxy-TIC, PGI(2), and taprostene (but not iloprost) suppressed chemokine
      release. Further experiments established that iloprost did not antagonize the
      inhibitory effect taprostene or 15-deoxy-TIC on chemokine output. Likewise, 15
      deoxy-TIC failed to antagonize taprostene- and iloprost-induced reporter
      transactivation. Thus, iloprost- and 15-deoxy-TIC-induced responses were
      apparently mediated via pharmacologically distinct receptors. In human embryonic
      kidney 293 cells overexpressing the human recombinant IP receptor receptor, 15
      deoxy-TIC was considerably less potent (>10,000-fold) than iloprost and
      taprostene in promoting cAMP accumulation, yet in BEAS-2B cells, these analogs
      were equipotent. IP receptor heterogeneity was also supported by the finding that
      the affinity of the IP receptor antagonist R-3-(4-fluorophenyl)-2-[5-(4
      fluorophenyl)-benzofuran-2-yl-methoxycarbonyl-amino] propionic acid (RO3244794)
      for the receptor mediating inhibition of chemokine release was approximately 10
      fold lower than for the receptor mediating both transcriptional outputs. Finally,
      small interfering RNAs directed against the IP receptor gene, PTGIR, failed to
      block the suppression of chemokine output induced by taprostene and 15-deoxy-TIC,
      whereas taprostene- and iloprost-induced transcriptional responses were markedly
      attenuated. Collectively, these results indicate that PGI(2), taprostene and 15
      deoxy-TIC suppress chemokine release from BEAS-2B cells by interacting with a
      novel IP receptor that we denote here as the "IP(2)" subtype.

PMID- 21173042
TI  - The history of registered sickness absence predicts future sickness absence.
AB  - BACKGROUND: The history of sickness absence has been found to predict future
      sickness absence. AIMS: To establish the review period of historical sickness
      absence data that is needed to predict future sickness absence. METHODS: The
      individual number of days and episodes of sickness absence were ascertained for
      762 hospital employees from 2004 to 2008 inclusive. Past sickness absence was
      included stepwise in ordinal regression models. The explained variance of the
      ordinal regression models reflected the extent to which future sickness absence
      could be predicted and was expressed in percentages calculated as Nagelkerke's
      pseudo R(2) * 100%. RESULTS: A total of 551 employees (72%) had complete data and
      were eligible for regression analysis. Days of sickness absence in the past year
      predicted up to 15% of future days of sickness absence. Adding the sickness
      absence data of the past 2 or 3 years did not further increase the predictability
      of days of sickness absence. Episodes of sickness absence in the past year
      predicted up to 25% of future episodes of sickness absence. The predictability of
      episodes of sickness absence increased to 30% when the past 2 years of sickness
      absence were included in the regression model, but did not further increase when
      sickness absence of the past 3 years was included. CONCLUSIONS: Employees who are
      more likely to have an above average sickness absence can be identified from
      their history of sickness absence in the past 2 years.

PMID- 21173041
TI  - Flapping loops: roles for hinges in a ligand-binding domain of the nicotinic
      receptor.
AB  - One of the goals of molecular pharmacology is to understand the machinery that
      converts information about the presence of a chemical (binding) to a functional
      consequence. Agonists are drugs that bind to their molecular targets and cause
      conformational changes underlying activation of the target. Inevitably,
      therefore, it can be difficult to disentangle the affinity of the agonist for the
      target from its efficacy in producing the ensuing conformational change. Efficacy
      depends on two factors: the intrinsic equilibrium between active and inactive
      states in the absence of agonist, and the energy contributed by the agonist as a
      result of the relative affinities of agonist for the active and inactive states.
      These difficulties are particularly frustrating when the goal is to determine the
      role(s) that particular residues in a target protein have in shaping the overall
      efficacy of a drug: how is it possible to unambiguously distinguish a role in
      determining intrinsic efficacy from one in determining relative affinity? This
      perspective highlights a research article in this issue (p. 351) that
      demonstrates a quantitative approach to the resolution of this problem in the
      case of activation of the muscle nicotinic receptor. This elegant (if demanding)
      approach involves determining, separately, the consequences of specific mutations
      on gating in the unliganded and liganded states.

PMID- 21173043
TI  - Quantitative analysis of six heterocyclic aromatic amines in mainstream cigarette
      smoke condensate using isotope dilution liquid chromatography-electrospray
      ionization tandem mass spectrometry.
AB  - INTRODUCTION: Heterocyclic aromatic amines (HAAs) represent an important class of
      carcinogens in mainstream cigarette smoke. Accurate HAA quantification is
      challenging because of their relative low abundances and numerous chemical
      interferences that arise naturally from thousands of the constituents present in
      cigarette smoke. We have developed and validated a straightforward high
      throughput method to quantify HAA levels in mainstream cigarette smoke and
      demonstrated the applicability by analyzing select research and domestic
      cigarette brands. METHODS: Machine-smoked cigarette condensate collected under
      both standard and intensive smoking regimens was examined. Mainstream smoke
      particulate from individual cigarettes trapped on a glass fiber filter pad was
      spiked with an appropriate internal standard solution and subsequently solvent
      extracted. The extract was quantitatively analyzed by high-performance liquid
      chromatography and tandem mass spectrometry. RESULTS: Method validation data
      showed excellent accuracy, reproducibility and high throughput; it is suitable
      for the routine analysis of HAAs in cigarette smoke condensate delivered under a
      wide of differing smoking conditions. The smoking machine deliveries of HAAs are
      strongly influenced by cigarettes' physical design, filler blend, and smoking
      regimen. CONCLUSIONS: A quick and accurate method has been developed for the
      analysis of 6 HAAs in mainstream cigarette smoke condensate. Results provided a
      good mean to access the ranges of HAAs in commercial products and evaluate the
      relative contribution of cigarette design, filler blend, and smoking regimen on
      delivery. Such data are vital in helping provide exposure ranges for potential
      human exposure estimates.

PMID- 21173051
TI  - Republished: Which antibody and which cancer in which paraneoplastic syndromes?
AB  - Paraneoplastic neurological syndromes can be associated with the presence of
      onconeural antibodies. These antibodies are the result of an immune response
      against a tumour that is ectopically expressing a neuronal antigen. The
      'classical' onconeural antibodies (anti-Hu, Yo, Ma2, CRMP-5, amphiphysin and Ri)
      are directed against intracellular antigens and are strongly associated with
      underlying malignancy. By contrast, onconeural antibodies directed against cell
      surface antigens (eg, anti-NMDA, VGKC, AChR) have a weaker tumour association.
      This article gives a practical overview of the tumour associations, and the
      neurological associations, of the onconeural antibodies. There is also guidance
      on how to investigate occult malignancy in antibody positive cases.

PMID- 21173052
TI  - Republished paper: The quest to eliminate intrathecal vincristine errors: a 40
      year journey.
AB  - BACKGROUND: Intrathecal administration of vincristine is a rare event but
      catastrophic for the patient, family and clinical team involved. Analysis of this
      source of harm shows it to be a classic systems error which has proved
      intractable for nearly 40 years. Failure to learn from history, communicate
      safety solutions nationally and internationally, create safety agencies which
      effectively and reliably prevent adverse events, conduct investigations and
      enquiries which fully reveals how to mitigate system error, develop robust
      physical design solutions to prevent harm to patients, make effective solutions
      universal and preparing for the unexpected are all major challenges. CONCLUSIONS:
      The elimination of rare yet catastrophic errors like this remains one of the
      tests of whether we can make healthcare safer. In this paper, we discuss why
      effective learning has been so slow and illustrate lessons for other fields of
      patient safety.

PMID- 21173053
TI  - Combined pneumothorax and pneumoperitoneum following blunt trauma: an insidious
      diagnostic and therapeutic dilemma.

PMID- 21173054
TI  - Why do men have nipples?

PMID- 21173055
TI  - Development of antibiotic marker-free creeping bentgrass resistance against
      herbicides.
AB  - Herbicide-resistant creeping bentgrass plants (Agrostis stolonifera L.) without
      antibiotic-resistant markers were produced by Agrobacterium-mediated
      transformation. Embryogenic callus tissues were infected with Agrobacterium
      tumefaciens EHA105, harboring the bar and the CP4-EPSPS genes for bialaphos and
      glyphosate resistance. Phosphinothricin-resistant calli and plants were selected.
      Soil-grown plants were obtained at 14-16 weeks after transformation. Genetic
      transformation of the selected, regenerated plants was validated by PCR. Southern
      blot analysis revealed that at least one copy of the transgene was integrated
      into the genome of the transgenic plants. Transgene expression was confirmed by
      Northern blot. CP4-EPSPS protein was detected by ELISA. Transgenic plants
      remained green and healthy when sprayed with Basta, containing 0.5% glufosinate
      ammonium or glyphosate. The optimized Agrobacterium-mediated transformation
      method resulted in an average of 9.4% transgenic plants. The results of the
      present study suggest that the optimized marker-free technique could be used as
      an effective and reliable method for routine transformation, which may facilitate
      the development of varieties of new antibiotic-free grass species.

PMID- 21173056
TI  - Quercetin induces apoptosis by activating caspase-3 and regulating Bcl-2 and
      cyclooxygenase-2 pathways in human HL-60 cells.
AB  - Quercetin is one of the naturally occurring dietary flavonol compounds. It is
      present abundantly in plants and has chemopreventive and anticancer effects. To
      investigate its anticancer mechanism, we examined the activity of quercetin
      against acute leukemia cell line, HL-60. Our results showed that quercetin
      inhibited cell proliferation and induced apoptosis in a time- and dose-dependent
      manner. Furthermore, quercetin down-regulated the expression of anti-apoptosis
      protein Bcl-2 and up-regulated the expression of pro-apoptosis protein Bax.
      Caspase-3 was also activated by quercetin, which started a caspase-3-depended
      mitochodrial pathway to induce apoptosis. It was also found that quercetin
      inhibited the expression of the cycloocygenase-2 (Cox-2) mRNA and Cox-2 protein.
      Taken together, these findings suggested that quercetin induces apoptosis in a
      caspase-3-dependent pathway by inhibiting Cox-2 expression and regulates the
      expression of downstream apoptotic components, including Bcl-2 and Bax. Quercetin
      can be a potent and promising medicine which might be safely used in leukemia
      therapy.

PMID- 21173057
TI  - Poliovirus 2A(pro) induces the nucleic translocation of poliovirus 3CD and 3C'
      proteins.
AB  - Poliovirus genomic RNA replication, protein translation, and virion assembly are
      performed in the cytoplasm of host cells. However, this does not mean that there
      is no relationship between poliovirus infection and the cellular nucleus. In this
      study, recombinant fluorescence-tagged poliovirus 3CD and 3C' proteins were shown
      to be expressed mainly in the cytoplasm of Vero cells in the absence of other
      viral proteins. However, upon poliovirus infection, many of these proteins
      redistributed to the nucleus, as well as to the cytoplasm. A series of
      transfection experiments revealed that the poliovirus 2A(pro) was responsible for
      the same redistribution of 3CD and 3C' proteins to the nucleus. Furthermore, a
      mutant 2A(pro) protein lacking protease activity abrogated this effect. The
      poliovirus 2A(pro) protein was also found to co-localize with the Nup153 protein,
      a component of the nuclear pore complexes on the nuclear envelope. These data
      provide further evidence that there are intrinsic interactions between poliovirus
      proteins and the cell nucleus, despite that many processes in the poliovirus
      replication cycle occur in the cytoplasm.

PMID- 21173058
TI  - Stability analysis of liver cancer-related microRNAs.
AB  - MicroRNAs (miRNAs) are non-coding, single-stranded RNAs of approximately 22 nt
      and constitute a novel class of gene regulators that are found in both plants and
      animals. Several studies have demonstrated that serum miRNAs could serve as
      potential biomarkers for the detection of various cancers and other diseases. A
      few documents regarding the stability of liver cancer-related miRNAs in serum are
      available. A systemic analysis of the stability of miRNA in serum is quite
      necessary. The purpose of this study was to evaluate the stability of miRNAs from
      three different sources, cultured liver cancer Huh-7 cell line, clinical liver
      cancer, and serum under different experimental conditions, including different
      temperature, time duration, pH values, RNase A digestion, DNase I digestion, and
      various freeze-thaw cycles. The qRT-PCR analysis demonstrated that liver cancer
      related miRNAs were detectable under each of test conditions, indicating that
      miRNAs were extremely stable and resistant to destruction and degradation under
      harsh environmental conditions. However, ribosomal RNA was fragile and easily
      degraded by demonstrating sharp decrease of relative expression under the non
      physiological test conditions. We also established a robust procedure for serum
      RNA extraction, which is greatly important not only for the miRNA profiling
      studies but also for the disease prognosis based on abnormal miRNA expression.

PMID- 21173059
TI  - British Columbia revamps process for determining drug coverage.

PMID- 21173060
TI  - Infectious diarrhea: when to test and when to treat.

PMID- 21173062
TI  - Fracture-risk calculators: Has their time come?

PMID- 21173063
TI  - Germany moves to lower drug prices.

PMID- 21173064
TI  - WHO moves to classify traditional medicines.

PMID- 21173065
TI  - Lower gastrointestinal bleeding caused by stercoral ulcer.

PMID- 21173066
TI  - Infectious risks in family doctors' offices.

PMID- 21173067
TI  - Move if u wanna: Obama and the weight loss nudge.

PMID- 21173068
TI  - Health Canada "passes the buck" on diabetes drug, researcher charges.

PMID- 21173069
TI  - Independent external validation of nomograms for predicting risk of low-trauma
      fracture and hip fracture.
AB  - BACKGROUND: A set of nomograms based on the Dubbo Osteoporosis Epidemiology Study
      predicts the five- and ten-year absolute risk of fracture using age, bone mineral
      density and history of falls and low-trauma fracture. We assessed the
      discrimination and calibration of these nomograms among participants in the
      Canadian Multicentre Osteoporosis Study. METHODS: We included participants aged
      55-95 years for whom bone mineral density measurement data and at least one year
      of follow-up data were available. Self-reported incident fractures were
      identified by yearly postal questionnaire or interview (years 3, 5 and 10). We
      included low-trauma fractures before year 10, except those of the skull, face,
      hands, ankles and feet. We used a Cox proportional hazards model. RESULTS: Among
      4152 women, there were 583 fractures, with a mean follow-up time of 8.6 years.
      Among 1606 men, there were 116 fractures, with a mean follow-up time of 8.3
      years. Increasing age, lower bone mineral density, prior fracture and prior falls
      were associated with increased risk of fracture. For low-trauma fractures, the
      concordance between predicted risk and fracture events (Harrell C) was 0.69 among
      women and 0.70 among men. For hip fractures, the concordance was 0.80 among women
      and 0.85 among men. The observed fracture risk was similar to the predicted risk
      in all quintiles of risk except the highest quintile of women, where it was
      lower. The net reclassification index (19.2%, 95% confidence interval [CI] 6.3%
      to 32.2%), favours the Dubbo nomogram over the current Canadian guidelines for
      men. INTERPRETATION: The published nomograms provide good fracture-risk
      discrimination in a representative sample of the Canadian population.

PMID- 21173070
TI  - Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta
      analysis.
AB  - BACKGROUND: Observational studies and randomized controlled trials have yielded
      inconsistent findings about the association between the use of acid-suppressive
      drugs and the risk of pneumonia. We performed a systematic review and meta
      analysis to summarize this association. METHODS: We searched three electronic
      databases (MEDLINE [PubMed], Embase and the Cochrane Library) from inception to
      Aug. 28, 2009. Two evaluators independently extracted data. Because of
      heterogeneity, we used random-effects meta-analysis to obtain pooled estimates of
      effect. RESULTS: We identified 31 studies: five case-control studies, three
      cohort studies and 23 randomized controlled trials. A meta-analysis of the eight
      observational studies showed that the overall risk of pneumonia was higher among
      people using proton pump inhibitors (adjusted odds ratio [OR] 1.27, 95%
      confidence interval [CI] 1.11-1.46, I(2) 90.5%) and histamine(2) receptor
      antagonists (adjusted OR 1.22, 95% CI 1.09-1.36, I(2) 0.0%). In the randomized
      controlled trials, use of histamine(2) receptor antagonists was associated with
      an elevated risk of hospital-acquired pneumonia (relative risk 1.22, 95% CI 1.01
      1.48, I(2) 30.6%). INTERPRETATION: Use of a proton pump inhibitor or histamine(2)
      receptor antagonist may be associated with an increased risk of both community-
      and hospital-acquired pneumonia. Given these potential adverse effects,
      clinicians should use caution in prescribing acid-suppressive drugs for patients
      at risk.

PMID- 21173071
TI  - Human ZP4 is not sufficient for taxon-specific sperm recognition of the zona
      pellucida in transgenic mice.
AB  - The molecular basis of human fertilization remains enigmatic. Mouse models are
      often used to study sperm-egg recognition, but the mouse zona pellucida
      surrounding ovulated eggs contains three proteins (ZP1, ZP2, and ZP3) whereas the
      human zona contains four (ZP1, ZP2, ZP3, and ZP4). Human sperm are fastidious and
      recognize human but not mouse eggs. Transgenic mouse lines were established to
      ascertain whether human ZP4 is the sole determinant of human sperm binding. Human
      ZP4 expressed in transgenic mice had a molecular mass similar to the range of
      native protein isoforms and was incorporated into the extracellular zona matrix.
      Transgenic females were fertile with normal litter sizes. Mouse sperm readily
      recognized transgenic ovulated eggs, but human sperm did not. We conclude that
      human ZP4 is not sufficient to support human sperm binding to the zona pellucida
      in transgenic mice and that other zona proteins may be needed for human gamete
      recognition.

PMID- 21173072
TI  - Adrenomedullin increases ciliary beat frequency and decreases muscular
      contraction in the rat oviduct.
AB  - Our laboratory previously showed that oviduct produced the greatest amount of
      adrenomedullin (ADM) in the rat female reproductive tract. The aim of this study
      is to investigate the changes in ADM levels resulting from the contact between
      the sperm and the oviduct and the possible roles of ADM in ciliary beating and
      oviductal contractility. Oviducts from Sprague-Dawley rats removed at pre- and
      post-ovulatory stages were cut open longitudinally and treated with ADM and/or
      receptor blockers before ciliary beat frequency (CBF) was measured. The effects
      of sperm on ADM production and CBF in the oviduct were also determined. The
      contraction of the oviduct after treatment with ADM and receptor antagonists was
      measured using the organ-bath technique. The results showed that ADM increased
      the CBF in rat oviduct and this stimulating effect was blocked by the calcitonin
      gene-related peptide (CGRP) receptor antagonist, hCGRP(8-37). CBF was lower in
      post-ovulatory than pre-ovulatory oviducts. The presence of sperm in the oviduct
      increased both the ADM level and CBF. ADM treatment was shown to inhibit the
      contractility of the oviduct by lowering the basal tone and decreasing the
      contraction amplitude. The ADM receptor antagonist, hADM(22-52), was effective in
      counteracting the relaxation effect of ADM in the oviduct. All in all, these
      results indicate that ADM may play a crucial role in transporting the
      gametes/embryos by regulating ciliary beating and muscular contraction.

PMID- 21173073
TI  - Regulation of visceral sympathetic tone by A5 noradrenergic neurons in rodents.
AB  - The ventrolateral pons contains the A5 group of noradrenergic neurons which
      regulate the circulation and probably breathing. The present experiments were
      designed to identify these neurons definitively in vivo, to examine their
      response to chemoreceptor stimuli (carotid body stimulation and changes in brain
      pH) and to determine their effects on sympathetic outflow. Bulbospinal A5
      neurons, identified by juxtacellular labelling in anaesthetized rats, had a slow
      regular discharge, were vigorously activated by peripheral chemoreceptor
      stimulation with cyanide, but only mildly activated by hyperoxic hypercapnia
      (central chemoreceptor stimulation). The caudal end of the A5 region also
      contained neurons with properties reminiscent of retrotrapezoid neurons. These
      cells lacked a spinal axon and were characterized by a robust response to CO2.
      The pH sensitivity of A5 neurons, examined in brain slices from neonatal
      (postnatal days 6-10) tyrosine hydroxylase (TH)-GFP transgenic mice, was about 10
      times smaller than that of similarly recorded retrotrapezoid neurons. Selective
      stimulation of the A5 neurons in rats using channelrhodopsin optogenetics (A5 TH
      neurons represented 66% of transfected cells) produced fivefold greater
      activation of the renal nerve than the lumbar sympathetic chain. In summary,
      adult A5 noradrenergic neurons are vigorously activated by carotid body
      stimulation. This effect presumably contributes to the increase in visceral
      sympathetic nerve activity elicited by acute hypoxia. A5 neurons respond weakly
      to hypercapnia in vivo or to changes in pH in slices suggesting that their
      ability to sense local variations in brain pH or Pco2 is limited.

PMID- 21173075
TI  - Requirements for synaptically evoked plateau potentials in relay cells of the
      dorsal lateral geniculate nucleus of the mouse.
AB  - In developing cells of the mouse dorsal lateral geniculate nucleus (dLGN),
      synaptic responses evoked by optic tract (OT) stimulation give rise to long
      lasting, high-amplitude depolarizations known as plateau potentials. These events
      are mediated by L-type Ca2+ channels and occur during early postnatal life, a
      time when retinogeniculate connections are remodelling. To better understand the
      relationship between L-type activity and dLGN development we used an in vitro
      thalamic slice preparation which preserves the retinal connections and intrinsic
      circuitry in dLGN and examined how synaptic responses evoked by OT stimulation
      lead to the activation of plateau potentials. By varying the strength and
      temporal frequency of OT stimulation we identified at least three factors that
      contribute to the developmental regulation of plateau activity: the degree of
      retinal convergence, the temporal pattern of retinal stimulation and the
      emergence of feed-forward inhibition. Before natural eye opening (postnatal day
      14), the excitatory synaptic responses of relay cells receiving multiple retinal
      inputs summated in both the spatial and temporal domains to produce
      depolarizations sufficient to activate L-type activity. After eye opening, when
      inhibitory responses are fully developed, plateau activity was rarely evoked even
      with high temporal rates of OT stimulation. When the bulk of this inhibition was
      blocked by bath application of bicuculline, the incidence of plateau activity
      increased significantly. We also made use of a transgenic mouse that lacks the
      beta3 subunit of the L-type Ca2+ channel. These mutants have far fewer membrane
      bound Ca2+ channels and attenuated L-type activity. In beta3 nulls, L-type
      plateau activity was rarely observed even at young ages when plateau activity
      prevails. Thus, in addition to the changing patterns of synaptic connectivity and
      retinal activity, the expression of L-type Ca2+ channels is a requisite component
      in the manifestation of plateau activity.

PMID- 21173074
TI  - T-type calcium channels and vascular function: the new kid on the block?
AB  - While L-type voltage-dependent calcium channels have long been considered the
      predominant source of calcium for myogenic constriction, recent studies of both
      cerebral and systemic circulations have provided evidence for the prominent
      expression of other members of the voltage-dependent calcium channel family, in
      particular the low voltage activated T-type channels. Although physiological
      studies have not supported the involvement of a classical low voltage activated,
      T-type channel in vascular function, evidence is accumulating that points to the
      involvement of a non-L-type, high voltage activated channel with sensitivity to T
      type channel antagonists. We propose that this may arise due to expression of a T
      type channel splice variant with unique biophysical characteristics resulting in
      a more depolarised profile. Expression of these channels in smooth muscle cells
      would broaden the voltage range over which sustained calcium influx occurs, while
      expression of T-type channels in endothelial cells could provide a feedback
      mechanism to prevent excessive vasoconstriction. Perturbation of this balance
      during pathophysiological conditions by upregulation of channel expression and
      endothelial dysfunction could contribute to vasospastic conditions and therapy
      refractory hypertension.

PMID- 21173076
TI  - Progesterone enhances adrenergic control of skin blood flow in women with high
      but not low orthostatic tolerance.
AB  - Women are more susceptible to orthostatic intolerance. Peripheral alpha
      adrenergic responsiveness is important in orthostasis and is lower in women
      compared to men, and is modulated by female sex hormones. We tested the
      hypothesis that oestradiol attenuates peripheral cutaneous adrenergic responses
      in women with low orthostatic tolerance (LT), whereas progesterone enhances
      adrenergic responses in women with high orthostatic tolerance (HT). After
      completing a maximal lower body negative pressure test to determine level of
      orthostatic tolerance (cumulative stress index, CSI), women self administered a
      gonadotropin releasing hormone (GnRH) antagonist for 16 days to suppress
      endogenous sex hormone production. Oestradiol (E2, 0.2 mg day-1, patch; days 4
      16), and progesterone (P4, 200 mg day-1, oral; days 12-16) were administered.
      Skin blood flow responses to graded intradermal microdialysis infusions of
      noradrenaline (NA) were measured during GnRH antagonist, E2, and E2+P4, in eight
      HT (s.e.m. = 22 +/- 1 years, CSI -871 +/- 86 mmHg min) and eight LT (21 +/- 1
      years, CSI -397 +/- 65 mmHg min) women. In separate probes, NA was infused alone,
      and co-infused with the nitric oxide synthase inhibitor NG-monomethyl-l-arginine
      (l-NMMA, 10 mm), the non-selective cyclooxygenase inhibitor ketorolac
      tromethamine (Keto, 10 mm), and combined l-NMMA + Keto (10 mm each). Progesterone
      administration enhanced adrenergic responses in HT women (logEC50 GnRH -4.02 +/-
      0.39, E2+P4 -5.18 +/- 0.31, P < 0.05); this response was reversed with Keto
      (E2+P4 logEC50 NA+Keto -3.82 +/- 0.35, P < 0.05). In contrast, no change in
      adrenergic responsiveness occurred in LT women during any hormone condition.
      These data indicate differential regulation of cutaneous adrenergic responses by
      progesterone via the cyclooxygenase pathway in women with high and low
      orthostatic tolerance.

PMID- 21173077
TI  - Retinoic acid stimulation of VEGF secretion from human endometrial stromal cells
      is mediated by production of reactive oxygen species.
AB  - It is widely accepted that vascular endothelial growth factor (VEGF) is involved
      in angiogenic functions that are necessary for successful embryonic implantation.
      We have shown that retinoic acid (RA), which is known to play a necessary role in
      early events in pregnancy, can combine with transcriptional activators of VEGF
      (e.g. TPA, TGF-beta, IL-1beta) to rapidly induce VEGF secretion from human
      endometrial stromal cells through a translational mechanism of action. We have
      now determined that this stimulation of VEGF by RA is mediated through an
      increased production of cellular reactive oxygen species (ROS). Results indicated
      that RA, but not TPA or TGF-beta, directly increases ROS production in
      endometrial stromal cells and that the co-stimulating activity of RA on VEGF
      secretion can be mimicked by direct addition of H2O2. Importantly, co-treatment
      of RA with TPA or TGF-beta further stimulated ROS production in a fashion that
      positively correlated with levels of VEGF secretion. The antioxidants N
      acetylcysteine and glutathione monoethyl ester inhibited both RA + TPA and RA +
      TGF-beta-stimulated secretion of VEGF, as well as RA-induced ROS production.
      Treatment of cells with RA resulted in a shift in the glutathione (GSH) redox
      potential to a more oxidative state, suggesting that the transduction pathway
      leading to increased VEGF secretion is at least partially mediated through the
      antioxidant capacity of GSH couples. The specificity of this action on GSH
      sensitive signalling pathways is suggested by the determination that RA had no
      effect on the redox potential of thioredoxin. Together, these findings predict a
      redox-mediated mechanism for retinoid regulation of localized VEGF secretion in
      the human endometrium that may be necessary for the successful establishment of
      pregnancy.

PMID- 21173078
TI  - Angiotensin1-9 antagonises pro-hypertrophic signalling in cardiomyocytes via the
      angiotensin type 2 receptor.
AB  - The renin-angiotensin system (RAS) regulates blood pressure mainly via the
      actions of angiotensin (Ang)II, generated via angiotensin converting enzyme
      (ACE). The ACE homologue ACE2 metabolises AngII to Ang1-7, decreasing AngII and
      increasing Ang1-7, which counteracts AngII activity via the Mas receptor.
      However, ACE2 also converts AngI to Ang1-9, a poorly characterised peptide which
      can be further converted to Ang1-7 via ACE. Ang1-9 stimulates bradykinin release
      in endothelium and has antihypertrophic actions in the heart, attributed to its
      being a competitive inhibitor of ACE, leading to decreased AngII, rather than
      increased Ang1-7. To date no direct receptor-mediated effects of Ang1-9 have been
      described. To further understand the role of Ang1-9 in RAS function we assessed
      its action in cardiomyocyte hypertrophy in rat neonatal H9c2 and primary adult
      rabbit left ventricular cardiomyocytes, compared to Ang1-7. Cardiomyocyte
      hypertrophy was stimulated with AngII or vasopressin, significantly increasing
      cell size by approximately 1.2-fold (P < 0.05) as well as stimulating expression
      of the hypertrophy gene markers atrial natriuretic peptide, brain natriuretic
      peptide, beta-myosin heavy chain and myosin light chain (2- to 5-fold, P < 0.05).
      Both Ang1-9 and Ang1-7 were able to block hypertrophy induced by either agonist
      (control, 186.4 MUm; AngII, 232.8 MUm; AngII+Ang1-7, 198.3 MUm; AngII+Ang1-9,
      195.9 MUm; P < 0.05). The effects of Ang1-9 were not inhibited by captopril,
      supporting previous evidence that Ang1-9 acts independently of Ang1-7. Next, we
      investigated receptor signalling via angiotensin type 1 and type 2 receptors
      (AT1R, AT2R) and Mas. The AT1R antagonist losartan blocked AngII-induced, but not
      vasopressin-induced, hypertrophy. Losartan did not block the antihypertrophic
      effects of Ang1-9, or Ang1-7 on vasopressin-stimulated cardiomyocytes. The Mas
      antagonist A779 efficiently blocked the antihypertrophic effects of Ang1-7,
      without affecting Ang1-9. Furthermore, Ang1-7 activity was also inhibited in the
      presence of the bradykinin type 2 receptor antagonist HOE140, without affecting
      Ang1-9. Moreover, we observed that the AT2R antagonist PD123,319 abolished the
      antihypertrophic effects of Ang1-9, without affecting Ang1-7, suggesting Ang1-9
      signals via the AT2R. Radioligand binding assays demonstrated that Ang1-9 was
      able to bind the AT2R (pKi = 6.28 +/- 0.1). In summary, we ascribe a direct
      biological role for Ang1-9 acting via the AT2R. This has implications for RAS
      function and identifying new therapeutic targets in cardiovascular disease.

PMID- 21173080
TI  - Emerging concepts for the role of TRP channels in the cardiovascular system.
AB  - The transient receptor potential (TRP) family of ion channels is a large family
      of cation selective ion channels, which are expressed and functional in a variety
      of tissues. In this review we focus on the most recent results detailing the role
      of TRP channels in the cardiovascular system. The presented results underscore
      the role of TRP channels in cardiomyocytes, smooth cells and endothelium, and in
      disease states such as hypertension, cardiac conduction block and cardiac
      hypertrophy.

PMID- 21173079
TI  - A functional role for the 'fibroblast-like cells' in gastrointestinal smooth
      muscles.
AB  - Smooth muscles, as in the gastrointestinal tract, are composed of several types
      of cells. Gastrointestinal muscles contain smooth muscle cells, enteric neurons,
      glial cells, immune cells, and various classes of interstitial cells. One type of
      interstitial cell, referred to as 'fibroblast-like cells' by morphologists, are
      common, but their function is unknown. These cells are found near the terminals
      of enteric motor neurons, suggesting they could have a role in generating neural
      responses that help control gastrointestinal movements. We used a novel mouse
      with bright green fluorescent protein expressed specifically in the fibroblast
      like cells to help us identify these cells in the mixture of cells obtained when
      whole muscles are dispersed with enzymes. We isolated these cells and found they
      respond to a major class of inhibitory neurotransmitters - purines. We
      characterized these responses, and our results provide a new hypothesis about the
      role of fibroblast-like cells in smooth muscle tissues.

PMID- 21173082
TI  - Requirement for CB1 but not GABAB receptors in the cholecystokinin mediated
      inhibition of GABA release from cholecystokinin expressing basket cells.
AB  - Cholecystokinin (CCK) is an abundant neuropeptide involved in normal behaviour
      and pathophysiological conditions. Recently, CCK was shown to act as a molecular
      switch for perisomatic inhibition in the hippocampus, by directly depolarizing
      parvalbumin expressing (PV+) basket cells while indirectly depressing GABA
      release from CCK expressing (CCK+) basket cells. However, whether these two CCK
      mediated effects are causally related is controversial, with one hypothesis
      proposing that the CCK-induced firing of PV+ basket cells increases the release
      of GABA, which, in turn, heterosynaptically inhibits GABA release from
      neighbouring CCK+ basket cell terminals through presynaptic GABAB receptors. Our
      present data from paired recording experiments from presynaptic basket cells and
      postsynaptic CA1 pyramidal cells in acute rat brain slices show that the P/Q Ca2+
      channel antagonist agatoxin TK (250 nm) abolished GABA release from PV+ basket
      cells, but it had no effect on the CCK-induced depression of GABA release from
      CCK+ basket cells. Furthermore, CCK decreased GABA release from CCK+ basket cells
      even in the presence of the GABAB receptor antagonist CGP55845 (2 MUm). In
      contrast, cannabinoid type-1 (CB1) receptor blockade with AM251 (10 MUm)
      prevented the action of CCK on GABA release both from CCK+ basket cells and
      dendritically projecting, CCK+ Schaffer collateral-associated interneurons. These
      results demonstrate that CCK-mediated inhibition of GABA release from CCK+ cells
      requires no cross-talk between PV+ and CCK+ synapses, but that it critically
      depends on CB1 receptor-mediated endocannabinoid signalling at both perisomatic
      and dendritic inputs.

PMID- 21173081
TI  - Testosterone is involved in mediating the effects of prenatal stress in male
      guinea pig offspring.
AB  - Studies in humans have demonstrated a link between stress during pregnancy and
      altered behaviour and stress reactivity in children. In guinea pigs, we have
      previously shown that a short period of maternal stress during gestation leads to
      increased anxiety, elevated basal cortisol levels and decreased testosterone
      levels in adult males. We hypothesized that restoring testosterone to normal
      levels in the adult males born to prenatally stressed mothers would reverse the
      changes in behaviours and endocrine function. We found differences in attention
      and anxiety-related behaviours and basal stress endocrine activity between the
      prenatally stressed and control males. Administration of testosterone reversed
      the behavioural differences in the prenatally stressed offspring. There was,
      however, little effect of postnatal testosterone administration on stress-related
      endocrine activity. This study provides new information to begin to address the
      mechanism underlying the interplay between prenatal stress, gonadal steroids and
      postnatal behaviours.

PMID- 21173083
TI  - Etomidate and propofol inhibit the neurotransmitter release machinery at
      different sites.
AB  - The mechanism of general anaesthetic action is only partially understood.
      Facilitation of inhibitory GABAA receptors plays an important role in the action
      of most anaesthetics, but is thought to be especially relevant in the case of
      intravenous anaesthetics, like etomidate and propofol. Recent evidence suggests
      that anaesthetics also inhibit excitatory synaptic transmission via a presynaptic
      mechanism(s), but it has been difficult to determine whether these agents act on
      the neurotransmitter release machinery itself. In the present study we sought to
      determine whether the intravenous anaesthetics propofol and etomidate inhibit the
      release machinery. For these studies we used an experimental approach that
      directly regulated [Ca2+]i at neurotransmitter release sites, thereby bypassing
      anaesthetic effects on channels and receptors in order to allow anaesthetic
      effects on the neurotransmitter release machinery to be examined in isolation.
      The data show that clinically relevant concentrations of propofol and etomidate
      inhibited the neurotransmitter release machinery in neurosecretory cells and in
      cultured hippocampal neurons. md130A is a mutant form of syntaxin with a
      truncated C-terminus. Overexpressing md130A in PC12 cells completely eliminated
      the reduction in neurotransmitter release produced by propofol, without affecting
      release itself. In contrast, overexpressing md130A in PC12 cells had little or no
      effect on the response to etomidate. These results suggest that both propofol and
      etomidate inhibit neurotransmitter release by a direct interaction with SNAREs
      and/or SNARE-associated proteins but they do so at different sites.

PMID- 21173084
TI  - A small leak may sink a great ship but what does it do to the heart?

PMID- 21173085
TI  - Rippling the cortex with high-frequency (>100 Hz) alternating current
      stimulation.

PMID- 21173086
TI  - CICR takes centre stage in {beta}-cells: a cute cascade connects cAMP to CICR.

PMID- 21173088
TI  - Modulation of the central chemoreflex magnitude by the peripheral chemoreceptors:
      a hyperadditive effect or are we barking up the wrong tree?

PMID- 21173087
TI  - Physiological versus pathological cardiac electrical remodelling: potential basis
      and relevance to clinical management.

PMID- 21173089
TI  - Evaluation of an intervention program to increase immunization compliance among
      school children.
AB  - State immunization laws necessitate compliance for students enrolling in a public
      or private school system. In support of state laws, school nurses expend hours to
      achieve immunization compliance with school-age children. For the purpose of
      creating a more efficient system, researchers implemented an educational and
      incentive program in local elementary schools to increase tetanus, diphtheria,
      and acellular pertussis (Tdap) booster compliance rates. Students were instructed
      in regard to their immune systems, immunizations, and where to obtain
      immunizations. In addition, compliant students were entered into a drawing for an
      iPod Shuffle or a RipStick. In 2009, the compliance rate expanded from 4% to 57%
      during a 4-week intervention program. Notably, the Tdap immunization compliance
      rate in the previous year (2008) was 54%. Researchers concluded that the
      intervention did not improve compliance rates significantly.

PMID- 21173090
TI  - A growth status measurement pilot in four Calgary area schools: perceptions of
      grade 5 students and their parents.
AB  - Reliable measures of growth in children are necessary for planning and evaluating
      obesity prevention programs. Currently, measured growth data are unavailable in
      Calgary for school-age children. This single sample, cross-sectional study
      included Grade 5 students and their parents. Height and weight measurements of
      305 students (68% of those eligible) were taken in private in June 2007 and
      converted to Body Mass Index (BMI) categories. All but one student (99.7%)
      completed a questionnaire assessing perceptions of the measurement process.
      Parents received their child's growth data, an information package on healthy
      eating and active living, additional resources, and a questionnaire. A third of
      parents completed the questionnaire. Most students (94.1%) reported feeling "OK"
      or "Happy" about being measured. In addition, 93.2% of parents reported having
      "Low" or "Neutral" concerns about the measurement. Furthermore, 28.1% of
      responding parents reported seeking additional resources or considered making a
      lifestyle change for their family following the pilot. Measurement of students
      completed in private by nurses was acceptable to participants.

PMID- 21173091
TI  - We need more focus on social inequality in rehabilitation.

PMID- 21173094
TI  - A high-risk signature for patients with multiple myeloma established from the
      molecular classification of human myeloma cell lines.
AB  - BACKGROUND: Multiple myeloma is a plasma-cell tumor with heterogeneity in
      molecular abnormalities and treatment response. DESIGN AND METHODS: We have
      assessed whether human myeloma cell lines have kept patients' heterogeneity using
      Affymetrix gene expression profiling of 40 human myeloma cell lines obtained with
      or without IL6 addition and could provide a signature for stratification of
      patient risk. RESULTS: Human myeloma cell lines, especially those derived in the
      presence of IL6, displayed a heterogeneity that overlaps that of the patients
      with multiple myeloma. Human myeloma cell lines segregated into 6 groups marked
      by overexpression of MAF, MMSET, CCND1, FRZB with or without overexpression of
      cancer testis antigens (CTA). Cell lines of CTA/MAF and MAF groups have a
      translocation involving C-MAF or MAFB, cell lines of groups CCND1-1 and CCND1
      2like have a t(11;14) and cell lines of group MMSET have a t(4;14). The CTA/FRZB
      group comprises cell lines that had no or no recurrent 14q32 translocation.
      Expression of 248 genes accounted for human myeloma cell line molecular
      heterogeneity. Human myeloma cell line heterogeneity genes comprise genes with
      prognostic value for survival of patients making it possible to build a powerful
      prognostic score involving a total of 13 genes. CONCLUSIONS: Human myeloma cell
      lines derived in the presence of IL6 recapitulate the molecular diversity of
      multiple myeloma that made it possible to design, using human myeloma cell line
      heterogeneity genes, a high-risk signature for patients at diagnosis. We propose
      this classification to be used when addressing the physiopathology of multiple
      myeloma with human myeloma cell lines.

PMID- 21173095
TI  - Subcutaneous injections of low-dose veltuzumab (humanized anti-CD20 antibody) are
      safe and active in patients with indolent non-Hodgkin's lymphoma.
AB  - BACKGROUND: Subcutaneous injections of anti-CD20 antibodies may offer benefits to
      both patients and the healthcare system for treatment of B-cell malignancies.
      DESIGN AND METHODS: A pilot study was undertaken to evaluate the potential for
      subcutaneous dosing with 2(nd) generation anti-CD20 antibody veltuzumab in
      patients with CD20(+) indolent non-Hodgkin's lymphoma. Patients with previously
      untreated or relapsed disease received 4 doses of 80, 160, or 320 mg veltuzumab
      injected subcutaneously every two weeks. Responses were assessed by computed
      tomography scans, with other evaluations including adverse events, safety
      laboratories, B-cell blood levels, serum veltuzumab levels, and human anti
      veltuzumab antibody (HAHA) titers. RESULTS: Seventeen patients (14 follicular
      lymphoma; 13 stage III or IV disease; 5 treatment-naive) completed treatment with
      only occasional, mild-moderate, transient injection reactions and no other safety
      issues. Subcutaneous veltuzumab demonstrated a slow release pattern over several
      days, achieving a mean Cmax of 19, 25 and 63 MUg/mL at 80, 160, and 320 mg doses
      for a total of 4 administrations, respectively. Depletion of circulating B cells
      occurred after the first injection. The objective response rate (partial
      responses plus complete responses plus complete responses unconfirmed) was 47%
      (8/17) with a complete response/complete response unconfirmed rate of 24% (4/17);
      4 of 8 objective responses continued for 60 weeks or more. All serum samples
      evaluated for human anti-veltuzumab antibody were negative. CONCLUSIONS:
      Subcutaneous injections of low-dose veltuzumab are convenient, well tolerated,
      and capable of achieving sustained serum levels, B-cell depletion, and durable
      objective responses in indolent non-Hodgkin's lymphoma. (Clinicaltrials.gov
      identifier: NCT00546793).

PMID- 21173096
TI  - Participation of Mac-1, LFA-1 and VLA-4 integrins in the in vitro adhesion of
      sickle cell disease neutrophils to endothelial layers, and reversal of adhesion
      by simvastatin.
AB  - BACKGROUND: Pharmacological approaches to inhibit increased leukocyte adhesive
      interactions in sickle cell disease may represent important strategies for the
      prevention of vaso-occlusion in patients with this disorder. We investigated, in
      vitro, the adhesion molecules involved in endothelial-sickle cell disease
      neutrophil interactions and the effect of simvastatin on sickle cell disease
      neutrophil adhesion to tumor necrosis factor-alpha-activated endothelial
      monolayers (human umbilical vein endothelial cells), and neutrophil chemotaxis.
      DESIGN AND METHODS: Sickle cell disease patients in steady state and not on
      hydroxyurea were included in the study. Endothelial cells treated, or not, with
      tumor necrosis factor-alpha and simvastatin were used for neutrophil adhesion
      assays. Neutrophils treated with simvastatin were submitted to interleukin 8
      stimulated chemotaxis assays. RESULTS: Sickle cell disease neutrophils showed
      greater adhesion to endothelial cells than control neutrophils. Adhesion of
      control neutrophils to endothelial cells was mediated by Mac-1 under basal
      conditions and by the Mac-1 and LFA-1 integrins under inflammatory conditions. In
      contrast, adhesion of sickle cell disease neutrophils to endothelium, under both
      basal and tumor necrosis factor-alpha-stimulated conditions, was mediated by Mac
      1 and LFA-1 integrins and also by VLA-4. Under stimulated inflammatory
      conditions, simvastatin significantly reduced sickle cell disease neutrophil
      adhesion, and this effect was reversed by inhibition of nitric oxide synthase.
      Furthermore, intercellular adhesion molecule-1 expression was significantly
      abrogated on tumor necrosis factor-alpha-stimulated endothelium incubated with
      simvastatin, and statin treatment inhibited the interleukin-8-stimulated
      migration of both control and sickle cell disease neutrophils. CONCLUSIONS: The
      integrins Mac-1, LFA-1 and, interestingly, VLA-4 mediate the adhesion of sickle
      cell disease leukocytes to activated endothelial cell layers, in vitro. Our data
      indicate that simvastatin may be able to reduce endothelial activation and
      consequent leukocyte adhesion in this in vitro model; future experiments and
      clinical trials may determine whether simvastatin therapy could be employed in
      patients with sickle cell disease, with beneficial effects on vaso-occlusion.

PMID- 21173097
TI  - Inflammation and thrombosis in essential thrombocythemia and polycythemia vera:
      different role of C-reactive protein and pentraxin 3.
AB  - We tested the hypothesis that levels of pentraxin high sensitivity C-reactive
      protein and pentraxin 3 might be correlated with cardiovascular complications in
      patients with essential thrombocythemia and polycythemia vera. High sensitivity C
      reactive protein and pentraxin 3 were measured in 244 consecutive essential
      thrombocythemia and polycythemia vera patients in whom, after a median follow up
      of 5.3 years (range 0-24), 68 cardiovascular events were diagnosed. The highest C
      reactive protein tertile was compared with the lowest (>3 vs. <1 mg/L) and
      correlated with age (P=0.001), phenotype (polycythemia vera vs. essential
      thrombocythemia, P=0.006), cardiovascular risk factors (P=0.012) and JAK2V617F
      allele burden greater than 50% (P=0.003). Major thrombosis rate was higher in the
      highest C-reactive protein tertile (P=0.01) and lower at the highest pentraxin 3
      levels (P=0.045). These associations remained significant in multivariate
      analyses and indicate that blood levels of high sensitivity C-reactive protein
      and petraxin 3 independently and in opposite ways modulate the intrinsic risk of
      cardiovascular events in patients with myeloproliferative disorders.

PMID- 21173098
TI  - A time course of hepcidin response to iron challenge in patients with HFE and
      TFR2 hemochromatosis.
AB  - BACKGROUND: Inadequate hepcidin production leads to iron overload in nearly all
      types of hemochromatosis. We explored the acute response of hepcidin to iron
      challenge in 25 patients with HFE-hemochromatosis, in two with TFR2
      hemochromatosis and in 13 controls. Sixteen patients (10 C282Y/C282Y homozygotes,
      6 C282Y/H63D compound heterozygotes) had increased iron stores, while nine (6
      C282Y/C282Y homozygotes, 3 C282Y/H63D compound heterozygotes) were studied after
      phlebotomy-induced normalization of iron stores. DESIGN AND METHODS: We analyzed
      serum iron, transferrin saturation, and serum hepcidin by both enzyme-linked
      immunosorbent assay and mass-spectrometry at baseline, and 4, 8, 12 and 24 hours
      after a single 65-mg dose of oral iron. RESULTS: Serum iron and transferrin
      saturation significantly increased at 4 hours and returned to baseline values at
      8-12 hours in all groups, except in the iron-normalized patients who showed the
      highest and longest increase of both parameters. The level of hepcidin increased
      significantly at 4 hours and returned to baseline at 24 hours in controls and in
      the C282Y/H63D compound heterozygotes at diagnosis. The hepcidin response was
      smaller in C282Y-homozygotes than in controls, barely detectable in the patients
      with iron-depleted HFE-hemochromatosis and absent in those with TFR2
      hemochromatosis. Conclusions Our results are consistent with a scenario in which
      TFR2 plays a prominent and HFE a contributory role in the hepcidin response to a
      dose of oral iron. In iron-normalized patients with HFE hemochromatosis, both the
      low baseline hepcidin level and the weak response to iron contribute to
      hyperabsorption of iron.

PMID- 21173099
TI  - Clinical and genetic aspects of Bernard-Soulier syndrome: searching for
      genotype/phenotype correlations.
AB  - BACKGROUND: Bernard-Soulier syndrome is a severe bleeding disease due to a defect
      of GPIb/IX/V, a platelet complex that binds the von Willebrand factor. Due to the
      rarity of the disease, there are reports only on a few cases compromising any
      attempt to establish correlations between genotype and phenotype. In order to
      identify any associations, we describe the largest case series ever reported,
      which was evaluated systematically at the same center. DESIGN AND METHODS:
      Thirteen patients with the disease and seven obligate carriers were enrolled. We
      collected clinical aspects and determined platelet features, including number and
      size, expression of membrane glycoproteins, and ristocetin induced platelet
      aggregation. Mutations were identified by direct sequencing of the GP1BA, GP1BB,
      and GP9 genes and their effect was shown by molecular modeling analyses. RESULTS:
      Patients all had a moderate thrombocytopenia with giant platelets and a bleeding
      tendency whose severity varied among individuals. Consistent with expression
      levels of GPIbalpha always lower than 10% of control values, platelet aggregation
      was absent or severely reduced. Homozygous mutations were identified in the
      GP1BA, GP1BB and GP9 genes; six were novel alterations expected to destabilize
      the conformation of the respective protein. Except for obligate carriers of a GP9
      mutation with a reduced GPIb/IX/V expression and defective aggregation, all the
      other carriers had no obvious anomalies. CONCLUSIONS: Regardless of mutations
      identified, the patients' bleeding diathesis did not correlate with
      thrombocytopenia, which was always moderate, and platelet GPIbalpha expression,
      which was always severely impaired. Obligate carriers had features similar to
      controls though their GPIb/IX/V expression showed discrepancies. Aware of the
      limitations of our cohort, we cannot define any correlations. However, further
      investigations should be encouraged to better understand the causes of this rare
      and underestimated disease.

PMID- 21173101
TI  - A phase 1 dose-escalation study: safety, tolerability, and pharmacokinetics of
      FBS0701, a novel oral iron chelator for the treatment of transfusional iron
      overload.
AB  - BACKGROUND: There is still a clinical need for a well-tolerated and safe iron
      chelator for the treatment of transfusional iron overload. We describe the
      pharmacokinetic properties and safety data after 7 days of dosing of FBS0701, a
      novel oral, once-daily iron chelator. DESIGN AND METHODS: This phase 1b dose
      escalation study to assess the safety, tolerability, pharmacokinetics and
      pharmacodynamics of FBS0701, a novel oral iron chelator for the treatment of
      transfusional iron overload, was conducted in 16 adult patients with iron
      overloaded consequent to transfusions. FBS0701 was given daily for 7 days at
      doses up to 32 mg/kg and was well tolerated at all dose levels. RESULTS:
      Pharmacokinetics showed dose-proportionality. The maxium plasma concentration
      (C(max)) was reached within 60-90 minutes of dosing and the drug was rapidly
      distributed at the predicted therapeutic doses. The plasma elimination half-life
      (t(1/2)) was approximately 19 hours. There were no serious adverse events
      associated with the drug. Conclusions On the basis of these safety and
      pharmacokinetic data, FBS0701 warrants further clinical evaluation in patients
      with transfusional iron overload. (Clinicaltrials.gov identifier: NCT01186419).

PMID- 21173100
TI  - The role of the JAK2 GGCC haplotype and the TET2 gene in familial
      myeloproliferative neoplasms.
AB  - BACKGROUND: Myeloproliferative neoplasms constitute a group of diverse chronic
      myeloid malignancies that share pathogenic features such as acquired mutations in
      the JAK2, TET2, CBL and MPL genes. There are recent reports that a JAK2 gene
      haplotype (GGCC or 46/1) confers susceptibility to JAK2 mutation-positive
      myeloproliferative neoplasms. The aim of this study was to examine the role of
      the JAK2 GGCC haplotype and germline mutations of TET2, CBL and MPL in familial
      myeloproliferative neoplasms. DESIGN AND METHODS: We investigated patients with
      familial (n=88) or sporadic (n=684) myeloproliferative neoplasms, and a control
      population (n=203) from the same demographic area in Italy. Association analysis
      was performed using tagged single nucleotide polymorphisms (rs10974944 and
      rs12343867) of the JAK2 haplotype. Sequence analysis of TET2, CBL and MPL was
      conducted in the 88 patients with familial myeloproliferative neoplasms. RESULTS:
      Association analysis revealed no difference in haplotype frequency between
      familial and sporadic cases of myeloproliferative neoplasms (P=0.6529). No
      germline mutations in TET2, CBL or MPL that segregate with the disease phenotype
      were identified. As we observed variability in somatic mutations in the affected
      members of a pedigree with myeloproliferative neoplasms, we postulated that
      somatic mutagenesis is increased in familial myeloproliferative neoplasms.
      Accordingly, we compared the incidence of malignant disorders between sporadic
      and familial patients. Although the overall incidence of malignant disorders did
      not differ significantly between cases of familial and sporadic
      myeloproliferative neoplasms, malignancies were more frequent in patients with
      familial disease aged between 50 to 70 years (P=0.0198) than in patients in the
      same age range with sporadic myeloproliferative neoplasms. CONCLUSIONS: We
      conclude that the JAK2 GGCC haplotype and germline mutations of TET2, CBL or MPL
      do not explain familial clustering of myeloproliferative neoplasms. As we
      observed an increased frequency of malignant disorders in patients with familial
      myeloproliferative neoplasms, we hypothesize that the germline genetic lesions
      that underlie familial clustering of myeloproliferative neoplasms predispose to
      somatic mutagenesis that is not restricted to myeloid hematopoietic cells but
      cause an increase in overall carcinogenesis.

PMID- 21173102
TI  - Thymus-specific serine protease contributes to the diversification of the
      functional endogenous CD4 T cell receptor repertoire.
AB  - Thymus-specific serine protease (TSSP) is a novel protease that may contribute to
      the generation of the peptide repertoire presented by MHC class II molecules in
      the thymus. Although TSSP deficiency has no quantitative impact on the
      development of CD4 T cells expressing a polyclonal T cell receptor (TCR)
      repertoire, the development of CD4 T cells expressing the OTII and Marilyn
      transgenic TCRs is impaired in TSSP-deficient mice. In this study, we assess the
      role of TSSP in shaping the functional endogenous polyclonal CD4 T cell
      repertoire by analyzing the response of TSSP-deficient mice to several protein
      antigens (Ags). Although TSSP-deficient mice responded normally to most of the
      Ags tested, they responded poorly to hen egg lysozyme (HEL). The impaired CD4 T
      cell response of TSSP-deficient mice to HEL correlated with significant
      alteration of the dominant TCR-beta chain repertoire expressed by HEL-specific
      CD4 T cells, suggesting that TSSP is necessary for the intrathymic development of
      cells expressing these TCRs. Thus, TSSP contributes to the diversification of the
      functional endogenous CD4 T cell TCR repertoire in the thymus.

PMID- 21173103
TI  - Acquisition and presentation of follicular dendritic cell-bound antigen by lymph
      node-resident dendritic cells.
AB  - Follicular dendritic cells (DCs [FDCs]) are prominent stromal cell constituents
      of B cell follicles with the remarkable ability to retain complement-fixed
      antigens on their cell surface for extended periods of time. These retained
      immune complexes have long been known to provide the antigenic stimulus that
      drives antibody affinity maturation, but their role in cellular immunity has
      remained unclear. In this study, we show that FDC-retained antigens are
      continually sampled by lymph node-resident DCs for presentation to CD8 T cells.
      This novel pathway of antigen acquisition was detectable when FDCs were loaded
      with purified antigens bound into classical antigen-antibody immune complexes, as
      well as after pregnancy, when they are loaded physiologically with antigens
      associated with the complement-fixed microparticles released from the placenta
      into maternal blood. In both cases, ensuing antigen presentation was profoundly
      tolerogenic, as it induced T cell deletion even under inflammatory conditions.
      These results significantly broaden the scope of FDC function and suggest new
      ways that the complement system and persistent antigen presentation might
      influence T cell activation and the maintenance of peripheral immune tolerance.

PMID- 21173104
TI  - Cyclophilin A is an inflammatory mediator that promotes atherosclerosis in
      apolipoprotein E-deficient mice.
AB  - Cyclophilin A (CyPA; encoded by Ppia) is a ubiquitously expressed protein
      secreted in response to inflammatory stimuli. CyPA stimulates vascular smooth
      muscle cell migration and proliferation, endothelial cell adhesion molecule
      expression, and inflammatory cell chemotaxis. Given these activities, we
      hypothesized that CyPA would promote atherosclerosis. Apolipoprotein E-deficient
      (Apoe(-/-)) mice fed a high-cholesterol diet for 16 wk developed more severe
      atherosclerosis compared with Apoe(-/-)Ppia(-/-) mice. Moreover, CyPA deficiency
      was associated with decreased low-density lipoprotein uptake, VCAM-1 (vascular
      cell adhesion molecule 1) expression, apoptosis, and increased eNOS (endothelial
      nitric oxide synthase) expression. To understand the vascular role of CyPA in
      atherosclerosis development, bone marrow (BM) cell transplantation was performed.
      Atherosclerosis was greater in Apoe(-/-) mice compared with Apoe(-/-)Ppia(-/-)
      mice after reconstitution with CyPA(+/+) BM cells, indicating that vascular
      derived CyPA plays a crucial role in the progression of atherosclerosis. These
      data define a role for CyPA in atherosclerosis and suggest CyPA as a target for
      cardiovascular therapies.

PMID- 21173106
TI  - IL-27 promotes T cell-dependent colitis through multiple mechanisms.
AB  - Interleukin-27 (IL-27) is a cytokine known to have both proinflammatory and
      immunoregulatory functions. The latter appear to dominate in vivo, where IL-27
      suppresses TH17 responses and promotes the differentiation of Tr1 cells
      expressing interferon-gamma and IL-10 and lacking forkhead box P3 (Foxp3).
      Accordingly, IL-27 receptor alpha (Il27ra)-deficient mice suffer from exacerbated
      immune pathology when infected with various parasites or challenged with
      autoantigens. Because the role of IL-27 in human and experimental mouse colitis
      is controversial, we studied the consequences of Il27ra deletion in the mouse T
      cell transfer model of colitis and unexpectedly discovered a proinflammatory role
      of IL-27. Absence of Il27ra on transferred T cells resulted in diminished weight
      loss and reduced colonic inflammation. A greater fraction of transferred T cells
      assumed a Foxp3(+) phenotype in the absence of Il27ra, suggesting that IL-27
      functions to restrain regulatory T cell (T(reg)) development. Indeed, IL-27
      suppressed Foxp3 induction in vitro and in an ovalbumin-dependent tolerization
      model in vivo. Furthermore, effector cell proliferation and IFN-gamma production
      were reduced in the absence of Il27ra. Collectively, we describe a
      proinflammatory role of IL-27 in T cell-dependent intestinal inflammation and
      provide a rationale for targeting this cytokine in pathological situations that
      result from a breakdown in peripheral immune tolerance.

PMID- 21173105
TI  - Rapid expansion and long-term persistence of elevated NK cell numbers in humans
      infected with hantavirus.
AB  - Natural killer (NK) cells are known to mount a rapid response to several virus
      infections. In experimental models of acute viral infection, this response has
      been characterized by prompt NK cell activation and expansion followed by rapid
      contraction. In contrast to experimental model systems, much less is known about
      NK cell responses to acute viral infections in humans. We demonstrate that NK
      cells can rapidly expand and persist at highly elevated levels for >60 d after
      human hantavirus infection. A large part of the expanding NK cells expressed the
      activating receptor NKG2C and were functional in terms of expressing a licensing
      inhibitory killer cell immunoglobulin-like receptor (KIR) and ability to respond
      to target cell stimulation. These results demonstrate that NK cells can expand
      and remain elevated in numbers for a prolonged period of time in humans after a
      virus infection. In time, this response extends far beyond what is considered
      normal for an innate immune response.

PMID- 21173107
TI  - Microbiota-induced tertiary lymphoid tissues aggravate inflammatory disease in
      the absence of RORgamma t and LTi cells.
AB  - The programmed development of lymph nodes and Peyer's patches during ontogeny
      requires lymphoid tissue inducer (LTi) cells that express the nuclear hormone
      receptor RORgammat. After birth, LTi cells in the intestine cluster into
      cryptopatches, the precursors of isolated lymphoid follicles (ILFs), which are
      induced to form by symbiotic bacteria and maintain intestinal homeostasis. We
      show that in RORgammat-deficient mice, which lack LTi cells, programmed lymphoid
      tissues, ILFs, and Th17 cells, bacterial containment requires the generation of
      large numbers of tertiary lymphoid tissues (tLTs) through the activity of B
      cells. However, upon epithelial damage, these mice develop severe intestinal
      inflammation characterized by extensive recruitment of neutrophils and IgG(+) B
      cells, high expression of activation-induced deaminase in tLTs, and wasting
      disease. The pathology was prevented by antibiotic treatment or inhibition of
      lymphoid tissue formation and was significantly decreased by treatment with
      intravenous immunoglobulin G (IVIG). Our data show that intestinal
      immunodeficiency, such as an absence in RORgammat-mediated proinflammatory
      immunity, can be compensated by increased lymphoid tissue genesis. However, this
      comes at a high cost for the host and can lead to a deregulated B cell response
      and aggravated inflammatory pathology.

PMID- 21173108
TI  - Full disclosure in industry-sponsored laboratory medicine research studies:
      statement by the Consortium of Laboratory Medicine Journal Editors.

PMID- 21173109
TI  - Induced pluripotent stem cell-derived human platelets: one step closer to the
      clinic.
AB  - The era of induced pluripotent stem (iPS) cells carries with it the promise of
      virtually unlimited sources of autologous cells for regenerative medicine.
      However, efficiently differentiating iPS cells into fully functional mature cell
      types remains challenging. A new study reporting the formation of fully
      functional platelets from human iPS (hiPS) cells improves upon recent efforts to
      generate this enucleated cell type, which remains in high demand for therapeutic
      transfusions. Notably, their lack of nucleus renders platelets unable to retain
      the pluripotent or tumorigenic properties of iPS cells.

PMID- 21173110
TI  - Zfp521 controls bone mass by HDAC3-dependent attenuation of Runx2 activity.
AB  - Runx2 is indispensable for osteoblast lineage commitment and early
      differentiation but also blocks osteoblast maturation, thereby causing bone loss
      in Runx2 transgenic mice. Zinc finger protein 521 (Zfp521) antagonizes Runx2 in
      vivo. Eliminating one Zfp521 allele mitigates the cleidocranial dysplasia-like
      phenotype of newborn Runx2(+/-) mice, whereas overexpressing Zfp521 exacerbates
      it. Overexpressing Zfp521 also reverses the severe osteopenia of adult Runx2
      transgenic mice. Zfp521 binds to both Runx2 and histone deacetylase 3 (HDAC3),
      promotes their association, and antagonizes Runx2 transcriptional activity in an
      HDAC3-dependent manner. Mutating the Zfp521 zinc finger domains 6 and 26 reduces
      the binding of Zfp521 to Runx2 and inhibition of Runx2 activity. These data
      provide evidence that Zfp521 antagonizes Runx2 in vivo and thereby regulates two
      stages of osteoblast development, early during mesenchymal cell lineage
      commitment and later during osteoblast maturation. Thus, the balance and
      molecular interplay between Zfp521 and Runx2 contribute to the control of
      osteoblast differentiation, skeletal development, and bone homeostasis.

PMID- 21173111
TI  - Cdc42 localization and cell polarity depend on membrane traffic.
AB  - Cell polarity is essential for cell division, cell differentiation, and most
      differentiated cell functions including cell migration. The small G protein Cdc42
      controls cell polarity in a wide variety of cellular contexts. Although
      restricted localization of active Cdc42 seems to be important for its distinct
      functions, mechanisms responsible for the concentration of active Cdc42 at
      precise cortical sites are not fully understood. In this study, we show that
      during directed cell migration, Cdc42 accumulation at the cell leading edge
      relies on membrane traffic. Cdc42 and its exchange factor betaPIX localize to
      intracytosplasmic vesicles. Inhibition of Arf6-dependent membrane trafficking
      alters the dynamics of Cdc42-positive vesicles and abolishes the polarized
      recruitment of Cdc42 and betaPIX to the leading edge. Furthermore, we show that
      Arf6-dependent membrane dynamics is also required for polarized recruitment of
      Rac and the Par6-aPKC polarity complex and for cell polarization. Our results
      demonstrate influence of membrane dynamics on the localization and activation of
      Cdc42 and consequently on directed cell migration.

PMID- 21173113
TI  - HURP permits MTOC sorting for robust meiotic spindle bipolarity, similar to extra
      centrosome clustering in cancer cells.
AB  - In contrast to somatic cells, formation of acentriolar meiotic spindles relies on
      the organization of microtubules (MTs) and MT-organizing centers (MTOCs) into a
      stable bipolar structure. The underlying mechanisms are still unknown. We show
      that this process is impaired in hepatoma up-regulated protein (Hurp) knockout
      mice, which are viable but female sterile, showing defective oocyte divisions.
      HURP accumulates on interpolar MTs in the vicinity of chromosomes via Kinesin-5
      activity. By promoting MT stability in the spindle central domain, HURP allows
      efficient MTOC sorting into distinct poles, providing bipolarity establishment
      and maintenance. Our results support a new model for meiotic spindle assembly in
      which HURP ensures assembly of a central MT array, which serves as a scaffold for
      the genesis of a robust bipolar structure supporting efficient chromosome
      congression. Furthermore, HURP is also required for the clustering of extra
      centrosomes before division, arguing for a shared molecular requirement of MTOC
      sorting in mammalian meiosis and cancer cell division.

PMID- 21173112
TI  - Biphasic targeting and cleavage furrow ingression directed by the tail of a
      myosin II.
AB  - Cytokinesis in animal and fungal cells utilizes a contractile actomyosin ring
      (AMR). However, how myosin II is targeted to the division site and promotes AMR
      assembly, and how the AMR coordinates with membrane trafficking during
      cytokinesis, remains poorly understood. Here we show that Myo1 is a two-headed
      myosin II in Saccharomyces cerevisiae, and that Myo1 localizes to the division
      site via two distinct targeting signals in its tail that act sequentially during
      the cell cycle. Before cytokinesis, Myo1 localization depends on the septin
      binding protein Bni5. During cytokinesis, Myo1 localization depends on the IQGAP
      Iqg1. We also show that the Myo1 tail is sufficient for promoting the assembly of
      a "headless" AMR, which guides membrane deposition and extracellular matrix
      remodeling at the division site. Our study establishes a biphasic targeting
      mechanism for myosin II and highlights an underappreciated role of the AMR in
      cytokinesis beyond force generation.

PMID- 21173114
TI  - A computational model predicts Xenopus meiotic spindle organization.
AB  - The metaphase spindle is a dynamic bipolar structure crucial for proper
      chromosome segregation, but how microtubules (MTs) are organized within the
      bipolar architecture remains controversial. To explore MT organization along the
      pole-to-pole axis, we simulated meiotic spindle assembly in two dimensions using
      dynamic MTs, a MT cross-linking force, and a kinesin-5-like motor. The bipolar
      structures that form consist of antiparallel fluxing MTs, but spindle pole
      formation requires the addition of a NuMA-like minus-end cross-linker and
      directed transport of MT depolymerization activity toward minus ends. Dynamic
      instability and minus-end depolymerization generate realistic MT lifetimes and a
      truncated exponential MT length distribution. Keeping the number of MTs in the
      simulation constant, we explored the influence of two different MT nucleation
      pathways on spindle organization. When nucleation occurs throughout the spindle,
      the simulation quantitatively reproduces features of meiotic spindles assembled
      in Xenopus egg extracts.

PMID- 21173115
TI  - Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by
      Parkin.
AB  - Damage to mitochondria can lead to the depolarization of the inner mitochondrial
      membrane, thereby sensitizing impaired mitochondria for selective elimination by
      autophagy. However, fusion of uncoupled mitochondria with polarized mitochondria
      can compensate for damage, reverse membrane depolarization, and obviate
      mitophagy. Parkin, an E3 ubiquitin ligase that is mutated in monogenic forms of
      Parkinson's disease, was recently found to induce selective autophagy of damaged
      mitochondria. Here we show that ubiquitination of mitofusins Mfn1 and Mfn2, large
      GTPases that mediate mitochondrial fusion, is induced by Parkin upon membrane
      depolarization and leads to their degradation in a proteasome- and p97-dependent
      manner. p97, a AAA+ ATPase, accumulates on mitochondria upon uncoupling of Parkin
      expressing cells, and both p97 and proteasome activity are required for Parkin
      mediated mitophagy. After mitochondrial fission upon depolarization, Parkin
      prevents or delays refusion of mitochondria, likely by the elimination of
      mitofusins. Inhibition of Drp1-mediated mitochondrial fission, the proteasome, or
      p97 prevents Parkin-induced mitophagy.

PMID- 21173116
TI  - Chk1 inhibits replication factory activation but allows dormant origin firing in
      existing factories.
AB  - Replication origins are licensed by loading MCM2-7 hexamers before entry into S
      phase. However, only ~10% of licensed origins are normally used in S phase, with
      the others remaining dormant. When fork progression is inhibited, dormant origins
      initiate nearby to ensure that all of the DNA is eventually replicated. In
      apparent contrast, replicative stress activates ataxia telangiectasia and rad-3
      related (ATR) and Chk1 checkpoint kinases that inhibit origin firing. In this
      study, we show that at low levels of replication stress, ATR/Chk1 predominantly
      suppresses origin initiation by inhibiting the activation of new replication
      factories, thereby reducing the number of active factories. At the same time,
      inhibition of replication fork progression allows dormant origins to initiate
      within existing replication factories. The inhibition of new factory activation
      by ATR/Chk1 therefore redirects replication toward active factories where forks
      are inhibited and away from regions that have yet to start replication. This
      minimizes the deleterious consequences of fork stalling and prevents similar
      problems from arising in unreplicated regions of the genome.

PMID- 21173117
TI  - Natural killer-cell differentiation by myeloid progenitors.
AB  - Because lymphoid progenitors can give rise to natural killer (NK) cells, NK
      ontogeny has been considered to be exclusively lymphoid. Here, we show that rare
      human CD34(+) hematopoietic progenitors develop into NK cells in vitro in the
      presence of cytokines (interleukin-7, interleukin-15, stem cell factor, and fms
      like tyrosine kinase-3 ligand). Adding hydrocortisone and stromal cells greatly
      increases the frequency of progenitor cells that give rise to NK cells through
      the recruitment of myeloid precursors, including common myeloid progenitors and
      granulocytic-monocytic precursors to the NK-cell lineage. WNT signaling was
      involved in this effect. Cells at more advanced stages of myeloid differentiation
      (with increasing expression of CD13 and macrophage colony-stimulating factor
      receptor [M-CSFR]) could also differentiate into NK cells in the presence of
      cytokines, stroma, and hydrocortisone. NK cells derived from myeloid precursors
      (CD56(-)CD117(+)M-CSFR(+)) showed more expression of killer immunoglobulin-like
      receptors, a fraction of killer immunoglobulin-like receptor-positive-expressing
      cells that lacked NKG2A, a higher cytotoxicity compared with CD56(-)CD117(+)M
      CSFR(-) precursor-derived NK cells and thus resemble the CD56(dim) subset of NK
      cells. Collectively, these studies show that NK cells can be derived from the
      myeloid lineage.

PMID- 21173118
TI  - Selective induction of endothelial P2Y6 nucleotide receptor promotes vascular
      inflammation.
AB  - During a systemic inflammatory response endothelial-expressed surface molecules
      have been strongly implicated in orchestrating immune responses. Previous studies
      have shown enhanced extracellular nucleotide release during acute inflammatory
      conditions. Therefore, we hypothesized that endothelial nucleotide receptors
      could play a role in vascular inflammation. To address this hypothesis, we
      performed screening experiments and exposed human microvascular endothelia to
      inflammatory stimuli, followed by measurements of P2Y or P2X transcriptional
      responses. These studies showed a selective induction of the P2Y(6) receptor (> 4
      fold at 24 hours). Moreover, studies that used real-time reverse transcription
      polymerase chain reaction, Western blot analysis, or immunofluorescence confirmed
      time- and dose-dependent induction of P2Y(6) with tumor necrosis factor alpha or
      Lipopolysaccharide (LPS) stimulation in vitro and in vivo. Studies that used MRS
      2578 as P2Y(6) receptor antagonist showed attenuated nuclear factor kappaB
      reporter activity and proinflammatory gene expression in human microvascular
      endothelial cells in vitro. Moreover, pharmacologic or genetic in vivo studies
      showed attenuated inflammatory responses in P2Y(6)(-/-) mice or after P2Y(6)
      antagonist treatment during LPS-induced vascular inflammation. These studies show
      an important contribution of P2Y(6) signaling in enhancing vascular inflammation
      during systemic LPS challenge and implicate the P2Y(6) receptor as a therapeutic
      target during systemic inflammatory responses.

PMID- 21173119
TI  - The clinical pathologist as consultant.

PMID- 21173120
TI  - Pathology consultation on warfarin pharmacogenetic testing.

PMID- 21173121
TI  - Flow cytometric immunophenotyping of cerebrospinal fluid specimens.
AB  - Flow cytometric immunophenotyping (FCI) is recommended in the evaluation of
      cerebrospinal fluid (CSF) specimens for hematologic neoplasms. This study
      reviewed FCI of CSF specimens collected for primary diagnosis (n = 77) and follow
      up for known malignancy (n = 153). FCI was positive in 11 (4.8%) of 230
      specimens: acute myeloid leukemia, 6; precursor B-acute lymphoblastic leukemia,
      2; B-cell lymphoma, 2; and T-cell lymphoma, 1. Positive results were obtained in
      low-cellularity specimens, including 2 with fewer than 100 events in the
      population of interest. FCI was indeterminate in 19 (8.3%) of 230 specimens,
      including 3 with only sparse events, 8 with possible artifact (apparent lack of
      staining, nonspecific or background staining, and aspirated air), and 8 with
      phenotypic findings considered insufficient for diagnosis. Indeterminate
      specimens were often limited by low cellularity and lacked normal cell
      populations to evaluate for appropriate staining. FCI may be of value in low
      cellularity CSF specimens, although the results should be interpreted with
      caution.

PMID- 21173123
TI  - CD23 expression in follicular lymphoma: clinicopathologic correlations.
AB  - Follicular lymphoma (FL) is typically a CD10+/CD5-/FMC-7+ B-cell lymphoma with
      variable CD23 expression. The clinical significance of CD23 expression in FL is
      uncertain. We studied the expression of CD23 by flow cytometry in 69 lymph nodes
      (LNs) and correlated it with pathologic and clinical parameters. Of 69 FLs, 48
      (70%) were CD23+. Grade 3 FLs were CD23- more often (12/16 [75%]) than grade 1
      and 2 cases (9/53 [17%]; P < .001). CD23 expression was more common in FLs in
      inguinal LNs than in other sites: 20 of 23 (87%) vs 28 of 46 (61%; P = .029).
      Overall survival (P = .002) and event-free survival (P < .0001) were longer in
      the CD23+ group than in the CD23- FLs. Our study shows that grade 3 FLs are more
      often CD23- than lower grade FLs and that FLs in inguinal LNs are more frequently
      CD23+ than in LNs from other sites. Furthermore, our findings also indicate that
      survival is significantly better in CD23+ FLs.

PMID- 21173122
TI  - Acute myeloid leukemia with IDH1 or IDH2 mutation: frequency and
      clinicopathologic features.
AB  - Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are reported in
      acute myeloid leukemia (AML). We studied the frequency and the clinicopathologic
      features of IDH1 and IDH2 mutations in AML. Mutations in IDH1 (IDH1(R)132) and
      IDH2 (IDH2(R)172) were assessed by Sanger sequencing in 199 AML cases. Point
      mutations in IDH1(R)132 were detected in 12 (6.0%) of 199 cases and in IDH2(R)172
      in 4 (2.0%) of 196 cases. Of the 16 mutated cases, 15 (94%) were cytogenetically
      normal, for an overall frequency in this group of 11.8%. IDH1(R)132 and
      IDH2(R)172 mutations were mutually exclusive. Concurrent mutations in NPM1, FLT3,
      CEBPA, and NRAS were detected only in AML with the IDH1(R)132 mutation. The
      clinical and laboratory variables of patients with AML with IDH mutations showed
      no significant differences compared with patients with wild-type IDH. We conclude
      that IDH1(R)132 and IDH2(R)172 mutations occur most often in cytogenetically
      normal AML cases with an overall frequency of approximately 11.8%.

PMID- 21173124
TI  - The stromal cell marker SPARC predicts for survival in patients with diffuse
      large B-cell lymphoma treated with rituximab.
AB  - The cellular composition of the tumor microenvironment may affect survival in
      diffuse large B-cell lymphoma (DLBCL). We performed immunostains for 2 stromal
      cell markers, CD68 and SPARC (secreted protein, acidic and rich in cysteine), in
      262 patients with DLBCL treated with rituximab and cyclophosphamide, doxorubicin,
      vincristine, and prednisone (CHOP) or CHOP-like therapies. Patients with any
      SPARC+ cells in the microenvironment had a significantly longer overall survival,
      and patients with high SPARC positivity in the microenvironment also had a
      significantly longer event-free survival. Survival differences were mainly due to
      the prognostic effect of SPARC+ cells in activated B-cell (ABC)-type DLBCL, with
      no effect found in the germinal center B-cell-type DLBCL. Of clinical features
      examined, only the number of extranodal sites was significantly associated with
      SPARC expression. Multivariate analysis revealed that SPARC expression predicted
      patient survival independent of the International Prognostic Index or tumor cell
      of origin. SPARC expression in the microenvironment of DLBCL can be used for
      prognostic purposes, determining a subgroup of patients with ABC DLBCL who have
      significantly longer survival. More aggressive chemotherapy protocols should be
      considered for patients with ABC DLBCL without SPARC+ stromal cells. CD68
      expression by cells in the microenvironment did not predict survival.

PMID- 21173125
TI  - FLT3 and NPM1 mutations in myelodysplastic syndromes: Frequency and potential
      value for predicting progression to acute myeloid leukemia.
AB  - We reviewed FLT3 and NPM1 mutation data in a large cohort of patients with
      myelodysplastic syndrome (MDS). The frequencies of FLT3 and NPM1 mutation were
      2.0% and 4.4%, respectively, and mutations were restricted to cases of
      intermediate- and high-risk MDS. Cytogenetic abnormalities were identified in
      46.9% of cases. FLT3 mutations were associated with a complex karyotype (P =
      .009), whereas NPM1 mutations were associated with a diploid karyotype (P <
      .001). FLT3 mutation (P < .001) was associated with progression to acute myeloid
      leukemia (AML), as were a higher bone marrow (BM) blast count (P < .001) and
      complex cytogenetics (P = .039). No patient with an NPM1 mutation alone had
      disease that progressed to AML. Cox proportional regression multivariate analysis
      indicated that FLT3 mutation, NPM1 mutation, complex cytogenetics, BM blast
      count, pancytopenia, and age were independent factors that correlated with
      progression-free survival. We conclude that FLT3 and NPM1 mutations are rare in
      MDS, but assessment of mutation status is potentially useful for predicting
      progression to AML.

PMID- 21173126
TI  - Chlamydia psittaci Infection in nongastrointestinal extranodal MALT lymphomas and
      their precursor lesions.
AB  - Extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT)
      are associated with various infectious pathogens. We analyzed the presence of
      Chlamydia psittaci, Chlamydia pneumoniae, and Chlamydia trachomatis DNA in 47
      nongastrointestinal and 14 gastrointestinal MALT lymphomas, 37 nonmalignant
      control samples, and 27 autoimmune precursor lesions by polymerase chain reaction
      amplification and direct sequencing. In 47 nongastrointestinal MALT lymphomas, 13
      (28%) were positive for C psittaci DNA compared with 4 (11%) of 37 nonmalignant
      control samples (P = .09). C psittaci was detected at variable frequencies in
      MALT lymphomas of different sites: lung, 100% (5/5; P < .01); thyroid gland, 30%
      (3/10; P > .05); salivary gland, 13% (2/15; P > .05); ocular adnexa, 15% (2/13);
      and skin, 25% (1/4). Of 27 autoimmune precursor lesions (11 Hashimoto thyroiditis
      and 16 Sjogren syndrome), 11 (41%) contained C psittaci DNA. Only 1 (7%) of 14
      gastrointestinal MALT lymphomas was positive for C psittaci. All specimens were
      negative for C trachomatis and C pneumoniae. Besides ocular adnexal lymphomas, C
      psittaci infection is associated with nongastrointestinal MALT lymphomas and
      autoimmune precursor lesions, suggesting possible involvement of C psittaci
      induced antigenic-driven MALT lymphomagenesis.

PMID- 21173127
TI  - Flow cytometry rapidly identifies all acute promyelocytic leukemias with high
      specificity independent of underlying cytogenetic abnormalities.
AB  - Acute promyelocytic leukemia (APL) is a highly aggressive disease requiring
      prompt diagnosis and specific early intervention. Immunophenotyping by flow
      cytometry (FCM) facilitates a rapid diagnosis, but commonly used criteria are
      neither sufficiently sensitive nor specific. With an antibody panel for
      diagnostic screening in routine practice, we found all 149 APL cases in this
      study exhibited a unique immunophenotypic profile, ie, a characteristic CD11b-
      myeloid population and absent CD11c expression in all myeloid populations; 96.6%
      of cases also lacked HLA-DR expression. These distinctive features allowed
      recognition of all unusual cases phenotypically resembling the regular
      myeloblasts (CD34+/HLA-DR+) or granulocytes (CD117-/CD34-/HLA-DR-). FCM
      effectively identified all 19 APL cases with variant translocations, including
      cases with a normal karyotype due to a cryptic submicroscopic t(15;17)(q22;q21),
      t(11;17)(q23;q21) that escaped the detection by fluorescence in situ
      hybridization for t(15;17) and der(15)ider(17)(q10) that lacked a simple
      reciprocal t(15;17). When APL-associated profiles were validated against 107 AML
      cases of non-APL subtypes, including 51 HLA-DR- cases, the diagnostic specificity
      and positive predictive value were 98%. FCM effectively provides independent
      detection of APL during diagnostic workup and harmonizes with the subsequent
      molecular cytogenetic diagnosis.

PMID- 21173128
TI  - Thrombotic thrombocytopenic purpura and urinary tract infections: is there a
      connection?
AB  - Most cases of thrombotic thrombocytopenic purpura (TTP) are considered idiopathic
      without an identifiable etiologic agent. It has been previously reported that a
      number of patients with TTP had a urinary tract infection (UTI). Apheresis
      records were searched for patients with TTP from 1999 through 2007. Records were
      examined for evidence of UTI, and the patients were divided into 4 groups: 1,
      laboratory evidence of UTI on admission; 2, UTI just before admission; 3, UTI
      that developed during hospitalization; and 4, weak laboratory evidence of a UTI.
      The study included 90 TTP "visits." (A visit was defined as all admissions for
      TTP for a specific patient within a 1-month period.) Of the TTP visits, 21 (23%)
      were associated with UTIs. Group 1 included 7 patients; group 2, 10 patients;
      group 3, 3 patients; and group 4, 1 patient. This suggests that UTIs might serve
      as a TTP stimulus. Owing to the relatively strong association of UTIs with TTP,
      all patients with TTP should be screened for UTI and treated accordingly.

PMID- 21173129
TI  - Results of HLA antibody testing using ELISA vs the fluorescent bead method and
      retrospective review of data for recipients of packed RBCs and platelets from
      male HLA-immunized donors.
AB  - We reviewed HLA antibody testing results using an enzyme-linked immunosorbent
      assay (ELISA) for all male blood donors at our institution during a 3.5-month
      period to look for HLA immunization. Confirmatory testing of 33 blood samples
      positive for HLA class I and/or II antibodies was performed using the fluorescent
      bead method. A retrospective review of recipients of packed RBCs and platelets
      processed from these 33 HLA-immunized male donors were conducted to identify
      transfusion-related acute lung injury and cognate antigens. The agreement rates
      between the methods for HLA class I and II antibodies were 21% (7/33) and 6%
      (2/33), respectively. We noted HLA antibodies in the male donors corresponding to
      cognate antigens in 2 recipients of packed RBCs and in 3 recipients of platelets.
      Of 8 donors positive for HLA antibodies, 5 did not have a history of blood
      transfusion. We conclude that ELISA was too sensitive and had a high false
      positive rate for the detection of HLA class II antibodies.

PMID- 21173130
TI  - ABO blood type and longevity.
AB  - To assess the observation that blood type B might be a marker for longevity, we
      reviewed the records and determined the ABO blood types of all patients who died
      in our hospital in 2004. Age was stratified by decade of death, and linear
      regressions were calculated by ABO percentage. ABO survival curves were compared.
      In 2004, 906 patients died; 35 were excluded (stillborn infants). Of the
      remaining 871 patients, ABO types were available for 772 (88.6%). The percentage
      of patients with group B blood declined with age (P < .01). None of the other
      blood type percentages had a statistically significant increase or decrease. The
      group B survival curve was statistically worse than non-B groups (P <= .01);
      there were no differences in survival among groups A, O, and AB (P =.47). In our
      patient population, the percentage of patients with group B blood declines with
      age. The survival curve in group B was worse than that in groups A, O, and AB.
      These findings suggest that in our patient population, blood group B is not a
      marker for longevity but may be a marker for earlier death.

PMID- 21173131
TI  - Multivariate analysis of clinical, demographic, and laboratory data for
      classification of disorders of calcium homeostasis.
AB  - Parathyroid hormone (PTH) nomograms combine total calcium and intact PTH (iPTH)
      measurements to classify disorders of calcium homeostasis. Our objective was to
      determine if using a combination of laboratory, demographic, and clinical
      parameters improves the accuracy of classification of these disorders. Chart data
      were collected for 236 patients with physician-ordered iPTH and total calcium
      tests. Classification was done using 3 approaches: (1) PTH nomogram plotting
      total calcium and iPTH results against known cases; (2) review of all available
      chart data ("gold standard"); and (3) multivariate model (classification and
      regression tree [CART] or logistic regression) using 24 variables. The CART model
      was developed using the gold standard patient classification and validated using
      leave-one-out cross-validation. The CART model was significantly (P = .002) more
      accurate (80.6%) than the PTH nomogram (59.7%) and logistic regression (66.2%) at
      classifying calcium homeostasis disorders. The CART model used 6 of 24 variables
      (iPTH, calcium, creatinine, renal transplantation, percentage of females, and
      urea nitrogen) and had a misclassification error rate of 0.194 (27/139).
      Classification of disorders of calcium homeostasis based on the PTH nomogram can
      be improved by using the CART model developed in this study.

PMID- 21173132
TI  - Utilization management in a large urban academic medical center: a 10-year
      experience.
AB  - Management of laboratory test utilization presents an ongoing challenge. Most
      studies reported in the literature have described efforts to control one or a few
      tests, but the results cannot be generalized to a broader utilization management
      strategy. Herein we report our experiences with an organizational utilization
      management program during a 10-year period. Cumulatively, our program has
      achieved significant success, saving millions of dollars in blood components and
      reducing inpatient tests per discharge by 26%. Highlights from our experiences
      include the importance of implementing an institutional organizational structure
      to support utilization management, the central role fulfilled by clinical
      pathologists as leaders of the program, the ability to obtain timely utilization
      data, and careful selection of the most appropriate implementation tools tailored
      to the unique circumstances of each utilization management initiative.

PMID- 21173133
TI  - Identification of microRNAs From the miR-371~373 and miR-302 clusters as
      potential serum biomarkers of malignant germ cell tumors.
AB  - Current serum biomarkers for diagnosis and monitoring of malignant germ cell
      tumors (GCTs) show limited sensitivity and specificity. We previously observed
      that microRNAs of the miR-371~373 and miR-302 clusters are overexpressed in all
      malignant GCTs, regardless of patient age, histologic subtype, or anatomic site,
      but are not reported to be coordinately up-regulated in other tumor types or
      disease states. Herein we show that levels of all 8 main members of the miR
      371~373 and miR-302 clusters were elevated in the serum of a 4-year-old boy at
      the time of diagnosis of yolk sac tumor. Levels returned to normal during an
      uneventful clinical follow-up, with kinetics similar to those of the conventional
      marker alpha-fetoprotein. We describe in detail the multiplex polymerase chain
      reaction protocol used to quantify serum microRNA levels, which is highly robust
      and reproducible. Our study indicates that miR-371~373 and miR-302 cluster
      microRNAs are promising candidate biomarkers for improving disease monitoring
      (and potentially diagnosis) in malignant GCTs.

PMID- 21173134
TI  - Pure sarcomatoid carcinoma of maxillary sinus and nasal cavity simulating
      malignant fibrous histiocytoma.
AB  - Although a few cases of sinonasal carcinoma with focal sarcomatous
      differentiation have been reported, pure sarcomatoid carcinoma has not been
      reported in the English literature. Imaging studies and gross inspection in a 60
      year-old man with left-sided face pain revealed a mass in the left maxillary
      sinus and nasal cavity. A large incisional biopsy specimen from the nasal cavity
      revealed proliferation of malignant spindle and round cells with a malignant
      fibrous histiocytoma (MFH) pattern. Tumor giant cells were scattered, and there
      were areas of a vague storiform pattern. Mitotic figures were numerous.
      Carcinomatous component was not recognized. The histologic diagnosis was
      storiform-pleomorphic MFH. Tumor cells were positive for pancytokeratins AE1/3,
      KL-1, and CAM5.2 and cytokeratin (CK) 18, vimentin, CD68, p53, Ki-67 (labeling,
      90%), alpha1-antitrypsin, and alpha1-antichymotrypsin and negative for
      pancytokeratin WSS, CK 34betaE14, CK7, CK8, CK14, CK19, CK20, epithelial membrane
      antigen, S-100 protein, desmin, alpha-smooth muscle actin, CD34, HMB45,
      chromogranin, synaptophysin, myoglobin, CD45, CD30, and CD15. Because keratins
      were positive in tumor cells, a diagnosis of sarcomatoid carcinoma simulating MFH
      was made. The patient was treated with chemoradiation without significant effect
      and died 9 months after initial examination.

PMID- 21173135
TI  - The changing spectrum of DNA-based specimen provenance testing in surgical
      pathology.
AB  - Short tandem repeat (STR) analysis has emerged as the method of choice for
      testing to resolve specimen source contamination and identity problems that arise
      in surgical pathology. We studied a series of consecutive cases referred for STR
      typing during a 5-year period to document the usefulness of the approach and to
      describe the broadening scope of testing. The series demonstrates that STR-based
      typing can be applied in virtually any setting in which specimen source
      confirmation is requested, that STR-based typing is informative in 92% of cases,
      but that exceptions occasionally arise that complicate test interpretation. The
      series also demonstrates that in addition to traditional uses of STR typing,
      testing is now performed in the absence of any direct indication that a specimen
      mix-up or contamination may have occurred, namely, when the pathologic findings
      are unexpected or the clinical setting is atypical. The case series underscores
      the ability of STR testing to detect errors that cannot be captured by current
      laboratory protocols, a finding that has important implications for patient
      safety.

PMID- 21173136
TI  - The predictive value of the fine-needle aspiration diagnosis "suspicious for a
      follicular neoplasm, hurthle cell type" in patients with hashimoto thyroiditis.
AB  - A fine-needle aspiration sample composed exclusively of Hurthle cells is
      interpreted as "suspicious for a follicular neoplasm, Hurthle cell type"
      (SFNHCT). Because some nonneoplastic Hurthle cell proliferations in Hashimoto
      thyroiditis (HT) mimic this cytologic pattern, we examined the positive
      predictive value (PPV) for malignancy of SFNHCT in patients with HT. Between 1992
      and 2007, 401 patients with cytologic findings of SFNHCT were identified at 3
      institutions. Histologic follow-up was available for 287 (71.6%), and malignancy
      was diagnosed in 69 (24.0%). Malignancy was present in 2 (PPV = 9.5%) of 21
      patients with HT compared with 67 (PPV = 25.2%) of 266 patients without HT (P =
      .081). Although the difference in the rate of malignancy between the HT and non
      HT cohorts did not reach statistical significance, the lower risk of malignancy
      in the HT cohort more closely approximates the risk of cases interpreted as
      "atypia of undetermined significance." For this reason, it might be appropriate
      for Hurthle cell-only aspirates from patients with HT to be categorized as either
      atypia of undetermined significance or SFNHCT.

PMID- 21173137
TI  - Cytopathologic detection of circulating tumor cells using the isolation by size
      of epithelial tumor cell method: promises and pitfalls.
AB  - Detection of circulating tumor cells (CTCs) morphologically may be a promising
      new approach in clinical oncology. We tested the reliability of a cytomorphologic
      approach to identify CTCs: 808 blood samples from patients with benign and
      malignant diseases and healthy volunteers were examined using the isolation by
      size of epithelial tumor cell (ISET) method. Cells having nonhematologic features
      (so-called circulating nonhematologic cells [CNHCs]) were classified into 3
      categories: CNHCs with malignant features, CNHCs with uncertain malignant
      features, and CNHCs with benign features. CNHCs were found in 11.1% and 48.9% of
      patients with nonmalignant and malignant pathologies, respectively (P < .001).
      CNHCs with malignant features were observed in 5.3% and in 43.1% of patients with
      nonmalignant and malignant pathologies, respectively. Cytopathologic
      identification of CTCs using the ISET method represents a promising field for
      cytopathologists. The possibility of false-positive diagnosis stresses the need
      for using ancillary methods to improve this approach.

PMID- 21173138
TI  - A UK NEQAS ISH multicenter ring study using the Ventana HER2 dual-color ISH
      assay.
AB  - We performed a multicenter assessment of a new HER2 dual-color chromogenic in
      situ hybridization (CISH) test and herein report on concordance of CISH data with
      fluorescence in situ hybridization (FISH) data and intraobserver and
      interlaboratory scoring consistency. HER2 results were evaluated using duplicate
      cores from 30 breast cancers in 5 laboratories using the Ventana HER2 dual-color
      ISH assay (Ventana Medical Systems, Cambridgeshire, England) and in 1 central
      laboratory using a standard FISH assay. Overall 93.3% of cases were successfully
      analyzed by CISH across the 5 participating laboratories. There was excellent
      concordance (98.0% overall) for diagnosis of HER2 amplification by CISH compared
      with FISH. Intraobserver variability (7.7%) and intersite variability (9.1%) of
      absolute HER2/chromosome enumeration probe 17 ratios were tightly controlled
      across all participating laboratories. The Ventana HER2 dual-color ISH assay is
      robust and reproducible, shows good concordance with a standard FISH assay, and
      complies with requirements in national and international guidelines for
      performance of ISH-based diagnostic tests.

PMID- 21173139
TI  - Indirect methods for TSH reference interval: at last fit for purpose?

PMID- 21173140
TI  - Health disorders and ergonomic concerns from the use of the microscope: a voice
      from the past.

PMID- 21173141
TI  - Fixation time does not affect the expression of estrogen receptor.

PMID- 21173142
TI  - Is the aberrant expression of p53 by immunocytochemistry a surrogate marker of
      TP53 mutation and/or deletion in chronic lymphocytic leukemia?

PMID- 21173143
TI  - Dopamine D1-histamine H3 receptor heteromers provide a selective link to MAPK
      signaling in GABAergic neurons of the direct striatal pathway.
AB  - Previously, using artificial cell systems, we identified receptor heteromers
      between the dopamine D(1) or D(2) receptors and the histamine H(3) receptor. In
      addition, we demonstrated two biochemical characteristics of the dopamine D(1)
      receptor-histamine H(3) receptor heteromer. We have now extended this work to
      show the dopamine D(1) receptor-histamine H(3) receptor heteromer exists in the
      brain and serves to provide a novel link between the MAPK pathway and the
      GABAergic neurons in the direct striatal efferent pathway. Using the biochemical
      characteristics identified previously, we found that the ability of H(3) receptor
      activation to stimulate p44 and p42 extracellular signal-regulated MAPK (ERK 1/2)
      phosphorylation was only observed in striatal slices of mice expressing D(1)
      receptors but not in D(1) receptor-deficient mice. On the other hand, the ability
      of both D(1) and H(3) receptor antagonists to block MAPK activation induced by
      either D(1) or H(3) receptor agonists was also found in striatal slices. Taken
      together, these data indicate the occurrence of D(1)-H(3) receptor complexes in
      the striatum and, more importantly, that H(3) receptor agonist-induced ERK 1/2
      phosphorylation in striatal slices is mediated by D(1)-H(3) receptor heteromers.
      Moreover, H(3) receptor-mediated phospho-ERK 1/2 labeling co-distributed with
      D(1) receptor-containing but not with D(2) receptor-containing striatal neurons.
      These results indicate that D(1)-H(3) receptor heteromers work as processors
      integrating dopamine- and histamine-related signals involved in controlling the
      function of striatal neurons of the direct striatal pathway.

PMID- 21173144
TI  - Membrane topology of NAADP-sensitive two-pore channels and their regulation by N
      linked glycosylation.
AB  - Two-pore channels (TPCs) localize to the endolysosomal system and have recently
      emerged as targets for the Ca(2+)-mobilizing messenger, nicotinic acid adenine
      dinucleotide phosphate (NAADP). However, their membrane topology is unknown.
      Using fluorescence protease protection assays, we show that human TPC1 and TPC2
      possess cytosolic N and C termini and therefore an even number of transmembrane
      regions. Fluorophores placed at position 225 or 347 in TPC1, or 339 in TPC2 were
      also cytosolic, whereas a fluorophore at position 628 in TPC1 was luminal. These
      data together with sequence similarity to voltage-gated Ca(2+) and Na(+)
      channels, and unbiased in silico predictions are consistent with a topology in
      which two homologous domains are present, each comprising 6 transmembrane regions
      and a re-entrant pore loop. Immunocytochemical analysis of selectively
      permeabilized cells using antipeptide antibodies confirmed that the C-terminal
      tails of recombinant TPCs are cytosolic and that residues 240-254 of TPC2 prior
      to putative pore 1 are luminal. Both TPC1 and TPC2 are N-glycosylated with
      residues 599, 611, and 616 contributing to glycosylation of TPC1. This confirms
      the luminal position of these residues, which immediately precede the putative
      pore loop of the second domain. Mutation of all three glycosylation sites in TPC1
      enhances NAADP-evoked cytosolic Ca(2+) signals. Our data establish essential
      features of the topology of two-pore channels.

PMID- 21173145
TI  - ATP induces conformational changes in the carboxyl-terminal region of ClC-5.
AB  - ATP binding enhances the activity of ClC-5, the transporter mutated in Dent
      disease, a disease affecting the renal proximal tubule. Previously, the ATP
      binding site was revealed in x-ray crystal structures of the cytoplasmic region
      of this membrane protein. Disruption of this site by mutagenesis (Y617A-ClC-5)
      reduced the functional expression and ATP-dependent regulation of the full-length
      transporter in Xenopus oocytes. However, insight into the conformational changes
      underlying ATP-dependent regulation is lacking. Here, we show that ATP binding
      induces a change in protein conformation. Specifically, small angle x-ray
      scattering experiments indicate that ATP binding promotes a clamp-like closure of
      the isolated ClC-5 carboxyl-terminal region. Limited proteolysis studies show
      that ATP binding induces conformational compaction of the carboxyl-terminal
      region in the intact membrane protein as well. In the context of fibroblasts and
      proximal tubule epithelial cells, disruption of the ATP binding site in full
      length ClC-5 (Y617A-ClC-5) led to a defect in processing and trafficking out of
      the endoplasmic reticulum. These latter findings account for the decrease in
      functional expression previously reported for this ATP-binding mutant and prompt
      future study of a model whereby conformational compaction caused by ATP binding
      promotes biosynthetic maturation.

PMID- 21173146
TI  - ATP modulates interaction of syntaxin-1A with sulfonylurea receptor 1 to regulate
      pancreatic beta-cell KATP channels.
AB  - ATP-sensitive potassium (K(ATP)) channels are regulated by a variety of cytosolic
      factors (adenine nucleotides, Mg(2+), phospholipids, and pH). We previously
      reported that K(ATP) channels are also regulated by endogenous membrane-bound
      SNARE protein syntaxin-1A (Syn-1A), which binds both nucleotide-binding folds of
      sulfonylurea receptor (SUR)1 and 2A, causing inhibition of K(ATP) channel
      activity in pancreatic islet beta-cells and cardiac myocytes, respectively. In
      this study, we show that ATP dose-dependently inhibits Syn-1A binding to SUR1 at
      physiological concentrations, with the addition of Mg(2+) causing a decrease in
      the ATP-induced inhibitory effect. This ATP disruption of Syn-1A binding to SUR1
      was confirmed by FRET analysis in living HEK293 cells. Electrophysiological
      studies in pancreatic beta-cells demonstrated that reduced ATP concentrations
      increased K(ATP) channel sensitivity to Syn-1A inhibition. Depletion of
      endogenous Syn-1A in insulinoma cells by botulinum neurotoxin C1 proteolysis
      followed by rescue with exogenous Syn-1A showed that Syn-1A modulates K(ATP)
      channel sensitivity to ATP. Thus, our data indicate that although both ATP and
      Syn-1A independently inhibit beta-cell K(ATP) channel gating, they could also
      influence the sensitivity of K(ATP) channels to each other. These findings
      provide new insight into an alternate mechanism by which ATP regulates pancreatic
      beta-cell K(ATP) channel activity, not only by its direct actions on Kir6.2 pore
      subunit, but also via ATP modulation of Syn-1A binding to SUR1.

PMID- 21173147
TI  - Complex contribution of cyclophilin D to Ca2+-induced permeability transition in
      brain mitochondria, with relation to the bioenergetic state.
AB  - Cyclophilin D (cypD)-deficient mice exhibit resistance to focal cerebral ischemia
      and to necrotic but not apoptotic stimuli. To address this disparity, we
      investigated isolated brain and in situ neuronal and astrocytic mitochondria from
      cypD-deficient and wild-type mice. Isolated mitochondria were challenged by high
      Ca(2+), and the effects of substrates and respiratory chain inhibitors were
      evaluated on permeability transition pore opening by light scatter. In situ
      neuronal and astrocytic mitochondria were visualized by mito-DsRed2 targeting and
      challenged by calcimycin, and the effects of glucose, NaCN, and an uncoupler were
      evaluated by measuring mitochondrial volume. In isolated mitochondria, Ca(2+)
      caused a large cypD-dependent change in light scatter in the absence of
      substrates that was insensitive to Ruthenium red or Ru360. Uniporter inhibitors
      only partially affected the entry of free Ca(2+) in the matrix. Inhibition of
      complex III/IV negated the effect of substrates, but inhibition of complex I was
      protective. Mitochondria within neurons and astrocytes exhibited cypD-independent
      swelling that was dramatically hastened when NaCN and 2-deoxyglucose were present
      in a glucose-free medium during calcimycin treatment. In the presence of an
      uncoupler, cypD-deficient astrocytic mitochondria performed better than wild-type
      mitochondria, whereas the opposite was observed in neurons. Neuronal mitochondria
      were examined further during glutamate-induced delayed Ca(2+) deregulation. CypD
      knock-out mitochondria exhibited an absence or a delay in the onset of
      mitochondrial swelling after glutamate application. Apparently, some conditions
      involving deenergization render cypD an important modulator of PTP in the brain.
      These findings could explain why absence of cypD protects against necrotic
      (deenergized mitochondria), but not apoptotic (energized mitochondria) stimuli.

PMID- 21173148
TI  - Only two residues are responsible for the dramatic difference in receptor binding
      between swine and new pandemic H1 hemagglutinin.
AB  - In view of its critical role in influenza A virus (IAV) tropism and pathogenesis,
      we evaluated the receptor binding properties of HA proteins of the closely
      related swine and new pandemic human IAVs. We generated recombinant soluble
      trimeric H1 ectodomains of several IAVs and analyzed their sialic acid binding
      properties using fetuin-binding and glycan array analysis. The results show that
      closely related swine and new pandemic H1 proteins differ dramatically in their
      ability to bind these receptors. Although new pandemic H1 protein exhibited
      hardly any binding, swine H1 bound efficiently to a number of alpha2-6-linked
      sialyl glycans. The responsible amino acids were identified by analyzing chimeric
      H1 proteins and by performing systematic site-directed mutagenesis of swine and
      new pandemic human H1 proteins. The difference was found to map to residues at
      positions 200 and 227. Although substitution of either residue significantly
      affected the binding phenotype, substitution of both was found to act
      synergistically and reverse the phenotype almost completely. Modeling of the
      T200A and E227A substitutions into the crystal structure of the new pandemic
      human H1 protein revealed the loss of potential hydrogen bond formation with
      Gln(191), which is part of the 190-loop of the receptor binding site, and with
      the penultimate galactose, respectively. Thus, a residue not belonging to the
      receptor binding site may affect the interaction of HA with its receptor.
      Interestingly, whereas alanine at position 200 is found in most new pandemic
      human viruses, the residue at position 227 in these viruses is invariably a
      glutamic acid.

PMID- 21173149
TI  - Post-translational modifications of the gamma-subunit affect intracellular
      trafficking and complex assembly of GlcNAc-1-phosphotransferase.
AB  - GlcNAc-1-phosphotransferase plays a key role in the generation of mannose 6
      phosphate, a recognition marker essential for efficient transport of lysosomal
      hydrolases to lysosomes. The enzyme complex is composed of six subunits
      (alpha(2)beta(2)gamma(2)). The alpha- and beta-subunits are catalytically active,
      whereas the function of the gamma-subunit is still unclear. We have investigated
      structural properties, localization, and intracellular transport of the human and
      mouse gamma-subunits and the molecular requirements for the assembly of the
      phosphotransferase complex. The results showed that endogenous and overexpressed
      gamma-subunits were localized in the cis-Golgi apparatus. Secreted forms of gamma
      subunits were detectable in media of cultured cells as well as in human serum.
      The gamma-subunit contains two in vivo used N-glycosylation sites at positions 88
      and 115, equipped with high mannose-type oligosaccharides. (35)S pulse-chase
      experiments and size exclusion chromatography revealed that the majority of non
      glycosylated gamma-subunit mutants were integrated in high molecular mass
      complexes, failed to exit the endoplasmic reticulum (ER), and were rapidly
      degraded. The substitution of cysteine 245 involved in dimerization of gamma
      subunits impaired neither ER exit nor trafficking through the secretory pathway.
      Monomeric gamma-subunits failed, however, to associate with other GlcNAc-1
      phosphotransferase subunits. The data provide evidence that assembly of the
      GlcNAc-1-phosphotransferase complex takes place in the ER and requires
      dimerization of the gamma-subunits.

PMID- 21173150
TI  - Yeast cells lacking all known ceramide synthases continue to make complex
      sphingolipids and to incorporate ceramides into glycosylphosphatidylinositol
      (GPI) anchors.
AB  - In yeast, the inositolphosphorylceramides mostly contain C26:0 fatty acids.
      Inositolphosphorylceramides were considered to be important for viability because
      the inositolphosphorylceramide synthase AUR1 is essential. However, lcb1Delta
      cells, unable to make sphingoid bases and inositolphosphorylceramides, are viable
      if they harbor SLC1-1, a gain of function mutation in the 1-acyl-glycerol-3
      phosphate acyltransferase SLC1. SLC1-1 allows the incorporation of C26:0 fatty
      acids into phosphatidylinositol (PI), thus generating PI", an abnormal, C26
      containing PI, presumably acting as surrogate for inositolphosphorylceramide.
      Here we show that the lethality of the simultaneous deletion of the known
      ceramide synthases LAG1/LAC1/LIP1 and YPC1/YDC1 can be rescued by the expression
      of SLC1-1 or the overexpression of AUR1. Moreover, lag1Delta lac1Delta ypc1Delta
      ydc1Delta (4Delta) quadruple mutants have been reported to be viable in certain
      genetic backgrounds but to still make some abnormal uncharacterized inositol
      containing sphingolipids. Indeed, we find that 4Delta quadruple mutants make
      substantial amounts of unphysiological inositolphosphorylphytosphingosines but
      that they also still make small amounts of normal inositolphosphorylceramides.
      Moreover, 4Delta strains incorporate exogenously added sphingoid bases into
      inositolphosphorylceramides, indicating that these cells still possess an unknown
      pathway allowing the synthesis of ceramides. 4Delta cells also still add quite
      normal amounts of ceramides to glycosylphosphatidylinositol anchors. Synthesis of
      inositolphosphorylceramides and inositolphosphorylphytosphingosines is operated
      by Aur1p and is essential for growth of all 4Delta cells unless they contain SLC1
      1. PI", however, is made without the help of Aur1p. Furthermore, mannosylation of
      PI" is required for the survival of sphingolipid-deficient strains, which depend
      on SLC1-1. In contrast to lcb1Delta SLC1-1, 4Delta SLC1-1 cells grow at 37 
      degrees C but remain thermosensitive at 44  degrees C.

PMID- 21173151
TI  - Sphingosine-1-phosphate lyase deficiency produces a pro-inflammatory response
      while impairing neutrophil trafficking.
AB  - Sphingosine-1-phosphate (S1P) lyase catalyzes the degradation of S1P, a potent
      signaling lysosphingolipid. Mice with an inactive S1P lyase gene are impaired in
      the capacity to degrade S1P, resulting in highly elevated S1P levels. These S1P
      lyase-deficient mice have low numbers of lymphocytes and high numbers of
      neutrophils in their blood. We found that the S1P lyase-deficient mice exhibited
      features of an inflammatory response including elevated levels of pro
      inflammatory cytokines and an increased expression of genes in liver associated
      with an acute-phase response. However, the recruitment of their neutrophils into
      inflamed tissues was impaired and their neutrophils were defective in migration
      to chemotactic stimulus. The IL-23/IL-17/granulocyte-colony stimulating factor (G
      CSF) cytokine-controlled loop regulating neutrophil homeostasis, which is
      dependent on neutrophil trafficking to tissues, was disturbed in S1P lyase
      deficient mice. Deletion of the S1P4 receptor partially decreased the
      neutrophilia and inflammation in S1P lyase-deficient mice, implicating S1P
      receptor signaling in the phenotype. Thus, a genetic block in S1P degradation
      elicits a pro-inflammatory response but impairs neutrophil migration from blood
      into tissues.

PMID- 21173152
TI  - A Na+-translocating pyrophosphatase in the acetogenic bacterium Acetobacterium
      woodii.
AB  - The anaerobic acetogenic bacterium Acetobacterium woodii employs a novel type of
      Na(+)-motive anaerobic respiration, caffeate respiration. However, this
      respiration is at the thermodynamic limit of energy conservation, and even worse,
      in the first step, caffeate is activated by caffeyl-CoA synthetase, which
      hydrolyzes ATP to AMP and pyrophosphate. Here, we have addressed whether or not
      the energy stored in the anhydride bond of pyrophosphate is conserved by A.
      woodii. Inverted membrane vesicles of A. woodii have a membrane-bound
      pyrophosphatase that catalyzes pyrophosphate hydrolysis at a rate of 70-120
      milliunits/mg of protein. Pyrophosphatase activity was dependent on the divalent
      cation Mg(2+). In addition, activity was strictly dependent on Na(+) with a K(m)
      of 1.1 mM. Hydrolysis of pyrophosphate was accompanied by (22)Na(+) transport
      into the lumen of the inverted membrane vesicles. Inhibitor studies revealed that
      (22)Na(+) transport was primary and electrogenic. Next to the Na(+)-motive
      ferredoxin:NAD(+) oxidoreductase (Fno or Rnf), the Na(+)-pyrophosphatase is the
      second primary Na(+)-translocating enzyme in A. woodii.

PMID- 21173153
TI  - EGR1 and EGR2 involvement in vertebrate tendon differentiation.
AB  - The molecules involved in vertebrate tendon formation during development remain
      largely unknown. To date, only two DNA-binding proteins have been identified as
      being involved in vertebrate tendon formation, the basic helix-loop-helix
      transcription factor Scleraxis and, recently, the Mohawk homeobox gene. We
      investigated the involvement of the early growth response transcription factors
      Egr1 and Egr2 in vertebrate tendon formation. We established that Egr1 and Egr2
      expression in tendon cells was correlated with the increase of collagen
      expression during tendon cell differentiation in embryonic limbs. Vertebrate
      tendon differentiation relies on a muscle-derived FGF (fibroblast growth factor)
      signal. FGF4 was able to activate the expression of Egr genes and that of the
      tendon-associated collagens in chick limbs. Egr gene misexpression experiments
      using the chick model allowed us to establish that either Egr gene has the
      ability to induce de novo expression of the reference tendon marker scleraxis,
      the main tendon collagen Col1a1, and other tendon-associated collagens Col3a1,
      Col5a1, Col12a1, and Col14a1. Mouse mutants for Egr1 or Egr2 displayed reduced
      amounts of Col1a1 transcripts and a decrease in the number of collagen fibrils in
      embryonic tendons. Moreover, EGR1 and EGR2 trans-activated the mouse Col1a1
      proximal promoter and were recruited to the tendon regulatory regions of this
      promoter. These results identify EGRs as novel DNA-binding proteins involved in
      vertebrate tendon differentiation by regulating type I collagen production.

PMID- 21173154
TI  - Activated protein C enhances human keratinocyte barrier integrity via sequential
      activation of epidermal growth factor receptor and Tie2.
AB  - Keratinocytes play a critical role in maintaining epidermal barrier function.
      Activated protein C (APC), a natural anticoagulant with anti-inflammatory and
      endothelial barrier protective properties, significantly increased the barrier
      impedance of keratinocyte monolayers, measured by electric cell substrate
      impedance sensing and FITC-dextran flux. In response to APC, Tie2, a tyrosine
      kinase receptor, was rapidly activated within 30 min, and relocated to cell-cell
      contacts. APC also increased junction proteins zona occludens, claudin-1 and VE
      cadherin. Inhibition of Tie2 by its peptide inhibitor or small interfering RNA
      abolished the barrier protective effect of APC. Interestingly, APC did not
      activate Tie2 through its major ligand, angiopoietin-1, but instead acted by
      binding to endothelial protein C receptor, cleaving protease-activated receptor-1
      and transactivating EGF receptor. Furthermore, when activation of Akt, but not
      ERK, was inhibited, the barrier protective effect of APC on keratinocytes was
      abolished. Thus, APC activates Tie2, via a mechanism requiring, in sequential
      order, the receptors, endothelial protein C receptor, protease-activated receptor
      1, and EGF receptor, which selectively enhances the PI3K/Akt signaling to enhance
      junctional complexes and reduce keratinocyte permeability.

PMID- 21173155
TI  - Zymophagy, a novel selective autophagy pathway mediated by VMP1-USP9x-p62,
      prevents pancreatic cell death.
AB  - Autophagy has recently elicited significant attention as a mechanism that either
      protects or promotes cell death, although different autophagy pathways, and the
      cellular context in which they occur, remain to be elucidated. We report a
      thorough cellular and biochemical characterization of a novel selective autophagy
      that works as a protective cell response. This new selective autophagy is
      activated in pancreatic acinar cells during pancreatitis-induced vesicular
      transport alteration to sequester and degrade potentially deleterious activated
      zymogen granules. We have coined the term "zymophagy" to refer to this process.
      The autophagy-related protein VMP1, the ubiquitin-protease USP9x, and the
      ubiquitin-binding protein p62 mediate zymophagy. Moreover, VMP1 interacts with
      USP9x, indicating that there is a close cooperation between the autophagy pathway
      and the ubiquitin recognition machinery required for selective autophagosome
      formation. Zymophagy is activated by experimental pancreatitis in genetically
      engineered mice and cultured pancreatic acinar cells and by acute pancreatitis in
      humans. Furthermore, zymophagy has pathophysiological relevance by controlling
      pancreatitis-induced intracellular zymogen activation and helping to prevent cell
      death. Together, these data reveal a novel selective form of autophagy mediated
      by the VMP1-USP9x-p62 pathway, as a cellular protective response.

PMID- 21173158
TI  - Contact sexual offending by men with online sexual offenses.
AB  - There is much concern about the likelihood that online sexual offenders
      (particularly online child pornography offenders) have either committed or will
      commit offline sexual offenses involving contact with a victim. This study
      addresses this question in two meta-analyses: the first examined the contact
      sexual offense histories of online offenders, whereas the second examined the
      recidivism rates from follow-up studies of online offenders. The first meta
      analysis found that approximately 1 in 8 online offenders (12%) have an
      officially known contact sexual offense history at the time of their index
      offense (k = 21, N = 4,464). Approximately one in two (55%) online offenders
      admitted to a contact sexual offense in the six studies that had self-report data
      (N = 523). The second meta-analysis revealed that 4.6% of online offenders
      committed a new sexual offense of some kind during a 1.5- to 6-year follow-up (k
      = 9, N = 2,630); 2.0% committed a contact sexual offense and 3.4% committed a new
      child pornography offense. The results of these two quantitative reviews suggest
      that there may be a distinct subgroup of online-only offenders who pose
      relatively low risk of committing contact sexual offenses in the future.

PMID- 21173156
TI  - Emerging role of alpha2,6-sialic acid as a negative regulator of galectin binding
      and function.
AB  - Galectins are beta-galactoside-binding lectins that regulate diverse cell
      behaviors, including adhesion, migration, proliferation, and apoptosis. Galectins
      can be expressed both intracellularly and extracellularly, and extracellular
      galectins mediate their effects by associating with cell-surface
      oligosaccharides. Despite intensive current interest in galectins, strikingly few
      studies have focused on a key enzyme that acts to inhibit galectin signaling,
      namely beta-galactoside alpha2,6-sialyltransferase (ST6Gal-I). ST6Gal-I adds an
      alpha2,6-linked sialic acid to the terminal galactose of N-linked glycans, and
      this modification blocks galectin binding to beta-galactosides. This minireview
      summarizes the evidence suggesting that ST6Gal-I activity serves as an "off
      switch" for galectin function.

PMID- 21173159
TI  - beta-Arrestin 1 inhibits the GTPase-activating protein function of ARHGAP21,
      promoting activation of RhoA following angiotensin II type 1A receptor
      stimulation.
AB  - Activation of the small GTPase RhoA following angiotensin II stimulation is known
      to result in actin reorganization and stress fiber formation. Full activation of
      RhoA, by angiotensin II, depends on the scaffolding protein beta-arrestin 1,
      although the mechanism behind its involvement remains elusive. Here we uncover a
      novel partner and function for beta-arrestin 1, namely, in binding to ARHGAP21
      (also known as ARHGAP10), a known effector of RhoA activity, whose GTPase
      activating protein (GAP) function it inhibits. Using yeast two-hybrid screening,
      a peptide array, in vitro binding studies, truncation analyses, and
      coimmunoprecipitation techniques, we show that beta-arrestin 1 binds directly to
      ARHGAP21 in a region that transects the RhoA effector GAP domain. Moreover, we
      show that the level of a complex containing beta-arrestin 1 and ARHGAP21 is
      dynamically increased following angiotensin stimulation and that the kinetics of
      this interaction modulates the temporal activation of RhoA. Using information
      gleaned from a peptide array, we developed a cell-permeant peptide that serves to
      inhibit the interaction of these proteins. Using this peptide, we demonstrate
      that disruption of the beta-arrestin 1/ARHGAP21 complex results in a more active
      ARHGAP21, leading to less-efficient signaling via the angiotensin II type 1A
      receptor and, thereby, attenuation of stimulated stress fiber formation.

PMID- 21173160
TI  - TDP-43 is directed to stress granules by sorbitol, a novel physiological osmotic
      and oxidative stressor.
AB  - TDP-43, or TAR DNA-binding protein 43, is a pathological marker of a spectrum of
      neurodegenerative disorders, including amyotrophic lateral sclerosis and
      frontotemporal lobar degeneration with ubiquitin-positive inclusions. TDP-43 is
      an RNA/DNA-binding protein implicated in transcriptional and posttranscriptional
      regulation. Recent work also suggests that TDP-43 associates with cytoplasmic
      stress granules, which are transient structures that form in response to stress.
      In this study, we establish sorbitol as a novel physiological stressor that
      directs TDP-43 to stress granules in Hek293T cells and primary cultured glia. We
      quantify the association of TDP-43 with stress granules over time and show that
      stress granule association and size are dependent on the glycine-rich region of
      TDP-43, which harbors the majority of pathogenic mutations. Moreover, we
      establish that cells harboring wild-type and mutant TDP-43 have distinct stress
      responses: mutant TDP-43 forms significantly larger stress granules, and is
      incorporated into stress granules earlier, than wild-type TDP-43; in striking
      contrast, wild-type TDP-43 forms more stress granules over time, but the granule
      size remains relatively unchanged. We propose that mutant TDP-43 alters stress
      granule dynamics, which may contribute to the progression of TDP-43
      proteinopathies.

PMID- 21173161
TI  - Cse4 (CenH3) association with the Saccharomyces cerevisiae plasmid partitioning
      locus in its native and chromosomally integrated states: implications in
      centromere evolution.
AB  - The histone H3 variant Cse4 specifies centromere identity in Saccharomyces
      cerevisiae by its incorporation into a special nucleosome positioned at CEN DNA
      and promotes the assembly of the kinetochore complex, which is required for
      faithful chromosome segregation. Our previous work showed that Cse4 is also
      associated with the partitioning locus STB of the 2MUm circle--a multicopy
      plasmid that resides in the yeast nucleus and propagates itself stably. Cse4 is
      essential for the functional assembly of the plasmid partitioning complex,
      including the recruitment of the yeast cohesin complex at STB. We have located
      Cse4 association strictly at the origin-proximal subregion of STB. Three of the
      five directly repeated tandem copies of a 62-bp consensus sequence element
      constituting this region are necessary and sufficient for the recruitment of
      Cse4. The association of Cse4 with STB is dependent on Scm3, the loading factor
      responsible for the incorporation of Cse4 into the CEN nucleosome. A
      chromosomally integrated copy of STB confers on the integration site the capacity
      for Cse4 association as well as cohesin assembly. The localization of Cse4 in
      chromatin digested by micrococcal nuclease is consistent with the potential
      assembly of one Cse4-containing nucleosome, but not more than two, at STB. The
      remarkable ability of STB to acquire a very specialized, and strictly regulated,
      chromosome segregation factor suggests its plausible evolutionary kinship with
      CEN.

PMID- 21173163
TI  - The kinetoplast duplication cycle in Trypanosoma brucei is orchestrated by
      cytoskeleton-mediated cell morphogenesis.
AB  - The mitochondrial DNA of Trypanosoma brucei is organized in a complex structure
      called the kinetoplast. In this study, we define the complete kinetoplast
      duplication cycle in T. brucei based on three-dimensional reconstructions from
      serial-section electron micrographs. This structural model was enhanced by
      analyses of the replication process of DNA maxi- and minicircles. Novel insights
      were obtained about the earliest and latest stages of kinetoplast duplication. We
      show that kinetoplast S phase occurs concurrently with the repositioning of the
      new basal body from the anterior to the posterior side of the old flagellum. This
      emphasizes the role of basal body segregation in kinetoplast division and
      suggests a possible mechanism for driving the rotational movement of the
      kinetoplast during minicircle replication. Fluorescence in situ hybridization
      with minicircle- and maxicircle-specific probes showed that maxicircle DNA is
      stretched out between segregated minicircle networks, indicating that maxicircle
      segregation is a late event in the kinetoplast duplication cycle. This new view
      of the complexities of kinetoplast duplication emphasizes the dependencies
      between the dynamic remodelling of the cytoskeleton and the inheritance of the
      mitochondrial genome.

PMID- 21173162
TI  - Genetic requirements and meiotic function of phosphorylation of the yeast axial
      element protein Red1.
AB  - The synaptonemal complex (SC) is a meiosis-specific tripartite structure that
      forms between two homologous chromosomes; it consists of a central region and two
      parallel lateral elements. Lateral elements also are called axial elements prior
      to synapsis. In Saccharomyces cerevisiae, Red1, Hop1, and Mek1 are structural
      components of axial/lateral elements. The red1/mek1/hop1 mutants all exhibit
      reduced levels of interhomolog recombination and produce no viable spores. Red1
      is a phosphoprotein. Several earlier reports proposed that phosphorylated Red1
      plays important roles in meiosis, including in signaling meiotic DNA damage or in
      preventing exit from the pachytene chromosomes. We report here that the
      phosphorylation of Red1 is carried out in CDC28-dependent and CDC28-independent
      manners. In contrast to previous results, we found Red1 phosphorylation to be
      independent of meiotic DNA recombination, the Mec1/Tel1 DNA damage checkpoint
      kinases, and the Mek1 kinase. To functionally validate the phosphorylation of
      Red1, we mapped the phosphorylation sites on this protein. A red1(14A) mutant
      showing no detectable Red1 phosphorylation did not exhibit decreased sporulation
      efficiency, defects in viable spore production, or defects in meiotic DNA damage
      checkpoints. Thus, our results suggest that the phosphorylation of Red1 is not
      essential for its functions in meiosis.

PMID- 21173164
TI  - Ligand-stimulated downregulation of the alpha interferon receptor: role of
      protein kinase D2.
AB  - Alpha interferon (IFN-alpha) controls homeostasis of hematopoietic stem cells,
      regulates antiviral resistance, inhibits angiogenesis, and suppresses tumor
      growth. This cytokine is often used to treat cancers and chronic viral
      infections. The extent of cellular responses to IFN-alpha is limited by the IFN
      induced ubiquitination and degradation of the IFN-alpha/beta receptor chain 1
      (IFNAR1) chain of the cognate receptor. IFNAR1 ubiquitination is facilitated by
      the betaTrcp E3 ubiquitin ligase that is recruited to IFNAR1 upon its degron
      phosphorylation, which is induced by the ligand. Here we report identification of
      protein kinase D2 (PKD2) as a kinase that mediates the ligand-inducible
      phosphorylation of IFNAR1 degron and enables binding of betaTrcp to the receptor.
      Treatment of cells with IFN-alpha induces catalytic activity of PKD2 and
      stimulates its interaction with IFNAR1. Expression and kinase activity of PKD2
      are required for the ligand-inducible stimulation of IFNAR1 ubiquitination and
      endocytosis and for accelerated proteolytic turnover of IFNAR1. Furthermore,
      inhibition or knockdown of PKD2 robustly augments intracellular signaling induced
      by IFN-alpha and increases the efficacy of its antiviral effects. The mechanisms
      of the ligand-inducible elimination of IFNAR1 are discussed, along with the
      potential medical significance of this regulation.

PMID- 21173165
TI  - Human globin knock-in mice complete fetal-to-adult hemoglobin switching in
      postnatal development.
AB  - Elevated levels of fetal gamma-globin can cure disorders caused by mutations in
      the adult beta-globin gene. This clinical finding has motivated studies to
      improve our understanding of hemoglobin switching. Unlike humans, mice do not
      express a distinct fetal globin. Transgenic mice that contain the human beta
      globin locus complete their fetal-to-adult hemoglobin switch prior to birth, with
      human gamma-globin predominantly restricted to primitive erythroid cells. We
      established humanized (100% human hemoglobin) knock-in mice that demonstrate a
      distinct fetal hemoglobin (HbF) stage, where gamma-globin is the dominant globin
      chain produced during mid- to late gestation. Human gamma- and beta-globin gene
      competition is evident around the time of birth, and gamma-globin chain
      production diminishes in postnatal life, with transient production of HbF
      reticulocytes. Following completion of the gamma- to-beta-globin switch, adult
      erythroid cells synthesize low levels of HbF. We conclude that the knock-in
      globin genes are expressed in a pattern strikingly similar to that in human
      development, most notably with postnatal resolution of the fetal-to-adult
      hemoglobin switch. Our findings are consistent with the importance of BCL11A in
      hemoglobin switching, since removal of intergenic binding sites for BCL11A
      results in human gamma-globin expression in mouse definitive erythroid cells.

PMID- 21173166
TI  - Genomic profiling of HMGN1 reveals an association with chromatin at regulatory
      regions.
AB  - The interaction of architectural proteins such as the linker histone H1 and high
      mobility-group (HMG) proteins with nucleosomes leads to changes in chromatin
      structure and histone modifications and alters the cellular transcription
      profile. The interaction of HMG proteins with chromatin is dynamic. However, it
      is not clear whether the proteins are constantly and randomly redistributed among
      all the nucleosomes or whether they preferentially associate with, and turn over
      at, specific regions in chromatin. To address this question, we examined the
      genome-wide distribution of the nucleosome binding protein HMGN1 and compared it
      to that of regulatory chromatin marks. We find that HMGN1 is not randomly
      distributed throughout the genome. Instead, the protein preferentially localizes
      to DNase I hypersensitive (HS) sites, promoters, functional enhancers, and
      transcription factor binding sites. Our results suggest that HMGN1 is part of the
      cellular machinery that modulates transcriptional fidelity by generating,
      maintaining, or preferentially interacting with specific sites in chromatin.

PMID- 21173167
TI  - Evolutionarily conserved, growth plate zone-specific regulation of the matrilin-1
      promoter: L-Sox5/Sox6 and Nfi factors bound near TATA finely tune activation by
      Sox9.
AB  - To help uncover the mechanisms underlying the staggered expression of cartilage
      specific genes in the growth plate, we dissected the transcriptional mechanisms
      driving expression of the matrilin-1 gene (Matn1). We show that a unique assembly
      of evolutionarily conserved cis-acting elements in the Matn1 proximal promoter
      restricts expression to the proliferative and prehypertrophic zones of the growth
      plate. These elements functionally interact with distal elements and likewise are
      capable of restricting the domain of activity of a pancartilaginous Col2a1
      enhancer. The proximal elements include a Pe1 element binding the chondrogenic L
      Sox5, Sox6, and Sox9 proteins, a SI element binding Nfi proteins, and an
      initiator Ine element binding the Sox trio and other factors. Sox9 binding to Pe1
      is indispensable for functional interaction with the distal promoter. Binding of
      L-Sox5/Sox6 to Ine and Nfib to SI modulates Sox9 transactivation in a protein
      dose-dependent manner, possibly to enhance Sox9 activity in early stages of
      chondrogenesis and repress it at later stages. Hence, our data suggest a novel
      model whereby Sox and Nfi proteins bind to conserved Matn1 proximal elements and
      functionally interact with each other to finely tune gene expression in specific
      zones of the cartilage growth plate.

PMID- 21173169
TI  - A prospective cohort study on overweight, smoking, alcohol consumption, and risk
      of Barrett's esophagus.
AB  - BACKGROUND: Barrett's esophagus (BE) is a precursor lesion of esophageal
      adenocarcinoma. Besides gastroesophageal reflux, possible risk factors for BE
      include overweight, cigarette smoking, and alcohol consumption. Our objective was
      to study these associations by using prospective data. METHODS: The prospective
      Netherlands Cohort Study, initiated in 1986, consists of 120,852 men and women,
      aged 55 to 69 years at baseline. At baseline, all subjects completed a
      questionnaire on dietary habits and lifestyle. After 16.3 years of follow-up, 370
      BE cases with specialized intestinal metaplasia and 3,866 subcohort members were
      available for case-cohort analysis. Cox proportional hazards models were used to
      calculate incidence rate ratios (RR) and 95% CIs. RESULTS: Body mass index (BMI)
      at baseline was associated with risk of BE in women [multivariable adjusted RR
      per 1 kg/m(2), 1.07 (1.03-1.11)] but not in men [RR per 1 kg/m(2), 0.99 (0.93
      1.05)]. The association in women was not specifically due to abdominal
      overweight. Former cigarette smokers were at increased risk of BE (RR = 1.33, 95%
      CI: 1.00-1.77), but current smokers were not. Smoking duration showed a positive
      association with BE risk (P(trend) = 0.03). For alcohol consumption, the RR per
      10 g ethanol/d was 0.95 (0.87-1.03). CONCLUSIONS: Increased BMI was a risk factor
      for BE in women but not in men. Several aspects of cigarette smoking were
      positively associated with BE risk. Alcohol consumption was not associated with
      an increased risk of BE. IMPACT: Future research should focus on risk factors
      both for development and for progression of BE to esophageal adenocarcinoma.

PMID- 21173168
TI  - Bax activation by engagement with, then release from, the BH3 binding site of Bcl
      xL.
AB  - Bcl-2 homologues (such as Bcl-x(L)) promote survival in part through
      sequestration of "activator" BH3-only proteins (such as Puma), preventing them
      from directly activating Bax. It is thus assumed that inhibition of interactions
      between activators and Bcl-x(L) is a prerequisite for small molecules to
      antagonize Bcl-x(L) and induce cell death. The biological properties, described
      here of a terphenyl-based alpha-helical peptidomimetic inhibitor of Bcl-x(L)
      attest that displacement of Bax from Bcl-x(L) is also critical. Terphenyl 14
      triggers Bax-dependent but Puma-independent cell death, disrupting Bax/Bcl-x(L)
      interactions without affecting Puma/Bcl-x(L) interactions. In cell-free assays,
      binding of inactive Bax to Bcl-x(L), followed by its displacement from Bcl-x(L)
      by terphenyl 14, produces mitochondrially permeabilizing Bax molecules. Moreover,
      the peptidomimetic kills yeast cells that express Bax and Bcl-x(L), and it uses
      Bax-binding Bcl-x(L) to induce mammalian cell death. Likewise, ectopic expression
      of Bax in yeast and mammalian cells enhances sensitivity to another Bcl-x(L)
      inhibitor, ABT-737, when Bcl-x(L) is present. Thus, the interaction of Bcl-x(L)
      with Bax paradoxically primes Bax at the same time it keeps Bax activity in
      check, and displacement of Bax from Bcl-x(L) triggers an apoptotic signal by
      itself. This mechanism might contribute to the clinical efficiency of Bcl-x(L)
      inhibitors.

PMID- 21173170
TI  - Early natural history of incident, type-specific human papillomavirus infections
      in newly sexually active young women.
AB  - BACKGROUND: Characterizing short-term detection patterns of young women's
      incident alpha-genus human papillomavirus (HPV) infections may further our
      understanding of HPV transmission. METHODS: Between 2000 and 2007, we followed 18
      to 22-year-old female university students with triannual HPV DNA and
      Papanicolaou testing. Using Kaplan-Meier methods, we estimated duration of
      detectable, type-specific incident infections; time to redetection (among
      infections that became undetectable); and time to cervical lesion development
      after incident infection. We evaluated risk factors for short-term persistent
      versus transient infection with logistic regression. RESULTS: Three hundred three
      incident, type-specific infections were detected in 85 sexually active women.
      Median time to first negative test after incident infection was 9.4 (95% CI: 7.8
      11.2) months; 90.6% of infections became undetectable within 2 years. About 19.4%
      of infections that became undetectable were redetected within 1 year. Cervical
      lesions were common and 60% were positive for multiple HPV types in concurrent
      cervical swabs. Incident HPV detection in the cervix only (vs. the vulva/vagina
      only or both sites) was associated with short-term transience. CONCLUSIONS:
      Although most incident infections became undetectable within 2 years, redetection
      was common. Cervical lesions were a common early manifestation of HPV infection.
      IMPACT: It remains unclear whether potentially modifiable risk factors can be
      identified to reduce infection duration (and transmission likelihood).

PMID- 21173171
TI  - Serum C-reactive protein and risk of pancreatic cancer in two nested, case
      control studies.
AB  - BACKGROUND: Many epidemiologic studies have examined the association between C
      reactive protein (CRP) and risk of cancer with inconsistent results. METHODS: We
      conducted two nested, case-control studies in the Alpha-Tocopherol, Beta-Carotene
      Cancer Prevention Study (ATBC) and Prostate, Lung, Colorectal, and Ovarian Cancer
      Screening Trial (PLCO) to test whether prediagnostic circulating CRP
      concentrations were associated with pancreatic adenocarcinoma. Between 1985 and
      2004, 311 cases occurred in ATBC and between 1994 and 2006, 182 cases occurred in
      PLCO. Controls (n = 510 in ATBC, n = 374 in PLCO) were alive at the time the case
      was diagnosed and were matched by age, date of blood draw, sex, and race. We used
      conditional logistic regression adjusted for smoking to calculate OR and 95% CI
      for pancreatic cancer. RESULTS: CRP concentrations (ng/mL) tended to be inversely
      or not associated with pancreatic cancer risk in ATBC, PLCO, and combined
      analyses [per standardized quintile increase in CRP, continuous OR = 0.94 (95%
      CI, 0.89-0.99), OR = 0.99 (95% CI, 0.95-1.04), OR = 0.98 (95% CI, 0.95-1.01),
      respectively]. In combined analyses, we observed a significant interaction
      (P(interaction) = 0.02) such that inverse associations were suggestive in younger
      (OR = 0.95; 95% CI, 0.90-1.01), but not older, participants. CONCLUSION: Our
      results do not support the hypothesis that higher CRP concentrations are
      associated with incident pancreatic cancer. IMPACT: Our results highlight the
      importance of investigating more specific biomarkers for inflammation that may
      reflect the biological mechanisms underlying pancreatic cancer in prospective
      cohort studies.

PMID- 21173172
TI  - Increased mortality with accessory gene regulator (agr) dysfunction in
      Staphylococcus aureus among bacteremic patients.
AB  - Accessory gene regulator (agr) dysfunction in Staphylococcus aureus has been
      associated with a longer duration of bacteremia. We aimed to assess the
      independent association between agr dysfunction in S. aureus bacteremia and 30
      day in-hospital mortality. This retrospective cohort study included all adult
      inpatients with S. aureus bacteremia admitted between 1 January 2003 and 30 June
      2007. Severity of illness prior to culture collection was measured using the
      modified acute physiology score (APS). agr dysfunction in S. aureus was
      identified semiquantitatively by using a delta-hemolysin production assay. Cox
      proportional hazard models were used to measure the association between agr
      dysfunction and 30-day in-hospital mortality, statistically adjusting for patient
      and pathogen characteristics. Among 814 patient admissions complicated by S.
      aureus bacteremia, 181 (22%) patients were infected with S. aureus isolates with
      agr dysfunction. Overall, 18% of patients with agr dysfunction in S. aureus died,
      compared to 12% of those with functional agr in S. aureus (P = 0.03). There was a
      trend toward higher mortality among patients with S. aureus with agr dysfunction
      (adjusted hazard ratio [HR], 1.34; 95% confidence interval [CI], 0.87 to 2.06).
      Among patients with the highest APS (scores of >28), agr dysfunction in S. aureus
      was significantly associated with mortality (adjusted HR, 1.82; 95% CI, 1.03 to
      3.21). This is the first study to demonstrate an independent association between
      agr dysfunction and mortality among severely ill patients. The delta-hemolysin
      assay examining agr function may be a simple and inexpensive approach to
      predicting patient outcomes and potentially optimizing antibiotic therapy.

PMID- 21173173
TI  - Comparative efficacy and safety of moxifloxacin and clindamycin in the treatment
      of odontogenic abscesses and inflammatory infiltrates: a phase II, double-blind,
      randomized trial.
AB  - Moxifloxacin penetrates well into oromaxillary tissue and covers the causative
      pathogens that show an increasing resistance to standard antibiotics. Clinical
      reports suggest that moxifloxacin may be effective for the treatment of
      odontogenic infections that can lead to serious complications. The objective of
      this prospective, randomized, double-blind, multicenter study was to compare the
      efficacies and safeties of moxifloxacin and clindamycin for the medical treatment
      of patients with gingival inflammatory infiltrates and as an adjuvant therapy for
      patients with odontogenic abscesses requiring surgical treatment. Patients
      received either 400 mg moxifloxacin per os once daily or 300 mg clindamycin per
      os four times daily for 5 days consecutively. The primary efficacy endpoint was
      the percent reduction in patients' perceived pain on a visual analogue scale at
      days 2 to 3 from baseline. Primary analysis included 21 moxifloxacin- and 19
      clindamycin-treated patients with infiltrates and 15 moxifloxacin- and 16
      clindamycin-treated patients with abscesses. The mean pain reductions were 61.0%
      (standard deviation [SD], 46.9%) with moxifloxacin versus 23.4% (SD, 32.1%) with
      clindamycin (P = 0.006) for patients with infiltrates and 55.8% (SD, 24.8%) with
      moxifloxacin versus 42.7% (SD, 48.5%) with clindamycin (P = 0.358) for patients
      with abscesses. A global efficacy assessment at days 2 to 3 and 5 to 7 showed
      faster clinical responses with moxifloxacin in both abscess and infiltrate
      patients. Rates of adverse events were lower in moxifloxacin- than in clindamycin
      treated patients. In patients with inflammatory infiltrates, moxifloxacin was
      significantly more effective in reducing pain at days 2 to 3 of therapy than
      clindamycin. No significant differences between groups were found for patients
      with odontogenic abscesses.

PMID- 21173174
TI  - In vitro effect of qnrA1, qnrB1, and qnrS1 genes on fluoroquinolone activity
      against isogenic Escherichia coli isolates with mutations in gyrA and parC.
AB  - This article provides an analysis of the in vitro effect of qnrA1, qnrB1, and
      qnrS1 genes, combined with quinolone-resistant Ser83Leu substitutions in GyrA
      and/or Ser80Arg in ParC, on fluoroquinolone (FQ) resistance in isogenic
      Escherichia coli strains. The association of Ser83Leu substitution in GyrA,
      Ser80Arg substitution in ParC, and qnr gene expression increased the MIC of
      ciprofloxacin to 2 MUg/ml. qnr genes present in E. coli that harbored a Ser83Leu
      substitution in GyrA increased mutant prevention concentration (MPC) values to 8
      to 32 MUg/ml. qnr gene expression in E. coli may play an important role in
      selecting for one-step FQ-resistant mutants.

PMID- 21173175
TI  - Site-specific mutation of Staphylococcus aureus VraS reveals a crucial role for
      the VraR-VraS sensor in the emergence of glycopeptide resistance.
AB  - An initial response of Staphylococcus aureus to encounter with cell wall-active
      antibiotics occurs by transmembrane signaling systems that orchestrate changes in
      gene expression to promote survival. Histidine kinase two-component sensor
      response regulators such as VraRS contribute to this response. In this study, we
      examined VraS membrane sensor phosphotransfer signal transduction and explored
      the genetic consequences of disrupting signaling by engineering a site-specific
      vraS chromosomal mutation. We have used in vitro autophosphorylation assay with
      purified VraS[64-347] lacking its transmembrane anchor region and tested site
      specific kinase domain histidine mutants. We identified VraS H156 as the probable
      site of autophosphorylation and show phosphotransfer in vitro using purified
      VraR. Genetic studies show that the vraS(H156A) mutation in three strain
      backgrounds (ISP794, Newman, and COL) fails to generate detectable first-step
      reduced susceptibility teicoplanin mutants and severely reduces first-step
      vancomycin mutants. The emergence of low-level glycopeptide resistance in strain
      ISP794, derived from strain 8325 (DeltarsbU), did not require a functional
      sigma(B), but rsbU restoration could enhance the emergence frequency supporting a
      role for this alternative sigma factor in promoting glycopeptide resistance.
      Transcriptional analysis of vraS(H156A) strains revealed a pronounced reduction
      but not complete abrogation of the vraRS operon after exposure to cell wall
      active antibiotics, suggesting that additional factors independent of VraS-driven
      phosphotransfer, or sigma(B), exist for this promoter. Collectively, our results
      reveal important details of the VraRS signaling system and predict that
      pharmacologic blockade of the VraS sensor kinase will have profound effects on
      blocking emergence of cell wall-active antibiotic resistance in S. aureus.

PMID- 21173176
TI  - Inhibitory effects of 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranose on biofilm
      formation by Staphylococcus aureus.
AB  - 1,2,3,4,6-Penta-O-galloyl-beta-D-glucopyranose (PGG) is an active ingredient in
      plants that are commonly used in Chinese medicine to treat inflammation. We
      demonstrate here that PGG, at 6.25 MUM, does not inhibit the growth of
      Staphylococcus aureus, and yet it prevents biofilm formation on polystyrene and
      polycarbonate surfaces. At the same concentration, PGG is not toxic to human
      epithelial and fibroblast cells. PGG has an IB50 value, i.e., the PGG
      concentration that inhibits 50% biofilm formation, of 3.6 MUM. The value is
      substantially lower than that of N-acetylcysteine, iodoacetamide, and N-phenyl
      maleimide, which are known to inhibit biofilm formation by S. aureus. Biochemical
      and scanning electron microscopy results also reveal that PGG inhibits initial
      attachment of the bacteria to solid surface and the synthesis of polysaccharide
      intercellular adhesin, explaining how PGG inhibits biofilm formation. The results
      of this study demonstrate that coating PGG on polystyrene and silicon rubber
      surfaces with polyaniline prevents biofilm formation, indicating that PGG is
      highly promising for clinical use in preventing biofilm formation by S. aureus.

PMID- 21173178
TI  - Porphyromonas gingivalis cysteine proteinase inhibition by kappa-casein peptides.
AB  - Porphyromonas gingivalis is a major pathogen associated with chronic
      periodontitis, an inflammatory disease of the supporting tissues of the teeth.
      The Arg-specific (RgpA/B) and Lys-specific (Kgp) cysteine proteinases of P.
      gingivalis are major virulence factors for the bacterium. In this study kappa
      casein(109-137) was identified in a chymosin digest of casein as an inhibiting
      peptide of the P. gingivalis proteinases. The peptide was synthesized and shown
      to inhibit proteolytic activity associated with P. gingivalis whole cells,
      purified RgpA-Kgp proteinase-adhesin complexes, and purified RgpB proteinase. The
      peptide kappa-casein(109-137) exhibited synergism with Zn(II) against both Arg-
      and Lys-specific proteinases. The active region for inhibition was identified as
      kappa-casein(117-137) using synthetic peptides. Kinetic studies revealed that
      kappa-casein(109-137) inhibits in an uncompetitive manner. A molecular model
      based on the uncompetitive action and its synergistic ability with Zn(II) was
      developed to explain the mechanism of inhibition. Preincubation of P. gingivalis
      with kappa-casein(109-137) significantly reduced lesion development in a murine
      model of infection.

PMID- 21173179
TI  - Complete nucleotide sequence of plasmid pTN48, encoding the CTX-M-14 extended
      spectrum beta-lactamase from an Escherichia coli O102-ST405 strain.
AB  - The sequence of pTN48, a plasmid of the FII-FIB replicon type that encodes a CTX
      M-14 enzyme in an Escherichia coli strain of the phylogenetic group D2 O102-ST405
      clone, was determined. pTN48 is, for the most part, a mosaic of virulence,
      antibiotic resistance, and addiction system modules found in various other
      plasmids. The presence of multiple addiction systems indicates that the plasmid
      should be stably maintained in the E. coli clone, favoring dissemination of the
      CTX-M-14 enzyme.

PMID- 21173177
TI  - Inhibitors of endoplasmic reticulum alpha-glucosidases potently suppress
      hepatitis C virus virion assembly and release.
AB  - alpha-Glucosidases I and II are endoplasmic reticulum-resident enzymes that are
      essential for N-linked glycan processing and subsequent proper folding of
      glycoproteins. In this report, we first demonstrate that downregulation of the
      expression of alpha-glucosidase I, II, or both in Huh7.5 cells by small hairpin
      RNA technology inhibited the production of hepatitis C virus (HCV). In agreement
      with the essential role of alpha-glucosidases in HCV envelope glycoprotein
      processing and folding, treatment of HCV-infected cells with a panel of imino
      sugar derivatives, which are competitive inhibitors of alpha-glucosidases, did
      not affect intracellular HCV RNA replication and nonstructural protein expression
      but resulted in the inhibition of glycan processing and subsequent degradation of
      HCV E2 glycoprotein. As a consequence, HCV virion assembly and secretion were
      inhibited. In searching for imino sugars with better antiviral activity, we found
      that a novel imino sugar, PBDNJ0804, had a superior ability to inhibit HCV virion
      assembly and secretion. In summary, we demonstrated that glucosidases are
      important host factor-based antiviral targets for HCV infection. The low
      likelihood of drug-resistant virus emergence and potent antiviral efficacy of the
      novel glucosidase inhibitor hold promise for its development as a therapeutic
      agent for the treatment of chronic hepatitis C.

PMID- 21173180
TI  - Miconazole oral gel increases exposure to oral oxycodone by inhibition of CYP2D6
      and CYP3A4.
AB  - Our aim was to assess the effect of miconazole oral gel on the pharmacokinetics
      of oral oxycodone. In an open crossover study with two phases, 12 healthy
      volunteers took a single oral dose of 10 mg of immediate-release oxycodone with
      or without thrice-daily 85-mg miconazole oral gel treatment. The plasma
      concentrations of oxycodone and its oxidative metabolites were measured for 48 h.
      Pharmacological effects of oxycodone were recorded for 12 h. Pharmacokinetic
      parameters were compared by use of the geometric mean ratios (GMRs) and their 90%
      confidence interval (CIs). Pretreatment with miconazole oral gel caused a strong
      inhibition of the CYP2D6-dependent metabolism and moderate inhibition of the
      CYP3A4-dependent metabolism of oxycodone. The mean area under the concentration
      time curve (AUC) from time zero to infinity (AUC(0-infinity); GMR, 1.63; 90% CI,
      1.48 to 1.79) and the peak concentration of oxycodone (GMR, 1.31; 90% CI, 1.19 to
      1.44) were increased. The AUC of the CYP2D6-dependent metabolite oxymorphone was
      greatly decreased (GMR, 0.17; 90% CI, 0.09 to 0.31) by miconazole gel, whereas
      that of the CYP3A4-dependent metabolite noroxycodone was increased (GMR, 1.30;
      90% CI, 1.15 to 1.47) by miconazole gel. Differences in the pharmacological
      response to oxycodone between phases were insignificant. Miconazole oral gel
      increases the exposure to oral oxycodone, but the clinical relevance of the
      interaction is moderate. Miconazole oral gel produces a rather strong inhibitory
      effect on CYP2D6, which deserves further study.

PMID- 21173181
TI  - Nonoptimal DNA topoisomerases allow maintenance of supercoiling levels and
      improve fitness of Streptococcus pneumoniae.
AB  - Fluoroquinolones, which target gyrase and topoisomerase IV, are used for treating
      Streptococcus pneumoniae infections. Fluoroquinolone resistance in this bacterium
      can arise via point mutation or interspecific recombination with genetically
      related streptococci. Our previous study on the fitness cost of resistance
      mutations and recombinant topoisomerases identified GyrAE85K as a high-cost
      change. However, this cost was compensated for by the presence of a recombinant
      topoisomerase IV (parC and parE recombinant genes) in strain T14. In this study,
      we purified wild-type and mutant topoisomerases and compared their enzymatic
      activities. In strain T14, both gyrase carrying GyrAE85K and recombinant
      topoisomerase IV showed lower activities (from 2.0- to 3.7-fold) than the wild
      type enzymes. These variations of in vitro activity corresponded to changes of in
      vivo supercoiling levels that were analyzed by two-dimensional electrophoresis of
      an internal plasmid. Strains carrying GyrAE85K and nonrecombinant topoisomerases
      had lower (11.1% to 14.3%) supercoiling density (sigma) values than the wild
      type. Those carrying GyrAE85K and recombinant topoisomerases showed either
      partial or total supercoiling level restoration, with sigma values being 7.9%
      (recombinant ParC) and 1.6% (recombinant ParC and recombinant ParE) lower than
      those for the wild type. These data suggested that changes acquired by
      interspecific recombination might be selected because they reduce the fitness
      cost associated with fluoroquinolone resistance mutations. An increase in the
      incidence of fluoroquinolone resistance, even in the absence of further
      antibiotic exposure, is envisaged.

PMID- 21173182
TI  - Concentrations of tenofovir and emtricitabine in breast milk of HIV-1-infected
      women in Abidjan, Cote d'Ivoire, in the ANRS 12109 TEmAA Study, Step 2.
AB  - The aim was to evaluate emtricitabine (FTC) and tenofovir (TFV) neonatal
      ingestion through breast milk. Median TFV and FTC breast milk doses represented
      0.03% and 2%, respectively, of the proposed oral infant doses. Neonatal simulated
      plasma concentrations were extremely low for TFV but between the half-maximal
      inhibitory concentration and the adult minimal expected concentration for FTC.
      The rare children who will acquire HIV despite TDF-FTC therapy will need to be
      monitored for viral resistance acquisition.

PMID- 21173183
TI  - Efflux-mediated antibiotic resistance in Acinetobacter spp.
AB  - Among Acinetobacter spp., A. baumannii is the most frequently implicated in
      nosocomial infections, in particular in intensive care units. It was initially
      thought that multidrug resistance (MDR) in this species was due mainly to
      horizontal acquisition of resistance genes. However, it has recently become
      obvious that increased expression of chromosomal genes for efflux systems plays a
      major role in MDR. Among the five superfamilies of pumps, resistance-nodulation
      division (RND) systems are the most prevalent in multiply resistant A. baumannii.
      RND pumps typically exhibit a wide substrate range that can include antibiotics,
      dyes, biocides, detergents, and antiseptics. Overexpression of AdeABC, secondary
      to mutations in the adeRS genes encoding a two-component regulatory system,
      constitutes a major mechanism of multiresistance in A. baumannii. AdeIJK,
      intrinsic to this species, is responsible for natural resistance, but since
      overexpression above a certain threshold is toxic for the host, its contribution
      to acquired resistance is minimal. The recently described AdeFGH, probably
      regulated by a LysR-type transcriptional regulator, also confers multidrug
      resistance when overexpressed. Non-RND efflux systems, such as CraA, AmvA, AbeM,
      and AbeS, have also been characterized for A. baumannii, as have AdeXYZ and AdeDE
      for other Acinetobacter spp. Finally, acquired narrow-spectrum efflux pumps, such
      as the major facilitator superfamily (MFS) members TetA, TetB, CmlA, and FloR and
      the small multidrug resistance (SMR) member QacE in Acinetobacter spp., have been
      detected and are mainly encoded by mobile genetic elements.

PMID- 21173184
TI  - Characterization of the biosynthesis gene cluster for the pyrrole polyether
      antibiotic calcimycin (A23187) in Streptomyces chartreusis NRRL 3882.
AB  - The pyrrole polyether antibiotic calcimycin (A23187) is a rare ionophore that is
      specific for divalent cations. It is widely used as a biochemical and
      pharmacological tool because of its multiple, unique biological effects. Here we
      report on the cloning, sequencing, and mutational analysis of the 64-kb
      biosynthetic gene cluster from Streptomyces chartreusis NRRL 3882. Gene
      replacements confirmed the identity of the gene cluster, and in silico analysis
      of the DNA sequence revealed 27 potential genes, including 3 genes for the
      biosynthesis of the alpha-ketopyrrole moiety, 5 genes that encode modular type I
      polyketide synthases for the biosynthesis of the spiroketal ring, 4 genes for the
      biosynthesis of 3-hydroxyanthranilic acid, an N-methyltransferase tailoring gene,
      a resistance gene, a type II thioesterase gene, 3 regulatory genes, 4 genes with
      other functions, and 5 genes of unknown function. We propose a pathway for the
      biosynthesis of calcimycin and assign the genes to the biosynthesis steps. Our
      findings set the stage for producing much desired calcimycin derivatives using
      genetic modification instead of chemical synthesis.

PMID- 21173185
TI  - Analysis of low-frequency mutations associated with drug resistance to
      raltegravir before antiretroviral treatment.
AB  - Raltegravir is highly efficacious in the treatment of HIV-1 infection. The
      prevalence and impact on virologic outcome of low-frequency resistant mutations
      among HIV-1-infected patients not previously treated with raltegravir have not
      been fully established. Samples from HIV treatment-experienced patients entering
      a clinical trial of raltegravir treatment were analyzed using a parallel allele
      specific sequencing (PASS) assay that assessed six primary and six secondary
      integrase mutations. Patients who achieved and sustained virologic suppression
      (success patients, n = 36) and those who experienced virologic rebound (failure
      patients, n = 35) were compared. Patients who experienced treatment failure had
      twice as many raltegravir-associated resistance mutations prior to initiating
      treatment as those who achieved sustained virologic success, but the difference
      was not statistically significant. The frequency of nearly all detected
      resistance mutations was less than 1% of viral population, and the frequencies of
      mutations between the success and failure groups were similar. Expansion of pre
      existing mutations (one primary and five secondary) was observed in 16 treatment
      failure patients in whom minority resistant mutations were detected at baseline,
      suggesting that they might play a role in the development of drug resistance. Two
      or more mutations were found in 13 patients (18.3%), but multiple mutations were
      not present in any single viral genome by linkage analysis. Our study
      demonstrates that low-frequency primary RAL-resistant mutations were uncommon,
      while minority secondary RAL-resistant mutations were more frequently detected in
      patients naive to raltegravir. Additional studies in larger populations are
      warranted to fully understand the clinical implications of these mutations.

PMID- 21173187
TI  - Oxidative stress induction of the MexXY multidrug efflux genes and promotion of
      aminoglycoside resistance development in Pseudomonas aeruginosa.
AB  - Exposure to reactive oxygen species (ROS) (e.g., peroxide) was shown to induce
      expression of the PA5471 gene, which was previously shown to be required for
      antimicrobial induction of the MexXY components of the MexXY-OprM multidrug
      efflux system and aminoglycoside resistance determinant in Pseudomonas
      aeruginosa. mexXY was also induced by peroxide exposure, and this too was PA5471
      dependent. The prospect of ROS promoting mexXY expression and aminoglycoside
      resistance recalls P. aeruginosa infection of the chronically inflamed lungs of
      cystic fibrosis (CF) patients, where the organism is exposed to ROS and where
      MexXY-OprM predominates as the mechanism of aminoglycoside resistance. While ROS
      did not enhance aminoglycoside resistance in vitro, long-term (8-day) exposure of
      P. aeruginosa to peroxide (mimicking chronic in vivo ROS exposure) increased
      aminoglycoside resistance frequency, dependent upon PA5471 and mexXY. This
      enhanced resistance frequency was also seen in a mutant strain overexpressing
      PA5471, in the absence of peroxide, suggesting that induction of PA5471 by
      peroxide was key to peroxide enhancement of aminoglycoside resistance frequency.
      Resistant mutants selected following peroxide exposure were typically pan
      aminoglycoside-resistant, with mexXY generally required for this resistance.
      Moreover, PA5471 was required for mexXY expression and aminoglycoside resistance
      in these as well as several CF isolates examined.

PMID- 21173186
TI  - Systematic review and meta-analysis of the effectiveness and safety of
      tigecycline for treatment of infectious disease.
AB  - The aim of this study was to compare the efficacy and safety of tigecycline, a
      newly developed glycylcycline antibiotic, with those of empirical antibiotic
      regimens which have been reported to possess good efficacy for complicated skin
      and skin structure infections (cSSSIs), complicated intra-abdominal infections
      (cIAIs), community-acquired pneumonia (CAP), and other infections caused by
      methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant
      Enterococcus (VRE). A meta-analysis of randomized controlled trials (RCTs)
      identified in PubMed, the Cochrane Library, and Embase was performed. Eight RCTs
      involving 4,651 patients were included in the meta-analysis. Compared with
      therapy with empirical antibiotic regimens, tigecycline monotherapy was
      associated with similar clinical treatment success rates (for the clinically
      evaluable [CE] population, odds ratio [OR] = 0.92, 95% confidence interval [CI] =
      0.76 to 1.12, P = 0.42; for the clinical modified intent-to-treat [c-mITT]
      population, OR = 0.86, 95% CI = 0.74 to 1.01, P = 0.06) and similar
      microbiological treatment success rates (for the microbiologically evaluable [ME]
      population, OR = 0.86, 95% CI = 0.69 to 1.07, P = 0.19). The incidence of adverse
      events in the tigecycline group was significantly higher than that in the other
      therapy groups with a statistical margin (for the modified intent-to-treat [mITT]
      population, OR = 1.33, 95% CI = 1.17 to 1.52, P < 0.0001), especially in the
      digestive system (mITT population, OR = 2.41, 95% CI = 1.67 to 3.46, P <
      0.00001). No difference regarding all-cause mortality and drug-related mortality
      between tigecycline and the other regimens was found, although numerically higher
      mortality was found in the tigecycline group. This meta-analysis provides
      evidence that tigecycline monotherapy may be used as effectively as the
      comparison therapy for cSSSI, cIAIs, CAP, and infections caused by MRSA/VRE.
      However, because of the high risk of mortality, AEs, and emergence of resistant
      isolates, prudence with the clinical use of tigecycline monotherapy in infections
      is required.

PMID- 21173188
TI  - Darunavir, ritonavir, and etravirine pharmacokinetics in the cervicovaginal fluid
      and blood plasma of HIV-infected women.
AB  - We report darunavir, ritonavir, and etravirine pharmacokinetics in cervicovaginal
      fluid and blood plasma for women from the Gender, Race and Clinical Experience
      (GRACE) study. Eight women received darunavir-ritonavir (600/100 mg) twice daily
      (b.i.d.); two also received etravirine (200 mg) b.i.d. Week 4 paired blood plasma
      and cervicovaginal fluid samples were collected over 12 h. Darunavir and
      etravirine cervicovaginal fluid exposures were higher than blood plasma
      exposures; ritonavir cervicovaginal fluid exposure was lower than blood plasma
      exposure. The high exposures of darunavir and etravirine in cervicovaginal fluid
      warrant further evaluation of these drugs for use in HIV-1 prevention.

PMID- 21173189
TI  - Characterization of the Novel CMT Enzyme TEM-154.
AB  - TEM-154, identified in Portugal in 2004, associated the substitutions observed in
      the extended-spectrum beta-lactamase (ESBL) TEM-12 and in the inhibitor-resistant
      penicillinase (IRT) TEM-33. This enzyme exhibited hydrolytic activity against
      ceftazidime and a low level of resistance to clavulanic acid. Surprisingly, the
      substitution Met69Leu enhanced the catalytic efficiency of oxyimino beta-lactams
      conferred by the substitution Arg164Ser. Its discovery confirms the dissemination
      of the complex mutant group of TEM enzymes in European countries.

PMID- 21173190
TI  - Enzymatic activities of the human AGPAT isoform 3 and isoform 5: localization of
      AGPAT5 to mitochondria.
AB  - The enzyme 1-acylglycerol-3-phosphate-O-acyltransferase (AGPAT) converts
      lysophosphatidic acid (LPA) to phosphatidic acid (PA). In this study, we show
      enzymatic properties, tissue distribution, and subcellular localization of human
      AGPAT3 and AGPAT5. In cells overexpressing these isoforms, the proteins were
      detected in the nuclear envelope and the endoplasmic reticulum. AGPAT5-GFP fusion
      protein was localized in the mitochondria of both Chinese hamster ovary and human
      epithelial cervical cancer cells. Using lysates of AD293 cells infected with
      AGPAT3 and AGPAT5 recombinant adenovirus, we show that AGPAT3 and AGPAT5 proteins
      have AGPAT activity. Both the isoforms have similar apparent V(max) of 6.35 and
      2.42 nmol/min/mg protein, respectively, for similar LPA. The difference between
      the two isoforms is in their use of additional lysophospholipids. AGPAT3 shows
      significant esterification of lysophosphatidylinositol (LPI) in the presence of
      C20:4 fatty acid, whereas AGPAT5 demonstrates significant acyltransferase
      activity toward lysophosphatidylethanolamine (LPE) in the presence of C18:1 fatty
      acid. The AGPAT3 mRNA is ubiquitously expressed in human tissues with several
      fold differences in the expression pattern compared with the closely related
      AGPAT4. In summary, we show that in the presence of different fatty acids, AGPAT3
      and AGPAT5 prefer different lysophospholipids as acyl acceptors. More
      importantly, localization of overexpressed AGPAT5 (this study) as well as GPAT1
      and 2 (previous studies) in mitochondria supports the idea that the mitochondria
      might be capable of synthesizing some of their own glycerophospholipids.

PMID- 21173191
TI  - Arthroscopically pertinent landmarks for tunnel positioning in single-bundle and
      double-bundle anterior cruciate ligament reconstructions.
AB  - BACKGROUND: Quantification of the overall anterior cruciate ligament (ACL) and
      anteromedial (AM) and posterolateral (PL) bundle centers in respect to
      arthroscopically pertinent bony and soft tissue landmarks has not been thoroughly
      assessed. HYPOTHESIS: A standardized anatomical measurement method can quantitate
      the locations of the ACL and AM and PL bundle centers in reference to each other
      and anatomical landmarks. STUDY DESIGN: Descriptive laboratory study. METHODS:
      Quantification of the ACL and its bundle attachments was performed on 11
      cadaveric knees using a radio frequency-tracking device. RESULTS: The tibial ACL
      attachment center was 7.5 mm medial to the anterior horn of the lateral meniscus,
      13.0 mm anterior to the retro-eminence ridge, and 10.5 mm posterior to the ACL
      ridge. The femoral ACL attachment center was 1.7 mm proximal to the bifurcate
      ridge and 6.1 mm posterior to the lateral intercondylar ridge. The tibial AM
      attachment center was 8.3 mm medial to the anteromedial aspect of the lateral
      meniscus anterior horn, 17.8 mm anterior to the retro-eminence ridge, and 5.6 mm
      posterior to the ACL ridge. The femoral AM attachment center was 4.8 mm proximal
      to the bifurcate ridge and 7.1 mm posterior to the lateral intercondylar ridge.
      The tibial PL bundle attachment center was 6.6 mm medial to the posteromedial
      aspect of the lateral meniscus anterior horn, 10.8 mm anteromedial to the root
      attachment of the lateral meniscus posterior horn, and 8.4 mm anterior to the
      retro-eminence ridge. The femoral PL bundle attachment center was 5.2 mm distal
      to the bifurcate ridge and 3.6 mm posterior to the lateral intercondylar ridge.
      CONCLUSION: The authors developed a comprehensive compilation of measurements of
      arthroscopically pertinent bony and soft tissue landmarks that quantitate the ACL
      and its individual bundle attachment centers on the tibia and femur. CLINICAL
      RELEVANCE: These clinically relevant arthroscopic landmarks may enhance single-
      and double-bundle ACL reconstructions through improved tunnel placement.

PMID- 21173192
TI  - Management of medial-sided knee injuries, part 2: posteromedial corner.
AB  - Injury to the posteromedial corner (PMC) of the knee differs anatomically and
      biomechanically from isolated injury to the medial collateral ligament. Newer
      anatomic and biomechanical studies are refining the field's understanding of the
      medial side of the knee, as well as its role in multiple ligament injuries.
      Valgus instability places additional strain on a reconstructed anterior or
      posterior cruciate ligament, which can contribute to late graft failure. Injuries
      to the PMC may not heal without surgical repair or reconstruction, particularly
      when part of a multiple-ligament injury. Identification of PMC injury before
      cruciate reconstruction is important so that appropriate repair or reconstruction
      of the PMC and medial collateral ligament can be undertaken at the same time.
      This article reviews the relevant literature on the PMC, discusses reasons for
      selective operative management, and illustrates reconstructive strategies for PMC
      injuries occurring as part of a medial-sided or multiligament injury to the knee.

PMID- 21173193
TI  - Can the reparability of meniscal tears be predicted with magnetic resonance
      imaging?
AB  - BACKGROUND: Historically, magnetic resonance imaging (MRI) has been very useful
      in diagnosing meniscal tears but not as valuable in predicting whether a meniscal
      tear is reparable. Given that several recent studies suggested that MRI can be
      used to predict tear reparability, the topic has resurfaced as a controversy in
      the orthopaedic and radiology literatures. HYPOTHESIS: Experienced
      musculoskeletal radiologists can use MRI to predict the reparability of meniscal
      tears with good to excellent accuracy using the same arthroscopic criteria used
      by surgeons intraoperatively. STUDY DESIGN: Cohort study (diagnosis); Level of
      evidence, 3. METHODS: Fifty-eight patients with meniscal tears treated with
      repair were matched by age and sex with 61 patients with tears treated with
      meniscectomy. Two senior musculoskeletal radiologists independently and blindly
      reviewed preoperative MRI of these 119 meniscal tears. Using established
      arthroscopic criteria, the radiologists were asked to grade each tear 0 to 4,
      with 1 point for each of the following: a tear larger than 10 mm, within 3 mm of
      the meniscosynovial junction, greater than 50% thickness, and with an intact
      inner meniscal fragment. Only a tear with a score of 4 would be predicted to be
      reparable. RESULTS: The 2 radiologists' ability to correctly estimate
      reparability was poor, with 58.0% and 62.7% correct predictions (kappa = 0.155
      and 0.250, respectively). Interrater reliability assessment showed that the
      raters agreed on a score of 4 (reparable) versus <4 (not reparable) 73.7% of the
      time (kappa = 0.434) but came to identical scores only 38.1% of the time (kappa =
      0.156). Determining the status of the inner fragment was the most predictive
      individual criterion and the only one to reach statistical significance (chi(2) =
      14.9, P <.001). CONCLUSION: Magnetic resonance imaging is not an effective or
      efficient predictor of reparability of meniscal tears with the current
      arthroscopic criteria.

PMID- 21173194
TI  - Effect of shoulder abduction angle on biomechanical properties of the repaired
      rotator cuff tendons with 3 types of double-row technique.
AB  - BACKGROUND: After rotator cuff repair, the shoulder is immobilized in various
      abduction positions. However, there is no consensus on the proper abduction
      angle. PURPOSE: To assess the effect of shoulder abduction angle on the
      biomechanical properties of the repaired rotator cuff tendons among 3 types of
      double-row techniques. STUDY DESIGN: Controlled laboratory study. METHODS: Thirty
      two fresh-frozen porcine shoulders were used. A simulated rotator cuff tear was
      repaired by 1 of 3 double-row techniques: conventional double-row repair,
      transosseous-equivalent repair, and a combination of conventional double-row and
      bridging sutures (compression double-row repair). Each specimen underwent cyclic
      testing followed by tensile testing to failure at a simulated shoulder abduction
      angle of 0 degrees  or 40 degrees  on a material testing machine. Gap formation
      and failure loads were measured. RESULTS: Gap formation in conventional double
      row repair at 0 degrees  (1.2 +/- 0.5 mm) was significantly greater than that at
      40 degrees  (0.5 +/- 0.3mm, P = .01). The yield and ultimate failure loads for
      conventional double-row repair at 40 degrees  were significantly larger than
      those at 0 degrees  (P < .01), whereas those for transosseous-equivalent repair
      (P < .01) and compression double-row repair (P < .0001) at 0 degrees  were
      significantly larger than those at 40 degrees . The failure load for compression
      double-row repair was the greatest among the 3 double-row techniques at both 0
      degrees  and 40 degrees  of abduction. CONCLUSION: Bridging sutures have a
      greater effect on the biomechanical properties of the repaired rotator cuff
      tendon at a low abduction angle, and the conventional double-row technique has a
      greater effect at a high abduction angle. CLINICAL RELEVANCE: Proper abduction
      position after rotator cuff repair differs between conventional double-row repair
      and transosseous-equivalent repair. The authors recommend the use of the combined
      technique of conventional double-row and bridging sutures to obtain better
      biomechanical properties at both low and high abduction angles.

PMID- 21173195
TI  - Effect of tibial tunnel position on stability of the knee after anterior cruciate
      ligament reconstruction: is the tibial tunnel position most important?
AB  - BACKGROUND: Minimal attention has been directed toward tibial tunnel position and
      the native tibial anterior cruciate ligament (ACL) footprint. PURPOSE: To
      evaluate the effect of tibial tunnel position on restoration of knee kinematics
      and stability after ACL reconstruction. STUDY DESIGN: Controlled laboratory
      study. METHODS: Ten paired cadaveric knees were subjected to biomechanical
      testing (standardized Lachman and mechanized pivot-shift examination). With each
      maneuver, a computer-assisted navigation system recorded the 3-dimensional motion
      path of a tracked point at the center of the tibia, medial tibial plateau, and
      lateral tibial plateau. The testing protocol consisted of evaluation in the
      intact state and after complete ACL transection, after ACL transection with
      bilateral meniscectomy, and after ACL reconstruction using 3 tibial tunnel
      positions--over the top (OTT), anterior footprint (AT), and posterior footprint
      (PT)--with a standard femoral socket placed in the center of the femoral
      footprint. Repeated-measures analysis of variance with a post hoc Tukey test
      compared measured translations with each condition. RESULTS: A significant
      difference in anterior translation was seen with Lachman examination between the
      ACL-deficient condition and both the OTT and AT reconstructions, but no
      significant difference was observed between the ACL-deficient and PT
      reconstruction. The OTT and AT constructs were significantly better in limiting
      anterior translation of the lateral compartment compared with the PT ACL
      reconstruction during a pivot-shift maneuver in the ACL- and meniscal-deficient
      knee. However, anteriorizing the tibial position was accompanied by a
      correspondingly greater risk and magnitude of graft impingement in extension.
      CLINICAL RELEVANCE: The OTT and anterior tibial tunnel positions better control
      the Lachman and the pivot shift compared with an ACL graft placed in the
      posterior aspect of the tibial footprint. However, an anterior tibial tunnel
      position must be balanced against an increased risk and magnitude of graft
      impingement in extension.

PMID- 21173196
TI  - Surgical hip dislocation for the treatment of femoroacetabular impingement in
      high-level athletes.
AB  - BACKGROUND: Midterm outcome studies show that symptomatic femoroacetabular
      impingement (FAI) can be successfully treated by addressing the underlying
      pathomorphology with open or arthroscopic surgery. Although athletes may be
      vulnerable to hip injury from impingement, limited information is available
      regarding the results of open surgery in this group. HYPOTHESIS: High-level
      athletes with FAI can resume their sports after surgical hip dislocation and
      continue professional careers for a significant period. STUDY DESIGN: Case
      series; Level of evidence, 4. METHODS: Twenty-two professional male athletes
      (19.7 +/- 2.2 years) were evaluated by postal survey at a mean of 45.1 months
      (range, 12 to 79) after treatment by surgical hip dislocation (30 hips, cam- or
      mixed-type FAI; mean alpha angle, 69.3 degrees ; 14 ice hockey players).
      Evaluation included types and level of sports, subjective ratings, and CLINICAL
      OUTCOMES: Hip Outcome Score, SF-12, UCLA (University of California, Los Angeles)
      activity scale, Hip Sports Activity Scale, visual analog scale for pain. The
      primary outcome variable was return to professional sports; the clinical result
      was the secondary outcome variable. RESULTS: At follow-up, 21 of 22 patients
      (96%) were still competing professionally: 19 at their previous level and 2 in
      minor leagues. Eighteen (82%) were satisfied with their hip surgery and 19 (86%)
      with their sports ability. Mean activity levels were 9.8 per the UCLA scale and
      7.6 per the Hip Sports Activity Scale. Mean scores of the Hip Outcome Score
      Activities of Daily Living and Sport subscales were 94.5 and 89.1. Mean scores of
      the SF-12 physical and mental component summaries were 51.1 and 54.3. Pain levels
      during sports were 1.8 per the visual analog scale. CONCLUSION: Surgical hip
      dislocation for the treatment of FAI allows athletes to resume sports and
      continue professional careers at the same level for several years. Clinical
      outcomes in terms of subjective ratings and scores were favorable.

PMID- 21173197
TI  - Annular flexor pulley injuries in professional baseball pitchers: a case series.

PMID- 21173198
TI  - The national heart failure audit for England and Wales 2008-2009.
AB  - OBJECTIVES: To obtain national data on the clinical characteristics,
      investigation, management and outcome of patients hospitalised with a diagnosis
      of heart failure. METHOD: A survey was carried out of the first 10 patients
      hospitalised with a primary diagnosis of heart failure each month in 86 hospitals
      providing services for acute medical admissions in England and Wales from April
      2008 until March 2009. The main outcome measures were rates of investigations,
      treatments and specialist management, length of hospital stay and mortality.
      RESULTS: The 86 hospitals enrolled 6170 patients with a median age of 78 years
      (IQR 70-85 years), including 2639 (43%) women. At admission, only 30% of patients
      were breathless at rest, while 43% had peripheral oedema. Echocardiograms were
      recorded in 75% of patients and left ventricular ejection fraction (LVEF) was
      <=40% in 78%. Natriuretic peptides were rarely measured. Allowing for missing
      data, >90% of patients were treated with loop diuretics at discharge, 80% with
      ACE inhibitors or angiotensin receptor blockers, 50% with beta-blockers and 30%
      with aldosterone antagonists. Patients with an LVEF <40% were more likely to
      receive these agents. Median hospital stay was 9 days (IQR 5-17) and in-patient
      mortality was 12%. Patients admitted to general medicine rather than cardiology
      wards were more likely to die (HR=2.5, 95% CI 2.0 to 3.3, p<0.001) even after
      adjusting for differences (HR=1.9, 95% CI 1.5 to 2.5, p<0.001). Projected 1-year
      mortality below and above age 75 years was 26% and 56%, with higher rates if
      managed on general medicine rather than cardiology wards (HR=1.4, 95% CI 1.2 to
      1.6, p<0.001). CONCLUSION: The prognosis of patients hospitalised with heart
      failure remains poor and investigation and treatment suboptimal. Specialist
      services are associated with higher rates of investigation and treatment and
      improved outcome.

PMID- 21173199
TI  - Bidentate RNA-magnesium clamps: on the origin of the special role of magnesium in
      RNA folding.
AB  - Magnesium plays a special role in RNA function and folding. Although water is
      magnesium's most common first-shell ligand, the oxyanions of RNA have significant
      affinity for magnesium. Here we provide a quantum mechanical description of first
      shell RNA-magnesium and DNA-magnesium interactions, demonstrating the unique
      features that characterize the energetics and geometry of magnesium complexes
      within large folded RNAs. Our work focuses on bidentate chelation of magnesium by
      RNA or DNA, where multiple phosphate oxyanions enter the first coordination shell
      of magnesium. These bidentate RNA clamps of magnesium occur frequently in large
      RNAs. The results here suggest that magnesium, compared to calcium and sodium,
      has an enhanced ability to form bidentate clamps with RNA. Bidentate RNA-sodium
      clamps, in particular, are unstable and spontaneously open. Due to magnesium's
      size and charge density it binds more intimately than other cations to the
      oxyanions of RNA, so that magnesium clamps are stabilized not only by
      electrostatic interactions, but also by charge transfer, polarization, and
      exchange interactions. These nonelectrostatic components of the binding are quite
      substantial with the high charge and small interatomic distances within the
      magnesium complexes, but are less pronounced for calcium due to its larger size,
      and for sodium due to its smaller charge. Additionally, bidentate RNA clamps of
      magnesium are more stable than those with DNA. The source of the additional
      stability of RNA complexes is twofold: there is a slightly attenuated energetic
      penalty for ring closure in the formation of RNA bidentate chelation complexes
      and elevated electrostatic interactions between the RNA and cations. In sum, it
      can be seen why sodium and calcium cannot replicate the structures or energetics
      of RNA-magnesium complexes.

PMID- 21173200
TI  - Substrate recognition by ribonucleoprotein ribonuclease MRP.
AB  - The ribonucleoprotein complex ribonuclease (RNase) MRP is a site-specific
      endoribonuclease essential for the survival of the eukaryotic cell. RNase MRP
      closely resembles RNase P (a universal endoribonuclease responsible for the
      maturation of the 5' ends of tRNA) but recognizes distinct substrates including
      pre-rRNA and mRNA. Here we report the results of an in vitro selection of
      Saccharomyces cerevisiae RNase MRP substrates starting from a pool of random
      sequences. The results indicate that RNase MRP cleaves single-stranded RNA and is
      sensitive to sequences in the immediate vicinity of the cleavage site requiring a
      cytosine at the position +4 relative to the cleavage site. Structural
      implications of the differences in substrate recognition by RNases P and MRP are
      discussed.

PMID- 21173202
TI  - Antisepsis in the time of antibiotics: following in the footsteps of John Snow
      and Joseph Lister.

PMID- 21173203
TI  - Surgical site infections and the anesthesia professionals' microbiome: we've all
      been slimed! Now what are we going to do about it?

PMID- 21173201
TI  - Do the hairpin and VS ribozymes share a common catalytic mechanism based on
      general acid-base catalysis? A critical assessment of available experimental
      data.
AB  - The active centers of the hairpin and VS ribozymes are both generated by the
      interaction of two internal loops, and both ribozymes use guanine and adenine
      nucleobases to accelerate cleavage and ligation reactions. The centers are
      topologically equivalent and the relative positioning of key elements the same.
      There is good evidence that the cleavage reaction of the VS ribozyme is catalyzed
      by the guanine (G638) acting as general base and the adenine (A756) as general
      acid. We now critically evaluate the experimental mechanistic evidence for the
      hairpin ribozyme. We conclude that all the available data are fully consistent
      with a major contribution to catalysis by general acid-base catalysis involving
      the adenine (A38) and guanine (G8). It appears that the two ribozymes are
      mechanistically equivalent.

PMID- 21173204
TI  - Towards a better understanding of body mass index and patient outcomes.

PMID- 21173205
TI  - Prone to blindness: answers to postoperative visual loss.

PMID- 21173207
TI  - The efficacy and safety of colloid resuscitation in the critically ill.

PMID- 21173206
TI  - Intraoperative methadone: rediscovery, reappraisal, and reinvigoration?

PMID- 21173209
TI  - Choice of isotonic perioperative fluid in children.

PMID- 21173208
TI  - Guidelines for pediatric perioperative care during short-term plastic
      reconstructive surgical projects in less developed nations.

PMID- 21173210
TI  - Pediatric postoperative fluid therapy: avoiding hyponatremia.

PMID- 21173211
TI  - Point of care devices should not be relied upon for perioperative glucose
      measurement.

PMID- 21173212
TI  - The airway scope may be less effective for tracheal intubation under direct
      daylight in a prehospital environment.

PMID- 21173213
TI  - Continuous thermodilution cardiac output monitoring during therapeutic
      hypothermia.

PMID- 21173214
TI  - Do not withdraw stylets when advancing spinal needles.

PMID- 21173215
TI  - Let's end the error of the standard error.

PMID- 21173216
TI  - P values: a guide to uncertainty but not truth.

PMID- 21173217
TI  - Profile of Alexander S. Raikhel.

PMID- 21173218
TI  - Intracellular organelles mediate cytoplasmic pulling force for centrosome
      centration in the Caenorhabditis elegans early embryo.
AB  - The centrosome is generally maintained at the center of the cell. In animal
      cells, centrosome centration is powered by the pulling force of microtubules,
      which is dependent on cytoplasmic dynein. However, it is unclear how dynein
      brings the centrosome to the cell center, i.e., which structure inside the cell
      functions as a substrate to anchor dynein. Here, we provide evidence that a
      population of dynein, which is located on intracellular organelles and is
      responsible for organelle transport toward the centrosome, generates the force
      required for centrosome centration in Caenorhabditis elegans embryos. By using
      the database of full-genome RNAi in C. elegans, we identified dyrb-1, a dynein
      light chain subunit, as a potential subunit involved in dynein anchoring for
      centrosome centration. DYRB-1 is required for organelle movement toward the minus
      end of the microtubules. The temporal correlation between centrosome centration
      and the net movement of organelle transport was found to be significant.
      Centrosome centration was impaired when Rab7 and RILP, which mediate the
      association between organelles and dynein in mammalian cells, were knocked down.
      These results indicate that minus end-directed transport of intracellular
      organelles along the microtubules is required for centrosome centration in C.
      elegans embryos. On the basis of this finding, we propose a model in which the
      reaction forces of organelle transport generated along microtubules act as a
      driving force that pulls the centrosomes toward the cell center. This is the
      first model, to our knowledge, providing a mechanical basis for cytoplasmic
      pulling force for centrosome centration.

PMID- 21173219
TI  - Relative roles of climatic suitability and anthropogenic influence in determining
      the pattern of spread in a global invader.
AB  - Because invasive species threaten the integrity of natural ecosystems, a major
      goal in ecology is to develop predictive models to determine which species may
      become widespread and where they may invade. Indeed, considerable progress has
      been made in understanding the factors that influence the local pattern of spread
      for specific invaders and the factors that are correlated with the number of
      introduced species that have become established in a given region. However, few
      studies have examined the relative importance of multiple drivers of invasion
      success for widespread species at global scales. Here, we use a dataset of >5,000
      presence/absence records to examine the interplay between climatic suitability,
      biotic resistance by native taxa, human-aided dispersal, and human modification
      of habitats, in shaping the distribution of one of the world's most notorious
      invasive species, the Argentine ant (Linepithema humile). Climatic suitability
      and the extent of human modification of habitats are primarily responsible for
      the distribution of this global invader. However, we also found some evidence for
      biotic resistance by native communities. Somewhat surprisingly, and despite the
      often cited importance of propagule pressure as a crucial driver of invasions,
      metrics of the magnitude of international traded commodities among countries were
      not related to global distribution patterns. Together, our analyses on the global
      scale distribution of this invasive species provide strong evidence for the
      interplay of biotic and abiotic determinants of spread and also highlight the
      challenges of limiting the spread and subsequent impact of highly invasive
      species.

PMID- 21173221
TI  - Non-ATG-initiated translation directed by microsatellite expansions.
AB  - Trinucleotide expansions cause disease by both protein- and RNA-mediated
      mechanisms. Unexpectedly, we discovered that CAG expansion constructs express
      homopolymeric polyglutamine, polyalanine, and polyserine proteins in the absence
      of an ATG start codon. This repeat-associated non-ATG translation (RAN
      translation) occurs across long, hairpin-forming repeats in transfected cells or
      when expansion constructs are integrated into the genome in lentiviral-transduced
      cells and brains. Additionally, we show that RAN translation across human
      spinocerebellar ataxia type 8 (SCA8) and myotonic dystrophy type 1 (DM1) CAG
      expansion transcripts results in the accumulation of SCA8 polyalanine and DM1
      polyglutamine expansion proteins in previously established SCA8 and DM1 mouse
      models and human tissue. These results have implications for understanding
      fundamental mechanisms of gene expression. Moreover, these toxic, unexpected,
      homopolymeric proteins now should be considered in pathogenic models of
      microsatellite disorders.

PMID- 21173220
TI  - Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT
      and PDGFRA mutations.
AB  - Carney-Stratakis syndrome, an inherited condition predisposing affected
      individuals to gastrointestinal stromal tumor (GIST) and paraganglioma, is caused
      by germline mutations in succinate dehydrogenase (SDH) subunits B, C, or D,
      leading to dysfunction of complex II of the electron transport chain. We
      evaluated the role of defective cellular respiration in sporadic GIST lacking
      mutations in KIT or PDGFRA (WT). Thirty-four patients with WT GIST without a
      personal or family history of paraganglioma were tested for SDH germline
      mutations. WT GISTs lacking demonstrable SDH genetic inactivation were evaluated
      for SDHB expression by immunohistochemistry and Western blotting and for complex
      II activity. For comparison, SDHB expression was also determined in KIT mutant
      and neurofibromatosis-1-associated GIST, and complex II activity was also
      measured in SDH-deficient paraganglioma and KIT mutant GIST; 4 of 34 patients
      (12%) with WT GIST without a personal or family history of paraganglioma had
      germline mutations in SDHB or SDHC. WT GISTs lacking somatic mutations or
      deletions in SDH subunits had either complete loss of or substantial reduction in
      SDHB protein expression, whereas most KIT mutant GISTs had strong SDHB
      expression. Complex II activity was substantially decreased in WT GISTs. WT
      GISTs, particularly those in younger patients, have defects in SDH mitochondrial
      complex II, and in a subset of these patients, GIST seems to arise from germline
      inactivating SDH mutations. Testing for germline mutations in SDH is recommended
      in patients with WT GIST. These findings highlight a potential central role of
      SDH dysregulation in WT GIST oncogenesis.

PMID- 21173222
TI  - Epstein-Barr virus nuclear antigen 3C regulated genes in lymphoblastoid cell
      lines.
AB  - EBV nuclear antigen 3C (EBNA3C) is an essential transcription factor for EBV
      transformed lymphoblast cell line (LCL) growth. To identify EBNA3C-regulated
      genes in LCLs, microarrays were used to measure RNA abundances in each of three
      different LCLs that conditionally express EBNA3C fused to a 4-OH-Tamoxifen
      dependent estrogen receptor hormone binding domain (EBNA3CHT). At least three
      RNAs were assayed for each EBNA3CHT LCL under nonpermissive conditions,
      permissive conditions, and nonpermissive conditions with wild-type EBNA3C
      transcomplementation. Using a two-way ANOVA model of EBNA3C levels, we identified
      550 regulated genes that were at least 1.5-fold up- or down-regulated with false
      discovery rates < 0.01. EBNA3C-regulated genes overlapped significantly with
      genes regulated by EBNA2 and EBNA3A consistent with coordinated effects on cell
      gene transcription. Of the 550 EBNA3C-regulated genes, 106 could be placed in
      protein networks. A seeded Bayesian network analysis of the 80 most significant
      EBNA3C-regulated genes suggests that RAC1, LYN, and TNF are upstream of other
      EBNA3C-regulated genes. Gene set enrichment analysis found enrichment for MAP
      kinase signaling, cytokine-cytokine receptor interactions, JAK-STAT signaling,
      and cell adhesion molecules, implicating these pathways in EBNA3C effects on LCL
      growth or survival. EBNA3C significantly up-regulated the CXCL12 ligand and its
      CXCR4 receptor and increased LCL migration. CXCL12 up-regulation depended on
      EBNA3C's interaction with the cell transcription factor, RBPJ, which is essential
      for LCL growth. EBNA3C also up-regulated MYC 1.3-fold and down-regulated CDKN2A
      exons 2 and 3, shared by p16 and p14, 1.4-fold, with false discovery rates < 5 *
      10(-4).

PMID- 21173223
TI  - C-X-C receptor type 4 promotes metastasis by activating p38 mitogen-activated
      protein kinase in myeloid differentiation antigen (Gr-1)-positive cells.
AB  - Increasing evidence suggests that myeloid bone marrow-derived cells (BMDCs) play
      a critical role in lung metastasis. Blockade of VEGF receptor 1 (VEGFR1) has been
      proposed as a potential strategy to limit myeloid BMDC recruitment to tumors.
      However, preclinical evidence indicates that this strategy may not be effective
      in all tumors. Thus, establishing which molecular mechanisms are responsible for
      the "escape" of these BMDCs from VEGFR1 inhibition would facilitate development
      of strategies to control metastasis. Here, we report the complementary role of
      the chemokine (C-X-C motif) ligand 12/C-X-C chemokine receptor 4 (CXCR4) and
      VEGF/VEGFR1 pathways in promoting lung metastasis in mice via BMDC recruitment
      using chimeric mice with deficiency in CXCR4 and VEGFR1-tyrosine kinase in the
      BMDCs. We first demonstrate that CXCR4 activity is essential for recruitment of
      myeloid differentiation antigen (Gr-1)-positive BMDCs, whereas VEGFR1 activity is
      responsible for macrophage recruitment in established tumors. Inhibition of both
      VEGFR1 and CXCR4 signaling in myeloid BMDCs exerted greater effects on tumor
      vascular density, growth, and lung metastasis than inhibition of VEGFR1 alone.
      These effects were reproduced after pharmacologic inhibition of CXCR4 with
      AMD3100. VEGFR1 and CXCR4 independently exerted a promigratory effect in myeloid
      BMDCs by activating p38 mitogen-activating protein kinase. Thus, combining CXCR4
      blockade with inhibition of VEGFR1 may induce greater tumor growth delay and
      prevent or inhibit metastasis.

PMID- 21173224
TI  - Regulation of synaptic stability by AMPA receptor reverse signaling.
AB  - The establishment of neuronal circuits relies on the stabilization of
      functionally appropriate connections and the elimination of inappropriate ones.
      Here we report that postsynaptic AMPA receptors play a critical role in
      regulating the stability of glutamatergic synapses. Removal of surface AMPA
      receptors leads to a decrease in the number and stability of excitatory
      presynaptic inputs, whereas overexpression increases synapse number and
      stability. Furthermore, overexpression of AMPA receptors along with Neuroligin-1
      in 293T cells is sufficient to stabilize presynaptic inputs from cortical neurons
      onto heterologous cells. The stabilization of presynaptic inputs by AMPA
      receptors is not dependent on receptor-mediated current and instead relies on
      structural interactions mediated by the N-terminal domain of the glutamate
      receptor 2 (GluR2) subunit. These observations indicate that transsynaptic
      signaling mediated by the extracellular domain of GluR2 regulates the stability
      of presynaptic terminals.

PMID- 21173225
TI  - Calcium-dependent activator protein for secretion 2 (CAPS2) promotes BDNF
      secretion and is critical for the development of GABAergic interneuron network.
AB  - Calcium-dependent activator protein for secretion 2 (CAPS2) is a dense-core
      vesicle-associated protein that is involved in the secretion of BDNF. BDNF has a
      pivotal role in neuronal survival and development, including the development of
      inhibitory neurons and their circuits. However, how CAPS2 affects BDNF secretion
      and its biological significance in inhibitory neurons are largely unknown. Here
      we reveal the role of CAPS2 in the regulated secretion of BDNF and show the
      effect of CAPS2 on the development of hippocampal GABAergic systems. We show that
      CAPS2 is colocalized with BDNF, both synaptically and extrasynaptically in axons
      of hippocampal neurons. Overexpression of exogenous CAPS2 in hippocampal neurons
      of CAPS2-KO mice enhanced depolarization-induced BDNF exocytosis events in terms
      of kinetics, frequency, and amplitude. We also show that in the CAPS2-KO
      hippocampus, BDNF secretion is reduced, and GABAergic systems are impaired,
      including a decreased number of GABAergic neurons and their synapses, a decreased
      number of synaptic vesicles in inhibitory synapses, and a reduced frequency and
      amplitude of miniature inhibitory postsynaptic currents. Conversely, excitatory
      neurons in the CAPS2-KO hippocampus were largely unaffected with respect to field
      excitatory postsynaptic potentials, miniature excitatory postsynaptic currents,
      and synapse number and morphology. Moreover, CAPS2-KO mice exhibited several GABA
      system-associated deficits, including reduced late-phase long-term potentiation
      at CA3-CA1 synapses, decreased hippocampal theta oscillation frequency, and
      increased anxiety-like behavior. Collectively, these results suggest that CAPS2
      promotes activity-dependent BDNF secretion during the postnatal period that is
      critical for the development of hippocampal GABAergic networks.

PMID- 21173226
TI  - Cardiomyocytes from phorbol myristate acetate-activated mesenchymal stem cells
      restore electromechanical function in infarcted rat hearts.
AB  - Despite the safety and feasibility of mesenchymal stem cell (MSC) therapy, an
      optimal cell type has not yet emerged in terms of electromechanical integration
      in infarcted myocardium. We found that poor to moderate survival benefits of MSC
      implanted rats were caused by incomplete electromechanical integration induced by
      tissue heterogeneity between myocytes and engrafted MSCs in the infarcted
      myocardium. Here, we report the development of cardiogenic cells from rat MSCs
      activated by phorbol myristate acetate, a PKC activator, that exhibited high
      expressions of cardiac-specific markers and Ca(2+) homeostasis-related proteins
      and showed adrenergic receptor signaling by norepinephrine. Histological analysis
      showed high connexin 43 coupling, few inflammatory cells, and low fibrotic
      markers in myocardium implanted with these phorbol myristate acetate-activated
      MSCs. Infarct hearts implanted with these cells exhibited restoration of
      conduction velocity through decreased tissue heterogeneity and improved
      myocardial contractility. These findings have major implications for the
      development of better cell types for electromechanical integration of cell-based
      treatment for infarcted myocardium.

PMID- 21173227
TI  - Socioeconomic legacy yields an invasion debt.
AB  - Globalization and economic growth are widely recognized as important drivers of
      biological invasions. Consequently, there is an increasing need for governments
      to address the role of international trade in their strategies to prevent species
      introductions. However, many of the most problematic alien species are not recent
      arrivals but were introduced several decades ago. Hence, current patterns of
      alien-species richness may better reflect historical rather than contemporary
      human activities, a phenomenon which might be called "invasion debt." Here, we
      show that across 10 taxonomic groups (vascular plants, bryophytes, fungi, birds,
      mammals, reptiles, amphibians, fish, terrestrial insects, and aquatic
      invertebrates) in 28 European countries, current numbers of alien species
      established in the wild are indeed more closely related to indicators of
      socioeconomic activity from the year 1900 than to those from 2000, although the
      majority of species introductions occurred during the second half of the 20th
      century. The strength of the historical signal varies among taxonomic groups,
      with those possessing good capabilities for dispersal (birds, insects) more
      strongly associated with recent socioeconomic drivers. Nevertheless, our results
      suggest a considerable historical legacy for the majority of the taxa analyzed.
      The consequences of the current high levels of socioeconomic activity on the
      extent of biological invasions will thus probably not be completely realized
      until several decades into the future.

PMID- 21173228
TI  - Regulation of GABAergic synapse formation and plasticity by GSK3beta-dependent
      phosphorylation of gephyrin.
AB  - Postsynaptic scaffolding proteins ensure efficient neurotransmission by anchoring
      receptors and signaling molecules in synapse-specific subcellular domains. In
      turn, posttranslational modifications of scaffolding proteins contribute to
      synaptic plasticity by remodeling the postsynaptic apparatus. Though these
      mechanisms are operant in glutamatergic synapses, little is known about
      regulation of GABAergic synapses, which mediate inhibitory transmission in the
      CNS. Here, we focused on gephyrin, the main scaffolding protein of GABAergic
      synapses. We identify a unique phosphorylation site in gephyrin, Ser270, targeted
      by glycogen synthase kinase 3beta (GSK3beta) to modulate GABAergic transmission.
      Abolishing Ser270 phosphorylation increased the density of gephyrin clusters and
      the frequency of miniature GABAergic postsynaptic currents in cultured
      hippocampal neurons. Enhanced, phosphorylation-dependent gephyrin clustering was
      also induced in vitro and in vivo with lithium chloride. Lithium is a GSK3beta
      inhibitor used therapeutically as mood-stabilizing drug, which underscores the
      relevance of this posttranslational modification for synaptic plasticity.
      Conversely, we show that gephyrin availability for postsynaptic clustering is
      limited by Ca(2+)-dependent gephyrin cleavage by the cysteine protease calpain-1.
      Together, these findings identify gephyrin as synaptogenic molecule regulating
      GABAergic synaptic plasticity, likely contributing to the therapeutic action of
      lithium.

PMID- 21173229
TI  - RNA editing enzyme adenosine deaminase is a restriction factor for controlling
      measles virus replication that also is required for embryogenesis.
AB  - Measles virus (MV), a member of the family Paramyxoviridae and an exclusively
      human pathogen, is among the most infectious viruses. A progressive fatal
      neurodegenerative complication, subacute sclerosing panencephalitis (SSPE),
      occurs during persistent MV infection of the CNS and is associated with biased
      hypermutations of the viral genome. The observed hypermutations of A-to-G are
      consistent with conversions catalyzed by the adenosine deaminase acting on RNA
      (ADAR1). To evaluate the role of ADAR1 in MV infection, we selectively disrupted
      expression of the IFN-inducible p150 ADAR1 isoform and found it caused embryonic
      lethality at embryo day (E) 11-E12. We therefore generated p150-deficient and WT
      mouse embryo fibroblast (MEF) cells stably expressing the MV receptor signaling
      lymphocyte activation molecule (SLAM or CD150). The p150(-/-) but not WT MEF
      cells displayed extensive syncytium formation and cytopathic effect (CPE)
      following infection with MV, consistent with an anti-MV role of the p150 isoform
      of ADAR1. MV titers were 3 to 4 log higher in p150(-/-) cells compared with WT
      cells at 21 h postinfection, and restoration of ADAR1 in p150(-/-) cells
      prevented MV cytopathology. In contrast to infection with MV, p150 disruption had
      no effect on vesicular stomatitis virus, reovirus, or lymphocytic
      choriomeningitis virus replication but protected against CPE resulting from
      infection with Newcastle disease virus, Sendai virus, canine distemper virus, and
      influenza A virus. Thus, ADAR1 is a restriction factor in the replication of
      paramyxoviruses and orthomyxoviruses.

PMID- 21173230
TI  - Neurogenin3 inhibits proliferation in endocrine progenitors by inducing Cdkn1a.
AB  - During organogenesis, the final size of mature cell populations depends on their
      rates of differentiation and expansion. Because transient expression of
      Neurogenin3 (Neurog3) in progenitor cells in the developing pancreas initiates
      their differentiation to mature islet cells, we examined the role of Neurog3 in
      cell cycle control during this process. We found that mitotically active
      pancreatic progenitor cells in mouse embryos exited the cell cycle after the
      initiation of Neurog3 expression. Transcriptome analysis demonstrated that the
      Neurog3-expressing cells dramatically up-regulated the mRNA encoding cyclin
      dependent kinase inhibitor 1a (Cdkn1a). In Neurog3 null mice, the islet
      progenitor cells failed to activate Cdkn1a expression and continued to
      proliferate, showing that their exit from the cell cycle requires Neurog3.
      Furthermore, induced transgenic expression of Neurog3 in mouse beta-cells in vivo
      markedly decreased their proliferation, increased Cdkn1a levels, and eventually
      caused profound hyperglycemia. In contrast, in Cdkn1a null mice, proliferation
      was incompletely suppressed in the Neurog3-expressing cells. These studies reveal
      a crucial role for Neurog3 in regulating the cell cycle during the
      differentiation of islet cells and demonstrate that the subsequent down
      regulation of Neurog3 allows the mature islet cell population to expand.

PMID- 21173231
TI  - Receptor-type guanylate cyclase is required for carbon dioxide sensation by
      Caenorhabditis elegans.
AB  - CO(2) is both a critical regulator of animal physiology and an important sensory
      cue for many animals for host detection, food location, and mate finding. The
      free-living soil nematode Caenorhabditis elegans shows CO(2) avoidance behavior,
      which requires a pair of ciliated sensory neurons, the BAG neurons. Using in vivo
      calcium imaging, we show that CO(2) specifically activates the BAG neurons and
      that the CO(2)-sensing function of BAG neurons requires TAX-2/TAX-4 cyclic
      nucleotide-gated ion channels and the receptor-type guanylate cyclase GCY-9. Our
      results delineate a molecular pathway for CO(2) sensing and suggest that
      activation of a receptor-type guanylate cyclase is an evolutionarily conserved
      mechanism by which animals detect environmental CO(2).

PMID- 21173232
TI  - Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling
      intestinal stem cells.
AB  - The intestinal epithelium is maintained by a population of rapidly cycling
      (Lgr5(+)) intestinal stem cells (ISCs). It has been postulated, however, that
      slowly cycling ISCs must also be present in the intestine to protect the genome
      from accumulating deleterious mutations and to allow for a response to tissue
      injury. Here, we identify a subpopulation of slowly cycling ISCs marked by mouse
      telomerase reverse transcriptase (mTert) expression that can give rise to Lgr5(+)
      cells. mTert-expressing cells distribute in a pattern along the crypt-villus axis
      similar to long-term label-retaining cells (LRCs) and are resistant to tissue
      injury. Lineage-tracing studies demonstrate that mTert(+) cells give rise to all
      differentiated intestinal cell types, persist long term, and contribute to the
      regenerative response following injury. Consistent with other highly regenerative
      tissues, our results demonstrate that a slowly cycling stem cell population
      exists within the intestine.

PMID- 21173234
TI  - A network model for plant-pollinator community assembly.
AB  - Community assembly models, usually constructed for food webs, are an important
      component of our understanding of how ecological communities are formed. However,
      models for mutualistic community assembly are still needed, especially because
      these communities are experiencing significant anthropogenic disturbances that
      affect their biodiversity. Here, we present a unique network model that simulates
      the colonization and extinction process of mutualistic community assembly. We
      generate regional source pools of species interaction networks on the basis of
      statistical properties reported in the literature. We develop a dynamic
      synchronous Boolean framework to simulate, with few free parameters, the dynamics
      of new mutualistic community formation from the regional source pool. This
      approach allows us to deterministically map out every possible trajectory of
      community formation. This level of detail is rarely observed in other analytic
      approaches and allows for thorough analysis of the dynamical properties of
      community formation. As for food web assembly, we find that the number of stable
      communities is quite low, and the composition of the source pool influences the
      abundance and nature of community outcomes. However, in contrast to food web
      assembly, stable mutualistic communities form rapidly. Small communities with
      minor fluctuations in species presence/absence (self-similar limit cycles) are
      the most common community outcome. The unique application of this Boolean network
      approach to the study of mutualistic community assembly offers a great
      opportunity to improve our understanding of these critical communities.

PMID- 21173233
TI  - Critical role of PI3K signaling for NF-kappaB-dependent survival in a subset of
      activated B-cell-like diffuse large B-cell lymphoma cells.
AB  - The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL)
      represents a very aggressive human lymphoma entity. Constitutive NF-kappaB
      activation caused by chronic active B-cell receptor (BCR) signaling is common
      feature of many ABC DLBCL cells; however, the pathways linking BCR signaling to
      the NF-kappaB prosurvival network are largely unknown. Here we report that
      constitutive activity of PI3K and the downstream kinase PDK1 are essential for
      the viability of two ABC DLBCL cell lines that carry mutations in the BCR
      proximal signaling adaptor CD79B. In these cells, PI3K inhibition reduces NF
      kappaB activity and decreases the expression of NF-kappaB target genes.
      Furthermore, PI3K and PDK1 are required for maintaining MALT1 protease activity,
      which promotes survival of the affected ABC DLBCL cells. These results
      demonstrate a critical function of PI3K-PDK1 signaling upstream of MALT1 protease
      and NF-kappaB in distinct ABC DLBCL cells and provide a rationale for the
      pharmacologic use of PI3K inhibitors in DLBCL therapy.

PMID- 21173235
TI  - Children with autism are neither systematic nor optimal foragers.
AB  - It is well established that children with autism often show outstanding visual
      search skills. To date, however, no study has tested whether these skills,
      usually assessed on a table-top or computer, translate to more true-to-life
      settings. One prominent account of autism, Baron-Cohen's "systemizing" theory,
      gives us good reason to suspect that they should. In this study, we tested
      whether autistic children's exceptional skills at small-scale search extend to a
      large-scale environment and, in so doing, tested key claims of the systemizing
      account. Twenty school-age children with autism and 20 age- and ability-matched
      typical children took part in a large-scale search task in the "foraging room": a
      purpose-built laboratory, with numerous possible search locations embedded into
      the floor. Children were instructed to search an array of 16 (green) locations to
      find the hidden (red) target as quickly as possible. The distribution of target
      locations was manipulated so that they appeared on one side of the midline for
      80% of trials. Contrary to predictions of the systemizing account, autistic
      children's search behavior was much less efficient than that of typical children:
      they showed reduced sensitivity to the statistical properties of the search
      array, and furthermore, their search patterns were strikingly less optimal and
      less systematic. The nature of large-scale search behavior in autism cannot
      therefore be explained by a facility for systemizing. Rather, children with
      autism showed difficulties exploring and exploiting the large-scale space, which
      might instead be attributed to constraints (rather than benefits) in their
      cognitive repertoire.

PMID- 21173236
TI  - Reversing cocaine-induced synaptic potentiation provides enduring protection from
      relapse.
AB  - Cocaine addiction remains without an effective pharmacotherapy and is
      characterized by an inability of addicts to inhibit relapse to drug use.
      Vulnerability to relapse arises from an enduring impairment in cognitive control
      of motivated behavior, manifested in part by dysregulated synaptic potentiation
      and extracellular glutamate homeostasis in the projection from the prefrontal
      cortex to the nucleus accumbens. Here we show in rats trained to self-administer
      cocaine that the enduring cocaine-induced changes in synaptic potentiation and
      glutamate homeostasis are mechanistically linked through group II metabotropic
      glutamate receptor signaling. The enduring cocaine-induced changes in measures of
      cortico-accumbens synaptic and glial transmission were restored to predrug
      parameters for at least 2 wk after discontinuing chronic treatment with the
      cystine prodrug, N-acetylcysteine. N-acetylcysteine produced these changes by
      inducing an enduring restoration of nonsynaptic glutamatergic tone onto
      metabotropic glutamate receptors. The long-lasting pharmacological restoration of
      cocaine-induced glutamatergic adaptations by chronic N-acetylcysteine also caused
      enduring inhibition of cocaine-seeking in an animal model of relapse. These data
      mechanistically link nonsynaptic glutamate to cocaine-induced adaptations in
      excitatory transmission and demonstrate a mechanism to chronically restore
      prefrontal to accumbens transmission and thereby inhibit relapse in an animal
      model.

PMID- 21173237
TI  - Therapeutically targeting cyclin D1 in primary tumors arising from loss of Ini1.
AB  - Rhabdoid tumors (RTs) are rare, highly aggressive pediatric malignancies with
      poor prognosis and with no standard or effective treatment strategies. RTs are
      characterized by biallelic inactivation of the INI1 tumor suppressor gene. INI1
      directly represses CCND1 and activates cyclin-dependent kinase (cdk) inhibitors
      p16(Ink4a) and p21(CIP). RTs are exquisitely dependent on cyclin D1 for genesis
      and survival. To facilitate translation of unique therapeutic strategies, we have
      used genetically engineered, Ini1(+/-) mice for therapeutic testing. We found
      that PET can be used to noninvasively and accurately detect primary tumors in
      Ini1(+/-) mice. In a PET-guided longitudinal study, we found that treating
      Ini1(+/-) mice bearing primary tumors with the pan-cdk inhibitor flavopiridol
      resulted in complete and stable regression of some tumors. Other tumors showed
      resistance to flavopiridol, and one of the resistant tumors overexpressed cyclin
      D1, more than flavopiridol-sensitive cells. The concentration of flavopiridol
      used was not sufficient to down-modulate the high level of cyclin D1 and failed
      to induce cell death in the resistant cells. Furthermore, FISH and PCR analyses
      indicated that there is aneuploidy and increased CCND1 copy number in resistant
      cells. These studies indicate that resistance to flavopiridol may be correlated
      to elevated cyclin D1 levels. Our studies also indicate that Ini1(+/-) mice are
      valuable tools for testing unique therapeutic strategies and for understanding
      mechanisms of drug resistance in tumors that arise owing to loss of Ini1, which
      is essential for developing effective treatment strategies against these
      aggressive tumors.

PMID- 21173238
TI  - Identification of inducible brown adipocyte progenitors residing in skeletal
      muscle and white fat.
AB  - Brown fat is specialized for energy expenditure and has therefore been proposed
      to function as a defense against obesity. Despite recent advances in delineating
      the transcriptional regulation of brown adipocyte differentiation, cellular
      lineage specification and developmental cues specifying brown-fat cell fate
      remain poorly understood. In this study, we identify and isolate a subpopulation
      of adipogenic progenitors (Sca-1(+)/CD45(-)/Mac1(-); referred to as Sca-1(+)
      progenitor cells, ScaPCs) residing in murine brown fat, white fat, and skeletal
      muscle. ScaPCs derived from different tissues possess unique molecular expression
      signatures and adipogenic capacities. Importantly, although the ScaPCs from
      interscapular brown adipose tissue (BAT) are constitutively committed brown-fat
      progenitors, Sca-1(+) cells from skeletal muscle and subcutaneous white fat are
      highly inducible to differentiate into brown-like adipocytes upon stimulation
      with bone morphogenetic protein 7 (BMP7). Consistent with these findings, human
      preadipocytes isolated from subcutaneous white fat also exhibit the greatest
      inducible capacity to become brown adipocytes compared with cells isolated from
      mesenteric or omental white fat. When muscle-resident ScaPCs are re-engrafted
      into skeletal muscle of syngeneic mice, BMP7-treated ScaPCs efficiently develop
      into adipose tissue with brown fat-specific characteristics. Importantly, ScaPCs
      from obesity-resistant mice exhibit markedly higher thermogenic capacity compared
      with cells isolated from obesity-prone mice. These data establish the molecular
      characteristics of tissue-resident adipose progenitors and demonstrate a dynamic
      interplay between these progenitors and inductive signals that act in concert to
      specify brown adipocyte development.

PMID- 21173239
TI  - Single dose of anti-CTLA-4 enhances CD8+ T-cell memory formation, function, and
      maintenance.
AB  - CTLA-4, an Ig superfamily molecule with homology to CD28, is one of the most
      potent negative regulators of T-cell responses. In vivo blockade of CTLA-4
      exacerbates autoimmunity, enhances tumor-specific T-cell responses, and may
      inhibit the induction of T-cell anergy. Clinical trials of CTLA-4-blocking
      antibodies to augment T-cell responses to malignant melanoma are at an advanced
      stage; however, little is known about the effects of CTLA-4 blockade on memory
      CD8(+) T-cell responses and the formation and maintenance of long-term CD8(+) T
      cell memory. In our studies, we show that during in vivo memory CD8(+) T-cell
      responses to Listeria monocytogenes infection, CTLA-4 blockade enhances bacterial
      clearance and increases memory CD8(+) T-cell expansion. This is followed by an
      accumulation of memory cells that are capable of producing the effector cytokines
      IFN-gamma and TNF-alpha. We also demonstrate that in a vaccination setting,
      blocking CTLA-4 during CD8(+) T-cell priming leads to increased expansion and
      maintenance of antigen-specific memory CD8(+) T cells without adversely affecting
      the overall T-cell repertoire. This leads to an increase in memory cell effector
      function and improved protective immunity against further bacterial challenges.
      These results indicate that transient blockade of CTLA-4 enhances memory CD8(+) T
      cell responses and support the possible use of CTLA-4-blocking antibodies during
      vaccination to augment memory formation and maintenance.

PMID- 21173240
TI  - Abl-interactor-1 (Abi1) has a role in cardiovascular and placental development
      and is a binding partner of the alpha4 integrin.
AB  - Dynamic signals linking the actin cytoskeleton and cell adhesion receptors are
      essential for morphogenesis during development and normal tissue homeostasis.
      Abi1 is a central regulator of actin polymerization through interactions with
      multiple protein complexes. However, the in vivo role of Abi1 remains to be
      defined. The alpha4 integrin adhesion receptor is associated with enhanced
      protrusive activity and regulation of directional cell migration. Among integrin
      subunits, alpha4 exhibits unique properties in that it predominantly accumulates
      at the leading edge of migrating cells; however, the pathways that link the actin
      regulatory machinery to alpha4 at the leading edge have remained elusive. We
      generated Abi1 KO mice and found that loss of Abi1 phenocopies KO of alpha4. Mice
      lacking Abi1 or alpha4 exhibit midgestational lethality with abnormalities in
      placental and cardiovascular development. Notably, purified Abi1 protein binds
      directly to the alpha4 cytoplasmic tail and endogenous Abi1 colocalizes with
      phosphorylated alpha4 at the leading edge of spreading cells. Moreover, Abi1
      deficient cells expressing alpha4 have impaired cell spreading, which is rescued
      by WT Abi1 but not an Abi1 mutant lacking the alpha4-binding site. These data
      reveal a direct link between the alpha4 integrin and actin polymerization and
      uncover a role for Abi1 in the regulation of morphogenesis in vivo. The Abi1
      alpha4 interaction establishes a mechanistic paradigm for signaling between
      adhesion events and enhanced actin polymerization at the earliest stages of
      protrusion.

PMID- 21173242
TI  - Critical coordination of innate immune defense against Toxoplasma gondii by
      dendritic cells responding via their Toll-like receptors.
AB  - Toll-like receptors (TLRs) play an important role in host defense against a
      variety of microbial pathogens. We addressed the mechanism by which TLRs
      contribute to host defense against the lethal parasite Toxoplasma gondii by using
      mice with targeted inactivation of the TLR adaptor protein myeloid
      differentiation primary response gene 88 (MyD88) in different innate cell types.
      Lack of MyD88 in dendritic cells (DCs), but not in macrophages or neutrophils,
      resulted in high susceptibility to the T. gondii infection. In the mice deficient
      in MyD88 in DCs, the early IL-12 response by DCs was ablated, the IFN-gamma
      response by natural killer cells was delayed, and the recruited inflammatory
      monocytes were incapable of killing the T. gondii parasites. The T-cell response,
      although attenuated in these mice, was sufficient to eradicate the parasite
      during the chronic stage, provided that defects in DC activation were compensated
      by IL-12 treatment early after infection. These results demonstrate a central
      role of DCs in orchestrating the innate immune response to an intracellular
      pathogen and establish that defects in pathogen recognition by DCs can
      predetermine sensitivity to infection.

PMID- 21173241
TI  - Feasibility of reconstructed ancestral H5N1 influenza viruses for cross-clade
      protective vaccine development.
AB  - Since the reemergence of highly pathogenic H5N1 influenza viruses in humans in
      2003, these viruses have spread throughout avian species in Asia, Europe, and
      Africa. Their sustained circulation has resulted in the evolution of
      phylogenetically diverse lineages. Viruses from these lineages show considerable
      antigenic variation, which has confounded vaccine planning efforts. We
      reconstructed ancestral protein sequences at several nodes of the hemagglutinin
      (HA) and neuraminidase (NA) gene phylogenies that represent ancestors to diverse
      H5N1 virus clades. By using the same methods that have been used to generate
      currently licensed inactivated H5N1 vaccines, we were able to produce a panel of
      replication competent influenza viruses containing synthesized HA and NA genes
      representing the reconstructed ancestral proteins. We identified two of these
      viruses that showed promising in vitro cross-reactivity with clade 1, 2.1, 2.2,
      2.3.4, and 4 viruses. To confirm that vaccine antigens derived from these viruses
      were able to elicit functional antibodies following immunization, we created
      whole-virus vaccines and compared their protective efficacy versus that of
      antigens from positive control, naturally occurring, and broadly reactive H5N1
      viruses. The ancestral viruses' vaccines provided robust protection against
      morbidity and mortality in ferrets challenged with H5N1 strains from clades 1,
      2.1, and 2.2 in a manner similar to those based on the control strains. These
      findings provide proof of principle that viable, computationally derived vaccine
      seed viruses can be constructed within the context of currently licensed vaccine
      platforms. Such technologies should be explored to enhance the cross reactivity
      and availability of H5N1 influenza vaccines.

PMID- 21173243
TI  - Recruited inflammatory monocytes stimulate antiviral Th1 immunity in infected
      tissue.
AB  - Monocytes patrol various tissues for signs of infection and inflammation.
      Inflammatory monocytes enter peripheral tissues at sites of microbial infection
      and differentiate into dendritic cells and macrophages. Here, we examined the
      importance of monocytes in primary mucosal infection with herpes simplex virus 2
      (HSV-2), and demonstrate that monocyte-derived APCs are required to elicit IFN
      gamma secretion from effector Th1 cells to mediate antiviral protection. However,
      monocyte-derived APCs were dispensable for the generation of Th1 immunity and for
      the restimulation of memory Th1 cells during secondary viral challenge. These
      results demonstrate that distinct APC subsets are dedicated for CD4 T cell
      priming, elicitation, and memory recall responses to a given viral pathogen
      within the same mucosal tissue and reveal a specialized role for monocyte-derived
      APCs in the emergency response to infection.

PMID- 21173244
TI  - Artificial gene amplification reveals an abundance of promiscuous resistance
      determinants in Escherichia coli.
AB  - Duplicated genes provide an important raw material for adaptive evolution.
      However, the relationship between gene duplication and the emergence of new
      biochemical functions is complicated, and it has been difficult to quantify the
      likelihood of evolving novelty in any systematic manner. Here, we describe a
      comprehensive search for artificially amplified genes that are able to impart new
      phenotypes on Escherichia coli, provided their expression is up-regulated. We
      used a high-throughput, library-on-library strategy to screen for resistance to
      antibiotics and toxins. Cells containing a complete E. coli ORF library were
      exposed to 237 toxin-containing environments. From 86 of these environments, we
      identified a total of 115 cases where overexpressed ORFs imparted improved
      growth. Of the overexpressed ORFs that we tested, most conferred small but
      reproducible increases in minimum inhibitory concentration (<=16-fold) for their
      corresponding antibiotics. In many cases, proteins were acting promiscuously to
      impart resistance. In the absence of toxins, most strains bore no fitness cost
      associated with ORF overexpression. Our results show that even the genome of a
      nonpathogenic bacterium harbors a substantial reservoir of resistance genes,
      which can be readily accessed through overexpression mutations. During the growth
      of a population under selection, these mutations are most likely to be gene
      amplifications. Therefore, our work provides validation and biochemical insight
      into the innovation, amplification, and divergence model of gene evolution under
      continuous selection [Bergthorsson U, Andersson DI, Roth JR (2007) Proc Natl Acad
      Sci USA 104:17004-17009], and also illustrates the high frequency at which novel
      traits can evolve in bacterial populations.

PMID- 21173245
TI  - Support for agriculture during economic transformation: impacts on poverty and
      undernutrition.
AB  - This paper explores trends in poverty and nutrition during economic
      transformation and especially the impacts linked to government support for
      agriculture during the process. Analysis of multiyear data for 29 developing
      countries confirms that structural transformation raises total income and that
      poverty falls faster with strong support for agriculture. In turn, poverty
      reduction supports improved nutrition, especially in rural areas. However,
      transformation brings problems through health risks associated with rising
      obesity in rural as well as urban areas. Thus, the transition process must be
      managed better, through targeted support for smallholder agriculture and health
      interventions, if the negative consequences of obesity and chronic disease are to
      be mitigated.

PMID- 21173246
TI  - Chimpanzees as an animal model for human norovirus infection and vaccine
      development.
AB  - Noroviruses are global agents of acute gastroenteritis, but the development of
      control strategies has been hampered by the absence of a robust animal model.
      Studies in chimpanzees have played a key role in the characterization of several
      fastidious hepatitis viruses, and we investigated the feasibility of such studies
      for the noroviruses. Seronegative chimpanzees inoculated i.v. with the human
      norovirus strain Norwalk virus (NV) did not show clinical signs of
      gastroenteritis, but the onset and duration of virus shedding in stool and serum
      antibody responses were similar to that observed in humans. NV RNA was detected
      in intestinal and liver biopsies concurrent with the detection of viral shedding
      in stool, and NV antigen expression was observed in cells of the small intestinal
      lamina propria. Two infected chimpanzees rechallenged 4, 10, or 24 mo later with
      NV were resistant to reinfection, and the presence of NV-specific serum
      antibodies correlated with protection. We evaluated the immunogenicity and
      efficacy of virus-like particles (VLPs) derived from NV (genogroup I, GI) and
      MD145 (genogroup II, GII) noroviruses as vaccines. Chimpanzees vaccinated
      intramuscularly with GI VLPs were protected from NV infection when challenged 2
      and 18 mo after vaccination, whereas chimpanzees that received GII VLPs vaccine
      or a placebo were not. This study establishes the chimpanzee as a viable animal
      model for the study of norovirus replication and immunity, and shows that NV VLP
      vaccines could induce protective homologous immunity even after extended periods
      of time.

PMID- 21173247
TI  - Essential role for mast cell tryptase in acute experimental colitis.
AB  - Patients with inflammatory bowel disease (IBD) have increased numbers of human
      tryptase-beta (hTryptase-beta)-positive mast cells (MCs) in the gastrointestinal
      tract. The amino acid sequence of mouse mast cell protease (mMCP)-6 is most
      similar to that of hTryptase-beta. We therefore hypothesized that this mMCP, or
      the related tryptase mMCP-7, might have a prominent proinflammatory role in
      experimental colitis. The dextran sodium sulfate (DSS) and trinitrobenzene
      sulfonic acid (TNBS) colitis models were used to evaluate the differences between
      C57BL/6 (B6) mouse lines that differ in their expression of mMCP-6 and mMCP-7
      with regard to weight loss, colon histopathology, and endoscopy scores.
      Microarray analyses were performed, and confirmatory real-time PCR, ELISA, and/or
      immunohistochemical analyses were carried out on a number of differentially
      expressed cytokines, chemokines, and matrix metalloproteinases (MMPs). The mMCP-6
      null mice that had been exposed to DSS had significantly less weight loss as well
      as significantly lower pathology and endoscopy scores than similarly treated mMCP
      6-expressing mice. This difference in colitis severity was confirmed
      endoscopically in the TNBS-treated mice. Evaluation of the distal colon segments
      revealed that numerous proinflammatory cytokines, chemokines that preferentially
      attract neutrophils, and MMPs that participate in the remodeling of the ECM were
      all markedly increased in the colons of DSS-treated WT mice relative to untreated
      WT mice and DSS-treated mMCP-6-null mice. Collectively, our data show that mMCP-6
      (but not mMCP-7) is an essential MC-restricted mediator in chemically induced
      colitis and that this tryptase acts upstream of many of the factors implicated in
      IBD.

PMID- 21173248
TI  - Adaptive divergence between incipient species of Anopheles gambiae increases
      resistance to Plasmodium.
AB  - The African malaria mosquito Anopheles gambiae is diversifying into ecotypes
      known as M and S forms. This process is thought to be promoted by adaptation to
      different larval habitats, but its genetic underpinnings remain elusive. To
      identify candidate targets of divergent natural selection in M and S, we
      performed genomewide scanning in paired population samples from Mali, followed by
      resequencing and genotyping from five locations in West, Central, and East
      Africa. Genome scans revealed a significant peak of M-S divergence on chromosome
      3L, overlapping five known or suspected immune response genes. Resequencing
      implicated a selective target at or near the TEP1 gene, whose complement C3-like
      product has antiparasitic and antibacterial activity. Sequencing and allele
      specific genotyping showed that an allelic variant of TEP1 has been swept to
      fixation in M samples from Mali and Burkina Faso and is spreading into
      neighboring Ghana, but is absent from M sampled in Cameroon, and from all sampled
      S populations. Sequence comparison demonstrates that this allele is related to,
      but distinct from, TEP1 alleles of known resistance phenotype. Experimental
      parasite infections of advanced mosquito intercrosses demonstrated a strong
      association between this TEP1 variant and resistance to both rodent malaria and
      the native human malaria parasite Plasmodium falciparum. Although malaria
      parasites may not be direct agents of pathogen-mediated selection at TEP1 in
      nature--where larvae may be the more vulnerable life stage--the process of
      adaptive divergence between M and S has potential consequences for malaria
      transmission.

PMID- 21173249
TI  - Fibroblast-specific protein 1 identifies an inflammatory subpopulation of
      macrophages in the liver.
AB  - Cirrhosis is the end result of chronic liver disease. Hepatic stellate cells
      (HSC) are believed to be the major source of collagen-producing myofibroblasts in
      cirrhotic livers. Portal fibroblasts, bone marrow-derived cells, and epithelial
      to mesenchymal transition (EMT) might also contribute to the myofibroblast
      population in damaged livers. Fibroblast-specific protein 1 (FSP1, also called
      S100A4) is considered a marker of fibroblasts in different organs undergoing
      tissue remodeling and is used to identify fibroblasts derived from EMT in several
      organs including the liver. The aim of this study was to characterize FSP1
      positive cells in human and experimental liver disease. FSP1-positive cells were
      increased in human and mouse experimental liver injury including liver cancer.
      However, FSP1 was not expressed by HSC or type I collagen-producing fibroblasts.
      Likewise, FSP1-positive cells did not express classical myofibroblast markers,
      including alphaSMA and desmin, and were not myofibroblast precursors in injured
      livers as evaluated by genetic lineage tracing experiments. Surprisingly, FSP1
      positive cells expressed F4/80 and other markers of the myeloid-monocytic lineage
      as evaluated by double immunofluorescence staining, cell fate tracking, flow
      cytometry, and transcriptional profiling. Similar results were obtained for bone
      marrow-derived and peritoneal macrophages. FSP1-positive cells were characterized
      by increased expression of COX2, osteopontin, inflammatory cytokines, and
      chemokines but reduced expression of MMP3 and TIMP3 compared with Kupffer
      cells/macrophages. These findings suggest that FSP1 is a marker of a specific
      subset of inflammatory macrophages in liver injury, fibrosis, and cancer.

PMID- 21173250
TI  - Neural systems predicting long-term outcome in dyslexia.
AB  - Individuals with developmental dyslexia vary in their ability to improve reading
      skills, but the brain basis for improvement remains largely unknown. We performed
      a prospective, longitudinal study over 2.5 y in children with dyslexia (n = 25)
      or without dyslexia (n = 20) to discover whether initial behavioral or brain
      measures, including functional MRI (fMRI) and diffusion tensor imaging (DTI), can
      predict future long-term reading gains in dyslexia. No behavioral measure,
      including widely used and standardized reading and language tests, reliably
      predicted future reading gains in dyslexia. Greater right prefrontal activation
      during a reading task that demanded phonological awareness and right superior
      longitudinal fasciculus (including arcuate fasciculus) white-matter organization
      significantly predicted future reading gains in dyslexia. Multivariate pattern
      analysis (MVPA) of these two brain measures, using linear support vector machine
      (SVM) and cross-validation, predicted significantly above chance (72% accuracy)
      which particular child would or would not improve reading skills (behavioral
      measures were at chance). MVPA of whole-brain activation pattern during
      phonological processing predicted which children with dyslexia would improve
      reading skills 2.5 y later with >90% accuracy. These findings identify right
      prefrontal brain mechanisms that may be critical for reading improvement in
      dyslexia and that may differ from typical reading development. Brain measures
      that predict future behavioral outcomes (neuroprognosis) may be more accurate, in
      some cases, than available behavioral measures.

PMID- 21173251
TI  - Family level phylogenies reveal modes of macroevolution in RNA viruses.
AB  - Despite advances in understanding the patterns and processes of microevolution in
      RNA viruses, little is known about the determinants of viral diversification at
      the macroevolutionary scale. In particular, the processes by which viral lineages
      assigned as different "species" are generated remain largely uncharacterized. To
      address this issue, we use a robust phylogenetic approach to analyze patterns of
      lineage diversification in five representative families of RNA viruses. We ask
      whether the process of lineage diversification primarily occurs when viruses
      infect new host species, either through cross-species transmission or
      codivergence, and which are defined here as analogous to allopatric speciation in
      animals, or by acquiring new niches within the same host species, analogous to
      sympatric speciation. By mapping probable primary host species onto family level
      viral phylogenies, we reveal a strong clustering among viral lineages that infect
      groups of closely related host species. Although this is consistent with lineage
      diversification within individual hosts, we argue that this pattern more likely
      represents strong biases in our knowledge of viral biodiversity, because we also
      find that better-sampled human viruses rarely cluster together. Hence, although
      closely related viruses tend to infect related host species, it is unlikely that
      they often infect the same host species, such that evolutionary constraints
      hinder lineage diversification within individual host species. We conclude that
      the colonization of new but related host species may represent the principle mode
      of macroevolution in RNA viruses.

PMID- 21173252
TI  - Both liver-X receptor (LXR) isoforms control energy expenditure by regulating
      brown adipose tissue activity.
AB  - Brown adipocytes are multilocular lipid storage cells that play a crucial role in
      nonshivering thermogenesis. Uncoupling protein 1 (UCP1) is a unique feature of
      brown fat cells that allows heat generation on sympathetic nervous system
      stimulation. As conventional transcriptional factors that are activated in
      various signaling pathways, liver-X receptors (LXRs) play important roles in many
      physiological processes. The role of LXRs in the regulation of energy homeostasis
      remains unclear, however. Female WT, LXRalphabeta(-/-), LXRalpha(-/-), and
      LXRbeta(-/-) mice were fed with either a normal diet (ND) or a high-carbohydrate
      diet (HCD) supplemented with or without GW3965-LXR agonist. LXRalphabeta(-/-)
      mice exhibited higher energy expenditure (EE) as well as higher UCP1 expression
      in brown adipose tissue (BAT) compared with WT mice on the HCD. In addition, long
      term treatment of WT mice with GW3965 showed lower EE at thermoneutrality (30 
      degrees C) and lower Ucp1 expression level in BAT. Furthermore, H&E staining of
      the BAT of LXRalphabeta(-/-) mice exhibited decreased lipid droplet size compared
      with WT mice on the HCD associated with a more intense UCP1-positive reaction.
      Quantification of triglyceride (TG) content in BAT showed lower TG accumulation
      in LXRbeta(-/-) mice compared with WT mice. Surprisingly, GW3965 treatment
      increased TG content (twofold) in the BAT of WT and LXRalpha(-/-) mice but not in
      LXRbeta(-/-) mice. Furthermore, glucose transporter (GLUT4) in the BAT of
      LXRalpha(-/-) and LXRbeta(-/-) mice was sixfold and fourfold increased,
      respectively, compared with WT mice on the ND. These findings suggest that
      LXRalpha as well as LXRbeta could play a crucial role in the regulation of energy
      homeostasis in female mice and may be a potential target for the treatment of
      obesity and energy regulation.

PMID- 21173253
TI  - Resistance to discodermolide, a microtubule-stabilizing agent and senescence
      inducer, is 4E-BP1-dependent.
AB  - Discodermolide is a microtubule-stabilizing agent that induces accelerated cell
      senescence. A discodermolide-resistant cell line, AD32, was generated from the
      human lung cancer cell line A549. We hypothesize that the major resistance
      mechanism in these cells is escape from accelerated senescence. AD32 cells have
      decreased levels of 4E-BP1 mRNA and protein, relative to the parental
      discodermolide-sensitive A549 cells. Lentiviral-mediated re-expression of wild
      type 4E-BP1 in AD32 cells increased the proliferation rate and reverted
      resistance to discodermolide via restoration of discodermolide-induced
      accelerated senescence. Consistent with this, cell growth and response to
      discodermolide was confirmed in vivo using tumor xenograft models. Furthermore,
      reintroduction of a nonphosphorylatable mutant (Thr-37/46 Ala) of 4E-BP1 was able
      to partially restore sensitivity and enhance proliferation in AD32 cells,
      suggesting that these effects are independent of phosphorylation by mTORC1.
      Microarray profiling of AD32-resistant cells versus sensitive A549 cells, and
      subsequent unbiased gene ontology analysis, identified molecular pathways and
      functional groupings of differentially expressed mRNAs implicated in overcoming
      discodermolide-induced senescence. The most statistically significant classes of
      differentially expressed genes included p53 signaling, G2/M checkpoint
      regulation, and genes involved in the role of BRCA1 in the DNA damage response.
      Consistent with this, p53 protein expression was up-regulated and had increased
      nuclear localization in AD32 cells relative to parental A549 cells. Furthermore,
      the stability of p53 was enhanced in AD32 cells. Our studies propose a role for
      4E-BP1 as a regulator of discodermolide-induced accelerated senescence.

PMID- 21173254
TI  - Intrahost modeling of artemisinin resistance in Plasmodium falciparum.
AB  - Artemisinin-resistant Plasmodium falciparum malaria has emerged in western
      Cambodia. Resistance is characterized by prolonged in vivo parasite clearance
      times (PCTs) following artesunate treatment. The biological basis is unclear. The
      hypothesis that delayed parasite clearance results from a stage-specific
      reduction in artemisinin sensitivity of the circulating young asexual parasite
      ring stages was examined. A mathematical model was developed, describing the
      intrahost parasite stage-specific pharmacokinetic-pharmacodynamic relationships.
      Model parameters were estimated using detailed pharmacokinetic and parasite
      clearance data from 39 patients with uncomplicated falciparum malaria treated
      with artesunate from Pailin (western Cambodia) where artemisinin resistance was
      evident and 40 patients from Wang Pha (northwestern Thailand) where efficacy was
      preserved. The mathematical model reproduced the observed parasite clearance for
      each patient with an accurate goodness of fit (rmsd: 0.03-0.67 in log(10) scale).
      The parameter sets that provided the best fits with the observed in vivo data
      consist of a highly conserved concentration-effect relationship for the
      trophozoite and schizont parasite stages, but a variable relationship for the
      ring stages. The model-derived assessment suggests that the efficacy of
      artesunate on ring stage parasites is reduced significantly in Pailin. This
      result supports the hypothesis that artemisinin resistance mainly reflects
      reduced ring-stage susceptibility and predicts that doubling the frequency of
      dosing will accelerate clearance of artemisinin-resistant parasites.

PMID- 21173255
TI  - Global declines in oceanic nitrification rates as a consequence of ocean
      acidification.
AB  - Ocean acidification produced by dissolution of anthropogenic carbon dioxide
      (CO(2)) emissions in seawater has profound consequences for marine ecology and
      biogeochemistry. The oceans have absorbed one-third of CO(2) emissions over the
      past two centuries, altering ocean chemistry, reducing seawater pH, and affecting
      marine animals and phytoplankton in multiple ways. Microbially mediated ocean
      biogeochemical processes will be pivotal in determining how the earth system
      responds to global environmental change; however, how they may be altered by
      ocean acidification is largely unknown. We show here that microbial nitrification
      rates decreased in every instance when pH was experimentally reduced (by 0.05
      0.14) at multiple locations in the Atlantic and Pacific Oceans. Nitrification is
      a central process in the nitrogen cycle that produces both the greenhouse gas
      nitrous oxide and oxidized forms of nitrogen used by phytoplankton and other
      microorganisms in the sea; at the Bermuda Atlantic Time Series and Hawaii Ocean
      Time-series sites, experimental acidification decreased ammonia oxidation rates
      by 38% and 36%. Ammonia oxidation rates were also strongly and inversely
      correlated with pH along a gradient produced in the oligotrophic Sargasso Sea
      (r(2) = 0.87, P < 0.05). Across all experiments, rates declined by 8-38% in low
      pH treatments, and the greatest absolute decrease occurred where rates were
      highest off the California coast. Collectively our results suggest that ocean
      acidification could reduce nitrification rates by 3-44% within the next few
      decades, affecting oceanic nitrous oxide production, reducing supplies of
      oxidized nitrogen in the upper layers of the ocean, and fundamentally altering
      nitrogen cycling in the sea.

PMID- 21173257
TI  - Parathyroid hormone/parathyroid hormone-related protein receptor signaling is
      required for maintenance of the growth plate in postnatal life.
AB  - Parathyroid hormone (PTH)-related protein (PTHrP), regulated by Indian hedgehog
      and acting through the PTH/PTHrP receptor (PPR), is crucial for normal cartilage
      development. These observations suggest a possible role of PPR signaling in the
      postnatal growth plate; however, the role of PPR signaling in postnatal
      chondrocytes is unknown. In this study, we have generated tamoxifen-inducible and
      cartilage-specific PPR KO mice to evaluate the physiological role of PPR
      signaling in postnatal chondrocytes. We found that inactivation of the PPR in
      chondrocytes postnatally leads to accelerated differentiation of chondrocytes,
      followed by disappearance of the growth plate. We also observed an increase of
      TUNEL-positive cells and activities of caspase-3 and caspase-9 in the growth
      plate, along with a decrease in phosphorylation of Bad at Ser155 in postnatal PPR
      KO mice. Administration of a low-phosphate diet, which prevents apoptosis of
      chondrocytes, prevented the disappearance of the growth plate. Taken together,
      these observations suggest that the major consequences of PPR activation are
      similar in both the fetal and postnatal growth plates. Moreover, chondrocyte
      apoptosis through the activation of a mitochondrial pathway may be involved in
      the process of premature disappearance of the growth plate by postnatal
      inactivation of the PPR in chondrocytes.

PMID- 21173256
TI  - Evolving concepts of specificity in immune reactions.
AB  - Our goal is to provide a perspective on current understanding of the origins of
      specificity in immune reactions, a topic that has intrigued scientists for over a
      century. A fundamental property of adaptive immune responses is the ability to
      discriminate among an immense variety of substances by means of antibodies (Abs)
      and Ab-like receptors on T lymphocytes [T-cell receptors (TCRs)], each able to
      bind a particular chemical structure [the antigen (Ag)] and not, or only weakly,
      similar alternatives. Evidence has long existed, however, and has grown,
      especially recently, that while exhibiting remarkable specificity, many
      individual Abs and TCRs can also bind a variety of very different ligands. How
      can Ag recognition by these receptors exercise the great specificity for which
      they are renowned and yet react with a variety of different ligands (degeneracy)?
      We critically consider the mechanistic bases for this specificity/degeneracy
      enigma and also compare and contrast Ag recognition by Abs and TCRs.

PMID- 21173258
TI  - Nitrous oxide emission from denitrification in stream and river networks.
AB  - Nitrous oxide (N(2)O) is a potent greenhouse gas that contributes to climate
      change and stratospheric ozone destruction. Anthropogenic nitrogen (N) loading to
      river networks is a potentially important source of N(2)O via microbial
      denitrification that converts N to N(2)O and dinitrogen (N(2)). The fraction of
      denitrified N that escapes as N(2)O rather than N(2) (i.e., the N(2)O yield) is
      an important determinant of how much N(2)O is produced by river networks, but
      little is known about the N(2)O yield in flowing waters. Here, we present the
      results of whole-stream (15)N-tracer additions conducted in 72 headwater streams
      draining multiple land-use types across the United States. We found that stream
      denitrification produces N(2)O at rates that increase with stream water nitrate
      (NO(3)(-)) concentrations, but that <1% of denitrified N is converted to N(2)O.
      Unlike some previous studies, we found no relationship between the N(2)O yield
      and stream water NO(3)(-). We suggest that increased stream NO(3)(-) loading
      stimulates denitrification and concomitant N(2)O production, but does not
      increase the N(2)O yield. In our study, most streams were sources of N(2)O to the
      atmosphere and the highest emission rates were observed in streams draining urban
      basins. Using a global river network model, we estimate that microbial N
      transformations (e.g., denitrification and nitrification) convert at least 0.68
      Tg.y(-1) of anthropogenic N inputs to N(2)O in river networks, equivalent to 10%
      of the global anthropogenic N(2)O emission rate. This estimate of stream and
      river N(2)O emissions is three times greater than estimated by the
      Intergovernmental Panel on Climate Change.

PMID- 21173259
TI  - Mechanism of RNA stabilization and translational activation by a
      pentatricopeptide repeat protein.
AB  - Pentatricopeptide repeat (PPR) proteins comprise a large family of helical repeat
      proteins that bind RNA and modulate organellar RNA metabolism. The mechanisms
      underlying the functions attributed to PPR proteins are unknown. We describe in
      vitro studies of the maize protein PPR10 that clarify how PPR10 modulates the
      stability and translation of specific chloroplast mRNAs. We show that recombinant
      PPR10 bound to its native binding site in the chloroplast atpI-atpH intergenic
      region (i) blocks both 5'->3' and 3'-> 5 exoribonucleases in vitro; (ii) is
      sufficient to define the native processed atpH mRNA 5'-terminus in conjunction
      with a generic 5'->3' exoribonuclease; and (iii) remodels the structure of the
      atpH ribosome-binding site in a manner that can account for PPR10's ability to
      enhance atpH translation. In addition, we show that the minimal PPR10-binding
      site spans 17 nt. We propose that the site-specific barrier and RNA remodeling
      activities of PPR10 are a consequence of its unusually long, high-affinity
      interface with single-stranded RNA, that this interface provides a functional
      mimic to bacterial small RNAs, and that analogous activities underlie many of the
      biological functions that have been attributed to PPR proteins.

PMID- 21173260
TI  - Transient retinoic acid signaling confers anterior-posterior polarity to the
      inner ear.
AB  - Vertebrate hearing and balance are based in complex asymmetries of inner ear
      structure. Here, we identify retinoic acid (RA) as an extrinsic signal that acts
      directly on the ear rudiment to affect its compartmentalization along the
      anterior-posterior axis. A rostrocaudal wave of RA activity, generated by tissues
      surrounding the nascent ear, induces distinct responses from anterior and
      posterior halves of the inner ear rudiment. Prolonged response to RA by posterior
      otic tissue correlates with Tbx1 transcription and formation of mostly nonsensory
      inner ear structures. By contrast, anterior otic tissue displays only a brief
      response to RA and forms neuronal elements and most sensory structures of the
      inner ear.

PMID- 21173261
TI  - Vascular-mesenchymal cross-talk through Vegf and Pdgf drives organ patterning.
AB  - The initiation of de novo testis cord organization in the fetal gonad is poorly
      understood. Endothelial cell migration into XY gonads initiates testis
      morphogenesis. However, neither the signals that regulate vascularization of the
      gonad nor the mechanisms through which vessels affect tissue morphogenesis are
      known. Here, we show that Vegf signaling is required for gonad vascularization
      and cord morphogenesis. We establish that interstitial cells express Vegfa and
      respond, by proliferation, to endothelial migration. In the absence of
      vasculature, four-dimensional imaging of whole organs revealed that interstitial
      proliferation is reduced and prevents formation of wedge-like structures that
      partition the gonad into cord-forming domains. Antagonizing vessel maturation
      also reduced proliferation. However, proliferation of mesenchymal cells was
      rescued by the addition of PDGF-BB. These results suggest a pathway that
      integrates initiation of vascular development and testis cord morphogenesis, and
      lead to a model in which undifferentiated mesenchyme recruits blood vessels,
      proliferates in response, and performs a primary function in the morphogenesis
      and patterning of the developing organ.

PMID- 21173262
TI  - Lamin A variants that cause striated muscle disease are defective in anchoring
      transmembrane actin-associated nuclear lines for nuclear movement.
AB  - Mutations in LMNA, which encodes A-type lamins, result in disparate diseases,
      known collectively as laminopathies, that affect distinct tissues, including
      striated muscle and adipose tissue. Lamins provide structural support for the
      nucleus and sites of attachment for chromatin, and defects in these functions may
      contribute to disease pathogenesis. Recent studies suggest that A-type lamins may
      facilitate connections between the nucleus and the cytoskeleton mediated by
      nuclear envelope nesprin and SUN proteins. In mammalian cells, however,
      interfering with A-type lamins does not affect the localization of these
      proteins. Here, we used centrosome orientation in fibroblasts, which requires
      separate nuclear and centrosome positioning pathways, as a model system to
      understand how LMNA mutations affect nucleus-cytoskeletal connections. We find
      that LMNA mutations causing striated muscle diseases block actin-dependent
      nuclear movement, whereas most that affect adipose tissue inhibit microtubule
      dependent centrosome positioning. Genetic deletion or transient depletion of A
      type lamins also blocked nuclear movement, showing that mutations affecting
      muscle exhibit the null phenotype. Lack of A-type lamins, or expression of
      variants that cause striated muscle disease, did not affect assembly of nesprin
      2G and SUN2 into transmembrane actin-associated nuclear (TAN) lines that attach
      the nucleus to retrogradely moving actin cables. Nesprin-2G TAN lines were less
      stable, however, and slipped over the nucleus rather than moving with it,
      indicating that they were not anchored. Nesprin-2G TAN lines also slipped in SUN2
      depleted cells. Our results establish A-type lamins as anchors for nesprin-2G
      SUN2 TAN lines to allow productive movement and proper positioning of the nucleus
      by actin.

PMID- 21173263
TI  - Herbivorous ecomorphology and specialization patterns in theropod dinosaur
      evolution.
AB  - Interpreting key ecological parameters, such as diet, of extinct organisms
      without the benefit of direct observation or explicit fossil evidence poses a
      formidable challenge for paleobiological studies. To date, dietary
      categorizations of extinct taxa are largely generated by means of modern analogs;
      however, for many species the method is subject to considerable ambiguity. Here
      we present a refined approach for assessing trophic habits in fossil taxa and
      apply the method to coelurosaurian dinosaurs--a clade for which diet is
      particularly controversial. Our findings detect 21 morphological features that
      exhibit statistically significant correlations with extrinsic fossil evidence of
      coelurosaurian herbivory, such as stomach contents and a gastric mill. These
      traits represent quantitative, extrinsically founded proxies for identifying
      herbivorous ecomorphology in fossils and are robust despite uncertainty in
      phylogenetic relationships among major coelurosaurian subclades. The distribution
      of these features suggests that herbivory was widespread among coelurosaurians,
      with six major subclades displaying morphological evidence of the diet, and that
      contrary to previous thought, hypercarnivory was relatively rare and potentially
      secondarily derived. Given the potential for repeated, independent evolution of
      herbivory in Coelurosauria, we also test for repetitive patterns in the
      appearance of herbivorous traits within sublineages using rank concordance
      analysis. We find evidence for a common succession of increasing specialization
      to herbivory in the subclades Ornithomimosauria and Oviraptorosauria, perhaps
      underlain by intrinsic functional and/or developmental constraints, as well as
      evidence indicating that the early evolution of a beak in coelurosaurians
      correlates with an herbivorous diet.

PMID- 21173264
TI  - Posttranscriptional gene silencing in nuclei.
AB  - In plants, small interfering RNAs (siRNAs) with sequence homology to transcribed
      regions of genes can guide the sequence-specific degradation of corresponding
      mRNAs, leading to posttranscriptional gene silencing (PTGS). The current
      consensus is that siRNA-mediated PTGS occurs primarily in the cytoplasm where
      target mRNAs are localized and translated into proteins. However, expression of
      an inverted-repeat double-stranded RNA corresponding to the soybean FAD2-1A
      desaturase intron is sufficient to silence FAD2-1, implicating nuclear precursor
      mRNA (pre-mRNA) rather than cytosolic mRNA as the target of PTGS. Silencing FAD2
      1 using intronic or 3'-UTR sequences does not affect transcription rates of the
      target genes but results in the strong reduction of target transcript levels in
      the nucleus. Moreover, siRNAs corresponding to pre-mRNA-specific sequences
      accumulate in the nucleus. In Arabidopsis, we find that two enzymes involved in
      PTGS, Dicer-like 4 and RNA-dependent RNA polymerase 6, are localized in the
      nucleus. Collectively, these results demonstrate that siRNA-directed RNA
      degradation can take place in the nucleus, suggesting the need for a more complex
      view of the subcellular compartmentation of PTGS in plants.

PMID- 21173265
TI  - Genetic evidence for patrilocal mating behavior among Neandertal groups.
AB  - The remains of 12 Neandertal individuals have been found at the El Sidron site
      (Asturias, Spain), consisting of six adults, three adolescents, two juveniles,
      and one infant. Archaeological, paleontological, and geological evidence
      indicates that these individuals represent all or part of a contemporaneous
      social group of Neandertals, who died at around the same time and later were
      buried together as a result of a collapse of an underground karst. We sequenced
      phylogenetically informative positions of mtDNA hypervariable regions 1 and 2
      from each of the remains. Our results show that the 12 individuals stem from
      three different maternal lineages, accounting for seven, four, and one
      individual(s), respectively. Using a Y-chromosome assay to confirm the
      morphological determination of sex for each individual, we found that, although
      the three adult males carried the same mtDNA lineage, each of the three adult
      females carried different mtDNA lineages. These findings provide evidence to
      indicate that Neandertal groups not only were small and characterized by low
      genetic diversity but also were likely to have practiced patrilocal mating
      behavior.

PMID- 21173267
TI  - Pressure-induced superconductivity in topological parent compound Bi2Te3.
AB  - We report a successful observation of pressure-induced superconductivity in a
      topological compound Bi(2)Te(3) with T(c) of ~3 K between 3 to 6 GPa. The
      combined high-pressure structure investigations with synchrotron radiation
      indicated that the superconductivity occurred at the ambient phase without
      crystal structure phase transition. The Hall effects measurements indicated the
      hole-type carrier in the pressure-induced superconducting Bi(2)Te(3) single
      crystal. Consequently, the first-principles calculations based on the structural
      data obtained by the Rietveld refinement of X-ray diffraction patterns at high
      pressure showed that the electronic structure under pressure remained
      topologically nontrivial. The results suggested that topological
      superconductivity can be realized in Bi(2)Te(3) due to the proximity effect
      between superconducting bulk states and Dirac-type surface states. We also
      discuss the possibility that the bulk state could be a topological
      superconductor.

PMID- 21173266
TI  - How instructed knowledge modulates the neural systems of reward learning.
AB  - Recent research in neuroeconomics has demonstrated that the reinforcement
      learning model of reward learning captures the patterns of both behavioral
      performance and neural responses during a range of economic decision-making
      tasks. However, this powerful theoretical model has its limits. Trial-and-error
      is only one of the means by which individuals can learn the value associated with
      different decision options. Humans have also developed efficient, symbolic means
      of communication for learning without the necessity for committing multiple
      errors across trials. In the present study, we observed that instructed knowledge
      of cue-reward probabilities improves behavioral performance and diminishes
      reinforcement learning-related blood-oxygen level-dependent (BOLD) responses to
      feedback in the nucleus accumbens, ventromedial prefrontal cortex, and
      hippocampal complex. The decrease in BOLD responses in these brain regions to
      reward-feedback signals was functionally correlated with activation of the
      dorsolateral prefrontal cortex (DLPFC). These results suggest that when learning
      action values, participants use the DLPFC to dynamically adjust outcome responses
      in valuation regions depending on the usefulness of action-outcome information.

PMID- 21173268
TI  - Myogenic transcriptional activation of MyoD mediated by replication-independent
      histone deposition.
AB  - In mammals, the canonical histone H3 and the variant H3.3 are assembled into
      chromatin through replication-coupled and replication-independent (RI) histone
      deposition pathways, respectively, to play distinct roles in chromatin function.
      H3.3 is largely associated with transcriptionally active regions via the activity
      of RI histone chaperone, HIRA. However, the precise role of the RI pathway and
      HIRA in active transcription and the mechanisms by which H3.3 affects gene
      activity are not known. In this study, we show that HIRA is an essential factor
      for muscle development by establishing MyoD activation in myotubes. HIRA and
      Asf1a, but not CHD1 or Asf1b, mediate H3.3 incorporation in the promoter and the
      critical upstream regulatory regions of the MyoD gene. HIRA and H3.3 are required
      for epigenetic transition into the more permissive chromatin structure for
      polymerase II recruitment to the promoter, regardless of transcription-associated
      covalent modification of histones. Our results suggest distinct epigenetic
      management of the master regulator with RI pathway components for cellular
      differentiation.

PMID- 21173270
TI  - Nanodiamonds do not provide unique evidence for a Younger Dryas impact.
AB  - Microstructural, delta(13)C isotope and C/N ratio investigations were conducted
      on excavated material from the black Younger Dryas boundary in Lommel, Belgium,
      aiming for a characterisation of the carbon content and structures. Cubic diamond
      nanoparticles are found in large numbers. The larger ones with diameters around
      or above 10 nm often exhibit single or multiple twins. The smaller ones around 5
      nm in diameter are mostly defect-free. Also larger flake-like particles, around
      100 nm in lateral dimension, with a cubic diamond structure are observed as well
      as large carbon onion structures. The combination of these characteristics does
      not yield unique evidence for an exogenic impact related to the investigated
      layer.

PMID- 21173269
TI  - Quantifying the biophysical characteristics of Plasmodium-falciparum-parasitized
      red blood cells in microcirculation.
AB  - The pathogenicity of Plasmodium falciparum (Pf) malaria results from the
      stiffening of red blood cells (RBCs) and its ability to adhere to endothelial
      cells (cytoadherence). The dynamics of Pf-parasitized RBCs is studied by three
      dimensional mesoscopic simulations of flow in cylindrical capillaries in order to
      predict the flow resistance enhancement at different parasitemia levels. In
      addition, the adhesive dynamics of Pf-RBCs is explored for various parameters
      revealing several types of cell dynamics such as firm adhesion, very slow
      slipping along the wall, and intermittent flipping. The parasite inside the RBC
      is modeled explicitly in order to capture phenomena such as "hindered tumbling"
      motion of the RBC and the sudden transition from firm RBC cytoadherence to
      flipping on the endothelial surface. These predictions are in quantitative
      agreement with recent experimental observations, and thus the three-dimensional
      modeling method presented here provides new capabilities for guiding and
      interpreting future in vitro and in vivo studies of malaria.

PMID- 21173271
TI  - Experimental support for the evolution of symmetric protein architecture from a
      simple peptide motif.
AB  - The majority of protein architectures exhibit elements of structural symmetry,
      and "gene duplication and fusion" is the evolutionary mechanism generally
      hypothesized to be responsible for their emergence from simple peptide motifs.
      Despite the central importance of the gene duplication and fusion hypothesis,
      experimental support for a plausible evolutionary pathway for a specific protein
      architecture has yet to be effectively demonstrated. To address this question, a
      unique "top-down symmetric deconstruction" strategy was utilized to successfully
      identify a simple peptide motif capable of recapitulating, via gene duplication
      and fusion processes, a symmetric protein architecture (the threefold symmetric
      beta-trefoil fold). The folding properties of intermediary forms in this
      deconstruction agree precisely with a previously proposed "conserved
      architecture" model for symmetric protein evolution. Furthermore, a route through
      foldable sequence-space between the simple peptide motif and extant protein fold
      is demonstrated. These results provide compelling experimental support for a
      plausible evolutionary pathway of symmetric protein architecture via gene
      duplication and fusion processes.

PMID- 21173272
TI  - Cataract-associated mutant E107A of human gammaD-crystallin shows increased
      attraction to alpha-crystallin and enhanced light scattering.
AB  - Several point mutations in human gammaD-crystallin (HGD) are now known to be
      associated with cataract. So far, the in vitro studies of individual mutants of
      HGD alone have been sufficient in providing plausible molecular mechanisms for
      the associated cataract in vivo. Nearly all the mutant proteins in solution
      showed compromised solubility and enhanced light scattering due to altered
      homologous gamma-gamma crystallin interactions. In sharp contrast, here we
      present an intriguing case of a human nuclear cataract-associated mutant of HGD-
      namely Glu107 to Ala (E107A), which is nearly identical to the wild type in
      structure, stability, and solubility properties, with one exception: Its pI is
      higher by nearly one pH unit. This increase dramatically alters its interaction
      with alpha-crystallin. There is a striking difference in the liquid-liquid phase
      separation behavior of E107A-alpha-crystallin mixtures compared to HGD-alpha
      crystallin mixtures, and the light-scattering intensities are significantly
      higher for the former. The data show that the two coexisting phases in the E107A
      alpha mixtures differ much more in protein density than those that occur in HGD
      alpha mixtures, as the proportion of alpha-crystallin approaches that in the lens
      nucleus. Thus in HGD-alpha mixtures, the demixing of phases occurs primarily by
      protein type while in E107A-alpha mixtures it is increasingly governed by protein
      density. Analysis of these results suggests that the cataract due to the E107A
      mutation could result from the instability caused by the altered attractive
      interactions between dissimilar proteins--i.e., heterologous gamma-alpha
      crystallin interactions--primarily due to the change in surface electrostatic
      potential in the mutant protein.

PMID- 21173273
TI  - Derivation of Ca2+ signals from puff properties reveals that pathway function is
      robust against cell variability but sensitive for control.
AB  - Ca(2+) is a universal second messenger in eukaryotic cells transmitting
      information through sequences of concentration spikes. A prominent mechanism to
      generate these spikes involves Ca(2+) release from the endoplasmic reticulum
      Ca(2+) store via inositol 1,4,5-trisphosphate (IP(3))-sensitive channels. Puffs
      are elemental events of IP(3)-induced Ca(2+) release through single clusters of
      channels. Intracellular Ca(2+) dynamics are a stochastic system, but a complete
      stochastic theory has not been developed yet. We formulate the theory in terms of
      interpuff interval and puff duration distributions because, unlike the properties
      of individual channels, they can be measured in vivo. Our theory reproduces the
      typical spectrum of Ca(2+) signals like puffs, spiking, and bursting in
      analytically treatable test cases as well as in more realistic simulations. We
      find conditions for spiking and calculate interspike interval (ISI)
      distributions. Signal form, average ISI and ISI distributions depend sensitively
      on the details of cluster properties and their spatial arrangement. In contrast
      to that, the relation between the average and the standard deviation of ISIs does
      not depend on cluster properties and cluster arrangement and is robust with
      respect to cell variability. It is controlled by the global feedback processes in
      the Ca(2+) signaling pathway (e.g., via IP(3)-3-kinase or endoplasmic reticulum
      depletion). That relation is essential for pathway function because it ensures
      frequency encoding despite the randomness of ISIs and determines the maximal
      spike train information content. Hence, we find a division of tasks between
      global feedbacks and local cluster properties that guarantees robustness of
      function while maintaining sensitivity of control of the average ISI.

PMID- 21173276
TI  - Quantitative and empirical demonstration of the Matthew effect in a study of
      career longevity.
AB  - The Matthew effect refers to the adage written some two-thousand years ago in the
      Gospel of St. Matthew: "For to all those who have, more will be given." Even two
      millennia later, this idiom is used by sociologists to qualitatively describe the
      dynamics of individual progress and the interplay between status and reward.
      Quantitative studies of professional careers are traditionally limited by the
      difficulty in measuring progress and the lack of data on individual careers.
      However, in some professions, there are well-defined metrics that quantify career
      longevity, success, and prowess, which together contribute to the overall success
      rating for an individual employee. Here we demonstrate testable evidence of the
      age-old Matthew "rich get richer" effect, wherein the longevity and past success
      of an individual lead to a cumulative advantage in further developing his or her
      career. We develop an exactly solvable stochastic career progress model that
      quantitatively incorporates the Matthew effect and validate our model predictions
      for several competitive professions. We test our model on the careers of 400,000
      scientists using data from six high-impact journals and further confirm our
      findings by testing the model on the careers of more than 20,000 athletes in four
      sports leagues. Our model highlights the importance of early career development,
      showing that many careers are stunted by the relative disadvantage associated
      with inexperience.

PMID- 21173275
TI  - Dual role of the receptor Tom20 in specificity and efficiency of protein import
      into mitochondria.
AB  - Mitochondria import most of their resident proteins from the cytosol, and the
      import receptor Tom20 of the outer-membrane translocator TOM40 complex plays an
      essential role in specificity of mitochondrial protein import. Here we analyzed
      the effects of Tom20 binding on NMR spectra of a long mitochondrial presequence
      and found that it contains two distinct Tom20-binding elements. In vitro import
      and cross-linking experiments revealed that, although the N-terminal Tom20
      binding element is essential for targeting to mitochondria, the C-terminal
      element increases efficiency of protein import in the step prior to translocation
      across the inner membrane. Therefore Tom20 has a dual role in protein import into
      mitochondria: recognition of the targeting signal in the presequence and
      tethering the presequence to the TOM40 complex to increase import efficiency.

PMID- 21173278
TI  - Mechanism of inactivation of influenza viruses by immobilized hydrophobic
      polycations.
AB  - N,N-dodecyl,methyl-polyethylenimine coatings applied to solid surfaces have been
      shown by us to disinfect aqueous solutions of influenza viruses. Herein we
      elucidate the mechanism of this phenomenon. Infectivity-, protein-, RNA-, and
      scanning electron microscopy-based experiments reveal that, upon contact with the
      hydrophobic polycationic coating, influenza viruses (including pathogenic human
      and avian, both wild-type and drug-resistant, strains) irreversibly adhere to it,
      followed by structural damage and inactivation; subsequently, viral RNA is
      released into solution, while proteins remain adsorbed.

PMID- 21173277
TI  - Z-DNA-forming silencer in the first exon regulates human ADAM-12 gene expression.
AB  - Upregulation of ADAM-12, a novel member of the multifunctional ADAM family of
      proteins is linked to cancer, arthritis and cardiac hypertrophy. Basal expression
      of ADAM-12 is very low in adult tissues but rises markedly in response to certain
      physiological cues, such as during pregnancy in the placenta, during development
      in neonatal skeletal muscle and bone and in regenerating muscle. Studies on ADAM
      12 regulation have identified a highly conserved negative regulatory element
      (NRE) at the 5'-UTR of human ADAM-12 gene, which acts as a transcriptional
      repressor. The NRE contains a stretch of dinucleotide-repeat sequence that is
      able to adopt a Z-DNA conformation both in vitro and in vivo and interacts with
      hZalpha(ADAR1), a bona fide Z-DNA-binding protein. Substitution of the
      dinucleotide-repeat-element with a non-Z-DNA-forming sequence inhibited NRE
      function. We have detected a NRE DNA-binding protein activity in several tissues
      where ADAM-12 expression is low while no such activity was seen in the placenta
      where ADAM-12 expression is high. These observations suggest that interaction of
      these proteins with ADAM-12 NRE is critical for transcriptional repression of
      ADAM-12. We also show that the Z-DNA forming transcriptional repressor element,
      by interacting with these putative Z-DNA-binding proteins, is involved in the
      maintenance of constitutive low-level expression of human ADAM-12. Together these
      results provide a foundation for therapeutic down-regulation of ADAM-12 in
      cancer, arthritis and cardiac hypertrophy.

PMID- 21173280
TI  - Regarding Anderegg et al. and climate change credibility.

PMID- 21173279
TI  - Evolution in a family of chelatases facilitated by the introduction of active
      site asymmetry and protein oligomerization.
AB  - The class II chelatases associated with heme, siroheme, and cobalamin
      biosynthesis are structurally related enzymes that insert a specific metal ion
      (Fe(2+) or Co(2+)) into the center of a modified tetrapyrrole (protoporphyrin or
      sirohydrochlorin). The structures of two related class II enzymes, CbiX(S) from
      Archaeoglobus fulgidus and CbiK from Salmonella enterica, that are responsible
      for the insertion of cobalt along the cobalamin biosynthesis pathway are
      presented in complex with their metallated product. A further structure of a CbiK
      from Desulfovibrio vulgaris Hildenborough reveals how cobalt is bound at the
      active site. The crystal structures show that the binding of sirohydrochlorin is
      distinctly different to porphyrin binding in the protoporphyrin ferrochelatases
      and provide a molecular overview of the mechanism of chelation. The structures
      also give insights into the evolution of chelatase form and function. Finally,
      the structure of a periplasmic form of Desulfovibrio vulgaris Hildenborough CbiK
      reveals a novel tetrameric arrangement of its subunits that are stabilized by the
      presence of a heme b cofactor. Whereas retaining colbaltochelatase activity, this
      protein has acquired a central cavity with the potential to chaperone or
      transport metals across the periplasmic space, thereby evolving a new use for an
      ancient protein subunit.

PMID- 21173281
TI  - Long-term quality of life after surgical intensive care admission.
AB  - OBJECTIVES: To quantify the long-term (>6 years) health-related quality of life
      (HRQOL) of a large cohort of patients admitted to a surgical intensive care unit
      (ICU). In addition, we aimed to explore the influence of different surgical
      classifications on long-term health status and to make comparisons with general
      population norms. DESIGN: Prospective observational cohort study. SETTING: A
      Dutch teaching hospital. PATIENTS: All surviving surgical ICU patients admitted
      to the Dutch teaching hospital between 1995 and 2000. MAIN OUTCOME MEASURES:
      Patient-reported data on HRQOL were collected with the EuroQol-6D (EQ-6D) after a
      mean follow-up of 8 years (range, 6-11 years). Patient characteristics, surgical
      classification, length of ICU stay, and survival were prospectively registered.
      The EQ utility scores (measured with the EQ-5D US index tariff), EQ visual analog
      scale scores, and prevalences of domain-specific health problems were calculated.
      The effect of surgical classification on EQ utility scores and EQ visual analog
      scale scores was assessed by multivariable generalized linear regression
      analysis. Logistic regression was used to explore the influence of surgical
      classification on domain-specific health problems. Long-term HRQOL of surgical
      ICU patients was compared with an age- and sex-matched general Dutch population
      using t test analysis. RESULTS: Eight hundred thirty-four patients survived the
      ICU and were available for follow-up. In 575 patients (69%), the HRQOL was
      measured. For all surgical classifications combined, after 6 to 11 years, nearly
      half of all patients still had problems with mobility (52%), usual activity
      (52%), pain/discomfort (57%), and cognition (43%). Compared with the age- and sex
      matched general population, HRQOL was worse, with a difference of 0.11 on the EQ
      utility score (range, 0-1). Oncological surgery patients had the best (EQ utility
      score, 0.83) and vascular patients had the worst (EQ utility score, 0.72) HRQOL.
      Trauma (odds ratio between 2.47-3.47) and vascular surgery (odds ratio between
      2.27-5.37) patients showed significantly increased prevalences of problems in
      mobility, self-care, usual activities, and cognition. CONCLUSIONS: More than 6
      years after a surgical ICU admission, HRQOL of this patient population is largely
      reduced. Many patients still have a variety of health problems, including
      decreased cognitive functioning. Treatment advances should be made to reduce the
      current health deficit of surgical ICU survivors compared with the general
      population.

PMID- 21173282
TI  - Long-term impact of damage control laparotomy: a prospective study.
AB  - HYPOTHESIS: Damage control laparotomy (DCL) has beneficial effects on the long
      term morbidity and survival of trauma patients. DESIGN: Prospective study.
      SETTING: Level I trauma center. PATIENTS: Eighty-eight trauma patients who were
      admitted during a 3-year period (January 1, 2000, through December 31, 2003)
      underwent damage control laparotomy and were subsequently followed up (January 1,
      2001, through December 31, 2008). INTERVENTION: Damage control laparotomy. MAIN
      OUTCOME MEASURES: Major and long-term complications, lengths of stay, mortality,
      readmissions, subsequent surgical procedures, activities of daily living, and
      return to work. RESULTS: On admission, the mean age and Injury Severity Score
      were 33 years and 34, respectively. Of the 88 patients, 66 (75%) were male; 46
      patients had blunt injuries and 42 had penetrating injuries. Liver was the most
      common injury (63 patients), followed by bowel (34), spleen (33), major vessel
      (19), and pancreas (10). The mean admission pH and temperature were 7.19 and 34.4
      degrees C, respectively, with 21.5 U of packed red blood cells transfused. The
      mean (SD) number of initial abdominal operations was 4.6 (2.5) per patient, with
      an overall mortality of 28% (25 patients). Intensive care unit and hospital
      lengths of stay were 18 (15) and 32 (20) days, respectively. Of the 63 patients
      who survived, 58 underwent intra-abdominal closure with polyglactin mesh. During
      the study, 44 intra-abdominal infections and 18 enterocutaneous fistulas were
      diagnosed. All 63 survivors were readmitted at least once. There were a total of
      186 readmissions and 92 subsequent surgical procedures. Ventral hernia repair (66
      readmissions) was the most common reason for readmission, followed by infection
      (41) and fistula management (29). There was 0% mortality for patients who
      survived the preliminary hospitalization. Of the 63 surviving patients, 51 (81%)
      reported that they had gone back to work and resumed normal daily activities.
      CONCLUSION: Although damage control laparotomy is associated with a significant
      complication and readmission rate, its overall benefit is indisputable.

PMID- 21173284
TI  - Predictors of bleeding from stable pelvic fractures.
AB  - HYPOTHESIS: Stable pelvic fractures (SPFs) that do not need operative fixation
      are only infrequently associated with significant bleeding (SigBleed). Our
      hypothesis is that simple indicators, easily detectable at the bedside, can alert
      the clinician about the likelihood of bleeding and the need for closer monitoring
      or early intervention in patients with SPFs. DESIGN: Retrospective review of
      medical records. SETTING: Academic level 1 trauma center. PATIENTS: The medical
      records of patients with SPFs admitted to our academic level 1 trauma center from
      January 1, 2002, to June 30, 2007, were reviewed. Stable pelvic fractures were
      defined as fractures not requiring external or internal fixation. SigBleed was
      defined as the need for blood transfusion and/or intervention for bleeding
      control within the first 24 hours after admission. The patients were divided into
      group A, which included patients without SigBleed; group B, which included
      patients with SigBleed of a nonpelvic cause; and group C, which included patients
      with SigBleed caused by the SPF. The 3 groups were compared by univariate and
      multivariate analysis. MAIN OUTCOME MEASURE: Significant bleeding from SPFs.
      RESULTS: Of 391 patients with SPFs, 280 (72%) were in group A, 90 (23%) were in
      group B, and 21 (5%) were in group C. Compared with group A patients, those in
      group C were older and had a lower hematocrit and systolic blood pressure on
      admission. They also had longer hospital stays and a higher mortality. The
      following independent predictors of SigBleed from SPF were identified: hematocrit
      of 30% or lower (odds ratio [OR], 43.93; 95% confidence interval [CI], 9.78
      197.32; P < .001); presence of pelvic hematoma on computed tomographic scan (OR,
      39.37; 95% CI, 4.58-338.41; P < .001); and systolic blood pressure of 90 mm Hg or
      lower (OR, 18.352; 95% CI, 1.98-169.87; P = .01). When all independent predictors
      were present, 100% of the patients had SigBleed; when all were absent, no one had
      SigBleed. CONCLUSIONS: The incidence of SigBleed due to SPFs is low (5% in this
      study) and independently predicted by an admission hematocrit of 30% or lower,
      the presence of a pelvic hematoma on computed tomographic scan, and systolic
      blood pressure of 90 mm Hg or lower.

PMID- 21173285
TI  - Cost containment: think globally, act locally.

PMID- 21173283
TI  - Trends in diverticulitis management in the United States from 2002 to 2007.
AB  - OBJECTIVE: To demonstrate the recent trends of admission and surgical management
      for diverticulitis in the United States. DESIGN: Retrospective database analysis.
      SETTING: The National Inpatient Sample database. PATIENTS: Patients admitted to
      the hospital for diverticulitis from 2002 to 2007. MAIN OUTCOME MEASURES: Patient
      characteristics, surgical approach, and mortality were evaluated for elective or
      emergent admission. RESULTS: A total of 1,073,397 patients were admitted with
      diverticulitis (emergent: 78.3%, elective: 21.7%). The emergent admission rate
      increased by 9.5% over the study period. For emergent patients, 12.2% underwent
      urgent surgical resection and 87.8% were treated with nonoperative methods
      (percutaneous abscess drainage: 1.88% and medical treatment: 85.92%). There was
      only a 4.3% increase in urgent surgical resections, while elective surgical
      resections increased by 38.7.%. The overall rate of elective laparoscopic colon
      resection was 10.5%. Elective laparoscopic surgery nearly doubled from 6.9% in
      2002 to 13.5% in 2007 (P < .001). Primary anastomosis rates increased for
      elective resections over time (92.1% in 2002 to 94.5% in 2007; P < .001). For
      urgent open operation, use of colostomy decreased significantly from 61.2% in
      2002 to 54.0% in 2007 (P < .001). In-hospital mortality significantly decreased
      in both elective and urgent surgery (elective: 0.53% in 2002 to 0.44% in 2007; P
      = .001; urgent: 4.5% in 2002 to 2.5% in 2007; P < .001). CONCLUSION:
      Diverticulitis continues to be a source of significant morbidity in the United
      States. However, our data show a trend toward increased use of laparoscopic
      techniques for elective operations and primary anastomosis for urgent operations.

PMID- 21173286
TI  - Provider density and health system facility factors and their relationship to
      rates of pediatric perforated appendicitis in US counties.
AB  - OBJECTIVE: To examine whether density of providers or health care facility
      factors have a significant effect on the rates of perforated appendicitis in the
      pediatric population. DESIGN: A retrospective database analysis. Data were linked
      to the Area Resource File to determine if there was an association between
      perforated appendicitis and density of provider and facility factors. SETTING:
      The National Inpatient Sample database and the Kids' Inpatient Database from 1988
      to 2005. PATIENTS: All patients included had an age at admission of younger than
      18 years and were selected by International Classification of Diseases, Ninth
      Revision code as having perforated appendicitis (540.0 or 540.1) or acute
      appendicitis (540.9). Main Outcome Measure Odds ratio of perforated appendicitis
      to acute appendicitis by county-level density of provider and health care
      facility factors. RESULTS: The odds ratio of perforated appendicitis to acute
      appendicitis when stratified by quartiles of increasing density of providers and
      facility-level factors was statistically significant only for the highest-density
      quartile of pediatricians (odds ratio = 0.88; 95% confidence interval = 0.78
      0.99). CONCLUSIONS: Increasing geographic density of pediatricians was associated
      with a decreasing trend in the odds ratio of perforated appendicitis, with a
      statistically significant protective effect observed in the highest-density
      quartile of pediatricians. The density of all other provider and health care
      facility factors analyzed did not demonstrate a significant association with the
      rates of perforated appendicitis.

PMID- 21173287
TI  - Treatment for retained [corrected] common bile duct stones during laparoscopic
      cholecystectomy: the rendezvous technique.
AB  - OBJECTIVE: To determine the feasibility and efficacy of the laparoscopic
      intraoperative rendezvous technique for common bile duct stones (CBDS). DESIGN:
      Case series. SETTING: Verona University Hospital, Verona, Italy. PATIENTS: A
      total of 110 patients were enrolled in the study; 47 had biliary colic; 39, acute
      cholecystitis; 19, acute biliary pancreatitis; and 5, acute biliary pancreatitis
      with associated acute cholecystitis. INTERVENTIONS: In all patients, CBDS
      diagnosis was reached by intraoperative cholangiography. Intraoperative endoscopy
      with rendezvous performed during laparascopic cholecystectomy for confirmed CBDS;
      for such a procedure, a transcystic guide wire was positioned into the duodenum.
      Intraoperative endoscopy with rendezvous was performed for retrieved CBDS during
      a laparoscopic cholecystectomy. MAIN OUTCOME MEASURES: Laparoscopic rendezvous
      feasibility, morbidity, postprocedure pancreatitis, and mortality. RESULTS: The
      laparoscopic rendezvous proved to be feasible in 95.5% (105 of 110 patients). The
      rendezvous failed in 3 cases of successfully performed laparoscopic
      cholecystectomy, and a conversion of the laparoscopy was needed in 2 cases of
      successful rendezvous. Two major complications and 2 cases of bleeding were
      registered after sphincterotomy was successfully performed with rendezvous, and
      severe acute pancreatitis complicated a traditional sphincterotomy performed
      after a failed rendezvous. CONCLUSIONS: Rendezvous is a feasible option for
      treatment of CBDS; it allows one to perform only 1 stage of treatment, even in
      acute cases such as cholecystitis and pancreatitis. Positioning of the guide wire
      may allow reduced complications secondary to papilla cannulation but not those of
      the endoscopic sphincterotomy.

PMID- 21173288
TI  - A human factors curriculum for surgical clerkship students.
AB  - HYPOTHESIS: Early introduction of a full-day human factors training experience
      into the surgical clerkship curriculum will teach effective communication skills
      and strategies to gain professional satisfaction from a career in surgery.
      DESIGN: In pilot 1, which took place between July 1, 2007, and December 31, 2008,
      50 students received training and 50 did not; all received testing at the end of
      the rotation for comparison of control vs intervention group performance. In
      pilot 2, a total of 50 students were trained and received testing before and
      after rotation to examine individual change over time. SETTING: University of
      Massachusetts Medical School. PARTICIPANTS: A total of 148 third-year medical
      students in required 12-week surgical clerkship rotations. INTERVENTIONS: Full
      day training with lecture and small-group exercises, cotaught by surgeons and
      educators, with focus on empathetic communication, time management, and teamwork
      skills. MAIN OUTCOME MEASURES: Empathetic communication skill, teamwork, and
      patient safety attitudes and self-reported use of time management strategies.
      RESULTS: Empathy scores were not higher for trained vs untrained groups in pilot
      1 but improved from 2.32 to 3.45 on a 5-point scale (P < .001) in pilot 2.
      Students also were more likely to ask for the nurse's perspective and to seek
      agreement on an action plan after team communication training (pilot 1, f = 7.52,
      P = .007; pilot 2, t = 2.65, P = .01). Results were mixed for work-life balance,
      with some trained groups scoring significantly lower than untrained groups in
      pilot 1 and no significant improvement shown in pilot 2. CONCLUSIONS: The
      significant increase in student-patient communication scores suggests that a
      brief focused presentation followed by simulation of difficult patient encounters
      can be successful. A video demonstration can improve interdisciplinary teamwork.

PMID- 21173289
TI  - Racial/ethnic disparities in access to care and survival for patients with early
      stage hepatocellular carcinoma.
AB  - OBJECTIVE: To determine whether controlling for differences in the use of
      invasive therapy affects racial/ethnic differences in survival of early-stage
      hepatocellular carcinoma (HCC). DESIGN: A retrospective cohort study using
      Surveillance, Epidemiology, and End Results (SEER) HCC data. Invasive therapy was
      defined as tumor ablation, hepatectomy, or liver transplant. Race/ethnicity was
      defined as white, black, Asian, Hispanic, or other. Racial/ethnic differences in
      overall and treatment-adjusted survival were assessed using the Kaplan-Meier
      method and base- and treatment-stratified multivariable Cox proportional hazards
      models. PATIENTS: All patients diagnosed as having stage I or II HCC from January
      1, 1995, through December 31, 2006 (N = 13 244). SETTING: Data were obtained from
      the National Cancer Institute's SEER registry. MAIN OUTCOME MEASURES: Differences
      in survival by race/ethnicity accounting for the use of invasive therapy and
      treatment benefit. RESULTS: Overall, 32.8% of patients received invasive therapy.
      We found higher mortality rates in the base survival model for black (hazard
      ratio [HR], 1.24; 95% confidence interval [CI], 1.15-1.33) and Hispanic (1.08;
      1.01-1.15) patients and lower mortality rates in Asian patients (0.87; 0.82-0.93)
      compared with whites. After treatment stratification, compared with white
      patients, blacks had a 12% higher mortality rate (HR, 1.11; 95% CI, 1.03-1.20),
      Hispanics had a similar mortality rate (0.97; 0.91-1.04), and Asians had a 16%
      lower mortality rate (0.84; 0.79-0.89). CONCLUSIONS: For early-stage HCC,
      racial/ethnic disparities in survival between minority and white patients are
      notable. After accounting for differences in stage, use of invasive therapy, and
      treatment benefit, no racial/ethnic survival disparity is evident between
      Hispanics and whites, but blacks have persistently poor survival.

PMID- 21173290
TI  - Working with a fixed operating room team on consecutive similar cases and the
      effect on case duration and turnover time.
AB  - HYPOTHESIS: If variation in procedure times could be controlled or better
      predicted, the cost of surgeries could be reduced through improved scheduling of
      surgical resources. This study on the impact of similar consecutive cases on the
      turnover, surgical, and procedure times tests the perception that repeating the
      same manual tasks reduces the duration of these tasks. We hypothesize that when a
      fixed team works on similar consecutive cases the result will be shorter turnover
      and procedure duration as well as less variation as compared with the situation
      without a fixed team. DESIGN: Case-control study. SETTING: St Franciscus
      Hospital, a large general teaching hospital in Rotterdam, the Netherlands.
      PATIENTS: Two procedures, inguinal hernia repair and laparoscopic
      cholecystectomy, were selected and divided across a control group and a study
      group. Patients were randomly assigned to the study or control group. MAIN
      OUTCOME MEASURES: Preparation time, surgical time, procedure time, and turnover
      time. RESULTS: For inguinal hernia repair, we found a significantly lower
      preparation time and 10 minutes less procedure time in the study group, as
      compared with the control group. Variation in the study group was lower, as
      compared with the control group. For laparoscopic cholecystectomy, preparation
      time was significantly lower in the study group, as compared with the control
      group. For both procedures, there was a significant decrease in turnover time.
      CONCLUSIONS: Scheduling similar consecutive cases and performing with a fixed
      team results in lower turnover times and preparation times. The procedure time of
      the inguinal hernia repair decreased significantly and has practical scheduling
      implications. For more complex surgery, like laparoscopic cholecystectomy, there
      is no effect on procedure time.

PMID- 21173291
TI  - Analysis of compliance and outcomes in a trauma system with a 2-hour transfer
      rule.
AB  - HYPOTHESIS: Minimizing time to definitive care in an effort to optimize outcomes
      is the goal of trauma systems. Toward this end, some systems have imposed
      standards on time to interfacility transfer. This study evaluates compliance and
      outcome in a system with a 2-hour transfer rule. DESIGN: Retrospective review.
      SETTING: State trauma registry data from 1999 to 2003. PATIENTS: Trauma patients
      who underwent interfacility transfer and those who did not. MAIN OUTCOME
      MEASURES: Time to transfer; Injury Severity Score; mortality; and time to
      operating room at second facility. These variables were then stratified by time
      to transfer. RESULTS: During the study period, there were 22 447 interfacility
      transfers. Overall transfer rate was 10.4%. Of the transfers, 4502 (20%) occurred
      within 2 hours. Median transfer time was 2 hours 21 minutes. Injury Severity
      Score, mortality, and number of patients with operation performed on same day of
      transfer were all higher for the group transferred within 2 hours in comparison
      with patients transferred on the same day of injury at greater than 2 hours.
      CONCLUSIONS: While the majority of transfers occur at greater than the mandated 2
      hour interval, the most seriously injured patients are reaching definitive care
      within 2 hours. Markers of acuity for patients transferred at greater than 2
      hours parallel those of the general trauma patient population. These data suggest
      that, in this system, provider-determined transfer time that exceeds 2 hours has
      no adverse effect on patient outcome. It appears to accomplish recognition and
      rapid transport of the most seriously ill. This may obviate the need for onerous
      system mandates that are not feasible or have poor compliance.

PMID- 21173292
TI  - Intensive risk-adjusted follow-up with the CEA, TPA, CA19.9, and CA72.4 tumor
      marker panel and abdominal ultrasonography to diagnose operable colorectal cancer
      recurrences: effect on survival.
AB  - HYPOTHESIS: Intensive risk-adjusted follow-up leads to improved resectability of
      tumor recurrences and better overall survival among patients who have undergone
      surgery for colorectal cancer. DESIGN: Long-term observational single-center
      study. SETTING: University of Pisa, Pisa, Italy. PATIENTS: One hundred eight
      disease-free patients who had undergone surgery for colorectal cancer were
      submitted to long-term follow-up with the serum CEA, TPA, CA19.9, and CA72.4
      tumor marker (TM) panel and abdominal ultrasonography. MAIN OUTCOME MEASURES:
      Sensitivities and specificities of TMs, abdominal ultrasonography, and abdominal
      and chest computed tomography (CT); the median survival among patients operated
      on and those not operated on and the cumulative 5-year overall survival among the
      entire group. RESULTS: Twenty-two patients with asymptomatic colorectal cancer
      recurred 32 times. The CEA, TPA, CA19.9, CA72.4, and TM panel sensitivities were
      46.9%, 34.4%, 9.4%, 9.4%, and 81.0%, respectively, and the mean (SD) lead times
      before confirmation of recurrence were 4.3 (4.8), 4.1 (4.7), 8.3 (10.9), 5.0
      (7.0), and 5.3 (5.8) months, respectively. Abdominal and chest CT sensitivities
      were 100.0%. Among 86 patients without recurrence, specificities of the TM panel
      and all panel markers were 100.0%, while specificities of abdominal
      ultrasonography, abdominal CT, and skeletal CT were 99.9%, 99.0%, and 100.0%,
      respectively. The median survival after first recurrence was 16 months (range, 3
      48 months) for 8 patients with recurrence who did not undergo second-line
      surgery. Among 14 remaining patients who underwent metastasectomy, the median
      survival after first recurrence was 37 months (range, 12-187 months; P = .03).
      Among the entire group of 108 patients, the cumulative 5-year overall survival
      was 88.7%. CONCLUSIONS: Long-term intensive risk-adjusted monitoring using the
      CEA, TPA, CA19.9, and CA72.4 TM panel and abdominal ultrasonography allows early
      detection of most recurrences. Patients can then undergo radical metastasectomy,
      with potentially improved overall survival.

PMID- 21173293
TI  - Single-incision laparoscopic surgery for cholecystectomy: a retrospective
      comparison with 4-port laparoscopic cholecystectomy.
AB  - OBJECTIVES: To report our experience with single-incision laparoscopic surgery
      (SILS) for cholecystectomy and to perform a retrospective comparison with
      conventional 4-port laparoscopic cholecystectomy. DESIGN, SETTING, AND PATIENTS:
      Data were prospectively collected for all patients undergoing SILS for
      cholecystectomy at St Mary's Hospital, Imperial College NHS Trust, London,
      England (n = 41 patients between June 13, 2008, and June 30, 2009) and compared
      with data for those who had undergone conventional 4-port laparoscopic
      cholecystectomy in the preceding year (n = 58 patients between June 26, 2007, and
      May 30, 2008). This included patient demographic data and intraoperative and
      postoperative outcomes. INTERVENTIONS: Four-port laparoscopic cholecystectomy and
      SILS for cholecystectomy. MAIN OUTCOME MEASURES: Operative time, conversion to
      open operation, and length of hospital stay. RESULTS: Operative time was longer
      with SILS for cholecystectomy compared with conventional laparoscopic
      cholecystectomy (P < .001). A correlation was seen between reducing SILS
      operative time and increasing experience (Spearman rank correlation coefficient, 
      0.29). Three patients in the SILS for cholecystectomy group required the addition
      of extra laparoscopic ports. No patients in the SILS for cholecystectomy group
      required conversion to open surgery compared with 4 patients in the standard
      laparoscopic cholecystectomy group. Patients stayed an average of 0.76 days
      following SILS for cholecystectomy and 1.53 days following conventional
      laparoscopic cholecystectomy. One patient in each group had a postoperative
      biliary leak. CONCLUSIONS: Single-incision laparoscopic surgery for
      cholecystectomy may be equal to conventional laparoscopic cholecystectomy in
      terms of safety and efficacy. Further randomized studies are required to
      investigate any significant advantages of this new and attractive technique.

PMID- 21173295
TI  - Profile of inpatient operating room procedures in US hospitals in 2007.
AB  - OBJECTIVE: To provide an overview of inpatient operating room (OR) procedures in
      the United States. DESIGN, SETTING, AND PATIENTS: Healthcare Cost and Utilization
      Project 2007 Nationwide Inpatient Sample discharge data from a sample of US short
      term, acute-care, nonfederal hospitals. MAIN OUTCOME MEASURES: National volume of
      OR procedures overall and by type of procedure, resource use and costs, most
      frequent and expensive procedures, and trends. RESULTS: Fifteen million OR
      procedures were performed in 2007 (495 procedures/10 000 population). Only 26.4%
      of hospitalizations involved an OR procedure; however, OR-related stays were
      responsible for 46.8% of hospital costs ($161 billion). Patients aged 65 years
      and older were 2 to 3 times more likely to experience OR procedures (eg, 1327
      procedures/10 000 persons among those aged 65-84 years vs 626 procedures/10 000
      persons for those aged 45-64 years). Compared with non-OR inpatients, OR patients
      were less severely ill (20.5% had the highest severity of illness vs 24.6% for
      non-OR patients) and used more resources ($2900/day for OR patients vs $1400/day
      for non-OR patients). The 15 most expensive procedures accounted for half of all
      procedure-related hospitalization costs and one-fourth of total hospital costs.
      Volumes for 4 of the most expensive procedures increased between 1997 and 2007:
      20% for percutaneous transluminal coronary angioplasty, 46% for cesarean
      delivery, 46% for knee replacement, and 45% for spinal fusion. The volume of
      percutaneous transluminal coronary angioplasty declined 20% from 2006 to 2007,
      compared with a 56% increase in the prior decade. CONCLUSIONS: Procedures in the
      OR represent a large portion of hospital costs, and these costs are concentrated
      in few procedure types.

PMID- 21173294
TI  - Conservative vs restrictive individualized goal-directed fluid replacement
      strategy in major abdominal surgery: A prospective randomized trial.
AB  - OBJECTIVES: To compare the influence of 2 volumes of fluid, integrated with goal
      directed fluid therapy, on hypovolemia (a key trigger of tissue hypoperfusion)
      and central venous oxygen saturation (Scvo2) and to assess their relationships
      with postoperative morbidity. DESIGN, SETTING, AND PATIENTS: A prospective,
      randomized trial of 70 consecutive patients undergoing major abdominal surgery.
      INTERVENTIONS: Patients were randomly assigned to 6 mL/kg/h of crystalloid (a
      restrictive fluid strategy) or 12 mL/kg/h of crystalloid (a more conservative
      fluid strategy). In both groups, a fluid bolus was administered when respiratory
      variation in peak aortic flow velocity (DeltaPV) was greater than 13%. Data on
      hypovolemia (DeltaPV > 13%), Scvo2, and postoperative complications were recorded
      for all patients. MAIN OUTCOME MEASURES: Overall incidence of postoperative
      complications, especially anastomotic leak and sepsis. RESULTS: Overall incidence
      of complications, including postoperative anastomotic leak and sepsis, was higher
      in the restrictive group than in the conservative group (all P < .05). The number
      of patients with hypovolemia increased significantly in the restrictive group
      compared with the conservative group (P < .001). The perioperative mean Scvo2 (P
      = .02) and mean minimum Scvo2 (P = .04) were significantly lower in the
      restrictive group than in the conservative group. Multivariate analysis showed
      that both hypovolemia and mean minimum Scvo2 were independently associated with
      anastomotic leak and sepsis. CONCLUSIONS: Excessive fluid restriction increased
      the level of hypovolemia, leading to reduced Scvo2 and thereby increased
      incidence of postoperative complications. Excessive fluid restriction should be
      applied cautiously in surgical patients. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00852449.

PMID- 21173296
TI  - Image of the month--quiz case. Angiosarcoma.

PMID- 21173297
TI  - Image of the month--quiz case. Bladder Rhabdomyosarcoma.

PMID- 21173298
TI  - Glucose control in critically ill patients with severe sepsis.

PMID- 21173299
TI  - Physician attitudes toward industry: room for improvement.

PMID- 21173300
TI  - Prognostic usefulness of sentinel lymph node biopsy for patients who have
      clinically node negative, localized, primary invasive cutaneous melanoma: a
      Bayesian analysis using informative published reports.
AB  - OBJECTIVE: To assess the prognostic value of sentinel lymph node biopsy status
      for patients with localized, clinically node negative, primary invasive cutaneous
      melanoma. DESIGN: Predictive value of positive or negative sentinel lymph node
      biopsy (SLNB) results for melanoma-related death, using raw numbers from
      informative publications. SETTING AND PARTICIPANTS: Reports comprising 50
      patients with cutaneous melanoma who had undergone SLNB, based on PubMed search
      (January 1, 1993, through June 3, 2010). MAIN OUTCOME MEASURE: Melanoma-related
      death. RESULTS: For the 2 informative reports of patients with tumors of
      intermediate thickness (1-4 mm), risk of melanoma-related death ranged from 26.2%
      to 31.6% for node-positive cases and from 9.7% to 15.6% for node-negative cases.
      Based on 4 informative reports of patients with thin tumors (<= 1 mm), risk of
      melanoma-related death ranged from 0% to 0.6% for both node-positive and node
      negative cases. For the single informative report of patients with thick tumors
      (>= 4 mm), risk of melanoma-related death was 32.5% for node-positive cases and
      30.1% for node-negative cases. For 19 informative case series with any tumor
      thickness, risk of melanoma-related death ranged from 0% to 47.8% for node
      positive cases and from 0% to 13.3% for node-negative cases. CONCLUSION:
      Prognostic information provided by SLNB status may be variably useful for
      patients who have tumors of intermediate thickness (1-4 mm) and not very useful
      for patients who have thin (<= 1 mm) or thick (>= 4 mm) tumors.

PMID- 21173301
TI  - Prevalence of the metabolic syndrome in psoriasis: results from the National
      Health and Nutrition Examination Survey, 2003-2006.
AB  - OBJECTIVES: To estimate the prevalence of the metabolic syndrome among
      individuals with psoriasis and to examine the association between these 2
      conditions in the general US population. DESIGN: Cross-sectional health survey of
      a nationally representative random sample of the noninstitutionalized civilian US
      population. SETTING: The National Health and Nutrition Examination Survey, 2003
      2006. PARTICIPANTS: The study included 6549 participants aged 20 to 59 years.
      MAIN OUTCOME MEASURES: Prevalence of the metabolic syndrome defined by the
      revised National Cholesterol Education Program Adult Treatment Panel III
      definition and odds ratios for associations after adjustment for age, sex,
      race/ethnicity, smoking status, and C-reactive protein levels. RESULTS: The
      prevalence of the metabolic syndrome was 40% among psoriasis cases and 23% among
      controls. According to 2008 US census data, the projected number of patients with
      psoriasis aged 20 to 59 years with the metabolic syndrome was 2.7 million. The
      univariate and multivariate odds ratios for patients with psoriasis and the
      metabolic syndrome were 2.16 (95% confidence interval, 1.16 to 4.03) and 1.96
      (1.01 to 3.77), respectively. The most common feature of the metabolic syndrome
      among patients with psoriasis was abdominal obesity, followed by
      hypertriglyceridemia and low levels of high-density lipoprotein cholesterol.
      CONCLUSIONS: The prevalence of the metabolic syndrome is high among individuals
      with psoriasis. Given the serious complications associated with the metabolic
      syndrome, this frequent comorbidity should be recognized and taken into account
      in the long-term treatment of individuals with psoriasis.

PMID- 21173303
TI  - UV-A and UV-B penetration of normal human cadaveric fingernail plate.
AB  - OBJECTIVE: To assess the extent to which UV-A and UV-B radiation can penetrate
      the human fingernail plate. DESIGN: The Dermalite UV light machine (National
      Biological, Beachwood, Ohio) was used as the source of UV radiation. The amount
      of UV-A and UV-B penetrating the nail plate was measured using a radiometer and
      compared with a control. SETTING: Academic phototherapy clinic. PATIENTS: Ten
      cadaver fingernails were obtained from 1 cadaver from the National Disease
      Research Interchange. Because the objective was to determine transmission through
      normal fingernails, grossly diseased or deformed nails were not used. MAIN
      OUTCOME MEASURES: The percentage of UV light penetration through each fingernail
      was calculated by dividing the amount of radiation measured when the fingernail
      was in front of the light by the amount of radiation measured when there was
      nothing in front of the light (UV with nail divided by UV without nail). RESULTS:
      All 10 fingernails completely blocked the UV-B light, reading 0 mW/cm(2) on the
      radiometer. The mean penetration of UV-A light through the fingernails was 1.65%,
      ranging from 0.56% for the right fifth digit to 2.43% for the left second digit.
      CONCLUSIONS: The nail plate completely blocked UV-B light, and only a minimal
      amount of UV-A light penetrated the nails. If UV is required to directly
      penetrate the nail to treat nail bed psoriasis, then these data suggest that
      therapeutic efficacy may be compromised by the intervening nail plate. This
      minimal penetration of UV-A light may explain why therapies such as psoralen-UV-A
      (PUVA) have low efficacy for the treatment of nail psoriasis.

PMID- 21173302
TI  - Reduction of Fas/CD95 promoter methylation, upregulation of Fas protein, and
      enhancement of sensitivity to apoptosis in cutaneous T-cell lymphoma.
AB  - OBJECTIVE: To explore the relationships among (Fas) promoter methylation, Fas
      expression, and apoptotic sensitivity in cutaneous T-cell lymphoma (CTCL).
      DESIGN: Laboratory investigation. SETTING: Dermatology research unit of a
      university medical center. SAMPLES: Five CTCL lines and Sezary syndrome blood.
      INTERVENTIONS: Treatment of cells with 5-azacytidine (aza), methotrexate, and
      interferon alfa-2b. MAIN OUTCOME MEASURES: Fas promoter methylation, Fas
      expression, and sensitivity to Fas-mediated apoptosis. RESULTS: Fas promoter
      methylation correlates inversely with the level of Fas transcript, protein, and
      apoptotic sensitivity in CTCL. Increased DNA methylation also correlates with
      decreased NFkB (nuclear factor kappa-light chain enhancer of activated B cells)
      binding to the Fas promoter. All of these relationships were reversed by the DNA
      demethylating agent, 5-aza. We found that methotrexate also functions as a DNA
      demethylating agent by depleting methyl donors and, together with interferon alfa
      2b, upregulates Fas and enhances sensitivity to Fas-mediated apoptosis.
      CONCLUSIONS: These findings help explain the previously reported impressive
      responses of patients with advanced CTCL to combination therapy with methotrexate
      and interferon alfa. They also provide a new rationale for the treatment of CTCL
      with methotrexate and its use in combination with other agents.

PMID- 21173304
TI  - Adalimumab for treatment of moderate to severe chronic plaque psoriasis of the
      hands and feet: efficacy and safety results from REACH, a randomized, placebo
      controlled, double-blind trial.
AB  - OBJECTIVE: To determine the efficacy, safety, and sustainability of response to
      adalimumab therapy for moderate to severe chronic plaque psoriasis involving
      hands and/or feet. DESIGN: Sixteen-week, randomized, double-blind, placebo
      controlled evaluation of adalimumab therapy for moderate to severe chronic plaque
      psoriasis involving the hands and/or feet with a 12-week open-label extension
      (Randomized Controlled Evaluation of Adalimumab in Treatment of Chronic Plaque
      Psoriasis of the Hands and Feet [REACH]). SETTING: Multicenter outpatient study
      in the United States and Canada. PARTICIPANTS: Patients with chronic plaque
      psoriasis on the hands and/or feet with a Physician's Global Assessment of hands
      and/or feet (hfPGA) score of "moderate" or above. INTERVENTION: Patients were
      randomized 2:1 to adalimumab (80 mg at week 0, then 40 mg every other week
      starting at week 1) or to matching placebo. MAIN OUTCOME MEASURE: Percentage of
      patients achieving an hfPGA score of "clear" or "almost clear" at week 16.
      RESULTS: Seventy-two patients (adalimumab [n = 49];placebo [n = 23]) were
      evaluated. Baseline percentages of patients with moderate and severe hfPGA scores
      were 76% and 24%, respectively, for the adalimumab group and 74% and 26%,
      respectively, for the placebo group. At week 16, 31% and 4% of patients
      randomized to adalimumab and placebo, respectively, achieved an hfPGA score of
      clear or almost clear (P = .01). At week 28, 80% of the hfPGA clear or almost
      clear response was maintained from week 16 (25% for patients randomized to
      adalimumab). Adverse events in both groups were generally mild to moderate. In
      both periods combined, nasopharyngitis (27% and 13% for adalimumab- and placebo
      treated patients, respectively) was most frequently reported. CONCLUSION:
      Adalimumab is efficacious and well tolerated for treatment of chronic plaque
      psoriasis of hands and/or feet, with efficacy largely maintained to 28 weeks.
      Trial Registration clinicaltrials.gov Identifier: NCT00735787.

PMID- 21173305
TI  - Xanthoma disseminatum: effective therapy with 2-chlorodeoxyadenosine in a case
      series.
AB  - BACKGROUND: Xanthoma disseminatum is a rare nonfamilial disease characterized by
      lipid deposition in skin and internal organs due to histiocytic cell
      proliferation, classified as a benign non-Langerhans cell histiocytosis. This
      chronic disease has no known established treatment. We report 8 cases of xanthoma
      disseminatum with treatment outcomes in long-term follow-up and provide a review
      of the medical literature. OBSERVATIONS: We studied clinical manifestations;
      disease course; histopathologic and immunopathological findings; and responses to
      treatment in 8 consecutively seen patients with xanthoma disseminatum, including
      follow-up. The follow-up period ranged from 3 months to 8 years. Five patients
      received 2-chlorodeoxyadenosine. Therapy with 2-chlorodeoxyadenosine was
      effective at inducing remission and long-term control of cutaneous lesions of
      xanthoma disseminatum in 5 cases. Adverse effects were minimal, and treatment was
      well tolerated. No improvement was noted in untreated patients. CONCLUSION: Among
      8 cases of xanthoma disseminatum, a positive response to treatment with 2
      chlorodeoxyadenosine was seen in 5 cases.

PMID- 21173306
TI  - Invasion of eukaryotic cells by Borrelia burgdorferi requires beta(1) integrins
      and Src kinase activity.
AB  - Lyme disease, caused by the bacterium Borrelia burgdorferi, is the most
      widespread tick-borne infection in the northern hemisphere that results in a
      multistage disorder with concomitant pathology, including arthritis. During late
      stage experimental infection in mice, B. burgdorferi evades the adaptive immune
      response despite the presence of borrelia-specific bactericidal antibodies. In
      this study we asked whether B. burgdorferi could invade fibroblasts or
      endothelial cells as a mechanism to model the avoidance from humorally based
      clearance. A variation of the gentamicin protection assay, coupled with the
      detection of borrelial transcripts following gentamicin treatment, indicated that
      a portion of B. burgdorferi cells were protected in the short term from
      antibiotic killing due to their ability to invade cultured mammalian cells. Long
      term coculture of B. burgdorferi with primary human fibroblasts provided
      additional support for intracellular protection. Furthermore, decreased invasion
      of B. burgdorferi in murine fibroblasts that do not synthesize the beta(1)
      integrin subunit was observed, indicating that beta(1)-containing integrins are
      required for optimal borrelial invasion. However, beta(1)-dependent invasion did
      not require either the alpha(5)beta(1) integrin or the borrelial fibronectin
      binding protein BBK32. The internalization of B. burgdorferi was inhibited by
      cytochalasin D and PP2, suggesting that B. burgdorferi invasion required the
      reorganization of actin filaments and Src family kinases (SFK), respectively.
      Taken together, these results suggest that B. burgdorferi can invade and retain
      viability in nonphagocytic cells in a process that may, in part, help to explain
      the phenotype observed in untreated experimental infection.

PMID- 21173307
TI  - Model of polymicrobial peritonitis that induces the proinflammatory and
      immunosuppressive phases of sepsis.
AB  - Severe sepsis is associated with early release of inflammatory mediators that
      contribute to the morbidity and mortality observed during the first stages of
      this syndrome. Although sepsis is a deadly, acute disease, high mortality rates
      have been observed in patients displaying evidence of sepsis-induced immune
      deactivation. Although the contribution of experimental models to the knowledge
      of pathophysiological and therapeutic aspects of human sepsis is undeniable, most
      of the current studies using animal models have focused on the acute,
      proinflammatory phase. We developed a murine model that reproduces the early
      acute phases but also the long-term consequences of human sepsis. We induced
      polymicrobial acute peritonitis (AP) by establishing a surgical connection
      between the cecum and the peritoneum, allowing the exit of intestinal bacteria.
      Using this model, we observed an acute phase with high mortality, leukopenia,
      increased interleukin-6 levels, bacteremia, and neutrophil activation. A peak of
      leukocytosis on day 9 or 10 revealed the persistence of the infection within the
      lung and liver, with inflammatory hepatic damage being shown by histological
      examination. Long-term (20 days) derangements in both innate and adaptive immune
      responses were found, as demonstrated by impaired systemic tumor necrosis factor
      alpha production in response to an inflammatory stimulus; a decreased primary
      humoral immune response and T cell proliferation, associated with an increased
      number of myeloid suppressor cells (Gr-1(+) CD11b(+)) in the spleen; and a low
      clearance capacity. This model provides a good approach to attempt novel
      therapeutic interventions directed to augmenting host immunity during late
      sepsis.

PMID- 21173308
TI  - Enhancement of experimental cutaneous leishmaniasis by Leishmania molecules is
      dependent on interleukin-4, serine protease/esterase activity, and parasite and
      host genetic backgrounds.
AB  - Most inbred strains of mice, like the BALB/c strain, are susceptible to
      Leishmania amazonensis infections and resistant to Leishmania braziliensis
      infections. This parasite-related difference could result from the activity of an
      L. amazonensis-specific virulence factor. In agreement with this hypothesis, it
      is shown here that the intravenous injection of BALB/c mice with L. amazonensis
      amastigote extract (LaE) but not the L. braziliensis extract confers
      susceptibility to L. braziliensis infection. This effect was associated with high
      circulating levels of IgG1 anti-L. amazonensis antibodies and with an increase in
      interleukin-4 (IL-4) production and a decrease in gamma interferon production by
      draining lymph node cells. Moreover, the effect was absent in IL-4-knockout mice.
      The biological activity in the LaE was not mediated by amphiphilic molecules and
      was inhibited by pretreatment of the extract with irreversible serine protease
      inhibitors. These findings indicate that the LaE contains a virulence-related
      factor that (i) enhances the Leishmania infection by promoting Th2-type immune
      responses, (ii) is not one of the immunomodulatory Leishmania molecules described
      so far, and (iii) is either a serine protease or has an effect that depends on
      that protease activity. In addition to being Leishmania species specific, the
      infection-enhancing activity was also shown to depend on the host genetic makeup,
      as LaE injections did not affect the susceptibility of C57BL/6 mice to L.
      braziliensis infection. The identification of Leishmania molecules with infection
      enhancing activity could be important for the development of a vaccine, since the
      up- or downmodulation of the immune response against a virulence factor could
      well contribute to controlling the infection.

PMID- 21173309
TI  - Development of a secondary immune response to Mycobacterium tuberculosis is
      independent of Toll-like receptor 2.
AB  - Published work indicates that the contribution of Toll-like receptor 2 (TLR2) to
      host resistance during acute Mycobacterium tuberculosis infection is marginal.
      However, in these studies, TLR2 participation in the memory immune response to M.
      tuberculosis was not determined. The substantial in vitro evidence that M.
      tuberculosis strongly triggers TLR2 on dendritic cells and macrophages to bring
      about either activation or inhibition of antigen-presenting cell (APC) functions,
      along with accumulating evidence that memory T cell development can be calibrated
      by TLR signals, led us to question the role of TLR2 in host resistance to
      secondary challenge with M. tuberculosis. To address this question, a memory
      immunity model was employed, and the response of TLR2-deficient (TLR2 knockout
      [TLR2KO]) mice following a secondary exposure to M. tuberculosis was compared to
      that of wild-type (WT) mice based on assessment of the bacterial burden, recall
      response, phenotype of recruited T cells, and granulomatous response. We found
      that upon rechallenge with M. tuberculosis, both WT and TLR2KO immune mice
      displayed similarly enhanced resistance to infection in comparison to their naive
      counterparts. The frequencies of M. tuberculosis-specific gamma interferon (IFN
      gamma)-producing T cells, the phenotypes of recruited T cells, and the
      granulomatous responses were also similar between WT and TLR2KO immune mice.
      Together, the findings from this study indicate that TLR2 signaling does not
      influence memory immunity to M. tuberculosis.

PMID- 21173310
TI  - Leptospira santorosai Serovar Shermani detergent extract induces an increase in
      fibronectin production through a Toll-like receptor 2-mediated pathway.
AB  - Leptospirosis can activate inflammatory responses through Toll-like receptors
      (TLRs) and may cause renal tubulointerstitial fibrosis characterized by the
      accumulation of extracellular matrix (ECM). We have previously demonstrated that
      Leptospira santorosai serovar Shermani detergent extract stimulates ECM
      accumulation in vitro. The aim of this study was to examine the mechanistic basis
      of these previous observations and, in particular, to examine the potential
      involvement of TLRs. The addition of serovar Shermani detergent extract led to an
      increase in fibronectin gene expression and production. Inhibition of TLR2 but
      not TLR4 expression abrogated serovar Shermani detergent extract-mediated
      increases in fibronectin production. This response was also blocked by the
      knockdown of the gene expression of the TLR2 downstream transducers myeloid
      differentiation factor 88 (MyD88) and tumor necrosis factor receptor-associated
      factor 6 (TRAF6). Serovar Shermani detergent extract also activated nuclear
      factor-kappaB, and its inhibition by curcumin-attenuated serovar Shermani
      detergent extract induced increases in fibronectin production. These effects were
      also mimicked by the specific TLR2 agonist, Pam(3)CsK(4), a response that was
      also abrogated by the knockdown of MyD88 and TRAF6. Similarly, the administration
      of live leptospires to cells also induced fibronectin production that was blocked
      by inhibition of TLR2 and MyD88 expression. In conclusion, serovar Shermani
      detergent extract can induce fibronectin production through the TLR2-associated
      cascade, providing evidence of an association between TLRs and leptospirosis
      mediated ECM deposition.

PMID- 21173311
TI  - ygs is a novel gene that influences biofilm formation and the general stress
      response of Staphylococcus epidermidis.
AB  - Infections caused by the nosocomial pathogen Staphylococcus epidermidis
      frequently develop on implanted medical devices and involve biofilm formation.
      Biofilms are surface-attached microbial communities that show increased
      resistance to drug treatment and mechanisms of innate host defense. In this
      study, a mutant library of the clinical isolate S. epidermidis 1457 was
      constructed using mariner-based transposon mutagenesis. About a thousand mutants
      were screened, and 12 mutants were identified as significantly defective in
      biofilm formation. We focused on a mutant in which the transposon had inserted in
      a gene with unknown function, SERP0541, which is annotated as a gene encoding a
      GSP13-like general stress response protein. The gene was named ygs (encoding an
      unknown general stress protein). Various stresses, including heat, pH, high
      osmolarity, and ethanol affected the survival of the ygs mutant to a
      significantly higher degree than the wild-type strain and led to increased
      expression of ygs. Furthermore, synthesis of polysaccharide intercellular adhesin
      (PIA) and transcription of the PIA biosynthetic operon were significantly
      decreased in the ygs mutant. These results are in accordance with the putative
      involvement of ygs in stress-response gene regulation and indicate that ygs
      influences biofilm development by controlling PIA-dependent biofilm accumulation.
      Moreover, ygs had a significant impact on the formation of biofilms and
      metastatic disease in two catheter-related rat infection models. Our study shows
      that the ygs gene controls S. epidermidis biofilm accumulation and stress
      resistance, representing a key regulator of both structural and physiological
      biofilm characteristics with a significant impact on biofilm-associated
      infection.

PMID- 21173312
TI  - BB0844, an RpoS-regulated protein, is dispensable for Borrelia burgdorferi
      infectivity and maintenance in the mouse-tick infectious cycle.
AB  - The genome of Borrelia burgdorferi, the causative agent of Lyme disease, is
      comprised of a large linear chromosome and numerous smaller linear and circular
      plasmids. B. burgdorferi exhibits substantial genomic variation, and previous
      studies revealed genotype-specific variation at the right chromosomal telomere. A
      correlation has also been established between genotype and invasiveness. The
      correlation between chromosome length and genotype and between genotype and
      invasiveness suggested that a gene(s) at the right chromosome telomere may be
      required for virulence. Of particular interest was bb0844, an RpoS-regulated gene
      at the right telomere, the expression of which is induced when the spirochete
      undergoes adaptation to the mammalian host. The structure of the right
      chromosomal telomere was examined in 53 B. burgdorferi clinical isolates of
      various genotypes. Four distinct patterns were observed for bb0844: (i)
      chromosomal localization, (ii) plasmid localization, (iii) presence on both
      chromosome and plasmid, and (iv) complete absence. These patterns correlated with
      the B. burgdorferi genotype. On the basis of available sequence data, we propose
      a mechanism for the genomic rearrangements that accounts for the variability in
      bb0844 genomic localization. To further explore the role of BB0844 in the
      spirochete life cycle, a bb0844 deletion mutant was constructed by allelic
      exchange, and the viability of wild-type and bb0844 deletion mutants was examined
      in an experimental mouse-tick infection model. The bb0844 mutant was fully
      infectious in C3H/HeJ mice by either needle inoculation or tick transmission with
      B. burgdorferi-infected Ixodes scapularis larvae. Naive larval ticks acquired
      both wild-type and mutant spirochetes with equal efficiency from B. burgdorferi
      infected mice. The results demonstrate that BB0844 is not required for spirochete
      viability, pathogenicity, or maintenance in the tick vector or the mammalian
      host. At present, a defined role for BB0844 in B. burgdorferi cannot be
      ascertained.

PMID- 21173313
TI  - Use of a Dictyostelium model for isolation of genetic loci associated with
      phagocytosis and virulence in Klebsiella pneumoniae.
AB  - Phagocytosis resistance is an important virulence factor in Klebsiella
      pneumoniae. Dictyostelium has been used to study the interaction between
      phagocytes and bacteria because of its similarity to mammalian macrophages. In
      this study, we used a Dictyostelium model to investigate genes for resistance to
      phagocytosis in NTUH-K2044, a strain of K. pneumoniae causing pyogenic liver
      abscess that is highly resistant to phagocytosis. A total of 2,500 transposon
      mutants were screened by plaque assay, and 29 of them permitted phagocytosis by
      Dictyostelium. In the 29 mutants, six loci were identified; three were capsular
      synthesis genes. Of the other three, one was related to carnitine metabolism, one
      encoded a subunit of protease (clpX), and one encoded a lipopolysaccharide O
      antigen transporter (wzm). Deletion and complementation of these genes showed
      that only DeltaclpX and Deltawzm mutants became susceptible to Dictyostelium
      phagocytosis, and their complementation restored the phagocytosis resistance
      phenotype. These two mutants were also susceptible to phagocytosis by human
      neutrophils and revealed attenuated virulence in a mouse model, implying that
      they play important roles in the pathogenesis of K. pneumoniae. Furthermore, we
      demonstrated that clpP, which exists in an operon with clpX, was also involved in
      resistance to phagocytosis. The transcriptional profile of DeltaclpX was examined
      by microarray analysis and revealed a 3-fold lower level of expression of
      capsular synthesis genes. Therefore, we have identified genes involved in
      resistance to phagocytosis in K. pneumoniae using Dictyostelium, and this model
      is useful to explore genes associated with resistance to phagocytosis in heavily
      encapsulated bacteria.

PMID- 21173315
TI  - An in vivo high-throughput screening approach targeting the type IV secretion
      system component VirB8 identified inhibitors of Brucella abortus 2308
      proliferation.
AB  - As bacterial pathogens develop resistance against most currently used
      antibiotics, novel alternatives for treatment of microbial infectious diseases
      are urgently needed. Targeting bacterial virulence functions in order to disarm
      pathogens represents a promising alternative to classical antibiotic therapy.
      Type IV secretion systems, which are multiprotein complexes in the cell envelope
      that translocate effectors into host cells, are critical bacterial virulence
      factors in many pathogens and excellent targets for such "antivirulence" drugs.
      The VirB8 protein from the mammalian pathogen Brucella was chosen as a specific
      target, since it is an essential type IV secretion system component, it
      participates in multiple protein-protein interactions, and it is essential for
      the assembly of this translocation machinery. The bacterial two-hybrid system was
      adapted to assay VirB8 interactions, and a high-throughput screen identified
      specific small-molecule inhibitors. VirB8 interaction inhibitors also reduced the
      levels of VirB8 and of other VirB proteins, and many of them inhibited virB gene
      transcription in Brucella abortus 2308, suggesting that targeting of the
      secretion system has complex regulatory effects in vivo. One compound strongly
      inhibited the intracellular proliferation of B. abortus 2308 in a J774 macrophage
      infection model. The results presented here show that in vivo screens with the
      bacterial two-hybrid assay are suited to the identification of inhibitors of
      Brucella type IV secretion system function.

PMID- 21173317
TI  - Severe refractory hidradenitis suppurativa in an HIV-positive patient
      successfully treated with infliximab.

PMID- 21173318
TI  - Pulmonary arterial hypertension in patients with slow-flow vascular
      malformations.
AB  - OBJECTIVE: To determine the prevalence of pulmonary arterial hypertension in
      asymptomatic patients with 2 types of extensive slow-flow vascular malformations:
      extensive venous malformations or Klippel-Trenaunay syndrome (KTS). DESIGN: Case
      control. SETTING: Multidisciplinary center for vascular anomalies. PATIENTS: A
      consecutive sample of 32 patients with slow-flow vascular malformations of at
      least 15% of the body surface was identified retrospectively and matched by age
      and sex with 32 healthy controls. INTERVENTIONS: Standard 2-dimensional
      transthoracic Doppler echocardiography. Venous samples were obtained the same day
      that echocardiography was performed. MAIN OUTCOME MEASURES: Pulmonary artery
      systolic pressure (PASP) was determined. Levels of D-dimer, fibrinogen, and von
      Willebrand factor (vWF) in plasma were measured. RESULTS: Patients had a mean
      (SD) PASP that was significantly higher than that of healthy controls (42.16
      [8.49] mm Hg in patients vs 27.69 [6.54] mm Hg in healthy controls; P < .001). No
      significant differences in PASP were found between patients with KTS and patients
      with venous malformations (P = .80). We observed significant differences in the
      mean (SD) levels of vWF between patients and healthy controls (124.41% [52.28%]
      in patients vs 92.69% [28.92%] in controls; P = .01) and also in levels of D
      dimer (1032.99 [1367.0] ng/mL in patients vs 102.97 [29.39] ng/mL in healthy
      controls; P < .001). There was a moderate positive correlation between levels of
      vWF and levels of PASP (r = 0.42; P = .001) and a high positive correlation
      between D-dimer and PASP (r = 0.52; P < .001) CONCLUSIONS: The presence of
      pulmonary arterial hypertension in patients with extensive slow-flow vascular
      malformations is not an isolated feature but is relatively frequent. Levels of D
      dimer correlate with PASP in these patients.

PMID- 21173314
TI  - Inactivation of bb0184, which encodes carbon storage regulator A, represses the
      infectivity of Borrelia burgdorferi.
AB  - The genome of Borrelia burgdorferi, the Lyme disease spirochete, encodes a
      homolog (the bb0184 gene product) of the carbon storage regulator A protein
      (CsrA(Bb)); recent studies reported that CsrA(Bb) is involved in the regulation
      of several infectivity factors of B. burgdorferi. However, the mechanism involved
      remains unknown. In this report, a csrA(Bb) mutant was constructed and
      complemented in an infectious B31A3 strain. Subsequent animal studies showed that
      the mutant failed to establish an infection in mice, highlighting that CsrA(Bb)
      is required for the infectivity of B. burgdorferi. Western blot analyses revealed
      that the virulence-associated factors OspC, DbpB, and DbpA were attenuated in the
      csrA(Bb) mutant. The Rrp2-RpoN-RpoS pathway (sigma(54)-sigma(S) sigma factor
      cascade) is a central regulon that governs the expression of ospC, dbpB, and
      dbpA. Further analyses found that the level of RpoS was significantly decreased
      in the mutant, while the level of Rrp2 remained unchanged. A recent study
      reported that the overexpression of BB0589, a phosphate acetyl-transferase (Pta)
      that converts acetyl-phosphate to acetyl-coenzyme A (CoA), led to the inhibition
      of RpoS and OspC expression, suggesting that acetyl-phosphate is an activator of
      Rrp2. Along with this report, we found that CsrA(Bb) binds to the leader sequence
      of the bb0589 transcript and that the intracellular level of acetyl-CoA in the
      csrA(Bb) mutant was significantly increased compared to that of the wild type,
      suggesting that more acetyl-phosphate was being converted to acetyl-CoA in the
      mutant. Collectively, these results suggest that CsrA(Bb) may influence the
      infectivity of B. burgdorferi via regulation of acetate metabolism and subsequent
      activation of the Rrp2-RpoN-RpoS pathway.

PMID- 21173319
TI  - Prevalence and characteristics of indoor tanning use among men and women in the
      United States.
AB  - Objectives  To describe the prevalence and characteristics related to indoor
      tanning use among adults in the United States in the past year. DESIGN: Cross
      sectional study. SETTING: Health Information National Trends Study, 2005.
      PARTICIPANTS: The study included 2869 participants who were white and aged 18 to
      64 years; a random subset of 821 participants were also asked questions about
      skin cancer prevention knowledge and attitudes. MAIN OUTCOME MEASURES: The study
      assessed the prevalence of self-reported use of indoor tanning in the past 12
      months and its associations with demographic and lifestyle factors, knowledge,
      and attitudes. RESULTS: Overall, 18.1% of women and 6.3% of men reported tanning
      indoors in the past 12 months. Women who were older, were less educated, had
      lower income, and used sunscreen regularly were less likely to report the
      behavior, while women residing in the Midwest and the South and who used spray
      tanning products were more likely to report the behavior. Men who were less
      likely to report the behavior were older and obese but more likely to report the
      behavior if they lived in metropolitan areas and used spray tanning products. In
      an open-response format, only 13.3% of women and 4.2% of men suggested that
      avoidance of tanning bed use could reduce their risks of skin cancer. Greater
      skin cancer knowledge and higher perceived risk of skin cancer were inversely
      associated with the behavior in women. CONCLUSIONS: Prevalence and some
      characteristics associated with indoor tanning use, such as sunscreen use,
      differed between women and men in the United States. Most adults did not
      volunteer avoidance of tanning bed use to prevent skin cancer. Clinician-patient
      communication on risks of indoor tanning may be helpful to reduce indoor tanning
      use.

PMID- 21173320
TI  - Counseling patients to avoid indoor tanning.

PMID- 21173321
TI  - Failure to counsel patients with psoriasis to decrease alcohol consumption (and
      smoking).

PMID- 21173322
TI  - Failure to recognize and manage patients with DRESS.

PMID- 21173323
TI  - Becker nevus with an underlying desmoid tumor: a case report and review including
      Mayo Clinic's experience.
AB  - BACKGROUND: Becker nevus is a nevoid melanosis, referred to as Becker nevus
      syndrome when it is associated with other anomalies. Our objectives were to
      report the occurrence of a Becker nevus with an underlying desmoid soft-tissue
      tumor; to review Mayo Clinic's experience with Becker nevi, concentrating on
      Becker nevi associated with bone, vascular, neural, and other soft-tissue
      abnormalities; to inform physicians of the Becker nevus syndrome; and finally to
      alert clinicians to evaluate a Becker nevus with its associations in mind.
      OBSERVATIONS: A 46-year-old woman had a Becker nevus with an underlying desmoid
      type fibromatosis (desmoid tumor) presenting clinically as a "painful dimple"
      within the nevus. Review of medical records for 1997 through 2006 at Mayo Clinic,
      Rochester, Minnesota, yielded 52 patients with Becker nevi, 12 of whom had an
      associated bone, vascular, neural, congenital, or other soft-tissue abnormality,
      ranging from liposarcoma to an accessory areola. CONCLUSIONS: We add to the
      literature a unique case of desmoid-type fibromatosis immediately beneath a
      Becker melanosis, which presented as a painful dimple. We hope to raise awareness
      that a Becker nevus may be associated with other abnormalities, including an
      infiltrative soft-tissue tumor. We also emphasize the importance of follow-up,
      including inspection of not only the surface but also the deep tissues underlying
      the Becker nevus.

PMID- 21173324
TI  - Extensive slow-flow vascular malformations and pulmonary hypertension.

PMID- 21173325
TI  - Erythroderma and spontaneous blistering in a 49-year-old man.

PMID- 21173326
TI  - Pruritic maculopapular dermatitis in a household.

PMID- 21173327
TI  - An unusual case of palmoplantar keratoderma.

PMID- 21173328
TI  - Generalized flesh-colored papules in a 5-year-old boy.

PMID- 21173329
TI  - The effect of initial indoor tanning with mother on current tanning patterns.

PMID- 21173330
TI  - A randomized controlled pilot study of the effects of an extra office visit on
      adherence and outcomes in atopic dermatitis.

PMID- 21173331
TI  - Failure to maximize patient adherence strategies in clinical practice.

PMID- 21173333
TI  - Multiple myeloma-associated amyloidosis presenting with acrolocalized acquired
      cutis laxa.

PMID- 21173332
TI  - Phase 1 clinical trial of intralesional injection of Candida antigen for the
      treatment of warts.

PMID- 21173334
TI  - Minoxidil-induced trichostasis spinulosa of terminal hair.

PMID- 21173335
TI  - Sporotrichoid Staphylococcus aureus infection in an immunosuppressed patient.

PMID- 21173336
TI  - HLA-B*1502 allele associated with carbamazepine-induced epidermal necrolysis.

PMID- 21173337
TI  - Regional squamous cell carcinomas following systemic sorafenib therapy and
      isolated limb infusion for regionally advanced metastatic melanoma of the limb.

PMID- 21173339
TI  - The zig-zag pattern of lentigo maligna.

PMID- 21173340
TI  - Elevated maternal soluble Gp130 and IL-6 levels and reduced Gp130 and SOCS-3
      expressions in women complicated with preeclampsia.
AB  - Increased inflammatory response plays a significant role in the vascular
      pathophysiology in preeclampsia. However, the mechanism for increased
      inflammatory response in preeclampsia is largely unknown. Interleukin (IL)-6
      levels are elevated in women with preeclampsia. IL-6 and its receptors, IL-6R and
      glycoprotein (gp)130, play a critical role in mediating antiinflammatory response
      via induction of SOCS-3 (suppressor of cytokine signaling-3). However, IL-6
      receptor levels and expressions have not been studied in preeclampsia. In this
      study, we measured IL-6 and its 2 soluble receptors, soluble IL-6R and soluble
      gp130, in maternal plasma from normal and preeclamptic pregnant women and found
      that not only IL-6 but also soluble gp130 levels were significantly higher in
      preeclamptic women than in normotensive pregnant controls. We further examined IL
      6R, gp130, and SOCS-3 expressions in maternal vessels and leukocytes and found
      that gp130 and SOCS-3 expressions were downregulated in both vessel endothelium
      and leukocytes from preeclampsia. Different patterns for IL-6R and gp130
      expressions were found. IL-6R expression was also downregulated in leukocytes
      from preeclampsia. Our results suggest that increased plasma soluble
      gp130/soluble IL-6R/IL-6 ratio and reduced membrane transsignaling gp130
      expression could contribute to decreased SOCS-3 expression and subsequent
      reduction in SOCS-3 antiinflammatory activity in women with preeclampsia. Thus,
      reduced gp130 and SOCS-3 expressions may offer, at least in part, a plausible
      explanation of reduced antiinflammatory protection in the maternal vascular
      system in preeclampsia.

PMID- 21173342
TI  - Influence of aortic pressure wave components determined noninvasively on
      myocardial oxygen demand in men and women.
AB  - Myocardial oxygen consumption is increased by arterial stiffening. It is not
      known precisely how. This study aimed to evaluate the role of the incident and
      reflected pressure wave in raising myocardial oxygen demand. Central (aortic)
      pressure waveforms were generated from radial waveforms using a generalized
      transfer function in 1628 cardiology outpatients (1038 males and 590 females).
      Aortic waveforms were used to derive measures of incident and reflected waves, as
      well as to measure mean central systolic pressure (an indicator of systolic
      ventricular load), left ventricular ejection duration, and tension time index (a
      surrogate of myocardial oxygen demand) using validated techniques. Incident and
      reflected waves were measured using the conventional and an alternative method
      (aortic flow triangulation). Relationships were tested before and after
      correction for age, height, weight, heart rate, and mean arterial pressure using
      simple and multivariate linear regression models. Analyses were conducted
      separately by gender. In both genders (according to conventional or alternative
      methods of wave measurement), both the incident and reflected wave were strong
      predictors of tension time index (P<0.001). Both pressure waves raised the mean
      central systolic pressure (P<0.001). The reflected wave (P<0.001), unlike the
      incident wave (P>0.05), was also associated with a longer cardiac ejection
      duration. Tension time index (P<0.0001), mean central systolic pressure
      (P<0.001), and ejection duration (P<0.0001) were greater in women. Changes in
      arterial properties alter the nature of pressure wave propagation and predispose
      to cardiac ischemia (especially in women).

PMID- 21173343
TI  - Dysfunction of the cholinergic anti-inflammatory pathway mediates organ damage in
      hypertension.
AB  - Inflammatory responses are associated with the genesis and progression of end
      organ damage (EOD) in hypertension. A role for the alpha7 nicotinic acetylcholine
      receptor (alpha7nAChR) in inflammation has recently been identified. We tested
      the hypothesis that alpha7nAChR dysfunction contributes to hypertensive EOD. In
      both spontaneously hypertensive rats (SHRs) and rats with abdominal aorta
      coarctation-induced hypertension, atropine-induced tachycardia was blunted
      compared with normotensive controls. Both models of hypertension were associated
      with deficits in expression of the vesicular acetylcholine transporter and the
      alpha7nAChR in cardiovascular tissues. In hypertension induced by abdominal aorta
      coarctation, deficits in aortic vesicular acetylcholine transporter and
      alpha7nAChR were present both above and below the coarctation site, indicating
      that they were independent of the level of arterial pressure itself. Hypertension
      in 40-week-old SHRs was associated with cardiac and aortic hypertrophy.
      Morphological abnormalities consistent with EOD, along with elevated tissue
      levels of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin
      1beta, and interleukin-6) were observed in the heart, kidney, and aorta. Chronic
      treatment of SHRs with the alpha7nAChR agonist PNU-282987 relieved EOD and
      inhibited tissue levels of proinflammatory cytokines and activation of nuclear
      factor kappaB. Greater serum levels of proinflammatory cytokines and more severe
      damage in the heart, aorta, and kidney were seen in alpha7nAChR(-/-) mice
      subjected to 2-kidney-1-clip surgery than in wild-type mice. A deficit in the
      cholinergic anti-inflammatory pathway appears to contribute to the pathogenesis
      of EOD in models of hypertension of varying etiology. This pathway may provide a
      new target for preventing cardiovascular disease resulting from hypertension.

PMID- 21173341
TI  - In vivo bioluminescence imaging reveals redox-regulated activator protein-1
      activation in paraventricular nucleus of mice with renovascular hypertension.
AB  - Renovascular hypertension in mice is characterized by an elevation in
      hypothalamic angiotensin II levels. The paraventricular nucleus (PVN) is a major
      cardioregulatory site implicated in the neurogenic component of renovascular
      hypertension. Increased superoxide (O(2)(-.)) production in the PVN is involved
      in angiotensin II-dependent neurocardiovascular diseases such as hypertension and
      heart failure. Here, we tested the hypothesis that excessive O(2)(-.) production
      and activation of the redox-regulated transcription factor activator protein-1
      (AP-1) in PVN contributes to the development and maintenance of renovascular
      hypertension. Male C57BL/6 mice underwent implantation of radiotelemeters,
      bilateral PVN injections of an adenovirus (Ad) encoding superoxide dismutase
      (AdCuZnSOD) or a control gene (LacZ), and unilateral renal artery clipping (2
      kidney, one-clip [2K1C]) or sham surgery. AP-1 activity was longitudinally
      monitored in vivo by bioluminescence imaging in 2K1C or sham mice that had
      undergone PVN-targeted microinjections of an Ad encoding the firefly luciferase
      (Luc) gene downstream of AP-1 response elements (AdAP-1Luc). 2K1C evoked chronic
      hypertension and an increase in O(2)(-.) production in the PVN. Viral delivery of
      CuZnSOD to the PVN not only prevented the elevation in O(2)(-.) but also
      abolished renovascular hypertension. 2K1C also caused a surge in AP-1 activity in
      the PVN, which paralleled the rise in O(2)(-.) production in this brain region,
      and this was prevented by treatment with AdCuZnSOD. Finally, Ad-mediated
      expression of a dominant-negative inhibitor of AP-1 activity in the PVN prevented
      2K1C-evoked hypertension. These results implicate oxidant signaling and AP-1
      transcriptional activity in the PVN as key mediators in the pathogenesis of
      renovascular hypertension.

PMID- 21173344
TI  - Mitogen-activated protein kinase-activated protein kinase 2 in angiotensin II
      induced inflammation and hypertension: regulation of oxidative stress.
AB  - Vascular oxidative stress and inflammation play an important role in angiotensin
      II-induced hypertension, and mitogen-activated protein kinases participate in
      these processes. We questioned whether mitogen-activated protein kinase-activated
      protein kinase 2 (MK2), a downstream target of p38 mitogen-activated protein
      kinase, is involved in angiotensin II-induced vascular responses. In vivo
      experiments were performed in wild-type and Mk2 knockout mice infused
      intravenously with angiotensin II. Angiotensin II induced a 30 mm Hg increase in
      mean blood pressure in wild-type that was delayed in Mk2 knockout mice.
      Angiotensin II increased superoxide production and vascular cell adhesion
      molecule-1 in blood vessels of wild-type but not in Mk2 knockout mice. Mk2
      knockdown by small interfering RNA in mouse mesenteric vascular smooth muscle
      cells caused a 42% reduction in MK2 protein and blunted the angiotensin II
      induced 40% increase of MK2 expression. Mk2 knockdown blunted angiotensin II
      induced doubling of intracellular adhesion molecule-1 expression, 2.4-fold
      increase of nuclear p65, and 1.4-fold increase in Ets-1. Mk2 knockdown abrogated
      the angiotensin II-induced 4.7-fold and 1.3-fold increase of monocyte
      chemoattractant protein-1 mRNA and protein. Angiotensin II enhanced reactive
      oxygen species levels (by 29%) and nicotinamide adenine dinucleotide phosphate
      oxidase activity (by 48%), both abolished by Mk2 knockdown. Reduction of MK2
      blocked angiotensin II-induced p47phox translocation to the membrane, associated
      with a 53% enhanced catalase expression. Angiotensin II-induced increase of MK2
      was prevented by the nicotinamide adenine dinucleotide phosphate oxidase
      inhibitor Nox2ds-tat. Mk2 small interfering RNA prevented the angiotensin II
      induced 30% increase of proliferation. In conclusion, MK2 plays a critical role
      in angiotensin II signaling, leading to hypertension, oxidative stress via
      activation of p47phox and inhibition of antioxidants, and vascular inflammation
      and proliferation.

PMID- 21173347
TI  - Finding pieces of the puzzle of nonresponse to cardiac resynchronization therapy.

PMID- 21173345
TI  - High dietary protein exacerbates hypertension and renal damage in Dahl SS rats by
      increasing infiltrating immune cells in the kidney.
AB  - The present study evaluated the influence and mechanism of action of dietary
      protein intake in Dahl SS hypertension and renal disease. Rats were fed
      isocaloric diets with low (6%), normal (18%), or high (30%) amounts of protein
      and 0.4% NaCl from 5 to 12 weeks of age; the NaCl content of the diets was then
      increased to 4.0% NaCl from 12 to 15 weeks of age. Rats fed the high-protein diet
      developed the highest mean arterial blood pressure and urine albumin-to
      creatinine ratio when fed the 4.0% NaCl diet (153 +/- 7 mm Hg and 8.0 +/- 2.4,
      respectively) compared to rats fed normal protein (132 +/- 3 mm Hg, 1.2 +/- 0.3)
      or low-protein (132 +/- 6 mm Hg, 0.3 +/- 0.1) diets. Significantly greater
      numbers of infiltrating T lymphocytes were observed in kidneys of SS rats fed the
      high-protein diet (18.9 +/- 3 * 105 cells) than in rats fed the low-protein diet
      (9.1 +/- 3 * 105 cells). Furthermore, treatment of SS rats fed the high-protein
      diet with the immunosuppressant agent mycophenolate mofetil (20 mg/kg per day,
      ip) significantly reduced the number of infiltrating T cells in the kidneys (from
      18.9 +/- 2.7 to 10.6 +/- 2.0 * 105 cells) while decreasing blood pressure (from
      133 +/- 3 to 113 +/- 4 mm Hg) and the albumin/creatinine ratio (from 10.9 +/- 2.3
      to 5.4 +/- 1.2). These results demonstrate that restriction of protein intake
      protects the Dahl SS rats from hypertension and kidney disease and indicates that
      infiltrating immune cells play a pathological role in Dahl SS rats fed a high
      protein diet. Moreover, the results show that hypertension in Dahl SS rats is
      sensitive to both NaCl and protein intake.

PMID- 21173346
TI  - 2011 ACCF/AHA/HRS focused update on the management of patients with atrial
      fibrillation (updating the 2006 guideline): a report of the American College of
      Cardiology Foundation/American Heart Association Task Force on Practice
      Guidelines.

PMID- 21173348
TI  - Randomized comparison of final kissing balloon dilatation versus no final kissing
      balloon dilatation in patients with coronary bifurcation lesions treated with
      main vessel stenting: the Nordic-Baltic Bifurcation Study III.
AB  - BACKGROUND: It is unknown whether the preferred 1-stent bifurcation stenting
      approach with stenting of the main vessel (MV) and optional side branch stenting
      using drug-eluting stents should be finalized by a kissing balloon dilatation
      (FKBD). Therefore, we compared strategies of MV stenting with and without FKBD.
      METHODS AND RESULTS: We randomized 477 patients with a bifurcation lesion to FKBD
      (n=238) or no FKBD (n=239) after MV stenting. The primary end point was major
      adverse cardiac events: cardiac death, non-procedure-related index lesion
      myocardial infarction, target lesion revascularization, or stent thrombosis
      within 6 months. The 6-month major adverse cardiac event rates were 2.1% and 2.5%
      (P=1.00) in the FKBD and no-FKBD groups, respectively. Procedure and fluoroscopy
      times were longer and more contrast media was needed in the FKBD group than in
      the no-FKBD group. Three hundred twenty-six patients had a quantitative coronary
      assessment. At 8 months, the rate of binary (re)stenosis in the entire
      bifurcation lesion (MV and side branch) was 11.0% versus 17.3% (P=0.11), in the
      MV was 3.1% versus 2.5% (P=0.68), and in the side branch was 7.9% versus 15.4%
      (P=0.039) in the FKBD versus no-FKBD groups, respectively. In patients with true
      bifurcation lesions, the side branch restenosis rate was 7.6% versus 20.0%
      (P=0.024) in the FKBD and no-FKBD groups, respectively. CONCLUSIONS: MV stenting
      strategies with and without FKBD were associated with similar clinical outcomes.
      FKBD reduced angiographic side branch (re)stenosis, especially in patients with
      true bifurcation lesions. The simple no-FKBD procedures resulted in reduced use
      of contrast media and shorter procedure and fluoroscopy times. Long-term data on
      stent thrombosis are needed. Clinical Trial Registration- URL:
      http://clinicaltrials.gov. Unique identifier: NCT00914199.

PMID- 21173349
TI  - Survival comparison of the Ross procedure and mechanical valve replacement with
      optimal self-management anticoagulation therapy: propensity-matched cohort study.
AB  - BACKGROUND: It is suggested that in young adults the Ross procedure results in
      better late patient survival compared with mechanical prosthesis implantation. We
      performed a propensity score-matched study that assessed late survival in young
      adult patients after a Ross procedure versus that after mechanical aortic valve
      replacement with optimal self-management anticoagulation therapy. METHODS AND
      RESULTS: We selected 918 Ross patients and 406 mechanical valve patients 18 to 60
      years of age without dissection, aneurysm, or mitral valve replacement who
      survived an elective procedure (1994 to 2008). With the use of propensity score
      matching, late survival was compared between the 2 groups. Two hundred fifty
      three patients with a mechanical valve (mean follow-up, 6.3 years) could be
      propensity matched to a Ross patient (mean follow-up, 5.1 years). Mean age of the
      matched cohort was 47.3 years in the Ross procedure group and 48.0 years in the
      mechanical valve group (P=0.17); the ratio of male to female patients was 3.2 in
      the Ross procedure group and 2.7 in the mechanical valve group (P=0.46).
      Linearized all-cause mortality rate was 0.53% per patient-year in the Ross
      procedure group compared with 0.30% per patient-year in the mechanical valve
      group (matched hazard ratio, 1.86; 95% confidence interval, 0.58 to 5.91;
      P=0.32). Late survival was comparable to that of the general German population.
      CONCLUSIONS: In comparable patients, there is no late survival difference in the
      first postoperative decade between the Ross procedure and mechanical aortic valve
      implantation with optimal anticoagulation self-management. Survival in these
      selected young adult patients closely resembles that of the general population,
      possibly as a result of highly specialized anticoagulation self-management,
      better timing of surgery, and improved patient selection in recent years.

PMID- 21173350
TI  - Can we take continuous quality improvement to the next level?

PMID- 21173352
TI  - Trends in out-of-hospital deaths due to coronary heart disease in Sweden (1991 to
      2006).
AB  - BACKGROUND: Case fatality associated with a first coronary event is often
      underestimated when only those who survive to reach a hospital are considered.
      Few studies have examined long-term trends in case fatality associated with a
      major coronary event that occurs out of the hospital. METHODS AND RESULTS: Record
      linkage documented all case subjects 35 to 84 years of age in Sweden during 1991
      to 2006 with a first major coronary event (out-of-hospital coronary death or
      hospitalization for acute myocardial infarction). Of the 384 597 cases
      identified, 111 319 (28.9%) died out of the hospital, and another 36 552 (9.5%)
      died in the hospital or within 28 days of hospitalization. From 1991 to 2006, out
      of hospital deaths as a proportion of all major coronary events declined from
      30.5% to 25.6% (adjusted mean annual decrease 2.2%, 95% confidence interval 2.1%
      to 2.4%), however, with a larger decline in 28-day case fatality in hospitalized
      cases (adjusted mean annual decrease 5.8%, 95% confidence interval 5.5% to 6.0%).
      As a result of the faster decline in in-hospital deaths, the relative
      contribution of out-of-hospital deaths to overall case fatality increased,
      particularly among younger individuals (eg, among those 35 to 54 years of age, no
      more than 10.8% of all deaths occurred in hospitalized cases during 2003-2006).
      Although female sex (odds ratio 0.85, 95% confidence interval 0.83 to 0.87) and
      older age (odds ratio 0.972, 95% confidence interval 0.971 to 0.974 per year)
      were associated with lower risk for initial out-of-hospital death, each
      successive calendar year was associated with increased risk (odds ratio 1.041,
      95% confidence interval 1.038 to 1.044). CONCLUSIONS: The great majority of all
      fatal coronary events occur outside the hospital, and this proportion is
      increasing, particularly among younger individuals.

PMID- 21173351
TI  - Mitogen-activated protein kinase inhibitors improve heart function and prevent
      fibrosis in cardiomyopathy caused by mutation in lamin A/C gene.
AB  - BACKGROUND: Mutations in the lamin A/C gene, LMNA, can cause dilated
      cardiomyopathy. We have shown abnormal activation of the extracellular signal
      regulated kinase (ERK) and the c-jun N-terminal kinase (JNK) branches of the
      mitogen-activated protein kinase signaling cascade in hearts from
      Lmna(H222P/H222P) mice that develop dilated cardiomyopathy. We recently showed
      that partial inhibition of ERK and JNK signaling before the onset of
      cardiomyopathy in Lmna(H222P/H222P) mice prevented the development of left
      ventricle dilatation and decreased cardiac ejection fraction at a time when they
      occurred in untreated mice. METHODS AND RESULTS: To determine whether
      pharmacological inhibitors of ERK and JNK signaling could be clinically useful to
      treat cardiomyopathy caused by LMNA mutation, we administered them to
      Lmna(H222P/H222P) mice after they developed left ventricular dilatation and
      decreased ejection fraction. Lmna(H222P/H222P) mice were treated with ERK and JNK
      signaling inhibitors from 16 to 20 or, in pilot experiments, 19 to 24 weeks of
      age. The inhibitors blocked increased expression of RNAs encoding natriuretic
      peptide precursors and proteins involved in sarcomere architecture that occurred
      in placebo-treated mice. Echocardiography and histological analysis demonstrated
      that treatment prevented left ventricular end-systolic dilatation, increased
      ejection fraction, and decreased myocardial fibrosis. CONCLUSION: Inhibitors of
      ERK and JNK signaling could potentially be used to treat humans with
      cardiomyopathy caused by LMNA mutations.

PMID- 21173353
TI  - Relative merits of left ventricular dyssynchrony, left ventricular lead position,
      and myocardial scar to predict long-term survival of ischemic heart failure
      patients undergoing cardiac resynchronization therapy.
AB  - BACKGROUND: The relative merits of left ventricular (LV) dyssynchrony, LV lead
      position, and myocardial scar to predict long-term outcome after cardiac
      resynchronization therapy remain unknown and were evaluated in the present study.
      METHODS AND RESULTS: In 397 ischemic heart failure patients, 2-dimensional
      speckle tracking imaging was performed, with comprehensive assessment of LV
      radial dyssynchrony, identification of the segment with latest mechanical
      activation, and detection of myocardial scar in the segment where the LV lead was
      positioned. For LV dyssynchrony, a cutoff value of 130 milliseconds was used.
      Segments with <16.5% radial strain in the region of the LV pacing lead were
      considered to have extensive myocardial scar (>50% transmurality, validated in a
      subgroup with contrast-enhanced magnetic resonance imaging). The LV lead position
      was derived from chest x-ray. Long-term follow-up included all-cause mortality
      and hospitalizations for heart failure. Mean baseline LV radial dyssynchrony was
      133+/-98 milliseconds. In 271 patients (68%), the LV lead was placed at the
      latest activated segment (concordant LV lead position), and the mean value of
      peak radial strain at the targeted segment was 18.9+/-12.6%. Larger LV radial
      dyssynchrony at baseline was an independent predictor of superior long-term
      survival (hazard ratio, 0.995; P=0.001), whereas a discordant LV lead position
      (hazard ratio, 2.086; P=0.001) and myocardial scar in the segment targeted by the
      LV lead (hazard ratio, 2.913; P<0.001) were independent predictors of worse
      outcome. Addition of these 3 parameters yielded incremental prognostic value over
      the combination of clinical parameters. CONCLUSIONS: Baseline LV radial
      dyssynchrony, discordant LV lead position, and myocardial scar in the region of
      the LV pacing lead were independent determinants of long-term prognosis in
      ischemic heart failure patients treated with cardiac resynchronization therapy.
      Larger baseline LV dyssynchrony predicted superior long-term survival, whereas
      discordant LV lead position and myocardial scar predicted worse outcome.

PMID- 21173355
TI  - Marathon rat: myocardial remodeling in an animal model of vigorous endurance
      exercise and implications for humans.

PMID- 21173354
TI  - Autologous cardiomyotissue implantation promotes myocardial regeneration,
      decreases infarct size, and improves left ventricular function.
AB  - BACKGROUND: Cell therapy for myocardial infarction (MI) may be limited by poor
      cell survival and lack of transdifferentiation. We report a novel technique of
      implanting whole autologous myocardial tissue from preserved myocardial regions
      into infarcted regions. METHODS AND RESULTS: Fourteen rats were used to optimize
      cardiomyotissue size with peritoneal wall implantation (300 MUm identified as
      optimal size). Thirty-nine pigs were used to investigate cardiomyotissue
      implantation in MI induced by left anterior descending balloon occlusion (10
      animals died; male-to-female transplantation for tracking with in situ
      hybridization for Y chromosome, n=4 [2 donors and 2 MI animals]; acute MI
      implantation cohort at 1 hour, n=13; and healed MI implantation at 2 weeks,
      n=12). Assessment included echocardiography, magnetic resonance imaging,
      hemodynamics, triphenyltetrazolium chloride staining, and histological and
      molecular analyses. Tracking studies demonstrated viable implants with donor
      cells interspersed in the adjacent myocardium with gap junctions and desmosomes.
      In the acute MI cohort, treated animals compared with controls had improved
      perfusion by magnetic resonance imaging (1.2+/-0.01 versus 0.86+/-0.05; P<0.01),
      decreased MI size (magnetic resonance imaging: left ventricle, 2.2+/-0.5% versus
      5.4+/-1.5%, P=0.04; triphenyltetrazolium chloride: anterior wall, 10.3+/-4.6%
      versus 28.9+/-5.8%, P<0.03), and improved contractility (dP/dt, 1235+/-215 versus
      817+/-817; P<0.05). In the healed MI cohort, treated animals had less decline in
      ejection fraction between 2 and 4 week assessment (-3+/-4% versus -13+/--4%;
      P<0.05), less decline in +/-dP/dt, and smaller MI (triphenyltetrazolium chloride,
      21+/-11% versus 3+/-8%; P=0.006) than control animals. Infarcts in the treated
      animals contained more mdr-1(+) cells and fewer c-kit(+) cells with a trend for
      decreased expression of matrix metalloproteinase-2 and increased expression of
      tissue inhibitor of metalloproteinase-2. CONCLUSION: Autologous cardiomyotissue
      implanted in an MI area remains viable, exhibits electromechanical coupling,
      decreases infarct size, and improves left ventricular function.

PMID- 21173356
TI  - Cardiac arrhythmogenic remodeling in a rat model of long-term intensive exercise
      training.
AB  - BACKGROUND: Recent clinical studies suggest that endurance sports may promote
      cardiac arrhythmias. The aim of this study was to use an animal model to evaluate
      whether sustained intensive exercise training induces potentially adverse
      myocardial remodeling and thus creates a potential substrate for arrhythmias.
      METHODS AND RESULTS: Male Wistar rats were conditioned to run vigorously for 4,
      8, and 16 weeks; time-matched sedentary rats served as controls. Serial
      echocardiograms and in vivo electrophysiological studies at 16 weeks were
      obtained in both groups. After euthanasia, ventricular collagen deposition was
      quantified by histological and biochemical studies, and messenger RNA and protein
      expression of transforming growth factor-beta1, fibronectin-1, matrix
      metalloproteinase-2, tissue inhibitor of metalloproteinase-1, procollagen-I, and
      procollagen-III was evaluated in all 4 cardiac chambers. At 16 weeks, exercise
      rats developed eccentric hypertrophy and diastolic dysfunction, together with
      atrial dilation. In addition, collagen deposition in the right ventricle and
      messenger RNA and protein expression of fibrosis markers in both atria and right
      ventricle were significantly greater in exercise than in sedentary rats at 16
      weeks. Ventricular tachycardia could be induced in 5 of 12 exercise rats (42%)
      and only 1 of 16 sedentary rats (6%; P=0.05). The fibrotic changes caused by 16
      weeks of intensive exercise were reversed after an 8-week exercise cessation.
      CONCLUSIONS: In this animal model, we documented cardiac fibrosis after long-term
      intensive exercise training, together with changes in ventricular function and
      increased arrhythmia inducibility. If our findings are confirmed in humans, the
      results would support the notion that long-term vigorous endurance exercise
      training may in some cases promote adverse remodeling and produce a substrate for
      cardiac arrhythmias.

PMID- 21173358
TI  - Recurrent sinus arrest and asystole due to breath-holding spell in a toddler;
      recovery with levetiracetam-therapy.

PMID- 21173357
TI  - Secondary prevention after coronary artery bypass graft surgery: findings of a
      national randomized controlled trial and sustained society-led incorporation into
      practice.
AB  - BACKGROUND: Despite evidence supporting the use of aspirin, beta-blockers,
      angiotensin-converting enzyme inhibitors, and lipid-lowering therapies in
      eligible patients, adoption of these secondary prevention measures after coronary
      artery bypass grafting has been inconsistent. We sought to rigorously test on a
      national scale whether low-intensity continuous quality improvement interventions
      can be used to speed secondary prevention adherence after coronary artery bypass
      grafting. METHODS AND RESULTS: A total of 458 hospitals participating in the
      Society of Thoracic Surgeons National Cardiac Database and treating 361 328
      patients undergoing isolated coronary artery bypass grafting were randomized to
      either a control or an intervention group. The intervention group received
      continuous quality improvement materials designed to influence the prescription
      of the secondary prevention medications at discharge. The primary outcome measure
      was discharge prescription rates of the targeted secondary prevention medications
      at intervention versus control sites, assessed by measuring preintervention and
      postintervention site differences. Prerandomization treatment patterns and
      baseline data were similar in the control (n=234) and treatment (n=224) groups.
      Individual medication use and composite adherence increased over 24 months in
      both groups, with a markedly more rapid rate of adherence uptake among the
      intervention hospitals and a statistically significant therapy hazard ratio in
      the intervention versus control group for all 4 secondary prevention medications.
      CONCLUSIONS: Provider-led, low-intensity continuous quality improvement efforts
      can improve the adoption of care processes into national practice within the
      context of a medical specialty society infrastructure. The findings of the
      present trial have led to the incorporation of study outcome metrics into a
      medical society rating system for ongoing quality improvement.

PMID- 21173359
TI  - Letter by Meurin et al regarding article, "Early surgery versus conventional
      treatment in asymptomatic very severe aortic stenosis".

PMID- 21173360
TI  - Letter by Fresco regarding article "Primary angioplasty versus fibrinolysis in
      acute myocardial infarction: long-term follow-up in the Danish Acute Myocardial
      Infarction 2 trial".

PMID- 21173362
TI  - Glucose-lowering targets for patients with cardiovascular disease: focus on
      inpatient management of patients with acute coronary syndromes.

PMID- 21173361
TI  - Molecular pathways underlying cardiac remodeling during pathophysiological
      stimulation.

PMID- 21173363
TI  - Images in cardiovascular disease. Pulmonary vein stenosis after lung
      transplantation successfully treated with stent implantation.

PMID- 21173364
TI  - We show pictures, they show curves.

PMID- 21173365
TI  - Decision making for the extent of thyroidectomy in the patient with atypical
      cytologic results.
AB  - OBJECTIVE: to identify additional preoperative factors that could reliably be
      used to aid in determining the appropriate extent of thyroidectomy. DESIGN:
      retrospective chart review. SETTING: tertiary care academic hospital. PATIENTS:
      two hundred consecutively treated patients who underwent thyroid surgery after
      having a fine-needle aspiration biopsy procedure yielding a specimen that met the
      criteria for atypical cytologic features. MAIN OUTCOME MEASURE: final
      histopathologic diagnosis of malignant vs benign disease. RESULTS: the final
      diagnosis was benign in 42.5% of patients and malignant in 57.5%. The presence of
      microcalcifications within the nodule on ultrasonography (US) was significantly
      associated with a higher risk of malignant disease (relative risk = 1.31, P =
      .04). When examined individually, age, sex, family history of thyroid malignant
      disease, exposure to head and neck irradiation, nodule size, rim enhancement on
      US, and intranodular vascularity on US were not significantly associated with an
      increased risk of malignant disease. Mulivariate stepwise logistic regression
      modeling was used to identify a model that could reliably predict a higher
      probability of malignant disease. The final model determined that patients with
      microcalcifications on US and a nodule of 2.0 cm or larger had a 74.3% risk of
      malignant disease vs a 47.5% risk in patients with no microcalcifications and a
      nodule smaller than 2.0 cm. This difference was statistically significant. When
      the predicted probabilities of malignant disease were compared with the observed
      probabilities, the goodness-of-fit test revealed no significant difference (P =
      .95). CONCLUSION: microcalcifications and nodule size can be used to risk
      stratify patients with an atypical fine-needle aspiration biopsy result and aid
      in determining the appropriate extent of thyroidectomy.

PMID- 21173366
TI  - Surgical practice patterns in the treatment of papillary thyroid microcarcinoma.
AB  - BACKGROUND: recently, there has been a debate regarding total thyroidectomy vs
      hemithyroidectomy for papillary thyroid microcarcinoma (PTMC). OBJECTIVE: to
      determine whether there were significant differences in the treatment of PTMC
      depending on a physician's experience, age, training, and location. METHODS: a 10
      question survey was distributed to otolaryngologists, general surgeons, and
      endocrine surgeons. It included 4 clinical scenarios, 2 questions querying
      clinical reasoning, and 4 demographic questions (training, surgical volume,
      location, and age). The demographic variables were used to analyze responses to
      the 4 clinical scenarios with bivariate and multivariate statistics. RESULTS: a
      total of 438 responders completed the survey. Given a single subcentimeter PTMC,
      70.3% of surgeons recommended no further surgery after a hemithyroidectomy, yet
      29.7% believed that completion thyroidectomy was necessary. Otolaryngologists
      chose total thyroidectomy more frequently, as did surgeons from the South and
      West. Given PTMC with lymphatic invasion, 392 (89.5%) responders recommended
      completion thyroidectomy, with otolaryngologists again more inclined toward
      completion surgery. Given multifocal PTMC, 85.4% chose completion thyroidectomy,
      with surgeons in the South and West recommending total thyroidectomy more
      frequently compared with those in the Northeast. Improved survival, surgeon
      preference, and need for thyroid suppression were rated relatively insignificant.
      Ease of patient follow-up and multifocality of disease were judged very
      significant. Influence from national guidelines and current literature was rated
      as only somewhat or minimally significant. CONCLUSIONS: in this survey, most
      surgeons seemed to follow national guidelines regarding the surgical treatment of
      PTMC. However, significant differences in the treatment and perception of PTMC
      exist based on surgical training and location.

PMID- 21173367
TI  - Volume-based trends in thyroid surgery.
AB  - OBJECTIVE: to characterize contemporary patterns of thyroid surgical care and
      variables associated with access to high-volume care. DESIGN: cross-sectional
      analysis. SETTING: maryland Health Service Cost Review Commission database.
      PATIENTS: adults who underwent surgery for thyroid disease in Maryland between
      January 1, 1990, and July 1, 2009. RESULTS: overall, 21 270 thyroid surgical
      procedures were performed by 1034 surgeons at 51 hospitals. Procedures performed
      by high-volume surgeons increased from 15.7% in 1990-1999 to 30.9% in 2000-2009
      (odds ratio [OR], 3.69; P < .001), while procedures performed at high-volume
      hospitals increased from 11.9% to 22.7% (3.46; P < .001). High-volume surgeons
      were more likely to perform total thyroidectomy (OR, 2.50; P < .001) and neck
      dissection (1.86; P < .001), had a shorter length of hospitalization (0.44; P <
      .001), and had a lower incidence of recurrent laryngeal nerve injury (0.46; P =
      .002), hypocalcemia (0.62; P < .001), and thyroid cancer surgery (0.89; P = .01).
      After controlling for other variables, thyroid surgery in 2000-2009 was
      associated with high-volume surgeons (OR, 1.76; P < .001), high-volume hospitals
      (2.93; P < .001), total thyroidectomy (2.67; P < .001), and neck dissection
      (1.28; P = .02) but was less likely to be performed for cancer (0.83; P < .001).
      CONCLUSIONS: the proportion of thyroid surgical procedures performed by high
      volume surgeons and in high-volume hospitals increased significantly from 1990
      1999 to 2000-2009, with an increase in total thyroidectomy and neck dissection.
      Surgeon volume was significantly associated with complication rates. Thyroid
      cancer surgery was less likely to be performed by high-volume surgeons and in
      2000-2009 despite an increase in surgical cases. Further investigation is needed
      to identify factors contributing to this trend.

PMID- 21173368
TI  - Blood transfusion prediction in patients undergoing major head and neck surgery
      with free-flap reconstruction.
AB  - OBJECTIVE: to develop a clinically useful perioperative blood transfusion
      prediction model for patients undergoing a major head and neck surgical procedure
      requiring free-flap reconstruction. DESIGN: retrospective observational study.
      SETTING: tertiary care university-affiliated teaching hospital (University Health
      Network, Toronto, Ontario, Canada). PATIENTS: all patients with a head and neck
      malignant neoplasm undergoing major head and neck surgery requiring free-flap
      reconstruction. MAIN OUTCOME MEASURE: perioperative single-unit red blood cell
      transfusion. RESULTS: all the preoperative variables were tested for an
      association with perioperative blood transfusion using univariable and
      multivariable analyses. After multivariable regression analysis, the following
      preoperative variables were found to be significantly associated with
      perioperative transfusion: sex, body mass index, T stage, preoperative hemoglobin
      level, and type of free-flap reconstruction used (ie, osseous vs nonosseous). The
      regression model was used to develop a transfusion risk score. Receiver operating
      characteristic curve analysis confirmed adequate discrimination of risk using the
      transfusion risk score. CONCLUSIONS: we have developed a reliable model for
      predicting perioperative blood transfusion requirements in patients undergoing
      major head and neck surgery requiring free-flap reconstruction. This model can be
      used for accurate preoperative risk stratification.

PMID- 21173369
TI  - Prereferral head and neck cancer treatment: compliance with national
      comprehensive cancer network treatment guidelines.
AB  - OBJECTIVE: to evaluate the prereferral treatment of patients referred to our
      tertiary care center with recurrent or persistent head and neck cancer for
      compliance with National Comprehensive Cancer Network (NCCN) guidelines. DESIGN:
      a prospective recruitment and retrospective chart review. PATIENTS: the study
      included new patients identified at multidisciplinary treatment planning
      conference from October 1, 2008, to February 1, 2009, who had received prior
      treatment at an outside institution and presented to our department with
      recurrent or persistent disease. MAIN OUTCOME MEASURES: all facets of prior care
      were examined, including the time from initial symptoms to diagnosis and whether
      their prereferral treatment was compliant with or deviated from NCCN guidelines
      for head and neck cancer. RESULTS: a total of 566 consecutive new patients were
      identified, of whom 107 (18.9%) had persistent or recurrent disease. The average
      time from first presentation with initial symptoms to diagnosis among patients
      who presented with persistent disease was 23.8 weeks. Nearly half of the patients
      who presented with persistent or recurrent disease had either endocrine (21.5%)
      or cutaneous (24.2%) primary cancers, with the rest of the cases being
      distributed among 10 other sites. Of the patients who presented with recurrent or
      persistent disease, 43.0% had prereferral care that was noncompliant with NCCN
      guidelines. Of these patients, 58.7% had inadequate surgical management, 15.2%
      were treated for the wrong diagnosis, 10.9% received inadequate adjuvant therapy,
      4.4% received inadequate radiotherapy, and 10.9% refused indicated recommended
      treatment. CONCLUSIONS: significant deviation from NCCN guidelines for head and
      neck cancer treatment was observed in the cohort of study patients. The failure
      to administer adjuvant therapy when indicated by NCCN guidelines is particularly
      concerning. Economic and noneconomic costs, including lost wages, cost of "do
      over" therapy, and potentially diminished survival, are substantial. Measures to
      ensure that patients receive therapy according to guidelines should be a national
      priority.

PMID- 21173370
TI  - Quality and performance indicators in an academic department of head and neck
      surgery.
AB  - OBJECTIVE: to create a method for assessing physician performance and care
      outcomes that are adjusted for procedure acuity and patient comorbidity. DESIGN:
      between 2004 and 2008 surgical procedures performed by 10 surgeons were
      stratified into high-acuity procedures (HAPs) and low-acuity procedures (LAPs).
      Risk adjustment was made for comorbid conditions examined singly or in groups of
      2 or more. SETTING: a tertiary care medical center. PATIENTS: a total of 2618
      surgical patients. MAIN OUTCOME MEASURES: performance measures included length of
      stay; return to operating room within 7 days of surgery; and the occurrence of
      mortality, hospital readmission, transfusion, and wound infection within 30 days
      of surgery. RESULTS: the transfusion rate was 2.7% and 40.6% for LAPs and HAPs,
      respectively. Wound infection rates were 1.4% for LAPs vs 14.1% for HAPs, while
      30-day mortality rate was 0.3% and 1.6% for LAPs and HAPs, respectively. The mean
      (SD) hospital stay for LAPs was 2.1 (3.6) vs 10.5 (7.0) days for HAPs. Negative
      performance factors were significantly higher for patients who underwent HAPs and
      had comorbid conditions. Differences among surgeons significantly affect the
      incidence of negative performance indicators. Factors affecting performance
      measures were procedure acuity, the surgeon, and comorbidity, in order of
      decreasing significance. Surgeons were ranked low, middle, and high based on
      negative performance indicators. CONCLUSIONS: performance measures following
      oncologic procedures were significantly affected by comorbid conditions and by
      procedure acuity. Although the latter most strongly affects quality and
      performance indicators, both should weigh heavily in physician comparisons. The
      incidence of negative performance indicators was also influenced by the
      individual surgeon. These data may serve as a tool to evaluate and improve
      physician performance and outcomes and to develop risk-adjusted benchmarks.
      Ultimately, reimbursement may be tied to quantifiable measures of physician and
      institutional performance.

PMID- 21173371
TI  - Postoperative radiotherapy in head and neck mucosal melanoma: a GETTEC study.
AB  - OBJECTIVE: to report patterns of failure according to treatment modality, with an
      emphasis on the role of postoperative radiotherapy in patients with localized
      head and neck mucosal melanoma (HNMM) treated during a 28-year period in a multi
      institutional setting. DESIGN: retrospective review. SETTING: french medical
      institutions. PATIENTS: a total of 160 patients with nonmetastatic HNMM treated
      from 1980 through 2008. INTERVENTIONS: treatment modality consisted of surgery
      alone (hereinafter, S group) (n = 82 patients) or with postoperative radiotherapy
      (hereinafter, SRT group) (n = 78). Patients and tumor characteristics were
      similar in the 2 groups. There was a nonsignificant trend (P = .11) for more
      locally advanced tumor stage (38.9%) in the SRT group compared with the S group
      (24.5%). RESULTS: patients in the S group had an increased probability of
      locoregional recurrence as a first event (55.6%) compared with those in the SRT
      group (29.9%; P < .01). After adjusting for tumor stage (T1/T2 vs T3/T4), the
      subdistribution hazard ratio of locoregional relapse was 0.31, (95% confidence
      interval [CI], 0.15-0.61; P < .01).The rate of distant metastasis as a first
      event was significantly higher in the SRT group (40.6%) compared with the S group
      (19.9%; P = .01). Regardless of their treatment, patients who had a locoregional
      relapse during follow-up had an increased risk of subsequent distant metastasis
      (hazard ratio, 3.07; 95% CI, 1.65-5.67) and death (hazard ratio, 3.01; 95% CI,
      1.91-4.78). CONCLUSIONS: this large retrospective study suggests that
      postoperative radiotherapy improves the locoregional control of HNMM. The higher
      rate of distant metastasis was due to more advanced disease in the SRT group.

PMID- 21173372
TI  - Factors associated with long-term speech and swallowing outcomes after
      chemoradiotherapy for locoregionally advanced head and neck cancer.
AB  - OBJECTIVE: to identify factors that influence patient-centered measures of speech
      and swallowing function after successful use of chemoradiotherapy to treat
      cancers of the head and neck. DESIGN: patients previously enrolled in a phase 2
      trial using induction chemotherapy consisting of carboplatin and paclitaxel
      followed by chemoradiotherapy with paclitaxel, fluorouracil, hydroxyurea, and 1
      of 3 radiation dose levels were assigned speaking and swallowing scores at follow
      up ranging from 1 to 4, with 1 representing normal speech or swallowing and 4
      representing significant sustained deficits. PATIENTS: one hundred eighty-four
      patients with locoregionally advanced head and neck cancer. MAIN OUTCOME
      MEASURES: speech and swallowing function after chemoradiotherapy. RESULTS: of the
      222 patients originally enrolled in the trial, 184 were alive and free of
      locoregional recurrence at the outset of this study. Of these eligible patients,
      163 (88.6%) were assigned a speaking score of 1 through 4 at an average of 34.8
      (range, 1.5-76.4) months after completion of treatment, whereas 166 patients
      (90.2%) were assigned a swallowing score of 1 through 4 at an average of 34.5
      (range, 1.0-76.4) months after completion of treatment. Most patients (84.7% with
      speaking scores and 63.3% with swallowing scores) had no residual deficit and
      were assigned scores of 1. Factors that were associated with worse speaking
      outcomes included female sex, smoking history, hypopharyngeal or laryngeal
      primary sites, and poor response to induction chemotherapy; factors associated
      with worse swallowing outcomes included advanced patient age, poor performance
      status, primary site, and neck dissection. CONCLUSIONS: among patients
      successfully treated for locoregionally advanced cancers of the head and neck,
      several factors correlate with speaking and swallowing outcomes. Because advances
      in therapy have led to improved survival in these patients, understanding and
      controlling adverse effects of treatment should continue to be an active area of
      investigation.

PMID- 21173373
TI  - Predicting the prognosis of oral squamous cell carcinoma after first recurrence.
AB  - OBJECTIVES: to describe the clinicopathologic features of oral squamous cell
      carcinoma in patients who develop locoregional recurrence of disease, to identify
      factors that predict prognosis in the subset of patients treated with salvage
      surgery, and to determine the adjusted effect of time to recurrence. DESIGN:
      cohort study. SETTING: a head and neck cancer institute in Sydney, New South
      Wales, Australia. PATIENTS: a total of 77 patients who underwent salvage surgery
      for oral squamous cell carcinoma that had been treated initially by surgery,
      radiotherapy, or surgery with postoperative radiotherapy. MAIN OUTCOME MEASURES:
      univariable and multivariable analysis of clinical and pathologic risk factors.
      RESULTS: median time to recurrence from initial treatment was 7.5 months (range,
      0.9-143.9 mo), with 86% of recurrences occurring within the first 24 months.
      Surgical salvage was attempted in 77 patients who had experienced recurrence at
      the primary site (n = 39), ipsilateral neck (n = 27), and contralateral neck (n =
      11). Time to recurrence, initial treatment modality, and site of failure were
      independent prognostic variables. CONCLUSIONS: the relationship of these
      prognostic variables displays a dynamic interaction. Initial combined-modality
      treatment and shorter time to recurrence were associated with worse outcome,
      while the effect of site of recurrence (local vs regional) was dependent on an
      interaction with the time to recurrence. The result of this interaction was that
      local recurrence was worse for those who experienced it early (eg, <6 mo after
      the initial treatment) and nodal recurrence was worse for those who experienced
      it late (eg, >= 6 mo after the intial treatment).

PMID- 21173374
TI  - Factors predicting outcome in malignant minor salivary gland tumors of the
      oropharynx.
AB  - OBJECTIVES: to report our experience in the care of patients with minor salivary
      gland cancers occurring only in the oropharynx and to determine factors
      predictive of outcome. DESIGN: Retrospective analysis. SETTING: memorial Sloan
      Kettering Cancer Center. PATIENTS: sixty-seven patients with malignant minor
      salivary gland tumors were identified from a preexisting database of patients
      with cancers of the oropharynx between January 1985 and December 2005. MAIN
      OUTCOME MEASURES: overall survival, disease-specific survival, and recurrence
      free survival were calculated by the Kaplan-Meier method. Factors predictive of
      outcome were identified by univariate and multivariate analyses. RESULTS: the
      most common histologic types were mucoepidermoid carcinoma in 26 patients (39%),
      adenoid cystic carcinoma in 16 (24%), adenocarcinoma in 16 (24%), and malignant
      mixed tumor in 7 (10%). The tumors were located in the base of the tongue in 41
      patients (61%), soft palate in 20 (30%), and tonsil in 6 (9%). With a median
      follow-up time of 86 months (range, 12-249 months), overall outcomes at 5 and 10
      years were overall survival, 80% and 53%; disease-specific survival, 87% and 67%;
      and recurrence-free survival, 69% and 60%, respectively. Tumor recurred in 20
      patients (34%); 12 of these patients had locoregional failure and 15 developed
      distant metastases. Multivariate analyses showed that clinical T stage, anatomic
      subsite, and margin status were independent predictors for overall survival; T
      stage and margin status were independent predictors for locoregional recurrence
      free survival. CONCLUSION: clinical T stage, anatomic subsite, and margin status
      are independent predictors of outcome of patients with minor salivary gland
      cancers of the oropharynx.

PMID- 21173375
TI  - Transoral robotic-assisted surgery for head and neck squamous cell carcinoma: one
      and 2-year survival analysis.
AB  - OBJECTIVE: to report 2-year survival outcomes for head and neck squamous cell
      carcinoma using transoral robotic-assisted resection. DESIGN: prospective case
      study. SETTING: two tertiary care centers. PATIENTS: eighty-nine patients from 2
      tertiary care centers (University of Alabama at Birmingham and the Mayo Clinic in
      Rochester, Minnesota) with head and neck squamous cell carcinoma of all stages
      and subsites, who underwent transoral robotic-assisted resection between March
      2007 and December 2008, with a median follow-up time of 26 months. MAIN OUTCOME
      MEASURES: disease-free survival, cancer recurrence, and gastrostomy tube
      dependence RESULTS: seventy-one patients had T1 (n = 29) or T2 (n = 42) tumors
      while 18 patients had T3 (n = 8) or T4 (n = 10) tumors. There were 24 patients
      with overall stage I or II disease and 65 with stage III or IV disease. At the
      time of the last follow-up visit (median, 26 months), there had been a total of
      11 patients with recurrent cancer: 3 with local; 7, regional (2 of whom also had
      distant metastases); and 1, distant. Seven patients were treated for recurrent
      disease. Eighty-two patients had no evidence of disease, 1 patient died of the
      disease, 2 died of other disease, and 4 were alive with disease at the last
      follow-up visit. Results of Kaplan-Meier survival analysis showed that the 2-year
      recurrence-free survival rate for the cohort was 86.5%. None of the patients were
      gastrostomy tube dependent at the last follow-up visit. CONCLUSION: the 2-year
      functional and oncologic results justify the continued treatment of select
      patients with head and neck squamous cell carcinoma with robotic-assisted
      surgical resection.

PMID- 21173376
TI  - Toll-like Receptors in Regulatory T Cells of Patients With Head and Neck Cancer.
AB  - OBJECTIVE: to investigate the role of Toll-like receptor (TLR) signaling and T
      regulatory (T-reg) cells in patients with head and neck squamous cell carcinoma
      (HNSCC). DESIGN: multicolor flow cytometry was used to study the frequency and
      phenotype of CD4(+)CD25(+)CD127(-) T-reg cells and CD4(+)CD25(-)CD127(+) T
      effector (T-eff) cells in peripheral blood mononuclear cells (PBMCs). SETTING:
      all patients were seen at the outpatient clinic at the Department of
      Otorhinolaryngology at the University of Duisburg-Essen from March 1, 2009,
      through December 31, 2009. PATIENTS: eleven patients with HNSCC and 10 healthy
      donors (HDs) were studied. T-reg and T-eff cells were isolated from PBMCs using a
      magnetic bead-activated cell-sorting technique. MAIN OUTCOME MEASURES:
      proliferation of T-eff cells and suppressor activity of T-reg cells were assessed
      in functional assays after preincubation with the TLR4 ligand heat shock protein
      60 or lipopolysaccharide in the presence or absence of neutralizing antibody
      against TLR4. RESULTS: frequency of T-reg cells in PBMCs was strongly increased
      in patients with HNSCC vs HDs. Isolation of T-reg cells from PBMCs of patients
      with HNSCC showed a significantly higher expression of TLR4, TLR6, TLR9, and
      TLR10 compared with HDs, whereas TLR2 was not detectable. After incubation with
      heat shock protein 60 or lipopolysaccharide, the suppressive function of T-reg
      cells was significantly increased (1.14- and 1.44-fold, respectively), whereas
      the proliferation capacity of T-eff cells remained unchanged. This effect was
      reversed after TLR4 inhibition on T-reg cells. CONCLUSION: the TLR ligation on T
      reg cells may contribute to tumor-mediated immune suppression by enhancing their
      suppressive activity.

PMID- 21173377
TI  - Metastatic potential of cancer stem cells in head and neck squamous cell
      carcinoma.
AB  - OBJECTIVE: to design in vitro and in vivo models of metastasis to study the
      behavior of cancer stem cells (CSCs) in head and neck squamous cell carcinoma
      (HNSCC). DESIGN: cells were sorted for CD44 expression using flow cytometry.
      Sorted cells were used in an in vitro invasion assay. For in vivo studies, CSCs
      and non-CSCs were injected into the tail veins of mice, and lungs were either
      harvested or imaged to evaluate for lesions. RESULTS: in vitro, CD44(high) cells
      were more motile but not more invasive than CD44(low) cells. In vivo, 8 of 17
      mice injected with CD44(high) cells and 0 of 17 mice injected with CD44(low)
      cells developed lung lesions. Two of the lesions arose from CSCs from a primary
      tumor and 6 from CSCs from HNSCC cell lines. CONCLUSIONS: in vitro, CSCs do not
      have an increased ability to invade through basement membrane, but they migrate
      more efficiently through a porous barrier. In contrast, CSCs efficiently formed
      lung lesions in vivo, whereas non-CSCs did not give rise to any distant disease.
      This phenomenon could be due to the enhanced migratory capacity of CSCs, which
      may be more important than basement membrane degradation in vivo.

PMID- 21173378
TI  - Correlation of cellular immunity with human papillomavirus 16 status and outcome
      in patients with advanced oropharyngeal cancer.
AB  - OBJECTIVE: to determine whether the favorable outcome associated with human
      papillomavirus (HPV) 16-positive oropharyngeal cancer is related to a patient's
      adaptive immunity. SETTING: academic medical center. PATIENTS: forty-seven of 66
      previously untreated patients (6 of 20 patients with stage III and 41 of 46 with
      stage IV cancer) in a prospective clinical trial of chemoradiotherapy.
      INTERVENTION: all patients were treated with a single course of neoadjuvant
      chemotherapy followed by either surgery (for nonresponders) or chemoradiotherapy.
      MAIN OUTCOME MEASURES: pretreatment levels (percentages and absolute counts) of
      CD3, CD4, CD8, natural killer, and B cells and overall white blood cell counts
      were measured by flow cytometry. Correlations of subsets with HPV-16 status,
      tumor subsite, cancer stage, T class, N class, smoking status, performance
      status, sex, response to chemoradiotherapy, p53 mutation type, epidermal growth
      factor receptor expression, and disease-specific and overall survival were
      determined. RESULTS: after a median follow-up of 6.6 years, improved survival was
      associated with an elevated percentage of CD8 cells (P = .04), a low CD4:CD8
      ratio (P = .01), low epidermal growth factor receptor expression (P = .002), and
      HPV status (P = .02). The percentage of CD8 cells was significantly higher (P =
      .04) and the CD4:CD8 ratio was significantly lower (P = .02) in HPV-16-positive
      patients. A higher percentage of CD8 cells was associated with response to
      induction chemotherapy (P = .02) and complete tumor response after
      chemoradiotherapy (P = .045). CONCLUSION: these findings confirm previous
      correlations of outcome with circulating CD8 cell levels and support the
      conjecture that improved adaptive immunity may play a role in the favorable
      prognosis of patients with HPV-16-positive cancers.

PMID- 21173380
TI  - Noise-induced hearing loss from MP3 players.

PMID- 21173381
TI  - Consent for biobanking: assessing the understanding and views of cancer patients.
AB  - Cancer patients were questioned about the consent process in a context in which
      they were routinely requested to donate tumor samples to research. After in-depth
      interviews of 19 patients, a 12-page questionnaire was designed and mailed to 745
      patients who had been recently treated for colorectal cancer, breast cancer, or a
      hematological malignancy at a French Regional Cancer Center at which an opt-in
      biobanking system has existed since 2002. The response rate was 77.0% (N = 574).
      Among responding patients, 349 (60.8%) of the 574 were in favor of a formal and
      signed consent. Concordance was low (kappa = 0.23) between the number of patients
      who declared in the survey that they had given consent (213 of 574 [37.1%]) vs
      the number for whom registered consent had been recorded (267 of 574 [46.5%]).
      Only 2 (0.3%) of the 574 patients stated that they had signed a refusal, and only
      88 (41.3%) of the 213 patients who remembered giving consent understood that
      their consent for biobanking also covered authorization to use their clinical
      data. We conclude that the opt-in consent procedure is positively perceived by
      most patients but should be improved for a better understanding and possibly an
      even better adherence to the consent process.

PMID- 21173379
TI  - Significance of circulating tumor cells in patients with squamous cell carcinoma
      of the head and neck: initial results.
AB  - OBJECTIVES: to present and discuss a high-performance negative depletion method
      for the isolation of circulating tumor cells (CTCs) in the blood of patients with
      head and neck cancer and to determine the correlation between the presence of
      CTCs and early clinical outcome in these patients. DESIGN: prospective clinical
      follow-up study of patients with squamous cell carcinoma of the head and neck
      (SCCHN) undergoing surgical intervention, who had peripheral blood examined for
      the presence of CTCs. PATIENTS: the study population comprised 48 patients
      diagnosed as having SCCHN and undergoing surgical intervention. INTERVENTION: a
      negative depletion process to isolate and quantify CTCs from the blood of
      patients with SCCHN using immunomagnetic separation was developed and validated.
      Immunostaining for cytokeratin was performed on the enriched samples to determine
      the number of CTCs extracted from each patient's blood sample. Correlation of the
      presence of CTCs, tumor stage, nodal status, clinical characteristics, and
      outcome was made. MAIN OUTCOME MEASURE: disease-free survival. RESULTS: our
      initial data, that have a mean follow-up of 19.0 months, suggest that patients
      with no detectable CTCs per milliliter of blood had a significantly higher
      probability of disease-free survival (P = .01). There was no correlation between
      the presence of CTCs with regard to age, sex, tumor site, stage, or nodal
      involvement. CONCLUSIONS: our enrichment technology, based on the removal of
      normal cells, has been used on the peripheral blood of patients with head and
      neck cancer for which follow-up data were collected. If no CTCs were present, a
      statistically significant improved disease-free survival was observed in SCCHN. A
      blood test with such a prognostic capability could have important implications in
      the treatment of patients with head and neck cancer.

PMID- 21173382
TI  - A novel epigenetic phenotype associated with the most aggressive pathway of
      bladder tumor progression.
AB  - BACKGROUND: Epigenetic silencing can extend to whole chromosomal regions in
      cancer. There have been few genome-wide studies exploring its involvement in
      tumorigenesis. METHODS: We searched for chromosomal regions affected by
      epigenetic silencing in cancer by using Affymetrix microarrays and real-time
      quantitative polymerase chain reaction to analyze RNA from 57 bladder tumors
      compared with normal urothelium. Epigenetic silencing was verified by gene re
      expression following treatment of bladder cell lines with 5-aza-deoxycytidine, a
      DNA demethylating agent, and trichostatin A, a histone deacetylase inhibitor. DNA
      methylation was studied by bisulfite sequencing and histone methylation and
      acetylation by chromatin immunoprecipitation. Clustering was used to distinguish
      tumors with multiple regional epigenetic silencing (MRES) from those without and
      to analyze the association of this phenotype with histopathologic and molecular
      types of bladder cancer. The results were confirmed with a second panel of 40
      tumor samples and extended in vitro with seven bladder cancer cell lines. All
      statistical tests were two-sided. RESULTS: We identified seven chromosomal
      regions of contiguous genes that were silenced by an epigenetic mechanism.
      Epigenetic silencing was not associated with DNA methylation but was associated
      with histone H3K9 and H3K27 methylation and histone H3K9 hypoacetylation. All
      seven regions were concordantly silenced in a subgroup of 26 tumors, defining an
      MRES phenotype. MRES tumors exhibited a carcinoma in situ-associated gene
      expression signature (25 of 26 MRES tumors vs 0 of 31 non-MRES tumors, P < 10
      14), rarely carried FGFR3 mutations (one of 26 vs 22 of 31 non-MRES tumors, P <
      10-16), and contained 25 of 33 (76%) of the muscle-invasive tumors. Cell lines
      derived from aggressive bladder tumors presented epigenetic silencing of the same
      regions. CONCLUSIONS: We have identified an MRES phenotype characterized by the
      concomitant epigenetic silencing of several chromosomal regions, which, in
      bladder cancer, is specifically associated with the carcinoma in situ gene
      expression signature.

PMID- 21173383
TI  - Proteomic profiling of a layered tissue reveals unique glycolytic specializations
      of photoreceptor cells.
AB  - The retina is a highly ordered tissue whose outermost layers are formed by
      subcellular compartments of photoreceptors generating light-evoked electrical
      responses. We studied protein distributions among individual photoreceptor
      compartments by separating the entire photoreceptor layer of a flat-mounted
      frozen retina into a series of thin tangential cryosections and analyzing protein
      compositions of each section by label-free quantitative mass spectrometry. Based
      on 5038 confidently identified peptides assigned to 896 protein database entries,
      we generated a quantitative proteomic database (a "map") correlating the
      distribution profiles of identified proteins with the profiles of marker proteins
      representing individual compartments of photoreceptors and adjacent cells. We
      evaluated the applicability of several common peptide-to-protein quantification
      algorithms in the context of our database and found that the highest reliability
      was obtained by summing the intensities of all peptides representing a given
      protein, using at least the 5-6 most intense peptides when applicable. We used
      this proteome map to investigate the distribution of glycolytic enzymes, critical
      in fulfilling the extremely high metabolic demands of photoreceptor cells, and
      obtained two major findings. First, unlike the majority of neurons rich in
      hexokinase I, but similar to other highly metabolically active cells,
      photoreceptors express hexokinase II. Hexokinase II has a very high catalytic
      activity when associated with mitochondria, and indeed we found it colocalized
      with mitochondria in photoreceptors. Second, photoreceptors contain very little
      triosephosphate isomerase, an enzyme converting dihydroxyacetone phosphate into
      glyceraldehyde-3-phosphate. This may serve as a functional adaptation because
      dihydroxyacetone phosphate is a major precursor in phospholipid biosynthesis, a
      process particularly active in photoreceptors because of the constant renewal of
      their light-sensitive membrane disc stacks. Overall, our approach for proteomic
      profiling of very small tissue amounts at a resolution of a few microns,
      combining cryosectioning and liquid chromatography-tandem MS, can be applied for
      quantitative investigation of proteomes where spatial resolution is paramount.

PMID- 21173385
TI  - Supervised home training of dialogue skills in chronic aphasia: a randomized
      parallel group study.
AB  - PURPOSE: The aim of this study was to prove the efficacy of supervised self
      training for individuals with aphasia. Linguistic and communicative performance
      in structured dialogues represented the main study parameters. METHOD: In a cross
      over design for randomized matched pairs, 18 individuals with chronic aphasia
      were examined during 12 weeks of supervised home training. Intensive language
      training, assisted by an electronic learning device (B.A.Bar), was compared with
      nonlinguistic training. Language performance, communicative abilities, and
      cognitive abilities were controlled before and after each intervention and at
      follow-up. The language training was designed to facilitate dialogue skills as
      required in everyday life. RESULTS: Robust and specific improvements in the
      participants' linguistic and communicative abilities were obtained using B.A.Bar
      dialogue training but not with nonlinguistic training. The transfer to general
      linguistic and communicative performance remained limited when the whole group
      was considered. For 30%-50% of the participants, individual analysis revealed
      significant improvements in spontaneous language and general communicative
      skills. Furthermore, individual participants demonstrated significant
      improvements regarding standardized aphasia assessment and proxy rating of
      communicative effectiveness. CONCLUSION: Supervised home training works. This
      study has proven that it is an effective tool for bolstering linguistic and
      communicative skills of individuals with aphasia.

PMID- 21173386
TI  - Quantitative study of vibrational symmetry of injured vocal folds via digital
      kymography in excised canine larynges.
AB  - PURPOSE: Digital kymography and vocal fold curve fitting are blended with
      detailed symmetry analysis of kymograms to provide a comprehensive
      characterization of the vibratory properties of injured vocal folds. METHOD:
      Vocal fold vibration of 12 excised canine larynges was recorded under uninjured,
      unilaterally injured, and bilaterally injured conditions. Kymograms were created
      at 25%, 50%, and 75% of the vocal fold length, and vibratory parameters were
      compared quantitatively among conditions and were studied with respect to right
      left and anterior-posterior symmetries. RESULTS: Anterior-posterior amplitude
      asymmetry was found in the bilateral condition. The unilateral condition showed
      significant right-left amplitude asymmetry, and it showed the lowest right-left
      phase symmetry among the conditions. In condition comparisons, vertical phase
      difference did not show significant differences among conditions, whereas
      amplitudes were significantly different among conditions at all line scan
      positions and most vocal fold lips. Significant differences in frequency were
      found among the conditions at all 4 vocal fold lips, with the bilateral condition
      exhibiting the greatest frequency. CONCLUSION: Digital kymography and curve
      fitting provide detailed information about the vibratory behavior of injured
      vocal folds. Awareness of vibratory properties associated with vocal fold injury
      may aid in diagnosis, and the quantitative abilities of digital kymography may
      allow for objective treatment selection.

PMID- 21173387
TI  - Development of a short form of the Boston naming test for individuals with
      aphasia.
AB  - PURPOSE: The purpose of this study was to develop a short form of the Boston
      Naming Test (BNT; Kaplan, Goodglass, & Weintraub, 2001) for individuals with
      aphasia and compare it with 2 existing short forms originally analyzed with
      responses from people with dementia and neurologically healthy adults. METHOD:
      Development of the new BNT-Aphasia Short Form and analysis of the other 2 forms
      were completed with archival data from 100 individuals with aphasia. The authors
      developed the BNT-Aphasia Short Form using items from the original 60-item
      instrument based on item response theory. Rasch analysis was computed on the
      short forms developed by Graves, Bezeau, Fogarty, and Blair (2004) and by Mack,
      Freed, Williams, and Henderson (1992). RESULTS: Analysis of the Graves et al.
      (2004) short form resulted in the smallest range of item difficulty and the
      largest floor effect compared with the Mack et al. (1992) short form and the BNT
      Aphasia short form. The BNT-Aphasia Short Form showed an increase in information
      in the middle of the scale relative to both the Graves et al. and the Mack et al.
      forms. CONCLUSIONS: The new short form demonstrates good psychometric properties
      when used with individuals with aphasia. However, the Mack et al. form proved to
      be as psychometrically sound as the BNT-Aphasia Short Form and is also
      appropriate for individuals with aphasia.

PMID- 21173388
TI  - Prosodic adaptations to pitch perturbation in running speech.
AB  - PURPOSE: A feedback perturbation paradigm was used to investigate whether
      prosodic cues are controlled independently or in an integrated fashion during
      sentence production. METHOD: Twenty-one healthy speakers of American English were
      asked to produce sentences with emphatic stress while receiving real-time
      auditory feedback of their productions. The fundamental frequency (F0) of the
      stressed word in each 4-word sentence was selectively shifted in a sensorimotor
      adaptation protocol. Speakers experienced either an upward or a downward shift of
      the stressed word, which gradually altered the perceived stress of the sentence.
      RESULTS: Participants in the Up and Down groups adapted to F0 shifts by altering
      the contrast between stressed and unstressed words differentially, such that the
      two groups deviated from each other in the perturbation phase. Furthermore,
      selective F0 perturbation in sentences with emphatic stress resulted in
      compensatory changes in both F0 and intensity. CONCLUSIONS: Present findings
      suggest that F0 and intensity are controlled in an integrated fashion to maintain
      the contrast between stressed and unstressed words. When a cue is impaired
      through perturbation, speakers not only oppose the perturbation but enhance other
      prosodic cues to achieve emphatic stress.

PMID- 21173389
TI  - Peer interactions of preschool children with and without hearing loss.
AB  - PURPOSE: Little is known about the social interaction skills of children with
      severe to profound hearing loss (SPHL) in terms of how they manage conversational
      exchanges with peers. This study compared the initiation and response skills of
      children with SPHL with those of children with typical hearing during group play
      in integrated preschool programs. METHOD: Two groups of 12 children were matched
      on a number of variables and assessed for intelligence, language, speech, and
      social development. All initiations, responses, and resulting interactions during
      20 min of group play were transcribed and coded. Outcome measures included number
      and type of initiation strategies, number of responses, and length of
      interactions. RESULTS: Despite poorer speech, language, and social development,
      there were no significant differences in initiation and response skills measured
      between children with SPHL and their matched peers. The small sample size may
      have made differences difficult to detect; however, playmates initiated
      interactions less often with the children with SPHL and ignored their initiations
      more often than those of other children. CONCLUSIONS: Preschool children with
      SPHL were excluded from interactions by their playmates. Having age-appropriate
      language skills did not ensure successful peer interactions. Inclusive preschool
      programs may consider offering classroom-wide social skills training to enhance
      interaction opportunities.

PMID- 21173384
TI  - Emerging roles for the transforming growth factor-{beta} superfamily in
      regulating adiposity and energy expenditure.
AB  - Members of the TGF-beta superfamily regulate many aspects of development,
      including adipogenesis. Studies in cells and animal models have characterized the
      effects of superfamily signaling on adipocyte development, adiposity, and energy
      expenditure. Although bone morphogenetic protein (BMP) 4 is generally considered
      a protein that promotes the differentiation of white adipocytes, BMP7 has emerged
      as a selective regulator of brown adipogenesis. Conversely, TGF-beta and activin
      A inhibit adipocyte development, a process augmented in TGF-beta-treated cells by
      Smads 6 and 7, negative regulators of canonical TGF-beta signaling. Other
      superfamily members have mixed effects on adipogenesis depending on cell culture
      conditions, the timing of expression, and the cell type, and many of these
      effects occur by altering the expression or activities of proteins that control
      the adipogenic cascade, including members of the CCAAT/enhancer binding protein
      family and peroxisome proliferator-activated receptor-gamma. BMP7, growth
      differentiation factor (GDF) 8, and GDF3 are versatile in their mechanisms of
      action, and altering their normal expression characteristics has significant
      effects on adiposity in vivo. In addition to their roles in adipogenesis,
      activins and BMP7 regulate energy expenditure by affecting the expression of
      genes that contribute to mitochondrial biogenesis and function. GDF8 signals
      through its own receptors during adipogenesis while antagonizing BMP7, an example
      of a ligand from one major branch of the superfamily regulating the other. With
      such intricate relationships that ultimately affect adiposity, TGF-beta
      superfamily signaling holds considerable promise as a target for treating human
      obesity and its comorbidities.

PMID- 21173390
TI  - Syllable-related breathing in infants in the second year of life.
AB  - PURPOSE: This study explored whether breathing behaviors of infants within the
      2nd year of life differ between tidal breathing and breathing supporting single
      unarticulated syllables and canonical/articulated syllables. METHOD:
      Vocalizations and breathing kinematics of 9 infants between 53 and 90 weeks of
      age were recorded. A strict selection protocol was used to identify analyzable
      breath cycles. Syllables were categorized on the basis of consensus coding.
      Inspiratory and expiratory durations, excursions, and slopes were calculated for
      the 3 breath cycle types and were normalized using mean tidal breath measures.
      RESULTS: Tidal breathing cycles were significantly different from syllable
      related cycles on all breathing measures. There were no significant differences
      between unarticulated syllable cycles and canonical syllable cycles, even after
      controlling for utterance duration and sound pressure level. CONCLUSIONS: Infants
      in the 2nd year of life exhibit clear differences between tidal breathing and
      speech-related breathing, but categorically distinct breath support for syllable
      types with varying articulatory demands was not evident in the present findings.
      Speech development introduces increasingly complex utterances, so older infants
      may produce detectable articulation-related adaptations of breathing kinematics.
      For younger infants, breath support may vary systematically among utterance
      types, due more to phonatory variations than to articulatory demands.

PMID- 21173391
TI  - Changes in acoustic characteristics of the voice across the life span: measures
      from individuals 4-93 years of age.
AB  - PURPOSE: The purpose of the present investigation was to examine acoustic voice
      changes across the life span. Previous voice production investigations used small
      numbers of participants, had limited age ranges, and produced contradictory
      results. METHOD: Voice recordings were made from 192 male and female participants
      4-93 years of age. Acoustic measures of fundamental frequency (F0), sound
      pressure level (SPL), and signal-to-noise ratio (SNR) were made. Coefficients of
      variation for F0, SPL, and SNR served as measures of variability. Variables were
      analyzed separately with stepwise regressions, using age and sex as predictors.
      RESULTS: Differences in F0 and SNR across the life span were sex specific. Male
      and female participants demonstrated significant nonlinear trends for F0, but the
      trends were stronger for male participants. Female participants demonstrated a
      similar nonlinear trend for SNR, whereas male participants demonstrated linear
      increases in SNR with age. Variability of F0, SPL, and SNR followed nonlinear
      trends, higher at younger and older ages. CONCLUSIONS: Changes in voice
      production occur throughout the life span, often in a nonlinear way and
      differently for male and female individuals. Higher variability of acoustic
      measures of voice in both young and old speakers reflects changes in anatomic
      structure, physiologic mechanisms, and motor control.

PMID- 21173392
TI  - Perceptual adaptation of voice gender discrimination with spectrally shifted
      vowels.
AB  - PURPOSE: To determine whether perceptual adaptation improves voice gender
      discrimination of spectrally shifted vowels and, if so, which acoustic cues
      contribute to the improvement. METHOD: Voice gender discrimination was measured
      for 10 normal-hearing subjects, during 5 days of adaptation to spectrally shifted
      vowels, produced by processing the speech of 5 male and 5 female talkers with 16
      channel sine-wave vocoders. The subjects were randomly divided into 2 groups; one
      subjected to 50-Hz, and the other to 200-Hz, temporal envelope cutoff
      frequencies. No preview or feedback was provided. RESULTS: There was significant
      adaptation in voice gender discrimination with the 200-Hz cutoff frequency, but
      significant improvement was observed only for 3 female talkers with F(0) > 180 Hz
      and 3 male talkers with F(0) < 170 Hz. There was no significant adaptation with
      the 50-Hz cutoff frequency. CONCLUSIONS: Temporal envelope cues are important for
      voice gender discrimination under spectral shift conditions with perceptual
      adaptation, but spectral shift may limit the exclusive use of spectral
      information and/or the use of formant structure on voice gender discrimination.
      The results have implications for cochlear implant users and for understanding
      voice gender discrimination.

PMID- 21173393
TI  - Treatment of category generation and retrieval in aphasia: effect of typicality
      of category items.
AB  - PURPOSE: Kiran and colleagues (Kiran, 2007, 2008; Kiran & Johnson, 2008; Kiran &
      Thompson, 2003) previously suggested that training atypical examples within a
      semantic category is a more efficient treatment approach to facilitating
      generalization within the category than training typical examples. In the present
      study, the authors extended previous work examining the notion of semantic
      complexity within goal-derived (ad hoc) categories in individuals with aphasia.
      Methods Six individuals with fluent aphasia (age range = 39-84 years) and varying
      degrees of naming deficits and semantic impairments were involved. Thirty typical
      and atypical items, each from 2 categories, were selected after an extensive
      stimulus norming task. Generative naming for the 2 categories was tested during
      baseline and treatment. RESULTS: As predicted, training atypical examples in the
      category resulted in generalization to untrained typical examples in 5 of 5
      patient-treatment conditions. In contrast, training typical examples (which was
      examined in 3 conditions) produced mixed results. One patient showed
      generalization to untrained atypical examples, whereas 2 patients did not show
      generalization to untrained atypical examples. CONCLUSION: Results of the present
      study supplement existing data on the effect of a semantically based treatment
      for lexical retrieval by manipulating the typicality of category examples.

PMID- 21173395
TI  - Clinical and research perspectives on nonspeech oral motor treatments and
      evidence-based practice.
AB  - PURPOSE: Evidence-based practice (EBP) involves the incorporation of research
      evidence, clinical expertise, and client values in clinical decision making. One
      case in which these factors conflict is the use of nonspeech oral motor
      treatments (NSOMTs) for children with developmental speech sound disorders.
      Critical reviews of the research evidence suggest that NSOMTs are not valid, yet
      they are widely used by clinicians based on their expertise/experience. This
      investigation presents detailed descriptions of clinicians' and researchers'
      views and opinions on NSOMTs and EBP. METHOD: Individual interviews with 11
      clinicians who use NSOMTs and 11 researchers in child phonology were conducted.
      The interviews were transcribed and organized into themes, following a
      phenomenological research design. RESULTS: Five themes were identified: (a)
      NSOMTs are effective, (b) EBP is useful, (c) there is no published research
      supporting NSOMTs, (d) research evidence may change clinical use of NSOMTs, and
      (e) researchers and clinicians have separate but shared roles in clinical
      decision making. CONCLUSIONS: The participants' responses provided detailed and
      complex insights into each group's decisions regarding NSOMTs. These responses
      also suggested questions that should be considered when making decisions about
      approaches that are not fully supported by EBP.

PMID- 21173394
TI  - Working memory training for children with cochlear implants: a pilot study.
AB  - PURPOSE: This study investigated the feasibility and efficacy of a working memory
      training program for improving memory and language skills in a sample of 9
      children who are deaf (age 7-15 years) with cochlear implants (CIs). METHOD: All
      children completed the Cogmed Working Memory Training program on a home computer
      over a 5-week period. Feasibility and acceptability of the program were evaluated
      using parent report and measures of children's performance on the training
      exercises. Efficacy measures of working memory and sentence repetition were
      obtained prior to training, immediately after training, and 1 month and 6 months
      after training. RESULTS: Children's performance improved on most training
      exercises, and parents reported no problems with children's hearing or
      understanding of the exercises. After completion of working memory training,
      children demonstrated significant improvement on measures of verbal and nonverbal
      working memory, parent-reported working memory behavior, and sentence-repetition
      skills. The magnitude of improvement in working memory decreased slightly at the
      1-month follow-up and more substantially at 6-month follow-up. However, sentence
      repetition continued to show marked improvement at 6-month follow-up.
      CONCLUSIONS: Working memory training may produce benefit for some memory and
      language skills for children with CIs, supporting the importance of conducting a
      large-scale, randomized clinical trial with this population.

PMID- 21173396
TI  - Assessment and treatment of working memory deficits in school-age children: the
      role of the speech-language pathologist.
AB  - PURPOSE: To review research addressing the relationship of working memory (WM) to
      language development and academic functioning and to consider the role of the
      speech-language pathologist (SLP) in assessment and intervention of WM
      difficulties in school-age children. METHOD: Aspects of WM critical to language
      acquisition and academic success are defined, and the importance of WM to
      language development and learning is discussed. Subsequently, strategies for
      assessing WM skills in children are presented. Following a discussion regarding
      the assessment of WM demands in the classroom, intervention strategies are
      provided. RESULTS: Children with poor WM skills are likely to experience
      significant difficulty in academic settings. Evidence-based strategies for both
      reducing WM demands and improving functional WM skills are reviewed. CONCLUSION:
      Research to date has documented that children with language impairments
      frequently have poor WM skills. SLPs can support poor WM skills by considering
      both modifications to the environment and child-enacted knowledge and skills,
      which may serve to reduce the impact of poor WM skills on learning and academic
      success.

PMID- 21173397
TI  - Summaries for patients. Echinacea for the common cold.

PMID- 21173398
TI  - Summaries for patients. Dietary trans-palmitoleic acid and diabetes.

PMID- 21173399
TI  - ACP Journal Club. Review: Steroids, US, electromagnetic field therapy, and
      nocturnal splinting have moderate, short-term effectiveness for the carpal tunnel
      syndrome.

PMID- 21173400
TI  - ACP Journal Club. In older patients, rosiglitazone was associated with increased
      risk for stroke, heart failure, and mortality compared with pioglitazone.

PMID- 21173401
TI  - ACP Journal Club. Use of bisphosphonates was not associated with increased risk
      for esophageal or gastric cancer.

PMID- 21173402
TI  - ACP Journal Club. Adding clopidogrel to proton-pump inhibitors was not associated
      with increased CV risk after MI.

PMID- 21173403
TI  - ACP Journal Club. A promotional, educational intervention increased staff
      influenza vaccination in primary care.

PMID- 21173404
TI  - ACP Journal Club. Early palliative care improved quality of life in patients with
      newly diagnosed metastatic NSCLC.

PMID- 21173405
TI  - ACP Journal Club. A biobehavioral intervention improved caregiver well-being and
      some measures of functioning in patients with dementia.

PMID- 21173406
TI  - ACP Journal Club. Review: Polyethylene glycol is more effective than lactulose
      for chronic constipation in children and adults.

PMID- 21173407
TI  - ACP Journal Club. Review: Graduated compression stockings reduce deep venous
      thrombosis in hospitalized patients.

PMID- 21173408
TI  - ACP Journal Club. Testosterone increased risk for adverse events in older men
      with mobility limitations.

PMID- 21173409
TI  - ACP Journal Club. Review: Angiotensin-receptor blockers increase risk for cancer
      but not cancer-related death.

PMID- 21173410
TI  - ACP Journal Club. Population-based screening using prostate-specific antigen
      testing reduced prostate cancer mortality.

PMID- 21173411
TI  - Echinacea for treating the common cold: a randomized trial.
AB  - BACKGROUND: Echinacea is widely used to treat the common cold. OBJECTIVE: To
      assess the potential benefits of echinacea as a treatment of common cold. DESIGN:
      Randomized, controlled trial. (ClinicalTrials.gov registration number:
      NCT00065715) SETTING: Dane County, Wisconsin. PATIENTS: 719 patients, aged 12 to
      80 years, with new-onset common cold. INTERVENTION: Patients were assigned to 1
      of 4 parallel groups: no pills, placebo pills (blinded), echinacea pills
      (blinded), or echinacea pills (unblinded, open-label). Echinacea groups received
      the equivalent of 10.2 g of dried echinacea root during the first 24 hours and
      5.1 g during each of the next 4 days. Indistinguishable placebo tablets contained
      only inert ingredients. MEASUREMENTS: The primary outcome was the area under the
      curve for global severity, with severity assessed twice daily by self-report
      using the Wisconsin Upper Respiratory Symptom Survey, short version. Secondary
      outcomes included interleukin-8 levels and neutrophil counts from nasal wash,
      assessed at intake and 2 days later. RESULTS: Of the 719 patients enrolled, 713
      completed the protocol. Mean age was 33.7 years, 64% were female, and 88% were
      white. Mean global severity was 236 and 258 for the blinded and unblinded
      echinacea groups, respectively; 264 for the blinded placebo group; and 286 for
      the no-pill group. A comparison of the 2 blinded groups showed a 28-point trend
      (95% CI, -69 to 13 points) toward benefit for echinacea (P = 0.089). Mean illness
      duration in the blinded and unblinded echinacea groups was 6.34 and 6.76 days,
      respectively, compared with 6.87 days in the blinded placebo group and 7.03 days
      in the no-pill group. A comparison of the blinded groups showed a nonsignificant
      0.53-day (CI, -1.25 to 0.19 days) benefit (P = 0.075). Median change in
      interleukin-8 levels and neutrophil counts were also not statistically
      significant (30 ng/L and 1 cell/high-power field [hpf] in the no-pill group, 39
      ng/L and 1 cell/hpf in the blinded placebo group, 58 ng/L and 2 cells/hpf in the
      blinded echinacea group, and 70 ng/L and 1 cell/hpf in the open-label echinacea
      group). LIMITATION: Higher-than-expected variability limited power to detect
      small benefits. CONCLUSION: Illness duration and severity were not statistically
      significant with echinacea compared with placebo. These results do not support
      the ability of this dose of the echinacea formulation to substantively change the
      course of the common cold. PRIMARY FUNDING SOURCE: National Center for
      Complementary and Alternative Medicine, National Institutes of Health.

PMID- 21173412
TI  - The cost-effectiveness and population outcomes of expanded HIV screening and
      antiretroviral treatment in the United States.
AB  - BACKGROUND: Although recent guidelines call for expanded routine screening for
      HIV, resources for antiretroviral therapy (ART) are limited, and all eligible
      persons are not currently receiving treatment. OBJECTIVE: To evaluate the effects
      on the U.S. HIV epidemic of expanded ART, HIV screening, or interventions to
      reduce risk behavior. DESIGN: Dynamic mathematical model of HIV transmission and
      disease progression and cost-effectiveness analysis. DATA SOURCES: Published
      literature. TARGET POPULATION: High-risk (injection drug users and men who have
      sex with men) and low-risk persons aged 15 to 64 years in the United States. TIME
      HORIZON: Twenty years and lifetime (costs and quality-adjusted life-years
      [QALYs]). PERSPECTIVE: Societal. INTERVENTION: Expanded HIV screening and
      counseling, treatment with ART, or both. OUTCOME MEASURES: New HIV infections,
      discounted costs and QALYs, and incremental cost-effectiveness ratios. RESULTS OF
      BASE-CASE ANALYSIS: One-time HIV screening of low-risk persons coupled with
      annual screening of high-risk persons could prevent 6.7% of a projected 1.23
      million new infections and cost $22,382 per QALY gained, assuming a 20% reduction
      in sexual activity after screening. Expanding ART utilization to 75% of eligible
      persons prevents 10.3% of infections and costs $20,300 per QALY gained. A
      combination strategy prevents 17.3% of infections and costs $21,580 per QALY
      gained. RESULTS OF SENSITIVITY ANALYSIS: With no reduction in sexual activity,
      expanded screening prevents 3.7% of infections. Earlier ART initiation when a CD4
      count is greater than 0.350 * 10(9) cells/L prevents 20% to 28% of infections.
      Additional efforts to halve high-risk behavior could reduce infections by 65%.
      LIMITATION: The model of disease progression and treatment was simplified, and
      acute HIV screening was excluded. CONCLUSION: Expanding HIV screening and
      treatment simultaneously offers the greatest health benefit and is cost
      effective. However, even substantial expansion of HIV screening and treatment
      programs is not sufficient to markedly reduce the U.S. HIV epidemic without
      substantial reductions in risk behavior. PRIMARY FUNDING SOURCE: National
      Institute on Drug Abuse, National Institutes of Health, and Department of
      Veterans Affairs.

PMID- 21173413
TI  - Trans-palmitoleic acid, metabolic risk factors, and new-onset diabetes in U.S.
      adults: a cohort study.
AB  - BACKGROUND: Palmitoleic acid (cis-16:1n-7), which is produced by endogenous fat
      synthesis, has been linked to both beneficial and deleterious metabolic effects,
      potentially confounded by diverse determinants and tissue sources of endogenous
      production. Trans-palmitoleate (trans-16:1n-7) represents a distinctly exogenous
      source of 16:1n-7, unconfounded by endogenous synthesis or its determinants, that
      may be uniquely informative. OBJECTIVE: To investigate whether circulating trans
      palmitoleate is independently related to lower metabolic risk and incident type 2
      diabetes. DESIGN: Prospective cohort study from 1992 to 2006. SETTING: Four U.S.
      communities. PATIENTS: 3736 adults in the Cardiovascular Health Study.
      MEASUREMENTS: Anthropometric characteristics and levels of plasma phospholipid
      fatty acids, blood lipids, inflammatory markers, and glucose-insulin measured at
      baseline in 1992 and dietary habits measured 3 years earlier. Multivariate
      adjusted models were used to investigate how demographic, clinical, and lifestyle
      factors independently related to plasma phospholipid trans-palmitoleate; how
      trans-palmitoleate related to major metabolic risk factors; and how trans
      palmitoleate related to new-onset diabetes (304 incident cases). Findings were
      validated for metabolic risk factors in an independent cohort of 327 women.
      RESULTS: In multivariate analyses, whole-fat dairy consumption was most strongly
      associated with higher trans-palmitoleate levels. Higher trans-palmitoleate
      levels were associated with slightly lower adiposity and, independently, with
      higher high-density lipoprotein cholesterol levels (1.9% across quintiles; P =
      0.040), lower triglyceride levels (-19.0%; P < 0.001), a lower total cholesterol
      HDL cholesterol ratio (-4.7%; P < 0.001), lower C-reactive protein levels (
      13.8%; P = 0.05), and lower insulin resistance (-16.7%, P < 0.001). Trans
      palmitoleate was also associated with a substantially lower incidence of
      diabetes, with multivariate hazard ratios of 0.41 (95% CI, 0.27 to 0.64) and 0.38
      (CI, 0.24 to 0.62) in quintiles 4 and 5 versus quintile 1 (P for trend < 0.001).
      Findings were independent of estimated dairy consumption or other fatty acid
      dairy biomarkers. Protective associations with metabolic risk factors were
      confirmed in the validation cohort. LIMITATION: Results could be affected by
      measurement error or residual confounding. CONCLUSION: Circulating trans
      palmitoleate is associated with lower insulin resistance, presence of atherogenic
      dyslipidemia, and incident diabetes. Our findings may explain previously observed
      metabolic benefits of dairy consumption and support the need for detailed further
      experimental and clinical investigation. PRIMARY FUNDING SOURCE: National Heart,
      Lung, and Blood Institute and National Institute of Diabetes and Digestive and
      Kidney Diseases of the National Institutes of Health.

PMID- 21173414
TI  - Meta-analysis: statin therapy does not alter the association between low levels
      of high-density lipoprotein cholesterol and increased cardiovascular risk.
AB  - BACKGROUND: Low levels of high-density lipoprotein cholesterol (HDL-C) are
      associated with an increased risk for myocardial infarction (MI). Although
      statins reduce the risk for MI, most cardiovascular events still occur despite
      statin treatment. PURPOSE: Using meta-analysis of large randomized, controlled
      trials (RCTs) of statins to determine whether statins alter the relationship
      between HDL-C level and MI. DATA SOURCES: MEDLINE search to February 2010,
      ClinicalTrials.gov, and reference lists from eligible studies. STUDY SELECTION:
      English-language RCTs of statin-treated patients versus control participants with
      1000 or more person-years of follow-up and reported HDL-C levels and MI. DATA
      EXTRACTION: Two independent investigators extracted data from eligible RCTs. DATA
      SYNTHESIS: Twenty eligible RCTs were identified (543,210 person-years of follow
      up and 7838 MIs). After adjustment for on-treatment LDL-C levels, age,
      hypertension, diabetes, and tobacco use, there was a significant inverse
      association between HDL-C levels and risk for MI in statin-treated patients and
      control participants. In Poisson meta-regressions, every 0.26-mmol/L (10-mg/dL)
      decrease in HDL-C was associated with 7.1 (95% CI, 6.8 to 7.3) and 8.3 (CI, 8.1
      to 8.5) more MIs per 1000 person-years in statin-treated patients and control
      participants, respectively. The inverse association between HDL-C levels and MI
      did not differ between statin-treated patients and control participants (P=
      0.57). LIMITATION: The observed associations may be explained by unmeasured
      confounding and do not imply causality in the relationship between HDL-C level
      and cardiovascular risk. CONCLUSION: Statins do not alter the relationship
      between HDL-C level and cardiovascular risk, such that low levels of HDL-C remain
      significantly and independently associated with increased risk despite statin
      treatment. The remaining risk seen in statin-treated patients may be partly
      explained by low HDL-C levels or other factors associated with low levels of HDL
      C. PRIMARY FUNDING SOURCE: None.

PMID- 21173415
TI  - Reconsidering the approach to prevention recommendations for older adults.
AB  - The U.S. Preventive Services Task Force (USPSTF) bases its recommendations on an
      evidence-based model of clinical prevention that focuses on specific diseases,
      well-defined preventive interventions, and evidence of improved health outcomes.
      Applying this model to prevention for very old patients has been problematic for
      several reasons: Many geriatric disorders have multiple risk factors,
      interventions, and expected outcomes; older adults are not often represented in
      clinical trials; and important outcomes may not be measured and reported in ways
      that are conducive to evidence synthesis and interpretation. In 2005, the USPSTF
      convened a geriatrics workgroup to refine USPSTF methodology and processes to
      better address the preventive needs of older adults. The USPSTF has begun to
      apply these new approaches to the review and recommendation on interventions to
      prevent falls in older adults.

PMID- 21173416
TI  - Primary care-relevant interventions to prevent falling in older adults: a
      systematic evidence review for the U.S. Preventive Services Task Force.
AB  - BACKGROUND: Falls among older adults are both prevalent and preventable. PURPOSE:
      To describe the benefits and harms of interventions that could be used by primary
      care practitioners to prevent falling among community-dwelling older adults. DATA
      SOURCES: The reviewers evaluated trials from a good-quality systematic review
      published in 2003 and searched MEDLINE, the Cochrane Central Register of
      Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL from the
      end of that review's search date to February 2010 to identify additional English
      language trials. STUDY SELECTION: Two reviewers independently screened 3423
      abstracts and 638 articles to identify randomized, controlled trials (RCTs) of
      primary care-relevant interventions among community-dwelling older adults that
      reported falls or fallers as an outcome. Trials were independently critically
      appraised to include only good- or fair-quality trials; discrepancies were
      resolved by a third reviewer. DATA EXTRACTION: One reviewer abstracted data from
      61 articles into standardized evidence tables that were verified by a second
      reviewer. DATA SYNTHESIS: Overall, the included evidence was of fair quality. In
      16 RCTs evaluating exercise or physical therapy, interventions reduced falling
      (risk ratio, 0.87 [95% CI, 0.81 to 0.94]). In 9 RCTs of vitamin D
      supplementation, interventions reduced falling (risk ratio, 0.83 [CI, 0.77 to
      0.89]). In 19 trials involving multifactorial assessment and management,
      interventions with comprehensive management seemed to reduce falling, although
      overall pooled estimates were not statistically significant (risk ratio, 0.94
      [CI, 0.87 to 1.02]). Limited evidence suggested that serious clinical harms were
      no more common for older adults in intervention groups than for those in control
      groups. LIMITATIONS: Interventions and methods of fall ascertainment were
      heterogeneous. Data on potential harms of interventions were scant and often not
      reported. CONCLUSION: Primary care-relevant interventions exist that can reduce
      falling among community-dwelling older adults. PRIMARY FUNDING SOURCE: Agency for
      Healthcare Research and Quality.

PMID- 21173417
TI  - Systematic review: association of shift length, protected sleep time, and night
      float with patient care, residents' health, and education.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education's new duty
      hour standards limit interns' shifts to 16 hours and night float to 6 consecutive
      nights. Protected sleep time (that is, "nap") is strongly encouraged. As duty
      hour reforms are implemented, examination of the quality and outcomes of the
      relevant literature is important. PURPOSE: To systematically review the
      literature examining shift length, protected sleep time, and night float. DATA
      SOURCES: MEDLINE, PREMEDLINE, and EMBASE from January 1989 through May 2010.
      STUDY SELECTION: Studies examined the associations of shift length, protected
      sleep time, or night float with patient care, resident health, and education
      outcomes among residents in practice settings. DATA EXTRACTION: Study quality was
      measured by using the validated Medical Education Research Study Quality
      Instrument and the U.S. Preventive Services Task Force criteria. Two
      investigators independently rated study quality, and interrater agreement was
      calculated. DATA SYNTHESIS: Sixty-four studies met inclusion criteria. Most
      studies used single-group cross-sectional (19 studies [29.7%]) or pre-post (41
      studies [64.1%]) designs, and 4 (6.3%) were randomized, controlled trials. Five
      studies (7.8%) were multi-institutional. Twenty-four of 33 (72.7%) studies
      examining shift length reported that shorter shifts were associated with
      decreased medical errors, motor vehicle crashes, and percutaneous injuries. Only
      2 studies assessed protected sleep time and reported that residents' adherence to
      naps was poor. Night floats described in 33 studies involved 5 to 7 consecutive
      nights. LIMITATIONS: Most studies used single-institution, observational designs.
      Publication bias is likely but difficult to assess in this methodologically weak
      and heterogeneous body of evidence. CONCLUSION: For the limited outcomes
      measured, most studies supported reducing shift length but did not adequately
      address the optimal shift duration. Studies had numerous methodological
      limitations and unclear generalizability for most outcomes. Specific
      recommendations about shift length, protected sleep time, and night float should
      acknowledge the limitations of this evidence. PRIMARY FUNDING SOURCE:
      Accreditation Council for Graduate Medical Education.

PMID- 21173418
TI  - Making prevention recommendations relevant for an aging population.

PMID- 21173419
TI  - Does the relationship between hemoglobin A1c and mean glucose levels differ by
      race?

PMID- 21173420
TI  - A Brugada-pattern electrocardiogram and thyrotoxic periodic paralysis.

PMID- 21173421
TI  - A Brugada-pattern electrocardiogram and adrenal insufficiency.

PMID- 21173422
TI  - The breastfeeding team: the role of involved fathers in the breastfeeding family.
AB  - Fathers influence mothers' breastfeeding decisions and experiences. Fathers'
      perceptions of their roles as members of the breastfeeding family are likely
      important components of that influence. To explore that possibility, 21 involved
      fathers of breastfeeding babies volunteered to be interviewed regarding their
      fathering breastfed babies and their roles in the breastfeeding family. Fathers
      identified their unique roles as team members ensuring that their babies received
      the benefits of breastfeeding. A primary fathering role was that of supporting
      breastfeeding by becoming breastfeeding savvy, by using their knowledge to
      encourage and assist mothers in breastfeeding, by valuing the breastfeeding
      mothers, and by sharing housework and child care. Fathers' nurturing roles
      involved fostering positive father-infant relationships in the face of limited
      opportunities to bond with their babies through feeding. The experiences of these
      fathers suggest the importance of assisting them to recognize their unique
      contributions to the nurture of their children as members of the breastfeeding
      team.

PMID- 21173423
TI  - "They've walked in my shoes": mothers of very low birth weight infants and their
      experiences with breastfeeding peer counselors in the neonatal intensive care
      unit.
AB  - The effectiveness of the breastfeeding peer counselor role is thought to be
      embedded in the relationship between new and experienced mothers. In this study,
      new mothers of very low birth weight infants emphasized that one of the most
      important aspects of their relationship with the breastfeeding peer counselors is
      the peer or shared experience of how difficult it can be to provide milk and
      breastfeed while coping with the emotional stress of having an infant in the
      neonatal intensive care unit. This study provides evidence for the promotion and
      facilitation of lactation for mothers of neonatal intensive care unit infants
      through the use of breastfeeding peer counselors who are peers by virtue of the
      shared experience of providing milk for an infant hospitalized in the neonatal
      intensive care unit.

PMID- 21173425
TI  - The child's experience of ADHD.
AB  - OBJECTIVE: This study aimed to investigate the agreement between parent- and
      child-reported quality of life (QoL) and the self-perceptions of children with
      ADHD. METHOD: A cross-sectional survey of school-aged children with ADHD and
      their parents was undertaken. RESULTS: Parents reported their child's QoL as
      lower than the children rated themselves in most QoL domains. Children reporting
      higher QoL than their parents had higher self-worth, than children who reported
      lower QoL. There was no difference in ADHD or oppositional symptoms or child age
      for children reporting higher versus lower QoL than their parents. Children
      reported experiencing ADHD symptoms and positive aspects in taking stimulant
      medication. CONCLUSION: It is important to elicit the report of both parents and
      children for understanding the functional impairment of children with ADHD.
      Children who report lower child QoL than their parents have lower overall self
      worth; these children may be at risk for developing internalizing difficulties.

PMID- 21173424
TI  - Effective population size and the efficacy of selection on the X chromosomes of
      two closely related Drosophila species.
AB  - The prevalence of natural selection relative to genetic drift is of central
      interest in evolutionary biology. Depending on the distribution of fitness
      effects of new mutations, the importance of these evolutionary forces may differ
      in species with different effective population sizes. Here, we survey population
      genetic variation at 105 orthologous X-linked protein coding regions in
      Drosophila melanogaster and its sister species D. simulans, two closely related
      species with distinct demographic histories. We observe significantly higher
      levels of polymorphism and evidence for stronger selection on codon usage bias in
      D. simulans, consistent with a larger historical effective population size on
      average for this species. Despite these differences, we estimate that <10% of
      newly arising nonsynonymous mutations have deleterious fitness effects in the
      nearly neutral range (i.e., -10 < N(e)s < 0) in both species. The inferred
      distributions of fitness effects and demographic models translate into
      surprisingly high estimates of the fraction of "adaptive" protein divergence in
      both species (~ 85-90%). Despite evidence for different demographic histories,
      differences in population size have apparently played little role in the dynamics
      of protein evolution in these two species, and estimates of the adaptive fraction
      (alpha) of protein divergence in both species remain high even if we account for
      recent 10-fold growth. Furthermore, although several recent studies have noted
      strong signatures of recurrent adaptive protein evolution at genes involved in
      immunity, reproduction, sexual conflict, and intragenomic conflict, our finding
      of high levels of adaptive protein divergence at randomly chosen proteins (with
      respect to function) suggests that many other factors likely contribute to the
      adaptive protein divergence signature in Drosophila.

PMID- 21173426
TI  - Clinically relevant changes in emotional expression in children with ADHD treated
      with lisdexamfetamine dimesylate.
AB  - OBJECTIVE: To describe clinically relevant effects of lisdexamfetamine dimesylate
      (LDX) on emotional expression (EE) in children with ADHD. METHOD: Children with
      ADHD participated in a 7-week, open-label, LDX dose-optimization study.
      Expression and Emotion Scale for Children (EESC) change scores were analyzed post
      hoc using two methods to determine proportion of participants with different
      categories of clinical response based on (a) clinically significant (movement >2
      SD from baseline mean)/reliable change (not due to measurement error) and (b)
      standard error of measurement (SEM) as a measure of clinically meaningful change.
      RESULTS: With LDX, no participants showed clinically significant/reliable
      improvement; 0.7% showed clinically significant/reliable deterioration of EE by
      reliable change index and movement from baseline mean. One third of participants
      had improved EE by SEM criteria; 9.2% had categorical worsening. CONCLUSION:
      Using clinically meaningful change and clinically significant/reliable change
      categories derived from the EESC, most participants had no worsening of EE with
      LDX.

PMID- 21173427
TI  - Symptoms of ADHD and close friendships in adolescence.
AB  - OBJECTIVE: This study examined the relationship of ADHD symptoms to different
      aspects of close friendship quality as rated by both adolescents (target
      adolescent and a close friend) within a friendship dyad. METHOD: Participants
      were 41 same-sex friendship dyads who completed questionnaires about their
      friendship. Separate symptom dimensions of ADHD (inattention and hyperactivity
      impulsivity) were examined. Teacher and parent ratings of social functioning were
      also used. RESULTS: Symptoms of inattention, hyperactivity-impulsivity, and
      overall ADHD were positively related to target-reported friendship quality, and
      symptoms of inattention and total ADHD were positively associated with friend
      reported friendship quality. Potential explanations for these surprising findings
      were explored. CONCLUSION: Results suggest that the close friendships of
      adolescents with symptoms of ADHD may be distinct from the peer rejection
      commonly faced by this population and that adolescents with symptoms of ADHD may
      have at least one close, positive friendship. Treatment implications and future
      research directions are discussed.

PMID- 21173428
TI  - Sex differences in the manifestation of ADHD in emerging adults.
AB  - OBJECTIVE: Given the mixed literature in the area, the aim of the current study
      was to determine whether sex differences exist in inattention, hyperactivity, and
      impairment in college adults with ADHD. METHOD: Individuals from three
      universities were recruited for the study. Participants with (n = 164) and
      without ADHD (n = 710) completed on-line measures of symptoms and impairment.
      RESULTS: College women with ADHD were shown to have higher rates of inattention,
      hyperactivity, and impairment than college women without ADHD and college men
      with ADHD. Analyses revealed that women in college who have ADHD experience
      higher levels of impairment in the following domains: home life, social life,
      education, money management, and daily life activities. CONCLUSION: Overall,
      clear differences emerged between men and women with ADHD. Implications and
      future directions are discussed.

PMID- 21173429
TI  - Association of parental ADHD and depression with externalizing and internalizing
      dimensions of child psychopathology.
AB  - OBJECTIVE: To study the independent association of parental depression and ADHD
      on three dimensions of child psychopathology among 178 children aged 5 to 10
      years. METHOD: Self-reported measures of parental depression and ADHD as well as
      rating scales and structure diagnostic interviews of child internalizing, ADHD,
      and externalizing problems were obtained. RESULTS: Structural equation modeling
      indicated that parental ADHD was positively associated with a broad child
      problems factor after a second-order factor of child problems best accounted for
      the high intercorrelations among the internalizing, ADHD, and externalizing child
      psychopathology factors. Parental depression did not significantly predict the
      second-order child problems factor, but it specifically predicted the child
      internalizing factor. CONCLUSION: These results suggest that parental ADHD may be
      a nonspecific risk factor for child psychopathology broadly, whereas parental
      depression may function as a specific risk factor for child internalizing
      problems.

PMID- 21173430
TI  - Comorbidity of migraine with ADHD.
AB  - OBJECTIVE: The purpose of this study was to investigate how often drugs used to
      treat migraine and ADHD are prescribed to the same patients to assess,
      indirectly, the comorbidity of these disorders. METHOD: We used data from the
      Norwegian prescription database for 2006, including the total Norwegian
      population (N = 4,640,219). RESULTS: Antimigraine drugs were prescribed to 81,225
      persons (1.75% of the total population), anti-ADHD drugs to 18,481 persons
      (0.40%), and 284 persons were prescribed both types of drugs. There was a
      positive and significant association between prescription of antimigraine and
      anti-ADHD drugs for all age groups between 20 and 50 for both genders, with odds
      ratios ranging from 1.76 to 2.81. CONCLUSION: The prescription patterns for these
      drugs in adult patients indicate a comorbidity between migraine and ADHD.

PMID- 21173431
TI  - Constitutive active/androstane receptor promotes hepatocarcinogenesis in a mouse
      model of non-alcoholic steatohepatitis.
AB  - The nuclear receptor constitutive active/androstane receptor (CAR) acts as a
      sensor of toxic byproducts derived from the endogenous metabolism and exogenous
      chemicals. We previously reported that CAR is responsible for exacerbating
      hepatic injury and fibrosis in a dietary model of non-alcoholic steatohepatitis
      (NASH) via upregulation of lipid peroxidation. In this study, we investigated the
      pathological roles of the CAR in the development of hepatocellular carcinoma in
      NASH model. CAR+/+ and CAR-/- mice were fed methionine- and choline-deficient
      (MCD) diet after tumor initiation with a single dose of the genotoxic carcinogen
      diethylnitrosamine (DEN) at 2 weeks of age. Interestingly, the MCD diet
      dramatically promoted DEN-induced hepatocarcinogenesis in CAR+/+ mice. However,
      the deletion of CAR leads to a significantly lower tumor incidence and smaller
      tumor diameter. Hepatocytes of MCD-treated-CAR+/+ mice showed a significantly
      higher staining frequency of Ki-67, a marker of cell proliferation, and exhibited
      a higher expression of c-Myc and FoxM1 transcripts compared with MCD-treated CAR
      /- mice. Immunohistochemistry revealed the nuclear translocation of CAR thus
      suggesting that the activation of CAR signaling increased in the hepatocytes of
      CAR+/+ mice fed MCD diet. In addition, in vitro experiments using the CAR stably
      expressed cell line with TCPOBOP have suggested that CAR activation directly
      leads to cell proliferation. Survival was significantly lower in the CAR+/+ mice
      fed the MCD diet in comparison with the CAR-/- mice. Taken together, these
      results suggest that CAR may therefore play a critical role in the
      hepatocarcinogenesis of the murine NASH model via the upregulation of cell
      proliferation.

PMID- 21173432
TI  - beta-catenin-independent WNT signaling in basal-like breast cancer and brain
      metastasis.
AB  - A role of WNT signaling for primary breast cancers of the basal-like subtype and
      as a predictor of brain metastasis has been described. However, a responsible WNT
      ligand has not been identified. To further clarify this question, we
      comparatively investigated 22 human breast cancer brain metastases as well as the
      highly invasive human breast cancer cell line MDA-MB-231 and the weakly motile
      MCF-7 as models for the basal-like and the luminal A subtype. WNT5A and B were
      found overexpressed in MDA-MB-231 cells as compared with MCF-7. This corresponded
      to reduction of MDA-MB-231 invasiveness by WNT inhibitors, whereas MCF-7 invasion
      was enhanced by recombinant WNT5B and abolished by WNT and Jun-N-terminal kinase
      antagonists. Expression and subcellular distribution of beta-catenin remained
      uninfluenced. Consistently, beta-catenin was not localized in the nuclei of brain
      metastases while there was strong nuclear c-Jun staining. Similar to MDA-MB-231,
      metastases showed expression of WNT5A/B and the alternative WNT receptors ROR1
      and 2. These findings were validated using external gene expression datasets
      (Gene Expression Omnibus) of different breast cancer subtypes and brain
      metastases. Hierarchical cluster analysis yielded a close relation between basal
      like cancers and brain metastases. Gene set enrichment analyses confirmed WNT
      pathway enrichment not only in basal-like primaries but also in cerebral
      metastases of all subtypes. In conclusion, WNT signaling seems highly relevant
      for basal-like and other subtypes of breast cancers metastasizing into the brain.
      beta-catenin-independent WNT signaling, presumably via ROR1-2, plays a major role
      in this context.

PMID- 21173433
TI  - Estrogen receptor alpha pathway is involved in leptin-induced ovarian cancer cell
      growth.
AB  - Previously, we demonstrated that leptin, a pleiotropic hormone produced by
      adipocytes, stimulates the growth of BG-1 ovarian cancer cells via the
      extracellular signal-regulated kinase signaling pathway. In this study, we
      further investigated the involvement of estrogen receptor (ER) pathway in the
      mechanism of leptin-induced ovarian cancer cell growth. Treatment with leptin
      (100 ng/ml) resulted in a significant increase in the cell growth of ERalpha
      transfected OVCAR-3 and A2780 cells, whereas no significant difference was
      observed in ERbeta-transfected cells. Downregulation of ERalpha using small
      interfering RNA completely reversed leptin-induced growth of BG-1 cells.
      Treatment with leptin resulted in ER transcriptional activation, i.e. nuclear
      localization of ER and increased expression of pS2, an estrogen-dependent gene.
      Luciferase reporter assay revealed that treatment of BG-1 cells with leptin (100
      ng/ml) stimulated the expression of the reporter gene in the absence of estradiol
      (E2). To examine an involvement of Janus kinase 2/signal transducers and
      activators of transcription 3 (STAT-3) and phosphatidyl-inositol 3-kinase
      (PI3K)/Akt in leptin-induced pathway, we demonstrated that leptin increased
      phosphorylation of STAT-3 and Akt in BG-1 cells in a time- and dose-dependent
      manner. On the other hand, leptin-induced cell growth and ER transactivation were
      effectively blocked by specific STAT-3 inhibitor AG490 and, to a lesser extent,
      by PI3K inhibition. Further study with coimmunoprecipitation assay revealed that
      stimulation with leptin induced STAT-3 binding to ERalpha. Taken together, these
      results indicate that the stimulation of ovarian cancer cell growth by leptin
      involves, at least in part, ER transcriptional activation via the STAT-3
      signaling pathways.

PMID- 21173435
TI  - Safrole induces apoptosis in human oral cancer HSC-3 cells.
AB  - Phytochemicals have been used as potential chemopreventive or chemotherapeutic
      agents. However, there are data suggesting a mutagenic effect of some
      phytochemicals. We hypothesized that safrole would have anticancer effects on
      human oral squamous cell carcinoma HSC-3 cells. Safrole decreased the percentage
      of viable HSC-3 cells via induction of apoptosis by an increased level of
      cytosolic Ca(2+) and a reduction in the mitochondrial membrane potential
      (DeltaPsi(m)). Changes in the membrane potential were associated with changes in
      the Bax, release of cytochrome c from mitochondria, and activation of downstream
      caspases-9 and -3, resulting in apoptotic cell death. In vivo studies also showed
      that safrole reduced the size and volume of an HSC-3 solid tumor on a xenograft
      athymic nu/nu mouse model. Western blotting and flow cytometric analysis studies
      confirmed that safrole-mediated apoptotic cell death of HSC-3 cells is regulated
      by cytosolic Ca(2+) and by mitochondria- and Fas-dependent pathways.

PMID- 21173434
TI  - Identification of caries risk factors in toddlers.
AB  - The purpose of this study was to identify risk factors to predict caries
      progression in toddlers in primary-healthcare settings for the cost-effective
      targeting of preventive and referral strategies. We examined 329 children (26 +/-
      6 mos old) twice, one year apart, in Indiana, USA. A 107-item structured
      interview was used to collect information from the primary caregiver and child on
      factors/beliefs/perceptions/behaviors that could affect caries development,
      transmission of bacteria, medical-dental health, and access to care. Bacterial
      levels, gingivitis, dental plaque, and caries experience were assessed. Multiple
      variable logistic regression models of caries progression toward cavitation
      included family caries experience, transmission-related behaviors, dietary
      factors, health beliefs, and lower income, but differed in selected
      predictors/predictive power by race/ethnicity. Addition of clinical variables did
      not significantly improve the prediction.

PMID- 21173436
TI  - An interdisciplinary outreach model of African American recruitment for
      Alzheimer's disease research.
AB  - PURPOSE: The African American Outreach Satellite (Satellite) provides educational
      outreach to facilitate African American recruitment for longitudinal studies at
      the Washington University Alzheimer's Disease Research Center (ADRC). This
      descriptive article characterizes the Satellite's recruitment methods, plan for
      community engagement, results of recruitment efforts, and potential for
      replication. DESIGN AND METHODS: The Satellite developed a comprehensive outreach
      and recruitment plan that identifies and addresses barriers to research
      participation. The Satellite conducts community outreach and recruitment programs
      and training for health care providers. RESULTS: Enrollment of cognitively
      healthy and mildly demented African Americans for participation in all ADRC
      studies increased following implementation of the recruitment plan. Current
      African American participation rates for ADRC studies include 39% for lumbar
      puncture, 43% for positron emission tomography with Pittsburgh Compound-B, 52%
      for magnetic resonance imaging, 95% for apolipoprotein E genotype testing, and
      100% for clinical and cognitive assessment. IMPLICATIONS: The Satellite reduces
      barriers to research participation, encourages retention through sustained
      interactions with participants and their families, and develops lasting
      partnerships with community organizations and health professionals who care for
      African American elders.

PMID- 21173437
TI  - Self-report measure of psychological abuse of older adults.
AB  - PURPOSE: This study tested key psychometric properties of the Older Adult
      Psychological Abuse Measure (OAPAM), one self-report scale of the Older Adult
      Mistreatment Assessment (OAMA). DESIGN AND METHODS: Items and theory were
      developed in a prior concept mapping study. Subsequently, the measures were
      administered to 226 substantiated clients by 22 elder abuse staff from 7 agencies
      in a full-scale field test. The resulting database was used to estimate the
      psychometric properties of the OAPAM using the Rasch item response theory model
      and traditional validation techniques. Analyses included tests for
      dimensionality, model fit, and theoretical construct validation. Results from the
      OAPAM client report were validated against the adult protective services
      substantiation decision of abuse and the elder abuse staff assessment of
      psychological abuse (PA). RESULTS: The client self-report measures met stringent
      Rasch analysis fit and unidimensionality criteria and had high person (internal
      consistency) and item reliability. The validity results supported the usefulness
      of the client measures and led to reconsideration of aspects of the hypothesized
      theoretical hierarchy. A short form was developed. Cut-points were proposed to
      distinguish levels of PA. IMPLICATIONS: The measure is now available to aid in
      the assessment of PA of older adults by both clinicians and researchers.
      Theoretical refinements developed using the Rasch item hierarchy may help to
      improve assessment and intervention.

PMID- 21173438
TI  - Joint and separate evaluation of risk reduction: impact on sensitivity to risk
      reduction magnitude in the context of 4 different risk information formats.
AB  - BACKGROUND: When people make choices, they may have multiple options presented
      simultaneously or, alternatively, have options presented 1 at a time. It has been
      shown that if decision makers have little experience with or difficulties in
      understanding certain attributes, these attributes will have greater impact in
      joint evaluations than in separate evaluations. The authors investigated the
      impact of separate versus joint evaluations in a health care context in which
      laypeople were presented with the possibility of participating in risk-reducing
      drug therapies. METHODS: In a randomized study comprising 895 subjects aged 40 to
      59 y in Odense, Denmark, subjects were randomized to receive information in terms
      of absolute risk reduction (ARR), relative risk reduction (RRR), number needed to
      treat (NNT), or prolongation of life (POL), all with respect to heart attack, and
      they were asked whether they would be willing to receive a specified treatment.
      Respondents were randomly allocated to valuing the interventions separately
      (either great effect or small effect) or jointly (small effect and large effect).
      RESULTS: Joint evaluation reduced the propensity to accept the intervention that
      offered the smallest effect. Respondents were more sensitive to scale when faced
      with a joint evaluation for information formats ARR, RRR, and POL but not for
      NNT. Evaluability bias appeared to be most pronounced for POL and ARR.
      CONCLUSION: Risk information appears to be prone to evaluability bias. This
      suggests that numeric information on health gains is difficult to evaluate in
      isolation. Consequently, such information may bear too little weight in separate
      evaluations of risk-reducing interventions.

PMID- 21173439
TI  - Iris Matching Based on Personalized Weight Map.
AB  - Iris recognition typically involves three steps, namely, iris image
      preprocessing, feature extraction, and feature matching. The first two steps of
      iris recognition have been well studied, but the last step is less addressed.
      Each human iris has its unique visual pattern and local image features also vary
      from region to region, which leads to significant differences in robustness and
      distinctiveness among the feature codes derived from different iris regions.
      However, most state-of-the-art iris recognition methods use a uniform matching
      strategy, where features extracted from different regions of the same person or
      the same region for different individuals are considered to be equally important.
      This paper proposes a personalized iris matching strategy using a class-specific
      weight map learned from the training images of the same iris class. The weight
      map can be updated online during the iris recognition procedure when the
      successfully recognized iris images are regarded as the new training data. The
      weight map reflects the robustness of an encoding algorithm on different iris
      regions by assigning an appropriate weight to each feature code for iris
      matching. Such a weight map trained by sufficient iris templates is convergent
      and robust against various noise. Extensive and comprehensive experiments
      demonstrate that the proposed personalized iris matching strategy achieves much
      better iris recognition performance than uniform strategies, especially for poor
      quality iris images. 

PMID- 21173440
TI  - Graph Regularized Nonnegative Matrix Factorization for Data Representation.
AB  - Matrix factorization techniques have been frequently applied in information
      retrieval, computer vision, and pattern recognition. Among them, Nonnegative
      Matrix Factorization (NMF) has received considerable attention due to its
      psychological and physiological interpretation of naturally occurring data whose
      representation may be parts based in the human brain. On the other hand, from the
      geometric perspective, the data is usually sampled from a low-dimensional
      manifold embedded in a high-dimensional ambient space. One then hopes to find a
      compact representation,which uncovers the hidden semantics and simultaneously
      respects the intrinsic geometric structure. In this paper, we propose a novel
      algorithm, called Graph Regularized Nonnegative Matrix Factorization (GNMF), for
      this purpose. In GNMF, an affinity graph is constructed to encode the geometrical
      information and we seek a matrix factorization, which respects the graph
      structure. Our empirical study shows encouraging results of the proposed
      algorithm in comparison to the state-of-the-art algorithms on real-world
      problems. 

PMID- 21173441
TI  - Online Multiperson Tracking-by-Detection from a Single, Uncalibrated Camera.
AB  - In this paper, we address the problem of automatically detecting and tracking a
      variable number of persons in complex scenes using a monocular, potentially
      moving, uncalibrated camera. We propose a novel approach for multiperson tracking
      by-detection in a particle filtering framework. In addition to final high
      confidence detections, our algorithm uses the continuous confidence of pedestrian
      detectors and online-trained, instance-specific classifiers as a graded
      observation model. Thus, generic object category knowledge is complemented by
      instance-specific information. The main contribution of this paper is to explore
      how these unreliable information sources can be used for robust multiperson
      tracking. The algorithm detects and tracks a large number of dynamically moving
      people in complex scenes with occlusions, does not rely on background modeling,
      requires no camera or ground plane calibration, and only makes use of information
      from the past. Hence, it imposes very few restrictions and is suitable for online
      applications. Our experiments show that the method yields good tracking
      performance in a large variety of highly dynamic scenarios, such as typical
      surveillance videos, webcam footage, or sports sequences. We demonstrate that our
      algorithm outperforms other methods that rely on additional information.
      Furthermore, we analyze the influence of different algorithm components on the
      robustness. 

PMID- 21173442
TI  - Effective Unconstrained Face Recognition by Combining Multiple Descriptors and
      Learned Background Statistics.
AB  - Computer vision systems have demonstrated considerable improvement in recognizing
      and verifying faces in digital images. Still, recognizing faces appearing in
      unconstrained, natural conditions remains a challenging task. In this paper, we
      present a face-image, pair-matching approach primarily developed and tested on
      the "Labeled Faces in the Wild" (LFW) benchmark that reflects the challenges of
      face recognition from unconstrained images. The approach we propose makes the
      following contributions. 1) We present a family of novel face-image descriptors
      designed to capture statistics of local patch similarities. 2) We demonstrate how
      unlabeled background samples may be used to better evaluate image similarities.
      To this end, we describe a number of novel, effective similarity measures. 3) We
      show how labeled background samples, when available, may further improve
      classification performance, by employing a unique pair-matching pipeline. We
      present state-of-the-art results on the LFW pair-matching benchmarks. In
      addition, we show our system to be well suited for multilabel face classification
      (recognition) problem, on both the LFW images and on images from the laboratory
      controlled multi-PIE database. 

PMID- 21173443
TI  - Robust Point Set Registration Using Gaussian Mixture Models.
AB  - In this paper, we present a unified framework for the rigid and nonrigid point
      set registration problem in the presence of significant amounts of noise and
      outliers. The key idea of this registration framework is to represent the input
      point sets using Gaussian mixture models. Then, the problem of point set
      registration is reformulated as the problem of aligning two Gaussian mixtures
      such that a statistical discrepancy measure between the two corresponding
      mixtures is minimized. We show that the popular iterative closest point (ICP)
      method [1] and several existing point set registration methods [2], [3], [4],
      [5], [6], [7] in the field are closely related and can be reinterpreted
      meaningfully in our general framework. Our instantiation of this general
      framework is based on the the L2 distance between two Gaussian mixtures, which
      has the closed-form expression and in turn leads to a computationally efficient
      registration algorithm. The resulting registration algorithm exhibits inherent
      statistical robustness, has an intuitive interpretation, and is simple to
      implement. We also provide theoretical and experimental comparisons with other
      robust methods for point set registration.

PMID- 21173444
TI  - On Kleinberg's Stochastic Discrimination Procedure.
AB  - A new condition for high accuracy on test sets is given for the method of
      stochastic discrimination (SD), a pattern recognition method introduced by
      Kleinberg. This condition provides a simple explanation for the observed good
      generalization properties and overtraining-resistance. We also show that the
      method of SD remains valid if the original assumption of uniform distribution on
      a finite space for resampling is relaxed. 

PMID- 21173445
TI  - Robust Object Tracking with Online Multiple Instance Learning.
AB  - In this paper, we address the problem of tracking an object in a video given its
      location in the first frame and no other information. Recently, a class of
      tracking techniques called "tracking by detection" has been shown to give
      promising results at real-time speeds. These methods train a discriminative
      classifier in an online manner to separate the object from the background. This
      classifier bootstraps itself by using the current tracker state to extract
      positive and negative examples from the current frame. Slight inaccuracies in the
      tracker can therefore lead to incorrectly labeled training examples, which
      degrade the classifier and can cause drift. In this paper, we show that using
      Multiple Instance Learning (MIL) instead of traditional supervised learning
      avoids these problems and can therefore lead to a more robust tracker with fewer
      parameter tweaks. We propose a novel online MIL algorithm for object tracking
      that achieves superior results with real-time performance. We present thorough
      experimental results (both qualitative and quantitative) on a number of
      challenging video clips. 

PMID- 21173446
TI  - Fingerprint indexing based on Minutia Cylinder-Code.
AB  - This paper proposes a new hash-based indexing method to speed up fingerprint
      identification in large databases. A Locality-Sensitive Hashing (LSH) scheme has
      been designed relying on Minutiae Cylinder-Code (MCC), which proved to be very
      effective in mapping a minutiae-based representation (position/ angle only) into
      a set of fixed-length transformation-invariant binary vectors. A novel search
      algorithm has been designed thanks to the derivation of a numerical approximation
      for the similarity between MCC vectors. Extensive experimentations have been
      carried out to compare the proposed approach against 15 existing methods over all
      the benchmarks typically used for fingerprint indexing. In spite of the smaller
      set of features used (top performing methods usually combine more features), the
      new approach outperforms existing ones in almost all of the cases.

PMID- 21173447
TI  - Richardson-Lucy Deblurring for Scenes under a Projective Motion Path.
AB  - This paper addresses how to model and correct image blur that arises when a
      camera undergoes ego motion while observing a distant scene. In particular, we
      discuss how the blurred image can be modeled as an integration of the clear scene
      under a sequence of planar projective transformations (i.e., homographies) that
      describe the camera's path. This projective motion path blur model is more
      effective at modeling the spatially varying motion blur exhibited by ego motion
      than conventional methods based on space-invariant blur kernels. To correct the
      blurred image, we describe how to modify the Richardson-Lucy (RL) algorithm to
      incorporate this new blur model. In addition, we show that our projective motion
      RL algorithm can incorporate state-of-the-art regularization priors to improve
      the deblurred results. The projective motion path blur model, along with the
      modified RL algorithm, is detailed, together with experimental results
      demonstrating its overall effectiveness. Statistical analysis on the algorithm's
      convergence properties and robustness to noise is also provided. 

PMID- 21173448
TI  - Reading 1D Barcodes with Mobile Phones Using Deformable Templates.
AB  - Camera cellphones have become ubiquitous, thus opening a plethora of
      opportunities for mobile vision applications. For instance, they can enable users
      to access reviews or price comparisons for a product from a picture of its
      barcode while still in the store. Barcode reading needs to be robust to
      challenging conditions such as blur, noise, low resolution, or low-quality camera
      lenses, all of which are extremely common. Surprisingly, even state-of-the-art
      barcode reading algorithms fail when some of these factors come into play. One
      reason resides in the early commitment strategy that virtually all existing
      algorithms adopt: The image is first binarized and then only the binary data are
      processed. We propose a new approach to barcode decoding that bypasses
      binarization. Our technique relies on deformable templates and exploits all of
      the gray-level information of each pixel. Due to our parameterization of these
      templates, we can efficiently perform maximum likelihood estimation independently
      on each digit and enforce spatial coherence in a subsequent step. We show by way
      of experiments on challenging UPC-A barcode images from five different databases
      that our approach outperforms competing algorithms. Implemented on a Nokia N95
      phone, our algorithm can localize and decode a barcode on a VGA image (640 * 480,
      JPEG compressed) in an average time of 400-500 ms. 

PMID- 21173449
TI  - CENTRIST: A Visual Descriptor for Scene Categorization.
AB  - CENsus TRansform hISTogram (CENTRIST), a new visual descriptor for recognizing
      topological places or scene categories, is introduced in this paper. We show that
      place and scene recognition, especially for indoor environments, require its
      visual descriptor to possess properties that are different from other vision
      domains (e.g., object recognition). CENTRIST satisfies these properties and suits
      the place and scene recognition task. It is a holistic representation and has
      strong generalizability for category recognition. CENTRIST mainly encodes the
      structural properties within an image and suppresses detailed textural
      information. Our experiments demonstrate that CENTRIST outperforms the current
      state of the art in several place and scene recognition data sets, compared with
      other descriptors such as SIFT and Gist. Besides, it is easy to implement and
      evaluates extremely fast. 

PMID- 21173450
TI  - Sketch-Based Image Retrieval: Benchmark and Bag-of-Features Descriptors.
AB  - We introduce a benchmark for evaluating the performance of large-scale sketch
      based image retrieval systems. The necessary data are acquired in a controlled
      user study where subjects rate how well given sketch/image pairs match. We
      suggest how to use the data for evaluating the performance of sketch-based image
      retrieval systems. The benchmark data as well as the large image database are
      made publicly available for further studies of this type. Furthermore, we develop
      new descriptors based on the bag-of-features approach and use the benchmark to
      demonstrate that they significantly outperform other descriptors in the
      literature. 

PMID- 21173451
TI  - Drawing Contour Trees in the Plane.
AB  - The contour tree compactly describes scalar field topology. From the viewpoint of
      graph drawing, it is a tree with attributes at vertices and optionally on edges.
      Standard tree drawing algorithms emphasize structural properties of the tree and
      neglect the attributes. Applying known techniques to convey this information
      proves hard and sometimes even impossible. We present several adaptions of
      popular graph drawing approaches to the problem of contour tree drawing and
      evaluate them. We identify five esthetic criteria for drawing contour trees and
      present a novel algorithm for drawing contour trees in the plane that satisfies
      four of these criteria. Our implementation is fast and effective for contour tree
      sizes usually used in interactive systems (around 100 branches) and also produces
      readable pictures for larger trees, as is shown for an 800 branch example. 

PMID- 21173452
TI  - Autostereoscopic 3D Display with Long Visualization Depth Using Referential
      Viewing Area-Based Integral Photography.
AB  - We developed an autostereoscopic display for distant viewing of 3D computer
      graphics (CG) images without using special viewing glasses or tracking devices.
      The images are created by employing referential viewing area-based CG image
      generation and pixel distribution algorithm for integral photography (IP) and
      integral videography (IV) imaging. CG image rendering is used to generate IP/IV
      elemental images. The images can be viewed from each viewpoint within a
      referential viewing area and the elemental images are reconstructed from rendered
      CG images by pixel redistribution and compensation method. The elemental images
      are projected onto a screen that is placed at the same referential viewing
      distance from the lens array as in the image rendering. Photographic film is used
      to record the elemental images through each lens. The method enables 3D images
      with a long visualization depth to be viewed from relatively long distances
      without any apparent influence from deviated or distorted lenses in the array. We
      succeeded in creating an actual autostereoscopic images with an image depth of
      several meters in front of and behind the display that appear to have 3D even
      when viewed from a distance. 

PMID- 21173453
TI  - A Hexahedral Multigrid Approach for Simulating Cuts in Deformable Objects.
AB  - We present a hexahedral finite element method for simulating cuts in deformable
      bodies using the corotational formulation of strain at high computational
      efficiency. Key to our approach is a novel embedding of adaptive element
      refinements and topological changes of the simulation grid into a geometric
      multigrid solver. Starting with a coarse hexahedral simulation grid, this grid is
      adaptively refined at the surface of a cutting tool until a finest resolution
      level, and the cut is modeled by separating elements along the cell faces at this
      level. To represent the induced discontinuities on successive multigrid levels,
      the affected coarse grid cells are duplicated and the resulting connectivity
      components are distributed to either side of the cut. Drawing upon recent work on
      octree and multigrid schemes for the numerical solution of partial differential
      equations, we develop efficient algorithms for updating the systems of equations
      of the adaptive finite element discretization and the multigrid hierarchy. To
      construct a surface that accurately aligns with the cuts, we adapt the splitting
      cubes algorithm to the specific linked voxel representation of the simulation
      domain we use. The paper is completed by a convergence analysis of the finite
      element solver and a performance comparison to alternative numerical solution
      methods. These investigations show that our approach offers high computational
      efficiency and physical accuracy, and that it enables cutting of deformable
      bodies at very high resolutions. 

PMID- 21173454
TI  - Graph Drawing Aesthetics-Created by Users, Not Algorithms.
AB  - Prior empirical work on layout aesthetics for graph drawing algorithms has
      concentrated on the interpretation of existing graph drawings. We report on
      experiments which focus on the creation and layout of graph drawings:
      participants were asked to draw graphs based on adjacency lists, and to lay them
      out "nicely." Two interaction methods were used for creating the drawings: a
      sketch interface which allows for easy, natural hand movements, and a formal
      point-and-click interface similar to a typical graph editing system. We find, in
      common with many other studies, that removing edge crossings is the most
      significant aesthetic, but also discover that aligning nodes and edges to an
      underlying grid is important. We observe that the aesthetics favored by
      participants during creation of a graph drawing are often not evident in the
      final product and that the participants did not make a clear distinction between
      the processes of creation and layout. Our results suggest that graph drawing
      systems should integrate automatic layout with the user's manual editing process,
      and provide facilities to support grid-based graph creation. 

PMID- 21173455
TI  - Six Degrees-of-Freedom Haptic Interaction with Fluids.
AB  - We often interact with fluids in our daily life, either through tools such as
      when holding a glass of water or directly with our body when we swim or we wash
      our hands. Multimodal interactions with virtual fluids would greatly improve the
      simulations realism, particularly through haptic interaction. However, achieving
      realistic, stable, and real-time force feedback from fluids is particularly
      challenging. In this work, we propose a novel approach that allows real-time six
      Degrees of Freedom (DoF) haptic interaction with fluids of variable viscosity.
      Our haptic rendering technique, based on a Smoothed-Particle Hydrodynamics
      physical model, provides a realistic haptic feedback through physically based
      forces. 6DoF haptic interaction with fluids is made possible thanks to a new
      coupling scheme and a unified particle model, allowing the use of arbitrary
      shaped rigid bodies. Particularly, fluid containers can be created to hold fluid
      and hence transmit to the user force feedback coming from fluid stirring,
      pouring, shaking, and scooping, to name a few. Moreover, we adapted an existing
      visual rendering algorithm to meet the frame rate requirements of the haptic
      algorithms. We evaluate and illustrate the main features of our approach through
      different scenarios, highlighting the 6DoF haptic feedback and the use of
      containers. 

PMID- 21173456
TI  - Visual Analysis of Large Graphs Using (X,Y)-Clustering and Hybrid Visualizations.
AB  - Many different approaches have been proposed for the challenging problem of
      visually analyzing large networks. Clustering is one of the most promising. In
      this paper, we propose a new clustering technique whose goal is that of producing
      both intracluster graphs and intercluster graph with desired topological
      properties. We formalize this concept in the (X,Y) -clustering framework, where Y
      is the class that defines the desired topological properties of intracluster
      graphs and X is the class that defines the desired topological properties of the
      intercluster graph. By exploiting this approach, hybrid visualization tools can
      effectively combine different node-link and matrix-based representations,
      allowing users to interactively explore the graph by expansion/contraction of
      clusters without loosing their mental map. As a proof of concept, we describe the
      system Visual Hybrid (X,Y)-clustering (VHYXY) that implements our approach and we
      present the results of case studies to the visual analysis of social networks. 

PMID- 21173457
TI  - Bilateral normal filtering for mesh denoising.
AB  - Decoupling local geometric features from the spatial location of a mesh is
      crucial for feature-preserving mesh denoising. This paper focuses on first order
      features, i.e., facet normals, and presents a simple yet effective anisotropic
      mesh denoising framework via normal field denoising. Unlike previous denoising
      methods based on normal filtering, which process normals defined on the Gauss
      sphere, our method considers normals as a surface signal defined over the
      original mesh. This allows the design of a novel bilateral normal filter that
      depends on both spatial distance and signal distance. Our bilateral filter is a
      more natural extension of the elegant bilateral filter for image denoising than
      those used in previous bilateral mesh denoising methods. Besides applying this
      bilateral normal filter in a local, iterative scheme, as common in most of
      previous works, we present for the first time a global, noniterative scheme for
      an isotropic denoising. We show that the former scheme is faster and more
      effective for denoising extremely noisy meshes while the latter scheme is more
      robust to irregular surface sampling. We demonstrate that both our feature
      preserving schemes generally produce visually and numerically better denoising
      results than previous methods, especially at challenging regions with sharp
      features or irregular sampling.

PMID- 21173458
TI  - Learning a 3D Human Pose Distance Metric from Geometric Pose Descriptor.
AB  - Estimating 3D pose similarity is a fundamental problem on 3D motion data. Most
      previous work calculates L2-like distance of joint orientations or coordinates,
      which does not sufficiently reflect the pose similarity of human perception. In
      this paper, we present a new pose distance metric. First, we propose a new rich
      pose feature set called Geometric Pose Descriptor (GPD). GPD is more effective in
      encoding pose similarity by utilizing features on geometric relations among body
      parts, as well as temporal information such as velocities and accelerations.
      Based on GPD, we propose a semisupervised distance metric learning algorithm
      called Regularized Distance Metric Learning with Sparse Representation (RDSR),
      which integrates information from both unsupervised data relationship and labels.
      We apply the proposed pose distance metric to applications of motion transition
      decision and content-based pose retrieval. Quantitative evaluations demonstrate
      that our method achieves better results with only a small amount of human labels,
      showing that the proposed pose distance metric is a promising building block for
      various 3D-motion related applications. 

PMID- 21173459
TI  - Determination of glycan structure from tandem mass spectra.
AB  - Glycans are molecules made from simple sugars that form complex tree structures.
      Glycans constitute one of the most important protein modifications and
      identification of glycans remains a pressing problem in biology. Unfortunately,
      the structure of glycans is hard to predict from the genome sequence of an
      organism. In this paper, we consider the problem of deriving the topology of a
      glycan solely from tandem mass spectrometry (MS) data. We study, how to generate
      glycan tree candidates that sufficiently match the sample mass spectrum, avoiding
      the combinatorial explosion of glycan structures. Unfortunately, the resulting
      problem is known to be computationally hard. We present an efficient exact
      algorithm for this problem based on fixed-parameter algorithmics that can process
      a spectrum in a matter of seconds. We also report some preliminary results of our
      method on experimental data, combining it with a preliminary candidate evaluation
      scheme. We show that our approach is fast in applications, and that we can reach
      very well de novo identification results. Finally, we show how to count the
      number of glycan topologies for a fixed size or a fixed mass. We generalize this
      result to count the number of (labeled) trees with bounded out degree, improving
      on results obtained using Polya's enumeration theorem.

PMID- 21173461
TI  - Reactions between rubidium atoms and C6F6, C2Cl4, C2HCl3, CH2=CCl2 or trans
      C2H2Cl2 in crossed molecular beams.
AB  - Molecular and fragment negative ions are produced from the collisions between
      rubidium atoms and several kinds of halogenated unsaturated organic molecules in
      crossed supersonic beams. Their apparent electron affinities and the bond
      dissociation energies are measured.

PMID- 21173460
TI  - Nonparametric clustering for studying RNA conformations.
AB  - The local conformation of RNA molecules is an important factor in determining
      their catalytic and binding properties. The analysis of such conformations is
      particularly difficult due to the large number of degrees of freedom, such as the
      measured torsion angles per residue and the interatomic distances among
      interacting residues. In this work, we use a nearest-neighbor search method based
      on the statistical mechanical Potts model to find clusters in the RNA
      conformational space. The proposed technique is mostly automatic and may be
      applied to problems, where there is no prior knowledge on the structure of the
      data space in contrast to many other clustering techniques. Results are reported
      for both single residue conformations, where the parameter set of the data space
      includes four to seven torsional angles, and base pair geometries, where the data
      space is reduced to two dimensions. Moreover, new results are reported for base
      stacking geometries. For the first two cases, i.e., single residue conformations
      and base pair geometries, we get a very good match between the results of the
      proposed clustering method and the known classifications with only few
      exceptions. For the case of base stacking geometries, we validate our
      classification with respect to geometrical constraints and describe the content,
      and the geometry of the new clusters.

PMID- 21173462
TI  - Determination of fesoterodine in pharmaceutical formulations by using liquid
      chromatography-tandem mass spectrometry.
AB  - A simple, fast, sensitive, and specific liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method for the analysis of fesoterodine (FESO) in
      pharmaceutical formulations was developed and validated using manidipine as
      internal standard (IS). The LC-MS/MS method was carried out on a Luna C8(2)
      column (50 mm * 3.0 mm i.d., um) with a mobile-phase consisting of methanol/0.1%
      formic acid (90:10, v/v). The mass spectrometry method was performed employing a
      positive electrospray ionization technique, operating in multiple reaction
      monitoring mode (MRM), monitoring the transitions of 412.2->223.0 and 611.1
      >167.0 for FESO and IS, respectively. The total analysis time was 2 min and it
      was linear in the concentration range of 5-1000 ng mL(-1). Placebo solution and
      mobile-phase components were evaluated on the specificity test and did not
      interfere with the analyte or the IS. Intra-day and inter- day precision and
      accuracy evaluated by RSDs and relative errors, respectively, were lower than 5%
      for all analytes. The method proved to be robust by a fractional factorial design
      evaluation. The proposed method was successfully applied for the quantitative
      analysis of FESO in tablet formulations to support the quality control.

PMID- 21173463
TI  - Characterization and sequence identification of angiotensin II by a novel method
      involving ultra-fast liquid chromatography assay coupled with matrix-assisted
      laser desorption/ionization quadrupole ion trap time-of-flight five tandem mass
      spectrometry analysis.
AB  - High-throughput proteomics aims to investigate dynamically changing proteins
      expressed by a full organism, specific tissue or cellular compartment under
      certain conditions. High-sensitivity mass spectrometry has gradually become a
      significant tool for characterizing peptides. Here, we analyzed angiotensin II
      using ultra-fast liquid chromatography (UFLC) coupled with matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS). First, we
      applied UFLC in isolating and collecting the angiotensin II, and then Axima
      Resonance (MALDI-QIT-ToF MS(5)) was adopted, which enables collision-induced
      dissociation-MS(5) analysis for fine structural characterization of angiotensin
      II. Resultant MS, MS(2), MS(3) and MS(4) spectra of interested [M+H](+) ions
      selected as precursor ions yielded detailed information about the sites of
      fragmentation as well as the amino acid sequence for angiotensin II; meanwhile,
      the average deviation between theoretical mass and actually measured mass from MS
      to MS(5) spectra was only 0.32 Da. It indicated that Axima-Resonance was capable
      of analyzing the peptide sequence accurately and provide the corresponding
      fragmentation information thoroughly, thus suggesting a potential strategy
      involving UFLC assay coupled with MALDI-QIT-ToF MS(5) analysis on high-throughput
      proteomics study in future.

PMID- 21173464
TI  - Determination of glycyrrhizin in dog plasma by liquid chromatography-mass
      spectrometry and its application in pharmacokinetic studies.
AB  - A sensitive liquid chromatography-electrospray ionization-mass spectrometry (LC
      ESI-MS) method was established and validated for the determination of
      glycyrrhizin in dog plasma. After treatment with methanol to precipitate
      proteins, plasma samples were analyzed on a reversed-phase C18 (ODS) column with
      a mobile phase of methanol:1% formic acid solution (75:25, v/v). MS determination
      was performed using negative electrospray ionization (negative ESI) in the
      selected ion monitoring mode. Glycyrrhizin was monitored at the m/z 821 channel
      and internal standard (gliquidone) at the m/z 526 channel. The calibration curve
      was linear over the range from 0.05 ug mL(-1) to 10 ug mL(-1) with a correlation
      coefficient above 0.99. This method was successfully applied to the
      pharmacokinetic studies in beagle dogs. The absolute bioavailability of
      glycyrrhizin in beagle dogs was 3.24%.

PMID- 21173465
TI  - Effects of transition metal ion identity and pi-cation interactions in metal
      bis(peptide) complexes containing phenylalanine.
AB  - Electrospray ionization-tandem mass spectrometry was used to study the effects of
      the metal ion identity and pi-cation interactions on the dissociation pathways of
      metal-bis(peptide) complexes, where the metal is either Mn(2+), Co(2+), Ni(2+),
      Cu(2+), or Zn(2+); and the peptide is either FGGF, GGGG, GF, or GG, where G is
      glycine and F is phenylalanine. The [(FGGF)(FGGF-H) + M(2+)](+) and [(GGGG)(GGGG
      H) + M(2+)](+) complexes dissociated by losing one FGGF or GGGG, respectively.
      Relative binding affinities were measured using the crossover points, where the
      parent and product ions were equal in ion abundance and a normalized-collision
      energy scale. The results indicate the relative binding affinities for FGGF and
      GGGG follow the same order with respect to the transition metal ion identity:
      Cu(2+) < Ni(2+) < Mn(2+) ~ Zn(2+) < Co(2+), and the pi-cation interactions in the
      FGGF complex have a measureable stabilizing effect. In contrast, the main
      fragmentation channels of [(GF)(GF-H) + M(2+)]+ and [(GG)(GG-H) + M(2+)](+) are
      loss of CO(2) and 2CO(2) with the [(GF)(GF-H) + M(2+)](+) complex also exhibiting
      cinnamic acid ,GF, residual glycine, cinnamate and styrene loss.

PMID- 21173466
TI  - Tracking traces of transition metals present in concrete mixtures by inductively
      coupled plasma mass spectrometry studies.
AB  - Transition metals can have a significant impact in research related to the dosage
      optimization of superplasticizers. It is known that the presence of transition
      metals can influence such doses, and the application of a contemporary
      instrumental method to obtain the profiles of subsisting transition elements in
      concrete mixtures would be useful. In this work, inductively-coupled plasma mass
      spectrometry (ICP-MS) is investigated as a possible tool to track traces of
      transition metals in concrete mixtures. Depth profiling using ICP-MS on proofed
      and unproofed concrete shows the presence of Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu
      and Zn at trace intensities in the bulk of the samples under investigation. The
      study demonstrates that the transition metals present in the concrete sample are
      largely a part of the cement composition and, to a minor degree, a result of
      exposure to the seawater after curing. The coated concrete samples have a metal
      distribution pattern similar to the uncoated samples, but slight differences in
      intensity bear testimony to the very low levels that originate from the exposure
      to seawater. While X-ray diffraction fails to detect these traces of metals, ICP
      MS is successful in detecting ultra-trace intensities to parts per trillion. This
      method is not only a useful application to track traces of transition metals in
      concrete, but also provides information to estimate the pore size distribution in
      a given sample by very simple means.

PMID- 21173467
TI  - Selective isolation-detection of two different positively charged peptides groups
      by strong cation exchange chromatography and matrix-assisted laser
      desorption/ionization mass spectrometry: application to proteomics studies.
AB  - We report here a procedure for the independent analysis of two groups of peptides
      by liquid chromatography-matrix-assisted laser desorption/ionization mass
      spectrometry (LC-MALDI MS/MS), using a selective isolation-detection procedure.
      In this procedure all primary amino groups of tryptic peptides derived from mouse
      liver proteins are blocked, restricting their positive charge, at acidic pH, to
      the presence of histidine and arginine residues. After strong cation exchange
      chromatography, multiply charged peptides (R + H > 1) are retained on the column
      and separated with high selectivity from singly (R + H = 1) and neutral peptides
      (R + H = 0) which are together collected in the flow-through. Using LC-MALDI
      MS/MS analysis, the retained fraction displayed a 94% of enrichment of multiply
      charged peptides while in the flow-through; peptides with at least one arginine
      or histidine residue were exclusively identified, which suggests that MS
      detection in this fraction is restricted only to those peptides with ionizable
      side chains, arginine and histidine amino acids.

PMID- 21173469
TI  - Ab initio reconstruction of difference densities by charge flipping.
AB  - The charge-flipping algorithm in its band-flipping variant is capable of ab
      initio reconstructions of scattering densities with positive and negative values.
      It is shown that the method can be applied to reconstructions of difference
      electron densities of superstructures, i.e. densities obtained as a difference
      between the true scattering density and the average density over two or more
      subcells of the true structure. The amplitudes of reflections lying on the
      reciprocal lattice of the subcell are not required for the procedure. A series of
      examples shows applications of the method to the solution of superstructures in
      periodic crystals or quasicrystals as well as the application to ab initio
      solution of modulation of an incommensurately modulated structure from satellite
      reflections only and solution of a structure from a crystal twinned by reticular
      pseudomerohedry. The method is especially suited for solving pseudosymmetry
      problems occurring frequently in superstructures.

PMID- 21173468
TI  - Geometric properties of nucleic acids with potential for autobuilding.
AB  - Medium- to high-resolution X-ray structures of DNA and RNA molecules were
      investigated to find geometric properties useful for automated model building in
      crystallographic electron-density maps. We describe a simple method, starting
      from a list of electron-density 'blobs', for identifying backbone phosphates and
      nucleic acid bases based on properties of the local electron-density
      distribution. This knowledge should be useful for the automated building of
      nucleic acid models into electron-density maps. We show that the distances and
      angles involving C1' and the P atoms, using the pseudo-torsion angles ?eta' and
      ?theta?,' that describe the ...P-C1'-P-C1'... chain, provide a promising basis
      for building the nucleic acid polymer. These quantities show reasonably narrow
      distributions with asymmetry that should allow the direction of the phosphate
      backbone to be established.

PMID- 21173470
TI  - Practical applications of averages and differences of Friedel opposites.
AB  - The practical use of the average and difference intensities of Friedel opposites
      at different stages of structure analysis has been investigated. It is shown how
      these values may be properly and practically used at the stage of space-group
      determination. At the stage of least-squares refinement, it is shown that
      increasing the weight of the difference intensities does not improve their fit to
      the model. The correct form of the coefficients for a difference electron-density
      calculation is given. In the process of structure validation, it is further shown
      that plots of the observed and model difference intensities provide an objective
      method to evaluate the fit of the data to the model and to reveal insufficiencies
      in the intensity measurements. As a further tool for the validation of structure
      determinations, the use of the Patterson functions of the average and difference
      intensities has been investigated and their clear advantage demonstrated.

PMID- 21173471
TI  - Coincidence lattices in the hyperbolic plane.
AB  - The problem of coincidences of lattices in the space R(p,q), with p + q = 2, is
      analyzed using Clifford algebra. We show that, as in R(n), any coincidence
      isometry can be decomposed as a product of at most two reflections by vectors of
      the lattice. Bases and coincidence indices are constructed explicitly for several
      interesting lattices. Our procedure is metric-independent and, in particular, the
      hyperbolic plane is obtained when p = q = 1. Additionally, we provide a proof of
      the Cartan-Dieudonne theorem for R(p,q), with p + q = 2, that includes an
      algorithm to decompose an orthogonal transformation into a product of
      reflections.

PMID- 21173472
TI  - Generation of (3 + d)-dimensional superspace groups for describing the symmetry
      of modulated crystalline structures.
AB  - A complete table of (3 + 1)D, (3 + 2)D and (3 + 3)D superspace groups (SSGs) has
      been enumerated that corrects omissions and duplicate entries in previous tables
      of superspace groups and Bravais classes. The theoretical methods employed are
      not new, though the implementation is both novel and robust. The paper also
      describes conventions for assigning a unique one-line symbol for each group in
      the table. Finally, a new online data repository is introduced that delivers more
      complete information about each SSG than has been presented previously.

PMID- 21173473
TI  - PVMR: assembling small helix fragments as structural solutions for molecular
      replacement.
AB  - A new real-space implementation of the molecular-replacement method is described.
      The method locates the search model in the target crystal by maximizing the
      matching between the search-model vectors and the Patterson self and cross
      vectors. In previous work, a new rotation function was introduced for the
      molecular-replacement method [Jiang (2008). Acta Cryst. D64, 561-566]. This
      rotation function is calculated by matching the search model directly with both
      the Patterson self and cross vectors in real space. All the matches are summed
      and averaged to enhance the overall signal-to-noise ratio for a given orientation
      of the search model. Recently, to avoid the dependence of the weights derived
      from the linear regression on the properties of the search model and the target
      crystal structure, such as secondary structures, space groups and cell
      parameters, a dynamic correlation coefficient has been designed and used as the
      total rotation function score [Jiang & Ding (2010). Chin. Phys. B, 19, 106101].
      This work further extends this idea to the implementation of translation search.
      A new real- or direct-space translation function has been implemented by matching
      the cross vectors between the symmetry mates of the search model to the Patterson
      cross vectors. This method enables effective searching for small helix fragments
      in the target crystal. Although the solution model assembled by using multiple
      fragments of helix is insufficient to start ab initio phasing of the target
      crystal, it can be used to identify the known protein folds in the Protein Data
      Bank that are homologous to the target structure. It can also be combined with
      other experimental and theoretical models to screen and select for better search
      models for molecular replacement.

PMID- 21173474
TI  - Patterson-function direct methods for structure determination of organic
      compounds from powder diffraction data. XVI.
AB  - A new type of direct methods (DM) called Patterson-function DM are presented that
      directly explore the Patterson instead of the modulus function. Since they work
      with the experimental intensities, they are particularly well suited for handling
      powder diffraction data. These methods are based on the maximization of the sum
      function S(P) ? ?H(I(H)-<I>)G(-H)(Phi) in terms of the Phi phases of the
      structure factors. The quantity accessible from the experiment is I(H), the
      equidistributed multiplet intensity of reflection H, and <I> is the average
      intensity taken over all non-systematically absent reflections. G(-H)(Phi) is the
      calculated structure-factor amplitude of the squared structure that includes the
      positivity and the atomicity of the density function in its definition. The S(P)
      sum function can be optimized with the Patterson-function tangent formula (TF)
      using a variant of the S-FFT algorithm [Rius et al. (2007), Acta Cryst. A63, 131
      134]. It is important that overlapped reflections also participate in the phase
      refinement, so that not only the resolved reflections but the whole pattern
      contribute decisively to the refinement. The increase in effective data
      resolution minimizes Fourier series termination effects and improves the accuracy
      of G(Phi). The Patterson-function TF has been applied to synchrotron powder data
      of various organic compounds. In all cases the molecules were easily identified
      in the respective Fourier maps. By way of illustration the method is applied to
      synchrotron powder data of a dimer formed by 30 symmetry-independent non-H atoms.
      Since single-crystal data may be regarded as overlap-free powder data, it is
      clear that Patterson-function DM can cope with powder and single-crystal data.

PMID- 21173475
TI  - Euclidian embeddings of periodic nets: definition of a topologically induced
      complete set of geometric descriptors for crystal structures.
AB  - Crystal-structure topologies, represented by periodic nets, are described by
      labelled quotient graphs (or voltage graphs). Because the edge space of a finite
      graph is the direct sum of its cycle and co-cycle spaces, a Euclidian
      representation of the derived periodic net is provided by mapping a basis of the
      cycle and co-cycle spaces to a set of real vectors. The mapping is consistent if
      every cycle of the basis is mapped on its own net voltage. The sum of all
      outgoing edges at every vertex may be chosen as a generating set of the co-cycle
      space. The embedding maps the cycle space onto the lattice L. By analogy, the
      concept of the co-lattice L* is defined as the image of the generators of the co
      cycle space; a co-lattice vector is proportional to the distance vector between
      an atom and the centre of gravity of its neighbours. The pair (L, L*) forms a
      complete geometric descriptor of the embedding, generalizing the concept of
      barycentric embedding. An algebraic expression permits the direct calculation of
      fractional coordinates. Non-zero co-lattice vectors allow nets with collisions,
      displacive transitions etc. to be dealt with. The method applies to nets of any
      periodicity and dimension, be they crystallographic nets or not. Examples are
      analyzed: alpha-cristobalite, the seven unstable 3-periodic minimal nets etc.

PMID- 21173476
TI  - Isomorphism of lattices of subgroups of the layer and rod groups with sublattices
      of subgroups of the space groups.
AB  - Following a brief overview of current knowledge on lattices of subgroups of the
      space groups, it is shown that in the case of reducible space groups those
      lattices contain sublattices which are lattice isomorphic to the lattices of
      subgroups of layer and rod groups. Both sublattices involve the sublattice
      consisting of equitranslational subgroups.

PMID- 21173477
TI  - On the allowed values for the triclinic unit-cell angles.
AB  - This short article questions and investigates the possible range of values for
      the three angles of a unit cell in the triclinic system. Although no constraints
      are reported in manuals and tables for crystallography, the three angles are not
      really independent; the range of allowed values is calculated and presented in
      this paper.

PMID- 21173481
TI  - A study on the contribution of body vibrations to the vibratory sensation induced
      by high-level, complex low-frequency noise.
AB  - To investigate the contribution of body vibrations to the vibratory sensation
      induced by high-level, complex low-frequency noise, we conducted two experiments.
      In Experiment 1, eight male subjects were exposed to seven types of low-frequency
      noise stimuli: two pure tones [a 31.5-Hz, 100-dB(SPL) tone and a 50-Hz, 100
      dB(SPL) tone] and five complex noises composed of the pure tones. For the complex
      noise stimuli, the sound pressure level of one tonal component was 100 dB(SPL)
      and that of another one was either 90, 95, or 100 dB(SPL). Vibration induced on
      the body surface was measured at five locations, and the correlation with the
      subjective rating of the vibratory sensation at each site of measurement was
      examined. In Experiment 2, the correlation between the body surface vibration and
      the vibratory sensation was similarly examined using seven types of noise stimuli
      composed of a 25-Hz tone and a 50-Hz tone. In both the experiments, we found that
      at the chest and the abdomen, the rating of the vibratory sensation was in close
      correlation with the vibration acceleration level (VAL) of the body surface
      vibration measured at each corresponding location. This was consistent with our
      previous results and suggested that at the trunk of the body (the chest and the
      abdomen), the mechanoreception of body vibrations plays an important role in the
      experience of the vibratory sensation in persons exposed to high-level low
      frequency noise. At the head, however, no close correlation was found between the
      rating of the vibratory sensation and the VAL of body surface vibration. This
      suggested that at the head, the perceptual mechanisms of vibration induced by
      high-level low-frequency noise were different from those in the trunk of the
      body.

PMID- 21173482
TI  - Preferred sound levels of portable music players and listening habits among
      adults: a field study.
AB  - The main purpose of this descriptive field study was to explore music listening
      habits and preferred listening levels with portable music players (PMPs). We were
      also interested in seeing whether any exposure differences could be observed
      between the sexes. Data were collected during 12 hours at Stockholm Central
      Station, where people passing by were invited to measure their preferred PMP
      listening level by using a KEMAR manikin. People were also asked to answer a
      questionnaire about their listening habits. In all, 60 persons (41 men and 19
      women) took part in the questionnaire study and 61 preferred PMP levels to be
      measured. Forty-one of these sound level measurements were valid to be reported
      after consideration was taken to acceptable measuring conditions. The women (31
      years) and the men (33 years) started to use PMPs on a regular basis in their
      early 20s. Ear canal headphones/ear buds were the preferred headphone types.
      Fifty-seven percent of the whole study population used their PMP on a daily
      basis. The measured LAeq60 sec levels corrected for free field ranged between 73
      and 102 dB, with a mean value of 83 dB. Sound levels for different types of
      headphones are also presented. The results of this study indicate that there are
      two groups of listeners: people who listen less frequently and at lower, safer
      sound levels, and people with excessive listening habits that may indeed damage
      their hearing sensory organ in time.

PMID- 21173483
TI  - The possible influence of noise frequency components on the health of exposed
      industrial workers--a review.
AB  - Noise is a common occupational health hazard in most industrial settings. An
      assessment of noise and its adverse health effects based on noise intensity is
      inadequate. For an efficient evaluation of noise effects, frequency spectrum
      analysis should also be included. This paper aims to substantiate the importance
      of studying the contribution of noise frequencies in evaluating health effects
      and their association with physiological behavior within human body.
      Additionally, a review of studies published between 1988 and 2009 that
      investigate the impact of industrial/occupational noise on auditory and non
      auditory effects and the probable association and contribution of noise frequency
      components to these effects is presented. The relevant studies in English were
      identified in Medknow, Medline, Wiley, Elsevier, and Springer publications. Data
      were extracted from the studies that fulfilled the following criteria: title
      and/or abstract of the given study that involved industrial/occupational noise
      exposure in relation to auditory and non-auditory effects or health effects.
      Significant data on the study characteristics, including noise frequency
      characteristics, for assessment were considered in the study. It is demonstrated
      that only a few studies have considered the frequency contributions in their
      investigations to study auditory effects and not non-auditory effects. The data
      suggest that significant adverse health effects due to industrial noise include
      auditory and heart-related problems. The study provides a strong evidence for the
      claims that noise with a major frequency characteristic of around 4 kHz has
      auditory effects and being deficient in data fails to show any influence of noise
      frequency components on non-auditory effects. Furthermore, specific noise levels
      and frequencies predicting the corresponding health impacts have not yet been
      validated. There is a need for advance research to clarify the importance of the
      dominant noise frequency contribution in evaluating health effects.

PMID- 21173484
TI  - Evaluation by industrial workers of passive and level-dependent hearing
      protection devices.
AB  - Level-dependent hearing protection devices (HPDs) provide protection from intense
      sound, while offering amplification for speech and other signals in lower levels
      of noise. These HPDs have been developed in response to the communication and
      operational needs of noise-exposed persons in industry and the military. This
      study was conducted to examine industrial workers' perceptions of the performance
      of two level-dependent HPDs (one with integrated radio communication capability
      and one without it) and their customary passive HPDs. This research took place at
      a plastic film manufacturing plant in Rhode Island, USA, following a mixed
      measures design. Fifteen maintenance technicians at the plant evaluated the two
      level-dependent HPDs, plus their customary passive HPDs, in three separate trial
      periods. Data were collected via a questionnaire designed for this purpose. Mixed
      model analyses of variance were performed on all dependent measures. Linear and
      quadratic effect sizes were assessed with eta. Results revealed that the two
      level-dependent HPDs offered better perceived communication and situational
      awareness than the workers' customary passive HPDs. However, the level-dependent
      HPDs were rated lower than the passive HPDs in terms of usability and comfort. To
      increase workers' acceptance of level-dependent HPDs, usability issues must be
      addressed by the HPD manufacturers.

PMID- 21173485
TI  - The sound of operation and the acoustic attenuation of the Ohmeda Medical Giraffe
      OmniBedTM.
AB  - The neonatal intensive care unit (NICU) is an environment that provides premature
      and fragile infants with health provisions needed to make a complete recovery.
      Premature infants are often born before their auditory systems have had an
      opportunity to fully mature. Research has shown that the ambient acoustic
      environment in the NICU exceeds the maximum noise level recommended by the
      American Academy of Pediatrics, even after measures have been taken to decrease
      noise levels. The purpose of this study is to evaluate noise levels inside an
      Ohmeda Medical GiraffeTM OmniBedTM, the natural attenuation of the incubator, and
      the effects of modifications on attenuation and reverberation within the Giraffe
      TM OmniBedTM. The normal operation of the GiraffeTM OmniBedTM is 41.7 dBA which
      indicates a lower noise of operation than previous studies. The GiraffeTM
      OmniBedTM naturally attenuates 12 dBA. Leaving an access latch or portal door
      open causes a statistically significant (P=.001) increase in sound within the
      bassinet. All modifications in the no-noise and the noise conditions showed a
      statistically significant (P=.001) drop in L(eq) when compared to baseline.

PMID- 21173486
TI  - Hearing loss among classical-orchestra musicians.
AB  - This study intended to evaluate classical musicians' risk of hearing loss. We
      studied 63 musicians from four Helsinki classical orchestras. We measured their
      hearing loss with an audiometer, found their prior amount of exposure to sound
      and some individual susceptibility factors with a questionnaire, measured their
      present sound exposure with dosimeters, and tested their blood pressure and
      cholesterol levels, then compared their hearing loss to ISO 1999-1990's
      predictions. The musicians' hearing loss distribution corresponded to that of the
      general population, but highly exposed musicians had greater hearing loss at
      frequencies over 3 kHz than less-exposed ones. Their individual susceptibility
      factors were low. Music deteriorates hearing, but by less than what ISO 1999-1990
      predicted. The low number of individual susceptibility factors explained the
      difference, but only reduced hearing loss and not the prevalence of tinnitus.

PMID- 21173487
TI  - Noise sensitivity and hearing disability.
AB  - The aim of this study was to investigate the association of noise sensitivity
      with self-reported hearing disability and hearing levels, with consideration of
      the role of self-reported history of noise exposure and use of hearing
      protectors. The study is based on the Finnish Twin Cohort. In 1988, a noise
      questionnaire was sent to 1005 twin pairs, 1495 individuals (688 men, 807 women)
      replied. The age range was 31-88 years. Information on some potential confounders
      was obtained from the questionnaire in 1981 for the same individuals. A subsample
      of thirty-eight elderly women with noise sensitivity response from 1988 had
      audiometry data from 2000 to 2001. Noise sensitivity was associated with self
      reported hearing disability among all subjects [odds ratio (OR) 1.55, 95%
      confidence interval (CI) 1.14-2.12] and among women (OR 1.90, 95% CI 1.19-3.04),
      but no-more significantly among men (OR 1.31, 95% CI 0.86-1.98). The association
      was primarily seen among younger subjects (50 years or less). The difference
      between noise sensitive and non-noise sensitive elderly women in the average of
      thresholds at frequencies of 0.5-4 kHz in the better ear was not significant (Pr
      = 0.18). Noise sensitivity did not modify the association of hearing disability
      with the self-reported history of occupational noise exposure. Noise sensitivity
      was associated with the use of hearing protectors at work. The study shows the
      importance of recognizing the noise sensitive in noise effect studies, since
      sensitivity in annoyance has implications in most of the effect categories.

PMID- 21173488
TI  - Noise exposure of musicians of a ballet orchestra.
AB  - With over 70 dancers and its own orchestra, The National Ballet of Canada ranks
      amongst the world's top dance companies. It performs three seasons annually:
      fall, winter and summer, plus many shows of Tchaikovsky's Nutcracker. The 70
      strong orchestra plays an average of 360 hours/year including rehearsals and
      performances. Rehearsals are held at two locations: one in a ballet rehearsal
      room with little or no absorption, and the other in an acoustically treated
      location. Performances are held in the Four Seasons Centre for the Performing
      Arts in Toronto. The present survey was done at the request of the National
      Ballet, since the musicians complained of excessive sound levels and were
      concerned about possible hearing losses. The survey was performed using five
      dosimeters Quest Mod 300 during 10 performances of the ballet Romeo and Juliet by
      Sergei Prokofiev, deemed as the noisiest in the whole repertoire. Results of the
      survey indicate that the noise exposure levels from only the orchestra's
      activities do not present risk of hearing loss. Exposure due to other musical
      activities was, however, not included.

PMID- 21173489
TI  - Occupational exposure to noise and the prevalence of hearing loss in a Belgian
      military population: a cross-sectional study.
AB  - The armed forces are highly exposed to occupational noise. The aim of this study
      was to evaluate the prevalence and noise exposures associated with the severity
      of hearing loss (HL) in a Belgian military population. A cross-sectional study
      was carried out at the Centre for Medical Expertise (CME) and in four Units of
      Occupational Medicine (UOM). Hearing thresholds were determined by audiometry.
      The examination included a questionnaire on hearing-related medical history, and
      noise exposure in military and leisure time activity. A multinomial logistic
      regression model was used to assess the association of the severity of HL with
      tinnitus, with the military occupation, and with noise exposures. Of the 2055
      subjects aged 18-55 years, 661 (32.2%) had a slight HL (25-40 dB), 280 (13.6%)
      had a moderate HL (45-60 dB) and 206 (10.0%) had a severe HL (> 60 dB) of 4 and 6
      kHz for both ears. The prevalence of slight, moderate and severe HL increased
      significantly with age and was higher for subjects from Paracommando and infantry
      units. Fighting in Built-Up Area (FIBUA) training, shooting with large caliber
      weapons, and participation in military exercises were the best determinants of HL
      in this population. These results suggest that subjects from infantry and
      Paracommando units run the highest risk of HL because they are exposed to very
      loud noises in their professional life, like large caliber shooting and FIBUA
      training.

PMID- 21173490
TI  - Vuvuzelas at South African soccer matches: risks for spectators' hearing.
AB  - South African Premier Soccer League (PSL) matches are known worldwide as some of
      the noisiest recreational events. Therefore, the objectives of this study were to
      i) measure noise levels during different PSL matches; ii) measure changes in
      auditory function after attending PSL matches; and iii) determine the factors
      that increase the risk of overexposure to noise during PSL matches. The study
      used a descriptive quantitative analytical pre- and post-exposure design.
      Participants (n = 19, and n = 10) attended two PSL matches. Each participant's
      auditory function was assessed using distortion product oto-acoustic emissions
      (DPOAEs) before and after attending a PSL match. Peak and equivalent continuous
      noise levels as well as noise dose were measured during each match. Noise levels
      recorded during the poorly attended Match 1 were lesser than those of the well
      attended Match 2. Participants attending Match 2 had statistically significant
      reduction in their DPOAE amplitudes after the match (P = 0.003) than those
      attending Match 1. Vuvuzela blowers and participants seated within 1 m from them
      were most at risk of harm to their hearing with significant reduction in DPOAE
      amplitudes post the match (P = 0.002 and P = 0.008, respectively). It was
      therefore concluded that noise levels at well-attended South African PSL matches
      pose a significant risk to spectators' auditory function as shown by reduced
      DPOAE amplitude post match attendance. Three risk factors for overexposure to
      noise during the match were identified: blowing the vuvuzela, close proximity to
      the individual blowing the vuvuzela as well as spectator turnout at the match.

PMID- 21173491
TI  - Analysis of army-wide hearing conservation database for hearing profiles related
      to crew-served and individual weapon systems.
AB  - Damage-risk criteria (DRC) for noise exposures are designed to protect 95% of the
      exposed populations from hearing injuries caused by those noise exposures. The
      current DRC used by the US military follows OSHA guidelines for continuous noise.
      The current military DRC for impulse exposures follows the recommendations from
      the National Academy of Sciences--National Research Council Committee on Hearing,
      Bioacoustics, and Biomechanics (CHABA) and are contained in the current military
      standard, MIL-STD-1474D "Noise Limits." Suggesting that the MIL-STD for impulse
      exposure is too stringent, various individuals have proposed that the DRC for
      exposure to high-level impulses be relaxed. The purpose of this study is to
      evaluate the current hearing status of US Army Soldiers, some of whom can be, by
      their military occupational specialties (MOS), reasonably expected to be
      routinely exposed to high-level impulses from weapon systems. The Defense
      Occupational and Environmental Health Readiness System--Hearing Conservation
      (DOEHRS-HC) was queried for the hearing status of enlisted Soldiers of 32
      different MOSs. The results indicated that less than 95% of the Soldiers in the
      DOEHRS-HC database were classified as having normal hearing. In other words, the
      goal of the DRC used for limiting noise injuries (from continuous and impulse
      exposures) was not stringent enough to prevent hearing injuries in all but the
      most susceptible Soldiers. These results suggest that the current military noise
      DRC should not be relaxed.

PMID- 21173493
TI  - Comparison of tissue characteristics between acute coronary syndrome and stable
      angina pectoris. An integrated backscatter intravascular ultrasound analysis of
      culprit and non-culprit lesions.
AB  - BACKGROUND: Patients with acute coronary syndrome (ACS) have multiple complex
      coronary plaques associated with plaque vulnerability. The present study assessed
      the tissue characteristics of coronary plaques between ACS and stable angina
      pectoris (SAP) of culprit and non-culprit lesions using integrated backscatter
      intravascular ultrasound (IB-IVUS). METHODS AND RESULTS: IVUS was performed in
      165 patients (40 patients with ACS) with 225 culprit (65 lesions in ACS) and 171
      non-culprit lesions (42 lesions in ACS). The percentage of fibrous area (fibrous
      area/plaque area, %FIB) and the percentage of lipid area (lipid area/plaque area,
      %LIP) at the segment with minimal luminal area were calculated using IB-IVUS
      system. Culprit and non-culprit lesions with ACS showed a significant increase in
      %LIP (38+/-18 vs. 30+/-15%, P=0.002, and 38+/-21 vs. 32+/-17%, P=0.03,
      respectively) and a significant decrease in %FIB (59+/-15 vs. 63+/-12 %, P=0.04,
      and 57+/-18 vs. 62+/-14%, P=0.04, respectively) compared to those with SAP. On
      logistic regression analysis, not only culprit lesions but also non-culprit
      lesions with ACS patients were significantly associated with the lipid-rich
      plaque. CONCLUSIONS: Non-culprit coronary lesions with ACS patients are
      associated with the lipid-rich plaque, suggesting the extensive development of
      plaques instability in these patients.

PMID- 21173494
TI  - Efficacy of out-patient cardiac rehabilitation in low prognostic risk patients
      after acute myocardial infarction in primary intervention era.
AB  - BACKGROUND: The efficacy of out-patient cardiac rehabilitation (OPCR) in patients
      with a low prognostic risk after acute myocardial infarction (AMI) is unclear in
      the recent primary intervention era. METHODS AND RESULTS: A total of 637 AMI
      patients who participated in in-hospital cardiac rehabilitation were divided into
      2 groups; low prognostic risk group (n=219; age <65 years, successful
      reperfusion, Killip class I, peak serum creatine kinase <6,000U/L, and left
      ventricular ejection fraction >=40%) and non-low prognostic risk group (n=418).
      The prevalence of coronary risk factors (CRF) was compared between the 2 groups.
      Then, in the low-risk group, the efficacy of OPCR was compared between active
      OPCR participants (n=52; >=20 sessions/3 months) and non-active participants
      (n=60; <6 sessions/3 months). Compared with the non-low prognostic risk group,
      the low prognostic risk group had a significantly higher prevalence of current
      smokers (72% vs. 49%, P<0.05) and patients with multiple CRF (3 or more; 49% vs.
      39%, P<0.05). Among the low- risk group, active OPCR participants showed a
      significantly greater improvement in exercise capacity (peak VO(2), P<0.05) and
      maintained a better CRF profile (total cholesterol, triglyceride and blood
      pressure, all P<0.05) than inactive participants at 3 months. CONCLUSIONS: Low
      prognostic risk AMI patients have a higher prevalence of multiple CRF than non
      low risk patients. Even in this low risk group, active participation in OPCR is
      associated with improved exercise capacity and better CRF profile.

PMID- 21173496
TI  - Long-term outcome of coil occlusion in patients with patent ductus arteriosus.
AB  - BACKGROUND: Coil occlusion has been widely indicated for the closure of patent
      ductus arteriosus (PDA). Although many reports have shown the efficacy and safety
      of coil occlusion, the long-term outcome in patients remains controversial. Here,
      we analyzed the long-term outcome of coil occlusion in patients with PDA in
      Japan. METHODS AND RESULTS: We collected the longitudinal data of patients who
      underwent coil occlusion between 1995 and 2009. A total of 310 coil occlusions
      were performed in 298 patients with PDA. The median minimum duct diameter was
      1.4mm. Successful coil occlusion was achieved in 286 patients (96.0%), and total
      adverse events were seen in only 28 cases (9.0%). The median follow-up period was
      50 months. The occlusion rates at 1 month, 6 months, 1 year, 2 years and 5 years
      were 90.1%, 94.4%, 97.4%, 97.8% and 97.8%, respectively. Patients with a large
      PDA (>=4mm) showed a higher rate of residual leakage than those with a small
      (<2mm) or moderate (2-4mm) PDA (P=0.004). Patients who underwent this procedure
      in the early study period also showed a higher rate of residual leakage than
      those in the late study period. CONCLUSIONS: Coil occlusion is an effective
      procedure for patients with PDA. Our data indicate that the long-term outcome is
      promising without any adverse events.

PMID- 21173495
TI  - Effect of Waon therapy on oxidative stress in chronic heart failure.
AB  - BACKGROUND: A previous report by our team showed that Waon therapy, using a far
      infrared-ray dry sauna at 60 degrees C, improves cardiac and vascular function in
      patients with chronic heart failure (CHF). The purpose of the present study was
      to clarify the effect of Waon therapy on oxidative stress in CHF patients and
      investigate its mechanism by animal experiments. METHODS AND RESULTS: Forty
      patients with CHF were divided into control (n=20) and Waon therapy (n=20)
      groups. All patients received standard optimal medications for CHF. Waon therapy
      group was treated with Waon therapy daily for 4 weeks. After 4 weeks of Waon
      therapy, concentrations of hydroperoxide and brain natriuretic peptide (BNP)
      decreased significantly (hydroperoxide, 422+/-116 to 327+/-88U.CARR, P<0.001;
      BNP, 402+/-221 to 225+/-137pg/ml, P<0.001), and the nitric oxide metabolites
      increased (71.2+/-35.4 to 92.0+/-40.5mmol/L, P<0.05). In contrast, none of these
      variables changed over the 4-week interval in the control group. Furthermore,
      animal experiments were performed using TO-2 cardiomyopathic hamsters. On
      immunohistochemistry, cardiac expression of 4-hydroxy-2-nonenal, a marker of
      oxidative stress, was decreased in the 4-week Waon therapy compared to untreated
      hamsters. On Western blotting, cardiac expressions of heat shock protein (HSP)
      27, manganese superoxide dismutase and HSP32, which reduce oxidative stress, were
      significantly upregulated in the 4-week Waon therapy compared to untreated
      hamsters. CONCLUSIONS: Waon therapy decreases oxidative stress in patients and
      hamsters with heart failure.

PMID- 21173497
TI  - Usefulness of computed tomographic pulmonary angiography in the risk
      stratification of acute pulmonary thromboembolism. Comparison with cardiac
      biomarkers.
AB  - BACKGROUND: To evaluate the usefulness of computed tomographic pulmonary
      angiographic (CTPA) variables in the risk stratification of acute pulmonary
      thromboembolism (APE) and compare these variables with cardiac biomarkers.
      METHODS AND RESULTS: Eighty consecutive patients with APE were divided into
      patients with right ventricular (RV) dysfunction (n=49, 62.1+/-15.1 years, 31
      females) vs. patients without RV dysfunction (n=31, 67.7+/-13.7 years, 18
      females). CTPA variables were analyzed and compared with cardiac biomarkers. The
      ratio of right to left ventricular dimension (RVD/LVD), CT index of PA clot load,
      contrast reflux to the inferior vena cava (IVC), and ventricular septal bowing
      (VSB) were significantly different CTPA variables between the groups. These
      variables were also significantly associated with cardiac biomarkers. By receiver
      operation characteristic curve analysis, the area under the curve to predict RV
      dysfunction was 0.863 for RVD/LVD, 0.841 for PA clot load, 0.744 for contrast
      reflux to IVC, and 0.635 for VSB. The optimal cut-off value to predict RV
      dysfunction was 1.12 for RVD/LVD (sensitivity: 89.8%, specificity: 77.4%) and
      19.5 for PA clot load (sensitivity: 81.6%, specificity: 77.4%). CONCLUSIONS:
      RVD/LVD, PA clot load, contrast reflux to IVC, and VSB on CTPA were significantly
      associated with RV dysfunction and cardiac biomarkers in APE. The present study
      demonstrated that CTPA is useful not only in the diagnosis, but also in the risk
      stratification of APE.

PMID- 21173498
TI  - Clinical and angiographic outcomes with sirolimus-eluting stent for coronary
      bifurcation lesions. The J-PMS study.
AB  - BACKGROUND: Long-term outcomes of patients with bifurcated lesions and the
      restenotic response of the side branches after sirolimus-eluting stent (SES)
      implantation, comparing 1-stent with 2-stent treatment, are still under
      discussion. METHODS AND RESULTS: Japan Post-Marketing Surveillance Registry (J
      PMS) is a prospective registry designed to evaluate the safety and efficacy of
      the SES in routine clinical practice. Angiograms of 1,063 patients with 1,250
      lesions were analyzed at the independent core lab. Of these, 324 patients with
      bifurcation lesions were enrolled. Clinical endpoints were assessed at 3 years.
      Both main and side branches were evaluated by quantitative coronary angiography
      at post-procedure (n=349) and 8-month follow up (n=293). Two-stent treatment was
      performed in 12% of the cases. In-segment restenosis rates at 8 months were 25.6%
      in the side branch, but newly developed restenosis was seen in only 6.8%. Late
      loss at the carina of the side branch was -0.11mm in the 1-stent group. Major
      adverse cardiovascular events rate was 18.3% at 3 years. Target-lesion
      revascularization rate up to 3 years was 21.6% in the 2-stent group and 8.7% in
      the 1-stent group (P=0.037). Stent thrombosis occurred in 6 cases (2.0%) until 3
      years. Of these, 4 cases were treated with 2-stent (10.81% vs. 0.76% in 1-stent,
      P=0.003, respectively). CONCLUSIONS: In a real-world setting, treatment of
      coronary bifurcation lesions using SES demonstrated favorable long-term outcomes
      as long as the side branch was not stented.

PMID- 21173499
TI  - Drug-eluting stents vs. bare metal stents in saphenous vein graft disease.
      Insights from a meta-analysis of 7,090 patients.
AB  - BACKGROUND: Evidence supporting the use of drug-eluting stents (DES) in saphenous
      vein graft (SVG) disease is uncertain. Previous studies have suggested that DES
      might reduce the re-intervention rate in SVG disease, with conflicting data on
      mortality. Thus, a meta-analysis was performed to compare outcomes of DES vs.
      bare metal stent (BMS) in SVG disease. METHODS AND RESULTS: Medline and Web
      databases were searched for studies comparing DES and BMS for SVG disease,
      reporting rates of overall mortality, target vessel revascularization (TVR) and
      myocardial infarction (MI) with a follow-up of >=6 months. The meta-analysis
      included 23 studies (7,090 patients). Compared with BMS, DES-treated patients had
      lower rates of TVR (odds ratio (OR), 0.53; confidence interval (CI), 0.39-0.72;
      P<0.0001) and overall mortality (OR, 0.63; CI, 0.40-0.99; P=0.05), but similar
      rates of MI (OR, 0.92; CI, 0.64-1.33; P=0.7). Subgroup analysis highlighted
      differences between non-randomized studies, in which DES improved mortality
      rates, and randomized trials, in which benefit from DES was not evident. Meta
      regression analysis showed that DES were more effective in the presence of older
      grafts and type 2 diabetes. CONCLUSIONS: The present meta-analysis showed that,
      in SVG disease, DES significantly reduced TVR, but did not provide clear benefits
      on mortality and MI, with an opposite direction of results in mortality observed
      from randomized and observational data.

PMID- 21173500
TI  - Clinical significance and impact of "painless" acute aortic dissection.

PMID- 21173501
TI  - Neointimal coverage over coronary stent struts crossing the side branch Ostia.

PMID- 21173502
TI  - An old ventricular assist device still working for patients with end-stage heart
      failure in Japan.

PMID- 21173503
TI  - What can we expect in PCI in patients with chronic coronary artery disease. -
      Indication of PCI for angiographically significant coronary artery stenosis
      without objective evidence of myocardial ischemia (Con)-.
AB  - Compared with coronary artery bypass graft surgery (CABG), similar safety and
      efficacy have been demonstrated for percutaneous coronary intervention (PCI) with
      bare metal stents (BMS), except for the inferiority of PCI to CABG for repeat
      revascularization. Drug-eluting stents (DES) have dramatically reduced in-stent
      restenosis compared with BMS, and comparable prognoses could be expected in PCI
      with DES compared with CABG. Nevertheless, the long-term prognostic effect of PCI
      on major adverse cardiovascular events (MACE) in patients with stable coronary
      artery disease (CAD) remains uncertain, so the spotlight has been focused on the
      comparative long-term results of DES and CABG. At the moment, we should know that
      previous studies have reported only that PCI decreases angina frequency and
      improves short-term exercise performance in chronic CAD patients, and it
      effectively reduces the incidence of both death and myocardial infarction (MI)
      only in patients with acute coronary syndromes. Furthermore, a recent study also
      describes no advantage in improvement of prognosis including death, MI and other
      MACE for PCI compared with aggressive medical therapy in stable CAD patients, and
      for stenotic lesions without evidence of ischemia, the benefit of
      revascularization is less clear; medical therapy alone is likely to be equally
      effective. In conclusion, based on these data we should restrain ourselves from
      lesion treatment by simple PCI for angiographically significant CAD without any
      objective evidence of myocardial ischemia.   

PMID- 21173504
TI  - Prediction of acute heart failure decompensation.

PMID- 21173505
TI  - Visual vs. quantitative assessment. - A new viewpoint for cardiac function using
      a motion tracking method.-.

PMID- 21173506
TI  - Transmural dispersion of repolarization and drug-induced Torsade de Pointes. -A 3
      D simulation study-.

PMID- 21173507
TI  - Angiography is the gold standard and objective evidence of myocardial ischemia is
      mandatory if lesion severity is questionable. - Indication of PCI for
      angiographically significant coronary artery stenosis without objective evidence
      of myocardial ischemia (Pro)-.
AB  - The indications for percutaneous coronary intervention (PCI) have expanded,
      especially after the approval of drug-eluting stents, for both complex lesions
      and those with intermediate stenosis. Because recent randomized trials have
      demonstrated the non-inferiority of optimal medical treatment for stable angina
      compared with coronary revascularization, and the benefits of PCI guided by
      coronary pressure measurement have been shown in another trial, the
      appropriateness of current indications for CI has been called into question. In
      the evaluation of coronary artery stenosis, inter- and intraobserver
      variabilities can be problematic. Therefore, the use of PCI for intermediate
      coronary stenosis based on angiographic evaluation alone without documentation of
      myocardial ischemia could be questionable. Guidelines mention that physiological
      assessment of myocardial ischemia is most useful in patients with intermediate
      coronary artery stenosis, while interobserver differences in the assessment of
      severe stenosis are usually small.Accordingly, routine provocation testing for
      myocardial ischemia before PCI maybe less than ideal for real-world practice, and
      the indications for PCI should be multifactorial. 

PMID- 21173508
TI  - Retinol-binding protein 4 and insulin resistance in preeclampsia.
AB  - Preeclampsia is characterized by the onset of high blood pressure and proteinuria
      during pregnancy, which results in substantial maternal and neonatal morbidity
      and mortality. Insulin resistance has been observed before the onset of
      preeclampsia, and is implicated in its pathophysiology. Recently, retinol-binding
      protein 4 (RBP4), which carries retinol in circulation, has been shown to be a
      potential regulator of insulin resistance originating from adipose tissue. Here
      we measured insulin resistance and RBP-4 levels in patients with preeclampsia and
      in women with normal pregnancies matched for gestational age and body mass index
      at Okayama University Hospital. Our aim was to examine the potential role of RBP4
      in the pathophysiology of this disorder. There were no significant differences in
      RBP4 levels between all patients with preeclampsia and controls. However, the
      RBP4 level and homeostasis model assessment as an index of insulin resistance
      (HOMA-IR) in overweight patients with late-onset preeclampsia were significantly
      higher than in overweight controls carrying normal pregnancies and in normal
      weight women with late-onset preeclampsia. In contrast, there were no significant
      differences between the overweight and normal weight groups among patients with
      early-onset preeclampsia and in healthy pregnant women. These data suggest that
      RBP4 might act in the pathophysiology of late-onset preeclampsia via increased
      insulin resistance in obese women.

PMID- 21173510
TI  - Transradial approach percutaneous coronary interventions in an out-patient
      clinic.
AB  - Same-day discharge transradial percutaneous coronary intervention (TRI) has been
      reported to be safe and feasible in Western countries. However, Asia has not
      produced any reports related to this matter. The present study explored the
      safety and feasibility of patients with indications for TR coronary angiography
      and ad hoc PCI with a same-day discharge protocol. Between October 1995 and
      December 2002, 660 adult patients were admitted to our hospital for ad hoc PCIs.
      Of these, 214 patients were discharged on the day of their PCI (group A), while
      the remaining 446 patients were referred for out-patient department (OPD) PCI
      with subsequent admission (group B). Periprocedural complications were not
      significantly different between the groups. There were no differences in 1-month
      major adverse cardiac events including death, myocardial infarction, and target
      vessel revascularization (1.4% versus 0.2% for groups A and B, respectively; P =
      0.068). Three group A cases (1.4%) experienced peri- and post-PCI myocardial
      infarction and one group B case (0.2%) experienced a post-PCI myocardial
      infarction. No patient died or required emergency bypass surgery. In group A, 8
      cases (3.7%) required cutting balloon angioplasty and 2 cases (0.9%) needed
      rotational atherectomy. TRI is safe and feasible on an outpatient basis. For
      select patients, even though PCI can carry the potential risk of subsequent
      cutting balloon angioplasty or rotational atherectomy, the procedure should still
      be considered.

PMID- 21173509
TI  - Prevalence of RET/PTC rearrangement in benign and malignant thyroid nodules and
      its clinical application.
AB  - Fine-needle aspiration cytology (FNAC) is the primary means to distinguish benign
      thyroid nodules from malignant ones. About 20% of FNAC yields indeterminate
      results leading to unnecessary or delayed surgery. Many studies of tissue
      samples, the majority of which are retrospective advocate testing for RET
      rearrangements as a diagnostic adjunctive tool in thyroid nodules with
      indeterminate cytological findings. Because of the uncertain prevalence of RET
      rearrangements, its utility as a tumor marker is still controversial. The goal of
      this study was to establish the prevalence and the utility of testing for RET
      rearrangements in FNAC suspicious of cancer in a clinical setting. In this
      prospective study, we analysed a large series of thyroid aspirates by RT-PCR only
      and Southern blot on RT-PCR products for type 1 and 3 RET rearrangements. Results
      were compared with clinical findings, cytological diagnosis and final
      histopathology. By the higher sensitive Southern-blot on RT-PCR method, RET
      rearrangements were present in 36% of papillary thyroid carcinomas (RET/PTC-1,
      12%; RET/PTC-3, 20%; both, 4%) and of 13.3% of benign nodules. By means of RT-PCR
      only, RET rearrangements were disclosed only in 14.3% of PTC and in 3.6% of
      benign nodules. No significant correlation was found between RET rearrangements
      and clinicopathological features of patients. These results indicate that
      molecular testing of thyroid nodules for RET/PTC must take into account of its
      high prevalence in benign nodules, inducing false positive diagnoses when the
      highly sensitive assay Southern-blot on RT-PCR is used. Its searching by means of
      RT-PCR only, has a specificity superior of conventional cytology and can be used
      to refine inconclusive FNAC.

PMID- 21173511
TI  - Long-term (4-year) outcomes and predictors of adverse cardiac events after
      sirolimus-eluting stent implantation in unprotected left main coronary artery.
AB  - The long-term safety and efficiency of sirolimus-eluting stent (SES) treatment in
      unprotected left main coronary artery (ULMCA) have not yet been ascertained.From
      2003 to 2006, 126 consecutive patients with de novo lesions in ULMCA who
      underwent SES were retrospectively analyzed in a single center in China. During 4
      year follow-up, major adverse cardiovascular event (MACE)-free survival was
      74.6%. Cardiac death occurred in 5 (4.0%), and target lesion revascularization
      (TLR) and target vessel revascularization (TVR) occurred in 15 (11.9%) and 24
      (19.0%) patients, respectively. One (0.8%) experienced probable stent thrombosis
      while 1 (0.8%) presented possible stent thrombosis. Impaired LVEF (< 40%) and
      high surgical risk (Euro score > 6) were the independent predictors of MACEs.PCI
      with SES for de novo lesions in ULMCA is feasible with a low procedural risk.
      However, SES was associated with a relatively higher rate of TLR and TVR.
      Impaired LVEF and high surgical risk were important predictors of MACEs.

PMID- 21173512
TI  - Angioscopic study of silent plaque disruption in nonischemic related coronary
      artery in patients with stable ischemic heart disease.
AB  - Plaque disruption, which may be associated with some coronary risk factors, plays
      a key role in the development of acute coronary syndromes and progression of
      atherosclerosis. However, the clinical profile of asymptomatic plaque disruption
      in stable ischemic heart disease has not been well evaluated. The aim of the
      present study was to investigate the frequency and determinants of silent plaque
      disruption (SPD) in patients with stable ischemic heart disease using coronary
      angioscopy. Forty-one patients with stable angina or old myocardial infarction
      (OMI) without any complaints within 3 months were included in the present study.
      Angioscopy was successfully performed through 49 nonischemic related coronary
      arteries. The presence of SPD and coronary risk factors were recorded. Silent
      plaque disruption was found in 12 patients with stable ischemic heart disease
      (12/41, 29.3%), and the frequency of SPD in nonischemic related coronary arteries
      was 26.5% (13/49). A significantly higher frequency of SPD was noted in yellow
      plaques than in white plaques (35.3% versus 6.7%, P = 0.043). Overall, the
      independent clinical risk factors of SPD in nonischemic related coronary arteries
      were diabetes mellitus (P = 0.018; OR, 18.8209; 95% CI, 1.6525 to 214.3523) and
      hypertension (P = 0.0313; OR, 6.6485; 95% CI, 1.1850 to 37.3019). These results
      suggest silent plaque disruption was commonly observed in nonischemic related
      coronary arteries in patients with stable ischemic heart disease and its
      determinants were diabetes mellitus and hypertension.

PMID- 21173513
TI  - Chronic frequent premature ventricular complexes originating from right and non
      right ventricular outflow tracts.
AB  - Frequent premature ventricular complexes (PVCs) from the right ventricular
      outflow tract (RVOT) have recently been reported to be a cause of dilated
      cardiomyopathy. We studied the clinical impact of the elimination of PVCs from
      RVOT and non-RVOT.Thirty-six patients with symptomatic PVCs that were treated
      with radiofrequency catheter ablation (RFCA) were studied. The patients were
      assigned to one of two groups according to the origin of the PVCs (group I, RVOT
      origin, n = 24; group II, non-RVOT-origin, n = 12) and observed for 10.5 +/- 7.1
      months.The burden of PVCs at baseline was 19.7 +/- 10.6% and 18.7 +/- 8.7% in
      group I and group II, respectively (P = 0.779). In group II, hypertension was
      more common (16.7% versus 58.3%, P = 0.020) and LV diastolic function was worse
      (Em, 8.7 +/- 3.0 versus 6.4 +/- 1.8 cm/second, P = 0.018). The LV end diastolic
      volume index (LVEDVI) decreased in both groups (59.7 +/- 14.6 to 50.9 +/- 9.6
      mL/m(2), P = 0.004 in group I; 60.0 +/- 19.9 to 51.6 +/- 12.4 mL/m(2), P = 0.044
      in group II), while the left atrial volume index (LAVI) decreased only in group I
      (36.7 +/- 11.7 to 31.7 +/- 10.0 mL/m(2), P = 0.002 in group I; 35.6 +/- 11.9 to
      33.8 +/- 10.3 mL/m(2), P = 0.317 in group II). The left ventricular ejection
      fraction (LVEF) significantly improved in both groups (51.1 +/- 6.6 to 59.8 +/-
      7.2 %, P < 0.01 in group I; 49.9 +/- 6.9 to 59.0 +/- 5.9 %, P < 0.01 in group
      II).RFCA of PVCs leads to a reduction of LV volume and improvement of LV systolic
      function regardless of the origin of the PVCs. Conversely, a non-RVOT-origin as
      well as an RVOT-origin of the PVCs can cause DCM-like changes in the left
      ventricle.

PMID- 21173514
TI  - Detection of diastolic potentials around the mitral annulus of structurally
      normal human hearts.
AB  - To examine the electrophysiologic characteristics of the subvalvular mitral
      region, we retrospectively searched for the presence of subvalvular diastolic
      potentials (DP) in 91 patients (mean age, 46.9 +/- 16.6 years) who underwent
      catheter ablation of left-sided accessory pathways (AP). We detected low
      amplitude (0.19 +/- 0.09 mV) DP in 14 patients (15.4%), including 8 with overt
      preexcitation and 6 patients with concealed AP. The mean interval between
      ventricular electrogram and DP was 383 +/- 46 ms (range, 306-475). DP were
      detected in 4 of 20 patients with antero-lateral, 3 of 38 with lateral, 4 of 12
      with postero-lateral, 2 of 14 with posterior, and 3 of 10 patients with postero
      septal AP. In 6 of 14 patients, DP were detected before ablation. In 4 of 8
      patients with overt preexcitation, DP were consistently recorded after
      elimination of the delta wave, suggesting that they were not associated with AP
      conduction. In 6 of 11 patients, DP were observed during both sinus rhythm and
      ventricular pacing, suggesting that they were not artifacts. The
      electrophysiologic characteristics of clinically relevant DP around the mitral
      annulus suggest that, in normal human hearts, an anatomical substrate may be
      present around the mitral annulus.

PMID- 21173515
TI  - Risks and benefits of combined use of bucolome and warfarin in anticoagulation
      therapy.
AB  - Although bucolome has been used empirically to enhance and stabilize warfarin
      action in some institutes, the clinical risks and benefits of this combination
      are unclear. In the present study, warfarin monotherapy (WM) and bucolome
      combination (BC) therapy were compared in anticoagulation therapy.One hundred and
      ninety-five patients indicated for anticoagulation therapy were randomly assigned
      to WM (n = 98) or BC (bucolome 300 mg/day, n = 97). The dosage of warfarin was
      optimized in each patient to maintain the international normalized ratio (INR)
      level in the appropriate zone, ie, 1.6-2.6 for lower risk and 2.0-3.0 for higher
      risk patients. The clinical characteristics, clinical events, and time in
      therapeutic range (TTR) were evaluated and compared between the two groups. TTR
      was calculated using Rosendaal's linear interpolation method.The optimal dosage
      of warfarin was 3.3 +/- 1.0 mg/day in WM and 1.4 +/- 0.5 mg/day in BC (P <
      0.001). During the observation period of 18 +/- 6 months, no serious complication
      was observed and INR was measured 11 +/- 3 times in each case. TTR was 0.61 +/-
      0.13 in WM and 0.62 +/- 0.14 in BC (NS), but TTR in the WM subgroup with warfarin
      > 3 mg (0.58 +/- 0.13) was lower than in the WM subgroup with warfarin <= 3 mg
      (0.64 +/- 0.13, P = 0.026) and BC (P = 0.042).BC reduced the optimal dosage of
      warfarin without increasing clinical events. There was no significant difference
      in TTR between WM and BC, but BC may have benefits in selected cases, such as
      warfarin resistance.

PMID- 21173516
TI  - Clinical significance of matrix metalloproteinase (MMP)-2 in patients with acute
      heart failure.
AB  - The serum levels of matrix metalloproteinases (MMPs) increase during chronic
      heart failure (HF) and the MMP-2 are related to a poor prognosis. However, the
      roles of MMP-2 in acute HF (AHF) remain unclear. We investigated the change and
      clinical significance of MMP-2 in these conditions. The serum levels of MMP-2
      were measured in 83 AHF patients before starting treatment (day 1), 3 (day 3) and
      7 (day 7) days after admission, and before discharge (predischarge). MMP-2
      decreased rapidly and significantly from day 3 to day 1 (902.9 +/- 304.2 versus
      1220.4 +/- 330.5 ng/mL; P < 0.0001), whereas that of MMP-2 was not significantly
      different on day 7 and at predischarge (894.7 +/- 278.9 and 920.0 +/- 269.6
      ng/mL, respectively) compared to day 3. We evaluated the relationships between
      DeltaMMPs, defined as the changes in MMPs from day 1 to day 3 and HF events
      including cardiac death, readmission to hospital for HF, and uncontrollable HF.
      The MMP-2 value was significantly (P = 0.004) more decreased in the event-free
      group (381.4 +/- 256.5 ng/mL) than in the event group (211.9 +/- 225.5 ng/mL)
      between day 1 and day 3. The results of the multivariate logistic regression
      model for predicting HF events found that the specific factor for HF events was
      DeltaMMP-2. Cutoff values of DeltaMMP-2 were determined and event-free curves
      were constructed. Kaplan-Meier curves showed that the prognosis was significantly
      better among the patients with reductions in DeltaMMP-2 values of more than 342
      ng/mL. The serum levels of MMP-2 decreased with improvements in AHF. Rapid
      decreases in MMP-2 may be important for a better clinical outcome in patients
      with AHF.

PMID- 21173517
TI  - Baroreflex sensitivity might predict responders to milrinone in patients with
      heart failure.
AB  - The phosphodiesterase III inhibitor milrinone (MIL) is considered to be effective
      for "wet and cold" heart failure. In some cases, however, the inotropic effects
      of milrinone are insufficient. A previous study suggested that baroreflex
      sensitivity (BRS) predicts the cases in which MIL increases left ventricular
      dp/dt. The aim of this study was to determine whether BRS measured using the
      spontaneous sequence method predicts the MIL responders. Twenty-four patients
      with "wet and cold" heart failure whose systolic blood pressure > 100 mmHg were
      enrolled. At 2 hours MIL improved dys-pnea, general fatigue, urine volume, and
      tricuspid regurgitant pressure gradient in 13 patients (responders; R group),
      whereas it failed to improve in 11 patients (nonresponders; NR group). BRS in the
      R group was significantly higher than that in the NR group prior to the MIL
      infusion. At 2 hours after the MIL infusion, BRS was further increased in the R
      group, but did not increase in the NR group. The sensitivity and specificity of
      BRS at a cut-off level of 5 ms/mmHg for the prediction of R group were 0.94 and
      0.93, respectively. BRS might be useful for identifying potential responders to
      milrinone in patients with blood pressure-preserved "wet and cold" heart failure.

PMID- 21173518
TI  - Comparison of biomarkers for predicting disease severity and long-term
      respiratory prognosis in patients with acute pulmonary embolism.
AB  - Biomarkers are needed for early risk stratification and improved inpatient
      management to obtain better outcomes in acute pulmonary embolism (PE) patients.
      The aim of the present study was to evaluate biomarkers of right ventricular
      dysfunction (RVD) in order to predict a complicated clinical course and long-term
      respiratory complications in acute PE.We retrospectively enrolled 50 consecutive
      patients hospitalized for acute PE. Plasma brain natriuretic peptide (BNP),
      troponin-I, fibrin degradation products, D-dimer, C-reactive protein, and
      arterial pH were measured to assess their prognostic significance. RVD was
      evaluated by echocardiography at admission, the clinical course during
      hospitalization was monitored for the development of complications (death,
      cardiopulmonary resuscitation, mechanical ventilation or circulatory shock), and
      the need for home oxygen therapy (HOT) was assessed at/after discharge.Thirty-two
      patients (64%) had RVD at admission, 6 (12%) developed a complicated clinical
      course, and 7 (14%) required HOT. Plasma BNP was significantly higher in patients
      with RVD (median value, 319.3 versus 50.5 pg/mL, P = 0.001). Plasma BNP was also
      significantly higher (median value, 1307.9 versus 102.6 pg/mL, P = 0.02) and
      arterial pH significantly lower (acidic) (median value, 7.371 versus 7.438, P =
      0.008) in patients who developed a complicated clinical course. In addition,
      plasma BNP was also significantly higher in patients who required HOT (median
      value, 505.1 versus 91.1 pg/mL, P = 0.02). Plasma BNP at admission is not only a
      reliable marker of RVD and predictor of short-term prognosis, but also a
      predictor of long-term respiratory prognosis in acute PE patients.

PMID- 21173519
TI  - Correlation of left ventricular pressure changes and left atrial function on
      strain rate imaging during acute left ventricular ischemia.
AB  - The objective of the present study was to evaluate whether left ventricular (LV)
      pressure changes influence left atrial (LA) function during acute LV ischemia by
      strain rate imaging. In 11 healthy dogs, the left anterior descending coronary
      artery was occluded to cause regional acute ischemia. The peak strain rate (PSR)
      values of the LA walls during the reservoir, conduit, and contractile phases of
      the LA cycle, as well as the LV pressures, were measured before and after
      ischemia. All PSR values increased significantly after ischemia (P < 0.001). Left
      ventricular end-diastolic pressure (LVEDP) increased after ischemia (P < 0.0001)
      and its percent change was positively correlated with the LA contractile phase
      and conduit phase percent changes of PSR for the anterior and lateral walls of
      the atrium (r = 0.72, 0.72, 0.83, and 0.73; P = 0.05, 0.05, 0.002, and 0.01,
      respectively). LA function is influenced by the change of LVEDP during regional
      LV ischemia. There is a compensatory increase in wall motion after regional acute
      LV ischemia.

PMID- 21173520
TI  - Atorvastatin prevents left ventricular remodeling in spontaneously hypertensive
      rats.
AB  - Statins improve left ventricular (LV) remodeling in spontaneously hypertensive
      rats (SHRs). This study was designed to investigate the effects of atorvastatin
      administered in the early stage on LV remodeling in SHRs, and to explore the
      underlying mechanisms.Sixteen male 8-week-old SHRs were randomized to receive
      distilled water (SHR-DW) or atorvastatin (SHR-ATV) for 12 weeks. Age-matched male
      Wistar-Kyoto (WKY) rats gavaged with distilled water served as controls. LV
      remodeling was evaluated, myocardial CTGF expression levels were detected using
      Western blotting, and cardiomyocyte apoptosis was detected with the TUNEL
      method.Compared with WKY and SHR-DW, atorvastatin treatment significantly
      decreased systolic blood pressure in SHRs; atorvastatin significantly inhibited
      LV remodeling, as indicated by the reduced LV weight/body weight ratio (SHR-ATV:
      4.0 +/- 0.4 versus SHR-DW: 4.7 +/- 0.4 mg/g, P < 0.05), cardiomyocyte diameter
      (SHR-ATV: 16.2 +/- 2.8 versus SHR-DW: 19.0 +/- 1.0 um, P < 0.05), and
      interstitial fibrosis (SHR-ATV: 3.3 +/- 2.1 versus SHR-DW: 4.5 +/- 1.8%, P <
      0.05). Compared with WKY, myocardial CTGF expression was significantly increased
      and cardiomyocyte apoptosis decreased in SHRs. Compared with the SHR-DW group,
      atorvastatin treatment significantly inhibited myocardial CTGF expression (SHR
      ATV: 0.69 +/- 0.21 versus SHR-DW: 1.12 +/- 0.27, P < 0.05) and induced
      cardiomyocyte apoptosis in SHRs (SHR-ATV: 5.2 +/- 0.6 versus SHR-DW: 1.9 +/-
      0.3%, P < 0.05).The results indicate that early-stage administration of
      atorvastatin effectively prevented LV remodeling in SHRs, and that inhibition of
      myocardial CTGF expression and induction of cardiomyocyte apoptosis may be the
      underlying mechanisms.

PMID- 21173521
TI  - Efficacy of renal revascularization in a patient with fibromuscular renal artery
      stenosis and heart failure.
AB  - We report the case of a 65-year-old woman with a solitary kidney who developed
      hypertension due to renal artery stenosis caused by fibromuscular dysplasia. In
      addition, an echocardiogram revealed severe left ventricular systolic and
      diastolic dysfunction. Despite antihypertensive drug treatment that included
      diuretics, her serum concentration of brain natriuretic peptide was persistently
      elevated and associated with progressive worsening of renal function. She
      underwent iliac artery to renal artery bypass grafting. After the surgery, blood
      pressure control was good, the serum concentration of brain natriuretic peptide
      decreased, and left ventricular diastolic function improved. This case
      exemplifies the efficacy of renal revascularization in patients with
      fibromuscular renal artery stenosis and heart failure.

PMID- 21173522
TI  - Lead exposure in female workers who are pregnant or of childbearing age.
AB  - In adults, high-level lead exposure often occurs in the lead-related industries.
      Acute lead poisoning has become rare, but chronic exposure to low-level lead
      remains a public health issue. With recent advances in our understanding of lead
      toxicity at low-levels, researchers have shifted their focus to studying lead at
      concentrations below those currently recommended as 'acceptable' in worker
      protection. As gender plays an important role in the storage, biokinetics, and
      toxicity of lead, it seems inappropriate to extrapolate findings of lead exposure
      in men to women. Women's bones release lead more slowly to the bloodstream, so
      blood levels remain increased for a long time after cessation of high exposure,
      reflecting the endogenous source of the lead. Particularly in pregnant women,
      bone lead release could influence health in pregnancy and be extremely harmful to
      the rapidly growing and developing fetus. Accordingly, female workers of
      childbearing age should avoid excessive lead exposure. However, because studies
      of pregnant workers encounter many difficulties and inconveniences, sufficient
      research has not been conducted in this area. As an alternative, a group of non
      occupationally exposed women, matched as well as possible for anthropometric and
      reproductive variables and with almost the same levels of blood lead, could be
      recruited for survey.

PMID- 21173523
TI  - Symptoms of intoxication in dentists associated with exposure to low levels of
      mercury.
AB  - The present study examined the effects of occupational exposure of a group of
      dentists to low levels of mercury. The study population consisted of 106 dentists
      and 94 general practitioners (referent group), from private and public clinics in
      Shiraz city. Subjects were requested to complete a questionnaire on demographic
      variables, suspicious symptoms of intoxication and work practices. Additionally,
      atmospheric and urinary concentrations of mercury were measured by Atomic
      Absorption Spectroscopy technique. The data were analysed by chi(2) test,
      independent sample t-test and multivariate logistic regression analysis, where
      applicable. Both groups were similar as far as most demographic and socioeconomic
      variables, but age and number of personal amalgam fillings, were concerned.
      Median of atmospheric concentration of mercury was found to be 3.35 MUg/m(3).
      Likewise, the urinary concentration of mercury in dentists was estimated to be
      3.16 MUg/g creatinine. This value was significantly higher than that of the
      referent group. Similarly, analysis of the data revealed that neuropsychological,
      muscular, respiratory, cardiovascular and dermal symptoms were more prevalent in
      dentists. Our findings indicate that occupational exposure of dentists to
      mercury, even at low levels, is associated with a significant increase in the
      prevalence of symptoms of intoxication.

PMID- 21173524
TI  - Exposure level and distribution characteristics of airborne bacteria and fungi in
      Seoul metropolitan subway stations.
AB  - The exposure level and distribution characteristics of airborne bacteria and
      fungi were assessed in the workers' activity areas (station office, bedroom,
      ticket office and driver's seat) and passengers' activity areas (station
      precinct, inside the passenger carriage, and platform) of the Seoul metropolitan
      subway. Among investigated areas, the levels of airborne bacteria and fungi in
      the workers' bedroom and station precincts were relatively high. No significant
      difference was found in the concentration of airborne bacteria and fungi between
      the underground and above ground activity areas of the subway. The genera
      identified in all subway activity areas with a 5% or greater detection rate were
      Staphylococcus, Micrococcus, Bacillus and Corynebacterium for airborne bacteria
      and Penicillium, Cladosporium, Chrysosporium, Aspergillus for airborne fungi.
      Staphylococcus and Micrococcus comprised over 50% of the total airborne bacteria
      and Penicillium and Cladosporium comprised over 60% of the total airborne fungi,
      thus these four genera are the predominant genera in the subway station.

PMID- 21173525
TI  - A comparison of blood lead levels between migrant and native lead workers before
      and after implementation of a new employment permit system for migrant workers.
AB  - We compared the blood lead and other lead biomarkers between migrant and native
      workers with a focus on the impact of the legal employment permit system that was
      effective from 2003, which required employers to provide mandatory annual health
      examinations for migrant workers on lead biomarkers in 1997 and 2005. The mean
      blood lead level of migrant workers was 59.5 +/- 19.4 MUg/dl, yielding 47% of
      lead poisoning cases, which was significantly higher than that of native workers
      (36.8 +/- 14.5 MUg/dl; 11% of lead poisoning cases) in 1997 before enactment of
      the act. The overall mean blood ZPP levels and ALAU of migrant workers were
      significantly higher than those of native workers. In 2005, after new migrant
      worker regulations were instituted, the mean value of above lead biomarkers
      workers was still significantly higher than that of native workers, but the
      magnitude of the differences was smaller compared with the difference in 1997. We
      confirmed that the 2003 regulations played an important role in improving the
      health of migrant workers in the lead industry in terms of their blood lead
      levels and other lead biomarkers.

PMID- 21173526
TI  - Menstrual cycle and menstrual pain problems and related risk factors among
      Japanese female workers.
AB  - Women's employment in Japan has increased substantially in recent decades,
      however little large scale research has been done on the impact of various types
      of working conditions on women's health. The aim of this study was to assess the
      menstrual cycle and menstrual pain problems of female workers and to investigate
      the factors that relate to them. The questionnaire was distributed to 8,150 women
      and 2,166 responded (26.6%). An anonymous self-administered questionnaire was
      used to get information about demographics, menstrual cycle status, the degree of
      menstrual pain, and employment and environmental factors. Irregular cycle
      menstruation was experienced in 17.1% of responded workers. We discovered the
      relationship between irregular menstrual cycles and stress, smell of cigarettes,
      age and smoking habits. Some degree of menstrual pain was experienced in 77.6% of
      responded workers. This study showed the relationship between menstrual pain and
      stress, high temperature and humidity, age, BMI, and number of births. In
      conclusion, we found that stress is thought to be an important factor related
      with menstrual cycle irregularities and menstrual pain among Japanese female
      workers.

PMID- 21173527
TI  - Exposure to respirable particulates and silica in and around the stone crushing
      units in central India.
AB  - Stone crushing unit workers suffer from particulate matters and respirable silica
      at work and in their residents nearby. The present study was undertaken to
      evaluate the area and personal exposure concentration of respirable particulate
      matters and silica in workplaces and in surrounding villages. PM(10), PM(4) and
      PM(2.5) were considered for unit area measurement and PM(4) and PM(2.5) were
      considered for personal exposure measurements. The ambient PM(10) and indoor
      respirable particulate sampling and analyses were carried out in two neighboring
      villages adjacent to a cluster of 100 stone crushing units in central India. The
      study was conducted in two years with varied seasons to provide baseline data on
      the existing particulate concentration with and without control intervention.
      Monitoring and analytical criteria were fulfilled according to the National
      Institute for Occupational safety and Health (NIOSH), USA protocol. The study
      reports the higher particulates and respirable silica with respect to the
      national and international guidelines in and around the study units. However, in
      nearby villages, the particulate concentrations and silica were comparatively
      less. An innovative dust abatement dry engineering control system was installed
      as a pilot work to reduce dust emission from the unit and the results afterward
      were found to be encouraging.

PMID- 21173528
TI  - Translocation of intratracheally instilled multiwall carbon nanotubes to lung
      associated lymph nodes in rats.
AB  - In order to assess the extrapulmonary effects of multiwall carbon nanotubes
      (MWCNT), deposition of MWCNT and histopathologic changes in lung-associated lymph
      nodes (LALN) were examined in MWCNT-administered rats. At the age of 13 wk, male
      F344 rats were intratracheally instilled with MWCNT at a dose of 0 (vehicle), 40
      or 160 MUg/rat. The rats were sacrificed on Day 1, 7, 28 or 91 after instillation
      and light microscopic examinations were performed on LALN tissues. MWCNT was
      translocated to right and left posterior mediastinal lymph nodes and parathymic
      lymph nodes. Deposition of MWCNT was greater in the posterior mediastinal lymph
      node than in the parathymic lymph node, and the amount of MWCNT deposited in
      these two lymph nodes increased gradually and dose-dependently with time. MWCNT
      was phagocytosed by nodal macrophages, and some of the MWCNT-laden macrophages
      were aggregated. Transmission electron microscopic (TEM) observation confirmed
      the presence of MWCNT fibers with a characteristic multi-walled cylindrical
      structure.

PMID- 21173529
TI  - Health, safety and environmental risk of a gas pipeline in an oil exploring area
      of Gachsaran.
AB  - The purpose of this study was assessing health, safety and environmental risk of
      a gas transfer pipeline in an oily area of Gachsaran. In this method, we used the
      Kent's pipeline risk assessment method except that to facilitate using the method
      more practically some changes were exerted into Kent's method. A pipeline with 16
      kilometers length was selected considering surrounding nature of the pipeline. It
      was divided into two sections. Analogous to Kent's method, in this method,
      parameters included: interested party's injuries, corrosion, design factor,
      incorrect operation index and consequence scoring. The difference here was that
      for consequence scoring we used ALOHA 5.6 software instead of Kent's pattern.
      Results showed that health, safety and environmental risks of section 2 (the next
      13 kilometers of outgoing pipeline from gas station after the first 3 kilometers)
      were greater. It seems the main cause of gaining a bigger risk number was related
      to more activities of interested parties around section 2. Because all figures
      gathered from indexes are almost close to gather except third parties activity.

PMID- 21173530
TI  - Comparison of physician's advice for non-specific acute low back pain in Japanese
      workers: advice to rest versus advice to stay active.
AB  - To assess the effects of physician's advice on non-specific acute low back pain
      (ALBP) in Japanese workers, existing data from a prospective, epidemiological
      study of Japanese workers were analyzed. Among workers who had had low back
      strain during the past year at baseline and responded to the 1-yr follow-up
      survey (n=475), those who obtained medical care (n=255) and received advice
      either to rest (n=68 for the rest group) or to stay active (n=32 for the active
      group) were examined. The rest group seemed to have a higher risk of ALBP than
      the active group after adjusting for age, gender, history of low back strain,
      type of physical activity at work, and severity of LBP during the past month at
      baseline (adjusted OR for the rest group vs. the active group: 3.65, 95%CI: 0.96
      13.8). Compared to the active group, low back strain was more likely to occur
      repeatedly and to become chronic in the rest group. These findings suggest that
      advice to rest may not be better than advice to stay active for preventing future
      episodes of ALBP in Japanese workers, which is consistent with previous studies
      or guidelines for the management of ALBP in Western countries.

PMID- 21173531
TI  - Influence of coffee intake on urinary hippuric acid concentration.
AB  - Intake of foods and drinks containing benzoic acid influences the urinary
      hippuric acid (HA) concentration, which is used to monitor toluene exposure in
      Japan. Therefore, it is necessary to control the intake of benzoic acid before
      urine collection. Recently, some reports have suggested that components of
      coffee, such as chlorogenic, caffeic, and quinic acids are metabolized to HA. In
      this study, we evaluated the influence of coffee intake on the urinary HA
      concentration in toluene-nonexposed workers who had controlled their benzoic acid
      intake, and investigated which components of coffee influenced the urinary HA
      concentration. We collected urine from 15 healthy men who did not handle toluene
      during working hours, after they had consumed coffee, and we measured their
      urinary HA concentrations; the benzoic acid intake was controlled in these
      participants during the study period. The levels of chlorogenic, caffeic, and
      quinic acids in coffee were analyzed by LC-MS/MS. Urinary HA concentration
      increased significantly with increasing coffee consumption. Spectrophotometric LC
      MS/MS analysis of coffee indicated that it contained chlorogenic and quinic acids
      at relatively high concentrations but did not contain benzoic acid. Our findings
      suggest that toluene exposure in coffee-consuming workers may be overestimated.

PMID- 21173532
TI  - Physiological strains of wearing aluminized and non-aluminized firefighters'
      protective clothing during exercise in radiant heat.
AB  - This study examined the influences of aluminized (Type A) and non-aluminized
      firefighters' protective clothing (Type B, C, D and CON) on physiological and
      subjective responses in radiant heat. Total clothing weight was 6.24, 6.38, 6.06,
      5.76 and 3.82 kg for Type A, B, C, D and CON, respectively. Eight firefighters
      performed exercise at an air temperature of 30 degrees C with 50%RH. Three bouts
      of 10 min-bicycle exercise in radiant heat (a globe temperature of 70 degrees C)
      was spaced by a 10 min rest with no radiant heat. Results showed that rectal
      temperature, mean skin temperature, heart rate, and body weight loss were
      significantly greater in Type A than in other types (p<0.05). For Type A, thermal
      gradient of the body reached 0.0 +/- 0.7 degrees C, heart rate showed a maximum
      level of 183 +/- 11 bpm and 1.9% of body weight was lost due to sweat secretion.
      Firefighters felt the hottest and most discomfort in Type A. It appeared that
      firefighters' thermoregulatory mechanism was severely challenged by wearing
      aluminized protective clothing during exercise in strong radiant heat. Therefore,
      it is suggested that the safe upper limits while wearing aluminized firefighters'
      clothing should be distinguished from those for typical firefighters' protective
      clothing.

PMID- 21173533
TI  - Active job, healthy job? Occupational stress and depression among hospital
      physicians in Taiwan.
AB  - This study assessed the levels and association of occupational stress and
      depression rate among physicians, and to compare physicians' occupational stress
      with that of Taiwanese employees in other occupations. The subjects were
      physicians employed at 14 participating regional hospitals in the Around Taiwan
      Health Care Alliance. Self-administered questionnaires capturing data on
      demographics, occupational characteristics, occupational stress measured using
      Job Content Questionnaire (C-JCQ), and health status measured using Taiwanese
      Depression Questionnaire (TDQ) were sent to eligible physicians. Results revealed
      that the depression rate (13.3%) was higher than that found in the general
      population (3.7%) of Taiwan. The mean scores of the JCQ dimensions "work demands"
      and "job control" were both much higher than those in most occupations in Taiwan.
      Higher depression scores were found in subjects with higher work demands, 8-10 d
      of being on duty per month, and more frequent alcohol consumption, while lower
      depression scores were found in subjects working in the east Taiwan area, with
      higher job control and with greater workplace social support. On the other hand,
      gender, smoking, and working hour were not independently correlated with
      depression, but the interaction of gender and job control also had an independent
      effect on depression. This study suggests that job stress plays an important role
      in depression in physicians; it is necessary to pay attention to physicians at
      high risk of depression, as well as their work environments, for early detection
      and intervention.

PMID- 21173534
TI  - Malignant mesothelioma: a clinical study of 238 cases.
AB  - Malignant mesothelioma is a diffuse tumor arising in the pleura, peritoneum, or
      other serosal surface and is closely associated with asbestos exposure. An
      estimated 2,500 to 3,000 cases are diagnosed each year in the United States.
      Although there are individual case reports and small series detailing the
      clinical aspects of mesothelioma, few studies examine a large series of patients
      with malignant mesothelioma from the clinical perspective. This study reports on
      the findings of 238 cases of malignant mesothelioma from a private consultative
      medical practice. Most cases had a history of occupational asbestos exposure. The
      mean latency was 48.5 yr, with women having a longer latency than men. The mean
      age at diagnosis was 70. Survival overall was poor (mean 8.8 months), but
      treatment was beneficial (mean 11.3 versus 6.4 months). Epithelioid histology
      conferred a survival advantage over sarcomatoid and responded better to
      treatment. Our data support an inverse relationship between asbestos dose and
      latency.

PMID- 21173535
TI  - Health-related quality of life and its main related factors among nurses in
      China.
AB  - The present study is to evaluate the health-related quality of life (HRQOL) and
      analyze the effect of occupational stress, job burnout and coping resource on the
      HRQOL among nurses in China. A total of 1,012 nurses were recruited from eight
      hospitals of two provinces in 2008. The Chinese version of Short Form-36 Health
      Survey and Maslach Burnout Inventory-General Survey were used to measure the
      HRQOL and burnout respectively, the Occupation Stress Inventory-Revised Edition
      was used to evaluate occupational stressor, personal strain and coping resources.
      Other potential influencing factors for HRQOL were collected using a structured
      questionnaire. HRQOL in the nurses was lower than that in the general population.
      Occupational stressor, personal strain and job burnout correlated negatively with
      the HRQOL (p<0.05) while coping resources was positively related to the HRQOL
      (p<0.05). Among the predictive factors for HRQOL, occupational stressor
      (indicated by role insufficiency and physical environment), personal strain
      (indicated by physical strain and psychological strain), job burnout (indicated
      by emotional exhaustion and professional efficacy), length of work hours (>=10 h
      per day), diet irregularity and age were the main risk factors for HRQOL, while
      recreation and self-care were the main protective factors for HRQOL. The findings
      suggest occupational stress, job burnout and coping resources play important
      roles in HRQOL in the Chinese nurses.

PMID- 21173536
TI  - Abnormal expression of 8-nitroguanine in the brain of mice exposed to arsenic
      subchronically.
AB  - To provide molecular toxicological evidences for exploring the mechanism of
      arsenic-induced neurotoxicity the accumulation of arsenic (As), the formation of
      8-nitroguanine (8-NO(2)-G) were examined in brain tissue of mice exposed to
      arsenic. And the gene expressions of inducible NOS (iNOS), superoxide dismutase 1
      (SOD1) and peroxiredoxin 2 (Prdx2) were also analyzed by GeneChip. In the result,
      the concentration of As in the brain tissue of mice was 4.00, 13.70, 21.48 and
      29.88 ng/g in the controls and experimental groups exposed to 1, 2 and 4 mg/l
      As(2)O(3), respectively and increased in dose-response manner. Nervous cells in
      the brain of mice exposed to As showed disappearances of axons, vacuolar
      degeneration in cytoplasm and karyolysis, whereas no such pathological changes
      were observed in the control group. Weak immunoreactivity against 8-NO(2)-G was
      observed in the brain tissue of mice given 1 or 2 ppm arsenic trioxide. More
      intensive immunoreactivity was found in cells at 4 ppm and it was mainly
      distributed in cytoplasm. The expressions of SOD1 and Prdx2 were down-regulated
      in the brain of mice exposed to As, but iNOS expression was not disturbed by As
      exposure. No the 8-NO(2)-G immunoreactivity or abnormal expressions of these
      genes in brain tissue were observed in controls. These results indicate that As
      induces high expression of 8-NO(2)-G in brain tissues of mice and that RNA in the
      cells may be modified by overproduced reactive nitrogen species.

PMID- 21173537
TI  - Work-related violence against security guards--who is most at risk?
AB  - Studies on violence in the work of security guards are largely lacking. This
      study is unique in that it focuses on security guards (n=1,010) in Finland, and
      assesses the different forms, prevalence, and risk factors of the work-related
      violence they often face. Information to a survey instrument was obtained by
      first interviewing 30 volunteers. Then we made a cross-sectional mailed survey
      that was sent to a randomized group of 2,000 security guards. The response rate
      was 52. We found the prevalence of verbal aggression, threats of assault, and
      physical acts against security guards at least once a month to be 39%, 19%, and
      15% respectively. As regards risk factors and who is most at risk, our results
      show that male gender, young age, low work experience, late working hours, and
      time pressure were associated with all three forms of work-related violence.
      Unlike other forms of violence, verbal aggression was highly prevalent outside
      the metropolitan area and directed towards both more and less experienced
      security guards. In prevention policies for violence, it is important to identify
      high-risk groups such as those who have less work experience.

PMID- 21173538
TI  - Main European models of workers' health protection.

PMID- 21173539
TI  - Screening of vascular calcification in hemodialysis patients.

PMID- 21173540
TI  - Influence of low-grade inflammation on plasma B-type natriuretic peptide levels.
AB  - OBJECTIVE: B-type natriuretic peptide (BNP) is a cardiac hormone. The results of
      previous in vitro studies suggest that neurohumoral factors, and not only
      hemodynamic factors, may cause BNP secretion. In this study, we examined the
      impact of serum C-reactive protein (CRP) levels on the relationship between
      echocardiographic parameters and plasma BNP levels in patients with
      cardiovascular diseases. METHODS AND PATIENTS: The study population comprised 417
      patients who visited our cardiovascular unit with a problem. Both blood sampling
      and echocardiography were performed within one month. RESULTS: Multiple
      regression analysis showed that plasma BNP levels were negatively correlated with
      male gender, body mass index, and estimated glomerular filtration rate, and
      positively correlated with serum CRP levels and left ventricular end-systolic
      dimension (LVDs). The study population was divided into two groups based on the
      75th percentile of the serum CRP levels. Single regression analysis showed that a
      regression line between LVDs and plasma BNP levels was steeper in the group of
      patients with CRP levels above the 75th percentile. Multiple regression analysis
      revealed that the interaction term (LVDs*CRP) was significant, which means LVDs
      had more impact on plasma BNP levels at higher CRP levels. CONCLUSION: Plasma BNP
      levels increased with respect to the severity of cardiac dysfunction and serum
      CRP levels, and should therefore be considered a collective or total marker for
      life-threatening conditions including systemic inflammation, and not simply as a
      marker of cardiac dysfunction in patients with cardiovascular diseases.

PMID- 21173541
TI  - Cardiovascular autonomic neuropathy studied by a laser-Doppler blood flowmeter in
      hemodialysis patients.
AB  - OBJECTIVE: Orthostatic hypotension during a hemodialysis (HD) session affects not
      only the modality but daily quality of life for HD patients because many of them
      have combined dysfunction of both sympathetic and parasympathetic nervous
      systems. Although various non-invasive methods have been applied for the
      evaluation of autonomic function, no monitor has been devised for measuring the
      dysfunction during blood purification therapy. PATIENTS AND METHODS: We evaluated
      the usefulness of laser-Doppler blood flowmeter (LDF) for measuring autonomic
      function of stable 34 regular HD patients and 24 healthy controls. The LDF device
      was applied for autonomic test by measuring periflux blood flow decreasing
      velocity (PDV) accompanied with Valsalva maneuver. We also evaluated the
      correlation between PDV and conventional tests for atherosclerosis. RESULTS: The
      average PDV (3.79+/-1.77) in HD population level was significantly lower than
      that of healthy controls (8.72+/-6.00). We also found a significant correlation
      between PDV and conventional methods such as heart rate variability and ankle
      brachial blood pressure index. CONCLUSION: Measurement of PDV by LDF is as useful
      as a conventional method for evaluating autonomic function in HD patients. The
      convenience of the device offers the benefit of daily and frequent measurement of
      autonomic dysfunction.

PMID- 21173542
TI  - 1,25-Dihydroxyvitamin D3 ameliorates podocytopenia in rats with adriamycin
      induced nephropathy.
AB  - OBJECTIVE: To investigate the role of alpha3beta1 integrin and alpha/beta
      dystroglycan in protective effects of 1,25(OH)2D3 on podocytes in rats with
      adriamycin-induced nephropathy. METHODS: Sprague-Dawley rats were randomly
      divided into three groups: control group (NC), nephropathy group (NE), and
      nephropathy+1,25(OH)2D3 group (ND). Rats in NE and ND group were injected
      intravenously with adriamycin (0.1 mg/10 g body weight) to induce nephropathy,
      and those in ND group were then subcutaneously treated with 1,25(OH)2D3 for 8
      weeks. Urinary protein level, number of urine podocytes, foot process width and
      glomerulosclerotic index were determined. Nephrin and podocin mRNA and protein
      expressions were determined by RT-PCR and western blot, respectively. Podocyte
      density and expressions of alpha3beta1 integrin and alpha/beta-dystroglycan (DG)
      were analyzed by immunohistochemistry and western blot, respectively. RESULTS:
      The increase in proteinuria, podocyturia and width of foot process in NE group
      were ameliorated after treatment with 1,25(OH)2D3 for 8 weeks. The
      glomerulosclerotic index was significantly decreased in ND group when compared
      with NE group. The podocyte density in ND group (10.3+/-1.64 cells/glomerulus)
      was significantly higher than that in NE group (8.43+/-1.75 cells/glomerulus)
      (p=0.008). 1,25(OH)2D3 treatment could significantly up-regulate the mRNA and
      protein expressions of nephrin and podocin, and the protein expressions of
      alpha3beta1 integrin and alpha/beta-DG. CONCLUSION: The expressions of nephrin,
      podocin, alpha3beta1 integrin and alpha/beta-DG were decreased in rats with
      nephropathy. However, 1,25(OH)2D3 treatment could significantly up-regulate the
      expressions of nephrin, podocin, alpha3beta1 integrin and alpha/beta-DG proteins
      which might suppress podocyte detachment and podocytopenia.

PMID- 21173543
TI  - High COPD prevalence in patients with liver disease.
AB  - OBJECTIVE: Comorbidities of chronic obstructive pulmonary disease (COPD) have
      been recognized as an important issue in COPD management. We have reported that
      patients with liver diseases show a higher prevalence of COPD, but the number of
      patients with liver diseases was small and the details of liver diseases were not
      clearly investigated. In this study, we investigated the prevalence of COPD in
      patients with liver diseases by recruiting a large number of patients, and also
      investigated was the effect of hepatitis virus infection on COPD prevalence.
      PATIENTS AND METHODS: Six hundred sixty-six patients were recruited from 9
      primary care clinics and three hospitals. All of these patients were aged 40
      years or older with chronic diseases and had not been diagnosed as having
      respiratory diseases. A spirometry was performed without administration of an
      inhaled bronchodilator. Airflow limitation was defined as FEV1/FVC<70%.
      Underlying diseases were diagnosed by doctors of the clinics or the hospitals.
      RESULTS: Two hundred fifty-six patients had liver diseases, and 410 did not. Of
      410 patients without liver diseases, 37 patients (9.0%) were diagnosed as COPD,
      and of 256 patients with liver diseases, 35 patients (13.8%) were COPD. When the
      prevalence was analyzed according to smoking, age and gender, liver diseases
      showed a significantly high odds ratio (2.10, 95%CI 1.23-3.57, p=0.006), but
      hepatitis virus infection showed a non-significant tendency toward a high odds
      ratio. CONCLUSION: The patients with liver diseases had a significantly high
      prevalence of COPD. The presence of liver disease might become a useful predictor
      for the early detection of COPD.

PMID- 21173544
TI  - Rapid screening for Japanese dysferlinopathy by fluorescent primer extension.
AB  - OBJECTIVE: Mutations in the dysferlin gene cause limb-girdle muscular dystrophy
      (LGMD) 2B and Miyoshi myopathy (MM), which are collectively named
      dysferlinopathy. Dysferlinopathy is the most frequent type of LGMD in the
      Japanese population. Molecular genetic analysis is essential for the diagnosis of
      dysferlinopathy because of its variable immunohistochemical patterns of biopsied
      muscles, including patterns similar to normal controls. The analysis of the
      entire dysferlin gene however, is time-consuming and laborious; therefore a
      simple and rapid screening method to detect hot spot mutations in the dysferlin
      gene is essential for the diagnosis of dysferlinopathy. METHODS: We previously
      showed that 4 mutations, c.937+1G>A, c.1566C>G, c.2997G>T and c.3373delG account
      for 50% of all the mutations identified in Japanese dysferlinopathy patients. We
      performed a one-tube multiplex PCR, followed by extension of primers for each
      mutation with a fluorescence-labeled dideoxynucleotide to screen the 4 hot spot
      mutations. RESULTS: The multiplex primer-extension reaction was developed on
      samples of known mutations. The extension products were represented as 4
      different peaks that corresponded to a mutated nucleotide on electropherogram.
      Using the developed screening method, we were able to detect mutations in these
      hot spots in 3 samples out of 8 clinically suspected LGMD2B/MM patients in only
      approximately 8 hours. These 3 cases were definitely diagnosed as LGMD2B/MM by
      exonic sequencing. CONCLUSION: We have developed a simple and rapid screening
      method which could facilitate the definitive diagnosis of dysferlinopathy,
      contributing to an understanding of the genotype-phenotype correlations for
      dysferlinopathy.

PMID- 21173545
TI  - A case of intravascular large B-cell lymphoma (IVLBCL) with no abnormal findings
      on chest computed tomography diagnosed by random transbronchial lung biopsy.
AB  - A 58-year-old woman was admitted with refractory fever despite receiving broad
      spectrum antibiotics. She had hypoxemia, severe anemia, elevated levels of serum
      lactic dehydrogenase and soluble interleukin-2 receptor, and a positive direct
      Coombs test, which suggested an underlying autoimmune hemolytic anemia (AIHA).
      Chest computed tomography (CT) showed no abnormal findings, but she had hypoxia,
      and her alveolar-arterial oxygen difference (A-aDO2) was increased. A random
      transbronchial lung biopsy (TBLB) was performed, and pathological analysis showed
      massive proliferation of tumor cells in the lumina of the small vessels.
      Intravascular large B-cell lymphoma (IVLBCL) was diagnosed, and her general
      status improved after chemotherapy.

PMID- 21173546
TI  - Hepatic follicular dendritic cell sarcoma favorably controlled by transcatheter
      arterial chemoembolization.
AB  - A 78-year-old woman with multiple tumors in the liver and spleen was diagnosed
      with follicular dendritic cell (FDC) sarcoma based on the histological picture of
      splenectomized specimen and its expression of CD21 and CD 23. As a paraneoplastic
      immune disorder, Coombs' test was positive although hemolysis was not obvious.
      Since systemic chemotherapies were ineffective for residual liver tumors,
      transcatheter arterial chemoembolization (TACE) was performed with subsequent
      tumor reduction. Currently, the patient is alive 27 months after the diagnosis
      with residual hepatic tumors favorably controlled by repeated TACE. Our
      experience suggests that TACE is useful for the management of hepatic FDC
      sarcoma.

PMID- 21173547
TI  - Hydropneumopericardium with metastatic lung carcinoma and pneumonia.

PMID- 21173548
TI  - Transient cytotoxic edema in the splenium of the corpus callosum.

PMID- 21173549
TI  - Roles of ATP-binding cassette transporter A7 in cholesterol homeostasis and host
      defense system.
AB  - ATP-binding cassette transporter (ABC) A7 is an ABC family protein that is a so
      called full-size ABC transporter, highly homologous to ABCA1, which mediates the
      biogenesis of high-density lipoprotein (HDL) with cellular lipid and helical
      apolipoproteins. ABCA7 mediates the formation of HDL when exogenously transfected
      and expressed; however, endogenous ABCA7 was shown to have no significant impact
      on the generation of HDL and was found to be associated with phagocytosis
      regulated by sterol regulatory element binding protein 2. Since phagocytosis is
      one of the fundamental functions of animal cells as an important responsive
      reaction to infection, injury and apoptosis, ABCA7 seems to be one of the key
      molecules linking sterol homeostasis and the host defense system. In this
      context, HDL apolipoproteins were shown to enhance phagocytosis by stabilizing
      ABCA7 against calpain-mediated degradation and increasing its activity, shedding
      light on a new aspect of the regulation of the host-defense system.

PMID- 21173550
TI  - Possible involvement of beta1 receptors in various emetogen-induced increases in
      salivary amylase activity in rats.
AB  - We investigated the inhibitory effects of beta1- or beta2-adrenoceptor (AR)
      antagonists on salivary amylase secretion produced by various emetic agents, such
      as cisplatin, apomorphine, and lithium chloride (LiCl), or the non-emetic agent
      beta(1/2)-AR agonist isoprenaline in rats. We also determined the inhibitory
      effect of metoclopramide, a dopamine D2-receptor antagonist, on increases in the
      salivary amylase activity induced by apomorphine or granisetron, a 5-HT(3)
      receptor antagonist, on LiCl-induced increased salivary amylase activity.
      Isoprenaline (0.01 mg/kg, s.c.) produced an increase in salivary amylase and the
      increase was inhibited by the beta(1/2)-AR antagonist propranolol (5 mg/kg, s.c.)
      and beta1-AR antagonist atenolol (2 mg/kg, s.c.) but not by the beta2-AR
      antagonist butoxamine (8 mg/kg, s.c.). The increased amylase activity induced by
      cisplatin (15 mg/kg, i.v.), apomorphine (3 mg/kg, s.c.), or LiCl (120 mg/kg,
      i.p.) was inhibited significantly by atenolol (2 mg/kg, s.c.) but not by
      butoxamine (8 mg/kg, s.c.). In addition, increases in amylase activities induced
      by apomorphine and LiCl were inhibited significantly by metoclopramide (10 mg/kg,
      i.v.) and granisetron (3 mg/kg, i.v.), respectively. These results suggest that
      salivary amylase secretion induced by various emetogens is involved in beta1
      adrenoceptor activity and that salivary amylase activity is useful to detect
      emetogens with no direct beta1-AR activation in rats, a species that does not
      exhibit vomiting.

PMID- 21173551
TI  - Formyl peptide receptor 1 and 2 dual agonist inhibits human neutrophil chemotaxis
      by the induction of chemoattractant receptor cross-desensitization.
AB  - Formyl peptide receptor 1 (FPR1) and FPR2/ALX are known to control neutrophil
      chemotaxis in response to various ligands. In this study, we investigated the
      inhibitory mechanism of compound 43 (Cpd43), an FPR1 and FPR2/ALX dual agonist,
      on human neutrophil chemotaxis. Precedent stimulation of human peripheral blood
      neutrophils with Cpd43 rendered the cells unresponsive in calcium mobilization
      induced by interleukin-8, C5a, or leukotriene B4. In addition, neutrophils
      pretreated with Cpd43 lost their chemotactic responses against these
      chemoattractants, wherein the expressions of chemoattractant receptors CXCR1,
      CXCR2, C5a receptor, and leukotriene B4 receptor 1 on the surface of neutrophils
      were all diminished significantly by treatment with Cpd43. By evaluating its
      pharmacological effect on 341 molecules, including receptors and enzymes, we also
      confirmed that Cpd43 has a highly specific affinity to FPR1 and FPR2/ALX and does
      not show binding affinity to the other chemoattractant receptors. These results
      indicate a previously unrecognized inhibitory mechanism of Cpd43 on neutrophil
      chemotaxis: the induction of cross-desensitization of multiple chemoattractant
      receptors in human neutrophils through its FPR1 and FPR2/ALX dual agonism.

PMID- 21173552
TI  - Associations between age of gilts at first mating and lifetime performance or
      culling risk in commercial herds.
AB  - Age of gilts at first mating (AFM) is a factor associated with reproductive
      performance of female pigs. The objectives of the present study were to compare
      AFM and reproductive performance across parity between three herd groups based on
      a productivity measurement and to determine lifetime performance by AFM and the
      herd groups. The female data included 38,212 mated gilts entered between 2001 and
      2003, and the herd data included mean measurements from 2001 to 2006 in 101
      herds. The average female inventory of the 101 herds was 370.2 females. Females
      were categorized into five groups: AFM 188-208, 209-229, 230-250, 251-271 or 272
      365 days. Three herd groups were formed on the basis of the upper and lower 25th
      percentiles of pigs weaned per mated female over six years: high-, intermediate-
      and low-performing herds. Multilevel mixed-effects models were performed to
      analyze comparisons. The AFMs (+/- SEM) in the high-, intermediate- and low
      performing herds were 239.5 +/- 0.22, 247.4 +/- 0.21 and 256.7 +/- 0.35 days,
      respectively. As the AFM increased from 209-229 to 272-365 days, annualized
      lifetime pigs born alive (PBA) decreased from 18.2 to 15.3 pigs, and the number
      of parities at removal decreased from 4.8 to 4.1 (P<0.05). In parity 1, females
      with an AFM of 209-229 days had fewer PBA, but had a lower culling risk and
      shorter weaning-to-first mating interval than those with an AFM of 251-271 days
      (P<0.05). In conclusion, we recommend management practices such as boar exposure
      to hasten puberty in gilts and decrease AFM.

PMID- 21173553
TI  - Effects of polyphenols from seed shells of Japanese horse chestnut (Aesculus
      turbinata BLUME) on methotrexate-induced intestinal injury in rats.
AB  - The purpose of this study was to evaluate the effects of polyphenols from seed
      shells of Japanese horse chestnut (JHP) on methotrexate (MTX)-induced intestinal
      injury in rats. MTX application caused intestinal morphological injury and
      increase in malondialdehyde (MDA) levels, decrease in levels of glutathione (GSH)
      and glutathione peroxidase (GSH-Px) activities in small intestine. However, oral
      administration of JHP ameliorated MTX-induced intestinal injury and inhibited the
      increase in MDA and the decrease in GSH and GSH-Px activity in small intestine.
      In conclusion, our results indicated that oral administration of JHP alleviated
      MTX-induced intestinal injury through its antioxidant properties.

PMID- 21173554
TI  - The effect of ovarian status and follicular diameter on maturational ability of
      domestic cat oocytes.
AB  - The objective of this study was to clarify the effect of ovarian status and
      follicular size on morphological normality and maturational ability of cat
      oocytes. Ovarian status was classified into inactive, follicular, luteal and
      prepubertal, and follicles were classified into three groups according to their
      diameter (400-800, 800-1200 and 1200-2000 um). In each ovarian status, the number
      of follicles decreased but the percentage of morphologically normal oocytes
      increased with the growth of follicles (p<0.05). Only a single follicle that was
      1200-2000 um in diameter was observed in two of the five prepubertal cats. In
      follicles that were 800-1200 um in diameter, the percentage of normal oocytes and
      maturation rate were higher in prepubertal cats than in mature cats (p<0.05).
      Oocyte diameter tended to increase with the growth of follicles. After oocytes
      were cultured individually in droplets of maturation medium, the oocyte
      maturation rate increased with the growth of follicles in each ovarian status
      (p<0.05). In conclusion, oocytes collected from larger follicles possess higher
      maturational ability in vitro in sexually mature cats. In prepubertal cats, a
      higher maturation rate can be obtained from oocytes derived from small follicles
      compared with in mature cats.

PMID- 21173555
TI  - [Acute lower gastrointestinal bleeding from the appendix diagnosed by
      colonoscopy].

PMID- 21173556
TI  - [Incidental gastrointestinal subepithelial mass].
AB  - Incidental gastrointestinal subepithelial mass is increasing with national cancer
      screening endoscopy. Most of gastrointestinal subepithelial mass are small-sized
      and asymptomatic tumor with benign nature, but gastrointestinal stromal tumor
      should be ruled-out because of its malignant behavior. Although conventional
      endoscopy alone can differentiate the nature of subepithelial mass, more accurate
      diagnosis can be achieved with endoscopic ultrasonography and its guided biopsy.
      In this review, differential diagnosis and treatment strategy of incidental
      gastrointestinal subepithelial mass would be presented.

PMID- 21173557
TI  - [The usefulness of Doppler sonography in the assessment of disease activity of
      ulcerative colitis].
AB  - BACKGROUND/AIMS: disease activity in ulcerative colitis (UC) is generally
      assessed using symptoms, laboratory data, endoscopic findings, and histology of
      the biopsy specimens. In this study, we compared disease activity of UC as
      determined by clinical features and endoscopic findings, and aimed to assess the
      clinical usefulness of Doppler sonography. METHODS: the duplex Doppler sonography
      of superior mesenteric artery (SMA) and inferior mesenteric artery (IMA) of 10
      patients with clinically inactive UC and 20 patients with active UC were
      evaluated by one radiologist who was blinded to clinical information. Peak
      systolic velocity (PSV), end diastolic velocity (EDV), resistance index (RI), and
      pulsatility index (PI) of the SMA and IMA were evaluated. All patients underwent
      biochemical and endoscopic evaluations thereafter. Correlation between disease
      activity by the Truelove-Witts classification and the Mayo scoring system was
      measured, and we compared hemodynamic parameters between active and inactive UC.
      RESULTS: correlation rate of disease activity between these two scoring systems
      was 93.3%. Flow velocities (PSV, p<0.001 and EDV, p=0.03) and PI (p=0.03) were
      significantly higher in patients with active UC than inactive UC. PSVs of the SMA
      and IMA were also significantly correlated with disease severity. The active UC
      could be accurately diagnosed using Doppler sonography (AUC=0.83; 95% confidence
      interval 0.68-0.99). CONCLUSIONS: in patients with UC, clinical stage was well
      matched with endoscopic disease activity. Doppler sonography was a readily
      available method, and PSV of SMA would be clinically useful in predicting of
      disease activity and severity.

PMID- 21173558
TI  - [Clinical aspects of intraabdominal cystic lymphangioma in Korea].
AB  - BACKGROUND/AIMS: cystic lymphangioma is an uncommon disease, and rarely develops
      in the intraabdomen. The aim of this article was to discuss about clinical
      characteristics of intraabdominal cystic lymphangioma developed in Korea.
      METHODS: age, sex, symptoms, locations and size of the lesions, diagnostic
      methods, treatments, complications and recurrence were analyzed in 13
      pathologically confirmed cases of intraabdominal cystic lymphangioma and 18 cases
      of literature consideration reported in Korea. RESULTS: intraabdominal cystic
      lymphangioma commonly developed in adults compared to the other lymphangioma, and
      frequently located in the mesentery. Abdominal pain was the most common symptom,
      but it was a non-specific finding. Tenderness and abdominal mass were not
      significantly associated. The size of mass was diverse. Abdominal ultrasonography
      and abdominal CT were diagnostic tools most commonly used, but preoperative
      diagnosis was possible only in 22.6%. All patients were discharged without any
      complications, and no recurrence was reported. CONCLUSIONS: preoperative
      diagnosis of intraabdominal cystic lymphangioma is difficult and symptoms and
      signs are not specific. Intraabdominal cystic lymphangioma should be suspected in
      patients with non specific abdominal pain and intraabdominal mass and active
      diagnostic evaluation is mandatory.

PMID- 21173559
TI  - [Clinical features and predictive factors of acute hepatitis A complicated with
      acute kidney injury].
AB  - BACKGROUND/AIMS: we assessed the clinical features and prognosis of acute viral
      hepatitis A (AHA) complicated with acute kidney injury (AKI) and elucidated
      predictive factors for AKI in patients with AHA. METHODS: we reviewed medical
      record of 391 patients with AHA admitted at our institution since 2000. RESULTS:
      AKI was present in 45 patients (11.5%). The proportion of the AKI group increased
      since 2008 (5.4% before 2008 vs. 15.9% since 2008, p=0.001). The AKI group was
      older than the non-AKI group (35.7+/-8.7 years vs. 31.3+/-7.8 years, p=0.002).
      Other baseline clinical characteristics were similar between two groups. Initial
      hemoglobin, platelet, and serum albumin were significantly low and prothrombin
      time, serum bilirubin, creatinine, AST, and ALT were significantly high in the
      AKI group. Hepatic encephalopathy, ascites, gastrointestinal bleeding, and sepsis
      were more frequently observed in the AKI group. While six patients (13%) in the
      AKI group received liver transplantation (LT) but three patients died within one
      month, one patient in the non-AKI group receiving LT is alive. Multivariate
      analysis showed that older age (OR 1.07, 95% CI 1.02-1.12), initial
      thrombocytopenia <150,000/mm2 (OR 2.85, 95% CI 1.24-6.57), prothrombin time (PT)
      prolongation (OR 5.34, 95% CI 2.55-11.19), and hypoalbuminemia (OR 8.24, 95% CI
      2.53-26.86) were independently associated with the occurrence of AKI.
      CONCLUSIONS: AHA with AKI is an increasing problem showing significant morbidity
      and mortality in Korea. AKI is highly associated with older age, initial
      thrombocytopenia, PT prolongation, or low serum albumin, and has bad prognostic
      effect.

PMID- 21173560
TI  - [Treatment efficacy of clevudine, entecavir and lamivudine in treatment-naive
      patients with HBeAg-positive chronic hepatitis B].
AB  - BACKGROUND/AIMS: clevudine is a potent antiviral agent that has demonstrated
      efficacy in patients with chronic hepatitis B. This study compared the efficacy
      of clevudine (C), entecavir (E) and lamivudine (L) in treatment-naive patient
      with HBeAg-positive chronic hepatitis B. METHODS: a total of 146 treatment-naive
      patients with HBeAg-positive chronic hepatitis B received clevudine, entecavir or
      lamivudine. C group (n=39) received 30 mg of clevudine, E group (n=39) received
      0.5 mg of entecavir and L group (n=68) received 100 mg of lamivudine once a day
      for more than 48 weeks. The efficacy analysis estimated the mean changes of the
      HBV DNA levels as a virologic response, the normalization of the ALT levels (less
      than 35 IU/L) as a biochemical response and loss of HBeAg or seroconversion as a
      serologic response. The serum HBV DNA level was quantified by hybrid capture and
      real-time PCR assay. RESULTS: before the administration of clevudine, entecavir
      and lamivudine, the mean HBV DNA and ALT levels and the gender and age were well
      balanced among the three groups (p>0.05). For the virologic response at 48 weeks,
      the mean changes of the HBV DNA levels from baseline of the C, E and L groups
      were -3.8+/-2.2, -4.5+/-1.9 and -2.5+/-2.1 log copies/mL. C and E group showed
      superior antiviral activity compared to that of L group (p<0.0001), but no
      significant differences in antiviral response were noted between C and E groups.
      For the biochemical response at 48 weeks, the normalization of the ALT levels
      (less than 35 IU/L) among the C, E and L groups was 82%, 74% and 71%,
      respectively (p=0.46). The rates of undetectable serum HBV DNA (less than 300
      copies/mL) of the C, E and L groups were 39%, 69% and 27%, respectively
      (p<0.0001). For the serologic response at 48 weeks, the loss of HBeAg was 13%,
      31% and 24% and the seroconversion was 10%, 23% and 17%, respectively. There was
      no difference of efficacy among the three groups regarding ALT normalization or
      serologic response (p>0.05). Viral breakthrough in C group was noted at 24 weeks
      (5%) and 48 weeks (21%), but no biochemical breakthrough was noted. The elevation
      of the serum CK level was noted in only 1 patient of group C at 48 weeks (2.56%)
      after therapy. For the patients without or with liver cirrhosis (LC), C and E
      group showed superior antiviral activity compared to that of the L group, but the
      antiviral activity was more effective in non- LC group than LC group (p<0.0001 vs
      p=0.036). CONCLUSIONS: clevudine therapy compared with lamivudine for 48 weeks
      showed significantly potent antiviral efficacy in treatment-naive patients with
      HBeAg-positive chronic hepatitis B, and especially in the non-LC patients.
      However, the antiviral efficacy of clevudine was similar to that of entecavir
      even though taking into account relatively short follow up period and
      retrospective study.

PMID- 21173561
TI  - [A case of acute necrotizing esophagitis].
AB  - Acute necrotizing esophagitis, which presents as a black esophagus on endoscopy,
      is a rare disorder. We report a case of a 48-year-old male with acute necrotizing
      esophagitis, associated with alcoholic hepatitis. He was admitted to our hospital
      because of hematemesis. On initial upper esophagogastroduodenoscopy, diffuse
      friable black colored mucosa at whole length of the esophagus was observed. After
      conservative treatment with proton-pump inhibitor, esophageal mucosal lesion was
      healed without complication.

PMID- 21173562
TI  - [A case of peritoneal mesothelioma with direct invasion to gastric mucosa].
AB  - Mesothelioma is a rare aggressive tumor arising from the mesothelial cell and
      regarded as universally fatal disease with average survival around 1 year. The
      incidence rate is varied from one to forty per million in different countries and
      increasing by the year. The most common site of tumor origin is the pleura and
      only 20% to 33% of mesothelioma arise from the peritoneum. There are increasing
      reports of malignant mesothelioma with forty to fifty fatal cases per year in
      Korea. Histological studies with immunohistochemical stain is helpful for the
      diagnosis of peritoneal mesothelioma and imaging modality alone is not sufficient
      for diagnosis, so it is difficult to confirm diagnosis. A 64-year-old male
      patient was admitted to the hospital with a palpable mass on abdomen. The 6x6 cm
      sized huge mass was seen on the body of stomach adjacent to the peritoneum. We
      report a case of malignant peritoneal mesothelioma without evident exposure to
      asbestos, of which direct invasion to the gastric mucosa was confirmed by
      endoscopic biopsy and immunohistochemical stain.

PMID- 21173563
TI  - Chronic Non-granulomatous ulcerative jejunoileitis assessed by wireless capsule
      endoscopy.
AB  - Chronic non-granulomatous jejunoileitis is a rare disease characterized by
      malabsorption, abdominal pain, and diarrhea that causes shallow ulcers in the
      small bowel. The etiology of chronic non-granulomatous jejunolieitis remains
      unknown. A 69-year-old man complained of abdominal pain and lower extremity
      edema. A 99m-Tc albumin scan showed increased radioactivity at the left upper
      quadrant, suggesting protein-losing enteropathy. A small bowel follow-through did
      not disclose any lesions. Wireless capsule endoscopy revealed several small bowel
      ulcers and strictures. A jejunoileal segmentectomy with end-to-end anastomosis
      was performed, and the histologic examination revealed non-granulomatous ulcers
      with focal villous atrophy. Ruling out all other possible diagnoses, we diagnosed
      our patient with chronic non-granulomatous ulcerative jejunoileitis.
      Postoperatively, the patient's abdominal pain and lower extremity edema improved,
      and the serum albumin normalized. This is the first case of chronic non
      granulomatous ulcerative jejunoileitis localized by wireless capsule endoscopy
      and treated successfully with segment resection.

PMID- 21173564
TI  - [A case of pseudomembranous colitis in a juvenile rheumatoid arthritis patient
      taking methotrexate].
AB  - Pseudomembranous colitis is mainly caused by antibiotics and Clostridium
      difficile infection. But conditions such as gastrointestinal surgery, antacid
      medication, anti-neoplastic agent or immunosuppressive agent which influences the
      normal flora of colon can induce colitis without the administration of any
      antibiotics. We experienced a 13 year-old male who was taking low-dose
      methotrexate for juvenile rheumatoid arthritis complained diarrhea and abdominal
      pain for 3 weeks. Sigmoidoscopic findings revealed diffuse patch yellowish
      pseudomembranes on the rectum. Histologic finding was compatible to
      pseudomembranous colitis. His symptom was improved after stop taking methotrexate
      and the administration of metronidazole. If a patient treated with
      immunosuppressive agents or antineoplastic agents complains diarrhea, fever or
      abdominal pain and has not improved with conservative care, pseudomembranous
      colitis should be taken into account as a differential diagnosis and prompt
      treatment is required for better prognosis.

PMID- 21173565
TI  - [Acute hepatitis A complicated with acute kidney injury].

PMID- 21173566
TI  - Barrier dysfunction caused by environmental proteases in the pathogenesis of
      allergic diseases.
AB  - Skin barrier dysfunction has emerged as a critical driving force in the
      initiation and exacerbation of atopic dermatitis and the "atopic march" in
      allergic diseases. The genetically determined barrier deficiency and barrier
      disruption by environmental and endogenous proteases in skin and epithelium are
      considered to increase the risk of sensitization to allergens and contribute to
      the exacerbation of allergic diseases. Sources of allergens such as mites,
      cockroaches, fungi, and pollen, produce or contain proteases, which are
      frequently themselves allergens. Staphylococcus aureus, which heavily colonizes
      the lesions of atopic dermatitis patients and is known to trigger a worsening of
      the disease, also produces extracellular proteases. Environmental proteases can
      cause barrier breakdown in the skin, not only in the epithelium, and stimulate
      various types of cells through IgE-independent mechanisms. Endogenous protease
      inhibitors control the functions of environmental and endogenous proteases. In
      this review, we focus on the barrier dysfunction caused by environmental
      proteases and roles of endogenous protease inhibitors in the pathogenesis of
      allergic diseases. Additionally, we examine the subsequent innate response to Th2
      skewed adaptive immune reactions.

PMID- 21173567
TI  - Filaggrin gene defects and the risk of developing allergic disorders.
AB  - Filaggrin is a key protein that facilitates terminal differentiation of the
      epidermis and formation of the skin barrier. Mutations in the gene encoding
      filaggrin (FLG) have been identified as the cause of ichthyosis vulgaris (IV) and
      have been shown to be major predisposing factors for atopic dermatitis (AD).
      Approximately 40 loss-of-function FLG mutations have been identified in patients
      with ichthyosis vulgaris (IV) and/or atopic dermatitis (AD) in Europe and Asia.
      Major differences exist in the spectra of FLG mutations observed between
      different ancestral groups. Notably, prevalent FLG mutations are distinct between
      European and Asian populations. Many cohort studies on FLG mutations in AD have
      revealed that approximately 25-50% of AD patients harbour filaggrin mutations as
      a predisposing factor. In addition, FLG mutations are significantly associated
      with AD-associated asthma. The risk for developing allergic rhinitis is also
      significantly higher with a FLG mutation, both with and without accompanying AD.
      Recent studies have hypothesized that skin barrier defects caused by FLG
      mutations allows allergens to penetrate the epidermis and to interact with
      antigen-presenting cells, leading to the development of atopic disorders
      including asthma. The restoration of skin barrier function seems a feasible and
      promising strategy for prophylactic treatment of AD patients with FLG mutations.

PMID- 21173568
TI  - Efficacy of epinastine hydrochloride for antigen-provoked nasal symptoms in
      subjects with orchard grass pollinosis.
AB  - BACKGROUND: Among the gramineae species, orchard grass is a typical causative
      pollen that provokes seasonal rhinitis. The purpose of this study was to examine
      the protective efficacy of epinastine hydrochloride for signs and symptoms caused
      by repeated nasal provocation with discs containing orchard grass pollen.
      METHODS: A single-dose, placebo-controlled, double-blind, crossover clinical
      study was conducted in subjects with orchard grass pollinosis. The pollen
      challenge was conducted with the use of provocation discs containing orchard
      grass pollen. RESULTS: Epinastine hydrochloride suppressed nasal symptoms caused
      by nasal provocation tests using orchard grass pollen discs. Among the nasal
      symptoms, the number of sneezing was significantly inhibited 30 minutes and 60
      minutes after the administration of epinastine hydrochloride, as compared with
      placebo. There were no adverse reactions to the study drugs. CONCLUSIONS: Our
      results suggest that nasal provocation tests with discs containing orchard grass
      pollen is a useful method for evaluating the onset of action of antiallergic
      drugs. As compared with placebo, epinastine hydrochloride decreased early-phase
      sneezing and the total nasal symptom score after repeated nasal provocations with
      orchard grass pollen discs.

PMID- 21173569
TI  - Molecular cloning and expression of Cucumisin (Cuc m 1), a subtilisin-like
      protease of Cucumis melo in Escherichia coli.
AB  - BACKGROUND: Oral allergy syndrome resulted from plant-derived foods is frequent
      among adults. Allergy to melon (cucumis melo) is one of the most frequent fruit
      allergies in Iran. Three different major allergens have been found in Cucumis
      melo that Cuc m 1 (cucumisin) has been identified as the major allergen of melon.
      Cucumisin is an alkaline serine protease that it is found as a 78kDa protein in
      precursor form. The aim of this study was production of recombinant Cuc m 1 in
      Escherichia coli (E. coli) cells and characterization of its allergenicity
      property. METHODS: Production of recombinant Cuc m 1 was carried out by cDNA
      cloning technique into the pET32b(+) vector using specific primers designed based
      on cucumisin nucleotide sequence available in Genebank database, cucumisin
      encoding gene and directional cloning method. Cloned plasmid into E. coli TOP10
      was transformed into E. coli BL21 and expression of the protein was induced by
      IPTG. The recombinant protein was purified via Ni-NTA affinity chromatography
      using histidine tag in recombinant protein. IgE binding of this protein was
      assessed by IgE-immunoblotting, ELISA and inhibition ELISA. RESULTS: The
      directional cloning was resulted in expression of a fusion Cuc m 1.
      Immunoblotting with sera of patients allergic to melon showed strong reactivity
      with purified protein band. Inhibition assays demonstrated that purified rCuc m 1
      could be the same with natural form of Cuc m 1 in total extract. CONCLUSIONS: In
      the present study, we have provided a functional recombinant cucumisin allergen,
      rCuc m 1 with 86kDa, which may be used as a standard allergen for clinical
      diagnosis and study of allergy to melon.

PMID- 21173570
TI  - Some asthmatics show elevation of the peripheral venous oxygen pressure (PvO(2)).

PMID- 21173571
TI  - Is post-transcriptional stabilization, splicing and translation of selective
      mRNAs a key to the DNA damage response?
AB  - In response to DNA damage, cells activate a complex, kinase-based signaling
      network that consist of two components--a rapid phosphorylation-driven signaling
      cascade that results in immediate inhibition of Cdk/cyclin complexes to arrest
      the cell cycle along with recruitment of repair machinery to damaged DNA,
      followed by a delayed transcriptional response that promotes cell cycle arrest
      through the induction of Cdk inhibitors, such as p21. In recent years a third
      layer of complexity has emerged that involves post-transcriptional control of
      mRNA stability, splicing, and translation as a critical part of the DNA damage
      response. Here, we describe recent work implicating DNA damage-dependent
      modification of RNA-binding proteins that are responsible for some of these mRNA
      effects, highlighting recent work on post-transcriptional regulation of the cell
      cycle checkpoint protein/apoptosis inducer Gadd45a by the checkpoint kinase
      MAPKAP Kinase-2.

PMID- 21173572
TI  - Frequent epigenetic inactivation of KIBRA, an upstream member of the
      Salvador/Warts/Hippo (SWH) tumor suppressor network, is associated with specific
      genetic event in B-cell acute lymphocytic leukemia.
AB  - The WW-domain containing protein KIBRA has recently been identified as a new
      member of the Salvador/Warts/Hippo (SWH) pathway in Drosophila and is shown to
      act as a tumor suppressor gene in Drosophila. This pathway is conserved in humans
      and members of the pathway have been shown to act as tumor suppressor genes in
      mammalian systems. We determined the methylation status of the 5' CpG island
      associated with the KIBRA gene in human cancers. In a large panel of cancer cell
      lines representing common epithelial cancers KIBRA was unmethylated. But in
      pediatric acute lymphocytic leukemia (ALL) cell lines KIBRA showed frequent
      hypermethylation and silencing of gene expression, which could be reversed by
      treatment with 5-aza-2'-deoxycytidine. In ALL patient samples KIBRA was
      methylated in 70% B-ALL but was methylated in < 20% T-ALL leukemia (p = 0.0019).
      In B-ALL KIBRA methylation was associated with ETV6/RUNX1 [t(12;21) (p13;q22)]
      chromosomal translocation (p = 0.0082) phenotype, suggesting that KIBRA may play
      an important role in t(12;21) leukemogenesis. In ALL paired samples at diagnosis
      and remission KIBRA methylation was seen in diagnostic but not in any of the
      remission samples accompanied by loss of KIBRA expression in disease state
      compared to patients in remission. Hence KIBRA methylation occurs frequently in B
      cell acute lymphocytic leukemia but not in epithelial cancers and is linked to
      specific genetic event in B-ALL.

PMID- 21173573
TI  - Regulation of KEAP1 expression by promoter methylation in malignant gliomas and
      association with patient's outcome.
AB  - In light with the view that KEAP1 loss of function may impact tumour behavior and
      modify response to chemotherapeutical agents, we sought to determine whether
      KEAP1 gene is epigenetically regulated in malignant gliomas. We developed a
      Quantitative Methylation Specific PCR (QMSP) assay to analyze 86 malignant
      gliomas and 20 normal brain tissues. The discriminatory power of the assay was
      assessed by Receiving Operating Characteristics (ROC) curve analysis. The AUC
      value of the curve was 0.823 (95%CI: 0.764-0.883) with an optimal cut off value
      of 0.133 yielding a 74% sensitivity (95%CI: 63%-82%) and an 85% specificity
      (95%CI: 64%-95%). Bisulfite sequencing analysis confirmed QMSP results and
      demonstrated a direct correlation between percentage of methylated CpGs and
      methylation levels (Spearman's Rho 0.929, P=0.003). Remarkably, a strong inverse
      correlation was observed between methylation levels and KEAP1 mRNA transcript in
      tumour tissue (Spearman's Rho -0.656 P=0.0001) and in a cell line before and
      after treatment with 5-azacytidine (P=0.003). RECPAM multivariate statistical
      analysis studying the interaction between MGMT and KEAP1 methylation in subjects
      treated with radiotherapy and temozolomide (n=70), identified three prognostic
      classes of glioma patients at different risk to progress. While simultaneous
      methylation of MGMT and KEAP1 promoters was associated with the lowest risk to
      progress, patients showing only MGMT methylation were the subgroup at the higher
      risk (HR 5.54, 95% CI 1.35-22.74). Our results further suggest that KEAP1
      expression is epigenetically regulated. In addition we demonstrated that KEAP1 is
      frequently methylated in malignant gliomas and a predictor of patient's outcome.

PMID- 21173574
TI  - Non-clustered protocadherin.
AB  - The cadherin family is classified into classical cadherins, desmosomal cadherins
      and protocadherins (PCDHs). Genomic structures distinguish between PCDHs and
      other cadherins, and between clustered and non-clustered PCDHs. The phylogenetic
      analysis with full sequences of non-clustered PCDHs enabled them to be further
      classified into three subgroups: delta1 (PCDH1, PCDH7, PCDH9, PCDH11 and PCDH20),
      delta2 (PCDH8, PCDH10, PCDH12, PCDH17, PCDH18 and PCDH19) and epsilon (PCDH15,
      PCDH16, PCDH21 and MUCDHL). epsilon-PCDH members except PCDH21 have either higher
      or lower numbers of cadherin repeats than those of other PCDHs. Non-clustered
      PCDHs are expressed predominantly in the nervous system and have spatiotemporally
      diverse expression patterns. Especially, the region-specific expressions of non
      clustered PCDHs have been observed in cortical area of early postnatal stage and
      in caudate putaman and/or hippocampal formation of mature brains, suggesting that
      non-clustered PCDHs play roles in the circuit formation and maintenance. The non
      clustered PCDHs appear to have homophilic/heterophilc cell-cell adhesion
      properties, and each member has diverse cell signaling partnership distinct from
      those of other members (PCDH7/TAF1; PCDH8/TAO2beta; PCDH10/Nap1; PCDH11/beta
      catenin; PCDH18/mDab1). Furthermore, each PCDH has several isoforms with
      differential cytoplasmic sequences, suggesting that one PCDH isoform could
      activate intracellular signaling differential from other isoforms. These facts
      suggest that non-clustered PCDHs play roles as a mediator of a regulator of other
      molecules as well as cell-cell adhesion. Furthermore, some non-clustered PCDHs
      have been considered to be involved in neuronal diseases such as autism-spectrum
      disorders, schizophrenia, and female-limited epilepsy and cognitive impairment,
      suggesting that they play multiple, tightly regulated roles in normal brain
      function. In addition, some non-clustered PCDHs have been suggested as candidate
      tumor suppressor genes in several tissues. Although molecular adhesive and
      regulatory properties of some PCDHs began to be unveiled, the endeavor to
      understand the molecular mechanism of non-clustered PCDH is still in its infancy
      and requires future study.

PMID- 21173575
TI  - Interior decoration: tropomyosin in actin dynamics and cell migration.
AB  - Cell migration and invasion requires the precise temporal and spatial
      orchestration of a variety of biological processes. Filaments of polymerized
      actin are critical players in these diverse processes, including the regulation
      of cell anchorage points (both cell-cell and cell-extracellular matrix), the
      uptake and delivery of molecules via endocytic pathways and the generation of
      force for both membrane protrusion and retraction. How the actin filaments are
      specialized for each of these discrete functions is yet to be comprehensively
      elucidated. The cytoskeletal tropomyosins are a family of actin associating
      proteins that form head-to-tail polymers which lay in the major groove of
      polymerized actin filaments. In the present review we summarize the emerging
      isoform-specific functions of tropomyosins in cell migration and invasion and
      discuss their potential roles in the specialization of actin filaments for the
      diverse cellular processes that together regulate cell migration and invasion.

PMID- 21173577
TI  - RNA remodeling by chaperones and helicases.

PMID- 21173581
TI  - Addressing the educational needs of wound care professionals.

PMID- 21173585
TI  - Did you implement the 2011 skin substitute/dermal substitute changes: coding,
      payment, and coverage?

PMID- 21173586
TI  - Buerger disease (thromboangiitis obliterans): a clinical diagnosis.
AB  - Thromboangiitis obliterans, or Buerger disease, is a debilitating vascular
      disease with a well-known pronounced link to cigarette smoking and, more
      specifically, to the nicotine component of tobacco inhalation. Buerger disease is
      an inflammatory occlusive disorder that primarily affects the medium and small
      vessels of the extremities. In the present case report, a 46-year-old man,
      nonforthcoming smoker, presented to the authors' clinic with a deep ulcer at the
      head of the second metatarsal. Evidently, although the patient continued to
      smoke, the ulcer responded to therapy but regressed. Once the history was
      elaborated, the patient stopped smoking, and the ulcer healed completely within 2
      months. Follow-up appointments proved to be unremarkable and to the authors'
      knowledge, there has not been a reoccurrence, and the patient remains tobacco
      free.

PMID- 21173576
TI  - RNA helicases: emerging roles in viral replication and the host innate response.
AB  - RNA helicases serve multiple roles at the virus-host interface. In some
      situations, RNA helicases are essential host factors to promote viral
      replication; however, in other cases they serve as a cellular sensor to trigger
      the antiviral state in response to viral infection. All family members share the
      conserved ATP-dependent catalytic core linked to different substrate recognition
      and protein-protein interaction domains. These flanking domains can be shuffled
      between different helicases to achieve functional diversity. This review
      summarizes recent studies, which have revealed two types of activity by RNA
      helicases. First, RNA helicases are catalysts of progressive RNA-protein
      rearrangements that begin at gene transcription and culminate in mRNA
      translation. Second, RNA helicases can act as a scaffold for alternative protein
      protein interactions that can defeat the antiviral state. The mounting
      fundamental understanding of RNA helicases is being used to develop selective and
      efficacious drugs against human and animal pathogens. The analysis of RNA
      helicases in virus model systems continues to provide insights into virology,
      cell biology and immunology, and has provided fresh perspective to continue
      unraveling the complexity of virus-host interactions.

PMID- 21173587
TI  - Improving the detection of pressure ulcers using the TMI ImageMed system.
AB  - OBJECTIVE: The aim of the study was to evaluate a novel infrared imaging device
      coupled with an intelligent software interface that may provide a more objective
      means of identifying anatomical sites at risk for pressure ulcer (PrU)
      development as compared with the Braden Scale for Predicting Pressure Sore Risk.
      DESIGN: Repeated-measures design. SETTING: Duke University Medical Center.
      PARTICIPANTS: One hundred patients admitted to a medical unit at risk for PrUs.
      MAIN RESULTS: Only 5 participants developed early stage PrUs (Stages I and II).
      However, the infrared imaging device not only predicted all 5 participants to be
      at risk, but also predicted the anatomical location where the ulcer would
      develop. The Braden Scale correctly identified 3 of 5 participants who developed
      PrUs. It was also determined that a temperature variance of 1.5 degrees  C was
      able to accurately predict PrU development. CONCLUSION: Infrared imaging using
      intelligent software may become a promising, objective method for identifying
      incipient PrUs and provide clinicians with specific anatomical locations for
      increased preventive interventions.

PMID- 21173588
TI  - Negative-pressure wound therapy for musculoskeletal tumor surgery.
AB  - OBJECTIVE: To evaluate the effect of negative-pressure wound therapy in
      musculoskeletal tumor surgery patients. MATERIALS AND METHODS: The authors
      analyzed the medical records of 32 patients treated at the authors' institution
      for bone and soft-tissue sarcomas and secondary wound-healing complications, from
      2005 to 2008; there were 11 men and 21 women, with a mean age of 56 years (range,
      35-72 years). RESULTS: A statistically significant difference (P = .036) was
      found regarding the length of hospitalization in the conventional wound treatment
      group, group A (mean, 25.2 days; range, 15-52 days), compared with the negative
      wound pressure therapy group, group B (mean, 16.5 days; range, 12-33 days).
      CONCLUSIONS: The use of negative-pressure wound therapy for the management of
      complicated wound healing in sarcoma patients following tumor surgery is safe and
      effective and is associated with lower overall complications rates, infection
      rate, and the need for further surgery and a lower total cost of wound-healing
      treatment.

PMID- 21173589
TI  - A matched cohort study of the risk of cancer in users of becaplermin.
AB  - BACKGROUND: Becaplermin is recombinant human platelet-derived growth factor for
      topical administration that might plausibly be related to cancer risk. Extended
      follow-up of patients from clinical trials of becaplermin compared with placebo
      identified a relative risk of cancer of 2.8 (95% confidence interval [CI], 0.6
      12.8). The authors aimed to further investigate any association between
      becaplermin use and the occurrence of cancer by following a large cohort of
      patients in a clinical practice setting. METHODS: In a cohort of insured people,
      becaplermin initiators were matched to similar people who did not initiate
      becaplermin and were followed for up to 6 years for cancer incidence (up to 9
      years for cancer mortality). Cancer incidence was identified from health
      insurance claims and validated by review of medical records. Cancer mortality was
      identified through linkage to the National Death Index. RESULTS: Among 1622
      becaplermin initiators, there were 28 confirmed cancers and 9 cancer deaths, and
      among the 2809 matched comparators, there were 43 confirmed cancers and 16 cancer
      deaths. There was no increased risk of cancer with becaplermin (hazard ratio,
      1.2; 95% CI, 0.7-1.9). Cancer mortality through 2003 was increased (rate ratio
      [RR] = 5.2; 95% CI, 1.7-17.6) among subjects with 3 or more dispensings.
      Additional follow-up through 2006 indicated no elevated cancer mortality risk
      overall (RR, 1.0; 95% CI, 0.5-2.3) and no statistically significant increase in
      the subgroup with more than 3 dispensings (RR, 2.4; 95% CI, 0.8-7.4).
      CONCLUSIONS: Becaplermin does not appear to increase the risk of cancer or cancer
      mortality.

PMID- 21173591
TI  - EHR and meaningful use checklist.

PMID- 21173593
TI  - Allogeneic transplantation of CCR5-deficient progenitor cells in a patient with
      HIV infection: an update after 3 years and the search for patient no. 2.

PMID- 21173592
TI  - Multiple independent lineages of HIV-1 persist in breast milk and plasma.
AB  - DESIGN: the origin and evolution of HIV-1 in breast milk is unclear, despite the
      continuing significance of this tissue as a transmitting compartment. To
      elucidate the evolutionary trajectory of viral populations in a transient mucosal
      compartment, longitudinal sequences of the envelope glycoprotein (gp120) region
      from plasma and breast milk spanning the first year after delivery were analyzed
      in six women infected by HIV-1 subtype C. METHODS: multiple phylogenetic
      algorithms were used to elucidate the evolutionary history and spatial structure
      of virus populations between tissues. RESULTS: overall persistent mixing of viral
      sequences between plasma and breast milk indicated that breast milk is not a
      distinct genetic viral compartment. Unexpectedly, longitudinal phylogenies showed
      multiple lineages defined by long branches that included virus from both the
      breast milk and the plasma. Plasma was unlikely the anatomical origin of the most
      recent common ancestor (MRCA) in at least three of the patients, although in
      other women, the temporal origin of the MRCA of the viral populations following
      delivery occurred well before the onset of breast milk production. CONCLUSIONS:
      these findings suggest that during pregnancy/lactation, a viral variant distinct
      from the plasma virus initially seeds the breast milk, followed by subsequent
      gene flow between the plasma and breast milk tissues. This study indicates the
      potential for reactivation or reintroduction of distinct lineages during major
      immunological disruptions during the course of natural infection.

PMID- 21173595
TI  - The $2 million bash.

PMID- 21173596
TI  - The management of open lower limb fractures: the journey from amputation to
      evidence-based reconstruction and harpsichords.

PMID- 21173597
TI  - Reconstructive surgery in limbs: the case for the orthoplastic approach.

PMID- 21173598
TI  - Orthoplastic classification systems: the good, the bad, and the ungainly.
AB  - Over the last few decades, there have been many important advances in the
      treatment of severe lower limb injuries. This article looks at a few of the more
      widely used classification systems and Injury Severity Scores to examine their
      utility in a practical setting. Gustilo and Anderson formulated their landmark
      classification system in 1976 (J Bone Joint Surg Am. 1976;58:453-458). For the
      Gustilo classification system to serve any useful purpose, it is necessary to
      include supplemental information, whenever discussing these injuries, that
      includes the mechanism and energy of the injury and the presence of any other
      concomitant injuries or comorbidities. Byrd et al (Plast Reconstr Surg.
      1985;76:719-728) recognized some of the shortcomings of the Gustilo-Anderson
      system and proposed a classification system of their own in 1985. The Byrd-Spicer
      classification is less commonly used, mainly because of a large degree of
      interobserver variability, but it includes energy and presence of devitalized
      tissue. The Predictive Salvage Index, devised in 1987, recognized the importance
      of vascular injury as a prognostic indicator and was formulated in an attempt to
      avoid not only unnecessary amputations, but also to avoid protracted attempts at
      salvage that might eventually be converted into a delayed amputation. The Mangled
      Extremity Severity Score looked at 4 variables: patient age; the presence and
      duration of shock; ischemia time; and the energy of the injury. Critics question
      the relevance of its parameters. The 7 components of the Limb Salvage Index
      include injury to an artery, deep vein, nerve, bone, skin, and muscle as well as
      warm ischemia time. However, predictive results have not been reproduced. The
      Hanover Fracture Scale was initially developed on the basis of 13 weighted
      variables to quantify risk factors for amputation and complications in high
      energy trauma to a limb. This included index bacteriology, and was weighted
      heavily toward the presence of vascular injury. Nerve Injury, Ischemia, Soft
      Tissue Injury, Skeletal Injury, Shock, and Age of Patient Score attempted to
      address criticized weaknesses of the Mangled Extremity Severity Score. These
      scores can be useful tools in the decision-making process when used cautiously,
      but should not be used as the principal means for reaching difficult decisions.

PMID- 21173601
TI  - Center for devices and radiologic health agrees to have a healthcare comment site
      in the federal register regarding banning cornstarch powder on medical gloves.

PMID- 21173602
TI  - Renal cell cancer: the unmet needs.

PMID- 21173603
TI  - Knowledge of hereditary renal cancer syndromes: a pending issue for oncologists.
AB  - Renal cell cancer (RCC) is a rare disease that accounts for 2-3% of all solid
      malignancies. Although its etiology is not known, approximately 4% of RCC occurs
      in the context of complex hereditary syndromes in which the kidney lesions are
      associated with other manifestations. Therefore, clinical suspicion is essential
      for proper diagnosis and management. In this review a practical summary to aid
      treating physicians in the identification of hereditary RCC syndromes, including
      von Hippel-Lindau syndrome, hereditary papillary RCC, Birt-Hogg-Dube syndrome,
      and hereditary leiomyomatosis RCC, is provided. Early recognition of these
      specific populations will lead to better care, correct surveillance, and, in the
      near future, to personalized treatment taking advantage of underlying genetic
      defects.

PMID- 21173604
TI  - Neoadjuvant and adjuvant strategies in renal cell carcinoma: more questions than
      answers.
AB  - The current standard treatment for early stage (I-III) renal cell cancer (RCC) is
      surgery. While the prognosis of stage I tumors is excellent, stage II and
      particularly stage III have a high risk of relapse. The adjuvant treatment of
      patients with RCC remains an area of investigation, with patient selection being
      a key aspect. There are currently two prognostic nomograms to establish the risk
      of relapse in patients with resected RCC. The results of earlier studies of
      adjuvant therapy, including the use chemotherapy and/or immunotherapy after
      nephrectomy have failed to show any benefit in the outcome of patients at risk of
      developing local recurrence or distant metastases. Two recent phase III trials
      with vaccines (autologous tumor cell vaccine and autologous tumor-derived heat
      shock protein peptide complex-96) have shown promising, albeit still preliminary,
      results. In the metastatic RCC setting, recent advances in the molecular
      understanding of oncogenic pathways have led to the development of new
      therapeutic strategies with the use of targeted therapies in the adjuvant
      setting. Neoadjuvant treatment is another treatment modality currently being
      evaluated for patients with early disease and in patients with metastatic RCC
      with inoperable primary tumors. The questions that remain unanswered include
      activity of these agents in early stages of the disease, patient selection,
      optimal start time of the adjuvant treatment, and finally, the optimal length of
      treatment.

PMID- 21173605
TI  - Non-clear cell advanced kidney cancer: is there a gold standard?
AB  - Renal cell carcinoma (RCC) accounts for approximately 3% of all new cancer
      diagnosis every year. RCC arises from the renal epithelium and represents 85% of
      all kidney tumors. According to histology, these neoplasms are divided into the
      following types: clear cell, papillary, chromophobe, oncocytoma, collecting duct,
      and unclassified. Approximately, 75% of RCCs are of the clear cell type and in
      recent years, there have been substantial advances in the understanding of its
      molecular biology leading to the development of effective treatments. However,
      there is still an area of uncertainty with regard to non-clear cell histologies.
      Scarce studies have been conducted testing different drugs in this patient
      population. Thus, most of the evidence comes from small phase II trials,
      retrospective analysis, or expanded access programs. Recent insights in the
      molecular basis of these tumors have opened a promising research field. Molecules
      targeting mammalian target of rapamycin, epidermal growth factor receptor, c-MET,
      vascular endothelial growth factor, and platelet-derived growth factor are among
      some of the promising drugs tested in this setting. This article reviews the
      mechanisms of disease on RCC and summarizes treatment options with a particular
      focus on patients with non-clear cell tumors.

PMID- 21173607
TI  - Current world literature.

PMID- 21173608
TI  - Correspondence regarding: TDP-43 proteinopathy and motor neuron disease in
      chronic traumatic encephalopathy. J Neuropathol Exp Neurol 2010:69;918-29.

PMID- 21173609
TI  - Correspondence regarding: TDP-43 proteinopathy and motor neuron disease in
      chronic traumatic encephalopathy. J Neuropathol Exp Neurol 2010:69;918-29.

PMID- 21173611
TI  - Reflections of an orthopaedic surgeon on patient care and research into the
      condition of scoliosis.

PMID- 21173612
TI  - Clinical outcomes of nitinol staples for preventing curve progression in
      idiopathic scoliosis.
AB  - SUMMARY OF BACKGROUND DATA: Although bracing for idiopathic scoliosis is
      moderately successful, its efficacy has been called into question and it carries
      associated psychosocial ramifications. In this study we report the background,
      rationale, indications, surgical techniques, and early results of vertebral body
      stapling (VBS) in patients with idiopathic scoliosis. METHODS: We reviewed the
      literature on growth modulation of the growing spine and the concepts behind the
      use of VBS as a fusionless strategy. The indications are derived from
      retrospectively reviewed patients with idiopathic scoliosis treated with VBS
      followed for a minimum of 2 years. Indications for staple use included: (a) age
      <13 years in girls and 15 in boys, (b) Risser 0 or 1 and/or 1 year of growth
      remaining on wrist radiograph, (c) coronal curve <45 degrees with minimal
      rotation and flexible to <25 degrees on a side bending radiograph, and (d)
      sagittal thoracic curve <40 degrees. RESULTS: Thoracic curves measuring <35
      degrees had a success rate of 77.7%. Curves which reached <= 20 degrees on first
      erect radiograph had a success rate of 85.7%. Thoracic curves greater than 35
      degrees were not successful and require alternative treatments. Lumbar curves
      demonstrated a success rate of 86.7%. CONCLUSIONS: Some patients with idiopathic
      scoliosis with moderate curves (25 to 45 degrees) and high risk of progression
      can be safely treated with VBS as an alternative to bracing. LEVEL OF EVIDENCE:
      Level III.

PMID- 21173613
TI  - Scoliosis "nonfusion"--a reality check.
AB  - Nonfusion growing instrumentation is currently an important aspect of early onset
      scoliosis management and newer technologies to treat scoliosis without fusion
      hold the exciting promise of a new paradigm in spinal deformity care. Some of
      these technologies such as growing constructs have a sufficient track record for
      preliminary conclusions particularly about complications. Others, such as growth
      modification devices, still have limited human experience and clinical series
      comparing them to the natural history are essential before they become a part of
      standard practice. While the ideas and basic science are exciting, quality
      studies are needed to determine their actual role in practice.

PMID- 21173614
TI  - Adolescent idiopathic scoliosis case panel discussions.
AB  - BACKGROUND: A variety of options are available when deciding on the operative
      treatment of adolescent idiopathic scoliosis (AIS). These include preoperative
      decisions, intraoperative techniques and postoperative management. METHODS: A
      case-based discussion of two AIS patients chosen by the moderator were presented
      to three expert panelists as part of the premeeting course at the 2009 Annual
      Meeting of the Pediatric Orthopaedic Society meeting. The panelists had seen the
      preoperative radiographs and clinical photos prior to the panel discussion but
      did not see the treatment approach by the moderator prior to the meeting. The
      panel discussion was recorded and the transcription was then edited to include
      comments from the audience. RESULTS: The panelists first commented on some common
      preoperative, intraoperative and postoperative strategies including the use of
      spinal cord monitoring, anchor type, use of cross links and drains. A primary
      thoracic and a primary thoracolumbar/lumbar curve were presented. The panelists
      discussed their treatment strategy for each case and comments/questions from the
      audience were addressed. The panelists then commented on similar cases they had
      prepared for the meeting. CONCLUSIONS: Planning operative treatment of AIS
      requires careful preoperative assessment of the patient's clinical deformity and
      radiographs. There is significant variation amongst expert, experienced surgeons
      when choosing the surgical approach, anchor type, fusion levels, use of cross
      links, etc. However, all panelists agree that safety is of paramount importance
      and relies on, meticulous preoperatively planning, careful intraoperative
      surgical technique, accurate intraoperative spinal cord monitoring and fastidious
      postoperative followup.

PMID- 21173615
TI  - Top theories for the etiopathogenesis of adolescent idiopathic scoliosis.
AB  - BACKGROUND: Despite considerable advances in the past few decades, there is no
      generally accepted "top theory or theories" of the etiology of adolescent
      idiopathic scoliosis (AIS). This article aims to provide an overview of the
      current main hypothetical "concepts" on the etiopathogenesis of AIS. METHODS: An
      extensive literature review on hypothetical concepts on the etiology and
      etiopathogenesis of AIS. RESULTS: Concepts of etiopathogenesis in AIS were
      summarized and highlighted under 6 subgroups: genetics factors, abnormalities in
      nervous system, abnormal skeletal growth, hormones and metabolic dysfunction,
      biomechanical factors, and environmental and life style factors. An integrative
      model on the etiopathogenesis of AIS is proposed. CONCLUSIONS: The current
      knowledge is still fragmented and many fundamental questions have remained to be
      answered. In moving forward in the perusal of further advancement of our
      understanding of the etiopathogenetic mechanisms and future evidence-based
      prevention and management of AIS, multidisciplinary and multicenter innovative
      research collaboration is imminently important and necessary. CLINICAL RELEVANCE:
      With a relatively comprehensive review on the current understanding on the
      etiology and etiopathogenesis of AIS, the article would help to stimulate further
      innovative thoughts, research, and especially collaborative research in this area
      of great interest.

PMID- 21173616
TI  - Growth and adolescent idiopathic scoliosis: when and how much?
AB  - Growth in childhood and in puberty has a major influence on the evolution of
      spinal curvature. The yearly rate of increase in standing height and sitting
      height, bone age, and Tanner signs are essential parameters. Additionally,
      biometric measurements must be repeated every six months. Puberty is a turning
      point. The pubertal diagram is characterized by two phases: the first two years
      are a phase of acceleration, and the last three years is a phase of decelaration.
      Thoracic growth is the fourth dimension of the spine. Bone age is an essential
      parameter. Risser 0 covers two third of the pubertal growth. On the acceleration
      phase, olecranon evaluation is more precise than the hand. On the deceleration
      phase, the Risser sign must be completed by the hand maturation. A 30 degree
      curve at the very beginning of puberty has 100% risk of surgery. Any spinal, if
      progression is greater than 10 degree per year on the first two years of puberty
      the surgical risk is 100%.

PMID- 21173617
TI  - Seeing the spine in 3D: how will it change what we do?
AB  - BACKGROUND: The Scoliosis Research Society (SRS) has appointed a committee to
      evaluate the clinical relevance and impact of 3D analysis on scoliotic
      deformities and to develop a 3D classification of adolescent idiopathic scoliosis
      (AIS). The goal of this article is to summarize and present the work done in
      recent years within this committee and show how 3D analysis of AIS has the
      potential to change our current methods to analyse and treat scoliosis. METHODS:
      A database of 600 3D reconstructions of the spine of patients with AIS has been
      established using calibrated PA and lateral radiographs obtained from either
      digital radiographs or the EOS system. The 3D reconstructions were done using
      dedicated software and analyzed with the "da Vinci" view, a schematic top view
      representation of the 3D reconstructions, which summarizes the position of the
      End-Apex-End vertebrae planes (planes of maximum curvature). RESULTS: Preliminary
      work was done using 3D reconstructions in 409 patients with AIS. Fuzzy clustering
      techniques were used to show that the cohort could be segmented in 5 easily
      differentiated curve patterns similar to those of the Lenke and King
      classifications. Two subsequent articles have shown that 3D reconstructions can
      be divided in different groups based on the location of the plane of maximum
      curvature of their curves. One study of 66 cases has shown a consistent loss of
      kyphosis within the 5 thoracic apical vertebrae. Finally, a study of 172 Lenke 1
      curves analyzed by ISO Data cluster analysis has confirmed the presence of 2
      statistically different subtypes according to the planes passing through the End
      Apex-End vertebrae of the main thoracic curve. CONCLUSIONS: The study presented
      suggests that a valid and clinically useful 3D classification of AIS is within
      reach. 3D analysis has the potential to improve our comprehension of AIS curve
      types and automatic 3D classification may help decrease the known variability of
      current 2D classifications. LEVEL OF EVIDENCE: Level III, systematic review of
      retrospective comparative studies.

PMID- 21173618
TI  - Update on prognostic genetic testing in adolescent idiopathic scoliosis (AIS).
AB  - Case-control genome-wide association studies using a large, geographically
      diverse data base has been used to identify single nucleotide polymorphisms that
      have prognostic utility in predicting progression of mild adolescent idiopathic
      scoliosis in White patients. The calculated risk of progression score allows
      stratification of patients that can make medical care evidence based, less
      costly, and more efficient.

PMID- 21173619
TI  - Idiopathic scoliosis: cracking the genetic code and what does it mean?
AB  - Idiopathic scoliosis is one of the most common complex genetic disorders of the
      musculoskeletal system. The clinical parameters relating to onset, curve
      progression, and severity in relation to clinical prognosis and current treatment
      modalities have been defined, but do not address the cause of this disorder. In
      an effort to define causative genetic elements, multiple studies have delineated
      potential genetic loci that are statistically related to idiopathic scoliosis in
      a variety of populations. The question remains how future genetic testing and
      genomic profiling may be of aid in the therapeutic algorithms related to this
      disorder.

PMID- 21173620
TI  - Bracing for adolescent idiopathic scoliosis in practice today.
AB  - BACKGROUND: The use of orthoses in adolescent idiopathic scoliosis has a long
      history. The purpose of this article is to summarize the current practice of
      bracing in the treatment of adolescent idiopathic scoliosis. METHODS: The
      literature from the past 25 years was reviewed for primary papers that contained
      accepted inclusion criteria for bracing, meta-analyses, and summaries of existing
      opinion. Recent literature was also reviewed for current bracing practices.
      RESULTS: The highest level of existing evidence comes from a prospective center
      randomized study by Nachemson et al, which showed that bracing was effective for
      single curves of 25 to 35 degrees in female patients with a starting Risser score
      of 0 to 2. Two other studies with meta-analyses came to opposite conclusions
      because of variations in the examined investigations. Although there are few
      studies that compare different types of treatment, most show an improved outcome
      versus historical controls. The yearly number of peer-reviewed papers on the
      topic has increased markedly over this time. Two prospective randomized
      multicenter trials are underway. Reviews suggest that most orthopaedic
      specialists recommend bracing but that they differ on expected results. There is
      also a proliferation of interest in bracing by nonorthopaedists, with more varied
      indications. There are many types of full-time and part-time braces, and their
      designs and indications are described. CONCLUSIONS: Brace treatment for
      adolescent idiopathic scoliosis continues to be frequently used, and the number
      of brace types has increased. Predicting progressive curves and refining
      indications requires additional investigation.

PMID- 21173621
TI  - Adolescent idiopathic scoliosis: 5-year to 20-year evidence-based surgical
      results.
AB  - Surgical intervention for adolescent idiopathic scoliosis (AIS) should be proven
      to alter the natural history without introducing iatrogenic complications. The
      risks of surgery should be substantiated by a body of scientific research, which
      should show a clear superiority of surgery over observation, both in the short
      term and the long term. The purpose of this review was to conduct a systematic
      search of the literature to critically evaluate the scientific evidence on the
      long-term outcomes and complications of surgical intervention for AIS. Our search
      identified 39 distinct patient populations with a minimum average follow-up of 5
      years. No long-term, prospective controlled studies exist to support the
      hypothesis that surgical intervention for AIS is superior to natural history.
      Although surgery reliably arrests the progression of deformity, achieves
      permanent correction, and improves appearance, there is no medical necessity for
      surgery based on the current body of literature. However, the surgeon must not
      underestimate the psychological indication that occurs when a patient is no
      longer able to cope with the deformity.

PMID- 21173622
TI  - Lowest instrumented vertebra selection in AIS.
AB  - Appropriate selection of the lowest instrumented vertebra (LIV) is crucial to
      ensure positive outcomes after surgical management of patients with adolescent
      idiopathic scoliosis. Failure to do so can lead to curve decompensation and
      "adding on" of additional vertebrae to the deformity. Correct identification of
      the stable, end, and neutral vertebra, whether the curve(s) is structural or
      nonstructural, and classifying the type of curve are essential aspects of
      preoperative planning. Evaluating curve flexibility using fulcrum, side bending,
      push-prone, and traction can be used to predict the amount of observed
      postoperative correction for both fused and unfused curves. In addition, these
      measures can be used to foresee potential residual LIV-tilt and disc wedging
      postoperatively. Intraoperative techniques such as fine tuning, derotation, wide
      release, and in situ contouring and instrumentation type used all influence the
      LIV selection and therefore, must be taken into account preoperatively. Surgical
      goals when treating adolescent idiopathic scoliosis include achieving a well
      balanced spine in all planes while working to preserve segments and therefore,
      maintain mobility.

PMID- 21173623
TI  - "Does the outcome of adolescent idiopathic scoliosis surgery justify the rising
      cost of the procedures?".
AB  - BACKGROUND: As the cost of medical care has steady risen, patients, insurance
      companies, and the government, have all appropriately questioned the benefit of
      the care provided versus the cost. Expensive treatments such as surgery for
      spinal deformity have been especially scrutinized. This article reviews the
      history of spinal implant usage in deformity surgery, including the benefits of
      these implants to the patient and also the associated costs. The paper was
      presented at the One Day Course during the 2009 Pediatric Orthopaedic Society of
      North America annual meeting in Boston. METHODS: A review was conducted regarding
      the benefits and costs of the care provided to patients as spinal implants became
      more clinically effective. RESULTS: Compared with postoperative casting, spinal
      implants provide better deformity correction and better stability of the fusion
      mass with resulting lower rates of secondary surgery, mostly because of fewer
      pseudarthoses. Many of these advantages were achieved with the less-expensive
      second and third-generation implants. Unfortunately, patient outcomes when the
      latest, most expensive implants are used are not significantly different from
      outcomes when older, less-expensive implants are used. CONCLUSIONS: Although the
      cost of spinal deformity surgery has risen the benefit to the patient from modern
      spinal implants has also increased. Nevertheless, patient outcomes have not
      improved in proportion to the increase in costs. Outcomes from the newest, all
      pedicle screw constructs are not significantly better than outcomes from the
      older, less-expensive hybrid constructs. Rising expenses and dramatic variation
      in the cost of the same implant have led payors, hospitals, and the government to
      question the value added to the care of the patient. Some implant costs should
      fall as hospitals use competitive bidding. Surgeons should help their hospitals
      in the competitive bidding process and declare a willingness to switch to an
      equivalent system if price differences are excessive. LEVELS OF EVIDENCE: Level
      IV Economic Analysis.

PMID- 21173624
TI  - Hooks and wires--tried and true plus how to: POSNA1-DayCourse, April 29, 2009.
AB  - Fixation of the scoliotic spine can be achieved through the use of hooks and
      wires. These "tried and true" forms of fixation are discussed less commonly in
      the current era of focus on pedicle screw fixation. Sublaminar wires are still
      commonly used for neuromuscular scoliosis, in unusual curves, and at the apices
      of moderate curves. With careful attention to the technique, sublaminar wires can
      be safe and versatile. Hook fixation is generally expedient and safe. Both types
      of fixation are considerably less expensive than pedicle screws. Technical pearls
      and pitfalls are reviewed.

PMID- 21173625
TI  - The role of posterior spinal osteotomies in pediatric spinal deformity surgery:
      indications and operative technique.
AB  - The primary goals of spinal deformity surgery are to prevent the progression of
      further deformity and to improve sagittal and coronal balance. Although
      increasingly powerful instrumentation has greatly facilitated these treatment
      goals, osteotomy of the spine is sometimes necessary to address more significant
      deformity. This review provides a detailed overview of posterior spinal
      osteotomies, which have gained increased attention as an adjunct to the treatment
      of complex pediatric spine deformity. The indications, operative technique, and
      advantages and disadvantages of the Smith-Petersen, pedicle subtraction and
      vertebral column resection osteotomies will be discussed, as well as operative
      considerations generally applicable to spinal deformity surgery involving
      correction with osteotomies.

PMID- 21173626
TI  - Adolescent idiopathic scoliosis: should 100% correction be the goal?
AB  - INTRODUCTION: What constitutes optimal thoracic curve scoliosis correction is
      controversial. The development and application of powerful pedicle screw-aided
      instrumentation constructs has, in some cases, led to hypercorrection of the
      thoracic scoliosis with resulting coronal imbalance, trunk shift, and shoulder
      imbalance. The purpose of this study was to compare the clinical and radiographic
      outcomes between Lenke 1 patients with the highest and lowest degree of
      correction to assess this risk. Our hypothesis was that greater scoliosis curve
      correction can be done without producing secondary decompensation. METHODS: Using
      a prospective AIS database, Lenke 1 curves, with 2-year follow-up (n=385) were
      ranked by percent coronal correction. The top 15% or high correction group (>80%
      coronal correction) were compared with the bottom 15% or low correction group (<
      40% coronal correction). Clinical and radiographic outcomes, including parameters
      of coronal and sagittal balance, were compared using ANOVA and chi tests (P <=
      0.007). RESULTS: The high correction group (n=39) and the low correction group
      (n=40) did not differ preoperatively except in lumbar flexibility. In the coronal
      plane, the high correction group did not show postoperative clinical imbalance
      (trunk shift and shoulder height) and had better radiographic balance (C7-CSVL
      shift). The deformity-flexibility quotient (DFQ), which is the ratio of residual
      lumbar curve to remaining unfused lumbar segments, was lower (optimal) in the
      high correction group. The residual rib hump was also better. In the sagittal
      plane, the high correction group had less kyphosis secondary to a loss of
      kyphosis compared with a gain (improvement) in the low correction group. Despite
      these differences, SRS scores were not different. CONCLUSIONS: Maximizing Lenke 1
      curve correction to achieve greater lumbar correction and improved clinical
      appearance can be done without compromising coronal balance but may occur at the
      expense of sagittal alignment. However, surgeons who are learning to apply
      powerful new corrective methods should be cautious in trying to obtain full
      correction. Proper preoperative evaluation, fusion level selection, and surgical
      technique are needed to attain this outcome.

PMID- 21173629
TI  - Avascular necrosis of the femoral head.

PMID- 21173627
TI  - Nonfusion treatment of adolescent idiopathic scoliosis by growth modulation and
      remodeling.
AB  - BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a common disorder in which
      the spine gradually develops a curvature that is first detected in patients
      between 11 and 17 years of age. The only accepted treatment methods are bracing
      and surgery. Whether brace treatment alters the natural history is being
      questioned, and patient compliance is low. Surgery usually includes a spinal
      fusion that creates a rigid spine and concentrates stresses at the ends. METHODS:
      This study focuses on correlating the laboratory results with clinical reports
      for treating patients with AIS. In the laboratory, scoliosis with vertebral
      wedging has been created by asymmetric mechanical loading and has been corrected
      by reversing the loading. In the clinic, bracing and derotational casting have
      been successful in some reports, but compliance has been a problem with bracing
      and derotational casts have mainly been used in young children. Operative
      treatment has been successful, but a nonfusion operation remains elusive.
      FINDINGS AND RESULTS: In the laboratory, axial loading of growth plates altered
      growth according to the Hueter-Volkmann law, which states that compression
      decreases and distraction increases growth. Asymmetric loading of the spine
      caused asymmetric growth resulting in scoliosis with vertebral wedging.
      Asymmetric loading of tail vertebrae created vertebral wedging according to
      Wolff's law, which states that the bone remodels over time in response to
      prevailing mechanical demands. In the clinic, studies have shown that bracing may
      work if patients wore the brace as prescribed. Derotational casting in young
      children has been shown to prevent progression and even correct the scoliosis in
      some patients. Convex vertebral stapling has been successful in mild curves, but
      the results in larger curves have been disappointing. Anterolateral tethering has
      been successful in mild curves in young patients, but there is limited experience
      with this technique in patients with large curves. CONCLUSIONS: A brace that
      applies the appropriate loading and is worn as prescribed may dramatically
      improve the results of brace treatment. A procedure using external fixation or
      adjustable anterolateral tethering may achieve a nonfusion correction of AIS.
      LEVEL OF EVIDENCE: Level II.

PMID- 21173630
TI  - Denosumab (Prolia): A new option in the treatment of osteoporosis.

PMID- 21173631
TI  - BNP and heart failure: What is the connection?

PMID- 21173632
TI  - Electronic health records 101.

PMID- 21173633
TI  - Guide to care for patients. Vaginitis.

PMID- 21173638
TI  - Defining risk in women with polycystic ovary syndrome: a need for constant
      vigilance.

PMID- 21173639
TI  - Postpartum hemorrhage: becoming more evidence-based.

PMID- 21173640
TI  - Polycystic ovary syndrome and risk for long-term diabetes and dyslipidemia.
AB  - OBJECTIVE: To estimate whether women aged 20-32 years who fulfilled National
      Institutes of Health criteria for polycystic ovary syndrome (PCOS) would be at
      higher risk for subsequent development of incident diabetes, dyslipidemia, and
      hypertension, and to estimate whether normal-weight women with PCOS would have
      the same degree of cardiovascular risk as overweight women with PCOS. METHODS: We
      estimated the association of PCOS with incident diabetes, dyslipidemia, and
      hypertension over a period of 18 years among 1,127 white and African-American
      women in the Coronary Artery Risk Development in Young Adults cohort. We
      classified women at baseline (ages 20-32 years) based on self-reported symptoms
      and serum androgen measures using National Institutes of Health PCOS criteria. We
      estimated the association of PCOS and subsequent cardiovascular risk factors,
      independent of baseline body mass index (BMI), using multivariable logistic
      regression. Additionally, among 746 women with a second assessment of PCOS at
      ages 34-46 years, we estimated the association of persistent PCOS with
      cardiovascular risk factors. RESULTS: Of 1,127 women, 53 (4.7%) met criteria for
      PCOS at ages 20-32 years. Polycystic ovary syndrome was associated with a twofold
      higher odds of incident diabetes (23.1% compared with 13.1%, adjusted odds ratio
      [AOR] 2.4, confidence interval [CI] 1.2-4.9) and dyslipidemia (41.9% compared
      with 27.7%, AOR 1.9, CI 1.0-3.6) over the course of 18 years; the association
      with incident hypertension was not significant (26.9% compared with 26.3%, AOR
      1.7, CI 0.8-3.3). Normal-weight women with PCOS (n=31) had a threefold higher
      odds of incident diabetes compared with normal-weight women without PCOS (AOR
      3.1, CI 1.2-8.0). Compared with those without PCOS, women with persistent PCOS
      (n=11) had the highest odds of diabetes (AOR 7.2, CI 1.1-46.5). CONCLUSION:
      Polycystic ovary syndrome is associated with subsequent incident diabetes and
      dyslipidemia, independent of BMI. Diabetes risk may be greatest for women with
      persistent PCOS symptoms. LEVEL OF EVIDENCE: II.

PMID- 21173641
TI  - Postpartum hemorrhage resulting from uterine atony after vaginal delivery:
      factors associated with severity.
AB  - OBJECTIVE: To identify factors associated with severity of postpartum hemorrhage
      among characteristics of women and their delivery, the components of initial
      postpartum hemorrhage management, and the organizational characteristics of
      maternity units. METHODS: This population-based cohort study included women with
      postpartum hemorrhage due to uterine atony after vaginal delivery in 106 French
      hospitals between December 2004 and November 2006 (N=4,550). Severe postpartum
      hemorrhage was defined by a peripartum change in hemoglobin of 4 g/dL or more. A
      multivariable logistic model was used to identify factors independently
      associated with postpartum hemorrhage severity. RESULTS: Severe postpartum
      hemorrhage occurred in 952 women (20.9%). In women with postpartum hemorrhage,
      factors independently associated with severity were: primiparity; previous
      postpartum hemorrhage; previous cesarean delivery; cervical ripening; prolonged
      labor; and episiotomy; and delay in initial care for postpartum hemorrhage. Also
      associated with severity was 1) administration of oxytocin more than 10 minutes
      after postpartum hemorrhage diagnosis: 10-20 minutes after, proportion with
      severe postpartum hemorrhage 24.6% compared with 20.5%, adjusted OR 1.38, 95% CI
      1.03-1.85; more than 20 minutes after, 31.8% compared with 20.5%, adjusted OR
      1.86, CI 1.45-2.38; 2) manual examination of the uterine cavity more than 20
      minutes after (proportion with severe postpartum hemorrhage 28.2% versus 20.7%,
      adjusted OR 1.83, 95% CI 1.42-2.35); 3) call for additional assistance more than
      10 minutes after (proportion with severe postpartum hemorrhage 29.8% versus
      24.8%, adjusted OR 1.61, 95% CI 1.23-2.12 for an obstetrician, and 35.1% compared
      with 29.9%, adjusted OR 1.51, 95% CI 1.14-2.00 for an anesthesiologist); 4) and
      delivery in a public non-university hospital. Epidural analgesia was found to be
      a protective factor against severe blood loss in women with postpartum
      hemorrhage. CONCLUSION: Aspects of labor, delivery, and their management; delay
      in initial care; and place of delivery are independent risk factors for severe
      blood loss in women with postpartum hemorrhage caused by atony. LEVEL OF
      EVIDENCE: II.

PMID- 21173643
TI  - Women's knowledge about intrauterine contraception.
AB  - OBJECTIVES: To survey knowledge and attitudes about intrauterine contraception
      among reproductive-aged women in the area of Saint Louis, Missouri. METHODS: We
      mailed an eight-page written survey to 12,500 randomly selected households in the
      St. Louis area that asked English-literate, reproductive-aged, adult women to
      respond. The survey asked about obstetric and contraceptive history and
      effectiveness of contraceptive methods, as well as appropriate candidates for,
      side effects of, and perceived risks of intrauterine contraception. The results
      from 1,665 (13.3%) returned surveys were weighted for the analysis, which
      included descriptive statistics and polynomial logistic regression. RESULTS:
      Almost 8% of respondents were currently using or had previously used intrauterine
      contraception, and use was higher in women who reported discussing the method
      with their health care provider (adjusted odds ratio [OR] 13.4, 95% confidence
      interval [CI] 6.5-27.8). Sixty-one percent of respondents underestimated the
      effectiveness of intrauterine contraception, and up to one half of survey
      respondents were unable to correctly answer knowledge questions about
      intrauterine contraception use and safety. An additional 11%-36% of respondents
      indicated concern that intrauterine contraception is associated with
      complications such as infection, infertility, and cancer. Current and past
      intrauterine contraception users were more likely to be knowledgeable about
      intrauterine contraception. Women who were currently using intrauterine
      contraception were more likely to correctly estimate the effectiveness of
      intrauterine contraception (adjusted OR 7.6, 95% CI 3.2-18.0). CONCLUSION:
      Reproductive-aged women's specific knowledge of the benefits and risks of
      intrauterine contraception is limited. More educational interventions are needed
      to increase women's knowledge about the effectiveness and benefits of
      intrauterine contraception. LEVEL OF EVIDENCE: II.

PMID- 21173644
TI  - The effects of decidual injury on the invasion potential of trophoblastic cells.
AB  - OBJECTIVE: To investigate the effect of a decidual incision on trophoblastic
      invasion potential in vitro. METHODS: Human trophoblast cells were obtained from
      first-trimester legal terminations of pregnancy. Decidual tissue was retrieved
      from healthy, low-risk women who underwent an elective cesarean delivery at term.
      Each dissected decidual sample was divided into four similar-sized samples. The
      first slice was not treated, the second was incised with a surgical blade to
      mimic an in vivo injury, the third was incised and immediately repaired with
      medical adhesive material. This model was used to investigate trophoblastic
      invasion through a fully repaired decidua. The fourth slice was covered with
      medical adhesive material only, to exclude any effect of the adhesive material on
      the decidua. The percent of invasion was calculated as: absorbance of invaded
      cell*100=invasion index (%). Invasion was expressed as invasion index. The mean
      and standard deviation of the invasion index were then calculated. RESULTS: Eight
      decidual samples were retrieved from eight women. Incised decidua showed a
      significantly higher mean invasion index (83.3% [+/-8.1%], P=.012) than the other
      three models (intact decidua, 69.9% [+/-5.1%]; incised decidua repaired with
      adhesive, 66.6% [+/-8.2%]; intact decidua with adhesive, 58.3% [+/-11.3%]. There
      was no significant difference in the invasion index between the other models
      (P=.4). CONCLUSION: Induced decidual injury significantly increased the invasion
      potential of trophoblastic cells compared with intact decidua. Complete re
      approximation of the incised edges reversed this effect in vitro.

PMID- 21173642
TI  - Effect of injectable and oral contraceptives on glucose and insulin levels.
AB  - OBJECTIVE: To estimate the effect of using two methods of hormonal contraceptives
      (depot medroxyprogesterone acetate) or an oral contraceptive pill (OCP)
      containing 20 micrograms ethinyl estradiol and 0.15 mg desogestrel) on serum
      glucose and insulin levels, as well as predictors of any observed changes.
      METHODS: Fasting glucose and insulin levels were measured on 703 white, African
      American, and Hispanic women using depot medroxyprogesterone acetate, OCPs, or
      nonhormonal birth control at baseline and every 6 months thereafter for 3 years.
      Participants also completed questionnaires containing demographic and behavioral
      measures every 6 months. Mixed-model regression analyses were used to estimate
      changes over time in glucose and insulin levels by method, along with their
      predictors. RESULTS: Depot medroxyprogesterone acetate, but not OCP, users
      experienced slightly greater increases in glucose and insulin as compared with
      nonhormonal users (P<.001). Among depot medroxyprogesterone acetate users, a
      small but steady increase in serum glucose levels (2 mg/dL at 6 months to 3 mg/dL
      at 30 months) was observed throughout the first 30 months, but it leveled off
      after that. In contrast, serum insulin levels showed an upward (3 units at 6
      months to 4 units at 18 months) trend for the first 18 months of depot
      medroxyprogesterone acetate use and then remained almost flat thereafter.
      Elevation of insulin and glucose levels was slightly more pronounced in obese and
      overweight depot medroxyprogesterone acetate users than those who were normal
      weight. CONCLUSION: Use of depot medroxyprogesterone acetate, but not very-low
      dose OCPs containing desogestrel, can lead to slightly higher fasting glucose and
      insulin levels. LEVEL OF EVIDENCE: II.

PMID- 21173645
TI  - Gaps in diabetes screening during pregnancy and postpartum.
AB  - OBJECTIVE: To estimate the screening rate and prevalence of gestational diabetes
      mellitus (GDM) and the screening rate and prevalence of postpartum diabetes, in a
      large, national sample of pregnant women. We also estimated the potential effects
      of the new International Association of Diabetes and Pregnancy Study Groups
      recommendations, which replace the 100-g oral glucose tolerance test (OGTT) with
      the 75-g OGTT, on GDM prevalence and gestational plasma glucose testing
      practices. METHODS: We identified pregnant women who used the laboratory services
      of Quest Diagnostics and who were screened for GDM and were tested postpartum.
      Gestational diabetes mellitus prevalence was calculated according to the current
      American Diabetes Association/ Carpenter-Coustan criteria, and the new
      International Association of Diabetes and Pregnancy Study Groups criteria.
      RESULTS: Sixty-eight percent (632,820/924,873) of pregnant women aged 25 to 40
      (ie, those not in a low-risk age group) who utilized the services of Quest
      Diagnostics during this study were screened for GDM. Of the entire adult pregnant
      population (ages 18-40) who received GDM screening, 5% (40,955/842,993) had
      positive test results under the current criteria. Nineteen percent (4,486/23,299)
      of those with GDM received postpartum diabetes testing within a 6-month period.
      Ninety percent (148,749/166,085) of all confirmatory GDM tests performed on
      pregnant women at Quest Diagnostics were the 100-g OGTT. The number of women with
      GDM after receiving the 75-g OGTT would have doubled under the International
      Association of Diabetes and Pregnancy Study Groups criteria. CONCLUSION: Many
      women may not be receiving GDM screening during pregnancy. Postpartum diabetes
      screening rates after pregnancy remain low. Adoption of the new International
      Association of Diabetes and Pregnancy Study Groups criteria would require a
      significant change in current clinical practice. LEVEL OF EVIDENCE: III.

PMID- 21173646
TI  - Anesthesia-related maternal mortality in the United States: 1979-2002.
AB  - OBJECTIVE: To examine 12 years of anesthesia-related maternal deaths from 1991 to
      2002 and compare them with data from 1979 to 1990, to estimate trends in
      anesthesia-related maternal mortality over time, and to compare the risks of
      general and regional anesthesia during cesarean delivery. METHODS: The authors
      reviewed anesthesia-related maternal deaths that occurred from 1991 to 2002. Type
      of anesthesia involved, mode of delivery, and cause of death were determined.
      Pregnancy-related mortality ratios, defined as pregnancy-related deaths due to
      anesthesia per million live births were calculated. Case fatality rates were
      estimated by applying a national estimate of the proportion of regional and
      general anesthetics to the national cesarean delivery rate. RESULTS: Eighty-six
      pregnancy-related deaths were associated with complications of anesthesia, or
      1.6% of total pregnancy-related deaths. Pregnancy-related mortality ratios for
      deaths related to anesthesia is 1.2 per million live births for 1991-2002, a
      decrease of 59% from 1979-1990. Deaths mostly occurred among younger women, but
      the percentage of deaths among women aged 35-39 years increased substantially.
      Delivery method could not be determined in 14%, but the remaining 86% were
      undergoing cesarean delivery. Case-fatality rates for general anesthesia were
      16.8 per million in 1991-1996 and 6.5 per million in 1997-2002, and for regional
      anesthesia were 2.5 and 3.8 per million, respectively. The resulting risk ratio
      between the two techniques for 1997-2002 was 1.7 (confidence interval 0.6-4.6,
      P=.2). CONCLUSION: Anesthetic-related maternal mortality decreased nearly 60%
      when data from 1979-1990 were compared with data from 1991-2002. Although case
      fatality rates for general anesthesia are falling, rates for regional anesthesia
      are rising. LEVEL OF EVIDENCE: II.

PMID- 21173648
TI  - Fetal ventricular shortening fraction in hydrops fetalis.
AB  - OBJECTIVE: To estimate fetal ventricular shortening fraction, representing
      cardiac contractility, derived from cardiospatiotemporal image correlation with M
      mode display "STIC-M" in fetuses with hydrops fetalis secondary to high-output
      (fetal anemia) and low-output causes (congenital heart defects). METHODS: A cross
      sectional study was conducted in normal fetuses (group 1), fetuses with
      hemoglobin Bart's disease with (group 2) and without (group 3) hydrops fetalis,
      and those with hydrops fetalis resulting from cardiac defects (group 4). Volume
      data sets of cardiospatiotemporal image correlations were acquired for each group
      for subsequent offline analysis with cardiospatiotemporal image correlation with
      M-mode display. Group 1 data were used to construct reference ranges of left and
      right ventricular shortening fraction for assessment of fetuses in the remaining
      groups. RESULTS: A total of 606 measurements, 15-35 per week, were performed in
      normal fetuses to construct reference ranges as well as Z-scores of left and
      right ventricular shortening fraction. Both parameters were decreased with
      increasing gestation with weak correlation (r2=0.141, P<.001 and r2=0.055,
      P<.001, respectively). Shortening fraction did not significantly change among 111
      fetuses with hemoglobin Bart's disease with and without hydrops. However, left
      and right ventricular shortening fraction were significantly decreased (mean Z
      scores 5 standard deviations and 8 standard deviations below the mean,
      respectively) in 21 hydropic fetuses as a result of congenital heart defects
      (P<.001). CONCLUSION: Fetuses with hydrops fetalis secondary to cardiac defects
      and anemia have a different pattern of shortening fraction. Hydrops fetalis
      resulting from cardiac defect is primarily caused by cardiac decompensation;
      whereas in fetal anemia, it is probably caused by hypervolemia with cardiac
      decompensation occurring when the cardiac compensatory mechanism is exhausted.
      LEVEL OF EVIDENCE: II.

PMID- 21173647
TI  - Early elevations of the complement activation fragment C3a and adverse pregnancy
      outcomes.
AB  - OBJECTIVE: To estimate whether elevations of complement C3a early in pregnancy
      are predictive of the subsequent development of adverse pregnancy outcomes.
      METHODS: A plasma sample was obtained from each enrolled pregnant woman before 20
      weeks of gestation. The cohort (n=1,002) was evaluated for the development of
      adverse pregnancy outcomes defined as hypertensive diseases of pregnancy
      (gestational hypertension or preeclampsia), preterm birth (before 37 weeks of
      gestation), premature rupture of the membranes, pregnancy loss (during the
      embryonic and fetal period), intrauterine growth restriction, and the composite
      outcome of any adverse outcome. RESULTS: One or more adverse pregnancy outcomes
      occurred in 211 (21%) of the cohort. The mean levels (ng/mL) of C3a in early
      pregnancy were significantly (P=<.001) higher among women with one or more
      adverse outcomes (858+/-435) compared with women with an uncomplicated pregnancy
      (741+/-407). Adjusted for parity and prepregnancy body mass index, women with
      levels of C3a in the upper quartile in early pregnancy were three times more
      likely to have an adverse outcome later in pregnancy compared with women in the
      lowest quartile (95% confidence interval, 1.8-4.8; P<.001). The link between
      early elevated C3a levels and adverse pregnancy outcomes was driven primarily by
      individual significant (P<.05) associations of C3a with hypertensive diseases of
      pregnancy, preterm birth, and premature rupture of the membranes. CONCLUSION:
      Elevated C3a as early as the first trimester of pregnancy is an independent
      predictive factor for adverse pregnancy outcomes, suggesting that complement
      related inflammatory events in pregnancy contribute to the subsequent development
      of poor outcomes at later stages of pregnancy. LEVEL OF EVIDENCE: II.

PMID- 21173649
TI  - Lifestyle challenges in endometrial cancer survivorship.
AB  - OBJECTIVE: To examine lifestyle behaviors that may contribute to endometrial
      cancer survivor morbidity and to identify associations with quality of life.
      METHODS: Patients with early-stage (I or II) endometrial cancer with a body mass
      index of at least 25 kg/m2 completed questionnaires on smoking, physical
      activity, fruit and vegetable intake, and the Functional Assessment of Cancer
      Therapy (FACT) and Short-Form medical outcomes (SF-36) quality-of-life surveys.
      Behaviors were compared with American Cancer Society 2006 guidelines for cancer
      survivors (150 min/wk of moderate-to-vigorous physical activity; five servings
      fruit and vegetables per day; no smoking). Effect size (d) was calculated for the
      difference in means between meeting and not meeting guidelines (d=0.5 moderate
      effect). RESULTS: A total of 120 participants were enrolled. Of those, 43% had
      hypertension, 35% osteoarthritis, 33% metabolic syndrome, 21% type 2 diabetes
      mellitus, and 93% abdominal obesity. Only 12% of participants were meeting
      physical activity guidelines. Fifteen percent reported five or more servings of
      fruit and vegetables per day; mean intake was 2.6 servings per day. Seventy-four
      percent of participants were nonsmokers. Only 1% of participants met all three
      American Cancer Society guidelines; 22% met none of the recommendations. The
      emotional well-being (mean 17.4 [+/-4.1] compared with 20.1 [+/-4.1]; d=0.66) and
      fatigue scores (mean 34.6 [+/-9.5] compared with 40.5 [+/-9.6]; d=0.62) indicate
      that those who do not meet the guidelines had lower emotional well-being and
      increased fatigue. CONCLUSION: Endometrial cancer survivors have unhealthy
      lifestyles that put them at risk for morbidity. This survivor group should be
      offered multi-behavioral lifestyle interventions after diagnosis. CLINICAL TRIAL
      REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT 00420979 and
      NCT00732173. LEVEL OF EVIDENCE: II.

PMID- 21173650
TI  - Clearance of human papillomavirus in women treated for cervical dysplasia.
AB  - OBJECTIVE: To estimate human papillomavirus (HPV) clearance of women with
      cervical abnormalities after treatment. METHODS: Women attending dysplasia
      clinics between 2001 and 2007 with a new diagnosis of high-grade dysplasia or
      persistent low-grade dysplasia requiring treatment by excision or laser ablation
      were invited to participate. Cervical cytology, histology of biopsies collected
      at colposcopy, and HPV DNA detection and genotyping of 37 HPV genotypes on
      specimens collected at treatment and subsequent routine visits were examined. A
      log-rank test was used to compare the survival distribution between groups.
      RESULTS: Of the 1,649 women eligible at treatment (baseline), 1,207 (73%) were
      included in the analysis; 96% (n=1,159) had three or more posttreatment visits.
      At baseline and the subsequent three follow-up visits, the prevalence of women
      with HPV DNA detected was 84%, 53% (on average, 6.3 months after baseline), 44%
      (on average, 15.7 months after baseline), and 45% (on average, 24.3 months after
      baseline). The median time to HPV clearance was approximately 6 months for either
      HPV 16 (n=387) or HPV 18 (n=96), irrespective of concurrent detection of other
      types. On average, HPV 16 or HPV 18 types cleared faster than other types
      (P<.001). This association remained significant after adjustment for age,
      preoperative histology, number of preoperative histology results, and treatment
      type. CONCLUSION: Clearance times of HPV 16 and HPV 18 infections were similar to
      each another but shorter than other HPV types. LEVEL OF EVIDENCE: III.

PMID- 21173651
TI  - Bipolar radiofrequency compared with thermal balloon endometrial ablation in the
      office: a randomized controlled trial.
AB  - OBJECTIVE: To estimate the feasibility of local anesthetic endometrial ablation
      in the office using bipolar radiofrequency endometrial ablation or thermal
      balloon ablation technologies and to estimate which procedure alleviates heavy
      menstrual bleeding and improves quality of life more effectively. METHODS: A
      single-center, single-blind, randomized controlled trial was conducted based in
      an office hysteroscopy clinic in a university teaching hospital. Eighty-one women
      with heavy menstrual bleeding without significant intracavity pathology were
      randomly allocated to bipolar radiofrequency endometrial ablation or thermal
      balloon ablation in an office setting, avoiding use of general anesthesia or
      conscious sedation. The primary outcome assessed was the rate of amenorrhea at 6
      months after treatment. Secondary outcomes included procedure-related data
      (feasibility, pain, acceptability, complications) and health-related quality of
      life. RESULTS: Amenorrhea rates were higher at 6 months after surgery with
      bipolar procedures, but not statistically significant (39% compared with 21%,
      risk ratio 1.9, 95% confidence interval 0.9-4.3, P=.1). All bipolar procedures
      were successfully completed, whereas the treatment cycle was not completed in 2
      of 39 (5%) balloon procedures (P>.1) because of patient discomfort. The office
      bipolar procedure was significantly shorter, by 6.2 minutes on average (P<.001),
      and associated with more complete coverage of the endometrial surface (88%
      compared with 58%, P=.002). Health-related quality of life was significantly
      improved after both treatments. CONCLUSION: Office endometrial ablation using the
      bipolar radiofrequency or thermal balloon procedures is feasible and effective.
      The bipolar procedure was significantly quicker and achieved a greater degree of
      endometrial destruction than the thermal balloon, although there was no
      significant difference in amenorrhea rates at 6 months. CLINICAL TRIAL
      REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01124357. LEVEL OF
      EVIDENCE: I.

PMID- 21173652
TI  - Rate of wound complications with enoxaparin use among women at high risk for
      postpartum thrombosis.
AB  - OBJECTIVE: To estimate the rate of wound complications associated with protocol
      driven postcesarean enoxaparin thromboprophylaxis. METHODS: After implementing an
      Institutional Clinical Practice Guideline for postoperative cesarean delivery
      thromboprophylaxis among at-risk gravid women (older than 35 years of age, body
      mass index greater than 30 kg/m2, or both), data on all cesarean deliveries over
      the first 23 months of guideline implementation were extracted and analyzed.
      Primary (wound hematoma, separation, or dehiscence) and secondary (venous
      thromboembolism) outcomes were compared in stratified and multivariable models
      controlling for potential confounders. RESULTS: Over 23 months, 2,509 cesarean
      deliveries were performed. A total of 1,677 (68%) gravid women met criteria for
      thromboprophylaxis; 653 received enoxaparin per protocol ("cases"), and, at the
      discretion of the ordering physician, 1,024 did not (at-risk, protocol
      noncompliant "controls"). Cases differed significantly by virtue of maternal age,
      body mass index, and diabetic status. Univariable analysis subsequently revealed
      a higher rate of wound separation (6.8% compared with 3.6%, P=.003),
      rehospitalization (2.1% compared with 0.8%, P=.017) and composite score (8.9%
      compared with 4.8%, P=.002) among protocol-compliant cases, but no increased risk
      of wound hematoma (P>.06). In multivariable analysis, adjusted odds ratios
      continued to reveal an association between enoxaparin use and wound separation
      (OR 1.66, P=.04) as well as higher composite score (OR 1.69, P=.01). However,
      among the protocol-noncompliant controls, a nonsignificant increase in the rate
      of venous thromboembolism occurred. CONCLUSION: In our series, prophylactic
      enoxaparin use among at-risk gravid women undergoing cesarean delivery was
      accompanied by an increased risk of wound separation. LEVEL OF EVIDENCE: II.

PMID- 21173654
TI  - Optimal interval for ultrasound surveillance in monochorionic twin gestations.
AB  - OBJECTIVE: To examine the association between interval from previous
      ultrasonogram to diagnosis of twin-twin transfusion syndrome and stage at
      diagnosis. METHODS: We reviewed all monochorionic twins undergoing evaluation for
      twin-twin transfusion syndrome in our ultrasound department from 2001 to 2008.
      Cases of twin-twin transfusion syndrome were categorized as early (Quintero
      stages I and II) or late (Quintero stages III-V). The gestational age at
      diagnosis and the interval from the last ultrasonogram were recorded. The
      interval was categorized as 14 days or less or greater than 14 days. Pregnancies
      diagnosed with twin-twin transfusion syndrome at the initial ultrasonogram were
      categorized as greater than 14 days. The univariable association between interval
      from last scan and twin-twin transfusion syndrome stage was determined by chi2.
      P<.05 was considered significant. RESULTS: One-hundred eight monochorionic twin
      pregnancies were identified, and 42 met criteria for twin-twin transfusion
      syndrome: 24 with early stage and 18 with late stage. The median gestational age
      at diagnosis was 19 6/7 (15 3/7-36 3/7) weeks. Twin-twin transfusion syndrome was
      more likely to be diagnosed at a later stage with an ultrasound interval greater
      than 14 days (P=.004). Two cases (11.8%) of late twin-twin transfusion syndrome
      were diagnosed in pregnancies with an ultrasound interval of 14 days or less.
      CONCLUSION: An interval of greater than 14 days from previous ultrasonogram was
      strongly associated with detection of higher-stage twin-twin transfusion
      syndrome. These data suggest that a maximum surveillance interval of 14 days for
      monochorionic twins may lead to earlier stage at diagnosis, earlier intervention,
      and better outcomes. LEVEL OF EVIDENCE: III.

PMID- 21173655
TI  - Effect of alcohol consumption on in vitro fertilization.
AB  - OBJECTIVE: To estimate whether alcohol use at the initiation of an in vitro
      fertilization (IVF) cycle is associated with IVF outcomes. METHODS: In this
      prospective cohort study, men and women completed a self-administered
      questionnaire before their first IVF cycle. Participants reported alcohol type,
      amount, and frequency consumed. Discrete survival analysis was applied to
      calculate the odds ratio (OR) and 95% confidence interval (CI) for live birth-the
      primary outcome. Secondary outcomes were cycle characteristics and points of
      failure in the IVF process (cycle cancellation, failed fertilization,
      implantation failure, and spontaneous abortion). We conducted multicycle analyses
      with final models adjusted for potential confounders that included cycle number,
      cigarette use, body mass index, and age. RESULTS: A total of 2,545 couples
      contributed 4,729 cycles. Forty-one percent of women and 58% of men drank one to
      six drinks per week. Women drinking at least four drinks per week had 16% less
      odds of a live birth rate compared with those who drank fewer than four drinks
      per week (OR 0.84, CI 0.71-0.99). For couples in which both partners drank at
      least four drinks per week, the odds of live birth were 21% lower compared with
      couples in which both drank fewer than four drinks per week (OR 0.79; CI 0.66
      0.96). CONCLUSION: Consumption of as few as four alcoholic drinks per week is
      associated with a decrease in IVF live birth rate. LEVEL OF EVIDENCE: II.

PMID- 21173656
TI  - Where once there was color.

PMID- 21173653
TI  - Cytokine gene polymorphisms and length of gestation.
AB  - OBJECTIVE: To estimate whether there is an association between length of
      gestation and gene polymorphisms that effect transcription of tumor necrosis
      factor-alpha (TNF-alpha), interleukin-6 (IL-6), or interleukin-1beta (IL-1beta).
      METHODS: Blood for DNA analysis was collected from 834 women at high risk
      enrolled in a randomized, clinical trial of omega-3 fatty acid supplementation
      for the prevention of recurrent preterm birth. Genotyping was performed for three
      single nucleotide polymorphisms (SNPs), TNF-alpha -308, IL-6 -174, and IL-1beta
      +3954. Women with the homozygous minor genotype were compared with women with
      either the heterozygous or the homozygous major genotype. Kaplan-Meier curves of
      gestational age at delivery and odds ratios for extreme preterm delivery were
      adjusted for African-American race and treatment group. RESULTS: Women who were
      homozygous for the minor allele at the -308 position in the promoter region of
      the TNF-alpha gene had significantly shorter length of gestation than women who
      were either heterozygous or homozygous for the major allele (adjusted hazard
      ratio 1.74, 95% confidence interval [CI] 1.04-2.90, P=.03). Among women with this
      genotype, 20% (3/15) experienced extreme spontaneous preterm delivery (less than
      28 weeks of gestation; adjusted odds ratio 7.51, 95% CI 1.84-30.72, P=.005).
      There was no difference in length of gestation or risk of extreme spontaneous
      preterm delivery by genotype for the IL-6 -174 or the IL-1beta +3954 SNP.
      CONCLUSION: Polymorphism at the -308 position in the TNF-alpha promoter region is
      associated with shorter gestation and an increased risk of spontaneous extreme
      preterm delivery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
      www.clinicaltrials.gov, NCT00135902. LEVEL OF EVIDENCE: II.

PMID- 21173657
TI  - Increased risk for abnormal depression scores in women with polycystic ovary
      syndrome: a systematic review and meta-analysis.
AB  - OBJECTIVE: Polycystic ovary syndrome (PCOS) and depression both have a high
      prevalence in reproductive-aged women. This study aimed to determine the
      prevalence of abnormal depression scores in women who meet currently recognized
      definitions of PCOS compared with women in a well-defined control group. DATA
      SOURCES: The search was performed in MEDLINE, EMBASE Classic plus EMBASE,
      PsycINFO, Current Contents-Clinical Medicine and Current Contents-Life Sciences
      and Web of Science. Cochrane software Review Manager 5.0.24 was used to construct
      forest plots comparing risk of abnormal depression scores in those in the PCOS
      and control groups. METHODS OF STUDY SELECTION: Studies with well-defined
      criteria of women with PCOS and control groups of women without PCOS, with
      demographic information including age and body mass index (BMI), were included.
      Of 752 screened articles, 17 met the selection criteria for systematic review and
      10 studies were included in the meta-analysis. TABULATION, INTEGRATION, AND
      RESULTS: Data were abstracted independently by three reviewers. All studies were
      cross-sectional and most used the Rotterdam criteria for the diagnosis of PCOS
      (n=10). The odds ratio (OR) for abnormal depression scores was 4.03 (95%
      confidence interval [CI] 2.96-5.5, P<.01) in women with PCOS (n=522) compared
      with those in the control groups (n=475). A subanalysis showed that the odds for
      abnormal depression scores was independent of BMI (OR 4.09, 95% CI 2.62-6.41).
      Several validated tools were used to screen for depression; the common tool used
      was the Beck Depression Inventory. CONCLUSION: The results of our study suggest
      the need to screen all women with PCOS for depression using validated screening
      tools. Women with PCOS are at an increased risk for abnormal depression scores
      independent of BMI.

PMID- 21173658
TI  - The effect of periodontal therapy on preterm low birth weight: a meta-analysis.
AB  - OBJECTIVE: To systematically review the randomized controlled trials that
      evaluated the effect of periodontal therapy on preterm birth and low birth weight
      (LBW). DATA SOURCES: A systematic search was conducted of the PubMed, Bireme,
      LILACS, and Cochrane databases. METHODS OF STUDY SELECTION: Only randomized
      controlled trials on the effect of periodontal therapy on preterm birth and LBW
      were included. The Consolidated Standards of Reporting Trials statement was used
      in quality assessment and meta-analysis was carried out using random-effects
      methods. TABULATION, INTEGRATION, AND RESULTS: The search resulted in 14 clinical
      studies. Ten articles met the inclusion criteria for preterm birth and four for
      LBW. Five meta-analyses on preterm birth were performed according to different
      criteria: 1) use of probing depth and attachment loss for periodontitis
      definition, relative risk (RR) 0.58 (95% confidence interval [CI] 0.29-1.12)
      (four studies); 2) controlling for multiparity, RR 0.92 (95% CI 0.72-1.17) (eight
      studies); 3) controlling for previous preterm birth, RR 0.88 (95% CI 0.67-1.16)
      (seven studies); 4) controlling for genitourinary infections, RR 0.75 (95% CI
      0.57-1.05) (six studies); and 5) all the previous criteria, RR 0.63 (95% CI 0.32
      1.22) (three studies). Three meta-analysis on LBW were conducted according to
      controlling for multiparity, RR 1.03 (95% CI 0.76-1.40) (four studies);
      controlling for previous preterm birth, RR 0.93 (95% CI 0.65-1.30) (three
      studies); and use of probing depth and attachment loss for periodontitis
      definition, controlling for multiparity, previous preterm birth, and
      genitourinary infections, RR 0.52 (95% CI 0.10-2.60) (two studies). In all meta
      analyses, the effect of periodontal treatment on preterm birth and LBW was not
      statistically significant. CONCLUSION: Results of this meta-analysis do not
      support the hypothesis that periodontal therapy reduces preterm birth and LBW
      indices.

PMID- 21173660
TI  - Pharmaceutical policies: effects of restrictions on reimbursement.

PMID- 21173659
TI  - Consent for autopsy research for unexpected death in early life.
AB  - Research in sudden death in fetuses (stillbirth) and infants (sudden infant death
      syndrome [SIDS]) is urgently needed, particularly in high-risk populations
      involving socioeconomic disadvantaged families. Essential to such research is the
      analysis of fetal and infant tissues at autopsy. Obtaining consent for donating
      autopsy tissues for research is especially problematic in socioeconomically
      disadvantaged populations in which mistrust of the medical establishment often
      exists. In this article, we present communication strategies for obtaining
      consent for research in autopsy tissues of stillbirth and SIDS cases in
      socioeconomically disadvantaged populations. Recommendations are provided about
      preparation for and the timing, setting, and content of the consent interview.
      The same lines of open and transparent communication delineated in this article
      are applicable to obtaining consent for the autopsy and autopsy research.
      Although the grief responses to the untimely death of the fetus or infant are
      universal and the recommendations of this essay are widely applicable to the
      general population, the expression of this grief and feelings toward autopsy
      based research in socioeconomically disadvantaged populations may raise special
      issues that health care workers should be aware of when obtaining consent for
      research on autopsy-derived tissues.

PMID- 21173661
TI  - Pregnancy outcomes in women with thyroid peroxidase antibodies.

PMID- 21173663
TI  - The residency certificate: the rite of passage.

PMID- 21173666
TI  - Tranexamic acid treatment for heavy menstrual bleeding: a randomized controlled
      trial.

PMID- 21173668
TI  - Congenital fetal heart block: a potential therapeutic role for intravenous
      immunoglobulin.

PMID- 21173670
TI  - Retraction. ACOG Committee Opinion No. 281: Rubella vaccination.

PMID- 21173671
TI  - ACOG Practice Bulletin No. 118: antiphospholipid syndrome.

PMID- 21173672
TI  - AGOG Committee Opinion No. 473: substance abuse reporting and pregnancy: the role
      of the obstetrician-gynecologist.
AB  - Drug enforcement policies that deter women from seeking prenatal care are
      contrary to the welfare of the mother and fetus. Incarceration and the threat of
      incarceration have proved to be ineffective in reducing the incidence of alcohol
      or drug abuse. Obstetrician-gynecologists should be aware of the reporting
      requirements related to alcohol and drug abuse within their states. They are
      encouraged to work with state legislators to retract legislation that punishes
      women for substance abuse during pregnancy.

PMID- 21173674
TI  - Impact of human immunodeficiency virus infection on the etiology and outcome of
      severe pneumonia in Malawian children.
AB  - BACKGROUND: HIV infection is a major risk factor for death in childhood pneumonia
      in HIV-endemic regions. Improved case management and preventive strategies
      require better understanding of the impact of HIV on causes, clinical
      presentation, and outcome. METHODS: A prospective, clinical descriptive study of
      Malawian infants and children with severe pneumonia included blood culture and
      nasopharyngeal aspiration for diagnosis of pneumocystis pneumonia (PcP). A select
      group with consolidation on chest radiograph, and without severe hypoxia or
      hyperinflation, also had lung aspirate taken for culture and identification of
      bacterial deoxyribonucleic acid by real-time polymerase chain reaction (PCR).
      RESULTS: There were 327 study patients with a median age of 11 months (range, 2
      months-14 years). HIV prevalence was 51%. There were 58 cases of confirmed
      bacterial pneumonia, of which the most common bacterial isolates were
      Streptococcus pneumoniae and Salmonella typhimurium. Of the 54 lung aspirates,
      only 2 were positive on culture but 27 were positive for bacterial
      deoxyribonucleic acid by PCR. PcP was confirmed in 16 patients, and was
      associated with young age, severe hypoxia, HIV infection, and a very poor
      outcome. The overall case-fatality rate was 10% despite presumptive therapy for
      PcP and routine broad-spectrum antibiotic treatment appropriate for local
      antimicrobial susceptibility data. Most of the deaths occurred in infants of 2 to
      6 months of age and PcP was associated with 57% of these deaths. CONCLUSIONS: PcP
      is a major barrier in reducing the case-fatality rate of severe pneumonia in
      infants of HIV-endemic communities. The use of PCR on lung aspirate specimens
      greatly increased the diagnostic yield.

PMID- 21173675
TI  - Morbidity among human immunodeficiency virus-exposed but uninfected, human
      immunodeficiency virus-infected, and human immunodeficiency virus-unexposed
      infants in Zimbabwe before availability of highly active antiretroviral therapy.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) remains a major cause of pediatric
      morbidity in Africa. In addition, HIV-exposed, but uninfected (HEU) infants can
      comprise a substantial proportion of all infants born in high prevalence
      countries and may also be a vulnerable group with special health problems.
      METHODS: A total of 14,110 infants were recruited within 96 hours of birth
      between November 1996 and January 2000. Rates and causes of sick clinic visits
      and hospitalizations during infancy were investigated according to infant HIV
      infection group: infected-intrauterine, infected-intrapartum, postnatally
      infected, HEU, and not-exposed (born to HIV-negative mother). RESULTS: A total of
      382 infected-intrauterine, 499 infected-intrapartum, 188 postnatally-infected,
      2849 HEU, and 9207 not-exposed infants were included in the analysis. Compared
      with not-exposed infants, HIV-infected infants made 2.8 times more all-cause sick
      clinic visits and required 13.3 times more hospitalizations; they had 7.2 times
      more clinic visits and 23.5 times more hospitalizations for lower respiratory
      tract infection after the neonatal period and were 159.9 times more likely to be
      hospitalized for malnutrition during the second half of infancy. Compared with
      not-exposed infants, sick clinic visits were 1.2 times more common among HEU
      infants, were inversely associated with maternal CD4 cell count, and were
      significantly higher for all HEU infants except those whose mothers had a CD4
      count >= 800 cells/MUL, which was the mean value of HIV-negative women enrolled
      in the trial. CONCLUSIONS: Morbidity is extremely high among HIV-infected
      infants. Compared with not-exposed infants, morbidity is higher among HEU infants
      and increases with severity of maternal disease, but is significantly higher for
      all mothers with CD4 cell count <800 cells/MUL.

PMID- 21173676
TI  - Viral gastroenteritis in children.

PMID- 21173677
TI  - West Nile Virus infections in children: a disease pediatricians should think
      about.

PMID- 21173678
TI  - Pandemic A (H1N1) influenza in hospitalized children in Warsaw, Poland.

PMID- 21173679
TI  - Is it time to study TLR3 or UNC-93B pathway deficiencies in reactivated herpes
      simplex encephalitis?

PMID- 21173680
TI  - Amoebic abscess of the spleen and fatal colonic perforation.

PMID- 21173681
TI  - Acute encephalopathy in a child with secondary carnitine deficiency due to
      pivalate-conjugated antibiotics.

PMID- 21173682
TI  - The frequency of lymphedema in an adult spina bifida population.
AB  - OBJECTIVE: In the United States, there are more than 100,000 people with spina
      bifida. There have been very few studies to date documenting the occurrence of
      lymphedema in the spina bifida population, despite a case series in 2001 that
      suggested that the occurrence may be higher than in the general population.
      Currently, approximately 1 million people have lymphedema in the United States.
      The purpose of this study was to document the occurrence of lymphedema and
      associated medical factors in a regional adult spina bifida population. DESIGN: A
      total of 240 electronic medical records from the Adult Spina Bifida Clinic from
      January 2005 to August 2008 were retrospectively reviewed. Subjects were divided
      into two groups based on the presence or absence of lymphedema. chi2 analyses
      were used to compare lymphedema groups with respect to history of medical
      comorbidities and ethnicity. Fisher exact tests were used to compare groups with
      respect to mobility status and the presence of power wheelchair seat functions.
      Mann-Whitney U tests were used to compare groups with respect to age, anatomic
      lesion level, employment level, and income. RESULTS: Twenty-two (9.2%) patients
      had lymphedema. Mean +/- SD population age was 35.1 +/- 11.1 yrs. Lymphedema was
      associated with a history of trauma (P = 0.044), cellulitis (P < 0.001), cancer
      (P = 0.038), obesity (P < 0.001), wounds (P < 0.001), hypertension (P = 0.036),
      higher lesion level spina bifida (P = 0.049), and mobility status (P = 0.007).
      Hypertension and obesity were present in 38.3% and 37.5% of the total study
      population, respectively. CONCLUSIONS: This is the first study to document the
      occurrence of lymphedema in a spina bifida patient population, which was almost
      100 times higher than that in the general patient population. We also documented
      a high occurrence of hypertension and obesity in the total study population.
      These findings may help guide further prospective studies to more clearly
      delineate the risk factors for the development of lymphedema and to determine the
      appropriate therapies. Better screening, prevention and treatment algorithms are
      needed for hypertension and obesity in the spina bifida population.

PMID- 21173683
TI  - Do unblinded assessors bias muscle strength outcomes in randomized controlled
      trials of progressive resistance strength training in older adults?
AB  - OBJECTIVE: Knowledge of treatment assignment and failing to analyze results by
      randomized treatment groups--an intention-to-treat analysis--may cause bias in
      the treatment effect estimate in randomized controlled trials. This study was
      undertaken to determine the difference in lower limb muscle strength measured by
      blinded vs. by unblinded outcome assessors in 73 progressive resistance strength
      training trials conducted in older adults. DESIGN: Retrospective analysis of
      randomized controlled trials published before 2007. RESULTS: Meta-regression
      analyses showed that trials that used blinded assessors (n = 18) tend to report
      smaller effect sizes than do those that used unblinded assessors (n = 55), with a
      difference of -0.80 (95% confidence interval, -1.35 to -0.25). This result still
      holds even after adjusting for the use of an intention-to-treat analysis, with an
      adjusted difference of -0.65 (95% confidence interval, -1.26 to -0.04). The
      reported effects were exaggerated in trials that used unblinded assessors.
      CONCLUSIONS: This study suggests that assessor blinding is important and is a
      safeguard to the internal validity of exercise trials in older adults.

PMID- 21173684
TI  - Effect of physiologic ischemic training on protection of myocardial infarction in
      rabbits.
AB  - OBJECTIVE: The aim of this study was to investigate the protective effect of
      physiologic ischemic training of normal skeletal muscle against myocardial
      infarction. DESIGN: Thirty-five rabbits were implanted with water balloon
      constrictors in the left ventricular branch to cause myocardial ischemia and an
      electrode near the left sciatic nerve for electric muscle stimulation for
      physiologic ischemic training. Three groups were randomly selected: the pure
      ischemia (PI) group received myocardial ischemia for 2 mins, two times a day,
      five times a week; the exercise training (ET) group received myocardial ischemia
      as did the PI group, plus 4 mins of physiologic ischemic training, two times a
      day, five times a week; and the sham-operated (SO) group was the sedentary
      controls. After 4 wks of training, the left ventricular branch was occluded to
      cause infarction. Infarct size was measured by magnetic resonance imaging; left
      ventricular ejection fraction, by echocardiogram; capillary density, by
      immunohistochemistry; and collateral circulation blood flow, by a microsphere
      technique. RESULTS: The ET group's infarct size was significantly smaller than
      that of the PI group (P < 0.01) and the SO group (P < 0.01). Change in left
      ventricular ejection fraction in the ET group was significantly lower than in the
      SO group (P < 0.01), and capillary density in the ET group was significantly
      higher than in the PI group (P< 0.01) and the SO group (P < 0.01). Collateral
      circulation blood flow in the ET group was significantly higher than in the PI
      group (P < 0.01) and the SO group (P< 0.01). Capillary density was significantly
      correlated with endpoint collateral circulation blood flow (r = 0.91, P = 0.000),
      infarct size (r = -0.91, P = 0.000), and change in left ventricular ejection
      fraction (r = -0.94, P = 0.000). CONCLUSIONS: Physiologic ischemic training of
      skeletal muscle may induce collateral circulation development in the myocardium,
      thus decreasing infarct size when infarction occurs.

PMID- 21173685
TI  - Ultrasound assessment of bilateral longus colli muscles in subjects with chronic
      bilateral neck pain.
AB  - OBJECTIVE: The aim of this study was to investigate bilateral differences in the
      cross-sectional area (CSA) and shape ratio of the longus colli muscle between
      subjects with mechanical neck pain and healthy controls. DESIGN: A case-control
      cohort study was conducted. Bilateral ultrasound images of the longus colli
      muscle at the thyroid (C5-C6) level were conducted in 20 patients with mechanical
      bilateral chronic neck pain and 20 controls by an assessor blinded to the
      subjects' condition. CSA, anterior-posterior dimension (APD), lateral dimension
      (LD), and shape ratio (LD/APD) were measured. RESULTS: The intraclass correlation
      coefficients (3,1) were above 0.86 for within-day and above 0.81 for between-day
      intraexaminer reliability. Patients with mechanical neck pain showed bilateral
      smaller CSA (P < 0.001) and APD (P = 0.004) as compared with controls. Muscle
      shape and LD were not different between groups (P = 0.092 and P = 0.963,
      respectively). Women exhibited smaller bilateral CSA as compared with men (P <
      0.01). CSA was negatively associated with self-reported disability, whereas APD
      was negatively associated with intensity of neck pain: the greater the self
      reported disability or the pain intensity, the smaller the bilateral CSA or APD
      of the longus colli muscle. CONCLUSIONS: The longus colli muscle exhibited
      smaller bilateral CSA and APD, but not LD and shape ratio, in subjects with
      bilateral chronic neck pain as compared with healthy controls. Reduced CSA was
      negatively associated with self-reported disability and APD was negatively
      associated with the intensity of pain.

PMID- 21173686
TI  - Detectable threshold of knee effusion by ultrasonography in osteoarthritis
      patients.
AB  - OBJECTIVE: The aim of this study was to identify the detectable threshold of knee
      effusion by ultrasonography while infusing saline. DESIGN: Forty knee
      osteoarthritis patients were allocated randomly to either the midline or the
      lateral group. Intra-articular injection of 20 ml normal saline was performed
      under ultrasonographic guidance with the transducer fixated at the midline
      longitudinal or lateral longitudinal scan in the midline and lateral groups,
      respectively. We obtained ultrasonography images after infusing each milliliter
      and measured the maximum depth of effusion. RESULTS: The smallest amount of
      infusion detected by ultrasonography was 4.37 +/- 2.11 ml in the midline group
      and 4.13 +/- 1.71 ml in the lateral group. An effusion more than 2 mm deep was
      observed after infusing 7.84 +/- 3.85 ml and 7.38 +/- 3.01 ml in the midline and
      lateral groups, respectively. To obtain a 4-mm depth, infusions of 11.58 +/- 5.68
      ml and 13.13 +/- 4.88 ml were needed in the midline and lateral groups,
      respectively. CONCLUSIONS: To detect knee effusion by ultrasonography, infusion
      of 4.26 ml (SD, 1.92 ml) of solution is needed. We think that a depth of 2 mm is
      more appropriate than 4 mm as the definition of knee effusion using
      ultrasonography.

PMID- 21173687
TI  - Change in thigh muscle cross-sectional area through administration of an anabolic
      steroid during routine stroke rehabilitation in hemiplegic patients.
AB  - OBJECTIVE: The aim of this study was to clarify the effect of administration of
      an anabolic steroid (AS) without the addition of specific training in stroke
      patients by measuring the cross-sectional area (CSA) of the thigh. DESIGN: Twenty
      six hemiplegic stroke patients during subacute rehabilitation were randomly
      assigned to a metenolone enanthate (ME) administration group or a control group
      (CT group). In the ME group, ME (100 mg) was injected intramuscularly weekly for
      6 wks in the ME group. The CSA of the bilateral thigh muscles was measured using
      computed tomography. Motor subscore of the Functional Independence Measure (FIM
      M) was assessed before the experimental period. RESULTS: At the end of 6 wks, the
      CSA increase in the ME group (13.4%, affected side; 14.5%, unaffected side) was
      significantly larger than that in the CT group (3.3%, affected side; 5.2%,
      unaffected side). Correlation coefficients between the initial FIM-M score and
      the CSA increase at 6 wks were -0.754 for the affected side and -0.567 for the
      unaffected side in the ME group and 0.199 for the affected side and 0.431 for the
      unaffected side in the CT group. CONCLUSIONS: ME administration is effective for
      improving muscle CSA and, thus, muscle strengthening in stroke rehabilitation.
      The CSA increase in the ME group was most prominent in patients with a low
      initial FIM-M score.

PMID- 21173688
TI  - Respiratory physical medicine: Physiatry's neglected discipline.

PMID- 21173689
TI  - Assessing the quality of surgical trials: further insight.

PMID- 21173690
TI  - Polycystic liver disease: a critical appraisal of hepatic resection, cyst
      fenestration, and liver transplantation.

PMID- 21173691
TI  - The impact of surgery on survival of patients with cutaneous melanoma: revisiting
      the role of primary tumor excision margins.
AB  - OBJECTIVE: To quantify the impact of excision margins on disease-specific
      survival of patients with primary cutaneous melanoma. BACKGROUND: Current
      guidelines recommend narrow margins for the treatment of primary melanoma,
      although available evidence on this subject is not unequivocal and not always
      appropriately analyzed. METHODS: A systematic review of randomized controlled
      trials (RCT) addressing the issue of wide versus narrow excision margins was
      performed. Meta-analysis methods for time-to-event data were used to extract
      hazard ratios(HR) and their 95% confidence intervals (CI) from eligible studies,
      and ultimately to estimate the summary effect of excision margins on patients'
      survival. RESULTS: The 5 eligible RCT enrolled a total of 3295 patients who were
      allocated to wide (3-5 cm) or narrow (1-2 cm) excision of their primary tumor.
      The data of locoregional disease-free (LDFS), disease-free (DFS),disease-specific
      (DSS), and overall (OS) survival were available for 3, 5, 3, and 5 RCT,
      respectively. The meta-analysis suggested that narrow margins might be associated
      with an increased risk of both locoregional disease recurrence (HR: 1.30, CI:
      1.07-1.57; P = 0.01) and death by disease (HR: 1.28, CI:1.07-1.53, P = 0.01). As
      regards DFS, the borderline disadvantage (HR:1.13, CI: 0.995-1.28; P = 0.06)
      becomes significant when considering RCT that enrolled patients with thicker
      melanoma (HR: 1.19, CI: 1.02-1.39, P =0.03). When death by any cause (OS) was
      analyzed, no risk difference was found. CONCLUSIONS: The lack of DSS data from
      all the available RCT does not allow to draw definitive conclusions. However,
      current evidence appears sufficient to question the common belief that narrow
      excision margins are as safe as wide margins in the management of primary
      melanoma, that calls for further investigation in this field.

PMID- 21173692
TI  - Reducing ethnic disparities in the quality of trauma care: an important research
      gap.
AB  - OBJECTIVE: To identify interventions for reducing ethnic disparities in the
      quality of trauma care. BACKGROUND: Variation in the quality of health care is
      recognized as an important contributor to ethnic disparities in many domains of
      health. Although recent articles document ethnic variations in the quality of
      trauma care in several countries, strategies that address these disparities have
      received little attention. METHODS: Systematic review of intervention studies
      designed to reduce ethnic disparities in trauma care. RESULTS: Our systematic
      literature review revealed no evaluations of interventions designed to reduce
      ethnic disparities in trauma care. A scan of the equivalent literature in other
      health care settings revealed 3 types of strategies that could serve as promising
      interventions that warrant further investigation in the trauma care setting: (1)
      improving cultural competency of service providers, (2) addressing the effects of
      health literacy on the quality of trauma care, and (3) quality improvement
      strategies that recognize equity as a key dimension of quality. The trauma
      coordinator role may help address some aspects relating to these themes although
      reducing disparities is likely to require broader system-wide policies.
      CONCLUSIONS: The implementation and robust evaluation of strategies designed to
      reduce ethnic disparities in trauma care are long overdue.

PMID- 21173693
TI  - Can the impact of change of surgical teams in cardiovascular surgery be measured
      by operative mortality or morbidity? A propensity adjusted cohort comparison.
AB  - OBJECTIVE: Our objective was to examine the impact of team changeover and
      unfamiliar teams in cardiovascular surgery on traditional clinical outcome
      measures. BACKGROUND: The importance of teamwork in the operating room is
      increasingly being appreciated, but the impact on more traditional outcome
      measures is unclear. METHODS: Elective or urgent cardiovascular procedures were
      divided into categories: team D (patients who had an operation with a day team);
      team E (patients who had an operation with an evening team); team C (patients who
      had an operation which included changeover between a day and evening team).
      Comparison groups were adjusted using propensity scores. RESULTS: We identified
      6698 patients who met inclusion criteria (team D, n =3781; team E, n = 518; team
      C, n = 2399). After propensity score adjustment,there was an increased skin-skin
      time of 28 minutes in team C when compared with team D (P < 0.001) and of 21
      minutes when compared with team E (P <0.001). There were also more episodes of
      septicemia among team C patients(OR 1.85, P = 0.013) when compared with team D.
      Patients operated by a day team had a statistically significantly lower number of
      ventilated hours and shorter hospital length of stay when compared with team E
      and team C (P < 0.001 and P < 0.001, respectively). There was no difference
      between teams in operative death, reoperation for bleeding, blood transfusion,
      renal failure/dialysis, neurologic events, or deep/superficial wound infections.
      CONCLUSIONS: The change in operating room personnel from the day team to the
      evening team added significant length to the total operating department time in
      cardiovascular surgery; however, its impact on most traditional outcome measures
      was difficult to demonstrate. More sensitive outcome measures may be required to
      assess the impact of teamwork interventions.

PMID- 21173694
TI  - Screening for thyroid cancer in patients with familial adenomatous polyposis.
AB  - OBJECTIVE: Clarify the incidence of thyroid cancer in patients with Familial
      adenomatous polyposis (FAP) in a prospective study of thyroid neck US screening.
      BACKGROUND: FAP is a hereditary disease predisposing to cancer in multiple
      organs, including the thyroid. However, routine thyroid screening for FAP
      patients is not generally practiced in the United States. Here, we report the
      initial results of a prospective thyroid cancer screening program in patients
      with FAP. METHODS: At the time of yearly gastrointestinal follow-up, every FAP
      patient in our registry was offered thyroid ultrasound (US) performed by
      experienced endocrine surgeons. Clinical findings related to thyroid disease were
      analyzed for those patients who completed screening from August 2008 to December
      2009. RESULTS: : Of 192 screened FAP patients, 72 (38%) had thyroid nodules and 5
      (2.6%) had thyroid cancer. Three of 5 patients with FAP and thyroid cancer were
      women. Four of 5 patients had the multifocal papillary type with mean size 15 mm.
      Clinical history and neck exam did not detect any of the 5 cancers. CONCLUSION:
      The incidence of thyroid cancer among FAP patients is high. Medical history and
      exam are inadequate to identify patients with thyroid cancer, thus thyroid
      screening with US is warranted.

PMID- 21173695
TI  - Improving outcomes after laparoscopic appendectomy: a population-based, 12-year
      trend analysis of 7446 patients.
AB  - OBJECTIVE: Laparoscopic appendectomy for acute appendicitis has become
      increasingly used over the past decade. The objective of this trend analysis is
      to assess whether clinical outcomes after laparoscopic appendectomy have improved
      over the past 12 years. METHODS: This analysis is based on the prospective
      database of the Swiss Association of Laparoscopic and Thoracoscopic Surgery. All
      patients undergoing emergency laparoscopic appendectomy for acute appendicitis
      from 1995 to 2006 were included. The following outcomes were assessed for each of
      the 12 years: conversion rates, intraoperative complications, surgical
      postoperative complications, general postoperative complications, rate of
      reoperations, and length of hospital stay. Unadjusted and risk-adjusted
      multivariable analyses were performed. Statistical significance was set at a
      level of P < 0.05. All statistical tests were 2-sided. RESULTS: Data from 7446
      patients undergoing laparoscopic appendectomy for acute appendicitis were
      prospectively collected. Over the period of observation, the conversion rate
      decreased significantly from 2.2% to 1.2% (P(trend)< 0.001), as did
      intraoperative complications (from 3.1% to 0.7%; P(trend)< 0.001), surgical
      postoperative complications (from 6.1% to 1.9%; P(trend)< 0.001), general
      postoperative complications (from 4.9% to 1.5%; P(trend)< 0.001), and rates of
      reoperations (from 3.4% to 0.7%; P(trend)< 0.001). Average postoperative length
      of hospital stay also significantly decreased from 4.9 to 3.5 days (P(trend)<
      0.001). CONCLUSIONS: Our investigation provides compelling evidence that
      intraoperative complications, surgical and general postoperative complications,
      conversion rates, rates of reoperations, and average length of hospital stay have
      significantly decreased over the past decade in patients undergoing surgery for
      acute appendicitis. The present trend analysis is the first one in the literature
      encompassing more than a decade and reporting clinical outcomes after
      laparoscopic appendectomy for acute appendicitis, which represents an important
      quality control.

PMID- 21173697
TI  - Mucosectomy with handsewn anastomosis reduces the risk of adenoma formation in
      the anorectal segment after restorative proctocolectomy for familial adenomatous
      polyposis.
AB  - OBJECTIVE: The study compared the risk of adenoma or carcinoma formation in the
      anorectal segment after either mucosectomy with manual anastomosis or stapled
      ileoanal anastomosis (IAA) following restorative proctocolectomy (RPC) for
      familial adenomatous polyposis (FAP). BACKGROUND: Few data exist on the risk of
      adenoma formation after either technique in FAP. METHODS: All endoscopy and
      histology reports for patients having RPC for FAP attending for annual
      pouchoscopy from 1978 to 2007 were reviewed. The incidence, timing, and
      histological characteristics of adenoma or carcinoma formation were recorded.
      RESULTS: Of the 206 patients, 140 attended for endoscopic follow-up for a median
      of 10.3 years after RPC. Fifty-two patients developed neoplastic transformation
      in the anorectal segment, with a cumulative risk at 10 years of 22.6% after
      mucosectomy with manual anastomosis and 51.1% after stapled IAA (P < 0.001). The
      median time to first adenoma was longer after mucosectomy with handsewn
      anastomosis than after stapled IAA (10.1 vs 6.5 years, P < 0.001). On
      multivariate analysis, stapled IAA (hazard ratio= 3.45, 95% confidence interval =
      1.01-4.98) and age at RPC older than 40 years (hazard ratio = 2.20, 95%
      confidence interval = 1.01-4.89) were significantly associated with increased
      risk of adenoma formation. Nine patients developed a large (>10 mm) adenoma. One
      patient (handsewn ileoanal anastomosis) developed adenocarcinoma in the anorectal
      mucosa at 13 years and required pouch excision. CONCLUSIONS: Adenoma formation in
      the anorectal mucosa after RPC for FAP is common but carcinoma is rare. The risk
      is lower after mucosectomy with handsewn anastomosis than after stapled IAA.
      Regular endoscopic surveillance after either technique is mandatory.

PMID- 21173696
TI  - A policy-based intervention for the reduction of communication breakdowns in
      inpatient surgical care: results from a Harvard surgical safety collaborative.
AB  - OBJECTIVE: To develop and evaluate an intervention to reduce breakdowns in
      communication during inpatient surgical care. BACKGROUND: Communication
      breakdowns are the second most common cause of avoidable surgical adverse events
      after technical errors. METHODS: In a pre- and postintervention study, a random
      selection of patients on the surgical services of 4 teaching hospitals were
      observed according to 3 measures: (1) resident-attending communication of
      critical patient events (eg, transfer into the intensive care unit, unplanned
      intubation, cardiac arrest); (2) resident-attending notification regarding
      routine weekend patient status; and (3) frequency of weekend patient visits by an
      attending. All departments then developed and adopted a set of policy and
      education initiatives designed to increase prompt and consistent resident
      attending communication (especially in critical events) and to improve regular
      attending visits with surgical patients. Specific reinforcement of the policies
      included a pocket information card for residents, as well as periodic reminders.
      Repeat audits of the surgical services were then conducted. RESULTS: We reviewed
      information for 211 critical events and 1360 patients for the nature of resident
      and attending communication practices. After the intervention, the proportion of
      critical events not conveyed to an attending decreased from 33% (26/80) to 2%
      (1/47), and gaps in the frequency of attending notification of patient status on
      weekends were virtually eliminated (P < 0.0001); the proportion of weekend
      patients not visited by an attending for greater than 24 hours decreased by half
      (from 61% to 33%; P = 0.0002). Contact resulted in attending-led changes in
      patient management in one-third of cases. CONCLUSIONS: An intervention to improve
      surgical communication practices at 4 teaching hospitals led to significant
      reductions in potentially harmful communication breakdowns during inpatient care;
      significant alterations in patient management were noted in one-third of cases in
      which there was an adherence to recommended communication practices.

PMID- 21173698
TI  - Late-onset intrascleral dissemination of Stenotrophomonas maltophilia scleritis
      after pterygium excision.
AB  - PURPOSE: To report a case of pterygium excision-related infectious scleritis with
      late-onset intrascleral dissemination. METHODS: Case report. RESULTS: A 72-year
      old female patient was referred for Stenotrophomonas maltophilia scleritis after
      undergoing pterygium excision 18 years earlier. Surgical debridement and a
      tectonic corneal patch graft, along with conjunctival flap, were performed to
      repair the scleral defect after treatment with fortified topical and systemic
      antibiotics. However, intrascleral dissemination of scleritis occurred 5 months
      after the initial episode. CONCLUSIONS: Intrascleral dissemination of S.
      maltophilia scleritis after pterygium excision might be delayed because of
      limited invasiveness and inherent resistance to several antibiotics. Long-term
      follow-up may be needed to protect against the possibility of late-onset
      intrascleral dissemination.

PMID- 21173699
TI  - The association between mucin balls and corneal infiltrative events during
      extended contact lens wear.
AB  - PURPOSE: To determine the association between mucin ball formation and corneal
      infiltrative events (CIEs) during continuous wear with lotrafilcon A silicone
      hydrogel contact lenses. METHODS: Subjects (n = 205) in the Longitudinal Analysis
      of Silicone Hydrogel Contact Lens Study wore lotrafilcon A contact lenses for 12
      months of continuous wear. The primary outcome was a CIE. Kaplan-Meier methods
      were used to estimate the unadjusted cumulative incidence of remaining CIE free
      stratified by mucin ball presence. Cox proportional hazards regression was used
      to model the hazard of developing a CIE as a function of mucin ball formation and
      other covariates. RESULTS: Over half (54.2%) of the subjects displayed some
      presence of mucin balls during at least 1 visit and about one third (32.8%)
      displayed repeated episodes. Mucin ball scores were correlated between the 2 eyes
      and weakly correlated with corneal curvature (P <= 0.005). Univariate analyses
      revealed that the relative hazard for a CIE was 0.35 [95% confidence interval
      (CI), 0.19-0.68] if a single episode of mucin balls was detected and 0.17 (95%
      CI, 0.06-0.43) if repeated episodes were detected. Upon multivariate analysis,
      repeated presence of mucin balls was associated with an 84% decreased hazard of
      experiencing a CIE (hazard ratio: 0.16; 95% CI, 0.06-0.44). CONCLUSIONS: The
      presence of mucin balls is significantly associated with a decreased incidence of
      CIEs, and the effect is greatest when they are repeatedly present over time. We
      hypothesize that the mucin ball presence represents a more concentrated or
      viscous mucus layer, which prevents upregulation of the immune response against
      bacterial ligands.

PMID- 21173700
TI  - Making a definitive diagnosis: successful clinical application of whole exome
      sequencing in a child with intractable inflammatory bowel disease.
AB  - PURPOSE: We report a male child who presented at 15 months with perianal
      abscesses and proctitis, progressing to transmural pancolitis with colocutaneous
      fistulae, consistent with a Crohn disease-like illness. The age and severity of
      the presentation suggested an underlying immune defect; however, despite
      comprehensive clinical evaluation, we were unable to arrive at a definitive
      diagnosis, thereby restricting clinical management. METHODS: We sought to
      identify the causative mutation(s) through exome sequencing to provide the
      necessary additional information required for clinical management. RESULTS: After
      sequencing, we identified 16,124 variants. Subsequent analysis identified a
      novel, hemizygous missense mutation in the X-linked inhibitor of apoptosis gene,
      substituting a tyrosine for a highly conserved and functionally important
      cysteine. X-linked inhibitor of apoptosis was not previously associated with
      Crohn disease but has a central role in the proinflammatory response and
      bacterial sensing through the NOD signaling pathway. The mutation was confirmed
      by Sanger sequencing in a licensed clinical laboratory. Functional assays
      demonstrated an increased susceptibility to activation-induced cell death and
      defective responsiveness to NOD2 ligands, consistent with loss of normal X-linked
      inhibitor of apoptosis protein function in apoptosis and NOD2 signaling.
      CONCLUSIONS: Based on this medical history, genetic and functional data, the
      child was diagnosed as having an X-linked inhibitor of apoptosis deficiency.
      Based on this finding, an allogeneic hematopoietic progenitor cell transplant was
      performed to prevent the development of life-threatening hemophagocytic
      lymphohistiocytosis, in concordance with the recommended treatment for X-linked
      inhibitor of apoptosis deficiency. At >42 days posttransplant, the child was able
      to eat and drink, and there has been no recurrence of gastrointestinal disease,
      suggesting this mutation also drove the gastrointestinal disease. This report
      describes the identification of a novel cause of inflammatory bowel disease.
      Equally importantly, it demonstrates the power of exome sequencing to render a
      molecular diagnosis in an individual patient in the setting of a novel disease,
      after all standard diagnoses were exhausted, and illustrates how this technology
      can be used in a clinical setting.

PMID- 21173701
TI  - Survey of complementary and alternative medicine use in glaucoma patients.
AB  - PURPOSE: To determine the prevalence, types, and associated factors of
      complementary and alternative medicine (CAM) use in glaucoma patients. PATIENTS
      AND METHODS: Prospective, multicenter, cross-sectional survey. A total of 1516
      consecutive patients attending 2 tertiary glaucoma clinics were surveyed on CAM
      use. Information gathered on standardized data collection sheets included
      demographic variables, ophthalmic history, glaucoma treatment history, and
      details of CAM use. RESULTS: The response rate was 92.5%. A total of 166 patients
      (10.9%) reported current use of CAM therapy specifically for glaucoma whereas 41
      patients (2.7%) reported past use of CAM. Of the patients who reported CAM use,
      62.5% had not disclosed the use of CAM to their ophthalmologist and 40.5%
      believed that the treatments were helping their glaucoma. The most commonly used
      types of CAM were herbal medications (34.5%), dietary modifications (22.7%), and
      vitamin/mineral supplements (18.8%). Of the 207 patients who reported current or
      past CAM use for their glaucoma, 3 (1.4%) indicated that they used conventional
      glaucoma treatments < prescribed because of their CAM use. CONCLUSIONS:
      Approximately 1 in 9 glaucoma patients use CAM for their disease. Many of these
      patients do not disclose the use of CAM to their ophthalmologist, but the vast
      majority report that they still take conventional glaucoma medications as
      prescribed.

PMID- 21173702
TI  - Influence of cataract on time domain and spectral domain optical coherence
      tomography retinal nerve fiber layer measurements.
AB  - PURPOSE: To assess and compare the influence of cataract on measurements of
      retinal nerve fiber layer (RNFL) thickness by time domain (TD) optical coherence
      tomography (OCT) and spectral domain (SD) OCT. METHODS: Patients who underwent
      uncomplicated cataract surgery were consecutively enrolled in this study. The
      peripapillary RNFL thickness was measured before and 8 weeks after cataract
      surgery using TD-OCT and SD-OCT during the same visit. Changes in the RNFL
      thickness measurement and signal strength (SS) after cataract surgery were
      evaluated. RESULTS: A total of 54 patients (54 eyes) were included. After
      excluding 19 eyes owing to poor imaging or low SS (<5), scans of 35 eyes were
      included in the final analysis. A significant difference was identified between
      the preoperative and postoperative SS values using SD-OCT, but not TD-OCT
      (P=0.002 and 0.789, respectively). The changes in RNFL thickness after cataract
      surgery were more prominent and frequent for SD-OCT than TD-OCT. There was a
      significant correlation between change in preoperative RNFL thickness and SS
      changes for both TD-OCT (r=0.410, P<0.001) and SD-OCT (r=0.246, P=0.002).
      CONCLUSIONS: The presence of cataract significantly affects RNFL thickness
      measurements by SD-OCT and TD-OCT. SD-OCT, which demonstrated more consistent
      change of RNFL measurements after cataract extraction, is not necessarily
      associated with lower RNFL thickness measurement performance in cataract cases,
      as more participants with cataract were excluded because of poor image quality or
      low SS, which was more associated with TD-OCT than SD-OCT.

PMID- 21173703
TI  - Effects of static accommodation versus repeated accommodation on intraocular
      pressure.
AB  - PURPOSE: To compare the influences of static and repeated accommodation on the
      intraocular pressure (IOP). MATERIALS AND METHODS: A randomized, single-blind
      study was carried out on 33 healthy volunteers aged 20 to 29 years. Baseline IOP
      was measured after 10 minutes of viewing a distant target. Static accommodation
      was achieved by letting the volunteers focus for 3 minutes on a near target,
      which was individually adjusted to induce a 3 D accommodative demand. For the
      repeated accommodation, the volunteers were instructed to alternately focus on
      the near and distant target for 3 minutes. The accommodative responses were
      continuously monitored by an infrared photorefractor (PowerRef II), and Goldmann
      tonometry was performed immediately after the accommodative procedures. RESULTS:
      The IOP values (mean+/-SD) measured after static and repeated accommodation were
      13.4+/-2.4 mm Hg and 12.7+/-2.3 mm Hg, respectively (P=0.04). The IOP decreased
      significantly from baseline after both the static and repeated mode of
      accommodation with a mean change of -1.76+/-1.17 mm Hg (range, 0 to 4 mm Hg) and 
      2.06+/-1.48 mm Hg (range, 0 to 5 mm Hg), respectively. The IOP drop seemed to be
      greater after repeated accommodation compared with static accommodation; however,
      the difference was not statistically significant (P=0.35). CONCLUSIONS: The IOP
      was significantly reduced after both static and repeated accommodation. Compared
      with static accommodation, the repetitive mode of accommodation did not induce a
      statistically significant additional IOP drop, indicating that aqueous humor
      outflow is relatively unaffected by frequent ciliary muscle contractions.

PMID- 21173704
TI  - The 12-year incidence of glaucoma and glaucoma-related visual field loss in
      Italy: the Ponza eye study.
AB  - PURPOSE: To assess the 12-year incidence of glaucoma and glaucoma-related visual
      field loss in a population-based cohort study. PATIENTS: In 2000, we reexamined
      411 of the 581 survivors from the original Ponza eye study conducted in 1988.
      METHODS: Primary open-angle (POAG), primary angle-closure (PACG), and secondary
      [pseudoexfoliative (PEX)] glaucoma were diagnosed according to the 3-tiered
      system of evidence developed by the International Society of Geographical and
      Epidemiological Ophthalmology. Severity of glaucoma was classified according to
      the Bascom-Palmer system. Visual loss was defined according to World Health
      Organization guidelines. Relative risk ratios were calculated for several
      variables. RESULTS: The 12-year incidence of definite POAG was 3.8% (95%
      confidence intervals (CI), 2.3-6.2), that is, an average annual rate of 0.32%.
      Corresponding rates for PACG and PEX glaucoma were 0.5% (95% CI, 0.1-1.8) and
      0.8% (95% CI, 0.3-2.2), respectively. Half the incident glaucoma cases (45%) had
      not been diagnosed earlier. Fifty-five percent of the incident POAG eyes had
      Bascom-Palmer stage 1 or 2 disease and 40% of the incident PACG or PEX glaucoma
      eyes had stage 3 or 4 disease. Seven of 20 incident glaucoma cases presented with
      monocular or binocular visual loss because of advanced visual field loss.
      Significant risk factors for POAG included high myopia (>6.0 D), intraocular
      pressure >=22 mm Hg, and glaucoma family history. CONCLUSION: The average annual
      incidence of definite POAG in Ponzas lower than that reported in persons of
      African ancestry and higher than that observed in certain other white
      populations.

PMID- 21173705
TI  - Combined evaluation of frequency doubling technology perimetry and scanning laser
      ophthalmoscopy for glaucoma detection using automated classification.
AB  - PURPOSE: To develop a diagnostic setup with classification rules for combined
      analysis of morphology [Heidelberg Retina Tomograph (HRT)] and function
      [frequency doubling technology (FDT) perimetry] measurements. METHODS: We used 2
      independent case-control studies from the Erlangen eye department as learning and
      test data for automated classification using random forests. One eye of 334 open
      angle glaucoma patients and 254 controls entered the study. All individuals
      underwent HRT scanning tomography of the optic disc, FDT screening, conventional
      perimetry, and evaluation of fundus photographs. Random forests were learned on
      individuals of the Erlangen glaucoma registry (102 preperimetric patients, 130
      perimetric patients, 161 controls). The classification performances of random
      forests and built-in classifiers were examined by receiver operator
      characteristic analysis on an independent second cohort of individuals (47
      preperimetric patients, 55 perimetric patients, 93 controls). RESULTS: HRT
      measurements had a higher diagnostic power for early glaucomas and FDT perimetry
      for glaucoma patients with visual field loss. A combination of all parameters
      using automated classification was superior to single tests in comparison to the
      diagnostic instrument with the higher diagnostic power in the respective group.
      Highest sensitivities at a fixed specificity (95%) in the patients of the present
      test population were: HRT=32%, FDT=19%, combined analysis=47% in preperimetric
      patients and HRT=76%, FDT=89%, combined analysis=96% in perimetric patients.
      CONCLUSIONS: The feasibility of machine learning for medical diagnostic
      assistance could be demonstrated in patients from 2 independent study
      populations. A predictive model using automated classification is able to combine
      the advantages of morphology and function, resulting in a higher diagnostic power
      for glaucoma detection.

PMID- 21173706
TI  - IOP measured by dynamic contour tonometry correlates with IOP measured by
      Goldmann applanation tonometry and non-contact tonometry in Japanese individuals.
AB  - PURPOSE: The purpose of this study was threefold. We sought to compare the
      intraocular pressure (IOP) measured by dynamic contour tonometry (DCT) with that
      measured by Goldmann applanation tonometry (GAT) and noncontact tonometry (NCT).
      We also examined the influence of central corneal thickness (CCT) and corneal
      curvature radius (CCR) on the IOP measurements. Last, we investigated the factors
      that could affect the ocular pulse amplitude (OPA) measurements. METHODS: Seventy
      four patients with no history of intraocular surgery were enrolled in this study.
      We measured IOP by DCT, GAT, and NCT, and the CCT, CCR, and axial length (AL) in
      the right eye of each patient. We also measured OPA by DCT. We subsequently
      analyzed the correlation of IOP measurements between GAT and DCT and between NCT
      and DCT. We also examined the influence of CCT, CCR, and AL on IOP readings by
      the 3 tonometers. In addition, we investigated the factors that could affect the
      OPA measurements. RESULTS: The mean IOP measured by DCT was 2.8 mm Hg higher than
      that by GAT and 3.2 mm Hg higher than that by NCT. This difference was greater
      with thinner CCT in the lower IOP group than in the higher IOP group. IOP
      measurements by both GAT and NCT significantly correlated with CCT; however, IOP
      measurement by DCT did not correlate with CCT. No significant correlations were
      shown between the IOP measured by each of the 3 tonometers and either CCR or AL.
      OPA measurements positively correlated with age, IOP measurement by DCT, and
      pulse pressure. CONCLUSIONS: IOP measured by DCT correlates with IOP measured by
      GAT or NCT with a roughly 3.0 mm Hg higher value, and these differences were
      greater in the patients with a thinner CCT. IOP measurements by both GAT and NCT
      significantly correlated with CCT; however, IOP measurement by DCT did not
      correlate with CCT. Our findings also indicate that OPA measured using DCT shows
      a positive correlation with patient age, IOP measurement by DCT, and pulse
      pressure.

PMID- 21173707
TI  - Evaluation of peripapillary retinal nerve fiber layer thickness in myopic eyes by
      spectral-domain optical coherence tomography.
AB  - PURPOSE: To investigate the influence of myopia on peripapillary retinal nerve
      fiber layer (RNFL) thickness using Cirrus optical coherence tomography (OCT) in
      normal eyes. METHOD: Ninety-eight eyes of normal participants with various
      degrees of myopia were recruited in this study. The RNFL thickness was measured
      with high-definition (HD), spectral-domain Cirrus OCT (Cirrus HD-OCT; Carl Zeiss,
      Dublin, CA). The association between RNFL thickness and its spherical equivalent
      was evaluated with linear regression analysis. RESULTS: The RNFL thickness was
      119.2+/-16.8 MUm, 117.1+/-16.8 MUm, 75.9+/-16.1 MUm, and 64.9+/-9.8 MUm in the
      superior, inferior, temporal, and nasal quadrants, respectively, with an average
      thickness of 94.3+/-8.6 MUm. The mean RNFL thickness was thinner in highly and
      moderately myopic eyes (93+/-7.9 MUm and 92.6+/-7.7 MUm, respectively, P=0.0001)
      compared with low myopic eyes (102.2+/-9 MUm). A significant linear correlation
      was found between the spherical equivalent and the RNFL thickness in the superior
      (r=0.386, P=0.0001) and inferior quadrants (r=0.448, P=0.0001), and the average
      RNFL thickness (r=0.373, P=0.0001). CONCLUSIONS: Myopia can be a confounding
      factor in the assessment of RNFL thickness attributed to its influence on the
      RNFL thickness. Therefore, we recommend a careful interpretation of RNFL data,
      especially those obtained from eyes with moderate-to-high myopia.

PMID- 21173709
TI  - Trypan blue to assess Baerveldt tube patency after repair of its obstruction.
AB  - Tubal obstruction is a recognized complication of glaucoma drainage implants. In
      correcting a blocked tube, the surgeon may be uncertain about shunt competence
      even after removing the suspected cause of obstruction. We report the use of
      trypan blue dye to show tubal patency directly after the repair of a blocked
      Baerveldt tube.

PMID- 21173708
TI  - Clinical results of selective laser trabeculoplasty in open-angle glaucoma in
      Japanese eyes: comparison of 180 degree with 360 degree SLT.
AB  - PURPOSE: To evaluate the efficacy of selective laser trabeculoplasty (SLT) in the
      adjunctive treatment of medically diagnosed open-angle glaucoma and to compare
      the difference in intraocular pressure (IOP) lowering effects between 180-degree
      and 360-degree SLT. METHODS: This study is a retrospective consecutive chart
      review of open-angle glaucoma patients who had undergone first-time SLT from
      January of 2005 to July of 2007. All the patients had primary open-angle glaucoma
      or pseudoexfoliation glaucoma under medical treatment and followed for at least 3
      months after the procedure. The IOP reduction and treatment success were compared
      with the 2 treatment types. RESULTS: Twenty-nine patients underwent 180-degree
      SLT (35 eyes) and 25 patients underwent 360-degree SLT (34 eyes). The average
      follow-up was 19.5 months (range 3 to 36) for 180-degree group and 17.9 months
      (range 3 to 36) for 360-degree group. During the follow-up period, the 360-degree
      SLT group showed significantly lower posttreatment IOP at each follow-up point
      relative to pretreatment IOP, and its IOP reduction rate stayed statistically
      higher than the 180-degree group. We found a positive correlation between the
      pretreatment IOP and the IOP reduction rate for 360-degree SLT. The lower the
      pretreatment IOP was, the lower IOP reduction rate became. A Kaplan-Meier
      survival analysis showed higher success rates after 360-degree SLT than after 180
      degree SLT. CONCLUSIONS: The 360-degree SLT was shown to be more effective
      than180-degree SLT for intermediateterm reduction in IOP of Japanese patients
      with open-angle glaucoma as an adjunctive treatment protocol.

PMID- 21173710
TI  - CO2 laser-assisted sclerectomy surgery, part II: multicenter clinical preliminary
      study.
AB  - PURPOSE: To evaluate the efficacy of CO2 laser-assisted sclerectomy surgery
      (CLASS) in primary and pseudoexfoliative open-angle glaucoma. MATERIALS AND
      METHODS: Patients for primary filtration surgery underwent CLASS with a CO2 laser
      system (OT-134-IOPtiMate, IOPtima Ltd., Ramat Gan, Israel). This self-controlled
      system gradually ablates and removes scleral layers until percolating fluid
      absorbs the energy, attenuating further tissue ablation. Intraocular pressure
      (IOP) was measured at baseline, 1, 2, 4, and 6 weeks, and 3, 6, and 12 months,
      respectively. Complete success was defined as 5<=IOP<=18 mm Hg and 20% IOP
      reduction with no medication at a 12-month endpoint visit, and qualified success
      as the same IOP range with or without medication. RESULTS: Thirty of 37 patients
      completed 12 months of follow-up. Mitomycin C was used in 25 procedures (83.3%).
      The mean baseline IOP of 26.3+/-7.8 mm Hg (mean+/-SD) dropped to 14.4+/-3.4 and
      14.3+/-3.1 mm Hg at 6 and 12 months, respectively, with 42.4% and 40.7% IOP
      reduction at 6 and 12 months, respectively (P<0.001). Complete success was
      achieved by 76.7% and 60% of the patients at 6 and 12 months, respectively,
      whereas qualified success was achieved by 83.3% and 86.6% of the patients at 6
      and 12 months, respectively. Complications were mild and transitory with no
      sequela. CONCLUSIONS: Short-term and intermediate results suggest that CLASS may
      become a simple, safe, and effective means of choice for the treatment of open
      angle glaucoma.

PMID- 21173711
TI  - The role of tumor-infiltrating immune cells and chronic inflammation at the tumor
      site on cancer development, progression, and prognosis: emphasis on non-small
      cell lung cancer.
AB  - In addition to malignant neoplastic cells, cancer tissues also include immune
      cells, fibroblasts, and endothelial cells, including an abundant collection of
      growth factors, proangiogenic mediators, cytokines, chemokines, and components of
      the extracellular matrix. The main physiological function of the immune cells is
      to monitor tissue homeostasis, to protect against invading pathogens, and to
      eliminate transformed or damaged cells. Between immune cells and malignant cells
      in the tumor stroma, there is in fact a complex interaction which has significant
      prognostic relevance as the immune system has both tumor-promoting and 
      inhibiting roles. In non-small cell lung cancer (NSCLC), there is a marked
      infiltration of different types of immune cells, and the distribution, tissue
      localization, and cell types are significantly associated with progression and
      survival. Cancer immunotherapy has seen a significant progress during the last
      decade. An increased understanding of the mechanisms by which lung cancer cells
      escape the immune system, and the recognition of the key tumor antigens and
      immune system components in tumor ignorance have led to the development of
      several lung cancer vaccines. As the NSCLC prognosis in general is dismal, one
      may hope that future immunotherapy may be an effective adjunct to standard
      therapy, reversing immunologic tolerance in the tumor microenvironment. This
      review reports on the tumor stroma and in particular tumor-suppressing and 
      promoting roles of the immune system. Furthermore, it presents recent literature
      on relevant immune cell-related research in NSCLC.

PMID- 21173712
TI  - Alpha1-antitrypsin deficiency carriers, serum alpha 1-antitrypsin concentration,
      and non-small cell lung cancer survival.
AB  - INTRODUCTION: Although the association between alpha 1-antitrypsin deficiency
      (alpha1ATD) carriers and lung cancer risk has been found, the effects of
      alpha1ATD carriers and serum alpha 1-antitrypsin (alpha1AT) concentration on non
      small cell lung cancer (NSCLC) survival remained unclear. METHODS: Patients were
      selected from the Epidemiology and Genetics of Lung Cancer Study at Mayo Clinic
      with the criteria of (1) primary NSCLC diagnosis and (2) available alpha1ATD
      carrier status tested by isoelectric focusing serum alpha1AT concentration by
      immunonephelometry. The effects of carrier status and serum alpha1AT
      concentration on survival were evaluated by Cox proportional hazards models with
      (1) a landmark approach, where overall survival was defined from the time of
      blood draw to death from any cause and (2) included only patients with blood draw
      time before initial treatment. RESULTS: One thousand three hundred twenty-one
      patients were included in this study, with 179 alpha1ATD carriers and 1142
      noncarriers. No differences in overall survival by alpha1ATD carrier status were
      found (adjusted hazard ratio [AHR]: 0.98; 95% confidence interval [CI]: 0.82
      1.18). Nevertheless, serum alpha1AT concentration was significantly associated
      with survival among all patients in the landmark model (AHR per 50 mg/dl
      increments: 1.15; 95% CI: 1.10-1.20) and among patients whose blood was drawn for
      serum alpha1AT level assessment before any treatment (AHR per 50 mg/dl
      increments: 1.44; 95% CI: 1.21-1.71). CONCLUSIONS: Being an alpha1ATD carrier had
      no significant effect on NSCLC survival. The increased serum alpha1AT
      concentration was a poor prognosis marker for NSCLC, regardless of carrier
      status.

PMID- 21173713
TI  - Predictors and impact of second-line chemotherapy for advanced non-small cell
      lung cancer in the United States: real-world considerations for maintenance
      therapy.
AB  - INTRODUCTION: : Recent clinical trials incorporating maintenance chemotherapy
      into the initial treatment of advanced non-small cell lung cancer (NSCLC) have
      highlighted the benefits of exposing patients to second-line therapies. We,
      therefore, determined the predictors and impact of second-line chemotherapy
      administration in a contemporary, diverse NSCLC population. METHODS: : We
      performed a retrospective analysis of consecutive patients diagnosed with stage
      IV NSCLC from 2000 to 2007 at clinical facilities associated with the University
      of Texas Southwestern Medical Center. Demographic, disease, treatment, and
      outcome data were obtained from hospital tumor registries. The association
      between these variables was assessed using univariate analysis and multivariate
      logistic regression. RESULTS: : A total of 406 patients in this cohort received
      first-line chemotherapy and were included in the analysis. Mean age was 59 years,
      28% were women, and 59% were white. Among these patients, 197 (49%) received
      second-line chemotherapy. Among those patients who had not progressed after four
      to six cycles of first-line chemotherapy, 67% received second-line chemotherapy.
      Receipt of second-line chemotherapy was significantly associated with patient
      insurance type (p = 0.007), number of cycles of first-line chemotherapy (p <
      0.001), and receipt of prechemotherapy palliative radiation therapy (p = 0.005)
      but was not associated with patient age, gender, race, histology, or year of
      diagnosis. In a multivariate model, second-line chemotherapy administration
      remained associated with insurance type (p = 0.003), number of cycles of first
      line chemotherapy (p < 0.001), and receipt of prechemotherapy palliative
      radiation therapy (p = 0.008). The number of cycles of first-line chemotherapy
      and administration of second-line chemotherapy were associated with overall
      survival in both univariate and multivariate analyses. CONCLUSIONS: : In this
      unselected, contemporary, and diverse cohort of patients with advanced NSCLC, 67%
      of individuals whose disease had not progressed after four to six cycles of first
      line chemotherapy eventually received second-line chemotherapy. Markers of
      socioeconomic status, symptom burden, and response to and tolerance of first-line
      chemotherapy were associated with receipt of second-line chemotherapy. These
      factors may assist in the selection of patients most likely to benefit from
      maintenance chemotherapy.

PMID- 21173714
TI  - Radiologic features, staging, and operability of primary lung cancer in the
      Western cape, South Africa: a 1-year retrospective study.
AB  - INTRODUCTION: This retrospective study was performed to evaluate the radiologic
      features, staging, and resectability of lung cancer at the time of presentation
      in patients from the Western Cape of South Africa. METHOD: We included all
      patients with primary lung cancer reviewed during a 12-month period (January 2009
      to December 2009) who had a definite tissue diagnosis and whose staging computed
      tomography scans were available. Fifteen radiologic parameters were assessed.
      RESULTS: Data were complete in 204 patients. The proportion and median size of
      the various histologic subtypes were as follows: adenocarcinoma 53.9%, 53.4 mm;
      squamous cell 25.9%, 80.2 mm; small cell 14.2%, 80.8 mm; large cell 2.4%, 74.2
      mm; bronchioloalveolar carcinoma 1.5%, 50.0 mm; and others 2%, 57.6 mm,
      respectively. The overall median size of tumor was 61.5 mm. Tumors were located
      centrally in 43.6%, peripherally in 46.6%, indeterminate in 9.8%, mediastinal in
      11.3%, right lung in 53.4%, and in the left lung in 35.3%. Tuberculosis-related
      lung fibrosis was present in 16%, but only 5.4% patients had coexisting tumor and
      fibrosis at the same site. We observed no difference in the proportion of
      coexisting fibrosis between adenocarcinoma and squamous carcinoma. Only 16.2% of
      the patients were potential candidates for radical treatment, with an actual
      resection rate of 4.4%. CONCLUSIONS: In the Western Cape, adenocarcinoma is the
      commonest histologic subtype of bronchogenic carcinoma. Most patients present
      with late-stage primary tumors, and the percentage of patients with potentially
      resectable cancer is much lower than in Europe.

PMID- 21173715
TI  - The prognostic value of the simplified comorbidity score in the treatment of
      small cell lung carcinoma.
AB  - INTRODUCTION: Comorbidity may be an important prognostic factor in the treatment
      of small cell lung carcinoma (SCLC). This study aimed to investigate the
      prognostic values of simplified comorbidity score (SCS) in the treatment of
      patients with SCLC. METHODS: The patients with SCLC admitted to the National
      Taiwan University Hospital during the period from January 2000 to December 2006
      were included. The medical records were reviewed and analyzed. The SCS was used
      to evaluate comorbidities of the patients. A Cox proportional hazard model was
      used to calculate the hazard ratio (HR) and 95% confidence intervals (CIs) for
      age, gender, and factors significantly associated with survival identified in
      univariate analyses. RESULTS: A total of 172 patients were included; 56 patients
      had limited-stage disease and 116 had extensive-stage disease. Patients with an
      SCS more than 9 had shorter overall survival than those with SCS <= 9 both in
      limited-stage (372 days versus 581 days, p = 0.01) and extensive-stage disease
      (215 days versus 324 days, p = 0.001). Multivariate analysis indicated that SCS
      more than 9 was associated with a worse prognosis in patients with limited-stage
      disease (HR: 2.17, 95% CI: 1.12-4.21) and extensive-stage disease (HR: 1.74, 95%
      CI: 1.12-2.72), respectively. For patients with extensive-stage disease, SCS more
      than 9 was associated with poor treatment response (> 9 versus <= 9, disease
      response rate: 60.0% versus 82.4%, p = 0.02). CONCLUSIONS: The SCS may be an
      independent prognostic factor for patients with SCLC. Large-scale prospective
      studies may be required to validate the prognostic value of the SCS for SCLC.

PMID- 21173716
TI  - If given the choice...

PMID- 21173718
TI  - The gynecologic effects of lasofoxifene, an estrogen agonist/antagonist, in
      postmenopausal women.

PMID- 21173719
TI  - Comparing the prevalence of chlamydial infection across populations--what is
      appropriate?

PMID- 21173720
TI  - Chlamydia trachomatis age-specific prevalence in women who used an internet-based
      self-screening program compared to women who were screened in family planning
      clinics.
AB  - OBJECTIVES: To determine whether women who collect self-collected vaginal swabs
      at home demonstrated a higher positivity of Chlamydia trachomatis than women in
      family planning clinics. METHODS: Collection kits for vaginal swabs were internet
      requested, collected at home, and mailed to a laboratory for testing;
      questionnaires were completed about acceptability and sexual risk history.
      Infected women received treatment at participating clinics. Age-specific
      prevalences were compared to those from family planning clinics. RESULTS:
      Chlamydia positivity was 10.3% for 1171 females mailing swabs; prevalences ranged
      from 3.3% to 5.5% in family planning. Positivity for internet age groups was much
      higher than those for family planning age groups. The positivity for internet
      participants ranged from a low of 4.4% in Baltimore in 2005 to a high of 15.2%
      Baltimore in 2007. Family planning clinic prevalence in Baltimore and Maryland
      ranged from a low of 3.3% in Baltimore in 2006 to a high of 5.5% in Baltimore in
      2008. The median age for all years for internet users in Baltimore and Maryland
      combined was 23 years; the median age for all years for attendees to family
      planning clinics who had chlamydia testing performed was 23 years. CONCLUSIONS:
      Internet recruited women demonstrated higher positivity of chlamydia than those
      in family planning, providing new options for chlamydia screening programs.

PMID- 21173721
TI  - Reaching patients and their partners through mobile: text messaging for case
      management and partner notification.

PMID- 21173722
TI  - A paradox: overscreening of older women for Chlamydia while too few younger women
      are being tested.

PMID- 21173723
TI  - Frameshifting in the p6 cDNA phage display system.
AB  - Phage display is a powerful technique that enables easy identification of targets
      for any type of ligand. Targets are displayed at the phage surface as a fusion
      protein to one of the phage coat proteins. By means of a repeated process of
      affinity selection on a ligand, specific enrichment of displayed targets will
      occur. In our studies using C-terminal display of cDNA fragments to phage coat
      protein p6, we noticed the occasional enrichment of targets that do not contain
      an open reading frame. This event has previously been described in other phage
      display studies using N-terminal display of targets to phage coat proteins and
      was due to uncommon translational events like frameshifting. The aim of this
      study was to examine if C-terminal display of targets to p6 is also subjected to
      frameshifting. To this end, an enriched target not containing an open reading
      frame was selected and an E-tag was coupled at the C-terminus in order to measure
      target display at the surface of the phage. The tagged construct was subsequently
      expressed in 3 different reading frames and display of both target and E-tag
      measured to detect the occurrence of frameshifting. As a result, we were able to
      demonstrate display of the target both in the 0 and in the +1 reading frame
      indicating that frameshifting can also take place when C-terminal fusion to minor
      coat protein p6 is applied.

PMID- 21173724
TI  - Insecticidal activity of essential oil of Carum Carvi fruits from China and its
      main components against two grain storage insects.
AB  - During our screening program for agrochemicals from Chinese medicinal herbs and
      wild plants, the essential oil of Carum carvi fruits was found to possess strong
      contact toxicity against Sitophilus zeamais and Tribolium castaneum adults, with
      LD50 values of 3.07 and 3.29 MUg/adult, respectively, and also showed strong
      fumigant toxicity against the two grain storage insects with LC50 values of 3.37
      and 2.53 mg/L, respectively. The essential oil obtained by hydrodistillation was
      investigated by GC and GC-MS. The main components of the essential oil were
      identified to be (R)-carvone (37.98%) and D-limonene (26.55%) followed by alpha
      pinene (5.21), cis-carveol (5.01%) and beta-myrcene (4.67%). (R)-Carvone and D
      limonene were separated and purified by silica gel column chromatography and
      preparative thin layer chromatography, and further identified by means of
      physicochemical and spectrometric analysis. (R)-Carvone and D-limonene showed
      strong contact toxicity against S. zeamais (LD50 = 2.79 and 29.86 MUg/adult) and
      T. castaneum (LD50 = 2.64 and 20.14 MUg/adult). (R)-Carvone and D-limonene also
      possessed strong fumigant toxicity against S. zeamais (LC50 = 2.76 and 48.18
      mg/L) and T. castaneum adults (LC50 = 1.96 and 19.10 mg/L).

PMID- 21173725
TI  - Synthesis of 2-(4,6-dimethoxy-1,3,5-triazin-2-yloxyimino) derivatives:
      application in solution peptide synthesis.
AB  - A new class of 1,3,5-triazinyloxyimino derivatives were prepared, characterized
      and tested for reactivity in solution peptide synthesis. The new
      triazinyloxyimino derivatives failed to activate the carboxyl group during
      formation of peptide bonds, but gave the corresponding N-triazinyl amino acid
      derivatives as a major product. The oxyma (ethyl 2-cyano-2-(hydroxyimino)acetate)
      uronium salt was superior to other uronium salts in terms of racemization, while
      2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT, 9) gave the best results.

PMID- 21173726
TI  - Facile and convenient synthesis of new thieno[2,3-b]-thiophene derivatives.
AB  - A facile and convenient synthesis of bis(2-(1H-benzo[d]imidazol-2(3H)-ylidene)-3
      oxopropanenitrile), bis((3-amino-5-(methylthio)-1H-pyrazol-4-yl)methanone) and
      bis(2-thioxo-1,2-dihydropyrimidine-5-carbonitrile) derivatives incorporating a
      thieno- [2,3-b]thiophene moiety via versatile, readily accessible diethyl 3,4
      dimethylthieno-[2,3-b]thiophene-2,5-dicarboxylate is described.

PMID- 21173727
TI  - Synthesis and antitumor activity of 3-methyl-4-oxo-3,4-dihydroimidazo [5,1
      d][1,2,3,5]tetrazine-8-carboxylates and -carboxamides.
AB  - Seventeen novel 3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8
      carboxylate and -carboxamide derivatives were synthesized and evaluated for their
      growth inhibition in seven human solid tumor and a human leukemia HL-60 cell
      lines. Compound IVa showed more activity than the other compounds and the
      positive control temozolomide. In the presence of 40 MUg/mL of IVa, the survival
      rate of all tested tumor cells was less than 10%. Esters displayed more potent
      antitumour activity than amides and temozolomide against HL-60 cells. These
      compounds also exhibited considerably enhanced water-solubility.

PMID- 21173728
TI  - Preoperative withdrawal of antiplatelet treatment in lower limb vascular patients
      prior to surgical management under epidural or spinal anaesthesia: an evidence
      based approach and systematic review.
AB  - Antiplatelet drugs given to high risk patients for secondary prevention of
      cardiovascular disease are frequently withdrawn prior to surgical or diagnostic
      procedures to reduce bleeding complications. This is also the case for many
      patients undergoing lower limb vascular surgery via spinal or epidural
      anaesthesia. The aim of this study is to corroborate the clinician's decision for
      discontinuing or continuing the anti-platelet treatment in these patients
      perioperatively. We screened MEDLINE and Scopus (January 1980 - July 2007) with
      additional manual cross-referencing for clinical studies, surveys on the opinions
      of doctors and guidelines according to Evidence Based Medicine rules. One
      randomized controlled trial, 2 meta-analyses, 1 prospective and 4 retrospective
      studies as well as 6 esteemed medical societies'" guidelines all conclude that
      there is no justification for the discontinuation of aspirin and NSAIDs prior to
      neuraxial anesthesia. However, for other antiplatelet drugs like ticlopidine,
      clopidogrel, abciximab, eptifabatide and tirofiban not enough data exist to
      support their continuation through the procedure. Therefore, their preoperative
      withdrawal is suggested 8 hours to 14 days prior, accordingly. The existing
      evidence does not justify the discontinuation of aspirin and NSAIDs before the
      intended procedure. Anesthesiologists and surgeons should be aware of the
      cardiovascular risks of withdrawal versus the non - evidence based benefit in
      hemorrhage complications.

PMID- 21173729
TI  - ABI derived from the highest and lowest ankle pressure. What is the difference?
AB  - AIM: Different modes of ankle-brachial -index (ABI) calculation lead to different
      information. We looked for the peripheral arterial disease (PAD) prevalence
      estimated from ABI-high and ABI-low and analysed the effect of age and classical
      risk factors. METHODS: Based on the Arteriomobil Project data, ABI was calculated
      considering the lowest of the four ankle artery pressures (ABI-low) or the higher
      ankle artery pressure of each leg (ABI-high), respectively. ABI <0.9 were defined
      to prove PAD. RESULTS: Prevalence of PAD estimated using ABI-low was much higher
      than those using ABI- high (15.7% vs. 8.0%). Thus 8% of men and 7.5% of women
      suspected for PAD were not detected if prevalence rates are based on ABI-high
      alone. Estimating PAD prevalence only by measuring posterior tibial artery (ATP)
      pressure, prevalence rates were lowest with 2.4% for the left and 2.7% for the
      right ATP. Estimating PAD prevalence only by measuring anterior tibial artery
      pressure, prevalence rates were slightly higher, but still low. ABI-high
      systematically shows lower prevalence rates compared to ABI-low without
      divergence of the prevalence rates with increasing age. This parallelism of the
      curves remained unchanged when prevalence rates were separated for self-reported
      risk-factors; smoking, hypertension, hypercholesterolemia and diabetes.
      CONCLUSION: The presented analysis of the Arteriomobil Project data support the
      hypothesis that the differences in prevalence rates estimated from ABI-high and
      ABI-low are mainly determined by anatomic variations of the plantar arch.
      Additional angiographic controlled studies are necessary to prove this
      hypothesis.

PMID- 21173730
TI  - Trace elements and toxic heavy metals play a role in Buerger disease and
      atherosclerotic peripheral arterial occlusive disease.
AB  - AIM: The aim of the present study was to define the roles of trace elements and
      toxic heavy metals in Buerger disease and atherosclerotic peripheral arterial
      occlusive disease (PAOD). METHODS: Seventy-five subjects who were identical in
      demographic charecteristics were selected for the study; 25 with Buerger disease,
      25 with PAOD, 25 healthy volunteers. Serum selenium (Se), zinc (Zn), copper (Cu),
      iron (Fe),whole blood cadmium (Cd) and lead (Pb), erythrocyte glutathione (GSH),
      erythrocyte glutathione peroxidase (GSH-Px), erythrocyte and plasma
      malondialdehyde (MDA) levels were measured. RESULTS: Serum Se and Zn levels were
      significantly low in patients with Buerger disease compared to patients with PAOD
      and controls (P<0.001 and P<0.001 respectively). Serum levels of Fe and Zn were
      also significantly low in patients with PAOD compared to controls (p<0.001 and
      p<0.05 respectively). In contrast, Cu and Pb levels in Buerger disease group were
      significantly high compared to PAOD and control groups (P<0.001 and P<0.001
      respectively). Erythrocyte GSH and GSH-Px levels were significantly lower in
      patients with Buerger disease compared to patients with PAOD and controls
      (P<0.001 and P<0.001 respectively), while erythrocyte and plasma MDA levels were
      significantly higher (P<0.001 and P<0.001 respectively). CONCLUSION: It can be
      concluded that the levels of trace elments and toxic heavy metals and oxidative
      stress influence the disease process in Buerger disease more than PAOD.

PMID- 21173731
TI  - IL-6, TNF-alpha, IL-1-beta arterial wall expression is independent of serum
      concentration in patients sustaining primary or secondary open vascular
      reconstructions.
AB  - AIM: The aim of this study was to assess morphological and immunohistochemical
      differences in arterial wall inflammation during primary and secondary vascular
      reconstructions. METHODS: Forty patients with lower extremities ischemia
      underwent vascular reconstruction: Group I included patients undergoing primary
      vascular reconstruction with 25 minor arterial reconstructive procedures; Group
      II included patients undergoing secondary reconstruction due to limb ischemia
      after at least 12 months since first operation (15). Immunohistochemical
      expression of IL-1-BETA,IL-6,and TNF-alpha in arterial wall was correlated with
      serum concentration. RESULTS: No differences were observed in IL-1-beta, IL-6,
      TNF-alpha expression among groups (P=0.06, P=0.13, P=0.9). Cytokines expression
      was not accompanied by the growth of its serum concentrations (P=0.8, P=0.9). IL
      6 serum concentration depended on the degree of limb ischemia and was very high
      in case of critical limb ischemia (P=0.006). Arterial morphology was comparable
      among the groups. CONCLUSION: IL-6, IL-1-BETA, TNF-alpha expression in the
      arterial wall is comparable in primary and secondary lesions. Serum
      concentrations of IL-6, IL-1-BETA, TNF-alpha are independent of its arterial wall
      expression.

PMID- 21173732
TI  - Age-related changes in apoptosis and expressions of intercellular adhesion
      molecule-1 and vascular endothelial growth factor receptor type 2 in the wall of
      varicose veins.
AB  - AIM: Dysregulated apoptosis in the venous wall is believed to play important role
      in the onset and progression of human primary varicose veins. The aim of our
      study was to in situ investigate the apoptosis of endothelial cells (EC) and
      smooth muscle cells (SMC) together with the expression of intercellular adhesion
      molecule-1 (ICAM-1) and vascular endothelial growth factor receptor type 2 (VEGF
      R2) in the varicose veins of women of different age groups. METHODS: Women (n=34)
      undergoing surgery for varicosities were divided into three groups: Group I
      (younger than 35 year); Group II (36-50 years); Group III (older than 50 years).
      Apoptotic EC and SMC were determined by the TUNEL method. ICAM-1 and VEGF R2 were
      detected immunohistochemically in the endothelium, the subendothelial layer, the
      media and the adventitia. RESULTS: The number of apoptotic EC and SMC rose in the
      group of older patients (Group III vs Group I; P<0.01 and P<0.05, respectively).
      In the same group ICAM-1 immunostaining was increased in the endothelium, but
      decreased in the media and the adventitia, while VEGF R2 staining was increased
      in the endothelium, the subendothelial layer and the media, but decreased in the
      adventitia. CONCLUSION: In conclusion, our study demonstrated that apoptosis of
      EC and SMC increase in varicose veins with advancing age and age-related
      differences exist also in the expression of ICAM-1 and VEGF R2 in the wall of
      varicose veins of women.

PMID- 21173733
TI  - Efficacy and safety of long-term ezetimibe/simvastatin treatment in patients with
      familial hypercholesterolemia.
AB  - AIM: Patients with heterozygous familial hypercholesterolemia (FH) have an
      increased risk of premature myocardial infarction, stroke, and surgical
      revascularization, and an increased rate of progression of carotid intima-media
      thickness (IMT). The most commonly used drugs for cholesterol lowering, statins,
      have a limited action in these patients. Ezetimibe, a novel compound, selectively
      inhibits cholesterol uptake and when associated with statins has an additional
      low-density lipoprotein cholesterol (LDL-C) reducing effect. The aim of this
      study is to evaluate the effects of long-term combined Ezetimibe/Simvastatin
      (EZE/SIMVA) therapy (30 months) on the lipidic pattern, inflammatory markers, and
      carotid IMT in patients with FH subdivided into two groups: one with a history of
      acute myocardial infarction (IMA) and the other with carotid atherosclerotic
      plaques but no history of cardiovascular events. METHODS: All patients enrolled
      in this study (group A: patients with a history of IMA; group B, patients with
      carotid lesions but no history of cardiovascular events) were submitted to a 6
      week period of isocaloric diet and to a 4-week lipid-lowering wash-out period
      before study entry. After the wash-out period at baseline (time 0) and then every
      two months total cholesterol, triglycerides, high-density lipoprotein cholesterol
      (HDL-C), and apolipoprotein B and A1 were determined. LDL-C levels were
      calculated. Fibrinogen and hs-CRP at baseline and at 6, 18, and 30 months were
      determined. All patients were submitted to an ultrasonographic evaluation of the
      carotid intima-media thickness at baseline, 18 and 30 months. The scheduled
      duration time of the study was 30 months. At the beginning of the study all
      patients were assigned to receive the combined EZE/SIMVA treatment 10/20 mg per
      day. After two months, patients who had not reached the respective LDL-C targets
      proposed by NCEP ATPIII (<70 mg/dL for patients with a history of IMA and <100
      mg/dL for patients with carotid lesions) were assigned to receive EZE/SIMVA 10/40
      mg per day and, after four months, patients who had not reached the respective
      LDL-C targets were assigned to receive EZE/SIMVA 10/80 mg per day. RESULTS: At
      the end-point, significant reductions (P<0.001) of about 70% in LDL-C, of 57% in
      total cholesterol (TC), of 46% in Apo-B, and of 46% in hs-C-reactive protein (hs
      CRP) were observed in both groups compared to baseline. Also, triglyceride and
      fibrinogen levels were significantly (P<0.01) reduced, respectively by 26% and
      15% compared to baseline. The EZE/SIMVA association resulted in significant
      increases in HDL-C (P<0.01) of 11% and in Apo-A1 (P<0.05) by 9% and in
      significant (P<0.001) reductions of the mean of the carotid IMT in both groups.
      The EZE/SIMVA treatment was generally well-tolerated, with a safety profile on
      laboratory parameters. During the 30-month scheduled period of the study, no
      patient in either group presented any further cardiovascular events. CONCLUSION:
      In patients with FH, combined EZE/SIMVA treatment resulted in a significant LDL-C
      lowering, achieving the goals proposed by NCEP ATP III, in a significant
      improvement of all the lipidic and inflammatory patterns, and above all in a
      progressive decrease of the carotid IMT. Although the results of ongoing
      randomized controlled trials are required before making any definitive
      conclusions, our results support the hypothesis of stabilizing effect of
      EZE/SIMVA on the atherosclerotic disease both in primary and in secondary
      prevention.

PMID- 21173735
TI  - Phlebology training curriculum. A consensus document of the International Union
      of Phlebology (UIP)-2010.

PMID- 21173734
TI  - Quality of life improvement in Latin American patients suffering from chronic
      venous disorder using a combination of Ruscus aculeatus and hesperidin methyl
      chalcone and ascorbic acid (quality study).
AB  - AIM: The present study assessed the effect of Ruscus aculeatus, hesperidin methyl
      chalcone and ascorbic acid (HMC-AA), in the treatment of chronic venous disorders
      (CVD) in Latin American patients. METHODS: This study is an observational, single
      arm, multicentric and prospective trial. Patients suffering from CVD and
      belonging to C0s-C3 Clinical Etiological Anatomical and Physiopathological (CEAP)
      classes were included. Patient profiles, risk factors, clinical symptomatology
      and quality of life (QoL) assessed by SF-12 and CIVIQ questionnaires were
      evaluated at inclusion and after 12-week treatment. RESULTS: The main factors
      influencing the previous management of patients were age, gender, body mass index
      (BMI), familial history, physical activity, exposure to heat, heavy loads
      lifting, profession and clinical characteristics. All clinical symptoms
      significantly improved with treatment and, as BMI and CEAP classes increased.
      Ankle circumferences decreased over time, correlating with BMI and CEAP classes.
      The physical and psychological dimensions of the SF-12 score significantly
      increased over time and improved within each CEAP class. The CIVIQ score
      significantly improved over time, correlating with age and CEAP classes.
      CONCLUSION: A 12-week treatment with Ruscus aculeatus HMC-AA showed a significant
      decrease in the clinical symptoms and a significant improvement in the QoL of
      patients with CVD.

PMID- 21173736
TI  - Cryoglobulinemia manifested by gangraene of almost all fingers and toes.
AB  - Cryoglobulinemia is a rather rare condition accompanying quite a broad spectrum
      of different states and diseases. Mixed or polyclonal cryoglobulins can be seen
      in patients with autoimmune disorders, chronic infections and lymphoproliferative
      disorders. Monoclonal cryoglobulins are often revealed in patients with multiple
      myeloma or Waldenstrom's macroglobulinemia. Cryoglobulinemia is in most cases
      asymptomatic. Cryoglobulinemic vasculitis is an immune complex-mediated systemic
      disorder involving mostly small, but sometimes also larger vessels. In this
      report, we describe a case of a patient presented with gangrene of almost all
      fingers and toes, who was finally diagnosed and treated as cryoglobulinemic
      vasculitis due to multiple myeloma.

PMID- 21173737
TI  - Endovascular graft bail-out post reconstruction of popliteal artery injury. First
      case report.
AB  - A male patient who sustained a blunt trauma to the right knee and chest resulting
      in posterior dislocation of the knee joint and avulsion injury to the right
      popliteal artery (segments II and III) had a vascular repair by interposition
      saphenous vein graft. Postoperatively an episode of hypotension resulted in
      thrombotic occlusion of the graft and acute limb ischemia. Graft and distal
      thrombectomy, though successful, resulted in a stenotic segment with two
      perforations. To shorten the operating time this was managed by Viabahn
      Endoprothesis stent-graft through both native popliteal artery and vein graft.
      Immediate regain of pedal pulses was achieved, and at 6 months follow up Viabahn
      endograft is still patent, foot well perfused with normal pedal pulses and
      patient fully active. In complicated popliteal artery injuries, with complex time
      consuming revascularization procedures, an endovascular graft as a back up or
      bail-out technique might be a valid option in some selected cases with high
      anesthetic risk, to shorten operating time. In this context Viabahn
      endoprosthesis seems to be both efficient and durable on the short term.

PMID- 21173738
TI  - The significance of 1793G>A polymorphism in MTHFR gene in women with first
      trimester recurrent miscarriages.
AB  - BACKGROUND: Recurrent miscarriages (RM) are significant social and clinical
      problem. One of suggested reason of RM is hyperhomocysteinemia. Polymorphic genes
      involved in homocysteine and folate metabolism, including 5,10
      methylenetetrahydrofolate reductase (MTHFR) gene, are considered as an important
      risk factors for homocysteine accumulation and modulator of RM susceptibility.
      Therefore the aim of this study was to evaluate the frequency of MTHFR
      polymorphisms (677C>T, 1298A>C, and 1793G>A) in women with recurrent
      miscarriages. MATERIAL AND METHODS: We have analyzed 104 Polish women with a
      history of 3 or more unexplained recurrent miscarriages in the first pregnancy
      trimester (6-13 gestation week). The control group consisted of 169 women without
      obstetrical complication, any history of miscarriage and with at least one live
      birth in anamnesis. The investigated polymorphisms were determined by PCR/RFLP
      methods. RESULTS: For MTHFR 1793G>A polymorphism we have observed significant
      overrepresentation of heterozygotic GA genotypes in RM group (15.38% vs. 4.14% in
      the controls, OR=4.21, p=0.003). For 677C>T and 1298A>C we have shown lack of
      significant association with RM. Nevertheless, such significant association was
      observed if more than one mutated MTHFR variant was present in one patient.
      CONCLUSIONS: Our research indicate the possible role of MTHFR 1793G>A
      polymorphism in pathogenesis of RM. The noticed tendency to more frequent
      occurrence of haplotypes of MTHFR gene including two or three mutated alleles
      showed the possibility of summarized amplification of these variants effect
      influencing RM susceptibility.

PMID- 21173739
TI  - The role of the vagus nerve in depression.
AB  - The etiopathogenesis of depression is a highly complex process characterized by
      several neurobiological alterations including decreased monoamine
      neurotransmission in the brain, dysregulated hypothalamic-pituitary-adrenal axis
      activity, decreased neuronal plasticity, and chronic inflammation in the brain
      and peripheral tissues. Experimental and clinical studies indicate that the vagus
      nerve may influence these processes. The importance of the vagus nerve in the
      etiopathogenesis of depression is further supported by its involvement in the
      induction of sickness behavior, as well as by clinical studies confirming a
      beneficial effect of vagus nerve stimulation in depressed patients. The aim of
      this article is to describe current knowledge of afferent and efferent vagal
      pathways role in the development and progression of depression.

PMID- 21173740
TI  - The mild stress of chronic prenatal injections may have additive effects on drugs
      administered during pregnancy to alter brain sexual differentiation.
AB  - OBJECTIVE: In order to clarify the effect of the prenatal (PN) treatment of the
      drug 1,4,6-androstatriene-3,17-dione (ATD) which blocks the conversion of
      testosterone into estradiol on male sexual behavior of the rats offsprings, from
      the effect of the mild stress induced by the PN administration of the Propylene
      glycol (PG), the vehicle used to dissolve ATD. METHODS: Pregnant Wistar rats were
      divided into three groups. The CON group did not receive any kind of treatment.
      The other two groups (PG and ATD) were injected i.p. during gestation (days 11
      22) with 0 and 5 mg of ATD, dissolved in 0.1 ml of PG, respectively, doses
      reported by other authors. Sexual performance of the male pups was analyzed three
      months later in four successive tests. RESULTS: In the first sexual test of these
      naive rats, the percentage of males mounting, intromitting, ejaculating and the
      ejaculation frequency of the ATD group decreased significantly in comparison with
      the CON group. Also in the first and 4th tests, mounting, intromission and
      ejaculation latencies, as in the post-ejaculatory refractory period, ATD group,
      was significantly longer in comparison with the CON group. PG males showed a male
      sexual behavior (MSB) similar to that observed in the ATD group, but the
      differences did not reach statistical significance when they were compared with
      the CON group. CONCLUSION: We considered that the PN stress induced by the daily
      administration of PG and ATD, results in a slower execution of the MSB in both
      groups and avoid distinguish the effect of the ATD. Then chronic PN injections,
      as a route of administration, could act as mild stressor and may have additive
      effects on drugs affecting brain sexual differentiation.

PMID- 21173741
TI  - Serum resistin is related to plasma HDL cholesterol and inversely correlated with
      LDL cholesterol in diabetic and obese humans.
AB  - OBJECTIVES: Plasma cholesterol, triglycerides and serum resisistin may all be
      influenced by diabetes and obesity, but their associations remain unclear.
      Therefore, we put forward a hypothesis that serum lipids might be parallel to
      resistin, as they all reflect the metabolic status of obese humans. DESIGN AND
      SETTING: We measured the concentrations of resistin, total cholesterol (TC), HDL
      cholesterol (HDL-C), LDL-cholesterol (LDL-C) and triglycerides (TG) in 134 obese
      non-diabetic (73 women and 61 men) and 65 obese diabetic (33 women, 32 men)
      humans, and examined their interrelations. Obesity was defined according to the
      WHO criterion (BMI, >= 30 kg/m2) The presence of diabetes was the only
      differentiating factor between two groups of frankly obese humans. RESULTS: Non
      diabetic vs. diabetic, median and interquartile range, respectively: resistin
      (ng/mL) 26.08, 16.09 vs. 22.37, 14.54, p=0.736; TC (mmol/L) 5.02, 1.39 vs. 5.16,
      1.56, p=0.374; HDL-C (mmol/L): 1.10, 0.41 vs. 1.02, 0.47 p<0.05; LDL-C (mmol/L):
      3.00, 1.05 vs. 3.00, 1.30 p=0.978; TG (mmol/L) 1.70, 1.43 vs.1.95, 1.81 p<0.05.
      To investigate the interrelations between resistin and lipids, a simple
      regression analysis was used, and the results were for resistin & TC, HDL-C, LDL
      C, and TG, respectively: in the whole cohort r=-0.1364, p=0.0670, r=0.1514,
      p=0.0437, r=-0.2573, p=0.0006, r=0.0434, p=0.5597; in non-diabetics: r=-0.2067,
      p=0.0213, r=0.1023, p=0.2621, r=-0.2399, p=0.0083 and r=0.0288, p=0.7497; in
      diabetics r=0.0280, p=0.8360, r=0.2267, p=0.0929, r=-0.2933, p=0.0298, r=0.1349,
      p=0.3127. CONCLUSIONS: In diabetic and non-diabetic subjects the atherogenic LDL
      cholesterol shows an inverse correlation with resistin, whereas the protective
      anti-atherosclerotic HDL cholesterol is positively correlated with resistin.

PMID- 21173742
TI  - Quality of life and exercise capacity in obesity and growth hormone deficiency.
AB  - OBJECTIVES: A great similarity exists between growth hormone (GH) deficiency and
      obesity in terms of disturbances of organ morphology and function. The aim of the
      study was to compare health-related quality of life (HR-QoL) as well as exercise
      capacity and its subjective assessment in adult patients with GH deficiency and
      in adult patients with obesity. METHODS: Ten (10) GH-deficient, thirty (30)
      obese, and thirty (30) healthy subjects participated in the study. HR-QoL
      comprised two parameters: QoL measured by using the Quality of Life Assessment of
      Growth Hormone Deficiency in Adults (QoL-AGHDA) questionnaire, and subjective
      evaluation of general health state by using the Visual Analogue Scale. The
      exercise capacity was determined in Six Minute Walking Test and it was
      subjectively assessed by Borg Scale for Rating Perceived Exertion and the
      modified Medical Research Council scale. RESULTS: Decreased HR-QoL (both
      parameters) was observed in both GH-deficient and obese patients, with that
      effect being much more pronounced in the former group. Both, GH-deficient and
      obese patients, revealed decreased exercise capacity, which was also subjectively
      assessed as decreased, especially by GH-deficient patients. Positive
      relationships between HR-QoL and exercise capacity or its subjective assessment,
      observed in healthy subjects, partially lost their significance in obese, whereas
      they completely disappeared in GH-deficient subjects. CONCLUSION: A decrease in
      HR-QoL is more pronounced in GH-deficient than in obese patients, whereas
      exercise capacity is unfavourably affected by both disorder to a similar extent,
      with the lack of clear relationship between these two parameters especially in GH
      deficient patients.

PMID- 21173743
TI  - Pituitary abscess: a case report.
AB  - OBJECTIVES: Pituitary abscess is rare disease and the correct diagnosis is
      difficult because there are non-specific symptoms and it is often radiologically
      indistinguishable from other pituitary lesions. CASE PRESENTATION: We present one
      case of pituitary abscess that constitute 0.15% of all pituitary adenomas
      operated in our department in the 20 years. A 49-year-old woman presented with a
      history of 10 months bifrontal headache. The MRI showed cystic intra and
      suprasellar mass with ring enhancement after contrast injection. During
      transsphenoidal surgery, copious yellowish pus was found. Antibiotic therapy was
      performed. Histological study of the cyst wall confirmed the diagnosis of
      pituitary abscess. CONCLUSION: Pituitary abscess should be considered in the
      differential diagnosis of all other cyst mass in patients with diabetes
      insipidus.

PMID- 21173744
TI  - Oxytocin and carbetocin ameliorating effects on restraint stress-induced short-
      and long-term behavioral changes in rats.
AB  - OBJECTIVES: Carbetocin (CBT), an oxytocin (OXY) analog, was designed to exert
      prolonged peripheral actions. It has also been proposed as potential therapeutic
      mean in certain psychiatric disorders where OXY role has been implicated. This
      study examined the effects of both peptides on behavior of naive and restraint
      stress exposed rats in the open field (OF) and elevated plus maze (EPM) tests.
      METHODS: Spontaneous behavior in the OF and EPM was measured in Wistar rats after
      intraperitoneal (i.p.) application of OXY or CBT and/or repeated restraint
      stress. Behavioral parameters were recorded and subsequently elaborated by an
      automated activity monitoring system (AnyMaze, Stoelting, U.S.A.). Changes in the
      total movement distance (TMD) and movement in the center area (CMD) were
      postulated as indicators of the anxiety level. RESULTS: OXY (0.05 mg/kg) and CBT
      (0.3 mg/kg) increased TMD but not CMD 60 min after the i.p. treatment; the
      increased locomotion/exploration indicate participation of arousal/vigilance.
      Daily stress exposures for three consecutive days, followed by behavioral tests,
      reduced locomotion of rats in OF and EPM tests; OXY and CBT partly prevented
      these effects. Five days after the last stress, rats exhibited an increase of
      both TMD and CMD in the OF. CBT but not OXY prevented these long-term post-stress
      changes. In the EPM the stressed rats exhibited an increase in time spent in open
      arms; CBT accelerated this time development. Similar prevention of stress
      behavioral sequel in OF were obtained in study when stress and peptides were
      applied for three consecutive days but behavioral testing was postponed for
      several days to determine the long-lasting effects. CBT reduced the developed
      locomotor enhancement (6-11 days post-stress) irrespectively whether injected
      before or after stress. CONCLUSIONS: Repeated restraint stress exposure produced
      acute and persisting effects on Wistar rat behavior in the OF and EPM tests. CBT
      either injected before or after stress practically abolished the developed
      changes in the mobility parameters. The CBT effectiveness to ameliorate the late
      post-stress behavioral alteration supports the notion of its therapeutic
      potential in psychiatric disorders in which the role of OXY has been implicated.

PMID- 21173745
TI  - Obesity accompanies narcolepsy with cataplexy but not narcolepsy without
      cataplexy.
AB  - BACKGROUND: Narcolepsy with cataplexy (NC) differs from narcolepsy without
      cataplexy (NwoC) in the cerebrospinal fluid levels of hypocretin. Since
      hypocretin is known to regulate not only wakefulness but also eating behaviour,
      we decided to compare the two entities for body mass index (BMI) and the presence
      of obesity. METHODS: Clinical data on patients with NC and NwoC was studied and
      examined, including nocturnal polysomnography and the Multiple Sleep Latency Test
      (MSLT). The results were rated against a group of age- and sex-matched healthy
      controls. RESULTS: The BMI in NC (29.1+/-SD=5.8) was significantly higher than in
      NwoC (25.4+/-4.4) or in the controls (25.8+/-3.9) (p<0.001, F=17.4, df= 323),
      while no difference in BMI was found between NwoC and the controls. The
      proportion of patients with BMI >30 was significantly greater in NC (39.0%) than
      in NwoC (13.8%) or than in the control group (13.0%). A negative correlation of
      BMI and sleep latency in MSLT (p=0.009) was found in the combined NC and NwoC
      groups. CONCLUSION: Unlike NC, NwoC has neither a higher BMI nor a higher
      incidence of obesity than the general population.

PMID- 21173747
TI  - Influence of metals on cytokines production in connection with successful
      implantation therapy in dentistry.
AB  - OBJECTIVES: In most of patients in need of implantation treatment in the oral
      cavity, implants heal well, nevertheless, there are some individuals, in whom
      titanium implants fail for reasons, which remain unclear. DESIGN: The aim of our
      study was to determine if there is a difference between metal influenced IL
      1beta, IL-4, IL-6, TNF-alpha and IFN-gamma cytokines production in patients with
      successfully healed implants compared to those, whose implant therapy was
      unsuccessful. SETTING: The two study groups included 12 patients with failed
      dental titanium implants and 9 patients with successfully healed implants. In the
      subjects, cytokine production was established after lymphocyte cultivation with
      mercury, nickel and titanium antigens. RESULTS: IL-1beta levels were
      significantly increased in all patients after stimulation with titanium and in
      patients with accepted implants compared to patients with failed implants after
      the stimulation with mercury and titanium. Titanium caused significantly
      increased IL-6 production in all patients. TNF-alpha and IFN-gamma levels were
      also significantly increased after the stimulation with titanium. Significantly
      increased TNF-alpha levels were found in patients with accepted implants as
      compared to patients with failed implants. CONCLUSIONS: Increased production of
      IL-1beta a IL-6 cytokines in reaction to titanium and increased production of TNF
      alpha and IFN-gamma cytokines in reaction to mercury, which is very often present
      in the form of amalgam in the oral cavity of persons in need of implant therapy,
      can play an important role in immune reactions during implant healing process. In
      patients with failed titanium implants, decreased production of these cytokines
      may participate in implant failure.

PMID- 21173746
TI  - Modulation of natural killer cell function by alpha-adrenoreceptor-coupled
      signalling.
AB  - OBJECTIVE: Our previous work has shown that alpha-adrenoreceptor (alpha-AR)
      coupled signaling modulates T lymphocyte function. Here, we investigate the
      expression of alpha1- and alpha2-ARs in natural killer (NK) cells and roles of
      the two subtypes of alpha-ARs and their coupled signals in modulation of NK cell
      function. METHODS: NK cells were purified by Ficoll-Isopaque one-step gradient
      centrifugation and in discontinuous Percoll density gradients from splenic cells
      of rats. The mRNA expressions of alpha1-ARs and alpha2-ARs in NK cells were
      measured by reverse transcription-polymerase chain reaction (RT-PCR). Flow
      cytometry was employed to detect the cytotoxicity of NK cells. RESULTS: NK cells
      expressed both alpha1-AR and alpha2-AR mRNAs. Phenylephrine, a selective alpha1
      AR agonist, increased the cytotoxicity of NK cells. This effect of phenylephrine
      was reduced by corynanthine, a selective alpha1-AR antagonist, and was blocked by
      PLC inhibitor U-73122, but not by PKA inhibitor H-89. Clonidine, a selective
      alpha2-AR agonist, also enhanced the cytotoxicity of NK cells. This action of
      clonidine was blocked by alpha2-AR antagonist yohimbine or by PKA inhibitor H-89,
      but not by PLC inhibitor U-73122. CONCLUSIONS: NK cells express alpha1- and
      alpha2-ARs. Activation of the either subtype of alpha-ARs augments NK cell
      function. This action of alpha1-ARs is transduced by PLC, while alpha2-AR effect
      is mediated by PKA signaling.

PMID- 21173748
TI  - Free leptin index as a marker for leptin action in diabetes and obesity: leptin
      and soluble leptin receptors relationship with HbA1c.
AB  - OBJECTIVES: Glycosylated haemoglobin (HbA1c), leptin, leptin soluble receptors
      (sOB-R) and free leptin index (FLI) may all be influenced by diabetes, but their
      associations remain unclear. Therefore, we put forward a hypothesis that serum
      leptin, sOBR and FLI might be parallel to Hb1c, as they all reflect the metabolic
      status. DESIGN AND SETTING: We measured leptin and sOB-R concentrations in 97
      obese non-diabetic (47 women and 50 men), and 65 obese diabetic (32 women and 33
      men) humans, and examined whether they were related to HbA1c. Under the
      condition, the presence of diabetes was the only differentiating factor between
      two groups of frankly obese humans. RESULTS: Non-diabetic vs. diabetic, median
      and interquartile range, respectively: Leptin (ng/ml), 30.83, 37.27 vs. 28.24,
      23.34; p>0.05; sOB-R (ng/ml), 17.62, 17.05 vs. 21.81, 16.61, p<0.05; FLI, 231.23,
      310.00 vs. 131.76, 157.68, p<0.05. To investigate the influence of HbA1c on
      leptin and sOB-R, both groups were divided into tertiles based on HbA1c. In
      diabetics, leptin did not differ between the high, intermediate, and low HbA1c
      levels subgroups, p>0.05, and leptin was not influenced by HbA1c levels: r=0.086;
      p>0.05. For sOB-R, respectively: p>0.05; r=0.080; p>0.05. In non-diabetics,
      respectively: p<0.05; r=0.2923; p<0.05 for leptin; and p<0.0001, r=0.5103;
      p<0.0001, for s-OB-R. CONCLUSIONS: Not leptin alone but serum sOB-R and FLI are
      the markers of leptin action impairment in type 2 diabetes. Further, HbA1c is not
      associated with metabolic status of leptin in obese diabetic patients, whereas
      this association is found in obese non-diabetic humans.

PMID- 21173749
TI  - Expression and distribution of P450-aromatase in the ovine hypothalamus at
      different stages of fetal development.
AB  - OBJECTIVES: An important step of sexual differentiation is the conversion of
      testosterone to estrogen by aromatase leading to masculinization and
      defeminization of the fetal brain areas crucial for normal sexual behavior and
      reproduction. Brain sexual differentiation occurs throughout a critical period
      starting from different prenatal stages depending on the species. Such period
      goes on from gestation day (GD) 30 to 100GD in the sheep. The fetal sheep brain
      is reported to aromatize androgens to estrogens at 64GD. The main goal of this
      work was to evaluate aromatase expression in sheep hypothalami during the whole
      period of sexual differentiation (35GD, 55GD, 80GD, 115GD) and whether
      differences may be observed depending on gestational stage and sex. METHODS:
      Sections at the hypothalamic level underwent immunoperoxidase technique employing
      anti-aromatase and anti-androgen receptor antibodies. Samples from 35GD and 55GD
      were also processed with in situ hybridization using aromatase cDNA probe. Blot
      analyses were performed to quantify possible aromatase immunoexpression
      differences between sexes. For sexing, samples at 35GD and 55GD underwent DNA
      extraction and SRY amplification. RESULTS: Our results revealed aromatase and
      androgen receptor immunoreactivity along the whole period of sexual
      differentiation. Both molecules were detected in many brain regions and markedly
      in the periventricular area. The highest aromatase and androgen receptor amounts
      were observed at 35GD and 55GD, when aromatase was more abundant in females than
      in males. CONCLUSIONS: In conclusion, the sheep can be included among the species
      where aromatase is highly expressed in the hypothalamus during the whole period
      of sexual differentiation.

PMID- 21173750
TI  - EM66-containing neurones in the hypothalamic parvicellular paraventricular
      nucleus of the rat: no plasticity related to acute immune stress.
AB  - OBJECTIVES AND METHODS: Neuropeptides, as the main neuroendocrine system
      effectors, regulate notably the response to different stressors via a secretory
      plasticity within their respective hypothalamic neuronal populations. The aim of
      the present study was to explore by immunocytochemistry the occurrence and the
      potential expression plasticity of the novel neuropeptide EM66 in the CRH
      neurones of stressed rats. RESULTS: The secretogranin II (SgII)-derived peptide
      EM66 is strongly expressed within hypothalamic neuroendocrine areas such as the
      parvocellular aspect of the paraventricular nucleus (pPVN) as well as the median
      eminence, suggesting a probable hypophysiotropic effect of this peptide. As a
      first approach to investigate such a role, we evaluated by immunohistochemistry
      EM66 expression within the pPVN following acute immune stress induced by
      lipopolysaccharide (LPS) or interleukin-1beta (IL-1beta) injection in rat. This
      study showed that EM66 is present in the pPVN but the number of EM66
      immunolabeled cells did not fluctuate in this structure following LPS peripheral
      injection. In line with this observation, an intracerebroventricular injection of
      IL-1beta did not provoke any significant variation of the number of
      intraparaventricular EM66 neurones. CONCLUSION: The present data revealed for the
      first time that EM66 expression would be insensitive to the central and
      peripheral cytokines within the neurosecretory hypothalamic pPVN. This result
      indicates that EM66 does not participate to the phenotypic plasticity of
      hypothalamic parvicellular neurones in response to acute inflammatory stress.

PMID- 21173751
TI  - Difficulties in diagnosis and treatment of acromegaly in a patient with a McCune
      Albright syndrome. A case report and a review of literature.
AB  - We describe a female patient aged 43, who at the age of five was diagnosed with
      polyostotic fibrous dysplasia (FD). The patient was intermittently treated in our
      department since the age 33, for approximately 10 years, with intravenous
      bisphosphonates. At the age of 42 acromegaly was diagnosed incidentally, since
      clinical manifestations were poor, and, if present earlier, they had been related
      to FD. Only retrospectively, having biochemical confirmation of GH excess, we
      could relate them to acromegaly. Because of the involvement of the base of the
      skull there was no possibility of transphenoidal surgery. Long-acting
      somatostatin analogues were started, but no response was observed, with IGF-1 and
      GH being even higher during than before treatment. After the 37-year-history of
      FD, the occurrence of additional endocrine disorder enabled to make diagnosis of
      McCune-Albright syndrome (MAS) even in the absence of two out of three classical
      manifestations such as cafe-au-lait skin pigmentation and peripheral precocious
      puberty in the past medical history.

PMID- 21173752
TI  - Axelrod, the pineal and the melatonin hypothesis: lessons of 50 years to shape
      chronodisruption research.
AB  - With key work in the 1950s and 1960s, the 1970 Nobel laureate Julius Axelrod made
      major contributions to the development of pineal science. Looking back at some of
      his accomplishments in and for the field, we feel that lessons can be derived for
      future work regarding impairments of the pineal gland's and melatonin's many
      functions for promoting health and preventing disease in man.

PMID- 21173753
TI  - A patient with essential hypernatremia had good response to desmopressin acetate
      therapy.
AB  - OBJECTIVES: Essential hypernatremia is very rare in clinical practice and the
      pathogenesis is unclear. We performed a set of clinical tests to a patient with
      chronic and sustained hypernatremia as well as absence of thirst in order to
      investigate the clinical characteristics and make the diagnosis, yet most
      importantly to analyze the possible pathogenesis and explore a possible therapy
      regime. METHODS: Water deprivation test and acute water intravenous loading test
      were performed to observe the changes of urinary osmolality, plasma osmolality
      and plasma sodium. Free water clearance (C(H2O) was calculated. Osmolality was
      detected using the method of freezing point depression, and thirst grade using
      visual analogue scales. Desmopressin acetate (0.05-0.1 mg/d) was administered to
      the patient in order to observe the therapeutic effects to his disorder. RESULTS:
      The patient had sustained hypernatremia over a long period of time, decreased
      thirst, normal renal function, as well as absence of clinical hypovoluemia. The
      plasma sodium was 160-190 mmol/L and plasma osmolality was 330-370 mOsm/L without
      any thirst perception which could not be corrected by water intake. An 18-hour
      period of water deprivation increased the urinary osmolality from 368 mOsm/L to
      420 mOsm/L with plasma osmolality increasing from 362 mOsm/L to 369 mOsm/L and
      rising further to 857 mOsm/L after an injection of 5 u vasopresin. With the
      infusion of 1 250 ml 5%-glucose during 2 hours in an acute water loading test
      setting, plasma osmolality decreased from 350 mOsm/L to 334 mOsm/L associated
      with a plasma sodium decrease from 164.7 mmol/L to 155 mmol/L urinary osmolality
      dropped from a maximum of 632 mOsm/L to 135 mOsm/L urinary volume from 0.25
      ml/min to 2.33 ml/min and C(H2O) from -0.18 ml/min to 1.19 ml/min after acute
      water loading with 1 250 ml glucose dissolved in water. Our results reveal that
      treatment of the patient with Desmopressin acetate relieved the adypsia,
      hypernatremia and hyperosmolality effectively. CONCLUSIONS: The patient was
      considered as suffering from essential hypernatremia which was associated with
      partial central diabetes insipidus and adypsia. Desmopressin acetate as a common
      therapeutic agent of central diabetes insipidus proved to be an effective
      treatment for essential hypernatremia.

PMID- 21173754
TI  - Vasculitis: Rituximab: effective in ANCA-associated vasculitis?

PMID- 21173762
TI  - Ovarian transplant for transgenic rescue.

PMID- 21173764
TI  - From 'Designated Member' back to 'Full Committee'?

PMID- 21173765
TI  - From 'Designated Member' back to 'Full Committee'? Not too late for FCR.

PMID- 21173766
TI  - From 'Designated Member' back to 'Full Committee'? Sean dropped the ball.

PMID- 21173767
TI  - From 'Designated Member' back to 'Full Committee'? A word from OLAW and USDA.

PMID- 21173768
TI  - From 'Designated Member' back to 'Full Committee'? Talk to the veterinarian!

PMID- 21173769
TI  - Progressive abdominal enlargement and limb weakness in aged, hormonally treated
      female rats.

PMID- 21173771
TI  - Urethral catheterization of the male ferret for treatment of urinary tract
      obstruction.
AB  - Male ferrets are used in various biomedical research studies and generally thrive
      in laboratory conditions. Urethral obstruction can occur in male ferrets of all
      ages, and urethral catheterization may be needed to relieve the obstruction. This
      column describes urinary catheter selection, placement and monitoring in the male
      ferret.

PMID- 21173772
TI  - The role of organizational culture in compliance with the principles of the 3Rs.
AB  - In order for their research to be legitimate, scientists carrying out research
      using animals must comply with rules and regulations. The 3Rs (replacement,
      reduction and refinement) are one set of guidelines that help to promote the
      ethical use of animals for research. An important question is whether
      implementing the principles of the 3Rs in legal regulations, such as a Directive
      of the European Parliament and of the Council on the protection of animals used
      for scientific purposes, will increase compliance with the principles of the 3Rs
      in research organizations. Previous work suggests that organizational culture is
      just as important for directing behavior as are formalized rules and regulations.
      This article introduces the concepts of compliance and organizational culture and
      discusses their consequences on the implementation of the principles of the 3Rs.

PMID- 21173773
TI  - Development: Hourglass theory gets molecular approval.

PMID- 21173774
TI  - Human Disease: Next-generation sequencing of the next generation.

PMID- 21173775
TI  - Elucidating the inosinome: global approaches to adenosine-to-inosine RNA editing.
AB  - Catalysed by members of the adenosine deaminase acting on RNA (ADAR) family of
      enzymes, adenosine-to-inosine (A-to-I) editing converts adenosines in RNA
      molecules to inosines, which are functionally equivalent to guanosines. Recently,
      global approaches to studying this widely conserved phenomenon have emerged. The
      use of bioinformatics, high-throughput sequencing and other approaches has
      increased the number of known editing sites by several orders of magnitude, and
      we now have a greater understanding of the control and the biological
      significance of editing. This Progress article reviews some of these recent
      global studies and their results.

PMID- 21173777
TI  - Superimposed myasthenia gravis in chronic spinal cord injury: a case report.
AB  - STUDY DESIGN: Case report. BACKGROUND/OBJECTIVE: Myasthenia gravis (MG)
      complicating spinal cord injury (SCI) is extremely rare. We report a patient with
      SCI developing MG leading to death. There are no similar articles at present on
      literature search. CASE REPORT: A 54-year-old man, paralysed at the T12 level
      (ASIA A) for 40 years, was admitted for surgical repair of his grade IV sacral
      pressure sore. During the admission he developed diplopia, fluctuating dysphagia
      and slurred speech. Elevated anti-acetylcholine receptor antibodies and single
      fibre electromyography confirmed the diagnosis of MG and pyridostigmine was
      commenced. His admission was complicated by intermittent episodes of unexplained
      tachycardia and tachypnoea. He succumbed following cardio respiratory within 6
      weeks of admission. Post mortem examination was inconclusive of a definite cause
      of death. In the presence of SCI, it can be challenging to diagnose MG or its
      complications like myasthenic and cholinergic crisis. CONCLUSION: The case
      highlights the difficulty in diagnosis and management of MG in persons with SCI.

PMID- 21173778
TI  - Thoracolumbar multisegmental motor responses in the upper and lower limbs in
      healthy subjects.
AB  - STUDY DESIGN: Experimental design. OBJECTIVES: This descriptive study presents
      muscular responses from both the upper and the lower extremities during T11-12
      segmental stimulation. SETTING: Neuro Lab of the Texas Woman's University (School
      of Physical Therapy, TX, USA). METHODS: A total of 13 healthy subjects were
      electrically stimulated using surface electrodes. In trial 1, signals were
      recorded from the flexor hallucis brevis, soleus, vastus medialis and gluteus
      medius in the lower right extremity. In trial 2, responses were recorded from the
      abductor digiti minimi, abductor pollicis brevis (APB), flexor carpi radialis and
      biceps brachii in the right upper extremity. In trial 3, stimulation was carried
      out and signals were recorded for both the upper and the lower extremities
      simultaneously, using different muscle combinations. Five traces per muscle were
      averaged for each step of the testing. Amplitude and deflection latency were the
      measured parameters and were compared using descriptive statistics. RESULTS:
      Results showed signal amplitudes ranging from 85 to 821 MUV in the upper
      extremity and from 582 to 3927 MUV in the lower extremity, with the largest
      signal recorded in the soleus muscle and the APB. Response latency varies between
      5.5 and 14 ms in the upper limbs and between 7.7 and 27 ms in the lower limbs and
      was comparable in bilateral recording. CONCLUSION: These muscular responses seem
      to be elicited from electrical stimulation of motor nuclei in lower limb muscles
      or from pathways to those nuclei in upper limb muscles, and could be useful in
      testing patients with spinal disorders.

PMID- 21173779
TI  - Case report by RN Mohapatra: urine leakage in persons with spinal cord injury and
      using long-term Foley catheters: a simple solution.

PMID- 21173776
TI  - Meta-analysis of genome-wide association studies for personality.
AB  - Personality can be thought of as a set of characteristics that influence people's
      thoughts, feelings and behavior across a variety of settings. Variation in
      personality is predictive of many outcomes in life, including mental health. Here
      we report on a meta-analysis of genome-wide association (GWA) data for
      personality in 10 discovery samples (17,375 adults) and five in silico
      replication samples (3294 adults). All participants were of European ancestry.
      Personality scores for Neuroticism, Extraversion, Openness to Experience,
      Agreeableness and Conscientiousness were based on the NEO Five-Factor Inventory.
      Genotype data of ~ 2.4M single-nucleotide polymorphisms (SNPs; directly typed and
      imputed using HapMap data) were available. In the discovery samples, classical
      association analyses were performed under an additive model followed by meta
      analysis using the weighted inverse variance method. Results showed genome-wide
      significance for Openness to Experience near the RASA1 gene on 5q14.3 (rs1477268
      and rs2032794, P=2.8 * 10(-8) and 3.1 * 10(-8)) and for Conscientiousness in the
      brain-expressed KATNAL2 gene on 18q21.1 (rs2576037, P=4.9 * 10(-8)). We further
      conducted a gene-based test that confirmed the association of KATNAL2 to
      Conscientiousness. In silico replication did not, however, show significant
      associations of the top SNPs with Openness and Conscientiousness, although the
      direction of effect of the KATNAL2 SNP on Conscientiousness was consistent in all
      replication samples. Larger scale GWA studies and alternative approaches are
      required for confirmation of KATNAL2 as a novel gene affecting Conscientiousness.

PMID- 21173780
TI  - Reliability of non-invasive cardiac output measurement in individuals with
      tetraplegia.
AB  - STUDY DESIGN: The study is conducted on the basis of comparative-repeated
      measures. OBJECTIVES: The objective of this study is to assess the reliability of
      non-invasive cardiac output (CO) measurements in individuals with tetraplegia
      (TP) at rest and during exercise using Innocor, and to test the hypothesis that
      CO measurements are less reliable in TP than in able-bodied (AB) individuals.
      SETTING: Ambulatory volunteers, Switzerland. METHODS: Nine male motor-complete TP
      (C5-C7) and nine pair-matched AB performed repeated CO measurements at rest and
      during submaximal arm-crank and wheelchair exercises in four different test
      sessions. Within- and between-day reliabilities were compared between TP and AB.
      RESULTS: Mean differences between measurements at rest (TP vs AB, within-day:
      0.1+/-0.5 vs 0.2+/-0.6 l min(-1), between-day: -0.7+/-0.6 vs -0.1+/-0.8 l min(
      1)), during arm-crank (TP vs AB, within-day: 0.1+/-0.9 vs 0.5+/-0.7 l min(-1),
      between-day: -0.3+/-1.1 vs 0.0+/-1.1 l min(-1)) and wheelchair exercises (TP vs
      AB, within-day: 0.3+/-1.2 vs -0.1+/-0.8 l min(-1), between-day: 0.1+/-1.1 vs
      0.5+/-0.9 l min(-1)) were not significantly different between TP and AB (all
      P>0.05). Coefficients of variation in TP (within-day, rest: 6.8%, arm-crank: 9.6%
      and wheelchair: 10.8%; between-day, rest: 11.9%, arm-crank: 11.2% and wheelchair:
      10.3%) and in AB (within-day, rest: 7.7%, arm crank: 6.8% and wheelchair: 6.0%;
      between-day, rest: 9.2%, arm crank: 8.5% and wheelchair: 8.0%) indicated
      acceptable reliability. CONCLUSION: In contrast to our hypothesis, we found non
      invasive CO measurements using Innocor to be as reliable in TP as they are in AB.
      Consequently, Innocor can be recommended for repeated assessments of CO in TP
      within routine diagnostics or for evaluation of training progress.

PMID- 21173781
TI  - Cardiovascular control during head-up tilt test in spinal cord injury patients.

PMID- 21173782
TI  - Evaluating vaccinia virus cytokine co-expression in TLR GKO mice.
AB  - Using Toll-like receptor (TLR) and MyD88 gene knock-out (GKO) mice the effect of
      TLRs and MyD88 on virus replication, interferon (IFN)-beta production, natural
      killer (NK) cell and CD8T cell responses were assessed following ectromelia virus
      (ECTV) and recombinant vaccinia virus (rVV) infection. The capacity for rVVs
      encoding cytokines to restore immune function in MyD88(-/-) mice was clearly
      demonstrated. Results showed that TLR2(-/-), TLR4(-/-)and TLR7(-/-) mice survived
      ECTV infection whereas MyD88(-/-) and TLR9(-/-)mice, in contrast, were highly
      susceptible. Next, following infection with rVV, MyD88(-/-) mice elicited reduced
      serum IFN-beta, NK cell and CD8T cell responses compared with wild-type mice,
      whereas TLR9(-/-) mice showed elevated CD8T cell responses. When MyD88(-/-)mice
      were infected with rVV co-expressing IFN-beta these mice were able to restore IFN
      beta levels and CD8T cell responses but not NK cell activation. Interestingly,
      even though rVV co-expressing interleukin (IL)-2 enhanced NK cell activation in
      MyD88(-/-) mice, this was not associated with an antiviral effect, as observed in
      normal mice. Surprisingly, co-infection with rVV IL-2/rVV IL-12, but not rVV IL
      2/rVV IFN-beta, restored the attenuated phenotype of rVV IL-2 in MyD88(-/-) mice
      indicating that the IL-2/IL-12 combination promotes antiviral responses. Our
      results clearly show that the CD8T cell defect observed in MyD88(-/-) mice to
      vaccinia virus infection can be restored by rVV-encoding IFN-beta demonstrating
      the critical role of this cytokine in T cell mediated immunity and illustrates
      that the model can provide an effective platform for the elucidation of cytokine
      immunobiology.

PMID- 21173783
TI  - Antibody memory: a question of life or death beyond the germinal center.

PMID- 21173784
TI  - Versatility in NK cell memory.

PMID- 21173785
TI  - Global pharmacogenomics: Impact of population diversity on the distribution of
      polymorphisms in the CYP2C cluster among Brazilians.
AB  - The impact of biogeographical ancestry, self-reported 'race/color' and
      geographical origin on the frequency distribution of 10 CYP2C functional
      polymorphisms (CYP2C8*2, *3, *4, CYP2C9*2, *3, *5, *11, CYP2C19*2, *3 and *17)
      and their haplotypes was assessed in a representative cohort of the Brazilian
      population (n=1034). TaqMan assays were used for allele discrimination at each
      CYP2C locus investigated. Individual proportions of European, African and
      Amerindian biogeographical ancestry were estimated using a panel of insertion
      deletion polymorphisms. Multinomial log-linear models were applied to infer the
      statistical association between the CYP2C alleles and haplotypes (response
      variables), and biogeographical ancestry, self-reported Color and geographical
      origin (explanatory variables). The results showed that CYP2C19*3, CYP2C9*5 and
      CYP2C9*11 were rare alleles (<1%), the frequency of other variants ranged from
      3.4% (CYP2C8*4) to 17.3% (CYP2C19*17). Two distinct haplotype blocks were
      identified: block 1 consists of three single nucleotide polymorphisms (SNPs)
      (CYP2C19*17, CYP2C19*2 and CYP2C9*2) and block 2 of six SNPs (CYP2C9*11,
      CYP2C9*3, CYP2C9*5, CYP2C8*2, CYP2C8*4 and CYP2C8*3). Diplotype analysis
      generated 41 haplotypes, of which eight had frequencies greater than 1% and
      together accounted for 96.4% of the overall genetic diversity. The distribution
      of CYP2C8 and CYP2C9 (but not CYP2C19) alleles, and of CYP2C haplotypes was
      significantly associated with self-reported Color and with the individual
      proportions of European and African genetic ancestry, irrespective of Color self
      identification. The individual odds of having alleles CYP2C8*2, CYP2C8*3,
      CYP2C9*2 and CYP2C9*3, and haplotypes including these alleles, varied
      continuously as the proportion of European ancestry increased. Collectively,
      these data strongly suggest that the intrinsic heterogeneity of the Brazilian
      population must be acknowledged in the design and interpretation of
      pharmacogenomic studies of the CYP2C cluster in order to avoid spurious
      conclusions based on improper matching of study cohorts. This conclusion extends
      to other polymorphic pharmacogenes among Brazilians, and most likely to other
      admixed populations of the Americas.

PMID- 21173786
TI  - Intuitive pharmacogenetics: spontaneous risperidone dosage is related to CYP2D6,
      CYP3A5 and ABCB1 genotypes.
AB  - The aim of this study is to evaluate whether the quantitative prescription of
      risperidone (dosage) is related to the patient's metabolic status. Metabolic
      status was defined in terms of the most relevant polymorphisms of CYP2D6 (*3, *4,
      *5, *6 and *1xN), CYP3A5 (*3A) and ABCB1 (G2677T) determined a posteriori and
      blinded to the clinicians. This prospective and observational study includes a
      cohort of 151 Caucasian psychiatric patients treated with risperidone.
      Significant differences (Kruskal-Wallis test p=0.01) among the doses administered
      were observed to correlate (Spearman's r=1, p=0.02) with the different CYP2D6
      groups. Poor metabolizers received the lowest doses and ultra rapid metabolizers
      the highest. No significant correlations were observed with regard to CYP3A5 and
      ABCB1. We find that, despite not knowing patients' metabolic status, clinicians
      modify risperidone dosage in order to obtain the best therapeutic option.

PMID- 21173787
TI  - Three-gene predictor of clinical outcome for gastric cancer patients treated with
      chemotherapy.
AB  - To identify transcriptional profiles predictive of the clinical benefit of
      cisplatin and fluorouracil (CF) chemotherapy to gastric cancer patients,
      endoscopic biopsy samples from 96 CF-treated metastatic gastric cancer patients
      were prospectively collected before therapy and analyzed using high-throughput
      transcriptional profiling and array comparative genomic hybridization.
      Transcriptional profiling identified 917 genes that are correlated with poor
      patient survival after CF at P<0.05 (poor prognosis signature), in which protein
      synthesis and DNA replication/recombination/repair functional categories are
      enriched. A survival risk predictor was then constructed using genes, which are
      included in the poor prognosis signature and are contained within identified
      genomic amplicons. The combined expression of three genes-MYC, EGFR and FGFR2-was
      an independent predictor for overall survival of 27 CF-treated patients in the
      validation set (adjusted P=0.017), and also for survival of 40 chemotherapy
      treated gastric cancer patients in a published data set (adjusted P=0.026). Thus,
      combined expression of MYC, EGFR and FGFR2 is predictive of poor survival in CF
      treated metastatic gastric cancer patients.

PMID- 21173788
TI  - Pharmacogenetic analysis of the mGlu2/3 agonist LY2140023 monohydrate in the
      treatment of schizophrenia.
AB  - The goal of this study was to identify genetic markers associated with LY2140023
      monohydrate response in patients with schizophrenia. Variants in eight candidate
      genes related to the mechanism of action of LY2140023 or olanzapine were
      investigated in a genetic cohort collected from two clinical trials. Results from
      this genetic analysis indicate that 23 single nucleotide polymorphisms (SNPs)
      were associated with a change in Positive and Negative Syndrome Scale total score
      in response to LY2140023 at 28 days (P<0.01; false discovery rate <0.2). Sixteen
      of these SNPs were located in the serotonin 2A receptor (HTR2A). Bioinformatic
      analyses identified a putative antisense nested gene in intron 2 of HTR2A in the
      region of the genetic markers associated with LY2140023 response. These data
      suggest a genetic association exists between SNPs in several genes, such as
      HTR2A, and response to LY2140023 treatment. Additional clinical trials are needed
      to establish replication of these results.

PMID- 21173790
TI  - Chronic kidney disease: blood-pressure targets in chronic kidney disease.

PMID- 21173791
TI  - Prognostic value of connexin43 expression in patients with clinically localized
      prostate cancer.
AB  - Connexins (Cxs) are a family of transmembrane proteins that build cell-to-cell
      channels in gap junctions. Gap junctions composed of Cxs have an essential role
      in intercellular communication, adhesion and cell differentiation. Several
      studies investigated the role of connexin43 (Cx43) in different carcinomas;
      however, none investigated its prognostic role in prostate cancer. Cx43
      expression and relationship with established prognostic features were assessed in
      a cohort of 102 patients treated with radical prostatectomy for clinically
      localized prostate adenocarcinoma. Cx43 expression in prostate cancer was
      significantly associated with established features indicative of worse prognosis,
      such as follow-up time (P < 0.001) and preoperative PSA (P < 0.007). Patients
      with lower Cx43 expressions in tumours have shorter follow-up time, which
      indicated shorter disease-free survival and higher preoperative PSA values.
      Furthermore, tumours with positive surgical margins (P < 0.001) showed
      significantly lower Cx43 expression compared with tumours without this feature.
      In univariate (P < 0.001) and multivariate (P = 0.014) analyses, decreased Cx43
      expression was found to be a significant predictor of biochemical recurrence free
      survival. Study results show the association of decreased Cx43 expression with
      prostate cancer progression. Moreover, Cx43 could serve as an additional
      prognostic marker and used together with traditional prognostic markers might
      help in further stratifying the risk of disease progression in patients with
      prostate cancer.

PMID- 21173792
TI  - The benefits of timely intervention with zoledronic acid in patients with
      metastatic prostate cancer to bones: a retrospective study of the US Veterans
      Affairs population.
AB  - To examine the effect of timely zoledronic acid (ZA) treatment on clinical
      outcomes and health care utilization in patients with bone-metastatic prostate
      cancer. Patients with prostate cancer and bone metastasis were identified in a
      Veterans Affairs database (01/2002-09/2009). Eligible patients had no documented
      skeletal-related events (SREs) before the index date (that is, the first bone
      metastasis diagnosis date). Patients who received early ZA treatment, defined as
      having a ZA infusion after the index date and before any recorded SREs, were
      matched 1:1 on propensity score to patients not treated with bisphosphonates
      (BPs). Risks of SREs, hospitalization and death during the 6-month post-index
      period were compared between matched cohorts using Kaplan-Meier analyses.
      Baseline characteristics were well balanced between the matched cohorts (n = 73
      per group). 6-month SRE-free survival and hospitalization-free survival were
      higher in patients receiving timely ZA than patients without BP treatment (91.7
      versus 71.5%, P < 0.01; 80.5 versus 66.3%, P = 0.05, respectively). 6-month
      mortality risk was significantly lower in patients treated with ZA versus those
      without BP treatment (4.3 versus 13.8%, P = 0.04). Timely ZA intervention in bone
      metastatic prostate cancer patients was associated with significant reductions in
      6-month risks of SREs, hospitalization and mortality, as compared with no BP
      treatment.

PMID- 21173789
TI  - Treatment of proliferative lupus nephritis: a slowly changing landscape.
AB  - Proliferative lupus nephritis is the most severe form of lupus nephritis.
      Outcomes of this disease are affected by ethnicity, clinical characteristics,
      irreversible damage on renal biopsy, initial response to treatment and future
      disease course (for example, the occurrence of renal flares). Initial intensive
      (induction) treatment of proliferative lupus nephritis is aimed at achieving
      remission, but optimal duration and intensity are not well defined. A combination
      of intravenous cyclophosphamide and corticosteroids have been shown to decrease
      the risk of end-stage renal disease, but are associated with substantial acute
      toxic effects (such as infections) and chronic toxic effects (such as ovarian
      failure). In white populations, low-dose cyclophosphamide is a reasonable
      alternative to high-dose cyclophosphamide as it is similarly effective and
      associated with less toxicity. Mycophenolate mofetil is as effective as high-dose
      intravenous cyclophosphamide in terms of inducing remission and similar in terms
      of safety. Although most patients respond to induction treatment, remission is
      often only achieved after patients are switched to maintenance treatment. As
      maintenance treatment, mycophenolate mofetil is superior to azathioprine and
      azathioprine is similarly effective to ciclosporin in terms of prevention or
      reducing the risk of relapse. Rituximab should be reserved for patients with
      refractory disease. Treatment of lupus nephritis should be individually tailored
      to patients, with more aggressive therapy reserved for patients at high risk of
      renal dysfunction and progression of renal disease.

PMID- 21173793
TI  - The evolving epidemiology of acute coronary syndromes.
AB  - The clinical entities that comprise acute coronary syndromes (ACS)-ST-segment
      elevation myocardial infarction (STEMI), non-STEMI, and unstable angina-have been
      recognized as widespread causes of death and disability for more than a century.
      Seminal research in the past 50 years has led to important scientific and medical
      advances in our understanding of ACS. Rapid modernization of the developing world
      has led to a pandemic of coronary artery disease and its manifestation as ACS,
      with profound implications for personal, societal, and global health.
      Epidemiological studies have provided insight into the changing demographics of
      ACS, and highlighted the importance of modifiable risk factors and adherence to
      guideline-recommended therapy.

PMID- 21173794
TI  - Epidemiology of thoracic aortic dissection.
AB  - Thoracic aortic dissection (TAD) is estimated to occur at a rate of 3-4 cases per
      100,000 persons per year and is associated with a high mortality. Reported rates
      are probably underestimates of the true incidence of TAD because of difficulties
      in diagnosis. The incidence of TAD appears to have been increasing over time. TAD
      is most common in men and older individuals. Aortic dilatation is a well
      established risk factor for TAD but is not a prerequisite; most ascending aortic
      dissections occur when aortic diameter is <5.5 cm. Although atherosclerosis and
      typical cardiovascular risk factors, such as hypertension and smoking, are
      associated with TAD, evidence supporting their direct causal role is lacking.
      Notably, diabetes mellitus is remarkably uncommon in patients with TAD. Other
      risk factors for TAD include inflammatory diseases, iatrogenic aortic injury, and
      drug use. Congenital cardiovascular defects, such as bicuspid aortic valve, and
      certain genetic syndromes, such as Marfan syndrome, are the genetic factors most
      commonly associated with TAD. Specific nonsyndromic genetic mutations in families
      and single nucleotide polymorphisms have also been identified as possible risk
      factors for TAD.

PMID- 21173795
TI  - A case revealing the natural history of untreated Lyme disease.
AB  - BACKGROUND: A 71-year-old woman presented to a rheumatologist with what she
      believed to be a 2-year history of Lyme disease, progressing from erythema
      migrans to Lyme arthritis. INVESTIGATIONS: History, physical examination and
      serologic testing confirmed the diagnosis of Lyme disease. DIAGNOSIS: Lyme
      disease. MANAGEMENT: The patient refused antibiotic therapy during the first 2
      years of her illness. During the next 2 years, she consulted a rheumatologist,
      but declined antibiotic therapy. She continued to have recurrent episodes of
      arthritis, following which she was successfully treated with doxycycline, given
      initially for 2 weeks, with a second, 4-week cycle administered 2 months later.
      This case illustrates the natural history of untreated Lyme disease, which is
      rarely observed in most patients since diagnosis almost always leads to
      successful antibiotic treatment. Furthermore, this case also demonstrates that
      infection with Borrelia burgdorferi can persist for years in untreated patients;
      however, antibiotic therapy is still likely to be effective, despite long-term
      infection.

PMID- 21173796
TI  - Non-canonical NF-kappaB signaling pathway.
AB  - The non-canonical NF-kappaB pathway is an important arm of NF-kappaB signaling
      that predominantly targets activation of the p52/RelB NF-kappaB complex. This
      pathway depends on the inducible processing of p100, a molecule functioning as
      both the precursor of p52 and a RelB-specific inhibitor. A central signaling
      component of the non-canonical pathway is NF-kappaB-inducing kinase (NIK), which
      integrates signals from a subset of TNF receptor family members and activates a
      downstream kinase, IkappaB kinase-alpha (IKKalpha), for triggering p100
      phosphorylation and processing. A unique mechanism of NIK regulation is through
      its fate control: the basal level of NIK is kept low by a TRAF-cIAP destruction
      complex and signal-induced non-canonical NF-kappaB signaling involves NIK
      stabilization. Tight control of the fate of NIK is important, since deregulated
      NIK accumulation is associated with lymphoid malignancies.

PMID- 21173798
TI  - Combating scientific misconduct.
AB  - The pressures of an increasingly competitive research environment can lead to
      scientific misconduct. Journals, academic institutions and individual scientists
      should commit to promoting best practice in research and education in research
      ethics.

PMID- 21173799
TI  - Out of Africa and into epigenetics: discovering reprogramming drugs.

PMID- 21173797
TI  - Malaria parasites form filamentous cell-to-cell connections during reproduction
      in the mosquito midgut.
AB  - Physical contact is important for the interaction between animal cells, but it
      can represent a major challenge for protists like malaria parasites. Recently,
      novel filamentous cell-cell contacts have been identified in different types of
      eukaryotic cells and termed nanotubes due to their morphological appearance.
      Nanotubes represent small dynamic membranous extensions that consist of F-actin
      and are considered an ancient feature evolved by eukaryotic cells to establish
      contact for communication. We here describe similar tubular structures in the
      malaria pathogen Plasmodium falciparum, which emerge from the surfaces of the
      forming gametes upon gametocyte activation in the mosquito midgut. The filaments
      can exhibit a length of > 100 MUm and contain the F-actin isoform actin 2. They
      actively form within a few minutes after gametocyte activation and persist until
      the zygote transforms into the ookinete. The filaments originate from the
      parasite plasma membrane, are close ended and express adhesion proteins on their
      surfaces that are typically found in gametes, like Pfs230, Pfs48/45 or Pfs25, but
      not the zygote surface protein Pfs28. We show that these tubular structures
      represent long-distance cell-to-cell connections between sexual stage parasites
      and demonstrate that they meet the characteristics of nanotubes. We propose that
      malaria parasites utilize these adhesive "nanotubes" in order to facilitate
      intercellular contact between gametes during reproduction in the mosquito midgut.

PMID- 21173800
TI  - Reducing background fluorescence reveals adhesions in 3D matrices.

PMID- 21173804
TI  - Histone acetylation influences the activity of Sox9-related transcriptional
      complex.
AB  - Chondrocyte differentiation is the fundamental process in skeletal development.
      From the mesenchymal condensation of chondroprogenitors to the hypertrophic
      maturation of chondrocytes, chondrogenesis is sequentially regulated by cross
      talk among transcription factors, growth factors, and chromatin structure. The
      master transcription factor Sry-type HMG box (Sox) 9 has an essential role in the
      expression of chondrogenic genes through the association with Sox9-binding sites
      on its target genes. Several transcription factors and coactivators, such as
      Scleraxis/E47 and p300, cooperatively modulate the Sox9-dependent transcription
      by interacting with Sox9. The Sox9-related transcriptional apparatus activates
      its target gene expression through p300-mediated histone acetylation on
      chromatin. The transforming growth factor (TGF)-beta superfamily also plays a key
      role in chondrocyte differentiation. The TGF-beta-regulated Smad3/4 complex
      activates Sox9-dependent transcription on chromatin by associating with Sox9
      itself, and by recruiting p300 onto Sox9. These findings suggest that the
      epigenetic status including histone modification and chromatin structure,
      directly influences Sox9-regulated chondrocyte differentiation. In this article,
      we review the regulators of Sox9 expression itself, modulators of
      posttranslational Sox9 function, and Sox9-associating factors in the Sox9
      dependent epigenetic regulation during chondrogenesis.

PMID- 21173805
TI  - Submucosal electrocoagulation for prolapsed hemorrhoids:a new operative approach
      to hemorrhoidal varices.
AB  - The results of submucosal electrocoagulation (SEC), a new radical operation for
      prolapsed hemorrhoids, in 403 patients with third- or fourth-degree hemorrhoids
      are reported. After resecting the anal skin tags that coexisted with prolapsed
      hemorrhoids, the hemorrhoidal varices could be resected and electrically
      coagulated through the wound without cutting the anal canal epithelium by using a
      fine needle-type electric knife. The results of this series indicated that SEC
      could dramatically reduce the incidence of the postoperative complications that
      sometimes occur after conventional hemorrhoidectomy, such as severe anal pain,
      massive anal bleeding and anal stenosis. Moreover, SEC could ensure that operated
      patients make an early return to social activities and have a satisfactory
      quality of life. Relapse of prolapsed hemorrhoids after SEC was rare.

PMID- 21173802
TI  - Chaperoning the SNAREs: a role in preventing neurodegeneration?
AB  - Despite their potential importance as therapeutic targets, the initial events in
      neurodegenerative diseases are poorly understood. Emerging evidence suggests that
      presynaptic dysfunction might be an early event in these pathologies, and three
      papers now link dysregulation of SNAREprotein levels and function caused by the
      absence of synuclein or cysteine string protein (CSP) to activity-dependent
      neurodegeneration.

PMID- 21173806
TI  - Incidence and mutation analysis of glucose-6-phosphate dehydrogenase deficiency
      in eastern Indonesian populations.
AB  - We conducted a field survey of glucose-6-phosphate dehydrogenese (G6PD)
      deficiency in the eastern Indonesian islands, and analyzed G6PD variants
      molecularly. The incidence of G6PD deficiency in 5 ethnic groups (Manggarai,
      Bajawa, Nage-Keo, Larantuka, and Palue) on the Flores and Palue Islands was lower
      than that of another native group, Sikka, or a nonnative group, Riung. Molecular
      analysis of G6PD variants indicated that 19 cases in Sikka had a frequency
      distribution of G6PD variants similar to those in our previous studies, while 8
      cases in Riung had a different frequency distribution of G6PD variants. On the
      other hand, from field surveys in another 8 ethnic groups (Timorese, Sumbanese,
      Savunese, Kendari, Buton, Muna, Minahasa, and Sangirese) on the islands of West
      Timor, Sumba, Sulawesi, Muna and Bangka, a total of 49 deficient cases were
      detected. Thirty-nine of these 49 cases had G6PD Vanua Lava (383T>C) of
      Melanesian origin. In our previous studies, many cases of G6PD Vanua Lava were
      found on other eastern Indonesian islands. Taken together, these findings may
      indicate that G6PD Vanua Lava is the most common variant in eastern Indonesian
      populations, except for Sikka.

PMID- 21173807
TI  - Comparing the cochlear spiral modiolar artery in type-1 and type-2 diabetes
      mellitus:a human temporal bone study.
AB  - This study examined whether pathological findings were present in cochlear
      vessels for patients with diabetes mellitus. Twenty-six temporal bones from 13
      patients with type 1 diabetes mellitus and 40 temporal bones from 20 patients
      with type 2 diabetes mellitus were examined. Type 2 diabetic temporal bones were
      divided into 2 groups according to diabetic management (22 temporal bones with
      insulin therapy, and 18 with oral hypoglycemic drugs). Age-matched normal control
      temporal bones were also selected. The vessel wall thickness in the cochlear
      spiral modiolar artery was measured under a light microscope, and the vessel wall
      ratio (vessel wall thickness/outer diameter of the vessel x 100) was calculated.
      The vessel wall thickness and vessel wall ratio in type 1 diabetes mellitus were
      significantly greater than in normal controls. Type 2 diabetic patients with
      insulin therapy showed significantly greater vessel wall thickness and vessel
      wall ratios than controls. In type 2 diabetes mellitus, the vessel wall thickness
      and vessel wall ratio were greater in patients treated with insulin therapy than
      in those treated with oral hypoglycemic agents. Type 2 diabetic patients with
      insulin therapy showed an increased vessel wall thickness and vessel wall ratio
      compared to patients with type 1 diabetes mellitus. In conclusion, the cochlea in
      patients with diabetes mellitus shows circulatory disturbance compared to age
      matched normal controls.

PMID- 21173808
TI  - Influence of cigarette smoking on estimated glomerular filtration rate (eGFR) in
      Japanese male workers.
AB  - The link between changes in estimated glomerular filtration rate (eGFR) and
      cigarette smoking was evaluated in Japanese male workers with a 5-year follow-up.
      We examined the data of 456 Japanese male workers, aged 22-70 years, who were
      taking no medications, and from this group, 286 men (43.5+/-8.2 years) were
      followed for 5-years. Habits of cigarette smoking were obtained during interviews
      by well-trained staff. The influence of cigarette smoking on eGFR was evaluated.
      In the first analysis, there was no significant difference in eGFR between
      subjects with and without cigarette smoking. In the second analysis, eGFR was
      significantly reduced after 5 years in all subjects. Changes in eGFR in subjects
      with cigarette smoking (-1.90+/-12.31 ml/min/1.73 m2) were significantly smaller
      than those in subjects without cigarette smoking (-4.97+/-12.05 ml/min/1.73 m2).
      At follow-up, we found that eGFR was weakly and negatively correlated with the
      number of cigarettes smoked (/day). The present study indicated that cigarette
      smoking may be an important modifiable factor for eGFR in Japanese male workers
      who are not taking any medications.

PMID- 21173809
TI  - Evaluation of the appropriate root pressure for maintaining heartbeat during an
      aortic cross-clamp for primary repair of the aortic arch in premature infants
      with associated cardiac anomalies.
AB  - We developed a new cardiopulmonary bypass (CPB) method to minimize myocardial
      damage during aortic arch reconstruction. In this method, coronary flow and
      heartbeat were stabilized by maintaining the aortic root pressure with an
      adjusted preload of the ventricle during aortic cross-clamping. This study was
      performed to determine the appropriate root pressure to maintain the heartbeat
      without causing deterioration of ventricular function. Study 1. Under partial
      CPB, the ascending aorta was cross-clamped in 6 pigs (group 1). Experimental data
      at various systolic aortic root pressures was analysed to determine the
      appropriate root pressure. Study 2. In group 2 (control, n=6), the aorta was not
      clamped, while in group 3 (n=6), the aorta was cross-clamped for 60 min and the
      systolic aortic root pressure was maintained at the pressure determined in study
      1. Study 1. The diastolic coronary flow was stabilized at values comparable to
      that before initiation of CPB (6.6+/-1.4 ml/beat) when the systolic aortic root
      pressure was above 80 mmHg. Intracardiac pressure and the myocardial oxygen
      consumption (MvO2) seemed to be acceptable when the systolic aortic root pressure
      was below 100 mmHg. Therefore, 90 mmHg was selected for study 2. Study 2.
      Perioperative cardiac function did not differ between the groups. We concluded
      that 90 mmHg was the systolic aortic root pressure appropriate for this method.

PMID- 21173810
TI  - Effects of natto extract on endothelial injury in a rat model.
AB  - Vascular endothelial damage has been found to be associated with thrombus
      formation, which is considered to be a risk factor for cardiovascular disease. A
      diet of natto leads to a low prevalence of cardiovascular disease. The aim of the
      present study was to investigate the effects of natto extract on vascular
      endothelia damage with exposure to laser irradiation. Endothelial damage both in
      vitro and in vivo was induced by irradiation of rose bengal using a DPSS green
      laser. Cell viability was determined by MTS assay, and the intimal thickening was
      verified by a histological approach. The antioxidant content of natto extract was
      determined for the free radical scavenging activity. Endothelial cells were
      injured in the presence of rose bengal irradiated in a dose-dependent manner.
      Natto extract exhibits high levels of antioxidant activity compared with purified
      natto kinase. Apoptosis of laser-injured endothelial cells was significantly
      reduced in the presence of natto extract. Both the natto extract and natto kinase
      suppressed intimal thickening in rats with endothelial injury. The present
      findings suggest that natto extract suppresses vessel thickening as a synergic
      effect attributed to its antioxidant and anti-apoptosis properties.

PMID- 21173812
TI  - Multiframe image estimation for coded aperture snapshot spectral imagers.
AB  - A coded aperture snapshot spectral imager (CASSI) estimates the three-dimensional
      spatiospectral data cube from a snapshot two-dimensional coded projection,
      assuming that the scene is spatially and spectrally sparse. For less spectrally
      sparse scenes, we show that the use of multiple nondegenerate snapshots can make
      data cube recovery less ill-posed, yielding improved spatial and spectral
      reconstruction fidelity. Additionally, data acquisition can be easily scaled to
      meet the time/resolution requirements of the scene with little modification or
      extension of the original CASSI hardware. A multiframe reconstruction of a 640 *
      480 * 53 voxel datacube with 450-650 nm white-light illumination of a scene
      reveals substantial improvement in the reconstruction fidelity, with limited
      increase in acquisition and reconstruction time.

PMID- 21173811
TI  - Sarcoidosis-associated hepatocellular carcinoma.
AB  - Sarcoidosis is a systemic granulomatous inflammation of unknown etiology, and
      seems to involve the liver parenchyma in most cases. However, sarcoidosis
      associated hepatocellular carcinoma is rare. We report here a case in which a
      hepatocellular carcinoma occurred within the liver, which was probably involved
      as a result of systemic sarcoidosis. A 57-year-old Japanese man had been followed
      up for 2 years because of diabetic nephropathy and sarcoidosis. On admission for
      pneumonia, imaging studies revealed an unexpected hepatic tumor. Histology
      revealed a hepatocellular carcinoma accompanied by T-lymphocytic infiltration and
      marked granulomatous inflammation, which was surrounding some tumor nodules. The
      background liver parenchyma exhibited a moderate degree of fibrosis with
      granulomatous inflammation. The patient had no other apparent liver disease such
      as viral hepatitis, steatohepatitis, or primary biliary cirrhosis. Therefore, in
      the present case, sarcoidosis may be considered the probable background etiology
      for hepatocarcinogenesis.

PMID- 21173814
TI  - Simple dispersion law for arbitrary sequences of dispersive optics.
AB  - We give a simple general formula for the total angular dispersion due to multiple
      arbitrary dispersive elements in a series. It is simply the sum of the individual
      elements' angular dispersions but with each divided by the total spatial
      magnification afterward (or, equivalently, multiplied by the total angular
      magnification afterward).

PMID- 21173813
TI  - High-resolution terahertz reflective imaging and image restoration.
AB  - We present a high-resolution terahertz (THz) reflective imaging system, operating
      at 2.52 THz, that employs a continuous-wave THz gas laser and a pyroelectric
      detector. The spatial resolution was evaluated from the system's modulation
      transfer function and tested by scanning a series of resolution targets. To
      further improve the image quality, Lucy-Richardson method was adopted to restore
      the scanning result. With the scanning spot profile measured using knife edge
      method, a satisfying restoration result can be obtained. Finally, the system's
      performance was observed by imaging some different test objects.

PMID- 21173815
TI  - Phase pattern denoising using a regularized cost function with complex-valued
      Markov random fields based on a discrete model.
AB  - We present a simple and effective method for denoising phase patterns based on a
      discrete model. The proposed filtering method transforms the image denoising
      problem to solving the energy diffusion problem of a system with complex-valued
      fields. We establish an appropriate cost function that uses the discrete form of
      complex-valued Markov random fields. The attractiveness of the proposed filtering
      method includes three points: the first is that the filtering process can be
      easily implemented using an iterative method, the second is that 2pi phase jumps
      are well preserved, and the third is its little computational effort. The
      performance of the proposed method is demonstrated by simulated and
      experimentally obtained phase patterns.

PMID- 21173816
TI  - Determination of the photoluminescence quantum yield of diluted dye solutions in
      highly scattering media by pulsed photoacoustic spectroscopy.
AB  - A pulsed photoacoustic system is used to determine the fluorescence quantum yield
      of diluted dye solutions in highly scattering media. In order to show its
      accuracy, the quantum yield of Rhodamine 6G in water and ethanol was calculated.
      The chemical Fuchsin was utilized as a dye reference because the entire
      excitation energy is converted into nonradiative relaxation processes. The
      scattering coefficient of the samples was incremented by using spherical silica
      particles of different sizes and concentrations. The determined mean values in
      the studied scattering optical density range (0-3 cm(-1)) were 0.95 for ethanol
      and 0.96 for water. These measurements are in excellent agreement with the best
      literature values.

PMID- 21173817
TI  - Switchable dual-wavelength single-longitudinal-mode erbium-doped fiber laser
      using an inverse-Gaussian apodized fiber Bragg grating filter and a low-gain
      semiconductor optical amplifier.
AB  - We present a stable and switchable dual-wavelength erbium-doped fiber laser. In
      the ring cavity, an inverse-Gaussian apodized fiber Bragg grating serves as an
      ultranarrow dual-wavelength passband filter, a semiconductor optical amplifier
      biased in the low-gain regime reduces the gain competition of the two
      wavelengths, and a feedback fiber loop acts as a mode filter to guarantee a
      stable single-longitudinal-mode operation. Two lasing lines with a wavelength
      separation of approximately 0.1 nm are obtained experimentally. A microwave
      signal at 12.51 GHz is demonstrated by beating the dual wavelengths at a
      photodetector.

PMID- 21173818
TI  - Fourier analysis for hydrostatic pressure sensing in a polarization-maintaining
      photonic crystal fiber.
AB  - We measured the hydrostatic pressure dependence of the birefringence and
      birefringent dispersion of a Sagnac interferometric sensor incorporating a length
      of highly birefringent photonic crystal fiber using Fourier analysis. Sensitivity
      of both the phase and chirp spectra to hydrostatic pressure is demonstrated.
      Using this analysis, phase-based measurements showed a good linearity with an
      effective sensitivity of 9.45 nm/MPa and an accuracy of +/-7.8 kPa using
      wavelength-encoded data and an effective sensitivity of -55.7 cm(-1)/MPa and an
      accuracy of +/-4.4 kPa using wavenumber-encoded data. Chirp-based measurements,
      though nonlinear in response, showed an improvement in accuracy at certain
      pressure ranges with an accuracy of +/-5.5 kPa for the full range of measured
      pressures using wavelength-encoded data and dropping to within +/-2.5 kPa in the
      range of 0.17 to 0.4 MPa using wavenumber-encoded data. Improvements of the
      accuracy demonstrated the usefulness of implementing chirp-based analysis for
      sensing purposes.

PMID- 21173819
TI  - Cylindrical hybrid plasmonic waveguide for subwavelength confinement of light.
AB  - A novel cylindrical hybrid plasmonic waveguide is proposed to achieve
      subwavelength confinement of light. With a metal core surrounded by a silica
      layer and a silicon layer, the proposed cylindrical hybrid plasmonic waveguide
      can achieve a ring-structure mode profile at the operating wavelength (1550 nm).
      Most mode power locates in the silica layer with a nanoscale thickness (e.g., 50,
      20, or even 5 nm), which is due to the effects of both a strong discontinuity of
      the normal component of the electric field at the silicon-silica interface and
      the exited surface plasmon wave at the silica-metal interface. Cylindrical hybrid
      plasmonic waveguides with different structure parameters are investigated and a
      relatively long propagation distance of tens of micrometers (or even hundreds of
      micrometers) is observed.

PMID- 21173820
TI  - Near-field optical properties of silver nanocylinders arranged in a Pascal
      triangle.
AB  - The Pascal triangle is a geometric representation of binomial coefficients in
      triangular form. We utilize this formalism to deterministically arrange silver
      nanocylinders of different sizes (30, 60, and 90 nm) on a triangle and
      numerically study their near-field optical properties. We show that near-field
      intensities at specific points on this triangle depend on the wavelength and
      angle of incidence. From the wavelength-dependent studies at various junctions of
      nanocylinders, we obtain maximum near-field intensity at 350 and 380 nm. By
      varying the angle of incidence of the TM-polarized plane wave, we find systematic
      variation in the near-field intensity at different junctions of the geometry. Our
      study will lead to insights in designing controllable electromagnetic hot spots
      for chip-based plasmonic devices.

PMID- 21173821
TI  - Microscope system for Blu-ray disc samples.
AB  - We introduce a microscope system using a solid immersion lens (SIL) to image Blu
      ray disc samples without removing the protective cover layer. The aberration
      caused by the cover layer is minimized with a truncated SIL. A subsurface imaging
      simulation is achieved by using the rigorous coupled wave theory, partial
      coherence, vector diffraction, and the Babinet principle. Simulated results are
      compared with experimental images and atomic force microscopy measurements.

PMID- 21173822
TI  - Alternative method for measuring the full-field refractive index of a gradient
      index lens with normal incidence heterodyne interferometry.
AB  - A linearly/circularly polarized heterodyne light beam coming from a heterodyne
      light source with an electro-optic modulator in turn enters a modified Twyman
      Green interferometer to measure the surface plane of a GRIN lens. Two groups of
      periodic sinusoidal segments recorded by a fast complementary metal-oxide
      semiconductor camera are modified, and their associated phases are derived with
      the unique technique. The data are substituted into the special equations derived
      from the Fresnel equations, and the refractive index can be obtained. When the
      processes are applied to other pixels, the full-field refractive-index
      distribution can be obtained similarly. Its validity is demonstrated.

PMID- 21173823
TI  - Catastrophes in wavefront-coding spatial-domain design.
AB  - Spatial-domain design for wavefront-coding systems frequently simplifies the
      defining oscillatory integral of the point spread function (PSF) by means of the
      stationary phase approximation (SPA). Although the SPA applies over much of the
      support of the PSF, it tends to break down at or near the regions of highest
      intensity. A branch of mathematics known as catastrophe theory is shown to
      provide tools that can ferret out important design information precisely at the
      points where the SPA is unphysical.

PMID- 21173824
TI  - Experimental generation of Mathieu-Gauss beams with a phase-only spatial light
      modulator.
AB  - We present a novel method for the efficient generation of even, odd, and helical
      Mathieu-Gauss beams of arbitrary order and ellipticity by means of a phase-only
      spatial light modulator (SLM). Our method consists of displaying the phase of the
      desired beam in the SLM; the reconstructed field is obtained on-axis following a
      spatial filtering process with an annular aperture. The propagation invariance
      and topological properties of the generated beams are investigated numerically
      and experimentally.

PMID- 21173825
TI  - Structural and optical behavior due to thermal effects in end-pumped Yb:YAG disk
      lasers.
AB  - We employ a Monte Carlo ray-tracing code along with the ANSYS package to predict
      the optical and structural behavior in end-pumped CW Yb:YAG disk lasers. The
      presence of inhomogeneous temperature, stress, and strain distributions is
      responsible for many deleterious effects for laser action through disk fracture,
      strain-induced birefringence, and thermal lensing. The thermal lensing, in turn,
      results in the optical phase distortion in solid-state lasers. Furthermore, the
      dependence of optical phase distortion on variables such as the heat transfer
      coefficient, the cooling fluid temperature, and crystal thickness is discussed.

PMID- 21173826
TI  - Influence and compensation of autocorrelation terms in depth-resolved
      spectroscopic Fourier-domain optical coherence tomography.
AB  - We demonstrate depth-resolved spectral absorption measurements in the wavelength
      range from 750 to 850 nm using a broadband light source consisting of three
      spectrally shifted superluminescent light-emitting diode modules and a low-cost
      spectrometer-based Fourier-domain optical coherence tomography system. We present
      the theoretical model and experimental verification of interferences between
      autocorrelation terms and the signal carrying cross-correlation terms, strongly
      affecting the absorption measurements. A simple background subtraction,
      minimizing the artifacts caused by the interferences of autocorrelation and cross
      correlation terms, is presented.

PMID- 21173827
TI  - Orthonormal aberration polynomials for anamorphic optical imaging systems with
      rectangular pupils.
AB  - The classical aberrations of an anamorphic optical imaging system, representing
      the terms of a power-series expansion of its aberration function, are separable
      in the Cartesian coordinates of a point on its pupil. We discuss the balancing of
      a classical aberration of a certain order with one or more such aberrations of
      lower order to minimize its variance across a rectangular pupil of such a system.
      We show that the balanced aberrations are the products of two Legendre
      polynomials, one for each of the two Cartesian coordinates of the pupil point.
      The compound Legendre polynomials are orthogonal across a rectangular pupil and,
      like the classical aberrations, are inherently separable in the Cartesian
      coordinates of the pupil point. They are different from the balanced aberrations
      and the corresponding orthogonal polynomials for a system with rotational
      symmetry but a rectangular pupil.

PMID- 21173828
TI  - Efficient reconstruction method for L1 regularization in fluorescence molecular
      tomography.
AB  - Fluorescence molecular tomography (FMT) is a promising technique for in vivo
      small animal imaging. In this paper, the sparsity of the fluorescent sources is
      considered as the a priori information and is promoted by incorporating L1
      regularization. Then a reconstruction algorithm based on stagewise orthogonal
      matching pursuit is proposed, which treats the FMT problem as the basis pursuit
      problem. To evaluate this method, we compare it to the iterated-shrinkage-based
      algorithm with L1 regularization. Numerical simulations and physical experiments
      show that the proposed method can obtain comparable or even slightly better
      results. More importantly, the proposed method was at least 2 orders of magnitude
      faster in these experiments, which makes it a practical reconstruction algorithm.

PMID- 21173830
TI  - Reduction of the pump power threshold in the nonlinear all-optical photonic
      crystal directional coupler switches.
AB  - In this paper, the cross-phase modulation Kerr nonlinear effect is utilized to
      induce nonlinearity and a change in the coupling length by a high-intensity pump
      signal in the nonlinear photonic crystal directional coupler. We have analyzed
      and modified the nonlinear square-lattice directional couplers for the first
      time, to the best of our knowledge, and have improved the power consumption for
      inducing the nonlinear switching. We have shown that according to the slower
      group velocity and the increased confinement of the TM modes with lower frequency
      in the region with a higher dielectric constant in a square lattice, the required
      switching pump power of the structure is less than that of the same triangular
      structure.

PMID- 21173829
TI  - Optothermophysical properties of demineralized human dental enamel determined
      using photothermally generated diffuse photon density and thermal-wave fields.
AB  - Noninvasive dental diagnostics is a growing discipline since it has been
      established that early detection and quantification of tooth mineral loss can
      reverse caries lesions in their incipient state. A theoretical coupled diffuse
      photon density and thermal-wave model was developed and applied to photothermal
      radiometric frequency responses, fitted to experimental data using a
      multiparameter simplex downhill minimization algorithm for the extraction of
      optothermophysical properties from artificially demineralized human enamel. The
      aim of this study was to evaluate the reliability and robustness of the advanced
      fitting algorithm. The results showed a select group of optical and thermal
      transport parameters and thicknesses were reliably extracted from the
      computational fitting algorithm. Theoretically derived thicknesses were
      accurately predicted, within about 20% error, while the estimated error in the
      optical and thermal property evaluation was within the values determined from
      early studies using destructive analyses. The high fidelity of the theoretical
      model illustrates its efficacy, reliability, and applicability toward the
      nondestructive characterization of depthwise inhomogeneous sound enamel and
      complex enamel caries lesions.

PMID- 21173831
TI  - Iodine-filter-based mobile Doppler lidar to make continuous and full-azimuth
      scanned wind measurements: data acquisition and analysis system, data retrieval
      methods, and error analysis.
AB  - An incoherent Doppler wind lidar based on iodine edge filters has been developed
      at the Ocean University of China for remote measurements of atmospheric wind
      fields. The lidar is compact enough to fit in a minivan for mobile deployment.
      With its sophisticated and user-friendly data acquisition and analysis system
      (DAAS), this lidar has made a variety of line-of-sight (LOS) wind measurements in
      different operational modes. Through carefully developed data retrieval
      procedures, various wind products are provided by the lidar, including wind
      profile, LOS wind velocities in plan position indicator (PPI) and range height
      indicator (RHI) modes, and sea surface wind. Data are processed and displayed in
      real time, and continuous wind measurements have been demonstrated for as many as
      16 days. Full-azimuth-scanned wind measurements in PPI mode and full-elevation
      scanned wind measurements in RHI mode have been achieved with this lidar. The
      detection range of LOS wind velocity PPI and RHI reaches 8-10 km at night and 6-8
      km during daytime with range resolution of 10 m and temporal resolution of 3 min.
      In this paper, we introduce the DAAS architecture and describe the data retrieval
      methods for various operation modes. We present the measurement procedures and
      results of LOS wind velocities in PPI and RHI scans along with wind profiles
      obtained by Doppler beam swing. The sea surface wind measured for the sailing
      competition during the 2008 Beijing Olympics is also presented. The precision and
      accuracy of wind measurements are estimated through analysis of the random errors
      associated with photon noise and the systematic errors introduced by the
      assumptions made in data retrieval. The three assumptions of horizontal
      homogeneity of atmosphere, close-to-zero vertical wind, and uniform sensitivity
      are made in order to experimentally determine the zero wind ratio and the
      measurement sensitivity, which are important factors in LOS wind retrieval.
      Deviations may occur under certain meteorological conditions, leading to bias in
      these situations. Based on the error analyses and measurement results, we point
      out the application ranges of this Doppler lidar and propose several paths for
      future improvement.

PMID- 21173832
TI  - Controlling the polarization dependence of dual-channel directional couplers
      formed by silicon-on-insulator slot waveguides.
AB  - The polarization dependence of directional couplers (DC) formed by silicon-on
      insulator (SOI) slot waveguides was studied, and its applications as highly
      efficient polarization beam splitters (PBSs) and polarization-independent
      directional couplers (PIDCs) were investigated. The coupling lengths for the
      quasi-TE and quasi-TM modes may vary with the waveguide geometry due to
      structural birefringence; thus numerical simulations of the coupling effects in
      the directional couplers with different aspect ratios and waveguide spacing were
      conducted to obtain the optimal design parameters for high efficiency as well as
      compact device size. The lengths of the coupling regions of the designed PBS and
      PIDC are 47.61 and 23.13 MUm, respectively, and they delivered good performance,
      with an extinction ratio greater than 20 and 1 dB bandwidth larger than 100 nm.
      The tolerance of fabrication error in the practical device is also discussed.

PMID- 21173833
TI  - Dynamic optically reconfigurable gate array very large-scale integration with
      partial reconfiguration capability.
AB  - We present a proposal of a partial reconfiguration architecture for optically
      reconfigurable gate arrays and present an 11,424 gate dynamic optically
      reconfigurable gate array VLSI chip that was fabricated on a 96.04 mm(2) chip
      using an 0.35 MUm three-metal complementary metal oxide semiconductor process
      technology. The fabricated VLSI chip achieved a 2.21 MUs partial reconfiguration.

PMID- 21173834
TI  - Polarization lidar for shallow water depth measurement.
AB  - A bathymetric, polarization lidar system transmitting at 532 nm and using a
      single photomultiplier tube is employed for applications of shallow water depth
      measurement. The technique exploits polarization attributes of the probed water
      body to isolate surface and floor returns, enabling constant fraction detection
      schemes to determine depth. The minimum resolvable water depth is no longer
      dictated by the system's laser or detector pulse width and can achieve better
      than 1 order of magnitude improvement over current water depth determination
      techniques. In laboratory tests, an Nd:YAG microchip laser coupled with
      polarization optics, a photomultiplier tube, a constant fraction discriminator,
      and a time-to-digital converter are used to target various water depths with an
      ice floor to simulate a glacial meltpond. Measurement of 1 cm water depths with
      an uncertainty of +/-3 mm are demonstrated using the technique. This novel
      approach enables new approaches to designing laser bathymetry systems for shallow
      depth determination from remote platforms while not compromising deep water depth
      measurement.

PMID- 21173835
TI  - Control of elevated blood pressure in acute intracerebral hemorrhage.
AB  - Intracerebral hemorrhage remains a challenging worldwide clinical problem with no
      proven treatments. In the acute phase of the illness, there has been some
      controversy regarding the appropriate management of elevated blood pressure.
      Recently published and ongoing clinical trials are beginning to shed some light
      on appropriate blood pressure management in acute intracerebral hemorrhage. This
      brief review focuses on these trials. In the next few years, it is hoped that
      clinical uncertainty regarding this issue will be obviated after completion of
      these trials.

PMID- 21173836
TI  - Beta cell antigens in type 1 diabetes: triggers in pathogenesis and therapeutic
      targets.
AB  - Recognition of pancreatic beta cell antigens by autoreactive T lymphocytes plays
      a central role in the pathogenesis of insulin-dependent type 1 diabetes. Recent
      results suggest that non-conventional antigenic epitope processing and
      presentation may contribute to triggering and maintaining autoreactive responses.
      Moreover, promising results raise hope that autoantigens may become safe and
      specific therapeutics for type 1 diabetes in the future.

PMID- 21173837
TI  - The unexpandable lung.
AB  - Unexpandable lung is the inability of the lung to expand to the chest wall
      allowing for normal visceral and parietal pleural apposition. It is the direct
      result of either pleural disease, endobronchial obstruction resulting in lobar
      collapse, or chronic atelectasis. Unexpandable lung occurring as a consequence of
      active or remote pleural disease may present as a post-thoracentesis
      hydropneumothorax or an effusion that cannot be completely drained because of the
      development of anterior chest pain. Pleural manometry is useful for identifying
      unexpandable lung during initial pleural drainage. Unexpandable lung occurring as
      a consequence of active or remote pleural disease may be separated into two
      distinct clinical entities termed trapped lung and lung entrapment. Trapped lung
      is a diagnosis proper and is caused by the formation of a fibrous visceral
      pleural peel (in the absence of malignancy or active pleural inflammation). The
      mechanical effect of the pleural peel constitutes the primary clinical problem.
      Lung entrapment may result from a visceral pleural peel secondary to active
      pleural inflammation, infection, or malignancy. In these cases, the underlying
      malignant or inflammatory condition is the primary clinical problem, which may or
      may not be complicated by unexpandable lung due to visceral pleural involvement.
      The recognition of trapped lung and lung entrapment as related, but distinct,
      clinical entities has direct consequences on clinical management. In our
      practice, pleural manometry is routinely performed during therapeutic
      thoracentesis and is useful for identification of unexpandable lung and has
      allowed us to understand the mechanisms surrounding a post-thoracentesis
      pneumothorax.

PMID- 21173838
TI  - Recent advances in the assessment and treatment of falls in Parkinson's disease.
AB  - Falls are among the most incapacitating features of Parkinson's disease.
      Prevention of falls requires a systematic assessment of all contributing factors
      (with emphasis on freezing of gait and frontal executive dysfunction), and a
      multidisciplinary treatment approach tailored to the specific pathophysiology of
      falls for each individual patient.

PMID- 21173839
TI  - Treating aging: progress toward dietary restriction mimetics.
AB  - During the last decade, biogerontologists have labored to understand the
      biological basis of the aging process by studying the genes and signaling
      pathways that regulate it. But the last year has seen a breakthrough in a
      different direction: toward treatments that might slow aging by mimicking the
      effects of dietary restriction.

PMID- 21173840
TI  - Role of endoplasmic reticulum domains in determining secretion routes.
AB  - Distinct domains of the endoplasmic reticulum (ER) can function as entry points
      into different protein-sorting routes. In addition to using the classical ER
      Golgi pathway, one of these unconventional routes utilizes different combinations
      of machinery of the classical secretory pathway and components of the
      autophagosomal system.

PMID- 21173841
TI  - Self-incompatibility.
AB  - There are several different types of self-incompatibility in different flowering
      plant species, and there has recently been progress in understanding their
      molecular genetics by using combined molecular and evolutionary approaches.
      Questions include the mechanism of self-incompatibility (both the nature of the
      proteins encoded by the genes and whether incompatibility systems all have
      separate genes for the pollen and pistil recognition proteins, which is the focus
      of this mini-review) and whether these systems involve chromosome regions with
      suppressed recombination and, if so, the size of these regions.

PMID- 21173842
TI  - Hebb and the art of spine remodeling.
AB  - The notion that synaptic remodeling underlies certain forms of learning is one of
      the main tenets of Hebb's inspiring theories dating from the 1940s. Until
      recently, however, direct evidence for tight relationships between synaptic
      remodeling and behavior has been scarce. Fascinating data from recent studies on
      the remodeling of postsynaptic structures known as dendritic spines indicates
      that such relationships might be more complex than initially expected.

PMID- 21173843
TI  - Do PAKs make good drug targets?
AB  - p21-activated kinases (PAKs) act downstream of Rho-family GTPase and are linked
      to steps in both cancer initiation and progression. There are six mammalian PAK
      isoforms that are divided into two groups, and for different reasons both groups
      are attractive targets for cancer therapy. We describe the background and recent
      development of a PAK inhibitor, PF-3758309, which exhibits relatively good
      selectivity and high potency for PAKs. Experiments using PF-3758309 confirm that
      inhibiting PAK is a beneficial strategy to combat some tumors, and this activity
      is likely related to modulation of both cell proliferation and survival. The
      genetic loss of NF2 (neurofibromatosis type 2) leading to increased cell
      proliferation through a Ras-Rac-PAK pathway may represent a good test system to
      analyze this new PAK inhibitor.

PMID- 21173844
TI  - Coral reefs in crisis: reversing the biotic death spiral.
AB  - Coral reefs are disappearing due to global warming, overfishing, ocean
      acidification, pollution, and interactions of these and other stresses.
      Ecologically informed management of fishes that facilitate corals by suppressing
      seaweeds may be our best bet for bringing reefs back from the brink of
      extinction.

PMID- 21173845
TI  - New genetic resources for mammalian developmental biologists.
AB  - The utilization of homologous recombination in embryonic stem cells as a means to
      generate mice carrying pre-determined modifications of genomic sequences has
      revolutionized the study of developmental biology. Recognizing the potential
      efficiencies that can be obtained by high-throughput production at centralized
      technology centers, a number of large-scale efforts for generating mice with
      targeted mutations have been funded. These programs are reaching fruition, and a
      variety of libraries of embryonic stem cells with defined mutations are now
      available.

PMID- 21173846
TI  - All for one, and one for all: the clonality of the intestinal stem cell niche.
AB  - Intestinal epithelia are maintained by intestinal stem cells (ISCs) that divide
      to replace dying absorptive and secretory cells that make up this tissue. Lineage
      labeling studies, both in vertebrates and Drosophila, have revealed the
      relationships between ISCs and their progeny. In addition, a number of signaling
      pathways involved in ISC proliferation and differentiation have been identified.
      Further studies will clarify the signals originating from the ISC niche and
      determine the processes that control the number and uniform distribution of
      niches throughout the epithelium.

PMID- 21173847
TI  - How do RNA sequence, DNA sequence, and chromatin properties regulate splicing?
AB  - Recent genome-wide studies have revealed a remarkable correspondence between
      nucleosome positions and exon-intron boundaries, and several studies have
      implicated specific histone modifications in regulating alternative splicing. In
      addition, recent progress in cracking the 'splicing code' shows that sequence
      motifs carried on the nascent RNA molecule itself are sufficient to accurately
      predict tissue-specific alternative splicing patterns. Together, these studies
      shed light on the complex interplay between RNA sequence, DNA sequence, and
      chromatin properties in regulating splicing.

PMID- 21173848
TI  - Antigen processing for MHC presentation by autophagy.
AB  - Autophagy delivers cytoplasmic constituents for lysosomal degradation. This
      catabolic pathway can be used to deliver intracellular antigens for major
      histocompatibility complex (MHC) class II presentation. In addition, recent
      evidence suggests that it also facilitates the processing of extracellular
      antigens for both MHC class I and II presentation.

PMID- 21173849
TI  - Advances in epilepsy: new perspectives on new-onset epilepsy, comorbidities, and
      pharmacotherapy.
AB  - The purpose of this brief article is to review old concepts of the significance
      of acute symptomatic seizures, the impact of psychiatric comorbidities on the
      response of pharmacologic and surgical treatments of the seizure disorder, and
      the importance of factoring comorbid medical comorbidities into the choice of
      antiepileptic drugs (AEDs). In addition, this article provides an update on the
      latest data on the teratogenic effects of AEDs and reviews the most relevant
      results of a recent practice guideline on pregnancy issues in women with
      epilepsy. The article closes with a review of the latest advances in the
      therapeutic effects of first- and second-generation AEDs.

PMID- 21173850
TI  - Recent advances in the treatment of pain.
AB  - Cancer pain and chronic non-malignant pain can be difficult to manage and may not
      respond satisfactorily to standard analgesics. Sequential empiric analgesic
      trials are usually done to manage individual patients. Experimental human pain
      models have helped to clarify mechanisms of opioid and adjuvant analgesic
      actions. Combinations of opioids and adjuvant analgesics better relieve pain than
      either opioids or adjuvant analgesics alone, as demonstrated in randomized
      controlled trials. The analgesic activity of antidepressants is largely dependent
      upon norepinephrine reuptake and activation of alpha 2 adrenergic receptors.
      Corticosteroids reduce postoperative orthopedic incident pain, which may allow
      patients to ambulate earlier and with less pain. Spinal corticosteroids reduce
      lower hemibody pain. Gabapentinoids as single high doses reduce postoperative
      pain and certain acute pain syndromes. Individuals who experience flares of pain
      while on spinal opioids benefit from intrathecal boluses of levobupivicaine or
      sublingual ketamine. Interventional approaches to pain management are often
      necessary due to the limitations of systemic analgesics. Electronics stimulators
      (peripheral, spinal and motor cortex) improve difficult to manage chronic pain
      syndromes. Pulsed radiofrequency reduces pain without tissue damage, which could
      be an advantage over chemical or radiofrequency neurotomy. Botulinum toxin A
      reduces focal neuropathic pain that is durable. Interventional related successes
      in relieving pain are operator dependent. Most reported benefits of systemic and
      regional analgesics and interventional approaches to pain relief are not based on
      randomized trials and are subject to selection bias, sampling error, and placebo
      responses, which may over-inflate reported benefits. Randomized controlled trials
      are needed to confirm reported benefits.

PMID- 21173851
TI  - Roles of ADF/cofilin in actin polymerization and beyond.
AB  - In collaboration or competition with many other actin-binding proteins, the actin
      depolymerizing factor/cofilins integrate transmembrane signals to coordinate the
      spatial and temporal organization of actin filament assembly/disassembly
      (dynamics). In addition, newly discovered effects of these proteins in lipid
      metabolism, gene regulation, and apoptosis suggest that their roles go well
      beyond regulating the cytoskeleton.

PMID- 21173852
TI  - Relationships between mild traumatic brain injury sustained in combat and post
      traumatic stress disorder.
AB  - The setting of the trauma is a distinguishing feature between mild traumatic
      brain injury (mTBI; also called concussion) that occurs in civilian settings
      compared with that occurring in combat. Combat mTBI is frequently associated with
      a prolonged stress reaction, post-traumatic stress disorder (PTSD). Individuals
      with mTBI and PTSD from combat in Operations Iraqi Freedom and Enduring Freedom
      often develop prolonged post-concussion symptoms (PCSs) such as headache. Both
      mTBI and PTSD may contribute to PCSs. PTSD may worsen and prolong the PCSs
      following mTBI by disrupting sleep. It is not known how mTBI predisposes an
      individual to develop PTSD.

PMID- 21173854
TI  - Pharmacogenetics of osteoporosis.
AB  - Osteoporosis is a complex bone disorder with a strong genetic basis. The genetics
      of osteoporosis encompasses two main areas: genetics of disease susceptibility
      and pharmacogenetics of drug response. The former has been widely studied in the
      past few decades, while the latter is still largely untouched. This review will
      provide an overview of the pharmacogenetics of osteoporosis, focusing on the
      major recent advances in the past two years.

PMID- 21173853
TI  - Advances in the prevention, management, and treatment of community-acquired
      pneumonia.
AB  - Despite the availability of powerful antibiotics, community-acquired pneumonia
      (CAP) remains one of the leading reasons for morbidity and mortality worldwide,
      and despite the availability of powerful antibiotics, there has been only little
      improvement in case fatality rates for many years. Consequently, it cannot be
      expected that novel antibiotics will substantially improve outcomes in CAP.
      Therefore, this review focuses on novel approaches that may reduce CAP-related
      mortality: the impact of immunomodulation by macrolides and fluoroquinolones and
      the prevention of CAP by pneumococcal vaccines.

PMID- 21173855
TI  - Recent advances in RNA sequence analysis.
AB  - The latest high-throughput DNA sequencing technology can now be applied on a
      large scale to capture the complete set of mRNA transcripts in a cell, using a
      technique called RNA-seq. Although RNA-seq is only 2 years old, it has rapidly
      swept through the field of genomics, and it is now being used to analyze the
      transcriptomes of organisms ranging from bacteria to primates. The depth of
      sequencing allows researchers to quantify the level of expression of genes, to
      discover alternative isoforms in eukaryotic species, and even to characterize the
      operon structure of bacterial genomes.

PMID- 21173856
TI  - Management of acromegaly.
AB  - Acromegaly is caused by hypersecretion of growth hormone and resultant
      overproduction of insulin-like growth factor-1 and is associated with increased
      mortality and morbidity. Successful treatment modalities have been developed and
      are used in a multistep approach allowing normal life expectancy as well as
      improved quality of life in an increasing number of patients.

PMID- 21173857
TI  - What drives corticospinal output?
AB  - Recent work has not only defined the origin of the direct cortico-motoneuronal
      output to the upper limb but has also identified some of the cortical networks
      that engage the corticospinal output during movement. A surprising finding is
      that some corticospinal neurons show 'mirror-like' properties and are actively
      modulated not only during self-movement but also during action observation.

PMID- 21173858
TI  - Modelling ecosystem services in terrestrial systems.
AB  - Over the past few decades, a multi-disciplinary research community has documented
      the goods and services provided by ecosystems in specific sites scattered across
      the world. This research community has now begun to focus on creating methods and
      tools for mapping and valuing the ecosystem services produced on any landscape in
      the world. We describe some of these methods and tools and how they calculate and
      express ecosystem service provision and value on landscapes. We also describe
      methods for predicting landscape change. These predictions can be used by multi
      ecosystem service models to assess potential changes and trade-offs in ecosystem
      service provision and values into the future.

PMID- 21173859
TI  - Recent advances in preventing cardiovascular disorders by managing lipid levels.
AB  - Advances in clinical lipidology during the last 18 months include the
      establishment of high-sensitivity C-reactive protein (hsCRP) as an important risk
      marker for cardiovascular disease. Determining hsCRP levels should help the
      clinician single out patients at particularly high risk. However, more research
      needs to be done in this area. Furthermore, statins do not seem to be of benefit
      in patients with severe congestive heart failure, on chronic hemodialysis, or
      with aortic stenosis. Next, plasma triglyceride levels are now considered an
      important risk marker for cardiovascular disease, but the therapeutic benefits
      related to lowering triglyceride levels remain difficult to achieve. Also,
      nicotinic acid has gained more interest partly because recent studies have
      demonstrated positive effects on atherosclerosis development and partly because
      the side effect of flushing seems to be partially avoidable with the concomitant
      administration of laropiprant. Both the raising of high-density lipoprotein
      cholesterol by nicotinic acid and the additional lowering of low-density
      lipoprotein cholesterol by ezetimibe and eprotirome will need to demonstrate hard
      endpoint reductions in large-scale intervention trials. Trials of
      niacin/laropiprant (the AIM-HIGH and HPS2-THRIVE studies) and ezetimibe (the
      IMPROVE-IT study) are already under way.

PMID- 21173860
TI  - Characterizing changes in marine ecosystem services.
AB  - The benefits of marine ecosystems for people are increasingly being characterized
      through the concept of ecosystem services, with the promise to aid decision
      making from marine spatial planning to ecosystem-based management. The
      characterization of changes in marine ecosystem services is central to the
      application of ecological science to policy contexts, and this field is quickly
      evolving with innovations in frameworks for integrating science, understanding of
      ecosystems and human benefits, and innovations in tools for the modeling of
      services. In this article, we review efforts to characterize changes in marine
      ecosystem services, including recent advances, and we propose five key future
      directions for research: cultural values, qualitative or semi-quantitative
      modeling approaches, cumulative impacts, model evaluation, and markets.

PMID- 21173861
TI  - The timing of surgical decompression for spinal cord injury.
AB  - Research into the pathophysiological mechanisms of spinal cord injury (SCI) has
      resulted in a classification scheme of primary and secondary injury. Primary
      injury refers to the destructive nature of the initial impact and the subsequent
      shearing, penetrating, and compressive forces that injure the delicate neural
      tissue. Secondary injury refers to a complex array of pathophysiologial processes
      - including ischemia, inflammation, excitotoxicity, and oxidative cell damage -
      that contribute to the ultimate loss of neural tissue. While our understanding of
      secondary mechanisms improves with continued research, novel treatments for SCI
      are currently being developed with a foundation rooted in halting deleterious
      secondary mechanisms. In this article, we will review the current evidence for
      surgical decompression as a treatment for SCI. Emerging evidence and a growing
      consensus among surgeons are in support of early surgical intervention to help
      minimize the secondary damage caused by compression of the spinal cord after
      trauma.

PMID- 21173862
TI  - Tissue engineering in urethral reconstruction.
AB  - Tissue engineering is an exciting and rapidly evolving technology. In this
      review, we discuss the recent progress made in the field of urethral
      reconstruction and consider the clinical implications and further advancement of
      these endeavours.

PMID- 21173863
TI  - Clinical applications of breath testing.
AB  - Breath testing has the potential to benefit the medical field as a cost
      effective, non-invasive diagnostic tool for diseases of the lung and beyond. With
      growing evidence of clinical worth, standardization of methods, and new sensor
      and detection technologies the stage is set for breath testing to gain
      considerable attention and wider application in upcoming years.

PMID- 21173866
TI  - Lensfree color imaging on a nanostructured chip using compressive decoding.
AB  - We demonstrate subpixel level color imaging capability on a lensfree incoherent
      on-chip microscopy platform. By using a nanostructured substrate, the incoherent
      emission from the object plane is modulated to create a unique far-field
      diffraction pattern corresponding to each point at the object plane. These
      lensfree diffraction patterns are then sampled in the far-field using a color
      sensor-array, where the pixels have three different types of color filters at
      red, green, and blue (RGB) wavelengths. The recorded RGB diffraction patterns
      (for each point on the structured substrate) form a basis that can be used to
      rapidly reconstruct any arbitrary multicolor incoherent object distribution at
      subpixel resolution, using a compressive sampling algorithm. This lensfree
      computational imaging platform could be quite useful to create a compact
      fluorescent on-chip microscope that has color imaging capability.

PMID- 21173864
TI  - Unmasking the acoustic effects of vowel-to-vowel coarticulation: A statistical
      modeling approach.
AB  - Coarticulation is a source of acoustic variability for vowels, but how large is
      this effect relative to other sources of variance? We investigate acoustic
      effects of anticipatory V-to-V coarticulation relative to variation due to the
      following C and individual speaker. We examine F1 and F2 from V1 in 48 V1-C#V2
      contexts produced by 10 speakers of American English. ANOVA reveals significant
      effects of both V2 and C on F1 and F2 measures of V1. The influence of V2 and C
      on acoustic variability relative to that of speaker and target vowel identity is
      evaluated using hierarchical linear regression. Speaker and target vowel account
      for roughly 80% of the total variance in F1 and F2, but when this variance is
      partialed out C and V2 account for another 18% (F1) and 63% (F2) of the remaining
      target vowel variability. Multinomial logistic regression (MLR) models are
      constructed to test the power of target vowel F1 and F2 for predicting C and V2
      of the upcoming context. Prediction accuracy is 58% for C-Place, 76% for C
      Voicing and 54% for V2, but only when variance due to other sources is factored
      out. MLR is discussed as a model of the parsing mechanism in speech perception.

PMID- 21173867
TI  - Fungal echinocandin resistance.
AB  - Echinocandins are the most recent introduction to the antifungal armamentarium
      and target the synthesis of beta-(1,3)-glucan, the major structural
      polysaccharide of the fungal cell wall. Mechanisms have been identified that
      reduce the efficacy of the echinocandins: mutations of the Fks subunit of the
      target enzyme complex or a compensatory increase in the production of chitin, the
      second structural cell wall polysaccharide.

PMID- 21173869
TI  - Spindle checkpoint silencing: ensuring rapid and concerted anaphase onset.
AB  - The spindle checkpoint delays anaphase onset in the presence of defective
      kinetochore-microtubule attachments. Such delays can last for just a few minutes
      or several hours, but very shortly after all chromosomes achieve bi-orientation,
      a remarkably synchronous anaphase ensues. We are beginning to understand the
      pathways involved in silencing spindle checkpoint signals and subsequent
      activation of the anaphase-promoting complex. Here, we review recent advances
      made in our understanding of the molecular mechanisms regulating this critical
      cell cycle transition.

PMID- 21173868
TI  - Optimizing root system architecture in biofuel crops for sustainable energy
      production and soil carbon sequestration.
AB  - Root system architecture (RSA) describes the dynamic spatial configuration of
      different types and ages of roots in a plant, which allows adaptation to
      different environments. Modifications in RSA enhance agronomic traits in crops
      and have been implicated in soil organic carbon content. Together, these
      fundamental properties of RSA contribute to the net carbon balance and overall
      sustainability of biofuels. In this article, we will review recent data
      supporting carbon sequestration by biofuel crops, highlight current progress in
      studying RSA, and discuss future opportunities for optimizing RSA for biofuel
      production and soil carbon sequestration.

PMID- 21173870
TI  - Developing brain and general anesthesia - is there a cause for concern?
AB  - Skilled management of sick premature babies and very young children has resulted
      in numerous exposures of their brains to a variety of anesthetic agents designed
      to achieve the substantial depth of neuronal inhibition required for complete
      loss of consciousness and insensitivity to pain. Unfortunately, our recent animal
      findings suggest that commonly used general anesthetics are damaging to
      developing neurons and cause significant neuronal deletion in vulnerable brain
      regions. In addition, emerging animal and human data suggest an association
      between early exposure to general anesthesia and long-term impairment of
      cognitive development. Consequently, the prudence of frequent anesthesia exposure
      of this population is now being scrutinized. It is important to note that on the
      basis of currently available information, there are still considerable
      differences of opinion regarding the clinical relevance of the animal findings.
      Since there is insufficient evidence establishing a clear association between
      animal and human findings, it would be premature to suggest major changes in
      current clinical practice.

PMID- 21173871
TI  - On diagnostic blocks for lumbar zygapophysial joint pain.
AB  - Diagnostic blocks are used to identify patients with back pain stemming from
      their lumbar zygapophysial joints. Single, diagnostic blocks have an unacceptably
      high false positive rate. As well, comparative local anaesthetic blocks lack
      validity because the prevalence of the condition is low. Relying on 50% relief
      following single-diagnostic blocks does not provide a valid diagnosis. Placebo
      controlled blocks are the only available valid means of establishing a diagnosis
      of lumbar zygapophysial joint pain.

PMID- 21173872
TI  - Recent advances in hormonal contraception.
AB  - This report reviews some of the new studies regarding new hormonal contraceptive
      formulations (e.g., Yaz, Qlaira((r)), extended-cycle or continuous combined
      contraceptives, subcutaneous depot medroxyprogesterone acetate, and ulipristal
      acetate as an emergency contraceptive). Recent data on the relationship between
      hormonal contraceptive use and bone health are also reviewed.

PMID- 21173873
TI  - Why do oligodendrocyte lineage cells express glutamate receptors?
AB  - The function of glutamate receptors on oligodendrocytes and their precursor cells
      is poorly understood, with their only clear action being to damage these cells in
      pathological conditions. Here we review recent studies of glutamate signalling to
      oligodendrocyte lineage cells, and explore what its physiological function may
      be.

PMID- 21173874
TI  - Is there evidence for a set point that regulates human body weight?
AB  - There is evidence for the idea that there is biological (active) control of body
      weight at a given set point. Body weight is the product of genetic effects (DNA),
      epigenetic effects (heritable traits that do not involve changes in DNA), and the
      environment. Regulation of body weight is asymmetric, being more effective in
      response to weight loss than to weight gain. However, regulation may be lost or
      camouflaged by Western diets, suggesting that the failure of biological control
      is due mainly to external factors. In this situation, the body's 'set point'
      (i.e., a constant 'body-inherent' weight regulated by a proportional feedback
      control system) is replaced by various 'settling points' that are influenced by
      energy and macronutrient intake in order for the body to achieve a zero energy
      balance. In a world of abundance, a prudent lifestyle and thus cognitive control
      are preconditions of effective biological control and a stable body weight. This
      idea also impacts future genetic research on body weight regulation. Searching
      for the genetic background of excess weight gain in a world of abundance is
      misleading since the possible biological control is widely overshadowed by the
      effect of the environment. In regard to clinical practice, dietary approaches to
      both weight loss and weight gain have to be reconsidered. In underweight patients
      (e.g., patients with anorexia nervosa), weight gain is supported by biological
      mechanisms that may or may not be suppressed by hyperalimentation. To overcome
      weight loss-induced counter-regulation in the overweight, biological signals have
      to be taken into account. Computational modeling of weight changes based on
      metabolic flux and its regulation will provide future strategies for clinical
      nutrition.

PMID- 21173875
TI  - Plk4/SAK/ZYG-1 in the regulation of centriole duplication.
AB  - Centrioles organize both centrosomes and cilia. Centriole duplication is tightly
      regulated and coordinated with the cell cycle to limit duplication to only once
      per cell cycle. Defects in centriole number and structure are commonly found in
      cancer. Plk4/SAK and the functionally related Caenorhabditis elegans ZYG-1
      kinases initiate centriole duplication. Several recent studies have elucidated
      the regulated activity of these kinases and potential downstream targets for
      centriole assembly.

PMID- 21173876
TI  - Novel roles for IL-15 in T cell survival.
AB  - Interleukin-15 (IL-15) is generally considered to be a regulator of T cell
      homeostasis because it works with other common gamma-chain cytokines like IL-2
      and IL-7 to control the maintenance of naive and memory T cell populations.
      However, recent reports highlight new roles for IL-15 during the primary immune
      responses that involve promoting the survival of antigen-specific CD8(+) T cells.
      These findings illuminate a previously unanticipated role for IL-15 in the
      generation and resolution of the effector CD8(+) T cell response to pathogens.

PMID- 21173878
TI  - The application of massively parallel sequencing technologies in diagnostics.
AB  - Massively parallel sequencing (MPS) is rapidly evolving and is starting to be
      utilized by the clinical field as well as diagnostics. We describe major recent
      advances that have come about as a result of the application of MPS in the
      biomedical field and the first approaches in medical genetics that have made use
      of MPS. Without any doubt, MPS has proven to be a very powerful technique. To
      unravel the capabilities of MPS for patient care, the most important aspect for
      the acceptance of MPS within clinics and diagnostics is to guarantee that the
      large amount of data undergoes vitally important analyses and interpretation and
      is securely managed.

PMID- 21173877
TI  - New methods for diagnosis and treatment of vestibular diseases.
AB  - Dizziness and vertigo are common complaints, with a lifetime prevalence of over
      30%. This review provides a brief summary of the recent diagnostic and
      therapeutic advances in the field of neuro-otology. A special focus is placed on
      the clinical usefulness of vestibular tests. While these have markedly improved
      over the years, treatment options for vestibular disorders still remain limited.
      Available therapies for selected vestibular diseases are discussed.

PMID- 21173879
TI  - Advances in laryngoscopy: rigid indirect laryngoscopy.
AB  - There is a growing body of evidence to support the use of rigid indirect
      laryngoscopy or 'video' laryngoscopy for tracheal intubation. We summarise some
      of the key issues, comparing rigid indirect laryngoscopy with direct conventional
      laryngoscopy.

PMID- 21173880
TI  - New templates for HIV-1 antibody-based vaccine design.
AB  - A current strategy for the design of neutralizing antibody-based vaccines to
      prevent HIV-1 transmission is that of reverse engineering, starting from a
      neutralizing antibody and working back to reconstruct its epitope by structure
      based design technology. However, the field has been impeded by a lack of
      appropriate antibodies for use as templates. Recently, new antibodies have been
      described that may fulfil this role, invigorating the field.

PMID- 21173881
TI  - Complementary roles of systems representing sensory evidence and systems
      detecting task difficulty during perceptual decision making.
AB  - Perceptual decision making is a multi-stage process where incoming sensory
      information is used to select one option from several alternatives. Researchers
      typically have adopted one of two conceptual frameworks to define the criteria
      for determining whether a brain region is involved in decision computations. One
      framework, building on single-unit recordings in monkeys, posits that activity in
      a region involved in decision making reflects the accumulation of evidence toward
      a decision threshold, thus showing the lowest level of BOLD signal during the
      hardest decisions. The other framework instead posits that activity in a decision
      making region reflects the difficulty of a decision, thus showing the highest
      level of BOLD signal during the hardest decisions. We had subjects perform a face
      detection task on degraded face images while we simultaneously recorded BOLD
      activity. We searched for brain regions where changes in BOLD activity during
      this task supported either of these frameworks by calculating the correlation of
      BOLD activity with reaction time - a measure of task difficulty. We found that
      the right supplementary eye field, right frontal eye field, and right inferior
      frontal gyrus had increased activity relative to baseline that positively
      correlated with reaction time, while the left superior frontal sulcus and left
      middle temporal gyrus had decreased activity relative to baseline that negatively
      correlated with reaction time. We propose that a simple mechanism that scales a
      region's activity based on task demands can explain our results.

PMID- 21173882
TI  - A pilot study differentiating recurrent major depression from bipolar disorder
      cycling on the depressive pole.
AB  - PURPOSE: A novel method for differentiating and treating bipolar disorder cycling
      on the depressive pole from patients who are suffering a major depressive episode
      is explored in this work. To confirm the diagnosis of type 1 or type 2 bipolar
      disorder, the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)
      criteria require that at least one manic or hypomanic episode be identified.
      History of one or more manic or hypomanic episodes may be impossible to obtain,
      representing a potential blind spot in the DSM-IV diagnostic criteria. Many
      bipolar patients who cycle primarily on the depressive side for many years carry
      a misdiagnosis of recurrent major depression, leading to treatment with
      antidepressants that achieve little or no relief of symptoms. This article
      discusses a novel approach for diagnosing and treating patients with bipolar
      disorder cycling on the depressive pole versus patients with recurrent major
      depression. PATIENTS AND METHODS: Patients involved in this study were formally
      diagnosed with recurrent major depression under DSM-IV criteria and had no
      medical history of mania or hypomania to support the diagnosis of bipolar
      disorder. All patients had suffered multiple depression treatment failures in the
      past, when evaluated under DSM-IV guidelines, secondary to administration of
      antidepressant drugs and/or serotonin with dopamine amino acid precursors.
      RESULTS: This study contained 1600 patients who were diagnosed with recurrent
      major depression under the DSM-IV criteria. All patients had no medical history
      of mania or hypomania. All patients experienced no relief of depression symptoms
      on level 3 amino acid dosing values of the amino acid precursor dosing protocol.
      Of 1600 patients studied, 117 (7.3%) nonresponder patients were identified who
      experienced no relief of depression symptoms when the serotonin and dopamine
      amino acid precursor dosing values were adjusted to establish urinary serotonin
      and urinary dopamine levels in the Phase III therapeutic ranges. All of the 117
      nonresponders who achieved no relief of depression symptoms were continued on
      this amino acid dosing value, and a mood-stabilizing drug was started. At this
      point, complete relief of depression symptoms, under evaluation with DSM-IV
      criteria, was noted in 114 patients within 1-5 days. With further dose adjustment
      of the mood-stabilizing drug, the remaining three nonresponders achieved relief
      of depression symptoms. CONCLUSION: Resolution of depression symptoms with the
      addition of a mood-stabilizing drug in combination with proper levels of
      serotonin and dopamine amino acid precursors was the basis for a clinical
      diagnosis of bipolar disorder cycling on the depressive pole.

PMID- 21173883
TI  - Walking impairment in patients with multiple sclerosis: exercise training as a
      treatment option.
AB  - Multiple sclerosis (MS) is a chronic disease of the central nervous system that
      culminates in the progression of physical and cognitive disability over time.
      Walking impairment is a ubiquitous feature of MS and a sentinel characteristic of
      the later or advanced stages of the disease. This paper presents a conceptual
      rationale along with empirical evidence for exercise training as a rehabilitation
      approach for managing walking impairment and improving walking function in
      persons with MS. Conceptually, MS is associated with a decrease in physical
      activity, which, in turn, can result in deconditioning across multiple domains of
      physiological functioning. The resulting deconditioning feeds back and further
      drives physical inactivity until a threshold is reached that likely initiates the
      progression of walking impairment in MS. Empirically, physical activity and
      exercise training have been associated with beneficial effects on walking
      function in persons with MS. This is based on cross-sectional, longitudinal, and
      experimental research that included diversity in the breadth of measures of
      walking, persons with MS, and exercise/physical activity characteristics. Of
      particular importance, future researchers might consider examining the
      combinatory effects of exercise training plus pharmacological agents on walking
      mobility in MS. Collectively, exercise training and physical activity might hold
      significant potential for the management of progressive mobility disability in
      MS.

PMID- 21173884
TI  - Neurocognitive impairment after off-pump and on-pump coronary artery bypass graft
      surgery - an Iranian experience.
AB  - BACKGROUND: Coronary artery bypass graft (CABG) surgery is one of the most
      commonly performed surgical procedures worldwide, and it may be accompanied by
      postoperative neurocognitive impairment. Although this complication has been
      attributed to the use of cardiopulmonary bypass, it is still a matter of debate
      whether the switch from on-pump to off-pump technique affects the cognitive
      function. OBJECTIVE: The aim of this study was to compare the impact of the on
      pump and off-pump techniques on neurocognitive impairment in low-risk CABG
      surgery groups. METHODS: In a descriptive and analytic study, 201 CABG patients
      with left-ventricular ejection fraction >30%, and without cardiac arrhythmia were
      enrolled. Before the elective operation, all patients underwent neurological
      examination and neurocognitive test, Mini-Mental State Examination (MMSE). Two
      months following the operation, both on- and off-pump, the patients were re
      examined by MMSE to detect any neurocognitive impairment. RESULTS: Out of 154
      patients included in the study, 95 (61.6%) and 59 (38.3%) patients were in off
      pump and on-pump groups, respectively. Mean age of the patients was 57.17 +/-
      9.82 years. A 2-month postoperative neurocognitive impairment was detected among
      17 patients of on-pump group (28.8%) and in 28 cases of off-pump group (29.4%) (P
      = 0.54). The mean postoperative MMSE scores were not comparable between groups
      (25.01 +/- 4.49 in off-pump group versus 23.73 +/- 4.88 in on-pump group, P =
      0.09). CONCLUSION: The present study revealed that in low-risk patients
      undergoing CABG surgery, either the techniques of on-pump or off-pump did not
      differ regarding the neurocognitive outcome 2 months after the procedure.

PMID- 21173885
TI  - Functional imaging of hippocampal dysfunction among persons with Alzheimer's
      disease: a proof-of-concept study.
AB  - Cholinergic deficits are an early and functionally significant manifestation of
      Alzheimer's disease (AD). These deficits contribute to impairment of
      hippocampally mediated information processing, including declarative memory
      impairments and abnormal auditory sensory gating. A functional imaging technique
      that facilitates identification of changes in cholinergically dependent
      hippocampal information processing would be of considerable use in the study and
      clinical evaluation of persons with this condition. Techniques that interrogate
      hippocampal function passively, ie, in a manner requiring no cognitive effort or
      novel task learning during the neuroimaging procedure, would also be especially
      useful in this cognitively impaired population. The functional magnetic resonance
      imaging sensory gating paradigm developed at the University of Colorado, CO, USA,
      is a functional neuroimaging technique that possesses both of these
      characteristics. We developed a demonstration project using this paradigm in
      which we passively interrogated hippocampal function in two subjects with
      probable AD of mild severity. Imaging data were quick and easy in these subjects
      and served usefully as an initial demonstration of the feasibility of using this
      neuroimaging method in this population. Preliminary analyses of the data obtained
      from these subjects identified abnormal blood oxygen level-dependent responses
      when compared with four healthy comparators, and the pattern of these responses
      was consistent with impaired function of the auditory sensory gating network. The
      strengths and limitations of this neuroimaging paradigm and the additional issues
      that require investigation in order to continue its development into a research
      and clinical technique for use in this population are discussed.

PMID- 21173886
TI  - Microfluidic on-chip fluorescence-activated interface control system.
AB  - A microfluidic dynamic fluorescence-activated interface control system was
      developed for lab-on-a-chip applications. The system consists of a straight
      rectangular microchannel, a fluorescence excitation source, a detection sensor, a
      signal conversion circuit, and a high-voltage feedback system. Aqueous NaCl as
      conducting fluid and aqueous glycerol as nonconducting fluid were introduced to
      flow side by side into the straight rectangular microchannel. Fluorescent dye was
      added to the aqueous NaCl to work as a signal representing the interface
      position. Automatic control of the liquid interface was achieved by controlling
      the electroosmotic effect that exists only in the conducting fluid using a high
      voltage feedback system. A LABVIEW program was developed to control the output of
      high-voltage power supply according the actual interface position, and then the
      interface position is modified as the output of high-voltage power supply. At
      last, the interface can be moved to the desired position automatically using this
      feedback system. The results show that the system presented in this paper can
      control an arbitrary interface location in real time. The effects of viscosity
      ratio, flow rates, and polarity of electric field were discussed. This technique
      can be extended to switch the sample flow and droplets automatically.

PMID- 21173888
TI  - Renal Transplantation in the Presence of a Positive Cytotoxic Antibody.

PMID- 21173889
TI  - The first baboon-to-human transplants.

PMID- 21173890
TI  - The challenge of acute non-compressive transverse myelopathies.

PMID- 21173891
TI  - Carotid endarterectomy vs. carotid stenting: fairly comparable or unfairly
      compared?

PMID- 21173892
TI  - Paradoxical sleep suppresses immediate early gene expression in the rodent
      suprachiasmatic nuclei.
AB  - Light stimulates neuronal activity with subsequent expression of the protein
      product of the immediate early gene, c-fos, in the Suprachiasmatic Nuclei (SCN).
      Non-photic stimuli is also thought to modulate activity within the SCN. Here, we
      sought to determine the effects intrinsic stimuli, specifically, the states of
      sleep upon c-fos protein expression in the SCN. In 16 rats, c-fos protein
      expression was evaluated at a fixed time of 1600 h (subjective night), following
      1 h of electroencephalographically defined sleep. During sleep, as the state of
      paradoxical sleep (PS) increased, c-fos protein expression decreased (r = -0.41,
      p < 0.033). The PS-associated reduction of c-fos positive cells occurred equally
      between animals asleep in the light and those asleep in the dark. We propose a
      model whereby PS duration might function as a homeostatic-entraining mechanism to
      reduce neuronal activity within the SCN, and thereby modulate circadian rhythms
      during sleep.

PMID- 21173894
TI  - Sleep complaints affecting school performance at different educational levels.
AB  - The clear association between reports of sleep disturbance and poor school
      performance has been documented for sleepy adolescents. This study extends that
      research to students outside the adolescent age grouping in an associated school
      setting (98 middle school students, 67 high school students, and 64 college
      students). Reported restless legs and periodic limb movements are significantly
      associated with lower GPA's in junior high students. Consistent with previous
      studies, daytime sleepiness was the sleep variable most likely to negatively
      affects high school students. Sleep onset and maintenance insomnia were the
      reported sleep variables significantly correlated with poorer school performance
      in college students. This study indicates that different sleep disorder variables
      negatively affect performance at different age and educational levels.

PMID- 21173893
TI  - Perspective on sleep and aging.
AB  - There is a strong body of data directly interrelating sleep problems with mood
      disorders. There is a growing data base directly associating sleep disorders with
      attention and memory problems. Motor disorders, especially involving the
      dopaminergic system, may produce sleep problems, including a possible association
      between disordered sleep and nocturnal falls. Sleep disorders may be causal
      conditions for metabolic diseases and increased risk for morbidity and mortality.
      Sleep and health are directly interrelated. To further probe these issues,
      especially as related to the aging process, investigators need to utilize tools
      and concepts from genomics and epigenetics, proteomics, metabolomics, any future
      ...omics, molecular neuroimaging, and cognitive neuroscience.

PMID- 21173895
TI  - Weak and straddling secondary nicotinic synapses can drive firing in rat
      sympathetic neurons and thereby contribute to ganglionic amplification.
AB  - Interactions between nicotinic excitatory postsynaptic potentials (EPSPs)
      critically determine whether paravertebral sympathetic ganglia behave as simple
      synaptic relays or as integrative centers that amplify preganglionic activity.
      Synaptic connectivity in this system is characterized by an n + 1 pattern of
      convergence, where each ganglion cell receives one very strong primary input and
      a variable number (n) of weak secondary inputs that are subthreshold in strength.
      To test whether pairs of secondary nicotinic EPSPs can summate to fire action
      potentials (APs) and thus mediate ganglionic gain in the rat superior cervical
      ganglion, we recorded intracellularly at 34 degrees C and used graded presynaptic
      stimulation to isolate individual secondary synapses. Weak EPSPs in 40 of 53
      neurons had amplitudes of 0.5-7 mV (mean 3.5 +/- 0.3 mV). EPSPs evoked by paired
      pulse stimulation were either depressing (n = 10), facilitating (n = 9), or
      borderline (n = 10). In 15 of 29 cells, pairs of weak secondary EPSPs initiated
      spikes when elicited within a temporal window <20 ms, irrespective of EPSP
      amplitude or paired pulse response type. In six other neurons, we observed novel
      secondary EPSPs that were strong enough to straddle spike threshold without
      summation. At stimulus rates <1 Hz straddling EPSPs appeared suprathreshold in
      strength. However, their limited ability to drive firing could be blocked by the
      afterhyperpolarization following an AP. When viewed in a computational context,
      these findings support the concept that weak and straddling secondary nicotinic
      synapses enable mammalian sympathetic ganglia to behave as use-dependent
      amplifiers of preganglionic activity.

PMID- 21173896
TI  - Interfacing sleep and aging.

PMID- 21173897
TI  - Modulation of memory by vestibular lesions and galvanic vestibular stimulation.
AB  - For decades it has been speculated that there is a close association between the
      vestibular system and spatial memories constructed by areas of the brain such as
      the hippocampus. While many animal studies have been conducted which support this
      relationship, only in the last 10 years have detailed quantitative studies been
      carried out in patients with vestibular disorders. The majority of these studies
      suggest that complete bilateral vestibular loss results in spatial memory
      deficits that are not simply due to vestibular reflex dysfunction, while the
      effects of unilateral vestibular damage are more complex and subtle. Very
      recently, reports have emerged that sub-threshold, noisy galvanic vestibular
      stimulation can enhance memory in humans, although this has not been investigated
      for spatial memory as yet. These studies add to the increasing evidence that
      suggests a connection between vestibular sensory information and memory in
      humans.

PMID- 21173898
TI  - Hormone replacement after thyroid and parathyroid surgery.
AB  - BACKGROUND: Hypothyroidism and hypocalcemia are common after thyroid and
      parathyroid surgery. In this article, the authors provide clinically-oriented
      recommendations to help surgeons, general practitioners, internists, and
      endocrinologists give their affected patients adequate hormone replacement
      therapy. METHODS: Selective evaluation of original articles and reviews that were
      retrieved by a PubMed search over the years 1980 to 2010, as well as of the
      recommendations of medical societies including the Endocrine Society (USA), the
      German Society for Endocrinology (Deutsche Gesellschaft fur Endokrinologie), and
      the American and European Thyroid Associations. RESULTS: Important issues in L
      thyroxine replacement therapy include: the selection of the hormone preparation
      (T4 or T4/T3), combination with iodine (yes/no), the definition of therapeutic
      TSH ranges (particularly after surgery for thyroid cancer), the extent of
      remaining thyroid tissue after goiter surgery and its significance, underlying
      diseases, and drug interactions. The major issues in the treatment of
      postoperative hypoparathyroidism are: the selection of suitable calcium and
      vitamin D preparations, the definition of therapeutic goals, the treatment of
      hypercalciuria and hyperphosphatemia, and the option of recombinant parathormone
      therapy. CONCLUSION: Effective treatment requires an appropriate choice of
      medication and an understanding of its pharmacokinetics as well as of the
      possible effects of the patient's underlying disease, comorbidities, and other
      medications on its absorption and metabolism.

PMID- 21173900
TI  - Fractured neck of femur--internal fixation versus arthroplasty. Additional
      information needed.

PMID- 21173899
TI  - Boxing-acute complications and late sequelae: from concussion to dementia.
AB  - BACKGROUND: Boxing has received increased public attention and acceptance in
      recent years. However, this development has not been accompanied by a critical
      discussion of the early and late health complications. METHODS: We selectively
      review recent studies on the acute, subacute, and chronic neuropsychiatric
      consequences of boxing. RESULTS: Cerebral concussions ("knock-outs") are the most
      relevant acute consequence of boxing. The number of reported cases of death in
      the ring seems to have mildly decreased. Subacute neuropsychological deficits
      appear to last longer than subjective symptoms. The associated molecular changes
      demonstrate neuronal and glial injury correlated with the number and severity of
      blows to the head (altered total tau, beta-amyloid, neurofilament light protein,
      glial fibrillary acidic protein, and neuron-specific enolase). The risk of a
      punch-drunk syndrome (boxer's dementia, dementia pugilistica) as a late effect of
      chronic traumatic brain injury is associated with the duration of a boxer's
      career and with his earlier stamina. There are similarities (e.g. increased risk
      with ApoE4-polymorphism, beta-amyloid pathology) and differences (more tau
      pathology in boxers) compared with Alzheimer's disease. CONCLUSION: Protective
      gear has led to a remarkable reduction of risks in amateur boxing. Similar
      measures can also be used in professional boxing, but may decrease the thrill,
      which does appeal to many supporters.

PMID- 21173901
TI  - Short periods of observation.

PMID- 21173902
TI  - Local estriol treatment.

PMID- 21173904
TI  - Dietary salt is a health political problem.

PMID- 21173906
TI  - Unacceptable pain.

PMID- 21173907
TI  - A new treatment strategy for acute liver failure.
AB  - Acute liver failure (ALF) is a syndrome defined by coagulopathy and
      encephalopathy and no effective treatments have been established, except for
      liver transplantation. However, considering the limited supply of donors, we
      should endeavor to prevent the progression of this syndrome in its early stage to
      improve the prognosis of patients with ALF. Recently, several authors have
      reported that over-activation of intrahepatic macrophages plays an important role
      in the progression of ALF and we have developed a new treatment method,
      transcatheter arterial steroid injection therapy (TASIT), to suppress macrophage
      activation. We have now used TASIT for 5 years and have found that TASIT is
      effective for patients with over-activation of macrophages in the liver but not
      for those with lesser activation of macrophages. Therefore, to identify the most
      appropriate patients for TASIT, we tried to categorize patients with ALF or acute
      liver injury according to markers for the degree of intrahepatic macrophage
      activation. This approach was helpful to select the appropriate treatment
      including liver transplantation. We believe that it is essential to analyze
      disease progression in each patient before selecting the most appropriate
      treatment.

PMID- 21173908
TI  - Clinical characteristics of null responders to Peg-IFNalpha2b/ribavirin therapy
      for chronic hepatitis C.
AB  - AIM: To predict which chronic hepatitis C patients are likely to be late
      responders, we herein investigated the clinical characteristics of null
      responders at 36 wk with hepatitis C virus (HCV) genotype Ib and a high viral
      load during the course of pegylated interferon (Peg-IFN)/ribavirin therapy.
      METHODS: One hundred forty-two patients with genotype Ib HCV and a high viral
      load were included in this study. Peg-IFNalpha2b (1.5 MUg/kg once a week) and
      ribavirin (600-1000 mg per day according to body weight) were administered for 48
      wk. We defined null-responders as the cases that never cleared serum HCV RNA as
      determined using RT-PCR until 36 wk. Other patients were defined as responders.
      We compared the clinical characteristics (age, gender, body mass index, previous
      treatment) and HCV RNA titer during the therapy between null-responders and
      responders. RESULTS: The HCV RNA clearance rate was 17.9% (24/134), 46.3%
      (62/134), 60.6% (86/142), 86.6% (123/142), and 88.0% (125/142) at 4, 8, 12, 24,
      and 36 wk, respectively. There were 17 patients (12.0%) who were still null
      responders at 36 wk. There were no differences in the clinical characteristics
      between the responders and null-responders except for the titer and decline rates
      of HCV RNA at 1 wk and 4 wk. The HCV RNA titers at 1 wk and after 4 wk of
      treatment were significantly higher in the null-responders in comparison to the
      responders (P <0.01). The serum HCV RNA titers of the responders decreased by 1.3
      log after 1 wk of treatment, and 1.6 log after 4 wk of treatment, respectively.
      On the other hand, the titers of the null responders decreased by only 0.5 log
      after 1 wk, and 0.7 log after 4 wk of treatment, respectively. The decrease rates
      of HCV RNA after 1 and 4 wk of treatment were significantly worse for null
      responders than for the responders (P <0.01). CONCLUSION: The HCV RNA titer at 1
      wk and 4 wk after initiating treatment may be useful for predicting null
      responders to Peg-IFNalpha2b/ribavirin therapy. However, further investigation is
      needed to determine the optimal time at which the decision to discontinue the Peg
      IFNalpha2b/ribavirin therapy for null-responders can be made.

PMID- 21173909
TI  - Hepatic portal venous gas due to cryptosporidiosis in a patient with acquired
      immunodeficiency syndrome.
AB  - Although the presence of hepatic portal venous gas (HPVG) on computed tomography
      (CT) is typically an ominous finding, HPVG may sometimes be less catastrophic.
      The clinical significance of HPVG is variable, and it depends primarily on the
      underlying pathology. We report a case of a patient with acquired
      immunodeficiency syndrome (AIDS) who was found to have HPVG on CT as a presumed
      result of gastrointestinal cryptosporidiosis, an association that, to our
      knowledge, has not been reported. This case illustrates another cause of HPVG
      that should be considered in patients with AIDS.

PMID- 21173910
TI  - Acute liver injury induced by weight-loss herbal supplements.
AB  - We report three cases of patients with acute liver injury induced by weight-loss
      herbal supplements. One patient took Hydroxycut while the other two took
      Herbalife supplements. Liver biopsies for all patients demonstrated findings
      consistent with drug-induced acute liver injury. To our knowledge, we are the
      first institute to report acute liver injury from both of these two types of
      weight-loss herbal supplements together as a case series. The series emphasizes
      the importance of taking a cautious approach when consuming herbal supplements
      for the purpose of weight loss.

PMID- 21173911
TI  - Hepatocellular carcinoma, with portal thrombus after viral eradication,
      disappeared by 5-fluorouracil and interferon.
AB  - Hepatocarcinogenesis after a sustained virological response (SVR) in type C
      chronic hepatitis and cirrhosis is an important issue in endemic areas;
      hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) therapy is
      especially very hard. We herein report a first case in which combination therapy
      with interferon-alpha and continuous intra-arterial infusion of 5-fluorouracil
      (designated as FAIT) provided a complete response in HCC with PVTT after SVR.
      Therefore, we think that FAIT is a good option to treat HCC with or without PVTT,
      even after SVR.

PMID- 21173913
TI  - Staining for p53 and Ki-67 increases the sensitivity of EUS-FNA to detect
      pancreatic malignancy.
AB  - AIM: To investigate whether tumor marker staining can improve the sensitivity of
      endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) to diagnose
      pancreatic malignancy. METHODS: Patients who underwent EUS-FNA were
      retrospectively identified. Each EUS-FNA specimen was evaluated by routine
      cytology and stained for tumor markers p53, Ki-67, carcinoembryonic antigen (CEA)
      and CA19-9. Sensitivity, specificity, positive and negative predictive values
      (PPV and NPV), and positive and negative likelihood ratios (PLR and NLR) were
      calculated in order to evaluate the performance of each test to detect
      malignancy. RESULTS: Sixty-one specimens had complete sets of stains, yielding 49
      and 12 specimens from pancreatic adenocarcinomas and benign pancreatic lesions
      due to pancreatitis, respectively. Cytology alone had sensitivity and specificity
      of 41% and 100% to detect malignancy, respectively. In 46% of the specimens,
      routine cytology alone was deemed indeterminate. The addition of either p53 or Ki
      67 increased the sensitivity to 51% and 53%, respectively, with perfect
      specificity, PPV and PLR (100%, 100% and infinite). Both stains in combination
      increased the sensitivity to 57%. While additional staining with CEA and CA19-9
      further increased the sensitivity to 86%, the specificity, PPV and PLR were
      significantly reduced (at minimum 42%, 84% and 1, respectively). Markers in all
      combinations performed poorly as a negative test (NPV 26% to 47%, and NLR 0.27
      and 0.70). CONCLUSION: Immunohistochemical staining for p53 and Ki-67 can improve
      the sensitivity of EUS-FNA to diagnose pancreatic adenocarcinoma.

PMID- 21173914
TI  - Small bowel parasitosis as cause of obscure gastrointestinal bleeding diagnosed
      by capsule endoscopy.
AB  - Hookworm infection is a relatively common cause of anemia in endemic areas.
      However, it is rarely encountered in Europe. In this report we describe the case
      of a 24-year old patient originating from an endemic area who was admitted due to
      severe anemia, with an Hct of 15.6% and eosinophilia (Eosinophils: 22.4%). While
      both esophagogastroduodenoscopy and colonoscopy were non-diagnostic, capsule
      endoscopy revealed a large number of hookworms infesting his small bowel and
      withdrawing blood. The patient was successfully treated with Albendazole. Capsule
      endoscopy was proven an important tool in diagnosing intestinal parasitosis.

PMID- 21173912
TI  - Photodynamic therapy: Palliation and endoscopic technique in cholangiocarcinoma.
AB  - Cholangiocarcinoma is the primary malignancy arising from the biliary epithelium.
      The disease is marked by jaundice, cholestasis, and cholangitis. Over 50 percent
      of patients present with advanced stage disease, precluding curative surgical
      resection as an option of treatment. Prognosis is poor, and survival has been
      limited even after biliary decompression. Palliative management has become the
      standard of care for unresectable disease and has evolved to include an
      endoscopic approach. Photodynamic therapy (PDT) consists of administration of a
      photosensitizer followed by local irradiation with laser therapy. Several studies
      conducted in Europe and the United States have shown a marked improvement in the
      symptoms of cholestasis, survival, and quality of life. This article summarizes
      the published experience regarding PDT for cholangiocarcinoma and the steps
      required to administer this therapy safely.

PMID- 21173915
TI  - Endoscopic extraction of a metal key impacted within the appendix.
AB  - Ingested foreign bodies are rarely impacted in the appendix. They may be
      clinically latent or cause complications such as appendicitis or intestinal
      perforation, thus requiring prompt and appropriate therapy. A case is reported of
      a psychiatric, but in other respects asymptomatic, patient who presented with an
      ingested metal key deeply impacted within the appendix. The patient underwent
      urgent coloscopy for retrieval. Initially all conventional endoscopic instruments
      proved ineffective and the key was finally extracted using a simple manoeuvre,
      described herein.

PMID- 21173916
TI  - Placement of a fully covered self-expandable metal stent in a young patient with
      chronic pancreatitis.
AB  - Plastic stent insertion is a treatment option for pancreatic duct stricture with
      chronic pancreatitis. However, recurrent stricture is a limitation after removing
      the plastic stent. Self-expandable metal stents have long diameters and patency.
      A metal stent has become an established management option for pancreatic duct
      stricture caused by malignancy but its use in benign stricture is still
      controversial. We introduce a young patient who had chronic pancreatitis and
      underwent several plastic stent insertions due to recurrent pancreatic duct
      stricture. His symptoms improved after using a fully covered self-expandable
      metal covered stent and there was no recurrence found at follow-up at the
      outpatient department.

PMID- 21173917
TI  - Cytomegalovirus gastritis.
AB  - Cytomegalovirus (CMV) has been increasingly recognized as an important common
      pathogen in an immunocompromised state. The colon and stomach are the most common
      sites of its gastrointestinal infection. Symptoms of CMV gastritis are usually
      nonspecific and include epigastric pain, fever, nausea and bleeding. Endoscopic
      features are quite variable and include macroscopically normal mucosa, diffuse
      erythema, nodules, pseudotumors, erosions and ulcers. The bioptic detection of
      intranuclear inclusions is the hallmark of CMV infection. Most gastrointestinal
      CMV infection responds well to ganciclovir. We present endoscopic and
      histopathological features of CMV gastritis in a 71 year old woman receiving long
      term prednisolone for pemphigus vulgaris.

PMID- 21173918
TI  - An Adolescent Patient with Scabies Mimicking Gottron Papules.
AB  - Atypical features of scabies occur in infants and children and patients with
      prolonged use of corticosteroids or immunosuppression. We report a non
      immunosuppressed 15-year-old female case of scabies showing scaly reddish papules
      over the proximal interphalangeal joints mimicking Gottron papules in classic
      dermatomyositis. Periungal erythema was also seen. Four months' topical
      corticosteroids from previous clinics had been used. Dermoscopic findings were
      consistent with typical pictures of scabies. Scraping of hand crusts demonstrated
      scabies mites and ova. Skin lesions of the patient were cured with oral
      ivermectin and topical 10% crotamiton. This case suggests that a lesion
      resembling Gottron papules may be added to the panel of unusual presentations of
      scabies.

PMID- 21173919
TI  - Ectopic Cutaneous Schistosomiasis mansoni in the Sacral Region.
AB  - The authors report one case of late cutaneous Schistosomiasis mansoni in a biopsy
      of a skin lesion in the sacral region in a 51-year-old female living in Contagem,
      Minas Gerais. The patient was treated successfully with oxamniquine (Mansil(r)).

PMID- 21173920
TI  - Strict Anatomical Colocalization of Vitiligo and Elastolytic Granulomas.
AB  - Vitiligo is the most common depigmenting disorder, with a worldwide occurrence of
      0.1-2% in the general population. Multiple conditions have been described
      colocalized in vitiligo patches, like psoriasis or lichen planus. However,
      actinic granuloma has not been described in association with vitiligo lesions so
      far.

PMID- 21173921
TI  - Genital Infection as a First Sign of Acute Myeloid Leukemia.
AB  - Fournier's gangrene is a life-threatening disorder caused by aerobic and
      anaerobic bacterial infection. We report a case of genital infection as the
      initial warning sign of acute myeloid leukemia. We were able to prevent
      progression to Fournier's gangrene in our patient by immediate intensive therapy
      with incision, blood transfusions and intravenous administration of antibiotics.
      This case suggests that hematologists and dermatologists should keep in mind that
      genital infection can be a first sign of hematologic malignancy.

PMID- 21173922
TI  - Intravascular Papillary Endothelial Hyperplasia (Masson's Tumor) of the Mouth - A
      Case Report.
AB  - We report a rare case of intravascular papillary endothelial hyperplasia (IPEH)
      of the oral mucosa. This neoplasm, known as Masson's tumor, is an unusual
      vascular lesion of proliferating endothelial cells. It is usually confined to the
      lumen of preexisting vessels or vascular malformations. The principal
      significance of IPEH is its microscopic resemblance to angiosarcoma and possible
      misdiagnosis as such. Achieving a correct diagnosis is essential to avoid
      subjecting a patient to unnecessarily aggressive therapy. For this reason,
      awareness of this lesion is very important for dermatologists and dentists. In
      this article, we discuss the clinical features, histopathological
      characteristics, and management of IPEH and review the pertinent literature.

PMID- 21173923
TI  - Alopecia Areata Associated with Localized Vitiligo.
AB  - Alopecia areata is a common cause of noncicatricial alopecia that occurs in a
      patchy, confluent or diffuse pattern. It may occur as a single, self-limiting
      episode or may recur at varying intervals over many years. The association of
      alopecia areata with localized vitiligo has not been reported. The association of
      alopecia areata with localized vitiligo in the same patient is documented here;
      it is the first of its kind.

PMID- 21173924
TI  - De novo Renal Transplantation after Kaposi Sarcoma: Favorable Outcome in a
      Patient Receiving Sirolimus and Mycophenolate-Based Immunosuppression.
AB  - Immunosuppressive treatment increases the risk of infection and malignancy in
      organ transplant recipients. We report on a 42-year-old male renal transplant
      recipient who lost his first graft after reduction of immunosuppressive treatment
      due to Kaposi sarcoma and who successfully underwent a second renal transplant 10
      years later. The patient's current treatment consists of low-dose prednisone, and
      the two antiproliferative immunosuppressants mycophenolate mofetil and rapamycin.
      4.5 years after his second transplant, the serum creatinine is 1 mg/dl and the
      patient has no signs of recurrent disease.

PMID- 21173925
TI  - Photoallergic Contact Dermatitis due to Ketoprofen and Hydrogenated Rosin
      Glycerol Ester.
AB  - A topical application of a nonsteroidal anti-inflammatory drug (NSAID) may induct
      an adverse reaction of photoallergic contact dermatitis. The occlusive usage may
      provoke concomitant photoallergic sensitizations to an NSAID and other
      ingredients. We describe a 58-year-old woman with photoallergic contact
      dermatitis from ketoprofen and hydrogenated rosin glycerol ester in the applied
      compress. Our case indicates that photopatch testing with all ingredients is
      required to verify the actual photoallergen(s).

PMID- 21173926
TI  - Frontal Fibrosing Alopecia: Role of Dermoscopy in Differential Diagnosis.
AB  - Frontal fibrosing alopecia (FFA) is more common in postmenopausal women, but it
      can occur in younger women. Some authors consider FFA to be a distinct frontal
      variant of lichen planopilaris. From a clinical point of view, this relatively
      uncommon condition is characterized by progressive frontotemporal recession due
      to inflammatory destruction of hair follicles. Dermoscopy can be very useful, as
      the differential diagnosis between traction alopecia, alopecia areata, FFA and
      cicatricial marginal alopecia may be difficult. It is not clear whether or not
      treatment alters the natural history of the disease - the disease stabilized with
      time in most of the patients with or without continuing treatment. Here we report
      a case of a 50-year-old woman with FFA and discuss the relevance of dermoscopy in
      the differential diagnosis of this disease.

PMID- 21173927
TI  - Successful Treatment of Anogenital Wart with a Topical Vitamin D(3) Derivative in
      an Infant.
AB  - Anogenital warts are an infectious disorder of the anogenital lesion caused by
      one or more human papilloma viruses. Verruca is commonly treated with freezing
      with liquid nitrogen, laser therapy or application of imiquimod. Such ablative
      treatment may cause pain and scars on the anogenital lesion. We herein report an
      infant case of anogenital wart which was successfully treated with a topical
      vitamin D(3) derivative. Topical application of a vitamin D(3) derivative may be
      an alternative therapy for anogenital warts in infants.

PMID- 21173928
TI  - Allergic Contact Dermatitis with Diffuse Erythematous Reaction from
      Diisopropanolamine in a Compress.
AB  - Compresses containing a nonsteroidal antiinflammatory drug (NSAID) are commonly
      used in Japan. However, this treatment may induce both allergic and photoallergic
      contact dermatitis from the NSAIDs and their ingredients. Here, we describe a
      case of allergic contact dermatitis with diffuse erythematous reaction due to
      diisopropanolamine in the applied compress. The absorption of diisopropanolamine
      might have been enhanced by the occlusive condition.

PMID- 21173929
TI  - Lichen Sclerosus et Atrophicus with Cutaneous Distribution Simulating Lichen
      Planus.
AB  - Lichen sclerosus (LS) et atrophicus is a disease of unknown etiology, although
      hereditary, endocrine, and autoimmune factors are known to be involved. While the
      anal and genital regions are predominantly affected, only 2.5% of patients
      present with extragenital lesions, particularly of the trunk, neck, and upper
      limbs. The possible relationship between lichen sclerosus et atrophicus and both
      lichen planus (LP) and localized scleroderma (morphea) has not been clearly
      established, although in a number of cases, several of these conditions have been
      found simultaneously. We report the case of a 31-year-old woman with LS lesions
      affecting the neck, upper back, wrist and dorsum of the feet. The unusual
      character of this presentation is pointed out, along with its clinical similarity
      to LP.

PMID- 21173930
TI  - Skin Detachment and Regrowth in Toxic Epidermal Necrolysis.
AB  - Toxic epidermal necrolysis is a rare but clinically well-described dermatological
      pathology. However, clinical pictures of this disorder in text books do not
      reflect its dynamic evolution. Usually, the desquamative post-bullous stage is
      represented, neglecting the initial bullous stage as well as the skin healing.
      With one clinical case, we provide a day-after-day illustration of the evolution
      of a patient suffering from toxic epidermal necrolysis. During one month, a skin
      area of a limb was regularly photo-documented.

PMID- 21173931
TI  - Influenza vaccination coverage in the 2004/05, 2005/06, and 2006/07 seasons: a
      secondary data analysis based on billing data of the German associations of
      statutory health insurance physicians.
AB  - BACKGROUND: The German Standing Committee on Vaccination recommends annual
      vaccination for persons in high-risk groups in order to lower the disease burden
      associated with seasonal influenza. The stated target is 75% vaccination coverage
      of people over age 60 by the year 2010. We present statistics based on billing
      data of the German associations of statutory health insurance physicians
      regarding vaccination coverage for influenza in the three seasons from 2004/05 to
      2006/07. METHODS: We analyzed anonymous data from 14 of the 17 associations of
      statutory health insurance physicians in Germany. The study population consisted
      of all persons covered by statutory health insurance in the geographical areas
      under study (61.5 million persons, or 86% of the total population of these
      areas). Vaccination coverage was calculated as the number of vaccinated persons
      divided by the number of persons covered by statutory health insurance. RESULTS:
      The influenza vaccination coverage of the overall study population was 19% in
      2004/05, 22% in 2005/06, and 21% in 2006/07. The coverage of persons over age 60
      was 45% in 2004/05, 50% in 2005/06, and 49% in 2006/07 and was higher in areas
      that were formerly part of East Germany than in the rest of the country. More
      than a third of all vaccinated persons were vaccinated in all three seasons, as
      were almost half of the vaccinated persons over age 60. CONCLUSION: There was no
      secular increase in influenza vaccination coverage over the period 2005/06 to
      2006/07. The stated target of 75% vaccination coverage for persons over age 60 by
      the year 2010 would thus seem to represent a major challenge for all persons
      involved. The analysis of data of the associations of statutory health insurance
      physicians enables continuous monitoring of influenza vaccination coverage.

PMID- 21173932
TI  - Cerebral angiopathies as a cause of ischemic stroke in children: differential
      diagnosis and treatment options.
AB  - BACKGROUND: Ischemic stroke in children can present with an epileptic seizure or
      be initially asymptomatic. The median time to diagnosis is 24 hours. METHODS:
      This review is based on a selective literature search, with additional
      consideration of published guidelines and the authors' personal experience.
      RESULTS: In Europe and the USA, the combined incidence of ischemic and
      hemorrhagic stroke in childhood is 2.5 to 10 per 100 000 children per year. 40%
      of ischemic strokes in childhood occur after an infectious illness or in
      association with a congenital heart defect, sickle-cell anemia, or a
      coagulopathy. Arterial dissection and chronic, progressive cerebral
      arteriopathies, particularly moyamoya disease, each account for up to 10% of
      childhood strokes. Magnetic resonance imaging can be used to demonstrate infarcts
      and to display the perfusion of ischemic areas and the surrounding brain tissue;
      arterial and venous occlusions can be defined more precisely. Children with
      arterial dissection, vasculitis, and para-infectious cerebral ischemia should be
      treated empirically, with medications and supportive care, according to the
      treatment plans developed for adults. For patients with moyamoya disease,
      surgical revascularization with extra-intracranial bypass techniques is
      recommended. DISCUSSION: The current data provide an inadequate evidence base for
      the treatment of stroke in children. Potential revascularization or thrombolysis
      must be discussed individually in each case. For the treatment of temporary, para
      infectious cerebral ischemia, hemodynamic optimization is an available option.
      Better evidence is needed regarding the surgical treatment of moyamoya disease.

PMID- 21173934
TI  - Continuous medical education in ultrasonography.

PMID- 21173933
TI  - The prenatal diagnosis of genetic diseases.
AB  - BACKGROUND: Prenatal diagnosis is a subfield of clinical genetics and gynecology
      that exemplifies the effective integration of theoretical and clinical medicine.
      Milestones in its history include the development of cytogenetic, molecular
      genetic, and molecular cytogenetic methods as well as advances in
      ultrasonography. The latter technique not only improves the safety of invasive
      procedures, but also enables earlier and more reliable diagnosis of congenital
      malformations. METHODS: This article provides an overview of the subject in the
      light of selectively reviewed literature, guidelines, and recommendations.
      RESULTS AND CONCLUSION: Invasive prenatal diagnosis is most commonly performed to
      assess the embryonal/fetal chromosome set. An increasing number of monogenic
      diseases can be diagnosed prenatally by either genetic or biochemical testing,
      depending on the particular disease being sought. Polygenic and multifactorial
      diseases cannot be reliably diagnosed by genetic testing at present, although a
      number of malformations can be ascertained prenatally by ultrasonography. We
      discuss the applications and limitations of invasive and noninvasive techniques
      for prenatal diagnosis.

PMID- 21173935
TI  - The role of Power Doppler ultrasonography in comparison with biological markers
      in the evaluation of disease activity in Juvenile Idiopathic Arthritis.
AB  - OBJECTIVE: To evaluate the performance of Power Doppler Ultrasonography (PDUS)
      compared with biological markers, in the assessment of disease activity in
      children with Juvenile Idiopathic Arthritis (JIA). METHODS: Forty hospital visits
      were studied comprising 32 patients with JIA, during one year of follow-up. Each
      patient underwent clinical, laboratory and ultrasound (PDUS) evaluation. The
      physician global assessment score on the visual analog scale (PhGA) was used as a
      standard for assessing disease activity, based on previous studies. The PDUS
      signal was scored according to a semiquantitative four grade scale (0-3).
      RESULTS: PDUS assessment of synovial vascularisation was more sensitive than
      erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) in
      identification of the active disease: 90.4% vs. 57% and 28.5% respectively. CRP
      had a higher specificity (94%) in comparison with PDUS (89.5%). A significant
      association between clinical examination (PhGA) and PDUS score or ESR was found.
      Kappa statistics revealed a high level of agreement between PhGA and PDUS score
      (k=0.799) and a low level of agreement between PhGA and biological markers
      (k=0.356 and k=0.225 respectively). Patients with higher PDUS score (>or=2),
      ESR>or=30 mm/h or CRP>or=2 mg/dl were more likely to have active disease.
      CONCLUSION: Laboratory tests used today are not sufficiently sensitive for the
      prediction of active disease. PDUS assessment of synovial vascularisation is a
      technique with good sensitivity and specificity, thus it may be a beneficial
      criteria for evaluating disease activity in JIA, completing conventional clinical
      examination.

PMID- 21173936
TI  - Ultrasonographic aspect of subcutaneous tissue dystrophies as a result of insulin
      injections.
AB  - AIMS: The aim of the study was to evaluate by ultrasonography the local
      dystrophies caused by insulin subcutaneous injections. The insulin treated
      diabetic patients must inject their long life insulin into normal tissue. The
      objective was to add ultrasonographic arguments to the clinic examination in
      order to periodically reconsider the available area to be used. PATIENTS AND
      METHODS: Forty insulin treated patients (14 male, 26 female) were clinically
      diagnosed with hypertrophic, atrophic, nodular, or inflammatory-like tissue
      dystrophies as a consequence of injections. These local dystrophies are not
      always conspicuous, barely suggesting a subdermal pathology. US evaluation,
      mainly subcutis, was used for assessing them. RESULTS: Besides the clinical
      signs, ultrasonography offers some distinct appearances: a simple subcutis
      hypertrophy, a variety of nodular-shaped or diffuse hyperechogenity, subcutis
      atrophy, complex multilayer changes or possible inflammatory reactions. These
      abnormal entities have led to erratic insulin absorption and glucose control
      deterioration, if the patients have continued to inject into the same areas.
      CONCLUSIONS: Ultrasound interrogation should be used as a non-invasive measure
      for diagnosing insulin injections local dystrophies. Once diagnosed, their future
      evolution should be observed. By making a real ultrasonographic map of the
      injected areas a functional insulin treatment could be obtained and preserved.

PMID- 21173937
TI  - Fetal Doppler ultrasound assessment of ductus venosus in a 31-40 [corrected]
      weeks gestation normal fetus in the Pakistani population.
AB  - OBJECTIVE: To evaluate the ductus venosus hemodynamic parameters in 31-40 weeks
      gestation normal fetus in the Pakistani population using Doppler ultrasonography.
      MATERIAL AND METHODS: In a standardized protocol 106 pregnant women (31 to 40
      gestation weeks) were scanned. The peak systolic velocity (maximum velocity
      during S wave) (PSV), peak velocity index (peak velocity S wave minus peak
      velocity A wave/peak velocity D wave) (PVI), and S/A ratio (peak velocity S
      wave/peak velocity A wave) were measured. RESULTS: Out of 106 patients, 100
      patients were successfully scanned (94% success rate). In the 31-35 weeks
      gestational age group the mean PSV was 59.7 cm/s, PI 0.7, and S/A 2.16. In the 36
      40 weeks gestational age group the mean PSV was 72.9 cm/s, PI 0.42, and S/A 2.46.
      CONCLUSIONS: As the normal pregnancy advances the PSV, the flow resistance and
      S/A ratio in ductus venosus increase.

PMID- 21173938
TI  - Chronic thrombotic scarring in patients with acute deep venous thrombosis of the
      lower limbs.
AB  - Some patients with acute deep venous thrombosis of the lower limbs may present
      risk factors for recurrent disease. AIMS: To analyze the most important
      conditions related to recurrent deep venous thrombosis of the lower limbs, other
      than thrombophilias. PATIENTS AND METHODS: We examined 88 consecutive patients
      (47 males-53.41%, average age 64.9 +/-13.9 years) admitted to a Medical Clinic in
      2007. Duplex ultrasonography was performed to assess acute deep venous thrombosis
      and post-thrombotic syndrome. Anamnesis and physical examination were used to
      detect risk factors for recurrent disease. The 28 subjects with acute deep venous
      thrombosis and post-thrombotic syndrome were included in group A (31.82%). Group
      B comprised 60 patients (68.18%) with acute deep venous thrombosis without post
      thrombotic syndrome. RESULTS: Risk factors for recurrent disease in groups A and
      B were the following: personal history of deep venous thrombosis of the lower
      limbs (17 subjects versus 7, p<0.0001), varicose veins (14 vs 24, p=0.51),
      obesity (13 vs 18, p=0.21), malignancy (6 vs 8, p=0.25), chronic obstructive lung
      disease (5 vs 6, p=0.24), prolonged immobilization (1 vs 7, p=0.21), major
      surgery (1 vs 1, p=0.54), stroke (0 vs 3, p=0.62), family history of deep venous
      thrombosis, immobilizing plaster cast, and congestive heart failure (0 vs 1,
      p=0.54). Location of thrombi in patients in groups A and B was as follows: 18
      patients in group A vs 25 subjects in group B on the left side and 13 patients in
      group A vs 20 patients in group B on the right side (p=0.02). CONCLUSION: Post
      thrombotic syndrome correlated with personal history of deep venous thrombosis
      and previous deep venous thrombosis located in the left lower limb.

PMID- 21173939
TI  - The contribution of ultrasonography and sonoelastography in assessment of
      myositis.
AB  - AIMS: To analyze the utility of ultrasonography (US) in the assessment of
      inflammatory myopathies, and of sonoelastography in the assessment of the
      elasticity of skeletal muscle in myositis. MATERIAL AND METHODS: The study group
      comprised 24 patients with musculoskeletal pathology examined using Hitachi 8500
      EUB equipment with a 6.5-13 MHz transducer and software for elastography. The
      images were analyzed in conjunction with clinical and biochemical data. Using
      dedicated software for color information from the elastographic images, the
      average values for color intensity, hue and dispersion were calculated. RESULTS:
      After the correlation of US images with clinical and paraclinical data the
      highest average values for color parameters were encountered on the superior
      third of the thigh. There was a proportional concordance between the average
      values of the color parameters and serum creatine kinase and serum lactic
      dehydrogenase and there was no significant agreement between the average values
      of the color parameters and the erythrocyte sedimentation rate, positive
      rheumatoid factor or positive antinuclear antibody. CONCLUSIONS: The correlation
      between the quantitative colour parameters from the elastographic images and the
      laboratory studies suggest that sonoelastography could be an important tool in
      the management of the patients with myositis.

PMID- 21173940
TI  - Experimental model for measuring and characterisation of the dento-alveolar
      system using high frequencies ultrasound techniques.
AB  - AIMS: The main objective of the study was the realisation of an experimental
      model and evaluation to establish whether the high frequency ultrasound method
      can supply credible information concerning the structure of the periodontal
      tissues. MATERIALS AND METHODS: We used a 20 MHz, 2D transducer of Dermascan C
      (CORTEX TECHNOLOGY l) device for examining 20 teeth on 4 healthy pig mandibles.
      The examination was made in the lateral area of alveolar bones at the lingual
      surface. RESULTS: On the images obtained through this type of ultrasonography we
      identified the cortical bone, tooth crown, tooth root and fixed mucosa. On the
      images obtained with Dermascan C ver. 3.0 software, very accurate measurements of
      periodontal space width (mean= 0.45 mm, Std. Dev=0.078) and thickness of cortical
      bone (mean= 0.31 mm, Std. Dev=0.134) and fixed mucosa (mean= 0.91 mm, Std.
      Dev=0.176) were made. CONCLUSIONS: Considering the non-invasive nature of the
      ultrasound method for patients and for medical staff during examination, but also
      considering the advantages generated by the possibility of making exact
      measurements of different areas, this method could become a reliable alternative
      for X-ray examinations in patients with periodontal disease. If a miniaturized
      transducer would be available, it could be used for ultrasound periodontal
      assessment in humans.

PMID- 21173942
TI  - Femoral nerve blockade.
AB  - Femoral nerve blockade is the most widely performed lower limb block. Methods of
      femoral nerve blockade are briefly reviewed with particular reference to
      ultrasound guidance.

PMID- 21173941
TI  - Contrast enhanced ultrasound guidance: a new tool to improve accuracy in
      percutaneous biopsies.
AB  - The performance of percutaneous echoguided biopsy in the tumoral diagnosis is
      limited by several factors, among which tumor characteristics such as tumor type,
      size and location play an important role. With all the advantages offered by the
      ultrasound guidance, the overall sensitivity of this method in the tumoral
      diagnosis of tumor has remained around 90%. Contrast enhanced ultrasound guided
      percutaneous biopsy is a new developed technique aimed to increase the acurracy
      of percutaneous biopsies. With new ultrasound devices with split-screen mode,
      which displays both the CEUS and background B-mode US image simultaneously, on a
      single monitor, the procedure is technically feasible. CEUS guided percutaneous
      biopsy should be applied in large tumors with consistent necrosis, in
      hypovascular tumors or in those invisible or poorly visible to conventional
      ultrasound. The increased accuracy was demonstrated in liver tumors and in
      prostate adenocarcinoma.

PMID- 21173943
TI  - The role of contrast enhanced ultrasound (CEUS) in the assessment of liver
      nodules in patients with cirrhosis.
AB  - Liver cirrhosis is a major risk factor for the development of hepatocellular
      carcinoma, hence the need to screen those patients by means of liver ultrasound
      every 6 months. The differential diagnosis between a regenerative nodule, a
      dysplastic one and hepatocellular carcinoma is made based on a contrast imaging
      method (CEUS, MRI or CT) as they all have comparative sensitivities.

PMID- 21173945
TI  - Patent ductus arteriosus.
AB  - Patent ductus arteriosus (PDA) is a congenital disorder in heart, wherein the
      ductus arteriosus fails to close after birth. This leads to the generation of a
      left-to-right shunt, leading to pulmonary hypertension. Color Doppler
      echocardiography is essential for the diagnosis. The identification of a
      diastolic flow oriented in the opposite direction in the pulmonary artery
      finalizes the diagnosis. We present the case of a 4 year old patient with
      systolic and diastolic left parasternal lift, echographically diagnosed with
      patent ductus arteriosus. The typical echographic aspects for this cardiac
      malformation are thoroughly detailed.

PMID- 21173944
TI  - Ultrasound examination of normal gall bladder and biliary system.
AB  - Biliary system diseases are a common pathology in medical practice. A frequent
      situation in everyday practice is a patient with pain in the right upper
      quadrant, in which the suspicion of biliary disease is the first diagnosis to
      confirm or exclude. Ultrasound is a reliable method for the evaluation of the
      biliary system and is the first method of choice when a biliary disease is
      suspected. Ideally a correct examination of the gallbladder and the biliary tree
      is performed on fasting patients. The gallbladder is evaluated by means of right
      subcostal oblique sections while for the hilum evaluation sections perpendicular
      on the ribs are used. The structures are assessed regarding their size, wall
      thickness and content.

PMID- 21173946
TI  - Mixed hepatoblastoma in child. Case report.
AB  - Hepatoblastoma represents the child's most frequent malignant hepatic tumor. We
      present the case of a one-year old prematurely born patient with an abdominal
      mass. Ultrasound and CT scan demonstrated a solid hepatic tumor. Serum alpha
      fetoprotein level was increased. He presented thrombocytosis and a left lobe
      hepatectomy was performed. Pathological examination revealed complete excision of
      a mixed hepatoblastoma. Hepatic tumor at a child under 3 years old correlated
      with elevated serum alpha fetoprotein and thrombocytosis are almost patognomonic
      for hepatoblastoma. Complete surgery is the mainstay of therapy in
      hepatoblastoma.

PMID- 21173947
TI  - Focal, asymptomatic epididymal masses--B-mode and color Doppler sonographic
      evaluation. Case report.
AB  - We reported the case of an adult male with an extratesticular mass prove to be
      postoperative a chronic inflammatory process. The importance of B-mode and color
      Doppler sonography in the differential diagnosis and literature regarding
      epididymal nodules and tumors of the paratesticular structures (epididymis) is
      reviewed and discussed.

PMID- 21173949
TI  - Understanding the aggregation induced emission enhancement for a compound with
      excited state intramolecular proton transfer character.
AB  - A few of excited state intramolecular proton transfer (ESIPT) compounds have been
      discovered for their aggregation induced emission enhancement (AIEE). To
      understand the AIEE mechanism, an ESIPT compound BTHPB (N-(4-(benzo[d]thiazol-2
      yl)-3-hydroxyphenyl)benzamide) with simple structure was designed and
      synthesized. BTHPB showed apparent AIEE property and the emission efficiency was
      observed as high as 0.27 in the aggregates. On the basis of viscochromism
      experiments and calculations employing the linear coupling model, the restriction
      of the rotation between the two subunits taken place in ESIPT was considered as
      the main factor for the AIEE. The micro- and femtosecond transient absorption
      experiments offered evidence for the considerations. Additionally, we also
      observed a negative effect of aggregation on the fluorescence emission in the
      system. So the AIEE of ESIPT compound BTHPB originated from the combination
      effects of positive and negative factors induced by the aggregation.

PMID- 21173950
TI  - Mapping the frontier electronic structures of triphenylamine based organic dyes
      at TiO2 interfaces.
AB  - The frontier electronic structures of a series of organic dye molecules
      containing a triphenylamine moiety, a thiophene moiety and a cyanoacrylic acid
      moiety have been investigated by photoelectron spectroscopy (PES), X-ray
      absorption spectroscopy (XAS), X-ray emission spectroscopy (XES) and resonant
      photoelectron spectroscopy (RPES). The experimental results were compared to
      electronic structure calculations on the molecules, which are used to confirm and
      enrich the assignment of the spectra. The approach allows us to experimentally
      measure and interpret the basic valence energy level structure in the dye,
      including the highest occupied energy level and how it depends on the interaction
      between the different units. Based on N 1s X-ray absorption and emission spectra
      we also obtain insight into the structure of the excited states, the molecular
      orbital composition and dynamics. Together the results provide an experimentally
      determined energy level map useful in the design of these types of materials.
      Included are also results indicating femtosecond charge redistribution at the
      dye/TiO(2) interface.

PMID- 21173951
TI  - Four constitutional isomers of BMpillar[5]arene: synthesis, crystal structures
      and complexation with n-octyltrimethyl ammonium hexafluorophosphate.
AB  - Four constitutional isomers of BMpillar[5]arene were prepared from 1-butoxy-4
      methoxybenzene and they showed different binding abilities with n-octyltrimethyl
      ammonium hexafluorophosphate.

PMID- 21173952
TI  - Continuous flow thermolysis of azidoacrylates for the synthesis of heterocycles
      and pharmaceutical intermediates.
AB  - An efficient, safe and scalable procedure for the continuous flow thermolysis of
      azidoacrylates to yield indoles has been developed and was applied to the
      synthesis of related heterocycles. The scalability of the process was
      demonstrated in the continuous flow synthesis of a precursor to the DAAO
      inhibitor 4H-furo[3,2-b]pyrrole-5-carboxylic acid.

PMID- 21173958
TI  - GC-MS and HPLC methods for peroxynitrite (ONOO- and O15NOO-) analysis: a study on
      stability, decomposition to nitrite and nitrate, laboratory synthesis, and
      formation of peroxynitrite from S-nitrosoglutathione (GSNO) and KO2.
AB  - Nitric oxide (NO) and superoxide (O(2)(-)) are ubiquitous in nature. Their
      reaction product peroxynitrite (ONOO(-)) and notably its conjugated peroxynitrous
      acid (ONOOH) are highly unstable in aqueous phase. ONOO(-)/ONOOH (referred to as
      peroxynitrite) isomerize and decompose to NO(3)(-), NO(2)(-) and O(2). Here, we
      report for the first time GC-MS and HPLC methods for the analysis of
      peroxynitrite in aqueous solution. For GC-MS analysis peroxynitrite in alkaline
      solution was derivatized to a pentafluorobenzyl derivative using
      pentafluorobenzyl bromide. O(15)NOO(-) was synthesized from H(2)O(2) and
      (15)NO(2)(-) and used as internal standard. HPLC analysis was performed on
      stationary phases consisting of Nucleosil(r) 100-5C(18)AB or Nucleodur(r) C(18)
      Gravity. The mobile phase consisted of a 10 mM aqueous solution of
      tetrabutylammonium hydrogen sulfate and had a pH value of 11.5. UV absorbance
      detection at 300 nm was used. HPLC allows simultaneous analysis of ONOO(-),
      NO(2)(-) and NO(3)(-). The GC-MS and HPLC methods were used to study stability,
      synthesis, formation from S-[(15)N]nitrosoglutathione (GS(15)NO) and KO(2), and
      isomerization/decomposition of peroxynitrite to NO(2)(-) and NO(3)(-) in aqueous
      buffer.

PMID- 21173953
TI  - A new dehydrogenase from Clostridium acetobutylicum for asymmetric synthesis:
      dynamic reductive kinetic resolution entry into the Taxotere side chain.
AB  - An NADP-dependent alcohol dehydrogenase from Clostridium acetobutylicum (CaADH)
      has been expressed and characterized. CaADH enantioselectively reduces aromatic
      alpha-, beta- and gamma-keto esters to the corresponding D-hydroxy esters and
      provides a building block for the Taxotere side chain (95% yield, 95% de, 99% ee)
      by dynamic reductive kinetic resolution (DYRKR).

PMID- 21173959
TI  - Fluorescence-monitored zero dead-volume nanoLC-microESI-QIT-TOF MS for analysis
      of fluorescently tagged glycosphingolipids.
AB  - An analysis of the glycan processing event is of particular importance to
      understand the nontemplate dependent synthetic mechanism of the multiple
      glycosylation reactions taking place in the Golgi apparatus in connection with
      the post-translational modification of biomolecules. In our efforts to address
      the issue, we constructed an analysis platform using nano-liquid chromatography
      (LC), which also worked as a spray tip, with an optical-fiber-based blue (470 nm)
      light emitting diode (LED)-induced fluorescence (520 nm) detector coupled with a
      microelectrospray ionization (ESI)-quadrupole ion trap (QIT)-time of flight (TOF)
      mass spectrometer (MS). This system was designed to enable both quantitative and
      qualitative analyses of fluorescently tagged molecules such as BODIPY-tagged
      lactosylceramide. Owing to the zero dead volume after LC separation, an extremely
      high sensitivity was achieved for the quantitative analysis (260 amol). It was
      also shown that a simultaneous online structural analysis based on MS could be
      achieved for the same quantity of analyte. To further demonstrate its potential,
      an enzymatic reaction of fluorescently tagged lactosylceramide using
      sialyltransferase was carried out, and the conversion yield was obtained on the
      basis of fluorescence detection. In addition, the structural details of a
      product, sialyl lactosylceramide, were obtained by MS and MS/MS analyses.

PMID- 21173960
TI  - Multiple functionalization of single-walled carbon nanotubes by dip coating.
AB  - Single walled carbon nanotubes were functionalized with different functionalities
      by simple dip coating. This fast and reproducible procedure was realized with
      nanotube coated electrodes for the construction of polyvalent biosensors. Three
      different pyrene derivatives were attached to the nanotube sidewalls by pi
      stacking interactions in a one-step reaction.

PMID- 21173961
TI  - One-step ultrasensitive detection of microRNAs with loop-mediated isothermal
      amplification (LAMP).
AB  - An ultrasensitive microRNA assay was developed with one-step loop-mediated
      isothermal amplification (LAMP) initiated by the target microRNA.

PMID- 21173962
TI  - Transparent and conductive thin films of graphene/polyaniline nanocomposites
      prepared through interfacial polymerization.
AB  - This communication reports a simple, one-pot procedure for the synthesis and
      processing of transparent and conductive thin films of graphene/polyaniline
      nanocomposites based on an interfacial polymerization. Thin films presenting
      transmittance of 89% and sheet resistance of 60.6 Omega sq(-1) are spontaneously
      obtained and can be easily transferred to suitable substrates.

PMID- 21173963
TI  - End-stapled homo and hetero collagen triple helices: a click chemistry approach.
AB  - A CuAAC reaction was established for modular synthesis of end-stapled homo- and
      hetero-triple helical peptides, generating "clicked" macro-assemblies with
      enhanced thermal stability.

PMID- 21173964
TI  - Synthesis and characterization of bispyrrolidine derivatives of H2@C60:
      differentiation of isomers using 1H NMR spectroscopy of endohedral H2.
AB  - Bisadduct isomers of a H(2)@C(60) derivative with nitroxide addends have been
      synthesized, isolated and characterized. The (1)H NMRs of endohedral H(2) of the
      major isomers show well-separated chemical shifts, which could be useful for
      structural assignment and identification of the purity of the C(60) bisadduct
      isomers.

PMID- 21173965
TI  - Microenvironment-switchable singlet oxygen generation by axially-coordinated
      hydrophilic ruthenium phthalocyanine dendrimers.
AB  - A series of new metallodendrimers built around a ruthenium phthalocyanine core
      has been prepared. Employing a convergent synthetic strategy, pyridine-containing
      ligands were prepared and then assembled onto the ruthenium phthalocyanine
      through axial ligand coordination. The growing shell of oligoethylene glycol
      chains surrounding the lipophilic core allows solubilisation in water.
      Photophysical studies show that all the metallodendrimers are strongly
      phosphorescent and the deactivation pathway of their triplet state depends on the
      medium in which the compounds are dissolved. On one hand, quenching of the
      triplet state by the dendritic shell is observed and found to be substantially
      enhanced in aqueous media. On the other, the dendrimer shields the phthalocyanine
      from oxygen. This notwithstanding, the phthalocyanines are able to generate
      singlet oxygen in less polar environments such as in CHCl(3) or THF solution,
      while in water the generation of singlet oxygen is almost completely switched
      off.

PMID- 21173966
TI  - Enhanced photocatalytic activity of mesoporous TiO2 aggregates by embedding
      carbon nanotubes as electron-transfer channel.
AB  - Mesoporous multiwalled carbon nanotubes/titanium dioxide (CNTs/TiO(2))
      nanocomposites with low loading amounts (0-0.5 wt%) of CNTs embedded inside
      mesoporous TiO(2) aggregates has been prepared by a simple one-pot hydrothermal
      method using titanium sulfate as titanium source. The as-prepared CNTs/TiO(2)
      samples are carefully characterized, analyzed and discussed. In contrast to
      previous reports with high CNT loading, our results indicate that a low CNT
      loading slightly influences the textural properties (including crystallite size,
      degree of crystallinity, specific surface areas, and pore volume etc.) and UV
      light absorption of the mesoporous TiO(2) aggregates. The SEM and TEM results
      demonstrate that the CNTs are mostly embedded in the mesoporous TiO(2)
      aggregates. Moreover, chemical bonds are formed at the interface between CNTs and
      TiO(2), which is confirmed by the Raman, IR and XPS analyses. Significantly, we
      point out that PL analysis in terms of intensity of PL signals seems to not be a
      reliable way to monitor the recombination rate in the CNTs/TiO(2) composite, due
      to the quenching effect of CNTs. Instead, the analysis of transient photocurrent
      responses is introduced, which definitely reflects CNTs as fast electron transfer
      channels in chemically-bonded CNTs/TiO(2) composites with low CNT loading.
      Notably, the positive synergy effects of CNTs and TiO(2) depend on both the CNT
      loading amount and the state of interfacial contacts. In our study, only these
      chemically bonded CNTs/TiO(2) nanocomposites with appropriate loading amounts
      (<0.1 wt%) favor the separation of photogenerated electron-hole pairs and
      decrease their recombination rate and thus display significantly enhanced
      photocatalytic activity for degrading acetone in air under UV irradiation, as
      compared with pristine TiO(2) counterparts and commercial P25 photocatalyst. In
      contrast, a high CNT loading (>0.1 wt%) results in a decrease in photocatalytic
      activity; a simple mechanical mixing of CNTs and TiO(2) without forming chemical
      bonds at the interface also results in inferior photocatalytic performance.

PMID- 21173967
TI  - Anharmonic overtone and combination states of glycine and two model peptides
      examined by vibrational self-consistent field theory.
AB  - In this paper, the application of the vibrational self-consistent field (VSCF)
      and correction-corrected VSCF methods for calculating anharmonic parameters,
      including transition frequency, transition intensity and dipole, and vibrational
      anharmonicity of 3N-6 normal modes for formamide, glycine, N-methylacetamide and
      their deuterated derivatives are explored mainly at the level of density
      functional theory. The computed fundamental anharmonic frequencies are found to
      be in reasonable agreement with experimental results. Diagonal anharmonicities of
      the second overtone states were examined for multiple normal modes, whose
      magnitudes were found to correlate well with those of the first overtone states
      in the three small molecules. The results show that the VSCF-based approach can
      be utilized to predict anharmonic parameters of higher vibrational states that
      are essential to understanding multi-pulse infrared nonlinear experiments of
      peptides.

PMID- 21173968
TI  - Dissimilar interaction of CB1/CB2 with lipid bilayers as revealed by molecular
      dynamics simulation.
AB  - Cannabinoid receptors CB1 and CB2 are a striking class of transmembrane proteins
      involved in a high number of important biological processes. In spite of the
      inherent similarity (40% in aminoacid sequence) these receptors are found in
      different cell environments. In addition to this, CB1 activity has been
      intimately associated with lipid rafts whereas CB2 has not. In this work we have
      performed a 50 nanosecond molecular dynamics simulation of the inactive
      conformations of both receptors inserted in a POPC lipid bilayer. Although in
      both cases the overall protein structure is maintained along the entire
      simulation we have found important differences in the protein-lipid interaction.
      While CB1 tends to distort the lipid bilayer regularity, especially in the
      extracellular moiety, CB2 has a minor influence on the lipid distribution along
      the plane of the bilayer. This observation is consistent with some experimental
      facts observed in these cannabinoid receptors with regard to lipid/protein
      interaction.

PMID- 21173969
TI  - X-ray spectroscopy of electrochemically deposited iridium oxide films: detection
      of multiple sites through structural disorder.
AB  - We report the results of X-ray absorption spectroscopy studies on
      electrochemically deposited iridium oxide films. The emphasis of the study is the
      correlation of X-ray derived structural data with electrochemically controlled
      charge state. Data were acquired for films subject to redox cycling in neutral
      and alkaline aqueous media. In both cases, cyclic voltammetric responses show two
      redox couples, coulometrically of roughly equal magnitude. Assays of the iridium
      population (based on the iridium L(3) absorption edge amplitude) and the charge
      injected (based on integration of the voltammetric response) show that overall an
      average of ca. one electron per iridium atom is transferred. The absorption edge
      shifts indicate that the formal charge on the iridium changes, on average, from
      ca. 3.5+ to ca. 4.5+ across the entire process. EXAFS-derived changes in mean Ir
      O distance and their mean square variation have been interpreted in terms of a
      two-site model, in which the two types of site have distinct redox potentials.
      Variations of local structure and disorder with potential are discussed and a
      generic model for structural disorder (parameterized via Debye-Waller factor)
      with diagnostic capability is developed.

PMID- 21173970
TI  - Factors controlling charge recombination under dark and light conditions in dye
      sensitised solar cells.
AB  - A simple and powerful approach for assessing the recombination losses in dye
      sensitised solar cells (DSSCs) across the current voltage curve (j-V) as a
      function of TiO(2) electron concentration (n) is demonstrated. The total flux of
      electrons recombining with iodine species in the electrolyte and oxidised dye
      molecules can be thought of as a recombination current density, defined as j(rec)
      = j(inj)-j where j(inj) is the current of electrons injected from optically
      excited dye states and j is the current density collected at cell voltage (V).
      The electron concentration at any given operating conditions is determined by
      charge extraction. This allows comparison of factors influencing electron
      recombination rates at matched n. We show that j(rec) is typically 2-3 times
      higher under 1 sun equivalent illumination (j(inj) > 0) relative to dark (j(inj)
      = 0) conditions. This difference was increased by increasing light intensity,
      electrolyte iodine concentration and electrolyte solvent viscosity. The
      difference was reduced by increasing the electrolyte iodide concentration and
      increasing the temperature. These results allowed us to verify a numerical model
      of complete operational cells (Barnes et al., Phys. Chem. Chem. Phys., DOI:
      10.1039/c0cp01554g) and to relate the differences in j(rec) to physical processes
      in the devices. The difference between j(rec) in the light and dark can be
      explained by two factors: (1) an increase in the concentration of electron
      acceptor species (I(3)(-) and/or I(2)) when current is flowing under illumination
      relative to dark conditions where the current is flowing in the opposite
      direction, and (2) a non-trivial contribution from electron recombination to
      oxidised dye molecules under light conditions. More generally, the technique
      helps to assign the observed relationship between the components, processing and
      performance of DSSCs to more fundamental physical processes.

PMID- 21173971
TI  - Ground-state proton-transfer dynamics governed by configurational optimization.
AB  - The ground-state proton transfer (GSPT) of 7-hydroxyquinoline along a hydrogen
      bonded alcohol chain has been investigated in n-alkanes using time-resolved
      transient-absorption spectroscopy with variation of alcohols, media, isotopes,
      and temperatures. As a 7-hydroxyquinoline molecule associates with two alcohol
      molecules via hydrogen bonding to form a cyclic complex in a nonpolar aprotic
      medium, the intrinsic GSPT dynamics of the cyclic complex in a n-alkane has been
      observed directly without being interfered with by solvent association to form
      the cyclic complex. GSPT occurs concertedly without accumulating any reaction
      intermediate and yet asymmetrically with a rate-determining tunneling process.
      Both the rate constant and the kinetic isotope effect of GSPT increase rapidly
      with the proton-donating ability of the alcohol but decrease greatly with the
      molecular size of the alcohol. The reorganization of the hydrogen-bond bridge to
      form an optimal precursor configuration for efficient proton tunneling takes
      place prior to intrinsic GSPT, and configurational optimization becomes more
      important as the molecular size of the alcohol increases. Consequently, the
      larger contribution of configurational optimization to GSPT leads to the weaker
      asymmetric character of GSPT.

PMID- 21173972
TI  - Adsorption, structure and dynamics of benzene in ordered and disordered porous
      carbons.
AB  - Molecular simulations are used to study the adsorption, structure, and dynamics
      of benzene at 298 K in atomistic models of ordered and disordered nanoporous
      carbons. The ordered porous carbon is a regular slit pore made up of graphene
      sheets. The disordered porous carbon is a structural model that reproduces the
      morphological (pore shape) and topological (pore connectivity) disorder of
      saccharose-based porous carbons. As expected for pores of a regular geometry, the
      filling occurs at well-defined pressures which are an increasing function of the
      pore width H. In contrast, in qualitative agreement with experimental data for
      activated carbon fibers, the filling of the disordered carbon is continuous and
      spans over a large pressure range. The structure and dynamics of benzene in the
      disordered carbon also strongly depart from that for the slit pore geometry.
      While benzene in the slit graphite nanopores exhibits significant layering,
      benzene in the disordered porous carbon exhibits a liquid-like structure very
      close to its bulk counterpart. Both the ordering and self-diffusivity of benzene
      in the graphite nanopores depend in a complex manner on the pore width. The
      dynamics is either slower or faster than its bulk counterpart; our data show that
      the self-diffusivity decreases as the number of confined layers n divided by the
      pore width H increases (except for very small pore sizes for which benzene
      crystallizes and is necessarily slower than the liquid phase). The dynamics of
      benzene in the disordered porous carbon is isotropic and is much slower than that
      for the graphite slit nanopores (even with the smallest slit nanopore considered
      in this work). The results above show that the adsorption, structure, and
      dynamics of benzene confined in disordered porous carbons cannot be described in
      simple terms using an ideal model such as the slit pore geometry.

PMID- 21173973
TI  - Manganese oxide-based materials as electrochemical supercapacitor electrodes.
AB  - Electrochemical supercapacitors (ECs), characteristic of high power and
      reasonably high energy densities, have become a versatile solution to various
      emerging energy applications. This critical review describes some materials
      science aspects on manganese oxide-based materials for these applications,
      primarily including the strategic design and fabrication of these electrode
      materials. Nanostructurization, chemical modification and incorporation with high
      surface area, conductive nanoarchitectures are the three major strategies in the
      development of high-performance manganese oxide-based electrodes for EC
      applications. Numerous works reviewed herein have shown enhanced electrochemical
      performance in the manganese oxide-based electrode materials. However, many
      fundamental questions remain unanswered, particularly with respect to
      characterization and understanding of electron transfer and atomic transport of
      the electrochemical interface processes within the manganese oxide-based
      electrodes. In order to fully exploit the potential of manganese oxide-based
      electrode materials, an unambiguous appreciation of these basic questions and
      optimization of synthesis parameters and material properties are critical for the
      further development of EC devices (233 references).

PMID- 21173975
TI  - Quantifying signal changes in nano-wire based biosensors.
AB  - In this work, we present a computational methodology for predicting the change in
      signal (conductance sensitivity) of a nano-BioFET sensor (a sensor based on a
      biomolecule binding another biomolecule attached to a nano-wire field effect
      transistor) upon binding its target molecule. The methodology is a combination of
      the screening model of surface charge sensors in liquids developed by Brandbyge
      and co-workers [Sorensen et al., Appl. Phys. Lett., 2007, 91, 102105], with the
      PROPKA method for predicting the pH-dependent charge of proteins and protein
      ligand complexes, developed by Jensen and co-workers [Li et al., Proteins:
      Struct., Funct., Bioinf., 2005, 61, 704-721, Bas et al., Proteins: Struct.,
      Funct., Bioinf., 2008, 73, 765-783]. The predicted change in conductance
      sensitivity based on this methodology is compared to previously published data on
      nano-BioFET sensors obtained by other groups. In addition, the conductance
      sensitivity dependence from various parameters is explored for a standard wire,
      representative of a typical experimental setup. In general, the experimental data
      can be reproduced with sufficient accuracy to help interpret them. The method has
      the potential for even more quantitative predictions when key experimental
      parameters (such as the charge carrier density of the nano-wire or receptor
      density on the device surface) can be determined (and reported) more accurately.

PMID- 21173974
TI  - Comparative analysis of nuclear estrogen receptor alpha and beta interactomes in
      breast cancer cells.
AB  - Estrogen Receptor alpha and beta (ER-alpha and -beta) are members of the nuclear
      receptor family of transcriptional regulators with distinct roles in mediating
      estrogen dependent breast cancer cell growth and differentiation. Following
      activation by the hormone, these proteins undergo conformation changes and
      accumulate in the nucleus, where they bind to chromatin at regulatory sites as
      homo- and/or heterodimers and assemble in large multiprotein complexes. Although
      the two ERs share a conserved structure, they exert specific and distinct
      functional roles in normal and transformed mammary epithelial cells and other
      cell types. To investigate the molecular bases of such differences, we performed
      a comparative computational analysis of the nuclear interactomes of the two ER
      subtypes, exploiting two datasets of receptor interacting proteins identified in
      breast cancer cell nuclei by Tandem Affinity Purification for their ability to
      associate in vivo with ligand-activated ER-alpha and/or ER-beta. These datasets
      comprise 498 proteins, of which only 70 are common to both ERs, suggesting that
      differences in the nature of the two ER interactomes are likely to sustain the
      distinct roles of the two receptor subtypes. Functional characterization of the
      two interactomes and their topological analysis, considering node degree and
      closeness of the networks, confirmed this possibility. Indeed, clustering and
      network dissection highlighted the presence of distinct and ER subtype-specific
      subnetworks endowed with defined functions. Altogether, these data provide new
      insights on the protein-protein interaction networks controlled by ER-alpha and 
      beta that mediate their ability to transduce estrogen signaling in breast cancer
      cells.

PMID- 21173976
TI  - Insights in the rational design of synthetic multivalent glycoconjugates as
      lectin ligands.
AB  - Much effort has been made during the last decade to design lectin inhibitors as
      therapeutics against viral and bacterial adhesion or to control biological
      functions. The chemical strategy adopted generally consists in the tethering of
      several binding epitopes on a common scaffold. The resulting multivalent
      glycoconjugates often display a much higher binding affinity for their targets
      compared to their monovalent counterparts, a phenomenon designed as the "cluster"
      or "multivalent effect". Hundreds of multimeric architectures have been designed
      so far and some of the compounds displayed impressive gains in binding affinity
      or in vivo efficiency. Progress in this area is, however, hampered by the
      difficulty to predict the potency of the new multimeric inhibitors. This review
      presents the recent efforts to probe the important structural features of the
      synthetic multivalent glycoconjugates for a tight binding with specific lectins.
      We hope that the reported examples will aid the reader to design efficient
      multivalent ligands in a more predictable way.

PMID- 21173977
TI  - Copper(I)-mediated preparation of new pyrano[3',4':4,5]imidazo[1,2-a]pyridin-1
      one compounds under mild palladium-free conditions.
AB  - A general and efficient Cu(I)-mediated cross-coupling and heterocyclization
      reaction of 3-iodoimidazo[1,2-a]pyridine-2-carboxylic acid, and terminal alkynes
      was developed under very mild conditions. This method allows the introduction in
      one pot of a third ring fused in positions 2 and 3 of the imidazo[1,2-a]pyridine
      core with reasonable yields and total regioselectivity. This procedure does not
      require the use of any expensive supplementary additives, and is palladium-free.

PMID- 21173978
TI  - Chiral lutetium benzamidinate complexes.
AB  - Enantiomerically pure lutetium complexes were synthesized as the first rare earth
      metal complexes containing a chiral amidinate ligand. The catalytic activity and
      the enantioselectivity in hydroamination reactions were studied.

PMID- 21173979
TI  - Ruthenium nanoparticles embedded in mesoporous carbon microfibers: preparation,
      characterization and catalytic properties in the hydrogenation of D-glucose.
AB  - Ruthenium (Ru) nanoparticles dispersed in mesoporous carbon microfibers were
      prepared using alumina microfibers as the templates via a chemical vapour
      deposition (CVD) route. Characterized data showed that Ru nanoparticles were
      embedded in the mesoporous carbon matrix. The samples were found to possess a
      specific surface area as high as 750 m(2) g(-1), pore sizes in the range of 3-5
      nm, lengths in the range of 5-10 MUm, and a width of about 0.5 MUm. The Ru
      catalysts displayed a remarkably high catalytic activity and an excellent
      stability in the hydrogenation of D-glucose. The observed good catalyst
      performance is attributed to the carbon microfiber morphology, unblocked
      mesoporous structure, and the hydrogen spillover effect induced by the unique
      surface contact between the Ru nanoparticles and the carbon. In addition, the
      incorporation of nitrogen significantly improved the catalytic performance due to
      the enhanced hydrogen adsorption, better wettability, and modified electronic
      properties of the Ru.

PMID- 21173980
TI  - Hydrogen exchange mass spectrometry for studying protein structure and dynamics.
AB  - Hydrogen/deuterium exchange (HDX) mass spectrometry (MS) has become a key
      technique for monitoring structural and dynamic aspects of proteins in solution.
      This approach relies on the fact that exposure of a protein to D(2)O induces
      rapid amide H -> D exchange in disordered regions that lack stable hydrogen
      bonding. Tightly folded elements are much more protected from HDX, resulting in
      slow isotope exchange that is mediated by the structural dynamics ("breathing
      motions") of the protein. MS-based peptide mapping is a well established
      technique for measuring the mass shifts of individual protein segments. This
      tutorial review briefly discusses basic fundamentals of HDX/MS, before
      highlighting a number of recent developments and applications. Gas phase
      fragmentation strategies represent a promising alternative to the traditional
      proteolysis-based approach, but experimentalists have to be aware of scrambling
      phenomena that can be encountered under certain conditions. Electron-based
      dissociation methods provide a solution to this problem. We also discuss recent
      advances that facilitate the applicability of HDX/MS to membrane proteins, and to
      the characterization of short-lived protein folding intermediates. It is hoped
      that this review will provide a starting point for novices, as well as a useful
      reference for practitioners, who require an overview of some recent trends in
      HDX/MS.

PMID- 21173981
TI  - From diatoms to silica-based biohybrids.
AB  - This critical review shows that diatoms can be a source of inspiration for the
      synthesis of advanced nanostructured biohybrids. These single cell microalgae are
      living inside a porous silica shell called 'frustule'. Mimicking this model,
      silica-based biohybrids have been produced via the so-called sol-gel process.
      Biomolecules such as proteins, enzymes or antibodies can be trapped within a
      silica matrix leading to hybrid biosensors and bioreactors. Whole cells remain
      viable and retain their metabolic activity leading to the formation of living
      biohybrids that offer new possibilities in the field of biotechnology and
      nanomedicine. Diatom frustules exhibit an incredible variety of sophisticated
      shapes; they can be used as 3D hierarchically structured materials for the
      realization of sensors, photonic devices or microfluidics. They can also be a
      model for the bio-templated synthesis of nanostructured materials. Diatom
      nanotechnology is becoming a new field of research where biologists and materials
      scientists are working together! (125 references).

PMID- 21173983
TI  - Magnetically recoverable SiO2-coated Fe3O4 nanoparticles: a new platform for
      asymmetric transfer hydrogenation of aromatic ketones in aqueous medium.
AB  - A magnetically recoverable chiral rhodium catalyst exhibited excellent catalytic
      activity and enantioselectivity in asymmetric transfer hydrogenation of aromatic
      ketones in aqueous medium, which could be recovered easily via a small magnet and
      used repetitively ten times without obviously affecting its enantioselectivity.

PMID- 21173982
TI  - Accumulation of rare earth elements in human bone within the lifespan.
AB  - For the first time, the contents of rare earth elements (REEs) in a rib bone of a
      healthy human were determined. The mean value of the contents of Ce, Dy, Er, Gd,
      La, Nd, Pr, Sm, Tb, and Yb (10 elements out of 17 total REEs), as well as the
      upper limit of means for Ho, Lu, Tm, and Y (4 elements) were measured in the rib
      bone tissue of 38 females and 42 males (15 to 55 years old) using inductively
      coupled plasma mass spectrometry (ICP-MS). We found age-related accumulation of
      REEs in the bone tissue of healthy individuals who lived in a non-industrial
      region. It was calculated that during a lifespan the content of REEs in a
      skeleton of non-industrial region residents may increase by one to two orders of
      magnitude. Using our results as indicative normal values and published data we
      estimated relative Gd accumulation in the bone tissue of patients according to
      magnetic resonance imaging with contrast agent and La accumulation in the bone
      tissue of patients receiving hemodialysis after treatment with lanthanum
      carbonate as a phosphate binder. It was shown that after such procedures contents
      of Gd and La in the bone tissue of patients are two to three orders of magnitude
      higher than normal levels. In our opinion, REEs incorporation may affect bone
      quality and health similar to other potentially toxic trace metals. The impact of
      elevated REEs content on bone physiology, biochemistry and morphology requires
      further investigation.

PMID- 21173984
TI  - Solid phase strain promoted "click" modification of DNA via [3+2]-nitrile oxide
      cyclooctyne cycloadditions.
AB  - Rapid, catalyst free, solid phase modification of DNA by strain promoted
      cyclooctyne-nitrile oxide click chemistry is reported; the reaction is
      characterised by mild conditions, occurring in an aqueous environment under
      atmospheric conditions at room temperature and is complete in 10 minutes.

PMID- 21173985
TI  - An investigation into the origin of the dramatically reduced reactivity of
      peptide-prolyl-thioesters in native chemical ligation.
AB  - The low reactivity of peptide-prolyl-thioesters in native chemical ligation is
      not due to steric effects at the beta-carbon, but rather to the presence of a
      carbonyl moiety on the nitrogen atom of the proline.

PMID- 21173986
TI  - Copper(II) complexes of hybrid hydroxyquinoline-thiosemicarbazone ligands:
      GSK3beta inhibition due to intracellular delivery of copper.
AB  - Cognitive decline associated with Alzheimer's disease appears to be related to
      the hyper-phosphorylation of the protein tau as a consequence of increased
      activity of glycogen synthase kinase 3beta (GSK3beta), and subsequent formation
      of neurotoxic neurofibrillary tangles. Abberant metal ion homeostasis,
      particularly involving copper has been implicitly linked to the pathogenesis of
      the disease. Increasing intracellular copper concentrations has been found to
      trigger pathways that result in inhibition of GSK3beta. The syntheses and
      characterisation of tetradentate hybrid hydroxyquinoline-thiosemicarbazone
      proligands is presented. The ligands form stable complexes with Cu(II) where the
      copper ion is four coordinate and essentially square planar as characterised by
      single crystal X-ray crystallography. The reduction of the metal ion to Cu(I) has
      been studied by electrochemical techniques and occurs at potentials that permit
      intracellular reduction. The new complexes show class dependent cell membrane
      permeability in neuronal-like SH-SY5Y cells with subsequent increases in
      intracellular copper concentrations. The increased intracellular copper results
      in a dose-dependent inhibition (phosphorylation) of GSK3beta.

PMID- 21173987
TI  - Surfactant-assisted one-pot synthesis of superparamagnetic magnetite nanoparticle
      clusters with tunable cluster size and magnetic field sensitivity.
AB  - Magnetic nanoparticles (MNPs) have many potential biomedical applications.
      Improvements in their magnetic properties and solubility are necessary for these
      applications to realize their full potential. In this study, MNPs in the form of
      raspberry-like magnetite (Fe(3)O(4)) nanoparticle clusters, consisting of tiny
      Fe(3)O(4) particles with a diameter of approximately 20 nm, were prepared under
      hydrothermal conditions at 200  degrees C in the presence of 3,4
      dihydroxyhydroxysinnamic acid (DHCA). The primary particles were connected by
      DHCA molecules to form the clusters, which were well dispersed in water media
      because a COOH group from DHCA appeared on their surfaces. The cluster size could
      be tuned from 50 to 400 nm without changing the primary particle size by
      controlling the reaction time. Therefore, all prepared clusters displayed
      superparamagnetic properties at room temperature. In addition, the sensitivity of
      Fe(3)O(4) to an external magnetic field could also be controlled by the cluster
      size.

PMID- 21173988
TI  - Tuning emission wavelength and redox properties through position of the
      substituent in iridium(III) cyclometallated complexes.
AB  - Cyclometallated phenyls with substituents para to the metal have a larger impact
      on the redox potentials and emission of complexes [Ir(R-ppz)(2)(bipy)][PF(6)]
      than substituents at the meta position and hence enable tuning of emission
      wavelength over a wider range using the same substituent.

PMID- 21173989
TI  - Synthesis of single crystalline CdS nanocombs and their application in photo
      sensitive field emission switches.
AB  - Single crystalline CdS nanocombs were synthesized by a thermal evaporation route.
      The photo-sensitive field emission current shows a reproducible switching
      behavior, with a rise in current level of nearly five times the initial preset
      value of ~1 MUA. An ultra low turn-on field, required to draw an emission current
      density of ~0.1 MUA cm(-2) (100 nA), is found to be ~0.26 V MUm(-1) (260 V),
      which is much lower than the reported values for various other CdS
      nanostructures. Upon illumination with visible light the CdS nanocombs act as a
      photo field emission switch. At an applied field of ~0.65 V MUm(-1) the current
      densities are observed to be ~14.6 MUA cm(-2) and ~26.9 MUA cm(-2), without and
      with light illumination, respectively. The average emission current is seen to be
      stable over the duration of measurement for two preset values. The high
      sensitivity and fast response in the visible range indicates that the CdS
      nanocombs can be used as a photo-sensitive field emitting switch in device
      applications, and also in pulsed electron beam technology.

PMID- 21173990
TI  - Probing the stereoselectivity of P-glycoprotein-synthesis, biological activity
      and ligand docking studies of a set of enantiopure benzopyrano[3,4
      b][1,4]oxazines.
AB  - A series of enantiomerically pure benzopyrano[3,4-b][1,4]oxazines have been
      synthesised and tested for their ability to inhibit P-glycoprotein. Reducing the
      conformational flexibility of the molecules leads to remarkable differences in
      the activity of diastereoisomers. Docking studies into a homology model of human
      P-gp provide first insights into potential binding areas for these compounds.

PMID- 21173991
TI  - In situ encapsulating silver nanocrystals into hydrogels. A "green" signaling
      platform for thiol-containing amino acids or small peptides.
AB  - We found that Ag(I) could serve as a "bridging agent" for triggering sodium
      carboxymethylcellulose (NaCMC) solution to form a hydrogel which enabled Ag
      nanocrystals to be in situ produced and encapsulated into the stable gel matrix
      by means of photoreduction; the conceptual system could act as a novel signaling
      platform for thiol-containing amino acids or small peptides, operating in a "self
      assembly and disassembly" model.

PMID- 21173992
TI  - Facile preparation and upconversion luminescence of graphene quantum dots.
AB  - A facile hydrazine hydrate reduction of graphene oxide (GO) with surface
      passivated by a polyethylene glycol (PEG) method for the fabrication of graphene
      quantum dots (GQDs) with frequency upconverted emission is presented. And we
      speculate on the upconversion luminescence due to the anti-Stokes
      photoluminescence (ASPL), where the deltaE between the pi and sigma orbitals is
      near 1.1 eV.

PMID- 21173993
TI  - Nanomechanics for MEMS: a structural design perspective.
AB  - Nanomechanics and structural design of MEMS are intimately tied together. As
      mechanical properties of hard materials are found to be strongly sample-size
      dependent, new criteria are in demand for size-dependent structural analysis and
      design of MEMS components. The paper offers a critical survey of some of the most
      interesting and challenging advances in nanomechanics of metals from a MEMS
      design standpoint. The emphasis is not just on sample size effects in intrinsic
      properties (in plasticity, elasticity and fracture) but also on extrinsic effects
      arising in material testing of super hard nano-sized samples and crucially
      affecting MEMS performance if discarded.

PMID- 21173998
TI  - Nanostructured nanoparticles of self-assembled lipid pro-drugs as a route to
      improved chemotherapeutic agents.
AB  - We demonstrate that oral delivery of self-assembled nanostructured nanoparticles
      consisting of 5-fluorouracil (5-FU) lipid prodrugs results in a highly effective,
      target-activated, chemotherapeutic agent, and offers significantly enhanced
      efficacy over a commercially available alternative that does not self-assemble.
      The lipid prodrug nanoparticles have been found to significantly slow the growth
      of a highly aggressive mouse 4T1 breast tumour, and essentially halt the growth
      of a human MDA-MB-231 breast tumour in mouse xenografts. Systemic toxicity is
      avoided as prodrug activation requires a three-step, enzymatic conversion to 5
      FU, with the third step occurring preferentially at the tumour site.
      Additionally, differences in the lipid prodrug chemical structure and internal
      nanostructure of the nanoparticle dictate the enzymatic conversion rate and can
      be used to control sustained release profiles. Thus, we have developed novel oral
      nanomedicines that combine sustained release properties with target-selective
      activation.

PMID- 21173999
TI  - A prospective study of an aggressive warfarin dosing algorithm to reach and
      maintain INR 2 to 3 after heart valve surgery.
AB  - Good anticoagulation control in patients during the first months after heart
      valve surgery is important to prevent thrombotic complications. This is difficult
      to achieve, partly because the sensitivity to warfarin decreases progressively
      during approximately three months after valve surgery. A recently developed,
      simple but aggressive algorithm might improve anticoagulation control in this
      patient group. It was the objective of this study to evaluate the level of
      anticoagulation control when a specialised anticoagulation clinic changed from
      empirical dosing to the use of this new algorithm. In a before-and-after design,
      a cohort of consecutive patients managed with a new, aggressive dosing algorithm
      ('Algorithm cohort') was compared to a 'Retrospective cohort' of similar patients
      dosed empirically. Primary endpoint was individual time in therapeutic range
      (ITTR) during the first three months of warfarin therapy. Secondary endpoints
      included proportion of extreme International Normalised Ratio (INR) results,
      thrombotic and bleeding complications. Ninety-eight patients were included in the
      Algorithm cohort, 94 of whom were warfarin-naive. Two hundred patients were
      included in the Retrospective cohort. Mean ITTR was 60.1% in the Algorithm cohort
      versus 48.7% in the Retrospective cohort (p <0.001). Patients in the Algorithm
      cohort spent 0.5% of time at an INR >5, versus 0.2 % in the Retrospective cohort.
      There was no major bleeding in either cohort; one patient in each cohort had a
      thrombotic complication. We demonstrate an improvement of the level of
      anticoagulation control with the use of a condition-specific, aggressive
      algorithm, as compared to standard dosing, in patients after heart valve surgery.

PMID- 21174000
TI  - Identification of three novel plasminogen (PLG) gene mutations in a series of 23
      patients with low PLG activity.
AB  - Inherited severe hypoplasminogenaemia is a multisystemic disorder leading to
      deficient extravascular fibrinolysis. As a clinical consequence wound healing
      capacity of mucous membranes is markedly impaired leading to ligneous
      conjunctivitis and several other manifestations. Here we report the molecular
      genetic and clinical findings on 23 new cases with severe hypoplasminogenaemia.
      Homozygous or compound-heterozygous mutations in the plasminogen (PLG) gene were
      found in 16 of 23 patients (70%), three of which were novel mutations reported
      here for the first time (C166Y, Y264S, IVS10-7T/G). Compared to 79 previously
      published cases, clinical manifestations of the current group of patients showed
      higher percentages of ligneous periodontitis, congenital hydrocephalus, and
      involvement of the female genital tract. In contrast, involvement of the
      gastrointestinal or urogenital tract was not observed in any of the cases.
      Patients originated to a large extent (61%) from Turkey and the Middle East, and
      showed a comparably frequent occurrence of consanguinity of affected families and
      a greater female to male ratio than was derived from previous reports in the
      literature. Individual treatment of ligneous conjunctivitis included topical
      plasminogen or heparin eye drops, topical or systemic fresh frozen plasma, and
      surgical removal of ligneous pseudomembranes, mostly with modest or transient
      efficacy. In conclusion, the present study underscores the broad range of
      clinical manifestations in PLG-deficient patients with a trend to regional
      differences. Transmission of genetic and clinical data to the recently
      established Plasminogen Deficiency Registry should help to determine the
      prevalence of the disease and to develop more efficient treatment strategies.

PMID- 21174001
TI  - High-shear- and-thrombin-inducible platelet adhesion and aggregation in patients
      undergoing percutaneous coronary intervention. Effects of unfractionated heparin
      versus bivalirudin.
AB  - Thrombin-generation and activation of platelets during percutaneous coronary
      intervention (PCI) play a key role for early thrombotic events. Heparin and
      bivalirudin are approved anticoagulants for PCI. We examined the specific effects
      of these anticoagulants on platelet adhesion and aggregation under high shear
      conditions, and the presence of excess thrombin. To simulate in vivo conditions
      that may precipitate a bleeding/thrombotic event, we added thrombin in vitro to
      blood samples from 89 stable patients who had been randomly assigned to receive
      heparin or bivalirudin for elective PCI and examined thrombin-inducible platelet
      adhesion and aggregation under high shear conditions. Platelet adhesion increased
      by 10% of baseline with heparin, but decreased by 20% with bivalirudin
      (p=0.0047). Thrombin-inducible platelet adhesion and size of aggregates was
      equally inhibited by heparin and bivalirudin. Thus, under high shear conditions
      and excessive thrombin generation as they occur in atherosclerotic vascular
      compartments and acute vascular syndromes, heparin and bivalirudin inhibit
      thrombin-induced platelet adhesion and aggregation to a similar extent, while
      they have opposite effects on platelet adhesion in the absence of thrombin.

PMID- 21174002
TI  - Regulation of the endothelial plasminogen activator system by fluvastatin. Role
      of Rho family proteins, actin polymerisation and p38 MAP kinase.
AB  - Statins are cholesterol-lowering drugs that exert pleiotropic effects which
      include changes in the plasminogen activation (PA) system of endothelial cells
      (EC). It was the objective of this study to investigate the signal transduction
      pathways by which statins increase the expression of tissue-type PA (t-PA) and
      decrease PA inhibitor type 1 (PAI-1) in human umbilical vein EC. Fluvastatin
      treatment increased t-PA expression more than 10-fold and reduced PAI-1
      expression up to five-fold. This effect was mimicked by geranylgeranyl
      transferase inhibition. The role of geranylgeranylated small G-proteins of the
      Rho family was assessed by adenovirus-mediated expression of dominant negative
      (DN) RhoA, Cdc42 and Rac1 and by siRNA-mediated suppression of these proteins. DN
      Cdc42 and DN-Rac1, as well as siRNA for Cdc42, increased t-PA expression, while
      DN-RhoA and DN-Rac1 decreased PAI-1 expression. Latrunculin B, an inhibitor of
      actin polymerisation, increased t-PA mRNA and reduced PAI-1 mRNA to the same
      extent as fluvastatin. Inhibition of p38, as well as p38alpha or p38beta siRNA,
      reversed the effects of fluvastatin on t-PA expression. Treatment with p38beta
      siRNA partially reversed the effect of fluvastatin on PAI-1, whereas p38alpha
      siRNA had no significant effect. Inhibition of jun kinase reduced basal and
      fluvastatin-induced t-PA expression to the same extent and increased PAI-1.
      MEK/ERK inhibition had no effect. In human EC, the fluvastatin-induced increase
      in t-PA is mediated by Cdc42 and, as with t-PA induced by inhibition of actin
      polymerisation, requires activation of p38MAP kinase. The mechanisms by which
      fluvastatin treatment reduces PAI-1 are different from those that increase t-PA.

PMID- 21174003
TI  - Inhibition of von Willebrand factor by ARC1779 in patients with acute thrombotic
      thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) can cause severe organ damage due to
      enhanced platelet aggregation by ultra-large von Willebrand factor (VWF)
      multimers. Thus inhibition of VWF by the anti-VWF ARC1779 might potentially be
      beneficial for TTP patients. This prospective trial tested the safety,
      pharmacokinetics and pharmacodynamics of the anti-VWF aptamer ARC1779 added to
      plasma exchange therapy (PEX) in patients with acute TTP. Seven patients received
      bolus primed continuous i.v. infusions of ARC1779 (1-2 MUg/kg/min) in addition to
      PEX until remission of TTP was induced or for 14 days. Mean steady state ARC1779
      plasma concentrations of 9.9 MUg/ml reduced VWF activity to 5% (mean baseline
      activity was 125% in TTP patients compared to a reference plasma). PEX reduced
      ARC1779 levels by 50%, but steady state concentrations were restored rapidly with
      a mini-bolus. After discontinuation of PEX, ARC1779 alone further increased
      platelet counts in one patient. Stopping ARC1779 was associated with an immediate
      drop of platelet counts in this patient. This suggests that ARC1779 can block the
      progression of TTP in patients with severe ADAMTS13 is deficiency. ARC1779 was
      generally well tolerated without any signs of bleeding. Pharmacokinetics and
      pharmacodynamics of ARC1779 were well predictable and in agreement with those
      observed in a previous trial with healthy volunteers. Based on its mechanism of
      action and the observed effect on platelet counts, ARC1779 used as an adjunctive
      to PEX may help accelerate recovery from organ dysfunction.

PMID- 21174004
TI  - Degradation of the endothelial glycocalyx is associated with chylomicron leakage
      in mouse cremaster muscle microcirculation.
AB  - A thick endothelial glycocalyx contributes to the barrier function of vascular
      endothelium in macro- and microcirculation. We hypothesised in the current study
      that diet-induced hyperlipidaemia perturbs the glycocalyx, resulting in decreased
      dimensions of this layer and increased transendothelial lipoprotein leakage in
      capillaries. Glycocalyx thickness was measured in mouse cremaster muscle
      capillaries by intravital microscopy from the distance between flowing red blood
      cells and the endothelial surface. In control C57BL/6 mice on standard chow,
      glycocalyx thickness measured 0.58 +/- 0.01 (mean +/- SEM) MUm, and no
      lipoproteins were observed in the tissue. After three months administration of an
      either mild or severe high-fat / high-cholesterol diet (HFC) to C57BL/6 and ApoE3
      Leiden mice, circulating large lipoproteins appeared into the subendothelial
      space in an increasing proportion of cremaster capillaries, and these capillaries
      displayed reduced glycocalyx dimensions of 0.40 +/- 0.02 and 0.30 +/- 0.01 MUm
      (C57BL/6 mice), and 0.37 +/- 0.01 and 0.28 +/- 0.01 MUm (ApoE3-Leiden mice),
      after the mild and severe HFC diet, respectively. The chylomicron nature of the
      accumulated lipoproteins was confirmed by observations of subendothelial
      deposition of DiI-labeled chylomicrons in capillaries after inducing acute
      glycocalyx degradation by heparitinase in normolipidaemic C57BL/6 mice. It is
      concluded that while under control conditions the endothelial glycocalyx
      contributes to the vascular barrier against transvascular lipoprotein leakage in
      the microcirculation, diet-induced hyperlipidaemia reduces the thickness of the
      glycocalyx, thereby facilitating leakage of chylomicrons across the capillary
      wall.

PMID- 21174005
TI  - Pre-analytical and analytical issues in the analysis of blood microparticles.
AB  - Results of plasma microparticles (MPs) measurements reported in the literature
      vary widely. This is clearly not only related to the lack of well-standardised MP
      assays, but also to variations in pre-analytical conditions. In this review we
      will discuss the pre-analytical variables related to plasma and MP preparation
      which may affect MP analysis. Additionally we will address several analytical
      issues in commonly used MP assays and briefly discuss some novel approaches for
      the detection and characterisation of MPs. Ideally MP measurements should be
      performed in plasma, freshly prepared directly after blood withdrawal. As
      platelet contamination seems to be one of the major pre-analytical problems in
      processing plasma for MP measurement, the use of platelet-free plasma may be
      preferred. When frozen-thawed plasma is used, especially PMP and annexinV
      positive MP counts should be interpreted with caution. When flow cytometry is
      chosen as a method for quantification of MPs, some analytical conditions should
      be standardised, e.g. settings of the flow cytometer, quality of the antibodies,
      and use of counting beads. Fluorescence-nanoparticle tracking analysis and atomic
      force microscopy can accurately count nanosized MPs, but unfortunately the
      operational procedures of both methods are still time consuming and they give no
      information on the functional properties of MPs. The MP-TF activity assay
      provides information on MPs carrying active TF, regardless of their parental
      origin. Ultimately, standardisation of pre-analytical procedures and the
      introduction of reliable and rapid methods for the measurement of MPs are
      urgently needed to facilitate their use as biomarker in the pathophysiology of
      diseases.

PMID- 21174006
TI  - The natural tissue plasminogen activator inhibitor neuroserpin and acute
      ischaemic stroke outcome.
AB  - Neuroserpin is a brain-derived natural inhibitor of tissue plasminogen activator
      (tPA) that has shown neuroprotective effects in animal models of brain ischaemia.
      Our aim was to investigate the association of neuroserpin levels in blood with
      functional outcome in patients with acute ischaemic stroke. Due to the potential
      effect of tPA treatment interfering on neuroserpin levels, we studied two
      different cohorts: 129 patients not treated with tPA and 80 patients treated with
      intravenous tPA within 3 hours (h) from symptoms onset. Neuroserpin levels were
      measured by ELISA. Good functional outcome at three months was defined as Rankin
      scale score <=2. In the two cohorts, serum neuroserpin levels on admission were
      significantly higher than at 24 h, 72 h and in healthy subjects. In non tPA
      treated patients, neuroserpin levels decrease at 24 h, but not levels at
      baseline, were associated with good outcome (for each quartile decrease, adjusted
      odds ratio [OR] 15.0; 95% confidence interval [CI], 3.5 to 66). In the tPA
      treated cohort, high neuroserpin levels before tPA bolus had the stronger effect
      on favourable outcome (for each quartile, OR 13.5; 95%CI, 3.9 to 47).
      Furthermore, for each quartile in neuroserpin levels before tPA bolus there was a
      80% (95%CI, 48 to 92) reduction in the probability of subsequent parenchymal
      haematoma. In summary, high serum neuroserpin levels before intravenous tPA and
      neuroserpin levels decrease at 24 h after ischaemic stroke, independently of tPA
      treatment, are associated with good functional outcome. These findings support
      the concept that neuroserpin might play an important role during cerebral
      ischaemia.

PMID- 21174007
TI  - Association between gamma' fibrinogen levels and inflammation.
AB  - The gamma' fibrinogen isoform produces clots that are stiffer and more resistant
      to breakdown than the more common fibrinogen isoform, gammaA. Increased levels of
      gamma' fibrinogen are associated with several forms of cardiovascular disease.
      The purpose of this cross-sectional study was to investigate the relationship
      between gamma' fibrinogen, an emerging risk factor for cardiovascular disease,
      and inflammatory markers in subjects with a chronic inflammatory state. The 284
      subjects for this study came from the Periodontitis And Vascular Events (PAVE)
      study, and gamma' fibrinogen and total fibrinogen in plasma were measured by
      ELISA. Information on patient demographics and health status, as well as levels
      of C-reactive protein (CRP), an inflammatory marker, have previously been
      collected for this study. The mean (SE) gamma' fibrinogen level in the subjects
      was 0.622 (0.017) mg/ml. Levels of gamma' fibrinogen were correlated with CRP (p
      = 0.006), with a one unit increase in CRP associated with a 1.9% increase in
      gamma' fibrinogen, after adjustment for potential confounders. Total fibrinogen
      was not correlated with gamma' fibrinogen in these subjects. The number of dental
      sites with evidence of tissue inflammation was also significantly associated with
      gamma' fibrinogen levels. These results provide an important step in the
      evolution of gamma' fibrinogen not only as a general risk factor for
      cardiovascular disease, but as a potentially useful biomarker for assessing a
      patient's inflammatory state and associated cardiovascular disease risk.

PMID- 21174008
TI  - Venous thromboembolism and bleeding after total knee and hip arthroplasty.
      Findings from the Spanish National Discharge Database.
AB  - The impact of venous thromboembolism (VTE) and bleeding in patients undergoing
      major joint surgery has not been thoroughly studied. The Spanish National
      Discharge Database during the years 2005-2006 was used to assess the frequency
      and clinical impact of VTE and bleeding after elective total knee (TKA) or hip
      (THA) arthroplasty. Of 58,037 patients undergoing TKA, 0.18% (95% confidence
      interval [CI]: 0.15-0.22) were diagnosed with pulmonary embolism (PE), 0.57% (95%
      CI: 0.51-0.63) with deep-vein thrombosis (DVT), 1.20% (95% CI: 1.12-1.30) had
      bleeding complications, and 0.09% (95% CI: 0.07-0.12) died. Of 54 patients who
      died, 20.4% (95% CI: 10.7-35.4) had been diagnosed with PE, 3.70% (95% CI: 0.63
      11.7) with DVT, and 13.0% (95% CI: 5.67-25.6) had bled. Of 31,769 patients
      undergoing elective THA, 0.23% (95% CI: 0.18-0.29) were diagnosed with PE, 0.44%
      (95% CI: 0.37-0.52) with DVT, 1.21% (95% CI: 1.10-1.34) bled, and 0.16% (95% CI:
      0.12-0.21) died. Of 52 patients who died, 13.5% (95% CI: 6.08-24.8) had been
      diagnosed with PE, and 9.61% (95% CI: 3.52-21.3) had bled. On multivariable
      analysis, PE (odds ratio [OR]: 157; 95% CI: 75-328), DVT (OR: 6.3; 95% CI: 1.5
      27) and bleeding (OR: 8.5; 95% CI: 3.6-20) were independent predictors for death
      after TKA. After THA, only PE (OR: 65; 95% CI: 26-160) and bleeding (OR: 6.4; 95%
      CI: 2.3-17) predicted the risk for death. Bleeding, DVT, and PE, arising after
      TKA were all independent predictors for death. Their increase in risk was,
      however, substantially higher for PE. After THA, only PE and bleeding
      independently predicted death.

PMID- 21174010
TI  - Navigating practice and academic change in collaborative partnership with a
      community advisory board.
AB  - University-based allied health programs must prepare entry-level professionals
      for a continually-evolving practice landscape. Health care education must
      demonstrate relevance to community needs in an environment of diminishing
      resources and increased scrutiny from governmental and accreditation bodies.
      Diverse perspectives, insights, and strategic counsel are needed to meet these
      challenges. Strategies associated with the development and functions of corporate
      and non-profit boards were used to tailor a community advisory board for a
      dietetics program at a public university. Over a 4-year period, this new board
      established an annual scholarship conference, funded an endowed scholarship,
      organized a student mentorship program, and secured new program equipment. The
      board played a pivotal role in development of and securing administrative
      approval for the establishment of a Nutrition Center for research, innovative
      practice, and service learning. In a recent accreditation site visit report, the
      role of the advisory board was cited as helping to meet education standards. An
      active advisory board can support strategic program innovation, resource
      development and help prepare health professionals for 21st century practice. The
      change-oriented, creative approach described can serve as a model for
      professional education programs seeking to engage the community in the success of
      their students.

PMID- 21174009
TI  - CC and CXC chemokines are pivotal mediators of cerebral injury in ischaemic
      stroke.
AB  - The definition of ischaemic stroke has been recently updated as an acute episode
      of neurological dysfunction caused by focal brain, spinal cord, or retinal
      ischaemia in the presence of a cerebral infarction. This "tissular" definition
      has highlighted the importance of pathophysiological processes underlying
      cerebral damage. In particular, post- ischaemic inflammation in the brain and in
      the blood stream could influence crucial steps of the tissue injury/repair
      cascade. CC and CXC chemokines orchestrate the inflammatory response in
      atherosclerotic plaque vulnerability and cerebral infarction. These molecules
      exert their activities through the binding to selective transmembrane receptors.
      CC and CXC chemokines modulate crucial processes (such as inflammatory cell
      recruitment and activation, neuronal survival, neoangiogenesis). On the other
      hand, CXC chemokines could also modulate stem cell homing, thus favouring tissue
      repair. Given this evidence, both CC and CXC chemokines could represent promising
      therapeutic targets in primary and secondary prevention of ischaemic stroke. Only
      preliminary studies have been performed investigating treatments with selective
      chemokine agonists/antagonists. In this review, we will update evidence on the
      role and the potential therapeutic strategies targeting CC and CXC chemokines in
      the pathophysiology of ischaemic stroke.

PMID- 21174011
TI  - A model minority faculty fellowship program: enhancing minority faculty in health
      professions and reducing inequity in health services.
AB  - Northern Arizona University (NAU), College of Health and Human Services model
      Minority Faculty Fellowship Program (MFFP) supports a minority faculty member and
      strengthens the College without adding to the workload or placing additional
      strain on an already limited budget. In 2003, the College was awarded a MFFP
      through the U.S. Department of Health, Health Resources and Services
      Administration. The College received a second Fellowship in 2008, the only one
      funded in the country. This three-year Fellowship is aimed at providing minority
      individuals with the training and skills necessary to flourish in a tenure-track
      position. There is a shortage of minority faculty in the health professions.
      Northern Arizona University and the surrounding communities have diverse
      populations nonetheless, only a very small percentage of faculty at the
      University are from diverse backgrounds. Success of the NAU, MFFP is largely due
      to our ability to draw upon existing structures including the University mission
      and institutional commitment to serving Native Americans, as well as the
      promotion and tenure process, faculty support programs, and a long-term
      relationship with the John and Sophie Ottens Foundation. The progress of the
      current NAU fellowship can also be attributed to the first Fellow's engagement
      with her contemporary.

PMID- 21174012
TI  - Information literacy: are final-year medical radiation science students on the
      pathway to success?
AB  - It is necessary for Medical Radiation Science (MRS) students to become
      information literate in order to interact with and thrive in the professional
      health care arena. All health care professionals require information literacy
      (IL) skills to be independent learners and critical thinkers. To achieve this,
      effective search and evaluation methods must be cultivated in students. Twenty
      eight final year MRS students participated in a 30-minute digitally recorded
      interview regarding their knowledge of information sources, where they locate
      information, and how they evaluate these sources. Constant comparative analysis
      via grounded theory was used to thematise the data. A conceptual framework was
      developed demonstrating the link between the key concepts of convenience,
      confidence and competence. The impact of the internet on the IL skills of
      students has been profound, due mainly to convenience. Most students had little
      confidence in their IL skills, however there were still some students who were
      confident with their skills and were competent who still preferred to access
      information sources that were convenient because there was nothing preventing
      them from doing so. By identifying problem areas, educators can redesign
      curricula around the strengths and weaknesses of students' IL skills, thus
      promoting lifelong learning and using electronic based learning to its full
      potential.

PMID- 21174013
TI  - A rural-urban comparison of allied health professionals' average hourly wage.
AB  - Nationwide, demand for allied health services is projected to grow significantly
      in the next several decades, and there is evidence that allied health shortages
      already exist in many states. Given the longstanding history of health
      professional shortages in rural areas, the existing and impending shortages in
      allied health professions may be particularly acute in these areas. To assess
      whether rural areas are potentially at a recruiting disadvantage because of
      relative wages, this report uses data from the Bureau of Labor Statistics to
      describe the extent to which rural-urban differentials exist in wages for eight
      allied health professions, focusing on professions that are both likely to be
      found in rural communities and have adequate data to support hourly wage
      estimates. Overall the data show that the national average wage of each of the
      eight allied health professions is higher in metropolitan than nonmetropolitan
      areas. On average, the unadjusted rural hourly wage is 10.3% less than the urban
      wage, although the extent of the difference varies by profession and by
      geographic area. Adjustment for the cost of living narrows the discrepancy, but
      does not eliminate it. It is likely that rural providers in areas with the
      greatest wage discrepancies find it more difficult to recruit allied health
      professionals, but the extent to which this is the case needs to be assessed
      through further research with data on workforce vacancy rates.

PMID- 21174015
TI  - Tolle lege in the context of an inch wide and a mile deep.

PMID- 21174014
TI  - Pedagogical tools to develop clinical reasoning: physical therapy students'
      perspective.
AB  - Physical therapy students' perspective about the development of clinical decision
      making ability was solicited to determine: 1) if actual clinical and academic
      learning experiences are consistent with student preferences; and 2) if actual
      academic learning experiences differ according to subject matter. Program
      representatives contacted physical therapy students via email with an embedded
      link to an on-line survey during their final clinical education experiences. Open
      ended and forced-choice items addressed reactions to learning experiences to
      develop clinical reasoning in academic and final clinical education experiences.
      Data were analyzed with frequency analysis, chi-square and correlations of survey
      items. Ninety-one respondents completed the survey, yielding a 13% response rate.
      The frequency of use of pedagogical tools was lower than the preferred use of the
      tools. Perceptions about clinical reasoning learning tools varied with course
      content. Course content corresponded to the type of pedagogical tool that
      students deemed essential for learning clinical reasoning. Participants appeared
      to experience and prefer more independence at the final clinical experience
      although they preferred considerable involvement by the clinical instructor.

PMID- 21174016
TI  - Rehabilitation in the context of HIV: an interprofessional multi-stakeholder
      process for curriculum development.
AB  - With longer survival, individuals living with human immunodeficiency virus (HIV)
      infection are facing a multitude of health-related challenges due to HIV, its
      associated concurrent health conditions, and treatments. Despite the need for
      rehabilitation, few rehabilitation professionals work with people living with
      HIV, with many feeling they lack adequate knowledge and skills to assess and
      treat this population. PURPOSE: We describe a national multi-stakeholder
      consultation used to inform the development of an interprofessional curriculum
      for rehabilitation professionals on HIV/AIDS. METHODS: We conducted a series of
      focus groups and key informant interviews (either in person or by telephone) with
      people living with HIV, rehabilitation professionals, physicians, curriculum
      experts, and other HIV stakeholders. Participants were asked to describe their
      perceived learning needs of rehabilitation professionals and to identify relevant
      content and delivery methods for a future interprofessional HIV/AIDS curriculum.
      RESULTS: Seven focus groups and 31 interviews with a total of 74 key informants
      were conducted, resulting in recommendations for content to include in HIV
      rehabilitation professional curricula and ways to deliver these curricula
      effectively. CONCLUSIONS: A national multi-stakeholder environmental scan was a
      useful preliminary step to inform the development of an interprofessional
      curriculum for rehabilitation professionals on HIV/AIDS. Recommendations serve as
      scaffold from which to build content and delivery of future curricula.

PMID- 21174017
TI  - Admission variables and academic success in the first year of the professional
      phase in a doctor of physical therapy program.
AB  - BACKGROUND: To date, there are no standard sets of admission criteria identifying
      an applicant's ability to succeed in an entry-level doctor of physical therapy
      (DPT) program. The purpose of this study was to determine if a relationship
      existed between preadmission variables and academic success, as measured by the
      physical therapy GPA in the basic sciences after the first professional year
      (PY1GPA). METHODS: The sample consisted of 63 students from three consecutive
      classes admitted to an entry-level DPT Program from fall 2002 through fall 2004.
      The preadmission variables included age, gender, degree status, pre-cumulative
      GPA, and prerequisite course GPA. The preadmission factors were correlated with
      the dependent variable of PYIGPA. In a second analysis, the resulting significant
      correlations (p < 0.05) were entered into a forward multiple regression analysis
      to determine the best predictors. RESULTS: The Spearman rho correlation
      coefficient indicated that the pre-cumulative GPA correlated positively to the
      PY1GPA in the basic sciences (r = 0.441, p < 0.01). After multiple regression
      analysis, it was revealed that pre-cumulative GPA and age accounted for 16.7 and
      3.9%, respectively, of the total variance (20.6%) in PY1GPA in the basic
      sciences. CONCLUSION: Although this study did not address academic success
      throughout the length of the professional academic program, the findings offer
      insight regarding students' initial academic performance. Gaining insight into
      students' performance at this early stage in their education may provide a
      greater understanding of their potential success throughout the graduate program.

PMID- 21174018
TI  - Impact of professional cultures on students' perceptions of interprofessionalism:
      some Norwegian experiences.
AB  - Professionals bring their own personal and professional culture, competence, and
      interaction styles to the work setting. This study explores how undergraduate
      students (n = 619) at five different professional qualification programs from two
      Norwegian university colleges perceived interprofession education and
      collaboration (interprofessionalism). The student groups were drawn from nursing,
      occupational therapy, physical therapy, biomedical laboratory science, and
      radiography. Another central aim was to investigate if professional cultures
      influence students' perceptions of interprofessionalism. The students completed a
      questionnaire about different aspects of interprofessionalism. A principal
      component analysis revealed three factors that provide some insight into how
      students perceive interprofessionalism. These factors were: 1) need for
      interprofessional collaboration, 2) value of interprofessional education, and 3)
      openness to interprofessionalism. The results also showed that the nursing
      student group valued interprofessional education more highly than the other
      student groups and was more open to interprofessionalism. On the other hand, the
      OT students were most aware of the need for interprofessional collaboration.

PMID- 21174019
TI  - Meeting Healthy People 2010 objective 1.7 in ASAHP programs.
AB  - A key objective of Healthy People 2010, a program of the U.S. Public Health
      Service, falls within the responsibility of member programs of the Association of
      Schools of Allied Health Professions (ASAHP). Objective 1.7 reads, "Increase the
      proportion of schools of medicine, schools of nursing and health professional
      training schools whose basic curriculum for health care providers includes the
      core competencies in health promotion and disease prevention." In light of the
      upcoming development of Healthy People 2020, this paper explores four specific
      topics related to Objective 1.7 outlined in the Clinical Prevention and
      Population Health Curriculum Framework, recommended by experts from a number of
      health disciplines, and whether or not ASAHP programs include these topics in
      their curricula. Survey data would indicate that many of the elements of the four
      topics are covered. A few key subjects, however, are not covered by all programs.
      For example, both immunization and preventive medicine are not included in
      required courses of a majority of the respondents. The development of health
      policy and understanding global health issues appear also to be lacking. Health
      professions educators are advised to consider the health promotion and disease
      prevention aspects of their curricula.

PMID- 21174020
TI  - Effectiveness of a computer-aided neuroanatomy program for entry-level physical
      therapy students: anatomy and clinical examination of the dorsal column-medial
      lemniscal system.
AB  - The purpose of this study was to determine if a computer-aided instruction
      learning module improves students' knowledge of the neuroanatomy/physiology and
      clinical examination of the dorsal column-medial lemniscal (DCML) system. Sixty
      one physical therapy students enrolled in a clinical neurology course in entry
      level PT educational programs at two universities participated in the study.
      Students from University-1 (U1;) had not had a previous neuroanatomy course,
      while students from University-2 (U2;) had taken a neuroanatomy course in the
      previous semester. Before and after working with the learning module, students
      took a paper-and-pencil test on the neuroanatomy/physiology and clinical
      examination of the DCML system. Kruskal-Wallis one-way ANOVA and Mann-Whitney
      tests were used to determine if differences existed between
      neuroanatomy/physiology examination scores and clinical examination scores before
      and after taking the learning module, and between student groups based on
      university attended. For students from U1, neuroanatomy/physiology post-test
      scores improved significantly over pre-test scores (p < 0.001), while post-test
      scores of students from U2 did not (p = 0.60). Neuroanatomy/physiology pre-test
      scores from U2 were significantly better than those from U1 (p < 0.001); there
      was no significant difference in post-test scores (p = 0.062). Clinical
      examination pre-test and post-test scores from U2 were significantly better than
      those from U1 (p < 0.001). Clinical examination post-test scores improved
      significantly from the pre-test scores for both U1 (p < 0.001) and U2 (p <
      0.001).

PMID- 21174021
TI  - Allied healthcare providers' role in screening for autism spectrum disorders.
AB  - There is evidence documenting that children are not being diagnosed with autism
      spectrum disorder (ASD) early enough. This study surveyed allied healthcare
      providers to determine whether these professionals had received training on the
      characteristics of ASD and ASD-specific screening strategies through their pre
      professional education or continuing education (CE). Additionally, participants
      were asked about their responsibility for screening children for ASD in their
      workplace and what would help them be better prepared to perform this type of
      screening. As a group, speech-language pathologists (SLPs) and occupational
      therapists (OTs) reported receiving more training on the characteristics of ASD
      and screening for ASD in both their pre-professional education and CE workshops
      than reported by the physical therapists (PTs) and physicians assistants (PAs).
      Overall, the SLPS, OTs, and PTs had attended more CE trainings to gain
      information on ASD than had PAs. All groups expressed an interest in receiving
      more information on ASD via on- or off-site trainings. These results provide
      initial support for allied healthcare providers to become more active in
      screening and referring children who present with symptoms of ASD. The study also
      highlights the need for educational institutions to provide future healthcare
      professionals with the skills to provide appropriate early identification
      services for children and families.

PMID- 21174022
TI  - From admission to graduation: the impact of gender on student academic success in
      respiratory therapy education.
AB  - Despite research in other allied health professions and medicine, the influence
      of gender on student performance in respiratory therapy (RT) academic programs
      and on the National Board for Respiratory Care (NBRC) examinations is unknown.
      Therefore, the purpose of this study was to identify the impact of gender on
      student academic performance from admission to graduation and to determine
      whether gender differences affected student success on the NBRC examinations.
      This study consisted of a retrospective analysis of 91 female and 22 male
      graduates at a southeastern U.S. university between 2003 and 2007. The variables
      of academic success included the students' entering GPA, exit GPA, and first
      attempt performance on the Certified Respiratory Therapy (CRT) examination and on
      the Written Registry for Respiratory Therapy (WRRT) examination. Independent
      sample t-test and paired sample t-test analyses at a level of significance of
      alpha = 0.05 were utilized. No significant gender differences were observed in
      the measures of students' entering GPA, exit GPA, or performance on scaled CRT
      and WRRT examinations (p > 0.05). When we compared entering GPAs and exit GPAs, a
      statistically significant difference was found (p < 0.05). Both male and female
      RT students had significantly higher exit GPAs than entering GPAs. The results of
      the study showed that gender plays no role in the academic success of RT
      students. When looking at the changes on academic success, we conclude that RT
      students work hard, as the graduation scores are higher than admission scores.

PMID- 21174023
TI  - Healthcare students' e-literacy skills.
AB  - To be critical healthcare consumers, patients must learn self-management skills
      and become active participants in knowledge management and exchange. eHealth
      literacy is considered critical to the development of these self-management
      skills. The World Health Organization identifies five core competencies required
      of all healthcare providers working with persons with chronic conditions, and
      this paper focuses on the fourth--the ability to employ information and
      communication technology. To supplement our literature-based argument, we also
      present findings from a class of first-year masters-level occupational therapy
      students asked to complete an existing standardized e-health literacy survey,
      eHEALS, as a learning activity. The eHEALS revealed that students reported
      confidence in their ability to critically appraise internet information but were
      not confident enough in those skills to use the information to make decisions
      without consulting a healthcare provider. It appeared that the students were not
      yet fully immersed in their role of healthcare professional and seemed to move
      between the roles of healthcare provider and healthcare recipient as they
      reflected on the class' answers to the eHEALS assessment. Evaluation of eHealth
      literacy is complex and needs to consider the multiple roles assumed by those
      whose knowledge is being assessed.

PMID- 21174024
TI  - Interprofessional education programs today: surveying model programs in the U.S.
      Introduction.
AB  - The challenges associated with interprofessional education (IPE) are well known
      to any of us who have attempted to implement a new IPE program, course, or
      curriculum. A scan of the IPE literature from the past decade reveals a host of
      documented barriers to IPE implementation, from a lack of funding and
      administrative support to the inability to manipulate the rigid schedules of
      multiple professional degree programs. Even an attitudinal barrier, such as a
      lack of respect for another profession, may present a seemingly insurmountable
      obstacle. Despite these inherent complications, however, there are a number of
      programs in the United States that have successfully negotiated a path to IPE.
      These programs have pioneered creative ways to integrate IPE into their current
      curricula and programs, through a process of careful interprofessional teamwork
      within their respective institutional systems. This e-supplement offers an
      intriguing glimpse into some of the most comprehensive and exceptional IPE
      programs that are currently underway in the United States.

PMID- 21174025
TI  - Jefferson InterProfessional Education Center, Thomas Jefferson University.
AB  - Thomas Jefferson University initiated the Jefferson InterProfessional Education
      Center in early 2007. The Center facilitates many diverse student and faculty
      projects on interprofessional education yearly. Faculty development programs
      include, most recently, the second Jefferson Interprofessional Education
      conference, IPE scholarly lecture series, an IPE and care practicum, and multiple
      lecture/discussions to select faculty/administrative groups. At present, there is
      no external funding for any of the programs. The Health Mentor Program is one of
      the major student programs. It is a required two-year longitudinal
      interprofessional chronic illness program for all medical, nursing, occupational
      therapy, physical therapy, pharmacy and couples and family therapy students. It
      began in the fall of 2007 and is integrated into existing coursework in each of
      the participating disciplines.

PMID- 21174026
TI  - Saint Louis University Interprofessional Education Program.
AB  - Saint Louis University's Interprofessional Education Program (SLU-IPE) started
      with interprofessional courses throughout the curricula of the health
      professional programs of the Edward and Margaret Doisy College of Health Sciences
      and the School of Nursing. The goal of SLU-IPE is to prepare graduates for
      interprofessional patient/client-centered practice, effective and efficient
      delivery of health care services, and advocacy for improvement of health and
      health services. In developing the SLU-IPE curriculum, faculty adopted the
      premise that IPE is needed to prepare graduates for interprofessional practice,
      which significantly improves the likelihood of patients attaining optimal health
      care outcomes. Other premises include that learning experiences, both didactic
      and practical, should be interactive and that interprofessional learning
      activities should occur throughout the length of the educational programs.

PMID- 21174027
TI  - Rosalind Franklin University of Medicine and Science.
AB  - Rosalind Franklin University of Medicine and Science, located in North Chicago,
      Illinois, is a private, health professions university educating health and
      biomedical professionals in an innovative, student-centered environment. The
      University is composed of 4 colleges: the Chicago Medical School, the Scholl
      College of Podiatric Medicine, the College of Health Professions, and the School
      of Graduate and Postdoctoral Studies. At Rosalind Franklin University, we are
      committed to Interprofessional Education as stated in our vision and introduced
      through our first-year Interprofessional experience for all incoming students.

PMID- 21174028
TI  - Creating Collaborative Care (C3), Medical University of South Carolina.
AB  - The Creating Collaborative Care (C3) program is a university-wide, comprehensive
      interprofessional education initiative. It was developed as the university's
      Quality Enhancement Plan for reaffirmation of accreditation by the Southern
      Association of Colleges and Schools. Four student learning goals guide the
      initiative and development of its components. C3 activities include required
      academic (including health care simulation experiences), co-curricular, and
      faculty development. C3 was established in 2007, though some activities pre-date
      its establishment. Funding is primarily from the university, though small grants
      have supported development of a few activities. Since aspects of the program are
      required, students receive academic credit for participation; for co-curricular
      activities, they do not. The C3 program extends over the course of a student's
      education at MUSC.

PMID- 21174029
TI  - Office of Interdisciplinary Health Studies Education, East Carolina university.
AB  - The Office of Interdisciplinary Health Sciences Education resides
      organizationally within East Carolina University (ECU), Division of Health
      Sciences; ECU established this office in 1999. The mission of the office is
      fivefold: 1. promote the expansion of interdisciplinary training within and
      between Health Sciences and other health-related programs on campus; 2. promote
      innovative research opportunities across disciplines, in particular, projects
      regarding interdisciplinary health sciences education; 3. serve as a
      clearinghouse for information relative to existing and planned interdisciplinary
      activities and projects within the Division; 4. collaborate with units, and
      communities in establishing community partnerships for interdisciplinary rural
      health training; and 5. identify core curricular content across health-related
      disciplines, minimizing curricular redundancy while promoting interdisciplinary
      collaboration.

PMID- 21174030
TI  - The Macy Interprofessional Collaborative Project, the University of Washington.
AB  - Through multiyear grants awarded by the Macy and Hearst Foundations, the Macy
      Interprofessional Collaborative is in year two of developing a simulation-based,
      team training program. The program's overall goal is to improve the delivery of
      safe, high quality care by increasing interprofessional team communication. The
      training will be validated and incorporated into existing, credit-based curricula
      in health sciences schools and will include both a faculty development component
      and an exportable web-based toolkit for adaptation of the training at other
      health science institutions.

PMID- 21174031
TI  - InterProfessional Education Collaborative (IPEC), The University of New England.
AB  - The University of New England includes more than a dozen health or health related
      programs within its colleges of Health Professions, Osteopathic Medicine,
      Pharmacy, Arts and Sciences, School of Public Health, and a soon to be founded
      College of Dental Medicine. For more than a decade, the Westbrook College of
      Health Professions has integrated interprofessional education into its programs.
      Early successes included extra-curricular programming such as seminars, symposia,
      a film series, research and scholarship days, interprofessional grand rounds, and
      cultural immersion experiences.

PMID- 21174032
TI  - Collaborative Care for Older Adults (COCOA), Palmer College of Chiropractic.
AB  - Integrative medicine (IM) is a subset of interprofessional health care that seeks
      to join the knowledge and practices of various allopathic and complementary and
      alternative medicine disciplines in an attempt to offer cost-effective and
      clinically significant healthcare options for persons with acute or chronic
      illnesses. Although touted as a means for improving health outcomes and patient
      satisfaction while possibly lowering costs, further scientific evidence regarding
      the utility of IM approaches to health services delivery is needed. Collaborative
      Care for Older Adults (COCOA) is a chiropractic demonstration project that brings
      together an interdisciplinary team of researchers and clinicians from the Palmer
      Center for Chiropractic Research, Genesis Quad Cities Family Practice Residency,
      The University of Iowa, and Thomas Jefferson University to study the impact of a
      model of interprofessional education on geriatric health care. The Health
      Resources and Services Administration funded COCOA in 2009 to further develop and
      assess a patient-centered care model for the treatment of low back pain in older
      adults that uses a team-based approach between medical doctors and doctors of
      chiropractic.

PMID- 21174033
TI  - Interprofessional Education program, Western University of Health Sciences.
AB  - In January 2010, Western University of Health Sciences launched the first phase
      of its Interprofessional Education (IPE) program. Our mission is to produce
      humanistic healthcare professionals who practice collaborative patient-centered
      care. The university wide comprehensive IPE program model includes didactic,
      experiential and clinical care phases. The first phase of the IPE program,
      didactic, rolled out during the 2009-2010 academic year. While the data from the
      first year is still being evaluated, initial indicators reveal the launching of
      the first year of the program was a success. Assessment is and will continue to
      be an essential aspect of every phase of the IPE model.

PMID- 21174034
TI  - Interprofessional Forum and Competition, University of Pittsburgh.
AB  - Initiated in fall 2008, the annual Interprofessional Forum introduces the theme
      of interprofessional collaboration to an audience of approximately 600 first-year
      students drawn from the University of Pittsburgh Schools of the Health Sciences
      (dental medicine, health and rehabilitation sciences, medicine, nursing,
      pharmacy, and public health). The required 2-hour program targets the following
      learning outcomes and goals: Illustrate the areas of expertise of various health
      professionals who provide patient care; Explore the importance of teamwork among
      health care providers from the patient's perspective, as well as to provide
      "complete" care and optimized patient functionality and quality of life; and
      Describe how health professions education programs are addressing
      interprofessional team skills and practice models.

PMID- 21174035
TI  - 1Health, the Center for Interprofessional Education, the University of Minnesota.
AB  - The Center for Interprofessional Education within the Academic Health Center at
      the University of Minnesota is launching a new initiative called 1Health. 1Health
      requires health professional students to participate in courses and/or
      experiences to achieve competencies set by the Academic Health Center prior to
      graduation. This new initiative will launch with Phase I in the fall of 2010 and
      will include all beginning health professional students enrolled in participating
      programs.

PMID- 21174036
TI  - Comments on a special issue of the Journal of Allied Health.
AB  - The 2010 Annual Conference of the Association of Schools of Allied Health
      Professions (ASAHP) will be conducted in Charlotte, North Carolina, on October 20
      22. The theme for this event is "Through an Interdisciplinary Looking Glass:
      Achieving Quality Outcomes through Research, Education, and Practice." Although
      the terms interdisciplinary and interprofessional differ from one another, they
      are close enough to justify an intent to have copies of this special issue of the
      Journal prepared and distributed in advance of the conference.

PMID- 21174037
TI  - Special issue on interprofessional education and care.
AB  - It's been 12 years since the Journal published its last special themed issue (see
      Winter 1998, volume 27, no. 1), focused on the World Congress held in Telford,
      UK, in July 1997. Since that time, there have been a number of subjects that
      probably warranted special attention, but were not addressed. For that, you can
      blame one of the Editors of this special issue, who served as Journal Editor
      during that 10-year period. The topic of interprofessional education (IPE) and
      care (IPC) is one such theme that warrants our attention at this time.
      Interprofessional approaches by now have received not only increased attention in
      the United States, but attention from across the globe. This makes the task of
      putting together this issue both easy but, at the same time, a bit daunting. Easy
      in the sense that there is no lack of reports, programs, and efforts at
      implementing both IPE and IPC from which to choose. Daunting for the same reason:
      Which are the ones that deserve special attention? What major initiative have we
      missed?

PMID- 21174038
TI  - The ascent of Mt. Everest.
AB  - Earlier this Spring, I reread the account of the 1924 attempt of Mallory and
      Irvine to summit the highest mountain in the world, Mt. Everest. Apart from the
      recurring mystery of whether the English climbers actually achieved their goal
      before disappearing on the upper reaches of the mountain, what emerged for me
      were the many failed attempts (including two earlier ones of their own) before
      the summit was finally conquered by Sir Edmund Hillary and Tenzing Norgay in
      1953. This put me in mind of the current efforts to once more try to implement
      the concept of interprofessional education and teamwork in the solution to our
      many problems in delivering quality health care to all our citizens. The
      recurring calls in every recent report on health care by the Institute of
      Medicine and other national groups for greater implementation of collaborative
      practice models and interprofessional education (IPE) have reawakened the hope
      that this time, at last, we might succeed. But looming over the horizon, like the
      storm clouds constantly shrouding the summit of Everest, are the oft-dashed hopes
      that resurfaced throughout the last century; such that the course of IPE and IPP
      (interprofessional practice) often has been described as one of successive cycles
      of "boom and bust."

PMID- 21174039
TI  - A WHO report: framework for action on interprofessional education and
      collaborative practice.
AB  - This article summarizes the key features of the World Health Organization's
      Framework for Action on Interprofessional Education and Collaborative Practice.
      The Framework is a call for action to policy-makers, decision-makers, educators,
      health workers, community leaders, and global health advocates to move toward
      embedding interprofessional education and collaborative practice in all of the
      services they deliver.

PMID- 21174040
TI  - Synthesis of systematic review evidence of interprofessional education.
AB  - Interprofessional education (IPE) continues to be a central focus within health
      care and research spheres. As a result, there is a sustained interest in
      understanding its overall effects on learners, professions, organizations, and
      patients. Systematic reviews are instrumental in assessing evidence and informing
      disciplinary fields about the effects of interventions and providing direction
      for future activity and research. This paper provides a synthesis and critical
      appraisal of the evidence for IPE contained in the small, but growing, systematic
      review literature. Six IPE reviews were located. In general, the reviews shared
      similar definitions of IPE and similar methodological approaches to their
      inclusion of studies. Findings from the synthesis indicated that IPE varied in
      terms of content, duration, and professional participation. The synthesis also
      indicated that studies that evaluated this form of education were of variable
      quality and captured a range of different outcomes-from reports of learner
      satisfaction to changes in the delivery of care. While a number of methodological
      problems were found, in general the synthesis indicated that IPE delivered in a
      variety of settings was generally well received by learners and enabled the
      acquisition of knowledge and skills necessary for collaborative working. Some
      evidence was also found that IPE can improve the delivery of services and make a
      positive impact on care. The paper goes on to discuss the synthesis findings in
      relation to the most recent IPE literature and also offers a series of
      suggestions for future directions.

PMID- 21174041
TI  - American Interprofessional Health Collaborative: historical roots and
      organizational beginnings.
AB  - This article describes the emergence of the American Interprofessional Health
      Collaborative to rebuild capacity for interprofessional education and care in the
      U.S. through an inclusive, evidence-based and open exchange of information and
      resources. Also described are the historical context and the national and
      international climate for its emergence.

PMID- 21174042
TI  - The Advisory Committee on Interdisciplinary Community-based Linkages and the
      federal role in advocating for interprofessional education.
AB  - This article reviews the background, structure, and role of the Advisory
      Committee on Interdisciplinary, Community-based Linkages (ACICBL) in the U.S.
      federal government. The ACICBL's annual reports have consistently addressed
      interdisciplinary education related to Title VII, Part D-Interdisciplinary,
      Community-based Linkages programs. The ACICBL is clearly a champion of
      interdisciplinary/interprofessional education (IPE). ACICBL recommendations since
      its first report in 2001 have emphasized the need for
      interdisciplinary/interprofessional initiatives to increase diversity, cultural
      competence, health disparities, the allied health workforce, the health workforce
      pipeline, faculty development, rural health workforce, and use of technology for
      the advancement of interdisciplinary health care. Its most recent report,
      focusing on the interdisciplinary/IPE of health professions students, faculty,
      and practitioners, made recommendations around interprofessional faculty
      development, interprofessional curriculum development, IPE competency
      development, program evaluation, technology standards, and accreditation
      standards.

PMID- 21174043
TI  - The status of interprofessional education in Canada.
AB  - This article describes the history and development of interprofessional education
      (IPE) in Canada from its conceptual beginnings in the 1960s to today. The status
      of IPE in Canada is viewed in relation to the broader international movements for
      IPE and collaborative healthcare. The current goals and principles of the
      Canadian Interprofessional Health Collaborative are reviewed, and the future of
      IPE is considered in light of these goals.

PMID- 21174044
TI  - Interprofessional education assessment and planning instrument for academic
      institutions.
AB  - This article describes the creation, development, and peer review of an
      instrument for the assessment and improvement of interprofessional health
      educational programs in public and private health educational institutions
      nationally and internationally. The self-assessment is constructed with
      consideration of the following domains: educational venues, educational
      evaluation, programmatic participation, institutional support, and faculty
      incentives. The interprofessional education assessment and planning instrument
      for academic institutions can be a major aide in helping national and
      international leaders promoting IPE as the method to prepare future health
      professionals.

PMID- 21174045
TI  - The art and science of interprofessional education.
AB  - Interprofessional education (IPE) is increasingly accepted as a core element of
      health professions education. Its primary function is to prepare health
      professions students to engage in and deliver interprofessional, team-based
      healthcare, with the ultimate goal of improving the health and well-being of
      patients and clients. This paper summarizes findings from 10 interviews with
      institutional leaders in the field. The goal was to discover core themes than
      contribute to the art and science of IPE. Thematic challenges and successes are
      reviewed, and recommendations are provided for further research and for those
      interested in developing or improving IPE in their own institutions.

PMID- 21174046
TI  - Technologies for interprofessional education: the interprofessional education
      distributed "e-Classroom-of-the-Future".
AB  - Communications strategies are central to the planning and execution of
      interprofessional education (IPE) programs. The diversity of telecommunications
      based tools and platforms available for IPE is rapidly expanding. Each tool and
      platform has a potentially important role to play. The selection, testing, and
      embedding of tools, such as social networking platforms, within education
      programs can be very challenging. The goal was to create, in Phoenix, a "command
      and-control" video conferencing center (the T-Health Amphitheater or Telehealth
      Amphitheater) in which tele-consultation patients, located physically at one of
      the affiliated tele-clinics around the state, could be presented electronically
      to interprofessional teams of faculty members from the University of Arizona
      Colleges of Medicine, Nursing, Pharmacy, and Public Health, as well as those from
      the allied health colleges of other universities in Arizona, for
      interprofessional team training in a virtual classroom setting. The T-Health
      video conferencing facility was designed and built. Early assessments show that
      its novel learning environment is student- and faculty-friendly. T-Health
      Amphitheater's pair of innovative visible social networking platforms (eStacksTM
      and eSwapsTM) may help break down some of the traditional communications barriers
      encountered in healthcare IPE and medical practices.

PMID- 21174047
TI  - Interprofessional ethics in rehabilitation: the dreamcatcher journey.
AB  - In 2003, we led a working conference on leadership in ethics education for
      physical therapy and occupational therapy entitled, "Dreamcatchers and the Common
      Good: Allied Health Leadership in Generational Health and Ethics." The institute
      brought together 25 leaders in ethics education in physical therapy and
      occupational therapy for a 3-day working conference of experts. In this paper, we
      discuss our work as part of an interdisciplinary community of ethics educators
      who have been grappling with ethics education in rehabilitation over the last 7
      years. We reflect on our collaborative work and then propose components of a
      moral foundation required for continued interprofessional dialogue and work.

PMID- 21174048
TI  - Is interprofessionality a threshold concept for education and health care
      practice?
AB  - Advocated for over the last decade, only recently has interprofessional education
      and practice been front and center in conversations in allied health. The wide
      acceptance of interprofessional education and practice, however, comes with its
      own set of unique issues. In fact, many people may purport to be
      interprofessional when they are acting in a manner inconsistent with it. The
      challenge of learning about and truly understanding interprofessionality is
      exemplified when pondering what constitutes a threshold concept. A threshold
      concept is a relatively new term in educational theory and relates to content or
      conceptual knowledge that can open up new ways of thinking. Collectively, this
      article presents our thinking on interprofessionlity as a threshold concept for
      interprofessional education and practice.

PMID- 21174049
TI  - Developing the International Society of Physical and Rehabilitation Medicine
      (ISPRM): following through.
AB  - In 2008 the International Society of Physical and Rehabilitation Medicine (ISPRM)
      started an initiative to systematically develop its capacity and its internal and
      external policy agenda. This paper sums up achievements that have been made with
      this ISPRM initiative as well as pending issues and strategies to address them.
      The paper treats the following: ISPRM's policy agenda in collaboration with the
      World Health Organization (WHO), research capacity in functioning and
      rehabilitation, ISPRM world conferences, relationships with regional societies of
      Physical and Rehabilitation Medicine (PRM), and ISPRM's membership and governance
      structure.

PMID- 21174050
TI  - Practical considerations for goal attainment scaling during rehabilitation
      following acquired brain injury.
AB  - OBJECTIVE: Goal attainment scaling represents a unique approach to identifying
      and quantifying individualized, meaningful treatment outcomes, and its use in the
      rehabilitation medicine setting is increasing. The aim of this paper is to
      discuss the available literature for goal attainment scaling in patients with
      acquired brain injury, in terms of its advantages, disadvantages and practical
      application, including examples of goal setting and scaling.

PMID- 21174052
TI  - Post polio syndrome: fatigued patients a specific subgroup?
AB  - OBJECTIVES: To examine the characteristics of fatigued and non-fatigued post
      polio patients and to define potential subgroups across the fatigue continuum.
      DESIGN: Multi-centre study. SUBJECTS: A total of 143 post-polio patients were
      subdivided on the basis of percentile distribution into a fatigue group, a
      intermediate group, and a non-fatigue group, using the Multi Fatigue Inventory 20
      general fatigue ratings. METHODS: Data on background, quality of life, fatigue
      and pain were collected. Descriptive statistics and correlations in each group
      and analysis of variance and chi2 for group comparisons were performed. Non
      linear regressions were employed to evaluate differences in the strength of
      associations between physical and mental fatigue, on the one hand, and vitality
      on the other. RESULTS: The fatigued group was younger, had shorter polio
      duration, more pain, higher body mass index, lower quality of life and was more
      physically and mentally fatigued. A higher proportion of this group had
      contracted polio after 1956 and was under 65 years of age. Mental fatigue had a
      relatively higher explanatory value than physical fatigue for differences in
      vitality in the fatigued group, whereas reversed patterns were seen in the other
      groups. CONCLUSION: Fatigued post-polio patients can be considered as a subgroup.

PMID- 21174051
TI  - Rationale and design of a multicentre, double-blind, prospective, randomized,
      European and Canadian study: evaluating patient outcomes and costs of managing
      adults with post-stroke focal spasticity.
AB  - OBJECTIVE: This report describes the design of a study aiming to provide evidence
      for the extended use of botulinum toxin A in focal post-stroke upper and lower
      limb spasticity and to evaluate the impact of incorporating botulinum toxin
      treatment into the rehabilitation of patients with spasticity. DESIGN:
      International, prospective, randomized, double-blind, placebo-controlled study
      with an open-label extension. METHODS: Approximately 300 adults with a stroke
      occurring >= 3 months before screening, presenting with symptoms and signs of an
      upper motor neuron syndrome and focal spasticity-related functional impairment,
      were randomized to botulinum toxin (BOTOX(r), Allergan Inc.) + standard care or
      placebo + standard care. Study medication was administered at baseline and again
      at Week 12 if required, with follow-up to 52 weeks. The primary endpoint was the
      number of patients who achieved their investigator-rated principal active
      functional goal (as measured by Goal Attainment Scaling), at 10 weeks after the
      second injection (Weeks 22-34) or at the 24-week visit if no second injection was
      administered. Secondary endpoints included changes from baseline in level of goal
      achievement, health-related quality of life and resource utilization. CONCLUSION:
      Botulinum toxin A Economic Spasticity Trial (BEST) will provide information
      regarding clinical and cost-effectiveness of botulinum toxin + standard care vs
      standard care alone in patients with upper and/or lower limb post-stroke
      spasticity typically seen in clinical practice. TRIAL REGISTRATION:
      ClinicalTrials.gov number NCT-00549783.

PMID- 21174053
TI  - Do male and female patients with chronic musculoskeletal pain differ in their pre
      treatment expectations of rehabilitation outcome?
AB  - PURPOSE: To analyse differences between males and females in expectations about
      rehabilitation outcome. METHODS:  DESIGN: cross-sectional study. SETTING: a
      general rehabilitation centre. PATIENTS: n = 616, mean age 44 years, with chronic
      musculoskeletal pain, referred for multidisciplinary pain rehabilitation. All
      eligible patients in the period January 2005 to September 2009 were sent a
      questionnaire prior to or during the first two weeks of the treatment; the
      response was 630 out of 1105 (57%), of whom 14 patients did not give permission
      to use their data for research purposes. MAIN OUTCOME MEASURE: odds ratios.
      RESULTS: Odds ratios for 21 items from a list of 25 expectations were not
      significant, odds ratios for 3 expectations were lower than 2 and odds ratio for
      1 expectation was 4.0. Male patients were more likely than female patients to
      expect that the treatment would enable them to cope better with being a spouse
      and that the cause of their pain would be found. Female patients were more likely
      than male patients to expect that the treatment would enable them to better
      accept the fact that they could no longer do what they were able to do in the
      past, and that they would have fewer problems with household activities.
      CONCLUSION: There were no gender differences in pre-treatment expectations for 21
      of 25 possible expectations, small differences for 3 expectations and a strong,
      clinically important difference for 1 expectation: female patients were more
      likely than male patients to expect that they would have fewer problems with
      household activities.

PMID- 21174054
TI  - Goal attainment scaling and its relationship with standardized outcome measures:
      a commentary.

PMID- 21174055
TI  - Facial paresis after stroke and its impact on patients' facial movement and
      mental status.
AB  - OBJECTIVE: The aims of this study were: (i) to monitor changes in central facial
      paresis in patients with stroke after orofacial therapy, using functional scales
      and video analysis of the face; and (ii) to investigate correlations between
      changes in facial movement and mental function of patients after stroke. METHODS:
      A prospective blind randomized study of patients after stroke with facial
      paresis. The functional status of the experimental group of 50 cases treated with
      regulation orofacial therapy was compared with 49 control cases after 4 weeks of
      rehabilitation. RESULTS: There were changes in facial movement, evaluated with
      the House-Brackmann Grading System (HBDS), clinical range and two-dimensional
      video analysis of the distance between the paretic corner of the mouth and
      earlobe at rest and during smiling, were measured. Facial movement was found to
      be significantly better in the experimental group after orofacial therapy
      compared with the control group. Changes in mental status (depression observed
      using the Beck Depression Inventory (BDI-II) were significantly greater in the
      experimental group. There was a close correlation between the changes in facial
      movement and mental status according to Spearman's correlation coefficient.
      CONCLUSION: Orofacial therapy has a significant effect after 4 weeks of treatment
      on facial movement and mental state in patients with stroke. Based on the results
      in our study we can say that the improvements are a significantly better in the
      experimental group (Difference value) in the parameters HBGS, distance between
      the corner of the mouth and earlobe and BDI-II.

PMID- 21174056
TI  - Combined therapy with a thymidylate synthase-inhibiting vector and S-1 has
      effective antitumor activity against 5-FU-resistant tumors.
AB  - High levels of intratumoral thymidylate synthase (TS) expression are associated
      with resistance to 5-fluorourcil (5-FU). In order to establish a new treatment
      method for 5-FU-resistant tumors, the efficacy of gene therapy was investigated
      using an adenoviral vector expressing short hairpin RNA (shRNA) targeting TS. A
      replication-deficient recombinant adenoviral vector expressing shRNA targeting TS
      was constructed under the control of the human U6 promoter (Ad-shTS). Three 5-FU
      resistant cancer cell lines, DLD-1/5FU, KM12C/5FU and NUGC-3/5FU, were used.
      Transduction with Ad-shTS effectively downregulated TS expression in all three 5
      FU-resistant tumor cells. MTT assays demonstrated that treatment with Ad-shTS
      significantly inhibited the growth of all three 5-FU-resistant tumor cells.
      Furthermore, combined treatment with Ad-shTS and 5-FU demonstrated significantly
      greater inhibition of tumor cell growth in comparison to 5-FU treatment alone and
      Ad-shTS treatment alone. S-1, a combination of tegafur, gimeracil and oteracil
      potassium, was used for the 5-FU treatment by in vivo experiments. The combined
      treatment of Ad-shTS and S-1 was found to have the strongest antitumor effect
      against 5-FU-resistant DLD-1/5FU xenografts in nude mice in comparison to S-1
      treatment alone and Ad-shTS treatment alone. Furthermore, the apoptotic index in
      tumors treated with combined Ad-shTS and S-1 was significantly higher in
      comparison to that in tumors treated with S-1 alone and that in tumors treated
      with Ad-shTS alone. Consequently, the combined treatment of the TS-inhibiting
      adenoviral vector and S-1 has effective antitumor activity against 5-FU-resistant
      tumors.

PMID- 21174057
TI  - Protein kinase C-delta isoform mediates lysosome labilization in DNA damage
      induced apoptosis.
AB  - A lysosomal pathway, characterized by the partial rupture or labilization of
      lysosomal membranes (LLM) and cathepsin release into the cytosol, is evoked
      during the early events of 20-S-camptothecin lactone (CPT)-induced apoptosis in
      human cancer cells, including human histiocytic lymphoma U-937 cells. These
      lysosomal events begin rapidly and simultaneously with mitochondrial
      permeabilization and caspase activation within 3 h after drug treatment.
      Recently, in a comparative proteomics analysis performed on highly-enriched
      lysosomal extracts, we identified proteins whose translocation to lysosomes
      correlated with LLM induction after CPT treatment, including protein kinase C
      delta (PKC-delta). In this study, we show that the PKC-delta translocation to
      lysosomes is required for LLM, as silencing its expression with RNA interference
      or suppressing its activity with the inhibitor, rottlerin, prevents CPT-induced
      LLM. PKC-delta translocation to lysosomes is associated with lysosomal acidic
      sphingomyelinase (ASM) phosphorylation and activation, which in turn leads to an
      increase in ceramide (CER) content in lysosomes. The accumulation of endogenous
      CER in lysosomes is a critical event for CPT-induced LLM as suppressing PKC-delta
      or ASM activity reduces both the CPT-mediated CER generation in lysosomes and CPT
      induced LLM. These findings reveal a novel mechanism by which PKC-delta mediates
      ASM phosphorylation/activation and CER accumulation in lysosomes in CPT-induced
      LLM, rapidly activating the lysosomal pathway of apoptosis after CPT treatment.

PMID- 21174058
TI  - MicroRNA expression profiles in human colorectal cancers with liver metastases.
AB  - At present, a full understanding of the mechanisms by which colorectal cancer
      (CRC) distant metastases form is still beyond our reach because of the intricate
      regulation of gene expression. MicroRNAs (miRNAs) are shown to be involved in
      various human diseases including cancers through negative regulation of target
      gene expression at the post-transcriptional level. However, there are only a few
      studies on the roles of miRNA aberrations in liver metastasis of human colorectal
      cancer. To identify miRNA expression patterns associated with liver metastasis in
      human colorectal cancer, the miRNA expression profiles of colorectal cancer
      tissues with liver metastasis and their non-metastatic counterparts were studied
      using microRNA microarrays and further confirmed by quantitative RT-PCR. We show
      that 28 miRNAs are differentially expressed in the colorectal carcinomas with
      liver metastasis compared to the non-metastatic counterparts. Of these, 4 miRNAs
      including miR-150*, miR-125b-2*, miR-1179 and miR-139-3p were up-regulated in
      colorectal cancers with liver metastasis while the others were down-regulated.
      The target genes of selected deregulated miRNAs were predicted through
      bioinformatic techniques with two functional analyses, gene ontology and KEGG
      analysis, which showed that categories of high enrichment GOs and specific
      pathways targeted by dysregulated miRNAs were involved in liver metastasis during
      human colorectum carcinogenesis. Our results indicated that miRNAs are not only
      involved in carcinogenesis of colorectum, but may also participate in the
      progression such as with liver metastases in human colorectal cancers.

PMID- 21174059
TI  - Altered expression of imprinted genes in Wilms tumors.
AB  - Overexpression of insulin-like growth factor 2 (IGF2), an imprinted gene located
      on chromosome 11p15, has been reported as a characteristic feature in various
      embryonal tumors, including Wilms tumor (WT). Recent studies specified loss of
      imprinting (LOI) in a differential methylated region (DMR) of the IGF2/H19
      cluster or loss of heterozygosity (LOH), respectively, uniparental disomy (UPD)
      being responsible for this overexpression. However, the role of other imprinted
      genes in the genesis of WT is still unknown. In the current study, we analyzed
      transcriptional activity of the imprinted genes IGF2, H19, NNAT, DLK1, RTL1,
      MEG3, and MEST as well as the methylation status of the DMR of the IGF2/H19
      cluster in a panel of 32 WTs. Except for H19, we detected massive overexpression
      of all genes in the majority of WTs compared to normal renal tissue, which was
      most prominent for the paternally expressed genes IGF2, NNAT, and MEST.
      Alterations of the H19DMR were found in two-thirds of the WTs. Moreover, we have
      seen a strong correlation between the transcriptional activity of IGF2, NNAT and
      MEST and LOI/LOH of H19DMR, which was inverse for H19. Expression of DLK1, RTL1
      and MEG3 does not correlate with LOI/LOH of H19DMR. Altogether, our findings
      suggest that over-expression of imprinted genes is common in WTs and correlates
      at least for some imprinted genes with LOI of H19DMR. Thus, it may be speculated
      that alterations of the DNA modification machinery drive erroneous setting of
      methylation marks in imprinting regions throughout the genome, which leads to the
      concomitant activation of imprinted genes in blastomagenesis.

PMID- 21174060
TI  - RC-RNase-induced cell death in estrogen receptor positive breast tumors through
      down-regulation of Bcl-2 and estrogen receptor.
AB  - RC-RNase exerts anti-cancer effects on many tumors. However, the mechanisms by
      which RC-RNase induces cytotoxicity in different tumor cells are unclear.
      Currently, estrogen receptor (ER)-positive and negative breast tumors are treated
      with RC-RNase. Our data demonstrate that RC-RNase induces cell death on ER
      positive but not on ER-negative breast tumors. This study also shows that down
      regulation of ER and Bcl-2 is found on RC-RNase-treated ER-positive breast
      tumors. Additionally, Bcl-2 overxpression can prevent ER-positive breast tumors
      from cell death treated with RC-RNase. In summary, this study demonstrates that
      RC-RNase-induced cell death of ER-positive breast tumors is through regulation of
      ER and Bcl-2.

PMID- 21174061
TI  - CD133 is a temporary marker of cancer stem cells in small cell lung cancer, but
      not in non-small cell lung cancer.
AB  - Lung cancer is the most common cause of cancer-related death worldwide. Current
      investigations in the field of cancer research have intensively focused on the
      'cancer stem cell' or 'tumor-initiating cell'. While CD133 was initially
      considered as a stem cell marker only in the hematopoietic system and the nervous
      system, the membrane antigen also identifies tumorigenic cells in certain solid
      tumors. In this study, we investigated the human lung cancer cell lines A549,
      H157, H226, Calu-1, H292 and H446. The results of real-time PCR analysis after
      chemotherapy drug selection and the fluorescence-activated cell sorting analysis
      showed that CD133 only functioned as a marker in the small cell lung cancer line
      H446. The sorted CD133+ subset presented stem cell-like features, including self
      renewal, differentiation, proliferation and tumorigenic capacity in subsequent
      assays. Furthermore, a proportion of the CD133+ cells had a tendency to remain
      stable, which may explain the controversies arising from previous studies.
      Therefore, the CD133+ subset should provide an enriched source of tumor
      initiating cells among H446 cells. Moreover, the antigen could be used as an
      investigative marker of the tumorigenic process and an effective treatment for
      small cell lung cancer.

PMID- 21174062
TI  - Down-regulation of osteopontin inhibits metastasis of hepatocellular carcinoma
      cells via a mechanism involving MMP-2 and uPA.
AB  - Osteopontin (OPN) has an important role in hepatocellular carcinoma (HCC)
      progression and metastasis. This study was to investigate the therapeutic
      potential of inhibition of OPN expression. A 2'-O-methoxyethylribose-modified
      phosphorothioate antisense oligonucleotides (ASO) was used to knock-down OPN
      expression in the human metastatic HCC cell line HCCLM6 and in nude mice
      orthotopically implanted with HCCLM6 showing highly spontaneous lung metastasis.
      Furthermore, we assessed the metastatic potential of HCCLM6 cells in vitro and in
      vivo after ASO treatment. Treatment of HCCLM6 cells with OPN ASO inhibited OPN
      mRNA expression in a dose- and time-dependent manner, whereas the control
      oligonucleotides had no effect. OPN ASO significantly suppressed migration and
      invasion of HCCLM6 cells in vitro. Specific suppression of OPN also inhibited
      matrix metalloproteinase 2 (MMP-2) and urokinase-type plasminogen activator (uPA)
      expression in HCCLM6 cells. In mice bearing orthotopical xenografts with HCCLM6,
      OPN inhibition following therapeutic treatment with OPN ASO significantly
      decreased lung metastases although tumor weight did not appear to be reduced.
      These findings suggest that OPN-targeted therapy may be a promising strategy for
      the treatment of HCC metastases.

PMID- 21174063
TI  - Leukocyte adhesion-GPCR EMR2 is aberrantly expressed in human breast carcinomas
      and is associated with patient survival.
AB  - EGF-like module containing mucin-like hormone receptor 2 (EMR2) is a leukocyte
      restricted adhesion G protein-coupled receptor. Aberrant expression of EMR2 and
      its highly homologous molecule CD97 have been reported in various human cancers.
      Herein, we investigate the expression of EMR2 in neoplastic breast human tissue
      and its relationship with patient survival. EMR2 expression in normal and
      neoplastic breast tissue was assessed by immunohistochemistry in sections from 10
      normal controls and micro-arrayed tissue cores from 69 cases of ductal carcinoma
      in situ (DCIS) and 272 invasive carcinomas. The pattern and intensity of staining
      was correlated with the clinicopathological characteristics of each case and the
      disease outcome. While absent in normal breast epithelium, EMR2 was significantly
      up-regulated in the cytoplasmic and nuclear compartments of both DCIS and
      invasive carcinoma, with invasive samples displaying significantly higher
      expression levels compared with in situ disease. In invasive disease, EMR2
      cytoplasmic expression was significantly associated with higher tumour grade but
      not with patient age, nodal status, tumour size, estrogen receptor expression,
      relapse-free or overall survival. In contrast, EMR2 nuclear expression correlated
      negatively with higher tumour grade. Of note, EMR2 nuclear expression was
      associated with longer relapse-free survival as well as overall survival. This
      study indicates that EMR2 is expressed in neoplastic breast epithelium and
      suggests that expression patterns of EMR2 are relevant in breast cancer
      progression. The association of improved patient survival with higher nuclear
      expression levels identifies EMR2 as a potential biomarker in patients with
      invasive breast cancer.

PMID- 21174064
TI  - Effect of classification based on combination of mutation and methylation in
      colorectal cancer prognosis.
AB  - Colorectal cancer (CRC) is caused by an accumulation of genetic alterations and
      epigenetic alterations. The molecular classification of CRCs based on genetic
      alterations and epigenetic alterations is evolving. Here, we examined mutations
      and methylation status in CRCs to determine if the combination of genetic and
      epigenetic alterations predicts prognosis. We examined 134 sporadic CRCs. We used
      the direct sequencing method to identify mutations in BRAF and AKT1, which are
      downstream of KRAS and PIK3CA, respectively, in the EGFR pathway. We used the
      Methylight method to determine the methylation status of hMLH1, p16, MINT1, MINT2
      and MINT31. Both BRAF and AKT1 mutations were found in only one case (0.75%).
      Aberrant methylation of hMLH1, p16, MINT1, MINT2 and MINT31 was detected in 22.4,
      35.1, 32.8, 59.7 and 41.0% of cases, respectively. The clinicopathological
      factors were not significantly correlated to mutation or methylation. Among the
      patients who had no mutation in the EGFR pathway, the overall survival was
      significantly shorter in the patients with methylation compared to the patients
      with no methylation in hMLH1 and p16 (p=0.0318). Methylation could play a key
      role in the prognosis of patients without mutations in the EGFR pathway. The
      combination of genetic and epigenetic alterations may be a good marker for the
      prognosis of CRC patients.

PMID- 21174065
TI  - Inhibin-alpha subunit expression in uterine endometrioid adenocarcinomas and
      endometrial cancer cell lines: a potential prognostic factor.
AB  - Inhibins/activins are secreted polypeptides of the transforming growth factor
      beta superfamily, forming a family of dimeric, disulphide-linked proteins.
      Inhibins are composed of an alpha-subunit and one of two possible beta-subunits.
      Both inhibins and activins have substantial roles in human reproduction and in
      endocrine-responsive tumors. However, the prognostic significance and clinical
      implications of the inhibin-alpha subunits in uterine endometrioid
      adenocarcinomas is still not clearly defined. A series of 231 uterine
      endometrioid adenocarcinomas of a previous well-characterized cohort were re
      evaluated for the expression of the inhibin-alpha subunit and correlated with
      several clinicopathological characteristics and clinical outcome. Additionally,
      several endometrial epithelial cell lines (Ishikawa plus and minus, HEC-1A, HEC
      1B and RL95-2) were analyzed for the expression of this subunit using
      immunohistochemical and molecular biological techniques. A significant
      association between the inhibin-alpha subunit and histological grade, surgical
      staging and myometrial invasion was demonstrated. Survival analysis demonstrated
      that inhibin-alpha immunoreactivity significantly affected progression-free,
      cause-specific and overall survival of patients with endometrioid
      adenocarcinomas. The analyzed endometrial cancer cell lines can also synthesize
      this subunit. Inhibin-alpha seems to have a substantial role in the
      carcinogenesis and pathology of uterine endometrioid carcinomas, and might be
      used as a marker to identify high-risk patients and may aid in the selection of
      patients for a more aggressive adjuvant therapy. Since uterine cancer cell lines
      express the inhibin-alpha subunit, they constitute adequate in vitro models for
      assessing its function in endometrial carcinogenesis. However, further research
      is warranted to elucidate the possible implications of inhibin-alpha in
      endometrial carcinogenesis.

PMID- 21174066
TI  - MALDI imaging as a specific diagnostic tool for routine cervical cytology
      specimens.
AB  - Cervical squamous cell carcinoma (SCC) is among the most common malignancies in
      women worldwide. In developed countries routine cytology screening has
      dramatically reduced SCC mortality within the last three decades. High risk (HR)
      human papilloma virus (HPV) infection is the main causal factor in nearly 100% of
      invasive SCCs, in most cases of low grade squamous intraepithelial lesion (LSIL)
      and in nearly all cases of high grade squamous intraepithelial lesion (HSIL).
      Detection of HR-HPV DNA has been extensively evaluated for the triage of patients
      with low grade cytological abnormalities in order to identify those at greatest
      risk for underlying or developing HSIL or SCC. However, the vast majority of HR
      HPV-positive precursor lesions will not progress to invasive cancer. A variety of
      other screening tools are available which aim to stratify clinically significant
      HPV infections and cytological alterations. Matrix assisted laser
      desorption/ionization (MALDI) imaging mass spectrometry is a promising technology
      to assist in this endeavor. It delivers accurate mass spectrometric information
      of the sample's proteins and enables the visualization of the spatial
      distribution of protein expression profiles in correlation with histological
      features. In this study, 18 samples with Pap IIID or higher (>LSIL) and 14
      samples with Pap I-II (WNL) were analyzed by MALDI imaging mass spectrometry
      (IMS). A genetic algorithm was applied to classify spectra resulting in an
      overall cross validation, sensitivity for Pap IIID and Pap I-II of 83.7%, 88.9%
      and 78.6%, respectively. As this IMS based approach allows for unbiased and
      automated classifiction of cytological samples it appears to be a promising tool
      for stratification of cervical Pap smears.

PMID- 21174067
TI  - Combined treatment with bortezomib plus bafilomycin A1 enhances the cytocidal
      effect and induces endoplasmic reticulum stress in U266 myeloma cells: crosstalk
      among proteasome, autophagy-lysosome and ER stress.
AB  - Bortezomib (BZ), a first line 26S proteasome inhibitor, induces a potent
      cytocidal effect with caspase-3 activation in multiple myeloma (MM) cell lines.
      Since IkappaBalpha is a substrate of the proteasome, the initial rationale for
      using BZ in MM has been to inhibit NF-kappaB. However, BZ rather activated NF
      kappaB activity in U266 cells. BZ induces autophagy as well as endoplasmic
      reticulum (ER) stress in various cell lines tested. Inhibition of initial
      autophagosome formation by treatment with either 3-methyladenine or siRNA for
      LC3B in U266 cells and knockdown of the atg5 gene in a murine embryonic
      fibroblastic cell line all resulted in attenuation of BZ-induced cell death. In
      contrast, combined treatment with BZ and bafilomycin A1 (BAF), which is a
      specific inhibitor of vacuolar-ATPase and is used as an autophagy inhibitor at
      the late stage, resulted in synergistic cytotoxicity, compared with that by
      either BZ or BAF alone. BAF treatment also induced ER stress, but the kinetics of
      inductions of ER stress-related genes [e.g. CHOP (GADD153) and GRP78] completely
      differed between BZ- and BAF-treatments: BZ induced these ER stress markers
      within 8 h, whereas treatment with BAF required more than 48 h in U266 cells. In
      order to synchronize ER stress, we pre-treated U266 cells with BAF for 48 h,
      followed with BZ for 48 h. The sequential treatment with BAF and BZ induced a
      further enhanced cytotoxicity, compared with the simultaneous combination of BAF
      and BZ. These data suggest crosstalk among the ubiquitin-proteasome system, the
      autophagy-lysosome system, and ER stress. Controlling these interactions and
      kinetics appears to have important implications for optimizing clinical cancer
      treatment including MM-therapy.

PMID- 21174068
TI  - [Anastomoses in the upper gastrointestinal tract].
AB  - BACKGROUND: Anastomotic leaks are the major postoperative complications mainly
      due to technical difficulties. The aim was to review anastomotic techniques and
      risk factors for leak development. METHODS: A Pubmed search was performed using
      the terms esophagogastric/esophagojejunal anastomosis, gastrojejunostomy, gastric
      bypass, esophagectomy, anastomotic leak/risk factors, gastrectomy, TEA, fluid
      management, early enteral feeding and reinforcement. English and German
      literature sources were included with the accent on recent prospective randomized
      controlled trials (pRCT) with high numbers of cases as well as meta-analyses.
      CONCLUSIONS: There is not enough evidence to recommend either hand sewn or
      mechanical anastomoses. Surgical skills and routine as well as precise work are
      necessary to reduce complications. Although stapling leads to uniformity of
      anastomoses it cannot compensate for surgical deficits.

PMID- 21174069
TI  - [PSP Scale: German version of the Personal and Social Performance Scale: valid
      instrument for the assessment of psychosocial functioning in the treatment of
      schizophrenia].
AB  - In the treatment of schizophrenia, the domain of psychosocial functioning is an
      important aspect of therapeutic success that should be considered in addition to
      the reduction of psychopathology. Valid and standardised measures are necessary
      for diagnostics and the assessment of patients" personal, social and professional
      functioning. The German version of the Personal and Social Performance (PSP)
      Scale (with its four subdimensions: "socially useful activities, work and study
      included", "personal and social relationships", "self-care" and "disturbing and
      aggressive behaviour") was administered to patients with schizophrenia in
      previous studies. These data demonstrated this scale to be a reliable, valid and
      efficient tool for measuring psychosocial functioning in schizophrenia. Thus, it
      is argued that, for everyday clinical practice, the PSP Scale is useful for the
      assessment of psychosocial functioning in schizophrenia during short, medium and
      long-term treatment courses.

PMID- 21174071
TI  - [Restless legs syndrome and cardiovascular risk].
AB  - Large epidemiological studies have repeatedly suggested a possible association
      between restless legs syndrome (RLS) and common cardiovascular diseases and
      cardiovascular risk factors. Patients complaining of symptoms of RLS were also
      more likely to suffer from coronary artery disease, stroke, or, in some
      instances, hypertension. The underlying pathogenesis of the disease association
      depicted above has not been elucidated conclusively. Increased activation of the
      sympathetic nervous system - due to the RLS itself and the frequently
      accompanying periodic limb movements - has been linked to increased
      cardiovascular stress in patients with RLS.

PMID- 21174072
TI  - [The supremacy of vision in medical diagnostics : Prof. Stefan Feuerbach's 65th
      birthday].

PMID- 21174070
TI  - [Diagnosis and treatment of neuromyelitis optica. Consensus recommendations of
      the Neuromyelitis Optica Study Group].

PMID- 21174073
TI  - [Isolated direct MR arthrography in ABER position or conventional MR arthrography
      for identification of partial ruptures of the supraspinatus tendon].

PMID- 21174074
TI  - Human beta cell proliferation by glucose--a complex scenario.

PMID- 21174075
TI  - Effects of a lifestyle intervention in metabolically benign and malign obesity.
AB  - AIMS/HYPOTHESIS: We and others recently characterised metabolically benign or
      healthy obesity (MHO). In the present study we investigated whether a lifestyle
      intervention is sufficient to place obese insulin-resistant (OIR) individuals in
      a position where the possible metabolic consequences are similar to those for MHO
      individuals. METHODS: A total of 262 non-diabetic individuals participated in a 9
      month lifestyle intervention programme. Obese individuals (BMI >= 30.0 kg/m(2))
      were stratified, based on their insulin sensitivity (IS) estimated from an OGTT,
      into MHO (IS in the upper quartile, n = 26) and OIR (IS in the lower three
      quartiles, n = 77). Total body and visceral fat were measured by magnetic
      resonance (MR) tomography and liver fat by (1)H-MR spectroscopy. RESULTS: During
      the intervention, visceral fat decreased significantly in both groups (both p <=
      0.009), whereas total body and liver fat decreased only in the OIR group (p <
      0.0001; MHO p = 0.12 for total body fat and p = 0.47 for liver fat). IS improved
      in the OIR group (p < 0.0001), but remained essentially unchanged in the MHO
      group (p = 0.30). However, despite the significant increase in the OIR group, IS
      at follow-up barely exceeded 50% of the IS of the MHO group (OIR 9.30 +/- 0.53
      arbitrary units [AU]; MHO 16.41 +/- 1.05 AU; p < 0.0001).
      CONCLUSIONS/INTERPRETATION: IS improves during the lifestyle intervention in OIR
      individuals. However, it does not reach a level where adequate protection from
      type 2 diabetes and cardiovascular disease is expected. Thus, stratification of
      obese individuals based on their metabolic phenotype is important to identify
      those who are likely to need early pharmacological treatment in addition to the
      lifestyle intervention.

PMID- 21174076
TI  - [Arthroscopic reconstruction of the glenoid concavity with an autologous bone
      block procedure].
AB  - Open bone block procedures for glenohumeral stabilization have been used for a
      long time in different variations. Recently published clinical and radiological
      studies were able to demonstrate that anatomical reconstruction of the glenoid
      concavity using a pre-shaped iliac crest autograft represents an effective and
      durable treatment option for bony-mediated anterior shoulder instability. With
      the advancement of arthroscopic techniques and the development of sophisticated
      instruments and implants apposition of the bone block can now be performed via an
      all-arthroscopic approach. This article describes the history, principles,
      indications, surgical technique and early results of the all-arthroscopic iliac
      crest bone block procedure.

PMID- 21174077
TI  - [Arthroscopic rotator cuff construction : Current state of refixation
      techniques].
AB  - The treatment of rotator cuff tears is affected by numerous factors. In addition
      to the patient's age, quality of blood supply, age and size of the tear and fatty
      infiltration, the refixation technique is important to ensure successful
      treatment. In recent years a trend towards arthroscopic operation techniques has
      been observed due to new developments in the field.The most important principles
      of arthroscopic refixation techniques currently used are presented. Special
      attention is paid to the type of suture, suture anchors and anchor arrangements
      used. Biomechanics and footprint coverage of double row constructions are
      superior to single row but clinical results do not show any clear advantages. If
      feasible, double row rotator cuff repair with lateral suture bridging seems to
      represent presently a useful technique with a superior rate of tendon healing.

PMID- 21174078
TI  - Measurement of transurethral bladder neck displacement during tension-free
      vaginal tape procedure.
AB  - INTRODUCTION AND HYPOTHESIS: The rigid catheter guide is used during the tension
      free vaginal tape (TVT) procedure to direct the bladder neck away from the
      retropubic passage of the sling arm. Our aim was to measure, using transperineal
      ultrasound, the amount of bladder neck displacement by the rigid catheter guide
      during TVT placement. METHODS: This is a prospective cohort of 28 patients
      undergoing the TVT procedure, with or without concomitant pelvic organ prolapse
      repair. Spearman's correlation was used to analyze the bladder neck displacement
      from the midline. RESULTS: The median right-sided bladder neck displacement
      distance was 1.4 cm (0.6-2.0), and the median left-sided bladder neck
      displacement distance was 1.4 cm (0.8-2.0). The overall perforation rate was 14%
      (4/28). CONCLUSIONS: Bladder neck displacement with the Mandarin guide results in
      ~1.4 cm of lateral movement.

PMID- 21174079
TI  - Celecoxib induces heme oxygenase-1 expression in macrophages and vascular smooth
      muscle cells via ROS-dependent signaling pathway.
AB  - The multiple cytoprotective mechanisms of heme oxygenase (HO)-1 make it a
      promising therapeutic target. This study investigated whether the selective
      cyclooxygenase (COX)-2 inhibitor, celecoxib, can upregulate HO-1 expression.
      Murine J774 macrophages and rat aortic vascular smooth muscle cells (VSMCs) were
      used to study the effect of celecoxib on HO-1 expression. A signal transduction
      pathway involving reactive oxygen species (ROS) was also investigated. We found
      that celecoxib can upregulate HO-1 gene and protein expressions in J774
      macrophages and VSMCs. This effect was not diminished by prostaglandin E(2) or
      15dPGJ(2), while it was additive to hypoxia-induced HO-1 expression, suggesting
      an event independent of COX-2 activity or hypoxia-inducible factor-1alpha.
      Moreover, celecoxib activated ERK, p38, Akt, and Nrf2 as well as increased ROS
      production. All these events contributed to the increase in the expression of HO
      1 caused by celecoxib. In this study, we also, for the first time, demonstrated
      that AMP-activated protein kinase (AMPK) can mediate HO-1 expression via the
      downstream activation of p38 and Akt. However, the HO-1-inducing actions of
      celecoxib and hypoxia were not associated with AMPK. This study demonstrates a
      COX-2-independent action of celecoxib in upregulating HO-1 in macrophages and
      VSMCs. This action is dependent on ROS, Akt, ERK, p38, and Nrf2 activation. These
      findings provide new insights into the action mechanism of celecoxib with broad
      implications for anti-inflammation therapy.

PMID- 21174080
TI  - Effects of serotonin (5-HT)1A and 5-HT2A receptor agonists on schedule-controlled
      responding in rats: drug combination studies.
AB  - RATIONALE: Indirect-acting serotonin (5-HT) receptor agonists (e.g., selective 5
      HT reuptake inhibitors [SSRI]) stimulate multiple 5-HT receptors, although the
      role of particular receptors as well as interaction(s) among different receptors
      in the therapeutic effects of SSRIs is not fully understood. OBJECTIVES:
      Relatively few studies have systematically examined direct-acting agonists in
      combination. This study examined the 5-HT(1A) receptor agonists 8-hydroxy-2-(di-n
      propylamino) tetralin hydrochloride (8-OH-DPAT; 0.01-10.0 mg/kg) and 3-chloro-4
      fluorophenyl-4-fluoro-4-([(5-methyl-6-methylamino-pyridin-2-ylmethyl)-amino]
      methyl)-piperidin-1-yl-methanone (F13714; 0.01-1.0 mg/kg) and the 5-HT(2A)
      receptor agonists 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM; 0.32-10.0
      mg/kg) and dipropyltryptamine (DPT; 1.0-32.0 mg/kg), alone and in combination, in
      rats responding under a fixed ratio schedule of food presentation. RESULTS: When
      administered alone, each drug decreased the rate of responding in a dose-related
      manner with the potency order being F13714 > 8-OH-DPAT > DOM > DPT. WAY100635 (5
      HT(1A) receptor antagonist; 0.01-0.1 mg/kg) attenuated the rate-decreasing
      effects of 8-OH-DPAT and F13714 while MDL100907 (5-HT(2A) receptor antagonist;
      0.01-0.1 mg/kg) attenuated the rate-decreasing effects of DOM and DPT. Dose
      addition analysis showed that the interaction between 8-OH-DPAT and F13714, as
      well as the interaction between DOM and DPT, was additive. In contrast, the
      interaction between 8-OH-DPAT and DOM, as well as the interaction between F13714
      and DOM, was infra-additive. CONCLUSIONS: This study shows that for some dose
      combinations, agonist actions at one 5-HT receptor subtype attenuate agonist
      actions at another 5-HT receptor subtype; thus, the combined neuropharmacological
      actions and therapeutic effects of indirect-acting agonists are not likely to be
      adequately characterized by examining in isolation activity at particular 5-HT
      receptor subtypes.

PMID- 21174081
TI  - Anomalous origin of the occipital artery diagnosed by magnetic resonance
      angiography.
AB  - INTRODUCTION: It is well known that the occipital artery (OA) can arise from the
      internal carotid artery (ICA) or vertebral artery (VA). However, the incidence of
      an anomalously originating OA has not been reported. We investigate its incidence
      and characteristic features on magnetic resonance angiography (MRA). METHODS: We
      retrospectively reviewed MRA images of 2,866 patients that included the carotid
      bifurcation; images were obtained using a standard noncontrast MRA protocol and
      two 1.5-T MR units. RESULTS: We diagnosed six cases (seven arteries) of
      anomalously originating OA, which represented an incidence of 0.21%. The OA arose
      from the ICA in four patients (five arteries), from the carotid bifurcation in
      one, and from the VA in one. Five of the seven arteries occurred on the right.
      CONCLUSION: Anomalously originating OA is rare and occurs with right-side
      predominance. Correct diagnosis is necessary before or during cerebral
      angiography, especially when selective catheterization to the OA is required.

PMID- 21174082
TI  - Clinical and radiological distinction between spondylothoracic dysostosis (Lavy
      Moseley syndrome) and spondylocostal dysostosis (Jarcho-Levin syndrome).
AB  - In 1938, Saul Jarcho and Paul Levin from Johns Hopkins Hospital reported cases of
      thoracic insufficiency due to vertebral and rib anomalies. Nearly 30 years later,
      in 1966, Norman Lavy and associates from Indiana University reported a similar
      syndrome in a family from Puerto Rico. Lavy's description was followed by a
      report by John E. Moseley from New York City, where the name spondylothoracic
      dysplasia (dysostosis) was first used. For more than half a century, there has
      been confusion regarding the distinction between these two phenotypically similar
      syndromes that cause thoracic insufficiency. Spondylocostal dysostosis (SCD), or
      Jarcho-Levin syndrome, causes mild to moderate respiratory insufficiency, is
      panethnic and has been linked to genes such as DLL3, which is known to be
      associated with the Notch pathway. In contrast, spondylothoracic dysostosis
      (STD), or Lavy-Moseley syndrome, results in more severe respiratory compromise,
      is largely linked to Puerto Rican cohorts and is thought to be associated to the
      MESP2 gene, also a Notch pathway gene. Long-term studies of Puerto Rican cohorts
      with STD contradicts the previously held belief that individuals affected with
      STD have markedly diminished life expectancy with as many as 25% surviving into
      later childhood and adult life.

PMID- 21174083
TI  - Radiology residents' experience with intussusception reduction.
AB  - BACKGROUND: Residents should be exposed to adequate procedural volume to act
      independently upon completion of training. Informal inquiry led us to question
      whether residents encounter enough intussusception reductions to become
      comfortable with the procedure. OBJECTIVE: We sought to determine radiology
      residents' exposure to intussusception reductions, and whether their experiences
      vary by region or institution. MATERIALS AND METHODS: U.S. radiology residency
      program directors were asked to encourage their residents to complete a 12
      question online survey describing characteristics of their pediatric radiology
      department, experiences with intussusception reduction, and confidence in their
      own ability to perform the procedure. RESULTS: Six hundred sixty-four residents
      responded during the study period. Of those, 308 (46.4%) had not experienced an
      intussusception reduction, and 228 (34%) had experienced only one or two. Twenty
      two percent of fourth-year residents had never experienced an intussusception
      reduction, and 21% had experienced only one. Among second- through fourth-year
      residents, only 99 (18.3%) felt confident that they could competently reduce an
      intussusception (P < 0.0001), and 336 (62.2%) thought they would benefit from a
      computer-assisted training model simulating intussusception reduction (P <
      0.0001). CONCLUSION: Radiology residents have limited opportunity to learn
      intussusception reduction and therefore lack confidence. Most think they would
      benefit from additional training with a computer-simulation model.

PMID- 21174084
TI  - MRI findings in multifetal pregnancies complicated by twin reversed arterial
      perfusion sequence (TRAP).
AB  - BACKGROUND: Twin reversed arterial perfusion sequence (TRAP) is a rare
      complication in multifetal monochorionic pregnancies in which a normal "pump"
      twin provides circulation to an abnormal acardiac co-twin, resulting in high
      output cardiac dysfunction in the pump twin. OBJECTIVE: To define fetal MRI
      findings of TRAP sequence. MATERIALS AND METHODS: Fetal MR images were
      retrospectively reviewed in 35 pregnancies complicated by TRAP sequence.
      Abnormalities of the pump twin, acardiac twin, umbilical cord, placenta and
      amniotic fluid were reviewed. RESULTS: Acardiac twins were classified as:
      acephalus (51%), anceps (40%), amorphus (9%), acormus (0%). Common findings in
      acardiac twins include subcutaneous edema (77%), absent cardiac structures (86%),
      absent or abnormal thoracic cavity (100%), abnormal abdominal organs (100%),
      superior limbs absent (46%) or abnormal (51%), and inferior limbs present but
      abnormal (83%). There were pump twin findings of cardiac dysfunction in 43% and
      intracranial ischemic changes in 3%. Umbilical cord anomalies were present in
      97%. CONCLUSION: Acardiac twins present with a predictable pattern of
      malformation with poorly developed superior structures, more normally formed
      inferior structures and absent or rudimentary heart. Although usually absent,
      abnormal heart structures can be seen and do not exclude TRAP sequence. Pump
      twins are commonly normal with exception of findings of cardiac dysfunction and
      possible brain ischemia.

PMID- 21174085
TI  - Ectopia cordis with tetralogy of Fallot in an infant with pentalogy of Cantrell:
      high-pitch MDCT exam.
AB  - We report the MDCT findings of a 17-month-old girl with Cantrell's pentalogy, a
      rare congenital disease characterized by several defects in the ventral
      thoracoabdominal wall including ectopia cordis, and, in this patient, associated
      with tetralogy of Fallot. This case provides an example of the utility of a wide
      volume in coverage and high-pitch MDCT scan in the evaluation of complex
      cardiovascular anatomy in infants with congenital heart disease without the need
      of an ECG-gating acquisition.

PMID- 21174086
TI  - Aquatic microbial habitats within a neotropical rainforest: bromeliads and pH
      associated trends in bacterial diversity and composition.
AB  - Tank-forming bromeliads, suspended in the rainforest canopy, possess foliage
      arranged in compact rosettes capable of long-term retention of rainwater. This
      large and unique aquatic habitat is inhabited by microorganisms involved in the
      important decomposition of impounded material. Moreover, these communities are
      likely influenced by environmental factors such as pH, oxygen, and light.
      Bacterial community composition and diversity was determined for the tanks of
      several bromeliad species (Aechmea and Werauhia) from northern Costa Rica, which
      span a range of parameters, including tank morphology and pH. These were compared
      with a nearby forest soil sample, an artificial tank (amber bottle), and a
      commercially available species (Aechmea). Bacterial community diversity, as
      measured by 16S rRNA analysis and tRFLP, showed a significant positive
      correlation with tank pH. A majority of 16S rRNA bacterial phylotypes found in
      association with acidic bromeliad tanks of pH < 5.1 were affiliated with the
      Alphaproteobacteria, Acidobacteria, Planctomycetes, and Bacteroidetes, and were
      similar to those found in acidic peat bogs, yet distinct from the underlying soil
      community. In contrast, bromeliads with tank pH > 5.3, including the commercial
      bromeliad with the highest pH (6.7), were dominated by Betaproteobacteria,
      Firmicutes, and Bacteroidetes. To empirically determine the effect of pH on
      bacterial community, the tank pH of a specimen of Aechmea was depressed, in the
      field, from 6.5 to 4.5, for 62 days. The resulting community changed predictably
      with decreased abundance of Betaproteobacteria and Firmicutes and a concomitant
      increase in Alphaproteobacteria and Acidobacteria. Collectively, these results
      suggest that bromeliad tanks provide important habitats for a diverse microbial
      community, distinct from the surrounding environment, which are influenced
      greatly by acid-base conditions. Additionally, total organic carbon (~46%) and
      nitrogen (~2%) of bromeliad-impounded sediment was elevated relative to soil and
      gene surveys confirmed the presence of both chitinases and nitrogenases,
      suggesting that bromeliad tanks may provide important habitats for microbes
      involved in the biological cycling of carbon and nitrogen in tropical forests.

PMID- 21174087
TI  - Cerenkov radioactive optical imaging: a promising new strategy.

PMID- 21174088
TI  - Bio-effect model applied to 131I radioimmunotherapy of refractory non-Hodgkin's
      lymphoma.
AB  - PURPOSE: Improved data collection methods have improved absorbed dose estimation
      by tracking activity distributions and tumor extent at multiple time points,
      allowing individualized absorbed dose estimation. Treatment with tositumomab and
      (131)I-tositumomab anti-CD20 radioimmunotherapy (BEXXAR) yields a cold antibody
      antitumor response (cold protein effect) and a radiation response. Biologically
      effective contributions, including the cold protein effect, are included in an
      equivalent biological effect model that was fit to patient data. METHODS: Fifty
      seven tumors in 19 patients were followed using 6 single proton emission computed
      tomography (SPECT)/CT studies, 3 each post tracer (5 mCi) and therapy (~100 mCi)
      injections with tositumomab and (131)I-tositumomab. Both injections used
      identical antibody mass, a flood dose of 450 mg plus 35 mg of (131)I tagged
      antibody. The SPECT/CT data were used to calculate absorbed dose rate
      distributions and tumor and whole-body time-activity curves, yielding a space
      time dependent absorbed dose rate description for each tumor. Tumor volume
      outlines on CT were used to derive the time dependence of tumor size for tracer
      and therapy time points. A combination of an equivalent biological effect model
      and an inactivated cell clearance model was used to fit absorbed dose sensitivity
      and cold effect sensitivity parameters to tumor shrinkage data, from which
      equivalent therapy values were calculated. RESULTS: Patient responses were
      categorized into three groups: standard radiation sensitivity with no cold effect
      (7 patients), standard radiation sensitivity with cold effect (11 patients), and
      high radiation sensitivity with cold effect (1 patient). CONCLUSION: Fit
      parameters can be used to categorize patient response, implying a potential
      predictive capability.

PMID- 21174089
TI  - Molecular imaging of atherosclerosis in translational medicine.
AB  - Functional characterization of atherosclerosis is a promising application of
      molecular imaging. Radionuclide-based techniques for molecular imaging in the
      large arteries (e.g. aorta and carotids), along with ultrasound and magnetic
      resonance imaging (MRI), have been studied both experimentally and in clinical
      studies. Technical factors including cardiac and respiratory motion, low spatial
      resolution and partial volume effects mean that noninvasive molecular imaging of
      atherosclerosis in the coronary arteries is not ready for prime time. Positron
      emission tomography imaging with fluorodeoxyglucose can measure vascular
      inflammation in the large arteries with high reproducibility, and signal change
      in response to anti-inflammatory therapy has been described. MRI has proven of
      value for quantifying carotid artery inflammation when iron oxide nanoparticles
      are used as a contrast agent. Macrophage accumulation of the iron particles
      allows regression of inflammation to be measured with drug therapy. Similarly,
      contrast-enhanced ultrasound imaging is also being evaluated for functional
      characterization of atherosclerotic plaques. For all of these techniques,
      however, large-scale clinical trials are mandatory to define the prognostic
      importance of the imaging signals in terms of risk of future vascular events.

PMID- 21174090
TI  - Radiosynthesis and in vivo evaluation of a series of substituted 11C
      phenethylamines as 5-HT (2A) agonist PET tracers.
AB  - PURPOSE: Positron emission tomography (PET) imaging of serotonin 2A (5-HT(2A))
      receptors with agonist tracers holds promise for the selective labelling of 5
      HT(2A) receptors in their high-affinity state. We have previously validated
      [(11)C]Cimbi-5 and found that it is a 5-HT(2A) receptor agonist PET tracer. In an
      attempt to further optimize the target-to-background binding ratio, we modified
      the chemical structure of the phenethylamine backbone and carbon-11 labelling
      site of [(11)C]Cimbi-5 in different ways. Here, we present the in vivo validation
      of nine novel 5-HT(2A) receptor agonist PET tracers in the pig brain. METHODS:
      Each radiotracer was injected intravenously into anaesthetized Danish Landrace
      pigs, and the pigs were subsequently scanned for 90 min in a high-resolution
      research tomography scanner. To evaluate 5-HT(2A) receptor binding, cortical
      nondisplaceable binding potentials (BP(ND)) were calculated using the simplified
      reference tissue model with the cerebellum as a reference region. RESULTS: After
      intravenous injection, all compounds entered the brain and distributed
      preferentially into the cortical areas, in accordance with the known 5-HT(2A)
      receptor distribution. The largest target-to-background binding ratio was found
      for [(11)C]Cimbi-36 which also had a high brain uptake compared to its analogues.
      The cortical binding of [(11)C]Cimbi-36 was decreased by pretreatment with
      ketanserin, supporting 5-HT(2A) receptor selectivity in vivo. [(11)C]Cimbi-82 and
      [(11)C]Cimbi-21 showed lower cortical BP(ND), while [(11)C]Cimbi-27, [(11)C]Cimbi
      29, [(11)C]Cimbi-31 and [(11)C]Cimbi-88 gave rise to cortical BP(ND) similar to
      that of [(11)C]Cimbi-5. CONCLUSION: [(11)C]Cimbi-36 is currently the most
      promising candidate for investigation of 5-HT(2A) receptor agonist binding in the
      living human brain with PET.

PMID- 21174091
TI  - The use of a portable gamma camera for preoperative lymphatic mapping: a
      comparison with a conventional gamma camera.
AB  - PURPOSE: Planar lymphoscintigraphy is routinely used for preoperative sentinel
      node visualization, but large gamma cameras are not always available. We
      evaluated the reproducibility of lymphatic mapping with a smaller and portable
      gamma camera. METHODS: In two centres, 52 patients with breast cancer received
      preoperative lymphoscintigraphy with a conventional gamma camera with a field of
      view of 40 * 40 cm. Static anterior and lateral images were performed at 15 min,
      2 h and 4 h after injection of the radiotracer ((99m)Tc-nanocolloid). At 2 h
      after injection, anterior and oblique images were also performed with a portable
      gamma camera (Sentinella, Oncovision) positioned to obtain a field of view of 20
      * 20 cm. Visualization of lymphatic drainage on conventional images and images
      with the portable device were compared for number of nodes depicted, their
      intensity and localization of sentinel nodes. RESULTS: The images performed with
      the conventional gamma camera depicted sentinel nodes in 94%, while the portable
      gamma camera showed drainage in 73%. There was however no significant difference
      in visualization between the two devices when a lead shield was used to mask the
      injection area in 43 patients (95 vs 88%, p = 0.25). Second-echelon nodes were
      visualized in 62% of the patients with the conventional gamma camera and in 29%
      of the cases with the portable gamma camera. CONCLUSION: Preoperative imaging
      with a portable gamma camera fitted with a pinhole collimator to obtain a field
      of view of 20 * 20 cm is able to depict sentinel nodes in 88% of the cases, if a
      lead shield is used to mask the injection site. This device may be useful in
      centres without the possibility to perform a preoperative image.

PMID- 21174092
TI  - A novel computer-assisted image analysis of [123I]beta-CIT SPECT images improves
      the diagnostic accuracy of parkinsonian disorders.
AB  - PURPOSE: The purpose of this study was to develop an observer-independent
      algorithm for the correct classification of dopamine transporter SPECT images as
      Parkinson's disease (PD), multiple system atrophy parkinson variant (MSA-P),
      progressive supranuclear palsy (PSP) or normal. METHODS: A total of 60 subjects
      with clinically probable PD (n = 15), MSA-P (n = 15) and PSP (n = 15), and 15 age
      matched healthy volunteers, were studied with the dopamine transporter ligand
      [(123)I]beta-CIT. Parametric images of the specific-to-nondisplaceable
      equilibrium partition coefficient (BP(ND)) were generated. Following a voxel-wise
      ANOVA, cut-off values were calculated from the voxel values of the resulting six
      post-hoc t-test maps. The percentages of the volume of an individual BP(ND) image
      remaining below and above the cut-off values were determined. The higher
      percentage of image volume from all six cut-off matrices was used to classify an
      individual's image. For validation, the algorithm was compared to a conventional
      region of interest analysis. RESULTS: The predictive diagnostic accuracy of the
      algorithm in the correct assignment of a [(123)I]beta-CIT SPECT image was 83.3%
      and increased to 93.3% on merging the MSA-P and PSP groups. In contrast the
      multinomial logistic regression of mean region of interest values of the caudate,
      putamen and midbrain revealed a diagnostic accuracy of 71.7%. CONCLUSION: In
      contrast to a rater-driven approach, this novel method was superior in
      classifying [(123)I]beta-CIT-SPECT images as one of four diagnostic entities. In
      combination with the investigator-driven visual assessment of SPECT images, this
      clinical decision support tool would help to improve the diagnostic yield of
      [(123)I]beta-CIT SPECT in patients presenting with parkinsonism at their initial
      visit.

PMID- 21174093
TI  - Survival after intratumoral interleukin-2 treatment of 72 melanoma patients and
      response upon the first chemotherapy during follow-up.
AB  - Systemic high-dose interleukin-2 (IL-2) treatment achieves long-term survival in
      a subset of advanced patients with melanoma. As we reported previously,
      intratumoral IL-2 induced complete local responses in more than 60% of melanoma
      patients. This study aimed to analyze the long-term outcome of 72 patients
      treated in two prior trials. Melanoma patients (49 stage III, 23 stage IV) with
      injectable metastases received intratumoral IL-2 injections thrice weekly at
      individually escalated doses (median duration, 6.5 weeks; median total IL-2 dose,
      72 MIU; median number of injected metastases, 10). The observed 2-year overall
      survival rates were 95.5% for stage III patients with cutaneous metastases only
      (stage IIIB), 72% for those with combined cutaneous and lymph node involvement
      (stage IIIC), 66.7% for stage IV patients with disease limited to distant soft
      tissue metastases (stage IV M1a), and 9.1% for those with visceral metastases
      (stage IV M1b and stage IV M1c). Thirty patients who reported recurrence of
      unresectable distant metastases subsequently received chemotherapy in the further
      course of disease and showed an overall response rate of 36.7% (16.7% complete
      responses, 20% partial responses). A high total dose of IL-2 and a
      dacarbazine/temozolomide-based chemotherapy regimen were variables correlated
      with a clinical response. In conclusion, patients with cutaneous metastasis
      without lymph node involvement in stage III and with soft-tissue metastasis
      without visceral involvement in stage IV showed unexpected favorable survival
      rates after intratumoral treatment with IL-2. Furthermore, the intratumoral IL-2
      treatment seemed to be associated with increased complete and partial responses
      in subsequent chemotherapies.

PMID- 21174095
TI  - From multislice CT to whole-body biomarker imaging in lymphoma patients.
AB  - Until recently, only nuclear medicine techniques allowed combining whole-body
      anatomical and functional information. Now, diffusion-weighted imaging seeks to
      compete with these techniques in the field of oncology, providing assessment of
      tumour spread, characterizing lesions and evaluating therapeutic response. The
      first issue has been widely evaluated since the first published whole-body
      diffusion-weighted images looking like scintigraphy. Optimal background
      suppression and diffusion weighting highlighted tumours with restricted
      diffusion. For the two latter issues, ADC seems to represent the key element; it
      should allow differentiation between benign and malignant tissue, and active from
      inactive lesions after treatment. This is of paramount importance for the
      monitoring of lymphomas treated with chemotherapy alone, or for solid tumors
      treated by neoadjuvant therapies. However, imaging protocols still differ between
      studies, and there is considerable overlap in ADC values between healthy and
      neoplastic tissues. Despite this difficulty to identify a clinically reliable
      threshold for malignancy, there is no doubt that ADC will represent as a reliable
      biomarker in the future for some malignancies, and lymphomas represent a helpful
      model for this purpose.

PMID- 21174094
TI  - Exosomes: immune properties and potential clinical implementations.
AB  - To communicate, cells are known to release in their environment proteins which
      bind to receptors on surrounding cells. But cells also secrete more complex
      structures, called membrane vesicles, composed of a lipid bilayer with inserted
      transmembrane proteins, enclosing an internal content of hydrophilic components.
      Exosomes represent a specific subclass of such secreted membrane vesicles, which,
      despite having been described more than 20 years ago by two groups studying
      reticulocyte maturation, have only recently received attention from the
      scientific community. This renewed interest originated first from the description
      of exosome secretion by antigen-presenting cells, suggesting a potential role in
      immune responses, and very recently by the identification of the presence of RNA
      (both messenger and microRNA) in exosomes, suggesting a potential transfer of
      genetic information between cells. In this review, we will describe the
      conclusions of 20 years of studies on the immune properties of exosomes and the
      most recent advances on their roles and potential uses as markers or as
      therapeutic tools during pathologies, especially in cancer.

PMID- 21174096
TI  - Molecular imaging in oncology: the acceptance of PET/CT and the emergence of
      MR/PET imaging.
AB  - In the last decade, PET-only systems have been phased out and replaced with PET
      CT systems. This merger of a functional and anatomical imaging modality turned
      out to be extremely useful in clinical practice. Currently, PET-CT is a major
      diagnostic tool in oncology. At the dawn of the merger of MRI and PET, another
      breakthrough in clinical imaging is expected. The combination of these imaging
      modalities is challenging, but has particular features such as imaging biological
      processes at the same time in specific body locations.

PMID- 21174097
TI  - Indeterminate adnexal masses at ultrasound: effect of MRI imaging findings on
      diagnostic thinking and therapeutic decisions.
AB  - OBJECTIVE: To determine the impact of MRI including DWI on therapeutic decision
      making and costs in the work-up of patients with a indeterminate adnexal mass on
      ultrasound. METHODS: Thirty-eight patients with indeterminate ovarian lesions
      scheduled for surgery were included in this prospective study. In a
      questionnaire, the surgeon characterised the lesions based on a morphological
      score and determined the surgical procedure. The assessment was re-evaluated
      knowing MR findings and correlated with the final diagnosis. A cost-benefit
      analysis of MRI was performed. The impact of including DWI in the MR protocol was
      assessed. RESULTS: MRI provided major diagnostic information in 11/38 cases
      (28.9%) resulting in abstention from surgery in 5 cases; moderate additional
      information was recorded in 10/38 (26.3%) patients. Overall a net cost saving
      (3'676 EUR) was achieved. DWI did not show a significant difference between
      benign and malignant lesions. Teratomas yielded significantly lower mean ADC
      values (0.597 * 10(-3) mm(2)/s) compared with all other adnexal lesions (1.812 *
      10(-3) mm(2)/s); the mean ADC values in endometrioma (1.387 * 10(-3) mm(2)/s)
      were significantly lower than in other cystic lesions (2.372 * 10(-3) mm(2)/s).
      CONCLUSION: Inclusion of MRI in the diagnostic algorithm of the indeterminate
      adnexal mass allows better differentiation of ovarian lesions resulting in a
      change of therapeutic decision-making with net cost savings.

PMID- 21174099
TI  - [Concomitant cellular reactions in optic nerve siderosis existing for 30 years].
AB  - Metal foreign bodies located in the optic nerve are a rare clinical picture and
      sooner or later often associated with vision loss. We report on a patient who had
      a foreign body in the optic nerve for 30 years. Histochemical analysis of the
      optic nerve after the requisite enucleation with complete functional loss of the
      eye revealed amazing results. Even 30 years after entry of the foreign body into
      the optic nerve neuronal structures with organized axons surrounded by
      cytoblasts, glial cells, and immunocompetent cells still remoined. These findings
      hold out hope and may serve as the starting point for regenerative medicine to
      potentially restore neuronal function.

PMID- 21174098
TI  - Intra-individual, randomised comparison of the MRI contrast agents gadobutrol and
      gadoterate in imaging the distal lower limb of patients with known or suspected
      osteomyelitis, evaluated in an off-site blinded read.
AB  - OBJECTIVE: To prove that 1.0 M gadobutrol provides superior contrast enhancement
      in suspicion of osteomyelitis of the feet compared with 0.5 M gadoterate.
      METHODS: MRI of feet was performed on 2 separate occasions. Independent
      injections of 1.0 M gadobutrol and 0.5 M gadoterate at doses of 0.1 mmol Gd/kg
      body weight were administered per patient. The interval between the two MR
      examinations was between 24 h and 7 days. Evaluation was performed in an off-site
      blinded read. RESULTS: 41 patients were eligible for efficacy analysis. Results
      of secondary efficacy variables did not show statistically significant
      differences. For the primary efficacy variable, a trend in favour of gadobutrol
      was seen in the full analysis set (ITT) population resulting in at least non
      inferiority. In the per protocol (PP) analysis set gadobutrol had better contrast
      than gadoterate (Wilcoxon signed rank test, p = 0.0466). CONCLUSION: Imaging of
      the distal lower limb in this special patient population requires a large number
      of patients to obtain enough comparative images where non-contrast-agent
      dependent factors do not disturb contrast agent efficacy. The ITT analysis showed
      at least non-inferiority of gadobutrol in comparison to gadoterate. The avoidance
      of imaging artefacts demonstrates a better outcome for gadobutrol.

PMID- 21174100
TI  - [Rebound tonometry and applanation tonometry during narcosis investigation of
      pediatric glaucoma].
AB  - BACKGROUND: A comparison of intraocular pressure (IOP) in cases of infantile
      glaucoma during general anesthesia was carried out by measurement with the iCare
      rebound tonometer (RBT) and a handheld applanation tonometer (Perkins). METHODS:
      A total of 45 eyes from pediatric patients with childhood glaucoma were included
      in this prospective trial. Bland-Altman plots and linear regression were used for
      statistical analysis. RESULTS: In almost two thirds of the eyes the difference
      between RBT and Perkins was 2 mmHg or less. A systemic bias of 1.96 mmHg and a
      95% confidence interval of -3.35 to 7.26 was detected. Linear regression of the
      Bland-Altman data showed a proportional error (gradient=0.16; r(2)=0.23; p<0.01).
      CONCLUSIONS: The iCare rebound tonometer is useful during general anesthesia in
      cases of childhood glaucoma. It provides comparable IOP values to applanation
      tonometry with a tendency to record higher values.

PMID- 21174101
TI  - [Restricted eyeball with proptosis].
AB  - Orbital cellulitis is an acute inflammation of the orbital content with
      exophthalmos, chemosis, blepharedema, reduction of eyeball motility and
      generalized illness, occasionally with fever. It is predominantly transmitted
      from the ENT region and rarely occurs as a complication after a scleral buckling
      procedure. The patient concerned contracted orbital cellulitis many years after
      scleral buckling because the cerclage was infected. Alterations to the sclera
      with atrophy and thinning in the context of myopia were probably favorable
      factors for development.

PMID- 21174103
TI  - Response to Vinchon.

PMID- 21174104
TI  - Qualitative and quantitative analysis of rectoanal inhibitory reflex (RAIR)
      modulation in functional bowel disorders.
AB  - BACKGROUND: Rectoanal inhibitory reflex (RAIR) is a physiological reflex
      implicated in anorectal continence. A lack of RAIR modulation is only described
      in spinal cord-injured patients with a lesion under L2. No quantitative data has
      been published concerning the normal modulation in amplitude and in duration in
      functional disorders. METHODS: A retrospective analysis of anorectal manometry,
      performed in 40 safe-neurological patients, suffering from idiopathic
      constipation and/or faecal incontinence, has been done. RAIR were obtained by
      five successive rectal distensions (10-50 ml).Resting pressure, residual
      pressure, percentages of relaxation, slope and duration of inhibition were
      estimated. Four hypotheses of normal modulation in amplitude and duration were
      set up using these parameters. The cut-off values chosen for the hypotheses were
      similar to results obtained by calculating median value +/- 2SD of the
      parameters. RESULTS: All the 40 patients had present RAIR. Concerning the
      modulation of RAIR, we tested the hypotheses with the aim of finding those
      applying to patient's largest number. Amplitude: 85% of the patients had a normal
      modulation defined by a difference >8 cm H2O between two non-consecutive residual
      pressure on three successive rectal distensions. DURATION: 77.5% of the patients
      had a normal modulation defined by a time difference >2 s between two non
      consecutive durations on three successive rectal distensions. CONCLUSION:
      Determination of normal values of RAIR modulation in functional disorders is
      interesting in clinical practise, suggesting that the patients with a lack of
      normal RAIR modulation (in amplitude or in duration) may have a neurological
      disease.

PMID- 21174105
TI  - Colonic bypass: an alternative approach to slow transit constipation in elderly
      patients.

PMID- 21174102
TI  - Chemical priming for spinal cord injury: a review of the literature part II
      potential therapeutics.
AB  - INTRODUCTION: Spinal cord injury is a complex cascade of reactions secondary to
      the initial mechanical trauma that puts into action the innate properties of the
      injured cells, the circulatory, inflammatory, and chemical status around them,
      into a non-permissive and destructive environment for neuronal function and
      regeneration. Priming means putting a cell, in a state of "arousal" towards
      better function. Priming can be mechanical as trauma is known to enhance activity
      in cells. MATERIALS AND METHODS: A comprehensive review of the literature was
      performed to better understand the possible chemical primers used for spinal cord
      injuries. CONCLUSIONS: Taken together, many studies have shown various promising
      results using the substances outlined herein for treating SCI.

PMID- 21174106
TI  - Sigmoid carcinoma presenting as epididymo-orchitis.

PMID- 21174107
TI  - Laparoscopic-assisted versus open surgery for rectal cancer: a meta-analysis of
      randomized controlled trials on oncologic adequacy of resection and long-term
      oncologic outcomes.
AB  - BACKGROUND: Whether laparoscopic-assisted surgery (LS) can achieve the same
      oncologic outcomes compared with open surgery (OS) for rectal cancer remains
      controversial. The aim of this meta-analysis of randomized controlled trials
      (RCTs) is to compare oncologic adequacy of resection and long-term oncologic
      outcomes of LS with OS in the treatment of rectal cancer. METHODS: Literature
      searches of electronic databases (Pubmed, Embase, Web of Science, and Cochrane
      Library) and manual searches were performed to identify RCTs comparing values of
      oncologic adequacy of resection, recurrence, and survival following LS and OS.
      RESULTS: Six RCTs enrolling 1,033 participants were included in the meta
      analysis. LS was associated with similar number of lymph nodes harvested and a
      similar distal tumor-free margin. LS was associated with a slightly high
      circumferential resection margin (CRM) positive rate with no significant
      difference (7.94% vs. 5.37%; risk ratio [RR], 1.13; P = 0.63). There was no
      significant difference between the two groups in local recurrence (RR, 0.55; P =
      0.21). The 3-year overall survival advantage for LS over OS was not statistically
      significantly different (hazard ratio [HR], 0.76; P = 0.11). The 3-year disease
      free survival was not significantly different between the two groups (HR, 1.16; P
      = 0.64). CONCLUSIONS: The meta-analysis suggests that there are no differences
      between laparoscopic-assisted and open surgery in terms of number of lymph nodes
      harvested, involvement of CRM, local recurrence, 3-year overall survival, and
      disease-free survival for rectal cancer. However, more high-quality studies are
      needed for further analysis due to the small number of included studies.

PMID- 21174108
TI  - Comparative toxicity of oxygenated monoterpenoids in experimental hydroalcoholic
      lotions to permethrin-resistant adult head lice.
AB  - The use of botanical compounds such as essential oils has recently become the
      subject of great interest as a natural means of pest control because of their
      ovicidal, larvicidal, or adulticidal activity against various insect species
      including head lice. We tested and compared the efficacy of pure oxygenated
      monoterpenoids that are main ingredients of essential oils of good biological
      activity. We used pulegone and citral, components of Aloysia citrodora, and
      geraniol, citronellol, and linalool, components of Geranium sp. oil. We found
      that citronellol and geraniol showed the highest knockdown and mortality effect
      (>60%) on adults of both sexes (50:50%) and third-stage nymphs. Pulegone,
      linalool, and citral showed knockdown percentages between 42 and 55%, and
      mortality percentages between 47 and 53%. A simple linear regression analysis
      showed statistically significant relationships between the studied toxic effects
      and viscosity of the monoterpenoids (p < 0.05), but not with their partition
      coefficient (log P).

PMID- 21174109
TI  - Dendritic cells: ultrastructural and immunophenotypical changes upon nb-UVB in
      vitiligo skin.
AB  - The role of dendritic cells in vitiligo is still unclear. Few studies have
      provided contradictory results about their quantitative variation and no data
      exist concerning their immunophenotypical distribution in diseased skin. The
      purpose of our study was to analyze the presence, the distribution, the
      immunophenotypical markers and the effects of nb-UVB therapy on dendritic cells
      in non-lesional, perilesional, and lesional vitiligo skin. Punch-biopsies of 6 mm
      were taken from lesional, perilesional, and non-lesional skin of 12 patients
      affected by non-segmental vitiligo, treated with nb-UVB. An immunohistochemical
      and an ultrastructural analysis were performed. Immunohistochemical and
      ultrastructural analysis showed both quantitative and qualitative modifications
      of Langerhans cells. Nb-UVB therapy, one of the most effective treatments for the
      disease, was able to reduce the Langerhans cells number and to redistribute main
      dendritic subsets. This study underlines the importance of dendritic cells,
      Langerhans cells in particular, in non-segmental vitiligo, in its pathogenesis
      and in its better therapeutical approach.

PMID- 21174110
TI  - Expressed and perceived emotion over time: does the patients' view matter for the
      caregivers' burden?
AB  - While the impact of mentally ill patients' perceptions of their key relatives'
      expressed emotion is well examined with regard to relapse, there is a paucity of
      evidence concerning the impact on their key relatives' burden. The present study
      aims to evaluate the relative prognostic value of expressed and perceived emotion
      on caregivers' stress outcome within a 3-year follow-up period. Yearly follow-up
      data of the key relatives of 16 first-hospitalized schizophrenic and 34 depressed
      patients were available including expressed and perceived emotion and different
      dimensions of caregivers' stress outcome: objective and subjective burden, well
      being, psychological symptoms and subjective quality of life. Multiple linear
      regression analyses were computed to assess the relative impact of expressed and
      perceived emotion. All dimensions of burden were significantly and consistently
      correlated with caregivers' expressed emotion and patients' perceived criticism
      on the bivariate level. On the multivariate level, however, expressed criticism
      appeared to be the most relevant predictor, followed by perceived resignation.
      Data indicate that the impact of the patients' perceived criticism on caregivers'
      stress outcome is limited. More attention should be paid to patients' perceived
      resignation which may be an unidentified stress contributor for caregivers so
      far.

PMID- 21174112
TI  - Assessment of small-airways disease using alveolar nitric oxide and impulse
      oscillometry in asthma and COPD.
AB  - The contribution of the alveolar compartment to exhaled nitric oxide (alveolar
      nitric oxide or CA(NO)) can be calculated as a surrogate of distal inflammation.
      This value should be corrected for nitric oxide produced in the conducting
      airways which "back-diffuses" into the alveolar compartment (Corrected CA(NO)).
      Impulse oscillometry (IOS) (Nava et al., Am J Respir Crit Care Med 168:1432-1437,
      2003) is used to derive values for peripheral airways resistance. Twenty-four
      healthy volunteers, 21 severe asthmatics, 15 mild-to-moderate asthmatics, and 24
      COPD patients were assessed with spirometry, impulse oscillometry, and
      fractionated exhaled nitric oxide. Compared to healthy volunteers, FE(NO) was
      higher in mild-to-moderate and severe asthmatics: geometric mean fold ratios of
      1.91 (P = 0.02) and 2.74 (P < 0.001), respectively. However, there was no
      difference for mild-to-moderate versus severe asthma. Ratios for CA(NO) were not
      different for severe asthma versus COPD, but both were elevated compared to that
      of healthy volunteers [2.64 (P < 0.001) and 3.07 (P < 0.001), respectively] and
      mild-to-moderate asthma [1.95 (P = 0.04) and 2.28 (P < 0.01)]. However, after
      correction for axial diffusion, Corrected CA(NO) was increased in COPD compared
      to severe asthma (geometric mean fold ratio 1.28, P = 0.04), mild-to-moderate
      asthma (1.34, P < 0.01), and healthy volunteers (1.28, P = 0.02), and there was
      no difference between other groups. R5 and RF were reduced in healthy volunteers
      versus mild-to-moderate asthma (P = 0.011 and P < 0.001 respectively), severe
      asthma (P = 0.002 and P < 0.001), and COPD (P < 0.001 and P < 0.001). Peripheral
      resistance (R5-R20) was not different for healthy versus mild-to-moderate asthma
      but was higher in severe asthma (P < 0.001) and COPD (P < 0.001). Correlations
      were observed between R5-R20 versus FEF(25-75) (r = 0.71, P < 0.01), CA(NO) (r =
      0.44, P < 0.01), and Corrected CA(NO) (r = 0.24, P < 0.01). CA(NO) and IOS
      provide additional information to traditional measures of spirometry and tidal
      nitric oxide. Previous data reporting elevated alveolar nitric oxide in severe
      asthma may reflect back-diffusion of nitric oxide from the conducting airways
      into the alveolar compartment. Corrected CA(NO) and IOS may prove to be useful
      noninvasive measurements of small-airways disease.

PMID- 21174111
TI  - Sleep quality, depression, and quality of life in patients with pulmonary
      hypertension.
AB  - Pulmonary hypertension is a disabling disease characterized by progressive
      functional worsening, right heart failure, and death. Although pulmonary
      hypertension has been associated with poor quality of life, sleep quality has not
      been investigated in pulmonary hypertension patients. This was a cross-sectional
      study in which patients (N = 40) were asked to complete standardized
      questionnaires to assess sleep quality [using Pittsburgh Sleep Quality Index
      (PSQI)], insomnia, sleepiness, dyspnea, depression, restless leg syndrome, and
      quality of life [using Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR)]
      during routine office visits. Baseline hemodynamics, pulmonary function tests,
      exercise capacity, and transthoracic echocardiogram were analyzed. Pulmonary
      hypertension functional class was World Health Organization class II [20 (50%)],
      III [18 (45%)], and IV [2 (5%)], and 29 (72.5%) had poor sleep quality. PSQI
      score was associated with CAMPHOR symptoms score (R = 0.61, P < 0.001), CAMPHOR
      activities score (R = 0.38, P = 0.016), CAMPHOR quality-of-life score (R = 0.45,
      P = 0.004), depression (R = 0.42, P = 0.007), and dyspnea (R = 0.36, P = 0.02).
      Sleep quality was not associated with age, gender, other comorbidities, pulmonary
      hypertension etiology, baseline hemodynamics, pulmonary function testing,
      echocardiographic parameters, or exercise capacity. Poor sleep quality is common
      in patients with pulmonary hypertension and correlates with depression, dyspnea,
      and poor quality of life. Improving sleep quality in patients with pulmonary
      hypertension may improve quality of life.

PMID- 21174113
TI  - Striatal 123I-Ioflupane SPECT abnormality in sporadic Creutzfeldt-Jakob disease.

PMID- 21174114
TI  - Long-term efficiency of intravenously administered immunoglobulin in anti-Yo
      syndrome with paraneoplastic cerebellar degeneration.

PMID- 21174115
TI  - Association between asymmetry in cataract and asymmetry in age-related macular
      degeneration. The Beijing Eye Study.
AB  - BACKGROUND: To examine in an intra-individual comparison whether cataract is
      associated with age-related macular degeneration (AMD). METHODS: The population
      based Beijing Eye Study included 4,439 subjects (age: 40+ years) out of 5,324
      subjects invited to be examined. Using lens and fundus photographs, the amount of
      AMD was graded according to the Wisconsin Age-Related Maculopathy Grading system
      and the degree of cataract was graded using the system of the Age-Related Eye
      Disease Study. RESULTS: Photographs with sufficient quality for bilateral
      examination of the lens and macula were available for 3,826 (86.2%) participants
      with a mean age of 55.3 +/- 10.0 years (range: 40-90 years) and a mean refractive
      error of -0.38 +/- 2.18 diopters (range: -20.13 diopters to +7.50 diopters). The
      side difference in presence of early AMD and late AMD respectively was not
      significantly associated with the inter-eye difference in the amount of nuclear
      cataract [P = 0.27 and P = 0.28 (r = 0.02) respectively), amount of cortical
      cataract (P = 0.12 and P = 0.05 respectively), and amount of subcapsular
      posterior cataract (P = 0.91 and P = 0.85 respectively). In a similar manner, the
      side difference in the presence of early AMD and late AMD was not significantly
      associated with the inter-eye difference in the presence of nuclear cataract (P =
      0.99 and P = 0.99 respectively), cortical cataract (P = 0.25 and P = 1.00
      respectively), and subcapsular posterior cataract (P = 0.59 and P = 0.05
      respectively). The side difference in the number of macular drusen was not
      significantly associated with the inter-eye difference in the amount of nuclear
      cataract (P = 0.74), amount of cortical cataract (P = 0.19) and amount of
      subcapsular posterior cataract (P = 0.88). As a corollary, unilateral
      pseudophakia or aphakia was not significantly associated with inter-eye
      differences in the count (P = 0.59) of drusen, and overall presence of early AMD
      (P = 0.99) or late AMD (P = 0.99). CONCLUSIONS: In an intra-individual, inter-eye
      comparison, avoiding interdependencies of systemic parameters, inter-eye
      difference was not significantly associated with any characteristics of age
      related macular degeneration in either any type of cataract or in pseudophakia.
      This suggests that the development of cataract or cataract surgery did not
      markedly influence the development of age-related macular degeneration.

PMID- 21174116
TI  - In vitro culture of human fetal corneal endothelial cells.
AB  - PURPOSE: To explore and optimize a proper culture system for human fetal corneal
      endothelial cells (hFCECs), including the methods of primary culture, passage and
      cryopreservation. METHODS: Fresh fetal corneas were explanted to propagate
      primary corneal endothelial cells. The cells were cultured in DMEM/F-12
      supplemented with 10% fetal bovine serum (FBS) in the absence or presence of the
      extracts from bovine corneal endothelium cells (bCECs), and the cells were
      identified with immunocytochemical staining. The passage and cryopreservation of
      hFCECs were optimized according to previous reports on adult corneal endothelial
      cells. RESULTS: Using the explant culture method, hFCECs migrated successfully
      within 3 days and assumed polygonal-shaped corneal endothelial morphology. The
      optimizing methods were 0.125% trypsin + 0.02% EDTA for passage and 10% DMSO +
      90% FBS for cryopreservation. Recovered hFCECs from cryopreservation remained
      typical morphology and immunological markers of corneal endothelial cells,
      including positive staining of NSE, Nestin, Ki67 and ZO-1, and negative staining
      of CK3/12, which demonstrated that they retained the characterizations of corneal
      endothelial cells and proliferative capacity. Moreover, the extracts from bCECs
      can promote the proliferative capacity of hFCECs significantly, while maintaining
      their typical endothelial morphology. CONCLUSIONS: The culture conditions of
      human fetal corneal endothelial cells were firstly optimized, including the
      primary culture, passage and cryopreservation. Meanwhile, we confirmed that the
      extracts from bovine corneal endothelium promoted the proliferative capacity
      while maintaining the morphology of hFCECs in vitro.

PMID- 21174117
TI  - Usefulness of liquid-based cytology in hormone receptor analysis of breast cancer
      specimens.
AB  - Immunohistochemical (IHC) analysis of the hormone receptor (HR) in breast cancer
      cytology is an important issue nowadays. Several studies have shown discrepancy
      in the HR status between the primary tumor and metastases. Cytology can be used
      for patients with metastatic disease. Although cytological assessment of HR is an
      excellent method, it has not been routinely used because of the difficulty in
      consistently preparing multiple good quality slides. Liquid-based cytology (LBC)
      preparation is considered as the key to resolving the aforementioned problem;
      however, few studies have reported the HR assessment in breast cancer using LBC.
      Therefore, the HR status of LBC slides from 82 breast cancers was compared with
      that of the corresponding surgical specimens. The HR assay in both the LBC slides
      and surgical specimens was conducted by IHC using an autostainer. For the IHC
      staining, the protocol recommended by the manufacturer for paraffin-embedded
      sections was used for both the cytology and histology specimens. The HR results
      of the cytology agreed with those of the histology in 80 of the 82 cases
      (accuracy rate, 98%) for estrogen receptor, and in 78 of the 82 cases (accuracy
      rate, 95%) for progesterone receptor. The overall accuracy of the HR status on
      the cytology and the histology was 99% in 81 of the 82 cases. In conclusion, in
      HR analysis of breast cancers, LBC followed by IHC using an autostainer was
      useful for the standard processing of cytological specimens and showed a good
      correlation with the results of analysis on the histology specimens.

PMID- 21174119
TI  - Relevant factors influencing flatfoot in preschool-aged children.
AB  - The aim of this study was to discuss the influence of age, gender, obesity
      status, joint laxity, and the W-sitting habit on flatfoot in preschool-aged
      children. A total of 1,598 children (833 boys and 765 girls) between 3 and 6
      years of age from kindergartens in the central area of Taiwan were studied. The
      children were divided into a normal group (n = 733), a unilateral flatfoot group
      (n = 266), and a bilateral flatfoot group (n = 599), and a multinomial logistic
      regression model was used to analyze the data. The prevalence of flatfoot
      decreased significantly with increasing age: 54.5% of 3-year-old but only 21% for
      6-year-old children had bilateral flatfoot. In the bilateral flatfoot group, the
      risk decreased with increased age, increased with increasing weight beyond the
      normal range, and was higher for boys than girls. Age and obesity status were not
      significantly influential in the unilateral flatfoot group. Children with higher
      joint laxity and a habit of W-sitting also experienced higher risk in both
      flatfoot groups. In conclusion, this study demonstrates a significant association
      of age, gender, obesity status, joint laxity, and the W-sitting habit with the
      bilateral flatfoot in preschool-aged children. Children with unilateral flatfoot
      differ from those with normal feet and bilateral flatfoot. It is suggested that
      the unilateral flatfoot deserves special attention in future studies.

PMID- 21174118
TI  - Therapy of experimental influenza virus infection with pyrrolidine
      dithiocarbamate.
AB  - The search for new antiviral strategies to treat influenza A virus (IAV)
      infections is one major international health care activity. Hereby, the IAV
      caused misuse of cellular nuclear factor kappa B (NF-kappaB) signaling pathways
      in infected cells represents one target for antiviral therapy. In the present
      study, pyrrolidine dithiocarbamate (PDTC), which is known as an antioxidant and
      as an inhibitor of IAV-induced NF-kappaB activation, was studied in vivo. After
      the antiviral activity of PDTC was confirmed in MDCK cells, mice-infected with
      the mouse-adapted strain of IAV A/PR/8/34 (H1N1)-were treated intraperitoneally
      simultaneously with PDTC (75, 150, 200 mg/kg body weight). The influence of PDTC
      administrations was evaluated on viral replication and inflammatory reactions in
      lung tissue up to 14 days postinfection (p. i.). This therapy increased survival
      up to 80% and reduced IAV-caused weight loss and viral replication in lung tissue
      in a dose-dependent manner. Protective effects were less pronounced, if the
      therapy started later on during an ongoing IAV infection. In addition,
      simultaneous PDTC treatment also limited IAV-caused infiltration of immune cells
      as well as local interferon-gamma expression in lung tissue. These results imply
      that PDTC decreases IAV-caused disease in mice significantly. Therefore, the
      development of drugs like PDTC that interfere with NF-kappaB signaling may
      represent a modern focus of anti-IAV therapy.

PMID- 21174120
TI  - The impact of prophylaxis on paediatric intensive care unit admissions for RSV
      infection: a retrospective, single-centre study.
AB  - Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract
      infections and hospitalizations in children aged < 2 years. The aim of this
      retrospective, single-centre study was to examine the characteristics of patients
      admitted to a paediatric intensive care unit (PICU) with RSV infection following
      the implementation of a RSV prophylaxis programme. Electronic hospital medical
      records of all PICU admissions for RSV infection were searched from 2003 to 2009.
      Data on baseline demographics, underlying disease, criteria for hospitalization,
      respiratory diagnosis and management, complications and palivizumab prophylaxis
      were collected. A total of 181 patients were admitted with RSV infection,
      accounting for 5.7% of all admissions. Eighty-four percent were <= 2 years of
      age. Majority (70.2%) had no underlying medical illness, and 79.6% received
      antibiotics as part of their medical treatment. Comparison of children aged <= 2
      years and those >2 years revealed that fewer of the younger cohort (20.4% versus
      79.3%; p < 0.001) had an underlying medical condition. RSV infection occurred in
      3.3% (n = 6) children who had received palivizumab prophylaxis, and there were
      two deaths. The results indicate that > 88% of all PICU admissions would not
      qualify for RSV prophylaxis under our established guidelines and 66% of the
      children aged <= 2 years were > 36 weeks gestation and are not currently targeted
      for prophylaxis. The number of high-risk infants admitted to PICU with RSV
      infection has likely plateaued, and further reductions in admission rates may
      only be realised with the use of universal, vaccine immunization programmes.

PMID- 21174121
TI  - Low and high birth weight as risk factors for obesity among 4 to 5-year-old
      Australian children: does gender matter?
AB  - Studies testing whether birth weight and childhood obesity differ by gender are
      lacking. We aimed to describe the relationship between birth weight and childhood
      overweight/obesity and investigate the influence that gender has on this
      relationship among 4 to 5-year-old children. We performed a secondary analysis of
      an Australian nationally representative cross-sectional study in 4 to 5-year-old
      children. The main outcome measure was child overweight and obesity. We found
      that low birth weight (LBW) was associated with lower risk of overweight/obesity
      among girls at 4-5 years before (OR 0.50, 95%CI 0.32, 0.77) and after adjusting
      for socio-demographic factors (OR 0.51 95% CI 0.33, 0.80) and ethnicity (OR 0.52,
      95%CI 0.33, 0.81) but was not associated with child overweight/obesity among boys
      before or after adjustment. High birth weight (HBW) was associated with a higher
      risk of overweight/obesity among both girls (adjusted OR: 1.76, 95% CI 1.12,
      2.78) and boys (adjusted OR: 2.42 95% CI 2.06, 2.86). CONCLUSION: There are
      gender differences in the association of birth weight with child
      overweight/obesity. HBW was associated with a higher risk of child
      overweight/obesity in boys and girls before and after adjustment for socio
      demographic factors. However, LBW was associated with a lower risk of child
      overweight/obesity in girls but not in boys. These gender differences need to be
      considered when planning interventions to reduce child overweight/obesity.

PMID- 21174123
TI  - Transition from pediatric to adult health care: expectations of adolescents with
      chronic disorders and their parents.
AB  - The aim of this study was to assess the expectations of adolescents with chronic
      disorders with regard to transition from pediatric to adult health care and to
      compare them with the expectations of their parents. A cross-sectional study was
      carried out including 283 adolescents with chronic disorders, aged 14-25 years
      (median age, 16.0 years), and not yet transferred to adult health care, and their
      318 parents from two university children's hospitals. The majority of adolescents
      and parents (64%/70%) perceived the ages of 18-19 years and older as the best
      time to transfer to adult health care. Chronological age and feeling too old to
      see a pediatrician were reported as the most important decision factors for the
      transfer while the severity of the disease was not considered important. The most
      relevant barriers were feeling at ease with the pediatrician (45%/38%), anxiety
      (20%/24%), and lack of information about the adult specialist and health care
      (18%/27%). Of the 51% of adolescents with whom the pediatric specialist had
      spoken about the transfer, 53% of adolescents and 69% of parents preferred a
      joint transfer meeting with the pediatric and adult specialist, and 24% of these
      adolescents declared that their health professional had offered this option. In
      summary, the age preference for adolescents with chronic disorders and their
      parents to transfer to adult health care was higher than the upper age limits for
      admission to pediatric health care in many European countries. Anxiety and a lack
      of information of both adolescents and their parents were among the most
      important barriers for a smooth and timely transfer according to adolescents and
      parents.

PMID- 21174124
TI  - A novel wide-field neuron with branches in the lamina of the Drosophila visual
      system expresses myoinhibitory peptide and may be associated with the clock.
AB  - Although neuropeptides are widespread throughout the central nervous system of
      the fruifly Drosophila, no records exist of peptidergic neurons in the first
      synaptic region of the visual system, the lamina. Here, we describe a novel type
      of neuron that has wide-field tangential arborizations just distal to the lamina
      neuropil and that expresses myoinhibitory peptide (MIP). The cell bodies of these
      neurons, designated lateral MIP-immunoreactive optic lobe (LMIo) neurons, lie
      anteriorly at the base of the medulla of the optic lobe. The LMIo neurons also
      arborize in several layers of the medulla and in the dorso-lateral and lateral
      protocerebrum. Since the LMIo resemble LN(v) clock neurons, we have investigated
      the relationships between these two sets of neurons by combining MIP
      immunolabeling with markers for two of the clock genes, viz., Cryptochrome and
      Timeless, or with antisera to two peptides expressed in clock neurons, viz.,
      pigment-dispersing factor and ion transport peptide. LMIo neurons do not co
      express any of these clock neuron markers. However, branches of LMIo and clock
      neurons overlap in several regions. Furthermore, the varicose lamina branches of
      LMIo neurons superimpose those of two large bilateral serotonergic neurons. The
      close apposition of the terminations of MIP- and serotonin-producing neurons
      distal to the lamina suggests that they have the same peripheral targets. Our
      data indicate that the LMIo neurons are not bona fide clock neurons, but they may
      be associated with the clock system and regulate signaling peripherally in the
      visual system.

PMID- 21174125
TI  - Telocytes in pleura: two- and three-dimensional imaging by transmission electron
      microscopy.
AB  - Information about the ultrastructure of connective (interstitial) cells
      supporting the pleural mesothelium is scarce. Our aim has been to examine whether
      telocytes (TCs) are present in pleura, as in epicardium and mesentery. TCs are a
      distinct type of cell, characterized by specific prolongations named telopodes
      (Tp). We have used transmission electron microscopy (TEM) and electron tomography
      (ET) to determine whether ultrastructural diagnostic criteria accepted for TCs
      are fulfilled by any of the cell subpopulations existing in the sub-mesothelial
      layer in mouse and human pleura. TCs have been identified with TEM by their
      characteristic prolongations. Tp appear long and moniliform, because of the
      alternation of podomeres (thin segments of less than 0.2 MUm) and podoms (small
      dilations accommodating caveolae, mitochondria, and endoplasmic reticulum). Tp
      ramifications follow a dichotomic pattern and establish specialized cell-to-cell
      junctional complexes. TCs, via their Tp, seem to form an interstitial network
      beneath the mesothelium, covering about two-thirds of the abluminal mesothelial
      layer. ET has revealed complex junctional structures and tight junctions
      connecting pleural TCs, and small vesicles at this level in Tp. Thus, pleural TCs
      share significant similarities with TCs described in other serosae. Whether TCs
      are a (major) player in mesothelial-cell-induced tissue repair remains to be
      established. Nevertheless, the extremely long thin Tp and complex junctional
      structures that they form and the release of vesicles (or exosomes) indicate the
      participation of TCs in long-distance homo- or heterocellular communication.

PMID- 21174127
TI  - Tree rings of Scots pine (Pinus sylvestris L.) as a source of information about
      past climate in northern Poland.
AB  - Scots pine (Pinus sylvestris) is a very common tree in Polish forests, and
      therefore was widely used as timber. A relatively large amount of available wood
      allowed a long-term chronology to be built up and used as a source of information
      about past climate. The analysis of reconstructed indexed values of mean
      temperature in 51-year moving intervals allowed the recognition of the coldest
      periods in the years 1207-1346, 1383-1425, 1455-1482, 1533-1574, 1627-1646, and
      1694-1785. The analysis of extreme wide and narrow rings forms a complementary
      method of examining climatic data within tree rings. The tree ring widths, early
      wood and late wood widths of 16 samples were assessed during the period 1581
      1676. The most apparent effect is noted in the dry summer of 1616. According to
      previous research and our findings, temperature from February to March seems to
      be one of the most stable climatic factors which influenced pine growth in
      Poland. Correlation coefficients in the calibration and validation procedure gave
      promising results for temperature reconstruction from the pine chronology.

PMID- 21174129
TI  - Predictors of adherence to a behavioral therapy sleep intervention during breast
      cancer chemotherapy.
AB  - BACKGROUND: This study's purpose was twofold: (1) to establish adherence rates to
      a behavioral therapy (BT) sleep intervention and (2) to identify psychological
      and physical symptom predictors of adherence to the intervention in women
      undergoing breast cancer chemotherapy. METHODS: A randomized controlled trial
      began 48 h before the first of four chemotherapy treatments. Women with stages I
      IIIA breast cancer (n = 113) received a BT sleep intervention composed of
      stimulus control, modified sleep restriction (MSR), relaxation therapy (RT), and
      sleep hygiene counseling components. A BT plan was developed by a research nurse
      and each participant, reinforced on day 8, and repeated for chemotherapy cycles
      2, 3, and 4. Adherence to the BT plan was measured daily; total adherence score
      was computed at each chemotherapy cycle by combining adherence estimates of all
      BT plan components. Psychological and physical symptoms over the past 7 days were
      measured 2 days prior to and 7 days after each chemotherapy treatment. RESULTS:
      Total adherence rates to the BT plan were 51-52% at all four treatments but
      adherence varied by component. Sleep disturbance, pain, and anxiety significantly
      decreased whereas depression significantly increased across chemotherapy.
      Structural equation modeling revealed a good model fit with decreasing sleep
      disturbances (0.409) and increasing depression (-0.711) contributing to lower
      total adherence rates. Increasing depression predicted lower MSR adherence (
      0.203) and decreasing sleep disturbances predicted lower RT adherence (1.220).
      CONCLUSIONS: Sleep disturbance and depression significantly impacted adherence
      rates during chemotherapy. Results warrant attention when promoting adherence to
      BT sleep interventions during chemotherapy treatment.

PMID- 21174130
TI  - Vasculature and neurovascular relationships of the trigeminal nerve root.
AB  - BACKGROUND: Specific microanatomical characteristics of the trigeminal nerve root
      (TNR) blood supply and close neurovascular relationships with surrounding vessels
      as well as their possible clinical significance were the main reasons for this
      study. METHOD: The vasculature of 25 adult and four fetal TNRs were
      microdissected and examined under the stereoscopic microscope, after injecting
      their arteries with India ink. RESULTS: The trigeminal vessels, which varied
      between two and five in number, arose from two or three of the following
      arteries: the superolateral pontine (92%), anterior inferior cerebellar (AICA)
      (88%), inferolateral pontine (72%), and superior cerebellar (SCA) (12%). The
      trigeminal vascular twigs had a mean diameter of 0.215 mm. A single vessel may
      supply either the motor portion of the nerve root or the sensory portion or both.
      The trigeminal vasculature formed the proximal and distal rings. The proximal
      ring was located at the trigeminal root entry zone. Its central branches extended
      along the TNR to the principal sensory and motor trigeminal nuclei while its
      peripheral longitudinal twigs followed the TNR fascicles. The incomplete distal
      arterial ring embraced the middle portion of the TNR before the level of its
      entrance into the arachnoid sleeve. The most frequent contact of the TNR was
      noticed with the SCA (20%), the petrosal or Dandy's vein (24%), and the AICA
      (12%). CONCLUSIONS: The observed characteristics of the TNR vasculature could be
      the anatomical basis for decompressive neurovascular surgery.

PMID- 21174128
TI  - Evolution of reproductive development in the volvocine algae.
AB  - The evolution of multicellularity, the separation of germline cells from sterile
      somatic cells, and the generation of a male-female dichotomy are certainly among
      the greatest innovations of eukaryotes. Remarkably, phylogenetic analysis
      suggests that the shift from simple to complex, differentiated multicellularity
      was not a unique progression in the evolution of life, but in fact a quite
      frequent event. The spheroidal green alga Volvox and its close relatives, the
      volvocine algae, span the full range of organizational complexity, from
      unicellular and colonial genera to multicellular genera with a full germ-soma
      division of labor and male-female dichotomy; thus, these algae are ideal model
      organisms for addressing fundamental issues related to the transition to
      multicellularity and for discovering universal rules that characterize this
      transition. Of all living species, Volvox carteri represents the simplest version
      of an immortal germline producing specialized somatic cells. This cellular
      specialization involved the emergence of mortality and the production of the
      first dead ancestors in the evolution of this lineage. Volvocine algae therefore
      exemplify the evolution of cellular cooperation from cellular autonomy. They also
      serve as a prime example of the evolution of complex traits by a few successive,
      small steps. Thus, we learn from volvocine algae that the evolutionary transition
      to complex, multicellular life is probably much easier to achieve than is
      commonly believed.

PMID- 21174131
TI  - In silico prediction of drug targets in Vibrio cholerae.
AB  - Identification of potential drug targets is the first step in the process of
      modern drug discovery, subjected to their validation and drug development. Whole
      genome sequences of a number of organisms allow prediction of potential drug
      targets using sequence comparison approaches. Here, we present a subtractive
      approach exploiting the knowledge of global gene expression along with sequence
      comparisons to predict the potential drug targets more efficiently. Based on the
      knowledge of 155 known virulence and their coexpressed genes mined from
      microarray database in the public domain, 357 coexpressed probable virulence
      genes for Vibrio cholerae were predicted. Based on screening of Database of
      Essential Genes using blastn, a total of 102 genes out of these 357 were enlisted
      as vitally essential genes, and hence good putative drug targets. As the
      effective drug target is a protein which is only present in the pathogen,
      similarity search of these 102 essential genes against human genome sequence led
      to subtraction of 66 genes, thus leaving behind a subset of 36 genes whose
      products have been called as potential drug targets. The gene ontology analysis
      using Blast2GO of these 36 genes revealed their roles in important metabolic
      pathways of V. cholerae or on the surface of the pathogen. Thus, we propose that
      the products of these genes be evaluated as target sites of drugs against V.
      cholerae in future investigations.

PMID- 21174133
TI  - New insight into the formation mechanism of imidazolium-based halide salts.
AB  - By performing density functional theory calculations, the Menshutkin reaction
      between the N-methyl imidazole with chloroethane is reexamined to rationalize the
      experimental discovery. The calculated results show that the reaction proceeds
      via a S(N)2 mechanism with a barrier of 119.1 kJ mol(-1) which is much lower than
      that reported in previous literature according to a five-membered transition
      state mechanism. Moreover, it is found that the barrier is further reduced to
      98.1 kJ mol(-1) in toluene solution. The present result validates the
      experimental finding that the Menshutkin reaction for synthesizing N-alkyl
      imidazolium halide salts proceed smoothly at lower heating temperature.

PMID- 21174132
TI  - Plasmodesmata during development: re-examination of the importance of primary,
      secondary, and branched plasmodesmata structure versus function.
AB  - Plasmodesmata (PD) structure and function vary temporally and spatially during
      all stages of plant development. PD that originate during, or post, cell division
      are designated as primary or secondary according to classical terminology. PD
      structure may be simple, twinned, or branched. Studies of PD during leaf, root,
      and embryo development have lead to the generalization that cells in less mature
      tissues contain predominantly simple PD. New quantitative analyses reveal that
      twinned and branched PD also occur in immature tissues. New data also highlight
      the versatility of viral movement proteins as tags for labeling PD in immature
      tissues as well as PD in mature tissues. A summary of the formation and function
      of primary, secondary, and branched PD during leaf, trichome, embryo, apical
      meristem, vascular cambium, and root development underscores the remarkable and
      indispensible plant-specific intercellular communication system that is mediated
      by PD.

PMID- 21174134
TI  - Can molecular dynamics simulations assist in design of specific inhibitors and
      imaging agents of amyloid aggregation? Structure, stability and free energy
      predictions for amyloid oligomers of VQIVYK, MVGGVV and LYQLEN.
AB  - The aggregation modes of hexapeptide fragments of Tau, Insulin and Abeta peptide
      (VQIVYK, MVGGVV and LYQLEN) were found from their microcrystalline structures
      that had been recently resolved by X-ray analysis. The atomic structures reveal a
      dry self-complementary interface between the neighboring beta-sheet layers,
      termed "steric zipper". In this study we perform several all-atom molecular
      dynamics simulations with explicit water to analyze stability of the crystalline
      fragments of 2-10 hexapeptides each and their analogs with single glycine
      replacement mutations to investigate the structural stability, aggregation
      behavior and thermodynamic of the amyloid oligomers. Upon comparing single and
      double layer models, our results reveal that additional strands contribute
      significantly to the structural stability of the peptide oligomers for double
      layer model, while in the case of single layer model the stability decreases (or
      remains the same in the case of LYQLEN). This is in agreement with the previous
      studies performed on different types of amyloid models. We also replaced the side
      chains participating in the steric zipper interfaces with glycine. None of the
      mutants were structurally stable compared to the respective wild type model,
      except for mutants V2G and V6G in MVGGVV2 case. The exception can be explained by
      structural features of this particular polymorph. The double layer decamer and
      dodecamer aggregates of the wild type hexapeptides appear to be stable at 300K,
      which is confirmed by the conservation of high anti-parallel beta-sheet content
      throughout the whole simulation time. Deletions of the side chains resulted in
      decline of secondary structure content compared to corresponding wild type
      indicating that the role of the replaced amino acid in stabilizing the structure.
      Detailed analysis of the binding energy reveals that stability of these peptide
      aggregates is determined mainly by the van der Waals and hydrophobic forces that
      can serve as quantitative measure of shape complementarities between the side
      chains. This observation implies that interactions among side chains forming the
      dehydrated steric zipper, rather than among those exposed to water, are the major
      structural determinant. The electrostatic repulsion destabilizes the studied
      double layer aggregates in two cases, while stabilizes the other two. Negative
      total binding free energy indicates that both wild type and mutants complex
      formation is favorable. However, the mutants complexation is less favorable than
      the wild type's. The present study provides the atomic level understanding of the
      aggregation behavior and the driving force for the amyloid aggregates, and could
      be useful for rational design of amyloid inhibitors and amyloid-specific
      biomarkers for diagnostic purposes.

PMID- 21174135
TI  - FTIR, Raman, and UV-Vis spectroscopic and DFT investigations of the structure of
      iron-lead-tellurate glasses.
AB  - In this work, the effects of iron ion intercalations on lead-tellurate glasses
      were investigated via FTIR, Raman and UV-Vis spectroscopies. This homogeneous
      glass system has compositions xFe(2)O(3).(100-x)[4TeO(2).PbO(2)], where x = 0-60
      mol%. The presented observations in these mechanisms show that the lead ions have
      a pronounced affinity towards [TeO(3)] structural units, resulting in the
      deformation of the Te-O-Te linkages, and leading to the intercalation of [PbO( n
      )] (n = 3, 4) and [FeO( n )] (n = 4, 6) entities in the [TeO(4)] chain network.
      The formation of negatively charged [FeO(4)](1-) structural units implies the
      attraction of Pb(2+) ions in order to compensate for this electrical charge. Upon
      increasing the Fe(2)O(3) content to 60 mol%, the network can accommodate an
      excess of oxygen through the formation of [FeO(6)] structural units and the
      conversion of [TeO(4)] into [TeO(3)] structural units. For even higher Fe(2)O(3)
      contents, Raman spectra indicate a greater degree of depolymerization of the
      vitreous network than FTIR spectra do. The bands due to the Pb-O bond vibrations
      are very strongly polarized and the [TeO(4)] structural units convert into
      [TeO(3)] units via an intermediate coordination stage termed "[TeO(3+1)]"
      structural units. Our UV-Vis spectroscopic data show two mechanisms: (i) the
      conversion of the Fe(3+) to Fe(2+) at the same time as the oxidation of Pb(2+) to
      Pb(+4) ions for samples with low Fe(2)O(3) contents; (ii) when the Fe(2)O(3)
      content is high (x >= 50 mol%), the Fe(2+) ions capture positive holes and are
      transferred to Fe(3+) ions through a photochemical reaction, while the Pb(2+)
      ions are formed by the reduction of Pb(4+) ions. DFT calculations show that the
      addition of Fe(2)O(3) to lead-tellurate glasses seems to break the axial Te-O
      bonds, and the [TeO(4)] structural units are gradually transformed into
      [TeO(3+1)]- and [TeO(3)]-type polyhedra. Analyzing these data further indicates a
      gradual conversion of the lead ions from covalent to ionic environment. There is
      then a charge transfer between the tri- and tetracoordinated tellurium atoms due
      to the capacity of the lead-tellurate network to form the appropriate
      coordination environments containing structural units of opposite charge, such as
      iron ions, [FeO(4)](1-).

PMID- 21174136
TI  - Development of a QSPR model for predicting thermal stabilities of nitroaromatic
      compounds taking into account their decomposition mechanisms.
AB  - The molecular structures of 77 nitroaromatic compounds have been correlated to
      their thermal stabilities by combining the quantitative structure-property
      relationship (QSPR) method with density functional theory (DFT). More than 300
      descriptors (constitutional, topological, geometrical and quantum chemical) have
      been calculated, and multilinear regressions have been performed to find accurate
      quantitative relationships with experimental heats of decomposition (-DeltaH). In
      particular, this work demonstrates the importance of accounting for chemical
      mechanisms during the selection of an adequate experimental data set. A reliable
      QSPR model that presents a strong correlation with experimental data for both the
      training and the validation molecular sets (R (2) = 0.90 and 0.84, respectively)
      was developed for non-ortho-substituted nitroaromatic compounds. Moreover, its
      applicability domain was determined, and the model's predictivity reached 0.86
      within this applicability domain. To our knowledge, this work has produced the
      first QSPR model, developed according to the OECD principles of regulatory
      acceptability, for predicting the thermal stabilities of energetic compounds.

PMID- 21174137
TI  - Hydroxyurea enhances SMN2 gene expression through nitric oxide release.
AB  - Small molecules that increase full-length survivor motor neuron (SMN) gene
      transcript are promising therapeutic candidates for spinal muscular atrophy
      (SMA). Hydroxyurea (HU) has recently been shown to increase full-length SMN
      transcript in cultured lymphocytes from patients with SMA. We investigate the
      mechanism by which HU enhances full-length SMN2 gene expression in SMA
      lymphocytes. Nitric oxide (NO) is a major intracellular metabolite of HU. We test
      whether NO donors can themselves enhance full-length SMN2 expression. Eighteen
      cell lines (five type I, five type II, six type III SMA, and two non-SMA
      controls) were treated with or without NO donors for 48 h. SMA cells treated with
      HU and three NO donors: two long-acting donors, Deta-NONOate and S
      nitrosoglutathione, and one short-acting donor, 3-ethyl-3-(ethylaminoethyl)-1
      hydroxy-2-oxo-1-triazene, resulted in significant increase in full-length SMN2
      mRNA. These effects were abolished by co-treatment with an NO scavenger 2-phenyl
      4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide. One short-acting NO donor, S
      nitroso-N-acetyl-DL-penicillamine, failed to show significant effect on full
      length SMN2 expression, possibly due to high degree of cytotoxicity. These
      results were observed using both densitometry and quantitative PCR methods. We
      conclude that HU enhances SMN2 expression through the release of NO. NO donors
      may themselves be considered as new therapeutic candidates for SMA.

PMID- 21174138
TI  - Parkinson's disease in China.
AB  - Paralysis agitans was first documented in 1817 by James Parkinson, and therefore
      the syndrome was named Parkinson's disease (PD). In fact, as early as more than
      2000 years ago, the clinical manifestations of this disease have been described
      in Chinese medicine classics, such as the "Huangdi Neijing (Yellow Emperor's
      Internal Classic)" and "Zhong Zang Jing (Hua's Zhong Zang Classic)." In recent
      years, especially in the past 30 years after reform and opening-up, PD has drawn
      a lot of attention by Chinese scholars. Although great progress in the studies of
      PD has been made in recent years, the gap between China and western countries
      still exists. In this review, we concentrate on the main progress made in
      epidemic characteristics, etiology, diagnosis and management of PD in China.

PMID- 21174139
TI  - Dementia in life writing: our health care system in the words of the sufferer.
AB  - Alzheimer's disease as the most common neurodegenerative disorder places enormous
      financial demands on our society that is increasingly focussed on the cost
      effectiveness of treatment and care. The present article reflects on central
      information drawn from four autobiographical texts written by patients in the
      early stage of dementia, elucidating their needs relating to, first, the
      medication they rely on and, second, the importance of a healthy doctor-patient
      relationship. Their comments and feelings are placed in the context of clinical
      practice and current health care policy pertaining to our dealing with dementia,
      thus, contributing to ongoing discussions relating to the suitability of current
      health care structures in view of challenging demographic changes.

PMID- 21174140
TI  - Clinical efficacy of levofloxacin 500 mg once daily for 7 days for patients with
      non-gonococcal urethritis.
AB  - To confirm the efficacy of the treatment regimen with oral levofloxacin (LVFX)
      500 mg once daily for 7 days for patients with non-gonococcal urethritis (NGU),
      we evaluated the microbiological and clinical outcomes of the regimen in those
      patients. We finally evaluated 53 patients with symptomatic NGU and 5 patients
      with asymptomatic NGU. As a result of microbiological examinations, 19 of the
      symptomatic patients were diagnosed as having non-gonococcal chlamydial
      urethritis (NGCU); 13 had non-gonococcal non-chlamydial urethritis (NGNCU), and
      21 had urethritis without any microbial detection. Five of the asymptomatic
      patients were diagnosed as having NGCU. Microbiological cure was achieved in 91%
      of the 32 patients with symptomatic NGU and in 80% of the 5 patients with
      asymptomatic NGCU. Clinical cure was obtained in 92% of the 53 patients with
      symptomatic NGU. The microbiological eradication rate for Chlamydia trachomatis
      was 92% in 24 patients. As for other organisms, the microbiological eradication
      rate for Mycoplasma genitalium was 60% in 5 patients and that for Ureaplasma
      urealyticum was 100% in 10. The microbiological and clinical efficacy of oral
      LVFX 500 mg once daily for 7 days for the patients with NGU was the same for the
      azithromycin (AZM) 1,000 mg single dose that we previously reported. The
      eradication rates of C. trachomatis and U. urealyticum in the treatment regimen
      with LVFX 500 mg were high enough in the clinical setting; however, for M.
      genitalium, the rate was relatively inferior to that with AZM.

PMID- 21174141
TI  - Clinical features of the 2009 swine-origin influenza A (H1N1) outbreak in Japan.
AB  - To clarify the clinical symptoms of the influenza A virus during the 2009
      pandemic influenza outbreak, we describe the clinical features of outpatients
      diagnosed with type A influenza by use of the rapid influenza diagnostic test
      (RIDT) from September to December 2009. Questionnaires were used to collect
      prospective data on 1,122 cases with influenza-like illness at our medical
      institutions. The independent predictors of influenza A virus were identified on
      the basis of demographic features and the clinical symptoms of the patients who
      tested positive for influenza A virus in the RIDT test. Of the 1,122 cases
      tested, 389 (34.7%) were positive for the influenza A virus. The median age of
      the influenza-positive patients was 14, and 58.9% of the patients were male. The
      symptoms fever, cough, rhinorrhea, and headache were statistically dominant. A
      history of recent contact with persons suffering from influenza or influenza-like
      illness at home, school, or in the workplace was significantly more common in the
      positive group than in the negative group. Pneumonia was observed in 2 (0.5%) of
      the positive patients, but the symptoms were only severe enough to require
      hospitalization in 1 of the 2. No deaths were observed among the 389 RIDT
      positive patients. Although the spread of influenza A virus was both rapid and
      extensive, mainly among children under the age of 18, it seemed to be mild.
      Appropriate interpretation of the RIDT on the basis of recent clinical
      information, and early treatment with antiviral drugs might help to prevent
      severe illness from influenza pandemics in the future.

PMID- 21174142
TI  - The nationwide study of bacterial pathogens associated with urinary tract
      infections conducted by the Japanese Society of Chemotherapy.
AB  - This study was conducted by the Japanese Society of Chemotherapy and is the first
      nationwide study on bacterial pathogens isolated from patients with urinary tract
      infections at 28 hospitals throughout Japan between January 2008 and June 2008. A
      total of 688 bacterial strains were isolated from adult patients with urinary
      tract infections. The strains investigated in this study are as follows:
      Enterococcus faecalis (n = 140), Escherichia coli (n = 255), Klebsiella
      pneumoniae (n = 93), Proteus mirabilis (n = 42), Serratia marcescens (n = 44),
      and Pseudomonas aeruginosa (n = 114). The minimum inhibitory concentrations of 39
      antibacterial agents used for these strains were determined according to the
      Clinical and Laboratory Standards Institute (CLSI) manual. All Enterococcus
      faecalis strains were susceptible to ampicillin and vancomycin. Although a
      majority of the E. faecalis strains were susceptible to linezolid, 11 strains
      (7.8%) were found to be intermediately resistant. The proportions of
      fluoroquinolone-resistant Enterococcus faecalis, Escherichia coli, Proteus
      mirabilis, and S. marcescens strains were 35.7%, 29.3%, 18.3%, and 15.2%,
      respectively. The proportions of E. coli, P. mirabilis, K. pneumoniae, and S.
      marcescens strains producing extended-spectrum beta-lactamase were 5.1%, 11.9%,
      0%, and 0%, respectively. The proportions of Pseudomonas aeruginosa strains
      resistant to carbapenems, aminoglycosides, and fluoroquinolones were 9.2%, 4.4%,
      and 34.8%, respectively, and among them, 2 strains (1.8%) were found to be
      multidrug resistant. These data present important information for the proper
      treatment of urinary tract infections and will serve as a useful reference for
      periodic surveillance studies in the future.

PMID- 21174143
TI  - Pulmonary hypertension confirmed histologically five months prior to scleroderma
      renal crisis onset.
AB  - A 69-year-old man presented shortness of breath and acute renal failure. He had
      undergone pulmonary partial resection for lung cancer 5 months prior. On
      examination, severe hypertension, skin sclerosis of his forearms, and
      anticentromere antibody were observed. A renal biopsy specimen showed
      characteristic findings for scleroderma renal crisis, and a right heart
      catheterization revealed severe pulmonary arterial hypertension. Re-examination
      of the resected lung specimen revealed sclerodermatous vascular involvement was
      present.

PMID- 21174144
TI  - H5N1 influenza vaccine formulated with AS03 A induces strong cross-reactive and
      polyfunctional CD4 T-cell responses.
AB  - OBJECTIVE: Adjuvantation of an H5N1 split-virion influenza vaccine with AS03(A)
      substantially reduces the antigen dose required to produce a putatively
      protective humoral response and promotes cross-clade neutralizing responses. We
      determined the effect of adjuvantation on antibody persistence and B- and T-cell
      mediated immune responses. METHODS: Two vaccinations with a split-virion
      A/Vietnam/1194/2004 (H5N1, clade 1) vaccine containing 3.75-30 MUg hemagglutinin
      and formulated with or without adjuvant were administered to groups of 50
      volunteers aged 18-60 years. RESULTS: Adjuvantation of the vaccine led to better
      persistence of neutralizing and hemagglutination-inhibiting antibodies and higher
      frequencies of antigen-specific memory B cells. Cross-reactive and polyfunctional
      H5N1-specific CD4 T cells were detected at baseline and were amplified by
      vaccination. Expansion of CD4 T cells was enhanced by adjuvantation. CONCLUSION:
      Formulation of the H5N1 vaccine with AS03(A) enhances antibody persistence and
      induces stronger T- and B-cell responses. The cross-clade T-cell immunity
      indicates that the adjuvanted vaccine primes individuals to respond to either
      infection and/or subsequent vaccination with strains drifted from the primary
      vaccine strain.

PMID- 21174146
TI  - Participation, power, and the role of community psychology in environmental
      disputes: a tale of two nuclear cities.
AB  - This paper examines public participation and the role of community psychology in
      an emerging environmental dispute relevant to global climate change (GCC)-whether
      nuclear power represents a "green" solution. From a dialectical position, we
      explore the nuclear debate as it is linked to GCC, and more specifically, how
      participation in related federally-mandated processes may be shaped by power. We
      present qualitative data from public meetings in two nuclear communities and
      analyze these data through a lens of social power and environmental justice,
      including an examination of nukespeak and telepolitical appeals to highlight the
      complexity of the issues, how the appearance of successful participation may be
      deceptive, and how consensus may be manipulated. We argue that CP should consider
      GCC to be one of the most significant social problems of our time and make every
      effort to be involved in the search for truly "green" solutions.

PMID- 21174145
TI  - Achievement of lipid targets with the combination of rosuvastatin and fenofibric
      Acid in patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: The objective of this study was to assess the proportion of patients
      with type 2 diabetes mellitus (T2DM) attaining individual and combined targets of
      low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol
      (HDL-C), triglycerides (TG), non-HDL-C, and apolipoprotein B (ApoB) after
      treatment with rosuvastatin (R) + fenofibric acid (FA) compared with
      corresponding-dose R monotherapy. METHODS: This post hoc analysis evaluated data
      from the T2DM subset of patients with mixed dyslipidemia (LDL-C >=130 mg/dL, HDL
      C <40/50 mg/dL in men/women, and TG >=150 mg/dL) from 2 randomized studies.
      Patients included in the analysis (N = 456) were treated with R (5, 10, or 20
      mg), FA 135 mg, or R (5, 10, or 20 mg) + FA 135 mg for 12 weeks. Attainment of
      LDL-C <100 mg/dL, HDL-C >40/50 mg/dL in men/women, TG <150 mg/dL, non-HDL-C <130
      mg/dL, ApoB <90 mg/dL, and the combined targets of these parameters was assessed.
      RESULTS: Treatment with R + FA resulted in a significantly higher proportion of
      patients achieving optimal levels of HDL-C (46.8% vs. 20.8%, P = 0.009 for R 10
      mg + FA), TG (60.0% vs. 34.0%, P = 0.02 for R 10 mg + FA; 54.0% vs. 26.4%, P =
      0.005 for R 20 mg + FA), non-HDL-C (55.1% vs. 36.4%, P = 0.04 for R 5 mg + FA),
      ApoB (58.0% vs. 36.4%, P = 0.02 for R 5 mg + FA); and the combined targets of LDL
      C, HDL-C, and TG (28.3% vs. 8.3%, P = 0.02 for R 10 mg + FA) and all 5 parameters
      (26.1% vs. 8.3%, P = 0.03 for R 10 mg + FA) than corresponding-dose R
      monotherapies. CONCLUSIONS: A significantly greater proportion of T2DM patients
      achieved individual and combined lipid targets when treated with the combination
      of R + FA than corresponding-dose R monotherapies.

PMID- 21174147
TI  - Excretion into feces of asialo GM1 in the murine digestive tract and
      Lactobacillus johnsonii exhibiting binding ability toward asialo GM1. A possible
      role of epithelial glycolipids in the discharge of intestinal bacteria.
AB  - In the digestive tract of mice (HR-1, 5 months old, ?), asialo GM1 (GA1)
      exhibiting receptor activity toward several intestinal bacteria was
      preferentially expressed in the small intestine. Also, less than 10% of GA1 in
      the small intestine was converted into fucosylated and sulfated derivatives, but
      it was completely converted to fucosyl GA1 (FGA1) in the stomach, cecum and
      colon. Among the lipid components in these tissues, glycolipids other than
      Forssman antigen and cholesterol sulfate (CS) were present in the digestive tract
      contents. However, sulfated GA1, sulfatide and fucosyl GM1 in the gastro
      intestinal contents were not present in the cecal and colonic contents, in which
      the major glycolipids were ceramide monohexoside (CMH), GA1 and FGA1. The total
      amount of GA1 in the whole contents was 20% of that in the tissues. Thus,
      glycolipids were stable during the process of digestion, and excreted from the
      body together with cholesterol and CS. On the other hand, Lactobacillus johnsonii
      (LJ), whose receptor is GA1, was detected in the cecal and colonic contents on
      sequential analysis of 16S-ribosomal RNA and TLC-immunostaining of antigenic
      glycolipids with anti-LJ antiserum. LJ was found to comprise 20% of the total
      bacteria cultured in the lactobacillus medium under aerobic conditions, and to be
      present in the cecal and colonic contents, 9.8 * 10(7) cells versus 37 MUg GA1
      and 1.4 * 10(8) cells versus 49 MUg GA1, respectively. Thus, GA1 in the contents
      might facilitate the discharge of intestinal bacteria by becoming attached them
      to prevent their irregular diffusion.

PMID- 21174148
TI  - Annual variations of the plasmatic levels of glucose and amino acid and daily
      changes under different natural conditions of temperature and photoperiod in
      Gilthead Sea bream (Sparus aurata, L.).
AB  - Daily and annual changes in the plasmatic glucose and amino acid concentration
      have been determined in Sparus aurata L. Fish (average weight 330 g) were kept in
      cages under natural conditions of temperature and photoperiod and fed with a
      commercial diet. The months studied were chosen to establish whether there is any
      influence on the plasmatic glucose and amino acid concentration due to the change
      in temperature and photoperiod (equal photoperiod and different temperature,
      March and October; different photoperiod and equal temperature, May and November;
      and different photoperiod and temperature, June and January). To study the daily
      profile of glucose and amino acids concentrations, blood was extracted from six
      fish every 3 h during 24 h. Annual changes were determined as the average of the
      samples obtained during 1 day. Results show an annual rhythm with acrophase in
      June with a positive correlation with photoperiod for glucose and amino acids and
      with temperature only for amino acids. Daily profiles are rhythmical with a
      period of 24 h except in November with a period of 8 h for amino acids.

PMID- 21174149
TI  - Relapse of intestinal and hepatic amebiasis after treatment.

PMID- 21174151
TI  - Comparison of plaque prolapse in consecutive patients treated with Xience V and
      Taxus Liberte stents.
AB  - The purpose of this article is to investigate the prevalence of plaque prolapse
      (PP) after Xience V and Taxus Liberte stent implantation. During the study period
      2006-2007, 200 consecutive patients underwent coronary revascularization for de
      novo lesions and received an intravascular ultrasound (IVUS) post-stenting
      evaluation, (n = 124 patients with Taxus Liberte and n = 76 with Xience V) (227
      stent segments). Cross-sectional and longitudinal 3D IVUS images were analyzed in
      a blind fashion, evaluating the prevalence of PP and calculating its depth and
      angle. The angulation degree of the coronary artery at the lesion site pre-stent
      implantation was also evaluated by angiography. The prevalence of PP was 23.9% in
      Xience V versus 38.1% in Taxus Liberte (P = 0.025). The depth and angle of PP
      were greater in Taxus Liberte stent than Xience V stent (0.4 +/- 0.1 mm versus
      0.5 +/- 0.2 mm, P = 0.004; and 32.0 +/- 8.9 degrees  versus 44.6 +/- 27.6 degrees
      , P = 0.044, respectively). The angulation degree of the coronary artery at the
      lesion site was higher in presence of plaque prolapse than in its absence (48.2
      +/- 29.3 degrees  vs. 38.2 +/- 28.1 degrees , P = 0.013). By multivariate
      analysis, stent type was independently associated with incidence of plaque
      prolapse. Xience V stent has less plaque prolapse than Taxus Liberte stent. Stent
      design may play a role in the prevalence of plaque prolapse.

PMID- 21174150
TI  - Development of FRET assay into quantitative and high-throughput screening
      technology platforms for protein-protein interactions.
AB  - Forster resonance energy transfer (FRET) technology has been widely used in
      biological and biomedical research and is a very powerful tool in elucidating
      protein interactions in many cellular processes. Ubiquitination and SUMOylation
      are multi-step cascade reactions, involving multiple enzymes and protein-protein
      interactions. Here we report the development of dissociation constant (K (d))
      determination for protein-protein interaction and cell-based high-throughput
      screening (HTS) assay in SUMOylation cascade using FRET technology. These
      developments are based on steady state and high efficiency of fluorescent energy
      transfer between CyPet and YPet fused with SUMO1 and Ubc9, respectively. The
      developments in theoretical and experimental procedures for protein interaction K
      (d) determination and cell-based HTS provide novel tools in affinity measurement
      and protein interaction inhibitor screening. The K (d) determined by FRET between
      SUMO1 and Ubc9 is compatible with those determined with other traditional
      approaches, such as isothermal titration calorimetry (ITC) and surface plasmon
      resonance (SPR). The FRET-based HTS is pioneer in cell-based HTS. Both K (d)
      determination and cell-based HTS, carried out in 384-well plate format, provide
      powerful tools for large-scale and high-throughput applications.

PMID- 21174152
TI  - Primary tumor volume is an independent predictor of outcome within pT4a-staged
      tongue carcinoma.
AB  - BACKGROUND: We evaluated the heterogeneity of primary tumor volume (PTV) within
      tumors of the same pT4a-staged tongue carcinoma and to elucidate the effects of
      PTV on treatment outcomes in patients with pT4a-staged tongue carcinoma. METHODS:
      Fifty-eight patients with newly diagnosed pT4a-staged tongue carcinoma who
      received surgery were enrolled onto this study. Magnetic resonance imaging
      derived PTV was measured by the summation-of-area technique. RESULTS: The mean
      PTV was 24.55 ml, with a range of 5.32 to 119.64 ml. The receiver operating
      characteristic curve was applied, and the optimal cutoff volume was 23 ml. Large
      PTV was associated with a significantly poor disease-specific survival (P =
      0.010) by the log rank test. The Cox regression model also revealed that large
      PTV (P = 0.026) and positive lymphatic node metastasis (P = 0.004) were
      statistically significant in the prognosis of T4a-staged tongue carcinoma.
      CONCLUSIONS: A substantial variation of PTV was present within the same pT4a
      staged tongue carcinoma, and PTV represented an important prognostic factor. In
      the light of these findings, we suggest that taking the PTV into account in pT4a
      staged tongue carcinoma would better refine the newest revised T classification,
      and the treatment strategies may be different.

PMID- 21174155
TI  - Nipple-sparing mastectomy in 99 patients with a mean follow-up of 5 years.
AB  - BACKGROUND: The safety and practicality of nipple-sparing mastectomy (NSM) are
      controversial. METHODS: Review of a large breast center's experience identified
      99 women who underwent intended NSM with subareolar biopsy and breast
      reconstruction for primary breast cancer. Outcome was assessed by biopsy status,
      postoperative nipple necrosis or removal, cancer recurrence, and cancer-specific
      death. RESULTS: NSM was attempted for invasive cancer (64 breasts, 24 with
      positive lymph nodes), noninvasive cancer (35 breasts), and/or contralateral
      prophylaxis (50 breasts). Twenty-two nipples (14%) were removed because of
      positive subareolar biopsy results (frozen or permanent section). Seven patients
      underwent a pre-NSM surgical delay procedure because of increased risk for nipple
      necrosis. Reconstruction used transverse rectus abdominis myocutaneous flaps (56
      breasts), latissimus flaps with expander (35 breasts), or expander alone (58
      breasts). Of 127 retained nipples, 8 (6%) became necrotic and 2 others (2%) were
      removed at patient request. There was no nipple necrosis when NSM was performed
      after a surgical delay procedure. At a mean follow-up of 60.2 months, all 3
      patients with recurrence had biopsy-proven subareolar disease and had undergone
      nipple removal at original mastectomy. There were no deaths. CONCLUSIONS: Five
      year recurrence rate is low when NSM margins (frozen section and permanent) are
      negative. Nipple necrosis can be minimized by incisions that maximize perfusion
      of surrounding skin and by avoiding long flaps. A premastectomy surgical delay
      procedure improves nipple survival in high-risk patients. NSM can be performed
      safely with all types of breast reconstruction.

PMID- 21174156
TI  - Expanding the indications for latissimus dorsi musculocutaneous flap in totally
      autologous breast reconstruction: the extended variant.

PMID- 21174157
TI  - Combined thermal-surgical ablation of locally advanced abdominopelvic
      malignancies.
AB  - BACKGROUND: Treatment options for patients with inoperable primary or
      recurrent/metastatic abdominopelvic malignancies are limited, and these patients
      have short lifespan. The purpose of our study is to examine outcomes of combined
      open radiofrequency ablation (RFA) and surgical debulking of otherwise
      unresectable tumors. METHODS: Consecutive 50 patients were identified from an
      Institutional Review Board (IRB)-approved database undergoing ablation for
      unresectable abdominopelvic malignancies via conventional surgical methods in a
      single institution between 07/2003 and 09/2009. Patients were selected for
      debulking if they had a dominant mass that caused significant symptoms. RESULTS:
      Sixteen patients had primary tumors, and 34 presented with a recurrent/metastatic
      malignancy. The primary tumors were abdominopelvic sarcomas (eight patients),
      large desmoids (two), colorectal cancer (CRC) (two), and gastric cancer, mucinous
      cystic pancreatic neoplasm, gastrointestinal stromal tumor (GIST), and carcinoid
      (one each). The recurrent/metastatic tumors were CRCs (16 patients),
      abdominopelvic sarcomas (12), and GIST, prostate cancer, bladder cancer,
      melanoma, adrenal cancer, and pseudomyxoma peritonei recurrences (1 each). Twenty
      two patients were alive and 28 died as of September 2009. Median survival for
      patients who died was 9.5 months and for patients who were alive was 22 months.
      Patients with primary tumors had 5-year survival of 18% compared with no
      survivors at 5 years in the recurrent/metastatic group (P = 0.002). CONCLUSIONS:
      Thermosurgical ablation of otherwise unresectable primary tumors and
      recurrent/metastatic abdominopelvic malignancies is feasible in selected cases.
      Patients with ablated primary tumors have a survival advantage over patients who
      have ablation for recurrent/metastatic disease.

PMID- 21174158
TI  - Elastic light-scattering spectroscopy for discrimination of benign from malignant
      disease in thyroid nodules.
AB  - BACKGROUND: Thyroid cancer is the most common endocrine malignancy. The current
      standard of diagnosis, fine-needle aspiration biopsy, yields approximately 10-25%
      of indeterminate results leading to twice as many thyroidectomies for further
      diagnosis. Elastic scattering spectroscopy (ESS) is a new, minimally invasive
      optical-biopsy technique mediated by fiber-optic probes that is sensitive to
      cellular and subcellular morphological features. We assessed the diagnostic
      potential of ESS in the thyroid to differentiate benign from malignant thyroid
      nodules as determined by histology. METHODS: Under an IRB approved protocol, 36
      surgical patients (n = 21 benign thyroid nodules, n = 15 malignant tumors) had
      collection of ESS data from their fresh ex vivo thyroidectomy specimens. Using
      surgical pathology as our gold standard, spectral analyses were performed using a
      training set; these data were used to assess the ESS diagnostic potential using
      the leave-one-out technique. RESULTS: Our test set was 75% sensitive and 95%
      specific in differentiating benign from malignant thyroid lesions, with a
      positive predictive value (PPV) of 0.92 and a negative predictive value (NPV) of
      0.83. CONCLUSIONS: The ESS can accurately distinguish benign vs malignant thyroid
      lesions with high PPV and NPV. With further validation ESS could potentially be
      used as an in situ real-time diagnostic tool or as an adjunct to conventional
      cytology.

PMID- 21174159
TI  - Shifting incidence of solitary adenomas in the era of minimally invasive
      parathyroidectomy. A multi-institutional study.
AB  - BACKGROUND: Previously, when a conventional neck exploration (CNE) without
      preceding diagnostic imaging was the surgical treatment for patients with primary
      hyperparathyroidism (pHPT) solitary adenomas were observed in 69-88% of patients.
      The advent of minimally invasive parathyroidectomy (MIP), aiming at a
      preoperatively identified parathyroid abnormality may be associated with a
      different incidence of solitary and multiglandular parathyroid disease. MATERIALS
      AND METHODS: In a cohort of 467 patients with sporadic pHPT who preferentially
      underwent MIP in four hospitals in the same geographical region, the incidence of
      solitary adenomas, multiple adenomas, and multiglandular hyperplasia (MGD) was
      evaluated. RESULTS: A total of 367 patients were scheduled for MIP; 100 patients
      underwent a planned CNE. The overall surgical success rate of the first operation
      was 93%, and the cumulative success rate, including a second operative procedure,
      was 99%. Normocalcemia resulted from removing 1 abnormal PG in 426 patients (91%)
      and more than one abnormal gland in 35 patients (8%). A parathyroid carcinoma was
      diagnosed in four of the 426 patients with a single abnormal gland. Four gland
      hyperplasia was observed in 1 patient. In hospitals where diagnostic workup
      usually consisted of ultrasound (US) and computed tomography (CT) the incidence
      of solitary adenomas was 88%, compared with 96% in hospitals where MIBI, US, and
      CT were used preoperatively (P = 0.007). CONCLUSIONS: A higher frequency of
      solitary adenomas was observed than historically reported. The extent of the
      preoperative workup influences the number of observed solitary adenomas.

PMID- 21174160
TI  - A mechatronic valve in the management of hydrocephalus: methods and performance.
AB  - The problem of excess cerebrospinal fluid in the brain (hydrocephalus) is
      generally managed using a passive pressure or flow regulated mechanical shunt.
      Despite the success of such devices, they have been plagued with a number of
      problems. It is desirable to have a shunt valve that responds dynamically to the
      changing needs of the patient, opening and closing according to a dynamic
      physiological pattern, rather than simply to the hydrostatic pressure across the
      valve. Such a valve would by necessity be mechatronic, electronically controlled
      by software. In this article, different methods for controlling such a
      mechatronic valve are explored, and the effect of current hydrocephalus
      management techniques on the intracranial hydrodynamics of acute hydrocephalus
      patient compared with those based on a mechatronic valve was investigated using
      numerical simulation. Furthermore, the performance of these techniques was
      evaluated based on a proposed multi-dimensional figure of merit. In addition, an
      empirical valve schedule was proposed based on different criterions. An
      intelligent shunting system is seen as the future in hydrocephalus management and
      treatment, and towards this end, suitably programmed mechatronic valves would
      attempt to mimic normal physiology and potentially overcome many of the problems
      associated with current mechanical valves.

PMID- 21174162
TI  - Transitions in care.

PMID- 21174163
TI  - Visit to the radiologist.

PMID- 21174161
TI  - Do ongoing lifestyle disruptions differ across cancer types after the conclusion
      of cancer treatment?
AB  - INTRODUCTION: Cancer interferes with participation in valued lifestyle activities
      (illness intrusiveness) throughout post-treatment survivorship. We investigated
      whether illness intrusiveness differs across life domains among survivors with
      diverse cancers. Intrusiveness should be highest in activities requiring
      physical/cognitive functioning (instrumental domain). Intrusiveness into
      relationship/sexual functioning (intimacy domain) should be higher in prostate,
      breast, and gastrointestinal cancers than in others. METHODS: Cancer outpatients
      (N = 656; 51% men) completed the Illness Intrusiveness Ratings Scale (IIRS)
      during follow-up. We compared IIRS Instrumental, Intimacy, and Relationships and
      Personal Development [RPD] subscale and total scores across gastrointestinal,
      lung, lymphoma, head and neck, prostate (men), and breast cancers (women),
      comparing men and women separately. RESULTS: Instrumental subscale scores (M(men)
      = 3.05-3.80, M(women) = 3.02-3.63) were highest for all groups, except prostate
      cancer. Men with prostate cancer scored higher on Intimacy (M = 3.40) than
      Instrumental (M = 2.48) or RPD (M = 1.59), p's < .05; their Intimacy scores did
      not differ from men with gastrointestinal or lung cancer. Women collectively
      showed higher Instrumental (M = 3.39) than Intimacy (M = 2.49) or RPD scores (M =
      2.27), p's < .001, but not the hypothesized group difference in Intimacy.
      CONCLUSIONS: Post-treatment survivors continue to experience some long-term
      interference with activities requiring physical and cognitive functioning. Sexual
      adjustment may be of special concern to men when treatments involve genitourinary
      functioning. IMPLICATIONS FOR CANCER SURVIVORS: Ongoing monitoring with the IIRS
      to detect lifestyle interference throughout survivorship may enhance quality of
      life. Screening and intervention should target particular life domains rather
      than global interference.

PMID- 21174164
TI  - Could media reports include a standardized scale for quality of evidence?
AB  - While some media reports offer accurate interpretations of clinical research,
      other reports are misleading. The uneven accuracy of medical reporting may act in
      concert with its sheer volume to confuse the lay public about which health
      messages are most important and evidence-based. I outline one possible step
      towards a solution: medical journals can embed quality of evidence ratings in
      article summaries and create incentives for inclusion of these ratings in lay
      media reports.

PMID- 21174165
TI  - Primary language, income and the intensification of anti-glycemic medications in
      managed care: the (TRIAD) study.
AB  - BACKGROUND: Patients who speak Spanish and/or have low socioeconomic status are
      at greater risk of suboptimal glycemic control. Inadequate intensification of
      anti-glycemic medications may partially explain this disparity. OBJECTIVE: To
      examine the associations between primary language, income, and medication
      intensification. DESIGN: Cohort study with 18-month follow-up. PARTICIPANTS: One
      thousand nine hundred and thirty-nine patients with Type 2 diabetes who were not
      using insulin enrolled in the Translating Research into Action for Diabetes Study
      (TRIAD), a study of diabetes care in managed care. MEASUREMENTS: Using
      administrative pharmacy data, we compared the odds of medication intensification
      for patients with baseline A1c >= 8%, by primary language and annual income.
      Covariates included age, sex, race/ethnicity, education, Charlson score, diabetes
      duration, baseline A1c, type of diabetes treatment, and health plan. RESULTS:
      Overall, 42.4% of patients were taking intensified regimens at the time of follow
      up. We found no difference in the odds of intensification for English speakers
      versus Spanish speakers. However, compared to patients with incomes <$15,000,
      patients with incomes of $15,000-$39,999 (OR 1.43, 1.07-1.92), $40,000-$74,999
      (OR 1.62, 1.16-2.26) or >$75,000 (OR 2.22, 1.53-3.24) had increased odds of
      intensification. This latter pattern did not differ statistically by race.
      CONCLUSIONS: Low-income patients were less likely to receive medication
      intensification compared to higher-income patients, but primary language (Spanish
      vs. English) was not associated with differences in intensification in a managed
      care setting. Future studies are needed to explain the reduced rate of
      intensification among low income patients in managed care.

PMID- 21174167
TI  - Chronic pain practice by consultant anaesthetists in the Republic of Ireland.
AB  - BACKGROUND: To date, there is no information on anaesthetists' practice of
      chronic pain management in the Republic of Ireland. AIMS: To describe the pattern
      of chronic pain practice (CPP) among consultant anaesthetists in Ireland.
      METHODS: A detailed questionnaire was sent to all consultant anaesthetists in the
      Republic of Ireland (n = 254). RESULTS: The overall response rate was 50% (n =
      127). While 28% of responding anaesthetists were involved in CPP, in the majority
      of cases, this accounted for less than 20% of their clinical time. 39% of those
      involved in CPP had previous training in chronic pain management. The types of
      CPP included nerve blocks (67%) and pharmacological treatment (44%) in non-cancer
      pain (67%) and cancer pain (61%) patients. Epidural steroid injection was the
      most commonly practiced intervention (89%). CONCLUSION: One-third of consultant
      anaesthetists in the Republic surveyed incorporate chronic pain in their practice
      and their pattern of practice is widely diversified.

PMID- 21174166
TI  - Diet, obesity and cancer.
AB  - INTRODUCTION AND AIMS: Obesity and the rising incidence of certain cancers are
      the manifest expressions of problems with diet and lifestyle. A number of complex
      and closely inter-related factors mediate the association between environment and
      cancer development. This review seeks to summarise the current evidence
      pertaining to dietary factors and cancer incidence and progression. METHODS:
      Relevant literature was identified by search of the Pubmed database using the
      terms: diet, cancer, carcinogenesis, tumourigenesis. References from relevant
      articles were searched. Selection of articles was based on peer review, journal
      and relevance. Where possible, meta-analyses of randomised controlled trials
      (RCTs) or large RCTs were cited preferentially. RESULTS: Variations in cancer
      trends between geographic regions and in migration studies point to the key role
      of environmental differences in cancer incidence. Mechanisms of tumorigenesis,
      including inflammation, angiogenesis, may be influenced by specific dietary
      constituents including glucosinolates, organosulphur compounds, genistein,
      curcumin, catechins, resveratrol and lycopene. CONCLUSION: Despite
      epidemiological evidence suggesting a link between dietary factors and cancer
      development, confounding factors such as obesity, physical activity and the sheer
      variety of bioactive compounds in a normal diet pose a great challenge to the
      study of mechanisms linking diet and cancer. A greater understanding of the
      interplay between dietary constituents and cancer development should un-cover new
      targets for the prevention and treatment of cancer.

PMID- 21174168
TI  - Changes of iron stores and duodenal transepithelial iron transfer during regular
      exercise in rats.
AB  - It is unclear whether regular exercise depletes body iron stores and how exercise
      regulates iron absorption. In this study, growing female Sprague-Dawley rats were
      fed a high-iron diet (300 mg iron/kg) and subjected to swimming for 1, 3, or 12
      months. Their body weight, liver nonheme iron content (NHI), spleen NHI, blood
      hemoglobin (Hb) concentration, hematocrit (Hct), and kinetics of 59Fe transfer
      across isolated duodenal segments were then compared with sedentary controls. The
      main results were as follows: exercise for 1 month enhanced the transepithelial
      59Fe transfer and increased liver NHI content and Hb concentration; exercise for
      3 months inhibited transepithelial 59Fe transfer without affecting the liver and
      spleen NHI content, Hb concentration, and Hct; exercise for 12 months did not
      affect these parameters as compared with the corresponding sedentary controls;
      and the changes in transepithelial iron transfer were not associated with
      basolateral iron transfer. Our findings demonstrated that chronic, regular
      exercise in growing rats with a high dietary iron content does not deplete iron
      stores in the liver and spleen and may possibly enhance or inhibit duodenal iron
      absorption and even maintain duodenal iron absorption at the sedentary level, at
      least, in part depending on growth.

PMID- 21174169
TI  - Near-infrared chemometric approach to exhaustive analysis of rice straw
      pretreated for bioethanol conversion.
AB  - We report a simple analytical procedure combining near-infrared (NIR)
      spectroscopy with multivariate analysis to detect the saccharification efficiency
      of pretreated rice straw. Three types of sample preparation methods were tested
      to develop a powerful calibration model, with the disk sample used as the
      standard protocol. From the spectra dataset of NaOH-treated biomass, we obtained
      a good calibration for the saccharification ratio and some major structural
      components by partial least-squares regression. Adding dataset from hot water and
      dilute sulfuric acid pretreatments to NaOH sample dataset, an acceptable
      calibration model to predict the saccharification ratio as well as the glucose,
      xylose, and lignin contents was generated. NIR has a great potential for rapid
      screening of saccharification efficiency of pretreated biomass, which would
      allows us to control the quality of processing toward better bioethanol
      production.

PMID- 21174170
TI  - Post-stroke infection: a role for IL-1ra?
AB  - BACKGROUND: Infection is common following stroke and is independently associated
      with worse outcome. Clinical studies suggest that infections occur more
      frequently in those individuals with stroke-induced immunologic dysfunction. This
      study sought to explore the contribution of immunomodulatory cytokines and
      hormones to lymphocyte function and infection risk. METHODS: Patients (N = 112)
      were enrolled as soon as possible after the onset of ischemic stroke. Blood was
      drawn to assess plasma cortisol, IL-10, IL-1ra, lymphocyte numbers, and
      lymphocyte function at 72 h after stroke onset; infections were censored through
      21 days after stroke onset. RESULTS: Infection occurred in 25% of patients.
      Stroke severity was the most important predictor of infection risk. Increased
      plasma cortisol, IL-10, and IL-1ra, as well as decreased lymphocyte numbers, at
      72 h after stroke onset were associated with risk of subsequent infection. After
      controlling for stroke severity, only IL-1ra was independently associated with
      infection risk, and the degree of risk was consistent throughout the post-stroke
      period. Infection, but not IL-1ra itself, was associated with worse outcome at 3
      months. CONCLUSIONS: In this study cohort, increased plasma IL-1ra was
      independently associated with the risk of post-stroke infection. Further studies
      are needed to validate this finding, which could have important implications for
      stroke therapy.

PMID- 21174173
TI  - Manganese encephalopathy: an under-recognized condition in the intensive care
      unit.
AB  - BACKGROUND: Manganese encephalopathy is a potential complication of parenteral
      nutrition. Lack of early recognition leads to unnecessary testing and to
      continued exposure to manganese. METHODS: Case report and review of the
      literature. RESULTS: We describe the clinical and imaging findings of a patient
      with manganese encephalopathy in whom the diagnosis was delayed due to lack of
      recognition of the characteristic imaging findings. CONCLUSION: Manganese
      encephalopathy has protean clinical and imaging findings that can easily be
      overlooked.

PMID- 21174171
TI  - Acute ischemic injury on diffusion-weighted magnetic resonance imaging after poor
      grade subarachnoid hemorrhage.
AB  - BACKGROUND: Poor clinical condition is the most important predictor of
      neurological outcome and mortality after subarachnoid hemorrhage (SAH). Rupture
      of an intracranial aneurysm was shown to be associated with acute ischemic brain
      injury in poor grade patients in autopsy studies and small magnetic resonance
      imaging series. METHODS: We performed diffusion-weighted magnetic resonance
      imaging (DWI) within 96 h of onset in 21 SAH patients with Hunt-Hess grade 4 or 5
      enrolled in the Columbia University SAH Outcomes Project between July 2004 and
      February 2007. We analyzed demographic, radiological, clinical data, and 3 months
      outcome. RESULTS: Of the 21 patients 13 were Hunt-Hess grade 5, and eight were
      grade 4. Eighteen patients (86%) displayed bilateral and symmetric abnormalities
      on DWI, but not on computed tomography (CT). Involved regions included both
      anterior cerebral artery territories (16 patients), and less often the thalamus
      and basal ganglia (4 patients), middle (6 patients) or posterior cerebral artery
      territories (2 patients), or cerebellum (2 patients). At 1-year, 15 patients were
      dead (life support had been withdrawn in 6), 2 were moderately to severely
      disabled (modified Rankin Scale [mRS] = 4-5), and 4 had moderate-to-no disability
      (mRS = 1-3). CONCLUSIONS: Admission DWI demonstrates multifocal areas of acute
      ischemic injury in poor grade SAH patients. These ischemic lesions may be related
      to transient intracranial circulatory arrest, acute vasoconstriction,
      microcirculatory disturbances, or decreased cerebral perfusion from neurogenic
      cardiac dysfunction. Ischemic brain injury in poor grade SAH may be a feasible
      target for acute resuscitation strategies.

PMID- 21174172
TI  - Post-operative dexmedetomidine-based sedation after uneventful intracranial
      surgery for unruptured cerebral aneurysm: comparison with propofol-based
      sedation.
AB  - BACKGROUND: Clinical applications of dexmedetomidine (DEX) for neurosurgical
      procedures have not been adequately investigated. This study aimed to test the
      use of DEX infusion, alone or as an adjunct to propofol infusion, as compared to
      propofol infusion in patients with an unruptured cerebral aneurysm after
      uneventful intracranial procedures. METHODS: In this retrospective observational
      study from a single institute, of 184 patients who underwent uneventful
      intracranial procedures for an unruptured cerebral aneurysm between January 2003
      and March 2007, we reviewed 50 managed with DEX-based sedation (DEX alone or as
      an adjunct to propofol infusion) between April 2005 and March 2007, and 50
      managed with propofol-based sedation (propofol alone) between January 2003 and
      April 2005. With DEX-based sedation, both intubated and extubated patients
      received DEX infusion at an initial dose of 0.4 MUg/kg/h, followed by a
      maintenance dose of 0.2-0.7 MUg/kg/h. Propofol was used in both groups at a dose
      range of 0.5-5.0 mg/kg/h. Hemodynamic variables, including heart rate (HR) and
      blood pressure (BP), and adverse events were recorded and compared between the
      groups. RESULTS: HR during sedation and systolic BP at 2 h after beginning
      sedation were significantly lower in the DEX group. No serious adverse events
      were observed. In the DEX group, 66% were sedated in combination with propofol,
      of whom 94% were intubated. CONCLUSIONS: DEX could be used safely for both
      intubated and extubated patients following uneventful intracranial procedures for
      an unruptured cerebral aneurysm, though it significantly reduced HR. Our findings
      also indicate that it is preferable to add low-dose propofol to DEX for
      management of intubated patients.

PMID- 21174174
TI  - Solitary subcutaneous metastasis from squamous cell carcinoma of the esophagus: a
      case report and brief review of literature.

PMID- 21174176
TI  - Treatment of refractory status epilepticus in childhood.
AB  - Refractory status epilepticus (RSE) is characterized by a prolonged seizure that
      persists despite adequate initial management. RSE accounts for almost one quarter
      of all status epilepticus and carries significant risk for morbidity and
      mortality. Treatment varies widely between institutions regarding medication
      choice, dose, and monitoring. Several agents including nonanesthetic
      antiepileptic drugs (AEDs), anesthetic AEDs, enteral AEDs, and other therapies
      have been used in RSE. We review the current treatment strategies for RSE,
      focusing on patient selection, monitoring, optimal dosing and administration of
      medications, efficacy, adverse effects, and treatment duration.

PMID- 21174177
TI  - Positive correlations between tumor uptake on FDG PET and energy expenditure of
      patients with esophageal cancer.
AB  - PURPOSE: Cancer patients are prone to clinical malnutrition; moreover, the energy
      expenditure in patients with certain cancers is higher than that in healthy
      individuals, rendering their nutritional management a challenging issue. We
      hypothesized that 2-deoxy-2-[(18)F]fluoro-D: -glucose (FDG) uptake on positron
      emission tomography (PET) may be related to the energy expenditure and analyzed
      the FDG uptake and energy expenditure in esophageal cancer patients to clarify
      this. METHODS: Esophageal cancer patients [n = 13, 10 males and 3 females, age
      66.5 +/- 8.9 (51-82) years] were evaluated for FDG uptake using PET. The resting
      energy expenditure (REE) and basal energy expenditure (BEE) were calculated using
      indirect calorimetry and the Harris-Benedict formula, respectively. Regression
      analyses were performed to compare the parameters of imaging and energy
      expenditure. RESULTS: Positive correlations were found between tumor uptake on
      FDG PET and the parameters of energy expenditure. Among them, the correlations
      between SUV(max) and the ratio of REE to BEE (REE/BEE, r = 0.59; p = 0.035) and
      between SUV(max) and the difference between REE and BEE (REE - BEE, r = 0.58; p =
      0.036) were moderate and statistically significant. Further, the correlation
      between tumor uptake expressed as a percentage (%TU) and REE/BEE was mild (r =
      0.51) but not significant (p = 0.07), while that between %TU and REE-BEE was weak
      (r = 0.42) and not significant (p = 0.15). CONCLUSION: Significant positive
      correlations between SUV(max) on FDG PET and energy expenditure were noted in our
      study; we consider that these results may aid in determining the nutritional
      management for esophageal cancer patients.

PMID- 21174175
TI  - Can clues from evolution unlock the molecular development of the cerebellum?
AB  - The cerebellum sits at the rostral end of the vertebrate hindbrain and is
      responsible for sensory and motor integration. Owing to its relatively simple
      architecture, it is one of the most powerful model systems for studying brain
      evolution and development. Over the last decade, the combination of molecular
      fate mapping techniques in the mouse and experimental studies, both in vitro and
      in vivo, in mouse and chick have significantly advanced our understanding of
      cerebellar neurogenesis in space and time. In amniotes, the most numerous cell
      type in the cerebellum, and indeed the brain, is the cerebellar granule neurons,
      and these are born from a transient secondary proliferative zone, the external
      granule layer (EGL), where proliferation is driven by sonic hedgehog signalling
      and causes cerebellar foliation. Recent studies in zebrafish and sharks have
      shown that while the molecular mechanisms of neurogenesis appear conserved across
      vertebrates, the EGL as a site of shh-driven transit amplification is not, and is
      therefore implicated as a key amniote innovation that facilitated the evolution
      of the elaborate foliated cerebella found in birds and mammals. Ellucidating the
      molecular mechanisms underlying the origin of the EGL in evolution could have
      significant impacts on our understanding of the molecular details of cerebellar
      development.

PMID- 21174178
TI  - 18F-FDG uptake on PET helps predict outcome and response after treatment in
      unresectable thymic epithelial tumors.
AB  - BACKGROUND: Positron emission tomography (PET) with fluorine-18
      fluorodeoxyglucose ((18)F-FDG) has been studied in thymic epithelial tumors. We
      evaluated the usefulness of (18)F-FDG PET for monitoring after treatment in
      unresectable thymic epithelial tumors. METHOD: Twelve patients with
      unresectable/metastatic thymic epithelial tumors underwent PET study with (18)F
      FDG before and after chemotherapy or radiotherapy. Response and survival were
      analyzed according to the ratio of the peak standardized uptake value (SUV) of
      the tumor to the mean SUV of the mediastinum (T/M ratio). RESULTS: Partial
      response (PR) evaluated by Response Evaluation Criteria in Solid Tumors (RECIST)
      was noted in 4 (33%) of 12 patients, and partial metabolic response (PMR) was
      observed in 6 (50%) of 12 patients. PR was observed in 4 of 6 patients with PMR.
      In 6 patients with any response, the T/M ratio at post-treatment was
      significantly lower than at baseline (p = 0.0017). In 6 patients with stable
      disease (SD), stable metabolic disease (SMD) was observed in 5 by use of (18)F
      FDG PET. No statistically significant difference of (18)F-FDG uptake between at
      baseline and post-therapy was observed in 6 patients with SD (p = 0.4157) and SMD
      (p = 0.8419). Although the overall survival after treatment showed no
      statistically significant difference between PMR and SMD or progressive metabolic
      disease in the whole group of patients including thymoma, a statistically
      significant difference in the overall survival was observed between 5 patients
      with PMR and 5 patients with non-PMR (p = 0.0280). CONCLUSION: Our preliminary
      study suggests that (18)F-FDG PET is useful for monitoring response and outcome
      after treatment in unresectable thymic epithelial tumors.

PMID- 21174179
TI  - Guar gum, xanthan gum, and HPMC can define release mechanisms and sustain release
      of propranolol hydrochloride.
AB  - The objectives were to characterize propranolol hydrochloride-loaded matrix
      tablets using guar gum, xanthan gum, and hydroxypropylmethylcellulose (HPMC) as
      rate-retarding polymers. Tablets were prepared by wet granulation using these
      polymers alone and in combination, and physical properties of the granules and
      tablets were studied. Drug release was evaluated in simulated gastric and
      intestinal media. Rugged tablets with appropriate physical properties were
      obtained. Empirical and semi-empirical models were fit to release data to
      elucidate release mechanisms. Guar gum alone was unable to control drug release
      until a 1:3 drug/gum ratio, where the release pattern matched a Higuchi profile.
      Matrix tablets incorporating HPMC provided near zero-order release over 12 h and
      erosion was a contributing mechanism. Combinations of HPMC with guar or xanthan
      gum resulted in a Higuchi release profile, revealing the dominance of the high
      viscosity gel formed by HPMC. As the single rate-retarding polymer, xanthan gum
      retarded release over 24 h and the Higuchi model best fit the data. When mixed
      with guar gum, at 10% or 20% xanthan levels, xanthan gum was unable to control
      release. However, tablets containing 30% guar gum and 30% xanthan gum behaved as
      if xanthan gum was the sole rate-retarding gum and drug was released by Fickian
      diffusion. Release profiles from certain tablets match 12-h literature profiles
      and the 24-h profile of Inderal((r)) LA. The results confirm that guar gum,
      xanthan gum, and HPMC can be used for the successful preparation of sustained
      release oral propranolol hydrochoride tablets.

PMID- 21174180
TI  - Recent advances in lipid nanoparticle formulations with solid matrix for oral
      drug delivery.
AB  - Lipid nanoparticles based on solid matrix have emerged as potential drug carriers
      to improve gastrointestinal (GI) absorption and oral bioavailability of several
      drugs, especially lipophilic compounds. These formulations may also be used for
      sustained drug release. Solid lipid nanoparticle (SLN) and the newer generation
      lipid nanoparticle, nanostructured lipid carrier (NLC), have been studied for
      their capability as oral drug carriers. Biodegradable, biocompatible, and
      physiological lipids are generally used to prepare these nanoparticles. Hence,
      toxicity problems related with the polymeric nanoparticles can be minimized.
      Furthermore, stability of the formulations might increase than other liquid nano
      carriers due to the solid matrix of these lipid nanoparticles. These
      nanoparticles can be produced by different formulation techniques. Scaling up of
      the production process from lab scale to industrial scale can be easily achieved.
      Reasonably high drug encapsulation efficiency of the nanoparticles was
      documented. Oral absorption and bioavailability of several drugs were improved
      after oral administration of the drug-loaded SLNs or NLCs. In this review, pros
      and cons, different formulation and characterization techniques, drug
      incorporation models, GI absorption and oral bioavailability enhancement
      mechanisms, stability and storage condition of the formulations, and recent
      advances in oral delivery of the lipid nanoparticles based on solid matrix will
      be discussed.

PMID- 21174181
TI  - Aberrant cytoplasmic expression of cyclin B1 protein and its correlation with EBV
      LMP1, P53 and P16(INK4A) in classical Hodgkin lymphoma in China.
AB  - The relationships between the expression of cyclin B1, EBV-LMP1, P53 and
      P16(INK4A) in Chinese classical Hodgkin lymphoma are unknown and need exploring.
      Samples of classical Hodgkin lymphoma from 60 Chinese patients were analyzed for
      the expression of cyclin B1, EBV-LMP1, P53 and P16(INK4A) proteins by
      immunohistochemistry. Cyclin B1 protein was overexpressed in 90.0% (54/60) of
      this group of classical Hodgkin lymphoma, staining mainly and strongly in
      cytoplasm but also sparsely and weakly in nucleus of the Hodgkin and Reed
      Sternberg (HRS) cells. EBV-LMP1, P53 and P16(INK4A) were overexpressed in 85.0%,
      96.7% and 71.7% of Hodgkin lymphoma, respectively. EBV-LMP1, P53 and P16(INK4A)
      were was noted in the nucleus of HRS cells. Microscopically, cyclin B1 and P53
      staining distinguished the HRS cells from the complex background of lymphocytes.
      Cyclin B1 was positively correlated with EBV-LMP1(P < 0.001) and P53(P < 0.001),
      but was inversely related to P16(INK4A) (P < 0.05). It is suggested that
      overexpression of cyclin B1 could play an important role in the evolution of
      classical Hodgkin lymphoma, and cyclin B1 may be considered as a potential
      adjunct marker to identify HRS cells in diagnosis and be served as Hodgkin
      lymphoma-associated antigen in the near future.

PMID- 21174182
TI  - Multimodal analgesic approach incorporating paravertebral blocks for open radical
      retropubic prostatectomy: a randomized double-blind placebo-controlled study.
AB  - INTRODUCTION: Perioperative pain management influences both the quality as well
      as the speed of recovery following surgery. METHODS: This was a randomized double
      blind placebo-controlled study designed to assess the effectiveness of a
      multimodal analgesic approach (MMA) vs patient-controlled analgesia (PCA) alone
      in patients undergoing open prostatectomy. Prior to surgery, paravertebral blocks
      (PVBs) were performed with either 0.5% ropivacaine in the MMA group or saline in
      the PCA group. Patients in the MMA group also received celecoxib (400 mg po prior
      to surgery and 200 mg po bid for seven days following surgery) and ketamine 10 mg
      iv. Following surgery, every patient had free access to morphine PCA. A pain
      numerical rating scale (NRS) at 24 hr was chosen as the primary endpoint.
      Secondary endpoints included morphine consumption at 24 hr and SF-36 (36-Item
      Short-Form Health Survey) scores from two weeks to 24 weeks following surgery.
      RESULTS: The primary endpoint, average pain NRS at 24 hr, was 2.6 in the MMA
      group compared with 3.9 in the PCA group (difference = -1.6, 95% confidence
      interval [CI]: -2.3 to -0.4; P = 0.01). The average morphine consumption at 24 hr
      was 4.8 mg in the MMA group compared with 10.5 mg in the PCA group (difference = 
      5.7, 95% CI: -13.0 to 0.5; P = 0.01). Higher SF-36 scores at two, four, eight,
      and 12 weeks were observed in the MMA group compared with the PCA group, but no
      statistically significant (P < 0.05) between-group difference was found after
      Bonferroni correction of comparisons conducted repeatedly over time.
      Postoperative adverse effects included low episodes of postoperative nausea and
      vomiting, bladder spasms, constipation, and pruritus. CONCLUSION: This study
      demonstrates that PVBs combined with celecoxib and ketamine provide better
      immediate postoperative pain control and facilitate earlier functional recovery
      in patients undergoing an open radical prostatectomy when compared with PCA
      alone.

PMID- 21174183
TI  - Brief review: anesthetic neurotoxicity in the elderly, cognitive dysfunction and
      Alzheimer's disease.
AB  - PURPOSE: Postoperative cognitive decline in the elderly has emerged as a major
      health concern. In addition, there is a growing interest in the potential
      relationship between general anesthetic exposure and the onset and progression of
      Alzheimer's disease (AD). The available evidence of a possible association
      between anesthesia, surgery, and long-term cognitive effects, including AD,
      deserves consideration. In this review, we summarize the evidence for anesthesia
      induced neurotoxicity in the elderly, while highlighting the limitations of
      existing data, and we put the literature into perspective for the clinician.
      PRINCIPAL FINDINGS: A growing body of evidence suggests that general anesthetics
      may be neurotoxic to both young and aging brains. Much of the evidence originates
      from in vitro and in vivo studies with cells, rodents, and nonhuman primates.
      Despite the animal data suggesting a relationship between anesthesia and
      neurotoxicity in the elderly, a definitive link remains elusive in humans.
      CONCLUSIONS: The possible relation between anesthetic neurotoxicity,
      postoperative cognitive dysfunction, and AD remains elusive. It remains unclear
      whether postoperative cognitive decline in the elderly is related more to
      perioperative stress and related medical co-morbidities.

PMID- 21174185
TI  - Cardiotoxic overdose treated with intravenous fat emulsion and high-dose insulin
      in the setting of hypertrophic cardiomyopathy.
AB  - High-dose insulin (HDI) and intravenous fat emulsion (IFE) are used in overdoses,
      although rarely combined. To our knowledge, IFE therapy has not been reported in
      overdoses of diltiazem, metoprolol and amiodarone. We report a severe overdose of
      these drugs treated with HDI and IFE in a patient with hypertrophic
      cardiomyopathy (HCM). We also discuss the potential clinical implications of the
      inotropic effects of HDI in the setting of HCM and the use and efficacy of IFE in
      this overdose.

PMID- 21174186
TI  - Downregulation of STAT3 signaling induces apoptosis but also promotes anti
      apoptotic gene expression in human pancreatic cancer cell lines.
AB  - Signal transducer and activator of transcription 3 (STAT3) is a key regulator of
      cytokine signaling pathways that regulates gene expression. In pancreatic cancer,
      constitutive activation of STAT3 contributes to oncogenesis by preventing
      apoptosis through upregulation of anti-apoptotic proteins. We have examined the
      inhibition of STAT3 as a potential therapeutic approach in pancreatic cancer.
      siRNA targeting STAT3 was used to evaluate the role of STAT3 in modulating the
      expression of Survivin/BIRC5 and BCL-xL in the pancreatic cancer cell lines PANC
      1 and BxPC-3 and induction of apoptosis. Expression of STAT3, Survivin/BIRC5, and
      BCL-xL on mRNA and protein level was measured by real-time RT-PCR and Western
      blot analysis 24, 48, and 72 h after transfection. STAT3 downregulation resulted
      in a decrease of cell viability in both cell lines and induced apoptosis in BxPC
      3 cells. Despite significant inhibition of STAT3, the expression of the anti
      apoptotic genes Survivin/BIRC5 and BCL-xL were not subsequently downregulated.
      Even more, the cell line BxPC-3 shows a significant increase of Survivin/BIRC5
      and BCL-xL mRNA after 48-72 h as a result of STAT3 downregulation. Inactivation
      of STAT3 in pancreatic cancer cell lines induces apoptosis but also may promote
      the expression of anti-apoptotic genes.

PMID- 21174184
TI  - Identification and characterization of anesthetic targets by mouse molecular
      genetics approaches.
AB  - PURPOSE: It is now generally accepted that proteins are the primary targets of
      general anesthetics. However, the demonstration that the activity of a protein is
      altered by general anesthetics at clinically relevant concentrations in vitro
      does not provide direct evidence that this target mediates pharmacological
      actions of general anesthetics. Here we report on advances that have been made in
      identifying the contribution of individual ligand-gated ion channels to defined
      anesthetic endpoints using molecular mouse genetics. PRINCIPAL FINDINGS: Gamma
      aminobutyric acid (GABA)(A) receptor subtypes defined by the presence of the
      alpha1, alpha4, alpha5, beta2, and beta3 subunits and two-pore domain potassium
      channels (TASK-1, TASK-3, and TREK) have been discovered to mediate, at least in
      part, the hypnotic, immobilizing or amnestic actions of intravenous and volatile
      general anesthetics. Moreover, using tissues from genetically modified mice,
      specific functions of GABA(A) receptor subtypes in cortical and spinal neuronal
      networks were identified. CONCLUSION: Genetically modified mice have been very
      useful for research on mechanisms of anesthesia and have contributed to the
      functional identification of general anesthetic targets and of the role of these
      targets in neuronal networks.

PMID- 21174188
TI  - Introduction: special issue JIMB-BioMicroWorld 2009.

PMID- 21174187
TI  - Improved numerical modelling of heat transfer in human tissue exposed to RF
      energy.
AB  - A novel numerical model to simulate thermal response of human body tissues
      exposed to RF energy is presented in this article. It is based on a new algorithm
      for the construction of a realistic blood vessel network, a new model of blood
      flow velocity distribution and an approach to solve the bio-heat equation in
      human tissue with variable and initially unknown blood temperature distribution.
      The algorithm generates a discrete 3D representation of both arterial and venous
      vascular networks and a continuous blood velocity vector field for arbitrary
      enclosed geometries required to represent the complex anatomy of human body and
      blood flow. The results obtained in this article by applying the developed method
      to realistic exposure conditions demonstrates relative difference in thermal
      response of the exposed tissue compared to results obtained by conventional bio
      heat equation with constant blood perfusion and temperature. The developed
      technique may provide more accurate and realistic modelling in thermal dosimetry
      studies of human body RF exposure.

PMID- 21174189
TI  - Built environment influences on healthy transportation choices: bicycling versus
      driving.
AB  - A growing body of evidence links the built environment to physical activity
      levels, health outcomes, and transportation behaviors. However, little of this
      research has focused on cycling, a sustainable transportation option with great
      potential for growth in North America. This study examines associations between
      decisions to bicycle (versus drive) and the built environment, with explicit
      consideration of three different spatial zones that may be relevant in travel
      behavior: trip origins, trip destinations, and along the route between. We
      analyzed 3,280 utilitarian bicycle and car trips in Metro Vancouver, Canada made
      by 1,902 adults, including both current and potential cyclists. Objective
      measures were developed for built environment characteristics related to the
      physical environment, land use patterns, the road network, and bicycle-specific
      facilities. Multilevel logistic regression was used to model the likelihood that
      a trip was made by bicycle, adjusting for trip distance and personal
      demographics. Separate models were constructed for each spatial zone, and a
      global model examined the relative influence of the three zones. In total, 31%
      (1,023 out of 3,280) of trips were made by bicycle. Increased odds of bicycling
      were associated with less hilliness; higher intersection density; less highways
      and arterials; presence of bicycle signage, traffic calming, and cyclist
      activated traffic lights; more neighborhood commercial, educational, and
      industrial land uses; greater land use mix; and higher population density.
      Different factors were important within each spatial zone. Overall, the
      characteristics of routes were more influential than origin or destination
      characteristics. These findings indicate that the built environment has a
      significant influence on healthy travel decisions, and spatial context is
      important. Future research should explicitly consider relevant spatial zones when
      investigating the relationship between physical activity and urban form.

PMID- 21174190
TI  - [Urinary tract infections after kidney transplantation: Essen algorithm for
      calculated antibiotic treatment].
AB  - Urinary tract infections are the most common infection early after
      transplantation and can affect long-term graft function. Any urinary tract
      infection in renal transplant recipients should be seen as "complex" with regard
      to consequences for diagnosis and therapy. The increase in resistance to anti
      infective agents seen among uropathogens is one of the central therapeutic
      problems. This means for routine clinical practice that contact isolation
      precautions should be consistently implemented for affected patients and the
      duration of introducing urinary tract instruments should be minimized. Detection
      of pyuria and urine cultures are required to confirm infection, to identify the
      corresponding pathogen, and to review the antibiotic therapy.The "Essen algorithm
      for calculated antibiotic treatment of urinary tract infections in renal
      transplant patients" takes into consideration the high incidence of Gram-negative
      pathogens in general and the increased incidence of enterococci in the early
      phase after transplantation. Within the first 2 months after transplantation
      quinolones should be used and later cephalosporins. In case of urosepsis,
      calculated antibiotic therapy should cover problematic Gram-negative pathogens
      such as pseudomonades. The calculated antibiotic therapy should be administered
      intravenously in severe infections. In any case the local and regional antibiotic
      susceptibility should be taken into account when deciding on the calculated
      antibiotic therapy.

PMID- 21174192
TI  - Ligand exchange chromatography: a vital dimension for the reliable
      characterization of heterocycles in crude oils and refined products.
AB  - In the present study, we established a statistical distribution pattern of
      indigenous sulfur, nitrogen, and oxygen species in Arabian Heavy crude oil and
      its distilled fractions: naphtha, gas oil, and vacuum gas oil (VGO) using
      chemical derivatization with methyl iodide and subsequent characterization by
      positive electrospray Fourier transform mass spectrometry. It was observed that
      sulfur species for naphtha and gas oil were accumulated at lower double bond
      equivalent values and at lower carbon numbers compared to VGO, whereas crude oil
      encompassed a complete range of the sulfur species detected in all distilled
      fractions. Moreover, the use of alumina column chromatography and ligand exchange
      chromatography (LEC) on a palladium-bonded silica stationary phase revealed
      additional structural features of sulfur heterocycles in terms of condensed and
      non-condensed thiophenes. During LEC separation, in addition to sulfur
      heterocycles, interesting results were obtained for oxygen-containing compounds.
      Ortho-substituted alkyl phenols were separated from meta- and para-substituted
      alkyl phenols on a palladium-bonded silica stationary phase.

PMID- 21174191
TI  - Increasing age- and sex-specific rates of hip fracture in Mexico: a survey of the
      Mexican Institute of Social Security.
AB  - This study, characterising the incidence of hip fracture in Mexico, showed that
      age- and sex-specific rates increased between 2000 and 2006. The demographic
      changes estimated for Mexico indicate that the annual number of hip fractures
      will rise from 29,732 in 2005 to 155,874 in 2050. If the age-specific incidence
      of hip fracture continues, the number of hip fractures would increase by a
      further 46%. INTRODUCTION: The aim of the present study was to determine time
      trends, if any, in hip fracture rates for Mexico and to forecast the number of
      hip fractures expected in Mexico over the coming years up to 2050. METHODS: All
      hip fracture cases registered during the years 2000-2006 were collected at all
      the second and tertiary-care hospitals across the country from one of the largest
      health systems in Mexico, The Instituto Mexicano del Seguro Social (IMSS).
      RESULTS: Between the years 2000 and 2006, the age-specific incidence of hip
      fracture increased significantly both for men and women by 1% per year (p = 0.016
      and p < 0.001, respectively). In 2005, there were there were 29,732 hip fractures
      estimated in Mexico, 68% of which were found in women. Assuming no change in the
      age- and sex-specific incidence of hip fracture, the number of hip fractures was
      expected to increase markedly with time to 155,874 in 2050. Assuming that the age
      specific incidence continues, the number of hip fractures in men and women would
      increase by a further 46% to 226,886 in 2050. CONCLUSION: Demographic changes
      estimated for Mexico indicate that the annual number of hip fractures will rise
      from 29,732 in 2005 to 155,874 expected in 2050. If the age-specific incidence of
      hip fracture continues to rise, the number of hip fractures would increase by a
      further 46%.

PMID- 21174193
TI  - Performance evaluation of Mimetic LigandTM B14-triazole-FractoAIMs adsorbents for
      the capture of human monoclonal immunoglobulin G from cell culture feed.
AB  - The new affinity-type Mimetic LigandTM B14 was coupled with a 1,2-diaminoethane
      spacer (2LP) and a [1,2,3]-triazole spacer (TRZ) to three different support
      media. In addition to the agarose-based PuraBead and the polymethacrylate-type
      Fractogel, three new polymeric support media were introduced, the FractoAIMs 1,
      2, and 3 (FA1, FA2, and FA3). These new FA supports differ in pore size as well
      as density of epoxide groups. The immobilization of the B14-ligand onto an azide
      group-modified surface was performed with a copper (I)-mediated Click reaction.
      The IgG capture performance was tested for various ligand-spacer support
      combinations using cell culture feed containing human immunoglobulin G(1)
      (hIgG(1)). The most promising adsorbent, B14-TRZ-FA3, was further optimized by
      improving the surface chemistry through a triple endcapping concept employing an
      improved Click reaction protocol. This new technique enabled the most efficient
      deactivation of residual azide groups. In a direct comparison with a commercially
      available Protein A media, B14-TRZ-FA3 3* ec provided superior results at fast
      flow-rates and low bed-height. Dynamic binding capacities of 11.4 g/L for 10%
      breakthrough of hIgG(1), elution capacities of 16.0 g/L hIgG(1) and a recovery of
      86% were achieved. The same results were obtained for a dialyzed and pre-purified
      feed solution, which is a clear indicator that triple-endcapped affinity support
      surfaces are practically inert to the non-specific binding of host cell proteins.

PMID- 21174194
TI  - Dispersive liquid-liquid microextraction based on the solidification of a
      floating organic droplet for simultaneous analysis of diethofencarb and
      pyrimethanil in apple pulp and peel.
AB  - A method for analysis of diethofencarb and pyrimethanil in apple pulp and peel
      was developed by using dispersive liquid-liquid microextraction based on
      solidification of a floating organic droplet (DLLME-SFO) and high-performance
      liquid chromatography with diode-array detection (HPLC-DAD). Acetonitrile was
      used as the solvent to extract the two fungicides from apple pulp and peel,
      assisted by microwave irradiation. When the extraction process was finished, the
      target analytes in the extraction solvent were rapidly transferred from the
      acetonitrile extract to another extraction solvent (1-undecanol) by using DLLME
      SFO. Because of the lower density of 1-undecanol than that of water, the finely
      dispersed droplets of 1-undecanol collected on the top of aqueous sample and
      solidified at low temperature. Meanwhile, the tiny particles of apple cooled and
      precipitated. Recovery was tested for a concentration of 8 MUg kg-1. Recovery of
      diethofencarb and pyrimethanil from apple pulp and peel was in the range 83.5
      101.3%. The repeatability of the method, expressed as relative standard
      deviation, varied between 4.8 and 8.3% (n = 6). Detection limits of the method
      for apple pulp and peel varied from 1.2-1.6 MUg kg-1 for the two fungicides.
      Compared with conventional sample preparation, the method has the advantage of
      rapid speed and simple operation, and has high enrichment factors and low
      consumption of organic solvent.

PMID- 21174195
TI  - Nanoparticles for the development of improved (bio)sensing systems.
AB  - Nanoparticles serve as fundamental building blocks for nanobiotechnology,
      especially in several applications in the development of novel (bio)sensing
      systems. Nanoparticles can be used for modification of the surfaces of
      (bio)sensing transducers or as optical or electroactive labels to improve
      different aspects of performance, for example sensitivity, detection limit,
      multidetection capability, and response stability. Nanoparticles can be
      integrated into the transducer materials on an individual basis or inside other
      matrices to ensure the immobilization of recognition biomolecules and/or
      receptors which are the principal components of the (bio)sensing systems.
      Incorporation of nanoparticles into optical and electrochemical (bio)sensing
      systems, including their use in microfluidic based systems has the advantages of
      enabling the design of robust, easy to use, portable, and cost-effective devices.

PMID- 21174196
TI  - Development of a fully automated toxicological LC-MS(n) screening system in urine
      using online extraction with turbulent flow chromatography.
AB  - In clinical toxicology, fast and specific methods are necessary for the screening
      of different classes of drugs. Therefore, an online extraction high-performance
      liquid chromatography coupled to mass spectrometry (LC-MS(n)) screening method
      using a MS(2) and MS(3) spectral library for the identification of xenobiotic
      substances has been developed and validated. Samples were run twice, once native
      and once after enzymatic hydrolysis. Internal standards and buffer were added to
      the urine samples. Following centrifugation, the supernatant was injected into
      the system. Extraction was performed by online turbulent flow chromatography. The
      chromatographic separation was achieved using a Phenyl/Hexyl column. For
      detection, a linear ion trap, equipped with an APCI interface, was used and the
      different compounds were identified using a MS(2) and MS(3) spectral library
      containing 356 compounds. The turnaround time to report the results of the
      screening including hydrolysis was approximately 2 h. About 92% of the 356
      substances could be identified with a limit of identification below 100 ng/ml.
      The recovery and matrix effect experiments showed suitable results, and in six
      drug-free urine samples of healthy volunteers analyzed for selectivity, no
      substances have been identified. Carryover could be well controlled, and the
      method had a good reproducibility. The comparison of the results of 103 real
      patient urine samples showed a good agreement between the existing GC-MS and LC
      MS methods with offline extraction and the new online extraction LC-MS(n)
      screening method. The presented method allows a fast and sensitive analysis of a
      broad range of compounds.

PMID- 21174197
TI  - In situ detection of aromatic compounds with biosensor Pseudomonas putida cells
      preserved and delivered to soil in water-soluble gelatin capsules.
AB  - While many types of bacteria have been engineered to produce an optical output in
      response to given analytes in a culture, their use for extensive, in situ
      monitoring of distinct chemical species in soil is hampered by a dearth of
      practicable spreading schemes. In this work, we report and validate a
      comprehensive system for the long-term preservation of Pseudomonas putida cells
      genetically designed for biosensing benzene, toluene, ethylbenzene, and xylenes
      (BTEX) in soil, along with a procedure to formulate, spread, and vigorously
      activate such bacteria at the desired site and occasion. To this end, various
      known lyoprotectants were tested for promoting the long-term maintenance of
      biosensor cells with quite variable outcomes. While a formulation of inositol and
      maltodextrines was optimal for preservation of freeze-dried BTEX-sensing
      bacteria, adsorption of P. putida cells to corncob powder (an abundant residue of
      the corn industry) endowed the resulting material with a lasting viability at
      ambient conditions. In any case, the thereby preserved bacterial biomass acquired
      physical and mechanical properties adequate for formulating the biosensor agent
      in water-soluble but otherwise hard dry gelatine capsules with a long shelf life.
      When such capsules were spread in a soil microcosm and subsequently liquefied
      with water or high humidity, the released microorganisms formed spots that gave
      an intense luminiscent signal upon exposure to effectors of the sensor circuit
      implanted in the chromosome of the P. putida strain. We argue that the procedures
      described here can facilitate implementation of wide-area biological detection
      strategies for revealing the location of toxic or perilous chemicals.

PMID- 21174198
TI  - Characterisation of workplace aerosols in the manganese alloy production industry
      by electron microscopy.
AB  - Workplace aerosols in a combined FeMn and SiMn alloy smelter were studied by
      scanning and transmission electron microscopy. Special emphasis was placed on the
      characterisation of individual particles with diameters below 500 nm and on
      identification of the different manganese phases present in the workroom air. In
      high-carbon FeMn production, the submicron size fraction is dominated by MnO
      particles forming chain-like or compact agglomerates. Minor amounts of MnO(2),
      Mn(3)O(4), Mn(2)O(3) and Fe(3)O(4) are also observed. During production of SiMn,
      the submicron size fraction consists predominantly of MnSi particles, but small
      amounts of Mn(3)Si, Mn(6)Si and Mn(5)Si(2) are also found. Workplace aerosols
      from the manganese oxide refinement (MOR) process consist mostly of Mn oxides.
      Minor amounts of carbonaceous particles occurring as sheets, ribbons and as
      hollow carbon structures are observed along the whole production line.
      Carbonaceous particles are either amorphous or consist of poorly crystallised
      graphite. Particles with fibre morphology were encountered at all sampling
      locations but most prominently during tapping of FeMn with fibre concentrations
      between 0.1 and 0.7 per cm(3). The pronounced differences in particle composition
      along the production line clearly show that workers are exposed to a variety of
      Mn-containing species. MnO particles have a higher solubility than MnSi particles
      and are thus more bioaccessible, suggesting a higher risk of adverse health
      effects in the FeMn production than in the SiMn production.

PMID- 21174199
TI  - High-throughput profiling of N-linked oligosaccharides in therapeutic antibodies
      using a microfluidic CD platform and MALDI-MS.
AB  - Recombinant therapeutic antibodies have shown a great potential in the treatment
      of several severe medical conditions such as cancer and autoimmune diseases.
      Glycosylation plays a critical role in biological activity and immunogenic
      properties of these compounds. The analysis of glycan profiles is therefore
      necessary in many steps of the development and manufacturing process from early
      development to quality control of the final product. In this paper, a fast,
      parallel, and robust sample preparation platform for glycosylation profiling
      using a microfluidic compact disc (CD) is presented. A sequential process
      including selective capture of antibody from a crude cell supernatant using
      protein A beads, enzymatic release of glycans, purification with a graphitized
      carbon black column, and crystallisation for MALDI-TOF analysis were performed on
      the CD. Glycosylation profiles of an antibody intended for therapeutic use
      produced in two different cell lines were compared.

PMID- 21174200
TI  - Trilinearity and component interaction constraints in the multivariate curve
      resolution investigation of NO and O3 pollution in Barcelona.
AB  - Multiway and multiset data analysis extensions of the multivariate curve
      resolution alternating least squares (MCR-ALS) method are proposed for the
      investigation of the temporal distribution of the pollution by nitric oxide (NO)
      and ozone (O(3)) in one sampling station in the urban centre of Barcelona
      (Catalonia, Spain), during the years 2000-2006. Different specific studies were
      performed considering the annual and pluriannual contamination by these two
      contaminants, individually or in combination using different data matrix
      augmentation strategies and multiway and multiset data analysis models. Daily,
      hourly and annual profiles were estimated describing different patterns and
      summarising the main contamination processes. The daily and night trends found
      were mainly attributed to traffic and photochemical processes favoured by light
      radiation. Moreover, winter-summer seasonal trends were also clearly detected and
      their changes over different years assessed. The extension MCR-ALS method to
      multiset data analysis using different constraints like non-negativity,
      trilinearity and interaction among components is confirmed to be a powerful
      method to improve the interpretability of the different contamination patterns in
      atmospheric contamination studies.

PMID- 21174201
TI  - Detoxification of AM-241 solutions by humic substances: bioluminescent
      monitoring.
AB  - The study addresses the effect of humic substances on marine luminous bacteria
      Photobacterium phosphoreum exposed to Am-241 (3,000 Bq L(-1), water solution).
      Luminescent intensity of the bacteria was applied as a marker of their
      physiological activity. Humic substances have been found to reduce the effect of
      Am-241 on luminescence, decrease damage to cells, and change distribution of Am
      241 between bacterial cells and intercellular media. It was shown that water
      soluble humic substances, being products of natural transformation of organic
      substances in soil and bottom sediments, can serve as protecting agents for water
      microorganisms exposed to alpha radionuclides.

PMID- 21174202
TI  - Volumetric analysis of corticocancellous bones using CT data.
AB  - OBJECTIVE: To present a method for an automated volumetric analysis of
      corticocancellous bones such as the superior pubic ramus using CT data and to
      assess the reliability of this method. MATERIALS AND METHODS: Computed tomography
      scans of a consecutive series of 250 patients were analyzed. A Hounsfield unit
      (HU) thresholding-based reconstruction technique ("Vessel Tracking," GE
      Healthcare) was used. A contiguous space of cancellous bone with similar HU
      values between the starting and end points was automatically identified as the
      region of interest. The identification was based upon the density gradient to the
      adjacent cortical bone. The starting point was defined as the middle of the
      parasymphyseal corticocancellous transition zone on the axial slice showing the
      parasymphyseal superior pubic ramus in its maximum anteroposterior width. The end
      point was defined as the middle of the periarticular corticocancellous transition
      zone on the axial slice showing the quadrilateral plate as a thin cortical plate.
      The following parameters were automatically obtained on both sides: length of the
      center line, volume of the superior pubic ramus between the starting point and
      end point, minimum, maximum and mean diameter perpendicular to the center line,
      and mean cross-sectional area perpendicular to the center line. RESULTS: An
      automated analysis without manual adjustments was successful in 207 patients
      (82.8%). The center line showed a significantly greater length in female patients
      (67.6 mm vs 65.0 mm). The volume was greater in male patients (21.8 cm(3) vs 19.4
      cm(3)). The intersite reliability was high with a mean difference between the
      left and right sides of between 0.1% (cross-sectional area) and 2.3% (volume).
      CONCLUSIONS: The method presented allows for an automated volumetric analysis of
      a corticocancellous bone using CT data. The method is intended to provide
      preoperative information for the use of intramedullary devices in fracture
      fixation and percutaneous cement augmentation techniques.

PMID- 21174203
TI  - High-grade intra-articular liposarcoma of the knee.
AB  - A high-grade pleomorphic intra-articular liposarcoma of the knee is described in
      a 48-year-old man, which was diagnosed histologically after arthroscopy of the
      knee for suspected pigmented villonodular synovitis (PVNS). The patient proceeded
      to undergo an extra-articular resection with a custom-made prosthesis. This
      report highlights the need to remember this rare tumour in the differential
      diagnosis of atypical soft tissue lesions within the knee joint prior to
      instrumentation.

PMID- 21174208
TI  - Nine years follow-up of 100 ceramic-on-ceramic total hip arthroplasty.
AB  - The aim of this study was to evaluate the first 100 cementless ceramic-on-ceramic
      total hip arthroplasty (THA) performed at our institution with more than nine
      years of follow-up. Clinical evaluation was performed using Harris hip score.
      Radiological evaluation was performed by two surgeons. Four patients were lost to
      follow-up. Harris hip score significantly improved at latest follow-up.
      Radiological analysis showed calcar osteolysis for 75 patients and one cup
      loosening. One patient required a revision five years postoperatively for cup
      loosening. Based on these results and the routine use of a navigation system to
      optimise positioning of the implants, we advocate the use of uncemented
      hydroxyapatite coated ceramic-on-ceramic THA in young and active patients in our
      current practice.

PMID- 21174209
TI  - Effects of cold pressor-induced sympathetic stimulation on the mechanical
      properties of common carotid and femoral arteries in healthy males.
AB  - Our aim was to evaluate the effects of sympathetic excitation and elevation of
      blood pressure on mechanical properties of common carotid and femoral arteries by
      wave intensity analysis (WIA). The diameters and arterial stiffness parameters of
      right common carotid artery (RCCA) and right common femoral artery (RCFA) in
      healthy young men were measured by WIA at baseline and during cold pressor test
      (CPT). In addition, the blood pressure and heart rate were recorded
      simultaneously. The heart rates and blood pressures increased during CPT compared
      with baseline, while the pulse pressures remained unchanged. The diameters of
      RCCA increased slightly, while those of RCFA did not change. The Peterson's
      pressure modulus (Ep), augment index (AI), and pulse wave velocity from beta
      (PWVbeta) increased obviously, while arterial compliance (AC) decreased with no
      change in stiffness index (beta) of both arteries during CPT when compared with
      baseline. There was an obvious increase in pulse wave velocity from wave
      intensity (PWV_WI) of RCCA, while the PWV_WI of RCFA showed no significant change
      during CPT. The sympathetic nervous system exerts a more marked tonic restraint
      on RCFA than on RCCA. The Ep, AC, AI, PWVbeta of RCCA, and RCFA are much affected
      by variations in blood pressure and sympathetic status, while the beta of both
      arteries are less vulnerable to these factors and are more reliable in reflecting
      the actual arterial stiffness; The PWV_WI appears to be suitable only for
      evaluating the stiffness of RCCA instead of RCFA.

PMID- 21174210
TI  - Ischemia/reperfusion injury is increased and cardioprotection by a
      postconditioning protocol is lost as cardiac hypertrophy develops in nandrolone
      treated rats.
AB  - We hypothesized that nandrolone (ND)-abuse induces cardiac hypertrophy, increases
      myocardial susceptibility to ischemia/reperfusion (I/R) injury, and reduces
      responsiveness to postconditioning (PostC) cardioprotection. Wistar-rats were ND
      treated for 2 weeks (short_ND) or 10 weeks (long_ND). Vehicle-treated rats served
      as controls. Hearts were retrogradely perfused and left ventricular pressure
      (LVP) was measured before and after 30-min global ischemia. In subgroups of
      hearts, to induce cardioprotection a PostC protocol (five cycles of 10-s
      reperfusion and 10-s ischemia) was performed. beta-adrenoreceptors, kinases (Akt
      and GSK-3beta) and phosphatases (PP2A sub A and PP2A sub B) were examined by
      Western blot before and after ischemia. After 120-min reperfusion, infarct size
      was measured. Short_ND slightly increased cardiac/body weight ratio, but did not
      affect cardiac baseline nor post-ischemic contractile function or infarct size
      when compared to vehicle hearts. However, PostC limited cardiac dysfunction much
      more in short_ND hearts than the other groups. Although cardiac/body weight ratio
      markedly increased after long_ND, baseline LVP was not affected. Yet, post
      ischemic contracture and infarct size were exacerbated and PostC was unable to
      reduce infarct size and ventricular dysfunction. While short_ND increased
      phosphatases, non-phosphorylated and phosphorylated Akt, long_ND reduced
      phosphatase-expression and Akt phosphorylation. Both short_ND and long_ND had no
      effect on the GSK-3beta-phosphorylation but increased the expression of beta(2)
      adrenoreceptors. In reperfusion, PostC increased Akt phosphorylation regardless
      of protective effects, but reduced phosphatase-expression in protected hearts
      only. In conclusion, short_ND improves post-ischemic myocardial performance in
      postconditioned hearts. However, long_ND increases myocardial susceptibility to
      I/R injury and abolishes cardioprotection by PostC. This increased susceptibility
      might be related to steroid-induced hypertrophy and/or to altered enzyme
      expression/phosphorylation.

PMID- 21174211
TI  - Differential chemokine receptor expression regulates functional specialization of
      endothelial progenitor cell subpopulations.
AB  - Postnatal vasculogenesis is mediated by endothelial progenitor cells (EPCs) which
      consist of subpopulations with different functional capacities. Our goal was to
      profile chemokine receptor expression on relevant subsets of EPCs and to
      characterize their role for effector functions. CD34(+)/CD133(+)/VEGFR2(+) EPCs
      were characterized by high expression of chemokine receptors CXCR4, CX3CR1, BLT1,
      and low level expression of CXCR2 and CCR2, while primordial CD34(
      )/CD133(+)/VEGFR2(+) EPCs express these chemokine receptors at comparably low
      levels. Migration assays revealed that SDF-1, fractalkine, and LTB4 significantly
      increase migration of CD34(-)/CD133(+)/VEGFR2(+) EPCs, while SDF-1 was the only
      potent agonist of migration of CD34(+)/CD133(+)/VEGFR2(+) EPCs. SDF-1,
      fractalkine, and LTB4 trigger significant increase adhesion of
      CD34(+)/CD133(+)/VEGFR2(+) EPCs, while in CD34(-)/CD133(+)/VEGFR2(+) EPCs SDF-1
      and fractalkine are equipotent agonists and LTB4 triggers a smaller though still
      significant increase in adhesion. Differential expression of specific chemokine
      receptors is an important regulator in terms of migration and adhesion of
      biologically relevant EPC-subpopulations, which may have implications for cell
      therapeutic strategies for treatment of ischemic vascular disease.

PMID- 21174212
TI  - Oncostatin M-enhanced vascular endothelial growth factor expression in human
      vascular smooth muscle cells involves PI3K-, p38 MAPK-, Erk1/2- and STAT1/STAT3
      dependent pathways and is attenuated by interferon-gamma.
AB  - The pleiotropic cytokine oncostatin M (OSM), a member of the glycoprotein (gp)130
      ligand family, plays a key role in inflammation and cardiovascular disease. As
      inflammation precedes and accompanies pathological angiogenesis, we investigated
      the effect of OSM and other gp130 ligands on vascular endothelial growth factor
      (VEGF) production in human vascular smooth muscle cells (SMC). Human coronary
      artery SMC (HCASMC) and human aortic SMC (HASMC) were treated with different
      gp130 ligands. VEGF protein was determined by ELISA. Specific mRNA was detected
      by RT-PCR. Western blotting was performed for signal transducers and activators
      of transcription1 (STAT1), STAT3, Akt and p38 mitogen-activated protein kinase
      (p38 MAPK). OSM mRNA and VEGF mRNA expression was analyzed in human carotid
      endaterectomy specimens from 15 patients. OSM increased VEGF production in both
      HCASMC and HASMC derived from different donors. OSM upregulated VEGF and OSM
      receptor-specific mRNA in these cells. STAT3 inhibitor WP1066, p38 MAPK
      inhibitors SB-202190 and BIRB 0796, extracellular signal-regulated kinase1/2
      (Erk1/2) inhibitor U0126, and phosphatidylinositol 3-kinase (PI3K) inhibitors LY
      294002 and PI-103 reduced OSM-induced VEGF synthesis. We found OSM expression in
      human atherosclerotic lesions where OSM mRNA correlated with VEGF mRNA
      expression. Interferon-gamma (IFN-gamma), but not IL-4 or IL-10, reduced OSM
      induced VEGF production in vascular SMC. Our findings that OSM, which is present
      in human atherosclerotic lesions and correlates with VEGF expression, stimulates
      production of VEGF by human coronary artery and aortic SMC indicate that OSM
      could contribute to plaque angiogenesis and destabilization. IFN-gamma reduced
      OSM-induced VEGF production by vascular SMC.

PMID- 21174213
TI  - Diastolic dysfunction and arrhythmias caused by overexpression of CaMKIIdelta(C)
      can be reversed by inhibition of late Na(+) current.
AB  - Transgenic (TG) Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) delta(C)
      mice develop systolic heart failure (HF). CaMKII regulates intracellular Ca(2+)
      handling proteins as well as sarcolemmal Na(+) channels. We hypothesized that
      CaMKII also contributes to diastolic dysfunction and arrhythmias via augmentation
      of the late Na(+) current (late I(Na)) in early HF (8-week-old TG mice).
      Echocardiography revealed severe diastolic dysfunction in addition to decreased
      systolic ejection fraction. Premature arrhythmogenic contractions (PACs) in
      isolated isometrically twitching papillary muscles only occurred in TG
      preparations (5 vs. 0, P < 0.05) which could be completely terminated when
      treated with the late I(Na) inhibitor ranolazine (Ran, 5 MUmol/L). Force
      frequency relationships revealed significantly reduced twitch force amplitudes in
      TG papillary muscles. Most importantly, diastolic tension increased with raising
      frequencies to a greater extent in TG papillary muscles compared to WT specimen
      (at 10 Hz: 3.7 +/- 0.4 vs. 2.5 +/- 0.3 mN/mm2; P < 0.05). Addition of Ran
      improved diastolic dysfunction to 2.1 +/- 0.2 mN/mm2 (at 10 Hz; P < 0.05) without
      negative inotropic effects. Mechanistically, the late I(Na) was markedly elevated
      in myocytes isolated from TG mice and could be completely reversed by Ran. In
      conclusion, our results show for the first time that TG CaMKIIdelta(C)
      overexpression induces diastolic dysfunction and arrhythmogenic triggers possibly
      via an enhanced late I(Na). Inhibition of elevated late I(Na) had beneficial
      effects on arrhythmias as well as diastolic function in papillary muscles from
      CaMKIIdelta(C) TG mice. Thus, late I(Na) inhibition appears to be a promising
      option for diastolic dysfunction and arrhythmias in HF where CaMKII is found to
      be increased.

PMID- 21174215
TI  - Chronic pancreatitis: modern surgical management.
AB  - INTRODUCTION: Chronic pancreatitis (CP) is a disease with enormous social and
      personal impact. It is most commonly caused by the abuse of alcohol combined with
      nicotine. CP is usually characterised by an inflammatory mass located in the
      pancreatic head. Its natural course is characterised by persistent or recurrent
      painful attacks as well as progressive loss of pancreatic function due to
      fibrosis of the parenchyma with consecutive endocrine and exocrine insufficiency.
      CONCLUSIONS: The only success parameter of any treatment is the effective long
      lasting pain relief and improvement in the quality of life. The surgical
      armamentarium includes simple drainage procedures, resections of different
      extents or a combination of both. Duodenum-preserving resection of the pancreas
      offers the best short-term outcome according to trials conducted so far. It has
      the benefit of combining the highest safety with the highest efficiency.
      Additionally, the extent of the operation can be adapted to the morphology of the
      individual patient.

PMID- 21174216
TI  - Meta-analysis of the association between VEGF-634 G>C and risk of malignancy
      based on 23 case-control studies.
AB  - PURPOSE: The association between polymorphism of vascular endothelial growth
      factor (VEGF)-634 G>C and malignancy risk has been widely studied, and no
      conclusive result was available up to now. METHODS: Twenty-three case-control
      studies with 21,917 individuals were included in this meta-analysis through
      searching the databases of Medline, Embase, and CNKI (up to October 1st, 2010).
      The odds ratio (OR) and 95% confidence interval (95%CI) were used to investigate
      the strength of the association. RESULTS: Overall, the pooled analysis showed
      that there was no association between VEGF-634 G>C and risk of malignancy, and
      the ORs (95%CIs) were 0.98 (0.85-1.12) for GG versus CC, 1.03 (0.90-1.17) for GC
      versus CC, 1.00 (0.89-1.13) for G carrier versus CC, and 1.08 (0.94-1.23) for C
      carrier versus GG. Subgroup analyses according to ethnicity, source of control,
      type of cancer, and sample size were also performed, and results indicated that
      VEGF-634 G>C was not associated with risk of malignancy for neither Asians [1.06
      (0.81-1.38) for GG vs. CC and 1.08 (0.84-1.39) for GC vs. CC] nor Caucasians
      [0.93 (0.83-1.05) for GG vs. CC and 0.98 (0.87-1.10) for GC vs. CC]. It was also
      not associated with risk of breast cancer [0.95 (0.81-1.12) for GG vs. CC],
      gastric cancer [0.93 (0.47-1.84) for GG vs. CC], and colorectal cancer [1.17
      (0.93-1.47) for GG vs. CC]. CONCLUSIONS: This meta-analysis suggests that VEGF
      634 G>C may be not associated with risk of malignancy. More studies with larger
      sample size were needed to provide more precise evidence.

PMID- 21174214
TI  - Double-strand breaks and the concept of short- and long-term epigenetic memory.
AB  - Double-strand breaks represent an extremely cytolethal form of DNA damage and
      thus pose a serious threat to the preservation of genetic and epigenetic
      information. Though it is well-known that double-strand breaks such as those
      generated by ionising radiation are among the principal causative factors behind
      mutations, chromosomal aberrations, genetic instability and carcinogenesis,
      significantly less is known about the epigenetic consequences of double-strand
      break formation and repair for carcinogenesis. Double-strand break repair is a
      highly coordinated process that requires the unravelling of the compacted
      chromatin structure to facilitate repair machinery access and then restoration of
      the original undamaged chromatin state. Recent experimental findings have pointed
      to a potential mechanism for double-strand break-induced epigenetic silencing.
      This review will discuss some of the key epigenetic regulatory processes involved
      in double-strand break (DSB) repair and how incomplete or incorrect restoration
      of chromatin structure can leave a DSB-induced epigenetic memory of damage with
      potentially pathological repercussions.

PMID- 21174217
TI  - Fetal environment, epigenetics, and pediatric renal disease.
AB  - The notion that some adult diseases may have their origins in utero has recently
      captured scientists' attention. Some of these effects persist across generations
      and may involve epigenetic mechanisms. Epigenetic modifications, DNA methylation
      together with covalent modifications of histones, alter chromatin density and
      accessibility of DNA to cellular machinery, modulating the transcriptional
      potential of the underlying DNA sequence. Here, we will discuss the different
      epigenetic modifications and their potential role in and contribution to renal
      disease development.

PMID- 21174218
TI  - Primary versus secondary hypertension in children followed up at an outpatient
      tertiary unit.
AB  - Childhood hypertension has classically been recognized as a secondary disease.
      However, primary hypertension also occurs in children. The aim of this study was
      to compare clinical features of pediatric patients with elevated blood pressure,
      which were referred to an outpatient tertiary unit, and to detect variables
      associated with the identification of primary hypertension. The records of 220
      patients with hypertension followed between 1996 and 2006 were analyzed. The
      variable of interest was primary hypertension. Logistic regression analysis was
      applied to identify clinical variables that were independently associated with
      primary hypertension. Of 220 patients, 33 (15%) had primary hypertension, and 187
      (85%) exhibited secondary hypertension. No statistically significant differences
      were detected in gender, race, age at diagnosis, and systolic/diastolic blood
      pressure levels between both groups. After adjustment, four variables at baseline
      remained independently associated with primary hypertension: absence of
      signs/symptoms (OR 18.87, 95% CI 6.32-56.29), normal serum creatinine (OR 0.02,
      95% CI 0.00-0.27), family history of hypertension (OR 3.03, 95% CI 1.04-8.79),
      and elevated body weight (OR 1.06, 95% CI 1.02-1.10). The absence of
      signs/symptoms, normal serum creatinine, family history of hypertension, and
      overweight/obesity at admission are clues to diagnose primary hypertension in
      childhood.

PMID- 21174219
TI  - Single daily high-dose mizoribine therapy for children with steroid-dependent
      nephrotic syndrome prior to cyclosporine administration.
AB  - Although cyclosporine (CsA) therapy is effective in the management of children
      with steroid-dependent nephrotic syndrome (SDNS), a recent study has revealed
      that the use of CsA itself was a significant predictor of NS relapse in
      adulthood. The efficacy of single daily high-dose mizoribine (MZR) therapy was
      assessed in 10 children with SDNS (mean age, 6.2 years) who had never been
      treated with CsA previously. MZR was started at 5 mg/kg, administered as a single
      daily dose after breakfast, and the dose was adjusted to achieve 2-h post-dose
      MZR levels (C2) of approximately 3 MUg/ml. In 9 of the 10 patients, treatment
      with a single daily dose of MZR (mean dose, 8.4 mg/kg/day) over a period of 22
      months (median) resulted in significant reduction of the mean prednisolone dose
      from 0.39 to 0.15 mg/kg/day and the median 12-month relapse rate from 3.0 to 0.4
      episodes/12 months. Although cyclophosphamide was initiated in one patient
      because of treatment failure, none of the 10 patients required treatment with CsA
      during the observation period (median, 33 months). These data indicate that
      single daily high-dose MZR therapy is possibly useful in treating children with
      SDNS and that it may also eliminate the need for CsA in some patients.

PMID- 21174220
TI  - Comments on use of a Parker Flex-Tip tube((r)) to facilitate intubation with the
      Pentax-AWS((r)).

PMID- 21174221
TI  - Psychiatric disorders in children and adolescents presenting with unexplained
      chronic pain: what is the prevalence and clinical relevancy?
AB  - The prevalence of psychiatric disorders among children with unexplained chronic
      pain (UCP) is high in unselected populations and pain clinics, yet the clinical
      relevance of these disorders in children referred for unexplained pain is not
      known. This study assessed the prevalence of clinically relevant psychiatric
      disorders and their predictors in children referred to a children's hospital for
      UCP. Psychiatry morbidity was assessed in 134 children, aged 8-17 years, using
      the Diagnostic Interview Schedule for Children-parent version (DISC-P) and the
      Semi-structured Clinical Interview for Children and Adolescents (SCICA). Clinical
      relevance was determined using a maladjustment criterion of 61 or lower on the
      Children's Global Assessment Scale (CGAS). Pain parameters were measured with
      standardized questionnaires. Results were analysed by logistic regression.
      According to the DISC-P, 21% of the children had clinically relevant psychiatric
      disorders, predominantly anxiety disorders (18%). According to the SCICA, 28% of
      the children had clinically relevant psychiatric disorders, consisting of
      anxiety, affective, and disruptive disorders (12, 19, and 9%, respectively).
      Headache (compared to musculoskeletal pain) was an independent clinical predictor
      of psychiatric morbidity (OR = 3.10; 95% CI 1.07-8.92, p = 0.04/adjusted OR 2.99;
      95% CI 1.02-8.74, p = 0.04). In conclusion, clinically relevant psychiatric
      disorders are common among children and adolescents referred for UCP. Adding a
      child psychiatrist assessment, treatable affective and disruptive disorders
      become identifiable. Children with an additional risk are those presenting with
      headache.

PMID- 21174222
TI  - Contribution of rural-to-urban migration in the prevalence of drug resistant
      tuberculosis in China.
AB  - Increased drug resistance rates to the first-line anti-tuberculosis drugs and
      multidrug resistance (MDR) were observed in China. The objectives of this study
      were to determine the prevalence and risk factors for drug-resistant tuberculosis
      (TB) in urban China and, more specifically, to determine the contribution of
      migration to case burden and drug resistance rates of urban cities. A facility
      based epidemiological study of all active TB patients reported in the four
      districts of Shanghai and Ningbo between April 1, 2008 and March 31, 2009 was
      conducted. Residents had significantly higher drug-resistance rates than migrants
      (any drug resistance: 29.8% vs. 23.5%, respectively, P = 0.038; MDR: 10.9% vs.
      6.1%, P = 0.048). Previously treated migrant patients were more likely to harbor
      drug-resistant TB and MDR-TB than new migrant cases, with adjusted odds ratios of
      3.85 and 6.52, respectively. In total, 46.2% of the previously treated cases were
      resistant to INH, 38.5% to SM, 33.3% to RMP and 30.8% to EMB, while 13.1%, 17.5%,
      7.0% and 6.8% of new cases were resistant to the four agents, respectively. To
      prevent the transmission of drug-resistant TB among migrants and residents,
      improved case management and appropriate treatment regimens should be sustained
      to prevent acquired drug resistance.

PMID- 21174223
TI  - Zoonotic emerging infectious disease in selected countries in Southeast Asia:
      insights from ecohealth.
AB  - Most emerging diseases of humans originate in animals, and zoonotic emerging
      infectious diseases (EIDs) threaten human, animal, and environment health. We
      report on a scoping study to assess actors, linkages, priorities, and needs
      related to management of these diseases from the perspective of key stakeholders
      in three countries in Southeast Asia. A comprehensive interview guide was
      developed and in-depth interviews completed with 21 key stakeholders in Vietnam,
      Lao People's Democratic Republic, and Cambodia. We found numerous relevant actors
      with a predominance of public sector and medical disciplines. More capacity
      weaknesses than strengths were reported, with risk analysis and research skills
      most lacking. Social network analysis of information flows showed policy-makers
      were regarded as mainly information recipients, research institutes as more
      information providers, and universities as both. Veterinary and livestock
      disciplines emerged as an important "boundary-spanning" organization with
      linkages to both human health and rural development. Avian influenza was regarded
      as the most important zoonotic EID, perhaps reflecting the priority-setting
      influence of actors outside the region. Stakeholders reported a high awareness of
      the ecological and socioeconomic drivers of disease emergence and a demand for
      disease prioritization, epidemiological skills, and economic and qualitative
      studies. Evaluated from an ecohealth perspective, human health is weakly
      integrated with socioeconomics, linkages to policy are stronger than to
      communities, participation occurs mainly at lower levels, and equity
      considerations are not fully considered. However, stakeholders have awareness of
      ecological and social determinants of health, and a basis exists on which
      transdisciplinarity, equity, and participation can be strengthened.

PMID- 21174224
TI  - A phase II study of 2-methoxyestradiol nanocrystal colloidal dispersion alone and
      in combination with sunitinib malate in patients with metastatic renal cell
      carcinoma progressing on sunitinib malate.
AB  - BACKGROUND: Current treatment for metastatic renal cell cancer with vascular
      endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI) have provided
      improved overall survival, but complete responses are rare. We conducted a
      multicenter phase II study to evaluate the objective response rate of 2
      methoxyestradiol (2ME2 NCD) alone and in combination with sunitinib for patients
      with metastatic renal cell carcinoma who have progressed on sunitinib alone.
      METHODS: Adults with metastatic kidney cancer were stratified depending on
      whether they were still taking sunitinib or had discontinued sunitinib therapy at
      the time of registration. Patients were treated with 2ME2 NCD alone or in
      combination with sunitinib. The primary endpoint was objective response rate.
      RESULTS: In total, 17 patients were enrolled, and 12 were evaluable for response
      (arm A, n = 7; arm b, n = 5). In arm A, four patients had the best response of
      stable disease, and three patients developed disease progression. In arm B, three
      patients had a best response of stable disease, and two patients had disease
      progression. One patient continued to receive treatment for a total of 14 cycles
      before developing disease progression. Fatigue was the most common observed
      toxicities. Thirty five percent of patients required discontinuation of therapy
      secondary to toxicities. CONCLUSIONS: 2ME2 NCD had minimal anti-tumor activity,
      with no observed objective responses. The study was terminated because 2ME2 NCD
      was not found to be tolerable at the recommended phase 2 dose in this patient
      population. A newer 2ME2 analog is in development with a more favorable toxicity
      profile and increased potency.

PMID- 21174225
TI  - Phase II study of combination chemotherapy with biweekly cetuximab and irinotecan
      for wild-type KRAS metastatic colorectal cancer refractory to irinotecan,
      oxaliplatin, and fluoropyrimidines.
AB  - The aim of this study is to prospectively evaluate the efficacy of combination
      chemotherapy with every second week cetuximab and irinotecan in patients with
      pretreated metastatic colorectal cancer harboring wild-type KRAS. Patients with
      wild-type KRAS metastatic colorectal cancer that had progressed after
      chemotherapy with irinotecan, oxaliplatin, and fluoropyrimidine were included.
      Cetuximab was administered at 500 mg/m(2) biweekly with irinotecan. The primary
      endpoint was response rate. The pharmacokinetics of cetuximab was also evaluated
      in 5 patients. From May 2009 to February 2010, a total of 31 patients were
      enrolled from five institutions. One patient was not eligible. Among the 30
      patients who were treated with biweekly cetuximab plus irinotecan, partial
      response was observed in 9 patients. The objective response rate was 30.0% (95%
      confidence interval [CI], 14.7%-49.4%) and the disease control rate (complete
      response, partial response, or stable disease) was 76.7% (95% CI, 57.7%-90.0%).
      The median progression-free survival was 5.3 months and median overall survival
      was 10.8 months. Grade 3 skin toxicity was observed in 3 patients (10.0%) and one
      treatment related death due to pneumonia was observed. Combination chemotherapy
      with biweekly cetuximab and irinotecan was effective for pretreated metastatic
      colorectal cancer with wild-type KRAS.

PMID- 21174226
TI  - A neural network-based analysis of acoustic courtship signals and female
      responses in Chorthippus biguttulus grasshoppers.
AB  - In many animal species, male acoustic courtship signals are evaluated by females
      for mate choice. At the behavioural level, this phenomenon has been well studied.
      However, although several song characteristics have been determined to affect the
      attractiveness of a given song, the mechanisms of the evaluation process remain
      largely unclear. Here, we present a simple neural network model for analysing and
      evaluating courtship songs of Chorthippus biguttulus males in real-time. The
      model achieves a high predictive power of the attractiveness of artificial songs
      as assigned by real Chorthippus biguttulus females: about 87% of the variance can
      be explained. It also allows us to determine the relative contribution of
      different song characteristics to overall attractiveness and how each of the song
      components influences female responsiveness. In general, the obtained results
      closely match those of empirical studies. Therefore, our model may be used to
      obtain a first estimate of male song attractiveness and may thus complement
      actual testing of female responsiveness in the laboratory. In addition, the model
      allows including and testing novel song parameters to generate new hypotheses for
      further experimental studies. The supplemental material of this article contains
      the article's data in an active, re-usable format.

PMID- 21174228
TI  - Assessment of the economic viability of goat management systems in Goma Sub
      County and Mukono Town Council in Mukono District, Uganda.
AB  - This study sought to assess the profitability of the goat enterprises under
      different management systems. The research covered two selected sub-counties of
      Mukono District (Goma and Mukono Town Council). A total of 888 goats from 129
      herds/farms were studied. Descriptive statistical and gross margins analyses were
      performed. The management system of goats in the two sub-counties was mainly by
      tethering. Most of the goats kept were adult female goats. Most farmers had small
      herds and did not keep records. Male goats were more valued on average among the
      crossbred goats. In the exotic types, the adult female goats were valued on
      average. Local goats fetch low prices. With respect to gross margins, that free
      range had incurred more losses, while tethering made most profits followed by
      zero grazing and zero grazing combined with tethering, respectively, without
      considering the non-monetary aspects. Farmers using the tethering management
      system, encountered most of the problems of lack of pastures and veterinary
      services. The farmers required assistance from different donors, through
      provision of hybrid goats and improvement of veterinary services. The management
      system for goat keeping in the study area was poor, especially among local breed
      goat farmers who use tethering management system, though it had high gross
      margin. There is a need to educate farmers on proper goat husbandry and provision
      of some farm inputs.

PMID- 21174227
TI  - Control of neural synchrony using channelrhodopsin-2: a computational study.
AB  - In this paper, we present an optical stimulation based approach to induce 1:1 in
      phase synchrony in a network of coupled interneurons wherein each interneuron
      expresses the light sensitive protein channelrhodopsin-2 (ChR2). We begin with a
      transition rate model for the channel kinetics of ChR2 in response to light
      stimulation. We then define "functional optical time response curve (fOTRC)" as a
      measure of the response of a periodically firing interneuron (transfected with
      ChR2 ion channel) to a periodic light pulse stimulation. We specifically consider
      the case of unidirectionally coupled (UCI) network and propose an open loop
      control architecture that uses light as an actuation signal to induce 1:1 in
      phase synchrony in the UCI network. Using general properties of the spike time
      response curves (STRCs) for Type-1 neuron model (Ermentrout, Neural Comput 8:979
      1001, 1996) and fOTRC, we estimate the (open loop) optimal actuation signal
      parameters required to induce 1:1 in-phase synchrony. We then propose a closed
      loop controller architecture and a controller algorithm to robustly sustain
      stable 1:1 in-phase synchrony in the presence of unknown deviations in the
      network parameters. Finally, we test the performance of this closed-loop
      controller in a network of mutually coupled (MCI) interneurons.

PMID- 21174229
TI  - The development of a model for artificial insemination by backyard pig farmers in
      Thailand.
AB  - The aim of this study was to develop and evaluate a model of artificial
      insemination (AI) technology transferable to backyard pig farmers for
      strengthening pig productivity in rural areas in Thailand. An AI center, criteria
      and process for farmer selection, an AI training program, AI practice in pigs,
      and a backyard farmer network were created as a model. Five hundred and thirty
      one farrowing records from 307 sows were analyzed. Farrowing rates (FR), total
      number of piglets born (TB), and number of piglets born alive (BA) were studied.
      AI has led to better results in FR, TB, and BA than natural mating (P < 0.05).
      Demographic factors such as sex and age of farmers only had significant effects
      on FR (P < 0.05), while educational levels and farmers' AI experience had
      significant effects on TB and BA (P < 0.05). Model factors such as type of
      training, semen delivery systems, and semen storage time did not have significant
      effects on FR, TB, and BA. In conclusion, using this model, we found that
      backyard farmers could be trained in AI techniques in order to achieve equally
      good results as experienced technicians. Male farmers within working age or
      older, with a high school education or higher are the recommended target groups
      for implementing this model. Strong cooperation with clear responsibilities of
      all stakeholders could create a good network of backyard pig farmers. Therefore,
      the implementation of AI techniques in pig production can be applied to the
      target group with an aim towards a sustainable, self-sufficient community.

PMID- 21174230
TI  - A model of NMDA receptor control of F-actin treadmilling in synaptic spines and
      their growth.
AB  - Synaptic spines grow as a consequence of the formation of F-actin filaments at
      the spine head. The dynamics of F-actin in the spine head upon excitation of N
      methy-D-aspartate (NMDA) receptors has recently been investigated experimentally,
      but there is no quantitative account of how these dynamic changes occur upon
      activation of these receptors; this we now supply. Dynamics of F-actin at the
      apex of lamellipodia have been investigated in detail, giving rise to the
      treadmilling theory of F-actin dynamics, involving catalysis by profilin, for
      which quantitative models are now available. Here, we adapt such a model to
      describe the dynamics of F-actin in the synaptic-spine head and show that it
      gives quantitative descriptions of this treadmilling phenomena which are well
      fitted by Monte Carlo simulations. Next, the means by which excitation of NMDA
      receptors enhances the activity of profilin through activity of the Rho small
      GTPase RhoA and the specific kinase ROCK is discussed. This is then used to model
      the NMDA receptor excitatory enhancement of profilin and so the treadmilling
      process of F-actin dynamics in spine growth. Such modelling provides a
      quantitative description of the synaptic-spine dynamics of the filamentous to
      globular actin ratio that is observed experimentally.

PMID- 21174231
TI  - Enumeration of viral capsid assembly pathways: tree orbits under permutation
      group action.
AB  - This paper uses combinatorics and group theory to answer questions about the
      assembly of icosahedral viral shells. Although the geometric structure of the
      capsid (shell) is fairly well understood in terms of its constituent subunits,
      the assembly process is not. For the purpose of this paper, the capsid is modeled
      by a polyhedron whose facets represent the monomers. The assembly process is
      modeled by a rooted tree, the leaves representing the facets of the polyhedron,
      the root representing the assembled polyhedron, and the internal vertices
      representing intermediate stages of assembly (subsets of facets). Besides its
      virological motivation, the enumeration of orbits of trees under the action of a
      finite group is of independent mathematical interest. If G is a finite group
      acting on a finite set X, then there is a natural induced action of G on the set
      T(x) of trees whose leaves are bijectively labeled by the elements of X. If G
      acts simply on X, then |X|:=|X(n)|=n.|G|, where n is the number of G-orbits in X.
      The basic combinatorial results in this paper are (1) a formula for the number of
      orbits of each size in the action of G on T(x)(n), for every n, and (2) a simple
      algorithm to find the stabilizer of a tree tau ?T(x) in G that runs in linear
      time and does not need memory in addition to its input tree. These results help
      to clarify the effect of symmetry on the probability and number of assembly
      pathways for icosahedral viral capsids, and more generally for any finite,
      symmetric macromolecular assembly.

PMID- 21174232
TI  - Variation in lymph node assessment after colon cancer resection: patient,
      surgeon, pathologist, or hospital?
AB  - BACKGROUND: Evaluation of >= 12 lymph nodes after colon cancer resection has been
      adopted as a hospital quality measure, but compliance varies considerably. We
      sought to quantify relative proportions of the variation in lymph node assessment
      after colon cancer resection occurring at the patient, surgeon, pathologist, and
      hospital levels. METHODS: The 1998-2005 Surveillance, Epidemiology, and End
      Results-Medicare database was used to identify 27,101 patients aged 65 years and
      older with Medicare parts A and B coverage undergoing colon cancer resection.
      Multilevel logistic regression was used to model lymph node evaluation as a
      binary variable (>= 12 versus <12) while explicitly accounting for clustering of
      outcomes. RESULTS: Patients were treated by 4,180 distinct surgeons and 2,656
      distinct pathologists at 1,113 distinct hospitals. The overall rate of 12-lymph
      node (12-LN) evaluation was 48%, with a median of 11 nodes examined per patient,
      and 33% demonstrated lymph node metastasis on pathological examination.
      Demographic and tumor-related characteristics such as age, gender, tumor grade,
      and location each demonstrated significant effects on rate of 12-LN assessment
      (all P < 0.05). The majority of the variation in 12-LN assessment was related to
      non-modifiable patient-specific factors (79%). After accounting for all
      explanatory variables in the full model, 8.2% of the residual provider-level
      variation was attributable to the surgeon, 19% to the pathologist, and 73% to the
      hospital. CONCLUSION: Compliance with the 12-LN standard is poor. Variation
      between hospitals is larger than that between pathologists or surgeons. However,
      patient-to-patient variation is the largest determinant of 12-LN evaluation.

PMID- 21174233
TI  - Self-replication: spelling it out in a chemical background.
AB  - Self-replication, an important concept abstracted from reproduction, the key
      feature of life, remains vague in definition and lacking in clear interpretation
      in terms of its chemical mechanism. Mentioned frequently in discussions
      concerning the essence of life and its origin, the vague concept has caused a lot
      of uncertain statements, confusable references, and malposed debates, and has
      seriously held back efforts in this field. In this article, we try to improve the
      situation by a conceptual analysis in a more fundamental and clearer background.
      Self-replication in the substantial world could not mean anything but that "an
      entity favors the production of its own." The major chemical mechanism for such
      favoring is catalysis, which can be classified into speed- and direction-favoring
      types (the template-directing function is actually a type of direction-favoring
      catalysis). Molecular self-replication could be based on autocatalysis or self
      metabolism; the self-replication of a complex entity could be based on
      autocatalytic and/or self-metabolic sets, and should involve a mechanism of self
      division. This conceptual clarification sheds light on the dim areas concerning
      the essence of life and its origin.

PMID- 21174234
TI  - Therapeutic implications of a barrier-based pathogenesis of atopic dermatitis.
AB  - Excessive Th2 cell signaling and IgE production play key roles in the
      pathogenesis of atopic dermatitis (AD). Yet, recent information suggests that the
      inflammation in AD instead is initiated by inherited insults to the barrier,
      including a strong association between mutations in FILAGGRIN and SPINK5 in
      Netherton syndrome, the latter of which provides an important clue that AD is
      provoked by excess serine protease activity. But acquired stressors to the
      barrier may also be required to initiate inflammation in AD, and in addition,
      microbial colonization by Staphylococcus aureus both amplifies inflammation, but
      also further stresses the barrier in AD. Therapeutic implications of these
      insights are as follows: While current therapy has been largely directed toward
      ameliorating Th2-mediated inflammation and/or pruritus, these therapies are
      fraught with short-term and potential long-term risks. In contrast, "barrier
      repair" therapy, with a ceramide-dominant triple-lipid mixture of stratum corneum
      lipids, is more logical, of proven efficacy, and it provides a far-improved
      safety profile.

PMID- 21174235
TI  - Cutting edge issues in autoimmune gastritis.
AB  - Autoimmune gastritis is the outcome of a pathological CD4 T cell-mediated
      autoimmune response directed against the gastric H/K-ATPase. Silent initially,
      the gastric lesion becomes manifest in humans by the development of megaloblastic
      pernicious anemia arising from vitamin B12 deficiency. Cutting edge issues in
      this disease relate to its epidemiology, immunogenetics, a role for Helicobacter
      pylori as an infective trigger through molecular mimicry, its immunopathogenesis,
      associated organ-specific autoimmune diseases, laboratory diagnosis, and
      approaches to curative therapy.

PMID- 21174236
TI  - [Epidemiological surveillance of leptospirosis on Reunion Island in 2004-2008:
      possible impact of Chikungunya infection on the case fatality rate of
      leptospirosis].
AB  - In 2006, increased mortality due to leptospirosis in Reunion Island had alerted
      the authorities and justified the conduct of this study in order to update
      knowledge on the epidemiology of leptospirosis, whereas the latest
      epidemiological data published on the disease dated back to 2003. This study
      followed the scheme of a descriptive retrospective survey based on data from
      reporting and investigation of hospitalized cases of leptospirosis that occurred
      in Reunion between the 1st January 2004 and 31st December 2008. Data from the
      National Reference Center (NRC) have also been used. The annual number of
      reported cases (40 to 50) was stable over the period, which contrasted with the
      historical decreasing trend of incidence reported by the NRC. The circumstances
      of exposure were those usually associated with the disease on the island: about
      80% of cases were infected between January and June, during the wet season; the
      main exposure factor identified was the practice of agriculture, declared or not;
      Leptospira icterohaemorrhagiae remained the most frequently isolated serovar,
      although regressing. Finally, our study has shown that excess mortality observed
      in 2006 did not result from an increased incidence but from a rise in the case
      fatality rate. This could be linked to the outbreak of chikungunya, which peaked
      in February 2006. In endemic areas of leptospirosis, health professionals should
      remain aware of the risk of occurrence of fatal cases during arbovirosis
      outbreaks.

PMID- 21174237
TI  - [Listeriosis in Tunis: seven cases reports].
AB  - Listeria monocytogenesis a Gram positive facultative intracellular bacterium that
      can be responsible for severe infections, affecting essentially pregnant women,
      immunocompromised patients at the early and later stages of life. In Tunisia,
      invasive L. monocytogenes infections are thought to be exceptional and limited
      data are available about listeriosis. We reported seven cases (five newborn
      children and two infants) of human listeriosis that occurred in Tunis from 2000
      to 2008. The newborn children were hospitalized for suspicion of maternofoetal
      infections. The two infants were hospitalized for fever associated with digestive
      signs in one case and neurological signs in the other. L. monocytogenes-was
      isolated from culture of cerebrospinal fluid in four cases, peripheral samples in
      two cases and from blood culture in one case. Isolates identification was based
      on conventional methods. Antimicrobial susceptibility was realized according to
      the recommendation of the "Comite de l'antibiogramme de la Societe francaise de
      microbiologie". All L. monocytogenes isolates were sensitive to amoxicillin and
      aminoside but resistant to 3rd generation cephalosporins. Investigations of the
      immune system were realized for the two infants including phenotypic analysis of
      peripheral blood cells by flow cytometry, lymphocyte proliferation assays,
      phagocytic cell functions and measurement of immunoglobulins as well as
      complement. All these explorations were normal for both infants. The outcome was
      fatal in only one case (a newborn child), and all the other patients recovered
      after adapted antibiotic treatment. In conclusion, our study shows that
      listeriosis is not exceptional in Tunis. Thus, it is necessary to know how to
      evoke this diagnosis, at any age, in order to establish an early and adapted
      antibiotic treatment and to avoid fatal outcome.

PMID- 21174238
TI  - [Contribution to the establishment of quality assurance in five medical
      microbiology departments in Togo].
AB  - In Togo, as in many other developing countries, there is a lack of data on
      quality control and assurance of laboratories. The present study aimed to access
      for the quality management system in five medical bacteriology laboratories in
      Togo. The study was conducted from May to August 2006. Data were recorded by an
      audit on the reliability of results and the technical organization of
      laboratories. The standard ISO 15189:2003, the Togolese guide of good laboratory
      practices (GBEA-Togo) and the WHO medical bacteriology standards were used as
      references. The results of the audit showed a lack of culture media in
      laboratories, inappropriate choice of culture media, partial identification of
      some microorganisms, variability of identification procedures, a lack of
      diagnostic reagents and an inability to identify some potentially pathogenic
      bacteria. Concerning the technical organization of laboratories, compliance
      average ranging from 25.8 to 54.8 % was recorded. This indicates a limited
      organization of such laboratories. The issue of this study showed that
      laboratories must be equipped, their technical organization should be improved
      and they must establish a program of equipment maintenance.

PMID- 21174239
TI  - [Prevalence of child and teenage obesity in schools in Dakar].
AB  - Obesity is currently viewed as a serious worldwide public health issue. In this
      survey, we aim to determine its prevalence among schoolchildren and teenagers in
      Dakar. The sample of our survey consisted of 2,356 students aged 11-17, including
      1,110 boys and 1,246 girls. For each of them, we have calculated their body mass
      index. Based on the higher value of the norm of that index, referred to the 97th
      percentile of Rolland-Cachera MF's curves, we have identified obese students
      according to their age and sex. The prevalence of obesity within our sample is
      9.34%, with 2.88% for boys and 6.46% for girls. It is at its peak in the age of
      11, though there is no significance (p > 0.05) in its decrease (from age 12 to
      17). There are significantly (p < 0.05) more obese students in "catholic private"
      schools than in "public" schools where schooling is free. Child and teenage
      obesity is a reality in Dakar schools. Consequently, it is advisable to determine
      its nationwide prevalence to take on its prevention as well as its cure.

PMID- 21174241
TI  - Five Challenges Facing the US Physician Workforce (And What to Do About Them).
AB  - This article outlines 5 major challenges facing the US physician workforce that
      are especially important in the context of health care reform but have not been
      featured in the reform debate. Without assuring that sufficient numbers of the
      right types of physicians are available, reform efforts may not result in
      increased access to health care. Policy options for addressing these challenges
      are an important national priority in the context of effective reform of the US
      health care system.

PMID- 21174242
TI  - ACO Frenzy.

PMID- 21174243
TI  - Making health insurers insure.
AB  - A section of the Patient Protection and Affordable Care Act requires health plans
      to maintain a minimum "medical loss ratio," or MLR, of between 80 percent and 85
      percent. If they don't, they could be ordered to refund some premium dollars to
      their beneficiaries. Texas Medical Association officials say the new MLR
      provision could force health plans to spend more time providing insurance and
      less time meddling in patient care. But that is still unclear.

PMID- 21174244
TI  - Repairing the impaired.
AB  - The Texas Physician Health Program helps impaired physicians, physician
      assistants, acupuncturists, and surgical assistants get treatment for their
      problems through a monitored recovery program. The program accepts self-referrals
      or referrals from an individual, a physician health and rehabilitation committee,
      a physician assistant organization, a state physician health program, a state
      acupuncture program, any hospital or hospital system licensed in Texas, a
      residency program, the Texas Medical Board, the physician assistant board, or the
      acupuncture board.

PMID- 21174245
TI  - Acing the test.
AB  - With substantial class size increases at Texas medical schools over the past
      several years and the opening of the Texas Tech University Paul L. Foster School
      of Medicine in El Paso, there was uncertainty among many medical educators about
      whether the overall qualifications of some medical school applicants might drop.
      But, according to data released by the Texas Medical and Dental Schools
      Application Service, grade point averages and scores on the Medical College
      Admission Test for medical school applicants and first-year enrollees have been
      trending upward since 2000.

PMID- 21174246
TI  - Master of engineering program in biomedical engineering at Cornell University:
      Collaboration with external sponsors to prove concepts in assistive devices.

PMID- 21174247
TI  - Smart Walker: A tool for promoting mobility in elderly adults.

PMID- 21174240
TI  - HIV-associated neurocognitive disorders before and during the era of combination
      antiretroviral therapy: differences in rates, nature, and predictors.
AB  - Combination antiretroviral therapy (CART) has greatly reduced medical morbidity
      and mortality with HIV infection, but high rates of HIV-associated neurocognitive
      disorders (HAND) continue to be reported. Because large HIV-infected (HIV+) and
      uninfected (HIV-) groups have not been studied with similar methods in the pre
      CART and CART eras, it is unclear whether CART has changed the prevalence,
      nature, and clinical correlates of HAND. We used comparable methods of subject
      screening and assessments to classify neurocognitive impairment (NCI) in large
      groups of HIV + and HIV - participants from the pre-CART era (1988-1995; N = 857)
      and CART era (2000-2007; N = 937). Impairment rate increased with successive
      disease stages (CDC stages A, B, and C) in both eras: 25%, 42%, and 52% in pre
      CART era and 36%, 40%, and 45% in CART era. In the medically asymptomatic stage
      (CDC-A), NCI was significantly more common in the CART era. Low nadir CD4
      predicted NCI in both eras, whereas degree of current immunosuppression,
      estimated duration of infection, and viral suppression in CSF (on treatment) were
      related to impairment only pre-CART. Pattern of NCI also differed: pre-CART had
      more impairment in motor skills, cognitive speed, and verbal fluency, whereas
      CART era involved more memory (learning) and executive function impairment. High
      rates of mild NCI persist at all stages of HIV infection, despite improved viral
      suppression and immune reconstitution with CART. The consistent association of
      NCI with nadir CD4 across eras suggests that earlier treatment to prevent severe
      immunosuppression may also help prevent HAND. Clinical trials targeting HAND
      prevention should specifically examine timing of ART initiation.

PMID- 21174248
TI  - Identification of domains and measures for assessment battery to examine well
      being of spouses of OIF/OEF veterans with PTSD.
AB  - Family members play an important role in the physical and mental recovery of
      soldiers returning from Operation Iraqi Freedom (OIF) and Operation Enduring
      Freedom (OEF). Posttraumatic stress disorder (PTSD) has been associated with
      strained marital and family relations and parenting difficulties, and many
      veterans with PTSD experience difficulty finding and maintaining employment.
      Family members who assist with the veteran's recovery also experience significant
      strain and may have to leave employment to care for the veteran. Our objective
      was to identify appropriate assessment measures for examining the well-being of
      spouses assisting with veterans' recovery and to identify opportunities for
      supporting veterans' spouses. We used a combination of expert panel input and
      qualitative methods (focus group interviews) to develop a battery of instruments
      for use in future research with OIF/OEF family members to examine well-being.
      Research is needed to elucidate and refine the special needs and issues
      surrounding PTSD in current and future OIF/OEF veterans and their families. This
      study provides a first step toward understanding appropriate measures. Expert
      panel methods and focus group interviews yielded valuable input on the domains
      and measures that should be included in the assessment battery as well as
      opportunities for assisting spouses.

PMID- 21174249
TI  - Executive clock drawing correlates with performance-based functional status in
      people with combat-related mild traumatic brain injury and comorbid posttraumatic
      stress disorder.
AB  - Executive Clock Drawing Tasks (CLOX parts 1 and 2) can predict functional
      impairment. This study determined the correlation between CLOX and other
      psychometric screening instruments with the Structured Assessment of Independent
      Living Skills (SAILS)-defined performance-based functional status in people with
      combat-related mild traumatic brain injury (TBI) and comorbid posttraumatic
      stress disorder (PTSD). We hypothesized that CLOX would correlate significantly
      with functional performance. This prospective, cross-sectional study design
      determined the correlation between a structured neuropsychological battery and
      functional status assessment. We calculated Pearson correlation coefficients
      between neuropsychological instruments and functional status scores. We entered
      neuropsychological measures correlating p < 0.1 with functional status into a
      linear regression model to determine independent contributions. Fifteen Operation
      Iraqi Freedom veterans participated. Only CLOX1 correlated significantly with
      functional competency and efficiency. Only mean CLOX1 scores were significantly
      lower in those scoring below the median for SAILS competency and in those scoring
      above the median for SAILS efficiency. CLOX1 contributed significant variance to
      functional status independent of mood or anxiety symptoms and was not affected by
      age or time since injury. Executive dysfunction per the brief, easily
      administered CLOX1 is sensitive to functional status following combat-related
      mild TBI, independent of PTSD anxiety with or without depression.

PMID- 21174250
TI  - Comparison of amounts and types of practice during rehabilitation for traumatic
      brain injury and stroke.
AB  - Patients with acquired neurological deficits may capitalize on cortical
      reorganization to recover functional skills that have been lost. Research in
      neuroplasticity proposes that a high number of repetitions may lead to cortical
      reorganization. The purposes of this study were to quantify the number and type
      of activities performed by patients with traumatic brain injury (TBI) and stroke
      in physical and occupational therapy sessions to determine whether (1) the number
      of repetitions approaches the numbers in neuroplasticity research, (2) there were
      differences based on patient diagnosis, and (3) patient or therapist
      characteristics affected the type or amount of activities performed. Forty-eight
      patient and forty provider subjects participated. One hundred seven therapy
      sessions were observed. Data from therapy sessions were counted and categorized.
      Neither patient group approached the total number of repetitions neuroplasticity
      research suggests may be required for neuroplastic change. Repetitions per
      session did not differ between groups. Subjects with TBI performed more
      repetitions per minute in three categories (total upper-limb repetitions, gait
      steps, and transfers) than subjects with stroke. Therapists with <1 year or >15
      years of neurological therapy experience instructed patients in fewer functional
      repetitions per minute than did therapists with 5 to 15 years of experience.

PMID- 21174252
TI  - Evaluation of semiautonomous navigation assistance system for power wheelchairs
      with blindfolded nondisabled individuals.
AB  - Some individuals with disabilities are denied powered mobility because they lack
      the visual, motor, and/or cognitive skills required to safely operate a power
      wheelchair. The Drive-Safe System (DSS) is an add-on, distributed, shared-control
      navigation assistance system for power wheelchairs intended to provide safe and
      independent mobility to such individuals. The DSS is a human-machine system in
      which the user is responsible for high-level control of the wheelchair, such as
      choosing the destination, path planning, and basic navigation actions, while the
      DSS overrides unsafe maneuvers through autonomous collision avoidance, wall
      following, and door crossing. In this project, the DSS was clinically evaluated
      in a controlled laboratory with blindfolded, nondisabled individuals. Further,
      these individuals' performance with the DSS was compared with standard cane use
      for navigation assistance by people with visual impairments. Results indicate
      that compared with a cane, the DSS significantly reduced the number of
      collisions. Users rated the DSS favorably even though they took longer to
      navigate the same obstacle course than they would have using a standard long
      cane. Participants experienced less physical demand, effort, and frustration when
      using the DSS as compared with a cane. These findings suggest that the DSS can be
      a viable powered mobility solution for wheelchair users with visual impairments.

PMID- 21174251
TI  - Symptom burden in individuals with cerebral palsy.
AB  - The current study sought to (1) determine the relative frequency and severity of
      eight symptoms in adults with cerebral palsy (CP), (2) examine the perceived
      course of these eight symptoms over time, and (3) determine the associations
      between the severity of these symptoms and psychosocial functioning. Eighty-three
      adults with CP completed a measure assessing the frequency, severity, and
      perceived course of eight symptoms (pain, weakness, fatigue, imbalance, numbness,
      memory loss, vision loss, and shortness of breath). Respondents also completed
      measures of community integration and psychological functioning. The results
      indicated that pain, fatigue, imbalance, and weakness were the most common and
      severe symptoms reported. All symptoms were reported to have either stayed the
      same or worsened, rather than resolved, over time. The symptoms were more closely
      related to social integration than to home integration, productive activity, or
      psychological functioning. Memory loss was a unique predictor of social
      integration in the multivariate context. This study highlighted several common
      and problematic symptoms experienced by adults with CP. Additional research is
      needed to identify the most effective treatments for those symptoms that affect
      community integration and psychological functioning as a way to improve the
      quality of life of individuals with CP.

PMID- 21174253
TI  - Stop of loss of cognitive performance during rehabilitation after total hip
      arthroplasty-prospective controlled study.
AB  - Prolonged hospitalization is known to be associated with a loss of cognitive
      performance. Does playing video games (VGs) developed to improve cognitive
      properties delay this loss or even lead to an increase in cognitive performance?
      We performed a 10-day longitudinal study of patients who received total hip
      arthroplasty. We compared 16 patients (6 male) aged 66 +/- 9 years (mean +/-
      standard deviation) who played Dr. Kawashima's Brain Training: How Old Is Your
      Brain? (Nintendo; Redmond, Washington) on a Nintendo DS handheld console with 16
      control patients (6 male) aged 69 +/- 14 years. We measured cognitive performance
      1 day preoperation, as well as on days 2 and 9 postoperation. With the daily
      exercise of a specific VG by the play group, the patients' fluid intelligence
      (median intelligence quotient 99-106), working memory capacity, and rate of
      information processing significantly improved over the course of 7 postoperative
      days. The cognitive performance of the control group did not increase. However,
      the memory spans of both groups did not systematically change. Exercise with VGs
      can prevent the loss of cognitive performance during prolonged hospitalization.

PMID- 21174254
TI  - Effects of prosthetic foot forefoot flexibility on gait of unilateral transtibial
      prosthesis users.
AB  - Five solid-ankle experimental prosthetic feet were used in this double-blind
      randomized crossover study to determine the effects of forefoot flexibility on
      gait of 14 unilateral transtibial prosthesis users. Flexibility in experimental
      feet was altered by changing the number of flexural hinges in their forefoot
      sections. When experimental prosthetic foot conditions were compared, measured
      prosthetic ankle dorsiflexion range of motion increased as much as 3.3 degrees 
      with increasing flexibility (p < 0.001) and the foot's anterior moment arm
      (measured as the effective foot length ratio) increased as much as 23% of the
      foot length with decreasing flexibility (p < 0.001). Subjects also showed
      increases in the difference between sound and prosthetic ankle moments as high as
      0.53 Nm/kg in late stance phase of walking as flexibility decreased (p < 0.001).
      The difference between first peaks of the vertical ground reaction forces on the
      sound and prosthetic sides increased as much as 9% of body weight when subjects
      used the foot with the greatest flexibility (p = 0.001). The results of this
      study suggest solid-ankle prosthetic foot designs with overly flexible forefoot
      sections can cause a "drop-off" effect in late stance phase and during the
      transition of loading between prosthetic and contralateral limbs.

PMID- 21174255
TI  - Measurement of craniovertebral angle with Electronic Head Posture Instrument:
      Criterion validity.
AB  - This study evaluated the criterion-related validity of the Electronic Head
      Posture Instrument (EHPI) in measuring the craniovertebral (CV) angle by
      correlating the measurements of CV angle with anterior head translation (AHT) in
      lateral cervical radiographs. It also investigated the correlation of AHT and CV
      angle with the Chinese version of the Northwick Park Questionnaire (NPQ) and
      Numeric Pain Rating Scale (NPRS). Thirty patients with diagnosis of mechanical
      neck pain for at least 3 months without referred symptoms were recruited in an
      outpatient physiotherapy clinic. The results showed that AHT measured with X-ray
      correlated negatively with CV angle measured with EHPI (r = -0.71, p < 0.001). CV
      angle also correlated negatively with NPQ (r = -0.67, p < 0.001) and NPRS (r = 
      0.70, p < 0.001), while AHT positively correlated with NPQ (r = 0.390, p = 0.033)
      and NPRS (r = 0.49, p = 0.006). We found a negative correlation between CV angle
      measured with the EHPI and AHT measured with the X-ray lateral film as well as
      with NPQ and NPRS in patients with chronic mechanical neck pain. EHPI is a valid
      tool in clinically assessing and evaluating cervical posture of patients with
      chronic mechanical neck pain.

PMID- 21174256
TI  - [CT Angiography for the pre- and postoperative evaluation of the thoracic aorta].
AB  - CT angiography is the imaging modality of choice for the pre- and postsurgical
      evaluation of patients with pathologies of the thoracic aorta. The purpose of
      this review is to familiarize the reader with the technical principle, recent
      technical developments and requirements for specific examination protocols and
      image interpretation, and to highlight common pathologies and findings.

PMID- 21174257
TI  - [Interventional radiological imaging and treatment of port catheter
      dysfunctions].
AB  - PURPOSE: To evaluate the impact of interventional radiological imaging and
      treatment of central venous port catheter complications. MATERIALS AND METHODS:
      In this retrospective analysis 429 port catheter dysfunctions were evaluated in
      393 port catheter systems for a total of 389 patients over a period of 10 years.
      The study included 193 (49.1 %) patients with radiologically implanted port
      catheter systems and 200 (50.9 %) referred patients with surgically implanted
      port systems. Port catheter dysfunctions were subdivided into early and late
      complications as well as into non-thrombotic and thrombotic events. After
      administration of contrast medium, the port system was visualized using digital
      subtraction angiography. Data were retrospectively collected from the in-house
      databases and then analyzed descriptively. RESULTS: 429 contrast media injections
      via port catheters were performed in 393 port catheter systems. There were 359
      (83.7 %) late complications and 70 (16.3 %) early complications. In 299 (69.7 %)
      cases thrombotic events occurred and 130 (30.3 %) non-thrombotic events were
      recorded. The most common reason for contrast media injection via port catheter
      system was port catheter-related thrombosis in 269 (62.7 %) cases. 70 (16.3 %)
      catheter migrations and 30 (7.0 %) fibrin sheath formations were detected. 18
      (4.2 %) port needle malfunctions could be resolved through needle exchange. All
      15 (3.5 %) catheter disconnections had to be revised in all cases. Also six port
      explantations were performed in 6 (1.4 %) catheter fractures. CONCLUSION: The
      possibilities of angiographic imaging and interventional radiological correction
      of port catheter dysfunctions must be exploited fully in order to avoid premature
      port explantation.

PMID- 21174258
TI  - Dependence of renal blood flow on renal artery stenosis measured using CT
      angiography.
AB  - PURPOSE: The present study investigates the suitability of computed tomography
      angiography (CTA) depicting the degree of renal artery stenosis for estimating
      renal blood flow (RBF) in a kidney. MATERIALS AND METHODS: We investigated renal
      artery stenosis assessment by CTA in eight adult female hybrid pigs with an
      ultrasound probe implanted at the renal vein for RBF measurement. An inflatable
      metal-free cuff was placed around the renal artery to control the RBF. The RBF
      was then reduced in four steps. For each reduced RBF value and baseline RBF, CTA
      with a reconstructed slice thickness of 0.625 mm was performed in the arterial
      phase following injection of 80 ml of nonionic intravenous contrast medium. The
      radius of the stenotic and non-stenotic renal artery segment was measured in the
      reconstructed images. RESULTS: A significant linear correlation (p < 0.0001) was
      found between the relative apparent stenosis (calculated as the ratio of the
      radii of the actual stenotic segment and a non-stenotic renal artery segment) and
      RBF. The linear regression yielded a slope of 0.57 and a y-axis of 24.1 %. A
      significant linear correlation (p < 0.0001) was also found between the relative
      true stenosis (the ratio of the radii of the actual stenotic segment and a non
      stenotic renal artery segment at baseline) and the RBF. The linear regression
      yielded a slope of 0.67 and a y-axis of 13.8 %. CONCLUSION: The results show that
      the relative stenosis apparent on CTA differs from the true degree of renal
      artery stenosis. Nevertheless, the degree of renal artery stenosis determined by
      CTA provides a reliable estimate of the resulting RBF reduction.

PMID- 21174259
TI  - [Hernia obturatoria - a rare visceral hernia].

PMID- 21174260
TI  - [Pulmonary artery cement embolism - a possible complication after kyphoplasty].

PMID- 21174261
TI  - Genetic variability in wild genotypes of Passiflora cincinnata based on RAPD
      markers.
AB  - The genetic diversity and characteristics of commercial interest of Passiflora
      species make it useful to characterize wild germplasm, because of their potential
      use for fruit, ornamental and medicinal purposes. We evaluated genetic diversity,
      using RAPD markers, of 32 genotypes of Passiflora cincinnata collected from the
      wild in the region of Vitoria da Conquista, Bahia, Brazil. Thirteen primers
      generated 95 polymorphic markers and only one monomorphic marker. The mean
      genetic distance between the genotypes estimated by the complement of the Dice
      index was 0.51 (ranging from 0.20-0.85), and genotype grouping based on the UPGMA
      algorithm showed wide variability among the genotypes. This type of information
      contributes to identification and conservation of the biodiversity of this
      species and for the identification of pairs of divergent individuals for maximum
      exploitation of existing variability.

PMID- 21174262
TI  - DNA extraction from hair shafts of wild Brazilian felids and canids.
AB  - Wild felids and canids are usually the main predators in the food chains where
      they dwell and are almost invisible to behavior and ecology researchers. Due to
      their grooming behavior, they tend to swallow shed hair, which shows up in the
      feces. DNA found in hair shafts can be used in molecular studies that can
      unravel, for instance, genetic variability, reproductive mode and family
      structure, and in some species, it is even possible to estimate migration and
      dispersion rates in given populations. First, however, DNA must be extracted from
      hair. We extracted successfully and dependably hair shaft DNA from eight wild
      Brazilian felids, ocelot, margay, oncilla, Geoffroy's cat, pampas cat,
      jaguarundi, puma, and jaguar, as well as the domestic cat and from three wild
      Brazilian canids, maned wolf, crab-eating fox, and hoary fox, as well as the
      domestic dog. Hair samples came mostly from feces collected at the Sao Paulo Zoo
      and were also gathered from non-sedated pet or from recently dead wild animals
      and were also collected from museum specimens. Fractions of hair samples were
      stained before DNA extraction, while most samples were not. Our extraction
      protocol is based on a feather DNA extraction technique, based in the
      phenol:chloroform:isoamyl alcohol general method, with proteinase K as digestive
      enzyme.

PMID- 21174263
TI  - Differences in the number of hemocytes in the snail host Biomphalaria
      tenagophila, resistant and susceptible to Schistosoma mansoni infection.
AB  - The relationships between schistosomiasis and its intermediate host, mollusks of
      the genus Biomphalaria, have been a concern for decades. It is known that the
      vector mollusk shows different susceptibility against parasite infection, whose
      occurrence depends on the interaction between the forms of trematode larvae and
      the host defense cells. These cells are called amebocytes or hemocytes and are
      responsible for the recognition of foreign bodies and for phagocytosis and
      cytotoxic reactions. The defense cells mediate the modulation of the resistant
      and susceptible phenotypes of the mollusk. Two main types of hemocytes are found
      in the Biomphalaria hemolymph: the granulocytes and the hyalinocytes. We studied
      the variation in the number (kinetics) of hemocytes for 24 h after exposing the
      parasite to genetically selected and non-selected strains of Biomphalaria
      tenagophila, susceptible or not to infection by Schistosoma mansoni. The
      differences were analyzed referred to the variations in the number of hemocytes
      in mollusks susceptible or not to infection by S. mansoni. The hemolymph of the
      selected and non-selected snails was collected, and hemocytes were counted using
      a Neubauer chamber at six designated periods: 0 h (control, non-exposed
      individuals), 2 h, 6 h, 12 h, 18 h and, 24 h after parasite exposure. Samples of
      hemolymph of five selected mollusks and five non-selected mollusks were
      separately used at each counting time. There was a significant variation in the
      number of hemocytes between the strains, which indicates that defense cells have
      different behaviors in resistant and susceptible mollusks.

PMID- 21174264
TI  - Aspiration of radiolucent dentures in facial trauma: Case report.
AB  - Foreign body aspiration is a serious problem that may lead to complications or
      even death. People who sustain major maxillofacial trauma can often damage their
      teeth or oral prostheses, and aspiration can occur. Detection of this type of
      aspiration can be difficult, especially in elderly people wearing dental
      appliances, since many dental prostheses are not radiopaque and the aspiration is
      not always recognized at the time of injury. We report a specific case of
      extensive maxillofacial trauma from a self-inflicted gunshot wound leading to
      aspiration of large, radiolucent denture fragments, delayed diagnosis, and
      complications. The possibility of denture fragment aspiration must always be part
      of the differential diagnosis in an elderly trauma patient presenting with
      dyspnea, hypoxia or, eventually, pneumonia. This is especially so when radiologic
      evaluation does not reveal a foreign body, since much dental prosthesis material
      is radiolucent. Delayed complications of radiolucent dental prosthesis aspiration
      could be avoided by the inclusion of some radiopaque material within the acrylic
      material of the prosthesis.

PMID- 21174265
TI  - Oropharyngeal plasmablastic lymphoma in a man with human immunodeficiency virus
      infection: A case report.
AB  - Oropharyngeal lymphomas are rare, typically high-grade neoplasms. We describe a
      case of plasmablastic lymphoma that originated in the oropharynx of a 40-year-old
      man who was positive for human immunodeficiency virus (HIV). The diagnosis was
      based on fine-needle aspiration cytology of the mass followed by histopathologic
      examination supplemented with immunophenotyping. The mass was excised, but the
      patient refused antiretroviral therapy, and he died within 6 months of the
      diagnosis. In HIV-positive patients, non-Hodgkin lymphomas frequently involve
      sites, including the oropharynx, that are unusual in patients without HIV.

PMID- 21174266
TI  - Cholesterol granuloma of the external ear canal: A rare presentation.
AB  - Almost all aural cholesterol granulomas develop in the mucosa of the middle ear.
      We describe the case of a 14-year-old girl who presented with an asymptomatic,
      nontender, dark-blue, cystic lesion in the posteroinferior portion of the left
      ear canal. The mass was excised via a postauricular approach. Postoperatively,
      the mass was identified as a cholesterol granuloma on pathologic examination. To
      the best of our knowledge, this is the first reported case of a human cholesterol
      granuloma limited to the external ear canal.

PMID- 21174267
TI  - Hemangioma of a posterior ethmoid sinus: Report of a rare case.
AB  - Very few cases of hemangioma of the ethmoid sinuses have been reported in the
      literature. These lesions can be difficult to diagnose in the paranasal sinuses
      because obtaining an adequate biopsy specimen can be dangerous in view of the
      potential for profuse bleeding. We report a case of a cavernous hemangioma in the
      right posterior ethmoid sinus of a 45-year-old man. The mass was excised in its
      entirety.

PMID- 21174268
TI  - Malleus head fixation.

PMID- 21174269
TI  - Pasteurella multocida epiglottitis: A review and report of a new case with
      associated chronic lymphocytic leukemia.
AB  - Pasteurella multocida is a gram-negative coccobacillus that primarily affects
      animals. P multocida infections in humans are usually associated with animal
      contact. To the best of our knowledge, only 7 cases of P multocida epiglottitis
      have been previously reported in the English-language literature; none of these
      cases occurred in a patient with chronic lymphocytic leukemia. We describe what
      we believe is the first reported case of P multocida epiglottitis in a patient
      with chronic lymphocytic leukemia, and we review the previous reports of this
      rare entity.

PMID- 21174270
TI  - Laryngeal alveolar rhabdomyosarcoma involving the true vocal fold in an adult:
      Case report.
AB  - Rhabdomyosarcoma of the larynx is extremely rare in adults, as only 17 well
      documented cases have been previously reported in the English-language
      literature. Of these, only 2 cases (both male) involved the alveolar subtype of
      rhabdomyosarcoma, and neither involved the true vocal folds. We report a case of
      alveolar rhabdomyosarcoma of the true vocal fold in 54-year-old woman. She was
      successfully treated with conservative surgery, radiation, and chemotherapy.
      Management of head and neck rhabdomyosarcoma has evolved from radical surgery to
      less morbid procedures supplemented with radiation and chemotherapy. However,
      because this tumor is so rare in the adult population, no adult-specific
      treatment regimen has emerged. Nevertheless, the success of treatment in the
      pediatric population supports its use in adults.

PMID- 21174271
TI  - Proton pump inhibitors: Adverse effects.

PMID- 21174272
TI  - Laryngeal keratosis with underlying invasive carcinoma.

PMID- 21174273
TI  - Endoscopic view of multiple ostia of bilateral conchae bullosa.

PMID- 21174274
TI  - Lymphoepithelial cyst of the palatine tonsil.

PMID- 21174275
TI  - Correction of delayed enophthalmos using a custom-fashioned silicone sheeting
      implant.

PMID- 21174276
TI  - Incus augmentation with glass ionomer cement in primary and revision stapes
      surgery.
AB  - In stapedotomy, augmentation of the long process of the incus is necessary when
      the structure is too short or thin or when the bone has been eroded to the point
      that it is not possible to satisfactorily attach a piston prosthesis to it. One
      substance that has been used to augment the long process is glass ionomer cement
      (GIC). GIC is a dental bone cement that is finding new uses in otologic
      procedures. We conducted a retrospective study of 10 stapedotomies (6 primary and
      4 revision cases) that included the use of GIC to augment an insufficient long
      process. In all 10 cases, surgery was successful and without complication. A
      comparison of pre- and postoperative audiometry revealed significant improvements
      in mean air-conduction threshold and air-bone gap following surgery. Our findings
      suggest that GIC is safe and effective in augmenting the long process of the
      incus during both primary and revision stapedotomy.

PMID- 21174277
TI  - Fluoroscopic localization of a retained intranasal ballistic foreign body in an
      unexpected location.
AB  - Otolaryngologists are frequently asked to evaluate impacted nasal foreign bodies
      in children. Multiple techniques have been used for the removal of these objects.
      We describe what we believe is a previously unreported mechanism of nasal foreign
      body impaction and the novel method we used to remove it. We also review the
      literature on retained ballistic nasal foreign bodies, including their management
      and complications.

PMID- 21174278
TI  - Invasive fungal rhinitis caused by Paecilomyces lilacinus infection: Report of a
      case and a novel treatment.
AB  - Invasive fungal infections of the sinonasal tract are a rare but known entity in
      immunocompromised patients. Paecilomyces lilacinus is a nematophagous fungi with
      septate hyphae that has afflicted humans in multiple forms, causing cutaneous,
      ocular, and sinonasal infections. Only 4 cases of P lilacinus and 2 cases of
      Paecilomyces variotii in the sinonasal tract have been reported in the
      literature. We present a case of invasive fungal rhinitis secondary to P
      lilacinus infection in an immunocompromised patient. She was managed successfully
      with a novel treatment: voriconazole and endonasal microdebridement.

PMID- 21174279
TI  - Malignant peripheral nerve sheath tumor of the infratemporal fossa with
      intracranial extension.
AB  - Malignant peripheral nerve sheath tumor (MPNST) is an uncommon neoplasm that
      rarely involves the head and neck region. We report the case of a 66-year-old man
      who presented with symptoms compatible with uncinate seizures. Imaging studies
      detected a left infratemporal fossa tumor with bone tissue destruction and
      extension into the intracranial compartment, which exerted a mass effect on the
      temporal lobe. Histologic studies identified the tumor as an MPNST. Complete
      removal of the lesion was not possible, so the patient was treated with adjuvant
      radiotherapy. He died 6 months later. This rare case of MPNST with intracranial
      involvement illustrates the dismal prognosis for patients with such a lesion.
      Survival is limited because of the difficulty of performing radical surgery with
      free margins in such a location.

PMID- 21174280
TI  - Sclerosing mucoepidermoid carcinoma of the salivary gland: Case report and
      literature review.
AB  - Sclerosing mucoepidermoid carcinoma (SMEC) is an extremely rare variant of
      mucoepidermoid carcinoma with unique histologic features. To the best of our
      knowledge, only 14 cases of salivary gland SMEC have been previously reported in
      the English-language literature since it was discovered in 1987. We report a new
      case of salivary gland SMEC, and we review the literature. Because of SMEC's
      distinctive histologic features and rarity, its diagnosis can be difficult.
      Moreover, no clear treatment strategy has emerged with regard to adjuvant
      postoperative radiotherapy. We attempt to elucidate a natural course of this
      disease, and we propose a conservative approach to postoperative management.

PMID- 21174281
TI  - Influence of treatment strategy on serum adiponectin, resistin and angiogenin
      concentrations in patients with stable multivessel coronary artery disease after
      one-year follow-up.
AB  - BACKGROUND: Adiponectin and resistin, as well as the novel angiogenetic factor
      angiogenin, may be associated with inflammation and atherosclerosis. However, the
      available data are limited regarding adipocytokines and angiogenesis factors long
      term serum concentration changes in patients with coronary artery disease (CAD).
      AIM: To evaluate the treatment strategy-dependent changes in serum concentrations
      of adiponectin, resistin and angiogenin in patients with stable multivessel CAD
      (MCAD) and their association with cardiovascular events. METHODS: The study group
      comprised 107 MCAD patients (80 males, mean age 63+/-8 years); 55 (51%) patients
      were treated surgically (coronary artery bypass grafting-CABG), while the other
      52 (49%) were treated medically. Adiponectin, resistin and angiogenin plasma
      levels were measured on admission and after one-year follow-up. Major adverse
      cardiac events (MACE) were defined as cardiac death, non-fatal myocardial
      infarction, stroke or hospitalisation for angina or heart failure over the 12
      month period. RESULTS: During one-year follow-up, nine (8%) patients died, all
      from cardiovascular causes, and 34 (32%) patients experienced MACE. The CABG
      group revealed significant decrease in angiogenin (p<0.0001) and adiponectin
      (p=0.03) serum levels. In the medically treated group, we noted a significant
      reduction in the adiponectin serum concentration (p=0.003), with no change in
      resistin and angiogenin serum levels. CONCLUSIONS: In stable patients with MCAD,
      the choice of treatment strategy (optimal medical therapy or surgery) influences
      cytokines profile and modifies serum concentration of angiogenin and adiponectin
      during 12 months of follow-up. Assessing the dynamic concentration changes of
      these novel biomarkers may be useful for clinical practice.

PMID- 21174282
TI  - [Comment to article. Adipokiny w chorobie niedokrwiennej serca].

PMID- 21174283
TI  - Chronotropic response during exercise and recovery in men with mild systolic
      chronic heart failure.
AB  - BACKGROUND AND AIM: Pattern of heart rate (HR) changes during exercise and
      recovery is deranged in patients with cardiovascular disease, being considered as
      an independent predictor of poor outcome. This issue has been poorly examined in
      patients with chronic heart failure (CHF), particularly in the early stages of
      this syndrome. METHODS: Cardiopulmonary exercise testing (CPX) was performed in
      54 men with sinus rhythm with mild stable systolic CHF in NYHA class I-II (age
      57+/-12 years, LVEF 31+/-8%) and in 27 male volunteers without CHF (age 54+/-8
      years, LVEF 67+/-7%). Apart from peak oxygen consumption (peakVO2), chronotropic
      response was evaluated using the following parameters: peak heart rate (HR)
      expressed in absolute values (maxHR) and age-predicted maximal values (%maxHR),
      HR increase during exercise (DeltaHR), chronotropic index (CI=DeltaHR/predicted
      DeltaHR) and a regression coefficient of a linear function between HR and time
      during exercise (HR-time slope). Chronotropic response was also evaluated during
      recovery based on a regression coefficient of a linear function between HR and
      time during the first three-min of recovery (HR-time slope) and HR decrease after
      90 s (HRR90), 120 s (HRR120) and 180 s (HRR180) from peak exercise. RESULTS: Men
      with CHF in NYHA II and I class demonstrated impaired chronotropic response to
      exercise as compared to control peers: NYHA II vs NYHA I vs control: maxHR 122+/
      24 vs 154+/-25 vs 166+/-13 bpm, all p<0.05; %maxHR 76+/-14 vs 91+/-11 vs 101+/
      7%, all p<0.001; DeltaHR 48+/-20 vs 75+/-20 vs 91+/-14 bpm, all p<0.01; HR-time
      slope during exercise 5.6+/-2.2 vs 6.5+/-2.6 vs 8.3+/-1.2, all p<0.01 (NYHA I vs
      NYHA II, p>0.2); CI 0.56+/-0.36 vs 0.85+/-0.21 vs 1.02+/-0.13, all p<0.01; HR
      time slope during three-min of recovery -14.0+/-7.0 vs -19.2+/-5.1 vs -23.5+/
      3.8, p<0.05 (NYHA I vs control p>0.2); HRR90 30+/-17 vs 44+/-14 vs 49+/-9 bpm,
      p<0.05 (NYHA I vs control p>0.2); HRR120 35+/-8 vs 51+/-13 vs 59+/-9 bpm, all
      p<0.05; HRR180 41+/-17 vs 57+/-15 vs 68+/-10 bpm, all p<0.01. In CHF men,
      impaired peakVO2 was related to HR response to exercise (r=0.60, p<0.001) and
      recovery (r=0.50, p<0.001). Abnormal HR response to recovery correlated also to
      high NT-proBNP (r=0.33, p<0.05). In 13 men with CHF in whom CPX was performed
      twice between 17+/-11 days, variability coefficients for analysed parameters of
      chronotropic response ranged 8-15%. CONCLUSIONS: Parameters reflecting the
      chronotropic response to exercise and recovery are characterised by a good
      reproducibility, hence may be useful in the clinical assessment of patients with
      CHF. There is a marked reduction of chronotropic response in patients in the
      early stages of CHF, which may be another mechanism limiting exercise capacity.

PMID- 21174284
TI  - [Comment to article. Wysilek i czestotliwosc rytmu serca w CHF].

PMID- 21174286
TI  - [Comment to article. Znaczenie prewencji w redukcji zgonow wiencowych].

PMID- 21174285
TI  - The impact of the Polish national Programme of Cardiovascular Disease Prevention
      on the quality of primary cardiovascular disease prevention in clinical practice.
AB  - BACKGROUND: Despite a decline since 1991, cardiovascular diseases (CVD) are the
      major burden on public health in Poland. AIM: To assess the impact of the
      national Programme of Cardiovascular Disease Prevention (PCVDP) on the quality of
      primary CVD prevention in clinical practice. METHODS: Sixty six primary care
      centres were invited to join the project (2-6 in each province). Half of these
      centres participated in the PCVDP (in other words, they were 'active' clinics)
      and the other half was included in the control group. A random sample of 300
      patients aged 35-55, free of coronary heart disease, with no history of stroke or
      peripheral artery disease, and with medical documentation going back at least to
      1 January 2005 was selected for the study in each centre. From the total of 3,940
      patients in active clinics, 3,162 were judged to be eligible for the study and
      their medical records were reviewed. All were invited for examination. This was
      finally attended by 2,314 patients from active clinics and 2,101 from the control
      group. RESULTS: Before the introduction of the PCVDP, the percentage of patients
      with available information on risk factors in medical records was similar in the
      active and in the control clinics, and varied from more than 40% (hypertension)
      to less than 5% (weight and waist circumference). After the introduction of the
      PCVDP, the proportion of subjects with available information on risk factors
      greatly increased in the clinics which took part in the PCVDP. Knowledge of CVD
      risk factors was similar in the two studied groups. When asked, about 10% of
      patients in both groups could not list a single CVD risk factor. Smoking was the
      most frequently recognised risk factor (named by more than 60% of patients) and
      diabetes the least (less than 15%). No significant difference was found between
      the active and control clinics in the frequency of counselling as to smoking,
      diet, weight reduction or exercise. Only about 40% of smoking patients had
      received advice on smoking cessation. Counselling on diet had been received by
      about 40% of patients. Less than 20% of patients had been advised to reduce
      weight, with about 25% having received advice to increase their physical
      activity. Control of risk factors was poor and there was no significant
      difference between the active and control clinics in terms of the proportion of
      patients who reached prevention targets. CONCLUSIONS: 1. The PCVDP appears to be
      effective in identifying high risk patients. 2. The effectiveness of the routine
      management of risk factors in primary care is very low. 3. Addressing via the
      PCVDP all decisions as to the extent and means of intervention on risk factors to
      primary care physicians appears to be ineffective. 4. There is a need to
      introduce an effective structured intervention on risk factors and add it to the
      PCVDP.

PMID- 21174287
TI  - Functionally driven complete vs incomplete revascularisation in multivessel
      coronary artery disease--long-term results from a large cohort.
AB  - BACKGROUND: Complete revascularisation (CR) by means of percutaneous coronary
      intervention (PCI) has been associated with better long-term prognosis than
      incomplete revascularisation (IR) in several clinical trials. However, in the
      published studies, the completeness of myocardial revascularisation has been
      judged mainly on an anatomical basis, while including criteria directed at
      functionally driven IR might lead to different results. AIM: To examine the
      potential value of functionally driven IR in a large cohort of patients with
      multivessel coronary artery disease (MVD) undergoing PCI. METHODS: The study
      population consisted of 908 patients with MVD undergoing PCI without stenting
      between 1988 and 1997. Functionally driven IR was defined as dilation of all
      segments with >70% stenosis, with the exception of arteries supplying an area of
      previous transmural myocardial infarction (MI) or a small amount of myocardium.
      Complete revascularisation was defined as successful PCI of all coronary artery
      lesions with significant narrowing not fulfilling the above criteria. Patients
      were followed for a mean 11 years (range 8-16 years). End-points included: death,
      MI, re-PCI or coronary artery bypass grafting (CABG). RESULTS: Complete
      revascularisation was performed in 284 (31.3%) patients. Follow-up was obtained
      from 873 (96.1%) patients. There was no significant difference in the frequency
      of all-cause mortality, cardiovascular deaths or MI between patients who
      underwent CR and IR. Patients who underwent IR were more likely to require re-PCI
      and had a trend toward more frequent CABG. CONCLUSIONS: In comparison to CR, a
      strategy of functionally driven IR by means of PCI without stenting does not
      increase the rate of major cardiovascular outcomes, but is related to higher
      frequency of repeat procedures during a long-term follow-up.

PMID- 21174288
TI  - [Comment to article. Pelna rewaskularyzacja a najnowsze wytyczne].

PMID- 21174289
TI  - Aortic strain, distensibility and elastic modulus are associated with the
      presence and quantity of coronary calcium.
AB  - BACKGROUND: An association between aortic stiffness and atherosclerosis has been
      previously demonstrated by pulse wave velocity. Whether echocardiographically
      assessed aortic stiffness also correlates with the extent of atherosclerosis has
      not yet been established. AIM: To evaluate the association between
      echocardiographically measured aortic stiffness and atherosclerosis. METHODS: A
      total of 162 patients (mean age 54+/-9 years, age range 36-83 years, 102 male and
      60 female) at high risk of atherosclerosis underwent transthoracic
      echocardiography and sphygmomanometer-based brachial blood pressure measurement
      for aortic stiffness parameters (strain, distensibility and elastic modulus), and
      multidetector computed tomography for the presence and quantity of coronary
      artery calcium (CAC). RESULTS: It was found that aortic strain and distensibility
      were significantly lower in patients with CAC than in patients without CAC (7.6+/
      2.7% vs 9.3+/-3.4%, p<0.001 and 3.0+/-1.1 mm Hg(-1).10(-3) vs 3.9+/-1.7 mm Hg(
      1).10(-3), p<0.001, respectively). However, elastic modulus E(p) was
      significantly higher in patients with CAC than in patients without CAC (7.9+/-3.8
      N/m2 vs 6.0+/-2.5 N/m2, p=0.001). In addition, aortic strain and distensibility,
      and elastic modulus, were found to be significant predictors of the presence and
      quantity of CAC in multivariate logistic and linear regression analyses (all
      p<0.05). CONCLUSIONS: Echocardiographically measured aortic stiffness is
      positively, significantly and independently associated with atherosclerosis.

PMID- 21174290
TI  - [Comment to article. Odksztalcenie sciany aorty--czy wazne w chorobie
      niedokrwiennej?].

PMID- 21174291
TI  - Effect of gender on efficacy of preoperative intra-aortic balloon pump in high
      risk patients undergoing surgical coronary revascularisation.
AB  - BACKGROUND: There is no strong evidence supporting the use of preoperative intra
      aortic balloon pump (IABP) in high-risk patients undergoing coronary artery
      bypass grafting (CABG). This issue has only been investigated in small studies
      which analysed the general population of patients, without focusing on specific
      subgroups, including gender. AIM: We sought to determine if there is any benefit
      from preoperative IABP in high-risk patients undergoing CABG with the analysis of
      its determinants including gender. METHODS: We randomly assigned 502 high-risk
      patients (351 men, 151 women) to the group receiving preoperative IABP support or
      to the control group with no preoperative IABP. Primary end-point was a major
      adverse cardiac or cerebrovascular event (MACCE), defined as death from any
      cause, myocardial infarction, cerebrovascular accident or repeat
      revascularisation within 30 days post-surgery. RESULTS: A significant reduction
      of MACCE rate in patients with the preoperative IABP counterpulsation in
      comparison to controls was noticed in the total population of high risk patients
      (p=0.001) and in the female subgroup (p=0.005). After adjustment for baseline
      characteristics, the hazard ratio for MACCE was 0.7 (p=0.005) in the total
      population; 0.6 (p=0.01) for females and 0.8 (p=0.1) for males. CONCLUSIONS:
      There is a beneficial effect of preoperative IABP use in high-risk patients
      undergoing CABG, particularly in women and patients with co-morbidities
      (diabetes, obesity, and peripheral vascular disease).

PMID- 21174292
TI  - [Comment to article. Czy warto czekac z zalozeniem kontrapulsacji
      wewnatrzaortalnej u niestabilnego chorego?].

PMID- 21174293
TI  - [Right ventricular metastasis of leiomyosarcoma].
AB  - We present a case of a 57 year-old patient with a right ventricular metastasis of
      leiomyosarcoma. The patient was subjected to a tumour excision and a
      supplementary radiotherapy 12 years earlier. Non-characteristic symptoms and
      adverse medical history of coronary heart disease (three remote myocardial
      infarctions) delayed diagnosis and treatment. Because the disease was advanced,
      the patient was disqualified from surgical treatment. Good clinical condition,
      however, allowed for gemcitabine treatment, however, long-termed prognosis is
      poor.

PMID- 21174294
TI  - Severe unexplained heart failure in a young person.
AB  - Acute heart failure in previously healthy young patients is a diagnostic
      challenge. We describe a case of severe acute heart failure in a 38 year-old
      patient complicated by acute renal failure and incidental abdominal mass.

PMID- 21174295
TI  - [Complete atrioventricular block due to hyperkalemia caused by rhabdomyolysis
      during treatment with statin].
AB  - Complete atrioventricular block can occur, among others, in case of hyperkalemia,
      that is a life-threatening complication of rhabdomyolysis. Statins constitute the
      medication group that is especially associated with a possibility of muscle
      complications. Frequency of statin-associated myalgia is 5-10%, and potentially
      fatal rhabdomyolysis--0.02-0.09%. We describe a male patient who was admitted due
      to syncope caused by complete atrioventricular block. Iatrogenic rhabdomyolysis
      with life-threatening hyperkalemia, that was related to statin, was diagnosed.
      After application of suitable pharmacotherapy, conduction abnormalities resolved.
      The patient was discharged in a good condition.

PMID- 21174297
TI  - [Intraventricular septum rending from inferoposterior left ventricular wall
      during myocardial infarction].
AB  - Intraventricular septum (IVS) rending from left ventricular wall after acute
      myocardial infarction is a rare and dramatic mechanical complication. We describe
      a patient, who survived after rending of IVS from left ventricular
      inferoposterior wall after acute myocardial infarction. This complication was
      diagnosed using transthoracic and transesophageal echocardiography and confirmed
      by 64 MSCT. The patient underwent successful IVS repair plus three coronary
      artery bypass grafts and inferoposterior wall aneurysm plasty.

PMID- 21174299
TI  - [Is it possible to reduce reperfusion injury in acute myocardial infarction?].

PMID- 21174300
TI  - [Cardiac shock wave therapy--a new method for treatment of advanced coronary
      disease and refractory angina].
AB  - Despite continuous progress in pharmacological management and development of
      myocardial revascularisation techniques, a significant number of patients with
      advanced ischemic heart disease and refractory angina pectoris cannot be treated
      successfully. For the group of patients with chronic refractory angina
      therapeutic options are, however, limited. Several alternative therapies, such as
      transmyocardial laser revascularisation, transcutaneous electrical nerve
      stimulation or angiogenesis by gene or cell therapy have been clinically tested.
      This paper presents a new promising method, non-invasive cardiac shock wave
      therapy with a review of available clinical information on therapeutic potential
      in advanced ischemic heart disease and refractory angina treatment. The method is
      based on percutaneous application of low frequency ultrasound, i.e. mechanical
      shock waves with ECG gating. Therapeutic sessions are performed under
      echocardiographic monitoring. In the last thirty years the shock wave therapy has
      become a method efficiently employed in nephrology, gastroenterology,
      orthopedics, rehabilitation and dermatology, as well as--pending confirmation
      through further research--cardiology.

PMID- 21174301
TI  - [Syncope in male--let us think about Brugada syndrome! Presentation of 3 cases].
AB  - Brugada syndrome is a genetic disease characterised by ST segment elevation in
      right precordial leads and the occurrence of episodes of polymorphic ventricular
      tachycardia. It is also associated with a high risk of sudden death. We describe
      three males in whom Brugada syndrome was finally diagnosed after several
      hospitalisations due to syncope and ventricular tachycardia.

PMID- 21174303
TI  - [Metastatic malignant cardiac tumour--a case report].
AB  - We present a case of a 58 year-old patient with metastatic malignant cardiac
      tumour in whom the first manifestation of heart involvement was cardiac
      tamponade.

PMID- 21174304
TI  - Progression of a small eccentric aneurysm to spontaneous coronary dissection
      within the left main coronary artery.
AB  - A 67 year-old man presented with stable angina pectoris. He underwent primary
      angioplasty with stenting of the left anterior descending artery ostial lesion
      five months previously. A small eccentric aneurysm was shown within the left main
      coronary artery. A second angiography, performed a month later, showed slight
      enlargement of the aneurysm from the base side. In the final presentation,
      angiography revealed spontaneous dissection line beginning from the aneurysm base
      and extending to the left anterior descending artery. Although progression from
      coronary aneurysms to dissection is rare, it can occur, and patients monitored
      closely, especially when left main coronary aneurysm is present.

PMID- 21174306
TI  - [12-year follow-up of a patient after successful ablation of incessant fascicular
      tachycardia with biventricular heart failure and severe sinus node dysfunction].
AB  - We present a case of a 14 year-old boy with a incessant fascicular tachycardia
      with retrograde conduction and tachycardiomyopathy. Verapamil, adenosine,
      lignocaine and repeated cardioversions were unsuccessful in termination of
      tachycardia. Amiodarone however caused sinus node dysfunction and temporary
      electrode pacing had to be used. The patient underwent successful radiofrequency
      catheter ablation in the area of the left posterior fascicle. Because of
      ventricular extrasystoles (with QRS morphology resembling that of fascicular VT)
      the patient underwent second ablation which significantly reduced the number of
      ventricular beats. The course of subsequent 12-year follow-up was uneventful.

PMID- 21174307
TI  - [Commentary to the article: Leon MB, Smith CR, Mack M et al. Transcatheter aortic
      valve implantation for aortic stenosis in patients who cannot undergo surgery.
      NEJM, 2010; DOI: 10.1056/NEJMoa1008232].

PMID- 21174308
TI  - [Comment to article. Badanie PARTNER--pierwszy krok w kierunku powszechnego
      zastosowania przeznaczyniowej implantacji jako sposobu leczenia ciasnego zwezenia
      zastawki aortalnej?].

PMID- 21174309
TI  - [Novel approaches for treatment of atrial fibrillation--a cooperation between
      cardiologist and cardiac surgeon].

PMID- 21174310
TI  - The use of a novel type of distal protection system (FiberNet(r)) in the
      percutaneous management of saphenous vein graft disease.
AB  - Percutaneous intervention in saphenous vein grafts is associated with a high risk
      of distal embolisation by plaque material, 'no flow' phenomenon and clinical
      complications such as myocardial infarction or death. According to randomised
      trial evidence, intervention in a degenerated vein graft should be performed
      using an embolic protection device (EPD), since this strategy significantly
      reduces periprocedural and 30 day adverse event rate. FiberNet(r) is a novel
      distal protection system with unique characteristics of a low crossing profile
      (0.031'' for vessel size 3.5-5 mm), 'cotton wool'-like three dimensional design
      and a small pore size (40 MUm). The FiberNet(r) does not require a separate
      delivery sheath and self-achieves its optimal apposition to the vessel wall; the
      EPD system also contains a dedicated aspiration catheter. We present the use of
      FiberNet(r) in a 77 year-old patient who had undergone coronary artery bypass
      grafting 20 years ago and currently presented with CCS class III angina due to a
      significant stenosis of the saphenous vein graft to the marginal branch. The
      procedure involved the use of a novel mesh-covered stent (MGuard(r)) designed to
      'trap' the plaque material between the stent and the vessel wall. It was
      technically successful and clinically uncomplicated, and the patient remains well
      six months later.

PMID- 21174343
TI  - [Expression and identification of Bm-TFF2 in Pichia pastoris].
AB  - Bm-TFF2, an amphibian trefoil factor, which is isolated from skin secretions of
      frog Bombina maxima, has much stronger biological activities than human TFFs. In
      the present study, Bm-TFF2 gene was amplified by polymerase chain reaction (PCR)
      from its cDNA and cloned into Pichia pastoris expression vector pPIC9K containing
      AOX1 promoter and alpha -factor leader sequence. Multi-copies insertion
      transformants were screened on G418 plates. After the induction by 1% methanol
      for 72 hours, the expression of Bm-TFF2 came up to the best quantity which was
      about 50 mg in 1L medium, and 80% saturation ammonium sulfate was suitable to
      collect the Bm-TFF2 protein, as identified by SDS-PAGE and Western blotting
      assay. The results showed that the plasmid of Bm-TFF2-pPIC9K was constructed
      successfully and expressed abundantly in eukaryotic expression system, which lies
      basis for researching further the biological activities and the relationship of
      structure and functions of Bm-TFF2.

PMID- 21174344
TI  - Isolation and characterization of Hainantoxin-II, a new neurotoxic peptide from
      the Chinese bird spider (Haplopelma hainanum).
AB  - Hainantoxin-II (HnTx-II), a novel neurotoxin, was isolated from the venom of the
      Chinese bird spider (Haplopelma hainanum) by cation exchange chromatography and
      reverse-phase HPLC. The toxin was a single chain polypeptide with calculated
      molecular weight of 4 253.135 obtained by mass spectrometry. The complete amino
      acid sequence of HnTx-II was determined by Edman degradation and found to contain
      37 residues with three disulfide bonds. Results showed HnTx-II can reversibly
      paralyze cockroaches for several hours after intra-abdominal injection with ED50
      of 16 ug/g and kill the insects immediately at a dose of 60 ug/g. It was also
      shown to kill mice at a LD50 value of 1.41ug/g after intracerebroventricular
      injection. Hainantoxin-II shares 91% sequence homology with Huwentoxin-II (HwTx
      II), an insecticidal peptide from another bird spider (Haplopelma schmidti) with
      a unique scaffold. While HnTx-II and HwTx-II both exhibit toxic activities in
      insects and mammals, HnTx-II shows higher insecticidal activity and lower
      lethiferous activity of mammals than HwTx-II. These results help clarify
      structural-functional relationships of the polypeptide toxin.

PMID- 21174345
TI  - [Genetic characteristics on exon 4 of prolactin gene in 12 water buffalo
      populations].
AB  - The prolactin exerts obvious adjustment and control function for mammary gland
      development, lactation and milk protein gene expression in water buffalo. In this
      study the sequence features and polymorphisms of the exon 4 in prolactin gene
      were examined in 385 individuals which came from 12 river and swamp type buffalo
      populations using DNA direct sequencing and PCR-SSCP methods. The results showed
      that the sequence of exon 4 in prolactin gene was consists of 180 nucleotides,
      the fragment had high conservative character in different species. The e4. 109
      C>T substitution was detected in nine swamp buffalo populations, and it was a
      silent mutation and was not associated with the traits of milk yield in buffalo.
      The PBA gene was the predominant gene in seven swamp type buffalo populations,
      while PBB gene was the dominant gene in Dehong and Fuzhong populations. The
      frequencies of PBA in swamp type buffalo was 0.400 -0.917 and the average value
      was 0.629+/-0.049. The polymorphism wasn't found in river buffalo, all the
      samples from river buffalo were holding nucleotides e4.109 C. The results
      indicate that there is distinct genetic differentiation between swamp and river
      type buffalo.

PMID- 21174346
TI  - [Correlation and location of EST markers with cold tolerance trait of common carp
      (Cyprinus carpio L)].
AB  - Expressed sequence tags (ESTs) are parts of complementary DNAs (cDNAs) with
      certain gene function.It provides us more information than other neutral markers.
      The association of EST markers with phenotypes can increase our understanding of
      the biochemical pathways and mechanisms affecting economically important traits.
      In this study, 12 candidate EST markers isolated from the cold-induced brain cDNA
      of common carp (Cyprinus carpio L.) were conducted the correlation analysis of
      marker and cold tolerance trait of common carp using GLM model of SPSS 17.0
      software firstly, then tried to locate them in the genetic linkage map using
      OneMap software. As a result, eight out of 12 candidate EST makers were
      separately located in six linkage groups, in which marker CC009(P<0.05) and CC115
      (P<0.01) were associated with cold tolerance and mapped to LG38 and LG2,
      respectively. Homology identity alignments showed that marker CC009 was highly
      homologous to the known Uridine-cytidine kinase I of Danio rerio with an identity
      of 94%, and marker CC115 was lowly homologous to the putative glycosyl
      transferase of Prochlorococcus marinus with an identity of 56%.

PMID- 21174347
TI  - [Cloning and expression pattern analysis of a lipopolysaccharide -and beta-1,3
      glucan-binding protein in Portunus trituberculatus].
AB  - The lipopolysaccharide -and beta-1,3-glucan-binding protein (LGBP) is a pattern
      recognition receptor, which is fundamental for the innate immune response of
      crustaceans. A LGBP gene was cloned from the haemocytes of Portunus
      trituberculatus using SMART RACE methods. The full-length LGBP cDNA (1 378 bp)
      had a 1 095 bp open reading frame encoding a protein of 365 amino acid residues
      including a 16 amino acid residues signal peptide, a 138 bp 5' untranslated
      region (UTR) and a 144 bp untranslated region in the 3' UTR with a 29 bp polyA
      tail. The calculated molecular mass of the mature protein (349 amino acid
      residues) is 39,825.24 with an estimated pI of 4.49. The gene sequence and
      secondary structure of LGBP were analyzed by bio-informatics. Additionally, a
      Glyco hydro 16 domain was identified. The expression of P. trituberculatus in
      various tissues were detected through RT-PCR methods. The results showed that the
      LGBP gene expressed in all the tissues detected, including haemocytes,
      hepatopancreas, heart, gills and muscle. In response to the challenge of
      Staphyloccocus aureus and Vibrio alginolyticus, the LGBP gene expression in
      haemocytes of the group challenged with mixed bacteria were higher than the
      control group within 48 h. It suggested that the LGBP gene plays an active role
      in immunologic process against bacterial infection.

PMID- 21174348
TI  - [Molecular cloning, sequence analysis and expression pattern of hepcidin gene in
      ayu (Plecoglossus altivelis)].
AB  - Hepcidin, a member of cysteine-rich antimicrobial peptides, plays an important
      role in both fish adaptive immunity and the regulation of iron metabolism. In
      this paper, the nucleotide sequence of a full-length cDNA clone for ayu
      (Plecoglossus altivelis) hepcidin gene, 763 nucleotides in length, was
      determined. Ayu hepcidin gene contained a complete open reading frame (ORF)
      encoding an 85-amino-acid peptide with a molecular weight of 9.7 k. A signal
      peptide of 24 residues existed in hepcidin N-terminus. The ayu hepcidin mature
      peptide sequence contained 25 amino acids with eight cysteines that formed four
      disulfide bonds. Sequence comparison and phylogenetic analysis showed that ayu
      hepcidin was most similar to Atlantic salmon (Salmo salar), and the relationships
      of the different hepcidin coincided well with the evolutionary relationships of
      their organisms. In healthy ayu, hepcidin mRNA was mainly expressed in the liver,
      spleen, kidney, heart, and muscle. After Listonella anguillarum infection, liver
      hepcidin mRNA expression change was determined by quantitative real-time PCR (qRT
      PCR) method. Hepcidin transcripts of ayu liver were significantly up-regulated
      and peaked at 12 h. These results suggest that hepcidin may be involved in the
      immune response of ayu.

PMID- 21174350
TI  - [Summer habitat selection of alpine musk deer in Xinglongshan National Nature
      Reserve, Northwestern China].
AB  - During July and August from 2006 to 2008, summer habitat selection was studied in
      Alpine musk deer (Moschus sifanicus) in Xinglongshan National Natural Reserve in
      northwestern China. In total, seventy one musk deer utilized habitat plots and
      246 random habitat plots were surveyed. Seventeen habitat characteristics were
      recorded and compared between the two habitat types, using Mann-Whitney U test
      and chi-square to compare the differences between utilized and random habitat
      plots, and principal component analysis (PCA) to determine the main factors
      influencing the habitat selection of musk deer. Mann-Whitney U test and chi
      square was conducted to test whether there was significant difference between
      utilized and random plots. The results showed that musk deer prefers habitat with
      taller arbor height (7.57 +/- 0.83 ) m, higher food-plants abundance (12.97 +/-
      1.80), increasing foliage cover for concealment, lower water dispersion, and
      higher anthropogenic disturbance. Furthermore, PCA results suggested that the
      arbor characteristics (arbor canopy and arbor DBH), altitude characteristic, food
      characteristics (ground-plant cover and food-plant abundance) and shrub
      characteristics (shrub canopy, shrub height and related arbor density) influence
      summer habitat selection patterns of alpine musk deer in Xinglongshan National
      Nature Reserve. The general pattern of summer habitat utilization and selection
      of alpine musk deer is an adaptive strategy to the changing food, concealment,
      water source and the physical condition of summer habitat.

PMID- 21174349
TI  - [cDNA cloning and tissue-differential expression of Na+/K+/2Cl(-)-cotransporter 1
      alpha isoform in Sarotherodon melanotheron].
AB  - The gills are the major apparatus for osmoregulation in fish to acclimate the
      changes of salinities. Na+/K+/2Cl(-)cotransporter 1-alpha (NKCC1 alpha) is one of
      the key ion cotransporter locoalized in gill chloride cells which has been
      associated with the maintence of osmotic homeostasis. The transport process
      mediated by NKCC1 alpha is characterized by electroneutrality with a
      stoichiometry of 1Na:1K:2Cl. Sarotherodon melanotheron is one of the most
      euryhaline teleosts able to withstand variations in environmental salinity
      ranging from freshwater to hyper-saline waters. In this study, the reverse
      transcription-polymerase chain reaction and rapid amplification of 3' and 5'cDNA
      ends methods were used to identify the full cDNA of the NKCC1 alpha with an Open
      Reading Frame which contains 1 151aa of S.melanotheron. The amino acid multiple
      alignment and phylogenetic analysis showed that this isoform is more similar with
      isoforms in Oreochromis mossambicus, Salmo salar and Anguilla anguilla, and there
      is the highest homologous of 99% between Sarotherodon and Mossambique. The
      predicted protein secondly structure of NKCC1 alpha contains 10 transmenbrane
      domains, which were highly conserved in sequences and locoalization sites
      relatively to other species. The quantitative real time polymerase chain reaction
      (qRT-PCR) assay was developed to estimate the mRNA expression levels in gill,
      liver, intestine and kidney in freshwater, the results showed a tissue-specific
      model. Furthermore, the sanility significantly affects the relative expression
      level of NKCC1 alpha mRNA in gill with a 4.9 times higher in 136 salinity water
      than that in 0 salinity. The results suggest that the NKCC1 alpha is closely
      related to the salt tolerance in S.melanotheron.

PMID- 21174351
TI  - [Temporal stability in song dialects of black redstarts (Phoenicurus ochruros
      rufiventris) in Menyuan, Qinghai Province].
AB  - Bird song dialects provide a useful model for the study of cultural evolution and
      its interactions with genetic evolution. By comparing song dialects over an 8
      year span in the black redstarts (Phoenicurus ochruros rufiventris) of Haibei
      station (37(0)29'N, 101(0)28'E, 3, 200 m a.s.l.) in Menyuan county, Qinghai
      Province,This study examined the temporal stability of the birds'song dialects.
      Songs of black redstarts were recorded from mid-April to late May in 2001 by Uher
      CR 210 tape recorder with Sony directional microphone and in 2009 by Marantz PMD
      670 digital recorder with Sennheiser ME 66 directional microphone. Songs were
      analyzed by using Avisoft-SASLab pro. The similarity of songs between different
      years were analyzed by investigating the sonagram, measuring temporal and
      frequency properties and processing cluster analysis by Spss 10.0 on windows. The
      results showed that species-specific syllable, typical song forms, and the
      typical strophe keep high temporal stability. Males investigated from 2001 and
      2009 shared the entire strophe or some of the syllables. Males sampled from 2009
      have a larger strophe repertoire than that from 2001. The study also indicated
      that the divergence of shared strophe in 2009 is correlated with distance between
      territories. The degree of strophe type sharing and song similarity are higher
      between neighbours than that from more distant males.

PMID- 21174352
TI  - Shape change in viable eggs of the collembolan Folsomia candida provides insight
      into the role of Wolbachia endosymbionts.
AB  - The endosymbiotic bacteria of the genus Wolbachia that infect the collembolan
      species Folsomia candida are responsible for facilitating parthenogenetic
      reproduction in their hosts. This study made empirical observations of the
      development of eggs of F. candida which contained normal populations of Wolbachia
      and of eggs which were cured of Wolbachia by treatment with the antibiotic
      rifampicin. A marked increase in egg size accompanied by a significant change in
      shape from spherical to discoid occurred in viable eggs three to four days after
      laying. These changes did not occur in the universally inviable eggs which came
      from the antibiotic treatment or in the 7% of untreated eggs which were naturally
      inviable. We infer that Wolbachia plays a critical role in zygotic or embryonic
      development during or before the first three days after laying and we draw on
      existing knowledge in speculating on the developmental mechanisms that Wolbachia
      may influence.

PMID- 21174353
TI  - Digestive enzyme and alkaline phosphatase activities during the early stages of
      Silurus soldatovi development.
AB  - To provide a theoretical basis to improve the survival and growth rate and
      optimize diet of sheatfish (Silurus soldatovi), the activities of certain
      digestive enzymes and alkaline phosphatases were investigated during larval
      development of one-ten day old individuals. Results indicated that sheatfish
      larva (~ three days after hatching) had high levels of alkaline protease
      activity, which peaked at five days old and dipped by eight days old, although
      the trend was generally upward. Acid protease activity at one-eight days old was
      low, after which it increased rapidly. Amylase activity reached the highest value
      at five days old, after which it began to decline. Lipase activity fluctuated
      markedly and showed two peaks at three-four days old and six-eight days old.
      Larval digestive enzyme activity and alkaline phosphatase activity were higher
      when fed live food than when fed an artificial diet. Throughout the early
      development process, alkaline protease activity was higher than acid protease,
      alkaline protease and amylase specific activity decreased significantly for eight
      day-old transition larvae, while acid protease activity increased rapidly. These
      results indicate that the changes in digestive enzyme activity were relevant to
      digestive function conversion during fish larvae development. Alkaline
      phosphatase activity showed an upward trend over the first ten days of life,
      which indicated that the gastrointestinal function of sheatfish improved
      gradually.

PMID- 21174354
TI  - Bats and marsupials as indicators of endemism in the Yungas forest of Argentina.
AB  - Several studies have characterized the Yungas as a separate biogeographic unit,
      mainly based in floristic components. However, these characterizations were
      mainly qualitative and did not include faunal groups. The Yungas have been
      assumed as a region with rich floral and faunal diversity, but without testing
      how well they are described by animal distributions. Our study consists of a
      formal analysis of endemism based on distribution of small mammals in the
      southernmost portion of the Yungas. This area is biogeographically very
      interesting because the Yungas are comprised of discontinuous fragments of
      forests that extend into temperate arid and semiarid habitats. As a first
      approximation, we contrasted a group of volant species (bats) versus a group of
      non-volant species (marsupials). Our results show that small mammals are
      efficient indicators of endemism in Yungas. Eighty percent of the species of
      small marsupials included in the analysis supported the identified areas as being
      zones of endemism. Regarding bats, almost 55 percent of the species supported a
      designation of endemism. The results also show that the areas we considered are
      congruent with the botanical definition of the Yungas of northwestern Argentina
      and their subdivisions, an assumption that had not been previously tested with a
      formal quantitative method. We also found that non-volant species are better
      indicators of endemism than volant ones at regional scales, but volant species
      are better indicators than was previously thought.

PMID- 21174355
TI  - Positive influence of traditional culture and socioeconomic activity on
      conservation: a case study from the black-and-white snub-nosed monkey
      (Rhinopithecus bieti) in Tibet.
AB  - Found in the Trans-Himalayas of north-west Yunnan and south-east Tibet, the black
      and-white snub-nosed monkey (Rhinopithecus bieti) is one of the world's most
      endangered primates. A recent survey indicates that only 15 groups with 2500
      individuals remain in the wild. However, the Tibetan Xiaochangdu group may be the
      only equilibrium group in the field since the last investigation in 1988. To
      evaluate the effects of traditional culture and socioeconomic activity on
      biodiversity conservation of R. bieti, we conducted a case study in the
      Honglaxueshan National Nature Reserve in southeast Tibet from June 2003 to May
      2005. Interviews, direct observations, and analysis of socioeconomic data
      indicated major advantages to the conservation of R. bieti, which included that:
      1) traditional culture mainly depended on raising livestock and collecting non
      timber products rather than forest planting of Tibetan highland barley; 2)
      religious beliefs, against to kill any wildlife living on the sacred mountain,
      were mainly influenced by Tibetan Buddhism; and 3) bigger household numbers were
      induced by the polyandrous marriage system, which resulted in lower per capita
      resource consumption than smaller ones.

PMID- 21174356
TI  - Morphological changes of silver and bighead carp in the Yangtze River over the
      past 50 years.
AB  - Multivariate analysis was adopted to analyze 30 morphometrical characteristics of
      121 one-year-old juvenile silver carp (Hypophthalmichthys molitrix) and bighead
      carp (Aristichthys nobilis) bred during the 1950s ("the former population") and
      2008 ("the current population") and collected from the middle reach of the
      Yangtze River. The average discriminant accuracies of the former and current
      silver and bighead carp population were 94.2% and 98.0%, respectively.
      Discriminant analysis also revealed that significant differences in morphology
      occurred between the former and current populations of both carp in overall
      characteristics. One-way analysis of variance indicated that between former and
      current populations, silver carp showed highly significant differences (P<0.01)
      in twelve of their characteristics and significant differences (P<0.05) in eight
      of their characteristics, while bighead carp showed highly significant
      differences (P<0.01) in eight of their characteristics and significant
      differences (P<0.05) in eight of their characteristics. Six head morphology
      variables of the current silver and bighead carp were significantly or highly
      significantly larger than the former populations; fourteen characteristics of
      silver carp and ten characteristics of bighead carp of the current populations,
      mainly reflecting truck and tail morphology, were significantly or very
      significantly smaller than the former populations. Our results indicate that
      silver and bighead carp have developed a larger head and smaller truck and tail
      during the last 50 years. Due to such morphological changes, it seems apparent
      that the heads of these fish species need to be considered in regards to human
      diets, particularly in relation to economic and nutritious value.

PMID- 21174357
TI  - [Species composition and biodiversity of fish community in Dalian Lake,
      Shanghai].
AB  - A field fish survey of Dalian Lake, Shanghai was undertaken in Apr. 11-19, Apr.
      27-May 8 and May 20-29, in total 24,061 fish individuals were collected,
      representing 22 species from 17 genera and 11 families. The dominant specie is
      Carassius auratus, accounting for 76.38% of the total. The eigenvalues of species
      diversity were showing below : Shannon-Wiener's index (H') being 1.0027,
      Simpson's index (lambda) being 0.5959, Pielous's index (J') being 0.3244,
      Margalef's index (D) being 2.0816 and relative rare species (R) being 90.91%. The
      fish community could be classified into 3 ecological types, which including river
      sea migratory fish (3 species), river-lake migratory fish (1 species) and
      sedentary fish (18 species). Also they can be subcategoried into five types
      according to feeding habits, i.e., piscivorous fish (9 species),
      invertebrativorous fish (2 species), omnivores fish (7 species), planktotrophic
      fish (3 species), herbivorous fish (1 species). The results suggested that the
      biodiversity index and fish community stability are both at a low level. Compare
      to the lower reaches of Huangpu River, the proportion of piscivorous fish in
      Dalian Lake is higher, which suggested the water quality of Dalian Lake, located
      in the upper reaches of Huangpu River, is better than that in the downstream.
      It's required to intensify supervision and strengthen the environment protection
      of Dalian Lake to guarantee the sustainable development.

PMID- 21174358
TI  - [Characterization and comparison of the doppler compensation acoustic wave in
      Hipposideros armiger].
AB  - We used the pendulum device to study Doppler-shifted compensation of great leaf
      nosed bat (Hipposideros armiger). The bats' echolocation calls were recorded by
      the Ultrasound Detector both under the rest condition and Doppler shift
      condition. Then we analyzed the calls with Avisoft software. Our results
      suggested that when H. armiger was approaching the target, it showed positive
      Doppler shift compensation: call frequency and the velocity (v) were positive
      correlated. Call frequency fell to minimum when the bats' relative velocity
      reached to maximum; likewise call frequency raised to the resting condition
      frequency when the relative velocity became zero. Negative Doppler shift
      compensation occurred when bats were far away from the target. Under negative
      Doppler shift compensation condition, we found call frequency and velocity were
      positive correlated as well, and moreover, call frequency raised to maximum again
      while the bats had their minus direction's maximal relative velocity. However,
      under this status, the elevated value was much lower than the depressed value
      under positive compensation at the same velocity. The frequency of occurrence of
      negative compensation was obviously less frequent than that under positive
      compensation condition. Therefore, we inferred that the two characteristics of
      the negative Doppler shift compensation mentioned above may be the coactions
      consequence of the bio-structural restriction and natural selection.

PMID- 21174359
TI  - [Food habits and hunting patterns of Tibetan brown bear during warm seasons in
      Kekexili region on Qinghai-Tibetan Plateau].
AB  - Tibetan brown bear (Ursus arctos pruinosus) is an endemic subspecies of brown
      bear on the Qinghai-Tibetan plateau. We once reported a preliminary study on the
      summer food habit of Tibetan brown bear from July to August, 2005 in the Kekexili
      (Hoh Xil).. However, the hunting modes of the Tibetan brawn bear have not been
      reported. From July to August, 2009, we collected additional data on food habits
      and hunting patterns of Tibetan brown bear in the Kekexili region. We found
      Tibetan brown bears are more raptatorial than vegetarian, and their basal food
      was plateau pika (Ochotona curzoniae), relative frequency occurrence of pika in
      the fecal residual of brawn bear was 37.3%, dry weight of pika residuals was
      44.7%, respectively, followed by wild yak (Bos grunniens) , 18.7% and 30.2%, and
      Tibetan antelope (Pantholops hodgsoni) 15.0% and 16.2%. Both prey actively mode
      and scavenge mode were used by Tibetan brown bears in Kekexili. Tibetan brawn
      bears actively dug and hunted for pika and scavenged bodies of wild yak, Tibetan
      antelope and Tibetan gazelle. We observed that Tibetan brawn bears spent about
      10% of their time to dig and to hunt for pika but we had never seen Tibetan brawn
      bears actively hunted large mammals such as wild yak, Tibetan antelope and
      Tibetan gazelle. The total amount of Tibetan antelope, Tibetan gazelle and wild
      yak ingested by Tibetan brown bear through scavenge was about the same amount of
      Plateau pika and Himalayan marmot (Marmota himalayana) eaten by the bear.

PMID- 21174360
TI  - A new record of Dasyatid fish in China: Dasyatis laosensis.
AB  - One specimen was collected from the main course of Lancangjiang River (upper
      reach of Mekong) in Guanlei Port, Xishuangbanna, Yunnan, China in April, 2008. It
      is identified as Dasyatis laosensis, a new record of Dasyatidae species in China.
      It could be distinguished from other Dasyatis species by a combination of the
      following characteristics: one enlarged venomous spine on the tail, ventral
      surface of body with orange marginal coloration, tail length greater than body
      length.

PMID- 21174362
TI  - [Irritable bowel syndrome. Extensive diagnosis is worthwhile].

PMID- 21174361
TI  - ["Doing something good" for the body? Definitely not! Liver damage caused by food
      supplements].

PMID- 21174363
TI  - Proceedings of the 15th Conference of the European Society for Clinical
      Hemorheology and Microcirculation (ESCHM), June 28-July 1, 2009, Pontresina,
      Switzerland.

PMID- 21174364
TI  - Neuroprotection in amyotrophic lateral sclerosis: from pathology to treatment.
      Proceedings of a meeting. September 2009. Pisa, Italy.

PMID- 21174365
TI  - Proceedings of the 29th Northern Ireland Biomedical Engineering Conference.
      Belfast, United Kingdom. April 8, 2009.

PMID- 21174366
TI  - FTIR spectroscopy in microbiological and medical diagnostics. Proceedings of a
      meeting. Berlin, Germany. October 15-16, 2009.

PMID- 21174367
TI  - Commentary on "Hohman LB. The efferent connections of the cerebellar cortex;
      investigations based upon experimental extirpations in the cat. In: The
      cerebellum. An investigation of recent advances. association for research in
      nervous and mental disease, Vol. VI.Williams & Wilkins, Baltimore, 1929, pp. 445
      460".

PMID- 21174368
TI  - Retraction to "Dendrimer nanocarriers as versatile vectors in gene delivery"
      [Nanomedicine: NBM 2010;6:25-34].

PMID- 21174369
TI  - Newly-discovered neuropeptides in the hypothalamus.

PMID- 21174370
TI  - The 13th Biennial Meeting of the International Gynecologic Cancer Society (IGCS
      2010).

PMID- 21174371
TI  - Study of telomerase reverse transcriptase (hTERT) expression in normal, aged, and
      photo-aged skin.
AB  - BACKGROUND: Telomerase is a ribonucleoprotein enzyme capable of extending
      chromosome ends with telomeric DNA sequences. It protects the germline and stem
      cells from senescence by preventing telomere attrition. Cutaneous aging includes
      intrinsic aging, and photo-aging. Telomere-associated cellular senescence
      contributes to certain age-related cutaneous disorders, including increased
      cancer incidence. Premature skin aging in xeroderma pigmentosa (XP) is expected
      to show increased telomere attrition. We aimed to study human telomerase reverse
      transcriptase (hTERT) expression in normal, aged and photo-aged skin and to
      investigate its possible role in the pathogenesis of aging and photo-aging.
      METHODS: hTERT expression using immunohistochemistry was studied in 75 subjects
      comprising four groups: group I, 10 subjects with aged skin; group II, 20
      subjects with photo-aging; group III, Five patients with XP; and group IV, 40
      subjects comprising the control groups. RESULTS: We found positive hTERT in
      normal skin and in the basal and sometimes in supra-basal layers. We reported
      positive hTERT expression in dermal fibroblasts, histiocytes, and skin appendages
      (other than hair follicles) in some cases from all the studied groups. Photo-aged
      and prematurely photo-aged skin showed greater hTERT expression than young and
      aged skin. CONCLUSION: Telomeres rather than telomerase are involved in cellular
      senescence. Yet, telomerase is intimately related to photo-aging in which
      lifetime cumulative sun exposure is an important factor. However, genetic damage
      in XP is the decisive factor and not merely ultraviolet exposure.

PMID- 21174372
TI  - Diphoterine for alkali chemical splashes to the skin at alumina refineries.
AB  - BACKGROUND: Diphoterine is a commercially available amphoteric, hypertonic,
      chelating solution used to decontaminate and irrigate chemical splashes. The aim
      of this study was to evaluate the implementation of Diphoterine at three alumina
      refineries. This is the largest case series reported to date. METHODS: One
      hundred eighty cases of alkali splashes to the skin were evaluated clinically.
      Two groups were compared; those who had applied Diphoterine first and those who
      had applied water first. RESULTS: There were no signs of chemical burn in 52.9%
      of the group who applied Diphoterine first compared with 21.4% of the group who
      applied water first. Only 7.9% of the group who applied Diphoterine first had
      blisters or more severe signs compared with 23.8% of the group who applied water
      first. The differences were statistically significant (P < 0.001). After
      implementation of Diphoterine the "first aid" injury rate for chemical burns fell
      24.7% (95% CI 0.5-43.0%). CONCLUSIONS: Applying Diphoterine first was associated
      with significantly better outcomes following alkali skin splashes than applying
      water first.

PMID- 21174373
TI  - Evaluation of nail disease in psoriatic arthritis by using a modified nail
      psoriasis severity score index.
AB  - BACKGROUND: The Classification of Psoriatic Arthritis Study Group published new
      criteria for classifying psoriatic arthritis (PsA) which included nail psoriasis.
      Our aim was to clarify the clinical importance of nail disease in PsA patients.
      METHODS: We investigated the types and severity of nail disease by using the
      modified nail psoriasis severity score index (mNAPSI) in 23 PsA patients and 23
      patients with uncomplicated psoriasis. We analyzed the relationships of mNAPSI
      with nail fold psoriasis, psoriasis area and severity index score, swollen and/or
      tender joint counts, distal interphalangeal (DIP) joint disease, acute phase
      reactants and the score on the Japanese version of the standard health assessment
      questionnaire. RESULTS: The mNAPSI in 23 PsA patients was higher than that of
      controls (4.8 +/- 5.3 vs. 2.3 +/- 3.7, P < 0.05). The severity of fingernail
      disease in PsA patients was significantly associated with DIP joint disease (8.6
      +/- 5.9 vs. 3.1 +/- 3.3, P < 0.05) and nail fold psoriasis (6.7 +/- 5.2 vs. 3.5
      +/- 5.2, P < 0.05). There were no correlations between the mNAPSI and other
      systemic involvements. CONCLUSIONS: The nail involvement and prolonged nail bed
      psoriasis were common in PsA patients. Nail fold psoriasis and DIP joint
      arthritis were associated with nail involvement in PsA patients. Nail psoriasis
      would be related to the Koebner phenomenon and local inflammatory DIP joint
      arthritis in PsA patients, and we suggested that nail involvement in PsA was
      among the disorders indicative of distal phalanx enthesitis.

PMID- 21174374
TI  - Cutaneous melanoma with nodal metastases in elderly people.
AB  - BACKGROUND: The impact of age on melanoma patient outcomes is uncertain.
      OBJECTIVE: The aim of the study was to analyze the characteristics and treatment
      outcomes in cutaneous melanoma patients >= 65 years of age with lymph node
      metastases. METHODS: We analyzed data from 849 consecutive patients with stage
      III cutaneous melanoma who were treated between 1994 and 2007 at one institution.
      Of these, 225 (26.5%) were >= 65 years of age. The characteristics and disease
      specific survival (DSS) from lymph node dissection (LND) date of patients >= 65
      years of age were compared with those of younger patients. Median follow-up time
      was 49 months (range: 6-140 months). RESULTS: In the >= 65 years group (51.6%
      men), the median Breslow thickness was 5.0 mm and 70% was ulcerated. The 5-year
      DSS rate was significantly lower in older patients (34%). Multivariate analysis
      identified older age as an independent prognostic factor for DSS in the overall
      group. Independent negative prognostic factors of DSS in the group of older stage
      III patients were identified as features of nodal metastases (extracapsular
      invasion, HR = 1.74, P = 0.009; and >= 4 involved lymph nodes, HR = 1.5; P =
      0.008) and male sex (HR = 1.5; P = 0.039). CONCLUSIONS: This analysis showed that
      melanoma patients >= 65 years of age are characterized by a higher primary tumor
      stage and worse prognosis in the presence of regional node metastases than
      younger patients. Additionally, the results indicate that the same radical
      surgical therapy is necessary for patients >= 65 years old as in younger
      patients.

PMID- 21174375
TI  - Two cases of dermatomyofibroma (plaque-like dermal fibromatosis).
AB  - BACKGROUND: Dermatomyofibroma is a rare but distinct benign cutaneous mesenchymal
      neoplasm of fibroblastic/myofibroblastic differentiation. It is more common in
      adolescents and young adults, with a female preponderance. In most cases, the
      lesions are asymptomatic and small, measuring from 10 to 20 mm. Early and active
      lesions tend to be actin positive. CASE REPORT: We present a) a new case of
      dermatomyofibroma in an 11-month-old male infant, the youngest case reported to
      date, and b) the second reported case of a giant annular dermatomyofibroma,
      measuring 10 cm * 6 cm, in a 52-year-old woman. In both cases, histological
      examination showed a spindle-cell proliferation embedded among the collagen
      fibers of the dermis, arranged predominantly parallel to the skin surface. In
      both cases the spindle cells stained positive for smooth muscle actin and the
      elastic fibers were increased and fragmented. CONCLUSION: Dermatologists and
      pediatricians should be aware of this benign entity in order to avoid unnecessary
      treatment.

PMID- 21174376
TI  - Myelosarcoma in Fanconi anemia.

PMID- 21174377
TI  - US cancer organisations weigh-in on health-care reform law.

PMID- 21174378
TI  - Cancer and cultural differences.

PMID- 21174379
TI  - Proceedings of the 2009 International Conference on Intelligent Computing (ICIC).
      September 16-19, 2009. Ulsan, Korea.

PMID- 21174380
TI  - More common questions on electronic health records.

PMID- 21174383
TI  - Marine revelations.

PMID- 21174381
TI  - Creating loyalty is a difficult undertaking.

PMID- 21174385
TI  - Nightshift breast cancer, flour dust and blue-light risk.

PMID- 21174386
TI  - British government scraps advice bodies.

PMID- 21174387
TI  - Fears over new Galapagos status.

PMID- 21174388
TI  - Cloned cow  controversy.

PMID- 21174389
TI  - Alex Kacelnik.

PMID- 21174390
TI  - Characterization of gas-expanded liquid-deposited gold nanoparticle films on
      substrates of varying surface energy.
AB  - Dodecanethiol-stabilized gold nanoparticles (AuNPs) were deposited via a gas
      expanded liquid (GXL) technique utilizing CO(2)-expanded hexane onto substrates
      of different surface energy. The different surface energies were achieved by
      coating silicon (100) substrates with various organic self-assembled monolayers
      (SAMs). Following the deposition of AuNP films, the films were characterized to
      determine the effect of substrate surface energy on nanoparticle film deposition
      and growth. Interestingly, the critical surface tension of a given substrate does
      not directly describe nanoparticle film morphology. However, the results in this
      study indicate a shift between layer-by-layer and island film growth based on the
      critical surface tension of the capping ligand. Additionally, the fraction of
      surface area covered by the AuNP film decreases as the oleophobic nature of the
      surfaces increases. On the basis of this information, the potential exists to
      engineer nanoparticle films with desired morphologies and characteristics.

PMID- 21174391
TI  - One-dimensional semiconductor nanostructure based thin-film partial composite
      formed by transfer implantation for high-performance flexible and printable
      electronics at low temperature.
AB  - Having high bending stability and effective gate coupling, the one-dimensional
      semiconductor nanostructures (ODSNs)-based thin-film partial composite was
      demonstrated, and its feasibility was confirmed through fabricating the Si NW
      thin-film partial composite on the poly(4-vinylphenol) (PVP) layer, obtaining
      uniform and high-performance flexible field-effect transistors (FETs). With the
      thin-film partial composite optimized by controlling the key steps consisting of
      the two-dimensional random dispersion on the hydrophilic substrate of ODSNs and
      the pressure-induced transfer implantation of them into the uncured thin
      dielectric polymer layer, the multinanowire (NW) FET devices were simply
      fabricated. As the NW density increases, the on-current of NW FETs increases
      linearly, implying that uniform NW distribution can be obtained with random
      directions over the entire region of the substrate despite the simplicity of the
      drop-casting method. The implantation of NWs by mechanical transfer printing onto
      the PVP layer enhanced the gate coupling and bending stability. As a result, the
      enhancements of the field-effect mobility and subthreshold swing and the stable
      device operation up to a 2.5 mm radius bending situation were achieved without an
      additional top passivation.

PMID- 21174392
TI  - Application of catalytic dynamic resolution of N-Boc-2-lithiopiperidine to the
      asymmetric synthesis of 2-aryl and 2-vinyl piperidines.
AB  - The highly enantioselective synthesis of 2-aryl- and 2-vinyl-piperidines has been
      accomplished through a catalytic dynamic resolution (CDR) of N-Boc-2
      lithiopiperidine. The method has been applied to the synthesis of both
      enantiomers of the tobacco alkaloid anabasine.

PMID- 21174393
TI  - An approach to the bis-oxazole macrocycle of diazonamides.
AB  - A convergent approach to a macrocyclic compound embodying the complete "eastern"
      quadrant of diazonamides is described. The opening sequence in this work relies
      on an oxazole-forming reaction devised earlier in this group, while a late step
      involves a Robinson-Gabriel cyclization of an amidoketone to form a second
      oxazole.

PMID- 21174395
TI  - Novel electrochemical deoxygenation reaction using diphenylphosphinates.
AB  - The electrochemical reduction of diphenylphosphinate esters leads smoothly and in
      high yields to the corresponding deoxygenated products. In comparison with the
      previously developed methodologies, the electrolysis could be performed at lower
      temperature and with a higher current density, resulting in a shorter reaction
      time.

PMID- 21174394
TI  - Histone deacetylase inhibitors as a tool to up-regulate new fungal biosynthetic
      products: isolation of EGM-556, a cyclodepsipeptide, from Microascus sp.
AB  - The histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA)
      was used to turn on the biosynthesis of EGM-556, a new cyclodepsipeptide of
      hybrid biosynthetic origin, isolated from the Floridian marine sediment-derived
      fungus Microascus sp. The absolute configurations of three chiral centers were
      determined by Marfey's derivatization. EGM-556 represents one of the few examples
      in which silent biosynthetic genes, encoding a new secondary metabolite, were
      activated by means of epigenetic manipulation of the fungal metabolome.

PMID- 21174396
TI  - An efficient copper-catalyzed carbon-sulfur bond formation protocol in water.
AB  - An efficient protocol of copper-catalyzed C-S bond formation between aryl halides
      and potassium thiocyanate leading to diaryl sulfides is reported. A variety of
      diaryl sulfides can be synthesized in good to excellent yields up to 94%.

PMID- 21174397
TI  - Synthesis and stereochemical assignment of (+)-chamuvarinin.
AB  - A stereocontrolled total synthesis of (+)-chamuvarinin, isolated from the root
      extract of Uvaria Chamae, utilizes a convergent modular strategy to construct the
      adjacently linked C15-C28 ether array, followed by a late-stage Julia-Kocienski
      olefination to append the butenolide motif. This constitutes the first total
      synthesis of (+)-chamuvarinin, defining the relative and absolute configuration
      of this unique annonaceous acetogenin.

PMID- 21174398
TI  - Global structure of forked DNA in solution revealed by high-resolution single
      molecule FRET.
AB  - Branched DNA structures play critical roles in DNA replication, repair, and
      recombination in addition to being key building blocks for DNA nanotechnology.
      Here we combine single-molecule multiparameter fluorescence detection and
      molecular dynamics simulations to give a general approach to global structure
      determination of branched DNA in solution. We reveal an open, planar structure of
      a forked DNA molecule with three duplex arms and demonstrate an ion-induced
      conformational change. This structure will serve as a benchmark for DNA-protein
      interaction studies.

PMID- 21174399
TI  - Side-chain cross-linked short alpha-helices that behave like original proteins in
      biomacromolecular interactions.
AB  - We explored the effect of alpha-helical stabilization upon the binding of short
      peptides to DNAs. The short peptides were designed according to the binding
      domains of DNA-binding proteins and were cross-linked between their side chains
      with diacetylenic or isophthalic cross-linking agents to keep stable alpha
      helices. The binding abilities of the peptides to DNAs were evaluated by
      fluorescence resonance energy transfer analysis. When a cross-linked peptide
      based on the homeodomain of the transcription factor was titrated with a target
      DNA duplex, its dissociation constant (Kd) was calculated to be ~0.5 nM. This
      value was the double-digit smaller than that of the corresponding non-cross
      linked peptide. The cross-linked peptide showed high substrate specificity for
      DNAs at the same level as the original DNA-binding protein.

PMID- 21174400
TI  - Evidence for a trianion intermediate in the metalation of 4-hydroxy-6,7-dimethoxy
      8-methyl-2-naphthoic acid. Methodology and application to racemic 5,5'
      didesisopropyl-5,5'-dialkylapogossypol derivatives.
AB  - The metalation of 4-hydroxy-6,7-dimethoxy-8-methyl-2-naphthoic acid (8) affording
      trianion 6 is presented and applied to the regioselective efficient construction
      of a series of 5,5'-didesisopropyl-5,5'-dialkylapogossypol derivatives 3 that are
      potent pan-active inhibitors of antiapoptotic Bcl-2 family proteins.

PMID- 21174401
TI  - A novel multidimensional protein identification technology approach combining
      protein size exclusion prefractionation, peptide zwitterion-ion hydrophilic
      interaction chromatography, and nano-ultraperformance RP chromatography/nESI-MS2
      for the in-depth analysis of the serum proteome and phosphoproteome: application
      to clinical sera derived from humans with benign prostate hyperplasia.
AB  - The current proof-of-principle study was aimed toward development of a novel
      multidimensional protein identification technology (MudPIT) approach for the in
      depth proteome analysis of human serum derived from patients with benign prostate
      hyperplasia (BPH) using rational chromatographic design principles. This study
      constituted an extension of our published work relating to the identification and
      relative quantification of potential clinical biomarkers in BPH and prostate
      cancer (PCa) tissue specimens. The proposed MudPIT approach encompassed the use
      of three distinct yet complementary liquid chromatographic chemistries. High
      pressure size-exclusion chromatography (SEC) was used for the prefractionation of
      serum proteins followed by their dialysis exchange and solution phase trypsin
      proteolysis. The tryptic peptides were then subjected to offline zwitterion-ion
      hydrophilic interaction chromatography (ZIC-HILIC) fractionation followed by
      their online analysis with reversed-phase nano-ultraperformance chromatography
      (RP-nUPLC) hyphenated to nanoelectrospray ionization-tandem mass spectrometry
      using an ion trap mass analyzer. For the spectral processing, the sequential use
      of the SpectrumMill, Scaffold, and InsPecT software tools was applied for the
      tryptic peptide product ion MS(2) spectral processing, false discovery rate (FDR)
      assessment, validation, and protein identification. This milestone serum analysis
      study allowed the confident identification of over 1955 proteins (p <= 0.05; FDR
      <= 5%) with a broad spectrum of biological and physicochemical properties
      including secreted, tissue-specific proteins spanning approximately 12 orders of
      magnitude as they occur in their native abundance levels in the serum matrix.
      Also encompassed in this proteome was the confident identification of 375
      phosphoproteins (p <= 0.05; FDR <= 5%) with potential importance to cancer
      biology. To demonstrate the performance characteristics of this novel MudPIT
      approach, a comparison was made with the proteomes resulting from the
      immunodepletion of the high abundant albumin and IgG proteins with offline first
      dimensional tryptic peptide separation with both ZIC-HILIC and strong cation
      exchange (SCX) chromatography and their subsequent online RP-nUPLC-nESI-MS(2)
      analysis.

PMID- 21174402
TI  - General method for labeling siRNA by click chemistry with fluorine-18 for the
      purpose of PET imaging.
AB  - The alkyne-azide Cu(I)-catalyzed Huisgen cycloaddition, a click-type reaction,
      was used to label a double-stranded oligonucleotide (siRNA) with fluorine-18. An
      alkyne solid support CPG for the preparation of monostranded oligonucleotides
      functionalized with alkyne has been developed. Two complementary azide labeling
      agents (1-(azidomethyl)-4-[(18)F]fluorobenzene) and 1-azido-4-(3
      [(18)F]fluoropropoxy)benzene have been produced with 41% and 35% radiochemical
      yields (decay-corrected), respectively. After annealing with the complementary
      strand, the siRNA was directly labeled by click chemistry with [(18)F]fluoroazide
      to produce the [(18)F]-radiolabeled siRNA with excellent radiochemical yield and
      purity.

PMID- 21174403
TI  - Synthesis of metal-organic complex arrays.
AB  - The Merrifield solid-phase peptide synthesis technique has been adapted to the
      synthesis of homo- and heterometallic metal-organic complex arrays (MOCAs). A
      terpyridine-appended and Fmoc-protected L-tyrosine derivative was metalated with
      Pt(II), Rh(III), or Ru(II) ions in solution and sequentially coupled at the
      surface of functionalized polymeric resin to give a metal complex triad (Rh-Pt
      Ru), tetrad (Ru-Rh-Pt-Pt), pentad (Rh-Pt-Ru-Pt-Rh), and hexad (Rh-Pt-Ru-Pt-Rh-Pt)
      with specific metal sequence arrangements. These were cleaved from the resin, and
      their character was confirmed by mass spectrometry.

PMID- 21174404
TI  - Subsurface imaging of soft polymeric materials with nanoscale resolution.
AB  - Nondestructive depth-resolved imaging of ~20-nm-thick surface layers of soft
      polymeric materials is demonstrated using amplitude modulation atomic force
      microscopy (AM-AFM). From a map of amplitude-phase-distance curves, the tip
      indentation into the specimen is determined. This serves as a depth coordinate
      for reconstructing cross sections and volume images of the specimen's mechanical
      properties. Our method reveals subsurface structures which are not discernible
      using conventional AM-AFM. Results for surfaces of a block copolymer and a
      semicrystalline polymer are presented.

PMID- 21174405
TI  - Interaction between metal and graphene: dependence on the layer number of
      graphene.
AB  - The interaction between graphene and metal was investigated by studying the G
      band splitting in surface-enhanced Raman scattering (SERS) spectra of single-, bi
      , and trilayer graphene. The Ag deposition on graphene induced large enhancement
      of the Raman signal of graphene, indicating SERS of graphene. In particular, the
      G band was split into two distinct peaks in the SERS spectrum of graphene. The
      extent of the G band splitting was 13.0 cm(-1) for single-layer, 9.6 cm(-1) for
      bilayer, and 9.4 cm(-1) for trilayer graphene, whereas the G band in the SERS
      spectrum of a thick multilayer was not split. The average SERS enhancement factor
      of the G band was 24 for single-layer, 15 for bilayer, and 10 for trilayer
      graphene. These results indicate that there is a correlation between SERS
      enhancement factor and the extent of the G band splitting, and the strongest
      interaction occurs between Ag and single-layer graphene. Furthermore, the Ag
      deposition on graphene can induce doping of graphene. The intensity ratio of 2D
      and G bands (I(2D)/I(G)) decreased after Ag deposition on graphene, indicating
      doping of graphene. From changes in positions of G and 2D bands after the metal
      deposition on graphene, Ag deposition induced n-doping of graphene, whereas Au
      deposition induced p-doping.

PMID- 21174406
TI  - Facet-dependent and au nanocrystal-enhanced electrical and photocatalytic
      properties of Au-Cu2O core-shell heterostructures.
AB  - We report highly facet-dependent electrical properties of Cu(2)O nanocubes and
      octahedra and significant enhancement of gold nanocrystal cores to the electrical
      conductivity of Au-Cu(2)O core-shell octahedra. Cu(2)O nanocubes and octahedra
      and Au-Cu(2)O core-shell cubes and octahedra were synthesized by following our
      reported facile procedures at room temperature. Two oxide-free tungsten probes
      attached to a nanomanipulator installed inside a scanning electron microscope
      made contacts to a single Cu(2)O nanocrystal for the I-V measurements. Pristine
      Cu(2)O octahedra bounded by {111} facets are 1100 times more conductive than
      pristine Cu(2)O cubes enclosed by {100} faces, which are barely conductive. Core
      shell cubes are only slightly more conductive than pristine cubes. A 10,000-fold
      increase in conductivity over a cube has been recorded for an octahedron.
      Remarkably, core-shell octahedra are far more conductive than pristine octahedra.
      The same facet-dependent electrical behavior can still be observed on a single
      nanocrystal exposing both {111} and {100} facets. This new fundamental property
      may be observable in other semiconductor nanocrystals. We also have shown that
      both core-shell cubes and octahedra outperform pristine cubes and octahedra in
      the photodegradation of methyl orange. Efficient photoinduced charge separation
      is attributed to this enhanced photocatalytic activity. Interestingly, facet
      selective etching occurred over the {100} corners of some octahedra and core
      shell octahedra during photocatalysis. The successful preparation of Au-Cu(2)O
      core-shell heterostructures with precise shape control has offered opportunities
      to discover new and exciting physical and chemical properties of nanocrystals.

PMID- 21174407
TI  - Isolation, structure elucidation, and cytotoxic evaluation of
      furanonaphthoquinones from in vitro plantlets and cultures of Streptocarpus
      dunnii.
AB  - Two new furanonaphthoquinones, (3R)-7-methoxy-alpha-dunnione (5) and (3R)-6
      hydroxy-7-methoxy-alpha-dunnione (6), along with the known (3R)-dunnione (1),
      (3R)-alpha-dunnione (2), (3R)-7-hydroxy-alpha-dunnione (3), and 1-hydroxy-2
      methylanthraquinone (4), were isolated from in vitro cultures of Streptocarpus
      dunnii. The structures of compounds 5 and 6 were established by spectroscopic
      means. This is the first report of hydroxylated furanonaphthoquinones in a
      Streptocarpus species. Compounds 1-3 demonstrated cytotoxic activity against a
      range of breast cancer and pancreatic tumor cell lines.

PMID- 21174408
TI  - Radical scavenging and antioxidant activities of isocoumarins and a phthalide
      from the endophytic fungus Colletotrichum sp.
AB  - Five known isocoumarins, monocerin (1), derivative 2, and fusarentin derivatives
      3-5, and a new phthalide (6) were isolated from the endophytic fungus
      Colletotrichum sp. 2 selectively exhibited cytotoxic activity toward the HepG2
      cell line. Compounds 2 and 4 scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) free
      radicals (IC(50) values of 23.4 and 16.4 MUM, respectively) and inhibited
      superoxide anion radical formation (IC(50) values of 52.6 and 4.3 MUM,
      respectively). The C-7 hydroxyl group in 2 and 4 might be important for radical
      scavenging activities. Isocoumarins 1-3 and phthalide 6 showed potent antioxidant
      activity.

PMID- 21174409
TI  - Laser thinning for monolayer graphene formation: heat sink and interference
      effect.
AB  - Despite the availability of large-area graphene synthesized by chemical vapor
      deposition (CVD), the control of a uniform monolayer graphene remained
      challenging. Here, we report a method of acquiring monolayer graphene by laser
      irradiation. The accumulation of heat on graphene by absorbing light, followed by
      oxidative burning of upper graphene layers, which strongly relies on the
      wavelength of light and optical parameters of the substrate, was in situ measured
      by the G-band shift in Raman spectroscopy. The substrate plays a crucial role as
      a heat sink for the bottom monolayer graphene, resulting in no burning or
      etching. Oscillatory thinning behavior dependent on the substrate oxide thickness
      was evaluated by adopting a simple Fresnel's equation. This paves the way for
      future research in utilizing monolayer graphene for high-speed electronic
      devices.

PMID- 21174410
TI  - Determination of the polar and total surface energy distributions of particulates
      by inverse gas chromatography.
AB  - This Letter reports a technique of measuring polar surface energy distributions
      of lactose using inverse gas chromatography (IGC). The significance of this study
      is that the total surface energy distributions can now be characterized by
      combining the already known dispersive surface energy distribution with polar
      surface energy distribution determined in this study. The polar surface energy
      was calculated from the specific free energies for surface interactions with a
      monopolar basic probe, ethyl acetate, and a monopolar acidic probe,
      dichloromethane.

PMID- 21174411
TI  - Heteroepitaxial growth of high-index-faceted palladium nanoshells and their
      catalytic performance.
AB  - The development of high-performance nanocatalysts relies essentially on the
      generation of stable and active surface sites at the atomic scale through
      synthetic control of the size, shape, and chemical composition of nanoscale
      metals and metal oxides. One promising route is to induce the exposure of
      catalytically active high-index facets of nanostructures through shape-controlled
      syntheses. We have designed and prepared two types of Pd nanoshells that are
      enclosed by high-index {730} and {221} facets through heteroepitaxial growth on
      high-index-faceted Au nanocrystals. The turnover numbers per surface atom of the
      high-index-faceted Pd nanoshells have been found to be 3-7 times those of Pd and
      Au-Pd core-shell nanocubes that possess only {100} facets in catalyzing the
      Suzuki coupling reaction. These results open up a potential for the development
      of inexpensive and highly active metal nanocatalysts.

PMID- 21174412
TI  - Importance of a serine proximal to the C(4a) and N(5) flavin atoms for hydride
      transfer in choline oxidase.
AB  - Choline oxidase catalyzes the flavin-dependent, two-step oxidation of choline to
      glycine betaine with the formation of an aldehyde intermediate. In the first
      oxidation reaction, the alcohol substrate is initially activated to its alkoxide
      via proton abstraction. The substrate is oxidized via transfer of a hydride from
      the alkoxide alpha-carbon to the N(5) atom of the enzyme-bound flavin. In the
      wild-type enzyme, proton and hydride transfers are mechanistically and
      kinetically uncoupled. In this study, we have mutagenized an active site serine
      proximal to the C(4a) and N(5) atoms of the flavin and investigated the reactions
      of proton and hydride transfers by using substrate and solvent kinetic isotope
      effects. Replacement of Ser101 with threonine, alanine, cysteine, or valine
      resulted in biphasic traces in anaerobic reductions of the flavin with choline
      investigated in a stopped-flow spectrophotometer. Kinetic isotope effects
      established that the kinetic phases correspond to the proton and hydride transfer
      reactions catalyzed by the enzyme. Upon removal of Ser101, there is an at least
      15-fold decrease in the rate constants for proton abstraction, irrespective of
      whether threonine, alanine, valine, or cysteine is present in the mutant enzyme.
      A logarithmic decrease spanning 4 orders of magnitude is seen in the rate
      constants for hydride transfer with increasing hydrophobicity of the side chain
      at position 101. This study shows that the hydrophilic character of a serine
      residue proximal to the C(4a) and N(5) flavin atoms is important for efficient
      hydride transfer.

PMID- 21174413
TI  - Dissection of complex molecular recognition interfaces.
AB  - The synthesis of a family of zinc porphyrins and pyridine ligands equipped with
      peripheral H-bonding functionality has provided access to a wide range of closely
      related supramolecular complexes featuring between zero and four intramolecular H
      bonds. An automated UV/vis titration system was used to characterize 120
      different complexes, and these data were used to construct a large of number of
      different chemical double mutant cycles to quantify the intramolecular H-bonding
      interactions. The results probe the quantitative structure-activity relationship
      that governs cooperativity in the assembly of complex molecular recognition
      interfaces. Specifically, variations in the chemical structures of the complexes
      have allowed us to change the supramolecular architecture, conformational
      flexibility, geometric complementarity, the number and nature of the H-bond
      interactions, and the overall stability of the complex. The free energy
      contributions from individual H-bonds are additive, and there is remarkably
      little variation with architecture in the effective molarity for the formation of
      intramolecular interactions. Intramolecular H-bonds are not observed in complexes
      where they are geometrically impossible, but there are no cases where excellent
      geometric complementarity leads to very high affinities. Similarly, changes in
      conformational flexibility seem to have limited impact on the values of effective
      molarity (EM). The major variation that was found for all of the 48
      intramolecular interactions that were examined using double mutant cycles is that
      the values of EM for intramolecular carboxylate ester-phenol H-bonds (200 mM) are
      an order of magnitude larger than those found for phosphonate diester-phenol H
      bonds (30 mM). The corresponding intermolecular phosphonate diester-phenol H
      bonds are 2 orders of magnitude more stable than carboxylate ester-phenol H
      bonds, and the large differences in EM may be due to some kind of compensation
      effect, where the stronger H-bond is harder to make, because it imposes tighter
      constraints on the geometry of the complex.

PMID- 21174414
TI  - Spontaneous and selective CO2 sorption under ambient conditions in seemingly
      nonporous molecular crystal of azacalix[5]arene pentamethyl ether.
AB  - Described are the syntheses, crystal structures, and solid-gas adsorption
      behaviors of azacalix[4]arene tetramethyl ether and azacalix[5]arene pentamethyl
      ether. While the former compound exhibited no adsorption of four main atmospheric
      components, the latter selectively and rapidly adsorbed CO(2) at ambient
      temperature and pressure. X-ray crystallographic and potential energy
      distribution analysis revealed that azacalix[5]arene created an energetically
      favorable space for CO(2) in its seemingly nonporous crystal, leading to the
      observed selective CO(2) uptake under ambient conditions.

PMID- 21174415
TI  - Steric and electronic effects in capsule-confined green fluorescent protein
      chromophores.
AB  - The turn-on of emission in fluorescent protein chromophores sequestered in an
      "octaacid" capsule is controlled by stereoelectronic effects described by a
      linear free energy relationship. The stereochemical effects are governed by both
      the positions and volumes of the aryl substituents, while the electronic effects,
      including ortho effects, can be treated with Hammett sigma parameters. The use of
      substituent volumes rather than A values reflects packing of the molecule within
      the confines of the capsule.

PMID- 21174416
TI  - Copper-catalyzed direct sulfoximination of azoles and polyfluoroarenes under
      ambient conditions.
AB  - The direct dehydrogenative C-N coupling of azoles or polyfluoroarenes with N-H
      sulfoximines proceeds effectively in the presence of a copper catalyst at room
      temperature under air to afford the corresponding N-arylsulfoximines in good to
      high yields.

PMID- 21174418
TI  - Crystal structure based design of signal enhancement schemes for solid-state NMR
      of insensitive half-integer quadrupolar nuclei.
AB  - A combination of density functional and optimal control theory has been used to
      generate amplitude- and phase-modulated excitation pulses tailored specifically
      for the (33)S nuclei in taurine, based on one of several reported crystal
      structures. The pulses resulted in significant signal enhancement (stemming from
      population transfer from the satellite transitions) without the need for any
      experimental optimization. This allowed an accurate determination of the (33)S
      NMR interaction parameters at natural abundance and at a moderate magnetic field
      strength (11.7 T). The (33)S NMR parameters, along with those measured from (14)N
      using frequency-swept pulses, were then used to assess the accuracy of various
      proposed crystal structures.

PMID- 21174417
TI  - Enantioselective total synthesis of (+)-salvileucalin B.
AB  - An enantioselective total synthesis of the diterpenoid natural product (+)
      salvileucalin B is reported. Key findings include a copper-catalyzed arene
      cyclopropanation reaction to provide the unusual norcaradiene core and a
      reversible retro-Claisen rearrangement of a highly functionalized norcaradiene
      intermediate.

PMID- 21174419
TI  - Combined experimental and computational study of intramolecular charge transfer
      in p-N,N-dimethylamino-p'-cyano-diphenylacetylene.
AB  - A concerted experi-mental (time-resolved spectroscopies) and computational
      (TDDFT) study of p-N,N-dimethylamino-p'-cyano-diphenylacetylene (DACN-DPA) has
      been carried out to probe the intramolecular charge transfer (ICT) reaction that
      occurs in polar solvents. The picosecond transient absorption, as well as
      fluorescence, in acetonitrile reveals the formation of a twisted ICT(sigma*)
      state, which involves transfer of an electron from the 4
      (dimethylamino)benzethyne moiety (DMAB) to the benzonitrile (BN) group. This
      ICT(sigma*) state, with a large dipole moment (24.7 D) and a geometry in which
      the plane of electron-accepting BN group is perpendicular to the plane electron
      donating DMAB moiety and the angles of C(DMAB)C=C is 135.0 degrees , is
      responsible for the greatly Stokes-shifted (~8000 cm(-1)) fluorescence and the
      transient absorption bands (with peaks at about 630 and 425 nm), which decays
      with the same lifetime (~780 ps). It is proposed that the 630 nm picosecond
      transient absorption of the ICT state represents the absorption spectrum of
      dimethylaminobenzethyne radical cation and the 425 nm transient represents the
      absorption spectrum of benzonitrile radical anion. In nonpolar n-hexane, most of
      the fluorescence as well as the major component of the transient absorption
      originate from the S(1) (pipi*) state.

PMID- 21174420
TI  - A highly selective and sensitive fluorescence sensing system for distinction
      between diphosphate and nucleoside triphosphates.
AB  - Among the numerous chemosensors available for diphosphate (P(2)O(7)(4-), PPi) and
      nucleoside triphosphates (NTPs), only a few can distinguish between PPi and NTPs.
      Hence, very few bioanalytical applications based on such selective chemosensors
      have been realized. We have developed a new fluorescence sensing system for
      distinction between PPi and NTPs based on the combination of two sensors, a
      binuclear Zn(II) complex (1.2Zn) and boronic acid (BA), in which one chemosensor
      (1.2Zn) shows signal changes depending on the PPi (or NTP) concentration, and the
      other (BA) blocks the signal change caused by NTPs; this system enables the
      distinction of PPi from NTPs and is sensitive to nanomolar concentrations of PPi.
      The new sensing system has been successfully used for the direct quantification
      of RNA polymerase activity.

PMID- 21174422
TI  - A computational study of the heats of reaction of substituted monoethanolamine
      with CO2.
AB  - Various amines have been considered as materials for chemical capture of CO(2)
      through liquid-phase reactions to form either carbamate or carbamic acid
      products. One of the main challenges in these CO(2)-amine reactions lies in
      tuning the heat of reaction to achieve the correct balance between the extent of
      reaction and the energy cost for regeneration. In this work, we use a
      computational approach to study the effect of substitution on the heats of
      reaction of monoethanolamine (MEA). We use ab initio methods at the MP2/aug-cc
      pVDZ level, coupled with geometries generated from B3LYP/6-311++G(d,p) density
      functional theory along with the conductor-like polarizable continuum model to
      compute the heats of reaction. We consider two possible reaction products:
      carbamate, having a 2:1 amine:CO(2) reaction stoichiometry, and carbamic acid,
      having a 1:1 stoichiometry. We have considered CH(3), NH(2), OH, OCH(3), and F
      substitution groups at both the alpha- and beta-carbon positions of MEA. We have
      experimentally measured heats of reaction for MEA and both alpha- and beta-CH(3)
      substituted MEA to test the predictions of our model. We find quantitative
      agreement between the predictions and experiments. We have also computed the
      relative basicities of the substituted amines and found that the heats of
      reaction for both carbamate and carbamic acid products are linearly correlated
      with the computed relative basicities. Weaker basicities result in less
      exothermic heats of reaction. Heats of reaction for carbamates are much more
      sensitive to changes in basicity than those for carbamic acids. This leads to a
      crossover in the heat of reaction so that carbamic acid formation becomes
      thermodynamically favored over carbamate formation for the weakest basicities.
      This provides a method for tuning the reaction stoichiometry from 2:1 to 1:1.

PMID- 21174421
TI  - Calculation of local water densities in biological systems: a comparison of
      molecular dynamics simulations and the 3D-RISM-KH molecular theory of solvation.
AB  - Water plays a unique role in all living organisms. Not only is it nature's
      ubiquitous solvent, but it also actively takes part in many cellular processes.
      In particular, the structure and properties of interfacial water near
      biomolecules such as proteins are often related to the function of the respective
      molecule. It can therefore be highly instructive to study the local water density
      around solutes in cellular systems, particularly when solvent-mediated forces
      such as the hydrophobic effect are relevant. Computational methods such as
      molecular dynamics (MD) simulations seem well suited to study these systems at
      the atomic level. However, due to sampling requirements, it is not clear that MD
      simulations are, indeed, the method of choice to obtain converged densities at a
      given level of precision. We here compare the calculation of local water
      densities with two different methods: MD simulations and the three-dimensional
      reference interaction site model with the Kovalenko-Hirata closure (3D-RISM-KH).
      In particular, we investigate the convergence of the local water density to
      assess the required simulation times for different levels of resolution.
      Moreover, we provide a quantitative comparison of the densities calculated with
      MD and with 3D-RISM-KH and investigate the effect of the choice of the water
      model for both methods. Our results show that 3D-RISM-KH yields density
      distributions that are very similar to those from MD up to a 0.5 A resolution,
      but for significantly reduced computational cost. The combined use of MD and 3D
      RISM-KH emerges as an auspicious perspective for efficient solvent sampling in
      dynamical systems.

PMID- 21174424
TI  - Direct observation by laser scanning confocal microscopy of microstructure and
      phase migration of PVC gels in an applied electric field.
AB  - The fluorescent probe lucigenin was incorporated in poly(vinyl chloride) (PVC)
      gels, and laser scanning confocal microscopy (LSCM) was used to clarify the
      internal structures of the gels. From the two-dimensional and three-dimensional
      information by LSCM, we first observed the internal structure of the PVC gel at a
      wet status, where the PVC gels comprised a polymer-rich phase and a polymer-poor
      phase uniformly with a three-dimensional network structure. After an electric
      field was applied, an effect of the electric field resulted in the change of
      internal structure in the gels. The polymer-poor phase moved from the cathode to
      the anode and the polymer-rich phase formed linelike arrangement between
      electrodes due to the attraction force. On the other hand, the freeze-dried PVC
      gels with/without in-situ dc voltage casting were particularly fabricated to
      confirm above results by the field emission scanning electron microscopy (FE
      SEM). It was found that many craters remained on the surface of the gel near the
      anode due to sublimation in freeze-drying. This phenomenon did not appear on the
      surface near the cathode. The results of in-situ dc voltage casting also
      suggested that a substantial amount of polymer-poor phase was moved and fixed at
      the anode. Thus, results of both LSCM and in-situ dc voltage casting corresponded
      to the effect of electric field on PVC gels and provided a convincing evidence
      for the interpretation of the deformation mechanism of PVC gel actuators by an
      applied electric field.

PMID- 21174423
TI  - Dual amplification strategy for the fabrication of highly sensitive interleukin-6
      amperometric immunosensor based on poly-dopamine.
AB  - An electrochemical immunosensor was studied for sensitive detection of
      Interleukin-6 (IL-6) based on a dual amplification mechanism resulting from Au
      nanoparticles (AuNP)-Poly-dopamine (PDOP) as the sensor platform and multienzyme
      antibody functionalized AuNP-PDOP@carbon nanotubes (CNT). The stable and robust
      film, PDOP, was used to immobilize biomolecules not only for the construction of
      the sensor platform, but also for the signal labeling. Sensitivity was greatly
      amplified by using the special platform of AuNP-PDOP and synthesizing horseradish
      peroxidase (HRP)-antibody (Ab(2)) functionalized AuNP-PDOP@carbon nanotubes
      (CNT). A linear response range of IL-6 from 4.0 to 8.0 * 10(2) pg mL(-1) with a
      low detection limit of 1.0 pg mL(-1) was obtained by the amperometry
      determination. Measurements of IL-6 in human serum gave excellent correlations
      with standard ELISA assays. Moreover, the immunosensor exhibited high
      selectivity, good reproducibility, and stability.

PMID- 21174425
TI  - Boojum and stripe textures in long-range orientationally ordered monolayers on
      solid substrates.
AB  - Long-range organization of molecular tilt azimuth is a striking feature in
      monolayers at the air-water interface. We show that the boojum and stripe
      textures of pentadecanoic acid (PDA) with the continuous variations of molecular
      tilt azimuth formed at the air-water interface at temperatures lower than room
      temperature can be preserved after being transferred to glass substrates at low
      dipping speeds. The long-range tilt order in the transferred boojums and stripes
      is resolved by frictional force microscopy at room temperature, suggesting that
      the tilt order is "frozen" through the interaction of PDA molecules with the
      glass surface. The transferred stripe structure can be used as a unique alignment
      layer to induce a continuously azimuthal orientation of nematic liquid crystals.

PMID- 21174426
TI  - Langmuir and Gibbs magnetite NP layers at the air/water interface.
AB  - The interfacial properties of Fe(3)O(4)@MEO(2)MA(90)-co-OEGMA(10) NPs, recently
      developed and described as promising nanotools for biomedical applications, have
      been investigated at the air/water interface. These Fe(3)O(4) NPs, capped with
      catechol-terminated random copolymer brushes of 2-(2-methoxyethoxy) ethyl
      methacrylate (MEO(2)MA) and oligo(ethylene glycol) methacrylate (OEGMA), with
      molar fractions of 90% and 10%, respectively, proved to be surface active.
      Surface tension measurements of aqueous dispersions of the NPs showed that the
      adsorption of the NPs at the air/water interface is time- and concentration
      dependent. These NPs do not behave as classical amphiphiles. Once adsorbed at the
      air/water interface, they do not exchange with NPs in bulk, but they are trapped
      at the interface. This means that all NPs from the bulk adsorb to the interface
      until reaching maximum coverage of the interface, which corresponds to values
      between 6 * 10(-4) and 8 * 10(-4) mg/cm(2) and a critical equilibrium surface
      tension of ~47 mN/m. Moreover, Langmuir layers of Fe(3)O(4)@MEO(2)MA(90)-co
      OEGMA(10) NPs have been investigated by measuring surface pressure-area
      compression-expansion isotherms and in situ X-ray fluorescence spectra. The
      compression-expansion isotherms showed a plateau region above a critical surface
      pressure of ~25 mN/m and a pronounced hysteresis. By using a special one-barrier
      Langmuir trough equipped with two surface pressure microbalances, we have shown
      that the NPs are squeezed out from the interface into the aqueous subphase, and
      they readsorb on the other side of the barrier. The results have been supported
      by TEM as well as AFM experiments of transferred Langmuir-Schaefer films on solid
      supports. This study shows the ability of Fe(3)O(4)@MEO(2)MA(90)-co-OEGMA(10) NPs
      to transfer from hydrophilic media (an aqueous solution) to the
      hydrophobic/hydrophilic interface (air/water interface) and back to the
      hydrophilic media. This behavior is very promising, opening studies of their
      ability to cross biological membranes.

PMID- 21174427
TI  - On surface-initiated atom transfer radical polymerization using diazonium
      chemistry to introduce the initiator layer.
AB  - This work features the controllability of surface-initiated atom transfer radical
      polymerization (SI-ATRP) of methyl methacrylate, initiated by a multilayered 2
      bromoisobutyryl moiety formed via diazonium chemistry. The thickness as a
      function of polymerization time has been studied by varying different parameters
      such as the bromine content of the initiator layer, polarity of reaction medium,
      ligand type (L), and the ratio of activator (Cu(I)) to deactivator (Cu(II)) in
      order to ascertain the controllability of the SI-ATRP process. The variation of
      thickness versus surface concentration of bromine shows a gradual transition from
      mushroom to brush-type conformation of the surface anchored chains in both polar
      and nonpolar reaction medium. Interestingly, it is revealed that very thick
      polymer brushes, on the order of 1 MUm, can be obtained at high bromine content
      of the initiator layer in toluene. The initial polymerization rate and the
      overall final thickness are higher in the case of nonpolar solvent (toluene)
      compared to polar medium (acetonitrile or N,N-dimethylformamide). The ligand
      affects the initial rate of polymerization, which correlates with the redox
      potentials of the pertinent Cu(II)/Cu(I) complexes (L = Me(6)TREN, PMDETA, and
      BIPY). It is also observed that the ability of polymer brushes to reinitiate
      depends on the initial thickness and the solvent used for generating it.

PMID- 21174429
TI  - Fluorinated heterometallic beta-diketonates as volatile single-source precursors
      for the synthesis of low-valent mixed-metal fluorides.
AB  - Hexafluoroacetylacetonates that contain lead and divalent first-row transition
      metals, PbM(hfac)(4) (M = Ni (1), Co (2), Mn (3), Fe (4), and Zn (5)), have been
      synthesized. Their heterometallic structures are held together by strong Lewis
      acid-base interactions between metal atoms and diketonate ligands acting in
      chelating-bridging fashion. Compounds 1-5 are highly volatile and decompose below
      350  degrees C. Fluorinated heterometallic beta-diketonates have been used for
      the first time as volatile single-source precursors for the preparation of mixed
      metal fluorides. Complex fluorides of composition Pb(2)MF(6) have been obtained
      by decomposition of 1-5 in a two-zone furnace under low-pressure nitrogen flow.
      Lead-transition metal fluorides conform to orthorhombically distorted Aurivillius
      type structure with layers of corner-sharing [MF(6)] octahedra separated by alpha
      PbO-type (Pb(2)F(2)) blocks. Pb(2)NiF(6) and Pb(2)CoF(6) were found to exhibit
      magnetic ordering below 80 and 43 K, respectively. The ordering is
      antiferromagnetic, with a weak, uncompensated moment due to the canting of spins.
      The Pb(2)MF(6) fluorides represent a new class of prospective magnetoelectric
      materials combining transition metals and lone-pair main-group cations.

PMID- 21174428
TI  - Pd(II)-mediated assembly of porphyrin channels in bilayer membranes.
AB  - A membrane-spanning bis(meso-3-pyridyl) porphyrin 1 has been synthesized,
      embedded in EYPC vesicles, and upon Pd(II) addition has been shown to form
      ionophores that allow the passage of anionic 5/6-carboxyfluorescein through
      membranes. The geometric matching of bis(meso-3-pyridyl) porphyrin 1 and trans
      Pd(II) was designed to give a cyclic porphyrin trimer [PdCl(2)(1)](3). However,
      solution-phase studies showed that PdCl(2)(PhCN)(2) cross linked 1 into linear
      oligomers at porphyrin concentrations above 10 mM, although the formation of
      cyclic species was inferred from studies at concentrations below 2 MUM.
      Fluorescence titrations showed that embedding porphyrin 1 in bilayers greatly
      reduced its affinity for Pd(II), but the combination of porphyrin 1 and Pd(II)
      gave an ionophoric species that increased the rate of 5/6-carboxyfluorescein (5/6
      CF) transit through the phospholipid bilayer 12-fold. A maximum in the 5/6-CF
      release rate was observed at a Pd(II) concentration of 4 MUM, and the application
      of a solution-phase binding model to the membrane phase showed that this peak in
      ionophoric activity corresponded to the greatest extent of porphyrin
      oligomerization. Further studies suggested these Pd(II)/porphyrin oligomers
      transported 5/6-CF via a channel mechanism.

PMID- 21174430
TI  - Light-induced selective deposition of metals on gold-tipped CdSe-seeded CdS
      nanorods.
AB  - We introduce a facile approach for the selective deposition of metals on Au
      tipped CdSe-seeded CdS nanorods that exploits the transfer of electrons from CdS
      to the Au tips upon UV excitation. This light-induced deposition method was used
      for the deposition of Pd under mild conditions, which produced a Pd/Au alloyed
      tip while preserving the rest of the semiconductor nanoarchitecture. The highly
      site-selective deposition method was extended to the deposition of Fe, yielding
      monodispersed, structurally complex Au core/Fe(x)O(y) hollow shell-tipped
      semiconductor nanorods. These structurally well-defined rods were found to
      exhibit magnetic functionality. The synthetic strategies described in this work
      expand on the range of metals that can be deposited on heterostructured
      semiconductor nanorods, opening up new avenues for the hierarchical buildup of
      structural complexity and therefore multifunctionality in nanoparticles.

PMID- 21174431
TI  - Enhanced CO2 binding affinity of a high-uptake rht-type metal-organic framework
      decorated with acylamide groups.
AB  - An rht-type metal-organic framework (MOF) prepared from M(2)(carboxylate)(4) (M =
      Cu, Co) paddlewheel clusters and a flexible C(3)-symmetric hexacarboxylate ligand
      with acylamide groups exhibits larger CO(2) uptake, an enhanced heat of
      adsorption, and higher selectivity toward CO(2)/N(2) in comparison with what was
      previously observed for an analogous MOF with alkyne groups.

PMID- 21174432
TI  - Substituent effects on the assembly of helical cyanine dye aggregates in the
      minor groove of a DNA template.
AB  - Double-helical DNA was used as a template for the assembly of helical cyanine dye
      aggregates. The aggregates consist of cofacial dimers aligned end-to-end in the
      minor groove of the DNA. The effect of methoxy or fluoro substituents placed on
      the periphery of the cyanine dye heterocycles on aggregation both in water and on
      the DNA template was studied by UV-vis and circular dichroism spectroscopy.
      Methoxy groups were found to be stronger promoters of aggregation than fluoro,
      and a dimethoxy dye exhibited a higher propensity to aggregate compared with an
      unsymmetrical methoxy/fluoro dye. Semiempirical calculations supported the
      experimental observation of methoxy substitution favoring aggregation. These
      results indicate that dispersion and hydrophobic effects contribute more to
      dimerization/aggregation than do electron donor-acceptor effects.

PMID- 21174433
TI  - Cross-linking evidence for motional constraints within chemoreceptor trimers of
      dimers.
AB  - Chemotactic behavior in bacteria relies on the sensing ability of large
      chemoreceptor clusters that are usually located at the cell pole. In Escherichia
      coli, chemoreceptors exhibit higher-order interactions within those clusters
      based on a trimer-of-dimers organization. This architecture is conserved in a
      variety of other bacteria and archaea, implying that receptors in many
      microorganisms form trimer-of-dimer signaling teams. To gain further insight into
      the assembly and dynamic behavior of receptor trimers of dimers, we used in vivo
      cross-linking targeted to cysteine residues at various positions that define six
      different levels along the cytoplasmic signaling domains of the aspartate and
      serine chemoreceptors, Tar and Tsr, respectively. We found that the cytoplasmic
      domains of these receptors are close to each other near the trimer contact region
      at the cytoplasmic tip and lie farther apart as the receptor dimers approach the
      cytoplasmic membrane. Tar and Tsr reporter sites within the same or closely
      adjacent levels readily formed mixed cross-links, whereas reporters located
      different distances from the tip did not. These findings indicate that there are
      no significant vertical displacements of one dimer with respect to the others
      within the trimer unit. Attractant stimuli had no discernible effect on the cross
      linking efficiency of any of the reporters tested, but a strong osmotic stimulus
      reproducibly enhanced cross-linking at most of the reporter sites, indicating
      that individual dimers may move closer together under this condition.

PMID- 21174434
TI  - Discovery and SAR of 5-(3-chlorophenylamino)benzo[c][2,6]naphthyridine-8
      carboxylic acid (CX-4945), the first clinical stage inhibitor of protein kinase
      CK2 for the treatment of cancer.
AB  - Herein we chronicle the discovery of CX-4945 (25n), a first-in-class, orally
      bioavailable ATP-competitive inhibitor of protein kinase CK2 in clinical trials
      for cancer. CK2 has long been considered a prime cancer drug target because of
      the roles of deregulated and overexpressed CK2 in cancer-promoting prosurvival
      and antiapoptotic pathways. These biological properties as well as the
      suitability of CK2's small ATP binding site for the design of selective
      inhibitors, led us to fashion novel therapeutic agents for cancer. The
      optimization leading to 25n (K(i) = 0.38 nM) was guided by molecular modeling,
      suggesting a strong binding of 25n resulting from a combination of hydrophobic
      interactions, an ionic bridge with Lys68, and hydrogen bonding with the hinge
      region. 25n was found to be highly selective, orally bioavailable across species
      (20-51%) and efficacious in xenograft models. The discovery of 25n will allow the
      therapeutic targeting of CK2 in humans for the first time.

PMID- 21174436
TI  - Study of water adsorption on organics crystal surfaces using a modified X-ray
      photoelectron spectroscopy instrument.
AB  - The coupling of a high partial pressure water vapor system to a conventional X
      ray photoelectron spectroscopy instrument for use with both organic powders and
      single crystals is described. The modified chamber serves a dual purpose as both
      a treatment and sample preparation apparatus. The design utilizes the high- and
      cryo-temperature capabilities of the existing system to allow investigation of
      various states of surface water, as well as the interplay between temperature,
      water, and surface structure of the substrate. Sample handling and methods for
      compatibility testing are detailed, and data illustrating the application of the
      modified and integrated capabilities are summarized, detailing novel studies on
      the state of water on the surface of model organic pharmaceutical salts. In
      addition to facilitating investigation of the presence of various states of water
      at the surface of organic material, namely, dissociated versus molecular water,
      the setup allows the investigation of structural effects of the surface on the
      state of water.

PMID- 21174437
TI  - Detection of explosives and related compounds by low-temperature plasma ambient
      ionization mass spectrometry.
AB  - Detection of explosives is important for public safety. A recently developed low
      temperature plasma (LTP) probe for desorption and ionization of samples in the
      ambient environment ( Anal. Chem. 2008 , 80 , 9097 ) is applied in a
      comprehensive evaluation of analytical performance for rapid detection of 13
      explosives and explosives-related compounds. The selected chemicals
      [pentaerythritol tetranitrate (PETN), trinitrotoluene (TNT), cyclo-1,3,5
      trimethylenetrinitramine (RDX), tetryl, cyclo-1,3,5,7-tetramethylenetetranitrate
      (HMX), hexamethylene triperoxide diamine (HMTD), 2,4-dinitrotoluene, 1,3
      dinitrobenzene, 1,3,5-trinitrobenzene, 2-amino-4,6-dinitrotoluene, 4-amino-2,6
      dinitrotoluene, 2,6-dinitrotoluene, and 4-nitrotoluene) were tested at levels in
      the range 1 pg-10 ng. Most showed remarkable sensitivity in the negative-ion
      mode, yielding limits of detection in the low picogram range, particularly when
      analyzed from a glass substrate heated to 120  degrees C. Ions typically formed
      from these molecules (M) by LTP include [M + NO(2)](-), [M](-), and [M - NO(2)](
      ). The LTP-mass spectrometry methodology displayed a linear signal response over
      three orders of magnitude of analyte amount for the studied explosives. In
      addition, the effects of synthetic matrices and different types of surfaces were
      evaluated. The data obtained demonstrate that LTP-MS allows detection of
      ultratrace amounts of explosives and confirmation of their identity. Tandem mass
      spectrometry (MS/MS) was used to confirm the presence of selected explosives at
      low levels; for example, TNT was confirmed at absolute levels as low as 0.6 pg.
      Linearity and intra- and interday precision were also evaluated, yielding results
      that demonstrate the potential usefulness and ruggedness of LTP-MS for the
      detection of explosives of different classes. The use of ion/molecule reactions
      to form adducts with particular explosives such as RDX and HMX was shown to
      enhance the selectivity and specificity. This was accomplished by merging the
      discharge gas with an appropriate reagent headspace vapor (e.g., from a 0.2%
      trifluoracetic acid solution).

PMID- 21174438
TI  - Local and bulk hydration of zwitterionic glycine and its analogues through
      molecular simulations.
AB  - Molecular dynamics simulations were used to characterize the differences in
      hydration between glycine and two of its zwitterionic analogues: N,N
      dimethylglycine and N,N,N-trimethylglycine (glycine betaine). The hydration of
      dodecane and oligo(ethylene glycol) was studied for reference. Both structuring
      and dynamics of bulk and bound water were examined using a variety of properties
      and at multiple concentrations. Metrics, such as radial distribution functions
      and residence times, were used to characterize hydration. Also, we used more
      specialized metrics that can discriminate between subtle differences in
      hydration, such as condensed phase order parameters, Voronoi tessellations, and
      multidimensional pair-pair correlation functions. Trimethylglycine was found to
      have a unique hydration shell that extends across the entire molecule and has no
      specific interactions between solute molecules. Also, we found that
      dimethylglycine has a similar hydration structure to that of trimethylglycine
      despite its hydrogen-bond donor. Glycine was found to aggregate and have a more
      disjoint hydration shell. All three zwitterions were found to structurally affect
      water within 1.5-2.0 coordination shells. Lastly, trimethylglycine is disperse in
      solution even at very high concentrations, and water rapidly moves between
      trimethylglycine amine groups. This work has meaningful implications for protein
      stability where trimethylglycine is known to prevent protein aggregation and
      nonfouling interfaces where trimethylglycine prevents nonspecific protein
      adsorption.

PMID- 21174439
TI  - Self-localizing stabilized mega-pixel picoliter arrays with size-exclusion
      sorting capabilities.
AB  - We report on a liquid self-localizing process capable of producing Mega-pixel
      arrays of picoliter volumes on a 1 cm(2) area, within seconds, for high
      throughput sampling. The chip is based on principles of spatially varying wetting
      and stabilization. The key is to develop differential surface contact regions,
      which lead to both localization of the solution and increasing the surface
      adsorption energy to further pin the liquid to the surface, as highlighted by
      other studies. By exploiting surface roughness for enhanced wettability, we
      demonstrate wetting of wells with the aspect ratio of 100. The high precision of
      reactive ion etching (RIE) of silicon substrates allows for an extremely
      reproducible method of preparing the array of identical well structures and
      increased contact area to increase surface adsorption in the wells. "Dynamic
      wetting" is then readily achieved through inducing contact line instability by
      simply moving a drop of liquid on the top surface of the array. Liquid samples
      self-localize into the array pattern with the associated liquid flow leading to
      self-localization of suspended particles or analyte. The resulting picoliter
      volumes are both spatially ordered and stable for long periods of time, even for
      such small volumes, to permit selective measurements of the contents. This
      development will be particularly important in the assembly of the massive amounts
      of crystalline particles needed for atomically resolved structural dynamics using
      the latest advances in high number density electron and X-ray sources.

PMID- 21174441
TI  - pH-controlled photoinduced electron transfer in the [(Mo6Cl8)L6]
      calix[4]resorcine-dimethylviologen system.
AB  - A pH-controlled photoinduced electron transfer in the supramolecular system
      [(Mo(6)Cl(8))L(6)]-calix[4]resorcine-dimethylviologen is reported.

PMID- 21174440
TI  - P3HT/PCBM bulk heterojunction organic photovoltaics: correlating efficiency and
      morphology.
AB  - Controlling thin film morphology is key in optimizing the efficiency of polymer
      based photovoltaic (PV) devices. We show that morphology and interfacial behavior
      of the multicomponent active layers confined between electrodes are strongly
      influenced by the preparation conditions. Here, we provide detailed descriptions
      of the morphologies and interfacial behavior in thin film mixtures of
      regioregular poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl C61-butyric acid
      methyl ester (PCBM), a typical active layer in a polymer-based PV device, in
      contact with an anode layer of PEDOT-PSS and either unconfined or confined by an
      Al cathode during thermal treatment. Small angle neutron scattering and electron
      microscopy show that a nanoscopic, bicontinuous morphology develops within
      seconds of annealing at 150  degrees C and coarsens slightly with further
      annealing. P3HT and PCBM are shown to be highly miscible, to exhibit a rapid,
      unusual interdiffusion, and to display a preferential segregation of one
      component to the electrode interfaces. The ultimate morphology is related to
      device efficiency.

PMID- 21174435
TI  - Peptide signaling in the staphylococci.

PMID- 21174442
TI  - Asymmetric synthesis of both mirror images of 3'-fluorothalidomide by
      enantiodivergent fluorination using a single, cinchona alkaloid.
AB  - Enantiomerically pure 3'-fluorothalidomide (2) was successfully synthesized by
      enantiodivergent electrophilic fluorination using a combination of cinchona
      alkaloids and N-fluorobenzenesulfonimide (NFSI) as the key reaction. Importantly,
      a single chiral molecule, dihydroquinine (DHQ), allowed access to the mirror
      image form of 3'-fluorothalidimide by the choice of additives. While the use of
      TMEDA gave fluorinated (S)-4, the precursor of 2, with 78% ee, Cu(acac)(2)/bipy,
      afforded the antipode, (R)-4, in 77% ee.

PMID- 21174444
TI  - Microwave, high-resolution infrared, and quantum chemical investigations of
      CHBrF2: ground and v4 = 1 states.
AB  - A combined microwave, infrared, and computational investigation of CHBrF(2) is
      reported. For the vibrational ground state, measurements in the millimeter- and
      sub-millimeter-wave regions for CH(79)BrF(2) and CH(81)BrF(2) provided rotational
      and centrifugal-distortion constants up to the sextic terms as well as the
      hyperfine parameters (quadrupole-coupling and spin-rotation interaction
      constants) of the bromine nucleus. The determination of the latter was made
      possible by recording of spectra at sub-Doppler resolution, achieved by means of
      the Lamb-dip technique, and supporting the spectra analysis by high-level quantum
      chemical calculations at the coupled-cluster level. In this context, the
      importance of relativistic effects, which are of the order of 6.5% and included
      in the present work using second-order direct perturbation theory, needs to be
      emphasized for accurate predictions of the bromine quadrupole-coupling constants.
      The infrared measurements focused on the nu(4) fundamental band of CH(79)BrF(2).
      Fourier transform investigations using a synchrotron radiation source provided
      the necessary resolution for the observation and analysis of the rotational
      structure. The spectroscopic parameters of the v(4) = 1 state were found to be
      close to those of the vibrational ground state, indicating that the nu(4) band is
      essentially unaffected by perturbations.

PMID- 21174443
TI  - Unique dynamic properties of DNA duplexes containing interstrand cross-links.
AB  - Bifunctional DNA alkylating agents form a diverse assortment of covalent DNA
      interstrand cross-linked (ICL) structures that are potent cytotoxins. Because it
      is implausible that cells could possess distinct DNA repair systems for each
      individual ICL, it is believed that common structural and dynamic features of ICL
      damage are recognized, rather than specific structural characteristics of each
      cross-linking agent. Investigation of the structural and dynamic properties of
      ICLs that might be important for recognition has been complicated by
      heterogeneous incorporation of these lesions into DNA. To address this problem,
      we have synthesized and characterized several homogeneous ICL DNAs containing
      site-specific staggered N4-cytosine-ethyl-N4-cytosine cross-links. Staggered
      cross-links were introduced in two ways, in a manner that preserves the overall
      structure of B-form duplex DNA and in a manner that highly distorts the DNA
      structure, with the goal of understanding how structural and dynamic properties
      of diverse ICL duplexes might flag these sites for repair. Measurements of base
      pair opening dynamics in the B-form ICL duplex by (1)H NMR line width or imino
      proton solvent exchange showed that the guanine base opposite the cross-linked
      cytosine opened at least 1 order of magnitude more slowly than when in a control
      matched normal duplex. To a lesser degree, the B-form ICL also induced a decrease
      in base pair opening dynamics that extended from the site of the cross-link to
      adjacent base pairs. In contrast, the non-B-form ICL showed extensive
      conformational dynamics at the site of the cross-link, which extended over the
      entire DNA sequence. Because DNA duplexes containing the B-form and non-B-form
      ICL cross-links have both been shown to be incised when incubated in mammalian
      whole cell extracts, while a matched normal duplex is not, we conclude that
      intrinsic DNA dynamics is not a requirement for specific damage incision of these
      ICLs. Instead, we propose a general model in which destabilized ICL duplexes
      serve to energetically facilitate binding of DNA repair factors that must induce
      bubbles or other distortions in the duplex. However, the essential requirement
      for incision is an immobile Y-junction where the repair factors are stably bound
      at the site of the ICL, and the two DNA strands are unpaired.

PMID- 21174445
TI  - Improved hydration-sensitive dual-fluorescence labels for monitoring peptide
      nucleic acid interactions.
AB  - Environmentally sensitive labels constitute a new, attractive tool for monitoring
      biomolecular interactions. 3-Hydroxychromone derivatives are of particular
      interest because they undergo excited-state intramolecular proton transfer
      (ESIPT) showing dual emission highly sensitive to environmental hydration. To
      overcome the drawbacks of the previously developed label for sensing protein-DNA
      interactions based on 2-furanyl-3-hydroxychromone (FC), a series of hydration
      sensitive labels based on 3-hydroxy-4'-methoxyflavone have been synthesized. As
      compared to FC, the new labels display higher sensitivity of the ratio of their
      two emission bands (N*/T*) to solvent polarity and H-bond donor ability, as well
      as higher fluorescence quantum yields in water. Moreover, they show higher pK(a)
      values of their 3-hydroxyl group, allowing their application at neutral pH
      without interference of anionic forms. To illustrate the applications of these
      labels, we covalently coupled them to the N-terminus of the Tat(44-61) peptide
      that corresponds to the basic domain of the HIV-1 Tat protein. This coupling did
      not modify the nucleic acid chaperone properties of the peptide. Binding of
      oligonucleotides of varying length, sequence, and strandedness to the labeled
      peptides induced dramatic change in the N*/T* ratio of their two emission bands.
      This change indicated that the level of probe hydration in the
      peptide/oligonucleotide complexes decreases in the following order: short ssDNAs
      ? long ssDNAs > DNA hairpins > dsDNAs. The level of probe hydration was related
      to the ability of the probe to stack with the DNA bases or base pairs in the
      various complexes. The changes in the N*/T* ratio upon interaction of the labeled
      Tat peptides with DNA were about 3-fold larger with the new probes as compared to
      the parent FC label, in line with the higher sensitivity of the new probes to the
      environment. One of these labels, presenting the most compact geometry, showed
      the highest sensitivity, probably due to its optimal stacking with the DNA bases.
      Thus, the new hydration-sensitive labels appear as improved highly sensitive
      tools to site-selectively monitor the binding of peptides to oligonucleotides and
      nucleic acids.

PMID- 21174446
TI  - Dnmt3a-CD is less susceptible to bulky benzo[a]pyrene diol epoxide-derived DNA
      lesions than prokaryotic DNA methyltransferases.
AB  - Benzo[a]pyrene (B[a]P) is a well-characterized environmental polycyclic aromatic
      hydrocarbon pollutant. In living organisms, B[a]P is metabolized to the genotoxic
      anti-benzo[a]pyrene diol epoxide that reacts with cellular DNA to form
      stereoisomeric anti-B[a]PDE-N(2)-dG adducts. In this study, we explored the
      effects of adduct stereochemistry and position in double-stranded DNA substrates
      on the functional characteristics of the catalytic domain of murine de novo DNA
      methyltransferase Dnmt3a (Dnmt3a-CD). A number of 18-mer duplexes containing site
      specifically incorporated (+)- and (-)-trans-anti-B[a]PDE-N(2)-dG lesions located
      3'- and 5'-adjacent to and opposite the target cytosine residue were prepared.
      Dnmt3a-CD binds cooperatively to the DNA duplexes with an up to 5-fold greater
      affinity compared to that for the undamaged DNA duplexes. Methylation assays
      showed a 1.7-6.3-fold decrease in the methylation reaction rates for the damaged
      duplexes. B[a]PDE modifications stimulated a nonproductive binding and markedly
      favored substrate inhibition of Dnmt3a-CD in a manner independent of DNA
      methylation status. The latter effect was sensitive to the position and
      stereochemistry of the B[a]PDE-N(2)-dG adducts. The overall effect of trans-anti
      B[a]PDE-N(2)-dG adducts on Dnmt3a-CD was less detrimental than in the case of the
      prokaryotic methyltransferases we previously investigated.

PMID- 21174447
TI  - Enhanced specificity against misfolding in a thermostable mutant of the
      Tetrahymena ribozyme.
AB  - Structured RNAs encode native conformations that are more stable than the vast
      ensembles of alternative conformations, but how this specificity is evolved is
      incompletely understood. Here we show that a variant of the Tetrahymena group I
      intron ribozyme that was generated previously by in vitro selection for enhanced
      thermostability also displays modestly enhanced specificity against a stable
      misfolded structure that is globally similar to the native state, despite the
      absence of selective pressure to increase the energy gap between these
      structures. The enhanced specificity for native folding arises from mutations in
      two nucleotides that are close together in space in the native structure, and
      additional experiments show that these two mutations do not affect the stability
      of the misfolded conformation relative to the largely unstructured transition
      state ensemble for interconversion between the native and misfolded conformers.
      Thus, they selectively stabilize the native state, presumably by strengthening a
      local tertiary contact network that cannot form in the misfolded conformation.
      The stabilization is larger in the presence of the peripheral element P5abc,
      suggesting that cooperative tertiary structure formation plays a key role in the
      enhanced stability. The increased specificity in the absence of explicit
      selection suggests that the large energy gap in the wild-type RNA may have arisen
      analogously, a consequence of selective pressure for stability of the functional
      structure. More generally, the structural rigidity and intricate networks of
      contacts in structured RNAs may allow them to evolve substantial structural
      specificity without explicit negative selection, even against closely related
      alternative structures.

PMID- 21174449
TI  - A new dimeric iridal triterpenoid from Belamcanda chinensis with significant
      molluscicide activity.
AB  - An unprecedented dimeric triterpenoid, designated dibelamcandal A, with a six
      membered ring linking two iridal type triterpenoid nuclei, was isolated from the
      rhizome of Belamcanda chinensis. Its structure was determined by extensive
      spectroscopic measurements, including IR, ESI-MS, HR-ESI-MS, and 1D and 2D NMR.
      It demonstrated significant molluscicide activity against Pomacea canaliculata.

PMID- 21174450
TI  - Spectral shift of the n -> pi* transition for acetone and formic acid with an
      explicit solvent model.
AB  - In our recent work, a new form of the electrostatic solvation energy for the
      nonequilibrium polarization has been derived by introducing the method of
      constrained equilibrium state in the framework of continuous medium theory. Up
      until now, the idea of the constrained equilibrium state method has not been
      introduced into the explicit solvent model by others; therefore this
      nonequilibrium energy form was further equivalently extended to the explicit
      solvent model in this work based on the discrete representation of the solvent
      permanent charges and induced dipoles. Making use of this expression in explicit
      solvent model, we modified the nonequilibrium module in the averaged solvent
      electrostatic potential/molecular dynamics program to implement numerical
      calculations. Subsequently, the new codes were applied to study the
      solvatochromic shifts of the n -> pi* absorption spectra for acetone and trans
      formic acid in aqueous solution. The calculation results show a good agreement
      with the experimental observations. When our results of spectral shift are
      compared with those achieved directly from the continuum model, it can be seen
      that both the explicit solvent model and continuum model derived based on the
      constrained equilibrium approach can give reasonable predictions. The hydrogen
      bond effect was also discussed and deemed to be a dominant contribution to the
      spectral shift by calculating the n -> pi* absorption spectra of acetone-water
      complexes.

PMID- 21174448
TI  - Structure of a slow CLC Cl-/H+ antiporter from a cyanobacterium.
AB  - X-ray crystal structures have been previously determined for three CLC-type
      transporter homologues, but the absolute unitary transport rate is known for only
      one of these. The Escherichia coli Cl(-)/H(+) antiporter (EC) moves ~2000 Cl(-)
      ions/s, an exceptionally high rate among membrane-transport proteins. It is not
      known whether such rapid turnover is characteristic of ClCs in general or if the
      E. coli homologue represents a functional outlier. Here, we characterize a CLC
      Cl(-)/H(+) antiporter from the cyanobacterium Synechocystis sp. PCC6803 (SY) and
      determine its crystal structure at 3.2 A resolution. The structure of SY is
      nearly identical to that of EC, with all residues involved in Cl(-) binding and
      proton coupling structurally similar to their equivalents in EC. SY actively
      pumps protons into liposomes against a gradient and moves Cl(-) at ~20 s(-1), 1%
      of the EC rate. Electrostatic calculations, used to identify residues
      contributing to ion binding energetics in SY and EC, highlight two residues
      flanking the external binding site that are destabilizing for Cl(-) binding in SY
      and stabilizing in EC. Mutation of these two residues in SY to their counterparts
      in EC accelerates transport to ~150 s(-1), allowing measurement of Cl(-)/H(+)
      stoichiometry of 2/1. SY thus shares a similar structure and a common transport
      mechanism to EC, but it is by comparison slow, a result that refutes the idea
      that the transport mechanism of CLCs leads to intrinsically high rates.

PMID- 21174451
TI  - GaAs-based nanoneedle light emitting diode and avalanche photodiode
      monolithically integrated on a silicon substrate.
AB  - Monolithic integration of III-V compound semiconductor devices with silicon CMOS
      integrated circuits has been hindered by large lattice mismatches and
      incompatible processing due to high III-V epitaxy temperatures. We report the
      first GaAs-based avalanche photodiodes (APDs) and light emitting diodes, directly
      grown on silicon at a very low, CMOS-compatible temperature and fabricated using
      conventional microfabrication techniques. The APDs exhibit an extraordinarily
      large multiplication factor at low voltage resulting from the unique needle shape
      and growth mode.

PMID- 21174452
TI  - Computational screening and design of DNA-linked molecular nanowires.
AB  - DNA can be used as a structural component in the process of making conductive
      polymers called nanowires. Accurate molecular models could lead to a better
      understanding of how to prepare these types of materials. Here we present a
      computational tool that allows potential DNA-linked polymer designs to be
      screened and evaluated. The approach involves an iterative procedure that adjusts
      the positions of DNA-linked monomers in order to obtain reasonable molecular
      geometry compatible with normal DNA conformations and with the properties of the
      polymer being formed. This procedure has been used to evaluate designs already
      reported experimentally, as well as to suggest a new design based on pyrrylene
      vinylene (PV) monomers.

PMID- 21174453
TI  - New bioinspired membrane made of a biological ion channel confined into the
      cylindrical nanopore of a solid-state polymer.
AB  - A hybrid nanoporous membrane made of a solid-state polymeric thin film in which
      an ion channel is confined is realized. The primary and extremely encouraging
      results obtained by confocal fluorescence spectroscopy and ion diffusion
      measurement demonstrate respectively that (i) the considered ion channel, that
      is, Gramicidin-A, can be confined selectively inside the nanopores and (ii) the
      ionic permeability of the membrane is enhanced. Atomistic molecular simulations
      are also reported and fruitfully compared to the experimental findings.

PMID- 21174454
TI  - Formation of PCDD/Fs from the copper oxide-mediated pyrolysis and oxidation of
      1,2-dichlorobenzene.
AB  - Formation of polychorinated dibenzo-p-dioxins (PCDDs) has been demonstrated to
      occur via surface-mediated reactions of chlorinated phenols. However,
      polychlorinated dibenzofurans (PCDFs) are observed in much lower yields in
      laboratory studies than in full-scale combustors where PCDFs are in higher
      concentrations than PCDDs. This has led to the suggestion that at least PCDFs are
      formed from elemental carbon in the de novo process. However, the potential for
      PCDF formation from reactions of chlorinated benzenes has been largely
      overlooked. In this study, we investigated the potential contribution of
      chlorinated benzenes to formation of PCDD/Fs using 1,2-dichlorobenzene as a
      surrogate for reactions of other chlorinated benzenes and CuO/silica (3 wt % Cu)
      as a surrogate for fly ash. Results were similar for oxidative and pyrolytic
      conditions with a slight increase in more chlorinated products under oxidative
      conditions. Reaction products included chlorobenzene, polychlorinated benzenes,
      phenol, 2-monochlorophenol (2-MCP), dichlorophenols, and trichlorophenols with
      yields ranging from 0.01 to 2% for the phenols and from 0.01 to 10% for
      chlorinated benzenes. 4,6-Dichlorodibenzo furan (4,6-DCDF) and dibenzofuran (DF)
      were observed in maximum yields of 0.2% and 0.5%, respectively, under pyrolytic
      conditions and 0.1% and 0.3%, respectively, under oxidative conditions. In
      previous studies of the pyrolysis of 2-MCP under identical conditions, 4,6-DCDF
      and dibenzo-p-dioxin (DD) were observed with maximum yields of ~0.2% and ~0.1%,
      respectively, along with trace quantities of 1-monochlorodibenzo-p-dioxin (1
      MCDD). Under oxidative conditions, 1-MCDD, DD, and 4,6-DCDF were observed with
      maximum yields of 0.3%, 0.07% and 0.1%, respectively. When combined with the fact
      that measured concentrations of chlorinated benzenes are 10-100* that of
      chlorinated phenols in full-scale combustion systems, the data suggest surface
      mediated reactions of chlorinated benzenes can be a significant source of PCDD/F
      emissions.

PMID- 21174455
TI  - Equilibrium sampling of persistent and bioaccumulative compounds in soil and
      sediment: comparison of two approaches to determine equilibrium partitioning
      concentrations in lipids.
AB  - The equilibrium sampling in silicone is increasingly applied to measure freely
      dissolved concentrations and chemical activities within bioaccumulation research
      of hydrophobic organic chemicals. Two equilibrium methods were applied to PCB
      contaminated soil and sediment, and directly calibrated with respect to
      equilibrium partitioning concentrations in lipids (C(lipid,partitioning)): (i)
      Solid phase microextraction in the headspace above the sample (HS-SPME) required
      optimization for its application to PCBs, and it was calibrated above external
      partitioning standards in olive oil. (ii) Equilibrium sampling with internally
      coated glass jars with varying thicknesses of silicone (PDMS) resulted in
      proportionality between coating and analyte mass, which confirmed several
      validity criteria. C(lipid,partitioning) was here determined as product of PDMS
      concentration and PDMS to lipid partition ratio. The results of the two methods
      were in good agreement and thus validated each other. Finally, the coated glass
      jar method was applied to field sediment containing invertebrates, which lead to
      C(lipid,partitioning) that were about two times higher than measured lipid
      normalized concentrations in the organisms. Temperature differences and animal
      lipid structure were discussed as possible reasons for this discrepancy. Both
      methods combine high analytical performance, reduced equilibration times and new
      calibration possibilities, which makes them suited for bioaccumulation research
      and environmental monitoring.

PMID- 21174456
TI  - Size-dependent bioavailability of hematite (alpha-Fe2O3) nanoparticles to a
      common aerobic bacterium.
AB  - The size-dependent bioavailability of hematite (alpha-Fe(2)O(3)) nanoparticles to
      obligate aerobic Pseudomonas mendocina bacteria was examined using the natural
      siderophore-producing wild type strain and a siderophore(-) mutant strain.
      Results showed that Fe from hematite less than a few tens of nm in size appears
      to be considerably more bioavailable than Fe associated with larger particles.
      This increased bioavailability is related to the total available particle surface
      area, and depends in part on greater accessibility of the Fe to the chelating
      siderophore(s). Greater bioavailability is also related to mechanism(s) that
      depend on cell/nanomineral proximity, but not on siderophores. Siderophore(-)
      bacteria readily acquire Fe from particles <10 nm but must be in direct physical
      proximity to the nanomineral; the bacteria neither produce a diffusible Fe
      mobilizing agent nor accumulate a reservoir of dissolved Fe in supernatant
      solutions. Particles <10 nm appear to be capable of penetrating the outer cell
      wall, offering at least one possible pathway for Fe acquisition. Other cell
      surface-associated molecules and/or processes could also be important, including
      a cell-wall associated reducing capability. The increased bioavailability of <10
      nm particles has implications for both biogeochemical Fe cycling and applications
      involving engineered nanoparticles, and raises new questions regarding biogenic
      influences on adsorbed contaminants.

PMID- 21174457
TI  - Volatilization of organotin species from municipal waste deposits: novel species
      identification and modeling of atmospheric stability.
AB  - Organotin compounds are used as pesticides and fungicides as well as additives in
      plastics. This study identifies the de novo generation of novel volatile
      organotins in municipal waste deposits and their release via landfill gas.
      Besides tetramethyltin (Me(4)Sn), a strong neurotoxin, and 5 previously reported
      organotins, 13 novel ethylated, propylated, and butylated tetraalkyltin compounds
      were identified. A concentration of 2-4 MUg of Sn m(-3) landfill gas was
      estimated for two landfill sites in Scotland. The atmospheric stability of
      Me(4)Sn and methylated tin hydrides was determined empirically in a static
      atmosphere in the dark and under UV light to simulate night- and daytime
      conditions. Theoretical calculations were carried out to help predict the
      experimentally obtained stabilities and to estimate the relative stabilities of
      other alkylated species. Assuming first-order kinetics, the atmospheric half-life
      for Me(3)SnH was found to be 33 +/- 16 and 1311 +/- 111 h during day- and
      nighttime conditions, respectively. Polyalkylation and larger alkyl substitutes
      tend to reduce the atmospheric stability. These results show that substantial
      concentrations of neurotoxic organotin compounds can be released from landfill
      sites and are sufficiently stable in the atmosphere to travel over large
      distances in night- and daytime conditions to populated areas.

PMID- 21174458
TI  - metaXCMS: second-order analysis of untargeted metabolomics data.
AB  - Mass spectrometry-based untargeted metabolomics often results in the observation
      of hundreds to thousands of features that are differentially regulated between
      sample classes. A major challenge in interpreting the data is distinguishing
      metabolites that are causally associated with the phenotype of interest from
      those that are unrelated but altered in downstream pathways as an effect. To
      facilitate this distinction, here we describe new software called metaXCMS for
      performing second-order ("meta") analysis of untargeted metabolomics data from
      multiple sample groups representing different models of the same phenotype. While
      the original version of XCMS was designed for the direct comparison of two sample
      groups, metaXCMS enables meta-analysis of an unlimited number of sample classes
      to facilitate prioritization of the data and increase the probability of
      identifying metabolites causally related to the phenotype of interest. metaXCMS
      is used to import XCMS results that are subsequently filtered, realigned, and
      ultimately compared to identify shared metabolites that are up- or down-regulated
      across all sample groups. We demonstrate the software's utility by identifying
      histamine as a metabolite that is commonly altered in three different models of
      pain. metaXCMS is freely available at http://metlin.scripps.edu/metaxcms/.

PMID- 21174459
TI  - Biosynthesis of 2-methylisoborneol in cyanobacteria.
AB  - The production of odiferous metabolites, such as 2-methlyisoborneol (MIB), is a
      major concern for water utilities worldwide. Although MIB has no known biological
      function, the presence of the earthy/musty taste and odor attributed to this
      compound result in the reporting of numerous complaints by consumers, which
      undermines water utility performance and the safe and adequate provision of
      potable waters. Cyanobacteria are the major producers of MIB in natural waters,
      by mechanisms that have heretofore remained largely unstudied. To investigate the
      fundamental biological mechanism of MIB biosynthesis in cyanobacteria, the genome
      of a MIB-producing Pseudanabaena limnetica was sequenced using Next Generation
      Sequencing, and the recombinant proteins derived from the putative MIB
      biosynthetic genes were biochemically characterized. We demonstrate that the
      biosynthesis of MIB in cyanobacteria is a result of 2 key reactions: 1) a S
      adenosylmethionine-dependent methylation of the monoterpene precursor geranyl
      diphosphate (GPP) to 2-methyl-GPP catalyzed by geranyl diphosphate 2
      methyltransferase (GPPMT) and 2) further cyclization of 2-methyl-GPP to MIB
      catalyzed by MIB synthase (MIBS) as part of a MIB operon. Based on a comparison
      of the component MIB biosynthetic genes in actinomycetes and cyanobacterial
      organisms, we hypothesize that there have been multiple rearrangements of the
      genes in this operon.

PMID- 21174460
TI  - Shewanella oneidensis MR-1 chemotaxis in a diffusion gradient chamber.
AB  - To obtain a systems-level understanding of Shewanella biology and ecology, the
      influence of electron acceptor availability on Shewanella's growth, metabolism,
      and transport needs to be elucidated. The diffusion gradient chamber (DGC) is an
      experimental tool developed to study population-level microbial growth and
      motility in response to concentration gradients. In this paper, the response of
      populations of Shewanella oneidensis MR-1 cells to an applied single gradient of
      the electron acceptor fumarate and applied opposing gradients of fumarate and
      nitrate, also an electron acceptor, were studied in the DGC. Mathematical models
      capable of predicting cellular growth and chemotaxis under the influence of
      gradients were used to analyze the results. Examining wild-type cells grown in a
      single gradient of fumarate, we found that MR-1 cells formed a chemotactic band
      that migrated up the electron acceptor gradient essentially as predicted by the
      model. The predicted velocity of the chemotactic cell band advancing toward the
      chemoattractant source (0.139 cm/h, R(2) = 0.996) closely matched that measured
      in the DGC (0.134 cm/h, R(2) = 0.997). Investigating the impact of opposing
      gradients of nitrate and fumarate on the chemotactic behaviors of S. oneidensis
      MR-1 fumarate reductase and nitrate reductase mutants, we found that the DGC was
      able to separate these mutants based upon their abilities to use the available
      electron acceptors in accordance with model predictions. Differences in the
      ability of Shewanella species to respond to and use available electron acceptors
      is thought to play an important role in their ecology. Therefore, these results
      validate the use of the DGC system to measure and simulate Shewanella chemotaxis
      in response to electron acceptor gradients and establish it as a research tool to
      help elucidate Shewanella's role in environmental processes.

PMID- 21174462
TI  - Externally applied electric fields up to 1.6 * 10(5) V/m do not affect the
      homogeneous nucleation of ice in supercooled water.
AB  - The freezing of water can initiate at electrically conducting electrodes kept at
      a high electric potential or at charged electrically insulating surfaces. The
      microscopic mechanisms of these phenomena are unknown, but they must involve
      interactions between water molecules and electric fields. This paper investigates
      the effect of uniform electric fields on the homogeneous nucleation of ice in
      supercooled water. Electric fields were applied across drops of water immersed in
      a perfluorinated liquid using a parallel-plate capacitor; the drops traveled in a
      microchannel and were supercooled until they froze due to the homogeneous
      nucleation of ice. The distribution of freezing temperatures of drops depended on
      the rate of nucleation of ice, and the sensitivity of measurements allowed
      detection of changes by a factor of 1.5 in the rate of nucleation. Sinusoidal
      alternation of the electric field at frequencies from 3 to 100 kHz prevented free
      ions present in water from screening the electric field in the bulk of drops.
      Uniform electric fields in water with amplitudes up to (1.6 +/- 0.4) * 10(5) V/m
      neither enhanced nor suppressed the homogeneous nucleation of ice. Estimations
      based on thermodynamic models suggest that fields in the range of 10(7)-10(8) V/m
      might cause an observable increase in the rate of nucleation.

PMID- 21174463
TI  - On the origin of the efficient nanoparticle mediated electron transfer across a
      self-assembled monolayer.
AB  - Recent advances in bioelectrochemistry came from the elaboration of conducting
      electrodes modified by an organic layer onto which nanoparticles are adsorbed.
      Self-assembled monolayers on noble-metal electrodes are known to hinder the
      electrochemical kinetics of fast-transfer redox systems. Surprisingly, fast
      kinetics are recovered when metal nanoparticles are deposited on top of the
      monolayer. We show that this surprising behavior can be fully accounted for when
      realizing that electron transfer from metal to metal is intrinsically easier than
      transfer between metal and redox system by many orders of magnitude.

PMID- 21174461
TI  - Atomistic folding simulations of the five-helix bundle protein lambda(6-85).
AB  - Protein folding is a classic grand challenge that is relevant to numerous human
      diseases, such as protein misfolding diseases like Alzheimer's disease. Solving
      the folding problem will ultimately require a combination of theory, simulation,
      and experiment, with theory and simulation providing an atomically detailed
      picture of both the thermodynamics and kinetics of folding and experimental tests
      grounding these models in reality. However, theory and simulation generally fall
      orders of magnitude short of biologically relevant time scales. Here we report
      significant progress toward closing this gap: an atomistic model of the folding
      of an 80-residue fragment of the lambda repressor protein with explicit solvent
      that captures dynamics on a 10 milliseconds time scale. In addition, we provide a
      number of predictions that warrant further experimental investigation. For
      example, our model's native state is a kinetic hub, and biexponential kinetics
      arises from the presence of many free-energy basins separated by barriers of
      different heights rather than a single low barrier along one reaction coordinate
      (the previously proposed incipient downhill folding scenario).

PMID- 21174464
TI  - Kinetics and mechanism of the glyoxal + HO2 reaction: conversion of HO2 to OH by
      carbonyls.
AB  - The kinetics of the glyoxal + HO(2) reaction have been investigated using
      computational chemistry and statistical reaction rate theory techniques, with
      consideration of a novel pathway that results in the conversion of HO(2) to OH.
      Glyoxal is shown to react with HO(2) to form an alpha-hydroxyperoxy radical with
      additional alpha-carbonyl functionality. Intramolecular H atom abstraction from
      the carbonyl moiety proceeds with a relatively low barrier, facilitating
      decomposition to OH + CO + HC(O)OH (formic acid). Time-dependent master equation
      simulations demonstrate that direct reaction to form OH is relatively slow at
      ambient temperature. The major reaction product is predicted to be collisionally
      deactivated HC(OH)(OO)CHO, which predominantly dissociates to reform the
      reactants under low-NO(x) conditions. The mechanism described here for the
      conversion of OH to HO(2) is available to a diverse range of carbonyls, including
      methylglyoxal, glycolaldehyde, hydroxyacetone, and glyoxylic acid, and energy
      surfaces are reported for the reaction of these species with HO(2).

PMID- 21174465
TI  - UPIOM: a new tool of MFA and its application to the flow of iron and steel
      associated with car production.
AB  - Identification of the flow of materials and substances associated with a product
      system provides useful information for Life Cycle Analysis (LCA), and contributes
      to extending the scope of complementarity between LCA and Materials Flow
      Analysis/Substances Flow Analysis (MFA/SFA), the two major tools of industrial
      ecology. This paper proposes a new methodology based on input-output analysis for
      identifying the physical input-output flow of individual materials that is
      associated with the production of a unit of given product, the unit physical
      input-output by materials (UPIOM). While the Sankey diagram has been a standard
      tool for the visualization of MFA/SFA, with an increase in the complexity of the
      flows under consideration, which will be the case when economy-wide intersectoral
      flows of materials are involved, the Sankey diagram may become too complex for
      effective visualization. An alternative way to visually represent material flows
      is proposed which makes use of triangulation of the flow matrix based on degrees
      of fabrication. The proposed methodology is applied to the flow of pig iron and
      iron and steel scrap that are associated with the production of a passenger car
      in Japan. Its usefulness to identify a specific MFA pattern from the original IO
      table is demonstrated.

PMID- 21174466
TI  - Nanoscale structure of the cell wall protecting cellulose from enzyme attack.
AB  - The cell wall structure protects cellulose from enzymatic attack and its
      successive fermentation. The nature of this protection consists in the very
      complex macroscopic and microscopic structure of cell wall that limits transport.
      Explaining this kind of protection is critical in future research to improve cell
      polymer availability for enzymatic attack. This research shows that the complete
      description of the cell wall topography at a nanoscale level allows a mechanistic
      understanding of cellulose protection. For this purpose, we used gas adsorption
      methods (CO(2) at 273 K and N(2) at 77 K) to detect mesoporosity (pore size of
      1.5-30 nm diameter; MeS) and microporosity (pore size of 0.3-1.5 nm diameter;
      MiS) of the cell wall of five energy crops, i.e., giant cane, rivet wheat straw,
      miscanthus, proso millet, and sorghum. The presence of both hemicelluloses in the
      spaces between cellulose fibrils and the unhydrolyzable and highly cross-linked
      lignocarbohydrate complex (LCC) determines a microporous (80% pores having
      diameters below 0.8 nm) structure of the cell wall that prevents the cellulase
      enzymes from coming into direct contact with the cellulose, as their sizes exceed
      the cell wall pore size. On the other hand, the removal of the hemicelluloses and
      of the LCC complex determines a reduction of the MiS and an increase of the
      available surface for enzymatic attack, i.e., pores >5 nm diameter. This was
      confirmed by the good negative (r = -0.87, P < 0.001, n = 11) and positive (r =
      0.78, P < 0.005, n = 11) correlations found for microporosity and mesoporosity
      (pores of diameters >5 nm), respectively, vs the glucose production, by cellulase
      enzyme attack in specific enzymatic hydrolysis tests performed on biomass
      samples.

PMID- 21174468
TI  - Rapid and sensitive Nitrosomonas europaea biosensor assay for quantification of
      bioavailable ammonium sensu strictu in soil.
AB  - Knowledge on bioavailable ammonium sensu strictu (i.e., immediately available for
      cellular uptake) in soil is required to understand nutrient uptake processes in
      microorganisms and thus of vital importance for plant production. We here present
      a novel ammonium biosensor approach based on the lithoautotrophic ammonia
      oxidizing bacterium Nitrosomonas europaea transformed with a luxAB sensor
      plasmid. Bioluminescence-based ammonium detection was achieved within 10 min with
      a quantification limit in liquid samples of ~20 MUM and a linear response range
      up to 400 MUM. Biosensor and conventional chemical quantification of ammonium in
      soil solutions agreed well across a range of sample and assay conditions. The
      biosensor was subsequently applied for a solid phase-contact assay allowing for
      direct interaction of biosensor cells with soil particle-associated (i.e.,
      exchangeable plus fixed) ammonium. The assay successfully quantified bioavailable
      ammonium even in unfertilized soil and demonstrated markedly higher ratios of
      bioavailable ammonium to water- or 2 M KCl-exchangeable ammonium in anoxic soil
      than in corresponding oxic soil. Particle-associated ammonium contributed by at
      least 74% and 93% of the total bioavailable pool in oxic and anoxic soil,
      respectively. The N. europaea biosensor should have broad relevance for
      environmental monitoring of bioavailable ammonium and processes depending on
      ammonium bioavailability.

PMID- 21174467
TI  - Kinetin increases chromium absorption, modulates its distribution, and changes
      the activity of catalase and ascorbate peroxidase in Mexican Palo Verde.
AB  - This report shows, for the first time, the effectiveness of the phytohormone
      kinetin (KN) in increasing Cr translocation from roots to stems in Mexican Palo
      Verde. Fifteen-day-old seedlings, germinated in soil spiked with Cr(III) and (VI)
      at 60 and 10 mg kg(-1), respectively, were watered every other day for 30 days
      with a KN solution at 250 MUM. Samples were analyzed for catalase (CAT) and
      ascorbate peroxidase (APOX) activities, Cr concentration, and Cr distribution in
      tissues. Results showed that KN reduced CAT but increased APOX in the roots of
      Cr(VI)-treated plants. In the leaves, KN reduced both CAT and APOX in Cr(III) but
      not in Cr(VI)-treated plants. However, KN increased total Cr concentration in
      roots, stems, and leaves by 45%, 103%, and 72%, respectively, compared to Cr(III)
      alone. For Cr(VI), KN increased Cr concentrations in roots, stems, and leaves,
      respectively, by 53%, 129%, and 168%, compared to Cr(VI) alone. The electron
      probe microanalyzer results showed that Cr was mainly located at the cortex
      section in the root, and Cr distribution was essentially homogeneous in stems.
      However, proven through X-ray images, Cr(VI)-treated roots and stems had more Cr
      accumulation than Cr(III) counterparts. KN increased the Cr translocation from
      roots to stems.

PMID- 21174469
TI  - Identification of key constituents and structure of the extracellular polymeric
      substances excreted by Bacillus megaterium TF10 for their flocculation capacity.
AB  - Extracellular polymeric substances (EPS), a complex high-molecular-weight mixture
      of polymers excreted by microorganisms and produced from cell lysis, may have a
      high bioflocculation activity. In this work, the EPS excreted from Bacillus
      megaterium TF10, which was isolated from a soil sample, were systematically
      characterized to give insights into the relationship between their specific
      constituents and structure with their flocculation capacity. The results of
      microscopic observation, zeta potential, and TF10 EPS structure analysis show
      that the bridging mechanism was mainly responsible for the flocculation of the
      TF10. The constituents with a large molecular weight (1037-2521 kDA) and
      functional groups had contributed to the flocculation. GC-MS and NMR analyses
      demonstrate that the polysaccharides had long chain composed of rhamnose as well
      as glucose and galactose with uronic acids, acetyl amino sugars, and proteins as
      the side chains. The proteins in TF10 had no flocculation ability because of
      their special secondary structure and molecular weight diffusion characters. The
      EPS from Bacillus megaterium TF10 were found to exhibit a high flocculation
      activity, and the polysaccharides in EPS, which have the structure of the long
      backbone with active side chains, were identified as the active constituents for
      the high flocculation activity.

PMID- 21174471
TI  - A highly diastereo- and enantioselective copper(I)-catalyzed Henry reaction using
      a bis(sulfonamide)-diamine ligand.
AB  - A series of bis(sulfonamide)-diamine (BSDA) ligands were synthesized from
      commercially available chiral alpha-amino alcohols and diamines. The chiral BSDA
      ligand 3a, coordinated with Cu(I), catalyzes the enantioselective Henry reaction
      with excellent enantioselectivity (up to 99%). Moreover, with the assistance of
      pyridine, a CuBr-3a system promotes the diastereoselective Henry reaction with
      various aldehyde substrates and gives the corresponding syn-selective adduct with
      up to a 99% yield and 32.3:1 syn/anti selectivity. The enantiomeric excess of the
      syn adduct was 97%.

PMID- 21174470
TI  - Angiotensin I-converting enzyme inhibitory activity of gelatin hydrolysates and
      identification of bioactive peptides.
AB  - In this project we report on the angiotensin I-converting enzyme (ACE)-inhibitory
      activity of a bovine gelatin hydrolysate (Bh2) that was submitted to further
      hydrolysis by different enzymes. The thermolysin hydrolysate (Bh2t) showed the
      highest in vitro ACE inhibitory activity, and interestingly a marked in vivo
      blood pressure-lowering effect was demonstrated in spontaneously hypertensive
      rats (SHR). In contrast, Bh2 showed no effect in SHR, confirming the need for the
      extra thermolysin hydrolysis. Hence, an angiotensin I-evoked contractile response
      in isolated rat aortic rings was inhibited by Bh2t, but not by Bh2, suggesting
      ACE inhibition as the underlying antihypertensive mechanism for Bh2t. Using mass
      spectrometry, seven small peptides, AG, AGP, VGP, PY, QY, DY and IY or LY or HO
      PY were identified in Bh2t. As these peptides showed ACE inhibitory activity and
      were more prominent in Bh2t than in Bh2, the current data provide evidence that
      these contribute to the antihypertensive effect of Bh2t.

PMID- 21174472
TI  - Forbidden singlet exciton transitions induced by localization in polymer light
      emitting diodes in a strong electric field.
AB  - Through combining the electron transition process and dipole moment evolution as
      well as electron-phonon coupling, molecular dynamics calculations show that the
      radiative decay of singlet excitons in a conjugated polymer, such as a polymer
      light-emitting diode (PLED), is largely determined by the evolution of the dipole
      moment. Without an electric field, the decay life of a singlet exciton is about 1
      ns. Once an electric field is applied and exceeds a critical value, with electron
      phonon coupling, the original lattice structure evolves into two new localized
      lattice distortions, consistent with the experimental results. Owing to the new
      lattice structure and self-trapping, the dipole moment rapidly decreases to zero
      within 5 fs, eliminating the radiative decay of the singlet exciton.

PMID- 21174474
TI  - Mechanism of trivalent gold reduction and reactivity of transient divalent and
      monovalent gold ions studied by gamma and pulse radiolysis.
AB  - The detailed kinetics of the multistep mechanism of the Au(III) ion reduction
      into gold clusters have been investigated by radiation chemistry methods in 2
      propanol. In particular, a discussion on the steady state radiolysis dose
      dependence of the yields concludes to a comproportionation reaction of nascent
      gold atoms Au(0) with excess Au(III) ions into Au(II) and Au(I). This reaction
      should be achieved through Au(III) consumption before the coalescence of atoms
      Au(0) into gold clusters may occur. Then gold clusters catalyze the reduction of
      Au(I) by 2-propanol. It was also found that a long-lived Au(II) dimer,
      (Au(II))(2), was transiently formed according to the quantitative analysis of
      time-resolved absorbance signals obtained by pulse radiolysis. Then the
      disproportionation of Au(II) is intramolecular in the dimer instead of
      intermolecular, as usually reported. The yields, reaction rate constants, time
      resolved spectra, and molar extinction coefficients are reported for the
      successive one-electron reduction steps, involving especially the transient
      species, such as Au(II), (Au(II))(2), and Au(I). The processes are discussed in
      comparison with other solvents and other metal ions.

PMID- 21174473
TI  - An enyne cycloisomerization approach to the triple reuptake inhibitor
      GSK1360707F.
AB  - The triple reuptake inhibitor GSK1360707F was synthesized via an efficient and
      scalable route that features an enyne cycloisomerization reaction catalyzed by
      either Pt(II) or Au(I). Key aspects of this work such as the choice of the
      nitrogen protecting group and initial enantioselectivity studies are discussed.

PMID- 21174475
TI  - Hydrolysis of imidazole-2-ylidenes.
AB  - The direct reaction of an imidazole-2-ylidene in a predominantly aqueous
      environment [about 0.1 M solution in a H(2)O (>60%)/THF solvent system] was
      investigated for the first time. The reaction yielded a stable solution of the
      corresponding imidazolium-hydroxide of pH 13, which is in agreement with results
      from an ab initio molecular dynamics simulation. In contrast, hydrolysis of the
      carbene in a mainly aprotic environment (>80% THF) gives a hydrogen-bridged
      carbene-water complex which could be detected by NMR and IR spectroscopies for
      the first time. This complex converts slowly to two isomeric ring opened products
      and is at higher water concentration in dynamic equilibrium with the imidazolium
      hydroxide. A computational mechanistic study of the carbene hydrolysis with a
      gradually increasing number of water molecules revealed that the imidazolium
      hydroxide structure can only be optimized with three or more water molecules as
      reactants, and with the increasing number of water molecules its stability is
      increasing with respect to the carbene-water complex. In agreement with the
      experimental results, these findings point out that solvent stabilization and
      basicity of the hydroxide ion plays a crucial role in the reaction. With
      increasing number of water molecules the barriers connecting the reaction
      intermediates are getting smaller, and the ring opened hydrolysis products can be
      derived from imidazolium-hydroxide type intermediates. Computational studies on
      the hydrolysis of a nonaromatic imidazolidine-2-ylidene analogue clearly
      indicated the analogous ring-opened product to be by 10-12 kcal/mol more stable
      than the appropriate ion pair and the carbene-water complex, in agreement with
      the known aromatic stabilization of imidazol-2-ylidenes. Accordingly, these
      molecules hydrolyze with exclusive formation of the ring-opened product.

PMID- 21174476
TI  - Simulation of the amide I absorption of stacked beta-sheets.
AB  - Aggregated beta-sheet structures are associated with amyloid and prion diseases.
      Techniques capable of revealing detailed structural and dynamical information on
      beta-sheet structure are thus of great biomedical and biophysical interest. In
      this work, the infrared (IR) amide I spectral characteristics of stacked beta
      sheets were modeled using the transition dipole coupling model. For a test set of
      beta-sheet stacks, the simulated amide I spectrum was analyzed with respect to
      the following parameters; intersheet distance, relative rotation of the sheets
      with respect to each other and the effect of number of sheets stacked. The amide
      I maximum shifts about 5 cm(-1) to higher wavenumbers when the intersheet
      distance between two identical beta-sheets decreases from 20 to 5 A. Rotation
      around the normal of one of the sheets relative to the other results in maximum
      intersheet coupling near 0 degrees  and 180 degrees . Upon of rotation from 0
      degrees  to 90 degrees  at an intersheet distance of 9 A, the amide I maximum
      shifts about 3 cm(-1). Tilting of one of the sheets by 30 degrees  from the
      normal results in a shift of the amide I maximum by less than 1 cm(-1). When
      stacking several beta-sheets along the normal, the amide I maximum shifts to
      higher wavenumbers with increasing stack size. The amide I maximum shifts about 6
      cm(-1) when stacking four sheets with an intersheet distance of 9 A. The study
      provides an aid in the interpretation of the IR amide I region for experiments
      involving beta-sheets and creates awareness of the many effects that determine
      the spectrum of beta-sheet structures.

PMID- 21174477
TI  - Structure-activity relationship of 4(5)-aryl-2-amino-1H-imidazoles, N1
      substituted 2-aminoimidazoles and imidazo[1,2-a]pyrimidinium salts as inhibitors
      of biofilm formation by Salmonella typhimurium and Pseudomonas aeruginosa.
AB  - A library of 112 4(5)-aryl-2-amino-1H-imidazoles, 4,5-diphenyl-2-amino-1H
      imidazoles, and N1-substituted 4(5)-phenyl-2-aminoimidazoles was synthesized and
      tested for the antagonistic effect against biofilm formation by Salmonella
      Typhimurium and Pseudomonas aeruginosa. The substitution pattern of the 4(5)
      phenyl group and the nature of the N1-substituent were found to have a major
      effect on the biofilm inhibitory activity. The most active compounds of this
      series were shown to inhibit the biofilm formation at low micromolar
      concentrations. Furthermore, the influence of 6 imidazo[1,2-a]pyrimidines and 18
      imidazo[1,2-a]pyrimidinium salts on the biofilm formation was tested. These
      compounds are the chemical precursors of the 2-aminoimidazoles in our synthesis
      pathway. A good correlation was found between the activity of the imidazo[1,2
      a]pyrimidinium salts and their corresponding 2-aminoimidazoles, supporting the
      hypothesis that the imidazo[1,2-a]pyrimidinium salts are possibly cleaved by
      cellular nucleophiles to form the active 2-aminoimidazoles. However, the
      imidazo[1,2-a]pyrimidines did not show any biofilm inhibitory activity,
      indicating that these molecules are not susceptible to in situ degradation to 2
      aminoimidazoles. Finally, we demonstrated the lack of biofilm inhibitory activity
      of an array of 37 2N-substituted 2-aminopyrimidines, which are the chemical
      precursors of the imidazo[1,2-a]pyrimidinium salts in our synthesis pathway.

PMID- 21174478
TI  - Many facets of the polyelectrolyte and oppositely charged colloidal particle
      complexation: counterion release and electrical conductivity behavior.
AB  - The lateral correlated adsorption of polyions onto oppositely charged vesicles,
      leading to the formation of stable equilibrium clusters of mesoscopic size, is
      associated to the release of a fraction of counterions, initially condensed on
      the polyion chains. This ulterior release of counterions provokes an increase of
      the number of free ions, besides the ones due to the partial ionization of both
      charged particles and polyions, that can be appropriately monitored by means of
      electrical conductivity measurements of the whole system. We have investigated
      this behavior in a suspension of cationic vesicles made up by dioleoyl trimethyl
      ammonium propane (DOTAP) liposomial vesicles interacting with an anionic
      polyelectrolyte composed by polyacrylate sodium salt. This system has been in the
      past extensively studied by us by means of different experimental techniques, and
      its behavior has been sufficiently characterized, as far as hydrodynamic and
      electrical properties are concerned. In this note, we report on the dc electrical
      conductivity behavior during the whole aggregation process, from the single
      polyion-coated liposomal particles, to polyion-induced liposome clusters, to
      finally polyion-fully covered liposomes, in polyion excess conditions. We have
      evaluated the excess of released counterions on the basis of the standard theory
      of the electrical properties of aqueous charged solutions and compared this
      quantity with the one predicted by the lateral correlation adsorption model. The
      agreement is quite good, offering strong experimental evidence of the role played
      by the release of counterions in the aggregation process. Finally, we have
      considered a similar liposomial system, where the lateral correlation adsorption
      was inhibited by structural reasons, having replaced the polyion by a simple
      electrolyte, whose dissociated ions will adsorb randomly at the particle surface,
      rather than in a correlated manner. In this case, no counterion release upon
      complexation occurs, and the electrical conductivity of the suspension approaches
      the one theoretically expected.

PMID- 21174479
TI  - The Chinese healthcare system: structure, problems and challenges.
AB  - We describe the structure and present situation of the Chinese healthcare system
      and discuss its primary problems and challenges. We discuss problems with
      inefficient burden sharing, adverse provider incentives and huge inequities, and
      seek explanations in the structural features of the Chinese healthcare system.
      The current situation will be further challenged in the future by an aging
      population, an increasing need for privatization and growing expectations about
      quality of healthcare.

PMID- 21174480
TI  - Costs to hospitals of acquiring and processing blood in the US: a survey of
      hospital-based blood banks and transfusion services.
AB  - BACKGROUND: little is known about the economics of acquiring and processing the
      more than 14 million units of red blood cells used annually in the US. OBJECTIVE:
      to determine the average price paid by hospitals to suppliers for a unit of red
      blood cells and to identify cost variations by region and facility type and size.
      A secondary objective was to examine costs for additional blood components as
      well as costs for blood-related processes performed by hospitals. Qualitative
      input was sought to identify potential cost drivers. METHODS: a cross-sectional
      survey was performed of a randomized sample of hospital-based blood bank and
      transfusion service directors. The survey instrument assessed costs of specific
      blood components and services as incurred by hospitals. Analysis of variance was
      performed to test for significant variation in costs for red blood cells by
      geographic region and division, facility type and bed capacity. RESULTS: a total
      of 213 surveys were completed. The mean (SD) acquisition cost for one unit of red
      blood cells purchased from a supplier (n = 204) was $US210.74 +/- 37.9 and the
      mean charge to the patient (n = 167) was $US343.63 +/- 135. There was significant
      statistical variation in acquisition cost by US census region (p < 0.0001) and
      division (p < 0.0001). Teaching hospitals were more likely to receive volume
      discounts than other facility types. The mean prices paid per unit for fresh
      frozen plasma (n = 167) and apheresis platelets (n = 153) were $US60.70 +/- 20
      and $US533.90 +/- 69, respectively. The median cost for mandated screening
      performed onsite (n = 56) was $US50.00 +/- 120 and the median storage and
      retrieval cost (n = 46) was $US68.00 +/- 81 per unit. A total of 28% of
      respondents reported that costs for acquisition, screening and transfusion had
      'increased dramatically' over the past 5 years and 23% reported that blood
      shortages were a significant problem. CONCLUSIONS: the cost of blood continues to
      increase and price varies by geography. However, the rate of increase in
      acquisition costs for red blood cells appears to be slowing. This information
      should be used by organizations and policy makers to improve financing and
      utilization management for blood components and services.

PMID- 21174481
TI  - Determinants of out-of-pocket health expenditure in China: analysis using China
      Health and Nutrition Survey data.
AB  - BACKGROUND: within total health expenditure, the share of out-of-pocket health
      expenditure by individuals has increased in the past 25 years in China, from 20%
      in 1980 to 49% in 2006, with a peak of 59% in 2000. Medical issues have become a
      larger concern than any other issue for households. OBJECTIVE: to estimate the
      determinants of individual out-of-pocket health expenditure in China. METHODS: we
      used a subsample of 9860 adults aged >= 18 years from the 2004 China Health and
      Nutrition Survey. To control for potential sample selection bias, the Heckman
      selection model was used to analyse individuals' health expenditure decisions,
      which is based on a sample that excludes individuals who do not report paying for
      healthcare. RESULTS: of the sampled population, 24.6% reported recent illness,
      80.6% of whom sought care; 82.3% of those who sought care reported the amount of
      health spending. The average out-of-pocket health expenditure was Chinese Yuan
      (Y) 502 (Y100 = $US12.2 in 2004). Illness perceived as 'quite serious' and self
      reported poor health status had the highest coefficients (2.012 [p < 0.01] and
      3.351 [p < 0.01], respectively). People spent more on healthcare with increasing
      age, especially over the age of 65 years, with a coefficient of 1.171 (p < 0.01).
      Those who had chronic disease, earned higher incomes, resided in urban areas,
      lived in the middle or eastern region, or lived in a household with a head having
      a middle school or higher education paid more for healthcare. In the model
      examining disaggregated effects of insurance programmes, the coefficients were
      positive, except for commercial insurance, and the coefficient for labour
      insurance was significant. CONCLUSION: perceived severity of illness and self
      reported health status are the most important factors when determining out-of
      pocket health expenditure. The effect of aging is substantial. China should
      develop appropriate medical relief policies for the elderly to help them gain
      access to necessary healthcare services. Certain types of insurance programmes
      tend to increase out-of-pocket health expenditures, which highlights the need to
      continuously monitor and rigorously evaluate the impact of ongoing health
      insurance reform in China.

PMID- 21174482
TI  - The impact of CT colonography for colorectal cancer screening on the UK NHS:
      costs, healthcare resources and health outcomes.
AB  - BACKGROUND: Biennial faecal occult blood testing (FOBT) for individuals aged 60
      69 years is the primary screening tool for colorectal cancer (CRC) in the UK NHS,
      despite a large number of patients undergoing an unnecessary optical colonoscopy
      (OC) and evidence from modelling studies to suggest that more cost-effective
      technologies exist. CT colonography (CTC) is an emerging CRC screening technology
      with the potential to prevent CRC by detecting pre-cancerous polyps and to detect
      cancer at an earlier stage. OBJECTIVE: to assess the impact of introducing CTC
      into the UK NHS screening programme for CRC on key health outcomes as well as the
      NHS budget and healthcare resource capacity. METHODS: a discrete Markov model was
      used to reflect the natural history of CRC and the impact of three screening
      scenarios (biennial FOBT with and without CTC triage of patients referred to OC,
      and CTC every 5 years) on a range of health outcomes, including the incidence and
      prevalence of CRC, in a hypothetical cohort of individuals. The yearly costs,
      health outcomes and healthcare resource capacity requirements were estimated over
      a 10-year period (2009-18). RESULTS: using CTC to follow up FOBT-positive
      patients (scenario 2) was less costly than directing all FOBT-positive patients
      to OC (scenario 1); saving L776 283 over 10 years for 100 000 individuals invited
      for screening (year 2007 values), primarily by avoiding approximately 1700 OCs,
      but was estimated to require 2200 additional CT scans. Implementing a programme
      of 5-yearly CTC as a primary screen is expected to be more expensive than FOBT
      screening over the short term (driven by high screening and diagnosis costs),
      despite substantial savings in treatment costs for CRC over the 10-year time
      horizon of the model and improved health outcomes. CONCLUSIONS: adding CTC into
      the existing NHS Bowel Cancer Screening Programme as part of a preventive
      screening strategy could be less costly to the NHS over the longer term when used
      to triage FOBT-positive patients to appropriate follow-up. Increased demand for
      radiology services may be compensated for by reduced demand in endoscopy units.

PMID- 21174484
TI  - Prevention and management of prosthetic joint infection in older adults.
AB  - Total joint arthroplasty (TJA) is commonly performed on older adults. Prosthetic
      joint infection (PJI) is a serious complication of TJA that can significantly
      impact quality of life and physical function. In this review, we discuss the
      epidemiology and risk factors for PJIs among older adults. We also offer an
      overview of current diagnostic, treatment and management strategies for PJI.
      Given the serious nature of PJI, prevention efforts remain essential. Several
      approaches to infection prevention exist, including antimicrobial prophylaxis and
      decolonization. Although there are standardized recommendations for antimicrobial
      prophylaxis, the specific regimens must be individualized based on the patient's
      drug allergies, potential for drug interactions, renal function and bodyweight.
      The best approach to pre-operative screening and decolonization programmes
      remains unclear. Each of these issues is reviewed in detail with a focus on
      adverse effects and current debates regarding best practice. Given the increased
      numbers of TJAs performed, additional research on prevention and management is
      critical.

PMID- 21174483
TI  - Potential predictors of hippocampal atrophy in Alzheimer's disease.
AB  - The hippocampus is a vulnerable and plastic brain structure that is damaged by a
      variety of stimuli, e.g. hypoxia, hypoperfusion, hypoglycaemia, stress and
      seizures. Alzheimer's disease is a common and important disorder in which
      hippocampal atrophy is reported. Indeed, the available evidence suggests that
      hippocampal atrophy is the starting point of the pathogenesis of Alzheimer's
      disease and a significant number of patients with hippocampal atrophy will
      develop Alzheimer's disease. Studies indicate that hippocampal atrophy has
      functional consequences, e.g. cognitive impairment. Deposition of tau protein,
      formation of neurofibrillary tangles and accumulation of beta-amyloid (Abeta)
      contributes to hippocampal atrophy together with damage caused by several other
      factors. Some of the factors associated with the development of hippocampal
      atrophy in Alzheimer's disease have been identified, e.g. hypertension, diabetes
      mellitus, hyperlipidaemia, seizures, affective disturbances and stress, and more
      is being learnt about other factors. Hypertension can potentially damage the
      hippocampus through ischaemia caused by atherosclerosis and cerebral amyloid
      angiopathy. Diabetes can produce hippocampal lesions via both vascular and non
      vascular pathologies and can reduce the threshold for hippocampal damage.
      Carriers of the apolipoprotein E (ApoE)-epsilon4 genotype have been shown to have
      greater mesial temporal atrophy and poorer memory functions than non-carriers. In
      addition to giving rise to abnormal lipid metabolism, the ApoE-epsilon4 allele
      can affect the course of Alzheimer's disease via both Abeta-dependent and 
      independent pathways. Repetitive seizures can increase Abeta-peptide production
      and cause neurotransmission dysfunction and cytoskeletal abnormalities or a
      combination of these. Affective disturbances and stress are proposed to increase
      corticosteroid-induced hippocampal damage in many different ways. In the absence
      of any specific markers for predicting Alzheimer's disease progression, it seems
      appropriate to learn more about the various predictors of hippocampal atrophy
      that determine the progression of Alzheimer's disease from mild cognitive
      impairment (MCI), and then attempt to address these. It would be interesting to
      know to what extent these predictors play a role in the development of MCI or
      hasten the conversion of MCI to full-blown Alzheimer's disease. Finally, it would
      be useful to know the extent to which these predictors can worsen or aggravate
      existing Alzheimer's disease. Of the clinically used drugs in Alzheimer's
      disease, anticholinesterases have been shown to slow down the rate of progression
      of hippocampal atrophy. One study observed that the neuroprotective effect of
      these agents is possibly due to an anti-Abeta effect produced by cholinergic
      stimulation. Similarly, antihypertensive and antihyperglycaemic drugs
      (pioglitazone and insulin) have been shown to reduce the risk of Alzheimer's
      disease or disease progression. Currently, there are no disease-modifying
      therapies available for Alzheimer's disease. It has been suggested that for
      treatment to be most effective, the regimen must be started before significant
      downstream damage has occurred (i.e. before the clinical diagnosis of Alzheimer's
      disease, at the stage of MCI or earlier). Since the hippocampus is a plastic
      structure and atrophy of this structure is closely related to the pathophysiology
      of Alzheimer's disease, if we could control blood pressure, regulate blood sugar,
      treat behavioural and psychological symptoms, achieve satisfactory lipid lowering
      and maintain a seizure-free state in patients with Alzheimer's disease, this may
      not only improve disease control but could also potentially affect the rate of
      disease progression.

PMID- 21174485
TI  - Safety and efficacy of topical diclofenac sodium gel for knee osteoarthritis in
      elderly and younger patients: pooled data from three randomized, double-blind,
      parallel-group, placebo-controlled, multicentre trials.
AB  - BACKGROUND: NSAIDs used for the treatment of osteoarthritis (OA) have dose
      related risks for gastrointestinal, cardiovascular and renal adverse events
      (AEs), particularly in elderly patients. Topical NSAIDs reduce systemic NSAID
      exposure and may mitigate these risks. OBJECTIVE: To evaluate the safety and
      efficacy of topical diclofenac sodium 1% gel (DSG) versus vehicle in patients
      aged 25-64 or >=65 years who have been diagnosed with knee OA. STUDY DESIGN:
      Pooled data from three 12-week, randomized, double-blind, parallel-group,
      multicentre trials. SETTING: US primary care, internal medicine, orthopaedic and
      rheumatology practices. PATIENTS: Aged >=25 years with mild to moderate (Kellgren
      Lawrence grade 1-3) knee OA. INTERVENTION: After a 1-week analgesic washout,
      patients applied 4 g of DSG or vehicle four times daily to one knee. Rescue
      paracetamol (acetaminophen) up to 4 g/day was allowed. MAIN OUTCOME MEASURE: Key
      efficacy outcomes common to the three trials were Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC) pain (0-20) and physical function (0
      68) subscales, global rating of disease (GRD; 100-mm visual analogue scale [VAS])
      and pain on movement (POM; 100-mm VAS). ANOVA was used to compare efficacy
      outcome differences (DSG vs vehicle) by age (25-64 or >=65 years). A flare design
      was used that defined a subset of patients who experienced increased pain during
      the washout period (modified efficacy subpopulation [MES]). RESULTS: The MES
      included both patients aged 25-64 (n = 602) and >=65 (n = 374) years. Patients in
      each age group applied >90% of scheduled doses. Among patients aged 25-64 years,
      the improvement from baseline to week 12 (least squares mean [standard error])
      was greater for DSG versus vehicle for WOMAC pain (-5.8 [0.3] vs -4.7 [0.3], p =
      0.007), WOMAC physical function (-17.9 [0.9] vs -14.2 [0.9], p = 0.002), GRD (
      29.5 [1.6] vs -23.8 [1.6], p = 0.01) and POM (-37.3 [1.8] vs -29.0 [1.8], p <
      0.001). Among patients aged >=65 years, the improvements from baseline for most
      efficacy outcome scores were significantly greater with DSG versus vehicle: WOMAC
      pain (-5.3 [0.3] vs -4.1 [0.4], p = 0.02), WOMAC physical function (-15.5 [1.1]
      vs -11.0 [1.1], p = 0.004) and POM (-33.7 [2.2] vs -26.4 [2.2], p = 0.02). The
      efficacy of DSG did not differ significantly between patients aged 25-64 years
      and >=65 years: WOMAC pain (p = 0.85), WOMAC physical function (p = 0.70), GRD (p
      = 0.86) and POM (p = 0.81). The incidence of any AE was greater with DSG than
      with vehicle among patients aged 25-64 years (56.6% vs 50.8%) and >=65 years
      (55.8% vs 43.9%). Treatment-related application site dermatitis was more common
      with DSG compared with vehicle in both younger (4.0% vs 0.7%, respectively) and
      older (5.8% vs 0.4%, respectively) patients and was the main reason for the
      difference in treatment-related AEs between the DSG and vehicle groups.
      Gastrointestinal AEs were infrequent among patients treated with DSG and similar
      to incidence rates with vehicle in both age groups. CONCLUSIONS: DSG was
      effective and generally well tolerated in adults regardless of age. These data
      support the topical application of DSG for relief of OA knee pain in elderly and
      younger patients. Clinicaltrials.gov registration numbers NCT00171626,
      NCT00171678, NCT00426621.

PMID- 21174486
TI  - Elimination of intravenous oxycodone in the elderly: a pharmacokinetic study in
      postoperative orthopaedic patients of different age groups.
AB  - BACKGROUND AND OBJECTIVE: Oxycodone is a widely used opioid analgesic, the global
      use of which has increased several-fold during the last decade. This study was
      designed to determine the effect of age on the pharmacokinetics of intravenous
      oxycodone, with special reference to renal function in elderly patients. METHODS:
      We compared the pharmacokinetics of 5 mg of intravenous oxycodone in four groups
      of 10-11 patients, aged 20-40, 60-70, 70-90 years, undergoing orthopaedic
      surgery. Plasma concentrations of oxycodone and its noroxycodone, oxymorphone and
      noroxymorphone metabolites were measured for 24 hours with a liquid
      chromatography-tandem mass spectrometric method. The cytochrome P450 (CYP) 2D6
      genotype of the patients was determined. Glomerular filtration rate (GFR) was
      estimated on the basis of the age, sex and serum creatinine concentration of the
      patient. RESULTS: The pharmacokinetics of oxycodone showed age dependency. In the
      oldest group, the mean area under the plasma concentration-time curve from time
      zero to infinity (AUC(infinity)) of oxycodone was 80% greater (p < 0.001) and the
      apparent total body clearance of the drug from plasma (CL) was 34% lower (p <
      0.05) than in the youngest group. The mean AUC(infinity) of oxycodone was also 30
      41% greater in the oldest group than in the age groups of 60-70 and 70-80 years
      (p < 0.05). Oxycodone plasma concentrations from 8 hours post-dose were >2-fold
      higher (p < 0.01) in patients aged >80 years than in patients aged 20-40 years.
      Noroxycodone AUC(infinity) was increased in the oldest group compared with
      patients aged 20-40 and 60-70 years (p < 0.05). There were no significant sex
      related differences in any of the pharmacokinetic parameters. Because 37 of the
      41 patients were extensive metabolizers through CYP2D6, the effect of the CYP2D6
      genotype on oxycodone pharmacokinetics could not be properly assessed. There was
      a linear correlation between GFR and CL (p < 0.01, coefficient of determination
      [r(2)] = 0.26), volume of distribution at steady state (p < 0.05, r(2) = 0.19)
      and AUC(infinity) (p < 0.01, r(2) = 0.29) of oxycodone. CONCLUSIONS: Age is an
      important factor affecting the pharmacokinetics of oxycodone. Following
      intravenous administration of oxycodone, patients aged >70 years are expected to
      have, on average, 40-80% higher exposure to oxycodone than young adult patients.
      Because oxycodone pharmacokinetics are greatly dependent on the age of the
      patient, it is important to titrate the analgesic dose individually, particularly
      in the elderly.

PMID- 21174487
TI  - Physicians' decisions to prescribe antidepressant therapy in older patients with
      depression in a US managed care plan.
AB  - BACKGROUND: Published studies indicate that depression in older adults is
      severely under-recognized and under-treated. OBJECTIVE: To characterize primary
      care physicians' decisions to prescribe antidepressants to older patients with
      depression. METHODS: Electronic medical record (EMR) notes from office visits of
      older patients (aged >=65 years), treated in a central Massachusetts multi
      specialty medical group practice, were screened every 2 weeks between August 2007
      and July 2008 for mention of depression. Electronic surveys containing questions
      about depression severity and onset, and antidepressant treatment, were sent to
      physicians whose EMR notes indicated that they had treated an older patient with
      depression, until approximately 400 responses had been received. Physicians were
      asked about whether they prescribed antidepressants or made changes to
      antidepressant treatment and were asked about the extent to which they agreed
      with a set of pre-specified reasons for treatment recommendations. Physicians
      were also allowed to document any other reasons that influenced their decision.
      Patient characteristics and treatment were identified from administrative claims.
      Univariate analyses were used to describe patient characteristics and physician
      survey responses. RESULTS: Physicians responded to the survey and confirmed a
      depression diagnosis for 396 patients, for whom the average age was 77.1 years
      and 76.5% were female. Most patients had physician-reported depression onset
      after age 60 years (72.2%) and moderately severe depression (58.8%). Physicians
      reported that 62.9% of patients were already being treated with antidepressants
      prior to their visit, 28.5% were recommended antidepressant initiation and 8.6%
      were not prescribed antidepressants. Selective serotonin reuptake inhibitors were
      most frequently prescribed. Maintaining prior therapy was recommended for 81.1%
      of treated patients and treatment modification for 18.9%. Almost all physicians
      (>92%) agreed that experience in use of prescription drugs, safety/tolerability
      and patient improvement influenced their decision to maintain prior therapy or
      recommend new therapy. 85.8% of physicians agreed that availability of efficacy
      data in the elderly influenced their decision to prescribe new therapy. 38.9% of
      patients who were recommended new therapy initiation did not fill an
      antidepressant prescription. CONCLUSIONS: Despite previous reports of under
      treatment of depression in the elderly, this study suggests that physicians are
      comfortable prescribing antidepressants to the elderly, and the majority of older
      patients with depression were prescribed antidepressants. Rather than a
      physician's prescribing decision, it may be patient factors, such as refusal to
      accept diagnosis/treatment and noncompliance, that may lead to under-treatment-
      approximately 40% of patients who were recommended new antidepressant therapy did
      not fill an antidepressant prescription.

PMID- 21174488
TI  - Denosumab: a review of its use in the treatment of postmenopausal osteoporosis.
AB  - Denosumab (Prolia(r)) is a human recombinant monoclonal antibody that is approved
      for the treatment of postmenopausal osteoporosis in women at high or increased
      risk of fracture in the US, the EU and several other countries. Denosumab has a
      novel mechanism of action; it binds to receptor activator of nuclear factor
      kappaB ligand and inhibits bone resorption by inhibiting osteoclast formation,
      function and survival. In postmenopausal women with osteoporosis, denosumab
      reduced the risk of vertebral, nonvertebral and hip fractures compared with
      placebo over 3 years in the large, phase III FREEDOM study. In postmenopausal
      women with low bone mineral density (BMD) or osteoporosis, treatment with
      denosumab increased BMD and decreased markers of bone turnover more than
      alendronate in those who were essentially treatment-naive in the 1-year DECIDE
      study and also in the 1-year STAND study, in which women were switched from
      alendronate to denosumab or continued alendronate treatment. Denosumab was
      generally well tolerated in clinical trials, although long-term effects of very
      low bone turnover remain to be established. Denosumab is administered once every
      6 months via subcutaneous injection, which may be a preferred method of
      administration and may improve adherence to treatment compared with other
      osteoporosis treatments. Denosumab is a valuable new option for the treatment of
      postmenopausal osteoporosis in women at increased or high risk of fractures, and
      may be useful as a first-line treatment in women at increased risk of fractures
      who are unable to take other osteoporosis treatments.

PMID- 21174489
TI  - Bone marrow mesenchymal stromal cells with support of bispecific antibody and
      ultrasound-mediated microbubbles prevent myocardial fibrosis via the signal
      transducer and activators of transcription signaling pathway.
AB  - BACKGROUND AIMS: This study was initiated to investigate the efficacy of
      myocardial fibrosis intervention via signal transducer and activators of
      transcription (STAT) signaling using bone marrow (BM) mesenchymal stromal cells
      (MSC) with the aid of bispecific antibody (BiAb) and ultrasound-mediated
      microbubbles (MB). METHODS: BiAb (anti-CD29 * anti-myosin light chain antibody;
      AMLCA) was prepared and combined with isolated MSC from male mice and transfused
      into female mice with isoproterenol-induced myocardial fibrosis via the tail
      vein, followed by MB (MSC + BiAb + MB). This study included seven groups: MSC +
      BiAb + MB; MSC; BiAb; MB; MSC + BiAb; untreated; and control. Five weeks after
      treatment, expression levels of the sex-determining region of Y-chromosome (SRY),
      matrix metalloproteinases (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1
      and vascular endothelial growth factor (VEGF) in myocardium were detected by
      fluorescent quantitative real-time polymerase chain reaction (qRT-PCR). Collagen
      distribution was observed using Sirius Red staining. The protein expression of
      signal transducer and activators of transcription (STAT)1 and STAT3 was detected
      by Western blot. RESULTS: The highest homing number of MSC was in the MSC + BiAb
      + MB group, second highest in the MSC + BiAb group, and lowest in MSC alone.
      Compared with the untreated group, MSC + BiAb + MB, MSC + BiAb and MSC groups had
      decreased levels of MMP-9, TIMP-1, STAT1 and collagen deposition, and increased
      levels of STAT3. Upregulated STAT3 and downregulated TIMP-1 were significantly
      different in MSC + BiAb + MB compared with MSC alone or MSC + BiAb. CONCLUSIONS:
      The homing rate and repairing efficacy of MSC improved with treatment utilizing a
      combination of BiAb and MB. MSC can improve MMP-TIMP expression in injured
      myocardium and interfere with myocardial fibrosis after homing, a mechanism that
      may be related to the STAT-mediated signaling pathway.

PMID- 21174490
TI  - Transiently redirected T cells for adoptive transfer.
AB  - BACKGROUND AIMS: T cells can be redirected to reject cancer by retroviral
      transduction with a chimeric antigen receptor (CAR) or by administration of a
      bispecific T cell engager (BiTE). We demonstrate that transfection of T cells
      with messenger (m) RNA coding for CAR is an alternative strategy. METHODS: We
      describe the pre-clinical evaluation of a method based on transient modification
      of expanded T cells with a CD19 CAR directed against B-cell malignancies. CAR
      mRNA was generated under cell-free conditions in a scalable process using
      recombinant RNA polymerase. Efficient and non-toxic square-wave electroporation
      was used to load the mRNA into the cytoplasm of T cells with no risk of
      insertional mutagenesis. RESULTS: After transfection >80% of T cells were viable,
      with 94% CAR expression. Transfected T cells were cytolytic to CD19(+) targets
      and produced interferon (IFN)-gamma in response. Killing of CD19(+) target cells
      was demonstrated even at day 8 with undetectable CAR expression. Increasing the
      concentration of mRNA resulted in higher surface CAR expression, better killing
      and more IFN-gamma release but at the expense of increased activation-induced
      cell death. Finally, we demonstrated that a second transgene could be introduced
      by co-electroporation of CXCR4 or CCR7 with CAR to also modify chemotactic
      responses. CONCLUSIONS: We advocate the transient redirection approach as well
      suited to meet safety aspects for early phase studies, prior to trials using
      stably transduced cells once CAR has been proven safe. The simplicity of this
      methodology also facilitates rapid screening of candidate targets and novel
      receptors in pre-clinical studies.

PMID- 21174491
TI  - Clinical outcome of assertive community treatment (ACT) in a rural area in
      Denmark: a case-control study with a 2-year follow-up.
AB  - AIM: The aim of the present study was to evaluate the effect of assertive
      community treatment (ACT) in the Tonder Region, South Jutland, where the first
      Danish ACT team was established to treat patients with severe and persistent
      mental illness (SMI). METHODS: The study compares outcome over a 2-year period
      between recipients of ACT and standard community mental healthcare. RESULTS: The
      study included 86 cases and 88 controls. At the time of recruitment, the cases
      and the controls did not differ significantly in demographic details and
      eligibility criteria. At the 2-year follow-up, the ACT patients showed a
      significant reduction in admissions, bed days and day hospital days, and a
      significant increase in the number of consultations compared with the controls.
      Adherence to outpatient services was higher in the ACT group. No significant
      improvements in psychopathology were found after 2 years, but a significant
      improvement in met needs and fewer unmet needs, indicating better functioning,
      occurred. Clients' satisfaction with care (Client Satisfaction Questionnaire,
      CSQ) was significantly higher among ACT patients than among controls. CONCLUSION:
      The treatment of these patients in this ACT service has yielded promising
      results, suggesting that ACT treatment may be a useful intervention for SMI
      patients. However, large, rigorous, randomized control trials with ACT are needed
      in Europe as the existing evidence mainly comes from American studies.

PMID- 21174492
TI  - Psychometric properties and norm data of the Swedish version of the NEO-PI-R.
AB  - BACKGROUND: Internationally, the NEO Personality Inventory-Revised (NEO-PI-R) is
      a well established questionnaire for assessment of personality in accordance with
      the Five Factor Model. The instrument has been translated into many languages
      including Swedish. AIM: The aim of this study was to make a psychometric
      evaluation of the Swedish version of NEO-PI-R based on a sample from the general
      population. METHODS: Postal questionnaires were sent to a random sample of 1250
      persons (n = 766 responders). RESULTS AND CONCLUSIONS: The test showed
      satisfactory internal consistency in the broad factors as well as the facets. A
      factor analysis indicated that the factors were similar but not identical to
      those obtained in American studies. In sum, The Swedish version of the NEO-PI-R
      shows satisfactory psychometric properties and the instrument will continue to be
      a valuable tool in psychological research and in clinical practice.

PMID- 21174493
TI  - Successful management of gastrointestinal pythiosis in a dog using itraconazole,
      terbinafine, and mefenoxam.
AB  - Medical therapy for pythiosis is hampered by a lack of efficacious drugs. The
      present report describes a case of canine gastrointestinal pythiosis in which
      lesions were resolved through the administration of itraconazole, terbinafine,
      and the agricultural fungicide mefenoxam. No substantial adverse effects occurred
      in association with administration of the latter compound. Additional studies are
      needed to evaluate the pharmacokinetics of mefenoxam and to further assess its
      tolerability and potential efficacy for the treatment of pythiosis in dogs.

PMID- 21174494
TI  - Pulmonary fungal infection caused by Neoscytalidium dimidiatum in a Risso's
      dolphin (Grampus griseus).
AB  - Neoscytalidium dimidiatum was isolated from two 12-18 cm abscesses in the lung
      and the mediastinal lymph nodes of a stranded Risso's dolphin (Grampus griseus).
      Histopathologic examination of samples of these organs revealed the presence of
      hyphae and sclerotic body-like fungal elements. Photobacterium damselae subsp.
      damselae was recovered from the dolphin's organs which also were found to contain
      numerous Monorygma grimaldii cysts. No histopathological signs of morbillivirus
      infection were seen. To the best of our knowledge, this is the first report of N.
      dimidiatum infection in a sea mammal.

PMID- 21174495
TI  - How spacing of data collection may impact estimates of substance use
      trajectories.
AB  - The goal of this study is to provide an empirical example using longitudinal
      cigarette smoking data that compares results of growth mixture trajectory models
      on the basis of contiguous and snapshot measurements. Data were drawn from an
      intensive longitudinal study of college freshman (N = 905) with a previous
      history of smoking. Participants provided weekly smoking reports for 35
      consecutive weeks. We found that using contiguous weekly data (35 waves) or 6
      wave or 4-wave snapshot data provided similar trajectory curves and proportions.
      However, there were notable differences in individual trajectory assignments on
      the basis of contiguous and snapshot measurements.

PMID- 21174496
TI  - Gender differences in substance use, consequences, motivation to change, and
      treatment seeking in people with serious mental illness.
AB  - Gender differences in patterns and consequences of substance use, treatment
      seeking, and motivation to change were examined in two samples of people with
      serious mental illness (SMI) and comorbid substance use disorders (SUDs): a
      community sample not currently seeking substance abuse treatment (N = 175) and a
      treatment-seeking sample (N = 137). In both groups, women and men demonstrated
      more similarities in the pattern and severity of their substance use than
      differences. However, treatment-seeking women showed greater readiness to change
      their substance use. Mental health problems and traumatic experiences may prompt
      people with SMI and SUD to enter substance abuse treatment, regardless of gender.

PMID- 21174497
TI  - Impact of zinc fingers and homeoboxes 3 on the regulation of mesenchymal stem
      cell osteogenic differentiation.
AB  - We propose zinc fingers and homeoboxes 3 (ZHX3) as new osteogenic markers for
      mesenchymal stem cells (MSC). ZHX3 mRNA expression was upregulated within 1-6 h
      after incubation of MSCs in the osteogenic induction medium, and reached maximum
      levels after 24 h of incubation. Two to 4 days later, ZHX3 mRNA levels had
      decreased sharply. Maximal mRNA levels were 3- to 5-fold higher than those in the
      undifferentiated state. In contrast, Runt-related transcription factor2 (RUNX2)
      mRNA expression was downregulated at 2-4 h after incubation, and levels were only
      enhanced 1.4-fold after 12 and 24 h of incubation. Further, Osterix mRNA levels
      increased only 1.6-fold after 4 and 24 h of incubation. Thus, ZHX3 expression may
      be a better marker of MSC osteogenic differentiation than RUNX2 or Osterix
      expression at the initial stage of differentiation. Knockdown of ZHX3 using 2
      distinct small interfering RNA (siRNA) oligonucleotides had little effect on cell
      morphology or on MSC proliferation, regardless of the differentiation state of
      the cells. However, ZHX3 siRNAs suppressed Osterix, but not RUNX2 mRNA
      expression, within 1 h of osteogenic differentiation, and this suppression was
      sustained for at least 24 h. The 2 ZHX3 siRNAs also suppressed alkaline
      phosphatase induction and matrix mineralization (assessed using alizarin red
      staining), and, further, suppressed the calcium content of the cultures at a
      later stage of differentiation (days 6-21). The effects of ZHX3 siRNAs on the
      osteogenic differentiation were comparable to those of RUNX2 and Osterix siRNAs.
      These findings suggest that ZHX3 is involved in the switch from the
      undifferentiated state of MSC to an osteogenic program, and that ZHX3 may be
      useful as an early osteogenic differentiation marker.

PMID- 21174498
TI  - CHAT: development and validation of a computer-delivered, self-report, substance
      use assessment for adolescents.
AB  - The current study was conducted to construct and validate a computer-delivered,
      multimedia, substance use self-assessment for adolescents. Reliability and
      validity of six problem dimensions were evaluated in two studies, conducted from
      2003 to 2008. Study 1 included 192 adolescents from five treatment settings
      throughout the United States (N = 142) and two high schools from Greater Boston,
      Massachusetts (N = 50). Study 2 included 356 adolescents (treatment: N = 260;
      school: N = 94). The final version of Comprehensive Health Assessment for Teens
      (CHAT) demonstrated relatively strong psychometric properties. The limitations
      and implications of this study are noted. This study was supported by an SBIR
      grant.

PMID- 21174499
TI  - The relationship between source of diversion and prescription drug misuse, abuse,
      and dependence.
AB  - The current research examines the relationship between how people obtain
      prescription drugs (source of diversion) and how people misuse prescription drugs
      (i.e., frequency, abuse, and dependence). We analyzed data from the 2008 National
      Survey on Drug Use and Health public use file, a sample of 68,736 persons aged 12
      and older that is generalizable to the noninstitutionalized population of the
      United States. A number of regression models were estimated, and findings
      indicate that source of diversion was significantly correlated to frequency of
      prescription drug misuse, abuse, and dependence. Given these findings, we believe
      any attempt to classify prescription drug misusers based on certain
      characteristics should include source of diversion.

PMID- 21174500
TI  - Jello shot consumption among older adolescents: a pilot study of a newly
      identified public health problem.
AB  - We investigated the extent of jello shot consumption among underage youths. We
      conducted a pilot study among a nonrandom national sample of 108 drinkers, aged
      16-20 years, recruited from the Knowledge Networks Internet panel in 2010 by
      using consecutive sampling. The prevalence of past 30-day jello shot consumption
      among the 108 drinkers, aged 16-20 years, in our sample was 21.4%, and among
      those who consumed jello shots, the percentage of alcohol consumption
      attributable to jello shots averaged 14.5%. We concluded that jello shot use is
      prevalent among youths, representing a substantial proportion of their alcohol
      intake. Surveillance of youth alcohol use should include jello shot consumption.

PMID- 21174502
TI  - Preventing suicide in young people: systematic review.
AB  - OBJECTIVE: Risk of suicide attempt, suicidal ideation and deliberate self-harm is
      high among young people, yet limited evidence exists regarding effective
      interventions, particularly from randomized controlled trials. The aim of this
      study was to conduct a systematic review and meta-analysis of all randomized
      controlled trials testing interventions for adolescents and young adults who have
      presented to a clinical setting with any of these behaviours. METHODS: The
      Cochrane Central Register of Controlled Trials, Medline, EMBASE and PsycINFO were
      searched for articles published from 1980 to June 2010. The following keywords
      formed the basis of the search strategy: 'self-injurious behaviour', 'attempted
      suicide', 'suicide', 'suicidal behaviour', 'self-inflicted wounds', 'self
      mutilation', 'self-harm'. We also hand searched conference abstracts from two
      major suicide prevention conferences and the reference lists of all retrieved
      articles and previous reviews. RESULTS: There were 15 trials included in the
      review, with six ongoing trials also identified. In general, the reporting of the
      conduct of trials was poor, making it difficult to assess the risk of bias. The
      reporting of outcome data was inconsistent. No differences were found between
      treatment and control groups except in one study that found a difference between
      individual cognitive behavioural therapy and treatment as usual. CONCLUSION: The
      evidence regarding effective interventions for adolescents and young adults with
      suicide attempt, deliberate self-harm or suicidal ideation is extremely limited.
      Many more methodologically rigorous trials are required. However, in the meantime
      CBT shows some promise, but further investigation is required in order to
      determine its ability to reduce suicide risk among young people presenting to
      clinical services.

PMID- 21174503
TI  - Cognitive dysfunction in post-traumatic obsessive-compulsive disorder.
AB  - OBJECTIVE: To investigate whether patients who develop obsessive-compulsive
      disorder (OCD) after posttraumatic stress disorder, i.e. post-traumatic OCD (PsT
      OCD), display a distinctive neurocognitive pattern of dysfunction. METHODS:
      Patients with PsT-OCD (n = 16), pre-traumatic OCD (PrT-OCD) (n = 18), non
      traumatic OCD (NonT-OCD) (n = 67) and healthy controls (n = 17) had their
      performance compared on the following neuropsychological tests: the Wisconsin
      Card Sorting Test, the Iowa Gambling Task, the Wechsler Memory Scale Logical
      Memory, the Brief Visual Memory Test - Revised, and the Wechsler Abbreviated
      Scale for Intelligence. RESULTS: Patients with OCD, as a group, were
      characterized by poor set-shifting abilities and impaired verbal and visuospatial
      memories. Impaired set-shifting abilities were found to correlate with the
      severity of obsessive-compulsive symptoms in all groups of patients with OCD,
      with the exception of PsT-OCD. Only patients with PsT-OCD were characterized by
      impaired visuospatial recognition, which was found to correlate with poor set
      shifting abilities in this particular group of patients, but not in individuals
      with other types of OCD or in healthy controls. CONCLUSIONS: Our study suggests
      that PsT-OCD is associated with a distinctive pattern of neurocognitive
      dysfunction, thus providing support for a different subtype of OCD.

PMID- 21174504
TI  - Controlling the radiation dose received by patients undergoing cardiac imaging.

PMID- 21174506
TI  - After FRANCIS: next steps in the clinical evaluation of varespladib methyl.
AB  - Secretory phospholipase A(2) (sPLA(2)) represents a family of isoenzymes that
      participate in lipoprotein and inflammatory pathways, mediate atherosclerosis and
      enhance myocardial ischemic injury. The Fewer Recurrent Acute Coronary Events
      with Near-term Cardiovascular Inflammatory Suppression (FRANCIS) trial
      (NCT00743925) was a Phase II trial designed to examine the effects of varespladib
      methyl, a small-molecule inhibitor of sPLA(2), on plasma biomarkers in patients
      with acute coronary syndrome (ACS) who were treated with atorvastatin 80 mg and
      standard-of-care daily. Varespladib methyl significantly reduced low-density
      lipoprotein cholesterol and inflammatory biomarkers in ACS subjects treated with
      standard-of-care and atorvastatin 80 mg daily. There was a nonsignificant
      reduction in major adverse cardiovascular events at study completion; however,
      positive trends remained for unstable angina and myocardial infarction. In order
      to achieve the widespread use of varespladib methyl in ACS patients, completion
      of a prospective, randomized placebo-controlled trial in ACS patients and stable
      coronary artery disease patients with increased sPLA(2) activity will be
      required.

PMID- 21174508
TI  - Cardiomyocyte transverse tubule loss leads the way to heart failure.
AB  - Evaluation of: Wei S, Guo A, Chen B et al.: T-tubule remodeling during transition
      from hypertrophy to heart failure. Circ. Res. 107(4), 520-531 (2010). The highly
      organized transverse (T)-tubule membrane system in ventricular myocytes plays an
      integral role in excitation-contraction coupling, and disruption of this T-tubule
      network has been implicated in contractile dysfunction in heart failure. Wei and
      colleagues used advanced confocal imaging techniques to evaluate cardiomyocyte
      membrane structure in intact rat hearts following surgically induced pressure
      overload, and demonstrated a loss of integrity of the T-tubule system.
      Importantly, this T-tubule dropout was detected early in the disease process, at
      the stage of compensated hypertrophy before observable ventricular dysfunction,
      and then progressed in proportion to the severity of the systolic dysfunction.
      These findings provide a new insight into the critical transition from
      compensated hypertrophy to heart failure and suggests important future areas for
      investigation.

PMID- 21174507
TI  - Bosentan for the treatment of adult pulmonary hypertension.
AB  - Pulmonary hypertension is a severe progressive disease with a marked morbidity
      and a high mortality attributed to right heart failure. Bosentan, a dual
      endothelin receptor antagonist, is an effective and well-tolerated oral therapy
      for the management of pulmonary arterial hypertension (PAH; WHO group 1 pulmonary
      hypertension). Bosentan improves cardiopulmonary hemodynamics, exercise capacity,
      WHO functional class and quality of life, as well as delaying time to clinical
      worsening in patients with PAH. This article reviews the role of endothelin-1 in
      the pathogenesis and progression of PAH, the diagnosis of PAH and the
      pharmacology of bosentan, and summarizes the current available evidence for the
      safety and efficacy of bosentan for the treatment of PAH as a monotherapy and
      combination therapy, as well as its role in the management of other forms of
      pulmonary hypertension.

PMID- 21174509
TI  - beta-blockers and their mortality benefits: underprescribed in heart failure and
      chronic obstructive pulmonary disease.
AB  - This article discusses the most recent insights into the actions of beta-blockers
      on the heart and lungs, highlighting that beta-blockers should have a place in
      the treatment of patients with chronic obstructive pulmonary disease (COPD),
      especially in those with coexisting cardiovascular disease or arterial
      hypertension. Practical studies clearly show underutilization of beta-blockers in
      patients with heart failure and COPD, which seems to be caused by an unnecessary
      fear for adverse effects on the lungs, and the 'outdated' adverse effects
      mentioned on instruction leaflets.

PMID- 21174510
TI  - Ordering a cardiopulmonary exercise test for your patient: key considerations for
      the physician.
AB  - Cardiopulmonary exercise testing (CPX) is a specialized exercise assessment that
      provides valuable information in a number of patient populations. Physicians are
      often familiar with standard exercise testing procedures (i.e., the cardiac
      stress test) and, therefore, appropriately refer patients with signs/symptoms
      suggestive of myocardial ischemia. However, the procedures surrounding referral
      for CPX, and the relevance of the data obtained, may not be as widely understood
      in the medical community. The purpose of the current special report is to provide
      physicians referring patients for CPX with information on the appropriateness of
      CPX referral and testing logistics, the identification of an appropriate CPX
      laboratory for referral, and definitions on key CPX variables that should be
      included in the final report.

PMID- 21174511
TI  - Beating-heart valve surgery: is the introduction of lung perfusion/ventilation
      the next step?
AB  - Myocardial and pulmonary ischemia during cardiopulmonary bypass has been
      associated with postoperative cardiac and pulmonary dysfunction, as well as poor
      outcomes. Beating-heart valve surgery utilizing continuous coronary perfusion
      with warm oxygenated blood via the antegrade/retrograde routes, is a novel
      strategy for myocardial protection. Conceptually, it is proposed that maintenance
      of pulmonary perfusion and ventilation during the cardiopulmonary bypass period
      also might be advantageous. The most current evidence regarding these evolving
      techniques and further areas of research are discussed in this article.

PMID- 21174512
TI  - Risk of adverse events after coronary artery bypass graft and subsequent
      noncardiac surgery.
AB  - AIMS: Coronary artery bypass grafts (CABGs) are increasingly performed in elderly
      patients. Risk factors and outcomes are poorly described for those undergoing
      noncardiac surgery within 1 year after CABG. Our objectives were to assess the
      risk and predictors of major adverse events associated with noncardiac surgery
      within 1 year after CABG. METHODS: In a retrospective review of medical records
      at Mayo Clinic (Rochester, MN, USA), over a period of 5 years, we identified
      patients who underwent noncardiac procedures within 1 year post-CABG. All events
      that occurred within 30 days after noncardiac surgery and deaths within 1 year
      after noncardiac surgery were considered to be related to CABG. RESULTS: We
      identified 211 patients; of these, 21 patients had 24 adverse events. Within 1
      year, 11 died, and within the first 30 days, three myocardial infarctions, six
      acute congestive heart failure episodes, three cerebrovascular accidents and one
      deep vein thrombosis episode had occurred. Predictors of an adverse event
      included emergency operation (odds ratio: 6.8), ejection fraction less than 45%
      (p < 0.001) and elevated right ventricular systolic pressure by 40 mmHg or more
      (p = 0.03). After the noncardiac procedure, patients requiring dialysis (p =
      0.02), ventilatory support (p = 0.03) and longer hospital stay (p = 0.03) had
      greater rates of adverse outcomes. CONCLUSION: Post-CABG, preoperative ejection
      fraction less than 45%, right ventricular systolic pressure of 40 mmHg or more,
      as well as emergent noncardiac surgery, were predictors of adverse outcomes after
      the noncardiac procedure. Longer postoperative hospital stay, dialysis, as well
      as ventilatory support, were predictors of adverse outcomes after CABG.

PMID- 21174513
TI  - Current developments in the tissue engineering of autologous heart valves: moving
      towards clinical use.
AB  - The use of tissue-engineering methods to create autologous heart valve constructs
      has the potential to overcome the fundamental drawbacks of more traditional valve
      prostheses. Traditional mechanical valves, while durable, increase the risk for
      endocarditis and thrombogenesis, and require the recipient to continue lifelong
      anticoagulant therapy. Homograft or xenograft heart valve prostheses are
      associated with immune reaction and progressive deterioration with limited
      durability. Most importantly, neither option is capable of growth and remodeling
      in vivo and both options place the patient at risk for valve-related
      complications and reoperation. These shortcomings have prompted the application
      of tissue-engineering techniques to create fully autologous heart valve
      replacements. Future clinically efficacious tissue-engineered autologous valves
      should be nonthrombogenic, biocompatible, capable of growth and remodeling in
      vivo, implantable with current surgical techniques, hemodynamically perfect,
      durable for the patient's life and most importantly, significantly improve
      quality of life for the patient. In order to meet these expectations, the nature
      of the ideal biochemical milieu for conditioning an autologous heart valve will
      need to be elucidated. In addition, standardized criteria by which to
      quantitatively evaluate a tissue-engineered heart valve, as well as noninvasive
      analytical techniques for use in long-term animal models, will be required. This
      article highlights the advances, challenges and future clinical prospects in the
      field of tissue engineering of autologous heart valves, focusing on progress made
      by studies that have investigated a fully autologous, tissue-engineered pulmonary
      valve replacement in vivo.

PMID- 21174514
TI  - Stem cells in cardiac repair.
AB  - Myocardial infarction is the leading cause of death among people in
      industrialized nations. Although the heart has some ability to regenerate after
      infarction, myocardial restoration is inadequate. Consequently, investigators are
      currently exploring the use of human embryonic stem cells (hESCs), skeletal
      myoblasts and adult bone marrow stem cells to limit infarct size. hESCs are
      pluripotent cells that can regenerate myocardium in infarcted hearts, attenuate
      heart remodeling and contribute to left ventricle (LV) systolic force
      development. Since hESCs can form heart teratomas, investigators are
      differentiating hESCs toward cardiac progenitor cells prior to transplantation
      into hearts. Large quantities of hESCs cardiac progenitor cells, however, must be
      generated, immune rejection must be prevented and grafts must survive over the
      long term to significantly improve myocardial performance. Transplanted
      autologous skeletal myoblasts can survive in infarcted myocardium in small
      numbers, proliferate, differentiate into skeletal myofibers and increase the LV
      ejection fraction. These cells, however, do not form electromechanical
      connections with host cardiomyocytes. Consequently, electrical re-entry can occur
      and cause cardiac arrhythmias. Autologous bone marrow mononuclear cells contain
      hematopoietic and mesenchymal stem cells. In several meta-analyses, patients with
      coronary disease who received autologous bone marrow cells by intracoronary
      injection show significant 3.7% (range: 1.9-5.4%) increases in LV ejection
      fraction, decreases in LV end-systolic volume of -4.8 ml (range: -1.4 to -8.2 ml)
      and reductions in infarct size of 5.5% (-1.9 to -9.1%), without experiencing
      arrhythmias. Bone marrow cells appear to release biologically active factors that
      limit myocardial damage. Unfortunately, bone marrow cells from patients with
      chronic diseases propagate poorly and can die prematurely. Substantial challenges
      must be addressed and resolved to advance the use of stem cells in cardiac repair
      including identifying the optimal stem cell(s) that permit transplantation
      without requirements for host immune suppression; timing of stem cell
      transplantation that maximizes chemoattraction of stem cells to infarcts; and
      determining the optimal technique for injecting stem cells for cardiac repair.
      Techniques must be developed to enhance survival and propagation of stem cells in
      the myocardium. These studies will require close cooperation and interaction of
      scientists and clinicians. Cell-based cardiac repair in the 21st century will
      offer new hope for millions of patients worldwide with myocardial infarctions
      who, otherwise, would suffer from the relentless progression of heart disease to
      heart failure and death.

PMID- 21174515
TI  - Anemia in heart failure: an overview of current concepts.
AB  - Chronic heart failure is a substantial public health problem. Anemia is an
      important comorbidity frequently observed in patients with the disease and, in
      heart failure, anemia has only recently started to attract systematic
      epidemiological and therapeutical research endeavor. This article describes the
      many aspects of anemia in chronic heart failure, starting with the ongoing
      discussion of how to define anemia, which has important consequences for the
      estimation of its prevalence and incidence. Further, we discuss prognostic
      implications of anemia in patients with chronic or acute heart failure, the
      etiology of anemia in heart failure and treatment possibilities. Such therapeutic
      avenues embrace intravenous iron preparations and subcutaneous administration of
      erythropoietin and its derivatives, all of which have been extensively studied
      over the last several years. Finally, this article describes the potential costs
      incurred by treating anemic patients with heart failure.

PMID- 21174517
TI  - General practitioners' report of continuous deep sedation until death for
      patients dying at home: a descriptive study from Belgium.
AB  - BACKGROUND: Palliative sedation is increasingly used at the end of life by
      general practitioners (GPs). OBJECTIVES: To study the characteristics of one type
      of palliative sedation, 'continuous deep sedation until death', for patients
      dying at home in Belgium. METHODS: SENTI-MELC, a large-scale mortality follow
      back study of a representative surveillance network of Belgian GPs was conducted
      in 2005-2006. Out of 415 non-sudden home deaths registered, we identified all 31
      cases of continuous deep sedation until death as reported by the GPs. GPs were
      interviewed face-to-face about patient characteristics, the decision-making
      process and characteristics of each case. RESULTS: 28 interviews were conducted
      (response rate 28/31). 19 patients had cancer. 19 patients suffered persistently
      and unbearably. Pain was the main indication for continuous deep sedation (15
      cases). In 6 cases, the patient was competent but was not involved in decision
      making. Relatives and care providers were involved in 23 cases and 18 cases,
      respectively. Benzodiazepines were used in 21 cases. During sedation, 11/28 of
      patients awoke, mostly due to insufficient medication. In 13 cases, the GP
      partially or explicitly intended to hasten the patient's death. CONCLUSION:
      Continuous deep sedation until death, as practiced by Belgian GPs, is in most
      cases used for patients with unbearable suffering. Competent patients are not
      always involved in decision making while in most cases, the patient's family is.

PMID- 21174519
TI  - A new approach to quantifying lung damage after stereotactic body radiation
      therapy.
AB  - Radiological pneumonitis and fibrosis are common after stereotactic body
      radiotherapy (SBRT) but current scoring systems are qualitative and subjective.
      We evaluated the use of CT density measurements and a deformable registration
      tool to quantitatively measure lung changes post-SBRT. Material and methods. Four
      dimensional CT datasets from 25 patients were imported into an image analysis
      program. Deformable registration was done using a B-spline algorithm (VelocityAI)
      and evaluated by landmark matching. The effects of respiration, contrast, and CT
      scanner on density measurements were evaluated. The relationship between density
      and clinician-scored radiological pneumonitis was assessed. Results. Deformable
      registration resulted in more accurate image matching than rigid registration. CT
      lung density was maximal at end-expiration, and most deformation with breathing
      occurred in the lower thorax. Use of contrast increased mean lung density by 18
      HU (range 16-20 HU; p = 0.004). Diagnostic scans had a lower mean lung density
      than planning scans (mean difference 57 HU in lung contralateral to tumor; p =
      0.048). Post-treatment CT density measurements correlated strongly with clinician
      scored radiological pneumonitis (r = 0.75; p < 0.001). Conclusions. Quantitative
      analysis of changes in lung density correlated strongly with physician-assigned
      radiologic pneumonitis scores. Deformable registration and CT density
      measurements permit objective assessment of treatment toxicity.

PMID- 21174520
TI  - Clinical results from first use of prostate stent as fiducial for radiotherapy of
      prostate cancer.
AB  - PURPOSE: A clinical feasibility study using a removable prostate stent as
      fiducial for image-guided radiotherapy (IGRT) of localized prostate cancer (PC).
      MATERIAL AND METHODS: The study included patients with local or locally advanced
      PC. The clinical target volume (CTV) was outlined on magnetic resonance (MR)
      images co-registered to planning computer tomography (CT) images. Daily online
      IGRT was delivered using the stent as fiducial. Risk of migration was estimated
      using multiple MR. Acute urinary toxicity was scored using the international
      prostate symptom score (IPSS). Late gastro-intestinal (GI) and genito-urinary
      (GU) toxicity was scored using the Radio Therapy Oncology Group (RTOG) score,
      biochemical failure (BF) was defined as an elevation of prostate specific antigen
      (PSA) above nadir plus 2 ng/ml after radiotherapy. RESULTS: One hundred men were
      enrolled in the study. Ninety completed radiotherapy with the stent as fiducial.
      No migration of the stent was seen, but three cases of dislocation of the stent
      to the bladder were observed. Acute urinary toxicity based on IPSS was comparable
      to toxicity in patients who had gold markers (GM) as fiducials. Removal of the
      stent was associated with a high frequency of urinary retention. Late GI and GU
      toxicity and BF were comparable to those of other studies, but longer observation
      time is needed. CONCLUSIONS: This study reports the first clinical results of
      using a prostate stent as fiducial. No migration of the stent observed.
      Dislocation of the stent to the urinary bladder was observed in three cases,
      requiring removal of the stent and insertion of a new fiducial. Acute toxicity
      during radiotherapy evaluated from IPSS was comparable to toxicity in patients
      with GM. Removal of the stent was associated with a high frequency of post
      procedural urinary retention. Late toxicity and BF were comparable to those of
      other studies, though longer observation time is needed.

PMID- 21174521
TI  - Central retinal vein occlusion as the initial manifestation of LHON / MELAS
      overlap syndrome with mitochondrial DNA G13513A mutation--case report and
      literature review.
AB  - BACKGROUND: The aim of this paper is to describe the clinical features and
      molecular findings of a unique case of Leber's hereditary optic neuropathy
      (LHON)/mitochondrial encephalopathy, lactic acidosis and stroke-like episodes
      (MELAS) overlap syndrome presenting as nonischemic central retinal vein occlusion
      (CRVO). METHODS: An 11-year-old Chinese girl presented with sudden onset of
      bilateral blurred vision. The clinical history, imaging studies, and molecular
      analysis results were reviewed. The PubMed and OVID databases were used for
      literature review. RESULTS: Nonischemic CRVO in the subject's right eye and
      tortuosity of small and medium-sized retinal arterioles in the left eye were
      found at initial presentation. Bilateral optic disc pallor was then noted with
      recovery of CRVO. Severe headache and several stroke-like episodes occurred
      subsequently, with elevated lactate levels in serum and cerebrospinal fluid.
      LHON/MELAS overlap syndrome was diagnosed, and mitochondrial DNA sequencing
      revealed G13513A heteroplasmic mutation. Vision was 20/30 in the right eye and
      20/800 in the left eye at the last visit. CONCLUSIONS: Mitochondrial DNA G13513A
      mutation can cause LHON/MELAS overlap syndrome. Nonischemic CRVO is a rare
      manifestation of LHON/MELAS. Atypical findings in cases of LHON should raise the
      suspicion of overlap syndrome or other mitochondrial diseases.

PMID- 21174518
TI  - ALSUntangled No. 8: Low dose naltrexone for ALS.

PMID- 21174522
TI  - Genetic linkage analyses and Cx50 mutation detection in a large multiplex Chinese
      family with hereditary nuclear cataract.
AB  - PURPOSE: The aim of the study was to characterize the underlying mutation in a
      large multiplex Chinese family with hereditary nuclear cataract. METHODS: A 6
      generation Chinese family having hereditary nuclear cataract was recruited and
      clinically verified. Blood DNA samples were obtained from 53 available family
      members. Linkage analyses were performed on the known candidate regions for
      hereditary cataract with 36 polymorphic microsatellite markers. To identify
      mutations related to cataract, a direct sequencing approach was applied to a
      candidate gene residing in our linkage locus. RESULTS: A linkage locus was
      identified with a maximum 2-point LOD score of 4.31 (recombination fraction = 0)
      at marker D1S498 and a maximum multipoint LOD score of 5.7 between markers
      D1S2344 and D1S498 on chromosome 1q21.1, where the candidate gene Cx50 is
      located. Direct sequencing of Cx50 showed a 139 G to A transition occurred in all
      affected family members. This transitional mutation resulted in a replacement of
      aspartic acid by asparagine at residue 47 (D47N) and led to a loss-of-function of
      the protein. CONCLUSIONS: The D47N mutation of Cx50 causes the hereditary nuclear
      cataract in this family in an autosomal dominant mode of inheritance with
      incomplete penetrance.

PMID- 21174523
TI  - Myocilin mt.1 gene promoter single nucleotide polymorphism (-1000C>G) in
      Brazilian patients with primary open angle glaucoma.
AB  - BACKGROUND: The myocilin (MYOC) gene promoter polymorphism -1000C>G (MYOC mt.1)
      can be associated with faster progression of primary open angle glaucoma (POAG).
      The purpose of this study was to investigate the MYOC mt.1 in Brazilian patients
      with POAG and to evaluate its possible role on the phenotype and the severity of
      the disease. MATERIAL AND METHODS: One hundred sixty-seven POAG patients and 130
      normal controls were enrolled. DNA samples were prepared and the MYOC mt.1
      polymorphism was screened by real-time polymerase chain reaction (RT-PCR) in an
      Single-nucleotide polymorphism (SNP) assay. Frequencies of the MYOC mt.1 promoter
      polymorphism were determined for both groups and compared by Fisher's exact test
      and Chi-square test with Yate's correction. Intraocular pressure (IOP), cup-to
      disc ratio (C/D), number of glaucoma medications, and number of glaucoma
      surgeries were compared between MYOC mt.1 carriers and non-carriers. RESULTS:
      MYOC mt.1 genotype frequencies did not differ between POAG and controls (P  = 
      0.420); 14.6% of controls and 16.4% of POAG patients were MYOC mt.1 carriers (CG
      or GG). Frequencies of the G allele were similar between glaucomatous patients
      and controls (7.3% and 9.2%, respectively; P  =  0.477). Among POAG patients,
      there were no differences in mean C/D ratio, IOP, number of glaucoma medications,
      and surgical procedures for IOP control between carries and non-carriers of the
      MYOC mt.1 promoter polymorphism (p>0.05). CONCLUSION: The G allele of the MYOC
      mt.1 promoter polymorphism was equally distributed among POAG patients and
      healthy subjects and it is possibly unrelated to the risk and severity of disease
      in the Brazilian population.

PMID- 21174524
TI  - Juvenile xanthogranuloma of the corneoscleral limbus: report of two cases.
AB  - PURPOSE: To report the clinical and histopathologic findings of limbal juvenile
      xanthogranuloma (JXG) in two children. METHODS: Case report. RESULTS: Two
      children (a 9-month old boy and a 4-year old girl) presented with an enlarging
      yellowish mass at the corneoscleral limbus. The girl had been diagnosed with
      neurofibromatosis 1 (NF1). Both lesions underwent simple excision.
      Histopathologic examination revealed foamy histiocytes within an inflammatory
      infiltrate with the presence of multiple multinucleated giant cells. In both
      cases intraoperative subconjunctival steroids and postoperative topical steroids
      were administered during 1 month. CONCLUSIONS: Juvenile xanthogranuloma may
      rarely present as a mass occurring at the corneoscleral limbus. Therefore it
      should be considered in the differential diagnosis of any corneoscleral limbal
      mass lesion, particularly in children. Most are isolated lesions without systemic
      involvement which are treated by simple excision. But association with NF1 is
      possible and in that case screening for hematological malignancies is
      recommended.

PMID- 21174525
TI  - RPGR: role in the photoreceptor cilium, human retinal disease, and gene therapy.
AB  - Cilia are specialized dynamic organelles extending from the surface of almost all
      mammalian cells. Since proteins and protein precursors are transported across the
      ciliary compartments via intraflagellar transport (IFT), mutations in genes
      encoding proteins that participate in IFT can cause a spectrum of different
      ciliopathies. Photoreceptors of the mammalian retina contain ciliary structures
      that connect the inner (IS) with the outer segments (OS). This structure, the
      connecting cilium (CC), serves as the only junction between OS and IS, the
      correct passage of proteins through the CC is crucial for the functioning and
      maintenance of the cells. Therefore, any impairment of the IFT leads to severe
      malfunction of photoreceptors, and may induce apoptosis ultimately leading to the
      degeneration of the retina. The Retinitis Pigmentosa GTPase Regulator (RPGR),
      which is located in the CC, participates in the IFT and interacts with a variety
      of proteins, including RPGRIP-1, CEP290, NPM, SMC1 and 3 and IFT88. However, the
      function of RPGR through its interaction with these proteins is not yet entirely
      understood. Mutations in the RPGR gene lead to X-linked Retinitis pigmentosa
      (XLRP), one of the most severe and early onset forms of RP. Gene therapy is
      considered a potential therapeutic option and is currently under investigation in
      several animal models of XLRP. However, some of the currently available mouse
      models are only partially suitable for the development of therapeutic strategies
      and the quest for more appropriate small animal models is still an issue.

PMID- 21174526
TI  - Ocular manifestations in hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber
      disease): a case-series.
AB  - BACKGROUND: Hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease) is
      an autosomal dominant vascular disorder characterized by severe and recurrent
      nosebleeds, muco-cutaneous telangiectasias, and, in some cases, life-threatening
      visceral arteriovenous malformations. Ocular abnormalities include conjunctival
      telangiectasia, arteriovenous fistula, angiectasia, phlebectasia, and angioma.
      MATERIAL AND METHODS: We describe the ocular abnormalities in 8 patients from a
      pedigree with hereditary hemorrhagic telangiectasia. This article also reviews
      and discusses the relevant literature. RESULTS: Five patients (62.5%) had
      conjunctival telangiectasias and 3 (37.5%) retinal abnormalities, consisting
      mainly of choriocapillaris atrophy. CONCLUSIONS: To the best of our knowledge,
      this is the first report describing the occurrence of choriocapillaris atrophy in
      patients affected by hereditary hemorrhagic telangiectasia and belonging to the
      same pedigree.

PMID- 21174527
TI  - Giant macular hole in Alport syndrome.

PMID- 21174528
TI  - Evaluation of the in vitro differential protein adsorption patterns of didanosine
      loaded nanostructured lipid carriers (NLCs) for potential targeting to the brain.
AB  - The preferential in vitro adsorption of apolipoprotein E (Apo E) onto the surface
      of colloidal drug carriers may be used as a strategy to evaluate the in vivo
      potential for such systems to transport drugs to the brain. The aim of this
      research was to investigate the in vitro protein adsorption patterns of
      didanosine-loaded nanostructured lipid carriers (DDI-NLCs), using two-dimensional
      polyacrylamide gel electrophoresis (2-D PAGE), in order to establish the
      potential for NLCs to deliver DDI to the brain. NLC formulations were
      manufactured using high-pressure homogenization using a lipid matrix consisting
      of a mixture of Precirol((r)) ATO 5 and Transcutol((r)) HP. The 2-D PAGE analysis
      revealed that NLCs in formulations stabilized using Solutol((r)) HS 15 alone or
      with a ternary surfactant system consisting of Solutol((r)) HS 15, Tween((r)) 80,
      and Lutrol((r)) F68, preferentially adsorbed proteins, such as Apo E. Particles
      stabilized with Tween((r)) 80 and Lutrol((r)) F68 did not adsorb Apo E in these
      studies, which could be related to the relatively large particle size and hence
      small surface area observed for these NLCs. These findings have revealed that DDI
      loaded NLCs may have the potential to deliver DDI to the brain in vivo and, in
      addition, to Tween((r)) 80, which has already been shown to have the ability to
      facilitate the targeting of colloidal drug delivery systems to the brain.
      Solutol((r)) HS 15-stabilized nanoparticles may also achieve a similar purpose.

PMID- 21174529
TI  - A novel nonsense mutation in rhodopsin gene in two Indonesian families with
      autosomal recessive retinitis pigmentosa.
AB  - PURPOSE: To report a novel, identical nonsense mutation in the rhodopsin (RHO)
      gene in two Indonesian families with autosomal recessive retinitis pigmentosa
      (arRP). METHODS: Mutation screening for the RHO gene was performed in 38
      unrelated patients with retinitis pigmentosa (RP) by direct sequencing. Clinical
      features were also characterized, through complete ophthalmologic examination.
      Family members of RP patients testing positive for the RHO gene were subjected to
      genetic and clinical examination. To assess the founder effect in the two
      families, haplotype analysis also was performed. RESULTS: A novel homozygous
      nonsense mutation was detected in two patients by a G to A transition at
      nucleotide position 482 in exon 2 of the RHO gene, resulting in substitution of a
      tryptophan-to-stop at codon 161 (c.482G>A, p.W161X). Examination of family
      members of these 2 patients showed that the affected members were homozygous and
      unaffected carriers were heterozygous for the p.W161X mutation. Haplotype
      analysis revealed that members of the two families carried the same disease
      associated variants in markers (IVS1 RHO and D3S2322). No p.W161X mutations were
      detected in 45 normal Indonesian subjects, nor were any mutations detected in
      exons 1-5 of the RHO gene in the remaining 36 RP patients. CONCLUSION: We
      detected a novel, recessive nonsense mutation (p.W161X) in the RHO gene of two
      families through mutation screening of RHO in 38 Indonesian RP patients.
      Haplotype analysis suggested that p.W161X was the founder mutation.

PMID- 21174531
TI  - Nanocytology for field carcinogenesis detection: novel paradigm for lung cancer
      risk stratification.

PMID- 21174530
TI  - Phenotypes in defined genotypes including siblings with Usher syndrome.
AB  - OBJECTIVE: To characterize visual function in defined genotypes including
      siblings with Usher syndrome. METHODS: Thirteen patients with phenotypically
      different subtypes of Usher syndrome, including 3 families with affected
      siblings, were selected. Genetic analysis and ophthalmological examinations
      including visual fields, full-field electroretinography (ERG), multifocal
      electroretinography (mf ERG), and optical coherence tomography (OCT) were
      assessed. The patients' degree of visual handicap was evaluated by a
      questionnaire (ADL). RESULTS: Twelve of thirteen patients were genotyped as Usher
      1B, 1D, 1F, 2A, 2C or 3A. In 12 of 13 patients examined with ERG the 30 Hz
      flickering light response revealed remaining cone function. In 3 of the patients
      with Usher type 1 mf ERG demonstrated a specific pattern, with a sharp
      distinction between the area with reduced function and the central area with
      remaining macular function and normal peak time. OCT demonstrated loss of foveal
      depression with distortion of the foveal architecture in the macula in all
      patients. The foveal thickness ranged from 159 to 384 um and was not correlated
      to retinal function. Three siblings shared the same mutation for Usher 2C but in
      contrast to previous reports regarding this genotype, 1 of them diverged in
      phenotype with substantially normal visual fields, almost normal OCT and mf ERG
      findings, and only moderately reduced rod and cone function according to ERG.
      CONCLUSIONS: Evaluation of visual function comprising both the severity of the
      rod cone degeneration and the function in the macular region confirm phenotypical
      heterogeneity within siblings and between different genotypes of Usher syndrome.

PMID- 21174533
TI  - Efficacy of bendamustine in rituximab-refractory indolent B-cell non-Hodgkin
      lymphoma: review of a pivotal trial.
AB  - B-cell malignancies, including B-cell non-Hodgkin's lymphoma (NHL) and chronic
      lymphocytic leukemia (CLL), are the most common hematologic malignancies in the
      western world. Although excellent response rates are achieved with standard
      chemoimmunotherapy, patients often relapse and additional treatment is necessary.
      Bendamustine, a unique cytotoxic agent with alkylating and antimetabolite
      properties, has been used for decades in Germany for NHL, CLL and multiple
      myeloma. In 2008, bendamustine was approved by the US FDA for the treatment CLL
      and rituximab-refractory indolent B-cell NHL. The approval in NHL was based on
      the results of this multicenter, single-arm trial in which patients with
      rituximab-refractory indolent NHL received bendamustine 120 mg/m(2) on days 1 and
      2 of each 21-day cycle for six to eight cycles. The primary end points were
      overall response rate and median duration of response, and the secondary end
      points were progression-free survival and the safety profile. Bendamustine
      demonstrated significant efficacy with an overall response rate of 75% median
      duration of response of 9.2 months and median progression-free survival of 9.3
      months, as well as easy tolerability. The most common toxicities were nausea,
      myelosuppression and infection. These results confirm bendamustine's role in
      rituximab-refractory indolent B-cell NHL.

PMID- 21174534
TI  - Cabazitaxel for the treatment of castration-resistant prostate cancer.
AB  - Treatment with docetaxel-based chemotherapy results in improved survival in
      patients with metastatic castration-resistant prostate cancer. However, all
      patients eventually develop progressive disease associated with poor outcomes. In
      this article, we discuss the available second-line therapeutic options following
      docetaxel, with a special focus on cabazitaxel, which is the first agent to yield
      extended survival as second-line therapy following docetaxel. Cabazitaxel, a
      novel semi-synthetic taxane, is effective even in docetaxel-resistant model
      systems. Recently, results of the Phase III TROPIC trial demonstrated improved
      survival with cabazitaxel plus prednisone compared with mitoxantrone and
      prednisone in patients with progressive metastatic castration-resistant prostate
      cancer, following prior docetaxel, which led to approval by the US FDA.

PMID- 21174535
TI  - A global approach to inflammatory breast cancer.
AB  - Inflammatory breast cancer (IBC) is the most aggressive and deadly form of breast
      cancer. In spite of the comprehensive multidisciplinary approach to the
      management of this disease, the prognosis remains dismal. Moreover, there have
      been no major advancements in understanding the etiology and biology of IBC and
      no significant improvements in the diagnosis of the disease. The International
      Inflammatory Breast Cancer Conference was established in 2008 with the intention
      of creating a forum for the discussion, collaboration and development of
      proposals and working hypotheses. Furthermore, the conference represented an
      opportunity to raise awareness regarding IBC. The second international conference
      reported on several new exciting projects based on work from investigators and
      research teams devoted to making a difference in the fight against this disease.

PMID- 21174536
TI  - Electromagnetic navigation bronchoscopy.
AB  - In 2009, lung cancer was estimated to be the second most common form of cancer
      diagnosed in men, after prostate, and the second, after breast cancer, in women.
      It is estimated that it caused 159,390 deaths more than breast, colon and
      prostate cancers combined. While age-adjusted death rates for this cancer have
      been declining since 2000, they remain high.

PMID- 21174537
TI  - Do anthracyclines still have a role in adjuvant chemotherapy of breast cancer?
AB  - Anthracycline-based regimens became the standard of care for early breast cancer
      patients based on the survival advantage they provide over nonanthracycline
      containing regimens. The addition of taxanes, and subsequently trastuzumab in
      HER2-overexpressing patients, to anthracyclines further improved their efficacy
      in several studies involving high-risk early breast cancer patients. Concern over
      toxicity initially surfaced after anthracyclines were reported to carry an
      increased risk of cardiotoxicity and secondary leukemia. Trastuzumab has since
      been shown to compound the risk of cardiotoxicity in patients who have received
      an anthracycline. This has led to the development of regimens featuring a taxane
      without an anthracycline; these protocols vary in design and have different
      toxicity and efficacy profiles. Ongoing investigations are centered on the
      optimization of nonanthracycline regimens, prospective exploration of molecular
      markers to identify populations of patients who will derive maximal benefit from
      anthracycline-based chemotherapy, and the identification of less cardiotoxic
      formulations of existing anthracycline agents. Perhaps most importantly, a
      rapidly growing understanding of the biological heterogeneity of breast cancer is
      likely to lead to an individualized standard of care guided by particular patient
      and tumor characteristics.

PMID- 21174538
TI  - Epigenetic factors in cancer development: polycomb group proteins.
AB  - The role of chromatin-modifying factors in cancer biology emerged exponentially
      in the last 10 years, and increased attention has been focused on Polycomb group
      (PcG) proteins and their enzymatic activities. PcG proteins are repressive
      chromatin modifiers required for proliferation and development. The frequent
      deregulation of PcG activities in human tumors has direct oncogenic effects and
      results, essential for cancer cell proliferation. Here we will review the recent
      findings regarding PcG proteins in prospective tumor development, focusing on the
      molecular mechanisms that deregulate PcG expression in different tumors, at the
      downstream pathways to PcG expression (that contribute to cancer development) and
      at the mechanisms that regulate PcG recruitment to specific targets. Finally, we
      will speculate on the benefit of PcG inhibition for cancer treatment, reviewing
      potential pharmacological strategies.

PMID- 21174539
TI  - RUNX1 translocations and fusion genes in malignant hemopathies.
AB  - The RUNX1 gene, located in chromosome 21q22, is crucial for the establishment of
      definitive hematopoiesis and the generation of hematopoietic stem cells in the
      embryo. It contains a 'Runt homology domain' as well as transcription activation
      and inhibition domains. RUNX1 can act as activator or repressor of target gene
      expression depending upon the large number of transcription factors, coactivators
      and corepressors that interact with it. Translocations involving chromosomal band
      21q22 are regularly identified in leukemia patients. Most of them are associated
      with a rearrangement of RUNX1. Indeed, at present, 55 partner chromosomal bands
      have been described but the partner gene has solely been identified in 21
      translocations at the molecular level. All the translocations that retain Runt
      homology domains but remove the transcription activation domain have a
      leukemogenic effect by acting as dominant negative inhibitors of wild-type RUNX1
      in transcription activation.

PMID- 21174540
TI  - Rectal cancer staging: is there an optimal method?
AB  - The staging process in a newly diagnosed rectal cancer is divided into three
      parts. One essential part is the local staging, in which both endorectal
      ultrasound and MRI are used to disclose the size of the tumor and its correlation
      to the perirectal fascia, and to identify lymph node deposits and vascular
      invasion. This local staging process will guide clinicians to decide upon not
      only the type of surgery (local excision or radical surgery) but also whether or
      not some type of neoadjuvant treatment, such as radiotherapy and/or chemotherapy,
      is indicated. The second part is to evaluate whether or not the tumor has already
      metastasized at diagnosis. The most important organs to evaluate are the liver
      and lungs, and imaging techniques such as ultrasound, CT-scan, or sometimes PET
      CT, and MRI can be used. The third important part is to investigate the rest of
      the large bowel for synchronous adenomas or cancers. This will preferably be done
      with colonoscopy or CT-colonography and sometimes barium enema. This article
      discusses the imaging techniques used for local staging and distant metastases.

PMID- 21174541
TI  - Circulating tumor cells in uveal melanoma.
AB  - Despite advances in the diagnosis and local tumor control, the overall mortality
      rate for uveal melanoma remains high because of the development of metastatic
      disease. The clinical and histopathological systems currently being used to
      classify patients are not sufficiently accurate to predict metastasis. Tumor
      genotyping has demonstrated significant promise but obtaining tumor tissue can be
      problematic. Furthermore, assessment of tumor tissue does not indicate whether
      tumor cells have actually been shed and cannot indicate whether treatment is
      reducing metastasis. The detection of circulating tumor cells in blood has been
      shown to be a prognostic biomarker that can be used to monitor the effectiveness
      of therapy in patients with metastatic carcinoma. Uveal melanoma disseminates
      hematogenously, and the detection of circulating melanoma cells may potentially
      be useful for diagnosis, risk stratification, and the monitoring of disease
      progression and treatment efficacy. PCR-based and immunomagnetic cell isolation
      techniques, derived from studies in patients with cutaneous melanoma, have been
      tested. For various biological and technical reasons, they have not demonstrated
      the accuracy and reproducibility required for an effective prognostic assay in
      patients with uveal melanoma. Assessments have been confounded by false positives
      and negatives and thus, correlations between circulating melanoma cells and
      survival have not yet been established. Circulating melanoma cell detection is a
      valuable tool for investigating metastasis in uveal melanoma and also has the
      potential to become a standard part of uveal melanoma management. However, more
      research on the biology of uveal melanoma as well as improvements upon the
      current technologies are needed.

PMID- 21174542
TI  - Idiotype vaccine strategies for treatment of follicular lymphoma.
AB  - Follicular lymphoma is an indolent lymphoma associated with a relapsing course.
      Immunization with tumor B cell idiotype (Id; a unique variable region of surface
      B cell immunoglobulin) may induce humoral and cellular immune response against
      the tumor. Based on promising results from early phase clinical trials with Id
      vaccine, three Phase III trials were initiated, which, despite failing to meet
      their primary end points, still provided a glimmer of optimism. This article
      describes the clinical development of the Id vaccine against follicular lymphoma,
      outlines the outcomes of clinical trials and delineates the future prospects for
      the integration of the idiotype vaccine into follicular lymphoma treatment.

PMID- 21174543
TI  - Role of IKKalpha in skin squamous cell carcinomas.
AB  - Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are two major types
      of skin cancer derived from keratinocytes. SCC is a more aggressive type of
      cancer than BCC in humans. One significant difference between SCC and BCC is that
      SCC development is generally associated with cell dedifferentiation and
      morphological changes. When SCC is converted to spindle cell carcinoma, the
      latest stage of cancer, the tumor cells change to a fibroblastic cell morphology
      (epithelial-to-mesenchymal transition) and lose their differentiation markers.
      Recently, several laboratories have reported altered IkappaB kinase alpha
      (IKKalpha) protein localization, downregulated IKKalpha, and IKKalpha gene
      deletions and mutations in human SCCs of the skin, lung, esophagus, and neck and
      head. In addition, IKKalpha reduction promotes chemical carcinogen- and
      ultraviolet B-induced skin carcinogenesis, and IKKalpha deletion in keratinocytes
      causes spontaneous skin SCCs, but not BCCs, in mice. Thus, IKKalpha emerges as a
      bona fide skin tumor suppressor. In this article, we will discuss the role of
      IKKalpha in skin SCC development.

PMID- 21174544
TI  - Novel agents to improve outcome of allogeneic transplantation for patients with
      multiple myeloma.
AB  - Over the last few decades therapy for multiple myeloma has improved remarkably.
      In particular, the introduction of novel agents has allowed improved response
      rates prior to, and after, stem cell transplantation with extension of
      progression-free survival in high-risk patients. Nevertheless, most patients
      relapse, leaving multiple myeloma an incurable disease. Despite being the only
      treatment option that has real curative potential, allogeneic transplantation has
      not shown its superiority to autologous transplantation due to its high morbidity
      and mortality rates. This review highlights how novel agents might help to reduce
      treatment-related mortality and to improve tumor control prior to and post
      allogeneic stem cell transplant, which will hopefully result in significantly
      improved long-term disease control, and maybe a cure following this treatment
      modality.

PMID- 21174548
TI  - Importance of motivation to children's participation: a motivation to change.

PMID- 21174545
TI  - Stereotactic body radiation therapy for adrenal metastases: a retrospective
      review of a noninvasive therapeutic strategy.
AB  - AIMS: The role of radiation therapy in the treatment of adrenal metastases has
      traditionally been a palliative one, achieving excellent pain control with very
      limited toxicity. Recent studies have focused on the potential role of
      stereotactic body radiation therapy (SBRT) with curative intent in limited
      metastatic disease, its potential to reduce tumor burden and to prevent
      symptomatic progression. This study reports the single-institution outcomes of
      SBRT utilizing both single fraction and hypofractionated regimens in the
      treatment of adrenal metastases. METHODS: A total of seven patients with nine
      adrenal metastases treated with SBRT at the University of Pittsburgh Cancer
      Institute were retrospectively studied. The primary malignancies consisted of non
      small-cell lung cancer (n = 4), small-cell lung cancer (n = 1) and hepatocellular
      carcinoma (n = 2). RESULTS: Five lesions were treated in a single fraction to a
      median prescription dose of 16 Gy (range: 10-22 Gy) to the 80% isodose line. The
      remaining four lesions were treated over three fractions to a median prescription
      dose of 27 Gy (range: 24-36 Gy), with a median prescription isodose line of 94%
      (range: 80-94%). Median follow-up from the primary diagnosis was 38 months
      (range: 7-88 months) and from SBRT was 14 months (range: 1-60 months). Follow-up
      imaging for six patients, and eight metastatic lesions, revealed one complete
      response, two partial responses and five stable lesions. Five of the lesions
      eventually failed locally, with a median time to failure of 12 months and
      actuarial local control of 63% at 1 year. The median overall survival was 8
      months from SBRT. CONCLUSION: SBRT can be safely delivered in single fraction, or
      hypofractionated, regimens for the treatment of adrenal metastases.

PMID- 21174549
TI  - Immunomodulatory properties of anticancer monoclonal antibodies: is the 'magic
      bullet' still a reliable paradigm?

PMID- 21174550
TI  - News & views in ... Immunotherapy.

PMID- 21174551
TI  - Sublingual immunotherapy and oral mucosal langerhans cells.

PMID- 21174552
TI  - Conference scene: miniaturisation - micro scale bioprocess development.
AB  - The Miniaturisation - Micro Scale Bioprocess Development conference organized by
      Euroscicon hosted 44 delegates from the UK, Germany and Switzerland. The aim of
      the meeting was to highlight the recent technologies used in high-throughput
      bioprocess development, ranging from the selection of clones through to the
      analysis of the final product and formulation. Expert speakers discussed the
      development and use of up-to-date miniaturization technologies and the regulatory
      hurdles that must be overcome to expedite a wider industrial uptake. The meeting
      was chaired by Gary Lye (University College London, UK). Lye gave a detailed
      introduction to the meeting, ending with a talk and a summation at the close of
      the conference.

PMID- 21174553
TI  - Immunologic therapy targeting metastatic melanoma: allovectin-7.
AB  - In the USA, the incidence of cutaneous melanoma is increasing rapidly. It has
      been shown to be responsive to immune-stimulating drugs. Allovectin-7 allows the
      immune system to recognize metastatic melanoma lesions as foreign by
      incorporating a MHC class I complex into the tumor through direct injection. Once
      transfected, tumor biopsies have shown an increased presence of cytotoxic T
      lymphocytes in the tumor beds themselves. Phase I and II trials have shown local
      and systemic response to these tumors, with an excellent safety profile.
      Currently, a Phase III trial has completed enrollment and is set to determine the
      safety and efficacy of treatment in comparison with standard chemotherapy.

PMID- 21174554
TI  - Defining the mechanisms of CD8 T-cell tumor tolerance.
AB  - CD8 T-cell inhibition by myeloid-derived suppressor cells (MDSCs) is one of the
      presumed methods by which tumors evade the immune system, although the mechanism
      remains unclear. This paper provides a new insight into the inhibitory
      interactions between MDSCs and T cells and the mechanisms by which this occurs.
      The authors demonstrated that tumor-mediated CD8 T-cell suppression via MDSCs
      causes T cells to be suppressed only for the T-cell receptor (TCR) specific for
      the tumor-derived antigen while remaining responsive to antigens activating other
      TCRs in the same cell. They further show that the specific TCR complex is
      nitrated by the MDSC, which reduces the physical interaction of TCRs with CD3zeta
      and CD8 and results in lower levels of several TCR-related molecules, including
      phosphorylated CD3zeta, and reduces activation, proliferation and IFN-gamma
      production in response to the specific antigen of the TCR only. This article will
      move the field of tumor immunology forward by identifying potential therapeutic
      targets as well as advancing a mechanistic knowledge to guide further research.

PMID- 21174555
TI  - Therapeutic cancer vaccine fulfills the promise of immunotherapy in prostate
      cancer.
AB  - For many years, preclinical and clinical studies have attempted to harness the
      power of the immune system and focus it on malignant cells in an attempt to
      improve clinical outcomes for patients with cancer. This paper describes the
      landmark Phase III trial that led to the first US FDA approval of a therapeutic
      cancer vaccine. In a randomized trial of 512 patients, those treated with
      sipuleucel-T survived for 25.8 months compared with those treated with placebo,
      who survived 21.7 months (HR: 0.78; p = 0.03). There was, however, no change in
      time to progression, which may relate to the underlying mechanism of this new
      class of therapeutics.

PMID- 21174556
TI  - Enhancing the specificity of T-cell cultures for adoptive immunotherapy of
      cancer.
AB  - Adoptive immunotherapy is a promising approach for the treatment of cancer;
      however, autoimmunity against normal tissue can be a serious complication of this
      therapy. We hypothesized that T-cell cultures responding maximally only when
      engaging two antigens would be more specific for tumor cells, and less active
      against normal cells, as long as the tumor expressed both antigens, while normal
      cells expressed only one of the antigens. A model system was developed consisting
      of cell lines expressing either folate binding protein or erbB-2, representing
      'normal' tissue, and cells expressing both antigens representing tumor tissue.
      Human T-cell cultures were produced using two chimeric antigen receptor vectors
      ('dual transduced'), or using a single chimeric antigen receptor vector
      (monospecific). Dual-transduced T cells responded less against 'normal' cells
      compared with tumor cells. This relatively simple procedure produced T-cell
      cultures that were as active against a tumor as the monospecific cultures used
      traditionally, but had lower activity against model normal cells.

PMID- 21174557
TI  - Pentapeptide commonality between Corynebacterium diphtheriae toxin and the Homo
      sapiens proteome.
AB  - Cross-reactivity may affect diagnostic tests and cause harmful autoimmune
      reactions following immunotherapy. To predict potential cross-reactivity and
      search for safe immunotherapeutic approaches, we analyzed sequence identity
      between microbial antigens and the human proteome. Using diphtheria toxin (DT) as
      a model, we examined its patterns of identity with human proteins at the
      pentapeptide level. DT shares 503 pentapeptides with the human proteome, while
      only 31 pentapeptides are unique to the toxin. DT pentapeptide identity involves
      multiple/repeated matches in human proteins (a total of 4966 occurrences). Human
      proteins containing bacterial peptide matches include antigens linked to
      fundamental cellular functions, such as cell cycle control, proliferation,
      development and differentiation. The data presented in this article offer a
      rational basis for designing peptide-based vaccines that specifically target DT
      and thus eliminate the potential risk of cross-reactivity with human proteins.
      More generally, this study proposes a methodological approach for avoiding cross
      reactivity in immune reactions.

PMID- 21174558
TI  - Invariant NK T cells: potential for immunotherapeutic targeting with glycolipid
      antigens.
AB  - Invariant NK T (iNKT) cells are a subset of T lymphocytes that recognize
      glycolipid antigens bound with the antigen-presenting molecule CD1d. iNKT cells
      have potent immunoregulatory activities that can promote or suppress immune
      responses during different pathological conditions. These immunoregulatory
      properties can be harnessed for therapeutic purposes with cognate glycolipid
      antigens, such as the marine sponge-derived glycosphingolipid alpha
      galactosylceramide. Preclinical studies have shown substantial promise for iNKT
      cell-based treatments of infections, cancer and autoimmune and inflammatory
      diseases. Translation of these preclinical studies to the clinic, while faced
      with some obstacles, has already had some initial success. In this article, we
      review the immunodulatory activities of iNKT cells and the potential for
      developing iNKT cell-based prophylactic and curative therapies of human disease.

PMID- 21174559
TI  - Cross-talk between tumor and myeloid cells: how to tip the balance in favor of
      antitumor immunity.
AB  - Myeloid differentiation is often disturbed in cancer, leading to reduced
      frequencies of immunostimulatory dendritic cells and an over-representation of
      immunosuppressive immature myeloid cells, granulocytes and macrophages. As a
      result of this skewed myeloid differentiation, a highly immunosuppressive myeloid
      subset becomes prevalent during cancer development; these myeloid-derived
      suppressor cells are also recruited as a collateral to certain protumorigenic
      inflammatory processes, resulting in an effective downregulation of T-cell
      mediated immune surveillance and antitumor immunity. In this article, some of the
      important myeloid cell subsets and mediators involved in cancer-related immune
      suppression are reviewed. Furthermore, cross-talk between tumors and the myeloid
      compartment, and ways in which it can suppress effective cell-mediated immunity,
      are discussed, as well as possible therapeutic approaches to tip the balance in
      favor of antitumor immunity.

PMID- 21174560
TI  - Immunotherapy targeting colon cancer stem cells.
AB  - In the last 10 years, cancer stem cells have interested the scientific community
      because this small tumorigenic population is also associated with tumor
      progression in human patients and specific targeting of cancer stem cells could
      be a strategy to eradicate cancers currently resistant to conventional therapy.
      Clinical studies have recently demonstrated that adding immune therapy to
      chemotherapy has survival benefits in comparison with chemotherapy alone that can
      sensitize tumors to immune cell-mediated killing (e.g., increasing sensitivity of
      tumor cells to subsequent cytotoxicity by T cells via upregulation of death
      receptors DR5 and Fas). However, loss of MHC molecules is often observed in
      cancer cells, rendering tumor cells resistant to CD8 T-cell-mediated
      cytotoxicity. For this reason, we review the role of other T-cell subsets, such
      as gammadelta T and NK cells that are able to efficiently recognize and kill
      tumor cells and that could be used in passive or active immunotherapy in cancer
      stem cell eradication.

PMID- 21174561
TI  - Role of tyrosine kinase inhibitors in tumor immunology.
AB  - Various immune cells are involved in both innate and acquired immunity against
      tumors. NK cells and cytotoxic T lymphocytes play a role as effector cells to
      directly kill tumor cells. On the other hand, antigen-presenting cells,
      particularly dendritic cells, control tumor-specific immune responses. In
      addition, much focus has been paid on the immune regulatory cells in tumor sites,
      including CD4(+)CD25(+) regulatory T cells and myeloid-derived suppressor cells.
      The recent advances in molecular-targeted therapy for cancer have provided small
      molecule kinase inhibitors, which are effective for several hematopoietic
      malignancies as well as solid tumors in the clinical setting. Most drugs
      generally have inhibitory effects on several kinases, including tyrosine kinases,
      which are critical molecules for the survival, proliferation, migration and
      invasion of tumor cells. Since the host immune surveillance against tumors
      affects tumor progression, it is of interest to understand how these molecular
      targeted drugs affect immune function in the tumor-bearing host. Besides this,
      there are emerging findings that myeloid cells could be involved in tumor
      angiogenesis. In this article, we address the role of tyrosine kinase inhibitors
      in tumor immunology by summarizing their effects on myeloid cells, such as
      antigen-presenting cells and regulatory cells, and their role in tumor immunity
      and angiogenesis.

PMID- 21174562
TI  - Immunomodulation in sepsis: state of the art and future perspective.
AB  - Despite advances in supportive care of critically ill patients, sepsis remains an
      important cause of death worldwide. More than 750,000 individuals develop severe
      sepsis in North America annually, with a mortality rate varying between 35 and
      50%. Over recent years, numerous efforts have been committed to understanding the
      pathophysiology of septic syndrome, as well as attempts to intervene in the
      inflammatory cascade with the aim of altering the outcome of the syndrome and to
      improve survival. Not all of these attempts have been successful. Issued
      guidelines by the International Sepsis Forum have incorporated only the use of
      corticosteroids, tight glycemic control and the use of recombinant activated
      protein C as recommendations for the management of the septic patient along with
      the initial resuscitation and infection-site control measures. These strategies
      along, with novel attempts of immunomodulation, are thoroughly reviewed in this
      article.

PMID- 21174564
TI  - Physical therapists' perceptions of providing services to adults with childhood
      onset neuromotor disabilities.
AB  - Adults with childhood-onset neuromotor disabilities face problems accessing
      health care services. There are often challenges finding primary care providers
      or specialized providers, such as physical therapists, who are knowledgeable
      about neuromotor disabilities. The purpose of this study was to determine the
      perceptions of physical therapists regarding (a) barriers to providing therapy to
      adults with childhood-onset neuromotor disabilities and (b) resources that would
      be beneficial for improving and/or providing these services. An online
      questionnaire was sent to 1,250 therapists licensed in Oregon and Southwest
      Washington. One hundred fifty-two physical therapists responded resulting in a
      12% response rate. The top three barriers to providing therapy were extra time
      for complex patients, lack of insurance coverage, and lack of experience. The
      three most frequently cited resource needs included information on equipment,
      continuing education, and written educational materials. These findings suggest
      that physical therapists may benefit from further education in working with
      adults with childhood-onset neuromotor disabilities.

PMID- 21174565
TI  - Full-disclosure in industry-sponsored laboratory medicine research studies:
      statement by the Consortium of Laboratory Medicine Journal Editors.

PMID- 21174566
TI  - The ADA's new emergency airway course for sedationists.

PMID- 21174568
TI  - Diversity of opioid requirements for postoperative pain control following oral
      surgery--is it affected by polymorphism of the MU-opioid receptor?
AB  - We experience individual differences in pain and sensitivity to analgesics
      clinically. Genetic factors are known to influence individual difference.
      Polymorphisms in the human OPRM1 gene, which encodes the MU-opioid receptors, may
      be associated with the clinical effects of opioid analgesics. The purpose of this
      study was to determine whether any of the 5 common single-nucleotide
      polymorphisms (SNPs) of the OPRM1 gene could affect the antinociceptive effect of
      fentanyl. Fentanyl was less effective in subjects with the G allele of the OPRM1
      A118G SNP than in those with the A allele, and subjects with the G allele
      required more fentanyl for adequate postoperative pain control than those with
      the A allele. In the future, identifying SNPs might give us information to
      modulate the analgesic dosage of opioid individually for better pain control.
      Factors underlying individual differences in sensitivity to pain other than
      genetic factors may include environmental and psychological factors. We therefore
      examined the effects of preoperative anxiety on the analgesic efficacy of
      fentanyl in patients undergoing sagittal split mandibular osteotomy (SSMO). From
      among the patients enrolled in the study, 60 patients (male/female: 18/42, age:
      24.6 +/- 6.7 years) who gave informed consent were examined for correlations
      between preoperative trait/state anxiety, as measured by the state-trait anxiety
      inventory (STAI) on the day before surgery, and postoperative consumption of
      patient-controlled analgesia (PCA) fentanyl and visual analog scale (VAS)
      assessment by patients. Levels of trait and state anxieties measured by the STAI
      were correlated with neither the consumption of PCA fentanyl nor postoperative
      VAS assessment. These findings suggest that psychological factors are unlikely to
      affect postoperative pain or the use of analgesics.

PMID- 21174567
TI  - A prospective, randomized, double-blind comparison of 2% mepivacaine with 1 :
      20,000 levonordefrin versus 2% lidocaine with 1 : 100,000 epinephrine for
      maxillary infiltrations.
AB  - The purpose of this prospective, randomized, double-blind crossover study was to
      compare the anesthetic efficacy of 2% mepivacaine with 1 : 20,000 levonordefrin
      versus 2% lidocaine with 1 : 100,000 epinephrine in maxillary central incisors
      and first molars. Sixty subjects randomly received, in a double-blind manner,
      maxillary central incisor and first molar infiltrations of 1.8 mL of 2%
      mepivacaine with 1 : 20,000 levonordefrin and 1.8 mL of 2% lidocaine with 1 :
      100,000 epinephrine at 2 separate appointments spaced at least 1 week apart. The
      teeth were electric pulp tested in 2-minute cycles for a total of 60 minutes.
      Anesthetic success (obtaining 2 consecutive 80 readings with the electric pulp
      tester within 10 minutes) was not significantly different between 2% mepivacaine
      with 1 : 20,000 levonordefrin and 2% lidocaine with 1 : 100,000 epinephrine for
      the central incisor and first molar. However, neither anesthetic agent provided
      an hour of pulpal anesthesia.

PMID- 21174569
TI  - Nausea, vomiting, and hiccups: a review of mechanisms and treatment.
AB  - Nausea, vomiting, and hiccups are troubling complications associated with
      sedation and general anesthesia. This article will review the basic
      pathophysiology of these events and current recommendations for their prevention
      and management.

PMID- 21174572
TI  - A positive correlation between hydrogen peroxide and soluble TNF-alpha receptor 2
      early in maternal blood and at term in placenta of pregnant women with
      preeclampsia.
AB  - OBJECTIVES: We hypothesized that hydrogen peroxide (H(2)O(2)) and soluble TNF
      alpha receptor 2 (sTNF-R2) co-play a role in the pathogenesis of preeclampsia.
      METHODS: Correlation of H(2)O(2) and sTNF-R2 was assessed in vivo in maternal
      blood and placenta, and in vitro in cytotrophoblasts culture. RESULTS: We showed
      a positive correlation between increased levels of H(2)O(2) and sTNF-R2 early at
      10-15 gestational weeks and at term in maternal serum, and in placenta of women
      with preeclampsia. Our in vitro experiments showed that H(2)O(2) induced the
      placental synthesis of sTNF-R2. CONCLUSION: We propose to consider H(2)O(2) and
      sTNF-R2 as potential biomarkers in predicting preeclampsia.

PMID- 21174573
TI  - Flow-mediated dilatation assessment in women with preeclampsia compared to women
      with gestational hypertension.
AB  - OBJECTIVES: To assess flow-mediated dilatation (FMD) in women with preeclampsia
      (PE) versus gestational hypertension (GH) and to determine if results of this
      ultrasound method vary with modifications to the technique. METHODS: Pregnant
      women with hypertension (BP >= 140/90 mmHg) were recruited. Women were allocated
      to the PE group if they had proteinuria >=300 mg/24 h. FMD(o) was calculated from
      the percentage difference in baseline and post-occlusion (PO) diameter at 45-60 s
      and FMD(max) from baseline and maximum diameter between 45 and 90 s. FMD(max) was
      adjusted for hematocrit and shear rate. RESULTS: FMD(o) (m +/- SD) was similar (p
      = 0.83) in the no medication GH (5.3 +/- 3.2; n = 15) and the PE (6.5 +/- 4.1; n
      = 13) groups. FMD(o) was reduced (p < 0.001) in the medication GH (3.7 +/- 2.8; n
      = 23) versus the PE (8.8 +/- 4.3; n = 25) groups. For FMD(max) the interaction
      between group and medication was not significant (both p = 0.08) in unadjusted
      analysis or analysis adjusted for covariates hematocrit (p = 0.023) and shear
      rate (p = 0.007). Means averaged over medication are presented. FMD(max) was
      reduced (p < 0.0001) in the GH (5.7 +/- 4.0; n = 38) versus the PE group (9.2 +/-
      4.0; n = 38). Of the PE women, 79% (30/38) reached maximum dilatation by 90 s
      compared with 63% (24/38) of the GH women (chi-square, p = 0.16). CONCLUSIONS:
      The FMD(max) analysis revealed reduced FMD in GH women compared with PE women. We
      therefore hypothesize that PE may be a different disease to GH. Our work
      demonstrates differing results in FMD(o) and FMD(max) because of modifications in
      the technique. Previous work on PE and FMD may not be definitive due to this
      evolving technique.

PMID- 21174574
TI  - Adiponectin levels in circulation and breast milk and mRNA expression in adipose
      tissue of preeclampsia women.
AB  - OBJECTIVE: Physiological insulin resistance occurs in normal pregnancy and is
      exaggerated in women with preeclampsia (PE). Adiponectin is a hormone with
      insulin-sensitizing, anti-atherogenic, and anti-inflammatory properties. Reports
      published on association between adiponectin levels and PE risk have been
      conflicting. This study sought to better determine the circulating adiponectin
      levels and its mRNA expression in adipose tissue in women with PE. METHODS: This
      report includes a cross-sectional study at a Chinese clinical research center and
      meta-analysis. The cross-sectional study included normal pregnancy women (n = 28)
      and PE women (n = 20) who underwent cesarean operation. Adiponectin
      concentrations in maternal serum, cord blood, and colostrums were determined by
      ELISA. Adiponectin mRNA expression levels in adipose tissue were measured by
      quantitative real-time PCR. Meta-analysis was done on 13 studies, including 302
      PE women and 385 normal pregnancy women. RESULTS: In comparison with controls, PE
      women had higher serum adiponectin concentrations in maternal blood and breast
      milk, but lower adiponectin concentration in cord blood. Adiponectin mRNA
      expression in the subcutaneous (Sc) and omental adipose tissues (OM) did not
      differ between the two groups of women. Meta-analysis confirms that the
      circulating adiponectin levels were elevated in PE women (p < 0.01). CONCLUSIONS:
      PE women had a higher adiponectin concentration in the maternal blood as well as
      breast milk but lower adiponectin concentration in umbilical cord blood when
      compared to women with normal pregnancy. The elevated circulating adiponectin
      levels in PE women are probably because of a reduced degradation/elimination
      rather than an increased synthesis of this hormone.

PMID- 21174575
TI  - Presentation and outcome of eclampsia at a tertiary center in South East Nigeria-
      a 6-year review.
AB  - OBJECTIVE: To determine the maternal and fetal outcomes of eclamptic patients
      treated in Nnamdi Azikiwe University Teaching Hospital, Nnewi, over a 6-year
      period (2004-2009). MATERIALS AND METHODS: It was a retrospective study. The case
      notes of 212 patients with eclampsia were analyzed with respect to age, parity,
      type of eclampsia, gestational age, booking status, mode of delivery, and outcome
      of the babies and mothers. RESULTS: There were 212 cases of eclampsia out of a
      total of 13,536 deliveries, giving a prevalence of 1.57%. One hundred and sixty
      (24.5%) of the women were unbooked. Antepartum eclampsia constituted 160 (75.5%)
      of all types of eclampsia. Nulliparous teenagers were the most commonly affected
      women--128 (60.4%). Cesarean delivery was higher than vaginal delivery,
      accounting for 160 (75.5%) of all deliveries. There was a statistically
      significant relationship between the route of delivery and the parity of the
      women (chi(2) = 3.60; d = 5; p = 0.035). There were 16 maternal deaths, giving a
      case fatality rate of 7.5%. There were 12 neonatal and 8 perinatal deaths.
      Puerperal sepsis occurred in 9.4% of the patients. CONCLUSION: Eclampsia is a
      major cause of maternal mortality in Nnewi, rural South East Nigeria. Teenage
      nulliparous women are most susceptible.

PMID- 21174576
TI  - HSP70 overexpression in response to ureaplasma urealyticum-mediated oxidative
      stress in preeclamptic placenta.
AB  - OBJECTIVE: To determine the effect of Ureaplasma urealyticum infection on
      oxidative stress during preeclampsia. METHODS: The relationship between oxidative
      stress and U. urealyticum infection was monitored through the estimation of lipid
      hydroperoxidation level (LHP), glutathione redox ratio (GRR), and total
      antioxidant capacity (TAC) along with heat shock protein 70 (HSP70) expression in
      the placenta. Microbial growth analysis was used for U. urealyticum detection.
      RESULTS: U. urealyticum infection was found in 43.7% of the preeclamptic
      subjects. The increased LHP level (p < 0.05) along with decreased GRR (p < 0.05)
      and TAC (p < 0.05) was noted in preeclamptic patients with U. urealyticum
      infection compared with uninfected preeclamptic and normal subjects. Under such
      condition, an increase in the HSP70 levels in the infected preeclamptic samples
      by 24.6% (p < 0.05) on comparison with uninfected preeclamptic samples was
      observed. CONCLUSION: Overexpression of HSP70 in the placental homogenate
      suggests the contribution of infection to oxidative stress development and the
      possible protective role of HSP70 against infection.

PMID- 21174577
TI  - Preeclampsia due to fetal non-immune hydrops: mirror syndrome and review of
      literature.
AB  - OBJECTIVE: Mirror syndrome (Ballantyne's syndrome) refers to the association of
      fetal hydrops and maternal preeclampsia. The aim of this study was to determine
      the relation and incidence between fetal hydrops and preeclampsia in our clinic.
      METHODS: A retrospective review of patients associated with fetal hydrops and
      findings with preeclampsia was used. Seventy-five cases with single pregnancy and
      diagnoses with nonimmune hydrops fetalis were found. According to the data 4
      cases were found related with preeclampsia. RESULTS: Mirror syndrome is rarely
      encountered and underdiagnosed. We found a frequency of 5.3% (4 cases in 75
      affected pregnancies) for single non-immune hydrops cases in which maternal
      hypertension occurred. Fetal outcome is depending on etiology and prognosis is
      mainly very low. Maternal symptoms and laboratory findings are resolving after
      intrauterine fetal death or delivery. CONCLUSION: Hydrops fetalis must be
      considered as a potential risk factor for preeclampsia. It is important that this
      clinical condition has a potential of about 5% for proceeding preeclampsia.

PMID- 21174578
TI  - Comparative study of transabdominal and transvaginal uterine artery Doppler
      pulsatility indices at 11-13 + 6 weeks.
AB  - OBJECTIVE: The objective of this study was to compare two approaches to determine
      the uterine artery pulsatility index (PI) as a screening measure for
      preeclampsia. METHODS: Comparative analysis of the PI values obtained from
      transabdominal and transvaginal Doppler ultrasound in 351 women with singleton
      pregnancies who were examined between May and June 2009 during routine
      morphological study and risk calculation of chromosome anomalies at 11-13 + 6
      weeks of gestation. RESULTS: The mean PI measured transabdominally was 1.83 [95%
      confidence interval (CI) 1.78-1.89], but when measured transvaginally it was 1.98
      (95% CI 1.93-2.08) (p < 0.05). Transabdominal mean PI was observed to decrease as
      the crown-rump length (CRL) increased: 1.96 (95% CI 1.80-2.12) for CRL <60 mm and
      1.71 (95% CI 1.56-1.87) for CRL >=70 mm (p < 0.05). The transvaginally measured
      indices were 2.09 (95% CI 1.93-2.26) and 1.78 (95% CI 1.64-1.92), respectively,
      for the same CRL groups (p < 0.05). A weak correlation was found between the mean
      PI and the mean CRL using Spearman's rho correlation (-0.20 for abdominal
      measures and -0.21 for vaginal measures, p < 0.001). CONCLUSIONS: Transabdominal
      and transvaginal Doppler ultrasound measurements of the uterine artery PI were
      significantly different. The latter approach yielded significantly higher values
      than the first.

PMID- 21174579
TI  - Chronic hypertension and pregnancy at a tertiary-care and university hospital.
AB  - OBJECTIVE: Analyze maternal and perinatal aspects related to chronic hypertension
      (CH) in pregnancy. METHODS: Cross-section and retrospective study. Maternal,
      obstetric, and neonatal variables inserted in a database of the SPSS program,
      version 16.0, were analyzed. Student's t-test was applied to the continuous
      variables and the chi-square test to the dichotomous variables, considering as
      statistically significant a value of p < 0.05. RESULTS: From March 1998 to
      February 2009 about 15,945 births were observed, 888 (5.5%) being related to
      pregnant mothers with CH. In the hypertense group, there was a higher percentage
      of cesarean section, preterm labor during pregnancy, abruptio placentae, small
      for-gestational age babies (<2500 g), and the need for treatment in a neonatal
      intensive care unit (NICU). CONCLUSION: CH in pregnancy was significantly
      associated with maternal age >=30 years, nonwhite race, low level of schooling,
      parity >=3 children, weight gain >=16 kg, greater rates of cesarean section,
      Apgar score at the first and fifth minutes <7, umbilical artery pH <=7.1, fetal
      weight <=2500 g, need for neonatal intensive care, preterm labor during
      pregnancy, abruptio placentae, birth injury, small-for-gestational age babies and
      higher rates of preterm babies, fetal and neonatal mortality. It should be
      emphasized that the variables mentioned are representative or poor birth
      conditions in the group of chronic hypertense pregnant women.

PMID- 21174580
TI  - Protein/creatinine ratio on random urine samples for prediction of proteinuria in
      preeclampsia.
AB  - OBJECTIVE: To evaluate Protein/Creatinine ratio on random urine samples for
      prediction of proteinuria in preeclampsia. MATERIALS AND METHODS: This study was
      performed on 150 pregnant women who were hospitalized as preeclampsia in Ghaem
      Hospital during 2006. At first, a 24-hours urine sample was collected for each
      patient to determine protein/creatinine ratio. Then, 24-hours urine collection
      was analyzed for the evaluation of proteinuria. Statistical analysis was
      performed with SPSS software. RESULTS: A total of 150 patients entered the study.
      There was a significant relation between the 24-hours urine protein and
      protein/creatinine ratio (r = 0.659, P < 0.001). CONCLUSION: Since the
      measurement of protein/creatinine ratio is more accurate, reliable, and cost
      effective, it can be replaced by the method of measurement the 24-hours urine
      protein.

PMID- 21174581
TI  - Genetic variants, endothelial function, and risk of preeclampsia among American
      Indians.
AB  - OBJECTIVE: To determine the prevalence in an American Indian population of
      genetic variants with putative effects on endothelial function and determine
      whether they are associated with preeclampsia. METHODS: Five genetic
      polymorphisms potentially related to endothelial function in the NOS3, GNB3, and
      DDAH1 genes were genotyped from a total of 101 cases, 198 controls, and an
      additional 110 population-based controls among an American Indian population.
      RESULTS: The minor allele frequencies for NOS3 (rs1799983, rs3918227), GNB3
      (rs5442), and DDAH1 (rs10158674, rs233115) among those with and without PE in
      this population were 25, 10, 5, 11, and 30%, respectively. Although not
      statistically significant, the maximum risk associated with any of these SNPs was
      2.22 (0.734-6.73, 95% CI, p = 0.156) in a multivariate analysis of the A allele
      of the rs233115 SNP incorporated in a recessive model. CONCLUSION: Although
      endothelial dysfunction likely plays a role in the pathophysiology of PE, this
      study was unable to find evidence for an association between these five SNPs on
      three genes influencing endothelial function and PE. This may be due to
      insufficient power to detect an association, investigation of SNPs without
      linkage to risk of PE in this population or other factors. Investigation of
      additional SNPs in these or related genes and other populations seems warranted.

PMID- 21174582
TI  - Resibufogenin administration prevents oxidative stress in a rat model of human
      preeclampsia.
AB  - BACKGROUND AND OBJECTIVES: Marinobufagenin (MBG) is a cardiotonic steroid that is
      increased in preeclampsia. An analog of MBG, resibufogenin (RBG), prevents the
      development of preeclampsia in a rat model. Oxidative stress is a concomitant of
      endothelial dysfunction in the latter disorder. The objective of the current
      studies was to evaluate the status of oxidative stress in a rat model of
      preeclampsia. METHODS: We measured the aortic AT(1) receptor expression and
      urinary excretion of 8-isoprostane (8IP) in rats rendered "preeclamptic" and
      compared the findings to those obtained in normal pregnant animals, pregnant rats
      injected with MBG, and preeclamptic rats treated with RBG. RESULTS: Aortic AT(1)
      receptor expression and the urinary excretion of 8IP were significantly augmented
      in "preeclamptic" and MBG-injected pregnant rats compared to normal pregnant
      animals. RBG prevented evidence of oxidative stress in "preeclamptic" rats.
      CONCLUSION: MBG is involved in the causation of oxidative stress in our rat model
      and RBG attenuates this change.

PMID- 21174583
TI  - Preeclamptic angina--a pathognomonic symptom of preeclampsia.
AB  - AIM: To describe an important symptom of preeclampsia previously not defined.
      METHODS: Individual clinician experience case series collected and recorded
      prospectively. RESULTS: Little attention has been given to symptoms in the
      diagnosis of preeclampsia. Although "epigastric pain" is often mentioned, there
      is no accurate description in the literature of the specific diagnostic
      attributes that distinguish the upper abdominal pain of preeclampsia from that of
      other causes. The symptom is described herein and defined as "preeclamptic
      angina" (PEA). It is associated strongly with severe preeclampsia but often not
      recognized, particularly when it is not accompanied by usual features of
      preeclampsia. It is experienced typically as a severe pain that begins at night,
      usually maximal in the low retrosternum or epigastrium, constant and unremitting
      for 1-6 h. It may radiate or be confined to the right hypochondrium or back. The
      liver is tender on palpation. The pain may precede the diagnosis of preeclampsia
      by 7 days or more and may be the only abnormality on presentation such that
      preeclampsia is not suspected. It is of ominous prognosis and is associated with
      a high rate of maternal and fetal complications. Laboratory and clinical
      abnormalities of preeclampsia are ultimately manifest in all cases, but their
      absence at the time of presentation may lead to erroneous alternative diagnoses.
      Recognition of this characteristic symptom will lead to earlier diagnosis of
      preeclampsia in atypical cases, with the potential to avoid maternal and
      perinatal morbidity and mortality.

PMID- 21174584
TI  - Clinical management and outcome of pregnancies complicated by previous abruption.
AB  - OBJECTIVES: We studied the clinical management and prognosis of pregnant women
      with a history of abruption, as well as the associated risk factors. METHODS: We
      reviewed the cases of 23 patients with a history of abruption and 66 patients
      with abruption. RESULTS: The recurrence rate of abruption was 4.3%. Intentional
      care prolonged gestational age in most patients. Although the incidence of
      abruption was low (0.44%), the consequences could be perinatal death and maternal
      disseminated vascular coagulation (DIC). CONCLUSION: To prevent abruption
      recurrence, careful monitoring during hospitalization is important. Both clinical
      findings and transabdominal echography are useful in diagnosing abruption.

PMID- 21174585
TI  - Gestational diabetes or lesser degrees of glucose intolerance and risk of
      preeclampsia.
AB  - OBJECTIVE: We evaluated the association of 1-h oral glucose challenge test (OGCT)
      and 3-h oral glucose tolerance test (OGTT) results with preeclampsia. METHODS: A
      retrospective cohort study was performed among 26,105 women. RESULTS:
      Preeclampsia was associated with the upper OGCT quartiles [114-132 mg/dL: odds
      ratio (OR) = 1.25, 95% confidence interval (CI) 1.09-1.44; >132 mg/dL: OR = 1.40,
      95% CI 1.21-1.61] compared with <98 mg/dL adjusting for age, primigravidity, and
      gestational diabetes, and also to one abnormal OGTT value (adjusted OR 1.38, 95%
      CI 1.09-1.75) or gestational diabetes (adjusted OR 1.45, 95% CI 1.15-1.83).
      CONCLUSION: Higher glucose levels are associated with preeclampsia suggesting a
      pathophysiological role for glucose metabolism.

PMID- 21174586
TI  - Vitamin C and E supplementation does not reduce the risk of superimposed PE in
      pregnancy.
AB  - BACKGROUND: Oxidative stress could play a role in the development of
      preeclampsia. There is some evidence to suggest that vitamin C and E supplements
      can reduce the risk of the disorder. We hypothesized its beneficial role in a
      group of pregnant women with essential hypertension. METHODS: In this randomized
      controlled trial, we enrolled 50 pregnant women with essential hypertension. We
      assigned the women 1000 mg vitamin C and 400 IU natural vitamin E (RRR alpha
      tocopherol; n = 25), daily from the second trimester of pregnancy until delivery
      or no supplementation (n = 25). Our primary endpoint was development of
      superimposed preeclampsia, and main secondary endpoints were aggravation of
      hypertension, need for admission, need to increase antihypertensive drugs, and
      small size for gestational age (<fifth customized birthweight centile). RESULTS:
      We analyzed 50 women who completed the study. The incidence of superimposed
      preeclampsia was similar in vitamin and control groups (8% [n = 2] vs 12% [n =
      3], p = 1.000). Vitamin C and E supplementation also did not prevent aggravation
      of hypertension in group of women who took it (12% [n = 3] vs 32% [n = 8], p =
      0.172). Small size for gestational age babies did not differ between groups (4%
      [n = 2] vs 6% [n = 3], p = 1.000). CONCLUSION: Vitamin C and E supplementation
      does not prevent development of superimposed preeclampsia in women with essential
      hypertension. Our results did not show any significant benefit of vitamin
      supplementation. There was some trend in lessening of hypertensive complications
      of pregnancy. Our results failed to find any correlation between development of
      superimposed preeclampsia and oxidative stress.

PMID- 21174587
TI  - Protein creatinine ratio in random urine sample of hypertensive pregnant women:
      maternal and perinatal outcomes.
AB  - Objective. To compare protein/creatinine ratio (PCR) in random urine sample
      levels and adverse outcomes in hypertensive pregnant women. Methods. A total of
      370 medical charts from hypertensive pregnant women were reviewed and stratified
      into three groups according to different PCR in random urine sample levels (group
      1: PCR < 0.3 mg/mg; group 2: PCR 0.3-1.99 mg/mg; group 3: PCR >= 2.0 mg/mg) and
      compared with composite maternal and perinatal outcomes. Those outcomes were
      severe hypertension, thrombocytopenia, high lactate dehydrogenase count,
      disseminated intravascular coagulation, abruptio placentae, HELLP (hemolysis,
      elevated liver enzymes, low platelet count) syndrome, eclampsia, perinatal death,
      newborn cerebral hemorrhage, respiratory distress syndrome of newborn, neonatal
      sepsis, and newborn small for gestational age. Results. To obtain a composite
      maternal adverse outcome the odds ratio [ORs] between PCR groups were 1.8 (95%
      confidence interval [CI]: 1.1-3.2) between groups 1 and 2, and 3.1 (95% CI: 1.5
      6.3) between groups 1 and 3; for composite perinatal adverse outcomes, the ORs
      were 3.0 (95% CI: 1.5-5.9) between groups 1 and 2, and 3.4 (95% CI: 1.6-7.5)
      between groups 1 and 3. Conclusions. Hypertensive pregnant women with a PCR >=
      0.3 mg/mg, had worse maternal and perinatal outcomes than those with PCR < 0.3
      mg/mg. Above the cut-off of 0.3 mg/mg, higher PCRs are not associated with a
      significant increase in maternal and perinatal morbidity.

PMID- 21174588
TI  - Placental microparticles, DNA, and RNA in preeclampsia.
AB  - Preeclampsia is a common disorder of the second half of pregnancy that
      complicates 2% to 7% of all pregnancies worldwide and remains a major cause of
      maternal and fetal morbidity and mortality. Although the origin of the disease is
      still elusive, population-based studies have suggested that it might implicate
      genetic, immunologic, or physiologic factors. On the other hand, there is no
      doubt that the placenta plays an important role in its development. In
      preeclampsia, the shedding of placenta debris, such as syncytiotrophoblast
      microparticles (STBMs) and DNA and messenger RNA molecules, into the maternal
      peripheral blood is increased. The analysis of this material may give new insight
      into placentation and the underlying etiology of this disorder, as well as yield
      new tracks of research for the understanding of the molecular mechanisms, leading
      to the generation of the clinical symptoms.

PMID- 21174589
TI  - Alternations of maternal and cord plasma hemostasis in preeclampsia before and
      after delivery.
AB  - OBJECTIVE: The aim of this study was to investigate the role of hemostatic
      factors in the pathogenesis of preeclampsia. MATERIALS AND METHODS: Maternal and
      cord plasma concentrations of tissue factor (TF), tissue factor pathway inhibitor
      (TFPI), von willebrand factor (vWF), soluble P-selectin (sP-selectin),
      fibrinopeptide A (FPA), D-dimer, and antithrombin III (AT-III) were measured by
      enzyme-linked immunosorbent assay (ELISA) in 46 women with preeclampsia and 40
      normotensive pregnant women before and after delivery. RESULTS: The maternal
      plasma concentrations of TF, vWF, and sP-selectin were higher, but lower
      concentrations of TFPI, AT-III, and D-dimer were observed in women with
      preeclampsia compared to normotensive pregnant women before and after delivery.
      Compared with maternal plasma, fetal plasma concentrations of TF concentrations
      were increased significantly in both groups, whereas vWF, FPA, TFPI, AT-III, and
      D-dimer were decreased. Compared with normotensive pregnancy, fetal plasma
      concentrations of TF were markedly increased in preeclampsia, accompanied with a
      higher vWF and a lower sP-selectin and D-dimer levels. Furthermore, fetal plasma
      TF concentrations were more significantly increased in women with high blood
      pressure and severe proteinuria. CONCLUSIONS: Imbalance in the
      coagulation/fibrinolysis equilibrium, especially alterations in the extrinsic
      pathway of coagulation and anticoagulation, may play an important role in the
      pathogenesis of preeclampsia. In addition, fetal alteration of TF may be involved
      in the pathogenesis of fetal complications of preeclampsia.

PMID- 21174590
TI  - Endothelin-1 expression by vascular endothelial growth factor in human umbilical
      vein endothelial cells and aortic smooth muscle cells.
AB  - OBJECTIVE: This study investigated endothelin-1 (ET-1) production induced by
      vascular endothelial growth factor (VEGF) in two different vascular wall cell
      types. METHODS: We analyzed the effect of endothelin-converting enzyme-1 (ECE-1)
      inhibitor and tissue inhibitors of matrix metalloproteinase-2 (TIMP-2) on VEGF
      induced ET-1 expression using real-time polymerase chain reaction and enzyme
      linked immunosorbent assay in human umbilical vein endothelial cells and aortic
      smooth muscle cells. RESULTS: In human umbilical vein endothelial cells, both
      phosphoramidon, an inhibitor of ECE-1, and TIMP-2 decreased VEGF-induced ET-1
      production. In aortic smooth muscle cells, TIMP-2 suppressed VEGF-induced ET-1
      production, but phosphoramidon did not influence ET-1 concentration in culture.
      CONCLUSION: VEGF-induced ET-1 production may be MMP-2- or ECE-1-dependant in
      endothelial cells; however, in smooth muscle cells, ET-1 expression appears to be
      induced by MMP-2 only.

PMID- 21174591
TI  - Anxiety and depression in patients with dry eye syndrome.
AB  - PURPOSE: This study aimed to determine whether patients with dry eye syndrome
      [DES] have more symptoms of anxiety and depression than controls without DES.
      METHODS: In this case-control study, the sample consisted of 89 DES subjects (13
      diagnosed with Sjogren's syndrome [SS]) and 73 control subjects. Each subject was
      diagnosed as having DES or was chosen as a control subject by an ophthalmologist.
      The Zung Self Rating Anxiety Scales (SAS), Zung Self Rating Depression Scales
      (SDS), and Ocular Surface Disease Index (OSDI) were administered to all subjects.
      Scores of SAS and SDS, measuring level of anxiety and depression symptoms, were
      compared between the DES group and the control group. Correlations with other
      health status measures were conducted. RESULTS: The SAS and SDS scores of the DES
      group were significantly higher than the control group (P < 0.001, P < 0.001).
      The prevalence of DES subjects with anxiety or depression symptoms was
      significantly higher than in the control group (P = 0.003, P < 0.001). In the DES
      group, SAS scores were found to be correlated with OSDI and educational level.
      SDS scores were found to be correlated with OSDI. Neither SAS nor SDS scores were
      correlated with age, sex, household income, tear break up time (BUT), Schirmer
      Test 1 (S1T), corneal fluorescein staining (FL), or visual acuity. CONCLUSION:
      Anxiety and depression are correlated with DES, demonstrating that DES is an
      important public health problem that merits increased attention and research.

PMID- 21174592
TI  - Ocular surface and dry eye in Graves' disease.
AB  - PURPOSE: To evaluate the tear function tests and the ocular surface damage in
      Graves' disease (GD) patients either with or without thyroid associated
      orbitopathy (TAO). METHODS: Forty-two eyes of 21 randomly selected patients with
      GD, and 30 eyes of 15 healthy subjects were included in this prospective study.
      The presence of TAO was evaluated clinically. The palpebral fissure height,
      degree of proptosis, ocular surface disease index (OSDI), Schirmer tear test,
      tear break-up time (TBUT), and conjunctival impression cytology were assessed.
      The results were first compared between the patient and the control groups.
      Results were then compared between the patients with TAO (group I) and without
      TAO (group II). RESULTS: The mean OSDI score in the patient group was 44.79 +/-
      11.83 and it was 21.17 +/- 9.89 in the control group (p  =  0.001). The mean
      Schirmer tear test score was 14.4 +/- 8.32 mm and 24.9 +/- 3.57 mm in the patient
      and control group, respectively (p  =  0.001). The mean TBUT in the patient group
      was 7.1 sec. In the control group it was significantly increased to 10 sec (p  = 
      0.003). The mean proptosis and interpalpebral distance did not show any
      difference between the GD patients and controls (p > 0.05). The patients with GD
      showed significant ocular surface damage in which 75.71% had grade 2-3 squamous
      metaplasia in temporal interpalpebral conjunctiva. Twenty-four (57%) eyes
      composed group I. There were no differences in the mean OSDI score, Schirmer tear
      test score, TBUT, and the amount of ocular surface damage between group I and
      group II (p > 0.05). CONCLUSIONS: Dry eye findings and the ocular surface damage
      in GD were most likely associated with the ocular surface inflammation. Before
      the development of the classic findings of TAO, ocular surface inflammation can
      be the only presenting clinical sign in GD.

PMID- 21174593
TI  - Diverse virulence of Staphylococcus aureus strains for the conjunctiva.
AB  - PURPOSE: To determine the virulence of Staphylococcus aureus strains in the
      rabbit conjunctiva. METHODS: Three strains of methicillin-sensitive S. aureus
      (8325-4, Newman, and UMCR1) and two strains of methicillin-resistant S. aureus
      (70490 and MW2) were analyzed. Rabbit bulbar conjunctivas (n >= 6 per group) were
      injected with 10(5) colony forming units (CFU) in 10 ul. Eyes were photographed
      and analyzed for pathology at 20 hr postinfection (PI) using slit lamp
      examination (SLE) to measure five parameters on a scale from 0 (normal) to 4
      (severe): injection, chemosis, iritis, corneal edema, and pinpoint conjunctival
      hemorrhages. The parameter grades were added to produce a SLE score. Bacteria
      were enumerated and histopathological analysis was done at 20 hr PI.
      Myeloperoxidase assays were performed on conjunctival swabs (n >= 3 per strain)
      at 0 and 20 hr PI. RESULTS: Conjunctivas injected with 8325-4 or Newman had SLE
      scores of 1.67 +/- 0.12 and 0.81 +/- 0.16, respectively. Strain 70490 produced an
      average SLE score of 2.94 +/- 0.47, whereas MW2 produced a score of 5.04 +/-
      0.73. UMCR1 produced severe conjunctivitis having a SLE score of 13.25 +/- 0.80.
      Only strain UMCR1 grew in the conjunctiva showing a 2.7 log increase in CFU; all
      other strains remained near the inoculated numbers or decreased as much as 1.85
      logs. Myeloperoxidase activity was greatest in the tear film of UMCR1 infected
      eyes with over one million PMN present at 20 hr PI. CONCLUSIONS: Only one S.
      aureus strain, UMCR1, was able to cause a reproducible severe conjunctivitis.
      This conjunctival infection could be used to test new antimicrobials and to help
      understand the pathogenesis of conjunctivitis, especially in terms of overcoming
      the host defenses.

PMID- 21174594
TI  - Arabinogalactan as active compound in the management of corneal wounds: in vitro
      toxicity and in vivo investigations on rabbits.
AB  - PURPOSE: Aims of the present investigation were to prove that natural
      polysaccharide arabinogalactan (AG) is well tolerated after ocular administration
      and exerts a high restoring effect on corneal epithelium abrasions. MATERIALS AND
      METHODS: AG interactions with corneal cells, as well as its effect on their
      proliferation, were evaluated employing rabbit corneal epithelial cell cultures.
      The effects due to the presence of benzalkonium chloride (BAK) were also studied
      on cell cultures, ex vivo on rabbit isolated corneas, evaluating the hydration
      level, and on the healing rate of experimental corneal wounds in rabbits.
      Furthermore, the healing process of corneal lesions treated with an experimental
      5.0% AG solution was studied and compared with those obtained applying solutions
      of hyaluronic acid and tamarind seed polysaccharide, both chosen as a reference
      by virtue of their well-known adjuvant properties on corneal trophism; the study
      was carried out by light and transmission electron microscopy. RESULTS: BAK
      showed toxic effects on corneal epithelium in all experiments. AG proved to
      stimulate the growth of the corneal epithelial cells by interacting at the level
      of the cell plasma membrane. The microscopy observations of the epithelial
      surface of AG-treated damaged corneas revealed a well-restored and histologically
      organized ultrastructure characterized by fully formed microvilli and glycocalyx;
      the healing process resulted faster with respect to spontaneously recovered
      untreated corneas. CONCLUSION: Our results suggest that AG can interact with
      corneal epithelial cells without any toxic side effect; moreover, it proved to
      stimulate cell proliferation, thus promoting tissue re-epithelialization and
      reorganization just 48 hr post-wounding.

PMID- 21174595
TI  - The effects of nicergoline on corneal nerve regeneration in rat corneas after
      photorefractive keratectomy.
AB  - PURPOSE: We wanted to investigate the effect of nicergoline on corneal nerve
      regeneration in rat corneas after photorefractive keratectomy (PRK). METHODS:
      Twenty Sprague-Dawley male rats were divided into two groups, the control group
      and the group that had been treated with nicergoline for 4 weeks. Corneal wound
      healing was evaluated by fluorescein staining after PRK. Immunofluorescent
      staining was performed in the rat corneas at 1 month after PRK with monoclonal
      antibodies for class III beta-tubulin, calcitonin gene-related peptide (CGRP),
      and substance P (SP). The stained nerve areas were calculated using an image
      analysis program. RESULTS: The corneal wound healing rate was not significantly
      different between the nicergoline-treated rats and the control rats after PRK. At
      1 month after PRK, the tubulin-positive, substance P-positive, and CGRP-positive
      nerve areas were significantly greater in the treatment group than those in the
      control group. CONCLUSION: Nicergoline treatment increased the corneal nerve area
      in the rats after they had undergone PRK. Nicergoline may help patients who have
      a decreased corneal sense, such as those with neurotrophic keratopathy and those
      patients after they undergo refractive surgery.

PMID- 21174596
TI  - Effect of SPP 301, an endothelin antagonist, on intraocular pressure in
      glaucomatous monkey eyes.
AB  - PURPOSE: To evaluate the effect of topical application of avosentan (SPP 301),
      endothelin receptor type A antagonist, on intraocular pressure (IOP) in monkey
      eyes with laser-induced unilateral glaucoma. MATERIALS AND METHODS: A multiple
      dose study was performed in eight glaucomatous monkey eyes that were topically
      treated with SPP 301 by applying a 50 ul drop (25 ul * 2) at 9:30 a.m. and 3:30
      p.m. for 5 consecutive days at three concentrations (0.003%, 0.03%, or 0.3%). IOP
      was measured hourly for 6 hrs on each day of the study beginning at 9:30 a.m. for
      one baseline day, one vehicle-treated day, and treatment days 1, 3, and 5.
      RESULTS: Twice daily administration of each of the three concentrations of SPP
      301 for 5 days significantly (p < 0.05) reduced IOP. The maximum reduction in IOP
      occurred 2 or 3 hrs after morning dosing and was 1.8 +/- 0.8 (mean +/- SEM) mmHg
      (6%) for 0.003% SPP 301, 4.1 +/- 0.7 mmHg (13%) for 0.03% SPP 301, and 7.1 +/-
      1.3 mmHg (21%) for 0.3% SPP 301. The longest duration of IOP reduction was for 2
      hrs with 0.003% SPP 301, and was for at least 6 hrs with 0.03% and 0.3%
      concentrations. Compared to 0.03% or 0.003% concentrations, 0.3% SPP 301 produced
      a greater (p < 0.05) IOP reduction. IOP was reduced in fellow untreated normal
      eyes 2 hr after morning dosing with 0.3% SPP 301, maximum reduction in IOP (11%)
      occurred on day 1. Of the eyes treated with 0.3% SPP 301, one eye demonstrated
      mild conjunctival discharge and one eye was closed for 5 min after dosing.
      CONCLUSION: Topically applied SPP 301, an endothelin antagonist, reduced IOP in
      glaucomatous monkey eyes in a dose-dependent manner. Endothelin antagonists, a
      novel class of compound, may have potential for the treatment of glaucoma.

PMID- 21174597
TI  - Ocular changes associated with topiramate.
AB  - PURPOSE: To determine the changes in refractive error, and the cornea, anterior
      chamber, and retina induced by topiramate. METHODS: The study included 76 eyes of
      38 patients that began to use topiramate due to migraine. Following
      ophthalmological examination, all of the patients underwent central corneal
      thickness (CCT), anterior chamber volume (ACV), anterior chamber depth (ACD), and
      anterior chamber angle (ACA) measurement using a Scheimpflug camera, as well as
      macular thickness, retinal and retinal nerve fiber layer thickness (RNFLT)
      measurements using optical coherence tomography (OCT). These procedures were
      repeated 15, 30, and 90 days after the initiation of topiramate therapy. RESULTS:
      The median refractive error value showed a statistically significant increase
      from -0.25 diopters (D) to -0.62 D at the 90th day follow-up (P < 0.001). Mean
      CCT was 570.56 um before treatment and increased to 573.69 um at the 15th day
      follow-up, 575.31 um at the 30th day follow-up, and 574.56 um at the 90th day
      follow-up; however, these changes were not statistically significant. Mean ACV,
      ACD, and ACA did not exhibit statistically significant changes. Mean retinal
      thickness (RT) increased during the treatment from 263.46 um to 271.60 um, which
      was not statistically significant. The initial mean RNFLT was 100.56 +/- 15.36 um
      and significantly increased to 110.2 +/- 8.41 um and 111.03 +/- 14.59 um at the
      30th and 90th day follow-ups, respectively (P  =  0.01 and P  =  0.004,
      respectively). CONCLUSIONS: During the 3-month follow-up of patients using
      topiramate 50 mg d(-1) significant myopic shift and an increase in RNFLT were
      observed. Further studies are warranted in order to assess the effects of
      topiramate when used long term and at higher doses.

PMID- 21174598
TI  - Dynamic association between intraocular pressure and spontaneous pulsations of
      retinal veins.
AB  - PURPOSE: The amplitude of spontaneous retinal venous pulsations (SRVP) is known
      to be affected by intraocular pressure (IOP), retinal venous pressure, and
      intracranial pressure (ICP). This study characterized SRVPs adjacent to the disc
      and quantified changes in the amplitude of these pulsations during IOP
      manipulation in normal subjects. METHODS: The study included 12 subjects (40 +/-
      15, 4 females, 8 males). Baseline IOP (range 10-25 mmHg) was measured and SRVP
      recorded using the dynamic retinal vessel analyzer (DVA). IOP was lowered using
      aproclonidine 0.5% and measured every 15 min, followed by dynamic recording of
      SRVP. Two subjects were also tested with timolol 0.5%, and three were treated
      with a placebo drop. Mean amplitude of SRVP was determined within each sample at
      the same site. Blood pressure and heart rate were tracked continuously. RESULTS:
      Amplitude of SRVP decreased in all subjects with reduction of IOP with
      aproclonidine and timolol. Mean SRVP amplitude was 8.5 +/- 6 MUm at baseline and
      reduced to 2.5 +/- 1.8 MUm after 45 min (p < 0.0001). IOP fell from 14.4 +/- 2.6
      mmHg to 10.2 +/- 2.9 mmHg over the same period (p < 0.001). Venous diameter,
      blood pressure, and heart rate did not change significantly from the baseline.
      Analysis of waveforms showed a slight phase shift only (150 +/- 78.5 ms, p =
      0.93) between disc veins and adjacent retinal vein. CONCLUSION: SRVPs in the
      peripapillary retina have similar waveform characteristics to those at the disc.
      SRVP amplitudes are reduced by manipulation of IOP downwards with pharmacological
      intervention. The relationship was consistent in all individuals tested for two
      classes of drugs and was independent of BP or heart rate changes.

PMID- 21174599
TI  - Pigment epithelium-derived factor gene polymorphisms in exudative age-related
      degeneration in a chinese cohort.
AB  - PURPOSE: To investigate polymorphisms in the pigment epithelium-derived factor
      (PEDF) gene in a Chinese cohort with exudative age-related macular degeneration
      (AMD). METHODS: Two common single nucleotide polymorphisms (SNPs), Met72Thr
      (rs1136287) and -5736T>C (rs12150053), were genotyped, and four tagSNPs (tSNPs)
      were detected statistically in the PEDF gene of 168 exudative AMD patients and
      230 age- and sex-matched control participants. Genetic analyses for additive,
      dominant, and recessive models were performed on all the available genotype data.
      All the possible haplotypes of these six SNPs were detected. RESULTS: No
      association was found between the patients and the control participants in the
      allele frequencies for any individual SNP. There was evidence to suggest that
      heterozygotes for rs1136287 (C/T) exerted a protective effect against exudative
      AMD (additive model, OR 0.59, CI 0.36-0.95, p = 0.03), but none of the p-values
      in the other genotype groups were statistically significant. Likewise, haplotype
      analyses did not provide any evidence for an association between SNPs in the PEDF
      gene and the risk of exudative AMD in this Chinese cohort (p > 0.05).
      CONCLUSIONS: Detection of SNPs in the PEDF gene was not found to be significantly
      associated with exudative AMD in the Chinese cohort. Further studies of
      comprehensive PEDF gene variations are required to characterize the
      susceptibility of PEDF gene in the pathogenesis of AMD.

PMID- 21174600
TI  - Cullin5 reduces retinal cell death induced by glutamate toxicity.
AB  - PURPOSE: To investigate the expression in the mouse retina and the function in a
      retinal cell of cullin5 that is known as a protein that is associated with
      ubiquitilation. METHODS: The retinal sites of expressing cullin5 were determined
      by immunohistochemistry with a specific antibody for cullin5. Retinal cells were
      transfected with HA-tagged cullin5 using an adenovirus system, and retinal cells
      were exposed to L-glutamate with or without an over-expression of cullin5.
      RESULTS: Cullin5 was expressed in the retina of C57BL/6N mice and the retinal
      ganglion cell layer (RGL) of retina was strongly immunostained. Further, cullin5
      was localized in the retinal ganglion cell (RGC). An over-expression of cullin5
      reduced the percentage of retinal cell deaths induced by L-glutamate.
      CONCLUSIONS: The expression of cullin5 on retinal cells and reduction in the
      percentage of dead retinal cells induced by L-glutamate suggest that cullin5 has
      neuroprotective properties in retinal cells.

PMID- 21174601
TI  - Camptothecin induces apoptosis of human retinoblastoma cells via activation of
      FOXO1.
AB  - PURPOSE: The purpose of this study was to investigate the pro-apoptotic effect of
      camptothecin (CPT) on Y79 retinoblastoma cells and the role of Forkhead box,
      class O (FOXO1) in CPT-induced apoptosis. METHODS: CPT-induced apoptosis was
      determined by flow cytometry with annexin V-FITC positive cells and Western blot
      of PARP expression, respectively. The expressions of FOXO1 were detected by
      Western blot. The transcriptional activity of FOXO1 was determined by luciferase
      reporter assay. siRNAs specifically inhibiting FOXO1 were used, and flow
      cytometry and Western blot were executed to test the role of FOXO1 in CPT-induced
      apoptosis. RESULTS: CPT was extremely effective in inducing apoptosis of Y79
      retinoblastoma cells. FOXO1 was highly expressed in Y79 cells. CPT not only
      elevated the FOXO1 dephosphorylation level but also promoted its transcriptional
      activity, suggesting that the activation of FOXO1 was, at least in part,
      triggered by CPT. The decreased annexin V positive cells and less PARP cleavage
      demonstrated that siRNAs-mediated inhibition of FOXO1 significantly abrogated CPT
      induced apoptosis, indicating that FOXO1 plays an important role in CPT-induced
      apoptosis. Moreover, the expression of Bim was also elevated with the treatment
      of CPT, which is in accordance with the activation of FOXO1. CONCLUSIONS: Our
      study provides the evidence that a high level of endogenous FOXO1 expression in
      retinoblastoma cells contributes, at least in part, to CPT-induced apoptosis,
      which may help broad application of CPT in retinoblastoma therapy in the future.

PMID- 21174602
TI  - An examination of presenteeism measures: the association of three scoring methods
      with health, work life, and consumer activation.
AB  - The objective of this study was to assess the validity of 3 scoring techniques
      for presenteeism measures by exploring their relationship with patient
      activation, health, job satisfaction, and socioeconomic characteristics. The
      sample consisted of 631 employees from 2 predominantly white-collar employee
      groups in the northern Midwest. Employees completed the World Health
      Organization's Health and Work Performance Questionnaire, a wellness profile, and
      the Patient Activation Measure. Absolute measures reflect self-rated performance,
      while relative and stratified measures compare self-rated performance to that of
      co-workers. Multivariate analyses were used to validate scoring measures. All
      measures of presenteeism were positively correlated with being nonwhite, income,
      and smoking. The significance of age, employment, mental health, and patient
      activation depends on how presenteeism is defined. Practitioners must carefully
      consider which scoring method best addresses their program goals and objectives.
      Clearer measurement guidelines are needed.

PMID- 21174604
TI  - Have inadequate delivery systems hampered the clinical success of inhaled
      disodium cromoglycate? Time for reconsideration.
AB  - IMPORTANCE OF THE FIELD: Disodium cromoglycate (DSCG) fits with the perception of
      a safe drug, but conclusions from questionable meta-analyses reduced its use. In
      addition, drug delivery aspects, such as hygroscopicity and the poor performance
      of delivery systems, were not considered to be important determinants of
      therapeutic failures. AREAS COVERED IN THIS REVIEW: Drug delivery aspects and
      parameters affecting lung deposition and distribution, important parameters for
      therapeutic efficacy, are addressed. In addition, the distribution and ratio of
      mast cell tryptase and chymase-positive phenotypes in the lungs and their role in
      the prostaglandin and leukotriene pathway are discussed. WHAT THE READER WILL
      GAIN: Information on why in vitro data are an excellent tool to understand better
      therapeutic failures associated with the moisture sensitivity of DSCG and the
      difficulty in handling and operating DSCG delivery systems in a therapeutically
      reliable way. TAKE HOME MESSAGE: Pharmacological efficacy of DSCG has been
      demonstrated in animals and humans. If the drug is delivered to the site of
      inflammation in an effective dose, a reliable therapeutic effect can be expected.
      DSCG has extra properties and potential unspecific antiviral properties and may
      offer new therapeutic treatment aspects for asthma and viral-induced
      bronchiolitis in early childhood.

PMID- 21174605
TI  - In vitro and in vivo testing methods for respiratory drug delivery.
AB  - IMPORTANCE OF THE FIELD: Successful respiratory drug delivery for local and
      systemic purposes is predicated on the availability of in vitro and in vivo
      methods for determining drug delivery and disposition following respiratory
      administration. AREAS COVERED IN THIS REVIEW: In this review, the relevance of
      new in vitro and in vivo methods for screening respiratory drug delivery is
      discussed. Specific topics covered include in vitro particle size
      characterization, in vitro dissolution test methods for respiratory formulations
      and in vitro respiratory absorption and disposition screening methods.
      Furthermore, in vivo respiratory dosing methods, in vivo respiratory aerosol
      deposition and drug absorption screening methods, and correlation between in
      vitro and in vivo methods are reviewed. WHAT THE READER WILL GAIN: After reading
      this article, the reader will have an enriched knowledge regarding the various in
      vitro and in vivo testing methods for respiratory drug delivery. Most
      importantly, this paper will make it possible for readers to appreciate the
      strengths and weaknesses of each test method, which in turn will assist them in
      selecting specific methods that suit their scientific needs. TAKE HOME MESSAGE:
      New in vitro and in vivo methods for screening respiratory drug delivery are
      indispensible, especially from the respiratory drug development and quality
      control perspective. Each method has unique advantages and disadvantages that
      influence method selection and data interpretation. Although in vitro methods are
      used during drug development, they augment rather than substitute in vivo
      methods.

PMID- 21174607
TI  - Transplantable delivery systems for in situ controlled release of bisphosphonate
      in orthopedic therapy.
AB  - IMPORTANCE OF THE FIELD: Bisphosphonates (BPs), structurally similar to
      pyrophosphates and functionally superior in restraining osteoclast-induced bone
      resorption, have been widely used as clinical drugs in the treatment of
      osteoporosis, bone voids and associated inflammation. However, owing to their
      high aqueous solubility and the consequently high rate of loss during oral
      administration, the loading and targeting of BPs pose major challenges in
      practice. Alternative delivery routes such as nasal, subcutaneous/intramuscular
      injection have contributed little to improving the bioavailiability and efficacy
      of BPs. To improve and optimize the delivery efficiency and efficacy of BPs,
      numerous strategies have been developed and adopted. Studies on controlled
      release of BPs provide important information on the fabrication of BP delivery
      systems for in situ treatment. As BPs play an important therapeutic role in
      osteoporosis and similar diseases, it has become essential and vital to survey
      various reported fabrication methodologies of these systems and the consequential
      orthopedic treatments so as to keep abreast with advances in their clinical use.
      AREAS COVERED IN THIS REVIEW: Transplantable delivery systems for controlled
      release of BP are reviewed from literature published since 2000. The fabrication
      pathways and the release of BPs from various material systems are discussed in
      case studies. Recent progress in CaP models based on the strong and specific
      chelation between BPs and calcium phosphate crystals is highlighted. WHAT THE
      READER WILL GAIN: This review offers an outline of the advances in BP controlled
      release and delivery systems for orthopedic therapy. TAKE HOME MESSAGE:
      Understanding the cutting-edge BP controlled release and delivery systems for in
      situ treatment is key to the successful design of a more promising and perfect
      delivery system for orthopedic therapy. Moreover, developing such delivery
      systems incorporating the numerous advantages of BPs and controlled release
      environment requires substantially more flexible models to control better the
      fate of BP drugs.

PMID- 21174606
TI  - Ocular drug delivery - a look towards nanobioadhesives.
AB  - IMPORTANCE OF THE FIELD: A major challenge emanating in the design of topical
      ophthalmic preparations is their short precorneal residence time. Retention of a
      drug delivery system in the front of the eye is thus desirable. One solution
      identified to address this concern is a retentive system that can preferably be
      delivered in a liquid drop form and ultimately remain attached to the corneal
      tissue owing to incorporation of a bioadhesive component. Forward-thinking
      approaches are required to achieve advancements in this approach for the
      attainment of an effective drug concentration at the site of action. Accordingly,
      several investigators have identified the benefits of nanotechnology-based drug
      delivery systems for ophthalmic drug delivery. AREAS COVERED IN THIS REVIEW: A
      concerted effort was made to review critically all 'nanobioadhesives', that is,
      nanosystems designed for ocular drug delivery with the goal of attaining
      prolonged ocular retention, in a systematic, chronological manner, from their
      reported point of inception to the present. WHAT THE READER WILL GAIN: A
      perspective on possible future trends in this growing field of ocular drug
      delivery is formulated. TAKE HOME MESSAGE: The importance of and need for new
      developments in the field of ocular nanobioadhesives is emphasized.

PMID- 21174608
TI  - A new volume of Acta Oncologica.

PMID- 21174609
TI  - Feasibility of safe ultra-high (EQD(2)>100 Gy) dose escalation on dominant intra
      prostatic lesions (DILs) by Helical Tomotheraphy.
AB  - PURPOSE: to verify the possibility of using Helical Tomotherapy to safely
      escalate dose to single or multiple highly radioresistant dominant intra
      prostatic lesions (DILs) as assessed by functional magnetic resonance imaging
      (MRI). MATERIAL: in seven intermediate/high risk patients, T2WI, T1WI and DWI MRI
      imaging showed evidence of one DIL in four patients and two DILs in three
      patients in the peripheral zone of the prostate. The planning strategy was to
      deliver median doses of 80, 90, 100 and 120 Gy to PTVDIL while delivering 71.4
      Gy/28 fractions (EQD(2)=75 Gy) to the remaining portion of PTV. A higher priority
      was assigned to rectal constraints relative to DIL coverage. Rectal NTCP
      calculations were performed using the most recently available model data.
      RESULTS: the median dose to DIL could safely be escalated to at least 100 Gy
      (EQD(2,alpha/beta=10)=113 Gy) without violating safe constraints for the organs
      at risk. Typical rectal NTCP values were around or below 1-3% for G3 toxicity and
      5-7% for G2-G3 toxicity. For the 100 Gy DIL dose boost strategy, mean D95% of DIL
      and PTVDIL were 98.8 Gy and 86.7 Gy, respectively. The constraints for bladder,
      urethra and femoral heads were always respected. CONCLUSIONS: IGRT by Helical
      Tomotherapy may permit the safe escalation of EQD(2,alpha/beta=10) to at least
      113 Gy to DILs without significantly increasing rectal NTCP compared to plans
      without dose escalation. A Phase I-II clinical study is warranted.

PMID- 21174611
TI  - Critical discussion of social-cognitive factors in smoking initiation among
      adolescents.
AB  - Social-cognitive models have often been used in research on prevention in
      adolescent populations, even though the models were designed to describe adult
      behavior. The aim of the study reported here was to examine critically and
      constructively the five social-cognitive factors in the 'attitude, social
      influence, self-efficacy' (ASE) model. Methods. The examination draws on the
      results of a qualitative follow-up study of smoking initiation based on semi
      structured interviews and observations of 12 adolescents in two Danish school
      classes, grades 7 and 8. The qualitative study was conducted in connection with
      and sampled from a large quantitative study and the results of both studies are
      discussed. In the analyses, we explored the ASE constructs according to how they
      are described in the ASE theory. Furthermore, we examined contradictions and
      aspects which are not explained in the model and if relevant discussed these
      aspects using other theoretical frameworks. Results. The results showed that
      aspects other than those in the ASE model are also important. Smoking initiation
      was often situational and unplanned and was sometimes used in negotiating social
      relationships and identity. Furthermore, the social-cognitive models are based on
      the assumption that adolescents talk about smoking norms and have a high degree
      of individual reflexivity, which is not always characteristic of adolescent
      behavior. Conclusion. Applying theoretical models in health research should be a
      continuous process of both applying the model and discussing the theoretical
      assumptions of the model when applied to a specific sample. The results of the
      qualitative study provide some support for use of the ASE model, but the results
      also suggest that further studies are needed to explore how social-cognitive
      models can be expanded to be more comprehensive behavioral models.

PMID- 21174610
TI  - A randomised feasibility/phase II study (SBG 2004-1) with dose-dense/tailored
      epirubicin, cyclophoshamide (EC) followed by docetaxel (T) or fixed dosed dose
      dense EC/T versus T, doxorubicin and C (TAC) in node-positive breast cancer.
AB  - The aim of the study was to evaluate the feasibility of tailored and dose-dense
      epirubicin and cyclophosphamide followed by docetaxel as adjuvant breast cancer
      therapy. Material and methods. Patients with node-positive breast cancer received
      either four cycles of biweekly and tailored EC (epirubicin 38-60-75-90-105-120
      mg/m(2), cyclophosphamide 450-600-900-1200 mg/m(2)) followed by four cycles of
      docetaxel (60-75-85-100 mg/m(2)) (arm A) or the same regimen with fixed doses
      (E(90)C(600) + 4 -> T(75) + 4) (arm B) or docetaxel, doxorubicin and
      cyclophosphamide (T(75)A(50)C(500)) every three weeks for six cycles (arm C). All
      patients received G-CSF support and prophylactic ciprofloxacin. Results. One
      hundred and twenty-four patients were randomised in the study. In the A, B and C
      arm, 17% 19% and 3% of the patients had one or more cycles delayed due to side
      effects whereas 24%, 5% and 15% experienced a grade 3 infection or febrile
      neutropenia. After the introduction of an extra week between the EC and T parts
      in the A and B arms, grade 3 hand-foot-skin reactions were reduced from 5 to
      0.2%. Twenty-nine percent (A and B) and 20% (C) of the patients were hospitalised
      due to side-effects. Discussion. Dose-dense and tailored EC/T can be given with
      manageable toxicity and is after adjustment presently studied in the phase III
      Panther trial.

PMID- 21174612
TI  - A phase I study of recombinant human interleukin-21 (rIL-21) in combination with
      sunitinib in patients with metastatic renal cell carcinoma (RCC).
AB  - BACKGROUND: sunitinib induces partial responses in 47% of patients with
      metastatic renal cell carcinoma (mRCC). However, the achievement of complete
      responses remains scarce and all patients will eventually develop progressive
      disease. Recombinant interleukin-21 (rIL-21) is a novel cytokine, which is
      believed to deliver sustained cellular anti-tumor response and the combination of
      both agents may work synergistically. MATERIAL AND METHOD: from July 2007 to July
      2008 in this phase I trial nine therapy-naive patients with metastatic RCC in
      five European centers were enrolled. Patients with either good or intermediate
      risk according to Memorial Sloan-Kettering Cancer Center (MSKCC) were eligible
      without restrictions to histology subtype nor measurable disease. Patients were
      treated with increasing doses of rIL-21 administered subcutaneously (s.c.) in
      combination with sunitinib 50 mg once daily (OD) orally at the '4 weeks on/2
      weeks off' schedule. Dose-escalation was applied by a conventional '3+3 design'.
      Planned dose levels (DL) for rIL-21 were 3, 10, 30 and 100 microg/kg s.c. The
      primary endpoint was to determine the maximum tolerated dose (MTD) and
      recommended dose (rd). secondary objectives included pharmacokinetics of
      sunitinib and ril-21, and the induction of ril-21 antibodies. RESULTS: at 10
      microg/kg two dose-limiting toxicities (DLT) occurred in four patients,
      consisting of grade 4 neutropenia and grade 3 thrombocytopenia. The MTD was 3
      microg/kg rIL-21 combined with sunitinib 50 mg OD at the '4 weeks on/2 weeks off'
      schedule. Frequent occurring adverse events were injection site reaction,
      stomatitis, fatigue and dysgeusia. CONCLUSIONS: the combination of sunitinib 50
      mg at the '4 weeks on/2 weeks off' schedule and 10 microg/kg IL-21 was not
      tolerated due to hematological DLTs. The dose level of 3 microg/kg rIL-21 was
      considered too low to be therapeutically relevant for further evaluation and
      therefore the study was discontinued.

PMID- 21174613
TI  - Capecitabine and hand-foot syndrome.
AB  - Hand-foot syndrome (HFS), or palmar-plantar erythrodysesthesia, is a common side
      effect in patients taking long-term 5-fluorouracil treatment and is the most
      frequently reported side effect of oral capecitabine therapy (>= 50% of
      patients). Although the pathogenesis of HFS is not fully understood, it may be
      due to damaged deep capillaries in the soles of the feet and palms of the hands,
      leading to a COX inflammatory-type reaction, or related to enzymes involved in
      the metabolism of capecitabine, namely, thymidine phosphorylase and
      dihydropyrimidine dehydrogenase. Ethnic variations in the clinical manifestation
      of HFS warrant further attention, and an alternative system for grading HFS in
      non-white patients has been proposed. In addition to treatment interruption and
      dose reduction, supportive treatments can help alleviate symptoms. Because
      capecitabine is an oral therapy administered at home, it is crucial that patients
      understand the importance of complying with treatment, be aware of the
      possibility of HFS, and inform the doctor or nurse immediately if symptoms of HFS
      develop. Several cases of HFS are presented.

PMID- 21174614
TI  - Alien hand syndrome: a case report and description to rehabilitation.
AB  - BACKGROUND: Alien hand syndrome (AHS) is a neurological disorder in which
      movements are performed against conscious will. It is rare but significant due to
      its disability impact on everyday life. This case highlights the clinical
      features, recovery course and response to rehabilitation of a patient with a
      dominant anterior cerebral artery territory infarct. METHODS: Single case report.
      RESULTS: Clinical signs and symptoms included right hemiparesis, hemianesthesia,
      dysphagia, language and cognitive dysfunction, personification and autonomous
      movement of the affected limb; involuntary grasping of objects interfered with
      his activities of daily living (ADL). Education for diagnosis and compensatory
      strategies of AHS, including visualisation, distraction of affected limb and
      maintaining a slow/steady pace with activities decreased the frequency of his AHS
      movements from 10 times to twice a day. Over the course of 4 months the
      rehabilitation treatment targeted toward the specific needs of the patient,
      allowed improvement in his ADL. Commonly used upper extremity motor recovery
      outcome measures like the Chedoke McMaster Stroke Assessment cannot be considered
      as a sensitive tool for AHS. More sensitive outcome measures are needed to be
      determined for this condition. CONCLUSION: This case distinguishes the clinical
      findings and description to rehabilitation in a case of AHS.

PMID- 21174615
TI  - Using video-capture virtual reality for children with acquired brain injury.
AB  - OBJECTIVE: To assess the use of a video-capture projected VR system for children
      with acquired brain injury (ABI), and to compare their performance to that of
      matched healthy controls. SUBJECTS: Thirty-three children (age range: 6-11.4
      years) were divided into two groups: 17 children with ABI and 16 controls matched
      for age, gender and maternal education. METHODS: Participants experienced three
      video-captured virtual environments and completed the SFQ child at the end of
      each specific environment. Participants with ABI experienced three virtual
      reality (VR) sessions over a period of 10 days. Attention was evaluated using the
      TEA-Ch. Upper extremity motor abilities were evaluated with the Melbourne
      Assessment, and self-care abilities were evaluated with the PEDI. RESULTS: The
      video-capture projected system differentiated between the performance of children
      with ABI and control participants. There was a correlation between VR performance
      and some attention factors and self-care abilities. No significant correlations
      were found between performance in the Melbourne assessment and performance within
      VR. CONCLUSIONS: The results highlight the potential of the video-capture virtual
      reality as a tool in the rehabilitation process of children with ABI.

PMID- 21174616
TI  - Influence of gene-gene interactions on response to albuterol therapy.

PMID- 21174617
TI  - Proteomic changes associated with breast cancer progression in the MCF10AT model.

PMID- 21174619
TI  - VKORC1, CYP2C9 and CYP4F2 genetic-based algorithm for warfarin dosing: an Italian
      retrospective study.
AB  - AIM: A total of 371 patients under stable warfarin therapy were retrospectively
      selected to develop a pharmacogenetic algorithm to identify the individual
      maintenance dose. MATERIALS & METHODS: The variables that were entered into the
      algorithm were: VKORC1, CYP2C9 and CYP4F2 polymorphisms, body surface area and
      age. RESULTS: The percentage of cases whose predicted mean weekly warfarin dose
      was within 20% of the actual maintenance dose was 51.8% considering patients
      overall, and were 36.2, 66.2 and 55.4%, respectively, taking into account
      patients requiring low (<=25 mg/week), intermediate (25-45 mg/week) and high
      (>=45 mg/week) doses. The algorithm could correctly assign 73.8 and 63.2% of
      patients to the low- and high-dose regimens, respectively. We developed and
      validated a pharmacogenetic algorithm in a series of Italian patients, we then
      tested, in the same series of italian patients, the formulas of three published
      algorithms. These three algorithms were developed and validated by their authors
      in a series of patients different from our own. The performance of our algorithm
      in our patients series was slightly higher than that achieved when using the
      three other algorithms in our patients series. CONCLUSION: The high predictive
      accuracy of low and high warfarin requirements of our algorithm warrants its
      application in prospective studies for clinical validation.

PMID- 21174621
TI  - The effect of ESR1 and ESR2 gene polymorphisms on the outcome of rheumatoid
      arthritis treatment with leflunomide.
AB  - AIM: Leflunomide is the drug used in the therapy for rheumatoid arthritis (RA).
      Previous studies indicated that the efficacy of the therapy with antirheumatic
      drugs is more effective in men than in women. Moreover, estrogens can decrease
      the anti-inflammatory action of leflunomide. Estrogens act through the estrogen
      receptors ESR1 and ESR2. In ESR1 and ESR2 genes, several polymorphisms have been
      detected. The aim of the present study was to examine the association between
      polymorphisms in the ESR1 and ESR2 genes and the response to treatment of RA
      patients with leflunomide. MATERIALS & METHODS: The study was carried out on 115
      women, mean age 54.1 +/- 11.0 years, diagnosed with RA and treated with
      leflunomide (20 mg daily). RESULTS: Our results indicated a better response to
      treatment in patients with ESR1 rs9340799 AA and rs2234693 TT genotypes after 12
      months of therapy. In these patients, the improvement of erythrocyte
      sedimentation rate, patient's global assessment of disease activity on a 100 mm
      visual analog scale and disease activity score values was greater than in
      patients with other genotypes. The ESR1 rs9340799-rs2234693 A-T haplotype was
      associated with a better response to treatment, the G-C haplotype with a worse
      response and the A-C haplotype was neutral. There were no statistically
      significant associations of response to treatment with ESR2 gene rs4986938 and
      rs1256049 polymorphisms. CONCLUSION: The results of the present study suggest
      that ESR1 gene polymorphisms in females with RA may be associated with the
      response to treatment with leflunomide.

PMID- 21174620
TI  - Gender-specific genomic profiling in metastatic colorectal cancer patients
      treated with 5-fluorouracil and oxaliplatin.
AB  - AIMS: Survival and response rates in metastatic colorectal cancer remain poor,
      despite advances in drug development. There is increasing evidence to suggest
      that gender-specific differences may contribute to poor clinical outcome. We
      tested the hypothesis that genomic profiling of metastatic colorectal cancer is
      dependent on gender. MATERIALS & METHODS: A total of 152 patients with metastatic
      colorectal cancer who were treated with oxaliplatin and continuous infusion 5
      fluorouracil were genotyped for 21 polymorphisms in 13 cancer-related genes by
      PCR. Classification and regression tree analysis tested for gender-related
      association of polymorphisms with overall survival, progression-free survival and
      tumor response. RESULTS: Classification and regression tree analysis of all
      polymorphisms, age and race resulted in gender-specific predictors of overall
      survival, progression-free survival and tumor response. Polymorphisms in the
      following genes were associated with gender-specific clinical outcome: estrogen
      receptor beta, EGF receptor, xeroderma pigmentosum group D, voltage-gated sodium
      channel and phospholipase A2. CONCLUSION: Genetic profiling to predict the
      clinical outcome of patients with metastatic colorectal cancer may depend on
      gender.

PMID- 21174622
TI  - Population-specific documentation of pharmacogenomic markers and their allelic
      frequencies in FINDbase.
AB  - AIMS: Population and ethnic group-specific allele frequencies of pharmacogenomic
      markers are poorly documented and not systematically collected in structured data
      repositories. We developed the Frequency of Inherited Disorders Pharmacogenomics
      database (FINDbase-PGx), a separate module of the FINDbase, aiming to
      systematically document pharmacogenomic allele frequencies in various populations
      and ethnic groups worldwide. MATERIALS & METHODS: We critically collected and
      curated 214 scientific articles reporting pharmacogenomic markers allele
      frequencies in various populations and ethnic groups worldwide. Subsequently, in
      order to host the curated data, support data visualization and data mining, we
      developed a website application, utilizing MicrosoftTM PivotViewer software.
      RESULTS: Curated allelic frequency data pertaining to 144 pharmacogenomic markers
      across 14 genes, representing approximately 87,000 individuals from 150
      populations worldwide, are currently included in FINDbase-PGx. A user-friendly
      query interface allows for easy data querying, based on numerous content
      criteria, such as population, ethnic group, geographical region, gene, drug and
      rare allele frequency. CONCLUSION: FINDbase-PGx is a comprehensive database,
      which, unlike other pharmacogenomic knowledgebases, fulfills the much needed
      requirement to systematically document pharmacogenomic allelic frequencies in
      various populations and ethnic groups worldwide.

PMID- 21174624
TI  - Pharmacogenetics of psoriasis.
AB  - Psoriasis is an inflammatory hyperproliferative skin disorder with a strong
      genetic predisposition. While many effective modalities are currently available
      for treating psoriasis, response to therapy is quite variable among patients. The
      genetic component underlying the response to pharmacotherapy in psoriasis is
      slowly beginning to emerge and represents a specialized field of genetics
      referred to as pharmacogenetics. The identification of genetic variants has the
      potential to improve the management of patient care by identifying which patients
      should avoid a specific drug and which patients should be administered a modified
      dose. A suitable approach in implementing such a strategy could potentially
      reduce medical costs and improve success of drug therapy. This article summarizes
      the clinical aspects of psoriasis, its genetic susceptibility and highlights the
      current landscape of genetic targets for psoriasis pharmacotherapy.

PMID- 21174625
TI  - Pharmacometabonomics as an effector for personalized medicine.
AB  - This article introduces and reviews the concept of pharmacometabonomics, with
      recent experimental exemplifications of the approach being described and
      discussed. Pharmacometabonomics seeks to predict the response of an individual to
      a stimulus (e.g., drug, toxin, surgery, nutrition and so on) prior to the
      stimulus or other perturbation. It is an integral part of top-down systems
      biology which aims to improve understanding of phenotypic differences and the
      impact of beneficial and pathological interventions. The pharmacometabonomic
      concept is also integral to the understanding of mammalian-gut microbiome
      cometabolic interactions and their consequences, including the impact on disease
      and therapy. Although the subject is only at an early stage and requires further
      exemplification and validation, the approach has major implications for improved
      efficiency in drug discovery efforts, for example, by enabling more careful
      selection of animals in preclinical studies, for better stratification of
      patients in drug clinical trials and for individualized therapies. It could also
      find application in population-wide large cohort studies and in studies of
      nutrition where it would allow the elucidation of health risk factors and provide
      easily measured surrogate biomarkers.

PMID- 21174623
TI  - How can we identify parasite genes that underlie antimalarial drug resistance?
AB  - This article outlines genome-scale approaches that can be used to identify
      mutations in malaria (Plasmodium) parasites that underlie drug resistance and
      contribute to treatment failure. These approaches include genetic mapping by
      linkage or genome-wide association studies, drug selection and characterization
      of resistant mutants, and the identification of genome regions under strong
      recent selection. While these genomic approaches can identify candidate
      resistance loci, genetic manipulation is needed to demonstrate causality. We
      therefore also describe the growing arsenal of available transfection approaches
      for direct incrimination of mutations suspected to play a role in resistance. Our
      intention is both to review past progress and highlight promising approaches for
      future investigations.

PMID- 21174626
TI  - Practical recommendations for pharmacogenomics-based prescription: 2010 ESF-UB
      Conference on Pharmacogenetics and Pharmacogenomics.
AB  - The present article summarizes the discussions of the 3rd European Science
      Foundation-University of Barcelona (ESF-UB) Conference in Biomedicine on
      Pharmacogenetics and Pharmacogenomics, which was held in June 2010 in Spain. It
      was focused on practical applications in routine medical practice. We provide
      practical recommendations for ten different clinical situations, that have either
      been approved or not approved by regulatory agencies. We propose some comments
      that might accompany the results of these tests, indicating the best drug and
      doses to be prescribed. The discussed examples include KRAS, cetuximab,
      panitumumab, EGFR-gefitinib, CYP2D6-tamoxifen, TPMT-azathioprine-6
      mercaptopurine, VKORC1/CYP2C9-warfarin, CYP2C19-clopidogrel, HLA-B*5701-abacavir,
      HLA-B*5701-flucloxacillin, SLCO1B1-statins and CYP3A5-tacrolimus. We hope that
      these practical recommendations will help physicians, biologists, scientists and
      other healthcare professionals to prescribe, perform and interpret these genetic
      tests.

PMID- 21174627
TI  - Comparison of warfarin pharmacogenetic dosing algorithms in a racially diverse
      large cohort.
AB  - AIMS: Multiple warfarin pharmacogenetic dosing algorithms have been reported to
      date. However, there is only limited information available on the performance of
      the algorithms that can be used with the results of a US FDA-cleared warfarin
      pharmacogenetic test. We compared the performance of warfarin pharmacogenetic
      dosing algorithms in a large racially diverse cohort. MATERIALS & METHODS:
      Warfarin pharmacogenetic dosing algorithms were identified using the PubMed
      database. Patient information from the International Warfarin Pharmacogenetics
      Consortium database was used to predict therapeutic warfarin doses according to
      each algorithm. By using bootstrapping analysis, the performance of algorithms
      was tested by comparing the mean absolute error and mean percentage of patients
      whose predicted dose fell within 20% of actual dose (percentage within 20%) in
      the entire cohort, and by race and therapeutic dose range. RESULTS: A total of 13
      algorithms and 1940 patients were included in the study. Overall, all the
      algorithms had similar performances (mean absolute error: 10.3 mg/week and mean
      percentage within 20%-41.4%). However, algorithms derived from racially mixed
      populations tended to perform better than those derived from single race
      populations. Mixed population algorithms had the lowest mean absolute error and
      the highest percentage within 20% across the racial groups. Most algorithms
      performed better in the intermediate-dose range (between 21 and 49 mg/week) than
      in the low (<=21 mg/week) or high-(>=49 mg/week) range. CONCLUSION: Published
      warfarin pharmacogenetic algorithms performed similarly, although mixed
      population algorithms tended to perform better than race-specific algorithms.

PMID- 21174629
TI  - Adult acquired major upper limb amputation in Norway: prevalence, demographic
      features and amputation specific features. A population-based survey.
AB  - PURPOSE: To estimate the prevalence of adult acquired major upper limb amputation
      in Norway. To describe this amputee population regarding demographic features and
      amputation specific features. To compare our data to data collected
      internationally. METHOD: Population-based cross-sectional study on adult upper
      limb amputees with acquired limb loss through or proximal to the radio-carpal
      joint. Patients were found in the databases of the two companies in Norway that
      make upper limb prostheses and in the medical records of three of the largest
      Norwegian hospitals. Data were collected by postal questionnaires. RESULTS: We
      estimated a population prevalence of 11.6 per 100,000 adults (n = 416). Our
      survey was not 100% comprehensive and the estimate is conservative. The amputees
      were predominantly men with traumatic, unilateral, distal amputations at a young
      age. There were significant gender- and amputation level differences in cause.
      Most amputees had used prostheses. About four in ten were in paid employment.
      CONCLUSIONS: Our findings are mainly consistent with earlier studies from other
      countries. Implications of our findings related to the planning of future health
      care for these patients are outlined, including suggestion of regional
      multidisciplinary rehabilitation emphasising occupational rehabilitation and
      focus on preventive measures. Potential areas of follow-up are suggested.

PMID- 21174630
TI  - Quality of life in patients with multiple sclerosis in Eastern Slovakia.
AB  - PURPOSE: Quality of life (QoL) is an important measure of the burden of disease
      and could be useful in evaluating patient management and practical interventions.
      The aim of this study was to explore the association of psychological and
      clinical variables with QoL in patients with multiple sclerosis (MS). METHODS:
      One hundred and fourteen consecutive patients (mean age 36.1 +/- 10.3 years, 72%
      female) from one MS centre completed the Hospital Anxiety and Depression Scale,
      the Fatigue Severity Scale and the Short-Form-36 Health Survey (SF-36).
      Functional disability was assessed using the Expanded Disability Status Scale.
      Multiple linear regression analyses were performed to analyse demographic,
      psychological and clinical data. RESULTS: Functional disability, depression and
      fatigue were found to be related inversely to the physical health subscale.
      Disease course, anxiety and depression were associated negatively with the mental
      health subscale. CONCLUSIONS: Functional disability, depression and fatigue were
      the main variables related to the perceived physical health subscale, and disease
      course, anxiety and depression to the perceived mental health subscale in the
      group of patients with MS. Thus, effective treatment of fatigue, anxiety and
      depression could be assumed to increase a patient's QoL.

PMID- 21174631
TI  - High prevalence of HIV type 1 subtype B' among heterosexuals in Western Hubei,
      Central China: bridging the epidemic into the general population.
AB  - A molecular epidemiological investigation (n = 62) conducted in western Hubei,
      Central China, revealed that HIV-1 subtype B' (Thailand variant of subtype B)
      predominated not only among former plasma donors (FPDs) (29/29, 100%) but also
      among heterosexuals (27/31, 87%), suggesting that subtype B' appears to bridge
      the spread from FPDs in the general population in this particular area in Central
      China.

PMID- 21174632
TI  - Active citizenship and acquired neurological communication difficulty.
AB  - PURPOSE: People with communication impairments may face barriers to civic
      participation, with resulting marginalisation of individuals who wish to be
      actively involved. The investigation aimed to explore the experience of civically
      engaged adults with acquired neurological communication difficulties. METHOD: Six
      people with acquired neurological communication difficulties were interviewed.
      Discussion included the definition of active citizenship, their civic
      involvement, motivations, related barriers and facilitators. Qualitative analysis
      was undertaken, with data categorised, coded and examined for recurring themes.
      RESULTS: All participants were active in disability-related organisations and
      four undertook wider civic roles. Motivations included activity being out with
      the home and wanting to effect change for themselves and the populations they
      represented. Disability group meetings were more positive experiences than
      broader community activities, which were associated with fatigue and frustration,
      commonly resulting from communication difficulties and unmet support needs. All
      participants identified a need for professional and public educational about
      disability and communication and made recommendations on content, methods and
      priority groups. CONCLUSIONS: For these participants civic engagement had
      positive and negative dimensions. Speech and language therapists should promote
      reduction of the barriers that impede the active citizenship rights of people
      with communication support needs. Civic participation may be a relevant measure
      of outcome in communication impaired populations.

PMID- 21174634
TI  - Training conditions influence walking kinematics and self-selected walking speed
      in patients with neurological impairments.
AB  - Gait training is a major focus of rehabilitation for many people with
      neurological disorders, yet systematic reviews have failed to identify the most
      effective form of gait training. The main objective of this study was to compare
      conditions for gait training for people with acquired brain injury (ABI).
      Seventeen people who had sustained an ABI and were unable to walk without
      assistance were recruited as a sample. Each participant was exposed to seven
      alternative gait training conditions in a randomized order. These were: (1)
      therapist manual facilitation; (2) the use of a gait-assistive device; (3)
      unsupported treadmill walking; and (4) four variations of body weight support
      treadmill training (BWSTT). Quantitative gait analysis was performed and Gait
      Profile Scores (GPS) were generated for each participant to determine which
      condition most closely resembled normal walking. BWSTT without additional
      therapist or self-support of the upper limbs was associated with more severe gait
      abnormality [Wilks' lambda = 0.20, F(6, 6) = 3.99, p = 0.047]. With the exception
      of therapist facilitation, the gait training conditions that achieved the closest
      approximation of normal walking required self-support of the upper limbs. When
      participants held on to a stable handrail, self-selected gait speeds were up to
      three times higher than the speeds obtained for over-ground walking [Wilks'
      lambda = 0.17, F(6, 7) = 5.85, p < 0.05]. The provision of stable upper-limb
      support was associated with high self-selected gait speeds that were not
      sustained when walking over ground. BWSTT protocols may need to prioritize
      reduction in self-support of the upper limbs, instead of increasing treadmill
      speed and reducing body weight support, in order to improve training outcomes.

PMID- 21174633
TI  - Simultaneous application of interstitial flow and cyclic mechanical strain to a
      three-dimensional cell-seeded hydrogel.
AB  - The present study describes the design and validation of a simple apparatus to
      apply simultaneous mechanical and fluidic stress to three-dimensional (3D) cell
      seeded collagen hydrogels. Constructs were formed in wells in a silicone
      substrate that could be stretched cyclically, and were also fitted with inlet
      ports to apply fluid flow. Acid etching was used to retain adhesion of the gels
      to the walls of the well, and an acellular layer of collagen hydrogel was used to
      distribute flow evenly. Finite element modeling showed that 5% uniaxial strain
      applied to the entire silicone substrate resulted in ~6.5% strain in each of the
      gel constructs. Permeability testing and flow observation showed that acellular
      hydrogels were fourfold more permeable than cardiac fibroblast-seeded gels, and
      that the fluid distributed evenly in the acellular layer before entering the cell
      seeded gel. Viability testing and imaging demonstrated that cells remained viable
      with expected fibroblast morphology for the 120 h duration of the experiments.
      These results demonstrate that this simple bioreactor can be used to study the
      effects of mechanical strain and interstitial flow in 3D protein hydrogels. Such
      3D tissue models have utility in studying cell and tissue responses to their
      mechanical environment.

PMID- 21174635
TI  - Thiolated polyacrylic acid-modified iron oxide nanoparticles for in vitro
      labeling and MRI of stem cells.
AB  - PURPOSE: The purpose of this study was to develop and characterize new surface
      modified iron oxide nanoparticles demonstrating the efficiency to be internalized
      by human endothelial progenitor cells (EPCs) from umbilical cord blood. METHODS:
      Iron oxide nanoparticles were coated with polyacrylic acid-cysteine (PAA-Cys) by
      either in situ precipitation or postsynthesis. The nanoparticles were
      characterized by X-ray powder diffraction. EPCs were labeled with PAA-Cys
      modified iron oxide nanoparticles or with uncoated nanoparticles. The relaxivity
      of uncoated and coated iron oxide nanoparticles as well as EPCs labeled with PAA
      Cys-modified iron oxide were determined. RESULTS: Addition of PAA-Cys increased
      the particle size from 10.4 to 144 and 197 nm, respectively. The X-ray powder
      diffraction pattern revealed that the particles consist of Fe(3)O(4) with a
      spinal structure. Postsynthesis coated particles showed a cellular uptake of 85%
      and 15.26 pg iron/cell. For both types of particles the relaxivity ratio was at
      least 2-fold higher than that of the gold standard Resovist((r)). CONCLUSION: The
      PAA-Cys coated iron oxide nanoparticles are a promising tool for labeling living
      cells such as stem cells for diagnostic and therapeutic application in cell-based
      therapies due to their high relaxivities and their easy uptake by cells.

PMID- 21174636
TI  - Research. Significant strides made in HIV/AIDS services but many obstacles
      remain.

PMID- 21174637
TI  - Policy.  HHS announces $30 million to support national HIV strategy.

PMID- 21174638
TI  - Immigration.  Government can't be held accountable for lack of HIV meds.

PMID- 21174639
TI  - SSI. AIDS did not significantly restrict man in daily living.

PMID- 21174640
TI  - Supervisor-subordinate age dissimilarity and performance ratings: the buffering
      effects of supervisory relationship and practice.
AB  - Using 394 pairs of employees and their immediate supervisors working in the
      Information and Communication Technology (ICT) sector in three northern European
      countries, this study examined the effect of workplace moderators on the link
      between relational demography and supervisor ratings of performance. Directional
      age differences between superior and subordinate (i.e., status incongruence
      caused when the supervisor is older or younger than his/her subordinate) and non
      directional age differences were used as predictors of supervisor ratings of
      occupational expertise. The quality of the supervisor-subordinate relationship
      and the existence of positive age-related supervisory practices were examined as
      moderators of this relationship. The results provide no support for a
      relationship between directional age differences and age-related stereotyping by
      supervisors in ratings of performance, neither for the effects of age-related
      supervisory practices. However, high quality supervisor-subordinate relationships
      did moderate the effects of age dissimilarity on supervisory ratings. The
      implications of these findings for performance appraisal methodologies and
      recommendations for further research are discussed.

PMID- 21174641
TI  - [Preterm infant follow-up program in Lombardy Region-- Italy].
AB  - The correct management of preterm babies requires, after discharge, an adequate
      follow-up program. The plan could be adjusted in relation to economical rises,
      rooms and staff amount of Neonatal Intensive Care Unit (NICU), varying its length
      and number of visits for patient for year. A survey was performed in Lombardy
      Region, Italy, to evaluate the differences among the various follow-up programs
      and to find a possible common approach suitable by all NICUs. A 23 questions
      formulated questionnaire, with multiple choice answers, has been sent to the
      referents of outpatients management of any NICU of the Region. The answers
      obtained from 13 of the 17 Units interviewed have been evaluated. All NICUs have
      a follow-up program, including ophthalmological, neurological, cardiac and
      audiometric evaluations. The plan length vary by 1 to 7 years; annually a mean of
      130, and daily a mean of 7.4 patients are visited. At discharge all NICUs provide
      a clinical report to the family, but it is mailed to the Primary Care Physician
      just in 54% of cases. The differences founded among the follow-up programs
      resulted not significant for the preterm management, therefore it is possible to
      uniform the different plans, improving communication and interaction between
      NICUs and Primary Care Physicians.

PMID- 21174642
TI  - [Celiac disease and "gluten sensitivity"].
AB  - It is known that celiac disease is characterized by a huge variety of clinical
      forms ranging from classical ones to silent forms, potential ones and to an
      increased number of cases of gluten-sensitivity. The latter is an abnormal non
      allergic sensibility to gluten. Clinical manifestations can be very different
      without a severe intestinal damage (Marsh/Oberhuber 0-I) and this condition seems
      to benefit from a gluten free diet. Cases of gluten-sensitivity appear very
      interesting in the search of histological markers with elevated specificity,
      which are able to identify slight and early gluten dependent enteropathy,
      especially in at risk patients for celiac disease even before classical
      autoantibodies appear: for instance, this is the case of intraepithelial
      lymphocytes T-cell receptor gamma delta and mucosal deposits of class IgA anti
      transglutaminase antibodies. Other studies are investigating transglutaminase
      isoenzimes (different from tissue one), that can be identified in patients with
      gluten dependent symptoms without classical autoantibodies. Forms of gluten
      allergy have a different pathogenesis from celiac disease and are represented by
      "backer's asthma" or by classical allergy to wheat proteins. Clinical
      manifestations can vary from anaphylactic reactions to dermatological,
      respiratory and intestinal symptoms. Also in these cases the therapeutic approach
      is based on gluten free diet.

PMID- 21174643
TI  - [Clinical pattern of pediatric acute gastroenteritis in the community].
AB  - Acute gastroenteritis (AGE) is a typical illness seen in outpatient children,
      usually treated by Family Pediatricians (FP). To analyze the characteristics of
      community AGE, we have collected all the case histories of children observed in a
      FP office, analyzing computerized clinical file (FIMED Infantia), taken from the
      period 2003-2007. We enrolled 1140 children with AGE were gathered, for an
      average of 228 cases/year; 578 (51%) males and 562 (49%) females; the month with
      highest number of cases is October (120 cases, 10.5%), followed by September and
      April (105 cases in both, 9.2%). The month with the lowest incidence is February
      (75 cases, 6.6%) followed by August (81 cases, 7.1%); children's mean age is 4.6
      +/- 3.4 years with a wide range (10 days divided by 16 years). As regards the
      clinical pattern, 314 children (27.5%) presented high fever, 395 (34.6%) vomiting
      and 24 cases (2.1%) bloody diarrhea; mean daily stools is 3.9 +/- 1.1; only 4
      children suffered from severe dehydration. 255 children (22.4%) received
      antibiotic prescription, mainly cotrimoxazole (51%), followed by cephalosporins
      (39%) and macrolides (10%); 893 children (78.3%) were prescribed probiotics. Oral
      rehydrating solution was always offered to all children, followed by normal diet
      and only 4 children (0.4%) need the administration of a lactose free formula.
      Mean duration of diarrhea was 3.4 +/- 1.7 days, only 10 children (0.9%) suffered
      from chronic diarrhea and only 2 children (0.2%) were hospitalized due to severe
      dehydration. In conclusion, the child that refers to the FP office, is often a
      child with minor symptoms, for whom admission is not required; he/she presents a
      regular course and slight complications.

PMID- 21174644
TI  - [Children with nocturnal enuresis: why several treatments?].
AB  - OBJECTIVES: The Authors intended to verify whether, in relation to nocturnal
      enuresis,the differentiation of therapies can influence the clinical outcome.
      METHODS: A total of 30 children suffering of nocturnal enuresis underwent a
      different treatment: 10 children were treated with a behavioral approach, 10
      children by alarm treatment, and 10 children with desmopressin. RESULTS: In all
      the children treated with desmopressin resolved their illness,while 10% treated
      by alarm and 20% treated with behavioral intervention persisted in symptom of
      enuresis. CONCLUSIONS: The differentiation of therapeutical approaches respond to
      peculiarities of children and their families considering that the disappearance
      of enuresis is highly probable.

PMID- 21174645
TI  - [The necessity for psychological support during critical moments in pediatric
      cardiology and cardiac surgery].

PMID- 21174646
TI  - [The reverse shoulder arthroplasty].
AB  - The reverse shoulder arthroplasty indications are cuff tears arthropaty, revision
      of anatomic prosthesis and traumatology. The reverse shoulder arthroplasty
      doesn't need a rotator cuff integrity to be functional. However, complications
      are not rare (dislocation, descellement, infection...). The patient selection has
      to be rigorous. In any case, patient must be older than seventy years.

PMID- 21174647
TI  - [Hyperlactataemia : not only useful in circulatory shock].
AB  - Hyperlactataemia, a marker of poor prognosis in intensive care patients, is most
      frequently found in cases of acute circulatory failure ; however, it may be due
      to factors other than cellular hypoxia. The level of blood lactate is determined
      by the balance between its production and its elimination, which can be
      influenced by various factors. For example, the influence of medication on blood
      lactate levels should not be underestimated, whether in anaesthesiology, with the
      use of propofol, or with certain anti-retrovirals in HIV seropositive patients.
      And in oncology, blood lactate can derive from anaerobic metabolism,
      characteristic of tumour cells. The differential diagnosis of hyperlactataemia
      can, therefore, sometimes be more complex than initially thought.

PMID- 21174649
TI  - [Biliary ileus: diagnostic and therapeutic aspects. Report of a case].
AB  - We report a rare case of small bowel gallstone obstruction in a patient with
      cholecystointestinal fistula. Diagnosis of this condition is usually difficult
      and only achieved at surgery. We review the radiological findings, particularly
      the CT findings, helpful for diagnosis: ectopic gallstone, biliary gas and
      fistula. Early preoperative diagnosis could reduce morbidity and mortality.
      Treatment is surgical with enterolithotomy. There is some controversy over the
      need to repair the fistula.

PMID- 21174648
TI  - [Gastric adenocarcinoma following "silastic vertical ring gastroplasty": case
      report].
AB  - OBJECTIVES: Bariatric surgery is considered as the most effective therapy for
      morbid obesity. But, each procedure carries both short-and long-term
      complications. And, it remains unclear if the late occurrence of gastric
      adenocarcinoma could be linked to bariatric surgery. We described a case of a
      female who developed a gastric adenocarcinoma after a silastic ring vertical
      gastroplasty (SRVG). METHODS: A 54-year-old female presented with postprandial
      vomiting, poor appetite, dysphagia and weight loss 10 year after a SRVG. A
      gastroscopy with biopsy disclosed a juxta-pyloric adenocarcinoma. No distant
      metastasis was found. After 3 cycles of neoadjuvant chemotherapy, a subtotal
      gastrectomy with Roux-en-Y anastomosis was performed. RESULTS: After the surgery,
      a minor anastomotic leak was treated conservatively and a parietal abscess was
      drained. The pathological studies demonstrated a T2bN1 adenocarcinoma with
      negative margins. Adjuvant chemotherapy was administered. At the last work up,
      the patient is disease-free. CONCLUSION: The association between a gastric
      adenocarcinoma and a bariatric procedure such as a SRVG is difficult to assess
      without a case-control or a cross-sectional study. Nevertheless, when new upper
      digestive tract complaints occur in any patient with an otherwise unremarkable
      bariatric surgery follow-up, the diagnosis of gastric cancer should be bear in
      mind.

PMID- 21174650
TI  - [Legislative frame and clinical trials in Lebanon].
AB  - In Lebanon, as in other developing countries, most of the clinical trials are
      achieved without considering any rule adopted in the industrialized countries,
      which causes serious ethical problems. This study aims to review the different
      Lebanese texts related to clinical trials in order to show the existing
      legislative frame, and to formulate suggestions that help the legislator defining
      better this activity. We reviewed and analyzed the Lebanese legislation related
      to the clinical trials especially the Lebanese law project about "therapeutic
      trials on human subjects" and conducted semi-directive interviews with actors
      from the society. RESULTS: We noticed a legislative gap in this domain,
      highlighting the fragility of the social link in the health domain, and
      reverberating negatively on the physician/physician, physician/hospital,
      physician/industrial and industrial/hospital relationships, in addition to many
      gaps affecting the skills of physicians-investigators. In spite of the promising
      institutional effort, the national frame of clinical trials does not seem to be
      sufficient regarding the ignorance of applied legislative texts, the industrial
      promoter's weight, and the pressures. This is applied to the absence of a
      powerful national coordinator, the inexistence of a pharmacovigilance system or a
      skillful authority for the sanitary security of health products, and the
      confusion in the concepts of medical ethics and deontology. In conclusion were
      presented for achieving improvements on many levels: an objective criticism of
      the law project proposed in 2002 followed by a call to review its content and
      improve it in order to reach an instructive and applicable global legislation ;
      an action that can be realized only through educating adequately the
      investigators, and informing the large public in order to guide the governors
      towards a legislation allowing people in Lebanon to "live well " with complete
      dignity.

PMID- 21174651
TI  - [A Belgian medical board during World War Two or the bad outcome of the law
      concerning the "Board of Medical Doctors" from 1938 (Second part)].

PMID- 21174652
TI  - [Left superior vena cava].

PMID- 21174653
TI  - [Was Neanderthal's gait similar to modern human's gait?].

PMID- 21174654
TI  - [Do-Not-Resuscitate Orders in intensive care].

PMID- 21174655
TI  - [Pedagogy and clinical medicine].

PMID- 21174656
TI  - [Treatment recommendations for adrenal metastasis of non-small cell lung cancer].
AB  - To evaluate the optimum treatment strategy for metastatic adrenal tumors derived
      from non-small cell lung cancer (NSCLC), we retrospectively analyzed 17
      consecutive cases (8 resection cases: 4 synchronous and 4 metachronous: 9 non
      resection cases: 3 synchronous and 6 metachronous) who received surgical
      resection for NSCLC. The patients included 12 males and 5 females with a mean age
      of 63.9 years. Of these, 9, 3, 2, 2, and 1 patient (s) were diagnosed as having
      adenocarcinoma, squamous cell carcinoma, pleomorphic carcinoma, large cell
      carcinoma, and adenosquamous cell carcinoma, respectively. The mean interval
      after lung resection and treatment of metachronous adrenal metastasis was 9.9
      months. The mean time to progression from treatment of metachronous adrenal
      metastasis to disease progression was 8.9 months. A survival analysis showed no
      significant prognostic difference between the patient age, gender, pathological
      stage, synchronous/metachronous classification, CEA, and site of metastases.
      However, patients who received an adrenalectomy had a more favorable prognosis.
      The 2-year survival of patients following resection versus those who did not
      undergo a resection for adrenal metastasis was 62.5 and 22.8%, respectively.
      These data indicate that metastatic adrenal tumors should be resected if the
      patient can tolerate surgery after appropriate selection.

PMID- 21174657
TI  - [Acute massive pulmonary thromboembolism treated with percutaneous
      cardiopulmonary support perioperatively].
AB  - A 57-year-old female was transferred to our hospital because of sudden dyspnea.
      She was hypotensive and hypoxic. Acute massive pulmonary thromboembolism was
      detected by echocardiography and computed tomography (CT). Before the operation,
      she fell into severe shock and needed cardiopulmonary resuscitation. We applied
      percutaneous cardiopulmonary support (PCPS), and performed emergency open
      embolectomy under total cardiopulmonary bypass. Because of the right ventricular
      failure, she could not be weaned from total cardiopulmonary bypass. PCPS was
      required again and used continuously during postoperative management. Her
      cardiopulmonary state improved gradually. PCPS was stopped at 6 days after
      surgery, and she was extubated at 14 days after surgery. PCPS was very useful for
      resuscitation and stabilization of the cardiopulmonary function for acute massive
      pulmonary thromboembolism perioperatively.

PMID- 21174658
TI  - [Preferable surgical approaches to the aortic root-arch in patients with
      functioning tracheostomy].
AB  - Preferable surgical approaches to aortic diseases occurring between the aortic
      root and the arch in patients with functioning tracheotomy or permanent
      tracheostomy are described for securing adequate exposure and avoiding
      postoperative mediastinitis. Case 1: A 41-year-old man with Marfan syndrome
      presented with chronic type A thrombosed aortic dissection and severe aortic
      valve regurgitation. He had had a functional tracheostomy for managing
      respiratory function due to traumatic spinal cord damage. The heart and the
      ascending aorta were shifted to the right side of the chest and showed a
      significant counterclockwise rotation. Therefore, the reverse L-figure approach
      of a right-sided 3rd intercostal anterior thoracostomy and lower midline
      sternotomy was performed for Bentall operation. Case 2: A 76-year-old woman
      presented with thoracic aortic aneurysm of 11 cm in diameter. She had had a
      permanent tracheostomy with total laryngectomy. Therefore, cram shell approach
      was performed for total arch replacement. The 2 cases had no postoperative
      mediastinitis. These approaches are recommended for aortic diseases occurring in
      the ascending aorta or the aortic arch in patients with functioning tracheotomy.

PMID- 21174659
TI  - [Lung transplantation for secondary interstitial pneumonitis caused by treatment
      for primary mediastinal diffuse large B-cell lymphoma].
AB  - A 34-year-old woman was diagnosed as primary mediastinal diffuse large B-cell
      lymphoma, treated by cyclophosphamide, doxorubicin, vincrisitne, prednisolone
      (CHOP) chemotherapy and radiation therapy, and received high-dose ranimustine,
      cytarabine, etoposide, cyclophosphamide (MCVAC) chemotherapy with autologous
      peripheral blood stem cell transplantation. Seven years after complete remission
      was achieved, she recognized dyspnea and was diagnosed secondary interstitial
      pneumonitis caused by chemotherapy and/or radiotherapy. Because her symptoms and
      pulmonary function got worsen gradually, she underwent lung transplantation from
      a brain death donor when she was 47-year-old. She has successfully rehabilitated
      and returned to her life without oxygen inhalation therapy.

PMID- 21174660
TI  - [Octreotide acetate for persistent cylothorax after descending aorta
      replacement].
AB  - Cylothorax is one of a hazardous complication after thoracic aorta replacement.
      In this paper, we report effectiveness of octreotide acetate for postoperative
      persistent cylothorax. A 59-year-old female was referred to our hospital for
      chest pain. Previously she underwent arch reconstruction following aortic root
      replacement due to aortic dissection. Computed tomography (CT) revealed acute
      dissection on dissected descending aorta. Urgent descending aorta replacement was
      performed. After surgery, massive chylothoracic pleural fluid was drainaged.
      Although conventional medical treatment was not effective, drainage of
      chylothoracic pleural fluid significantly decreased after administration of
      octreotide acetate. Although mechanism has not been fully investigated,
      octreotide acetate was effective for persistent cylothorax after descending aorta
      replacement.

PMID- 21174662
TI  - [Neurinoma arising from brachial plexus with intrathoracic extension resected
      through the second intercostal space].
AB  - A case of neurinoma arising from the right brachial plexus with intrathoracic
      extension was reported. The patient was a 41-year-old man who had an abnormal
      shadow in the right apical area on the routine chest X-ray examination. Magnetic
      resonance imaging (MRI) revealed that the mass had some features of benign
      neurinoma. The tumor was resected through the 2nd intercostal space under an
      axillary skin incision approach and diagnosed as neurinoma on histological
      examination. He had a complaint of hyperesthesia of the right upper arm for 2
      months postoperatively.

PMID- 21174661
TI  - [Cylindrical patch repair for circumferential subvalvular abscess due to
      prosthetic valve endocarditis].
AB  - A 51-year-old male underwent aortic valve replacement and vascular prosthesis
      implantation due to an aneurysm of the ascending aorta combined with aortic
      regurgitation caused by the bicuspid aortic valve. Semi-emergency surgery was
      performed due to severe paravalvular leakage with prosthetic valve endocarditis
      16 months after the 1st operation. The circumferential annular abscess cavities
      were closed with a cylindrical patch, and a mechanical valve was installed on the
      upper edge of the sutured cylindrical patch. A vascular prosthesis was
      reimplanted to the ascending aorta. Use of the cylindrical patch provides a good
      exposure of operative field to close circumferential annular abscess cavity.

PMID- 21174663
TI  - [Spinal cord infarction due to aortic dissection during coronary artery bypass
      grafting under percutaneous cardiopulmonary support].
AB  - We report a case of aortic dissection due to improper position of a percutaneous
      cardiopulmonary support (PCPS) cannula into the femoral artery during coronary
      artery bypass grafting (CABG). A 77-year-old man with 3-vessel disease underwent
      off-pump CABG (OPCAB). Blood pressure suddenly lowered during bypass grafting to
      the right coronary artery. PCPS was performed between the left femoral artery and
      the right atrium. Bradycardia occurred 37 min after initiation of PCPS, and
      transesophageal echocardiography revealed Stanford type A aortic dissection. By
      converting the perfusion site from the femoral artery to the right axillar
      artery, the false lumen disappeared and did not reccur after cessation of PCPS.
      Therefore, the aorta was not replaced. He had however, bilateral leg paralysis
      after surgery. Magnetic resonance imaging (MRI) revealed spinal cord infarction
      caused by aortic dissection. Computed tomography (CT) confirmed disappearance of
      the false lumen and no expansion of the aorta 1 month after surgery. Meticulous
      care should be taken of the site and size of the arterial cannula in the
      extracorporeal circuit in such cases.

PMID- 21174664
TI  - [Acute type A aortic dissection, developed shortly after aortic valve replacement
      and coronary artery bypass grafting].
AB  - We experienced a case of acute type A aortic dissection shortly after a cardiac
      operation. A 73-year-old man underwent aortic valve replacement and coronary
      artery bypass grafting for aortic regurgitation and angina pectoris. Aortic valve
      was tricuspid and the ascending aorta was mildly dilated in preoperative studies.
      The postoperative computed tomography (CT) revealed aortic dissection, from the
      ascending aorta to the arch of aorta, although the patient was asymptomatic.
      Reoperation for the aortic dissection was performed on the 22nd post operative
      day. Re-do sternotomy was safely carried out prior to heparinization. Under
      hypothermic circulatory arrest with femoral arterial and venous cannulations, the
      ascending aorta was replaced and re-implantation of the saphenous vein graft was
      carried out. The postoperative recovery was uneventful and he was discharged on
      the 17th postoperative day.

PMID- 21174665
TI  - [18F-fluorodeoxyglucose positron emission tomography (FDG-PET) negative poorly
      differentiated adenocarcinoma of lung with mediastinal lymph node metastases].
AB  - A 58-year-old woman was referred to our hospital for further medical examination
      of bilateral lung nodules on the chest computed tomography. Standardized uptake
      valve (SUV) max of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)
      were negative value at both lung nodules, but positive value (3.4) at a
      pretracheal lymph node. The size of the small lung nodule of the left lower lobe
      (S9) was unchanged, but the lung nodule of the right upper lobe (S1) was
      gradually enlarged. By the biopsy of the right lung nodule, the poorly
      differentiated adenocarcinoma was diagnosed pathologically. The right upper
      lobectomy with mediastinal lymph node dissection was performed. The metastasis
      was pathologically determined for FDG-PET positive lymph node. The most important
      reason for negative FDG-PET at primary lesion was considered that the expression
      of glucose transporter 1 (GLUT-1) was very few. FDG-PET has become a useful tool
      in the diagnosis of the pulmonary cancer, but we should understand its limitation
      and diagnose carefully.

PMID- 21174666
TI  - [Iatrogenic diaphragmatic hernia following partial resection of the lung via
      video-assisted thoracoscopy].
AB  - We report a case of iatrogenic diaphragmatic hernia following partial resection
      of the left lung via thoracoscopic surgery. A female in her 60s underwent partial
      resection of the left lung via thoracoscopic surgery on suspicion of primary lung
      cancer. The pathological finding was granuloma. Four months after surgery, she
      experienced pyrosis, and her radiograph showed a gastric bubble in the left
      thorax. Coronary-section computed tomography demonstrated that the gastric fundus
      had pushed into the left thorax. We performed elective video-assisted thoracic
      surgery because she did not show any symptoms. After the adhesiolysis, the
      herniated stomach was returned into the abdominal cavity, and the hernial orifice
      of the diaphragm was directly sutured. The postoperative course was uneventful,
      and the patient was discharged on the 12th postoperative day and is doing well.
      We should consider the possibility of iatrogenic diaphragmatic hernia following
      thoracic surgery during which an invasive technique involving the diaphragm was
      undertaken.

PMID- 21174667
TI  - [Posterior mediastinal paraganglioma].
AB  - We report a case of 26-year-old man with a posterior mediastinal paraganglioma.
      Although he was asymptomatic, chest abnormal shadow was pointed out by the
      regular medical screening with chest X-rays. A chest computed tomography (CT)
      showed a left posterior mediastinal tumor with strong enhancement. He was
      referred to our hospital for surgery. We tried a video-assisted thoracic surgery
      (VATS) for resection of the tumor, but additional small thoracoscopy was
      necessary for control of bleeding. The patient's vital sign was stable at
      perioperative course. The histopathological examination revealed no evidence of
      malignancy, and a final diagnosis of paraganglioma was made. His postoperative
      course was uneventful, and is currently doing well without sign of recurrence.
      Because metastasis and/or local recurrence of paragangliomas is difficult to
      predict accurately only by histopathological finding, long-term follow-up is
      thought to be essential after surgery.

PMID- 21174668
TI  - [Aneurysm of the aortic cusp; report of a case].
AB  - We performed surgical therapy to the rare case of the perforation of an aneurysm
      of the aortic cusp which had caused the congestive heart failure. 71-year-old man
      having developed coughing was diagnosed as a severe aortic regurgitation and came
      to our hospital for surgery. The non coronary cusp was dilated and perforated.
      The aortic valves were removed and replaced with a bioprosthetic valve. The
      pathological examination of the valves showed healed infective endocarditis. The
      patient discharged home uneventfully.

PMID- 21174670
TI  - [Mitral valve replacement for mitral valve stenosis and insufficiency in a
      patient with antiphospholipid syndrome and systemic lupus erythematosus; report
      of a case].
AB  - A 41-year-old woman complained of dyspnea due to pneumonia and congestive heart
      failure and was diagnosed as severe mitral stenosis and insufficiency. She was
      previously diagnosed as antiphospholipid syndrome (APS) because of previous
      pregnancy morbidity and cerebral infarction. Mitral valve replacement was
      performed with postoperative strict anticoagulant therapy and postoperative
      course was uneventful. Cardiac surgery in APS patients has been reported with
      high morbidity and mortality because of perioperative fatal thromboembolism. It
      is very important to initiate anticoagulant therapy with heparin immediately
      after the operation to prevent thrombosis.

PMID- 21174669
TI  - [Re-operation of an aortic pericardial bioprosthesis 23-years after implantation;
      report of a case].
AB  - A 49-year-old female suffered from dyspnea on exertion and jaundice from June,
      2009. She had undergone aortic valve replacement with Carpentier-Edwards
      pericardial bioprosthesis due to active infectious endocarditis 23-years
      previously. The echocardiography showed severe aortic stenosis with moderate
      regurgitation. She was diagnosed as having prosthetic valve malfunction. Re
      replacement of the aortic valve with mechanical valve was successfully performed.
      As far as we can see, this is one of the longest-term cases of implantation of
      pericardial bioprosthesis.

PMID- 21174671
TI  - [Coronary artery bypass graft for Bland-White-Garland syndrome in an old age;
      report of a case].
AB  - We report a case of Bland-White-Garland syndrome with advanced age. The patient,
      a 67-year-old women, presented with a history of congestive heart failure.
      Coronary catheterization revealed an anomalous origin of the left coronary artery
      (LCA) from the trunk of the pulmonary artery and huge right coronary aneurysm.
      Myocardial single photon emission computed tomography (SPECT) showed previous
      myocardial infarction with reversible ischemia in left anterior descending (LAD)
      region. We performed LCA direct closure and coronary artery bypass graft. The
      patient recovered uneventfully without signs of ischemia. Although a bypass graft
      was patent, left ventricular function had not been improved immediately probably
      due to the coronary flow pattern changes.

PMID- 21174672
TI  - [Catamenial pneumothorax; report of a case].
AB  - A 39-year-old woman was referred to our hospital because of pneumothorax related
      to menstruation. Chest X-ray showed right pneumothorax. Right thoracoscopy
      revealed 3 fenestrations on the diaphragm. Partial resection of the diaphragm
      including these lesions were performed. Intrathoracic minocycline was applied
      expecting pleural adhesion after surgery. Histopathological examination confirmed
      the presence of endometriosis on the resected diaphragm.

PMID- 21174673
TI  - [Organ transplantation network system].

PMID- 21174674
TI  - [Organ transplantation from the brain dead in Japan. Preface].

PMID- 21174675
TI  - [Evolution of organ transplantation in Japan].

PMID- 21174676
TI  - [Current status and issues of organ transplantation in Japan].
AB  - Since Organ Transplant Act was legislated and enforced in 1997, there reported to
      be 86 cases of organ donation from brain-dead donors, and 70 cases for heart
      transplantation, 67 for lung transplantation, 67 for liver transplantation, 64
      for pancreas transplantation and 103 for kidney transplantation as of the end of
      May, 2010. The organ donation from brain-dead persons in Japan required the
      documented will of the deceased to accept brain death and to remove his/her
      organs for the purpose of transplantation, and the written consent of his/her
      family member to brain death diagnosis and organ donation. Furthermore
      enforcement regulations and related guideline too much restricted and limited the
      necessary conditions for the organ donation from brain-dead donors. In 2009,
      Organ Transplant Act was amended, and after related regulations and guideline
      were revised, amended Organ Transplant Act was enforced in 2010, which provide
      that organ removal from brain-dead persons for the purpose of transplantation
      requires the written consent of his/her family member to brain death diagnosis
      and organ donation in case that there is no reason to believe that the deceased
      indicated any objection, in life, to organ donation and brain death, or in case
      that the deceased expressed his/her will in writing during his/her lifetime.
      Although the increase in the number of organ donation would be expected, it is
      considered to be indispensable to enlighten the public upon organ
      donation/transplantation, encourage that in those understanding and to minimize
      any burdens on donor hospitals as far as possible.

PMID- 21174677
TI  - [Comparison of organ transplantation between Japan and overseas countries-
      regarding new law of organ donation and transplantation].
AB  - In Japan, the new law of organ transplantation was introduced in 2010 as broad
      opt in system likely WHO standard. However option for organ donation from the
      patients with brain death is not regulated by the law and depends on the decision
      of charged doctors. Organ donation is prohibited from the child injured with
      child abuse and the patients with mental retardation. Directed donation is
      adopted in USA and Korea, although it is prohibited in all European countries. It
      is permitted only for pre-registered donors and their parents, children and
      spouse in Japan. Opt out system should not be established in Japan because it is
      still not enough that general people accept brain death. Recruit and education of
      more coordinators and ICU doctors and nurses are also necessary, in terms of
      donor action program. In addition we have to keep on enlightening organ donation
      for general people.

PMID- 21174678
TI  - [The Organ Transplantation Law].
AB  - The old Organ Transplantation Law was issued in 1997 and had never been revised
      for 12 years. Brain dead donors had to leave written consent to donate their own
      organs as well as their family consent. The organ donation from children under 15
      years old was prohibited. The majority of the patients in need of organ
      transplantation died of organ shortages in Japan. Many patients especially
      children had to travel abroad to receive organs. The amendment bill for the Organ
      Transplantation Law was passed in the House of Councilors on July 13, 2009. The
      new Organ Transplantation Law permit organ donation from brain dead donors who
      had not refused to donate their organs, as long as there is family consent.
      Children under 15 years old can become donors. This article explains the old and
      the new Organ Transplantation Laws and the course of the amendment.

PMID- 21174679
TI  - [How should we comprehend the guideline for the revised Organ Transplantation
      Law?].
AB  - In accordance with the revision of the "Organ Transplantation Law", the
      ordinances and the guideline for the law were also revised. The revision of the
      guideline, which finds legal basis on the circular notices, raises some issues
      about its position in the Japanese legislative system. It is quite ambiguous
      whether we should comprehend the guideline as the interpretation of the law, as
      the procedural guidance, or as the instruction within the administrative body.
      Thus, the legal obligation for the healthcare professionals to observe the
      guideline is also unclear. There are many issues about the transplantation law,
      the ordinances and the guideline. They include (1) Legal implication of the
      "brain death" (Is "brain death" absolutely synonymous with "death" ?), (2)
      Scientific relevance of the criteria for diagnosis of brain death, (3) Definition
      of the "adequate treatment" which is the prerequisite for diagnosis of brain
      death, (4) The time of death for the cases who were declared legally brain-dead
      but did not donate the organs, (5) By whom and when should the organ donation be
      proposed, and more. The ambiguity about the legal position of the guideline shall
      cause confusion in the scenes of clinical practice.

PMID- 21174680
TI  - [Organizing medical institutions for organ donation].
AB  - In spite of the fact that organ donation requires a substantial commitment in
      terms of personnel and time, the place most likely to become the center for organ
      donation is emergency medical departments, which are already under extreme
      pressure. However, it is often in emergency medical departments, where the
      everyday load of work is already substantial, that organ donation options are
      presented by medical staff in response to requests from families. Therefore, it
      is necessary to improve understanding of terminal care medicine, including brain
      death, in order to participate justly and fairly in organ donation after revision
      of the law. More importantly, the system of organization within hospitals must be
      improved in order to ensure support for emergency departments.

PMID- 21174681
TI  - [Brain death and death of human individual].
AB  - The revised Organ Transplant Law of Japan, enforced from July, 2010, has made
      "brain death", as well as "cardiac death", death of human individual and
      procurement of an organ from a brain dead body is now possible by a surviving
      family's consent. However, brain death issue is a still serious topic, and
      arguments are going around on whether it is morally justifiable to accept brain
      death, and if so, in what sense. The author argues that death of human being
      occurs when "vital triangle," consisted of brain, heart and lung, is severed out.

PMID- 21174682
TI  - [The concept of death in the revised Organ Transplant Law in Japan].
AB  - The Organ Transplant Law of Japan, enacted in 1997, did not allow organs to be
      taken from a brain-dead person unless he or she left written consent. The concept
      of brain death was controversial. It was a product of compromise that a brain
      dead person could be recognized as dead only if he/she had given consent to allow
      organs to be taken in the event of brain death. This law was revised in 2009. It
      became possible to take organs from a brain-dead person with the consent of the
      patient's family, even if the wishes of the person who died were not clear. This
      revision, which took effect in July 2010, also legalizes the removal of organs
      from brain-dead children under the age of 15. The author of this article
      considers whether and how the legal definition of brain death was changed through
      this revision.

PMID- 21174683
TI  - [Post Istanbul Declaration].
AB  - In May, 2008, the Istanbul Declaration calling for completely against organ
      traffic and for self-sufficiency in organ donation was presented by a Steering
      Committee convened by The Transplantation Society (TTS) and the International
      Society of Nephrology (ISN) under the cooperation with WHO. The chief principles
      are to spread cadaver transplant worldwide for prevention of improper organ
      donation, and to protect and secure living organ donors. On the other hand, in
      Japan brain-dead transplantation had been legalized in 1997. Since the first
      Organ Transplant Law went into effect without sufficient common view of brain
      death as legal death, autonomy of donor has taken top priority, and it imposed
      donors on preconditions to sign a donor card indicating the willingness to donate
      their organs. However, the lowest rate of organ donation has been kept annually.
      All heart transplant in children had been done in other countries. In 2009, the
      point issue of self-sufficiency in organ donation in the Istanbul Declaration
      directly affected the revised law in Japan. Now, the newly passed law reaches a
      world standard. It is a start line to reconsider the reason why the brain-dead
      transplant has not been accepted by Japanese society and to move self-sufficiency
      in organ donation. There is also a pressing need to develop new medical treatment
      or technology which requires no organ donation.

PMID- 21174684
TI  - [Japanese ethos and organ transplantation from brain-dead donors].
AB  - A trend observed since the 1980s in the Japanese academic scene is the
      overturning of Hippocratic ethics by American individualistic bioethics. However,
      the Japanese ethos is more sympathetic to personalistic bioethics rooted in
      Hippocratic ethics, which assumes the universal view of the 'interdependent self'
      clearly marked off from the 'independent self' specific to American culture. In
      Japan, organ transplantation from brain-dead donors is promoted despite the lack
      of consensus on whether brain death signifies death of the individual. From the
      viewpoint of personalistic bioethics, this situation is problematic because it
      violates the dictum primum non nocere of the Hippocratic Oath. We should
      therefore first establish consensus on brain death and then promote a 'culture of
      donation' based on human dignity.

PMID- 21174685
TI  - [Current status and future of organ transplantation in Japan].
AB  - When Organ Transplantation Law was issued, Japanese Organ Transplantation Network
      (JOT) was established. JOT plays a role in listing recipients, management and
      education of JOT coordinator(Co), publicity, and head-quarter at the time of
      organ donation. JOT Cos play roles in getting consent for organ donation from
      relatives, donor evaluation and management, organ transport, management of organ
      recovery and taking care of donor families during and after donation. Every
      prefecture has at least one own prefectural Co who is mainly working for public
      education and hospital development. They help JOT Co at the time of organ
      procurement. Most prefectures commission hospital staffs in procurement hospital
      to be an in-hospital Co, who find potential donors and support organ procurement.

PMID- 21174686
TI  - [The financial status and organization of the organ transplant system in Japan].
AB  - The Japan Organ Transplant Network is the only organization in Japan that
      maintains a waiting list for organ transplants and also functions as a
      procurement agency recovering organs. The yearly budget of fiscal year 2009 is
      692 million Japanese yen, 74% from government funding, and the rest from
      transplant center membership fees, potential recipient registration fees,
      transplant recipient coordination fees, and contributions. The registration fee
      is 30,000 yen for the first year, and 5,000 yen for every following year. The
      patient is also charged a coordination fee of 100,000 yen when receiving a
      transplant. As it becomes difficult to rely on government funding, we must
      discuss about the balance of funding from government and the expenses of the
      beneficiaries.

PMID- 21174687
TI  - [The certification and recruitment of the procurement coordinator].
AB  - In Japan, Japan Organ Transplant Network is responsible for the certification and
      recruitment of the procurement coordinators since April 1995. Individuals that
      have a medical license or are recognized to have similar knowledge, and who have
      passed an aptitude test including curriculum vitae, paper test, and practice
      assessment in an emergency unit, concluding in a recruitment interview are
      granted certification. As the Revised Organ Transplant Act has been enacted in
      2010, we predict the rise in donors, and also the importance of the role of the
      coordinators. In the future, a governmental certification is desirable, and it is
      urgent to train procurement coordinators by a professional and systematic
      training program.

PMID- 21174688
TI  - [Standard process of organ procurement].
AB  - As revised Japanese Organ Transplantation Law was issued on 17th July, 2010,
      standard process of organ procurement after brain death was changed as follows.
      After the patient is determined clinically brain dead, a doctor may tell his or
      her relatives the opportunity of organ donation and ask them whether they want to
      listen organ procurement by JOT coordinators. If they want to do so and to donate
      organs, brain death is determined by legally regulated method. Around this
      period, his or her organs are evaluated whether they are transplantable or not.
      After the patient was legally sentenced brain dead, transplant recipients are
      selected and procurement teams are sent from transplant centers. Organ function
      is evaluated again by procurement teams and then organs are procured and
      transplanted.

PMID- 21174689
TI  - [The role and perspective of recipient transplant coordinator in Japan].
AB  - The transplant recipient coordinator (RCo) has an important role in the clinical
      arena of organ transplantation for better patient management and successful
      outcome. In Japan, the step towards organization of RCo system has been in
      progress along with the increase of living-related liver transplantation as well
      as the start of transplantation from brain-dead donors. Considering its limited
      numbers and lack of national educational system, the Japanese Society of
      Transplantation recently has organized to start the new certification system for
      RCo setting prerequisites for application, educational programs and method of
      examination.

PMID- 21174690
TI  - [Current status of lung transplantation in Japan].
AB  - Between October 1998 and May 2010, 158 lung transplants were performed in seven
      centers in Japan. Living-donor lobar lung transplantation (LDLLT) has been
      performed more than cadaveric lung transplantation (CLT) because of the
      difficulty in obtaining brain dead donors (n = 93 versus n = 65). The indications
      were quite unique in Japan where idiopathic pulmonary arterial hypertension was
      the most common indication, followed by lymphangioleiomyomatosis, idiopathic
      interstitial pneumonia and bronchiolitis obliterans. The 5-year survival rate was
      81.4% in LDLLT and 68.6% in CLT (p = 0.104), which were much better than world
      average.

PMID- 21174691
TI  - [Heart transplantation].
AB  - Although the clinical outcome of heart transplantation in Japan is excellent in
      the past 11 years after establishment of the Organ Transplant Law, the total
      number of heart transplant is extremely limited in Japan, only 69 cases. The Law
      was revised and enforced in July 17, 2010, and pediatric heart transplantation is
      authorized in Japan from the legal point of view under the revised law. The most
      important revision of the law is that organs can be donated from brain death
      cadavers without written declaration of the donors themselves. We expect the
      number of the heart transplantation will be increased up to 30 to 50 cases per
      year, and social conditions are required also to be revised according to the
      revision of the Organ Transplant Law.

PMID- 21174692
TI  - [Liver transplantation].
AB  - Living donor liver transplantation (LDLT) had been started for pediatric patients
      since 1989, and indication of LDLT has been expanded to adult patients in
      concomitance with overcoming small-for-size graft. Recently, around 500 cases of
      LDLT have been performed annually, and outcome of pediatric patients after LDLT
      has been improved with more than 90% of patient survival rate. Deceased donor
      liver transplantation (DDLT) also had been started since 1999, however, annual
      number of DDLT remained less than 10 cases. Therefore, condition of liver
      transplantation in Japan is quite unique, which consist of more than 98% of LDLT
      and less than 2% of DDLT. Law of organ transplantation had been modified in July
      2010, which had been changed to world standard one.

PMID- 21174693
TI  - [Current situation of pancreas transplantation in Japan].
AB  - Pancreas transplantation has been recognized as the best treatment for advanced
      type 1 diabetic patients. In Japan, we have performed 64 SPK, PAK or PTA from 62
      brain-dead donors and two non-heart beating donors since the enforcement of Organ
      Transplant Act in 1997. In addition, 18 cases have been performed from living
      related donors. The patient survival, pancreas graft survival and kidney graft
      survival rate of the cadaveric transplantation at five years are 97.5%, 73.9% and
      71.0%, respectively. The QOL of the recipients in both mental and physical
      aspects has been wonderfully improved leading to the happy second life. In front
      of the revised low in this year, the number of the donor and the transplantation
      are expected to increase.

PMID- 21174694
TI  - [Current status and future of clinical kidney transplantation in Japan].
AB  - Kidney transplantation has been established to be the therapy for an end-stage
      renal disease. In Japan, living donor kidney transplantation is frequently
      performed (> 80%) because of a shortage of the deceased donors. The graft
      survival has been improved to 93.4% (5-year graft survival in living donor kidney
      transplantation after 2001). ABO-incompatible cases are increasing and more than
      20% are ABO-incompatible in Japan (30% in our institution). In our institution,
      225 kidney transplantations (182: living donors, 43: deceased donors) have been
      performed from 2004.4 to 2010.6. Although the graft survival is excellent,
      posttransplant infections including cytomegalovirus, EB virus and BK virus are
      problems which should be solved. For the safety of the recipients, we should use
      kidney grafts from brain-dead donors.

PMID- 21174695
TI  - [Current status and future perspective of clinical intestinal transplantation].
AB  - Results of intestinal transplant are improving in recent years and intestinal
      transplantation has been established as a therapeutic option for patients with
      intestinal failure associated with serious parenteral nutrition (PN) -related
      complications. According to the latest results from the Intestinal Transplant
      Registry (ITR), reported at the 11th International Small Bowel Transplantation
      Symposium held in Bologna, Italy in September 2009, the number of transplants was
      increasing every year and annually rose to 220 transplants per year. Recently one
      year graft survival rates achieved more than 80% and most of current survivors
      had stopped parenteral nutrition and resumed normal daily activities. As of
      September 2010, 20 intestinal transplants have been performed for 18 patients
      with intestinal failure in Japan. Eleven living-related segmental intestinal
      transplants (including 1 combined liver-intestine transplant) were performed,
      whereas six patients have received intestinal grafts from cadaveric donors.
      Fourteen of 18 patients are currently alive after transplant. This article
      reviews current status and future perspective in management of intestinal failure
      and clinical intestinal transplantation on the basis of our experience and recent
      publications.

PMID- 21174697
TI  - [Perspectives of pediatric liver and kidney transplantation in Japan].
AB  - In Japan, around one hundred and thirty pediatric living donor liver
      transplantations (LDLT) have been done every year, while cadaveric transplants
      are only 11 in the past 10 years. The indication has been extended to newborn
      babies as small as 2.5 kg of body weight. Five-year patient-survival of pediatric
      LDLT in Japan is 84.4%. Seventy pediatric kidney transplantations were done in
      2008, 59 from living and 11 from cadaveric donors. Ten-year graft survival is
      improving in recent cases, and it is 79.4% in cases done after 1992. Living donor
      kidney transplantation has been possible in children as small as 7 or 8 kg of
      body weight. With such a technical success, discussion to enhance the preemptive
      renal transplantation has been started in Japan.

PMID- 21174696
TI  - [Heart and lung transplantation in children--current status and perspectives].
AB  - In fact, pediatric organ donation and transplantation give a significant benefit
      to diseased children and their parents. During recent 3 years, the number of
      reported pediatric heart transplantation (HT) has remaining unchanged at 
      450/year, and the number of lung transplantation (LT) was reported around 90/year
      in the registry of ISHLT. The prognosis is not so different from that of adults,
      fifty % in LT and 75% in HT at 5 years. Dilated cardiomyopathy in HT and
      pulmonary arterial hypertension in LT are the most common diseases of
      indications. Important issues for all pediatricians include availability, and
      access to donor organ. The warm heart with gift of life or organ donation surely
      cure children suffered from intractable heart and lung diseases.

PMID- 21174698
TI  - [Diagnostic criteria of brain death for Japanese children].
AB  - In Japan, a revised act on organ transplantation is enforced from July 2010. This
      act enables an infant or a child with brain death to become a donor for organ
      transplantation under the consent of his or her family members. New diagnostic
      criteria have been set for children under six years of age. Diagnosis of brain
      death in infancy and childhood requires special caution, since an infant's brain
      has special features. The causes of brain death also vary according to the age.
      The new criteria exclude from candidates of donor neonates and infants under 12
      weeks of corrected age, as well as cases in which the possibility of child abuse
      cannot be completely denied. The time interval between two diagnostic procedures
      must be 24 hours or more.

PMID- 21174699
TI  - [Problems of the revised organ transplantation law for organ donation from
      child].
AB  - The revised organ transplantation law has been gone into effect from July, 2010
      in Japan. We discuss about the problems for organ procurement system from the
      point of a donor hospital. These problems are heavy burden for donor hospital and
      organ procurement from a donor of child. The criteria of brain death of child
      have to be established. And the donation of organ spends much time and requires
      many specialists. For example, it takes about more than 45 hours from the
      diagnosis of clinical brain death to the end of organ harvesting. To reduce a
      heavy burden for a donor hospital, supporting system have to be established for
      the donor hospital and the donor family. The organ procurement procedure is
      strictly regulated by the legal guidelines; we propose that the new framework is
      redesigned rapidly within the new law and the guidelines.

PMID- 21174700
TI  - [Family issues around brain death in children].
AB  - Introducing brain death of children in Japan, there are three major concerns such
      as a) difficulty of diagnosing brain death in children, b) difficulty of taking
      care of family of the brain dead, c) difficulty of eliminating child abuse
      victims from donors, which are expressed by hospitals and health care providers.
      These issues are strongly connected to scarce resources of pediatric intensive
      care medicine and PICUs in Japan. They handle most of these tasks in the United
      States. Not only facilitating transplant medicine, but providing appropriate
      medical care for children, PICUs are essential and indispensable.

PMID- 21174701
TI  - [The children organ transplantation and pediatric emergency medical system].
AB  - The revised Organ Transplant Law has eliminated the age restriction on donor,
      permits organ donation from brain-death children legally. At present, though,
      there are still many problems. We must remedy pediatric emergency medical system.
      Especially, we promote a number of children trauma centers as possible. And
      another thing, we establish distinct criteria for brain-death diagnosis of
      children, and support systems such as patient transportation and dispatch of
      specialists.

PMID- 21174702
TI  - [Organ transplantation and child abuse].
AB  - The revised 'Act Concerning Organ Transplantation' was enforced from July 17,
      2010, while the organ donation from a child under the age of fifteen became
      possible with the guardian's agreement. It is needed that construction of the
      auditing system to exclude organ procurement from the brain-dead child due to
      abuse and it is also important to defend child's right of making self-decision
      and expressing their will. However, the preparation period to establish the
      infrastructure until enforcing is not sufficient for about one year after
      revision by the Diet member legislation. This paper discusses various issues on
      current situations and problems to be solved which are associated with organ
      transplantation and child abuse in Japan, including flowchart and checklist for
      child abuse.

PMID- 21174703
TI  - [Health economics of transplantation system].
AB  - We arranged the main problem and the background factor of the transplantation
      from a viewpoint of health economics. As a result, we guessed that the people's
      recognition to public value of the transplantation system was low. And it was one
      of the fundamental factors to disturb the transplantation. In addition, we
      researched the explanation method and the case report about a health economics
      value of transplantation. According to the review, health economics value of
      transplantation should be accounted by cost-effectiveness (performance). Our
      country have to promote positively the transplantation, because the cost
      effectiveness (USA$/QALY and USA$/DALY) of the transplantation is high.

PMID- 21174704
TI  - [Diagnosis and treatment methods in recurrent miscarriage].
AB  - Recurrent miscarriage is classically defined as three or more consecutive
      pregnancy losses. Established causes of recurrent miscarriage are
      antiphospholipid antibodies, uterine anomalies and abnormal chromosomes in either
      partner, particularly translocations. Embryonic aneuploidy is the most important
      cause of miscarriage before ten weeks' gestation. It can be speculated that about
      51% of patients with a history of three miscarriages experienced these because of
      abnormal embryonic karyotypes. It is not necessary to give any medication for
      such cases caused by an abnormal embryonic karyotype. Psychological support might
      be the most important requirement to continue conceiving till live birth results.

PMID- 21174705
TI  - [New diagnostic criteria for diabetes in Japan].

PMID- 21174706
TI  - [Dedicated senior surgeons can get young surgeons].

PMID- 21174707
TI  - [Management of clinical nutrition in gastroenterological surgery--the present
      conditions and outlook in Japan].

PMID- 21174708
TI  - [Present status and future prospects of nutritional support teams].
AB  - Academic interest in nutritional support teams (NSTs) has increased rapidly in
      Japan since 1999, when they were first planned by the Japanese Society for
      Parenteral and Enteral Nutrition (JSPEN). The JSPEN promoted their use
      extensively after 2006 when extra medical fees were approved for medical
      management by NSTs under the national health insurance system. The purpose of
      NSTs is to provide the best nutritional support to patients who are malnourished
      or at high risk of developing malnutrition, without causing conflict among
      different medical staff. NSTs offer appropriate medical support and help prevent
      the deterioration of patients' health. The teams are comprised of specialized
      medical staff with nutritional expertise who work at the bedside and are
      committed to establishing good medical practice. The main targets of NSTs are
      patients who undergo surgery or are being treated in a geriatric or internal
      medicine unit, including those with lifestyle-related diseases. Therefore, most
      targets of NSTs are patients with common conditions. A package medical system
      based on the diagnostic-procedure combination was established, and regional
      medical centers were integrated to ensure high-quality medical care throughout
      Japan. Under this system, NSTs are expected to resolve individual patients'
      dietary issues. In addition, improvement of medical care quality and the training
      of reliable medical staff are necessary to provide nutritional management in the
      clinical setting. It will be necessary to the revise the assessment of NSTs as
      proposed by a committee of the Japanese Nutritional Support Promotion Group or to
      carry out surveillance to evaluate the outcomes of NST activity.

PMID- 21174709
TI  - [Nutritional support to prevent infectious complications after surgery].
AB  - The nutritional condition of patients affects the results of surgical treatment.
      In patients in poor nutritional condition, postoperative complications, length of
      hospital stay, and mortality rate were reported to increase. Perioperative
      nutritional management is an important factor in preventing the incidence of
      postoperative infectious complications. The assessment of nutritional status is
      also important, and the appropriate dietary regimen should be selected based on
      the results of the assessment. Oral and enteral nutrition are usually selected
      for perioperative patients. Early enteral nutrition is advantageous in preventing
      postoperative infection. The effects of immunonutrition and synbiotics in
      surgical patients have been discussed in many recent reports. The advantages and
      disadvantages of nutritional therapy must be understood to provide the most
      appropriate regimen. This paper reviews the contribution of nutritional support
      to the prevention of complications after surgery.

PMID- 21174710
TI  - [Points in nutritional management of the elderly].
AB  - The most important aim of nutritional management in the elderly is to maintain
      the strength of skeletal muscle and ability to perform activities of daily living
      (ADL). The total energy expenditure (TEE) decreases with age and accelerates
      after the age of 65 years. Impaired glucose tolerance becomes progressively more
      common with advancing age. On the other hand, healthy elderly people have a
      capacity similar to that of healthy young people to clear and oxidize a
      triacylglycerol load. Consequently, fat appears to be a more suitable fuel for
      the elderly than glucose. It is recommended that the elderly have a higher
      protein intake compared with young adults to maintain skeletal muscle. The TEE of
      the elderly is 20-25 kcal/kg/day, and the recommended daily allowance of protein
      is 1.0-12 g/kg/day. Furthermore, the ratio of fat in nonprotein calories should
      be the same as that for young adults. Eating fruit and vegetables can prevent the
      development of cancer. However, most elderly individuals do not take the time to
      prepare and eat fruit and vegetables regularly. Elderly people whose ability to
      perform ADL is impaired should undergo rehabilitation. Unnecessary rest should be
      avoided during inpatient rehabilitation. Impairment of the ability to perform ADL
      due to iatrogenic factors or an inappropriate understanding of the elderly
      metabolism must be avoided.

PMID- 21174711
TI  - [Pre- and postoperative nutritional support in upper disgestive tract surgery].
AB  - Patients undergoing upper digestive tract surgery are at risk for malnutrition
      and must be supported with careful nutritional management after a thorough
      assessment is performed. Parenteral nutrition is suitable for patients who cannot
      be fed enterally. However, total parenteral nutrition (TPN) has several metabolic
      disadvantages and affects the function of the gastrointestional tract. Both
      enteral nutrition and TPN can be combined for patients undergoing
      gastrointestinal surgical procedures. Immune-enhancing diets (IEDs) are useful
      for patients who have moderate to severe malnutrition due to postoperative
      inflammatory complications and poor motility. They should be supported with an
      IED for at least 5 days. However, postoperative IEDs have not shown benefits for
      those patients in a meta-analysis. Recently, there have been reports that
      intensive insulin therapy to maintain normal glucose levels in useful in the
      management of critically ill patients. Maintenance of normal glucose levels is
      difficult in the clinical setting because hypoglycemia is extremely dangerous for
      patients, and the NICE-SUGAR study showed that intensive insulin therapy
      significantly increased the risk of hypoglycemia. Postoperative management using
      TPN combined with enteral nutrition is recommended in patients who undergo
      invasive surgery for the treatment of upper gastrointestinal tract cancer.

PMID- 21174712
TI  - [Present state and views of nutritional management in abdominal surgery. 5. Pre
      and postoperative nutritional management of various diseases. (b) Hepatobiliary
      pancreatic disease].
AB  - The field of hepatobiliary-pancreatic surgery involves performing hepatectomy,
      pancreatectomy, and hepatopancreatoduodenectomy, which are all very invasive
      procedures. Since bile and pancreatic juice are associated with the etiology of
      disease, appropriate management is necessary for patients with chronic hepatitis,
      liver cirrhosis, obstructive jaundice, deteriorating internal and external
      secretory function of the pancreas and digestive organs, and absorption
      disorders. Because malnutrition increases the risk of postoperative morbidity and
      mortality, it is important for patients to maintain good nutritional status
      during the perioperative period to improve the postoperative outcome. Recently,
      the efficacy of branched-chain amino acid administration for liver cirrhosis,
      bile replacement for obstructive jaundice, early enteral nutrition,
      immunonutrition, and synbiotics has been reported and therefore these management
      approaches should be considered carefully in patients undergoing hepatobiliary
      pancreatic surgery.

PMID- 21174713
TI  - [Perioperative nutritional management in various clinical condition: diseases of
      lower digestive system].
AB  - The systemic inflammation-related nutritional nutritional index based on
      circulating levels of C-reactive protein and albumin can determine which
      colorectal cancer patients are vulnerable not only to tumors in which
      uncontrolled upregulation of the local interleukin (IL)-1-IL-6 network occurs but
      also to a specific tumor-acquired deleterious response that has developed or is
      developing in the host. These patients may first require a therapeutic strategy
      to control the IL-1-IL-6 network system in the tumor, both to reverse IL-6
      induced metabolic alterations to regain body mass during nutritional support and
      to benefit from adjuvant anticancer therapy by increasing the tumor response to
      treatment and reducing treatment-related adverse reactions. The early detection
      of this critical manifestation allowing for early intervention is important.
      Although further prospective studies are required to confirm our results, the
      findings reported here suggest that specific targeting of the IL-1-IL-6 pathway
      may be a promising new approach for the treatment of cancer-related cachexia.

PMID- 21174714
TI  - [National Clinical Database: program and participation].

PMID- 21174715
TI  - [What we can learn from a case of medical malpractice--the case of the repetition
      characteristics postoperative ileus that hemostasis with emergency laparotomy
      enforced to intraabdominal bleeding after appendectomy].

PMID- 21174716
TI  - [Breast reconstruction with expander and implant--primary expander placement].

PMID- 21174717
TI  - [Questionnaire with regard to extension of nurse's task during perioperative
      management].

PMID- 21174718
TI  - [A survey on nurse in our hospital regarding perioperative non-physician
      healthcare provider].

PMID- 21174719
TI  - [A survey on surgeons in our hospital regarding perioperative non-physician
      healthcare provider].

PMID- 21174720
TI  - [Molecular targeted therapies for patients with advanced thyroid cancer].

PMID- 21174721
TI  - [The effects of dietary calcium and protein intake on changes in bone mineral
      density during early and late stages of pregnancy].
AB  - OBJECTIVE: The study was performed to examine the effects of calcium (Ca) and
      protein intake on changes in bone mineral density during early and late stages of
      pregnancy, including the relationship to bone metabolism. SUBJECTS AND METHODS:
      In 40 pregnant women, bone mineral density (BMD) was measured three times: at 11
      16 weeks of gestation, at 24-28 weeks and within one week postpartum using
      ultrasonic bone densitometry. Bone metabolic markers in urine and serum were
      measured at the same time points. Ca and protein intakes over a three-day period
      were analyzed in relation to changes in BMD during the early and late stages of
      pregnancy, as well as to bone metabolic markers. Nutrient intake was adjusted for
      energy intake. Stiffness calculated from the combined value of the speed of sound
      transfer and broadband ultrasound attenuation was used as an index of BMD.
      RESULTS: Ca intake was positively correlated with change in BMD, whereas protein
      intake was negatively correlated in early and late stages of pregnancy. The
      extent of bone loss adjusted for Ga intake was significantly greater in women
      with a higher protein intake. In the early stage, Ca intake showed a positive
      correlation, whereas protein intake showed a negative correlation with the serum
      calcium/phosphorus ratio. In the late stage, Ca intake showed a positive
      correlation with bone alkaline phosphatase/urinary N-terminal cross-linking
      telopeptides of type I collagen ratio. CONCLUSION: These findings suggest that an
      increase in dietary Ga intake in both early and latestages of pregnancy may be
      important to maintain BMD during pregnancy. An increase in Ca intake in relation
      to greater protein intake may be necessary to prevent bone loss during pregnancy.

PMID- 21174722
TI  - [School-attendance problems, subjective symptoms and lifestyle factors: the
      Shizuoka health and lifestyle survey of students].
AB  - PURPOSE: This cross-sectional study was conducted to examine the prevalence of
      students with a sense of not wishing to-attend school, and associations with
      subjective symptoms and lifestyle factors. METHODS: The database of the Shizuoka
      health and lifestyle survey of students conducted in November 2003 was used. The
      subjects were 5448 elementary, junior high and high school students and 1051
      caregivers of elementary school students. A self-administered questionnaire was
      administered to obtain infiromation on non-willingness to-attend school,
      subjective symptoms and lifestyle factors for students and lifestyle factors for
      caregivers. RESULTS: Valid responses were obtained from 2675 elementary school
      students, 940 junior high school students, 1377 high school students and 659
      caregivers. The prevalence of students who experienced unwillingness to attend
      school in males was 11.4% in elementary schools, 12.1% in junior high schools and
      25.3% in high schools. The prevalences in females were 9.8%, 19.6% and 35.9%,
      respectively. Multiple logistic regression analysis with such unwillingness as
      the objective variable and subjective symptoms and lifestyle factors as the
      explanatory variables, stratified by school and sex, adjusted for school grade in
      elementary schools, showed significantly high odds ratios (ORs) for reduction of
      vitality (OR: 3.68-8.22), irritable moods (OR: 3.00-6.30), feelings of fatigue
      and weariness (OR: 3.63-5.10) and difficulty waking up in the morning (OR: 1.98
      2.69) in each school and sex, with an additional strong tendency for weight loss
      (OR: 1.83-2.97), with insignificantly high OR of boys in junior high schools (OR:
      2.09, 95% Confidence interval: 0.95-4.60). No significant association was found
      between unwillingness to attend school in elementary school students with the
      lifestyle factors of their caregivers. CONCLUSIONS: There was no gender
      difference in the prevalence of students with feeleings of unwillingness to
      attend school in elementary school students, but figures were higher in females
      than in males for junior high and high school students. This was associated with
      the same subjective symptoms as those observed for students actually not
      attending school.

PMID- 21174723
TI  - [Validity of a standard questionnaire to assess physical activity for specific
      medical checkups and health guidance].
AB  - PURPOSE: This study aimed to determine the validity of a standard questionnaire
      to assess amount of physical activity (PA) and cardiorespiratory fitness
      (VO2peak). METHODS: A total of 483 men and women, aged 20 to 69 years,
      participated. The standard questionnaire included 3 items about exercise, PA, and
      walking speed. All questions were designed to require an answer of Yes or No.
      Subjects were classified into one of four groups regarding the number of Yes
      answers to the three questions, giving activity levels of 0 to 3. The amount of
      PA was measured objectively with a tn-axial accelerometer which could also
      calculate daily step counts, and the amounts of PA under 3 metabolic equivalents
      (METs) and at 3 METs or more. VO2peak. was measured by incremental cycle exercise
      tests with indirect calorimetry. RESULTS: The daily step counts, the amount of PA
      at 3 METs or more, and the VO2peak. were significantly higher in subjects who
      answered Yes to each question than in those who answered No. Sensitivity and
      specificity of each question were 62-73% and 45-71% for the amount of PA
      established with the "Exercise and Physical Activity Reference for Health
      Promotion 2006 (EPAR2006)". The sum of sensitivity and specificity was the
      highest when the cutoff value was activity level 2 (sensitivity 73%, specificity
      68%). Sensitivity and specificity for VO2max established by EPAR2006 were lower
      than those for the amount of PA. CONCLUSION: These results suggest that only
      answering simple questions with a standard questionnaire is sufficient for
      estimation of PA levels for specific medical checkups and health guidance, even
      though the accuracy is somewhat limited.

PMID- 21174724
TI  - [Program development to promote network building between disciplinary agencies
      and informal community organizations].
AB  - OBJECTIVE: To develop a program that promotes network building between
      disciplinary agencies and informal community organizations (RIO) comprising
      community residents. METHODS: Questionnaire and interview surveys were conducted
      for the staff of a community comprehensive support center in order to assess the
      needs regarding network building with ICOs. Then, a program was developed based
      on the social cognitive theory. The aim of the program was to raise awareness
      about network building and to develop necessary skills. RESULTS: The program
      induded ten sessions, with themes encompassing "reviewing the past activities",
      "understanding the significance of network building with IGOs", "integrating the
      aims and visions of staff", and "learning ways to build networks with IGOs".
      Objectives of each session were set on the basis of the particular theme covered.
      Participants performed group work during the sessions. CONCLUSION: Establishment
      and actual implementation of programs in clinical practice could be expected to
      strengthen networking between disciplinary agencies and ICOs. It is necessary to
      implement programs and evaluate their effectiveness in the future.

PMID- 21174725
TI  - [Evaluation of a program to promote network building between disciplinary
      agencies and informal community organizations: trial in a community comprehensive
      support center].
AB  - OBJECTIVE: To examine the effectiveness of a program promoting network building
      between disciplinary agencies and informal community organizations (IGOs)
      comprising community residents, by implemention with staff of a community
      comprehensive support center (CJCSG). METHODS: The program was implemented for
      nine staff of a GGSG in Setagaya Ward, Tokyo for a year. For process evaluation,
      items were assessed concerning the contents of the program such as satisfaction
      and understandability, participants' goal attainment level at each period of the
      program, and program satisfaction as a whole. Outcome evaluation included
      measurement of participants' self-efficacy regarding network building with ICOs
      before and after the program, using interviews of the members who completed the
      program. RESULT: Eight out of the nine participants completed the program. All
      positively evaluated the contents of the program and their own goal attainment at
      each period of the program. After its completion, they felt highly satisfied.
      Moreover, there was an improvement in the cognition of the participants,
      including self-efficacy on network building with IGOs and the atmosphere in the
      GGSG with regard to network building. CONCLUSION: The efficacy of this program
      could be confirmed as demonstrated by the staff of the CCSC, although a more
      detailed assessment of validity and effectiveness will be necessary in the
      future.

PMID- 21174726
TI  - [Effects of a specific health guidance program for prevention of diabetes].
AB  - PURPOSE: A follow-up survey was carried out to examine the effects of a health
      guidance program by comparing data before and after the intervention. METHODS:
      The subjects comprised 20 potential diabetes patients aged between 40 and 64
      years who were covered by health insurance and underwent a basic health check-up
      between August and September 2007. They were given detailed advice on health
      promotion for six months. We compared the results of a questionnaire survey,
      designed to examine their lifestyle habits and health awareness, and a blood test
      with changes over time. At the end of follow-up training, we conducted a semi
      structured group interview to examine their lifestyles. RESULTS: At the
      completion of the program, decreases in body weight, BMI, abdominal
      circumference, T. G., and HbAlc were marked (P < 0.05). However, the one-year
      follow-up survey could not be completed for the majority of the subjects and
      values for blood and other parameters showed no or little change from those
      measured prior to the start of the program. One year later, we interviewed the
      group, and the results were grouped into eleven categories. CONCLUSION: The six
      month guidance program was effective at reducing BMI, HbA1c, and other relevant
      parameters. Within a year, however, return to close to the levels at the start of
      the program was noted. Although most subjects obtained support from their spouse,
      they did not change their dietary habits because it was difficult for them to
      seek cooperation from other family members. Thus, it is necessary to improve
      skills required for health advice.

PMID- 21174727
TI  - [The role of sulfated glycosaminoglycans in early mouse development].

PMID- 21174728
TI  - [Neurophysiological findings in psychiatric disorders].

PMID- 21174729
TI  - [Glucocorticoid treatment for cochlear ischemic and acoustic injuries].
AB  - The effect of glucocorticoids on sensorineural hearing loss of sudden onset
      remains to be controversial although glucocorticoids have been used for treatment
      of sudden sensorineural hearing loss. We review recent findings about the effect
      of glucocorticoids on cochlear ischemic and acoustic injuries obtained from
      animal experiments. Systemically administered glucocorticoids penetrate the blood
      cochlear barrier well. Glucocorticoids ameliorated the cochlear ischemic and
      acoustic injuries at a relatively wide range of doses, and they protect cochlear
      hair cells in these types of injury. The therapeutic actions of glucocorticoids
      in cochlear injuries were considered to be mediated via both genomic and non
      genomic pathways. Based on the results obtained in acoustic injury, therapeutic
      time window of glucocorticoids is considered to be short after the onset of
      injury. These findings obtained from animal experiments are important in
      considering clinical usage of glucocorticoids for the treatment of sensorineural
      hearing loss.

PMID- 21174731
TI  - [Internet information availability about facial nerve paralysis].
AB  - INTRODUCTION: The Internet is widely used to find medical information. Facial
      nerve paralysis, with its numerous, varied diagnoses and broad field expertise in
      otorhinolaryngology and other departments, has triggered countless sites with
      widely varying quality and reliability. We clarified concerns on Internet-related
      information availability on facial nerve paralysis. METHODS: We reviewed
      information using Japanese and English search terms for "facial nerve paralysis,
      facial palsy" on Google Japan (GJ), Yahoo Japan! (YJ), and Google USA (GU),
      clarifying the top 50 Web sites. RESULTS: GJ and YJ search results showed few
      public institution Web sites, whereas those of commercial acupuncture and
      moxibustion practitioners accounted for about 40% of all the sites. GU sites
      generally described differential diagnoses well, with extensive, accurate
      information mainly developed by Western-medicine doctors rather than acupuncture
      and moxibustion practitioners. CONCLUSIONS: The quality of facial nerve paralysis
      information on the Internet varies widely, with Web sites containing reliable,
      extensive information, especially those developed by public institutions, greatly
      lacking as of this writing.

PMID- 21174730
TI  - [Voice restoration and long-term progress in voice rehabilitation using the
      Provox2 voice prosthesis after total laryngectomy].
AB  - From January 2000 to December 2008, we conducted voice rehabilitation using the
      Provox2 voice prosthesis total-laryngectomy subjects. Of these, 36 attained
      restoration of 90.0%. Mean maximum phonation time (MPT) was 14.5s, ranging from
      MPT was not influenced by age, radiotherapy use, primary tumor site, or
      reconstructive surgery use. Voice prosthesis replacement averaged 25 weeks (5.8
      months), ranging from 9 to 74 weeks. Complications occurred in 16 caces (40.0%),
      mainly granulation tissue formation and prosthesis-site infection, also
      aspiration pneumonia, prosthesis-site salivary leakage, inability to replace the
      prosthesis, tracheomalacia, bodies in the trachea. Management rather than medical
      problems included cost, frequent hospital visits, and lack of motivation to use a
      prosthesis. The Provox2 voice prosthesis speech provides a higher rate of speech
      restoration, longer phonatory better intelligibility. Management problems,
      however, require that we work to understand subjects' living environments and
      family situations better for evaluating Provox2 voice prosthesis indication more
      effectively.

PMID- 21174732
TI  - [Two cases of intractable malignant external otitis with skull base osteomyelitis
      alleviated by intraarterial antibiotic administration].
AB  - Malignant external otitis (MEO) is a devastating external auditory canal
      infection usually occurring in the elderly with diabetes. MEO often progresses to
      potentially lethal skull base osteomyelitis (SBO) complications such as
      meningitis or multiple cranial nerve palsies. Poor vascularity in affected tissue
      due to diabetic microangiopathy and Pseudomonal infection is thought responsible
      for refractory infection. We conducted intraarterial antibiotic infusion (IA) in
      the external carotid artery of two subjects with intractable MEO deteriorating
      after long-term intravenous antibiotic administration with surgical debridement.
      IA raised the antibiotic concentration in infectious tissue. Clinical MEO
      manifestation was relieved just after starting IA, and IA therapy was followed by
      additional long-term intravenous and oral antibiotic administration, dramatically
      improving MEO while leaving only minimal infection at the skull base. These
      results demonstrate IA effectiveness in treating refractory MEO.

PMID- 21174733
TI  - [Analysis of Koch's phenomenon by BCg vaccination with the multi-puncture method
      in Japan].
AB  - PURPOSES: In Japan, BCG vaccination without a prior tuberculin skin test was
      started in 2005. Koch's phenomenon is well known as a skin reaction that appears
      within a few days at the BCG vaccination site if the vaccination is given to a
      person infected with tuberculosis. However, little has been known regarding
      Koch's phenomenon in cases where BCG is administered by the multi-puncture
      method. All doctors who observe Koch's phenomenon are requested to provide a
      report to the local government, which then transfers the report to the Ministry
      of Health, Labour, and Welfare. The purpose of the present study was to clarify
      the issues and challenges regarding Koch's phenomenon in Japan. METHODS: We
      analyzed a total of 814 reports of Koch's phenomenon submitted between April 2005
      and March 2009. The results were redefined in this study as follows. Non-specific
      reaction: Cases that we judged to not be infected with M. tuberculosis (not true
      Koch's phenomenon). This category includes cases classified as "follow up" on the
      report with a negative PPD result. Follow-up with positive tuberculin test: Cases
      that were highly suspected to be infected from a positive tuberculin test but
      that were followed up without treatment. This category includes cases in which
      treatment was recommended but was refused by the guardians. Koch's phenomenon:
      Cases that were treated as latent tuberculosis infection or disease. Referred to
      other hospital: Cases that were referred to another hospital and their final
      outcomes are not known. Unknown: Cases for which the final outcomes are not known
      due to a lack of information. RESULTS: The age at vaccination from 3 to 6 months
      in most cases, with an average age of 4 months (124 days). Skin reactions were
      noticed within 3 days in most (95.6%) of the cases. No serious reactions due to
      Koch's phenomenon were reported. The numbers of reported cases and the rates by
      the number of births were quite diverse among prefectures. The results for the
      reports were as follows: non-specific reaction: 578 (71.1%); follow-up with
      positive tuberculin test: 34 (4.2%); Koch's phenomenon: 106 (13.0%); referred to
      other hospital: 54 (6.6 %); unknown: 44 (5.4%). DISCUSSION: The differences in
      the number of reports by prefecture may partially be explained by differences in
      the risk of infection, but mostly by human factors such as: 1) explanation of
      Koch's phenomenon to guardian at the time of vaccination; 2) reaction to
      notification from guardian; 3) report system from doctor in charge to MHWL etc.
      The results showed a trend toward a steady decrease in the non-specific reaction
      over the 4-year period. When BCG direct vaccination was started in 2005, health
      professionals were not aware that a mild skin reaction at the vaccinated site
      could appear and then fade out within a few days without any special reason.
      Almost all the noted skin reactions in the first year were reported. It is now
      known, however, that such non-specific reactions can appear together with a
      negative tuberculin skin test and then fade out within a few days. The incidence
      of a "true" Koch's phenomenon (cases treated as LTBI or disease as well as cases
      diagnosed as LTBI but for which treatment was refused by guardians) was less than
      estimated based on the annual risk of infection. This result is probably due to
      the following: 1) some cases with a risk of infection do not receive the BCG; 2)
      a final result was not obtained in 12.0% of the cases, which must include a
      certain number of cases with a "true" Koch's phenomenon; 3) skin reactions were
      sometimes missed by guardians; 4) a proper diagnosis was not made for a suspected
      case; 5) the actual risk of infection in infants aged less than 4 months is less
      than estimated. CONCLUSION: Accurate information regarding Koch's phenomenon
      should be provided to guardians as well as doctors and/or health workers in
      charge of BCG vaccinations.

PMID- 21174734
TI  - [Present activity of BCG and LTBI treatment for infants in Japan].
AB  - I analyzed the BCG vaccination and treatment of latent tuberculosis infection
      (LTBI) for infants notified in 2008 in Japan. BCG was not recommended and
      treatment of LTBI was the main activity for prevention of TB in infants from
      birth to age 2 months. The majority of notified LTBI cases were detected by
      contact surveys. Out of the estimated number of TB infected (148), only 2 cases
      were notified based on the outcome of LTBI treatment for 89 infants. When the
      infants were 3-5 months old, both BCG vaccination and LTBI treatment were
      implemented. BCG coverage was 61.5-97.7%, and LTBI treatment for non-vaccinated
      individuals was applied for a larger number of infants (1.04 to 7.82 times as
      many) than the estimated number of infants infected with TB. The majority of
      infants were BCG vaccinated when they were 6-11 months old. Although LTBI
      treatment coverage was low, only 5 cases developed among those receiving BCG
      vaccination. During 1-2 year, BCG coverage was high and breakdown rates of BCG
      vaccinated children were much lower than those of non-vaccinated children. This
      difference might be due to not only the preventive effect of BCG but also risk
      difference of TB infection between BCG-vaccinated and BCG non-vaccinated
      individuals. The number of notified LTBI treatment cases was lower than the
      estimated number of children infected with TB during 1-2 year. To prevent infant
      TB, reinforcement of contact surveys to identify LTBI for treatment, improvement
      of BCG coverage, and attention to BCG non-vaccinated infants older than 6 months
      might be effective.

PMID- 21174735
TI  - [Discharge decisions for pulmonary tuberculosis patients].
AB  - PURPOSE: To understand how decisions to discharge pulmonary tuberculosis patients
      were made at our hospital. SUBJECTS: 28 pulmonary tuberculosis patients admitted
      based on the criteria of the Ministry of Health, Labor and Welfare between
      January 23 and July 22, 2009 who received standard chemotherapy according to the
      "Tuberculosis Treatment Standards." Discharge decisions were made using the
      criteria of the Ministry of Health, Labor and Welfare. METHODS: The patients were
      divided into 2 groups: a culture group in which the criterion of "3 consecutive
      negative cultures" was used as the criterion for deciding discharge, and a smear
      group in which "3 consecutive negative smears" was used as the criterion for
      deciding discharge. Patients' attributes, clinical findings, and treatment course
      were compared retrospectively between the 2 groups. RESULTS: Significant
      differences were seen between the groups in age, performance status, treatment
      method (4-drug, 3-drug), temporary discontinuation of chemotherapy, need for
      hospitalization or admission to a care facility for the purpose of convalescence
      after discharge, and number of days from admission until the criteria for
      discharge were met. CONCLUSION: Compared to patients in the smear group, those in
      the culture group tended to be older and in poorer general condition, more
      frequently needed further hospitalization or admission to a facility for the
      purpose of convalescence after discharge and required a longer time from
      admission until the criteria for discharge were met.

PMID- 21174736
TI  - [Examination of latent tuberculosis infection treatment status].
AB  - OBJECTIVE: To clarify factors involved in the refusal or discontinuation of
      treatment for latent tuberculosis infection (LTBI), we reviewed LTBI treatment.
      METHOD: The subjects were 193 patients for whom LTBI treatment was indicated on a
      family contact investigation in 2006. We examined the subjects' backgrounds and
      reasons for treatment refusal or discontinuation. In addition, we investigated
      the incidence of the onset of tuberculosis within 2 years after the final contact
      with the source of infection. RESULTS: i) Patient background: The state of
      treatment could be evaluated in 185 patients. Of these, drug therapy was
      completed in 138 (75%), whereas 47 (25%) refused or discontinued treatment. The
      mean ages of the former and latter were 21.0 and 26.2 years, respectively,
      showing a significant difference. Concerning the state of contact, 9 (8%) of 114
      patients who had lived with and 12 (17%) of 71 who had lived apart from the
      source of infection refused treatment, showing a significant difference. ii)
      Onset within 2 years: We analyzed 180 patients for whom follow-up was possible.
      Drug therapy was completed in 137 patients. No patient developed tuberculosis
      onset. On the other hand, drug therapy was not completed in 43 patients, and 6
      (14%) developed tuberculosis onset. iii) The reasons were investigated in 47
      patients who did not complete drug therapy. There were 15 episodes associated
      with side effects, followed by 14 related to personal circumstances, such as
      being busy, disliking medicines, and the absence of confidence regarding the
      completion of drug therapy, and 6 associated with either insufficient
      explanations regarding the diagnosis or an absence of symptoms. CONCLUSION:
      Treatment refusal/discontinuation was more frequent in the more advanced age
      groups and patients who had lived apart from the source of infection. It may
      therefore be necessary to more closely explain the importance of treatment to
      these patients. Most reasons for treatment refusal/discontinuation were
      associated with side effects or insufficient explanations, suggesting the
      necessity of providing sufficient information to aid in patient understanding.

PMID- 21174737
TI  - [Mass health examination for tuberculosis].
AB  - Miniature radiography or radiophotography (RP) was first developed independently
      by de Abreu M of Brazil and Koga Y of Japan in 1936, and because of its utility,
      it was used as a tool of mass health examination for TB all over the world soon
      after its development. The idea of RP is to take a picture of the chest X-ray
      image on a fluorescent screen set in a dark box, and this idea was materialized
      through development of a camera with a small F-number. Through application of RP
      as a tool for mass health examination, many TB cases had been detected, and most
      of these had been previously unknown cases. In the TB Control Law legislated in
      1951, the three major components were (1) early detection of TB cases by mass
      miniature radiography (MMR), (2) prevention of TB by BCG vaccination, and (3)
      distribution of adequate TB treatment. MMR first covered the population below 30
      years of age, as it was thought that the prevalence of TB was high among young
      adults. However, based on the results of the TB Prevalence Survey in 1953, it was
      expanded to the whole population in 1955, and since 1957, all MMR, tuberculin
      skin tests, and BCG vaccinations have been carried out free of charge for
      community residents in Japan. The expenses are shared, in equal thirds, by the
      central government, the prefectural government, and the community office. The
      numbers of persons examined by MMR are shown in Fig. 1, and the detection rate of
      TB cases by MMR and other health examinations are shown in Fig. 2. In accordance
      with the decline in TB, the number of MMR subjects has gradually been reduced,
      starting with primary and junior high school students and then with senior high
      school students, to a point where cases are now confined to those 65 years of age
      and above and inhabitants living in TB high-incidence areas. The most marked
      outcomes had been obtained in big enterprises, in which twice yearly MMR had been
      carried out. These efforts had resulted in a significant rapid decline in cases
      of TB requiring absence from work as shown in Fig. 3. As sick leave and cost for
      medical care were secured for 3 years for TB cases in big enterprises in Japan,
      this rapid decline contributed to the rise of productivity of big enterprises and
      ultimately to rapid growth of the GNP of Japan. In big enterprises in Japan, in
      contrast to the rapid decline of TB, the incidence of cancer and other lifestyle
      related diseases had increased, and annual examinations for new diseases were
      introduced as a control measure without thorough analysis of the effectiveness of
      these examinations. In the case of MMR for TB, before its use as a control
      measure, procedures including detailed examinations and post-examination
      management were fully tested, and outcomes were evaluated, and such procedures
      were needed for health examinations for cancer and other lifestyle-related
      diseases. The contribution of MMR to the rapid decline of TB in Japan has been
      highly evaluated, however, success of MMR has resulted in the decline of
      detection rate of TB, thus deteriorate the cost-effectiveness of MMR. Timing of
      reducing its use has not been sufficiently examined, and it might be done a
      little bit earlier.

PMID- 21174738
TI  - [Disease progression of Mycobacterium avium pulmonary infection and the
      mycobacterial variable number tandem repeat (VNTR) typing].
AB  - The disease progression of nontuberculous mycobacterial (NTM) pulmonary infection
      is variable, and it is sometimes difficult to distinguish between patients who
      require immediate therapy and those in whom such a decision can be withheld. Here
      we show that the progression of NTM lung disease due to Mycobacterium avium
      infection is significantly associated with the mycobacterial genotype. This
      suggests that genotyping of M. avium isolates may enable us to predict whether
      the lung disease will progress or not.

PMID- 21174739
TI  - [Prospects for the development of new antituberculous drugs putting our hopes on
      new drug targets].
AB  - Worldwide, tuberculosis remains the most frequent and important infectious
      disease to cause morbidity and death. However, the development of new drugs for
      the treatment and prophylaxis of TB has been slow. Therefore, novel types of
      antituberculous drugs, which act on the unique drug targets in Mycobacterium
      tuberculosis, particularly the drug targets related to the establishment of
      mycobacterial dormancy in host's macrophages, are urgently needed. In this
      context, it should be noted that current antituberculous drugs mostly target the
      metabolic reactions and proteins which are essential for the growth of M.
      tuberculosis in extracellular milieus. It may also be promising to develop
      another type of drug that exerts an inhibitory action against bacterial virulence
      factors which cross talk and interfere with signaling pathways of M. tuberculosis
      infected host immunocompetent cells such as lymphocytes, macrophages and NK
      cells, thereby changing the intracellular milieus favorable to intramacrophage
      survival and growth of infected bacilli. In this review article, I will describe
      recent approaches to identify and establish novel potential drug targets in M.
      tuberculosis, especially those related to mycobacterial virulence, dormancy, and
      cross-talk with cellular signaling pathways.

PMID- 21174740
TI  - [Biomarkers to assess different aspects of tuberculosis--from development to
      relapse].
AB  - Prevalence of tuberculosis (TB) has been decreased in Japan, whereas rapid
      increases in multi-drug resistance TB and HIV co-infection have raised serious
      problems in developing countries. To solve these problems, development of strong
      anti-TB vaccine, simple low-cost tools for diagnosis with drug sensitivity
      testing and new powerful anti-TB drugs is in urgent need. To evaluate new weapons
      against TB properly, appropriate biomarkers to assess the presence and severity
      of disease, response to treatment and prediction of relapse should be
      established. In case of TB, no relapse within two years after treatment is a gold
      standard to evaluate treatment outcome, but if we have a surrogate biomarker to
      predict relapse more quickly and accurately, clinical trials for TB drugs will be
      facilitated. A candidate TB vaccine may also be evaluated in a similar way. It
      may be further useful for individualized medicine to determine optimal dose and
      duration of TB treatment for each patient. I will review the current situation of
      biomarker studies and a new trend for development of biomarkers based on
      platforms of "omics" technology.

PMID- 21174741
TI  - [Adenocarcinoma of the rete testis. A case report].
AB  - Adenocarcinoma of the rete testis is a rare malignant tumor with a poor
      prognosis. About 60 cases of this adenocarcinoma have been reported in the
      literature. The diagnosis is often difficult and made incidentally. Herein, we
      report a case of adenocarcinoma of the rete testis and review the literature. Our
      patient was an 80-year-old man who presented with painless scrotal swelling for 2
      years. Physical examination revealed an enlarged, hard mass of the left scrotum.
      The serum markers alpha-fetoprotein (AFP), beta-human chorionic gonadotropin
      (beta-HCG), and carcinoembryonic antigen (CEA) were negative. Magnetic resonance
      imaging (MRI) showed a left hydrocele with central necrosis of the testis. After
      4 months, the patient presented with appetite loss, general fatigue, and pain in
      the left scrotum. Positron emission tomography (PET) was performed in another
      hospital, and the patient was referred for a left testicular tumor, multiple lung
      metastases, and para-aorta lymph node metastasis. The patient underwent left high
      inguinal orchiectomy. Pathological examination revealed a hard whitish mass
      around the testis involving the epididymis and tunica vaginalis and spreading
      under the subcutaneous tissue. Histological examination revealed adenocarcinoma
      in the hilum of the testis, which extended to the subcutaneous tissue but not to
      the surface of the scrotum. The tunica albuginea was intact, and no invasion of
      carcinoma in the testis was seen. After the histological diagnosis of
      adenocarcinoma of the rete testis was confirmed, computed tomography (CT) was
      performed and showed multiple pulmonary nodules and para-aortica lymph node
      swelling of 3 cm diameter. Because the patient did not wish to receive
      chemotherapy or other aggressive treatment, he has been followed-up with
      palliative care since his diagnosis. Although local recurrence has occurred 4
      months later, he is still alive for 8 months since his diagnosis.

PMID- 21174742
TI  - [Holmium laser enucleation of the prostate (HoLEP) in patients with continuous
      oral anticoagulation: first reported cases in Japan].
AB  - Oral anticoagulation (OA) has been considered as a strict contraindication to
      transurethral resection of the prostate (TURP). In recent years, some studies
      have shown that holmium laser enucleation of the prostate (HoLEP) has less blood
      loss compared to TURP. Thus we have performed HoLEP in patients with benign
      prostatic hyperplasia (BPH) under continuous OA from September 2009, and herein
      we report our first nine cases. Patients received HoLEP by a single surgeon at
      our institution. HoLEP was performed successfully in all patients. The mean times
      to complete enucleation and morcellation were 48.2 and 5.1 minutes, respectively.
      The mean tissue weight of enucleation was 37 grams. The mean hemoglobin and
      sodium loss after HoLEP were 1.7 g/dl and 1.3 mEq/L, respectively, and the
      catheterization time was 1.6 days. Blood transfusion, clot retention or
      transurethral resection syndrome were not observed in any cases. HoLEP has
      excellent hemostatic properties, and is a safe and effective procedure for
      patients with symptomatic BPH under the condition of continuous OA.

PMID- 21174743
TI  - [Successful long-term management of hepatic and lymph nodes metastases of
      ureteral cancer by multimodal treatment including radiofrequency ablation].
AB  - A 56-year-old man presented with asymptomatic gross hematuria. Computed
      tomography (CT) scan revealed right hydronephrosis and a slightly enhanced
      invasive tumor in the right lower ureter, providing a diagnosis of ureteral
      cancer stage cT3NOM0. The patient underwent minimum incision endoscopic
      nephrouretectomy, and pathological examination of the resected specimen revealed
      urothelial carcinoma and squamous cell carcinoma with metastases to right
      obturator lymph nodes (pT3pN2). Ten months later, CT scan of the abdomen revealed
      two hepatic metastases. After three courses of combination chemotherapy
      consisting of gemcitabine and cisplatin (GC), one tumor completely disappeared
      and another achieved a partial response. The patient underwent radiofrequency
      ablation (RFA) for the residual followed by GC chemotherapy. However, eighteen
      months later, CT scan of the abdomen revealed two metastatic foci in other
      hepatic lesion. The patient underwent RFA again followed by GC chemotherapy and
      then all hepatic metastases have not revealed enlargement. More than three years
      after surgery, the patient has achieved a high quality of life.

PMID- 21174744
TI  - [Application of vestibular autorotation test in diagnosis of benign paroxysmal
      positional vertigo].
AB  - OBJECTIVE: The objective of this study was to evaluate the utility of vestibular
      autorotation test in the diagnosis of BPPV. METHOD: VAT and caloric test were
      performed on 41 patients with BPPV. VAT results were analyzed according to the
      affected semicircular canal. RESULT: Results of VAT were abnormal in 34 (82.93%)
      patients with BPPV. Fourteen cases were found with abnormal vertical phase, 1
      case with abnormal vertical gain in a total of 21 vertical semicircular canal
      BPPV patients. Six cases with abnormal horizontal phase lead, 5 cases with
      abnormal horizontal gain, 2 cases with asymmetry were found in 12 patients with
      horizontal semicircular canal BPPV. Phase lead was abnormal in all frequencies in
      4 patients, and in 2-3 Hz in 21 patients. 24 (58.54%) patients showed abnormal
      canal paresis (CP) and direction preference (DP) in caloric test. CONCLUSION: VAT
      can indicate information of vestibular function in both vertical and horizontal
      semicircular canal. Phase of VAT is constantly enhanced in BPPV, especially in 2
      3 Hz. As the supplement of caloric test, VAT may prove helpful in assessment of
      semicircular canal function.

PMID- 21174745
TI  - [A systematic review of vasodilators for sudden sensorineural hearing loss].
AB  - OBJECTIVE: To evaluate the efficacy and safety of vasodilators for sudden
      sensorineural hearing loss. METHOD: Based on the principles and methods of
      Cocharne Systematic Reviews, we searched the cochrane central register of
      controlled trials, PubMed, Embase, ISI, the China biological medicine datebase,
      VIP, CNKI and Wangfang database. Randomized controlled trials about using
      vasodilators to treat sudden sensorineural hearing loss were included. Meta
      analysis was performed for the results of homogeneous studies using RevMan
      software. RESULT: Twenty eight randomized control trials met the inclusion
      criteria. Seven studies showed vasodilators was not more effective than placebo.
      From 14 studies comparing vasodilators with vasodilators and 9 studies comparing
      vasodilators with other drugs, no definite conclusion could be drawn. CONCLUSION:
      The evidence currently available does not support the use of vasodilators in the
      treatment of sudden sensorineural hearing loss. Further randomized, double-blind,
      placebo-controlled trials are needed in order to define the efficacy and
      acceptability of vasodilators in the treatment of sudden sensorineural hearing
      loss.

PMID- 21174746
TI  - [An introduction of different positioning tests of benign paroxysmal positional
      vertigo and their clinical values].
AB  - OBJECTIVE: To explore the clinical value of different positioning tests for
      different benign paroxysmal positional vertigo (BPPV). METHOD: This research
      applies Dix-Hallpike test and Side-lying test for PC-BPPV, Roll test and WRW test
      for HC-BPPV, Dix-Hallpike test, Side-lying test and Rahko T maneuvers for SC
      BPPV. Six hundred and thirteen cases, who were tested with different positioning
      tests in the sequence of firstly PC-BPPV then HC-BPPV and finally SC-BPPV, were
      randomly divided into 2 groups. The order of positioning tests for PC-BPPV and HC
      BPPV in the two groups was reversed. RESULT: There's no significant difference
      between the detection rate of Dix-Hallpike test and Side-lying test for PC-BPPV
      (P > 0.05). Similarly, there's no difference in statistics between the detection
      rate of Roll test and WRW test for HC-BPPV (P > 0.05). However, the detection
      rate of Rahko T maneuver was higher than the other two tests for SC-BPPV and the
      differences were statistically significant (P < 0.05). The detection rates of
      different positioning tests for PC-BPPV and HC-BPPV between the two groups were
      not different in statistics (P > 0.05), which implies that the different order
      had no effect on the sensitivity of each positioning test. CONCLUSION: Dix
      Hallpike test is recommended as the first choice for PC-BPPV for its more
      efficient stimulus to the posterior semicircular canal, and Side-lying test is
      recommended as a prior choice to the patients with suspected PC-BPPV but unable
      to receive Dix-Hallpike test because of its similar sensitivity and more
      convenient manipulation. The detection rate of Both Roll test and WRW test were
      higher than 90% and there's no significant difference between the two tests. In
      addition, Roll test is easier to perform and helpful for the therapy, so its
      considered as the preferred test for HC-BPPV with WRW test as the supplement
      test. Nevertheless, for SC-BPPV the sensitivity of Rahko T maneuver was higher
      than that of the other two tests, so it can be used to confirm the suspected SC
      BPPV patients detected or missed diagnosed by the two other tests. To avoid
      misdiagnosis or missed diagnosis, the judgment of affected semicircular canal is
      determined not only by positioning test but also by the feature of nystagmus.

PMID- 21174747
TI  - [Diagnostic function of SLC26A4 hot spot mutations screening to enlarged
      vestibular aqueduct syndrome].
AB  - OBJECTIVE: To investigate the frequencies of SLC26A4 hot spot mutations by
      genetic testing method in non-syndromic hearing loss children. The feasibility of
      genetic screening method in finding enlarged vestibular aqueduct syndrome was
      confirmed by temporal bone CT scan. METHOD: Ninety-two children with moderate
      profound hearing loss were enrolled and DNA were extracted from peripheral blood.
      SLC26A4 IVS7-2A > G and H723R mutations were analyzed by direct sequencing. The
      individual with homozygous, compound heterozygous or heterozygous SLC26A4
      mutations was given further temporal CT scan. RESULT: The sequencing results
      revealed 11 (12.0%) cases carrying SLC26A4 mutations, including 5 cases of bi
      allelic mutation and 6 cases of single allelic mutation. CONCLUSION: The SLC26A4
      mutations has a high carrying rate in non-syndromic hearing loss children. The
      screening for the SLC26A4 gene mutations is useful in the diagnosis of EVAS.

PMID- 21174748
TI  - [Clinical features of 168 patients with vertigo].
AB  - OBJECTIVE: To investigate the clinical characteristics and common etiology of
      vertigo. METHOD: The clinical data of 168 patients with vertigo in the department
      of otolaryngolology and neurology from December 2007 to March 2009 were
      retrospectively analyzed The patients were inquired and examined by pure tone
      average thresholds, videonystagmography, Dix-Hallpike test, cervical spine X-ray,
      skull CT and (or) MRI and transcranial Doppler. RESULT: One hundred and thirty
      four patients with vertigo were of peripheral origin, with 66 cases benign
      paroxysmal positional vertigo, 30 cases Meniere's disease, 24 cases sudden
      deafness, 5 cases vestibular neuritis, 5 cases otitis media ,2 cases ear herpes
      zosters and 2 cases ototoxicity. Among 26 patients with vertigo of central, 20
      patients were vertebrobasilar TIA. CONCLUSION: The most common etiology of the
      vestibular peripheral vertigo is the benign paroxysmal positional vertigo.
      Detailed history and the features of vertigo, particular about the duration of
      vertigo and hearing change, may provide the important evidences for the accurate
      diagnosis and differential diagnosis of vertigo.

PMID- 21174749
TI  - [The analysis of concomitant vertigo in idiopathic sudden deafness].
AB  - OBJECTIVE: Analyzing different types of concomitant vertigo in sudden deafness
      (SD) patients with different hearing loss types, exploring different pathogenesis
      of SD and concomitant vertigo. METHOD: The clinical data of 121 SD cases during
      2007. 12 - 2009. 4 were retrospectively analyzed. Detailed information including
      age, sex, history and hearing level were recorded. According to the standard of
      China Medical Association,all patients were classified into five sub-groups based
      on audiogram types: low frequency SD, high frequency SD, flat frequency SD and
      total SD. The proportion of vertigo in different SD types were calculated and
      analyzed by statistical method. RESULT: Among all 121 cases, 45 cases with
      concomitant vertigo, the proportion in different SD types was 42.9%, 47.1%, 23.6%
      and 51.4%, respectively. By chi-square test, P < 0.05, the proportion in the flat
      type was statistically lower than that of the other types. 23 patients were
      diagnosed as true vertigo. The vertigo incidence in different SD types had no
      statistical difference. CONCLUSION: Vaso factor and viral infection played
      different roles in different SD types. Discussing concomitant vertigo could help
      understand SD and otogenic vertigo.

PMID- 21174750
TI  - [Evaluation of a transient noise reduction strategy on the loudness perception
      and sound quality].
AB  - OBJECTIVE: A current technology for detecting and controlling transient noise in
      hearing aids (AntiShock) was evaluated. The objective was to evaluate AntiShock
      on loudness control and whether results in negative changes in sound quality of
      speech, transient noise and environmental noise and provide implications for
      hearing aid fitting. METHOD: Twenty-four subjects with sensorineural hearing loss
      participated in the study. In a single-blinded paradigm, the subjects were asked
      to rate loudness of transient noise and distortion of speech, transient noise and
      environmental noise with the AntiShock in both on and off conditions. RESULT: (1)
      The percentage of the transient noise rated as soft, comfortable, loud, too loud
      was 3.0%, 72.7%, 22.9% and 1.4%, respectively. There were significant differences
      in mean scores of loudness perception among listening conditions and between
      genders by a Two-Way ANOVA, the P values were 0.009 and 0.001, respectively. (2)
      The percentage of the speech rated as mild distorted, understandable, clear and
      very clear was 2.5%, 30.6%, 32.9% and 34.0%, respectively. There were significant
      differences in mean scores of speech distortion under different listening
      conditions by an One-Way ANOVA (P < 0.01). (3) The percentage of the transient
      noise rated as mild distorted, clear and natural was 2.9% and 97.1%,
      respectively. No significant differences in mean scores of nature of transient
      noise was found under different listening conditions by an One-Way ANOVA (P >
      0.05). (4) The percentage of the environmental noise rated as mild distorted,
      clear but soft, clear and natural was 0.4%, 0.8% and 98.8%, respectively. No
      significant differences in mean scores of nature of environmental noise was found
      between different listening conditions by an Independent-Samples T Test (P >
      0.05). CONCLUSION: AntiShock showed positive effects on the loudness control of
      the transient noise. Quality of speech, transient noise and environmental noise
      were not impacted by AntiShock.

PMID- 21174751
TI  - [The effect of hyperbaric oxygen therapy to different degree of hearing loss and
      types of threshold curve in sudden deafness patients].
AB  - OBJECTIVE: To investigate the effect of hyperbaric oxygen therapy to different
      degrees of hearing loss and different types of threshold curve in sudden deafness
      patients, and establish a personalized therapy, so as to promote clinical effect
      to sudden deafness. METHOD: One hundred and twenty cases were divided into two
      groups respectively (each group 60 cases). Drug treatment had been used in group
      A for two weeks. The patients in group B received drug treatment combined with
      hyperbaric oxygen therapy for two weeks. According to the different degrees of
      hearing loss and the types of audiogram in two groups, the statistical analysis
      to the difference of hyperbaric oxygen therapeutic effect was done. RESULT: The
      effective rates was statistically different (chi2 = 8.044, P < 0.01) between
      group A (60.00%, 36/60) and group B (83.33%, 50/60). There was no statistical
      difference between two treatment program in mild and the profound deafness
      patients. The statistical difference could been found between moderate and the
      severe deafness, the value of chi2 and p were 4.969, 5.560 and 0.040, 0.035,
      respectively. In group A, the statistical difference could only been found
      between mild and the profound deafness patients (chi2 = 6.739, P < 0.05). In
      group B, the statistical difference could been found in mild and the profound
      deafness, the moderate and the profound deafness, the severe and the profound
      deafness patients. The value of chi2 were 11.500, 15.058,10.221 and P < 0.01
      respectively. The effective rates was no statistical difference in two treatment
      programs in the upsloping audiogram and the profound deafness. The statistical
      difference could been found between the downsloping and the flat audiogram, with
      the value of chi2 and p were 5.144 and 5.969, P < 0.05, respectively. In group A,
      the statistical difference could been found between the ascending and descending
      audiogram, the ascending and the flat audiogram,the ascending type and the
      profound deafness. The value of chi2 were 6.188, 7.247, 8.082 and P < 0.05,
      respectively. No statistical difference could been found among the other types of
      audiogram. In group B, no statistical difference could been found among all types
      of audiogram. CONCLUSION: The effect of hyperbaric oxygen therapy varies with
      degree of hearing loss and audiogram type. Drug treatment combined with HBOT can
      promote clinical effect for patients in moderate deafness and severe deafness,
      the descending and flat type of audiogram.

PMID- 21174752
TI  - [The study of the high sensitivity to noise trauma in the inner ear mimetic aging
      model].
AB  - OBJECTIVE: Use the inner ear mimetic aging model which has been established by
      our research institute, investigate its sensitivity to noise trauma and the
      possible role of mitochondrial DNA deletions. METHOD: Thirty-two Wistar rats of 2
      months old were randomly divided into four groups. In group A, D-galactose was
      subcutaneously injected at dose of 150 mg/kg weigh per day for 8 weeks, after
      that these rats were exposed to 110 dB SPL noise 4 hours each day, for 2 days.
      Group B were given normal saline (NS) injected at dose of 150 mg/kg weigh per day
      for 8 weeks,also given noise exposure as that of group A. Group C were give D
      galactose without noise exposure. Group D were given normal saline (NS) without
      noise exposure. The thresholds of auditory brainstem response (ABR) were measured
      2 weeks after stopping of noise exposure. And T-SOD and MDA of the inner
      membranous labyrinthine tissue were measured. Nest polymerase chain reaction
      (Nest PCR) were used to identify the mtDNA common deletion (CD), and PCR products
      were sequenced in the meantime. RESULT: The elevation of the mean ABR thresholds
      in group A was higher than that in group B, and the difference had statistic
      significance (P < 0.01). The reduction of T-SOD in group A was obvious, while the
      level of MDA was greatly increased. The difference in the levels of T-SOD and MDA
      between group A and group B had statistic significance (P < 0.01). The detection
      rate of mtDNA 4834 deletion were as follows: group A 87.5% (7/8); group B 12.5%
      (1/8); group C 75.0% (1/8); group D 0(0/8). CONCLUSION: The rat in the inner ear
      mimetic aging model are hypersensitive to noise exposure, and mtDNA4834 deletions
      in the inner ear may play an important role in it.

PMID- 21174753
TI  - [Aflatoxin contamination of Chinese herbal medicine in China and its potential
      management strategies].
AB  - The mould phenomenon occurred commonly in the cultivation, processing and storage
      period of medicinal materials, which may result in production of mycotoxins.
      Mycotoxin contaminations caused by fungi are major issues related to the quality
      and safety of Chinese herbal medicine. This review summarized the work published
      in aflatoxins contamination of Chinese herbal medicine in China through the
      previous decade. The conclusion to be drawn from this survey is that aflatoxin
      exposure remains an important aspect of Chinese herbal medicine safety which
      needs to be paid great attention. We raised some points that should be focused on
      in future. The strategies of changing environment to suppress growth of toxin
      producing fungus, so as to reduce aflatoxins are the most practical and effective
      ways, while biological control in the field production is a promising approach.

PMID- 21174754
TI  - [Determination of 25(R, S) ruscogenin 1-O-[beta-D-glucopyranosyl (1 --> 2)] [beta
      D-xylopyranosyl (1 --> 3)] beta-D-fucopyranoside in Liriope muscari from
      different habitats and different harvest time by HPLC-ELSD].
AB  - OBJECTIVE: To develop an HPLC-ELSD method for the determination of 25 (R, S)
      ruscogenin 1-O-[beta-D-glucopyranosyl (1 --> 2)] [beta-D-xylopyranosyl (1 --> 3)]
      beta-D-fucopyranoside in the tuberous roots of Liriope muscari from different
      habitats and different harvest time. METHOD: A Shimadzu C18 column (4.6 mm x 150
      mm, 5 microm) with a solvent system consisting of acetonirile-water (46: 54) was
      used, and detected by ELSD. The temperature of drift tube was 94 degrees C and
      the nebulizer nitrogen flow rate was 2.5 L x min(-1). RESULT: The calibration
      curve of 25 (R, S) ruscogenin 1-O-[beta-D-glucopyranosyl (1 --> 2)] [beta-D
      xylopyranosyl (1 --> 3)] beta-D-fucopyranoside showed good linearity in the range
      of 1.02-12.228 microg and the average recovery was 100.80%, with RSD of 1.8%. 10
      batches of L. muscari from different habitats were analyzed, and the contents
      were 0.25% - 0.41%. The contents of 15 batches from different harvest time were
      0.13%-0.38%. CONCLUSION: The method is simple, rapid and sensitive, and can be
      used for determination of 25 (R, S) ruscogenin 1-O-[beta-D-glucopyranosyl (1 -->
      2)] [beta-D-xylopyranosyl (1 --> 3)] beta-D-fucopyranoside in L. muscari. It
      provides the valuable basis for quality assessment of L. muscari.

PMID- 21174755
TI  - [Analysis of dynamic change of huperzine A content in Huperzia serrata].
AB  - A precise and selective reversed phase high-performance liquid chromatographic
      method (HPLC) was used to quantify the levels of huperzine A in samples of three
      Huperzia serrata populations with a total of 73 individuals located in Zhejiang,
      Guangxi, Chongqing, respectively, as well as in one-to-one samples of these 73
      individuals introduced in same site after one year. Huperzine A content variation
      both among and within populations, and the dynamic change of this alkaloid
      occurring in same population after one year introduction, were analyzed using
      SPSS 13.0 software (Coefficient of variation, One-way ANOVA analysis, Paired
      samples T tests). The results indicated that huperzine A content varied
      significantly by geographical locations, especially change with longitude, i. e.,
      the order of the huperzine A content was CQ population > GX population > ZJ
      population. The coefficients of variation (CV) were as follows: 0.36 (CQ), 0.44
      (GX) and 0.40 (ZJ). This indicated that there was plentiful diversity concerned
      with huperzine A content among individuals within population. Moreover, this high
      diversity was still maintained after one year introduction. ANOVA analysis showed
      that there was significant difference among populations in huperzine A content.
      Finally, the significant change of huperzine A content was not observed in all
      three populations after one year introduction. The results presented in this
      study could provide evidence that the huperzine A content variation of H. serrata
      is the results of an interaction between genes and the environment, by
      comparison, is mainly controlled by genetic factor.

PMID- 21174756
TI  - [Breeding and spreading of new vairety "Yu-Qing No. 1" of Artemisia annua].
AB  - OBJECTIVE: To breed and spread a new cultivar of Artemisia annua. METHOD: The
      excellent germplasm resources of A. annua in the main production area of
      Artemisia were collected, and the improved germplasm were screened, the content
      of artemisinin was determined, and yield per plant was measured. The
      systematically maternal line and seed production techniques of mass selection
      were applied combined with the variety test, variety regional test trials and
      production trials for breeding and spreading the new cultivars of artemisia.
      RESULT: The popularization and experiment illustrated the production of the new
      species reached 3 000 kg x hm(-2), compared with wild A. annua it increased 10% 
      14%. The content of artemisinin reached more than 1%, increased more than 0.2%.
      CONCLUSION: It is proved that the systematically maternal line and seed
      production techniques of mass selection can significantly improve the quality of
      A. annua and it is an acceptable way to cultivate new variety. By production
      verification, it is practicable and high technical and economic benefits to
      popularize the new cultivar "Yu-Qing No. 1" of A. annua.

PMID- 21174757
TI  - [Comparison on pollen morphology among populations of Changium smyrnioides].
AB  - OBJECTIVE: To observe the pollen morphological differences among different
      populations of Changium smyrnioides. METHOD: The pollen morphology of 10
      populations were examined through LM and SEM observations. RESULT: Pollens in
      different populations were distinguished from each other in the size, the largest
      average size was the pollen of the population cultivated in Hongshan, and the
      smallest was that of the population cultivated in Jiuhuashan. Pollens were oval
      shaped in all of the populations, and P/E values were around 1.5. Typical feature
      of surface ornamentation was stripe-like structure, different populations were
      distinguished from each other in the texture depth and the gap. With different
      length and width in different populations, typical feature of germinal aperture
      was nearly square and 3 germinal furrows. Variation with 4 germinal apertures
      were found in the pollen of population cultivated in Hongshan. CONCLUSION:
      Diversity of pollen morphology was high, and differentiation was strong in Ch.
      smyrnioides.

PMID- 21174758
TI  - [DNA barcoding in medicinal plants Caprifoliaceae].
AB  - OBJECTIVE: To determine the candidate sequences which can be used as DNA barcode
      to identify species in Caprifoliaceae family by screening out from four different
      DNA fragments sequences. METHOD: PCR amplification, sequencing efficiency,
      differential intra- and interspecific divergences, the DNA barcoding gap and
      identification efficiency were used to evaluate these loci. RESULT: The ITS2 was
      used as a candidate sequence of DNA barcode to identify the species in
      Caprifoliaceae family, whose rate of success in identification in genera level
      was 100% and in species 96.6%, and psbA-trnH as a complementary barcode to ITS2
      for Caprifoliaceae.

PMID- 21174759
TI  - [Comparative research on pharmacognostic characteristics and microscopic
      characteristics of Radix Paeoniae Rubra from different areas].
AB  - OBJECTIVE: To compare pharmacognostic characteristics and microscopic
      characteristics of Radix Paeoniae Rubra (chishao) from different areas. METHOD:
      Pharmacognostic characteristics and microscopic characteristics of Radix Paeoniae
      Rubra were compared by microscope count methods. RESULT: Chishao in duolun was
      more straighter and longer, cortex with a set of closely spaced rill, peel off
      easily, pink section, etc. The wild chishao were different from the cultivated
      chishao on pharmacognostic characteristics and microscopic characteristics, such
      as appearance shape, smell, vessel arrangement, and number of crystal and starch
      in unit area. CONCLUSION: Chishao in duolun were different form others,
      appearance shape, wood fiber, difference of appearance shape, vessel arrangement,
      and number of crystal and starch in unit area can be used as identificatin
      feature of the wild chishao and the cultivated chishao.

PMID- 21174760
TI  - [Effects of gathering season and three age affect on main active components of
      Taxus madia].
AB  - OBJECTIVE: To reveal the influence of harvest season and tree age on the content
      of taxol and 10-DAB III, and provide the basis for the harvest time of Taxus
      madia. METHOD: Branches and leaves of the labeled 25 three-year-old plants and 25
      five-year-old plants were collected every two months from March 26,2009 to
      January 26, 2010. Taxol and 10-DAB III content of different age and growth season
      of Taxus in branches were determined by HPLC. RESULT: Taxol and 10-DAB III
      content were significantly different in different harvesting age. The content of
      five-year-old plants was significantly higher than that of three-year-old plants.
      Taxol and 10-DAB III contents were significantly different in different
      harvesting season, and the highest content of taxol and 10-DAB III was 0.56, 0.32
      mg x g(-1), respectively, in May. CONCLUSION: The May is the suitable harvest
      season for T. madia, but the suitable harvest age need further study which
      according to the main active component and biomass accumulation.

PMID- 21174761
TI  - [Simultaneous determination of ginsenosides and epimedium flavonoids in rat urine
      by HPLC-UV-ELSD].
AB  - OBJECTIVE: To develop and validate a HPLC-UV-ELSD method for the simultaneous
      determination of ginsenosides and epimedium flavonoids in rat urine after
      intravenous administration of Jiweiling freeze-dried powder. METHOD:
      Chromatographic separation was performed on a C18 HPLC column, with gradient
      elution of acetonitrile and water as mobile phase. An UV detector was used at
      detection wavelength of 220 nm. An evaporative light scattering detector (ELSD)
      was used at drift tube temperature of 80 degrees C and gas pressure of 172.4 kPa.
      RESULT: The calibration curves were linear over the investigated concentration
      ranges with all correlation coefficients higher than 0.998. The a intra- and
      inter-day RSD were less than 9.1% and the relative errors were verage extraction
      recoveries for all compounds were between 88.67% and 101.2%. The within the range
      of -11.58% to 10.89%. CONCLUSION: The proposed method showed appropriate accuracy
      and selectivity and was successfully applied to the rat urine samples analysis of
      saponins and flavonoids after intravenous administration of Jiweiling freeze
      dried powder, which may provide some references to the apprehension of the action
      mechanism and clinical application.

PMID- 21174762
TI  - [Preparation and characterization of non-ionic surfactant vesicle of
      cantharidin].
AB  - OBJECTIVE: To study the preparation of cantharidin entrapped non-ionic surfactant
      vesicle (noisome)and evaluate its quality. METHOD: The niosome loaded with
      cantharidin was prepared using injection method by non-ionic surfactants as the
      carrier. An centrifugation separation method and HPLC analysis method of the
      cantharidin were established to detect the entrapment efficiency. The optimum
      preparation technology was established by a orthogonal experiment. The
      morphology, and particle size were studied to evaluate the preparation. RESULT:
      The average size of niosomes were (209. 8 +/- 0.5) nm. The entrapment efficiency
      of the CTD-NS was (27.5% +/- 2.0%) and Zeta potential was (41.5 +/- 0.65) mV.
      CONCLUSION: The preparation of cantharidin noisome by TweenA and SpanB is
      practicable and successful. These experiments can be the basement of developing
      targeting drug delivery system.

PMID- 21174763
TI  - [United Plackett-Burman and Box-Behnken design to control formation of indirubin
      in process of preparing indigo naturalis].
AB  - OBJECTIVE: To screen the factors that affect indirubin-generated significantly in
      the process of preparing indigo naturalis, optimize level combination and
      determine the optimum technology for indirubin-generated. METHOD: Using
      concentration of indirubin (mg x g(-1)) that generated by fresh leaf as an index,
      Plackett-Burman design, Box-Behnken design response surface analysis as the
      statistical method, we screened the significantly influencing factors and the
      optimal level combination. RESULT: The soaking and making indirubin process in
      preparing indigo naturalis was identified as the wax is not removed before
      immersion with immersion pH 7, solvent volume-leaf weight (mL: g)15, soaked not
      avoided light, soaking 48 h, temperature 60 degrees C, ventilation time of 180
      min, and added ammonia water to adjust pH to 10.5. CONCLUSION: The soaking and
      making indirubin process in preparing indigo naturalis is optimized
      systematically. It clarify the various factors on the impact of the active
      ingredient indirubin which controlled by industrialized production become reality
      in the process of preparing indigo naturalis, at the same time, it lay the
      foundation for processing principle of indigo naturalis.

PMID- 21174764
TI  - [End point determination by HPLC chromatographic fingerprint in processing
      prepared Rehmannia].
AB  - To establish HPLC chromatographic fingerprints to control the quality of Chinese
      herbal medicine. In this study, fingerprints were established based on HPLC-DAD
      chromatographs. And with these fingerprints, content variations of three
      important active components catalpol, 5-hydroxymethylfurfural and acteoside in
      Rehmannia rhizome were analyzed during processing, as well as changes of the
      fingerprints. Fingerprints comparing with the standard prepared Rehmannia
      fingerprints which came from the mean of prepared ones randomly chosen for
      standard was done to seek optimal processing time. The results indicated that
      catalpol decreased quickly as braising prolonged and almost vanished in the end.
      While the active component of 5-HMF increased linearly throughout the process of
      braising. And the content of acteoside did not show obvious change. Similarity to
      standard prepared Rehmannia reached summit after braising for 26 hours. So 26
      hours could be considered to be the optimum time for braising prepared Rehmannia.
      Chromatographic fingerprint is convenient for revealing changes of constituents
      and for accurately controlling quality during processing prepared Rahmannia.

PMID- 21174765
TI  - [Research on X-ray diffraction fingerprints of crude and processed pyritum].
AB  - OBJECTIVE: To establish the X-ray diffraction fingerprints of crude and processed
      pyritum. METHOD: X-ray diffraction fingerprint was used to analyze the crude and
      processed pyritum of different habitat and batch. RESULT: The crude pyritum has
      19 common peaks, while the processed ones has 11. CONCLUSION: The X-ray
      diffraction can express characteristic of the crude and processed pyritum, which
      is specificity, accuracy and reliability and can be used for the quality control
      of crude and processed pyritum.

PMID- 21174766
TI  - [Determination of aromadendrin in Euonymus alatus by HPLC].
AB  - OBJECTIVE: To establish a HPLC method to determine the content of aromadendrin in
      Euonymus alatus. METHOD: Kromasil 100-5C18 column was used with a mobile phase
      composed of acetonitrile-0.3% glacial acetic acid (24:76) at a flow rate of 1.0
      mL x min(-1). The detection wavelength was 292 nm and the temperature of column
      was 30 degrees C. RESULT: The calibration curve was linear in the range of 0.051
      2.04 microg for aromadendrin. The correlation coefficient of the calibration
      curve was 0.999 9. Twenty batches of the crude E. alatus purchased from different
      areas were determined and the contents of aromadendrin in the twigs of E. alatus
      were fluctuated from 0.001 57% to 0.041 6%. CONCLUSION: This method is simple,
      repeatable and can be used for determination of aromadendrin.

PMID- 21174767
TI  - [Alkaloids from Senecio scandens].
AB  - OBJECTIVE: To investigate the alkaloids from Senecio scandens. METHOD: Compounds
      were isolated with silica gel and Sephadex LH-20 column chromatography and their
      structures were determined by spectral analysis and chemical evidence. The
      hepatic cytotoxicity of isolated compounds was tested by MTT method in vitro.
      RESULT: Six alkaloids were obtained and identified as adonifoline (1), 7
      angeloylturneforcidine (2), hordenine (3), 1, 3, 6, 6-tetramethyl-5, 6, 7, 8
      tetrahydro-isoquinolin-8-one (4), 4-(pyrrolidin-2-one) -phenyl acetic acid (5),
      (4-pyrrolidinophenyl) acetic acid (6). CONCLUSION: Compound 6 is a new natural
      product, compounds 3, 4 were obtained from the genus Senecio for the first time,
      compounds 2, 5 were obtained from this plant for the first time. Compound 1
      showed significant growth inhibitory effect against hepatocyte at 100 micromol x
      L(-1).

PMID- 21174768
TI  - [Simultaneous determination of six alkaloids in Coptis chinensis of different
      regions by RP-HPLC].
AB  - A reversed-phase HPLC method for simultaneous determination of gatrorrhizine,
      columbamine, epiberberine, coptisine, palmatine and berberine in Coptis chinensis
      was developed. Analysis was carried out on an Xtimate C18 column (4.6 mm x 250
      mm, 5 microm) eluted with acetonitrile-30 mmol x L(-1) ammonium bicarbonate
      solution (including 0.7% ammonia and 0.1% triethylamine) by gradient elution. The
      detective wavelength was 270 nm, the column temperature was 30 degrees C, and the
      flow rate was 1.0 mL x min(-1). By the above method, the linear ranges of
      gatrorrhizine, columbamine, epiberberine, coptisine, palmatine and berberine were
      0.85-16.96 (r = 0.9997), 1.25-24.96 (r = 0.999 5), 2.05-40.96 (r = 0.999 9), 3.65
      72.96 (r = 0.999 9), 2.88-57.60 (r = 0. 999 8),13.25-264.96 mg x L(-1) (r = 0.999
      6), respectively. The average recoveries (n = 6) of the six alkaloids were 101.6%
      (RSD 1.3%),102.5% (RSD 1.5%), 100.8% (RSD 1.9%),102. 6% (RSD 1.2%), 97.80% (RSD
      1.3%), 99.01% (RSD 1.5%), respectively. The determined results demonstrate that
      there is a significant difference in the contents of six alkaloids and total
      alkaloids among the tested samples. The method is accurate, reliable and
      repeatable for simultaneous determination of gatrorrhizine, columbamine,
      epiberberine, coptisine, palmatine and berberine in C. chinensis.

PMID- 21174769
TI  - [Quantitative analysis of five components in the rhizome of Angelica polymorpha
      by RP-HPLC under different UV wavelengths].
AB  - A HPLC method was developed for simultaneouly quantitative analyses of aviprin
      (1), gosferol (2), 3'R-(+)-hamaudol (3), 3'-O-acetylhamaudol (4) and iso
      imperatorin (5) in the rhizome of Angelica polymorpha. The analysis was performed
      at 25 degrees C on an Agilent Eclipse XDB-C18 analytical column (4.6 mm x 250 mm,
      5 microm) with the mobile phase of methanol and H2O in gradient elution [55:45 (0
      min)-65:35 (25 min)-95:5 (35 min)]. And the flow rate was 1.0 mL min(-1) with the
      detection wavelengths of 312 nm (1), 306 nm (2), 300 nm (3), 294 nm (4) and 310
      nm (5). Consequently, the reqresion equations were Y = 1.81 x 10(3) X + 7.93 x
      10(2) (r = 0.9996), Y = 2.49 x 10(3) X - 2.17 x 10(2) (r = 0.9993), Y = 2.02 x
      10(3) X - 1.42 x 10(2) (r = 0.9991), Y = 1.57 x 10(3) X - 0.66 x 10(2) (r = 0.999
      7), Y = 2.65 x 10(3) X - 1.47 x 10(2) (r = 0.999 6). And the average recoveries
      were 99.7% (RSD 0.57%), 100.1% (RSD 1.3%), 100.0% (RSD 1.6%), 99.6% (RSD 1.3%),
      99.2% (RSD 0.59%), respectively. The precision, repeatability and stability were
      all consistent with the request of quantitative analysis. The contents of
      compound 1-5 in A. polymorpha were determined as 0.525%, 0.044%, 0.046%, 0.043%,
      0.15%, respectively. Accordingly, this quantitative analysis method is good for
      the quality control of A. polymorpha.

PMID- 21174770
TI  - [Metabolites in rat urine after orally administrating gossypetin-8-O-beta-D
      glucuronide].
AB  - OBJECTIVE: To investigate the metabolites in rat urine after orally
      administrating gossypetin-8-O-beta-D-glucuronide. METHOD: Gossypetin-8-O-beta-D
      glucuronide was administrated orally at the dose of 250 mg x kg(-1) to healthy
      rats, then the urine was collected, pre-treated appropriately and detected by
      HPLC-DAD-MS(n). RESULT: In the rat urine, gossypetin-8-O-beta-D-glucuronide,
      along with 6 metabolites, were detected, and their structures were elucidated on
      the basis of reference standards, UV and MS(n) spectra. The metabolic pathways of
      gossypetin-8-O-beta-D-glucuronide included mainly deglycosylation,
      glucuronidation and methylation. CONCLUSION: A rapid and sensitive method for the
      analysis of metabolites in rat urine after orally administrating gossypetin-8-O
      beta-D-glucuronide was established and this will be useful for the further
      metabolism study of gossypetin-8-O-beta-D-glucuronide.

PMID- 21174771
TI  - [Essential oil composition of three herbal medicines from Curcuma wenyujin by GC
      MS].
AB  - OBJECTIVE: To compare the contents and composition of volatile oil of Wenyujin
      (steamed root of Curcuma wenyujin) Wenezhu (steamed rhieome of Curcuma wenyujin)
      and Pianjianghuang (rhizome of Curcuma wenyujin). METHOD: The volatile oils of
      three herbal medicines obtained by steam distillation were determined according
      to the method described in the appendix XD in Chinese pharmacopoeia and
      identified by GC-MS. RESULT: The average contents of volatile oil of Wenyujin,
      Wenezhu and Pianjianghuang were 0.56, 1.99 and 0.94 microL x g(-1), respectively.
      A total of 60 compounds were identified by GC-MS. The amounts of chemical
      components separated and identified in Wenyujin, Wenezhu and Pianjianghuang were
      41, 41 and 40, respectively. Three medicines share a great deal of similarity,
      chemically and genetically. Low boiling point essential oil compositions Wenyujin
      and Wenezhu were similar. While the higher boiling point essential oil
      compositions of Wenyujin and Wenezhu were similar. And the essential oil
      compositions of Wenyujin and Pianjianghuang were distinct. CONCLUSION: Although
      coming from the same origin, the composition of essential oil from different part
      of the plant or various process were discrepant, which lead to rather distinct
      clinical efficacy.

PMID- 21174772
TI  - [Study on effect of total saponins from Semen Nigellae on inflammatory mediators
      and ERK/MAPK pathway in stimulated macrophage].
AB  - OBJECTIVE: To study the anti-inflammatory mechanism of total saponins from Semen
      Nigellae (TSSN). METHOD: IFN-gamma plus LPS stimulated RAW 264. 7 macrophage has
      been used as inflammatory experimental model. Griess reaction for nitric oxide
      production, FRAP assay for total antioxidant capacity, RT-PCR for mRNA expression
      and Western blot for protein expression examination were performed. RESULT: TSSN
      inhibited NO production in a dose-dependent manner. The gene and protein
      expression of iNOS were also suppressed by the herb extract. TSSN treatment
      significantly attenuated mRNA of inflammatory mediators such as COX-2, IL-1beta,
      IL-6 while increased PPAR-gamma gene and protein expression. Furthermore,
      phosphorylation of ERK (p-ERK) was markedly inhibited by TSSN. CONCLUSION: TSSN
      suppressed pro-inflammatory mediators such as COX-2, IL-1beta, IL-6 and increased
      anti-inflammatory mediator PPAR-gamma expression. Meanwhile, TSSN inhibited over
      production of NO and iNOS expression through ERK/MAPK pathway.

PMID- 21174773
TI  - [Influence of separate components of Yiqi Qingwen Jiedu mixture to serum
      inflammatory cytokines of mice infected with influenza virus FM1].
AB  - OBJECTIVE: To observe dynamically the influence of 4 parts of forming of YQJM
      (Yiqi Qingwen Jiedu mixture) (referred to as 4 parts of forming) including the
      methods of relieving superficies with acrid-warm, relieving superficies with
      acrid-cold, clearing away heat and poison and replenishing Qi to serum
      inflammatory cytokines of the model mice infected with influenza virus. And to
      discuss the mechanism of 4 parts of forming of anti-influenza immune injury and
      restoration. METHOD: Made the model with the mice infected by FM1 influenza
      infection, used ELISA method, observed dynamically the influence of four methods
      on the level of serum TNF-alpha, IL-6, IL-1, IFN-gamma and IL-10 inflammatory
      cytokines. RESULT: The level of serum TNF-alpha, IL-6, IL-1 and IFN-gamma of mice
      infected by FM1 significantly increased, while the level of serum IL-10 was lower
      than the control group on the first day of infection, but the levels were much
      higher than the control group in 3 to 7 days after infection. The method of
      relieving superficies with acrid-warm significantly decreased the levels of serum
      TNF-alpha, IL-6, IL-1 on the 5th day after infection, and significantly increased
      the levels of serum IL-10 on the 3rd and 7th day after infection. The method
      could inhibit the immune injury to some extent. The method of relieving
      superficies with acrid-cold decreased the levels of serum TNF-alpha and IL-6 in 5
      to 7 days after infection, increased the level of serum IL-1 on the 3rd day after
      infection, decreased the level of serum IL-1 on the 7th day after infection,
      significantly increased the levels of serum IL-10 in 1 to 3 days and on the 7th
      day after infection. The method could be against inflammatory injury. The method
      of clearing away heat and poison decreased the levels of serum TNF-alpha, IL-6,
      IL-1 after infection in 3 to 5 days and on the 7th day, and significantly
      increased IL-10 each time after infection. It exhibited more strong inhibition of
      inflammatory injury and repair. The method of replenishing Qi significantly
      decreased the level of serum TNF-alpha and IL-6 in 3 to 7 days after infection,
      increased the level of serum IL-1 the first 3 days after infection, but decreased
      the level of serum IL-1 on the 7th day after infection. The method significantly
      increased the levels of serum IL-10 in 3 to 5 days and on the 7th day. It
      exhibited inhibition of inflammatory injury. The method of relieving superficies
      with acrid-cold significantly increased the levels of serum IFN-gamma in 3 days
      after infection, while the methods of clearing away heat and poison and
      replenishing Qi significantly increased the levels of serum IFN-gamma in 1 to 3
      days and on the 7th day. They exhibited anti-virus and suppression of the immune
      injury. CONCLUSION: Chinese medicine could correct the imbalance of inflammatory
      cytokines and be against injury, promote injury restoration, and protect the
      body.

PMID- 21174774
TI  - [Microdialysis and HPLC method for determination of concentration of pantoprazole
      in rat striatum aftercombined administration with borneol].
AB  - OBJECTIVE: To observe the influence of borneol, a traditional Chinese medicine,
      on the concentration of ceftriaxone in the rat brain striatum and evaluate the
      relativity. METHOD: The sample of cerebrospinal fluid in the rat brain striatum
      was collected via brain microdialysis technology, and then the contents of
      ceftriaxone in standard preparation and sample were detected by high efficiency
      liquid chromatography combined with diode array detector respectively and
      analyzed statistically. The concentration of ceftriaxone in rat brain striatum in
      the ceftriaxone + Borneol group was compared with that in the ceftriaxone-only
      group. RESULT: The concentration of ceftriaxone in the rat brain in the
      ceftriaxone + Borneol group (13.01-4.43 mg x L(-1)) is significantly higher than
      that in the ceftriaxone-only group (2.41-0.94 mg x L(-1)). CONCLUSION: Borneol
      can promote ceftriaxone through blood-brain barrier, and increase the
      concentration thereof in striatum.

PMID- 21174775
TI  - [Studies on anti-platelet activation effect and partial mechanisms of Taohong
      Siwu decoction].
AB  - OBJECTIVE: To explore the anti-platelet activation effect and partial mechanisms
      of Taohong Siwu decoction (TSD). METHOD: The effect to venous thrombosis model
      and pulmonary thromboembolism model induced by vein injecting ADP and Adr was
      observed. The platelet adhesion rate was analyzed by using spinning glass bottle,
      and the platelet aggregation rate induced by ADP, Adr was analyzed by using
      turbidimetry. The acute blood stasis rat model was established to analyze the
      content of plasm TXB2 and PGI2 by RIA, and the content of VWF, GMP-14 by ELISA.
      RESULT: TSD could effectively reduce platelet the adhesion rate of normal rat,
      inhibit the platelet aggregation of normal rat induced by ADP, Adr. It
      significantly reduced the plasma TXB2 VWF, and GMP-140 level of blood stasis
      rats. It also had significant tendency to increase 6-keto-PGF1alpha level.
      CONCLUSION: TSD possessed obvious activity of inhibiting platelet activation. The
      mechanism related with the restraining of platelet adhesion, platelet aggregation
      and platelet releasion.

PMID- 21174776
TI  - [Determination of plasma concentration of N-methylcantharidimide by HPLC and its
      pharmacokinetics after intravenous administration in dogs].
AB  - OBJECTIVES: To establish a HPLC method for determination of N
      methylcantharidimide in dogs' plasma and to study the pharmacokinetics of N
      methylcantharidimide in dogs'. METHOD: The plasma samples were extracted by
      methanol. The acetonitrile and the purified water composed mobile phase. The flow
      rate was 0. 7 mL x min(-1), ultraviolet detection wavelength was at 212 nm.
      RESULT: The calibration curve was linear over the range from 0.01-10.0 mg x L(-1)
      with a correlation coefficiency of 0.996 3. The lower limit of quantitation was
      0.01 mg x L(-1). The mean recovery was 92.3%. the relative standard deviation
      (RSD) of intra-day and inter-day were all less than 10%. After intravenous
      administration of N-methylcantharidimide with 3 dosages of 10, 15, 20 mg x kg(-1)
      to dogs, the corresponding distribution half-livers (t1/2alpha) were 1.8, 2.1,
      1.7 min, and the elimination half-lives (t1/2beta) were 144,139, 146 min,
      respectively. CONCLUSION: This method is convenient, accurate and reliable. It
      can be used for determination of N-methylcantharidimide in dogs' plasma and
      pharmacokinetic studies.

PMID- 21174777
TI  - [Rat in vitro plasma-binding percentage determination of sinomenine hydrochloride
      by using microdialysis method and ultrafiltration].
AB  - OBJECTIVE: To assess feasibility of plasma protein-binding percentage by using
      microdialysis method. METHOD: Sinomenine hydrochloride was selected as model
      drug. The in vitro rat plasma protein-binding percentage of three kinds of
      concentration was determinated by using microdialysis sampling tool and HPLC-UV.
      At the same time the classical study method, such as ultrafiltration method, was
      also used to determinate the protein-binding percentage to compare the difference
      between the two methods. RESULT: The in vitro rat plasma protein-binding
      percentage of sinomenine hydrochloride using microdialysis method was about 26%
      and kept relative stable at the concentration range. There was no significant
      difference between the two methods. CONCLUSION: The results shows that the
      binding percentage is relative low. Microdialysis method is a new method for the
      study of protein-binding degree.

PMID- 21174778
TI  - [Study on excretion of stilbene glycoside (THSG) and its beta-cyclodextrin
      inclusion].
AB  - The excretion characteristics of stilbene glycoside (THSG) and its beta
      cyclodextrin inclusion in bile, urine and feces after oral administration to rats
      were studied. Bile for 24 h, urine and feces for 72 h were collected. The content
      of THSG was determined by HPLC-UV. The established HPLC-UV method was available
      for the analysis of THSG in excreta and corresponded to the requirement of
      biological sample analysis. After given THSG and its beta-cyclodextrin inclusion,
      the amount of prototype THSG in feces were 3.27% and 0.61%, meanwhile THSG in
      bile were 0.20% and 0.18%, respectively. Only a little THSG was found in urine.
      The result showed that beta-cyclodextrin inclusion reduced the fecal excretion of
      THSG. However, the characteristic of urinary and biliary excretion wasn't
      changed.

PMID- 21174779
TI  - [Comparative study of effect of Magnolia officinalis and M. officinalis var.
      biloba on gastrointestinal motility dysfunction].
AB  - OBJECTIVE: To compare the effect of Magnolia officinalis and M. officinalis var.
      biloba on gastrointestinal motility dysfunction. METHOD: The gastrointestinal
      motility dysfunction induced by atropine and L-Arg were used in this study. The
      effect of M. officinalis on the gastrointestinal function was evaluated by
      propulsive motility of the total gastrointestinal tract test by recording the
      time of excreting carbo medicinalis, the gastric residualrate, the intestinal
      propulsion rate, the serum levels of D-xylose, motilin (MTL) and gastrin (GAS).
      ED50 were calculated with Bliss's method. RESULT: M. officinalis and M.
      officinalis var. biloba improved the gastrointestinal motility, decreased the
      gastric residual rate, enhanced the intestinal propulsion rate and increased
      serum levels of D-xylose, motilin (MTL) and gastrin(GAS). The ED50 value of M.
      officinalis var. biloba was much higher than that of M. officinalis. CONCLUSION:
      The effect of improving gastrointestinal motility of M. officinalis was proved to
      be superior to that of M. officinalis var. biloba.

PMID- 21174780
TI  - [Enzymatic hydrolysis of antler and properties of hydrolysates].
AB  - Lyophylized antler powder was hydrolyzed by pepsin and trypsin separately and
      also simultaneously to give hydrolysates with special physical activities.
      Complete hydrolysis peptides with MW lower than 1 x 10(3) were collected for
      assay of angiotensin I-converting enzyme (ACE) inhibitory activity, antioxidant
      activity and proliferative activity toward UMR-106 osteoblast cells. The results
      of the experiments revealed that all hydrolysates exhibited potent hydroxyl
      radical scavenging activity with an IC50 value less than 1 mg/ml which was much
      lower than the value of 5.5 g x L(-1) for vitamin C. The peptic and peptic
      tryptic hydrolysates demonstrated strong angiotensin I-converting enzyme (ACE)
      inhibitory activity. The tryptic hydrolysate increased the proliferation of the
      UMR-106 cells by 73.43%. The results verified the traditional use of antler in
      bone-strengthening, anti-aging. The exploratory studies on the ACE inhibitory
      activity of antler hydrolysates indicated that the hydrolysates might be
      potentially useful in prevention and treatment of hypertension. Further
      purification of peptides contributing to the antioxidant activity, angiotensin I
      converting enzyme-inhibitory activity and proliferative activity toward
      osteoblasts from antler hydrolysates is warranted.

PMID- 21174781
TI  - [Application of bioassay in quality control of Chinese materia medica-taking
      Radix Isatidis as an example].
AB  - Bioassay, which construct the characteristics consistents with Chinese medical
      science, is the core mode and methods for the quality control of Chinese materia
      medica. Taking the bioassay of Radix Isatidis as an example, the contribution,
      status and application of bioassay in the quality control of Chinese materia
      medica were introduced in this article, and two key issue (the selection of
      reference and measurement methods) in the process of establishing bioassay were
      also explained. This article expects to provide a reference for the development
      and improvement of the bioassay of Chinese materia medica in a practical
      manipulation level.

PMID- 21174782
TI  - [Reconstruction of phalangeal defect with free mesio-forearm flap based on
      perforator of ulnar artery].
AB  - OBJECTIVE: To discuss the therapeutic effect and clinical experience of a new
      technique of digital reconstruction with the free mesio-forearm flap based on
      perforator of ulnar artery. METHODS: We marked the line from the pisiformis to
      the condylus medialis humeri as the axis of the flap. We used Doppler to detect
      the site of the mesio-forearm ulnar perforator which is usually 9-10 cm proximal
      to the condylus medialis humeri as center of the flap. We designed the flap that
      contained perforator artery with its accompanying vein of the ulnar artery and a
      superficial vein around the center spot along the axis of ulnar artery. The wound
      at donor site was sutured directly. Neurorrhaphy was not conducted in any cases.
      RESULTS: From June 2005 to June 2009, all 12 flaps survived with good quality and
      aesthetic contour. And no necrosis occurred. We conducted 6-36 months follow-up,
      and the result was satisfactory. The function of the fingers was reserved. Two
      point discrimination differed from 6 cm to 12 cm. CONCLUSIONS: The free ulnar
      perforator flap on mesio-forearm can repair digital defect with good therapeutic
      effect, leaving less morbidity at donor site.

PMID- 21174783
TI  - [Application of dorsal pentagonal flap for reconstruction of the web space in
      congenital syndactyly].
AB  - OBJECTIVE: To investigate the therapeutic effect of dorsal pentagonal flap for
      reconstruction of the web space in congenital syndactyly. METHODS: From October
      2007 to August 2009, 10 patients with congenital syndactyly were treated with
      dorsal pentagonal flap for web space reconstruction. During the follow-up period,
      the patients underwent finger functional assessment and web space appearance
      examination. The satisfactory rate of patients was also investigated. RESULTS: 10
      patients with 17 reconstructed web spaces were followed up for 4-25 months
      (median, 15 months). Normal passive flexion and extension of fingers were
      achieved with good cosmetic result at web space. The abduction angle of fingers
      ranged from 30 degrees to 45 degrees. No web creep occurred and no secondary
      procedures were required. All the parents of the patients were satisfied with the
      results. CONCLUSIONS: Web space reconstruction with dorsal pentagonal flap is
      easily performed with reliable blood supply and low re-operated rate. The
      cosmetic and functional result is satisfactory.

PMID- 21174784
TI  - [Clinical application of the distal island muscle flap of the gastrocnemius
      muscle for repairing the defects around knee and within the upper 2/3 of lower
      leg].
AB  - OBJECTIVE: To summarize clinical application of the distal island muscle flap of
      the gastrocnemius muscle for repairing the defects around knee and within the
      upper 2/3 of lower leg. METHODS: 18 patients with defects around knee and within
      the upper 2/3 of lower leg, were treated with the distal island muscle flap of
      the gastrocnemius muscle, including 12 cases with medial muscle head and 6 cases
      with lateral muscle head. The muscular flaps were covered with meshed split
      thickness skin grafts. The wound at donor sites were closed directly. RESULTS:
      All the skin grafts and muscle flaps survived with superior infection at the
      wound edge in two cases. The patients were followed up for 8 months to 4.8 years
      with satisfactory cosmetic and functional results. CONCLUSIONS: The distal island
      muscle flap of the gastrocnemius muscle has a reliable blood supply, long pedicle
      and suitable thickness. It is an ideal method for repairing the defects around
      knee and within the upper 2/3 of lower leg.

PMID- 21174785
TI  - [Relationship between proximal-tip location and partial necrosis in distally
      based sural neuro fasciocutaneous flap: an analysis of 157 flaps].
AB  - OBJECTIVE: To explore the influence of proximal-tip location on partial necrosis
      in distally based sural neuro fasciocutaneous flap. METHODS: From April 2001 to
      May 2009,157 distally based sural neuro fasciocutaneous flaps were conducted to
      repair the soft tissue defect in distal region of lower leg, ankle and feet in
      153 patients. Date of the flaps and the patients were retrospectively analyzed.
      From the tip of lateral malleolus to the popliteal crease, posterior aspect of
      the lower leg was equally divided into 9 regions that were 1st to 9th region from
      inferiorly to superiorly, respectively. The flaps were divided into 2 groups:
      survival group (including uneventfully survived flaps, flaps with distally
      epidermal necrosis and with wound dehiscence) and partial necrosis group. Based
      on the location of the proximal tip of flaps, the flaps were stratified into 4
      groups: flaps with the proximal tip locating in the 6th or lower region (group
      A), the 7th region (group B), the 8th region (group C) and the 9th region (group
      D). Harvesting the flaps started from exploring the perforator of peroneal vessel
      in the adipofascial pedicle, then the flaps were elevated retrogradely. RESULTS:
      Of the 157 flaps, 125 survived uneventfully,8 showed distal epidermal
      necrosis,wound dehiscence occurred in 6 flaps, 18 flaps (11.5%) showed distal
      partial necrosis. Partial necrosis occurred in zero of 19 flaps in group A (0), 1
      of 44 flaps in group B (2.3% ), 7 of 62 flaps in group C (11.3% ) and 10 of 32
      flaps in group D (31.3% ). The differences in partial necrosis rate between group
      A and group B , group B and group C, were not statistically significant (P >
      0.05). Partial necrosis rate was higher in group D than in group C (P = 0.012),
      it was lower in group A + group B (1.6%) than in group C + group D (18. 1% ) (P =
      0. 001). CONCLUSIONS: Distally based sural neuro fasciocutaneous flap can survive
      reliably when the proximal tip of flap is not beyond the junction between lower
      7/9 and upper 2/9 of the lower leg, whereas probability of partial necrosis
      occurring in the flap increase significantly when the proximal tip of flap
      locates in upper 1/9 of the lower leg.

PMID- 21174786
TI  - [Treatment of chronic extremity lymphedema with manual lymph drainage].
AB  - OBJECTIVE: To evaluate the effect of manual lymph drainage on chronic extremity
      lymphedema. METHODS: Fifty patients with chronic lymphedema of extremity were
      treated with manual lymph drainage (MLD) complex decongestion therapy. Among
      them, 29 had primary lymphedema, 21 had secondary lymphedema. 42 had lymphedema
      of lower extremity and 8 had lymphedema of upper limb. The result of treatment
      was evaluated with measurement of circumference of extremities and edema fluid in
      tissue with Multiple-frequency bioelectrical impedance analysis. RESULTS: After 1
      2 treatment courses, all 50 patients showed significant decrease of circumference
      of lymphomatous limbs (P < 0.05) and remarkable reduction of accumulated edema
      fluid in tissue (P < 0. 05). There was highly correlation between the decrease of
      limb circumference and edema fluid in tissue (r(s) = 0.774, P < 0.01).
      CONCLUSIONS: MLD complex decongestion therapy is effective for the treatment of
      chronic lymphedema of extremity.

PMID- 21174787
TI  - [The morphological study on masseter muscle following mandibular angle
      osteotomy].
AB  - OBJECTIVE: To evaluate the morphological change of masseter after the mandibular
      angle osteotomy. METHODS: Computerized tomography (CT) examination was performed
      on 120 patients treated by mandibular angle osteotomy before operation and at 3,
      6, 12 months after operation, respectively. The pre- and postoperative masseter
      muscle thickness and cross-sectional area were evaluated using 3D CT images
      observed from 3 selected slice planes, which were paralleled with Frankfurt
      horizontal plane. These CT images were stored and three-dimensional
      reconstruction were made for calculation of masseter muscle volume through
      software. RESULTS: After operation, the reduction of the masseter muscle volume
      and cross-sectional area was seen. The volume of the masseter at 3, 6, 12 months
      postoperatively decreased to 82.02%, 77.00% and 80.43% (P < 0.05). The cross
      sectional area at 3, 6,12 months postoperatively decreased to 85.81%, 78.86% and
      81.56% at A plane, 80.94%, 75.03% and 77.04% at B plane, and reached to 13.46%,
      11.48% and 13.89% at C plane (P < 0.05, P < 0.05, P < 0.01). The masseter
      thickness after operation was significantly different from that before operation
      during the follow-up period, but not at 12 months after operation at A plane.
      CONCLUSIONS: The masseter atrophy happens spontaneously after mandibular angle
      osteotomy, especially at the region of mandibular angle. It should be considered
      during surgical design.

PMID- 21174788
TI  - [Change of zygomatic and temporal soft tissue after coronal incision].
AB  - OBJECTIVE: To investigate the change of zygomatic and temporal soft tissue after
      coronal incision. METHODS: A retrospective analysis was performed in 33 patients
      who received firm fixation for unilateral zygomatic comminuted fracture through
      semi-coronal incision. All the patients were followed up for more than one year.
      Craniofacial anthropometric measurement through 3D-CT reconstruction and facial
      profile was performed. The difference between the operated side and healthy side
      was analyzed. RESULTS: At the temporal concave point, the soft tissue thickness
      at healthy side was (1.60 +/- 0. 97) mm more than that at operated side, showing
      a significant difference between them (P < 0.01). While the soft tissue thickness
      was not statistically different between two sides at zygion, malar prominence,
      zygomaxillare, and temporal convex point (P > 0.05). CONCLUSIONS: The soft tissue
      atrophy may happen at temporal fat pad after semi-coronal incision, but not at
      zygomatic area. Intraoperative precise dissection and less stretch of soft tissue
      may be helpful to avoid the postoperative facial asymmetry.

PMID- 21174789
TI  - [Comparison study on the efficacy of three methods for the treatment of
      osmidrosis].
AB  - OBJECTIVE: To compare the efficacy of decollement, combined tumescent liposuction
      and curettage, Botox injection in the treatment of osmidrosis. METHODS: From
      September 2006 to April 2009, 350 patients with osmidrosis were treated by
      decollement method in 180 cases, curettage in 120 cases,and Botox injection in 50
      cases. The therapeutic effect and complications were retrospectively analyzed.
      RESULTS: The patients were followed up for 3-24 months. The cure rate was 90.6%,
      84.8% and 84.2% in decollement, curettage and Botox groups, respectively. The
      effective rate was 100% in all groups. CONCLUSIONS: All the three methods are
      effective for the treatment of osmidrosis. The odor symptom can be improved a lot
      with decollement method. Considering the complication, downtime and cosmetic
      results, Botox injection is suitable for patients with minor or median odor,
      while combined liposuction and curettage is selected for patients with median to
      severe odor.

PMID- 21174790
TI  - [Application of MDCT angiography for breast reconstruction with deep inferior
      epigastric artery perforator flaps].
AB  - OBJECTIVE: To investigate the significance of preoperative MDCT angiography for
      breast reconstruction with abdominal flap. METHODS: Preoperative MDCT angiography
      scans were performed on 34 patients who underwent breast reconstruction with
      abdominal flaps during December 2006 to June 2009. The operation was designed
      based on the MDCT results. Then the MDCT results were proved intraoperatively.
      Another 22 cases who underwent breast reconstruction with abdominal flap without
      preoperative MDCT were selected as controls. The rate of operative method change,
      the operation time and the flap necrosis were compared between the two groups.
      RESULTS: The preoperative design changed in 23.53% of the patients, based on the
      MDCT results. No one had any method change intraoperatively in the group with
      MDCT. The operative method was changed intraoperatively in 13.64% of the patients
      in the control group. The mean time spending on flap harvesting was (2.51 +/-
      0.64) h in the experimental group and (4.42 +/- 0.21) h in the controlled group
      (P < 0.05). The rate of complication was 6.12% in the experimental group and
      12.5% in the control group (P = 0.017). CONCLUSIONS: Preoperative MDCT
      angiography is an easy and reliable method for breast reconstruction with
      abdominal flap. The preoperative design can be more reasonable. It helps to save
      the operation time and reduce the risk.

PMID- 21174791
TI  - [3-Dimensional reconstruction of MR hydrography in patients after polyacrylamide
      hydrogel injection for augmentation mammoplasty].
AB  - OBJECTIVE: To investigate the diagnosis method in the patients after
      polyacrylamide hydrogel injection for augmentation mammoplasty for preoperative
      surgical design. METHODS: 3-dimensional reconstruction of Magnetic resonance
      hydrography (MRH) was performed on patients after polyacrylamide hydrogel
      injection for augmentation mammoplasty. The images were observed to understand
      the distribution and location of hydrogel. The operation was performed and guided
      by the images results. RESULTS: 7 patients underwent MRH examination and 6 cases
      received operation. The distribution and location of hydrogel was consistent with
      the MRH results. CONCLUSIONS: The distribution of hydrogel can be displayed
      clearly by 3D MRH reconstruction technique,and it is helpful to remove the
      hydrogel completely.

PMID- 21174792
TI  - [The reconstruction of large chest wall defect for 6 patients].
AB  - OBJECTIVE: To introduce the management of large chest wall defect. METHODS: From
      Oct. 2005 to Jun. 2009, 6 patients with large chest wall defects were
      reconstructed by latissimus dorsi muscle flap and titanium mesh in one case,
      reverse latissimus dorsi muscle flap and polypropylene mesh in one case, free
      lateral anterior thigh flap in one case, bilateral pectoralis muscle flap in one
      case, and vertical rectum abdominal muscle flaps in two cases. RESULTS: The
      patients were followed up for 1-24 months with good cosmetic and functional
      results. The flaps survived completely. One case of chest wall fistula and one
      case of sinus occurred, which healed after debridement. CONCLUSIONS: Every layers
      of chest wall defects should be reconstructed, respectively. The chest wall
      defects should be reconstructed by titanium mesh and polypropylene mesh first.
      The soft tissue defect should be covered with different flaps according to the
      location, area and the degree of the defects. Latissimus dorsi muscle flap can be
      as the first-line treatment with the advantages of good blood supply, flexible
      movement and abundant tissue volume.

PMID- 21174793
TI  - [Comparative study on repair of full-thickness burn wound with different
      artificial dermal stent in pigs].
AB  - OBJECTIVE: To compare differences of angiogenesis among collagen- chitosan,
      collagen-sulfonated carboxymethyl chitosan porous scaffolds and acellular dermal
      matrix after these three different scaffolds with silicone membrane were
      transplanted on the wounds of full thickness burn, and the wound repair of
      different scaffolds with epidermis grafting on. METHODS: Angiogenesis in
      different dermal scaffolds, the wound surface and epidermis survival were
      observed in 1, 2, and 3 weeks after the three different scaffolds were
      respectively transplanted on wounds of full thickness burn with debridement in 6
      Bama miniature pigs (total 18 pigs in 3 groups). At the same time, CD34 positive
      signals (neo-forming microvessels) were detected by immunohistochemical staining.
      The wounds without any scaffold transplantation were studied as the control.
      RESULTS: Angiogenesis had been fundamentally finished in 2 weeks after
      implantation of collagen- sulfonated carboxymethyl chitosan porous scaffold. And
      fundamental angiogenesis in collagen- chitosan porous scaffolds and acellular
      dermal matrix needed at least 3 weeks. Neo-forming micro-vessels perpendicular to
      wound beds with these three different scaffolds were more than those in the
      control wounds without scaffold. CD34 positive signals (neo-forming micro
      vessels) were significantly higher in wounds at the second week than those in
      wounds at the first week. And those in wounds at the third week were
      significantly higher than those in wounds at the second week in all wounds with
      different scaffold transplantations and the control wounds. CD34 positive signals
      in the group of sulfonated carboxymethyl chitosan porous scaffold on the 1st, 2nd
      and 3rd week after the scaffold transplantation were significantly higher than
      those corresponding signals in the other three groups. Epidermis on the
      sulfonated carboxymethyl chitosan porous scaffold which had been transplanted on
      burn wound for 1 week could survive perfectly, however, epidermis on the collagen
      chitosan porous scaffold or acellular dermal matrix could not survive until
      these two scaffolds had been transplanted on the burn wounds for at least 2
      weeks. CONCLUSIONS: These three different scaffolds could repair the full
      thickness skin defects caused by burn, and angiogenesis of sulfonated
      carboxymethyl chitosan porous scaffold is the best.

PMID- 21174794
TI  - [Construction of tissue-engineered skin by mix-seeding].
AB  - OBJECTIVE: To investigate the feasibility of construction of tissue-engineered
      skin in vitro. METHODS: Fibroblasts were seeded on the dermal surface of
      acellular dermal matrix (ADM). 7 days later, epidermal cells (5 x 10(5)/cm2) were
      mixed with fibroblasts (0.2 x 10(5)/cm2) and then seeded on epidermal surface of
      ADM. The culture medium was the mixture liquor containing K-SFM in half and the
      culture supernatants of fibroblasts in half. In the control group, only epidermal
      cells (5 x 10(5)/cm2) were seeded and cultured with K-SFM. After composite skin
      was cultured for 1 week and 3 week, samples were harvested respectively for
      morphological study and to receive identification by immunohistochemistry.
      RESULTS: After 3-week culture, there were 3-4 continuous layers of cells in the
      epidermis in the experiment group. The epidermis was attached tightly to the
      dermis with trochanterellus. But in the control group, there were just 1-2 layers
      of cells in the epidermis which was not connected to the dermis. Strong positive
      dye of Laminin indicated that basement membrane was thoroughly formed in the
      experiment group. The same result was demonstrated by transmission electron
      microscope. CONCLUSIONS: The mix-seeding of epidermal cells and few fibroblasts
      would promote the adhesion and proliferation of epidermal cells on ADM, and the
      formation of basement membrane.

PMID- 21174795
TI  - [Significance of the secreted frizzled-related protein 2 expression in earlobe
      keloid].
AB  - OBJECTIVE: To investigate the expression and the role of secreted frizzled
      related protein 2 (SFRP2) in the earlobe keloid and find a valid way to treat the
      keloid with gene therapy. METHODS: The expression of SFRP2 mRNA and protein was
      tested with in situ hybridization and Western Blot Analysis method in the
      different period of earlobe keloid. RESULTS: The SFRP2 mRNA and protein
      expression at the keloid edge was significantly high in 12 month group than in 3
      or 6 month groups (P < 0.01), but not than in 24 month group. The SFRP2
      expression started to decrease in the keloid center 12 month later (P < 0.01).
      The SFRP2 expression was always higher in edge than in center during all the
      period (P < 0.05, P < 0.01). CONCLUSIONS: The results suggest that SFRP2 may play
      an important role in the development of keloid, especially at the keloid edge.
      The high SFRP2 expression in endothelial cells and surrounding tissue is also
      important. It may be a new way for gene therapy of keloid by decreasing the SFRP2
      expression.

PMID- 21174796
TI  - [Preliminary comparison study of adipogenic differentiation capacity between
      dedifferentiated adipocytes cells and adipose-derived stem cells in vivo].
AB  - OBJECTIVE: To compare the adipogenic differentiation capacity of dedifferentiated
      adipocytes cells (DA) and adipose-derived stem cells (ASCs) in vivo, so as to
      select good adipogenic seed cells for tissue engineering. METHODS: Mature
      adipocytes and ASCs were isolated by means of enzymatic digestion from the
      liposuction aspirate. Then the DA cells were acquired by ceiling adherent culture
      of mature adipocytes and the 3rd passage cells were used. The DA cells and ASCs
      were cultured with fibrin glue in vitro respectively. The compatibility of
      scaffold with cells was detected by microscopy and scanning electron microscopy.
      The scaffold-cell composite was also labeled by DiI. The composite was injected
      subcutaneously on the nude mice back, respectively (DA-FG group, n = 8; ASCs-FG
      group, n = 8; sham FG group, n = 8). 8 weeks after implantation, the newly formed
      tissue was taken out for general observation and histologic study. RESULTS:
      Mature adipocytes were transferred to DA cells with spindle shape, like
      fibroblast. The ASCs were also spindle. Three days after culture of cell-scaffold
      composite in vitro, the cells grew well. 8 weeks after implantation, the newly
      formed tissue was found under the skin both in DA-FG and ASCs-FG groups, but not
      in sham FG group. The newly formed tissue was mature fat tissue and originated
      from the seed cells. The average wet weight of the new-formed tissue was higher
      in DA-FG group than that in ASCs-FG group. The average fibrosis ratio was lower
      in DA-FG than in ASCs-FG group. CONCLUSIONS: The tissue-engineered adipose tissue
      can be achieved with DA cells and ASCs as seed cells. Compared with ASCs, the new
      formed fat tissue with DA has a higher wet weight and lower fibrosis ratio.

PMID- 21174797
TI  - [Cold stress induces the suppression of splenic NK cell activity and the c-fos
      expression in rat brain].
AB  - AIM: To observe the effect of cold stress on the splenic NK cell activity and the
      c-fos expression in rat brain. METHODS: Rats were maintained in cold chamber at 4
      degrees for 4 h. The 51Cr release assay from YAC-1 cells was used to determine
      the splenic NK cell activity and the double staining of ABC method was employed
      to observe the immunoreactive expression of Fos, arginine-vasopressin and
      tyrosine hydroxylase. RESULTS: Cold stress could induce a marked suppression of
      splenic NK cell activity and a significant expression of Fos protein in
      hypothalamic paraventricular nucleus(PVN), as well as in the brainstem locus
      coeruleus (LC). Double staining showed c-expression of Fos and arginine
      vasopressin in some of PVN neurons, and co-expression of Fos and tyrosine
      hydroxylase in the majority of LC neurons. CONCLUSION: The vasopressinergic
      neurons in PVN and the catecholaminergic neurons in LC might be probably involved
      in the suppression of splenic NK cell activity induced by cold stress.

PMID- 21174798
TI  - [Effect of F89 on body v levels of Gaoyou duck].

PMID- 21174799
TI  - [The effect of motilin in PVN of hypothalamus on the gastric motility].
AB  - AIM: To investigate the role of motilin in paraventricular nucleus (PVN) of
      hypothalamus on the regulation of gastric motility and the mechanism. METHODS:
      Immunohistochemistry and microinjection of motilin into PVN were used to observe
      motilin neural cells in PVN, the neural path between PVN and dorsal vagal complex
      (DVC) and the changes of gastric motility in conscious rats. RESULTS: (1) There
      were motilin immunoreactive-cells in PVN and a significant increase was found in
      groups of fasting and HCL-perfusion into duodenum. (2) HRP-positive cells were
      found in PVN after microinjection HRP into dorsal nucleus of vagal nerve. It
      proved that there was neural relationship between PVN and DVC. (3) The amplitude
      and frequency of gastric motility increased significantly by microinjection
      motilin into PVN in conscious rats. The effects produced by motilin could be
      abolished by vagotomy. CONCLUSION: All these results presented imply that motilin
      in PVN may increase gastric motility through PVN-DVC-Vagal nerve axis.

PMID- 21174800
TI  - [Effect of fetus hypobaric hypoxia on NMDA receptor of hippocampus neurons].
AB  - AIM: To study the effect of fetus hypobaric hypoxia on the number and channel
      character of NMDA receptor of hippocampus neurons. METHODS: Use in situ
      hybridization and patch-clamp techniques. RESULTS: After hypobaric hypoxia the
      number of NMDA mRNA positive neurons was decreased, the open probability of NMDA
      receptor was reduced, the open time constant was decreased, the close time
      constant was increased. CONCLUSION: Hypobaric hypoxia may change the development
      of NMDA receptor in fetus rat, then maybe effect learning and memory.

PMID- 21174801
TI  - [Effects of wide band frequency noise on ERK, GDNF and ABR threshold in the
      different area of brain of AD rats poisoned by glutamatic acid].
AB  - AIM: To investigate the change of ERK, GDNF expression activity in temple and
      frontal lobe of AD rat after 96 dB wide band noise exposure. METHODS:
      Experimental group SD rats(weight from 150-220 g), either male or female, were
      randomly assigned to three groups: control (n=10); physiological brine-injected
      control (n=8); glutamic acid-injected group (n=8) after getting rid of memory
      loss(indicating "a little memory" and "no memory") rats culled by behavior
      training. The rats were micro-injected at the stereotaxic device (AP3.2-3.4, L2.0
      2.4,H2.8-3.0)by glutamic acid or same volume of physiological brine in the each
      side of hippocampus CA1. Western Blot and image quantitative analysis technique,
      combined with auditory brainstem response (ABR) measurement. RESULTS: (1)
      Expressions of ERK in frontal cortex for control rat are much more than that of
      other group, which has a obvious up-regulation after being given 96 dB noise.
      Expression of ERK in temple cortex for 3 groups rat have a increase(plus noise),
      moreover, they are stronger than expression in frontal cortex for different
      group. (3) GDNF in frontal cortex for control rat have a higher expression than
      that of the same group before adding noise (up-regulation). (4) GDNF expression
      in temple lobe for glutamatic acid group have a remarkable down-regulation trend.
      (5) Expression of GDNF in frontal for control rat is much less than in temple.
      CONCLUSION: ERK in frontal cortex for AD model rat have fewer expressions and not
      being affected by 96 dB noise, but it is reverse in temple. Wide band frequency
      noise can reduce the expression of GDNF in temple lobe of AD model rat.

PMID- 21174802
TI  - [Inducible nitric oxide synthase induces beta-amyloid neurotoxicity in vivo].
AB  - AIM: To investigate the causative role of nitric oxide synthase (NOS) and nitric
      oxide (NO) in neurotoxicity of beta-amyloid (Abeta) and the pathogenesis of
      Alzheimer's disease (AD). METHODS: Using behavioral and neuropathological
      methods, we observed the effects of Abeta(1-40) injection into hippocampi on rats
      learning and memory in Y maze and on the neuropathology in hippocampi. The
      intervention by intraperitoneal administration of aminoguanidine (AG), a
      selective inducible NOS (iNOS) inhibitor, and 7-nitroindazole (7-NI), a selective
      neuronal NOS (nNOS) inhibitor, in the neurotoxicity of Abeta(1-40) was studied
      then. RESULTS: The capability of acquisition and retrieval in Y maze and local
      neurons in hippocampus of the rats were impaired significantly after Abeta(1-40)
      injection. Intraperitoneal administration of AG, but not 7-NI, could prevent the
      damages caused by Abeta(1-40) injection above-mentioned. CONCLUSION: iNOS/NO
      participates in the mechanisms of Abeta-induced neurotoxicity and may play an
      important role in the pathogenesis of AD.

PMID- 21174803
TI  - [The effect of cyclooxygenase-2 on dopaminergic neurons in substantia nigra of
      Parkinson's disease mice induced by MPTP].
AB  - AIM AND METHODS: Using Strain C57/BL of COX-2 deficient mice, the effect of
      Cyclooxygenase-2 (COX-2) on dopaminergic neurons in substantia nigra of
      Parkinson's disease (PD) mice induced by intraperitoneal injections of MPTP-HCl
      were investigated by immunocytochemistry(ICC) . RESULTS: We found that the
      mortality in COX-2 heterozygous mice is much lower than that in wild type mice (P
      < 0.01) after injection of MPTP (30 mg/kg/day). The result of semiquantitative
      immunocytochemical staining showed that the number of tyrosine hydroxylase (TH)
      immunoreactive neurons in the substantia nigra pars compacta (SNc) declined more
      significantly in MPTP-treated wild type mice than that in COX-2 heterozygotes
      mice (P < 0.01). CONCLUSION: COX-2 may be related with lesion of dopaminergic
      neurons in the SNc of PD.

PMID- 21174804
TI  - [Cardiovascular responses to positive pressure breathing using two kinds of
      Jerkin-G-suit].

PMID- 21174805
TI  - [Subdiaphragmatic vagotomy reduces the responses of fever and discharge of
      neurons in PVN to LPS].
AB  - AIM: To study the possibility that responses of fever and discharge of neurons in
      PVN to intraperitoneal administration of LPS are mediated by vagal afferents.
      METHODS: Rectal temperature of rat was detected by digital temperature detecting
      instrument. Glass micropipette placed in PVN was used to record unit discharges
      of neurons in it, before and after LPS was injected into PVN in normal rats and
      vagotomy rats. RESULTS: The rectal temperature change value in vagotomy LPS group
      was significantly decreased compared with that in sham LPS group, and there was
      striking difference between them (P < 0.05). The discharges of neurons in PVN was
      increased in the normal rat in response to LPS. The discharges of neurons in PVN
      had no significant change in the vagotomy rats in response to LPS. CONCLUSION:
      The results indicate that vagus nerve may be one of the pathways of peripheral
      LPS signal communicating to CNS.

PMID- 21174806
TI  - [Protective effect of magnesium on hippocampal neurons damage induced by glutamic
      acid].
AB  - AIM: To investigate the effect of magnesium ion (Mg2+) on neuronic damage induced
      by 0.1 mmol/L glutamic acid. METHODS: The neurons isolated from hippocampus in
      rats were cultured for 6-9 days, and then randomly divided into three groups: A.
      medium alone. B. medium + glutamic acid. C. medium+ Mg2+, and + glutamic acid (30
      min late). RESULTS: (1) DAs compared with A group, the survival rate of
      hippocampal neurons in B group was remarkably decreased in dose dependent mauner.
      (2) In contrast to B group, when the concentration of Mg2+ was lower, the
      survival rates of hippocampal neurons in C group was significantly increased.
      CONCLUSION: Mg2+ in lower concentration could protect hippocampal neurons from
      damage induced by glutamic acid.

PMID- 21174807
TI  - [Differentially display of genes in hypothalamus of heat acclimated rats].

PMID- 21174808
TI  - [Effects of interleukin-2 on ventricular papillary muscle of rat and the possible
      mechanism].
AB  - AIM: To investigate the effects of interleukin-2 (IL-2) on the transmembrane
      potential and contractile force in ventricular papillary muscle of rat and the
      underlying mechanism. METHODS: The transmembrane potentials and contractile force
      were recorded by intracellular glass microelectrode and tension transducer in the
      isolated rat papillary muscles. RESULTS: (1) IL-2 shortened the action potential
      duration (APD50 and APD80), while had no effects on resting potential, action
      potential amplitude and depolarization rate. (2) IL-2 depressed the contractile
      force of the muscle in dose-dependent manner. IL-2 at concentrations of 0.5, 2.5,
      10, 50 and 200 u/ml decreased the developed tension to 94.8% (P < 0.05), 85.8%,
      76.3%, 69.3% and 52.5% (P < 0.01), respectively. (3) Pretreatment with L-NAME
      (10(-4) mol/L) attenuated the negative inotropic effect of IL-2, in which effect
      of IL-2 at concentrations from 0.5 to 10 u/ml was completely abolished, and the
      effect of IL-2 at high dose (50 and 200 u/ml) was partly attenuated by L-NAME.
      CONCLUSION: IL-2 had inhibitory effects on action potential duration and
      contractile force of papillary muscle, and its negative inotropic effect was
      mediated by nitric oxide.

PMID- 21174809
TI  - [Effects of avian pancreatic polypeptide (APP) on the secretive functions of
      cultured hepatocytes of rats].

PMID- 21174810
TI  - [Mechanisms of protection effect of bcl-2 gene transfection on heat-stressed
      cardiomyocytes].
AB  - AIM: To study the mechanisms of protection of bcl-2 gene transfection against
      heat-stressed cardiomyocytes. METHODS: Cardiomyocytes were isolated and cultured.
      bcl-2 was transfected into cardiomyocytes with Lipofectamine transfection
      methods. The cardiomyocytes were stressed by heat. The change of H+ -ATPase
      synthesis activity of cardiomyocytes mitochondria caused by bcl-2 transfection
      was measured by chemical radiation method. The changes of Caspase 3 activity of
      cardiomyocytes caused by bcl-2 transfection was measured by fluorometric
      analysis. RESULTS: bcl-2 transfection could increase the H+ -ATPase synthesis
      activity of cardiomyocytes mitochondria under heat stress at 41 degrees C and 43
      degrees C and could decrease the Caspase 3 activity of cardiomyocytes under heat
      stress at 41 degrees C and 43 degrees C. CONCLUSION: The protection effect of bcl
      2 transfection on heat-stressed cardiomyocytes may be associated with preserved
      H+ ATPase synthesis activity of cardiomyocytes mitochondria and the activity of
      Caspase 3 of cardiomyocytes.

PMID- 21174811
TI  - [Effect of vasonatrin peptide on the expression of C-type natriuretic peptide
      receptor in hypoxic rat hearts].
AB  - AIM: To investigate the effect of vasonatrin peptide (VNP) on the expression of C
      type natriuretic peptide receptor (NPR-C) in hypoxic rat hearts. METHODS: Rats
      were divided randomly into three groups: control group, hypoxia group(3-28 d) and
      VNP (25-75 microg/kg per day) + hypoxia group. The plasma concentration of atrial
      natriuretic peptide (ANP) in rats was measured by the means of radioimmunoassay.
      Furthermore, quantitative PCR was used to examine the NPR-C mRNA level in rat
      hearts. RESULTS: The plasma concentration ANP in rats was significantly higher
      than that of control group, and VNP (75 microg/kg per day) made it more higher.
      Hypoxia for 3 day of had no significant effect on the NPR-C mRNA level in rat
      hearts, while hypoxia for 7-28 d significantly increased the level of NPR-C mRNA
      in a time dependent manner. VNP (50-75 microg/kg per day) significantly reduced
      the NPR-C mRNA level in rat hearts in a dose dependent manner. CONCLUSION: VNP
      increases the plasma concentration of ANP in hypoxic rats. Hypoxia can increase
      expression of NPR-C in rat hearts significantly, which can be inhibited by VNP.

PMID- 21174812
TI  - [Study on the origin and conductive features spinal cord motor evoked potentials
      in rat].

PMID- 21174813
TI  - [Modulation of protein kinase A and protein kinase C on the delayed rectifier
      potassium current in guinea pig ventricular myocytes].
AB  - AIM: To study modulation of protein kinase A (PKA) and protein kinase C (PKC) on
      the delayed rectifier potassium current (Ik)in guinea pig ventricular myocytes.
      METHODS: The delayed rectifier potassium current was recorded by using whole cell
      arrangement of the patch-clamp procedure. RESULTS: cAMP 150 micromol/L increased
      intracellularly Ik and Ik,tail(pA/pF) from 13.7 +/- 2.1 and 6.1 +/- 0.1 to 18.5
      +/- 3.3 and 6.4 +/- 2.1 (P < 0.01, n=6). Ik and Ik,tail(pA/pF) were augmented by
      8-CPT-cAMP 150 micromol/L extracellularly from 11.4 +/- 1.8 and 5.3 +/- 0.6 to
      17.9 +/- 4.0 and 6.2 +/- 1.3. The half-maximal voltage of activation of Ik was
      shifted from + 23.3 mV to 18.7 mV by cAMP. Phorbol 12-myristate 13-acetate(PMA,
      10.0 micromol/L) applied intracellularly caused an enhance effect on Ik, with
      increasing Ik and Ik,tail(pA/pF) from 12.9 +/- 1.8 and 5.0 +/- 1.7 to 23.7 +/-
      2.8 and 7.5 +/- 1.1. With shifting position potential of depolarization, effect
      of PMA on Ik was gradually augmented. PMA resulted in shifting the slop of
      activation curve from +15.3 mV to +25.6 mV, with only a small effect on the half
      maximal voltage of activation of Ik. CONCLUSION: Ik was increased by both PKA and
      PKC, with different characteristics of regulation.

PMID- 21174814
TI  - [Inhibitory effects of kappa-opioid receptor stimulation on cultured myocardial
      cells].
AB  - AIM: In order to study the effects of kappa-opioid receptor activation, we used
      cultured cardiomyocytes to study the inhibitory effects of U50,488H on cellular
      proliferation, protein content in the presence or absence of nor-binaltorphimine
      (nor-BNI). METHODS: The cellular proliferation was determined with crystal violet
      staining and the protein content was assayed with Lowry's method. RESULTS: A
      kappa-opioid receptor agonist U50,488H at 0.1 micromol/L-10 micromol/L inhibited
      the cellular proliferation and protein content of cultured myocardial cells in a
      dose-dependent manner. The inhibitory effects of U50,488H were completely blocked
      by pretreatment with nor-BNI, a specific kappa-opioid receptor antagonist at 1
      micromol/L. CONCLUSION: U50,488H inhibited the cultured myocardial cells' growth.
      The inhibitory effects of U50,488H are involved in mediating the action of kappa
      opioid receptor stimulation.

PMID- 21174815
TI  - [Effect of AVP V1 receptor antagonist on chlorpyrifos-induced hypothermia in body
      temperature in the rat].

PMID- 21174816
TI  - [Effects of different temperature and time on the period of validity and quality
      in blood preservation].
AB  - AIM: To examine the effects of different temperature protection on measures on
      preservation damages in liquid blood and explore the corresponding. METHODS: Take
      equal half blood samples from 10 healthy blood donors and divided each sample
      into two groups, put the fresh blood into CP2D-A solution at 0 degrees C and 4
      degrees C, respectively and take the samples 21 days and 42 days, later and then
      measured the contents of membrane phospholipids with shafig-UR-rehman method, CaM
      with purification PED test, LPO with spectrophotometry. RESULTS: At the same
      temperature, when the preservation time was prolonged, peroxidation was
      increased, the preservation damages were also augmented; the damages were
      declined when the temperature was lower during the same period, the aging of
      blood was more evident at 4 degrees C. CONCLUSION: Blood peroxidation temperature
      is lower. The author pointed out the questions and prospects of blood
      preservation.

PMID- 21174817
TI  - [The study on expression of heme oxygenase-1 in the peripheral blood mononuclear
      cell from asthmatic patients].
AB  - AIM: To explore the expression of heme oxygenase-1 (HO-1) in the peripheral blood
      mononuclear cell (PBMC) and relationship to ventilatory function in asthmatic
      patients. METHODS: Eighteen asthmatic patients and eighteen healthy subjects were
      selected. HO-1 protein levels in PBMC were measured by immunohistochemical
      staining and PBMC HO-1 mRNA were determined by reverse transcription-polymerase
      chain reaction (RT-PCR), blood carbon monoxide Hb (COHb) percent value, serum
      total IgE concentration and pulmonary ventilatory function were observed in
      asthmatic patients and healthy subjects. RESULTS: The percentage of cells in
      immunohistochemical staining positive staining of HO-1 were significantly higher
      in asthmatic patients (41.7 +/- 7.44%) compared with that of healthy subjects
      (10.5 +/- 4.36%, P < 0.01), the optical densities of PBMC HO-1 mRNA were higher
      in asthmatic patients (26.05 +/- 4.14) compared with that of healthy subjects
      (10.82 +/- 4.26, P < 0.01). The relation analysis showed PBMC HO-1 protein levels
      had significantly negative relation with FEV1, PEFR, MEFR50%, respectively (r = 
      0.89, -0.56, -0.51, P < 0.01, respectively) and positive relation with COHb
      percent value, serum total I gE concentration (r = 0.80, 0.48, P < 0.05,
      respectively), and PBMC HO-1 mRNA levels had significantly negative relation with
      FEV1, PEFR, MEFR50%, respectively (r = -0.89, -0.65, -0.67, P < 0.05,
      respectively) and positive relation with COHb percent value, serum total IgE
      concentration (r = 0.85, 0.62, P < 0.01, respectively). CONCLUSION: The
      expression of PBMC HO-1 protein and mRNA are increased significantly in asthmatic
      patients, HO-1 may play a significant role in the pathogenesis of asthma. The
      expression of HO-1 has relation with severity of asthma.

PMID- 21174818
TI  - [The role of N-acetylcysteine against the injury of pulmonary artery induced by
      LPS].
AB  - AIM: To investigate the alleviating effect of N-acetylcysteine (NAC) on lung
      injury induced by lipopolysaccharides (LPS) and its mechanism. METHODS: The
      effects of NAC on changes of the pulmonary arterial reactivity and the
      ultrastructure of pulmonary arterial endothelium induced by LPS were observed
      with the isolated artery ring technique and scanning electron microscope (SEM).
      Malondialdehyde (MDA), nitric oxide (NO) contents and superoxide dismutase (SOD)
      activity of pulmonary artery tissues were detected. RESULTS: The exposure of
      pulmonary artery to LPS (4 microg/ml, 7 h) led to reduction of endothelium
      dependent relaxation response to acetylcholine (ACh), which was reversed by the
      concomitant exposure to NAC (0.5 mmol/L, 7 h), whereas NAC itself had no effect
      on the response. Significant structural injury were observed under SEM in LPS
      group and alleviated the changes in LPS + NAC group. The MDA, NO contents
      increased but SOD activity decreased in LPS group, which were reversed by the
      concomitant exposure to NAC. CONCLUSION: NAC protects pulmonary artery
      endothelium and enhances endothelium-dependent relaxation response of pulmonary
      artery by antioxidation effect, which may be one of the mechanisms of its
      reversing pulmonary artery hypertension and following lung injury induced by LPS.

PMID- 21174819
TI  - [The expression of CD4, CD8, on mice T cells after ultraviolet irradiation].

PMID- 21174820
TI  - [The role of endogenous carbon monoxide in vascular remodeling in hypoxic
      pulmonary hypertension].
AB  - AIM: To investigate the expression of heme oxygenase-1 gene and production of
      endogenous carbon monoxide in the rat lung tissue at different time points of
      chronic hypoxic pulmonary hypertension and the effect of hemin, an inducer of
      heme oxygenase, on the expression of HO-1 gene and production of endogenous
      carbon monoxide and pulmonary hypertension. METHODS: We recreated a rat model of
      hypoxic pulmonary hypertension by intermittent normal pressure hypoxia (10% O2).
      The following assays were carried out: Reverse transcriptase polymerase chain
      reaction (RT-PCR) were performed to determine the level of HO-1 mRNA in rat lung
      tissue, double wave length spectrophotometry was used to evaluate the quantity of
      COHb in arterial blood, cardiac catheterization was used to measure the right
      ventricular systolic pressure (RVSP) and HE staining was performed in dissected
      lung tissue to observe the pathologic changes of the intra-acinar pulmonary
      arteries(IAPA). RESULTS: (DT here was low level of HO-1 mRNA in normal rat lung
      tissue, but the level of HO-1 mRNA increased by 2-4 times in the lung tissue of
      hypoxic rats (P < 0.01). The quantity of COHb was 2-3 times as those of control
      group (P < 0.01 or P < 0.05). These were accompanied by the increase of RVSP and
      the thickness of IAPA. (2) Hemin could maintain the HO-1 mRNA and COHb in the
      hypoxic rat lung tissue at a high level, and partially suppressed the increase of
      rat RVSP, ameliorated the pathologic changes of IAPA. CONCLUSION: The
      upregulation of the expression of HO-1 gene and production of CO in the rat lung
      of hypoxic pulmonary hypertension plays a role of inhibition in the development
      of hypoxic pulmonary hypertension. Hemin has a therapeutic effect on hypoxic
      pulmonary hypertension.

PMID- 21174821
TI  - [The protection effect of BDNF mediated by adenovirus to the serum free cultured
      SH-SY5Y cells].
AB  - AIM: To study the protective effect of adenovirus mediated brain derived
      neurotrophic factors on nerve injury. METHODS: SH-SY5Y cells were infected by the
      recombinant Ad-BDNF. In the serum-free condition, the morphological changes were
      observed, and MTT method was used to examine the trophic effects of different
      dosages of Ad-BDNF. The whole cells DNA of infected and control groups were
      extracted to detect the DNA ladder--the marker of apoptosis. RESULTS AND
      CONCLUSION: The adenoviruses mediated BDNF gene promoted the cell survival and
      differentiation. It also inhibited the serum-deprived induced cell apoptosis.

PMID- 21174822
TI  - [Comparative study on the antioxidant capacity of quercetin in vivo and in
      vitro].
AB  - AIM: To compare the TAOC of quercetin, rutin, vitamin C, vitamin E in vitro and
      examine the effect of quercetin on TAOC of rat plasma after intragastric
      administration. METHODS: Fe3+ reducing ability assay, UV spectrum analysis and
      HPLC analysis were used to measure TAOC of plasma and the contents of quercetin
      and rutin after intragastric administration. RESULTS: The TAOC of quercetin was
      stronger than that of rutin and roughly equal to vitamin C and vitamin E in
      vitro. After intragastric administration of quercetin (40 mg/kg bw), the TAOC and
      content of quercetin in rat plasma increased significantly. Vitamin C also
      increased plasma TAOC significantly, but rutin and vitamin E didn't after
      intragastric administration. However, there was no remarkable absorption peak of
      quercetin on HPLC chromatograms and on the other hand, the peak areas of two
      unknown peaks near quercetin peak were increased after intragastric
      administration of quercetin. CONCLUSION: The antioxidant capacity of quercetin
      was stronger than rutin and comparable to vitamin C both in vitro and in vivo.
      After absorption, quercetin is metabolized to its derivatives.

PMID- 21174823
TI  - [Change of serum leptin and leptin receptors immunoreactivity in the brain
      following intraoral infusions of chemical solutions in rats].
AB  - AIM: To determining whether the level of serum leptin altered and whether the
      expression of leptin receptor immunoreactivity changed following taste stimuli.
      METHODS: After intraoral infusions of chemical solutions, which included 3 mol/L
      sucrose, 5 mmol/L sodium saccharin, 0.1 mol/L NaCl, 0.01 mol/L HCl, 1 mmol/L
      quinine H2SO4 and 0.1 mol/L monosodium glutamate, serum leptin concentration were
      measured by using rat leptin RIA kit. Immunohistochemistry ABC method was used
      for brain sections with high-specify-goat antiserum against leptin receptors.
      RESULTS: Comparing with the control group (intraoral infusion of distilled
      water), the level of serum leptin only in sweet group (sucrose an d saccharin)
      raised (P < 0.05). Many neuronal cell bodies and dendritic processes showed
      leptin receptors immunoreactivity (LR-IR) in many brain regions, such as
      amygdala, hypothalamus, parabrachial nucleus and nucleus of the solitary tract,
      which had intense relationship with taste and feeding. But the number of positive
      stained cells showed no difference in aforementioned brain regions between the
      taste stimuli group and the control group. CONCLUSION: After intraoral stimuli of
      sweet substances, the serum leptin concentration increased. LR-IR cells exist in
      amygdala which plays a critical role in the initiation and guidance of feeding.
      This findings led us study possible effects of leptin on taste responses.
      Probably, leptin influences food intake through the sense of taste.

PMID- 21174824
TI  - [Inhibitory action of metoprolol and gamma--aminobutyric acid on heart rhythm
      disorder induced by administration of endothelin-1 into rostral ventrolateral
      medulla in cats].

PMID- 21174825
TI  - [The change of cholesterol level and Na+ -K+ -ATPase activity of erythrocyte
      membrane in early stage of severe burn patients].
AB  - AIM: To study the relationship between erythrocyte filtration index (EFI) and
      cholesterol and Na+ -K+ -ATPase activity of erythrocyte membrane in early stage
      of severe burns. METHODS: The EFI was measured by means of percolation, the
      erythrocyte membrane cholesterol level was measured by means of chemically
      modified electrode, and the membrane Na+ -K+ -ATPase activity by means of
      detection of Pi. RESULTS: In early stage of severe burns, the cholesterol level
      and Na+ -K -ATPase activity of erythrocyte membrane were always higher than those
      of control group (P < 0.01), but the EFI was lower than that of control group (P
      < 0.01). The cholesterol level and Na+ -K+ -ATPase activity of the erythrocyte
      membrane were negative correlation with EFI (r cho= -0.871, r ATPase = -0.801, P
      < 0.01) nospectively. CONCLUSION: The cholesterol level and Na+ -K+ -ATPase
      activity of erythrocyte membrane play a key role in the change of EFI.

PMID- 21174826
TI  - [The influences of RN stimulation on the c-responses of WDR in rat].

PMID- 21174827
TI  - [Measurement of nitrate and nitrite concentrations in biological fluids using
      high performance liquid chromatography].
AB  - AIM AND METHODS: New method to analyse nitrate and nitrite concentrations in
      saliva, serum and urine was developed using high performance liquid
      chromatography. RESULTS: The whole isolation process was completed in less than 7
      minutes, the determination linearity of nitrate and nitrite were 0.7 ng-100 ng
      and 5 ng-100 ng, respectively. MINIMUM: Detectable limits of nitrate and nitrite
      were 0.3 ng and 2 ng, respectively. Nitrate recovery ratio was 99%-102% and
      nitrite recovery ratio was 99%-104%. The RSD of nitrate and nitrite was 0.8% and
      1.7%, respectively. CONCLUSION: In comparison with other methods available, the
      present method seems to be simpler, more sensitive and specific.

PMID- 21174828
TI  - [Effects of 50 Hz-filter circuit on cardiac action potential recording and
      analyzing].
AB  - AIM: To study the effects of the 50 Hz-filter circuit in a microelectrode
      amplifier on cardiac action potential waveform and parameters. METHODS: Cardiac
      action potential signals were fed into a microcomputer through a glass
      microelectrode, a microelectrode amplifier, a differentiator and A/D converter.
      The cardiac action potential signals were recorded and analyzed with 50 Hz-filter
      circuit and without it, and the frequency spectrum in the signals was analyzed
      with the fast Fourier transformation. RESULTS: When the 50 Hz-filter circuit was
      used, the phase 0 of the potential waveform was seriously distorted and
      prolonged. The maximal rate of depolarization at the phase 0 was cut down, while
      the other parameters were not effected. CONCLUSION: There has already been much
      50 Hz element in the action potential waveform. During amplifying the cardiac
      action potential signal, the 50 Hz-filter circuit should not be turned on.
      Otherwise, the experiment results will be effected.

PMID- 21174829
TI  - [Effects of dopamine receptors inhibited rats caudate nucleus on the pressor
      effect of substantia nigra].

PMID- 21174830
TI  - [Protective effect of myocardium injury induced by stress using Chinese medicine
      compound--zhengxinli].

PMID- 21174831
TI  - [Regulation of glial fibrillary acidic protein gene by scorpion venom against
      epileptic seizures].

PMID- 21174832
TI  - [Facing the "longevity risk"].

PMID- 21174833
TI  - [Vaccination: a programme for the whole life].
AB  - In 2010 in Switzerland, vaccine-preventable infectious diseases still cause a
      significant morbi-mortality, notably among old adults. While the vaccination
      based prevention in the aged population has been neglected for a long time, the
      two European geriatrics and gerontology societies, EUGMS, IAGG-ER has recently
      proposed a vaccine schedule dedicated to adults aged over 60 and promote a life
      course vaccination programme. To convince of the importance of such measures in
      Switzerland, this article: recounts the beneficial impact of vaccines on the
      incidence of measles, pertussis, diphtheria, tetanus as well as influenza and
      pneumococcal diseases; presents the burden of these infectious diseases among the
      population no or insufficiently immunized; demonstrates that vaccinating in the
      respect of a life-course vaccine programme will reduce considerably the burden of
      these infectious disease.

PMID- 21174834
TI  - [Anemia in the elderly: a frequent condition that should not be overlooked].
AB  - Anemia is a frequent disease in elderly persons, but is often undertreated and
      misunderstood as a physiologic consequence of aging. Nevertheless, its
      association with some negative clinical impacts is well known and widely
      documented in the literature.

PMID- 21174835
TI  - [Practical picking up of elderly people in case of falls].
AB  - Falls in old persons are now considered as a "true" geriatric syndrome, because
      are frequent, multi-factorial with severe outcomes: increased morbidity,
      functional inabilities and mortality. In our current health care system, the
      primary care physician is the first to detect the fall and indeed to manage and
      coordinate the various interventions of the multiple healthcare professionals. To
      be effective, he needs simple screening tools, and also structured procedures as
      well as the support of specialized networks of care. However the current offer is
      highly variable from one canton to another. This article tries to provide
      validated screening tools to the primary care physician and useful contact
      addresses of public associations and services able to favor home care support.

PMID- 21174836
TI  - [Miliary tuberculosis: unexpected autopsy finding in an elderly person].
AB  - Miliary tuberculosis is a rare disease that is difficult to diagnose because of
      its non-specific presentation. It should be suspected in elderly patients who
      complaint of failure to thrive, unexplained fatigue and weight loss. Using a
      clinical situation where the diagnosis was made only at autopsy, we briefly
      review the epidemiology of miliary tuberculosis and propose recommendations for
      the diagnosis and the prophylaxis of latent tuberculosis. Finally, we discuss
      criteria to perform epidemiological investigations among close contacts in this
      situation.

PMID- 21174837
TI  - [Preventive approaches to dementia].
AB  - Prevalence and incidence of dementia increase with demographic aging. Benefits of
      current antidementia drugs are modest, both in cognitive and functional domains.
      Therefore, interest is growing to evaluate the effects of interventions aiming at
      preventing cognitive decline and, ideally, dementia onset. Cognitive training and
      physical activity seem promising. This paper describes recent studies that
      assessed the benefits of preventive strategies in the domain of dementia,
      especially in Alzheimer's disease.

PMID- 21174838
TI  - [From loss of autonomy to dysautonomia: anticholinergic drugs in geriatrics].
AB  - Elderly patients represent a huge market for the pharmaceutical industry because
      population is aging and multimorbidity is concentrated on the last years of life.
      The risk of inappropriate prescribing is high in this age group. Among the
      potentially toxic drugs, antimuscarinics occupy a prominent place. It should be
      necessary as far as possible to avoid them, especially if treatments are
      illogical. In the case of incontinence due to prostatic disease anticholinergic
      drugs usually worsen the problem. In patients with dementia, they have an
      opposite effect to inhibitors of acetylcholinesterase. Where no alternatives
      exist, it is recommended to make short term treatments and to reassess
      periodically the indication.

PMID- 21174839
TI  - [Echoes of the ESC 2010. Atrial fibrillation, rush on antiplatelet agents,
      genetics omnipresence].

PMID- 21174840
TI  - [Poor LAMal!].

PMID- 21174841
TI  - [Infertility is not fatality].

PMID- 21174842
TI  - [On commotion and on prostitution].

PMID- 21174843
TI  - [Cancer: a new identified biomarker].

PMID- 21174844
TI  - [The world before autonomy].

PMID- 21174845
TI  - [Promoting personal responsibility].

PMID- 21174846
TI  - [The future lies in networks].

PMID- 21174847
TI  - [Live-in employees in Swiss households].

PMID- 21174848
TI  - [Child friendly nursing care].

PMID- 21174849
TI  - [Nursing and social work together].

PMID- 21174850
TI  - [Living safely with a transplanted kidney].

PMID- 21174851
TI  - ["I know how important nurses are" (interview by Francois Taillens)].

PMID- 21174852
TI  - [Regional counseling of and for patients with a brain injury. Comprehensive
      support for patients with a brain injury].

PMID- 21174853
TI  - [Presidents and other personalities].

PMID- 21174854
TI  - [Discharge after epileptic seizure. Reporting abusive termination].

PMID- 21174855
TI  - [Nursing disabled elderly patients at home. Wish for respite offers].

PMID- 21174856
TI  - [From baby boom to mamy boom].

PMID- 21174857
TI  - [Aid and ambulatory care. Aging at home - the pleasure of remaining at home].

PMID- 21174858
TI  - [Research on agitation. Reflexology enters intensive care].

PMID- 21174859
TI  - [Preventing HIV/AIDS in immigrants. Three illustrated stories pass the message].

PMID- 21174860
TI  - [Nursing competence. Accommodating the psychotic experience as an act of nursing
      care].

PMID- 21174861
TI  - [The desire for autonomy must be defended and respected].

PMID- 21174862
TI  - Proceedings of the 21st Ljudevit Jurak International Symposium on Comparative
      Pathology. June 4-5, 2010. Zagreb, Croatia.

PMID- 21174863
TI  - Melanoma-targeted therapy based on V600E BRAF mutation.

PMID- 21174864
TI  - Trastuzumab for HER2-positive gastric and gastroesophageal junction cancers.

PMID- 21174865
TI  - Routes to low mortality in poor countries revisited.
AB  - In June 1986, Population and Development Review published a highly influential
      article by John Caldwell entitled "Routes to Low Mortality in Poor Countries."
      Amid growing anxiety over decelerating world mortality decline, Caldwell explored
      social and political pathways to mortality success on the basis of two lists of
      superior mortality achievers and exceptionally poor mortality achievers,
      countries whose mortality rankings drastically differed from their income
      rankings. To mark the quarter-century since Caldwell's study and chart new
      pathways, this article looks at the subsequent performance of Caldwell's original
      exceptional achievers and develops an updated list of achievers. Analysis
      highlights the presence of many more poor achievers today; the rising importance
      of adult mortality as a marker of exceptional achievement; the increasing success
      of countries in Latin America and the Muslim world; the continued success of
      China, Vietnam, Cuba, and Costa Rica. dramatic improvements in schooling
      outcomes, particularly for women, have reduced the importance of education as a
      determinant of superior achievement. Reinforcing Caldwell's original assertions,
      the synthesis highlights how interactions between social consensus, health care
      systems, and human capital dependence offer a pathway to superior achievement.
      These forces may be especially powerful at moments of national crisis.

PMID- 21174866
TI  - Food security in an era of economic volatility.
AB  - This article analyzes international commodity price movements, assesses food
      policies in response to price fluctuations, and explores the food security
      implications of price volatility on low-income groups. It focuses specifically on
      measurements, causes, and consequences of recent food price trends, variability
      around those trends, and price spikes. Combining these three components of price
      dynamics shows that the variation in real prices post-2000 was substantially
      greater than that in the 1980s and 1990s, and was approximately equal to the
      extreme volatility in commodity prices that was experienced in the 1970s. Macro
      policy, exchange rates, and petroleum prices were important determinants of price
      variability over 2005-2010, highlighting the new linkages between the agriculture
      energy and agriculture-finance markets that affect the world food economy today.
      These linkages contributed in large part to misguided expectations and
      uncertainty that drove prices to their peak in 2008. The article also argues that
      there is a long-lasting effect of price spikes on food policy around the world,
      often resulting in self-sufficiency policies that create even more volatility in
      international markets. The efforts by governments to stabilize prices frequently
      contribute to even greater food insecurity among poor households, most of which
      are in rural areas and survive on the margin of net consumption and net
      production. Events of 2008-and more recently in 2010-underscore the impact of
      price variability for food security and the need for refocused policy approaches
      to prevent and mitigate price spikes.

PMID- 21174868
TI  - Legislation to stimulate investment in comprehensive workplace health promotion
      programs.

PMID- 21174867
TI  - Child-care availability and fertility in Norway.
AB  - The child-care and fertility hypothesis has been in the literature for a long
      time and is straightforward: As child care becomes more available, affordable,
      and acceptable, the antinatalist effects of increased female educational
      attainment and work opportunities decrease. As an increasing number of countries
      express concern about low fertility, the child-care and fertility hypothesis
      takes on increased importance. Yet data and statistical limitations have
      heretofore limited empirical tests of the hypothesis. Using rich longitudinal
      data and appropriate statistical methodology, We show that increased availability
      of child care increases completed fertility. Moreover, this positive effect of
      child-care availability is found at every parity transition. We discuss the
      generalizability of these results to other settings and their broader importance
      for understanding variation and trends in low fertility.

PMID- 21174869
TI  - US mortality in an international context: age variations.
AB  - Compared to other developed countries, the United States ranks poorly in terms of
      life expectancy at age 50. We seek to shed light on the US's low life expectancy
      ranking by comparing the age-specific death rates of 18 developed countries at
      older ages. A striking pattern emerges: between ages 40 and 75, US all-cause
      mortality rates are among the poorest in the set of comparison countries. The US
      position improves dramatically after age 75 for both males and females. We
      consider four possible explanations of the age patterns revealed by this
      analysis: (1) access to health insurance; (2) international differences in
      patterns of smoking; (3) age patterns of health care system performance; and (4)
      selection processes. We find that health insurance and smoking are not plausible
      sources of this age pattern. While we cannot rule out selection, we present
      suggestive evidence that an unusually vigorous deployment of life-saving
      technologies by the US health care system at very old ages is contributing to the
      age-pattern of US mortality rankings. Differences in obesity distributions are
      likely to be making a moderate contribution to the pattern but uncertainty about
      the risks associated with obesity prevents a precise assessment.

PMID- 21174870
TI  - The educational gradient of childbearing within cohabitation in Europe.
AB  - Nearly every European Country has experienced some increase in nonmarital
      childbearing, largely due to increasing births within cohabitation. Relatively
      few studies in Europe, however, investigate the educational gradient of
      childbearing within cohabitation or how it changed over time. Using retrospective
      union and fertility histories, we employ competing risk hazard models to examine
      the educational gradient of childbearing in cohabitation in eight countries
      across europe. In all countries studied, birth risks within cohabitation
      demonstrated a negative educational gradient. When directly comparing cohabiting
      fertility with marital fertility, the negative educational gradient persists in
      all countries except Italy, although differences were not significant in Austria,
      France, and West Germany. To explain these findings, we present an alternative
      explanation for the increase in childbearing within cohabitation that goes beyond
      the explanation of the Second Demographic Transition and provides a new
      interpretation of the underlying mechanisms that may influence childbearing
      within cohabitation.

PMID- 21174871
TI  - The relative effects of shocks in early- and later-life conditions on mortality.
AB  - The relative importance of cohorts' early-life conditions, compared to later
      period conditions, on adult and old-age mortality is not known. This article
      studies how cohort-level mortality depends on shocks in cohorts' early- and later
      life (period) conditions. I use cohorts' own mortality as a proxy for the early
      life conditions, and define shocks as deviations from trend. Using historical
      data for five European Countries i find that shocks in early-life conditions are
      only weakly associated with cohorts' later mortality. This may be because
      individual-level health is robust to early-life conditions, or because at the
      cohort level scarring, selection, and immunity cancel each other. Shocks in
      period conditions, measured as deviations from trend in period child mortality,
      are strongly and positively correlated with mortality at all older ages. The
      results suggest that at the cohort level changing period conditions drive
      mortality variation and change.

PMID- 21174872
TI  - Are sports overemphasized in the socialization process of African American males?
      A qualitative analysis of former collegiate athletes' perception of sport
      socialization .
AB  - Scholars have noted that an elevated level of sports socialization in the family,
      neighborhood, and media exists within the African American community, creating an
      overrepresentation of African American males in certain sports. As a result,
      African American males may face consequences that are distinctly different from
      the consequences of those who are not socialized as intensively toward athletics,
      such as lower levels of academic achievement, higher expectations for
      professional sports careers as a means to upward mobility, and lower levels of
      career maturity. This study examines the sport socialization of African American
      male former collegiate athletes through in-depth ethnographic interviews. The
      results show that the respondents' perceptions were that their socializing agents
      and socializing environment emphasized athletics above other roles, other
      talents, and the development of other skills.

PMID- 21174873
TI  - An Afrocentric approach to building cultural relevance in social work research.
AB  - Social work researchers who identify and define social problems run the risk of
      leaving their social fingerprints on such problems, as well as their favored
      solutions to them. As a result, the direction of the research agenda is driven by
      the focus of the research problem formulation, instead of the cultural relevance.
      The purpose of this article is to offer guiding principles for integrating
      cultural relevance into the social work research process. The authors offer
      definitions of cultural relevance, a rationale for using cultural relevance in
      social work research, a framework for constructing cultural relevance in the
      process of research problem formulation, and an example of how this framework
      applies within the context of HIV prevention education in the African American
      community.

PMID- 21174874
TI  - Rebuilding the park: the impact of Hurricane Katrina on a black middle-class
      neighborhood.
AB  - The devastation of Hurricane Katrina unveiled the legacy of racial and class
      stratification in New Orleans, Louisiana. Much of the Katrina-related research
      has focused primarily on how poor Black neighborhoods were disproportionately
      affected by the disaster. While this body of research makes valid claims, there
      has been very little research that examines how Black middle-class residents in
      New Orleans were impacted by Hurricane Katrina. This study examines how residents
      in Pontchartrain Park, a Black middle-class neighborhood, are responding to the
      disaster. The author uses in-depth interviews, ethnographic observations, and
      archival data to examine the barriers that residents are facing in the recovery
      process. She argues that the experiences of the Black middle class also have
      implications for the connectedness of race and class. The challenges discussed
      within the article are linked to a history of racial stratification.

PMID- 21174876
TI  - Socio-cultural aspects of the high masculinity ratio in India.
AB  - The paper aims to explicate those factors accountable for the continuing
      imbalance in the sex ratio and its further masculinization over the whole of the
      20th century. Here it is contended that the traditional practice of female
      infanticide and the current practice of female foeticide in the contemporary
      period, especially in the north-west and Hindi-speaking states, have
      significantly contributed to the high masculinity ratio in India. In addition,
      increasingly higher survival ratios of male children, particularly from the 1951
      census onward, have been the prime reason for a declining proportion of females
      in the Indian population. As the Indian value system has been imbued with a
      relatively higher preference for sons, improvements in health facilities have
      benefited males more than females, giving rise to a highly imbalanced sex ratio
      in the country. This scenario, however, has steadily tended to alter in favour of
      greater balance in sex ratio.

PMID- 21174875
TI  - Understanding the occurrence of interracial marriage in the United States through
      differential assimilation.
AB  - American society is undergoing unprecedented cultural changes in the 21st
      century. This social transformation began with the civil rights movement in the
      1960s. As the United States becomes more diverse, both racially and ethnically,
      equal access to a variety of social institutions and organizations becomes more
      challenging. With respect to marriage, popular media continually report the
      blurring of boundaries between racial and ethnic groups. As a result, there has
      been a tremendous increase in interracial dating and marriage over the past
      several decades. There are considerable differences between the occurrence of
      interracial dating and interracial marriage. Data suggest that there is a much
      higher level of interracial dating in comparison to interracial marriage. This
      research effort focuses on trends in interracial marriages in the United States
      between 1980 and 2006. Information from the U.S. Census Bureau was used to
      analyze changes in the number and frequency of interracial marriages in American
      society over a 22-year time frame. Differential assimilation is employed for
      understanding interracial marriage trends and distinguishing important
      statistical differences between marriages with a Black spouse and those
      interracial marriages not involving a Black spouse. This exploration provides
      important empirical findings for assessing the progress of assimilation in
      America.

PMID- 21174877
TI  - National Rural Employment Guarantee Scheme, poverty and prices in rural India.
AB  - The objective of this analysis is mainly to construct an intuitive measure of the
      performance of the National Rural Employment Guarantee Scheme (NREGS) in India.
      The focus is on divergence between demand and supply at the district level. Some
      related issues addressed are: (i) whether the gap between demand and supply
      responds to poverty; and (ii) whether recent hikes in NREGS wages are
      inflationary. Our analysis confirms responsiveness of the positive gap between
      demand and supply to poverty. Also, apprehensions expressed about the
      inflationary potential of recent hikes in NREGS wages have been confirmed. More
      importantly, higher NREGS wages are likely to undermine self-selection of the
      poor in it.

PMID- 21174878
TI  - Microfinance and poverty reduction: evidence from a village study in Bangladesh.
AB  - To evaluate the competing claims on the impact of microfinance programs on
      multidimensional poverty, a village study in Bangladesh was conducted where three
      microfinance programs had been operating for more than five years. The study
      found that microfinance has resulted in a moderate reduction in the poverty of
      borrowers, as measured by a variety of socio-economic indicators, but has not
      reached many of the poorest in the village. To make microfinance a more effective
      means of poverty reduction other services such as skills training, technological
      support, education and health related strategies should be included with
      microfinance.

PMID- 21174879
TI  - Moving up the ladder or stuck on the bottom rung? Homeownership as a solution to
      poverty in urban South Africa.
AB  - In the global South, policies providing property titles to low-income households
      are increasingly implemented as a solution to poverty. Integrating poor
      households into the capitalist economy using state-subsidized homeownership is
      intended to provide poor people with an asset that can be used in a productive
      manner. In this article the South African "housing subsidy system" is assessed
      using quantitative and qualitative data from in-depth research in a state
      subsidized housing settlement in the city of Cape Town. The findings show that
      while state-subsidized property ownership provides long-term shelter and tenure
      security to low-income households, houses have mixed value as a financial asset.
      Although state-subsidized houses in South Africa are a financially tradable
      asset, transaction values are too low for low-income vendors to reach the next
      rung on the housing ladder, the township market. Furthermore, low-income
      homeowners are reticent to use their (typically primary) asset as collateral
      security for credit, and thus property ownership is not providing the financial
      returns that titling theories assume.

PMID- 21174880
TI  - The next stage of evolution of workplace wellness: a world economic forum/World
      Health Organization collaboration.

PMID- 21174881
TI  - The impact of conditional cash transfers on marriage and divorce.
AB  - A growing number of less-developed countries have introduced conditional cash
      transfer programs in which funds are targeted to women. Economic models of the
      family suggest that these transfer programs may lead to marital turnover among
      program beneficiaries. Data from the experimental evaluation of the PROGRESA
      program in Mexico is used to provide new evidence on the short-run impacts of
      targeted transfers on couples' union dissolution and individuals' new union
      formation decisions. We find that, although the overall share of women in union
      does not change as a result of the program, marital turnover increases. Intact
      families eligible for the transfers experienced a modest (0.32 percentage points)
      increase in separation rates, with most of the effect concentrated among young
      and relatively educated women households. In contrast, young single women with
      low educational attainment levels experienced a substantial increase in new union
      formation rates. The marital transition patterns are consistent with the
      workhorse economic model of the marriage market-individuals with the greatest
      prospects to start new unions and those who may become more attractive in the
      marriage market are more likely to transition out of existing relationships and
      form new ones.

PMID- 21174882
TI  - Preschool and maternal labor market outcomes: evidence from a regression
      discontinuity Design.
AB  - In developing countries, employment rates for mothers with young children are
      relatively low. This study analyzes how maternal labor market outcomes in
      Argentina are affected by the preschool attendance of their children. Using
      pooled household surveys, we show that 4-year-olds with birthdays on June 30 have
      sharply higher probabilities of preschool attendance than children born on July
      1, given enrollment-age rules. Regression-discontinuity estimates using this
      variation suggest that preschool attendance of the youngest child in the
      household increases the probability of full-time employment and weekly hours of
      maternal employment. We find no effect of preschool attendance on maternal labor
      outcomes for children who are not the youngest in the household.

PMID- 21174883
TI  - Is child labor harmful? The impact of working earlier in life on adult earnings.
AB  - This paper explores the question: is working as a child harmful to an individual
      in terms of adult outcomes in earnings? Although this is an extremely important
      question, little is known about the effect of child labor on adult outcomes.
      Estimations of an instrumental variables earnings model on data from Brazil show
      that child labor has a large negative impact on adult earnings for male children
      even when controlling for schooling and that the negative impact of starting to
      work as a child reverses at around ages 12-14.

PMID- 21174884
TI  - Targeting cyclone relief within the village: kinship, sharing, and capture.
AB  - This article investigates the targeting of cyclone relief within villages in
      Fiji. It focuses on how relief allocation is linked with informal risk sharing
      and elite capture, both of which are directly related to kinship. The results are
      as follows. First, food aid is initially targeted toward kin groups according to
      their aggregate shocks and then shared among group members. Right after the
      cyclone, when aid is scarce, households with damage to their housing and with
      greater crop damage are allocated less aid within the group. Instead, they
      receive greater net private transfers in other forms, especially in labor
      sharing. Consistent patterns are found in village, cropping, and housing
      rehabilitations. Second, there is no elite capture of food aid in the kin group,
      and instead, traditional kin leaders share food with others; however, non-kin
      based community leaders capture aid when it is allocated across kin groups.
      Third, distinct from food aid demanded by all, tarpaulins demanded by victims
      only strongly target individual housing damage at the village level-not the kin
      group-independent of social status. As with food aid, victims with greater crop
      damage are given a lower priority. Implications for relief policies are
      discussed.

PMID- 21174885
TI  - Answer quiz vol 11 no. 4. Destructive arthropathy of the shoulder in a man.
      Diagnosis: Charcot neuroarthropathy complicated with hydroxyapatite arthropathy.

PMID- 21174886
TI  - The rights of a Florida wife: slavery, U.S. expansion, and married women's
      property law.
AB  - Civil law rules were adopted in Florida that granted married women property
      rights long before legal reforms occurred in northern states. This article
      analyzes white wives' property and law in Florida between 1820 and 1860.
      Initially, married women's property rights were inadvertently protected by treaty
      law and limited to women who married before 1818. Wives' right to own separate
      property in Florida was subsequently reconfirmed in statute and extended to
      include later marriages. In contrast, nonwhites generally lost the rights and
      property they had enjoyed under Spain's civil law in the same period. This
      contrast reveals that in Florida (and other southern borderlands) it was not
      concern for women, or simply legal precedent, but the desire to incorporate new
      territory and expand slavery that influenced the development of marital property
      law. This challenges previous histories, which have excluded the earlier acts in
      the Southern borderlands and emphasized those passed in the Northeast beginning
      in the late 1840s. While those later acts were influenced by the early woman's
      rights movement and by concern for families reduced to poverty during the rise of
      market capitalism, this case study indicates that expansion of United States
      territory and slavery were responsible for the earlier married women's property
      rights in southern borderland territories such as Florida.

PMID- 21174887
TI  - The "cradle of glass": incubators for infants in late nineteenth-century France.
AB  - This article examines the development of the incubator for premature infants in
      fin-de-siecle France. During a period of widespread anxiety in France regarding
      infant mortality and its implications for population growth, physicians in Paris
      developed and widely promoted the lifesaving technology. This article explores
      the ways in which the incubator reflected new scientific and symbolic approaches
      to creating hygienic spaces as well as how it reflected new scientific and
      symbolic approaches to the traditionally feminine project of infant care. By
      creating such an isolating and protective milieu around premature infants-an
      entirely new population of patients-the incubator, I argue, heralded a
      renegotiation of the boundary between motherhood and medical authority.

PMID- 21174888
TI  - Claims to protection: the rise and fall of feminist abolitionism in the League of
      Nations' Committee on the Traffic in Women and Children, 1919-1936.
AB  - This article examines the League of Nations Advisory Committee on the Trafficking
      of Women and Children (CTW) to assess the impact of international feminists on
      the interwar anti-sex trafficking movement. It argues that women who were firmly
      embedded in the transnational and international women's rights movement built a
      coalition on the CTW to ensure the prominence of the feminist abolitionist
      position of sex trafficking in the 1920s. This position was defined by calls for
      equal standards of morality between the sexes, resistance to laws that treated
      prostitutes as a group and infringed on their human rights, and unwavering
      demands for the abolition of state-regulated prostitution. Changes in the
      personnel and bureaucratic structure of the CTW and the rising tide of
      nationalism served to undermine the feminist abolitionists' position in the
      League in the 1930s.

PMID- 21174889
TI  - Pink truck ads: second-wave feminism and gendered marketing.
AB  - Second-wave feminist media had a contentious relationship with corporate
      advertisers. This article uses automotive advertisements to explore the role of
      gender, class, and race in the construction of consumer markets from the 1970s
      through the 1980s. It analyzes the struggle of Gloria Steinem and other liberal
      feminists to navigate the terrain between the women's movement and corporate
      advertisers. The increased economic power of women, stemming from the Equal
      Credit Opportunity Act as well as broader social and political shifts,
      facilitated their efforts. In the 1980s, automobiles continued to be marketed to
      women, albeit through "feminine" imagery conforming to the era's dominant trends.

PMID- 21174890
TI  - Women stereotypes in Shi Zhecun's short stories.
AB  - This article analyses the representation of women in two 1933 short story
      collections by Shi Zhecun: An Evening of Spring Rain and Exemplary Conduct of
      Virtuous Women. It discusses how the New Woman image was a site of contestation
      in Republican China, and argues that Shi Zhecun's short stories contain four
      basic stereotypes: the enigmatic woman, the estranged wife, the prostitute, and
      the inhibited woman. Using these narratives of women and how they were perceived
      by men, Shi Zhecun deconstructed the New Woman image by subverting the various
      ways modernity was projected onto women.

PMID- 21174891
TI  - A model for the interdisciplinary design process.

PMID- 21174892
TI  - Re: Lessons from evidence-based medicine: what healthcare designers can learn
      from the medical field.

PMID- 21174893
TI  - The impact of gentrification on ethnic neighbourhoods in Toronto: a case study of
      little Portugal.
AB  - Despite extensive literature on the nature and impact of gentrification, there
      has been little consideration of the effects of gentrification on ethnic
      neighbourhoods. This study evaluates the negative and positive effects of
      gentrification on the Portuguese in west central Toronto. Details concerning the
      settlement patterns of the Portuguese, the characteristics of Portuguese
      residents and patterns of gentrification in inner-city Toronto were obtained from
      census data. Evaluations of neighbourhood change and attitudes of the residents
      towards gentrification were obtained from key informant and focus group
      interviews. The results suggest considerable ambivalence among the respondents,
      but most agreed that the long-term viability of Little Portugal as an immigrant
      reception area with a good supply of low-cost housing is in doubt.

PMID- 21174894
TI  - Vauxhall's post-industrial pleasure gardens: "death wish" and hedonism in 21st
      century London.
AB  - In recent years Vauxhall in south London has been transformed and rebranded as an
      urban leisure zone for gay men. Disused railway arches and warehouses have been
      converted into nightclubs and a significant night-time economy has developed
      rivalling Soho's existing gay village. However, with its commodified forms of
      public sex and high levels of recreational drug use, Vauxhall's club scene looks
      rather different from the British gay villages of the 1990s. This article
      examines how the area's nightlife entrepreneurs have capitalised on the recent
      liberalisation of licensing laws while drawing on the historical associations
      with the Vauxhall Pleasure Gardens (1660-1859) in attempts to market the area as
      a site of embedded hedonism. Overall, the aesthetic and cultural themes of
      Vauxhall's club scene seem to contradict earlier assumptions about the
      desexualisation and sanitisation of contemporary gay culture.

PMID- 21174895
TI  - The impact of transit-oriented development on housing prices in San Diego, CA.
AB  - This research measures the influence of transit-oriented development (TOD) on the
      San Diego, CA, condominium market. Many view TOD as a key element in creating a
      less auto dependent and more sustainable transport system. Price premiums
      indicate a potential for a market-driven expansion of TOD inventory. A hedonic
      price model is estimated to isolate statistically the effect of TOD. This
      includes interaction terms between station distance and various measures of
      pedestrian orientation. The resulting model shows that station proximity has a
      significantly stronger impact when coupled with a pedestrian-oriented
      environment. Conversely, station area condominiums in more auto-oriented
      environments may sell at a discount. This indicates that TOD has a synergistic
      value greater than the sum of its parts. It also implies a healthy demand for
      more TOD housing in San Diego.

PMID- 21174896
TI  - An architect's response.

PMID- 21174897
TI  - Retrofitting the suburbs to increase walking: evidence from a land-use-travel
      study.
AB  - This paper reports results from a detailed travel diary survey of 2125 residents
      in the South Bay area of Los Angeles County - a mature, auto-oriented suburban
      region. Study areas were divided into four centres, typical of compact
      development or smart growth, and four linear, auto-oriented corridors. Results
      show substantial variation in the amount of walking across study areas. Trips are
      shorter and more likely to be via walking in centres. A key to the centres'
      increased walking travel is the concentration of local shopping and service
      destinations in a commercial core. Yet the amount of business concentration that
      is associated with highly pedestrian-oriented neighbourhoods is from three to
      four times as large as what can be supported by the local resident base,
      suggesting that pedestrian-oriented neighbourhoods necessarily import shopping
      trips, and hence driving trips, from larger surrounding catchment areas. The
      results suggest both land use and mobility strategies that can be appropriate for
      suburban regions.

PMID- 21174898
TI  - Where is the cafe? The challenge of making retail uses viable in mixed-use
      suburban developments.
AB  - Contemporary planners see mixing residential, retail and other compatible uses as
      an essential planning principle. This paper explores the challenges that
      planners, developers and municipal councillors encounter in trying to implement
      retail uses as part of the mix in suburban areas in three Canadian cities. The
      study finds that planners employ evolutionary theories of urban development to
      naturalise their normative visions of walkable and sociable communities. By
      contrast, developers point to consumer behaviour to explain why planners' ideas
      on mix do not work. In a society where people shop at big-box outlets, making the
      local cafe or pub commercially viable proves increasingly challenging.

PMID- 21174899
TI  - Meeting highlights: Endocrine Society, San Diego, California, June 19-22, 2010.

PMID- 21174900
TI  - Highlights from the Second European Workshop on Growth Plate Research 2010.

PMID- 21174901
TI  - [Cochrane review about the effect of acamprosate].

PMID- 21174902
TI  - [Autopsy of the Hotel de Ville massacre, 4 July 1652: Paris and the "Fronde des
      Princes"].

PMID- 21174903
TI  - [The power of blood: from mestizo to the idea of race mixture in Spanish colonial
      America].

PMID- 21174904
TI  - Evidence-based design.

PMID- 21174905
TI  - Lean construction.

PMID- 21174906
TI  - The extent and nature of dental fear and phobia in Australia.
AB  - BACKGROUND: For the general dental practitioner, fearful patients are harder and
      more stressful to treat and are most likely to attend irregularly. This study
      presents updated and refined dental fear and phobia prevalence estimates in
      Australia as well as information on the nature of dental fear and phobia.
      METHODS: A total of 1084 Australian adults (response rate = 71.7%) completed a
      mailed questionnaire. The survey contained four measures of dental fear and
      phobia, as well as questions regarding potentially anxiety-eliciting dental
      stimuli and past aversive dental experiences. RESULTS: The prevalence of high
      dental fear ranged from 7.8% to 18.8%, and more incapacitating dental phobia from
      0.9% to 5.4%, depending upon the scale, cut-point and specific criteria used.
      Dental phobia was significantly associated with blood-injection-injury (BII)
      concerns. The cost of dental treatment was endorsed as the most anxiety-eliciting
      dental situation (64.5%), followed by fear of needles/injections (46.0%) and
      painful or uncomfortable procedures (42.9%). Anxiety-eliciting stimuli and the
      type of aversive dental experiences varied significantly by gender, age, income,
      education, language spoken at home and dental visiting frequency. CONCLUSIONS:
      High dental fear and dental phobia are common in Australia although prevalence
      estimates are highly dependent on both the scale and cut-points used.

PMID- 21174907
TI  - Oral cavity squamous cell carcinoma survival by biopsy type: a cancer registry
      study.
AB  - BACKGROUND: Biopsy of a suspected oral squamous cell carcinoma (SCC) is important
      for diagnosis. Concerns have been raised about the potential for tumour spread by
      incisional biopsy techniques. This study aimed to investigate the five-year
      survival and recurrence of oral SCC after incisional and excisional biopsy in
      total population data available from the Western Australian Cancer Registry
      (WACR). METHODS: Total population data from the WACR, comprising all primary oral
      SCC cases diagnosed between 1990 and 1999, were examined. Information extracted
      included date of birth, gender, biopsy date, biopsy type, disease stage (TNM
      classification), disease site, date of recurrence and date of death. Records were
      excluded if the diagnosis was fine needle aspiration based, was not that of oral
      SCC and if a history was noted of another malignant neoplasm. Incisional and
      excisional biopsy cases were compared for five-year survival, adjusting for
      disease stage. RESULTS: No association was found between biopsy type and five
      year survival or recurrence amongst individuals with Stage I or II disease.
      CONCLUSIONS: In this study, biopsy type was not associated with survival of oral
      SCC patients with Stage I or II disease, adding to the evidence that incisional
      biopsy of oral SCC can be a safe procedure.

PMID- 21174908
TI  - Intermountain Healthcare, to improve and enhance the healthcare environments and
      safety of all their major hospital facilities.

PMID- 21174909
TI  - Immunoexpression of matrix metalloproteinase-2 and matrix metalloproteinase-9 in
      the metastasis of squamous cell carcinoma of the human tongue.
AB  - BACKGROUND: Squamous cell carcinoma of the tongue has frequent lymph node
      metastases and poor prognosis. Matrix metalloproteinase-2 (MMP-2) and matrix
      metalloproteinase-9 (MMP-9) are reported to degrade basement
      membrane,facilitating invasion and metastasis. This study determined the
      expression of MMP-2/MMP-9 in primary tongue cancer with or without cervical
      metastases and analysed the significance of such expression in relation to the
      presence or absence of metastases. METHODS: Expressions of MMP-2/MMP-9 were
      detected by immunohistochemistry in 10 specimens of normal oral mucosa, 20 lymph
      node-negative tongue cancers, 41 lymph node-positive tongue cancers and their
      metastasized tumours in cervical lymph nodes. RESULTS: MMP-2/MMP-9 expression was
      seldom found in normal epithelium. In lymph node-negative tongue cancer, 45% and
      40% of these primary tumours were positively stained for MMP-2/MMP-9,
      respectively. Importantly, in lymph node-positive tongue cancer, 71% and 79% of
      these primary tumours were positive for MMP-2/MMP-9, respectively. Overexpression
      of MMP-2/MMP-9 was present in the metastatic lymph nodes. CONCLUSIONS: Our
      results imply that MMP-2 and/or MMP-9 play an important role in invasion and
      metastasis in tongue cancer, and that analysis of MMP expression and/or activity
      in primary tumours may have a predictive value for the actual or potential
      presence of cervical metastases.

PMID- 21174910
TI  - Impact of the storage temperature on human plasma proteomic analysis:
      implications for the use of human plasma collections in research.
AB  - PURPOSE: To analyze the impact of storage temperature on the 2D-DIGE profile of
      human plasma. EXPERIMENTAL DESIGN: 2D-DIGE and MS were used to identify the
      differences in the proteomic profiles of aliquots of eight human plasma samples
      stored at either - 30 or - 80 degrees C for 18 months. RESULTS: After the
      depletion of albumin and IgG, 2D-DIGE identified four spots significantly and
      reproducibly increased, and five spots that were decreased, in samples stored at 
      30 degrees C compared with those stored at - 80 degrees C. These nine spots were
      manually excised, digested ingel and analyzed by MALDI-TOF/TOF. MASCOT database
      search using the PMF spectra allowed the identification of the proteins present
      in eight of the nine spots. All the spots corresponded to the complement C3
      precursor protein. CONCLUSIONS AND CLINICAL RELEVANCE: Our present results
      indicate that plasma collections stored at -30 degrees C, and not only those
      stored at - 80 degrees C, may be used for 2D-DIGE analyses of albumin-and IgG
      depleted human plasma without loosing the essential information about highly
      abundant proteins. This finding expands the applicability of 2D-DIGE to the study
      of human disease by permitting the analysis of human plasma samples stored at
      temperatures between - 30 and - 80 degrees C.

PMID- 21174912
TI  - [From peasant daughter to samurai wife: the letters of Yoshino Michi].

PMID- 21174913
TI  - [Socialism and social protection - a tautology? Child abandonment in the USSR,
      1917-31].

PMID- 21174915
TI  - [Mechanizing writing and picturing speech: utopias in the office world and
      histories of gender and techniques].

PMID- 21174916
TI  - Amazing Grace: twentieth-century guardian of the Seagrave Missionary legacy.

PMID- 21174917
TI  - Clara Chase Leach, M.D.: beloved physician.

PMID- 21174918
TI  - Lena Adell Benjamin: missionary gold medallist.

PMID- 21174919
TI  - Dorothy Kinney Chambers: a most valiant woman.

PMID- 21174920
TI  - Preface. Insects comprise over 50% of all life on Earth.

PMID- 21174921
TI  - Effect of preoperative prednisolone on clinical postoperative symptoms after
      surgical extractions of mandibular third molars.
AB  - BACKGROUND: This study compared postoperative symptoms in patients treated
      preoperatively with a single dose of <=20 mg oral steroid during third molar
      surgery. METHODS: A total of 450 patients were categorized randomly into three
      groups containing 150 patients each. Patients were in their second or third
      decade and had no specific medical history and findings involving infections of
      the mandibular third molar area. Two groups received preoperative steroids orally
      one hour before the operation; one group received 10 mg prednisolone and the
      other received 20 mg. No steroids were administered to the control group.
      Patients were asked to report by questionnaire any changes in postoperative
      symptoms, such as pain, facial oedema, or gastrointestinal disorders, and in
      masticatory disorders, trismus, or swallowing discomfort. They reported daily
      from days 1 to 6 post-extraction by evaluating their experience over the
      preceding 24 hours. RESULTS: A single preoperative oral administration of <=20 mg
      prednisolone had no significant effect on postoperative symptoms of pain, facial
      oedema, or gastrointestinal upset, or on masticatory symptoms, trismus, or
      swallowing discomfort in mandibular third molar surgery. CONCLUSIONS: A single
      oral dose of <=20 mg prednisolone before third molar extraction may not be
      helpful for the relief of postoperative symptoms.

PMID- 21174922
TI  - Dental caries experience among young Australian adults.

PMID- 21174923
TI  - Podcast transcripts from the Cochrane Nursing Care Field.

PMID- 21174924
TI  - Dr. Mary Ella Kirby Berry of Assam: servant in her heart's true home.

PMID- 21174925
TI  - [To build a better society: the political debate on housing, 1945-55].

PMID- 21174926
TI  - The Dublin parishes and the poor: 1660-1740.

PMID- 21174927
TI  - [Pulmonary tuberculosis].

PMID- 21174928
TI  - [The infant with recurrent wheezing and inhaled corticosteroids therapy].

PMID- 21174929
TI  - A synopsis of the field of health education in Malawi.

PMID- 21174930
TI  - Variation of semen parameters in healthy medical students due to exam stress.
AB  - AIM: This study was aimed at investigating semen parameters that vary most in
      samples of healthy donors undergoing stressful examination period. METHODS:
      Samples were left to liquefy in an incubator at 37 degrees C, 5% CO2 for 30
      minutes before volume was measured. Concentration and motility parameters were
      measured by means of computer assisted semen analysis (CASA) using Sperm Class
      Analyzer (Microptic S.L, Madrid, Spain). RESULTS: Sperm concentration was
      significantly decreased in samples donated close to the exam period as well as
      samples donated during the exam period when compared to samples donated at the
      beginning of the semester. CONCLUSION: Stress levels of donors might prove to be
      clinically relevant and important when designing experiment protocols.

PMID- 21174931
TI  - Women's groups' perceptions of neonatal and infant health problems in rural
      Malawi.
AB  - AIMS: To present the perceptions of women in rural Malawi regarding the health
      problems affecting neonates and infants and to explore the relevance of these
      perceptions for child health policy and strategy in Malawi. METHODS: Women's
      groups in Mchinji district identified newborn and infant health problems (204
      groups, 3484 women), prioritised problems they considered most important (204
      groups, 3338 women) and recorded these problems on monitoring forms. Qualitative
      data was obtained through 6 focus-group discussions with the women's groups and
      22 interviews with individuals living in women's group communities but not
      attending groups. RESULTS: Women in Malawi do not define the neonatal period
      according to any epidemiological definition. In order of importance they
      identified and prioritised the following problems for newborns and infants:
      diarrhoea, infection, preterm birth, tetanus, malaria, asphyxia, respiratory
      tract infection, hypothermia, jaundice, convulsions and malnutrition. CONCLUSION:
      This study suggests that women in rural Malawi collectively have a developed
      understanding of neonatal and infant health problems. This makes a strong
      argument for the involvement of lay people in policy and strategy development and
      also suggests that this capacity, harnessed and strengthened through community
      mobilisation approaches, has the potential to improve neonatal and infant health
      and reduce mortality.

PMID- 21174932
TI  - Open tibia fractures in HIV positive patients.
AB  - Open tibia fractures are common injuries, particularly in developing
      countries.Pedestrian or bicycle to motor car contact is the most common
      mechanism. These injuries result in high morbidity and often long-term
      disability. HIV infection complicates open fractures by raising the incidence of
      infectionin the open wound (5 of 7 patients in our series). This risk may be
      compounded if internal fixation techniques are used (5 of 12 HIV patients with
      internal fixation of any open fracture). There is also a suggestion that HIV may
      delay bone union (4 of 7 patients united at 6 months). External fixation offers
      an alternative method of fracture stabilisation. It avoids the risks associated
      with putting metal-ware in the wound, but creates a new issue of pin track
      sepsis. We found that pin track infection was more common in patients with HIV,
      but the rate at which pins required removal was 7%. We consider external fixation
      to be a lower-risk strategy than internal fixation in such patients but open
      fracture wound sepsis remains a problem. We have not yet demonstrated a
      difference in severity or frequency of complications in patients of low CD4
      count, but logically one expects septic complications to increase as CD4 count
      falls. Antiretroviral medication decreases viral load and elevates the CD4 count.
      Research is underway regarding potential effectiveness of such drugs in reducing
      wound and fracture healing complications. Above all, meticulous and timely all
      round care is required to achieve satisfactory results in immune-compromised
      patients. This includes, debridement, bony stability, and soft-tissue
      reconstruction.

PMID- 21174934
TI  - Ward round-- non-resolving pleural effusion in a patient with HIV infection.

PMID- 21174933
TI  - Similar cellular responses after treatment with either praziquantel or
      oxamniquine in Schistosoma mansoni infection.
AB  - The effect of treatment with either oxamniquine or praziquantel on S.mansoni
      specific IFN-gamma, IL-4, IL-5 and IL-10 was compared on PBMC which were
      collected pretreatment, 6 and 18 weeks post treatment. Using sandwich ELISA on
      the supernatants harvested from the PBMC stimulation by crude S. mansoni SEA and
      SWAP antigens after 5 days the levels of PBMC proliferation and cytokine
      production were similar according to treatment with either praziquantel or
      oxamniquine. Before treatment, infected groups showed low ratios, of IL-4:IFN
      gamma, IL-5:IFNgamma and IL-10:IFN-gamma, indicating that IFN-gamma was high in
      the infected individuals. The general increase in immuno-modulation was observed
      post-treatment with elevated immune reactivity and cytokine production in both
      treatment groups. Treatment induced significant increases in levels of IL-4 (p <
      0.05), IL-5 (p < 0.0001) and IL-10 (p < 0.05) cytokines 6 and 18 weeks after
      treatment. There were no significant differences in the increase in IL-4, IL-5
      and IL-10 between children treated with praziquantel or oxamniquine. Pre
      treatment IFN-gamma and IL-5 levels were positively correlated with infection (p
      < 0.001), while post treatment IL-4 cytokine levels were negatively correlated
      with baseline infection status (p < 0.001). The results suggest that treatment
      induced immune responses are similar for both common anti-schistosome drugs
      praziquantel or oxamniquine having similar and immunizing effect.

PMID- 21174935
TI  - Opinions on abortion as a viable way of improving reproductive health.

PMID- 21174936
TI  - Light and electron microscopy study of the pecten oculi of the jungle crow
      (Corvus macrorhynchos).
AB  - In this study, the pecten oculi of a diurnally active bird, the Japanese jungle
      crow (Corvus macrorhynchos), was examined using light and electron microscopy. In
      this species, the pecten consisted of 24-25 highly vascularized pleats held
      together apically by a heavily pigmented 'bridge' and projected freely into the
      vitreous body in the ventral part of the eye cup. Ascending and descending blood
      vessels of varying caliber, together with a profuse network of capillaries,
      essentially constituted the vascular framework of the pecten. A distinct
      distribution of melanosomes was discernible on the pecten, the concentration
      being highest at its apical end, moderate at the crest of the pleats and lowest
      at the basal and lateral margins. Overlying and within the vascular network, a
      close association between blood vessels and melanocytes was evident. It is
      conjectured that such an association may have evolved to augment the structural
      reinforcement of this nutritive organ in order to keep it firmly erectile within
      the gel-like vitreous. Such erectility may be an essential prerequisite for its
      optimal functioning as well as in its overt use as a protective shield against
      the effects of ultraviolet light, which otherwise might lead to damage of the
      pectineal vessels.

PMID- 21174937
TI  - Comparison of maxillary and mandibular dental arch forms by studying Fourier
      series developed from mathematically estimated dentitions.
AB  - We conducted a Fourier analysis on data obtained using correlation and principal
      component analyses of parallel-standardized dental study models; both maxillary
      and mandibular dental arches were predominantly round square in shape. The
      present study compared and determined the contribution ratio and reproducible
      coefficients of amplitudes (factors affecting dental arch forms), and
      demonstrated that the 1st to 4th and the 1st to 6th Fourier harmonics reproduced
      maxillary and mandibular dental arch forms, respectively. The correlation
      analyses of the constant term and amplitudes demonstrated that significant
      differences in the 2nd harmonic amplitude was strongly correlated with the
      curvature of anterior teeth and the length-to-width ratio in maxillary
      dentitions. By comparison of the constant term and amplitudes between different
      arch types, we did not observe significant differences in the constant term and
      the 1st amplitude of maxillary dentitions and in constant term and all amplitudes
      of mandibular dentitions. Nevertheless, the study revealed high contribution
      ratios of the 1st (in mandibular dentitions) and the 2nd (in maxillary
      dentitions) amplitudes essentially affecting the reproducibility of arch forms.
      The 1st amplitudes demonstrated a bow-like arrangement of all arch types, while
      the 2nd amplitudes adjusted the anterior-teeth curvature and in particular
      demonstrated the length-to-width ratio of maxillary dentitions. The 3rd and the
      4th amplitudes were also determinants of the anterior-teeth curvature of
      maxillary dentitions. The 6th amplitude was necessary for reproduction, but
      showed no difference between varying mandibular dental arch types. Collectively,
      we conclude that the establishment of a Fourier series significantly reproduced
      maxillary but not mandibular dental arch forms.

PMID- 21174938
TI  - Discussion of clinical anatomy of the lingual nerves.
AB  - The tongue has various functions, such as gustation, pronunciation, mastication,
      and deglutition. The nerve fibers are complexly intermingled, and communications
      between the lingual nerve and the hypoglossal nerve have been reported. Fifteen
      Japanese heads (30 sides) donated to the 2nd-year students dissection course at
      the Nippon Dental University School of Life Dentistry, Niigata, were studied with
      regard to the following aspects: 1. relation of the bifurcation between the
      lingual and the inferior alveolar nerves close to the oval foramen; 2. distance
      between the oral foramen and the bifurcation of the lingual and inferior alveolar
      nerves; and 3. communication between the lingual and hypoglossal nerves. Three
      types of bifurcation were observed. The standard bifurcation was observed in 21
      cases (70.1%). A high bifurcation was observed in 5 cases (16.6%), and a
      communicating bifurcation was observed in 4 cases (13.3%). The average distance
      between the oval foramen and the bifurcation of the lingual and inferior alveolar
      nerves was 8.7 +/- 4.2 mm (minimum: 0 mm/maximum: 14 mm). An anterior-type
      communication between the lingual and hypoglossal nerves was observed in 8 cases
      (26.6%), a posterior-type was observed in 17 cases (56.7%), and no communication
      was observed in 5 cases (17.7%).

PMID- 21174939
TI  - Histological development of human testicular cords from 70 to 90 days of
      gestation.
AB  - The development of the testicular cord structure was investigated in 4 human
      fetuses between 70 and 90 days of gestation, in which the testicular cords are
      differentiating into the seminiferous tubules. Histological examinations were
      performed using stains with haematoxylin-eosin (HE), Masson's trichrome (MT),
      periodic acid schiff (PAS), anti-proliferating cell nuclear antigen (PCNA)
      monoclonal antibodies, and TUNEL methods. It was found that the testicular cords
      structures were indefinitely observed in HE-stained sections of four fetuses.
      However, the basement membranes of the testicular cord were clearly stained with
      MT, showing the tubular structure. Furthermore, cells in the testicular cords
      were positive with PAS, but the interstitial tissues outside the testicular cords
      were negative. PCNA-positive cells were detected not only inside but also outside
      the testicular cords, however, TUNEL positive cells are not detected throughout
      all testicular tissues.

PMID- 21174940
TI  - Three-dimensional organization of the perivascular glial limiting membrane and
      its relationship with the vasculature: a scanning electron microscope study.
AB  - To examine the three-dimensional structure of the perivascular glial limiting
      membrane (Glm) and its relationship with the vasculature in rat/mouse cerebral
      cortices, serial ion-etched plastic sections were observed under the scanning
      electron microscope and their images were reconstructed. In the case of
      arterioles and venules close to the pial surface, cord-like principal processes
      predominantly formed the endfeet; whereas in the case of capillaries and venules,
      sheet-like secondary processes chiefly formed Glm. Moreover, it was found that
      several plate-like structures protruded from the basement membrane surrounding
      the arterioles to penetrate into the astrocytic somata. The perivascular Glm was
      formed by monolayers of astrocytic processes and/or somata irrespective of the
      types of blood vessel. However, the thickness of the perivascular Glm, varied
      greatly according to the type of blood vessel. The thickness of Glm decreased in
      the order of arterioles, venules and capillaries. The outer surface of the
      perivascular Glm was extremely irregular, and sheet-like processes arising from
      this Glm infiltrated into the surrounding neuropil.

PMID- 21174941
TI  - Observing the bony canal structure of the human maxillary sinus in Japanese
      cadavers using cone beam CT.
AB  - We observed the location of the posterior superior alveolar artery (PSAA) and
      nerve at the macroscopic level between the maxillary sinus (MS) and surrounding
      bone of the anterior region of the maxilla. This study was completed using cone
      beam computed tomography (CBCT) imaging of 19 human cadavers with 38 sides of
      Japanese origin (ranging in age from 59-94 years, mean 77.7 +/- 9.8 years) that
      were prepared for this study. The bony canal structure of the inner surface of
      the maxilla was clearly apparent in our results, and the bony canals were
      classified into three types according to the structure along the course of the
      PSAA: canal-like, ditch-shaped tunnel and fragmented, and the lest sides were
      undefined. Calcitonin gene-related peptide (CGRP)-positive fibers were identified
      along the PSAA in the bony canal of the maxilla by immunohistochemistry. The
      presence of the bony structure and CGRP-positive nerve fibers along the PSAA
      suggests that there is risk to the PSAA during surgery involving graft implant in
      the floor of the maxillary sinus.

PMID- 21174942
TI  - Evaluation of the blood and nerve supply patterns in the molar region of the
      maxillary sinus in Japanese cadavers.
AB  - The maxillary sinus (MS) in the maxilla bone is located near the orbit, the nasal
      cavity and the oral cavity; however, the positioning of the constituent bones is
      complex. The posterior superior alveolar branches of the maxillary artery and
      nerve are distributed in the lateral wall of the MS. The courses of these blood
      vessels and nerves are restricted by the morphology of the craniofacial bones,
      and the landmarks used in dental implant treatment of these courses mainly run
      along the lateral wall of the MS. In this study, 19 human cadavers with 34 sides
      of Japanese origin (ranging in age from 59-94 years, mean 77.7 +/- 9.8 years)
      were prepared for measurement of the MS, the superior alveolar artery and the
      infraorbital artery using cone beam computed tomography (CBCT). The posterior
      superior alveolar artery (PSAA) of the lateral wall of the MS can be classified
      into one of three groups based on the supply pattern. In the greatest number of
      cadavers, the PSAA ran mainly to the lateral surface of the zone between the
      superior border of the alveolar foramen and the inferior border of the MS (53.0%,
      18/34). In others, the PSAA ran to the zone between the infraorbital foramen and
      the superior border of the alveolar foramen (17.6%, 6/34); in a third group, the
      PSAA ran to the zone between the inferior border of the MS and the greater
      palatine foramen (23.5%, 8/34). The lest of two sides are spread out in this area
      (5.9%, 2/34). CBCT is the most accurate tool to evaluate important anatomical
      parameters, such as the distance of the blood supply, for the implant of grafts
      in the floor of the MS during surgical procedures.

PMID- 21174943
TI  - Masticatory function and cognitive function.
AB  - Recent studies have suggest that masticatory (chewing) function is useful for
      maintaining neurocognitive function in the elderly. For example, a reduced
      ability to masticate, such as that resulting from toothlessness or soft-diet
      feeding, causes learning and memory deficits in aged animals and pathologic
      changes in the hippocampus. In addition, occlusal disharmony impairs hippocampal
      memory processes via chronic stress, and induces similar hippocampal pathology.
      Chewing, however, rescues stress-induced suppression of long-term potentiation in
      the hippocampus and the stress-induced impairment of hippocampal-dependent
      learning. These findings strongly suggest a link between mastication and
      neurocognitive function.

PMID- 21174944
TI  - Reasonable classical concepts in human lower limb anatomy from the viewpoint of
      the primitive persistent sciatic artery and twisting human lower limb.
AB  - The main aim of this review is (1) to introduce the two previous studies we
      published human lower limb anatomy based on the conventional macroscopic
      anatomical [corrected] criteria with hazardous recognition of this description,
      (2) to activate the discussion whether the limb homology exists, and (3) to
      contribute to future study filling the gap between the gross anatomy and
      embryology. One of the topics we discussed was the human persistent sciatic
      artery. To date, numerous human cases of persistent sciatic artery have been
      reported in which the anomalous artery was present in the posterior compartment
      of the thigh alongside the sciatic nerve. As one of the important criteria for
      assessing the human primitive sciatic artery, its ventral arterial position with
      respect to the sciatic nerve is reasonable based on the initial positional
      relationship between ventral arterial and dorsal nervous systems and comparative
      anatomical findings. We also discuss ways of considering the topography of
      muscles of the lower limb and their innervations compared to those of the upper
      limb. We propose a schema of the complex anatomical characteristics of the lower
      limb based on the vertebrate body plan. According to this reasonable schema, the
      twisted anatomy of the lower limb can be understood more easily. These two main
      ideas discussed in this paper will be useful for further understanding of the
      anatomy of the lower limb and as a first step for future. We hope that the future
      study in lower limb will be further developed by both viewpoints of the classical
      gross anatomy and recent embryology.

PMID- 21174945
TI  - PKC plays a crucial roles in c-mpl gene expression in megakaryoblastic cells.
AB  - Thrombopoietin is the cytokine involved in megakaryopoiesis and its receptor (c
      Mpl) is considered to regulate development of megakaryocyte. In this research, to
      elucidate the underlying mechanisms of c-mpl gene expression in megakaryoblastic
      cells, we investigated the effect of a protein kinase C (PKC) on c-mpl promoter
      activity in a time-dependent manner. PKC is a member of a family of
      serine/threonine protein kinases in the cytosol involved in cell growth and
      differentiation. Phorbol 12-myristate 13-acetate (PMA) is known as PKC activator,
      significantly enhanced the c-mpl promoter activity and PKC inhibitor, 2
      methylpiperazine dihydrochloride (H-7) suppressed the up-regulation of PMA
      induced promoter activity and this effect decreased in a time-dependent manner.
      These results clearly suggest that in megakaryoblastic cells, PKC plays the
      crucial role in the initiation of up-regulation of PMA-induced c-mpl promoter
      activity.

PMID- 21174946
TI  - Structural insight to mutated Y116S transthyretin by molecular dynamics
      simulation.
AB  - Familial amyloidotic polyneuropathy (FAP) is strictly associated with point
      mutations of transthyretin (TTR) protein. The Tyr116-->Ser (Y116S) mutant TTR is
      an important amyloidogenic variant responsible for FAP. Structural dynamics of
      monomeric TR and its mutant (Y116S) may give some clue relating to amyloid
      formation. In this study, molecular dynamic simulation at 310 K has been
      performed on wild-type and mutant (Y116S) 'ITR monomer, which can provide the
      molecular insight of structural transition in the inner and outer strand of the
      protein. Results show that mutation in the H-strand (Tyr116-->Ser) leads to
      disruption of secondary structure and H-bonding pattern of some important parts
      of the inner DAGH-sheet of the protein. Especially, the residues T106, A108, L110
      of G-strand, S117 and T119 of H-strand are affected, which are involved in the
      binding of thyroxin hormone. This unfolding of mutant structure during dynamics
      may cause instability in the protein and thus induce amyloidgenesis.

PMID- 21174947
TI  - Molecular cloning, purification and characterization of thermostable beta-1,3-1,4
      glucanase from Bacillus subtilis A8-8.
AB  - A gene encoding a beta-1,3-1,4-glucanase (CelA) belonging to family 5 of
      glycoside hydrolases was cloned and sequenced from the Bacillus subtilis A8-8.
      The open-reading-frame of celA comprised 1499 base pairs and the enzyme was
      composed of 500 amino acids with a molecular mass of 55 kDa. The recombinant beta
      1,3-1,4 glucanase was purified by GST-fusion purification system. The pH and
      temperature optima of the enzyme were 8.0 and 60 degrees C, respectively. The
      enzyme was stable within pH 6.0-9.0. It was stable up to 60 degrees C and
      retained 30% of its original activity at 70 degrees C for 60 min. It hydrolyzed
      lichenan, CMC, xylan, laminarin, avicel and pNPC, but was inactive towards
      cellobiose. The enzyme activity was markedly activated by Co2+ and Mn2+, but was
      strongly inactivated by Fe3+. The truncated gene, devoid of cellulose-binding
      domain (CBD) showed 60% of activity and bound to avicel.

PMID- 21174948
TI  - Serum protein profiling to identify biomarkers for small renal cell carcinoma.
AB  - Diagnostic biomarkers for early detection of renal cell carcinoma (RCC) are in
      great need. In the present study, we compared the serum protein profiles of
      patients with small RCC to those of healthy individuals to identify the
      differentially expressed proteins with potential to serve as biomarkers. Serum
      samples were collected from 10 patients with small RCC and 10 healthy
      individuals. The serum protein expression profiles were analyzed by two
      dimensional (2-D) gel electrophoresis. Twenty-seven proteins with differences in
      expression levels between RCC patients and healthy volunteers were identified. Of
      these, 19 were expressed at different levels and eight were expressed in serum
      from the RCC group, but not from the control group. Six differentially expressed
      proteins identified by using mass spectrometry included coagulation factor XIII
      B, complement C3 and its precursor, misato homolog 1 (isoform CRA_b), hemopexin,
      and alpha-1-B-glycoprotein. Some of these serum proteins are known regulators of
      tumor progression in human malignancies. In conclusion, we successfully applied 2
      D gel electrophoresis and identified six serum proteins differentially expressed
      between patients with small RCC and healthy volunteers. These proteins may
      provide novel biomarkers for early detection and diagnosis of human RCC.

PMID- 21174949
TI  - Efficacy of Setarud (IMod), a novel drug with potent anti-toxic stress potential
      in rat inflammatory bowel disease and comparison with dexamethasone and
      infliximab.
AB  - The inflammatory bowel disease (IBD) is an idiopathic, immune-mediated and
      chronic intestinal condition. In the present study, the effect of Setarud (IMOD),
      a novel natural drug with known immunomodulatory, anti-inflammatory and
      antioxidant properties was investigated in experimental colitis in rats and
      compared with the dexamethasone and infliximab. Immunologic colitis was induced
      by intracolonic administration of a mixture of trinitrobenzene sulfonic acid
      (TNBS) and absolute ethanol in male Wistar rats. Animals were divided into 6
      groups of sham (normal group), control (vehicle-treated), positive control
      (dexamethasone 1 mg/kg/day given orally and infliximab 5 mg/kg/day given
      subcutaneously) and 3 Setarud-treated groups (13.3, 20, 30 mg/kg/day given
      intraperitoneally). The treatment continued for 14 consecutive days and then
      animals were decapitated on the day 15 and distal colons were removed for
      macroscopic, microscopic, and biochemical assays. Biochemical markers, including
      TNF-alpha, IL-1beta, ferric reducing/antioxidant power (FRAP), myeloperoxidase
      (MPO) activity and thiobarbitoric acid-reactive substance (TBARS) were measured
      in the homogenate of colonic tissue. A remarkable reduction in macroscopic and
      histological damage scores was observed in the animals treated with Setarud.
      These findings were confirmed by decreased levels of TNF-alpha, interleukin
      1beta, MPO activity and TBARS, and raised levels of FRAP in the colon tissue.
      These observations confirmed the immunomodulatory, anti-inflammatory and
      antioxidant properties of Setarud in experimental colitis, which was comparable
      to those of dexamethasone and infliximab.

PMID- 21174951
TI  - Homology modeling and QSAR analysis of 1,3,4-thiadiazole and 1,3,4-triazole
      derivatives as carbonic anhydrase inhibitors.
AB  - Carbonic anhydrase (CA) inhibitors are very interesting target for designing
      anticancer (hypoxic) and antiglaucoma drugs. In the present study, a 3D homology
      modeling of human carbonic anhydrase-IX (hCA-IX) isozyme, based upon the crystal
      structure of murine CA-XIVA (PDB CODE 1RJ5) was performed, as no experimental 3D
      structures are available. A homology model of hCA-IX was developed and validated.
      To explore the responsible physicochemical properties of 1,3,4-thiadiazole and
      1,3,4-triazole derivatives for carbonic anhydrase inhibition, a quantitative
      structure activity relationship (QSAR) study was performed having hCA-II and hCA
      IX inhibitory activity respectively. In hCA-II and hCA-IX inhibitory activities,
      four significant models with good correlations (> or = 0.945 & > or = 0.926) were
      obtained; two models (models 1 and 3) were selected based on statistical
      criterion. The QSAR study revealed that in case of hCA-II, overall increase in
      size and volume of molecule, introduction of electropositive surfaces might
      increase the inhibitory activity, whereas in case of hCA-IX, decreasing the
      hydrophobicity and introduction of electron releasing substituents might increase
      the hCA-IX inhibitory activity.

PMID- 21174950
TI  - Anti-hyperglycemic and anti-oxidative effect of aqueous extract of Momordica
      charantia pulp and Trigonella foenum graecum seed in alloxan-induced diabetic
      rats.
AB  - Diabetes is an oxidative stress disorder and oxidative damage to tissues such as
      heart, kidney, liver and other organs may be a contributory factor to several
      diabetic complications. Momordica charantia (family: Cucurbitaceae) and
      Trigonella foenum graecum (family: Fabaceae) are used traditionally in Indian
      folk medicine to manage diabetes mellitus. In the present study, the anti
      hyperglycemic and anti-oxidative potential of aqueous extracts of M. charantia
      pulp and seed powder of T. foenum graecum were assessed in alloxan (150 mg/kg
      body weight) induced diabetic rats. Alloxan treatment to the rats could induce
      diabetes as the fasting blood glucose (FBG) levels were > 280 mg/dl. Treatment of
      diabetic rats for 30 days with M. charantia and T. foenum graecum could
      significantly (p < 0.001) improve the FBG levels to near normal glucose levels.
      Antioxidant activities (superoxide dismutase, catalase, reduced glutathione
      content and glutathione-s-transferase) and lipid peroxidation levels were
      measured in heart, kidney and liver tissues of normal, diabetic and experimental
      animals (diabetics + treatment). TBARS levels were significantly (p < 0.001)
      higher and anti-oxidative activities were found low in diabetic group, as
      compared to the control group. Significant (p < 0.001) improvement in both the
      TBARS levels and antioxidant activities were observed when M. charantia and T.
      foenum graecum were given to diabetic rats. Our results clearly demonstrate that
      M. charantia and T. foenum graecum are not only useful in controlling the blood
      glucose levels, but also have antioxidant potential to protect vital organs such
      as heart and kidney against damage caused due to diabetes induced oxidative
      stress.

PMID- 21174952
TI  - Polygalacturonase inhibitor protein from fruits of anthracnose resistant and
      susceptible varieties of Chilli (Capsicum annuum L).
AB  - Chilli fruit is highly susceptible to anthracnose infection at the stage of
      harvest maturity, due to which the fruit yield in the leading commercial variety
      Byadgi is severely affected. Field studies on screening of several varieties for
      resistance to anthracnose have shown that a variety of chilli AR-4/99K is
      resistant to anthracnose infection. In many crops, resistance to fungal attack
      has been correlated with PGIP activity in developing fruits based on which
      transgenic varieties have been developed with resistance to fungi. The present
      study was carried out to determine whether anthracnose resistance in AR-4/99K was
      due to the increased levels of PGIP alone and/ or due to differences, if any, in
      the properties of PGIP. Hence, a comparative study of the properties of
      polygalacturonase inhibitor protein (PGIP) isolated from fruits of anthracnose
      resistant chilli var AR-4/99K and a susceptible variety Byadgi was conducted with
      the objective of utilizing the information in genetic transformation studies.
      Both the PGIPs from anthracnose resistant and susceptible varieties of chilli
      exhibited similarities in the elution pattern on Sephadex gel, DEAE cellulose,
      PAGE and SDS-PAGE. The two PGIPs were active over a wide range of pH and
      temperature. Both PGIPs showed differential inhibitory activity against
      polygalacturonase (PG) secreted by Colletotrichum gleosporoides, C. capsici, C.
      lindemuthianum, Fusarium moniliforme and Sclerotium rolfsii. The inhibitory
      activity of PGIP from both resistant and susceptible varieties was the highest
      (82% and 76%, respectively) against the PG from Colletotrichum capsici, a
      pathogen causing anthracnose rot of chilli, while the activity was lower (1.27 to
      12.3%) on the other fungal PGs. Although PGIP activity decreased with fruit
      maturation in both the varieties, the resistant variety maintained a higher
      activity at 45 days after flowering (DAF) as compared to the susceptible variety
      which helped it to overcome the infection by anthracnose as against the
      susceptible variety (Byadgi) in which PGIP activity was drastically reduced at
      maturity. The molecular mass of PGIP as determined by SDS-PAGE was found to be 37
      kDa. N-terminal sequence analysis of the PGIP showed the first six amino acid
      residues from N-terminal end were Asp-Thr-His-Lys-Ser-Glu (DTHKSE), respectively.
      The similarities in properties of the two PGIPs support the earlier findings that
      resistance of AR-4/99K to anthracnose fungus is a result of its higher PGIP
      activity at maturity.

PMID- 21174953
TI  - Role of H2O2 and cell wall monoamine oxidases in germination of Vigna radiata
      seeds.
AB  - Plant cell wall expresses monoamine oxidases (MAOs) that catalyze oxidation of
      secreted amines and produce H2O2 in the process. The H2O2, so produced is used by
      cell wall peroxidases for lignification of cell wall or for plant defense. The
      natural substrates for these MAOs are elusive, but polyamines and certain
      catecholamines have been proposed as candidates. Reactive oxygen species are also
      known to act as signaling molecules controlling plant metabolism. Mungbean (Vigna
      radiata) has long served as the plant model of choice while studying molecular
      programs followed during germination and seed development. In this study, we
      tested the effect of externally added MAO substrates epinephrine and H2O2 on
      storage protein mobilization in germinating seeds of Vigna radiata. The seeds
      were imbibed in the presence of 50 microM epinephrine and 10 microM H2O2. These
      low concentrations of the two compounds were used to exclude direct effects on
      proteolysis and were arrived at after testing a range of the two and choosing the
      most effective concentration. These seeds showed 11% and 7% decrease in fresh
      weight respectively, indicating greater storage mobilization and a corresponding
      19% and 46% increase in axis length as compared to untreated seeds. Soluble
      protein in seeds treated with epinephrine and H2O2 decreased significantly by 34%
      and 33% as compared to untreated seeds. Electrophoretic analysis of seed proteins
      revealed a startling and selective depletion of storage proteins in treated
      seeds. The results indicated a clear involvement of H2O2 in storage protein
      mobilization in the cotyledons. We propose that H2O2 generated within cell walls
      of seeds serves as a signaling molecule guiding germination events, including
      protein reserve mobilization.

PMID- 21174954
TI  - Dietary restriction prevents diabetogenic effect of streptozotocin in mice.
AB  - The beneficial role of dietary restriction (DR) was studied in streptozotocin
      (STZ)-induced diabetes in mice. The DR mice exhibited the lower blood glucose
      (mg/dl) level as compared to ad libitum (AL) fed ones. After 3 months' DR, STZ
      treatment to both AL and DR mice showed significant (p < 0.001) elevation of the
      blood glucose level in AL-fed mice, while a lower level of glucose was maintained
      in DR-fed mice. The ability of maintaining a low blood glucose level in STZ
      treated DR mice indicated that STZ might have been ineffective from its action on
      beta cells of pancreas by long-term DR. Thus, these findings suggested that DR
      may be an important tool for preventing the diabetic conditions. However, further
      studies are required to know the mechanism(s) of DR protection against
      diabetogenic action of STZ in experimental animals.

PMID- 21174955
TI  - Potential risk of zoonotic infections in recreational areas visited by Sus scrofa
      and Vulpes vulpes. Case study--Wolin Island, Poland.
AB  - The relation between intestinal parasite prevalence in wild boars and red foxes
      and the sanitary condition of the soil in recreational estates were determined.
      The analysis was made based on 36 samples of boar faeces and 22 samples of fox
      faeces, collected in their habitat as well as 60 samples of soil from two
      recreational areas. Two methods were used for faecal samples--flotation and
      direct faecal smear; and flotation in NaNO3 for soil samples examination.
      Zoonotic nematode eggs were recovered from 25.5% of boar faecal samples; they
      were Ascaris suum (22.2%) and Trichuris suis (5.6%). Other parasites found were:
      Metastrongylus sp. (69.4%), Oesophagostomum sp., Strongyloides sp. (36.6%) and
      Physocephalus sp. (8.6%) as well as coccidia (69.4%). In fox faeces, zoonotic
      nematode eggs were recovered from 31.8% of samples, and they were Toxocara canis
      (27.2%) and Ancylostoma caninum (18.2%). Tapeworm eggs were found in 36.4% of
      samples including Taenia sp. (22.7%). The presence of Uncinaria stenocephala
      (45.5%), Capillaria sp. (36.4%), Trichuris vulpis (4.5%) and coccidia (40.1%) was
      also detected. It was shown that both, flotation and faecal smear, as mutually
      complementary should be used for higher rate of detection of parasites in faeces.
      No eggs of zoonotic helminths in soil from recreational areas were found despite
      these areas were accessible to wild animals and pets. This could be explained by
      characteristics of the soil (loose sand soil) as well as by behaviour of the
      parasite hosts in the examined areas.

PMID- 21174956
TI  - Gastrointestinal helminths of dogs in Western Pomerania, Poland.
AB  - A total of 763 fecal samples were collected from dogs in Western Pomerania during
      2006-2007 to determine the gastrointestinal parasite fauna of dogs in this
      region. In the city of Szczecin, 648 fecal samples were collected every month in
      the annual cycle from nine city areas and analysed. Six fecal samples were taken
      at each collection time from each site. A total of 115 fecal samples from rural
      areas were investigated. Each fecal sample was dissected with a needle, checked
      for tapeworm segments and adult forms of nematodes, and examined for parasite
      eggs using Willis-Schlaff flotation method. The mean prevalence of
      gastrointestinal parasite infection among dogs in Western Pomerania was 34.84%.
      The greatest number of samples containing parasites came from the Chociwel
      commune (46.67%), and the smallest number from the city of Szczecin (23.92%). The
      greatest number of samples containing parasites from the city of Szczecin
      originated from the Sloneczne estate (34.72%), and the smallest number from the
      Kasprowicz Park (13.89%). Dogs' feces were found to contain segments of
      Dipylidium caninum (4.07%) and Taenia sp. (3.45%) tapeworms and eggs of five
      species of gastrointestinal nematodes: Uncinaria stenocephala (11%), Toxocara
      canis (20.62%), Toxascaris leonina (2.91%), Ancylostoma sp. (4.61%), and
      Trichuris vulpis (0.27%). The highest prevalence of endoparasite infection among
      dogs was found in July (42.60%) and the lowest in February (5.56%). Both single-
      and multi-species infections were observed. In the area of Szczecin, single
      species infections were the most common (18.83%).

PMID- 21174957
TI  - Toxoplasma gondii antibodies in domestic cats in Olsztyn urban area, Poland.
AB  - The aim of the investigation was to determine the prevalence of T. gondii among a
      domestic cat population in an urban area in Olsztyn. In total, 135 serum samples
      of cats collected in several veterinary outpatient clinics in Olsztyn were
      examined by direct agglutination assay. The Toxo-Screen DA BioMerieux commercial
      test detected anti-Toxoplasma gondii IgG antibodies. The results of studies
      indicated that cats bred under different conditions in the city of Olsztyn have
      contact with various forms of invasive T. gondii. The high percentage of
      seropositive results at a 1:40 dilution (65.9%) suggests a past infection, and
      the high percentage of seropositive cases at a 1:4000 dilution (68,1%) indicates
      a current or recent toxoplasmosis process. This could indicate that there is a
      permanent source of T. gondii infection in the habitable environment of the cats.
      The high percentage of T. gondii seropositive results among domestic cats in
      Olsztyn proves the presence of circulation of the parasite in the environment.

PMID- 21174958
TI  - Low concentrations of atrazine, glyphosate, 2,4-dichlorophenoxyacetic acid, and
      triadimefon exposures have diverse effects on Xenopus laevis organ morphogenesis.
AB  - Many chemicals are released into the environment, and chemical contamination has
      been suggested as a contributing factor to amphibian declines. To add to a
      growing body of knowledge about the impact of individual chemicals on non-target
      organisms, we examined the specificity of deformities induced by exposure to four
      pesticides (atrazine, 2,4-dichloropheoxyacetic acid (2,4-D), triadimefon, and
      glyphosate) in the model amphibian species, Xenopus laevis. We focused on the
      period of organ morphogenesis, as it is frequently found to be particularly
      sensitive to chemical exposure yet also commonly overlooked. We found similar
      levels of intestine malformations and edemas, as well as disruption of skeletal
      muscle, in atrazine and triadimefon exposed tadpoles. The effects of 2,4-D were
      only apparent at the highest concentrations we examined; glyphosate did not
      induce dramatic malformations at the concentrations tested. While researchers
      have shown that it is important to understand how chemical mixtures affect non
      target organisms, our results suggest that it is first crucial to determine how
      these chemicals act independently in order to be able to identify consequences of
      individual pesticide exposure.

PMID- 21174959
TI  - Production and emission of phosphine gas from wetland ecosystems.
AB  - Phosphine is a part of an atmospheric link of phosphorus cycle on earth, which
      could be an important pathway for phosphorus transport in environment. Wetland
      ecosystems are important locations for global biogeochemical phosphorus cycle. In
      this study, production and emission fluxes of free phosphine from four wetlands
      types in southern China were observed in different seasons. The results showed
      that the concentration of phosphine liberated from wetlands was at pg/m3-ng/m3
      level. The emission concentrations of different wetlands followed the sequence:
      paddy field (51.83 +/- 3.06) ng/m3 > or = marsh (46.54 +/- 20.55) ng/m3 > lake
      (37.05 +/- 22.74) ng/m3 >> coastal wetland (1.71 +/- 0.73) ng/m3, the positive
      phosphine emission flux occurred in rice paddy field (6.67 +/- 5.18) ng/(m2 x hr)
      and marsh (6.23 +/- 26.9) ng/(m2 x hr), while a negative phosphine flux of (
      13.11 +/- 35.04) ng/(m2 x hr) was observed on the water-air interface of Lake
      Taihu, suggesting that paddy field and marsh may be important sources for
      phosphine gas in atmosphere, while lake may be a sink of atmospheric phosphine
      gas during the sampling period. Atmospheric phosphine levels and emission flux
      from Yancheng marsh and rice paddy field varied in different seasons and
      vegetational zones. Both diffusion resistance in aqueous phase and temperature
      were dominating factors for the production and transportation of phosphine to
      atmosphere.

PMID- 21174960
TI  - Effect of seed sludge on characteristics and microbial community of aerobic
      granular sludge.
AB  - Aerobic granular sludge was cultivated by using different kinds of seed sludge in
      sequencing batch airlift reactor. The influence of seed sludge on physical and
      chemical properties of granular sludge was studied; the microbial community
      structure was probed by using scanning electron microscope and polymerase chain
      reaction-denaturing gradient gel electrophoresis (PCR-DGGE). The results showed
      that seed sludge played an important role on the formation of aerobic granules.
      Seed sludge taken from beer wastewater treatment plant (inoculum A) was more
      suitable for cultivating aerobic granules than that of sludge from municipal
      wastewater treatment plant (inoculum B). Cultivated with inoculum A, large amount
      of mature granules formed after 35 days operation, its SVI reached 32.75 mL/g,
      and SOUR of granular sludge was beyond 1.10 mg/(g x min). By contrast, it needed
      56 days obtaining mature granules using inoculum B. DGGE profiles indicated that
      the dominant microbial species in mature granules were 18 and 11 OTU when
      inoculum A and B were respectively employed as seed sludge. The sequencing
      results suggested that dominant species in mature granules cultivated by inoculum
      A were Paracoccus sp., Devosia hwasunensi, Pseudoxanthomonas sp., while the
      dominant species were Lactococcus raffinolactis and Pseudomonas sp. in granules
      developed from inoculum B.

PMID- 21174961
TI  - Hydraulic characteristics of an anaerobic baffled reactor as onsite wastewater
      treatment system.
AB  - The feasibility of using anaerobic baffled reactor (ABR) as onsite wastewater
      treatment system was discussed. The ABR consisted of one sedimentation chamber
      and three up-flow chambers in series was experimented under different peak flow
      factors (PFF of 1 to 6), superficial gas velocities (between 0.6 and 3.1 cm/hr)
      and hydraulic retention times (HRT) (24, 36 and 48 hr). Residence time
      distribution (RTD) analyses were carried out to investigate the hydraulic
      characteristics of the ABR. It was found that the PFF resulted in hydraulic dead
      space. The dead space did not exceed 13% at PFF of 1, 2 and 4 while there was 2
      fold increase (26%) at PFF of 6. Superficial gas velocities did not result in
      more (biological) dead space. The mixing pattern of ABR tended to be a completely
      mixed reactor when PFF increased. Superficial gas velocities did not affect
      mixing pattern. The effects of PFF on mixing pattern could be minimized by higher
      HRT (48 hr). The tank-in-series (TIS) model (N = 4) was suitable to describe the
      hydraulic behaviour of the studied system. The HRT of 48 hr was able to maintain
      the mixing pattern under different flow patterns, introducing satisfactory
      hydraulic efficiency. Chemical oxygen demand (COD) and total suspended solids
      (TSS) removals under all flow patterns were achieved more than 85% and 90%,
      respectively. The standard deviation of effluent COD and TSS concentration did
      not exceed 15 mg/L.

PMID- 21174962
TI  - Removal of humic acid from aqueous solution by cetylpyridinium bromide modified
      zeolite.
AB  - Natural zeolite was modified by loading cetylpyridinium bromide (CPB) to create
      more efficient sites for humic acid (HA) adsorption. The natural and CPB modified
      zeolites were characterized with X-ray diffraction, field emission scanning
      electron microscopy, Fourier transform infrared spectroscopy and elemental
      analysis. The effects of various experimental parameters such as contact time,
      initial HA concentration, solution pH and coexistent Ca2+, upon HA adsorption
      onto CPB modified zeolites were evaluated. The results showed that natural
      zeolite had negligible affinity for HA in aqueous solutions, but CPB modified
      zeolites exhibited high adsorption efficiency for HA. A higher CPB loading on
      natural zeolites exhibited a larger HA adsorption capacity. Acidic pH and
      coexistent Ca2+ were proved to be favorable for HA adsorption onto CPB modified
      zeolite. The kinetic process was well described by pseudo second-order model. The
      experimental isotherm data fitted well to Langmuir and Sips models. The maximum
      monolayer adsorption capacity of CPB modified zeolite with surfactant bilayer
      coverage was found to be 92.0 mg/g.

PMID- 21174963
TI  - Fabrication of asymmetric poly (m-phenylene isophthalamide) nanofiltration
      membrane for chromium (VI) removal.
AB  - The feasibility of employing nanofiltration for the removal of chromium (VI) from
      wastewater was investigated. Poly (m-phenylene isophthalamide) (PMIA) was used to
      fabricate asymmetric nanofiltration membrane through the phase-inversion
      technique. Scanning electron microscopy (SEM) and atomic force microscopy (AFM)
      were used to characterize the obtained membrane, and the both confirmed a much
      smoother surface which could reduce membrane fouling. The PMIA membrane showed
      different rejections to electrolytes in a sequence of Na2SO4 > MgSO4 > NaCl >
      MgCl2, which was similar to the sequence of the negatively charged nanofiltration
      membranes. Separation experiments on chromium(VI) solution were conducted at
      various operating conditions, such as feed concentration, applied pressure and
      pH. It is concluded that chromium(VI) could be effectively removed from chromium
      containing wastewater by the PMIA nanofiltration membranes while maintaining
      their pollution resistance under alkaline condition.

PMID- 21174964
TI  - Experimental study on pressurized activated sludge process for high concentration
      pesticide wastewater.
AB  - Pressurized biochemical process derived from traditional activated sludge
      processes is an innovative technology for wastewater treatment. The main
      advantage of the pressurized process is that the oxygen transfer barrier can be
      overcome by increasing the dissolved oxygen level. In this study, high
      concentration pesticide wastewater was treated by pressurized activated sludge
      process. It was found that the removal of chemical oxygen demand (COD) increased
      steadily with the increase of operating pressure, aeration time, and sludge
      concentration. When the operation pressure was 0.30 MPa and the aeration time was
      6 hr, 85.0%-92.5% COD, corresponding to an effluent COD of 230-370 mg/L, was
      removed from an influent COD of 2500-5000 mg/L. The obtained outlet COD
      concentration was lower than 350-450 mg/L for the identical process operated
      under the atmospheric pressure. In addition, pressurized biochemical process
      could produce a higher COD volumetric loading rate at 5.8-7.6 kg COD/(m3.day),
      compared with 2.0-2.8 kg COD/(m3.day) using the same equipment at the atmospheric
      pressure. The COD concentration followed a modified Monod model with Vmax 2.31
      day-' and K(S) 487 mg/L.

PMID- 21174965
TI  - Ambient levels of atmospheric carbonyls in Beijing during the 2008 Olympic Games.
AB  - The measurements of atmospheric carbonyls concentrations in Beijing were
      conducted from 12 July to 8 October, 2008, covering the periods of the 2008
      Olympic Games and Paralympic Games. Six carbonyls, including formaldehyde,
      acetaldehyde, acetone, butyraldehyde, valeraldehyde, and hexaldehyde, were
      identified in all air samples. The total average concentrations of these
      carbonyls before, during, and after traffic restriction were (48.1 +/- 15.2),
      (36.6 +/- 14.5) and (23.4 +/- 12.3) microg/m3, respectively. Compared with the
      period after traffic restriction, the distinct high concentrations of the
      carbonyls before and during traffic restriction were primarily ascribed to the
      remarkable contribution of photochemical reactions. With respect to our previous
      investigation in the summer of 2005, the reductions of formaldehyde, acetaldehyde
      and acetone during traffic restriction period were about 64%, 47% and 27%,
      respectively, indicating that the air cleaning actions adopted by the Chinese
      government for the two games were efficient. The lowest levels of atmospheric
      carbonyls and the extremely high composition proportion of acetone after the
      traffic restriction were mainly attributed to the long-term effect of the control
      measures for the two games.

PMID- 21174966
TI  - Instrumental and bio-monitoring of heavy metal and nanoparticle emissions from
      diesel engine exhaust in controlled environment.
AB  - In the present article we characterized the emissions at the exhaust of a Common
      Rail (CR) diesel engine, representative of light-duty class, equipped with a
      catalyzed diesel particulate filter (CDPF) in controlled environment. The
      downstream exhausts were directly analyzed (for PM, CO, CO2, 02, HCs, NOx) by
      infrared and electrochemical sensors, and SEM-EDS microscope; heavy metals were
      chemically analyzed using mosses and lichens in bags, and glass-fibre filters all
      exposed at the engine exhausts. The highest particle emission value was in the 7
      54 nm size range; the peak concentration rose until one order of magnitude for
      the highest load and speed. Particle composition was mainly carbonaceous,
      associated to noticeable amounts of Fe and silica fibres. Moreover, the content
      of Cu, Fe, Na, Ni and Zn in both moss and lichen, and of Al and Cr in moss, was
      significantly increased. Glass-fibre filters were significantly enriched in Al,
      B, Ba, Cu, Fe, Na, and Zn. The role of diesel engines as source of carbonaceous
      nanoparticles has been confirmed, while further investigations in controlled
      environment are needed to test the catalytic muffler as a possible source of
      silica fibres considered very hazardous for human health.

PMID- 21174967
TI  - A land use regression for predicting NO2 and PM10 concentrations in different
      seasons in Tianjin region, China.
AB  - Land use regression (LUR) model was employed to predict the spatial concentration
      distribution of NO2 and PM10 in the Tianjin region based on the environmental air
      quality monitoring data. Four multiple linear regression (MLR) equations were
      established based on the most significant variables for NO2 in heating season (R2
      = 0.74), and non-heating season (R2 = 0.61) in the whole study area; and PM10 in
      heating season (R2 = 0.72), and non-heating season (R2 = 0.49). Maps of spatial
      concentration distribution for NO2 and PM10 were obtained based on the MLR
      equations (resolution is 10 km). Intercepts of MLR equations were 0.050 (NO2,
      heating season), 0.035 (NO2, non-heating season), 0.068 (PM10, heating season),
      and 0.092 (PM10, non-heating season) in the whole study area. In the central area
      of Tianjin region, the intercepts were 0.042 (NO2, heating season), 0.043 (NO2,
      non-heating season), 0.087 (PM10, heating season), and 0.096 (PM10, non-heating
      season). These intercept values might imply an area's background concentrations.
      Predicted result derived from LUR model in the central area was better than that
      in the whole study area. R2 values increased 0.09 (heating season) and 0.18 (non
      heating season) for NO2, and 0.08 (heating season) and 0.04 (non-heating season)
      for PM10. In terms of R2, LUR model performed more effectively in heating season
      than non-heating season in the study area and gave a better result for NO2
      compared with PM10.

PMID- 21174968
TI  - Degradation of 14C-glyphosate and aminomethylphosphonic acid (AMPA) in three
      agricultural soils.
AB  - Glyphosate (N-phosphonomethyl glycine) is the most used herbicide worldwide. The
      degradation of 14C-labeled glyphosate was studied under controlled laboratory
      conditions in three different agricultural soils: a silt clay loam, a clay loam
      and a sandy loam soil. The kinetic and intensity of glyphosate degradation varied
      considerably over time within the same soil and among different types of soil.
      Our results demonstrated that the mineralization rate of glyphosate was high at
      the beginning of incubation and then decreased with time until the end of the
      experiment. The same kinetic was observed for the water extractable residues. The
      degradation of glyphosate was rapid in the soil with low adsorption capacity
      (clay loam soil) with a short half-life of 4 days. However, the persistence of
      glyphosate in high adsorption capacity, soils increased, with half-live of 19
      days for silt clay loam soil and 14.5 days for sandy loam soil. HPLC analyses
      showed that the main metabolite of glyphosate, aminomethylphosphonic acid (AMPA)
      was detected after three days of incubation in the extracts of all three soils.
      Our results suggested that the possibility of contamination of groundwater by
      glyphosate was high on a long-term period in soils with high adsorption capacity
      and low degrading activities and/or acid similar to sandy loam soil. This risk
      might be faster but less sustainable in soil with low adsorption capacity and
      high degrading activity like the clay loam soil. However, the release of non
      extractable residues may increase the risk of contamination of groundwater
      regardless of the type of soil.

PMID- 21174969
TI  - Effect of electric intensity on the microbial degradation of petroleum pollutants
      in soil.
AB  - Electro-bioremediation is an innovative method to remedy organic-polluted soil.
      However, the principle of electrokinetic technology enhancing the function of
      microbes, especially the relationship of electric intensity and biodegradation
      efficiency, is poorly investigated. Petroleum was employed as a target organic
      pollutant at a level of 50 g/kg (mass of petroleum/mass of dry soil). A direct
      current power supply was used for tests with a constant direct current electric
      voltage (1.0 V/cm). The petroleum concentrations were measured at 3275-3285 nm
      after extraction using hexane, the group composition of crude oil was analyzed by
      column chromatography. The water content of soil was kept 25% (m/m). The results
      indicated the degradation process was divided into two periods: from day 1 to day
      40, from day 41 to day 100. The treatment of soil with an appropriate electric
      field led the bacteria to have a persistent effect in the whole period of 100
      days. The highest biodegradation efficiency of 45.5% was obtained after treatment
      with electric current and bacteria. The electric-bioremediation had a positive
      effect on alkane degradation. The degradation rate of alkane was 1.6 times higher
      in the soil exposed to electric current than that treated with bacteria for 100
      days. A proper direct current could stimulate the microbial activities and
      accelerate the biodegradation of petroleum. There was a positive correlation
      between the electric intensities and the petroleum bioremediation efficiencies
      with a coefficient of 0.9599.

PMID- 21174970
TI  - Releases of phosphate fertilizer industry in the surrounding environment:
      investigation on heavy metals and polonium-210 in soil.
AB  - Distribution of Cu, Zn, Pb, Cr, Ni, Mn concentrations and the activity of
      polonium-210 in the surrounding area of a phosphate fertilizer industry located
      on the eastern coast of the Mediterranean Sea has been determined. Nineteen
      sampling sites were distributed around the industrial zone on a surface area of
      about 100,000 m2. Atomic absorption spectroscopy and Alpha spectroscopy were used
      to quantify the heavy elements and polonium-210, respectively. Investigation on a
      particle scale was conducted by TEM and SEM coupled to EDX and X-ray cartography
      to determine the nature of heavy elements carriers and their distribution. Heavy
      elements were mainly concentrated inside the particle size fraction < 50 microm.
      Their levels decreased with distance increasing from the industry. According to
      the reference soil, enrichment factors were about 10, 15, 32 and 100 times for
      Zn, Pb, Cu, and Cr, respectively inside the particle size fraction < 50 microm on
      the closest sites to the industry. The main contaminant sources were transport
      and storage of row materials and the free release of phosphogypsum waste. Heavy
      elements were entrapped inside agglomerates of sulfates, phosphates and iron
      oxihydroxides in a diffused shape. Polonium-210 with an enrichment factor of
      about 56, showed the same behavior of the spatial distribution of the trace
      elements.

PMID- 21174971
TI  - Chemical composition and Zn bioavailability of the soil solution extracted from
      Zn amended variable charge soils.
AB  - A study on variable charge soils (volcanic Italian and podzolic Scottish soils)
      was performed to investigate the influence of soil properties on the chemical
      composition of soil solution. Zinc speciation, bioavailability and toxicity in
      the soil solution were examined. The soils were spiked with increasing amounts of
      Zn (0, 100, 200, 400 and 1000 mg/kg) and the soil solutions were extracted using
      rhizon soil moisture samplers. The pH, total organic carbon (TOC), base cations,
      anions, total Zn and free Zn2+ in soil solution were analysed. A rapid bioassay
      with the luminescent bacterium Escherichia coli HB101 pUCD607 was performed to
      assess Zn toxicity. The influence of soil type and Zn treatments on the chemical
      composition of soil solution and on Zn toxicity was considered and discussed.
      Different trends of total and free Zn concentrations, base cations desorption and
      luminescence of E. coli HB101 pUCD607 were observed. The soil solution extracted
      from the volcanic soils had very low total and free Zn concentrations and showed
      specific Zn2+/Ca2+ exchange. The soil solution from the podzolic soil had much
      higher total and free Zn concentrations and showed no evidence of specific
      Zn2+/Ca2+ exchange. In comparison with the subalkaline volcanic soils, the acidic
      podzol showed enhanced levels of toxic free Zn2+ and consequently stronger
      effects on E. coli viability.

PMID- 21174972
TI  - Production of a newly isolated Paenibacillus polymyxa biocontrol agent using
      monosodium glutamate wastewater and potato wastewater.
AB  - A phyllosphere bacterial strain EBL-06 was isolated from wheat leaves. The
      morphology, cultural characteristics, phospholipid fatty acids, physiological and
      antagonistic fungus activities of this strain were investigated. A phylogenetic
      tree was constructed by comparing with the published 16S rDNA sequences of the
      relevant bacteria. The results showed that the isolate EBL-06 was a strain of
      Paenibacillus polymyxa; this strain performed a high level of antagonistic fungus
      activity toward a broad spectrum of phytopathogens, such as Botrytis cinerea,
      Cladosporium cucumerinum, Fusarium spp. The isolate EBL-06 can grow well using
      monosodium glutamate wastewater (MGW) and potato wastewater (PW) as culture
      medium. The maximum yield of 6.5 x 10(9) CFU/mL of the isolate EBL-06 anti-fungus
      biocontrol agent was reached in 15 hr cultivation at 28 degrees C, pH 6.0-7.5
      using the mixture of MGW and PW (1:9).

PMID- 21174973
TI  - Assessment of oxidative stress indices in a marine macro brown alga Padina
      tetrastromatica (Hauck) from comparable polluted coastal regions of the Arabian
      Sea, west coast of India.
AB  - Oxidative stress and antioxidant defence systems were assessed in a marine brown
      alga Padina tetrastromatica, commonly occurring from the tropics. Lipid
      peroxidation (LPX) and H2O2 were measured as oxidative stress markers, and
      antioxidant defences were measured as catalase (CAT), glutathione S-transferase
      (GST) and ascorbic acid (AsA), in order to understand their dissimilarity with
      respect to pollution levels from selective locations along the central west coast
      of India. A significant increased levels of LPX, H2O2, CAT and GST were observed
      in samples from relatively polluted localities (Colaba and Karwar) when compared
      to less polluted locality (Anjuna), while AsA concentration was higher in algal
      samples from worst polluted region of Colaba. Heavy metals such as Cd and Pb were
      also higher in the vicinity of polluted areas compared to reference area.
      Variation of oxidative stress indices in response to accumulation of heavy metals
      within P. tetrastromatica could be used as molecular biomarkers in assessment and
      monitoring environmental quality of ecologically sensitive marine habitats.

PMID- 21174974
TI  - Abundance and community of snow bacteria from three glaciers in the Tibetan
      Plateau.
AB  - Bacterial abundance and diversity in snow of East Rongbuk, Laohugou and Hailuogou
      glaciers on the Tibetan Plateau were investigated through epifluorescence
      microscope and denaturing gradient gel electrophoresis. Cell abundance ranged
      from 4.0 x 10(3) to 290.2 x 10(3) cells/mL. The phylogenetic trees placed the 16S
      rRNA sequences in four major groups: Proteobacteria, Firmicutes, Actinobacteria
      and Bacteroidetes. Brevundimonas, Flavobacterium, Hymenobacter, Bacillus,
      Polaromonas, Rhodoferax and Streptomyces were widely distributed bacteria in
      glaciers from different cold regions. The remaining five genera of Hylemonella,
      Delftia, Zoogloea, Blastococcus and Rhodococcus were endemism, only recovered
      from our investigated glaciers. It is proposed that the three glaciers on the
      Tibetan Plateau provide a specific ecological niche for prolonging survival of
      diverse microbial lineages.

PMID- 21174975
TI  - Debrominated and methoxylated polybrominated diphenyl ether metabolites in
      rainbow trout (Oncorhynchus mykiss) after exposure to decabromodiphenyl ether.
AB  - Decabromodiphenyl ether (BDE209) is the primary component in a commonly used
      flame retardant. Previous studies had proved that BDE209 itself was not toxic,
      while its metabolites including debrominated diphenyl ethers (De-BDEs) and
      methoxylated brominated diphenyl ethers (MeO-BDEs) posed a potential threat to
      organisms. Many studies had indicated that BDE209 could metabolize quickly in
      mammals, but lacking in the basic data about the metabolism of BDE209 in fish. In
      the present study, two replicate treatment groups of rainbow trout (Oncorhynchus
      mykiss) were exposed to BDE209 via a single intraperitoneal injection
      approximately 100 and 500 ng/g, respectively. Muscle, liver and blood samples
      were collected to analyze the specific metabolites on day 1 and day 28 post
      injection. The highest concentration of BDE209 was detected in muscle tissues,
      from 796.1 ng/g wet weight (day 1) to 687.1 ng/g wet weight (day 28) in high dose
      group, suggesting that BDE209 could accumulate slightly in muscle tissues.
      However, BDE209 was not detected in the blood for all treatments. Most congeners
      of De-BDEs were found in muscle and liver tissues, with the highest concentration
      in the liver. The main De-BDEs were nona-, octa-, hepta- and penta-De-BDEs. A
      total of seven MeO-BDE metabolites were observed among different fish tissues.
      Blood had the highest contribution of the MeO-BDE metabolites. Each MeO-BDE
      congener increased over the 28 days. These results in contrast to other studies
      suggested possible species-specific differences in metabolic abilities.

PMID- 21174976
TI  - Effects of chronic exposure to nonylphenol on locomotor activity and social
      behavior in zebrafish (Danio rerio).
AB  - Nonylphenol (NP), a xenoestrogen ubiquitously found in aquatic ecosystems, is of
      high environmental concern. The present work assessed the effects of exposure to
      NP on locomotor activity and social behavior in male and female zebrafish (Danio
      rerio), to evaluate the possible hazard of NP to fish behavior and to pursue a
      potential biomarker of NP contamination. Fish were randomly divided into six
      groups. Five groups were receiving 0.1, 1, 10, 50 and 100 microg/L nominal
      concentrations of NP for 60 days, respectively. A sixth control group was given
      the same treatment as the other five groups, but no NP. Locomotor activity,
      aggressive behavior, group preference and leaving shoal were examined. NP
      exposure showed marked influence on locomotor activity of the male zebrafish,
      whereas that of the female was not significantly affected by NP. Aggressive
      behavior and group preference were significantly affected by NP exposure in both
      male and female groups. Locomotor activity and aggressive behavior of the male
      and group preference of both male and female zebrafish were clearly inhibited at
      100 microg/L NP. No significant alteration in leaving shoal was observed under NP
      exposure. The results suggested that changes in locomotor activity and aggressive
      behavior of the male and group preference of both male and female may be used as
      an ecologically relevant integrative biomarker of NP contamination.

PMID- 21174977
TI  - Performance and mechanism study for low-temperature SCR of NO with propylene in
      excess oxygen over Pt/TiO2 catalyst.
AB  - A 0.5 wt.% Pt/TiO2 catalyst was prepared and used for the low-temperature
      selective catalytic reduction (SCR) of NO with C3H6 in the presence of excess
      oxygen. The effects of Pt loading and O2 concentration on Pt/TiO2 catalytic
      performance for low-temperature SCR were investigated. It was found that optimal
      Pt loading was 0.5 wt.% and excess O2 favored low-temperature SCR of NOx. The
      mechanism of low-temperature SCR of NO with C3H6 was investigated with respect to
      the behavior of adsorbed species over Pt/TiO2 at 150 degrees C using in situ
      DRIFTS. The results indicated that surface nitrosyl species (Ptdelta(+)-NO and
      Ti3(+)-NO) and Pt2(+)-CO are main reaction intermediates during the interactions
      of NO, C3H6 and O2. A simplified NO decomposition mechanism for the low
      temperature SCR of NO with C3H6 was proposed.

PMID- 21174978
TI  - Iron-doped Mn-Ce/TiO2 catalyst for low temperature selective catalytic reduction
      of NO with NH3.
AB  - The catalysts of iron-doped Mn-Ce/TiO2 (Fe-Mn-Ce/TiO2) prepared by sol-gel method
      were investigated for low temperature selective catalytic reduction (SCR) of NO
      with NH3. It was found that the NO conversion over Fe-Mn-Ce/TiO2 was obviously
      improved after iron doping compared with that over Mn-Ce/TiO2. Fe-Mn-Ce/TiO2 with
      the molar ratio of Fe/Ti = 0.1 exhibited the highest activity. The results showed
      that 96.8% NO conversion was obtained over Fe (0.1)-Mn-Ce/TiO2 at 180 degrees C
      at a space velocity of 50,000 hr(-1). Fe-Mn-Ce/TiO2 exhibited much higher
      resistance to H2O and SO2 than that of Mn-Ce/TiO2. The properties of the
      catalysts were characterized using X-ray diffraction (XRD), N2 adsorption,
      temperature programmed desorption (NH3-TPD and NOx-TPD), and Xray photoelectron
      spectroscopy (XPS) techniques. BET, NH3-TPD and NOx-TPD results showed that the
      specific surface area and NH3 and NOx adsorption capacity of the catalysts
      increased with iron doping. It was known from XPS analysis that iron valence
      state on the surface of the catalysts were in Fe3+ state. The doping of iron
      enhanced the dispersion and oxidation state of Mn and Ce on the surface of the
      catalysts. The oxygen concentrations on the surface of the catalysts were found
      to increase after iron doping. Fe-Mn-Ce/TiO2 represented a promising catalyst for
      low temperature SCR of NO with NH3 in the presence of H2O and SO2.

PMID- 21174979
TI  - Degradation of Reactive Yellow 86 with photo-Fenton process driven by solar
      light.
AB  - The decolorization of Reactive Yellow 86 (RY 86), one of reactive azo dyes, was
      investigated in the presence of Fenton reagent under solar light irradiation. The
      decolorization rate was strongly influenced by pH, initial concentrations of H2O2
      and Fe(II), and so on. An initial concentration of 40 mg/L was decolored more
      than 90% after 20 min under optimum conditions. The activation energy of the
      solar photo-Fenton reaction was 1.50 kJ/mol for RY 86 in the temperature range of
      10-60 degrees C. In the kinetic study, the rate constant of RY 86 with OH.
      radicals could be estimated to be 1.7 x 10(10) L/(mol.sec). The decolorization
      efficiency of RY 86 under solar light irradiation was comparable to the
      artificial light irradiation. The decrease of TOC as a result of mineralization
      of RY 86 was observed during photo-Fenton process. The rate of RY 86
      mineralization was about 83% under UV irradiation after 24 hr. The formation of
      chloride, sulfate, nitrate and ammonium ions as end-products was observed during
      the photocatalytic process. The decomposition of RY 86 gave two kinds of
      intermediate products. The degradation mechanism of RY 86 was proposed on the
      base of the identified intermediates.

PMID- 21174980
TI  - Sustainable oil-in-water analysis using a supercritical fluid carbon dioxide
      extraction system directly interfaced with infrared spectroscopy.
AB  - A direct aqueous supercritical fluid extraction (SFE) system using carbon dioxide
      provides a sustainable means by which a vast range of industries may continue to
      depend on well established infrared (IR) techniques to determine oil-in-water.
      The SFE-IR method provides an environmentally friendly substitute for current
      national standard IR reference methods for measuring oil-in-water that rely on
      using increasingly restricted ozone depleting solvents whose manufacture is being
      phased out in accordance with international law. The SFE-IR analysis of a 500 mL
      water sample can be accomplished in 15 min. A rapid on-line SFE-IR calibration
      method has been implemented. With this calibration method, SFE-IR accuracy for
      determining diesel oil in 500 mL spiked water samples using single wave number
      measurement was 86.0%-98.8% with precision (RSD) ranging from 2.5%-7.0%. Using a
      general purpose calculation which involves measuring infrared absorbance values
      at three different wave numbers, SFE-IR method accuracy for determining diesel
      oil in 500 mL spiked water samples was 83.7%-92.2% with RSD 1.0%-9.3%. Data is
      presented that indicates current long established national standard IR reference
      methods involving three wave number calculations should be reviewed since,
      without careful consideration, the inclusion of calculated aromatic hydrocarbon
      species contributions to final oil-in-water concentration values may provide less
      accurate results.

PMID- 21174981
TI  - Construction of WCB-11: a novel phiYFP arsenic-resistant whole-cell biosensor.
AB  - The prediction and assessment of environmental pollution by arsenic are important
      preconditions of advocating environmental protection and human health risk
      assessment. A yellow fluorescent protein-based whole-cell biosensor for the
      detection of arsenite and arsenate was constructed and tested. An arsenic
      resistant promoter and the regulatory gene arsR were obtained by PCR from the
      genome of Escherichia coli DH5alpha, and phiYFP was introduced into E. coli
      DH5alpha as a reporter gene to construct an arsenic-resistant whole-cell
      biosensor (WCB-11) in which phiYFP was expressed well for the first time.
      Experimental results demonstrated that the biosensor has a good response to
      arsenic and the expression of phiYFP. When strain WCB-11 was exposed to As3+ and
      As5+, the expression of yellow fluorescence was time-dependent and dose
      dependent. This engineered construct is expected to become established as an
      inexpensive and convenient method for the detection of arsenic in the field.

PMID- 21174982
TI  - Application of stimulating agents on the immobilized bioluminescence strain
      Pseudomonas putida mt-2 KG1206, preserved by deep-freezing, for the convenient
      biomonitoring.
AB  - This study was conducted to develop methods for the application of an immobilized
      bioluminescence strain (KG1206), preserved by deep-freezing (DF), for the
      monitoring of contaminated environments. The immobilized cells, preserved by DF,
      required approximately 2 hr for reconstitution of their activity. A large
      reduction in bioluminescence was observed due to the DF process; 0.07-0.58 times
      that of the non deep-frozen (NDF) immobilized strain. The decreased
      bioluminescence activity induced by the DF process was enhanced by the
      stimulants, sodium lactate (SL) and KNO3. However, regardless of the inducer
      chemical tested, the immobilized strain modified with KNO3 consistently produced
      greater bioluminescence than that treated with SL, in the range of 3.0-10.7 (avg.
      6.7 +/- 3.69) and 1.2-4.2 (avg. 2.4 +/- 1.47) times that of control,
      respectively. All KNO3 treatments of contaminated groundwater samples also
      resulted in an increase in bioluminescence activity, but the rate of stimulation
      varied for each sample. Also, no strong linear correlation was observed between
      the bioluminescence and the total concentration of an inducer, which may related
      to the complex characteristics of the environmental samples. Overall, the results
      demonstrated the ability of immobilized genetically engineered bacteria,
      preserved by DF, to measure a specific group of environmental contaminants using
      a stimulating agent (KNO3), suggesting the potential for its preliminary
      application in a field-ready bioassay.

PMID- 21174983
TI  - Contributions of biofilm and suspended sludge to nitrogen transformation and
      nitrous oxide emission in hybrid sequencing batch system.
AB  - Hybrid system combines the nature of suspended growth and attached growth has
      been widely applied to wastewater treatment. In this research, the contributions
      to N transformation and N2O emission by biofilm and suspended sludge in the
      hybrid sequencing-batch reactor for a simultaneous nitrification, denitrification
      and phosphorus removal process were investigated. For the hybrid system,
      nitrification occurred mostly in the suspended sludge, while the biofilm played
      the major role in denitrification. The interaction of the biofilm and the
      suspended sludge in the same reactor resulted in a better overall nitrogen
      removal performance with simultaneous nitrification and denitrification. However,
      N2O emission was the main end product of nitrogen removal for the hybrid system;
      while it was N2 for the biofilm. The relative low N2O emissions from the pure
      biofilm and the pure suspended sludge corresponded to the relatively high nitrate
      at the end of the aeration period compared with the hybrid system.

PMID- 21174984
TI  - Seasonal variation of potential denitrification rates of surface sediment from
      Meiliang Bay, Taihu Lake, China.
AB  - The regulatory effects of environmental factors on denitrification were studied
      in the sediments of Meiliang Bay, Taihu Lake, in a monthly sampling campaign over
      a one-year period. Denitrification rates were measured in slurries of field
      samples and enrichment experiments using the acetylene inhibition technique.
      Sediment denitrification rates in inner bay and outer bay ranged from 2.8 to 51.5
      nmol N2/(g dw (dry weight) x hr) and from 1.5 to 81.1 nmol N2/(g dw x hr),
      respectively. Sediment denitrification rates were greatest in the spring and
      lowest in the summer and early autumn, due primarily to seasonal differences in
      nitrate concentration and water temperature. For each site, positive and linear
      relationships were regularly observed between denitrification rate and water
      column nitrate concentration. Of various environmental factors on denitrification
      that we assessed, nitrate was determined to be the key factor limiting
      denitrification rates in the sediments of Meiliang Bay. In addition, at the two
      sites denitrification rates were also regulated by temperature. The addition of
      organic substrates had no significant effect on denitrification rate, indicating
      that sediment denitrification was not limited by organic carbon availability in
      the sediments. Nitrate in the water column was depleted during summer and early
      autumn, and this suppressed effective removal of nitrogen from Taihu Lake by
      denitrification.

PMID- 21174985
TI  - Temporal variability of iron concentrations and fractions in wetland waters in
      Sanjiang Plain, northeast China.
AB  - Chemical forms, reactivities and transformation of iron fractions in marshy
      waters were investigated with cross-flow filtration technique to study the iron
      environmental behavior. Iron fractions were divided into four parts: acid-labile
      iron (pre-acidification of unfiltered marshy water samples, > 0.7 microm), high
      molecular-weight iron (0.7-0.05 microm), medium-molecular-weight iron (0.05-0.01
      microm), and low-molecular-weight iron (< 0.01 microm). The cross-flow filtration
      suggested that iron primarily exist in both the > 0.7 microm and < 0.01 microm
      size fractions in marshy waters. Rainfall is the key for rain-fed wetland to
      determine fate of iron by changing the aquatic biochemical conditions. By
      monitoring the variation of iron concentrations and fractions over three years,
      it was found that dissolved iron and acid-labile iron concentrations exhibit a
      large variation extent under different annual rainfalls from 2006 to 2008. The
      seasonal variation for iron species proved that the surface temperature could
      control some conversion reactions of iron in marshy waters. Low-molecular-weight
      iron would convert to acid-labile iron gradually with temperature decreasing. The
      photochemical reactions of iron fractions, especially low-molecular-weight iron
      had occurred under solar irradiation. The relative proportion of low-molecular
      weight in total dissolved iron ranging from 28.3% to 43.2% were found during the
      day time, which proved that the observed decreasing concentration of acid
      lability iron was caused by its degradation to low molecular weight iron.

PMID- 21174986
TI  - Short-term metal accumulation and MTLP induction in the digestive glands of Perna
      virdis exposed to Zn and Cd.
AB  - Time-dependent Zn and Cd accumulation and metallothionein like protein (MTLP)
      induction in the digestive glands of mussels, Perna virdis, were measured under
      different exposure conditions. The initial uptake rate at start of chase (rho0)
      and mean residence time (tau) were calculated to determine the physiological
      response of organisms and their potential detoxification mechanisms. It was found
      that in digestive glands, Zn had obviously higher rho0 and shorter mean residence
      time than Cd, indicating that these two metals had different accumulation
      dynamics even though they were very close in the periodic element table. MTLP
      levels in digestive glands varied from 0.51 to 1.05 microg/g ww (wet weight). The
      MTLP level increased continuously when mussels were exposed to low and middle
      levels of Zn and Cd media, and reached maximal levels at day 4, then decreased
      when they were exposed to high level Zn and Cd solutions. With regard to the
      fraction of Zn and Cd accumulated in the digestive glands, the ratios of soluble
      metal to total metal decreased continuously after exposure in low and middle
      levels of Zn and Cd media, and decreased continuously in the first 4 days and
      then to level off when mussels were exposed to media with high concentration of
      Zn and Cd. Results suggested that both MTLP induction and metal insolubilization
      were detoxification processes in digestive glands of mussels.

PMID- 21174987
TI  - Assessing high resolution oxidation-reduction potential and soluble reactive
      phosphorus variation across vertical sediments and water layers in Xinghu Lake: a
      novel laboratory approach.
AB  - To understand the transfer process of soluble reactive phosphorus (SRP) on the
      lake sediment-water interface in a mesotrophic shallow lake in South China, the
      SRP concentrations and the oxidation-reduction potential (ORP) across the
      sediment-water interfaces were continually monitored. Sediment samples were
      collected from Xinghu Lake in Guangdong Province. The ORP dynamics at different
      layers of overlying water was similar for six experimental systems, whereas those
      in porewater were significantly different. The ORP in overlying water was 200-300
      mV higher than those in sediments. The oxygen penetration depth ranged from 2 to
      10 mm in Xiannu Lake sediments. The variation amplitudes of ORP increased with
      sediment depth, but the mean ORP values were all about 218 mV. The SRP
      concentrations in porewater maintained at a low level of about 0.049 mg/L because
      of high atom ratio of total iron and total manganese to total phosphorus. The SRP
      concentrations and variation amplitudes in porewater increased with sediment
      depth. The SRP in overlying water mainly originated from SRP transference of the
      porewater of middle and bottom sediments (3-15 cm). The ORP variation and SRP
      transfer in porewater played important roles in changing SRP concentrations. A
      distinct SRP concentration gradient appeared in overlying water when intense
      exchange occurred at the sediment-water interface; therefore, it was necessary to
      monitor the SRP concentration profiles to accurately estimate the internal
      loading.

PMID- 21174988
TI  - Naval derusting wastewater containing high concentration of iron, treated in UV
      photo-Fenton-like oxidation.
AB  - The UV photooxidation with Fe(III) and H2O2 was employed to treat a naval
      derusting wastewater, which contains the high COD (chemical oxygen demand) and
      various metal concentrations exceptionally with high concentrations of citric
      acid and iron. Because of its iron containment, the Fenton-like reaction
      automatically took place with the added amount of H2O2. The decomposition rate
      was found in a sequence of: UV/H2O2/Fe(III) > UV/H2O2 > Fe(II)/H2O2. Two H2O2
      injection methods, single and multiple points, were evaluated. The multiple-point
      H202 injection was more efficient to decompose the citric acid. The decomposition
      of the synthetic citric acid and the real derusting citric acid wastewater was
      also compared. The 93% COD reduction of the derusting wastewater was achieved
      using the UV/H2O2/Fe(III) treatment.

PMID- 21174989
TI  - Characteristics and source identification of fine particulate n-alkanes in
      Beijing, China.
AB  - Ambient particulate n-alkanes were determined for fine particle (PM2.5) samples
      collected from Sep 2003 to July 2004 in Beijing, China. The average concentration
      of total n-alkanes (sigma n-alkanes) from C11 to C34 was 425.72 ng/m3, ranged
      from 7.02 to 2893.28 ng/m3. The concentration distributions of n-alkanes
      homologues in this study exhibited peaks at C21 and C29 in heating season, and
      C29 in non-heating season. The average carbon preference index (CPI) value was
      1.88 in the range of 1.18-3.88. The maximum CPI in summer indicated the
      contribution of biogenic origins such as plant wax; while the minimum CPI value
      in winter was probably a result of fossil fuel combustion. Preliminary estimation
      from these results showed that 59% of the n-alkanes in PM2.5 in Beijing summer
      originated from plant wax, while 74%-88% was from fossil fuel combustion in other
      three seasons. Source estimation was further performed using principal component
      analysis method. Two major components were yielded accounting for 57.3% and 30.9%
      of the total variance, which presented the fossil fuel and biogenic contribution,
      respectively.

PMID- 21174990
TI  - Concentrations of heavy metals and polycyclic aromatic hydrocarbons in needles of
      Masson pine (Pinus massoniana L.) growing nearby different industrial sources.
AB  - Emissions from industrial activities pose a serious threat to human health and
      impose the need for monitoring both inorganic and organic pollutants in
      industrial areas. We selected Masson pine (Pinus massoniana L.) as potential
      biomonitor and collected the current (C) and previous year (C+1) needles from
      three industrial sites dominated by petrochemical, ceramics manufacturing, and
      iron and steel smelting plants and one remote site to determine heavy metals (Cu,
      Cd, Pb, Zn, Cr, Ni and Co) and polycyclic aromatic hydrocarbons (PAHs) in
      unwashed and water-washed needles. Both unwashed and washed C+1 needles showed
      generally higher concentrations of heavy metals and PAHs than C needles, although
      the washed needles more clearly spotlighted the accumulation effect of PAHs over
      exposure time. Water-washing resulted in a significant decrease in needle PAH
      concentrations with more significant effects shown in C needles. By contrast,
      needle heavy metal concentrations were much less affected by washing. Although
      heavy metals and PAHs might differ in adsorption and uptake strategies, their
      higher concentrations in the needles at the industrial sites indicated
      conspicuous contamination due to industrial emissions there. The PAH distribution
      patterns in pine needles accorded with the real types of energy consumption in
      the study sites and were efficiently used for pinpointing local pollutant
      sources.

PMID- 21174991
TI  - Characterization of polycyclic aromatic hydrocarbons and gas/particle
      partitioning in a coastal city, Xiamen, southeast China.
AB  - An intensive sampling program had been undertaken in autumn (October, 2008) and
      winter (December, 2008 and January, 2009) at urban (Xiamen University and Xianyue
      residential area), suburban (Institute of Urban Environment), industrial area
      (Lulian Hotel) and background (Tingxi Reservoir) in Xiamen, Fujian Province, to
      characterize the atmospheric concentration and gas-particle phase partitioning of
      PAHs. The average concentration of total PAHs in winter was almost 1.7 times
      higher than those in autumn. The log scale plot of Kp versus sub-cooled liquid
      vapor pressure (P(L)0 for all the data of autumn and winter season samples gave
      significantly different slopes. The slope for the winter samples (-0.72) was
      steeper than that for the autumn samples (-0.58). The partitioning results
      indicated that slope values varied depending on characteristics of specific site,
      source region and meteorological conditions which play important roles in the
      partitioning of PAHs. In addition, local emission sources had a stronger effect
      on partitioning results than long-transported polluted plume. The sources of PAHs
      in five sampling sites in Xiamen also have been discussed initially. Diagnostic
      ratios showed that the primary source of PAHs in urban, suburban and industrial
      area was from vehicle exhausts. While emission from petrochemical factory and
      power plant was another main contributor to industrial area.

PMID- 21174992
TI  - Seasonal variability of ambient NH3, NO, NO2 and SO2 over Delhi.
AB  - We present the diurnal and seasonal variability of ambient NH3, NO, NO2 and SO2
      over Delhi, India. Ambient NH3, NO and NO2 were measured continuously during
      winter, summer and autumn seasons using NH3- and NOx-analyzer, which operates by
      chemiluminescence method with a higher estimation efficiency (> 90%) than the
      chemical trap method (reproducibility 4.7%). Prominent diurnal, day-to-day and
      seasonal variations of ambient mixing ratio of NH3, NO, NO2 and SO2 were observed
      during the study period. Seasonal variation with higher mixing ratio in winter
      was observed for all measured trace gases except NO. Day-night variation of all
      measured trace gases observed was higher in winter in comparison with summer.
      Late morning increase in NO2 mixing ratio might be attributed to conversion of NO
      to NO2 with the interaction of O3.

PMID- 21174993
TI  - Greenhouse gases fluxes and soil thermal properties in a pasture in central
      Missouri.
AB  - Fluctuations of greenhouse gases emissions and soil properties occur at short
      spatial and temporal scales, however, results are often reported for larger
      scales studies. We monitored CO2, CH4, and N2O fluxes and soil temperature (T),
      thermal conductivity (K), resistivity (R) and thermal diffusivity (D) from 2004
      to 2006 in a pasture. Soil air samples for determination of CO2, CH4 and N20
      concentrations were collected from static and vented chambers and analyzed within
      two hours of collection with a gas chromatograph. T, K, R and D were measured in
      situ using a KD2 probe. Soil samples were also taken for measurements of soil
      chemical and physical properties. The pasture acted as a sink in 2004, a source
      in 2005 and again a sink of CH4 in 2006. CO2 and CH4 were highest, but N2O as
      well as T, K and D were lowest in 2004. Only K was correlated with CO2 in 2004
      while T correlated with both N2O (r = 0.76, p = 0.0001) and CO2 (r = 0.88, p =
      0.0001) in 2005. In 2006, all gases fluxes were significantly correlated with T,
      K and R when the data for the entire year were considered. However, an in-depth
      examination of the data revealed the existence of month-to-month shifts, lack of
      correlation and differing spatial structures. These results stress the need for
      further studies on the relationship between soil properties and gases fluxes. K
      and R offer a promise as potential controlling factors for greenhouse gases
      fluxes in this pasture.

PMID- 21174994
TI  - Effects of plant species coexistence on soil enzyme activities and soil microbial
      community structure under Cd and Pb combined pollution.
AB  - The relationship between plant species coexistence and soil microbial communities
      under heavy metal pollution has attracted much attention in ecology. However,
      whether plant species coexistence could offset the impacts of heavy metal
      combined pollution on soil microbial community structure and soil enzymes
      activities is not well studied. The modified ecological dose model and PCR-RAPD
      method were used to assess the effects of two plant species coexistence on soil
      microbial community and enzymes activities subjected to Cd and Pb combined
      stress. The results indicated that monoculture and mixed culture would increased
      microbe populations under Cd and Pb combined stress, and the order of sensitivity
      of microbial community responding to heavy metal stress was: actinomycetes >
      bacteria > fungi. The respirations were significantly higher in planted soil than
      that in unplanted soil. The plant species coexistence could enhance soil enzyme
      activities under Cd and Pb combined. Furthermore, planted soil would be helpful
      to enhance soil genetic polymorphisms, but Cd and Pb pollution would cause a
      decrease on soil genetic polymorphisms. Mixed culture would increase the
      ecological dose 50% (EDs50) values, and the ED50 values for soil enzyme
      activities decreased with increasing culture time. The dehydrogenase was most
      sensitive to metal addition and easily loses activity under low dose of heavy
      metal. However, it was difficult to fully inhibit the phoshpatase activity, and
      urease responded similarly with phosphatase.

PMID- 21174995
TI  - Isolation, identification, Pb(II) biosorption isotherms and kinetics of a lead
      adsorbing penicillium sp. MRF-1 from South Korean mine soil.
AB  - A heavy metal contaminated soil sample collected from a mine in Chonnam Province
      of South Korea was found to be a source of heavy metal adsorbing biosorbents.
      Chemical analyses showed high contents of lead (Pb) at 357 mg/kg and cyanide (CN)
      at 14.6 mg/kg in the soil. The experimental results showed that Penicillium sp.
      MRF-1 was the best lead resistant fungus among the four individual metal tolerant
      fungal species isolated from the soil. Molecular characterization of Penicillium
      sp. MRF-1 was determined using ITS regions sequences. Effects of pH, temperature
      and contact time on adsorption of Pb(II) by Penicillium sp. MRF-1 were studied.
      Favorable conditions for maximum biosportion were found at pH 4 with 3 hr contact
      time. Biosorption of Pb(II) gradually increased with increasing temperature.
      Efficient performance of the biosorbent was described using Langmuir and
      Freundlich isotherms. Adsorption kinetics was studied using pseudo first-order
      and pseudo second-order models. Biosorbent Penicillium sp. MRF-1 showed the
      maximum desorption in alkali conditions. Consistent adsorption/desorption
      potential of the biosorbent in repetitive cycles validated the efficacy of it in
      large scale. SEM studies given notes on surface modification of fungal biomass
      under metal stress and FT-IR results showed the presence of amino groups in the
      surface structure of the biosorbent. In conclusion, the new biosorbent
      Penicillium sp. MRF-1 may potentially be used as an inexpensive, easily
      cultivatable material for the removal of lead from aqueous solution.

PMID- 21174996
TI  - Effect of temperature and moisture on soil organic carbon mineralization of
      predominantly permafrost peatland in the Great Hing'an Mountains, northeastern
      China.
AB  - Boreal peatlands represent a large global carbon pool. The relationships between
      carbon mineralization, soil temperature and moisture in the permafrost peatlands
      of the Great Hing'an Mountains, China, were examined. The CO2 emissions were
      measured during laboratory incubations of samples from four sites under different
      temperatures (5, 10, 15, and 20 degrees C) and moisture contents (0%, 30%, 60%,
      100% water holding capacity (WHC) and completely water saturated). Total carbon
      mineralization ranged from 15.51 to 112.92 mg C under the treatments for all
      sites. Carbon mineralization rates decreased with soil depth, increased with
      temperature, and reached the highest at 60% WHC at the same temperature. The
      calculated temperature coefficient (Q10) values ranged from 1.84 to 2.51 with the
      soil depths and moisture. However, the values were not significantly affected by
      soil moisture and depth for all sites due to the different peat properties (P >
      0.05). We found that the carbon mineralization could be successfully predicted as
      a two-compartment function with temperature and moisture (R2 > 0.96) and total
      carbon mineralization was significantly affected by temperature and moisture (P <
      0.05). Thus, temperature and moisture would play important roles in carbon
      mineralization of permafrost peatlands in the Great Hing'an Mountains, indicating
      that the permafrost peatlands would be sensitive to the environment change, and
      the permafrost peatlands would be potentially mineralized under future climate
      change.

PMID- 21174997
TI  - Variations between rice cultivars in iron and manganese plaque on roots and the
      relation with plant cadmium uptake.
AB  - To understand certain mechanisms causing variations between rice cultivars with
      regard to cadmium uptake and tolerance, pot soil experiments were conducted with
      two rice cultivars of different genotypes under different soil Cd levels. The
      relationships between plant Cd uptake and iron/manganese (Fe/Mn) plaque formation
      on roots were investigated. The results showed that rice cultivars differed
      markedly in Cd uptake and tolerance. Under soil Cd treatments, Cd concentrations
      and accumulations in the cultivar Shanyou 63 (the genotype indica) were
      significantly higher than those in the cultivar Wuyunjing 7 (the genotype
      japonica) (P < 0.01, or P < 0.05), and Shanyou 63 was more sensitive to Cd
      toxicity than Wuyunjing 7. The differences between the rice cultivars were the
      largest at relatively low soil Cd level (i.e., 10 mg/kg). Fe concentrations in
      dithionite-citrate-bicarbonate root extracts of Shanyou 63 were generally lower
      than that of Wuyunjing 7, and the difference was the most significant under the
      treatment of 10 mg Cd/kg soil. The results indicated that the formation of iron
      plaque on rice roots could act as a barrier to soil Cd toxicity, and may be a
      "buffer" or a "reservoir" which could reduce Cd uptake into rice roots. And the
      plaque may contribute, to some extent, to the genotypic differences of rice
      cultivars in Cd uptake and tolerance.

PMID- 21174998
TI  - Delonix regia and Casuarina equisetifolia as passive biomonitors and as
      bioaccumulators of atmospheric trace metals.
AB  - The suitability of two common and ubiquitously distributed and exotic ornamental
      plant species in Nigeria-Delonix regia and Casuarina equisetifolia as biomonitors
      and as effective bioaccumulators of atmospheric trace metals (Cd, Pb, Zn and Cu)
      has been evaluated. Bark and leaf samples from these plant species were collected
      in June and July 2006 at five locations in Benin City. Four of the sampling sites
      were in areas of high traffic density and commercial activities, the fifth site
      is a remote site, selected to act as a control and also to provide background
      information for the metals. The plant samples were collected and processed using
      standard procedures and trace metals were determined using atomic absorption
      spectrometer. The bark of the plants was able to bioaccumulate the trace metals,
      especially Pb which originates from anthropogenic contributions in the city. The
      Pb range of 20.00-70.00 microg/g measured for the bark samples of D. regia,
      exceeded the normal plant Pb concentration of 0.2-20.0 microg/g and most Pb data
      available in literature. The bark of the plants was observed to accumulate more
      metals compared to the leave, while D. regia was found to be slightly better than
      C. equisetifolia in trace metal uptake efficiency. Spatial variations in the
      distributions of Pb and Zn were significant (p < 0.05), and the continuous use of
      leaded fuel in Nigeria was identified as the predominant source of Pb in the
      atmosphere.

PMID- 21174999
TI  - Modelling sulphate-enhanced cadmium uptake by Zea mays from nutrient solution
      under conditions of constant free Cd2+ ion activity.
AB  - A controlled hydroponic experiment was undertaken to investigate Cd uptake in
      relation to the activity of Cd species in solution other than the free ion (Cd2+)
      by maintaining a constant Cd2+ activity under variable SO42- and Cl-
      concentrations exposed to maize (Zea mays var. Cameron) plants. The objectives of
      these experiments were: (1) to distinguish and quantify the different uptake
      rates of free and inorganic-complexed Cd from nutrient solution, and (2) to model
      the uptake of Cd by maize with a Biotic Ligand Model (BLM) in a system which
      facilitates the close examination of root characteristics. Results of the current
      experiments suggest that, in addition to the free ion, CdSO4(0) complexes are
      important factors in determining Cd uptake in nutrient solution by maize plants.
      Higher nominal SO4(2-) concentrations in solution generally resulted in a greater
      Cd accumulation by maize plants than predicted by the Cd2+ activity. A better
      integration of the complete dataset for the 3 harvest times (6, 9 and 11 days
      after treatment) was achieved by including consideration of both the duration of
      Cd exposure and especially the root surface area to express Cd uptake. Similarly,
      the fit of the BLM was also improved when taking into account exposure time and
      expressing uptake in terms of root morphological parameters.

PMID- 21175000
TI  - Inflammatory response and insulin signaling alteration induced by PCB77.
AB  - A specific mechanism whereby inflammation may contribute to cardiovascular
      diseases (CVD), insulin resistance (IR) and type II diabetes is the induction of
      endothelial dysfunction placing the vascular endothelium in a key unifying
      position for the shared pathogenesis of these diseases. However, the mechanisms
      by which PCBs induce endothelial cell dysfunction are not clearly understood. In
      the present study, we used human umbilical vascular endothelial cells (HUVEC) as
      model, and inflammatory response and insulin signaling alteration induced by PCBs
      were examined. Results showed that PCB77 induced the expression of
      proinflammatory cytokines including IL-6 and TNFalpha and induced U937 adhesion
      to HUVEC cells consistent with increased NFkappaB transcription activity. On the
      other hand, PCB77 blocked insulin-activated Akt signaling pathway, which was
      restored by pretreatment with TNFalpha neutralization antibody. In conclusion,
      PCB77 showed the potential to induce the expression of proinflammatory cytokines
      including IL-6, which has been shown to be powerful independent risk predictor of
      CVD. And PCB77 was observed to alter insulin-activated Akt signaling by TNFalpha
      secretion for the first time.

PMID- 21175001
TI  - Responses of Synechocystis sp. PCC 6803 (cyanobacterium) photosystem II to pyrene
      stress.
AB  - In order to explore the mechanism of acute toxicity for pyrene to cyanobacterial
      organisms, the responses of Synechocystis sp. PCC 6803 photosystem II (PS II)
      under pyrene stress were studied. The results showed there was no significant
      difference about the oxygen evolution under 0.125 mg/L pyrene stress when
      compared with control, but it was significantly lower than control at 0.625 mg/L
      pyrene. Polyphasic chlorophyll-a fluorescence transients in cells of
      Synechocystis sp. PCC 6803 exhibited a typical increase including O, J, I, and P
      phases. Fluorescence yield at phases J, I and P declined slightly at 0.125 and
      0.625 mg/L pyrene, and significantly lower than control at 3.125 mg/L. According
      to the parameters deviated from JIP-test, no modification was induced by pyrene
      both at the donor side and at the acceptor side of PS II, and the reaction centre
      of PS II is the primary damaging target. Based on the expressing of four key
      genes (psbA, psbB, psbC and psbO) of PS II, only psbA showed significant
      difference at 3.125 mg/L pyrene when compared with control.

PMID- 21175002
TI  - Responses of two cultivars of Trifolium repens L. to ethylene diurea in relation
      to ambient ozone.
AB  - Three ethylene diurea (EDU) concentrations (0, 150 and 300 mg/L) were used to
      evaluate the negative impact of ozone (O3) on two cultivars of Trifolium repens
      L. cv. Vardan and Bundel grown under natural field conditions in a suburban area
      of Varanasi, India. Mean O3 concentrations varied from 30.3 to 46.6 microg/L
      during the experimental period. Higher photosynthetic pigments and ascorbic acid
      concentrations were noticed in both EDU-treated cultivars over non-EDU-treated
      ones, but a reverse trend was found for lipid peroxidation. Growth parameters and
      biomass also showed increments under EDU treatment of both cultivars. The ratio
      of variable fluorescence to maximum fluorescence increased significantly in
      Vardan but not in Bundel upon EDU treatment. Results revealed that EDU
      concentration of 300 mg/L was more effective to combat the oxidative stress as
      well as protecting plants from O3 injury symptoms. The test cultivar Vardan is
      relatively sensitive to O3, thereby can be used as a bioindicator of O3 pollution
      in areas having higher O3 concentrations. Results also indicated that Bundel has
      more efficient antioxidant defense system than Vardan and hence was more tolerant
      to O3 stress.

PMID- 21175003
TI  - A novel four-way combining catalysts for simultaneous removal of exhaust
      pollutants from diesel engine.
AB  - A novel four-way combining catalysts containing double layers was applied to
      simultaneously remove four kinds of exhaust pollutants (NOx, CO, HC and PM)
      emitted from diesel engine. The four-way catalysts were characterized using
      scanning electron microscope (SEM) and Ultraviolet visible diffuse reflectance
      spectroscopy (UV-Vis DRS). Their catalytic performances were evaluated by
      temperature-programmed reaction technology. The double layer catalysts could
      effectively remove the four main pollutants. The highest catalytic activity was
      given by the two-layered catalysts of La0.6K0.4CoO3/Al2O3 and W/HZSM-5. Under the
      simulated exhaust gases conditions, the peak temperature of the soot combustion
      was 421 degrees C, the maximal conversion of NO to N2 was 74%, the temperature of
      the HC total conversion was 357 degrees C, and the maximum conversion ratio of CO
      was 99%.

PMID- 21175004
TI  - Thermal stabilization of chromium slag by sewage sludge: effects of sludge
      quantity and temperature.
AB  - To investigate the feasibility of detoxifying chromium slag by sewage sludge,
      synthetic chromium slag containing 3% of Cr(VI) was mixed with sewage sludge
      followed by thermal treatment in nitrogen gas for stabilizing chromium. The
      effects of slag to sludge ratio (0.5, 1 and 2) and temperature (200, 300, 500,
      700 and 900 degrees C) on treatment efficiency were investigated. During the
      mixing process before thermal treatment, 59.8%-99.7% of Cr(VI) was reduced, but
      Cr could be easily leached from the reduction product. Increasing heating
      temperature and decreasing slag to sludge ratio strengthened the reduction and
      stabilization of Cr(VI). When the slag to sludge ratio was 0.5 and thermal
      treatment temperature was 300 degrees C, the total leached Cr and Cr(VI) declined
      to 0.55 mg/L and 0.17 mg/L respectively, and 45.5% of Cr in the thermally treated
      residue existed as residual fraction. A two-stage mechanism was proposed for the
      reduction and stabilization of Cr.

PMID- 21175005
TI  - Leachate treatment using a demonstration aged refuse biofilter.
AB  - Approximately 7000 m3 of aged refuse (AR) with a placement of over eight years
      was excavated from Shanghai Refuse Landfill, the largest landfill in China, and
      used for the construction of a two-stage bioreactor (AR biofilter) media for the
      biological treatment of 100 m3 of refuse landfill leachate. It was found that
      over 64% of COD, 96.9%-99.8% of NH4+ -N, and 95.8%-99.8% of BOD5 could be removed
      by the AR biofilter, when the leachate with initial COD, BOD5, and NH4+ -N
      concentrations were 986-4128 mg/L, 264-959 mg/L, and 538-1583 mg/L, respectively.
      The corresponding concentrations in the effluent were reduced to below 300-400
      mg/L, 2-12 mg/L, and 10-20 mg/L, respectively. The effluent was clear and pale
      yellow with suspended solid below 150 mg/L and color below 150 Pt/Co degree.
      Meanwhile, the total nitrogen removal was only 49%-63%, indicating a relative
      poor denitrification capacity of AR biofilter. The effluent pH was neutral and
      the population of Escherichia coli was less than 10(-1) CFU/mL. Hence, it was
      considered that the demonstration project can work well for the effective
      treatment of leachate.

PMID- 21175006
TI  - Photodegradation mechanism of deltamethrin and fenvalerate.
AB  - To understand the degradation and environmental fate of pyrethroids, the process
      of their photodegradation under simulated natural conditions was investigated.
      The results showed that the degradation process follows first-order kinetics. The
      degradation intermediates were identified with gas chromatography-mass
      spectrometry. A plausible mechanism was discussed to explain the process. Several
      influences on degradation process were investigated and reported such as the
      effects of initial concentration of pyrethroids, total time of light irradiation,
      solvents, and light source, as well as the effect of a few substances that exist
      in the environment. This study could be a good reference for the degradation of
      pyrethroids in practical circumstances.

PMID- 21175007
TI  - Overview: integrating computational, cognitive and clinical expertise to
      understand brain network recovery.

PMID- 21175008
TI  - Towards the virtual brain: network modeling of the intact and the damaged brain.
AB  - Neurocomputational models of large-scale brain dynamics utilizing realistic
      connectivity matrices have advanced our understanding of the operational network
      principles in the brain. In particular, spontaneous or resting state activity has
      been studied on various scales of spatial and temporal organization including
      those that relate to physiological, encephalographic and hemodynamic data. In
      this article we focus on the brain from the perspective of a dynamic network and
      discuss the role of its network constituents in shaping brain dynamics. These
      constituents include the brain's structural connectivity, the population dynamics
      of its network nodes and the time delays involved in signal transmission. In
      addition, no discussion of brain dynamics would be complete without considering
      noise and stochastic effects. In fact, there is mounting evidence that the
      interaction between noise and dynamics plays an important functional role in
      shaping key brain processes. In particular, we discuss a unifying theoretical
      framework that explains how structured spatio-temporal resting state patterns
      emerge from noise driven explorations of unstable or stable oscillatory states.
      Embracing this perspective, we explore the consequences of network manipulations
      to understand some of the brain's dysfunctions, as well as network effects that
      offer new insights into routes towards therapy, recovery and brain repair. These
      collective insights will be at the core of a new computational environment, the
      Virtual Brain, which will allow flexible incorporation of empirical data
      constraining the brain models to integrate, unify and predict network responses
      to incipient pathological processes.

PMID- 21175009
TI  - Data warehousing methods and processing infrastructure for brain recovery
      research.
AB  - In order to accelerate translational neuroscience with the goal of improving
      clinical care it has become important to support rapid accumulation and analysis
      of large, heterogeneous neuroimaging samples and their metadata from both normal
      control and patient groups. We propose a multi-centre, multinational approach to
      accelerate the data mining of large samples and facilitate data-led clinical
      translation of neuroimaging results in stroke. Such data-driven approaches are
      likely to have an early impact on clinically relevant brain recovery while we
      simultaneously pursue the much more challenging model-based approaches that
      depend on a deep understanding of the complex neural circuitry and physiological
      processes that support brain function and recovery. We present a brief overview
      of three (potentially converging) approaches to neuroimaging data warehousing and
      processing that aim to support these diverse methods for facilitating prediction
      of cognitive and behavioral recovery after stroke, or other types of brain injury
      or disease.

PMID- 21175010
TI  - Virtual brain transplantation (VBT): a method for accurate image registration and
      parcellation in large cortical stroke.
AB  - OBJECTIVE: The objective of the current study was to develop a semi-automated
      method to register and parcellate lesioned brains in a surface space with
      anatomical accuracy, facilitating group-level fMRI analyses in patients with
      large cortical strokes. METHODS: Thirteen chronic patients with a single large
      left hemisphere stroke were included in the study. Our "virtual brain
      transplantation" (VBT) approach is based on pre-processing high resolution
      anatomical T1-weighted brain images by "filling in" the lesion with "transplanted
      virtual tissue" from the non-stroke hemisphere, providing "normal" anatomical
      landmarks for standard alignment and inflation algorithms developed for healthy
      individuals. Biological validation of the approach was performed by quantifying
      in Freesurfer space the areas of 12 hand-drawn sulci found inside and outside the
      stroke following "transplantation". RESULTS: Our results show no difference in
      the Freesurfer parcellation of 12 different regions when comparing a lesioned
      hemisphere with the non-lesioned hemisphere, attesting for the validity of the
      anatomical classification in the stroke hemisphere. As consequence of the
      anatomical precision, this method permits a more detailed and quantifiable
      anatomical description of the regions affected directly by the stroke.
      CONCLUSIONS: This method permits accurate surface reconstruction of the injured
      hemisphere after stroke by making it possible to extract the cortical surface
      from these images and to utilize this in software modules (FreeSurfer)
      specialized for aligning cortical surfaces using high-dimensionality warping
      algorithms. In addition, it permits quantifying, within bounds, the extent to
      which the lesion in question is associated with damage to particular regions of
      the cortical surface, information that is of explanatory value in models that
      attempt to explain brain-behavior relations using lesion analysis.

PMID- 21175011
TI  - Lesion sites that predict the ability to gesture how an object is used.
AB  - We used a two stage procedure to predict which stroke patients would have chronic
      difficulties gesturing how to use an object when object recognition and hand
      movements were intact. First, we searched our PLORAS database by behavior and
      identified 5 patients who had chronic difficulty gesturing object use but no
      difficulty recognising objects, comprehending words or moving their hands. High
      definition lesion analyses showed that all 5 patients had damage to the white
      matter underlying the left ventral supramarginal gyrus, (A) close to the cortex,
      (B) deep towards the midline and (C) extending into the temporal lobe. In
      addition, 2 patients had damage to (D) the left posterior middle temporal cortex,
      and 3 patients had damage to (E) the left dorsal supramarginal gyrus and (F) the
      left premotor cortex. Second, we searched our database by lesion location for
      patients who had damage to any part of regions ABCDEF. The incidence of gesturing
      difficulties was higher in patients with damage to ABCD (7/9), ABCE (7/10) or
      ABCDE (10/13) than ABCF (7/13), ABC (8/16) or partial damage to ABCF (6/32). Thus
      behaviour was best predicted by the combination of regions that were damaged (a
      "network-lesion") rather than on the basis of each region alone or overall lesion
      size. Our results identify which parts of the temporal and parietal lobes impair
      the ability to gesture object use and which parts need to be intact to support it
      after damage. Our methods provide a framework for future studies aiming to
      predict the consequences of brain damage.

PMID- 21175012
TI  - Functional connectivity metrics during stroke recovery.
AB  - We explore functional connectivity in nine subjects measured with 1.5T fMRI-BOLD
      in a longitudinal study of recovery from unilateral stroke affecting the motor
      area (Small et al., 2002). We found that several measures of complexity of
      covariance matrices show strong correlations with behavioral measures of
      recovery. In Schmah et al. (2010), we applied Linear and Quadratic Discriminants
      (LD and QD) computed on a principal components (PC) subspace to classify the fMRI
      volumes into "early" and "late" sessions. We demonstrated excellent
      classification accuracy with QD but not LD, indicating that potentially important
      differences in functional connectivity exist between the early and late sessions.
      Motivated by Mclntosh et al. (2008), who showed that EEG brain-signal variability
      and behavioral performance both increased with age during development, we
      investigated complexity of the covariance matrix for this longitudinal stroke
      recovery data set. We used three complexity measures: the sphericity index
      described by Abdi (2010); "unsupervised dimensionality", which is the number of
      PCs that minimizes unsupervised generalization error of a covariance matrix
      (Hansen et al., 1999); and "QD dimensionality", which is the number of PCs that
      minimizes the classification accuracy of QD. Although these approaches measure
      different kinds of complexity, all showed strong correlations with one or more
      behavioral tests: nine-hole peg test, hand grip test and pinch test. We could not
      demonstrate that either sphericity or unsupervised dimensionality were
      significantly different for the "early" and "late" sessions using a paired
      Wilcoxon test. However, the amount of relative behavioral improvement was
      correlated with sphericity of the overall covariance matrix (pooled across all
      sessions), as well as with the divergence of the eigenspectra between the "early"
      and "late" covariance matrices. Complexity measures that use the number of PCs
      (which optimize QD classification or unsupervised generalization) were correlated
      with the behavioral performance of the final session, but not with the relative
      improvement. These are suggestive, but limited, results given the sample size,
      restricted behavioral measurements and older 1.5T BOLD data sets. Nevertheless,
      they indicate one potentially fruitful direction for future data-driven fMRI
      studies of stroke recovery in larger, better-characterized longitudinal stroke
      data sets recorded at higher field strength. Finally, we produced sensitivity
      maps (Kjems et al., 2002) corresponding to both linear and quadratic
      discriminants for the "early" vs. "late" classification. These maps measure the
      influence of each voxel on the class assignments for a given classifier.
      Differences between the scaled sensitivity maps for the linear and quadratic
      discriminants indicate brain regions involved in changes in functional
      connectivity. These regions are highly variable across subjects, but include the
      cerebellum and the motor area contralateral to the lesion.

PMID- 21175013
TI  - Non-fluent aphasia and neural reorganization after speech therapy: insights from
      human sleep electrophysiology and functional magnetic resonance imaging.
AB  - Stroke is associated with long-term functional deficits. Behavioral interventions
      are often effective in promoting functional recovery and plastic changes. Recent
      studies in normal subjects have shown that sleep, and particularly slow wave
      activity (SWA), is tied to local brain plasticity and may be used as a sensitive
      marker of local cortical reorganization after stroke. In a pilot study, we
      assessed the local changes induced by a single exposure to a therapeutic session
      of IMITATE (Intensive Mouth Imitation and Talking for Aphasia Therapeutic
      Effects), a behavioral therapy used for recovery in patients with post-stroke
      aphasia. In addition, we measured brain activity changes with functional magnetic
      resonance imaging (fMRI) in a language observation task before, during and after
      the full IMITATE rehabilitative program. Speech production improved both after a
      single exposure and the full therapy program as measured by the Western Aphasia
      Battery (WAB) Repetition subscale. We found that IMITATE induced reorganization
      in functionally-connected, speech-relevant areas in the left hemisphere. These
      preliminary results suggest that sleep hd-EEGs, and the topographical analysis of
      SWA parameters, are well suited to investigate brain plastic changes underpinning
      functional recovery in neurological disorders.

PMID- 21175014
TI  - Attention modulation regulates both motor and non-motor performance: a high
      density EEG study in Parkinson's disease.
AB  - We have previously shown that, in early stages of Parkinson's disease (PD),
      patients with higher reaction times are also more impaired in visual sequence
      learning, suggesting that movement preparation shares resources with the learning
      of visuospatial sequences. Here, we ascertained whether, in patients with PD, the
      pattern of the neural correlates of attentional processes of movement planning
      predict sequence learning and working memory abilities. High density
      Electroencephalography (EEG, 256 electrodes) was recorded in 19 patients with PD
      performing reaching movements in a choice reaction time paradigm. Patients were
      also tested with Digit Span and performed a visuomotor sequence learning task
      that has an important declarative learning component. We found that attenuation
      of alpha/beta oscillatory activity before the stimulus presentation in
      frontoparietal regions significantly correlated with reaction time in the choice
      reaction time task, similarly to what we had previously found in normal subjects.
      In addition, such activity significantly predicted the declarative indices of
      sequence learning and the scores in the Digit Span task. These findings suggest
      that some motor and non motor PD signs might have common neural bases, and thus,
      might have a similar response to the same behavioral therapy. In addition, these
      results might help in designing and testing the efficacy of novel rehabilitative
      approaches to improve specific aspects of motor performance in PD and other
      neurological disorders.

PMID- 21175015
TI  - Hippocampal signal complexity in mesial temporal lobe epilepsy: a noisy brain is
      a healthy brain.
AB  - Patients with mesial temporal lobe epilepsy (mTLE) show structural and functional
      abnormalities in hippocampus and surrounding mesial temporal structures. Brain
      signal complexity appears to be a marker of functional integrity or capacity. We
      examined complexity in 8 patients with intracranial hippocampal electrodes during
      performance of memory tasks (scene encoding and recognition) known to be
      sensitive to mesial temporal integrity. Our patients were shown to have right
      mesial temporal seizure onsets, permitting us to evaluate both epileptogenic
      (right) and healthy (left) hippocampi. Using multiscale entropy (MSE) as a
      measure of complexity, we found that iEEG from the epileptogenic hippocampus
      showed less complexity than iEEG from the healthy hippocampus. This difference
      was reliable for encoding but not for recognition. Our results indicate that both
      functional integrity and cognitive demands influence hippocampal signal
      complexity.

PMID- 21175016
TI  - Information integration: its relevance to brain function and consciousness.
AB  - A proper understanding of cognitive functions cannot be achieved without an
      understanding of consciousness, both at the empirical and at the theoretical
      level. This paper argues that consciousness has to do with a system's capacity
      for information integration. In this approach, every causal mechanism capable of
      choosing among alternatives generates information, and information is integrated
      to the extent that it is generated by a system above and beyond its parts. The
      set of integrated informational relationships generated by a complex of
      mechanisms--its quale--specify both the quantity and the quality of experience.
      As argued below, depending on the causal structure of a system, information
      integration can reach a maximum value at a particular spatial and temporal grain
      size. It is also argued that changes in information integration reflect a
      system's ability to match the causal structure of the world, both on the input
      and the output side. After a brief review suggesting that this approach is
      consistent with several experimental and clinical observations, the paper
      concludes with some prospective remarks about the relevance of understanding
      information integration for analyzing cognitive function, both normal and
      pathological.

PMID- 21175017
TI  - The development of a noisy brain.
AB  - Early in life, brain development carries with it a large number of structural
      changes that impact the functional interactions of distributed neuronal networks.
      Such changes enhance information processing capacity, moving the brain from a
      deterministic system to one that is more stochastic. The evidence from empirical
      studies with EEG and functional MRI suggests that this stochastic property is a
      result of an increased number of possible functional network configurations for a
      given situation. This is captured in the variability of endogenous and evoked
      responses or "brain noise ". In empirical data from infants and children, brain
      noise increases with maturation and correlates positively with stable behavior
      and accuracy. The noise increase is best explained through increased noise from
      network level interactions with a concomitant decrease of local noise. In old
      adults, brain noise continues to change, although the pattern of changes is not
      as global as in early development. The relation between high brain noise and
      stable behavior is maintained, but the relationships differ by region, suggesting
      changes in local dynamics that then impact potential network configurations.
      These data, when considered in concert with our extant modeling work, suggest
      that maturational changes in brain noise represent the enhancement offunctional
      network potential--the brain's dynamic repertoire.

PMID- 21175018
TI  - Indirect bonding--do custom bases need a plastic conditioner? A randomised
      clinical trial.
AB  - AIM: To compare the clinical failure rates over six months of indirectly bonded
      brackets with and without methyl methacrylate monomer (MMM) conditioned custom
      bases. METHODS: Thirty-six consecutive patients satisfying the selection criteria
      were randomly assigned to two groups in a split-mouth study design. In Group 1,
      the maxillary right and mandibular left quadrants were indirectly bonded after
      the custom bases had been conditioned with MMM. The brackets bonded to the teeth
      in the contralateral quadrants were not conditioned. In Group 2, the custom bases
      on the brackets indirectly bonded to the teeth in the maxillary left and
      mandibular right quadrants were conditioned and the brackets in the contralateral
      quadrants were not conditioned. Over the 6-month observation period all loose
      brackets were recorded, and the data were compared with a Wilcoxon signed ranks
      test. RESULTS: Of the 828 brackets placed, six with the MMM conditioning came
      loose (1.4 per cent failed) compared with five in the Control group (1.2 per cent
      failed). The difference was not statistically significant (p = 0.74). CONCLUSION:
      These results indicate that conditioning custom bases with methyl methacrylate
      monomer is an unnecessary step when indirectly bonding brackets.

PMID- 21175019
TI  - The effect of morphine on orthodontic tooth movement in rats.
AB  - OBJECTIVES: To investigate the effect of morphine as an exogenous opioid on
      orthodontic tooth movement. Naltrexone will be used as an opioid antagonist to
      confirm the results. METHODS: Forty rats were randomly divided into four equal
      groups. The first group received no injection; the second group received daily
      injections of morphine; the third group received daily naltrexone-morphine
      injections and the fourth group daily injections of naltrexone-normal saline. The
      left first maxillary molar in each rat was tipped mesially with a NiTi closed
      coil spring. The rats were sacrificed after 14 days and the maxillae fixed,
      sectioned serially and examined histologically. RESULTS: The greatest amount of
      tooth movement occurred in the Control group and the least amount of tooth
      movement in the Morphine group. Tooth movement in the Morphine group was
      significantly different from the other three groups (p < 0.05). The differences
      in tooth movement in the Control, Morphine-naltrexone and Naltrexonesaline groups
      were not statistically significant (p > 0.05). No statistically significant
      histological differences were found. CONCLUSIONS: Morphine reduced orthodontic
      tooth movement in rats. This effect was reversed by the opioid antagonist,
      naltrexone, which had no effect on tooth movement.

PMID- 21175020
TI  - Initial and fatigue bond strengths of chromatic and light-cured adhesives.
AB  - AIM: To compare the initial and fatigue shear bond strengths of a chromatic
      adhesive with a light-cured adhesive in an ex vivo laboratory study. METHODS:
      Hydroxyapatite discs were used as the bonding substrate. They were produced by
      cold uni-axial compression at 20 tons, sintered at 1300 degrees C and embedded in
      epoxy resin before grinding and polishing. One hundred and fifty upper left
      central incisor brackets were bonded to the discs with Transbond PLUS Color
      Change (3M Unitek, Monrovia, CA, USA) while another 150 similar brackets were
      bonded with Transbond XT (3M Unitek, Monrovia, CA, USA). Seventy-five brackets
      from each group were subjected to cyclic loading (5000 cycles at 2 Hz) at 50 per
      cent of the mean bond strength in a Dartec Series HC 10 Testing Machine. Initial
      (unfatigued) and fatigued bond strengths were determined by applying a shear
      force at the bracket-substrate interface using a custom-made metal jig in an
      Instron Universal Testing Machine. One-way ANOVA with Bonferroni post-hoc
      correction and two-way ANOVA were used to analyse the differences between the
      initial and fatigue mean shear bond strengths of the adhesives. The survival and
      bond reliability of both adhesives were evaluated with the Kaplan-Meier and Cox
      regression analyses. RESULTS: The initial mean shear bond strength for Transbond
      PLUS Color Change (16.72 MPa) was higher than Transbond XT (15.11 MPa), but this
      was not statistically significant (p = 0.109). The fatigue mean shear bond
      strength for Transbond XT (15.87 MPa) was similar to that of Transbond PLUS Color
      Change (15.33 MPa), and the difference was not statistically significant (p >
      0.999). There were no significant differences when the effects of the material (p
      = 0.264) or fatiguing (p = 0.512) were considered separately, but in combination,
      the effect on bond strength was statistically significant (p = 0.026). The
      survival analysis showed that both adhesives demonstrated similar survival
      patterns in the unfatigued and fatigued states. Analysis of the material type and
      fatiguing showed no effect on the survival pattern for both adhesives (p =
      0.098). CONCLUSIONS: There were no statistically significant differences between
      the mean initial (unfatigued) and fatigue bond strengths of Transbond XT and
      Transbond PLUS Color Change under laboratory conditions. A survival analysis for
      both resins with and without fatigue loading exhibited similar behaviour with
      respect to their survival patterns. Although this may imply that under clinical
      conditions the two adhesives could behave similarly, the clinical extrapolation
      of these results should be interpreted with caution.

PMID- 21175021
TI  - A comparative assessment of the forces and moments generated at the maxillary
      incisors between conventional and self-ligating brackets using a reverse curve of
      Spee NiTi archwire.
AB  - OBJECTIVES: To compare the intrusive forces and labio-palatal moments generated
      at the maxillary incisors by a 0.017 x 0.025 inch reverse curve NiTi wire using
      self-ligating and conventional brackets. METHODS: Ten 0.017 x 0.025 inch reverse
      curve NiTi archwires were used with each of the following 0.022 inch bracket
      systems: Titanium Ortho (Ormco/Sybron, CA, USA), In-Ovation R (GAC International,
      NY, USA) and Damon System 3MX (Ormco/Sybron, CA, USA). The wires were inserted on
      bracketed maxillary Frasaco models, with segmented maxillary incisors. Simulated
      intrusion from 0.0-1.0 mm was performed on the Orthodontic Measurement and
      Simulation System, which recorded the intrusive forces and the labio-palatal
      moments at 0.05 mm increments. The data were analysed with the ANOVA and Scheffe
      tests. RESULTS: The intrusive forces were significantly different between all
      bracket types. The highest force was recorded with the conventional Titanium
      Orthos brackets (8.2 N), followed by the Damon 3MX brackets (6.3 N) and the In
      Ovation R brackets (5.5 N). The moments were found to be significantly different
      between the conventional and the self-ligating brackets, but not between the two
      types of self-ligating brackets. The highest moments were recorded with the self
      ligating brackets (16.6-16.9 N/mm), followed by the conventional brackets (10.8
      N/mm). CONCLUSIONS: The intrusive forces exerted on the maxillary incisors by a
      0.017 x 0.025 inch reverse curve NiTi archwire during the final 1 mm of levelling
      are very high and beyond the necessary intrusive force level for these teeth.
      Lower intrusive forces, but higher labio-palatal moments, were recorded with the
      self-ligating brackets.

PMID- 21175022
TI  - Bond strengths and debonding characteristics of two types of polycrystalline
      ceramic brackets.
AB  - OBJECTIVES: To compare the shear bond strengths and modes of failure of three
      orthodontic brackets: a polycrystalline ceramic bracket, a collapsible
      polycrystalline ceramic bracket and a metal bracket. METHODS: Ninety extracted
      human premolar teeth were selected and examined at x3 magnification for any
      enamel defects. Three types of brackets and one orthodontic adhesive were used.
      One half of the sample was tested in a universal testing machine to determine the
      shear bond strength. The other half was debonded with the appropriate pliers and
      the tooth surface examined at x5 magnification. The site of failure was scored
      with the modified Adhesive Remnant Index (ARI). Teeth with an ARI grade of zero
      were examined in a SEM to determine any enamel fracture. RESULTS: No
      statistically significant differences in bond strength among the samples were
      found (p > 0.159). The modes of failure after debonding with pliers were
      predominantly at the bracket-adhesive interface. The mean shear bond strength of
      the Clarity bracket was 10.78 +/- 2.74 MPa, the InVu bracket was 12.43 +/- 2.40
      MPa and the metal bracket was 11.89 +/- 1.83 MPa. There were significant
      differences in the mean rank of the ARI grade between the three groups (p =
      0.006). The Clarity and InVu (p = 0.011) and the Clarity and metal brackets (p =
      0.005) were significantly different, but there was no difference between the InVu
      and metal brackets (p = 0.187). CONCLUSIONS: All three samples had similar bond
      strengths. The risk of ceramic fracture on debonding was greatest for the InVu
      ceramic bracket.

PMID- 21175023
TI  - Skeletal and dental changes after rapid maxillary expansion: a computed
      tomography study.
AB  - OBJECTIVES: To investigate the skeletal and dental changes induced by rapid
      maxillary expansion, using computed tomography (CT) scans and three-dimensional
      (3-D) reconstructed images. METHODS: Twenty patients (Mean age: 12.3 +/- 1.9
      years) who required rapid maxillary expansion as a part of their comprehensive
      orthodontic treatment underwent pretreatment (T1) and post-treatment (T2) CT
      scans. The T2--T1 differences between selected skeletal and dental measurements
      on the coronal CT and 3-D volumetric images were compared using the Wilcoxon
      signed ranks test. RESULTS: At T2 the Maxillary alveolar width (4.5 +/- 3.5 mm)
      was greater than the Maxillary base width (1.7 +/- 0.9 mm). The greatest
      transverse dental change was in the Intermolar width (6.3 +/- 2.1 mm and 2.7 +/-
      1.9 mm at the crown and the apex, respectively). On the 3-D volume, significant
      increases occurred in the Bicondylar width (1.2 +/- 1.3 mm), Bimaxillo-mandibular
      width (2.1 +/- 2.3 mm) and the Maxillary width (2.5 +/- 1.6 mm). The greatest
      change in the dental measurements was in the Maxillary first molar width (6.4 +/-
      0.1 mm). The Maxillary central incisor angle decreased significantly (-7.9 +/-
      8.4 mm), indicating an increase in the distance between the apices of the central
      incisors. CONCLUSION: Volumetric 3-D CT scanning provides a useful method for
      assessing skeletal and dental changes after rapid maxillary expansion. Although
      significant increases occurred in most skeletal and dental measures, it appears
      that dental tipping explains most of the expansion.

PMID- 21175024
TI  - Strength of attachment between band and glass ionomer cement.
AB  - AIM: To determine the strength of attachment between plain stainless steel band
      material and glass ionomer cement. METHODS: Seventy-five extracted upper
      premolars, free of visible structural defects, were used. The teeth were divided
      randomly into three groups and embedded in acrylic resin blocks. A short length
      of plain, stainless steel band material with a welded stainless steel standard
      edgewise 0.022 inch bracket was adapted to the buccal surface of each tooth. The
      bracket-stainless steel pads were then cemented to the teeth with either Bandtite
      (Group 1), Granitec (Group 2) or Ariadent (Group 3) glass ionomer cement and
      stored in an incubator at 37 degrees C for 30 days. The shear bond strengths of
      the specimens were measured and compared. RESULTS: The mean shear bond strengths
      (SBS) were significantly different: Bandtite 0.7331 +/- 0.056 Mpa; Granitec
      0.3869 +/- 0.047 Mpa; Ariadent 0.2931 +/- 0.033 Mpa (ANOVA, p < 0.001). Tukey HSD
      post-hoc tests also showed significant differences between Bandtite and Granitec,
      Bandtite and Ariadent, and Granitec and Ariadent (p < 0.001). All specimens
      failed at the band-cement interface. CONCLUSION: The highest and lowest SBS were
      related to Bandtite and Ariadent cements, respectively. All cements had bond
      strengths less than the range of bond strengths considered to be clinically
      acceptable for bonded orthodontic attachments. Mechanical factors are important
      for band retention.

PMID- 21175025
TI  - Lip-tooth relationships during smiling and speech: an evaluation of different
      malocclusion types.
AB  - BACKGROUND: Few studies have focused on the impact of malocclusion on lip - tooth
      relationships during smiling and speech. AIM: To evaluate the impact of different
      malocclusions on lip - tooth relationships during smiling and speech, using video
      images. METHODS: One hundred and three subjects with Class I (N = 31), Class II
      division 1 (N = 26), Class II division 2 (N = 16) and Class III malocclusions (N
      = 30) were asked to repeat the same sentence and then smile in front of a video
      camera. Nine frames were extracted from each subject's video clip: at rest, posed
      smile, unposed smile and during the pronunciation of the sounds: 'che', 'fa',
      'se', 'chee', 'tee' and 'mee'. On each frame, up to 10 parameters describing the
      lip - tooth relationships were measured. RESULTS: In all frames, there were no
      statistically significant differences in the upper central incisor display ratios
      among the malocclusion groups (p > 0.05). The buccal corridor ratio in the posed
      and unposed smiles did not differ significantly among the malocclusions (p >
      0.05). The most frequently visible last maxillary tooth was the first premolar in
      the posed smile, and the second premolar in the unposed smile. In each
      malocclusion group, the upper central incisor display ratio varied significantly
      among the nine frames and the buccal corridor ratio during the unposed smile was
      less than the ratio during the posed smile; although this was only significant in
      the Class II division 2 subjects. The smile arc was similar in all malocclusions.
      CONCLUSIONS: In each malocclusion the upper central incisor display ratio varied
      significantly among the nine frames. In each group, the buccal corridor ratio
      during the unposed smile was less than that during the posed smile, but only the
      Class II division 2 group was significantly different. The smile arc did not
      differ among the malocclusions.

PMID- 21175026
TI  - Effects of orthodontic treatment and premolar extractions on the mandibular third
      molars.
AB  - BACKGROUND: The space available for an unerupted mandibular third may depend on
      the choice of premolar extracted. AIMS: To investigate the effects of orthodontic
      treatment and premolar extractions on the inclinations of the mandibular third
      molars and the space available for their eruption, and to compare these changes
      with a nonextraction group. METHODS: The pre- and post-treatment panoramic
      radiographs of 54 subjects (20 males, 34 females) were used. Eighteen of these
      subjects had the four first premolars extracted, 16 subjects had four second
      premolars extracted and 20 subjects were treated nonextraction. Changes in the
      inclinations and spaces available for the unerupted third molars were compared.
      RESULTS: In the nonextraction group the third molars uprighted approximately 1
      degree and in the second premolar extraction group the third molars uprighted 10
      degrees. The spaces available for the third molars increased significantly in the
      first and second premolar extraction groups as compared with the space available
      in the nonextraction group. CONCLUSIONS: Orthodontic treatment and extraction of
      the second premolars improved the inclinations of unerupted third molars and the
      space available for their eruption into the arch. The changes in inclination and
      eruption space were less marked following first premolar extractions.

PMID- 21175027
TI  - Cephalometric analysis of Malay children with and without unilateral cleft lip
      and palate.
AB  - OBJECTIVE: To investigate the craniofacial morphology of Malay children with
      repaired UCLP and compare the data with non-cleft Malay children. METHODS: Twenty
      Malay children with repaired UCLP (12 boys, 8 girls; Mean age: 10.5 years) and 20
      normal Malay children (8 boys, 12 girls; Mean age: 9.72 years) were recruited
      from the Combined Cleft Lip and Palate Clinic and the Department of Children's
      Dentistry and Orthodontics, Faculty of Dentistry, University of Malaya, Malaysia.
      Lateral cephalometric radiographs were taken with the head orientated parallel to
      the floor. Thirty-one linear and angular variables were measured on the lateral
      cephalometric radiographs with Dolphin Imaging Software Version 10.0 (Dolphin
      Imaging, Chatsworth, CA, USA). The data were analysed with the Mann-Whitney U
      test and the level of significance was set at p < 0.05. RESULTS: In the UCLP
      group, the girls had deeper overbites than the boys (p = 0.011), and in the
      Control group the girls had a significantly more acute cranial base angle (NSBa,
      p = 0.017) and a less protrusive lower lip (LL-E line, p = 0.21). The data for
      the boys and girls were combined. Subjects in the UCLP group had a more acute
      cranial base angle, shorter and more retruded maxillae and were more skeletal III
      than the subjects in the Control group. In the UCLP group, the upper and lower
      incisors were less proclined than in the Control group, the interincisal angle
      was more obtuse and the overjet reduced by 6 mm. There were no significant facial
      height differences. The nasolabial angle (Col-Sn-UL) was significantly more
      obtuse and the upper lip relative to the E line more retrusive in the UCLP group.
      There was no significant difference between the groups in facial heights or the
      maxillo-mandibular planes angle. CONCLUSION: Malay children with repaired UCLP
      have small, retrusive maxillae. The mandible in this group of children was of
      normal size and position, relative to the cranial base. Pressure from the
      repaired upper lip may be responsible for the retruded maxillae, retroclined
      incisors and obtuse nasolabial angle.

PMID- 21175028
TI  - Factors contributing to stability of protraction facemask treatment of Class III
      malocclusion.
AB  - AIM: To identify the craniofacial characteristics that contribute to long-term
      stability of protraction facemask treatment of Class III malocclusion. METHODS:
      Fifty subjects who met the following criteria were recruited: subjects with an
      anterior crossbite and 'Wits' appraisal < -3.5 mm; subjects who had been
      successfully treated with a protraction facemask (at the end of active
      orthopaedic treatment the overjet was overcorrected by more than 4 mm); the
      facemask treatment was started at either CS1 or CS2 and the subjects were
      followed until CS4; no subject had a congenital craniofacial deformity. Based on
      the occlusal status at CS4, three groups were identified: Stable group (SG),
      Unstable group (USG) and a Failed group (FG). One-way analysis of variance and
      Scheffe's post-hoc multiple comparisons were used to analyse the differences
      between the groups. Stepwise discriminant analysis was used to identify the
      craniofacial characteristics able to predict the stability of protraction
      facemask treatment. RESULTS: There were no statistically significant differences
      between USG and FG. The N-S-Ar was significantly larger and Co-Gn, Wits and LAFH
      significantly smaller in the SG group as compared with the USG and FG groups. The
      critical score between SG and USG was 0.368 and between USG and FG it was -0.981.
      Individuals with scores higher than 0.368 showed relatively stable occlusions at
      CS4, whereas anterior crossbites returned in individuals with scores less than 
      0.981 at CS4. The overall percentage of correctly classified cases was 74 per
      cent, with 90.0 per cent in SG and 73.3 per cent in FG. CONCLUSIONS: A severe
      maxillo-mandibular discrepancy, an increased vertical dimension and a prognathic
      mandible were unfavourable factors for long-term stability following early
      treatment of severe Class III subjects with protraction facemasks.

PMID- 21175029
TI  - Effects of rapid-slow maxillary expansion on the dentofacial structures.
AB  - BACKGROUND: To date, no study has determined if rapid followed by slow maxillary
      expansion (also termed 'semi-rapid' expansion) has the same effects on the
      dentofacial skeleton as rapid maxillary expansion. OBJECTIVE: To determine the
      vertical and sagittal changes in the facial skeleton during and following rapid
      then slow maxillary expansion (R-SME). METHODS: Bonded maxillary expansion
      appliances were used to separate the maxillae over six days by activating the
      midline screws twice a day. The screws were then activated three times a week
      until sufficient expansion was obtained (Mean: 3.4 months) and used as retainers
      for six months. Cephalometric measurements at the start of expansion (T1), end of
      expansion (T2) and end of retention (T3) were compared with paired t-tests.
      Pearson correlation coefficients were used to determine the associations between
      the expansion (dental and skeletal) and the cephalometric changes. RESULTS: The
      maxillae moved forward a small, but statistically significant, extent during
      expansion. The upper molars were extruded and the mandible 'rotated' downward and
      backward. Although the vertical height of the facial skeleton (SN/GoMe, S-Go, N
      Me, ANS-Me) increased significantly during expansion, the changes were small and
      highly variable. Some dimensions (SN/GoMe) relapsed during retention, while
      others (S-Go, N-Me) increased. CONCLUSIONS: Rapid then slow maxillary expansion
      caused a small, but statistically significant, forward movement of the upper
      facial skeleton, a small downward and backward rotation of the mandible and a
      small increase in face height. The changes were similar to those found during
      rapid maxillary expansion.

PMID- 21175030
TI  - Shear bond strengths of buccal tubes.
AB  - AIMS: To investigate the shear bond strengths of buccal tubes and to determine
      the sites of failure. METHOD: Four orthodontic buccal tubes were selected: A,
      American Orthodontics; B, 3M Unitek - small base; C, 3M Unitek--large base; D,
      Hangzhou Dentop. Twenty buccal tubes from each group were bonded to the buccal
      surfaces of lower right first molars with the same light-cured composite resin.
      The buccal tubes were debonded with a universal testing machine and the data
      analysed. The amount of adhesive remaining on the teeth after debonding was
      classified with the modified adhesive remnant index (ARI). RESULTS: The groups
      ranked from the highest to lowest bond strength (MPa) were: B, A, D and C. The
      bond strengths of the buccal tubes, except Groups A and B, were significantly
      different (p < 0.05). The majority of the buccal tubes (63 per cent) had modified
      ARI scores of 1 and 2 and 25 per cent of the tubes had scores of 4 and 5. After
      debonding, no adhesive remained on 40 per cent of the teeth in Groups B and D.
      CONCLUSIONS: The shear bond strengths of the buccal tubes fell below the value
      considered to be clinically acceptable. There were no differences between the
      shear bond strengths of the buccal tubes with photoetched and microetched bases.
      The buccal tubes with the largest base failed prematurely, possibly because the
      unsupported bonding pad flexed during debonding.

PMID- 21175031
TI  - The effect of a Clark twin block on mandibular motion: a case report.
AB  - AIMS: To investigate mandibular motion in six degrees of freedom before, during
      and after twin block treatment in one individual. METHODS: The appliance was worn
      for eight months, and motion recordings, using a 12-camera opto-electric system,
      were captured prior to placement of a twin block appliance and 2, 4, 14 and 52
      weeks after insertion. RESULTS: The wide variations in mandibular motion that
      accompany twin block wear disappeared post-treatment, except for an increase in
      anteroposterior movement of the mandible. CONCLUSION: Twin block therapy appears
      to affect mandibular motion temporarily.

PMID- 21175032
TI  - Orthodontic treatment of a transmigrated mandibular canine: a case report.
AB  - BACKGROUND: Intraosseous migration of a lower canine across the midline is a rare
      dental anomaly. The treatment options include: forced eruption of the unerupted
      tooth using orthodontic traction, autotransplantation, extraction followed by
      prosthetic replacement. AIM: To report the management of a transmigrated lower
      right canine. METHOD: The treatment involved surgical, orthodontic and cosmetic
      dental treatment. No permanent teeth were extracted. RESULTS: The transmigrated
      canine was placed between the left central and lateral incisors and the crown
      recontoured to simulate a lateral incisor. An acceptable aesthetic and functional
      outcome was gained. CONCLUSION: Transmigration is a rare dental condition that
      can be treated successfully with a collaborative effort from several dental
      disciplines.

PMID- 21175033
TI  - Non-surgical treatment of mandibular deviation: a case report.
AB  - BACKGROUND: Mandibular deviation due to premature contact of teeth in crossbite
      may be associated with facial asymmetry. AIM: To describe the non-surgical
      treatment of mandibular deviation associated with a marked facial asymmetry.
      METHODS: A 13.5 year-old girl presented with a unilateral posterior crossbite,
      noticeable facial asymmetry, anterior crossbite and displacement of the mandible
      on closure. She had no history of head injury or significant medical problems and
      her parents rejected surgical correction. A removable appliance was used to
      correct the crossbite followed by fixed appliances to complete treatment.
      RESULTS: Treatment resulted in a marked improvement in facial symmetry and
      elimination of the mandibular displacement. CONCLUSIONS: Early correction of a
      functional deviation associated with a unilateral facial asymmetry may avoid the
      need for surgery.

PMID- 21175034
TI  - Effective orthodontics.

PMID- 21175035
TI  - Optimal force.

PMID- 21175036
TI  - Prevention of sodium valproate-induced hepatotoxicity by curcumin, rosiglitazone
      and N-acetylcysteine in rats.
AB  - The present study was designed to examine the potential preventive effect of
      curcumin (CMN; CAS 458-37-7), rosiglitazone (RGN; CAS 155141-29-0), N
      acetylcysteine (NAC; CAS 616-91-1), resveratrol (RSV; CAS 501-36-0), and losartan
      (LOS; CAS 114798-26-4) on sodium valproate-induced hepatotoxicity. Sodium
      valproate (SVP; CAS 1069-66-5) was given at a dose of 250 mg/kg i. p. 3 times
      daily for one week. The tested compounds were given simultaneously with SVP for
      one week. The results demonstrate that CMN, RGN and NAC treatment can confer
      protection from SVP-induced hepatotoxicity. The second part of the study includes
      an evaluation of the effect of CMN, RGN and NAC on the anticonvulsant activity of
      SVP against pentetrazole-induced seizures in mice. The results demonstrate that
      CMN, RGN and NAC do not affect the anticonvulsant activity of SVP. Combined
      administration of either of CMN, RGN and NAC with valproate appears to be
      beneficial in reducing valproate-induced hepatotoxicity.

PMID- 21175037
TI  - Quantification of quetiapine in human plasma by reverse phase high performance
      liquid chromatography.
AB  - The objective of the present investigation is to develop and validate a simple,
      economical and reliable high performance liquid chromatography method for the
      quantification of quetiapine (CAS 111974-72-2) in human plasma with a
      quantification limit sufficiently low to support pharmacokinetic studies.
      Imipramine hydrochloride (CAS 113-52-0) was used as internal standard. The
      validated method allows quantification of quetiapine in 15-1000 ng/mL. The method
      was shown to be precise (< 7% coefficient of variation, CV) and accurate (< or =
      10% relative error, RE). The correlation coefficient for quetiapine was > 0.9970.
      The simplicity of the assay and rapid liquid-liquid extraction make it an
      attractive procedure in high-throughput bioanalysis of quetiapine.

PMID- 21175038
TI  - Study of sodium tanshinone II A sulfonate tissue distribution in rat by liquid
      chromatography/tandem mass spectrometry.
AB  - A rapid and sensitive method based on liquid chromatography/tandem mass
      spectrometry (LC-MS/MS) has been developed and fully validated for the
      quantitative determination of sodium tanshinone IIA sulfonate (STS, sodium (1,6,6
      trimethyl-10,11-dioxo-7,8,9-trihydrophenanthro[1,2-b]furan)-yl-2-sulfonate) in
      rat biosamples including plasma and different tissues using sodium tanshinone I
      sulfonate (sodium (1,6-dimethyl-10,11-dioxo-phenanthro[1,2-b]furan)-yl-2
      sulfonate) as internal standard. Simple protein precipitation by acetonitrile was
      utilized for extracting STS from the rat biosamples. Chromatographic separation
      of the sample matrix from the analyte and the internal standard was performed
      using a commercially available analytical column with a mobile phase consisting
      of methanol-5 mmoL/L ammonia acetate (70:30, v/v) at a flow rate of 0.2 mL/min.
      Detection was performed on a triple quadrupole tandem mass spectrometer equipped
      with an electrospray ionization source and operated in the negative-ion mode. The
      intra- and inter-day precisions (RSD%) and deviations of the assay accuracies
      were within 10.0% for STS. The extraction recovery of STS was more than 86.5%.
      The limit of detection (LOD) of STS was 1.0 ng/mL. The method was successfully
      applied to the tissue distribution study of STS intravenously administered to
      healthy Sprague-Dawley rats. The tissue distribution results showed that liver,
      kidney, lung, small intestine and duodenum were the major distribution tissues of
      STS in rats, and that STS had difficulty in crossing the blood-brain barrier.
      After 24 h, STS could be detected only in the kidney, stomach and small
      intestine, indicating that there was no long-term accumulation of STS in rat.

PMID- 21175039
TI  - Species difference in the in vitro and in vivo metabolism of amtolmetin guacil.
AB  - Tolmetin (TMT, CAS 26171-23-3) is a non-steroidal anti-inflammatory drug (NSAID)
      indicated for the relief of signs and symptoms of osteoarthritis, rheumatoid
      arthritis and juvenile rheumatoid arthritis. As TMT causes gastro-intestinal side
      effects like other NSAIDs, its nonacidic prodrug amtolmetin guacil (AMG, CAS
      87344-06-7) was synthesized. AMG has similar NSAID properties like TMT with
      additional gastroprotective property. The aim of this study was to investigate
      whether TMT and AMG are differentially metabolised in rat and human plasma (fresh
      and acidified) and liver microsomes. TMT was found to be stable in all the
      matrices tested viz., rat and human plasma (fresh and acidified) and liver
      microsomes. AMG was found to be stable only in acidified rat and human plasma. On
      the contrary, in fresh human plasma and human liver microsomes AMG was rapidly
      converted to two metabolites, which were subsequently identified as MED5 and MED5
      methyl ester, without yielding any intact TMT. However, in rat fresh plasma and
      liver microsomes, AMG formed MED5 (predominant) and TMT. To corroborate the in
      vitro findings, in vivo pharmacokinetics (PK) studies were done following
      separate dosing of AMG in both rats and humans. In rats, the PK data
      substantiated that following oral administration of AMG it will be converted to
      TMT resulting in similar PK parameters observed for TMT when it was administered
      alone. In humans, however, AMG yields low levels of TMT which substantes the in
      vitro results. Levels of AMG were not detectable in the plasma. These results
      confirm the species differences in the in vitro and in vivo metabolism and
      disposition of AMG. More research work to further explore and understand AMG
      metabolism in humans is required.

PMID- 21175040
TI  - Inhibitory activity of thymol on native and mature Gardnerella vaginalis
      biofilms: in vitro study.
AB  - Bacterial vaginosis (BV) is the most frequent diagnosis made in women with lower
      genital tract symptoms. It has recently been observed that 90 % of subjects with
      BV show the growth of bacteria in the form of biofilms as against only 10%
      without BV, and that Gardnerella vaginalis was the predominant species. The
      propensity of G. vaginalis to form biofilm is clinically relevant because this
      form of growth allows it to tolerate higher concentrations of certain
      antibiotics, thus increasing the possibilty of recurrent BV even after apparently
      curative therapy. The aim of this study was to investigate whether thymol (CAS 89
      83-8), a molecule present in thyme essential oil, that is credited with having a
      series of pharmacological properties including antimicrobial and antifungal
      effects, can interfere with newly formed and mature G. vaginalis biofilms. The
      ability of G. vaginalis ATCC 49145 and two G. vaginalis strains isolated from
      human BV to form biofilm in flat-bottomed 96-well microtitre plates was verified,
      and the effects of thymol concentrations ranging from 1 to 1/16 MIC (minimum
      inhibitory concentration) on preformed and mature biofilms was investigated by
      means of spectrophotometric analysis, Nomarski interference contrast microscopy,
      and fluorescence microscopy with live-dead cell visualisation (SYTO 9 and
      propidium iodide). Native biofilm was inhibited by concentrations ranging from 1
      MIC to 1/8 MIC (32.77% +/- 2.37 to 11.39% +/- 1.46), and mature biofilm was
      inhibited by concentrations ranging from 1 MIC to 1/4 MIC (26.18% +/- 1.36 to
      13.20% +/- 1.44). Nomarski interference contrast and fluorescence microscopy
      visually confirmed these findings. As biofilm is a multi-factorial phenomenon,
      the multiple mechanisms of thymol may act on different steps in the evolution of
      mature biofilm.

PMID- 21175041
TI  - Effects of oral administration of synthesized delta-amides of eflornithine in the
      rat.
AB  - The purpose of this study was to synthesize a series of delta-amide derivatives
      of the antitrypanosomal drug eflornithine (2,5-diamino-2
      (difluoromethyl)pentanoic acid hydrochloride, DMFO, CAS 70052-12-9), to determine
      their physicochemical properties and to assess whether they convert to
      eflornithine in vivo and if so, whether higher systemic exposure to eflornithine
      could be achieved by increase intestinal absorption, suggesting an oral treatment
      to be possible. The derivatives were synthesized by amidation of eflornithine on
      its delta-amino group using acyl chlorides. The partition coefficients (log D, pH
      = 7.4) were found to be between -0.78 +/- 1.07 and -0.07 +/- 1.08 while the
      aqueous solubility (Sw), which as determined in phosphate buffered solution (pH
      7.4), ranged from 11.13 +/- 0.32 to 28.74 +/- 0.36 mg/mL. The synthesized
      compounds were thus mostly more lipophilic than eflornithine itself (log D = 
      0.98 +/- 0.88, Sw = 34.96 +/- 0.37 mg/mL). The intestinal absorption was assessed
      by plasma analysis after oral administration of each compound to Sprague-Dawley
      rats. The biological data revealed that the derivatives were either not absorbed
      from the gastro-intestinal tract or not metabolized into eflornithine as no
      parent drug was detected in the plasma.

PMID- 21175042
TI  - Early history of laboratory breeding of Aedes aegypti (Diptera: Culicidae)
      focusing on the origins and use of selected strains.
AB  - The yellow fever mosquito, Aedes aegypti (L.) (Diptera: Culicidae), is well
      recognized for its extensive adaptation to diverse ecological conditions and for
      genetic variation. Recognizing the importance of strain variation of this
      mosquito, researchers have established a large number of laboratory strains. Some
      of the popular strains have been used for research for years in many laboratories
      around the world. However, the exact origins of many of these strains are
      unknown. In this review, publications and archival records were examined to
      report the early laboratory mosquito rearing practices around the world and to
      identify the origins of selected strains. The records showed that inter
      laboratory sharing of strains was already underway in the early part of the 20th
      century because of the ease of breeding Ae. aegypti and of sending eggs by mail.
      It also was found that the four strains established in major U.S. institutions by
      the mid-1930s, including the "ROCK" (short for Rockefeller) strain, had been
      derived from Cuba, Nigeria, Philippines, or Puerto Rico, all known for a long
      history of transmission of yellow fever virus or dengue virus rather than from
      North America. The strains used for research in Europe were primarily derived
      from West Africa, but strains of Asian, Caribbean, and South American origins
      also were used for comparative experiments among geographic strains. Neglected
      issues related to strain designation and original source identification in
      scientific publications were found and their relevance to current research is
      discussed.

PMID- 21175043
TI  - Study of phlebotomine sand flies (Diptera: Psychodidae) collected in a Leishmania
      endemic area of the metropolitan region of Belo Horizonte, Brazil.
AB  - Phlebotomine sand flies are distributed across nearly all faunal regions of the
      world, represented by over 800 species, of which many are important vectors of
      human pathogens. Brazil is currently faced with the expansion and urbanization of
      leishmaniases, with an increase in the numbers of human cases and seropositive
      dogs in various medium-sized to large cities. The objective of the current study
      was to survey the phlebotomine sand fly species in an area endemic for American
      cutaneous leishmaniasis (ACL) and American visceral leishmaniasis (AVL), i.e.,
      the municipal district of Santa Luzia, lying within the metropolitan region of
      Belo Horizonte in the Brazilian State of Minas Gerais. Sand flies were collected
      monthly in 2004-2005 using modified Falcao light traps hung in the peridomiciles
      of houses and surrounding wooded areas in the district of Baronesa. A total of
      1,552 sand flies belonging to seven species was collected, and an interesting
      pattern of the distribution of the most abundant species relative to the sampling
      locality was revealed. In the wooded areas Lutzomyia whitmani (Antunes &
      Coutinho) predominated, whereas in the urban area Lutzomyia longipalpis (Lutz &
      Neiva) was the most abundant species. These results indicate two possible
      epidemiological patterns of Leishmania transmission in Santa Luzia: one for
      American cutaneous leishmaniasis associated predominantly with wooded areas, and
      another for AVL, with transmission principally occurring around human
      habitations.

PMID- 21175044
TI  - Estimation of dispersal distances of Culex erraticus in a focus of eastern equine
      encephalitis virus in the southeastern United States.
AB  - Patterns of mosquito dispersal are important for predicting the risk of
      transmission of mosquito-borne pathogens to vertebrate hosts. We studied
      dispersal behavior of Culex erraticus (Dyar & Knab), a potentially significant
      vector of eastern equine encephalitis virus (EEEV) that is often associated with
      foci of this pathogen in the southeastern United States. Using data on the
      relative density of resting adult female Cx. erraticus around known emergence
      sites in Tuskegee National Forest, Alabama, we developed a model for the
      exponential decay of the relative density of adult mosquitoes with distance from
      larval habitats through parameterization of dispersal kernels. The mean and 99th
      percentile of dispersal distance for Cx. erraticus estimated from this model were
      0.97 and 3.21 km per gonotrophic cycle, respectively. Parameterized dispersal
      kernels and estimates of the upper percentiles of dispersal distance of this
      species can potentially be used to predict EEEV infection risk in areas
      surrounding the Tuskegee National Forest focus in the event of an EEEV outbreak.
      The model that we develop for estimating the dispersal distance of Cx. erraticus
      from collections of adult mosquitoes could be applicable to other mosquito
      species that emerge from discrete larval sites.

PMID- 21175045
TI  - Effects of temperature and humidity on the survival and water loss of Cimex
      hemipterus (Hemiptera: Cimicidae).
AB  - The effect of temperature and humidity on the survival and water loss of the
      tropical bed bug, Cimex hemipterus (F.), was studied using two field-collected
      strains. Insects were exposed to temperatures ranging from 20 to 45 degrees C and
      relative humidities (RHs) of 33, 75, and 100%. C. hemipterus survived longest
      under the interaction of low temperature (20 degrees C) and high RH (75-100%).
      Survival and water loss were significantly affected (P < 0.01) by temperature and
      RH (either singly, or in interaction). Strain and sex significantly (P < 0.01)
      influenced bed bug survival, but not on water loss. Eggs, first instars, and
      adults reached their upper thermal lethal limit within 1 h at 39 degrees C, 44
      degrees C, and 46 degrees C, respectively. The survival and water loss profiles
      showed that starved C. hemipterus started to die after losing 35-45% of their
      body weights.

PMID- 21175046
TI  - Effect of sublethal dose of diflubenzuron and azadirachtin on various life table
      attributes of Culex quinquefasciatus (Diptera: Culicidae).
AB  - The exposure of sublethal doses (25% emergence inhibition) of diflubenzuron (DFB)
      (0.0002 mg/liter) and azadirachtin (AZD; 0.0079 mg/liter) insect growth
      regulators was provided to late third- early fourth instars of Culex
      quinquefasciatus till emergence of adults to find out the effects on various
      biological and life table attributes of adults, and comparison was made with
      control (CTL) as well. Life expectancy of both males and females of DFB survivors
      was significantly less in comparison with AZD and CTL ones; however, it was
      nonsignificantly different between CTL and AZD. In all treatments, males were
      shorter lived than females of their respective treatments. DFB survivors showed
      significant reduction in number of blood-fed females, resulting in minimum of
      oviposition days, total number of egg rafts, total number of eggs, eggs per egg
      raft, eggs per female life span, and eggs per female per day than survivors of
      both AZD and CTL significantly, but these parameters did not differ significantly
      between CTL and AZD, except eggs per egg raft. The net reproductive rate,
      intrinsic rate of increase, and finite rate of increase were significantly less
      in DFB than rest of the survivors, whereas doubling time for generation was
      significantly high; however, difference in mean generation was not significant
      among them. This study reveals that DFB has the potency to affect severely the
      various life table attributes at sublethal dose, but AZD does not have such
      effectiveness at similar sublethal dose against Cx. quinquefasciatus.

PMID- 21175047
TI  - Distribution of phlebotomine sand flies (Diptera: Psychodidae) in a primary
      forest-crop interface, Salta, Argentina.
AB  - Disordered urbanization and deforestation are the main activities proposed as
      causal factors of re-emergence of American cutaneous leishmaniasis caused by
      Leishmania braziliensis. The purpose of this work was to investigate, in the
      hyperendemic area of Argentina, the distribution of Phlebotomine sand flies at
      the modified primary vegetation-crop interface, as one of the potential sites
      where the effects of changing landscape on sand fly populations may be
      manifested. Twenty samplings were made between June 2004 and August 2005. The
      traps to catch sand flies were set on two consecutive nights every month (except
      in 5 mo, where it became every 15 d). The relationship between sand fly abundance
      and meteorological and landscape variables was analyzed using non-metric
      multidimensional scaling and Kendall's correlation coefficients. Lutzomyia neivai
      (Pinto) was the most abundant species, followed by Lutzomyia migonei (Franca),
      Lutzomyia cortelezzii (Brethes), Lutzomyia shannoni (Dyar), and Lutzomyia
      punctigeniculata (Floch and Abonnenc). Traps located close to modified areas
      collected the greatest numbers of sand flies, whereas traps located in the least
      modified area (adjacent to the primary vegetation) collected the fewest. There
      was a strong negative correlation between the abundance of sand flies and
      precipitation. This study shows that even small modifications in the landscape
      led to an increase in sand fly abundance, mainly Lu. neivai, a Leishmania
      braziliensis vector. This underscores the need for recommendations about the risk
      of American cutaneous leishmaniasis before any environmental intervention is done
      in an endemic area, as well as for the monitoring of sand fly population dynamics
      at the site of intervention, before, during, and after the process.

PMID- 21175048
TI  - Malathion influences competition between Aedes albopictus and Aedes japonicus.
AB  - Competitive interactions may facilitate or repel invaders into new communities,
      and these interactions may depend on other environmental conditions such as the
      presence of pesticides. Malathion is widely used in controlling agricultural
      pests and mosquitoes worldwide. Small amounts of malathion, previously considered
      inconsequential, may in fact increase in lethality when combined with biotic
      stressors in aquatic systems. We tested whether low concentrations of malathion
      (0.11 ppm) that are often detected in aquatic systems, affect competition between
      two invasive mosquito species Aedes albopictus (Skuse) and Aedes japonicus
      Theobald. There were no survivors of Ae. japonicus larvae in malathion. There was
      a significant negative effect of Ae. japonicus density on Ae. albopictus
      survival, but this effect was absent in the presence of malathion. There was also
      a moderate negative effect of Ae. japonicus density on Ae. albopictus female
      size, but this effect was absent in the presence of malathion. These findings
      indicate that pesticide-mediated alterations in competition and species-specific
      differences in susceptibility to pesticides could play a role in enhancing
      invasive potential of Ae. albopictus.

PMID- 21175049
TI  - Highly variable acquisition rates of Ixodes scapularis (Acari: Ixodidae) by birds
      on an Atlantic barrier island.
AB  - Acquisition of ticks by bird hosts is a central process in the transmission
      cycles of many tick-borne zoonoses, but tick recruitment by birds has received
      little direct study. We documented acquisition of Ixodes scapularis Say on birds
      at Fire Island, NY, by removing ticks from mist-netted birds, and recording the
      number of ticks on birds recaptured within 4 d of release. Eight bird species
      acquired at least 0.8 ticks bird(-1) day(-1) during the seasonal peak for at
      least one age class of I. scapularis. Gray Catbirds, Eastern Towhees, Common
      Yellowthroats, and Northern Waterthrushes collectively accounted for 83% of all
      tick acquisitions; and six individuals apportioned among Black-billed Cuckoo,
      Gray Catbird, Eastern Towhee, and Common Yellowthroat were simultaneously
      infested with both larvae and nymphs. Bird species with the highest acquisition
      rates were generally ground foragers, whereas birds that did not acquire ticks in
      our samples generally foraged above the ground. Tick acquisition by birds did not
      differ between deciduous and coniferous forests. Among the 15 bird species with
      the highest recruitment rates, acquisition of nymphs was not correlated with
      acquisition of larvae. Tick acquisition rates by individual bird species were not
      correlated with the reservoir competence of those species for Lyme borreliae.
      However, birds with high tick acquisition rates can contribute large numbers of
      infected ticks, and thus help maintain the enzootic cycle, even if their levels
      of reservoir competence are relatively low.

PMID- 21175051
TI  - Phenotypic variability of Rhodnius ecuadoriensis populations at the Ecuadorian
      central and southern Andean region.
AB  - Rhodnius ecuadoriensis is an important vector of Chagas disease in Ecuador.
      Whereas only sylvatic and peridomestic populations are common in Manabi province,
      this species occupies domestic, peridomestic, and sylvatic habitats in Loja
      province where high reinfestation of houses was observed. To explore the
      existence of phenetic changes linked to the domiciliation of the species, this
      study set out to analyze the wing and antennal phenotypes of R. ecuadoriensis in
      these two provinces where the vector presents different affinity for domestic
      habitats. The antennal phenotype and the wing size and shape distinguish the two
      geographical populations of R. ecuadoriensis. In Manabi, sylvatic and
      peridomestic specimens were very similar. In Loja, sylvatic and nonsylvatic
      (domestic and peridomestic) populations showed distinctive characteristics.
      Remarkable sexual dimorphism of wing and antenna, exclusive of domestic
      specimens, and high metric disparity in the wing shape of the domestic females
      point out the existence of a particular situation in this habitat. The results of
      this phenotypic analysis and previous evidence of behavioral differences support
      the hypothesis of disruptive selection acting upon R. ecuadoriensis populations.

PMID- 21175050
TI  - Development of microsatellites for genetic analyses and population assignment of
      the cat flea (Siphonaptera: Pulicidae).
AB  - Cat fleas, Ctenocephalidesfelis (Bouche) (Siphonaptera: Pulicidae), are common
      ectoparasites of companion animals that negatively impact their hosts directly by
      causing dermatitis and blood loss during feeding and indirectly through the
      potential transmission of disease causing agents. We isolated and characterized
      seven novel microsatellite loci from a partial genomic library of the cat flea
      enriched for di-, tri-, and tetranucleotide repeats. We screened these loci in
      cat fleas from two laboratory colonies and one wild-caught population collected
      at a temporary animal shelter (Parker coliseum) in Baton Rouge, LA. Six loci were
      polymorphic, with two to 15 alleles per locus and an average observed
      heterozygosity of 0.21 across populations. Although the two laboratory cat flea
      colonies were isolated from each other for many years, they did not significantly
      differ in their genotypic composition. The cat flea population from Parker
      coliseum was genetically different from the laboratory colonies, but also showed
      high degrees of inbreeding. Multilocus genotypes of the polymorphic loci were
      sufficient to assign over 85% of cat fleas to their population of origin. Genetic
      markers for flea population identity will allow further studies to examine the
      origins and movement of cat fleas with important genetic traits such as
      insecticide resistance or pathogen susceptibility. The use of microsatellites
      also could determine if there are host-specific strains of cat fleas and add
      insight into the development of the different subspecies of C. felis.

PMID- 21175052
TI  - Investigation of environmental influences on a transcriptional assay for the
      prediction of age of Aedes aegypti (Diptera: Culicidae) mosquitoes.
AB  - We examined the effects of environmental regulation of gene transcription on the
      accuracy of a transcriptional profiling method for determining insect age. In
      combined temperature/nutrition treatments, Aedes aegypti (L.) mosquitoes were
      maintained in the laboratory at three different temperatures (20, 26, and 32
      degrees C), and larvae were fed on low, medium, and high diet regimens. Adult
      mosquitoes of distinct size classes were produced. Transcription of three age
      responsive genes (Ae-15848, Ae-8505, and Ae-4274) was measured from 1-, 10-, and
      19-d-old specimens using a quantitative reverse-transcription polymerase chain
      reaction method incorporating dual-labeled TaqMan probes. Temperature had a
      significant effect on transcript abundance for two of the model genes (Ae-15848
      and Ae-8505), and transcription of model genes was unaffected by the main effect
      of larval diet level; however, significant temperature by diet level interactions
      were observed. Total RNA yield from individual mosquitoes varied according to
      adult age and temperature, and when combined with wing length, provided a useful
      predictor variable in age prediction models. More accurate age predictions were
      achieved from models generated at the same temperature as test mosquitoes;
      however, whereas significant differences in mean predicted ages were observed
      between 1- and 10-d-old mosquitoes, differences between 10 and 19 d were
      nonsignificant. This study highlights the effect of environmental regulation on
      gene transcription age grading and the need to identify additional gene
      biomarkers of age to improve the classification of older mosquitoes.

PMID- 21175053
TI  - Identification and expression profile of multiple genes in response to magnesium
      exposure in Culex quinquefasciatus larvae.
AB  - Magnesium is crucial for baculovirus transmission in Culex nigripalpus (Theobald)
      and Culex quinquefasciatus (Say) larvae. However, the mechanistic role of
      magnesium in baculovirus transmission is unknown. To investigate the possible
      role of host response factors in baculovirus transmission, suppression
      subtractive hybridization was used to identify genes differentially transcribed
      after magnesium exposure in Cx. quinquefasciatus larvae. Suppression subtractive
      hybridization was performed in both directions enriching for cDNAs differentially
      transcribed between a nonmagnesium larval control and magnesium (15 mM MgSO4)
      treatment of Cx. quinquefasciatus larvae held for 1 h at 27 degrees C. Clones
      from differentially transcribed genes were evaluated by sequencing, and relative
      gene transcription levels were analyzed using quantitative real-time polymerase
      chain reaction quantitative real-time polymerase chain reaction. Target
      transcripts up/downregulated by magnesium included Cx. quinquefasciatus troponin
      C, isocitrate dehydrogenase, allergen, cytochrome b5, chymotrypsinogen,
      apolipophorins, tryptase gamma, carboxylesterase, prolylcarboxypeptidase,
      imaginal disc growth factor, aldehyde dehydrogenase, tropomyosin-1,
      chitotriosidase, heat shock protein 70 B2, inorganic phosphate cotransporter, and
      many other hypothetical protein genes. Magnesium can alter gene transcription in
      a vector mosquito population, and understanding this process can provide insight
      into the mechanistic role of magnesium in baculovirus transmission.

PMID- 21175054
TI  - The influence of environmental temperature and humidity on temporal decomposition
      of cockroach allergens Bla g 1 and Bla g 2 in feces.
AB  - The aim of the study was to establish a model of the environmental fate of German
      cockroach (Blattella germanica L.) allergens Bla g 1 and Bla g 2 in feces under
      controlled and field conditions. Temporal decline (3, 6, and 9 mo) of allergens
      Bla g 1 and Bla g 2 in the feces protected from cleaning was measured under
      laboratory and experimental household conditions. The influence of environmental
      temperature (15, 20, 25, 30, and 35 degrees C) and moisture (53, 75, 85, and 100%
      RH) on allergen degradation was estimated for 3, 6, and 9 mo. Bla g 1 was more
      stable than Bla g 2 and the proteins. The proteins and Bla g 2 contents were
      correlated negatively with the decomposition time; Bla g 1 was not. However, when
      the content of Bla g 1 in control and exposed tubes was compared, the decrease
      after exposure was significant at exposure in 35 degrees C, 53 and 100% RH. In
      laboratory, the shortest half-life (16-38 d) of Bla g 2 was at high temperature
      and humidity (100% RH at 35 degrees C), whereas the longest half-life (340 d) was
      at 25 degrees C and 85% RH. In the apartment, the half-life was 406 d. The
      results indicate that Bla g 1 and Bla g 2 allergens can persist in feces for
      several months under usual household humidity and temperature.

PMID- 21175055
TI  - Cold storage of Culex pipiens in the absence of diapause.
AB  - A major expenditure in vector biology laboratories is the rearing of mosquitoes.
      Most mosquito colonies require substantial effort to maintain, including frequent
      bloodmeals for optimal performance. Successful cryopreservation of mosquitoes
      continues to be elusive. Although using diapause as a storage mechanism is an
      option for mosquito preservation, several obstacles include the lack of a well
      characterized diapause or the inability of some species to enter diapause. Thus,
      other options for preservation are needed. To address this issue, we investigated
      the use of long-term low-temperature storage in the absence of diapause for
      adults of the northern house mosquito, Culex pipiens L. Our results indicate that
      although male longevity is not substantially increased by cold storage, female
      longevity is dramatically increased by storage at lower temperatures. When mated
      before storage, females remain reproductively viable after at least 10 wk of
      storage, although at reduced levels. These results indicate that cold storage
      without diapause induction is a viable option for colony maintenance in vector
      biology laboratories.

PMID- 21175056
TI  - New findings of insecticide resistance in Triatoma infestans (Heteroptera:
      Reduviidae) from the Gran Chaco.
AB  - Chagas disease is a major health concern in Latin America, and Triatoma infestans
      (Klug, 1834) is responsible for the majority of cases of Chagas disease in the
      continent. After the discovery of deltamethrin highly resistant populations in
      the neighboring areas to Yacuiba (Bolivia) and Salvador Mazza (Argentina), we
      studied T. infestans populations north and southward, with the aim of describing
      the range of the resistant area. In addition, tests were conducted to describe
      the susceptibility to fipronil in deltamethrin-resistant populations. Tarija
      populations were highly resistant to deltamethrin, showing that the resistant
      area is greater than previously reported. Argentinean and Paraguayan populations
      were susceptible or presented moderate to low levels of deltamethrin resistance.
      Resistance to fipronil was found in Bolivian populations, although this
      insecticide was effective against Argentinean populations. This study shows that
      the Argentinean and Paraguayan populations are currently under successful control
      with deltamethrin. However, continuous resistance monitoring is necessary. We
      found that fipronil is a viable option for Argentina, whereas the resistance
      found in Bolivia implies that new formulations are needed to control T. infestans
      in Bolivia. Further research is required to find new alternatives of control in
      those areas that are currently suffering from high infestation rates.

PMID- 21175057
TI  - Dispersal and survival of Aedes albopictus (Diptera: Culicidae) males in Italian
      urban areas and significance for sterile insect technique application.
AB  - The dispersal and survival of laboratory-reared Aedes albopictus Skuse males were
      investigated during the summer of 2007 in three Northern Italy urban localities
      by mark-release-recapture techniques. Two marking methods were compared: one
      group of males was dusted with fluorescent pigments on the body (FP), and the
      other group was obtained from a strain whose natural infection of Wolbachia had
      been removed (WB0). FP- and WB0-marked males were released as adults and pupae,
      respectively, in one fixed station at each locality. Recaptures were performed by
      skilled technicians, within a radius of 350 m from the release site, on days 4,
      5, and 7 after the release, and the males were collected while flying around the
      technician's body or in swarms. Recapture rates ranged from 0.63 to 4.72% for FP
      males and from 2.39 to 11.05% for WB0 males. The mean distance traveled for WB0
      males was significantly higher than for FP males; no difference was observed
      between the dispersal distance measured for the males recaptured on human host
      versus males recaptured while swarming. No further increase of the dispersal
      occurred during the postrelease period investigated (from day 4 to day 7 after
      release). The mean survival rate at the release was 0.51 for FP-marked males and
      0.81 for WB0 males. The data obtained are discussed for their significance in
      planning sterile insect technique programs against Ae. albopictus.

PMID- 21175058
TI  - Irritant and repellent behavioral responses of Aedes aegypti male populations
      developed for RIDL disease control strategies.
AB  - Behavioral responses of Aedes aegypti male populations developed for Release of
      Insects Carrying a Dominant Lethal (RIDL) technology and a Malaysian wild-type
      population of two age groups (4-5 and 8-10 d old) were tested under laboratory
      conditions against chemical irritants and repellents using the high-throughput
      screening system device. Results indicate that all male Ae. aegypti test
      populations showed significant (P < 0.01) behavioral escape responses when
      exposed to alphacypermethrin, DDT, and deltamethrin at the test dose of 25
      nmol/cm2. In addition, all populations showed significant (P < 0.05) spatial
      repellent responses to DDT, whereas alphacypermethrin and deltamethrin elicited
      no directional movement in the assay. These data suggest that genetic
      modification has not suppressed expected irritancy and repellency behavior. Age
      effects were minimal in both contact irritant and spatial repellent assays. The
      magnitude of irritant response, based on percentage responding, was stronger in
      the RIDL test cohorts as compared with the wild-type Malaysian population, but
      the impact, if any, that this increased behavioral sensitivity might have on the
      success of a RIDL strategy has yet to be defined. Information of the type
      reported in the current study is vital in defining the effects of genetic
      modification on vector behavior and understanding how these behaviors may
      influence the success of RIDL technology as they relate to other vector control
      interventions implemented in the same disease-endemic locale.

PMID- 21175059
TI  - Prallethrin-induced excitation increases contact between sprayed ultralow volume
      droplets and flying mosquitoes (Diptera: Culicidae) in a wind tunnel.
AB  - Female Culex quinquefasciatus Say (Diptera: Culicidae) mosquitoes were exposed to
      sublethal amounts of prallethrin, sumithrin, and piperonyl butoxide applied as
      ultralow volume (ULV) droplets in a wind tunnel. Mosquitoes were video recorded
      before, during, and after treatment, and the number and size of droplets on their
      bodies were later determined using a compound microscope. A positive correlation
      was found between mosquitoes that spent more time flying during the time of
      spraying and number of droplets on their bodies. Excitation, in the form of
      increased speed and duration of flight, was immediate in mosquitoes exposed to
      prallethrin, whereas exposure to sumithrin did not increase their exposure to the
      ULV droplets. The location of droplets on mosquitoes, the effects of droplet
      volume, and subsequent mortality are discussed.

PMID- 21175060
TI  - Field applications of entomopathogenic fungi Beauveria bassiana and Metarhizium
      anisopliae F52 (Hypocreales: Clavicipitaceae) for the control of Ixodes
      scapularis (Acari: Ixodidae).
AB  - Two commercial formulations of Beauveria bassiana (Balsamo-Crivelli) Vuillemin
      were applied to residential sites in Old Lyme, CT, for the control of nymphs of
      the blacklegged tick, Ixodes scapularis, in 1999 and 2000. The pyrethroid
      bifenthrin was applied to other premises for comparison with B. bassiana. A wood
      chip barrier was installed and maintained at six of the treated properties. In
      1999, control of I. scapularis nymphs ranged from 74.5 to 83.0% on lawns without
      wood chips and from 88.9 to 90% on lawns with wood chip barriers. As a control
      check, no ticks (n = 23) collected at pretreatment or control sites died from B.
      bassiana, although 15 of 18 nymphs from treated lawns developed mycoses. Control
      of I. scapularis on the lawns in 2000 with the two B. bassiana products was
      lower, as follows: 38.0 and 58.7% without the barrier and 56.9 and 55.1% with the
      wood chip barrier. Posttreatment differences in nymphal numbers between
      treatments and control were significant (P = 0.005 and P = 0.039, 1999 and 2000,
      respectively). The bifenthrin provided 86 and 87% control each year,
      respectively. The application of Metarhizium anisopliae (Metschnikoff) Sorokin
      strain F52 to 9 residential sites in Westport and Weston, CT, in 2002 provided
      significant (P = 0.034; P = 0.039) reductions in nymphal tick abundance with 55.6
      and 84.6% fewer ticks on lawn and woodland plots, respectively. These results
      suggest the application of entomopathogenic fungi could provide another approach
      for the control of I. scapularis nymphs in residential or similar landscapes.

PMID- 21175061
TI  - A novel test cage with an air ventilation system as an alternative to
      conventional cages for the efficacy testing of mosquito repellents.
AB  - We have developed a novel test cage and improved method for the evaluation of
      mosquito repellents. The method is compatible with the United States
      Environmental Protection Agency, 2000 draft OPPTS 810.3700 Product Performance
      Test Guidelines for Testing of Insect Repellents. The Biogents cages (BG-cages)
      require fewer test mosquitoes than conventional cages and are more comfortable
      for the human volunteers. The novel cage allows a section of treated forearm from
      a volunteer to be exposed to mosquito probing through a window. This design
      minimizes residual contamination of cage surfaces with repellent. In addition, an
      air ventilation system supplies conditioned air to the cages after each single
      test, to flush out and prevent any accumulation of test substances. During biting
      activity tests, the untreated skin surface does not receive bites because of a
      screen placed 150 mm above the skin. Compared with the OPPTS 810.3700 method, the
      BG-cage is smaller (27 liters, compared with 56 liters) and contains 30 rather
      than hundreds of blood-hungry female mosquitoes. We compared the performance of a
      proprietary repellent formulation containing 20% KBR3023 with four volunteers on
      Aedes aegypti (L.) (Diptera: Culicidae) in BG- and conventional cages. Repellent
      protection time was shorter in tests conducted with conventional cages. The
      average 95% protection time was 4.5 +/- 0.4 h in conventional cages and 7.5 +/-
      0.6 h in the novel BG-cages. The protection times measured in BG-cages were more
      similar to the protection times determined with these repellents in field tests.

PMID- 21175062
TI  - Mode of action for natural products isolated from essential oils of two trees is
      different from available mosquito adulticides.
AB  - Insecticidal properties of natural products may present alternatives to the use
      of synthetic molecule pesticides that are of diminishing effectiveness due to
      resistance. Three compounds, thymoquinone, nootkatone, and carvacrol, components
      of Alaska yellow cedar, Chamaecyyparis nootkatensis (D. Don) Spach, and incense
      cedar, Calocedrus decurrens (Torr.), essential oils, have been shown to have
      biological activity against a variety of mosquito and tick species. Although
      these components act as both repellents and insecticides, how they function in
      either capacity is unknown. Their use as mosquito control insecticides would be
      greatly increased if their mode of action is not the same as that of currently
      used commercial products. This study compared the lethal dosages for nootkatone,
      carvacrol, and thymoquinone by using colony strains of Anopheles gambiae Giles
      with known mutations at three different target sites. The altered target sites
      evaluated were the sodium channel para-locus mutation (L1014 F KDR) that confers
      permethrin resistance, the ACE-1 gene that confers organophosphate and carbamate
      resistance, and a gamma-aminobutyric acid receptor mutation of the Rdl locus
      conferring dieldrin resistance. Significant increases in lethal dose were not
      observed in any of the mosquito strains for any of the compounds tested compared
      with the doses required of chemicals with known modes of action at the mutated
      sites. Although the mode of action was not determined, this screening study
      indicates that none of these compounds interact at the target sites represented
      in the test mosquito strains. These compounds represent a different mode of
      action than existing chemicals currently used in mosquito control.

PMID- 21175063
TI  - Inheritance of permethrin resistance in Culex quinquefasciatus.
AB  - The toxicity of permethrin to different life stages of Culex quinquefasciatus
      (Say) was examined in three field insecticide resistant strains, HAmCq(G0),
      MAmCq(G0), and BAmCq(G0); two permethrin selected strains, HAmCq(G8) and
      MAmCq(G6); and a laboratory susceptible strain, S-Lab. The levels of tolerance to
      permethrin differed among the developmental stages of Culex mosquito larvae with
      an ascending order from first to fourth instar. A developmentally regulated
      pattern of permethrin resistance in Culex mosquito larvae was identified, once
      again increasing from first to fourth instar. Adult mosquitoes had relatively
      lower levels of resistance in general compared with their larval stages,
      suggesting that different mechanisms may be involved in the response to
      insecticide selection pressure between larvae and adults. Inheritance of
      resistance to permethrin was examined using reciprocal crosses between resistant
      HAmCq(G8) and susceptible S-Lab strains; the resulting logarithm concentration
      probit response curves for reciprocal F1 lines were similar to those for the
      susceptible strain, with degree of dominance values of -0.2 to -0.3, suggesting
      that the inheritance of permethrin resistance in Cx. quinquefasciatus is
      incompletely recessive. No significant difference was found in the values of LC50
      and the slope of the log concentration-probit lines between reciprocal F1 lines,
      indicating that the resistance to permethrin was inherited autosomally. Both chi2
      goodness-of-fit test and log concentration-probit line analysis on responses of
      backcross and self-bred progeny to permethrin indicated that permethrin
      resistance in the HAmCq(G8) strain did not follow a monogenic gene inheritance
      model, revealing that permethrin resistance in Cx. quinquefasciatus is controlled
      by more than one gene.

PMID- 21175065
TI  - Purification and characterization of an antimicrobial peptide, insect defensin,
      from immunized house fly (Diptera: Muscidae).
AB  - The house fly, Musca domestica L. (Diptera: Muscidae), is involved in phoretic
      movement of pathogenic agents, but it has a very efficient defense mechanism
      against infection. It is believed that antimicrobial peptides play a significant
      role in the defense system of the house fly. Here, we isolated a peptide from the
      immunized house fly pupae, measured its molecular mass (3987.6 Da) by matrix
      assisted laser desorption ionization/time of flight-mass spectrometry, and
      determined its amino acid sequence by using the Procise Protein Sequencing System
      (Applied Biosystems, Foster City, CA). The peptide was confirmed as a member of
      the insect defensin family. It displayed high activity against gram-positive
      bacteria but lower activity against gram-negative bacteria and fungi. Reverse
      transcription-polymerase chain reaction showed that the house fly defensin gene
      was constitutively expressed in naive pupae and strongly up-regulated after
      immunization. House fly defensin is an amphiphilic peptide with a structure
      similar to that of the CSalphabeta scaffold of insect defensin A from the flesh
      fly, Phormia terraenovae Robineau-Desvoidy. To our knowledge, this is the first
      isolated and characterized house fly antimicrobial peptide, and our work may
      provide useful information for developing pharmacologically active antimicrobial
      agents.

PMID- 21175064
TI  - The effects of cypermethrin pour-on and piperonyl butoxide on Triatoma infestans
      under laboratory conditions.
AB  - The effect of exposing Triatoma infestans to chickens treated with cypermethrin
      pour-on combined with piperonyl butoxide (PBO) was studied. Four groups of
      treated chickens and one control group were used. Each treatment received 1 or 2
      ml of the cypermethrin formulation with and without PBO. Independent groups of
      nymphs were fed 1, 7, 15, 30, and 45 d after the treatment application. Blood
      intake was estimated after each feeding occasion. Up to 15 d after the pour-on
      application, high mortality was observed in all nymphs fed on treated chickens (>
      93% +/- 12), and lower than the nymphs of the control group (< 33% +/- 15). After
      30 d of the pour-on application, there was significantly different mortality
      between the treatment with 1 ml (80% +/- 9) and 2 ml (> 96% +/- 5); no difference
      was observed between groups with or without PBO addition. After 45 d of the pour
      on application, the treatments did not show significant differences (77% +/- 7),
      although all treatments showed higher mortality than the control group (10% +/-
      9). Up to 45 d after the pour-on application, blood intake by nymphs exposed to
      treated chickens (0.85 +/- 0.96 mg/nymph) was lower than blood intake by nymphs
      exposed to control chickens (6.7 +/- 5 mg/nymph). This study shows that
      cypermethrin pour-on produces high mortality and reduces the blood intake of
      third-instar nymphs of T. infestans up to 45 d after the insecticide application
      to chickens. PBO did not produce a detectable effect.

PMID- 21175066
TI  - Differential expression of salivary gland genes in the female sand fly
      Phlebotomus papatasi (Diptera: Psychodidae).
AB  - Saliva from blood-sucking arthropods modulates host homostasis and immunity,
      making salivary components potential candidates to be used against pathogens
      transmitted by these biting insects. Functional characterization of salivary
      molecules is fundamental to gain a better understanding into their roles during
      blood feeding and to determine under which conditions such molecules are
      expressed in the insect saliva. In the current study, we investigated the
      expression profile of 10 salivary genes from the sand fly Phlebotomus papatasi
      (Scopoli) (Diptera: Psychodidae), a principal vector of Leishmania major. Our
      analyses using quantitative polymerase chain reaction were aimed at defining
      whether diet or senescence influences the expression of P. papatasi salivary
      gland-expressed genes in laboratory-reared female sand flies. Our results
      demonstrate that at least one of the most abundant salivary transcripts, SP44, is
      consistently modulated by either senescence or diet. In contrast, another
      abundant transcript, SP32, was expressed without any influence from the diet
      received or the age of the sand fly. Differential expression of the other eight
      transcripts was not consistently regulated by either diet or age, suggesting that
      other factors may have a greater influence on differential expression of these
      salivary gland proteins.

PMID- 21175067
TI  - Antibody response against Anopheles albimanus (Diptera: Culicidae) salivary
      protein as a measure of mosquito bite exposure in Haiti.
AB  - Antibodies against arthropod saliva have shown to be a good marker of bite
      exposure. Because Anopheles albimanus Wiedemann (Diptera: Culicidae) is the
      principal malaria vector in Haiti, we evaluated the immune response against
      salivary gland extract (SGE) of this species in malaria-positive and malaria
      negative subjects from this country. The results showed that the level of anti
      SGE immunoglobulin (Ig)G antibodies was higher in patients with clinical malaria
      than those in malaria uninfected people living in the same region. In addition, a
      significant positive correlation between the level of anti-An. albimanus IgG and
      IgM antibody levels was observed. These results suggest that antibodies against
      An. albimanus saliva, especially IgG, are useful markers of mosquito bite
      exposure in Haiti.

PMID- 21175068
TI  - Bloodmeal size and spirochete acquisition of Ornithodoros hermsi (Acari:
      Argasidae) during feeding.
AB  - Ornithodoros hermsi Wheeler (Acari: Argasidae) is the vector of Borrelia hermsii,
      the primary cause of tick-borne relapsing fever in North America. This tick is
      one of the smallest Ornithodoros species involved with the biological
      transmission of spirochetes; yet, the amount of blood ingested while feeding is
      unknown. Therefore, we determined the amount of blood O. hermsi ingested during a
      bloodmeal to establish its potential for spirochete acquisition while feeding on
      an infected host. Ticks at different developmental stages were weighed before and
      after feeding and the volume of blood ingested was calculated. Females ingested
      the most blood, averaging approximately 15 microl per meal, but late-stage nymphs
      took in the most blood in proportion to unfed body weight. A cohort of nymphs was
      weighed three more times during the 48 h after feeding, which demonstrated that
      O. hermsi may have excreted coxal fluid ranging from 24 - 36% of the bloodmeal
      weight. We also developed a quantitative polymerase chain reaction method to
      determine the number of spirochetes ingested and maintained within the ticks
      after feeding. The density of spirochetes in ticks having just engorged was
      slightly less than in the host's blood. In the first 5 d after feeding, the
      number of spirochetes within the ticks declined from the number initially
      ingested but then remained constant through 15 d. These observations establish a
      basis for future studies to determine the minimum number of spirochetes required
      in the host's blood to allow O. hermsi to become persistently infected and
      transmit during subsequent bloodmeals.

PMID- 21175069
TI  - Rickettsial infections of fleas collected from small mammals on four islands in
      Indonesia.
AB  - Ectoparasites were sampled from small mammals collected in West Java, West
      Sumatra, North Sulawesi, and East Kalimantan, Indonesia, in 2007-2008 and were
      screened for evidence of infection from bacteria in the Rickettsaceae family.
      During eight trap nights at eight sites, 208 fleas were collected from 96 of 507
      small mammals trapped from four orders (379 Rodentia; 123 Soricomorpha; two
      Carnivora; three Scandentia). Two species of fleas were collected: Xenopsylla
      cheopis (n = 204) and Nosopsyllus spp. (n = 4). Among the 208 fleas collected,
      171 X. cheopis were removed from rats (Rattus spp.) and 33 X. cheopis from shrews
      (Suncus murinus). X. cheopis were pooled and tested for DNA from rickettsial
      agents Rickettsia typhi, Rickettsia felis, and spotted fever group rickettsiae.
      R. typhi, the agent of murine typhus, was detected in X. cheopis collected from
      small mammals in West Java and East Kalimantan. R. felis was detected in X.
      cheopis collected from small mammals in Manado, North Sulawesi. R. felis and
      spotted fever group rickettsiae were detected in a pool of X. cheopis collected
      from an animal in East Kalimantan. Sixteen percent of the X. cheopis pools were
      found positive for Rickettsia spp.; four (10.8%) R. typhi, one (2.7%) R. felis,
      and one (2.7%) codetection of R. felis and a spotted fever group rickettsia.
      These data suggest that rickettsial infections remain a threat to human health
      across Indonesia.

PMID- 21175070
TI  - Efficacy of commercial mosquito traps in capturing phlebotomine sand flies
      (Diptera: Psychodidae) in Egypt.
AB  - Four types of commercial mosquito control traps, the Mosquito Magnet Pro (MMP),
      the Sentinel 360 (S360), the BG-Sentinel (BGS), and the Mega-Catch Ultra (MCU),
      were compared with a standard Centers for Disease Control and Prevention (CDC)
      light trap for efficacy in collecting phlebotomine sand flies (Diptera:
      Psychodidae) in a small farming village in the Nile River Valley 10 km north of
      Aswan, Egypt. Each trap was baited with either carbon dioxide (CO2) from
      combustion of butane gas (MMP), dry ice (CDC and BGS traps), light (MCU and
      S360), or dry ice and light (CDC). Traps were rotated through five sites in a5 x
      5 Latin square design, repeated four times during the height of the sand fly
      season (June, August, and September 2007) at a site where 94% of sand flies in
      past collections were Phlebotomus papatasi (Scopoli). A total of 6,440 sand flies
      was collected, of which 6,037 (93.7%) were P. papatasi. Of the CO2-baited traps,
      the BGS trap collected twice as many P. papatasi as the MMP and CDC light traps,
      and at least three times more P. papatasi than the light-only MCU and S360 traps
      (P < 0.05). Mean numbers (+/- SE) of P. papatasi captured per trap night were as
      follows: BGS 142.1 (+/- 45.8) > MMP 56.8 (+/- 9.0) > CDC 52.3 (+/- 6.1) > MCU
      38.2 (+/- 6.4) > S360 12.6 (+/- 1.8). Results indicate that several types of
      commercial traps are suitable substitutes for the CDC light trap in sand fly
      surveillance programs.

PMID- 21175071
TI  - Mosquito vectors of West Nile virus during an epizootic outbreak in Puerto Rico.
AB  - The purpose of this investigation was to identify the mosquito (Diptera:
      Culicidae) vectors of West Nile virus (WNV; family Flaviviridae, genus
      Flavivirus) during an epizootic WNV outbreak in eastern Puerto Rico in 2007. In
      June 2006, 12 sentinel chicken pens with five chickens per pen were deployed in
      six types of habitats: herbaceous wetlands, mangrove forests, deciduous forests,
      evergreen forests, rural areas, and urban areas. Once WNV seroconversion in
      chickens was detected in June 2007, we began trapping mosquitoes using Centers
      for Disease Control and Prevention (CDC) miniature (light/CO2-baited) traps, CMT
      20 collapsible mosquito (CO2- and ISCA SkinLure-baited) traps, and CDC gravid
      (hay infusion-baited) traps. We placed the CDC miniature traps both 2-4 m and >30
      m from the chicken pens, the collapsible traps 2-4 m from the pens, and the
      gravid traps in backyards of houses with sentinel chicken pens and in a wetland
      adjacent to an urban area. We found numerous blood-engorged mosquitoes in the
      traps nearest to the sentinel chickens and reasoned that any such mosquitoes with
      a disseminated WNV infection likely served as vectors for the transmission of WNV
      to the sentinels. We used reverse transcriptase-polymerase chain reaction and
      isolation (C636) on pools of heads, thoraxes/ abdomens, and legs of collected
      blood-engorged mosquitoes to determine whether the mosquitoes carried WNV. We
      detected WNV-disseminated infections in and obtained WNV isolates from Culex
      nigripalpus Theo (minimum infection rate [MIR] 1.1-9.7/1,000), Culex bahamensis
      Dyar and Knab (MIR 1.8-6.0/1,000), and Aedes taeniorhynchus (Wied.) (MIR 0.34
      0.36/1,000). WNV was also identified in and isolated from the pool of thoraxes
      and abdomens of Culex quinquefasciatus Say (4.17/1,000) and identified in one
      pool of thoraxes and abdomens of Culex habilitator Dyar and Knab (13.39/1,000).
      Accumulated evidence since 2002 suggests that WNV has not become endemic in
      Puerto Rico.

PMID- 21175072
TI  - Survival of Ixodes ricinus (Acari: Ixodidae) under challenging conditions of
      temperature and humidity is influenced by Borrelia burgdorferi sensu lato
      infection.
AB  - ABSTRACT To determine whether Borrelia burgdorferi sensu lato (s.l.) influences
      tick survival under thermohygrometric stress, Ixodesricinus (L.) (Acari:
      Ixodidae) questing ticks were tested under various relative humidities (13, 32,
      51.5, 61, and 89% RH) at two different temperatures (12.5 and 25 degrees C) and
      investigated for Borrelia infection. Survival rate of females was highest
      (77.6%), followed by males (51.6%), and nymphs (43.2%). The thermohygrometric
      factor that most importantly determined survival was saturation deficit (SD). As
      SD increased, tick survival rate decreased in all stages. Among the 1,500 ticks
      tested for B. burgdorferi s.l., 34.8% (n = 522) were infected. Adult infection
      rate (39.6%) was higher than that of nymphs (25.5%). Infection load in real-time
      polymerase chain reaction ranged from 1 to 1.2 million spirochetes per tick. B.
      afzelii (39.7%), B. burgdorferi sensu stricto (12.1%), B. garinii (37.9%), B.
      myamotoi (3.6%), and B. valaisiana (23.8%) were recorded. B. garinii infected
      significantly less nymphs than adults whereas B. afzelii displayed the opposite
      trend. Survival rate of nymphal and adult I. ricinus was significantly enhanced
      by infection by B. burgdorferi s.l. (Chi(2): nymph, P = 0.008; adult, P = 0.021).
      In adults, a negative effect of infection on tick survival was observed when
      spirochete load overcame a threshold estimated at 160,000 spirochetes per tick
      but not in nymphs. Moreover, ticks infected by B. afzelii survived better than
      other ticks (infected by other genospecies or not). The results here indicate
      that infection by B. burgdorferi s.l., and more specifically infection by B.
      afzelii, confers survival advantages to I. ricinus under challenging
      thermohygrometric conditions.

PMID- 21175073
TI  - Detection of West Nile virus in stable flies (Diptera: Muscidae) parasitizing
      juvenile American white pelicans.
AB  - Stable flies, Stomoxys calcitrans (L.) (Diptera: Muscidae), an economically
      important pest of livestock and humans, were observed parasitizing prefledged
      American white pelicans, Pelecanus erythrorhynchos (Pelecaniformes: Pelecanidae),
      in a pelican breeding colony in northeastern Montana where die-offs attributed to
      West Nile virus (family Flaviviridae, genus Flavivirus, WNV) have occurred since
      2002. Engorged and unengorged flies were collected off nine moribund chicks. Of
      29 blood-engorged flies testing positive for vertebrate DNA, all 29 contained
      pelican DNA. Virus isolation was performed on 60 pools (1,176 flies) of
      unengorged flies using Vero cell plaque assay. Eighteen pools were positive for
      WNV for an estimated infection rate of 18.0 per 1,000 flies. Fifty-four percent
      (36/67) of abdomens from blood-engorged flies tested positive for WNV. Pelican
      viremia levels from the blood-engorged fly abdomens revealed that at least one of
      the ill pelicans circulated a viremia capable of infecting Culex mosquito
      vectors. Stable flies may be involved in WNV transmission within the pelican
      breeding colony by serving as either a mechanical vector or as a source for oral
      infection if ingested by predators.

PMID- 21175074
TI  - Phlebotomine sand flies (Diptera: Psychodidae) and Leishmania infection in
      Gafanhoto Park, Divinopolis, Brazil.
AB  - The potential of Gafanhoto Park as an American cutaneous leishmaniasis (ACL)
      focus was evaluated by examination of sand fly vectors of the Leishmania
      parasite. This forest remnant is located in a periurban area of Divin6polis,
      Brazil, where autochthonous cases of ACL have been reported. Sand fly populations
      were monitored over a 2-yr period (2006-2008) by using light traps (HP and
      Shannon). During systematic collections with HP traps, 824 specimens in total
      (342 males and 482 females) of 21 species were captured. Most prevalent species
      were as follows: Brumptomyia brumpti (Larrouse), Lutzomyia aragaoi (Costa Lima),
      Lutzomyia lutziana (Costa Lima), Lutzomyia sordellii (Shannon & Del Ponte), and
      Lutzomyia whitmani (Antunes & Coutinho). Using Shannon traps, 257 specimens
      representing 15 species were collected (159 females and 98 males), with a high
      prevalence of L. whitmani and Lutzomyia neivai (Pinto), both vectors of
      Leishmania braziliensis (Vianna). To ascertain the level of natural infection, a
      sample of females captured in Shannon traps was assayed for the presence of
      Leishmania by using polymerase chain reaction-restriction fragment length
      polymorphism, where 39% of insects were positive. The most infected species was
      L. whitmani (29 sand flies; 18.2%), followed by L. neivai (21; 13.2%), Lutzomyia
      christenseni (Young & Duncan) (five; 3.1%), Lutzomyia pessoai (Coutinho &
      Barreto) (three; 1.9%), L. aragaoi (one; 0.6%), Lutzomyia fischeri (Pinto) (one;
      0.6%), Lutzomyia lenti (Mangabeira) (one; 0.6%), L. lutziana (one; 0.6%), and
      Lutzomyia monticula (Costa Lima) (one; 0.6%). The finding of potential and
      incriminated vectors naturally infected with Leishmania reinforces the need of
      epidemiologic surveillance in the area.

PMID- 21175075
TI  - Expression profile of prophenoloxidase-encoding (acppo6) gene of Plasmodium vivax
      refractory strain of Anopheles culicifacies.
AB  - Anopheles culicifacies is the main vector for transmission of Plasmodium vivax
      malaria in the Indian subcontinent. A strain of An. culicifacies isolated from
      its natural niche displayed complete refractoriness to P. vivax by melanotic
      encapsulation of ookinetes. Prophenoloxidases are key components of the
      phenoloxidase cascade that leads to recognition and melanization of invading
      organisms. We isolated and cloned prophenoloxidase-encoding acppo6 gene of An.
      culicifacies and analyzed its expression profile under various regimens of immune
      challenge. The acppo6 was differentially expressed during various stages of
      larval development. The acppo6 transcription was also up-regulated in response to
      bacteria and Plasmodium vinckei petteri challenge. The transcript levels of the
      acppo6 gene were higher in naive adult refractory female mosquitoes as compared
      with female susceptible mosquitoes. Furthermore, the induction of acppo6 in the
      susceptible strain upon Plasmodium infection was negligible as compared with that
      of the refractory strain. The observation is suggestive of the role of acppo6 in
      effectuating a melanotic response in Plasmodium-incompetent naturally occurring
      refractory An. culicifacies strain.

PMID- 21175076
TI  - New record of Lipoptena cervi and updated checklist of the louse flies (Diptera:
      Hippoboscidae) of the Republic of Korea.
AB  - ABSTRACT This is the first confirmed record of the genus Lipoptena Nitzsch and
      its species, Lipoptena cervi (Linnaeus), from the Republic of Korea. A total of
      five females and 10 males was collected from eight of 29 Korean water deer,
      Hydropotes inermis argyropus Swinhoe, from Gangwon and Gyeongsangbuk Provinces
      and Ulsan Metropolitan Area from May through October 2008. An updated checklist
      of Korean hippoboscids contains nine species in six genera (Hippobosca Linnaeus,
      Icosta Speiser, Lipoptena, Ornithoctona Speiser, Ornithomya Lattreille, and
      Ornithophila Rondani). Hosts, collection records, and repositories are also
      noted.

PMID- 21175077
TI  - Examination of a miniaturized funnel trap for Aedes aegypti (Diptera: Culicidae)
      larval sampling.
AB  - Funnel traps are often used to sample for the presence of Aedes aegypti (L.)
      (Diptera: Culicidae) larvae in subterranean aquatic habitats. These traps are
      generally > or = 15 cm in diameter, making them impractical for use in
      subterranean sites that have narrow (10-cm) access ports, such as those in
      standard-sized septic tanks. Recent research indicates septic tanks may be
      important habitats for Ae. aegypti in Puerto Rico and the Caribbean. To sample
      mosquito larval populations in these sites, a miniaturized funnel trap was
      necessary. This project describes the use of a smaller funnel trap for sampling
      larval populations. The effects of larval instar (third and fourth) and
      population density on trap efficacy also are examined. The trap detected larval
      presence 83% of the time at a larval density of 0.011 larvae per cm(2) and 100%
      of the time at densities > or = 0.022 larvae per cm(2). There was a significant
      trend of increasing percentage of recaptured larvae with higher larval population
      densities. Although the miniaturized funnel trap is less sensitive at detecting
      larval presence in low population densities, it may be useful for sampling
      aquatic environments with restricted access or shallow water, particularly in
      domestic septic tanks.

PMID- 21175078
TI  - Temperature affects emergence of Crataerina pallida (Diptera: Hippoboscidae).
AB  - Despite knowledge of parasite biology being essential for host-parasite system
      functioning to be understood, the life histories of many parasites remain little
      studied. One example being the hippoboscid Crataerina pallida (Olivier in
      Latreille, 1812) (Diptera: Hippoboscidae), a nest ectoparasite of the common
      swift, Apus apus L. (Aves: Apodidae). The factors influencing adult parasite
      emergence remain unclear. Whether temperature affects emergence was studied by
      exposing overwintering pupae to differing temperature regimes. At higher
      temperatures, greater numbers of adults emerged. This indicates that adult
      hatching is temperature mediated and may be enhanced by host presence. The
      relationship between C. pallida and their hosts is thus close.

PMID- 21175079
TI  - High-prevalence Borrelia miyamotoi infection among [corrected] wild turkeys
      (Meleagris gallopavo) in Tennessee.
AB  - During spring and fall 2009, 60 wild turkeys (Meleagris gallopavo) harvested by
      Tennessee hunters were surveyed for Borrelia spp. by sampling their blood,
      tissue, and attached ticks. In both seasons, 70% of turkeys were infested with
      juvenile Amblyomma americanum; one spring turkey hosted an adult female Ixodes
      brunneus. Polymerase chain reaction assays followed by DNA sequencing indicated
      that 58% of the turkeys were positive for the spirochete Borrelia miyamotoi, with
      tissue testing positive more frequently than blood (P = 0.015). Sequencing of the
      16S-23S rRNA intergenic spacer indicated > or = 99% similarity to previously
      published sequences of the North American strain of this spirochete. Positive
      turkeys were present in both seasons and from all seven middle Tennessee counties
      sampled. No ticks from the turkeys tested positive for any Borrelia spp. This is
      the first report of B. miyamotoi in birds; the transmission pathways and
      epidemiological significance of this high-prevalence spirochetal infection remain
      uncertain.

PMID- 21175080
TI  - Ticks infesting wildlife species in northeastern Brazil with new host and
      locality records.
AB  - From September 2008 to March 2010, 397 ticks (315 larvae, 33 nymphs, 23 females,
      and 26 males) were collected from captive and free-living wildlife species in
      northeastern Brazil. Six tick species were identified, including Amblyomma
      auricularium (Conil) on Tamandua tetradactyla (L.), Amblyomma dubitatum Neumann
      on Hydrochaeris hydrochaeris (L.), Nectomys rattus (Pelzen) and T. tetradactyla,
      Amblyomma parvum Aragao on T. tetradactyla, Amblyomma rotundatum Koch on Boa
      constrictor L., Chelonoidis carbonaria (Spix), Kinosternon scorpioides (L.) and
      Rhinella jimi (Stevaux), Amblyomma oarium Koch on Bradypus variegatus Schinz, and
      Rhipicephalus sanguineus (Latreille) on Lycalopex vetulus (Lund). Nectomys rattus
      and T. tetradactyla are new hosts for A. dubitatum. This study extends the known
      distribution ofA. dubitatum in South America and provides evidence that its
      geographical range has been underestimated because of the lack of research. Four
      (A. dubitatum, A. parvum, A. rotundatum, and R. sanguineus) of six tick species
      identified in this study have previously been found on humans in South America,
      some of them being potentially involved in the transmission of pathogens of
      zoonotic concern.

PMID- 21175081
TI  - The soy that surrounds us: an endless debate.

PMID- 21175082
TI  - Soy as an endocrine disruptor: cause for caution?
AB  - Endocrine disrupting compounds (EDCs) alter the function of the endocrine system
      and consequently cause adverse health effects. Phytoestrogens, natural plant
      compounds abundantly found in soy and soy products, behave as weak estrogen
      mimics or as antiestrogens. They are considered to be EDCs, and have some
      beneficial effects on health, including reducing the risk of breast cancer and
      improving metabolic parameters. However, the supporting evidence that consumption
      of phytoestrogens is beneficial is indirect and inconsistent. Lifetime exposure
      to estrogenic substances, especially during critical periods of development, has
      been associated with formation of malignancies and several anomalies of the
      reproductive systems. Phytoestrogen consumption in infants, through soy-based
      formulas, is of particular concern. Prospective epidemiological studies for the
      evaluation of the effect of phytoestrogens alone, and in combination with other
      estrogenic chemicals, are lacking, yet possible adverse effects should not be
      taken lightly.

PMID- 21175083
TI  - Mass ascites in Mulibrey nanism.

PMID- 21175084
TI  - Delayed gastric emptying in patients with Prader Willi Syndrome.
AB  - BACKGROUND: A 15 year old girl with Prader-Willi Syndrome (PWS) died of gastric
      rupture. Systematic literature research revealed seven case reports of PWS
      patients with acute gastric dilatation, two had a lethal course. The objective of
      this study was to determine if delayed gastric emptying in PWS patients might
      contribute to gastric dilatation. METHODS: Gastric emptying was measured in eight
      patients with PWS by nucleotid scintigraphy after a standardized test meal.
      RESULTS: Median age was 17.8 years (range 10.1-19.5). Median BMI of the male
      patients was 29.5 (range 18.4-34.8), of the female patients 28 (range 20.0-44.8).
      Half time of gastric emptying was delayed in five of the eight patients (median
      78.5 minutes, range 59-134). CONCLUSION: Scintigraphic measurement of gastric
      emptying in eight PWS patients revealed delay in comparison to normal values.
      This might be a risk factor for gastric dilatation and rupture in patients with
      PWS.

PMID- 21175085
TI  - Age and sex differences in fat distribution in non-obese Japanese children.
AB  - OBJECTIVE: To assess fat distribution in non-obese Japanese children and
      adolescents. DESIGN: 130 non-obese Japanese children (73 boys and 57 girls) from
      Kikugawa, Hamamatsu were included. The visceral fat area (VFA) and subcutaneous
      fat area (SFA) were measured by computed tomography (CT) and calculated (in
      cm(2)). Subjects were divided into three groups based on age: group A (6-10
      years), group B (11-15 years), and group C (16-20 years). RESULTS: Girls had more
      subcutaneous fat than boys in groups B and C (P<0.01). Boys had an age-dependent
      increase in visceral fat, but girls did not. In group C (16-20 years), boys had
      more visceral fat than girls (P<0.01). CONCLUSIONS: In non-obese Japanese
      children, there are significant differences in visceral and subcutaneous fat
      amounts by age and sex. VFA seems to accumulate more in boys than in girls, and
      SFA is more prevalent in girls than boys.

PMID- 21175086
TI  - Premature thelarche in Taiwanese girls.
AB  - This study was conducted to understand the clinical features and natural course
      of Taiwanese girls with premature thelarche (PT). The medical records of 91
      Taiwanese girls with PT who were diagnosed younger than six and have been
      regularly followed up for more than two years were reviewed. For comparison, GnRH
      test was also done in 25 girls with central precocious puberty (CPP) and 10
      normal prepubertal girls. The age of onset of these patients was 1.5 +/- 1.6
      years and 79% of them developed PT before the age of two. Girls with PT had
      intermediate degree of hypothalamic-pituitary-ovarian activity between prepuberty
      and CPP with FSH-predominant response to GnRH stimulation. 87% of patients have
      complete regression of breast development during 3.8 +/- 2.5 years' follow-up but
      19% of them have progressed to CPP during follow-up. We conclude that Taiwanese
      girls with PT more often developed within the first two years of life. Activation
      of hypothalamic-pituitary-gonadal axis with predominant FSH activity during
      infancy may contribute to its development. In addition, PT is not always a benign
      self-limited condition, and clinicians should be cautious about pubertal
      development of these patients.

PMID- 21175087
TI  - Growth hormone, insulin like growth factor-1, and insulin-like growth factor
      binding protein-3 levels in the neonatal period: a preliminary study.
AB  - BACKGROUND: Growth hormone (GH), insulinlike growth factor-1 (IGF-1), and IGF
      binding protein-3 (IGFBP-3) are used in the neonatal period for evaluation of
      diseases such as GH deficiency, intrauterine growth restriction, and
      hypoglycemia. However, GH level has been reported as a single value during the
      neonatal period. In this study, we attempted to determine the changes of GH, IGF
      1, and IGFBP-3 in the neonatal period for each week. METHODS: One hundred and two
      appropriate-for-gestational age (AGA) term neonates who did not have any diseases
      that would interfere with GH-IGF axis were included in this cross-sectional
      study. Blood samples were collected and serum GH, IGF-1 and IGFBP-3 levels were
      measured by immunoradiometric analysis (IRMA) and weekly values were obtained for
      the first postnatal four weeks. RESULTS: We showed that GH level [median (1st-3rd
      quartile)] decreases from the first to the fourth postnatal week [25.1 (18.5
      37.4); 17.2 (13.2-22.8); 17.6 (12.2-20.2); 14.4 (6.60-19.8) ng/mL,
      respectively)], IGF-1 and IGFBP-3 levels [median (lst-3rd quartile)] increase
      [41.7 (18.0-70.0); 55.9 (39.0-103); 53.0 (40.0-97.7); 71.7 (44.3-137) and 1852
      (1597-2451); 2430 (1645-2838); 2841 (2280-3675); 3018 (2151-4189) ng/mL,
      respectively)]. CONCLUSIONS: GH, IGF-1 and IGFBP-3 values can be evaluated for
      each week separately instead of for the entire neonatal period.

PMID- 21175088
TI  - Bone maturation in 1788 children and adolescents with diabetes mellitus type 1.
AB  - Diabetes mellitus type 1 might interfere with pubertal development. Particularly,
      long-term metabolic control and intensity of insulin treatment have been reported
      to contribute to a delay in pubertal onset. Data on somatic development in
      diabetic children are conflicting; therefore we studied bone age in 1788 children
      from Germany and Austria with type 1 diabetes. Bone age was retarded by -0.27 +/-
      1.1 years in the whole group, but particularly in the adolescents at the end of
      puberty (>16 years; -0.76 +/- 1.29y). Bone age delay was more pronounced in boys,
      and in children with long-term median HbAlc levels of 7.5 - 9.0%. No associations
      were found with current HbAlc levels or the intensity of insulin treatment. Bone
      age determinations in diabetic children should only be performed when clinical
      signs of impaired somatic development are present. In addition, the potential
      influence of diabetes on bone development needs to be considered in the
      interpretation of carpograms.

PMID- 21175089
TI  - Serum thyroid hormone levels in preterm infants born before 33 weeks of gestation
      and association of transient hypothyroxinemia with postnatal characteristics.
AB  - BACKGROUND: Fetal thyroid function and the hypothalamopituitary-thyroid axis
      continue to mature throughout pregnancy. Therefore, thyroid hormone levels of
      premature infants differ from those of mature ones. Our primary objective was to
      evaluate the reference values of serum thyroid hormones in preterm infants born
      before 33 wk gestation. The second objective was to define a cut-off value for
      transient hypothyroxinemia of prematurity (THOP) according to gestational age and
      association of THOP with postnatal characteristics in these infants. SUBJECTS AND
      METHODS: We recruited a cohort of 200 infants (26-32 wk gestation) admitted to
      neonatal intensive care units (NICU) between March 2008 and February 2009. We
      assessed serum levels of thyroid hormones and thyrotropin (TSH), at 1st, 2nd, and
      3rd-4th wk of life. Thyroid-binding globulin (TBG), thyroglobulin (Tg), and
      urinary iodine values were also measured at the 1st wk of life. The infants were
      divided into two groups according to gestational ages; group 1: 26-29 wk and
      group 2: 30-32 wk. Association of THOP with postnatal characteristics of these
      infants were evaluated. RESULTS: TT4 and TT3 values steadily increased from 1st
      wk to 3rd-4th wk while FT4 value did not significantly changed. FT3 value
      slightly decreased from 1st wk to 2nd wk and not significantly changed after this
      period. TSH value steadily decreased from 1st wk to 3rd-4th wk. For all postnatal
      ages, TT4, TT3, and FT3 values were lower in the lower gestational age group,
      while there was no significant difference for FT4 and TSH values between two
      gestational age groups. THOP rate decreased from first wk (24.0%, n=47) to 3rd
      4th (14.0%, n=24) in all infants. When adjusted for age, THOP was associated with
      need for mechanical ventilation (P=0.03, OR:0.65, CI 95% 0.4-0.9) and for having
      respiratory distress syndrome (RDS) (P=0.02, OR:0.61 CI95%: 0.4-0.9). Longer
      hospital stay (P=0.006, OR:0.96, CI 95% 0.94-0.99) was also found to be
      associated with THOP. CONCLUSIONS: In preterm infants below 30 wk, thyroid
      hormones were lower and urinary iodine values were higher compared to infants
      with older gestational age. THOP at the first wk of life may convey important
      prognostic information about neonatal morbidity and length of hospitalization
      stay.

PMID- 21175090
TI  - Birth length is a predictor of adiponectin levels in Japanese young children.
AB  - BACKGROUND: Adiponectin has been shown to be inversely related to birth weight in
      schoolchildren and adolescents. However, the available information regarding a
      relation between birth size and adiponectin in infants and preschoolers is
      limited. METHODS: A longitudinal study was conducted among healthy Japanese
      children, and serum adiponectin levels were measured at consecutive visits. The
      effect of sex, gestational age, birth length, birth weight, or placental weight
      on adiponectin was analyzed by using a linear mixed model for repeated measures.
      RESULTS: Eighty-three children were evaluated. The age range at the first visit
      was 0.07-5.3 years. A total number of 227 measurements were made, 1-12 per
      subject (median, 3) and the duration of follow-up ranged from 1 day to 2.3 years
      (median, 1.0 years). The subjects were divided into four groups according to the
      age at the first visit: (1) 0-2 months (n = 29), (2) 3 months to 1 year (n = 17),
      (3) 2-3 years (n = 19) and (4) 4-5 years (n = 18). In the multivariate model,
      birth length (coefficient = 3.94, 95% CI, 0.23-7.65) was an independent predictor
      of serum adiponectin levels in subjects aged 0-2 months. Gestational age (3.53,
      1.14-5.92), birth length (-2.71, -4.90 to -0.53) and placental weight (2.58, 0.86
      4.29) were independent predictors of serum adiponectin levels in subjects aged 4
      5 years. CONCLUSION: Birth length, not birth weight, is an independent predictor
      of serum adiponectin levels in Japanese young children.

PMID- 21175091
TI  - Genotype-phenotype correlation in CAH patients with severe CYP21A2 point
      mutations in the Republic of Macedonia.
AB  - Steroid 21-hydroxylase deficiency is a most frequent cause of congenital adrenal
      hyperplasia (CAH), due to mutations in the CYP21A2 gene. Approximately 75% of
      patients with classical form of CAH have severe impairment of 21-hydroxylase
      activity. METHODS: We have performed direct molecular diagnosis of the nine
      common CYP21A2 point mutations in 24 Macedonian CAH patients from 20 unrelated
      families, using differential PCR and ACRS. RESULTS: Five of the analysed
      mutations were detected in 23 patients: 15 patients were homozygous for one
      mutation, four patients were compound heterozygotes and four patients were
      heterozygotes. The most common was IVS2-13A/C mutation found in 60.4% of the
      alleles, followed by Q318X (22.9%), R356W (4.2%), V281L (2.1%) and P30L (2.1%).
      The concordance of genotype to phenotype in the patients was 83.3% with complete
      concordance in the genotypes predicting the SW and SV phenotype. CONCLUSION: The
      distribution of the detected mutations in the Macedonian CAH patients was similar
      with those described in other European populations. The genotype-phenotype
      correlation observed in our patients strengthens the fact that the genotype
      cannot be completely predictive of phenotype.

PMID- 21175092
TI  - Benign transient hyperphosphatasemia of infancy. A common benign scenario, a big
      concern for a pediatrician.
AB  - Benign transient hyperphosphatasemia of infancy (BTH) is a condition
      characterized by disproportionately high levels of serum alkaline phosphatase
      (SAP). We report 4 cases of healthy patients with an elevated SAP. The mean age
      of the patients was 33 (14-52) months, with three females and one male. All
      children had a normal physical exam and anthropometric measures. The maximum
      values of serum alkaline phosphatase recorded in the 4 patients were: 11900,
      6500, 9700 and 7600 UI/L respectively, with the rest of the laboratory exams and
      diagnostic images being normal. The clinical course of all the patients was
      favourable and no patient presented signs of symptoms of illness. Blood was drawn
      on 6 occasions in patients 1 and 5 occasions in the rest. Benign transient
      hyperphosphatasemia of infancy was diagnosed. It is important to know the
      characteristics of this condition to order the necessary amount of complementary
      studies.

PMID- 21175093
TI  - Scarcity despite wealth: osteopetrorickets.
AB  - Infantile malignant osteopetrosis is a rare and genetically autosomal recessive
      disease characterized by osteoclast malfunction. Decreased osteoclast-mediated
      bone resorption may be inadequate to maintain a normal serum calcium-phosphorus
      balance in the extracellular fluid. Consequently, despite markedly positive total
      body calcium balance, patients with osteopetrosis paradoxically could develop
      rickets. The concurrence of osteopetrosis and rickets has been termed
      "osteopetrorickets". We report here a 3-month-old boy who was diagnosed with
      osteopetrorickets with clinical features. Although osteopetrorickets is defined
      as a rare paradoxical feature of infantile malignant osteopetrosis in some
      studies, it seems to be more common than was previously known. Coexistence of
      rickets and osteopetrosis may have adverse effects on clinical response to stem
      cell transplantation. Therefore, a diagnosis of rickets must be considered in
      patients with osteopetrosis and then for better results, prior to the SCT, the
      rickets should be completely treated.

PMID- 21175094
TI  - Growth hormone therapy and the risk of tumor recurrence after brain tumor
      treatment in children.
AB  - To assess the effect of human growth hormone (hGH) therapy and other factors on
      tumor recurrence after treatment of pediatric brain tumors (BTs), we
      retrospectively analyzed data from 108 craniopharyngioma, medulloblastoma, and
      ependymoma patients. Risk factors were identified using multifactorial univariate
      regression analysis. Recurrences occurred in 41 and second malignant neoplasms in
      4 patients. There were significant correlations for completeness of tumor removal
      and recurrence-free survival (RFS). 13/44 hGH-treated and 28/59 non-hGH-treated
      children relapsed. This difference was found only for medulloblastomas and
      accounted for by higher rates of incomplete tumor removal in non-hGH patients.
      Craniopharyngioma recurrence correlated only with RFS. Malignant BT recurrence
      correlated with completeness of tumor removal, chemotherapy, and RFS. 4 children
      developed SMNs, 3/4 after hGH therapy. Our regression model yielded accurate
      within-sample prediction of recurrence for 90% of the study population. We
      conclude that hGH therapy after treatment of pediatric BTs does not increase
      tumor recurrence risk.

PMID- 21175095
TI  - Insulin resistance and the metabolic syndrome in obese children referred to an
      obesity center.
AB  - OBJECTIVE: The aim of this study was to describe insulin resistance and the
      metabolic syndrome in obese children and adolescents. SUBJECTS: The cohort
      consisted of 518 patients, 250 boys, 268 girls, age +/- sd: 11.8 +/- 3.2 years,
      BMIsds +/- sd: 2.94 +/- 0.5. A standard OGTT was performed. RESULTS: Impaired
      glucose tolerance was found in 9.4% of the boys and 5.5% of the girls. Impaired
      fasting glucose was found in 12.4% of the boys and 11.6% of the girls. The
      metabolic syndrome was present in 13.9% of children of 10 years or older. The
      proportion in which the metabolic syndrome was diagnosed was essentially not
      altered when pubertal groups were used instead of age groups. CONCLUSION: Both
      impaired fasting glucose and impaired glucose tolerance as well as the metabolic
      syndrome are highly prevalent among obese children and adolescents.

PMID- 21175096
TI  - Severe dietary protein sensitivity and hyperinsulinemic hypoglycemia in a patient
      with heterozygous mutation in HADH gene.

PMID- 21175097
TI  - Neonatal autoimmune hypothyroidism: a patient report.
AB  - BACKGROUND: Acquired primary hypothyroidism in neonates and infants under 3 years
      of age is very rare. Herein we report the case of an infant female affected by
      acquired autoimmune hypothyroidism. PATIENT REPORT: The infant was transferred to
      the Pediatric Clinic, University of Catania, Italy for evaluation of dysmorphic
      features, growth and motor retardation, and hypothyroidism on laboratory testing.
      Neonatal screening test for TSH and PKU was negative. An ultrasound scan showed a
      non-homogeneous thyroid gland which was increased in volume. Based on the
      laboratory results, the diagnosis of autoimmune hypothyroidism was made and L
      thyroxine treatment was initiated at 50 microg/day. CONCLUSIONS: Autoimmune
      hypothyroidism in infancy is rare, but early recognition and therapy are
      essential to prevent neurologic damage and growth deficits. In this patient we
      would like to underline the early age of appearance of autoimmune thyroid disease
      and the possible onset of pathologic events before birth.

PMID- 21175098
TI  - Adverse effect of phenytoin on glucocorticoid replacement in a child with adrenal
      insufficiency.
AB  - Chronic administration of antiepileptic agents such as phenytoin can increase
      clearance rates of cortisol and synthetic glucocorticoids through hepatic
      microsomal enzyme induction. However, data concerning an adverse interaction
      between antiepileptic and steroid drugs are scarce. We herein report an
      adolescent boy with primary adrenal insufficiency that developed glucocorticoid
      deficiency after added phenytoin treatment. The patient had an increased
      requirement for hydrocortisone replacement, and two episodes of vomiting,
      hyponatremia and mild hypoglycemia. His ACTH levels were markedly elevated.
      Fifteen days after stopping phenytoin, his serum ACTH concentration returned to
      normal range. Even though the hydrocortisone dose was gradually decreased,
      hyponatremia and vomiting have not recurred. In conclusion, we suggest that drugs
      such as phenytoin affecting hepatic clearance of synthetic glucocorticoids and
      mineralocorticoids should not be preferred for therapy in patients with adrenal
      insufficiency. If their use is vital, one should be aware of increased
      replacement requirements for steroid drugs, and patients should be closely
      monitored.

PMID- 21175099
TI  - Investigation of acquired von Willebrand Syndrome in children with
      hypothyroidism: reversal after treatment with thyroxine.
AB  - BACKGROUND: Acquired von Willebrand Syndrome (AvWS) is a rare bleeding disorder
      associated with various underlying conditions. Many case reports have been
      published so far on bleeding tendency in hypothyroidism resembling AvWS.
      OBJECTIVE: This study was designed to define the relationship between
      hypothyroidism and AvWS and to investigate the effects of L-thyroxine treatment.
      SUBJECTS: Twenty four hypothyroid patients were included in the study. Nineteen
      patients were evaluated during treatment, 5 patients were evaluated before
      hormone replacement. METHODS: Complete coagulation screening tests including
      levels of von Willebrand Factor antigen (vWF:Ag) and functional activity
      (vWF:RCo) were measured by thrombocyte aggregometer. RESULTS: We demonstrated low
      vWF:Ag and vWF:RCo in 13 patients. Two of the 13 patients were diagnosed as AvWS,
      while another 2 patients were diagnosed as hereditary vWD Type 1. The remaining
      patients are still being followed-up. CONCLUSION: We would like to attract the
      attention of paediatricians to the possibility of bleeding due to decreased
      activity of vWF in hypothyroid children.

PMID- 21175100
TI  - Kabuki syndrome and Crohn disease in a child with familial hypocalciuric
      hypercalcemia.
AB  - BACKGROUND: Familial hypocalciuric hypercalcemia (FHH) results from a mutation of
      the calcium sensing receptor (CASR) gene and typically presents as asymptomatic
      hypercalcemia with inappropriately low urinary calcium excretion and normal or
      mildly elevated levels of parathyroid hormone. OBJECTIVE: To describe a case of
      FHH associated with Kabuki syndrome and Crohn disease. METHOD: Genomic DNA was
      screened for CASR mutations and a retrospective chart review was performed.
      RESULTS: Heterozygosity was observed in exon 3, which encodes a portion of the
      extra-cellular domain. Sequencing revealed a n.476T>G nucleotide transversion,
      predicting a non-conservative substitution of arginine for leucine at codon 159
      (p.L159R). CONCLUSION: An association between Kabuki syndrome and autoimmune
      disease has been described in the literature, which may explain the connection
      between Kabuki syndrome and Crohn disease. However, it remains unclear if there
      is a link between FHH, Kabuki syndrome and Crohn disease in this case.

PMID- 21175101
TI  - Implications for incorporating simulation in nursing education.
AB  - The current intricately complex state of health care holds a multitude of
      challenges for the novice nurse in acquiring, developing, and maintaining
      standards of proficiency in clinical practice. This paper will explore the
      implications or reasons for incorporating simulation in nursing education for two
      primary reasons. First, simulation is an interactive teaching strategy designed
      for augmenting the learning process. Simulation is an example of active learning
      that engages the student to think through a situation then take action through
      the application of knowledge, and finally to self-reflect during the process of
      debriefing. Secondly, an increasing number of educational institutions have made
      the commitment to incorporate simulation technology into nursing curricula.

PMID- 21175102
TI  - Enhancing students' clinical experience: simple ideas that work.
AB  - This article provides ideas that an instructor can utilize to assist students
      with their educational objectives despite challenges in the clinical setting
      including student diversity, student anxiety and lack of instructor educational
      experience. The ideas are practical and include topics such as orientation day,
      communication, seating arrangements, self-awareness exercises, and bell ringers.
      The ideas can be modified by individual instructors to meet the specific needs of
      their students. The suggestions can then be adopted by the students to enhance
      their nursing careers.

PMID- 21175103
TI  - Anger management for nurses.

PMID- 21175104
TI  - Graves' disease: clinical pathophysiology, presentation and treatment options.

PMID- 21175105
TI  - DIGO: drug-induced gingival overgrowth. Part I: clinical features and
      pharmacology.

PMID- 21175106
TI  - Sexual assault in the workplace.
AB  - Women are sexually assaulted at an alarming rate, and the workplace is a frequent
      arena for assault. However, in recent decades, attention has been given to
      improving responses to sexual assault. Sexual assault is a frequent cause of
      injury and death for women in the United States. One in five American women admit
      they have experienced a completed rape during their lifetime. These estimates are
      conservative because sexual assault and sexual violence are both underreported
      and underprosecuted. Fear of job loss and discrimination are frequent reasons
      women do not report sexual assault in the workplace. Women are entering the
      workplace in greater numbers due in part to more single parent families and the
      depressed economy. Also, women are entering work environments that have
      traditionally been the domain of male workers: corporate headquarters, semi
      trucks, health care providers' offices, rural farms, and rural factories.
      Employers must have a plan to protect female employees and effectively address
      any incidents of sexual assault or violence. Occupational health nurses and nurse
      practitioners can assist both employees and employers to prevent sexual assault
      and resolve the aftermath of sexual assault. However, to accomplish this goal,
      occupational health nurses and nurse practitioners must be trained in sexual
      assault and violence response as well as preventive interventions.

PMID- 21175107
TI  - Shift work, light at night, and the risk of breast cancer.
AB  - Studies of the effect of shift work have identified several negative health
      outcomes, most notably breast cancer. Disruption of circadian rhythm by exposure
      to light at night has been identified as the mechanism likely responsible for
      this outcome. This article recommends that health care institutions work with
      occupational health nurses to develop and implement hazard communication and
      policies concerning shift work, exposure to light at night, and increased risk
      for negative health outcomes, particularly breast cancer.

PMID- 21175108
TI  - Changes in exodeviation following hyperopic correction in patients with
      intermittent exotropia.
AB  - PURPOSE: To evaluate changes in the angle of deviation after spectacle correction
      in patients who had hyperopia and intermittent exotropia (X(T)) and to determine
      whether the changes and surgical outcomes differ when compared with those of
      myopic and emmetropic X(T). METHODS: One hundred fourteen patients with X(T) were
      recruited and allocated into three groups: X(T) with hyperopia (group I; 38
      patients), X(T) with emmetropia (group II; 35 patients), and X(T) with myopia
      (group III; 41 patients). After at least 6 months wearing spectacles, changes in
      exodeviation were compared. The results of surgery based on the spectacle
      corrected distance angle and the ratios of accommodative convergence over
      accommodation (AC/A) were also assessed. RESULTS: With spectacle correction, the
      mean exodeviation increased significantly in group I, but did not change in
      groups II or III. Thirteen patients in group I (34%) showed a more than 10 prism
      diopters (PD) exotropic shift after wearing spectacles. The mean AC/A ratio in
      group I was 2.63 (PD/D), whereas in groups II and III the ratios were 4.03 and
      4.06, respectively. There was no difference in surgical results among the three
      groups. CONCLUSION: Although hyperopic correction in patients with X(T) resulted
      in a limited increase in exodeviation with a subnormal AC/A ratio, one-third of
      the patients experienced a significant increase in exodeviation. A spectacle
      correction trial should be considered before surgery in patients with hyperopia
      and X(T).

PMID- 21175109
TI  - Vitamin D.
AB  - There is growing awareness and evidence that vitamin D plays a pivotal role in
      maintaining health beyond its major biological function of enhancing calcium
      absorption and improving bone mineral density. Research findings suggest a strong
      relationship among a number of chronic diseases and vitamin D deficiency.
      Although vitamin D deficiency can occur across the age continuum, older adults
      with chronic diseases are particularly at risk. This article focuses on the role
      of vitamin D in maintaining health, current evidence linking vitamin D deficiency
      with chronic illness, and the importance of vitamin D supplementation.

PMID- 21175111
TI  - Global access to aging information and the gerontology healthy ageing portal.
AB  - Nursing, gerontology, and information communications technologies are well
      positioned to influence gerontological health system development by promoting
      global access to evidence-based best practices that facilitate local access to
      knowledge. Gerontological nurses, as members of the global community, are
      encouraged to become partners in promoting active and healthy aging. One
      mechanism is by participating in the development of a Gerontology Healthy Ageing
      Portal in the eGranary Digital Library, an "Internet in a Box"TM that provides
      offline digital resources to institutions and individuals where Internet access
      is lacking or undependable.

PMID- 21175110
TI  - Cognitive prescriptions.
AB  - Nonpathological cognitive declines occur with aging and negatively affect
      everyday functioning and reduce quality of life. Many older adults, aware of such
      cognitive changes, seek ways to bolster their cognitive functioning. Evidence
      based on the cognitive aging literature supports a number of factors associated
      with cognitive functioning. These factors include physical exercise, intellectual
      exercise, nutrition, sleep hygiene, social interaction, and mood and emotional
      state. These factors can be manipulated and woven together by nurses and other
      health professionals to develop an easy-to-use, non-invasive cognitive
      prescription for improving the cognitive health of older adults. An example and
      directions for developing and implementing cognitive prescriptions are described.

PMID- 21175112
TI  - The positive impact of preceptors on recruitment and retention of RNs in long
      term care.
AB  - Nearly 100,000 nursing positions in long-term care (LTC) are vacant on any given
      day, and the nurse turnover rate exceeds 50%. In addition, recruitment of and
      orientation programs for new nurses are costly for facilities. Preceptor programs
      have been successful in recruitment and retention of acute care nurses, but no
      recent literature addresses preceptor programs in LTC. The Expanding the Teaching
      Nursing Home Culture in the State of Illinois project explored the development of
      a preceptor program to fit the LTC environment in which an RN was chosen to serve
      as the preceptor and mentor and orient all new nurses. Although the LTC
      environment presents social and economic challenges, a structured preceptor
      program allows nurses new to LTC to meet these challenges. By retaining nurses,
      residents receive continuity of care. This strategy for recruitment and retention
      of nurses results in professional growth, competent and stable staff, and a
      stronger bottom line.

PMID- 21175113
TI  - Retinal detachment despite aggressive management of aggressive posterior
      retinopathy of prematurity.
AB  - Posterior retinopathy of prematurity (ROP) is unusual in its atypical features
      and its aggressive, rapidly progressive course. It is more difficult to recognize
      and to treat, with many of these eyes progressing to retinal detachment despite
      multiple treatments with laser or cryotherapy. The authors present a case of
      aggressive posterior ROP refractory to multiple laser treatment. This patient was
      successfully treated with intravitreal bevacizumab, but required repeat treatment
      4 months later. The second injection with bevacizumab was followed by progression
      to retinal detachment requiring surgery. The patient remains stable after
      surgery.

PMID- 21175114
TI  - Increased intracranial pressure in patients with cystinosis.
AB  - Patients with cystinosis have risk factors known to be associated with secondary
      increased intracranial pressure. The authors report a series of patients with
      cystinosis and describe their experience in the diagnosis and management of
      increased intracranial pressure in this population. The ophthalmologist should be
      aware of this vision-threatening association.

PMID- 21175115
TI  - Duane retraction syndrome type I, Marcus Gunn jaw-winking and crocodile tears in
      the same eye.
AB  - Duane retraction syndrome type I, Marcus Gunn jaw-winking and crocodile tears are
      all syndromes of congenital aberrant innervation. The authors describe a 17-month
      old boy with Duane retraction syndrome type I, Marcus Gunn Jaw-winking, and
      crocodile tears in the same eye and discuss the proposed mechanisms of these
      conditions.

PMID- 21175116
TI  - Retinocytoma shows lack of response to chemoreduction.
AB  - The authors report a case of retinocytoma showing no response to chemoreduction.
      A 30-month-old girl presented with Group B multifocal retinoblastoma in the right
      eye and Group E retinoblastoma in the left eye. After the first cycle of
      chemotherapy (vincristine [0.9 mg/m(2)], carboplatin [336 mg/m(2)], and etoposide
      [90 mg/m(2)]), there was remarkable reduction in the tumor size in the left eye,
      whereas the right eye tumors did not regress and were diagnosed as
      retinocytomas/retinomas. Retinocytoma/retinoma shows little to no response to
      chemoreduction.

PMID- 21175117
TI  - Macular hole in a newborn associated with forceps delivery.
AB  - A newborn who had familial high myopia presented with bilateral dense vitreous
      hemorrhage after forceps delivery. Vitrectomy in the right eye revealed a macular
      hole surrounded by pigmented cells. After subsequent surgery, the macular hole
      healed and remained closed during 10 years of follow-up, but profound amblyopia
      persisted. Macular hole is a possible complication of forceps delivery.
      Vitrectomy associated with inner limiting membrane peeling and gas tamponade was
      effective in closing macular hole in a newborn but was unable to prevent
      amblyopia.

PMID- 21175118
TI  - Sleep interventions for the treatment of depression.
AB  - Sleep disturbances are common in depressed patients. Insomnia may predate the
      onset of major depression, increases the likelihood of a depressive relapse, and
      is associated with an impaired response to treatment. Benzodiazepine drugs may
      have inherent antidepressant effects; thus, these and other sedative-hypnotic
      drugs can be beneficial for treating insomnia in depressed patients and may
      enhance the overall effectiveness of antidepressant drugs. Sedating
      antidepressant drugs are used for treating primary insomnia, but their sleep
      promoting effects have been demonstrated primarily in depressed patients. Several
      second-generation antipsychotic drugs are used in low doses to promote sleep, but
      they also have inherent antidepressant effects. Cognitive-behavioral therapy
      targeting insomnia can effectively enhance the response to antidepressant
      medication. Sleep deprivation, which is also associated with a transient
      antidepressant effect, is difficult to use in routine clinical practice but might
      be an appropriate strategy for treatment-resistant forms of depression.

PMID- 21175119
TI  - Meeting the mental health needs of the aging veteran population.
AB  - The growth in the veterans population parallels the graying of America,
      accompanied by an increasing need for health care and mental health services from
      the U.S. Department of Veterans Affairs (VA) health care system. With the
      incidence of posttraumatic stress disorder (PTSD) rising in veterans of the wars
      in Iraq and Afghanistan and the already strained mental health resources in use
      by veterans with persistent PTSD from previous wars, the VA mental health system
      is and will continue to be in overload. In addition, recent research has noted an
      increased incidence of dementia in veterans with PTSD. The VA's long-term care
      facilities cannot meet their current demands, nevermind provide support for
      veterans with cognitive deficits who can no longer be cared for at home. It is
      imperative that immediate measures be taken to strengthen resources for research,
      manpower, and training to accommodate the future mental health needs of our aging
      veterans.

PMID- 21175120
TI  - Development of the Edmonson Psychiatric Fall Risk Assessment Tool.
AB  - The purpose of this study was to develop a fall risk assessment instrument for
      the inpatient psychiatric population. Nine risk factors were identified through a
      review of the literature. The instrument was applied retrospectively to patient
      records, and the percentage of those who fell who triggered each of the items in
      each domain was calculated. The expected value of the population and weighting
      system were established. The Morse Fall Scale and Edmonson Psychiatric Fall Risk
      Assessment Tool (EPFRAT) were administered simultaneously to inpatient
      psychiatric patients. Sensitivity of the EPFRAT was 0.63, compared with 0.49 for
      the Morse Fall Scale; specificity of the EPFRAT was 0.86, compared with 0.85 for
      the Morse Fall Scale. Initial psychometric testing of the EPFRAT indicates the
      instrument is more sensitive in assessing fall risk in the acutely ill
      psychiatric population than those currently available. Additional psychometric
      testing is needed to determine the reliability and validity of the EPFRAT.

PMID- 21175121
TI  - Transforming the culture of caring.
AB  - Direct care staff struggle with the decision of when to physically intervene with
      patients. There is a widely held belief that they are expected to place
      themselves in danger of harm to prevent patients from hurting themselves or
      others. In this acute mental health care setting, an educational program was
      developed, using principles of adult and transformational learning, to dispel the
      idea that getting hurt is part of the job. The Staying Safe program strongly
      discourages staff from physically intervening alone and promotes staff getting
      enough help and having a plan. Staff are encouraged to interact with patients in
      helpful ways and to respond to patient requests in ways that do not increase
      frustration or evoke anger. There has been a positive response to the training
      program, evidenced by changes in the way staff think about their jobs and a
      reduction in the number of assaults and injuries to staff.

PMID- 21175122
TI  - Perceptions of successful aging in Black older adults.
AB  - Successful aging is important; however, there is a lack of knowledge on how to
      promote successful aging in Black older adults. In this study, which examined
      Black older adults' perceptions of successful aging, a cross-sectional
      descriptive design was used to examine the psychometric properties of the
      Successful Aging Inventory and qualitative characteristics of successful aging in
      100 Black older adults. The participants' responses to an open-ended question,
      "What does successful aging mean to you?" revealed relevant aspects of successful
      aging. Six broad categories emerged: Independence/Ability, Health, Mindset,
      Activity/Service, Family, and Spirituality. These categories suggest foci for
      potential interventions to promote successful aging in Black older adults.

PMID- 21175123
TI  - Understanding bacterial cell-cell communication with computational modeling.

PMID- 21175125
TI  - Folding and unfolding of light-triggered beta-hairpin model peptides.
AB  - Ultrafast spectroscopy in the visible and mid-infrared is used to study the
      reaction dynamics of two light-triggered model peptides containing an azobenzene
      derivative as a switching element. One model peptide, the AzoTrpZip2, forms a
      beta-hairpin structure in the cis form of the chromophore. This peptide is
      compared to the core structure consisting of the chromophore and the two flanking
      amino acid residues, used as a minimal model. This combination of experiments
      performed in different spectral ranges on peptides of different sizes allows for
      improved insight into light triggered reaction dynamics. The kinetics observed
      for the core structure are directly connected to the switching process of the
      chromophore and are finished on the 10 ps time scale. The trans-to-cis reaction
      of AzoTrpZip2, leading to the formation of the beta-hairpin structure involves
      ultrafast processes on the 100 ps time scale, which are directly related to the
      relaxation of the strain between the isomerized molecular switch and the two
      peptide strands. IR-signatures characteristic for changes in interstrand
      interactions are absent on the <1 ns time scale. Thus folding into the beta
      hairpin structure occurs on a much longer time scale. In the cis-to-trans
      unfolding reaction, all IR signatures related to changes in interstrand
      interactions occur within 1 ns, in a time range where visible spectroscopy
      reveals the final decay of the intramolecular strain. Apparently unfolding of
      AzoTrpZip2 is to a large extent a fast, driven process.

PMID- 21175124
TI  - Mobilization of soil-bound residue of organochlorine pesticides and polycyclic
      aromatic hydrocarbons in an in vitro gastrointestinal model.
AB  - A previous study on mobilization of organochlorine pesticides (OCPs) in
      contaminated soils from the field revealed that the total amount of OCPs measured
      in digestive fluid and chyme of an in vitro gastrointestinal model was higher
      than the quantity directly extracted using a solvent extraction without
      digestion, providing a clue that the bound residue of OCPs might be mobilized.
      This hypothesis was tested in this study for both OCPs and polycyclic aromatic
      hydrocarbons (PAHs). Three contaminated surface soil samples with different
      organic carbon (OC) contents were collected from the field, and extracted with a
      solvent with and without digestion in an in vitro gastrointestinal model. It was
      found that bound residues of OCPs and PAHs were mobilized to a certain extent
      during digestion. The ratios of the mobilized bound residues over the total
      quantities extracted after digestion (R(b)) varied from 0 to 0.96 for individual
      compounds. The R(b) was positively correlated with OC content. Among the five
      constitutes of digestive juice, bile salt was the only one that served to
      mobilize the bound residues and the extractability of bile salt was constant over
      a concentration range from 2 to 20 mg/mL. The mobilization process followed
      typical first-order kinetics. The calculated rate constants suggest that
      mobilization was fast and 90% of extracted bound residues of OCPs and PAHs were
      mobilized within 2.4 and 4.8 h, respectively.

PMID- 21175126
TI  - Effect of nonadditive repulsive intermolecular interactions on the light
      scattering of concentrated protein-osmolyte mixtures.
AB  - The static light scattering of three globular proteins, bovine serum albumin,
      ovalbumin, and ovomucoid, and binary mixtures of each protein and trimethylamine
      oxide (TMAO) containing between 10 and 70% protein, were measured as a function
      of total weight per volume concentration up to 100 g/L. The observed dependence
      of scattering upon concentration may be accounted for quantitatively by an
      effective hard sphere model incorporating an extension that takes into account
      the nonadditive nature of the repulsive intermolecular interaction between
      protein and TMAO.

PMID- 21175128
TI  - Monomer-resolved simulations of cluster-forming dendrimers.
AB  - We present results of monomer-resolved Monte Carlo simulations for a system of
      amphiphilic dendrimers of the second generation. Our investigations validate a
      coarse-grained level description based on the zero-density limit effective pair
      interactions for low and intermediate densities, which predicted the formation of
      stable, finite aggregates in the fluid phase. Indeed, we find that these systems
      form a homogeneous fluid for low densities, which, on increasing the density,
      spontaneously transforms into a fluid of clusters of dendrimers. Although these
      clusters are roughly spherical in nature for intermediate densities, more complex
      structures are also detected for the highest densities considered.

PMID- 21175127
TI  - Biphasic regulation of intracellular calcium by gemfibrozil contributes to
      inhibiting L6 myoblast differentiation: implications for clinical myotoxicity.
AB  - Gemfibrozil is the most myotoxic fibrate drug commonly used for dyslipidemia, but
      the mechanism is poorly understood. The current study revealed that gemfibrozil
      inhibits myoblast differentiation through the regulation of intracellular calcium
      ([Ca(2+)]i) as revealed in L6 myoblasts by use of laser scan confocal microscopy
      and flow cytometry using Fluo-4 AM as a probe. Gemfibrozil at 20-400 MUM, could
      regulate [Ca(2+)]i in L6 cells in a biphasic manner, and sustained reduction was
      observed when the concentration reached 200 MUM. Inhibition of L6 differentiation
      by gemfibrozil was concentration-dependent with maximal effect noted between 200
      and 400 MUM, as indicated by creatine kinase activities and the differentiation
      index, respectively. In differentiating L6 myoblasts, gemfibrozil at
      concentrations below 400 MUM led to no significant signs of apoptosis or
      cytotoxicity, whereas differentiation, inhibited by 200 MUM gemfibrozil, was only
      partially recovered. A good correlation was noted between gemfibrozil
      concentrations that regulate [Ca(2+)]i and inhibit L6 myoblasts differentiation,
      and both are within the range of total serum concentrations found in the clinic.
      These data suggest a potential pharmacodynamic effect of gemfibrozil on
      myogenesis as a warning sign, in addition to the complex pharmacokinetic
      interactions. It is also noteworthy that mobilization of [Ca(2+)]i by gemfibrozil
      may trigger complex biological responses besides myocyte differentiation.
      Information revealed in this study explores the mechanism of gemfibrozil-induced
      myotoxicity through the regulation of intracellular calcium.

PMID- 21175129
TI  - Quasi-steady-state voltammetry of rapid electron transfer reactions at the
      macroscopic substrate of the scanning electrochemical microscope.
AB  - We report on a novel theory and experiment for scanning electrochemical
      microscopy (SECM) to enable quasi-steady-state voltammetry of rapid electron
      transfer (ET) reactions at macroscopic substrates. With this powerful approach,
      the substrate potential is cycled widely across the formal potential of a redox
      couple while the reactant or product of a substrate reaction is amperometrically
      detected at the tip in the feedback or substrate generation/tip collection mode,
      respectively. The plot of tip current versus substrate potential features the
      retraceable sigmoidal shape of a quasi-steady-state voltammogram although a
      transient voltammogram is obtained at the macroscopic substrate. Finite element
      simulations reveal that a short tip-substrate distance and a reversible substrate
      reaction (except under the tip) are required for quasi-steady-state voltammetry.
      Advantageously, a pair of quasi-steady-state voltammograms is obtained by
      employing both operation modes to reliably determine all transport,
      thermodynamic, and kinetic parameters as confirmed experimentally for rapid ET
      reactions of ferrocenemethanol and 7,7,8,8-tetracyanoquinodimethane at a Pt
      substrate with ~0.5 MUm-radius Pt tips positioned at 90 nm-1 MUm distances.
      Standard ET rate constants of ~7 cm/s were obtained for the latter mediator as
      the largest determined for a substrate reaction by SECM. Various potential
      applications of quasi-steady-state voltammetry are also proposed.

PMID- 21175130
TI  - Aggregation and homogenization, surface charge and structural change, and
      inactivation of mushroom tyrosinase in an aqueous system by
      subcritical/supercritical carbon dioxide.
AB  - The subcritical/supercritical carbon dioxide (SS CO(2)) has gained considerable
      attention in green chemistry industry for its advantage as nontoxic,
      nonflammable, and inexpensive. The effects of SS CO(2) treatments on aggregation
      and homogenization, surface charge, secondary and tertiary structure, and
      activity of mushroom tyrosinase in an aqueous system were investigated using a
      number of methods including dynamic light scattering (DLS), zeta potential
      measurement, circular dichroism (CD) spectropolarimeter, and spectrofluorometer.
      With a treatment time of 20 min, three treatment temperatures (35, 45, and 55 
      degrees C) and four pressures (5, 8, 12, and 15 MPa) had been selected. The
      aggregation and homogenization of the globular protein particles was induced by
      SS CO(2) as suggested by the particle size distribution (PSD) patterns that were
      closely related to the pressure and temperature. The surface charge of the
      tyrosinase decreased following the SS CO(2) treatments, and its variation
      tendency shows a favorable consistency with that of its PSD patterns. The alpha
      helix conformation in secondary structure and fluorescence intensity reflecting
      tertiary structure also decreased, together with the lambda(max) red-shifted with
      the increasing pressure. The results also indicated that SS CO(2) could enhance
      inactivation effect of the temperature on the tyrosinase with its lowest residual
      activity being about 60% under the condition of 8 MPa, 55  degrees C, and 20 min
      treatment time. The loss in the activity of the tyrosinase was correlated to its
      aggregation and homogenization effect induced by SS CO(2), which led to the
      change of surface charge as well as secondary and tertiary structure.

PMID- 21175131
TI  - Antiangiogenic potential of three triterpenic acids in human liver cancer cells.
AB  - Three triterpenic acids, oleanolic acid, ursolic acid and maslinic acid, at 2 or
      4 MUmol/L were used to study their antiangiogenic potential in human liver cancer
      Hep3B, Huh7 and HA22T cell lines. The effects of these compounds upon the level
      and/or expression of hypoxia-inducible factor (HIF)-1alpha, basic fibroblast
      growth factor (bFGF), vascular endothelial growth factor (VEGF), interleukin (IL)
      8, urokinase plasminogen activator (uPA), reactive oxygen species (ROS), nitric
      oxide (NO) and cell invasion and migration were examined. Results showed that
      these triterpenic acids at 4 MUmol/L significantly suppressed HIF-1alpha
      expression in three cell lines (P < 0.05); and these compounds at test doses
      failed to affect bFGF expression (P > 0.05). Three triterpenic acids dose
      dependently decreased production and expression of VEGF and IL-8, retained
      glutathione level, lowered ROS and NO levels, and declined cell invasion and
      migration in test cell lines (P < 0.05). These compounds also dose-dependently
      reduced uPA production and expression in Hep3B and Huh7 cell lines (P < 0.05);
      but these agents only at 4 MUmol/L significantly suppressed uPA production and
      expression in HA22T cells (P < 0.05). These findings suggest that these
      triterpenic acids are potent antiangiogenic agents to retard invasion and
      migration in liver cancer cells.

PMID- 21175133
TI  - Low symmetry phthalocyanines and their analogues.

PMID- 21175132
TI  - Atomic force microscopy reveals drebrin induced remodeling of f-actin with
      subnanometer resolution.
AB  - We show by high-resolution atomic force microscopy analysis that drebrin A (a
      major neuronal actin binding protein) induced F-actin structural and mechanical
      remodeling involves significant changes in helical twist and filament stiffness
      (+55% persistence length). These results provide evidence of a unique mechanical
      role of drebrin in the dendrites, contribute to current molecular-level
      understanding of the properties of the neuronal cytoskeleton, and reflect the
      role of biomechanics at the nanoscale, to modulate nanofilament-structure
      assemblies such as F-actin.

PMID- 21175134
TI  - Extraordinary optical transmission brightens near-field fiber probe.
AB  - Near-field scanning optical microscopy (NSOM) offers high optical resolution
      beyond the diffraction limit for various applications in imaging, sensing, and
      lithography; however, for many applications the very low brightness of NSOM
      aperture probes is a major constraint. Here, we report a novel NSOM aperture
      probe that gives a 100* higher throughput and 40* increased damage threshold than
      conventional near-field aperture probes. These brighter probes facilitate near
      field imaging of single molecules with apertures as small as 45 nm in diameter.
      We achieve this improvement by nanostructuring the probe and by employing a novel
      variant of extraordinary optical transmission, relying solely on a single
      aperture and a coupled waveguide. Comprehensive electromagnetic simulations show
      good agreement with the measured transmission spectra. Due to their significantly
      increased throughput and damage threshold, these resonant configuration probes
      provide an important step forward for near-field applications.

PMID- 21175135
TI  - Optical chemosensor for Ag+, Fe3+, and cysteine: information processing at
      molecular level.
AB  - A thiacalix[4]arene based chemosensor 3 bearing two pyrene groups has been
      synthesized which demonstrates ratiometric sensing with Ag(+) and fluorescence
      quenching with Fe(3+) ions in mixed aqueous media. The 'in situ' prepared Ag(+)
      and Fe(3+) complexes showed high selectivity toward cysteine. The molecular
      switching between three chemical inputs (Ag(+), Fe(3+), cysteine) results in
      various molecular logic gates which have been integrated sequentially to generate
      a sequential information processing device.

PMID- 21175137
TI  - Relative humidity sensors based on an environment-sensitive fluorophore in
      hydrogel films.
AB  - A fluorescence-based sensing scheme exploiting an environment-sensitive
      fluorophore embedded in a hydrogel has been developed for measurement of relative
      humidity (RH). The fluorophore, dapoxyl sulfonic acid (DSA), is incorporated into
      two different hydrogel films, agarose and a copolymer of acrylamide and 2
      (dimethylamino)ethyl methacrylate (DMAEM) cross-linked with N,N'
      methylenebisacrylamide. The swelling and contracting of the hydrogels in response
      to relative humidity alters the polarity of the environment of DSA, stimulating a
      shift in the emission wavelength. From 0 to 100% RH, acrylamide-DMAEM sensors
      exhibited a 40 and 15 nm wavelength shift in still air and flowing gas,
      respectively. Agarose sensors showed a 40 nm wavelength shift from 0 to 100% RH
      in still air and a 30 nm shift from 0 to 70% RH in flowing gas. Response times
      for both sensors were 15 min in still air and less than 5 min in flowing gas. The
      sensing approach is straightforward and cost-effective, yields sensors with
      characteristics suitable for commercial measurement of RH (i.e., sensitivity,
      response times, reproducibility), and allows ease of adaptability to specific RH
      measurement requirements. The results support the potential extension of the
      method to a wide variety of analytes in the vapor phase and aqueous solution by
      incorporation of functionalized "smart" hydrogels.

PMID- 21175136
TI  - Solid-state NMR and density functional theory studies of ionization states of
      thiamin.
AB  - Thiamin diphosphate (ThDP) is a key coenzyme in sugar metabolism. The 4'
      aminopyrimidine ring of ThDP cycles through several ionization and tautomeric
      states during enzyme catalysis, but it is not fully understood which states are
      adopted during the individual steps of the catalytic cycle. Thiamin has been
      synthesized with labels selectively inserted into the C2 and C6' positions, as
      well as into the amino group, creating [C2, C6'-(13)C(2)] thiamin and [N4'-(15)N]
      thiamin. Magic-angle spinning (MAS) NMR spectroscopy has been employed to record
      the (13)C and (15)N chemical shift anisotropy (CSA) tensors for C2, C6', and N4'
      atoms. Our results indicate that the isotropic chemical shifts as well as the
      principal components of the (13)C and (15)N CSA tensors are very sensitive to the
      protonation states in these compounds and, therefore, permit differentiating
      between the two ionization states, 4-aminopyrimidine and 4-aminopyrimidinium.
      Using density functional theory (DFT), we have calculated the magnetic shielding
      anisotropy tensors of C2, C6', and N4' and found excellent agreement between the
      computed and the experimental tensors. Our findings indicate that MAS NMR
      spectroscopy in conjunction with DFT calculations is a sensitive probe of
      ionization states in the thiamin cofactor. The results of this study will serve
      as a guide for characterization of ionization and tautomeric states of thiamin in
      complexes with thiamin-dependent enzymes.

PMID- 21175138
TI  - An atom-economic synthesis of nitrogen heterocycles from alkynes.
AB  - A robust route to 2,4-disubstituted pyrrole heterocycles relying upon a cascade
      reaction is reported. The reaction benefits from operational simplicity: it is
      air and moisture tolerant and is performed at ambient temperature. Control over
      the reaction conditions provides ready access to isopyrroles, 2,3,4
      trisubstituted pyrroles, and 3-substituted pyrollidin-2-ones.

PMID- 21175139
TI  - In situ analysis and structural elucidation of sainfoin (Onobrychis viciifolia)
      tannins for high-throughput germplasm screening.
AB  - A rapid thiolytic degradation and cleanup procedure was developed for analyzing
      tannins directly in chlorophyll-containing sainfoin ( Onobrychis viciifolia )
      plants. The technique proved suitable for complex tannin mixtures containing
      catechin, epicatechin, gallocatechin, and epigallocatechin flavan-3-ol units. The
      reaction time was standardized at 60 min to minimize the loss of structural
      information as a result of epimerization and degradation of terminal flavan-3-ol
      units. The results were evaluated by separate analysis of extractable and
      unextractable tannins, which accounted for 63.6-113.7% of the in situ plant
      tannins. It is of note that 70% aqueous acetone extracted tannins with a lower
      mean degree of polymerization (mDP) than was found for tannins analyzed in situ.
      Extractable tannins had between 4 and 29 lower mDP values. The method was
      validated by comparing results from individual and mixed sample sets. The tannin
      composition of different sainfoin accessions covered a range of mDP values from
      16 to 83, procyanidin/prodelphinidin (PC/PD) ratios from 19.2/80.8 to 45.6/54.4,
      and cis/trans ratios from 74.1/25.9 to 88.0/12.0. This is the first high
      throughput screening method that is suitable for analyzing condensed tannin
      contents and structural composition directly in green plant tissue.

PMID- 21175140
TI  - Highly enantioselective nitrone cycloadditions with 2-alkenoyl pyridine N-oxides
      catalyzed by Cu(II)-BOX complexes.
AB  - Enantioselective nitrone cycloadditions with 2-alkenoyl pyridine N-oxides as
      dipolarophiles have been reported. The reaction is catalyzed by Cu(II)-BOX
      complexes to give the expected isoxazolidine products with high diastereo- and
      enantioselectivity.

PMID- 21175141
TI  - 1,3-Dipolar cycloaddition-decarboxylation reactions of an azomethine ylide with
      isatoic anhydrides: formation of novel benzodiazepinones.
AB  - A nonstabilized azomethine ylide reacts with a wide range of substituted isatoic
      anhydrides to afford novel 1,3-benzodiazepin-5-one derivatives, which are
      generally isolated in high yield. The transformations involve 1,3-dipolar
      cycloaddition reactions of the ylide with the anhydrides to give transient, and
      in a representative case spectroscopically observable, oxazolidine intermediates
      that undergo ring-opening-decarboxylation-ring-closing reaction cascades to yield
      the 1,3-benzodiazepin-5-one products.

PMID- 21175142
TI  - A generalized free energy perturbation theory accounting for end states with
      differing configuration space volume.
AB  - We present a generalized free energy perturbation theory that is inspired by
      Monte Carlo techniques and based on a microstate description of a transformation
      between two states of a physical system. It is shown that the present free energy
      perturbation theory stated by the Zwanzig equation follows as a special case of
      our theory. Our method uses a stochastic mapping of the end states that
      associates a given microstate from one ensemble with a microstate from the
      adjacent ensemble according to a probability distribution. In contrast, previous
      free energy perturbation methods use a static, deterministic mapping that
      associates fixed pairs of microstates from the two ensembles. The advantages of
      our approach are that end states of differing configuration space volume can be
      treated easily also in the case of discrete configuration spaces and that the
      method does not require the potentially cumbersome search for an optimal
      deterministic mapping. The application of our theory is illustrated by some
      example problems. We discuss practical applications for which our findings could
      be relevant and point out perspectives for further development of the free energy
      perturbation theory.

PMID- 21175144
TI  - Oxidation of alpha-oxo-oximes to nitrile oxides with hypervalent iodine reagents.
AB  - Upon reaction with PhI(OAc)(2), alpha-oxo-aldoximes are oxidized to alpha-oxo
      nitrile oxides, while alpha-oxo-ketoximes are converted into nitrile oxides via
      the oxidative cleavage of the carbonyl-imino sigma bond. The nitrile oxides thus
      formed were trapped with norbornene or styrene in good yield. alpha,alpha'-Dioxo
      ketoximes react less efficiently.

PMID- 21175143
TI  - Rh(III)-catalyzed oxidative coupling of unactivated alkenes via C-H activation.
AB  - Oxime directed aromatic C-H bond activation and oxidative coupling to alkenes is
      reported using a cationic Rh(III) catalyst. Significantly, the method can be used
      to oxidatively couple unactivated, aliphatic alkenes.

PMID- 21175146
TI  - Gold catalyzed carbocyclization of dienyl acetates to construct
      mutifunctionalized 3-vinyl cyclohexanol derivatives.
AB  - A convenient new method was developed to construct six-membered 3
      vinylcyclohexanols (and piperidine products) and 6-oxabicyclo[3.2.1]octan-7-one
      derivatives with high diastereoselectivities from 1,6-dienyl acetates via gold
      catalysis. The reaction proceeded through the nucleophilic addition of the
      alkenes onto the allylic cation group via a 6-endo-trig process. The substrate's
      structure affected the configuration orientation of the allylic cation group in a
      boatlike transition state, which afforded either the trans-cyclohexanols or cis
      piperidine derivatives.

PMID- 21175145
TI  - An insight into the radical thiol/yne coupling: the emergence of arylalkyne
      tagged sugars for the direct photoinduced glycosylation of cysteine-containing
      peptides.
AB  - An explorative study of the Thiol-Yne Coupling (TYC) reaction has been carried
      out using an aliphatic (1-octyne) and an aromatic alkyne (phenylacetylene) and
      two alkanethiols (methyl thioglycolate and N-acetyl-L-cysteine methyl ester). The
      outcomes of the TYC reactions strongly depend on the experimental conditions
      (e.g., temperature, solvent, and alkyne/thiol ratio), but these can be properly
      adjusted to achieve selective production of either mono- or bis-coupling
      products. With respect to 1-octyne, phenylacetylene undergoes notably easier
      radical hydrothiolation, further showing a notably higher aptitude for
      monohydrothiolation exclusive of bis-hydrothiolation. The overall findings were
      exploited in glycosylation of cysteine derivatives as well as of cysteine
      containing peptides. A sugar featuring an arylacetylene moiety gave rise to a
      true click-reaction, that is, glycosylation of the tripeptide glutathione in its
      native form, by means of virtually equimolar amounts of reagents. This reaction
      was successfully applied, under physiological conditions, to a cysteine
      containing nonapeptide with marked advantages over the analogous Thiol-Ene
      Coupling (TEC) derivatization. A TYC/TEC sequence affording bis-armed cysteine
      derivatives through dual functionalization of an alkynyl sugar was additionally
      devised.

PMID- 21175147
TI  - Synthesis of orthogonally protected disulfide bridge mimetics.
AB  - Concise routes to four orthogonally protected, enantiopure disulfide bridge
      mimetics are reported. These four dicarba analogues possess an alkyne, an (E)
      alkene, a (Z)-alkene, and an alkane as substitutes for the disulfide bridge.
      Selective deprotection of one of these mimetics is also illustrated.

PMID- 21175148
TI  - Peptidyl N,N-bis(2-mercaptoethyl)-amides as thioester precursors for native
      chemical ligation.
AB  - With two beta-mercaptoethyl groups on the N, a tertiary amide of structure 1 is
      always poised for intramolecular thioesterification however it flips about the C
      N bond. It is shown that a peptide with such a C-terminal N,N-bis(2
      mercaptoethyl)-amide (BMEA) can be used directly for native chemical ligation
      (NCL). These BMEA peptides are easily prepared with standard Fmoc-solid phase
      peptide synthesis protocols, thus giving a very convenient access to the
      thioester components for NCL.

PMID- 21175149
TI  - Copper-catalyzed intramolecular C-N bond formation: a straightforward synthesis
      of benzimidazole derivatives in water.
AB  - A straightforward, efficient, and more sustainable copper-catalyzed method has
      been developed for intramolecular N-arylation providing the benzimidazole ring
      system. With Cu(2)O (5 mol %) as the catalyst, DMEDA (10 mol %) as the ligand,
      and K(2)CO(3) as the base, this protocol was applied to synthesize a small
      library of benzimidazoles in high yields. Remarkably, the reaction was
      exclusively carried out in water, rendering the methodology highly valuable from
      both environmental and economical points of view.

PMID- 21175150
TI  - Schinarisanlactone A, a new bisnortriterpenoid from Schisandra arisanensis.
AB  - A novel triterpenoid, schinarisanlactone A (1), was isolated from the fruits of
      Schisandra arisanensis. Compound 1 possesses an unprecedented skeleton having a
      5/7/7/5/7/5/6/5-fused octacyclic ring system. The structure of 1 was determined
      by 2D NMR techniques (COSY, HMQC, HMBC, and NOESY) and was confirmed by X-ray
      crystallographic analysis. Schinarisanlactone A (1) exhibited significant anti
      HIV activity.

PMID- 21175151
TI  - Highly water-soluble neutral BODIPY dyes with controllable fluorescence quantum
      yields.
AB  - A series of novel highly water-soluble neutral BODIPY dyes have been obtained by
      functionalization of BODIPY dyes with branched oligo(ethylene glycol)methyl ether
      groups at positions 8, 2 and 6 or 4 and 4'. Use of an ortho-substituent group of
      branched oligo(ethylene glycol)methyl ether on the meso-phenyl ring of BODIPY
      dyes and replacement of the fluorine atoms of BODIPY dyes at positions 4 and 4'
      with methyloxy or ethynyl subunits significantly enhance fluorescence quantum
      yields of BODIPY dyes.

PMID- 21175152
TI  - Organocatalytic stereoselective epoxidation of trisubstituted acrylonitriles.
AB  - The first diastereospecific and enantioselective epoxidation of trans-2-aroyl-3
      arylacrylonitriles by means of the commercially available diaryl L-prolinol/tert
      butyl hydroperoxide system has been developed. These diversely functionalized
      epoxides were obtained in excellent yield (up to 99%), complete
      diastereoselectivity for the trans-isomer, and good enantioselectivity (up to 84%
      ee). Highly enantioenriched epoxides can be easily obtained after a single
      crystallization (ee > 90%).

PMID- 21175153
TI  - Synthesis of phantasmidine.
AB  - Reaction of 6-chloro-2-fluoro-3-pyridineacetamide with 1,2
      bis(trimethylsilyloxy)cyclobutene in ether saturated with hydrogen chloride
      afforded the keto amide in 85% yield. In the key step, treatment of the keto
      amide with aqueous KOH in t-BuOH resulted in a tandem intramolecular aldol
      reaction-intramolecular nucleophilic aromatic substitution sequence to give the
      tetracylic lactam in 46% yield. Reduction of the lactam with BH(3) in THF gave
      phantasmidine in 67% yield.

PMID- 21175154
TI  - Synthesis of isoxazoline N-oxides via [hydroxy(tosyloxy)iodo]benzene (HTIB)
      mediated oxidative N-O coupling.
AB  - An HTIB mediated oxidative N-O coupling strategy for the synthesis of some
      isoxazoline N-oxide derivatives from beta-hydroxyketoximes is described, along
      with a comparative study of the efficiency of N-O coupling in two different
      solvents. A plausible mechanism for the conversion is proposed.

PMID- 21175155
TI  - Transition-metal-free O-, S-, and N-arylation of alcohols, thiols, amides,
      amines, and related heterocycles.
AB  - A new protocol for the Ullmann-type arylation process of different aromatic
      heterocycles without any transition-metal catalyst, implying the use of a
      combination of an excess of potassium hydroxide and dimethyl sulfoxide, is
      described. The reaction can be performed between a broad range of starting
      nucleophiles including phenol, alcohols, amines, nitrogen-containing five
      membered systems such as pyrazoles, imidazoles, and indoles, and amides with
      haloarenes, iodide and bromide derivatives giving the best results, the possible
      pathway involving the in situ generation of the corresponding benzyne
      intermediate. When the reaction was performed with 2-iodoaniline and either
      carboxamides or isothiocyanato derivatives, the corresponding benzoazole
      derivatives were obtained.

PMID- 21175157
TI  - Ligand-assisted rate acceleration in lanthanum(III) isopropoxide catalyzed
      transesterification of carboxylic esters.
AB  - The transesterification of an equimolar mixture of carboxylic esters and primary
      (1 degrees ), secondary (2 degrees ), and tertiary (3 degrees ) alcohols in
      hydrocarbon solvents was promoted with high efficiency by a lanthanum(III)
      complex, which was prepared in situ from lanthanum(III) isopropoxide (1 mol %)
      and 2-(2-methoxyethoxy)ethanol (2 mol %). The present La(III) catalyst was highly
      effective for the chemoselective transesterification in the presence of
      competitive 1 degrees - and 2 degrees -amines. Remarkably, esters were obtained
      in good to excellent yields as colorless materials without an inconvenient workup
      procedure.

PMID- 21175158
TI  - Fluorescent signaling of oxone by desulfurization of thioamide.
AB  - The chemosignaling of the oxidant Oxone by selective desulfurization of a
      thioamide was investigated. Pyrene-thioamide was efficiently converted to its
      amide analogue by reaction with Oxone, resulting in a pronounced fluorescent turn
      on type signaling. Selective signaling of Oxone in aqueous solution was possible
      in the presence of representative alkali and alkaline earth metal ions, as well
      as common anions.

PMID- 21175159
TI  - Lanthanum(III) isopropoxide catalyzed chemoselective transesterification of
      dimethyl carbonate and methyl carbamates.
AB  - A practical transesterification of less reactive dimethyl carbonate and much less
      reactive methyl carbamates with primary (1 degrees ), secondary (2 degrees ), and
      tertiary (3 degrees ) alcohols was established with the use of a lanthanum(III)
      complex, which was prepared in situ from lanthanum(III) isopropoxide (3 mol %)
      and 2-(2-methoxyethoxy)ethanol (6 mol %). In particular, corresponding carbonates
      and carbamates obtained were of synthetic utility from the viewpoint of the
      selective protection and/or deprotection of 1 degrees -, 2 degrees -, and 3
      degrees -alcohols.

PMID- 21175156
TI  - Pyrrolinone-based peptidomimetics. "Let the enzyme or receptor be the judge".
AB  - Peptides and proteins, evolved by nature to perform vital biological functions,
      would constitute ideal candidates for therapeutic intervention were it not for
      their generally poor pharmacokinetic profiles. Nonpeptide peptidomimetics have
      thus been pursued because they might overcome these limitations while maintaining
      both the potency and selectivity of the parent peptide or protein. Since the late
      1980s, we have sought to design, synthesize, and evaluate a novel,
      proteolytically stable nonpeptide peptidomimetic scaffold consisting of a
      repeating structural unit amenable to iterative construction; a primary concern
      is maintaining both the appropriate peptide-like side-chains and requisite
      hydrogen bonding. In this Account, we detail how efforts in the Smith-Hirschmann
      laboratories culminated in the identification of the 3,5-linked polypyrrolinone
      scaffold. We developed effective synthetic protocols, both in solution and on
      solid supports, for iterative construction of diverse polypyrrolinones that
      present functionalized peptide-like side-chains. As a result of the rigid nature
      of the pyrrolinone scaffold, control over the backbone conformation could be
      exerted by modulation of the stereogenicity of the constituent monomers and the
      network of intramolecular hydrogen bonding. The extended conformation of the
      homochiral 3,5-linked polypyrrolinone scaffold proved to be an excellent mimic
      for beta-strands and beta-sheets. Application to enzyme inhibitor design and
      synthesis led not only to modest inhibitors of the aspartic acid protease renin
      and the matrix metalloprotease class of enzymes, but importantly to bioavailable
      HIV-1 protease inhibitors with subnanomolar binding constants. The design and
      synthesis of a competent peptide-pyrrolinone hybrid ligand for the class II major
      histocompatibility complex (MHC) antigen protein HLA-DR1 further demonstrated the
      utility of the 3,5-polypyrrolinone motif as a mimic for the extended polyproline
      type II peptide backbone. Equally important, we sought to define, by synthesis,
      the additional conformational space accessible to the polypyrrolinone structural
      motif, with the ultimate goal of accessing pyrrolinone-based turn and helix
      mimetics. Toward this end, a mono-N-methylated bispyrrolinone was found to adopt
      an extended helical array in the solid state. Subsequent synthesis of d,l
      alternating (heterochiral) tetrapyrrolinones both validated the expected turn
      conformations in solution and led to a functionally active mimetic of a peptidal
      beta-turn (similar to somatostatin). Finally, the design, synthesis, and
      structural evaluation of both acyclic and cyclic heterochiral (that is, d,l
      alternating) hexapyrrolinones yielded nanotube-like assemblies in the solid
      state. Taken together, these results illustrate the remarkable potential of the
      3,5-linked polypyrrolinone scaffold as beta-strand, beta-sheet, beta-turn, and
      potentially helical peptidomimetics.

PMID- 21175160
TI  - Periodic titania nanostructures using block copolymer templates.
AB  - The deposition of periodic titania nanostructures, templated by a polystyrene
      block-poly(4-vinylpyridine) (PS-b-P4VP) block copolymer, is reported. When cast
      as a thin film (30-50 nm thick), the PS-b-P4VP forms a morphology that consists
      of P4VP cylinders that are orientated perpendicular to the substrate. The P4VP
      phase was lightly cross-linked by exposing the film to diiodobutane. When the
      block copolymer film was exposed to the sol-gel titania precursor, titanium(IV)
      bis(ammonium lactate) dihydroxide (TALH), titania was formed in the P4VP phase.
      The resulting titania structures were identical in size to the P4VP cylinders and
      only formed (under the deposition conditions used in this study) when the block
      copolymer film was present on the substrate, thus providing evidence that the
      block copolymer indeed acts as a template. The process works for both silicon and
      indium tin oxide substrates.

PMID- 21175161
TI  - Sensitizing the sensitizer: the synthesis and photophysical study of bodipy
      Pt(II)(diimine)(dithiolate) conjugates.
AB  - The dyads 3, 4, and 6, combining the Bodipy chromophore with a Pt(bpy)(bdt) (bpy
      = 2,2'-bipyridine, bdt = 1,2-benzenedithiolate, 3 and 6) or a Pt(bpy)(mnt) (mnt =
      maleonitriledithiolate, 4) moiety, have been synthesized and studied by UV-vis
      steady-state absorption, transient absorption, and emission spectroscopies and
      cyclic voltammetry. Comparison of the absorption spectra and cyclic voltammograms
      of dyads 3, 4, and 6 and those of their model compounds 1a, 2, 5, and 7 shows
      that the spectroscopic and electrochemical properties of the dyads are
      essentially the sum of their constituent chromophores, indicating negligible
      interaction of the constituent chromophores in the ground state. However,
      emission studies on 3 and 6 show a complete absence of both Bodipy-based
      fluorescence and the characteristic luminescence of the Pt(bpy)(bdt) unit. Dyad 4
      shows a weak Pt(mnt)-based emission. Transient absorption studies show that
      excitation of the dyads into the Bodipy-based (1)pipi* excited state is followed
      by singlet energy transfer (SEnT) to the Pt(dithiolate)-based (1)MMLL'CT (mixed
      metal-ligand to ligand charge transfer) excited state (tau(SEnT)(3) = 0.6 ps,
      tau(SEnT)(4) = 0.5 ps, and tau(SEnT)(6) = 1.6 ps), which undergoes rapid
      intersystem crossing to the (3)MMLL'CT state due to the heavy Pt(II) ion. The
      (3)MMLL'CT state is then depopulated by triplet energy transfer (TEnT) to the low
      lying Bodipy-based (3)pipi* excited state (tau(SEnT)(3) = 8.2 ps, tau(SEnT)(4) =
      5 ps, and tau(SEnT)(6) = 160 ps). The transition assignments are supported by TD
      DFT calculations. Both energy-transfer processes are shown to proceed via a
      Dexter electron exchange mechanism. The much longer time constants for dyad 6
      relative to 3 are attributed to the significantly poorer coupling and resonance
      of charge-separated species that are intermediates in the electron exchange
      process.

PMID- 21175163
TI  - Radical dependence of the yields of methacrolein and methyl vinyl ketone from the
      OH-initiated oxidation of isoprene under NO(x)-free conditions.
AB  - Formation yields of methacrolein (MAC), methyl vinyl ketone (MVK), and 3-methyl
      furan (3MF) from the hydroxyl radical (OH) initiated oxidation of isoprene were
      investigated under NO(x)-free conditions (NO(x) = NO + NO(2)) at 50  degrees C
      and 1 atm in a quartz reaction chamber coupled to a mass spectrometer. Yields of
      the primary products were measured at various OH and hydroperoxy (HO(2)) radical
      concentrations and were found to decrease as the HO(2)-to-isoprene-based peroxy
      radical (ISORO(2)) concentration ratio increases. This is likely the result of a
      competition between ISORO(2) self- and cross-reactions that lead to the formation
      of the primary products, with reactions between these peroxy radicals and HO(2)
      which can lead to the formation of peroxides. Under conditions with
      HO(2)/ISORO(2) ratios close to 0.1, yields of MVK (15.5% +/- 1.4%) and MAC (13.0%
      +/- 1.2%) were higher than the yields of MVK (8.9% +/- 0.9%) and MAC (10.9% +/-
      1.1%) measured under conditions with HO(2)/ISORO(2) ratios close to 1. This
      radical dependence of the yields was reproduced reasonably well by an explicit
      model of isoprene oxidation, suggesting that the model is able to reproduce the
      observed products yields under a realistic range of atmospheric HO(2)/ISORO(2)
      ratios.

PMID- 21175162
TI  - Synthesis and antiprotozoal activity of N-alkoxy analogues of the trypanocidal
      lead compound 4,4'-bis(imidazolinylamino)diphenylamine with improved human blood
      brain barrier permeability.
AB  - To improve the blood-brain barrier permeability of the trypanocidal lead compound
      4,4'-bis(imidazolinylamino)diphenylamine (1), five N-alkoxy analogues were
      synthesized from bis(4-isothiocyanatophenyl)amine and N-alkoxy-N-(2-aminoethyl)-2
      nitrobenzenesulfonamides following successive chemical reactions in just one
      reactor ("one-pot procedure"). This involved: (a) formation of a thiourea
      intermediate, (b) removal of the amine protecting groups, and (c) intramolecular
      cyclization. The blood-brain barrier permeability of the compounds determined in
      vitro by transport assays through the hCMEC/D3 human cell line, a well-known and
      characterized human cellular blood-brain barrier model, showed that the N-hydroxy
      analogue 16 had enhanced blood-brain barrier permeability compared with the
      unsubstituted lead compound. Moreover, this compound displayed low micromolar
      IC(50) against Trypanosoma brucei rhodesiense and Plasmodium falciparum and
      moderate activity by intraperitoneal administration in the STIB900 murine model
      of acute sleeping sickness.

PMID- 21175164
TI  - Experimental optimization of flow distributors for pressure-driven separations
      and reactions in flat-rectangular microchannels.
AB  - We report on the results of an experimental study established to optimize the
      design of microfabricated flow distributors for use in pressure-driven
      separations and reactions in flat-rectangular channels. For this purpose, the
      performance of a wide variety of possible flow distributor designs etched in
      glass/silicon wafers was compared, using CCD camera detection to study the shape
      and variance of the bands eluting from them. The best performance was obtained
      with radially interconnected distributors with a diverging inlet section and
      filled with diamond-shaped pillars, oriented perpendicular to the main flow
      direction and with a high transversal over axial aspect ratio. It was found that
      the best distributor designs start with a diverging section containing some 10-12
      subsequent rows of high aspect ratio pillars (with a transversal width making up
      10-15% of the final channel width) and with a divergence angle selected such that
      the sloped side-walls run parallel with the sides of the diamond-shaped pillars.
      After this zone, one or more regions with pillars with a smaller aspect ratio
      should be provided to increase the number of exit points. To prevent the
      formation of dead zones in these subsequent zones, so-called distributor wedges
      can be used to prevent the formation of any dead zones in the wake of the large
      aspect ratio pillars of the preceding section.

PMID- 21175165
TI  - Characterization of differences between blood sample matrices in untargeted
      metabolomics.
AB  - Large-scale proteomic and metabolomic technologies are increasingly gaining
      attention for their use in the diagnosis of human disease. In order to ensure the
      statistical power of relevant markers, such analyses must incorporate a large
      number of representative samples. While in a best-case scenario these samples are
      collected through a study design that is specifically tailored for the desired
      analysis, often studies must rely upon the analysis of large numbers of
      previously banked samples that may or may not have complete and accurate
      documentation of their associated collection and storage methods. In this study,
      several human blood matrices were analyzed and compared for the quality of
      metabolomic output. The sample types that were tested include plasma prepared
      with a variety of anticoagulants and serum collected by venipuncture and
      capillary blood collection protocols. Analysis with liquid chromatography-mass
      spectrometry (LC-MS) revealed only subtle differences between the various plasma
      preparation methods. Differences between the serum and plasma samples appear to
      be largely peptide/protein-based and are consistent with the biological
      distinction of the two matrices. Interestingly, the small molecule
      lysophosphatidylinositol was found to be in higher abundance in plasma, as a
      possible consequence of the effect of the intrinsic clotting cascade on adjacent
      metabolic pathways. Comparison of the small-molecule profiles of the capillary-
      and venipuncture-collected samples revealed 23 statistically significant compound
      differences between these sample types. Most of these features can be attributed
      to surfactants and detergents used to pretreat the skin in order to maintain the
      sterility of sample collection. However, several have identical mass and
      molecular formulas as endogenous human metabolites and could be erroneously
      attributed to actual metabolic perturbations. Understanding the extent of these
      matrix effects is important for control of systematic bias and ensuring the
      quality of metabolomic analysis.

PMID- 21175166
TI  - Graphene oxide sheet-mediated silver enhancement for application to
      electrochemical biosensors.
AB  - Functionalized graphene oxide (GO) sheets coupled with a signal amplification
      method based on the nanomaterial-promoted reduction of silver ions for the
      sensitive and selective detection of bacteria. This paper aims to develop an
      electrochemical route combined with GO sheet-mediated Ag enhancement for
      biological/chemical analyte detection. A linear relationship between the
      stripping response and the logarithm of the bacterial concentration was obtained
      using an electrochemical technique for concentrations ranging from 1.8 * 10(2) to
      1.8 * 10(8) cfu mL(-1), with a slope of 15.28 and a correlation coefficient of
      0.995. Dot blot assay was used as a conventional immunoassay method for
      comparison with the electrochemical method, as well as to observe the quality of
      the anti-sulfate-reducing bacteria (SRB) antibody (Ab) used in the immunosensor.
      The GO sheet-mediated silver enhancement holds great potential for the rapid
      analysis of protein, DNA, and pathogens.

PMID- 21175167
TI  - Pyrazine-2-amidoxime Ni(II) complexes: from ferromagnetic cluster to
      antiferromagnetic layer.
AB  - Tetranuclear [Ni(4)(Hpzaox)(2)(pzaox)(2)(py)(4)](ClO(4))(2).2py (1),
      [Ni(4)(Hpzaox)(2)(pzaox)(2)(py)(4)](NO(3))(2).4py (2), and two-dimensional (2D)
      [Ni(4)(Hpzaox)(2)(pzaox)(2)(H(2)O)(2)](NO(3))(2).2H(2)O (3) are prepared via the
      reaction of NiX(2).6H(2)O and pyrazine-2-amidoxime (H(2)pzaox). All compounds
      contain [Ni(4)(Hpzaox)(2)(pzaox)(2)](2+) fragments, which assemble to form a
      tetranuclear or polymeric network. Magnetic studies show that the tetranuclear
      compounds display usual ferromagnetic coupling via the oxime N-O bridges, and the
      2D compound displays unusual antiferromagnetic behavior.

PMID- 21175168
TI  - Macromolecular crowding tunes folding landscape of parallel alpha/beta protein,
      apoflavodoxin.
AB  - Proteins normally fold in crowded cellular environments. Here we use a set of
      Desulfovibrio desulfuricans apoflavodoxin variants to assess--with residue
      specific resolution--how apoflavodoxin's folding landscape is tuned by
      macromolecular crowding. We find that, under crowded conditions, initial
      topological frustration is reduced, subsequent folding requires less ordering in
      the transition state, and beta-strand 1 becomes more important in guiding the
      process. We propose that conditions more closely mimicking the cellular
      environment make the ensemble of unfolded conformations less expanded, resulting
      in a folding funnel that is smoother and narrower.

PMID- 21175169
TI  - Yttrium(III)-containing tungstoantimonate(III) stabilized by tetrahedral WO4(2-)
      capping unit, [{Y(alpha-SbW9O31(OH)2)(CH3COO)(H2O)}3(WO4)]17-.
AB  - The yttrium(III)-containing tungstoantimonate(III) [{Y(alpha
      SbW(9)O(31)(OH)(2))(CH(3)COO)(H(2)O)}(3)(WO(4))](17-) (1) has been synthesized in
      a simple one-pot reaction of Y(3+) ions with [alpha-SbW(9)O(33)](9-) and WO(4)(2
      ) in a 3:3:1 molar ratio in 1 M LiOAc/AcOH buffer at pH 5.3. Polyanion 1 is
      composed of three (alpha-SbW(9)O(33)) units linked by three Y(3+) ions and a
      capping, tetrahedral WO(4)(2-) capping unit, resulting in an assembly with C(3v)
      symmetry. The hydrated ammonium-sodium salt of 1 was investigated in the solid
      state by single-crystal XRD, FT-IR spectroscopy, thermogravimetric and elemental
      analyses, and in solution by multinuclear NMR spectroscopy.

PMID- 21175170
TI  - Quadrupole central transition 17O NMR spectroscopy of biological macromolecules
      in aqueous solution.
AB  - We demonstrate a general nuclear magnetic resonance (NMR) spectroscopic approach
      in obtaining high-resolution (17)O (spin-5/2) NMR spectra for biological
      macromolecules in aqueous solution. This approach, termed quadrupole central
      transition (QCT) NMR, is based on the multiexponential relaxation properties of
      half-integer quadrupolar nuclei in molecules undergoing slow isotropic tumbling
      motion. Under such a circumstance, Redfield's relaxation theory predicts that the
      central transition, m(I) = +1/2 <-> -1/2, can exhibit relatively long transverse
      relaxation time constants, thus giving rise to relatively narrow spectral lines.
      Using three robust protein-ligand complexes of size ranging from 65 to 240 kDa,
      we have obtained (17)O QCT NMR spectra with unprecedented resolution, allowing
      the chemical environment around the targeted oxygen atoms to be directly probed
      for the first time. The new QCT approach increases the size limit of molecular
      systems previously attainable by solution (17)O NMR by nearly 3 orders of
      magnitude (1000-fold). We have also shown that, when both quadrupole and
      shielding anisotropy interactions are operative, (17)O QCT NMR spectra display an
      analogous transverse relaxation optimized spectroscopy type behavior in that the
      condition for optimal resolution depends on the applied magnetic field. We
      conclude that, with the currently available moderate and ultrahigh magnetic
      fields (14 T and higher), this (17)O QCT NMR approach is applicable to a wide
      variety of biological macromolecules. The new (17)O NMR parameters so obtained
      for biological molecules are complementary to those obtained from (1)H, (13)C,
      and (15)N NMR studies.

PMID- 21175171
TI  - Silicon oxide: a non-innocent surface for molecular electronics and
      nanoelectronics studies.
AB  - Silicon oxide (SiO(x)) has been widely used in many electronic systems as a
      supportive and insulating medium. Here, we demonstrate various electrical
      phenomena such as resistive switching and related nonlinear conduction, current
      hysteresis, and negative differential resistance intrinsic to a thin layer of
      SiO(x). These behaviors can largely mimic numerous electrical phenomena observed
      in molecules and other nanomaterials, suggesting that substantial caution should
      be paid when studying conduction in electronic systems with SiO(x) as a
      component. The actual electrical phenomena can be the result of conduction from
      SiO(x) at a post soft-breakdown state and not the presumed molecular or
      nanomaterial component. These electrical properties and the underlying mechanisms
      are discussed in detail.

PMID- 21175172
TI  - Total synthesis of lamellarins D, H, and R and ningalin B.
AB  - A concise total synthesis of lamellarins D (7 steps), H (7 steps), and R (5
      steps) and ningalin B (5 steps) is achieved starting from the corresponding
      aldehydes and amines. The synthesis features three oxidative reactions as key
      steps in a biomimetic manner, involving an AgOAc-mediated oxidative coupling
      reaction to construct the pyrrole core, a Pb(OAc)(4)-induced oxidative
      cyclization to form the lactone, and Kita's oxidation reaction to form the
      pyrrole-arene C-C bond.

PMID- 21175173
TI  - Colloidal iron pyrite (FeS2) nanocrystal inks for thin-film photovoltaics.
AB  - Iron pyrite (FeS2) is a promising earth-abundant semiconductor for thin-film
      solar cells. In this work, phase-pure, single-crystalline, and well-dispersed
      colloidal FeS2 nanocrystals (NCs) were synthesized in high yield by a simple hot
      injection route in octadecylamine and then were subjected to partial ligand
      exchange with octadecylxanthate to yield stable pyrite NC inks. Polycrystalline
      pyrite thin films were fabricated by sintering layers of these NCs at 500-600 
      degrees C under a sulfur atmosphere.

PMID- 21175174
TI  - Original design of an oxygen-tolerant [NiFe] hydrogenase: major effect of a
      valine-to-cysteine mutation near the active site.
AB  - Hydrogenases are efficient biological catalysts of H(2) oxidation and production.
      Most of them are inhibited by O(2), and a prerequisite for their use in
      biotechnological applications under air is to improve their oxygen tolerance. We
      have previously shown that exchanging the residue at position 74 in the large
      subunit of the oxygen-sensitive [NiFe] hydrogenase from Desulfovibrio
      fructosovorans could impact the reaction of the enzyme with O(2) (Dementin, S.;
      J. Am. Chem. Soc. 2009, 131, 10156-10164; Liebgott, P. P.; Nat. Chem. Biol. 2010,
      6, 63-70). This residue, a valine in the wild-type enzyme, located at the
      bottleneck of the gas channel near the active site, has here been exchanged with
      a cysteine. A thorough characterization using a combination of kinetic,
      spectroscopic (EPR, FTIR), and electrochemical studies demonstrates that the V74C
      mutant has features of the naturally occurring oxygen-tolerant membrane-bound
      hydrogenases (MBH). The mutant is functional during several minutes under O(2),
      has impaired H(2)-production activity, and has a weaker affinity for CO than the
      WT. Upon exposure to O(2), it is converted into the more easily reactivatable
      inactive form, Ni-B, and this inactive state reactivates about 20 times faster
      than in the WT enzyme. Control experiments carried out with the V74S and V74N
      mutants indicate that protonation of the position 74 residue is not the reason
      the mutants reactivate faster than the WT enzyme. The electrochemical behavior of
      the V74C mutant toward O(2) is intermediate between that of the WT enzyme from D.
      fructosovorans and the oxygen-tolerant MBH from Aquifex aeolicus.

PMID- 21175175
TI  - Highly sensitive detection of exocytotic dopamine release using a gold
      nanoparticle-network microelectrode.
AB  - Here we report a new type of microelectrode sensor for single-cell exocytotic
      dopamine release. The new microsensor is built by forming a gold-nanoparticle
      (AuNP) network on a carbon fiber microelectrode. First a gold surface is obtained
      on a carbon fiber microdisk electrode by partially etching away the carbon
      followed by electrochemical deposition of gold into the pore. The gold surface is
      chemically functionalized with a sol-gel silicate network derived from (3
      mercaptopropyl)trimethoxysilane (MPTS). A AuNP network is formed by immobilizing
      Au nanoparticles onto the thiol groups in the sol-gel silicate network. The AuNP
      network microelectrode has been characterized by scanning electron microscopy
      (SEM) and steady-state voltammetry. The AuNP-network microelectrode has been used
      for amperometric detection of exocytotic dopamine secretion from individual
      pheochromocytoma (PC12) cells. The results show significant differences in the
      kinetic peak parameters including shorter rise time, decay time, and half-width
      as compared to a bare carbon fiber electrode equivalent. These results indicate
      AuNP-network microelectrodes possess an excellent sensing activity for single
      cell exocytotic catecholamine release, specifically dopamine. Moreover, key
      advantageous properties inherent to bare carbon fiber microelectrodes (i.e.,
      rigidity, flexibility, and small size) are maintained in addition to an observed
      prolonged shelf life stability and resistance to cellular debris fouling and
      dopamine polymerization.

PMID- 21175176
TI  - Vitamins E and C may increase collagen turnover by intramuscular fibroblasts.
      Potential for improved meat quality.
AB  - Vitamins influence collagen metabolism in animals grown for meat. This study
      investigated whether vitamins E and C regulate collagen turnover in muscle by the
      balance of effects on the synthesis of collagen and its degradation by secretion
      of matrix metalloproteinases (MMPs) by bovine intramuscular fibroblasts.
      Fibroblasts isolated from longissimus dorsi (LD) and semitendinosus (ST) muscle
      were treated with different concentrations of vitamins. Pro-MMP-2, MMP-2, and
      total soluble collagen (TSC) synthesis were determined. Vitamins E and C each
      preferentially increased (P < 0.05) MMP-2 in cells derived from LD relative to
      those derived from ST. Higher TSC values (P < 0.05) were found for ST cells than
      for LD cells. Both vitamins may increase collagen turnover exerted by
      intramuscular connective tissue fibroblasts. These results may have implications
      in vivo on animal production, as a high rate of collagen turnover may lead to
      increased collagen solubility in muscles, which can affect meat tenderness.

PMID- 21175177
TI  - Total synthesis of bryostatin 1.
AB  - Bryostatin 1 is a marine natural product that is a very promising lead compound
      because of the potent biological activity it displays against a variety of human
      disease states. We describe herein the first total synthesis of this agent. The
      synthetic route adopted is a highly convergent one in which the preformed,
      heavily functionalized pyran rings A and C are united by "pyran annulation", the
      TMSOTf-promoted reaction between a hydroxyallylsilane appended to the A-ring
      fragment and an aldehyde contained in the C-ring fragment, with concomitant
      formation of the B ring. Further elaborations of the resulting very highly
      functionalized intermediate include macrolactonization and selective cleavage of
      just one of five ester linkages present.

PMID- 21175178
TI  - Amplification of anti-diastereoselectivity via Curtin-Hammett effects in
      ruthenium-catalyzed hydrohydroxyalkylation of 1,1-disubstituted allenes:
      diastereoselective formation of all-carbon quaternary centers.
AB  - Under the conditions of ruthenium-catalyzed transfer hydrogenation, 1,1
      disubstituted allenes 1a-c and alcohols 2a-g engage in redox-triggered generation
      of allylruthenium-aldehyde pairs to form products of hydrohydroxyalkylation 3a-g,
      4a-g, and 5a-g with complete branched regioselectivity. By exploiting Curtin
      Hammett effects, good to excellent levels of anti-diastereoselectivity (4:1 to
      >20:1) are obtained. Thus, all carbon quaternary centers are formed in a
      diastereoselective fashion upon carbonyl addition from the alcohol oxidation
      level in the absence of premetalated nucleophiles or stoichiometric byproducts.
      Exposure of allene 1b to equimolar quantities of alcohol 2a and aldehyde 6b under
      standard reaction conditions delivers adducts 4a and 4b in a 1:1 ratio.
      Similarly, exposure of allene 1b to equimolar quantities of aldehyde 6a and
      alcohol 2b provides adducts 4a and 4b in an identical equimolar ratio. Exposure
      of allene 1b to d(2)-p-nitrobenzyl alcohol, deuterio-2a, under standard reaction
      conditions delivers the product of hydrohydroxyalkylation, deuterio-4a, which
      incorporates deuterium at the carbinol position (>95% (2)H) and the interior
      vinylic position (34% (2)H). Competition experiments involving exposure of allene
      1b to equimolar quantities of benzylic alcohols 2a and deuterio-2a reveal no
      significant kinetic effect. The collective data corroborate rapid, reversible
      alcohol dehydrogenation, allene hydrometalation, and (E)-, (Z)-isomerization of
      the transient allylruthenium in advance of turnover-limiting carbonyl addition.
      Notably, analogous allene-aldehyde reductive C-C couplings employing 2-propanol
      as the terminal reductant display poor levels of anti-diastereoselectivity,
      suggesting that carbonyl addition is not turnover-limiting in reactions conducted
      from the aldehyde oxidation level.

PMID- 21175179
TI  - Organic multiferroic tunnel junctions with ferroelectric poly(vinylidene
      fluoride) barriers.
AB  - Organic materials are promising for applications in spintronics due to their long
      spin-relaxation times in addition to their chemical flexibility and relatively
      low production costs. Most studies of organic materials for spintronics focus on
      nonpolar dielectrics or semiconductors, serving as passive elements in spin
      transport devices. Here, we demonstrate that employing organic ferroelectrics,
      such as poly(vinylidene fluoride) (PVDF), as barriers in magnetic tunnel
      junctions (MTJs) allows new functionality in controlling the tunneling spin
      polarization via the ferroelectric polarization of the barrier. Using first
      principles methods based on density functional theory we investigate the spin
      resolved conductance of Co/PVDF/Co and Co/PVDF/Fe/Co MTJs as model systems. We
      show that these tunnel junctions exhibit multiple resistance states associated
      with different magnetization configurations of the electrodes and ferroelectric
      polarization orientations of the barrier. Our results indicate that organic
      ferroelectrics may open a new and promising route in organic spintronics with
      implications for low-power electronics and nonvolatile data storage.

PMID- 21175180
TI  - Structures and dynamic behavior of large polyhedral coordination cages: an
      unusual cage-to-cage interconversion.
AB  - The bis-bidentate bridging ligand L {alpha,alpha'-bis[3-(2-pyridyl)pyrazol-1-yl]
      1,4-dimethylbenzene}, which contains two chelating pyrazolyl-pyridine units
      connected to a 1,4-phenylene spacer via flexible methylene units, reacts with
      transition metal dications to form a range of polyhedral coordination cages based
      on a 2M:3 L ratio in which a metal ion occupies each vertex of a polyhedron, a
      bridging ligand lies along every edge, and all metal ions are octahedrally
      coordinated. Whereas the Ni(II) complex [Ni(8)L(12)](BF(4))(12)(SiF(6))(2) is an
      octanuclear cubic cage of a type we have seen before, the Cu(II), Zn(II), and
      Cd(II) complexes form new structural types. [Cu(6)L(9)](BF(4))(12) is an unusual
      example of a trigonal prismatic cage, and both Zn(II) and Cd(II) form
      unprecedented hexadecanuclear cages [M(16)L(24)]X(32)(X = ClO(4) or BF(4)) whose
      core is a skewed tetracapped truncated tetrahedron. Both Cu(6)L(9) and M(16)L(24)
      cages are based on a cyclic helical M(3)L(3) subunit that can be considered as a
      triangular "panel", with the cages being constructed by interconnection of these
      (homochiral) panels with additional bridging ligands in different ways. Whereas
      [Cu(6)L(9)](BF(4))(12) is stable in solution (by electrospray mass spectrometry,
      ES-MS) and is rapidly formed by combination of Cu(BF(4))(2) and L in the correct
      proportions in solution, the hexadecanuclear cage [Cd(16)L(24)](BF(4))(32) formed
      on crystallization slowly rearranges in solution over a period of several weeks
      to the trigonal prism [Cd(6)L(9)](BF(4))(12), which was unequivocally identified
      on the basis of its (1)H NMR spectrum. Similarly, combination of Cd(BF(4))(2) and
      L in a 2:3 ratio generates a mixture whose main component is the trigonal prism
      [Cd(6)L(9)](BF(4))(12). Thus the hexanuclear trigonal prism is the thermodynamic
      product arising from combination of Cd(II) and L in a 2:3 ratio in solution, and
      arises from both assembly of metal and ligand (minutes) and rearrangement of the
      Cd(16) cage (weeks); the large cage [Cd(16)L(24)](BF(4))(32) is present as a
      minor component of a mixture of species in solution but crystallizes
      preferentially.

PMID- 21175181
TI  - Dynamic kinetic resolution of azlactones catalyzed by chiral Bronsted acids.
AB  - Chiral Bronsted acids have been shown for the first time to catalyze the dynamic
      kinetic resolution of azlactones. 3,3'-Bis-(9-anthryl)-BINOL phosphoric acid 3c
      is particularly effective in the case of 4-aryl-substituted substrates, producing
      85-92% ee's.

PMID- 21175183
TI  - A generalized ligand-exchange strategy enabling sequential surface
      functionalization of colloidal nanocrystals.
AB  - The ability to engineer surface properties of nanocrystals (NCs) is important for
      various applications, as many of the physical and chemical properties of
      nanoscale materials are strongly affected by the surface chemistry. Here, we
      report a facile ligand-exchange approach, which enables sequential surface
      functionalization and phase transfer of colloidal NCs while preserving the NC
      size and shape. Nitrosonium tetrafluoroborate (NOBF4) is used to replace the
      original organic ligands attached to the NC surface, stabilizing the NCs in
      various polar, hydrophilic media such as N,N-dimethylformamide for years, with no
      observed aggregation or precipitation. This approach is applicable to various NCs
      (metal oxides, metals, semiconductors, and dielectrics) of different sizes and
      shapes. The hydrophilic NCs obtained can subsequently be further functionalized
      using a variety of capping molecules, imparting different surface
      functionalization to NCs depending on the molecules employed. Our work provides a
      versatile ligand-exchange strategy for NC surface functionalization and
      represents an important step toward controllably engineering the surface
      properties of NCs.

PMID- 21175182
TI  - Fluorescent-responsive synthetic C1b domains of protein kinase Cdelta as
      reporters of specific high-affinity ligand binding.
AB  - Protein kinase C (PKC) is a critical cell signaling pathway involved in many
      disorders such as cancer and Alzheimer-type dementia. To date, evaluation of PKC
      ligand binding affinity has been performed by competitive studies against
      radiolabeled probes that are problematic for high-throughput screening. In the
      present study, we have developed a fluorescent-based binding assay system for
      identifying ligands that target the PKC ligand binding domain (C1 domain). An
      environmentally sensitive fluorescent dye (solvatochromic fluorophore), which has
      been used in multiple applications to assess protein-binding interactions, was
      inserted in proximity to the binding pocket of a novel PKCdelta C1b domain. These
      resultant fluorescent-labeled deltaC1b domain analogues underwent a significant
      change in fluorescent intensity upon ligand binding, and we further demonstrate
      that the fluorescent deltaC1b domain analogues can be used to evaluate ligand
      binding affinity.

PMID- 21175185
TI  - Surface patterning: more than just scratching the surface.

PMID- 21175184
TI  - Antioxidant activity and inhibition of lipid peroxidation in germinating seeds of
      transgenic soybean expressing OsHGGT.
AB  - Tocochromanols are potent lipid-soluble antioxidants and essential nutrients for
      human health. Genetic engineering techniques were used to develop soybeans with
      enhanced vitamin E levels, including tocotrienols, which are not found in
      soybean. The gene encoding rice homogentisate geranylgeranyl transferase (HGGT)
      was overexpressed in soybeans using seed-specific and constitutive promoters. The
      association between abundance of vitamin E isomers and antioxidant activity was
      investigated during seed germination. With the exception of beta-tocotrienol, all
      vitamin E isomers were detected in germinating seeds expressing OsHGGT. The
      antioxidant properties of germinating seed extracts were determined using 1,1
      diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzthiazoline-6
      sulfonic acid) (ABTS) radicals and lipid peroxidation (TBARS). Compared with
      intact wild-type seeds, transgenic seeds showed increases in radical scavenging
      of 5.4-17 and 23.2-35.3% in the DPPH and ABTS assays, respectively. Furthermore,
      the lipid peroxidation levels were 2.0-4.5-fold lower in germinating seeds from
      transgenic lines than in wild-type seeds. Therefore, it appears that the
      antioxidant potential of transgenic oil-producing plants such as soybean,
      sunflower, and corn may be enhanced by overexpressing OsHGGT during seed
      germination.

PMID- 21175186
TI  - Analysis of atomic scale chemical environments of boron in coal by 11B solid
      state NMR.
AB  - Atomic scale chemical environments of boron in coal has been studied by solid
      state NMR spectroscopy including magic angle spinning (MAS), satellite transition
      magic angle spinning (STMAS), and cross-polarization magic angle spinning
      (CPMAS). The (11)B NMR spectra can be briefly classified according to the degree
      of coalification. On the (11)B NMR spectra of lignite, bituminous, and sub
      bituminous coals (carbon content of 70-90mass%), three sites assigned to four
      coordinate boron ([4])B with small quadrupolar coupling constants (<=0.9 MHz) are
      observed. Two of the ([4])B sites in downfield are considered organoboron
      complexes with aromatic ligands, while the other in the most upper field is
      considered inorganic tetragonal boron (BO(4)). By contrast, on the (11)B NMR
      spectra of blind coal (carbon content >90mass%), the ([4])B which substitutes
      tetrahedral silicon of Illite is observed as a representative species. It has
      been considered that the organoboron is decomposed and released from the parent
      phase with the advance of coal maturation, and then the released boron reacts
      with the inorganic phase to substitute an element of inorganic minerals.
      Otherwise boron contained originally in inorganic minerals might remain preserved
      even under the high temperature condition that is generated during coalification.

PMID- 21175187
TI  - Rapid determination of lignin content of straw using fourier transform mid
      infrared spectroscopy.
AB  - To determine lignin content in triticale and wheat straws, calibration models
      were built using Fourier transform mid-infrared spectroscopy combined with
      partial least-squares regression. The best model for triticale and wheat straws
      was built using averaged spectra with raw spectrum in spectrum format and
      constant in path length as spectral pretreatments. The values of r(2), root-mean
      square error of prediction (RMSEP), and residual predictive deviation (RPD) for
      the triticale straw model were 0.935, 0.305, and 3.89, respectively. The r(2),
      RMSEP, and RPD values for the wheat straw model were 0.985, 0.163, and 8.50,
      respectively. Both models showed good predictive ability. A model built using
      both triticale and wheat straws indicated that the values of r(2), RMSEP, and RPD
      were 0.952, 0.27, and 4.63, respectively. This model also showed good predictive
      ability and could predict lignin contents in triticale and wheat straws with the
      same high accuracy.

PMID- 21175188
TI  - Proteomic analysis of up-accumulated proteins associated with fruit quality
      during autumn olive (Elaeagnus umbellata) fruit ripening.
AB  - Fruit ripening is a complex phenomenon that makes berries attractive and also
      determines their nutritional value. Autumn olive ( Elaeagnus umbellata Thunb.)
      fruit is a rich source of many human health-related nutrients. The changes in
      pericarp color are initiated at early developmental stages, coinciding with the
      fast increase in fruit size. Fruit quality traits with special emphasis on
      soluble sugars, organic acids, lycopene, and total protein contents were assayed
      during the fruit ripening. In the fully ripe fruit, glucose and fructose were the
      principal sugars, malic acid was the most abundant organic acid, and lycopene
      concentration was extremely high. A proteomic analysis was used to identify up
      accumulated proteins induced by the ripening. Among 63 up-accumulated protein
      spots, 43 were successfully identified by MALDI-TOF/TOF-MS. All 43 proteins were
      novel for autumn olive, and 8 were first reported in the fruit. Twenty-one
      proteins of known function were involved in sugar metabolism, citric acid cycle,
      isoprenoid metabolism, fatty acid synthesis, and protein hydrolysis. The possible
      roles of these 21 accumulated proteins in autumn olive fruit quality are
      discussed.

PMID- 21175189
TI  - Hydrocolloid interaction with water, protein, and starch in wheat dough.
AB  - Interaction of hydrocolloids (xanthan gum, locust bean gum, guar gum, and high
      methoxyl pectin) with macrocomponents of dough (water, starch, and protein) was
      evaluated by different techniques. (1)H spin-spin NMR relaxation assays were
      applied to study the mobility of the gluten-hydrocolloid-water matrix, and the
      amount of freezable water was determined by differential scanning calorimetry
      (DSC). Starch gelatinization parameters (T, enthalpy) were also analyzed by DSC.
      The influence of additives on the protein matrix was studied by Fourier transform
      (FT) Raman assays; analysis of the extracted gliadins and glutenins was performed
      by electrophoresis (SDS-PAGE). A significantly higher molecular mobility was
      found in matrices containing xanthan gum, whereas pectin led to the lowest
      molecular mobility. Freezable water showed a trend of increasing in the presence
      of hydrocolloids, particularly under conditions of water restriction. Starch
      gelatinization final temperature was decreased when hydrocolloids were added in
      the presence of enough water. In general, FT-Raman and SDS-PAGE indicated that
      hydrocolloid addition promoted a more disordered and labile network, particularly
      in the case of pectin addition. On the other hand, results obtained for dough
      with guar gum would indicate a good compatibility between this hydrocolloid and
      the gluten network.

PMID- 21175190
TI  - High level of mislabeling in Spanish and Greek hake markets suggests the
      fraudulent introduction of African species.
AB  - DNA analysis of hake products commercialized in southern European (Spanish and
      Greek) market chains have demonstrated more than 30% mislabeling, on the basis of
      species substitution. Tails and fillets were more mislabeled than other products,
      such as slices and whole pieces. African species were substitute species for
      products labeled as American and European species, and we suggest it is a case of
      deliberate economically profitable mislabeling because real market prices of
      European and American hake products are higher than those of African in Spanish
      market chains. The presented results suggest fraud detection that disadvantages
      African producers. Government-mandated genetic surveys of commercial hakes and
      the use of subsequent statements of fair trade on labels of seafood products
      could help to reduce fraud levels in a global market of increasingly conscious
      consumers sensitive to ethical issues.

PMID- 21175191
TI  - Synthesis, crystal structures, insecticidal activities, and structure--activity
      relationships of novel N'-tert-Butyl-N'-substituted-benzoyl-N
      [di(octa)hydro]benzofuran{(2,3-dihydro)benzo[1,3]([1,4])dioxine}carbohydrazide
      derivatives.
AB  - Several series of novel N'-tert-butyl-N'-substituted-benzoyl-N
      [di(octa)hydro]benzofuran{(2,3-dihydro)benzo[1,3]([1,4])dioxine}carbohydrazide
      derivatives Ia, Ib, IIa-IIg, IIIa, IIIb, and Va-Vc were designed and synthesized.
      Their structures were confirmed by (1)H NMR spectra, HRMS, and X-ray single
      crystal structures. The larvicidal activities against oriental armyworm, beet
      armyworm, diamond-back moth, and corn borer of these compounds were evaluated and
      contrasted with those of RH-2485, JS-118, and ANS-118. The larvicidal activities
      against oriental armyworm indicate that monosubstituent or multisubstituents and
      the substituting group position cannot promote increasing activities and that the
      cycle region in the general structure of IIa-IIg is much more sensitive to
      activity than that in the general structure of Ia and Ib. The space volume of the
      A ring in the structure of Va cannot be too large; if it is, the activity will be
      decreased significantly. Stomach toxicities against beet armyworm, diamond-back
      moth, and corn borer of compounds Ia, Ib and IIg indicate that benzoheterocyclic
      analogues of N-tert-butyl-N,N'-diacylhydrazines show significant selectivities to
      different lepidopterous pests.

PMID- 21175192
TI  - Topological study of the late steps of the artemisinin decomposition process:
      modeling the outcome of the experimentally obtained products.
AB  - By using 6,7,8-trioxabicyclo[3.2.2]nonane as the artemisinin model and dihydrated
      Fe(OH)(2) as the heme model, we report a theoretical study of the late steps of
      the artemisinin decomposition process. The study offers two viewpoints: first,
      the energetic and geometric parameters are obtained and analyzed, and hence,
      different reaction paths have been studied. The second point of view uses the
      electron localization function (ELF) and the atoms in molecules (AIM)
      methodology, to conduct a complete topological study of such steps. The MO
      analysis together with the spin density description has also been used. The
      obtained results agree nicely with the experimental data, and a new mechanistic
      proposal that explains the experimentally determined outcome of deoxiartemisinin
      has been postulated.

PMID- 21175193
TI  - Purple rice extract and anthocyanidins of the constituents protect against light
      induced retinal damage in vitro and in vivo.
AB  - This study evaluated the protective effects of purple rice ( Oryza sativa L.)
      bran extract (PRE) and its major anthocyanidins (cyanidin and peonidin) against
      light-induced retinal damage. In an in vitro experiment, cultured murine
      photoreceptor cells (661W) were damaged by a 24 h exposure to light. Viability of
      661W after light treatment, assessed by the tetrazolium salt (WST-8) assay and
      Hoechst 33342 nuclear staining, was improved by the addition of PRE, cyanidin,
      and peonidin. Intracellular radical activation in 661W, evaluated using the
      reactive oxygen species (ROS) sensitive probe 5-(and 6)-chloromethyl-2,7
      dichlorodihydrofluorescein diacetate acetyl ester (CM-H(2)DCFDA), was reduced by
      PRE and its anthocyanidins. Electron spin resonance (ESR) measurements showed
      that PRE, peonidin, and cyanidin all exhibited radical scavenging activities
      against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, superoxide anion radical
      ((*)O(2)(-)), and hydroxyl radical ((*)OH). In an in vivo mouse experiment,
      intravitreous injection of PRE significantly suppressed photoreceptor
      degeneration induced by exposure to light as revealed by histological analysis
      using hematoxylin-eosin staining. These findings suggest that PRE and its
      anthocyanidins possess protective effects with antioxidation mechanism in both in
      vitro and in vivo models of retinal diseases.

PMID- 21175194
TI  - Direct, one-pot reductive alkylation of anilines with functionalized acetals
      mediated by triethylsilane and TFA. Straightforward route for unsymmetrically
      substituted ethylenediamine.
AB  - A new, robust, and reliable method has been developed for the selective reductive
      N-alkylation of primary and secondary aromatic amines with some functionalized
      acetals using TFA/Et(3)SiH as a reagent combination. A variety of unsymmetrically
      substituted ethylenediamines can be synthesized in a one-pot procedure in
      excellent yields at room temperature. This new procedure offers significant
      advantages over previous synthetic approaches, including brevity, mild reaction
      conditions, excellent yields, and high functional group tolerance.

PMID- 21175195
TI  - Reaction pathway and free energy profile for butyrylcholinesterase-catalyzed
      hydrolysis of acetylcholine.
AB  - A catalytic mechanism for the butyrylcholinesterase (BChE)-catalyzed hydrolysis
      of acetylcholine (ACh) has been studied by performing pseudobond first-principles
      quantum mechanical/molecular mechanical-free energy calculations on both
      acylation and deacylation of BChE. It has been shown that the acylation with ACh
      includes two reaction steps, including nucleophilic attack on the carbonyl carbon
      of ACh and dissociation of choline ester. The deacylation stage includes
      nucleophilic attack of a water molecule on the carboxyl carbon of the substrate
      and dissociation between the carboxyl carbon of the substrate and the hydroxyl
      oxygen of the Ser198 side chain. Notably, despite the fact that
      acetylcholinesterase (AChE) and BChE are very similar enzymes, the acylation of
      BChE with ACh is rate-determining, which is remarkably different from the AChE
      catalyzed hydrolysis of ACh, in which the deacylation is rate-determining. The
      computational prediction is consistent with available experimental kinetic data.
      The overall free energy barrier calculated for BChE-catalyzed hydrolysis of ACh
      is 13.8 kcal/mol, which is in good agreement with the experimentally derived
      activation free energy of 13.3 kcal/mol.

PMID- 21175196
TI  - Analysis of differential proteomes of induced pluripotent stem cells by protein
      based reprogramming of fibroblasts.
AB  - The recent generation of induced pluripotent stem (iPS) cells represents a novel
      opportunity to complement embryonic stem (ES) cell-based approaches. iPS cells
      can be generated by viral transduction of specific transcription factors, but
      there is a potential risk of tumorigenicity by random retroviral integration. We
      have generated novel iPS (sFB-protein-iPS) cells from murine dermal fibroblasts
      (FVB-sFB) that have ES cell characteristics, using ES cell-derived cell extracts
      instead of performing viral transduction. Notably, only cell extracts from an ES
      cell line (C57-mES) on the C57/BL6 background generated iPS cells in our protocol
      not an ES cell line (E14-mES) on the 129 background. Hypothesizing that
      determining the differences in these 2 mES cell lines will provide vital insight
      into the reprogramming machinery, we performed proteomic and global gene
      expression analysis by iTRAQ and mRNA microarray, respectively. We observed that
      pluripotent ES cells and ES cell extract-derived iPS cells had differential
      proteomes and global gene expression patterns. Notably, reprogramming-competent
      C57-mES cells highly expressed proteins that regulate protein synthesis and
      metabolism, compared with reprogramming-incompetent 129-mES cells, suggesting
      that there is a threshold that protein synthetic machinery must exceed to
      initiate reprogramming.

PMID- 21175197
TI  - Role for a conserved structural motif in assembly of a class I aminoacyl-tRNA
      synthetase active site.
AB  - The catalytic domains of class I aminoacyl-tRNA synthetases are built around a
      conserved Rossmann nucleotide binding fold, with additional polypeptide domains
      responsible for tRNA binding or hydrolytic editing of misacylated substrates.
      Structural comparisons identified a conserved motif bridging the catalytic and
      anticodon binding domains of class Ia and Ib enzymes. This stem contact fold
      (SCF) has been proposed to globally orient each enzyme's cognate tRNA by
      interacting with the inner corner of the L-shaped tRNA. Despite the structural
      similarity of the SCF among class Ia/Ib enzymes, the sequence conservation is
      low. We replaced amino acids of the MetRS SCF with portions of the structurally
      similar glutaminyl-tRNA synthetase (GlnRS) motif or with alanine residues.
      Chimeric variants retained significant tRNA methionylation activity, indicating
      that structural integrity of the helix-turn-strand-helix motif contributes more
      to tRNA aminoacylation than does amino acid identity. In contrast, chimeras were
      significantly reduced in methionyl adenylate synthesis, suggesting a role for the
      SCF in formation of a structured active site domain. A highly conserved aspartic
      acid within the MetRS SCF is proposed to make an electrostatic interaction with
      an active site lysine; these residues were replaced with alanines or conservative
      substitutions. Both methionyl adenylate formation and methionine transfer were
      impaired, and activity was not significantly recovered by making the compensatory
      double substitution.

PMID- 21175198
TI  - Xlink-identifier: an automated data analysis platform for confident
      identifications of chemically cross-linked peptides using tandem mass
      spectrometry.
AB  - Chemical cross-linking combined with mass spectrometry provides a powerful method
      for identifying protein-protein interactions and probing the structure of protein
      complexes. A number of strategies have been reported that take advantage of the
      high sensitivity and high resolution of modern mass spectrometers. Approaches
      typically include synthesis of novel cross-linking compounds, and/or isotopic
      labeling of the cross-linking reagent and/or protein, and label-free methods. We
      report Xlink-Identifier, a comprehensive data analysis platform that has been
      developed to support label-free analyses. It can identify interpeptide,
      intrapeptide, and deadend cross-links as well as underivatized peptides. The
      software streamlines data preprocessing, peptide scoring, and visualization and
      provides an overall data analysis strategy for studying protein-protein
      interactions and protein structure using mass spectrometry. The software has been
      evaluated using a custom synthesized cross-linking reagent that features an
      enrichment tag. Xlink-Identifier offers the potential to perform large-scale
      identifications of protein-protein interactions using tandem mass spectrometry.

PMID- 21175199
TI  - Investigation of the heating rate dependency associated with the loss of
      crystalline structure in sucrose, glucose, and fructose using a thermal analysis
      approach (part I).
AB  - Thermodynamic melting occurs at a single, time-independent temperature with a
      constant enthalpy value. However, substantial variation in the melting parameters
      (T(m onset), T(m peak), and DeltaH) for sucrose, glucose, and fructose has been
      reported in the literature. Although a number of explanations have been put
      forth, they do not completely account for the observed variation. Thus, this
      research was performed to elucidate the fundamental mechanism underlying the loss
      of crystalline structure in the sugars using both thermal (Part I) and chemical
      (Part II) analysis approaches. A strong heating rate dependency observed in the
      melting parameters for the sugars implies the occurrence of a kinetic process
      during the loss of crystalline structure. The difference in heat capacity and
      modulated heat flow amplitude in the stepwise quasi-isothermal modulated
      differential scanning calorimetry experiments for the sugars compared to indium
      and mannitol (thermodynamic melting comparison materials) strongly suggests
      thermal decomposition as the kinetic process responsible for the loss of
      crystalline structure, which is the critical difference between our conclusion
      and others. We propose the term "apparent melting" to distinguish the loss of
      crystalline structure due to a kinetic process, such as thermal decomposition,
      from thermodynamic melting.

PMID- 21175200
TI  - Investigation of thermal decomposition as the kinetic process that causes the
      loss of crystalline structure in sucrose using a chemical analysis approach (part
      II).
AB  - High performance liquid chromatography (HPLC) on a calcium form cation exchange
      column with refractive index and photodiode array detection was used to
      investigate thermal decomposition as the cause of the loss of crystalline
      structure in sucrose. Crystalline sucrose structure was removed using a standard
      differential scanning calorimetry (SDSC) method (fast heating method) and a quasi
      isothermal modulated differential scanning calorimetry (MDSC) method (slow
      heating method). In the fast heating method, initial decomposition components,
      glucose (0.365%) and 5-HMF (0.003%), were found in the sucrose sample coincident
      with the onset temperature of the first endothermic peak. In the slow heating
      method, glucose (0.411%) and 5-HMF (0.003%) were found in the sucrose sample
      coincident with the holding time (50 min) at which the reversing heat capacity
      began to increase. In both methods, even before the crystalline structure in
      sucrose was completely removed, unidentified thermal decomposition components
      were formed. These results prove not only that the loss of crystalline structure
      in sucrose is caused by thermal decomposition, but also that it is achieved via a
      time-temperature combination process. This knowledge is important for quality
      assurance purposes and for developing new sugar based food and pharmaceutical
      products. In addition, this research provides new insights into the
      caramelization process, showing that caramelization can occur under low
      temperature (significantly below the literature reported melting temperature),
      albeit longer time, conditions.

PMID- 21175201
TI  - Dosed without prescription: a framework for preventing pharmaceutical
      contamination of our nation's drinking water.

PMID- 21175202
TI  - Proteome analysis reveals a large merozoite surface protein-1 associated complex
      on the Plasmodium falciparum merozoite surface.
AB  - Plasmodium merozoite surface protein-1 (MSP-1) is an essential antigen for the
      merozoite invasion of erythrocytes. A key challenge to the development of an
      effective malaria vaccine that can block the erythrocyte invasion is to establish
      the molecular interaction(s) among the parasite surface proteins as well as with
      the host cell encoded receptors. In the present study, we applied molecular
      interactions and proteome approaches to identify PfMSP-1 associated complex on
      the merozoite surface. Proteomic analysis identified a major malaria surface
      protein, PfRhopH3 interacting with PfMSP-1(42). Pull-down experiments with
      merozoite lysate using anti-PfMSP-1 or anti-PfRhopH3 antibodies showed 16 bands
      that when identified by tandem mass spectrometry corresponded to11 parasite
      proteins: PfMSP-3, PfMSP-6, PfMSP-7, PfMSP-9, PfRhopH3, PfRhopH1, PfRAP-1, PfRAP
      2, and two RAP domain containing proteins. This MSP-1 associated complex was
      specifically seen at schizont/merozoite stages but not the next ring stage. We
      could also identify many of these proteins in culture supernatant, suggesting the
      shedding of the complex. Interestingly, the PfRhopH3 protein also showed binding
      to the human erythrocyte and anti-PfRhopH3 antibodies blocked the erythrocyte
      invasion of the merozoites. These results have potential implications in the
      development of PfMSP-1 based blood stage malaria vaccine.

PMID- 21175204
TI  - Solvent effects on the electronic transitions of p-nitroaniline: a QM/EFP study.
AB  - Solvatochromic shifts of the electronic states of a chromophore can be used as a
      measure of solute-solvent interactions. The shifts of the electronic states of a
      model organic chromophore, p-nitroaniline (pNA), embedded in solvents with
      different polarities (water, 1,4-dioxane, and cyclohexane) are studied using a
      hybrid quantum mechanics/molecular-mechanics-type technique in which the
      chromophore is described by the configuration interaction singles with
      perturbative doubles (CIS(D)) method while the solvent is treated by the
      effective fragment potential (EFP) method. This newly developed CIS(D)/EFP scheme
      includes the quantum-mechanical coupling of the Coulomb and polarization terms;
      however, short-range dispersion and exchange-repulsion terms of EFP are not
      included in the quantum Hamiltonian. The CIS(D)/EFP model is benchmarked against
      the more accurate equation of motion coupled cluster with singles and doubles
      (EOM-CCSD)/EFP method on a set of small pNA-water clusters. CIS(D)/EFP accurately
      predicts the red solvatochromic shift of the charge-transfer pi -> pi* state of
      pNA in polar water. The shift is underestimated in less polar dioxane and
      cyclohexane probably because of the omission of the explicit quantum-mechanical
      treatment of the short-range terms. Different solvation of singlet and triplet
      states of pNA results in different probabilities of intersystem crossing (ISC)
      and internal conversion (IC) pathways of energy relaxation in solvents of
      different polarity. Computed singlet-triplet splittings in water and dioxane
      qualitatively explain the active ISC channel in dioxane and predict almost no
      conversion to the triplet manifold in water, in agreement with experimental
      findings.

PMID- 21175203
TI  - Biosynthesis of the allylmalonyl-CoA extender unit for the FK506 polyketide
      synthase proceeds through a dedicated polyketide synthase and facilitates the
      mutasynthesis of analogues.
AB  - The allyl moiety of the immunosuppressive agent FK506 is structurally unique
      among polyketides and critical for its potent biological activity. Here, we
      detail the biosynthetic pathway to allylmalonyl-coenzyme A (CoA), from which the
      FK506 allyl group is derived, based on a comprehensive chemical, biochemical, and
      genetic interrogation of three FK506 gene clusters. A discrete polyketide
      synthase (PKS) with noncanonical domain architecture presumably in coordination
      with the fatty acid synthase pathway of the host catalyzes a multistep enzymatic
      reaction to allylmalonyl-CoA via trans-2-pentenyl-acyl carrier protein.
      Characterization of this discrete pathway facilitated the engineered biosynthesis
      of novel allyl group-modified FK506 analogues, 36-fluoro-FK520 and 36-methyl
      FK506, the latter of which exhibits improved neurite outgrowth activity. This
      unique feature of FK506 biosynthesis, in which a dedicated PKS provides an
      atypical extender unit for the main modular PKS, illuminates a new strategy for
      the combinatorial biosynthesis of designer macrolide scaffolds as well as FK506
      analogues.

PMID- 21175205
TI  - Dynamical signature of abasic damage in DNA.
AB  - Time-dependent Stokes shift (TDSS) responses in proteins and DNA exhibit a broad
      range of long time scales (>10 ps) that are not present in bulk aqueous solution.
      The physical interpretation of the long TDSS time scales in biomolecular systems
      is a matter of considerable debate because of the many different components
      present in the sample (water, biomolecule, counterions), which have highly
      correlated motions and intrinsically different abilities to adapt to local
      perturbations. Here we use molecular dynamics (MD) simulations to show that the
      surprisingly slow (~10 ns) TDSS response of coumarin 102 (C102), a base pair
      replacement, reflects a distinct dynamical signature for DNA damage. When the
      C102 molecule is covalently incorporated into DNA, an abasic site is created on
      the strand opposite the C102 probe. The abasic sugar exhibits a reversible
      interchange between intra- and extrahelical conformations that are kinetically
      stable on a nanosecond time scale. This conformational change, only possible in
      damaged DNA, was found to be responsible for the long time scales in the measured
      TDSS response. For the first time, a TDSS measurement has been attributed to a
      specific biomolecular motion. This finding directly contradicts the prevailing
      notion that the TDSS response in biomolecular contexts is dominated by hydration
      dynamics. It also suggests that TDSS experiments can be used to study ultrafast
      biomolecular dynamics that are inaccessible to other techniques.

PMID- 21175206
TI  - Border reactivity of polycyclic aromatic hydrocarbons and soot platelets toward
      ozone. A theoretical study.
AB  - PAH-based models, with an even or odd number of unsaturated carbon atoms and pi
      electrons (even and odd PAHs for short), are selected to investigate, by
      molecular and periodic methods, their electron distribution and border reactivity
      toward ozone, and also to represent local features and edge reactivity of even or
      odd soot platelets. These results will contrast those previously collected for
      the internal positions of similar even (J. Phys. Chem. A 2005, 109, 10929.) or
      odd systems (J. Phys. Chem. A 2008, 112, 973.). Topologically different
      peripheral positions, representative of armchair and zigzag borders, exhibit
      different reactivity right from the beginning. Ozone attacks start off either to
      give primary ozonides by concerted addition or, nonconcertedly, to first produce
      trioxyl intermediates. Then, a variety of pathways are described, whose viability
      depends on both model and position. They can open the way to the possible
      formation of epoxide, aldehyde, and phenol groups (all entailing O(2) production)
      or ether (+CO(2)), lactone (+H(2)CO), and ketone functionalities. To sum up,
      functionalization, regardless of how achieved, can give a number of groups, most
      of which actually observed in PAH ozonization experimental studies. This picture
      can be matched up to the results on internal sites of our preceding papers, for
      which epoxidation was the only outcome. Most interestingly, formation of a ketone
      group may turn an even system into an odd one (and conversely) while involving
      production of HOO(*).

PMID- 21175207
TI  - On the accuracy and limits of peptide fragmentation spectrum prediction.
AB  - We estimated the reproducibility of tandem mass spectra for the widely used
      collision-induced dissociation (CID) of peptide ions. Using the Pearson
      correlation coefficient as a measure of spectral similarity, we found that the
      within-experiment reproducibility of fragment ion intensities is very high (about
      0.85). However, across different experiments and instrument types/setups, the
      correlation decreases by more than 15% (to about 0.70). We further investigated
      the accuracy of current predictors of peptide fragmentation spectra and found
      that they are more accurate than the ad-hoc models generally used by search
      engines (e.g., SEQUEST) and, surprisingly, approaching the empirical upper limit
      set by the average across-experiment spectral reproducibility (especially for
      charge +1 and charge +2 precursor ions). These results provide evidence that, in
      terms of accuracy of modeling, predicted peptide fragmentation spectra provide a
      viable alternative to spectral libraries for peptide identification, with a
      higher coverage of peptides and lower storage requirements. Furthermore, using
      five data sets of proteome digests by two different proteases, we find that
      PeptideART (a data-driven machine learning approach) is generally more accurate
      than MassAnalyzer (an approach based on a kinetic model for peptide
      fragmentation) in predicting fragmentation spectra but that both models are
      significantly more accurate than the ad-hoc models.

PMID- 21175208
TI  - Oxidant-free direct coupling of internal alkynes and 2-alkylpyridine via double C
      H activations by alkylhafnium complexes.
AB  - We have developed a novel oxidant-free direct cross-coupling reaction of 2,6
      lutidine and internal alkynes leading to five-membered carbocyclic compounds
      mediated by nonmetallocene cationic hafnium alkyl complexes. Mechanistic studies
      of the coupling reaction showed that the reaction begins with C(sp(3))-H bond
      activation via sigma-bond metathesis, after which the coordinatively unsaturated
      hafnium center mediates further insertion, migration, and beta-H elimination
      reactions to give five-membered carbocycles from readily available substrates.

PMID- 21175209
TI  - Enhanced ionic conductivity in an otherwise poorly conducting Ce0.90Ca0.10O(2
      delta) system.
AB  - A poorly conducting ionic material Ce(0.90)Ca(0.10)O(2-delta) was converted to a
      highly conducting composition by a codoping strategy with Sm(3+) and Gd(3+). A
      50% replacement of Ca with either Sm or Gd has increased the conductivity at 550 
      degrees C of Ce(0.90)Ca(0.10)O(2-delta) from 0.0040 to 0.0169 S/cm for the
      Ce(0.90)Ca(0.05)Sm(0.05)O(2-delta) composition and to 0.0184 S/cm for the
      Ce(0.90)Ca(0.05)Gd(0.05)O(2-delta) composition. The enhancement in the oxide ion
      conductivity of these codoped samples has been related to the low ionic radii
      mismatch and the elastic strain. The extended X-ray absorption fine structure
      measurements on these systems confirmed that Gd, when coupled with Ca, introduced
      more disorder in the system, leading to lower activation energy and higher
      conductivity. In addition, a reduction in the Ce-O bond distance and coordination
      number has also been observed with codoping.

PMID- 21175210
TI  - Generation of highly n-type titanium oxide using plasma fluorine insertion.
AB  - True n-type doping of titanium oxide without formation of midgap states would
      expand the use of metal oxides for charge-based devices. We demonstrate that
      plasma-assisted fluorine insertion passivates defect states and that fluorine
      acts as an n-type donor in titanium oxide. This enabled us to modify the Fermi
      level and transport properties of titanium oxide outside the limits of O vacancy
      doping. The origin of the electronic structure modification is explained by ab
      initio calculation.

PMID- 21175211
TI  - Near-Infrared Reflectance Spectroscopy (NIRS) assessment of delta(18)O and
      nitrogen and ash contents for improved yield potential and drought adaptation in
      maize.
AB  - The oxygen isotope composition (delta(18)O), accumulation of minerals (ash
      content), and nitrogen (N) content in plant tissues have been recently proposed
      as useful integrative physiological criteria associated with yield potential and
      drought resistance in maize. This study tested the ability of near-infrared
      reflectance spectroscopy (NIRS) to predict delta(18)O and ash and N contents in
      leaves and mature kernels of maize. The delta(18)O and ash and N contents were
      determined in leaf and kernel samples from a set of 15 inbreds and 18 hybrids
      grown in Mexico under full irrigation and two levels of drought stress.
      Calibration models between NIRS spectra and the measured variables were developed
      using modified partial least-squares regressions. Global models (which included
      inbred lines and hybrids) accurately predicted ash and N contents, whereas
      prediction of delta(18)O showed lower results. Moreover, in hybrids, NIRS clearly
      reflected genotypic differences in leaf and kernel ash and N contents within each
      water treatment. It was concluded that NIRS can be used as a rapid, cost
      effective, and accurate method for predicting ash and N contents and as a method
      for screening delta(18)O in maize with promising applications in crop management
      and maize breeding programs for improved water and nitrogen use efficiency and
      grain quality.

PMID- 21175212
TI  - Interactions of monoamine oxidases with the antiepileptic drug zonisamide:
      specificity of inhibition and structure of the human monoamine oxidase B complex.
AB  - The binding of zonisamide to purified, recombinant monoamine oxidases (MAOs) has
      been investigated. It is a competitive inhibitor of human MAO B (K(i) = 3.1 +/-
      0.3 MUM), of rat MAO B (K(i) = 2.9 +/- 0.5 MUM), and of zebrafish MAO (K(i) =
      30.8 +/- 5.3 MUM). No inhibition is observed with purified human or rat MAO A.
      The 1.8 A structure of the MAO B complex demonstrates that it binds within the
      substrate cavity.

PMID- 21175213
TI  - A two-coordinate nickel imido complex that effects C-H amination.
AB  - An exceptionally low coordinate nickel imido complex, (IPr*)Ni?N(dmp) (2) (dmp =
      2,6-dimesitylphenyl), has been prepared by the elimination of N2 from a bulky
      aryl azide in its reaction with (IPr*)Ni(eta6-C7H8) (1). The solid-state
      structure of 2 features two-coordinate nickel with a linear C-Ni-N core and a
      short Ni-N distance, both indicative of multiple-bond character. Computational
      studies using density functional theory showed a Ni?N bond dominated by Ni(dpi)
      N(ppi) interactions, resulting in two nearly degenerate singly occupied molecular
      orbitals (SOMOs) that are Ni-N pi* in character. Reaction of 2 with CO resulted
      in nitrene-group transfer to form (dmp)NCO and (IPr*)Ni(CO)3 (3). Net C-H
      insertion was observed in the reaction of 2 with ethene, forming the vinylamine
      (dmp)NH(CH?CH2) (5) via an azanickelacyclobutane intermediate,
      (IPr*)Ni{N,C:kappa2-N(dmp)CH2CH2} (4).

PMID- 21175214
TI  - Photochemical synthesis of phosphinolines from phosphonium-iodonium ylides.
AB  - We describe three different series of experiments which were undertaken to test
      our hypothesis that during irradiation of phosphonium-iodonium ylides (1a, 1b) an
      electrophilic carbene is generated. By opposing the assumed intermediate to
      monosubstituted alkynes, we observed in the case of electron-rich substituents at
      the triple bond a domination of a 1,3-dipolar cycloaddition of the intermediate
      with the triple bond to yield furans. In the case of electron poorer
      substituents, the formation of phosphinolines prevails. A second series of
      experiments was carried out with mixed ylides in which one phenyl ring at the
      triarylphosphonium group was replaced by a thienyl group. In this case, we
      observe only an intramolecular reaction with the thienyl ring to yield the
      phosphinolines 21-23. In a third test, we replaced in the mixed ylides 1a, 1b the
      COR group by a CN substituent. This modification leads to phosphinolines only and
      avoids a 1,3-dipolar cycloaddition.

PMID- 21175216
TI  - Phonon-assisted electron emission from individual carbon nanotubes.
AB  - A question of how electrons can escape from one-atom-thick surfaces has seldom
      been studied and is still not properly answered. Herein, lateral electron
      emission from a one-atom-thick surface is thoroughly studied for the first time.
      We study electron emission from side surface of individual electrically biased
      carbon nanotubes (CNTs) both experimentally and theoretically and discover a new
      electron emission mechanism named phonon-assisted electron emission. A kinetic
      model based on coupled Boltzmann equations of electrons and optical phonons is
      proposed and well describes experimentally measured lateral electron emission
      from CNTs. It is shown that the electrons moving along a biased CNT can overflow
      from the one-atom-thick surface due to the absorption of hot forward-scattering
      optical phonons. A low working voltage, high emission density, and side emission
      character make phonon-assisted electron emission primarily promising in electron
      source applications.

PMID- 21175215
TI  - Enhancing long-range exciton guiding in molecular nanowires by H-aggregation
      lifetime engineering.
AB  - Excitonic transitions in organic semiconductors are associated with large
      oscillator strength that limits the excited-state lifetime and can in turn impede
      long-range exciton migration. We present perylene-based emissive H-aggregate
      nanowires where the lowest energy state is only weakly coupled to the ground
      state, thus dramatically enhancing lifetime. Exciton migration occurs by
      thermally activated hopping, leading to luminescence quenching on topological
      wire defects. An atomic force microscope tip can introduce local topological
      quenchers by distorting the H-aggregate structure, demonstrating long-range
      exciton migration at room temperature and offering a potential route to writing
      fluorescent "nanobarcodes" and excitonic circuits.

PMID- 21175217
TI  - Self-organization of nanoscale multilayer liquid metal films: experiment and
      theory.
AB  - Surfaces made from composite nanostructured materials are potential
      multifunctional platforms for detection, sensing, and energy harvesting in
      biological and inorganic systems. However, robust and cost-effective synthesis
      routes are required to create the required arrays of nanostructures with
      tailorable size, morphology, and composition. Here we show that self-organization
      via spontaneous pattern formation in nanometer thick bilayer liquid films could
      lead to such nanostructure arrays. Experimentally, bilayers of immiscible
      metallic liquids show different self-organized patterning characteristics based
      on their order of arrangement on a substrate. Energy rate theory based on
      equating the rate of free energy change to viscous dissipation was used to
      explain this result. The different bilayer arrangements change the signs of
      intermolecular interactions, which changes the mode of coupled deformations and
      the patterning characteristics. Patterning length scale characteristics from
      nanosecond pulsed laser induced self-organization of Ag and Co liquids on SiO2
      substrate were in good agreement with theory.

PMID- 21175218
TI  - Tunable electrical transport through annealed monolayers of monodisperse cobalt
      platinum nanoparticles.
AB  - We synthesized monodisperse cobalt-platinum nanoparticles Co(0.14-0.22)Pt(0.86
      0.78) of 9 nm in diameter by colloidal chemistry methods and deposited them by
      the Langmuir-Blodgett technique as highly ordered monolayers onto substrates with
      e-beam defined gold electrodes. Upon annealing we observe an increase of
      conductivity over more than 4 orders of magnitude. A first attempt of explanation
      of this unanticipated effect, a nanoparticle displacement, could not be confirmed
      for annealing temperatures below 400  degrees C. A second approach, a
      carbonization of the ligands, however, could be confirmed by Raman spectroscopy.
      The simple thermal treatment allows tuning essential properties of electronic
      devices based on nanoparticles by the manipulation of the interparticle coupling,
      namely the electrical conductivity, the Coulomb blockade characteristic, and the
      activation energy of the system.

PMID- 21175219
TI  - Smiles cascades toward heterocyclic scaffolds.
AB  - Two different Smiles rearrangements can be combined to afford a multicomponent
      formation of isoquinolinones and isoindolinones from nitro methyl salicylate.
      After a Ugi-Smiles four-component coupling, the base-triggered cyclization of the
      resulting adduct is followed by a ring contraction via a Truce-Smiles
      rearrangement.

PMID- 21175220
TI  - High-pressure structural stability and elasticity of supercrystals self-assembled
      from nanocrystals.
AB  - We report here combined quasi-hydrostatic high-pressure small-angle X-ray
      scattering (SAXS) and X-ray diffraction (XRD) studies on faceted 3D supercrystals
      (SCs) self-assembled from colloidal 7.0 nm spherical PbS nanocrystals (NCs).
      Diamond anvil cell (DAC) SAXS experiments in the pressure range from ambient to
      12.5 GPa revealed nearly perfect structural stability of the SCs, with face
      centered cubic organization of the NCs. Pressure-induced ordering (annealing
      effect) of the superstructure was observed. The ambient pressure bulk modulus of
      the SCs was calculated to be ~5 GPa for compression and ~14.5 GPa for
      decompression from fitting of Vinet and Birch-Murnaghan equations of state. XRD
      measurements revealed strong preferential crystallographic orientation of the NCs
      through all phase transformations to as high as 55 GPa without any indication of
      NC sintering. The first phase transition pressure of the NCs was found between
      8.1 and 9.2 GPa and proceeds through homogeneous nucleation. Bulk modulus of PbS
      NCs was calculated to be ~51 GPa based on fitting to the equations of state
      (K(PbS,bulk) ~ 51-57 GPa). Closest surface-to-surface distance between the NCs in
      the SCs was calculated based on combined XRD and SAXS data, to reversibly tune
      from ~1.56 nm to ~0.9-0.92 nm and back to ~1.36 nm in the ambient-12.5 GPa
      ambient pressure cycle. The bulk modulus of the ligand matrix was extrapolated to
      be ~2.2-2.95 GPa. These results show a general method of tuning NC interactions
      in packed nanoparticle solids.

PMID- 21175221
TI  - Langmuir and Langmuir-Blodgett films of multifunctional, amphiphilic polyethers
      with cholesterol moieties.
AB  - Langmuir films of multifunctional, hydrophilic polyethers containing a
      hydrophobic cholesterol group (Ch) were studied by surface pressure-mean
      molecular area (pi-mmA) measurements and Brewster angle microscopy (BAM). The
      polyethers were either homopolymers or diblock copolymers of linear
      poly(glycerol) (lPG), linear poly(glyceryl glycidyl ether) (lPGG), linear
      poly(ethylene glycol) (lPEG), or hyperbranched poly(glycerol) (hbPG). Surface
      pressure measurements revealed that the homopolymers lPG and hbPG did not stay at
      the water surface after spreading and solvent evaporation, in contrast to lPEG.
      Because of the incorporation of the Ch group in the polymer structure, stable
      Langmuir films were formed by Ch-lPG(n), Ch-lPGG(n), and Ch-hbPG(n). The Ch
      hbPG(n), Ch-lPEG(n), Ch-lPEG(n)-b-lPG(m), Ch-lPEG(n)-b-lPGG(m), and Ch-lPEG(n)-b
      hbPG(m) systems showed an extended plateau region assigned to a phase transition
      involving the Ch groups. Typical hierarchically ordered morphologies of the LB
      films on hydrophilic substrates were observed for all Ch-initiated polymers. All
      LB films showed that Ch of the Ch-initiated homopolymers is able to crystallize.
      This strong tendency of self-aggregation then triggers further dewetting effects
      of the respective polyether entities. Fingerlike morphologies are observed for Ch
      lPEG(69), since the lPEG(69) entity is able to undergo crystallization after
      transfer onto the silicon substrate.

PMID- 21175222
TI  - Monocyclic beta-lactams are selective, mechanism-based inhibitors of rhomboid
      intramembrane proteases.
AB  - Rhomboids are relatively recently discovered intramembrane serine proteases that
      are conserved throughout evolution. They have a wide range of biological
      functions, and there is also much speculation about their potential medical
      relevance. Although rhomboids are weakly inhibited by some broad-spectrum serine
      protease inhibitors, no potent and specific inhibitors have been identified for
      these enzymes, which are mechanistically distinct from and evolutionarily
      unrelated to the classical soluble serine proteases. Here we report a new
      biochemical assay for rhomboid function based on the use of quenched fluorescent
      substrate peptides. We have developed this assay into a high-throughput format
      and have undertaken an inhibitor and activator screen of approximately 58,000
      small molecules. This has led to the identification of a new class of rhomboid
      inhibitors, a series of monocyclic beta-lactams, which are more potent than any
      previous inhibitor. They show selectivity, both for rhomboids over the soluble
      serine protease chymotrypsin and also, importantly, between different rhomboids;
      they can inhibit mammalian as well as bacterial rhomboids; and they are effective
      both in vitro and in vivo. These compounds represent important templates for
      further inhibitor development, which could have an impact both on biological
      understanding of rhomboid function and potential future drug development.

PMID- 21175224
TI  - Cyan fluorescent protein carries a constitutive mutation that prevents its
      dimerization.
AB  - The tendency of GFP-like fluorescent proteins to dimerize in vitro is a permanent
      concern as it may lead to artifacts in FRET imaging applications. However, we
      have found recently that CFP and YFP (the couple of GFP variants mostly used in
      FRET studies) show no trace of association in the cytosol of living cells up to
      millimolar concentrations. In this study, we investigated the oligomerization
      properties of purified CFP, by fluorescence anisotropy and sedimentation
      velocity. Surprisingly, we found that CFP has a much weaker homoaffinity than
      other fluorescent proteins (K(d) >= 3 * 10(-3) M), and that this is due to the
      constitutive N146I mutation, originally introduced into CFP to improve its
      brightness.

PMID- 21175227
TI  - Management of inflammatory bowel disease with infliximab and other anti-tumor
      necrosis factor therapies. Foreword.

PMID- 21175223
TI  - C-terminal tyrosine residues modulate the fusion activity of the Hendra virus
      fusion protein.
AB  - The paramyxovirus family includes important human pathogens such as measles,
      mumps, respiratory syncytial virus, and the recently emerged, highly pathogenic
      Hendra and Nipah viruses. The viral fusion (F) protein plays critical roles in
      infection, promoting both the virus-cell membrane fusion events needed for viral
      entry as well as cell-cell fusion events leading to syncytia formation. We
      describe the surprising finding that addition of the short epitope HA tag to the
      cytoplasmic tail (CT) of the Hendra virus F protein leads to a significant
      increase in the extent of cell-cell membrane fusion. This increase was not due to
      alterations in surface expression, cleavage state, or association with lipid
      microdomains. Addition of a Myc tag of similar length did not alter Hendra F
      protein fusion activity, indicating that the observed stimulation was not solely
      a result of lengthening the CT. Three tyrosine residues within the HA tag were
      critical for the increase in the extent of fusion, suggesting C-terminal
      tyrosines may modulate Hendra fusion activity. The effects of addition of the HA
      tag varied with other fusion proteins, as parainfluenza virus 5 F-HA showed a
      decreased level of surface expression and no stimulation of fusion. These results
      indicate that additions to the C-terminal end of the F protein CT can modulate
      protein function in a sequence specific manner, reinforcing the need for careful
      analysis of epitope-tagged glycoproteins. In addition, our results implicate C
      terminal tyrosine residues in the modulation of the membrane fusion reaction
      promoted by these viral glycoproteins.

PMID- 21175228
TI  - Management of inflammatory bowel disease with infliximab and other anti-tumor
      necrosis factor alpha therapies.
AB  - Inflammatory bowel disease (IBD), most commonly referring to Crohn's disease and
      ulcerative colitis, is a chronic and disabling condition with an increasing
      incidence in southern Europe. The etiology of IBD remains unknown, but the
      characteristic disproportionate inflammatory response in the gut may develop
      through various mechanisms at the cellular and subcellular level. Tumor necrosis
      factor (TNF) alpha is one crucial mediator of this abnormal immune response, and
      in recent years, biological therapies targeting TNFalpha have significantly
      improved the management of IBD refractory to conventional therapies. Infliximab
      is the best studied anti-TNFalpha agent, and is currently approved in the
      European Union for adults and children with Crohn's disease and adults with
      ulcerative colitis; adalimumab is indicated for Crohn's disease in adults but not
      children, while certolizumab was not approved in the European Union for Crohn's
      disease. Infliximab has confirmed efficacy in adults with Crohn's disease
      (including fistulizing disease) and ulcerative colitis, with benefits observed in
      both clinical remission and mucosal healing, it is similarly effective in
      children with Crohn's disease. Evidence suggests that early treatment with
      infliximab may improve the natural course of the disease. Adalimumab showed
      efficacy in adults with Crohn's disease and more limited data suggest efficacy in
      children with Crohn's disease. Although certolizumab pegol has also shown
      promising data in adults with Crohn's disease, data in children are lacking. Anti
      TNFalpha agents are generally well tolerated, although careful monitoring for
      adverse events such as infections, infusion reactions, lymphomas and
      demyelinating diseases is warranted. A definitive causal relationship between
      anti-TNFalpha agents and various adverse events is difficult to establish, as the
      underlying disease and concomitant immunosuppression also predispose patients to
      such events. Infliximab has not been associated with an increased incidence of
      serious events, and adalimumab and certolizumab are also generally well tolerated
      in clinical trials. Both adalimumab and certolizumab pegol are associated with
      lower levels of drug antibodies compared with infliximab. Reactivation of latent
      tuberculosis is a potential risk with any anti-TNFalpha agent, and identification
      and treatment is required before initiating therapy. Although causal
      relationships are difficult to establish, caution is advised with anti-TNFalpha
      compounds in patients developing neurological symptoms suggestive of
      demyelinating disease, or in those at high risk of malignancy. Infliximab is also
      generally well tolerated in children; however, data are scarce for the other
      compounds. No increased risks associated with pregnancy have been observed for
      infliximab or adalimumab, but caution in pregnancy and during breast-feeding is
      currently advocated. In terms of future research, more long-term data are needed
      for both certolizumab pegol in Crohn's disease and adalimumab in ulcerative
      colitis. More research on the benefits of early biological treatment on disease
      progression is needed. In summary, the anti-TNFalpha inhibitors represent a
      momentous advance in the treatment of Crohn's disease and ulcerative colitis
      refractory to conventional treatments. They offer significant benefits in quality
      of life and mucosal healing, and may have the potential to change the evolution
      of the disease when given early.

PMID- 21175229
TI  - Secondary amyloidosis in a patient with long duration Crohn's disease treated
      with infliximab.
AB  - Systemic AA amyloidosis is a serious complication of many chronic inflammatory
      disorders. Its association with Crohn's disease implies that the inflammatory
      burden is high enough for amyloid fibrils to form deposits in tissues. A case is
      presented in which this complication occurred while the patient was clinically
      well, with biological and endoscopic markers showing an inactive or mildly active
      disease under anti-tumor necrosis factor alpha therapy.

PMID- 21175230
TI  - Colon cancer after infliximab therapy for Crohn's disease.
AB  - Infliximab is an effective agent in the treatment of patients with Crohn's
      disease. Therapy with infliximab is generally well tolerated but there are
      concerns about its effects on the incidence of cancer. This case report refers to
      a 47-year-old patient with long-standing Crohn's disease, without a family
      history of colorectal cancer, who had a previous diagnosis of low-grade dysplasia
      that was not confirmed in subsequent studies, and was diagnosed with
      adenocarcinoma of the colon with peritoneal invasion after the fourth infusion of
      infliximab.

PMID- 21175231
TI  - Infliximab aids recovery of anal continence in a patient with perianal Crohn's
      disease.
AB  - Perianal complications occur in approximately 33% of patients with Crohn's
      disease, and may be the most prominent or even the presenting complaint
      suggestive of a diagnosis of Crohn's disease. A case is reported of severe
      perianal Crohn's disease with anal destruction and incontinence that developed
      after perianal surgery. Healing of perianal lesions and recovery of anal function
      was achieved with infliximab therapy.

PMID- 21175232
TI  - Autoimmune hepatitis induced by infliximab in a patient with Crohn's disease with
      no relapse after switching to adalimumab.
AB  - Infliximab and adalimumab are anti-tumor necrosis factor (TNF) alpha agents used
      for treating Crohn's disease. Autoimmune hepatitis (AIH) is a rare complication
      of treatment with these drugs. We report on a case of AIH in a patient with
      Crohn's disease treated with infliximab who fully recovered after drug
      withdrawal. More interestingly, because there were no other treatment options,
      the patient was then treated with adalimumab without recurrence of the liver
      disease and with control of the intestinal disease.

PMID- 21175233
TI  - Complete resolution of enterocolic fistulas with infliximab.
AB  - Fistulas are a frequent and serious complication of Crohn's disease. Most of the
      literature has been focused on perianal fistulas, which are by far the most
      frequent. The effectiveness of treatment with infliximab in fistulizing Crohn's
      disease was demonstrated in the ACCENT II trial. In that study, however, all
      patients had external fistulas, and the majority of those were perianal fistulas.
      The response to fistula treatment in other locations was not evaluated.

PMID- 21175234
TI  - Crohn's disease in a child: unusual presentation with severe osteoporosis.
AB  - Crohn's disease is a chronic inflammatory bowel disease characterized by
      transmural, granulomatous inflammation. In paediatric-onset Crohn's disease, the
      most frequent clinical features are abdominal pain, diarrhoea, fatigue and weight
      loss. Delayed puberty, growth retardation and osteoporosis might, however, be the
      predominant signs of the disease. This paper reports the case of a 13-year-old
      girl with Crohn's disease diagnosed at the age of 11 years, with classic
      gastrointestinal symptoms in the previous few months, but with severe
      osteoporosis at onset. The child has been on infliximab therapy for 1 year, with
      complete control of the disease. Therapy with infliximab appears to influence
      bone metabolism, bone formation and resorption, and that improvement seems to be
      independent of the clinical response to the drug. Infliximab has recently been
      approved for paediatric use, which has been a great improvement for a group of
      patients lacking therapeutic options.

PMID- 21175235
TI  - Ulcerative colitis: history of a successful treatment.
AB  - In this report we describe a case of a 19-year-old woman with a severe to
      fulminant steroid-resistant ulcerative colitis that was successfully treated with
      infliximab. Severe to fulminant ulcerative colitis is a potentially life
      threatening condition and although the mortality rate has dropped dramatically
      over the past 40 years, this has not been the case with colectomy which has
      remained unchanged. Recently, infliximab has been shown to be effective as rescue
      therapy for steroid-refractory cases.

PMID- 21175236
TI  - Association of ankylosing spondylitis and Crohn's disease successfully treated
      with infliximab.
AB  - In patients with inflammatory bowel disease (IBD) the prevalence of ankylosing
      spondylitis is 4-10%, and approximately 5-10% of ankylosing spondylitis patients
      have concomitant IBD. The correct recognition of spondyloarthritides is essential
      in order to identify common therapeutic strategies, especially in the era of new
      biological therapies such as infliximab. This paper reports a case of a patient
      with a severe presentation of ankylosing spondylitis and Crohn's disease
      successfully treated with infliximab. Two important points concerning this case
      are discussed: one is the true value of non-steroidal anti-inflammatory drug
      induced IBD exacerbation and the other is the role of anti-tumor necrosis factor
      agents (especially infliximab) in the treatment of patients with concomitant
      diseases.

PMID- 21175237
TI  - Should prophylactic low-dose aspirin therapy be continued in peptic ulcer
      bleeding?
AB  - Patients taking low-dose aspirin for cardiovascular prevention who develop an
      acute peptic ulcer bleeding event represent a serious challenge in clinical
      practice. Aspirin discontinuation is associated with increased risk of developing
      a new cardiovascular event, but there is little evidence on the outcomes and best
      management strategy in the setting of an acute ulcer bleeding event. In this
      clinical scenario, it is common clinical practice to interrupt aspirin treatment
      for various, sometimes long, periods of time. A recent study suggests that
      patients with bleeding ulcers who keep taking aspirin after successful endoscopic
      therapy followed by high-dose intravenous pantoprazole, bolus of 80 mg followed
      by 8 mg/h for 3 days, have a small increase in the risk of rebleeding but a lower
      overall and cardiovascular 30-day mortality rate than those who stop taking
      aspirin treatment. Based on current, although limited, data, we propose that
      these patients should undergo early endoscopic therapy to control bleeding
      followed by a high-dose intravenous PPI, with early reintroduction of aspirin
      treatment within a 5-day window after the last dose. However, in patients taking
      aspirin for the primary prevention of cardiovascular events, it seems reasonable
      to stop aspirin treatment, re-evaluate the indication and, if needed, reintroduce
      aspirin after the risk of ulcer rebleeding decreases, usually after hospital
      discharge. In the presence of an acute ulcer bleeding event soon after the
      placement of coronary stents, the risk of stent thrombosis with removal of
      antiplatelet therapy is very high. We believe that early therapeutic endoscopy
      and a high-dose intravenous PPI is advisable in order to maintain patients on
      dual antiplatelet therapy. Until more evidence becomes available, clinicians will
      have to rely on actual data and the use of common sense to select the best option
      for the patient.

PMID- 21175239
TI  - If at first you don't succeed: a review of the evidence for antidepressant
      augmentation, combination and switching strategies.
AB  - Major depressive disorder is a common and disabling illness that leads to
      significant reductions in quality of life and considerable cost to society.
      Despite numerous advances in the pharmacological treatment of depression, many
      patients remain ill despite initial treatment. Beyond first-line treatment,
      current guidelines recommend either augmentation or switching of the initial
      antidepressant. In this narrative review, we summarize the data from randomized
      controlled trials and meta-analyses in order to concisely discuss how the impact
      of current research can be translated into clinical practice and, ultimately,
      into lasting improvements in patient outcomes. The augmentation strategies
      reviewed are lithium, thyroid hormone, pindolol, psychostimulants and second
      generation antipsychotics. The data on switching from first-line antidepressants
      to other antidepressants are also reviewed, and include switching within the same
      class, switching to other first-line antidepressant classes and switching to less
      commonly prescribed antidepressants. Finally, the strategy of antidepressant
      combinations is examined. Overall, the strength of evidence supporting a trial of
      augmentation or a switch to a new agent is very similar, with remission rates
      between 25% and 50% in both cases. Our review of the evidence suggests several
      conclusions. First, although it is true that adjunctive lithium and thyroid
      hormone have established efficacy, we can only be confident that this is true for
      use in combination with tricyclic antidepressants (TCAs), and the trials were
      done in less treatment-resistant patients than those who typically receive TCAs
      today. Of these two options, triiodothyronine augmentation seems to offer the
      best benefit/risk ratio for augmentation of modern antidepressants. After failure
      of a first-line selective serotonin reuptake inhibitor (SSRI), neither a switch
      within class nor a switch to a different class of antidepressant is unequivocally
      supported by the data, although switching from an SSRI to venlafaxine or
      mirtazapine may potentially offer greater benefits. Interestingly, switching from
      a newer antidepressant to a TCA after a poor response to the former is not
      supported by strong evidence. Of all strategies to augment response to new
      generation antidepressants, quetiapine and aripiprazole are best supported by the
      evidence, although neither the cost effectiveness nor the longer-term benefit of
      these strategies has been established. The data to guide later steps in the
      treatment of resistant depression are sparse. Given the wide variety of options
      for the treatment of major depressive disorder, and the demonstrated importance
      of truly adequate treatment to the long-term outcomes of patients facing this
      illness, it is clear that further well conducted studies are needed.

PMID- 21175240
TI  - Antifracture efficacy of currently available therapies for postmenopausal
      osteoporosis.
AB  - Osteoporosis is a systemic bone disease characterized by low bone mass and bone
      mineral density, and deterioration of the underlying structure of bone tissue.
      These changes lead to an increase in bone fragility and an increased risk for
      fracture, which are the clinical consequences of osteoporosis. The classical
      triad for consideration in osteoporosis is morbidity, mortality and cost.
      Vertebral fracture is an important source of morbidity in terms of pain and
      spinal deformity. On the other hand, hip fracture is associated with the worst
      outcomes and is widely regarded as a life-threatening event in the elderly; it is
      the source of the bulk of the cost of the disease in contemporary healthcare. The
      prevention of osteoporosis-associated fracture should include fall prevention,
      calcium supplementation and lifestyle advice, as well as pharmacological therapy
      using agents with proven antifracture efficacy. The most commonly used
      osteoporosis treatments in Europe are the bisphosphonates alendronate,
      risedronate, ibandronate and zoledronic acid; the selective estrogen receptor
      modulator (SERM) raloxifene; teriparatide; and strontium ranelate. Recent
      additions include the biological therapy denosumab and the SERM bazedoxifene. In
      this review, we explore the antifracture efficacy of these agents with the aim of
      simplifying treatment decisions. These treatments can be broadly divided
      according to their mode of action. The antiresorptive agents include the
      bisphosphonates, the SERMs and denosumab, while the bone-forming agents include
      parathyroid hormone and teriparatide. Strontium ranelate appears to combine both
      antiresorptive and anabolic activities. We collated data on vertebral and hip
      fracture efficacy from the pivotal 3-year phase III trials, all of which had a
      randomized, double-blind, placebo-controlled design. The relative reductions in
      risk in the osteoporosis trials range from 30% to 70% for vertebral fracture and
      30% to 51% for hip fracture. This translates into 3-year number needed to treat
      values of between 9 and 21 for vertebral fracture and from 48 upwards for hip
      fracture. International guidelines agree that agents that have been shown to
      decrease vertebral, nonvertebral and hip fractures should be used preferentially
      over agents that only demonstrate vertebral antifracture efficacy. This is the
      case for alendronate, risedronate, zoledronic acid, denosumab and strontium
      ranelate. Finally, therapeutic decisions should be based on a balance between
      benefits and risks of treatment, which must be carefully considered in each
      particular case both by the physician and the patient. Indeed, no single agent is
      appropriate for all patients and, therefore, treatment decisions should be made
      on an individual basis, taking into account all measures of treatment effect and
      risk before making informed judgments about the best individual treatment option.

PMID- 21175238
TI  - Echinocandin antifungal drugs in fungal infections: a comparison.
AB  - This review compares the pharmacology, spectrum of antifungal activity,
      pharmacokinetic and pharmacodynamic properties, safety and clinical efficacy of
      the three licensed echinocandins: caspofungin, micafungin and anidulafungin.
      Echinocandins inhibit the synthesis of 1,3-beta-D-glucan, an essential component
      of the fungal cell wall, and represent a valuable treatment option for fungal
      infections. The echinocandins exhibit potent in vitro and in vivo fungicidal
      activity against Candida species, including azole-resistant pathogens. For all
      agents, strains with drug minimum inhibitory concentrations (MICs) of <= 2 MUg/mL
      are considered susceptible; the MIC at which 90% of isolates tested were
      inhibited (MIC90) values are typically <2 MUg/mL but 100-fold higher MIC90 values
      are seen with Candida parapsilosis (1-2 MUg/mL) and Candida guilliermondii (1-4
      MUg/mL). Activity is comparable between the three agents, although limited data
      indicate that anidulafungin may have low MICs against C. parapsilosis and Candida
      glabrata strains that demonstrate elevated MICs to caspofungin and micafungin.
      All three drugs have good fungistatic activity against Aspergillus spp., although
      minimal effective concentrations of micafungin and anidulfungin are 2- to 10-fold
      lower than those for caspofungin. Synergistic/additive in vitro effects of
      echinocandins when combined with a polyene or azole have been observed. Clinical
      resistance to the echinocandins is rare despite case reports of caspofungin
      resistance in several Candida spp. Resistance has been attributed to mutations in
      the FKS1 gene within two hot spot regions, leading to amino acid substitutions,
      mostly at position 645 (serine), yet not all FKS1 mutants have caspofungin MICs
      of >2 MUg/mL. Of the three echinocandins, the in vitro 'paradoxical effect'
      (increased growth at supra-MIC drug concentrations) is observed least often with
      anidulafungin. All echinocandins have low oral bioavailability, and distribute
      well into tissues, but poorly into the CNS and eye. Anidulafungin is unique in
      that it undergoes elimination by chemical degradation in bile rather than via
      hepatic metabolism, has a lower maximum concentration and smaller steady state
      under the concentration-time curve but longer half-life than caspofungin or
      micafungin. In children, dosing should be based on body surface area. Daily doses
      of caspofungin (but not micafungin and anidulafungin) should be decreased (from
      50 to 35 mg) in moderate liver insufficiency. All echinocandins display
      concentration-dependent fungicidal (for Candida) or fungistatic (for Aspergillus)
      activity. The postantifungal effect is 0.9-20 hours against Candida and <0.5
      hours against Aspergillus. The echinocandins are well tolerated with few serious
      drug-drug interactions since they are not appreciable substrates, inhibitors or
      inducers of the cytochrome P450 or P-glycoprotein systems. In parallel with the
      greater clinical experience with caspofungin, this agent has a slightly higher
      potential for adverse effects/drug-drug interactions, with the least potential
      observed for anidulafungin. Caspofungin (but not micafungin or anidulafungin)
      dosing should be increased if coadministered with rifampicin and there are modest
      interactions of caspofungin with calcineurin inhibitors. All three agents are
      approved for the treatment of oesophageal candidiasis, candidaemia and other
      select forms of invasive candidiasis. Only micafungin is licensed for antifungal
      prophylaxis in stem cell transplantation, whereas caspofungin is approved for
      empirical therapy of febrile neutropenia. Caspofungin has been evaluated in the
      salvage and primary therapy of invasive aspergillosis. Combination regimens
      incorporating an echinocandin showing promise in the treatment of aspergillosis.
      However, echinocandins remain expensive to use.

PMID- 21175241
TI  - Optimal management of patients with non-small cell lung cancer and epidermal
      growth factor receptor mutations.
AB  - In recent years, the epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitors (TKIs), gefitinib and erlotinib, which have promising activity and a
      favourable toxicity profile, have been used in the management of advanced non
      small cell lung cancer (NSCLC). The knowledge that EGFR-activating mutations
      confer sensitivity to EGFR TKIs has led to the design and analysis of phase II
      and III studies of gefitinib or erlotinib treatment in various clinical
      scenarios. We review the important NSCLC clinical trials of the efficacy of EGFR
      TKIs in the context of EGFR-activating mutations. In all phase II single-arm
      studies or phase III randomized comparative studies, EGFR TKIs as monotherapy
      were superior to combination chemotherapy in terms of response rate and
      progression-free survival in patients with activating EGFR mutations. EGFR TKIs
      have contributed to the superior overall survival time in NSCLC patients with
      EGFR mutations compared with those patients without EGFR mutations. The results
      of these studies have led to a paradigm shift in the treatment of patients with
      advanced NSCLC. NSCLC with EGFR mutations constitutes a new entity requiring
      different personalized treatment strategies.

PMID- 21175242
TI  - Moxifloxacin 0.5% ophthalmic solution: in bacterial conjunctivitis.
AB  - The fourth-generation 8-methoxyfluoroquinolone moxifloxacin is available as an
      0.5% ophthalmic solution for use in the treatment of bacterial conjunctivitis.
      Moxifloxacin had good activity against various Gram-positive and -negative ocular
      isolates in vitro, and moxifloxacin 0.5% ophthalmic solution achieved good
      penetration into ocular tissues in healthy volunteers and patients undergoing
      ocular surgery. The efficacy of moxifloxacin 0.5% ophthalmic solution in the
      treatment of bacterial conjunctivitis has been shown in three randomized, double
      blind, multicentre trials. In a trial in patients aged >=1 year, the clinical
      success rate was significantly higher with moxifloxacin 0.5% ophthalmic solution
      than with placebo. In a trial in patients aged >=12 years, moxifloxacin 0.5%
      ophthalmic solution was noninferior to levofloxacin 0.5% ophthalmic solution in
      terms of the clinical success rate. In a third trial, the clinical cure rate was
      significantly higher with moxifloxacin 0.5% ophthalmic solution than with
      trimethoprim 1.0%/polymixin B 10,000 IU/mL ophthalmic solution in paediatric
      patients aged <=18 years. Moxifloxacin 0.5% ophthalmic solution was well
      tolerated in patients with bacterial conjunctivitis. Ocular adverse events (e.g.
      eye pain, eye irritation) were the most commonly reported treatment-related
      adverse events, with the majority being of mild severity.

PMID- 21175243
TI  - Sipuleucel-T: in metastatic castration-resistant prostate cancer.
AB  - Sipuleucel-T is an autologous active cellular immunotherapy used in the treatment
      of men with asymptomatic or minimally symptomatic metastatic castration-resistant
      prostate cancer (CRPC). It is the first therapeutic cancer vaccine to receive US
      FDA approval. Approximately 3 days prior to each infusion of sipuleucel-T,
      patients undergo a leukapheresis procedure for collection of autologous
      peripheral blood mononuclear cells. Preparation of sipuleucel-T involves
      enrichment for antigen-presenting cells from the leukapheresis product and
      activation ex vivo with a recombinant fusion protein (PA2024). In the randomized,
      double-blind, placebo-controlled IMPACT study in patients with metastatic CRPC,
      sipuleucel-T was associated with a 22% relative reduction in the risk of death
      (hazard ratio 0.78; p = 0.03), which was the primary endpoint of the trial. After
      a median follow-up period of 34.1 months, median survival was 4.1 months longer
      with sipuleucel-T than placebo (25.8 vs 21.7 months). There was no significant
      between-group difference for the median time to objective disease progression (a
      secondary endpoint). Almost all patients treated with sipuleucel-T in clinical
      trials reported an adverse event, although these were mild or moderate in
      severity (grade 1 or 2) in most patients. The most common adverse events (e.g.
      infusion-related events, such as chills and fever) generally occurred within the
      first day after administration of sipuleucel-T and resolved within 2 days.

PMID- 21175245
TI  - Toll-like receptors in immune response to the viral infections.
AB  - Toll-like receptors (TLRs) are members of the innate immunity system. They are
      responsible for the recognition of various antigens and take part in the
      modulation of immunity responses. In general, they are divided into "bacterial"
      and "viral" TLRs, even though this classification overlaps in some cases. Genetic
      similarity of TLRs gives them the status of highly conservative proteins
      throughout the animal kingdom. However, there is a certain level of variation
      between different species that can result in semi-disparate recognition ability.
      Furthermore, their universal signaling pathways predispose them not only as a
      target for vaccination trials in humans, but also for the genetic selection in
      veterinary medicine. Moreover, the selection pressure and their conservative
      properties make them a suitable system for the evolutionary studies, since each
      separate genetic system has its own unique ortholog/paralog. TLRs 2, 3, 4, 7, 8,
      and 9 play a crucial role in the recognition and modulation of the innate
      immunity in response to the viral infection due to their predominant localization
      on the white blood cells and endothelial cells, while intracellularly localized
      TLRs lead the way.

PMID- 21175244
TI  - Histamine dihydrochloride: in the management of acute myeloid leukaemia.
AB  - Histamine dihydrochloride (Ceplene) is a synthetic derivative of the biogenic
      amine histamine. Histamine dihydrochloride inhibits the formation of reactive
      oxygen species that suppress the activation of T cells and natural killer cells.
      When administered in addition to the cytokine interleukin (IL)-2, histamine
      dihydrochloride enables the activation of T cells and natural killer cells by IL
      2, resulting in the killing of tumour cells of various cancers, including acute
      myeloid leukaemia (AML). In a 3-year, randomized, multicentre, phase III trial in
      adult patients with AML in first or subsequent remission, those who received
      subcutaneous histamine dihydrochloride and concomitant subcutaneous IL-2 as
      maintenance therapy had a significantly longer leukaemia-free survival (LFS;
      primary endpoint) than recipients of no treatment. This difference was also shown
      for the subgroup of patients in first remission. The between-group difference in
      overall survival (OS) was not significant, although this trial was not powered to
      detect such a difference. Histamine dihydrochloride and IL-2 therapy had an
      acceptable tolerability profile in patients in the phase III trial. The majority
      of reported adverse events were grade 1 or 2 of the National Cancer Institute
      Common Toxicity Criteria. The most commonly reported grade 3 adverse events with
      active treatment were thrombocytopenia, headache, neutropenia, pyrexia,
      eosinophilia and diarrhoea; grade 4 adverse events were thrombocytopenia and
      leukopenia not otherwise specified. Serious adverse events were mostly relapse
      related. Histamine dihydrochloride and IL-2 as maintenance therapy significantly
      prolonged LFS compared with no treatment and had an acceptable tolerability
      profile in a large phase III trial in patients with AML. Although some issues
      remain to be addressed, most notably the effects of therapy on OS and the
      efficacy of treatment in older patients, histamine dihydrochloride in addition to
      IL-2 appears to be a useful maintenance therapy option for adult patients with
      AML in remission.

PMID- 21175246
TI  - Variation of human papillomavirus 16 in cervical and lung cancers in Sichuan,
      China.
AB  - Although the crucial role of human papillomaviruses (HPVs), especially HPV-16 in
      various cancers has been confirmed, the variation of HPV-16 among different
      cancers have not been investigated in a specific geographic location. In order to
      elucidate whether similar HPV-16 variants are involved in different kinds of
      cancers in the same geographic location, the analysis of sequence variants of E6
      and E7 oncogenes and L1 gene of HPV-16 in cervical and lung cancers in Sichuan,
      China, was carried out. Tissue samples from 122 cervical cancers, 104 lung
      cancers, and 138 controls were subjected to RT-PCR or PCR, sequencing, and
      sequence analysis. The infection rates of HPV-16 in cervical, lung cancers, and
      non-malignant controls were 68.9%, 17.3%, and 37.0%, respectively. Asian
      prototype variants prevailed in cervical and lung cancers, while European
      prototype variants in non-malignant controls. In comparison to the lung cancer,
      cervical cancer showed a much higher diversity of HPV-16 oncogenes. These results
      indicate that in Sichuan, China, Asian prototype variants of HPV-16 are more
      pathogenic than their European counterparts.

PMID- 21175247
TI  - New phylogenetically distinct cyanophages found in the coastal Yellow Sea by
      Qingdao.
AB  - Genetic composition of natural cyanophage population in the coastal Yellow Sea
      area near Qingdao was investigated using the g20 gene as a genetic marker.
      Amplification of this gene by PCR yielded sequences, which were cloned and
      subjected to the restriction fragment length polymorphism (RFLP) analysis.
      Sixteen clones exhibiting different RFLP patterns were sequenced and analyzed.
      The sequence analysis indicated a diversity of cyanophages covering sixteen g20
      genotypes. Their phylogenetic analysis revealed two distinct phylogenetic groups.
      One group (7clones) localized with the cyanophage P77 in the cluster III
      described before. Second group (9 clones) did not localize with any of the
      cyanophage described so far and was designated as a novel W cluster. The study
      revealed a genetic diversity of cyanophages in the coastal Yellow Sea and
      confirmed the genetic differences between cyanophage populations in Western and
      Eastern Pacific.

PMID- 21175248
TI  - Keratinocytes play a role in the immunity to Herpes simplex virus type 2
      infection.
AB  - Herpes simplex virus type 2 (HSV-2) infection is the most common cause of genital
      ulcerative disease in the developed world. Keratinocytes are the primary cells
      involved in clinical lesions caused by HSV-2. In our study, we intensively
      examined cytokine expression in the HSV-2-infected keratinocytes. We observed
      upregulation of a series of cytokines including early-induced antiviral cytokines
      as interferons alpha, beta (IFN-alpha, beta), tumor necrosis factor alpha (TNF
      alpha), colony stimulating factors (CSFs) as G-CSF, GM-CSF, interleukin 3 (IL-3),
      growth factors (EGF, KGF, and IGF-beta1), defensins, selectins, leukocyte
      function-associated antigens (LFAs,) and toll-like receptors (TLR-2, 3, 4, and
      9). More importantly, we found that HSV-2-infected keratinocytes stimulated the
      proliferation of lymphocytes in co-cultivation system. These data suggest that
      keratinocytes participate in the immune response to HSV-2 infection in two ways.
      They secrete inflammatory cytokines to resist the HSV-2 infection directly and
      recruit the immune cells to eliminate the primary infection indirectly and
      enhance the adaptive immunity to prevent subsequent infections.

PMID- 21175249
TI  - A recombinant rabies virus expressing luciferase.
AB  - A recombinant Rabies virus (RV) expressing firefly luciferase (rRV-luc) was
      generated by an improved reverse genetics system. Its biological properties were
      compared with those of the parental RV. The rRV-luc grew in BHK-21 cells
      similarly to RV, but its virulence for mice was weaker as shown by the lower
      infectious titers in brain. Rising infectious titers of rRV-luc during its
      passaging in BHK-21 cells indicated a virus adaptation, while the luciferase
      (luc) expression was stable. These results suggest that the recombinant RV
      carrying luc gene might prove a useful tool for further analysis of pathogenesis
      of RV in small animal models.

PMID- 21175250
TI  - Characterization of ORF29 of Bombyx mori nucleopolyhedrovirus.
AB  - ORF 29 of Bombyx mori nucleopolyhedrovirus (BmNPV ORF29), a conserved gene among
      all the lepidopteran baculoviruses, was subjected to analysis of sequence and
      transcription/translation in the insect BmN cells in vitro. His-tagged BmNPV
      ORF29 fusion protein was expressed in Escherichia coli, purified and used for the
      production of an antiserum. All the homologs of BmNPV ORF29 in baculoviruses
      contain a Nudix motif with slight modifications in the N-terminal part. A 654 nts
      long transcript of BmNPV ORF29 in BmN cells was detected at 3-48 hrs p.i.
      indicating the early nature of the gene. In the virus-infected cells, the BmNPV
      ORF29 protein of 26 K was present in both the cytoplasm and nucleus. In the
      virions, the protein was present in Budded virus (BV), but not in Occlusion
      derived virus (ODV). These results suggest that BmNPV ORF29 is a functional ORF
      of BmNPV, which encodes a 26 K protein expressed in the early stage of infection
      cycle.

PMID- 21175251
TI  - Evidence for the adaptive evolution of ORF5 gene of Porcine reproductive and
      respiratory syndrome virus isolated in China.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) ORF5 gene encoding an
      envelope glycoprotein involved in humoral immunity is the most variable protein
      coding gene of PRRSV. The present study aimed to identify potential selective
      pressures acting on the ORF5 gene of PRRSV isolates of North American type
      prevalent in China. The non-synonymous to synonymous rate ratio omega (dN/dS) was
      employed as a measure of selective pressure at the codon level. An overall omega
      of 0.45 indicated negative (purifying) selection as the major driving force
      operating on the ORF5 gene during adaptation of the virus to swine. Determination
      of omega values for individual amino acids sites revealed 8 positively selected
      sites, most of them situated in the N-terminal ectodomain, indicating their
      potential role in the binding of virus to the cellular receptors. Further, 75
      negatively selected sites were identified in the rest of molecule, probably as a
      result of functional or immunological constraints. Determination of potential N
      glycosylation sites revealed 7 sites, four of which coincided with the positively
      selected ones. These results indicated that a specific adaptive evolution has
      operated on the ORF5 gene of Chinese PRRSV isolates. It is hoped that the
      disclosed adaptive sites might help identify a candidate antigenic epitope for
      the use in vaccine against this serious swine disease.

PMID- 21175252
TI  - Establishment of cell lines latently infected with non-oncogenic murine
      gammaherpesvirus 76.
AB  - Murine gammaherpesviruses 68 (MHV-68) and 78 (MHV-78), both inducing tumors in
      mice and a latent infection in cells in vitro, serve as models for study of human
      oncogenic gammaherpesviruses, namely Epstein-Barr virus (EBV) and Kaposi's
      sarcoma-associated herpesvirus (KSHV). In this work, we succeeded in establishing
      a latent infection of HeLa and CGL1 cell lines with non-oncogenic murine
      gammaherpesvirus 76 (MHV-76), which differs from MHV-68 and MHV-78 besides by
      oncogenicity also by deletion of M1-M4 genes and eight tRNA-like sequences. Viral
      latency in these cell lines, lambdaHeLa and lambdaCGL1, was demonstrated by the
      presence of viral DNA, suppression of viral latency-associated ORF73 gene and
      appearance of low amounts of infectious virus following treatment with phorbol 12
      myristate 13-acetate (PMA). Both latently infected cell lines showed irregular
      presence of viral antigen originating apparently from spontaneous reactivation.
      The growth of latently infected cells in culture was similar to that of non
      infected ones. The latently-infected lambdaHeLa cells did not induce tumors in
      mice following subcutaneous inoculation. These results (i) confirm that MHV-76 is
      the only non-oncogenic murine gammaherpesvirus of all the so far tested ones,
      (ii) suggest that some of the genes deleted in MHV-76 might be responsible for
      the oncogenicity of murine gammaherpesviruses, (iii) confirm that viral ORF73 is
      one of major latency-associated genes that is suppressed during virus
      reactivation, and (iv) present MHV-76 as another murine gammaherpesvirus useful
      as a model for study of gammaherpesvirus pathogenesis, oncogenicity, latency and
      reactivation.

PMID- 21175253
TI  - Immune responses of mice to prime-boost vaccination with the recombinant DNA and
      Fowlpox virus both expressing HIV-2 Gag-gp105.
AB  - Human immunodeficiency viruses 1 and 2 (HIV-1, 2) present a public health problem
      for which there is neither an effective antiviral therapy nor a preventive
      vaccine. In this study, the immune responses of mice to prime-boost vaccination
      with the recombinant DNA (rDNA) and recombinant Fowlpox virus (rFPV) both
      expressing HIV-2 Gag-gp105 chimeric protein, were compared to those elicited by
      each vector alone. Mice primed with the rDNA and boosted with the rFPV showed HIV
      2-specific antibody levels, splenic CD4+ and CD8+ T-lymphocyte numbers, and Gag
      gp105-specific cytotoxic T-lymphocytes (CTL) activity increased by 20-30% as
      compared with those elicited by these vaccines alone. These findings suggested
      that the prime-boost strategy combining rDNA and rFPV elicited significant Gag
      gp105 - specific cellular and humoral immune responses, thus supporting this
      novel approach to the immunization against HIV infections.

PMID- 21175254
TI  - Establishment of the cell line expressing human prion protein on PrP0/0
      background.
AB  - In this work we described preparation of the novel cell lines expressing human
      prion protein on PrP0/0-background. Prepared cell lines originated from the
      Nagasaki mice (PrP0/0) and showed a fibroblast phenotype. The expression level of
      human prion protein in the developed cell lines was comparable to the
      physiological expression measured in GT1-7 cells. A great advantage of the
      prepared cell lines was their short doubling time that allowed obtaining of a
      large amount of cells for the proteomic experiments. Newly established cell lines
      open a broad spectrum of applications in the prion research. Besides the study of
      physiological function of the prion protein or its interactome, the new cell
      lines could be successfully employed as a unique tool for the better
      understanding of key events in the pathogenesis of prion diseases.

PMID- 21175255
TI  - Simple and efficient biolistic procedure for the plant transfection with cDNA
      clones of RNA viruses.
AB  - Simple, fast, low-cost, and efficient procedure for DNA delivery to the cell
      nuclei of whole plants was developed. The procedure was optimized for the Plum
      pox virus (PPV) and its host Nicotiana benthamiana. It is based on the leaf
      bombardment with tungsten microparticles with bound DNA using common air gun. The
      procedure did not require special equipment and source of driving gas. The
      transfection efficiency obtained by the newly developed procedure was close to
      100%, but this level dropped with the age of bombarded plants.

PMID- 21175256
TI  - Integrity of foot-and-mouth disease virions bound to the cells.
AB  - In this study, we examined the integrity of Foot-and-mouth disease virus (FMDV)
      particles during their binding to the surface of BHK-21 cells under physiological
      condition. For monitoring of the virus integrity we used blocking of the
      endocytosis with dynasore and cytochalasin D followed by RT-PCR for viral protein
      VP1 and the resistance of FMDV to the treatment of RNase A. Our results showed
      that integrin binding to VP1 did not cause a substantial conformational change in
      the viral capsid. Furthermore, treatment with RNase A showed no effect on the
      infectivity of intact as well as cell-bound virions. Our findings confirmed that
      FMDV entered the host cells in the form of intact virions.

PMID- 21175257
TI  - Effect of the route of foot-and-mouth disease virus infection of piglets on the
      course of disease.
AB  - Three different routes of Foot-and-mouth disease virus (FMDV) infection of
      piglets, namely intranasal (i.n.) through drops, intradermal (i.d.) into the
      foot, and intramuscular (i.m.) were compared regarding the onset and severity of
      the disease. The results showed that the i.d. injection of the virus resulted in
      the fastest onset of the disease. The i.m. injection led to a delayed onset, but
      the final effect was identical with i.d. injection. Moreover, the i.m. injection
      was simpler to perform and easier to evaluate. Therefore, the i.m. injection of
      piglets is recommended as the optimal infection route for evaluation of the FMDV
      vaccine potency.

PMID- 21175258
TI  - Comparison of PCRs for IE-1 and gB genes with ELISA of IgM antibodies for
      diagnosis of human cytomegalovirus disease.

PMID- 21175259
TI  - Tomato leaf curl New Delhi virus DNA A component and Cotton leaf curl Multan
      betasatellite can cause mild transient symptoms in cotton.

PMID- 21175260
TI  - Development of a real time RT-PCR with SYBR Green dye for the detection of
      several viruses from the bulbs and leaves of lily.

PMID- 21175262
TI  - Children in general practice: an exciting area for research. Reflections on the
      EGPRN meeting in Plovdiv, Bulgaria, May 2010.
AB  - The European General Practice Research Network organized an international
      research conference on 'Children in General Practice' in Plovdiv, Bulgaria, in
      May 2010. Two of the authors were keynote speakers at the workshop, tasked with
      summarizing the theme research presentations on each of the two days of the
      meeting. The theme of the meeting 'Children in General Practice' refers to the
      primary aim for timely and high quality health care for every child and the
      related general practitioners' activities. The meeting was an important event,
      especially for young doctors and investigators from different countries, because
      they were informed of good practices from other European countries in preventive
      work with children. All participants shared and learned a lot of good ideas
      beyond the standards and quality management. Examples of ideas for new research
      questions that emerged were to study differences in routine check-ups during
      childhood between European countries; to study the effectiveness of advices given
      by GPs to (parents of) obese children; and to study adverse events of medication
      in general practice. CONCLUSION: At a European level, the diversity of the ways
      health care systems deal with health problems in children is striking. We felt
      great enthusiasm to further develop this research area. Interested family doctors
      are invited to attend future conferences to develop collaborative research
      projects on this topic.

PMID- 21175261
TI  - Fluoxetine increases hippocampal neurogenesis and induces epigenetic factors but
      does not improve functional recovery after traumatic brain injury.
AB  - The selective serotonin reuptake inhibitor fluoxetine induces hippocampal
      neurogenesis, stimulates maturation and synaptic plasticity of adult hippocampal
      neurons, and reduces motor/sensory and memory impairments in several CNS
      disorders. In the setting of traumatic brain injury (TBI), its effects on
      neuroplasticity and function have yet to be thoroughly investigated. Here we
      examined the efficacy of fluoxetine after a moderate to severe TBI, produced by a
      controlled cortical impact. Three days after TBI or sham surgery, mice were
      treated with fluoxetine (10 mg/kg/d) or vehicle for 4 weeks. To evaluate the
      effects of fluoxetine on neuroplasticity, hippocampal neurogenesis and epigenetic
      modification were studied. Stereologic analysis of the dentate gyrus revealed a
      significant increase in doublecortin-positive cells in brain-injured animals
      treated with fluoxetine relative to controls, a finding consistent with enhanced
      hippocampal neurogenesis. Epigenetic modifications, including an increase in
      histone 3 acetylation and induction of methyl-CpG-binding protein, a
      transcription factor involved in DNA methylation, were likewise seen by
      immunohistochemistry and quantitative Western immunoblots, respectively, in brain
      injured animals treated with fluoxetine. To determine if fluoxetine improves
      neurological outcomes after TBI, gait function and spatial learning and memory
      were assessed by the CatWalk-assisted gait test and Barnes maze test,
      respectively. No differences in these parameters were seen between fluoxetine-
      and vehicle-treated animals. Thus while fluoxetine enhanced neuroplasticity in
      the hippocampus after TBI, its chronic administration did not restore locomotor
      function or ameliorate memory deficits.

PMID- 21175263
TI  - Ubiquitin ligase c-Cbl is involved in tamoxifen-induced apoptosis of MCF-7 cells
      by downregulating the survival signals.
AB  - BACKGROUND: Tamoxifen (TAM) is a nonsteroidal antiestrogen that has been widely
      used in the treatment of breast cancer through its anti-estrogen activity. Recent
      studies show that TAM is cytotoxic to both estrogen receptor (ER)-positive and ER
      negative cells via the induction of apoptosis. However, the molecular mechanisms
      of this effect are not well understood. In the present study, we investigated the
      roles of c-Src, ERK, AKT and c-Cbl ubiquitin ligases during TAM-induced apoptosis
      of MCF-7 cells. MATERIAL AND METHODS: MCF-7 cell proliferation and apoptosis were
      measured by 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)
      assay, and flow cytometry, respectively. c-Cbl expression, and the activity of c
      Src, ERK, AKT were assayed by Western blotting. Overexpression of the wild and
      the dominant-negative type of c-Cbl (70Z/Cbl) were achieved by transient
      transfection of plasmids encoding c-Cbl and 70Z/Cbl, respectively, and were
      confirmed by Western blotting. Statistical analysis was performed using the t
      test, and a p-value <0.05 was considered to be statistically significant.
      RESULTS: A high concentration of TAM (25 MUM) induced a time-dependent apoptosis
      of MCF-7 cells. ERK1/2 and AKT were activated during TAM-induced apoptosis. The
      ERK1/2 inhibitor PD98059, the PI3K/Akt inhibitor LY294002, and the c-Src
      inhibitor PP2 all enhanced TAM action. Moreover, the ubiquitin ligase c-Cbl was
      up-regulated during this process. Over-expression of c-Cbl significantly enhanced
      the apoptosis-inducing effects of TAM, while 70Z/Cbl suppressed the apoptosis
      inducing effects of TAM. Further investigation revealed that, overexpression of c
      Cbl significantly downregulated the c-Src protein levels and TAM-induced AKT
      activity. But 70Z/Cbl significantly upregulated TAM-induced ERK and AKT activity.
      CONCLUSIONS: This study demonstrates that c-Src, ERK, and AKT played a protective
      role during TAM-induced apoptosis, and that c-Cbl sensitized MCF-7 cells to TAM
      by modulating the expression of c-Src, and TAM-induced ERK and AKT activity.

PMID- 21175264
TI  - Single process for manufacturing spheres with a lipid base (HCO).
AB  - Pellets and spheres are manufactured in the pharmaceutical industry by various
      processes which are not always easily automated. In this paper, a 'single pot
      process' is described using rotary fluid bed granulation with lipid fillers. This
      technology is based on wet granulation of powder components, continuously
      suspended in a fluidized air with a tangentially sprayed liquid solution. After a
      previous work devoted to selection of matrix filler, this work focuses on lipid
      component: hydrogenated castor oil, used as matrix filler associated with
      theophylline as tracer. Spheres manufactured can be introduced either directly
      into a hard gelatine capsule or compressed as tablets. The influence of the
      formulation and process parameters on the sphere manufacture in terms of
      feasibility is studied with in vitro tests. Spraying time and weight of liquid
      sprayed are found to be the most relevant parameters that governed the final
      quality of the sphere.

PMID- 21175265
TI  - The mammalian orphan nuclear receptors: orphans as cellular guardians.
AB  - In classical endocrinology, receptors are molecules that bind a hormone or a
      ligand to transduce signal within a target cell. Later, however, many
      intracellular receptors have been discovered in mammals, which have not been
      shown to bind endogenous ligands and are now are referred as "orphan receptors."
      The orphan receptors share high degree of structural and functional homology with
      the classical nuclear receptors (NRs) and are now part of the NR superfamily and
      therefore referred as orphan nuclear receptors (ONRs). Interestingly, however,
      ONR members are not evolutionarily or functionally linked and they form a highly
      diverse group within the NR superfamily. In mammals, ONRs exhibit great
      functional diversity and majority of them are expressed in a tissue-specific
      fashion. In the past one decade, functional studies have revealed that they are
      mediators of multitude of crucial metabolic, developmental, reproductive, and
      immunological functions in mammals. Emerging studies also indicate the role of
      ONRs in the onset of several complex human diseases and hence they may be
      potential candidates for therapeutic drug targeting in the future.

PMID- 21175266
TI  - Hypoglycemia risk and glucose variability indices derived from routine self
      monitoring of blood glucose are related to laboratory measures of insulin
      sensitivity and epinephrine counterregulation.
AB  - BACKGROUND: the widely held assumptions that in type 1 diabetes glucose
      variability may correlate with insulin sensitivity and impaired epinephrine
      counterregulation have not been studied directly. Here we investigate possible
      relationships between outpatient measures of glucose variability and risk for
      hypoglycemia with physiological characteristics: insulin sensitivity and
      hypoglycemia counterregulation. METHODS: thirty-four subjects with type 1
      diabetes (14 women, 20 men; 37 +/- 2.1 years old; glycosylated hemoglobin
      [HbA1c], 7.6  +/-  0.21%) performed self-monitoring of blood glucose (SMBG) for a
      month, followed by an inpatient hyperinsulinemic euglycemic and hypoglycemic
      clamp. SMBG field data were used to calculate measures of glucose variability and
      risk of hypoglycemia, while the clamp procedure was used to evaluate insulin
      sensitivity and epinephrine response during induced hypoglycemia. Spearman
      partial correlations adjusted for age, duration of diabetes, body mass index,
      gender, and HbA1c were used to assess the relationship between the field indices
      of glucose variability and the physiological characteristics of diabetes.
      RESULTS: two glucose variability measures correlated positively (P < 0.01) with
      insulin sensitivity: the Average Daily Risk Range (ADRR) (rho = 0.5) and the
      Glycemic Lability Index (rho = 0.48). The Low Blood Glucose Index, a measure of
      the risk for hypoglycemia, and the ADRR correlated negatively with maximum
      epinephrine response during hypoglycemia: rho = -0.46, P < 0.01 and rho = -0.4, P
      = 0.03, respectively. CONCLUSIONS: higher insulin sensitivity and lower
      epinephrine response during hypoglycemia are related to increased glucose
      variability (as quantified by the ADRR), irrespective of HbA1c and other patient
      characteristics. Lower epinephrine relates to risk for hypoglycemia as well.

PMID- 21175267
TI  - Uncoupling protein 2 and 3 gene polymorphisms and their association with type 2
      diabetes in asian indians.
AB  - BACKGROUND: this study examined the association of -866G/A, Ala55Val, 45bpI/D,
      and -55C/T polymorphisms at the uncoupling protein (UCP) 3-2 loci with type 2
      diabetes in Asian Indians. METHODS: a case-control study was performed among
      1,406 unrelated subjects (487 with type 2 diabetes and 919 normal glucose
      tolerant [NGT]), chosen from the Chennai Urban Rural Epidemiology Study, an
      ongoing population-based study in Southern India. The polymorphisms were
      genotyped using polymerase chain reaction-restriction fragment length
      polymorphism and direct sequencing. Haplotype frequencies were estimated using an
      expectation-maximization algorithm. Linkage disequilibrium was estimated from the
      estimates of haplotypic frequencies. RESULTS: the genotype (P = 0.00006) and the
      allele (P = 0.00007) frequencies of Ala55Val of the UCP2 gene showed a
      significant protective effect against the development of type 2 diabetes. The
      odds ratios (adjusted for age, sex, and body mass index) for diabetes for
      individuals carrying Ala/Val was 0.72, and that for individuals carrying Val/Val
      was 0.37. Homeostasis insulin resistance model assessment and 2-h plasma glucose
      were significantly lower among Val-allele carriers compared to the Ala/Ala
      genotype within the NGT group. The genotype (P = 0.02) and the allele (P = 0.002)
      frequencies of -55C/T of the UCP3 gene showed a significant protective effect
      against the development of diabetes. The odds ratio for diabetes for individuals
      carrying CT was 0.79, and that for individuals carrying TT was 0.61. The
      haplotype analyses further confirmed the association of Ala55Val with diabetes,
      where the haplotypes carrying the Ala allele were significantly higher in the
      cases compared to controls. CONCLUSIONS: Ala55Val and -55C/T polymorphisms at the
      UCP3-2 loci are associated with a significantly reduced risk of developing type 2
      diabetes in Asian Indians.

PMID- 21175268
TI  - Effectiveness of sitagliptin in asian Indian patients with type 2 diabetes-an
      Indian tertiary diabetes care center experience.
AB  - BACKGROUND: this study reports on the effectiveness of sitagliptin in Asian
      Indian type 2 diabetes patients seen at a tertiary diabetes care center who had
      inadequate glycemic control with oral hypoglycemic agents either alone or in
      combination, compared to a group of patients who received insulin glargine.
      PATIENTS AND METHODS: patients with type 2 diabetes mellitus (n = 2,817) whose
      glycemia was not controlled adequately (glycated hemoglobin >6.5%) with oral
      hypoglycemic agents (either alone or in combination) received oral sitagliptin
      100 mg once daily in addition to existing therapy for a period of 24 weeks.
      Patients who received insulin glargine as add-on therapy (n = 2,743) served as
      the reference group. Data analysis included glycated hemoglobin, fasting plasma
      glucose, lipid profile, body weight, and the occurrence of hypoglycemia. RESULTS:
      significant reductions in glycated hemoglobin and fasting plasma glucose values
      were noted after 24 weeks of additional sitagliptin therapy that were comparable
      to those with insulin glargine. While sitagliptin addition resulted in a small
      weight loss (0.3 kg), insulin glargine addition resulted in a weight gain (0.7
      kg). The overall incidence of adverse experiences was low and generally mild in
      both groups. CONCLUSIONS: in a large group of Asian Indian type 2 diabetes
      patients seen at a tertiary diabetes center in whom glycemia was not controlled
      adequately by oral hypoglycemic agents (either alone or in combination), addition
      of sitagliptin helped to achieve glycemic control to a similar extent as insulin
      glargine but with a marginal weight advantage.

PMID- 21175269
TI  - Genetic variations in the FTO gene are associated with type 2 diabetes and
      obesity in south Indians (CURES-79).
AB  - AIM: the present study investigated the association of six variants-rs9940128,
      rs7193144, and rs8050136 (in intron 1), rs918031 and rs1588413 (in intron 8), and
      rs11076023 (3' untranslated region)-across three regulatory regions of the fat
      mass and obesity-associated (FTO) gene with obesity and type 2 diabetes mellitus
      (T2DM) in a South Indian population. METHODS: unrelated study subjects (n =
      1,852; 1,001 normal glucose-tolerant [NGT] controls and 851 cases [T2DM]) were
      randomly selected from the Chennai Urban Rural Epidemiological Study (CURES).
      Genotyping was done by the polymerase chain reaction-restriction fragment length
      polymorphism method, and 20% of samples were sequenced to validate the genotypes
      obtained. Haplotype analysis was also carried out. RESULTS: the three
      polymorphisms rs9940128 A/G, rs1588413 C/T, and rs11076023 A/T of the FTO gene
      were associated with T2DM in our study population. The rs8050136 C/A variant was
      associated with obesity, and its association with T2DM was also mediated through
      obesity. The rs1588413 C/T variant showed an association with obesity in the
      total study subjects, but when the NGT subjects alone were analyzed, the
      association with obesity was lost. The haplotype ACCTCT confers a lower risk of
      T2DM in this South Indian population. CONCLUSIONS: among South Indians, the
      rs9940128 A/G, rs11076023 A/T, and rs1588413 C/T variants of the FTO gene were
      associated with T2DM, whereas the rs8050136 C/A variant was associated with
      obesity.

PMID- 21175270
TI  - Factors associated with persistence and resumption of insulin pen use for
      patients with type 2 diabetes.
AB  - OBJECTIVE: this study assessed patient-related factors associated with
      persistence and resumption of using pens as insulin delivery devices. METHODS:
      patients (n = 549; 300 current pen users, 249 former pen users) were recruited
      from national panels to participate in computer-assisted telephone interviews.
      Measures included demographic characteristics, diabetes treatment and self-care
      factors, physician recommendation for pen use, perceptions of pen convenience,
      clinical efficacy, facilitation of self-care, cost, patient reasons for
      terminating pen use, and likelihood of resuming pen use among those who had
      terminated use. RESULTS: current and former pen users rated the pen higher (P <
      0.05) than vial and syringe on convenience, efficacy, facilitation of self-care,
      and cost, except for former users' ratings of cost. Current pen users rated pens
      higher (P < 0.05) than former users on all these measures. In addition to more
      positive pen perceptions, multivariate analysis showed that current users were
      more likely (P < 0.05) than former users to have received a pen recommendation
      from their physician, have better insurance coverage, and be working. Cost was
      the major reason reported for terminating pen use. Self-assessed likelihood of
      resuming pen use was higher (P < 0.05) among those with longer duration of pen
      use and more positive perceptions of pen cost and convenience. CONCLUSIONS:
      results suggest that physician recommendations of pen use, patient perceptions of
      pens, and cost and insurance coverage of pens may play an important role in
      persistence of pen use. Among former pen users, duration of pen use and
      perceptions of pens may be important factors in likelihood of patients' resuming
      pen use.

PMID- 21175271
TI  - The SWITCH study (sensing with insulin pump therapy to control HbA(1c)): design
      and methods of a randomized controlled crossover trial on sensor-augmented
      insulin pump efficacy in type 1 diabetes suboptimally controlled with pump
      therapy.
AB  - BACKGROUND: studies investigating the effect of real-time continuous glucose
      monitoring (CGM) combined with pump therapy on glycemic outcomes in type 1
      diabetes are increasing. Pump therapy is well established as a "gold standard"
      for insulin delivery, offering improvements over multiple daily insulin
      injections. However, there is still a proportion of subjects using continuous
      subcutaneous insulin infusion in whom goals for metabolic control are far from
      achieved or benefits of this type of insulin therapy are transient. The SWITCH
      (Sensing With Insulin pump Therapy to Control HbA(1c) [hemoglobin A1c]) study is
      a multicenter, randomized, controlled, crossover study to evaluate if adding CGM
      to experienced pump patients with suboptimal metabolic control will provide
      additional insight enabling clinical and therapeutic benefit. METHODS: subjects
      meeting the inclusion criteria were randomized to Sensor On or Sensor Off arms
      for 6 months, after a 1-month run-in period. Following a 4-month washout period,
      the subjects crossed over to the other study arm for 6 months. The primary end
      point was the between arm difference in HbA(1c) levels. Among others, additional
      end points include time spent in different glycemic ranges, percentage of
      patients with HbA(1c) <7%, number of hypoglycemic events, glucose variability
      parameters, safety outcomes, treatment satisfaction, and quality of life.
      RESULTS: recruitment occurred between January 2008 and February 2009. A total of
      153 patients were randomized. Study completion is anticipated in July 2010.
      CONCLUSIONS: the results will establish if adding CGM to existing, capable,
      insulin pump users can enable better metabolic control.

PMID- 21175272
TI  - Can one point-of-care glucose meter be used for all pediatric and adult hospital
      patients? Evaluation of three meters, including recently modified test strips.
AB  - BACKGROUND: within hospitals, bedside blood glucose measurements are widely used
      for investigating suspected hyper- or hypoglycemia, monitoring diabetes, and
      adjusting glucose-lowering medication. Numerous point-of-care glucose meters are
      available, but for large hospitals using the same meter in all settings has
      practical and economic advantages. This investigation sought to identify a meter
      that was accurate, precise, and free from interferences, making it suitable for
      use across all ages and diseases. METHODS: lithium-heparinized whole blood was
      analyzed, under various conditions, on the HemoCue Glucose 201 (Hemocue AB,
      Angelhom, Sweden), Accu-Chek Performa (Roche Diagnostics, Basel Switzerland)
      (using the newly reformulated maltose-insensitive strips), and Optium (Abbott
      Diabetes, Alameda, CA, USA) glucose meters and compared with plasma glucose
      measurements on the Vitros 5,1 FS analyzer (Ortho Clinical Diagnostics,
      Neckargemund, Germany). RESULTS: biases of 3.2%, -5.8%, and -8% were found with
      Accu-Chek, Optium, and HemoCue, respectively. Within-run imprecision was 2.5
      5.8%. Between-run imprecision was 3.1-6.8%, with the Accu-Chek performing best.
      All meters measured to 1.3 mmol/L with acceptable precision (coefficient of
      variation, <14%). Varying hematocrits between 0.2 and 0.7 L/L affected results of
      all meters. Interference at clinically relevant concentrations of galactose and
      possibly maltose was demonstrated with the Accu-Chek. CONCLUSIONS: all three
      meters are sufficiently accurate and precise for in-hospital use. Because of
      possible interference by galactosemia or high hematocrit, the Accu-Chek is not
      the safest option for neonatal use. Patients receiving high doses of maltose in
      therapeutic infusions may still be at risk of being falsely classified as
      euglycemic or hyperglycemic with the reformulated Accu-Chek strips, and clinical
      evaluation of these strips in patients receiving maltose-containing infusions is
      urgently needed.

PMID- 21175273
TI  - Effect of repaglinide versus glyburide on postprandial glucose and insulin values
      in elderly patients with type 2 diabetes.
AB  - BACKGROUND: studies in younger patients with diabetes have shown that insulin
      profiles are more physiologic and postprandial glucose levels are lower with
      repaglinide than with glyburide. We conducted this study to determine if the
      differences in insulin/glucose profiles between repaglinide and glyburide were
      similar or different in the elderly. METHODS: thirteen elderly patients with
      diabetes were given glyburide or repaglinide in randomized crossover design,
      followed by a meal tolerance test. Samples were taken at regular intervals to
      measure glucose and insulin values. RESULTS: the 0-30 min area under the curve
      (AUC) for insulin was higher (glyburide, 294  +/-  37 pM; repaglinide, 382  +/- 
      39 pM) (P < 0.01), and the 180-240 min AUC for insulin was lower (glyburide, 325 
      +/-  50 pM; repaglinide, 196 +/- 20 pM) (P < 0.01) with repaglinide. The 0-240
      min AUC for glucose was not different between treatments (glyburide, 7.4 +/-  0.5
      mM; repaglinide, 7.1 +/-  0.3 mM) (P = not significant). Five subjects treated
      with glyburide and no subjects treated with repaglinide required glucose from 180
      to 240 min (P < 0.05, Fisher's exact test). CONCLUSIONS: we conclude that
      repaglinide results in a more physiologic insulin profile and less frequent
      hypoglycemia than glyburide in the elderly.

PMID- 21175274
TI  - Titration of Insulin Glargine in Patients with Type 2 Diabetes Mellitus in Asia:
      Physician- Versus Patient-Led? Rationale of the Asian Treat to Target Lantus
      Study (ATLAS).
AB  - OBJECTIVE: the AT-LANTUS Study demonstrated that a simple subject-administered
      titration algorithm significantly improved glycemic control with a low incidence
      of severe hypoglycemia compared with a physician-managed titration. However, in
      the AT-LANTUS Study Asian patients were under-represented, and more than 70% of
      the patients were already treated with insulin. The Asian Treat to Target Lantus
      Study (ATLAS) will compare the effectiveness of a patient- versus physician-led
      initiation of insulin glargine-based basal management in the specific setting of
      Asia and Russia (as is routinely used in Western countries). This report presents
      the study design of ATLAS. METHODS: subjects are 40-75 years old (body mass index
      >= 20 and <= 40 kg/m(2)) with type 2 diabetes mellitus (T2DM) of >2 years in
      duration, suboptimally controlled (hemoglobin A1c [HbA1c] >= 7.0% and <= 11%)
      with stable doses of two oral antidiabetes drugs (OADs) (sulfonylureas,
      biguanides, alpha-glucosidase inhibitors, dipeptidyl peptidase-IV inhibitors, and
      glinides) for more than 3 months, and not using insulin. The subjects will be
      randomized to either the patient-led or the physician-led titration arm, where
      the insulin dose will be adjusted to achieve a target fasting plasma glucose
      (FPG) value of 110 mg/dL (6.1 mmol/L). STUDY OUTCOMES: the primary outcome will
      be change in mean HbA1c at 6 months from baseline. The analysis plan prespecifies
      a hierarchical testing procedure for the primary outcome. If noninferiority is
      achieved using a 0.3% HbA1c boundary, we will go on to undertake a test for
      superiority. Secondary outcomes will also include number of patients reaching
      American Diabetes Association target HbA1c with or without hypoglycemia and
      analysis of FPG profiles in the two groups. CONCLUSIONS: ATLAS will provide
      information on the relative safety and efficacy of a patient- versus physician
      led titration strategy for insulin glargine-based basal insulin initiation in
      patients who are not controlled with two OADs in Asia and Russia. The results of
      the study may guide policymakers to translate data into clinical practice.

PMID- 21175275
TI  - Impact of psychiatric comorbidity on mortality in veterans with type 2 diabetes.
AB  - BACKGROUND: particular psychiatric disorders, such as depression, have a
      significant and negative effect on diabetes outcomes. However, we know very
      little about the impact of other psychiatric disorders, and of the effect of
      multiple psychiatric comorbidities, on the clinical course of diabetes. As such,
      the present study examined the impact of a wide range of psychiatric
      comorbidities on all-cause mortality in individuals with type 2 diabetes.
      METHODS: retrospective follow-up was conducted of 15,065 veterans with type 2
      diabetes enrolled in hospital care between 1997 and 2006. Clinical diagnoses from
      patient records were used to construct four psychiatric disorder scales:
      internalizing (i.e., depression and anxiety); externalizing (i.e., alcohol and
      drug abuse); psychotic; and bipolar. Longitudinal relationships were examined
      between these scales and mortality using Cox regression. RESULTS: only
      externalizing disorders were significantly associated with mortality: hazard
      ratio = 1.22 (95% confidence interval = 1.02-1.47). In other words, each
      additional diagnosed externalizing disorder increased an individual's chance of
      dying over the follow-up period by 22%. This association remained significant
      when demographics and medical comorbidities were statistically controlled, but
      was rendered nonsignificant when medication adherence was introduced to the
      regression model. CONCLUSIONS: the results provide evidence that among
      individuals with diabetes, alcohol and drug abuse/dependence have a significant
      impact on mortality. This increased risk of mortality may have been due to the
      association between psychiatric disorders and adherence to antidiabetes
      medications observed in the present study. Individuals with co-occurring diabetes
      and alcohol or drug abuse should be targeted for intensive interventions given
      their acute increased risk of mortality.

PMID- 21175276
TI  - Glucose and insulin administration while maintaining normoglycemia during cardiac
      surgery using a computer-assisted algorithm.
AB  - BACKGROUND: applying the principles of the hyperinsulinemic-normoglycemic clamp
      technique we have introduced glucose and insulin administration while maintaining
      normoglycemia (GIN therapy) to surgical patients. The objective of this study was
      to evaluate a novel computer software (GIN Computer Software [GINCS]) program
      using an algorithm based on the original clamp equation and modified for its use
      during cardiac surgery. METHODS: thirty-six patients without diabetes undergoing
      elective cardiac surgery were randomly assigned to manually controlled or
      computer-guided GIN therapy. In both groups insulin was administered at 5
      mU/kg/min during surgery. Simultaneously, 20% dextrose was infused at a rate
      adjusted to maintain blood glucose (BG) between 4.0 and 6.0 mmol/L. The
      adjustments were made either following an algorithm based on our previous GIN
      experience or suggestions made by the software program. The primary outcome was
      the achievement of target glycemia. RESULTS: normoglycemia was achieved in both
      groups as reflected by mean BG concentrations of 5.0 +/- 0.5 mmol/L and 5.1 +/-
      0.2 mmol/L. Mean sampling intervals were longer in the GINCS group than in the
      manual group (21.5  +/- 1.9 vs. 14.2 +/- 2.2 min, P < 0.001). The GINCS therapy
      was associated with a greater percentage of BG measurements within target (manual
      group, before cardiopulmonary bypass [CPB] 79.7%, during CPB 68.1%, and after CPB
      69.1%; GINCS group, before CPB 94.1%, during CPB 92.4%, and after CPB 97.7%; P <
      0.001). No hypoglycemia was observed. CONCLUSIONS: the use of a computer-guided
      GIN protocol in patients without diabetes undergoing open heart surgery provided
      excellent and safe glycemic control.

PMID- 21175277
TI  - Are glucose readings sufficient to adjust insulin dosage?
AB  - AIMS/HYPOTHESIS: insulin therapy is effective predominantly when dosage is
      frequently adjusted. However, a controversy surrounds the pertinent clinical
      parameters required to make effective and safe frequent dosage adjustments. We
      hypothesize that glucose readings are sufficient to adjust insulin dosage
      provided that dosage is adjusted every 1-4 weeks. METHODS: to test the
      hypothesis, we generated several algorithms implemented in software to process
      glucose readings and recommend insulin dosage adjustments. A post hoc analysis
      was made on 630 log sheets (2,520 insulin dosage adjustments) from 26 older
      adults with suboptimally controlled type 2 diabetes. The subjects were followed
      for a year and treated with intensive insulin therapy that was titrated every 1-4
      weeks by a trained study team. More than 88% of subjects attained the treatment
      goal (hemoglobin A1c <7%) without excessive hypoglycemia. Glucose readings from
      each log sheet were used as an input to the software, and its recommendations for
      insulin dosage adjustments were compared to the original ones made by the study
      team. While the study team could have been exposed to multiple clinical
      parameters, the software relied solely on glucose readings. RESULTS: the software
      recommendations for dosage adjustments were clinically equivalent to the original
      study team's recommendations in more than 95% of the cases, unrelated to
      patients' insulin sensitivity. The remaining 4.4% (n = 111) were thoroughly
      examined, yet we did not find any recommendations suggested by the software to be
      unsafe or unreasonable. CONCLUSIONS/INTERPRETATION: glucose readings are
      sufficient to effectively adjust insulin dosage provided that adjustments are
      made every 1-4 weeks. Therefore, dedicated software can help adjusting insulin
      dosage between clinic visits.

PMID- 21175278
TI  - Visual pursuit in the severe disorder of consciousness.
AB  - Visual pursuit is a key descriptor of the minimally conscious state (above 80% of
      cases). It is also observable in about 20% of subjects in vegetative state. Its
      reappearance after severe brain damage anticipates a favorable outcome, with
      recovery of consciousness in 73% of subjects (45% in the absence of it). We
      considered retrospectively 395 subjects in vegetative state because of traumatic
      (63%), massive acute vascular (30%), or diffuse anoxic-hypoxic (7%) brain damage
      consecutively admitted to one dedicated unit during the years 1998-2008. Visual
      tracking was observed in 290 subjects (73.4%) and was already detectable within
      50 days from brain injury in about 60% of post-traumatic or vascular subjects and
      21% of anoxic-hypoxic patients. After 230 days of follow-up or more, it was
      observed in 89% and 88% of post-traumatic and vascular subjects and in 67% of
      anoxic-hypoxic patients. Rating with the Glasgow Outcome Scale (GOS) was better
      in those subjects with recovered visual tracking and inversely correlated with
      the time of reappearance in post-traumatic and vascular subjects; also the
      subjects with late recovery of eye tracking (230 days or more) had better GOS
      outcome than those without it. The observation of visual tracking reappearing in
      subjects in vegetative state would reflect recuperation of the brainstem-cortical
      interaction and overall brain functional organization that are thought to sustain
      consciousness and are interfered with by the "functional disconnection,"
      resulting in the vegetative state.

PMID- 21175279
TI  - Does the regeneration of hippocampal neurons offer hope for the treatment of
      cognitive deficits?

PMID- 21175284
TI  - Conference Scene: Induced pluripotent cells: a new path for regenerative
      medicine. 7 October 2010, BioPark, Welwyn Garden City, Hertfordshire, UK.
AB  - Embryonic stem cells and induced pluripotent stem (iPS) cells, which are
      embryonic stem-like cells derived from adult tissues, have the broadest
      differentiation potential. These cells are unique in their ability to self-renew,
      to be maintained in an undifferentiated state for long periods of culturing and
      to give rise to many different cell lineages including germ-line cells. They
      therefore represent an invaluable tool for facilitating research towards the
      realization of regenerative medicine. The recent developments in embryonic stem
      cell and iPS cell technology have allowed human cell models to be developed that
      will hopefully provide novel platforms for disease analysis not only at the basic
      science level, but also for drug discovery and screening, and other clinical
      applications. This 1-day conference, chaired by Professor Peter Andrews from the
      University of Sheffield, UK, and Dr Chris Denning from the University of
      Nottingham, UK, focused on generation of iPS cells, their differentiation into
      specific fates and applications to disease modeling. It consisted of 11 talks by
      UK-based and international researchers, and three posters; Ms Azra Fatima from
      Cologne University, Germany, won the competition for her poster on the derivation
      of iPS cells from a patient with arrhythmogenic right ventricular cardiomyopathy.

PMID- 21175285
TI  - Company profile: Athersys.
AB  - Athersys (Nasdaq: ATHX) is a biopharmaceutical company engaged in the discovery
      and development of novel therapies designed to treat significant unmet medical
      needs. The company is heavily focused on the regenerative medicine area, with
      multiple clinical and preclinical stage programs. The most advanced programs at
      the company are focused on the development of MultiStem(r), a clinical stage
      allogeneic stem cell therapy that has demonstrated potential for treating a range
      of conditions and is believed to have widespread application in the field of
      regenerative medicine. The company has internal programs applying MultiStem
      across multiple therapeutic areas including cardiovascular, neurological, immune
      dysfunction and other disease areas, and partnered programs with Pfizer (applying
      MultiStem to treat inflammatory bowel disease) and Angiotech Pharmaceuticals
      (acute myocardial infarction). Athersys has a broad network of collaborative
      relationships with leading research and clinical institutions and is committed to
      developing a pipeline of novel 'best-in-class' medicines.

PMID- 21175286
TI  - Safety of autologous bone marrow mononuclear cell transplantation in patients
      with nonacute ischemic stroke.
AB  - AIMS: To assess the safety and feasibility of intra-arterial transplantation of
      autologous bone marrow mononuclear cells in patients with middle cerebral artery
      ischemic stroke within 90 days of symptom onset. PATIENTS & METHODS: Six patients
      were included in the study, and they received 1-5 * 10(8) bone marrow mononuclear
      cell and were evaluated using blood tests, neurological and imaging examination
      before treatment, and 1, 3, 7, 30, 60, 90, 120 and 180 days after
      transplantation. Scintigraphies were carried out 2 and 24 h after the procedure
      to analyze the biodistribution of labeled cells. Electroencephalogram was
      conducted within 7 days after transplantation. RESULTS: No patients exhibited any
      complication or adverse events during the procedure. There was no worsening in
      the neurological scales until the end of the follow-up. CONCLUSION: Intra
      arterial bone marrow mononuclear cell transplantation is feasible and safe in
      patients with nonacute ischemic strokes of the middle cerebral artery. Further
      studies are required to evaluate the efficacy of this therapy.

PMID- 21175287
TI  - Efficient generation and cryopreservation of cardiomyocytes derived from human
      embryonic stem cells.
AB  - AIM: Human embryonic stem cells (hESCs) represent a novel cell source to treat
      diseases such as heart failure and for use in drug screening. In this study, we
      aim to promote efficient generation of cardiomyocytes from hESCs by combining the
      current optimal techniques of controlled growth of undifferentiated cells and
      specific induction for cardiac differentiation. We also aim to examine whether
      these methods are scalable and whether the differentiated cells can be
      cryopreserved. METHODS & RESULTS: hESCs were maintained without conditioned
      medium or feeders and were sequentially treated with activin A and bone
      morphogenetic protein-4 in a serum-free medium. This led to differentiation into
      cell populations containing high percentages of cardiomyocytes. The
      differentiated cells expressed appropriate cardiomyocyte markers and maintained
      contractility in culture, and the majority of the cells displayed working chamber
      (atrial and ventricular) type electrophysiological properties. In addition, the
      cell growth and differentiation process was adaptable to large culture formats.
      Moreover, the cardiomyocytes survived following cryopreservation, and viable
      cardiac grafts were detected after transplantation of cryopreserved cells into
      rat hearts following myocardial infarctions. CONCLUSION: These results
      demonstrate that cardiomyocytes of high quality can be efficiently generated and
      cryopreserved using hESCs maintained in serum-free medium, a step forward towards
      the application of these cells to human clinical use or drug discovery.

PMID- 21175288
TI  - Effect of platelet-rich plasma on dental stem cells derived from human impacted
      third molars.
AB  - AIM: Platelet-rich plasma (PRP) is fabricated from autologous blood and
      extensively used to promote soft and hard tissue healing. In the dental field,
      autologous PRP is widely used combined with dental implant installation and bone
      graft. This study will evaluate the biologic effect of PRP on the proliferation
      and the differentiation of human dental stem cells, and find the key cytokines
      inducing these effects to estimate the clinical feasibility of PRP for dental
      tissue engineering. MATERIALS & METHODS: Venous blood was obtained from four
      individuals and each PRP was fabricated. The human dental stem cells were
      obtained from the periodontal ligament (PDL) and dental pulp of the surgically
      extracted human third molars and expanded in vitro. Immunocytochemical staining
      and flow cytometry with STRO-1 and CD146 confirmed existence of mesenchymal stem
      cells in the PDL and dental pulp. The effect of PRP on the proliferation of PDL
      stem cells (PDLSCs) and dental pulp stem cells (DPSCs) was assessed by colony
      forming ability measurement, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide assay and bromodeoxyuridine incorporation assay. Alkaline phosphatase
      activity and calcium deposit were measured to evaluate the mineralization effect
      of PRP PDLSCs and DPSCs. Alizarin red S staining was used to detect mineral
      nodules. Odontogenic and osteogenic gene expressions were evaluated in the PRP
      treated PDLSCs and DPSCs by real-time quantitative PCR. A protein array was
      performed to detect the key cytokines that have an important role in the tissue
      regenerative effect of PRP. RESULTS: Flow cytometry cell sorting showed that the
      cells from human PDL and dental pulp contained mesenchymal stem cell populations.
      Colony-forming ability and cellular proliferation of the dental stem cells were
      increased at 0.5 and 1% PRP concentration but decreased at 5% concentration. Long
      term treatment with 1% PRP enhanced proliferation of the human dental stem cells
      PDLSCs and DPSCs by 120 h and showed the most significant enhancement at 96 h.
      PRP also promoted mineralization differentiation of the two kinds of dental stem
      cells as shown by measurement of alkaline phosphatase activity and calcium
      deposit under mineralization conditioned media. Increased formation of mineral
      nodules stained with alizarin red was observed in both PDLSCs and DPSCs after
      treatment with 1% PRP. Real-time quantitative PCR showed higher odontogenic and
      osteogenic gene expressions in PRP-treated PDLSCs and DPSCs. RANTES/CCL5 and ICAM
      1 were the two key cytokines that were detected in human cytokine array with PRP.
      CONCLUSION: The appropriate concentration of the PRP treatment enhanced
      proliferation and mineralization differentiation of human dental stem cells.
      RANTES/CCL5 and ICAM-1 might play an important role in PRP-induced tissue
      regeneration but further study is needed to investigate the whole mechanism.

PMID- 21175289
TI  - Engineered cartilage using primary chondrocytes cultured in a porous cartilage
      derived matrix.
AB  - AIM: To investigate the cell growth, matrix accumulation and mechanical
      properties of neocartilage formed by human or porcine articular chondrocytes on a
      porous, porcine cartilage-derived matrix (CDM) for use in cartilage tissue
      engineering. MATERIALS & METHODS: We examined the physical properties, cell
      infiltration and matrix accumulation in different formulations of CDM and
      selected a CDM made of homogenized cartilage slurry as an appropriate scaffold
      for long-term culture of human and porcine articular chondrocytes. RESULTS: The
      CDM scaffold supported growth and proliferation of both human and porcine
      chondrocytes. Histology and immunohistochemistry showed abundant cartilage
      specific macromolecule deposition at day 28. Human chondrocytes migrated
      throughout the CDM, showing a relatively homogeneous distribution of new tissue
      accumulation, whereas porcine chondrocytes tended to form a proteoglycan-rich
      layer primarily on the surfaces of the scaffold. Human chondrocyte-seeded
      scaffolds had a significantly lower aggregate modulus and hydraulic permeability
      at day 28. CONCLUSIONS: These data show that a scaffold derived from native
      porcine articular cartilage can support neocartilage formation in the absence of
      exogenous growth factors. The overall characteristics and properties of the
      constructs depend on factors such as the concentration of CDM used, the porosity
      of the scaffold, and the species of chondrocytes.

PMID- 21175291
TI  - Tissue engineering approaches for regenerative dentistry.
AB  - Although teeth can withstand enormous abrasive forces, they are susceptible to
      damage due to trauma, acids and bacterial attack. Conventional treatment relies
      on synthetic materials to fill defects and replace whole teeth, but these remain
      substitutes and cannot restore the tissues' physiological architecture and
      function. With the isolation of postnatal stem cells from various sources in the
      oral cavity and the development of smart materials for cell and growth factor
      delivery, possibilities for alternative, biology-based treatments arise.
      Interdisciplinary approaches are needed to move from replacement to regeneration,
      involving clinicians as well as biologists, stem cell researchers and material
      scientists. First, in order to provide an appreciation for the complexity of the
      tooth as a whole, its components and surrounding structures will be described.
      Next, the basic principles of tooth development will be presented, which can be
      applied to recreate signaling events and utilize them to build whole teeth. For
      the regeneration of individual tooth structures, the classical tissue engineering
      triad can be utilized, using dental stem cells, scaffold materials and relevant
      growth and differentiation factors. Recent successful engineering initiatives on
      whole teeth as well as on specific tissues such as enamel, the dentin-pulp
      complex or periodontal ligament will be discussed. In projecting future research
      directions, we conclude with a brief discussion of key components necessary to
      develop effective strategies for dental tissue engineering, which might enable us
      to implement novel regenerative strategies in clinical practice in the near
      future.

PMID- 21175292
TI  - Stem cell policy in the Obama age: UK and US perspectives.
AB  - In this article, we compare two different approaches to establishing stem cell
      policy: a defined policy (the UK) and a changing policy (the US). The UK has a
      clear and precise policy, agreed upon and supported by lawmakers, scientists and
      the public. By contrast, US federal policy is continuously being updated based on
      balancing political ideologies and advances in science, and it only regulates
      federal funding. By investigating these contrasting policy approaches, we hope to
      demonstrate the impact of policy on stem cell research and public opinion.

PMID- 21175290
TI  - Musculoskeletal tissue engineering with human umbilical cord mesenchymal stromal
      cells.
AB  - Multipotent mesenchymal stromal cells (MSCs) hold tremendous promise for tissue
      engineering and regenerative medicine, yet with so many sources of MSCs, what are
      the primary criteria for selecting leading candidates? Ideally, the cells will be
      multipotent, inexpensive, lack donor site morbidity, donor materials should be
      readily available in large numbers, immunocompatible, politically benign and
      expandable in vitro for several passages. Bone marrow MSCs do not meet all of
      these criteria and neither do embryonic stem cells. However, a promising new cell
      source is emerging in tissue engineering that appears to meet these criteria:
      MSCs derived from Wharton's jelly of umbilical cord MSCs. Exposed to appropriate
      conditions, umbilical cord MSCs can differentiate in vitro along several cell
      lineages such as the chondrocyte, osteoblast, adipocyte, myocyte, neuronal,
      pancreatic or hepatocyte lineages. In animal models, umbilical cord MSCs have
      demonstrated in vivo differentiation ability and promising immunocompatibility
      with host organs/tissues, even in xenotransplantation. In this article, we
      address their cellular characteristics, multipotent differentiation ability and
      potential for tissue engineering with an emphasis on musculoskeletal tissue
      engineering.

PMID- 21175294
TI  - Intrathecal injection of helper-dependent adenoviral vectors results in long-term
      transgene expression in neuroependymal cells and neurons.
AB  - Helper-dependent adenoviral (HDAd) vectors are devoid of all viral genes and
      result in long-term transgene expression in the absence of chronic toxicity.
      Because of their ability to infect post-mitotic cells, including cells of the
      central nervous system, HDAd vectors are particularly attractive for brain
      directed gene therapy. In this study, we show that intrathecal injection of HDAd
      results in extensive transduction of ependymal cells and sustained expression of
      the transgene up to 1 year post-administration. We also demonstrate, for the
      first time, the ability of HDAd injected by this route of delivery to transduce
      neuronal cells. The transduced neuroepithelial cells can be potentially used to
      secrete therapeutic proteins into the cerebrospinal fluid and provide them via
      cross-correction to nontransduced cells. Targeting of neuronal cells and long
      term transgene expression make this approach attractive for the treatment of
      several neurologic diseases.

PMID- 21175295
TI  - Pigment epithelium-derived factor gene therapy targeting retinal ganglion cell
      injuries: neuroprotection against loss of function in two animal models.
AB  - Lentiviral vectors are promising tools for the treatment of chronic retinal
      diseases including glaucoma, as they enable stable transgene expression. We
      examined whether simian immunodeficiency virus (SIV)-based lentiviral vector
      mediated retinal gene transfer of human pigment epithelium-derived factor (hPEDF)
      can rescue rat retinal ganglion cell injury. Gene transfer was achieved through
      subretinal injection of an SIV vector expressing human PEDF (SIV-hPEDF) into the
      eyes of 4-week-old Wistar rats. Two weeks after gene transfer, retinal ganglion
      cells were damaged by transient ocular hypertension stress (110 mmHg, 60 min) and
      N-methyl-d-aspartic acid (NMDA) intravitreal injection. One week after damage,
      retrograde labeling with 4',6-diamidino-2-phenylindole (DAPI) was done to count
      the retinal ganglion cells that survived, and eyes were enucleated and processed
      for morphometric analysis. Electroretinographic (ERG) assessment was also done.
      The density of DAPI-positive retinal ganglion cells in retinal flat-mounts was
      significantly higher in SIV-hPEDF-treated rats compared with control groups, in
      both transient ocular hypertension and NMDA-induced models. Pattern ERG
      examination demonstrated higher amplitude in SIV-hPEDF-treated rats, indicating
      the functional rescue of retinal ganglion cells. These findings show that
      neuroprotective gene therapy using hPEDF can protect against retinal ganglion
      cell death, and support the potential feasibility of neuroprotective therapy for
      intractable glaucoma.

PMID- 21175296
TI  - The multiple-dosing pharmacokinetics of artemether, artesunate, and their
      metabolite dihydroartemisinin in rats.
AB  - 1. The present study was designed to investigate the multiple-dosing
      pharmacokinetics of antimalarial drugs artemether (ARM), artesunate (ARS), and
      their metabolite dihydroartemisinin (DHA) in rats. 2. Rats were randomized into
      four groups. Two groups of rats received oral doses of ARM or ARS once daily for
      five consecutive days. And another two groups of rats were given a single oral
      dose of ARM or ARS. Plasma samples were analysed for artemisinin drugs and their
      active metabolite DHA, using a validated liquid chromatography/tandem mass
      spectrometric (LC/MS/MS) method. 3. ARM and ARS could be biotransformed to
      metabolite DHA almost immediately after oral administration to rats. The area
      under the plasma concentration-time curve (AUC(0-t)) of ARM after 5-day oral
      doses significantly decreased from 50.3 to 23.4 ng * h/mL (P < 0.05), and oral
      clearance (CL/F) of ARM increased from 10.5 to 27.2 L/min/kg (P < 0.05). The
      AUC(0-t) of its metabolite DHA of ARM significantly decreased from 42.1 to 16.4
      ng * h/mL (P < 0.05), and its CL/F increased from 11.7 to 33.4 L/min/kg (P <
      0.05). The 5-day oral doses of ARS did not result in significant changes (P >
      0.05) in pharmacokinetic parameters of ARS, whereas its metabolite DHA exhibited
      lower AUC (P = 0.05), compared with that obtained after a single oral
      administration. 4. The results showed ARM and its metabolite DHA exhibited time
      dependent pharmacokinetic characteristics with decreased plasma drug level after
      five consecutive days of oral administration to rats, whereas ARS and its
      metabolite DHA did not show similar characteristics.

PMID- 21175297
TI  - A substance P antagonist reduces axonal injury and improves neurologic outcome
      when administered up to 12 hours after traumatic brain injury.
AB  - Previous studies have demonstrated that the compound N-acetyl-L-tryptophan (NAT)
      reduces brain edema and improves functional outcome following traumatic brain
      injury (TBI). In this study we examined whether this effect was mediated via the
      neurokinin-1 receptor, and whether there was an effect on axonal injury. We also
      explored whether the compound was effective, even when administered at delayed
      time points. Male Sprague-Dawley rats were subject to acceleration-induced,
      diffuse TBI and administered NAT, its inactive D-enantiomer, or saline vehicle.
      In contrast to NAT (2.5 mg/kg), the inactive D-enantiomer was ineffective at
      improving rotarod motor performance after TBI. NAT also improved cognitive
      outcome as assessed by the Morris water maze and novel object recognition tests,
      and reduced axonal injury at 5 and 24 h after TBI as assessed by amyloid
      precursor protein immunohistochemistry. However, efficacy of the membrane
      impermeable NAT was limited to administration within 5 h, whereas administration
      of a form of NAT, L-732,138 (47 mg/kg), in which a trifluoromethyl benzyl ester
      group has been added, making it highly lipid soluble and able to cross the intact
      blood-brain barrier, significantly improved motor outcome, even when
      administration was delayed by as much as 12 h. We conclude that the
      neuroprotective effects of NAT are receptor-mediated, and that administration of
      the membrane-permeable form of the compound can be effective even up to 12 h
      after TBI.

PMID- 21175298
TI  - Pharmacotoxicology of monocyte-macrophage nanoformulated antiretroviral drug
      uptake and carriage.
AB  - Limitations inherent to antiretroviral therapy (ART) in its pharmacokinetic
      properties remain despite over 15 years of broad use. Our laboratory has
      pioneered a means to improve ART delivery through monocyte-macrophage carriage of
      nanoformulated drug-encapsulated particles (nanoART). To this end, our prior
      works sought to optimize nanoART size, charge, and physical properties for cell
      uptake and antiretroviral activities. To test the functional consequences of
      indinavir, ritonavir, and efavirenz formulations we investigated relationships
      between human monocyte and macrophage cytotoxicities and nanoART dose, size,
      surfactant, and preparation. Wet-milled particles were more cytotoxic to
      monocytes-macrophages than those prepared by homogenization; with concurrent
      induction of tumor necrosis factor-alpha. Interestingly, pure suspensions of
      indinavir and ritonavir at 0.5 mM, and efavirenz at 0.1 mM and 0.5 mM also proved
      cytotoxic. Individual surfactants and formulated fluconazole neither affected
      cell function or viability. Although nanoART did not alter brain tight junction
      proteins ZO-2 and occludin, 0. 5mM ritonavir formulations did alter brain
      transendothelial electric resistance. These results underscore the potential
      importance of evaluating the physicochemical and functional properties of nanoART
      before human evaluations.

PMID- 21175299
TI  - Brain microvessel endothelial cells responses to gold nanoparticles: In vitro pro
      inflammatory mediators and permeability.
AB  - This report examined blood-brain barrier (BBB) related proinflammatory mediators
      and permeability changes in response to various sized gold nanoparticles (Au-NPs)
      (3, 5, 7, 10, 30 and 60 nm) in vitro using primary rat brain microvessel
      endothelial cells (rBMEC). The Au-NPs were characterized by transmission electron
      microscopy (TEM), dynamic light scattering (DLS) and laser Doppler velocimetry
      (LDV). The accumulation of Au-NPs was determined spectrophotometrically. The
      rBMEC cytotoxicity of Au-NPs was evaluated by cell proliferation assay (XTT)
      (concentration range 0.24-15.63 MUg/cm2, for 24 h). The time-dependent changes
      (0, 2, 4 and 8 h) of several proinflammatory mediators (IL-1beta, IL-2, TNFalpha
      and PGE2) were evaluated by ELISA. The smaller Au-NPs (3-7 nm) showed higher
      rBMEC accumulation compared to larger Au-NPs (10-60 nm), while only moderate
      decreased cell viability was observed with small Au-NPs (3 nm) at high
      concentrations (>= 7.8 MUg/cm2). Even though slight changes in cell viability
      were observed with small Au-NPs, the basal levels of the various proinflammatory
      mediators remained unchanged with all treatments except LPS (positive control).
      rBMEC morphology appeared unaffected 24 h after exposure to Au-NPs with only mild
      changes in fluorescein permeability indicating BBB integrity was unaltered.
      Together, these data suggest the responses of the cerebral microvasculature to Au
      NPs have a significant relationship with the Au-NPs unique size-dependent
      physiochemical properties.

PMID- 21175301
TI  - Quality evaluation of rice bran protein isolate-based weaning food for
      preschoolers.
AB  - Agro-industrial waste 'rice bran' was stabilized and the extracted protein
      isolates were used as ingredients to make nutritive complimentary food for the
      growing infants. The formulation processed through drum drying and the starchy
      ingredients were pregelatinized to reduce bulk in the prepared meal and
      facilitate spoon-feeding. The formulations had uniform texture, light golden
      color and good paste consistency. Nutrient composition was good enough to meet
      standards for supplementary infant foods. Caloric value remained up to 416
      kcal/100 g with spoonable viscosity and 80.90-84.45% in vitro digestibility. A
      single meal could substantially contribute to the daily essential amino acid
      requirement. The formulation had good acceptability during a short-term infant
      feeding trial. The present study can provide practical guideline for
      manufacturers as well as the nutritionist for the use of an economical and
      nutritive formulation for young children.

PMID- 21175300
TI  - Significant associations of age, menopausal status and lifestyle factors with
      visceral adiposity in African-American and European-American women.
AB  - BACKGROUND: Elevated visceral adiposity is strongly predictive of cardiometabolic
      disease, but, due to the high cost of biomedical imaging, assessment of factors
      contributing to normal variation in visceral (VAT) and subcutaneous (SAT) adipose
      tissue partitioning in large cohorts of healthy individuals are few, particularly
      in ethnic and racial minority populations. OBJECTIVE: To describe age, menopausal
      status, smoking and physical activity differences in VAT and abdominal
      subcutaneous adipose tissue (ASAT) mass in African-American (AA) and European
      American (EA) women. METHODS: Magnetic resonance imaging measures of VAT and ASAT
      mass and VAT% (VAT/VAT+ASAT, %) were obtained from a cross-sectional sample of
      617 EA and 111 AA non-diabetic women aged 18-80 years. Multivariate linear
      regression was used to test independent effects of the covariates. RESULTS: VAT
      and VAT% were higher in EA than AA women (p < 0.01). Differences in VAT, ASAT and
      VAT% across age groups began in early adulthood in both ethnic groups, but the
      association of age with VAT% was stronger in EA women (p for interaction = 0.03).
      Current smokers had higher VAT and VAT% (p < 0.01) and lower TBF than non
      smokers. Frequent participation in sports activities was associated with ~30%
      lower VAT in older (>55 years) as well as younger ( < 40 years) women (p <
      0.0001). CONCLUSION: Greater allocation of abdominal adipose tissue into the
      visceral compartment occurs in EA than AA women and in older than younger women.
      Avoidance of cigarette smoking and frequent participation in sports activities
      may partially counteract this deleterious phenomenon of ageing.

PMID- 21175302
TI  - Revised birth centiles for weight, length and head circumference in the UK-WHO
      growth charts.
AB  - BACKGROUND: The adoption in May 2009 by the UK of the WHO 2006 standard
      necessitated the provision of UK-based birth centiles for pre-term infants. The
      pre-existing British 1990 reference birth centiles, used in the UK since 1995,
      had been biased by the inclusion of post-natal data. AIM: To describe the
      construction of new UK birth centiles for weight, length and head circumference,
      based on British 1990 reference data, but excluding post-natal data. SUBJECTS AND
      METHODS: Birth data from the five original studies, collected between 1983-1993,
      were pooled and analysed by the LMS method, for the sexes separately. In
      addition, sex-specific composite centiles were constructed for infants born at
      term (37-42 completed weeks). RESULTS: The birth data included 9443 weights, 985
      lengths and 1841 head circumferences, covering 23-44 weeks gestation. The
      analysis provided LMS tables defining reference centiles for weight and head
      circumference from 23-42 weeks and for length from 26-42 weeks. The term centiles
      are for use at age 0 on the post-natal 0-1 year chart. CONCLUSION: These new
      centiles, replacing those of the British 1990 reference, are more accurate than
      their predecessors which were biased due to the inclusion of post-natal data.

PMID- 21175305
TI  - Accountable care organizations--the fork in the road.

PMID- 21175306
TI  - Assessing an ACO prototype--Medicare's Physician Group Practice demonstration.

PMID- 21175307
TI  - Can Congress make you buy broccoli? And why that's a hard question.

PMID- 21175304
TI  - NFKBIA deletion in glioblastomas.
AB  - BACKGROUND: Amplification and activating mutations of the epidermal growth factor
      receptor (EGFR) oncogene are molecular hallmarks of glioblastomas. We
      hypothesized that deletion of NFKBIA (encoding nuclear factor of kappa-light
      polypeptide gene enhancer in B-cells inhibitor-alpha), an inhibitor of the EGFR
      signaling pathway, promotes tumorigenesis in glioblastomas that do not have
      alterations of EGFR. METHODS: We analyzed 790 human glioblastomas for deletions,
      mutations, or expression of NFKBIA and EGFR. We studied the tumor-suppressor
      activity of NFKBIA in tumor-cell culture. We compared the molecular results with
      the outcome of glioblastoma in 570 affected persons. RESULTS: NFKBIA is often
      deleted but not mutated in glioblastomas; most deletions occur in nonclassical
      subtypes of the disease. Deletion of NFKBIA and amplification of EGFR show a
      pattern of mutual exclusivity. Restoration of the expression of NFKBIA attenuated
      the malignant phenotype and increased the vulnerability to chemotherapy of cells
      cultured from tumors with NFKBIA deletion; it also reduced the viability of cells
      with EGFR amplification but not of cells with normal gene dosages of both NFKBIA
      and EGFR. Deletion and low expression of NFKBIA were associated with unfavorable
      outcomes. Patients who had tumors with NFKBIA deletion had outcomes that were
      similar to those in patients with tumors harboring EGFR amplification. These
      outcomes were poor as compared with the outcomes in patients with tumors that had
      normal gene dosages of NFKBIA and EGFR. A two-gene model that was based on
      expression of NFKBIA and O(6)-methylguanine DNA methyltransferase was strongly
      associated with the clinical course of the disease. CONCLUSIONS: Deletion of
      NFKBIA has an effect that is similar to the effect of EGFR amplification in the
      pathogenesis of glioblastoma and is associated with comparatively short survival.

PMID- 21175308
TI  - ACOs and the enforcement of fraud, abuse, and antitrust laws.

PMID- 21175309
TI  - Images in clinical medicine. Tinea.

PMID- 21175310
TI  - Courting danger while doing good--protecting global health workers from harm.

PMID- 21175314
TI  - Long-term mortality in childhood-onset epilepsy.
AB  - BACKGROUND: There are few studies on long-term mortality in prospectively
      followed, well-characterized cohorts of children with epilepsy. We report on long
      term mortality in a Finnish cohort of subjects with a diagnosis of epilepsy in
      childhood. METHODS: We assessed seizure outcomes and mortality in a population
      based cohort of 245 children with a diagnosis of epilepsy in 1964; this cohort
      was prospectively followed for 40 years. Rates of sudden, unexplained death were
      estimated. The very high autopsy rate in the cohort allowed for a specific
      diagnosis in almost all subjects. RESULTS: Sixty subjects died (24%); this rate
      is three times as high as the expected age- and sex-adjusted mortality in the
      general population. The subjects who died included 51 of 107 subjects (48%) who
      were not in 5-year terminal remission (i.e., >=5 years seizure-free at the time
      of death or last follow-up). A remote symptomatic cause of epilepsy (i.e., a
      major neurologic impairment or insult) was also associated with an increased risk
      of death as compared with an idiopathic or cryptogenic cause (37% vs. 12%,
      P<0.001). Of the 60 deaths, 33 (55%) were related to epilepsy, including sudden,
      unexplained death in 18 subjects (30%), definite or probable seizure in 9 (15%),
      and accidental drowning in 6 (10%). The deaths that were not related to epilepsy
      occurred primarily in subjects with remote symptomatic epilepsy. The cumulative
      risk of sudden, unexplained death was 7% at 40 years overall and 12% in an
      analysis that was limited to subjects who were not in long-term remission and not
      receiving medication. Among subjects with idiopathic or cryptogenic epilepsy,
      there were no sudden, unexplained deaths in subjects younger than 14 years of
      age. CONCLUSIONS: Childhood-onset epilepsy was associated with a substantial risk
      of epilepsy-related death, including sudden, unexplained death. The risk was
      especially high among children who were not in remission. (Funded by the Finnish
      Epilepsy Research Foundation.).

PMID- 21175312
TI  - Apixaban versus enoxaparin for thromboprophylaxis after hip replacement.
AB  - BACKGROUND: There are various regimens for thromboprophylaxis after hip
      replacement. Low-molecular-weight heparins such as enoxaparin predominantly
      inhibit factor Xa but also inhibit thrombin to some degree. Orally active,
      specific factor Xa inhibitors such as apixaban may provide effective
      thromboprophylaxis with a lower risk of bleeding and improved ease of use.
      METHODS: In this double-blind, double-dummy study, we randomly assigned 5407
      patients undergoing total hip replacement to receive apixaban at a dose of 2.5 mg
      orally twice daily or enoxaparin at a dose of 40 mg subcutaneously every 24
      hours. Apixaban therapy was initiated 12 to 24 hours after closure of the
      surgical wound; enoxaparin therapy was initiated 12 hours before surgery.
      Prophylaxis was continued for 35 days after surgery, followed by bilateral
      venographic studies. The primary efficacy outcome was the composite of
      asymptomatic or symptomatic deep-vein thrombosis, nonfatal pulmonary embolism, or
      death from any cause during the treatment period. Patients were followed for an
      additional 60 days after the last intended dose of study medication. RESULTS: A
      total of 1949 patients in the apixaban group (72.0%) and 1917 patients in the
      enoxaparin group (71.0%) could be evaluated for the primary efficacy analysis.
      The primary efficacy outcome occurred in 27 patients in the apixaban group (1.4%)
      and in 74 patients in the enoxaparin group (3.9%) (relative risk with apixaban,
      0.36; 95% confidence interval [CI], 0.22 to 0.54; P<0.001 for both noninferiority
      and superiority; absolute risk reduction, 2.5 percentage points; 95% CI, 1.5 to
      3.5). The composite outcome of major and clinically relevant nonmajor bleeding
      occurred in 129 of 2673 patients assigned to apixaban (4.8%) and 134 of 2659
      assigned to enoxaparin (5.0%) (absolute difference in risk, -0.2 percentage
      points; 95% CI, -1.4 to 1.0). CONCLUSIONS: Among patients undergoing hip
      replacement, thromboprophylaxis with apixaban, as compared with enoxaparin, was
      associated with lower rates of venous thromboembolism, without increased
      bleeding. (Funded by Bristol-Myers Squibb and Pfizer; ClinicalTrials.gov number,
      NCT00423319.).

PMID- 21175315
TI  - Variability in the measurement of hospital-wide mortality rates.
AB  - BACKGROUND: Several countries use hospital-wide mortality rates to evaluate the
      quality of hospital care, although the usefulness of this metric has been
      questioned. Massachusetts policymakers recently requested an assessment of
      methods to calculate this aggregate mortality metric for use as a measure of
      hospital quality. METHODS: The Massachusetts Division of Health Care Finance and
      Policy provided four vendors with identical information on 2,528,624 discharges
      from Massachusetts acute care hospitals from October 1, 2004, through September
      30, 2007. Vendors applied their risk-adjustment algorithms and provided predicted
      probabilities of in-hospital death for each discharge and for hospital-level
      observed and expected mortality rates. We compared the numbers and
      characteristics of discharges and hospitals included by each of the four methods.
      We also compared hospitals' standardized mortality ratios and classification of
      hospitals with mortality rates that were higher or lower than expected, according
      to each method. RESULTS: The proportions of discharges that were included by each
      method ranged from 28% to 95%, and the severity of patients' diagnoses varied
      widely. Because of their discharge-selection criteria, two methods calculated in
      hospital mortality rates (4.0% and 5.9%) that were twice the state average
      (2.1%). Pairwise associations (Pearson correlation coefficients) of discharge
      level predicted mortality probabilities ranged from 0.46 to 0.70. Hospital
      performance categorizations varied substantially and were sometimes completely
      discordant. In 2006, a total of 12 of 28 hospitals that had higher-than-expected
      hospital-wide mortality when classified by one method had lower-than-expected
      mortality when classified by one or more of the other methods. CONCLUSIONS: Four
      common methods for calculating hospital-wide mortality produced substantially
      different results. This may have resulted from a lack of standardized national
      eligibility and exclusion criteria, different statistical methods, or fundamental
      flaws in the hypothesized association between hospital-wide mortality and quality
      of care. (Funded by the Massachusetts Division of Health Care Finance and
      Policy.).

PMID- 21175316
TI  - Clinical practice. Glycemic control in the ICU.

PMID- 21175317
TI  - Images in clinical medicine. Metastatic pulmonary calcification.

PMID- 21175313
TI  - Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia.
AB  - BACKGROUND: Imatinib (400 mg daily) is considered the best initial therapy for
      patients with newly diagnosed chronic myeloid leukemia (CML) in the chronic
      phase. However, only a minority of patients treated with imatinib have a complete
      molecular remission. METHODS: We randomly assigned 636 patients with untreated
      chronic-phase CML to receive imatinib alone at a dose of 400 mg daily, imatinib
      (400 mg daily) plus cytarabine (20 mg per square meter of body-surface area per
      day on days 15 through 28 of each 28-day cycle) or pegylated interferon
      (peginterferon) alfa-2a (90 MUg weekly), or imatinib alone at a dose of 600 mg
      daily. Molecular and cytogenetic responses, time to treatment failure, overall
      and event-free survival, and adverse events were assessed. An analysis of
      molecular response at 12 months was planned. A superior molecular response was
      defined as a decrease in the ratio of transcripts of the tyrosine kinase gene BCR
      ABL to transcripts of ABL of 0.01% or less, corresponding to a reduction of 4
      log(10) units or more from the baseline level, as assessed by means of a real
      time quantitative polymerase-chain-reaction assay. RESULTS: At 12 months, the
      rates of cytogenetic response were similar among the four groups. The rate of a
      superior molecular response was significantly higher among patients receiving
      imatinib and peginterferon alfa-2a (30%) than among patients receiving 400 mg of
      imatinib alone (14%) (P=0.001). The rate was significantly higher among patients
      treated for more than 12 months than among those treated for 12 months or less.
      Gastrointestinal events were more frequent among patients receiving cytarabine,
      whereas rash and depression were more frequent among patients receiving
      peginterferon alfa-2a. CONCLUSIONS: As compared with other treatments, the
      addition of peginterferon alfa-2a to imatinib therapy resulted in significantly
      higher rates of molecular response in patients with chronic-phase CML. (Funded by
      the French Ministry of Health and others; ClinicalTrials.gov number,
      NCT00219739.).

PMID- 21175318
TI  - Case records of the Massachusetts General Hospital. Case 39-2010. A 19-year-old
      woman with nausea, jaundice, and pruritus.

PMID- 21175319
TI  - Therapeutic potential of oral factor Xa inhibitors.

PMID- 21175320
TI  - Neuromuscular blockers and ARDS.

PMID- 21175321
TI  - Neuromuscular blockers and ARDS.

PMID- 21175322
TI  - Neuromuscular blockers and ARDS.

PMID- 21175324
TI  - Intensive blood-pressure control in hypertensive chronic kidney disease.

PMID- 21175325
TI  - Intensive blood-pressure control in hypertensive chronic kidney disease.

PMID- 21175326
TI  - Intensive blood-pressure control in hypertensive chronic kidney disease.

PMID- 21175328
TI  - Gentamicin sponge for infection prophylaxis in colorectal surgery.

PMID- 21175330
TI  - Emergency treatment of asthma.

PMID- 21175331
TI  - Emergency treatment of asthma.

PMID- 21175333
TI  - Lessons from the mammography wars.

PMID- 21175334
TI  - Lessons from the mammography wars.

PMID- 21175335
TI  - Lessons from the mammography wars.

PMID- 21175337
TI  - Antimicrobial therapy for wound infections after catastrophic earthquakes.

PMID- 21175342
TI  - Noninvasive monitoring of therapy-induced microvascular changes in a pancreatic
      cancer model using dynamic contrast-enhanced magnetic resonance imaging with
      P846, a new low-diffusible gadolinium-based contrast agent.
AB  - A predictive technique in the management of patients with cancer could improve
      the therapeutic index by allowing better individualization of treatment. Dynamic
      contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive technique
      that can provide anatomical and physiological information on the tumor and its
      microenvironment. We studied the effect of chemotherapy (gemcitabine), anti
      angiogenesis therapy (sunitinib) and radiotherapy on the kinetics of DCE-MRI
      parameters in a preclinical model of pancreatic cancer using P846, a new low
      diffusible contrast agent. Mice underwent DCE-MRI before treatment (MRI1), after
      1 week of treatment (MRI2), and after 1 additional week (MRI3). Combined
      treatment with radiotherapy and sunitinib had a synergistic effect on tumor
      growth. In radiotherapy/sunitinib-treated mice, a decrease in K(trans) at MRI2
      predicted its superior antivascular and antitumor effect at an early time. An
      increased K(trans) at MRI2, as seen in gemcitabine- and gemcitabine/sunitinib
      treated mice, reflects increased permeability for P846 and might predict a
      smaller therapeutic effect at this early time. This study shows that the kinetics
      of DCE-MRI parameters depends on the contrast agent used. P846 appears to be a
      promising low-diffusible agent to monitor therapeutic effects in this preclinical
      cancer model, but further studies are needed to compare its behavior with Gd-DTPA
      and macromolecular-weight contrast agents. Sunitinib as a radiosensitizer is
      promising for future clinical trials in human pancreatic cancer.

PMID- 21175341
TI  - Quantitative and noninvasive assessment of prenatal X-ray-induced CNS
      abnormalities using magnetic resonance imaging.
AB  - Our purpose was to noninvasively assess formation of the microvasculature, blood
      brain barrier (BBB) and blood-CSF barrier formation of prenatal X-ray-induced CNS
      abnormalities using quantitative MRI. Eight pregnant female Sprague-Dawley rats
      were divided into two groups consisting of control and X-irradiated animals.
      After birth, 20 neonatal male rats were divided into four groups of five rats. To
      evaluate the development of the BBB, changes in T(1) induced by Gd-DTPA were
      compared quantitatively in normal and prenatally irradiated animals in the
      formative period 1 to 2 weeks after birth. To assess the abnormalities of the
      microvasculature, quantitative perfusion MRI and MR angiography were also used.
      Histology was also performed to evaluate the BBB (albumin) and vascular
      endothelial cells (laminin). Decreased cerebral blood flow (CBF) and
      angioarchitectonic abnormalities were observed in the prenatally irradiated rats.
      However, abnormalities of the BBB and blood-CSF barrier were not observed using
      Gd-enhanced MRI and albumin staining. Quantitative perfusion MRI, MR angiography
      and Gd-enhanced T(1) mapping are useful for assessing CNS disturbance after
      prenatal exposure to radiation. These techniques provide important diagnostic
      information for assessing the condition of patients during the early stages of
      life after accidental or unavoidable prenatal exposure to radiation.

PMID- 21175343
TI  - Effects of ionizing radiation on three-dimensional human vessel models:
      differential effects according to radiation quality and cellular development.
AB  - Little is known about the effects of space radiation on the human body. There are
      a number of potential chronic and acute effects, and one major target for
      noncarcinogenic effects is the human vasculature. Cellular stress, inflammatory
      response, and other radiation effects on endothelial cells may affect vascular
      function. This study was aimed at understanding the effects of space ionizing
      radiation on the formation and maintenance of capillary-like blood vessels. We
      used a 3D human vessel model created with human endothelial cells in a gel matrix
      to assess the effects of low-LET protons and high-LET iron ions. Iron ions were
      more damaging and caused significant reduction in the length of intact vessels in
      both developing and mature vessels at a dose of 80 cGy. Protons had no effect on
      mature vessels up to a dose of 3.2 Gy but did inhibit vessel formation at 80 cGy.
      Comparison with gamma radiation showed that photons had even less effect,
      although, as with protons, developing vessels were more sensitive. Apoptosis
      assays showed that inhibition of vessel development or deterioration of mature
      vessels was not due to cell death by apoptosis even in the case of iron ions.
      These are the first data to show the effects of radiation with varying linear
      energy transfer on a human vessel model.

PMID- 21175345
TI  - Age and hormonal status as determinants of cataractogenesis induced by ionizing
      radiation. I. Densely ionizing (high-LET) radiation.
AB  - Astronauts participating in extended lunar missions or the projected mission to
      Mars would likely be exposed to significant doses of high-linear energy transfer
      (LET) heavy energetic charged (HZE) particles. Exposure to even relatively low
      doses of such space radiation may result in a reduced latent period for and an
      increased incidence of lens opacification. However, the determinants of
      cataractogenesis induced by densely ionizing radiation have not been clearly
      elucidated. In the current study, we show that age at the time of exposure is a
      key determinant of cataractogenesis in rats whose eyes have been exposed to 2 Gy
      of (56)Fe ions. The rate of progression of cataractogenesis was significantly
      greater in the irradiated eyes of 1-year-old rats compared to young (56-day-old)
      rats. Furthermore, older ovariectomized rats that received exogenous estrogen
      treatment (17-beta-estradiol) commencing 1 week prior to irradiation and
      continuing throughout the period of observation of up to approximately 600 days
      after irradiation showed an increased incidence of cataracts and faster
      progression of opacification compared to intact rats with endogenous estrogen or
      ovariectomized rats. The same potentiating effect (higher incidence, reduced
      latent period) was observed for irradiated eyes of young rats. Modulation of
      estrogen status in the 1-year-old animals (e.g., removal of estrogen by
      ovariectomy or continuous exposure to estrogen) did not increase the latent
      period or reduce the incidence to that of intact 56-day-old rats. Since the rapid
      onset and progression of cataracts in 1-year-old compared to 56-day-old rats was
      independent of estrogen status, we conclude that estrogen cannot account for the
      age-dependent differences in cataractogenesis induced by high-LET radiation.

PMID- 21175346
TI  - UVB photoprotective role of mycosporines in yeast: photostability and antioxidant
      activity of mycosporine-glutaminol-glucoside.
AB  - Several yeast species are able to synthesize and accumulate UV-radiation
      absorbing mycosporine metabolites that are of unclear physiological function. In
      this work we analyzed the relationship between mycosporine-glutaminol glucoside
      (MGG) production, cell survival after UVB irradiation, and formation of
      cyclobutane pyrimidine dimers (CPDs). We also assessed the photostability and
      singlet oxygen quenching activity of MGG. A set of nine isolates of the
      basidiomycetous yeast Cryptococcus steppossus cultured in both dark and light
      conditions was used for the studies. Survival of the UVB-irradiated isolates and
      MGG concentration had a linear relationship when the concentration was over 2.5
      mg g(-1). CPD accumulation and MGG accumulation were inversely related. MGG in
      aqueous solution was photostable with a photodecomposition quantum yield of 1.16
      * 10(-5). MGG quenching of singlet oxygen was also observed, and the rate
      constant for the process in D(2)O was 5.9 * 10(7) M(-1) s(-1). Our results
      support the idea that MGG plays an important role as a UVB photoprotective
      metabolite in yeasts by protecting against direct damage on DNA and probably
      against indirect damage by singlet oxygen quenching.

PMID- 21175344
TI  - Captopril and losartan for mitigation of renal injury caused by single-dose total
      body irradiation.
AB  - It is known that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin
      II type-1 receptor blockers (ARBs) can be used to mitigate radiation-induced
      renal injury. However, for a variety of reasons, these previous results are not
      directly applicable to the development of agents for the mitigation of injuries
      caused by terrorism-related radiation exposure. As part of an effort to develop
      an animal model that would fit the requirements of the U.S. Food and Drug
      Administration (FDA) "Animal Efficacy Rule", we designed new studies which used
      an FDA-approved ACEI (captopril) or an FDA-approved ARB (losartan, Cozaar(r))
      started 10 days after a single total-body irradiation (TBI) at drug doses that
      are equivalent (on a g/m(2)/day basis) to the doses prescribed to humans.
      Captopril and losartan were equally effective as mitigators, with DMFs of 1.23
      and 1.21, respectively, for delaying renal failure. These studies show that
      radiation nephropathy in a realistic rodent model can be mitigated with relevant
      doses of FDA-approved agents. This lays the necessary groundwork for pivotal
      rodent studies under the FDA Animal Efficacy Rule and provides an outline of how
      the FDA-required large-animal studies could be designed.

PMID- 21175347
TI  - Photoactivated hypericin induces downregulation of HER2 gene expression.
AB  - Photodynamic therapy is an alternative method for cancer treatment in which a
      photosensitizer exposed to a light source of suitable wavelength is excited and
      can subsequently react through free radical mechanisms. Recently, oxygen free
      radical-mediated changes in gene expression have been established. The present
      study shows the effect of photoactivated hypericin on the expression of the human
      epidermal growth factor receptor 2 (HER2) oncogene at both the mRNA and the
      protein level in SKBR-3 and MCF-7 breast adenocarcinoma cell lines. The
      photodynamic therapy-induced decrease in mRNA expression was reversed by the
      singlet oxygen scavenger trolox, which supports a role for singlet oxygen. In
      addition, prevention of the generation of reactive oxygen species by pretreatment
      with trolox effectively blocked the antiproliferation activity of photoactivated
      hypericin. These results may have important implications at least for recurrent
      breast cancer with HER2 expression alone or in combination with conventional
      therapies.

PMID- 21175348
TI  - SOD2-mediated effects induced by WR1065 and low-dose ionizing radiation on
      micronucleus formation in RKO human colon carcinoma cells.
AB  - RKO36 cells exposed to either WR1065 or 10 cGy X rays show elevated SOD2 gene
      expression and SOD2 enzymatic activity. Cells challenged at this time with 2 Gy
      exhibit enhanced radiation resistance. This phenomenon has been identified as a
      delayed radioprotective effect or an adaptive response when induced by thiols or
      low-dose radiation, respectively. In this study we investigated the relative
      effectiveness of both WR1065 and low-dose radiation in reducing the incidence of
      radiation-induced micronucleus formation in binucleated RKO36 human colon
      carcinoma cells. The role of SOD2 in this process was assessed by measuring
      changes in enzymatic activity as a function of the inducing agent used, the level
      of protection afforded, and the inhibitory effects of short interfering RNA (SOD2
      siRNA). Both WR1065 and 10 cGy X rays effectively induced a greater than
      threefold elevation in SOD2 activity 24 h after exposure. Cells irradiated at
      this time with 2 Gy exhibited a significant resistance to micronucleus formation
      (P < 0.05; Student's two-tailed t test). This protective effect was significantly
      inhibited in cells transfected with SOD2 siRNA. SOD2 played an important role in
      the adaptive/delayed radioprotective response by inhibiting the initiation of a
      superoxide anion-induced ROS cascade leading to enhanced mitochondrial and
      nuclear damages.

PMID- 21175349
TI  - Transcriptome characterization uncovers the molecular response of hematopoietic
      cells to ionizing radiation.
AB  - Ionizing radiation causes rapid and acute suppression of hematopoietic cells that
      manifests as the hematopoietic syndrome. However, the roles of molecules and
      regulatory pathways induced in vivo by irradiation of different hematopoietic
      cells have not been completely elaborated. Using a strategy that combined
      different microarray bioinformatics tools, we identified gene networks that might
      be involved in the early response of hematopoietic cells radiation response in
      vivo. The grouping of similar time-ordered gene expression profiles using quality
      threshold clustering enabled the successful identification of common binding
      sites for 56 transcription factors that may be involved in the regulation of the
      early radiation response. We also identified novel genes that are responsive to
      the transformation-related protein 53; all of these genes were biologically
      validated in p53-transgenic null mice. Extension of the analysis to purified bone
      marrow cells including highly purified long-term hematopoietic stem cells,
      combined with functional classification, provided evidence of gene expression
      modifications that were largely unknown in this primitive population. Our
      methodology proved particularly useful for analyzing the transcriptional
      regulation of the complex ionizing radiation response of hematopoietic cells. Our
      data may help to elucidate the molecular mechanisms involved in tissue
      radiosensitivity and to identify potential targets for improving treatment in
      radiation emergencies.

PMID- 21175350
TI  - Differential role of DNA-PKcs phosphorylations and kinase activity in
      radiosensitivity and chromosomal instability.
AB  - The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is the key
      functional element in the DNA-PK complex that drives nonhomologous end joining
      (NHEJ), the predominant DNA double-strand break (DSB) repair mechanism operating
      to rejoin such breaks in mammalian cells after exposure to ionizing radiation. It
      has been reported that DNA-PKcs phosphorylation and kinase activity are critical
      determinants of radiosensitivity, based on responses reported after irradiation
      of asynchronously dividing populations of various mutant cell lines. In the
      present study, the relative radiosensitivity to cell killing as well as
      chromosomal instability of 13 DNA-PKcs site-directed mutant cell lines (defective
      at phosphorylation sites or kinase activity) were examined after exposure of
      synchronized G(1) cells to (137)Cs gamma rays. DNA-PKcs mutant cells defective in
      phosphorylation at multiple sites within the T2609 cluster or within the PI3K
      domain displayed extreme radiosensitivity. Cells defective at the S2056 cluster
      or T2609 single site alone were only mildly radiosensitive, but cells defective
      at even one site in both the S2056 and T2609 clusters were maximally
      radiosensitive. Thus a synergism between the capacity for phosphorylation at the
      S2056 and T2609 clusters was found to be critical for induction of
      radiosensitivity.

PMID- 21175351
TI  - Persistence of DNA double-strand breaks in normal human cells induced by
      radiation-induced bystander effect.
AB  - Our previous study suggested that the DNA double-strand breaks (DSBs) induced by
      very low X-ray doses are largely due to bystander effects. The aim of this study
      was to verify whether DSBs created by radiation-induced bystander effects are
      likely to be repaired. We examined the generation of DSBs in cells by enumeration
      of phosphorylated ataxia telangiectasia mutated (ATM) foci, which are correlated
      with DSB repair, in normal human fibroblast cells (MRC-5) after X irradiation at
      doses ranging from 1 to 1000 mGy. At 24 h after irradiation, 100% (1.2 mGy), 58%
      (20 mGy), 12% (200 mGy) and 8.5% (1000 mGy) of the initial number of
      phosphorylated ATM foci were detected. The number of phosphorylated ATM foci in
      MRC-5 cells treated with lindane, an inhibitor of radiation-induced bystander
      effects, prior to X irradiation was assessed; phosphorylated ATM foci were not
      observed at 5 h (20 mGy) or 24 h (200 mGy) postirradiation. We also counted the
      number of phosphorylated ATM foci in MRC-5 cells cocultured with MRC-5 cells
      irradiated with 20 mGy. After 48 h of coculture, 81% of the initial numbers of
      phosphorylated ATM foci remained. These findings suggest that DSBs induced by the
      radiation-induced bystander effect persist for long periods, whereas DSBs induced
      by direct radiation effects are repaired relatively quickly.

PMID- 21175353
TI  - Simulation of electron-beam irradiation of skin tissue model.
AB  - Monte Carlo simulation of electrons stopping in liquid water was used to model
      the penetration and quality of electron-beam irradiation incident on the full
      thickness EpiDermTM skin model (EpiDermFTTM MatTek, Ashland, VA). This 3D tissue
      model has a fully developed basement membrane separating an epidermal layer of
      keratinocytes in various stages of differentiation from a dermal layer of
      fibroblasts embedded in collagen. The simulations were motivated by a desire to
      selectively expose the epidermal layer to low-linear energy transfer (LET)
      radiation in the presence of a nonirradiated dermal layer. The variable-energy
      electron microbeam at the Pacific Northwest National Laboratory (PNNL) was used
      as a model of device characteristics and irradiation geometry. At the highest
      beam energy available (90 keV), we estimate that no more than a few percent of
      the beam energy will be deposited in the dermal layer. Energy deposition spectra
      were calculated for 10-um-thick layers near the 10th, 50th and 90th percentiles
      of penetration by the 90 keV electron beam. Bimodal spectra showed an increasing
      component of "stoppers" with increasing depth, which increases the probability of
      large energy deposition events. Nevertheless, screening by tissue above the layer
      of interest is the main factor determining energy deposited at a given depth.

PMID- 21175352
TI  - Base damage immediately upstream from double-strand break ends is a more severe
      impediment to nonhomologous end joining than blocked 3'-termini.
AB  - Radiation-induced DNA double-strand breaks (DSBs) are critical cytotoxic lesions
      that are typically repaired by nonhomologous end joining (NHEJ) in human cells.
      Our previous work indicated that the highly cytotoxic DSBs formed by (125)I decay
      possess base damage clustered within 8 to 10 bases of the break and 3'-phosphate
      (P) and 3'-OH ends. This study examined the effect of such structures on NHEJ in
      in vitro assays employing either (125)I decay-induced DSB linearized plasmid DNA
      or structurally defined duplex oligonucleotides. Duplex oligonucleotides that
      possess either a 3'-P or 3'-phosphoglycolate (PG) or a ligatable 3'-OH end with
      either an AP site or an 8-oxo-dG 1 nucleotide upstream (-1n) from the 3'-terminus
      have been examined for reparability. Moderate to severe end-joining inhibition
      was observed for modified DSB ends or 8-oxo-dG upstream from a 3'-OH end. In
      contrast, abolition of end joining was observed with duplexes possessing an AP
      site upstream from a ligatable 3'-OH end or for a lesion combination involving 3'
      P plus an upstream 8-oxo-dG. In addition, base mismatches at the -1n position
      were also strong inhibitors of NHEJ in this system, suggesting that
      destabilization of the DSB terminus as a result of base loss or improper base
      pairing may play a role in the inhibitory effects of these structures.
      Furthermore, we provide data indicating that DSB end joining is likely to occur
      prior to removal or repair of base lesions proximal to the DSB terminus. Our
      results show that base damage or base loss near a DSB end may be a severe block
      to NHEJ and that complex combinations of lesions presented in the context of a
      DSB may be more inhibitory than the individual lesions alone. In contrast,
      blocked DSB 3'-ends alone are only modestly inhibitory to NHEJ. Finally, DNA
      ligase activity is implicated as being responsible for these effects.

PMID- 21175354
TI  - Lung cancer from radon: a two-stage model analysis of the WISMUT Cohort, 1955
      1998.
AB  - A biologically based two-stage carcinogenesis model is applied to epidemiological
      data for lung cancer mortality in a large uranium miner cohort of the WISMUT
      company (Germany). To date, this is the largest uranium miner cohort analyzed by
      a mechanistic model, comprising 35,084 workers among whom 461 died from lung
      cancer in the follow-up period 1955-1998. It comprises only workers who were
      first employed between 1955 and 1989 and contains information on annual exposures
      to radon progeny. We fitted the model's free parameters, including the average
      growth time of one malignant cell into a lethal tumor. This lag time has an
      extraordinary value of 13 to 14 years, larger than that previously used or found
      in miner studies. Even though cohort-wide information on smoking habits is
      limited and the calendar-year dependence of tobacco smoke exposure was only
      implicitly accounted for by a birth cohort effect, we find good agreement between
      the modeled (expected) and empirical (observed) lung cancer mortality. Model
      calculations of excess relative lung cancer death risk agree well with those from
      the descriptive, BEIR VI-type exposure-age-concentration model for WISMUT miners.
      The large variety of exposure profiles in the cohort leads to a well-determined
      mechanistic model that in principle allows for an extrapolation from occupational
      to indoor radon exposure.

PMID- 21175355
TI  - Radiation exposures in medicine: biological and public health significance.

PMID- 21175356
TI  - Redox pioneer: Professor Wulf Droge.
AB  - Dr. Wulf Droge is recognized here as a redox pioneer because he has published as
      first author an article on antioxidant/redox biology that has been cited more
      than 2000 times and over 10 articles that have been cited more than 100 times.
      One of the key discoveries (1987) was the stimulatory effect of superoxide
      radicals and hydrogen peroxide on lymphocyte functions, which triggered a series
      of studies on the role of reactive oxygen species, glutathione, and its precursor
      cysteine in physiological and pathological processes. He discovered abnormally
      low cysteine and glutathione levels in human immunodeficiency virus-infected
      patients and the age-related decline in the postabsorptive plasma cysteine
      concentration, which is believed to cause age-related oxidative stress. He
      developed a theoretical concept of the mechanism of aging and death, which is
      outlined in his books Avoiding the First Cause of Death and Challenging the
      Limits of the Human Lifespan.

PMID- 21175358
TI  - Microfluidic LC-MS for analysis of small-volume biofluid samples: where we have
      been and where we need to go.

PMID- 21175359
TI  - New findings in liquid chromatography in the pharmaceutical domain.

PMID- 21175357
TI  - Efficacy of Tat-conjugated ritonavir-loaded nanoparticles in reducing HIV-1
      replication in monocyte-derived macrophages and cytocompatibility with
      macrophages and human neurons.
AB  - Human immunodeficiency virus (HIV)-1 targets mononuclear phagocytes (MP), which
      disseminate infection to organs such as brain, spleen and lymph. Thus MP, which
      include microglia, tissue macrophages and infiltrating monocyte-derived
      macrophages (MDM), are important target of anti-HIV-1 drug therapy. Most of the
      currently used antiretroviral drugs are effective in reducing viral loadin the
      periphery but cannot effectively eradicate infection from tissue reservoirs such
      as brain MP. HIV-1 infection of the central nervous system can lead to a wide
      variety of HIV-1-associated neurocognitive disorders. In this study, we
      demonstrate that ritonavir-loaded nanoparticles (RNPs) are effective in
      inhibiting HIV-1 infection of MDM. Reduced infection is observed in multiple read
      out systems including reduction of cytopathic effects, HIV-1 p24 protein
      secretion and production of progeny virions. Furthermore, the RNPs retained
      antiretroviral efficacy after being removed from MDM cultures. As HIV-1-infected
      cells in the brain are likely to survive for a long period of time, both acute
      and chronic infection paradigms were evaluated. Tat-peptide-conjugated RNPs (Tat
      RNP) were effective in both short-term and long-term HIV-1-infected MDM.
      Importantly, we confirm that delivery of RNPs, both with and without Tat-peptide
      conjugation, is toxic neither to MDM nor to neural cells, which may be bystander
      targets of the nanoformulations. In conclusion, Tat-NPs could be a safe and
      effective way of delivering anti-HIV-1 drugs for controlling viral replication
      occurring within brain MP.

PMID- 21175361
TI  - Conference report: summary of the 2010 Applied Pharmaceutical Analysis
      Conference.
AB  - This year, the Applied Pharmaceutical Analysis meeting changed its venue to the
      Grand Tremont Hotel in Baltimore, MD, USA. Proximity to Washington presented the
      opportunity to have four speakers from the US FDA. The purpose of the 4-day
      conference is to provide a forum in which pharmaceutical and CRO scientists can
      discuss and develop best practices for scientific challenges in bioanalysis and
      drug metabolism. This year's theme was 'Bioanalytical and Biotransformation
      Challenges in Meeting Global Regulatory Expectations & New Technologies for Drug
      Discovery Challenges'. Applied Pharmaceutical Analysis continued its tradition of
      highlighting new technologies and its impact on drug discovery, drug metabolism
      and small molecule-regulated bioanalysis. This year, the meeting included an
      integrated focus on metabolism in drug discovery and development. Middle and
      large molecule (biotherapeutics) drug development, immunoassay, immunogenicity
      and biomarkers were also integrated into the forum. Applied Pharmaceutical
      Analysis offered an enhanced diversity of topics this year while continuing to
      share experiences of discovering and developing new medicines.

PMID- 21175362
TI  - Conference report: Seventh Exploratory Measurement Science Group Symposium.
AB  - The impressive 18th Century Ardgour House again played host to the seventh annual
      Exploratory Measurement Science Group Symposium. The Symposium was organised as a
      study retreat for young and established scientists who share a common interest in
      the development and application of advanced analytical instrumentation. Speakers
      from a wide range of backgrounds in academia, industry and government were
      invited to present and discuss their research interests surrounded by the
      stunning Highland scenery of Fort William.

PMID- 21175363
TI  - Young investigator. Barry Zee.

PMID- 21175364
TI  - Determination of free and deconjugated testosterone and epitestosterone in urine
      using SPME and LC-MS/MS.
AB  - BACKGROUND: A thin sheet of polydimethylsilosane membrane was used as an
      extraction phase for solid-phase microextraction. Compared with fiber or rod
      solid-phase microextraction geometries, the thin film exhibited much higher
      extraction capacity without sacrificing extraction time due to its higher area-to
      volume ratio. The analytical method involved direct extraction of unconjugated
      testosterone (T) and epitestosterone (ET) followed by separation on a C18 column
      and detection by selected reaction monitoring in positive ionization mode.
      RESULTS: The limit of detection was 1 ng/l for both T and ET. After method
      validation, free (unconjugated) T and ET were extracted and quantified in real
      samples. Since T and ET are extensively metabolized, the proposed method was also
      applied to extract the steroids after enzymatic deconjugation of urinary-excreted
      steroid glucuronides. CONCLUSION: The proposed method allows quantification of
      both conjugated and unconjugated steroids, and revealed that there was a change
      in the ratio of T to ET after enzymatic deconjugation, indicating different rates
      of metabolism.

PMID- 21175365
TI  - Bioequivalence of venlafaxine modified-release capsule revisited with an
      innovative approach using experimental and predictive models.
AB  - BACKGROUND: To evaluate the venlafaxine:O-desmethyl venlafaxine (active
      metabolite) in vivo formation ratio (MR) in three independent bioequivalence (BE)
      studies consisting of single-dosed (under fasted and fed conditions) and multiple
      dosed clinical trials on healthy subjects. The pooled data pharmacokinetic (PK)
      analysis demonstrates a model to conduct enantiomer/racemate/active metabolite
      bioanalysis for regulatory submission of bioavailability/bioequivalence (BA/BE)
      studies using an interesting MR concept. RESULTS: BE was established for all
      three studies. Moreover, the venlafaxine:O-desmethyl venlafaxine MR for C(max)
      and AUC(last) differed by more than 50% for fasted and fed single-dosed studies,
      while pooled data analysis found the MR for C(max) to be approximately 0.63 and
      the AUC to be approximately 0.36 for both test and reference drugs. However,
      negligible variation was observed for both rate and extent of drug and active
      metabolite absorption into the systemic circulation at steady state, as the MR
      for both C(max) and AUC was approximately 0.62. CONCLUSIONS: The
      applications/consequences of the above results are immense. First, an achiral
      assay for venlafaxine and O-desmethyl venlafaxine estimation in human plasma has
      been justified for the regulatory acceptance of BA/BE studies, supported with
      both single- and multiple-dosed PK data showing negligible variation in terms of
      MR at C(max). Second, the current investigation shows the MR to be within +/-10%
      when compared with the single-dosed reported study on a western population.
      Third, the racial effect would not lead to any significant clinical outcome using
      an interchangeable venlafaxine 150-mg capsule manufactured by Ranbaxy with an
      Efexor 150-mg capsule manufactured by Wyeth. Furthermore, a decision tree is
      proposed to evaluate if a racemate or an enantiomer drug and active metabolite
      bioanalysis should be executed for BA/BE regulatory submission using respective
      achiral or chiral assays when the drug moiety is a racemate or an enantiomer,
      formulated in modified-release dosage forms.

PMID- 21175366
TI  - A screening UHPLC-MS/MS method for the analysis of amyloid peptides in
      cerebrospinal fluid of preclinical species.
AB  - BACKGROUND: Amyloid peptides are established biomarkers for Alzheimer's disease
      but their analysis presents major challenges. RESULTS: In this article, we
      describe the use of ultra high-performance LC and API4000 triple quadrupole
      instrumentation for the quantification of amyloid peptides (Abeta(1-38) and
      Abeta(1-42)) in cerebrospinal fluid (CSF), using electrospray ionization with
      negative ion multiple reaction monitoring transitions. Sample preparation was
      simplified by the addition of acetonitrile and ammonium hydroxide. Although
      excellent sensitivity and precision was demonstrated, we observed differences in
      matrix suppression effects when using artificial CSF versus canine CSF for
      calibration curves and quality control samples. CONCLUSION: A case study shows
      that the method can be used to determine the relative levels of two key peptides
      (Abeta(1-38) and Abeta(1-42)) compared with their predose values (a screening
      assay) in support of preclinical studies.

PMID- 21175367
TI  - Capsule review on bioanalytical method transfer: opportunities and challenges for
      chromatographic methods.
AB  - With the globalization of drug development activities, transferring a validated
      bioanalytical procedure to a different site within a pharmaceutical company, or
      to one or multiple contract research organizations has been dramatically
      increased in recent years. Undeniably, bioanalytical method transfer is the
      needed step prior to routine sample analysis at the receiving laboratory. It is
      clearly stated in the 2001 US FDA Guidance on Bioanalytical Method Validation
      that a partial validation is needed for method transfer between laboratories. In
      the current EMA draft guidelines on method validation, the necessity of a method
      transfer is also emphasized. However, the above guidelines do not give many
      details on how and when a method transfer validation should be conducted. There
      is a need for a step-by-step deliberation on the overall strategies, procedures
      and even technical details for a successful bioanalytical method transfer. In
      this article, we review the contemporary information available in the scientific
      literature on method transfer and illustrate various bioanalytical method
      transfer scenarios using case studies. A 'flexible and fit-for-purpose'
      bioanalytical method transfer strategy is proposed.

PMID- 21175368
TI  - Hair: a complementary source of bioanalytical information in forensic toxicology.
AB  - Hair has been used for years in the assessment and documentation of human
      exposure to drugs, as it presents characteristics that make it extremely valuable
      for this purpose, namely the fact that sample collection is performed in a
      noninvasive manner, under close supervision, the possibility of collecting a
      specimen reflecting a similar timeline in the case of claims or suspicion of a
      leak in the chain of custody, and the increased window of detection for the
      drugs. For these reasons, testing for drugs in hair provides unique and useful
      information in several fields of toxicology, from which the most prominent is the
      possibility of studying individual drug use histories by means of segmental
      analysis. This paper will review the unique role of hair as a complementary
      sample in documenting human exposure to drugs in the fields of clinical and
      forensic toxicology and workplace drug testing.

PMID- 21175369
TI  - Quality control and analytical techniques for biopharmaceuticals.
AB  - Biopharmaceuticals are complex products and to ensure their batch-to-batch
      consistency and continuing quality the use of a combination of complementary
      analytical tests is required. Regulatory guidelines indicate quality attributes
      of different product classes to be included in the specifications for product
      release. Whilst the continuing development of sophisticated physicochemical
      techniques make them increasingly powerful for defining product identity,
      integrity, purity and the consistency of the manufacturing process, the results
      generated are not easily related to the biological activity. Consequently, a
      bioassay is normally required in the quality control to determine the potency,
      that is, the quantitative measure of the product's ability to cause a specific
      biological effect in a defined biological system. A wide, and rapidly increasing,
      range of bioassay systems exist, each type with particular advantages and
      disadvantages.

PMID- 21175370
TI  - Bio-sample preparation and analytical methods for the determination of tricyclic
      antidepressants.
AB  - An extended and comprehensive review is presented herein, focusing on sample
      preparation (pretreatment and extraction) and different analytical methods
      applied for the quantification of tricyclic antidepressants. These procedures are
      relevant tools in clinical and forensic toxicology. It is revealed that SPE, for
      sample preparation, and HPLC, using reversed-phase alkyl (C18) or cyanopropyl
      bonded silica columns for the analytes separation, are effective and versatile
      methods for assay of tricyclic antidepressants. These methods enable achievable
      detection limits using UV/diode array detection, readily available in most
      laboratories, down to 1-8 ng ml(-1), and using electron capture detection better
      than 1 ng ml(-1), which is lower than that for nitrogen-phosphorus detector. MS
      interfaced with electrospray ionization offered similar sensitivity, whilst sonic
      spray ionization provided detection down to 0.03 ng ml(-1). A brief discussion on
      chemical structures, metabolism and mechanism of action of this group of drugs is
      also presented.

PMID- 21175373
TI  - Tolerability of solifenacin and oxybutynin immediate release in older (> 65
      years) and younger (<= 65 years) patients with overactive bladder: sub-analysis
      from a Canadian, randomized, double-blind study.
AB  - OBJECTIVE: Overactive bladder (OAB) is a common condition whose prevalence
      increases with age. Antimuscarinic agents are the pharmacologic treatment of
      choice, but adverse events such as dry mouth may lead to early discontinuation.
      The purpose of this analysis was to compare the incidence and severity of dry
      mouth and other adverse events with solifenacin 5 mg/day and oxybutynin immediate
      release (IR) 15 mg/day in patients <= 65 years and >65 years in the Canadian
      VECTOR study (VEsicare in Comparison To Oxybutynin for oveRactive bladder
      patients). RESEARCH DESIGN AND METHODS: VECTOR was a randomized, multicentre,
      prospective, double-blind, double-dummy study in 132 subjects with >= 1 urgency
      episode per 24 h, with or without urgency incontinence, and >= 8 micturitions per
      24 h for >= 3 months. After a 2-week washout, patients received solifenacin 5 mg
      once daily or oxybutynin IR 5 mg tid for 8 weeks. For the current post-hoc
      analysis, adverse events were evaluated in subgroups of patients <= 65 years and
      >65 years, using a full logistic regression model, multinomial logit regression
      model and reduced model. CLINICAL TRIAL REGISTRATION: NCT00431041. RESULTS: The
      incidence and severity of dry mouth and other adverse events with solifenacin
      were similar between younger and older patients. In both age subgroups,
      solifenacin 5 mg/day was associated with fewer episodes and lower severity of dry
      mouth, and a lower discontinuation rate, compared with oxybutynin IR 15 mg/day.
      CONCLUSIONS: Solifenacin 5 mg/day was better tolerated than oxybutynin IR 15
      mg/day in younger (<= 65 years) and older (> 65 years) subgroups. Solifenacin was
      equally well tolerated in both age subgroups. Limitations of the analysis were
      that the study was not preplanned to perform post-hoc subgroup analysis, patients
      knew that dry mouth was a primary outcome, and the study used fixed doses of each
      drug.

PMID- 21175374
TI  - Home pregnancy test compared to standard-of-care ultrasound dating in the
      assessment of pregnancy duration.
AB  - OBJECTIVE: To determine the level of agreement between the Clearblue Digital
      Pregnancy Test with Conception Indicator home pregnancy test and standard-of-care
      ultrasound in assessing pregnancy duration in a real-life, observational setting
      encompassing routine, clinical care. RESEARCH DESIGN AND METHODS: This was a
      prospective observational study of non-pregnant women seeking conception. Women
      collected daily urine samples from day 1 of their next menstrual cycle. If any
      volunteer became pregnant, daily urine samples continued to be collected for 43
      days after the LH surge. Samples from day -7 to day +28 relative to the expected
      period (LH surge + 15 days) were tested using the home pregnancy test. This
      categorised any resulting pregnancies into one of three groups: 1-2 weeks, 2-3
      weeks, and 3+ weeks since conception. Information from the standard UK ultrasound
      dating scan was also recorded by the midwife, including the expected delivery
      date according to ultrasound and the expected delivery date according to LMP.
      MAIN OUTCOME MEASURES: Full data were available from 52 pregnant women who had
      conceived naturally. During the study analysis, 4786 urine samples were cross
      compared with 52 routine 12-week NHS ultrasound assessments and the level of
      agreement between home pregnancy testing and standard-of-care ultrasound in
      determining pregnancy duration was calculated. RESULTS: The agreement between the
      gestational age as calculated by the home pregnancy test result and the exact
      midwife-recorded gestational age using ultrasound was 82.3%. However, when a +/-
      5-day range was applied to the ultrasound reading (as per routine UK clinical
      practice), the level of agreement was 98%. CONCLUSIONS: The home pregnancy test
      provides a significantly high (98%) level of agreement with standard-of-care
      ultrasound when assessing pregnancy duration in a real-life, observational
      setting which closely mirrors daily clinical practice.

PMID- 21175372
TI  - A new isolation method of human limbal progenitor cells by maintaining close
      association with their niche cells.
AB  - In human corneal epithelium, self-renewal and fate decision of stem cells are
      highly regulated in a niche microenvironment called palisades of Vogt in the
      limbus. Herein, we discovered that digestion with dispase, which cleaves off the
      basement membrane, did not remove the entire basal epithelial progenitor cells.
      In contrast, digestion with collagenase isolated on cluster consisting of not
      only entire epithelial progenitor cells but also their closely associated
      mesenchymal cells because of better preservation of some basement membrane
      matrix. Collagenase isolated more basal epithelial progenitor cells, which were
      p63alpha+ and small in the size (8 MUm in diameter), and generated significantly
      more holoclones and meroclones on 3T3 fibroblast feeder layers than dispase.
      Further, collagenase isolated more small pan-cytokeratin-/p63alpha-/vimentin+
      cells with the size as small as 5 MUm in diameter and heterogeneously expressing
      vimentin, Oct4, Sox2, Nanog, Rex1, Nestin, N-cadherin, SSEA4, and CD34.
      Maintenance of close association between them led to clonal growth in a serum
      free, low-calcium medium, whereas disruption of such association by trypsin/EDTA
      resulted in no clonal growth unless cocultured with 3T3 fibroblast feeder layers.
      Similarly, on epithelially denuded amniotic membrane, maintenance of such
      association led to consistent and robust epithelial outgrowth, which was also
      abolished by trypsin/EDTA. Epithelial outgrowth generated by collagenase-isolated
      clusters was significantly larger in diameter and its single cells yielded more
      holoclones on 3T3 fibroblast feeder layers than that from dispase-isolated
      sheets. This new isolation method can be used for exploring how limbal epithelial
      stem cells are regulated by their native niche cells.

PMID- 21175375
TI  - Modelled cost-effectiveness of high cut-off haemodialysis compared to standard
      haemodialysis in the management of myeloma kidney.
AB  - BACKGROUND: Approximately 10-20% of multiple myeloma patients experience dialysis
      dependent renal failure. This is principally due to myeloma kidney, a
      tubulointerstitial injury caused by high circulating concentrations of monoclonal
      free light chains. Studies have found that between 3% and 37% of patients with
      myeloma kidney requiring dialysis recover renal function. In-vivo studies
      indicate that extended haemodialysis using high cut-off dialysers (HCO-HD) can
      remove significant quantities of free light chains and is associated with a renal
      recovery rate of 63-74% in these patients. OBJECTIVE: The objective of this study
      was to assess the cost-effectiveness of HCO-HD compared to standard HD in the
      management of myeloma kidney. METHODS: The study used a lifetime Excel-based
      decision tree model that followed all patients from treatment of the initial
      presentation with myeloma kidney requiring dialysis to death. It was populated
      with published clinical data, United Kingdom costs and expert opinion, using a
      National Health Service perspective and 3.5% annual discounting. RESULTS: HCO-HD
      was dominant to standard HD, meaning it was both more effective (greater life
      years and quality adjusted life years) and less costly, due to a greater increase
      in the proportion of patients recovering renal function. The model projected
      lifetime costs of L31,345 per patient for patients treated with standard
      haemodialysis only and L24,845 for the new treatment (discounted). The model
      predicted an average survival of 19.92 months for patients on standard HD and
      33.90 months for the new therapy (discounted). CONCLUSIONS: The analysis found
      that treatment of myeloma kidney using an extended schedule of HCO-HD may
      substantially improve renal recovery in multiple myeloma patients compared to
      standard HD, resulting in greater life expectancy and cost savings due to avoided
      chronic dialysis. Limitations of the study include those common to rare diseases
      including small study sizes and limited natural history data.

PMID- 21175376
TI  - Cost effectiveness of posaconazole in the prophylaxis of invasive fungal
      infections in acute leukaemia patients for the French healthcare system.
AB  - BACKGROUND: Acute myeloblastic leukaemia (AML) patients are at high risk of
      suffering from invasive fungal infections (IFI). Posaconazole demonstrated higher
      efficacy than standard azole agents (SAA) in the prophylaxis of IFI in this
      population. The authors estimated the cost effectiveness of posaconazole versus
      SAA in France. METHODS: A decision-tree model was developed to compare
      posaconazole with SAA with the results of a published clinical trial. Clinical
      events were modelled with chance nodes reflecting probabilities of IFI, IFI
      related death, and death from other causes. Medical resource consumption and
      costs were obtained from results of the clinical trial and from a dedicated
      survey on the costs of treating IFI using a retrospective chart review design.
      RESULTS: IFI treatment costs were estimated using medical files from 50 AML
      patients from six French centres, with a proven and probable IFI, who had been
      followed-up for 298 days on average. Direct costs directly related to IFI were
      estimated at ?51,033, including extra costs of index hospitalisation, costs of
      antifungal therapy and additional hospitalisations related to IFI treatment. The
      model indicated that the healthcare costs for the posaconazole strategy were
      ?5,223 (?2,697 for prophylaxis and ?2,526 for IFI management), which was ?859
      less than the ?6,083 in costs with SAA (?469 for prophylaxis and ?5614 for IFI
      management). A sensitivity analysis indicated that there was an 80% probability
      that prophylaxis using the posaconazole strategy would be superior. CONCLUSION:
      The findings from this analysis suggest that posaconazole use is a clinically and
      economically dominant strategy in the prophylaxis of IFI in AML patients, given
      the usual limits of economic models and the uncertainty of costs estimates.

PMID- 21175377
TI  - Inflammatory and structural biomarkers in acute traumatic spinal cord injury.
AB  - The paralysis of an acute spinal cord injury (SCI) remains a catastrophic
      condition for which there are currently no effective treatments. While the
      diagnosis of acute traumatic SCI is typically quite easy to make, distinguishing
      the exact degree of severity and prognosticating the extent of neurologic
      recovery are challenging. Functional neurologic measures are currently used to
      stratify injury severity and predict neurologic outcome. However, these measures
      are often impossible to determine in acutely injured patients. Additionally, for
      patients deemed to be of a specific injury severity, the variability in
      spontaneous neurologic recovery is high. Both of these issues severely impair the
      ability to perform clinical trials in novel therapies for SCI. Biomarkers that
      could more precisely define the severity of injury and better predict neurologic
      outcome would be extremely valuable. Furthermore, biological surrogate outcomes
      measures would be very useful in small preliminary clinical trials of novel
      therapies if they could inform decisions around the therapeutic regimen for
      subsequent larger clinical trials. This review highlights our ongoing work in
      establishing biomarkers for SCI using cerebrospinal fluid samples from acutely
      injured patients.

PMID- 21175378
TI  - Serum cholesterol measured by isotope dilution liquid chromatography tandem mass
      spectrometry.
AB  - BACKGROUND: Accurate cholesterol measurements are essential for the prevention
      and management of cardiovascular diseases. Quality assurance of cholesterol
      measurements requires reference methods. METHODS: An isotope dilution liquid
      chromatography mass spectrometric (ID/LC/MS) method was developed. Serum samples
      were sampled volumetrically using automated dilutors, treated with potassium
      hydroxide and equilibrated with 3,4-(13)C(2) cholesterol. The natural cholesterol
      and the internal standard were extracted with hexane and oxidized to cholest-4-en
      3,6-diones with chromic acid. The oxidation products were separated on reversed
      phase LC and detected by tandem MS. The method was calibrated using aqueous
      cholesterol calibrators and the calibration function was established with a
      polynomial regression. RESULTS: The correlation coefficients of the calibration
      curves were always >0.9999. The coefficients of variation (CV) of the volumetric
      sampling and the LC/MS analysis averaged 0.22% and 0.50%, respectively, and the
      total measurement CV was 0.60%. Other sources of measurement uncertainty were
      minor. Results on certified reference materials agreed within 1% of the certified
      values. CONCLUSIONS: An ID/LC/MS method for serum cholesterol has been developed.
      The method is simple and accurate and may be used as a candidate reference
      method.

PMID- 21175379
TI  - Miniaturization and globalization of clinical laboratory activities.
AB  - Clinical laboratories provide an invaluable service to millions of people around
      the world in the form of quality diagnostic care. Within the clinical laboratory
      industry the impetus for change has come from technological development
      (miniaturization, nanotechnology, and their collective effect on point-of-care
      testing; POCT) and the increasingly global nature of laboratory services.
      Potential technological gains in POCT include: the development of bio-sensors,
      microarrays, genetics and proteomics testing, and enhanced web connectivity. In
      globalization, prospective opportunities lie in: medical tourism, the migration
      of healthcare workers, cross-border delivery of testing, and the establishment of
      accredited laboratories in previously unexplored markets. Accompanying these
      impressive opportunities are equally imposing challenges. Difficulty
      transitioning from research to clinical use, poor infrastructure in developing
      countries, cultural differences and national barriers to global trade are only a
      few examples. Dealing with the issues presented by globalization and the impact
      of developing technology on POCT, and on the clinical laboratory services
      industry in general, will be a daunting task. Despite such concerns, with
      appropriate countermeasures it will be possible to address the challenges posed.
      Future laboratory success will be largely dependent on one's ability to adapt in
      this perpetually shifting landscape.

PMID- 21175380
TI  - Age-related macular degeneration: genetic and clinical findings.
AB  - Age-related macular degeneration (AMD) is a sight threatening eye disease that
      affects millions of humans over the age of 65 years. It is considered to be the
      major cause of irreversible blindness in the elderly population in the developed
      world. The disease is prevalent in Europe and the United States, which has a
      large number of individuals of European descent. AMD is characterized by a
      progressive loss of central vision attributable to degenerative and neovascular
      changes that occur in the interface between the neural retina and the underlying
      choroid. This location contains the retinal photoreceptors, the retinal pigmented
      epithelium, a basement membrane complex known as Bruch's membrane and a network
      of choroidal capillaries. AMD is increasingly recognized as a complex genetic
      disorder where one or more genes contribute to an individual's susceptibility to
      development of the condition, while the prevailing view is that the disease stems
      from the interaction of multiple genetic and environmental factors. Although it
      has been proposed that a threshold event occurs during normal aging, the sequelae
      of biochemical, cellular, and molecular events leading to AMD are not fully
      understood. Here, we review the clinical aspects of AMD and summarize the genes
      which have been reported to have a positive association with the disease.

PMID- 21175381
TI  - BRAF analysis by fine needle aspiration biopsy of thyroid nodules improves
      preoperative identification of papillary thyroid carcinoma and represents a
      prognostic factor. A mono-institutional experience.
AB  - BACKGROUND: The current preoperative diagnosis of a thyroid mass relies on
      microscopic evaluation of thyroid cells obtained by fine needle aspiration biopsy
      (FNAB). More recently, FNAB has been combined with molecular analysis to increase
      the accuracy of the cytological evaluation. In this mono-institutional
      prospective study, we evaluated whether the routine introduction of BRAF testing
      in thyroid FNAB could help ameliorate the preoperative recognition of papillary
      thyroid carcinoma (PTC) in "suspended" or malignant cytological categories.
      Moreover, we investigated the prognostic role of the BRAFV600E mutation in PTC.
      METHODS: BRAFV600E analysis was performed in thyroid FNAB from 270 patients
      classified into one of five cytological categories THY1, THY2, THY3, THY4, THY5.
      All subsequently underwent thyroidectomy+/-node dissection, from October 2008 to
      September 2009 in our Department. For each cytological category, we considered
      the definitive histological diagnosis of PTC and the presence of the BRAFV600E
      mutation. In 141 patients with a final tissue diagnosis of PTC, we correlated the
      presence of BRAFV600E with gender, age, histotype, TNM, size of the lesion,
      extracapsular extension, node metastases and multifocality. RESULTS: The
      prevalence of the BRAFV600E mutation, among PTCs at final tissue diagnosis, was
      69%. It improved the FNAB diagnostic accuracy from 88% to 91%. The BRAFV600E
      mutation was correlated with older age, classical variant of PTC, advanced stages
      in patients > 45 years. CONCLUSIONS: BRAFV600E testing could play a role in
      improving the diagnostic accuracy of FNAB for PTC, representing a useful adjuvant
      tool in presurgical characterization of thyroid nodes in particular cases. There
      is an association between the BRAFV600E mutation and some clinico-pathological
      characteristics of PTC.

PMID- 21175382
TI  - Platelet function testing in hirudin and BAPA anticoagulated blood.
AB  - BACKGROUND: Sodium citrate is the most commonly used anticoagulant for platelet
      function testing. However, the use of citrated blood for platelet function
      analysis has been criticized due to creation of a non-physiological milieu.
      Moreover, platelet function measurements performed with citrated blood need to be
      completed within 4 h after blood collection. Alternatively, hirudin and recently,
      a dual thrombin/factor Xa inhibitor benzylsulfonyl-D-Arg-Pro-4-amidinobenzylamide
      (BAPA), can be used to improve the reactivity after prolonged storage of
      platelets. The present study investigated platelet function tests using hirudin
      and BAPA anticoagulated blood. METHODS: Blood was obtained from 30 healthy
      individuals and 20 patients on aspirin or clopidogrel therapy, and stored for 2,
      12, 24 or 48 h. Light transmission aggregometry and impedance platelet
      aggregometry were performed using adenosine 5-diphosphate (ADP) and arachidonic
      acid as agonists. The vasodilator stimulated phosphoprotein (VASP)
      phosphorylation assay was evaluated. RESULTS: Platelet aggregation measurements
      of healthy individuals and patients showed stable platelet aggregation values
      induced by arachidonic acid, after 24 h, when hirudin or BAPA anticoagulated
      blood was used. However, citrated blood resulted in significantly reduced
      platelet response after 12 h. ADP-induced light transmission aggregation of
      healthy individuals and patients exhibited unchanged platelet aggregation after
      12 h using hirudin or BAPA anticoagulated blood, while significantly reduced
      platelet response was observed after 12 h when using citrated blood. In contrast,
      measurement of ADP-induced aggregation by use of impedance aggregometry resulted
      in reduced stability over 12 h using hirudin or BAPA anticoagulated blood. The
      VASP assay exhibited no significant changes in results over a storage period of
      48 h, independent of the anticoagulants used. CONCLUSIONS: Use of hirudin or BAPA
      anticoagulated blood resulted in improvement of stability of platelet function
      measurements.

PMID- 21175383
TI  - Is there a link between a high-fat diet during puberty and breast cancer risk?

PMID- 21175385
TI  - Ulipristal acetate: a new emergency contraceptive that is safe and more effective
      than levonorgestrel.
AB  - Ulipristal acetate (UPA), a selective progesterone receptor modulator, when taken
      as a single 30-mg dose, is safe and effective for emergency contraception up to 5
      days (120 h) following unprotected intercourse. This indication has been approved
      in Europe since May 2009 and was approved by the US FDA in August 2010. The older
      progesterone-only emergency contraceptive, levonorgestrel (LNG), is approved only
      up to 72 h after unprotected intercourse. UPA is effective in delaying or
      inhibiting ovulation, even if taken 24 to 48 h prior to expected ovulation, a
      time when LNG is no longer effective. A recent meta-analysis of two randomized
      clinical trials showed UPA to have a pregnancy risk 42% lower than LNG up to 72
      h, and 65% lower in the first 24 h following unprotected intercourse. In a
      randomized trial enrolling women up to 5 days after unprotected intercourse,
      significantly more pregnancies were prevented with UPA than with LNG when taken
      beyond 72 h.

PMID- 21175386
TI  - Drospirenone/ethinylestradiol: a review on efficacy and noncontraceptive
      benefits.
AB  - Considerable advances have been made in the field of combined oral contraceptives
      since their introduction 50 years ago. This ongoing evolution has been focused on
      reducing the estrogen dose and synthesizing new progestogens. A recently launched
      combination of ethinylestradiol 20 ug and drospirenone 3 mg demonstrates the
      advantages of a lower estrogen dose with the antimineralocorticoid activity of
      drospirenone that is responsible for the drug's significant antiandrogenic and
      antimineralocorticoid effects, reflected clinically in lower rates of adverse
      events including less fluid retention. In addition to the drug's contraceptive
      efficacy, its effects on the skin and other classic noncontraceptive benefits,
      the ethinylestradiol 20 ug and drospirenone 3 mg combination has demonstrated
      highly satisfactory results in women with premenstrual dysphoric syndrome.

PMID- 21175388
TI  - The current status of lymphadenectomy in the management of endometrial cancer.
AB  - The International Gynocologic Cancer Society is a biannual meeting for those
      multidiscipline physicians who are involved in research and the clinical care of
      women with a gynecologic cancer. Approximately 3000 physicians from all
      geographic areas attended and heard presentations covering all aspects of
      gynecologic cancer.

PMID- 21175389
TI  - Preoperative evaluation of adnexal masses.
AB  - This is a large multicenter trial designed to determine the efficacy of second
      stage diagnostic testing when the primary diagnostic test has provided an
      uncertain diagnosis of a benign or malignant adnexal mass. Women with adnexal
      masses were evaluated using ultrasonography. Clinical and ultrasonographic data
      were employed to determine the risk of malignancy using 11 statistical models and
      their performance was evaluated based on histologic findings at surgery. Overall,
      the ultrasound examiner's subjective evaluation had the highest area under the
      curve and specificity, with respect to diagnostic performance. Of the
      mathematical models evaluated, LR1 performed the best, with an area under the
      curve of 0.95, a sensitivity of 92% and a specificity of 84%. The accuracy of
      subjective evaluation did not improve with the addition of any second stage test.
      If the LR1 model was used as the primary diagnostic test, the addition of
      subjective evaluation as a secondary test was found to be beneficial.

PMID- 21175390
TI  - A new TNM classification for breast cancer to meet the demands of the present and
      the challenges of the future.
AB  - In this article we will describe our proposed changes to the breast cancer tumour
      nodal metastasis (TNM) classification which, while retaining TNM structure to
      ensure compatibility is retained, will render it more useful and better able to
      accommodate future developments. We propose changing T to specify exact tumor
      size (a tumor of pathological diameter 1.7 cm would be pT1.7); changing N to
      specify the number of metastatic lymph nodes over the total number removed (e.g.,
      pN5/21); adding suffixes to M to indicate metastatic site; removing in situ
      neoplasms from the classification, since they are not carcinomas and are
      incapable of metastasizing; and removing the terms 'infiltrating' and 'invasive'
      since they are redundant. Finally, we would include hormone receptor, HER2, and
      other biological indicators of prognosis, as they are verified, in a placeholder
      system appended to the TNM. These proposals shift the emphasis from the quantity
      of tumor present to the quality of the cancer.

PMID- 21175391
TI  - Use of mifepristone to treat endometriosis: a review of clinical trials and trial
      like studies conducted in China.
AB  - China was the first country in the world that approved mifepristone (RU-486) for
      abortion. A total of 6 years after the report published in the Western world
      indicated that mifepristone may also be effective in treating endometriosis, the
      first paper on the same topic was published in China in 1997. Since then, over
      160 studies on this topic have been published in China. We retrieved 104 papers
      on clinical trials and trial-like studies conducted in China evaluating the use
      of mifepristone to treat endometriosis that were published in the last 11 years.
      We found that the quality of these studies is well below an acceptable level,
      making it difficult to judge whether mifepristone is truly efficacious. There are
      intriguing signs that these studies, as a whole, have serious anomalies. The
      areas that are glaringly deficient are informed consent, choice of outcome
      measures, the evaluation of outcome measures, data analysis and randomization.
      The uniformly low quality is disquieting, given the large quantity of studies,
      the enormous amount of resource and energy put into these studies and, above all,
      the weighty issue of treatment efficacy that concerns each and every patient with
      endometriosis. Equally disquieting are the low-quality repetition, the absence of
      a critical, systematic review on the subject, the lack of suggestions for
      multicenter clinical trials and the seemingly unnecessary duplication of clinical
      trials without due informed consent. In view of this, it may be time to institute
      changes in attitude and practice, and to change education and training programs
      in the methodology of clinical trials in obstetrics and gynecology research in
      China.

PMID- 21175392
TI  - Menopause and mental well-being: timing of symptoms and timing of hormone
      treatment.
AB  - In the aftermath of the Women's Health Initiative studies, both the clinical and
      basic science communities had to sort out divergent results among experimental
      findings, observational data and randomized controlled trials in order to
      establish a shared analysis. The scientific community formally debates the role
      of different HRT formulations, hormone doses, time of treatment initiation since
      the menopause and the age of treated women. Basic scientists demonstrated that
      the multiple neuroprotective effects of estrogen on brain cells may induce a
      differential biological response according to the time of treatment. Progesterone
      (but not all synthetic progestins) also has pivotal neuroactive functions in
      animal models of reproductive aging. Additionally, epidemiological surveys
      provide information regarding the detrimental role of hypogonadism on mental well
      being. The present article briefly summarizes current evidence supporting the
      neuroactive role of estrogen, with reference to the clinical finding sustaining
      the intriguing hypothesis of the early female brain senescence as a highly
      responsive period to estrogen treatment.

PMID- 21175394
TI  - Hypoactive Sexual Desire Disorder and current pharmacotherapeutic options in
      women.
AB  - Hypoactive Sexual Desire Disorder (HSDD) is the most common female sexual
      dysfunction. The diagnosis of HSDD requires the existence of personal distress or
      interpersonal difficulties associated with low sexual desire, that cannot be
      explained by any other psychiatric affection and that is not exclusively due to a
      disease or substance. HSDD can have a serious effect on emotional wellbeing and
      interpersonal relationships, and it occurs in premenopausal and postmenopausal
      women. The Decreased Sexual Desire Screener is a shortened diagnostic method
      designed to help doctors who are not specialized in female sexual dysfunction to
      diagnose acquired HSDD in women. There is evidence that treatment with androgens
      or with estrogens is effective in HSDD; however, important unanswered questions
      still exist. Presently, new therapeutic strategies to combat HSDD are being
      researched, including novel methods of testosterone provision and drugs that act
      upon the CNS.

PMID- 21175395
TI  - Vaccination in pregnancy.
AB  - Vaccination is one of the most effective strategies employed to prevent morbidity
      and mortality from infectious diseases. Pregnancy is considered to be a time when
      women have consistent contact with their healthcare providers and it presents an
      opportunity for providers to review their immunization status and to advocate for
      appropriate vaccination antepartum and in the immediate postpartum period. All
      forms of immunization, with the exception of live viral or live bacterial
      vaccines are generally considered to be safe for administration during pregnancy.
      It is important that healthcare providers counsel pregnant women about the
      benefits of receiving the vaccines that are recommended during pregnancy as well
      as the potential risks to the developing fetus. It is imperative that
      obstetricians and primary care providers are aware of and implement the
      vaccination guidelines for women, both during pregnancy and in the postpartum
      period.

PMID- 21175393
TI  - Gonadal hormones and cognitive aging: a midlife perspective.
AB  - Gonadal steroids affect a variety of brain processes. Cognitive consequences of
      hormonal changes associated with menopause are of scientific interest and of
      relevance to public health. Natural menopause is a normal physiological process
      that can only be directly studied through observational research. Similarly,
      surgical menopause in humans is rarely directly amenable to experimental
      research. Causality with respect to cognitive outcomes is, therefore, difficult
      to infer. Cross-sectional and longitudinal findings from the Melbourne Women's
      Midlife Health Project, the Study of Women's Health Across the Nation and other
      midlife cohorts suggest that cognitive consequences of the natural menopausal
      transition are probably small, at least during midlife and at least for episodic
      memory, which is a key cognitive domain. The data for episodic memory are the
      most robust. Midlife episodic memory performance is similar both shortly before
      and after natural menopause, and serum estradiol concentration in midlife is not
      associated with episodic memory performance. Effects of natural menopause on
      other cognitive domains, cognitive consequences of surgical menopause and late
      life cognitive consequences of midlife hormonal exposures are less well
      understood and merit continued study.

PMID- 21175396
TI  - The prevention of cervical cancer in Africa.
AB  - In this article we aim to draw attention to the burden of cervical cancer in
      Africa for reproductive health and review strategies for prevention, including
      appropriate noncytology-based cervical screening and prophylactic human
      papillomavirus vaccination. We consider the heavy burden of disease attributable
      to human papillomavirus infection borne by developing countries, particularly in
      Africa. Following identification of the human papillomavirus as the infectious
      etiological agent and elucidation of the long natural history of cervical
      neoplasia, cervical cancer is now one of the most preventable of all cancers.
      Opportunities for primary prevention by prophylactic vaccination and secondary
      prevention by appropriate cervical screening are discussed, together with the
      importance of population coverage. Qualitative work on attitudes towards cervical
      cancer prevention, education needs, the creation of an environment for informed
      choice and uptake are essential aspects of effective prevention programs.
      Cervical cancer poses a huge health burden in Africa. It is a disease that is
      eminently preventable given political will, the availability of affordable
      vaccines, appropriate cervical screening and access to cheap, point-of-care human
      papillomavirus testing. There are a number of unanswered questions for the
      prevention of cervical cancer and a need for demonstration projects to address
      these and further develop prevention strategies.

PMID- 21175398
TI  - Chemical characterization of various fractions of leaves of Cinnamomum tamala
      Linn toward their antioxidant, hypoglycemic, and anti-inflammatory property.
AB  - Cinnamomum tamala (CT) Linn. (Lauraceae) is a component of Indian spices and is
      also used as antidiabetic agent. Its antioxidant potential was reported by other
      authors and recently our group has reported its immune-suppressive property.
      Here, CT leaves were extracted with methanol (CTT) and also with various organic
      solvents of increasing polarity such as hexane (CTH), ethyl acetate (CTEA), and
      methanol (CTE) in successive manner by continuous Soxhlet extractor. The active
      compounds of CTT and CTH were analyzed by GC-MS and most abundant compound
      (eugenol) was further analyzed by HPLC. These extracts were tested for their free
      radical (FR) scavenging potential for different FR species, hypoglycemic
      potential on alloxan-induced hyperglycemia, and anti-inflammatory property in
      carrageenan-induced paw edema and lipopolysaccharide (LPS)-induced nitric oxide
      (NO) production in rat peritoneal macrophage culture. Result showed that CTH was
      the most active fraction toward these parameters, which was parallel to its
      eugenol and total phenolic content concentration.

PMID- 21175400
TI  - Models for thermal damage in tissues: processes and applications.
AB  - Irreversible thermal alterations in tissue function and structure are used in
      clinical applications to achieve diverse goals, from lower-temperature tumor
      ablation to higher-temperature tissue fusion and surgical cutting. The typical
      formulation in tumor hyperthermia studies, the thermal iso-effect dose, derives
      from cell-survival studies but describes a single process only over a limited
      range of temperatures and is thus not suitable for multiple higher-temperature
      events. Many other thermal damage processes have been described using the
      Arrhenius kinetic rate of formation approach, which has the advantage that it is
      inherently quantitative in nature and can easily be compared with quantitative
      markers of injury or histologic section. The vast majority of Arrhenius studies
      have been directed toward measurable cellular effects at relatively low
      temperatures. Some emphasis in this paper has been placed on what is known of
      higher-temperature processes to support the theme of this issue. This review
      compares and contrasts the two thermal-damage formulations and reviews methods to
      convert between them.

PMID- 21175399
TI  - Modulation of ABCA1 by an LXR agonist reduces beta-amyloid levels and improves
      outcome after traumatic brain injury.
AB  - Traumatic brain injury (TBI) increases brain beta-amyloid (Abeta) in humans and
      animals. Although the role of Abeta in the injury cascade is unknown, multiple
      preclinical studies have demonstrated a correlation between reduced Abeta and
      improved outcome. Therefore, therapeutic strategies that enhance Abeta clearance
      may be beneficial after TBI. Increased levels of ATP-binding cassette A1 (ABCA1)
      transporters can enhance Abeta clearance through an apolipoprotein E (apoE)
      mediated pathway. By measuring Abeta and ABCA1 after experimental TBI in C57BL/6J
      mice, we found that Abeta peaked early after injury (1-3 days), whereas ABCA1 had
      a delayed response (beginning at 3 days). As ABCA1 levels increased, Abeta levels
      returned to baseline levels-consistent with the known role of ABCA1 in Abeta
      clearance. To test if enhancing ABCA1 levels could block TBI-induced Abeta, we
      treated TBI mice with the liver X-receptor (LXR) agonist T0901317. Pre- and post
      injury treatment increased ABCA1 levels at 24 h post-injury, and reduced the TBI
      induced increase in Abeta. This reduction in Abeta was not due to decreased
      amyloid precursor protein processing, or a shift in the solubility of Abeta,
      indicating enhanced clearance. T0901317 also limited motor coordination deficits
      in injured mice and reduced brain lesion volume. These data indicate that
      activation of LXR can reduce Abeta accumulation after TBI, and is accompanied by
      improved functional recovery.

PMID- 21175401
TI  - Mathematical modeling of thermal ablation.
AB  - Ablation techniques have become a widespread choice for the treatment of
      cancerous tumors for which surgical resection techniques have a poor prognosis.
      The minimally invasive nature and high success rate when performed by experienced
      clinicians mean that ablation is likely to remain a core technique. However, the
      success rate can drop off dramatically when less-experienced operators are
      involved, and it is particularly difficult to kill all of the tumor and only the
      tumor, given the dynamic nature of the processes that lead to cell death.
      Mathematical modeling of the response to ablation treatment has a long history.
      Since the seminal paper of Pennes in 1948, there have been numerous attempts to
      propose models that are both physiologically accurate and computationally
      inexpensive. All of these models are based on different principles and
      assumptions, which may make them suitable only for particular applications. This
      makes choosing a model very difficult because of the lack of understanding about
      what the limitations of different assumptions are likely to be and how this
      influences the necessary computational resources. Here we review the models
      available in the literature, illustrating how the different assumptions impact
      upon both their accuracy and computational expense.The primary intentions are to
      provide a critical scientific review and a practical guide for researchers
      wishing to use such models in clinical applications.

PMID- 21175402
TI  - State of the art in computer-assisted planning, intervention, and assessment of
      liver-tumor ablation.
AB  - Percutaneous, image-guided thermal tumor ablation procedures are used
      increasingly for minimally invasive, local treatment of tumors in the liver. The
      planning of these procedures; the support of targeting, monitoring, and
      controlling during the intervention itself; and the assessment of the treatment
      response can all benefit significantly from computer assistance. The outcome can
      be optimized by supporting the physician in the process of determining an
      intervention strategy that enables complete destruction of the targeted tumor
      while reducing the danger of complications. During the intervention, computer
      assisted methods can be used to guide the physician in the implementation of the
      intended strategy by providing planning information. Assessment of the
      intervention result is carried out by comparison of the achieved coagulation with
      the target tumor volume. Supporting this comparison facilitates the early
      detection of potential recurrences. This report provides an overview of state-of
      the-art computer-assisted methods for the support of thermal tumor ablations in
      the liver. Proper approaches for image segmentation, access-path determination,
      simulation, visualization, interventional guidance, and post-interventional
      assessment, as well as integrated work flow-oriented solutions, are reviewed with
      respect to technical aspects and applicability in the clinical setting.

PMID- 21175403
TI  - Biophysics of radiofrequency ablation.
AB  - Radiofrequency (RF) ablation is a treatment modality that kills unwanted tissue
      by heat. Starting with cardiac arrhythmia treatment in the 1980s, RF ablation has
      found clinical application in a number of diseases, and is now the treatment of
      choice for certain types of cardiac arrhythmia and certain cancers. During RF
      ablation, an electrode is inserted into or steered intravascularly to the target
      tissue region under medical imaging guidance. Then, a tissue volume surrounding
      the electrode is destroyed by heating via RF electric current. This paper reviews
      the biophysics of tissue heating during RF ablation. Effects of electrical tissue
      conductivity and its change with temperature are discussed. Procedures and
      devices specific for cancer treatment and for arrhythmia treatment are presented
      with a brief discussion of additional clinical applications.

PMID- 21175405
TI  - Laser-induced thermal therapy for tumor ablation.
AB  - Image-guided ablation of tumors is assuming an increasingly important role in
      many oncology services as a minimally invasive alternative to conventional
      surgical interventions for patients who are not good candidates for surgery.
      Laser-induced thermal therapy (LITT) is a percutaneous tumor-ablation technique
      that utilizes high-power lasers placed interstitially in the tumor to deliver
      therapy. Multiple laser fibers can be placed into the treatment volume and,
      unlike other interstitial heating techniques, can be fired simultaneously to
      rapidly treat large volumes of tissue. Modern systems utilize small, compact,
      high-power laser diode systems with actively cooled applicators to help keep
      tissue from charring during procedures. Additionally, because this approach to
      thermal therapy is easily made magnetic resonance (MR) compatible, the
      incorporation of magnetic resonance imaging (MRI) for treatment planning,
      targeting, monitoring, and verification has helped to expand the number of
      applications in which LITT can be applied safely and effectively. We provide an
      overview of the clinically used technology and algorithms that provide the
      foundations for current state-of-the-art MR-guided LITT (MRgLITT), including
      procedures in the brain, liver, bone, and prostate as examples. In addition to
      advances in imaging and delivery, such as the incorporation of nanotechnology,
      next-generation MRgLITT systems are anticipated to incorporate an increasing
      presence of in silico-based modeling of MRgLITT procedures to provide human
      assisted computational tools for planning, MR model-assisted temperature
      monitoring, thermal-dose assessment, and optimal control.

PMID- 21175406
TI  - A review of hyperthermia combined with radiotherapy/chemotherapy on malignant
      tumors.
AB  - Therapeutic hyperthermia is a procedure that involves heating tissues to a higher
      temperature level, typically ranging from 41 degrees C to 45 degrees C. Its
      combination with radiotherapy and/or chemotherapy has been performed for many
      years, with remarkable success in treating advanced and recurrent cancers. The
      current hyperthermia strategies generally include local, regional, and whole-body
      hyperthermia, which can be implemented by many heating methods, such as
      microwave, radiofrequency, laser, and ultrasound. There are several hyperthermic
      treatment modalities in conjunction with radiotherapy/chemotherapy. Numerous
      studies have attempted to explain the mechanisms of thermosensitization from
      radiation and chemotherapy; however, a generalized standard for determining an
      optimal hyperthermia modality combined with radiotherapy/chemotherapy has not
      been established, so more research is needed. Fortunately, phase II/III clinical
      trials have demonstrated that hyperthermia combination therapy is beneficial for
      local tumor control and survival in patients with high-risk tumors of different
      types. The aim of this article is to present a comprehensive review of the latest
      advances in tumor hyperthermia combined with radiotherapy and/ or chemotherapy.
      We specifically focus on synergistic cellular and molecular mechanisms, thermal
      dose, treatment sequence, monitoring and imaging, and clinical outcomes of the
      combination therapy. The role of nanoparticles in sensitization during radio
      /chemotherapy is also evaluated. Finally, research challenges and future trends
      in the related areas are presented.

PMID- 21175404
TI  - Microwave tissue ablation: biophysics, technology, and applications.
AB  - Microwave ablation is an emerging treatment option for many cancers, cardiac
      arrhythmias, and other medical conditions. During treatment, microwaves are
      applied directly to tissues to produce rapid temperature elevations sufficient to
      produce immediate coagulative necrosis. The engineering design criteria for each
      application differ, with individual consideration for factors such as desired
      ablation zone size, treatment duration, and procedural invasiveness. Recent
      technological developments in applicator cooling, power control, and system
      optimization for specific applications promise to increase the utilization of
      microwave ablation in the future. This article reviews the basic biophysics of
      microwave tissue heating, provides an overview of the design and operation of
      current equipment, and outlines areas for future research.

PMID- 21175407
TI  - A new perspective for stem-cell mechanobiology: biomechanical control of stem
      cell behavior and fate.
AB  - Biomechanics is known to play an important role in cell metabolism. Cell
      phenotype, tissue-specific functions, and fate critically depend on the
      extracellular mechanical environment. The mechanical properties of the cell
      itself, such as cytoskeleton elasticity, membrane tension, and adhesion strength,
      may also play an important role in cell homeostasis and differentiation.
      Pluripotent bone marrow-derived human mesenchymal stem cells, for example, can be
      differentiated into many tissue-specific lineages. While cellular biomechanical
      properties are significantly altered during stem-cell specification to a
      particular phenotype, the complexity of events associated with transformation of
      these precursor cells leaves many questions unanswered about morphological,
      structural, proteomic, and functional changes in differentiating stem cells. A
      thorough understanding of stem-cell behavior would allow the development of more
      effective approaches to the expansion of stem cells in vitro and the regulation
      of their commitment to a specific phenotype. Control of cell behaviors might be
      feasible through manipulation of the cellular biomechanical properties using
      various external physical stimuli, including electric fields, mechanical stimuli,
      and genetic manipulation of the expression of particular genes. Biomechanical
      regulation of stem-cell differentiation can greatly minimize the number of
      chemicals and growth factors that would otherwise be required for composite
      tissue engineering. Determination and the appropriate use of the known
      physicochemical cues will facilitate current research effort toward designing and
      engineering functional tissue constructs.

PMID- 21175408
TI  - Intramuscular EMG signal decomposition.
AB  - Information regarding motor unit potentials (MUPs) and motor unit fi ring
      patterns during muscle contractions is useful for physiological investigation and
      clinical examinations either for the understanding of motor control or for the
      diagnosis of neuromuscular disorders. In order to obtain such information,
      composite electromyographic (EMG) signals are decomposed (i.e., resolved into
      their constituent motor unit potential trains [MUPTs]). The goals of automatic
      decomposition techniques are to create a MUPT for each motor unit that
      contributed significant MUPs to the original composite signal. Diagnosis can then
      be facilitated by decomposing a needle-detected EMG signal, extracting features
      of MUPTs, and finally analyzing the extracted features (i.e., quantitative
      electromyography). Herein, the concepts of EMG signals and EMG signal
      decomposition techniques are explained. The steps involved with the decomposition
      of an EMG signal and the methods developed for each step, along with their
      strengths and limitations, are discussed and compared. Finally, methods developed
      to evaluate decomposition algorithms and assess the validity of the obtained
      MUPTs are reviewed and evaluated.

PMID- 21175409
TI  - A review of clinical quantitative electromyography.
AB  - Information regarding the morphology of motor unit potentials (MUPs) and motor
      unit firing patterns can be used to help diagnose, treat, and manage
      neuromuscular disorders. In a conventional electromyographic (EMG) examination, a
      clinician manually assesses the characteristics of needle-detected EMG signals
      across a number of distinct needle positions and forms an overall impression of
      the condition of the muscle. Such a subjective assessment is highly dependent on
      the skills and level of experience of the clinician, and is prone to a high error
      rate and operator bias. Quantitative methods have been developed to characterize
      MUP waveforms using statistical and probabilistic techniques that allow for
      greater objectivity and reproducibility in supporting the diagnostic process. In
      this review, quantitative EMG (QEMG) techniques ranging from simple reporting of
      numeric MUP values to interpreted muscle characterizations are presented and
      reviewed in terms of their clinical potential to improve status quo methods. QEMG
      techniques are also evaluated in terms of their suitability for use in a clinical
      decision support system based on previously established criteria. Aspects of
      prototype clinical decision support systems are then presented to illustrate some
      of the concepts of QEMG-based decision making.

PMID- 21175411
TI  - Sclerosing bone disorders: too much of a good thing.
AB  - Osteoporosis is, because of its high prevalence and morbidity, a major health
      problem in our aging population. Epidemiological studies clearly indicated a
      heritability of up to 80% for relevant bone parameters with an additional role
      for environmental factors, such as food intake and physical exercise. A major
      contribution to our current understanding of bone homeostasis is obtained by
      studying monogenic diseases with an increased bone density, the sclerosing bone
      dysplasias. Gene identifications have revealed relevant pathways and mechanisms
      both in the bone-resorbing osteoclasts and bone-forming osteoblasts. Furthermore,
      natural variants within these genes turned out to have an influence on bone
      mineral density in the general population. Finally, interesting drug targets for
      the prevention and treatment of osteoporosis were revealed. Although many major
      breakthroughs have been realized, still a huge amount of significant information
      is hidden in these pathologies as the function of many of these genes and newly
      identified pathways is not, or only partially, clear.

PMID- 21175410
TI  - Genome instability in the context of chromatin structure and fragile sites.
AB  - Genomes are exposed to various external stimuli that induce DNA damage in the
      form of single- or double-stranded DNA breaks. Fragile sites in the human genome
      are sensitive to genotoxic stress and, when not appropriately repaired, are
      responsible for chromosomal aberrations, including the gene amplifications
      observed in a variety of tumors. Moreover, when DNA lesions from different
      chromosomes are in close proximity and not repaired, the probability of
      chromosome translocations is greatly increased. These events can be induced by
      ionizing radiation that, in a majority of cells, induces a G2/M cell cycle arrest
      and is characterized by the repositioning of many tumor-related genes closer to
      the nuclear interior. On the basis of this knowledge, we review functional and
      structural aspects of chromosomal rearrangements and the DNA repair machinery.

PMID- 21175412
TI  - Bone changes and fracture related to menstrual cycles and ovulation.
AB  - Women's menstrual cycles and bone remodeling are linked in part by their co
      dependency on the stress- and resource-associated variables that govern both of
      their cyclical natures. Therefore, it is not surprising that evolution has
      resulted in the same signaling molecules and pathways that regulate normal
      ovarian function to be involved in bone remodeling and turnover. This review will
      first provide an overview of the normal menstrual cycle, its modification by age
      and ovulatory disturbances, and how it parallels bone remodeling. Epidemiological
      and clinical evidence will be presented that link bone remodeling, strength, and
      fractures with women's history of reproductive and menstrual cycle
      characteristics. This combined evidence will then be presented alongside a
      synthesis of current concepts derived from basic science investigations focused
      on understanding the molecular mechanisms underlying the influence of ovarian
      factors on bone physiology. Osteoporosis is a significant source of morbidity for
      older women. The data presented in this review suggest that a woman's
      reproductive cycle and ovulatory characteristics foreshadow the future health of
      her bones. More importantly, identifying the key mechanisms underlying
      reproductive and bone health would not only provide essential preventative
      strategies, but may also uncover attractive targets for the treatment of
      osteoporosis.

PMID- 21175413
TI  - Role of parathyroid hormone (PTH) and PTH-related protein (PTHrP) in regulating
      mineral homeostasis during fetal development.
AB  - Parathyroid hormone (PTH) and PTH-related protein (PTHrP) play complementary and
      overlapping roles in regulating fetal mineral homeostasis. PTHrP is expressed
      within the growth plate, directs endochondral bone formation, and determines the
      fate of chondrocytes before bone formation can be initiated. It is expressed in
      placenta and is present at high levels in the fetal circulation. It stimulates
      placental calcium (and possibly magnesium) transfer and raises blood mineral
      levels above ambient maternal values in order to effect mineralization of the
      skeleton. It does not upregulate in response to absence of PTH or hypocalcemia,
      and thus, its secretion may be regulated autonomously or in response to placental
      signals. PTH is expressed in fetal parathyroids and placenta. Despite circulating
      at low levels, it has a more dominant effect than PTHrP in regulating the blood
      calcium and ensuring adequate mineralization of the skeleton. It may also have
      effects on bone formation in the steps that occur after apoptosis of hypertrophic
      chondrocytes. Unlike PTHrP, it increases with fetal hypocalcemia, but its
      secretion is constrained by the calcium-sensing receptor to maintain the adult
      calcium level, well below what the fetus normally achieves. PTH also stimulates
      placental calcium transfer, and its absence disrupts placental expression of
      calciotropic and cation transporter genes.

PMID- 21175415
TI  - Modulation of innate immune responses by hantaviruses.
AB  - Hantavirus infection can cause hantavirus cardiopulmonary syndrome or hemorrhagic
      fever with renal syndrome depending on the virus species involved. The
      determinants for the virus species specific virulence in humans are unclear.
      Successful infection is a conditio sine qua non for the virulence of a virus and
      it is well-known that the innate interferon (IFN) system generally plays a
      decisive role to prevent establishment of an infection. The importance of the IFN
      system is underscored by the fact that viruses have developed an amazing number
      of different escape mechanisms to enable replication in face of the antiviral
      host response. Interestingly, pathogenic hantaviruses escape induction of innate
      antiviral responses in the early phase of the infection, which are elicited in a
      pronounced manner by nonpathogenic hantaviruses in vitro. This differential
      response might be important for the pathogenicity of hantaviruses in humans. This
      review aims to summarize the current knowledge about the interaction between
      hantaviruses and the innate IFN system. Detailed characterization of the cellular
      sensors and pathways that lead to activation of the IFN system on one side and
      the viral escape mechanisms on the other might help to develop novel vaccination
      strategies and therapeutic approaches.

PMID- 21175416
TI  - Endothelial cells as key determinants of the tumor microenvironment: interaction
      with tumor cells, extracellular matrix and immune killer cells.
AB  - Besides tumor cells, the tumor microenvironment harbors a variety of host-derived
      cells, such as endothelial cells, fibroblasts, innate and adaptive immune cells.
      It is a complex and highly dynamic environment, providing very important cues to
      tumor development and progression. Tumor-associated endothelial cells play a key
      role in this process. On the one hand, they form tumor-associated (angiogenic)
      vessels through sprouting from locally preexisting vessels or recruitment of bone
      marrow-derived endothelial progenitor cells, to provide nutritional support to
      the growing tumor. On the other hand, they are the interface between circulating
      blood cells, tumor cells and the extracellular matrix, thereby playing a central
      role in controlling leukocyte recruitment, tumor cell behavior and metastasis
      formation. Hypoxia is a critical parameter modulating the tumor microenvironment
      and endothelial/tumor cell interactions. Under hypoxic stress, tumor cells
      produce factors that promote tumor angiogenesis, tumor cell motility and
      metastasis. Among these factors, VEGF, a main angiogenesis modulator, can also
      play a critical role in the control of immune tolerance. This review discusses
      some aspects of the role of endothelial cells within tumor microenvironment and
      emphasizes their interaction with tumor cells, the extracellular matrix and with
      immune killer cells. We will also address the role played by circulating
      endothelial progenitor cells and illustrate their features and mechanism of
      recruitment to the tumor microenvironment and their role in tumor angiogenesis.

PMID- 21175417
TI  - Role of the glucocorticoid-induced TNFR-related protein (GITR)-GITR ligand
      pathway in innate and adaptive immunity.
AB  - Glucocorticoid-induced TNF receptor-related protein (GITR) is expressed in
      regulatory T cells at high levels, but is also inducible in conventional effector
      T cells after activation. Initial studies using an agonistic anti- GITR mAb
      mislead this line of research with respect to the contribution of GITR
      stimulation on the function of regulatory T cells. In fact, GITR acts as a
      costimulatory receptor for both effector and regulatory T cells by enhancing
      effector and regulatory functions, respectively. Unlike other costimulatory
      ligands, GITR ligand (GITRL) expression on mature myeloid dendritic cells (DCs)
      is extremely limited and the GITR-GITRL pathway does not contribute markedly to
      direct interactions with T cells and antigen-presenting cells in the secondary
      lymphoid tissues. Rather, GITRL is constitutively expressed on parenchymal tissue
      cells and interacts with GITR expressed on tissue-infiltrating macrophages and
      DCs, or effector and regulatory T cells. Interactions with GITR and GITRL at
      local inflammatory sites induce site-specific production of cytokines and
      chemokines, resulting in control activation of tissue-infiltrating effector or
      regulatory cells and their migration. This review summarizes recent reports on
      the GITR-GITRL pathway, which controls both innate and adaptive immune responses.

PMID- 21175418
TI  - IL-21 is an immune activator that also mediates suppression via IL-10.
AB  - Interleukin-21 (IL-21) is a pleiotropic type I cytokine that is produced
      predominantly by CD4(+) T cells and natural killer T (NKT) cells. Although IL-21
      production is relatively restricted to these two populations of immune cells, its
      targets are numerous, including multiple lympho-hematopoietic as well as non
      hematopoietic lineages. The effects of IL-21 are specific not only to the target
      cell type, but also depend on the developmental stage of the target cell as well
      as the available co-stimulatory signals. Accordingly, IL-21 functions not only as
      a strong inducer of differentiation and proliferation but also as a pro-apoptotic
      factor. Although most of the effects of IL-21 are immunostimulatory, it has
      become clear that one of the cytokines that is potently induced by IL-21 in a
      number of lymphoid lineages is interleukin-10 (IL-10), one of the most
      immunosuppressive cytokines. The seemingly contradictory actions of IL-21 and IL
      10 and the consequences of their co-expression are currently being explored in
      numerous infectious models, autoimmune diseases, and tumor responses. This review
      seeks to critically evaluate the evidence concerning the regulation of IL-10 by
      IL-21 in a number of lineage subsets as well as to discuss the potential positive
      versus deleterious roles that this co-expression may play in a range of disease
      models.

PMID- 21175414
TI  - Function and regulation of retinoic acid-inducible gene-I.
AB  - Antiviral innate immunity is triggered by sensing viral nucleic acids. RIG-I
      (retinoic acid-inducible gene-I) is an intracellular molecule that responds to
      viral nucleic acids and activates downstream signaling, resulting in the
      induction of members of the type I interferon (IFN) family, which are regarded
      among the most important effectors of the innate immune system. Although RIG-I is
      expressed ubiquitously in the cytoplasm, its levels are subject to
      transcriptional and post-transcriptional regulation. RIG-I belongs to the IFN
      stimulated gene (ISG) family, but certain cells regulate its expression through
      IFN-independent mechanisms. Several lines of evidence indicate that deregulated
      RIG-I signaling is associated with autoimmune disorders. Further studies suggest
      that RIG-I has functions in addition to those directly related to its role in RNA
      sensing and host defense. We have much to learn and discover regarding this
      interesting cytoplasmic sensor so that we can capitalize on its properties for
      the treatment of viral infections, immune disorders, cancer, and perhaps other
      conditions.

PMID- 21175419
TI  - Emerging role of vesicular carriers for therapy of visceral leishmaniasis:
      conventional versus novel.
AB  - Visceral leishmaniasis (VL) is a systemic protozoan infection that infects a
      million people living in subtropical and tropical areas. Drugs are the major
      treatment available against this fatal infection. Conventional chemotherapy of VL
      involves treatment with pen- tavalent antimonials, pentamidine, paromomycin,
      miltefosine, etc., but this treatment is challenging because of the failure of
      drugs to penetrate macrophages where the parasite hides, toxic side effects, and
      drug resistance due to incomplete treatment schedules. The newer therapeutic
      approach of combination therapy employing multi-drug combinations provides
      improved treatment of VL because the combination reduces length of treatment,
      relapse, and risk of toxicity and increases the therapeutic index. Although
      considerable success has been attained using combination therapies, none has yet
      achieved commercial status. Therefore, there is an urgent need of designing
      novel, site-specific leishmanicidal drug carriers for safe and effective
      management of VL. Colloidal carriers such as liposomes, niosomes, emulsomes, and
      their engineered versions offer superior therapeutic efficacy over the
      conventional treatment in terms of site-specific drug delivery related to
      absolute treatment of disease with reduced side effects and toxicity. The control
      over spatial and sequential distribution of drug molecules after systemic or
      localized administration represents the major dispute in drug-delivery systems,
      and this can be resolved by the use of these colloidal carriers. The present
      review describes current conventional and combination drug therapies with special
      consideration given to the emerging role of novel vesicular colloidal carriers
      designed against VL. Colloidal carriers employing drugs in combination could lead
      to reductions in the duration of conventional treatment, better patient
      compliance, and the prevention of anti-leishmanial drug resistance or toxicity.

PMID- 21175420
TI  - Microencapsulation: an acclaimed novel drug-delivery system for NSAIDs in
      arthritis.
AB  - Arthritis refers to different medical conditions associated with disorders of the
      primary structures that determine joint functioning, such as bones, cartilage,
      and synovial membranes. Drug discovery and delivery to retard the degeneration of
      joint tissues are challenging. Current treatment of different types of arthritis
      such as osteoarthritis, rheumatoid arthritis, septic arthritis, juvenile
      idiopathic arthritis, and ankylosing spondylitis involves the administration of
      nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, diclofenac,
      aceclofenac, ibuprofen, flurbiprofen, indomethacin piroxicam, dexibuprofen,
      ketoprofen, nabumetone, nimesulide, and naproxen, mainly by the oral, parenteral,
      or topical route. However, the frequent dosing that is required with NSAIDs often
      leads to patient noncompliance, so drug-delivery technologies should be developed
      to reduce the frequency of dosing and to allow sustained release of medications.
      Microencapsulation is one of the novel drug-delivery technologies employed to
      sustain drug release. This method reduces dosing and eliminates gastrointestinal
      irritation, thus ultimately improving patient compliance in the pharmacotherapy
      of arthritis. We provide a comprehensive overview of several microencapsulation
      technologies used in the treatment of arthritis that may reduce the dose-related
      adverse effects caused by NSAIDs.

PMID- 21175421
TI  - GMP production of gene and cell therapy therapeutics.

PMID- 21175422
TI  - Synthesis, testing and structure-activity studies on a library of 5-HT4 ligands.
AB  - Several indole derivatives and analogues comprising a range of related structural
      classes were designed, synthesized and tested as ligands for the 5-HT4 receptor.
      Within each series, binding experiments showed compounds with good affinity
      demonstrating high percentage displacement values at 1 uM. The most potent of
      these (20) had a pKi of 8.54 demonstrating very good affinity. These indole
      analogues were combined with 55 ligands that were previously produced in our
      laboratory to explore the structure-activity relationships of these 5-HT4
      ligands. A CoMFA (Comparative Molecular Field Analysis) analysis was used to
      extend an earlier simple pharmacophore to suggest two new molecular features
      beyond the primary amino binding site. The pharmacophore confirmed that a newly
      described tetrahydroquinoline analogue was able to match the basic requirements
      of the model and the pharmacology of this molecule is provided in more detail.

PMID- 21175424
TI  - NADPH and iron may have an important role in attenuated mucosal defense in
      Helicobacter pylori infection?
AB  - Host intracellular iron has been recognized as an important cofactor in induction
      of nicotinamide adenine dinucleotide phosphate (NADPH)-dependent oxidative burst
      as antimicrobial defense mechanism. It is plausible that iron chelator directly
      inactivates NADPH oxidase by chelating the active site heme iron of
      flavocytochrome b558 thus blocking the transfer of electrons from NADPH to oxygen
      and its reduction to superoxide anion. Thus, altering the equilibrium of
      intracellular iron could influence the course of infection to the enhancement of
      the pathogen with regard to oxidative stress.

PMID- 21175423
TI  - Histamine H4 receptor: a novel therapeutic target for immune and allergic
      responses.
AB  - HIstamine is a biomolecular compound located in various parts of body. It
      participated in various important cellular activities associated with allergy and
      asthma. This magic bio-molecule is directly and indirectly involved in various
      biochemical reactions through G-protein couple receptors. Various histamine
      receptors and their unexplored biochemical activities attracted many biologists
      in last few decades. A surprising discovery of histamine H(4) receptor was done
      when scientist worked on histamine H(3) receptor in brain cells. The binding
      pocket of histamine H(4) differs by transmembrane domains (TM3, TM5 and TM6) from
      histamine H(3)-sub type. In this review, we enlightened various functions of
      histamine H(4) and use of histamine H(4) receptor antagonists in autoimmune
      diseases, allergic responses, inflammatory responses, and in superoxide
      generation which are helpful to establish H(4) receptor antagonists as newer anti
      histamines.

PMID- 21175425
TI  - Inhibitors from natural products to HIV-1 reverse transcriptase, protease and
      integrase.
AB  - Acquired immunodeficiency syndrome (AIDS), caused by human immunodeficiency virus
      type 1 (HIV-1) infection, is still one of the most challenging diseases of the
      early 21st century. Reverse transcriptase (RT), protease (PR) and integrase (IN)
      are three key enzymes of HIV-1. Despite the shortcomings of chemical drugs such
      as toxicity, lack of curative and multiple effects, the search for more and
      better anti-HIV agents has been focused on natural products. Many natural
      products have been shown to possess promising activities that could assist in the
      prevention and amelioration of the disease. Most of these natural anti-HIV agents
      have other medicinal values as well, which afford them further prospective as
      novel lead compounds for the development of new drugs. These natural products can
      deal with both the virus and the various disorders that are caused by HIV. In
      this review, natural inhibitors of RT, PR and IN have been found to be classified
      and the relationship between structure and inhibitory activity is discussed.

PMID- 21175426
TI  - Crystal structure of unliganded TRAP: implications for dynamic allostery.
AB  - Allostery is vital to the function of many proteins. In some cases, rather than a
      direct steric effect, mutual modulation of ligand binding at spatially separated
      sites may be achieved through a change in protein dynamics. Thus changes in
      vibrational modes of the protein, rather than conformational changes, allow
      different ligand sites to communicate. Evidence for such an effect has been found
      in TRAP (trp RNA-binding attenuation protein), a regulatory protein found in
      species of Bacillus. TRAP is part of a feedback system to modulate expression of
      the trp operon, which carries genes involved in tryptophan synthesis. Negative
      feedback is thought to depend on binding of tryptophan-bound, but not unbound,
      TRAP to a specific mRNA leader sequence. We find that, contrary to expectations,
      at low temperatures TRAP is able to bind RNA in the absence of tryptophan, and
      that this effect is particularly strong in the case of Bacillus
      stearothermophilus TRAP. We have solved the crystal structure of this protein
      with no tryptophan bound, and find that much of the structure shows little
      deviation from the tryptophan-bound form. These data support the idea that
      tryptophan may exert its effect on RNA binding by TRAP through dynamic and not
      structural changes, and that tryptophan binding may be mimicked by low
      temperature.

PMID- 21175427
TI  - Visualization of retrovirus uptake and delivery into acidic endosomes.
AB  - Diverse enveloped viruses enter cells by endocytosis and fusion with
      intracellular compartments. Recent evidence suggests that HIV also infects
      permissive cell lines by fusing with endosomes in a pH-independent manner. This
      finding highlights the importance of time-resolved monitoring of viral uptake. In
      the present study, we designed an imaging-based assay to measure endocytosis in
      real-time through probing the virus' accessibility to external solutions.
      Exposure of viruses bearing a pH-sensitive GFP (green fluorescent protein)
      variant on their surface to solutions of different acidity altered the
      fluorescence of surface-accessible particles, but not internalized viruses. By
      sequentially applying acidic and alkaline buffers with or without ammonium
      chloride, we were able to quantify the fractions of internalized and non
      internalized virions, as well as the fraction of detached particles, over time.
      The exact time of single-virus internalization was assessed from the point when a
      particle ceased to respond to a perfusion with alternating acidic and alkaline
      buffers. We found that, surprisingly, HIV pseudoparticles entered acidic
      compartments shortly after internalization. These results suggest that the virus
      might be sorted to a quickly maturing pool of endocytic vesicles and thus be
      trafficked to fusion-permissive sites near the cell nucleus.

PMID- 21175428
TI  - Involvement of miR-30c and miR-301a in immediate induction of plasminogen
      activator inhibitor-1 by placental growth factor in human pulmonary endothelial
      cells.
AB  - PAI-1 (plasminogen activator inhibitor-1) is a key physiological inhibitor of
      fibrinolysis. Previously, we have reported PlGF (placental growth factor)
      mediated transcriptional up-regulation of PAI-1 (SERPINE1) mRNA expression via
      activation of HIF-1alpha (hypoxia-inducible factor-1alpha) and AP-1 (activator
      protein-1) in HPMVECs (human pulmonary microvascular endothelial cells), which
      resulted in elevated PAI-1 in humans with SCA (sickle cell anaemia). In the
      present study, we have identified the role of post-transcriptional mechanism(s)
      of PlGF-mediated accumulation of PAI-1 mRNA in HPMVECs by examining the role of
      microRNAs (miRNAs/miRs) in PlGF-induced PAI-1 mRNA stability. Our results show
      reduced expression of miR-30c and miR-301a, but not of miR-99a, in response to
      PlGF, which have evolutionarily conserved binding sites in the 3'-UTR (3'
      untranslated region) of PAI-1 mRNA. Transfection of anti-miR-30c or anti-miR-301a
      oligonucleotides resulted in increased PAI-1 mRNA levels, which were increased
      further with PlGF stimulation. Conversely, overexpression of pre-miR-30c or pre
      miR-301a resulted in an attenuation of PlGF-induced PAI-1 mRNA and protein
      levels. Luciferase reporter assays using wild-type and mutant 3'-UTR constructs
      confirmed that the PAI-1 3'-UTR is indeed a direct target of miR-30c and miR
      301a. Finally, plasma levels of miR-30c and miR-301a were significantly down
      regulated in patients with SCA compared with normal controls. These results
      provide a post-transcriptional regulatory mechanism of PlGF-induced PAI-1
      elevation.

PMID- 21175429
TI  - For a PDK1 inhibitor, the substrate matters.
AB  - More than 20 protein kinases are directly activated by 3-phosphoinositide
      dependent kinase 1 (PDK1), which is a central component of the pathways that
      regulate cell growth, proliferation and survival. Despite the importance of PDK1
      in cell signalling, highly selective PDK1 inhibitors have not been described. In
      this issue of the Biochemical Journal, Dario Alessi's group and their
      collaborators at GlaxoSmithKline report GSK2334470, a potent and selective PDK1
      inhibitor. They show that this compound blocks the phosphorylation of known PDK1
      substrates, but surprisingly find that the potency and kinetics of inhibition
      vary for different PDK1 targets. This substrate-specific inhibition has
      implications for the development of PDK1 inhibitors as drugs.

PMID- 21175431
TI  - TB domain proteins: evolutionary insights into the multifaceted roles of
      fibrillins and LTBPs.
AB  - Fibrillins and LTBPs [latent TGFbeta (transforming growth factor beta)-binding
      proteins] perform vital and complex roles in the extracellular matrix and are
      relevant to a wide range of human diseases. These proteins share a signature
      'eight cysteine' or 'TB (TGFbeta-binding protein-like)' domain that is found
      nowhere else in the human proteome, and which has been shown to mediate a variety
      of protein-protein interactions. These include covalent binding of the TGFbeta
      propeptide, and RGD-directed interactions with a repertoire of integrins. TB
      domains are found interspersed with long arrays of EGF (epidermal growth factor)
      like domains, which occur more widely in extracellular proteins, and also mediate
      binding to a large number of proteins and proteoglycans. In the present paper,
      newly available protein sequence information from a variety of sources is
      reviewed and related to published findings on the structure and function of
      fibrillins and LTBPs. These sequences give valuable insight into the evolution of
      TB domain proteins and suggest that the fibrillin domain organization emerged
      first, over 600 million years ago, prior to the divergence of Cnidaria and
      Bilateria, after which it has remained remarkably unchanged. Comparison of
      sequence features and domain organization in such a diverse group of organisms
      also provides important insights into how fibrillins and LTBPs might perform
      their roles in the extracellular matrix.

PMID- 21175432
TI  - Drug-drug interactions: is there an optimal way to study them?

PMID- 21175430
TI  - The myotubularin family of lipid phosphatases in disease and in spermatogenesis.
AB  - The MTM (myotubularin)/MTMR (myotubularin-related) protein family is comprised of
      15 lipid phosphatases, of which nine members are catalytically active. MTMs are
      known to play a fundamental role in human physiology as gene mutations can give
      rise to X-linked myotubular myopathy or Charcot-Marie-Tooth disease, which
      manifest in skeletal muscle or in peripheral neurons respectively. Interestingly,
      studies have shown MTMR2 and MTMR5, two MTM family members, to be highly
      expressed in the testis, particularly in Sertoli and germ cells, and knockout of
      either gene resulted in spermatogenic defects. Other studies have shown that
      MTMR2 functions in endocytosis and membrane trafficking. In the testis, MTMR2
      interacts and co-localizes with c-Src/phospho-Src-(Tyr416), a non-receptor
      protein tyrosine kinase that regulates the phosphorylation state of proteins at
      the apical ES (ectoplasmic specialization), a unique type of cell junction found
      between Sertoli cells and elongating/elongated spermatids. In the present review,
      we highlight recent findings that have made a significant impact on our
      understanding of this protein family in normal cell function and in disease, with
      the emphasis on the role of MTMs and MTMRs in spermatogenesis. We also describe a
      working model to explain how MTMR2 interacts with other proteins such as c-Src,
      dynamin 2, EPS8 (growth factor receptor pathway substrate 8) and ARP2/3 (actin
      related protein 2/3) at the apical ES and the apical TBC (tubulobulbar complex;
      tubular-like invaginations that function in the disassembly of the apical ES and
      in the recycling of its components) to regulate spermiation at late stage VIII of
      the seminiferous epithelial cycle.

PMID- 21175433
TI  - Potential use of rapamycin in HIV infection.
AB  - The strong need for the development of alternative anti-HIV agents is primarily
      due to the emergence of strain-resistant viruses, the need for sustained
      adherence to complex treatment regimens and the toxicity of currently used
      antiviral drugs. This review analyzes proof of concept studies indicating that
      the immunomodulatory drug rapamycin (RAPA) possesses anti-HIV properties both in
      vitro and in vivo that qualifies it as a potential new anti-HIV drug. It
      represents a literature review of published studies that evaluated the in vitro
      and in vivo activity of RAPA in HIV. RAPA represses HIV-1 replication in vitro
      through different mechanisms including, but not limited, to down regulation of
      CCR5. In addition RAPA synergistically enhances the anti-HIV activity of entry
      inhibitors such as vicriviroc, aplaviroc and enfuvirtide in vitro. RAPA also
      inhibits HIV-1 infection in human peripheral blood leucocytes-SCID reconstituted
      mice. In addition, a prospective nonrandomized trial of HIV patient series
      receiving RAPA monotherapy after liver transplantation indicated significantly
      better control of HIV and hepatitis C virus (HCV) replication among patients
      taking RAPA monotherapy. Taken together, the evidence presented in this review
      suggests that RAPA may be a useful drug that should be evaluated for the
      prevention and treatment of HIV-1 infection.

PMID- 21175434
TI  - Dextromethorphan, chlorphenamine and serotonin toxicity: case report and
      systematic literature review.
AB  - The aim of this review was to describe a patient with serotonin toxicity after an
      overdose of dextromethorphan and chlorphenamine and to perform a systematic
      literature review exploring whether dextromethorphan and chlorphenamine may be
      equally contributory in the development of serotonin toxicity in overdose. A
      Medline literature review was undertaken to identify cases of serotonin toxicity
      due to dextromethorphan and/or chlorphenamine. Case reports were included if they
      included information on the ingested dose or plasma concentrations of
      dextromethorphan and/or chlorphenamine, information about co-ingestions and
      detailed clinical information to evaluate for serotonin toxicity. Cases were
      reviewed by two toxicologists and serotonin toxicity, defined by the Hunter
      criteria, was diagnosed when appropriate. The literature was then reviewed to
      evaluate whether chlorphenamine may be a serotonergic agent. One hundred and
      fifty-five articles of dextromethorphan or chlorphenamine poisoning were
      identified. There were 23 case reports of dextromethorphan, of which 18 were
      excluded for lack of serotonin toxicity. No cases were identified in which
      serotonin toxicity could be solely attributed to chlorphenamine. This left six
      cases of dextrometorphane and/or chlorphenamine overdose, including our own, in
      which serotonin toxicity could be diagnosed based on the presented clinical
      information. In three of the six eligible cases dextromethorphan and
      chlorphenamine were the only overdosed drugs. There is substantial evidence from
      the literature that chlorphenamine is a similarly potent serotonin re-uptake
      inhibitor when compared with dextrometorphan. Chlorphenamine is a serotonergic
      medication and combinations of chlorphenamine and dextromethorphan may be
      dangerous in overdose due to an increased risk of serotonin toxicity.

PMID- 21175435
TI  - Simvastatin prevents inflammation-induced aortic stiffening and endothelial
      dysfunction.
AB  - AIMS: The aim of this study was to determine whether simvastatin would protect
      against inflammation-induced aortic stiffening and endothelial dysfunction.
      METHODS: Aortic pulse wave velocity (aPWV) and flow-mediated dilatation (FMD)
      were assessed three times, at baseline, after a 14 day administration of
      simvastatin or placebo and 8 h after Salmonella typhi vaccination in 50 healthy
      subjects. RESULTS: Following vaccination there was a significant increase in aPWV
      in the placebo group (5.80 +/- 0.87 vs. 6.21 +/- 0.97 m s-1, 95% CI 0.19, 0.62,
      P= 0.002) but not the simvastatin group (5.68 +/- 0.73 vs. 5.72 +/- 0.74 m s-1,
      95% CI -0.19, 0.27, P= 0.9; P= 0.016 for comparison). Whereas FMD response was
      reduced in the placebo group (6.77 +/- 4.10 vs. 5.27 +/- 2.88%, 95% CI -2.49, 
      0.52, P= 0.02) but not in the simvastatin group (7.07 +/- 4.37 vs. 7.17 +/-
      9.94%, 95% CI -1.1, 1.3. P= 0.9, P < 0.001 for comparison). There was no
      difference in the systemic inflammatory response between groups following
      vaccination. However, there was a significant reduction in serum apolipoprotein A
      I (Apo A-I) in the placebo, but not in the simvastatin, group. CONCLUSIONS:
      Simvastatin prevents vaccination-induced aortic stiffening and endothelial
      dysfunction. This protective mechanism may be due to preservation of the Apo A-I
      lipid fraction, rather than pleiotropic anti-inflammatory effects of statins.

PMID- 21175437
TI  - Comparison of the agonist-antagonist interaction model and the pool model for the
      effect of remoxipride on prolactin.
AB  - AIMS: The tolerance to the prolactin response following administration of
      antipsychotic drugs has been modelled as a depletion of a prolactin pool (pool
      model) and a model where the tolerance is explained by a feedback loop including
      the dopamine interaction of prolactin release (agonist-antagonist interaction
      model, (AAI model)). The AAI model was superior to the pool model when analyzing
      data from clinical trials of risperidone and paliperidone. Here we evaluated the
      two models using the remoxipride data, designed to challenge the short-term
      prolactin response, from which the original pool model was built. METHODS: The
      remoxipride data were collected from a study where eight healthy male subjects
      received two remoxipride infusions on five occasions. The intervals between the
      first and second dose on each occasion were 2, 8, 12, 24 and 48 h, respectively.
      The pool and AAI models were fitted using NONMEM. RESULTS: According to the
      objective function values the pool model with a circadian rhythm function fitted
      the data slightly better, while the AAI model was better in describing the
      circadian rhythm of prolactin. Visual predictive checks revealed that the models
      predicted the prolactin profiles equally well. CONCLUSIONS: According to the
      analysis performed here, a previous analysis of several clinical studies and
      literature reports on prolactin concentrations, it appears that the dopamine
      feedback mechanism included in the AAI model is better than the storage depletion
      mechanism in the pool model to estimate the bio-rhythm of prolactin time-course
      and the tolerance development across different populations, drugs, treatment
      schedules and time.

PMID- 21175436
TI  - Influence of hepatic impairment on pharmacokinetics of the human GLP-1 analogue,
      liraglutide.
AB  - AIMS: To compare the pharmacokinetics (PK) of a single-dose of liraglutide in
      subjects with hepatic impairment. METHODS: This parallel group, open label trial
      involved four groups of six subjects with healthy, mild, moderate and severe
      hepatic impairment, respectively. Each subject received 0.75 mg of liraglutide
      (s.c., thigh), and blood samples were taken over 72 h for PK assessment. Standard
      laboratory and safety data were collected. The primary endpoint was area under
      the plasma liraglutide concentration-time curve from time zero to infinity
      (AUC(0,infinity)). RESULTS: Exposure to liraglutide was not increased by hepatic
      impairment. On the contrary, mean AUC(0,infinity) was highest for healthy
      subjects and lowest for subjects with severe hepatic impairment (severe/healthy:
      0.56, with 90% CI 0.39, 0.81) and equivalence in this parameter across groups was
      not demonstrated. C(max) also tended to decrease with hepatic impairment
      (severe/healthy: 0.71, with 90% CI 0.52, 0.97), but t(max) was similar across
      groups (11.3-13.2 h). There were no serious adverse events, hypoglycaemic
      episodes or clinically significant changes in laboratory parameters and
      liraglutide was considered well tolerated. CONCLUSIONS: This study indicated no
      safety concerns regarding use of liraglutide in patients with hepatic impairment.
      Exposure to liraglutide was not increased by impaired liver function; rather, the
      results suggest a decreased exposure with increasing degree of hepatic
      impairment. However, data are not conclusive to suggest a dose increase of
      liraglutide. Thus, the results indicate that patients with type 2 diabetes
      mellitus and hepatic impairment can use standard treatment regimens of
      liraglutide. There is, however, currently limited clinical experience with
      liraglutide in patients with hepatic impairment.

PMID- 21175438
TI  - Lack of clinically relevant drug-drug interactions when dalcetrapib is co
      administered with ezetimibe.
AB  - AIMS: Dalcetrapib, which targets cholesteryl ester transfer protein activity, is
      in development for prevention of cardiovascular events. Because dalcetrapib will
      likely be prescribed with other lipid-modifying therapies such as ezetimibe, a
      study was performed to investigate potential pharmacokinetic interactions between
      dalcetrapib and ezetimibe. Lipids changes and tolerability were secondary
      endpoints. METHODS: Co-administration of dalcetrapib 900 mg (higher than the
      phase III dose) with ezetimibe was investigated in a three period, three
      treatment crossover study in healthy males: 7 days of dalcetrapib, 7 days of
      dalcetrapib plus ezetimibe, 7 days of ezetimibe alone. A full pharmacokinetic
      profile was performed on day 7 of each treatment. RESULTS: Co-administration of
      dalcetrapib with ezetimibe was associated with minimal changes in dalcetrapib
      exposure compared with dalcetrapib alone. Least squares mean ratio (LSMR) (90%
      confidence interval) was 93.6 (87.1, 100.7) for AUC(0,24 h) and 99.0 (85.2,
      115.0) for C(max) . Ezetimibe exposure was reduced with co-administration of
      ezetimibe with dalcetrapib compared with ezetimibe alone: LSMR 80.3 (74.6, 86.4)
      for AUC(0,24 h) and 88.9 (80.9, 99.9) for C(max) for total ezetimibe. High
      density lipoprotein cholesterol increases associated with co-administration of
      dalcetrapib with ezetimibe (+29.8%) were comparable with those with dalcetrapib
      alone (+25.6%), while the reduction in low-density lipoprotein cholesterol with
      co-administration (-35.9%) was greater than with ezetimibe alone (-20.9%).
      Dalcetrapib was generally well tolerated when administered alone and when co
      administered with ezetimibe. CONCLUSION: Co-administration of dalcetrapib with
      ezetimibe was not associated with clinically significant changes in
      pharmacokinetic parameters or tolerability and did not diminish the lipid effects
      of either drug.

PMID- 21175439
TI  - Effect of oseltamivir treatment on anticoagulation: a cross-over study in
      warfarinized patients.
AB  - AIM: To investigate whether oseltamivir enhances the anticoagulant effect of
      warfarin and to evaluate any pharmacokinetic (PK) interaction between the agents.
      METHODS: Twenty volunteers (mean age 62 years) receiving daily warfarin and with
      INR values of 2.0-3.5 during the previous 2 weeks were randomized to concomitant
      oseltamivir 75 mg twice daily for 4.5 days or warfarin alone in a two-way cross
      over design with a 4-8 day wash-out. Anticoagulant effects were assessed by
      calculating overall [AUEC(0,96 h)] and observed maximum effect (E(max) ) increase
      from baseline in INR, decrease from baseline in factor VIIa, and change in
      vitamin K1 concentrations. Plasma pharmacokinetics of (R)- and (S)-warfarin and
      oseltamivir were also assessed. RESULTS: For both treatments, changes in INR and
      factor VIIa during treatment were small; for net AUEC(0,96 h), least square mean
      values were -9.53 (oseltamivir + warfarin) and -1.69 h (warfarin alone) for INR
      (difference -7.84 h, 90% CI -18.86, 3.17 h), and 1.56 and 0.54 kIU l-1 h,
      respectively, for factor VIIa (difference, 1.01 kIU l-1 h; 90% CI -1.18, 3.21).
      Differences between the treatments in E(max) increase from baseline for INR,
      decrease from baseline for factor VIIa and change from baseline in vitamin K1
      concentration were not statistically significant. Oseltamivir did not alter
      warfarin pharmacokinetics. Oseltamivir was well tolerated in this study with no
      clinically significant adverse safety findings. CONCLUSION: Concomitant
      administration of oseltamivir for 4.5 days to volunteers on daily warfarin had
      little or no effect on warfarin pharmacokinetics and no effect on
      pharmacodynamics.

PMID- 21175440
TI  - The combined impact of CYP2C19 and CYP2B6 pharmacogenetics on cyclophosphamide
      bioactivation.
AB  - AIMS: The role of CYP pharmacogenetics in the bioactivation of cyclophosphamide
      is still controversial. Recent clinical studies have suggested a role for either
      CYP2C19 or CYP2B6. The aim of this study was to clarify the role of these
      pharmacogenes. METHODS: We used a combined in vitro-in vivo approach to determine
      the role of these pharmacogenes in the bioactivation of the prodrug to 4-hydroxy
      cyclophosphamide (4-OHCP). Cyclophosphamide metabolism was determined in a human
      liver biobank (n= 14) and in patients receiving the drug for treatment of lupus
      nephritis (n= 16) RESULTS: In livers of known CYP2C19 and CYP2B6 genotype and
      protein expression we observed that there was a combined role for both CYP2C19
      and CYP2B6 in the bioactivation of cyclophosphamide in vitro. The presence of at
      least one loss of function (LoF) allele at either CYP2C19 or CYP2B6 resulted in a
      significant decrease in both V(max) (P= 0.028) and CL(int) (P= 0.0017) compared
      with livers with no LoF alleles. This dual genotype relationship was also
      observed in a preliminary clinical study, with patients who had >=1 LoF allele at
      either CYP2C19 or CYP2B6 also displaying significantly (P= 0.0316) lower
      bioactivation of cyclophosphamide. The mean 4-OHCP : CP bioactivation ratio was
      0.0014 (95% CI 0.0007, 0.002) compared with 0.0071 (95% CI 0.0001, 0.014) in
      patients with no LoF alleles at either of these genes. CONCLUSIONS: The presence
      of >=1 LoF allele(s) at either CYP2B6 or CYP2C19 appeared to result in decreased
      bioactivation of cyclophosphamide both in vitro and in patients. Further clinical
      studies to confirm this relationship are warranted.

PMID- 21175441
TI  - In vitro and in vivo oxidative metabolism and glucuronidation of anastrozole.
AB  - AIMS: Little information is available regarding the metabolic routes of
      anastrozole and the specific enzymes involved. We characterized anastrozole
      oxidative and conjugation metabolism in vitro and in vivo. METHODS: A sensitive
      LC-MS/MS method was developed to measure anastrozole and its metabolites in vitro
      and in vivo. Anastrozole metabolism was characterized using human liver
      microsomes (HLMs), expressed cytochrome P450s (CYPs) and UDP
      glucuronosyltransferases (UGTs). RESULTS: Hydroxyanastrozole and anastrozole
      glucuronide were identified as the main oxidative and conjugated metabolites of
      anastrozole in vitro, respectively. Formation of hydroxyanastrozole from
      anastrozole was markedly inhibited by CYP3A selective chemical inhibitors (by
      >90%) and significantly correlated with CYP3A activity in a panel of HLMs (r=
      0.96, P= 0.0005) and mainly catalyzed by expressed CYP3A4 and CYP3A5. The K(m)
      values obtained from HLMs were also close to those from CYP3A4 and CYP3A5.
      Formation of anastrozole glucuronide in a bank of HLMs was correlated strongly
      with imipramine N-glucuronide, a marker of UGT1A4 (r= 0.72, P < 0.0001), while
      expressed UGT1A4 catalyzed its formation at the highest rate. Hydroxyanastrozole
      (mainly as a glucuronide) and anastrozole were quantified in plasma of breast
      cancer patients taking anastrozole (1 mg day-1); anastrozole glucuronide was less
      apparent. CONCLUSION: Anastrozole is oxidized to hydroxyanastrozole mainly by
      CYP3A4 (and to some extent by CYP3A5 and CYP2C8). Once formed, this metabolite
      undergoes glucuronidation. Variable activity of CYP3A4 (and probably UGT1A4),
      possibly due to genetic polymorphisms and drug interactions, may alter
      anastrozole disposition and its effects in vivo.

PMID- 21175442
TI  - Repaglinide-gemfibrozil drug interaction: inhibition of repaglinide
      glucuronidation as a potential additional contributing mechanism.
AB  - AIM: To further explore the mechanism underlying the interaction between
      repaglinide and gemfibrozil, alone or in combination with itraconazole. METHODS:
      Repaglinide metabolism was assessed in vitro (human liver subcellular fractions,
      fresh human hepatocytes, and recombinant enzymes) and the resulting incubates
      were analyzed, by liquid chromatography-mass spectrometry (LC-MS) and
      radioactivity counting, to identify and quantify the different metabolites
      therein. Chemical inhibitors, in addition to a trapping agent, were also employed
      to elucidate the importance of each metabolic pathway. Finally, a panel of human
      liver microsomes (genotyped for UGT1A1*28 allele status) was used to determine
      the importance of UGT1A1 in the direct glucuronidation of repaglinide. RESULTS:
      The results of the present study demonstrate that repaglinide can undergo direct
      glucuronidation, a pathway that can possibly contribute to the interaction with
      gemfibrozil. For example, [3H]-repaglinide formed glucuronide and oxidative
      metabolites (M2 and M4) when incubated with primary human hepatocytes.
      Gemfibrozil effectively inhibited (~78%) both glucuronide and M4 formation, but
      had a minor effect on M2 formation. Concomitantly, the overall turnover of
      repaglinide was also inhibited (~80%), and was completely abolished when
      gemfibrozil was co-incubated with itraconazole. These observations are in
      qualitative agreement with the in vivo findings. UGT1A1 plays a significant role
      in the glucuronidation of repaglinide. In addition, gemfibrozil and its
      glucuronide inhibit repaglinide glucuronidation and the inhibition by gemfibrozil
      glucuronide is time-dependent. CONCLUSIONS: Inhibition of UGT enzymes, especially
      UGT1A1, by gemfibrozil and its glucuronide is an additional mechanism to consider
      when rationalizing the interaction between repaglinide and gemfibrozil.

PMID- 21175443
TI  - Evaluation of a QT nomogram for risk assessment after antidepressant overdose.
AB  - AIMS: A QT-heart rate nomogram has recently been proposed as a means of
      identifying patients at risk of torsades de pointes after antidepressant
      overdose, based on published cases of drug-induced torsades de pointes. The
      present study sought to examine the performance of the nomogram in patients who
      ingest an antidepressant overdose but do not develop arrhythmia. METHODS: A
      retrospective case control study of patients presenting to hospital after
      overdose of citalopram, mirtazapine and venlafaxine was carried out. The primary
      outcome variable was QT higher than the nomogram, and was compared with
      occurrence of QT(c) (QT corrected by Bazett's formula) greater than >=440 ms and
      QT(c) >=500 ms, with comparison between drugs. Data are expressed as proportions
      in each group with 95% confidence intervals. RESULTS: There were 858
      electrocardiograms from 541 patients. QT was higher than the nomogram in 2.4%
      (1.4, 4.1%), whereas QT(c) was >=440 ms in 23.1% (95% CI 19.8, 26.8%), and QT(c)
      was >=500 ms in 1.1% (0.5, 2.5%). Citalopram overdose was more likely to be
      associated with QT higher than the nomogram compared with the other agents
      (difference 7.0%, 95% CI 2.9, 11.9%, P = 0.001) and more likely to be associated
      with QT(c) >=440 ms (difference = 11.0%, 95% CI 2.6, 19.0%, P = 0.013).
      CONCLUSIONS: The QT nomogram was associated with a lower false positive rate than
      widely accepted QT(c) criteria, and allowed detection of different effects of
      individual drugs. The nomogram offers potential advantages over QT(c) criteria
      and merits further investigation in a clinical setting.

PMID- 21175444
TI  - Cortisol response to individualised graded insulin infusions: a reproducible
      biomarker for CNS compounds inhibiting HPA activation.
AB  - AIM: To determine the potential of cortisol secretion, in response to a
      physiological stressor, as a biomarker for centrally active compounds targeting
      the hypothalamic-pituitary-adrenocortical (HPA) axis. METHODS: Cortisol response
      to hypoglycaemia was measured in 26 healthy males in two stages: firstly to
      derive an algorithm for individualized, graded insulin infusion rates to achieve
      defined hypoglycaemic targets over 3 h and secondly to determine the inter- and
      intra-subject variability of cortisol response to hypoglycaemia over two
      identical periods by measuring the maximum (t(max) ), time to maximum (C(max) )
      response and cortisol area under the response curve (AUC). RESULTS: Hypoglycaemia
      induced a consistent cortisol response starting at approximately 1 h,
      corresponding to blood glucose concentrations of approximately 3.3 mmol l-1, and
      peaking approximately 3 h after the start of infusion. The inter- and intra
      subject coefficients of variation (CVs) of cortisol response were approximately
      19 and 19% (AUC), 15 and 19 % (C(max) ) and 10 and 14% (t(max) ), respectively.
      The intra-subject CVs for the ratio of maximum cortisol response to baseline
      concentration and rate of initial cortisol response between study days were more
      variable (32.8% and 59.0%, respectively). The blood glucose-cortisol response
      model derived from the study was predictive of the individual observed cortisol
      responses, and estimated a blood glucose EC(50) associated with onset of the
      cortisol response of 3.3 mmol l-1. CONCLUSIONS: Gradual hypoglycaemia is an
      effective, reproducible and well-tolerated method of stimulating a cortisol
      response and may therefore be useful in assessing the neuroendocrine response to
      HPA axis inhibitors, such as corticotropin-releasing hormone-1 (CRH-1)
      antagonists.

PMID- 21175445
TI  - (R)- and (S)-methadone and buprenorphine concentration ratios in maternal and
      umbilical cord plasma following chronic maintenance dosing in pregnancy.
AB  - AIMS: The aim of this study was to compare the transfer of buprenorphine and
      methadone between maternal and cord blood in women under chronic dosing
      conditions and to determine if differences exist in the transfer of the two
      methadone enantiomers. METHODS: Maternal and cord blood samples were collected at
      delivery from women maintained on methadone (35, 25-140 mg day-1) (median; range)
      or buprenorphine (6.00, 2-20 mg day-1) during pregnancy. Plasma concentration
      ratios are presented as an indicator of foetal exposure relative to the mother.
      RESULTS: Methadone was quantified in all samples, with cord : maternal plasma
      methadone concentration ratios (n= 15 mother-infant pairs) being significantly
      higher (P < 0.0001; mean difference (MD) 0.07; 95% confidence interval (CI)
      0.048, 0.092) for the active (R)-methadone enantiomer (0.41; 0.19, 0.56) (median;
      range) compared with (S)-methadone (0.36; 0.15, 0.53). (R)- : (S)-methadone
      concentration ratios were also significantly higher (P < 0.0001; MD 0.24 95% CI
      0.300, 0.180) for cord (1.40; 0.95, 1.67) compared with maternal plasma (1.16;
      0.81, 1.38). Half the infant buprenorphine samples were below the assay lower
      limit of quantification (LLOQ) (0.125 ng ml-1). The latter was four-fold lower
      than the LLOQ for methadone (0.50 ng ml-1). The cord : maternal plasma
      buprenorphine concentration ratio (n= 9 mother-infant pairs) was 0.35; 0.14, 0.47
      and for norbuprenorphine 0.49; 0.24, 0.91. CONCLUSIONS: The transfer of the
      individual methadone enantiomers to the foetal circulation is stereoselective.
      Infants born to buprenorphine maintained women are not exposed to a greater
      proportion of the maternal dose compared with methadone and may be exposed to
      relatively less of the maternal dose compared with infants born to women
      maintained on methadone during pregnancy.

PMID- 21175446
TI  - The NK1 receptor antagonist aprepitant does not alter the pharmacokinetics of
      high-dose melphalan chemotherapy in patients with multiple myeloma.
AB  - AIMS: The objective of this investigation was to assess the effect of aprepitant
      on the pharmacokinetics of high-dose melphalan used as conditioning therapy
      before blood stem cell transplantation in multiple myeloma. METHODS: Aprepitant
      (125 mg) or placebo was administered 1 h before melphalan therapy (1 h infusion
      of 100 mg m-2). Eleven plasma samples were obtained over 8 h and melphalan was
      quantified using an LC/MS/MS method. Standard pharmacokinetic parameters were
      calculated and nonparametric testing was applied to assess the differences
      between aprepitant and placebo treatment. RESULTS: Twenty patients received
      placebo and 10 patients aprepitant treatment. There were no differences observed
      for C(max) at the end of melphalan infusion (placebo 3431 +/- 608 ng ml-1 vs.
      aprepitant 3269 +/- 660 ng ml-1). In addition, AUC and terminal elimination half
      life were not changed by aprepitant. Total clearance of melphalan was 304 +/- 58
      ml min-1 m-2 (placebo) which was not influenced by aprepitant (288 +/- 78 ml min
      1 m-2). CONCLUSIONS: The administration of the NK1 receptor antagonist aprepitant
      1 h before a high-dose chemotherapy does not influence the exposure and the
      elimination of melphalan. Therefore, oral administration of 125 mg aprepitant 1 h
      before melphalan infusion does not alter the disposition of intravenously
      administered melphalan.

PMID- 21175447
TI  - Erlotinib and pantoprazole: a relevant interaction or not?
AB  - AIMS: There is increasing evidence that erlotinib exposure correlates well with
      treatment outcome. In this report we present a case of therapeutic drug
      monitoring of erlotinib in a patient with a gastric ulcer, treated with the
      proton pump inhibitor pantoprazole. This agent may cause an unwanted, but not
      always unavoidable, interaction since absorption of erlotinib is pH dependent.
      METHODS: Erlotinib trough concentrations were monitored in a patient during
      treatment with orally and intravenously administered pantoprazole. RESULTS:
      Erlotinib trough concentrations were diminished during high dose intravenously
      administered pantoprazole, but returned to normal when the dose was reduced and
      pantoprazole was administered orally. CONCLUSIONS: More studies are needed to
      assess the dose dependency of the interaction between pantoprazole and erlotinib.
      Furthermore, we advise to monitor closely erlotinib plasma concentrations and
      adjust the erlotinib dose accordingly when a clinically relevant interaction is
      suspected and no proper dosing guidelines are available.

PMID- 21175448
TI  - A response to: 'A manifesto for clinical pharmacology from principles to
      practice' by Jeff Aronson.

PMID- 21175449
TI  - Temporomandibular dislocation due to aripiprazole induced dystonia.

PMID- 21175450
TI  - Case discussion of an immediate serious reaction to hexavalent vaccine mistaken
      for anaphylaxis.

PMID- 21175453
TI  - Pertussis vaccine encephalopathy: 'Oh! Let us never, never doubt '....

PMID- 21175454
TI  - Clinical assessment of dynamic hand control in pediatrics.

PMID- 21175456
TI  - Variation at local government level in the support for families of severely
      disabled children and the factors that affect it.
AB  - AIM: The aim of this study was to examine geographical variability in the support
      for families caring for children with severe disabilities as well as the
      relationships between this variability and local government social and
      educational performance indicators. METHOD: Data were collected from a cross
      sectional, self-completed postal survey of the families of 5862 children and
      young people (aged 0-24 y, mean 10 y 7 mo; 68% male) with severe disabilities
      resulting in a variety of impairments (21% with autism spectrum disorders, 16%
      with learning disabilities,* 13% with emotional and behavioural difficulties, and
      13% with cerebral palsy [CP]). Data on the severity of intrinsic impairment were
      assessed using the Health Utilities Index, and the need for support was assessed
      from the results of a novel parent-completed questionnaire, the European Child
      Environment Questionnaire (ECEQ). These responses were related to data published
      by local authorities on educational and social policy. RESULTS: Higher levels of
      unmet need and lack of support, as reported by parents of children and young
      people with severe disabilities, are associated with greater impairment but not
      with socioeconomic deprivation. After controlling for impairment and diagnosis,
      variation at local government level is of the order of 1 to 1.5 ECEQ standard
      deviation scores. The best- and the worst-performing local authorities--in terms
      of the averages of the 'support' scores reported by their surveyed residents-
      cluster in urban areas. For children with CP, a positive correlation was found
      between the reported unmet educational support requirements in each local
      authority area and rates of mainstream school placement for children with special
      educational needs. This indicates that the placement of children with
      disabilities into mainstream schools is associated with reported unmet need
      (r=0.60; p=0.01). In the case of children with autism spectrum diagnoses, the
      provision of additional basic educational support in mainstream primary education
      was associated with lower average local authority scores for unmet need,
      suggesting that this support was appreciated by residents (r=-0.75; p=0.005).
      INTERPRETATION: Parent-reported unmet need in the care of children with
      disabilities shows significant geographical variation after adjustments for
      severity, type of impairment, and socioeconomic deprivation. Associations between
      some aspects of reported unmet need and local authority performance indicators
      suggest that support for families of children with severe disabilities may be
      improved by policy changes at local government level.

PMID- 21175457
TI  - Grappling with the grey evidence.

PMID- 21175458
TI  - Intractable epilepsy in tuberous sclerosis: is the tuber removal not enough?

PMID- 21175459
TI  - Progressive calcified tuber in a young male with tuberous sclerosis complex.
AB  - Tubers are the most common brain lesions in tuberous sclerosis complex (TSC), and
      typically remain stable in size and appearance. We present the case of a young
      male with global developmental impairment and autistic features as well as
      multiple and mixed daily seizures. The patient had a prominent right frontal
      cortical tuber characterized by a calcified component, which changed on
      consecutive magnetic resonance imaging between the age of 4 and 11 years, at
      which time the patient underwent a lesionectomy. A poor long-term outcome is
      reported since the patient presents an intractable mixed seizure disorder status
      post-epilepsy surgery and no significant neuropsychological improvements.
      Histopathology findings show typical characteristics of tubers in TSC as well as
      numerous calcifications within the resected nodular lesion. This case supports
      the notion that tubers with calcified components are not necessarily static
      lesions and can change with time. Investigation of the relationship between the
      presence of calcification in tubers and epileptogenecity in a large group of
      patients would provide insights into the pathogenesis of the seizures and
      cognitive impairment and hopefully, eventually provide better treatment options
      for patients with TSC.

PMID- 21175461
TI  - Cognitive and perceptual visual impairment: recognition and intervention.

PMID- 21175462
TI  - Gastrostomy feeding in cerebral palsy: enough and no more.

PMID- 21175463
TI  - Some reflections on mirror movements.

PMID- 21175464
TI  - Persisting cognitive deficits in survivors of very low birthweight and their
      implications for adult functioning.

PMID- 21175465
TI  - Periventricular calcification added to the phenotypic repertoire of Alexander
      disease.

PMID- 21175466
TI  - Utility of language comprehension tests for unintelligible or non-speaking
      children with cerebral palsy: a systematic review.
AB  - AIM: to identify the use and utility of language comprehension tests for
      unintelligible or non-speaking children with severe cerebral palsy (CP). METHOD:
      severe CP was defined as severe dysarthria (unintelligible speech) or anarthria
      (absence of speech) combined with severe limited mobility, corresponding to Gross
      Motor Function Classification System levels IV to V. An electronic search in the
      databases of PubMed, PsychInfo, Embase, and CINAHL was made of studies published
      between January 1965 and December 2008. Indexing terms and free-text terms for
      'cerebral palsy', 'language', and 'instrumentation' were used. Studies were
      included when (1) the focus was to investigate comprehension of spoken language
      of children (0-18 y) with severe CP, and (2) language tests were described.
      RESULTS: twelve standardized tests and five experimental instruments were
      identified. All standardized tests were developed for children without limited
      mobility. Only the Peabody Picture Vocabulary Test - Revised was frequently used
      and feasible for older children with severe CP (> 9y). The other tests were used
      occasionally. To establish utility, adaptations of standardized test procedures
      were necessary. INTERPRETATION: language comprehension tests for children with
      severe CP are scarce. A language comprehension test specifically designed for
      these children is warranted. Cite this as: Dev Med Child Neurol 52: e267-e277.

PMID- 21175467
TI  - Cognitive profile in young adults born preterm at very low birthweight.
AB  - AIM: the aim of this study was to assess cognitive function at the age of 19
      years in individuals of very low birthweight (VLBW; <= 1500g) and in term-born
      comparison individuals. METHOD: in this hospital-based follow-up study, 55 VLBW
      participants (30 males, 25 females; mean birthweight 1217g, SD 233g; mean
      gestational age 29.1wks, SD 2.5wks) and 81 comparison individuals (42 males, 39
      females; mean birthweight 3707g, SD 433g; mean gestational age 39.7wks, SD
      1.2wks) were examined with a standardized IQ test (Wechsler Adult Intelligence
      Scale III) to assess general cognitive ability. RESULTS: over half (53%) of the
      VLBW participants achieved a low IQ score (defined as >1SD below the mean in the
      comparison group; odds ratio 6.4 vs comparison individuals; 95% confidence
      interval 2.8-14.4; p<0.001). None of the VLBW group, compared with 22% of the
      comparison individuals, achieved a high IQ score (>1SD above the comparison
      mean). VLBW participants scored lower than comparison individuals on full,
      verbal, and performance IQ, as well as on all four indices (p <=0.001). The
      subtest profile indicated problems on all subtests, but especially on those
      related to arithmetic and visual-perceptual tasks. INTERPRETATIONS: few studies
      have undertaken a comprehensive assessment of general cognitive outcome (IQ)
      among young adults of VLBW. Our results indicate that VLBW seems to have a global
      and lasting impact on cognitive ability. Full-scale IQ assessment may reveal
      important learning problems in young adults of VLBW, and should be performed to
      inform appropriate assistance to enhance academic achievement and the chances of
      permanent employment as adults.

PMID- 21175468
TI  - Early developmental assessment of children with major non-cardiac congenital
      anomalies predicts development at the age of 5 years.
AB  - AIM: the aim of this study was to evaluate cognitive and motor development in
      children with major congenital anomalies and the predictability of development at
      age 5 years. METHOD: a prospective, longitudinal follow-up study was undertaken.
      The Dutch version of the Bayley Scales of Infant Development - Mental
      Developmental Index (MDI) and Psychomotor Developmental Index (PDI) - were
      administered at the ages of 6, 12, and 24 months. The Revised Amsterdam
      Children's Intelligence Test - IQ and the Movement Assessment Battery for
      Children - Total impairment score (TIS) were used at age 5 years. A total of 117
      children participated in the study. After excluding 12 children who had a major
      chromosomal or syndromal abnormality, the analysis was limited to 105 children
      (50 females, 55 males). Seven groups of congenital anomalies were distinguished:
      (1) small intestinal anomalies; (2) abdominal wall defects, comprising
      gastroschisis and omphalocele; (3) oesophageal atresia; (4) congenital
      diaphragmatic hernia; (5) Hirschsprung disease; (6) anorectal malformations; and
      (7) miscellaneous diagnoses. Logistic regression analyses served to determine the
      ability of MDI and PDI to predict IQ and TIS at age 5 years. RESULTS: at age
      five, 83.7% of 104 children had an IQ of 85 or above and 16.3% an IQ of less than
      85. TIS was normal in 71.3% of 87 children, while 17.2% demonstrated a borderline
      score and 11.5% a definite motor problem. MDI and PDI scores showed equal
      sensitivity to predict IQ (p=0.004 at 6 and 12mo, p=0.001 at 24mo) and TIS
      (p<0.001 at 6 and 12mo, p=0.002 at 24mo). MDI and PDI were positively correlated
      with IQ and TIS; TIS was positively correlated with IQ. INTERPRETATION: IQ scores
      at 5 years of age corresponded to Dutch population scores, but TIS scores
      differed significantly. Early development of children with major congenital
      anomalies is predictive of development at 5 years, which can guide individualized
      follow-up for this vulnerable group of children.

PMID- 21175470
TI  - Absence of acute adverse in-vitro effects on AS-1 RBCs and whole blood-derived
      platelets following prolonged exposure to 13.56 MHz radio energy.
AB  - BACKGROUND: There is growing interest in radio frequency identification (RFID)
      technology application for tracking blood products to achieve higher productivity
      and safety in the transfusion medicine supply chain. We have conducted a limited
      study to assess the temperature and biological effects of 13.56 MHz RF radiation
      on RBCs and whole blood-derived platelets (WBDP) under extreme exposure
      conditions. STUDY DESIGN AND METHODS: Using an FDA-approved protocol, test units
      of both RBC and WBDP were subjected to approximately 100 watts of RF energy for
      an extended duration (23-25 h) to assess worst-case effects. Three replications
      of the test were performed. RESULTS: Hemolysis after 23-25 hours of RF energy
      exposure was 0.09% and 0.05%, respectively, for TEST and CONTROL RBC units and
      well within the <=1% limit in the FDA-approved acceptance criteria. For WBDP
      units, the mean pH of TEST and CONTROL units were 7.27 and 7.19, respectively,
      following 23-25 hours of RF energy exposure, and well above the >=6.2 acceptance
      limit. Further, there was no detectable acceleration in cellular degradation of
      RBC and WBDP products. While there was minimal temperature rise, the relative
      temperature increase between TEST and CONTROL units never exceeded the 1.5
      degrees C acceptance criterion. CONCLUSIONS: 13.56 MHz-based RFID technology is
      unlikely to have any significant temperature or biological effects on RBC and
      WBDP units under the normal operating conditions (a maximum of 4 watts RF power
      exposure for about 20 nonconsecutive minutes for RFID tracking during the life of
      the blood product).

PMID- 21175471
TI  - Business continuity: mitigating and responding to ensure continuous customer
      support.

PMID- 21175472
TI  - Evaluating the impact of the blood drive "person-in-charge" on blood drive
      effectiveness.

PMID- 21175473
TI  - Organization and management of an accredited specialist in blood bank (SBB)
      technology program.
AB  - BACKGROUND: Specialists in blood bank (SBBs) technology play important roles in
      blood banks, transfusion services, regulatory agencies, educational institutions,
      and other facilities where expertise in blood banking, transfusion medicine,
      cellular therapy, and tissue transplantation is required. STUDY DESIGN: Review of
      pathways that qualify applicants for a national examination administered by the
      American Society of Clinical Pathology (ASCP) to become a certified specialist
      and outcomes of accredited programs. Description of a face-to-face, accredited
      program including review of management topics included in curriculum. RESULTS:
      The first examination was administered in 1954. As of December 2009, the total
      number of certified SBBs was 5124. There are currently 16 accredited SBB programs
      in the United States. The programs vary in mode of delivery, length of program,
      number of students accepted, and organization of program officials and faculty,
      but all must follow specific standards and guidelines in order to be accredited.
      CONCLUSION: Students who successfully complete SBB programs have a higher passing
      rate than those who attempt the certification examination and have not
      participated in a program. Students can choose among a variety of programs that
      differ widely in the way they are managed. The role of management in an SBB
      program ranges from attracting and retaining individuals and maintaining an
      accredited program to finally graduating individuals who not only pass the
      certification examination but who also confidently contribute to the field.

PMID- 21175474
TI  - Using an integrated automated system to optimize retention and increase frequency
      of blood donations.
AB  - BACKGROUND: This study examines the impact of an integrated, automated phone
      system to reinforce retention and increase frequency of donations among blood
      donors. STUDY DESIGN AND METHODS: Cultivated by incorporating data results over
      the past 7 years, the system uses computerized phone messaging to contact blood
      donors with individualized, multilevel notifications. Donors are contacted at
      planned intervals to acknowledge and recognize their donations, informed where
      their blood was sent, asked to participate in a survey, and reminded when they
      are eligible to donate again. RESULTS: The report statistically evaluates the
      impact of the various components of the system on donor retention and blood
      donations and quantifies the fiscal advantages to blood centers. CONCLUSIONS: By
      using information and support systems provided by the automated services and then
      incorporating the phlebotomists and recruiters to reinforce donor retention, both
      retention and donations will increase.

PMID- 21175475
TI  - Design of a donor-driven data collection strategy for operational improvement of
      blood donation process.
AB  - BACKGROUND: Prior studies have noted that donor retention may be negatively
      impacted by the total time it takes to complete the blood donation process. STUDY
      DESIGN AND METHODS: To gain a comprehensive understanding of the blood donation
      process and examine opportunities for operational improvements, an educational
      partnership established between a blood bank and a university designed and
      implemented a donor-driven data collection strategy. RESULTS: A large amount of
      real-time, comprehensive, donor-reported data was collected as donors navigated
      the process, which has enabled a thorough analysis of the process and its
      potential improvements. CONCLUSION: In this paper, we describe the design and
      implementation efforts, examine the challenges in operationalizing a donor-driven
      data collection approach, and present insights and recommendations for its
      application in similar settings.

PMID- 21175477
TI  - Angiogenesis in superficial esophageal squamous cell carcinoma: magnifying
      endoscopic observation and molecular analysis.
AB  - Observations of esophageal squamous cell carcinoma using magnifying endoscopy
      have now been carried out extensively and, as a result, it has become clear that
      the morphology of the microvessels evident at the tumor surface reflects the
      depth of tumor invasion. In M1 and M2 cancer, the surface microvasculature
      reveals dilation and elongation of the intrapapillary capillary loops (IPCL).
      However, at this stage, some immature capillaries resembling IPCL also arise
      inside the tumor and, therefore, the view of the microvasculature should be
      described as one showing 'intermixing of modified IPCL and IPCL-like immature
      capillaries (IPCL-like abnormal capillary)'. As cancer invades into the
      muscularis mucosa (M3 or deeper), an obviously dilated and irregularly branched
      tumor-specific vasculature, more accurately described as 'neovasculature', can be
      observed. From our magnifying endoscopy observations and studies of the molecular
      profile of early esophageal cancer, we conclude that two major angiogenic steps
      exist in precancerous and M3 lesions in the early phase of cancer progression. In
      addition, it is now possible to study cell morphology using an endocytoscope with
      a much higher magnification (*400-*1000) than magnifying endoscopes currently on
      the market. The histology revealed in this way may reduce the need for
      conventional biopsy histology in the future.

PMID- 21175478
TI  - Diagnosis and clinical course of ulcerative gastroduodenal lesion associated with
      ulcerative colitis: possible relationship with pouchitis.
AB  - BACKGROUND AND AIM:   Ulcerative colitis (UC) is not only characterized by
      pathological lesions localized to colonic mucosa, but also to various
      complications involving other organs, including postoperative pouchitis. Among
      these complications, diffuse gastroduodenitis with lesions resembling colonic
      lesions has been reported, albeit rarely.The aim of the present study was to
      attempt to characterize the lesions of the upper gastrointestinal tract occurring
      as a complication of UC, and to assess the frequency and clinical course of these
      lesions. METHODS:   A total of 322 UC patients who had undergone upper
      gastrointestinal endoscopy were retrospectively analyzed. We assessed the
      frequency of endoscopic findings, including diffuse gastroduodenal lesions
      resembling colonic lesions. Ulcerative gastroduodenal lesion (UGDL) associated
      with UC was diagnosed if lesions satisfied the following criteria: (i)
      improvement of the lesions with treatment of UC; and/or (ii) resemblance to UC in
      pathological findings. RESULTS:   UGDL satisfying the aforementioned criteria was
      found in 15 (4.7%) of 322 patients. All the 15 patients had UGDL accompanied by
      pancolitis or after proctocolectomy. Frequency in 146 patients with pancolitis
      was 6.2% (nine patients) and that in 81 patients who had undergone
      proctocolectomy was 7.4% (six patients). Four patients with diffuse ulcerative
      upper-gastrointestinal mucosal inflammation (DUMI) had pouchitis. In all patients
      except one, the lesions resolved easily with medical treatment. CONCLUSIONS:   In
      more than half of the post-proctocolectomy patients, UGDL was related to the
      occurrence of pouchitis. The existence of characteristic UGDL must be taken into
      account in the diagnosis and treatment of UC, and UGDL is possibly related to the
      occurrence of pouchitis.

PMID- 21175479
TI  - Clinical characteristics and treatment for patients presenting with bleeding
      duodenal varices.
AB  - BACKGROUND AND AIM: Bleeding from ectopic varices, including duodenal varices, is
      uncommon, but it can be difficult to manage. The clinical data of patients
      diagnosed and treated for duodenal varices were reviewed to investigate the
      strategy for treatment. METHODS: The present study reviewed the clinical data of
      10 patients with duodenal varices (mean age, 58.2 +/- 15.6 years) at our
      associated institutes during the period between January 1996 and December 2008.
      RESULTS: Nine patients had duodenal varices located in the second portion,
      whereas in one case they were located in the duodenal bulbus. The underlying
      diseases included liver cirrhosis in eight patients, and extrahepatic portal vein
      obstruction in two patients. The lesions were identified with bleeding from
      varices in eight of 10 patients. Initial hemostasis was achieved in all eight
      patients. However, among four patients treated endoscopically only, two patients
      died from rebleeding from varices and two died from hepatic failure resulting
      from variceal bleeding. Additional interventional radiology (IVR) was used in
      three patients and additional surgery was carried out in one case. One patient
      who was treated with balloon-occluded retrograde transvenous obliteration rebled
      during IVR and died from bleeding. Two patients who underwent double balloon
      occluded embolotherapy and one case who had surgery achieved good clinical
      outcomes. CONCLUSIONS: Although endoscopic treatment is useful for initial
      hemostasis of hemorrhagic duodenal varices, the patients who underwent additional
      IVR after endoscopic treatment achieved good outcomes.

PMID- 21175480
TI  - Stricture after endoscopic submucosal dissection for early gastric cancers and
      adenomas.
AB  - BACKGROUND AND AIM:  Stricture is a complication that may occur after endoscopic
      submucosal dissection (ESD) of gastric neoplasms. The goal of the present study
      was to investigate the incidence, risk factors and management of gastric
      stricture after ESD. METHODS: The medical records of 308 patients who underwent
      ESD for gastric neoplasms were reviewed. Stricture is defined as having symptoms
      caused by an obstruction through which a 1-cm diameter endoscopic fiber cannot be
      passed. RESULTS: Stricture was identified in six of 308 patients (1.9%). Three of
      the six lesions were located in the prepylorus, two cases in the antrum and one
      in the cardia. The mean longitudinal distance and the mean area of the resected
      specimens in the six cases with stricture (7.8 +/- 2.0 cm, 34.0 +/- 15.8cm(2) ,
      respectively) was significantly larger than in those without stricture (4.5 +/-
      1.4cm, 12.7 +/- 8.3cm(2) , respectively, P<0.01). The ratio of the resected
      circumference/whole circumference was 83.3+/-7.5% in those with stricture in
      comparison to 25.4 +/- 16.3% in those without stricture (P<0.01). All six
      patients underwent endoscopic balloon dilations, and obtained relief from
      stricture. However, one patient experienced a gastric perforation and recovered
      following conservative therapy. CONCLUSION:  Sub-circumferential resection over
      75% of the circumference by ESD in the prepylorus, antrum and cardia is a risk
      factor for the occurrence of stricture. Early intervention might be considered
      for this high-risk group to avoid a perforation during balloon dilation.

PMID- 21175481
TI  - Tolerability and usefulness of mercaptopurine in azathioprine-intolerant Japanese
      patients with ulcerative colitis.
AB  - BACKGROUND AND AIM: Azathioprine (AZA) and mercaptopurine (6-MP) are established
      as effective therapeutic drugs for the induction and maintenance of remission in
      patients with ulcerative colitis (UC). However, AZA is often intolerable due to
      adverse effects. Evidence regarding the approach of switching from AZA to 6-MP in
      patients of Asian ethnicity is lacking. We assessed the tolerability and
      usefulness of 6-MP in Japanese UC patients who had shown intolerance to AZA.
      METHODS: One-hundred and ten UC patients who had been treated with AZA and/or 6
      MP from January 1985 to October 2008 were examined retrospectively. RESULTS:
      Among 110 patients, 107 were treated first with AZA; only three were treated
      first with 6-MP. Thirty-five (33%) of the 107 patients were intolerant of AZA,
      with adverse effects including myelosuppression (8/35, 23%), hepatotoxicity
      (8/35, 23%), and abdominal symptoms (6/35, 17%). Among 35 AZA-intolerant
      patients, 23 were switched to 6-MP treatment. The cumulative probability of
      colectomy was significantly higher in patients not treated with 6-MP than in
      patients treated with 6-MP (log-rank test, P =0.0002). Among the 26 patients (23
      AZA-intolerant and three AZA-untreated) treated with 6-MP, 22 (85%) could
      tolerate the therapy. Adverse effects due to 6-MP were abdominal symptoms (2/4),
      myelosuppression (1/4), and rash (1/4). The median initial dose of 6-MP was 20
      mg/day, and the median final dose was 30 mg/day. CONCLUSIONS:  6-MP was tolerated
      in 83% of AZA-intolerant patients, and it was effective for maintenance therapy
      of UC patients. 6-MP treatment should be considered in AZA-intolerant patients.

PMID- 21175482
TI  - Does a patent accessory pancreatic duct prevent acute pancreatitis?
AB  - BACKGROUND AND AIM: The role of the accessory pancreatic duct (APD) in pancreatic
      pathophysiology has been unclear. We previously examined the patency of the APD
      in 291 control cases who had a normal pancreatogram in the head of the pancreas
      by dye-injection endoscopic retrograde pancreatography (ERP). APD patency was 43%
      and was closely related with the shape of the terminal portion of the APD. The
      present study aimed to clarify the clinical implications of a patent APD.
      METHODS: Based on the underlying data, the patency rate of the APD was estimated
      from the terminal shape of the APD on ERP in 167 patients with acute
      pancreatitis. RESULTS: In patients with acute pancreatitis, stick-type APD,
      spindle-type APD, and cudgel-type APD, which showed a high patency, were rare,
      and branch-type APD and halfway-type or no APD, which showed quite low patency,
      were frequent in acute pancreatitis patients. Accordingly, the estimated patency
      of the APD in acute pancreatitis patients was only 21%. There was no significant
      relationship between the estimated APD patency and etiology or severity of acute
      pancreatitis. CONCLUSIONS: The terminal shapes of the APD with low patency were
      frequent in acute pancreatitis patients, and estimated APD patency was only 21%
      in acute pancreatitis. A patent APD may function as a second drainage system to
      reduce the pressure in the main pancreatic duct and prevent acute pancreatitis.

PMID- 21175483
TI  - Learning curve for endoscopic submucosal dissection of large colorectal tumors.
AB  - BACKGROUND AND AIM: No studies have previously described the learning curve for
      colonic endoscopic submucosal dissection (ESD). The aim of the present study was
      to describe the learning curve for ESD of large colorectal tumors based on a
      single colonoscopist's experience. METHODS: ESD was carried out for 120
      colorectal tumors in 115 patients (68 males, median age 70 years). All procedures
      were carried out by a single experienced colonoscopist. The cases were grouped
      chronologically into three periods: (1st): cases 1-40; (2nd): cases 41-80; and
      (3rd): cases 81-120. RESULTS: The learning curve was the changes in proficiency
      over time. Proficiency was expressed as procedure time per unit area of specimen.
      In the 1st, 2nd and 3rd periods, the proficiencies were 18.9, 12.6 and 12.9
      (min/cm(2) ), respectively. The proficiencies in the 2nd and 3rd periods were
      significantly shorter than in the 1st period (t-test, P < 0.05). The en-bloc
      resection rates of the 1st, 2nd and 3rd periods were 92.5% (37/40), 90% (36/40)
      and 97.5% (39/40), respectively. The en-bloc and R0 resection rates of the 1st,
      2nd and 3rd periods were 85% (34/40), 77.5% (31/40) and 92.5% (37/40),
      respectively. The perforation rates of the 1st, 2nd and 3rd periods were 12.5%
      (5/40), 5% (2/40) and 5% (2/40), respectively. CONCLUSION: Based on our analysis
      of the learning curve, approximately 80 procedures must be carried out to acquire
      skill with ESD for large colorectal tumors. However, approximately 40 procedures
      were sufficient to acquire skill in avoiding perforations during the ESD
      procedure.

PMID- 21175484
TI  - Endoscopic submucosal dissection for colorectal neoplasia.
AB  - AIM: Endoscopic submucosal dissection (ESD) has been positively applied to and
      gradually standardized for early gastric cancer; however, it is not widely used
      in the colorectum because of its technical difficulty. METHODS: To increase the
      safety and ease of carrying out colon ESD, we developed a new scissors-type
      device that we call the stag beetle knife (SBK). Here we report on our efforts to
      assess the efficacy and safety of colon ESD using the SBK. RESULTS: ESD was
      carried out using SBK in 25 patients with colorectal neoplasia. All lesions were
      treated safety and easily, without any unexpected incisions. No delayed
      hemorrhage and perforation occurred. An en-bloc resection and a negative
      resection margin were obtained in all cases. CONCLUSION: ESD using the SBK can be
      carried out with greater ease and safety for colorectal neoplasia.

PMID- 21175485
TI  - Eosinophilic gastroenteritis associated with giant folds.
AB  - We describe a 54-year-old man who presented with right subcostal pain.
      Minocycline had been prescribed to treat pruritus, and the symptoms resolved.
      Subsequently, the patient consulted a local physician because of right subcostal
      pain. Giant folds were found in the greater curvature of the gastric body, and he
      was referred to the Department of Gastroenterology, Kitasato University East
      Hospital. Upper gastrointestinal endoscopy revealed markedly enlarged folds in
      the greater curvature of the stomach, with redness and edematous mucosa in the
      lesser curvature. Biopsy showed marked inflammatory cell infiltration (mainly
      eosinophils), but no atypical cells. Blood tests showed marked eosinophilia and
      elevated immunoglobulin E levels in the serum. The results of various allergic
      examinations were negative, but the clinical course suggested drug-induced
      eosinophilic gastroenteritis, and treatment was started. Minocycline was
      withdrawn without adequate resolution of symptoms. Because the leukocyte and
      eosinophil counts continued to increase, the patient was given suplatast, an anti
      allergic agent. The symptoms and hematological values improved promptly. The
      patient recovered uneventfully, with no recurrence.

PMID- 21175486
TI  - Partial regression of duodenal lesions of intestinal follicular lymphoma after
      antibiotic treatment.
AB  - A 51-year-old man was referred to our hospital because of duodenal lesions of
      lymphoma. Endoscopy showed multiple tiny smooth whitish granules in the second
      portion of the duodenum including the papilla of Vater. Biopsy specimens showed
      medium-sized centrocyte-like cells forming lymphoid follicles, and
      immunohistology showed positive staining for bcl-2 and CD10. A small bowel series
      showed multiple granular lesions extending from the second portion of the
      duodenum to the proximal jejunum and the proximal ileum. On the basis of these
      findings, the tumor was diagnosed as stage I follicular lymphoma (FL). Although
      the patient was negative for Helicobacter pylori, he underwent antibiotic
      treatment. The lesions improved 3 months after antibiotic treatment, but biopsy
      specimens showed residual lymphoma cells. The patient therefore received
      combination chemotherapy with rituximab. Endoscopy 4 months later showed
      regression of FL, and there was no evidence of recurrence during 3 years of
      follow up. The partial regression of duodenal lesions of intestinal FL may be due
      to the effect of antibiotic treatment.

PMID- 21175487
TI  - Direct cholangioscopy using a double-balloon enteroscope: choledochojejunostomy
      with intraductal biliary carcinoma.
AB  - A 75-year-old man who underwent choledochojejunostomy for gallstones 30 years ago
      was hospitalized for general malaise. Abdominal computed tomography revealed
      marked dilation of the intrahepatic bile duct in the right lobe and an image of a
      hypervascular tumor. Endoscopic retrograde cholangiography using double-balloon
      enteroscopy (DBE) showed a filling defect that was localized to the right hepatic
      bile duct. Furthermore, the scope was able to readily pass through the
      anastomosed site of the choledochojejunostomy and, therefore, we observed the
      interior of the bile duct using the same scope. We obtained an image showing a
      whitish, papillary-like tumor, and a biopsy of the tumor rendered the pathology
      of intraductal papillary mucinous carcinoma. Direct cholangioscopy using DBE is a
      useful diagnostic tool, particularly in patients with a past history of
      choledochojejunostomy.

PMID- 21175488
TI  - Supine position endoscopic retrograde cholangiopancreatography in a patient with
      situs ambiguous with polysplenia.
AB  - A 58-year-old woman complained of painless jaundice. The serology showed total
      bilirubin 10.6 mg/dL with direct bilirubin of 7.0 mg/dL. Abdominal computed
      tomography (CT) scan disclosed an abnormal arrangement of the abdominal viscera
      and dilation of the biliary tree. A nearly 1.4 cm-sized periampullary mass was
      seen. These findings are compatible with situs ambiguous with polysplenia and
      were suggestive of a periampullary tumor. Due to her unusual anatomical features,
      the patient underwent an endoscopic retrograde cholangiopancreatography (ERCP) in
      the supine position instead of in the conventional prone position. ERCP showed
      that the common bile duct (CBD) diameter was increased to 20 mm. Microscopic
      findings of the biopsy specimen of papillary mass were compatible with an
      adenocarcinoma of the ampulla of Vater. The clinical stage was stage IA (T1N0M0).
      Eight days later, a papillectomy was carried out by endoscopic snare resection.
      Six months later, follow-up studies, including ERCP, abdominal CT and 18
      fluorodeoxyglucose positron emission tomography ((18) -FDG PET)-CT scan, showed
      no evidence of recurrence. Although the success rate of supine position ERCP may
      be influenced by the extent of the intestinal malrotation and the position of the
      duodenum, we conclude that supine position ERCP can be carried out effectively in
      a patient with situs anomaly.

PMID- 21175489
TI  - Rectal granular-cell tumor difficult to distinguish from carcinoid tumor.
AB  - A 60-year-old man had a positive fecal occult-blood test on a medical check-up.
      Colonoscopy revealed a yellowish-white submucosal tumor 8 mm in diameter in the
      rectum. Endoscopic ultrasonography showed a well-demarcated mass with a
      homogeneous, low-level, internal echo in the second to third layers of the rectal
      wall. A carcinoid tumor was suspected, and the mass was resected endoscopically.
      Histopathological examination revealed a granular-cell tumor. Gastrointestinal
      granular-cell tumors rarely arise in the rectum, and the preoperative diagnosis
      of small lesions is often difficult. In our patient, granular-cell tumor was
      difficult to differentially diagnose because the endoscopic and endoscopic
      ultrasonographic findings closely resembled those of carcinoid tumor.
      Interestingly, the endoscopic characteristics of the rectal granular-cell tumor
      in our patient resembled those of a carcinoid tumor.

PMID- 21175490
TI  - Successful endoscopic hemostasis for ruptured duodenal varices after balloon
      occluded retrograde transvenous obliteration.
AB  - A 75-year-old man with general malaise and appetite loss was transferred to our
      hospital for assessment and treatment of liver failure. Laboratory findings on
      admission showed anemia, and gastroduodenoscopy (GDS) revealed linear esophageal
      varices and tensive duodenal varices (DV) in the second portion of the duodenum.
      Systemic examinations did not reveal any significant lesion capable of explaining
      his anemia, except for DV. Balloon-occluded retrograde transvenous obliteration
      was carried out to prevent DV bleeding. Good pooling of sclerosant was observed
      using two balloon catheters. However, contrast-enhanced computed tomography after
      the procedure revealed no thrombosis in DV, and the patient complained of tarry
      stools before additional therapy. Emergent GDS revealed ruptured DV with fresh
      blood and erosions on the surface. Emergent endoscopic obliteration using the
      tissue adhesive N-butyl-2-cyanoacrylate was carried out and complete hemostasis
      was achieved. Although no rebleeding episodes were observed after emergent
      obliteration, the patient died of sepsis following spontaneous bacterial
      peritonitis 53 days after admission. Autopsy revealed that DV dropped out, and
      the deep vein was replaced by granulation tissue. No signs of thrombi were
      detected, except varices. This autopsy case revealed the difficulty in DV
      management.

PMID- 21175491
TI  - Ultrathin endoscope-assisted ERCP for inaccessible peridiverticular papilla by a
      single-balloon enteroscope in a patient with Roux-en-Y anastomosis.
AB  - We describe a case of successful endoscopic retrograde cholangiopancreatography
      (ERCP) using an ultrathin endoscope for inaccessible peridiverticular papilla by
      a single balloon enteroscopy (SBE) in a patient with Roux-en Y (R-Y). A 73-year
      old man who had total gastrectomy with R-Y for gastric cancer was admitted for
      acute cholangitis. Although the SBE could be advanced to the end of the afferent
      loop, we could not identify a major papilla, although a duodenal diverticula
      could be observed. The enteroscope was replaced with an ultrathin endoscope. The
      ultrathin endoscope allowed the papilla to be detected distal to the side of the
      diverticula. After pre-cutting, the ultraslim endoscope was replaced with a
      conventional forward-viewing endoscope. Eventually, the stones were completely
      removed using a balloon catheter and basket without procedure-related
      complication.

PMID- 21175492
TI  - Successful endoscopic ultrasound-guided fine-needle aspiration of the pelvic
      lesion through the sigmoid colon.
AB  - Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a useful
      modality when the target is a lymph node located in the mediastinum, perigastric
      area or perirectum. Although it is difficult to carry out EUS-FNA of the colon
      using an oblique view linear scope, we report two cases of successful EUS-FNA of
      the lesions via the proximal sigmoid colon using a recently available new convex
      type EUS scope. Case 1 was a 77-year-old Japanese woman noted to have multiple
      lymph node swelling in the para-aortic area and in the pelvis. Case 2 was a 60
      year-old Japanese woman noted to have a large mass in the left lower abdomen. In
      case 1, oral EUS showed no lymph node swelling. In both cases, EUS with forward
      viewing radial echoendoscope was carried out via the anus, and multiple lymph
      node swelling or a large mass was observed near the proximal sigmoid colon. In
      the EUS-FNA for these cases, we used a new convex-type EUS scope that has an
      oblique view, but with a wide-angled optical device giving a view similar to a
      forward one. EUS-FNA was successfully carried out on the lesions. The
      pathological specimen revealed diffuse large B-cell lymphoma in case 1 and
      gastrointestinal stromal tumor (GIST) in case 2.

PMID- 21175493
TI  - Transgastric transhepatic endosonography-guided biliary drainage: histological
      assessment of its sinus tract in an autopsy case.
AB  - Endosonography-guided biliary drainage (ESBD) is gaining attention as a promising
      drainage technique for obstructive jaundice. However, histological changes
      resulting from ESBD have not been well understood. We had an opportunity to
      histologically investigate the influence of ESBD, established between the left
      hepatic duct and the stomach, on the relevant organs in an autopsy case with bile
      duct cancer extending from the pancreatic head to the hepatic hilum with duodenal
      invasion. Localized fibrous connective tissues were present around and along the
      sinus tract, including the connection between the surfaces of the left lobe of
      the liver and the gastric serosa, without hemorrhage, inflammatory changes, or
      cancer invasion. The inside of the ESBD stent was slightly stenotic at the
      intramural portion of the stomach due to proliferation of granulation tissue. No
      bile stasis or abscess was observed in the left lobe. These results are quite
      suggestive of the high safety and efficacy of ESBD with adequate performance.

PMID- 21175494
TI  - Endoscopic pancreatic sphincterotomy plus large-balloon dilation for removal of a
      large impacted pancreatic duct stone (with video).
AB  - Pancreatic duct stones are a common complication of chronic pancreatitis. We
      describe successful endoscopic removal of a large pancreatic duct stone using
      large-balloon dilation in combination with pancreatic sphincterotomy. A 63-year
      old woman was admitted for endoscopic treatment of acute on chronic pancreatitis
      with diabetes and epigastric pain with liver dysfunction due to a large impacted
      stone within the distal main pancreatic duct. Endoscopic pancreatic
      sphincterotomy was carried out using a wire-guided pull-type sphincterotome.
      Although we could carry out a relatively large incision, the stone could not be
      extracted. We therefore carried out papillary dilation using a large balloon
      (diameter 12 to 15 mm) to make room alongside the stone. A 10 * 20-mm white
      pancreatic duct stone was extracted during the process of pulling a dilating
      balloon into the working channel of the endoscope. Eventually, the second stone
      was removed without any procedure-related complication.

PMID- 21175495
TI  - Endoscopic occlusion of cystic duct using N-butyl cyanoacrylate for postoperative
      bile leakage.
AB  - Bile leak after cholecystectomy is well described, with the cystic duct remnant
      the site of the leak in the majority of cases. Endoscopic retrograde
      cholangiopancreatography (ERCP) with biliary stent placement has a high success
      rate in such cases. When ERCP fails, options include surgery, and percutaneous
      and endoscopic transcatheter occlusion of the site of bile leak. Here, we
      describe a case of endoscopic transcatheter occlusion of a persistent cystic duct
      bile leak after cholecystectomy using N-butyl cyanoacrylate glue. A 51-year-old
      man had persistent pain and bilious drainage following a laparoscopic
      cholecystectomy. The bile leak persisted after endoscopic placement of a biliary
      stent for a confirmed cystic duct leak. A repeat ERCP was carried out and the
      cystic duct was occluded with a combination of angiographic coils and N-butyl
      cyanoacrylate glue. The patient's pain and bilious drainage resolved. A follow-up
      cholangiogram confirmed complete resolution of the cystic duct leak and a patent
      common bile duct.

PMID- 21175496
TI  - Splenic rupture following routine colonoscopy.
AB  - Splenic rupture is a life-threatening condition characterized by internal
      hemorrhage, often difficult to diagnose. Colonoscopy is a gold standard routine
      diagnostic test to investigate patients with gastrointestinal symptoms as well as
      to those on the screening program for colorectal cancer. Splenic injury is
      seldomly discussed during consent for colonoscopy, as opposed to colonic
      perforation, as its prevalence accounts for less than 0.1%. A 66-year-old
      Caucasian woman with no history of collagen disorder was electively admitted for
      routine colonoscopy for surveillance of adenoma. She was admitted following the
      procedure for re-dosing of warfarin, which was stopped prior to the colonoscopy.
      The patient was found collapsed on the ward the following day with clinical shock
      and anemia. Computed tomography demonstrated grade 4 splenic rupture. Immediate
      blood transfusion and splenectomy was required. Splenic rupture following routine
      colonoscopy is extremely rare. Awareness of it on this occasion saved the
      patient's life. Despite it being a rare association, the seriousness warrants
      inclusion in all information leaflets concerning colonoscopy and during its
      consent.

PMID- 21175497
TI  - Small gastrointestinal stromal tumor of the stomach showing rapid growth and
      early metastasis to the liver.
AB  - A 65-year-old man received upper gastrointestinal endoscopy. At that time, no
      abnormalities were identified in the stomach except for a submucosal tumor
      approximately 1 cm in maximal diameter at the gastric cardia. Two months later,
      he developed tarry stools and anemia. Colonoscopy revealed no abnormal findings
      in the colon or terminal ileum. Upper gastrointestinal endoscopy was re-evaluated
      in our hospital. Macroscopically, the previously detected submucosal tumor had
      grown to 3.0 cm in maximal diameter and the tumor was exposed by extensive
      ulceration. Biopsy specimens of the lesion indicated KIT-positive
      gastrointestinal stromal tumor (GIST) with a probability of high risk. Total
      gastrectomy was carried out and the resected GIST was found to comprise spindle
      shaped tumor cells with 23 mitoses in 10 high-power fields. Mutation of the c-kit
      gene was studied using the surgical specimens, and deletion of five amino acids
      from codons 554-558 in exon 11 was detected. Liver metastasis was found 6 months
      postoperatively, and molecular target therapy was carried out. However, the
      patient died 2 years after the finding of liver metastasis.

PMID- 21175498
TI  - Congenital hepatic fibrosis without any symptoms as diagnosed by laparoscopy.
AB  - The present report represents the case of a 36-year-old woman with congenital
      hepatic fibrosis (CHF). She was admitted to our hospital because of gastric
      varices. She was asymptomatic and her liver function tests were within normal
      limits. Computed tomography showed hepatomegaly, splenomegaly and collateral
      circulation, but no evidence of liver cirrhosis. Real-time tissue elastography
      suggested severe fibrosis of the liver. Laparoscopy showed wide and discrete
      white markings on the surface of the liver and she was diagnosed with CHF based
      on the histological examination. The findings obtained from elastography and
      laparoscopy were useful for making the diagnosis of CHF.

PMID- 21175499
TI  - Usefulness of endoscopic treatment for duodenal adenoma.
AB  - In recent years, due to the increasing prevalence of upper gastrointestinal
      endoscopy, there have been an increasing number of reports on duodenal adenoma
      and early stage cancer. However, endoscopic techniques for the resection of
      duodenal adenomas are difficult, due to the anatomical features of the duodenum,
      and the long distance to the lesion. There have only been a few reports on the
      use of endoscopic techniques for duodenal adenomas compared to those focused on
      the stomach and large intestine. For duodenal adenomas, we used a conventional
      endoscope for lesions proximal to the major duodenal papilla, and a short-type
      double balloon endoscope for lesions distal to the papilla. The en-bloc resection
      rate was 93.8%. There was only one case of microperforation. Endoscopic
      manipulation is considered difficult in the deep areas of the duodenum, but
      double balloon endoscopy enabled stable manipulation and successful resection of
      the tumor in the majority of cases.

PMID- 21175500
TI  - Anchor clip technique helps in easy prevention of post-polypectomy hemorrhage of
      large colonic polyps.
AB  - Large colonic polyps have large vessels, which often cause post-polypectomy
      hemorrhage. Some of the stalks of large pedunculated polyps are formed by the
      weight of the polyps and disappear after polypectomy. There are some reports
      suggesting that pre-ligation with Endoloop(R) may minimize the risk of post
      polypectomy hemorrhage. However, the current density increases more at the site
      of pre-ligation as compared with that at the site of polypectomy, because
      polypectomy is carried out with gradual snaring. This implies that burn injury
      may also occur at the site of pre-ligation, causing the loss of pre-ligation and,
      consequently, post-polypectomy hemorrhage. Ligation of stalks after polypectomy
      is very difficult. The Endoloop(R) rolls back when it is tightened, because of
      the lack of torsional stiffness. We have developed a simple and improved post
      polypectomy ligation technique using the Anchor clip. Before polypectomy, an
      Endoclip(R) is placed partially at the base of the pedunculated polyp. When the
      stalk is tightened completely with the Endoclip(R) before polypectomy, burn
      injury occurs around the Endoclip(R) . The Anchor clip at the base of the
      pedunculated polyp holds the stalk after polypectomy and the constricted part
      formed by the Anchor clip prevents the rolling up of the Endoloop(R) and helps in
      easy ligation of the stalk. We have used the Anchor clip for 50 patients.
      Application of the Endoloop(R) after polypectomy was impossible in two patients.
      The remaining 48 patients underwent Endoloop(R) -assisted polypectomy with the
      Anchor clip, and in none of the cases did bleeding occur after polypectomy.

PMID- 21175501
TI  - Diagnostic yield of double-balloon enteroscopy with intestinal juice analysis for
      intestinal strongyloidiasis.
AB  - Strongyloidiasis is relatively common in tropical and subtropical areas. Most
      patients with Strongyloides stercoralis hyperinfection are immunocompromised,
      most commonly from corticosteroids or human T-cell lymphoma virus type 1 (HTLV-1)
      infection. We encountered a patient with HTLV-1 infection accompanied by
      paralytic ileus, in whom strongyloidiasis in the duodenum and jejunum was
      disclosed by esophagogastroduodenoscopy (EGD) and double-balloon enteroscopy
      (DBE). Until the age of 7 years, he lived on Amami-Oshima Island, Japan, where
      both S. stercoralis and HTLV-1 are endemic. EGD and peroral DBE disclosed white
      villi, edematous mucosa, and the disappearance of folds in the duodenum and
      jejunum. Biopsy specimens from the white villi in the duodenum and jejunum
      revealed S. stercoralis larvae. In both duodenal and jejunal juice, the
      rhabditiform larvae moved around. Because the larvae invade the lymph vessels,
      resulting in lymphangiectasia in edematous enteritis, the appearance of white
      villi may reflect villous atrophy/destruction and mucosal edema. Although our
      patient revealed no eosinophilia and negative stool specimens for parasites or
      ova, EGD and DBE with multiple biopsies and intestinal juice analysis are
      valuable diagnostic tools for strongyloidiasis.

PMID- 21175502
TI  - Pseudomembranous colitis complicating ulcerative colitis.
AB  - Clostridium difficile toxin (CD toxin) causes antibiotic-associated colitis, or
      pseudomembranous colitis (PMC). Although CD toxin is sometimes found in the
      stools of patients with ulcerative colitis (UC), UC is rarely complicated by PMC.
      We report herein a case of PMC complicating UC, and present a review of the
      literature. A 71-year-old woman was diagnosed as having UC of the left colon, and
      treated with prednisolone and mesalazine. Later, however, lumbar spinal stenosis
      was also detected. After surgery for lumbar spinal stenosis, she suffered
      postoperative infection of the lumbar region. After 3-week treatment with
      antibiotics, she developed diarrhea, bloody stools, and abdominal pain.
      Colonoscopy revealed PMC of the cecum, ascending colon, sigmoid colon, and
      rectum. Stools were positive for CD toxin. As cefotiam hydrochloride,
      levofloxacin hydrate (LVFX), and prednisolone were suspected as the causative
      agents, she was treated with 1.5 g vancomycin (VCM) daily for 2 weeks without
      ceasing LVFX. Her symptoms improved, and colonoscopy confirmed resolution of PMC.
      The possibility of PMC should be considered in UC patients treated with
      antibiotics, immunosuppressive agents or corticosteroids who complain of
      gastrointestinal symptoms. These patients should be thoroughly investigated by
      several modalities, including colonoscopy and CD toxin testing.

PMID- 21175503
TI  - Current status in the occurrence of postoperative bleeding, perforation and
      residual/local recurrence during colonoscopic treatment in Japan.
AB  - Bleeding, perforation, and residual/local recurrence are the main complications
      associated with colonoscopic treatment of colorectal tumor. However, current
      status regarding the average incidence of these complications in Japan is not
      available. We conducted a questionnaire survey, prepared by the Colorectal
      Endoscopic Resection Standardization Implementation Working Group, Japanese
      Society for Cancer of the Colon and Rectum (JSCCR), to clarify the incidence of
      postoperative bleeding, perforation, and residual/local recurrence associated
      with colonoscopic treatment. The total incidence of postoperative bleeding was
      1.2% and the incidence was 0.26% with hot biopsy, 1.3% with polypectomy, 1.4%
      with endoscopic mucosal resection (EMR), and 1.7% with endoscopic submucosal
      dissection (ESD). The total incidence of perforation was 0.74% (0.01% with the
      hot biopsy, 0.17% with polypectomy, 0.91% with EMR, and 3.3% with ESD). The total
      incidence of residual/local recurrence was 0.73% (0.007% with hot biopsy, 0.34%
      with polypectomy, 1.4% with EMR, and 2.3% with ESD). Colonoscopic examination was
      used as a surveillance method for detecting residual/local recurrence in all
      hospitals. The surveillance period differed among the hospitals; however, most of
      the hospitals reported a surveillance period of 3-6 months with mainly
      transabdominal ultrasonography and computed tomography in combination with the
      colonoscopic examination.

PMID- 21175504
TI  - Endoscopic ultrasonography-guided gastrostomy tube placement from the stomach.

PMID- 21175506
TI  - The role of the Society for Academic Emergency Medicine in the development of
      guidelines and performance measures.
AB  - Measurement of adherence to clinical standards has become increasingly important
      to the practice of emergency medicine (EM). In recent years, along with a
      proliferation of evidence-based practice guidelines and performance measures,
      there has been a movement to incorporate measurement into reimbursement
      strategies, many of which affect EM practice. On behalf of the Society for
      Academic Emergency Medicine (SAEM) Guidelines Committee 2009-2010, the purposes
      of this document are to: 1) differentiate the processes of guideline and
      performance measure development, 2) describe how performance measures are
      currently and will be used in pay-for-performance initiatives, and 3) discuss
      opportunities for SAEM to affect future guideline and performance measurement
      development for emergency care. Specific recommendations include that SAEM
      should: 1) develop programs to sponsor guideline and quality measurement
      research; 2) increase participation in the process of guideline and quality
      measure development, endorsement, and maintenance; 3) increase collaboration with
      other EM organizations to review performance measures proposed by organizations
      outside of EM that affect emergency medical care; and 4) answer calls for
      participation in the selection and implementation of performance measures through
      The Joint Commission and the Centers for Medicare and Medicaid Services (CMS).

PMID- 21175507
TI  - A traveler caught in the "thick" of things: A CPC case of a young African
      American female with headaches.

PMID- 21175508
TI  - The heart point sign: description of a new ultrasound finding suggesting
      pneumothorax.

PMID- 21175509
TI  - Bag-mask ventilation educational video.

PMID- 21175510
TI  - Posterior ankle dislocation reduction.

PMID- 21175511
TI  - Single-operator sterile sheathing of ultrasound probes for ultrasound-guided
      procedures.

PMID- 21175512
TI  - Use of intranasal fentanyl for the relief of pediatric orthopedic trauma pain.
AB  - OBJECTIVES: The objective was to evaluate the use of a single 2 MUg/kg dose of
      intranasal fentanyl as analgesia for painful orthopedic injuries in children
      presenting to a pediatric emergency department (ED). METHODS: This was a
      prospective, nonblinded interventional trial, in a convenience sample of patients
      3 to 18 years of age seen in a tertiary care pediatric ED. All had clinically
      suspected fractures and were treated between July and November 2006. Eligible
      patients had moderate to severe pain based on initial pain scores using the Wong
      Baker Faces Scale (WBS) for patients aged 3-8 years or the Visual Analog Scale
      (VAS) for patients aged 9-18 years. All enrolled patients received fentanyl via
      intranasal atomization. Pain scores were obtained at baseline and at 10, 20, and
      30 minutes after intranasal fentanyl administration. Satisfaction scores were
      obtained using a 100-mm VAS. Vital signs and adverse events were recorded.
      RESULTS: Eighty-one patients were enrolled, 28 in the VAS group and 53 in the WBS
      group. The mean patient age was 8 years. Fracture locations included forearm, 38
      (47%); supracondylar, 16 (20%); clavicle, 7 (9%); tibia/fibula, 5 (6%); and
      other, 15 (18%). In the WBS group, the median pain scores decreased from five
      faces (interquartile range [IQR] = 4-6) at baseline to three faces (IQR = 2-5) at
      10 minutes, two faces (IQR = 1-4) at 20 minutes, and two faces (IQR = 1-3) at 30
      minutes. The mean pain score in the VAS group at baseline was 70 mm (95%
      confidence interval [CI] = 63 to 77 mm). In this group, the pain scores decreased
      by a mean of 21 mm (95% CI = 14 to 28 mm) at 10 minutes, 25 mm (95% CI = 15 to 34
      mm) at 20 minutes, and 27 mm (95% CI = 16 to 37 mm) at 30 minutes. Mean
      satisfaction scores were 79 mm for providers, 74 mm for parents, and 62 mm for
      patients. No adverse events were recorded. CONCLUSIONS:   Intranasal fentanyl at
      a dose of 2 MUg/kg provides effective analgesia for pediatric ED patients with
      painful orthopedic trauma within 10 minutes of administration.

PMID- 21175513
TI  - Tissue Doppler of early mitral filling correlates with simulated volume loss in
      healthy subjects.
AB  - OBJECTIVES: The accurate noninvasive assessment of preload in emergency
      department (ED) patients remains elusive. Point-of-care ultrasound (US) imaging,
      particularly evaluation of the inferior vena cava (IVC), has been shown to be
      qualitatively helpful. Doppler and tissue Doppler are now routinely available on
      ED US equipment, but few studies have looked at the correlation of dynamic
      changes in these parameters in a controlled model of hypovolemia. Our objective
      was to examine the correlation of Doppler parameters to simulated volume loss in
      healthy subjects using a lower-body negative pressure (LBNP) model and to compare
      these measurements to commonly used IVC measurements of preload. METHODS: Twelve
      paid volunteers with no known cardiovascular disease between the ages of 23 and
      31 years old (mean +/- SD = 25.5 +/- 2.5 years old) were recruited. Hypovolemia
      was simulated using graduated LBNP levels with measurements taken at 0, -30, and 
      60 mm Hg and lower pressures as tolerated. Vital signs were monitored in all
      patients. US measurements recorded at each negative pressure level included IVC
      maximum (IVC(max)) and minimum (IVC(min)) dimensions; early (E) and late (A)
      transmitral filling velocities using pulsed-wave spectral Doppler; and early (E')
      and late (A') tissue Doppler velocities at the septal ((sep)) and lateral ((lat))
      mitral annulus, using pulsed-wave tissue Doppler. RESULTS: Lower-body negative
      pressure correlated significantly and positively within subjects for all US
      parameters except for the A filling wave. E'(lat) and E'(sep) showed the
      strongest correlation with R2 values of 0.749 (95% confidence interval [CI] =
      0.577 to 0.854) and 0.738 (95% CI = 0.579 to 0.875) respectively, followed by
      A'(sep) 0.674 (95% CI = 0.416 to 0.845), IVC(max) 0.638 (95% CI = 0.425 to
      0.806), A'(lat) 0.547 (95% CI = 0.280 to 0.802), IVC(min) 0.512 (95% CI = 0.192
      to 0.777), and E 0.478 (95% CI = 0.187 to 0.762). Ratios correlated only
      moderately with LBNP level, including E/ E'(lat) R2 of 0.430 (95% CI = 0.131 to
      0.706), E/ E'(sep) 0.416 (95% CI = 0.183 to 0.686), and IVC collapsibility index
      (IVC(CI)) 0.201 (95% CI = 0.003 to 0.681). Vital signs, including heart rate and
      blood pressure, did not vary significantly with LBNP levels. CONCLUSIONS: In this
      pilot study of healthy subjects, tissue Doppler assessment of early diastolic
      filling correlated most strongly with simulated hypovolemia.

PMID- 21175514
TI  - Closed reduction of distal forearm fractures by pediatric emergency physicians.
AB  - OBJECTIVES: The objective of this study was to determine if there exist
      differences in length of stay (LOS) in the emergency department (ED) and need for
      reintervention to restore alignment after distal forearm fracture reduction by
      pediatric emergency physicians (EPs) versus postgraduate year 3 or 4 orthopedic
      residents. METHODS: In a prospective trial at a busy urban pediatric ED, children
      with closed distal forearm fractures that met predefined criteria for
      manipulation were randomized to treatment by a postgraduate year 3 or 4
      orthopedic resident or by a pediatric EP who had received focused training in
      forearm fracture reduction. Prereduction, postreduction, and follow-up
      radiographs were evaluated by an attending pediatric orthopedic surgeon who was
      unaware of the assigned group. The following outcomes were assessed: LOS during
      the initial ED encounter, adequacy of alignment immediately postreduction and at
      follow-up visits after discharge from the ED, the need for remanipulation,
      unscheduled ED visits, and radiographic healing at 6-8 weeks after injury.
      RESULTS: A total of 103 children were randomized into the pediatric EP (52
      patients, mean age 9.1 years) and orthopedic resident (51 patients, mean age 9.7
      years) groups. Patients in the two groups were similar in age, involvement of the
      physes, degree of angulation, percentage of displacement, and need for procedural
      sedation. The mean LOS in the ED was 4.5 hours in the pediatric EP group versus
      5.0 hours in the orthopedic resident group (difference in means -0.5 hours, 95%
      confidence interval [CI] = -1.26 to 0.37 hours). Remanipulation was required in 4
      of 48 (8.3%) in the pediatric EP group versus 6 of 48 (12.5%) in the orthopedic
      resident group (odds ratio [OR] = 0.64; 95% CI = 0.16 to 2.67). Unscheduled ED
      visits for cast-related problems occurred in 6 of 51 (11.8%) in the pediatric EP
      group and 4 of 52 (7.7%) in the orthopedic resident group (OR = 1.59; 95% CI =
      0.38 to 6.39). None of these patients with unscheduled ED visits developed
      compartment syndrome or required admission. CONCLUSIONS: Length of stay in the ED
      and clinical outcomes after closed reduction of forearm fractures by trained
      pediatric EPs are comparable to those after closed reduction by orthopedic
      residents.

PMID- 21175515
TI  - Vernakalant hydrochloride: A novel atrial-selective agent for the cardioversion
      of recent-onset atrial fibrillation in the emergency department.
AB  - OBJECTIVES: Vernakalant is a relatively atrial-selective antiarrhythmic agent
      that has been shown to successfully convert atrial fibrillation (AF) to normal
      sinus rhythm for some patients whose onset of dysrhythmia occurred less than 7
      days previously. This study sought to evaluate the efficacy and safety of
      vernakalant for patients with recent-onset AF. METHODS: This was a post hoc
      analysis of patients with recent-onset AF (> 3 to <= 48 hours) enrolled in the
      double-blind, placebo-controlled Atrial arrhythmia Conversion Trial (ACT) I and
      the open-label ACT IV trials. The studies enrolled adults presenting with AF to
      78 emergency departments (ED) and cardiac clinics in six countries. Patients
      received a 10-minute intravenous infusion of vernakalant or placebo, followed by
      an additional infusion if necessary. Efficacy assessments included conversion to
      sinus rhythm within 90 minutes and median time to conversion. Safety evaluations
      included telemetry, Holter monitoring, and adverse events (AEs). RESULTS: Of the
      290 patients, 229 received vernakalant, 61 received placebo, and the overall mean
      age was 59 years. The vernakalant and placebo groups were similar. Of all
      patients given vernakalant, 136 (59.4%) converted to sinus rhythm within 90
      minutes, compared with three (4.9%) placebo patients. The median time to
      conversion with vernakalant was 12 minutes (interquartile range = 7-24.5
      minutes). Clinically significant bradycardia and hypotension were uncommon, and
      no cases of torsade de pointes or ventricular fibrillation occurred. CONCLUSIONS:
      Vernakalant rapidly converted recent-onset AF to sinus rhythm in over half of
      patients, was well tolerated, and has the potential to offer an important
      therapeutic option for rhythm control of recent-onset AF in the ED.

PMID- 21175516
TI  - Triaging herpes zoster ophthalmicus patients in the emergency department: do all
      patients require referral?
AB  - OBJECTIVES: The objective was to assess the predictive value of clinical signs
      and symptoms of herpes zoster ophthalmicus (HZO) for development of moderate to
      severe eye disease. METHODS: This was a prospective cohort multicenter study of
      54 patients referred to the ophthalmology service after presenting to the
      emergency department (ED) or primary care clinic with a zosteriform rash of less
      than 10 days' duration. Upon referral to ophthalmology, easily assessable
      clinical signs and symptoms were documented. A complete ocular exam was then
      performed. Patients were followed for 2 months. RESULTS: Twenty-three patients
      (43%) developed moderate to severe disease as defined by corneal or intraocular
      involvement. Eye redness and rash in the supratrochlear nerve distribution had a
      statistically significant association with clinically relevant eye disease. All
      23 patients who developed moderate to severe eye disease presented with a red
      eye. Hutchinson's sign (nasociliary nerve involvement) was not predictive of
      clinically relevant eye disease. CONCLUSIONS: Eye redness was 100% sensitive for
      predicting moderate to severe eye disease in this sample of patients and should
      necessitate immediate referral for ophthalmologic assessment. Patients lacking
      eye redness, even with a positive Hutchinson's sign, may not require immediate
      specialist consultation. All patients not being referred require careful
      instructions to seek further care should they develop any concerning eye symptoms
      such as redness, pain, photophobia, or visual disturbance.

PMID- 21175518
TI  - Identifying key metrics for reducing premature departure from the pediatric
      emergency department.
AB  - OBJECTIVES: Approximately 2% to 5% of children presenting to pediatric emergency
      departments (PEDs) leave prior to a complete evaluation. This study assessed risk
      factors for premature departure (PD) from a PED to identify key metrics and
      cutoffs for reducing the PD rate. METHODS: A 3-year cohort (June 2004-May 2007)
      of children presenting to a PED was evaluated. Children were excluded if they
      presented for psychiatric issues, were held awaiting hospital admission in the
      PED due to a lack of inpatient beds, were more than 21 years old, or died before
      disposition. Univariate analyses, multivariable logistic regression, and
      recursive partitioning were used to identify factors associated with PD. A fourth
      year of data (June 2007-May 2008) was used for validation and sensitivity
      analysis. RESULTS: There were 132,324 patient visits in the 3-year derivation
      data set with a 3.8% PD rate, and 45,001 visits in the fourth-year validation
      data set with a 4.3% PD rate. PDs were minimized when average wait time was below
      110 minutes, concurrent PDs were fewer than two, and average length of stay (LOS)
      was less than 224 minutes in the derivation set, with similar results in the
      validation set. When these metrics were exceeded, PD rates were over 10% among
      low-acuity patients. These findings were robust across a broad range of
      assumptions during sensitivity analysis. CONCLUSIONS: The authors identified five
      key metrics associated with PD in the PED: average wait time, average LOS,
      acuity, concurrent PDs, and arrival rate. Operational cutoffs for these metrics,
      determined by recursive partitioning, may be useful to physicians and
      administrators when selecting specific interventions to address PDs from the PED.

PMID- 21175517
TI  - North American practice patterns of intravenous magnesium therapy in severe acute
      asthma in children.
AB  - OBJECTIVES: Although intravenous (IV) magnesium (Mg) can decrease
      hospitalizations in children with severe acute asthma, its use is often limited
      to resistant disease, and disposition may be determined prior to its use. Since
      knowledge about practice patterns of IV Mg would enhance knowledge translation
      and guide future research, we surveyed pediatric emergency physicians with
      interest in clinical research to determine the frequency, indications, adverse
      events, and barriers to use of IV Mg in children with severe acute asthma.
      METHODS: A cross-sectional online survey of two national pediatric emergency
      physician associations in Canada and the United States was conducted using a
      modified Dillman technique. RESULTS: Response rates were 124 of 180 (69%) in
      Canada and 75 of 108 (69%) in the United States. Although 88% of participants
      report knowing that Mg is effective, only 14 of 199 (7%) give it to prevent
      hospitalizations and 142 of 199 (71%) give it to prevent admissions to the
      intensive care unit (ICU). Thirty-eight percent of respondents use Mg in < 5% of
      stable children with severe acute asthma, while 79% use it in 50% or more of the
      ICU candidates with concern about impending respiratory failure. Seventy-nine
      percent of the participants report that < 5% of their patients given Mg are
      discharged home from the ED. Twenty-four percent of respondents who administer Mg
      have encountered associated severe hypotension requiring therapy, and 2% have
      witnessed-related apnea. Factors affecting Mg use include concern about side
      effects expressed by 24% of physicians and a belief that IV therapy is not
      necessary, expressed by 31%. CONCLUSIONS: Intravenous Mg appears to be uncommonly
      used in stable children with severe acute asthma and does not frequently play a
      role in reducing hospitalizations. Further research to justify its enhanced use
      and to better establish its true adverse effect profile is indicated.

PMID- 21175519
TI  - Current practice and tolerance for risk in performing procedural sedation and
      analgesia on children who have not met fasting guidelines: a Canadian survey
      using a stated preference discrete choice experiment.
AB  - OBJECTIVES: The objectives were to explore the tolerance of pediatric emergency
      medicine (PEM) physicians for risk in choosing when to perform procedural
      sedation and analgesia (PSA) and to describe adherence to preprocedural fasting
      guidelines and factors affecting the physicians' decisions. METHODS: A survey of
      Canadian PEM physicians who perform PSA was conducted. Respondents were asked
      about their PSA practices. Risk tolerance was assessed using an economics-based
      stated preference elicitation method called a discrete choice experiment (DCE).
      Using a hypothetical clinical situation of a healthy child needing PSA, three
      fasting scenarios (ingestion of full meal < 2 hours ago, full meal between 2 and
      4 hours ago, liquids less than 1 hour ago) were created. For each fasting
      scenario, 16-choice questions with varying numeric risks of major and minor
      adverse events were presented and respondents were asked whether they would
      administer PSA now or wait for guidelines to be met. In this exploratory study,
      choice data were analyzed using multivariate regression analysis, and preliminary
      inferential statistics are presented. RESULTS: A total of 114 (63.6%) completed
      surveys were returned. Respondents were 54% male, were in practice for a median
      of 6-10 years, and reported following fasting guidelines 53% of the time. Most
      had institutional fasting policies (70%), used ketamine (in 78% of PSA by 95% of
      users), and identified patient variables (prolonged pain, parental concern) as
      more important than environmental variables (patient flow, use of resources) in
      deciding when to administer PSA. Both major and minor risks of adverse events
      affected the choice of whether to do immediate PSA or wait until fasting
      guidelines were met. A 0.1-percentage-point increase in the probability of a
      major adverse event reduced physician likelihood of performing immediate PSA
      before meeting fasting guidelines by 17.6 percentage points. In comparison, a 10
      percentage-point increase in the probability of a minor adverse event reduced
      physician likelihood of performing immediate PSA by 17.2%. Respondents were less
      likely to perform PSA immediately if a child had a full meal < 2 hours ago versus
      2-4 hours ago or liquids < 1 hour ago. Sex, highest level of postgraduate
      training, frequency of performing PSA, and experience with a prior adverse event
      did not affect the choice to do immediate PSA. Years in practice affected the
      decision, with those in practice for 6-10 years more likely to perform immediate
      PSA than those in practice for shorter or longer. Those who reported having an
      institutional fasting policy were less likely to perform immediate PSA.
      CONCLUSIONS: These results suggest that fasting guidelines are not strictly
      adhered to in Canadian pediatric emergency departments (EDs) currently, and there
      is some willingness of physicians to change their sedation practice in light of
      evidence from hypothetical surveillance data about risks. On the other hand, some
      physicians suggest that they will follow guidelines regardless of how low the
      estimated risk is from surveillance data. An understanding of how physicians
      respond to evidence about small risks and how the information is best understood
      by this population is interesting for knowledge translation if evidence-based
      practice guidelines for procedural sedation in the ED are developed in the
      future.

PMID- 21175520
TI  - The association of controlling pseudoephedrine availability on methamphetamine
      related emergency department visits.
AB  - OBJECTIVES: Methamphetamine is a drug of abuse that has been manufactured locally
      by chemical conversion from the decongestant pseudoephedrine. In July 2006, an
      Oregon state law was enacted to establish pseudoephedrine as a schedule III drug
      and make it available by prescription only. This study sought to determine if
      this legislation altered the number of emergency department (ED) visits that are
      related to methamphetamine use. METHODS: This was a retrospective analysis of a
      database created during a prospective study aimed at determining the effect of
      methamphetamine on ED visits. That prospective study was 1 year in duration and
      required ED clinicians to determine whether a patient's visit was related to
      methamphetamine and if the patient had confirmed use of methamphetamine. The
      clinicians received initial and continued education and training on
      methamphetamine during the study period. The questions were asked at every ED
      visit during the study period and were electronically linked to the patient's
      disposition and could not be circumvented. The study period was divided into
      prelegislation (February 5, 2006, to June 30, 2006) and postlegislation periods
      (July 1, 2006, to February 5, 2007). RESULTS: Over the 1-year study period,
      37,625 patients were enrolled, 1.90% (n = 714) of patients had methamphetamine
      related ED visits (MREDVs), and 1.65% (n = 620) had confirmed methamphetamine
      use. Patients with MREDVs were more likely than patients with non-MREDVs to be
      white and uninsured. The number and proportion of weekly MREDVs significantly
      decreased from the prelegislation period to the postlegislation period (mean
      number of weekly visits, 18.0 vs. 11.3, p = 0.001; mean proportion of weekly
      visits, 2.3% vs. 1.6%, p = 0.003). The number and proportion of weekly confirmed
      users of methamphetamine also significantly decreased during the study period
      (mean number of weekly users, 14.6 vs. 10.3, p = 0.004; mean proportion of weekly
      users, 1.9% vs. 1.4%, p = 0.017). There were no significant differences in the
      diagnoses of MREDVS between the pre- and postlegislation periods. CONCLUSIONS:
      This study found an association between the enactment of legislation that limits
      pseudoephedrine availability and a decrease in MREDVs and confirmed users of
      methamphetamine in the study ED.

PMID- 21175522
TI  - Serum ischemia-modified albumin levels in an experimental acute mesenteric
      ischemia model.
AB  - OBJECTIVES: This experimental study aimed to assess the changes in the levels of
      serum ischemia-modified albumin (IMA) and interleukin-6 (IL-6) by time in cases
      of acute mesenteric ischemia due to superior mesenteric artery occlusion.
      METHODS: Twenty-one New Zealand rabbits were randomly divided into three groups.
      Blood samples were collected at hours 0, 1, 3, and 6 from animals in a control
      group; a sham group following a simple laparotomy; and in an ischemia group
      following superior mesenteric artery ligation. All blood samples were analyzed
      for serum IMA and IL-6 levels, and then the time-dependent changes of biomarkers
      were investigated. RESULTS: The serum IMA levels of the ischemia group at hours 3
      and 6 were significantly higher than those of the control and sham groups (hour
      3, p = 0.017; hour 6, p = 0.001). The increase in serum IL-6 levels in the
      ischemia group at hours 1, 3, and 6 compared to the control and sham groups was
      also significant (hour 1, p = 0.002; hour 3, p = 0.003; hour 6, p = 0.003).
      CONCLUSIONS: IMA may be helpful as a marker in the diagnosis of acute mesenteric
      ischemia; however, its diagnostic value and use as a routine biochemical test
      should be assessed in further studies.

PMID- 21175521
TI  - Survival benefit of transfer to tertiary trauma centers for major trauma patients
      initially presenting to nontertiary trauma centers.
AB  - OBJECTIVES: Recent evidence suggests a measurable reduction in mortality for
      patients transferred from a nontertiary trauma center (Level III or IV) to a
      Level I trauma center, but not for those transferred to a Level II trauma center.
      Whether this can be generalized to a predominantly rural region with fewer
      tertiary trauma care resources is uncertain. This study sought to evaluate
      mortality differences for patients initially presenting to nontertiary trauma
      centers in a predominantly rural region depending on transfer status. METHODS:
      This was a retrospective cohort study of patients initially presenting to 104
      nontertiary trauma centers in Oklahoma and meeting the state's criteria for major
      trauma. Patients dying within 1 hour of emergency department (ED) arrival at the
      nontertiary trauma center were excluded. The exposure variable of interest was
      admission status, which was categorized as either transfer to a tertiary (Level I
      or II) trauma center within 24 hours or admission to a nontertiary trauma center.
      Propensity scores were used to minimize the selection bias inherent in the
      decision to admit or transfer a patient for higher-level care. Multiple logistic
      regression was used to generate three propensity score models: probability of
      transfer to either a Level I or II, Level I only, and Level II only. Propensity
      scores were then included as a covariate in multivariable Cox regression models
      assessing outcome differences between admitted and transferred patients. The
      outcome of interest was 30-day mortality, defined as death at either the
      nontertiary trauma center or the tertiary trauma center within 30 days of arrival
      at the initial Level III/IV center's ED. RESULTS: A total of 6,229 patients met
      study criteria, of whom 2,669 (43%) were transferred to tertiary trauma centers.
      Of those transferred, 1,422 patients (53%) were transferred to a Level I trauma
      center. Crude mortality was lower for patients transferred to tertiary trauma
      centers compared to those remaining at nontertiary trauma facilities (hazard
      ratio [HR] = 0.59; 95% confidence interval [CI] = 0.48 to 0.72). After adjusting
      for the propensity to be transferred, Injury Severity Score (ISS), presence of
      severe head injury, and age, transfer to a tertiary trauma center was associated
      with a significantly lower 30-day mortality (HR = 0.38; 95% CI = 0.30 to 0.50)
      compared to admission and treatment at a nontertiary trauma center. The observed
      survival benefit was similar for patients transferred to a Level I trauma center
      (HR = 0.36; 95% CI = 0.20 to 0.4) and those transferred to a Level II center (HR
      = 0.45; 95% CI = 0.33 to 0.61). CONCLUSIONS: This study suggests a survival
      benefit among patients initially presenting to nontertiary trauma centers who are
      subsequently transferred to tertiary trauma centers compared to those remaining
      in nontertiary trauma centers, even after adjusting for variables affecting the
      likelihood of transfer. Although this survival benefit was larger for patients
      treated at a Level I trauma center, Level II trauma centers in a region with few
      tertiary trauma resources demonstrated a measurable benefit as well.

PMID- 21175524
TI  - The learning curve of resident physicians using emergency ultrasonography for
      cholelithiasis and cholecystitis.
AB  - BACKGROUND: Emergency department bedside ultrasonography (EUS) can expedite
      treatment for patients. However, it is unknown how much experience is required
      for competency in the sonographic diagnosis of cholelithiasis and cholecystitis.
      OBJECTIVES: The objective was to assess the learning curve of physicians training
      in right upper quadrant (RUQ) EUS. METHODS: This was a prospective study at an
      urban, academic emergency department from August 1999 to July 2006. Patients with
      suspected biliary tract disease underwent RUQ EUS followed by abdominal ultra
      sonography (AUS) by the Department of Radiology. Results of EUS were compared to
      AUS using a predesigned, standardized data sheet. RESULTS: A total of 1,837
      patients underwent EUS by 127 physicians. The overall sensitivity and specificity
      of EUS for cholelithiasis were 84% (95% confidence interval [CI] = 81% to 86%)
      and 86% (95% CI = 83% to 88%), respectively. The overall sensitivity of EUS for
      ductal dilation, gallbladder wall thickening, pericholecystic fluid, and sludge
      were each < 60%. When analyzing the EUS test characteristics, for every increase
      in 10 examinations up to 50 examinations, there was no significant improvement in
      the sensitivity or specificity for any of these sonographic findings. Moreover,
      on probit regression analysis, accounting for clustering or correlation among the
      examinations performed by each of the operators, there was no improvement for
      detecting any of the sonographic findings except for pericholecystic fluid for
      every 10 additional examinations performed. CONCLUSIONS: When adjusting for
      operator dependence, performing up to 50 EUS examinations appears to have little
      effect on the accuracy of RUQ EUS. Rather than simply requiring an arbitrary
      number of examinations, another method of competency assessment may be necessary.

PMID- 21175523
TI  - Comparative analysis of the cardioprotective properties of opioid receptor
      agonists in a rat model of myocardial infarction.
AB  - OBJECTIVES: This study was conducted to test the hypothesis that opioid receptor
      (OR)-mediated cardioprotection is agonist specific when administered prior to
      coronary artery occlusion and reperfusion in a rat model. METHODS: Anesthetized
      open-chest male Wistar rats were subjected to 45 minutes of left coronary artery
      occlusion and 2 hours of reperfusion. Opioid agonists were infused 15 minutes
      prior to coronary artery occlusion. Two control groups and 15 opioid-treated
      groups were studied. Controls were infused with either saline alone (n = 16) or
      dimethyl sulfoxide plus hydroxypropyl-beta-cyclodextrin in saline (n = 19). The
      MU-selective agonist DAMGO was infused at either 150 nmol/kg (n = 15) or 1500
      nmol/kg (n = 14), and dermorphin-H was infused at 150 nmol/kg (n = 14). The
      delta1 -selective agonist d-Pen2(,)5 enkephalin (DPDPE) was infused at 150
      nmol/kg (n = 16) or 1500 nmol/kg (n = 14). The delta2 -selective agonists
      deltorphin II (n = 16), deltorphin-D(variant) (n = 15), and deltorphin-E (n = 14)
      were infused at 150 nmol/kg. The selective kappa1 opioid agonist U-50488 was
      infused at 240 nmol/kg (n = 14), 1500 nmol/kg (n = 14), and 2,400 nmol/kg (n =
      14). The selective kappa2 opioid agonist GR-89696 was infused at 150 nmol/kg (n =
      14) and 1500 nmol/kg (n = 15). Orphinan FQ (nociceptin), also referred to as OR
      like 1 (ORL1), was infused at 220 nmol/kg (n = 15) and 1500 nmol/kg (n = 15). The
      infarct size/area at risk (IS/AAR) ratio was determined after reperfusion by
      negative staining with patent blue violet dye. Hemodynamic parameters including
      heart rate, mean arterial blood pressure (MAP), and rate pressure product (RPP)
      were determined. RESULTS: Pretreatment with the delta2 OR agonist deltorphin II
      (150 nmol/kg) significantly reduced the IS/AAR ratio, while deltorphin-D(variant)
      and deltorphin-E did not exhibit an infarct-sparing effect at that treatment
      dose. Activation of delta1 OR by DPDPE, kappa1 OR by U-50488, kappa2 OR by GR
      89696, MU OR by DAMGO, dermorphin-H, and nociceptin had no effect on the IS/AAR
      ratio. U-50488 at 2,400 nmol/L induced a bradycardic effect. All other opioids
      had no effect on hemodynamic parameters at the doses tested. CONCLUSIONS:
      Peripheral delta2 OR activation by deltorphin II induces infarct size reduction
      in this animal model. Agonists of MU, delta1, kappa1, kappa2, and nociceptin
      receptors at the doses tested did not induce cardiac tolerance to
      ischemia/reperfusion injury in vivo.

PMID- 21175525
TI  - Palliative care needs of seriously ill, older adults presenting to the emergency
      department.
AB  - OBJECTIVES: The objective was to identify the palliative care needs of seriously
      ill, older adults in the emergency department (ED). METHODS: The authors
      conducted a cross-sectional structured survey. A convenience sample of 50
      functionally impaired adults 65 years or older with coexisting cancer, congestive
      heart failure, end-stage liver or renal disease, stroke, oxygen-dependent
      pulmonary disease, or dementia was recruited from an urban academic tertiary care
      ED. Face-to-face interviews were conducted using the Needs Near the End-of-Life
      Screening Tool (NEST), McGill Quality of Life Index (MQOL), and Edmonton Symptom
      Assessment Survey (ESAS) to assess 1) range and severity of symptoms, 2) goals of
      care, 3) psychological well-being, 4) health care utilization, 5) spirituality,
      6) social connectedness, 7) financial burden, 8) the patient-clinician
      relationship, and 9) overall quality of life (QOL). RESULTS: Mean (+/-SD) age was
      74.3 (+/-6.5) years and cancer was the most common diagnosis. Mean (+/-SD) QOL on
      the MQOL was 3.6 (+/-2.9). Over half of the patients exceeded intratest severity
      of-needs cutoffs in four categories of the NEST: physical symptoms (47/50, 94%),
      finances (36/50, 72%), mental health (31/50, 62%), and access to care (29/50,
      58%). The majority of patients reported moderate to severe fatigue, pain,
      dyspnea, and depression on the ESAS. CONCLUSIONS: Seriously ill, older adults in
      an urban ED have substantial palliative care needs. Future work should focus on
      the role of emergency medicine and the new specialty of palliative care in
      addressing these needs.

PMID- 21175530
TI  - Calling all presenters.

PMID- 21175531
TI  - Lessons from families and communities about interpersonal violence,
      victimization, and seeking help.
AB  - Despite significant incidence and physical and mental health consequences, most
      college-age women do not tell anyone about experiences of interpersonal violence.
      Limited research explores the sociocultural context of seeking help related to
      violence in young women. The overall purpose of this research was to understand
      socially and culturally relevant factors associated with violence help seeking in
      college women. Eight focus groups were held with 64 participants. Narrative
      analysis was the primary method of analysis. Four qualitative categories emerged
      from the data: "Learning from one's mother"; "We're strong women; we fight"; "We
      didn't talk about it"; and "Where I'm from." Findings suggest that help seeking
      is influenced by the messages from and experiences of mothers and extended family
      members. An understanding of familial and cultural determinants of help seeking
      is essential for relevant and effective prevention efforts.

PMID- 21175532
TI  - Comparison by crime type of juvenile delinquents on pornography exposure: the
      absence of relationships between exposure to pornography and sexual offense
      characteristics.
AB  - Previous literature on pornography indicates that pornography use for men at risk
      for aggression may result in sexually aggressive behavior, but very little
      research has been reported on juvenile sexual abusers' exposure to pornography.
      The current study compared pornography exposure between male adolescent sexual
      abusers (n=283) and male nonsexually offending delinquent youth (n=170). Sexual
      abusers reported more pre- and post-10 (years of age) exposure to pornography
      than nonsexual abusers. Yet, for the sexual abusers, exposure is not correlated
      to the age at which the abusers started abusing, to their reported number of
      victims, or to sexual offense severity. The pre-10 exposure subscale was not
      related to the number of children the group sexually abused, and the forceful
      exposure subscale was not correlated with either arousal to rape or degree of
      force used by the youth. Finally, exposure was significantly correlated with all
      of the nonsexual crime scores in the study. Implications for forensic nursing are
      discussed.

PMID- 21175533
TI  - Chronic traumatic encephalopathy in a professional American wrestler.
AB  - We present in this case report the tissue substrates and forensic evidence for
      chronic traumatic encephalopathy (CTE) in a professional American wrestler with
      Apolipoprotein E (apoE) genotyping. Professional wrestling is a contact-sport,
      with an integral risk for players to sustain repeated concussions over their
      careers. This case provides the first autopsy evidence of neuropathological
      abnormalities that accompany CTE in professional American wrestlers. A complete
      autopsy was performed on a 40-year-old Caucasian male, after he died unexpectedly
      by suicidal hanging after he had killed his wife and son. The brain showed no
      atrophy and no recent or remote contusions or necrosis. There was a mild to
      moderate neocortical neuronal dropout without any amyloid plaques. There were
      diffuse, sparse to frequent tau-immunoreactive Neurofibrillary Tangles and
      Neuropil Threads in the neocortex, subcortical ganglia, and brainstem nuclei
      including the substantia nigra consistent with CTE. The apoE genotype was
      determined to be E3/E3. Other autopsy findings included cardiomegaly, left
      ventricular hypertrophy, and bilateral atrioventricular dilatation; toxicologic
      analyses showed alprazolam and hydrocodone in the blood, and evidence of
      exogenous testosterone in the urine. Longitudinal studies of professional contact
      sport athletes are needed to identify the differentiating characteristics of
      athletes who develop CTE and devise strategies for intervention.

PMID- 21175534
TI  - Oral health related quality of life among imprisoned Dutch forensic psychiatric
      patients.
AB  - Because dental health and oral pathology may affect forensic psychiatric
      patients' well being, it is important to be able to assess oral health related
      quality of life (OH-QoL) in these patients. Two studies were conducted among
      Dutch forensic psychiatric male patients to assess the psychometric properties
      and some potential predictors of the Oral Health Impact Profile-14 (OHIP-14) as a
      measure of OH-QoL. Study 1 involved 40 patients who completed the OHIP-14 before
      receiving professional dental care and were retested 3 months later. The internal
      consistency was good, the test-retest correlations were fair, and over the 3
      months follow-up no significant changes in OH-QoL were observed. Study 2
      consisted of 39 patients who completed an improved version of the original OHIP
      14, as well as measures to validate of the OHIP. Dental anxiety and unhealthy
      dentition jointly explained 26.7% of the variance in OH-QoL, and the better
      patients performed their oral hygiene behavior, the better their OH-QoL. It is
      concluded that the Dutch OHIP-14 is a useful instrument, and that nurses,
      especially in forensic nursing, should pay particularly attention to dental
      anxiety when encouraging patients to visit OH professionals and to perform
      adequate oral hygiene self-care.

PMID- 21175535
TI  - A source of healthcare disparity: race, skin color, and injuries after rape among
      adolescents and young adults.
AB  - Differences in anogenital injury resulting from rape may occur because of racial
      or skin color differences in adult women. It is critical to determine if these
      differences also are associated with differences in injury prevalence and
      frequency in adolescents and young adults. In a retrospective review of medical
      records, we examined whether Black adolescent/young adult females had different
      anogenital injuries as compared to White females following rape. Next, we
      examined whether skin color differences explained a significant amount of the
      racial difference in injuries. We reviewed charts of 234 female victims of rape
      ages 14 to 29. Overall injury prevalence was 62.8%. Race was significantly
      associated with frequency of injuries in several anatomical locations, with White
      victims having a higher frequency of injuries than Black victims. Skin color was
      significantly associated with injury frequency in many anatomical locations, with
      victims with light skin sustaining more injuries than victims with dark skin.
      Even when skin color was included in the relationship, race remained a
      statistically significant factor, suggesting that the relationship between race
      and injuries may be more complicated than merely a skin color difference that has
      been mislabeled a racial difference.

PMID- 21175536
TI  - The forensic nurse and violence prevention and response in public health.

PMID- 21175537
TI  - Abusive head trauma.

PMID- 21175540
TI  - 30(th) Annual Meeting of the Japanese Society for Apheresis.

PMID- 21175541
TI  - Multicenter study of plasma diafiltration in patients with acute liver failure.
AB  - Plasma diafiltration (PDF) is a blood purification therapy in which simple plasma
      exchange (PE) is performed using a selective membrane plasma separator while the
      dialysate flows outside the hollow fibers. A prospective, multicenter study was
      undertaken to evaluate the changes in bilirubin, IL-18, and cystatin C, as well
      as the 28-day and 90-day survival rates, with the use of PDF according to the
      level of severity as measured by the Model for End-Stage Liver Disease (MELD)
      score. Twenty-one patients with liver failure were studied: 10 patients had
      fulminant hepatitis and PDF therapies were performed 28 times; 11 had acute liver
      failure with the therapy performed 96 times. Levels of total bilirubin, IL-18,
      and cystatin C decreased significantly after treatment. The 28-day survival rate
      was 70.0% and that at 90 days was 16.7%. According to the severity of the MELD
      score, each of the results compared well with the use of Molecular Adsorbent
      Recirculating System or Prometheus therapy. In conclusion, PDF appears to be one
      of the most useful blood purification therapies for use in cases of acute liver
      failure in terms of medical economics and the removal of water-soluble and
      albumin-bound toxins.

PMID- 21175543
TI  - Platelet function, activation and apoptosis during and after apheresis.
AB  - Platelets are known to undergo shape change, activation, release reaction and
      apoptosis/necrosis during processing and storage. Apheresis may have a
      deleterious impact on platelet achievability and functional integrity. Platelet
      concentrates from 50 male volunteers obtained by COBE spectra were screened for
      platelet activation (CD62 and CD154) and apoptosis (phosphatidylserine detected
      by Annexin V). Donor samples before separation, during apheresis and at the third
      day of storage were used as baseline donor samples. Platelet aggregation to
      adenosine diphosphate (ADP) and collagen was performed. There was a statistically
      significant increase in the expression of activation markers in two different
      samples (during separation samples and third day samples). Although the increase
      in Annexin V expression was not so observable, it showed a significant increase
      also. There was marked decline in the platelet aggregation. The correlations
      between the values of CD62, CD154 and Annexin V were detected in baseline samples
      and increased during separation and at the third day of platelets storage.
      Correlation between values of platelet aggregation to collagen and Annexin V was
      relevant only in the baseline samples. No other correlations were encountered
      between platelet aggregation and markers of activation and apoptosis during
      apheresis and storage. Initial platelet activation induced by apheresis may have
      an impact on phosphatidylserine expression with no impact on aggregation function
      of platelets during storage.

PMID- 21175542
TI  - Evaluation of blood purification and bortezomib plus dexamethasone therapy for
      the treatment of acute renal failure due to myeloma cast nephropathy.
AB  - Aggressive removal of circulating free light chains (FLC) by blood purification
      accompanied by chemotherapy is a promising approach for the treatment of acute
      renal failure due to myeloma cast nephropathy. Plasma exchange has been performed
      to remove serum FLC; in order to examine an alternative strategy we performed
      hemodiafiltration using protein-leaking dialyzers for the treatment of dialysis
      dependent acute renal failure due to myeloma cast nephropathy. In the first case
      with kappa-light chain cast nephropathy, the pre-treatment serum creatinine was
      9.65 mg/dL, and the serum kappa-FLC was 27100 mg/L. Plasma exchange or
      hemodiafiltration was performed from Monday to Friday during the first several
      weeks. Chemotherapy was started with high-dose dexamethasone and then switched to
      bortezomib plus dexamethasone. The mean removal rates of kappa-FLC were 45.8%
      (one plasma volume) and 66.9% (one-and-a-half plasma volumes) by plasma exchange.
      The removal rates of kappa-FLC by hemodiafiltration (66.9%, FB210UHbeta; 71.6%,
      PES210Dalpha; 75.2%, FXS220) were comparable to those by plasma exchange. In the
      second case with lambda-light chain cast nephropathy, the pre-treatment serum
      creatinine was 4.14 mg/dL, and the serum lambda-FLC was 4140 mg/L. The mean
      removal rates of lambda-FLC were 60.2% (FXS140) and 64.2% (FB210UHbeta) by
      hemodiafiltration. Both cases became dialysis-independent. The combination of an
      intense blood purification regimen and bortezomib plus dexamethasone therapy
      appears to be an efficient approach to renal recovery. Hemodiafiltration using
      protein-leaking dialyzers could become an alternative to plasma exchange as a
      method of removing FLC.

PMID- 21175544
TI  - The redox state of albumin and serious cardiovascular incidence in hemodialysis
      patients.
AB  - Human serum albumin is composed of human mercaptoalbumin (HMA) with cysteine
      residues having reducing powers and oxidized human non-mercaptoalbumin. The aim
      of this study is to clarify whether such redox state of albumin (HSA-redox)
      influences the incidence of cardiovascular disease (CVD) in chronic kidney
      disease patients on regular hemodialysis (HD). We measured HSA-redox using high
      performance liquid chromatography in 86 anuric HD patients. The association
      between HSA-redox and incidental CVD events was evaluated. Twenty patients
      experienced symptomatic CVD events (16 patients died) at the 2-year follow-up.
      The fraction of HMA (f(HMA)) showed a significantly lower value in patients with
      CVD than that without CVD, in both pre-HD (36.5 +/- 5.8% and 44.6 +/- 9.8%,
      respectively) and post-HD (57.2 +/- 6.2% and 67.2 +/- 7.4%, respectively). The
      adjusted odds ratio (OR) for the incidental CVD event in patients with pre-HD
      f(HMA) < 40% was 5.0 (95% CI; 1.2 to 21.3), and that in patients with post-HD
      f(HMA) < 60% was 20.6 (3.2 to 134.7). Likewise, the adjusted OR for the CVD death
      in patients with pre-HD f(HMA) < 40% was 2.5 (0.6 to 12.5), and that in patients
      with post-HD f(HMA) < 60% was 25.6 (2.5 to 262.8). In conclusion, HSA-redox is
      closely related to serious CVD incidence and mortality among HD patients.

PMID- 21175545
TI  - Beraprost sodium, an orally active prostaglandin I(2) analog, improves renal
      anemia in hemodialysis patients with peripheral arterial disease.
AB  - Beraprost sodium (BPS) is a stable, orally active prostaglandin I(2) (PGI(2) )
      analog with antiplatelet and vasodilating properties. It has been reported that
      PGI(2) has pleiotropic effects that are anti-inflammatory and anti-atherogenic.
      In this study, we aim to determine the relationship between PGI(2) and renal
      anemia. We conducted a prospective randomized trial including 20 hemodialysis
      patients. Ten patients were assigned to be treated with 120 ug/day of BPS and the
      other patients were assigned to a control group. After six months, the titer of
      hemoglobin had significantly increased in the BPS group compared to the baseline
      (11.1 +/- 0.3 g/dL vs. 10.3 +/- 1.4 g/dL, respectively), and there was a
      significant difference between the BPS group and the control group. The level of
      ferritin was lower in the BPS group compared to the control group, but the
      average dose of erythropoietin did not significantly change. These findings
      suggest that BPS may improve renal anemia in hemodialysis patients.

PMID- 21175546
TI  - Low-grade endotoxemia contributes to chronic inflammation in hemodialysis
      patients: examination with a novel lipopolysaccharide detection method.
AB  - Chronic inflammation has recently been proposed to play a major role in the
      development of cardiovascular disease and mortality among advanced chronic kidney
      disease (CKD) patients; however, why advanced CKD promotes chronic inflammation
      is still unclear. We hypothesized that a very low level of plasma endotoxin
      (lipopolysaccharide [LPS]) contributes to chronic inflammation in advanced CKD
      patients. We measured the plasma LPS levels using a novel LPS detection method
      (ESP method, a method for endotoxin detection using laser scattering photometry)
      concurrently with serum C-reactive protein (CRP) levels and various blood tests
      in 17 stable hemodialysis (HD) patients. As a result, the median LPS levels
      measured by the ESP method was 0.23 pg/mL (range, 0.01-3.89) (inflow, start of
      HD), 0.22 pg/mL (<0.01-9.97) (outflow, start of HD), 0.37 pg/mL (<0.01-7.42)
      (inflow, end of HD), and 1.07 pg/mL (<0.01-10.66) (dialysate), respectively;
      statistically significant differences were not detected between them. The
      predialysis median CRP level was 0.19 mg/dL (0.04-3.02). The logarithm of plasma
      LPS independently correlated with serum CRP (R = 0.595, P = 0.0103). In multiple
      (forward stepwise) regression analysis, in which CRP was determined to be the
      criterion variable, LPS (log), albumin, and the white blood cell count were
      adopted as independent explanatory variables (R = 0.401, -0.397 and 0.387,
      respectively). In conclusion, the present study revealed a significant
      relationship between LPS and CRP using the novel ESP method, and suggested that
      very low-grade endotoxemia is contributing to systemic inflammation in HD
      patients.

PMID- 21175547
TI  - Amanita ibotengutake intoxication treated with plasma exchange.

PMID- 21175548
TI  - Low-density lipoprotein apheresis using double filtration plasmapheresis: 27
      month use in a child with homozygous familial hypercholesterolemia.

PMID- 21175550
TI  - Is bone marrow another target of diabetic complications?

PMID- 21175551
TI  - Relationship between cytomegalovirus  infection and procoagulant changes in 
      human immunodeficiency virus-infected  patients.
AB  - Cytomegalovirus is associated with hypercoagulability, and is reported to
      increase the risk of venous thrombosis in human immunodeficiency virus (HIV)
      infected patients. Progression to AIDS, however, is also associated with
      hypercoagulability and venous thrombosis, and may result in more comorbidities,
      such as reactivation of cytomegalovirus. It is therefore unknown whether active
      cytomegalovirus in HIV infection results in a procoagulant state or whether
      hypercoagulability is the result of HIV infection itself. In this cross-sectional
      study of 104 consecutive HIV-infected patients, active cytomegalovirus infection
      was associated with hypercoagulability independently of stage of HIV disease.
      This finding may deserve attention in preventative recommendations for use of
      thromboprophylaxis in HIV-infected patients.

PMID- 21175552
TI  - Aberrant ventral striatal responses during incentive processing in unmedicated
      patients with obsessive-compulsive disorder.
AB  - OBJECTIVE: Obsessive-compulsive disorder (OCD) is characterized by the
      dysfunction of control and reward mechanisms. However, only few neuroimaging
      studies of OCD have examined the reward processing. We examined the neural
      responses during incentive processing in OCD. METHOD:   Twenty unmedicated
      patients with OCD and 20 age-, sex-, and IQ-matched healthy controls underwent
      functional magnetic resonance imaging while performing a modified monetary
      incentive delay task. RESULTS: Compared with controls, patients with OCD showed
      increased ventral striatal activation in the no-loss minus loss outcome contrast
      and a significant positive correlation between the ventral striatal activation
      and compulsion symptom severity. In addition, patients with OCD showed increased
      activations in the frontostriatal regions in the gain minus no-gain outcomes
      contrast. During loss anticipation, patients with OCD showed less activations in
      the lateral prefrontal and inferior parietal cortices. However, during gain
      anticipation, patients with OCD and healthy controls did not differ in the
      ventral striatal activation. CONCLUSION: These findings provide neural evidence
      for altered incentive processing in unmedicated patients with OCD, suggesting an
      elevated sensitivity to negatively affect stimuli as well as dysfunction of the
      ventral striatum.

PMID- 21175553
TI  - Bayesian semiparametric intensity estimation for inhomogeneous spatial point
      processes.
AB  - In this work we propose a fully Bayesian semiparametric method to estimate the
      intensity of an inhomogeneous spatial point process. The basic idea is to first
      convert intensity estimation into a Poisson regression setting via binning data
      points on a regular grid, and then model the log intensity semiparametrically
      using an adaptive version of Gaussian Markov random fields to smooth the
      corresponding counts. The inference is carried by an efficient Markov chain Monte
      Carlo simulation algorithm. Compared to existing methods for intensity
      estimation, for example, parametric modeling and kernel smoothing, the proposed
      estimator not only provides inference regarding the dependence of the intensity
      function on possible covariates, but also uses information from the data to
      adaptively determine the amount of smoothing at the local level. The
      effectiveness of using our method is demonstrated through simulation studies and
      an application to a rainforest dataset.

PMID- 21175554
TI  - Semiparametric bayes' proportional odds models for current status data with
      underreporting.
AB  - Current status data are a type of interval-censored event time data in which all
      the individuals are either left or right censored. For example, our motivation is
      drawn from a cross-sectional study, which measured whether or not fibroid onset
      had occurred by the age of an ultrasound exam for each woman. We propose a
      semiparametric Bayesian proportional odds model in which the baseline event time
      distribution is estimated nonparametrically by using adaptive monotone splines in
      a logistic regression model and the potential risk factors are included in the
      parametric part of the mean structure. The proposed approach has the advantage of
      being straightforward to implement using a simple and efficient Gibbs sampler,
      whereas alternative semiparametric Bayes' event time models encounter problems
      for current status data. The model is generalized to allow systematic
      underreporting in a subset of the data, and the methods are applied to an
      epidemiologic study of uterine fibroids.

PMID- 21175555
TI  - Prediction-based structured variable selection through the receiver operating
      characteristic curves.
AB  - In many clinical settings, a commonly encountered problem is to assess accuracy
      of a screening test for early detection of a disease. In these applications,
      predictive performance of the test is of interest. Variable selection may be
      useful in designing a medical test. An example is a research study conducted to
      design a new screening test by selecting variables from an existing screener with
      a hierarchical structure among variables: there are several root questions
      followed by their stem questions. The stem questions will only be asked after a
      subject has answered the root question. It is therefore unreasonable to select a
      model that only contains stem variables but not its root variable. In this work,
      we propose methods to perform variable selection with structured variables when
      predictive accuracy of a diagnostic test is the main concern of the analysis. We
      take a linear combination of individual variables to form a combined test. We
      then maximize a direct summary measure of the predictive performance of the test,
      the area under a receiver operating characteristic curve (AUC of an ROC), subject
      to a penalty function to control for overfitting. Since maximizing empirical AUC
      of the ROC of a combined test is a complicated nonconvex problem (Pepe, Cai, and
      Longton, 2006, Biometrics62, 221-229), we explore the connection between the
      empirical AUC and a support vector machine (SVM). We cast the problem of
      maximizing predictive performance of a combined test as a penalized SVM problem
      and apply a reparametrization to impose the hierarchical structure among
      variables. We also describe a penalized logistic regression variable selection
      procedure for structured variables and compare it with the ROC-based approaches.
      We use simulation studies based on real data to examine performance of the
      proposed methods. Finally we apply developed methods to design a structured
      screener to be used in primary care clinics to refer potentially psychotic
      patients for further specialty diagnostics and treatment.

PMID- 21175556
TI  - Exploring spatial and temporal variations of cadmium concentrations in pacific
      oysters from british columbia.
AB  - Oysters from the Pacific Northwest coast of British Columbia, Canada, contain
      high levels of cadmium, in some cases exceeding some international food safety
      guidelines. A primary goal of this article is the investigation of the spatial
      and temporal variation in cadmium concentrations for oysters sampled from coastal
      British Columbia. Such information is important so that recommendations can be
      made as to where and when oysters can be cultured such that accumulation of
      cadmium within these oysters is minimized. Some modern statistical methods are
      applied to achieve this goal, including monotone spline smoothing, functional
      principal component analysis, and semi-parametric additive modeling. Oyster
      growth rates are estimated as the first derivatives of the monotone smoothing
      growth curves. Some important patterns in cadmium accumulation by oysters are
      observed. For example, most inland regions tend to have a higher level of cadmium
      concentration than most coastal regions, so more caution needs to be taken for
      shellfish aquaculture practices occurring in the inland regions. The semi
      parametric additive modeling shows that oyster cadmium concentration decreases
      with oyster length, and oysters sampled at 7 m have higher average cadmium
      concentration than those sampled at 1 m.

PMID- 21175557
TI  - A new u-statistic with superior design sensitivity in matched observational
      studies.
AB  - In an observational or nonrandomized study of treatment effects, a sensitivity
      analysis indicates the magnitude of bias from unmeasured covariates that would
      need to be present to alter the conclusions of a naive analysis that presumes
      adjustments for observed covariates suffice to remove all bias. The power of
      sensitivity analysis is the probability that it will reject a false hypothesis
      about treatment effects allowing for a departure from random assignment of a
      specified magnitude; in particular, if this specified magnitude is "no departure"
      then this is the same as the power of a randomization test in a randomized
      experiment. A new family of u-statistics is proposed that includes Wilcoxon's
      signed rank statistic but also includes other statistics with substantially
      higher power when a sensitivity analysis is performed in an observational study.
      Wilcoxon's statistic has high power to detect small effects in large randomized
      experiments-that is, it often has good Pitman efficiency-but small effects are
      invariably sensitive to small unobserved biases. Members of this family of u
      statistics that emphasize medium to large effects can have substantially higher
      power in a sensitivity analysis. For example, in one situation with 250 pair
      differences that are Normal with expectation 1/2 and variance 1, the power of a
      sensitivity analysis that uses Wilcoxon's statistic is 0.08 while the power of
      another member of the family of u-statistics is 0.66. The topic is examined by
      performing a sensitivity analysis in three observational studies, using an
      asymptotic measure called the design sensitivity, and by simulating power in
      finite samples. The three examples are drawn from epidemiology, clinical
      medicine, and genetic toxicology.

PMID- 21175559
TI  - STROBE and reporting observational studies in dermatology.

PMID- 21175560
TI  - Patch test technique.

PMID- 21175561
TI  - Role of apoptosis and melanocytorrhagy: a comparative study of melanocyte
      adhesion in stable and unstable vitiligo.
AB  - BACKGROUND: Apoptosis and melanocytorrhagy have been proposed as mechanisms of
      melanocyte disappearance although there are few controlled studies. OBJECTIVES:
      We undertook this project to study melanocyte morphology and adhesion defects in
      patients with stable and unstable disease in controls. METHODS: In this
      comparative study we included seven patients with stable disease and seven
      patients with unstable vitiligo. We cultured perilesional skin melanocytes from
      these patients with stable and unstable vitiligo and studied for morphological
      changes, adhesion to collagen type IV and caspase 3 expression. Melanocytes were
      also treated with okadaic acid and annexin V expression was then checked and
      compared between controls and patients with stable and unstable vitiligo.
      RESULTS: Perilesional skin melanocytes from patients with unstable vitiligo
      revealed some significant morphological changes. Melanocytes from unstable
      vitiligo showed significantly low adhesion to collagen type IV compared with
      control and stable vitiligo melanocytes. Our results showed that caspase 3 and
      annexin V staining was significantly greater in melanocytes cultured from
      unstable vitiligo compared with the control. CONCLUSIONS: In this study we
      demonstrated that melanocytes in the patients with unstable vitiligo were in
      their detachment phase, which ultimately leads to apoptosis of these cells,
      whereas melanocytes cultured from controls and from patients with stable vitiligo
      were morphologically normal without any adhesion defects. These morphological and
      adhesion findings support the theory of melanocytorrhagy as the primary defect
      underlying melanocyte loss in unstable vitiligo.

PMID- 21175562
TI  - Maggot chymotrypsin I from Lucilia sericata is resistant to endogenous wound
      protease inhibitors.
AB  - BACKGROUND: A chymotrypsin found in the secretions of Lucilia sericata and
      manufactured as a recombinant enzyme degrades chronic wound eschar ex vivo.
      OBJECTIVES: To characterize the inhibition profile of the L. sericata recombinant
      chymotrypsin I. METHODS: Activity of recombinant chymotrypsin I and its
      sensitivity to endogenous inhibitors were determined enzymatically using the
      fluorogenic substrate succinyl-alanyl-alanyl-prolyl-phenylalanyl-aminomethyl
      coumarin. RESULTS: We report the presence of high concentrations of two
      endogenous inhibitors, alpha1-antichymotrypsin and alpha1-antitrypsin, in wound
      eschar and a trace of a third, alpha2-macroglobulin, with the potential to
      inhibit this debridement process. However, the addition of a soluble and
      inhibitor-containing extract of chronic wound eschar to chymotrypsin I did not
      affect activity of the enzyme, neither did the addition of purified native alpha1
      antichymotrypsin or alpha1-antitrypsin, although chymotrypsin I was inhibited by
      alpha2-macroglobulin. Conversely, the mammalian equivalent, alpha-chymotrypsin,
      was inhibited by the purified native alpha1-antichymotrypsin, alpha1-antitrypsin
      and alpha2-macroglobulin and by the soluble extract of wound eschar. CONCLUSIONS:
      The data suggest that the maggot-derived chymotrypsin I is biochemically distinct
      from human alpha-chymotrypsin and the lack of inhibition by wound eschar suggests
      a means by which chymotrypsin I activity survives within the wound to contribute
      towards debridement during maggot biotherapy.

PMID- 21175563
TI  - Seven-point checklist of dermoscopy revisited.
AB  - BACKGROUND: Most dermoscopic algorithms to diagnose melanoma were established
      more than 10 years ago and have been tested primarily on clear-cut melanomas and
      excised melanocytic naevi. OBJECTIVES: To assess the diagnostic performance of
      pattern analysis and seven-point checklist on lesions that reflect the current
      clinical setting, compared with a revised seven-point checklist with a lower
      threshold for excision. METHODS: Eight experienced dermatologists viewed
      dermoscopic images of 100 excised melanomas, 100 excised naevi and 100 monitored
      naevi. Each lesion was evaluated by pattern analysis and scored as naevus,
      melanoma or lesion to be excised. Images were then evaluated using the seven
      point criteria, with both standard and revised thresholds for excision. RESULTS:
      Pooled data using the pattern analysis algorithm showed that 82% of melanomas and
      87.5% of monitored naevi were correctly scored as lesion to be excised and benign
      naevus, respectively. Using the standard and revised thresholds for the seven
      point checklist, excision was recommended for 77.9% and 87.8% of the lesions in
      the melanoma set, respectively. The standard threshold produced 'no excision'
      recommendations for 85.6% of the monitored naevi, compared with 74.5% using the
      revised threshold. Pattern analysis, standard seven-point and revised seven-point
      algorithms resulted in recommendations of 'excision' for 63.6%, 60.3% and 72.0%
      of the excised naevi, respectively. CONCLUSIONS: The diagnostic approach to naevi
      and melanoma should be adapted to the current clinical setting, in which patients
      may present with early-stage melanomas and multiple atypical naevi. To increase
      sensitivity, a revised seven-point checklist with a lower threshold for excision
      should be used.

PMID- 21175564
TI  - Fumarates vs. methotrexate in moderate to severe chronic plaque psoriasis: a
      multicentre prospective randomized controlled clinical trial.
AB  - BACKGROUND: Methotrexate and fumarates are effective systemic therapies for
      moderate to severe psoriasis according to the European S3 guidelines. OBJECTIVES:
      We conducted a randomized controlled trial comparing the effectiveness and the
      adverse events of methotrexate and fumarates. METHODS: Sixty patients with
      moderate to severe psoriasis vulgaris were randomly assigned to treatment for 16
      weeks with either methotrexate (30 patients; 15 mg per week) or fumarates (30
      patients; 30 mg, followed by 120 mg according to a standard progressive dosage
      regimen) and were followed up for 4 weeks. The primary endpoint with respect to
      the efficacy was the difference in mean change from baseline in Psoriasis Area
      and Severity Index (PASI) after 12 weeks of treatment. The study was powered to
      detect a difference of five points. Analyses were by intention to treat. RESULTS:
      Six patients were excluded because five were not eligible and one withdrew
      consent. Two patients in the methotrexate group and one in the fumarate group
      dropped out during the 12 weeks of treatment because of nonappearance at the
      outpatient clinic. In total, 25 patients in the methotrexate group and 26 in the
      fumarate group were evaluated in the primary analysis. After 12 weeks of
      treatment, the mean +/- SD PASI decreased from 14.5 +/- 3.0 at baseline to 6.7 +/
      4.5 in the 25 patients treated with methotrexate, whereas it decreased from 18.1
      +/- 7.0 to 10.5 +/- 6.7 in the 26 patients treated with fumarates. After
      adjustment for baseline values, the absolute difference (fumarates minus
      methotrexate) in the mean values at 12 weeks was 1.4 (95% confidence interval 
      2.0 to 4.7; P = 0.417). CONCLUSIONS: In this randomized trial methotrexate and
      fumarates were found to be equally effective in the treatment of patients with
      moderate to severe psoriasis. No serious or irreversible adverse events were
      observed in any of the patients.

PMID- 21175565
TI  - Syndrome of inappropriate antidiuretic hormone secretion associated with plasma
      cell myeloma.

PMID- 21175566
TI  - Intracranial mass in a patient with thalassaemia major.

PMID- 21175567
TI  - Anti-angiogenic effects of two cystine-knot miniproteins from tomato fruit.
AB  - BACKGROUND AND PURPOSE: Cystine-knot miniproteins are characterized by a similar
      molecular structure. Some cystine-knot miniproteins display therapeutically
      useful biological activities, as antithrombotic agents or tumour growth
      inhibitors. A critical event in the progression of tumours is the formation of
      new blood vessels. The aim of this work was to test two tomato cystine-knot
      miniproteins for their effects on endothelial cell proliferation and angiogenesis
      in vitro. EXPERIMENTAL APPROACH: Two tomato cystine-knot miniproteins (TCMPs)
      were expressed and purified either as recombinant or as native proteins from
      tomato fruits. The Matrigel assay was used to investigate the effects of TCMPs on
      in vitro angiogenesis. Viability and proliferation of endothelial cells were
      tested. Extracellular signal-regulated kinase (ERK)1/2 phosphorylation was
      assayed in either HUVEC or A431 epidermal growth factor receptor (EGFR)
      overexpressing cells treated with TCMPs. EGFR phosphorylation was tested in A431
      cells. KEY RESULTS: Both recombinant and native TCMPs inhibited in vitro
      angiogenesis of HUVEC cells at concentrations of 15-100 nM. The anti-angiogenic
      effect of TCMPs was associated with the inhibition of ERK phosphorylation. The
      two miniproteins did not alter the viability and proliferation of the endothelial
      cells. CONCLUSIONS AND IMPLICATIONS: The anti-angiogenetic properties of TCMPs
      are of potential pharmacological interest because they are common and natural
      components of the human diet, they possess low toxicity, they are active at
      submicromolar concentrations, they share a common molecular structure that can be
      used as a molecular platform for the design of molecules with enhanced biological
      activity.

PMID- 21175568
TI  - The C-terminal fragment of parathyroid hormone-related peptide promotes bone
      formation in diabetic mice with low-turnover osteopaenia.
AB  - BACKGROUND AND PURPOSE: Current data suggest that parathyroid hormone (PTH)
      related peptide (PTHrP) domains other than the N-terminal PTH-like domain
      contribute to its role as an endogenous bone anabolic factor. PTHrP-107-139
      inhibits bone resorption, a fact which has precluded an unequivocal demonstration
      of its possible anabolic action in vivo. We thus sought to characterize the
      osteogenic effects of this peptide using a mouse model of diabetic low-turnover
      osteopaenia. EXPERIMENTAL APPROACH: PTHrP-107-139 was administered to
      streptozotocin-induced diabetic mice, with or without bone marrow ablation, for
      13 days. Osteopaenia was confirmed by dual-energy X-ray absorptiometry and
      microcomputed tomography analysis. Histological analysis was performed on
      paraffin-embedded bone tissue sections by haematoxylin/eosin and Masson's
      staining, and tartrate-resistent acid phosphatase immunohistochemistry. Mouse
      bone marrow stromal cells and osteoblastic MC3T3-E1 cells were cultured in normal
      and/or high glucose (HG) medium. Osteogenic and adipogenic markers were assessed
      by real-time PCR, and PTHrP and the PTH(1) receptor protein expression by Western
      blot analysis. KEY RESULTS: PTHrP-107-139 reversed the alterations in bone
      structure and osteoblast function, and also promoted bone healing after marrow
      ablation without affecting the number of osteoclast-like cells in diabetic mice.
      This peptide also reversed the high-glucose-induced changes in osteogenic
      differentiation in both bone marrow stromal cells and the more differentiated
      MC3T3-E1 cells. CONCLUSIONS AND IMPLICATIONS: These findings demonstrate that
      PTHrP-107-139 promotes bone formation in diabetic mice. This mouse model and in
      vitro cell cultures allowed us to identify various anabolic effects of this
      peptide in this scenario.

PMID- 21175569
TI  - Ligand-induced internalization of the orexin OX(1) and cannabinoid CB(1)
      receptors assessed via N-terminal SNAP and CLIP-tagging.
AB  - BACKGROUND AND PURPOSE: Many G protein-coupled receptors internalize following
      agonist binding. The studies were designed to identify novel means to effectively
      quantify this process using the orexin OX(1) receptor and the cannabinoid CB(1)
      receptor as exemplars. EXPERIMENTAL APPROACH: The human OX(1) and CB(1) receptors
      were modified to incorporate both epitope tags and variants (SNAP and CLIP) of
      the enzyme O(6)-alkylguanine-DNA-alkyltransferase within their extracellular, N
      terminal domain. Cells able to regulate expression of differing amounts of these
      constructs upon addition of an antibiotic were developed and analysed. KEY
      RESULTS: Cell surface forms of each receptor construct were detected by both
      antibody recognition of the epitope tags and covalent binding of fluorophores to
      the O(6)-alkylguanine-DNA-alkyltransferase variants. Receptor internalization in
      response to agonists but not antagonists could be monitored by each approach but
      sensitivity was up to six- to 10-fold greater than other approaches when
      employing a novel, time-resolved fluorescence probe for the SNAP tag. Sensitivity
      was not enhanced, however, for the CLIP tag, possibly due to higher levels of
      nonspecific binding. CONCLUSIONS AND IMPLICATIONS: These studies demonstrate that
      highly sensitive and quantitative assays that monitor cell surface CB(1) and
      OX(1) receptors and their internalization by agonists can be developed based on
      introduction of variants of O(6)-alkylguanine-DNA-alkyltransferase into the N
      terminal domain of the receptor. This should be equally suitable for other G
      protein-coupled receptors.

PMID- 21175570
TI  - Inhibition of fatty acid amide hydrolase unmasks CB1 receptor and TRPV1 channel
      mediated modulation of glutamatergic synaptic transmission in midbrain
      periaqueductal grey.
AB  - BACKGROUND AND PURPOSE: While arachidonyl ethanolamine (anandamide) produces
      pharmacological effects mediated by cannabinoid CB1 receptors, it is also an
      agonist at the transient receptor potential vanilloid type 1 (TRPV1) ion channel.
      This study examined the cellular actions of anandamide in the midbrain
      periaqueductal grey (PAG), a region implicated in the analgesic actions of
      cannabinoids, and which expresses both CB1 receptors and TRPV1. EXPERIMENTAL
      APPROACH: In vitro whole cell patch clamp recordings of glutamatergic excitatory
      postsynaptic currents (EPSCs) were made from rat and mouse PAG slices. KEY
      RESULTS: Capsaicin (1 uM) increased the rate, but not the amplitude of miniature
      EPSCs in subpopulations of neurons throughout the rat and mouse PAG. Capsaicin
      had no effect on miniature EPSCs in PAG neurons from TRPV1 knock-out mice. In
      mouse PAG neurons, anandamide (30 uM) had no effect on the rate of miniature
      EPSCs alone, or in the presence of either the CB1 antagonist AM251 (3 uM) or the
      TRPV1 antagonist iodoresiniferatoxin (300 nM). Anandamide produced a decrease in
      miniature EPSC rate in the presence of the fatty acid amide hydrolase (FAAH)
      inhibitor URB597 (1 uM). By contrast, anandamide produced an increase in
      miniature EPSC rate in the presence of both URB597 and AM251, which was absent in
      TRPV1 knock-out mice. CONCLUSIONS AND IMPLICATIONS: These results suggest that
      the actions of anandamide within PAG are limited by enzymatic degradation by
      FAAH. FAAH blockade unmasks both presynaptic inhibition and excitation of
      glutamatergic synaptic transmission which are mediated via CB1 receptors and
      TRPV1 respectively.

PMID- 21175571
TI  - Chronic administration of BMS309403 improves endothelial function in
      apolipoprotein E-deficient mice and in cultured human endothelial cells.
AB  - BACKGROUND AND PURPOSE: Adipocyte fatty acid-binding protein (A-FABP) is up
      regulated in regenerated endothelial cells and modulates inflammatory responses
      in macrophages. Endothelial dysfunction accompanying regeneration is accelerated
      by hyperlipidaemia. Here, we investigate the contribution of A-FABP to the
      pathogenesis of endothelial dysfunction in the aorta of apolipoprotein E
      deficient (ApoE(-/-) ) mice and in cultured human endothelial cells. EXPERIMENTAL
      APPROACH: A-FABP was measured in aortae of ApoE(-/-) mice and human endothelial
      cells by RT-PCR, immunostaining and immunoblotting. Total and phosphorylated
      forms of endothelial nitric oxide synthase (eNOS) were measured by
      immunoblotting. Changes in isometric tension were measured in rings of mice
      aortae KEY RESULTS: A-FABP was expressed in aortic endothelium of ApoE(-/-) mice
      aged 12 weeks and older, but not at 8 weeks or in C57 wild-type mice. Reduced
      endothelium-dependent relaxations to acetylcholine, UK14304 (selective alpha(2) 
      adrenoceptor agonist) and A23187 (calcium ionophore) and decreased protein
      presence of phosphorylated and total eNOS were observed in aortae of 18 week-old
      ApoE(-/-) mice compared with age-matched controls. A 6 week treatment with the A
      FABP inhibitor, BMS309403, started in 12 week-old mice, improved endothelial
      function, phosphorylated and total eNOS and reduced plasma triglyceride levels
      but did not affect endothelium-independent relaxations. The beneficial effect of
      BMS309403 on UK14304-induced relaxations was attenuated by Pertussis toxin. In
      cultured human microvascular endothelial cells, lipid-induced A-FABP expression
      was associated with reduced phosphorylated eNOS and NO production and was
      reversed by BMS309403. CONCLUSIONS AND IMPLICATIONS: Elevated expression of A
      FABP in endothelial cells contributes to their dysfunction both in vivo and in
      vitro.

PMID- 21175572
TI  - Trapping and dissociation of propafenone derivatives in HERG channels.
AB  - BACKGROUND AND PURPOSE: Human ether-a-go-go related gene (HERG) channel
      inhibitors may be subdivided into compounds that are trapped in the closed
      channel conformation and others that dissociate at rest. The structural
      peculiarities promoting resting state dissociation from HERG channels are
      currently unknown. A small molecule-like propafenone is efficiently trapped in
      the closed HERG channel conformation. The aim of this study was to identify
      structural moieties that would promote dissociation of propafenone derivatives.
      EXPERIMENTAL APPROACH: Human ether-a-go-go related gene channels were
      heterologously expressed in Xenopus oocytes and potassium currents were recorded
      using the two-microelectrode voltage clamp technique. Recovery from block by 10
      propafenone derivatives with variable side chains, but a conserved putative
      pharmacophore, was analysed. KEY RESULTS: We have identified structural
      determinants of propafenone derivatives that enable drug dissociation from the
      closed channel state. Propafenone and four derivatives with 'short' side chains
      were trapped in the closed channel. Five out of six bulky derivatives efficiently
      dissociated from the channel at rest. One propafenone derivative with a similar
      bulk but lacking an H-bond acceptor in this region was trapped. Correlations were
      observed between molecular weight and onset of channel block as well as between
      pK(a) and recovery at rest. CONCLUSION AND IMPLICATIONS: The data show that
      extending the size of a trapped HERG blocker-like propafenone by adding a bulky
      side chain may impede channel closure and thereby facilitate drug dissociation at
      rest. The presence of an H-bond acceptor in the bulky side chain is, however,
      essential.

PMID- 21175574
TI  - Effects on resting cerebral blood flow and functional connectivity induced by
      metoclopramide: a perfusion MRI study in healthy volunteers.
AB  - BACKGROUND AND PURPOSE The substituted benzamide, metoclopramide, is a dopamine
      receptor antagonist and is widely prescribed in the symptomatic treatment of
      nausea and vomiting, although it can cause adverse motor and non-motor side
      effects. The effects of metoclopramide on brain metabolism have not been
      investigated to date. EXPERIMENTAL APPROACH To determine the effects of
      metoclopramide on brain function, cerebral perfusion changes after a single oral
      dose were assessed in healthy volunteers using magnetic resonance imaging (MRI)
      techniques. Arterial spin labelling (ASL) perfusion MRI was used to measure
      cerebral blood flow before and after metoclopramide. Blood haemodynamics in the
      vertebral and internal carotid arteries were evaluated using phase-contrast MRI.
      KEY RESULTS Metoclopramide altered haemodynamics in the carotid arteries and the
      cerebral perfusion. Perfusion increased bilaterally in the putamen, consistent
      with antagonism of dopamine D(2) receptors by metoclopramide and possibly related
      to its motor side effects. In contrast, reduced perfusion was observed in the
      insular cortices and anterior temporal lobes. In addition, functional
      connectivity between the insular cortex and the dorsolateral prefrontal cortex
      was decreased. These cortical changes affecting neural circuits between high
      order association areas may underlie certain neuropsychiatric conditions
      occasionally reported after metoclopramide administration. CONCLUSIONS AND
      IMPLICATIONS The present results show the sensitivity of ASL to detect small
      changes in regional blood flow, closely related to brain function, after a single
      pharmacological challenge, highlighting the potential of this technique for human
      pharmacological studies.

PMID- 21175573
TI  - Development of radiotracers for oncology--the interface with pharmacology.
AB  - There is an increasing role for positron emission tomography (PET) in oncology,
      particularly as a component of early phase clinical trials. As a non-invasive
      functional imaging modality, PET can be used to assess both pharmacokinetics and
      pharmacodynamics of novel therapeutics by utilizing radiolabelled compounds.
      These studies can provide crucial information early in the drug development
      process that may influence the further development of novel therapeutics. PET
      imaging probes can also be used as early biomarkers of clinical response and to
      predict clinical outcome prior to the administration of therapeutic agents. We
      discuss the role of PET imaging particularly as applied to phase 0 studies and
      discuss the regulations involved in the development and synthesis of novel
      radioligands. The review also discusses currently available tracers and their
      role in the assessment of pharmacokinetics and pharmacodynamics as applied to
      oncology.

PMID- 21175575
TI  - The novel phospho-non-steroidal anti-inflammatory drugs, OXT-328, MDC-22 and MDC
      917, inhibit adjuvant-induced arthritis in rats.
AB  - BACKGROUND AND PURPOSE: The use of non-steroidal anti-inflammatory drugs (NSAIDs)
      in the treatment of rheumatoid arthritis (RA) is limited by their toxicity. We
      evaluated the anti-inflammatory efficacy and safety of three novel modified
      NSAIDs, phospho-aspirin, phospho-ibuprofen and phospho-sulindac. EXPERIMENTAL
      APPROACH: We determined the anti-inflammatory effects and gastrointestinal safety
      of the phospho-NSAIDs in the rat adjuvant arthritis model and studied their
      mechanism of action in cultured cells, Cytokines were measured with elisa and
      activation of nuclear factor-kappaB (NF-kappaB) by immunohistochemistry. KEY
      RESULTS: All three phospho-NSAIDs showed less gastrointestinal toxicity than
      their parent compounds and demonstrated strong anti-inflammatory effects,
      essentially reversing joint inflammation and oedema. They have a broad but not
      uniform effect on the expression of relevant cytokines, in general decreasing IL
      6 and IL-1beta and increasing IL-10 levels in rat plasma and cultured cells.
      Phospho-sulindac and phospho-ibuprofen but not phospho-aspirin suppressed PGE(2)
      production in vitro, whereas phospho-aspirin (in contrast to aspirin) showed the
      same effect in vivo. In joint tissues, phospho-aspirin inhibited NF-kappaB
      activation, and suppressed inflammation and bone resorption. Phospho-aspirin also
      inhibited Jurkat T cell proliferation. In general, phospho-aspirin had greater
      efficacy but different effects upon inflammatory mediators compared with aspirin.
      The chemical modification of the parent NSAIDs seems crucial for their safety and
      efficacy. CONCLUSIONS AND IMPLICATIONS: Phospho-aspirin, phospho-ibuprofen and
      phospho-sulindac were safer than their parent NSAIDs, were highly effective in
      rat adjuvant arthritis and inhibited many key mediators in the pathophysiology of
      RA. These novel compounds are promising candidate drugs for the treatment of RA
      and merit further evaluation.

PMID- 21175576
TI  - Animal modelling of traumatic brain injury in preclinical drug development: where
      do we go from here?
AB  - Traumatic brain injury (TBI) is the leading cause of death and disability in
      young adults. Survivors of TBI frequently suffer from long-term personality
      changes and deficits in cognitive and motor performance, urgently calling for
      novel pharmacological treatment options. To date, all clinical trials evaluating
      neuroprotective compounds have failed in demonstrating clinical efficacy in
      cohorts of severely injured TBI patients. The purpose of the present review is to
      describe the utility of animal models of TBI for preclinical evaluation of
      pharmacological compounds. No single animal model can adequately mimic all
      aspects of human TBI owing to the heterogeneity of clinical TBI. To successfully
      develop compounds for clinical TBI, a thorough evaluation in several TBI models
      and injury severities is crucial. Additionally, brain pharmacokinetics and the
      time window must be carefully evaluated. Although the search for a single
      compound, 'silver bullet' therapy is ongoing, a combination of drugs targeting
      various aspects of neuroprotection, neuroinflammation and regeneration may be
      needed. In summary, finding drugs and prove clinical efficacy in TBI is a major
      challenge ahead for the research community and the drug industry. For a
      successful translation of basic science knowledge to the clinic to occur we
      believe that a further refinement of animal models and functional outcome methods
      is important. In the clinical setting, improved patient classification, more
      homogenous patient cohorts in clinical trials, standardized treatment strategies,
      improved central nervous system drug delivery systems and monitoring of target
      drug levels and drug effects is warranted.

PMID- 21175577
TI  - New perspectives for the treatment of pulmonary hypertension.
AB  - Pulmonary hypertension (PH) is a debilitating disease with a poor prognosis.
      Therapeutic options remain limited despite the introduction of prostacyclin
      analogues, endothelin receptor antagonists and phosphodiesterase 5 inhibitors
      within the last 15 years; these interventions address predominantly the
      endothelial and vascular dysfunctionS associated with the condition, but simply
      delay progression of the disease rather than offer a cure. In an attempt to
      improve efficacy, emerging approaches have focused on targeting the pro
      proliferative phenotype that underpins the pulmonary vascular remodelling in the
      lung and contributes to the impaired circulation and right heart failure. Many
      novel targets have been investigated and validated in animal models of PH,
      including modulation of guanylate cyclases, phosphodiesterases, tyrosine kinases,
      Rho kinase, bone morphogenetic proteins signalling, 5-HT, peroxisome proliferator
      activator receptors and ion channels. In addition, there is hope that
      combinations of such treatments, harnessing and optimizing vasodilator and anti
      proliferative properties, will provide a further, possibly synergistic, increase
      in efficacy; therapies directed at the right heart may also offer an additional
      benefit. This overview highlights current therapeutic options, promising new
      therapies, and provides the rationale for a combination approach to treat the
      disease.

PMID- 21175578
TI  - Does airway smooth muscle express an inflammatory phenotype in asthma?
AB  - In addition to hyperresponsiveness in asthma, airway smooth muscle (ASM) also
      manifests an inflammatory phenotype characterized by augmented expression of
      mediators that enhance inflammation, contribute to tissue remodelling and augment
      leucocyte trafficking and activity. Our present review summarizes contemporary
      understanding of ASM-derived mediators and their paracrine and autocrine actions
      in airway diseases.

PMID- 21175579
TI  - Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP
      channels and endocannabinoid metabolic enzymes.
AB  - BACKGROUND AND PURPOSE: Cannabidiol (CBD) and Delta(9) -tetrahydrocannabinol
      (THC) interact with transient receptor potential (TRP) channels and enzymes of
      the endocannabinoid system. EXPERIMENTAL APPROACH: The effects of 11 pure
      cannabinoids and botanical extracts [botanical drug substance (BDS)] from
      Cannabis varieties selected to contain a more abundant cannabinoid, on TRPV1,
      TRPV2, TRPM8, TRPA1, human recombinant diacylglycerol lipase alpha (DAGLalpha),
      rat brain fatty acid amide hydrolase (FAAH), COS cell monoacylglycerol lipase
      (MAGL), human recombinant N-acylethanolamine acid amide hydrolase (NAAA) and
      anandamide cellular uptake (ACU) by RBL-2H3 cells, were studied using
      fluorescence-based calcium assays in transfected cells and radiolabelled
      substrate-based enzymatic assays. Cannabinol (CBN), cannabichromene (CBC), the
      acids (CBDA, CBGA, THCA) and propyl homologues (CBDV, CBGV, THCV) of CBD,
      cannabigerol (CBG) and THC, and tetrahydrocannabivarin acid (THCVA) were also
      tested. KEY RESULTS: CBD, CBG, CBGV and THCV stimulated and desensitized human
      TRPV1. CBC, CBD and CBN were potent rat TRPA1 agonists and desensitizers, but
      THCV-BDS was the most potent compound at this target. CBG-BDS and THCV-BDS were
      the most potent rat TRPM8 antagonists. All non-acid cannabinoids, except CBC and
      CBN, potently activated and desensitized rat TRPV2. CBDV and all the acids
      inhibited DAGLalpha. Some BDS, but not the pure compounds, inhibited MAGL. CBD
      was the only compound to inhibit FAAH, whereas the BDS of CBC > CBG > CBGV
      inhibited NAAA. CBC = CBG > CBD inhibited ACU, as did the BDS of THCVA, CBGV,
      CBDA and THCA, but the latter extracts were more potent inhibitors. CONCLUSIONS
      AND IMPLICATIONS: These results are relevant to the analgesic, anti-inflammatory
      and anti-cancer effects of cannabinoids and Cannabis extracts.

PMID- 21175580
TI  - Role of angiotensin II receptor subtype activation in cognitive function and
      ischaemic brain damage.
AB  - Recent clinical studies have demonstrated that angiotensin II type 1 (AT(1) )
      receptor blockers (ARBs) reduce the onset of stroke, stroke severity and the
      incidence and progression of Alzheimer's disease and dementia. We can expect that
      ARBs exert these effects by both AT(1) receptor blockade and angiotensin II type
      2 (AT(2) ) receptor stimulation. Moreover, recent experimental results support
      the notion that AT(2) receptor stimulation with AT(1) receptor blockade could
      contribute to protection against ischaemic brain damage at least partly due to an
      increase in cerebral blood flow and decrease in oxidative stress, and prevent
      cognitive decline. Cellular therapy has been focused on as a new therapeutic
      approach to restore injured neurons. In this context, it has been reported that
      AT(2) receptor stimulation enhances neurite outgrowth and decreases neural
      damage, thereby enhancing neurogenesis. Moreover, additional beneficial effects
      of ARBs with an AT(1) receptor blocking action with a partial peroxisome
      proliferator-activated receptor (PPAR)-gamma agonistic effect have been reported,
      and interaction of AT(2) receptor activation and PPAR-gamma might be involved in
      these ARBs' effects. This article reviews the effects of regulation of activation
      of angiotensin II receptor subtypes on ischaemic brain damage and cognitive
      function, focusing on the effects of AT(2) receptor stimulation.

PMID- 21175581
TI  - Low dose of the liver X receptor agonist, AZ876, reduces atherosclerosis in
      APOE*3Leiden mice without affecting liver or plasma triglyceride levels.
AB  - BACKGROUND AND PURPOSE: Liver X receptor (LXR) agonists are atheroprotective but
      often induce hypertriglyceridaemia and liver steatosis. We investigated the
      effect of a novel high-affinity LXR activator, AZ876, on plasma lipids,
      inflammation and atherosclerosis, and compared the effects with another LXR
      agonist, GW3965. EXPERIMENTAL APPROACH: APOE*3Leiden mice were fed an atherogenic
      diet alone or supplemented with either AZ876 (5 or 20umol.kg(-1) .day(-1) ) or
      GW3965 (17umol.kg(-1) .day(-1) ) for 20 weeks. Total cholesterol and triglyceride
      levels were measured using commercial kits. Plasma cytokines were determined by
      using bead-based multiplex suspension array kits with the Luminex technology.
      Atherosclerosis was assessed histochemically and lesion composition was assessed
      by immunohistochemical methods. KEY RESULTS: Low-dose AZ876 had no effect on
      plasma or liver lipids, whereas high-dose AZ876 increased plasma triglycerides
      (+110%) and reduced cholesterol (-16%) compared with controls. GW3965 increased
      plasma triglycerides (+70%). Low-dose AZ876 reduced lesion area (-47%); and high
      dose AZ876 strongly decreased lesion area (-91%), lesion number (-59%) and
      severity. In either dose, AZ876 did not affect lesion composition. GW3965 reduced
      atherosclerosis and collagen content of lesions (-23%; P < 0.01). High-dose AZ876
      and GW3965, but not low-dose AZ876, reduced inflammation as reflected by lower
      cytokine levels and vessel wall activation. CONCLUSIONS AND IMPLICATIONS: We have
      identified a novel LXR agonist that when given in a low dose inhibits the
      progression of atherosclerosis without inducing anti-inflammatory effects, liver
      steatosis or hypertriglyceridaemia. Therefore, the primary protective action of a
      low-dose AZ876 is likely to be an increased reverse cholesterol transport.

PMID- 21175582
TI  - Ca2+ entry following P2X receptor activation induces IP3 receptor-mediated Ca2+
      release in myocytes from small renal arteries.
AB  - BACKGROUND AND PURPOSE: P2X receptors mediate sympathetic control and
      autoregulation of the renal circulation triggering contraction of renal vascular
      smooth muscle cells (RVSMCs) via an elevation of intracellular Ca(2+)
      concentration ([Ca(2+) ](i) ). Although it is well-appreciated that the myocyte
      Ca(2+) signalling system is composed of microdomains, little is known about the
      structure of the [Ca(2+) ](i) responses induced by P2X receptor stimulation in
      vascular myocytes. EXPERIMENTAL APPROACHES: Using confocal microscopy, perforated
      patch electrical recordings, immuno-/organelle-specific staining, flash
      photolysis and RT-PCR analysis we explored, at the subcellular level, the Ca(2+)
      signalling system engaged in RVSMCs on stimulation of P2X receptors with the
      selective agonist alphabeta-methylene ATP (alphabeta-meATP). KEY RESULTS: RT-PCR
      analysis of single RVSMCs showed the presence of genes encoding inositol 1,4,5
      trisphosphate receptor type 1(IP(3) R1) and ryanodine receptor type 2 (RyR2). The
      amplitude of the [Ca(2+) ](i) transients depended on alphabeta-meATP
      concentration. Depolarization induced by 10 umol.L(-1) alphabeta-meATP triggered
      an abrupt Ca(2+) release from sub-plasmalemmal ('junctional') sarcoplasmic
      reticulum enriched with IP(3) Rs but poor in RyRs. Depletion of calcium stores,
      block of voltage-gated Ca(2+) channels (VGCCs) or IP(3) Rs suppressed the sub
      plasmalemmal [Ca(2+) ](i) upstroke significantly more than block of RyRs. The
      effect of calcium store depletion or IP(3) R inhibition on the sub-plasmalemmal
      [Ca(2+) ](i) upstroke was attenuated following block of VGCCs. CONCLUSIONS AND
      IMPLICATIONS: Depolarization of RVSMCs following P2X receptor activation induces
      IP(3) R-mediated Ca(2+) release from sub-plasmalemmal ('junctional') sarcoplasmic
      reticulum, which is activated mainly by Ca(2+) influx through VGCCs. This
      mechanism provides convergence of signalling pathways engaged in
      electromechanical and pharmacomechanical coupling in renal vascular myocytes.

PMID- 21175584
TI  - Geranylated flavanone tomentodiplacone B inhibits proliferation of human
      monocytic leukaemia (THP-1) cells.
AB  - BACKGROUND AND PURPOSE: Paulownia tomentosa is a rich source of geranylated
      flavanones, some of which we have previously shown to have cytotoxic activity. To
      identify members of this class of compounds with cytostatic effects, we assessed
      the effects of the geranylated flavanone tomentodiplacone B (TOM B) on cell cycle
      progression and cell cycle regulatory pathways of THP-1 human monocytic leukaemia
      cells. EXPERIMENTAL APPROACH: Cell viability was measured by dye exclusion and
      proliferation by WST-1 assays; cell cycle was monitored by flow cytometry.
      Regulatory proteins were assessed by immunoprecipitation and kinase assays, and
      Western blotting. KEY RESULTS: Tomentodiplacone B had no effect during the first
      24 h of cell growth at concentrations between 1 and 2.5 uM, but inhibited cell
      growth in a dose-dependent manner at concentrations of 5 uM or higher. Growth
      inhibition during the first 24 h of exposure to TOM B was not accompanied by
      cytotoxicity as cells were accumulated in G1 phase dose-dependently. This G1
      phase accumulation was associated with down-regulation of cyclin-dependent kinase
      2 activity and also protein levels of cyclins E1 and A2. However, key stress
      related molecules (gamma-H2AX, p53 and p21) were not induced, suggesting that TOM
      B acts by directly inhibiting the cyclin-dependent kinase 2 signalling pathway
      rather than initiating DNA damage or cellular stress. CONCLUSIONS AND
      IMPLICATIONS: Our study provides the first evidence that TOM B directly inhibits
      proliferation of human monocytic leukaemia cells, and thus is a potential
      anticancer agent, preventing leukaemia cells from progressing from G1 phase into
      DNA synthesis.

PMID- 21175583
TI  - Biochemical characterization of a novel high-affinity and specific plasma
      kallikrein inhibitor.
AB  - BACKGROUND AND PURPOSE: Kallikrein acts on high molecular weight kininogen (HK)
      to generate HKa (cleaved HK) and bradykinin (BK). BK exerts its effects by
      binding to B(2) receptors. The activation of B(2) receptors leads to the
      formation of tissue plasminogen activator, nitric oxide (NO) and prostacyclin
      (PGI(2) ). An elevated kallikrein-dependent pathway has been linked to
      cardiovascular disease risk. The aim of this study was to investigate whether our
      novel plasma kallikrein inhibitor abolishes kallikrein-mediated generation of BK
      from HK and subsequent BK-induced NO and PGI(2) formation, thereby influencing
      endothelial pathophysiology during chronic inflammatory diseases. EXPERIMENTAL
      APPROACH: Kinetic analysis was initially used to determine the potency of PF
      04886847. Biochemical ligand binding assays, immunological methods and calcium
      flux studies were used to determine the selectivity of the kallikrein inhibitor.
      In addition, the effect of PF-04886847 on BK-induced relaxation of the rat aortic
      ring was determined in a model of lipopolysaccharide-induced tissue inflammation.
      KEY RESULTS: Evidence was obtained in vitro and in situ, indicating that PF
      04886847 is a potent and specific inhibitor of plasma kallikrein. PF-04886847
      efficiently blocked calcium influx as well as NO and PGI(2) formation mediated
      through the BK-stimulated B(2) receptor signalling pathway. PF-04886847 blocked
      kallikrein-induced endothelial-dependent relaxation of isolated rat aortic rings
      pre-contracted with phenylephrine. CONCLUSIONS AND IMPLICATIONS: PF-04886847 was
      shown to be the most potent small molecule inhibitor of plasma kallikrein yet
      described; it inhibited kallikrein in isolated aortic rings and cultured
      endothelial cells. Overall, our results indicate that PF-04886847 would be useful
      for the treatment of kallikrein-mediated inflammatory disorders.

PMID- 21175585
TI  - The protective effect of tianeptine on Gp120-induced apoptosis in astroglial
      cells: role of GS and NOS, and NF-kappaB suppression.
AB  - BACKGROUND AND PURPOSE: Tianeptine is an antidepressant affecting the
      glutamatergic system. In spite of its proven clinical efficacy, molecular effects
      of tianeptine are not entirely clear. Tianeptine modulates cytokine expression in
      the CNS and protects the hippocampus from chronic stress effects. HIV infection
      is associated with inflammation and neuronal loss, causing HIV-associated
      dementia (HAD). The human immunodeficiency virus type-1 glycoprotein gp120 has
      been proposed as a likely aetiological agent of HAD. In this study, we determined
      whether tianeptine protects astroglial cells from the neurodegenerative effects
      of gp120. EXPERIMENTAL APPROACH: Human astroglial cells were treated with gp120
      and tianeptine, and viability and apoptosis was monitored by TUNEL, annexin V,
      and activated caspase-3 staining and flow cytometry. Protein levels of glutamine
      synthase (GS), inducible and constitutive nitric oxide synthases (iNOS, cNOS) and
      nuclear factor kappaB (NF-kappaB) pathway were determined by Western blot
      analysis. The respective activities were assessed indirectly by measuring
      glutamine and nitrite concentrations or by luciferase reporter assays. KEY
      RESULTS: Tianeptine showed an anti-apoptotic effect and prevented caspase-3
      activation by gp120. The mechanism of tianeptine's action involved GS and cNOS
      stabilization and iNOS suppression. Moreover, tianeptine increased IkappaB-alpha
      levels in the absence of gp120 and blocked its degradation in response to gp120.
      This correlated with the suppression of basal and gp120-induced NF-kappaB
      transcriptional activity. CONCLUSIONS AND IMPLICATIONS: Tianeptine clearly exerts
      neuroprotective effects in vitro by suppressing the molecular pro-inflammatory
      effects of gp120. Studies in animal models should be performed to evaluate the
      potential of tianeptine as a treatment for HAD.

PMID- 21175586
TI  - Arrestins differentially regulate histamine- and oxytocin-evoked phospholipase C
      and mitogen-activated protein kinase signalling in myometrial cells.
AB  - BACKGROUND AND PURPOSE: The uterotonins oxytocin and histamine, mediate
      contractile signals through specific G protein-coupled receptors, a process which
      is tightly controlled during gestation to prevent preterm labour. We previously
      identified G protein-coupled receptor kinase (GRK)2 and GRK6 as respective
      cardinal negative regulators of histamine H(1) and oxytocin receptor signalling.
      GRK-mediated phosphorylation promotes arrestin recruitment, not only
      desensitizing receptors but activating an increasing number of diverse signalling
      pathways. Here we investigate potential roles that arrestins play in the
      regulation of myometrial oxytocin/histamine H(1) receptor signalling.
      EXPERIMENTAL APPROACH: Endogenous arrestins2 and 3 were specifically depleted
      using RNA-interference in a human myometrial cell line and the consequences of
      this for G protein-coupled receptor-mediated signalling were assessed using
      Ca(2+) /inositol 1,4,5-trisphophate imaging and standard mitogen-activated
      protein kinase (MAPK) assays. KEY RESULTS: Depletion of arrestin3, but not
      arrestin2 enhanced and prolonged H(1) receptor-stimulated Ca(2+) responses,
      whilst depletion of either arrestin increased oxytocin receptor responses.
      Arrestin3 depletion decreased H(1) receptor desensitization, whilst removal of
      either arrestin isoform was equally effective in preventing oxytocin receptor
      desensitization. Following arrestin3 depletion oxytocin-induced phospho
      extracellular signal-regulated kinase1/2 signals were diminished and histamine
      stimulated signals virtually absent, whereas depletion of arrestin2 augmented
      extracellular signal-regulated kinase1/2 responses to each agonist. Conversely,
      depletion of arrestin3 enhanced p38 signals to each agonist, whilst arrestin2
      suppression increased oxytocin-, but not histamine-induced p38 MAPK responses.
      CONCLUSIONS AND IMPLICATIONS: Arrestin proteins are key regulators of H(1) and
      oxytocin receptor desensitization, and play integral roles mediating uterotonin
      stimulated MAPK-signalling. These data provide insights into the in situ
      regulation of these receptor subtypes and may inform pathophysiological
      functioning in preterm labour.

PMID- 21175587
TI  - Mitochondrial genome depletion dysregulates bile acid- and paracetamol-induced
      expression of the transporters Mdr1, Mrp1 and Mrp4 in liver cells.
AB  - BACKGROUND AND PURPOSE: Mitochondria are involved in the toxicity of several
      compounds, retro-control of gene expression and apoptosis activation. The effect
      of mitochondrial genome (mtDNA) depletion on changes in ABC transporter protein
      expression in response to bile acids and paracetamol was investigated.
      EXPERIMENTAL APPROACH: Hepa 1-6 mouse hepatoma cells with 70% decrease in 16S/18S
      rRNA ratio (Rho cells) were obtained by long-term treatment with ethidium
      bromide. KEY RESULTS: Spontaneous apoptosis and reactive oxygen species (ROS)
      generation were decreased in Rho cells. Following glycochenodeoxycholic acid
      (GCDCA) or paracetamol, Rho cells generated less ROS and were more resistant to
      cell death. Apoptosis induced by GCDCA and Fas was also reduced. The basal
      expression of Mdr1 was significantly enhanced, but this was not further
      stimulated by GCDCA or paracetamol, as observed in wild-type (WT) cells. Basal
      expression of Mrp1 and Mrp4 was similar in WT and Rho cells, whereas they were up
      regulated only in WT cells after GCDCA or paracetamol, along with the
      transcription factors Shp and Nrf2, but not Fxr or Pxr. Increased expression of
      Nrf2 was accompanied by its enhanced nuclear translocation. Glycoursodeoxycholic
      acid failed to cause any of the effects observed for GCDCA or paracetamol.
      CONCLUSIONS AND IMPLICATIONS: The Nrf2-mediated pathway is partly independent of
      ROS production. Nuclear translocation of Nrf2 is insufficient to up-regulate
      Mdr1, Mrp1 and Mrp4, which requires the participation of other regulatory
      element(s) whose activation in response to GCDCA and paracetamol is impaired in
      Rho cells and hence probably sensitive to ROS.

PMID- 21175588
TI  - Pharmacological enhancement of fear reduction: preclinical models.
AB  - Anxiety disorders have a high prevalence, and despite the substantial advances in
      the psychological treatment of anxiety, relapse is still a common problem. One
      approach to improving existing psychological treatments for anxiety has been to
      develop pharmacological agents that can be used to enhance the processes
      underlying exposure therapy, which is the most commonly used and empirically
      validated psychological treatment for anxiety during which individuals are taught
      to appropriately inhibit fear. Animal models of exposure therapy, particularly
      fear extinction, have proved to be a very useful way of examining the neural and
      molecular correlates of fear inhibition, which has in turn led to the
      identification of numerous drugs that enhance these processes in rats. Several of
      these drugs have subsequently been tested as novel pharmacological adjuncts to
      exposure therapy in humans with a range of anxiety disorders. The purpose of this
      review is to outline the key animal models of exposure therapy and to describe
      how these have been used to develop potential pharmacological adjuncts for
      anxiety disorders. Drugs that are currently in clinical use, as well as those
      currently in the preclinical stages of investigation, are described.

PMID- 21175589
TI  - Regulation of nausea and vomiting by cannabinoids.
AB  - Considerable evidence demonstrates that manipulation of the endocannabinoid
      system regulates nausea and vomiting in humans and other animals. The anti-emetic
      effect of cannabinoids has been shown across a wide variety of animals that are
      capable of vomiting in response to a toxic challenge. CB(1) agonism suppresses
      vomiting, which is reversed by CB(1) antagonism, and CB(1) inverse agonism
      promotes vomiting. Recently, evidence from animal experiments suggests that
      cannabinoids may be especially useful in treating the more difficult to control
      symptoms of nausea and anticipatory nausea in chemotherapy patients, which are
      less well controlled by the currently available conventional pharmaceutical
      agents. Although rats and mice are incapable of vomiting, they display a
      distinctive conditioned gaping response when re-exposed to cues (flavours or
      contexts) paired with a nauseating treatment. Cannabinoid agonists (Delta(9) 
      THC, HU-210) and the fatty acid amide hydrolase (FAAH) inhibitor, URB-597,
      suppress conditioned gaping reactions (nausea) in rats as they suppress vomiting
      in emetic species. Inverse agonists, but not neutral antagonists, of the CB(1)
      receptor promote nausea, and at subthreshold doses potentiate nausea produced by
      other toxins (LiCl). The primary non-psychoactive compound in cannabis,
      cannabidiol (CBD), also suppresses nausea and vomiting within a limited dose
      range. The anti-nausea/anti-emetic effects of CBD may be mediated by indirect
      activation of somatodendritic 5-HT(1A) receptors in the dorsal raphe nucleus;
      activation of these autoreceptors reduces the release of 5-HT in terminal
      forebrain regions. Preclinical research indicates that cannabinioids, including
      CBD, may be effective clinically for treating both nausea and vomiting produced
      by chemotherapy or other therapeutic treatments.

PMID- 21175590
TI  - The ABCG family of membrane-associated transporters: you don't have to be big to
      be mighty.
AB  - Along with many other mammalian ATP-binding cassette (ABC) transporters, members
      of the ABCG group are involved in the regulated transport of hydrophobic
      compounds across cellular membranes. In humans, five ABCG family members have
      been identified, encoding proteins ranging from 638 to 678 amino acids in length.
      All five have been the subject of intensive investigation to better understand
      their physiological roles, expression patterns, interactions with substrates and
      inhibitors, and regulation at both the transcript and protein level. The
      principal substrates for at least four of the ABCG proteins are endogenous and
      dietary lipids, with ABCG1 implicated in particular in the export of cholesterol,
      and ABCG5 and G8 forming a functional heterodimer responsible for plant sterol
      elimination from the body. ABCG2 has a much broader substrate specificity and its
      ability to transport numerous diverse pharmaceuticals has implications for the
      absorption, distribution, metabolism, excretion and toxicity (ADMETOx) profile of
      these compounds. ABCG2 is one of at least three so-called multidrug resistant ABC
      transporters expressed in humans, and its activity is associated with decreased
      efficacy of anti-cancer agents in several carcinomas. In addition to its role in
      cancer, ABCG2 also plays a role in the normal physiological transport of urate
      and haem, the implications of which are described. We summarize here data on all
      five human ABCG transporters and provide a current perspective on their roles in
      human health and disease.

PMID- 21175591
TI  - New perspectives regarding beta(2) -adrenoceptor ligands in the treatment of
      asthma.
AB  - In the last two decades several significant changes have been proposed in the
      receptor theory that describes how ligands can interact with G protein-coupled
      receptors (GPCRs). Here we briefly summarize the evolution of receptor theory and
      detail recent prominent advances. These include: (i) the existence of
      spontaneously active GPCRs that are capable of signalling even though they are
      unoccupied by any ligand; (ii) the discovery of ligands that can inactivate these
      spontaneously active receptors; (iii) the notion that a ligand may simultaneously
      activate more than one GPCR signalling pathway; and (iv) the notion that certain
      ligands may be able to preferentially direct receptor signalling to a specific
      pathway. Because the data supporting these receptor theory ideas are derived
      primarily from studies using artificial expression systems, the physiological
      relevance of these new paradigms remains in question. As a potential example of
      how these new perspectives in receptor theory relate to drug actions and clinical
      outcomes, we discuss their relevance to the recent controversy regarding the
      chronic use of beta(2) -adrenoceptor agonists in the treatment of asthma.

PMID- 21175592
TI  - Clinical immunology review series: an approach to desensitization.
AB  - Allergen immunotherapy describes the treatment of allergic disease through
      administration of gradually increasing doses of allergen. This form of immune
      tolerance induction is now safer, more reliably efficacious and better understood
      than when it was first formally described in 1911. In this paper the authors aim
      to summarize the current state of the art in immunotherapy in the treatment of
      inhalant, venom and drug allergies, with specific reference to its practice in
      the United Kingdom. A practical approach has been taken, with reference to
      current evidence and guidelines, including illustrative protocols and vaccine
      schedules. A number of novel approaches and techniques are likely to change
      considerably the way in which we select and treat allergy patients in the coming
      decade, and these advances are previewed.

PMID- 21175593
TI  - Increased frequency of immunoglobulin (Ig)A-secreting cells following Toll-like
      receptor (TLR)-9 engagement in patients with Kawasaki disease.
AB  - Kawasaki disease (KD) is an acute vasculitis affecting mainly infants and
      children. Human B cells express Toll-like receptor (TLR)-9, whose natural ligands
      are unmethylated cytosine-guanine dinucleotide (CpG) motifs characteristic of
      bacterial DNA. The aim of this study was to clarify the pathogenesis of KD
      analysing the activation status of peripheral blood mononuclear cells (PBMC),
      focusing on B lymphocyte activation and functions. Ten patients and 10 age
      matched healthy donors were recruited from the Bambino Gesu Hospital of Rome,
      Italy and enrolled into this study. We determined phenotype profile and
      immunoglobulin (Ig) production of PBMC from KD patients and age-matched controls.
      We found that the frequency of CD19(+) B lymphocytes and CD19(+) /CD86(+)
      activated B lymphocytes from KD patients during the acute phase before therapy
      was increased significantly. Moreover, B lymphocytes of acute-phase KD patients
      were more prone to CpG oligodeoxynucleotide (ODN) activation compared with the
      age-matched controls, as assessed by a significant increase of the number of IgA
      secreting cells (SC). In the same patients we found a marked increase of IgM,
      IgG, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha production
      compared with the control group. In addition, in two convalescent KD patients,
      conventional treatment with intravenous immunoglobulin (IVIG) restored the normal
      frequency of CD19(+) B cells, the number of IgA-, IgM- and IgG-SC and the
      production of IL-6 and TNF-alpha. Our findings indicate that the percentages of
      peripheral B lymphocytes of acute-phase KD patients are increased and are prone
      to bacterial activation in terms of increased numbers of IgA-SC and increased
      production of IL-6 and TNF-alpha inflammatory cytokines. Thus, our data support
      the hypothesis of an infectious triggering in KD.

PMID- 21175594
TI  - ADAM metallopeptidase domain 17 (ADAM17) is naturally processed through major
      histocompatibility complex (MHC) class I molecules and is a potential
      immunotherapeutic target in breast, ovarian and prostate cancers.
AB  - Selection of suitable antigens is critical for the development of cancer
      vaccines. Most desirable are over-expressed cell surface proteins that may serve
      as targets for both antibodies and T cells, thus maximizing a concerted immune
      response. Towards this goal, we characterized the relevance of tumour necrosis
      factor-alpha-converting enzyme (ADAM17) for such targeted therapeutics. ADAM17 is
      one of the several metalloproteinases that play a key role in epidermal growth
      factor receptor (EGFR) signalling and has recently emerged as a new therapeutic
      target in several tumour types. In the present study, we analysed the expression
      profile of ADAM17 in a variety of normal and cancer cells of human origin and
      found that this protein is over-expressed on the surface of several types of
      cancer cells compared to the normal counterparts. Furthermore, we analysed the
      presentation of a human leucocyte antigen (HLA)-A2-restricted epitope from ADAM17
      protein to specific T cells established from normal donors as well as ovarian
      cancer patients. Our analysis revealed that the HLA-A2-restricted epitope is
      processed efficiently and presented by various cancer cells and not by normal
      cells. Tumour-specific T cell activation results in the secretion of both
      interferon-gamma and granzyme B that can be blocked by HLA-A2 specific
      antibodies. Collectively, our data present evidence that ADAM17 can be a
      potential target antigen to devise novel immunotherapeutic strategies against
      ovarian, breast and prostate cancer.

PMID- 21175595
TI  - Expansion of regulatory CD8+ CD25+ T cells after neonatal alloimmunization.
AB  - Transplantation tolerance induced by neonatal injection of semi-allogeneic spleen
      cells is associated with a pathological syndrome caused by T helper type 2 (Th2)
      differentiation of donor-specific CD4(+) T lymphocytes. We have shown previously
      that this Th2-biased response is inhibited by host CD8(+) T cells. Herein, we
      demonstrate that upon neonatal immunization with (A/J * BALB/c)F(1) spleen cells,
      BALB/c mice expand a population of CD8(+) T cells expressing both CD25 and
      forkhead box P3 (FoxP3) markers. In this setting, CD8(+) CD25(+) T cells
      predominantly produce interferon (IFN)-gamma and interleukin (IL)-10 and are
      efficient in controlling IL-4, IL-5 and IL-13 production by donor-specific CD4(+)
      T cells in vitro. CD8(+) FoxP3(-) T cells are single producers of IFN-gamma or IL
      10, whereas CD8(+) FoxP3(+) T cells are double producers of IFN-gamma and IL-10.
      We further demonstrate that IFN-gamma and IL-10 are two major cytokines produced
      by CD8(+) T cells involved in the in vivo regulation of Th2-type pathology. In
      this setting, we conclude that neonatal alloimmunization induces the expansion of
      several regulatory CD8(+) T cells which may control Th2 activities via IFN-gamma
      and IL-10.

PMID- 21175597
TI  - Abstracts of the 9th National Medical Genetics Congress. December 1-5, 2010.
      Istanbul, Turkey.

PMID- 21175596
TI  - Serum amyloid A induces reactive oxygen species (ROS) production and
      proliferation of fibroblast.
AB  - Serum amyloid A (SAA) levels are elevated highly in acute phase response and
      elevated slightly and persistently in chronic diseases such as rheumatoid
      arthritis and diabetes. Given that fibroblasts exert profound effects on
      progression of inflammatory chronic diseases, the aim of this study was to
      investigate the response of fibroblasts to SAA. A dose-dependent increase in O(2)
      (-) levels was observed by treatment of fibroblasts with SAA (r = 0.99 and P <=
      0.001). In addition, the expression of p47-phox was up-regulated by SAA (P <
      0.001) and diphenyliodonium (DPI), a nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase inhibitor, reduced the release of O(2) (-) by 50%. Also, SAA
      raised fibroblast proliferation (P < 0.001) and this effect was completely
      abolished by the addition of anti-oxidants (P < 0.001). These findings support
      the notion that, in chronic inflammatory sites, SAA activated fibroblast
      proliferation and ROS production.

PMID- 21175598
TI  - Ring chromosome 22 and neurofibromatosis type II: proof of two-hit model for the
      loss of the NF2 gene in the development of meningioma.
AB  - Carriers of a ring chromosome 22 are mentally retarded and show variable facial
      dysmorphism. They may also present with features of neurofibromatosis type II
      (NF2) such as vestibular schwannomas and multiple meningiomas. In these cases,
      tumourigenesis has been suspected to be caused by the loss of both alleles of the
      NF2 gene, a tumour suppressor localized in 22q12.2. Here, we describe an 18-year
      old patient with constitutional ring chromosome 22 and mental retardation who
      developed rapid-onset spastic paraparesis at the age of 15 years. The causative
      spinal meningioma at the level of T3, which compressed the spinal cord, was
      surgically removed, and the patient regained ambulation. Array comparative
      genomic hybridization (array CGH) and multiplex ligation-dependent probe
      amplification (MLPA) analyses in blood revealed a terminal deletion in 22q13.32,
      not comprising the NF2 gene. In tumour tissue, loss of the whole ring chromosome
      22 including one NF2 gene due to mitotic instability constituted the likely first
      hit, while a point mutation in the other allele of the NF2 gene (c.784C>T,
      p.R262X) was shown as second hit. We review all cases from the literature and
      suggest clinical guidelines for surveillance of patients with ring chromosome 22.

PMID- 21175599
TI  - Congenital myasthenic syndrome associated with epidermolysis bullosa caused by
      homozygous mutations in PLEC1 and CHRNE.
AB  - Mutations in the plectin gene (PLEC1) cause epidermolysis bullosa simplex (EBS),
      which may associate with muscular dystrophy (EBS-MD) or pyloric atresia (EBS-PA).
      The association of EBS with congenital myasthenic syndrome (CMS) is also
      suspected to result from PLEC1 mutations. We report here a consanguineous patient
      with EBS and CMS for whom mutational analysis of PLEC1 revealed a homozygous 36
      nucleotide insertion (1506_1507ins36) that results in a reduced expression of
      PLEC1 mRNA and plectin in the patient muscle. In addition, mutational analysis of
      CHRNE revealed a homozygous 1293insG, which is a well-known low-expressor
      receptor mutation. A skin biopsy revealed signs of EBS, and an anconeus muscle
      biopsy showed signs of a mild myopathy. Endplate studies showed fragmentation of
      endplates, postsynaptic simplification, and large collections of thread-like
      mitochondria. Amplitudes of miniature endplate potentials were diminished, but
      the endplate quantal content was actually increased. The complex phenotype
      presented here results from mutations in two separate genes. While the skin
      manifestations are because of the PLEC1 mutation, footprints of mutations in
      PLEC1 and CHRNE are present at the neuromuscular junction of the patient
      indicating that abnormalities in both genes contribute to the CMS phenotype.

PMID- 21175600
TI  - Do we belittle epilepsy by calling it a disorder rather than a disease?

PMID- 21175601
TI  - Epilepsy and activity--a population-based study.
AB  - PURPOSE: To compare the activity profiles of a nationally representative sample
      of individuals with epilepsy compared to the general population. METHODS: The
      Canadian Community Health Survey is a cross-sectional survey that uses a
      stratified cluster sample design to obtain information on Canadians 12 years of
      age or older. Data on activity and energy expenditure, among those aged 12-39
      years, were compared for those who reported having epilepsy and the remainder of
      the population. RESULTS: Of the 53,552 respondents, 341 reported having epilepsy.
      There was no difference in the monthly frequency of leisure physical activity of
      >15 min duration between those who did and did not have epilepsy. The daily
      energy expenditure related to leisure physical activity was also similar between
      the two groups. The choice of leisure activity was similar, but those with
      epilepsy were more likely to use walking as a leisure physical activity and were
      less likely to be involved in ice hockey, weight training, and home exercise.
      DISCUSSION: These results suggest that the negative attitudes toward restricting
      access to physical activity do not appear to be adversely affecting the leisure
      activity of Canadian youth and young adults with epilepsy.

PMID- 21175602
TI  - Beyond localization: the role of traditional neuropsychological tests in an age
      of imaging.
AB  - Rapid advances in structural and functional magnetic resonance imaging (MRI)
      present two significant challenges to the rationale and role of the traditional
      neuropsychological assessment in the presurgical evaluation of epilepsy surgery
      candidates today. The first is a direct challenge to the model of material
      specific memory that has underpinned much clinical practice over the last 50
      years. The second, more fundamental, challenge goes to the very heart of the
      lateralizing/localizing approach that has been the cornerstone of clinical
      neuropsychology practice in epilepsy surgery centers to date. This review
      examines these challenges and suggests some ways in which the profession might
      respond and adapt. We conclude that noninvasive neuropsychological assessment
      remains a critical investigation in the presurgical evaluation of epilepsy
      surgery patients. Its value stretches beyond the localization of a surgically
      remediable seizure focus. Once a vital test, other investigations are now
      superior in this respect in many cases. However, new technologies have enhanced
      the role of the traditional neuropsychological assessment, which is now able to
      provide unparalleled insights and predictions into the way in which the
      underlying pathology, seizures, and proposed surgery shape an individual's
      profile of cognitive abilities. Detailed neuropsychological feedback enables the
      patient to make an informed decision, and forms the basis of the tailor made
      preemptive rehabilitation programs that can be implemented preoperatively,
      minimizing the most significant morbidity associated with epilepsy surgery today.

PMID- 21175603
TI  - Temporal trends in the mortality of people with epilepsy: a review.
AB  - PURPOSE: It is now generally accepted that people with epilepsy are at increased
      risk of premature death compared with peers in the general population. It has,
      however, not been clearly established how this risk changes over time, nor
      whether mortality rates have been changing over time. METHODS: We carried out a
      systematic review: (1) To determine the pattern of change of mortality risk
      relative to the general population in people with epilepsy in the course of their
      condition as measured by standardized mortality ratios (SMRs), by reviewing
      longitudinal prospective cohort studies. (2) To establish whether there have been
      any changes in reported mortality rates for epilepsy in general populations over
      time. This was complemented by comparison of SMRs in people with epilepsy in the
      same types of source populations (population-based, hospital-based, and
      institutional studies) in different time periods to ascertain any changes in
      reported mortality rates. RESULTS: The SMR is highest in the initial years after
      diagnosis and subsequently decreases. There is a suggestion that there may be an
      increase after 10 years from diagnosis despite the fact that the majority of
      people in these cohorts are in long-term remission. There is no evidence that
      either the overall SMR or the mortality rate of people with epilepsy has changed
      significantly over time. DISCUSSION: Further population and cohort studies are
      needed to confirm these findings.

PMID- 21175604
TI  - Material, modality, or method? Manageable modernization of measurement.

PMID- 21175605
TI  - We are failing our patients: guidelines and quality measures.

PMID- 21175606
TI  - SUDEP, suspected positional airway obstruction, and hypoventilation in postictal
      coma.
AB  - Sudden unexpected death in epilepsy (SUDEP) is the leading cause of mortality in
      patients with chronic uncontrolled epilepsy. Despite intense interest in SUDEP
      from the medical and scientific communities in recent years, its etiologies are
      still largely unresolved. A 35-year-old woman had SUDEP after having a
      generalized seizure in the prone position. The cause of her death was likely
      asphyxia from the convergence of postictal coma and suspected positional airway
      obstruction and hypoventilation, rather than the commonly suspected periictal
      cardiac arrhythmia or central apnea. SUDEP may share a similar etiology with
      sudden infant death syndrome (SIDS) and is likely preventable, at least in a
      proportion of cases.

PMID- 21175607
TI  - Long-term epilepsy surgery outcomes in patients with MRI-negative temporal lobe
      epilepsy.
AB  - PURPOSE: The outcome of surgery in patients with temporal lobe epilepsy (TLE) and
      normal high-resolution magnetic resonance imaging (MRI) has been significantly
      worse than in patients with unilateral hippocampal damage upon MRI. The purpose
      of this study was to determine the long-term outcomes of consecutive true MRI
      negative TLE patients who all underwent standardized preoperative evaluation with
      intracranial electroencephalography (EEG) electrodes. METHODS: In this study we
      present all adult MRI-negative TLE surgery candidates evaluated between January
      1990 and December 2006 at Kuopio Epilepsy Center in Kuopio University Hospital,
      which provides a national center for epilepsy surgery in Finland. During this
      period altogether 146 TLE surgery candidates were evaluated with intracranial
      electrodes, of whom 64 patients with normal high-resolution MRI were included in
      this study. RESULTS: Among the 38 patients who finally underwent surgery, at the
      latest follow-up (mean 5.8 years), 15 (40%) were free of disabling seizures
      (Engel class I) and 6 (16%) were seizure-free (Engel class IA). Twenty-one (55%)
      of 38 patients had poor outcomes (Engel class III-IV). Outcomes did not change
      compared to 12-month follow-up. Histopathologic examination failed to reveal any
      focal pathology in 68% of our MR-negative cases. Only patients with noncongruent
      positron emission tomography (PET) results had worse outcomes (p = 0.044).
      DISCUSSION: Our results suggest that epilepsy surgery outcomes in MRI-negative
      TLE patients are comparable with extratemporal epilepsy surgery in general.
      Seizure outcomes in the long-term also remain stable. Modern imaging techniques
      could further improve the postsurgical seizure-free rate. However, these patients
      usually require chronic intracranial EEG evaluation to define epileptogenic
      areas.

PMID- 21175608
TI  - Effect of levetiracetam on testosterone levels in male patients.
AB  - We sought to determine whether the testosterone increase found with levetiracetam
      exposure in animal studies also occurs in patients. Adult male patients were
      evaluated for reproductive hormone levels before and 1 month after levetiracetam
      therapy. Eight subjects met inclusion/exclusion criteria (mean age 46 years,
      range 29-75 years). Total testosterone prior to starting levetiracetam ranged
      from 206-787 ng/dl [mean 445, standard deviation (SD) 227]. The mean total
      testosterone after levetiracetam therapy increased to 592 ng/dl (range 216-981,
      SD 297), an increase of 16% (p = 0.036). The free testosterone increased from a
      mean of 64 pg/ml (range 36-115, SD 30) to a mean of 76 pg/ml (range 35-155, SD
      44), an increase of 19% (p = 0.080). The magnitude of change in testosterone
      levels correlated with the initial testosterone level (p = 0.038, r = 0.734).
      These results suggest that levetiracetam increases testosterone levels and that
      an initial testosterone level may predict the magnitude of increase.

PMID- 21175609
TI  - Focal reading epilepsy--a rare variant of reading epilepsy: a case report.
AB  - Reading epilepsy is a distinct form of epilepsy in which all or almost all
      seizures are precipitated by reading. Seizures typically show orofacial or jaw
      myoclonus. Nevertheless, reading epilepsy is not homogenous and its
      classification is unclear. We report a patient with reading-induced prolonged
      left temporal seizures, presenting clinically as dyslexia.

PMID- 21175610
TI  - Low blood glucose precipitates spike-and-wave activity in genetically predisposed
      animals.
AB  - PURPOSE: Absence epilepsies are common, with a major genetic contribution to
      etiology. Certain environmental factors can influence absence occurrence but a
      complete understanding of absence precipitation is lacking. Herein we investigate
      if lowering blood glucose increases spike-wave activity in mouse models with
      varying seizure susceptibility. METHODS: Three mouse models were used: an absence
      seizure model based on the knockin of a human GABA(A) gamma2(R43Q) mutation
      (DBA(R43Q)), the spike-wave discharge (SWD)-prone DBA/2J strain, and the seizure
      resistant C57Bl/6 strain. Electrocorticography (ECoG) studies were recorded to
      determine SWDs during hypoglycemia induced by insulin or overnight fasting. KEY
      FINDINGS: An insulin-mediated reduction in blood glucose levels to 4 mm (c.a. 40%
      reduction) was sufficient to double SWD occurrence in the DBA(R43Q) model and in
      the SWD-prone DBA/2J mouse strain. Larger reductions in blood glucose further
      increased SWDs in both these models. However, even with large reductions in blood
      glucose, no discharges were observed in the seizure-resistant C57Bl/6 mouse
      strain. Injection of glucose reversed the impact of insulin on SWDs in the
      DBA(R43Q) model, supporting a reduction in blood glucose as the modulating
      influence. Overnight fasting reduced blood glucose levels to 4.5 mm (c.a. 35%
      reduction) and, like insulin, caused a doubling in occurrence of SWDs.
      SIGNIFICANCE: Low blood glucose can precipitate SWDs in genetically predisposed
      animal models and should be considered as a potential environmental risk factor
      in patients with absence epilepsy.

PMID- 21175611
TI  - Plasma dimethylarginines during the acute inflammatory response.
AB  - INTRODUCTION: Asymmetric dimethylarginine (ADMA) concentrations are increased in
      critically ill patients and may play a role in multiple organ failure. However,
      plasma ADMA concentrations during the development of the inflammatory response
      have not been documented. We measured plasma ADMA, as well as urinary excretion
      of its major metabolite dimethylamine, and nitrate as a marker of nitric oxide
      synthase (NOS) activity, in a cohort of patients undergoing elective knee
      arthroplasty that is known to provoke a significant inflammatory response.
      METHODS: Thirty-eight patients were recruited. Fasting venous blood samples were
      obtained pre-operatively and at 12h and daily until the fifth post-operative day.
      ADMA and symmetric dimethylarginine (SDMA) were measured by high-performance
      liquid chromatography (HPLC). Urinary dimethylamine and nitrate were measured pre
      operatively and on each of the post-operative mornings using HPLC and expressed
      as a ratio to creatinine. RESULTS: Plasma ADMA fell by a median of 31% during the
      post-operative period, reaching a nadir on day 2, and recovering to baseline by
      the end of the study. SDMA showed no significant changes. No increase in urinary
      dimethylamine excretion was noted until day 5 post-op, whereupon it doubled.
      Urinary nitrate showed a small, but nonsignificant decrease on day 2, suggesting
      no major activation of NOS activity. CONCLUSIONS: Plasma ADMA concentration
      decreases rapidly and transiently during the first 48h of acute inflammation.
      This appears not be caused by increased catabolism and may reflect increased
      cellular partitioning. This may serve to regulate NOS activity and prevent
      harmful increases in inducible NOS in situations where it is not appropriate.

PMID- 21175612
TI  - A randomized trial evaluating a block-replacement regimen during radioiodine
      therapy.
AB  - BACKGROUND: Lack of consensus regarding the antithyroid drug regimen in relation
      to radioiodine ((131) I) therapy of hyperthyroidism prompted this randomized
      trial comparing two strategies. DESIGN: Patients with Graves' disease (GD, n =
      51) or toxic nodular goitre (TNG, n = 49) were randomized to (131) I either 8
      days following discontinuation of methimazole (-BRT, n = 52, median dose: 5 mg)
      or while on a continuous block-replacement regimen (+BRT, n = 48, median dose 15
      mg methimazole and 100 MUg levothyroxine). results: Patients in the +BRT group
      required more radioactivity. In this group, thyroid function did not change in
      the early post (131) I period, while serum-free T3 index was higher in the -BRT
      group (P < 0.05). One year posttherapy, the fraction of cured patients (euthyroid
      or hypothyroid) was 48% and 61% in the +BRT and -BRT group, respectively (P =
      0.014 unadjusted; P = 0.004 adjusted), but the outcome depended on the type of
      disease. In GD, treatment failure in the +BRT group correlated positively with
      the 24-h thyroid (131) I uptake (P = 0.017), while no correlations existed in the
      -BRT group. In addition to +BRT allocation, patients with TNG were at higher risk
      of treatment failure with lower thyroid radiation doses (P = 0.048), higher doses
      of methimazole (P = 0.026) and lower levels of serum TSH (P = 0.009).
      CONCLUSIONS: A continuous block-replacement regimen results in a stable thyroid
      function during (131) I therapy but is hampered by the higher amounts of
      radioactivity required. The study demonstrates that the outcome in GD is highly
      unpredictable, while treatment failure in patients with TNG is correlated with a
      number of factors.

PMID- 21175613
TI  - Angiotensin blockade in diabetic patients decreases insulin resistance-associated
      low-grade inflammation.
AB  - BACKGROUND: Insulin-resistant states, such as metabolic syndrome and diabetes
      mellitus type 2 (DM2), have been associated with chronic low-grade systemic
      inflammation. Elevated levels of interleukin-6 (IL-6), monocyte chemoattractant
      protein (MCP-1) and C-reactive protein (hs-CRP), are found in patients with type
      2 diabetes with and without complications. Angiotensin II (Ang II), a potent
      vasopressor, seems to regulate also the expression of the above inflammatory
      mediators acting as proinflammatory cytokine. In this study, we examined the
      effects of candesartan, an angiotensin receptror blocker, in the chronic low
      grade inflammation observed in DM 2. MATERIALS AND METHODS: Seventeen patients
      with DM2 of <5years duration were recruited for the study. Patients received 4mg
      of candesartan, an angiotensin receptor blocker, for 6months. Blood levels of IL
      6, MCP-1, hs-CRP and other inflammatory indices were measured before and at the
      end of candesartan administration. RESULTS: At the end of treatment with
      candesartan, IL-6 levels decreased significantly (P<0.05). Serum levels of MCP-1
      and hs-CRP showed a trend for significant decrease with treatment (P<0.08 and
      P<0.09, respectively). Statistically significant correlations were found between
      hs-CRP and MCP-1 (r=0.623, P< 0.05), IL-6 and MCP-1 (r=0.703, P<0.05) and TRT and
      MCP-1 (r=0.752, P<0.05), before but not at the end of candesartan administration.
      CONCLUSIONS: Candesartan could decrease the low-grade inflammation of type 2 DM
      as shown by the decrease of inflammatory mediators. Thus, angiotensin receptor
      blockers could be useful for treating patients with DM2 not only for their
      antihypertensive capacity but also for their anti-inflammatory actions.

PMID- 21175615
TI  - Cryo-electron tomography: methodology, developments and biological applications.
AB  - Cryo-electron tomography allows three-dimensional visualization of frozen
      hydrated, vitrified biological material at molecular resolution. Here, we
      summarize the most important sample preparation methods and technical aspects
      relevant for cryo-electron tomography, as well as its recent biological
      applications from isolated macromolecular complexes to entire cells and tissues.

PMID- 21175614
TI  - Variability in post-error behavioral adjustment is associated with functional
      abnormalities in the temporal cortex in children with ADHD.
AB  - BACKGROUND: Error processing is reflected, behaviorally, by slower reaction times
      (RT) on trials immediately following an error (post-error). Children with
      attention-deficit hyperactivity disorder (ADHD) fail to show RT slowing and
      demonstrate increased intra-subject variability (ISV) on post-error trials. The
      neural correlates of these behavioral deficits remain unclear. The dorsal
      anterior cingulate cortex (ACC) and lateral prefrontal cortex (PFC) are key
      regions implicated in error processing and subsequent behavioral adjustment. We
      hypothesized that children with ADHD, compared to typically developing (TD)
      controls, would exhibit reduced PFC activation during post-error (versus post
      correct inhibition) trials and reduced dACC activation during error (versus
      correct inhibition) trials. METHODS: Using functional Magnetic Resonance Imaging
      (fMRI) and a Go/No-Go task, we analyzed the neural correlates of error processing
      in 13 children with ADHD and 17 TD children. RESULTS: Behaviorally, children with
      ADHD showed similar RT slowing but increased ISV compared to controls. The post
      error contrast revealed a relative increase in blood-oxygen-level dependent
      (BOLD) signal in the middle/inferior temporal cortex (TempC), the
      ACC/supplementary motor area (SMA) and the somatosensory/auditory cortex (AudC)
      in children with ADHD compared to controls. Importantly, in the ADHD group,
      increased post-error temporal cortex activity was associated with lower ISV.
      During error (versus correct inhibition) trials, no between-group differences
      were detected. However, in children with ADHD lower ISV was associated with
      decreased insula and increased precentral gyrus activity. CONCLUSIONS: In
      children with ADHD, post-error neural activity suggests, first, a shift of
      attention towards task-irrelevant stimuli (AudC), and second, a recruitment of
      compensatory regions that resolve stimulus conflict (TempC) and improve response
      selection/execution (ACC/SMA). ADHD children with higher temporal cortex
      activation showed lower ISV, suggesting that functional abnormalities in the
      compensatory temporal regions contribute to increased variability. Moreover,
      increased ISV may be related to an over-sensitivity to negative outcomes during
      error trials in ADHD (insula correlation).

PMID- 21175616
TI  - NPY promotes chemokinesis and neurogenesis in the rat subventricular zone.
AB  - The subventricular zone (SVZ) is a major reservoir for stem cells in the adult
      mammalian brain. Neural stem cells supply the olfactory bulb with new
      interneurons and provide cells that migrate towards lesioned brain areas.
      Neuropeptide Y (NPY), one of the most abundant neuropeptides in the brain, was
      previously shown to induce neuroproliferation on mice SVZ cells. In the present
      study, performed in rats, we demonstrate the endogenous synthesis of NPY by cells
      in the SVZ that suggests that NPY could act as an autocrine/paracrine factor
      within the SVZ area. We observed that NPY promotes SVZ cell proliferation as
      previously reported in mice, but does not affect self-renewal of SVZ stem cells.
      Additionally, this study provides the first direct evidence of a chemokinetic
      activity of NPY on SVZ cells. Using pharmacological approaches, we demonstrate
      that both the mitogenic and chemokinetic properties of NPY involve Y1 receptor
      mediated activation of the ERK1/2 MAP kinase pathway. Altogether, our data
      establish that NPY through Y1 receptors activation controls chemokinetic activity
      and, as for mice, is a major neuroproliferative regulator of rat SVZ cells.

PMID- 21175617
TI  - Abnormal exocytotic release of glutamate in a mouse model of amyotrophic lateral
      sclerosis.
AB  - Glutamate-mediated excitotoxicity plays a major role in the degeneration of motor
      neurons in amyotrophic lateral sclerosis and reduced astrocytary glutamate
      transport, which in turn increases the synaptic availability of the amino acid
      neurotransmitter, was suggested as a cause. Alternatively, here we report our
      studies on the exocytotic release of glutamate as a possible source of excessive
      glutamate transmission. The basal glutamate efflux from spinal cord nerve
      terminals of mice-expressing human soluble superoxide dismutase (SOD1) with the
      G93A mutation [SOD1/G93A(+)], a transgenic model of amyotrophic lateral
      sclerosis, was elevated when compared with transgenic mice expressing the wild
      type human SOD1 or to non-transgenic controls. Exposure to 15 mM KCl or 0.3 MUM
      ionomycin provoked Ca(2+)-dependent glutamate release that was dramatically
      increased in late symptomatic and in pre-symptomatic SOD1/G93A(+) mice. Increased
      Ca(2+) levels were detected in SOD1/G93A(+) mouse spinal cord nerve terminals,
      accompanied by increased activation of Ca(2+)/calmodulin-dependent kinase II and
      increased phosphorylation of synapsin I. In line with these findings, release
      experiments suggested that the glutamate release augmentation involves the
      readily releasable pool of vesicles and a greater capability of these vesicles to
      fuse upon stimulation in SOD1/G93A(+) mice.

PMID- 21175618
TI  - Kindling alters neurosteroid-induced modulation of phasic and tonic GABAA
      receptor-mediated currents: role of phosphorylation.
AB  - We have previously shown that after kindling (a model of temporal lobe epilepsy),
      the neuroactive steroid tetrahydrodeoxycorticosterone (THDOC) was unable to
      augment GABA type A receptor (GABA(A))-mediated synaptic currents occurring on
      pyramidal cells of the piriform cortex. Phosphorylation of GABA(A) receptors has
      been shown previously to alter the activity of THDOC, so we tested the hypothesis
      that kindling induces changes in the phosphorylation of GABA(A) receptors and
      this accounts for the loss in efficacy. To assay whether GABA(A) receptors are
      more phosphorylated after kindling, we examined the phosphorylation state of the
      beta3 subunit and found that it was increased. Incubation of brain slices with
      the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) (100 nM)
      also increased phosphorylation in the same assay. In patch clamp, recordings from
      non-kindled rat brain slices PMA also reduced the activity of THDOC in a manner
      that was identical to what is observed after kindling. We also found that the
      tonic current was no longer augmented by THODC after kindling and PMA treatment.
      The protein kinase C (PKC) antagonist bisindolylmaleimide I blocked the effects
      PMA on the synaptic but not the tonic currents. However, the broad spectrum PKC
      antagonist staurosporine blocked the effects of PMA on the tonic currents,
      implying that different PKC isoforms phosphorylate GABA(A) receptors responsible
      for phasic and tonic currents. The phosphatase activator Li(+) palmitate restored
      the 'normal' activity of THDOC on synaptic currents in kindled brain slices but
      not the tonic currents. These data demonstrate that kindling enhances the
      phosphorylation state of GABA(A) receptors expressed in pyramidal neurons
      reducing THDOC efficacy.

PMID- 21175619
TI  - Understanding the pathogenesis of Alzheimer's disease: will RNA-Seq realize the
      promise of transcriptomics?
AB  - The prevalence of Alzheimer's disease (AD) is increasing rapidly in the western
      world and is poised to have a significant economic and societal impact. Current
      treatments do not alter the underlying disease processes meaning new treatments
      are required if this imminent epidemic is to be averted. The clinical
      manifestations of AD are secondary to a substantial loss of cortical neurons. To
      be effective, neuroprotective strategies will need to be implemented prior to
      this cell loss. However, this requires the discovery of both pre-clinical markers
      to identify susceptible patients and the early pathogenic mechanisms to serve as
      therapeutic targets. Although the biomarkers and pathogenic mechanisms may
      overlap, it is likely that new approaches are required to identify novel elements
      of the disease. Transcriptomic analyses, that assume no a priori etiological
      hypotheses, promise much in elucidating the pathogenesis of complex diseases like
      AD. Microarrays are the most popular platform for transcriptomic analysis and
      have been applied across AD models, patient samples and postmortem brain tissue.
      The results of these studies have been largely discordant which could, to some
      extent, reflect the limitations of this probe-hybridization-based methodology. In
      comparison, whole transcriptome sequencing (RNA-Seq) utilizes a highly efficient,
      next-generation DNA sequencing method with improved dynamic range and scope of
      transcript detection. RNA-Seq is not only highly suited to investigations of the
      genomically complex human brain tissue but it can potentially overcome technical
      issues inherent to case-control comparisons of postmortem brain tissue in
      neurodegenerative diseases. The volume of data generated by this platform looms
      as the major logistical hurdle and a systematic experimental approach will be
      required to maximise the detection of pathogenically relevant signals.
      Nevertheless, RNA-Seq looks set to deliver a quantum leap forward in our
      understanding of AD pathogenesis.

PMID- 21175621
TI  - What's another year?

PMID- 21175620
TI  - Lithium rescues the impaired autophagy process in CbCln3(Deltaex7/8/Deltaex7/8)
      cerebellar cells and reduces neuronal vulnerability to cell death via IMPase
      inhibition.
AB  - Juvenile neuronal ceroid lipofuscinosis (Batten disease) is a neurodegenerative
      disorder caused by mutation in CLN3. Defective autophagy and concomitant
      accumulation of autofluorescence enriched with mitochondrial ATP synthase subunit
      c were previously discovered in Cln3 mutant knock-in mice. In this study, we show
      that treatment with lithium reduces numbers of LC3-positive autophagosomes and
      accumulation of LC3-II in Cln3 mutant knock-in cerebellar cells
      (CbCln3(Deltaex7/8/Deltaex7/8) ). Lithium, an inhibitor of GSK3 and IMPase,
      reduces the accumulation of mitochondrial ATP synthase subunit c and
      autofluorescence in CbCln3(Deltaex7/8/Deltaex7/8) cells, and mitigates the
      abnormal subcellular distribution of acidic vesicles in the cells. L690,330, an
      IMPase inhibitor, is as effective as lithium in restoring autophagy in
      CbCln3(Deltaex7/8/Deltaex7/8) cells. Moreover, lithium or down-regulation of
      IMPase expression protects CbCln3(Deltaex7/8/Deltaex7/8) cells from cell death
      induced by amino acid deprivation. These results suggest that lithium overcomes
      the autophagic defect in CbCln3(Deltaex7/8/Deltaex7/8) cerebellar cells probably
      through IMPase, thereby reducing their vulnerability to cell death.

PMID- 21175622
TI  - A retrospective study of 153 cases of undiagnosed collapse, syncope or exercise
      intolerance: the outcomes.
AB  - OBJECTIVES: To retrospectively assess the long-term outcome for dogs that were
      presented with collapse, syncope or exercise intolerance for which an underlying
      cause is not identified. METHODS: The clinical records of animals presenting to
      two practices were assessed. Dogs which presented for collapse, syncope or
      exercise intolerance at least 6 months previously and did not receive a
      definitive diagnosis despite investigation were included. Follow-up of these
      cases was carried out by conducting telephone interviews with the owners.
      RESULTS: One hundred and fifty-three cases were successfully followed up.
      Clinical signs had resolved in 64 cases (42%), 35 dogs (23%) were continuing to
      exhibit clinical signs, although 22 of these had improved without medical
      intervention. In 17 cases (11%), a diagnosis had subsequently been made or
      treatment was being administered and 37 dogs (24%) had died. Of the deaths, 18
      (12%) were considered to be related to the original presentation. The overall
      prevalence of death and deterioration related to the problems investigated was
      16.2% of cases. Death in boxers was significantly more common than in other
      breeds (36%). CLINICAL SIGNIFICANCE: Death and deterioration are uncommon
      outcomes for dogs other than boxers presenting with collapse, syncope and
      exercise intolerance for which a definitive diagnosis cannot be made.

PMID- 21175623
TI  - Maxillomandibular external skeletal fixation in five cats with caudal jaw trauma.
AB  - Five cats with caudal jaw injuries including mandibular ramus fractures,
      temporomandibular luxation/subluxation and temporal bone fractures were managed
      with external skeletal fixation to provide open-mouth maxillomandibular fixation.
      Three of five cats were able to eat orally during the period of fixation, whereas
      two cats with jaws fixed in a suboptimal position were dependent on
      oesophagostomy tube nutrition. Fixation was well tolerated and was maintained for
      21 to 42 days. All cats were eating normally and had good jaw function at follow
      up (mean 39 months, range 7 to 71 months).

PMID- 21175624
TI  - Full recovery of subinvolution of placental sites in an American Staffordshire
      terrier bitch.
AB  - A three-year-old, sexually intact, female American Staffordshire terrier was
      presented with chronic postpartum vulvar haemorrhage. Sixty-one days before
      presentation, the bitch had whelped 10 puppies. A tentative diagnosis of
      subinvolution of placental sites was made when syncythial trophoblast-like cells
      were identified in the specimen collected through the opening of the cervix by
      endoscopy. Five weeks after the diagnosis, the bitch was clinically healthy with
      no vaginal bleeding and spontaneous recovery occurred without surgical treatment.

PMID- 21175625
TI  - Congestive heart failure in two pet rabbits.
AB  - This case report describes congestive heart failure with pleural effusion in two
      middle-aged, pet house rabbits. Both had a history of acute onset dyspnoea,
      weakness and weight loss. Bi-atrial enlargement was seen on echocardiography in
      both rabbits. One rabbit had atrial fibrillation and ventricular premature
      complexes identified on electrocardiography. There was a radiographically evident
      pleural effusion in both rabbits and thoracocentesis was undertaken in one
      rabbit. These findings were confirmed on post-mortem examination. The aetiology
      for the underlying heart disease was not found, but the potential types of
      cardiomyopathies are discussed.

PMID- 21175626
TI  - British Small Animal Veterinary Association Annual General Meeting, 11 April
      2010.

PMID- 21175629
TI  - A challenge for hyperaccumulating plant models: 'cycling' as fast as Arabidopsis
      thaliana.

PMID- 21175630
TI  - NO way to treat a cold.

PMID- 21175631
TI  - A new tool for functional genomics in maize.

PMID- 21175632
TI  - Plants and the Earth system - past events and future challenges.

PMID- 21175633
TI  - The cauliflower Orange gene enhances petiole elongation by suppressing expression
      of eukaryotic release factor 1.
AB  - The cauliflower (Brassica oleracea var. botrytis) Orange (Or) gene affects plant
      growth and development in addition to conferring beta-carotene accumulation. This
      study was undertaken to investigate the molecular basis for the effects of the Or
      gene mutation in on plant growth. The OR protein was found to interact with
      cauliflower and Arabidopsis eukaryotic release factor 1-2 (eRF1-2), a member of
      the eRF1 family, by yeast two-hybrid analysis and by bimolecular fluorescence
      complementation (BiFC) assay. Concomitantly, the Or mutant showed reduced
      expression of the BoeRF1 family genes. Transgenic cauliflower plants with
      suppressed expression of BoeRF1-2 and BoeRF1-3 were generated by RNA
      interference. Like the Or mutant, the BoeRF1 RNAi lines showed increased
      elongation of the leaf petiole. This long-petiole phenotype was largely caused by
      enhanced cell elongation, which resulted from increased cell length and elevated
      expression of genes involved in cell-wall loosening. These findings demonstrate
      that the cauliflower Or gene controls petiole elongation by suppressing the
      expression of eRF1 genes, and provide new insights into the molecular mechanism
      of leaf petiole regulation.

PMID- 21175634
TI  - Role of the plastidic glucose translocator in the export of starch degradation
      products from the chloroplasts in Arabidopsis thaliana.
AB  - In higher plants, the plastidic glucose translocator (pGlcT) is assumed to play a
      role in the export of starch degradation products, but this has not yet been
      studied in detail. To elucidate the role of pGlcT in the leaves of Arabidopsis
      thaliana, we generated single and double mutants lacking three plastidic sugar
      transporters, pGlcT, the triose-phosphate/phosphate translocator (TPT), and the
      maltose transporter (MEX1), and analyzed their growth phenotypes, photosynthetic
      properties and metabolite contents. In contrast to the pglct-1 and pglct-2 single
      mutants lacking a visible growth phenotype, the double mutants pglct-1/mex1 and
      tpt-2/mex1 displayed markedly inhibited plant growth. Notably, pglct-1/mex1
      exhibited more severe growth retardation than that seen for the other mutants. In
      parallel, the most severe reductions in sucrose content and starch turnover were
      observed in the pglct-1/mex1 mutant. The concurrent loss of pGlcT and MEX1 also
      resulted in severely reduced photosynthetic activities and extreme chloroplast
      abnormalities. These findings suggest that pGlcT, together with MEX1, contributes
      significantly to the export of starch degradation products from chloroplasts in
      A. thaliana leaves, and that this starch-mediated pathway for photoassimilate
      export via pGlcT and MEX1 is essential for the growth and development of A.
      thaliana.

PMID- 21175635
TI  - An elaborate heterotrimeric G-protein family from soybean expands the diversity
      of plant G-protein networks.
AB  - The repertoire of heterotrimeric G-proteins in plant species analyzed thus far is
      simple, with the presence of only two possible canonical heterotrimers in
      Arabidopsis and rice vs hundreds in animal systems. We assessed whether genome
      duplication events have resulted in the multiplicity of G-protein in plant
      species like soybean that would increase the complexity of G-protein networks. We
      identified and amplified four Galpha, four Gbeta and two Ggamma proteins,
      analyzed their expression profile by quantitative PCR during different
      developmental stages. We purified the four Galpha proteins and analyzed their
      guanosine-5'-triphosphate (GTP)-binding and GTPase activity. We performed yeast
      based interaction analysis to assess the interaction specificity of different G
      protein subunits. Our results show that all 10 G-protein genes are retained in
      the soybean genome and ubiquitously expressed. The four Galpha proteins seem to
      be plasma membrane-localized. The G-protein genes have interesting expression
      profiles during seed development and germination. The four Galpha proteins form
      two distinct groups based on their GTPase activity. Yeast-based interaction
      analyses predict that the proteins interact in most of the possible combinations,
      with some degree of interaction specificity between duplicated gene pairs. This
      research identifies the most elaborate heterotrimeric G-protein network known to
      date in the plant kingdom.

PMID- 21175636
TI  - The phosphoproteome of Arabidopsis plants lacking the oxidative signal-inducible1
      (OXI1) protein kinase.
AB  - The AGC protein kinase OXI1 is a key protein in plant responses to oxidative
      signals, and is important for two oxidative burst-mediated processes: basal
      resistance to microbial pathogens and root hair growth. To identify possible
      components of the OXI1 signalling pathway, phosphoproteomic techniques were used
      to detect alterations in the abundance of phosphorylated proteins and peptides in
      an oxi1 null mutant of Arabidopsis thaliana. The relative abundance of
      phosphorylated proteins was assessed either using two-dimensional gel
      electrophoresis and staining with the phosphoprotein stain Pro-Q Diamond or by
      the identification and quantification, by mass spectrometry, of stable-isotope
      labelled phosphopeptides. A number of proteins show altered phosphorylation in
      the oxi1 mutant. Five proteins, including a putative F-box and 3-phosphoinositide
      dependent kinase 1, show reduced phosphorylation in the oxi1 mutant, and may be
      direct or indirect targets of OXI1. Four proteins, including ethylene insensitive
      2 and phospholipase d-gamma, show increased phosphorylation in the oxi1 mutant.
      This study has identified a range of candidate proteins from the OXI1 signalling
      pathway. The diverse activities of these proteins, including protein degradation
      and hormone signalling, may suggest crosstalk between OXI1 and other signal
      transduction cascades.

PMID- 21175637
TI  - Dark-leaved willow (Salix myrsinifolia) is resistant to three-factor (elevated
      CO2, temperature and UV-B-radiation) climate change.
AB  - Elevated carbon dioxide (CO2 ), temperature (T) and ultraviolet-B (UV-B)
      radiation may affect plant growth and secondary chemistry in different
      directions, but the effect of the combination of the three factors has seldom
      been tested. Here, we grew four dark-leaved willow (Salix myrsinifolia) clones
      under combinations of ambient or elevated CO2, T and UV-B radiation in top-closed
      chambers for 7 wk. Elevated UV-B had no effects on growth or phenolic compounds,
      and there were no significant interactions between UV-B, CO2 and T. CO2 alone
      increased most growth parameters, but the magnitude of the effect varied among
      the clones. Total phenolics increased at elevated CO2 , whereas they decreased at
      elevated T. The responses varied between the clones. The results imply that dark
      leaved willow are fairly resistant to the applied three-factor climate change,
      probably because of high constitutive defense. However, the interactions between
      clone and climate change factors implies that some clones are more susceptible
      than the species as a whole.

PMID- 21175638
TI  - High sensitivity of Lobelia dortmanna to sediment oxygen depletion following
      organic enrichment.
AB  - * Lobelia dortmanna thrives in oligotrophic, softwater lakes thanks to O(2) and
      CO(2) exchange across roots and uptake of sediment nutrients. We hypothesize that
      low gas permeability of leaves constrains Lobelia to pristine habitats because
      plants go anoxic in the dark if O(2) vanishes from sediments. * We added organic
      matter to sediments and followed O(2) dynamics in plants and sediments using
      microelectrodes. To investigate plant stress, nutrient content and photosynthetic
      capacity of leaves were measured. * Small additions of organic matter triggered
      O(2) depletion and accumulation of NH(4)(+), Fe(2+) and CO(2) in sediments. O(2)
      in leaf lacunae fluctuated from above air saturation in the light to anoxia late
      in the dark in natural sediments, but organic enrichment prolonged anoxia because
      of higher O(2) consumption and restricted uptake from the water. Leaf N and P
      dropped below minimum thresholds for cell function in enriched sediments and was
      accompanied by critically low chlorophyll and photosynthesis. * We propose that
      anoxic stress restricts ATP formation and constrains transfer of nutrients to
      leaves. Brief anoxia in sediments and leaf lacunae late at night is a recurring
      summer phenomenon in Lobelia populations, but increased input of organic matter
      prolongs anoxia and reduces survival.

PMID- 21175639
TI  - Do tropical wetland plants possess convective gas flow mechanisms?
AB  - * Internal pressurization and convective gas flow, which can aerate wetland
      plants more efficiently than diffusion, are common in temperate species. Here, we
      present the first survey of convective flow in a range of tropical plants. * The
      occurrence of pressurization and convective flow was determined in 20 common
      wetland plants from the Mekong Delta in Vietnam. The diel variation in
      pressurization in culms and the convective flow and gas composition from stubbles
      were examined for Eleocharis dulcis, Phragmites vallatoria and Hymenachne
      acutigluma, and related to light, humidity and air temperature. * Nine of the 20
      species studied were able to build up a static pressure of > 50 Pa, and eight
      species had convective flow rates higher than 1 ml min(-1). There was a clear
      diel variation, with higher pressures and flows during the day than during the
      night, when pressures and flows were close to zero. * It is concluded that
      convective flow through shoots and rhizomes is a common mechanism for below
      ground aeration of tropical wetland plants and that plants with convective flow
      might have a competitive advantage for growth in deep water.

PMID- 21175640
TI  - Wind pollination over mesoscale distances: an investigation with Scots pine.
AB  - There is a gap between the order of magnitude of maximum documented distances of
      airborne tree pollen transport (up to 10(2)-10(3) km) and effective wind
      pollination (up to 10(1) km), which may partly derive from greater difficulties
      in detecting the latter. This study aims to assess wind pollination over scales
      closer to the maximum observed physical pollen transport distances. The origin of
      effective pollen immigrants into a strongly isolated Iberian Pinus sylvestris
      remnant was investigated using paternally inherited microsatellite markers and
      maximum-likelihood estimation combined with Monte Carlo assessment of parameter
      uncertainty. The results revealed significant effective pollen flow (up to 4.4%)
      from a large population located 100 km away, suggesting that the well-known
      mesoscale airborne transport of viable pine pollen can result in successful
      pollination over larger scales than previously reported for wind-pollinated tree
      species. This study supports the view that the gap between documented potential
      and effective wind pollen dispersal scales might not accurately reflect
      biological reality. Expanding the expected range of effective wind pollination
      has an impact on the assessment of a wide range of ecological and evolutionary
      processes, including reproductive assurance on fragmentation or colonization,
      metapopulation connectivity and interactions with local adaptation in
      heterogeneous habitats.

PMID- 21175641
TI  - The photodynamic therapy of cancer cells.

PMID- 21175642
TI  - Coumarins in Phormium (New Zealand flax) fibers: their role in fluorescence and
      photodegradation.
AB  - The genus Phormium (New Zealand flax) has fiber possessing a high content of
      lignin and, like other lignocellulosic materials, it is subject to
      photodegradation. Photoproducts in the fiber absorbing over a broad spectral
      region from ~370 to 600nm are observed as a result of exposure to near-UV
      radiation from 350 to 400 nm. Irradiation was shown to produce hydrogen peroxide
      and this can account, at least in part, for the photo-oxidation manifested in
      changes in the reflectance spectra of the fibers. Unirradiated solid fibers and
      their aqueous extracts exhibit fluorescence with excitation maxima at 350-360nm
      and emission maxima at 440 nm. The fluorescence spectra of the fibers change
      following exposure to near-UV radiation with the major fluorophore being
      substantially photodegraded, evidenced by a substantial loss of emission between
      410 and 480nm, which is largely responsible for the yellow and duller appearance
      of the fiber. Analysis of the aqueous extracts of the fibers, using electron
      spray ionization mass spectroscopy of aqueous extracts, showed the presence of
      coumarin, hydroxycoumarin and a number of substituted hydroxycoumarins. The
      spectral distributions of the fluorescence associated with the unirradiated
      fibers and their aqueous extracts are consistent with them originating from a
      number of 7-hydroxycoumarins present.

PMID- 21175643
TI  - Short exposure to the DNA intercalator DRAQ5 dislocates the transcription
      machinery and induces cell death.
AB  - The fluorescent probe DRAQ5 which rapidly permeates cells and binds to DNA is
      potentially useful for functional studies of molecular dynamics and interactions
      in living nuclei. Within minutes after the incubation of human osteosarcoma U2OS
      cells with 5MUm DRAQ5, the distributions of RNA polymerase II and some of its
      associated regulatory proteins HEXIM and cyclin T1 in the nucleus are severely
      impaired, and transcription is inhibited. Furthermore, 30min exposure to DRAQ5
      induces death of U2OS cells 24h later. Incubation with Hoechst 33342 under
      similar conditions does not induce these effects. These results emphasize the
      importance of carefully examining the functional consequences of labeling DNA
      with intercalating fluorescent dyes before use.

PMID- 21175644
TI  - Relationships of non-structural carbohydrates accumulation and translocation with
      yield formation in rice recombinant inbred lines under two nitrogen levels.
AB  - Stem non-structural carbohydrates (NSCs) and its relationship with yield
      formation was investigated under low nitrogen (LN) and normal nitrogen (NN)
      treatments, using 46 recombinant inbred lines from Zhenshan 97 * Minghui 63
      (Oryza sativa). Apparent contribution of transferred NSC to grain yield (AC(NSC)
      ) ranged from approximately 1 to 28% under LN and from 1 to 15% under NN.
      Concentration and total mass of NSC in stem (TM(NSC) ) at heading, apparent
      transferred mass of NSC (ATM(NSC) ) and AC(NSC) were larger under LN compared
      with NN. However, there was no significant difference in the apparent ratio of
      transferred NSC from stems to grain (AR(NSC) ). ATM(NSC) was positively
      correlated with grain yield, 1000-grain weight and AC(NSC) under both nitrogen
      levels, whereas AR(NSC) was highly correlated with harvest index and AC(NSC) .
      Leaf area contributed more strongly to grain yield compared with ATM(NSC) under
      both LN and NN. ATM(NSC) showed larger direct effects on grain yield under LN
      compared with NN. TM(NSC) at heading, small vascular bundles (SVBs) and spikelets
      per m(2) under LN had positive direct effects on ATM(NSC) . SVB and spikelets per
      m(2) under LN had larger and positive direct effects, and large vascular bundles
      had negative direct effects on AR(NSC) . TM(NSC) at heading and SVB under LN had
      positive direct effects on AC(NSC) . In brief, LN supply increased stem NSC
      accumulation and translocation to developing grain. Components of the source-sink
      flow system showed different effects on NSC translocation and contribution to
      yield formation, depending on genotype and nitrogen level.

PMID- 21175645
TI  - Lack of effect of unrefrigerated young whole blood transfusion on patient
      outcomes after massive transfusion in a civilian setting.
AB  - BACKGROUND: Warm fresh whole blood has been advocated for critical bleeding in
      the military setting. This study assessed whether unrefrigerated young whole
      blood transfusion, from donation to transfusion less than 24 hours, could reduce
      mortality of patients with critical bleeding in a civilian setting. STUDY DESIGN
      AND METHODS: A linked data cohort study was conducted on a total of 353
      consecutive patients requiring massive transfusion, defined as 10 units or more
      of red blood cells or whole blood transfusion within 24 hours, in a quaternary
      health care center in Australia. RESULTS: Of the 353 patients with massive blood
      transfusion in the study, 77 received unrefrigerated young whole blood
      transfusion (mean, 4.0 units; interquartile range, 2-6). The diagnosis, severity
      of acute illness, age, sex, and ABO blood group were not significantly different
      between the patients who received unrefrigerated young whole blood and those who
      did not. Unrefrigerated young whole blood transfusions were associated with a
      slightly improved coagulation profile (lowest fibrinogen concentrations 1.7g/L
      vs. 1.4g/L, p=0.006; worst international normalization ratio, 2.4 vs. 2.8,
      p=0.05) but did not reduce the total utilization of allogeneic blood products and
      subsequent use of recombinant Factor VIIa (27% vs. 22%, p=0.358). Thirty-day
      mortality and 8-year survival after hospital discharge (hazard ratio, 1.05; 95%
      confidence interval, 0.41-2.65; p=0.93) were also not different after the use of
      unrefrigerated young whole blood transfusion. CONCLUSIONS: Unrefrigerated young
      whole blood transfusion was not associated with a reduced mortality of patients
      requiring massive transfusion in a civilian setting when other blood products
      were readily available.

PMID- 21175647
TI  - Real-time polymerase chain reaction detection of parvovirus B19 DNA in blood
      donations using a commercial and an in-house assay.
AB  - BACKGROUND: European regulations require testing of manufacturing plasma for
      parvovirus B19 (B19) DNA to limit the load of this virus to a maximum acceptable
      level of 10 IU/uL. To meet this requirement, most manufacturers introduced a test
      algorithm to identify and eliminate high-load donations before making large
      manufacturing pools of plasma units. Sanquin screens all donations using a
      commercial assay from Roche and an in-house assay. STUDY DESIGN AND METHODS:
      Between 2006 and 2009, 6.2 million donations were screened using two different
      polymerase chain reaction (PCR) assays targeting B19 DNA. Donations with B19 DNA
      loads of greater than 1 * 10(6) IU/mL showing significant differences in viral
      load between the two assays were further analyzed by sequencing analysis.
      RESULTS: A total of 396 donations with B19 DNA loads of greater than 1 * 10(6)
      IU/mL were identified. Fifteen samples (3.8%) had discordant test results; 10
      samples (2.5%) were underquantified by the Roche assay, two samples (0.5%) were
      underquantified by the in-house assay, and three samples (0.8%) were not detected
      by the Roche assay. Sequencing analysis revealed mismatches in primer and probe
      binding regions. Phylogenetic analysis showed that 12 samples were B19 Genotype
      1. The three samples not detected by the Roche assay were B19 Genotype 2.
      CONCLUSION: This study shows that 3.8% of the viremic B19 DNA-positive donations
      are not quantified correctly by the Roche or in-house B19 DNA assays. B19
      Genotype 1 isolates showing incorrect test results are more common than B19
      Genotype 2 or 3 isolates. Newly designed B19 PCR assays for blood screening
      should preferably have multiplexed formats targeting multiple regions of the B19
      genome.

PMID- 21175646
TI  - The relationship between alloimmunization and posttransfusion granulocyte
      survival: experience in a chronic granulomatous disease cohort.
AB  - BACKGROUND: The efficacy of granulocyte transfusions in patients with HLA
      alloimmunization is uncertain. A flow cytometric assay using dihydrorhodamine 123
      (DHR), a marker for cellular NADPH oxidase activity, was used to monitor the
      differential survival of transfused oxidase-positive granulocytes in
      alloimmunized patients with chronic granulomatous disease (CGD). STUDY DESIGN AND
      METHODS: Ten patients with CGD and serious infections were treated with daily
      granulocyte transfusions derived from steroid and granulocyte-colony-stimulating
      factor-stimulated donors. The proportion of neutrophils with intact oxidase
      activity was quantitated by DHR fluorescence on samples drawn before and 1 hour
      after transfusion. The incidence of acute transfusion reactions was correlated
      with the results of DHR fluorescence and biweekly HLA serologic screening assays.
      RESULTS: Eight of 10 patients experienced acute adverse reactions in association
      with granulocyte transfusions. Four had only chills and/or fever, and four
      experienced respiratory compromise; all eight exhibited HLA alloimmunization.
      Mean (+/- SD) oxidase-positive cell recovery was 19.7 +/- 17.4% (n = 15
      transfusions) versus 0.95 +/- 1.59% (n = 16) in the absence and presence of HLA
      allosensitization, respectively (p < 0.01). Greater than 1% in vivo recovery of
      DHR-enhancing donor granulocytes was strongly correlated with lack of HLA
      alloimmunization. CONCLUSION: The ability to detect DHR-positive donor
      granulocytes by flow cytometry is strongly correlated with absence of HLA
      alloimmunization and lack of acute reactions to granulocyte transfusions in
      patients with CGD. If HLA antibodies are present and the survival of donor
      granulocytes is low by DHR analysis, transfusions should be discontinued,
      avoiding a therapy associated with high risk and unclear benefit.

PMID- 21175648
TI  - Transfusion-transmitted human immunodeficiency virus (HIV) from seroconverting
      donors is rare in England and Wales: results from HIV lookback, October 1995
      through December 2008.
AB  - BACKGROUND: Lookback is considered when human immunodeficiency virus (HIV) is
      detected in a repeat blood donor in case the immediately previous negative
      donation was donated in the infectious window period (IWP) or the assay(s)
      produced a false-negative result. HIV lookback investigations undertaken by NHS
      Blood and Transplant and the Welsh Blood Service between October 1995 and
      December 2008 are described. STUDY DESIGN AND METHODS: Investigations were
      undertaken into the previous negative donations of 113 HIV-infected donors,
      including retrospective testing of archive samples, tracing of components, and
      identification of recipients who were offered HIV testing when appropriate. Data
      were collated on HIV seroconverters and outcome of the lookback was summarized.
      RESULTS: Two previous negative donations given before the introduction of
      minipool nucleic acid testing (MP-NAT) screening were confirmed positive by
      individual retrospective polymerase chain reaction (PCR) testing of the archive
      specimen. Red blood cell components had been transfused from both donations. One
      recipient died after transfusion, and the other was alive and tested HIV
      positive. All 23 (20%) donations previously testing negative by MP-NAT were
      confirmed to be PCR negative on individual testing of an archive specimen and
      none of the tested recipients of these donations had evidence of transfusion
      transmitted HIV. CONCLUSION: The yield of lookback was low with one positive
      recipient identified over 13 years of surveillance: HIV transmission occurred
      from a window period donation given before the introduction of MP-NAT screening
      and would have been detected using current testing methods. Current residual risk
      estimates for the United Kingdom predict that HIV lookback will be of limited
      benefit, as demonstrated by our data.

PMID- 21175649
TI  - Hereditary hemochromatosis: patient experiences of the disease and phlebotomy
      treatment.
AB  - BACKGROUND: Hereditary hemochromatosis (HH) is a genetic disorder resulting in
      increased accumulation of dietary iron. It is associated with various clinical
      complications such as liver cirrhosis and diabetes. The aim of this study was to
      explore patients' experiences of living with HH, the diagnosis process, and
      phlebotomy treatment. STUDY DESIGN AND METHODS: An online survey was developed
      and completed by a total of 210 HH patients across the United States (n = 70),
      France (n = 50), Ireland (n = 40), and the United Kingdom (n = 50). RESULTS: Of
      the 210 patients, 30% were induction patients, 49% were maintenance patients, and
      22% had never received phlebotomy. The most common route to diagnosis was by
      chance (42%), although most patients (87%) reported experiencing symptoms they
      now associated with HH at the time of diagnosis. Fatigue (60%) and joint pain
      (50%) were the most frequently reported current symptoms. While 87% of patients
      felt that treatment with phlebotomy was "quite worthwhile" or "very worthwhile,"
      52% of induction patients and 37% of maintenance patients experienced side
      effects "always" or "most of the time" after phlebotomy and 16% of patients would
      "definitely" or "probably" decide not to receive phlebotomy if alternative
      options were available. CONCLUSION: Diagnosis of HH is likely made late in many
      patients and subsequent phlebotomy treatment, while considered worthwhile by
      most, leads to concerns over side effects and inconvenience, often impacting
      patients' lives. Greater efforts to promote awareness of the disease and reduce
      the treatment burden associated with phlebotomy are required to improve detection
      and management of this disease.

PMID- 21175653
TI  - A comparison of health care and blood supply system structures.
AB  - There is great diversity in the practice of blood banking and transfusion
      medicine between countries. We sought to relate this to the variety of health
      care and blood supply systems in different countries. Questionnaires were
      completed by respondents from 15 countries selected from among those with higher
      Human Development Indices. These data were reviewed searching for correlations
      with blood banking and transfusion medicine practices. Wide varieties of health
      care and blood supply schemes were documented. There was no apparent relationship
      between their structure and organization nor their financing arrangements and
      their proclivity for the implementation of new methods or approaches such as
      pathogen inactivation and universal leucoreduction. The costs of the operation of
      the blood supply system as represented by their product fees and the rate of
      collection of red cells could also not be associated with the factors examined.
      The diversity of practice evident across developed countries is not explicable
      solely through their health care and blood supply system structures. Other
      factors are likely involved but are not easy to define or measure.

PMID- 21175652
TI  - How much blood is needed?
AB  - Demographic changes in developed countries as their populations age lead to a
      steady increase in the consumption of standard blood components. Complex
      therapeutic procedures like haematopoietic stem cell transplantation,
      cardiovascular surgery and solid organ transplantation are options for an
      increasing proportion of older patients nowadays. This trend is likely to
      continue in coming years. On the other hand, novel aspects in transplant
      regimens, therapies for malignant diseases, surgical procedures and perioperative
      patient management have led to a moderate decrease in blood product consumption
      per individual procedure. The ageing of populations in developed countries, intra
      society changes in the attitude towards blood donation as an important altruistic
      behaviour and the overall alterations in our societies will lead to a decline in
      regular blood donations over the next decades in many developed countries.
      Artificial blood substitutes or in vitro stem cell-derived blood components might
      also become alternatives in the future. However, such substitutes are still in
      early stages of development and will therefore probably not alleviate this
      problem within the next few years. Taken together, a declining donation rate and
      an increase in the consumption of blood components require novel approaches on
      both sides of the blood supply chain. Different blood donor groups require
      specific approaches and, for example, inactive or deferred donors must be re
      activated. Optimal use of blood components requires even more attention.

PMID- 21175654
TI  - Red cell storage and prognosis.
AB  - During storage of red blood cells (RBC), these cells develop storage lesions. The
      clinical relevance of these storage lesions is heavily discussed in literature.
      In this review, different aspects of the storage lesion are shown and how these
      potentially affect posttransfusion performance of the RBC. An overview of the
      conflicting literature on the clinical relevance of prolonged storage is given,
      summarizing the evidence on associations with mortality, length of stay,
      (postoperative) infections and organ failure. Subsequently, possible explanations
      are given for the conflicting results in the clinical studies and suggestions on
      how to proceed.

PMID- 21175655
TI  - Transfusion practice and safety: current status and possibilities for
      improvement.
AB  - Audits of practice and incident reporting, most notably to national
      haemovigilance schemes, indicate that poor hospital transfusion practice is
      frequent and occasionally results in catastrophic consequences for patients.
      Improvements in practice are needed and depend on a combined approach including a
      better understanding of the causes of errors; a reduction in the complexity of
      routine procedures taking advantage of new technology systems, which enforce
      agreed guidelines and policies; the setting and regular monitoring of performance
      standards for key aspects of the hospital transfusion process, improved
      organisation of transfusion in hospitals and staff training; and further research
      on the safe and effective use of blood and alternatives to donor blood. There
      needs to be a greater recognition that 'transfusion safety' applies to the
      hospital transfusion process as well as the contents of blood bags and that
      resources need to be provided for the improvement of transfusion safety and
      management in hospitals commensurate to their importance.

PMID- 21175656
TI  - Haemovigilance: an effective tool for improving transfusion practice.
AB  - Haemovigilance is a tool to improve the quality of the blood transfusion chain,
      primarily focusing on safety. In this review we discuss the history and present
      state of this relatively new branch of transfusion medicine as well as some
      developments that we foresee in the near future. The top 10 results and
      conclusions are: (1) Haemovigilance systems have shown that blood transfusion is
      relatively safe compared with the use of medicinal drugs and that at least in
      Europe blood components have reached a high safety standard. (2) The majority of
      the serious adverse reactions and events occur in the hospital. (3) The majority
      of preventable adverse reactions are due to clerical errors. (4) Some adverse
      reactions such as anaphylactic reactions often are not avoidable and therefore
      have to be considered as an inherent risk of blood transfusion. (5) Well
      functioning haemovigilance systems have not only indicated how safety should be
      improved, but also documented the success of various measures. (6) The type of
      organisation of a haemovigilance system is of relative value, and different
      systems may have the same outcome. (7) International collaboration has been
      extremely useful. (8) Haemovigilance systems may be used for the vigilance and
      surveillance of alternatives for allogeneic blood transfusion such as cell
      savers. (9) Haemovigilance systems and officers may be used to improve the
      quality of aspects of blood transfusion other than safety, such as appropriate
      use. (10) Haemovigilance systems will be of benefit also for vigilance and
      surveillance of the treatment with other human products such as cells, tissues
      and organs.

PMID- 21175657
TI  - Recombinant plasma proteins.
AB  - For almost 50 years, the fractionation of human plasma has been the sole possible
      source of a wide range of therapeutic proteins--such as coagulation factors,
      anticoagulants, immunoglobulins, and albumin--essential to the treatment of
      serious congenital or acquired bleeding or immunological diseases. In the last 20
      years, the application of recombinant technologies to mammalian cell cultures has
      made possible--although with some limitations in productivity, costs, and
      immunogenic risks--to produce and commercialize complex plasma glycoproteins for
      human therapeutic applications and has opened the way to the development of new
      molecular entities. Today, the advanced exploration of alternative cell lines and
      enhanced cell culture systems, as well as the development of alternative
      expression technologies, such as transgenic animals, is opening a new era in the
      production of the full range of recombinant plasma protein therapeutics. In this
      review, we examine the achievements and ongoing challenges of the recombinant DNA
      technology as a platform for the production of plasma proteins and the advantages
      and limitations of such products compared to fractionated plasma proteins.

PMID- 21175658
TI  - Proteomic applications in blood transfusion: working the jigsaw puzzle.
AB  - The application of proteomic technologies to transfusion medicine has opened new
      avenues to our understanding of the products we prepare for patients and the
      processes that impact the quality of those products. The development of the field
      of proteomics has paralleled that of transfusion medicine with over a century of
      key scientific accomplishments required to bring us to our modern systems. We
      review the technology of proteomics and its application to transfusion medicine
      with specific reference to the analysis of blood products, both fractionated and
      fresh. Although the use of proteomic tools to address transfusion medicine
      questions is really just beginning, it is clear that this method of analysis
      provides different insights into unaddressed issues in the area of blood product
      research. Proteomics also offers the promise of improving our approach to the
      control of blood product quality and even the assessment of blood donors, but
      these are efforts for the near future.

PMID- 21175659
TI  - Hepatitis B, hepatitis C and HIV transfusion-transmitted infections in the 21st
      century.
AB  - In the past, transfusion-transmitted virus (TTV) infections were not uncommon. In
      recent years with advanced technologies and improved donor screening, the risk of
      viral transfusion transmission has been markedly reduced. Hepatitis B virus
      (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have all
      shown marked reduction in transmission rates. However, the newer technologies,
      including nucleic acid technology (NAT) testing, have affected the residual rates
      differently for these virally transmitted diseases. Zero risk, which has been the
      goal, has yet to be achieved. False negatives still persist, and transmissions of
      these viruses still occur, although rarely. It is known that HBV serological
      testing misses some infected units; likewise, HBV NAT-negative units have also
      been known to transmit the virus. Similarly, HIV minipool NAT-negative units have
      transmitted HIV, as recently as 2007; likely, these transmissions would have been
      prevented with single-unit NAT testing. Newer technologies, such as pathogen
      inactivation (PI), will (ideally) eliminate these falsely test negative
      components, regardless of the original testing method used for detecting the
      viruses.

PMID- 21175660
TI  - Plasmodium falciparum malaria and the immunogenetics of ABO, HLA, and CD36
      (platelet glycoprotein IV).
AB  - Plasmodium falciparum malaria has long been a killer of the young, and has
      selected for polymorphisms affecting not only erythrocytes, but the
      immunogenetics of three histocompatibility systems: ABO, human leukocyte antigen
      (HLA), and CD36. The ABO system is important because the original allele,
      encoding glycosylation with the A sugar, acts as an adhesion ligand with infected
      red blood cells (iRBC), thereby promoting vasoocclusion. The prevalence of blood
      group O, which reduces this cytoadhesion, has increased in endemic areas. Other
      adaptations which could mitigate A-mediated rosetting include weaker A expression
      and increased soluble A secretion. The role of the HLA system in malaria has been
      harder to verify. Although HLA-B53 and DRB1*04 may be associated with clinical
      outcome, HLA studies are challenged by numerous comparisons in this most
      polymorphic of systems, and confounded by increasingly heterogeneous populations.
      Certain HLA markers may also reflect linkage artefact with other malaria-relevant
      polymorphisms. HLA may be less important because the parasite predominantly
      invades a compartment which does not express HLA. Adhesion of iRBCs is also
      mediated by CD36, expressed on platelets, monocytes, and microvascular
      endothelium. CD36 on monocytes is involved in clearing iRBC, while CD36 on
      platelets and the endothelium may play a role in tissue sequestration. The
      genetics of CD36 expression are complex, and recent research is fraught with
      inconsistent results. The solution may lie in examining genotype-phenotype
      correlations, zygosity effects on differential tissue expression, or other
      mechanisms altering CD36 tissue expression. Carefully designed prospective
      studies should bridge the gap between in-vitro observations and clinical
      outcomes.

PMID- 21175661
TI  - Developing pathogen reduction technologies for RBC suspensions.
AB  - Numerous studies have evaluated a wide variety of photosensitizers and alkylating
      agents as candidates for a pathogen reduction process to be used in RBC
      suspensions. The methodologies that produce robust inactivation of pathogens with
      maintenance of RBC properties during storage involve those that specifically
      target nucleic acids. This has been demonstrated through in vitro studies by
      flexible photosensitizers, which specifically target nucleic acid but do not
      engage in photochemistry when free in solution and nucleic acid alkylating agents
      in conjunction with extracellular quencher(s) to protect against RBC membrane
      alkylation. The flexible photosensitizer method must be scaled up to entire
      units, and toxicology studies would need to be performed for further development.
      Clinical trials will ultimately be necessary to further develop either flexible
      photosensitizers or nucleic acid alkylating methods with quenchers for use in
      Transfusion Medicine.

PMID- 21175662
TI  - Antibody-mediated (immune) transfusion-related acute lung injury.
AB  - Antibody-mediated transfusion-related acute lung injury (immune TRALI) is now
      recognized as the most common cause of transfusion-associated major morbidity and
      death in the Western world. Among the implicated leucocyte antibodies, these ones
      directed against the human leucocyte antigens (HLA) class II, human neutrophil
      alloantigens (HNA)-3a and HLA-A2 antigens are frequently associated with severe
      (artificial ventilation required) and fatal cases. There is accumulating evidence
      that preventive measures such as transfusion of plasma-rich blood components from
      male donors or from donors tested negative for leucocyte antibodies are effective
      in the reduction of severe and fatal immune TRALI.

PMID- 21175663
TI  - Structural modelling of red cell surface proteins.
AB  - The red cell surface membranes contain a large variety of proteins, many of which
      express blood group activity as a result of variation in their oligosaccharide or
      amino acid sequences. To understand the nature of the blood group epitopes, the
      functions of the proteins that express them and their relationship to each other,
      computer modelling has been employed to provide predictions of their structures.
      Modelling is an excellent method of first resort when experimental structural
      data for the protein of interest are absent or incomplete. The model can then be
      used to explain previous experimental data and to direct future experiments. In
      this review, examples of protein modelling are taken from the Rh, RHAG, Kell, LW,
      Lutheran, Duffy, Dombrock and RAPH blood group systems.

PMID- 21175664
TI  - The functional importance of blood group-active molecules in human red blood
      cells.
AB  - Antigens of 23 of the 30 human blood group systems are defined by the amino acid
      sequence of red cell membrane proteins. The antigens of DI, RH, RHAG, MNS, GE and
      CO systems are carried on blood group-active proteins (Band 3, D and CE
      polypeptides, RhAG, Glycophorins A and B, Glycophorins C and D and Aquaporin 1,
      respectively) which are expressed at high levels (>200,000 copies/red cell).
      These major proteins contribute to essential red cell functions either directly
      as membrane transporters and by providing linkage to the underlying red cell
      skeleton or by facilitating the membrane assembly of the protein complexes
      involved in these processes. The proteins expressing antigens of the remaining 17
      blood group systems are much less abundant (<20,000 copies/red cell) and their
      functional importance for the circulating red cell is largely unknown. Human gene
      knock-outs (null phenotypes) have been described for many of these minor blood
      group-active proteins, but only absence of Kx glycoprotein has been clearly
      linked with pathology directly related to the function of circulating red cells.
      Recent evidence suggesting the normal quality control system for glycoprotein
      synthesis is altered during the latter stages of red cell production raises the
      possibility that many of these low abundance blood group-active proteins are
      vestigial. In sickle cell disease and polycythaemia vera, elevated Lutheran
      glycoprotein expression may contribute to pathology. Dyserythropoiesis with
      reduced antigen expression can result from mutations in the erythroid
      transcription factors GATA-1 and EKLF.

PMID- 21175665
TI  - Umbilical cord blood: current status and future directions.
AB  - Once considered biological waste, umbilical cord blood (UCB) has become an
      accepted source of haematopoietic stem cells (HSCs). With initial success in the
      pediatric setting, UCB transplantation continues to gain favor in the adult
      patient population. Novel approaches to UCB transplantation include use of two
      units and a variety of graft manipulations. Additional uses for UCB are currently
      being explored and include applications in regenerative medicine and
      immunotherapy.

PMID- 21175666
TI  - HLA, immunogenetics, pharmacogenetics and personalized medicine.
AB  - Displaying the highest level of diversity of any functional genetic complex with
      medical impact, the HLA system represents a landmark and a model for the
      development of predictive and preventive medicine. The massive amount of data
      which will soon be obtained through new high through put technologies for
      individual genomes and transcriptomes challenges the HLA and medicine paradigm.
      Systems biology approach and integrative methodologies will undoubtedly be needed
      to unravel the ever growing number of HLA and diseases associations and the role
      of immunogenetics in transplantation and other allogeneic cell therapies. Also
      HLA, immunogenetics and pharmacogenetics are merging to bring to the individual
      patient tailored and personalized treatment. Providing insights into the
      complexities of predictive, preventive participatory and personalized medicine,
      the role of the HLA system will be consolidated at the forefront of the newer
      medicine.

PMID- 21175667
TI  - The influence of extracellular matrix proteins and mesenchymal stem cells on
      erythropoietic cell maturation.
AB  - BACKGROUND AND OBJECTIVES: As part of the bone marrow niche, cellular and
      acellular components like mesenchymal stem cells (MSCs) and extracellular matrix
      (ECM) proteins influence human haematopoiesis. To identify factors able to
      improve the in vitro generation of red blood cells (RBCs), we investigated the
      effect of these factors on proliferation and differentiation of human
      haematopoietic stem cells (HSCs) into erythroid cells. MATERIAL AND METHODS:
      Granulocyte colony-stimulating factor-mobilized CD34(+) HSCs were cultured for 16
      days using an in vitro erythropoiesis assay as described previously (by our
      group). The HSCs were co-cultured with MSCs in either direct or indirect contact
      and with different ECM proteins (fibronectin, laminin, collagen and a mixture of
      ECM proteins, called ECM gel). RESULTS: Co-culturing of HSCs with ECM gel
      improved cell viability, and the presence of laminin slightly increased the
      maturation into enucleated RBCs. HSC expansion could not be improved by addition
      of any of the ECM proteins investigated. In contrast, fibronectin inhibited
      erythroid formation. Co-culturing of HSCs with MSCs generally stimulated cell
      viability and HSC proliferation, however, in favour of the myeloid lineage. In
      summary, of all investigated factors, only laminin and ECM gel had a supportive
      effect on RBC development under the described in vitro culture conditions.

PMID- 21175669
TI  - Characteristics of prion-filtered red cells suspended in pathogen-inactivated
      plasma (MB treated or solvent-detergent treated) for neonatal exchange
      transfusion.
AB  - BACKGROUND AND OBJECTIVES: Neonates undergoing exchange transfusion require <5
      day-old red cells suspended in plasma. This study assesses the effect of
      replacing the saline, adenine, glucose and mannitol (SAGM) of prion reduced (P
      Capt) red cells with either methylene blue-treated plasma (MBTFFP) or OctaplasLG
      to reduce the risk of variant Creutzfelt-Jakob disease transmission. MATERIALS
      AND METHODS: Twenty leucoreduced red cell units in SAGM were prion reduced on day
      1. The SAGM was replaced by MBTFFP (n=10) or OctaplasLG (n=10). The units were
      irradiated and stored at 4 degrees C for 24 h. A further 20 units were stored for
      5 days before being processed as above. Haemolysis (%), potassium, ATP, 2,3-DPG
      and plasma proteins were measured. RESULTS: Haemolysis remained low (<=0.16%).
      Following irradiation and storage, red cells in both types of plasma showed
      similar changes in potassium and ATP concentrations. The 2,3-DPG concentrations
      were well maintained although lower in red cells in OctaplasLG compared with
      those in MBTFFP (4.79 vs. 6.83 MUmoles/g Hb on day 6). MBTFFP contained lower
      concentrations of fibrinogen, FV and FVIII. In OctaplasLG, alpha-2-antiplasmin
      was approximately 0.4 U/ml lower than in MBTFFP. After 24 h at 4 degrees C, free
      protein S in OctaplasLG fell from 0.82 to 0.57 IU/ml. Other plasma proteins, in
      both types of plasma, were stable. CONCLUSIONS: Red cells in both types of plasma
      demonstrated similar storage characteristics. The plasma proteins, except protein
      S in OctaplasLG, were stable over 24 h at 4 degrees C in both types of plasma,
      and low FVIII concentrations were noted in the MBTFFP (group O) units used.

PMID- 21175668
TI  - In vitro effects on platelets irradiated with short-wave ultraviolet light
      without any additional photoactive reagent using the THERAFLEX UV-Platelets
      method.
AB  - BACKGROUND: A novel short-wave ultraviolet light (UVC) pathogen reduction
      technology (THERAFLEX UV-Platelets; MacoPharma, Mouvaux, France) without the need
      of any additional photoactive reagent has recently been evaluated for various
      bacteria and virus infectivity assays. The use of UVC alone has on the one hand
      been shown to reduce pathogens but may, on the other hand, have some impact on
      the platelet (PLT) quality. The purpose of this study was to determine the
      potential effects on PLT quality of pathogen inactivation treatment using the
      novel UVC method for PLT concentrates. STUDY DESIGN AND METHODS: Buffy-coat
      derived PLTs suspended in SSP+ were irradiated with UVC light in plastic bags
      (MacoPharma) made of ethyl vinyl acetate, considered to be highly permeable to
      UVC light. The UVC-treated (test, n=8) as well as the untreated (reference, n=8)
      PLT units were stored in PLT storage bags composed of n-butyryl, tri n-hexyl
      citrate-plasticized polyvinyl chloride (MacoPharma) on a flat bed agitator for in
      vitro testing during 7 days of storage. RESULTS: No significant difference in PLT
      counts and lactate dehydrogenase between the groups was detected. During storage,
      glucose decreased more and lactate increased more in the test units.
      Statistically significant differences were found for glucose (P<0.01) and lactate
      (P<0.05) on day 7. ATP levels were higher (P<0.01 from day 5) in the reference
      units. With exception of day 7 (P<0.01 reference vs. test), hypotonic shock
      response reactivity was not different between groups. Extent of shape change was
      lower (P<0.01), and CD62P (P<0.05 day 5) was higher in the test units. CD42b and
      CD41/61 showed similar trends throughout storage, without any significant
      difference between the units. pH was maintained at >6.8 (day 7) and swirling
      remained at the highest level (score = 2) for all units throughout storage.
      CONCLUSION: Our results suggest that irradiation with UVC light has a slight
      impact on PLT in vitro quality and appears to be insignificant with regard to
      current in vitro standards.

PMID- 21175670
TI  - Effect of rate and delay of cooling during initial cooling process: in vitro
      effect on red cells.
AB  - BACKGROUND: Whole blood is stored at room temperature (RT) until processing into
      components. After separation and filtration, the RCC has to be cooled from RT to
      +2 - 6 degrees C. Different start times of the cooling process and different
      cooling rates can be encountered in daily routine. The effect of these parameters
      of the initial cooling of leucoreduced red cell concentrates (LR-RCC) on in vitro
      quality is not known. METHODS: In paired experiments (n=12), LR-RCCs in SAGM were
      cooled immediately after preparation from RT to +2 to +6 degrees C either 'fast'
      (within 21/2 h) or 'slow' (within 10-24 h) or 'slow' after a holding period of 6,
      12, 18 or 24 h. Units were then stored at +2-6 degrees C for 42 days and sampled
      at regular intervals for in vitro analysis. RESULTS: Irrespective of the start
      time and cooling rate during the initial cooling process, all units maintained
      good in vitro quality up to Day 42 with haemolysis <0.8%. Adenosine triphosphate
      (ATP) levels remained >2.7 MUmol/g Hb in 99% of all units up to Day 35.
      Differences in pH, ATP content and 2,3-DPG content between the groups were
      largest at Day 2 or 3 but generally disappeared during storage. CONCLUSION: Start
      time and cooling rate of the initial cooling process had minor effects on in
      vitro quality of red cells. LR-RCCs can be stored up to 24 h before cooling down
      to +2-6 degrees C without deleterious effects on in vitro parameters during 42
      day storage.

PMID- 21175672
TI  - Paranoid induction reduces N400s of healthy subjects with delusional-like
      ideation.
AB  - A previous study suggests that the amplitude of the N400 event-related potentials
      (ERPs) of healthy subjects does not vary with their delusional-like ideations.
      This contrasts with the smaller N400 amplitudes observed in more- than in less
      deluded schizophrenia patients. Here, we hypothesize that these smaller N400
      amplitudes were related to the paranoid feelings patients had during the ERP
      recording. We thus induced this type of feelings in healthy subjects. Delusional
      like ideation was assessed with the schizotypal personality questionnaire. Thirty
      four healthy subjects completed a semantic categorization task. Paranoid feelings
      were significantly enhanced by the induction. In these conditions, greater
      delusional-like ideation scores were associated with smaller N400 amplitudes and
      larger late positive components. Controlling for the two other schizotypal
      factors strengthened these results. These findings may help us understand why
      delusions persist.

PMID- 21175671
TI  - Differential age effects on lexical ambiguity resolution mechanisms.
AB  - Multiple neurocognitive subsystems are involved in resolving lexical ambiguity
      under different circumstances. We examined how processing in these subsystems
      changes with normal aging by comparing ERP responses to homographs and
      unambiguous words completing congruent sentences (with both semantic and
      syntactic contextual information) or syntactic prose (syntactic information
      only). Like young adults in prior work, older adults elicited more negative N400s
      to homographs in congruent sentences, suggesting mismatch between the context and
      residual activation of the contextually irrelevant sense. However, the frontal
      negativity seen in young adults to homographs in syntactically well-defined but
      semantically neutral contexts was absent in older adults as a group, suggesting a
      decline in recruiting additional neural resources to aid difficult semantic
      selection. A subset of older adults with high verbal fluency maintained a young
      like effect pattern.

PMID- 21175673
TI  - Failing where others have succeeded: Medial Frontal Negativity tracks failure in
      a social context.
AB  - Most of us can appreciate that it feels worse to fail when people around you are
      successful than when others are also failing. Indeed, comparison with other
      individuals is of central importance within social groups. Despite the importance
      of relative success or failure for human decision making and even well-being, the
      underlying neurobiological substrate of this social comparison process is not
      well understood. In the present study, ERPs were recorded while two participants
      received feedback on both their own, and the other participant's performance on
      each trial. The results showed that medial frontal negativity, an ERP component
      associated with deviations from the desired outcome, is particularly enhanced
      when an individual's own outcomes are worse than those of others. These results
      indicate that the way the brain evaluates the success of our actions is crucially
      dependent on the success or failure of others.

PMID- 21175674
TI  - The coming of age of antibiotics: discovery and therapeutic value.
AB  - Origins of antibiotic drug discovery are frequently traced to 1929 when Alexander
      Fleming recognized the antibacterial activity of a substance secreted by
      Penicillium notatum on a contaminated culture plate. However, the subsequent
      development of penicillin as a therapeutic agent was not realized until the early
      1940s, after a consortium of academic and pharmaceutical scientists from England
      and the United States developed sufficiently advanced fermentation technology to
      produce high-purity penicillin in large enough quantities for medical supplies.
      It was at this time that the antibiotic era was truly successfully launched.
      During the following decade, unprecedented antibiotic research and development
      emerged in academic laboratories and the pharmaceutical industry, resulting in
      identification of most of the antibiotic classes currently used therapeutically.
      This short historical commentary describes some of these early events, beginning
      with a conference held at the New York Academy of Sciences in 1946, the first
      conference to focus entirely on the latest science related to the identification
      and characterization of antibacterial substances produced by microorganisms.

PMID- 21175675
TI  - Structure-based design of anti-infectives.
AB  - Infectious diseases, caused by bacteria, viruses, fungi, protozoa, or parasites
      are among the leading causes of death worldwide. The efficacy of all current anti
      infectives is threatened by the spread of drug resistance factors, with some
      already made ineffective, and, as a result, there is a pressing need for a new
      pipeline of robust anti-infective drugs. In silico approaches, such as virtual
      high throughput screening and de novo structure-based rational drug design, have
      been established as powerful tools in drug discovery. In this review, we explore
      the exciting opportunities for antimalarial, antiviral, and antibacterial drug
      discovery arising from the new paradigm of structure-based drug design.

PMID- 21175676
TI  - Clostridium difficile: progress and challenges.
AB  - There is a surge of new interest in C. difficile infection (CDI) reflecting
      substantial increases in cases and fatalities. The new challenges by this now old
      pathogen have brought renewed interest in all facets of the disease. Particularly
      important are the role of fluoroquinolones as inducing agents, the new polymerase
      chain reaction test to detect toxigenic strains in stools, the important role of
      the NAP-1 strain, recent evidence favoring oral vancomycin over metronidazole in
      seriously ill patients, and new guidelines for management.

PMID- 21175677
TI  - Antibiotic heterogeneity: from concept to practice.
AB  - Bacterial resistance to multiple antibiotics is a serious and emerging threat.
      Several measures have been proposed to curb this growing trend. These include
      prescribing restrictions, education, and infection control that target
      transmission, among several others. Antibiotic cycling has been a subject of
      debate, and although many investigators have studied the utility of antibiotic
      cycling with the help of theoretical models or as part of clinical
      investigations, several areas remain undefined and unclear. This review
      summarizes the available information on antibiotic heterogeneity (antibiotic
      cycling, antibiotic mixing, and other types of antibiotic protocols) with a
      critical analysis of the published studies.

PMID- 21175679
TI  - Antibiotic substances-contribution of the microbiologist.

PMID- 21175680
TI  - Production of antibiotic substances by actinomycetes.

PMID- 21175681
TI  - Antibiotic substances produced by bacteria.

PMID- 21175682
TI  - The role played by natural selection on Mendelian traits in humans.
AB  - Detecting whether and how natural selection has targeted regions of the human
      genome represents a complementary strategy for identifying functionally important
      loci and variants involved in disease resistance and adaptation to the
      environment. In contrast with most complex diseases or traits, the genetic
      architecture of most Mendelian traits is relatively well established. Most
      mutations associated with Mendelian disease-related traits are highly penetrant
      and kept at low population frequencies because of the effects of purifying
      selection. However, this is not always the case. Here, we review several examples
      of Mendelian mutations-associated with various disease conditions or other traits
      of anthropological interest-that have increased in frequency in the human
      population as a result of past positive selection. These examples clearly
      illustrate the value of a population genetics approach to unravel the biological
      mechanisms that have been central to our past and present survival against the
      selective pressures imposed by diseases and other environmental factors.

PMID- 21175683
TI  - Disruption of long-distance highly conserved noncoding elements in
      neurocristopathies.
AB  - One of the key discoveries of vertebrate genome sequencing projects has been the
      identification of highly conserved noncoding elements (CNEs). Some
      characteristics of CNEs include their high frequency in mammalian genomes, their
      potential regulatory role in gene expression, and their enrichment in gene
      deserts nearby master developmental genes. The abnormal development of neural
      crest cells (NCCs) leads to a broad spectrum of congenital malformation(s),
      termed neurocristopathies, and/or tumor predisposition. Here we review recent
      findings that disruptions of CNEs, within or at long distance from the coding
      sequences of key genes involved in NCC development, result in neurocristopathies
      via the alteration of tissue- or stage-specific long-distance regulation of gene
      expression. While most studies on human genetic disorders have focused on protein
      coding sequences, these examples suggest that investigation of genomic
      alterations of CNEs will provide a broader understanding of the molecular
      etiology of both rare and common human congenital malformations.

PMID- 21175684
TI  - Modifier genes in Mendelian disorders: the example of cystic fibrosis.
AB  - In the past three decades, scientists have had immense success in identifying
      genes and their variants that contribute to an array of diseases. While the
      identification of such genetic variants has informed our knowledge of the
      etiologic bases of diseases, there continues to be a substantial gap in our
      understanding of the factors that modify disease severity. Monogenic diseases
      provide an opportunity to identify modifiers as they have uniform etiology,
      detailed phenotyping of affected individuals, and familial clustering. Cystic
      fibrosis (CF) is among the more common life-shortening recessive disorders that
      displays wide variability in clinical features and survival. Considerable
      progress has been made in elucidating the contribution of genetic and nongenetic
      factors to CF. Allelic variation in CFTR, the gene responsible for CF, correlates
      with some aspects of the disease. However, lung function, neonatal intestinal
      obstruction, diabetes, and anthropometry display strong genetic control
      independent of CFTR, and candidate gene studies have revealed genetic modifiers
      underlying these traits. The application of genome-wide techniques holds great
      promise for the identification of novel genetic variants responsible for the
      heritable features and complications of CF. Since the genetic modifiers are known
      to alter the course of disease, their protein products become immediate targets
      for therapeutic intervention.

PMID- 21175685
TI  - Hearing loss: a common disorder caused by many rare alleles.
AB  - Perception of sound is a fundamental role of the auditory system. Traveling with
      the force of their mechanical energy, sound waves are captured by the ear and
      activate the sensory pathway of this complex organ. The hair cells, specialized
      sensory cells within the inner ear, transmit the mechanical energy into
      electrical nerve stimuli that reach the brain. A large number of proteins are
      responsible for the overarching tasks required to maintain the complex mechanism
      of sound sensation. Many hearing disorders are due to single gene defects
      inherited in a Mendelian fashion, thus enabling clinical diagnostics. However, at
      the same time, hearing impairment is genetically heterogeneous, with both common
      and rare forms occurring due to mutations in over 100 genes. The crosstalk
      between human and mouse genetics has enabled comprehensive studies on gene
      identification and protein function, taking advantage of the tools animal models
      have to offer. The aim of the following review is to provide background and
      examples of human deafness genes and the discovery of their function in the
      auditory system.

PMID- 21175687
TI  - Congenital disorders of glycosylation.
AB  - Congenital (genetic) disorders of glycosylation (CDG) are a rapidly growing
      disease family, with some 45 members reported since its first clinical
      description in 1980. Most of these are protein hypoglycosylation diseases, but
      recently three defects in lipid glycosylation have been identified. Most protein
      hypoglycosylation diseases are due to defects in the N-glycosylation pathway (16
      diseases). The remaining ones affect the O-glycosylation pathway (8 diseases),
      both the N- and the O-glycosylation pathways, or other pathways (17 diseases).
      CDG can affect nearly all organs and systems, but there is often an important
      neurological component. The first-line screening for the N-glycosylation diseases
      is serum transferrin isoelectrofocusing (IEF), and for the O-glycosylation
      disorders apo CIII IEF. It has to be stressed that a normal test result does by
      no means exclude a CDG. In case of an abnormal result and as long as the basic
      defect has not been elucidated, the disease is labeled CDG-x (CDG-Ix when the
      transferrin IEF shows a type 1 pattern, and CDG-IIx when it shows a type 2
      pattern).

PMID- 21175686
TI  - Investigation of Mendelian forms of obesity holds out the prospect of
      personalized medicine.
AB  - Mendelian forms of obesity are already known to account for approximately 5% of
      the severely obese but are currently underinvestigated. In contrast, there has
      been much recent concentration on genome-wide single nucleotide polymorphism
      (SNP) associations in obesity, with particular emphasis given to the role of the
      fat mass and obesity associated (FTO) gene. Unfortunately, despite the enormous
      resources devoted to this work, none of the SNP markers in the ~30 genes
      discovered to have associations with common obesity have meaningful predictive
      power. This is very different from the situation for Mendelian obesity, where
      mutations have very clear effects on phenotype. Study of Mendelian obesity has
      also added significantly to our understanding of mechanisms of appetite
      regulation, with all known causative genes being active in the brain and most
      forming part of the leptin-melanocortin signaling pathway. Investigation of
      genomic structural variation has also recently revealed deletions causing
      obesity, sometimes with concomitant neurocognitive dysfunction. Advances in next
      generation sequencing are expected to uncover additional highly penetrant causes
      of obesity. Screening for Mendelian forms of obesity is rarely carried out but
      holds considerable promise for improved clinical care of these high-risk
      patients.

PMID- 21175688
TI  - Digital sheath synovial ganglion cysts in horses.
AB  - OBJECTIVES: To report the clinical features of horses with fluid-filled masses
      associated with the digital flexor tendon sheath (DFTS) and outcome after
      surgery. STUDY DESIGN: Case series. ANIMALS: Horses (n=10) METHODS: Medical
      records of horses with fluid-filled masses associated with the DFTS were reviewed
      and the clinical features, diagnostic methods, treatment, histopathology, and
      outcome reported. RESULTS: Masses were unilateral (7 hind limb, 3 front limb) and
      in 8 horses were associated with lameness. In 6 horses, lameness improved by >50%
      with intrathecal DTFS anesthesia, whereas 2 were less positive but were further
      improved with perineural anesthesia just proximal to the cyst. Communication
      between the DFTS and mass was identified in all horses ultrasonographically.
      Resection of the mass resolved lameness in 7 horses. Histologically (5
      specimens), the mass was characterized by a fibrous outer layer without a
      synovial lining, consistent with a ganglion cyst. CONCLUSION: The histologic
      appearance of ganglion cysts suggests that they arise from trauma to the sheath
      wall and may subsequently be a cause of lameness.

PMID- 21175689
TI  - Comparison of fixation methods for treatment of long bone fractures in llamas and
      alpacas.
AB  - OBJECTIVE: To determine outcome after repair of long bone fractures in llamas and
      alpacas. STUDY DESIGN: Case series. ANIMALS: Llamas (n=11) and alpacas (8).
      METHODS: Medical records (1998-2008) of camelids with long bone fractures were
      reviewed for history, repair method, and complications. Outcome was also assessed
      by owner telephone questionnaire. RESULTS: Mean age at repair was 39 months.
      There were 8 males and 11 females. Fracture distribution was tibia (n=6),
      metatarsus (5), metacarpus (4), radius and ulna (2), humerus (1), and femur (1),
      with 13 closed and 6 open fractures. Fracture repair was by internal fixation
      (n=11), external fixation with a transfixation pin cast (5), external coaptation
      (2), and cross-pinning (1). In 1 llama, the limb was amputated to revise a failed
      external fixation repair. Seventeen animals (89%) were discharged, and 2 were
      euthanatized. Outcome was available for 13 animals: 9 were used for breeding and
      4 as pets. Fewer major complications occurred with internal fixation than with
      external fixation with a transfixation pin cast (P<.005); however, there were no
      significant differences in minor complications between groups. CONCLUSIONS:
      Internal fixation with bone plates was associated with fewer major complications
      than external fixation with a transfixation pin cast.

PMID- 21175690
TI  - Effects of aerobic and anaerobic fluid collection on biochemical analysis of
      peritoneal fluid in healthy horses and horses with colic.
AB  - OBJECTIVE: To determine whether in healthy horses and those with colic, exposure
      of peritoneal fluid to room air affects values obtained on biochemical analysis.
      STUDY DESIGN: Prospective study. ANIMALS: Adult horses with a primary complaint
      of acute abdominal pain (n=29) and 12 healthy horses. METHODS: Peritoneal fluid
      was aseptically collected under aerobic and anaerobic conditions. After
      collection, pH, PCO(2) , PO(2) , HCO(3) (-) , Na(+) , ionized Ca(2+) , K(+) ,
      lactate, and glucose were immediately measured using a commercial blood gas
      analyzer. Biochemical variables were compared between aerobically and
      anaerobically obtained samples using a paired t-test. RESULTS: In healthy horses,
      peritoneal fluid samples collected under anaerobic conditions had higher PCO(2)
      and ionized Ca(2+) and lower PO(2) , HCO(3) (-) , and pH compared with samples
      exposed to air. No differences were observed for K(+) , Na(+) , glucose, and
      lactate. In horses with colic, samples collected anaerobically had higher PCO(2)
      , ionized Ca(2+) , Na(+) , and glucose and lower PO(2) , HCO(3) (-) , and pH
      value compared with samples exposed to air. No differences were observed for K(+)
      and lactate. CONCLUSION: Exposure of peritoneal fluid to room air had a
      significant effect on pH, PCO(2) , PO(2) , and variables associated or dependent
      on changes in pH such as HCO(3) (-) and ionized Ca(2+) . Interpretation of
      biochemical analysis of peritoneal fluid may be influenced by sample collection
      method.

PMID- 21175691
TI  - Racing and sales performance after unilateral or bilateral single transphyseal
      screw insertion for varus angular limb deformities of the carpus in 53
      thoroughbreds.
AB  - OBJECTIVE: To evaluate the racing and sales performance of Thoroughbred horses
      with varus angular limb deformities of the carpus treated by unilateral or
      bilateral single transphyseal screw (STS) placement. STUDY DESIGN: Case series.
      ANIMALS: Thoroughbred horses (n=53). METHODS: Medical records (January 1, 2005
      December 31, 2006) of yearling Thoroughbreds treated for carpal angular limb
      deformity by transphyseal screw insertion in the distal aspect of the radius were
      reviewed. Retrieved data were sex, surgery, and screw removal dates, surgical
      site, appearance, limb(s) affected, type of angular limb deformity, and degree of
      angular deviation measured by a goniometer. Racing and sales data were collected
      for analysis from an online racing site for all treated horses and their maternal
      siblings. RESULTS: No significant differences were identified between treated
      horses and their maternal siblings in yearling sale price, 2-year-olds in
      training sale price, percent starters, percent winners, and starts, earnings, and
      earnings/start made during the 2- and 3-year old years. CONCLUSIONS: No
      deleterious effects on sales or racing performance were identified after use of
      STS in the distal aspect of the radius of Thoroughbreds for the treatment of
      varus angular limb deformities of the carpus.

PMID- 21175692
TI  - Electrosurgical tenoscopic desmotomy of the accessory ligament of the superficial
      digital flexor muscle (proximal check ligament) in horses.
AB  - OBJECTIVE: To report a tenoscopic technique using monopolar electrosurgery to
      transect the accessory ligament of superficial digital flexor muscle (AL-SDFM)
      and outcome in 33 horses. STUDY DESIGN: Case series. ANIMALS: Horses (n=33).
      METHODS: Medical files and surgery video recordings of horses that had AL-SDFM
      desmotomy performed by tenoscopy with monopolar electrosurgical electrodes were
      reviewed. RESULTS: Of 33 horses, 24 were Standardbred racehorses with surgery
      performed bilaterally for superficial digital flexor tendonitis and 9 horses had
      flexural deformity. Severe (n=6) and mild (6) intrathecal hemorrhage was the most
      common intraoperative complication. Large intrathecal vessels including the
      nutrient artery were successfully electrocoagulated and AL-SDFM transection was
      completed. Clear/serosanguinous drainage from skin incisions was observed for
      4.3+/-3.3 days (mean, SD). Protracted wound drainage for >4 days occurred in 10
      horses, principally in the group treated for flexural deformities (P=.01).
      CONCLUSIONS: Sixty-four AL-SDFM were transected under tenoscopic observation
      using monopolar electrodes. Electrocoagulation of large intrathecal vessels,
      including the nutrient artery, was possible in all cases and allowed completion
      of desmotomy. Postoperative wound care was similar to routine tenoscopy in most
      (70%) horses. Aseptic protracted wound drainage was observed in 30% of horses
      (principally those with flexural deformity), and led to a prolonged
      hospitalization.

PMID- 21175693
TI  - Standing hand-assisted laparoscopic ovariectomy in 65 mares.
AB  - OBJECTIVE: To review the efficacy and safety of unilateral ovariectomy by use of
      a standing hand-assisted laparoscopic approach and evaluate the effect of ovary
      size on posttransection hemorrhage after application of a linear stapling device.
      STUDY DESIGN: Case series. ANIMALS: Horses (n=65) aged 2-20 years. METHODS:
      Medical records of mares that had ovariectomy performed by use of a standing hand
      assisted laparoscopic approach were reviewed. Data retrieved were signalment,
      ovary removed (left, right), ovarian size, ovarian pathology, intraoperative and
      postoperative complications, and length of hospitalization. RESULTS: Mean ovarian
      diameter was 17 cm. Histopathology (52 mares) confirmed 41 granulosa cell tumors
      (79%), 8 ovarian cysts (15%), 1 teratoma (2%), and 2 ovaries (4%) without
      abnormalities. Hemorrhage was observed laparoscopically in 16 mares after
      transection of the mesovarium. Complications encountered during surgery included
      1 mare collapsing in the stocks and 1 mare that hemorrhaged excessively from the
      incision. Postoperative complications included 2 cases of mild colic. Overall
      complication rate was 6%. CONCLUSIONS: All attempts to remove the target ovary
      were successful. The approach is safe for the mare, as complications encountered
      were similar to those recently reported for other approaches.

PMID- 21175694
TI  - Comparison of healing of the osteotomy gap after tibial tuberosity advancement
      with and without use of an autogenous cancellous bone graft.
AB  - OBJECTIVE: To evaluate and compare healing, with and without the use of bone
      graft, of the gap created during tibial tuberosity advancement (TTA). STUDY
      DESIGN: Prospective study and case series. ANIMALS: Dogs treated with TTA (n=67).
      METHODS: Prospective study: Mediolateral radiographic projections (6 weeks and 4
      months) after TTA without use of bone graft (group I, n=14) were compared with
      radiographs of consecutive TTA in which the gap was filled with autologous
      cancellous bone graft (group II, n=14). Two scoring techniques (A, B) were used.
      Score A was used to grade the overall osteotomy healing (0=no healing, 4=healed
      osteotomy). Score B evaluated, independently of each other, healing in 3 sites:
      proximal to the cage (B1), between cage and plate (B2), and distal to the plate
      (B3). CASE SERIES: nongrafted TTA (4-25 weeks, n=39) were evaluated for healing
      (Score A). Data was analyzed using t-tests and ANOVA. Significance was set at
      P<=.05. RESULTS: Prospective study: Score A, B2, and B3 showed no difference in
      healing between groups at 6.8 weeks and 4.2 months. Score B1 revealed, in both
      rechecks, a significantly higher density in group II. case series: Radiographs at
      11.59+/-5.99 weeks scored 3.3 (2-4). No healing related complications were
      observed. CONCLUSION: The osteotomy gap created during TTA healed within expected
      time regardless of bone graft use.

PMID- 21175695
TI  - Microfenestration using the CUSA Excel ultrasonic aspiration system in
      chondrodystrophic dogs with thoracolumbar disk extrusion: a descriptive cadaveric
      and clinical study.
AB  - OBJECTIVE: To describe an ultrasonic surgical aspirator assisted disk
      fenestration technique in dogs. STUDY DESIGN: Descriptive cadaveric and
      prospective clinical study. ANIMALS: Fresh Beagle cadavers (n=5) and 10
      chondrodystrophic dogs with thoracolumbar disk extrusion. METHODS: Cadaveric
      study: Intervertebral disks T12-L2 were fenestrated with the CUSA Excel in 5
      Beagle cadavers, and fenestration efficacy assessed by morphologic examination of
      the completeness of fenestration and size of annulotomy. Clinical study: the
      affected intervertebral disk was fenestrated in 10 chondrodystrophic dogs treated
      by hemilaminectomy for thoracolumbar disk disease. Efficacy of fenestration was
      evaluated. RESULTS: Mean time necessary to perform CUSA assisted fenestration was
      8 minutes (range, 5-10 minutes) for each disk in cadavers and patients. In
      cadaver spines, removal of the nucleus pulposus was complete in 11/15 disks. In 4
      disks, remnants of nucleus pulposus material were observed on the contralateral
      side. Nuclear material was normal in 9/15 disks and showed evidence of chondroid
      degeneration on histopathologic examination in the 6 disks. Median annulotomy
      size was 3 mm. Clinically, no signs of early recurrence were observed and all
      dogs recovered uneventfully. CONCLUSIONS: CUSA assisted fenestration is a safe
      and efficient method of fenestration for removal of most of the nucleus pulposus
      through a limited annulotomy.

PMID- 21175696
TI  - Bacterial diversity of field-caught mosquitoes, Aedes albopictus and Aedes
      aegypti, from different geographic regions of Madagascar.
AB  - Symbiotic bacteria are known to play important roles in the biology of insects,
      but the current knowledge of bacterial communities associated with mosquitoes is
      very limited and consequently their contribution to host behaviors is mostly
      unknown. In this study, we explored the composition and diversity of mosquito
      associated bacteria in relation with mosquitoes' habitats. Wild Aedes albopictus
      and Aedes aegypti were collected in three different geographic regions of
      Madagascar. Culturing methods and denaturing gradient gel electrophoresis (DGGE)
      and sequencing of the rrs amplicons revealed that Proteobacteria and Firmicutes
      were the major phyla. Isolated bacterial genera were dominated by Bacillus,
      followed by Acinetobacter, Agrobacterium and Enterobacter. Common DGGE bands
      belonged to Acinetobacter, Asaia, Delftia, Pseudomonas, Enterobacteriaceae and an
      uncultured Gammaproteobacterium. Double infection by maternally inherited
      Wolbachia pipientis prevailed in 98% of males (n=272) and 99% of females (n=413);
      few individuals were found to be monoinfected with Wolbachia wAlbB strain.
      Bacterial diversity (Shannon-Weaver and Simpson indices) differed significantly
      per habitat whereas evenness (Pielou index) was similar. Overall, the bacterial
      composition and diversity were influenced both by the sex of individuals and by
      the environment inhabited by the mosquitoes; the latter might be related to both
      the vegetation and the animal host populations that Aedes used as food sources.

PMID- 21175697
TI  - Hydrology is reflected in the functioning and community composition of
      methanotrophs in the littoral wetland of a boreal lake.
AB  - In lake ecosystems a major proportion of methane (CH(4) ) emissions originate
      from the littoral zone, which can have a great spatial variability in hydrology,
      soil quality and vegetation. Hitherto, spatial heterogeneity and the effects it
      has on functioning and diversity of methanotrophs in littoral wetlands have been
      poorly understood. A diagnostic microarray based on the particulate methane
      monooxygenase gene coupled with geostatistics was used to analyse spatial
      patterns of methanotrophs in the littoral wetland of a eutrophic boreal lake
      (Lake Kevaton, Eastern Finland). The wetland had a hydrology gradient with a mean
      water table varying from -8 to -25 cm. The wettest area, comprising the highest
      CH(4) oxidation, had the highest abundance and species richness of methanotrophs.
      A high water table favoured the occurrence of type Ib methanotrophs, whereas
      types Ia and II were found under all moisture conditions. Thus the spatial
      heterogeneity in functioning and diversity of methanotrophs in littoral wetlands
      is highly dependent on the water table, which in turn varies spatially in
      relation to the geomorphology of the wetland. We suggest that changes in water
      levels resulting from regulation of lakes and/or global change will affect the
      abundance, activity and diversity of methanotrophs, and consequently CH(4)
      emissions from such systems.

PMID- 21175698
TI  - Modelling Biolog profiles' evolution for yeast growth monitoring in alcoholic
      fermentation.
AB  - AIMS: A research was undertaken to explore the possibility to express with
      suitable mathematical models Biolog metabolic curves obtained for oenological
      yeasts and to use such models for monitoring yeast growth in alcoholic
      fermentation. METHODS AND RESULTS: Experimental curves of metabolic activity in
      Biolog YT microplates, obtained in a previous work for various oenological yeast
      strains in pure cultures and mixed populations, at various cell concentrations,
      have been modelled with Gompertz's, Gompertz's modified and Lindstrom's
      mathematical equations. Lindstrom's model proved to be the most suitable to fit
      the curves of the oenological yeasts under study, providing the highest
      correlation coefficients between experimental and calculated data. The model made
      it possible to recognize, in mixed yeast populations, the presence of active dry
      yeasts used for guided fermentations. Model's constant parameters were used for a
      numerical characterization of yeast curves. CONCLUSIONS:   The application of the
      model to the experimental data resulted to be suitable for an early prediction of
      the successive evolution of yeast growth. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The results obtained indicate the possibility to develop protocols for monitoring
      yeast presence during alcoholic fermentation, with an early assessment of the
      correct evolution of their growth, especially when active dry yeasts are
      employed.

PMID- 21175699
TI  - Knocking out of tailoring genes eryK and eryG in an industrial erythromycin
      producing strain of Saccharopolyspora erythraea leading to overproduction of
      erythromycin B, C and D at different conversion ratios.
AB  - AIMS:  To overproduce erythromycin C, B or D and evaluate the effect of
      disruption of tailoring genes eryK and eryG in an industrial erythromycin
      producer. METHODS AND RESULTS:   The tailoring genes eryG and eryK were
      inactivated individually or simultaneously by targeted gene disruption in an
      industrial strain Saccharopolyspora erythraea HL3168 E3, resulting in the
      overproduction of erythromycin C (2.48 g l(-1) ), B (1.70 g l(-1) ) or D (2.15 g
      l(-1) ) in the mutant strain QL-G, QL-K or QL-KG, respectively. Analysis of the
      erythromycin congeners throughout the fermentation indicated that, at the end of
      fermentation, comparatively large amount of erythromycin D (0.67 g l(-1) ) was
      accumulated in QL-G, whereas only small amount of erythromycin D (0.10 g l(-1) )
      was produced in QL-K. CONCLUSIONS: Inactivation of tailoring genes eryG and eryK
      in the high producer did not affect the biosynthesis of erythromycin. However,
      erythromycin D could be more efficiently methylated by EryG than be hydroxylated
      by EryK. SIGNIFICANCE AND IMPACT OF THE STUDY: Development of the mutant strains
      provides a method for the economical large-scale production of potent lead
      compounds. The information about the accumulation and conversion of erythromycins
      in the industrial strains may contribute to further improving erythromycin
      production.

PMID- 21175700
TI  - Quantification of the influence of trimethylamine-N-oxide (TMAO) on the heat
      resistance of Escherichia coli K12 at lethal temperatures.
AB  - AIM: To quantify the influence of trimethylamine-N-oxide (TMAO) on the heat
      resistance of Escherichia coli K12 MG1655 cells at static temperatures. METHODS
      AND RESULTS: Stationary-phase E. coli cells were inactivated at 52, 54 and 58
      degrees C. The heat resistance is described as reduction in the inactivation
      rate, k(max) , and/or an increase in the time for one decimal reduction, D,
      and/or an increase in the time for the fourth decimal reduction, t(4D) .
      CONCLUSIONS: Resistance of E. coli changed - increased - at all temperatures
      under study. Generally, the addition of TMAO to the growth medium protected E.
      coli cells, leading to an increase in their heat resistance, i.e. reduced k(max)
      and increased D and t(4D) values are obtained. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Additional knowledge on the reaction of E. coli to heat in the presence of
      the organic osmolyte TMAO at lethal temperatures is provided. This work
      contributes to an improved understanding of the level of the resistance of
      bacteria to heat in the presence of osmolytes.

PMID- 21175701
TI  - Cloning and sequencing of biofilm-associated protein (bapA) gene and its
      occurrence in different serotypes of Salmonella.
AB  - AIMS: Salmonella spp. has the capability to form biofilm on various surfaces.
      Biofilm-associated protein (bapA), a large surface protein has been shown to play
      a leading role in the development of biofilm in Salmonella. Objective of this
      study was to investigate the presence of bapA gene in different serotypes of
      Salmonella spp. and to characterize DNA fragment encoding bapA protein of
      Salmonella Enteritidis. METHODS AND RESULTS: Sixty-seven Salmonella strains
      belonging to 34 serovars isolated from diverse sources in India were screened for
      the presence of bapA gene employing a primer designed for the purpose. All the
      strains yielded a positive amplification indicating that the bapA gene is well
      conserved in Salmonella spp. The amplified gene fragment of bapA was cloned in
      Escherichia coli (DH5 alpha) cells by using pGEM-T easy cloning vector. On
      partial sequence analysis, the product exhibited 667 base pairs, corresponding to
      218 amino acids. CONCLUSIONS:   BapA gene was found to be highly conserved in
      Salmonella. Partial sequence analysis of this gene from a strain of Salm.
      Enteritidis revealed close association with serotypes of poultry origin and also
      with some other animal/zoonotic serotypes. SIGNIFICANCE AND IMPACT OF THE STUDY:
      BapA gene can be targeted for the genus-specific detection of this organism from
      different sources. Antigenic index of bapA protein indicates its protective and
      diagnostic potentials.

PMID- 21175702
TI  - Mutations in the myostatin gene leading to hypermuscularity in mammals:
      indications for a similar mechanism in fish?
AB  - The transforming growth factor beta (TGF-beta) superfamily encodes secreted
      factors that are important in regulating embryonic development and tissue
      homeostatis in adults. Myostatin (MSTN, encoded by MSTN) or 'growth and
      differentiation factor 8', a member of this superfamily, is a negative regulator
      of skeletal muscle growth and is highly conserved among animal species. In 1997,
      a mutation associated with the so-called double-muscling phenotype in cattle was
      found in the MSTN gene. During the years following the discovery of the first
      MSTN mutation, other mutations were found in cattle and other mammalian species,
      and MSTN became one of the most thoroughly studied genes in animals. The aim of
      this review is mainly to describe the functional mutations located in the MSTN
      genes of several mammalian species, leading to double muscling in these animals.
      Furthermore, in light of the increasing importance of fish genetics, the
      possibility of functional mutations in piscine MSTN with a similar effect as in
      mammals, and a genetic model for MSTN research in fish, will also be discussed.

PMID- 21175703
TI  - Development of genetic markers in abalone through construction of a SNP database.
AB  - In the absence of a reference genome, single-nucleotide polymorphisms (SNP)
      discovery in a group of abalone species was undertaken by random sequence
      assembly. A web-based interface was constructed, and 11 932 DNA sequences from
      the genus Haliotis were assembled, with 1321 contigs built. Of these, 118 contigs
      that consisted of at least ten annotation groups were selected. The 1577 putative
      SNPs were identified from the 118 contigs, with SNPs in several HSP70 gene
      contigs confirmed by PCR amplification of an 809-bp DNA fragment. SNPs in the
      HSP70 gene were compared across eight abalone species. A total of 129 polymorphic
      sites, including heterozygote sites within and among species, were observed.
      Phylogenetic analysis of the partial HSP70 gene region showed separation of the
      tested abalone into two groups, one reflecting the southern hemisphere species
      and the other the northern hemisphere species. Interestingly, Haliotis iris from
      New Zealand showed a closer relationship to species distributed in the northern
      Pacific region. Although HSP genes are known to be highly conserved among taxa,
      the validation of polymorphic SNPs from HSP70 in this mollusc demonstrates the
      applicability of cross-species SNP markers in abalone and the first step towards
      universal nuclear markers in Haliotis.

PMID- 21175704
TI  - Intragastric acidity during administration of generic omeprazole or esomeprazole 
      a randomised, two-way crossover study including CYP2C19 genotyping.
AB  - BACKGROUND: Generic omeprazole has been approved in many countries for the
      treatment of acid-related gastrointestinal disorders. However, clinical studies
      comparing generic to original proton pump inhibitors are limited. AIMS: To
      compare the effect of generic omeprazole 20 mg/day with esomeprazole 20 mg/day on
      intragastric acidity and to investigate the influence of the CYP2C19 metabolizer
      status. METHODS: In this randomised, single-blinded, two-way crossover study, 24
      healthy Helicobacter pylori-negative subjects, received generic omeprazole (Omep;
      Hexal AG, Holzkirchen, Germany) 20 mg once daily or esomeprazole 20 mg once daily
      for five consecutive days. Twenty-four-hour intragastric pH was recorded on day 5
      of each treatment. CYP2C19 status was determined by polymerase chain reaction
      restriction fragment length polymorphism. RESULTS: Over all, there were no
      statistically significant differences between generic omeprazole and esomeprazole
      with respect to median intragastric pH (3.5 and 3.9, P = 0.07), the total hours
      with intragastric pH >4 (10.4 and 11.3, P = 0.29), and during upright (9.6 and
      9.1, P = 0.77) or supine (2.2 and 2.2, P = 0.94) position. However, in CYP2C19
      rapid metabolizers, esomeprazole was superior to omeprazole, with the percentage
      of time with intragastric pH >3.0 and pH >3.5 being higher with esomeprazole than
      with generic omeprazole [Delta = 9% (P = 0.026) and Delta = 8% (P = 0.046),
      respectively]. CONCLUSIONS: Overall, generic omeprazole 20 mg appears to provide
      a similar intragastric acid control when compared with esomeprazole 20 mg.
      However, esomeprazole might be advantageous in subjects with a rapid CYP2C19
      metabolizer status.

PMID- 21175705
TI  - Current antiviral combination therapy for chronic hepatitis C patients who failed
      to interferon alfa-based treatment.
AB  - WHAT IS KNOWN AND OBJECTIVE: Interferon-alfa-based therapy is effective in the
      treatment of Hepatitis C. However, some patients fail to respond and others
      relapse, after initially responding. Our objective was to assess the efficacy,
      safety and predictive factors for sustained virological response (SVR) to
      peginterferon plus ribavirin in chronic hepatitis C patients who failed to
      interferon-alfa (IFNalpha)-based therapy. METHODS: Seventy-five consecutive
      patients who failed to IFNalpha-based therapy were retreated with peginterferon
      plus ribavirin. Of these patients, 85% were infected by genotype 1. The primary
      endpoint was SVR. RESULTS AND DISCUSSION: Of 75 non-responder (n = 54) or
      relapser patients (n = 21), 50 were previously treated with IFNalpha-monotherapy
      and 25 with IFNalpha plus ribavirin. Global SVR rate was 41.3%: for patients re
      treated with IFNalpha the response was 48% whilst for those retreated with
      IFNalpha plus ribavirin, it was 28%. For previous non-responders the SVR rate was
      37% and for relapsers it was 52.4%. WHAT IS NEW AND CONCLUSION: Retreatment with
      peginterferon plus ribavirin is an effective option for some chronic hepatitis C
      non-responder or relapser patients. Higher SVR rate was achieved in relapsers and
      in those patients who received IFNalpha monotherapy previously.

PMID- 21175707
TI  - Publishing bioethics and bioethics--reflections on academic publishing by a
      journal editor.
AB  - This article by one of the Editors of Bioethics, published in the 25th
      anniversary issue of the journal, describes some of the revolutionary changes
      academic publishing has undergone during the last decades. Many humanities
      journals went from typically small print-runs, counting by the hundreds, to on
      line availability in thousands of university libraries worldwide. Article up-take
      by our subscribers can be measured efficiently. The implications of this and
      other changes to academic publishing are discussed. Important ethical challenges
      need to be addressed in areas such as the enforcement of plagiarism-related
      policies, the so-called 'impact factor' and its impact on academic integrity, and
      the question of whether on-line only publishing can currently guarantee the
      integrity of academic publishing histories.

PMID- 21175708
TI  - Personal genomes: no bad news?
AB  - Issues in genetics and genomics have been centre stage in Bioethics for much of
      its history, and have given rise to both negative and positive imagined futures.
      Ten years after the completion of the Human Genome Project, it is a good time to
      assess developments. The promise of whole genome sequencing of individuals
      requires reflection on personalization, genetic determinism, and privacy.

PMID- 21175709
TI  - Was bioethics founded on historical and conceptual mistakes about medical
      paternalism?
AB  - Bioethics has a founding story in which medical paternalism, the interference
      with the autonomy of patients for their own clinical benefit, was an accepted
      ethical norm in the history of Western medical ethics and was widespread in
      clinical practice until bioethics changed the ethical norms and practice of
      medicine. In this paper I show that the founding story of bioethics misreads
      major texts in the history of Western medical ethics. I also show that a major
      source for empirical claims about the widespread practice of medical paternalism
      has been misread. I then show that that bioethics based on its founding story
      deprofessionalizes medical ethics. The result leaves the sick exposed to the
      predatory power of medical practitioners and healthcare organizations with only
      their autonomy-based rights to non-interference, expressed in contracts, to
      protect them. The sick are stripped of the protection afforded by a professional,
      fiduciary relationship of physicians to their patients. Bioethics based on its
      founding story reverts to the older model of a contractual relationship between
      the sick and medical practitioners not worthy of intellectual or moral trust
      (because such trust cannot be generated by what I call 'deprofessionalizing
      bioethics'). On closer examination, bioethics based on its founding story,
      ironically, eliminates paternalism as a moral category in bioethics, thus causing
      bioethics to collapse on itself because it denies one of the necessary conditions
      for medical paternalism. Bioethics based on its founding story should be
      abandoned.

PMID- 21175710
TI  - Looking backwards, looking forward: hopes for bioethics' next twenty-five years.
AB  - I reflect on the past, present, and future of the field of bioethics. In so
      doing, I offer a very situated overview of where bioethics has been, where it now
      is, where it seems to be going, where I think we could do better, and where I
      dearly hope the field will be heading. I also propose three ways of re-orienting
      our theoretic tools to guide us in a new direction: (1) adopt an ethics of
      responsibility; (2) explore the responsibilities of various kinds of actors and
      relationships among them; (3) expand the types of participants engaged in
      bioethics.

PMID- 21175711
TI  - Localized past, globalized future: towards an effective bioethical framework
      using examples from population genetics and medical tourism.
AB  - This paper suggests that many of the pressing dilemmas of bioethics are global
      and structural in nature. Accordingly, global ethical frameworks are required
      which recognize the ethically significant factors of all global actors. To this
      end, ethical frameworks must recognize the rights and interests of both
      individuals and groups (and the interrelation of these). The paper suggests that
      the current dominant bioethical framework is inadequate to this task as it is
      over-individualist and therefore unable to give significant weight to the ethical
      demands of groups (and by extension communal and public goods). It will explore
      this theme by considering the inadequacy of informed consent (the 'global
      standard' of bioethics) to address two pressing global bioethical issues: medical
      tourism and population genetics. Using these examples it will show why consent is
      inadequate to address all the significant features of these ethical dilemmas.
      Four key failures will be explored, namely, * That the rights and interests of
      those related (and therefore affected) are neglected; * That consent fails to
      take account of the context and commitments of individuals which may constitute
      inducement and coercion; * That consent alone does not have the ethical weight to
      negate exploitation or make an unjust action just ('the fallacy of sufficiency');
      * That consent is a single one-off act which is inappropriate for the types of
      decision being made. It will conclude by suggesting that more appropriate models
      are emerging, particularly in population genetics, which can supplement consent.

PMID- 21175712
TI  - In whose interest? Policy and politics in assisted reproduction.
AB  - This paper interprets the British legislative process that initiated the first
      comprehensive national regulation of embryo research and fertility services and
      examines subsequent efforts to restrain the assisted reproduction industry. After
      describing and evaluating British regulatory measures, I consider successive
      failures to control the assisted reproduction industry in the US. I discuss
      disparities between UK and US regulatory initiatives and their bearing on
      regulation in other countries. Then I turn to the political and social structures
      in which the assisted reproduction industry is embedded. I argue that regulatory
      bodies are seldom neutral arbiters. They tend to respond most readily to special
      interests and neglect strategies that could more effectively meet the health
      needs of the people they represent. Neither national nor international bodies
      have aggressively pursued policies to harness the industry, reduce infertility
      rates, or meet the needs of people whose fertility is threatened by substandard
      healthcare and environmental neglect. In conclusion, I consider recent
      initiatives by activist groups to mount an alternative response to the industry's
      current practices and build a transnational reproductive justice movement.

PMID- 21175713
TI  - Allometric scaling: analysis of LD50 data.
AB  - The need to identify toxicologically equivalent doses across different species is
      a major issue in toxicology and risk assessment. In this article, we investigate
      interspecies scaling based on the allometric equation applied to the single, oral
      LD (50) data previously analyzed by Rhomberg and Wolff. We focus on the
      statistical approach, namely, regression analysis of the mentioned data. In
      contrast to Rhomberg and Wolff's analysis of species pairs, we perform an overall
      analysis based on the whole data set. From our study it follows that if one
      assumes one single scaling rule for all species and substances in the data set,
      then beta = 1 is the most natural choice among a set of candidates known in the
      literature. In fact, we obtain quite narrow confidence intervals for this
      parameter. However, the estimate of the variance in the model is relatively high,
      resulting in rather wide prediction intervals.

PMID- 21175714
TI  - Reversing nuclear opposition: evolving public acceptance of a permanent nuclear
      waste disposal facility.
AB  - Nuclear facilities have long been seen as the top of the list of locally unwanted
      land uses (LULUs), with nuclear waste repositories generating the greatest
      opposition. Focusing on the case of the Waste Isolation Pilot Plant (WIPP) in
      southern New Mexico, we test competing hypotheses concerning the sources of
      opposition and support for siting the facility, including demographics,
      proximity, political ideology, and partisanship, and the unfolding policy process
      over time. This study tracks the changes of risk perception and acceptance of
      WIPP over a decade, using measures taken from 35 statewide surveys of New Mexico
      citizens spanning an 11-year period from fall 1990 to summer 2001. This time span
      includes periods before and after WIPP became operational. We find that
      acceptance of WIPP is greater among those whose residences are closest to the
      WIPP facility. Surprisingly, and contrary to expectations drawn from the broader
      literature, acceptance is also greater among those who live closest to the
      nuclear waste transportation route. We also find that ideology, partisanship,
      government approval, and broader environmental concerns influence support for
      WIPP acceptance. Finally, the sequence of procedural steps taken toward formal
      approval of WIPP by government agencies proved to be important to gaining public
      acceptance, the most significant being the opening of the WIPP facility itself.

PMID- 21175715
TI  - How people perceive and will cope with risks from the diffusion of ubiquitous
      information and communication technologies.
AB  - Information and communication technologies (ICTs) are increasingly pervasive and
      continue to reshape our environment. This trend carries different risks.
      Therefore, the early sensitization of people to these risks, as well as improving
      their capacity for protective coping behavior, is essential. Based on the
      protection motivation theory (PMT), we examined with structural equation modeling
      the relationships between different components of threat and coping appraisal to
      explain protective and nonprotective responses. Calculations were performed with
      data from a representative survey on perception and use of ICT among German
      residents (N= 5,030). Our findings largely supported the proposed model: an
      increased perceived threat was positively related to the intentions to react
      protectively and nonprotectively. Perceived coping efficacy increased the
      protective and decreased the nonprotective responses. Negative affect enhanced
      the perceived threat and the nonprotective response, but inhibited protective
      intentions. The implications of these findings on how to sensitize people to the
      risks of these new technologies are outlined.

PMID- 21175716
TI  - Evaluation of legal liability for technological risks in view of requirements for
      peaceful coexistence and progress.
AB  - Legal liability for risk-generating technological activities is evaluated in view
      of requirements that are necessary for peaceful human coexistence and progress in
      order to show possibilities for improvement. The requirements imply, given that
      political decision making about the activities proceeds on the basis of majority
      rule, that legal liability should be unconditional (absolute, strict) and
      unlimited (full). We analyze actual liability in international law for various
      risk-generating technological activities, to conclude that nowhere is the
      standard of unconditional and unlimited liability fully met. Apart from that
      there are enormous differences. Although significant international liability
      legislation is in place for some risk-generating technological activities,
      legislation is virtually absent for others. We discuss fundamental possibilities
      and limitations of liability and private insurance to secure credible and
      ethically sound risk assessment and risk management practices. The limitations
      stem from problems of establishing a causal link between an activity and a harm;
      compensating irreparable harm; financial warranty; moral hazard in insurance and
      in organizations; and discounting future damage to present value. As our
      requirements call for prior agreement among all who are subjected to the risks of
      an activity about the settlement of these difficult problems, precautionary ex
      ante regulation of risk-generating activities may be a more attractive option,
      either combined with liability stipulations or not. However, if ex ante
      regulation is not based on the consent of all subjected to the risks, it remains
      that the basis of liability in the law should be unconditional and unlimited
      liability.

PMID- 21175717
TI  - Estimation of the likelihood of fecal-oral HEV transmission among pigs.
AB  - Sources for human hepatitis E virus (HEV) infections of genotype 3 are largely
      unknown. Pigs are potential animal reservoirs for HEV. Intervention at pig farms
      may be desired when pigs are confirmed as a source for human infections,
      requiring knowledge about transmission routes. These routes are currently
      understudied. The current study aims to quantify the likelihood of pig feces in
      causing new HEV infections in pigs due to oral ingestion. We estimated the daily
      infection risk for pigs by modeling the fate of HEV in the fecal-oral (F-O)
      pathway. Using parameter values deemed most plausible by the authors based on
      current knowledge the daily risk of infection was 0.85 (95% interval: 0.03-1).
      The associated expected number of new infections per day was ~4 (2.5% limit 0.1,
      the 97% limit tending to infinity) compared to 0.7 observed in a transmission
      experiment with pigs, and the likelihood of feces causing the transmission
      approached 1. In alternative scenarios, F-O transmission of HEV was also very
      likely to cause new infections. By reducing the total value of all explanatory
      variables by 2 orders of magnitude, the expected numbers of newly infected pigs
      approached the observed number. The likelihood of F-O transmission decreased by
      decreasing parameter values, allowing for at most 94% of infections being caused
      by additional transmission routes. Nevertheless, in all scenarios F-O
      transmission was estimated to contribute to HEV transmission. Thus, despite the
      difficulty in infecting pigs with HEV via oral inoculation, the F-O route is
      likely to cause HEV transmission among pigs.

PMID- 21175718
TI  - Methodology for the calculation of annualized incremental risks in systems of
      dams.
AB  - In the past few years, the field of dam safety has approached risk informed
      methodologies throughout the world and several methodologies and programs are
      appearing to aid in the systematization of the calculations. The most common way
      of implementing these calculations is through the use of event trees, computing
      event probabilities, and incremental consequences. This methodology is flexible
      enough for several situations, but its generalization to the case of systems of
      several dams is complex and its implementation in a completely general
      calculation methodology presents some problems. Retaining the event tree
      framework, a new methodology is proposed to calculate incremental risks. The main
      advantage of this proposed methodology is the ease with which it can be applied
      to systems of several dams: with a single risk model that describes the complete
      system and with a single calculation the incremental risks of the system can be
      obtained, being able to allocate the risk of each dam and of each failure mode.
      The article shows how both methodologies are equivalent and also applies them to
      a case study.

PMID- 21175719
TI  - Vulnerability, risk perception, and health profile of marginalized people exposed
      to multiple built-environment stressors in Worcester, Massachusetts: a pilot
      project.
AB  - Millions of low-income people of diverse ethnicities inhabit stressful old urban
      industrial neighborhoods. Yet we know little about the health impacts of built
      environment stressors and risk perceptions in such settings; we lack even basic
      health profiles. Difficult access is one reason (it took us 30 months to survey
      80 households); the lack of multifaceted survey tools is another. We designed and
      implemented a pilot vulnerability assessment tool in Worcester, Massachusetts. We
      answer: (1) How can we assess vulnerability to multiple stressors? (2) What is
      the nature of complex vulnerability-including risk perceptions and health
      profiles? (3) How can findings be used by our wider community, and what lessons
      did we learn? (4) What implications arise for science and policy? We sought a
      holistic picture of neighborhood life. A reasonably representative sample of 80
      respondents captured data for 254 people about: demographics, community concerns
      and resources, time-activity patterns, health information, risk/stress
      perceptions, and resources/capacities for coping. Our key findings derive partly
      from the survey data and partly from our experience in obtaining those data. Data
      strongly suggest complex vulnerability dominated by psychosocial stress.
      Unexpected significant gender and ethnic disease disparities emerged: notably,
      females have twice the disease burden of males, and white females twice the
      burden of females of color (p < 0.01). Self-reported depression differentiated by
      gender and age is illustrative. Community based participatory research (CBPR)
      approaches require active engagement with marginalized populations, including
      representatives as funded partners. Complex vulnerability necessitates holistic,
      participatory approaches to improve scientific understanding and societal
      responses.

PMID- 21175720
TI  - Failure probability under parameter uncertainty.
AB  - In many problems of risk analysis, failure is equivalent to the event of a random
      risk factor exceeding a given threshold. Failure probabilities can be controlled
      if a decisionmaker is able to set the threshold at an appropriate level. This
      abstract situation applies, for example, to environmental risks with
      infrastructure controls; to supply chain risks with inventory controls; and to
      insurance solvency risks with capital controls. However, uncertainty around the
      distribution of the risk factor implies that parameter error will be present and
      the measures taken to control failure probabilities may not be effective. We show
      that parameter uncertainty increases the probability (understood as expected
      frequency) of failures. For a large class of loss distributions, arising from
      increasing transformations of location-scale families (including the log-normal,
      Weibull, and Pareto distributions), the article shows that failure probabilities
      can be exactly calculated, as they are independent of the true (but unknown)
      parameters. Hence it is possible to obtain an explicit measure of the effect of
      parameter uncertainty on failure probability. Failure probability can be
      controlled in two different ways: (1) by reducing the nominal required failure
      probability, depending on the size of the available data set, and (2) by
      modifying of the distribution itself that is used to calculate the risk control.
      Approach (1) corresponds to a frequentist/regulatory view of probability, while
      approach (2) is consistent with a Bayesian/personalistic view. We furthermore
      show that the two approaches are consistent in achieving the required failure
      probability. Finally, we briefly discuss the effects of data pooling and its
      systemic risk implications.

PMID- 21175722
TI  - Atypical fibrous histiocytoma with aberrant cytokeratin-5/6 expression.

PMID- 21175723
TI  - Review revue.

PMID- 21175727
TI  - A probabilistic transmission model to assess infection risk from Mycobacterium
      tuberculosis in commercial passenger trains.
AB  - The objective of this article is to characterize the risk of infection from
      airborne Mycobacterium tuberculosis bacilli exposure in commercial passenger
      trains based on a risk-based probabilistic transmission modeling. We investigated
      the tuberculosis (TB) infection risks among commercial passengers by inhaled
      aerosol M. tuberculosis bacilli and quantify the patterns of TB transmission in
      Taiwan High Speed Rail (THSR). A deterministic Wells-Riley mathematical model was
      used to account for the probability of infection risk from M. tuberculosis
      bacilli by linking the cough-generated aerosol M. tuberculosis bacilli
      concentration and particle size distribution. We found that (i) the quantum
      generation rate of TB was estimated with a lognormal distribution of geometric
      mean (GM) of 54.29 and geometric standard deviation (GSD) of 3.05 quantum/h at
      particle size <= 5 MUm and (ii) the basic reproduction numbers (R(0) ) were
      estimated to be 0.69 (0.06-6.79), 2.82 (0.32-20.97), and 2.31 (0.25-17.69) for
      business, standard, and nonreserved cabins, respectively. The results indicate
      that commercial passengers taking standard and nonreserved cabins had higher
      transmission risk than those in business cabins based on conservatism. Our
      results also reveal that even a brief exposure, as in the bronchoscopy cases, can
      also result in a transmission when the quantum generation rate is high. This
      study could contribute to a better understanding of the dynamics of TB
      transmission in commercial passenger trains by assessing the relationship between
      TB infectiousness, passenger mobility, and key model parameters such as seat
      occupancy, ventilation rate, and exposure duration.

PMID- 21175728
TI  - "Conundrums?".

PMID- 21175729
TI  - Hip fracture patients' cognitive state affects family members' experiences - a
      diary study of the hip fracture recovery.
AB  - BACKGROUND: Many patients with hip fractures suffer from dementia disease, which
      has shown to affect the outcome of recovery strongly, as well as care and
      treatment. As most hip fracture patients are discharged home early after surgery,
      caregiving often falls on family members - spouses, daughters, sons, or even
      neighbours become informal carers. AIM: To explore how hip fracture patients'
      cognitive state affect family members' experiences during the recovery period.
      METHODS: Eleven diaries written by family members' of hip fracture patients were
      analysed by means of qualitative content analysis. FINDINGS: The analysis
      generated two main categories with four categories. The first main category was;
      'Being a family member of a cognitively impaired patient' with the categories
      'Dissatisfaction with lack of support' and 'Emotional distress due to the
      patient's suffering'. The second main category was 'Being a family member of a
      cognitively intact patient' with the categories 'Satisfaction with a relative's
      successful recovery' and 'Strain due to their caring responsibilities'. Being a
      family member of a patient with cognitive impairment and a hip fracture meant
      being solely responsible for protecting the interests of the patient; in regard
      to care, rehabilitation and resources. The family members were also burdened with
      feelings of powerlessness and sadness due to the patients' suffering. On the
      contrary, family members of cognitively intact hip fracture patients had positive
      experiences. The family members expressed pleasure from seeing their close ones
      make progress. However, when the healing process was delayed this led to strain
      on the family members. CONCLUSIONS: The findings suggest the hip fracture
      patient's cognitive state is more decisive than the hip fracture itself for the
      family members' experiences.

PMID- 21175730
TI  - Women's experience of a myocardial infarction: 5 years later.
AB  - BACKGROUND: Myocardial infarction (MI) has long been seen as a male disease
      despite the fact that it is also a health problem for women. Factors that may
      influence their recovery, such as co-morbidity and requirements for support, have
      received less scientific attention. AIM: To explore and describe how women
      conceived their health and daily life 5 years after an MI. METHOD: An explorative
      and descriptive approach inspired by phenomenography was chosen as the design.
      The present study includes 12 women who have been described in earlier short-term
      studies. FINDINGS: The women described how the MI caused limitations in their
      lives even 5 years after the MI. They experienced physical restrictions, fatigue
      and also other health complaints. Furthermore, the older women suffered from
      various co-morbidities such as diabetes, kidney disease, high blood pressure, and
      stroke. Some women did not perceive their heart disease to interfere in daily
      life. Many of the women had thoughts about having a new MI. Furthermore, some
      women were grateful and described it as having a second opportunity. CONCLUSION: 
      The present study indicates how women in the recovery process 5 years after an
      MI still need support to continue with lifestyle changes. The women continue to
      struggle with different kinds of issues, such as financial stress, co-morbidity
      and side effects of medication. Support from the health care only in the first
      year after the MI is not enough. The women should benefit from the possibility to
      visit or consult professionals in primary care with knowledge of CHD.

PMID- 21175731
TI  - Motivation for lifestyle changes to improve health in people with impaired
      glucose tolerance.
AB  - AIM: To identify factors that could have motivational significance for lifestyle
      change to facilitate the reduction of Impaired Glucose Tolerance (IGT) and,
      consequently, the risk of having type 2 diabetes. METHODS: Eighteen people living
      in a municipality in central Norway participated in the study. A large-scale
      public health screening study had defined them as people with IGT. The
      participants took part in a semi-structured interview that focused on four
      aspects of everyday lifestyle: (1) structure and rhythm, (2) physical health, (3)
      physical activity and (4) social relations. RESULTS: The interviews showed that
      the participants in the study changed their priorities regarding daily living.
      Results indicated four domains of motivational factors that appeared as
      significant for lifestyle changes. The participants attributed great significance
      to their physical health and were strongly motivated to prevent disease
      development by improvement of everyday structure and rhythm, reduction of
      sickness risk, activity level and social relation. Research indicates, however,
      that lasting lifestyle changes take time and that health care support must be
      adapted to the individual in light of their social setting. CONCLUSION: Persons
      with IGT appear to benefit from lifestyle changes along four dimensions of
      motivational significance: Structure and rhythm, Sickness concerns, Activity
      levels, Social relations. This means that attention needs to be more carefully
      tailored the individual along these four dimensions than has been the case in
      traditional health care.

PMID- 21175732
TI  - Being an outpatient with rheumatoid arthritis--a focus group study on patients'
      self-efficacy and experiences from participation in a short course and one of
      three different outpatient settings.
AB  - BACKGROUND: A Danish study compared three different outpatient settings for
      persons with rheumatoid arthritis (RA). All participants completed a short course
      before random allocation to one of three groups. A third of the patients
      continued with planned medical consultations. A third was allocated to a shared
      care setting with no planned consultations. The final third was allocated for
      planned nursing consultations every 3 months. Little knowledge exists of
      patients' experiences at different outpatient settings. AIMS: (1) To explore the
      patients' experiences of participation in the course and one of the three
      different outpatient settings and (2) to explore whether some of these
      experiences can explain possible changes in self-efficacy beliefs. METHOD: In
      total six focus group interviews were carried out with 33 participants from the
      three settings. The interviews and the analysis were inspired by phenomenological
      philosophy. RESULTS: On the short course the participants felt understood, gained
      new insights and some changed behaviours after attendance. Important themes in
      experiences from the three outpatient settings were: (1) continuity and
      relationships with health professionals, (2) a need for others to take control,
      and (3) contact with health professionals. SPECIFIC FINDINGS: The nursing
      consultations were experienced as less factual and less authoritarian than the
      medical consultations. The participants in the shared care setting had a lack of
      confidence in the GP's competence to manage their RA. However, they felt
      responsible for taking action in case of a flare up. The study provided
      opportunities to enhance the participants' self-efficacy beliefs. CONCLUSION:
      When planning follow-up care, the focus needs to be on continuity, the
      interpersonal relationship and easy access to health professionals with thorough
      knowledge of RA. A short course and consultations with nurses and hospital
      doctors can enhance patients' self-efficacy and thereby strengthen their
      confidence to assess and manage their own disease.

PMID- 21175734
TI  - The incidence and prevalence of Cushing's disease may be higher than previously
      thought: results from a retrospective study in Iceland 1955 through 2009.

PMID- 21175733
TI  - Learning to live with irritabel bowel syndrome. The influence of a group-based
      patient education programme on peoples' ability to manage illness in everyday
      life.
AB  - BACKGROUND: Living with chronic irritable bowel syndrome sets limitations in
      peoples' everyday lives. This is due to bad health and the difficulty to find
      strategies that will manage their problem. In encounters with health care
      providers, these people feel that they are not getting the appropriate support to
      manage their illness-related troubles, and they perceive themselves to be
      insufficiently informed about the disease. AIM: To evaluate the influence of a
      group-based patient education programme about irritable bowel syndrome, on
      people's ability to manage their illness in everyday life. METHODS: The study
      used an evaluative research design. Fifty-one individuals with irritable bowel
      syndrome completed the ways of coping questionnaire, and the irritable bowel
      syndrome severity scoring system, before and after participating in a
      multidisciplinary group-based patient education programme. RESULTS: In the
      participants' self assessments, statistical significances (p > 0.05) were found
      for the mean frequency of efforts used on the coping strategies distancing and
      escape-avoidance. Distancing was used more often after the education programme,
      while escape-avoidance, was used more seldom. The proportional use of the
      strategy self-controlling (relative score) was enhanced after the education
      programme. The participants' overall severity of symptoms was significantly
      reduced after the education programme. The individuals with a clinically
      noteworthy improvement in symptom severity (decrease <= 50) had greater changes
      in relative score values than those that showed a lesser improvement in symptom
      severity. CONCLUSION: Coping patterns were changed and symptoms were scored
      significantly less severe among the participants who participated in the
      education programme. Controlled studies following individuals over a longer
      period are suggested to establish the validity and sustainability of these
      changes, and qualitative interview studies would provide additional understanding
      about the significance of the separate parts of the education programme, and
      about the meaning of the programme to peoples' everyday lives as a whole.

PMID- 21175735
TI  - High prevalence of subclinical hypercortisolism in patients with bilateral
      adrenal incidentalomas: a challenge to management.
AB  - OBJECTIVE: The prevalence of subclinical hypercortisolism (SH) in unilateral
      incidentalomas (UI) has been extensively studied; however, patients with
      bilateral incidentalomas (BI) have not been thoroughly investigated. We therefore
      aimed to describe the characteristics of patients with BI compared to their
      unilateral counterparts. The surgical outcome in a small number of patients is
      reported. DESIGN: Observational retrospective study in a single
      secondary/tertiary centre. PATIENTS: One hundred and seventy-two patients with
      adrenal incidentalomas (41 with BI). MEASUREMENTS: Morning cortisol (F), ACTH,
      dehydroepiandrosterone sulphate (DHEA-S), midnight F, 24-h urine collection for
      cortisol (UFC), low-dose dexamethasone suppression test (LDDST), fasting glucose,
      insulin, and oral glucose tolerance test (OGTT). Primarily, SH was defined as F
      post-LDDST>70 nmol/l and one more abnormality; several diverse cut-offs were also
      examined. RESULTS: No difference was noted in age, body mass index, or prevalence
      of diabetes and impaired glucose tolerance between patients with UI and those
      with BI. Patients with BI had higher F-post-LDDST (119.3 +/- 112.8 vs 54.3 +/-
      71.5 nmol/l, P<0.001) and lower DHEA-S (1.6 +/- 1.5 vs 2.5 +/- 2.3 MUmol/l,
      P=0.003) but similar UFC, ACTH and midnight F levels, compared to UI. SH was
      significantly more prevalent in BI (41.5%vs 12.2%, P<0.001). Fourteen patients
      were operated on; four underwent bilateral interventions. In 10 patients,
      unilateral adrenalectomy on the side of the largest lesion resulted in
      significant improvement in F-post-LDDST (P=0.008) and a decrease in midnight F
      (P=0.015) levels. CONCLUSIONS: Subclinical hypercortisolism is significantly more
      prevalent in bilateral incidentaloma patients, posing great dilemmas for its
      optimum management.

PMID- 21175736
TI  - Designing cobalt chromium removable partial dentures for patients with shortened
      dental arches: a pilot survey.
AB  - The aim of this survey was to investigate the quality of prescription for the
      fabrication of cobalt chromium removable partial dentures (RPDs) that are used to
      extend the shortened dental arches (SDAs). A survey of four commercial dental
      laboratories located in northern England was conducted. The target of this survey
      was cobalt chromium RPDs that were requested to restore SDAs comprising the
      anterior teeth and 2-4 premolars. Dentists' prescriptions were scrutinised, and a
      special data collection form was completed accordingly. A total of 94 dentists'
      prescriptions and associated SDA casts were examined. Almost all the requested
      cobalt chromium RPDs were clasp-retained RPDs (97%). Scrutinising the 91
      prescriptions for clasp-retained cobalt chromium RPDs showed that dentists'
      prescriptions did not have any instructions about the design of the partial
      denture in a considerable proportion of the cases (32%). Teeth to be clasped were
      identified clearly in 45% of the prescriptions. A majority of the dentists (64%)
      failed to provide any instructions about the design of the rests to be placed on
      the most posterior premolar abutment teeth. A considerable proportion of the
      dentists delegated the task of selecting the type of the major connector to the
      dental technician (41%). Only 21 (23%) of the examined casts had clearly defined
      rest seat preparation. The outcome of this pilot survey shows inadequate quality
      of prescription in designing RPDs for patients with SDAs. This finding has an
      ethical and clinical bearing and does not fit with current legal guidelines
      relevant to designing RPDs.

PMID- 21175737
TI  - Role of matrix metalloproteinase-9 (MMP-9) in striatal blood-brain barrier
      disruption in a 3-nitropropionic acid model of Huntington's disease.
AB  - AIMS: 3-Nitropropionic acid (3-NPA) is a natural toxin that, when administered to
      experimental animals, reproduces the brain lesions observed in Huntington's
      disease, which mainly consist of selective neurodegeneration of the striatum. The
      lesions also include severe alterations to the blood-brain barrier (BBB), which
      increase its permeability to several substances including blood components and
      exogenous fluorescent dyes, and the concomitant degradation of some of its
      constituents such as endothelial cells, tight junction proteins and the basement
      membrane. We studied here the role of matrix metalloproteinases (MMPs)-2 and -9,
      also called gelatinases A and B, in the degradation of the BBB in the striatal
      lesions induced by the systemic administration of 3-NPA to Sprague-Dawley rats.
      METHODS: 3-NPA was intraperitoneally administered at a dose of 20 mg/kg once a
      day for 3 days. MMPs were studied by means of immunohistochemistry and in situ
      zymography. RESULTS: In 3-NPA-treated rats, MMP-9 was present in most of the
      degraded blood vessels in the injured striatum, while it was absent in vessels
      from non-injured tissue. In the same animals, MMP-2 staining was barely detected
      close to degraded blood vessels. The combination of MMP-9 immunostaining, in situ
      zymography and inhibitory studies of MMP-9 confirmed that net gelatinolytic
      activity detected in the degraded striatal blood vessels could be attributed
      almost exclusively to the active form of MMP-9. CONCLUSION: Our results highlight
      the prominent role of MMP-9 in BBB disruption in the striatal injured areas of
      this experimental model of Huntington's disease.

PMID- 21175738
TI  - Intracisternal enzyme replacement therapy in lysosomal storage diseases: routes
      of absorption into brain.
AB  - AIMS: The research concerns enzyme replacement therapy in lysosomal storage
      diseases with central nervous system involvement. The principle aim was to
      understand the routes of entry of enzyme into the brain when delivered directly
      into the cerebrospinal fluid (CSF) via the cerebellomedullary cistern. METHODS:
      Pathways for absorption of replacement enzyme were investigated in dogs with
      mucopolysaccharidosis IIIA (MPSIIIA) following intracisternal injections of human
      recombinant N-sulphoglucosamine sulphohydrolase (rhSGSH, EC3.10.1.1) by light and
      confocal microscopy using chromogenic and fluorescent immune probes. RESULTS:
      Enzyme entered the brain superficially by penetration of the pia/glia limitans
      interface, but the main route was perivascular along large veins, arteries and
      arterioles extending onto capillaries. It further dispersed into surrounding
      neuropil to be taken up by neurones, macrophages, astrocytes and oligodendroglia.
      Enzyme also entered the lateral ventricles adjacent to the choroid plexus,
      probably also by the tela choroidea and medullary velum, with further spread
      throughout the ventricular system and spinal canal. There was secondary spread
      back across the ependyma into nervous tissue of brain and spinal cord.
      CONCLUSIONS: Enzyme mainly enters the brain by a perivascular route involving
      both arteries and veins with subsequent spread within the neuropil from where it
      is taken up by a proportion of neurones and other cells. Penetration of enzyme
      through the pia/glia limitans is minor and superficial.

PMID- 21175739
TI  - Prenatal development of the adrenal gland in the one-humped camel (Camelus
      dromedarius).
AB  - With 14 figures and 3 tables SUMMARY: Each adrenal gland consisted of cortex and
      medulla that developed from different embryological origins and presented
      different cellular organization. One hundred male or female camel embryos or
      fetuses with crown vertebral rump lengths (CVRL) that ranged from 0.8 to 117 cm
      were examined. The adrenal cortex, which is derived from intermediate mesoderm,
      was first observed in the 0.8-cm CVRL camel embryo. The adrenal cortex initially
      was combined with the gonad as a thickened region of proliferating cells derived
      from splanchnic intermediate mesoderm. Adrenocortical tissue was first separated
      from the gonadal tissue in the 2-cm CVRL camel fetus and was observed as a
      separate dorso-medial mass of cells. At 2.5-cm CVRL, the adrenocortical tissue
      was surrounded by a capsule of undifferentiated mesenchymal cells, except at its
      proximal pole, where an invagination was located through which chromaffinoblast
      cells entered the cortex. The chromaffinoblast cells migrated from the neural
      crest to form the medulla of the developing adrenal gland. In the 3.5-cm CVRL
      camel fetus, the adrenocortical cells differentiated into two layers: the inner
      fetal cortex and the outer definitive cortex. As development proceeded, the fetal
      cortex degenerated and the definitive cortex formed the zona glomerulosa and zona
      fasciculata. The zona reticularis did not form until the end of gestation. During
      prenatal life, the adrenal medulla was much thicker than the cortex.

PMID- 21175740
TI  - Histochemistry of sialoglycoconjugates in goat submandibular glands.
AB  - The functional properties of sialic acids appear to be manifold. Therefore, they
      are considered as essential components of saliva. In this study, the localization
      of sialoglycoconjugates in the submandibular glands of Japanese miniature (Shiba)
      goat was examined by light and electron microscopic histochemical methods. The
      submandibular glands exhibited a large amount of sialic acids. Additionally,
      sialic acids with O-acetyl substitutions were detectable in the mucous acinar
      cells and serous demilunar cells. According to lectin histochemical methods, the
      mucous and serous cells mainly contained the Siaalpha2-6Gal/GalNAc sequence.
      These sialoglycoconjugates generated by the submandibular glands may specifically
      participate in the maintenance of the viscoelastic properties of saliva,
      protection of oral tissues and prevention of pathogenic microbial attacks.
      Therefore, our results suggest that they are essential components of saliva to
      maintain oral health.

PMID- 21175741
TI  - The yfeR gene of Salmonella enterica serovar Typhimurium encodes an osmoregulated
      LysR-type transcriptional regulator.
AB  - A genetic screening for osmoregulated genes allowed us to identify the yfeR gene
      of Salmonella enterica serovar Typhimurium. The yfeR gene product encodes a novel
      LysR-type transcriptional regulator (LTTR), the expression of which decreases
      when external osmolarity increases. Out of the adjacent gene yfeH, YfeR modulates
      expression of several genes that may be required for optimal growth under low
      osmolarity conditions.

PMID- 21175742
TI  - Detergents enhance EspB secretion from Escherichia coli strains harboring the
      locus for the enterocyte effacement (LEE) gene.
AB  - The effects of detergents (cholic acid, deoxycholic acid, Triton X-100, and
      Nonidet P-40) on the secretion of EspB from the locus for enterocyte effacement
      (LEE) gene-positive Escherichia coli strains were examined. Clinical isolates of
      eight EPEC strains and seven STEC strains were used to detect EspB after they had
      been cultivated in Luria-Bertani (LB) broth containing one of the detergents.
      When the bacteria were cultured in LB broth supplemented with one of the
      detergents, the amount of EspB produced was increased by 2-32-fold depending on
      the detergent and the strain used. EspB was detected in all strains when they
      were cultured in LB broth containing all of the detergents. The results obtained
      in this study can be applied to immunological diagnostic methods for detecting
      EspB and also to the production of EspB for research purposes.

PMID- 21175743
TI  - Control of aerial mycelium formation by the BldK oligopeptide ABC transporter in
      Streptomyces griseus.
AB  - An oligopeptide permease family ATP-binding cassette (ABC) transporter encoded by
      SGR2418-SGR2414 was shown to be essential for aerial mycelium formation on
      glucose-containing media in Streptomyces griseus. In spite of only weak sequence
      similarity, the operon was equivalent to the bldK operon of Streptomyces
      coelicolor A3(2) in terms of chromosomal location and function. Transcription of
      the operon appeared not to be directly regulated by AdpA, a global regulator of
      morphological and physiological development in S. griseus, although it was
      affected by adpA inactivation. This study revealed that an ABC transporter was
      essential for aerial mycelium formation not only in S. coelicolor A3(2) but also
      in S. griseus, indicating that extracellular signaling by certain peptides should
      be conserved among different Streptomyces species.

PMID- 21175744
TI  - Ultrastructural alterations induced by Delta(24(25))-sterol methyltransferase
      inhibitors on Trichomonas vaginalis.
AB  - Trichomonas vaginalis is an important human parasite that causes trichomoniasis,
      a cosmopolitan sexually transmitted disease. Currently, the treatment of choice
      for T. vaginalis infections is metronidazole. The increase in metronidazole
      resistant parasites and undesirable side effects of this drug make the search for
      alternative chemotherapeutic approaches a priority for the management of
      trichomoniasis. Here, the antiproliferative and ultrastructural effects of sterol
      biosynthesis inhibitors against T. vaginalis were investigated. It was found that
      22,26-azasterol (5 MUM) and 24(R,S),25-epiminolanosterol (10 MUM), known
      inhibitors of Delta(24(25))-sterol methyltransferase, exhibited antiproliferative
      effects on T. vaginalis trophozoites cultured in vitro. Morphological analyses
      showed that azasterols induced changes in the ultrastructure of T. vaginalis. The
      most significant alterations were (1) membrane blebbing and disruption, (2)
      wrinkled cells and (3) the formation of cell clusters. In addition, autophagic
      vacuoles, Golgi duplication arrest, an abnormal Golgi enlargement and damaged
      hydrogenosomes were also observed. Nonspecific cytotoxicity assays using the
      cultured mammalian cell lines Madin-Darby canine kidney cells showed no effect of
      the azasterols on the viability and proliferation of these cells at a
      concentration that significantly inhibited the proliferation of T. vaginalis,
      indicating a selective antiparasitic action. Taken together, these results
      suggest that azasterols could be important compounds in the development of novel
      chemotherapeutic approaches against T. vaginalis.

PMID- 21175745
TI  - Subinhibitory concentrations of farrerol reduce alpha-toxin expression in
      Staphylococcus aureus.
AB  - In this study, the antibacterial activity of farrerol against Staphylococcus
      aureus was determined. The minimum inhibitory concentrations capable of
      inhibiting 35 S. aureus strains ranged from 4 to 16 MUg mL(-1) . A haemolysis
      assay, Western blot and real-time reverse transcriptase-PCR assay were performed
      to identify the influence of subinhibitory concentrations of farrerol on the
      secretion of alpha-toxin by S. aureus. The results show that farrerol
      significantly decreased, in a dose-dependent manner, the production of alpha
      toxin by both methicillin-sensitive S. aureus and methicillin-resistant S.
      aureus.

PMID- 21175746
TI  - Lactic acid bacteria fermentation of human milk oligosaccharide components, human
      milk oligosaccharides and galactooligosaccharides.
AB  - Human milk contains about 7% lactose and 1% human milk oligosaccharides (HMOs)
      consisting of lactose with linked fucose, N-acetylglucosamine and sialic acid. In
      infant formula, galactooligosaccharides (GOSs) are added to replace HMOs. This
      study investigated the ability of six strains of lactic acid bacteria (LAB),
      Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus fermentum,
      Lactobacillus reuteri, Streptococcus thermophilus and Leuconostoc mesenteroides
      subsp. cremoris, to digest HMO components, defined HMOs, and GOSs. All strains
      grew on lactose and glucose. N-acetylglucosamine utilization varied between
      strains and was maximal in L. plantarum; fucose utilization was low or absent in
      all strains. Both hetero- and homofermentative LAB utilized N-acetylglucosamine
      via the Embden-Meyerhof pathway. Lactobacillus acidophilus and L. plantarum were
      the most versatile in hydrolysing pNP analogues and the only strains releasing
      mono- and disaccharides from defined HMOs. Whole cells of all six LAB hydrolysed
      oNP-galactoside and pNP-galactoside indicating beta-galactosidase activity. High
      beta-galactosidase activity of L. reuteri, L. fermentum, S. thermophilus and L.
      mesenteroides subsp. cremoris whole cells correlated to lactose and GOS
      hydrolysis. Hydrolysis of lactose and GOSs by heterologously expressed beta
      galactosidases confirmed that LAB beta-galactosidases are involved in GOS
      digestion. In summary, the strains of LAB used were not capable of utilizing
      complex HMOs but metabolized HMO components and GOSs.

PMID- 21175748
TI  - Dermoscopy has opened a new morphological horizon for dermatologists!

PMID- 21175749
TI  - Key points in dermoscopy for diagnosis of melanomas, including difficult to
      diagnose melanomas, on the trunk and extremities.
AB  - Early diagnosis and prompt surgical excision are the most important aims in the
      secondary prevention of cutaneous melanoma. Dermoscopy has increased the accuracy
      in the detection of melanoma because of dermoscopic-specific features that can be
      easily detected by trained dermoscopists. However, the classical melanoma
      specific criteria such as multicomponent pattern, atypical pigmented network,
      irregular dots/globules, irregular streaks, multiple colors, blue-whitish veil or
      regression structures may not be present in all of these lesions. For some early
      melanomas change, as evidenced by sequential dermoscopic monitoring, may be the
      only feature suggesting malignancy. At present, even with dermoscopy, the
      diagnosis of these early melanomas remains to be a challenge for dermatologist.
      Patient education, digital dermoscopic follow up and consensus diagnosis have
      been proposed to overcome this problem.

PMID- 21175750
TI  - Key points in the dermoscopic diagnosis of hypomelanotic melanoma and nodular
      melanoma.
AB  - Nodular melanoma (NM) and amelanotic/hypomelanotic melanoma (AHM) often present a
      challenge to the diagnosing clinician. A significant proportion of AHM are
      nodular in nature. Such tumors may lack features of asymmetry and altered
      peripheral pigmentation routinely observed in other melanoma subtypes. This lack
      of distinguishing clinical features can potentially result in delayed diagnosis
      or inappropriate treatment. This review highlights the key points in evaluating
      the range of lesions where AHM or NM are considered in the differential diagnosis
      and summarizes current evidence in relation to pigmented and vascular dermoscopic
      diagnostic criteria for both.

PMID- 21175751
TI  - What dermoscopy tells us about nevogenesis.
AB  - The evolution of nevi is a complex process involving several constitutional and
      environmental factors. Although histopathology is the gold standard for the
      diagnosis and classification of melanocytic nevi, the widespread use of in vivo
      diagnostic technologies such as dermoscopy and more recently of reflectance
      confocal microscopy, has enriched profoundly our knowledge regarding the
      morphological variability of nevi in different stages of their evolution. In
      addition, significant progress has been made in our understanding of genetic
      alterations and molecular pathways involved in the formation of melanocytic
      tumors. All this newly acquired knowledge increasingly questions whether
      morphologically different nevi are also histiogenetically different. In this
      article, we intend to extract some of the salient points from published clinical
      and molecular studies on melanocytic tumors and attempt to assimilate them into
      an integrative concept of nevogenesis.

PMID- 21175752
TI  - Key points in dermoscopic differentiation between early acral melanoma and acral
      nevus.
AB  - Acral skin is the most prevalent site of malignant melanoma in non-Caucasian
      populations. On acral skin, other various kinds of pigmented lesions are also
      detected. Particularly, melanocytic nevus is commonly seen on acral volar skin;
      approximately 10% of Japanese have a nevus on their soles. Prognosis of acral
      melanoma is still generally poor because of delayed detection in the advanced
      stages. To improve the prognosis, early detection is essential. Early acral
      melanoma is seen as a brownish macule, which is clinically quite similar to acral
      nevus. Therefore, clinicians often face a dilemma when they see a pigmented
      macule on acral volar skin. Introduction of dermoscopy was a great epoch in this
      field. Pigmentation pattern on dermoscopy is completely opposite between early
      acral melanoma and acral nevus; pigmentation on the ridges of the surface skin
      markings is detected in early acral melanoma, whereas pigmentation along the
      furrows of the skin markings is seen in acral nevus. We termed these dermoscopic
      patterns the parallel ridge pattern and the parallel furrow pattern,
      respectively. These features are highly helpful in the differentiation between
      the two biologically distinct entities. The sensitivity and specificity of the
      parallel ridge pattern in diagnosing early acral melanoma is 86% and 99%,
      respectively. However, we must be aware that dermoscopic features in acral nevus
      sometimes mimic the parallel ridge pattern and that other conditions also could
      show dermoscopic features similar to the parallel ridge pattern. In this review
      article, we summarize key points of the dermoscopic diagnosis of early acral
      melanoma and then describe the three-step algorithm for the management of acral
      melanocytic lesions, which surely aids us in effectively detecting early acral
      melanoma and in reducing unnecessary resection of benign nevus.

PMID- 21175753
TI  - Correspondence between dermoscopic features and epidermal structures revealed by
      scanning electron microscope.
AB  - It is already known that some typical dermoscopic patterns seen in melanocytic
      nevi on the sole have their own favorite site. In the weight-bearing area,
      melanocytic nevi with a parallel furrow pattern were preferentially observed.
      Those with a lattice-like pattern were observed in the arch area, whereas those
      with a crista reticulated pattern were seen in the border area. To investigate
      the relationship between the distribution of the dermoscopic patterns seen in
      plantar melanocytic nevi and the 3-D structures of the epidermis, the basal
      surfaces of the plantar epidermis from 14 skin lesions were observed by scanning
      electron microscopy (SEM). Our SEM observations revealed that transverse ridges
      formed a couple of parallel lamellae on the crista profunda limitans (limiting
      ridges). Between the limiting ridges and the crista profunda intermedia
      (intermediate ridges), the transverse ridges had different shapes according to
      the anatomical location of the sole. From these results, it was suggested that
      the characteristic dermoscopic patterns seen in acquired and junctional
      melanocytic nevi on the sole simulate the arrangement of transverse ridges.

PMID- 21175754
TI  - Benign acral lesions showing parallel ridge pattern on dermoscopy.
AB  - One of the recent advances in dermoscopy is the significance of parallel ridge
      pattern (PRP), which has 99% specificity in detecting both melanoma in situ and
      advanced melanoma on the acral volar skin. This review features exceptionally
      benign acral lesions showing PRP on dermoscopy. These benign lesions can be
      distinguished from malignant melanoma, because of the typical clinical history
      and associated symptoms. However, it is sometimes difficult for dermatologists to
      exclude malignant melanoma and a subsequent skin biopsy should be strongly
      recommended. These benign lesions include pigmentation due to a dye such as para
      phenylenediamine, acral pigmented macules associated with Peutz-Jeghers syndrome,
      anti-cancer drug-induced hyperpigmentation on the volar skin, acral subcorneal
      hemorrhage and pigmented warts.

PMID- 21175755
TI  - Key point in dermoscopic differentiation between early nail apparatus melanoma
      and benign longitudinal melanonychia.
AB  - Longitudinal melanonychia presents in various conditions including neoplastic and
      reactive disorders. It is much more frequently seen in non-Caucasians than
      Caucasians. While most cases of nail apparatus melanoma start as longitudinal
      melanonychia, melanocytic nevi of the nail apparatus also typically accompany
      longitudinal melanonychia. Identifying the suspicious longitudinal melanonychia
      is therefore an important task for dermatologists. Dermoscopy provides useful
      information for making this decision. The most suspicious dermoscopic feature of
      early nail apparatus melanoma is irregular lines on a brown background.
      Evaluation of the irregularity may be rather subjective, but through experience,
      dermatologists can improve their diagnostic skills of longitudinal melanonychia,
      including benign conditions showing regular lines. Other important dermoscopic
      features of early nail apparatus melanoma are micro-Hutchinson's sign, a wide
      pigmented band, and triangular pigmentation on the nail plate. Although there is
      as yet no solid evidence concerning the frequency of dermoscopic follow up, we
      recommend checking the suspicious longitudinal melanonychia every 6 months.
      Moreover, patients with longitudinal melanonychia should be asked to return to
      the clinic quickly if the lesion shows obvious changes. Diagnosis of amelanotic
      or hypomelanotic melanoma affecting the nail apparatus is also challenging, but
      melanoma should be highly suspected if remnants of melanin granules are detected
      dermoscopically.

PMID- 21175756
TI  - Key points in dermoscopic differentiation between lentigo maligna and solar
      lentigo.
AB  - A clinical diagnosis of lentigo maligna at an early stage is often difficult even
      for experienced dermatologists. Differential diagnoses would include solar
      lentigo, early lesions of seborrheic keratosis, lichen planus-like keratosis,
      pigmented actinic keratosis and melanocytic nevus. Dermoscopy has been shown to
      have higher diagnostic accuracy, especially in the diagnosis of pigmented skin
      lesions, in the past two decades. To aim of the present study was to review the
      diagnostic key points on dermoscopy in the published work to differentiate
      lentigo maligna from other differential diagnoses and reassess these important
      features on dermoscopy for specificity by describing the findings in detail.
      Diagnostic key points for lentigo maligna/lentigo maligna melanoma on dermoscopy
      are asymmetrical pigmented follicular openings, rhomboidal structures, annular
      granular structures and gray pseudo-network. Lentigo maligna, at first, seems to
      occur as asymmetrical pigmented follicular openings and/or annular-granular
      structures, then expand and develop into the rhomboidal structures. Annular
      granular structures and gray pseudo-network seem to be observed also in
      regressive areas of solar lentigo/initial seborrheic keratosis, lichen planus
      like keratosis and pigmented actinic keratosis. The four important criteria on
      dermoscopy for the diagnosis of lentigo maligna have been reviewed, and the
      former two criteria seem to be more specific, but it might be difficult to
      recognize these findings without misinterpretation. The latter two seem to be not
      so specific as they would also be demonstrated in other pigmented epidermal
      lesions, although the distribution of the structures in these disorders would be
      inclined to be more homogeneous than that of lentigo maligna.

PMID- 21175757
TI  - Key points in dermoscopic diagnosis of basal cell carcinoma and seborrheic
      keratosis in Japanese.
AB  - Basal cell carcinoma (BCC) and seborrheic keratosis (SK) are representative
      pigmented skin tumors, and they are differentiated as non-melanocytic lesions in
      the two-step dermoscopy algorithm proposed by the Consensus Net Meeting on
      Dermoscopy. Because most BCC in Japanese patients are pigmented clinically,
      dermoscopy plays an important role in their differential diagnosis. The
      dermoscopic criteria for BCC include the lack of a pigment network and the
      presence of at least one positive feature for BCC, such as large blue-gray ovoid
      nests, multiple blue-gray globules, leaf-like areas, spoke wheel areas,
      arborizing vessels and ulceration. Whereas various dermoscopic features are seen
      in SK, comedo-like openings, milia-like cysts, and fissures and ridges are
      especially important features. It is necessary for clinicians to consider the
      pathological conditions causing the dermoscopic features of BCC and SK. In
      addition, the sensitivity and specificity of each feature should be taken into
      consideration to ensure an accurate dermoscopic diagnosis.

PMID- 21175758
TI  - Dermoscopy findings of nail fold capillaries in connective tissue diseases.
AB  - Nail fold (video) capillaroscopy is a well-established technique to assess
      patients with Raynaud's phenomenon, in whom specific abnormalities of capillaries
      are predictive of underlying systemic sclerosis and its related diseases
      (scleroderma spectrum disorder). The typical abnormalities are also found in
      patients with dermatomyositis and those findings are useful for the assessment of
      vascular injury and the evaluation of therapeutic effect in patients with
      scleroderma spectrum disorder and dermatomyositis. Recently, it has been
      suggested that dermoscopy can replace the capillaroscopy in significant part for
      detection of nail fold capillary abnormalities. In this review, I summarized the
      established capillaroscopy findings in connective tissues diseases and tried to
      apply the findings of dermoscopy to the findings and classification of
      capillaroscopy.

PMID- 21175759
TI  - Trichoscopy for common hair loss diseases: algorithmic method for diagnosis.
AB  - In recent years, the usefulness of trichoscopy (scalp dermoscopy) has been
      reported for hair loss diseases. Here, characteristic trichoscopic features of
      common hair loss diseases are described using a DermLite II pro or Epilight
      eight. Characteristic trichoscopic features of alopecia areata are black dots,
      tapering hairs (exclamation mark hairs), broken hairs, yellow dots and short
      vellus hairs. In androgenetic alopecia (AGA), hair diameter diversity (HDD),
      perifollicular pigmentation/peripilar sign and yellow dots are trichoscopically
      observed. In all cases of AGA and female AGA, HDD more than 20%, which
      corresponds to vellus transformation, can be seen. In cicatricial alopecia (CA),
      the loss of orifices, a hallmark of CA, and the associated changes including
      perifollicular erythema or scale and hair tufting were observed. Finally, an
      algorithmic method for trichoscopic diagnosing is proposed.

PMID- 21175760
TI  - Clinicopathological significance of sentinel node biopsy in Japanese patients
      with cutaneous malignant melanoma.
AB  - Sentinel node biopsy (SNB) for malignant melanoma began to be performed in our
      department in 1997. A total of 121 patients underwent SNB. Sentinel node (SN)
      were identified in 39 (83.0%) of the 47 cases in which the blue dye method alone
      was used, and in 71 (95.9%) of the 74 cases by combination of dye, radioisotope,
      and gamma probe methods. The excised SN was cut through its longest meridian, and
      the cut surfaces were stained with hematoxylin and eosin (HE) and examined for
      the presence (SN(+) ) or absence (SN(-) ) of melanoma cells. If no melanoma cells
      were detected, serial sections were prepared and examined by sequential staining
      with HE, for S-100 protein, with HE, for HMB-45, with HE, and for Melan-A. In
      this study minute metastasis (SNm(+) ) was defined as tumor cells newly
      identified in the immunostained section. The thickness of tumors ranged 0-38.0
      mm, and their mean thickness was 4.5 mm. There were 39 SN(+) cases (39/110
      [39+71]; 35.5%) and seven SNm(+) cases (7/110 [39+71]; 6.4%). The 5-year survival
      rate was significantly higher in the SN(-) group than in the SN(+) group and
      SNm(+) group combined (P=0.0002). The survival rate of the SNm(+) group was not
      significantly different from that of the SN(+) group (P=0.3848). The 5-year
      survival rate of the SN(+) group and SNm(+) group combined was significantly
      higher than that of the group with clinically unequivocal metastatic nodes
      (P=0.0001). Accurate SNB results will provide important prognostic information
      for Japanese patients with melanoma.

PMID- 21175761
TI  - Juvenile xanthogranuloma on the sole: dermoscopic findings as a diagnostic clue.

PMID- 21175762
TI  - Dermoscopic features in Laugier-Hunziker syndrome.

PMID- 21175763
TI  - Dermoscopic features in a case of dyschromatosis symmetrica hereditaria.

PMID- 21175764
TI  - Basal cell carcinoma arising on the palm.

PMID- 21175765
TI  - Vulvar basal cell carcinoma with bone metastasis.

PMID- 21175766
TI  - Amalgam tattoo of the oral mucosa mimics malignant melanoma.

PMID- 21175767
TI  - Increased glucose uptake by seborrheic keratosis detected by positron emission
      tomography.

PMID- 21175768
TI  - Autophagy basics.
AB  - Autophagy (macroautophagy) is a dynamic process for degradation of cytosolic
      components. Autophagy has intracellular anti-viral and anti-bacterial functions,
      and plays a role in the initiation of innate and adaptive immune system responses
      to viral and bacterial infections. Some viruses encode virulence factors for
      blocking autophagy, whereas others utilize some autophagy components for their
      intracellular growth or cellular budding. The "core" autophagy-related (Atg)
      complexes in mammals are ULK1 protein kinase, Atg9-WIPI-1 and Vps34-beclin1 class
      III PI3-kinase complexes, and the Atg12 and LC3 conjugation systems. In addition,
      PI(3)-binding proteins, PI3-phosphatases, and Rab proteins contribute to
      autophagy. The autophagy process consists of continuous dynamic membrane
      formation and fusion. In this review, the relationships between these Atg
      complexes and each process are described. Finally, the critical points for
      monitoring autophagy, including the use of GFP-LC3 and GFP-Atg5, are discussed.

PMID- 21175769
TI  - Assembly of hepatitis C virus particles.
AB  - Infection with hepatitis C virus (HCV) is a major risk factor for chronic
      hepatitis, cirrhosis and hepatocellular carcinoma. Once robust cell culture
      systems for production of recombinant infectious HCV became available, evidence
      on molecular mechanisms underlying assembly and release of the virus particles
      began to accumulate. Recent studies have demonstrated that lipid droplets and
      viral nonstructural proteins play key roles in HCV morphogenesis. This review
      considers the current knowledge about maturation of HCV structural proteins and
      production of viral infectious particles.

PMID- 21175770
TI  - Development of a cytotoxic T-lymphocyte-based, broadly protective influenza
      vaccine.
AB  - The current vaccination strategy against influenza is to induce production of
      antibodies directed against the surface antigens of these viruses. However,
      frequent changes in the surface antigens of influenza viruses allow them to avoid
      antibody-mediated immunity. On the other hand, it is known that cytotoxic T
      lymphocyte (CTL) populations directed against internal antigens of influenza A
      virus are broadly cross-reactive to influenza virus subtypes. The present authors
      have previously demonstrated that antigens chemically coupled to the surface of
      liposomes made using unsaturated fatty acids are cross-presented by APCs via MHC
      class I to CD8(+) T cells and induce antigen-specific CTLs. Based on this
      finding, a liposome vaccine that is capable of inducing CTL response against
      internal antigens of influenza viruses and removing virus-infected cells in the
      host has been developed. The CTL-based liposomal technique might be applicable
      for developing vaccines against influenza and other viruses, such as hepatitis C,
      HIV, and severe acute respiratory syndrome corona virus, which frequently change
      their surface antigenic molecules.

PMID- 21175771
TI  - A combination of methods to evaluate biofilm production may help to determine the
      clinical relevance of Staphylococcus in blood cultures.
AB  - Staphylococcus is the most prevalent pathogen causing bacteremia and many of its
      isolates possess the ability to form biofilm. In this study Staphylococcus
      isolates from the blood of patients with bacteremia were analyzed by two biofilm
      detection phenotypic methods: Congo red agar (CRA) and microtiter-plate adherence
      (MPA) in relation to the presence of ica genes, detected by PCR. Their oxacillin
      susceptibility was also evaluated. Among 127 isolates evaluated, 47 were S.
      aureus and 80 were coagulase negative staphylococci (CNS). Seventy-four (58.3%)
      isolates were mecA gene positive (27.7%S. aureus and 76.3% CNS isolates). Among
      the 40 S. aureus isolates which were positive for the ica genes, 25 (62.5%) were
      positive in MPA and 27 (67.5%) in CRA, whereas both methods combined detected 34
      (85%) isolates as biofilm producers. Among 12 S. epidermidis isolates carrying
      ica genes, 8 were positive in MPA and 5 in CRA. The combination of CRA and MPA
      methods provided a better prediction of the presence of ica genes in S. aureus
      isolates than did either method alone.

PMID- 21175772
TI  - Insights into a nonhomologous integration pathway in the dermatophyte
      Trichophyton mentagrophytes: efficient targeted gene disruption by use of mutants
      lacking ligase IV.
AB  - Targeted gene disruption experiments in Trichophyton mentagrophytes are impeded
      by the dominant of repair of DNA double strand breaks through a nonhomologous end
      joining pathway (NHEJ). Inactivation of human DNA ligase IV homologs, which is
      involved in the final step of the NHEJ pathway, has been shown to enhance
      homologous recombination (HR) frequency in filamentous fungi. To improve the
      frequency of HR in T. mentagrophytes, the lig4 homolog (TmLIG4) was disrupted. T.
      mentagrophytes lacking TmLIG4 showed no discernable phenotypic differences when
      compared to wild-type controls. Both mutant and parent strains had almost
      identical growth ability, sporulation rate and sensitivity to DNA damaging
      agents. When four different loci were disrupted in the TMLIG4-deficient mutant,
      HR frequencies reached as high as 93% depending on the locus, whereas they ranged
      from 0%-40% in the wild-type. These results suggest that studies in strains
      lacking TmLIG4 would help to improve our understanding of dermatophytosis by
      facilitating the genetic manipulation of dermatophytes.

PMID- 21175773
TI  - Rapid detection of Lassa virus by reverse transcription-loop-mediated isothermal
      amplification.
AB  - In this study, a simple one-step reverse transcription-loop-mediated isothermal
      amplification (RT-LAMP) assay for rapid detection of Lassa virus (LASV) was
      established. The two primer sets were designed to detect LASV circulating in
      Sierra Leone and northeastern Nigeria. The RT-LAMP assay using these primer sets
      was able to detect 100 copies of the in vitro transcribed artificial LASV RNA
      within 25 min. The assay was also evaluated using intact viral RNA extracted from
      cell culture-propagated viruses and confirmed to be highly specific for LASV. The
      RT-LAMP assay developed in this study is rapid, simple, and highly specific for
      the detection of LASV, although its sensitivity is slightly lower than that of
      real-time RT-PCR. In addition, because the RT-LAMP assay does not require the use
      of sophisticated equipment, it would be advantageous for clinical diagnosis of
      LASV infection in developing countries. It might also be employed in cases of
      deliberate release during bioterrorism attacks or in epidemiological surveillance
      for disease outbreaks.

PMID- 21175774
TI  - Hepatitis B virus surface antigen can activate dendritic cells and modulate T
      helper type immune response.
AB  - Hepatitis B virus surface antigen (HBsAg) is a major antigen of hepatitis B virus
      (HBV). Dendritic cells (DC) of HBV carriers have been reported to exhibit
      functional impairment. In this study, the role of HBsAg on mice bone marrow
      derived dendritic cells and immune responses in vivo was studied. The immune
      modulatory function of HBsAg was explored by using mice bone marrow-derived
      dendritic cells in vitro and also by examining an ovalbumin (OVA) specific immune
      response in vivo. Treatment of dendritic cells with HBsAg resulted in enhanced
      cell surface expression of cluster of differentiation (CD) 80, CD83, CD86, and
      major histocompatibility complex (MHC) class II, and enhanced production of
      interleukin (IL)-12 p40 and IL-12 p70. Treatment of dendritic cells with HBsAg
      resulted in decreased T cell secretion of IL-5 by OVA stimulation. In addition,
      the results showed stronger OVA-specific immunoglobulin (Ig) M and weaker IgG
      responses in mice sera when they had been immunized with OVA and co-injected with
      HBsAg. It was also found that the mice exhibited significant enhancement of anti
      OVA IgG2a antibody (Ab), as well as marked inhibition of IgG1 Ab production. In
      cellular immune responses, IL-5 production was significantly decreased and
      interferon (IFN)-gamma increased in the group co-injected with HBsAg. On the
      other hand, the induction of lymphoproliferative response to OVA stimulation in
      spleen cells was decreased in the HBsAg co-injected group. These results
      demonstrate that HBsAg can affect the differentiation of T helper (Th) cells,
      which might provide a strategy for improving its prophylactic and therapeutic
      efficacy.

PMID- 21175775
TI  - Inhibition of biosynthesis of metalloprotease of Aeromonas sobria by sodium
      chloride in the medium.
AB  - The present authors have previously shown that the serine protease activity of
      Aeromonas sobria is markedly decreased when A. sobria is cultured in medium
      containing 3.0% sodium chloride (NaCl, concentration almost equivalent to sea
      water salinity), and that this occurs because, although the synthesis of ASP is
      not disturbed by the salt in the medium, the maturation pathway of serine
      protease of A. sobria (ASP) does not proceed successfully in such a medium. In
      this study, the effect of salt in the medium on the production of metalloprotease
      by A. sobria (AMP) was examined. A. sobria produced AMP in the milieu when the
      bacteria were cultured in medium containing (NaCl) at a concentration of 0.5%.
      However, AMP was not produced when the bacteria were cultured in salty medium
      containing 1.5% or more NaCl. To examine how NaCl reduces the production of
      metalloprotease by A. sobria, the amount of amp mRNA in the cell was measured and
      it was found that this decreased in proportion to the concentration of NaCl in
      the medium. The mRNA of amp was not detected in cells cultured in medium
      containing 1.5% or more NaCl. This means that the transcription of amp is
      inhibited in salty condition. As described, NaCl in the medium disturbs the
      maturation pathway of ASP. The mode of action whereby NaCl suppresses AMP
      activity in A. sobria differs from the mechanism for suppressing ASP activity.

PMID- 21175776
TI  - Detection and identification of non-Candida albicans species in human oral lichen
      planus.
AB  - Candida species were detected and identified in samples from the buccal mucosa,
      dorsal surface of the tongue and supragingival plaque of subjects with oral
      lichen planus (OLP). The Candida in the samples were cultured on selection agars,
      and identified by sequence analyses of 18S, 5.8S and 25/28S rRNA. The isolation
      frequency of Candida was higher in subjects with OLP than in those with healthy
      oral mucosa. Non-C. albicans were only isolated from people with OLP. These
      results support the notion that subjects with OLP are more likely to have oral
      colonization with Candida, and that non-C. albicans are specifically present in
      subjects with this condition.

PMID- 21175777
TI  - Ostial left main stenosis due to takayasu arteritis: multimodality imaging and
      surgical ostioplasty.
AB  - Takayasu's arteritis is an inflammatory process, involving larger blood vessels
      namely the aorta and its branches. The majority of these patients present with
      symptoms of vascular obstruction. We report a case of a 38-year-old Chinese
      female who presented with one month history of angina pectoris as the initial
      manifestation. Coronary angiography showed 99% ostial left main coronary
      stenosis. The diagnosis was first suspected in the operating room by TEE and
      subsequently supported by laboratory studies and aortic biopsy. The technique of
      myocardial revascularization was altered and she underwent patch ostioplasty of
      the left main coronary artery and aortic valve repair to correct aortic
      regurgitation.

PMID- 21175778
TI  - Impaired transport function of the left atrium in patients with lone paroxysmal
      atrial fibrillation.
AB  - BACKGROUND: Although lone paroxysmal atrial fibrillation (LPAF) is clinically
      defined as an arrhythmia that occurs in the absence of structural heart disease,
      it has been suggested that the presence of anatomical substrate is related to
      LPAF. The aim of the present study is to determine whether structural and
      functional remodeling of the left atrium (LA) occurs in patients with LPAF, and
      to identify whether frequent episodes of atrial fibrillation (AF) contribute to
      LA remodeling. METHODS AND RESULTS: Forty-five patients who diagnosed as LPAF and
      age-, gender-, and body mass index-matched healthy control subjects (n = 45) were
      enrolled. Patients were grouped based on the frequency of AF episodes. An
      echocardiography was performed >2 weeks after last episode of AF without
      antiarrhythmic drugs. There were no statistical differences in left ventricular
      (LV) diastolic and systolic functions as well as baseline characteristics between
      patients and controls, whereas, patients had significantly larger LA volume
      (LAV), lower active LA emptying fraction (LAEF(active) , P = 0.009) and total
      LAEF (LAEF(total) , P = 0.005) compared with controls. Passive LAEF
      (LAEF(passive) ) was not different between patients and controls (P = 0.664).
      LAEF(active) was significantly depressed in patients with frequent episodes of AF
      than the others (P = 0.034). CONCLUSIONS: Compared with healthy controls,
      patients with LPAF had increased LAV and depressed LAEF(active) and LAEF(total)
      without accompanying compensatory increase in LAEF(passive) . LAEF(active) was
      influenced by frequent episodes of AF. These findings may support the hypothesis
      that LPAF is "not-so-lone AF" and related to the concealed cardiac dysfunctions.

PMID- 21175779
TI  - Short-axis 2D strain from speckle tracking predicts echocardiographic response to
      cardiac resynchronization therapy.
AB  - AIMS: Two-dimensional (2D) strain imaging from speckle tracking is a Doppler
      independent technique allowing assessment of left ventricular (LV) strain (E);
      systolic strain rate (SRs') and early diastolic strain rate (SRe') in the radial
      and circumferential planes. We set out to investigate whether (i) these
      parameters facilitated assessment of dyssynchronous contraction and (ii) these
      measures could predict response to cardiac resynchronization therapy (CRT).
      METHODS AND RESULTS: Forty-one patients with severe, symptomatic heart failure on
      optimal medical therapy were recruited. Thirty-two healthy subjects were used as
      controls. Time to peak E, SRs', and SRe' of 6 LV segments were measured in the
      parasternal short axis prior to and 6 weeks post CRT implantation. Time delays
      between segments were then calculated and ANOVA assessed for prediction of
      response, classified as reduction in LV end systolic volume of >15%. 2D strain
      demonstrated significantly more dyssynchronous contraction in the heart failure
      population at baseline compared to healthy controls. Significant reduction in
      dyssynchrony was seen in E and SRs' following CRT, largely confined to those with
      evidence of remodeling. The time delay between peak circumferential SRs' of
      opposing walls was the best predictor of reverse remodeling. CONCLUSION: 2D
      strain imaging appears to be a useful measure to predict response to CRT. The
      time to peak circumferential SR is a new predictor of response.

PMID- 21175780
TI  - Right atrial size relates to right ventricular end-diastolic pressure in an adult
      population with congenital heart disease.
AB  - AIM: Noninvasive markers of right ventricular (RV) diastolic dysfunction are
      limited by their lack of reproducibility and accuracy. We tested the hypothesis
      that right atrial (RA) size measured by echocardiography was correlated to
      invasive parameters of RV diastolic filling. METHODS AND RESULTS: We studied 31
      consecutive adult patients with congenital heart disease. From 2D
      echocardiography images, we measured maximal RA long-axis and short-axis lengths,
      area and volume. We compared each of these measures to right ventricular end
      diastolic pressure (RVEDP) and mean right atrial pressure (mRAP) measured by
      right heart catheterization. RA long-axis, short-axis, area, and volume
      correlated significantly with RVEDP (r = 0.78, P < 0.001; r = 0.61, P < 0.001; r
      = 0.79, P < 0.001; and r = 0.75, P < 0.001, respectively) and mRAP (r = 0.66, P <
      0.001; r = 0.56, P = 0.002; r = 0.70, P < 0.001; r = 0.68, P < 0.001,
      respectively). Single cut points for each echocardiographic parameter
      demonstrated reasonable accuracy to rule-in and rule-out RVEDP >= 7 mm Hg
      (sensitivity = 74%, specificity = 82%, positive LR = 4.1, negative LR = 0.32 for
      RA long-axis of 49 mm; sensitivity = 89%, specificity = 82%, positive LR = 4.9,
      negative LR = 0.12 for RA area of 14 cm2; sensitivity = 89%, specificity = 82%,
      positive LR = 4.9, negative LR = 0.13 for RA volume of 37 mL). CONCLUSION: RA
      size measured by echocardiography is strongly correlated to invasive parameters
      of RV diastolic filling and predicts high RV end-diastolic pressure.

PMID- 21175781
TI  - RT-3D TEE: characteristics of mitral annulus using mitral valve quantification
      (MVQ) program.
AB  - AIM: To evaluate the mitral annulus characteristics in significant mitral
      regurgitant lesions using mitral valve quantification (MVQ) program. METHODS: We
      examined 117 patients (39 women), aged 18-86. Patients were separated into four
      subgroups: 35 patients with ischemic mitral regurgitation, 42 patients with
      isolated prolapse of the mitral valve, 12 patients with Barlow disease, and 28
      healthy controls. Mitral annulus was examined in end-systole. The following
      parameters were assessed: anteroposterior and intercommissural diameter,
      perimeter of annulus, area of minimal surface spanning annulus and height of the
      mitral annulus. A new parameter--mitral annulus height index
      (height/circumference * 100) was introduced. Values of these parameters in
      subgroups with mitral pathology were compared with corresponding parameters of
      control group using Student t-test. RESULTS: In subgroups with mitral pathology
      all parameters except mitral annulus height and mitral annulus height index were
      significantly higher than those in the control group. Mitral annulus height was
      significantly higher in Barlow disease, significantly lower in mitral prolapse
      group and comparable to normal controls in the ischemic regurgitation group.
      Mitral annulus height index was significantly higher in Barlow disease and
      significantly lower in patients with prolapse and ischemic regurgitation.
      CONCLUSIONS: Barlow disease is characterized by dilation and vertical deformation
      of the mitral annulus (annulus height and height index increase). Prolapse of the
      mitral valve and ischemic regurgitation of mitral annulus involve dilation and
      flattening of the annulus (annulus height decreases in prolapse group
      significantly, in ischemic regurgitation nonsignificantly, while annulus height
      index decreases significantly in both subgroups).

PMID- 21175785
TI  - Liver transplantation for fulminant hepatic failure: as early as necessary and as
      late as possible.

PMID- 21175786
TI  - Angiogenesis blockade as therapy for hepatocellular carcinoma: progress and
      challenges.

PMID- 21175787
TI  - JGH Foundation emerging leadership lecture. Significance of hepatitis B virus
      genotypes and mutations in the development of hepatocellular carcinoma in Asia.
AB  - Advances in molecular biology technology in the last two decades have allowed
      detailed study of the viral mutations and genomic heterogeneity of hepatitis B
      virus (HBV). The first mutant discovered was precore stop codon mutation. It was
      reported in HBeAg-negative patients and initially thought to associate with
      fulminant hepatitis. Subsequent studies have suggested that it is merely one of
      the mechanisms of losing HBeAg by the virus. Another mutation that can
      downregulate the production of HBeAg is the basal core promoter mutation, which
      is located in the X gene upstream of the precore region. Based on the
      configuration of codon 15 and the stability of the epsilon of the precore region,
      these two mutants will be differentially selected during the course of HBeAg
      seroconversion. The most common HBV genotypes in South-East Asia are genotype B
      and C HBV. The higher hepatocellular carcinoma (HCC) risk of genotype C HBV has
      been confirmed by longitudinal studies in Hong Kong and Taiwan. One possible
      carcinogenic mechanism is its association with basal core promoter mutation,
      which has also been found to be a risk factor of HCC. Within genotype C HBV,
      subgenotype Cs is predominant in South-East Asia and subgenotype Ce is
      predominant in East Asia. Subgenotype Ce HBV has been found to have the highest
      risk of HCC as compared with subgenotype Cs or genotype B HBV. The understanding
      of the carcinogenic mechanisms of these HBV strains may shed light into future
      therapeutics in the prevention and treatment of HBV-related HCC.

PMID- 21175788
TI  - Animal model for study of human hepatitis viruses.
AB  - Human hepatitis B virus (HBV) and hepatitis C virus (HCV) infect only chimpanzees
      and humans. Analysis of both viruses has long been hampered by the absence of a
      small animal model. The recent development of human hepatocyte chimeric mice has
      enabled us to carry out studies on viral replication and cellular changes induced
      by replication of human hepatitis viruses. Various therapeutic agents have also
      been tested using this model. In the present review, we summarize published
      studies using chimeric mice and discuss the merits and shortcomings of this
      model.

PMID- 21175789
TI  - Epigenetic regulation of signaling pathways in cancer: role of the histone
      methyltransferase EZH2.
AB  - EZH2 is the histone H3 lysine 27 methyltransferase of polycomb-repressive complex
      2. It transcriptionally silences cohorts of developmental regulators in
      stem/progenitors and cancer cells. EZH2 is essential in maintaining stem cell
      identity by globally repressing differentiation programs. Analogously, it plays a
      key role in oncogenesis by targeting signaling molecules that control cell
      differentiation. Emerging data indicate that EZH2 promotes cancer formation and
      progression through epigenetic activation of oncogenic signaling cascades and
      inhibition of pro-differentiation pathways. Genome-wide mapping analysis has been
      expanding the repertoire of target genes and the associated signaling pathways
      regulated by EZH2. Better understanding of the molecular basis of such
      regulations in various cancer types will help establish EZH2-mediated epigenetic
      silencing as a therapeutic target.

PMID- 21175790
TI  - Systematic review of hepatocellular adenoma in China and other regions.
AB  - Hepatocellular adenoma (HCA) is a benign liver neoplasm with a risk of
      spontaneous bleeding and malignant transformation. The aim of this review article
      is to review all the case reports and case series of patients with HCA from 1998
      to 2008 in China and other parts of the world in order to compare clinical
      presentation, surgical management and outcomes. A search for all reports of HCA
      in the world literature from 1998 to 2008 was performed. A total of 356 patients
      were identified, including 191 patients from China, 104 from Europe, 46 from
      North America, and 15 from South-East Asia. A female predominance was not
      observed in Chinese patients in contrast to the other regions. Acute/chronic
      abdominal pain was the main clinical presentation in all regions. Twenty patients
      were diagnosed with coexistent hepatocellular carcinoma (HCC), and hepatitis B
      virus infection (HBV) was found among six of them. The management of HCA
      consisted of resection in most cases. The clinical presentation of HCA in China
      differed from other parts of the world regarding male predominance and a higher
      incidence of coexistent HCC in China. This might be the result of the birth
      control policy in China, limited oral contraceptive use, and the higher incidence
      of HBV.

PMID- 21175791
TI  - Topical agents for idiopathic distal colitis and proctitis.
AB  - Rectally administered topical agents have demonstrated efficacy in the
      maintenance of distal colitis (DC) and proctitis and as they are rarely
      associated with significant blood drug levels, side effects are infrequent. The
      topical 5-aminosalicylic acid (5-ASA) suppositories and enemas target different
      regions of the distal colon and are effective for proctitis and DC, respectively.
      They demonstrate clinical results that are better than oral 5-ASAs and are
      preferred to topical steroids with better clinical, endoscopic and histological
      outcomes, without the risk of adrenal suppression. Disease resistant to topical
      agents, however, can be extremely difficult to manage. The addition of oral
      5ASAs, steroids, immunosuppressants and the anti-tumor necrosis factor-alpha
      agents may be effective, but can result in significant side effects and not all
      patients will respond to the therapies. It is for these patients that new and
      novel therapies are required. Novel topical agents have been proposed for the
      management of resistant DC. These agents included butyrate, cyclosporine, and
      nicotine enemas, as well as tacrolimus suppositories, and tacrolimus, ecabet
      sodium, arsenic, lidocaine, bismuth, rebamipide and thromboxane enemas. While
      some of these agents appear to demonstrate impressive outcomes, the majority have
      only been examined in small open-labeled studies. There is thus a desperate need
      for more randomized double-blinded placebo controlled studies to investigate the
      clinical utility of these topical therapies. This review summarizes the efficacy
      of the established topical therapies, and explores the available data on the new
      and novel topical agents for the management of DC and proctitis.

PMID- 21175792
TI  - Effects of multistrain probiotic-containing yogurt on second-line triple therapy
      for Helicobacter pylori infection.
AB  - BACKGROUND AND AIMS: The adjuvant effects of probiotic-containing yogurt on
      second-line triple therapy for Helicobacter pylori (H. pylori) infection have not
      been evaluated. METHODS: A total of 337 patients with persistent H. pylori
      infection, after first-line triple therapy, were randomly assigned to receive
      either triple therapy with (yogurt group, n=151) or without (control group,
      n=186) Will yogurt. Triple therapy consisted of 400 mg moxifloxacin q.d., 1000 mg
      amoxicillin b.i.d., and 20 mg esomeprazole b.i.d. for 14 days. Will yogurt
      contains Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium longum,
      and Streptococcus thermophilus. H. pylori eradication was evaluated by the (13)C
      urea breath test, histology, or the rapid urease test. RESULTS: The eradication
      rates by intention-to-treat analysis were 66.7% and 68.9% in the control and
      yogurt groups, respectively (P=0.667). The eradication rates by per-protocol
      analysis were 78.5% and 86% in the control and the yogurt groups, respectively
      (P=0.110). The adverse event rates were 25.3% and 28.5% in the control group and
      yogurt group, respectively (P=0.508). CONCLUSIONS: The addition of yogurt
      containing probiotics to moxifloxacin-containing second-line treatment neither
      improved H. pylori eradication rates nor reduced the adverse events of treatment.

PMID- 21175793
TI  - Allopurinol might improve response to azathioprine and 6-mercaptopurine by
      correcting an unfavorable metabolite ratio.
AB  - BACKGROUND AND AIM: Allopurinol potentiates azathioprine and 6-mercaptopurine (6
      MP) by increasing 6-thioguanine nucleotide (6-TGN) metabolite concentrations. The
      outcome might also be improved by adding allopurinol in individuals who
      preferentially produce 6-methylmercaptopurine nucleotides (6-MMPN), rather than 6
      TGN. The aim of the present study was to investigate the effect of allopurinol on
      concentrations of 6-MMPN and 6-TGN in individuals with a high ratio of these
      metabolites (>20), which is indicative of a poor thiopurine response. METHODS:
      Sixteen individuals were identified who were taking azathioprine or 6-MP, and
      were commenced on allopurinol to improve a high 6-MMPN:TGN ratio. Metabolite
      concentrations were compared before and after commencing allopurinol, and markers
      of disease control were compared. RESULTS: The addition of 100-300 mg allopurinol
      daily and thiopurine dose reduction (17-50% of the original dose) resulted in a
      reduction of the median (and range) 6-MMPN concentration, from 11,643 (3,365
      27,832) to 221 (55-844) pmol/8*10(8) red blood cells (RBC; P=0.0005), increased 6
      TGN from 162 (125-300) to 332 (135-923) pmol/8*10(8) RBC (P=0.0005), and reduced
      the 6-MMPN:6-TGN ratio from 63 (12-199) to 1 (0.1-4.5) (P=0.0005). There was a
      significant reduction in steroid dose requirements at 12 months (P=0.04) and
      trends for improvement in other markers of disease control. One patient developed
      red cell aplasia that resolved upon stopping azathioprine and allopurinol.
      CONCLUSIONS: In those with a high 6-MMPN:6-TGN ratio (>20), response to
      thiopurine treatment might be improved by the addition of allopurinol, together
      with a reduced thiopurine dose and close hematological monitoring.

PMID- 21175794
TI  - Human cytomegalovirus infection inhibits response of chronic hepatitis-C-virus
      infected patients to interferon-based therapy.
AB  - BACKGROUND AND AIM: Cytomegalovirus (CMV) is a ubiquitous pathogen that infects
      the majority of humans. Co-infection of CMV and hepatitis C virus (HCV) may
      deteriorate the prognosis of HCV-infected patients. This study was conducted to
      examine the role of CMV reactivation in determining the response rate to
      treatment with interferon and ribavirin therapy in chronic HCV patients. METHODS:
      Viral loads and genotyping were assessed using reverse transcription polymerase
      chain reaction and Innolipa systems, respectively. Reactivation of CMV in HCV
      patients who were all positive for CMV immunoglobulin G antibodies was tested by
      amplification of the gB1 gene using the end-point dilution quantitative-nested
      polymerase chain reaction method. RESULTS: CMV DNA was detected in 89.7% of non
      responders and in 34.6% of sustained virological responders. Patients with
      reactivated CMV had significantly higher fibrosis scores (72.7%) than those with
      undetectable CMV DNA (23.8%, P=0.002). Patients with positive CMV had higher
      rates of non-response and relapse (79.5%) than those with negative CMV DNA (19%).
      Chronic HCV patients with latent CMV had higher rates of response (81%) to
      treatment than those with reactivated CMV (20.5%, P<0.001). Therefore, HCV
      patients with reactivated CMV and advanced fibrosis were least likely to achieve
      a sustained virological response following interferon therapy. This possibility
      is reduced to 50% of its original value in patients with reactivated CMV without
      fibrosis. CONCLUSIONS: Besides the staging of liver fibrosis, CMV co-infection
      should be considered as an extremely important factor when designing predictive
      models for HCV response to interferon treatment.

PMID- 21175795
TI  - Initial evaluation of the forward-viewing echoendoscope prototype for performing
      fine-needle aspiration, Tru-cut biopsy, and celiac plexus neurolysis.
AB  - BACKGROUND AND AIMS: A forward-viewing echoendoscope (FV-CLA) has been recently
      developed for performing interventional endoscopic ultrasound (EUS). The role of
      FV-CLA in performing standard EUS-guided fine-needle aspiration (FNA), Tru-cut
      biopsy (TCB), and celiac plexus neurolysis (CPN) is unknown. Our aims were to
      evaluate the feasibility of the FV-CLA for performing EUS-guided FNA/TCB and CPN.
      METHODS: In this prospective study conducted over a 3-month period, 30 patients
      were evaluated with the FV-CLA. Procedures performed were FNA in 28 lesions, TCB
      in one, and CPN in five patients. RESULTS: EUS-guided FNA was undertaken at the
      following sites: mediastinum (n=3), liver (n=2), retroperitoneal mass (n=2),
      pancreas head/uncinate (n=9), pancreas body (n=6), pancreas tail (n=4), and
      perigastric lymph node (n=2). The median size of the lesions was 37*34 mm. A
      median of two passes was performed (range: 1-7). Final cytopathology diagnosed
      malignancies in 21 patients, with adenocarcinoma suspected for one.TCB of a
      mediastinal lymph node revealed lymphoma. FNA was benign in six patients. The
      sensitivity, specificity, positive predictive value, and negative predictive
      value for a malignancy diagnosis was 96% (95% confidence interval [CI], 87-96%),
      100% (95% CI, 70-100%), 100% (92-100), and 86% (60-86%), respectively. CPN was
      successful in all five patients. It was easier to deploy the needle from the
      echoendoscope at all locations, including the duodenum, and irrespective of the
      site of the lesion. CONCLUSIONS: The initial evaluation and safety profile of the
      FV-CLA echoendoscope for performing standard FNA/TCB and CPN appear to be
      favorable. The narrow image does not preclude basic therapeutic maneuvers. A
      major advantage appears to be easy needle deployment at any site within reach of
      the echoendoscope.

PMID- 21175796
TI  - Usefulness of endoscopic ultrasound for the prediction of intraoperative bleeding
      of endoscopic submucosal dissection for gastric neoplasms.
AB  - BACKGROUND AND AIM: Intraoperative bleeding is an important determining factor
      for the technical difficulty and safety of endoscopic submucosal dissection (ESD)
      for gastric neoplasms, which was previously difficult to predict before ESD. In
      the present study, we investigated whether endoscopic ultrasound (EUS) could be
      used to preoperatively predict intraoperative bleeding. METHODS: The study
      included 106 patients who underwent EUS before ESD. EUS was used to evaluate the
      submucosal vascular structure. Patients who had at least 10 vascular structures
      per field of view or a vessel at least 500 um in diameter were classified into
      the rich group (Group R), and others were classified into the non-rich group
      (Group N). The two groups were compared retrospectively with respect to procedure
      time, degree of anemia, frequency of clip use, and others. RESULTS: There were 24
      patients in Group R and 82 patients in Group N. Submucosal caner was found in
      54.2% of patients in Group R and 18.3% in Group N. The reduction in hemoglobin
      was 5.8% in Group R and 3.45% in Group N. The procedure time was 151 min in Group
      R and 100 min in Group N. The frequency of clip use was 79.2% in Group R and
      31.7% in Group N. A multivariate analysis revealed a significant difference in
      the depth of invasion and frequency of clip use between the two groups.
      CONCLUSIONS: The results suggest that identification of submucosal vascular
      structure by EUS might allow prediction of intraoperative bleeding during ESD.

PMID- 21175797
TI  - Gastric metaplasia of the duodenum: in vivo diagnosis by endomicroscopy and its
      relationship with functional dyspepsia.
AB  - BACKGROUND AND AIM: Gastric metaplasia (GM) of the duodenum is difficult to
      assess because of its patchy distribution, and the role of GM in functional
      dyspepsia (FD) is not clear. The aims of this study were to determine if
      endomicroscopy could identify GM of the duodenum and whether GM has associations
      with FD. METHODS: A series of 51 patients with FD and 25 asymptomatic controls
      were enrolled. Confocal laser endomicroscopy was performed to evaluate villi
      changes in vivo. Targeted biopsy specimens were then compared with
      histopathological results. RESULTS: The accuracy of the endomicroscopy diagnosis
      of GM during endoscopy was 92.8%, and the sensitivity, specificity, and positive
      and negative predictive values were 86.2%, 97.4%, 89.3%, and 96.6%, respectively.
      The mean kappa-value for interobserver agreement was 0.89. GM in the duodenal
      bulb was more frequent in patients with FD than in the controls (33.3% vs 12%,
      P<0.05), especially in patients with epigastric pain syndrome (47.6% vs 12%,
      P<0.01). CONCLUSIONS: Endomicroscopy is useful for identifying GM, and GM might
      be related to FD. These findings could have potential applicability for duodenal
      screening, and suggest a possible targeting therapy in FD.

PMID- 21175798
TI  - Epidemiological features of infantile hypertrophic pyloric stenosis in Taiwan: a
      national study 1996-2004.
AB  - BACKGROUND AND AIM: The incidence of infantile hypertrophic pyloric stenosis
      (IHPS) varies among different countries and is supposed to be lower in Asian
      countries than in Western countries. However, the incidence of IHPS in Taiwan has
      not been well investigated. METHODS: The National Health Insurance (NHI) program
      was implemented in Taiwan in 1995 and covers most of the population (>99%). We
      used the NHI database to investigate the epidemiological features of IHPS in
      Taiwan and to compare the data with that of other countries. RESULTS: We
      identified 962 new IHPS cases during the period from 1996 to 2004. The overall
      incidence of IHPS was 0.39 (0.34-0.50) cases per 1000 live births. The estimation
      was 0.39-0.59 per 1000 live births after adjustment for the misdiagnosis rate.
      The peak incidence (0.58 per 1000 live births) occurred in winter in 1999. Rates
      were consistently higher in male subjects. The 1-year survival rate was not
      significantly different in the patients receiving pyloromyotomy in medical
      centers, regional hospitals, and district hospitals (P=0.389). CONCLUSIONS:
      Taiwan had the second lowest incidence of IHPS reported in the medical
      literature. IHPS patients can be successfully treated in district and general
      hospitals with good prognosis.

PMID- 21175799
TI  - Correlation of serum pepsinogens and gastrin-17 with atrophic gastritis in
      gastroesophageal reflux patients: a matched-pairs study.
AB  - BACKGROUND AND AIM: An algorithm (GastroPanel) for the non-invasive diagnosis of
      atrophic gastritis has been previously proposed, based on serum pepsinogen-I,
      gastrin-17, and Helicobacter pylori (H. pylori) antibodies. The aim of the
      present study was to evaluate whether serum markers correlate with and predict
      gastric atrophy in gastroesophageal reflux disease (GERD) patients. METHODS: The
      baseline data of the prospective ProGERD study, a study on the long-term course
      of GERD (n=6215 patients), served to select patients with atrophic gastritis
      diagnosed in biopsies from gastric antrum and corpus, and control cases without
      atrophy. A total of 208 pairs were matched for age, sex, GERD status (erosive vs
      non-erosive), presence of Barrett's esophagus, and histological H. pylori status
      were retrieved. Serum pepsinogen-I, gastrin-17, and H. pylori antibodies were
      determined using specific enzyme immunoassays. RESULTS: A significant negative
      correlation was found between the degree of corpus atrophy and the level of serum
      pepsinogen-I. A previously-reported negative correlation between the degree of
      antral atrophy and serum gastrin-17 could not be confirmed. The low sensitivity
      (0.32) and specificity (0.70) of the GastroPanel algorithm were mainly due to
      over diagnosis and under diagnosis of advanced atrophy in the antrum. CONCLUSION:
      The diagnostic validity of the GastroPanel algorithm to diagnose gastric atrophy
      non-invasively is not sufficient for general use in GERD patients.

PMID- 21175800
TI  - Expression and prognostic significance of gastric-specific annexin A10 in diffuse
      and intestinal-type gastric carcinoma.
AB  - BACKGROUND AND AIMS: Annexin A10 (ANXA10) and its liver-specific short isoform
      (ANXA10S) had tissue-restricted expression. The downregulation of ANXA10S is
      correlated with tumor progression and poor prognosis in hepatocellular carcinoma.
      The aim of the present study was to validate the tissue distribution and explore
      the role of the ANXA10 protein expression in gastric carcinoma. METHODS: We
      examined the ANXA10 protein expression in human and animal tissues and 356
      resected primary gastric carcinomas, using specific mouse and rabbit polyclonal
      antibodies, by immunohistochemical staining. RESULTS: The ANXA10 protein is a
      nuclear protein specifically expressed in fetal and adult gastric mucosa and
      Brunner's gland across species, including humans, minipigs, woodchucks, and mice,
      and is commonly lost in gastric mucosa with intestinal metaplasia. The ANXA10
      protein was expressed in 43.5% (155 cases) of gastric carcinomas; 74.2% (98/132)
      in the diffuse-type gastric carcinoma (DGC), 73.7% (28/38) in the mixed-type
      gastric carcinoma, and significantly lower in the intestinal-type gastric
      carcinoma (IGC) and indeterminate groups, 16.8% (28/167) and 5.3% (1/19),
      respectively (P<1*10(-8)). IGC with ANXA10 expression was correlated with a
      higher stage (P=0.049), particularly higher in stage IIIA/IIIB/IV IGC than lower
      stage (IA/IB/II) tumors (P=0.005), but was not correlated with age, sex, and
      nodal status. In contrast, DGC with ANXA10 expression was associated with younger
      age, female patients, and importantly, lower tumor stage and lymph node
      metastasis (P=0.007, P=0.065, P=0.024, and P=0.0014, respectively). Moreover, DGC
      with ANXA10 expression had a better 5-year patient survival (P=0.0048), whereas
      IGC with ANXA10 expression had a lower 5-year survival (P=0.034). CONCLUSIONS:
      The ANXA10 protein expression is a novel marker of gastric differentiation, and
      is differentially expressed in IGC and DGC, with opposite prognostic
      significance.

PMID- 21175801
TI  - Usefulness of catheterless radiotelemetry pH monitoring system to examine the
      relationship between duodenal acidity and upper gastrointestinal symptoms.
AB  - BACKGROUND AND AIM: To clarify the usefulness of a newly designed method for
      measuring intraduodenal pH to examine the relationship between duodenal acidity
      and upper gastrointestinal symptoms during intragastric acid infusion. METHODS:
      The study subjects were six healthy volunteers. A Bravo pH capsule with thread
      fixed to the gastric wall was endoscopically introduced into the second portion
      of the duodenum, and intraduodenal acidity was measured during intragastric
      infusion of 300 mL of 0.1 mol/L hydrochloric acid or pure water through an
      elemental diet tube. The severity of several upper gastrointestinal symptoms were
      assessed by using a 10-cm visual analogue scale every 2 min for up to 30 min, and
      the area under the severity scale-time curve (cm*min.) were calculated. RESULTS:
      The percentage time during 30 min when the intraduodenal pH was <4.0 and was
      significantly greater than during water infusion (61.4+/-6.1% vs 24.8+/-6.5%).
      Several upper gastrointestinal symptoms were observed during acid infusion (acid
      vs water epigastric heaviness, 29.1+/-12.0 vs 2.7+/-1.4; dull epigastric pain,
      8.8+/-4.9 vs 0.7+/-0.7 cm*min/30 min). Intraduodenal pH below 4.0 was correlated
      with the severity of dull pain in the stomach (R(2)=0.342, P=0.044). CONCLUSION:
      The newly designed intraduodenal pH monitoring by using catheterless
      radiotelemetry system is useful to examine the relationship between duodenal
      acidity and upper gastrointestinal symptoms.

PMID- 21175802
TI  - Electron microscopic study of intercellular space: correlation analysis of
      bronchial asthma and gastroesophageal reflux disease.
AB  - BACKGROUND AND AIMS: Bronchial asthma (BA) is considered an extra-esophageal
      syndrome of gastroesophageal reflux disease (GERD) with poor pathophysiological
      background. We analyzed the correlation between GERD and BA, examining esophageal
      epithelium with transmission electron microscopy (TEM), along with clinical
      findings. METHODS: BA patients of controlled and partly-controlled levels were
      enrolled in the study. A pulmonary and gastrointestinal (GI) questionnaire was
      given. Patients with no symptoms joined the control group. Esophageal mucosal
      tissue was taken by esophagogastroduodenoscopy from both groups and processed for
      TEM. Intercellular space (IS) was measured with an image analyzing program, 100
      times for each patient. RESULTS: The control (n=20) and BA (n=20) groups revealed
      no significant differences in baseline characteristics. All BA patients were
      using corticosteroid inhalers, with seven patients having a recent history of
      acute exacerbation. Patients with at least one GI symptom made up 70% (14/20) of
      the BA group, and heartburn and/or regurgitation were detected in 40% of
      patients. Endoscopic findings of GERD were mucosal breaks (n=3). The IS of the
      control group was 0.389+/-0.297 um, while the BA group was 0.806+/-0.556 um
      (P=0.001). The presence of GERD symptoms (P=0.306) and a history of recent asthma
      attacks (P=0.710) did not show significant differences. CONCLUSIONS: The BA group
      showed a significant difference in the dilatation of IS compared to the control
      group, suggesting a higher prevalence of GERD in BA patients and a close
      pathophysiological correlation.

PMID- 21175803
TI  - Aberrant expression and localization of hnRNP-A2/B1 is a common event in human
      gastric adenocarcinoma.
AB  - BACKGROUND AND AIM: Nuclear-matrix proteins can be proteomic markers for cancer
      lesions. The present study aimed to determine the roles of heterogeneous nuclear
      ribonucleoproteins--A2 and B1 (hnRNP-A2/B1) in human gastric carcinogenesis.
      METHODS: Human gastric cancer and non-cancerous tissues were collected for
      immunohistochemical analysis. Proteomics technique, Western blot, laser confocal
      microscope, and real-time quantitative reverse transcription-polymerase chain
      reaction were performed to determine the aberrant expression of nuclear-matrix
      proteins. RESULTS: hnRNP-A2/B1 existed in the nuclear matrix of gastric cancer
      cells, and its expression was enhanced in human gastric cancer and decreased by
      hexamethylene bisacetamide. The colocalization of hnRNP-A2/B1 with c-myc, c-fos,
      p53, and Rb was translocated from the nucleolus to the cytoplasm during the
      differentiation of tumor cells. CONCLUSIONS: hnRNP-A2/B1 affected tumor cell
      differentiation through interaction with oncogenes and tumor-suppressor genes,
      and it was overexpressed in human gastric cancer. We postulate that hnRNP-A2/B1
      could serve as a biomarker for the diagnosis of human gastric cancer.

PMID- 21175804
TI  - Serum levels of platelet-derived growth factor-BB and vascular endothelial growth
      factor as prognostic factors for patients with fulminant hepatic failure.
AB  - BACKGROUND AND AIMS: In animal models for acute liver injury, the administration
      of some angiogenic factors such as vascular endothelial growth factor (VEGF) and
      granulocyte-colony stimulating factor (G-CSF) are shown to reduce liver injury
      and improve liver proliferative capacity. The aim of the present study was to
      assess the role of angiogenic factors in fulminant hepatic failure (FHF).
      METHODS: Serum levels of nine angiogenic factors (angiopoietin-2, follistatin, G
      CSF, hepatocyte growth factor [HGF], interleukin-8, leptin, platelet-derived
      growth factor [PDGF]-BB, platelet endothelial cell adhesion molecule-1 and VEGF)
      were measured using the Bio-Plex Protein Array System in 30 patients, 17 of whom
      were diagnosed with FHF, 13 with acute hepatitis (AH), and 20 controls. RESULTS:
      Serum levels of PDGF-BB and VEGF were lower in FHF patients than AH patients and
      controls (PDGF-BB; 2050+/-1572 pg/mL vs 4521+/-2419 pg/mL vs 8506+/-5500 pg/mL,
      VEGF; 39+/-38 pg/mL vs 144+/-122 pg/mL vs 205+/-121 pg/mL). By using univariate
      logistic regression models, serum levels of PDGF-BB and VEGF were associated with
      poor outcomes. Serum PDGF-BB levels were strongly correlated with serum VEGF
      levels (r=0.70). Furthermore, serum PDGF-BB levels were significantly correlated
      with platelet counts (r=0.79), PT activity (r=0.37) and D.Bil/T.Bil ratio
      (r=0.50), while serum VEGF levels were significantly correlated with platelet
      counts (r=0.68) and PT activity (r=0.38). CONCLUSIONS: We consider that serum
      levels of PDGF-BB and VEGF are worth investigating as biomarkers for predicting
      outcomes of FHF patients.

PMID- 21175806
TI  - Community-based screening for hepatocellular carcinoma in elderly residents in a
      hepatitis B- and C-endemic area.
AB  - BACKGROUND AND AIM: The aim of the present study was to elucidate a reasonable
      model and the efficacy of hepatocellular carcinoma (HCC) screening on an elderly
      population. METHODS: Two-stage HCC screening was conducted in a hepatitis C virus
      (HCV)-endemic area. First, participants underwent blood tests for hepatitis B
      surface antigen (HBsAg), anti-HCV antibody, serum alpha-fetoprotein (AFP),
      aspartate aminotransferase, alanine aminotransferase, and platelet count.
      Patients who were abnormal for any of the six markers were enrolled for second
      stage ultrasonography. Suspected cases were referred for confirmation. HCC cases
      were followed for 4 years. All patients were linked to national mortality and
      cancer register databases to identify newly-developed HCC, 30 months after
      screening. RESULTS: A total of 461 males and 541 females were screened for HCC,
      with 15.1% testing positive for HBsAg and 44.3% positive for anti-HCV. Among
      them, 619 (61.8%) met the criteria of ultrasonographic screening; 527 (85.1%)
      responded, and 16 confirmed HCC (male/female = 8/8, 68.8+/-8 years) cases were
      detected. All tumor diameters were less than 5 cm, and six were less than 2 cm.
      AFP and thrombocytopenia were two independent predictive factors of HCC. The
      overall survival rates of detected cases were 93.8% and 56.3% was 1 and 4 years,
      respectively. The only good prognostic predictor was "underwent curative
      treatment". Another seven non-HCC residents developed HCC after screening, and
      five of these were with either thrombocytopenia or AFP elevation. CONCLUSION:
      Under economical consideration, AFP and platelet count should be feasible
      screening markers of risk identification. Early detection and prompt treatment
      results in good prognosis in an aged population.

PMID- 21175805
TI  - Long-term follow-up of patients with hepatitis B e antigen negative chronic
      hepatitis B.
AB  - BACKGROUND AND AIM: After hepatitis B virus (HBV) e antigen (HBeAg)
      seroconversion, HBV-DNA continues to replicate, and HBeAg-negative patients still
      face the risk of liver disease progression. We investigated the predictive
      factors for alanine aminotransferase (ALT) elevation, antiviral drug use, and
      hepatocellular carcinoma (HCC) occurrence in HBeAg-negative patients. METHODS:
      Age, sex, ALT, platelet counts, HBV-DNA levels, genotype, antidiabetic drug use,
      body mass index, smoking, and alcohol consumption were analyzed for a total of
      244 HBV carriers who were HBeAg-negative. RESULTS: Of 244 HBeAg-negative
      patients, 158 (64.8%) showed normal ALT levels at baseline. Multivariate Cox
      hazard regression analysis identified high HBV-DNA levels and high ALT at
      baseline as independent risk factors for ALT elevation in the patients with
      normal ALT at baseline. The threshold ALT and HBV-DNA levels were determined to
      be 31 IU/L and 5.3 log copies/mL, respectively. Seventeen (7.0%) patients used
      antiviral drugs. Multivariate Cox hazard regression analysis identified high HBV
      DNA levels (threshold, 5.7 log copies/mL), the use of antidiabetic drugs, and
      daily alcohol consumption at baseline as an independent risk factor for the use
      of antiviral drugs in HBeAg-negative patients. In 10 patients (4.1%), HCC was
      detected, and a low platelet count (threshold, 10.0*10(4)/mm(3)) was associated
      with the occurrence of HCC. CONCLUSION: This study identified predictors of
      future active liver disease in HBeAg-negative patients, i.e. ALT elevation,
      unavoidable use of antiviral drugs, and occurrence of HCC.

PMID- 21175807
TI  - Hepatocellular carcinoma with persistent hepatitis B virus infection shows
      unusual downregulation of Ras expression and differential response to Ras
      mediated signaling.
AB  - BACKGROUND AND AIM: Persistent infection with hepatitis B virus (HBV) is a major
      etiological risk factor for hepatocellular carcinoma (HCC). The host cellular
      components involved in the progression of the carcinoma are still unclear. In the
      present study we aimed to evaluate Ras mediated signaling in hepatocellular
      carcinoma with persistent HBV infection. METHODS: To gain insight into the role
      of Ras mediated signaling in HBV mediated carcinogenesis we evaluated Ras
      functionality by mutation analysis, reverse transcription-polymerase chain
      reaction, immunohistochemistry (IHC), Ras-guanosine triphosphate bound
      functionality assay and Ras-mediated downstream signaling in a cohort of primary
      HCC tissues positive for HBV-DNA. RESULTS: Mutation in codon 12 of K-ras appeared
      to be an uncommon event in the pathogenesis of HCC. We found unusually low levels
      of Ras expression in HCC compared with those with normal liver and chronic liver
      disease (cirrhosis and chronic hepatitis). Considerable heterogeneity was found
      with respect to Ras-mediated signaling events (pRaf, pMAPK and pAKT). The
      hepatoma cell line (Hep3B) with integrated HBV showed upregulation in expression
      and activation of Ras and its downstream signaling in comparison to HBV a
      negative cell line (HepG2). The contrasting result between the cell lines and
      primary tumors is worthy of note. CONCLUSIONS: The unusual finding on
      downregulation of Ras expression in primary HCC tumors in the present study
      together with tumor heterogeneity with respect to Ras-mediated signaling events
      prompts a new role of the wild type K-Ras as a possible growth suppressor and a
      stochastic model for progression of hepatic cancer.

PMID- 21175809
TI  - Acute allograft rejection in human liver transplant recipients is associated with
      signaling through toll-like receptor 4.
AB  - BACKGROUND AND AIMS: Toll-like receptor (TLR) signaling is a crucial step in
      initiating adaptive immune responses. In addition to recognizing endotoxin, TLR4
      also recognizes endogenous ligands ('damage-associated structures'), which are
      released into the circulation in the peri-transplantation period. TLR2 to a
      lesser extent also recognizes these endogenous ligands. Multiple studies
      involving solid organ transplants demonstrate a clear association between TLR4
      and allograft rejection. In the present study we assessed whether an association
      exists between TLR4 and TLR2-dependent responses and acute liver allograft
      rejection. METHODS: The sample included 26 liver transplant recipients. Blood was
      taken pre-transplant and at multiple points over the first 14 days post
      transplant. Monocytes were stimulated with TLR4 and TLR2 ligands,
      lipopolysaccharide and Pam-3-Cys, respectively. Monocyte TLR expression was
      determined using flow cytometry; enzyme-linked immunosorbent assays measured
      tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) production.
      RESULTS: Nine (34.6%) patients experienced rejection. No differences existed in
      age, sex, disease or immunosuppression between rejectors and non-rejectors.
      Baseline TLR4 expression was significantly higher in rejectors (1.36 vs 1.02,
      P=0.01). There was no difference in TLR2 expression. In rejectors, baseline TLR4-
      and TLR2-dependent production of TNF-alpha and IL-6 was also significantly
      increased. Post-transplant, the two groups differed with regard to TLR4-dependent
      TNF-alpha production, with rejectors demonstrating progressive downregulation
      over the first week. CONCLUSIONS: Prior to liver transplantation, patients who
      subsequently experience rejection demonstrate robust TLR4-dependent immune
      responses, which are not seen in those who do not reject. This supports the
      theory that damage-associated structures signaling through TLR4 may be
      responsible for the early activation of alloimmune T-cells, favoring allograft
      rejection.

PMID- 21175808
TI  - Clinical outcome of 251 patients with extrahepatic metastasis at initial
      diagnosis of hepatocellular carcinoma: does transarterial chemoembolization
      improve survival in these patients?
AB  - BACKGROUND AND AIMS: The therapeutic efficacy of transarterial chemoembolization
      (TACE) has not been evaluated in hepatocellular carcinoma (HCC) patients with
      extrahepatic metastasis. We investigated the efficacy of TACE with/without
      systemic chemotherapy (s-chemo) in these patients. METHODS: We performed a
      survival analysis of consecutive HCC patients with extrahepatic metastasis,
      diagnosed at initial presentation according to treatment modality after
      stratification, using the Child-Pugh classification and intrahepatic HCC T stage,
      retrospectively. RESULTS: Between 2005 and 2007, 251 patients were newly
      diagnosed with HCC involving extrahepatic metastasis at our institution. Among
      those, 226 were classified as Child-Pugh A-B and the other 25, Child-Pugh C.
      Within the Child-Pugh A-B group, repeated TACE or transarterial chemoinfusion
      (TACI) was performed with/without s-chemo in 171 patients. Eight of 226 received
      s-chemo alone, and 47, conservative management (CM) alone. The median survival
      time of patients treated with TACE/TACI with s-chemo, TACE/TACI alone, and CM was
      10, 5, and 2.9 months in patients classified as Child-Pugh A and T3-stage HCC
      (TACE/TACI with s-chemo vs CM, P=0.0354; TACE/TACI alone vs CM, P=0.0553) and
      7.1, 2.6, and 1.6 months in Child-Pugh B and T3-stage patients, respectively
      (TACE/TACI with s-chemo vs CM, P=0.0097; TACE/TACI alone vs CM, P<0.0001).
      Individual treatment with TACE/TACI or sorafenib showed independent prognostic
      significance in the multivariate analysis. CONCLUSION: Repeated TACE could show
      significant survival benefits in metastatic HCC patients with conserved liver
      function and intrahepatic HCC T3 stage. The survival data of our study could be
      used as a historical control for TACE monotherapy in future clinical trials
      evaluating combination treatments containing TACE in these patients.

PMID- 21175810
TI  - Spleen stiffness measurement using Fibroscan for the noninvasive assessment of
      esophageal varices in liver cirrhosis patients.
AB  - BACKGROUND AND AIM: Splenomegaly in a common finding in liver cirrhosis that
      should determine changes in the spleen's density because of portal and splenic
      congestion and/or because of tissue hyperplasia and fibrosis. These changes might
      be quantified by elastography, so the aim of the study was to investigate whether
      spleen stiffness measured by transient elastography varies as liver disease
      progresses and whether this would be a suitable method for the noninvasive
      evaluation of the presence of esophageal varices. PATIENTS AND METHODS: One
      hundred and ninety-one patients (135 liver cirrhosis, 39 chronic hepatitis and 17
      healthy controls) were evaluated by transient elastography for measurements of
      spleen and liver stiffness. Cirrhotic patients also underwent upper endoscopy for
      the diagnosis of esophageal varices. RESULTS: Spleen stiffness showed higher
      values in liver cirrhosis patients as compared with chronic hepatitis and with
      controls: 60.96 vs 34.49 vs 22.01 KPa (P<0.0001). In the case of liver cirrhosis,
      spleen stiffness was significantly higher in patients with varices as compared
      with those without (63.69 vs 47.78 KPa, P<0.0001), 52.5 KPa being the best cut
      off value, with an area under the receiver operating characteristic of 0.74.
      Using both liver and spleen stiffness measurement we correctly predicted the
      presence of esophageal varices with 89.95% diagnostic accuracy. CONCLUSION:
      Spleen stiffness can be assessed using transient elastography, its value
      increasing as the liver disease progresses. In liver cirrhosis patients spleen
      stiffness can predict the presence, but not the grade of esophageal varices.
      Esophageal varices' presence can be better predicted if both spleen and liver
      stiffness measurements are used.

PMID- 21175811
TI  - The usefulness of liver stiffness measurement using FibroScan in chronic
      hepatitis C in South Korea: a multicenter, prospective study.
AB  - AIM: We investigated the accuracy of liver stiffness measurement (LSM) in chronic
      hepatitis C (CHC) in a multicenter, prospective study in South Korea. METHODS:
      Between June 2005 and July 2009, 91 CHC patients without a previous history of
      antiviral treatment, clinical evidences of cirrhosis, coinfection with other
      viruses, and heavy alcohol consumption and with alanine aminotransferase (ALT)
      <=5x upper limit of normal, total bilirubin <=1.5 mg/dL, sufficient liver biopsy
      quality (>=15 mm and more than six portal tracts), interquartile range to median
      liver stiffness (LS) value ratio <=0.21, and more than 10 valid measurements,
      were recruited. The Batts and Ludwig scoring system was used for histologic
      assessment. Age-platelet index (API), aspartate aminotransferase (AST)-to
      platelet ratio index (APRI), and age-spleen-platelet ratio index (ASPRI) were
      calculated. Area under the receiver operating characteristic curve (AUROC) was
      used to evaluate the performance of LSM and other noninvasive models. RESULTS:
      The mean age was 47.9 years, and the mean LS value was 7.7 kPa (44 men and 47
      women). LS value was highly correlated to the fibrosis stages (r=0.835, P<0.001).
      The AUROCs of LSM were 0.909 for >=F2, 0.993 for >=F3, and 0.970 for F=4 and were
      superior to those of API (0.72, 0.858, and 0.948, respectively), APRI (0.780,
      0.887, and 0.904, respectively), and ASPRI (0.713, 0.862, and 0.957,
      respectively). The optimal cutoff LS values were 6.2 kPa for >=F2, 7.7 kPa for
      >=F3, and 11.0 kPa for F=4. CONCLUSIONS: Our data suggest that LSM can accurately
      assess liver fibrosis in patients with CHC and be applied in South Korea.

PMID- 21175812
TI  - Berberine inhibits angiogenic potential of Hep G2 cell line through VEGF down
      regulation in vitro.
AB  - BACKGROUND AND AIM: Berberine, an herbal alkaloid, has been reported to have
      promotion potential of apoptosis and anticancer effect on a variety of human
      tumor cells. To obtain more specific understanding of those consequences of
      berberine on hepatocellular carcinoma (HCC) and the tumor microenvironment, we
      conducted in vitro experiments to investigate the inhibitory effect of berberine
      on tumor-induced angiogenesis using HCC cells and human umbilical vein
      endothelial cells (HUVECs). METHODS: Human umbilical vein endothelial cell growth
      was quantified with the CCK-8 cell proliferation assay; cell migration was
      observed with a Boyden chamber (Transwell, Corning, Lowell, MA, USA), and
      angiogenesis was assessed by endothelial tube formation in Matrigel in vitro. In
      addition, VEGF level was determined by ELISA and VEGF mRNA expression by RT-PCR.
      RESULTS: Berberine inhibited the capacity of HCC to stimulate HUVEC's
      proliferation, migration and endothelial tube formation, suggesting that
      berberine could influence the cross-talk between the HCC cell and vascular
      endothelial cells. These results demonstrate berberine's antiangiogenesis
      property and its clinical potential as an inhibitor of tumor angiogenesis.
      Subsequently analyses reveal that berberine prevents secretion of VEGF from HCC
      and down-regulates VEGF mRNA expression. CONCLUSION: These findings strongly
      suggest that berberine is a potential antiangiogenic agent and a promising
      antitumor drug for HCC.

PMID- 21175813
TI  - microRNA expression alteration after arsenic trioxide treatment in HepG-2 cells.
AB  - BACKGROUND AND AIM: More and more microRNA (miRNA) are found to be involved in
      tumor genesis and progress. Arsenic trioxide has been an effective
      chemotherapeutic drug in cancer therapy for many years. In this study, we aimed
      to find the miRNA involved in the mechanisms of arsenic trioxide treatment in
      cancer therapy. METHODS: We detected the expression profile of miRNA by miRNA
      microarray and quantitative real-time polymerase chain reaction. Cell viability
      assay, flow cytometry analysis, prediction of miRNA targets, Western blot
      analysis and luciferase reporter assay were carried out to determine the role of
      one selected miRNA, namely mir-29a, in affecting the biological behaviors of HepG
      2 cells. RESULTS: Among the 677 human miRNA in the microarray, five miRNA were
      upregulated and four were downregulated in HepG-2 cells treated with arsenic
      trioxide compared to their controls. If only changes above two folds were
      considered, four miRNA were identified, namely miR-24, miR-29a, miR-30a and miR
      210, which were all upregulated. Among them, miR-29a showed a positive
      therapeutic effect in liver cancer cells by inhibiting cell growth and inducing
      cell apoptosis, and PPM1D was confirmed to be the target gene of miR-29a.
      Furthermore, a synergy effect was detected between miR-29a and arsenic trioxide.
      CONCLUSIONS: Arsenic trioxide altered miRNA expression profile in HepG-2 cells.
      Among the altered miRNA, miR-29a seemed to take a role in the mechanism of
      arsenic trioxide in liver cancer therapy. The synergy effect between miR-29a and
      arsenic trioxide may offer this drug a new chance in cancer therapy by decreasing
      its dose and toxic side-effects.

PMID- 21175814
TI  - Glycine maintains mitochondrial activity and bile composition following warm
      liver ischemia-reperfusion injury.
AB  - BACKGROUND AND AIM: Experimental studies have shown protective effect by the non
      essential amino acid glycine to liver ischemia-reperfusion (I/R) injury but the
      mechanism of action is unknown. METHODS: A rabbit model of hepatic lobar I/R was
      used. Three groups of animals (n=6) were studied: Sham group (laparotomy alone),
      ischemia reperfusion (I/R) group (1 h of liver lobar ischemia and 6 h of
      reperfusion), and a glycine I/R group (intravenous glycine 5 mg/kg prior to the
      I/R protocol). Systemic and hepatic hemodynamics, degree of liver injury (bile
      flow, transaminases), hepatic microcirculation, mitochondrial activity (redox
      state of cytochrome oxidase), bile composition and cytokines (tumor necrosis
      factor-alpha and interleukin-8) were measured during the experiment. RESULTS:
      Glycine administration increased portal blood flow, bile production, hepatic
      microcirculation and maintained cytochrome oxidase activity as compared with the
      I/R group during reperfusion. Glycine also reduced bile lactate surge and
      stimulated acetoacetate release in bile during reperfusion versus the I/R group.
      Cytokine levels (tumor necrosis factor-alpha, interleukin-8) and hepatocellular
      injury (aspartate aminotransferase and alanine aminotransferase) were
      significantly reduced by glycine administration. CONCLUSION: Intravenous glycine
      administration reduces liver warm I/R injury by reducing the systemic
      inflammatory response, and maintaining cellular energy production.

PMID- 21175815
TI  - Epimorphin protects hepatocytes from oxidative stress by inhibiting mitochondrial
      injury.
AB  - BACKGROUND AND AIMS: Many investigations have demonstrated that cell injuries
      caused by generation of reactive oxygen species (ROS) is a common mechanism of
      various hepatic disorders. Recently, we have demonstrated that epimorphin,
      originally cloned as a mesenchymal protein, protects cultured intestinal
      epithelial cells from ROS. We therefore examine whether epimorphin protects
      primary cultured hepatocytes from ROS-induced cell injury. METHODS: We explored
      the cell viability and the intracellular ROS levels of purified murine
      hepatocytes after exposure to 0.5 mM H(2)O(2) with or without pretreatment of
      epimorphin. Then, we observed mitochondrial permeability transition (MPT) and
      depolarization using confocal microscopy to make clear the mechanism that
      epimorphin inhibited cell injuries after exposure to H(2)O(2). In addition, to
      clarify the signaling pathways related to cell survival, we carried out Western
      blotting analysis with phosphorylated stress-activated protein kinase/c-Jun N
      terminal kinase (SAPK/JNK) polyclonal antibody to evaluate the inhibition of JNK
      by epimorphin. Finally, we evaluated the cell viability in hepatocytes
      administered JNK inhibitor. RESULTS: Epimorphin protected primary cultured
      hepatocytes from H(2)O(2)-induced cell injuries independent of intracellular ROS
      levels. Epimorphin also inhibited onset of MPT, depolarization of the
      mitochondrial membrane potential, and eventually cell killing. The cell
      protective function of epimorphin after exposure to H(2)O(2) was not dependent on
      Akt signaling but on JNK signaling. CONCLUSION: Epimorphin can protect
      hepatocytes from MPT-dependent cell injury induced by ROS. Since hepatic
      disorders could be caused by MPT-dependent cell injuries with excessive ROS,
      epimorphin might open a new therapeutic avenue for hepatic disorders.

PMID- 21175816
TI  - Education and imaging. Gastrointestinal: "Walk in the snow": Boerhaave syndrome.

PMID- 21175817
TI  - Education and imaging. Gastrointestinal: Sigmoidocecal fistula diagnosed with
      colonoscopy.

PMID- 21175818
TI  - Education and imaging. Gastrointestinal: Successful obliteration of bleeding
      duodenal varices using band ligation.

PMID- 21175819
TI  - Education and imaging. Hepatobiliary and pancreatic: Primary hepatic lymphoma.

PMID- 21175820
TI  - Education and imaging. Hepatobiliary and pancreatic: Multinodular fatty liver
      associated with porphyria cutanea tarda.

PMID- 21175821
TI  - A survey of the use of grading scales for contact lens complications in
      optometric practice.
AB  - PURPOSE: The aim of this study was to investigate the extent and pattern of use
      of grading scales for contact lens complications ('grading scales') in optometric
      practice. METHODS: An anonymous postal survey was sent to all 756 members of the
      Queensland Division of Optometrists Association Australia. Information was
      elicited relating to level of experience, practice type and location, and mode of
      usage of grading scales. RESULTS: Survey forms were returned by 237 optometrists,
      representing a 31 per cent response rate. The majority of respondents (61 per
      cent) reported using grading scales frequently in practice, while 65 per cent of
      these preferred to use the Efron Grading Scales for Contact Lens Complications.
      Seventy-six per cent of optometrists use a method of incremental grading rather
      than simply grading with whole numbers. Grading scales are more likely to be used
      by optometrists who have recently graduated (p < 0.001), have a postgraduate
      certificate in ocular therapeutics (p = 0.018), see more contact lens patients (p
      = 0.027) and use other forms of grading scales (p < 0.001). The most frequently
      graded ocular conditions were corneal staining, papillary conjunctivitis and
      conjunctival redness. The main reasons for not using grading scales included a
      preference for sketches, photographs or descriptions (87 per cent) and
      unavailability of scales (29 per cent). CONCLUSION: Grading scales for contact
      lens complications are used extensively in optometric practice for a variety of
      purposes. This tool can now be considered as an expected norm in contact lens
      practice. We advocate the incorporation of such grading scales into professional
      guidelines and standards for good optometric clinical practice.

PMID- 21175822
TI  - Drug delivery to the posterior segment of the eye through hydrogel contact
      lenses.
AB  - PURPOSE: Despite pharmacological advances, delivery of drugs to the posterior
      segment of the eye remains problematic. We investigated the ability of hydrogel
      contact lenses to deliver small-molecule steroids, as well as larger biological
      molecules to the posterior segment. METHODS: Release characteristics of steroid
      instilled lenses were studied in vitro. Drug delivery to the posterior segment of
      the eye was evaluated in a rabbit model, in which hydrogel contact lenses treated
      with diluted steroids (prednisolone or beclomethasone) were placed on rabbit
      corneas for four hours on days 1, 2, 5, 8 and 10. The amount of drug in plasma,
      posterior segment tissue and vitreous humour was measured with high-performance
      liquid chromatography-tandem mass spectrometry. In a further preliminary
      investigation, two rabbits were treated with ranibizumab. RESULTS: The lenses
      released prednisolone and beclomethasone in saline over a six-hour period at a
      declining rate. Prednisolone was found in posterior segment tissue from six of
      six rabbits at concentrations ranging from 26.8 to 166 ng/g and in vitreous
      humour from two of six rabbits. Beclomethasone was detected in posterior segment
      tissue from three rabbits but was not found in the vitreous humour. Ranibizumab
      was detected in posterior segment tissue in a range from 0.19 ng/mL to 0.5183
      ng/mL. CONCLUSIONS: Hydrogel contact lenses are a non-invasive, periocular drug
      delivery device capable of achieving measurable drug levels in posterior segment
      tissue.

PMID- 21175823
TI  - Preliminary clinical analysis of neovascular glaucoma secondary to carotid artery
      disease.
AB  - BACKGROUND: Neovascular glaucoma (NVG) is a rare but severe complication of
      hypoperfusion retinopathy. Our objective was to analyse the clinical features of
      NVG secondary to carotid artery atherosclerosis, moyamoya disease and Takayasu
      arteritis. METHODS: Thirty-six cases (36 eyes) with hypoperfusion retinopathy
      associated with NVG were retrospectively analysed. Each patient had their visual
      acuity assessed and fundus examined by fundus fluorescein angiography, colour
      Doppler flow imaging, magnetic resonance angiography, digital subtraction
      angiography and other techniques. RESULTS: Eyes belonging to 30 males and six
      females were analysed. There were 24 right eyes and 12 left eyes. The ages of
      these patients ranged 18 to 78 years and the mean age was 40 years. The visual
      acuities ranged from light perception to 0.8 (decimal notation). Posterior
      segment manifestations included mid-peripheral intraretinal haemorrhages and
      narrowed retinal arteries. All eyes were associated with either an ipsilateral
      common carotid artery obstruction or a severe bilateral obstruction of the
      internal carotid arteries. CONCLUSIONS: The characteristic clinical features are
      presented during the process of the disease. Degeneration of the ocular fundus
      was predominantly on one side. The retinal manifestations included mid-peripheral
      haemorrhages and dilated retinal veins. High intraocular pressure and excavation
      and atrophy of the optic disc were common. In the eyes that were examined,
      neovascularisation was observed in the iris and anterior chamber and various
      visual field defects were present.

PMID- 21175824
TI  - Access to low-vision rehabilitation services: barriers and enablers.
AB  - BACKGROUND: The current mismatch between the need for and uptake of low-vision
      services has been attributed to various barriers including different service
      delivery models and referral pathways. This study evaluates the referral pathway
      and low-vision service provision of the Royal Society for the Blind (RSB) in
      South Australia. METHODS: All new referrals from the 2008-2009 financial year to
      the RSB were reviewed. Initially, patients were contacted by a triage officer
      within one week of referral. Initial appointments were made in the Low Vision
      Clinic with a multidisciplinary team. Reasons for declining the appointment or
      non-attendance were tracked via telephone. RESULTS: There were 1116 patients
      referred over a 12-month period and 1082 (97 per cent) were reviewed in the Low
      Vision Clinic. Most attendees (92 per cent) lived within 50 kilometres of the
      clinic. There were 34 referred patients, who declined or did not attend the
      assessment. All non-attendees also lived within 50 kilometres of the Low Vision
      Centre. Concurrent major health problems (27 per cent) and patients not feeling
      the need for low-vision rehabilitation (27 per cent) were the most common reasons
      for not accessing the service. Only 125 patients (11.6 per cent) accessed
      volunteer transport services and only 24 patients (2.2 per cent) needed an
      interpreter service. CONCLUSION: The attendance rate is significantly higher than
      in other published studies. The distance to travel or transport difficulties were
      not significant barriers. Patient perception that either the service was not
      required or would not help them was the main barrier. The referral and triage
      process appeared to be a major enabler of low-vision service uptake.

PMID- 21175825
TI  - The impact of continuing professional development on ophthalmic dispensing of
      progressive addition lenses in the Asia-Pacific region.
AB  - BACKGROUND: Discrepancies exist in optometric education, practice and regulation
      across the Asia-Pacific region and the competence of optometric practitioners in
      adopting new lens technologies may vary widely. Over the past 10 years, a
      continuing professional development program, Varilux Academy Asia-Pacific (VAAP),
      was implemented and conducted in countries across the Asia-Pacific region to
      improve practitioners' understanding of optometric fitting principles, with
      special emphasis on progressive addition lenses (PAL). The aim was to demonstrate
      the effectiveness of VAAP and to compare the competence of practitioners across
      the Asia-Pacific region in new lens fitting technologies. METHODS: From 2002 to
      2008, all VAAP participants from 12 countries across Asia-Pacific were invited to
      complete a pre- and a post-program competency test and a post-program survey.
      RESULTS: A total of 5658 practitioners were trained, and 69.9 per cent (n =
      3,957) of participants completed the pre- and post-program competency test; 80.9
      per cent (n = 4,580) of participants completed the post-program survey. There was
      a significant improvement in competency after VAAP (mean change = 19.4 per cent
      +/- 3.3, p < 0.01). Before VAAP was conducted the mean competency score was
      significantly lower in developing countries compared with developed countries
      (mean score of developed countries = 50.6 +/- 10.3, mean score of developing
      countries = 45.0 +/- 7.8, p < 0.05). After VAAP, these differences were not
      significant. Confidence in fitting PAL improved by 27.1 per cent. Most
      participants (91.6 per cent) intended to fit more PAL and 96.8 per cent of
      participants rated the program as excellent or good. CONCLUSION: Our findings
      highlight the need for further continuing education of practitioners across the
      Asia-Pacific region. The results of the training course indicate that, across
      Asia-Pacific, continuing education courses in ophthalmic optics and dispensing
      encompassing modern lens design and best practice fitting principles are
      warranted.

PMID- 21175826
TI  - Valuing ecosystem services in terms of ecological risks and returns.
AB  - The economic valuation of ecosystem services is a key policy tool in stemming
      losses of biological diversity. It is proposed that the loss of ecosystem
      function and the biological resources within ecosystems is due in part to the
      failure of markets to recognize the benefits humans derive from ecosystems.
      Placing monetary values on ecosystem services is often suggested as a necessary
      step in correcting such market failures. We consider the effects of valuing
      different types of ecosystem services within an economic framework. We argue that
      provisioning and regulating ecosystem services are generally produced and
      consumed in ways that make them amenable to economic valuation. The values
      associated with cultural ecosystem services lie outside the domain of economic
      valuation, but their worth may be expressed through noneconomic, deliberative
      forms of valuation. We argue that supporting ecosystem services are not of direct
      value and that the losses of such services can be expressed in terms of the
      effects of their loss on the risk to the provision of the directly valued
      ecosystem services they support. We propose a heuristic framework that considers
      the relations between ecological risks and returns in the provision of ecosystem
      services. The proposed ecosystem-service valuation framework, which allows the
      expression of the value of all types of ecosystem services, calls for a shift
      from static, purely monetary valuation toward the consideration of trade-offs
      between the current flow of benefits from ecosystems and the ability of those
      ecosystems to provide future flows.

PMID- 21175827
TI  - Variation in physiological stress between bridge- and cave-roosting Brazilian
      free-tailed bats.
AB  - Since the late 1980s, Brazilian free-tailed bats (Tadarida brasiliensis) have
      increasingly used bridges as roosts in the southern United States. We examined
      differences in blood cortisol levels, body condition, and parasite load, as
      measures of physiological stress in bats roosting in bridges and bats roosting in
      caves. We collected data during three periods, coinciding with female phases of
      reproduction. For all measures, bats were captured during the nightly emergence
      from the roost and immediately sampled. Cortisol levels were significantly higher
      during pregnancy and lactation and in individuals with lower body-condition
      scores (length of forearm to mass ratio) and significantly higher in bats
      roosting in caves than in those roosting in bridges. Thus, we concluded that
      individuals of this species that roost in bridges are not chronically stressed
      and seem to be unaffected by human activities present at bridges. This is a rare
      documented instance where a human-dominated environment does not appear to be
      adversely affecting the physiological health of a free-ranging animal.

PMID- 21175828
TI  - Generation of priority research questions to inform conservation policy and
      management at a national level.
AB  - Integrating knowledge from across the natural and social sciences is necessary to
      effectively address societal tradeoffs between human use of biological diversity
      and its preservation. Collaborative processes can change the ways decision makers
      think about scientific evidence, enhance levels of mutual trust and credibility,
      and advance the conservation policy discourse. Canada has responsibility for a
      large fraction of some major ecosystems, such as boreal forests, Arctic tundra,
      wetlands, and temperate and Arctic oceans. Stressors to biological diversity
      within these ecosystems arise from activities of the country's resource-based
      economy, as well as external drivers of environmental change. Effective
      management is complicated by incongruence between ecological and political
      boundaries and conflicting perspectives on social and economic goals. Many
      knowledge gaps about stressors and their management might be reduced through
      targeted, timely research. We identify 40 questions that, if addressed or
      answered, would advance research that has a high probability of supporting
      development of effective policies and management strategies for species,
      ecosystems, and ecological processes in Canada. A total of 396 candidate
      questions drawn from natural and social science disciplines were contributed by
      individuals with diverse organizational affiliations. These were collaboratively
      winnowed to 40 by our team of collaborators. The questions emphasize
      understanding ecosystems, the effects and mitigation of climate change,
      coordinating governance and management efforts across multiple jurisdictions, and
      examining relations between conservation policy and the social and economic well
      being of Aboriginal peoples. The questions we identified provide potential links
      between evidence from the conservation sciences and formulation of policies for
      conservation and resource management. Our collaborative process of communication
      and engagement between scientists and decision makers for generating and
      prioritizing research questions at a national level could be a model for similar
      efforts beyond Canada.

PMID- 21175829
TI  - Incorporation of spatial and economic analyses of human-use data in the design of
      marine protected areas.
AB  - Social, economic, and ecological criteria contribute to the successful design,
      implementation, and management of marine protected areas (MPAs). In the context
      of California's Marine Life Protection Act Initiative, we developed a set of
      methods for collecting, compiling, and analyzing data about the spatial extent
      and relative economic importance of commercial and recreational fishing. We
      interviewed 174 commercial fishers who represented the major fisheries in the
      initiative's north-central coast region, which extends from Point Arena south to
      Pigeon Point. These fishers provided data that we used to map the extent of each
      of the fishing grounds, to weight the relative importance of areas within the
      grounds, to characterize the operating costs of each fishery, and to analyze the
      potential economic losses associated with proposed marine protected areas. A
      regional stakeholder group used the maps and impact analyses in conjunction with
      other data sets to iteratively identify economic and ecological trade-offs in
      designations of different areas as MPAs at regional, port, and fishery extents.
      Their final proposed MPA network designated 20% of state waters as MPAs.
      Potential net economic loss ranged from 1.7% to 14.2% in the first round of
      network design and totaled 6.3% in the final round of design. This process is a
      case study in the application of spatial analysis to validate and integrate local
      stakeholder knowledge in marine planning.

PMID- 21175830
TI  - Minerals in dialysis therapy: an introduction.
AB  - The 180 l of glomerular filtrate formed each day contain some 1100 g (2.5 pounds)
      of sodium chloride, of which only 5-10 g are excreted in the urine--95% is
      reabsorbed by the tubules. Some 425 g (nearly a pound) of sodium bicarbonate and
      145 g of glucose are filtered, and more than 99% of both are reabsorbed. Also
      filtered, only to be reabsorbed, are substantial quantities of potassium,
      calcium, magnesium, phosphate, sulfate, amino acids, vitamins, and many other
      substances valuable to the body. It is no exaggeration to say that the
      composition of the blood is determined not by what the mouth takes in but by what
      the kidneys keep: they are the master chemists of our internal environment,
      which, so to speak, they manufacture in reverse by working it over completely
      some fifteen times a day...Our bones, muscles, glands, even our brains are called
      upon to do only one kind of physiological work, but our kidneys are called upon
      to perform an innumerable variety of operations. Bones can break, muscles can
      atrophy, glands can loaf, even the brain can go to sleep, without immediately
      endangering our survival; but should the kidneys fail to manufacture the proper
      kind of blood neither bone, muscle, gland nor brain could carry on (1).

PMID- 21175831
TI  - Sodium balance in maintenance hemodialysis.
AB  - Maintenance of extracellular fluid volume balance is an essential role of chronic
      maintenance hemodialysis (HD). In this population, this balance is determined by
      salt intake during the interdialytic period and sodium removal in HD sessions.
      Most of the sodium in a HD session is removed by ultrafiltration of plasma water,
      and the diffusion process becomes responsible for the fine tuning of sodium
      balance. The observation of little variation in pre-HD serum sodium denotes that
      HD patients have an individual, stable osmolar set point. A positive dialysate-to
      plasma sodium gradient is associated with increased thirst, interdialytic weight
      gain, and hypertension. To achieve an isonatric HD session, dialysate sodium
      concentration should approximately match patient's serum sodium, and all sodium
      gained in the interdialytic period must be removed by convection. The pre-HD
      serum sodium concentration may be used as a reference for dialysate sodium
      prescription in chronic HD. In this article, we also discuss new aspects of
      sodium balance, with particular attention to new observations on nonosmolar
      interstitial sodium storage.

PMID- 21175832
TI  - Trace minerals in patients with end-stage renal disease.
AB  - The kidneys are famously responsible for maintaining external balance of
      prevalent minerals, such as sodium, chloride, and potassium. The kidney's role in
      handling trace minerals is more obscure to most nephrologists. Similarly, the
      impact of kidney failure on trace mineral metabolism is difficult to anticipate.
      The associated dietary modifications and dialysis create the potential for trace
      mineral deficiencies and intoxications. Indeed, there are numerous reports of
      dialysis-associated mishaps causing mineral intoxication, notable for the
      challenge of assigning causation. Equally challenging has been the recognition of
      mineral deficiency syndromes, amid what is often a cacophony of multiple
      comorbidities that vie for the attention of clinicians who care for patients with
      chronic kidney disease. In this paper, I review a variety of minerals, some of
      which are required for maintenance of normal human physiology (the U.S. Food and
      Drug Administration's list of essential minerals), and some that have attracted
      attention in the care of dialysis patients. For each mineral, I will discuss its
      role in normal physiology and will review reported deficiency and toxicity
      states. I will point out the interesting inter-relationships between several of
      the elements. Finally, I will address the special concerns of aluminum and
      magnesium as they pertain to the dialysis population.

PMID- 21175834
TI  - Evaluation of adult kidney transplant candidates.
AB  - Important advances in immunosuppressive therapy and refinement in surgical
      techniques have allowed renal transplantation to become the treatment of choice
      for virtually all suitable candidates with end-stage renal disease. Compared to
      dialysis, kidney transplantation improves both patient survival and quality of
      life and, over time, can reduce the total cost of medical care. It must be noted,
      however, that although the risk of death in the first year after transplantation
      is <5%, not all patients qualify for the surgery because of their unacceptable
      risks for complications. The transplant evaluation process requires a
      comprehensive assessment of each patient's medical, surgical, and psychosocial
      histories. Selection of the suitable transplant candidate remains a challenge for
      transplant physicians owing, predominantly, to the presence of complex medical
      issues in the potential candidates and nonstandardized criteria for acceptance or
      rejection among transplant centers. Furthermore, with the ever-increasing
      disparity between donor organ supply and demand and resultant increased wait-list
      times, the transplant physicians must further consider the optimal management and
      re-evaluation of wait-list patients during the waiting period. This article
      describes a systematic approach for the evaluation of a potential renal
      transplant candidate. Various medical issues that arise during the evaluation
      process are discussed.

PMID- 21175835
TI  - Vascular access for dialysis in the United States: progress, hurdles,
      controversies, and the future.
AB  - In 2003, the Centers for Medicare and Medicaid Services (CMS) made an increase in
      arteriovenous fistula (AVF) prevalence and a decrease in catheter prevalence a
      priority, initiating a project known since 2005 as the Fistula First Breakthrough
      Initiative (FFBI). From 2003 to June 2010, the prevalent AVF in use rate has
      increased from 32.2% to 55.8% according to CMS data, a remarkable achievement yet
      short of CMS's 66% prevalent AVF goal. The prevalent catheter rate decreased from
      26.9% to 23.8% during this same period. Although an effort to augment AVF
      placement has resulted in issues of nonmaturation, the primary contributor to the
      23.8% prevalent catheter rate is the 82% incident catheter rate, which has not
      declined significantly. Future efforts to decrease the prevalent catheter rate
      and increase the prevalent AVF rate must be directed at patients with stages 4
      and 5 chronic kidney disease and the healthcare providers and practitioners
      involved in their care, including hospital systems, surgeons, referring
      physicians, and nephrologists. The nephrologist plays a key role in providing
      guidance to those providers and holding them accountable for improved vascular
      access outcomes.

PMID- 21175833
TI  - Survival disparities within American and Israeli dialysis populations: learning
      from similarities and distinctions across race and ethnicity.
AB  - There are counterintuitive but consistent observations that African American
      maintenance dialysis patients have greater survival despite their less favorable
      socioeconomic status, high burden of cardiovascular risks including hypertension
      and diabetes, and excessively high chronic kidney disease prevalence. The fact
      that such individuals have a number of risk factors for lower survival and yet
      live longer when undergoing dialysis treatment is puzzling. Similar findings have
      been made among Israeli maintenance dialysis patients, in that those who are
      ethnically Arab have higher end-stage renal disease but exhibit greater survival
      than Jewish Israelis. The juxtaposition of these two situations may provide
      valuable insights into racial/ethnic-based mechanisms of survival in chronic
      diseases. Survival advantages of African American dialysis patients may be
      explained by differences in nutritional status, inflammatory profile, dietary
      intake habits, body composition, bone and mineral disorders, mental health and
      coping status, dialysis treatment differences, and genetic differences among
      other factors. Prospective studies are needed to examine similar models in other
      countries and to investigate the potential causes of these paradoxes in these
      societies. Better understanding the roots of racial/ethnic survival differences
      may help improve outcomes in both patients with chronic kidney disease and other
      individuals with chronic disease states.

PMID- 21175836
TI  - Radiation exposure in dialysis access-related procedures decreases with increase
      in number of procedures performed by the interventional nephrologist.
AB  - An appreciation of the inherent risks with radiation exposure to patients and to
      the physician performing the procedure and the staff is urgently needed. The
      objective of this study is to assess radiation exposure to both patients and
      interventional nephrologists performing procedures and see any trends in the
      procedure and fluoroscopy times over a 2-year period. A total of 400 procedures
      performed at our vascular access center by a new to practice interventional
      nephrologist were recorded and retrospectively analyzed. Fluoroscopic time and
      procedure time for various procedures over the course of 2 years were recorded.
      This data were subsequently separated into eight groups (four quarters per year)
      based on the date of the procedure. Our study demonstrates a decrease in mean and
      median fluoroscopy times and procedure times for newly trained interventional
      with gain in number of procedures. The mean fluoroscopy time for the first two
      quarters was 5 minutes and 4 seconds, and the median was 3 minutes and 37
      seconds. The mean procedure time for the first two quarters was 38 minutes, and
      the median was 32 minutes. The mean fluoroscopy time for the last two quarters
      was 1 minute and 54 seconds, and the median was 1 minute and 26 seconds. The mean
      procedure time for the last two quarters was 27 minutes, and the median was 21
      minutes. In conclusion, gain of experience by the practicing Interventional
      Nephrologist from performing an increasing number of procedures leads to
      decreased procedure times and fluoroscopy times, which lowers the risk of
      radiation.

PMID- 21175837
TI  - Thrombectomy of arteriovenous dialysis grafts with early failure: is it
      worthwhile?
AB  - Arteriovenous dialysis grafts are prone to frequent thrombosis, which can be
      treated either percutaneously or surgically. To assess the outcomes of grafts
      treated for early thrombosis, we retrospectively queried a prospective,
      computerized database, and identified all grafts placed over a 5-year period that
      required thrombectomy within 60 days of creation. Technical success was defined
      as the immediate restoration of graft patency. Primary patency was calculated
      from thrombectomy to the next intervention, and cumulative graft survival from
      thrombectomy to permanent graft failure. Of 709 grafts placed, 98 grafts (14%)
      clotted within 60 days of creation, including 63 (9%) within 30 days of graft
      creation, and 35 (5%) at 31-60 days after creation. Most (95%) of grafts clotting
      within 30 days of creation underwent surgical thrombectomy, whereas 71% of those
      clotting at 31-60 days underwent percutaneous thrombectomy. The immediate
      technical success was 82% and 80% in grafts undergoing thrombectomy at <30 vs. 31
      60 days (p = 0.76). The median primary patency was 11 and 23 days (p = 0.46), and
      the median cumulative graft survival was 27 and 163 days, respectively (p =
      0.29). In conclusion, thrombectomy within 60 days of graft creation is associated
      with poor primary and cumulative graft patency, and may not be worthwhile.

PMID- 21175838
TI  - Safety of low volume iodinated contrast administration for arteriovenous fistula
      intervention in chronic kidney disease stage 4 or 5 utilizing a bicarbonate
      prophylaxis strategy.
AB  - Efforts to increase the number of functioning arteriovenous fistulas in chronic
      kidney disease (CKD) stages 4 and 5 have been impacted by concerns about the risk
      for contrast-induced nephropathy during diagnostic and interventional procedures
      for poorly developed fistulas. We conducted a prospective observational study of
      low volume iodinated contrast administration for fistulography and angioplasty in
      a CKD stage 4 and stage 5 population pretreated with a sodium bicarbonate
      protocol. Acute kidney injury was assessed by change in serum creatinine and
      urinary neutrophil-gelatinase associated lipocalcin (NGAL). Only 1/18 patients
      (5.5%) developed acute kidney injury as defined by change in serum creatinine 48
      hours after contrast exposure. No patients demonstrated significant change in
      urinary NGAL at 3 or 48 hours after procedure, nor did any require acute
      initiation of dialysis. Fistulography alone, or with angioplasty, utilizing a low
      volume of iodinated contrast and sodium bicarbonate solution for prophylaxis,
      appears to be safe in the CKD stages 4 and 5 population.

PMID- 21175839
TI  - Iatrogenic graft to vein fistula (GVF) formation associated with synthetic
      arteriovenous grafts.
AB  - The prevalence of fistulous connection between arteriovenous graft (AVG) and an
      adjacent vein resulting in graft-vein fistula (GVF) formation is not established.
      AVG venous outflow stenosis along with repeated and traumatic cannulation is
      likely major contributing factor of this complication. Detection and resolution
      of venous outflow stenosis may be the only needed intervention. We report a
      series of eight cases with GVF formation between AVG and adjacent veins.
      Awareness of this complication and intervention to relieve stenotic lesions may
      result in improved AVG survival.

PMID- 21175840
TI  - The catheter-challenged patient and the need to recognize the recurrently
      dysfunctional tunneled dialysis catheter.
AB  - Tunneled dialysis catheters (TDC) become dysfunctional because of placement
      problems, infection, thrombosis, and fibrin sheath formation. Occasional patients
      who are catheter dependant develop frequent catheter dysfunction because of
      thrombosis or thrombosis associated with fibrin sheath formation. This article
      attempts to define which dysfunctional catheters because of thrombosis and
      thrombosis associated with fibrin sheath formation actually represent a
      recurrently dysfunctional TDC (RDC) and puts forth an approach to managing the
      RDC.

PMID- 21175842
TI  - Effects of urbanization on occupancy of stream salamanders.
AB  - Urban development is the most common form of land conversion in the United
      States. Using a before-after control-impact study design, we investigated the
      effects of urbanization on larval and adult stages of southern two-lined
      salamanders (Eurycea cirrigera) and northern dusky salamanders (Desmognathus
      fuscus). Over 5 years, we estimated changes in occupancy and probabilities of
      colonization and survival in 13 stream catchments after urbanization and in 17
      catchments that were not urbanized. We also examined effects of proportion of
      urbanized area in a catchment and distance of the salamander population to the
      nearest stream on probabilities of colonization and survival. Before
      urbanization, adult and larval stages of the two salamander species occupied
      nearly all surveyed streams, with occupancy estimates ranging from 1.0 to 0.78.
      Four years after urbanization mean occupancy of larval and adult two-lined
      salamanders had decreased from 0.87 and 0.78 to 0.57 and 0.39, respectively.
      Estimates of mean occupancy of larval northern dusky salamanders decreased from
      1.0 to 0.57 in urban streams 4 years after urbanization; however, adult northern
      dusky salamander occupancy remained close to 1.0 in urban streams over 5 years.
      Occupancy estimates in control streams were similar for each species and stage
      over 5 years. Urbanization was associated with decreases in survival
      probabilities of adult and larval two-lined salamanders and decreases in
      colonization probabilities of larval dusky salamanders. Nevertheless, proportion
      of impervious surface and distance to nearest stream had little effect on
      probabilities of survival and colonization. Our results imply that in the
      evaluation of the effects of urbanization on species, such as amphibians, with
      complex life cycles, consideration of the effects of urbanization on both adult
      and larval stages is required.

PMID- 21175843
TI  - Balancing forest-regeneration probabilities and maintenance costs in dry
      grasslands of high conservation priority.
AB  - Abandonment of agricultural land has resulted in forest regeneration in species
      rich dry grasslands across European mountain regions and threatens conservation
      efforts in this vegetation type. To support national conservation strategies, we
      used a site-selection algorithm (MARXAN) to find optimum sets of floristic
      regions (reporting units) that contain grasslands of high conservation priority.
      We sought optimum sets that would accommodate 136 important dry-grassland species
      and that would minimize forest regeneration and costs of management needed to
      forestall predicted forest regeneration. We did not consider other conservation
      elements of dry grasslands, such as animal species richness, cultural heritage,
      and changes due to climate change. Optimal sets that included 95-100% of the dry
      grassland species encompassed an average of 56-59 floristic regions (standard
      deviation, SD 5). This is about 15% of approximately 400 floristic regions that
      contain dry-grassland sites and translates to 4800-5300 ha of dry grassland out
      of a total of approximately 23,000 ha for the entire study area. Projected costs
      to manage the grasslands in these optimum sets ranged from CHF (Swiss francs) 5.2
      to 6.0 million/year. This is only 15-20% of the current total estimated cost of
      approximately CHF30-45 million/year required if all dry grasslands were to be
      protected. The grasslands of the optimal sets may be viewed as core sites in a
      national conservation strategy.

PMID- 21175844
TI  - Engaging the recreational angling community to implement and manage aquatic
      protected areas.
AB  - Recreational angling is a popular leisure activity, the quality of which is
      greatly dependent on fish abundance and well-functioning aquatic ecosystems.
      Aquatic protected areas (APAs) are used to help maintain and even restore aquatic
      systems and their associated biota, including fish species that are popular with
      recreational anglers. Paradoxically, the use of APAs has been a source of much
      contention and conflict between members of the recreational angling community and
      those interested in or mandated to protect aquatic resources on the basis of the
      interests of multiple stakeholder groups. The angling community is concerned
      about the loss of fishing opportunities and effectiveness of APAs. Although it is
      still unclear whether establishment of APAs alone can effectively protect aquatic
      resources, actively including the recreational angling community in the design,
      implementation, and management of APAs will help ensure the values of this rather
      substantial user group are incorporated into aquatic conservation strategies.
      Conversely, the probability of increasing the sustainability of recreational
      angling and related economies will be greatest if recreational angler groups
      remain open minded to both short-term and long-term goals of fisheries
      conservation strategies, including the use of APAs.

PMID- 21175845
TI  - Intracoronary compared to intravenous bolus abciximab during primary percutaneous
      coronary intervention in ST-segment Elevation Myocardial Infarction (STEMI)
      patients reduces 30-day mortality and target vessel revascularization: a
      randomized trial.
AB  - BACKGROUND:  Abciximab is beneficial in patients with ST-segment elevation
      myocardial infarction (STEMI) undergoing primary percutaneous coronary
      intervention (pPCI). However, the optimal administration route of the initial
      bolus of abciximab, that is, intravenous (IV) versus intracoronary (IC), has been
      questioned. Preliminary studies suggest that IC-bolus is superior, probably due
      to high local concentration. In this study, we assess the short-term efficacy and
      safety of IC compared to IV bolus of abciximab in patients with STEMI during
      pPCI. METHODS:  In 2006-2008, we randomized 355 STEMI patients who underwent pPCI
      and had indication for abciximab to either IV or IC bolus followed by a 12-hour
      IV infusion. Primary end-points at 30 days were target vessel revascularization
      (TVR), recurrent myocardial infarction (MI) or death, and the composite of the
      three. Secondary end-points were bleeding complications. RESULTS:  The two groups
      (IV n = 170;IC n = 185) were similar with respect to baseline characteristics.
      Mortality at 30 days was 5.3% in the IV group compared to only 1.1% in the IC
      group (P = 0.02). TVR was performed in 9.4% in the IV group compared to 3.8% in
      the IC group (P = 0.03). No significant difference in MI rates was seen (IV 4.7%
      vs. IC 2.7%; P = 0.32). We found a significant reduction in the composite end
      point (IV 19.4% vs. IC 7.6%; P = 0.001) in favor of IC use. Major bleeding
      complications were similar (IV 2.4% vs. IC 1.6%; P = 0.62). Neither difference
      was observed in minor bleedings (IV 14.1% vs. IC 9.7%; P = 0.20). CONCLUSION:  IC
      administration of bolus abciximab in STEMI patients undergoing pPCI reduces 30
      day mortality and TVR and tends to reduce MI, compared to IV-bolus.

PMID- 21175846
TI  - Hepatopulmonary syndrome in children - is conventional liver transplantation
      always needed?
AB  - BACKGROUND: Hepatopulmonary syndrome (HPS) is the association of liver disease,
      hypoxemia, and intrapulmonary vascular dilatations. There are little data on the
      management of HPS in children other than conventional orthotopic liver
      transplantation (OLT). AIMS: To describe the patient characteristics, mode of
      diagnosis, treatment, and outcomes of children with HPS at our center. METHODS:
      Retrospective review of patients diagnosed with HPS between 1997 and 2007 after
      IRB approval. RESULTS: There were 10 patients, six females; median age at
      diagnosis of HPS was 12 yr. Six with cirrhosis underwent OLT and had subsequent
      resolution of HPS and are stable at last follow-up. Of the remaining four, two
      had cirrhosis. HPS resolved without conventional OLT in the following four
      patients: hepatitis C after antiviral treatment, biliary atresia with portal
      hypertension after transjugular intrahepatic portosystemic shunting, Abernethy
      syndrome after auxiliary partial OLT, and in a child with splenic vein thrombosis
      after splenectomy. CONCLUSIONS: Our series shows resolution of HPS in all
      patients and 100% survival after conventional OLT. Four children had resolution
      of HPS after surgical or medical treatments other than conventional OLT. Careful
      review of clinical status and underlying pathophysiology and anatomy at diagnosis
      of HPS should inform treatment decisions.

PMID- 21175847
TI  - Factors associated with positive attitudes toward organ donation in Arab
      Americans.
AB  - BACKGROUND: The demand for transplantable organ continues to exceed supply,
      particularly in minority patient populations. We explored the factors influencing
      organ donation attitude within the Arab American community. METHODS: Secondary
      data analysis from a face-to-face survey administered in late 2003 to 1016 adults
      from a representative population-based sample on Greater Detroit Arab Americans.
      RESULTS: Christian Arab Americans were more likely than Muslim Arab Americans,
      and women more than men, to believe organ donation after death was justifiable.
      Higher educational attainment and income, as well as greater acculturation into
      American society, were associated with greater odds of believing organ donation
      to be justified. Self-reported health status and level of psychological distress
      and health insurance status were not associated with beliefs about organ
      donation. CONCLUSIONS: A multifaceted approach toward increasing organ donation
      rates in this growing population requires targeted community-health care system
      collaborations involving religious and civic leaders using Arabic language and
      culturally sensitive media. SUMMARY: Arab Americans represent a growing
      population about which little is known in regard to organ donation and
      transplantation. This population is not specifically captured within national and
      local transplantation databases, and little empiric work has assessed attitudes
      and barriers toward organ donation and transplantation within this community. Our
      work represents the first to use a representative population-based sample to
      explore the modifiable and non-modifiable characteristics of those who believe
      cadaveric organ donation to be justified.

PMID- 21175848
TI  - Risk factors for development of new-onset diabetes mellitus after transplant in
      adult lung transplant recipients.
AB  - The objectives of this study are to examine the incidence of new-onset diabetes
      mellitus after transplant (NODAT) and to identify its risk factors in adult lung
      transplant recipients using the Organ Procurement and Transplant Network/United
      Network of Organ Sharing database. Between July 2004 and December 2007, a total
      of 3540 adults (>=18 yr old) received their first single- or double-lung
      transplant alone and had at least one follow-up report of post-transplant
      diabetic status. Among these, 2991 recipients were identified as not having
      diabetes mellitus (DM) pre-transplant. Risk factors for NODAT were examined. DM
      was newly reported in 33.4% of the 2991 recipients over the median follow-up time
      of 670 d. Significant independent risk factors for the development of NODAT
      included male gender (HR = 1.15), recipient age >=50 (1.46), African American
      (1.39), higher body mass index (1.51 for >=30 vs. 18-25), cystic fibrosis (3.30),
      and tacrolimus use at discharge (1.67). NODAT occurred in a third of adult lung
      transplant recipients during the median follow-up period. Some of the risk
      factors for NODAT after lung transplant are similar to those reported in other
      solid-organ transplants. Cystic fibrosis is a strong risk factor for development
      of NODAT after lung transplant.

PMID- 21175849
TI  - The low dose of rituximab in ABO-incompatible kidney transplantation without a
      splenectomy: a single-center experience.
AB  - PURPOSE: A new protocol for ABO-incompatible (ABO-i) kidney transplantation
      including rituximab was introduced in January 2005 in our institute. This study
      reviewed the results and evaluated the use of low-dose rituximab in ABO-i kidney
      transplantation. MATERIAL AND METHODS: Seventy-four de novo ABO-i kidney
      transplantations were performed at Tokyo Women's Medical University between
      January 2005 and August 2010. The immunosuppressive protocol was consisting of
      tacrolimus, mycophenolate mofetil, and methylprednisolone. All the patients
      received induction therapy with basiliximab. The pre-conditioning protocol
      included double-filtration plasmapheresis and a single dose of rituximab. A dose
      of 500 mg/body rituximab was initially employed and yielded excellent results
      (Group I, n = 24). Afterward, the dose of rituximab was reduced to 200 mg/body in
      January 2007 (Group II, n = 50). RESULTS: Seventy-four de novo ABO-i recipients
      were treated with this protocol, and all patients underwent kidney
      transplantation successfully. Effective elimination of the peripheral blood CD19
      cells was observed in both groups. However, the peripheral blood CD19 levels were
      still low in both groups at 24 months after treatment. CONCLUSION: The patients
      in Group II showed excellent results similar to Group I. These results suggest
      that the low dose of rituximab (200 mg/body) is the sufficient dose in ABO-i
      kidney transplantation.

PMID- 21175850
TI  - Challenges of multiple mutations in individual patients with haemophilia.
AB  - Multiple mutations in the same gene within a haemophilia family are being
      increasingly reported and raise many issues with regard to the specificity of the
      mutations in causing the disease. In a proportion of families with multiple
      mutations, discordant phenotypic severity is often observed among the affected
      members. Understanding whether these mutations influence additively or non
      additively the structure, stability and function of the protein will help in a
      better clinical evaluation of these patients. In case of haemophilia A, out of
      2740 entries, ten are double mutants. Among the 2891 patient entries in the
      Haemophilia B mutation database, there are 34 double mutants and one triple
      mutant. The major challenge in patients with multiple mutations lies in genetic
      diagnosis and counselling especially in developing countries wherein the entire
      gene is not being sequenced and the screening is stopped as soon as the mutation
      is identified. As of now, the presence of multiple mutations stresses the
      importance of additional DNA testing in patients with known mutations who have
      unusual phenotypes or additional, unexplained clinical problems, until more cost
      effective techniques for screening the entire gene are identified.

PMID- 21175851
TI  - Two novel mutations in the SLC40A1 and HFE genes implicated in iron overload in a
      Spanish man.
AB  - The most common form of hemochromatosis is caused by mutations in the HFE gene.
      Rare forms of the disease are caused by mutations in other genes. We present a
      patient with hyperferritinemia and iron overload, and facial flushing. Magnetic
      resonance imaging was performed to measure hepatic iron overload, and a molecular
      study of the genes involved in iron metabolism was undertaken. The iron overload
      was similar to that observed in HFE hemochromatosis, and the patient was double
      heterozygous for two novel mutations, c.-20G>A and c.718A>G (p.K240E), in the HFE
      and ferroportin (FPN1 or SLC40A1) genes, respectively. Hyperferritinemia and
      facial flushing improved after phlebotomy. Two of the patient's children were
      also studied, and the daughter was heterozygous for the mutation in the SLC40A1
      gene, although she did not have hyperferritinemia. The patient presented a mild
      iron overload phenotype probably because of the two novel mutations in the HFE
      and SLC40A1 genes.

PMID- 21175852
TI  - Biosimilar agents in oncology/haematology: from approval to practice.
AB  - The regulation of biosimilars is a process that is still developing. In Europe,
      guidance regarding the approval and use of biosimilars has evolved with the
      products under consideration. It is now more than 3 years since the first
      biosimilar agents in oncology support, erythropoiesis-stimulating agents, were
      approved in the EU. More recently, biosimilar granulocyte colony-stimulating
      factors have received marketing approval in Europe. This review considers general
      issues surrounding the introduction of biosimilars and highlights current
      specific issues pertinent to their use in clinical practice in oncology.
      Information on marketing approval, extrapolation, labelling, substitution,
      immunogenicity and traceability of each biosimilar product is important,
      especially in oncology where patients are treated in repeated therapy courses,
      often with complicated protocols, and where biosimilars are not used as a unique
      therapy for replacement of e.g. growth hormone or insulin. While future
      developments in the regulation of biosimilars will need to address multiple
      issues, in the interim physicians should remain aware of the inherent differences
      between biosimilar and innovator products.

PMID- 21175853
TI  - Scleredema treated with broad-band ultraviolet A phototherapy plus colchicine.
AB  - Scleredema is an uncommon condition characterized by induration of skin. The
      pathogenesis is not known, although the increased expression of collagen
      producing fibroblasts in the skin has been demonstrated. Scleredema has been
      difficult to treat with scattered reports of success with bath psoralen plus
      ultraviolet A (PUVA), cream PUVA, UVA1 and others. The use of low-dose broad-band
      UVA phototherapy was found to be effective in the treatment of morphea.
      Colchicine has been shown to interfere with collagen synthesis and is used
      successfully in scleroderma. We report the first case of scleredema that improved
      markedly with low-dose broad-band UVA plus colchicine treatment.

PMID- 21175854
TI  - Photoaggravated hand and foot psoriasis.
AB  - The majority of patients with psoriasis benefit from ultraviolet radiation
      exposure, but psoriasis can deteriorate on exposure to sunlight in some people.
      We report a patient with longstanding palmoplantar psoriasis that showed an
      unusual evolution into photoaggravated psoriasis, with change of distribution
      from the palmar to the dorsal aspect of the hands, and confirmation by
      photoprovocation with solar-simulated radiation. The onset of photosensitivity
      should be suspected in patients with hand and foot psoriasis showing a similar
      change in distribution.

PMID- 21175856
TI  - Recent onset vitiligo on acral areas treated with phototherapy: need of early
      treatment.
AB  - In vitiligo, the effect of phototherapy depends on lesional location. While face
      and neck lesions generally show good responses, acral areas are resistant to
      phototherapy. We describe two cases of recent onset vitiligo on acral areas that
      showed an excellent response with phototherapy. These results suggest that even
      acral areas in vitiligo can be markedly improved by phototherapy if it has a
      recent onset.

PMID- 21175855
TI  - Merkel cell carcinoma arising in immunosuppressed patients treated with high-dose
      ultraviolet A1 (320-400 nm) phototherapy: a report of two cases.
AB  - Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumour of the skin.
      Though immunodeficiency is the most relevant risk factor, ultraviolet (UV)
      radiation is also involved, but as of yet we do not know the action spectrum,
      pattern or dose which would produce a dangerous exposure. A retrospective study
      of two immunosuppressed patients who developed MCC during, or soon after a
      treatment cycle with high dose UVA1 exposures was conducted, in order to
      understand wether repeated exposures to suberythemogenic UVA1 radiation may have
      a cancerogenic activity provoking MCC in immunosuppressed patients.

PMID- 21175857
TI  - Complete resolution of a squamous cell carcinoma of the skin using intralesional
      5-aminolevulinic acid photodynamic therapy intralesional PDT for SCC.
AB  - We present an 82-year-old female patient with a 2-year history of an infiltrative
      squamous cell carcinoma (SCC) on her right cheek. The patient was treated with
      one intralesional photodynamic therapy (PDT) session using 10% 5-aminolevulinic
      acid solution. We used red light by a non-coherent light source at a light dose
      of 100 J/cm2 and a fluency rate of 100 mW/cm2. Complete clinical and histological
      response was achieved 3 months after the treatment procedure. Cosmetic outcome
      was evaluated as fair. The patient remains disease free with the absence of any
      clinical sign of recurrence 16 months after PDT. Long-term follow-up is needed
      for assessment of recurrences. Optimization of the therapeutic protocol, as well
      as justification of our results in larger studies are needed in order to elicit
      safe conclusions.

PMID- 21175858
TI  - Commercial devices measuring UV radiation: a good choice for the public?
AB  - Commercial devices measuring UV radiation are available on the market at
      affordable prices. This work presents the response of six commercial devices in
      comparison to UV index measurements and in relation to the guidelines provided by
      the INTERSUN programme. Taking everything into account, overestimated or non
      standard data, and ambiguous or incomplete information was found. Instead of
      using these gadgets, people should refer to official information and advice
      provided by health and weather services.

PMID- 21175859
TI  - Granulomatous tattoo reaction induced by intense pulse light treatment.
AB  - Cosmetic tattooing involves implantation of pigments into the dermis in order to
      create a permanent makeup. Here, we report a case of sarcoidal granulomatous
      reaction to old cosmetic tattoos after an intense pulsed light (IPL) treatment
      for facial skin rejuvenation. We consider this case as a peculiar example of
      photo-induced reaction to tattoo. In addition, we hypothesize that an underlying
      immune dysfunction was present, and acted as a predisposing factor for this
      unusual response, as the patient had suffered from an episode of acute pulmonary
      sarcoidosis 15 years before. Overall, our observation suggests that IPL treatment
      should be used cautiously in patients with tattoos, especially when a history of
      autoimmune disease is present.

PMID- 21175860
TI  - Primary epithelioid hemangioendothelioma in the clival region: a case report and
      literature review.
AB  - Epithelioid hemangioendothelioma (EHE) is a rare and low-grade vascular tumor,
      which usually occurs in the soft tissue, liver, breast, lung and skeleton. Here
      we submit a case with EHE of the clival region. A 58-year-old woman was admitted
      with a medical history of 3 months headache and 1 month visual deterioration. MRI
      revealed a well-circumscribed mass of 4.0 cm * 3.0 cm with bony invasion. The
      tumor was subtotally removed in a piecemeal fashion. Histologically, the tumor
      was composed of epithelioid cells with eosinophilic cytoplasm and
      intracytoplasmic vacuoles. Immunohistochemically, the tumor cells were positive
      for the markers CD31, CD34, factor VIII and vimentin. The pathological result was
      interpretated as EHE of the clival region. EHE is an uncommon vascular tumor,
      which is rarely seen in the clival region. Definitive diagnosis depends on
      histopathologic and immunohistochemical features.

PMID- 21175861
TI  - An autopsy case of MM2-cortical + thalamic-type sporadic Creutzfeldt-Jakob
      disease.
AB  - A 59-year-old Japanese man presented with depressed mood, insomnia, abnormal
      behavior and dementia. Visual and gait disturbance with ataxia also developed.
      Diffusion-weighted MRI showed widespread regions of hyperintensity in the
      bilateral cerebral cortex. The patient died at 62 after a progressive clinical
      course of 32 months. Myoclonus, periodic sharp-wave complexes on EEG, and
      akinetic mutism state were not observed. Neuropathologic examination showed
      widespread cerebral neocortical involvement with both large confluent vacuole
      type, alongside fine vacuole-type spongiform changes. Mild spongiform
      degeneration was observed in the striatum and lateral thalamus. Severe neuron
      loss with hypertrophic astrocytosis in the medial thalamus and inferior olivary
      nucleus was present. Cerebral white matter showed diffuse myelin pallor
      indicating panencephalopathic-type pathology. In the cerebellar cortex, severe
      Purkinje neuron loss was observed, but no spongiform degeneration in the
      molecular layer or neuron loss in the granular cell layer. PrP immunostaining
      showed widespread perivacuolar-type PrP, irregular plaque-like PrP, and synaptic
      type PrP depositions in the cerebral neocortex. Mild PrP deposition was observed
      in the striatum, lateral thalamus and brainstem, whereas PrP deposition was not
      apparent in the medial thalamus and inferior olivary nucleus. PrP gene analysis
      showed no mutations, and methionine homozygosity was observed at codon 129.
      Western blot analysis of protease-resistant PrP showed type 2 PrP pattern. MRI
      and cerebral neocortical pathology suggested MM2-cortical-type sporadic
      Creutzfeldt-Jakob disease (sCJD), whereas the clinical course and pathology of
      the medial thalamus and inferior olivary nucleus suggested MM2-thalamic-type
      sCJD. We believe this was a combination of MM2-cortical-type and MM2-thalamic
      type sCJD, which explains the broad spectrum of MM2-type sCJD findings and
      symptoms.

PMID- 21175862
TI  - Human embryonic neural stem cell transplantation increases subventricular zone
      cell proliferation and promotes peri-infarct angiogenesis after focal cerebral
      ischemia.
AB  - Neurogenesis and angiogenesis are two important processes that may contribute to
      the repair of brain injury after stroke. This study was designed to investigate
      whether transplantation of human embryonic neural stem cells (NSCs) into cortical
      peri-infarction 24h after ischemia effects cell proliferation in the
      subventricular zone (SVZ) and angiogenesis in the peri-infarct zone. NSCs were
      prepared from embryonic human brains at 8 weeks gestation. Focal cerebral
      ischemia was induced by permanent occlusion of the middle cerebral artery of
      adult rats. Animals were randomly divided into two groups (n=30, each) at 24h
      after ischemia: NSC-grafted and medium-grafted groups. Toluidine blue staining
      and 5'-bromo-2'-deoxyuridine (BrdU) or von Willebrand factor (vWF)
      immunohistochemistry were performed at 7, 14 and 28 days after transplantation.
      NSC transplantation increased the number of BrdU-positive cells in the ischemic
      ipsilateral SVZ compared with the medium control at 7 days (P<0.01). This
      difference in SVZ cell proliferation persisted at 14 days (P<0.01), but was not
      significant at 28 days (P>0.05). In addition, angiogenesis, as indicated by BrdU
      and vWF staining in cortical peri-infarct regions, was augmented by 46% and 65%
      in NSC-grafted rats versus medium-grafted rats at 7 and 14 days, respectively
      (P<0.05). However, this increase became non-significant at 28 days (P>0.05). Our
      results indicate that NSC transplantation enhances endogenous cell proliferation
      in the SVZ and promotes angiogenesis in the peri-infarct zone, even if it is
      performed in the acute phase of ischemic injury.

PMID- 21175863
TI  - Intravenous immunoglobulin therapy prevents development of autoimmune
      encephalomyelitis and suppresses activation of matrix metalloproteinases.
AB  - Although intravenous immunoglobulin (IVIG) has been reported to improve the
      status of expanded disability status scale (EDSS) of multiple sclerosis (MS)
      patients and reduce the annual relapse rate, some studies did not find its
      beneficial effects. In the present study, using an animal model for MS, we found
      that prophylactic, but not therapeutic, treatment successfully suppressed the
      disease development. During the search for factors involved in the disease
      suppression by IVIG, we obtained evidence suggesting that IVIG exerts its
      function, at least in part, by suppressing activation of matrix
      metalloproteinases (MMP)-2 and -9. Gelatin zymography revealed that gelatinase
      activities were suppressed by IVIG treatment in the spinal cord, but not in
      plasma. This finding raises the possibility that IVIG blocks MMP activities at
      the interface between the blood stream and CNS. With in situ zymography, we also
      observed that gelatinase activities were expressed mainly in astrocytes in the
      inflamed spinal cord of control rats and that this expression was attenuated by
      the treatment. These findings provide useful information to set optimal
      conditions for IVIG treatment of MS and to obtain more beneficial effects.

PMID- 21175864
TI  - Enhancement of native and phosphorylated TDP-43 immunoreactivity by proteinase K
      treatment following autoclave heating.
AB  - TDP-43 is a major disease protein in amyotrophic lateral sclerosis (ALS) and
      frontotemporal lobar degeneration with TDP-43 (FTLD-TDP). To evaluate the
      effectiveness of proteinase K (PK) treatment in antigen retrieval for native and
      phosphorylated TDP-43 protein, we examined the temporal cortex and spinal cord
      from patients with sporadic ALS and FTLD-TDP and control subjects. PK treatment
      following heat retrieval enhanced the immunoreactivity for native TDP-43 in
      controls as well as for native and phosphorylated TDP-43 in ALS and FTLD-TDP. A
      significant number of TDP-43-positive neuropil threads were demonstrated in
      lesions, in which routine immunohistochemistry revealed that the predominant
      inclusions are cytoplasmic. This retrieval method is the best of
      immunohistochemical techniques for demonstrating TDP-43 pathology, especially in
      the neuropil.

PMID- 21175865
TI  - Impact of insulin resistance, insulin and adiponectin on kidney stones in the
      Japanese population.
AB  - OBJECTIVES: It has been reported that kidney stones are linked to metabolic
      syndrome (MetS), which is characterized by insulin resistance. The aim of the
      present study was to examine the association of insulin resistance, insulin and
      adiponectin with kidney stones in a Japanese population. METHODS: From February
      2007 to March 2008, 1036 (529 men and 507 women) apparently healthy Japanese
      subjects, aged 35-79 years, were analyzed. Weight, height, waist circumference
      and blood pressure were measured. Overnight fasting blood was collected to
      measure insulin and adiponectin levels. Homeostasis model assessment of insulin
      resistance (HOMA-IR) was calculated to assess insulin resistance. Logistic
      regression analysis was used to estimate the odds ratio (OR) and 95% confidence
      intervals for a self-reported history of kidney stones across tertiles of HOMA
      IR, insulin and adiponectin. RESULTS: Of the participants, 84 men (15.6%) and 35
      women (6.9%) had a history of kidney stones. Age, body mass index, waist
      circumference, systolic and diastolic blood pressures, HOMA-IR and insulin were
      significantly higher in women with than in women without kidney stones. There was
      no difference in adiponectin level between subjects with and without a history of
      kidney stones in either sex. Furthermore, a significant positive trend was
      observed in the age-adjusted OR for a history of kidney stones across insulin
      tertiles (P-value for trend = 0.04) in women. CONCLUSIONS: For Japanese women,
      HOMA-IR and insulin are associated with a history of kidney stones. The findings
      suggest that MetS components could increase the risk of kidney stones through
      subclinical hyperinsulinemia and insulin resistance.

PMID- 21175866
TI  - More scientific evidence for the therapeutic benefit of hydrotherapy in Avene.

PMID- 21175867
TI  - Avene Thermal Spring Water: an active component with specific properties.
AB  - Avene Thermal Spring Water (TSW) is a natural active component characterized by a
      low mineral content. In vitro experiments have demonstrated the effect of Avene
      TSW on membrane fluidity, its antiradical and anti-inflammatory properties, its
      effects on many mediators involved in the immune response and its stimulating
      effect on keratinocyte differentiation. The clinical efficacy of the water was
      demonstrated at the hydrotherapy centre in chronic and disabling diseases such as
      atopic dermatitis but also in various settings in medical and post dermatology
      procedure such as photodynamic therapy or photothermolysis. All these data
      support the fact that the Avene TSW is an active component.

PMID- 21175868
TI  - Inhibition of TNF-alpha induced-adhesion molecules by Avene Thermal Spring Water
      in human endothelial cells.
AB  - BACKGROUND: Cell adhesion molecules, such as E-selectin or intercellular adhesion
      molecule 1 (ICAM-1), play an important role in mediating leucocyte capture and
      rolling on the surface of blood vessels in atopic skin. The effectiveness of
      Avene hydrotherapy in patients suffering from atopic dermatitis has previously
      been demonstrated. Thus, we examined the effect of Avene Thermal Spring Water
      (TSW) on adhesion molecules to understand its mechanism of action. METHODS: Human
      endothelial cells EA.hy926 were treated with tumour necrosis factor-alpha
      (TNFalpha) in the presence or not of Avene TSW during 4 h. As nuclear factor
      kappaB (NF-kappaB) is involved in the signalisation of inflammatory mediators
      such as the adhesion molecules, the translocation of NF-kappaB in endothelial
      cells was assessed by immunohistochemistry with anti-NF-kappaBp65. The protein
      and mRNA levels of TNFalpha-induced ICAM-1 and E-selectin were assessed by ELISA
      assay and RT-PCR. These adhesion molecules were also detected by
      immunohistochemistry. RESULTS: Tumour necrosis factor-alpha induced the
      activation of p65 NF-kappaB nuclear translocation. TNFalpha also induced E
      selectin and ICAM-1 in a dose-dependant manner in EA.hy926 endothelial cells. In
      the presence of Avene TSW, a significant inhibition of the TNFalpha-induced E
      selectin and ICAM-1 expression (-22% and -7%, respectively, P < 0.05) was
      observed. CONCLUSION: These data suggest that Avene TSW mediated inhibition of
      TNFalpha-induced E-selectin and ICAM-1 expression. The inhibition of such
      adhesion molecules is attributable to the suppression of NF-kappaB transcription
      factor pathway activation.

PMID- 21175869
TI  - Acceleration of keratinocyte differentiation by transient receptor potential
      vanilloid (TRPV6) channel activation.
AB  - BACKGROUND: Numerous studies have demonstrated the beneficial effect of Avene
      Thermal Spring Water (TSW) in dermatological diseases but the molecular
      mechanisms remain unknown. The objective of the present study was to evaluate the
      effect of Avene TSW on the morphological and molecular features related to the
      more advanced status of differentiation of human keratinocytes. MATERIAL AND
      METHODS: Normal human keratinocytes (NHK) were differentiated in medium powder
      reconstituted with Avene TSW and assessed by RT-PCR and immunohistochemistry.
      Calcium entry was measured by a Fura-2 AM probe. TRPV6 channel were detected by
      immunohistochemistry, RT-PCR and western blot. RESULTS: Treatment of NHK with
      Avene TSW led to an enhanced constitutive calcium entry that resulted in the
      increased expression of involucrin and cytokeratins 1 and 10. This enhanced
      constitutive calcium entry in Avene TSW-treated keratinocytes was mediated by the
      TRPV6 calcium channel. Moreover, Avene TSW-mediated calcium entry was due to the
      increase in TRPV6 expression as well as the channel abundance at the cell
      membrane. CONCLUSIONS: An other mechanism of action of Avene TSW is described.
      Avene TSW treatment induced an enhanced constitutive calcium entry mediated by
      TRPV6 channel leading to the acceleration of human keratinocytes differentiation.

PMID- 21175870
TI  - Modulation of Interleukin-8 and staphylococcal flora by Avene hydrotherapy in
      patients suffering from chronic inflammatory dermatoses.
AB  - BACKGROUND: A number of studies argue in favour of an important role of microbial
      colonization, in particular of Staphylococcus aureus, in triggering atopic
      dermatitis (AD) flare-up and psoriasis, in particular through the superantigenic
      properties of toxins generated by S. aureus. OBJECTIVES: The aim of this study
      was to assess the efficacy of a 3-week Avene hydrotherapy on the skin surface of
      patients suffering from psoriasis or atopic dermatitis. METHODS: Skin samples
      were taken from healthy subjects or atopic (n = 18) or psoriatic patients (n =
      39) undergoing hydrotherapy at Avene at the beginning (D0) and the end of
      treatment (D18). The severity of the dermatosis was evaluated according to
      SCORing Atopic Dermatitis (SCORAD) or Psoriasis Area Severity Index (PASI) scores
      at D0 and D18. Marker of inflammation interleukin 8 (IL-8), S. aureus
      colonization (protein A) and enterotoxins were assessed in skin samples using RT
      PCR. RESULTS: At D0, significant differences were observed between healthy
      subjects and atopic or psoriatic patients in all the parameters evaluated (IL-8,
      protein A). At the end of the hydrotherapy, a significant decrease in SCORAD was
      associated with a significant reduction of IL-8, S. aureus colonization and
      enterotoxin D in patients with atopic dermatitis. Similarly, a significant
      decrease in PASI was associated with a significant reduction of IL-8, S. aureus
      colonization and enterotoxin N in patients with psoriasis. CONCLUSIONS: This
      study demonstrates the positive effects of Avene hydrotherapy on the skin of
      patients suffering from chronic dermatosis, with decreased inflammation and
      reduced colonization by S. aureus.

PMID- 21175871
TI  - Impact of Avene hydrotherapy on the quality of life of atopic and psoriatic
      patients.
AB  - BACKGROUND: Atopic dermatitis and psoriasis engender a significant deterioration
      in patients' quality of life. Although the efficacy of patient management at the
      Avene hydrotherapy centre has been demonstrated by clinical studies, few data
      relating to changes in the quality of life following therapeutic management are
      available. The objective of this study was to evaluate the short- and medium-term
      effects of hydrotherapy not only on the patients' quality of life, but also on
      the quality of life of the parents of the treated children. METHODS: In this 6
      month longitudinal observational study, adult (n = 174) and paediatric (n = 212)
      atopic patients and psoriatic patients (n = 262) had to complete questionnaires
      relating to the quality of life at the beginning (D0) and after 3 weeks
      hydrotherapy (W3), and then, 3 (M3) and 6 months (M6) later. The dermatology life
      quality index (DLQI) and the Short-Form-12 Health Survey (SF-12) generic
      questionnaire were given to adult patients. The children's dermatological life
      quality index (CDLQI) was given to paediatric patients, and the SF-12 to their
      parents. RESULTS: At D0, the DLQI score was 29.7 +/- 20.1 and 26.9 +/- 18.9 for
      atopic and psoriatic patients, respectively. At W3, this score had decreased
      significantly to reach 16.8 +/- 14.9 (P < 0.01) and 10.0 +/- 10.5 (P < 0.001) for
      atopic and psoriatic patients, respectively. The DLQI scores at M3 and M6 were
      20.7 +/- 16.4 and 23.1 +/- 18.8 for atopic patients and 18.8 +/- 16.7 and 21.9 +/
      19.6 for psoriatic patients and remained significantly lower in comparison with
      D0 values (P < 0.05). CONCLUSION: A 3-week course of treatment at the Avene
      hydrotherapy centre significantly improved the quality of life of patients
      suffering from skin diseases. This improvement persisted 3 and 6 months after
      management by hydrotherapy.

PMID- 21175872
TI  - Clinical efficacy of Avene hydrotherapy measured in a large cohort of more than
      10,000 atopic or psoriatic patients.
AB  - BACKGROUND: Atopic dermatitis (AD) and psoriasis are chronic skin conditions.
      Local or systemic treatments are effective, but their effects are transient.
      Hydrotherapy, used alone or in combination with other treatments, could be
      considered as one form of care in providing effective management of these
      dermatoses. The objective of this observational study was to evaluate the benefit
      of a 3-week treatment at Avene Hydrotherapy Centre in a very large cohort of
      patients suffering from atopic dermatitis and psoriasis and to assess the
      treatment benefits on patients undergoing hydrotherapy for two consecutive years.
      METHODS: This 8-year observational study analysed 14,328 records of patients
      having a dermatological disease and who came to Avene Hydrotherapy Centre for a 3
      week treatment between 2001 and 2009. Among them, patients were suffering from
      atopic dermatitis (n = 5916) and psoriasis (n = 4887). On admission on D0 (day 0)
      and at the end of cure on D18 (day 18), the severity of AD and psoriasis were
      evaluated by SCORing Atopic Dermatitis (SCORAD) and Psoriasis Area and Severity
      Index (PASI), respectively. In order to assess the cumulative effect of the
      hydrotherapy treatment, the evolution of SCORAD or PASI of patients who came 2
      years in a row was also calculated. RESULTS: A significant improvement in SCORAD
      was observed between D0 and D18 (-41.6%) (P < 0.0001) and similarly, a
      significant reduction in PASI was noted between D0 and D18 (-54.4%) (P < 0.0001)
      after 3-weeks of hydrotherapy. PASI 50 and PASI 75 were 64.3% and 19.5%,
      respectively. For atopic patients (n = 1102) or patients suffering from psoriasis
      (n = 833) who came for two consecutive years, a significant SCORAD and PASI
      improvement was observed on D0 of the second year when compared with D0 of the
      previous year (P < 0.0001). CONCLUSIONS: This study is the first observational
      study in such a large cohort demonstrating the benefit of a 3-week treatment at
      the Avene Hydrotherapy Centre for atopic and psoriatic patients.

PMID- 21175873
TI  - Pimecrolimus 1% cream for oral erosive lichen planus: a 6-week randomized, double
      blind, vehicle-controlled study with a 6-week open-label extension to assess
      efficacy and safety.
AB  - OBJECTIVE: To assess the efficacy and safety of topical pimecrolimus 1% cream in
      the treatment of oral erosive lichen planus. DESIGN: A 6-week randomized, double
      blind, vehicle-controlled phase followed by a 6-week open-label phase. SETTING:
      Outpatients of the Department of Dermatology, University of Utah. PATIENTS:
      Twenty-one patients with oral erosive lichen planus were randomized and treated
      with either pimecrolimus 1% cream or vehicle cream. INTERVENTION: Pimecrolimus 1%
      cream, or its vehicle, were applied twice daily for 6 weeks to each side of the
      mouth with a 2*2 inch gauze pad folded in half and placed directly on the erosive
      lesion. MAIN OUTCOME MEASURES: Efficacy was based on clinical evaluation of
      Investigator's Global Assessment (IGA) of the overall severity of the disease,
      erythema, measurement of the size of any target erosion in millimetres, and
      assessment of spontaneous pain. Blood levels of pimecrolimus were monitored in
      all subjects on day 0 and repeated on day 7. RESULTS: Pimecrolimus 1% cream was
      superior to vehicle cream in reducing mean IGA, pain, and erosion size. For the
      vehicle group that entered the open-label phase, pimecrolimus 1% cream improved
      the mean IGA, pain, erosion size, and erythema. Pimecrolimus levels were detected
      in nine out of 10 of the pimecrolimus-treated subjects. These levels were
      consistently low. The pimecrolimus cream was well-tolerated. No clinically
      relevant, drug-related adverse events were reported. CONCLUSION: Pimecrolimus 1%
      cream was superior to vehicle in reducing pain, erythema, decreasing erosion
      size, and improving overall severity of disease when compared with vehicle
      treatment.

PMID- 21175874
TI  - Usefulness of TrichoScan professional in the evaluation of hair loss in females.
      Report of 180 cases.
AB  - BACKGROUND: TrichoScan Professional is a computerized program used for digital
      measurement of hair growth and hair loss. The aim of our study was to undertake
      an evaluation with TrichoScan Professional of female patients consulting at our
      hospitals for hair loss. The purpose of our study was to determine whether
      TrichoScan was able to identify differences in hair parameters that would
      correlate with the pattern of alopecia or according to the age of the patients
      evaluated. MATERIAL AND METHODS: One hundred-eighty women that consulted
      consecutively for loss of hair were included. Patients were aged between 8 and 85
      years (mean age 36 years). Data including age, the number of hairs, hair density
      per square centimetre, anagen and telogen percentage and percentage of terminal
      and miniaturized hair were analysed. RESULTS: Results observed with TrichoScan
      were as below: number of hairs (mean 154.9; range 34-316). Hair density per
      square centimetre (mean 239; range 52-486). Hair in anagen phase (mean 62.4%;
      range 9-93%). Hair in telogen phase (mean 37.4%; range 7-91%). Terminal hair
      (mean 95.2%; range 82-100%). Vellus hair (mean 4.7%; range 0-17%). Pearson's
      correlation test was used to measure the strength of the association of age with
      the rest of parameters. The statistical analysis showed a significant correlation
      between age and both the number of hairs and the hair density per square
      centimetre. However, no significant correlation between age and rest of the
      parameters was observed. CONCLUSIONS: TrichoScan Professional may help to
      quantify hair density and in our sample, this was the only parameter showing a
      significant decrease according to age in various types of alopecia affecting the
      females.

PMID- 21175875
TI  - Prevalence of oral manifestations in 203 patients with psoriasis.

PMID- 21175876
TI  - Prognostic value of galectin-3 in primary cutaneous melanoma.
AB  - BACKGROUND: Galectin-3, one of the beta-galactoside-binding lectins, has been
      suggested as a marker of disease progression in melanoma patients because of its
      overexpression observed in recent studies. However, prognostic value of galectin
      3 in primary cutaneous melanoma (PCM) has not been clearly defined. OBJECTIVES:
      The aim of the study was to analyse whether the intensity of galectin-3
      expression can predict survival in patients with PMC. METHODS: Galectin-3
      expression was evaluated using immunohistochemistry in 104 PCM samples, including
      71 (68.2%) superficial spreading (SSM) and 33 (31.8%) nodular melanomas (NM).
      RESULTS: Significant difference of galectin-3 expression between SSM and NM was
      determined (P < 0.001). Increased galectin-3 expression was positively correlated
      with tumour thickness (P < 0.001), Clark (P < 0.001) and Breslow (P < 0.001)
      stage, mitotic rate (P < 0.001), presence of tumour ulceration (P < 0.001),
      lymphatic invasion (P = 0.018), positive sentinel lymph node (P < 0.022) and
      distant metastases (P < 0.001). Kaplan-Meier analysis showed an association
      between increased galectin-3 expression and reduced recurrence-free survival
      (RFS) (P = 0.001) and reduced disease-specific survival (DSS) (P = 0.015). In Cox
      proportional hazards regression analysis, significant predictors of reduced RFS
      were positive sentinel lymph node (P = 0.025) and lymphovascular invasion (P =
      0.021), whereas predictors of DSS were tumour thickness (P = 0.012),
      lymphovascular invasion (P = 0.047), Clark stage (P = 0.029) and location of
      tumour on upper extremities (P = 0.024). CONCLUSIONS: Our results support the
      potential role of galectin-3 in PCM development, progression and metastasis.
      Moreover, galectin-3 could serve as an additional prognostic marker that might
      help in further stratifying the risk of disease progression and metastasis in
      patients with PMC.

PMID- 21175877
TI  - Physical urticaria: prevalence, type and natural course in a tropical country.
AB  - BACKGROUND: Physical urticarias (PU) are an urticarial response to different
      specific physical stimuli. PU can occur concurrently with chronic spontaneous
      urticaria or another type of PU. OBJECTIVE: We aimed to study the prevalence,
      type, clinical data and natural course of each type of PU and other inducible
      urticarias and also the prognostic factors for remission of patients visiting a
      tertiary referral hospital. METHOD: We performed a retrospective study of 1200
      chronic urticaria patients who visited our Urticaria Clinic during a period of 5
      years. RESULTS: Of the 1200 chronic urticaria patients, 86 (7.2%) were diagnosed
      as PU and other inducible urticarias. The most common type of PU was symptomatic
      dermographism (n = 35, 40.7%) followed by cold urticaria (n = 20, 23.3%) and
      delayed pressure urticaria (n = 11, 12.8%), respectively. Twelve patients (13.9%)
      had associated chronic spontaneous urticaria. None of the cases had multiple
      types of PU. Erythrocyte sedimentary rate elevation was the most common abnormal
      laboratory result. Nevertheless, only 4.6% declared a related infection. For each
      type, the median time after onset before 50% remission showed that cholinergic
      urticaria took the shortest course (34 months) and delayed pressure urticaria
      took the longest period (110 months). After 1 year and 5 years from the onset of
      symptoms, 13% and 50% of PU patients were free of symptoms, respectively.
      CONCLUSION: This study emphasized the variety of PU, other inducible urticarias
      and natural courses based on tertiary hospital care. PU and other inducible
      urticarias have tendency to have a longer course than chronic spontaneous
      urticaria.

PMID- 21175878
TI  - Helicobacter pylori defines local immune response through interaction with
      dendritic cells.
AB  - The bacterial pathogen Helicobacter pylori colonizes the human gastric and
      duodenal mucosa, evades clearance by the host response and is associated with
      peptic ulcer disease and an increased risk of gastric adenocarcinoma. Dendritic
      cells (DCs) are initiators of the immune response to H. pylori. The aim of the
      current study was to investigate the interaction between H. pylori with DCs. To
      determine the impact of H. pylori on the maturation and the activation of
      monocyte-derived DCs, the effect of 20 clinical H. pylori strains with different
      inflammatory backgrounds on adenocarcinoma gastric epithelial cells was
      investigated. The inflammatory background was defined according to the degree of
      lymphocyte and granulocyte infiltration and the bacterial density at the site of
      infection. DC maturation and activation varied after exposure to the different
      strains. While maturation appeared to be independent of any virulence factor
      tested, a significant increase in the average level of cytokine production was
      observed for the proinflammatory cytokines interleukin-12 (IL-12), tumour
      necrosis factor-alpha, IL-6 and IL-1beta when comparing strains with low
      inflammatory backgrounds with those of the medium or high backgrounds. In
      conclusion, the DC response towards different strains in vitro was associated
      with the clinical outcome of the individual host, suggesting a major role of this
      cell type in modulating strain-specific H. pylori infection.

PMID- 21175879
TI  - Dose-response effect of fish oil substitution in parturition feed on erythrocyte
      membrane characteristics and sow performance.
AB  - The present study aimed to investigate whether n-3 polyunsaturated fatty acids
      (PUFA) incorporate into erythrocyte membranes of peripartal sows in a dose
      responsive manner and whether the altered fatty acid profile affects the cell
      membrane characteristics. At day 109 of gestation (day 0), 51 sows were divided
      into five treatment groups. Each group received a diet with a different ratio of
      fish oil to pork lard for nine consecutive days. Blood samples were taken at day
      0 and 10 days later. The fatty acid profile of erythrocytes was determined, as
      well as the osmotic fragility and oxidative stability of erythrocytes.
      Thiobarbituric acid reactive substances (TBARS) and ferric reducing ability of
      plasma (FRAP) were determined in plasma samples. Finally, reproductive and
      performance parameters of both sows and piglets were recorded until weaning.
      Supplementation of fish oil during the peripartal period changed the fatty acid
      profile of erythrocyte membranes in a dose-responsive manner. Although the n-3
      PUFA content of erythrocyte membranes increased with increasing amounts of fish
      oil in the diet, no significant effect on erythrocyte osmotic fragility could be
      recorded. In contrast, oxidative stability of erythrocytes decreased linearly
      with increasing amounts of fish oil in the diet. Similarly, both TBARS and FRAP
      linearly increased with increasing percentages of fish oil in the diet. Neither
      piglet nor sow performance was influenced by dietary treatments, except for a
      decrease of both piglet survival and weaning weight with increasing quantities of
      fish oil supplemented. It is concluded that changes in dietary lipid sources can
      affect the membrane's fatty acid profile within days, and mainly influences
      oxidative stability of the cells.

PMID- 21175880
TI  - Repeated exposure to morphine alters surface expression of AMPA receptors in the
      rat medial prefrontal cortex.
AB  - Behavioral sensitization describes the intensification of motor activity that
      results from repeated exposure to drugs of misuse, and the underlying neuronal
      adaptations are hypothesized to model aspects of the brain changes that occur in
      humans misusing such drugs. The alpha-amino-3-hydroxyl-5-methyl-4-isoxazole
      propionate (AMPA) receptor is an ionotropic glutamate receptor involved in the
      neuroplasticity that accompanies acute and repeated drug administration. Changing
      surface expression is one means to regulate AMPA receptor function, and the
      present study tested the hypothesis that behavioral sensitization to the MU
      opioid receptor agonist morphine is accompanied by changes in the subcellular
      distribution of AMPA receptors in limbic brain regions. To test this hypothesis,
      we used a protein cross-linking assay to assess cell surface and intracellular
      levels of GluA1 and GluA2 subunits in the nucleus accumbens, medial prefrontal
      cortex and ventral pallidum. Repeated morphine treatment decreased surface
      expression of GluA1 in the medial prefrontal cortex without affecting levels of
      GluA2. In contrast, surface levels of GluA1 or GluA2 were unchanged in the
      nucleus accumbens and ventral pallidum, demonstrating that although AMPA
      receptors in accumbal and pallidal regions are critical mediators of behaviors
      induced by repeated opiate exposure, these effects are not accompanied by changes
      in surface expression. The findings reveal that the involvement of AMPA receptor
      trafficking in opiate-induced behavioral sensitization is relegated to selective
      regions and that AMPA receptors in the medial prefrontal cortex may be
      particularly sensitive to these actions.

PMID- 21175881
TI  - Functional MRI evidence for the importance of visual short-term memory in
      logographic reading.
AB  - Logographic symbols are visually complex, and thus children's abilities for
      visual short-term memory (VSTM) predict their reading competence in logographic
      systems. In the present study, we investigated the importance of VSTM in
      logographic reading in adults, both behaviorally and by means of fMRI. Outside
      the scanner, VSTM predicted logographic Kanji reading in native Japanese adults
      (n=45), a finding consistent with previous observations in Japanese children. In
      the scanner, participants (n=15) were asked to perform a visual one-back task.
      For this fMRI experiment, we took advantage of the unique linguistic
      characteristic of the Japanese writing system, whereby syllabic Kana and
      logographic Kanji can share the same sound and meaning, but differ only in the
      complexity of their visual features. Kanji elicited greater activation than Kana
      in the cerebellum and two regions associated with VSTM, the lateral occipital
      complex and the superior intraparietal sulcus, bilaterally. The same regions
      elicited the highest activation during the control condition (an unfamiliar,
      unpronounceable script to the participants), presumably due to the increased VSTM
      demands for processing the control script. In addition, individual differences in
      VSTM performance (outside the scanner) significantly predicted blood oxygen level
      dependent signal changes in the identified VSTM regions, during the Kanji and
      control conditions, but not during the Kana condition. VSTM appears to play an
      important role in reading logographic words, even in skilled adults, as evidenced
      at the behavioral and neural level, most likely due to the increased VSTM/visual
      attention demands necessary for processing complex visual features inherent in
      logographic symbols.

PMID- 21175882
TI  - Mislocalization of near-threshold tactile stimuli in humans: a central or
      peripheral phenomenon?
AB  - Principles of brain function can be disclosed by studying their limits during
      performance. Tactile stimuli with near-threshold intensities have been used to
      assess features of somatosensory processing. When stimulating fingers of one hand
      using near-threshold intensities, localization errors are observed that deviate
      significantly from responses obtained by guessing - incorrectly located stimuli
      are attributed more often to fingers neighbouring the stimulated one than to more
      distant fingers. Two hypotheses to explain the findings are proposed. The
      'central hypothesis' posits that the degree of overlap of cortical tactile
      representations depends on stimulus intensity, with representations less
      separated for near-threshold stimuli than for suprathreshold stimuli. The
      'peripheral hypothesis' assumes that systematic mislocalizations are due to
      activation of different sets of skin receptors with specific thresholds. The
      present experiments were designed to decide between the two hypotheses. Taking
      advantage of the frequency tuning of somatosensory receptors, their contribution
      to systematic misclocalizations was studied. In the first experiment,
      mislocalization profiles were investigated using vibratory stimuli with
      frequencies of 10, 20 and 100 Hz. Unambiguous mislocalization effects were only
      obtained for the 10-Hz stimulation, precluding the involvement of Pacinian
      corpuscles in systematic mislocalization. In the second experiment, Pacinian
      corpuscles were functionally eliminated by applying a constant 100-Hz vibratory
      masking stimulus together with near-threshold pulses. Despite masking, systematic
      mislocation patterns were observed rendering the involvement of Pacinian
      corpuscles unlikely. The results of both experiments are in favor of the 'central
      hypothesis' assuming that the extent of overlap in somatosensory representations
      is modulated by stimulus intensity.

PMID- 21175883
TI  - Delay activity in avian prefrontal cortex--sample code or reward code?
AB  - In the current study, we examined whether delay activity in the avian equivalent
      of the prefrontal cortex (PFC) represents a neural correlate of a to-be
      remembered sample stimulus or an upcoming reward. Birds were trained on a
      directed forgetting paradigm in which sample stimuli (red and white) were either
      followed by a cue to remember (high-frequency tone) or a cue to forget (low
      frequency tone). The task also incorporated a differential outcomes procedure in
      which a correct response on the memory test following a red (remember) sample was
      rewarded with food, but correct responses on the memory test following the white
      (remember) sample were not. If delay activity represents a sample code, then it
      should be seen on both red-remember and white-remember trials. On the other hand,
      if delay activity represents a reward code, then delay activity should be seen
      only on red-remember trials, but not white-remember trials. Our findings suggest
      that activity in the avian PFC represents the outcome associated with each sample
      (reward or no reward) rather than memory for the sample itself.

PMID- 21175884
TI  - Effect of sensory stimulation in rat barrel cortex, dorsolateral striatum and on
      corticostriatal functional connectivity.
AB  - The striatum integrates sensory information to enable action selection and
      behavioural reinforcement. In the rat, a large topographical projection from the
      rat barrel cortex to widely distributed areas of the striatum is assumed to be an
      important structural component supporting these processes. The striatal sensory
      response is, however, not comprehensively understood at a network level. We used
      a 10-Hz, 100-ms air puff, allowing undamped movement of multiple whiskers, to
      look at functional connectivity in contralateral cortex and striatum in response
      to sensory stimulation. Simultaneous recordings of cortical and striatal local
      field potentials (LFPs) were made under isoflurane anaesthesia in 15 male Brown
      Norway rats. Four electrodes were placed in the barrel cortex while the
      dorsolateral striatum was mapped with a 500-MUm resolution, resulting in a
      maximum of 315 recording positions per animal. Significant event-related
      responses were unevenly distributed throughout the striatum in 34.8% of positions
      recorded within this area. Only 10.3% of recorded positions displayed significant
      total power increases in the LFPs during the stimulation period at the stimulus
      frequency. This suggests that the responses seen in the LFPs are due to phase
      rearrangement rather than an amplitude increase in the signal. Analysis of
      corticostriatal imaginary coherence revealed stimulus-induced changes in the
      functional connectivity of 12% of corticostriatal pairs, the sensory response of
      sparsely distributed neuronal ensembles within the dorsolateral striatum is
      reflected in the phase relationship between the cortical and striatal local
      fields.

PMID- 21175885
TI  - CalS7 encodes a callose synthase responsible for callose deposition in the
      phloem.
AB  - It has been known for more than a century that sieve plates in the phloem in
      plants contain callose, a beta-1,3-glucan. However, the genes responsible for
      callose deposition in this subcellular location have not been identified. In this
      paper we examine callose deposition patterns in T-DNA insertion mutants (cs7) of
      the Callose Synthase 7 (CalS7) gene. We demonstrated here that the CalS7 gene is
      expressed specifically in the phloem of vascular tissues. Callose deposition in
      the phloem, especially in the sieve elements, was greatly reduced in cs7 mutants.
      Ultrastructural analysis of developing sieve elements revealed that callose
      failed to accumulate in the plasmodesmata of incipient sieve plates at the early
      perforation stage of phloem development, resulting in the formation of sieve
      plates with fewer pores. In wild-type Arabidopsis plants, callose is present as a
      constituent polysaccharide in the phloem of the stem, and its accumulation can
      also be induced by wounding. Callose accumulation in both conditions was
      eliminated in mature sieve plates of cs7 mutants. These results demonstrate that
      CalS7 is a phloem-specific callose synthase gene, and is responsible for callose
      deposition in developing sieve elements during phloem formation and in mature
      phloem induced by wounding. The mutant plants exhibited moderate reduction in
      seedling height and produced aberrant pollen grains and short siliques with
      aborted embryos, suggesting that CalS7 also plays a role in plant growth and
      reproduction.

PMID- 21175886
TI  - The chloroplastic 2-oxoglutarate/malate transporter has dual function as the
      malate valve and in carbon/nitrogen metabolism.
AB  - Transport of dicarboxylates across the chloroplast envelope plays an important
      role in transferring carbon skeletons to the nitrogen assimilation pathway and
      exporting reducing equivalent to the cytosol to prevent photo-inhibition (the
      malate valve). It was previously shown that the Arabidopsis plastidic 2
      oxoglutarate/malate transporter (AtpOMT1) and the general dicarboxylate
      transporter (AtpDCT1) play crucial roles at the interface between carbon and
      nitrogen metabolism. However, based on the in vitro transport properties of the
      recombinant transporters, it was hypothesized that AtpOMT1 might play a dual
      role, also functioning as an oxaloacetate/malate transporter, which is a crucial
      but currently unidentified component of the chloroplast malate valve. Here, we
      test this hypothesis using Arabidopsis T-DNA insertional mutants of AtpOMT1.
      Transport studies revealed a dramatically reduced rate of oxaloacetate uptake
      into chloroplasts isolated from the knockout plant. CO(2) -dependent O(2)
      evolution assays showed that cytosolic oxaloacetate is efficiently transported
      into chloroplasts mainly by AtpOMT1, and supported the absence of additional
      oxaloacetate transporters. These findings strongly indicate that the high
      affinity oxaloacetate transporter in Arabidopsis chloroplasts is AtpOMT1.
      Further, the knockout plants showed enhanced photo-inhibition under high light
      due to greater accumulation of reducing equivalents in the stroma, indicating
      malfunction of the malate valve in the knockout plants. The knockout mutant
      showed a phenotype consistent with reductions in 2-oxoglutarate transport,
      glutamine synthetase/glutamate synthase activity, subsequent amino acid
      biosynthesis and photorespiration. Our results demonstrate that AtpOMT1 acts bi
      functionally as an oxaloacetate/malate transporter in the malate valve and as a 2
      oxoglutarate/malate transporter mediating carbon/nitrogen metabolism.

PMID- 21175887
TI  - Two putatively homoeologous wheat genes mediate recognition of SnTox3 to confer
      effector-triggered susceptibility to Stagonospora nodorum.
AB  - The pathogen Stagonospora nodorum produces multiple effectors, also known as host
      selective toxins (HSTs), that interact with corresponding host sensitivity genes
      in an inverse gene-for-gene manner to cause the disease Stagonospora nodorum
      blotch (SNB) in wheat. In this study, a sensitivity gene was identified in
      Aegilops tauschii, the diploid D-genome donor of common wheat. The gene was
      mapped to the short arm of chromosome 5D and mediated recognition of the effector
      SnTox3, which was previously shown to be recognized by the wheat gene Snn3 on
      chromosome arm 5BS. Comparative mapping suggested that Snn3 and the gene on 5DS
      are probably homoeologous and derived from a common ancestor. Therefore, we
      propose to designate these genes as Snn3-B1 and Snn3-D1, respectively. Compatible
      Snn3-D1-SnTox3 interactions resulted in more severe necrosis in both effector
      infiltration and spore inoculation experiments than compatible Snn3-B1-SnTox3
      interactions, indicating that Snn3-B1 and Snn3-D1 may have different affinities
      in SnTox3 recognition or signal transduction. Wheat bin-mapped expressed sequence
      tags and good levels of collinearity among the wheat Snn3 regions, rice (Oryza
      sativa), and Brachypodium distachyon were exploited for saturation and fine
      mapping of the Snn3-D1 locus. Markers delineating the Snn3-D1 locus to a 1.4 cM
      interval will be useful for initiating positional cloning. Further
      characterization of how these homoeologous genes mediate recognition of the same
      pathogen effector should enhance understanding of host manipulation by
      necrotrophic pathogens in causing disease.

PMID- 21175888
TI  - Nodulation factor receptor kinase 1alpha controls nodule organ number in soybean
      (Glycine max L. Merr).
AB  - Two allelic non-nodulating mutants, nod49 and rj1, were characterized using map
      based cloning and candidate gene approaches, and genetic complementation. From
      our results we propose two highly related lipo-oligochitin LysM-type receptor
      kinase genes (GmNFR1alpha and GmNFR1beta) as putative Nod factor receptor
      components in soybean. Both mutants contained frameshift mutations in GmNFR1alpha
      that would yield protein truncations. Both mutants contained a seemingly
      functional GmNFR1beta homeologue, characterized by a 374-bp deletion in intron 6
      and 20-100 times lower transcript levels than GmNFR1alpha, yet both mutants were
      unable to form nodules. Mutations in GmNFR1beta within other genotypes had no
      defects in nodulation, showing that GmNFR1beta was redundant. Transgenic
      overexpression of GmNFR1alpha, but not of GmNFR1beta, increased nodule number per
      plant, plant nitrogen content and the ability to form nodules with restrictive,
      ultra-low Bradyrhizobium japonicum titres in transgenic roots of both nod49 and
      rj1. GmNFR1alpha overexpressing roots also formed nodules in nodulation
      restrictive acid soil (pH 4.7). Our results show that: (i) NFR1alpha expression
      controls nodule number in soybean, and (ii) acid soil tolerance for nodulation
      and suppression of nodulation deficiency at low titre can be achieved by
      overexpression of GmNFR1alpha.

PMID- 21175889
TI  - Involvement of Elongin C in the spread of repressive histone modifications.
AB  - In our previous work, we induced RNA interference (RNAi) against the
      spectinomycin resistance-conferring aadA transgene by transcribing a long
      inverted repeat in Chlamydomonas reinhardtii. However, after long-term culture,
      the level of transcripts of the inverted repeat was markedly decreased. In this
      study, we performed random insertional mutagenesis of the RNAi strain to identify
      the genes that contribute to the transcriptional silencing of the silencer
      construct. We succeeded in isolating several mutants showing derepression of
      transcription of the inverted repeat. One of these tag mutant strains, 148-10H,
      had a deletion of the Elongin C gene (ELC), which is a component of some E3
      ubiquitin ligase complexes. In the mutant, the level of monomethyl histone H3 on
      lysine 9 (H3K9me1) was reduced to less than half of the parental strain, and a
      large portion of deacetylated H3 marks were removed from the promoter region of
      the silencer construct, while these repressive histone modifications and levels
      of methyl-CpG levels were retained in the inverted repeat region. The most
      probable interpretation of the above-mentioned phenomenon is that ELC is
      essential for stepwise extension of heterochromatin formation that is nucleated
      in the inverted region over the promoter region.

PMID- 21175890
TI  - AGAMOUS-LIKE 6 is a floral promoter that negatively regulates the FLC/MAF clade
      genes and positively regulates FT in Arabidopsis.
AB  - MADS-box genes encode a family of transcription factors that regulate diverse
      developmental programs in plants. The present work shows the regulation of
      flowering time by AGL6 through control of the transcription of both a subset of
      the FLOWERING LOCUS C (FLC) family genes and FT, two key regulators of flowering
      time. The agl6-1D mutant, in which AGL6 was activated by the 35S enhancer, showed
      an early flowering phenotype under both LD and SD conditions. Its early flowering
      was additively accelerated by CONSTANS (CO) overexpression. The agl6-1D mutation
      strongly suppressed the late flowering of fve-4 and fca-9 mutants. Endogenous
      AGL6 transcript accumulation was photoperiod-independent and the AGL6:GFP protein
      was preferentially localized in the nucleus. In agl6-1D plants, the expression of
      FLC, MADS AFFECTING FLOWERING (MAF) 4, and MAF5 was downregulated. Interestingly,
      late flowering of a functional FRIGIDA (FRI) FLC allele was dramatically
      suppressed by the agl6-1D mutation. AGL6 activation in the flc-3 background
      further enhanced FT expression, suggesting that AGL6 also regulates FT expression
      independently of FLC mRNA level. A near RNA-null ft-10 mutation completely
      suppressed early flowering of the agl6-1D plants, suggesting that FT is a major
      downstream output of AGL6. Transgenic plants overexpressing an artificial
      microRNA targeting AGL6 showed a late-flowering phenotype. In these plants, FT
      expression was downregulated, whereas FLC expression was upregulated. The present
      results suggest that AGL6 acts as a floral promoter with a dual role, the
      inhibition of the transcription of the FLC/MAF genes and the promotion of FT
      expression in Arabidopsis.

PMID- 21175891
TI  - Temporal and spatial regulation of DROOPING LEAF gene expression that promotes
      midrib formation in rice.
AB  - Genes involved in the differentiation and development of tissues and organs are
      temporally and spatially regulated in plant development. The DROOPING LEAF (DL)
      gene, a member of the YABBY gene family, promotes midrib formation in the leaf
      and carpel specification in the flower. Consistent with these functions, DL is
      initially expressed in the central region of the leaf primordia (presumptive
      midrib) and in the presumptive carpel primordia in the meristem. To understand
      the regulatory mechanism underlying DL expression, we tried to identify cis
      regulatory regions required for temporal and spatial expression of this gene. We
      found that the cis region responsible for the presumptive midrib-specific
      expression in the leaf primordia is located in intron 2. Next, we confined the
      region to a sequence of about 200bp, which corresponds to a conserved non-coding
      sequence (CNS) identified by phylogenetic footprinting. In addition, a sequence
      termed DG1, incorporating a 5' upstream region of about 7.4kb, and introns 1 and
      2, was shown to be sufficient to induce DL in the presumptive midrib, and to
      suppress it in other regions in the leaf primordia. By contrast, the regulatory
      region required for carpel-specific expression was not included in the DG1
      sequence. We modified Oryza sativa (rice) plant architecture by expressing an
      activated version of DL (DL-VP16) in a precise manner using the DG1 sequence: the
      resulting transgenic plant produced a midrib in the distal region of the leaf
      blade, where there is no midrib in wild type, and formed more upright leaves
      compared with the wild type.

PMID- 21175892
TI  - CYP99A3: functional identification of a diterpene oxidase from the momilactone
      biosynthetic gene cluster in rice.
AB  - Rice (Oryza sativa) produces momilactone diterpenoids as both phytoalexins and
      allelochemicals. Strikingly, the rice genome contains a biosynthetic gene cluster
      for momilactone production, located on rice chromosome 4, which contains two
      cytochrome P450 (CYP) mono-oxygenases, CYP99A2 and CYP99A3, with undefined roles;
      although it has been previously shown that RNA interference double knock-down of
      this pair of closely related CYPs reduced momilactone accumulation. Here we
      attempted biochemical characterization of CYP99A2 and CYP99A3, which was
      ultimately achieved by complete gene recoding, enabling functional recombinant
      expression in bacteria. With these synthetic gene constructs it was possible to
      demonstrate that while CYP99A2 does not exhibit significant activity with
      diterpene substrates, CYP99A3 catalyzes consecutive oxidations of the C19 methyl
      group of the momilactone precursor syn-pimara-7,15-diene to form, sequentially,
      syn-pimaradien-19-ol, syn-pimaradien-19-al, and syn-pimaradien-19-oic acid. These
      are presumably intermediates in momilactone biosynthesis, as a C19 carboxylic
      acid moiety is required for formation of the core 19,6-gamma-lactone ring
      structure. We further were able to detect syn-pimaradien-19-oic acid in rice
      plants, which indicates physiological relevance for the observed activity of
      CYP99A3. In addition, we found that CYP99A3 also oxidized syn-stemod-13(17)-ene
      at C19 to produce, sequentially, syn-stemoden-19-ol, syn-stemoden-19-al, and syn
      stemoden-19-oic acid, albeit with lower catalytic efficiency than with syn
      pimaradiene. Although the CYP99A3 syn-stemodene-derived products were not
      detected in planta, these results nevertheless provide a hint at the currently
      unknown metabolic fate of this diterpene in rice. Regardless of any wider role,
      our results strongly indicate that CYP99A3 acts as a multifunctional diterpene
      oxidase in momilactone biosynthesis.

PMID- 21175893
TI  - Control of sulfur partitioning between primary and secondary metabolism.
AB  - Sulfur is an essential nutrient for all organisms. Plants take up most sulfur as
      inorganic sulfate, reduce it and incorporate it into cysteine during primary
      sulfate assimilation. However, some of the sulfate is partitioned into the
      secondary metabolism to synthesize a variety of sulfated compounds. The two
      pathways of sulfate utilization branch after activation of sulfate to adenosine
      5'-phosphosulfate (APS). Recently we showed that the enzyme APS kinase limits the
      availability of activated sulfate for the synthesis of sulfated secondary
      compounds in Arabidopsis. To further dissect the control of sulfur partitioning
      between the primary and secondary metabolism, we analysed plants in which
      activities of enzymes that use APS as a substrate were increased or reduced.
      Reduction in APS kinase activity led to reduced levels of glucosinolates as a
      major class of sulfated secondary metabolites and an increased concentration of
      thiols, products of primary reduction. However, over-expression of this gene does
      not affect the levels of glucosinolates. Over-expression of APS reductase had no
      effect on glucosinolate levels but did increase thiol levels, but neither
      glucosinolate nor thiol levels were affected in mutants lacking the APR2 isoform
      of this enzyme. Measuring the flux through sulfate assimilation using [(35)
      S]sulfate confirmed the larger flow of sulfur to primary assimilation when APS
      kinase activity was reduced. Thus, at least in Arabidopsis, the interplay between
      APS reductase and APS kinase is important for sulfur partitioning between the
      primary and secondary metabolism.

PMID- 21175894
TI  - Identification and characterisation of F3GT1 and F3GGT1, two glycosyltransferases
      responsible for anthocyanin biosynthesis in red-fleshed kiwifruit (Actinidia
      chinensis).
AB  - Much of the diversity of anthocyanins is due to the action of
      glycosyltransferases, which add sugar moieties to anthocyanidins. We identified
      two glycosyltransferases, F3GT1 and F3GGT1, from red-fleshed kiwifruit (Actinidia
      chinensis) that perform sequential glycosylation steps. Red-fleshed genotypes of
      kiwifruit accumulate anthocyanins mainly in the form of cyanidin 3-O-xylo
      galactoside. Genes in the anthocyanin and flavonoid biosynthetic pathway were
      identified and shown to be expressed in fruit tissue. However, only the
      expression of the glycosyltransferase F3GT1 was correlated with anthocyanin
      accumulation in red tissues. Recombinant enzyme assays in vitro and in vivo RNA
      interference (RNAi) demonstrated the role of F3GT1 in the production of cyanidin
      3-O-galactoside. F3GGT1 was shown to further glycosylate the sugar moiety of the
      anthocyanins. This second glycosylation can affect the solubility and stability
      of the pigments and modify their colour. We show that recombinant F3GGT1 can
      catalyse the addition of UDP-xylose to cyanidin 3-galactoside. While F3GGT1 is
      responsible for the end-product of the pathway, F3GT1 is likely to be the key
      enzyme regulating the accumulation of anthocyanin in red-fleshed kiwifruit
      varieties.

PMID- 21175895
TI  - Protein arginine methylation modulates light-harvesting antenna translation in
      Chlamydomonas reinhardtii.
AB  - Methylation of protein arginines represents an important post-translational
      modification mechanism, which has so far primarily been characterized in
      mammalian cells. In this work, we successfully identified and characterized
      arginine methylation as a crucial type of post-translational modification in the
      activity regulation of the cytosolic translation repressor protein NAB1 in the
      plant model organism Chlamydomonas reinhardtii. NAB1 represses the cytosolic
      translation of light-harvesting protein encoding mRNAs by sequestration into
      translationally silent messenger ribonucleoprotein complexes (mRNPs). Protein
      arginine methylation of NAB1 could be demonstrated by PRMT1 catalyzed methylation
      of recombinant NAB1 in vitro, and by immunodetection of methylated NAB1 arginines
      in vivo. Mass spectrometric analyses of NAB1 purified from C. reinhardtii
      revealed the asymmetric dimethylation of Arg90 and Arg92 within GAR motif I.
      Inhibition of arginine methylation by either adenosine-2'-3'-dialdehyde (AdOx) or
      7,7'-carbonylbis(azanediyl)bis(4-hydroxynaphthalene-2-sulfonic acid) sodium salt
      hydrate (AMI-1) caused a dark-green phenotype characterized by the increased
      accumulation of light-harvesting complex proteins, and indicating a reduced
      translation repressor activity of NAB1. The extent of NAB1 arginine methylation
      depends on the growth conditions, with phototrophic growth causing a high
      methylation state and heterotrophic growth resulting in lowered methylation of
      the protein. In addition, we could show that NAB1 activity regulation by arginine
      methylation operates independently from cysteine-based redox control, which has
      previously been shown to control the activity of NAB1.

PMID- 21175896
TI  - Dynamic changes of transcript profiles after fertilization are associated with de
      novo transcription and maternal elimination in tobacco zygote, and mark the onset
      of the maternal-to-zygotic transition.
AB  - The maternal-to-zygotic transition (MZT) is characterized by the turnover of
      zygote development from maternal to zygotic control, and has been extensively
      studied in animals. A majority of studies have suggested that early embryogenesis
      is maternally controlled and that the zygotic genome remains transcriptionally
      inactive prior to the MZT. However, little is known about the MZT in higher
      plants, and its timing and impact remain uncharacterized. Here, we constructed
      cDNA libraries from tobacco (Nicotiana tabacum) egg cells, zygotes and two-celled
      embryos for gene expression profiling analysis, followed by RT-PCR confirmation.
      These analyses, together with experiments using zygote microculture coupled with
      transcription inhibition, revealed that a marked change in transcript profiles
      occurs approximately 50 h after fertilization, and that the MZT is initiated
      prior to zygotic division in tobacco. Although maternal transcripts deposited in
      egg cells support several early developmental processes, they appear to be
      insufficient for zygotic polar growth and subsequent cell divisions. Thus, we
      propose that de novo transcripts are probably required to trigger embryogenesis
      in later zygotes in tobacco.

PMID- 21175897
TI  - Temperature controls nuclear import of Tam3 transposase in Antirrhinum.
AB  - It has been proposed that environmental stimuli can activate transposable
      elements (TEs), whereas few substantial mechanisms have been shown so far. The
      class-II element Tam3 from Antirrhinum majus exhibits a unique property of low
      temperature-dependent transposition (LTDT). LTDT has proved invaluable in
      developing the gene isolation technologies that have underpinned much of modern
      plant developmental biology. Here, we reveal that LTDT involves differential
      subcellular localization of the Tam3 transposase (TPase) in cells grown at low
      (15 degrees C) and high (25 degrees C) temperatures. The mechanism is associated
      with the nuclear import of Tam3 TPase in Antirrhinum cells. At high temperature,
      the nuclear import of Tam3 TPase is severely restricted in Antirrhinum cells,
      whereas at low temperature, the nuclear localization of Tam3 TPase is observed in
      about 20% of the cells. However, in tobacco BY-2 and Allium cepa (onion) cells,
      Tam3 TPase is transported into most nuclei. In addition to three nuclear
      localization signals (NLSs), the Tam3 TPase is equipped with a nuclear
      localization inhibitory domain (NLID), which functions to abolish nuclear import
      of the TPase at high temperature in Antirrhinum. NLID in Tam3 TPase is considered
      to interact with Antirrhinum-specific factor(s). The host-specific regulation of
      the nuclear localization of transposase represents a new repertoire controlling
      class-II TEs.

PMID- 21175898
TI  - Virus-mediated efficient induction of epigenetic modifications of endogenous
      genes with phenotypic changes in plants.
AB  - Gene silencing through transcriptional repression can be induced by targeting
      double-stranded RNA (dsRNA) to a gene promoter. It has been reported that a
      transgene was silenced by targeting dsRNA to the promoter, and the silenced state
      was inherited to the progeny plant even after removal of the silencing inducer
      from cells. In contrast, no plant has been produced that harbors silenced
      endogenous gene after removal of promoter-targeting dsRNA. Here, we show that
      heritable gene silencing can be induced by targeting dsRNA to the endogenous gene
      promoters in petunia and tomato plants, using the Cucumber mosaic virus (CMV)
      based vector. We found that efficient silencing of endogenous genes depends on
      the function of the 2b protein encoded in the vector virus, which has the ability
      to facilitate epigenetic modifications through the transport of short interfering
      RNA to nucleus. Bisulfite sequencing analyses on the targeted promoter in the
      virus-infected and its progeny plants revealed that cytosine methylation was
      found not only at CG or CNG but also at CNN sites. The observed inheritance of
      asymmetric DNA methylation is quite unique, suggesting that plants have a
      mechanism to maintain even asymmetric methylation. This CMV-based gene silencing
      system provides a useful tool to artificially modify DNA methylation in plant
      genomes and elucidate the mechanism for epigenetic controls.

PMID- 21175899
TI  - Hyperphagia and leptin resistance in tissue inhibitor of metalloproteinase-2
      deficient mice.
AB  - Obesity is a complex genetic and behavioural disorder arising from the improper
      integration of peripheral signals at central autonomic centres. For the
      hypothalamus to respond to dynamic physiological alterations, it must retain a
      degree of plasticity throughout life. Evidence is mounting that an intricate
      balance between matrix metalloproteinase (MMP)-mediated extracellular matrix
      proteolysis and tissue inhibitor of metalloproteinase (TIMP)-mediated proteolysis
      inhibition contributes to tissue remodelling. However, few studies have examined
      the role of MMPs/TIMPs in hypothalamic remodelling and energy homeostasis. To
      determine the contribution of TIMP-2 to the hypothalamic regulation of feeding,
      body mass and food consumption were monitored in TIMP-2 knockout (KO) mice fed a
      standard chow or high-fat diet (HFD). TIMP-2 KO mice of both sexes gained more
      weight than wild-type (WT) mice, even when fed the chow diet. Before the onset of
      obesity, TIMP-2 KO mice were hyperphagic, without increased orexigenic or
      decreased anorexigenic neuropeptide expression, but leptin resistant (i.e.
      reduced leptin-induced anorexigenic response and signal transducer and activator
      of transcription 3 activation). HFD exacerbated weight gain and hyperleptinaemia.
      In addition, proteolysis was increased in the arcuate nucleus of TIMP-2 KO mice.
      These data suggest a role for TIMP-2 in hypothalamic control of feeding and
      energy homeostasis.

PMID- 21175900
TI  - Asymmetric dimethylarginine as an independent risk marker for mortality in
      ambulatory patients with peripheral arterial disease.
AB  - BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of
      nitric oxide (NO) synthesis causing endothelial dysfunction, an early sign of
      atherogenesis. Symmetric dimethylarginine (SDMA) does not inhibit NO synthases.
      Peripheral arterial disease (PAD) is a systemic indication of atherosclerosis.
      METHODS: We assessed the associations between both ADMA and SDMA blood levels and
      major cardiovascular and cerebrovascular events or death from any cause within a
      5-year follow-up in the multicentre getABI trial. From a cohort of 6821 primary
      care patients, aged >=65 years, all 1260 patients with prevalent PAD were
      compared with a random sample of 1187 non-PAD controls. A total of 11,544 patient
      years were documented. Multivariate risks were calculated by Cox proportional
      hazard models, adjusting for PAD, renal dysfunction and other important
      cardiovascular risk factors. RESULTS: We documented 390 deaths, 296
      cardiovascular events and 98 cerebrovascular events. Increased ADMA levels in the
      4th quartile were significantly associated with total mortality [hazard ratio
      (HR) 1.41; 95% CI 1.14-1.74] and with cardiovascular events (HR 1.32; 95% CI 1.03
      1.69), but there was a nonsignificant association with cerebrovascular events (HR
      1.50; 95% CI 0.98-2.29). Increased SDMA was only just significantly associated
      with mortality (HR 1.27; 95% CI 1.01-1.59). In PAD patients compared with non-PAD
      controls, only mean SDMA concentration was considerably increased (0.52 MUmol L(
      1) vs. 0.48 MUmol L(-1); P < 0.001) mainly because of a highly significant
      association with impaired renal function. CONCLUSION: These data suggest that
      ADMA but not SDMA is an independent risk marker for death from any cause or from
      cardiovascular events. The association between SDMA and mortality is in part
      explained by a close link between SDMA and renal function.

PMID- 21175901
TI  - Quality of diet is important for the prevention of cardiovascular disease.

PMID- 21175902
TI  - Factors associated with reaching 90 years of age: a study of men born in 1913 in
      Gothenburg, Sweden.
AB  - OBJECTIVES: Increasing numbers of people reach old age. We wanted to identify
      variables of importance for reaching 90 years old and determine how the
      predictive ability of these variables might change over time. SETTING AND
      SUBJECTS: All men in the city of Gothenburg born in 1913 on dates divisible by 3,
      which is on the 3rd, 6th, 9th etc., were included in the study. Thus, 973 men
      were invited, and 855 were examined in 1963 at age 50. Further examinations were
      made at age 54, 60 and 67. Anthropometric data, lifestyle and parental factors,
      blood pressure, lung function, X-ray of heart and lungs and maximum work
      performance were recorded. The area under the receiver operating characteristic
      curve was used to analyse the predictive capacity of a variable. RESULTS: A total
      of 111 men (13%) reached 90 years of age, men who reached 90 years were more
      likely at age 50 to be nonsmokers, consume less coffee, have higher socio
      economic status and have low serum cholesterol levels than those who did not
      reach this age; however, at age 50 or 62, parents' survival was of no prognostic
      importance. Variables of greatest importance at higher ages were low blood
      pressure and measures related to good cardiorespiratory function. In
      multivariable analysis, including all examinations, being a nonsmoker, consuming
      small amounts of coffee, having high housing costs at age 50, good maximum
      working capacity and low serum cholesterol were related to a better chance of
      survival to age 90. CONCLUSIONS: Low levels of cardiovascular risk factors, high
      socio-economic status and good functional capacity, irrespective of parents'
      survival, characterize men destined to reach the age of 90.

PMID- 21175903
TI  - Smoking and the outcome of infection.
AB  - Smoking has substantial local and systemic adverse effects on the immune system,
      respiratory tract and skin and soft tissues. Smokers are at increased risk of
      invasive pneumococcal disease, pneumonia, periodontitis, surgical infections,
      tuberculosis, influenza and meningococcal disease. The results of several studies
      indicate that smokers with periodontitis or tuberculosis suffer more severe
      disease. Data on the impact of smoking on sepsis and pneumonia are controversial
      and limited, and systematic data regarding the outcome of the majority of
      infections in smokers are scarce. Abundant data indicate that children exposed to
      environmental tobacco smoke (ETS) suffer from more severe infections. However,
      information regarding the effects of ETS on the outcome of infections in adults
      is limited. Various aspects of the relation between smoking and the outcome of
      bacterial infection (e.g. potential dose-dependent effects and the interactions
      between smoking and other environmental factors that may affect the course of
      infectious diseases) remain to be established.

PMID- 21175904
TI  - Haemolytic anaemia and renal failure associated with antibodies to trimethoprim
      and sulfamethoxazole.
AB  - AIM: The aim of this study was to support a clinical diagnosis of drug-induced
      immune haemolytic anaemia (DIIHA). BACKGROUND: DIIHA is rare and has only been
      described twice with the antibiotic combination of trimethoprim (TMP) and
      sulfamethoxazole (SMX). METHODS/MATERIALS: Serologic tests for drug antibodies
      were performed using methods previously published by our laboratory. RESULTS: A
      44-year-old woman experienced body aches, chills, chest pressure, nausea and a
      rash while receiving TMP-SMX; a week later her haemoglobin was low and she was in
      renal failure. At the hospital, the direct antiglobulin test (DAT) was positive
      (C3 only) and the serum reacted with all red blood cells (RBCs) by the gel method
      only (TMP-SMX is present in the RBC diluent used for the gel method). At the Red
      Cross immunohaematology laboratory, the patient's serum was reactive in the
      presence of TMP-SMX (haemolysis and positive antiglobulin test), pure TMP
      (positive antiglobulin test using anti-IgG only) and pure SMX (haemolysis and
      positive antiglobulin test using both anti-IgG and anti-C3). The patient was
      treated with transfusions and haemodialysis and was discharged after a week in
      stable condition. CONCLUSION: We describe a patient who appeared to have
      haemolytic anaemia and renal failure associated with antibodies to both TMP and
      SMX.

PMID- 21175906
TI  - Inferring landscape effects on dispersal from genetic distances: how far can we
      go?
AB  - Functional connectivity affects demography and gene dynamics in fragmented
      populations. Besides species-specific dispersal ability, the connectivity between
      local populations is affected by the landscape elements encountered during
      dispersal. Documenting these effects is thus a central issue for the conservation
      and management of fragmented populations. In this study, we compare the power and
      accuracy of three methods (partial correlations, regressions and Approximate
      Bayesian Computations) that use genetic distances to infer the effect of
      landscape upon dispersal. We use stochastic individual-based simulations of
      fragmented populations surrounded by landscape elements that differ in their
      permeability to dispersal. The power and accuracy of all three methods are good
      when there is a strong contrast between the permeability of different landscape
      elements. The power and accuracy can be further improved by restricting analyses
      to adjacent pairs of populations. Landscape elements that strongly impede
      dispersal are the easiest to identify. However, power and accuracy decrease
      drastically when landscape complexity increases and the contrast between the
      permeability of landscape elements decreases. We provide guidelines for future
      studies and underline the needs to evaluate or develop approaches that are more
      powerful.

PMID- 21175907
TI  - The impacts of short break provision on families with a disabled child: an
      international literature review.
AB  - There are widespread assumptions about the potential impacts of short breaks on
      family carers and disabled children. This review aims to evaluate the existing
      international research evidence concerning the impacts of short breaks on
      families with a disabled child. Electronic literature searches were conducted
      using ASSIA, PsycInfo, CINAHL, and Web of Science, and requests for information
      were sent to selected email lists. Of 60 articles or reports identified for
      inclusion in the review, the vast majority of studies were cross-sectional, with
      only eight studies using quasi-experimental pre-post designs or longitudinal
      designs. Nonetheless, the consistency with which some findings have been reported
      suggests that short breaks appear to have the potential to positively impact on
      not only the well-being of carers, but also the children receiving short breaks
      and their families as a whole. Additional research is warranted in a number of
      areas. First, research needs to consider the impact of short breaks on fathers.
      Second, there is a need to consider in more depth how short breaks can impact on
      the siblings of disabled children. Third, research could consider how best short
      breaks can be combined with other interventions to maximise the impact for
      disabled children and their families. Fourth, research needs to look at the
      longer term impact of short breaks on outcomes for disabled children and their
      families. What is needed is evidence on what type of short breaks are best for
      children and families with particular characteristics at particular times during
      the course of the child's maturation towards adulthood.

PMID- 21175908
TI  - Determinants of age-dependent change in a secondary sexual character.
AB  - Many secondary sexual characters vary in a systematic way with the age of
      individuals, with young and old individuals displaying at lower levels than
      individuals of intermediate age. Analyses quantifying the within-individual and
      among-individual components of phenotypic variation can help partition effects of
      phenotypic plasticity and selective mortality. We analysed phenotypic variation
      in the expression of a secondary sexual character, tail length, in male and
      female barn swallows Hirundo rustica from four European populations studied
      during 11-26 years, using linear mixed effect models to describe age-related
      expression. Tail length increased from yearlings to intermediate aged birds with
      a subsequent decrease at old age. In males, this age-related pattern was because
      of both within-subject and between-subject effects, with no difference among
      populations. Males having longer lifespan had shorter tails when young than those
      having shorter lifespan. Females showed similar patterns of age-related variation
      as males, with no difference among populations. The major difference between
      sexes was that the between-subject effects (i.e. disappearance effects or
      selection) were much more important for males compared to females for which
      lifetime variation in tail length was mainly because of a within-subject effect
      (i.e., a plastic response). These findings suggest that whereas males trade
      greater expression of the secondary sexual character at young age against
      longevity, that was not the case for females. This is consistent with tail length
      being more costly in males than in females, with the cost of long tails
      potentially being offset by elevated mating success, whereas that is not the case
      in females.

PMID- 21175909
TI  - Post-pleistocene demographic history of the North Atlantic endemic Irish moss
      Chondrus crispus: glacial survival, spatial expansion and gene flow.
AB  - Range expansions and gene flow as micro-evolutionary processes played a leading
      role in the population demographic history of marine organisms. Herein, we
      sequenced partial mtDNA Cox1 gene from 26 assigned geographical populations to
      understand how Irish moss (Chondrus crispus) responded to severe climatic
      oscillations during the Pleistocene glaciations and contemporary forces such as
      gene flow. Phylogeographic patterns indicated that haplotype frequency
      distributions were strongly skewed, with nearly half found only in single samples
      and thus restricted to a single population. Analysis of molecular variance
      revealed that most of the variation was within populations with no significant
      genetic structuring on either side of the Atlantic. Demographic analyses
      indicated that ISI (Irish Sea and Ireland) and NS (the North Sea) areas
      experienced a slight trend of increase in population size over time, whereas EC
      (the English Channel) area experienced expansion beginning approximately 170,000
      360,000 BP. The observed complex genetic pattern of C. crispus is consistent with
      a scenario of multiple unrelated founding events by survival of this species in
      at least three putative Pleistocene refugia along the European coastline, and
      subsequent trans-Atlantic dispersal combined with contiguous northward population
      expansion predating the LGM and geographically gene flow.

PMID- 21175910
TI  - Species range expansion by beneficial mutations.
AB  - A species' range can be limited when there is no genetic variation for a trait
      that allows for adaptation to more extreme environments. We study how range
      expansion occurs by the establishment of a new mutation that affects a
      quantitative trait in a spatially continuous population. The optimal phenotype
      for the trait varies linearly in space. The survival probabilities of new
      mutations affecting the trait are found by simulation. Shallow environmental
      gradients favour mutations that arise nearer to the range margin and that have
      smaller phenotypic effects than do steep gradients. Mutations that become
      established in shallow environmental gradients typically result in proportionally
      larger range expansions than those that establish in steep gradients. Mutations
      that become established in populations with high maximum growth rates tend to
      originate nearer to the range edge and to cause relatively smaller range
      expansion than mutations that establish in populations with low maximum growth
      rates. Under plausible parameter values, mutations that allow for range expansion
      tend to have large phenotypic effects (more than one phenotypic standard
      deviation) and cause substantial range expansions (15% or more). Sexual
      reproduction allows for larger range expansions and adaptation to more extreme
      environments than asexual reproduction.

PMID- 21175911
TI  - Two reproductively isolated cytotypes and a swarm of highly inbred, disconnected
      populations: a glimpse into Salicornia's evolutionary history and challenging
      taxonomy.
AB  - The main factor of differentiation at six nuclear microsatellite and seven cpDNA
      loci in Salicornia from the Mediterranean and Atlantic coasts of France is
      cytotypic identity, suggesting the presence of a strong reproductive barrier
      among sympatric cytotypes. Within cytotypes, a substantial proportion of the
      differentiation between species is due to confounded phylogeographic signal.
      Conspecific individuals tend to be significantly more related than individuals
      from different species at the population scale, but mean kinship coefficients
      among pairs of conspecific and nonconspecific individuals from different
      populations are not significantly different, suggesting the absence of
      reproductive isolation among species of the same cytotype. The observed
      association between morphology and genetic variation within populations would
      thus result from the selfing mating system (F(is)) = 0.70) generating substantial
      linkage within the genome, linkage that would quickly disappear among unrelated
      individuals from different populations. Salicornia species thus function as a
      network of inbred populations, strongly challenging taxonomic concepts.

PMID- 21175912
TI  - The effect of sex on the mean and variance of fitness in facultatively sexual
      rotifers.
AB  - The evolution of sex is a classic problem in evolutionary biology. While this
      topic has been the focus of much theoretical work, there is a serious dearth of
      empirical data. A simple yet fundamental question is how sex affects the mean and
      variance in fitness. Despite its importance to the theory, this type of data is
      available for only a handful of taxa. Here, we report two experiments in which we
      measure the effect of sex on the mean and variance in fitness in the monogonont
      rotifer, Brachionus calyciflorus. Compared to asexually derived offspring, we
      find that sexual offspring have lower mean fitness and less genetic variance in
      fitness. These results indicate that, at least in the laboratory, there are both
      short- and long-term disadvantages associated with sexual reproduction. We
      briefly review the other available data and highlight the need for future work.

PMID- 21175913
TI  - Ant aggression and evolutionary stability in plant-ant and plant-pollinator
      mutualistic interactions.
AB  - Mutualistic partners derive a benefit from their interaction, but this benefit
      can come at a cost. This is the case for plant-ant and plant-pollinator
      mutualistic associations. In exchange for protection from herbivores provided by
      the resident ants, plants supply various kinds of resources or nests to the ants.
      Most ant-myrmecophyte mutualisms are horizontally transmitted, and therefore,
      partners share an interest in growth but not in reproduction. This lack of
      alignment in fitness interests between plants and ants drives a conflict between
      them: ants can attack pollinators that cross-fertilize the host plants. Using a
      mathematical model, we define a threshold in ant aggressiveness determining
      pollinator survival or elimination on the host plant. In our model we observed
      that, all else being equal, facultative interactions result in pollinator
      extinction for lower levels of ant aggressiveness than obligatory interactions.
      We propose that the capacity to discriminate pollinators from herbivores should
      not often evolve in ants, and when it does it will be when the plants exhibit
      limited dispersal in an environment that is not seed saturated so that each seed
      produced can effectively generate a new offspring or if ants acquire an extra
      benefit from pollination (e.g. if ants eat fruit). We suggest specific mutualism
      examples where these hypotheses can be tested empirically.

PMID- 21175905
TI  - A simple and distinctive microbiota associated with honey bees and bumble bees.
AB  - Specialized relationships with bacteria often allow animals to exploit a new diet
      by providing a novel set of metabolic capabilities. Bees are a monophyletic group
      of Hymenoptera that transitioned to a completely herbivorous diet from the
      carnivorous diet of their wasp ancestors. Recent culture-independent studies
      suggest that a set of distinctive bacterial species inhabits the gut of the honey
      bee, Apis mellifera. Here we survey the gut microbiotae of diverse bee and wasp
      species to test whether acquisition of these bacteria was associated with the
      transition to herbivory in bees generally. We found that most bee species lack
      phylotypes that are the same or similar to those typical of A. mellifera,
      rejecting the hypothesis that this dietary transition was symbiont-dependent. The
      most common bacteria in solitary bee species are a widespread phylotype of
      Burkholderia and the pervasive insect associate, Wolbachia. In contrast, several
      social representatives of corbiculate bees do possess distinctive bacterial
      phylotypes. Samples of A. mellifera harboured the same microbiota as in previous
      surveys, and closely related bacterial phylotypes were identified in two Asian
      honey bees (Apis andreniformis and Apis dorsata) and several bumble bee (Bombus)
      species. Potentially, the sociality of Apis and Bombus species facilitates
      symbiont transmission and thus is key to the maintenance of a more consistent gut
      microbiota. Phylogenetic analyses provide a more refined taxonomic placement of
      the A. mellifera symbionts.

PMID- 21175914
TI  - Offer of a weight management program to overweight and obese weight-concerned
      smokers improves tobacco dependence treatment outcomes.
AB  - Weight concern is a common and significant barrier to abstinence for many
      smokers. This quasi-experimental pilot study used multivariate logistic
      regression to examine the effects of offering a weight management treatment
      program on tobacco dependence treatment outcomes. Age, gender, ethnicity,
      educational level, nicotine dependence level, body mass index, and concern about
      weight gain were entered as factors/covariates to account for differences between
      groups. Offering a weight management program increased attendance at the first
      scheduled contact (88.1% vs. 71.6%; OR = 2.93; p = .029) and increased 6-month
      abstinence (21.4% vs. 10.1%; OR = 2.42; p = .052). With factors and covariates
      included in the multivariate models to account for group differences, those
      offered weight management were five times more likely to attend their first
      session (OR = 5.10; 95% CI 1.53-16.98; p = .008) and three times more likely to
      be abstinent 6 months after tobacco treatment (OR = 2.98; 95% CI = 1.09-8.17; p =
      .033). Proactively informing weight-concerned, overweight/obese smokers about the
      availability of a weight management program as an incentive for completing
      treatment for tobacco dependence may improve tobacco treatment outcomes. 

PMID- 21175916
TI  - Compulsive alcohol use and other high-risk behaviors among college students.
AB  - The association between heavy alcohol consumption and risky behaviors has been
      amply investigated among college students. However, less is known with regard to
      types of drinking behaviors associated with high-risk activities. The present
      study extends this area of research by examining the relationship between
      compulsive drinking and hazardous behaviors in this population. Nine hundred and
      four college students completed measures on compulsive drinking and other risky
      behaviors in the context of mental health screenings at three campuses. Results
      showed that in males, compulsive drinking increased the risk for compulsive
      street drugs use, compulsive prescription drugs use, compulsive sexual
      activities, and gambling. Among females, compulsive drinking increased the risk
      for compulsive street drugs use, and compulsive sexual activities. These findings
      suggest that inquiring about compulsive drinking among college students may have
      great utility in identifying those at greater risk for other risky behaviors. The
      high co-occurrence of compulsive drinking, illicit substances, compulsive sexual
      activities, and gambling in college students suggests the need for comprehensive
      programs addressing high-risk behaviors together.

PMID- 21175915
TI  - Human growth hormone abuse in male weightlifters.
AB  - In a study of performance-enhancing substance use among 231 experienced young
      male weightlifters, we found that 27 (12%) reported illicit use of human growth
      hormone (HGH) or its bioactive derivative, insulin-like growth factor-1. All of
      these 27 men also reported use of anabolic-androgenic steroids (AAS) and 22 (81%)
      met criteria for current or past AAS dependence. Fifteen (56%) also reported
      current or past dependence on opioids, cocaine, and/or ecstasy. These findings
      suggest that among young male weightlifters, illicit HGH use has become a common
      form of substance abuse, frequently associated with both AAS dependence and
      classical substance dependence. 

PMID- 21175917
TI  - Patterns and predictors of alcohol use in male and female urban police officers.
AB  - In a large sample of urban police officers, 18.1% of males and 15.9% of females
      reported experiencing adverse consequences from alcohol use and 7.8% of the
      sample met criteria for lifetime alcohol abuse or dependence. Female officers had
      patterns of alcohol use similar to male officers and substantially more than
      females in the general population. Critical incident exposure and posttraumatic
      stress disorder (PTSD) symptoms were not associated with level of alcohol use.
      Greater psychiatric symptoms were related to adverse consequences from alcohol
      use. There was a noteworthy gender by work stress interaction: greater routine
      work stress related to lower current alcohol use in female officers. 

PMID- 21175918
TI  - A web-based study of gamma hydroxybutyrate (GHB): patterns, experiences, and
      functions of use.
AB  - GHB (gamma hydroxybutyrate) was developed as a general anesthetic. Due to dosing
      difficulty and side effects, regular use was discontinued. Medical uses include
      treating sleep and alcohol disorders. In the 1990s, it was promoted as a
      supplement and taken to improve mood and sex. GHB and its analogs (gamma
      butyrolactone and butanediol) were widely available until federal regulations
      were put into effect with mounting evidence of adverse events. This survey (N =
      61) study was conducted to assess patterns, experiences, and functions of use.
      Much of what is understood regarding GHB treatment is based on hospital case
      studies for overdose and withdrawal. Not enough is known about prevention,
      reducing use and associated problems, or relapse. We know little about specific
      drug effect expectancies, triggers, coping skills, and consequences of use
      (positive/negative). While the drug treatment literature has a wealth of
      information to draw upon, GHB-specific information may greatly assist relapse
      prevention. 

PMID- 21175919
TI  - Utilization of residential alcoholism treatment in bipolar disorder.
AB  - Despite the high prevalence rate of comorbid alcohol dependence and bipolar
      disorder, little is known about how many bipolar patients are actively engaged in
      addiction treatment or the alcohol consumption characteristics of this group.
      This retrospective study reviewed the medical records from patients with alcohol
      dependence admitted to residential treatment at our institution (n = 588). The
      analyses focused on alcoholism severity measures and discharge clinical
      diagnoses. Patients with alcoholism + bipolar disorder compromised only 5% of the
      total study group. The number of drinking years was lower for patients with
      alcoholism + bipolar disorder (23.1 +/- 17.7) than for those with alcoholism +
      depression (26.8 +/- 13.9) or alcoholism alone (28.1 +/- 13.2). A trend of higher
      mean lifetime maximum daily drinks was observed for patients with alcoholism +
      bipolar disorder; this was because of the significantly higher maximum drinks for
      women with bipolar disorder (21.0 +/- 11.5) than for women in other diagnostic
      groups. Despite high rates of comorbidity in community-based studies, this
      retrospective study suggests that patients with bipolar disorder are not highly
      represented in residential alcoholism addiction treatment. Future studies are
      encouraged to better understand utilization rates of addiction treatment among
      patients with bipolar disorder and to identify clinical correlates that
      predispose bipolar women to high-dose drinking. 

PMID- 21175920
TI  - The tobacco-dependence clinic: intensive tobacco-dependence treatment in an
      addiction services outpatient setting.
AB  - We present outcomes from an intensive tobacco-dependence treatment program for
      addiction services clients at three different sites. Data from 202 participants
      were analyzed. For individuals who completed the program, the abstinence rate was
      43%. Not having a primary substance use history and a lower carbon monoxide (CO)
      level at intake predicted abstinence; whereas being female, the particular site
      of intervention, receiving both nicotine replacement therapy (NRT) and oral
      medication, and having a lower CO level at baseline predicted program completion.
      Drug treatment clients can successfully quit smoking at rates similar to the
      general population when given access to intensive tobacco-dependence treatment. 

PMID- 21175921
TI  - Counselors' knowledge of the adoption of tobacco cessation medications in
      substance abuse treatment programs.
AB  - This study assessed counselors' knowledge of the adoption of evidence-based
      tobacco cessation medications (TCMs)--varenicline, bupropion, and five nicotine
      replacement therapies (NRTs)--and predictors of adoption in diverse substance
      abuse treatment settings. We used Managing Effective Relationships in Treatment
      Services (MERITS I) data from 658 counselors working in 26 programs. Adoption of
      varenicline was reported by 16% of counselors, bupropion by 11%, and NRTs by 27%.
      Knowledge of the adoption of all types of TCMs was more likely to be reported by
      counselors who worked in treatment programs that adhered less to a 12-step
      orientation and restricted outdoor smoking for employees. Several additional
      unique predictors of varenicline and NRTs were identified. 

PMID- 21175922
TI  - Daily telephone monitoring compared with retrospective recall of alcohol use
      among patients in early recovery.
AB  - Most studies comparing frequent self-monitoring protocols and retrospective
      assessments of alcohol use find good correspondence, but have excluded
      participants with significant comorbidity and/or social instability, and some
      have included abstainers. We evaluated the correspondence between measures of
      alcohol use based on daily interactive voice response (IVR) telephone monitoring
      and a 28-day modification of the Form-90 (Form-28). Participants were 25
      outpatients with alcohol use disorder and significant PTSD symptomatology .
      Overall correlations between the IVR and Form-28 on days drinking and total
      standard drink units (SDUs) were strong for the entire sample and the subsample
      of drinkers (n = 7). Day-to-day correspondence between IVR and Form-28 was
      modest, but much stronger for the most recent week assessed than for the prior 3
      weeks. Finally, the drinkers reported significantly greater total SDUs and heavy
      drinking days on the Form-28 than via IVR. The results indicate a need for
      further refinement of IVR methodology for treatment seeking populations as well
      as caution when retrospectively assessing drinking over time periods longer than
      a week among these individuals. 

PMID- 21175923
TI  - Differences in the associations between gambling problem severity and psychiatric
      disorders among black and white adults: findings from the National Epidemiologic
      Survey on Alcohol and Related Conditions.
AB  - We examined differences in the associations of gambling problem severity and
      psychiatric disorders among a nationally representative sample of 32,316 black
      and white adults. Black respondents were more likely than white ones to exhibit
      problem or pathological gambling (PPG) and a stronger relationship between
      subsyndromal gambling and any mood disorder, hypomania, and any substance use
      disorder. Differences in the patterns of co-occurring disorders between syndromal
      and particularly subsyndromal levels of gambling in black and white respondents
      indicate the importance of considering race-related factors in mental health
      prevention and treatment strategies. 

PMID- 21175925
TI  - A novel online didactic curriculum helps improve knowledge acquisition among non
      emergency medicine rotating residents.
AB  - OBJECTIVES: Rotating residents represent a significant proportion of housestaff
      in academic emergency departments (EDs), yet they rarely receive targeted
      didactic education during their emergency medicine (EM) rotations. The goals of
      this study were: 1) to determine the effectiveness of an online didactic
      curriculum in improving EM knowledge among rotating residents and 2) to assess
      rotating resident satisfaction with this curriculum. METHODS: The authors created
      an online lecture series of six EM subject areas targeted to rotating residents
      called the Northwestern University Rotating Resident Curriculum (NURRC). All
      rotating residents at the study site were eligible, written consent was obtained,
      and the study was approved by the institutional review board. Consenting
      participants were pretested with a 42-question multiple-choice examination and
      then randomized to two groups: one with access to the NURRC during the first 2
      weeks of the rotation (experimental) and one without (control). Halfway through
      the rotation, all participants were post-tested with a different multiple-choice
      examination, and the controls were then granted NURRC access. The primary outcome
      was the difference between pretest and posttest scores (score delta). The t-test
      was used to compare mean scores, and a linear regression model was used to
      determine the association of NURRC access on score delta after adjustment for
      pretest type and resident type. A postintervention survey was administered at the
      end of the rotation to assess satisfaction with the NURRC and collect suggestions
      for improvement. RESULTS: Fifty-four rotating residents were enrolled: 29 in the
      experimental group and 25 in the control group. There was no significant
      difference in pretest scores between the two groups. Mean score delta was 17.3%
      in the experimental group and 1.6% in the control group, an absolute difference
      of 15.7% (95% confidence interval [CI]=10% to 22%). After adjustment for resident
      type and pretest type, the only variable positively associated with the primary
      outcome was NURRC access. Third-year and preliminary-year internal medicine (IM)
      residents demonstrated the greatest absolute improvement in score delta when
      granted NURRC access. Eighty percent of the participants responded to the
      satisfaction survey. Over 80% of the survey respondents approved of each
      component lecture and of the NURRC overall. CONCLUSIONS: After exposure to an
      online didactic curriculum, rotating residents demonstrated a significant
      increase in EM knowledge and reported a high level of satisfaction with the
      didactic program.

PMID- 21175924
TI  - Decision-making deficits linked to real-life social dysfunction in crack cocaine
      dependent individuals.
AB  - Crack cocaine-dependent individuals (CCDI) present abnormalities in both social
      adjustment and decision making, but few studies have examined this association.
      This study investigated cognitive and social performance of 30 subjects (CCDI *
      controls); CCDI were abstinent for 2 weeks. We used the Social Adjustment Scale
      (SAS), Wisconsin Card Sorting Test (WCST), and Iowa Gambling Task (IGT).
      Disadvantageous choices on the IGT were associated with higher levels of social
      dysfunction in CCDI, suggesting the ecological validity of the IGT. Social
      dysfunction and decision making may be linked to the same underlying prefrontal
      dysfunction, but the nature of this association should be further investigated. 

PMID- 21175926
TI  - Radiation screening.

PMID- 21175927
TI  - Direct observation of clinical practice in emergency medicine education.
AB  - This review aims to summarize the current literature on the effects of direct,
      clinical observation of residents in emergency departments (EDs) on learners,
      patients, and departmental functioning. A systematic literature search was
      conducted in Medline and ERIC, covering the years 1980-2009. Keywords were used
      to identify postgraduate medical staff working in the ED; direct observation of
      these trainees by supervising staff; and reports of outcomes relating to
      Kirkpatrick's levels of reaction, learning, behavior, and institutional change.
      From an initial 11,433 abstracts and titles, 193 full-text articles were
      retrieved for further study. Application of inclusion and exclusion criteria
      yielded seven that were relevant to the topic. These studies comprised a range of
      methods--descriptive, qualitative evaluation, cohort studies, and a cross
      sectional survey. Learner reaction was very enthusiastic. Positive changes in
      behavior due to feedback provided during direct observation were suggested by two
      studies. A single study evaluated trainee's perceptions on patient outcomes and
      noted that thorough assessments and improved management decisions may be at the
      expense of slower throughput of patients and diversion of senior staff from
      direct patient care. Three studies noted the resource-intensive nature of direct
      observation. Direct observation of clinical practice may be useful in ED
      education; however, further research is required to evaluate its effects.

PMID- 21175928
TI  - Words: the "drug" with the highest frequency of dispensing errors.
AB  - Effective communication is the key component of every patient-physician encounter
      and is essential for shared decision-making. "Words" are perhaps the most
      frequently dispensed "drug," while communication is the most frequently performed
      "procedure" in emergency medicine. Yet, communication skills are often learned by
      trial and error, as opposed to the methodical approach followed for teaching all
      other technical procedures. The case presented below highlights the importance of
      incorporating effective communication skills as tools for our daily practice.

PMID- 21175929
TI  - Glycine and taurine equally prevent fatty livers from Kupffer cell-dependent
      injury: an in vivo microscopy study.
AB  - BACKGROUND: IRI still is a major problem in liver surgery due to warm ischemia
      and organ manipulation. Steatosis is not only induced by diabetes,
      hyperalimentation, alcohol and toxins, but also chemotherapy given before
      resection. Since steatotic livers are prone to Kupffer cell-dependent IRI,
      protection of steatotic livers is of special interest. This study was designed to
      compare the effect of taurine and glycine on IRI in steatotic livers. MATERIALS
      AND METHODS: Steatosis was induced with ethanol (7 g/kg b.w.; p.o.) in female SD
      rats. Ten minutes after inactivation of Kupffer cells with taurine or glycine
      (300 mM; i.v.), left liver lobes underwent 60 minutes of warm ischemia. Controls
      received the same volume of valine (300 mM; i.v.) or normal saline. After
      reperfusion, white blood cell-endothelial interactions and latex-bead
      phagocytosis by Kupffer cells were investigated. Liver enzymes were measured to
      estimate injury. For statistical analysis, ANOVA and Student's t-test were used.
      RESULTS: Glycine and taurine significantly decreased leukocyte- and platelet
      endothelium interactions and latex-bead phagocytosis (p < 0.05). Liver enzymes
      were significantly lower after glycine and taurine (p < 0.05). CONCLUSIONS: This
      study shows that preconditioning with taurine or glycine is equally effective in
      preventing injury to fatty livers most likely via Kupffer cell-dependent
      mechanisms.

PMID- 21175930
TI  - Sequel to Kitzmiller's Anopheline names: their derivations and histories.
AB  - The derivations of the names of 74 Anopheles species and one subgenus are
      explained together with accounts of the life and scientific work of people who
      have been honored by having a mosquito named after them. Descriptive accounts are
      given of geographical locations, whether towns, regions or counties, that have
      had anopheline species named after them.

PMID- 21175931
TI  - Patterns of sugar feeding and host plant preferences in adult males of An.
      gambiae (Diptera: Culicidae).
AB  - Sugar feeding by male mosquitoes is critical for their success in mating
      competition. However, the facets of sugar source finding under natural conditions
      remain unknown. Here, evidence obtained in Western Burkina Faso indicated that
      the distribution of An. gambiae s.s. (M and S molecular forms) males across
      different peri-domestic habitats is dependent on the availability of potential
      sugar sources from which they obtain more favorable sites for feeding or resting.
      Among field-collected anophelines, a higher proportion of specimens containing
      fructose were found on flowering Mangifera indica (Anacardiaceae), Dolonix regia
      (Fabaceae), Thevetia neriifolia (Apocynaceae), Senna siamea, and Cassia
      sieberiana (both Fabaceae) compared to that recorded on other nearby plants,
      suggesting that some plants are favored for use as a sugar source over others. Y
      tube olfactometer assays with newly-emerged An. gambiae s.s. exposed to odors
      from individual plants and some combinations thereof showed that males use odor
      cues to guide their preference. The number of sugar-positive males was variable
      in a no-choice cage assay, consistent with the olfactory response patterns
      towards corresponding odor stimuli. These experiments provide the first evidence
      both in field and laboratory conditions for previously unstudied interactions
      between males of An. gambiae and natural sugar sources.

PMID- 21175932
TI  - Bionomics of Aedes aegypti subpopulations (Diptera: Culicidae) from Argentina.
AB  - Differences in biological features of immature and adult Aedes aegypti, as well
      as variability in vector competence, seem consistent with the existence of
      genetic variation among subpopulations and adaptation to local conditions. This
      work aims to compare the bionomics of four Ae. aegypti subpopulations derived
      from different geographical regions reared under temperate conditions. Life
      statistics of three Ae. aegypti subpopulations from the provinces of Cordoba,
      Salta, and Misiones were studied based on horizontal life tables. The Rockefeller
      strain was used as a control. The development time required to complete the larva
      and pupa stages varied from 6.91 to 7.95 and 1.87 to 2.41 days, respectively.
      Significant differences were found in mean larval development time between the
      Cordoba and Oran subpopulations. The larva-pupa development time was similar in
      all the subpopulations. However, survival values varied significantly between the
      Oran and San Javier subpopulations. The proportion of emergent males did not
      differ from females within each subpopulation nor among them. Adult longevity was
      similar among the subpopulations. The average number of eggs laid by each female
      was significantly different. The Rockefeller strain laid a significantly greater
      number of eggs (463.99 eggs/female) than the rest of the subpopulations.
      Moreover, differences in the demographic growth parameter R(o) were detected
      among the four subpopulations. The differences obtained in larval development
      time, larva-pupa survival values, and net reproductive rates among the
      subpopulations might reflect underlying genetic differences as a result of
      colonization from different regions that probably involve adaptations to local
      conditions.

PMID- 21175933
TI  - Colonization of Lutzomyia shannoni (Diptera: Psychodidae) utilizing an artificial
      blood feeding technique.
AB  - Laboratory colonization of hematophagous insects must include an efficient method
      of blood feeding, preferably by artificial means. Strict rules for obtaining
      animal use permits, extensive animal maintenance costs, and indirect anesthesia
      effects on animal health warrant the development of an artificial membrane
      feeding technique for sand fly colonization in laboratories. An attempt was made
      to colonize Lutzomyia shannoni using an artificial blood feeding membrane to
      replace the use of live animals commonly used for sand fly blood-feeding
      purposes. Lutzomyia shannoni readily fed through a pig intestine membrane exposed
      at an angle of 45 degrees . However, it did not feed through a chicken skin
      membrane. Olfactory attractants were unable to improve blood-feeding efficiency.
      Plaster of Paris was the most suitable oviposition substrate. Female L. shannoni
      adults laid no eggs on moist sand substrate. Sand fly adults held in groups of
      ten or more laid higher numbers of eggs than did individually maintained sand
      flies. Inclusion of the L. longipalpis oviposition hormone dodecanoic acid or the
      presence of previously laid eggs did not stimulate L. shannoni oviposition. The
      average L. shannoni egg, larval, and pupal duration were 9.3, 36.7, and 17.8
      days, respectively. The addition of a 20% sugar solution improved adult female
      longevity. Females survived longer (14.8 days) than males (11.9 days). Lutzomyia
      shannoni was successfully colonized in the laboratory for up to four generations
      using this artificial membrane technique.

PMID- 21175934
TI  - Sylvatic and peridomestic populations of Triatoma pseudomaculata are not
      significantly structured by habitat, as revealed by two genetic markers.
AB  - Chagas disease remains a public health concern in Brazil and other Latin American
      countries, mainly due to the potential domiciliation of native triatomine
      species. We analyzed the genetic variability of Triatoma pseudomaculata in
      sylvatic and peridomestic ecotopes throughout three localities in the
      northeastern state of Bahia, Brazil. We studied polymorphisms generated by random
      amplified polymorphic DNA (RAPD) and isoenzyme electrophoresis analyses. Based on
      RAPD analysis, each specimen was assigned to one of three genetic clusters.
      Although all sylvatic specimens from one locality were grouped into the same
      cluster, sylvatic and peridomestic specimens from the other two localities were
      broadly distributed between the remaining two clusters, suggesting that
      geographic population structuring was not occurring. Furthermore, isoenzyme
      analysis suggested that distinct populations were in Hardy-Weinberg equilibrium.
      Low statistical values for Wright's Fst index also supported the absence of
      population structuring and suggested the occurrence of panmixia. We conclude that
      genetic flow occurs between sylvatic and peridomestic T. pseudomaculata
      populations, probably as a consequence of passive and active dispersion of the
      insects, associated with deforestation and anthropic transformations.

PMID- 21175935
TI  - Aedes albopictus (Diptera: Culicidae) oviposition response to organic infusions
      from common flora of suburban Florida.
AB  - We evaluated the oviposition response of gravid Aedes albopictus (Skuse) to six
      organic infusions. Laboratory and field-placed oviposition cups baited with water
      oak (Quercus nigra L.), longleaf pine (Pinus palustris P. Mill), or St. Augustine
      grass (Stenotaphrum secundatum (Walt.) Kuntze), as well as binary infusion
      mixtures of each, were used. In addition, a triple-cage, dual port olfactometer
      was used to measure upwind response of gravid individuals to these infusions. We
      found that Ae. albopictus deposited more eggs in infusion-baited cups compared
      with water alone. Moreover, significantly more eggs were laid in the water oak
      and a water oak-pine mixture as compared with the St. Augustine grass infusion in
      laboratory bioassays. However, a negative upwind response was observed with
      longleaf pine infusion in the olfactometer. In field cages, significantly more
      eggs were deposited in infusion-baited cups as compared with water alone and a
      greater percentage of eggs were deposited in cups containing a water oak and the
      water oak-longleaf pine mixture as compared with cups containing single infusions
      or their mixtures.

PMID- 21175936
TI  - Mosquito fauna on the Cape Verde Islands (West Africa): an update on species
      distribution and a new finding.
AB  - To evaluate the risk of transmission of vector-borne diseases, regular updates of
      the geographic distribution of insect vectors are required. In the archipelago of
      Cape Verde, nine mosquito species have been reported. Of these, four are major
      vectors of diseases that have been present in the archipelago: yellow fever,
      lymphatic filariasis, malaria and, currently, an outbreak of dengue. In order to
      assess variation in mosquito biodiversity, we have carried out an update on the
      distribution of the mosquito species in Cape Verde, based on an enquiry of 26
      unpublished technical reports (1983-2006) and on the results of an entomological
      survey carried out in 2007. Overall, there seems to be a general trend for an
      expansion of biological diversity in the islands. Mosquito species richness was
      negatively correlated with the distance of the islands from the mainland but not
      with the size of the islands. Human- and/or sporadic climatic-mediated events of
      dispersal may have contributed to a homogenization of species richness regardless
      of island size but other ecological factors may also have affected the mosquito
      biogeography in the archipelago. An additional species, Culex perexiguus, was
      collected for the first time in the archipelago during the 2007 survey.

PMID- 21175937
TI  - Dissemination of western equine encephalomyelitis virus in the potential vector,
      Culex pipiens pallens.
AB  - Two western equine encephalomyelitis virus (WEEV) strains have been isolated in
      China. Our previous studies have verified that the mosquito Culex pipiens pallens
      Coquillett (Diptera: Culicidae) infected with WEEV was capable of transmitting
      this arbovirus, but it was not clear how the sequential multiplication and spread
      of virus occurred within the mosquito. In this study, we observed the
      distribution of WEEV antigen in orally-infected Cx. p. pallens by
      immunohistochemistry in order to better understand the initial infection,
      dissemination, and transmission of WEEV in the potential vector. Orally-infected
      WEEV dissemination varied within the different tissues of Cx. p. pallens, with
      virus antigen consistently observed in the salivary glands, foregut, midgut
      epithelial cells, Malpighian tubules, hindgut, and ovarian follicles of some
      individuals after various days of extrinsic incubation. We suggest that Cx. p.
      pallens, the potential vector of WEEV, has the ability to harbor the virus
      through the alimentary system, and the midgut epithelial cell may be the initial
      site of WEEV replication after ingestion of a viremic blood meal.

PMID- 21175938
TI  - Laboratory evaluation of lactic acid on attraction of Culex spp. (Diptera:
      Culicidae).
AB  - The role of lactic acid was evaluated for attraction of Culex nigripalpus, Culex
      quinquefasciatus, Culex tarsalis, and Aedes aegypti in the laboratory using a
      dual-port olfactometer. When lactic acid was combined with chicken odor,
      attraction was increased for Cx. quinquefasciatus compared to chicken odor alone
      but not for Cx. nigripalpus, Cx. tarsalis, and Ae. aegypti. Lactic acid combined
      with hand odor did not change attraction of Cx. tarsalis and Ae. aegypti but
      decreased attraction of Cx. nigripalpus and Cx. quinquefasciatus. The addition of
      lactic acid to CO(2) increased attraction of Ae. aegypti and Cx. quinquefasciatus
      but reduced attraction of Cx. nigripalpus and Cx. tarsalis. Use of commercial
      lactic acid baits with CO(2) resulted in a similar trend except for Cx.
      nigripalpus which showed no difference. A blend of lactic acid, acetone, and
      dimethyl disulfide was attractive to Ae. aegypti (63.4%) but elicited low
      responses by all Culex spp. (1.3-26.8%). Addition of the blend to CO(2) increased
      attraction of Ae. aegypti and Cx. quinquefasciatus but reduced attraction of Cx.
      nigripalpus and Cx. tarsalis. The mixture of compounds plus CO(2) was as
      attractive as a hand for Cx. quinquefasciatus, Cx. tarsalis, and Ae. aegypti.

PMID- 21175939
TI  - Richness and diversity of sand flies (Diptera, Psychodidae) in an Atlantic
      rainforest reserve in southeastern Brazil.
AB  - Our objective was to study and evaluate the richness and diversity of
      Phlebotominae fauna in the Duas Bocas Biological Reserve (DBBR) in the state of
      Espirito Santo, in southeastern Brazil. Sand fly collections were carried out
      during four consecutive nights each month between August 2007 and July 2008 at
      DBBR by using CDC automatic light traps and an illuminated Shannon trap. Specific
      richness (S) and Shannon diversity index (H) was calculated for each trap. We
      collected 18,868 sand flies belonging to 29 species and 13 genera. Nyssomyia
      yuilli yuilli was the most abundant species followed by Psychodopygus ayrozai,
      Ps. hirsutus, Psathyromyia pascalei, and Ps. matosi. We recorded Brumptomyia
      cardosoi, Br. troglodytes, and Ps. geniculatus for the first time in the state of
      Espirito Santo. We discuss the differences in diversity and richness of the sand
      flies in both traps and in relation to other Brazilian localities and biomes. We
      also discuss the possibility of wild transmission of Leishmania in the DBBR and
      the influence of the sand fly species in leishmaniasis transmission to the
      adjacent areas of the reserve.

PMID- 21175940
TI  - Unsuitability of Cnesterodon decemmaculatus (Jenyns, 1842) for mosquito control
      in Uruguay: evidence from food-preference experiments.
AB  - We analyzed the feeding preference of Cnesterodon decemmaculatus, a small-bodied
      poecilid native from the Rio de la Plata and proximate Atlantic Basins in South
      America. This species has a wide distribution in Uruguayan water bodies but its
      effectiveness as a predator of mosquito larvae has not been tested. In laboratory
      trials, five aquatic invertebrates were offered simultaneously as potential prey
      to fish: Daphnia pulex (Cladocera), copepods, two different instars of mosquito
      larvae (Culex pipiens), and the 4th instar of Chironomidae larvae. Preference was
      measured by the Chesson's electivity index (alpha). In order to determine
      differences in prey preference according to fish size, individuals ranging from
      9.5 mm to 35.3 mm were classified in three different body size classes: small,
      medium, and large. Small fish showed preference for copepods, while medium-sized
      fish preferred the smallest mosquito larvae instars and Chironomidae larvae. We
      conclude that C. decemmaculatus is a zooplankton facultative-feeder fish that
      prefers large-bodied zooplankton but is a weak predator of mosquito larvae. Thus,
      the introduction of C. decemmaculatus as a biological-control agent in natural
      environments is not an effective strategy.

PMID- 21175941
TI  - The association between meteorological variables and the abundance of Aedes
      taeniorhynchus in the Florida Keys.
AB  - The black salt marsh mosquito, Aedes taeniorhynchus, is a serious nuisance pest
      and a potential vector of a number of arboviruses. This study examined the effect
      of wind direction, wind speed, temperature, and time of year on the abundance of
      Ae. taeniorhynchus collected in CO2 -baited light traps at 12 sites in the
      Florida Keys during 2004. The dependent variable analyzed was the natural log of
      weekly mosquito abundance. The previous week's wind speed and wind direction, and
      the current week's temperature were used as independent variables. Simple and
      multiple linear regression models were used to assess the significance and nature
      of association between the meteorological variables and the natural log of
      mosquito abundance, and to determine whether the meteorological variables had
      significant associations with mosquito abundance after also controlling for time
      of year. Week of year was treated as a circular independent variable in the
      regression models, using the sine and cosine of week in radians to model the
      periodic seasonal fluctuation in mosquito abundance. Mosquito abundance was
      significantly associated with all meteorological variables and with week of year.
      Individually, previous week's wind speed and wind direction, and current week's
      temperature were able to explain respectively 24.5%, 24.5%, and 52.1% of the
      variation in mosquito abundance observed over the year. Week of year had the
      strongest individual association with mosquito abundance, explaining 65.7% of the
      variation in mosquito abundance. The meteorological variables were still
      significantly associated with mosquito abundance, after controlling for week of
      year. Week and the meteorological variables together explained 79.2% of the
      variation in mosquito abundance. The regression models fit to the data from this
      study suggest a strong periodic seasonal variation in mosquito abundance, with
      meteorological conditions explaining a significant portion of the variation
      beyond the seasonal trend.

PMID- 21175942
TI  - The influence of aquatic predators on mosquito abundance in animal drinking
      troughs in New Zealand.
AB  - The occurrence and abundance of mosquito populations may be associated with the
      abundance of predators. We examined the relationship between aquatic predators
      and populations of mosquitoes in animal water troughs in Waikanae, New Zealand.
      We also investigated the effects of water volume and environmental factors
      (temperature, rainfall, wind speed, humidity, and pressure) in order to further
      understand factors influencing mosquito and predator populations. Logistic
      regression indicated that the presence or absence of mosquitoes was primarily
      affected by three factors: predator abundance, week of observation, and water
      volume. Pearson's correlation indicated that the presence of predators had a
      positive correlation with water volume (r2 = 0.176, p< 0.05). Otherwise, the
      presence of mosquito larvae in water troughs was negatively correlated with water
      volume (r2 =-0.159, p=0.022) and wind speed (r2 =0.142, p=0.041). We established
      a translocation experiment in which predators or mosquitoes were moved between
      troughs in order to examine the prey survival rate after exposure to Anisops
      wakefieldi predators. The survival rate of mosquitoes was not significantly
      different, between 0-0.1%, irrespective of the number of predators translocated
      (1-9) or the initial mosquito density (20-70 larvae). Our results suggested that
      A. wakefieldi predators may have the potential to be a promising biological
      control tool for the control of mosquito populations by altering mosquito
      population dynamics.

PMID- 21175943
TI  - Estimating reaction norms for predictive population parameters, age specific
      mortality, and mean longevity in temperature-dependent cohorts of Culex
      quinquefasciatus Say (Diptera: Culicidae).
AB  - Culex quinquefasciatus plays a major role in the transmission of important
      parasites and viruses throughout the world. Because temperature is an important
      limiting factor on growth and longevity of all mosquito species, estimating the
      reaction norms provides very important basic information for understanding both
      plasticity and individual variations of the population. In the present study, Cx.
      quinquefasciatus were maintained at five different constant temperatures (15
      degrees , 20 degrees , 23 degrees , 27 degrees , and 30 degrees C) for two
      subsequent generations. Reproductive population parameters in blood-fed mated
      females and longevities of virgin and blood-fed mated adults reared at different
      temperatures were compared for the two generations. Longevity increased as
      temperature decreased within a range of 15 degrees  to 30 degrees C for the
      unmated adults, and 15 degrees  to 27 degrees C for the mated and blood-fed
      adults. Generation times were as long as 124.07 and 106.76 days for two
      subsequent generations reared at 15 degrees C, and the highest intrinsic rate of
      increase (r(m)) values were estimated at 0.22 and 0.18, respectively, from the
      cohorts reared at 27 degrees C. For survival rates, reproductive rates (R0), and
      r(m) values, 30 degrees C was found to be a critical temperature for this
      species. These cohorts produced the smallest amount of eggs (R0 = 5.06), r(m)
      values decreasing across generations (from 0.11 to 0.06), and the survival rates
      from egg to adult were found to be insufficient (16.1 and 10.8%). Additionally,
      the rate of exponential increase with age and age specific mortalities (b) were
      calculated for the virgin cohorts. Age specific mortality rates increased as
      temperature decreased. The increase in mortality rates started to accelerate at
      27 degrees C and was more pronounced at 30 degrees C, for both females and males.
      We estimated the coefficients of variation for the b values in which females have
      smaller coefficients than those of the males at all temperatures.

PMID- 21175944
TI  - Polymerase chain reaction (PCR) identification of rodent blood meals confirms
      host sharing by flea vectors of plague.
AB  - Elucidating feeding relationships between hosts and parasites remains a
      significant challenge in studies of the ecology of infectious diseases,
      especially those involving small or cryptic vectors. Black-tailed prairie dogs
      (Cynomys ludovicianus) are a species of conservation importance in the North
      American Great Plains whose populations are extirpated by plague, a flea
      vectored, bacterial disease. Using polymerase chain reaction (PCR) assays, we
      determined that fleas (Oropsylla hirsuta) associated with prairie dogs feed upon
      northern grasshopper mice (Onychomys leucogaster), a rodent that has been
      implicated in the transmission and maintenance of plague in prairie-dog colonies.
      Our results definitively show that grasshopper mice not only share fleas with
      prairie dogs during plague epizootics, but also provide them with blood meals,
      offering a mechanism by which the pathogen, Yersinia pestis, may be transmitted
      between host species and maintained between epizootics. The lack of identifiable
      host DNA in a significant fraction of engorged Oropsylla hirsuta collected from
      animals (47%) and prairie-dog burrows (100%) suggests a rapid rate of digestion
      and feeding that may facilitate disease transmission during epizootics but also
      complicate efforts to detect feeding on alternative hosts. Combined with other
      analytical approaches, e.g., stable isotope analysis, molecular genetic
      techniques can provide novel insights into host-parasite feeding relationships
      and improve our understanding of the role of alternative hosts in the
      transmission and maintenance of disease.

PMID- 21175945
TI  - Evaluation of nontarget effects of methoprene applied to catch basins for
      mosquito control.
AB  - The mosquito larvicide methoprene is a juvenile growth hormone mimic that is
      widely used to control mosquito larvae in stormwater catch basins. This study
      addresses two concerns pertaining to methoprene's use for mosquito control.
      First, measurements of methoprene concentrations were made from water in catch
      basins that had been treated with methoprene and from an adjoining salt pond near
      where the treated catch basins emptied. The concentrations of methoprene in catch
      basins and at drainage outlets after application at the rates currently used for
      mosquito control in southern Rhode Island were 0.5 ppb and lower, orders of
      magnitude below what has been determined as detrimental to organisms other than
      mosquitoes. Second, the effects of methoprene on the communities that live in
      catch basins were evaluated both in simulated catch basins in the laboratory and
      in actual catch basins in the field. We found no evidence of declines in
      abundances of any taxa attributable to the application. Furthermore, we found no
      consistent changes in community-level parameters (e.g., taxonomic richness, and
      dominance-diversity relationships) related to methoprene application in either
      field or laboratory trials.

PMID- 21175946
TI  - Ecology of Triatoma brasiliensis in northeastern Brazil: seasonal distribution,
      feeding resources, and Trypanosoma cruzi infection in a sylvatic population.
AB  - We assessed some ecological parameters of Triatoma brasiliensis in rock piles in
      the state of Ceara during the rainy and dry seasons. The greatest density was in
      April (median = 12.5 triatomines/site). The greatest abundance was in December,
      when the insects were more dispersed and the density per site was lower (6
      triatomines/site). The nutritional status of females and 5th instar nymphs was
      increased in July. The rate of T. cruzi infection reached its highest peak in
      July (10.9%). ELISA revealed that the principal food sources were birds (33.1%),
      followed by armadillos (18.8%). Food sources were more frequently identified
      during the rainy season. T. brasiliensis specimens collected in the drought
      tended to: i) present lower rates of T. cruzi infection and gut content
      reactivity to tested antisera, ii) have a poorer nutritional status, iii) exhibit
      lower fecundity, iv) be more dispersed among the studied collection sites, and v)
      be more abundant and easily collected in the surface of the rocks, possibly
      reflecting an increased searching for blood meals. Such findings underscore
      epidemiological concerns and allow inferences about the season when triatomines
      can more frequently invade the peridomestic environment in search of food and
      recolonize artificial structures.

PMID- 21175947
TI  - Efficacy of sticky and standard ovitraps for Aedes aegypti in Trinidad, West
      Indies.
AB  - The double sticky trap (DST) is described for the first time and is evaluated
      along with standard ovitraps and sticky traps (STs) to determine population
      densities of Ae. aegypti in the urban township of St. Augustine and the rural
      community of Tamana, Trinidad, West Indies. Ten houses were selected at each
      study site. At each of the ten houses, one ovitrap, one ST, and one DST were
      placed using the criteria established for placement of ovitraps. The results
      showed the three trapping methods successfully collected Ae. aegypti mosquitoes.
      All three traps collected significantly more adults or eggs in St. Augustine than
      in Tamana. DSTs collected 2,286 adults from St. Augustine vs 316 adults from
      Tamana (p < 0.002), STs collected 1,480 and 220 adults, respectively (p < 0.01),
      and the ovitraps collected 2,735 and 517 eggs, respectively from St. Augustine
      and Tamana (p < 0.002). Based on these results, the DSTs collected significantly
      (P < 0.02) more adults than the STs. The DSTs and STs collected both adult and
      immature stages which can be used for toxicology, virology, and PCR studies and
      are suitable alternative Ae. aegypti surveillance tools for the Caribbean and
      Latin American region.

PMID- 21175948
TI  - Mosquito fauna inhabiting water bodies in the urban environment of Cordoba city,
      Argentina, following a St. Louis encephalitis outbreak.
AB  - An understanding of urban aquatic environments as mosquito larval habitats is
      necessary to prioritize sites for surveillance and control of arbovirus vectors
      in urban areas. Natural and artificial water bodies at ground level that may be
      larval mosquito habitats in Cordoba city, Argentina were surveyed. Data on the
      characteristics of aquatic sites and the presence and abundance of mosquito
      larvae and pupae were collected in the summer of 2006, coinciding with the first
      report of human WNV and following an outbreak of St. Louis encephalitis in 2005.
      Eight species in the genera Aedes, Culex, and Mansonia were identified. At 64.2%
      (34 of 53) of the sites, only one species was collected, while 3.8% (2 of 53) had
      three associated species, the highest richness found per site. Culex
      quinquefasciatus represented over 99% (out of 32,729) of the specimens. It was
      also the most widely distributed and detected under diverse habitat conditions.
      Although puddles and semi-permanent pools harbored a greater number of species,
      drainages and channels may be more relevant as risk factors from an
      epidemiological point of view because they showed the highest larval densities,
      mainly of Cx. quinquefasciatus (vector of SLE and WNV). Also, higher densities of
      this species were associated with stormwater runoff and sewage water, thus water
      management systems should be targeted and closely monitored for mosquito control
      purposes.

PMID- 21175949
TI  - IrML - a gene encoding a new member of the ML protein family from the hard tick,
      Ixodes ricinus.
AB  - Blood intake causes significant changes in ticks, triggering vital physiological
      processes including differential gene expression. A gene encoding Ixodes ricinus
      ML-domain containing protein (IrML) is one of the set of the genes that are
      strongly induced by blood meals. IrML belongs to the ML protein family that
      commonly occurs in diverse organisms and is involved in lipid binding and
      transport, pathogen recognition or in immune response. An IrML gene was amplified
      from cDNA of engorged I. ricinus females using the gene-specific primers designed
      on a basis of partial sequences of related genes for ML domain protein. IrML was
      shown to be expressed mainly in the gut, but also in salivary glands and
      hemolymph of all tick developmental stages. Using in situ hybridization, IrML
      transcripts were detected in type II and III salivary glands acini. Analysis of
      the predicted structure of I. ricinus ML-domain containing protein and its
      localization in the tick body could suggest that IrML is a secreted protein and
      is possibly involved in tick innate immunity.

PMID- 21175950
TI  - Influence of competing and predatory invertebrate taxa on larval populations of
      mosquitoes in temporary ponds of wetland areas in Germany.
AB  - Abundances of mosquito larvae and associated invertebrate communities were
      assessed in 27 temporary ponds during the spring season in wetland areas of
      Germany. Four genera of mosquitoes were identified: Aedes, Anopheles, Culex, and
      Culiseta. We focused our analyses on Aedes spp. because this genus was the most
      abundant (92% of total abundance) and frequently encountered mosquito (present in
      65% of investigated sites). The abundance of Aedes spp. was negatively associated
      with the abundance of competitors for food, and to a lesser extent with those of
      intraguild predators and strict predators. The influence of these natural
      antagonists on larvae of Aedes was stronger in ponds with higher levels of
      dissolved oxygen (53 +/- 4%) than in ponds with lower levels (16 +/- 1%). The
      overall abundance of antagonists explained 42% of the variation in abundance of
      Aedes spp. at sites with higher levels of dissolved oxygen. Of this explained
      variation, competitors accounted for 34.7%, whereas the abundance of intraguild
      predators and strict predators accounted for only 6.8 and 0.5%, respectively.
      Therefore, the promotion of competing species might be an appropriate ecological
      approach for the control of Aedes spp. in temporary ponds in these areas.

PMID- 21175951
TI  - An improved experimental hut design for the study of Aedes aegypti (Diptera:
      Culicidae) movement patterns in Thailand.

PMID- 21175952
TI  - Update on the distribution of Triatoma bolivari and Triatoma brailovskyi
      (Hemiptera: Reduviidae: Triatominae) in western Mexico.

PMID- 21175953
TI  - A comparison of visual and flagging methods for estimating adult Ixodes pacificus
      (Acari: Ixodidae) tick abundance.

PMID- 21175954
TI  - Vector competence of Florida mosquitoes for chikungunya virus.

PMID- 21175956
TI  - Rectal swab sampling followed by an enrichment culture-based real-time PCR assay
      to detect Salmonella enterocolitis in children.
AB  - Although routine bacterial culture is the traditional reference standard method
      for the detection of Salmonella infection in children with diarrhoea, it is a
      time-consuming procedure that usually only gives results after 3-4 days. Some
      molecular detection methods can improve the turn-around time to within 24 h, but
      these methods are not applied directly from stool or rectal swab specimens as
      routine diagnostic methods for the detection of gastrointestinal pathogens. In
      this study, we tested the feasibility of a bacterial enrichment culture-based
      real-time PCR assay method for detecting and screening for diarrhoea in children
      caused by Salmonella. Our results showed that the minimum real-time PCR assay
      time required to detect enriched bacterial culture from a swab was 3 h. In all
      children with suspected Salmonella diarrhoea, the enrichment culture-based real
      time PCR achieved 85.4% sensitivity and 98.1% specificity, as compared with the
      53.7% sensitivity and 100% specificity of detection with the routine bacterial
      culture method. We suggest that rectal swab sampling followed by enrichment
      culture-based real-time PCR is suitable as a rapid method for detecting and
      screening for Salmonella in paediatric patients.

PMID- 21175955
TI  - Retrospective audit of the air-Q intubating laryngeal airway as a conduit for
      tracheal intubation in pediatric patients with a difficult airway.
AB  - OBJECTIVES: To assess the efficacy of the ILA as a conduit for tracheal
      intubation in pediatric patients with a difficult airway. AIM: The primary goals
      of this retrospective audit were to assess the clinical performance of the ILA in
      pediatric patients with a difficult airway, expand on our initial favorable
      experience with this device, and collect pilot data for future prospective and
      comparison studies. METHODS: The charts of patients with a difficult airway in
      whom the ILA was used during a period of 1 year in a freestanding pediatric
      institution were reviewed following a practice change in the authors' institution
      favoring the ILA over the laryngeal mask airway as a conduit for tracheal
      intubation. RESULTS: Thirty-four pediatric patients had an ILA placed during the
      course of their airway management. Eight of the 34 patients in this cohort
      required emergent airway management. The median age was 47.1 (0.3-202.2) months
      and the median weight was 16.3 (3.9-86.0) kilograms. Three of the cases were
      unanticipated difficult airways and the remaining were anticipated difficult
      airways as a result of craniofacial syndromes (n = 21), cervical spine
      instability or immobility (n = 7), or airway hemorrhage (n = 3). Thirty-three of
      the 34 patients (97%) were intubated on the first attempt through the ILA, with
      the aid of a fiberoptic bronchoscope (n = 25), a Shikani Optical Stylet (n = 7),
      or blindly (n = 2). In one patient, blind tracheal intubation required a second
      attempt for successful intubation, making the overall success rate 100%. Oxygen
      desaturation was noted in 6 of the 34 cases. CONCLUSIONS: In a series of
      pediatric patients with difficult airways, the ILA was successfully used as a
      conduit for tracheal intubation in all patients. Visualization techniques may
      offer a greater degree of success in intubations through the ILA due to the
      potential for epiglottic down-folding in children.

PMID- 21175957
TI  - The socio-ecology of zoonotic infections.
AB  - The resurgence of infectious diseases of zoonotic origin observed in recent years
      imposes a major morbidity/mortality burden worldwide, and also a major economic
      burden that extends beyond pure medical costs. The resurgence and epidemiology of
      zoonoses are complex and dynamic, being influenced by varying parameters that can
      roughly be categorized as human-related, pathogen-related, and
      climate/environment-related; however, there is significant interplay between
      these factors. Human-related factors include modern life trends such as
      ecotourism, increased exposure through hunting or pet owning, and culinary
      habits, industrialization sequelae such as farming/food chain intensification,
      globalization of trade, human intrusion into ecosystems and urbanization,
      significant alterations in political regimes, conflict with accompanying
      breakdown of public health and surveillance infrastructure, voluntary or
      involuntary immigration, loosening of border controls, and hierarchy issues in
      related decision-making, and scientific advances that allow easier detection of
      zoonotic infections and evolution of novel susceptible immunocompromised
      populations. Pathogen-related factors include alterations in ecosystems and
      biodiversity that influence local fauna synthesis, favouring expansion of disease
      hosts or vectors, pressure for virulence/resistance selection, and genomic
      variability. Climate/environment-related factors, either localized or extended,
      such as El Nino southern oscillation or global warming, may affect host-vector
      life cycles through varying mechanisms. Emerging issues needing clarification
      include the development of predictive models for the infectious disease impact of
      environmental projects, awareness of the risk imposed on immunocompromised
      populations, recognition of the chronicity burden for certain zoonoses, and the
      development of different evaluations of the overall stress imposed by a zoonotic
      infection on a household, and not strictly a person.

PMID- 21175958
TI  - How many patients do we need for a clinical trial? Demystifying sample size
      calculations.
AB  - Determining the number of subjects required for a study is a critical component
      when planning a research project. An adequate number of patients are needed in
      order to be able to answer the research question of interest with a degree of
      certainty. In this paper, the information that is required for determining the
      sample size is described. The primary aim is to demystify the sample size section
      in published clinical trials. Some of the difficulties in determining the sample
      size correctly are also highlighted and some good practices recommended.

PMID- 21175959
TI  - How to conduct a randomized trial.
AB  - Randomized controlled clinical trials represent the gold standard of research
      into health-care interventions but conducting a randomized trial requires careful
      planning, structures and procedures. The conduct of a clinical trial is a
      collaborative effort between investigators, participants and a range of
      professionals involved both centrally and locally in the coordination and
      execution of the study. In this article, the key steps to conducting a randomized
      controlled trial are summarized.

PMID- 21175960
TI  - Characteristics of immunoglobulin A nephropathy with mesangial immunoglobulin G
      and immunoglobulin M deposition.
AB  - AIM: There are immunoglobulin (Ig)A nephropathy (IgAN) cases showing mesangial
      IgG and/or IgM deposition, however, their characteristics have remained unknown.
      METHODS: Three hundred and eighty-four IgAN patients were divided according to
      the existence of mesangial IgG and/or IgM deposition: IgA deposition only (A
      group, n = 77); IgA and IgM deposition (AM group, n = 114); IgA and IgG
      deposition (AG group, n = 36); and IgA, IgG and IgM deposition (AGM group, n =
      157). Clinical and histological findings, and outcomes were examined and compared
      among these four groups. RESULTS: At the time of renal biopsy, serum creatinine
      was significantly higher in the A and AM group, however, creatinine clearance did
      not differ among the four groups. The ratio of glomerular obsolescence was
      significantly higher in the AM group than in the A and AGM group, and the ratio
      of glomerular tuft adhesion was significantly higher in the AM, AG and AGM group
      than in the A group. However, the other clinical and histological findings,
      electron microscopic findings and renal survivals did not differ among the four
      groups. Proteinuria was independently associated with an increase in risk of
      doubling of creatinine (P = 0.005), however, IgG and IgM depositions were not by
      multivariate Cox regression. CONCLUSION: The presence of other Ig classes,
      besides IgA deposits, was found to be associated with glomerular obsolescence and
      tuft adhesions, however, without any effect on renal survival in IgAN.

PMID- 21175961
TI  - Thiol levels, protein carbonylation and anaerobic sulfur metabolism in
      erythrocytes of peritoneal dialysis and predialysis patients.
AB  - AIM: The goal of the present study was to investigate the changes in sulfur
      metabolism in erythrocytes of end-stage renal failure patients. METHODS:   The
      following substances were determined in erythrocytes of chronic kidney disease
      patients before dialysis, patients treated with continuous ambulatory peritoneal
      dialysis, and in a group of healthy volunteers: (i) sulfane sulfur level and
      activity of the enzymes involved in its metabolism and in cyanide detoxification;
      (ii) concentration of total and non-protein sulfhydryl groups -SH; and (iii)
      protein carbonylation rate. RESULTS:   Erythrocytes of chronic kidney disease
      patients in predialysis period contained lower levels of sulfane sulfur, non
      protein thiols, total thiols and 3-mercaptopyruvate sulfotransferase. On the
      other hand, in erythrocytes of end-stage renal failure patients treated with
      continuous ambulatory peritoneal dialysis, sulfane sulfur, non-protein thiols,
      total thiols and 3-mercaptopyruvate sulfotransferase activity remained at the
      level observed in healthy controls. These changes indicate a disturbed thiol
      balance and anaerobic cysteine metabolism in non-dialysis patients, whereas
      continuous ambulatory peritoneal dialysis patients did not show these disorders.
      gamma-Cystathionase activity was equally elevated in predialysis period and in
      peritoneal dialysis patients, which means that chronic kidney disease pathology
      is accompanied by an increased expression of this enzymatic activity in
      erythrocytes. Erythrocytic rhodanese activity was unchanged and stayed at the
      control level in both groups. Protein carbonylation rate was equally enhanced in
      both patient groups, which indicated acceleration of oxidative processes and
      inability of continuous ambulatory peritoneal dialysis to correct these changes
      in erythrocytes. CONCLUSION: The CAPD as a replacement therapy helps to preserve
      thiol levels and anaerobic sulfur metabolism in erythrocytes.

PMID- 21175962
TI  - Benefit and cost from the long-term use of cyclosporine-A in idiopathic
      membranous nephropathy.
AB  - AIM: Idiopathic membranous nephropathy (IMN), the most common cause of nephrotic
      syndrome in adults, is usually treated by cyclosporin A (CsA). Estimation of the
      effectiveness of long-term use of CsA in the remission and relapse rate of
      nephrotic syndrome along with histological changes in repeat renal biopsies was
      the aim of the study. METHODS: Thirty-two nephrotic patients with well-preserved
      renal function treated by prednisolone and CsA were studied. A repeat biopsy was
      performed in 18 patients with remission of nephrotic syndrome, after 24 months of
      treatment, to estimate the activity of the disease and features of CsA toxicity.
      RESULTS: Complete remission of nephrotic syndrome was observed in 18 (56%) and
      partial remission in 10 patients (31%) after 12 months of treatment (total 87%).
      Relapses were observed in 39% and 60% of patients with complete and partial
      remission, respectively, and multiple relapses in 25% of patients, who showed
      gradual unresponsiveness to CsA and decline of renal function. Progression of
      stage of the disease and more severe glomerulosclerosis and tubulointerstitial
      injury were recognized in 55% and 61% of patients respectively. Features of CsA
      nephrotoxicity were not observed. The severity of histological changes was
      related to the time elapsed from the first biopsy (r = 0.452, P < 0.05).
      CONCLUSION: Low doses of CsA with prednisolone induce remission of nephrotic
      syndrome in most idiopathic membranous nephropathy patients. Although typical
      features of CsA nephrotoxicity are not observed, significant deterioration of
      histological lesions occurs with time, even in patients with remission. Long-term
      use of CsA should be examined with caution.

PMID- 21175963
TI  - Clinical usefulness of serum cystatin C and the pertinent estimation of
      glomerular filtration rate based on cystatin C.
AB  - AIM: Although cystatin C has been developed as an alternative marker for
      estimating glomerular filtration rate (GFR), its clinical use is as yet limited.
      The significance of cystatin C for differentiating chronic kidney disease (CKD)
      stages and established cystatin C-based equations estimating GFR were evaluated.
      METHODS: The fresh frozen serum samples from CKD (n = 119) and healthy volunteers
      (n = 22) were evaluated. Serum creatinine (sCr) was measured by the kinetic Jaffe
      method, and recalibrated to the isotope dilution mass spectrometry (IDMS).
      Cystatin C was measured using a particle-enhanced nephelometric assay. RESULTS:
      CKD stages were more sensitively differentiated by cystatin C compared to sCr,
      especially in moderate and severe kidney dysfunction. Sex and body mass index did
      not affect cystatin C level. Pearson's correlation coefficients of reciprocal of
      cystatin C, measured and recalibrated sCr compared to systemic inulin clearance
      (Cl(in) ) were 0.757, 0.734 and 0.709, respectively. We derived novel pertinent
      equations based on cystatin C (model 1: 1.404 * cystatin C(-0.895)  * age(0.006)
      * weight(1.074) * height(-1.562)  * (0.865; if female); model 2: 43.287 *
      cystatin C(-0.906) * age(0.101) * (0.762; if female)]. Models 1 and 2 showed
      superior performance in representing systemic Cl(in) than the IDMS Modification
      of Diet in Renal Disease (MDRD) study equations did (adjusted r(2) = 0.76 and
      0.72 for models 1 and 2, and 0.64 and 0.65 for 4 and 6 variable IDMS MDRD
      equations, respectively). CONCLUSION:   Cystatin C reflects kidney dysfunction
      sensitively, and thus cystatin C-based estimation of GFR could provide a reliable
      support for clinical practice.

PMID- 21175964
TI  - Multiple intercostal neurofibromas in a patient with autosomal dominant
      polycystic kidney disease.

PMID- 21175965
TI  - A candidate kidney donor with anatomic variations in renal arteries.

PMID- 21175966
TI  - Unilateral upper limb lympatic obstruction and severe lymphoedema in a patient on
      long-term sirolimus.

PMID- 21175967
TI  - Delayed great-vessel perforation related to an indwelling haemodialysis catheter
      over the left internal jugular vein.

PMID- 21175968
TI  - Influenza A H1N1, microscopic polyangiitis and pulmonary haemorrhage.

PMID- 21175970
TI  - Renal palliative care in Australia: time to engage.

PMID- 21175971
TI  - Palliative care in end-stage kidney disease.
AB  - Patients with end-stage kidney disease have significantly increased morbidity and
      mortality. While greater attention has been focused on advanced care planning,
      end-of-life decisions, conservative therapy and withdrawal from dialysis these
      must be supported by adequate palliative care incorporating symptom control. With
      the increase in the elderly, with their inherent comorbidities, accepted onto
      dialysis, patients, their nephrologists, families and multidisciplinary teams,
      are often faced with end-of-life decisions and the provision of palliative care.
      While dialysis may offer a better quality and quantity of life compared with
      conservative management, this may not always be the case; hence the patient is
      entitled to be well-informed of all options and potential outcomes before
      embarking on such therapy. They should be assured of adequate symptom control and
      palliative care whichever option is selected. No randomized controlled trials
      have been conducted in this area and only a small number of observational studies
      provide guidance; thus predicting which patients will have poor outcomes is
      problematic. Those undertaking dialysis may benefit from being fully aware of
      their choices between active and conservative treatment should their functional
      status seriously deteriorate and this should be shared with caregivers. This
      clarifies treatment pathways and reduces the ambiguity surrounding decision
      making. If conservative therapy or withdrawal from dialysis is chosen, each
      should be supported by palliative care. The objective of this review is to
      summarize published studies and evidence-based guidelines, core curricula,
      position statements, standards and tools in palliative care in end-stage kidney
      disease.

PMID- 21175972
TI  - Intra-dialytic hypotension and blood volume and blood temperature monitoring.
AB  - Intra-dialytic hypotension (IDH) is a common problem affecting haemodialysis
      patients. Its aetiology is complex and influenced by multiple patient and
      dialysis factors. IDH occurs when the normal cardiovascular response cannot
      compensate for volume loss associated with ultrafiltration, and is exacerbated by
      a myriad of factors including intra-dialytic fluid gains, cardiovascular disease,
      antihypertensive medications and the physiological demands placed on patients by
      conventional haemodialysis. The use of blood volume monitoring and blood
      temperature monitoring technologies is advocated as a tool to predict and
      therefore prevent episodes of IDH. We review the clinical utility of these
      technologies and summarize the current evidence of their effect on reducing the
      incidence of IDH in haemodialysis population.

PMID- 21175973
TI  - Peritoneal dialysis practice in Australia and New Zealand: a call to action.
AB  - Peritoneal dialysis technique survival in Australia and New Zealand is lower than
      in other parts of the world. More than two-thirds of technique failures are
      related to infective complications (predominantly peritonitis) and 'social
      reasons'. Practice patterns vary widely and more than one-third of peritoneal
      dialysis units do not meet the International Society of Peritoneal Dialysis
      minimum accepted peritonitis rate. In many cases, poor peritonitis outcomes
      reflect significant deviations from international guidelines. In this paper we
      propose a series of practical recommendations to improve outcomes in peritoneal
      dialysis patients through appropriate patient selection, prophylaxis and
      treatment of infectious complications, investigation of social causes of
      technique failure and a greater focus on patient education and clinical
      governance.

PMID- 21175974
TI  - Adriamycin nephropathy: a model of focal segmental glomerulosclerosis.
AB  - Adriamycin nephropathy (AN) is a rodent model of chronic kidney disease that has
      been studied extensively and has enabled a greater understanding of the processes
      underlying the progression of chronic proteinuric renal disease. AN is
      characterized by podocyte injury followed by glomerulosclerosis,
      tubulointerstitial inflammation and fibrosis. Genetic studies have demonstrated a
      number of loci that alter both risk and severity of renal injury induced by
      Adriamycin. Adriamycin-induced renal injury has been shown in numerous studies to
      be modulated by both non-immune and immune factors, and has facilitated further
      study of mechanisms of tubulointerstitial injury. This review will outline the
      pharmacological behaviour of Adriamycin, and describe in detail the model of AN,
      including its key structural characteristics, genetic susceptibility and
      pathogenesis.

PMID- 21175975
TI  - Acute dialysis in HIV-positive patients in Cape Town, South Africa.
AB  - AIM: The prognosis for HIV patients needing acute dialysis is uncertain. The aim
      of this study was to describe the clinical presentation, renal diagnoses and
      outcomes of HIV patients who underwent acute haemodialysis at Groote Schuur
      Hospital in the period 2002-2007. METHODS: A retrospective review of case records
      of HIV patients who underwent acute haemodialysis was conducted. RESULTS: One
      hundred and seventeen patients were reviewed (median age 34.0 years (29.0-40.0)
      53.8% men, 93.2% black Africans) and 33 had a renal biopsy. Acute tubular
      necrosis (ATN) was diagnosed in 68 patients. Recovery of renal function occurred
      in 33.3% of all patients while in 25.7% treatment was withdrawn and 41.0% died in
      hospital. Suspected ATN was the commonest cause of renal disease in those who
      recovered renal function (82.1%). A higher CD4 count (odds ratio (OR)=0.994,
      P=0.007), lower pre-dialysis serum creatinine (<1230 umol/L) and longer
      hospitalization (OR=0.93, P=0.006) significantly correlated with survival.
      CONCLUSION: There is a good chance of survival for HIV patients needing acute
      dialysis when the diagnosis is ATN, and when the CD4 count is more than 200
      cells/mm3.

PMID- 21175976
TI  - The advent of interventional nephrology.

PMID- 21175977
TI  - Percutaneous maintenance and salvage of dysfunctional arteriovenous fistulae and
      grafts by nephrologists in Australia.
AB  - AIM: Percutaneous endovascular procedures can maintain and salvage dysfunctional
      arteriovenous fistulae and grafts used in haemodialysis. The aim of this study is
      to report the experience of nephrologists from a single centre in Australia with
      these procedures. METHODS: A total of 187 consecutive percutaneous vascular
      procedures (angioplasty, angioplasty+/-thrombolysis, stent placement and
      accessory vein ligation) were performed in 100 haemodialysis patients with
      dysfunctional arteriovenous fistulae and grafts between January 2006 and July
      2009 in a single centre. All relevant clinical and radiological data collected
      during this period were reviewed retrospectively. Post patency rates were
      estimated using the Kaplan-Meier method. RESULTS: The clinical and anatomic
      success rates were 93% (172 of 184 interventions) and 91% (169 of 184
      interventions), respectively. The overall complication rate was 5.9%. A major
      complication leading to access loss occurred in one patient (0.5%). The primary
      patency rates at 6, 12 and 18 months were 72%, 55% and 47%, respectively. The
      secondary patency rates at 6, 12 and 18 months were 96%, 93% and 90%,
      respectively. The mean cumulative patency was 36.8 months+/-SE 1.27 (95%CI 36.8
      39.3). The mean fluoroscopy screening time was 11.5+/-8.5 min. CONCLUSION: This
      study demonstrates that high anatomic success and excellent patency rates can be
      obtained with percutaneous endovascular procedures and that appropriately trained
      interventional nephrologists can perform these procedures safely and effectively.

PMID- 21175978
TI  - Increasing home based dialysis therapies to tackle dialysis burden around the
      world: a position statement on dialysis economics from the 2nd Congress of the
      International Society for Hemodialysis.

PMID- 21175979
TI  - One year experience of nocturnal home haemodialysis with an alternate night
      schedule in Hong Kong.
AB  - AIM: Nocturnal home haemodialysis (NHHD) was started in Hong Kong in 2006. The
      experience of 1 year of NHHD with an alternate night schedule in two local
      centres is reported. METHODS: The clinical parameters of 14 patients who had
      completed 1 year of NHHD were retrospectively analyzed. All patients were
      receiving an alternate night schedule (3.5 sessions/week) for 6-8 h/session.
      RESULTS: After 1 year of NHHD, haemoglobin levels increased from 9.6+/-1.6 g/dL
      before NHHD to 11.4+/-2.2 g/dL (P<0.05) despite a reduction in erythropoietin
      dose requirement from 120.6+/-44.3 to 59.4+/-74.6 U/kg/week (P<0.05). Four
      patients (29%) were able to stop taking erythropoietin after NHHD. Serum
      phosphate levels reduced from 2.33+/-0.41 to 1.59+/-0.29 mmol/L (P<0.01) and
      calcium phosphate product decreased from 5.29+/-0.96 to 3.74+/-0.90 mmol2/L2
      (P<0.01). Phosphate binder dose was greatly reduced and eight patients (67%) were
      able to stop taking phosphate binders. The number of antihypertensive medications
      tended to reduced from 2.5+/-1.3 to 1.6+/-1.5 (P=0.067) with four patients (29%)
      able to stop antihypertensives. Left ventricular mass index decreased from 186+/
      62 to 168+/-60 g/m2 (P=0.463) although this was not statistically significant.
      Weekly spKt/V during conventional haemodialysis was 3.63+/-0.95 while that during
      NHHD was three times higher at 11.09+/-6.44 (P<0.01). The quality of life indexes
      also showed improvement. CONCLUSION: This 1 year experience of alternate night
      NHHD demonstrates benefits in terms of anaemia control, erythropoietin
      requirement, serum phosphate and calcium phosphate product reduction, blood
      pressure control, haemodialysis adequacy and quality of life. NHHD with an
      alternate night schedule is a promising dialytic therapy for patients receiving
      chronic haemodialysis in this locality.

PMID- 21175980
TI  - Epidemiology of culture isolates from peritoneal dialysis peritonitis patients in
      southern India using an automated blood culture system to culture peritoneal
      dialysate.
AB  - AIM: Continuous ambulatory peritoneal dialysis (CAPD) is a major form of therapy
      for chronic end stage renal disease patients, which may lead to CAPD-associated
      peritonitis. The spectrum of organisms associated with CAPD peritonitis varies
      geographically. Not much data is available regarding this from southern India.
      The aim of this study was to characterize the spectrum of organisms associated
      with CAPD peritonitis in this region and observe the utility of automated blood
      culture systems to culture peritoneal dialysate. METHODS: Ninety episodes of
      peritonitis were cultured over a span of 3 years using an automated blood culture
      system. RESULTS: The yield of culture positivity was 50%. The most predominant
      organism was found to be coagulase-negative Staphylococcus spp. (21.1%) followed
      by Enterobacteriaceae (12.2%). Other organisms isolated were non-fermenting Gram
      negative bacilli (4.4%), Pseudomonas aeruginosa (3.3%), alpha-haemolytic
      Streptococci (3.3%), Candida spp. (2.2%), Staphylococcus aureus (1.1%), beta
      haemolytic Streptococci (1.1%) and Micrococci (1.1%). A high degree of resistance
      to third generation cephalosporins (66.7%) was noted amongst the Gram-negative
      bacilli. Also, all the Gram-negative bacilli isolated from patients who had prior
      empirical antibiotic therapy of ceftazidime before arrival at the centre, were
      resistant to third generation cephalosporins. CONCLUSION: A varied spectrum of
      organisms isolated from peritoneal dialysate compared to the global scenario was
      observed. Also, a high degree of third generation cephalosporin resistance was
      noted amongst the Gram-negative bacilli. Thus, it is suggested that the empirical
      therapy should be dependent on the local epidemiology.

PMID- 21175981
TI  - Anti-inflammatory effect of an insulin infusion in patients on maintenance
      haemodialysis: a randomized controlled pilot study.
AB  - AIM: A pilot study to investigate the anti-inflammatory effect of insulin in
      patients on maintenance haemodialysis. BACKGROUND: Elevated concentrations of pro
      inflammatory and oxidative mediators are thought to contribute to the increased
      cardiovascular risk in haemodialysis. Insulin has been demonstrated to have anti
      inflammatory properties and a continuous low-dose insulin infusion in critically
      ill patients is associated with improved outcomes. The anti-inflammatory effects
      of insulin in haemodialysis have not been investigated. METHODS: In a single
      blind cross-over study, 11 stable, non-diabetic, haemodialysis patients received
      a continuous insulin infusion (Actrapid 2 IU/h) during a dialysis of 4 h or a
      conventional dialysis in random order. Normoglycaemia was maintained by a
      modified glucose dialysate and glucose infusion. Blood samples were collected at
      baseline, 1, 4, 6 and 24 h. C-reactive protein (CRP), tumour necrosis factor
      alpha, interleukin-6, neopterin, vascular cell adhesion molecule 1, protein
      thiols, dityrosine and peroxides were measured. RESULTS: Insulin produced a
      significant reduction in median CRP over the immediate dialysis phase (confidence
      interval) by 6% (2-9% (95% CI), P=0.006) and an even greater decline at 24 h (19%
      (8-28%, 95% CI), P=0.001) compared with values of the conventional dialysis. No
      significant changes were observed in the other markers. Median glucose levels
      were comparable during both dialysis sessions. CONCLUSIONS: During haemodialysis,
      insulin may have a modest anti-inflammatory effect as evident by a reduction in
      CRP that appears to have a persistent effect over the next 24 h post dialysis.
      More studies are required to examine longer-term benefits as well as the
      potential role in more high-risk individuals.

PMID- 21175982
TI  - Effects of proteasome inhibitors on rat renal fibrosis in vitro and in vivo.
AB  - AIM: Transforming growth factor-beta (TGF-beta) is involved in renal
      tubulointerstitial fibrosis. Recently, the ubiquitin proteasome system was shown
      to participate in the TGF-beta signalling pathway. The aim of this study was to
      examine the effects of proteasome inhibitors on TGF-beta-induced transformation
      of renal fibroblasts and tubular epithelial cells in vitro and on unilateral
      ureteral obstruction (UUO) in vivo. METHODS: Rat renal fibroblasts NRK-49F cells
      and tubular epithelial cells, NRK-52E, were treated with TGF-beta in the presence
      or absence of a proteasome inhibitor, MG132 or lactacystin. Rats were subjected
      to UUO and received MG132 i.p. for 7 days. RESULTS: In cultured renal cells, both
      MG132 and lactacystin inhibited TGF-beta-induced alpha-smooth muscle actin (alpha
      SMA) protein expression according to both western blotting and immunofluorescent
      study results. MG132 also suppressed TGF-beta-induced mRNA expression of alpha
      SMA and upregulation of Smad-response element reporter activity. However, MG132
      did not inhibit TGF-beta-induced phosphorylation and nuclear translocation of
      Smad2. In contrast, MG132 increased the protein level of Smad co-repressor SnoN,
      demonstrating that SnoN is one of the target molecules by which MG132 blocks the
      TGF-beta signalling pathway. Although the proteasome inhibitor suppressed TGF
      beta-induced transformation of cultured fibroblasts and tubular epithelial cells,
      MG132 treatment did not ameliorate tubulointerstitial fibrosis in the rat UUO
      model. CONCLUSION: Proteasome inhibitors attenuate TGF-beta signalling by
      blocking Smad signal transduction in vitro, but do not inhibit renal interstitial
      fibrosis in vivo.

PMID- 21175983
TI  - Pattern of renal diseases observed in native renal biopsies in adults in a single
      centre in Pakistan.
AB  - AIM: In the absence of a national renal biopsy registry, there is a paucity of
      information on the pattern of renal disease observed in native renal biopsies in
      adults in Pakistan. METHODS: A retrospective review of native renal biopsies
      performed in adult patients was undertaken at the Sindh Institute of Urology and
      Transplantation (SIUT) during the period from July 1995 to December 2008. Renal
      biopsies were studied by light, immunofluorescence and electron microscopy. The
      renal biopsy diagnoses were categorized into the following groups:
      glomerulopathies (GN), tubulointerstitial diseases (TID), renal vascular diseases
      (VD), and hereditary diseases (HD). RESULTS: A total of 1793 adult patients were
      included in the study. GN was the commonest diagnosis representing 83.9% of all
      biopsies. Primary GN (PGN) accounted for 86.9% and secondary GN (SGN) for 13%.
      When PGN was further analyzed, focal segmental glomerulosclerosis (FSGS) was the
      leading histopathological diagnosis, found in 29% of PGN, followed by membranous
      GN (MGN), seen in 23.5% of cases. Among SGN, lupus nephritis (44.1%) was the
      commonest, followed by amyloidosis (42.1%) and diabetic nephropathy (8.1%). TID
      comprised 11.6% of all renal biopsy diagnoses. VD and HD were less frequent,
      found in 3.9% and 0.4%, respectively. CONCLUSION: The pattern of biopsied renal
      pathology is similar to that reported recently from other parts of the world with
      similar biopsy indications.

PMID- 21175984
TI  - Cut-off values for serum matrix metalloproteinase-9: is there a threshold to
      predict renal involvement for Henoch-Schonlein purpura in children?
AB  - AIM: To clarify whether the level of matrix metalloproteinase-9 (MMP-9), tissue
      inhibitor matrix metalloproteinase-1 (TIMP-1) or the ratio of MMP-9/TIMP-1 was
      associated with the renal involvement in Henoch-Schonlein purpura (HSP); and to
      explore whether there existed early diagnostic measure for HSP nephritis (HSPN).
      METHODS: Sixty-six patients with HSPN, 68 patients with HSP and 60 healthy
      children (control group) were enrolled into our study. Serum and urine samples
      before treatment were collected for detection. RESULTS: Compared with the HSP
      group and control group, serum MMP-9, TIMP-1 and ratio of MMP-9/TIMP-1 in the
      HSPN group were significantly higher (P<0.05 and P<0.01, respectively). Urine MMP
      9, TIMP-1 and ratio of MMP-9/TIMP-1 in the HSPN group were obviously higher than
      those of the control group (P<0.05) and the HSP group (P<0.05). Receiver-operator
      curve (ROC) analysis was performed to obtain the area under the curve (AUC) and
      the AUC and its 95% confidence interval (CI) of serum MMP-9 were 0.97 and 0.95
      0.99, respectively. The optimal cut-off point (sensitivity; specificity) of serum
      MMP-9 for diagnosing HSPN was 179.79 mg/L (0.96; 0.88). CONCLUSION: Levels of MMP
      9, TIMP-1 and ratio of MMP-9/TIMP-1 in serum and urine were remarkably high in
      the patients with HSPN, but the serum MMP-9 was more sensitive. Serum MMP-9 may
      be associated with the occurrence and development of renal involvement in HSPN
      and become an important indicator for early diagnosis of HSPN.

PMID- 21175985
TI  - Renal biopsy in type 2 diabetes: timing of complications and evaluating of safety
      in Chinese patients.
AB  - AIM: It has been recognized that renal lesions in patients with diabetes often
      have other causes of renal damage concomitantly. Renal biopsy is a valuable tool
      to provide histological evidence. However, the safety in patients with type 2
      diabetes receiving renal biopsy is not well evaluated. This study was conducted
      to monitor the dynamic complications and to evaluate the safety of biopsy in
      diabetic patients. METHODS: A prospective observation was performed on 130
      patients with type 2 diabetes and 150 patients not undergoing renal biopsy. The
      complications were monitored at 4 h, 8 h, 24 h, 48 h and 72 h sequentially after
      biopsy. RESULTS: Haematoma was observed in 34 (26.15%) patients with diabetes and
      50 (33.33%) in controls (P=0.19). The timing of large haematoma peaked at 4 h.
      Gross haematuria occurred in 12 (9.23%) diabetic patients and eight (5.33%)
      controls (P=0.207). It happened mainly within 8 h. Renal pathological diagnosis
      showed 96 (73.85%) cases with diabetic nephropathy and 34 (26.15%) cases with non
      diabetic renal disease. CONCLUSION: Renal biopsy in patients with type 2 diabetes
      is safe. The frequency of complications after renal biopsy in diabetes is no
      higher than those without diabetes. The complications mostly happened within 8 h,
      especially within 4 h. Biopsy is also very necessary to rule out other chronic
      renal diseases in diabetes.

PMID- 21175986
TI  - Translation, cultural adaptation assessment, and both validity and reliability
      testing of the Kidney Disease Quality of Life--Short Form version 1.3 for use
      with Iranian patients.
AB  - AIM: The aims of the study were to translate the Kidney Disease Quality of Life-
      Short Form version 1.3 (KDQOL-SF ver. 1.3) questionnaire into Iranian (Farsi),
      and to then assess it in terms of validity and reliability on Iranian patients.
      METHODS: The questionnaire was first translated into Farsi by two independent
      translators, and then subsequently translated back into English. After
      translation disparities had been reconciled, the final Iranian questionnaire was
      tested. An initial test-retest reliability evaluation was performed over a 10 day
      period on a sample of 20 patients recruited from a larger group (212 patients
      with end-stage renal disease on haemodialysis). Afterwards, reliability was
      estimated by internal consistency, and validity was assessed using known group
      comparisons and constructs for the patient group as a whole. Finally, the factor
      structure of the questionnaire was extracted by performing exploratory factor
      analysis. RESULTS: All of the scales in the questionnaire showed good test-retest
      reliability (i.e. intraclass correlations between test and retest scores were
      >0.7). All of the scales met the minimal criteria (0.7) for internal consistency
      and Cronbach's-alpha ranged 0.71-0.93. Furthermore, results from a discriminate
      validity evaluation showed that the questionnaire could be used to discriminate
      between subgroups of the patients. Finally, a principal component analysis of the
      disease-specific scales indicated that this part of the questionnaire could be
      summarized into an 11 factor structure that jointly accounted for 79.81% of the
      variance. CONCLUSION: The Iranian version of the KDQOL-SF questionnaire is both
      highly reliable and valid for use with Iranian patients on haemodialysis.

PMID- 21175987
TI  - Low-dose valaciclovir and cytomegalovirus immunoglobulin to prevent
      cytomegalovirus disease in high-risk renal transplant recipients.
AB  - BACKGROUND: Cytomegalovirus (CMV) remains an important cause of disease in renal
      transplant recipients. Prophylaxis is effective in reducing disease; however, the
      optimal regimen remains uncertain. We assessed the efficacy of low-dose
      valaciclovir (3 months) and intravenous CMV immunoglobulin in the prevention of
      CMV disease in CMV-negative recipients of kidneys from CMV-positive donors (D+/R
      ). METHODS: A single-centre, retrospective study examining the incidence of CMV
      disease and patient and graft survival in all patients transplanted between
      October 2000 and November 2004. RESULTS: Among 203 renal transplant recipients,
      46 were D+/R- (22.7%) and received prophylaxis. Of the 203 recipients, 21 (10.3%)
      developed CMV disease over a four-year follow-up period. Within the D+/R- group,
      CMV disease occurred in 15.2% of patients at 6 months (7/46), and 21.7% at 4
      years (10/46). Of the 10 D+/R- patients who developed CMV disease, six were
      inadvertently on a dose of valaciclovir below that dictated by protocol arising
      from a failure to increase dosage in parallel with improving recipient renal
      function. In the D+/R- recipients where the protocol was adhered to, the
      incidence of CMV disease was 5% (2/40) at 6 months, and 10% (4/40) at 4 years.
      CONCLUSION: Low-dose valaciclovir with CMV immunoglobulin was as efficacious in
      preventing CMV disease as other published regimens, including those with full
      dose valaciclovir and valganciclovir. There was a low incidence of CMV disease
      beyond 6 months. Outcomes could be improved by ensuring appropriate dose
      adjustment following changes in renal function.

PMID- 21175988
TI  - Nutcracker syndrome.

PMID- 21175989
TI  - Prolonged survival in renal transplant recipient with advanced renal cell
      carcinoma by everolimus and sorafenib.

PMID- 21175990
TI  - Gas in the renal shadow of a plain abdominal X-ray: emphysematous pyelonephritis.

PMID- 21175991
TI  - Downregulation of Mus81 as a novel prognostic biomarker for patients with
      colorectal carcinoma.
AB  - The Mus81 gene encodes a critical endonuclease involved in DNA repair and tumor
      suppression. Our previous study has shown reduced expression of Mus81 in
      hepatocellular carcinoma and its association with the metastatic potential and
      prognosis of hepatocellular carcinoma. However, the role of Mus81 in colorectal
      carcinoma is currently unknown. We therefore carried out the present study to
      explore the correlation between Mus81 expression and the progression of
      colorectal carcinoma. Mus81 expression in 92 cases of colorectal carcinoma and
      matched normal tissues was determined by quantitative real-time polymerase chain
      reaction. Our results showed that Mus81 expression in colorectal carcinoma
      tissues was significantly reduced compared with the corresponding normal tissues
      (P < 0.001) and the downregulation of Mus81 (decreased by more than 50%) was
      found in 60.9% (56/92) of colorectal carcinoma. Moreover, Mus81 downregulation
      correlated significantly to hepatic metastasis (P = 0.019) and a high TNM stage
      (P = 0.025) of colorectal carcinoma. In addition, the decrease of Mus81 was also
      detected in 10 cases of hepatic metastasis tissues compared with the
      corresponding primary colorectal carcinoma tissues (P = 0.016). More importantly,
      colorectal carcinoma patients with apparent Mus81 downregulation have shown
      significantly poorer overall survival than those with little Mus81 downregulation
      (P = 0.0374). Also, multivariable Cox regression analysis identified Mus81
      downregulation as an independent prognostic factor for colorectal carcinoma
      (hazard ratio, 1.678; P = 0.040). In conclusion, the reduced expression of Mus81
      is closely related to hepatic metastasis and poor prognosis of colorectal
      carcinoma, indicating Mus81 as a novel prognostic marker for colorectal
      carcinoma.

PMID- 21175992
TI  - Phase II study of erlotinib plus gemcitabine in Japanese patients with
      unresectable pancreatic cancer.
AB  - Erlotinib combined with gemcitabine has not been evaluated in Japanese patients
      with unresectable pancreatic cancer. This two-step phase II study assessed the
      safety and pharmacokinetics of erlotinib 100 mg/day (oral) plus gemcitabine 1000
      mg/m(2) (i.v. days 1, 8, 15) in a 28-day cycle in the first step, and efficacy
      and safety in the second step. The primary end-point was safety. One hundred and
      seven patients were enrolled (first step, n = 6; second step, n = 101). The most
      common adverse event was RASH (compiled using the preferred terms rash, acne,
      exfoliative rash, dermatitis acneiform, erythema, eczema, dermatitis and pustular
      rash) in 93.4% of patients. One treatment-related death occurred. While
      interstitial lung disease-like events were reported in nine patients (8.5%; grade
      1/2/3, 3.8/2.8/1.9%), all patients recovered or improved. The median overall
      survival, the 1-year survival rate and median progression-free survival were 9.23
      months, 33.0% and 3.48 months, respectively. The overall response and disease
      control rates were 20.3% and 50.0%, respectively. In Japanese patients with
      unresectable pancreatic cancer, erlotinib plus gemcitabine had acceptable
      toxicity and efficacy that was not inferior to that seen in Western patients.

PMID- 21175993
TI  - Roles of intrinsic angiogenesis inhibitor, vasohibin, in cervical carcinomas.
AB  - The aim of the present study is to clarify the critical roles of vasohibin in
      cervical carcinomas. We investigated the expression ratios of vasohibin and
      vascular endothelial growth factor (VEGF) receptor-2 on endothelium and
      microvessel density, lymphatic vessel density (LVD) by immunohistochemistry.
      Sixty-one squamous cell carcinoma (SCC), 18 mucinous adenocarcinoma
      (Adenocarcinoma), 38 carcinoma in situ (CIS), and 35 normal cervical epithelium
      were collected. We investigated the expression of vasohibin and compared it with
      the expression of VEGF receptor-2 (VEGFR-2, KDR/flk-1), and CD34 in the stromal
      endothelium. Expression of VEGF was counted using the histological score (H
      score). D2-40 was used as a marker for lymphatic endothelial cells to investigate
      LVD. The microvessel density of the normal cervical epithelium was significantly
      lower than that of CIS, SCC, and Adenocarcinoma (P < 0.05). The expression ratio
      of vasohibin in the normal cervical epithelium was significantly lower than that
      of SCC and Adenocarcinoma (P < 0.05). The expression ratio of VEGFR-2 of the
      normal cervical epithelium was significantly lower than that of SCC and
      Adenocarcinoma (P < 0.05). The LVD of the normal cervical epithelium was
      significantly lower than that of CIS, SCC, and Adenocarcinoma (P < 0.05). For
      normal cervical epithelium, CIS, and SCC, there was a moderate correlation
      between the expression percentage of vasohibin and the expression percentage of
      VEGFR-2 (P < 0.05, r(2) = 0.3018). This is the first study to elucidate the
      correlation between the expression of vasohibin in the stromal endothelial cells
      and the expression of VEGFR-2 in human cervical carcinomas.

PMID- 21175994
TI  - Spontaneous immunogenicity of ribosomal P0 protein in patients with benign and
      malignant breast lesions and delay of mammary tumor growth in P0-vaccinated mice.
AB  - A common carboxyl-terminal epitope (C-22 P0) of the ribosomal P proteins (P0, P1
      and P2) was shown to elicit autoantibodies in systemic lupus erythematosus (SLE)
      and in head and neck cancer patients. In this report we provide evidence for the
      in vivo immunogenicity of the P0 protein in breast cancer patients. Using
      recombinant P proteins, we demonstrated that sera from breast carcinoma patients
      (8/75) displayed significant reactivity to P0 protein when compared with healthy
      donor sera (0/45). Four out of the eight sera showed simultaneous reactivity to
      all P proteins. Breast benign tumor (3/17) and mammary hyperplasia (3/17) patient
      sera also showed significant reactivity to P proteins, thus suggesting that the
      occurrence of P protein autoantibodies might reveal mammary cell cycle
      dysregulation. Patient sera reacting with all P proteins recognized C-22 P0. Anti
      P0 autoantibodies did not correlate with prognostic parameters of breast
      carcinomas. High level expression of C-22 P0 was found in mammary carcinomas
      compared with normal adjacent epithelium and benign lesions. To determine the
      antitumor activity of P0 as an immunogen, BALB-neuT transgenic mice displaying
      age-related breast cancer progression were vaccinated using xenogeneic P0 at the
      stage of mammary atypical hyperplasia. P0 vaccination significantly delayed the
      onset of mouse mammary tumors that overexpressed C-22 P0. Sera from P0 vaccinated
      mice recognized C-22 P0. Evidence for immunity to the P0 protein, its
      overexpression in carcinomas and its peculiar surface localization on cancer
      cells, along with its antitumor activity as an immunogen might be relevant for
      the use of P0 protein in monitoring cancer progression and in planning
      immunotherapeutic strategies.

PMID- 21175995
TI  - Effect of rikkunshito on gastric sensorimotor function under distention.
AB  - BACKGROUND: The herbal medicine rikkunshito is effective for the treatment of
      gastrointestinal symptoms in patients with functional dyspepsia. Although some
      basic studies on the effects of rikkunshito have been reported in rats, its
      effects on human gastric function have not yet been clarified. Psychosocial
      stress induces visceral hypersensitivity and elements of rikkunshito may
      reasonably affect or suppress this process. We conducted a study to verify the
      hypothesis that rikkunshito improves stress-induced gastric hypersensitivity
      and/or changes in gastric wall tone. METHODS: Nine healthy volunteers (five
      males, four females) participated in the study. The counterbalanced regimen
      consisted of a 2-week period of oral administration of 7.5 g day(-1) rikkunshito,
      then a 2-week period without treatment. Fundic sensorimotor function was examined
      using a gastric barostat twice on the day after each period. Virtual reality
      stress was imposed during the measurements of gastric tone and electrocardiogram.
      KEY RESULTS: Stress induced a significant increase in heart rate (P = 0.041),
      gastric volume (P = 0.008), and phasic volume events (P = 0.049) and a decrease
      in sensory (P = 0.038), discomfort (P = 0.011), and pain (P = 0.041) thresholds
      of the stomach. Rikkunshito significantly reduced epigastric fullness (P = 0.037)
      and perceived stress (P = 0.034) following stimulation of the pain threshold,
      regardless of stress without the drug. Stress reduced gastric volume at the
      sensory threshold and increased anxiety at the discomfort threshold, and these
      responses were significantly inhibited by rikkunshito (P = 0.026, P = 0.022,
      respectively). CONCLUSIONS & INFERENCES: These findings suggest that rikkunshito
      may improve symptoms and impaired gastric accommodation under distention stimuli
      of the proximal stomach superimposed by stress.

PMID- 21175996
TI  - The frequency of apneas in very preterm infants is increased after non-acid
      gastro-esophageal reflux.
AB  - BACKGROUND: To evaluate whether physical and/or chemical features of gastro
      esophageal reflux (GER) influence its relationship with apnea of prematurity
      (AOP). METHODS: Fifty-eight preterm newborns (GA <= 33 weeks) with recurrent
      apneas were studied by simultaneous polysomnography and combined impedance and pH
      monitoring, to analyze whether the correlation between GER and AOP varies
      according to the acidity, duration and height of GERs. KEY RESULTS: The frequency
      of apnea (number apnea/min) occurring after-GER [median (range) 0.07 (0-0.25)]
      was higher than the one detected in GER-free period [0.06 (0.04-0.13), P =
      0.015], and also than the one detected before-GER [0 (0-0.8), P = 0.000]. The
      frequency of apneas detected in the 30'' after pH-GER [median (range), 0 min(-1)
      (0-1.09)] was higher than the frequency detected in the 30'' before [0 (0-0.91),
      P = 0.04]; even more, the frequency of apneas detected after non-acid MII-GER
      episodes [0 (0-2)] was significantly higher than the one detected before [0 (0
      1), P = 0.000], whereas the frequency of apneas detected before acid MII-GER
      episodes [0 (0-0.67)] did not differ from the one detected after [0 (0-2), P =
      0.137]. The frequency of pathological apneas detected in the 30'' after-GER (0
      min(-1), range 0-0.55) was higher than the frequency detected before (0, range 0
      0.09; P = 0.001). No difference in mean height or in mean duration was found
      between GERs correlated and those non-correlated to apnea. CONCLUSIONS &
      INFERENCES: Non-acid GER is responsible for a variable amount of AOP detected
      after-GER: this novel finding must be taken into consideration when a therapeutic
      strategy for this common problem is planned.

PMID- 21175997
TI  - Quantitation of cellular components of the enteric nervous system in the normal
      human gastrointestinal tract--report on behalf of the Gastro 2009 International
      Working Group.
AB  - BACKGROUND: Patients with gastrointestinal neuromuscular diseases may undergo
      operative procedures that yield tissue appropriate to diagnosis of underlying
      neuromuscular pathology. Critical to accurate diagnosis is the determination of
      limits of normality based on the study of control human tissues. Although robust
      diagnostic criteria exist for many qualitative alterations in the neuromuscular
      apparatus, these do not include quantitative values due to lack of adequate
      control data. PURPOSE: The aim of this report was to summarize all relevant
      available published quantitative data for elements of the human enteric nervous
      system (neuronal cell bodies, glial cells, and nerve fibers) from the perspective
      of the practicing pathologist. Forty studies meeting inclusion criteria were
      systematically reviewed with data tabulated in detail and discussed in the
      context of methodological variations and limitations. The results reveal a lack
      of concordance between observations of different investigators resulting in data
      insufficient to produce robust normal ranges. This diversity highlights the need
      to standardize the way pathologists collect, process, and quantitate neuronal and
      glial elements in enteric neuropathologic samples, as suggested by recent
      international guidelines on gastrointestinal neuromuscular pathology.

PMID- 21175998
TI  - Nervous system tumors in adult immigrants to Sweden by subsite and histology.
AB  - BACKGROUND: The coding of histology of nervous system (NS) tumors with various
      degrees of malignancies differs between cancer registries, whereby the comparison
      of incidence rates from one registry to another seems difficult. No study has
      systematically defined whether the change in the risk of NS tumors upon
      immigration in adulthood varies by subsite or histology. Therefore, we aimed to
      address this issue amongst the first-generation immigrants to Sweden based on a
      large uniform cancer registry data (1958-2006). METHODS: The nationwide Swedish
      Family-Cancer Database (2008 version; >11.8 million individuals; 1.8 million
      immigrants; histology code in force since 1958) was used to calculate
      standardized incidence ratios (SIRs). We analyzed 28,981 adult cases of NS tumors
      amongst Swedes and 2519 amongst immigrants (age >= 30). RESULTS: Significantly
      decreased risks for brain glioma were amongst German (SIR = 0.64), Eastern
      European (0.62), some Asian (0.71), Chilean (0.34), and African immigrants
      (0.52). We found an increased risk for brain meningioma amongst Finns (1.15) and
      former Yugoslavians (1.33), whilst only Norwegians (0.71) and Latin Americans
      (0.21) had a decreased risk. The risk for spinal ependymoma and astrocytoma was
      increased in Germans (3.66) and former Yugoslavians (8.89). We found no
      significant difference for peripheral nerve tumors between immigrants and the
      native Swedes. CONCLUSION: Significant differences between risk of NS tumors
      amongst immigrants and the native Swedes may suggest different risk factor
      profiles for glioma compared to meningioma indicating a higher etiological role
      of genetic background or childhood environmental risk factors rather than
      exposures after immigration.

PMID- 21175999
TI  - Cost-effectiveness of decompressive craniectomy in traumatic brain injuries.
AB  - BACKGROUND AND PURPOSE: Decompressive craniectomy (DC) is used regularly in
      traumatic brain injury (TBI). There are, however, no cost-effectiveness studies
      of the procedure. METHODS: We evaluated the outcomes and treatment costs of all
      decompressive craniectomies performed between the 2000 and 2006 in a single
      institution to lower intractable intracranial pressure after TBI. The health
      related quality of life was evaluated on the Euroqol (EQ-5D) questionnaire and on
      the visual-analogue scale (VAS), and cost of a quality-adjusted life year (QALY)
      was calculated. RESULTS: In this study of 54 patients, the median follow-up time
      was 5.6 years. Overall mortality rate was 41%. Of the 22 non-survivors, 73% died
      within 30 days. For 32 survivors, the median EQ-5D index value was 0.85, which is
      equal to the normal population. The median VAS value was 73, whilst normal
      population's value is 80. Of the survivors, 81% (26/32) were able to live at home
      and 31% (10/32) returned to work. The cost of neurosurgical treatment for one
      QALY was 2400 ?. Estimation for all medical costs, including rehabilitation and
      anticipated future costs, resulted cost of a QALY 17,900 ?. CONCLUSION: Mortality
      after severe TBI leading to DC was high, but amongst the survivors, the health
      related quality of life was equal to normal population. Most survivors were able
      to live at home and were almost as satisfied with their health as in general
      people are. Cost of neurosurgical treatment was low, and also including all
      evaluated costs, cost of a QALY gained was acceptable.

PMID- 21176000
TI  - EHR adoption among doctors who treat the elderly.
AB  - OBJECTIVES: The purpose of this study is to examine Electronic Health Record
      (EHR) adoption among Florida doctors who treat the elderly. This analysis
      contributes to the EHR adoption literature by determining if doctors who
      disproportionately treat the elderly differ from their counterparts with respect
      to the utilization of an important quality-enhancing health information
      technology application. METHODS: This study is based on a primary survey of a
      large, statewide sample of doctors practising in outpatient settings in Florida.
      Logistic regression analysis was used to determine whether doctors who treat a
      high volume of elderly (HVE) patients were different with respect to EHR
      adoption. RESULTS: Our analyses included responses from 1724 doctors. In
      multivariate analyses controlling for doctor age, training, computer
      sophistication, practice size and practice setting, HVE doctors were
      significantly less likely to adopt EHR. Specifically, compared with their
      counterparts, HVE doctors were observed to be 26.7% less likely to be utilizing
      an EHR system (OR=0.733, 95% CI 0.547-0.982). We also found that doctor age is
      negatively related to EHR adoption, and practice size and doctor computer savvy
      ness is positively associated. CONCLUSIONS: Despite the fact that EHR adoption
      has improved in recent years, doctors in Florida who serve the elderly are less
      likely to adopt EHRs. As long as HVE doctors are adopting EHR systems at slower
      rates, the elderly patients treated by these doctors will be at a disadvantage
      with respect to potential benefits offered by this technology.

PMID- 21176001
TI  - Discharge management for patients in Flemish psychiatric hospitals.
AB  - RATIONALE AND AIMS: At the end of the 1990 s, a case management service called
      'discharge management' was implemented in Belgian psychiatric hospitals. This
      study aimed to describe the profile of patients receiving discharge management in
      Flemish psychiatric hospitals as well as to analyse the discharge management
      indicators of these hospitals on micro and meso level. METHODS: Ten Flemish
      psychiatric hospitals participated. A descriptive analysis of the profile of
      patients receiving discharge management (gender, age, length of stay, family
      situation, assistance at home, living environment and Global Assessment of
      Functioning) and of the indicators of discharge management (screening,
      interdisciplinary patient file, interdisciplinary meeting, timely announcement of
      discharge date, transfer of discharge documents, readmission and
      institutionalization) were carried out. RESULTS: Of the 1306 patients included in
      the database, one-fourth received discharge management. In general, patients (54%
      were male) were about 45 years old, stayed for 55 days in hospital, were single
      and had no aid at home. Most of them came from and returned to their own home. On
      the micro level of discharge management, nearly all patients were screened and
      half of them were positively screened. Half of these patients received discharge
      management. Of the discharged patients who received discharge management (meso
      level), 13.5% were institutionalized after discharge, 37.6% had been previously
      admitted and 27.2% received discharge management during that previous admission.
      Differences between diagnostic groups occurred. CONCLUSION: Hospitals have made
      efforts to support and prepare patients for discharge, although a number of
      improvements are suggested for different indicators.

PMID- 21176002
TI  - Hypoglycaemia with pioglitazone: analysis of data from the Prescription-Event
      Monitoring study.
AB  - AIMS AND OBJECTIVES: To investigate the relationship between patients'
      characteristics, use of concomitant anti-diabetic therapies and the incidence of
      hypoglycaemia, an acute complication of the treatment of diabetes mellitus
      reported by general practitioners (GPs) during the first 9 months of the
      treatment with pioglitazone. METHODS: We used data collected for the Prescription
      Event Monitoring (PEM) study conducted by the Drug Safety Research Unit for
      patients prescribed pioglitazone between November 2000 and June 2001 by their GP
      in England. A Cox proportional-hazards regression model was used to assess this
      relationship. RESULTS: The original pioglitazone PEM cohort included 12,772
      patients (mean age 60.9 years); 53% (6777) were male. A total of 77 patients
      experienced at least one hypoglycaemic episode (9.64 per 1000 patient-years).
      Women were estimated to have twice the hazard of having a hypoglycaemic event
      compared with men [hazard ratio (HR) 2.05; confidence interval (CI) 1.24, 3.41].
      Patients taking combination therapy with sulfonylurea or insulin were estimated
      to have approximately three and four times the hazard of having an event compared
      with those who were not taking these adjunctive therapies [HR=3.11 (CI 1.64,
      5.88); HR=4.15 (CI 1.74, 9.91), respectively]. Patients treated with adjunctive
      metformin were 25% less likely to experience hypoglycaemia than those who did not
      take concomitant metformin (HR=0.75; CI 0.44, 1.27). CONCLUSIONS: This study has
      shown that the treatment with pioglitazone was associated with a low incidence of
      hypoglycaemia. The factors possibly increasing the risk of hypoglycaemia were
      concomitant therapy with sulfonylurea or insulin and female gender.

PMID- 21176003
TI  - FabAct(r): a decision-making tool for the anticipation of the preparation of
      anticancer drugs.
AB  - RATIONALE: Due to the increase of new cancer cases, our chemotherapy compounding
      unit must face with ever-growing production needs. To support this increasing
      workload, we decided to anticipate the preparation of several anti-cancer drugs.
      AIMS AND OBJECTIVES: To help us in the decision making, we needed a modern tool
      able to combine several criteria for selecting appropriate medications for an
      anticipated preparation. The aim of this study was to assess the decision-making
      software, FabAct((r)) (Version 1.0). METHODS: FabAct((r)) ranked all of the anti
      cancer drugs used in our chemotherapy compounding unit according to price,
      chemical stability, compounding difficulties, dosage and production per year.
      Then, we started to anticipate currently the preparation of four medications and
      conducted a follow-up of destroyed preparations between January and May 2007. We
      tried to identify the destruction causes and calculated the time saved for the
      patients and for the pharmacy technicians. RESULTS: According to the decision
      making software, the first four drugs for an anticipated preparation were:
      fluorouracil, cisplatin, carboplatin and paclitaxel. A total of 3913 (50.2%)
      anticipated preparations were performed and among those, 470 (12%) were
      destroyed. The main cause of destruction was due to the preparation expiration.
      Finally, the mean waiting time per patient was reduced from 118 minutes to 68
      minutes after the application of the anticipated model. CONCLUSION: According to
      this 5-month follow-up, FabAct((r)) helped us to select appropriate anti-cancer
      drugs to anticipate the compounding. Most of the anticipated preparations were
      administrated to patients and the patient waiting time was significantly reduced.

PMID- 21176004
TI  - Doctors' perceptions of laboratory monitoring in office practice.
AB  - BACKGROUND: Laboratory monitoring has been increasingly recognized as an
      important area for improving patient safety in ambulatory care. Little is known
      about doctors' attitudes towards laboratory monitoring and potential ways to
      improve it. METHODS: Six focus groups and one individual interview with 20
      primary care doctors and nine specialists from three Massachusetts communities.
      RESULTS: Participants viewed laboratory monitoring as a critical, time-consuming
      task integral to their practice of medicine. Most believed they commit few
      laboratory monitoring errors and were surprised at the error rates reported in
      the literature. They listed various barriers to monitoring, including not knowing
      which doctor was responsible for ensuring the completion of laboratory
      monitoring, uncertainty regarding the necessity of monitoring, lack of
      alerts/reminders and patient non-adherence with recommended monitoring. The
      primary facilitator of monitoring was ordering laboratory tests while the patient
      is in the office. Primary care doctors felt more strongly than specialists that
      computerized alerts could improve laboratory monitoring. Participants wanted to
      individualize alerts for their practices and warned that alerts must not
      interrupt work flow or require too many clicks. CONCLUSIONS: Doctors in community
      practice recognized the potential of computerized alerts to enhance their
      monitoring protocols for some medications. They viewed patient non-adherence as a
      barrier to optimal monitoring. Interventions to improve laboratory monitoring
      should address doctor workflow issues, in addition to patients' awareness of the
      importance of fulfilling recommended therapeutic monitoring to prevent adverse
      drug events.

PMID- 21176006
TI  - A primary care level algorithm for identifying HIV-infected adolescents in
      populations at high risk through mother-to-child transmission.
AB  - OBJECTIVE: To present an algorithm for primary-care health workers for
      identifying HIV-infected adolescents in populations at high risk through mother
      to-child transmission. METHODS: Five hundred and six adolescent (10-18 years)
      attendees to two primary care clinics in Harare, Zimbabwe, were recruited. A
      randomly extracted 'training' data set (n = 251) was used to generate an
      algorithm using variables identified as associated with HIV through multivariable
      logistic regression. Performance characteristics of the algorithm were evaluated
      in the remaining ('test') records (n = 255) at different HIV prevalence rates.
      RESULTS: HIV prevalence was 17%, and infection was independently associated with
      client-reported orphanhood, past hospitalization, skin problems, presenting with
      sexually transmitted infection and poor functional ability. Classifying
      adolescents as requiring HIV testing if they reported >1 of these five criteria
      had 74% sensitivity and 80% specificity for HIV, with the algorithm correctly
      predicting the HIV status of 79% of participants. In low-HIV-prevalence settings
      (<2%), the algorithm would have a high negative predictive value (>= 99.5%) and
      result in an estimated 60% decrease in the number of people needing to test to
      identify one HIV-infected individual, compared with universal testing.
      CONCLUSIONS: Our simple algorithm can identify which individuals are likely to be
      HIV infected with sufficient accuracy to provide a screening tool for use in
      settings not already implementing universal testing policies among this age
      group, for example immigrants to low-HIV-prevalence countries.

PMID- 21176007
TI  - Antimicrobial cationic surfactant, cetyltrimethylammonium bromide, induces
      superoxide stress in Escherichia coli cells.
AB  - AIMS: To clarify whether an antibacterial surfactant, cetyltrimethylammonium
      bromide (CTAB), induces superoxide stress in bacteria, we investigated the
      generation of superoxide and hydrogen peroxide and expression of soxR, soxS and
      soxRS regulon genes in Escherichia coli cells with the treatment of CTAB. METHODS
      AND RESULTS: In situ oxidative stress analyses with BES fluorescent probes
      revealed that generation of both superoxide and hydrogen peroxide were
      significantly increased with the CTAB treatment at a sublethal concentration in
      wild-type strain OW6, compared with the CTAB-resistant strain OW66. The activity
      of manganese-superoxide dismutase (Mn-SOD), a member of the soxRS regulon
      proteins, was decreased by the CTAB treatment only in strain OW6. Furthermore,
      quantitative real-time PCR analyses revealed that expression of the soxRS regulon
      genes was not upregulated, although soxS was upregulated by the CTAB treatment in
      strain OW6. CONCLUSIONS: Cetyltrimethylammonium bromide treatment led E. coli
      cells to a generation state of superoxide and hydrogen peroxide. It was also
      suggested that superoxide generation was caused by inhibiting SoxS function and
      decreasing Mn-SOD activity. SIGNIFICANCE AND IMPACT OF THE STUDY:   It was
      revealed that excess superoxide generation in bacterial cells play a key action
      of antibacterial surfactants.

PMID- 21176008
TI  - Is exercise-induced pulmonary hypertension ready for prime time in systemic
      sclerosis?

PMID- 21176009
TI  - Clinical perspective: biomarkers in pulmonary arterial hypertension.
AB  - Biomarkers are objectively measured characteristics used as indicators of disease
      in clinical practice and as surrogate endpoints in clinical trials. The six
      minute walk test has been widely used as a trial endpoint in pulmonary arterial
      hypertension (PAH) to gain approval for targeted therapies. Other biomarkers have
      been studied to overcome certain limitations of the walk test. Potential clinical
      applications for biomarkers in PAH include screening, determination of prognosis,
      and monitoring response to therapy. Measurement of the B-type natriuretic
      peptides is currently recommended by guidelines, despite a lack of appropriate
      validation in the PAH population. Novel biomarkers based on recently discovered
      pathobiologic pathways have been identified, like CXC chemokine ligand 10, C
      reactive protein, high-density lipoprotein cholesterol and growth-differentiation
      factor-15. Rigorous statistical, biologic and clinical validation should be
      necessary before any biomarker can be endorsed for widespread clinical use.

PMID- 21176010
TI  - Drugs and toxins-associated pulmonary arterial hypertension: lessons learned and
      challenges ahead.
AB  - Since the identification of the link between pulmonary arterial hypertension
      (PAH) and exposure to certain drugs and toxins nearly fifty years ago, the
      expanding landscape of available pharmaceuticals and illicit drugs is further
      fueling this association. While some causative agents in drugs and toxins
      associated PAH (D&T-APAH) have been identified, little is known about the exact
      biology and clinical implications of the disease. In this review, we discuss the
      historical evidence that links PAH with exposure to anorexinogens, cocaine, and
      methamphetamines and concentrate on what is known about potential pathogenesis,
      clinical manifestations, and current management. We conclude that future research
      should focus on studies looking at clinical outcome and susceptibility factors.

PMID- 21176011
TI  - Current management approaches to portopulmonary hypertension.
AB  - Portopulmonary hypertension (PoPH) is a rare but life-threatening complication of
      portal hypertension that is characterised by proliferative changes in the
      pulmonary microvasculature indistinguishable from other forms of pulmonary
      arterial hypertension (PAH). Although PoPH is most commonly observed in the
      setting of cirrhosis, patients with non-cirrhotic portal hypertension are also at
      risk of developing the disorder. A definitive diagnosis requires invasive
      haemodynamic confirmation by right heart catheterisation and screening for PoPH
      should be routinely performed in all patients being considered for liver
      transplantation. Although severe PoPH is considered a contraindication to liver
      transplantation, there is now compelling data supporting the use of PAH-specific
      therapies with the aim of improving pulmonary haemodynamics to allow
      transplantation to be successfully performed. This review explores possible
      relevant aetiological factors and summarises current diagnostic and therapeutic
      approaches for PoPH patients.

PMID- 21176012
TI  - Microarray studies in pulmonary arterial hypertension.
AB  - Microarray studies have been performed on lung tissue, freshly isolated
      circulating cells and cells cultured from patients with idiopathic, hereditary
      and secondary forms of pulmonary arterial hypertension (PAH). These studies have
      provided a wealth of information on the characteristics of end-stage disease, but
      information about the origin of disease is only clear in hindsight. The central
      conclusions that can be drawn from these studies are that end-stage disease
      includes a massive but currently poorly defined inflammatory response, induction
      of angiogenesis genes for an as yet remaining unknown purpose, suppression of the
      BMP pathway even in idiopathic and secondary cases, and a host of more subtle
      changes, including mitochondrial and actin organisation changes. Moreover, the
      same physiologic endpoints can be achieved through use of any of multiple genes,
      and so specific genes are usually less important than the pathways they lie in;
      the exception to this rule must lie in as yet undefined critical nodes. Finally,
      the lack of consistency in methodologies of analysis makes cross-experiment
      comparisons difficult, and likely means that there is data collected in these
      studies that await interpretation.

PMID- 21176013
TI  - Patient-expert partnerships in research: how to stimulate inclusion of patient
      perspectives.
AB  - OBJECTIVE To gain more insight into exclusion mechanisms and inclusion strategies
      in patient-expert partnerships. BACKGROUND Patient participation in health
      research, on the level of 'partnerships with experts' is a growing phenomenon.
      However, little research is conducted whether exclusion mechanisms take place and
      to what extent patients' perspectives are included in the final outcomes of these
      partnerships. Case study  A dialogue meeting attended by experts, patients and
      patient representatives to develop a joint research agenda. Different inclusion
      strategies were applied during the dialogue meeting to avoid possible exclusion.
      METHOD Data were collected by the means of audio and video recordings,
      observations, document analysis and evaluative interviews. The data are clustered
      using a framework that divides exclusion mechanisms in three categories:
      circumstances, behaviour and verbal communication. The data are analysed focusing
      on the experiences of participants, observation of occurrence of exclusion and
      difference between input and outcome of the dialogue meeting. RESULTS The
      circumstances of the dialogue and the behaviour of the participants were
      experienced as mainly inclusive. Some exclusion was observed particularly with
      respect to verbal communication. The input of the patients was less visible in
      the outcome of the dialogue meeting compared to the input of the experts.
      CONCLUSION This case study reveals that exclusion of patients' perspective
      occurred during a dialogue meeting with experts, despite the fact that inclusion
      strategies were used and patients experienced the dialogue meeting as inclusive.
      To realize a more effective patient-expert partnership, more attention should be
      paid to the application of some additional inclusion strategies.

PMID- 21176014
TI  - Patients' and clinicians' research priorities.
AB  - BACKGROUND: If research addresses the questions of relevance to patients and
      clinicians, decision-makers will be better equipped to design and deliver health
      services which meet their needs. To this end, a number of initiatives have
      engaged patients and clinicians in setting research agendas. This paper aimed to
      scope the research literature addressing such efforts. METHODS: A systematic
      search strategy combined electronic searches of bibliographic databases with
      handsearching and contacting key authors. Two researchers, initially working
      independently, described the relevant reports. FINDINGS: Over 250 studies
      addressed patients' or clinicians' priorities for research and outcomes for
      assessment. This literature described different routes for patients and
      clinicians to contribute to research agendas. Two-thirds of the studies
      addressing patients' or clinicians' research questions were applicable across
      health care, with the remainder focussed on specific health conditions. The 27
      formal studies of patient involvement revealed a literature that has grown in the
      last decade. Although only nine studies engaged patients and clinicians in
      identifying research questions together, they show that methods have advanced
      over time, with all of them engaging participants directly and repeatedly in
      facilitated debate and most employing formal decision-making procedures.
      CONCLUSION: A sizeable literature is available to inform priorities for research
      and the methods for setting research agendas with patients and clinicians. We
      recommend that research funders and researchers draw on this literature to
      provide relevant research for health service decision-makers.

PMID- 21176015
TI  - Stevens-Johnson syndrome after Mycoplasma pneumonia infection in pediatric post
      liver transplant recipient: case report and review of the literature.
AB  - Although Mycoplasma pneumonia infection is relatively common among school-aged
      children, it rarely leads to SJS. Herein, we report a seven-yr-old girl who
      presented with a Mycoplasma pneumonia infection that progressed to SJS five
      months after liver transplant. We suggest that children presenting with symptoms
      of Mycoplasma pneumonia infection in the immunosuppressed post-liver transplant
      setting be properly diagnosed and treated rapidly, as well as observed for
      symptoms of SJS and potentially serious extrapulmonary complications.

PMID- 21176016
TI  - Reduced-intensity conditioning for alternative donor hematopoietic stem cell
      transplantation in patients with dyskeratosis congenita.
AB  - DC is an inherited bone marrow failure syndrome mainly characterized by nail
      dystrophy, abnormal skin pigmentation, and oral leukoplakia. Bone marrow failure
      is the most common cause of death in patients with DC. Because previous results
      of HSCT with a myeloablative regimen were disappointing, we used a reduced
      intensity conditioning regimen for two patients with classic DC, and one patient
      with cryptic DC who harbored the TERT mutation. Graft sources included two
      mismatched-related bone marrow (BM) donors and one unrelated BM donor. Successful
      engraftment was achieved with few regimen-related toxicities in all patients.
      They were alive 10, 66, and 72 months after transplantation, respectively. Long
      term follow-up is crucial to determine the late effects of our conditioning
      regimen.

PMID- 21176017
TI  - Early post-transplant vaccination with pandemic influenza A/H1N1 vaccine in
      pediatric heart transplant recipients.
AB  - Pandemic influenza A/H1N1 virus has the potential to cause severe disease in
      pediatric transplant patients. A pandemic vaccine against H1N1 is effective in
      immunocompetent children. We investigated the immunogenicity of this vaccine when
      given in the first six months after heart transplantation. Four patients younger
      than two yr received two doses of vaccine and one patient older than seven yr
      received one dose. Titers were obtained using the HAI at baseline and after final
      immunization. Five patients were enrolled, ages 0.5-7 yr. Median age at the time
      of transplant was five months (range 3 wk-7 yr). All patients received induction
      with anti-thymoglobulin and maintenance immunosuppression with tacrolimus, MMF,
      and prednisone. Patients were immunized with the adjuvanted H1N1 vaccine after
      heart transplant at median time of nine wk (range 5-23 wk) post-transplant. Three
      of five developed protective titers against H1N1. A proportion of pediatric
      patients may respond to influenza vaccine even when immunized in the early post
      transplant period.

PMID- 21176018
TI  - Safety and efficacy of tacrolimus in pediatric liver recipients.
AB  - Pediatric liver transplantation is now so successful that we expect more than 80%
      of children to survive into adolescence and adulthood. As the focus of care
      shifts toward long-term patient management, immunosuppressive regimens should, in
      addition to preventing acute and chronic rejection, promote good quality of life
      and be free of significant long-term side effects. Historically, the most
      effective immunosuppressive regimens have been based on induction with a
      combination of calcineurin inhibitors (cyclosporin or tacrolimus) and steroids.
      Usually, maintenance is monotherapy with cyclosporin or tacrolimus or dual
      therapy with low-dose alternate-day steroids to encourage growth. A number of
      studies, including long-term follow-up, have shown significantly lower incidences
      of rejection, hypertension, hyperlipidemia and cosmetic side effects in patients
      treated initially with tacrolimus compared with cyclosporin. The use of anti
      interleukin-2 inhibitors as induction therapy, with low-dose tacrolimus or in
      combination with mycophenolate mofetil, has a key role in preventing significant
      renal dysfunction and reducing infection and rejection. Steroid-free
      immunosuppression is also proving to be an effective option for the management of
      pediatric liver recipients. The main challenges now facing pediatricians include
      ensuring long-term quality of life, optimizing immunosuppression while preventing
      associated adverse events, and managing a smooth transition from childhood to
      adolescence and adulthood.

PMID- 21176019
TI  - Proceedings from a satellite symposium at the International Pediatric Transplant
      Association (IPTA): Fifth Congress on Pediatric Transplantation.

PMID- 21176020
TI  - Management of voriconazole hepatotoxicity in a lung transplant patient.
AB  - Lung allograft airway colonization by Aspergillus species is common among lung
      transplant recipients. We report the case of a 46-year-old female lung transplant
      outpatient diagnosed with persistent pulmonary Aspergillus colonization (>50
      colonies of Aspergillus terreus) 3 months after lung transplantation. Oral
      voriconazole 200 mg twice a day (b.i.d) was initiated shortly after diagnosis.
      Two days after voriconazole initiation, alkaline phosphatase (ALP), alanine
      transaminase (ALT), and aspartate transaminase (AST) were normal or slightly
      elevated (79, 37, and 21 UI/L, respectively). Ten days after the first
      voriconazole administration, these values started to increase. Maximum levels
      were reached after 20 days for ALP (369 UI/L) and at around 30 days for ALT and
      AST (223 and 188 UI/L, respectively). Instead of discontinuing antifungal
      therapy, it was decided to reduce the voriconazole dose to 100 mg b.i.d. This
      asymptomatic progressive cholestatic hepatitis resolved, and 10 days after dose
      reduction ALP, ALT, AST were at 136, 53, and 28 UI/L, respectively. Finally,
      therapeutic drug monitoring revealed adequate voriconazole plasma trough
      concentrations (0.98 mg/L) 30 days after dose reduction and no more colonies of
      Aspergillus were observed. Voriconazole-induced hepatotoxicity is a well known
      dose-dependent adverse drug reaction. This experience confirms the
      appropriateness of voriconazole dose reduction instead of therapy interruption in
      dose-dependent moderate liver toxicity. Voriconazole therapeutic drug monitoring
      before and after dose reduction may help to avoid drug accumulation and
      inappropriately low drug exposure, respectively.

PMID- 21176021
TI  - Factors influencing the performance level of Candida mannan antigen testing in
      allogeneic stem cell transplant recipients not receiving fluconazole prophylaxis.
AB  - In this study, we evaluated the value of the Platelia((r)) Candida mannan antigen
      (Ag) sandwich enzyme-linked immunosorbent assay test in the diagnosis of invasive
      candidiasis (IC) and the degree of oral colonization by Candida species in 102
      allogeneic stem cell transplantation recipients who were not receiving
      fluconazole prophylaxis. Of the 2071 serum samples, 98 (4.7%) yielded positive
      and 78 (3.8%) borderline results with a cut-off value of 0.5 ng/mL. One patient
      had IC. In this patient, 6 out of 9 serum samples were positive, the first one 49
      days before Candida albicans candidemia. False-positive results occurred in 92
      (4.4%) samples and in 54 (52.9%) patients. Use of valacyclovir and acyclovir was
      associated with false-positive or borderline results. The median Ag concentration
      of the true-positive results was significantly higher than the concentration of
      the false-positive results (1.60 versus 0.62 ng/mL, P<0.001). With higher cut-off
      values of 0.75 and 1.0 ng/mL, false-positive Ag test results were seen in 17 and
      7 patients, respectively. Of the 657 oral samples, a total of 92 (14%) samples in
      39 (38.2%) patients turned out to be positive. C. albicans grew in 82 samples
      (89.1%), other Candida species in 9 (9.8%), and Aspergillus fumigatus in 1 sample
      (1.1%). In conclusion, despite the lack of fluconazole prophylaxis, the incidence
      of IC was low (1%). False-positive Ag test results were common with a test cut
      off value of 0.5 ng/mL, and a single positive result does not seem to predict IC.
      Multiple positive results might predict IC, as 6 out of 9 samples were positive
      in the only patient with IC, the first one 7 weeks before positive blood
      cultures.

PMID- 21176022
TI  - Editorial. A new initiative, the Bipolar Bulletin.

PMID- 21176023
TI  - Hypomania: hype or mania?

PMID- 21176024
TI  - Striatal structure and function in mood disorders: a comprehensive review.
AB  - OBJECTIVES:   A large and diverse literature has implicated abnormalities of
      striatal structure and function in both unipolar and bipolar disorder. Recent
      functional imaging studies have greatly expanded this body of research. The aim
      of this review is to provide a comprehensive and critical appraisal of the
      relevant literature. METHODS:   A total of 331 relevant articles were reviewed to
      develop an integrated overview of striatal function in mood disorders. RESULTS:  
      There is compelling evidence from multiple studies that functional abnormalities
      of the striatum and greater corticostriatal circuitry exist in at least some
      forms of affective illness. The literature does not yet provide data to determine
      whether these aberrations represent primary pathology or they contribute directly
      to symptom expression. Finally, there is considerable evidence that bipolar
      disorder may be associated with striatal hyperactivity and some suggestion that
      unipolar illness may be associated with hypoactivation. CONCLUSIONS:   Additional
      research investigating striatal function in affective disorders will be critical
      to the development of comprehensive models of the neurobiology of these
      conditions.

PMID- 21176025
TI  - Family-based association analysis to finemap bipolar linkage peak on chromosome
      8q24 using 2,500 genotyped SNPs and 15,000 imputed SNPs.
AB  - OBJECTIVE:   Multiple linkage and association studies have suggested chromosome
      8q24 as a promising candidate region for bipolar disorder (BP). We performed a
      detailed association analysis assessing the contribution of common genetic
      variation in this region to the risk of BP. METHODS:   We analyzed 2,756 single
      nucleotide polymorphism (SNP) markers in the chromosome 8q24 region of 3,512
      individuals from 737 families. In addition, we extended genotype imputation
      methods to family-based data and imputed 22,725 HapMap SNPs in the same region on
      8q24. We applied a family-based method to test 15,552 high-quality genotyped or
      imputed SNPs for association with BP. RESULTS:   Our association analysis
      identified the most significant marker (p=4.80 * 10(-5) ), near the gene encoding
      potassium voltage-gated channel KQT-like protein (KCNQ3). Other marginally
      significant markers were located near adenylate cyclase 8 (ADCY8) and ST3 beta
      galactoside alpha-2,3-sialyltransferase 1 (ST3GAL1). CONCLUSIONS:   We developed
      an approach to apply MACH imputation to family-based data, which can increase the
      power to detect association signals. Our association results showed suggestive
      evidence of association of BP with loci near KCNQ3, ADCY8, and ST3GAL1.
      Consistent with genes identified by genome-wide association studies for BP, our
      results suggest the involvement of ion channelopathy in BP pathogenesis. However,
      common variants are insufficient to explain linkage findings in 8q24; other
      genetic variation should be explored.

PMID- 21176026
TI  - Auditory steady state response in bipolar disorder: relation to clinical state,
      cognitive performance, medication status, and substance disorders.
AB  - OBJECTIVES:   Abnormalities in auditory steady state response (ASSR) at gamma
      range frequencies have been found in bipolar disorder, but the relationship of
      these neurophysiological disturbances to clinical factors has not been well
      characterized. We therefore evaluated the ASSR in bipolar disorder and examined
      its sensitivity to clinical symptoms, cognitive function, and pharmacological
      treatment. METHODS:   A total of 68 patients with bipolar disorder and 77 control
      participants were evaluated. Click trains presented at 20, 30, 40, and 50 Hz
      evoked ASSRs. Mean trial power (MTP) and phase locking factor (PLF) measured
      response magnitude and phase synchronization of the ASSR at each stimulation
      frequency. Clinical state, pharmacological treatment, and neuropsychological
      performance were assessed, and their respective relationships with ASSR measures
      were evaluated. RESULTS:   Patients with bipolar disorder showed reduced MTP and
      PLF compared to control participants. Bipolar disorder patients taking
      psychotropic medications had decreased PLF relative to patients withdrawn from
      medications. Control participants performed better on neuropsychological tests
      than bipolar disorder patients; however, test scores did not correlate with ASSR
      measures. CONCLUSIONS:   Deficits in the generation and maintenance of ASSR are
      present in bipolar disorder, implicating disturbances in auditory pathways. ASSR
      may be sensitive to medication status. Other clinical features, including mood
      state, psychotic features, cognitive performance, smoking, or history of
      substance use disorder, were unrelated to MTP or PLF.

PMID- 21176027
TI  - Differentiation between bipolar disorder and schizophrenia revealed by neural
      oscillation to speech sounds: an MEG study.
AB  - OBJECTIVES:   Psychiatrists have long debated whether bipolar disorder (BP) and
      schizophrenia (SZ) are the clinical outcomes of discrete or shared causative
      processes. SZ shows significantly delayed peak latencies of the evoked neural
      oscillation (eNO) power and reduced eNO power to speech sounds in the left
      hemisphere in comparison to normal controls (NC), suggesting deficits in the fast
      mechanism for identifying speech sounds for SZ. The current study tested the
      hypothesis that the eNO to speech sounds could be differentiated between BP and
      SZ patients. METHODS:   The magnetoencephalographic data of 11 BP, 12 SZ, and 15
      NC subjects were evaluated, and we analyzed the eNO power and phase-locking in 20
      45 Hz to speech sounds and pure tones in the left hemisphere. RESULTS:   The
      major findings were that: (i) BP subjects exhibited larger eNO power to speech
      sounds compared to NC and SZ; (ii) SZ subjects showed delayed eNO and phase
      locking to speech sounds specifically in the left hemisphere; and (iii) no
      significant differences were observed in the response to pure tones among the
      three groups. CONCLUSIONS:   The present study showed that different patterns in
      eNO to speech sounds are present in BP, SZ, and NC subjects. The eNO to speech
      sounds in the left hemisphere is a potential index to distinguish BP and SZ.

PMID- 21176028
TI  - Increased peripheral blood expression of electron transport chain genes in
      bipolar depression.
AB  - OBJECTIVE:   To identify specific genetic pathways showing altered expression in
      peripheral blood of depressed subjects with bipolar disorder (BPD). METHODS:  
      Illumina Sentrix BeadChip (Human-6v2) microarrays containing >48,000 transcript
      probes were used to measure levels of gene expression in peripheral blood from 20
      depressed subjects with BPD and in 15 healthy control subjects. Quantitative real
      time reverse transcription polymerase chain reaction (qRT-PCR) was used to
      confirm a subset of these differences. RESULTS:   A total of 1,180 genes were
      differentially expressed between subjects with BPD and healthy controls (fold
      change >1.3, false discovery rate-corrected p < 0.05, covaried for age and sex).
      Of these, 559 genes were up-regulated in BPD subjects and 621 were down
      regulated. Surprisingly, there was no difference between medicated (n = 11) and
      unmedicated (n = 9) subjects with BPD for any of these genes. Pathway analysis
      using GeneGo MetaCore software showed that the most significantly affected
      pathway was the mitochondrial electron transport chain (ETC). Of the 85 objects
      (genes or proteins) in this pathway, 22 were up-regulated and 2 down-regulated in
      subjects with BPD. qRT-PCR confirmed up-regulation of nuclear encoded ETC genes
      in complexes I, III, IV, and V and, in addition, demonstrated up-regulation of
      mitochondrially encoded genes in each of these complexes. CONCLUSION:   These
      results suggest that increased expression of multiple components of the
      mitochondrial ETC may be a primary deficit in bipolar depression, rather than an
      effect of medication.

PMID- 21176030
TI  - Immune activation by casein dietary antigens in bipolar disorder.
AB  - OBJECTIVES:   Inflammation and other immune processes are increasingly linked to
      psychiatric diseases. Antigenic triggers specific to bipolar disorder are not yet
      defined. We tested whether antibodies to bovine milk caseins were associated with
      bipolar disorder, and whether patients recognized different epitopes of the
      casein protein than control individuals. METHODS:   Anti-bovine casein
      immunoglobulin G (IgG) levels were measured with solid-phase immunoassays in 75
      individuals with bipolar disorder and 65 controls. Epitope recognition was
      evaluated in immunoassays by cross neutralization with anti-bovine casein
      polyclonal antibodies of defined reactivity. Group-specific reactivity and
      associations with symptom severity scores were detected with age-, gender-, and
      race-controlled regression models. RESULTS:   Individuals with bipolar disorder
      had significantly elevated anti-casein IgG (t-test, p <=0.001) compared to
      controls. Casein IgG seropositivity conferred odds ratios of 3.97 for bipolar
      disorder [n=75, 95% confidence interval (CI): 1.31-12.08, p <=0.015], 5.26 for
      the bipolar I subtype (n=56, 95% CI: 1.66-16.64, p <=0.005), and 3.98 for bipolar
      disorder with psychosis (n=54, 95% CI: 1.32-12.00, p <=0.014). Lithium and/or
      antipsychotic medication did not significantly affect anti-casein IgG levels.
      Casein IgG measures correlated with severity of manic (R(2) =0.15, 95% CI: 0.05
      0.24, p <=0.02) but not depressive symptoms. Unlike controls, sera from
      individuals with bipolar disorder did not inhibit binding of casein-reactive
      animal sera (t-test/chi(2) , p <=0.0001). CONCLUSIONS:   Anti-casein IgG
      associations with bipolar I diagnoses, psychotic symptom history, and mania
      severity scores suggest that casein-related immune activation may relate to the
      psychosis and mania components of this mood disorder. Case-control differences in
      epitope recognition implicate disease-related alterations in how the casein
      molecule is digested and/or how resulting casein-derived structures are rendered
      immunogenic.

PMID- 21176029
TI  - Short-term administration of uridine increases brain membrane phospholipid
      precursors in healthy adults: a 31-phosphorus magnetic resonance spectroscopy
      study at 4T.
AB  - OBJECTIVES:   Altered metabolism of membrane phospholipids has been implicated in
      bipolar disorder. In humans, uridine is an important precursor of cytidine
      diphosphate (CDP)-choline, which plays a critical role in phospholipid synthesis
      and is currently being evaluated as a potential treatment for bipolar depression.
      METHODS:   A total of 17 healthy males (mean age +/- SD: 32.73 +/- 7.2 years;
      range: 21.8-46.4 years) were enrolled in this study. Subjects underwent a 31
      phosphorus magnetic resonance spectroscopy ((31) P-MRS) acquisition at baseline
      and then again after seven days of either 2 g of uridine or placebo
      administration. A two-dimensional chemical shift imaging (31) P-MRS acquisition
      collected spectral data from a 4 * 4 cluster of voxels acquired in the axial
      plane encompassing the subcortical structures as well as frontal-temporal
      cortical gray and white matter. The slab thickness was 3 cm and the approximate
      total volume of brain sampled was 432 cm(3) . The spectra obtained were analyzed
      using a fully automated in-house fitting algorithm. A population-averaged
      generalized estimating equation was used to evaluate changes both in
      phosphomonoesters (PME) [phosphocholine (PCho) and phosphoethanolamine (PEtn)]
      and phosphodiesters (PDE) [glycerophosphocholine (GPCho) and
      glycerophosphethanolamine (GPEtn)]. Metabolite ratios were reported with respect
      to the total integrated (31) P resonance area. RESULTS:   The uridine group had
      significantly increased total PME and PEtn levels over the one-week period [6.32
      and 7.17% for PME and PEtn, respectively (p<0.001)]. Other metabolite levels such
      as PCho, PDE, GPEtn and GPCho showed no significant changes following either
      uridine or placebo (all p>0.05). CONCLUSIONS:   This is the first study to report
      a direct effect of uridine on membrane phospholipid precursors in healthy adults
      using (31) P-MRS. Sustained administration of uridine appears to increase PME in
      healthy subjects. Further investigation is required to clarify the effects of
      uridine in disorders with altered phospholipid metabolism such as bipolar
      disorder.

PMID- 21176031
TI  - Social competence and observer-rated social functioning in bipolar disorder.
AB  - OBJECTIVE:   Impairment in social functioning appears to be common in bipolar
      disorder, although estimates have been derived largely from self-report measures.
      We examined performance-based and observer-based ratings of social competence and
      functioning and assessed the contribution of symptoms and neurocognitive ability
      to social functioning in bipolar disorder. METHODS:   In this cross-sectional
      study, 164 subjects with bipolar disorder were administered the performance-based
      Social Skills Performance Assessment (SSPA), rated by an informant on the
      Specific Level of Functioning (SLOF)-Interpersonal subscale, received clinical
      ratings of depression and manic symptoms, and performed neurocognitive tests. We
      assessed the proportion of patients exhibiting social deficits and examined the
      associations between composite measures of neurocognitive ability, depression and
      manic symptoms, and SSPA scores with informant-rated, real-world social
      functioning. RESULTS:   Mean age of the sample was 47.6 years (SD = 14.1).
      Subjects were experiencing, on average, mild levels of depression and minimal
      manic symptoms. A total of 29% exhibited norm-referenced impairment on the SSPA,
      and 64% registered at least one impairment on SLOF items; unemployed subjects had
      lower SSPA and SLOF ratings. Neurocognitive performance correlated with both
      performance-based and observer-rated social functioning, whereas depressive and
      manic symptoms correlated only with observer-rated social impairments. In
      multivariate models, depression was the most potent association with social
      functioning, and impairment in social competence (i.e., capacity) increased the
      strength of the relationships between depression and neurocognitive impairment
      and social functioning (i.e., real-world functioning). CONCLUSIONS:   Our study
      confirmed the negative relationship of bipolar depression with social
      functioning. A subgroup of outpatients with bipolar disorder has impaired social
      competence, which, when present, worsened the impact of depression and cognitive
      impairment on social functioning.

PMID- 21176033
TI  - One-year post-hospital medical costs and relapse rates of bipolar disorder
      patients in Taiwan: a population-based study.
AB  - OBJECTIVES:   We examined a nationwide population-based dataset of patients with
      bipolar disorder (BD) hospitalized in Taiwan, with our analyses focusing on one
      year medical costs and relapse rates. METHODS:   The data for this study,
      covering the years 2006 and 2007, were obtained from the Taiwan National Health
      Insurance (NHI) claims database. The study sample comprised BD patients who were
      discharged from hospitals between January 1 and December 31, 2006. Annual medical
      costs and relapse rates were described; the Kaplan-Meier method and the
      generalized linear models were carried out to examine the risk factors associated
      with cases of relapse. RESULTS:   The annual medical costs associated with
      relapses among the study sample were found to be approximately 7.6 times the
      average per-capita NHI expenditure in Taiwan in 2006 (US$4,354 versus US$574),
      with a one-year relapse rate of 55%. Those patients between 20 and 60 years old
      with a medication possession ratio of <80 and with depressive episodes during the
      recruitment period were identified as being at risk of relapse. CONCLUSION:  
      Bipolar disorder, which is a very costly disease, is associated with both poor
      medication adherence rates and frequent recurrences. Targeting drug adherence
      issues during maintenance treatment may well provide a valuable opportunity to
      reduce the risk of such recurrences.

PMID- 21176034
TI  - Prefrontal and paralimbic metabolic dysregulation related to sustained attention
      in euthymic older adults with bipolar disorder.
AB  - OBJECTIVE:   Reports of sustained attention deficits in the euthymic phase of
      bipolar disorder have been variable, and have yet to be related to cerebral
      metabolism. In the present study, we evaluated relationships between cognitive
      performance deficits and resting cerebral metabolism in euthymic older adults
      with bipolar disorder. METHODS:   Sixteen older (mean age 58.7 years) euthymic
      outpatients with bipolar disorder (10 type I, 6 type II; 44% female) and 11 age
      matched healthy controls received resting positron emission tomography with (18)
      fluorodeoxyglucose and, within 10 days, the Conners' Continuous Performance Test
      II, a commonly used measure of sustained attention and inhibitory control.
      RESULTS:   Bipolar disorder patients had significantly more omission errors (z =
      2.53, p = 0.01) and a trend toward more commission errors (z = 1.83, p < 0.07)
      than healthy controls. Relative to healthy controls, among bipolar disorder
      subjects commission errors were more strongly related to inferior frontal gyrus
      [Brodmann area (BA) 45/47] hypometabolism and paralimbic hypermetabolism. In
      bipolar disorder subjects, relative to controls, omission errors were more
      strongly related to dorsolateral prefrontal (BA 9/10) hypometabolism and greater
      paralimbic, insula, and cingulate hypermetabolism. CONCLUSIONS:   In older adults
      with bipolar disorder, even during euthymia, resting-state corticolimbic
      dysregulation was related to sustained attention deficits and inhibitory control,
      which could reflect the cumulative impact of repeated affective episodes upon
      cerebral metabolism and neurocognitive performance. The relative contributions of
      aging and recurrent affective episodes to these differences in bipolar disorder
      patients remain to be established.

PMID- 21176032
TI  - The relationship of bipolar disorder lifetime duration and vascular burden to
      cognition in older adults.
AB  - OBJECTIVES:   We describe the cognitive function of older adults presenting with
      bipolar disorder (BD) and mania and examine whether longer lifetime duration of
      BD is associated with greater cognitive dysfunction. We also examine whether
      there are negative, synergistic effects between lifetime duration of BD and
      vascular disease burden on cognition. METHODS:   A total of 87 nondemented
      individuals with bipolar I disorder, age 60 years and older, experiencing manic,
      hypomanic, or mixed episodes, were assessed with the Dementia Rating Scale (DRS)
      and the Framingham Stroke Risk Profile (FSRP) as a measure of vascular disease
      burden. RESULTS:   Subjects had a mean (SD) age of 68.7 (7.1) years and 13.6
      (3.1) years of education; 50.6% (n = 44) were females, 89.7% (n = 78) were white,
      and 10.3% (n = 9) were black. They presented with overall and domain-specific
      cognitive impairment in memory, visuospatial ability, and executive function
      compared to age-adjusted norms. Lifetime duration of BD was not related to DRS
      total score, any other subscale scores, or vascular disease burden. FSRP scores
      were related to the DRS memory subscale scores, but not total scores or any other
      domain scores. A negative interactive effect between lifetime duration of BD and
      FSRP was only observed with the DRS construction subscale. CONCLUSIONS:   In this
      study, lifetime duration of BD had no significant relationship with overall
      cognitive function in older nondemented adults. Greater vascular disease burden
      was associated with worse memory function. There was no synergistic relationship
      between lifetime duration of BD and vascular disease burden on overall cognition
      function. Addressing vascular disease, especially early in the course of BD, may
      mitigate cognitive impairment in older age.

PMID- 21176035
TI  - Association of Per3 gene with bipolar disorder: comment on "Association study of
      21 circadian genes with bipolar I disorder, schizoaffective disorder, and
      schizophrenia".

PMID- 21176038
TI  - Amniotic membrane transplantation for Mooren's ulcer.
AB  - BACKGROUND: To describe the outcome of surgery using amniotic membrane
      transplantation for Mooren's ulcer. DESIGN: A prospective interventional case
      series from the Vietnam National Institute of Ophthalmology. PARTICIPANTS:
      Eighteen eyes of 14 patients with Mooren's ulcer. Seven eyes had recurrent
      episodes of ulceration, and 11 were not responsive to medical therapy or
      conjunctival resection. METHODS: All eyes were treated with amniotic membrane
      grafts for Mooren's ulcer (10 eyes with multilayer grafts; 8 with a single layer
      graft). Five eyes with a 360 degrees  peripheral ulcer were treated with an
      overlay amniotic membrane graft, and 13 eyes were treated with a freehand graft
      tailored to fit the localized defect. MAIN OUTCOME MEASURES: Time to epithelial
      healing. Visual acuity outcome. RESULT: Sixteen of 18 eyes were treated by a
      single surgery with amniotic membrane with rapid healing of the epithelial defect
      (mean time to complete epithelialization 12.4 days). Two eyes required a second
      amniotic membrane graft: one eye required regrafting following a subgraft
      haemorrhage and another eye required regrafting for a persistent epithelial
      defect. Vision was stabilized in all eyes with 10 of 18 eyes obtaining vision of
      6/12 or better. CONCLUSION: Amniotic membrane transplantation may be a useful
      treatment for selected patients with Mooren's ulcer especially where systemic
      immunosuppressive drugs are unavailable.

PMID- 21176037
TI  - Phosphoinositides direct equine infectious anemia virus gag trafficking and
      release.
AB  - Phosphatidylinositol 4,5-biphosphate [PI(4,5)P(2) ], the predominant
      phosphoinositide (PI) on the plasma membrane, binds the matrix (MA) protein of
      human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus
      (EIAV) with similar affinities in vitro. Interaction with PI(4,5)P(2) is critical
      for HIV-1 assembly on the plasma membrane. EIAV has been shown to localize in
      internal compartments; hence, the significance of its interaction with
      PI(4,5)P(2) is unclear. We therefore investigated the binding in vitro of other
      PIs to EIAV MA and whether intracellular association with compartments bearing
      these PIs was important for assembly and release of virus-like particles (VLPs)
      formed by Gag. In vitro, EIAV MA bound phosphatidylinositol 3-phosphate [PI(3)P]
      with higher affinity than PI(4,5)P(2) as revealed by nuclear magnetic resonance
      (NMR) spectra upon lipid titration. Gag was detected on the plasma membrane and
      in compartments enriched in phosphatidylinositol 3,5-biphosphate [PI(3,5)P(2) ].
      Treatment of cells with YM201636, a kinase inhibitor that blocks production of
      PI(3,5)P(2) from PI(3)P, caused Gag to colocalize with aberrant compartments and
      inhibited VLP release. In contrast to HIV-1, release of EIAV VLPs was not
      significantly diminished by coexpression with 5-phosphatase IV, an enzyme that
      specifically depletes PI(4,5)P(2) from the plasma membrane. However, coexpression
      with synaptojanin 2, a phosphatase with broader specificity, diminished VLP
      production. PI-binding pocket mutations caused striking budding defects, as
      revealed by electron microscopy. One of the mutations also modified Gag-Gag
      interaction, as suggested by altered bimolecular fluorescence complementation. We
      conclude that PI-mediated targeting to peripheral and internal membranes is a
      critical factor in EIAV assembly and release.

PMID- 21176039
TI  - Microbial keratitis in Waikato, New Zealand.
AB  - BACKGROUND: Bacterial keratitis is a potentially sight-threatening condition.
      This study is performed to identify the common causative organisms for bacterial
      keratitis in Waikato region and the antibiotic sensitivities to these organisms.
      DESIGN: Retrospective, observational, case series. PARTICIPANTS: The microbiology
      records of all patients with bacterial keratitis who presented to the
      Ophthalmology department, Waikato Hospital, New Zealand between January 2003 and
      December 2007. METHODS: The corneal scrape results were reviewed. Antibiotic
      sensitivity for the organism was tested following National Committee for Clinical
      Laboratory Standards (NCCLS) method. MAIN OUTCOME MEASURES: In vitro laboratory
      susceptibility testing of ocular isolates to various antibiotics. RESULTS: A
      total of 265 scrapes were performed. Gram stain was positive in 35 (13.2%) eyes.
      Positive culture was seen in 174 (65.6%) scrapes; 78.2% were Gram-positive and
      20.2% were Gram-negative organisms. Most common Gram-positive organisms were
      coagulase-negative Staphylococci (40.8%) and Staphylococcus aureus (11.5%). Most
      common Gram-negative organisms were Moraxalla species (8.0%) and Pseudomonas
      aeroginosa (3.4%). Of the bacterial organisms 99% were sensitive to
      ciprofloxacin. All Gram-negative organisms and 95.5% Gram-positive organisms were
      sensitive to tobramycin; 96.6% Gram-positive organisms and 98.3% Gram-negative
      organisms were sensitive to cefuroxime. CONCLUSIONS: Our results are comparable
      to other regions in New Zealand but the incidence of coagulase-negative
      Staphylococcus is much higher in this region compared with other New Zealand
      studies. It seems appropriate to start patients with corneal ulcers initially on
      fluoroquinolone monotherapy while awaiting culture results.

PMID- 21176040
TI  - Intermediate-term results of the Ex-PRESS miniature glaucoma implant under a
      scleral flap in previously operated eyes.
AB  - BACKGROUND: To report the safety and efficacy of Ex-PRESS(TM) miniature glaucoma
      implant under a scleral flap in patients with previous ocular surgeries. DESIGN:
      Retrospective, non-comparative case series from a tertiary care hospital.
      PARTICIPANTS: Patients with previous cataract or failed glaucoma surgeries who
      had undergone implantation of the Ex-PRESS(TM) miniature glaucoma implant (R-50
      and T-50), under a scleral flap, with a minimum of 1-year postoperative follow
      up. METHODS: For postoperative outcome, success was defined as complete if
      intraocular pressure (IOP) was 5-21 mmHg without medication or surgical
      intervention, and qualified if intraocular pressure was within the same range
      with glaucoma medication. To compare the outcome between patients who had
      previous trabeculectomy or cataract surgery the definition of success was
      intraocular pressure of 5-15 mmHg. MAIN OUTCOME MEASURES: Intraocular pressure,
      number of antiglaucoma drugs, visual acuity and complications. RESULTS: One
      hundred eyes (100 patients; mean age: 77.4 years) with a mean follow-up period of
      27 +/- 13.2 months (range: 12-66) were considered. Success was complete in 60
      (60%) and qualified in 24 (24%) eyes. The mean preoperative IOP of 27.7 +/- 9.2
      mmHg (range: 14-52 mmHg) with 2.73 +/- 1.1 drugs declined to 14.02 +/- 5.1 mmHg
      with 0.72 +/- 1.06 drugs at the last follow up (P < 0.0001). Causes of failure
      were uncontrolled intraocular pressure (11%), bleb needling (4%) and persistent
      hypotony (1%). The probability of success in the patients with previous cataract
      surgery and trabeculectomy at 3 years was 60.6% and 50.9%, respectively.
      CONCLUSIONS: The Ex-PRESS(TM) implant under scleral flap was a safe and effective
      glaucoma surgery in the eyes with prior ocular surgery.

PMID- 21176042
TI  - Local anaesthesia for trans-scleral cyclodiode laser procedures: surgeon and
      patient satisfaction with sub-Tenon's and peribulbar anaesthesia.

PMID- 21176041
TI  - Period prevalence and incidence of optic disc haemorrhage in normal tension
      glaucoma and primary open-angle glaucoma.
AB  - BACKGROUND: To investigate and compare the period prevalences and incidences of
      optic disc haemorrhages in normal tension glaucoma and primary open-angle
      glaucoma. DESIGN: Hospital-based retrospective study. PARTICIPANTS: Four hundred
      and four patients with normal tension glaucoma and 210 patients with primary open
      angle glaucoma that underwent consecutive disc examinations at least quarterly
      for at least 1 year and stereoscopic optic disc photographs at intervals of 6 to
      12 months between 1992 and 2007. METHODS: The period prevalence of disc
      haemorrhages, gender predominance among patients with disc haemorrhage, and
      cumulative incidence of normal tension glaucoma and primary open-angle glaucoma
      were compared. MAIN OUTCOME MEASURES: Period prevalence, cumulative incidence,
      and gender predominance of DHs in patients with NTG and POAG. RESULTS: Three
      hundred and eighty-seven patients (387 eyes) of normal tension glaucoma patients
      and 205 patients (205 eyes) of primary open-angle glaucoma patients were finally
      enrolled in the study. The period prevalence and incidence rates of the
      stereoscopic optic disc photograph-confirmed glaucomatous disc haemorrhages were
      33.3% (129/387), 0.46 +/- 0.18 times/year in the normal tension glaucoma group,
      and 17.6% (36/205), 0.34 +/- 0.23 times/year in the primary open-angle glaucoma
      group, respectively. The absolute values and ratios of primary open-angle
      glaucoma and normal tension glaucoma in period prevalences and incidence rates in
      the present study were higher than in previous studies. No significant difference
      in gender ratios was found between patients that did or did not develop disc
      haemorrhage for both types of open-angle glaucoma (P > 0.05, respectively).
      CONCLUSIONS: The primary open-angle glaucoma group had higher period prevalences
      and incidence rates of disc haemorrhage than those reported previously. Disc
      haemorrhages were found to develop independent of gender.

PMID- 21176043
TI  - New surgical technique for correcting tube-iris touch following glaucoma drainage
      implant surgery.
AB  - Glaucoma drainage implant surgery may be associated with a number of potential
      complications including tube malpositioning. This malpositioning may have serious
      sequelae such as corneal endothelial damage, chronic iritis, cataract formation
      or tube occlusion. Traditional management of tube malpositioning involves major
      surgical re-dissection and reinsertion of the tube. Alternatively, shortening of
      the tube within the anterior chamber can, in some circumstances, relieve tube
      contact with the endothelium or iris. However, these procedures are associated
      with important risks. We describe a new minimally invasive surgical technique for
      correcting posterior tube malpositioning that avoids the need to shorten the tube
      or re-dissect the conjunctiva. This technique is straightforward to perform and
      has successfully maintained proper drainage device tube position during more than
      1 year of follow up.

PMID- 21176044
TI  - Caspase inhibitors protect against NMDA-mediated retinal ganglion cell death.
AB  - BACKGROUND: Apoptosis is a major mechanism of cell death in glutamate-induced
      excitotoxicity and caspases as the executors of apoptosis play an important role
      in the development of various central nervous system and eye diseases. We studied
      the involvement of certain caspases in excitotoxic retinal ganglion cell death,
      which was experimentally induced in Brown Norway Rats by application of the
      glutamate receptor agonist N-methyl-D-aspartate (NMDA). METHODS: Animals were
      injected intravitreally with one of six caspase inhibitors (against caspases 1,
      3, 4, 6, 8 and 9). Seven hours later, NMDA or phosphate-buffered saline as a
      control was injected intravitreally into the respective eyes. The neuroprotective
      potential against NMDA toxicity was assessed by retinal ganglion cell
      quantification. Additionally, wholemount TUNEL was performed. RESULTS:
      Statistical analysis revealed significant neuroprotective effects for the
      inhibitors of caspases 3, 6, 8 and 9, but not for those of caspases 1 and 4. The
      inhibitors of caspases 6 and 9 showed greater neuroprotective potential than
      those of caspases 3 and 8, although cell death was not entirely averted in any
      case. Results of ganglion cell counts were confirmed for the most pronounced
      treatment groups using wholemount TUNEL. CONCLUSION: Excitotoxic retinal ganglion
      cell death after NMDA injection is mediated mainly through apoptosis, whereby
      extrinsic as well as intrinsic pathways of caspase activation play a role.

PMID- 21176045
TI  - Classification of iris colour: review and refinement of a classification schema.
AB  - Eye colour or, more accurately, iris colour is one of the most obvious physical
      characteristics of a person. European parents frequently ask the colour of their
      newborn's eyes, only to see the iris change dramatically during their child's
      first year of life. Genetic and epidemiological findings have uncovered further
      details about the basis for iris colour, which may have important implications
      for further research and treatment of some eye diseases and ocular
      characteristics. Surprisingly there is no widely recognized classification system
      for eye colour. An added difficulty when trying to devise an international system
      is that subtle differences in colour description exist between languages (e.g.
      hazel vs. auburn). We reviewed the recent and very early literature pertaining to
      eye colour classification. Recent genetic investigations of eye colour have
      tended to either use simple (three-category grading systems) or more complex
      digital colour grading. We present a nine-category grading system. Categories in
      this novel schema include: (i) light blue; (ii) darker blue; (iii) blue with
      brown peripupillary ring; (iv) green; (v) green with brown iris ring; (vi)
      peripheral green central brown; (vii) brown with some peripheral green; (viii)
      brown; and (ix) dark brown. Although different observers may categorize a
      person's eye colour differently, it is generally only by an adjacent category. We
      also describe a continuum of iris pigmentation from a small ring of brown around
      the pupil to almost complete brown with small peripheral flecks. Digital
      publishing and assessment of iris colour will result in more standardized
      classification of iris colour and investigation of its role in eye disease.

PMID- 21176046
TI  - Specific amacrine cell changes in an induced mouse model of glaucoma.
AB  - BACKGROUND: To investigate retinal cell population changes under chronic elevated
      intraocular pressure in an inducible mouse model of glaucoma. METHODS: Chronic
      unilateral ocular hypertension was induced in 40 C57BL6/J mice by ablation of the
      limbal episcleral veins. After 5, 20, 40 and 60 days of elevated intraocular
      pressure, specific retinal cell types were identified and/or quantified by
      immunohistochemistry for protein kinase C alpha, glial fibrillary acidic protein,
      parvalbumin and calretinin. Apoptotic cells were identified by TUNEL and cleaved
      caspase-3 immunohistochemistry. RESULTS: Elevations in intraocular pressure in
      the range 22-30 mmHg were developed and sustained in mice for up to 60 days.
      Protein kinase C alpha immunoreactivity localized to bipolar cells was unchanged.
      We observed a rapid increase in glial fibrillary acidic protein expression in
      Muller cells and a progressive loss of parvalbumin-labelled ganglion cells. After
      60 days of elevated intraocular pressure, calretinin-immunoreactive cell counts
      declined by 55.4% and 46.4% in the inner nuclear and ganglion cell layers,
      respectively. However, at all time points examined, the markers of cell death
      were only observed in the ganglion cell layer, not in the inner nuclear layer.
      CONCLUSIONS: In addition to ganglion cell death and reactive Muller cell changes,
      chronic experimental elevation of intraocular pressure alters calcium-binding
      protein immunohistochemistry in amacrine cells. However, these changes are not
      indicative of amacrine cell loss but may represent early indicators of cellular
      distress that precede physiological dysfunction or cell death.

PMID- 21176047
TI  - Differences in diabetic retinopathy management by primary eye care providers in
      Australia.

PMID- 21176048
TI  - Antimetabolite application technique in trabeculectomy surgery.

PMID- 21176049
TI  - Bilateral subconjunctival emphysema as a complication of pneumothorax.

PMID- 21176051
TI  - Are all seeds equal? Spatially explicit comparisons of seed fall and sapling
      recruitment in a tropical forest.
AB  - Understanding demographic transitions may provide the key to explain the high
      diversity of tropical tree communities. In a faunally intact Amazonian forest, we
      compared the spatial distribution of saplings of 15 common tree species with
      patterns of conspecific seed fall, and examined the seed-to-sapling transition in
      relation to locations of conspecific trees. In all species, the spatial pattern
      of sapling recruitment bore no resemblance to predicted distributions based on
      the density of seed fall. Seed efficiency (the probability of a seed producing a
      sapling) is strongly correlated with distance from large conspecific trees, with
      a >30-fold multiplicative increase between recruitment zones that are most
      distant vs. proximal to conspecific adults. The striking decoupling of sapling
      recruitment and conspecific seed density patterns indicates near-complete
      recruitment failure in areas of high seed density located around reproductive
      adults. Our results provide strong support for the spatially explicit predictions
      of the Janzen-Connell hypothesis.

PMID- 21176050
TI  - Enhanced root exudation induces microbial feedbacks to N cycling in a pine forest
      under long-term CO2 fumigation.
AB  - The degree to which rising atmospheric CO(2) will be offset by carbon (C)
      sequestration in forests depends in part on the capacity of trees and soil
      microbes to make physiological adjustments that can alleviate resource
      limitation. Here, we show for the first time that mature trees exposed to CO(2)
      enrichment increase the release of soluble C from roots to soil, and that such
      increases are coupled to the accelerated turnover of nitrogen (N) pools in the
      rhizosphere. Over the course of 3 years, we measured in situ rates of root
      exudation from 420 intact loblolly pine (Pinus taeda L.) roots. Trees fumigated
      with elevated CO(2) (200 p.p.m.v. over background) increased exudation rates (MUg
      C cm(-1) root h(-1) ) by 55% during the primary growing season, leading to a 50%
      annual increase in dissolved organic inputs to fumigated forest soils. These
      increases in root-derived C were positively correlated with microbial release of
      extracellular enzymes involved in breakdown of organic N (R(2) = 0.66; P = 0.006)
      in the rhizosphere, indicating that exudation stimulated microbial activity and
      accelerated the rate of soil organic matter (SOM) turnover. In support of this
      conclusion, trees exposed to both elevated CO(2) and N fertilization did not
      increase exudation rates and had reduced enzyme activities in the rhizosphere.
      Collectively, our results provide field-based empirical support suggesting that
      sustained growth responses of forests to elevated CO(2) in low fertility soils
      are maintained by enhanced rates of microbial activity and N cycling fuelled by
      inputs of root-derived C. To the extent that increases in exudation also
      stimulate SOM decomposition, such changes may prevent soil C accumulation in
      forest ecosystems.

PMID- 21176052
TI  - Diversity, biological roles and biosynthetic pathways for sugar-glycerate
      containing compatible solutes in bacteria and archaea.
AB  - A decade ago the compatible solutes mannosylglycerate (MG) and glucosylglycerate
      (GG) were considered to be rare in nature. Apart from two species of thermophilic
      bacteria, Thermus thermophilus and Rhodothermus marinus, and a restricted group
      of hyperthermophilic archaea, the Thermococcales, MG had only been identified in
      a few red algae. Glucosylglycerate was considered to be even rarer and had only
      been detected as an insignificant solute in two halophilic microorganisms, a
      cyanobacterium, as a component of a polysaccharide and of a glycolipid in two
      actinobacteria. Unlike the hyper/thermophilic MG-accumulating microorganisms,
      branching close to the root of the Tree of Life, those harbouring GG shared a
      mesophilic lifestyle. Exceptionally, the thermophilic bacterium Persephonella
      marina was reported to accumulate GG. However, and especially owing to the
      identification of the key-genes for MG and GG synthesis and to the escalating
      numbers of genomes available, a plethora of new organisms with the resources to
      synthesize these solutes has been recognized. The accumulation of GG as an
      'emergency' compatible solute under combined salt stress and nitrogen-deficient
      conditions now seems to be a disseminated survival strategy from enterobacteria
      to marine cyanobacteria. In contrast, the thermophilic and extremely radiation
      resistant bacterium Rubrobacter xylanophilus is the only actinobacterium known to
      accumulate MG, and under all growth conditions tested. This review addresses the
      environmental factors underlying the accumulation of MG, GG and derivatives in
      bacteria and archaea and their roles during stress adaptation or as precursors
      for more elaborated macromolecules. The diversity of pathways for MG and GG
      synthesis as well as those for some of their derivatives is also discussed. The
      importance of glycerate-derived organic solutes in the microbial world is only
      now being recognized. Their stress-dependent accumulation and the molecular
      aspects of their interactions with biomolecules have already fuelled several
      emerging applications in biotechnology and biomedicine.

PMID- 21176053
TI  - Genomic insights into the metabolic potential of the polycyclic aromatic
      hydrocarbon degrading sulfate-reducing Deltaproteobacterium N47.
AB  - Anaerobic degradation of polycyclic aromatic hydrocarbons (PAHs) is an important
      process during natural attenuation of aromatic hydrocarbon spills. However,
      knowledge about metabolic potential and physiology of organisms involved in
      anaerobic degradation of PAHs is scarce. Therefore, we introduce the first genome
      of the sulfate-reducing Deltaproteobacterium N47 able to catabolize naphthalene,
      2-methylnaphthalene, or 2-naphthoic acid as sole carbon source. Based on
      proteomics, we analysed metabolic pathways during growth on PAHs to gain
      physiological insights on anaerobic PAH degradation. The genomic assembly and
      taxonomic binning resulted in 17 contigs covering most of the sulfate reducer N47
      genome according to general cluster of orthologous groups (COGs) analyses.
      According to the genes present, the Deltaproteobacterium N47 can potentially grow
      with the following sugars including d-mannose, d-fructose, d-galactose, alpha-d
      glucose-1P, starch, glycogen, peptidoglycan and possesses the prerequisites for
      butanoic acid fermentation. Despite the inability for culture N47 to utilize
      NO(3) (-) as terminal electron acceptor, genes for nitrate ammonification are
      present. Furthermore, it is the first sequenced genome containing a complete TCA
      cycle along with the carbon monoxide dehydrogenase pathway. The genome contained
      a significant percentage of repetitive sequences and transposase-related protein
      domains enhancing the ability of genome evolution. Likewise, the sulfate reducer
      N47 genome contained many unique putative genes with unknown function, which are
      candidates for yet-unknown metabolic pathways.

PMID- 21176054
TI  - Ribosomal tag pyrosequencing of DNA and RNA from benthic coral reef microbiota:
      community spatial structure, rare members and nitrogen-cycling guilds.
AB  - Ribosomal tag libraries based on DNA and RNA in coral reef sediment from Hawaii
      show the microbial community to be dominated by the bacterial phyla
      Proteobacteria, Firmicutes and Actinobacteria, the archaeal order
      Nitrosopumilales and the uncultivated divisions Marine Group III (Euryarchaeota)
      and Marine Benthic Group C (Crenarchaeota). Operational taxonomic units (OTUs)
      number in the high thousands, and richness varies with site, presence or absence
      of porewater sulfide (sediment depth), and nucleotide pool. Rank abundance curves
      of DNA-based libraries, but not RNA-based libraries, possess a tail of low
      abundance taxa, supporting the existence of an inactive 'rare' biosphere. While
      bacterial libraries from two oxic samples differ markedly, those from two anoxic
      (sulfidic) samples are similar. The four dominant bacterial OTUs are members of
      genera that include pathogens, but are found in marine environments, and include
      facultative anaerobes, i.e. dissimilatory nitrate reducers and denitrifiers. This
      may explain their abundance in both oxic and anoxic samples. A numerous archaeon
      is closely related to the lithoautotrophic ammonia oxidizer Nitrosopumilus
      maritimus. Known bacterial ammonia oxidizers are essentially absent, but
      bacterial nitrite oxidizers are abundant. Although other studies of this reef
      found evidence for anaerobic ammonia oxidizers, primer bias rendered that clade
      invisible to this study.

PMID- 21176055
TI  - Ectomycorrhizal roots select distinctive bacterial and ascomycete communities in
      Swedish subarctic forests.
AB  - Ectomycorrhizal (ECM) roots represent important niches for interactions with
      bacteria and ascomycete fungi, since they have a large surface area and receive a
      direct supply of plant assimilates from their tree hosts. We tested the
      hypothesis that the roots colonized by specific ECM fungi harbour distinct
      bacteria/ascomycete communities. Roots were collected from two different
      locations in a subarctic shrub forest dominated by Betula pubescens. Bacterial
      and ascomycete communities were analysed by PCR-DGGE and sequencing, in roots
      colonized by five frequently observed ECM fungi, Leccinum variicolor, Piloderma
      fallax, Tomentellopsis submollis, Lactarius torminosus and Pseudotomentella
      tristis. The bacterial communities associated with P. fallax- or P. tristis
      colonized roots were distinct from those associated with roots colonized by three
      other ECM fungi at both sampling locations. Bacterial communities associated with
      T. submollis-, L. torminosus- and L. variicolor-colonized roots were more similar
      to each other. Lactarius- and Pseudotomentella-colonized roots hosted distinct
      ascomycete communities at one site while only the community associated with
      Lactarius was distinct at the second location. The results thus suggest that
      while the community structure of bacteria colonizing ECM roots can be influenced
      by the local soil environment, there can also be a strong selective effect of
      particular fungal symbionts.

PMID- 21176056
TI  - Cyclic nucleotide signalling in malaria parasites.
AB  - Cyclic nucleotides are so-called intracellular second messenger molecules used by
      all cells to transform environmental signals into an appropriate response.
      Interest in the cyclic nucleotides cAMP and cGMP in malaria parasites followed
      early observations that both molecules might be involved in distinct
      differentiation events within the sexual phase of the life cycle that is required
      for transmission of parasites to the mosquito vector. Completed genome sequences
      combined with biochemical and genetic studies have confirmed the presence of the
      main enzymatic components of cyclic nucleotide signalling in the parasite.
      Dissection of their functions is underway and is giving initial insights into
      some of the cellular processes, which are regulated by these signalling pathways.
      Malaria parasites occupy terminally differentiated red blood cells for a
      significant proportion of their life cycle, but although there is some evidence
      of potential roles for the residual host cell signalling machinery in parasite
      development, details are few. A major gap in our knowledge is the nature of the
      cell surface receptors, which might trigger cyclic nucleotide signalling in the
      parasite.

PMID- 21176057
TI  - Clinical implications of acellular mucin pools in resected rectal cancer with
      pathological complete response to neoadjuvant chemoradiation.
AB  - AIM: Approximately 20% of rectal cancers treated with neoadjuvant chemoradiation
      achieve a pathological complete response (pCR), which is associated with an
      improved oncological outcome. However, in a proportion of patients with a pCR,
      acellular pools of mucin are present in the surgical specimen. The aim of this
      study was to evaluate the clinical implications of acellular mucin pools in
      patients with rectal adenocarcinoma achieving a pCR after neoadjuvant
      chemoradiation followed by proctectomy. METHOD: A single-centre colorectal cancer
      database was searched for patients with clinical Stage II and Stage III rectal
      adenocarcinoma who achieved a pCR (i.e. ypT0N0M0) after neoadjuvant
      chemoradiation followed by proctectomy between 1997 and 2007. Patients were
      categorized according to the presence or absence of acellular mucin pools in the
      resected specimen, and groups were compared. Patient demographics, tumour and
      treatment characteristics, and oncological outcomes were recorded. Primary
      outcomes were 3-year local and distant recurrences, and disease-free and overall
      survivals. RESULTS: Two hundred and fifty-eight patients with clinical Stage II
      or Stage III rectal adenocarcinoma were treated by neoadjuvant chemoradiation.
      Fifty-eight of these patients had a 58 pCR. Eleven of the 58 patients with a pCR
      had acellular mucin pools in the surgical specimen. The median follow up was 40
      months. The groups were statistically similar with respect to demographics,
      chemoradiation regimens, distance of tumour from the anal verge, clinical stage
      and surgical procedure. No patient had local recurrence. Patients with acellular
      mucin pools had increased distant recurrence (21%vs 5%), decreased disease-free
      survival (79%vs 95%) and decreased overall survival (83%vs 95%) rates, although
      none of these differences was statistically significant. CONCLUSION: The presence
      of acellular mucin pools in a proctectomy specimen with a pCR does not affect
      local recurrence, but may suggest a more aggressive tumour biology.

PMID- 21176059
TI  - Polyethylene glycol and constipation treatment.

PMID- 21176060
TI  - Cross-matched blood in colorectal surgery: a clinical waste?
AB  - AIM: This study was carried out to determine the rate of perioperative blood
      transfusion and to create an evidence-based approach to requesting blood for
      elective colorectal surgery. METHOD: A comparative cohort study was carried out
      of 164 patients (107 men, 57 women, median age 68 years) who underwent major
      colorectal surgery. Details obtained included demographic and operative
      information, the number of units of blood cross-matched, units used, the reasons
      for transfusion and patient suitability for electronic issue (EI). The cross
      match to transfusion ratio (C:T ratio) was calculated for each procedure and for
      the whole group of colorectal procedures. RESULTS: Some 162 units of blood were
      cross-matched for 76 (46%) patients, with the remaining 88 (54%) being grouped
      with serum saved. Twenty-one (13%) were transfused with a total of 48 units of
      blood. The C:T ratio for all procedures was 3.4/1. The commonest indication for
      transfusion was anaemia. One patient required an emergency transfusion. The
      majority (78%) of patients were suitable for EI. There were no significant
      differences between the transfused and nontransfused groups with regard to age,
      diagnosis (malignant vs benign) and laparoscopic or open colorectal procedure.
      CONCLUSION: Only a small proportion of patients undergoing elective major
      colorectal surgery require perioperative blood transfusions, most of which are
      nonurgent. Blood should not be routinely cross-matched in patients who are
      suitable for EI.

PMID- 21176061
TI  - Does long-course radiotherapy influence postoperative perineal morbidity after
      abdominoperineal resection of the rectum for cancer?
AB  - AIM: The aim of the study was to define risk factors for perineal wound
      complications after abdominoperineal resection (APR), with particular reference
      to preoperative radiotherapy. METHOD: Patients undergoing APR at our institution
      between 1985 and 2009 were reviewed. Wound complications were classified
      according to the Center for Disease Control and Prevention classification of
      surgical site infection (SSI). Perineal complications were identified in patients
      who had preoperative long-course radiotherapy (Group 1) and those who had surgery
      alone (Group 2). RESULTS: One hundred and fifty-seven patients met the inclusion
      criteria. Preoperative radiotherapy was performed in 68 (44.7%) patients (Group
      1), and 89 (65.3%) patients (Group 2) underwent surgery alone. The overall rate
      of perineal wound complications was 14.8%. The wound infection rate was similar
      in each group (Group 1, 10/68, 14.7%; Group 2, 13/89, 14.9%; P = 0.9). An
      elevated BMI (>30) was the only factor correlated with perineal morbidity on
      univariate analysis (P = 0.01). CONCLUSION: Preoperative radiotherapy does not
      influence perineal healing other than in patients with obesity.

PMID- 21176062
TI  - Quality of life, health-related quality of life and health status in patients
      having restorative proctocolectomy with ileal pouch-anal anastomosis for
      ulcerative colitis: a systematic review.
AB  - AIM: There are numerous studies on quality of life (QoL), health-related quality
      of life (HRQoL), and health status (HS) in patients undergoing surgery for
      ulcerative colitis. A systematic review of published literature was conducted to
      establish the quality of these studies and to determine QoL, HRQoL, and HS in
      patients after ileal pouch-anal anastomosis for ulcerative colitis. METHOD: All
      published studies describing QoL, HRQoL, and HS in adult patients in combination
      with ileal pouch-anal anastomosis for ulcerative colitis were reviewed
      systematically. No time or language limitations were applied. Relevance was
      established on the basis of three pre-specified selection criteria: 1) ileal
      pouch-anal anastomosis was performed for ulcerative colitis, 2) QoL, HRQoL, and
      HS were reported as outcome of the study and 3) studies reported a minimum follow
      up after surgery for 12 months. Outcome variables were results of QoL, HRQoL, and
      HS, characteristics of the study population, pouch construction, duration of
      follow-up, and time of assessment in months before and after restorative surgery.
      Descriptive data synthesis was performed by tabulation displaying the
      methodological quality, study characteristics and conclusions on QoL, HRQoL, and
      HS measurements in the studies. RESULTS: The review included 33 studies
      comprising 4790 patients. Three were graded to be of high quality, 23 of moderate
      quality and seven of low quality. All reported improved HS and the majority
      reported improved HRQoL. However, none of the studies reported on QoL.
      CONCLUSION: The HRQoL and HS of patients with ulcerative colitis improved 12
      months after restorative proctocolectomy with an ileal pouch-anal anastomosis and
      were indistinguishable from the HRQoL and HS of the normal healthy population.

PMID- 21176063
TI  - Trends in incidence, treatment and survival of patients with stage IV colorectal
      cancer: a population-based series.
AB  - AIM: The incidence, patterns of care and survival were determined in patients
      with stage IV colorectal cancer (CRC) in a population-based series. METHOD:
      Computer records for patients diagnosed with stage IV CRC diagnosed from 1
      January 1995 to 31 December 2007 were retrieved from the Rotterdam Cancer
      Registry. Surgical resection of the primary tumour, chemotherapy use, hepatic
      surgery and survival were evaluated according to year of diagnosis, age, gender
      and primary tumour site. RESULTS: In the southwestern part of the Netherlands, 19
      014 new patients with CRC were diagnosed and synchronous metastatic disease was
      found in 3482 (18%). This proportion increased during the study period, from 16%
      to 21%. Surgical resection of the primary tumour was performed in approximately
      50% of the patients and did not change over time. Postoperative 30-day mortality
      was 8%. Chemotherapy use increased from 18% in the first period to 56% in the
      latest period. Liver surgery increased from 4% in the first period to 10% in the
      latest period. Median survival increased from 7 months to 12 months and 2-year
      survival increased from 14% to 28%. Two-year survival declined with increasing
      age and was significantly worse for right-sided tumours (14%). CONCLUSION:
      Survival of patients with stage IV CRC has improved over time and this is
      probably a result of the increased use of chemotherapy and the increased numbers
      of patients who underwent hepatic surgery.

PMID- 21176064
TI  - Doppler-guided haemorrhoidal artery ligation in patients with Crohn's disease.
AB  - AIM: The outcome of Doppler-guided haemorrhoidal artery ligation (DGHAL) was
      assessed in patients with Crohn's disease (CD) suffering from grade III
      haemorrhoids. METHOD: A retrospective study was carried out of patients with CD
      and symptomatic Grade III haemorrhoids treated by DGHAL. Perioperative and follow
      up data were retrieved from our database of patients undergoing DGHAL. RESULTS:
      The study included seven men and six women. The mean age was 34 years old. All
      had CD without anorectal involvement. The median duration of haemorrhoidal
      symptoms was 6.3 years. There was no mortality, new incontinence, faecal
      impaction, urinary retention, abscess formation or persistent pain following the
      procedure. Mean pain score based on a visual analogue scale (VAS) decreased from
      2.4 at 24 h postoperatively to 1.6 on the seventh postoperative day. All patients
      had completely recovered by the third postoperative day. At 18 months, three
      (77%) of the patients were asymptomatic and three had recurrent symptoms.
      CONCLUSION: Doppler-guided haemorrhoidal artery ligation is safe and effective in
      treating Grade III haemorrhoids in patients with CD without rectal involvement.

PMID- 21176067
TI  - Initial treatment costs of organ-confined prostate cancer: a general perspective.
AB  - With the increasing prevalence of prostate cancer and evolving methods for the
      definitive treatment of OCPCa, health economic analyses will be critically
      important, albeit difficult to carry out. Preliminary studies point to RPP as the
      most cost-effective treatment for OCPCa. The quickest postoperative recovery, in
      experienced hands, occurs in RARP and RPP, with ORPP having a slightly, but
      statistically in significant, shorter hospital stay. It should be stressed that
      initial treatment costs are not the only important factor in healthcare costs.
      Readmission for early and late complications and the loss of productivity
      resulting from variation in time to return to work, need also to be considered.
      Loss of productivity may also vary in cost between different institutions and
      countries depending upon the proportion of patients employed. Further large-scale
      multicentre studies are necessary to assess this.

PMID- 21176068
TI  - Urethral strictures.
AB  - What's known on the subject? and What does the study add? Urethral strictures are
      common and increasingly common in an ageing population. The treatment is
      controversial and particularly the relative roles of urethrotomy or urethral
      dilatation on the one hand and urethroplasty on the other. This review aims to
      provide a comprehensive overview of the subject including less commonly discussed
      issues such as the history and pathology of stricture disease. We would hope that
      a comprehensive overview of the subject will give a sharper perspective to aid
      the investigation and management of patients with urethral strictures.

PMID- 21176070
TI  - [18F]-fluorocholine positron-emission/computed tomography for lymph node staging
      of patients with prostate cancer: preliminary results of a prospective study.

PMID- 21176072
TI  - Charleston pouch continent cutaneous urinary diversion.

PMID- 21176078
TI  - The role of a leaky epithelium and potassium in the generation of bladder
      symptoms in interstitial cystitis/overactive bladder, urethral syndrome,
      prostatitis and gynaecological chronic pelvic pain.
AB  - The traditional diagnosis of interstitial cystitis (IC) only recognizes the
      severe form of the disease. The far more common early and intermittent phases of
      the disease are not perceived to be part of IC but rather are misdiagnosed as
      urinary tract infection, urethral syndrome, overactive bladder, chronic
      prostatitis, urethritis, or a type of gynecologic pelvic pain (such as
      endometriosis, vulvodynia, or some type of vaginitis). All of these patient
      groups actually suffer from the same bladder disease. This disease results from a
      leaky bladder epithelium and subsequent potassium leakage into the bladder
      interstitium that generates the symptoms of frequency, urgency, pain or
      incontinence in any combination. Robust scientific data now support this
      important concept. These data will be reviewed herein. The conclusions derived
      from these data substantially alter the paradigms for urology and gynecology in
      the generation of frequency, urgency and pelvic pain. All the above-mentioned
      syndromes unite into one primary disease process, lower urinary dysfunction
      epithelium, or LUDE disease, and not the 10 plus syndromes traditionally
      recognized.

PMID- 21176077
TI  - Robotic partial nephrectomy in the setting of prior abdominal surgery.
AB  - OBJECTIVE: * To evaluate our experience with robotic partial nephrectomy in
      patients with previous abdominal surgery and evaluate the effect of previous
      abdominal surgery on perioperative outcomes. We also describe a technique for
      intraperitoneal access for patients with prior abdominal surgery utilizing the 8
      mm robotic camera for direct-vision trocar placement. PATIENTS AND METHODS: *
      From a prospective cohort of 197 consecutive patients who underwent robotic renal
      surgery at a single academic institution, a total of 95 patients underwent
      transperitoneal robotic partial nephrectomy (RPN). * Patients with and without
      previous abdominal surgery were compared. Patients with prior abdominal surgery
      were subcategorized into two groups: upper midline or ipsilateral upper quadrant
      scar or lower abdominal, contralateral, or minimally-invasive scar. * Demographic
      and perioperative variables were compared between the surgery and no surgery
      groups. Access was obtained using a Veress needle or Hassan technique. * We
      utilized a technique of direct vision placement of the initial trocar on our 10
      most recent cases, using an 8 mm robotic camera placed through the obturator of
      12 mm clear-tipped trocar. * Lysis of adhesions was performed as needed to allow
      for placement of additional robotic ports. RESULTS: * A total of 95 patients
      underwent transperitoneal RPN, of which 41 (43%) had a history of prior abdominal
      surgery and six had upper midline or ipsilateral upper quadrant scars. * There
      were no statistically significant differences between patients with previous
      abdominal surgery and patients with no previous abdominal surgery in BMI (30.4 vs
      29.4 kg/m(2) ), median tumor size (2.5 cm vs 2.3), median total operative time
      (246 vs 250 min), median warm ischemia time (21 vs 16 min), median EBL (150 vs100
      ml), clinical stage, transfusion rate, or complications. * A total of six
      patients underwent 7 previous upper midline or ipsilateral upper quadrant
      surgeries, including open cholecystectomy-2 patients (33%), open partial
      gastrectomy-2 patients (33%) and exploratory laparotomy-1 patient (17%). *
      Complications in this group were an enterotomy during lysis of adhesions that was
      repaired robotically without sequelae and a mesenteric hematoma during Veress
      needle placement. A total of 35 patients underwent 16 other prior abdominal
      surgeries, including abdominal hysterectomy-10 patients (29%), umbilical/inguinal
      hernia repair-9 patients (26%) and appendectomy-7 patients (20%). There were no
      access related injuries in the 10 cases in which the robotic 8 mm camera was used
      for initial trocar placement. CONCLUSIONS: * Transperitoneal robotic partial
      nephrectomy is feasible in the setting of prior abdominal surgery. The majority
      of these patients can have their procedure performed safely without an increase
      in complications. * Direct-vision intraperitoneal placement of initial trocar may
      be achieved by using an 8 mm robotic camera, without the need to switch between
      conventional and robotic cameras.

PMID- 21176080
TI  - Does the presence of muscularis propria on transurethral resection of bladder
      tumour specimens affect the rate of upstaging in cT1 bladder cancer?
AB  - OBJECTIVE * To determine how the presence of MP on T1 biopsy specimens affects
      the outcome of patients undergoing RC as compared to when no MP is identified in
      the TURBT specimen. PATIENTS AND METHODS: * Patients were retrospectively
      identified from the Columbia University Urologic Oncology Database. * From
      January 1986 to October 2009, 114 patients diagnosed with cT1N0M0 bladder cancer
      who underwent RC within 4 months of their last biopsy were identified. * Patients
      were stratified based on the presence of MP on T1 biopsy, and upstaging was
      defined as any tumor T2 or greater, N+, or M+ at the time of radical cystectomy.
      * The rate of upstaging was assessed using univariate and multivariate regression
      models; Kaplan meier curves were also extrapolated for each cohort to compare
      disease specific and overall survival patterns. RESULTS: * Of the 114 patients
      evaluated in this study, 24 (20.2%) did not have MP on their T1 biopsy before RC.
      The rate of upstaging (>=pT2) stratified by the presence of MP on biopsy was 50%
      and 78%, respectively (p = 0.017). * On univariate analysis, lack of MP on biopsy
      was associated with an increased risk of upstaging (HR 3.52, p = 0.021, CI 1.2
      10.3), however did not reach significance as an independent predictor (HR 2.9, p
      = 0.056, CI 0.97-8.9). * At a mean follow-up of 33.5 months, there was no
      difference in disease specific (p = 0.41) and overall survival (p = 0.68) between
      groups. CONCLUSIONS: * The lack of MP on TURBT for high grade cT1N0M0 bladder
      cancer portends a high likelihood of upstaging at RC, although this risk did not
      translate into a detectable increased risk of disease specific mortality.

PMID- 21176079
TI  - Maintenance therapy with bacillus Calmette-Guerin Connaught strain clearly
      prolongs recurrence-free survival following transurethral resection of bladder
      tumour for non-muscle-invasive bladder cancer.
AB  - OBJECTIVE: * To confirm the recurrence-preventing efficacy and safety of 18-month
      bacillus Calmette-Guerin (BCG) maintenance therapy for non-muscle-invasive
      bladder cancer. PATIENTS AND METHODS: * The enrolled patients had been diagnosed
      with recurrent or multiple non-muscle-invasive bladder cancer (stage Ta or T1)
      after complete transurethral resection of bladder tumours (TURBT). * The patients
      were randomized into three treatment groups: a maintenance group (BCG, 81 mg,
      intravesically instilled once weekly for 6 weeks as induction therapy, followed
      by three once-weekly instillations at 3, 6, 12 and 18 months after initiation of
      the induction therapy), a non-maintenance group (BCG, 81 mg, intravesically
      instilled once weekly for 6 weeks) and an epirubicin group (epirubicin, 40 mg,
      intravesically instilled nine times). The primary endpoint was recurrence-free
      survival (RFS). RESULTS: * Efficacy analysis was performed for 115 of the full
      analysis-set population of 116 eligible patients, including 41 maintenance group
      patients, 42 non-maintenance group patients and 32 epirubicin group patients. *
      At the 2-year median point of the overall actual follow-up period, the final
      cumulative RFS rates in the maintenance, non-maintenance and epirubicin groups
      were 84.6%, 65.4% and 27.7%, respectively. * The RFS following TURBT was
      significantly prolonged in the maintenance group compared with the non
      maintenance group (generalized Wilcoxon test, P= 0.0190). CONCLUSION: * BCG
      maintenance therapy significantly prolonged the post-TURBT RFS compared with BCG
      induction therapy alone or epirubicin intravesical therapy.

PMID- 21176081
TI  - Bipolar energy for transurethral resection of bladder tumours at low-power
      settings: initial experience.
AB  - Study Type - Therapy (case series). LEVEL OF EVIDENCE: 4. OBJECTIVE: To evaluate
      the efficacy and safety of using bipolar energy at low-power setting for
      transurethral resection (TUR) of bladder tumours. MATERIALS AND METHODS: In
      total, 108 patients (100 males and eight females) with superficial bladder
      carcinoma undergoing bipolar TUR of bladder tumours (B-TURBT) with the Gyrus(TM)
      Plasma kinetic Tissue Management System (Gyrus Medical Ltd, Cardiff, UK) were
      studied. The initial ten patients were operated at a default setting of 160 W
      cutting and 80 W coagulation. Subsequently, the current settings were modified to
      50 W cutting and 40 W coagulation. The present study reports on the 98 patients
      who underwent TURBT with low-power settings. Tumour number, size, shape,
      location, operating time, hospital stay, blood loss, as well as intraoperative
      and postoperative complications, were all recorded .The resected tissues were
      examined by a pathologist who recorded grade, invasion of the muscularis propria
      and the presence of muscular invasion. RESULTS: Out of the ten patients who were
      operated at the recommended default settings of 160 W cutting and 80 W
      coagulation, three patients had obturator jerks leading to two-bladder
      perforation. The results of 98 patients operated on at the low-power settings of
      50 W cutting and 40 W coagulation are reported. Mean +/- SD age was 56.34 +/-
      13.51 years. Tumours were multiple in 62 (63%) patients and single in 36 (37%)
      patients, with 68 (69%) in the lateral wall and six (6%) involving the ureteric
      orifice. Mean +/- SD tumour size was 2.5 +/- 0.81 cm with a mean +/- SD resection
      time of 36.64 +/- 16.5 min. The mean drop in haemoglobin was 0.94 +/- 0.71 (0.20
      4.0), with a mean +/- SD (range) drop in haematocrit of 1.33 +/- 1.29 (1-7). Five
      (5%) patients required blood transfusion as a result of preoperative low
      haemoglobin. Mean +/- SD drop in sodium was 2.06 +/- 0.66 mEq/L, with no patient
      developing TUR syndrome. None of the 98 patients developed obturator jerks and
      perforation at low-power settings. Complete resection was achieved in 94 (96%)
      patients. Mean postoperative hospital stay was 3 days. CONCLUSIONS: TURBT using
      bipolar energy is safe and effective in the treatment of bladder tumours at power
      settings lower than the conventionally recommended settings. Lower power settings
      reduce the number of obturator jerks and perforations.

PMID- 21176082
TI  - Dimeric naphthoquinones, a novel class of compounds with prostate cancer
      cytotoxicity.
AB  - OBJECTIVES: * To evaluate the cytotoxicity of dimeric naphthoquinones (BiQs) in
      prostate cancer cells. * To assess the interaction of dimeric naphthoquinones
      with common therapies including radiation and docetaxel. MATERIALS AND METHODS: *
      The cytotoxicity of 12 different dimeric naphthoquinones was assessed in androgen
      independent (PC-3, DU-145) and androgen-responsive (LNCaP, 22RV1) prostate cancer
      cell lines and in prostate epithelial cells (PrECs). * BiQ2 and BiQ11 were
      selected for determination of dose response, effects on colony formation and
      initial exploration into mechanism of action. * Synergistic effects with
      radiation and docetaxel were explored using colony-forming and MTT assays.
      RESULTS: * At concentrations of 15uM, BiQ2, BiQ3, BiQ11, BiQ12, and BiQ15
      demonstrated cytotoxicity in all prostate cancer cell lines. * Treatment with
      BiQs limited the ability of prostate cancer cells to form colonies in clonogenic
      assays. * Exposure of prostate cancer to BiQs increased cellular reactive oxygen
      species (ROS), decreased ATP production, and promoted apoptosis. * BiQ
      cytotoxicity was independent of NADP(H):quinone oxidoreductase 1 (NQO1) activity
      in PrECs, PC-3 and 22RV1, but not DU-145 cells. * Exposure of prostate cancer
      cells to radiation before treatment with BiQs increased their activity allowing
      for inhibitory effects well below the IC(50) s of these compounds in PrECs. * Co
      administration of BiQs with docetaxel had minimal additive effects. CONCLUSIONS:
      * Dimeric naphthoquinones represent a new class of compounds with prostate cancer
      cytotoxicity and synergistic effects with radiation. The cytotoxic effect of
      these agents is probably contributed to by the accumulation of ROS and
      mitochondrial dysfunction. * Further studies are warranted to better characterize
      this class of potential chemo-therapeutics.

PMID- 21176083
TI  - Magnetic resonance imaging does not improve the prediction of misclassification
      of prostate cancer patients eligible for active surveillance when the most
      stringent selection criteria are based on the saturation biopsy scheme.
AB  - Study Type - Diagnostic (case series). LEVEL OF EVIDENCE: 4. OBJECTIVE: * To
      investigate the role of magnetic resonance imaging (MRI) in selecting patients
      for active surveillance (AS). PATIENTS AND METHODS: * We identified prostate
      cancers patients who had undergone a 21-core biopsy scheme and fulfilled the
      criteria as follows: prostate-specific antigen (PSA) level <= 10 ng/mL, T1-T2a
      disease, a Gleason score <= 6, <3 positive cores and tumour length per core <3
      mm. * We included 96 patients who underwent a radical prostatectomy (RP) and a
      prostate MRI before surgery. * The main end point of the study was the
      unfavourable disease features at RP, with or without the use of MRI as AS
      inclusion criterion. RESULTS: * Mean age and mean PSA were 62.4 years and 6.1
      ng/mL, respectively. Prostate cancer was staged pT3 in 17.7% of cases. * The rate
      of unfavourable disease (pT3-4 and/or Gleason score >= 4 + 3) was 24.0%. A T3
      disease on MRI was noted in 28 men (29.2%). MRI was not a significant predictor
      of pT3 disease in RP specimens (P = 0.980), rate of unfavourable disease (P =
      0.604), positive surgical margins (P = 0.750) or Gleason upgrading (P = 0.314). *
      In a logistic regression model, no preoperative parameter was an independent
      predictor of unfavourable disease in the RP specimen. * After a mean follow-up of
      29 months, the recurrence-free survival (RFS) was statistically equivalent
      between men with T3 on MRI and those with T1-T2 disease (P = 0.853). CONCLUSION:
      * The results of the present study emphasize that, when the selection of patients
      for AS is based on an extended 21-core biopsy scheme, and uses the most stringent
      inclusion criteria, MRI does not improve the prediction of high-risk and/or non
      organ-confined disease in a RP specimen.

PMID- 21176084
TI  - Is routine indwelling catheterisation of the bladder for caesarean section
      necessary? A systematic review.
AB  - BACKGROUND: Urinary catheterisation, which is associated with 80% of urinary
      tract infections (UTIs), is routinely performed prior to caesarean section
      without justification from the best available research evidence. OBJECTIVES: To
      assess whether it is necessary to place indwelling urinary catheters routinely in
      caesarean section, and to determine the effects of this procedure on UTIs,
      urinary retention, intra-operative difficulties, operative complications, as well
      as other outcomes. SEARCH STRATEGY: MEDLINE, EMBASE, the Cochrane Controlled
      Trials Register, POPLINE, SCI, Chinese Biomedical Literature Database, China
      Academic Journals Full-Text Database and Chinese Scientific Journals Database
      were searched in all languages, together with reference lists of the retrieved
      papers. SELECTION CRITERIA: Randomised controlled trials (RCTs) and nonrandomised
      controlled trials (NRCTs) comparing the use versus nonuse of indwelling urinary
      catheters in caesarean section were included. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently selected the studies and extracted the data. Results from
      the trials were combined to calculate relative risks (RRs) for dichotomous
      outcomes and mean differences (MDs) for continuous outcomes, with 95% confidence
      intervals (CIs). MAIN RESULTS: Three trials (two RCTs and one NRCT) were
      included, involving a total of 1084 participants. Compared with the use of
      indwelling urinary catheters, nonuse had a significantly lower incidence of UTIs
      [RR 0.08; 95% CI 0.01, 0.64 (study design: RCT); RR 0.10; 95% CI 0.02, 0.57
      (study design: NRCT)], a lower rate of discomfort at first voiding (RR 0.06; 95%
      CI 0.03, 0.12), less time until first voiding (MD -16.81; 95% CI -17.31, -16.31)
      and less time until ambulation (MD -6.01; 95% CI -6.68, -5.35); there were no
      statistically significant differences in the rate of urinary retention [RR 5.00;
      95% CI 0.24, 103.18 (study design: RCT); RR 0.74; 95% CI 0.04, 15.18 (study
      design: NRCT)], operating time (MD -1.10; 95% CI -3.32, 1.12) and rate of intra
      operative difficulties (RR 1.00; 95% CI -3.32, 1.12). CONCLUSIONS: The nonuse of
      indwelling urinary catheters in caesarean section is associated with less UTIs
      and no increase in either urinary retention or intra-operative difficulties. Our
      results suggest that the routine use of indwelling urinary catheters for
      caesarean delivery in haemodynamically stable patients is not necessary, and can
      be harmful. However, better and larger randomised trials are needed to confirm
      these findings.

PMID- 21176085
TI  - Dynamic spectral imaging colposcopy: higher sensitivity for detection of
      premalignant cervical lesions.
AB  - OBJECTIVE: to validate the dynamic spectral imaging (DSI) colposcope's colour
      coded map in discriminating high- from low-grade cervical lesions and non
      neoplastic tissue. DESIGN: prospective, comparative, multicentre clinical trial.
      SETTING: the colposcopy clinics of three Dutch hospitals. POPULATION: women of 18
      years or over with an intact cervix, referred for colposcopy. METHODS: during a 3
      minute image acquisition phase, the DSI colposcope was used as a regular video
      colposcope: the colposcopist located and graded potential lesions based on
      conventional colposcopic criteria. Subsequently, a colour-coded map was
      calculated and displayed, representing localisation and severity of the cervical
      lesion. Biopsies were collected from all atypical sites, as identified by digital
      mapping and/or conventional colposcopy. Furthermore, one additional biopsy was
      taken. MAIN OUTCOME MEASURES: histologically confirmed high-grade cervical
      disease (CIN2+). RESULTS: in total 275 women were included in the study: 183
      women were analysed in the 'according-to-protocol' (ATP) cohort and 239 women in
      the 'intention-to-treat' (ITT) cohort. In the ATP cohort, the sensitivity of DSI
      colposcopy to identify women with high-grade (CIN2+) lesions was 79% (95% CI 70
      88) and the sensitivity of conventional colposcopy was 55% (95% CI 44-65) (P =
      0.0006, asymptotic McNemar test). When the DSI colour-coded map was combined with
      conventional colposcopy, the sensitivity was 88% (95% CI 82-95). CONCLUSIONS: DSI
      colposcopy has a significantly higher sensitivity to detect cervical lesions than
      conventional colposcopy. If the colour-coded map is combined with conventional
      colposcopic examination, the sensitivity increases further.

PMID- 21176086
TI  - Administration of misoprostol by trained traditional birth attendants to prevent
      postpartum haemorrhage in homebirths in Pakistan: a randomised placebo-controlled
      trial.
AB  - OBJECTIVE: to determine if misoprostol is safe and efficacious in preventing
      postpartum haemorrhage (PPH) when administered by trained traditional birth
      attendants (TBA) at home deliveries. DESIGN: a randomised, double-blind, placebo
      controlled trial. SETTING: Chitral, Khyber Pakhtunkhwa Province, Pakistan.
      POPULATION: a total of 1119 women giving birth at home. METHODS: from June 2006
      to June 2008, consenting women were randomised to receive 600 microg oral
      misoprostol (n = 534) or placebo (n = 585) after delivery to determine whether
      misoprostol reduced the incidence of PPH (>= 500 ml). MAIN OUTCOME MEASURES: the
      primary outcomes were measured blood loss >= 500 ml after delivery and drop in
      haemoglobin >2 g/dl from before to after delivery. RESULTS: oral misoprostol was
      associated with a significant reduction in the rate of PPH (>= 500 ml) (16.5
      versus 21.9%; relative risk 0.76, 95% CI 0.59-0.97). There were no measurable
      differences between study groups for drop in haemoglobin >2 g/dl (relative risk
      0.79, 95% CI 0.62-1.02); but significantly fewer women receiving misoprostol had
      a drop in haemoglobin >3 g/dl, compared with placebo (5.1 versus 9.6%; relative
      risk 0.53, 95% CI 0.34-0.83). Shivering and chills were significantly more common
      with misoprostol. There were no maternal deaths among participants. CONCLUSIONS:
      postpartum administration of 600 microg oral misoprostol by trained TBAs at home
      deliveries reduces the rate of PPH by 24%. Given its ease of use and low cost,
      misoprostol could reduce the burden of PPH in community settings where universal
      oxytocin prophylaxis is not feasible. Continual training and skill-building for
      TBAs, along with monitoring and evaluation of programme effectiveness, should
      accompany any widespread introduction of this drug.

PMID- 21176087
TI  - Adhesion formation after previous caesarean section-a meta-analysis and
      systematic review.
AB  - BACKGROUND: The optimal technique for performing caesarean section with respect
      to minimising postoperative adhesions has not been determined. OBJECTIVES: To
      evaluate adhesion formation for three common caesarean section techniques in
      women undergoing repeat caesarean section surgeries. SEARCH STRATEGY: A database
      was constructed from Medline, EMBASE, Cochrane Library, National Science Digital
      Library, China Biological Medicine Database and through contact with experts in
      this field from January 1990 to May 2010. SELECTION CRITERIA: Studies were
      included if they examined adhesion formation in repeat caesarean sections as a
      primary objective, delineated a clear study design, specified an adhesion scoring
      system, and had sufficient patient exclusion criteria. DATA COLLECTION AND
      ANALYSIS: We abstracted data regarding adhesion formation. The Mantel-Haenszel
      random-effects model was employed for all analyses using odds ratio or inverse
      variance, along with 95% CI. MAIN RESULTS: Thirty-three qualified studies
      including 4423 women were analysed. There were 406 adhesions among 571 women and
      238 adhesions among 596 women in the Stark's caesarean section (also known as
      Misgav-Ladach method) group and modified Stark's caesarean section group,
      respectively, with pooled OR 4.69 (95% CI 3.32-6.62; P < 0.01, 12 studies); 1173
      adhesions among 1555 women and 1179 adhesions among 1625 women in Stark's
      caesarean section group and classic lower-segment caesarean section group,
      respectively, with pooled odds ratio 1.28 (95% CI 0.97-1.68; P = 0.08, 21
      studies); and 29 adhesions from 102 women and 115 adhesions from 193 women in
      modified Stark's caesarean section group and classic lower-segment caesarean
      section group, respectively, with pooled odds ratio 0.28 (95% CI 0.10-0.82; P =
      0.02, two studies). AUTHORS' CONCLUSIONS: Closure of the peritoneum in modified
      Stark's caesarean section resulted in less adhesion formation and should be
      recommended.

PMID- 21176088
TI  - A new uterine compression suture for postpartum haemorrhage with atony.
AB  - Postpartum haemorrhage (PPH) is a major cause of worldwide maternal mortality and
      is still associated with significant morbidity. After the B-Lynch suture was
      reported in 1997, several different uterine compression sutures were found to be
      successful in controlling PPH. In this paper, we describe another simple
      variation of the uterine compression suture technique, which was performed
      without an incision in the uterine wall, without entering the uterine cavity and
      without suturing the anterior and posterior walls of the uterus together, so
      minimising the trauma to the uterus. This new uterine compression suture is an
      effective and safe surgical treatment for PPH caused by atony. It has the
      potential to apply to intractable PPH after vaginal delivery.

PMID- 21176089
TI  - Changes in fetal death during 40 years-different trends for different gestational
      ages: a population-based study in Norway.
AB  - OBJECTIVE: To study changes in gestational-age-specific fetal death risks during
      a 40-year period. DESIGN: Register-based observational study. SETTING: The
      Medical Birth Registry of Norway. POPULATION: All pregnancies after 16 weeks of
      gestation in Norway from 1967 to 2006 (n = 2, 182, 756). METHOD: Changes in fetal
      death risk since 1967-1971 (reference) were estimated as absolute risks (rates)
      and relative risks (RR) in ongoing pregnancies at the following gestational
      weeks; 16-22, 23-29, 30-36 and 37-43. MAIN OUTCOME MEASURES: Fetal death.
      RESULTS: In all pregnancies lasting longer than 22 weeks, the fetal death rate
      decreased during 1967-2006. The greatest decline was in term pregnancies (37-43
      weeks) from 10.8 to 3.3 fetal deaths per 1000 at risk (crude RR 0.35; 95% CI 0.31
      0.38) comparing 1967-1971 with 2002-2006. In pregnancies at 30-36 weeks the fetal
      death rate declined from 4.5 to 1.1 per 1000 (crude RR 0.23; 95% CI 0.21-0.26).
      At 23-29 weeks, the rate declined from 2.8 to 1.3 per 1000 (crude RR 0.46; 95% CI
      0.40-0.52). An opposite trend was observed at early gestation (16-22 weeks) with
      an increase from 1.7 to 3.4 fetal deaths per 1000 ongoing pregnancies (crude RR
      2.05; 95% CI 1.84-2.27). Adjustments for maternal age, parity, multiple
      pregnancies, paternal age and pre-eclampsia did not significantly alter the
      estimated associations. CONCLUSION: Since 1967 the risk of fetal death has been
      reduced by almost 70% in pregnancies lasting longer than 22 weeks; however, at 16
      22 weeks of gestation there was an increase in risk. The causes of this increase
      should be further explored because it may be attributed to an increase in early
      delivery caused by the increased proportion of women being treated with cervical
      cone excision before pregnancy.

PMID- 21176090
TI  - Hot topics in aging research: protein translation and TOR signaling, 2010.
AB  - In this, the fourth installment of our annual Hot Topics review on mRNA
      translation and aging, we have decided to expand our scope to include recent
      findings related to the role of TOR signaling in aging. As new data emerge, it is
      clear that TOR signaling acts upstream of mRNA translation, as well as a variety
      of other cellular processes, to modulate longevity and healthspan in
      evolutionarily diverse species. This Hot Topics review will cover important new
      findings in this area that have occurred over the past year. These include the
      demonstration that the TOR substrate ribosomal S6 kinase modulates longevity in
      mammals, the potential for TOR inhibitors as therapeutic treatments for
      Alzheimer's disease, and further studies emphasizing the importance of
      differential translation of specific mRNAs for healthy aging and enhanced
      longevity.

PMID- 21176091
TI  - Age-associated increase in heterochromatic marks in murine and primate tissues.
AB  - Chromatin is highly dynamic and subject to extensive remodeling under many
      physiologic conditions. Changes in chromatin that occur during the aging process
      are poorly documented and understood in higher organisms, such as mammals. We
      developed an immunofluorescence assay to quantitatively detect, at the single
      cell level, changes in the nuclear content of chromatin-associated proteins. We
      found increased levels of the heterochromatin-associated proteins histone macro
      H2A (mH2A) and heterochromatin protein 1 beta (HP1beta) in human fibroblasts
      during replicative senescence in culture, and for the first time, an age
      associated increase in these heterochromatin marks in several tissues of mice and
      primates. Mouse lung was characterized by monophasic mH2A expression histograms
      at both ages, and an increase in mean staining intensity at old age. In the mouse
      liver, we observed increased age-associated localization of mH2A to regions of
      pericentromeric heterochromatin. In the skeletal muscle, we found two populations
      of cells with either low or high mH2A levels. This pattern of expression was
      similar in mouse and baboon, and showed a clear increase in the proportion of
      nuclei with high mH2A levels in older animals. The frequencies of cells
      displaying evidence of increased heterochromatinization are too high to be
      readily accounted for by replicative or oncogene-induced cellular senescence, and
      are prominently found in terminally differentiated, postmitotic tissues that are
      not conventionally thought to be susceptible to senescence. Our findings
      distinguish specific chromatin states in individual cells of mammalian tissues,
      and provide a foundation to investigate further the progressive epigenetic
      changes that occur during aging.

PMID- 21176093
TI  - Hypoxia and hypoxia-inducible factor 1alpha: potential links between angiogenesis
      and fibrogenesis in hepatic stellate cells.

PMID- 21176092
TI  - A nutrient-sensitive interaction between Sirt1 and HNF-1alpha regulates Crp
      expression.
AB  - Silent information regulator 2 (Sir2) orthologs are an evolutionarily conserved
      family of NAD-dependent protein deacetylases that regulate aging and longevity in
      model organisms. The mammalian Sir2 ortholog Sirt1 regulates metabolic and stress
      responses through the deacetylation of many transcriptional regulatory factors.
      To elucidate the mechanism by which Sirt1 controls gene expression in response to
      nutrient availability, we devised a bioinformatic screen combining gene
      expression analysis with phylogenetic footprinting to identify transcription
      factors as new candidate partners of Sirt1. One candidate target was HNF-1alpha,
      a homeodomain transcription factor that regulates pancreatic beta-cell and
      hepatocyte functions and is commonly mutated in patients with maturity-onset
      diabetes of the young (MODY). Interestingly, Sirt1 physically interacts with HNF
      1alphain vitro but does so in vivo only in nutrient-restricting conditions. This
      interaction requires 12-24 h of nutrient restriction and is dependent on protein
      synthesis. Both nutrient restriction and Sirt1 suppress HNF-1alpha
      transcriptional activity and the expression of one of its target genes, C
      reactive protein (Crp), in mouse primary hepatocytes. Pharmacological inhibition
      of Sirt1 blocks the suppression of Crp by nutrient restriction. Similarly, Crp
      expression is also suppressed in fasted and diet-restricted liver. Furthermore,
      Sirt1 and HNF-1alpha co-localize on two HNF-1alpha binding sites on the Crp
      promoter, leading to decreased acetylation of lysine 16 of histone H4 at these
      sites only in response to nutrient restriction. These findings reveal a novel
      nutrient-dependent interaction between Sirt1 and HNF-1alpha and provide important
      insight into the molecular mechanism by which Sirt1 mediates the anti-aging
      effects of diet restriction.

PMID- 21176095
TI  - Zirconia in fixed implant prosthodontics.
AB  - BACKGROUND: CAD/CAM technology in combination with zirconia ceramic has
      increasingly gained popularity in implant dentistry. PURPOSE: This narrative
      review presents the current knowledge on zirconia utilized as framework material
      for implant-borne restorations and implant abutments, laboratory tests and
      developments, clinical performance, and possible future trends for implant
      dentistry are addressed. MATERIAL AND METHODS: A review of available literature
      from 1990 through 2010 was conducted with search terms
      zirconia,""implants,""abutment,""crown," and "fixed dental prosthesis" using
      electronic databases (PubMed) and manual searching. RESULTS: Latest applications
      of zirconia in implant dentistry include implant abutments, multiple unit and
      full-arch frameworks as well as custom-made bars to support fixed and removable
      prostheses. High biocompatibility, low bacterial surface adhesion as well as
      favorable chemical properties of zirconia ceramics are reported. Zirconia
      stabilized with yttrium oxide exhibits high flexural strength and fracture
      toughness due to a transformation toughening mechanism. Preliminary clinical data
      confirmed the high stability of zirconia for abutments and as a framework
      material for implant borne crowns and fixed dental prostheses. Zirconia abutment
      or framework damage has rarely been encountered. However, veneering porcelain
      fractures are the most common technical complication in implant-supported
      zirconia restorations. These porcelain veneer failures have led to concerns
      regarding differences in coefficient of thermal expansions between core and
      veneering porcelain and their respective processing techniques. CONCLUSION: As
      presently evidence of clinical long-term data is missing, caution with regard to
      especially extensive implant-borne zirconia frameworks is recommended.

PMID- 21176096
TI  - Implant placement in combination with sinus membrane elevation without
      biomaterials: a 1-year study on 15 patients.
AB  - BACKGROUND: Membrane elevation in combination with implant placement without
      biomaterials is a rather new technique proposed for sinus lifting. PURPOSE: This
      study assessed the clinical outcome of such technique during the first year of
      loading. MATERIAL AND METHODS: Fifteen patients with a mean residual bone height
      of 6.2 mm were consecutively recruited for sinus lifting. After opening a
      replaceable bone window, the membrane was dissected from the sinus walls. A total
      of 28 implants were placed in the residual crest and they kept the membrane
      lifted upwards. After window repositioning, the flap was sutured. A 6-month
      healing period was allowed. Patients were re-examined after 12 months of loading.
      RESULTS: All the implants survived at the end of the follow-up. The 5.5 mm mean
      bone reformation was significantly lower than the 8.2 mm mean membrane lift
      achieved after implant placement. Regeneration at the distal surface of the most
      posterior implants was significantly less than at other aspects. The height of
      membrane lift was not correlated with the amount of regenerated bone.
      CONCLUSIONS: All of the 28 implants placed in combination with sinus membrane
      elevation were stable during the first year of loading. No extra costs for
      biomaterial or morbidity for bone harvesting were necessary.

PMID- 21176097
TI  - Soft tissue augmentation in connection to dental implant treatment using a
      synthetic, porous material--a case series with a 6-month follow-up.
AB  - BACKGROUND: Bony defects/concavities in the aesthetic zone of maxillae may
      interfere with the results of prosthetic procedures by producing shading superior
      to the crown. Such regions can be augmented either by bone or soft tissue
      autografts, allografts, or xenografts. Tissue shrinkage is thus anticipated, and
      a method to objectively measure the tissue change is valuable. PURPOSE: The aim
      of this study was to evaluate the use of a synthetic, porous material made of
      polyurethaneurea for buccal soft tissue augmentation in connection with implant
      placement in the maxillary front region. Further, to measure over time the change
      in buccal contour using a computerized technique. MATERIALS AND METHODS: Ten
      patients received 12 Artelon(r) cylinders (5 * 10 mm) in connection to implant
      placement. Preoperative and postoperative (at 3 and 6 months) study casts were
      obtained for computer measurements, using the preoperative reference model as a
      base. The volume created between the surfaces of the reference model and each of
      the two following superimposed models was measured in cubic millimeter.
      Differences in volume from pretreatment to 3 and 6 months, respectively, were
      compared. RESULTS: The clinical observation during follow-up showed normal
      healing. The increase in mean buccal tissue volume was 50 mm(3) (SD 18) after 3
      months and 43 mm(3) (SD 21) after 6 months, measured over a 6 mm * 8 mm area in
      the maxillary front region, in comparison to before insertion of the cylinder.
      The reduction from 3 to 6 months was not statistically significant (p = .17).
      CONCLUSION: A synthetic, porous material for soft tissue augmentation was tested
      in connection to implant placement in the aesthetic zone of maxillae. The buccal
      contour was followed-up for 6 months using a computer volumetric technique on
      preoperative and postoperative study casts. Measured tissue volume showed an
      obvious increase during the study period. The material was biologically well
      received.

PMID- 21176098
TI  - Tomographic, histological, and immunohistochemical evidences on the use of N
      butyl-2-cyanoacrilate for onlay graft fixation in rabbits.
AB  - BACKGROUND: The bone tissue responses to Cyanoacrylate have been described in the
      literature, but none used N-butyl-2-cyanoacrilate (NB-Cn) for bone graft
      fixation. PURPOSE: The aims of the study were: (a) to analyze the bone grafts
      volume maintenance fixed either with NB-Cn or titanium screw; (b) to assess the
      incorporation of onlay grafts on perforated recipient bed; and (c) the
      differences of expression level of tartrate-resistant acid phosphatase (TRAP)
      protein involved in bone resorption. MATERIALS AND METHODS: Eighteen New Zealand
      White rabbits were submitted to calvaria onlay grafting on both sides of the
      mandible. On one side, the graft was fixed with NB-Cn, while on the other hand
      the bone graft was secured with an osteosynthesis screw. The computed tomography
      (CT) was performed just after surgery and at animals sacrifice, after 1 (n = 9)
      and 6 weeks (n = 9), in order to estimate the bone grafts volume along the
      experiments. Histological sections of the grafted areas were prepared to evaluate
      the healing of bone grafts and to assess the expression of TRAP protein. RESULTS:
      The CT scan showed better volume maintenance of bone grafts fixed with NB-Cn (p
      <= 0.05) compared with those fixed with screws, in both experimental times
      (analysis of variance). The immunohistochemical evaluation showed that the TRAP
      expression in a 6-week period was significantly higher compared with the 1-week
      period, without showing significant difference between the groups (Wilcoxon and
      Mann-Whitney). Histological analysis revealed that the NB-Cn caused periosteum
      damage, but provided bone graft stabilization and incorporation similar to the
      control group. CONCLUSION: The perforation provided by screw insertion into the
      graft during fixation may have triggered early revascularization and remodeling
      to render increased volume loss compared with the experimental group. These
      results indicate that the NB-Cn possesses equivalent properties to titanium screw
      to be used as bone fixation material in osteosynthesis.

PMID- 21176099
TI  - Fracture strength and failure mode of maxillary implant-supported provisional
      single crowns: a comparison of composite resin crowns fabricated directly over
      PEEK abutments and solid titanium abutments.
AB  - BACKGROUND: Polyetheretherketone (PEEK) temporary abutments have been recently
      introduced for making implant-supported provisional single crowns. Little
      information is available in the dental literature on the durability of
      provisional implant-supported restorations. PURPOSE: The objectives of this study
      were to evaluate the fracture strength of implant-supported composite resin
      crowns on PEEK and solid titanium temporary abutments, and to analyze the failure
      types. MATERIAL AND METHODS: Three types of provisional abutments, RN synOcta
      Temporary Meso Abutment (PEEK; Straumann), RN synOcta Titanium Post for Temporary
      Restorations (Straumann), and Temporary Abutment Engaging NobRplRP (Nobel
      Biocare) were used, and provisional screw-retained crowns using composite resin
      (Solidex) were fabricated for four different locations in the maxilla. The
      specimens were tested in a universal testing machine at a crosshead speed of 1
      mm/minute until fracture occurred. The failure types were analyzed and further
      categorized as irreparable (Type 1) or reparable (Type 2). RESULTS: No
      significant difference was found between different abutment types. Only for the
      position of the maxillary central incisor, composite resin crowns on PEEK
      temporary abutments showed significantly lower (p < 0.05) fracture strength (95
      +/- 21 N) than those on titanium temporary abutments (1,009 +/- 94 N). The most
      frequently experienced failure types were cohesive fractures of the composite
      resin crowns (75 out of 104), followed by screw loosening (18 out of 104).
      According to reparability, the majority of the specimens were classified as Type
      1 (82 out of 104). Type 2 failures were not often observed (22 out of 104).
      CONCLUSIONS: Provisional crowns on PEEK abutments showed similar fracture
      strength as titanium temporary abutments except for central incisors. Maxillary
      right central incisor composite resin crowns on PEEK temporary abutments
      fractured below the mean anterior masticatory loading forces reported to be
      approximately 206 N.

PMID- 21176100
TI  - Comparison of fit accuracy between Procera(r) custom abutments and three implant
      systems.
AB  - BACKGROUND: Although increase of misfit has been reported when associating
      implant and abutment from different manufacturers, Procera custom abutment has
      been universally used in clinical practice. PURPOSE: The purpose of this
      investigation was to compare the vertical gap of zirconia Procera(r) abutment
      associated with implants from the same manufacturer (Procera manufacturer) and
      two other implant systems. MATERIALS AND METHODS: Twenty-four zirconia Procera
      abutments were produced using computer-assisted design and manufacture and paired
      with (a) eight MK III, RP 4.1 * 10 mm implants (Nobel BiocareTM, Goteborg,
      Sweden) - GNB group (Nobel Biocare group); (b) eight Try on, 4.1 * 10 mm implants
      (Sistema de Implantes, Sao Paulo, Brazil) - ES group (SIN experimental group) ;
      and (c) eight Master screw, 4.1 * 10 mm implants (Conexao(r) Sistema de Protese,
      Sao Paulo, Brazil) - EC group (Conexao experimental group). A comparison of the
      vertical misfit at the implant-abutment interface was taken at six measuring
      sites on each sample using scanning electron microscopy with a magnification of
      408*. One-way analysis of variance was used to test for differences, and Tukey's
      test was used for pair-wise comparison of groups (alpha = 0.05). RESULTS:
      Significant differences relative to average misfit were found when Procera
      abutments were associated with other implant manufacturers. The ES group and EC
      group did not differ significantly, but both demonstrated significantly larger
      average misfit than the GNB group (p = .001). The average misfit was 5.7 um +/-
      0.39, 9.53 um +/- 0.52, and 10.62 um +/- 2.16, respectively, for groups GNB, ES,
      and EC. CONCLUSION: The association of Procera zirconia abutment with other
      implant systems different from its manufacturer demonstrated significant
      alteration of vertical misfit at implant-abutment interface.

PMID- 21176102
TI  - Future directions of stroke prevention in atrial fibrillation: the potential
      impact of novel anticoagulants and stroke risk stratification.
AB  - Stroke prevention in atrial fibrillation is of paramount importance given its
      associated morbidity and mortality. The many challenges of warfarin limit its
      effective use in real-world clinical practice. We are entering an exciting
      therapeutic era as new classes of anticoagulants, including direct thrombin
      inhibitors, factor Xa inhibitors and novel vitamin K antagonists, are being
      evaluated for possible use in this patient population. If proven to be as
      efficacious as warfarin and safer, expanded use of these novel agents to lower
      risk subgroups may be justified. It is imperative that providers be aware of the
      many advantages and potential challenges posed by use of these novel agents in
      routine clinical care. An understanding of individual pharmacokinetic profiles
      and potential drug-drug and drug-disease interactions will translate into
      improved effectiveness in real-world practice.

PMID- 21176103
TI  - Large-scale production, purification and bioactivity assay of recombinant human
      interleukin-6 in the methylotrophic yeast Pichia pastoris.
AB  - A DNA fragment containing the mature human interleukin (IL)-6 sequence was cloned
      into pPICZalphaA, generating a fusion protein with the alpha factor from baker's
      yeast and integrated into the genome of Pichia pastoris strain X-33. Recombinant
      yeast transformants with high-level rhIL-6 production were identified, secreting
      as much as 280 mg L(-1) rhIL-6 after 4 days of induction by methanol. The rhIL-6
      was purified by PEG-8000 precipitation, followed by DEAE anion exchange and
      Sephadex G-75 gel filtration, yielding over 95% pure rhIL-6 at about 170 mg L(-1)
      . Mass spectrometry analysis showed that the rhIL-6 has a molecular weight of
      20,908.85 Da, which is close to the mass calculated from the sequence of the
      protein. Functional analysis of the purified rhIL-6 using the lymphocyte
      proliferation assay by an MTT [3-(4,5-dimethylthiazolyl-2)-2,5-diphenyl
      tetrazoliumbromide] method demonstrated a specific activity that is at least
      fivefold higher than the commercial rhIL-6 produced in Escherichia coli. In
      summary, the experimental procedure we have reported here allows us to obtain a
      large amount of rhIL-6 from P. pastoris suitable for subsequent biophysical
      studies.

PMID- 21176104
TI  - Association of CHRM2 polymorphisms with severity of alcohol dependence.
AB  - The cholinergic muscarinic 2 receptor (CHRM2) gene has been considered a
      candidate gene for the alcohol dependence in that it might underpin certain risk
      factors for this condition. This study examined variations in the CHRM2 between
      the patients with alcohol dependence and population controls in Korean and
      explored the associations between CHRM2 polymorphisms and severity of symptoms in
      the patients with alcohol dependence. One hundred and fifty-five patients with
      alcohol dependence, defined by the Alcohol Use Disorders Identification Test
      (AUDIT) and the Alcohol Dependence Scale (ADS) to measure the severity of
      symptoms, and one hundred and ninety-five population controls were drawn in the
      study. Three single nucleotide polymorphisms (SNPs) of CHRM2 were genotyped using
      the TaqMan assay and analyzed with the severity of symptoms of alcohol
      dependence. We found that although SNP rs324650 showed marginal association with
      the risk of alcohol dependence (P = 0.03), the significance of the result was not
      sustained after multiple corrections. SNP rs1824024 was significantly associated
      with the AUDIT and ADS scores in patients (P = 0.005 and 0.003, respectively).
      These findings suggested that the muscarinic acetylcholine function might be
      related not with alcohol dependence itself but with the severity of alcohol
      dependence in Korean population.

PMID- 21176105
TI  - Skin manifestations in autoinflammatory syndromes.
AB  - Autoinflammatory diseases encompass a group of inflammatory diseases that are non
      infectious, non-allergic, non-autoimmune and non-immunodeficient. The term was
      initially coined for a small group of familial periodic fever syndromes of which
      familial Mediterranean fever (FMF) is the most common and best known. Genetic and
      molecular analyses demonstrated for the majority of these diseases an impairment
      of inflammasomes to cause an increased activity of an interleukin-1-dependent
      inflammatory response. Over the last years an increasing number of either rare
      hereditary syndromes or acquired common diseases could be summarized under the
      designation of autoinflammatory disease, thus creating an emerging new rubric of
      inflammatory diseases. Many of them display cutaneous manifestations as both
      concomitant or more rarely main symptoms. To name some of them like erysipelas
      like erythema in FMF; urticaria-like rashes in tumor necrosis factor receptor 1-
      or cryopyrin-associated periodic syndromes (TRAPS, CAPS), hyperimmunoglobulin D
      syndrome (HIDS) or Schnitzler syndrome; pyoderma gangrenosum and acne in PAPA
      syndrome; or behcetoid aphthous ulcerations in HIDS and PFAPA syndrome. Based on
      the new insights into pathogenesis one increasingly realizes the good response of
      these diseases to IL-1 antagonist therapies.

PMID- 21176106
TI  - Detailed exposure assessment of dietary furan for infants consuming commercially
      jarred complementary food based on data from the DONALD study.
AB  - Furan is a possible human carcinogen regularly occurring in commercially jarred
      complementary foods. This paper will provide a detailed exposure assessment for
      babies consuming these foods considering different intake scenarios. The
      occurrence data on furan in complementary foods were based on our own headspace
      gas chromatography/mass spectrometry (HS-GC/MS) analytical results (n = 286). The
      average furan content in meals and menus was between 20 and 30 ug kg(-1), which
      is in excellent agreement with results from other European countries. Using
      measured food consumption data from the Dortmund Nutritional and Anthropometric
      Longitudinally Designed (DONALD) study, the average exposures for consumers of
      commercially jarred foods ranged between 182 and 688 ng kg(-1) bw day(-1), with a
      worst case scenario for P95 consumers ranging between 351 and 1066 ng kg(-1) bw
      day(-1). The exposure data were then used to characterize risk using the margin
      of exposure method based on a benchmark dose lower confidence limit for a 10%
      response (BMDL10) of 1.28 mg kg(-1) bw day(-1) for hepatocellular tumours in
      rats. The margin of exposures (MOEs) were below the threshold of 10 000, which is
      often used to define public health risks, in all scenarios, ranging between 7022
      and 1861 for average consumers and between 3642 and 1200 for the P95 consumers.
      Mitigative measures to avoid furan in complementary foods should be of high
      priority for risk management.

PMID- 21176107
TI  - Use of negative pressure wound therapy in the management of infected abdominal
      wounds containing mesh: an analysis of outcomes.
AB  - The purpose of this study was to examine the clinical outcomes of negative
      pressure wound therapy (NPWT) using reticulated open-cell foam (ROCF) in the
      adjunctive management of abdominal wounds with exposed and known infected
      synthetic mesh. A non randomised, retrospective review of medical records for 21
      consecutive patients with infected abdominal wounds treated with NPWT was
      conducted. All abdominal wounds contained exposed synthetic mesh [composite,
      polypropylene (PP), or knitted polyglactin 910 (PG) mesh]. Demographic and
      bacteriological data, wound history, pre-NPWT and comparative post-NPWT,
      operative procedures and complications, hospital length of stay (LOS) and wound
      healing outcomes were all analysed. Primary endpoints measured were (1) hospital
      LOS prior to initiation of NPWT, (2) total time on NPWT, (3) hospital LOS from
      NPWT initiation to discharge and (4) wound closure status at discharge. A total
      of 21 patients with abdominal wounds with exposed, infected mesh were treated
      with NPWT. Aetiology of the wounds was ventral hernia repair (n = 11) and acute
      abdominal wall defect (n = 10). Prior to NPWT initiation, the mean hospital LOS
      for the composite, PP and PG meshes were 76 days (range: 21-171 days), 51 days
      (range: 32-62 days) and 19 days (range: 12-39 days), respectively. The mean
      hospital LOS following initiation of NPWT for wounds with exposed composite, PP
      and PG mesh were 28, 31 and 32 days, respectively. Eighteen of the 21 wounds
      (86%) reached full closure after a mean time of 26 days of NPWT and a mean
      hospital LOS of 30 days postinitiation of NPWT. Three wounds, all with composite
      mesh left in situ, did not reach full closure, although all exhibited decreased
      wound dimensions, granulating beds and decreased surface area exposure of mesh.
      During NPWT/ROCF, one hypoalbuminemic patient with exposed PP mesh developed an
      enterocutaneous fistula over a prior enterotomy site. This patient subsequently
      underwent total mesh extraction, takedown of the fistula and PP mesh replacement
      followed by reinstitution of NPWT and flap closure. In addition to appropriate
      systemic antibiotics and nutritional optimisation, the adjunctive use of NPWT
      resulted in successful closure of 86% of infected abdominal wounds with exposed
      prosthetic mesh. Patient hospital LOS (except those with PG mesh), operative
      procedures and readmissions were decreased during NPWT compared with treatment
      prior to NPWT. Future multi-site prospective, controlled studies would provide a
      strong evidence base from which treatment decisions could be made in the
      management of these challenging and costly cases.

PMID- 21176108
TI  - Amisulpride-induced seizurogenic effect: a potential role of opioid receptor
      linked transduction systems.
AB  - This study was designed to investigate the role of opioid receptors, gamma
      aminobutyric acid (GABA) receptors, mast cells and histamine receptors (H(1)
      subtype) in the seizurogenic effect of amisulpride on mice. A single injection of
      amisulpride (180 mg/kg) was employed to evaluate the seizurogenicity of the drug
      in mice. Seizures were assessed in terms of a composite seizure severity score
      (SSS), time of the onset of straub-like tail, onset of jerky movements of whole
      body, convulsions and death. Amisulpride administration (180 mg/kg) induced a
      significant pro-convulsant effect in mice as measured in terms of the SSS (21.12
      +/- 2.71) and a significant decrease in the time latency of the onset of straub
      like tail (132.45 +/- 12.31), jerky movements of whole body (153.28 +/- 14.12),
      convulsions (184.97 +/- 13.11) and death (100%). Moreover, prior administration
      of naloxone, cetrizine, sodium cromoglycate and gabapentin, respectively,
      attenuated this seizurogenic activity that amisulpride exerted on mice (p <
      0.05). Therefore, it may be suggested that amisulpride exerts a seizurogenic
      effect on mice possibly via an opioid receptor activation-dependent release of
      histamine from the mast cells and a simultaneous inhibition of GABA release.

PMID- 21176109
TI  - Doxycycline dose-dependently inhibits MMP-2-mediated vascular changes in 2K1C
      hypertension.
AB  - Hypertension induces vascular alterations that are associated with up-regulation
      of matrix metalloproteinases (MMPs). While these alterations may be blunted by
      doxycycline, a non-selective MMPs inhibitor, no previous study has examined the
      effects of different doses of doxycycline on these alterations. This is important
      because doxycycline has been used at sub-antimicrobial doses, and the use of
      lower doses may prevent the emergence of antibiotic-resistant microorganisms. We
      studied the effects of doxycycline at 3, 10 and 30 mg/kg per day on the vascular
      alterations found in the rat two kidney-one clip (2K1C) hypertension (n = 20
      rats/group). Systolic blood pressure (SBP) was monitored during 4 weeks of
      treatment. We assessed endothelium-dependent and independent relaxations.
      Quantitative morphometry of structural changes in the aortic wall was studied,
      and aortic MMP-2 levels/proteolytic activity were determined by gelatin and in
      situ zymography, respectively. All treatments attenuated the increases in SBP in
      hypertensive rats (195.4 +/- 3.9 versus 177.2 +/- 6.2, 176.3 +/- 4.5, and 173 +/-
      5.1 mmHg in 2K1C hypertensive rats treated with vehicle, or doxycycline at 3, 10,
      30 mg/kg per day, respectively (all p < 0.01). However, only the highest dose
      prevented 2K1C-induced reduction in endothelium-dependent vasorelaxation (p <
      0.05), vascular hypertrophy and increases in MMP-2 levels (all p < 0.05). In
      conclusion, our results suggest that relatively lower doses of doxycycline do not
      attenuate the vascular alterations found in the 2K1C hypertension model, and only
      the highest dose of doxycycline affects MMPs and vascular structure. Our results
      support the idea that the effects of doxycycline on MMP-2 and vascular structure
      are pressure independent.

PMID- 21176110
TI  - Associations between physical and mental health problems and sexual dysfunctions
      in sexually active Danes.
AB  - INTRODUCTION: Studies have shown a high prevalence of sexual dysfunctions among
      individuals with a variety of health problems. AIM: To obtain a population-based
      assessment of these matters, we studied associations between indicators of
      physical and mental health problems and sexual dysfunctions in Denmark. METHODS:
      We used questionnaire data from 4,415 sexually active men (mean age 48 years) and
      women (mean age 45 years) who participated in a nationally representative survey
      in 2005. Cross-sectional associations of overall health and physical and mental
      health problems with sexual dysfunctions in the last year were estimated by
      logistic regression-derived, confounder-adjusted odds ratios (OR(adj) ). MAIN
      OUTCOME MEASURES: We calculated OR(adj) with 95% confidence intervals (CI) for
      erectile dysfunction, anorgasmia, premature ejaculation, and dyspareunia in men,
      for lubrication insufficiency, anorgasmia, dyspareunia, and vaginismus in women,
      and for sexual dysfunction and sexual difficulties overall in both sexes.
      RESULTS: Sexual dysfunction was significantly more common among participants with
      poor self-rated health (OR(adj) 1.86, 95% CI 1.05-3.33 in men, OR(adj) 1.91, 1.08
      3.37 in women). Physical health problems were significantly associated with male
      sexual dysfunctions (OR(adj) 1.75, 1.18-2.61), whereas mental health problems
      were significantly associated with female sexual dysfunctions (OR(adj) 2.59, 1.60
      4.22). CONCLUSION: Among sexually active Danes, poor self-reported overall health
      is associated with increased rates of sexual dysfunction in both sexes, with
      physical health problems mainly affecting men's sex lives, and mental health
      problems being strongly associated with female sexual dysfunction.

PMID- 21176111
TI  - Exposure to phosphodiesterase type 5 inhibitors stimulates aromatase expression
      in human adipocytes in vitro.
AB  - INTRODUCTION: Prolonged tadalafil administration in men with erectile dysfunction
      is associated with increased testosterone (T): estradiol (E(2)) ratio mainly
      related to reduction of E(2) levels. AIM: To investigate the presence of
      phosphodiesterase type 5 (PDE5) isoenzyme in primary human visceral adipocytes
      and whether different PDE5 inhibitors (PDE5i) could directly modulate aromatase
      (ARO) expression in differentiated human visceral adipocytes in culture. MAIN
      OUTCOME MEASURES: PDE5 mRNA and protein expression in primary human visceral
      adipocytes as well as mRNA and protein expression of ARO, with functional
      activity after selective PDE5 blockade by tadalafil and sildenafil. METHODS:
      Purified primary human visceral pre-adipocytes were differentiated ex vivo and
      were exposed to tadalafil or sildenafil (1 uM) for different intervals of time (6
      12-24-96 hours). ARO mRNA content and expression were measured by Western Blot
      and quantitative reverse transcription-polymerase chain reaction (qRT-PCR),
      respectively. T and E(2) in supernatants were measured by ELISA also in the
      presence of letrozole. RESULTS: Differentiated adipocytes were found to express
      detectable levels of PDE5 transcripts. Acute exposure (6 hours) to both PDE5i
      tadalafil and sildenafil increased ARO mRNA expression by 4.7- and 2.8-fold,
      respectively (P < 0.001). ARO mRNA and protein levels were increased by the
      treatment with PDE5i in a time- and dose-dependent manner. Such effect was
      mimicked by 8-bromo-cGMP but was lost after 24 and 96 hours; differently, the
      PDE3B specific inhibitor milrinone (1 uM), displayed no effect. Accordingly, long
      term exposure (24 and 96 hours) to PDE5i caused a significant increase in E(2)
      concentrations in the supernatant (1.7 and 2 fold, respectively; P < 0.001), with
      a parallel reduction of T (15% and 30%, respectively; P < 0.001). Such effect was
      reversed by the co-incubation with the specific ARO-inhibitor letrozole.
      CONCLUSIONS: Our results demonstrate that PDE5 is expressed in human visceral
      adipocytes and that acute exposure to PDE5i selectively stimulates ARO
      expression, which is related to a specific PDE5 blockade. We speculate that
      modulation of ARO activity by PDE5i could be one of the mechanisms responsible,
      at least in part, for the beneficial effects of PDE5i on endothelial and
      metabolic functions.

PMID- 21176112
TI  - The relationship between sexual functioning and depressive symptomatology in
      postpartum women: a pilot study.
AB  - INTRODUCTION: Previous research on postpartum sexuality has primarily focused on
      the impact of physical factors on the resumption and frequency of sexual
      intercourse; fewer studies have focused on the impact of psychological factors on
      women's sexual functioning. AIM: The aim of this study is to assess current
      sexual functioning and sexual behavior in women with and without symptoms of
      postpartum depression using validated measures of postpartum depression and
      sexual functioning. METHODS: Women attending postpartum appointments were
      consecutively recruited over a 12-month period and completed questionnaires
      assessing sexual functioning, current sexual behavior, and mental health. MAIN
      OUTCOME MEASURES: The Female Sexual Function Index (FSFI), the Edinburgh
      Postnatal Depression Scale (EPDS), and items assessing current sexual behaviors.
      RESULTS: A total of 77 women returned completed questionnaire packages (mean
      postpartum weeks: 13, range 3-24). Of these, 57 women (74%) had engaged in sexual
      activity with a partner in the 4 weeks prior to completing the questionnaire. The
      mean FSFI score was 23.0 (range 6-34), with 37 women (65%) scoring in the range
      associated with clinical sexual dysfunction. Women with elevated EPDS scores had
      significantly lower total FSFI, arousal, orgasm, and satisfaction FSFI subscale
      scores (all P values <0.005) than nondepressed women, suggesting more problematic
      sexual functioning. Desire, lubrication, and pain FSFI subscale scores were not
      significantly associated with depression status. CONCLUSIONS: A substantial
      proportion of women experience sexual problems in the postpartum period; these
      problems are particularly pronounced among women with symptoms of postpartum
      depression. Longitudinal research is needed to better understand the relationship
      between sexual dysfunction and depression among postpartum women, and to identify
      implications for prevention and treatment of both conditions.

PMID- 21176113
TI  - Male infertility and depression: a neglected problem in the Middle East.
AB  - INTRODUCTION: Little attention has been paid to the psychological status of
      infertile men from developing countries who have been traditionally stigmatized
      as feeble and ineffective. AIM: The aim of this study is to evaluate the
      prevalence of depression and its socio-demographic correlates in a sample of
      Iranian infertile men. METHODS: One hundred and fourteen infertile men filled out
      the 21-item Beck Depression Inventory. Men who scored >= 17 were considered
      depressed and those with the score <= 16 were assumed to be nondepressed. MAIN
      OUTCOME MEASURES: (i) Comparison between depressed and non-depressed men
      regarding age, education level, economic status, ethnicity, age at time of
      marriage, duration, and type of infertility and regular cigarette smoking. (ii)
      Independent risk factors for depression. RESULTS: The mean age of participants
      was 34.1 +/- 7.1 years. The diagnosis of depression was made in 42.9% of
      infertile men. Current age, age at marriage, economic status, and type of
      infertility were not statistically different between two groups (P > 0.05).
      Statistically significant association was detected between depression symptoms
      and education (P < 0.001), cigarette smoking (P < 0.008), and duration of
      infertility (P < 0.03). In an adjusted multiple regression model, education (odds
      ratio [OR] 0.2; confidence interval [CI] 0.06-0.5, P < 0.003), ethnicity (OR 4.5;
      CI 1.5-13.3, P < 0.006), and cigarette smoking (OR 5.1; CI 1.4-18.5, P < 0.01)
      retained their significance, while duration of infertility lost its power.
      CONCLUSION: Depression among Iranian infertile men is remarkably higher in
      comparison with Western countries. Azaris, cigarette smokers, and individuals
      with low educational level are at higher risk of developing depression among
      infertile men.

PMID- 21176114
TI  - Biopsychosocial determinants of men's sexual desire: testing an integrative
      model.
AB  - INTRODUCTION: There is a severe lack of studies on male sexual desire and its
      biopsychosocial determinants. Most of the studies are focused on female sexual
      interest and are based on the contribution of single dimensions instead of the
      interaction between them. AIM: The aim of the present study was to test a
      conceptual model considering the interrelated role of biopsychosocial factors on
      male sexual desire. This model allowed us to test not only the unique impact of
      predictors that are traditionally related to sexual desire, but also how their
      interaction affects sexual desire in men. METHODS: Two hundred and thirty seven
      men from the general population were assessed according to age (mean age = 35,
      standard deviation = 11), medical problems, psychopathology, dyadic adjustment,
      and cognitive-emotional factors. MAIN OUTCOME MEASURES: Psychopathology measured
      by the Brief Symptom Inventory, dysfunctional sexual beliefs measured by the
      Sexual Dysfunctional Beliefs Questionnaire, thoughts and emotions in sexual
      context measured by the Sexual Modes Questionnaire, dyadic adjustment measured by
      the Dyadic Adjustment Scale, medical condition measured by the Medical History
      Formulation, and sexual desire measured by the Sexual Desire subscale of the
      International Index of Erectile Function. RESULTS: Results showed that cognitive
      factors (sexual beliefs and automatic thoughts during sexual activity) were the
      best predictors of sexual desire in men. Specifically, beliefs related to
      restrictive attitudes toward sexuality, erection concerns, and lack of erotic
      thoughts in sexual context, had a significant direct effect on reduced sexual
      desire. Moreover, this set of cognitive-emotional factors also mediated the
      relationship between medical problems, age, and sexual desire. CONCLUSION:
      Results from this integrative approach highlighted the role of cognitive factors
      related to cultural values (dysfunctional sexual beliefs) and distraction
      mechanisms during sexual context (automatic thoughts) in male sexual interest.
      Findings support the need to include cognitive dimensions in the assessment and
      treatment of sexual desire problems, considering their involvement as
      vulnerability or resiliency factors for deficient sexual desire in men. Moreover,
      these factors surpassed the importance of the remaining factors (particularly, of
      medical factors and psychopathology), showing that, despite the lack of studies,
      male sexuality is better conceptualized from a biopsychosocial perspective.

PMID- 21176115
TI  - Adverse side effects of 5alpha-reductase inhibitors therapy: persistent
      diminished libido and erectile dysfunction and depression in a subset of
      patients.
AB  - INTRODUCTION: 5alpha-reductase inhibitors (5alpha-RIs), finasteride and
      dutasteride, have been approved for treatment of lower urinary tract symptoms,
      due to benign prostatic hyperplasia, with marked clinical efficacy. Finasteride
      is also approved for treatment of hair loss (androgenetic alopecia). Although the
      adverse side effects of these agents are thought to be minimal, the magnitude of
      adverse effects on sexual function, gynecomastia, depression, and quality of life
      remains ill-defined. AIM: The goal of this review is to discuss 5alpha-RIs
      therapy, the potential persistent side effects, and the possible mechanisms
      responsible for these undesirable effects. METHODS: We examined data reported in
      various clinical studies from the available literature concerning the side
      effects of finasteride and dutasteride. MAIN OUTCOME MEASURES: Data reported in
      the literature were reviewed and discussed. Results.  Prolonged adverse effects
      on sexual function such as erectile dysfunction and diminished libido are
      reported by a subset of men, raising the possibility of a causal relationship.
      CONCLUSIONS: We suggest discussion with patients on the potential sexual side
      effects of 5alpha-RIs before commencing therapy. Alternative therapies may be
      considered in the discussion, especially when treating androgenetic alopecia.

PMID- 21176116
TI  - Glutathione S-transferase M1 (GSTM1) polymorphism is associated with atopic
      dermatitis susceptibility in a Korean population.
AB  - Atopic dermatitis (AD) is a chronic pruritic skin condition affecting as much as
      15% of children in industrialized countries. While the underlying pathophysiology
      of AD is not entirely understood, several studies have suggested that AD may
      mediated by oxidative stress. Glutathione S-transferases (GSTs) are a class of
      polymorphic enzymes that function to protect against oxidative stress. To
      identify any possible associations between GSTs polymorphisms and AD
      susceptibility, the prevalence of two specific polymorphisms -GSTM1 and GSTT1
      (homozygous deletion vs. undeleted) - were quantified by multiplex PCR in 145
      patients with AD and 267 healthy controls. In individuals with AD, GSTM1/GSTT1
      polymorphisms were compared with family history of AD, age of disease onset,
      disease severity [per SCORing Atopic Dermatitis (SCORAD)], serum IgE level and
      presence of other allergic diseases. While the GSTM1-null genotype was found to
      be significantly associated with AD (P = 0.033, OR = 1.579, 95% CI = 1.037
      2.403), the correlation between the GSTT1-null genotype and AD did not reach
      statistical significance (P = 0.577, OR = 1.125, 95% CI = 0.744-1.702). The GSTM1
      null genotype was also found to be significantly associated with a childhood
      onset of AD, the absence of other allergic diseases, and a family history of AD.
      In combination, these results suggest that GSTM1 is associated with AD
      susceptibility in Korean subjects.

PMID- 21176117
TI  - A proliferative melanoma cell phenotype is responsive to RAF/MEK inhibition
      independent of BRAF mutation status.
AB  - Oncogenic mutations within the MAPK pathway are frequent in melanoma, and
      targeting of MAPK signaling has yielded spectacular responses in a significant
      number of patients that last for several months before relapsing. We investigated
      the effects of two different inhibitors of MAPK signaling in proliferative and
      invasive melanoma cell cultures with various mutations in the MAPK pathway.
      Proliferative melanoma cells were more susceptible to pathway inhibition than
      invasive phenotype cells, irrespective of BRAF mutation status, while invasive
      phenotype cell response was dependent on BRAF mutation status. Critically, MAPK
      pathway inhibition of proliferative phenotype cells resulted in acquisition of
      invasive phenotype characteristics. These results show that melanoma cell
      phenotype is an important factor in MAPK pathway inhibition response. This
      suggests that while current therapeutic strategies target proliferative melanoma
      cells, future approaches should also account for the invasive phenotype
      population.

PMID- 21176118
TI  - Incidence of rhegmatogenous retinal detachments after intravitreal antivascular
      endothelial factor injections.
AB  - PURPOSE: To determine the incidence of rhegmatogenous retinal detachments (RD)
      after intravitreal injection in six high-volume centres. METHODS:   A
      consecutive, interventional, multicenter case series measured the incidence of RD
      in patients receiving intravitreal anti-VEGF. A total of 35 942 intravitreal anti
      VEGF injections (the number of the injections determined by review of injection
      log books over a 3 year period) were performed under sterile conditions with the
      patient in a supine position. Injections were given 3.5-4.0 mm behind the limbus
      in a tunnelled fashion. RESULTS: During 36 consecutive months, five RD were
      reported, between 2 and 6 days after the injection. Of the affected eyes, four
      were myopic -1.75 to -5.5 dpt. The incidence rate of rhegmatogenous RD was 0.013%
      (5/35 942) per injection. CONCLUSIONS: The incidence of RD in our community
      setting was very low (1 per 7188 injections). All RD occurred during the early
      postoperative period. The risks of RD can be minimized by a careful injection
      technique.

PMID- 21176119
TI  - From eggs to hearts: what is the link between cyclic ADP-ribose and ryanodine
      receptors?
AB  - It was first proposed that cyclic ADP-ribose (cADPR) could activate ryanodine
      receptors (RyR) in 1991. Following a subsequent report that cADPR could activate
      cardiac RyR (RyR2) reconstituted into artificial membranes and stimulate Ca(2+) 
      release from isolated cardiac SR, there has been a steadily mounting stockpile of
      publications proclaiming the physiological and pathophysiological importance of
      cADPR in the cardiovascular system. It was only 2 years earlier, in 1989, that
      cADPR was first identified as the active metabolite of nicotinamide adenine
      dinucleotide (NAD), responsible for triggering the release of Ca(2+)  from crude
      homogenates of sea urchin eggs. Twenty years later, can we boast of being any
      closer to unraveling the mechanisms by which cADPR modulates intracellular Ca(2+)
      -release? This review sets out to examine the mechanisms underlying the effects
      of cADPR and ask whether cADPR is an important signaling molecule in the heart.

PMID- 21176121
TI  - Report of the 60th annual meeting of the American Society of Human Genetics:
      several steps toward discoveries.
AB  - A report of the 60th annual meeting of the American Society of Human Genetics in
      Washington, DC, USA, 2-6 November 2010.

PMID- 21176120
TI  - Experimental infection of common warthogs (Phacochoerus africanus) and bushpigs
      (Potamochoerus larvatus) with classical swine fever virus II: A comparative
      histopathological study.
AB  - Wild African Suidae, the common warthog (Phacochoerus africanus) and bushpig
      (Potamochoerus larvatus), were experimentally infected with classical swine fever
      (CSF) virus following the diagnosis of CSF subtype 2.1 in domestic pigs in South
      Africa in 2005. No data regarding the susceptibility or potential lesions of
      these African wild suids are available. Seven subadult warthogs and six bushpigs
      were captured and infected intranasally with the South African isolate. Two in
      contact control animals of the same species in each experiment verified intra
      species transmission. Surviving animals were euthanized after 44 days. Formalin
      fixed tissue samples collected from them as well as animals euthanized during the
      trial were evaluated for histological lesions. The warthogs, which were
      clinically normal throughout the study, developed histological lesions that were
      inconsistently present and sometimes subtle. Three individuals, including one in
      contact control, developed distinct lympho-plasmacytic cuffing in their brains.
      Subtle lesions included scant lympho-plasmacytic infiltration of various organs,
      occasionally accompanied by perivascular cuffing. In contrast, the bushpigs
      developed overt clinical signs similar to CSF in domestic pigs. Four of six
      animals, including two in-contact controls, died or were euthanized during the
      trial. On postmortem examination, intestinal necrosis and ulceration, purulent
      rhinitis and pneumonia were present. Affected animals developed lymphoid necrosis
      and depletion whilst surviving individuals showed perivascular cuffing in
      multiple organs. From the present work, we conclude that these wild Suidae are
      susceptible to CSF virus and intra-species transmission under experimental
      conditions can occur.

PMID- 21176122
TI  - Information from cochlear potentials and genetic mutations helps localize the
      lesion site in auditory neuropathy.
AB  - Auditory neuropathy (AN) is a disorder characterized by disruption of auditory
      nerve activity resulting from lesions involving the auditory nerve (postsynaptic
      AN), inner hair cells and/or the synapses with auditory nerve terminals
      (presynaptic AN). Affected subjects show impairment of speech perception beyond
      that expected for the hearing loss, abnormality of auditory brainstem potentials
      and preserved outer hair-cell activities. Furthermore, AN can be identified
      either as an isolated disorder or as an associated disorder with multisystem
      involvement including peripheral and optic neuropathies (non-isolated AN).
      Mutations in several nuclear and mitochondrial genes have been identified as
      underlying these forms of AN. Recently, new genes have been identified as
      involved in both isolated (DIAPH3, OTOF) and non-isolated AN (OPA1). Moreover,
      abnormal cochlear potentials have been recorded from patients with specific gene
      mutations by using acoustic stimuli or electrical stimulation through cochlear
      implant. In this review, different types of genetically based auditory
      neuropathies are discussed and the proposed molecular mechanisms underlying AN
      are reviewed.

PMID- 21176123
TI  - How many general and inflammatory variables need to be fulfilled when defining
      sepsis due to the 2003 SCCM/ESICM/ACCP/ATS/SIS definitions in critically ill
      surgical patients: a retrospective observational study.
AB  - BACKGROUND: It has never been specified how many of the extended general and
      inflammatory variables of the 2003 SCCM/ESICM/ACCP/ATS/SIS consensus sepsis
      definitions are mandatory to define sepsis. OBJECTIVES: To find out how many of
      these variables are needed to identify almost all patients with septic shock.
      METHODS: Retrospective observational single-centre study in
      postoperative/posttraumatic patients admitted to an University adult ICU. The
      survey looked at 1355 admissions, from 01/2007 to 12/2008, that were monitored
      daily computer-assisted for the eight general and inflammatory variables
      temperature, heart rate, respiratory rate, significant edema, positive fluid
      balance, hyperglycemia, white blood cell count and C-reactive protein. A total of
      507 patients with infections were classified based on the first day with the
      highest diagnostic category of sepsis during their stay using a cut-off of 1/8
      variables compared with the corresponding classification based on a cut-off of 2,
      3, 4, 5, 6, 7 or 8/8 variables. RESULTS: Applying cut-offs of 1/8 up to 8/8
      variables resulted in a decreased detection rate of cases with septic shock,
      i.e., from 106, 105, 103, 93, 65, 21, 3 to 0. The mortality rate increased up to
      a cut-off of 6/8 variables, i.e., 31% (33/106), 31% (33/105), 31% (32/103), 32%
      (30/93), 38% (25/65), 43% (9/21), 33% (1/3) and 0% (0/0). CONCLUSIONS:
      Frequencies and mortality rates of diagnostic categories of sepsis differ
      depending on the cut-off for general and inflammatory variables. A cut-off of 3/8
      variables is needed to identify almost all patients with septic shock who may
      benefit from optimal treatment.

PMID- 21176124
TI  - New insights into protein-protein interaction data lead to increased estimates of
      the S. cerevisiae interactome size.
AB  - BACKGROUND: As protein interactions mediate most cellular mechanisms, protein
      protein interaction networks are essential in the study of cellular processes.
      Consequently, several large-scale interactome mapping projects have been
      undertaken, and protein-protein interactions are being distilled into databases
      through literature curation; yet protein-protein interaction data are still far
      from comprehensive, even in the model organism Saccharomyces cerevisiae.
      Estimating the interactome size is important for evaluating the completeness of
      current datasets, in order to measure the remaining efforts that are required.
      RESULTS: We examined the yeast interactome from a new perspective, by taking into
      account how thoroughly proteins have been studied. We discovered that the set of
      literature-curated protein-protein interactions is qualitatively different when
      restricted to proteins that have received extensive attention from the scientific
      community. In particular, these interactions are less often supported by yeast
      two-hybrid, and more often by more complex experiments such as biochemical
      activity assays. Our analysis showed that high-throughput and literature-curated
      interactome datasets are more correlated than commonly assumed, but that this
      bias can be corrected for by focusing on well-studied proteins. We thus propose a
      simple and reliable method to estimate the size of an interactome, combining
      literature-curated data involving well-studied proteins with high-throughput
      data. It yields an estimate of at least 37, 600 direct physical protein-protein
      interactions in S. cerevisiae. CONCLUSIONS: Our method leads to higher and more
      accurate estimates of the interactome size, as it accounts for interactions that
      are genuine yet difficult to detect with commonly-used experimental assays. This
      shows that we are even further from completing the yeast interactome map than
      previously expected.

PMID- 21176126
TI  - Comparative proteomic analysis of Salmonella enterica serovar Typhimurium ppGpp
      deficient mutant to identify a novel virulence protein required for intracellular
      survival in macrophages.
AB  - BACKGROUND: The global ppGpp-mediated stringent response in pathogenic bacteria
      plays an important role in the pathogenesis of bacterial infections. In
      Salmonella enterica serovar Typhimurium (S. Typhimurium), several genes,
      including virulence genes, are regulated by ppGpp when bacteria are under the
      stringent response. To understand the control of virulence genes by ppGpp in S.
      Typhimurium, agarose 2-dimensional electrophoresis (2-DE) combined with mass
      spectrometry was used and a comprehensive 2-DE reference map of amino acid
      starved S. Typhimurium strain SH100, a derivative of ATCC 14028, was established.
      RESULTS: Of the 366 examined spots, 269 proteins were successfully identified.
      The comparative analysis of the wild-type and ppGpp0 mutant strains revealed 55
      proteins, the expression patterns of which were affected by ppGpp. Using a mouse
      infection model, we further identified a novel virulence-associated factor,
      STM3169, from the ppGpp-regulated and Salmonella-specific proteins. In addition,
      Salmonella strains carrying mutations in the gene encoding STM3169 showed growth
      defects and impaired growth within macrophage-like RAW264.7 cells. Furthermore,
      we found that expression of stm3169 was controlled by ppGpp and SsrB, a response
      regulator of the two-component system located on Salmonella pathogenicity island
      2. CONCLUSIONS: A proteomic approach using a 2-DE reference map can prove a
      powerful tool for analyzing virulence factors and the regulatory network involved
      in Salmonella pathogenesis. Our results also provide evidence of a global
      response mediated by ppGpp in S. enterica.

PMID- 21176127
TI  - Population expansion in the North African late Pleistocene signalled by
      mitochondrial DNA haplogroup U6.
AB  - BACKGROUND: The archaeology of North Africa remains enigmatic, with questions of
      population continuity versus discontinuity taking centre-stage. Debates have
      focused on population transitions between the bearers of the Middle Palaeolithic
      Aterian industry and the later Upper Palaeolithic populations of the Maghreb, as
      well as between the late Pleistocene and Holocene. RESULTS: Improved resolution
      of the mitochondrial DNA (mtDNA) haplogroup U6 phylogeny, by the screening of 39
      new complete sequences, has enabled us to infer a signal of moderate population
      expansion using Bayesian coalescent methods. To ascertain the time for this
      expansion, we applied both a mutation rate accounting for purifying selection and
      one with an internal calibration based on four approximate archaeological dates:
      the settlement of the Canary Islands, the settlement of Sardinia and its internal
      population re-expansion, and the split between haplogroups U5 and U6 around the
      time of the first modern human settlement of the Near East. CONCLUSIONS: A
      Bayesian skyline plot placed the main expansion in the time frame of the Late
      Pleistocene, around 20 ka, and spatial smoothing techniques suggested that the
      most probable geographic region for this demographic event was to the west of
      North Africa. A comparison with U6's European sister clade, U5, revealed a
      stronger population expansion at around this time in Europe. Also in contrast
      with U5, a weak signal of a recent population expansion in the last 5,000 years
      was observed in North Africa, pointing to a moderate impact of the late Neolithic
      on the local population size of the southern Mediterranean coast.

PMID- 21176129
TI  - Meeting report: 3rd international workshop on insulin & cancer heidelberg,
      Germany, october 30-31, 2010.
AB  - The 3rd International Workshop on Insulin & Cancer was held on October 30-31,
      2010 at the German Cancer Research Centre in Heidelberg/Germany. The topics
      followed-up the discussions of the previous workshops: possible differences in
      mitogenicity between natural insulin and genetically engineered insulin
      derivatives (insulin analogues), as shown by laboratory studies and epidemiologic
      studies alike; molecular studies on the links between metabolic and mitogenic
      effects of insulin, and of hyperinsulinaemia in particular; epidemiologic
      evidence of interferences between insulin and other hormones, particularly sex
      hormones, and obesity-associated cancer; the involvement of inflammatory
      cytokines produced by fat tissue in obesity-associated cancer; aspects of drug
      design (binding drugs to albumin) and, last but not least, detection and
      investigation of circulating cancer cells.

PMID- 21176130
TI  - Retraction: End-of-life discontinuation of destination therapy with cardiac and
      ventilatory support medical devices: physician-assisted death or allowing the
      patient to die? BMC Medical Ethics 2010, 11:15.

PMID- 21176128
TI  - Polysaccharides from the root of Angelica sinensis promotes hematopoiesis and
      thrombopoiesis through the PI3K/AKT pathway.
AB  - BACKGROUND: Dozens of Traditional Chinese Medicine (TCM) formulas have been used
      for promotion of "blood production" for centuries, and we are interested in
      developing novel thrombopoietic medicines from these TCMs. Our previous studies
      have demonstrated the hematopoietic effects of DangGui BuXue Tong (DBT), a
      formula composed of Radix Angelicae Sinensis and Radix Astragali in animal and
      cellular models. As a step further to identify and characterize the active
      chemical components of DBT, we tested the hematopoietic and particularly,
      thrombopoietic effects of polysaccharide-enriched fractions from the root of
      Radix Angelicae Sinensis (APS) in this study. METHODS: A myelosuppression mouse
      model was treated with APS (10 mg/kg/day). Peripheral blood cells from APS,
      thrombopoietin and vehicle-treated samples were then counted at different time
      points. Using the colony-forming unit (CFU) assays, we determined the effects of
      APS on the proliferation and differentiation of hematopoietic stem/progenitor
      cells and megakaryocytic lineages. Using a megakaryocytic cell line M-07e as
      model, we analyzed the cellular apoptosis progression with and without APS
      treatment by Annexin V, Mitochondrial Membrane Potential and Caspase 3 assays.
      Last, the anti-apoptotic effect of APS on cells treated with Ly294002, a
      Phosphatidylinositol 3-Kinse inhibitor (PI3K) was also tested. RESULTS: In animal
      models, APS significantly enhanced not only the recovery of platelets, other
      blood cells and their progenitor cells, but also the formation of Colony Forming
      Unit (CFU). In M-07e cells, we observed the anti-apoptotic effect of APS.
      Treatment by Ly294002 alone increased the percentage of cells undergoing
      apoptosis. However, addition of APS to Ly294002-treated cells significantly
      reduced the percentage of cells undergoing apoptosis. CONCLUSIONS: APS promotes
      hematopoiesis and thrombopoiesis in the mouse model. This effect likely resulted
      from the anti-apoptosis activity of APS and is likely to involve the PI3K/AKT
      pathway.

PMID- 21176131
TI  - The feasibility of introducing rapid diagnostic tests for malaria in drug shops
      in Uganda.
AB  - BACKGROUND: National malaria control programmes and international agencies are
      keen to scale-up the use of effective rapid diagnostic tests (RDTs) for malaria.
      The high proportion of the Ugandan population seeking care at drug shops makes
      these outlets attractive as providers of malaria RDTs. However, there is no
      precedent for blood testing at drug shops and little is known about how such
      tests might be perceived and used. Understanding use of drug shops by communities
      in Uganda is essential to inform the design of interventions to introduce RDTs.
      METHODS: We conducted a qualitative study, with 10 community focus group
      discussions, and 18 in-depth interviews with drug shop attendants, health workers
      and district health officials. The formative study was carried out in Mukono
      district, central Uganda an area of high malaria endemicity from May-July 2009.
      RESULTS: Drug shops were perceived by the community as important in treating
      malaria and there was awareness among most drug sellers and the community that
      not all febrile illnesses were malaria. The idea of introducing RDTs for malaria
      diagnosis in drug shops was attractive to most respondents. It was anticipated
      that RDTs would improve access to effective treatment of malaria, offset high
      costs associated with poor treatment, and avoid irrational drug use. However,
      communities did express fear that drug shops would overprice RDTs, raising the
      overall treatment cost for malaria. Other fears included poor adherence to the
      RDT result, reuse of RDTs leading to infections and fear that RDTs would be used
      to test for human immune deficiency virus (HIV). All drug shops visited had no
      record on patient data and referral of cases to health units was noted to be
      poor. CONCLUSION: These results not only provide useful lessons for implementing
      the intervention study but have wide implications for scaling up malaria
      treatment in drug shops.

PMID- 21176132
TI  - "Immortal but frightened"-smoking adolescents' perceptions on smoking uptake and
      prevention.
AB  - BACKGROUND: To curb the tobacco epidemic a combination of comprehensive
      interventions are needed at different levels. Smoking uptake is a multi-factorial
      process that includes societal factors as well as social and individual
      characteristics. An understanding of the process is essential in order to model
      interventions. The aim of this study was to explore the role of smoking for young
      smokers by focusing on the mechanisms that facilitate young people starting to
      smoke as well as what could have prevented them from starting. METHODS: A
      qualitative research design using focus group discussions was chosen as the basis
      for a content analysis approach. Eight focus groups were conducted with five to
      six participants in each (four groups with boys, four with girls). The informants
      were purposively selected to represent smokers in the age range of 15-16 years
      within the county. The total number of group participants was 44; 21 were girls
      and 23 boys. The study was performed at 7-9th grade schools in Vasterbotten
      County in northern Sweden. RESULTS: Three themes related to different aspects of
      youth smoking behaviour emerged from the analysis. Theme 1) "gaining control"
      reflects what makes young people become smokers; theme 2) "becoming a part of the
      self" focuses on what facilitates youths to start smoking; theme 3) "concerned
      adults make a difference" indicates what may prevent them from starting.
      CONCLUSION: Young smokers described starting to smoke as a means of gaining
      control of feelings and situations during early adolescence. Smoking adolescents
      expect adults to intervene against smoking. Close relations with concerned adults
      could be a reason for less frequent smoking or trying to quit smoking.
      Interventions aimed at normative changes, with consistent messages from both
      schools and parents about the negative aspects of tobacco seem to be a feasible
      approach for preventing youth from using tobacco.

PMID- 21176133
TI  - Obesity related methylation changes in DNA of peripheral blood leukocytes.
AB  - BACKGROUND: Despite evidence linking obesity to impaired immune function, little
      is known about the specific mechanisms. Because of emerging evidence that immune
      responses are epigenetically regulated, we hypothesized that DNA methylation
      changes are involved in obesity induced immune dysfunction and aimed to identify
      these changes. METHOD: We conducted a genome wide methylation analysis on seven
      obese cases and seven lean controls aged 14 to 18 years from extreme ends of the
      obesity distribution and performed further validation of six CpG sites from six
      genes in 46 obese cases and 46 lean controls aged 14 to 30 years. RESULTS: In
      comparison with the lean controls, we observed one CpG site in the UBASH3A gene
      showing higher methylation levels and one CpG site in the TRIM3 gene showing
      lower methylation levels in the obese cases in both the genome wide step (P = 5 *
      10(-6) and P = 2 * 10(-5) for the UBASH3A and the TRIM3 gene respectively) and
      the validation step (P = 0.008 and P = 0.001 for the UBASH3A and the TRIM3 gene
      respectively). CONCLUSIONS: Our results provide evidence that obesity is
      associated with methylation changes in blood leukocyte DNA. Further studies are
      warranted to determine the causal direction of this relationship as well as
      whether such methylation changes can lead to immune dysfunction.

PMID- 21176134
TI  - Kernel based methods for accelerated failure time model with ultra-high
      dimensional data.
AB  - BACKGROUND: Most genomic data have ultra-high dimensions with more than 10,000
      genes (probes). Regularization methods with L1 and L(p) penalty have been
      extensively studied in survival analysis with high-dimensional genomic data.
      However, when the sample size n << m (the number of genes), directly identifying
      a small subset of genes from ultra-high (m > 10, 000) dimensional data is time
      consuming and not computationally efficient. In current microarray analysis, what
      people really do is select a couple of thousands (or hundreds) of genes using
      univariate analysis or statistical tests, and then apply the LASSO-type penalty
      to further reduce the number of disease associated genes. This two-step procedure
      may introduce bias and inaccuracy and lead us to miss biologically important
      genes. RESULTS: The accelerated failure time (AFT) model is a linear regression
      model and a useful alternative to the Cox model for survival analysis. In this
      paper, we propose a nonlinear kernel based AFT model and an efficient variable
      selection method with adaptive kernel ridge regression. Our proposed variable
      selection method is based on the kernel matrix and dual problem with a much
      smaller n x n matrix. It is very efficient when the number of unknown variables
      (genes) is much larger than the number of samples. Moreover, the primal variables
      are explicitly updated and the sparsity in the solution is exploited.
      CONCLUSIONS: Our proposed methods can simultaneously identify survival associated
      prognostic factors and predict survival outcomes with ultra-high dimensional
      genomic data. We have demonstrated the performance of our methods with both
      simulation and real data. The proposed method performs superbly with limited
      computational studies.

PMID- 21176135
TI  - Peroxisome proliferator-activated receptor delta +294T > C polymorphism and serum
      lipid levels in the Guangxi Bai Ku Yao and Han populations.
AB  - BACKGROUND: The association of peroxisome proliferator-activated receptor delta
      (PPARD) +294T > C polymorphism and serum lipid levels is inconsistent in several
      previous studies. Bai Ku Yao is an isolated subgroup of the Yao minority in
      China. The present study was undertaken to detect the association of PPARD +294T
      > C (rs2016520) polymorphism and several environmental factors with serum lipid
      levels in the Guangxi Bai Ku Yao and Han populations. METHODS: A total of 609
      subjects of Bai Ku Yao and 573 participants of Han Chinese were randomly selected
      from our previous stratified randomized cluster samples. Genotyping of the PPARD
      +294T > C polymorphism was performed by polymerase chain reaction and restriction
      fragment length polymorphism combined with gel electrophoresis, and then
      confirmed by direct sequencing. RESULTS: The levels of serum total cholesterol
      (TC), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) AI and
      ApoB were lower in Bai Ku Yao than in Han (P < 0.001 for all). The frequency of T
      and C alleles was 77.50% and 22.50% in Bai Ku Yao, and 72.43% and 27.57% in Han
      (P < 0.01); respectively. The frequency of TT, TC and CC genotypes was 60.59%,
      33.83% and 5.53% in Bai Ku Yao, and 52.18%, 40.50% and 7.32% in Han (P < 0.05);
      respectively. The subjects with CC genotype in Bai Ku Yao had higher serum LDL-C
      and ApoB levels and lower the ratio of ApoAI to ApoB than the subjects with TT
      and TC genotypes in females but not in males. The C allele carriers in Han had
      higher serum TC levels in males (P < 0.01) and ApoB levels in females (P < 0.05)
      than the C allele noncarriers. Serum TC and ApoB levels were correlated with
      genotypes in Han (P < 0.05 for each) but not in Bai Ku Yao. Serum lipid
      parameters were also correlated with sex, age, body mass index, alcohol
      consumption, cigarette smoking, and blood pressure in both ethnic groups.
      CONCLUSIONS: These results suggest that the association of PPARD +294T > C
      polymorphism and serum lipid levels is different between the Bai Ku Yao and Han
      populations. The discrepancy between the two ethnic groups might partly result
      from different PPARD +294T > C polymorphism or PPARD gene-environmental
      interactions.

PMID- 21176136
TI  - Epigenetics and obesity: the devil is in the details.
AB  - Obesity is a complex disease with multiple well-defined risk factors.
      Nevertheless, susceptibility to obesity and its sequelae within obesogenic
      environments varies greatly from one person to the next, suggesting a role for
      gene * environment interactions in the etiology of the disorder. Epigenetic
      regulation of the human genome provides a putative mechanism by which specific
      environmental exposures convey risk for obesity and other human diseases and is
      one possible mechanism that underlies the gene * environment/treatment
      interactions observed in epidemiological studies and clinical trials. A study
      published in BMC Medicine this month by Wang et al. reports on an examination of
      DNA methylation in peripheral blood leukocytes of lean and obese adolescents,
      comparing methylation patterns between the two groups. The authors identified two
      genes that were differentially methylated, both of which have roles in immune
      function. Here we overview the findings from this study in the context of those
      emerging from other recent genetic and epigenetic studies, discuss the strengths
      and weaknesses of the study and speculate on the future of epigenetics in chronic
      disease research.

PMID- 21176137
TI  - A longitudinal study of chiropractic use among older adults in the United States.
AB  - BACKGROUND: Longitudinal patterns of chiropractic use in the United States,
      particularly among Medicare beneficiaries, are not well documented. Using a
      nationally representative sample of older Medicare beneficiaries we describe the
      use of chiropractic over fifteen years, and classify chiropractic users by annual
      visit volume. We assess the characteristics that are associated with chiropractic
      use versus nonuse, as well as between different levels of use. METHODS: We
      analyzed data from two linked sources: the baseline (1993-1994) interview
      responses of 5,510 self-respondents in the Survey on Assets and Health Dynamics
      Among the Oldest Old (AHEAD), and their Medicare claims from 1993 to 2007.
      Binomial logistic regression was used to identify factors associated with
      chiropractic use versus nonuse, and conditional upon use, to identify factors
      associated with high volume relative to lower volume use. RESULTS: There were 806
      users of chiropractic in the AHEAD sample yielding a full period prevalence for
      1993-2007 of 14.6%. Average annual prevalence between 1993 and 2007 was 4.8% with
      a range from 4.1% to 5.4%. Approximately 42% of the users consumed chiropractic
      services only in a single calendar year while 38% used chiropractic in three or
      more calendar years. Chiropractic users were more likely to be women, white,
      overweight, have pain, have multiple comorbid conditions, better self-rated
      health, access to transportation, higher physician utilization levels, live in
      the Midwest, and live in an area with fewer physicians per capita. Among
      chiropractic users, 16% had at least one year in which they exceeded Medicare's
      "soft cap" of 12 visits per calendar year. These over-the-cap users were more
      likely to have arthritis and mobility limitations, but were less likely to have a
      high school education. Additionally, these over-the-cap individuals accounted for
      58% of total chiropractic claim volume. High volume users saw chiropractors the
      most among all types of providers, even more than family practice and internal
      medicine combined. CONCLUSION: There is substantial heterogeneity in the patterns
      of use of chiropractic services among older adults. In spite of the variability
      of use patterns, however, there are not many characteristics that distinguish
      high volume users from lower volume users. While high volume users accounted for
      a significant portion of claims, the enforcement of a hard cap on annual visits
      by Medicare would not significantly decrease overall claim volume. Further
      research to understand the factors causing high volume chiropractic utilization
      among older Americans is warranted to discern between patterns of "need" and
      patterns of "health maintenance".

PMID- 21176138
TI  - The CTCF insulator protein forms an unusual DNA structure.
AB  - BACKGROUND: The CTCF insulator protein is a highly conserved zinc finger protein
      that has been implicated in many aspects of gene regulation and nuclear
      organization. The protein has been hypothesized to organize the human genome by
      forming DNA loops. RESULTS: In this paper, we report biochemical evidence to
      support the role for CTCF in forming DNA loops. We have measured DNA bending by
      CTCF at the chicken HS4 beta-globin FII insulator element in vitro and have
      observed a unique DNA structure with aberrant electrophoretic mobility which we
      believe to be a DNA loop. CTCF is able to form this unusual DNA structure at two
      other binding sites: the c-myc P2 promoter and the chicken F1 lysozyme gene
      silencer. We also demonstrate that the length though not the sequence of the DNA
      downstream of the binding site is important for the ability of CTCF to form this
      unusual DNA structure. We hypothesize that a single CTCF protein molecule is able
      to act as a "looper" possibly through the use of several of its zinc fingers.
      CONCLUSIONS: CTCF is able to form an unusual DNA structure through the zinc
      finger domain of the protein. This unusual DNA structure is formed in a
      directional manner by the CTCF protein. The findings described in this paper
      suggest mechanisms by which CTCF is able to form DNA loops, organize the
      mammalian genome and function as an insulator protein.

PMID- 21176139
TI  - Rapidly progressive polyneuropathy due to dry beriberi in a man: a case report.
AB  - INTRODUCTION: We describe a case of rapidly progressive and severely debilitating
      polyneuropathy in a patient with confirmed hypovitaminosis B1, consistent with
      dry beriberi. Crucially, this is a treatable condition, although sometimes with
      incomplete recovery, but it is probably under-recognized yet increasingly common
      given increasing levels of alcohol abuse in the western world. CASE PRESENTATION:
      A 49-year-old Caucasian British man presented with progressive weakness of both
      lower limbs of approximately seven months' duration. He noted difficulty climbing
      stairs. He also complained of lethargy, and loss of muscle bulk, including his
      thighs. He had a history of type 2 diabetes mellitus and admitted prior alcohol
      abuse but denied excessive alcohol intake in the five years prior to
      presentation. Initial clinical and neurophysiological examinations were
      consistent with a mild peripheral neuropathy and probable proximal myopathy.
      However, over the subsequent four months he evolved a marked tetraparesis, with
      profound sensory disturbance of all limbs. Repeat neurophysiology revealed a
      widespread polyneuropathy with extensive acute and sub-acute denervation changes
      in all four limbs, and reduced or absent sensory nerve action potentials.
      Hypovitaminosis B1 was confirmed (45 nmol/L, reference range 66-200 nmol/L). His
      rapid clinical deterioration was in keeping with dry beriberi. He was treated
      with thiamine. Subsequent follow-up revealed slow but significant improvement,
      such that by 15-16 months from the initial onset of symptoms, and approximately
      six months after the onset of his marked tetraparesis, he was able to stand
      independently and was gradually gaining confidence in walking pending a period of
      in-patient neurorehabilitation. CONCLUSION: A potentially wide differential
      diagnosis exists for this type of presentation. Confirming hypovitaminosis B1 by
      requesting the assay prior to vitamin replacement ensures accurate diagnosis and
      appropriate ongoing treatment. An increasingly high index of suspicion is likely
      to be required in the context of increasing levels of alcohol abuse in the
      western world and the possible increasing prevalence of dry beriberi.

PMID- 21176140
TI  - PICK1 regulates the trafficking of ASIC1a and acidotoxicity in a BAR domain lipid
      binding-dependent manner.
AB  - BACKGROUND: Acid-sensing ion channel 1a (ASIC1a) is the major ASIC subunit
      determining acid-activated currents in brain neurons. Recent studies show that
      ASIC1a play critical roles in acid-induced cell toxicity. While these studies
      raise the importance of ASIC1a in diseases, mechanisms for ASIC1a trafficking are
      not well understood. Interestingly, ASIC1a interacts with PICK1 (protein
      interacting with C-kinase 1), an intracellular protein that regulates trafficking
      of several membrane proteins. However, whether PICK1 regulates ASIC1a surface
      expression remains unknown. RESULTS: Here, we show that PICK1 overexpression
      increases ASIC1a surface level. A BAR domain mutant of PICK1, which impairs its
      lipid binding capability, blocks this increase. Lipid binding of PICK1 is also
      required for PICK1-induced clustering of ASIC1a. Consistent with the effect on
      ASIC1a surface levels, PICK1 increases ASIC1a-mediated acidotoxicity and this
      effect requires both the PDZ and BAR domains of PICK1. CONCLUSIONS: Taken
      together, our results indicate that PICK1 regulates trafficking and function of
      ASIC1a in a lipid binding-dependent manner.

PMID- 21176141
TI  - Genetic diversity of selected genes that are potentially economically important
      in feral sheep of New Zealand.
AB  - BACKGROUND: Feral sheep are considered to be a source of genetic variation that
      has been lost from their domestic counterparts through selection. METHODS: This
      study investigates variation in the genes KRTAP1-1, KRT33, ADRB3 and DQA2 in
      Merino-like feral sheep populations from New Zealand and its offshore islands.
      These genes have previously been shown to influence wool, lamb survival and
      animal health. RESULTS: All the genes were polymorphic, but no new allele was
      identified in the feral populations. In some of these populations, allele
      frequencies differed from those observed in commercial Merino sheep and other
      breeds found in New Zealand. Heterozygosity levels were comparable to those
      observed in other studies on feral sheep. Our results suggest that some of the
      feral populations may have been either inbred or outbred over the duration of
      their apparent isolation. CONCLUSION: The variation described here allows us to
      draw some conclusions about the likely genetic origin of the populations and
      selective pressures that may have acted upon them, but they do not appear to be a
      source of new genetic material, at least for these four genes.

PMID- 21176142
TI  - Analysis of Escherichia coli O157 clinical isolates by multilocus sequence
      typing.
AB  - BACKGROUND: Although many strain typing methods exist for pathogenic Escherichia
      coli, most have drawbacks in terms of resolving power, interpretability, or
      scalability. For this reason, multilocus sequence typing (MLST) is an appealing
      alternative especially when applied to the typing of temporal and spatially
      separated isolates. This method relies on an unambiguous DNA sequence analysis of
      nucleotide polymorphisms in housekeeping genes and has shown a high degree of
      intraspecies discriminatory power for bacterial and fungal pathogens. RESULTS:
      Here we used the MLST method to study the genetic diversity among E. coli O157
      isolates collected from humans from two different locations of USA over a period
      of several years (2000-2008). MLST analysis of 33 E. coli O157 patient isolates
      using the eBurst algorithm distinguished 26 different sequence types (STs), which
      were clustered into two clonal groups and 11 singletons. The predominant ST was
      ST2, which consisted of 5 isolates (14.28%) followed by ST1 (11.42%). All the
      isolates under clonal group I exhibited a virtually similar virulence profile
      except for two strains, which tested negative for the presence of stx genes. The
      isolates that were assigned to clonal group II in addition to the 11 singletons
      were found to be phylogenetically distant from clonal group I. Furthermore, we
      observed a positive correlation between the virulence profile of the isolates and
      their clonal origin. CONCLUSIONS: Our data suggests the presence of genetic
      diversity among E. coli O157 isolates from humans shows no measurable correlation
      to the geographic origin of the isolates.

PMID- 21176143
TI  - Analysis of ovarian tumor pathology by Fourier Transform Infrared Spectroscopy.
AB  - BACKGROUND: Ovarian cancer is the second most common cancer among women and the
      leading cause of death among gynecologic malignancies. In recent years, infrared
      (IR) spectroscopy has gained attention as a simple and inexpensive method for the
      biomedical study of several diseases. In the present study infrared spectra of
      normal and malignant ovarian tissues were recorded in the 650 cm-1 to 4000 cm-1
      region. METHODS: Post surgical tissue samples were taken from the normal and
      tumor sections of the tissue. Fourier Transform Infrared (FTIR) data on twelve
      cases of ovarian cancer with different grades of malignancy from patients of
      different age groups were analyzed. RESULTS: Significant spectral differences
      between the normal and the ovarian cancerous tissues were observed. In particular
      changes in frequency and intensity in the spectral region of protein, nucleic
      acid and lipid vibrational modes were observed. It was evident that the sample-to
      sample or patient-to-patient variations were small and the spectral differences
      between normal and diseased tissues were reproducible. CONCLUSION: The measured
      spectroscopic features, which are the spectroscopic fingerprints of the tissues,
      provided the important differentiating information about the malignant and normal
      tissues. The findings of this study demonstrate the possible use of infrared
      spectroscopy in differentiating normal and malignant ovarian tissues.

PMID- 21176144
TI  - Randomized trial evaluating serial protein C levels in severe sepsis patients
      treated with variable doses of drotrecogin alfa (activated).
AB  - INTRODUCTION: Serial alterations in protein C levels appear to correlate with
      disease severity in patients with severe sepsis, and it may be possible to tailor
      severe sepsis therapy with the use of this biomarker. The purpose of this study
      was to evaluate the dose and duration of drotrecogin alfa (activated) treatment
      using serial measurements of protein C compared to standard therapy in patients
      with severe sepsis. METHODS: This was a phase 2 multicenter, randomized, double
      blind, controlled study. Adult patients with two or more sepsis-induced organ
      dysfunctions were enrolled. Protein C deficient patients were randomized to
      standard therapy (24 MUg/kg/hr infusion for 96 hours) or alternative therapy
      (higher dose and/or variable duration; 24/30/36 MUg/kg/hr for 48 to 168 hours).
      The primary outcome was a change in protein C level in the alternative therapy
      group, between study Day 1 and Day 7, compared to standard therapy. RESULTS: Of
      557 patients enrolled, 433 patients received randomized therapy; 206 alternative,
      and 227 standard. Baseline characteristics of the groups were largely similar.
      The difference in absolute change in protein C from Day 1 to Day 7 between the
      two therapy groups was 7% (P = 0.011). Higher doses and longer infusions were
      associated with a more pronounced increase in protein C level, with no serious
      bleeding events. The same doses and longer infusions were associated with a
      larger increase in protein C level; higher rates of serious bleeding when groups
      received the same treatment; but no clear increased risk of bleeding during the
      longer infusion. This group also experienced a higher mortality rate; however,
      there was no clear link to infusion duration. CONCLUSIONS: The study met its
      primary objective of increased protein C levels in patients receiving alternative
      therapy demonstrating that variable doses and/or duration of drotrecogin alfa
      (activated) can improve protein C levels, and also provides valuable information
      for incorporation into potential future studies. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT00386425.

PMID- 21176145
TI  - A sensitive and bright single-cell resolution live imaging reporter of Wnt/beta
      catenin signaling in the mouse.
AB  - BACKGROUND: Understanding the dynamic cellular behaviors and underlying molecular
      mechanisms that drive morphogenesis is an ongoing challenge in biology. Live
      imaging provides the necessary methodology to unravel the synergistic and
      stereotypical cell and molecular events that shape the embryo. Genetically
      encoded reporters represent an essential tool for live imaging. Reporter strains
      can be engineered by placing cis-regulatory elements of interest to direct the
      expression of a desired reporter gene. In the case of canonical Wnt signaling,
      also referred to as Wnt/beta-catenin signaling, since the downstream
      transcriptional response is well understood, reporters can be designed that
      reflect sites of active Wnt signaling, as opposed to sites of gene transcription,
      as is the case with many fluorescent reporters. However, even though several
      transgenic Wnt/beta-catenin reporter strains have been generated, to date, none
      provides the single-cell resolution favored for live imaging studies. RESULTS: We
      have placed six copies of a TCF/Lef responsive element and an hsp68 minimal
      promoter in front of a fluorescent protein fusion comprising human histone H2B to
      GFP and used it to generate a strain of mice that would report Wnt/beta-catenin
      signaling activity. Characterization of developmental and adult stages of the
      resulting TCF/Lef:H2B-GFP strain revealed discrete and specific expression of the
      transgene at previously characterized sites of Wnt/beta-catenin signaling. In
      support of the increased sensitivity of the TCF/Lef:H2B-GFP reporter, additional
      sites of Wnt/beta-catenin signaling not documented with other reporters but
      identified through genetic and embryological analysis were observed. Furthermore,
      the sub-cellular localization of the reporter minimized reporter perdurance, and
      allowed visualization and tracking of individual cells within a cohort, so
      facilitating the detailed analysis of cell behaviors and signaling activity
      during morphogenesis. CONCLUSION: By combining the Wnt activity read-out
      efficiency of multimerized TCF/Lef DNA binding sites, together with the high
      resolution imaging afforded by subcellularly-localized fluorescent fusion
      proteins such as H2B-GFP, we have created a mouse transgenic line that faithfully
      recapitulates Wnt signaling activity at single-cell resolution. The TCF/Lef:H2B
      GFP reporter represents a unique tool for live imaging the in vivo processes
      triggered by Wnt/beta-catenin signaling, and thus should help the formulation of
      a high-resolution understanding of the serial events that define the
      morphogenetic process regulated by this signaling pathway.

PMID- 21176146
TI  - HIV and hepatitis B and C incidence rates in US correctional populations and high
      risk groups: a systematic review and meta-analysis.
AB  - BACKGROUND: High Human Immunodeficiency Virus (HIV) prevalence and high risk
      behaviors have been well documented within United States (US) correctional
      systems. However, uncertainty remains regarding the extent to which placing
      people in prison or jail increases their risk of HIV infection, and regarding
      which inmate populations experience an increased incidence of HIV. Describing
      these dynamics more clearly is essential to understanding how inmates and former
      detainees may be a source for further spread of HIV to the general US population.
      METHODS: The authors conducted a systematic review and meta-analysis of studies
      describing HIV incidence in US correctional facility residents and, for
      comparison, in high risk groups for HIV infection, such as non-incarcerated
      intravenous drug users (IVDU) and men who have sex with men (MSM) in the US. HIV
      incidence rates were further compared with Hepatitis B and Hepatitis C Virus
      rates in these same populations. RESULTS: Thirty-six predominantly prospective
      cohort studies were included. Across all infection outcomes, continuously
      incarcerated inmates and treatment recruited IVDU showed the lowest incidence,
      while MSM and street recruited IVDU showed the highest. HIV incidence was highest
      among inmates released and re-incarcerated. Possible sources of heterogeneity
      identified among HIV studies were risk population and race. CONCLUSIONS: Although
      important literature gaps were found, current evidence suggests that policies and
      interventions for HIV prevention in correctional populations should prioritize
      curtailing risk of infection during the post-release period. Future research
      should evaluate HIV incidence rates in inmate populations, accounting for
      proportion of high risk sub-groups.

PMID- 21176147
TI  - Tumor location and patient characteristics of colon and rectal adenocarcinomas in
      relation to survival and TNM classes.
AB  - BACKGROUND: Old age at diagnosis is associated with poor survival in colorectal
      cancer (CRC) for unknown reasons. Recent data show that colonoscopy is efficient
      in preventing left-sided cancers only. We examine the association of Tumor Node
      Metastasis (TNM) classes with diagnostic age and patient characteristics.
      METHODS: The Swedish Family-Cancer Database has data on TNM classes on 6,105 CRC
      adenocarcinoma patients. Ordinal logistic regression analysis was performed to
      model tumor characteristics according to age at diagnosis, tumor localization,
      gender, socioeconomic status, medical region and family history. The results were
      compared to results from survival analysis. RESULTS: The only parameters
      systematically associated with TNM classes were age and tumor localization. Young
      age at diagnosis was a risk factor for aggressive CRC, according to stage, N and
      M with odds ratios (ORs) ranging from 1.80 to 1.93 for diagnosis before age 50
      years compared to diagnosis at 80+ years. All tumor characteristics, particularly
      T, were worse for colon compared to rectal tumors. Right-sided tumors showed
      worse characteristics for all classifiers but M. The survival analysis on
      patients diagnosed since 2000 showed a hazard ratio of 0.55 for diagnosis before
      age 50 years compared to diagnosis at over 80 years and a modestly better
      prognosis for left-sided compared to right-sided tumors. CONCLUSIONS: The results
      showed systematically more aggressive tumors in young compared to old patients.
      The poorer survival of old patients in colon cancer was not related to the
      available tumor characteristics. However, these partially agreed with the limited
      colonoscopic success with right-sided tumors.

PMID- 21176148
TI  - The majority of total nuclear-encoded non-ribosomal RNA in a human cell is 'dark
      matter' un-annotated RNA.
AB  - BACKGROUND: Discovery that the transcriptional output of the human genome is far
      more complex than predicted by the current set of protein-coding annotations and
      that most RNAs produced do not appear to encode proteins has transformed our
      understanding of genome complexity and suggests new paradigms of genome
      regulation. However, the fraction of all cellular RNA whose function we do not
      understand and the fraction of the genome that is utilized to produce that RNA
      remain controversial. This is not simply a bookkeeping issue because the degree
      to which this un-annotated transcription is present has important implications
      with respect to its biologic function and to the general architecture of genome
      regulation. For example, efforts to elucidate how non-coding RNAs (ncRNAs)
      regulate genome function will be compromised if that class of RNAs is dismissed
      as simply 'transcriptional noise'. RESULTS: We show that the relative mass of RNA
      whose function and/or structure we do not understand (the so called 'dark matter'
      RNAs), as a proportion of all non-ribosomal, non-mitochondrial human RNA (mt
      RNA), can be greater than that of protein-encoding transcripts. This observation
      is obscured in studies that focus only on polyA-selected RNA, a method that
      enriches for protein coding RNAs and at the same time discards the vast majority
      of RNA prior to analysis. We further show the presence of a large number of very
      long, abundantly-transcribed regions (100's of kb) in intergenic space and
      further show that expression of these regions is associated with neoplastic
      transformation. These overlap some regions found previously in normal human
      embryonic tissues and raises an interesting hypothesis as to the function of
      these ncRNAs in both early development and neoplastic transformation.
      CONCLUSIONS: We conclude that 'dark matter' RNA can constitute the majority of
      non-ribosomal, non-mitochondrial-RNA and a significant fraction arises from
      numerous very long, intergenic transcribed regions that could be involved in
      neoplastic transformation.

PMID- 21176149
TI  - SVM classifier to predict genes important for self-renewal and pluripotency of
      mouse embryonic stem cells.
AB  - BACKGROUND: Mouse embryonic stem cells (mESCs) are derived from the inner cell
      mass of a developing blastocyst and can be cultured indefinitely in-vitro. Their
      distinct features are their ability to self-renew and to differentiate to all
      adult cell types. Genes that maintain mESCs self-renewal and pluripotency
      identity are of interest to stem cell biologists. Although significant steps have
      been made toward the identification and characterization of such genes, the list
      is still incomplete and controversial. For example, the overlap among candidate
      self-renewal and pluripotency genes across different RNAi screens is surprisingly
      small. Meanwhile, machine learning approaches have been used to analyze multi
      dimensional experimental data and integrate results from many studies, yet they
      have not been applied to specifically tackle the task of predicting and
      classifying self-renewal and pluripotency gene membership. RESULTS: For this
      study we developed a classifier, a supervised machine learning framework for
      predicting self-renewal and pluripotency mESCs stemness membership genes (MSMG)
      using support vector machines (SVM). The data used to train the classifier was
      derived from mESCs-related studies using mRNA microarrays, measuring gene
      expression in various stages of early differentiation, as well as ChIP-seq
      studies applied to mESCs profiling genome-wide binding of key transcription
      factors, such as Nanog, Oct4, and Sox2, to the regulatory regions of other genes.
      Comparison to other classification methods using the leave-one-out cross
      validation method was employed to evaluate the accuracy and generality of the
      classification. Finally, two sets of candidate genes from genome-wide RNA
      interference screens are used to test the generality and potential application of
      the classifier. CONCLUSIONS: Our results reveal that an SVM approach can be
      useful for prioritizing genes for functional validation experiments and
      complement the analyses of high-throughput profiling experimental data in stem
      cell research.

PMID- 21176150
TI  - Risks from accidental exposures to engineered nanoparticles and neurological
      health effects: a critical review.
AB  - There are certain concerns regarding the safety for the environment and human
      health from the use of engineered nanoparticles (ENPs) which leads to unintended
      exposures, as opposed to the use of ENPs for medical purposes. This review
      focuses on the unintended human exposure of ENPs. In particular, possible effects
      in the brain are discussed and an attempt to assess risks is performed.Animal
      experiments have shown that investigated ENPs (metallic nanoparticles, quantum
      dots, carbon nanotubes) can translocate to the brain from different entry points
      (skin, blood, respiratory pathways). After inhalation or instillation into parts
      of the respiratory tract a very small fraction of the inhaled or instilled ENPs
      reaches the blood and subsequently secondary organs, including the CNS, at a low
      translocation rate. Experimental in vivo and in vitro studies have shown that
      several types of ENPs can have various biological effects in the nervous system.
      Some of these effects could also imply that ENPs can cause hazards, both acutely
      and in the long term. The relevance of these data for risk assessment is far from
      clear. There are at present very few data on exposure of the general public to
      either acute high dose exposure or on chronic exposure to low levels of air-borne
      ENPs. It is furthermore unlikely that acute high dose exposures would occur. The
      risk from such exposures for damaging CNS effects is thus probably very low,
      irrespective of any biological hazard associated with ENPs.The situation is more
      complicated regarding chronic exposures, at low doses. The long term accumulation
      of ENPs can not be excluded. However, we do not have exposure data for the
      general public regarding ENPs. Although translocation to the brain via
      respiratory organs and the circulation appears to be very low, there remains a
      possibility that chronic exposures, and/or biopersistent ENPs, can influence
      processes within the brain that are triggering or aggravating pathological
      processes.In general, the present state of knowledge is unsatisfactory for a
      proper risk assessment in this area. Crucial deficits include lack of exposure
      data, the absence of a proper dose concept, and that studies often fail in
      adequate description of the investigated ENPs.

PMID- 21176151
TI  - Pentoxifylline as an adjunct therapy in children with cerebral malaria.
AB  - BACKGROUND: Pentoxifylline (PTX) affects many processes that may contribute to
      the pathogenesis of severe malaria and it has been shown to reduce the duration
      of coma in children with cerebral malaria. This pilot study was performed to
      assess pharmacokinetics, safety and efficacy of PTX in African children with
      cerebral malaria. METHODS: Ten children admitted to the high dependency unit of
      the Kilifi District Hospital in Kenya with cerebral malaria (Blantyre coma score
      of 2 or less) received quinine plus a continuous infusion of 10 mg/kg/24 hours
      PTX for 72 hours. Five children were recruited as controls and received normal
      saline instead of PTX. Plasma samples were taken for PTX and tumour necrosis
      factor (TNF) levels. Blantyre Coma Score, parasitemia, hematology and vital signs
      were assessed 4 hourly. RESULTS: One child (20%) in the control group died,
      compared to four children (40%) in the PTX group. This difference was not
      significant (p = 0.60). Laboratory parameters and clinical data were comparable
      between groups. TNF levels were lower in children receiving PTX. CONCLUSIONS: The
      small sample size does not permit definitive conclusions, but the mortality rate
      was unexpectedly high in the PTX group.

PMID- 21176152
TI  - Overexpression of proto-oncogene FBI-1 activates membrane type 1-matrix
      metalloproteinase in association with adverse outcome in ovarian cancers.
AB  - BACKGROUND: FBI-1 (factor that binds to the inducer of short transcripts of human
      immunodeficiency virus-1) is a member of the POK (POZ and Kruppel) family of
      transcription factors and play important roles in cellular differentiation and
      oncogenesis. Recent evidence suggests that FBI-1 is expressed at high levels in a
      subset of human lymphomas and some epithelial solid tumors. However, the function
      of FBI-1 in human ovarian cancers remains elusive. RESULTS: In this study, we
      investigated the role of FBI-1 in human ovarian cancers, in particularly, its
      function in cancer cell invasion via modulating membrane type 1-matrix
      metalloproteinase (MT1-MMP). Significantly higher FBI-1 protein and mRNA
      expression levels were demonstrated in ovarian cancers samples and cell lines
      compared with borderline tumors and benign cystadenomas. Increased FBI-1 mRNA
      expression was correlated significantly with gene amplification (P = 0.037).
      Moreover, higher FBI-1 expression was found in metastatic foci (P = 0.036) and
      malignant ascites (P = 0.021), and was significantly associated with advanced
      stage (P = 0.012), shorter overall survival (P = 0.032) and disease-free survival
      (P = 0.016). In vitro, overexpressed FBI-1 significantly enhanced cell migration
      and invasion both in OVCA 420 and SKOV-3 ovarian carcinoma cells, irrespective of
      p53 status, accompanied with elevated expression of MT1-MMP, but not MMP-2 or
      TIMP-2. Moreover, knockdown of MT1-MMP abolished FBI-1-mediated cell migration
      and invasion. Conversely, stable knockdown of FBI-1 remarkably reduced the
      motility of these cells with decreased expression of MT1-MMP. Promoter assay and
      chromatin immunoprecipitation study indicated that FBI-1 could directly interact
      with the promoter spanning ~600 bp of the 5'-flanking sequence of MT1-MMP and
      enhanced its expression in a dose-dependent manner. Furthermore, stable knockdown
      and ectopic expression of FBI-1 decreased and increased cell proliferation
      respectively in OVCA 420, but not in the p53 null SKOV-3 cells. CONCLUSIONS: Our
      results suggested an important role of FBI-1 in ovarian cancer cell
      proliferation, cell mobility, and invasiveness, and that FBI-1 can be a potential
      target of chemotherapy.

PMID- 21176153
TI  - Generation and characterization of high affinity human monoclonal antibodies that
      neutralize staphylococcal enterotoxin B.
AB  - BACKGROUND: Staphylococcal enterotoxins are considered potential biowarfare
      agents that can be spread through ingestion or inhalation. Staphylococcal
      enterotoxin B (SEB) is a widely studied superantigen that can directly stimulate
      T-cells to release a massive amount of proinflammatory cytokines by bridging the
      MHC II molecules on an antigen presenting cell (APC) and the Vbeta chains of the
      T-cell receptor (TCR). This potentially can lead to toxic, debilitating and
      lethal effects. Currently, there are no preventative measures for SEB exposure,
      only supportive therapies. METHODS: To develop a potential therapeutic candidate
      to combat SEB exposure, we have generated three human B-cell hybridomas that
      produce human monoclonal antibodies (HuMAbs) to SEB. These HuMAbs were screened
      for specificity, affinity and the ability to block SEB activity in vitro as well
      as its lethal effect in vivo. RESULTS: The high-affinity HuMAbs, as determined by
      BiaCore analysis, were specific to SEB with minimal crossreactivity to related
      toxins by ELISA. In an immunoblotting experiment, our HuMAbs bound SEB mixed in a
      cell lysate and did not bind any of the lysate proteins. In an in vitro cell
      based assay, these HuMAbs could inhibit SEB-induced secretion of the
      proinflammatory cytokines (INF-gamma and TNF-alpha) by primary human lymphocytes
      with high potency. In an in vivo LPS-potentiated mouse model, our lead antibody,
      HuMAb-154, was capable of neutralizing up to 100 MUg of SEB challenge equivalent
      to 500 times over the reported LD50 (0.2 MUg) , protecting mice from death.
      Extended survival was also observed when HuMAb-154 was administered after SEB
      challenge. CONCLUSION: We have generated high-affinity SEB-specific antibodies
      capable of neutralizing SEB in vitro as well as in vivo in a mouse model. Taken
      together, these results suggest that our antibodies hold the potential as passive
      immunotherapies for both prophylactic and therapeutic countermeasures of SEB
      exposure.

PMID- 21176154
TI  - A single centre experience with sequential and concomitant chemoradiotherapy in
      locally advanced stage IV tonsillar cancer.
AB  - BACKGROUND: Chemo-radiotherapy offers an alternative to primary surgery and
      adjuvant therapy for the management of locally advanced stage IV squamous cell
      carcinomas of the tonsil. METHODS: A retrospective analysis was performed of the
      outcomes of 41 patients with locoregionally advanced squamous cell carcinoma of
      the tonsil treated non-surgically at the Yorkshire Cancer Centre between January
      2004 and December 2005. Due to long radiotherapy waiting times, patients received
      induction chemotherapy with cisplatin and 5-fluorouracil followed by either
      cisplatin concurrent chemoradiotherapy or radiotherapy alone. RESULTS: Median age
      was 55 years (range 34-76 years) and 28 (68%) patients were male. 35/41 patients
      (85%) received 2 or more cycles of induction chemotherapy. Following induction
      chemotherapy, 32/41 patients (78%) had a clinical response. Concomitant
      chemotherapy was given to 30/41 (73%). All patients received the planned
      radiotherapy dose with no delays. There were no treatment related deaths. Six
      (15%) patients had gastrostomy tubes placed before treatment, and 22 (54%)
      required nasogastric tube placement during or after treatment for nutritional
      support. 17 patients required unplanned admissions during treatment for
      supportive care. At 4 months post treatment assessment 35 out of 41 (85%)
      patients achieved complete clinical and radiographic response. Median follow-up
      is 38 months (8-61 months). Local and regional control rate in complete
      responders at 3 years was 91%. Distant metastases have been found in 4 (9.8%)
      patients. Three year progression-free survival rate in all patients is 75%. The 3
      year cause specific survival and overall survival are 75% and 66% respectively.
      CONCLUSION: Cisplatin-based induction and concurrent chemoradiotherapy provides
      excellent tumour control with acceptable toxicity for patients with locally
      advanced tonsillar cancer.

PMID- 21176155
TI  - The impact of mass gatherings and holiday traveling on the course of an influenza
      pandemic: a computational model.
AB  - BACKGROUND: During the 2009 H1N1 influenza pandemic, concerns arose about the
      potential negative effects of mass public gatherings and travel on the course of
      the pandemic. Better understanding the potential effects of temporal changes in
      social mixing patterns could help public officials determine if and when to
      cancel large public gatherings or enforce regional travel restrictions,
      advisories, or surveillance during an epidemic. METHODS: We develop a computer
      simulation model using detailed data from the state of Georgia to explore how
      various changes in social mixing and contact patterns, representing mass
      gatherings and holiday traveling, may affect the course of an influenza pandemic.
      Various scenarios with different combinations of the length of the mass
      gatherings or traveling period (range: 0.5 to 5 days), the proportion of the
      population attending the mass gathering events or on travel (range: 1% to 50%),
      and the initial reproduction numbers R0 (1.3, 1.5, 1.8) are explored. RESULTS:
      Mass gatherings that occur within 10 days before the epidemic peak can result in
      as high as a 10% relative increase in the peak prevalence and the total attack
      rate, and may have even worse impacts on local communities and travelers'
      families. Holiday traveling can lead to a second epidemic peak under certain
      scenarios. Conversely, mass traveling or gatherings may have little effect when
      occurring much earlier or later than the epidemic peak, e.g., more than 40 days
      earlier or 20 days later than the peak when the initial R0 = 1.5. CONCLUSIONS:
      Our results suggest that monitoring, postponing, or cancelling large public
      gatherings may be warranted close to the epidemic peak but not earlier or later
      during the epidemic. Influenza activity should also be closely monitored for a
      potential second peak if holiday traveling occurs when prevalence is high.

PMID- 21176156
TI  - Genomic regions associated with kyphosis in swine.
AB  - BACKGROUND: A back curvature defect similar to kyphosis in humans has been
      observed in swine herds. The defect ranges from mild to severe curvature of the
      thoracic vertebrate in split carcasses and has an estimated heritability of 0.3.
      The objective of this study was to identify genomic regions that affect this
      trait. RESULTS: Single nucleotide polymorphism (SNP) associations performed with
      198 SNPs and microsatellite markers in a Duroc-Landrace-Yorkshire resource
      population (U.S. Meat Animal Research Center, USMARC resource population) of
      swine provided regions of association with this trait on 15 chromosomes.
      Positional candidate genes, especially those involved in human skeletal
      development pathways, were selected for SNP identification. SNPs in 16 candidate
      genes were genotyped in an F2 population (n = 371) and the USMARC resource herd
      (n = 1,257) with kyphosis scores. SNPs in KCNN2 on SSC2, RYR1 and PLOD1 on SSC6
      and MYST4 on SSC14 were significantly associated with kyphosis in the resource
      population of swine (P <= 0.05). SNPs in CER1 and CDH7 on SSC1, PSMA5 on SSC4,
      HOXC6 and HOXC8 on SSC5, ADAMTS18 on SSC6 and SOX9 on SSC12 were significantly
      associated with the kyphosis trait in the F2 population of swine (P <= 0.05).
      CONCLUSIONS: These data suggest that this kyphosis trait may be affected by
      several loci and that these may differ by population. Carcass value could be
      improved by effectively removing this undesirable trait from pig populations.

PMID- 21176157
TI  - Where there is no evidence: use of expert consensus methods to fill the evidence
      gap in low-income countries and cultural minorities.
AB  - BACKGROUND: In both developing countries and in relation to cultural minorities
      there have been calls to scale up mental health services and for evidence
      informed policy and practice. EVIDENCE BASED MEDICINE: The evidence based
      medicine movement has had a major influence in improving practice. However,
      implementation of this approach has some major difficulties. One that has been
      neglected is the situation where there is no relevant evidence. This situation is
      more likely to occur for healthcare decisions in developing countries or for
      cultural minorities within developed countries, because resources do not exist
      for expensive research studies. CONSENSUS METHODS: Consensus methods, such as the
      Delphi process, can be useful in providing an evidence base in situations where
      there is insufficient evidence. They provide a way of systematically tapping the
      expertise of people working in the area and give evidence that is readily
      applicable for a particular country and culture. Although consensus methods are
      often thought of as low in the hierarchy of evidence, consensus is central to the
      scientific process. We present four examples where the Delphi method was used to
      assess expert consensus in situations where no other evidence existed: estimating
      the prevalence of dementia in developing countries, developing mental health
      first aid guidelines in Asian countries, mental health first aid guidelines for
      Australian Aboriginal people, and modification of the concept of 'recovery' for
      Australian immigrant communities. CONCLUSION: Consensus methods can provide a
      basis for decision-making and considered action when there is no evidence or when
      there are doubts about the applicability of evidence that has been generated from
      other populations or health system settings.

PMID- 21176158
TI  - Cost-effectiveness of six strategies for Helicobacter pylori diagnosis and
      management in uninvestigated dyspepsia assuming a high resource intensity
      practice pattern.
AB  - BACKGROUND: Initial assessment of dyspepsia often includes noninvasive testing
      for Helicobacter pylori infection. Commercially available tests vary widely in
      cost and accuracy. Although there is extensive literature on the cost
      effectiveness of H. pylori treatment, there is little information comparing the
      cost-effectiveness of various currently used, noninvasive testing strategies.
      METHODS: A Markov simulation was used to calculate cost per symptom-free year and
      cost per correct diagnosis. Uncertainty in outcomes was estimated using
      probabilistic sensitivity analysis. RESULTS: Under the baseline assumptions, cost
      per symptom-free year was $122 for empiric proton pump inhibitor (PPI) trial, and
      costs for the noninvasive test strategies ranged from $123 (stool antigen) to
      $129 (IgG/IgA combined serology). Confidence intervals had significant overlap.
      CONCLUSIONS: Under our assumptions for how testing for H. pylori infection is
      employed in United States medical practice, the available noninvasive tests all
      have similar cost-effectiveness between one another as well as with empiric PPI
      trial.

PMID- 21176159
TI  - Antimicrobial activity of spherical silver nanoparticles prepared using a
      biocompatible macromolecular capping agent: evidence for induction of a greatly
      prolonged bacterial lag phase.
AB  - BACKGROUND: We have evaluated the antimicrobial properties of Ag-based
      nanoparticles (Nps) using two solid phase bioassays and found that 10-20 MUL of
      0.3-3 MUM keratin-stabilized Nps (depending on the starting bacterial
      concentration = CI) completely inhibited the growth of an equivalent volume of
      ca. 103 to 104 colony forming units per mL (CFU mL-1) Staphylococcus aureus,
      Salmonella Typhimurium, or Escherichia coli O157:H7 on solid surfaces. Even after
      one week at 37 degrees C on solid media, no growth was observed. At lower Np
      concentrations (= [Np]s), visible colonies were observed but they eventually
      ceased growing. RESULTS: To further study the physiology of this growth
      inhibition, we repeated these experiments in liquid phase by observing microbial
      growth via optical density at 590 nm (OD) at 37 degrees C in the presence of a
      [Np] = 0 to 10-6 M. To extract various growth parameters we fit all OD[t] data to
      a common sigmoidal function which provides measures of the beginning and final OD
      values, a first-order rate constant (k), as well as the time to calculated 1/2
      maximal OD (tm) which is a function of CI, k, as well as the microbiological lag
      time (T).Performing such experiments using a 96-well microtitre plate reader, we
      found that growth always occurred in solution but tm varied between 7 (controls;
      CI = 8 * 103 CFU mL-1) and > 20 hrs using either the citrate-([Np] ~ 3 * 10-7 M)
      or keratin-based ([Np] ~ 10-6 M) Nps and observed that {?tm/? [Np]}citrate ~ 5 *
      107 and {?tm/? [Np]}keratin ~ 107 hr.L mol-1. We also found that there was little
      effect of Nps on S. aureus growth rates which varied only between k = 1.0 and 1.2
      hr-1 (1.1 +/- 0.075 hr-1). To test the idea that the Nps were changing the
      initial concentration (CI) of bacteria (i.e., cell death), we performed
      probabilistic calculations assuming that the perturbations in tm were due to CI
      alone. We found that such large perturbations in tm could only come about at a CI
      where the probability of any growth at all was small. This result indicates that
      much of the Np-induced change in tm was due to a greatly increased T (e.g., from
      ca. 1 to 15-20 hrs). For the solid phase assays we hypothesize that the bacteria
      eventually became non-culturable since they were inhibited from undergoing
      further cell division (T > many days). CONCLUSION: We propose that the difference
      between the solid and liquid system relates to the obvious difference in the
      exposure, or residence, time of the Nps with respect to the bacterial cell
      membrane inasmuch as when small, Np-inhibited colonies were selected and streaked
      on fresh (i.e., no Nps present) media, growth proceeded normally: e.g., a small,
      growth-inhibited colony resulted in a plateful of typical S. aureus colonies when
      streaked on fresh, solid media.

PMID- 21176160
TI  - Immune restoration disease and changes in CD4+ T-cell count in HIV- infected
      patients during highly active antiretroviral therapy at Zewditu memorial
      hospital, Addis Ababa, Ethiopia.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) improves the immune
      function and decreases morbidity, mortality and opportunistic infections (OIs) in
      HIV-infected patients. However, since the use of HAART, immune restoration
      disease (IRD) has been described in association with many OIs. Our objective was
      to determine the proportion of IRD, changes in CD4+ T-cell count and possible
      risk factors of IRD in HIV-infected patients. METHODS: A retrospective study of
      all HIV- infected patients starting HAART between September 1, 2005 and August
      31, 2006 at Zewditu memorial hospital HIV clinic, Addis Ababa, Ethiopia was
      conducted. All laboratory and clinical data were extracted from computerized
      clinic records and patient charts. RESULTS: A total of 1166 HIV- infected
      patients with mean +/- SD age of 36 +/- 9.3 years were on HAART. IRD was
      identified in 170 (14.6%) patients. OIs diagnosed in the IRD patients were
      tuberculosis (66.5%, 113/170), toxoplasmosis (12.9%, 22/170), herpes zoster rash
      (12.9%, 22/170), Pneumocystis jirovecii pneumonia (4.1%, 7/170), and
      cryptococcosis (3.5%, 6/170). Of the 170 patients with IRD, 124 (72.9%) patients
      developed IRD within the first 3 months of HAART initiation. Low baseline CD4+ T
      cell count (odds ratio [OR], 3.16, 95% confidence interval [CI], 2.19-4.58) and
      baseline extra pulmonary tuberculosis (OR, 7.7, 95% CI, 3.36-17.65) were
      associated with development of IRD. Twenty nine (17.1%) of the IRD patients
      needed to use systemic anti-inflammatory treatment where as 19(11.2%) patients
      required hospitalization associated to the IRD occurrence. There was a total of 8
      (4.7%) deaths attributable to IRD. CONCLUSIONS: The proportion and risk factors
      of IRD and the pattern of OIs mirrored reports from other countries. Close
      monitoring of patients during the first three months of HAART initiation is
      important to minimize clinical deterioration related to IRD.

PMID- 21176161
TI  - Hydrogen peroxide induced genomic instability in nucleotide excision repair
      deficient lymphoblastoid cells.
AB  - BACKGROUND: The Nucleotide Excision Repair (NER) pathway specialises in UV
      induced DNA damage repair. Inherited defects in the NER can predispose
      individuals to Xeroderma Pigmentosum (XP). UV-induced DNA damage cannot account
      for the manifestation of XP in organ systems not directly exposed to sunlight.
      While the NER has recently been implicated in the repair of oxidative DNA
      lesions, it is not well characterised. Therefore we sought to investigate the
      role of NER factors Xeroderma Pigmentosum A (XPA), XPB and XPD in oxidative DNA
      damage-repair by subjecting lymphoblastoid cells from patients suffering from XP
      A, XP-D and XP-B with Cockayne Syndrome to hydrogen peroxide (H2O2). RESULTS:
      Loss of functional XPB or XPD but not XPA led to enhanced sensitivity towards
      H2O2-induced cell death. XP-deficient lymphoblastoid cells exhibited increased
      susceptibility to H2O2-induced DNA damage with XPD showing the highest
      susceptibility and lowest repair capacity. Furthermore, XPB- and XPD-deficient
      lymphoblastoid cells displayed enhanced DNA damage at the telomeres. XPA- and XPB
      deficient lymphoblastoid cells also showed differential regulation of XPD
      following H2O2 treatment. CONCLUSIONS: Taken together, our data implicate a role
      for the NER in H2O2-induced oxidative stress management and further corroborates
      that oxidative stress is a significant contributing factor in XP symptoms.
      Resistance of XPA-deficient lymphoblastoid cells to H2O2-induced cell death while
      harbouring DNA damage poses a potential cancer risk factor for XPA patients. Our
      data implicate XPB and XPD in the protection against oxidative stress-induced DNA
      damage and telomere shortening, and thus premature senescence.

PMID- 21176162
TI  - A wide spectrum of clinical and brain MRI findings in patients with SLC19A3
      mutations.
AB  - BACKGROUND: SLC19A3 (solute carrier family 19, member 3) is a thiamin transporter
      with 12 transmembrane domains. Homozygous or compound heterozygous mutations in
      SLC19A3 cause two distinct clinical phenotypes, biotin-responsive basal ganglia
      disease and Wernicke's-like encephalopathy. Biotin and/or thiamin are effective
      therapies for both diseases. METHODS: We conducted on the detailed clinical,
      brain MRI and molecular genetic analysis of four Japanese patients in a Japanese
      pedigree who presented with epileptic spasms in early infancy, severe psychomotor
      retardation, and characteristic brain MRI findings of progressive brain atrophy
      and bilateral thalami and basal ganglia lesions. RESULTS: Genome-wide linkage
      analysis revealed a disease locus at chromosome 2q35-37, which enabled
      identification of the causative mutation in the gene SLC19A3. A pathogenic
      homozygous mutation (c.958G > C, [p.E320Q]) in SLC19A3 was identified in all four
      patients and their parents were heterozygous for the mutation. Administration of
      a high dose of biotin for one year improved neither the neurological symptoms nor
      the brain MRI findings in one patient. CONCLUSION: Our cases broaden the
      phenotypic spectrum of disorders associated with SLC19A3 mutations and highlight
      the potential benefit of biotin and/or thiamin treatments and the need to assess
      the clinical efficacy of these treatments.

PMID- 21176163
TI  - Whole genome sequencing of Saccharomyces cerevisiae: from genotype to phenotype
      for improved metabolic engineering applications.
AB  - BACKGROUND: The need for rapid and efficient microbial cell factory design and
      construction are possible through the enabling technology, metabolic engineering,
      which is now being facilitated by systems biology approaches. Metabolic
      engineering is often complimented by directed evolution, where selective pressure
      is applied to a partially genetically engineered strain to confer a desirable
      phenotype. The exact genetic modification or resulting genotype that leads to the
      improved phenotype is often not identified or understood to enable further
      metabolic engineering. RESULTS: In this work we performed whole genome high
      throughput sequencing and annotation can be used to identify single nucleotide
      polymorphisms (SNPs) between Saccharomyces cerevisiae strains S288c and CEN.PK113
      7D. The yeast strain S288c was the first eukaryote sequenced, serving as the
      reference genome for the Saccharomyces Genome Database, while CEN.PK113-7D is a
      preferred laboratory strain for industrial biotechnology research. A total of
      13,787 high-quality SNPs were detected between both strains (reference strain:
      S288c). Considering only metabolic genes (782 of 5,596 annotated genes), a total
      of 219 metabolism specific SNPs are distributed across 158 metabolic genes, with
      85 of the SNPs being nonsynonymous (e.g., encoding amino acid modifications).
      Amongst metabolic SNPs detected, there was pathway enrichment in the galactose
      uptake pathway (GAL1, GAL10) and ergosterol biosynthetic pathway (ERG8, ERG9).
      Physiological characterization confirmed a strong deficiency in galactose uptake
      and metabolism in S288c compared to CEN.PK113-7D, and similarly, ergosterol
      content in CEN.PK113-7D was significantly higher in both glucose and galactose
      supplemented cultivations compared to S288c. Furthermore, DNA microarray
      profiling of S288c and CEN.PK113-7D in both glucose and galactose batch cultures
      did not provide a clear hypothesis for major phenotypes observed, suggesting that
      genotype to phenotype correlations are manifested post-transcriptionally or post
      translationally either through protein concentration and/or function.
      CONCLUSIONS: With an intensifying need for microbial cell factories that produce
      a wide array of target compounds, whole genome high-throughput sequencing and
      annotation for SNP detection can aid in better reducing and defining the
      metabolic landscape. This work demonstrates direct correlations between genotype
      and phenotype that provides clear and high-probability of success metabolic
      engineering targets. The genome sequence, annotation, and a SNP viewer of
      CEN.PK113-7D are deposited at http://www.sysbio.se/cenpk.

PMID- 21176164
TI  - Protective effect of the daming capsule on impaired baroreflexes in STZ-induced
      diabetic rats with hyperlipoidemia.
AB  - BACKGROUND: The Daming capsule (DMC) is a traditional Chinese medicine used to
      treat hyperlipoidemia. Both clinic trials and studies on animal models have
      demonstrated that DMC is beneficial against diabetic symptoms. Impairment of the
      baroreflex can cause life-threatening arrhythmias and sudden cardiac death in
      patients with diabetes mellitus (DM). This study was designed to elucidate the
      effects of DMC on baroreflexes in streptozocin (STZ)-induced diabetic rats with
      hyperlipoidemia. METHODS: Wistar rats were randomly divided into three groups:
      untreated controls, rats pretreated STZ and high lipids (a diabetes model or DM
      rats), and DM rats treated with DMC. The baroreflex sensitivity was examined
      during intravenous injection of phenylephrine (PE) or sodium nitroprusside (SNP)
      and quantified by the change in heart rate over the change in mean arterial blood
      pressure (DeltaHR/DeltaMABP). Morphological remodeling of baroreceptors was
      analyzed by transmission electron microscopy (TEM). The mRNA levels and
      expression of GluR2 and a GABAA receptor subunit were measured by quantitative RT
      PCR and Western blotting. RESULTS: Compared to untreated DM rats, DMC
      significantly elevated the ratio of DeltaHR/DeltaMABP by enhancing the
      compensatory reduction in HR (-DeltaHR) in response to PE-induced hypertension
      (+DeltaMABP) (P < 0.05). In the presence of SNP, DMC increased the DeltaMABP (P <
      0.05). In addition, DMC markedly shortened the duration of blood pressure changes
      elicited by PE or SNP in DM rats compared to the untreated DM group (P < 0.05).
      Electron microscopy revealed disrupted myelin sheaths, swollen ER, and lysed
      mitochondria in the nucleus ambiguous (NAm) DM rats. These signs of
      neuropathology were largely prevented by treatment with DMC for 30 days.
      Treatment with DMC elevated both mRNA and protein level of GluR2 in the NAm of DM
      rats, but had no effect on GABAA receptor expression. CONCLUSION: The Daming
      capsule partially reversed the parasympathetic baroreflex impairment observed in
      STZ-induced diabetic rats with hyperlipoidemia. Treatment with DMC also prevented
      the degeneration of neurons and myelinated axons in the brain stem NAm and
      reversed the down-regulation of GluR2 mRNA. Rescue of NAm function may contribute
      to the medicinal properties of DMC in diabetic rats.

PMID- 21176165
TI  - Impact of home and community-based services on hospitalisation and
      institutionalisation among individuals eligible for long-term care insurance in
      Japan.
AB  - BACKGROUND: This population-based retrospective cohort study aimed to clarify the
      impact of home and community-based services on the hospitalisation and
      institutionalisation of individuals certified as eligible for long-term care
      insurance (LTCI) benefits. METHODS: Health insurance data and LTCI data were
      combined into a database of 1,020 individuals in two farming communities in
      Hokkaido who were enrolled in Citizen's Health Insurance. They had not received
      long-term care services prior to April 1, 2000 and were newly certified as
      eligible for Long-Term Care Insurance benefits between April 1, 2000 and February
      29, 2008. The analysis covered 565 subjects who had not been hospitalised or
      institutionalised at the time of first certification of LTCI benefits. The
      adjusted hazard ratios (HRs) of hospitalisation or institutionalisation or death
      after the initial certification were calculated using the Cox proportional hazard
      model. The predictors were age, sex, eligibility level, area of residence,
      income, year of initial certification and average monthly outpatient medical
      expenditures, in addition to average monthly total home and community-based
      services expenditures (analysis 1), the use or no use of each type of service
      (analysis 2), and average monthly expenditures for home-visit and day-care types
      of services, the use or no use of respite care, and the use or no use of rental
      services for assistive devices (analysis 3). RESULTS: Users of home and community
      based services were less likely than non-users to be hospitalised or
      institutionalised. Among the types of services, users of respite care (HR: 0.71,
      95% confidence interval [CI]: 0.55-0.93) and rental services for assistive
      devices (HR: 0.70, 95% CI: 0.54-0.92) were less likely to be hospitalised or
      institutionalised than non-users. For those with relatively light needs, users of
      day care were also less likely to be hospitalised or institutionalized than non
      users (HR: 0.77, 95% CI: 0.61-0.98). CONCLUSIONS: Respite care, rental services
      for assistive devices and day care are effective in preventing hospitalisation
      and institutionalisation. Our results suggest that home and community-based
      services contribute to the goal of the LTCI system of encouraging individuals
      certified as needing long-term care to live independently at home for as long as
      possible.

PMID- 21176166
TI  - The reliability of toe systolic pressure and the toe brachial index in patients
      with diabetes.
AB  - BACKGROUND: The Ankle Brachial Index is a useful clinical test for establishing
      blood supply to the foot. However, there are limitations to this method when
      conducted on people with diabetes. As an alternative to the Ankle Brachial Index,
      measuring Toe Systolic Pressures and the Toe Brachial Index have been recommended
      to assess the arterial blood supply to the foot. This study aimed to determine
      the intra and inter-rater reliability of the measurement of Toe Systolic Pressure
      and the Toe Brachial Index in patients with diabetes using a manual measurement
      system. METHODS: This was a repeated measures, reliability study. Three raters
      measured Toe Systolic Pressure and the Toe Brachial Index in thirty participants
      with diabetes. Measurement sessions occurred on two occasions, one week apart,
      using a manual photoplethysmography unit (Hadeco Smartdop 45) and a standardised
      measurement protocol. RESULTS: The mean intra-class correlation for intra-rater
      reliability for toe systolic pressures was 0.87 (95% LOA: -25.97 to 26.06 mmHg)
      and the mean intra-class correlation for Toe Brachial Indices was 0.75 (95% LOA: 
      0.22 to 0.28). The intra-class correlation for inter-rater reliability was 0.88
      for toe systolic pressures (95% LOA: -22.91 to 29.17.mmHg) and 0.77 for Toe
      Brachial Indices (95% LOA: -0.21 to 0.22). CONCLUSION: Despite the reasonable
      intra-class correlation results, the range of error (95% LOA) was broad. This
      raises questions regarding the reliability of using a manual sphygmomanometer and
      PPG for the Toe Systolic Pressure and Toe Brachial Indice.

PMID- 21176167
TI  - Human TGFalpha-derived peptide TGFalphaL3 fused with superantigen for
      immunotherapy of EGFR-expressing tumours.
AB  - BACKGROUND: Monoclonal antibodies have been employed as targeting molecules of
      superantigen for the preclinical treatment of a variety of tumours. However,
      other targeting molecules, such as tumour-related ligands or peptides, are less
      exploited. Here, we tested other targeting molecules by genetically fusing the
      third loop of transforming growth factor alpha (TGFalphaL3) to mutant
      staphylococcal enterotoxin A (SEAD227A). RESULTS: The resultant fusion proteins
      were expressed in E. coli and purified to homogeneity through a Ni-NTA affinity
      column. Fusion protein TGFalphaL3SEAD227A can promote splenocyte proliferation to
      a level comparable to recombinant SEA (rSEA) and bind to EGFR-expressing tumour
      cells in an EGFR-dependent way. Consistent with these observations,
      TGFalphaL3SEAD227A exerted an inhibitory effect on the growth of EGFR-expressing
      tumour cells both in vitro and in vivo. Notably, significant infiltrations of
      CD8+ and CD4+ T cells were detected in the tumour tissues of these C57BL/6 mice
      treated with TGFalphaL3SEAD227A, suggesting the involvement of T cells in this
      tumour-inhibitory process. CONCLUSIONS: The data here showed that TGFalphaL3 is
      capable of targeting superantigen to tumours and exerting an inhibitory effect on
      tumour growth, which enables TGFalphaL3SEAD227A to be an attractive candidate for
      the immunotherapy of EGFR-expressing tumours.

PMID- 21176168
TI  - PARP-1 cleavage fragments: signatures of cell-death proteases in
      neurodegeneration.
AB  - The normal function of poly (ADP-ribose) polymerase-1 (PARP-1) is the routine
      repair of DNA damage by adding poly (ADP ribose) polymers in response to a
      variety of cellular stresses. Recently, it has become widely appreciated that
      PARP-1 also participates in diverse physiological and pathological functions from
      cell survival to several forms of cell death and has been implicated in gene
      transcription, immune responses, inflammation, learning, memory, synaptic
      functions, angiogenesis and aging. In the CNS, PARP inhibition attenuates injury
      in pathologies like cerebral ischemia, trauma and excitotoxicity demonstrating a
      central role of PARP-1 in these pathologies. PARP-1 is also a preferred substrate
      for several 'suicidal' proteases and the proteolytic action of suicidal proteases
      (caspases, calpains, cathepsins, granzymes and matrix metalloproteinases (MMPs))
      on PARP-1 produces several specific proteolytic cleavage fragments with different
      molecular weights. These PARP-1 signature fragments are recognized biomarkers for
      specific patterns of protease activity in unique cell death programs. This review
      focuses on specific suicidal proteases active towards PARP-1 to generate
      signature PARP-1 fragments that can identify key proteases and particular forms
      of cell death involved in pathophysiology. The roles played by some of the PARP-1
      fragments and their associated binding partners in the control of different forms
      of cell death are also discussed.

PMID- 21176170
TI  - The impact of hyperbaric oxygen therapy on serological values of vascular
      endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).
AB  - BACKGROUND: Hyperbaric oxygen (HBO) therapy is an effective adjunct treatment for
      ischemic disorders such as chronic infection or chronic wounds. It combines
      hyperoxic effects with the stimulating potential of post-therapeutic reactive
      hypoxia. As its crucial effects, stimulation of fibroblast growth, induction of
      collagen synthesis and the initiation of angiogenesis are discussed. Angiogenesis
      is a multistage process resulting in the growth of blood vessels. It includes
      degradation of extracellular matrix, proliferation and migration of different
      cell populations and finally formation of new vessel structures. This complex
      chain of procedures is orchestrated by different cytokines and growth factors.
      Crucial mediators of angiogenesis are basic fibroblast growth factor (bFGF) and
      vascular endothelial growth factor (VEGF); their in-vivo function is still not
      fully understood. METHODS: Forty-three patients suffering from sudden
      sensorineural hearing loss or tinnitus were treated with HBO. The therapy
      included 10 sessions of 90 minutes each, one session a day. Serological levels of
      bFGF and VEGF were assessed by enzyme-linked immunosorbent assays performed
      according to the manufacturer's instructions on day 1, 2, 5 and 10 of HBO therapy
      and were compared to mean values of the control group, related to the patient's
      age and sex, and their development observed over the ten days of HBO. RESULTS:
      There was no sex- or age dependency of bFGF observed in the present study,
      whereas under HBO our results showed a significant mitigation of the bFGF
      concentration. In the present data, there was no connection between the VEGF
      concentration and the patients' ages. Women showed significantly higher levels of
      VEGF. There was no significant change of VEGF concentration or the VEGF/bFGF
      ratio during HBO. All scored results varied within the range of standard values
      as described in the current literature. CONCLUSIONS: A significant effect of HBO
      on serum concentrations of bFGF and VEGF was not verified in the present study.
      Additional application of exogenous growth factors in conjunction with HBO was
      not obviously linked by a coherent cause-and-effect chain as far as wound healing
      is concerned.

PMID- 21176169
TI  - Association of the rs738409 polymorphism in PNPLA3 with liver damage and the
      development of nonalcoholic fatty liver disease.
AB  - BACKGROUND: In a genome-wide association scan, the single-nucleotide polymorphism
      (SNP) rs738409 in the patatin-like phospholipase 3 gene (PNPLA3) was strongly
      associated with increased liver fat content. We investigated whether this SNP is
      associated with the occurrence and progression of nonalcoholic fatty liver
      disease (NAFLD) in the Japanese population. METHODS: SNP rs738409 was genotyped
      by the Taqman assay in 253 patients with NAFLD (189 with nonalcoholic
      steatohepatitis [NASH] and 64 with simple steatosis) and 578 control subjects.
      All patients with NAFLD underwent liver biopsy. Control subjects had no metabolic
      disorders. For a case-control study, the chi(2)-test (additive model) was
      performed. Odds ratios (ORs) were adjusted for age, gender, and body mass index
      (BMI) by using multiple logistic regression analysis with genotypes (additive
      model), age, gender, and BMI as the independent variables. Multiple linear
      regression analysis was performed to test the independent effect of risk allele
      on clinical parameters while considering the effects of other variables (age,
      gender, and BMI), which were assumed to be independent of the effect of the SNP.
      RESULTS: The risk allele (G-allele) frequency of rs738409 was 0.44 in the control
      subjects and 0.60 in patients with NAFLD; this shows a strong association with
      NAFLD (additive model, P = 9.4 x 10(-10)). The OR (95% confidence interval)
      adjusted for age, gender, and BMI was 1.73 (1.25-2.38). Multiple linear
      regression analysis indicated that the G-allele of rs738409 was significantly
      associated with increases in aspartate transaminase (AST) (P = 0.00013), alanine
      transaminase (ALT) (P = 9.1 x 10(-6)), and ferritin levels (P = 0.014), and the
      fibrosis stage (P = 0.011) in the patients with NAFLD, even after adjustment for
      age, gender, and BMI. The steatosis grade was not associated with rs738409.
      CONCLUSIONS: We found that in the Japanese population, individuals harboring the
      G-allele of rs738409 were susceptible to NAFLD, and that rs738409 was associated
      with plasma levels of ALT, AST, and ferritin, and the histological fibrosis
      stage. Our study suggests that PNPLA3 may be involved in the progression of
      fibrosis in NAFLD.

PMID- 21176171
TI  - Data linkage: a powerful research tool with potential problems.
AB  - BACKGROUND: Policy makers, clinicians and researchers are demonstrating
      increasing interest in using data linked from multiple sources to support
      measurement of clinical performance and patient health outcomes. However, the
      utility of data linkage may be compromised by sub-optimal or incomplete linkage,
      leading to systematic bias. In this study, we synthesize the evidence identifying
      participant or population characteristics that can influence the validity and
      completeness of data linkage and may be associated with systematic bias in
      reported outcomes. METHODS: A narrative review, using structured search methods
      was undertaken. Key words "data linkage" and Mesh term "medical record linkage"
      were applied to Medline, EMBASE and CINAHL databases between 1991 and 2007.
      Abstract inclusion criteria were; the article attempted an empirical evaluation
      of methodological issues relating to data linkage and reported on patient
      characteristics, the study design included analysis of matched versus unmatched
      records, and the report was in English. Included articles were grouped
      thematically according to patient characteristics that were compared between
      matched and unmatched records. RESULTS: The search identified 1810 articles of
      which 33 (1.8%) met inclusion criteria. There was marked heterogeneity in study
      methods and factors investigated. Characteristics that were unevenly distributed
      among matched and unmatched records were; age (72% of studies), sex (50% of
      studies), race (64% of studies), geographical/hospital site (93% of studies),
      socio-economic status (82% of studies) and health status (72% of studies).
      CONCLUSION: A number of relevant patient or population factors may be associated
      with incomplete data linkage resulting in systematic bias in reported clinical
      outcomes. Readers should consider these factors in interpreting the reported
      results of data linkage studies.

PMID- 21176173
TI  - Beta 2 antagonism in acute respiratory failure.
AB  - Post hoc analyses from the B-type natriuretic peptide for Acute Shortness of
      Breath Evaluation (BASEL)-II-ICU study suggest an association between beta
      blocker usage at admission and improved mortality in patients treated in the
      intensive care unit for acute respiratory failure. Although this evidence is
      encouraging, there is a need for a phase 2 proof-of-concept randomized controlled
      trial of beta-blocker therapy in patients admitted with acute respiratory
      failure.

PMID- 21176172
TI  - The neurobiological basis of ADHD.
AB  - Attention-Deficit/Hyperactivity Disorder is not a single pathophysiological
      entity and appears to have a complex etiology. There are multiple genetic and
      environmental risk factors with small individual effect that act in concert to
      create a spectrum of neurobiological liability. Structural imaging studies show
      that brains of children with Attention-Deficit/Hyperactivity Disorder are
      significantly smaller than unaffected controls. The prefrontal cortex, basal
      ganglia and cerebellum are differentially affected and evidence indicating
      reduced connectivity in white matter tracts in key brain areas is emerging.
      Genetic, pharmacological, imaging, and animal models highlight the important role
      of dopamine dysregulation in the neurobiology of Attention-Deficit/Hyperactivity
      Disorder. To date, stimulants are the most effective psychopharmacological
      treatments available for Attention-Deficit/Hyperactivity Disorder. Currently only
      immediate release methylphenidate and atomoxetine are approved for the treatment
      of ADHD in Italy. Drug treatment should always be part of a comprehensive plan
      that includes psychosocial, behavioural and educational advice and interventions.

PMID- 21176174
TI  - Additional bad news from regulatory T cells in sepsis.

PMID- 21176175
TI  - Breast cancer metastasis to the bone: mechanisms of bone loss.
AB  - Breast cancer frequently metastasizes to the skeleton, interrupting the normal
      bone remodeling process and causing bone degradation. Osteolytic lesions are the
      end result of osteoclast activity; however, osteoclast differentiation and
      activation are mediated by osteoblast production of RANKL (receptor activator for
      NFkappaB ligand) and several osteoclastogenic cytokines. Osteoblasts themselves
      are negatively affected by cancer cells as evidenced by an increase in apoptosis
      and a decrease in proteins required for new bone formation. Thus, bone loss is
      due to both increased activation of osteoclasts and suppression of osteoblasts.
      This review summarizes the current understanding of the osteolytic mechanisms of
      bone metastases, including a discussion of current therapies.

PMID- 21176177
TI  - Anemia in the ICU: are your patients needin' erythropoetin?

PMID- 21176176
TI  - Anti-tumour activity of bisphosphonates in preclinical models of breast cancer.
AB  - There is increasing evidence of anti-tumour effects of bisphosphonates from pre
      clinical studies, supporting a role for these drugs beyond their traditional use
      in treatment of cancer-induced bone disease. A range of model systems have been
      used to investigate the effects of different bisphosphonates on tumour growth,
      both in bone and at peripheral sites. Most of these studies conclude that
      bisphosphonates cause a reduction in tumour burden, but that early intervention
      and the use of high and/or repeated dosing is required. Successful eradication of
      cancer may only be achievable by targeting the tumour cells directly whilst also
      modifying the tumour microenvironment. In line with this, bisphosphonates are
      demonstrated to be particularly effective at reducing breast tumour growth when
      used in combination with agents that directly target cancer cells. Recent studies
      have shown that the effects of bisphosphonates on breast tumours are not limited
      to bone, and that prolonged anti-tumour effects may be achieved following their
      inclusion in combination therapy. This has opened the field to a new strand of
      bisphosphonate research, focussed on elucidating their effects on cells and
      components of the local, regional and distal tumour microenvironment. This review
      highlights the recent developments in relation to proposed anti-tumour effects of
      bisphosphonates reported from in vitro and in vivo models, and summarises the
      data from key breast cancer studies. Evidence for effects on different processes
      and cell types involved in cancer development and progression is discussed, and
      the main outstanding issues identified.

PMID- 21176178
TI  - Does consuming isoflavones reduce or increase breast cancer risk?
AB  - Epidemiological studies suggest that consumption of phytoestrogens, in particular
      isoflavones, correlates with a lower incidence of breast cancer. However, data
      from human intervention studies have been less clear. Several meta-analyses have
      reported beneficial but relatively weak effects of isoflavone consumption on
      reduction of hot flushes and osteoporosis and improvement of cholesterol levels.
      However, the effects of isoflavones on early breast cancer markers differ between
      pre- and post-menopausal women. Conclusions on whether exposure of animals (mice
      and rats) to isoflavones protects against or promotes breast cancer development
      and growth vary between different studies. These results, taken together with the
      heterogeneous outcomes of human interventions, have led to a controversy
      surrounding the intake of isoflavone to reduce breast cancer risk. Here, we
      describe the results of recent human and animal intervention studies and discuss
      factors that might explain the variation in results. We also describe possible
      molecular mechanisms of action of isoflavones; distinguishing which mechanism(s)
      are involved is needed if we are to solve the controversy surrounding the actions
      of these compounds.

PMID- 21176180
TI  - Pre-analytic variables and phospho-specific antibodies: the Achilles heel of
      immunohistochemistry.
AB  - Immunohistochemistry is the most common method for companion diagnostic testing
      in breast cancer. The readings for estrogen receptor, progesterone receptor, and
      Her2 directly affect prescription of critical therapies. However,
      immunohistochemistry is highly sensitive to innumerable pre-analytic variables
      that result in loss of signal in these assays. Perhaps the most significant pre
      analytic variable is cold ischemic time. The work of Pinhel and colleagues in the
      previous issue of Breast Cancer Research examines the effects of cold ischemic
      time and finds a chilling result. The authors show that while the classic markers
      may be only mildly affected, phospho-specific markers are highly sensitive to
      this artifact. As a result, it is likely that future companion diagnostic tests
      that include phospho-specific epitopes will be reliably done only in core needle
      biopsies that minimize ischemic time.

PMID- 21176179
TI  - From RNA-seq reads to differential expression results.
AB  - Many methods and tools are available for preprocessing high-throughput RNA
      sequencing data and detecting differential expression.

PMID- 21176181
TI  - Time-dependent mRNA expression of selected pro-inflammatory factors in the
      endometrium of primiparous cows postpartum.
AB  - BACKGROUND: Inflammatory processes and infections of the uterine wall must be
      accepted as a physiological event in dairy cows after calving. This might result
      in clinical or subclinical endometritis which is assumed to impair reproductive
      performance in the current lactation. Several cytokines and acute phase proteins
      have been discussed as local and systemic mediators of these inflammatory
      processes. The aim of the present study was to investigate the endometrial mRNA
      expression of the chemokine CXC ligand 5 (CXCL5), interleukin 1beta (IL1B), IL6,
      IL8, tumour necrosis factor alpha (TNF), prostaglandin-endoperoxide synthase 2
      (PTGS2) and haptoglobin (HP) in the postpartum period. METHODS: Endometrial
      samples were obtained from primiparous cows (n = 5) on days 10, 17, 24, 31, 38
      and 45 postpartum (pp) using the cytobrush technique. Cytological smears were
      prepared from cytobrush samples to determine the proportion of polymorphonuclear
      neutrophils (PMN). Total RNA was extracted from endometrial samples, and real
      time RT-PCR was performed. RESULTS: A time-dependent mRNA expression of the
      investigated factors was found for the course of the postpartum period. In
      detail, a significantly higher expression of these factors was observed on day 17
      pp compared to day 31 pp. Furthermore, the proportion of PMN peaked between days
      10-24 pp and decreased thereafter to low percentages (< 5%) on day 31 pp and
      thereafter. In addition, CXCL5, IL1B, IL8 and HP mRNA expression correlated
      significantly with the proportion of PMN (P < 0.05). A significantly higher
      CXCL5, IL1B, IL6, IL8, PTGS2 and TNF mRNA content was observed in samples from
      cows with an inflamed endometrium compared with samples from cows with a healthy
      endometrium (P < 0.05). CONCLUSIONS: These results show that inflammatory
      cytokines and acute phase proteins are expressed in the bovine endometrium in a
      time-related manner during the postpartum period, with a significant expression
      peak on day 17 pp as a possible mucosal immune response in the uterus. The
      evaluation of the expression patterns of such candidate genes may reveal more
      information than only determining the percentage of PMN to judge the severity of
      an inflammation.

PMID- 21176182
TI  - Oxygen supplementation facilitating successful prosthetic fitting and
      rehabilitation of a patient with severe chronic obstructive pulmonary disease
      following trans-tibial amputation: a case report.
AB  - INTRODUCTION: Dysvascular amputations are increasingly performed in patients with
      underlying cardiac and pulmonary disorders. A limb prosthesis is rarely offered
      to patients with severe chronic obstructive pulmonary disease because of their
      inability to achieve the high energy expenditure required for prosthetic
      ambulation. We describe a case of successful prosthetic fitting and
      rehabilitation of a patient with severe chronic obstructive pulmonary disease
      with the aid of oxygen supplementation. CASE PRESENTATION: A 67-year-old
      aboriginal woman with severe chronic obstructive pulmonary disease and
      hypercapnic respiratory failure underwent right trans-tibial (below the knee)
      amputation for severe foot gangrene. An aggressive rehabilitation program of
      conditioning exercises and gait training utilizing oxygen therapy was initiated.
      She was custom-fitted with a right trans-tibial prosthesis. A rehabilitation
      program improved her strength, endurance and stump contracture, and she was able
      to walk for short distances with the prosthesis. The motion analysis studies
      showed a cadence of 73.5 steps per minute, a velocity of 0.29 meters per second
      and no difference in right and left step time and step length. CONCLUSION: This
      case report illustrates that patients with significant severe chronic obstructive
      pulmonary disease can be successfully fitted with limb prostheses and undergo
      rehabilitation using supplemental oxygen along with optimization of their
      underlying comorbidities. Despite the paucity of published information in this
      area, prosthesis fitting and rehabilitation should be considered in patients who
      have undergone amputation and have severe chronic obstructive disease.

PMID- 21176183
TI  - Patterns of sequence polymorphism in the fleshless berry locus in cultivated and
      wild Vitis vinifera accessions.
AB  - BACKGROUND: Unlike in tomato, little is known about the genetic and molecular
      control of fleshy fruit development of perennial fruit trees like grapevine
      (Vitis vinifera L.). Here we present the study of the sequence polymorphism in a
      1 Mb grapevine genome region at the top of chromosome 18 carrying the fleshless
      berry mutation (flb) in order, first to identify SNP markers closely linked to
      the gene and second to search for possible signatures of domestication. RESULTS:
      In total, 62 regions (17 SSR, 3 SNP, 1 CAPS and 41 re-sequenced gene fragments)
      were scanned for polymorphism along a 3.4 Mb interval (85,127-3,506,060 bp) at
      the top of the chromosome 18, in both V. vinifera cv. Chardonnay and a genotype
      carrying the flb mutation, V. vinifera cv. Ugni Blanc mutant. A nearly complete
      homozygosity in Ugni Blanc (wild and mutant forms) and an expected high level of
      heterozygosity in Chardonnay were revealed. Experiments using qPCR and BAC FISH
      confirmed the observed homozygosity. Under the assumption that flb could be one
      of the genes involved into the domestication syndrome of grapevine, we sequenced
      69 gene fragments, spread over the flb region, representing 48,874 bp in a highly
      diverse set of cultivated and wild V. vinifera genotypes, to identify possible
      signatures of domestication in the cultivated V. vinifera compartment. We
      identified eight gene fragments presenting a significant deviation from
      neutrality of the Tajima's D parameter in the cultivated pool. One of these also
      showed higher nucleotide diversity in the wild compartments than in the
      cultivated compartments. In addition, SNPs significantly associated to berry
      weight variation were identified in the flb region. CONCLUSIONS: We observed the
      occurrence of a large homozygous region in a non-repetitive region of the
      grapevine otherwise highly-heterozygous genome and propose a hypothesis for its
      formation. We demonstrated the feasibility to apply BAC FISH on the very small
      grapevine chromosomes and provided a specific probe for the identification of
      chromosome 18 on a cytogenetic map. We evidenced genes showing putative
      signatures of selection and SNPs significantly associated with berry weight
      variation in the flb region. In addition, we provided to the community 554 SNPs
      at the top of chromosome 18 for the development of a genotyping chip for future
      fine mapping of the flb gene in a F2 population when available.

PMID- 21176184
TI  - Diagnostic utility of alpha-methylacyl CoA racemase (P504S) & HMWCK in
      morphologically difficult prostate cancer.
AB  - BACKGROUND: To evaluate the diagnostic utility of alpha-methylacyl CoA racemase
      (P504S) & HMWCK (34beta E12) in morphologically difficult prostate cancer.
      METHODS: A total of 1034 cases were reviewed and divided into benign (585)
      malignant (399) and suspicious (50). Immunohistochemistry with HMWCK and AMACR
      was done on the 50 suspicious cases along with controls. RESULTS: Forty nine
      suspicious cases were resolved by using both markers where as 1 case was resolved
      by further support with CD68. The original diagnosis was changed in 15 of 50
      (30%) suspicious cases from benign to malignant, one case from benign to high
      grade PIN and in one case from malignant to benign. Change of diagnosis was seen
      in 17 of 50 (34%) suspicious cases with a significant p value of 0.002. The
      overall diagnosis was changed in 17 of 1034 cases (1.64%) of prostatic disease (p
      < 0.001). CONCLUSIONS: A combination of HMWCK and AMACR is of great value in
      combating the morphologically suspicious cases and significantly increasing the
      diagnostic accuracy in prostate cancer. Although, in this study the sensitivity
      and specificity of HMWCK and AMACR were high, yet it should be used with caution,
      keeping in mind all their pitfalls and limitations.

PMID- 21176185
TI  - Twin reversed arterial perfusion (TRAP) sequence in association with VACTERL
      association: a case report.
AB  - INTRODUCTION: Twin reversed arterial perfusion (TRAP) sequence is a rare
      complication of multiple pregnancy caused by defects in early embryogenesis. The
      pump twin supplies the acardiac recipient twin with blood, and although the pump
      twin is usually structurally normal, congenital anomalies have sometimes been
      reported. We report a unique case of twin reversed arterial perfusion sequence
      with a prenatal diagnosis of VACTERL association in the surviving pump twin. CASE
      PRESENTATION: A 24-year-old Caucasian woman presented at 11 weeks' gestation with
      a monochorionic, monoamniotic twin pregnancy. A reversed arterial flow was noted
      on a Doppler imaging study coming from the larger, apparently normal twin to the
      smaller, grossly abnormal twin, and a diagnosis of twin reversed arterial
      perfusion sequence was made. Cardiac activity was undetectable in the recipient
      twin by 16 weeks' gestation. Further detailed assessment at 18 weeks' gestation
      revealed multiple congenital anomalies of the surviving pump twin, in keeping
      with a diagnosis of VACTERL association. A live infant girl was delivered at 39
      weeks by elective cesarean section. She underwent extensive surgery with
      subsequent normal development at the age of two years. CONCLUSION: The co
      existence of two rare and complex conditions in this unique case raises
      interesting questions about the role of early defects in embryogenesis and their
      subsequent effects on fetal development. This case also highlights the importance
      of prenatal diagnosis of major congenital anomalies to the plan treatment, reduce
      morbidity and aid the survival of affected children.

PMID- 21176187
TI  - Placenta increta causing hemoperitoneum in the 26th week of pregnancy: a case
      report.
AB  - INTRODUCTION: Placenta increta is a serious complication of pregnancy. We
      describe a case leading to uterine rupture associated with massive intra
      abdominal hemorrhage. CASE PRESENTATION: A 34-year-old Caucasian Albanian woman,
      gravida 2, para 1, was admitted to the emergency department of our hospital for
      acute abdominal pain associated with profound secondary anemia. An
      anatomopathological diagnosis of placenta increta destruens was made. An urgent
      hysterectomy was performed after resuscitation procedures, applied due to the
      severe anemia and the abdominal drama accompanying the case. Intra-operatively, a
      uterus-saving procedure was found to be impossible, and hysterectomy remained the
      only surgical option. The uterine structures were sent for further microscopic
      evaluation. On histological examination, deep trophoblastic infiltration of the
      uterine wall was observed, justifying the surgeon's decision. Our patient
      received blood transfusions and antibiotics. Her sutures were removed on the
      eighth postoperative day and she was discharged the following day in a stable
      condition. CONCLUSION: This case, describing a patient with uterine rupture and
      massive hemorrhage, illustrates a serious and potentially fatal complication of
      placenta previa. In such cases, surgery is essential, and hysterectomy may be the
      only viable option.

PMID- 21176186
TI  - Oxidative modification of albumin in the parenchymal lung tissue of current
      smokers with chronic obstructive pulmonary disease.
AB  - BACKGROUND: There is accumulating evidence that oxidative stress plays an
      important role in the pathophysiology of chronic obstructive pulmonary disease
      (COPD). One current hypothesis is that the increased oxidant burden in these
      patients is not adequately counterbalanced by the lung antioxidant systems.
      OBJECTIVE: To determine the levels of oxidised human serum albumin (HSA) in COPD
      lung explants and the effect of oxidation on HSA degradation using an ex vivo
      lung explant model. METHODS: Parenchymal lung tissue was obtained from 38
      patients (15F/23M) undergoing lung resection and stratified by smoking history
      and disease using the GOLD guidelines and the lower limit of normal for FEV1/FVC
      ratio. Lung tissue was homogenised and analysed by ELISA for total levels of HSA
      and carbonylated HSA. To determine oxidised HSA degradation lung tissue explants
      were incubated with either 200 MUg/ml HSA or oxidised HSA and supernatants
      collected at 1, 2, 4, 6, and 24 h and analysed for HSA using ELISA and
      immunoblot. RESULTS: When stratified by disease, lung tissue from GOLD II (median
      = 38.2 MUg/ml) and GOLD I (median = 48.4 MUg/ml) patients had lower levels of HSA
      compared to patients with normal lung function (median = 71.9 MUg/ml, P < 0.05).
      In addition the number of carbonyl residues, which is a measure of oxidation was
      elevated in GOLD I and II tissue compared to individuals with normal lung
      function (P < 0.05). When analysing smoking status current smokers had lower
      levels of HSA (median = 43.3 MUg/ml, P < 0.05) compared to ex smokers (median =
      71.9 MUg/ml) and non-smokers (median = 71.2 MUg/ml) and significantly greater
      number of carbonyl residues per HSA molecule (P < 0.05). When incubated with
      either HSA or oxidised HSA lung tissue explants rapidly degraded the oxidised HSA
      but not unmodified HSA (P < 0.05). CONCLUSION: We report on a reliable
      methodology for measuring levels of oxidised HSA in human lung tissue and cell
      culture supernatant. We propose that differences in the levels of oxidised HSA
      within lung tissue from COPD patients and current smokers provides further
      evidence for an oxidant/antioxidant imbalance and has important biological
      implications for the disease.

PMID- 21176188
TI  - Successful treatment of metastatic hepatic epithelioid hemangioendothelioma with
      thalidomide: a case report.
AB  - INTRODUCTION: Hepatic epithelioid hemangioendothelioma is a rare malignancy
      arising from the vascular endothelial cells within the liver. Historically, the
      disease is characterized as being poorly responsive to both chemotherapy and
      radiotherapy, with liver resection or transplantation the treatment of choice
      when feasible. For patients with advanced disease, reports of long-term
      therapeutic benefits from conventional cytotoxic treatments are very limited.
      Owing to the rarity of this malignancy, there is no structured therapeutic
      research, but a small number of cases have been reported to respond well to
      treatment with inhibitors of angiogenesis. Thalidomide was originally developed
      as an anti-emetic but is a potent inhibitor of vascular neogenesis, and could
      offer potential in the treatment of hepatic epithelioid hemangioendothelioma by
      blocking the proliferation of the malignant vascular endothelial cells. CASE
      PRESENTATION: We describe the case of a Caucasian British woman who presented at
      the age of 53 years with a hepatic mass, malignant lymphadenopathy and pulmonary
      metastases, which were confirmed as hepatic epithelioid hemangioendothelioma on
      biopsy. After unproductive treatment with interferon, our patient was started on
      thalidomide 400 mg daily. She has been successfully managed on this therapy for
      the past seven years, and has remained asymptomatic, with radiologically stable
      disease and minimal treatment-related side effects. CONCLUSION: At present, there
      is no standard therapy for advanced hepatic epithelioid hemangioendothelioma. Our
      case supports the role for thalidomide and potentially other inhibitors of
      vascular neogenesis in the treatment of patients with metastatic hepatic
      epithelioid hemangioendothelioma.

PMID- 21176190
TI  - Perception and management of fever in infants up to six months of age: a survey
      of US pediatricans.
AB  - BACKGROUND: A fever is an increase in the body's temperature above normal. This
      study examined how US pediatricians perceive and manage fever generally versus
      fever occurring after vaccination in infants up to six months of age. METHODS: A
      web-based survey of 400 US pediatricians subscribing to the Physician Desk
      Reference was conducted in December 2008. Data were collected on the respondents'
      socio-demographics, number of years in practice, type of practice, their
      definition of fever severity in infants, and their recommendations for managing
      fever. Generalized Estimating Equations were used to estimate the odds of a
      pediatrician recommending an emergency room visit (ER) or a hospital admission,
      office visits, or other treatment option, as a function of infant's age,
      temperature, whether the infant has recently received a vaccine, and whether the
      fever was reported during or after office hours, adjusting for practice type and
      socio-demographic variables. RESULTS: On average, the 400 responding
      pediatricians' (64% were female, average age of 49 years, years in practice = 20
      years) threshold for extremely serious fever was >=39.5 degrees C and >= 40.0
      degrees C for infants 0-2 month and >2-6 month of age respectively. Infants were
      more likely to be referred to an ER or hospital admission if they were <= 2
      months of age (Odds Ratio [OR], 29.13; 95% Confidence interval [95% CI], 23.69
      35.82) or >2-4 months old (OR 3.37; 95% CI 2.99-3.81) versus > 4 to 6 months old
      or if they had a temperature >= 40.0 degrees C (OR 21.06; 95% CI 17.20-25.79)
      versus a temperature of 38.0-38.5 degrees C. Fever after vaccination (OR 0.29;
      95% CI 0.25-0.33) or reported during office hours (OR 0.17; 95% CI 0.15-0.20)
      were less likely to result in referral to ER or hospital admission. CONCLUSION:
      Within this sample of US pediatricians, perception of the severity of fever in
      infants, as well as the response to infant fever are likely to depend on the
      infant's age. Recommendations for the management of fever in infants are likely
      to depend on fever severity level, the infant age, timing in relation to recent
      vaccination, and the time of day fever is reported. Our results indicate that US
      pediatricians are more concerned about general fever than fever following
      vaccination.

PMID- 21176189
TI  - Diagnosis and biomarkers of predementia in Alzheimer's disease.
AB  - In view of the growing prevalence of Alzheimer's disease (AD) worldwide, there is
      an urgent need for the development of better diagnostic tools and more effective
      therapeutic interventions. At the earliest stages of AD, no significant cognitive
      or functional impairment is detected by conventional clinical methods. However,
      new technologies based on structural and functional neuroimaging, and on the
      biochemical analysis of cerebrospinal fluid (CSF) may reveal correlates of
      intracerebral pathology in individuals with mild, predementia symptoms. These
      putative correlates are commonly referred to as AD-related biomarkers. The
      relevance of the early diagnosis of AD relies on the hypothesis that
      pharmacological interventions with disease-modifying compounds are likely to
      produce clinically relevant benefits if started early enough in the continuum
      towards dementia. Here we review the clinical characteristics of the prodromal
      and transitional states from normal cognitive ageing to dementia in AD. We
      further address recent developments in biomarker research to support the early
      diagnosis and prediction of dementia, and point out the challenges and
      perspectives for the translation of research data into clinical practice.

PMID- 21176191
TI  - Withdrawal users' experiences of and attitudes to contraceptive methods: a study
      from Eastern district of Tehran, Iran.
AB  - BACKGROUND: The aim of this study was to explore withdrawal users' experiences of
      and attitudes to contraceptive methods in Tehran, Iran. METHODS: This was a cross
      sectional study. A sample of women attending a health care center in Tehran, Iran
      was entered into the study. To collect data structured interviews were conducted.
      RESULTS: In all 300 women who were using withdrawal took part in the study. Of
      these, 210 women (70%) indicated that they were used modern contraceptive methods
      previously. The mean duration for withdrawal use was 6.5 (SD = 4.9) and for
      modern contraceptive it was 2.3 (SD = 2.9) years. The most common reasons for
      using withdrawal were: no cost involvement, did not need medical advice, having
      fewer side effects and easier to use than other methods. The main obstacles to
      use modern contraceptives were: health concerns, fear of side effects,
      misinformation, lack of confidence and sexual dissatisfaction. CONCLUSION: The
      study results suggest that withdrawal users carry misconceptions about modern
      contraception and exaggerate its related health problems. Indeed these are
      important issues for the understanding of attitudes and experiences of women in
      Iran. The findings from this study might be essential for making evidence-based
      policy decisions, and for planning, monitoring and evaluating reproductive health
      programs in Iran and elsewhere.

PMID- 21176192
TI  - Perforated mixed carcinoid-adenocarcinoma in transverse colon and at
      gastroenterostomy site: case report.
AB  - Goblet cell carcinoid of the large intestine is a rare neoplasm, usually located
      in ascending colon and rectum. A 60-year-old male patient underwent surgery after
      the diagnosis of acute abdomen. Exploratory laparotomy revealed perforation with
      a diameter of 1 cm at the site of the previously performed gastroenterostomy and
      dilatation of the right colic flexure, secondary to a solid obstructive mass
      located in the mid-portion of transverse colon. Histopathological investigation
      of the biopsies, taken from the gastroenterostomy site and the tumor, revealed
      mixed carcinoid-adenocarcinoma with carcinoid component, predominantly composed
      of goblet cells. Three cycles of FOLFOX-4 protocol was administered. Following
      respiratory distress secondary to pulmonary metastasis, the patient's condition
      deteriorated and subsequently died in the fourth postoperative month. Our aim
      with this paper is to point out that more cases should be reported for more
      effective diagnosis, histopathological study, clinical investigation, treatment
      and prognosis of this specific neoplasm.

PMID- 21176193
TI  - Micro-computed tomography of pulmonary fibrosis in mice induced by adenoviral
      gene transfer of biologically active transforming growth factor-beta1.
AB  - BACKGROUND: Micro-computed tomography (micro-CT) is a novel tool for monitoring
      acute and chronic disease states in small laboratory animals. Its value for
      assessing progressive lung fibrosis in mice has not been reported so far. Here we
      examined the importance of in vivo micro-CT as non-invasive tool to assess
      progression of pulmonary fibrosis in mice over time. METHODS: Pulmonary fibrosis
      was induced in mice by intratracheal delivery of an adenoviral gene vector
      encoding biologically active TGF-beta1 (AdTGF-beta1). Respiratory gated and
      ungated micro-CT scans were performed at 1, 2, 3, and 4 weeks post pulmonary
      adenoviral gene or control vector delivery, and were then correlated with
      respective histopathology-based Ashcroft scoring of pulmonary fibrosis in mice.
      Visual assessment of image quality and consolidation was performed by 3 observers
      and a semi-automated quantification algorithm was applied to quantify aerated
      pulmonary volume as an inverse surrogate marker for pulmonary fibrosis. RESULTS:
      We found a significant correlation between classical Ashcroft scoring and micro
      CT assessment using both visual assessment and the semi-automated quantification
      algorithm. Pulmonary fibrosis could be clearly detected in micro-CT, image
      quality values were higher for respiratory gated exams, although differences were
      not significant. For assessment of fibrosis no significant difference between
      respiratory gated and ungated exams was observed. CONCLUSIONS: Together, we show
      that micro-CT is a powerful tool to assess pulmonary fibrosis in mice, using both
      visual assessment and semi-automated quantification algorithms. These data may be
      important in view of pre-clinical pharmacologic interventions for the treatment
      of lung fibrosis in small laboratory animals.

PMID- 21176194
TI  - Steady-state mycophenolate mofetil pharmacokinetic parameters enable prediction
      of systemic lupus erythematosus clinical flares: an observational cohort study.
AB  - INTRODUCTION: The aim of this study was to determine whether mycophenolate
      mofetil (MMF) pharmacokinetics (PK) under combined MMF and prednisone remission
      maintenance therapy can predict systemic lupus erythematosus (SLE) clinical
      flares. METHODS: At inclusion, steady-state PK parameters of the MMF active form,
      mycophenolic acid (MPA), and its glucuronide metabolite (MPAG) were determined
      for 25 stable SLE patients without renal manifestations. Disease activity was
      assessed during 6 months of follow-up. Potential relationships between those
      entry MMF-PK variables and clinical outcome were analyzed. RESULTS: MMF
      controlled disease activity in 17 patients (successes) and failed to do so for 8
      others (failures). For failures and successes, respectively, entry MPA areas
      under the time-concentration curve between 0 and 12 hours (AUC(0-12 h)) (medians:
      37.7 vs 73.1 mg/h/L, P = 0.003) and MPA 12-hour trough concentrations (C(12 h))
      (medians: 1.5 vs 3.7 mg/L, P = 0.008) were significantly lower, and inclusion
      MPAG/MPA C(12 h) ratios (medians: 18.7 vs 10.2, P = 0.02) were significantly
      higher. According to our receiver operating characteristics curve analysis, MPA
      C(12 h) was best able to discriminate a flare during follow-up (93% sensitivity,
      85% specificity). A 3-mg/L cut-off had 92% negative-predictive value for
      developing a flare during follow-up. CONCLUSIONS: For our SLE patients without
      renal manifestations, clinical flares developing under maintenance therapy were
      associated with steady-state inclusion MPA C(12 h) < 3 mg/L.

PMID- 21176195
TI  - The xenotropic murine leukemia virus-related retrovirus debate continues at first
      international workshop.
AB  - The 1st International Workshop on Xenotropic Murine Leukemia Virus-Related
      Retrovirus (XMRV), co-sponsored by the National Institutes of Health, The
      Department of Health and Human Services and Abbott Diagnostics, was convened on
      September 7/8, 2010 on the NIH campus, Bethesda, MD. Attracting an international
      audience of over 200 participants, the 2-day event combined a series of plenary
      talks with updates on different aspects of XMRV research, addressing basic
      gammaretrovirus biology, host response, association of XMRV with chronic fatigue
      syndrome and prostate cancer, assay development and epidemiology. The current
      status of XMRV research, concerns among the scientific community and suggestions
      for future actions are summarized in this meeting report.

PMID- 21176196
TI  - The FANTASTIC FOUR proteins influence shoot meristem size in Arabidopsis
      thaliana.
AB  - BACKGROUND: Throughout their lives plants produce new organs from groups of
      pluripotent cells called meristems, located at the tips of the shoot and the
      root. The size of the shoot meristem is tightly controlled by a feedback loop,
      which involves the homeodomain transcription factor WUSCHEL (WUS) and the CLAVATA
      (CLV) proteins. This regulatory circuit is further fine-tuned by morphogenic
      signals such as hormones and sugars. RESULTS: Here we show that a family of four
      plant-specific proteins, encoded by the FANTASTIC FOUR (FAF) genes, has the
      potential to regulate shoot meristem size in Arabidopsis thaliana. FAF2 and FAF4
      are expressed in the centre of the shoot meristem, overlapping with the site of
      WUS expression. Consistent with a regulatory interaction between the FAF gene
      family and WUS, our experiments indicate that the FAFs can repress WUS, which
      ultimately leads to an arrest of meristem activity in FAF overexpressing lines.
      The finding that meristematic expression of FAF2 and FAF4 is under negative
      control by CLV3 further supports the hypothesis that the FAFs are modulators of
      the genetic circuit that regulates the meristem. CONCLUSION: This study reports
      the initial characterization of the Arabidopsis thaliana FAF gene family. Our
      data indicate that the FAF genes form a plant specific gene family, the members
      of which have the potential to regulate the size of the shoot meristem by
      modulating the CLV3-WUS feedback loop.

PMID- 21176197
TI  - Community response to intermittent preventive treatment of malaria in infants
      (IPTi) in Papua New Guinea.
AB  - BACKGROUND: Building on previous acceptability research undertaken in sub-Saharan
      Africa this article aims to investigate the acceptability of intermittent
      preventive treatment of malaria in infants (IPTi) in Papua New Guinea (PNG).
      METHODS: A questionnaire was administered to mothers whose infants participated
      in the randomised placebo controlled trial of IPTi. Mothers whose infants
      participated and who refused to participate in the trial, health workers,
      community reporters and opinion leaders were interviewed. Men and women from the
      local community also participated in focus group discussions. RESULTS:
      Respondents viewed IPTi as acceptable in light of wider concern for infant health
      and the advantages of trial participation. Mothers reported complying with at
      home administration of IPTi due to perceived benefits of IPTi and pressure from
      health workers. In spite of patchy knowledge, respondents also demonstrated a
      demand for infant vaccinations and considered non-vaccination to be neglect.
      There is little evidence that IPTi has negative impacts on attitudes to EPI, EPI
      adherence or existing malaria prevention practices. CONCLUSION: The degree of
      similarity between findings from the acceptability studies undertaken in sub
      Saharan Africa and PNG allows some generalization relating to the implementation
      of IPTi outside of Africa: IPTi fits well with local health cultures, appears to
      be accepted easily and has little impact on attitudes towards EPI or malaria
      prevention. The study adds to the evidence indicating that IPTi could be rolled
      out in a range of social and cultural contexts.

PMID- 21176198
TI  - Pathologic fracture and metastatic spinal cord compression in patients with
      prostate cancer and bone metastases.
AB  - BACKGROUND: The purpose of this study was to determine the risk factors for and
      incidence as well as prognostic impact of pathologic fracture (PF) and metastatic
      spinal cord compression (MSCC) in patients with bone metastases (BM) from
      prostate cancer. METHODS: Retrospective cohort study including 61 consecutive
      patients seen at Nordland hospital's department of oncology between 2007 and
      2009. The initial diagnosis of BM might have been made earlier. Twenty-nine
      patients (48%) received taxotere and 72% zoledronic acid after diagnosis of BM.
      RESULTS: Median actuarial survival after diagnosis of BM was 23 months. Six
      patients (10%) were alive at 5 years. Bone pain at baseline was present in 49% of
      patients. Eighty-nine percent required external beam radiotherapy and/or
      radioisotopes after diagnosis of BM. Seventeen patients (28%) developed at least
      one major skeletal complication, i.e. MSCC or PF (4 of them developed more than
      one). The actuarial risk was 44% at 4 and 5 years. Most events developed before
      treatment with zoledronic acid and/or taxotere. Median survival from diagnosis of
      either MSCC or PF was 11 months (5 months from MSCC). We did not identify
      statistically significant risk factors for development of major skeletal
      complications. Serum alkaline phosphatase above median value and age less than or
      equal to 70 years were the only risk factors approaching significance.
      CONCLUSIONS: We found high rates of major skeletal complications in this
      unselected contemporary group of patients. Identification of risk factors might
      guide the development of early interventions aiming at prevention of MSCC and PF.

PMID- 21176199
TI  - The complexity of gene expression dynamics revealed by permutation entropy.
AB  - BACKGROUND: High complexity is considered a hallmark of living systems. Here we
      investigate the complexity of temporal gene expression patterns using the concept
      of Permutation Entropy (PE) first introduced in dynamical systems theory. The
      analysis of gene expression data has so far focused primarily on the
      identification of differentially expressed genes, or on the elucidation of
      pathway and regulatory relationships. We aim to study gene expression time series
      data from the viewpoint of complexity. RESULTS: Applying the PE complexity metric
      to abiotic stress response time series data in Arabidopsis thaliana, genes
      involved in stress response and signaling were found to be associated with the
      highest complexity not only under stress, but surprisingly, also under reference,
      non-stress conditions. Genes with house-keeping functions exhibited lower PE
      complexity. Compared to reference conditions, the PE of temporal gene expression
      patterns generally increased upon stress exposure. High-complexity genes were
      found to have longer upstream intergenic regions and more cis-regulatory motifs
      in their promoter regions indicative of a more complex regulatory apparatus
      needed to orchestrate their expression, and to be associated with higher
      correlation network connectivity degree. Arabidopsis genes also present in other
      plant species were observed to exhibit decreased PE complexity compared to
      Arabidopsis specific genes. CONCLUSIONS: We show that Permutation Entropy is a
      simple yet robust and powerful approach to identify temporal gene expression
      profiles of varying complexity that is equally applicable to other types of
      molecular profile data.

PMID- 21176200
TI  - Prevalence and association between obesity and metabolic syndrome among Chinese
      elementary school children: a school-based survey.
AB  - BACKGROUND: China has experienced an increase in the prevalence of childhood
      overweight/obesity over the last decades. The purpose of this study was to
      examine the prevalence of obesity and metabolic syndrome among Chinese school
      children and determine if there is a significant association between childhood
      obesity and metabolic syndrome. METHODS: A cross-sectional study was conducted
      among 1844 children (938 males and 906 females) in six elementary schools at
      Guangzhou city from April to June 2009. The body mass index (BMI), waist
      circumference, blood pressure, Tanner stage, lipids, insulin and glucose levels
      were determined. Criteria analogous to ATPIII were used for diagnosis of
      metabolic syndrome in children. RESULTS: Among 1844 children aged 7-14 years, 205
      (11.1%) were overweight, and 133 (7.2%) were obese. The prevalence of metabolic
      syndrome was 6.6% overall, 33.1% in obese, 20.5% in overweight and 2.3% in normal
      weight children. Multiple logistic regression analysis showed that BMI (3rd
      quartile)(OR 3.28; 95%CI 0.35-30.56), BMI (4th quartile)(OR 17.98; 95%CI 1.75
      184.34), homeostasis model assessment (HOMA-IR) (2nd quartile) (OR2.36; 95% CI
      0.46-12.09), HOMA-IR (3rd quartile) (OR 2.46; 95% CI 0.48-12.66), HOMA-IR (4th
      quartile) (OR3.87; 95% CI 0.72-20.71) were significantly associated with
      metabolic syndrome. CONCLUSIONS: The current epidemic of obesity with subsequent
      increasing cardiovascular risk factors has constituted a threat to the health of
      school children in China. HOMA-IR and BMI were strong predictors of metabolic
      syndrome in children. Therefore, rigorous obesity prevention programs should be
      implemented among them.

PMID- 21176201
TI  - Horizontal acquisition of multiple mitochondrial genes from a parasitic plant
      followed by gene conversion with host mitochondrial genes.
AB  - BACKGROUND: Horizontal gene transfer (HGT) is relatively common in plant
      mitochondrial genomes but the mechanisms, extent and consequences of transfer
      remain largely unknown. Previous results indicate that parasitic plants are often
      involved as either transfer donors or recipients, suggesting that direct contact
      between parasite and host facilitates genetic transfer among plants. RESULTS: In
      order to uncover the mechanistic details of plant-to-plant HGT, the extent and
      evolutionary fate of transfer was investigated between two groups: the parasitic
      genus Cuscuta and a small clade of Plantago species. A broad polymerase chain
      reaction (PCR) survey of mitochondrial genes revealed that at least three genes
      (atp1, atp6 and matR) were recently transferred from Cuscuta to Plantago.
      Quantitative PCR assays show that these three genes have a mitochondrial location
      in the one species line of Plantago examined. Patterns of sequence evolution
      suggest that these foreign genes degraded into pseudogenes shortly after transfer
      and reverse transcription (RT)-PCR analyses demonstrate that none are detectably
      transcribed. Three cases of gene conversion were detected between native and
      foreign copies of the atp1 gene. The identical phylogenetic distribution of the
      three foreign genes within Plantago and the retention of cytidines at ancestral
      positions of RNA editing indicate that these genes were probably acquired via a
      single, DNA-mediated transfer event. However, samplings of multiple individuals
      from two of the three species in the recipient Plantago clade revealed complex
      and perplexing phylogenetic discrepancies and patterns of sequence divergence for
      all three of the foreign genes. CONCLUSIONS: This study reports the best evidence
      to date that multiple mitochondrial genes can be transferred via a single HGT
      event and that transfer occurred via a strictly DNA-level intermediate. The
      discovery of gene conversion between co-resident foreign and native mitochondrial
      copies suggests that transferred genes may be evolutionarily important in
      generating mitochondrial genetic diversity. Finally, the complex relationships
      within each lineage of transferred genes imply a surprisingly complicated history
      of these genes in Plantago subsequent to their acquisition via HGT and this
      history probably involves some combination of additional transfers (including
      intracellular transfer), gene duplication, differential loss and mutation-rate
      variation. Unravelling this history will probably require sequencing multiple
      mitochondrial and nuclear genomes from Plantago. See Commentary:
      http://www.biomedcentral.com/1741-7007/8/147.

PMID- 21176202
TI  - A high-throughput chemically induced inflammation assay in zebrafish.
AB  - BACKGROUND: Studies on innate immunity have benefited from the introduction of
      zebrafish as a model system. Transgenic fish expressing fluorescent proteins in
      leukocyte populations allow direct, quantitative visualization of an inflammatory
      response in vivo. It has been proposed that this animal model can be used for
      high-throughput screens aimed at the identification of novel immunomodulatory
      lead compounds. However, current assays require invasive manipulation of fish
      individually, thus preventing high-content screening. RESULTS: Here we show that
      specific, noninvasive damage to lateral line neuromast cells can induce a robust
      acute inflammatory response. Exposure of fish larvae to sublethal concentrations
      of copper sulfate selectively damages the sensory hair cell population inducing
      infiltration of leukocytes to neuromasts within 20 minutes. Inflammation can be
      assayed in real time using transgenic fish expressing fluorescent proteins in
      leukocytes or by histochemical assays in fixed larvae. We demonstrate the
      usefulness of this method for chemical and genetic screens to detect the effect
      of immunomodulatory compounds and mutations affecting the leukocyte response.
      Moreover, we transformed the assay into a high-throughput screening method by
      using a customized automated imaging and processing system that quantifies the
      magnitude of the inflammatory reaction. CONCLUSIONS: This approach allows rapid
      screening of thousands of compounds or mutagenized zebrafish for effects on
      inflammation and enables the identification of novel players in the regulation of
      innate immunity and potential lead compounds toward new immunomodulatory
      therapies. We have called this method the chemically induced inflammation assay,
      or ChIn assay. See Commentary article: http://www.biomedcentral.com/1741
      7007/8/148.

PMID- 21176203
TI  - Attention Deficit Hyperactivity Disorder (ADHD) among longer-term prison inmates
      is a prevalent, persistent and disabling disorder.
AB  - BACKGROUND: ADHD is a common and disabling disorder, with an increased risk for
      coexisting disorders, substance abuse and delinquency. In the present study, we
      aimed at exploring ADHD and criminality. We estimated the prevalence of ADHD
      among longer-term prison inmates, described symptoms and cognitive functioning,
      and compared findings with ADHD among psychiatric outpatients and healthy
      controls. METHODS: At Norrtalje Prison, we approached 315 male inmates for
      screening of childhood ADHD by the Wender Utah Rating Scale (WURS-25) and for
      present ADHD by the Adult ADHD Self-Report Screener (ASRS-Screener). The response
      rate was 62%. Further, we assessed 34 inmates for ADHD and coexisting disorders.
      Finally, we compared findings with 20 adult males with ADHD, assessed at a
      psychiatric outpatient clinic and 18 healthy controls. RESULTS: The estimated
      prevalence of adult ADHD among longer-term inmates was 40%. Only 2 out of 30
      prison inmates confirmed with ADHD had received a diagnosis of ADHD during
      childhood, despite most needed health services and educational support. All
      subjects reported lifetime substance use disorder (SUD) where amphetamine was the
      most common drug. Mood and anxiety disorders were present among half of subjects;
      autism spectrum disorder (ASD) among one fourth and psychopathy among one tenth.
      Personality disorders were common; almost all inmates presented conduct disorder
      (CD) before antisocial personality disorder (APD). Prison inmates reported more
      ADHD symptoms during both childhood and adulthood, compared with ADHD psychiatric
      outpatients. Further, analysis of executive functions after controlling for IQ
      showed both ADHD groups performed poorer than controls on working memory tests.
      Besides, on a continuous performance test, the ADHD prison group displayed poorer
      results compared with both other groups. CONCLUSIONS: This study suggested ADHD
      to be present among 40% of adult male longer-term prison inmates. Further, ADHD
      and coexisting disorders, such as SUD, ASD, personality disorders, mood- and
      anxiety disorders, severely affected prison inmates with ADHD. Besides, inmates
      showed poorer executive functions also when controlling for estimated IQ compared
      with ADHD among psychiatric outpatients and controls. Our findings imply the need
      for considering these severities when designing treatment programmes for prison
      inmates with ADHD.

PMID- 21176205
TI  - Bifidobacterium animalis AHC7 protects against pathogen-induced NF-kappaB
      activation in vivo.
AB  - BACKGROUND: Bifidobacteria and lactobacilli are among the early and important
      colonizers of the gastrointestinal tract and are generally considered to be part
      of a normal, healthy microbiota. It is believed that specific strains within the
      microbiota can influence host immune-reactivity and may play a role in protection
      from infection and aberrant inflammatory activity. One such strain,
      Bifidobacterium animalis AHC7, has been previously shown to protect against
      Salmonella typhimurium infection in mice and helps resolve acute idiopathic
      diarrhea in dogs. The aim of this study was to investigate the potential
      molecular and cellular mechanisms underpinning the Bifidobacterium animalis AHC7
      protective effect. RESULTS: Following 4 hours of infection with Salmonella
      typhimurium, NF-kappaB activation was significantly elevated in vivo in placebo
      and Enterococcus faecium-fed animals while Bifidobacterium animalis AHC7
      consumption significantly attenuated the NF-kappaB response. In vitro anti
      CD3/CD28 stimulated Peyer's patch cells secreted significantly less TNF-alpha and
      IFN-gamma following Bifidobacterium animalis AHC7 consumption. Stimulated cells
      released more IL-12p70 but this difference did not reach statistical
      significance. No alteration in mucosal IL-6, IL-10 or MCP-1 levels were observed.
      No statistically significant change in the cytokine profile of mesenteric lymph
      node cells was noted. In vitro, Bifidobacterium animalis AHC7 was bound by
      dendritic cells and induced secretion of both IL-10 and IL-12p70. In addition, co
      culture of CD4+ T cells with Bifidobacterium animalis AHC7-stimulated dendritic
      cells resulted in a significant increase in CD25+Foxp3+ T cell numbers.
      CONCLUSION: Bifidobacterium animalis AHC7 exerts an anti-inflammatory effect via
      the attenuation of pro-inflammatory transcription factor activation in response
      to an infectious insult associated with modulation of pro-inflammatory cytokine
      production within the mucosa. The cellular mechanism underpinning Bifidobacterium
      animalis AHC7 mediated attenuation of NF-kappaB activation may include
      recognition of the bacterium by dendritic cells and induction of CD25+Foxp3+ T
      cells.

PMID- 21176204
TI  - Drosophila EGFR pathway coordinates stem cell proliferation and gut remodeling
      following infection.
AB  - BACKGROUND: Gut homeostasis is central to whole organism health, and its
      disruption is associated with a broad range of pathologies. Following damage,
      complex physiological events are required in the gut to maintain proper
      homeostasis. Previously, we demonstrated that ingestion of a nonlethal pathogen,
      Erwinia carotovora carotovora 15, induces a massive increase in stem cell
      proliferation in the gut of Drosophila. However, the precise cellular events that
      occur following infection have not been quantitatively described, nor do we
      understand the interaction between multiple pathways that have been implicated in
      epithelium renewal. RESULTS: To understand the process of infection and
      epithelium renewal in more detail, we performed a quantitative analysis of
      several cellular and morphological characteristics of the gut. We observed that
      the gut of adult Drosophila undergoes a dynamic remodeling in response to
      bacterial infection. This remodeling coordinates the synthesis of new
      enterocytes, their proper morphogenesis and the elimination of damaged cells
      through delamination and anoikis. We demonstrate that one signaling pathway, the
      epidermal growth factor receptor (EGFR) pathway, is key to controlling each of
      these steps through distinct functions in intestinal stem cells and enterocytes.
      The EGFR pathway is activated by the EGF ligands, Spitz, Keren and Vein, the
      latter being induced in the surrounding visceral muscles in part under the
      control of the Janus kinase/signal transducer and activator of transcription
      (JAK/STAT) pathway. Additionally, the EGFR pathway synergizes with the JAK/STAT
      pathway in stem cells to promote their proliferation. Finally, we show that the
      EGFR pathway contributes to gut morphogenesis through its activity in enterocytes
      and is required to properly coordinate the delamination and anoikis of damaged
      cells. This function of the EGFR pathway in enterocytes is key to maintaining
      homeostasis, as flies lacking EGFR are highly susceptible to infection.
      CONCLUSIONS: This study demonstrates that restoration of normal gut morphology
      following bacterial infection is a more complex phenomenon than previously
      described. Maintenance of gut homeostasis requires the coordination of stem cell
      proliferation and differentiation, with the incorporation and morphogenesis of
      new cells and the expulsion of damaged enterocytes. We show that one signaling
      pathway, the EGFR pathway, is central to all these stages, and its activation at
      multiple steps could synchronize the complex cellular events leading to gut
      repair and homeostasis.

PMID- 21176206
TI  - Evaluation of best supportive care and systemic chemotherapy as treatment
      stratified according to the retrospective peritoneal surface disease severity
      score (PSDSS) for peritoneal carcinomatosis of colorectal origin.
AB  - BACKGROUND: We evaluate the long-term survival of patients with peritoneal
      carcinomatosis (PC) treated with systemic chemotherapy regimens, and the impact
      of the of the retrospective peritoneal disease severity score (PSDSS) on
      outcomes. METHODS: One hundred sixty-seven consecutive patients treated with PC
      from colorectal cancer between years 1987-2006 were identified from a prospective
      institutional database. These patients either received no chemotherapy, 5
      FU/Leucovorin or Oxaliplatin/Irinotecan-based chemotherapy. Stratification was
      made according to the retrospective PSDSS that classifies PC patients based on
      clinically relevant factors. Survival analysis was performed using the Kaplan
      Meier method and comparison with the log-rank test. RESULTS: Median survival was
      5 months (95% CI, 3-7 months) for patients who had no chemotherapy, 11 months
      (95% CI, 6-9 months) for patients treated with 5 FU/LV, and 12 months (95% CI, 4
      20 months) for patients treated with Oxaliplatin/Irinotecan-based chemotherapy.
      Survival differed between patients treated with chemotherapy compared to those
      patients who did not receive chemotherapy (p = 0.026). PSDSS staging was
      identified as an independent predictor for survival on multivariate analysis [RR
      2.8 (95%CI 1.5-5.4); p < 0.001]. CONCLUSION: A trend towards improved outcomes is
      demonstrated from treatment of patients with PC from colorectal cancer using
      modern systemic chemotherapy. The PSDSS appears to be a useful tool in patient
      selection and prognostication in PC of colorectal origin.

PMID- 21176207
TI  - Giemsa-stained thick blood films as a source of DNA for Plasmodium species
      specific real-time PCR.
AB  - BACKGROUND: This study describes the use of thick blood films (TBF) as specimens
      for DNA amplification with the Plasmodium species-specific real-time PCR that was
      recently validated on whole blood samples. METHODS: The panel of 135 Giemsa
      stained clinical TBFs represented single infections of the four Plasmodium
      species with varying parasite densities or only gametocytes, mixed infections,
      and negative samples and was stored for up to 12 years. Half of the Giemsa
      stained TBF was scraped off by a sterile scalpel and collected into phosphate
      buffered saline. DNA was extracted with the Qiagen DNA mini kit with minor
      modifications. DNA was amplified with the 18S rRNA real-time PCR targeting the
      four Plasmodium species with four species-specific primers and probes in
      combination with one genus-specific reverse primer. Results of the PCR on TBF
      were compared to those of the PCR on whole blood and to microscopy. RESULTS:
      Correct identification for single species infections was obtained for all TBF
      samples with Plasmodium falciparum (n = 50), Plasmodium vivax (n = 25),
      Plasmodium ovale (n = 25) and in all but one samples with Plasmodium malariae (n
      = 10). Compared to whole blood samples, higher Ct-values were observed by PCR on
      TBF with a mean difference of 5.93. Four out of five mixed infections were
      correctly identified with PCR on TBF. None of the negative samples (n = 20) gave
      a PCR signal. PCR on TBF showed a detection limit of 0.2 asexual parasites/MUl
      compared to 0.02/MUl for whole blood. Intra-run variation was higher for PCR on
      TBF (%CV 1.90) compared to PCR on whole blood (%CV 0.54). Compared to microscopy,
      PCR on TBF generated three more species identifications in samples containing a
      single species and detected the same four mixed-infections. CONCLUSIONS: Giemsa
      stained TBFs are a reliable source of DNA for Plasmodium real-time PCR analysis,
      allowing applications in reference and research settings in case whole blood
      samples are not available.

PMID- 21176208
TI  - Pica associated with iron deficiency or depletion: clinical and laboratory
      correlates in 262 non-pregnant adult outpatients.
AB  - BACKGROUND: There are many descriptions of the association of pica with iron
      deficiency in adults, but there are few reports in which observations available
      at diagnosis of iron deficiency were analyzed using multivariable techniques to
      identify significant predictors of pica. We sought to identify clinical and
      laboratory correlates of pica in adults with iron deficiency or depletion using
      univariable and stepwise forward logistic regression analyses. METHODS: We
      reviewed charts of 262 non-pregnant adult outpatients (ages >=18 y) who required
      treatment with intravenous iron dextran. We tabulated their sex, age,
      race/ethnicity, body mass index, symptoms and causes of iron deficiency or
      depletion, serum iron and complete blood count measures, and other conditions at
      diagnosis before intravenous iron dextran was administered. We excluded patients
      with serum creatinine >133 MUmol/L or disorders that could affect erythrocyte or
      iron measures. Iron deficiency was defined as both SF <45 pmol/L and TS <10%.
      Iron depletion was defined as serum ferritin (SF) <112 pmol/L. We performed
      univariable comparisons and stepwise forward logistic regression analyses to
      identify significant correlates of pica. RESULTS: There were 230 women (184
      white, 46 black; ages 19-91 y) and 32 men (31 white, 1 black; ages 24-81 y). 118
      patients (45.0%) reported pica; of these, 87.3% reported ice pica (pagophagia).
      In univariable analyses, patients with pica had lower mean age, black
      race/ethnicity, and higher prevalences of cardiopulmonary and epithelial
      manifestations. The prevalence of iron deficiency, with or without anemia, did
      not differ significantly between patients with and without pica reports. Mean
      hemoglobin and mean corpuscular volume (MCV) were lower and mean red blood cell
      distribution width (RDW) and platelet count were higher in patients with pica.
      Thrombocytosis occurred only in women and was more prevalent in those with pica
      (20.4% vs. 8.3%; p = 0.0050). Mean total iron-binding capacity was higher and
      mean serum ferritin was lower in patients with pica. Nineteen patients developed
      a second episode of iron deficiency or depletion; concordance of recurrent pica
      (or absence of pica) was 95%. Predictors of pica in logistic regression analyses
      were age and MCV (negative associations; p = 0.0250 and 0.0018, respectively) and
      RDW and platelet count (positive associations; p = 0.0009 and 0.02215,
      respectively); the odds ratios of these predictors were low. CONCLUSIONS: In non
      pregnant adult patients with iron deficiency or depletion, lower age is a
      significant predictor of pica. Patients with pica have lower MCV, higher RDW, and
      higher platelet counts than patients without pica.

PMID- 21176209
TI  - Possibility of multivariate function composed of plasma amino acid profiles as a
      novel screening index for non-small cell lung cancer: a case control study.
AB  - BACKGROUND: The amino-acid balance in cancer patients often differs from that in
      healthy individuals, because of metabolic changes. This study investigated the
      use of plasma amino-acid profiles as a novel marker for screening non-small-cell
      lung cancer (NSCLC) patients. METHODS: The amino-acid concentrations in venous
      blood samples from pre-treatment NSCLC patients (n = 141), and age-matched,
      gender-matched, and smoking status-matched controls (n = 423), were measured
      using liquid chromatography and mass spectrometry. The resultant study data set
      was subjected to multiple logistic regression analysis to identify amino acids
      related with NSCLC and construct the criteria for discriminating NSCLC patients
      from controls. A test data set derived from 162 patients and 3,917 controls was
      used to validate the stability of the constructed criteria. RESULTS: The plasma
      amino-acid profiles significantly differed between the NSCLC patients and the
      controls. The obtained model (including alanine, valine, isoleucine, histidine,
      tryptophan and ornithine concentrations) performed well, with an area under the
      curve of the receiver-operator characteristic curve (ROC_AUC) of >0.8, and
      allowed NSCLC patients and controls to be discriminated regardless of disease
      stage or histological type. CONCLUSIONS: This study shows that plasma amino acid
      profiling will be a potential screening tool for NSCLC.

PMID- 21176210
TI  - Pretreatment serum albumin as a predictor of cancer survival: a systematic review
      of the epidemiological literature.
AB  - BACKGROUND: There are several methods of assessing nutritional status in cancer
      of which serum albumin is one of the most commonly used. In recent years, the
      role of malnutrition as a predictor of survival in cancer has received
      considerable attention. As a result, it is reasonable to investigate whether
      serum albumin has utility as a prognostic indicator of cancer survival in cancer.
      This review summarizes all available epidemiological literature on the
      association between pretreatment serum albumin levels and survival in different
      types of cancer. METHODS: A systematic search of the literature using the MEDLINE
      database (January 1995 through June 2010) to identify epidemiologic studies on
      the relationship between serum albumin and cancer survival. To be included in the
      review, a study must have: been published in English, reported on data collected
      in humans with any type of cancer, had serum albumin as one of the or only
      predicting factor, had survival as one of the outcome measures (primary or
      secondary) and had any of the following study designs (case-control, cohort,
      cross-sectional, case-series prospective, retrospective, nested case-control,
      ecologic, clinical trial, meta-analysis). RESULTS: Of the 29 studies reviewed on
      cancers of the gastrointestinal tract, all except three found higher serum
      albumin levels to be associated with better survival in multivariate analysis. Of
      the 10 studies reviewed on lung cancer, all excepting one found higher serum
      albumin levels to be associated with better survival. In 6 studies reviewed on
      female cancers and multiple cancers each, lower levels of serum albumin were
      associated with poor survival. Finally, in all 8 studies reviewed on patients
      with other cancer sites, lower levels of serum albumin were associated with poor
      survival. CONCLUSIONS: Pretreatment serum albumin levels provide useful
      prognostic significance in cancer. Accordingly, serum albumin level could be used
      in clinical trials to better define the baseline risk in cancer patients. A
      critical gap for demonstrating causality, however, is the absence of clinical
      trials demonstrating that raising albumin levels by means of intravenous infusion
      or by hyperalimentation decreases the excess risk of mortality in cancer.

PMID- 21176211
TI  - Experiences and barriers to Health-Related Quality of Life following liver
      transplantation: a qualitative analysis of the perspectives of pediatric patients
      and their parents.
AB  - This paper examines health-related quality of life (HRQOL) experiences and
      barriers facing young people who have received a liver transplant (LT). Semi
      structured qualitative interviews were conducted with children and adolescents
      who have undergone LT and their parents. Findings indicate that LT fosters
      substantially improved child and adolescent HRQOL; however, young people also
      experience challenges such as difficulties with medication compliance, self
      management of care routines, physical activity restrictions, and undesirable
      medical procedures. Implications and recommendations for clinical practice and
      research are discussed.

PMID- 21176212
TI  - Angiogenesis is present in experimental autoimmune encephalomyelitis and pro
      angiogenic factors are increased in multiple sclerosis lesions.
AB  - BACKGROUND: Angiogenesis is a common finding in chronic inflammatory diseases;
      however, its role in multiple sclerosis (MS) is unclear. Central nervous system
      lesions from both MS and experimental autoimmune encephalomyelitis (EAE), the
      animal model of MS, contain T cells, macrophages and activated glia, which can
      produce pro-angiogenic factors. Previous EAE studies have demonstrated an
      increase in blood vessels, but differences between the different phases of
      disease have not been reported. Therefore we examined angiogenic promoting
      factors in MS and EAE lesions to determine if there were changes in blood vessel
      density at different stages of EAE. METHODS: In this series of experiments we
      used a combination of vascular casting, VEGF ELISA and immunohistochemistry to
      examine angiogenesis in experimental autoimmune encephalomyelitis (EAE). Using
      immunohistochemistry we also examined chronic active MS lesions for angiogenic
      factors. RESULTS: Vascular casting and histological examination of the spinal
      cord and brain of rats with EAE demonstrated that the density of patent blood
      vessels increased in the lumbar spinal cord during the relapse phase of the
      disease (p < 0.05). We found an increased expression of VEGF by inflammatory
      cells and a decrease in the recently described angiogenesis inhibitor meteorin.
      Examination of chronic active human MS tissues demonstrated glial expression of
      VEGF and glial and blood vessel expression of the pro-angiogenic receptor VEGFR2.
      There was a decreased expression of VEGFR1 in the lesions compared to normal
      white matter. CONCLUSIONS: These findings reveal that angiogenesis is intimately
      involved in the progression of EAE and may have a role in MS.

PMID- 21176213
TI  - Preliminary observations of muscle fibre cross sectional area of flexor digitorum
      brevis in cadaver feet with and without claw toes.
AB  - BACKGROUND: In order to facilitate normal gait, toes require to be in a rectus
      position during the propulsive phase. This requires a correct balance and
      sequence of activity of the intrinsic musculature of the feet. Alteration of this
      balance and sequence may lead to the development of claw toes. Atrophy of the
      lumbricals occurs in the development of claw toes, but it is not known if changes
      occur in any other intrinsic muscles, including flexor digitorum brevis. This
      study set out to investigate whether hypertrophic changes were evident in flexor
      digitorum brevis in feet with claw toes. METHODS: Four cadaver feet were
      investigated, two with rectus toes and two with claw toes. Flexor digitorum
      brevis was removed from each, and seven anatomically significant tissue sections
      from each muscle were routinely processed, cut and stained. One hundred and sixty
      muscle fibre cross sectional areas were measured from each section. RESULTS: The
      mean age of the donors was 81.5 years, and three of the four were female. Results
      showed that the cross sectional area of fibres from feet with claw toes was 417
      MUg2 significantly greater (p < 0.01) than the cross sectional area of fibres
      from feet with rectus toes, which was 263 MUg2. CONCLUSIONS: Although this study
      has several limitations, preliminary observations reveal that flexor digitorum
      brevis muscle fibre cross sectional area is significantly reduced in feet with
      claw toes. This would indicate a relationship between muscle fibre atrophy of
      flexor digitorum brevis and clawing of the lesser toes.

PMID- 21176214
TI  - Herpes simplex virus type 2 seropositivity and relationship status among U.S.
      adults age 20 to 49: a population-based analysis.
AB  - BACKGROUND: U.S. population studies show herpes simplex virus type 2 (HSV-2)
      seroprevalence levelling by approximately age 30, suggesting few new infections
      after that age. It is unclear whether this pattern is driven by greater
      percentages in stable relationships, and to what extent adults who initiate new
      relationships may be at risk of incident HSV-2 infection. METHODS: Survey and
      laboratory data from the 1999-2008 waves of the U.S. National Health and
      Nutrition Examination Survey (NHANES) were combined for 12,862 adults age 20-49.
      Weighted population estimates of self-reported genital herpes, HSV-2
      seroprevalence, and past-year sexual history were calculated, stratified by age,
      sex, race, and relationship status. Multivariable logistic regression was used to
      assess whether relationship status provided additional information in predicting
      HSV-2 over age, race and sex, and whether any such associations could be
      accounted for through differences in lifetime number of sex partners. RESULTS:
      Those who were unpartnered had higher HSV-2 prevalence than those who were
      married/cohabitating. Among unpartnered 45-49 year olds, seroprevalence was 55.3%
      in women and 25.7% in men. Those who were married/cohabitating were more likely
      to have had a past-year sex partner, and less likely to have had two or more
      partners. The effect of age in increasing the odds of HSV-2 was modified by race,
      with higher HSV-2 prevalence among Black Americans established by age 20-24
      years, and the effect of race decreasing from age 30 to 49. Relationship status
      remained an independent predictor of HSV-2 when controlling for age, race, and
      sex among those age 30 to 49; married/cohabitating status was protective for HSV
      2 in this group (OR = 0.69) CONCLUSIONS: Whereas sexually transmitted infections
      are often perceived as issues for young adults and specific high-risk groups, the
      chronic nature of HSV-2 results in accumulation of prevalence with age,
      especially among those not in married/cohabitating relationships. Increased odds
      of HSV-2 with age did not correspond with increases in self-reported genital
      herpes, which remained low. Adults who initiate new relationships should be aware
      of HSV-2 in order to better recognize its symptoms and prevent transmission.

PMID- 21176215
TI  - A population-based case-control study of Selective Serotonin Reuptake Inhibitors
      (SSRIs) and breast cancer: the impact of duration of use, cumulative dose and
      latency.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs), a popular class of
      antidepressants, may increase breast cancer risk by stimulating the secretion of
      prolactin, a potential tumour promoter. We evaluated the effects of duration of
      SSRI use, cumulative dose, and latency on the risk of breast cancer by conducting
      a population-based case-control study utilizing Saskatchewan health databases.
      METHODS: Cases included 1,701 women with primary invasive breast cancer diagnosed
      from 2003 to 2006, and controls consisted of 17,017 women, randomly selected from
      the population registry. Use of SSRIs was compiled using the Saskatchewan
      prescription database. Unconditional logistic regression was conducted to
      evaluate the impact of duration of combined SSRI use (total number of
      prescriptions dispensed), cumulative dose (total dosage received) and timing of
      use (two or more years, two to seven years and more than seven years prior to
      index date) on the risk of breast cancer. RESULTS: Overall, SSRI use was not
      associated with an increased risk of breast cancer regardless of our definition
      of cumulative use (total number of prescriptions dispensed and total dosage). In
      addition, our results indicate that prolonged SSRI use does not have a latent
      effect on breast cancer risk. Also, our findings are not suggestive of an
      increased risk of breast cancer with the use of individual SSRIs. CONCLUSIONS:
      Our study improved upon most previous studies by having a longer follow-up
      period, a larger sample size of long-term SSRI users and consideration of risk
      during specific exposure time windows that take latency into account. Given the
      potential health benefits of using SSRIs, our results suggest that the issue of
      breast cancer risk may no longer be a concern for women requiring long-term
      SSRIs.

PMID- 21176216
TI  - Accounting for multiple comparisons in a genome-wide association study (GWAS).
AB  - BACKGROUND: As we enter an era when testing millions of SNPs in a single gene
      association study will become the standard, consideration of multiple comparisons
      is an essential part of determining statistical significance. Bonferroni
      adjustments can be made but are conservative due to the preponderance of linkage
      disequilibrium (LD) between genetic markers, and permutation testing is not
      always a viable option. Three major classes of corrections have been proposed to
      correct the dependent nature of genetic data in Bonferroni adjustments:
      permutation testing and related alternatives, principal components analysis
      (PCA), and analysis of blocks of LD across the genome. We consider seven
      implementations of these commonly used methods using data from 1514 European
      American participants genotyped for 700,078 SNPs in a GWAS for AIDS. RESULTS: A
      Bonferroni correction using the number of LD blocks found by the three algorithms
      implemented by Haploview resulted in an insufficiently conservative threshold,
      corresponding to a genome-wide significance level of alpha = 0.15 - 0.20. We
      observed a moderate increase in power when using PRESTO, SLIDE, and simpleM when
      compared with traditional Bonferroni methods for population data genotyped on the
      Affymetrix 6.0 platform in European Americans (alpha = 0.05 thresholds between 1
      * 10(-7) and 7 * 10(-8)). CONCLUSIONS: Correcting for the number of LD blocks
      resulted in an anti-conservative Bonferroni adjustment. SLIDE and simpleM are
      particularly useful when using a statistical test not handled in optimized
      permutation testing packages, and genome-wide corrected p-values using SLIDE, are
      much easier to interpret for consumers of GWAS studies.

PMID- 21176217
TI  - Relationship between alcohol use disorders, cortisol concentrations, and cytokine
      levels in patients with sepsis.
AB  - INTRODUCTION: Patients with alcohol use disorders (AUD) are at increased risk of
      developing sepsis and have higher mortality. AUD are associated with higher
      cortisol and anti-inflammatory cytokine profile. Higher cortisol increases risk
      of death in septic patients. The relationship between AUD and cortisol in septic
      patients is unknown. We aimed to study this relationship and postulated that AUD
      would be associated with higher cortisol and anti-inflammatory cytokine profile.
      METHODS: This was a prospective cohort study of 40 medical intensive care unit
      (ICU) patients admitted with sepsis. Cortisol, anti-inflammatory interleukin (IL)
      10, and pro-inflammatory IL1beta, IL6, tumor necrosis factor (TNF) alpha were
      measured. RESULTS: Thirteen (32%) out of 40 patients had AUD. AUD patients had
      higher cortisol by univariate (39 microg/dl versus 24, P = 0.04) and
      multivariable analyses (44 microg/dl versus 23, P = 0.004). By univariate
      analyses, AUD patients had higher IL10 (198 picog/dl versus 47, P = 0.02) and IL6
      (527 picog/ml versus 156, P = 0.048), but similar IL1beta and TNFalpha. By
      multivariable analyses, AUD patients had higher IL10 (182 picog/dl versus 23, P =
      0.049) but similar IL1beta, IL6, and TNFalpha. AUD patients had lower
      IL1beta/IL10 (univariate 0.01 versus 0.10, P = 0.04; multivariable 0.01 versus
      0.03, P = 0.04), lower TNFalpha/IL10 (univariate 0.15 versus 0.52, P = 0.03;
      multivariable 0.11 versus 0.63, P = 0.01), but similar IL6/IL10. CONCLUSIONS: AUD
      are common diagnoses among medical ICU patients with sepsis. Patients with AUD
      have higher cortisol concentrations and have differences in cytokine expression.
      Future studies should seek to determine if these differences may explain the
      higher severity of illness seen in patients with sepsis and AUD. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT00615862.

PMID- 21176218
TI  - Pre-hospital cooling of patients following cardiac arrest is effective using even
      low volumes of cold saline.
AB  - INTRODUCTION: Pre-hospital induction of therapeutic mild hypothermia (TH) may
      reduce post-cardiac arrest brain injury in patients resuscitated from out-of
      hospital cardiac arrest. Most often, it is induced by a rapid intravenous
      administration of as much as 30 ml/kg of cold crystalloids. We decided to assess
      the pre-hospital cooling effectivity of this approach by using a target dose of
      15-20 ml/kg of 4 degrees C cold normal saline in the setting of the physician
      staffed Emergency Medical Service. The safety and impact on the clinical outcome
      have also been analyzed. METHODS: We performed a prospective observational study
      with a retrospective control group. A total of 40 patients were cooled by an
      intravenous administration of 15-20 ml/kg of 4 degrees C cold normal saline
      during transport to the hospital (TH group). The pre-hospital decrease of
      tympanic temperature (TT) was analyzed as the primary endpoint. Patients in the
      control group did not undergo any pre-hospital cooling. RESULTS: In the TH group,
      administration of 12.6 +/- 6.4 ml/kg of 4 degrees C cold normal saline was
      followed by a pre-hospital decrease of TT of 1.4 +/- 0.8 degrees C in 42.8 +/-
      19.6 min (p < 0.001). The most effective cooling was associated with a transport
      time duration of 38-60 min and with an infusion of 17 ml/kg of cold saline. In
      the TH group, a trend toward a reduced need for catecholamines during transport
      was detected (35.0 vs. 52.5%, p = 0.115). There were no differences in
      demographic variables, comorbidities, parameters of the cardiopulmonary
      resuscitation and in other post-resuscitation characteristics. The coupling of
      pre-hospital cooling with subsequent in-hospital TH predicted a favorable
      neurological outcome at hospital discharge (OR 4.1, CI95% 1.1-18.2, p = 0.046).
      CONCLUSIONS: Pre-hospital induction of TH by the rapid intravenous administration
      of cold normal saline has been shown to be efficient even with a lower dose of
      coolant than reported in previous studies. This dose can be associated with a
      favorable impact on circulatory stability early after the return of spontaneous
      circulation and, when coupled with in-hospital continuation of cooling, can
      potentially improve the prognosis of patients. TRIAL REGISTRATION: ClinicalTrials
      (NCT): NCT00915421.

PMID- 21176219
TI  - Breast cancer research output, 1945-2008: a bibliometric and density-equalizing
      analysis.
AB  - NTRODUCTION: Breast cancer is the most common form of cancer among women, with an
      estimated 194,280 new cases diagnosed in the United States in 2009 alone. The
      primary aim of this work was to provide an in-depth evaluation of research yield
      in breast cancer from 1945 to 2008, using large-scale data analysis, the
      employment of bibliometric indicators of production and quality, and density
      equalizing mapping. METHODS: Data were retrieved from the Web of Science (WOS)
      Science Citation Expanded database; this was searched using the Boolean operator,
      'OR', with different terms related to breast cancer, including "breast cancer",
      "mammary ductal carcinoma" and "breast tumour". Data were then extracted from
      each file, transferred to Excel charts and visualised as diagrams. Mapping was
      performed as described by Groneberg-Kloft et al. in 2008. RESULTS: A total of
      180,126 breast cancer-associated items were produced over the study period; these
      had been cited 4,136,224 times. The United States returned the greatest level of
      output (n = 77,101), followed by the UK (n = 18,357) and Germany (n = 12,529).
      International cooperation peaked in 2008, with 3,127 entries produced as a
      result; relationships between the United States and other countries formed the
      basis for the 10 most common forms of bilateral cooperation. Publications from
      nations with high levels of international cooperation were associated with
      greater average citation rates. A total of 4,096 journals published at least one
      item on breast cancer, although the top 50 most prolific titles together
      accounted for over 43% (77,517/180,126) of the total output. CONCLUSIONS: Breast
      cancer-associated research output continues to increase annually. In an era when
      bibliometric indicators are increasingly being employed in performance
      assessment, these findings should provide useful information for those tasked
      with improving that performance.

PMID- 21176221
TI  - Differential fate and functional outcome of lithium chloride primed adult neural
      progenitor cell transplants in a rat model of Huntington disease.
AB  - INTRODUCTION: The ability to predetermine the fate of transplanted neural
      progenitor cells (NPCs) and specifically to direct their maturation has the
      potential to enhance the efficiency of cell-transplantation therapy for
      neurodegenerative disease. We previously demonstrated that transient exposure of
      subventricular zone (SVZ)-derived adult NPCs to lithium chloride during in vitro
      proliferation alters differential fate in vitro and increases the proportion of
      cells expressing neuronal markers while reducing glial progeny. To extend these
      findings, we examined whether in vitro priming of adult SVZ-derived NPCs with
      lithium chloride before transplantation into the quinolinic acid (QA) lesion rat
      model of Huntington disease altered in vivo neuronal differentiation and
      sensorimotor function compared with nonprimed NPC transplants. METHODS: NPCs were
      isolated from the SVZ of the adult rat brain and cultured for 2 weeks. Four days
      before transplantation into the QA-lesioned rat striatum, the cells were labeled
      with BrdU and primed with lithium chloride. The rats underwent regular evaluation
      of forelimb use and sensorimotor neglect to establish functional effects of NPC
      transplantation. Twelve weeks after transplantation, the brains were analyzed
      with immunohistochemistry to compare the differential fate of primed and
      nonprimed NPCs. RESULTS: We observed that in vitro priming of adult NPCs with
      lithium chloride reduced gliogenesis and enhanced the occurrence of DARPP-32
      positive neurons when compared with nonprimed cells 12 weeks after
      transplantation into the QA-lesioned striatum. Lithium chloride priming also
      augmented the formation of efferent projections from newly formed neurons in the
      damaged host striatum to the globus pallidus. This was associated with
      acceleration of sensorimotor function recovery in rats receiving transplants of
      lithium chloride-primed adult NPCs compared with nonprimed transplants.
      CONCLUSIONS: These initial findings indicate that in vitro priming of adult NPCs
      with lithium chloride may augment transplant efficiency and accelerate
      sensorimotor function outcome in vivo.

PMID- 21176220
TI  - Modulation of HIV-1-host interaction: role of the Vpu accessory protein.
AB  - Viral protein U (Vpu) is a type 1 membrane-associated accessory protein that is
      unique to human immunodeficiency virus type 1 (HIV-1) and a subset of related
      simian immunodeficiency virus (SIV). The Vpu protein encoded by HIV-1 is
      associated with two primary functions during the viral life cycle. First, it
      contributes to HIV-1-induced CD4 receptor downregulation by mediating the
      proteasomal degradation of newly synthesized CD4 molecules in the endoplasmic
      reticulum (ER). Second, it enhances the release of progeny virions from infected
      cells by antagonizing Tetherin, an interferon (IFN)-regulated host restriction
      factor that directly cross-links virions on host cell-surface. This review will
      mostly focus on recent advances on the role of Vpu in CD4 downregulation and
      Tetherin antagonism and will discuss how these two functions may have impacted
      primate immunodeficiency virus cross-species transmission and the emergence of
      pandemic strain of HIV-1.

PMID- 21176222
TI  - Differential expression of aldehyde dehydrogenase 1a1 (ALDH1) in normal ovary and
      serous ovarian tumors.
AB  - BACKGROUND: We showed there are specific ALDH1 autoantibodies in ovarian
      autoimmune disease and ovarian cancer, suggesting a role for ALDH1 in ovarian
      pathology. However, there is little information on the ovarian expression of
      ALDH1. Therefore, we compared ALDH1 expression in normal ovary and benign and
      malignant ovarian tumors to determine if ALDH1 expression is altered in ovarian
      cancer. Since there is also recent interest in ALDH1 as a cancer stem cell (CSC)
      marker, we assessed co-expression of ALDH1 with CSC markers in order to determine
      if ALDH1 is a potential CSC marker in ovarian cancer. METHODS: mRNA and protein
      expression were compared in normal human ovary and serous ovarian tumors using
      quantitative Reverse-Transcriptase PCR, Western blot (WB) and semi-quantitative
      immunohistochemistry (IHC). ALDH1 enzyme activity was confirmed in primary
      ovarian cells by flow cytometry (FC) using ALDEFLUOR assay. RESULTS: ALDH1 mRNA
      expression was significantly reduced (p < 0.01; n = 5) in malignant tumors
      compared to normal ovaries and benign tumors. The proportion of ALDH1+ cells was
      significantly lower in malignant tumors (17.1 +/- 7.61%; n = 5) compared to
      normal ovaries (37.4 +/- 5.4%; p < 0.01; n = 5) and benign tumors (31.03 +/-
      6.68%; p < 0.05; n = 5). ALDH1+ cells occurred in the stroma and surface
      epithelium in normal ovary and benign tumors, although surface epithelial
      expression varied more in benign tumors. Localization of ALDH1 was heterogeneous
      in malignant tumor cells and little ALDH1 expression occurred in poorly
      differentiated malignant tumors. In benign tumors the distribution of ALDH1 had
      features of both normal ovary and malignant tumors. ALDH1 protein expression
      assessed by IHC, WB and FC was positively correlated (p < 0.01). ALDH1 did not
      appear to be co-expressed with the CSC markers CD44, CD117 and CD133 by IHC.
      CONCLUSIONS: Total ALDH1 expression is significantly reduced in malignant ovarian
      tumors while it is relatively unchanged in benign tumors compared to normal
      ovary. Thus, ALDH1 expression in the ovary does not appear to be similar to
      breast, lung or colon cancer suggesting possible functional differences in these
      cancers. SIGNIFICANCE: These observations suggest that reduced ALDH1 expression
      is associated with malignant transformation in ovarian cancer and provides a
      basis for further study of the mechanism of ALDH1 in this process.

PMID- 21176223
TI  - Caenorhabditis elegans chromosome arms are anchored to the nuclear membrane via
      discontinuous association with LEM-2.
AB  - BACKGROUND: Although Caenorhabditis elegans was the first multicellular organism
      with a completely sequenced genome, how this genome is arranged within the
      nucleus is not known. RESULTS: We determined the genomic regions associated with
      the nuclear transmembrane protein LEM-2 in mixed-stage C. elegans embryos via
      chromatin immunoprecipitation. Large regions of several megabases on the arms of
      each autosome were associated with LEM-2. The center of each autosome was mostly
      free of such interactions, suggesting that they are largely looped out from the
      nuclear membrane. Only the left end of the X chromosome was associated with the
      nuclear membrane. At a finer scale, the large membrane-associated domains
      consisted of smaller subdomains of LEM-2 associations. These subdomains were
      characterized by high repeat density, low gene density, high levels of H3K27
      trimethylation, and silent genes. The subdomains were punctuated by gaps
      harboring highly active genes. A chromosome arm translocated to a chromosome
      center retained its association with LEM-2, although there was a slight decrease
      in association near the fusion point. CONCLUSIONS: Local DNA or chromatin
      properties are the main determinant of interaction with the nuclear membrane,
      with position along the chromosome making a minor contribution. Genes in small
      gaps between LEM-2 associated regions tend to be highly expressed, suggesting
      that these small gaps are especially amenable to highly efficient transcription.
      Although our data are derived from an amalgamation of cell types in mixed-stage
      embryos, the results suggest a model for the spatial arrangement of C. elegans
      chromosomes within the nucleus.

PMID- 21176224
TI  - A descriptive analysis of a representative sample of pediatric randomized
      controlled trials published in 2007.
AB  - BACKGROUND: Randomized controlled trials (RCTs) are the gold standard for trials
      assessing the effects of therapeutic interventions; therefore it is important to
      understand how they are conducted. Our objectives were to provide an overview of
      a representative sample of pediatric RCTs published in 2007 and assess the
      validity of their results. METHODS: We searched Cochrane Central Register of
      Controlled Trials using a pediatric filter and randomly selected 300 RCTs
      published in 2007. We extracted data on trial characteristics; outcomes;
      methodological quality; reporting; and registration and protocol characteristics.
      Trial registration and protocol availability were determined for each study based
      on the publication, an Internet search and an author survey. RESULTS: Most
      studies (83%) were efficacy trials, 40% evaluated drugs, and 30% were placebo
      controlled. Primary outcomes were specified in 41%; 43% reported on adverse
      events. At least one statistically significant outcome was reported in 77% of
      trials; 63% favored the treatment group. Trial registration was declared in 12%
      of publications and 23% were found through an Internet search. Risk of bias (ROB)
      was high in 59% of trials, unclear in 33%, and low in 8%. Registered trials were
      more likely to have low ROB than non-registered trials (16% vs. 5%; p = 0.008).
      Effect sizes tended to be larger for trials at high vs. low ROB (0.28, 95% CI
      0.21,0.35 vs. 0.16, 95% CI 0.07,0.25). Among survey respondents (50% response
      rate), the most common reason for trial registration was a publication
      requirement and for non-registration, a lack of familiarity with the process.
      CONCLUSIONS: More than half of this random sample of pediatric RCTs published in
      2007 was at high ROB and three quarters of trials were not registered. There is
      an urgent need to improve the design, conduct, and reporting of child health
      research.

PMID- 21176225
TI  - MBAT: a scalable informatics system for unifying digital atlasing workflows.
AB  - BACKGROUND: Digital atlases provide a common semantic and spatial coordinate
      system that can be leveraged to compare, contrast, and correlate data from
      disparate sources. As the quality and amount of biological data continues to
      advance and grow, searching, referencing, and comparing this data with a
      researcher's own data is essential. However, the integration process is
      cumbersome and time-consuming due to misaligned data, implicitly defined
      associations, and incompatible data sources. This work addressing these
      challenges by providing a unified and adaptable environment to accelerate the
      workflow to gather, align, and analyze the data. RESULTS: The MouseBIRN Atlasing
      Toolkit (MBAT) project was developed as a cross-platform, free open-source
      application that unifies and accelerates the digital atlas workflow. A tiered,
      plug-in architecture was designed for the neuroinformatics and genomics goals of
      the project to provide a modular and extensible design. MBAT provides the ability
      to use a single query to search and retrieve data from multiple data sources,
      align image data using the user's preferred registration method, composite data
      from multiple sources in a common space, and link relevant informatics
      information to the current view of the data or atlas. The workspaces leverage
      tool plug-ins to extend and allow future extensions of the basic workspace
      functionality. A wide variety of tool plug-ins were developed that integrate pre
      existing as well as newly created technology into each workspace. Novel atlasing
      features were also developed, such as supporting multiple label sets, dynamic
      selection and grouping of labels, and synchronized, context-driven display of
      ontological data. CONCLUSIONS: MBAT empowers researchers to discover correlations
      among disparate data by providing a unified environment for bringing together
      distributed reference resources, a user's image data, and biological atlases into
      the same spatial or semantic context. Through its extensible tiered plug-in
      architecture, MBAT allows researchers to customize all platform components to
      quickly achieve personalized workflows.

PMID- 21176226
TI  - Global health competencies and approaches in medical education: a literature
      review.
AB  - BACKGROUND: Physicians today are increasingly faced with healthcare challenges
      that require an understanding of global health trends and practices, yet little
      is known about what constitutes appropriate global health training. METHODS: A
      literature review was undertaken to identify competencies and educational
      approaches for teaching global health in medical schools. RESULTS: Using a pre
      defined search strategy, 32 articles were identified; 11 articles describing 15
      global health competencies for undergraduate medical training were found. The
      most frequently mentioned competencies included an understanding of: the global
      burden of disease, travel medicine, healthcare disparities between countries,
      immigrant health, primary care within diverse cultural settings and skills to
      better interface with different populations, cultures and healthcare systems.
      However, no consensus on global health competencies for medical students was
      apparent. Didactics and experiential learning were the most common educational
      methods used, mentioned in 12 and 13 articles respectively. Of the 11 articles
      discussing competencies, 8 linked competencies directly to educational
      approaches. CONCLUSIONS: This review highlights the imperative to document global
      health educational competencies and approaches used in medical schools and the
      need to facilitate greater consensus amongst medical educators on appropriate
      global health training for future physicians.

PMID- 21176227
TI  - Cell cyclins: triggering elements of cancer or not?
AB  - Cyclins are indispensable elements of the cell cycle and derangement of their
      function can lead to cancer formation. Recent studies have also revealed more
      mechanisms through which cyclins can express their oncogenic potential. This
      review focuses on the aberrant expression of G1/S cyclins and especially cyclin D
      and cyclin E; the pathways through which they lead to tumour formation and their
      involvement in different types of cancer. These elements indicate the mechanisms
      that could act as targets for cancer therapy.

PMID- 21176228
TI  - Cost comparison of microscopy vs. empiric treatment for malaria in Southwestern
      Nigeria: a prospective study.
AB  - BACKGROUND: Presumptive treatment for malaria is common in resource-limited
      settings, yet controversial given the imprecision of clinical diagnosis. The
      researchers compared costs of diagnosis and drugs for two strategies: (1)
      empirical treatment of malaria via clinical diagnosis; and (2) empirical
      diagnosis followed by treatment only with Giemsa smear confirmation. METHODS:
      Patients with a diagnosis of clinical malaria were recruited from a
      mission/university teaching hospital in southwestern Nigeria. The patients
      underwent free Giemsa thick (diagnosis) and thin (differentiation) smears, but
      paid for all anti-malarial drugs. Clinical diagnosis was made on clinicians'
      judgments based on symptoms, including fever, diarrhoea, headache, and body
      aches. The paediatric regimen was artesunate (6-9 tablets of 3 mg/kg on day one
      and 1.5 mg/kg for the next four days) plus amodiaquine (10 mg/kg day 1-2 and 5
      mg/kg on day three in suspension). Adults were given two treatment options:
      option one (four and one-half 50 mg artesunate tablets on day one and nine
      tablets for the next four days, plus three 500 mg sulphadoxine/25 mg
      pyrimethamine tablets) and option two (same artesunate regimen plus nine 200 mg
      tablets of amodiaquine at 10 mg/kg day 1-2 and 5 mg/kg on day three). The
      researchers calculated the costs of smears/drugs from standard hospital charges.
      RESULTS: Doctors diagnosed 304 patients (170 adults ages >16 years and 134
      pediatric) with clinical malaria, prescribing antimalarial drugs to all. Giemsa
      thick smears were positive in 115/304 (38%). The typical patient cost for a
      Giemsa smear was 550 Naira (US$3.74 in 2009). For children, the cost of testing
      all, but treating only Giemsa positives was N888 ($6.04)/child; the cost of
      empiric treatment of all who were clinically diagnosed was lower, N660
      ($4.49)/child. For adults, the cost of testing all, but treating only Giemsa
      positives was N711 ($4.84)/adult for treatment option one (artesunate and
      sulphadoxine/pyrimethamine) and N730 ($4.97)/adult for option two (artesunate and
      amodiaquine). This contrasts to lower costs of empiric treatment for both options
      one (N610 = $4.14/adult) and two (N680=$4.63/adult). CONCLUSIONS: Empiric
      treatment of all suspected cases of malaria was cheaper (at the end of the dry to
      the beginning of the rainy season) than only treating those who had microscopy
      confirmed diagnoses of malaria, even though the majority of patients suspected to
      have malaria were negative via microscopy. One can acknowledge that giving many
      malaria-uninfected Nigerians anti-malarial drugs is undesirable for both their
      personal health and fears of drug resistance with overuse. Therefore, funding of
      rapid diagnostic tests whose performance exceeds the Giemsa smear is needed to
      achieve an ideal of diagnostic confirmation before treatment.

PMID- 21176229
TI  - Involving users in the design of a randomised controlled trial of an intervention
      to promote early presentation in breast cancer: qualitative study.
AB  - BACKGROUND: The purpose of this study was to explore women's views of the design
      of a large pragmatic cost-effectiveness randomised controlled trial of the policy
      of offering a health professional-delivered intervention to promote early
      presentation with breast symptoms in older women and thereby improve survival,
      with a view to informing protocol development. The trial will recruit over
      100,000 healthy women aged 67+, and outcome data will be collected on those who
      develop breast cancer. The scale of the trial and the need for long-term follow
      up presented a number of design challenges in relation to obtaining consent,
      ascertaining and contacting participants who developed breast cancer, and
      collecting outcome data. METHODS: Qualitative study involving 69 women
      participating in 7 focus groups and 17 in-depth interviews. 15 women had a
      previous diagnosis of breast cancer and 54 did not. RESULTS: The women held
      strong views and had a good understanding of the rationale of the design of
      clinical trials. The women recognised that in a very large trial with long-term
      follow-up it was necessary to incorporate design features to make the trial
      feasible and efficient. Most strikingly, they supported the idea of opt-out
      consent and identifying women with breast cancer using routine datasets.
      CONCLUSIONS: This model of user involvement engaged women well with the design
      challenges of the trial and led to improvements to the protocol. The study
      strengthens the case for user involvement, in particular through focus groups and
      in-depth interviews, in the design of trials.

PMID- 21176230
TI  - Awareness and knowledge of HPV, cervical cancer, and vaccines in young women
      after first delivery in Sao Paulo, Brazil--a cross-sectional study.
AB  - BACKGROUND: The success of HPV vaccination programs will require awareness
      regarding HPV associated diseases and the benefits of HPV vaccination for the
      general population. The aim of this study was to assess the level of awareness
      and knowledge of human papillomavirus (HPV) infection, cervical cancer
      prevention, vaccines, and factors associated with HPV awareness among young women
      after birth of the first child. METHODS: This analysis is part of a cross
      sectional study carried out at Hospital Maternidade Leonor Mendes de Barros, a
      large public maternity hospital in Sao Paulo. Primiparous women (15-24 years) who
      gave birth in that maternity hospital were included. A questionnaire that
      included questions concerning knowledge of HPV, cervical cancer, and vaccines was
      applied. To estimate the association of HPV awareness with selected factors,
      prevalence ratios (PR) were estimated using a generalized linear model (GLM).
      RESULTS: Three hundred and one primiparous women were included; 37% of them
      reported that they "had ever heard about HPV", but only 19% and 7%, respectively,
      knew that HPV is a sexually transmitted infection (STI) and that it can cause
      cervical cancer. Seventy-four percent of interviewees mentioned the preventive
      character of vaccines and all participants affirmed that they would accept HPV
      vaccination after delivery. In the multivariate analysis, only increasing age (P
      for trend = 0.021) and previous STI (P < 0.001) were factors independently
      associated with HPV awareness ("had ever heard about HPV"). CONCLUSIONS: This
      survey indicated that knowledge about the association between HPV and cervical
      cancer among primiparous young women is low. Therefore, these young low-income
      primiparous women could benefit greatly from educational interventions to
      encourage primary and secondary cervical cancer prevention programs.

PMID- 21176231
TI  - Evaluation of adverse effects in tamoxifen exposed healthy female dogs.
AB  - BACKGROUND: Mammary tumors are among the most frequent neoplasms in female dogs,
      but the strategies employed in animal treatment are limited. In human medicine,
      hormone manipulation is used in cancer therapy. Tamoxifen citrate is a selective
      inhibitor of oestrogen receptors and exerts a potent anti-oestrogen effect on the
      mammary gland. The aim of this study was to evaluate the adverse effects when
      exposing healthy female dogs to tamoxifen. METHODS: Tamoxifen was administered
      for 120 days at a dose of 0.5 or 0.8 mg/kg/day to either intact or spayed female
      dogs. The effects were assessed through clinical examination, haematology, serum
      biochemistry, ophthalmology and bone marrow aspirate examination.
      Ovariohysterectomy was performed and the uterus examined by histopathology.
      RESULTS: Vulva oedema and purulent vaginal discharge developed with 10 days of
      tamoxifen exposure in all groups. Pyometra was diagnosed after around 90 days of
      exposure in intact females with frequencies increasing during the following 30
      days of exposure. Up to 50% of dogs within the groups developed retinitis but
      none of the dogs had signs of reduced visual acuity. The prevalence of retinitis
      in each group was similar after 120 days of exposure. Haematological, biochemical
      and bone marrow changes were not observed. Due to the high risk of developing
      pyometra after prolonged exposure to tamoxifen, only spayed animals should be
      given this medication. CONCLUSIONS: A dose of 0.8 mg tamoxifen/kg body weight/day
      is recommended when treating tamoxifen-responsive canine mammary tumors. Due to
      the high risk of developing pyometra, ovariohysterectomy is recommended.

PMID- 21176232
TI  - Outcome and clinical changes in patients 3, 6, 12 months after a severe or major
      hand injury--can sense of coherence be an indicator for rehabilitation focus?
AB  - BACKGROUND: Our objective was to explore outcome and clinical changes in hand
      function, satisfaction in daily occupations, sleep disturbances, health and
      quality of life in consecutive patients after a severe or major hand injury. Our
      objective was also to investigate possible differences between groups according
      to severity of injury, presence of peripheral nerve injury and the patients'
      sense of coherence. METHODS: A postal questionnaire, including demographic data,
      disabilities of the arm, shoulder and hand (DASH), QoL (SF-36), EuroQol (EQ-5D
      VAS), hand function (VAS), satisfaction in daily occupation (SDO), was sent out
      3, 6 and 12 months after injury to 45 consecutive patients with a severe or major
      hand injury. Sense of coherence (SOC) was evaluated at 6 months. For the
      descriptive study, non-parametric tests were used since almost all results were
      measured with ordinal scales, the study sample was small, and most variables not
      normally distributed. RESULTS: Almost all self-assessed aspects of hand function,
      satisfaction in daily occupations, health (DASH), and physical QoL (SF-36)
      improved statistically for the whole group over time. Large clinical improvement
      was seen for physical QoL and health, while a low or no improvement was observed
      for mental QoL, and cold sensitivity. Few differences were found between
      participants with a severe or major of hand injury or with or without a major
      nerve injury. No significant differences in demographic data were observed
      between participants with high or low SOC, but participants with low SOC showed
      significantly lower satisfaction in daily occupations, higher DASH scores, lower
      mental QoL, more sleep disturbances, and bodily pain. Correlation was found
      between SOC, and QoL, health and satisfaction in daily occupations. CONCLUSIONS:
      SOC had a significant influence on patients with a severe or major traumatic hand
      injury. Patients with lower SOC would probably benefit from extra support and
      help to master their daily life, indicating that sense of coherence is an
      indicator for future rehabilitation focus.

PMID- 21176233
TI  - Web-based alcohol screening and brief intervention for Maori and non-Maori: the
      New Zealand e-SBINZ trials.
AB  - BACKGROUND: Hazardous alcohol consumption is a leading modifiable cause of
      mortality and morbidity among young people. Screening and brief intervention
      (SBI) is a key strategy to reduce alcohol-related harm in the community, and web
      based approaches (e-SBI) have advantages over practitioner-delivered approaches,
      being cheaper, more acceptable, administrable remotely and infinitely scalable.
      An efficacy trial in a university population showed a 10-minute intervention
      could reduce drinking by 11% for 6 months or more among 17-24 year-old
      undergraduate hazardous drinkers. The e-SBINZ study is designed to examine the
      effectiveness of e-SBI across a range of universities and among Maori and non
      Maori students in New Zealand. METHODS/DESIGN: The e-SBINZ study comprises two
      parallel, double blind, multi-site, individually randomised controlled trials.
      This paper outlines the background and design of the trial, which is recruiting
      17-24 year-old students from seven of New Zealand's eight universities. Maori and
      non-Maori students are being sampled separately and are invited by e-mail to
      complete a web questionnaire including the AUDIT-C. Those who score >4 will be
      randomly allocated to no further contact until follow-up (control) or to
      assessment and personalised feedback (intervention) via computer. Follow-up
      assessment will occur 5 months later in second semester. Recruitment, consent,
      randomisation, intervention and follow-up are all online. Primary outcomes are
      (i) total alcohol consumption, (ii) frequency of drinking, (iii) amount consumed
      per typical drinking occasion, (iv) the proportions exceeding medical guidelines
      for acute and chronic harm, and (v) scores on an academic problems scale.
      DISCUSSION: The trial will provide information on the effectiveness of e-SBI in
      reducing hazardous alcohol consumption across diverse university student
      populations with separate effect estimates for Maori and non-Maori students.
      TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR)
      ACTRN12610000279022.

PMID- 21176234
TI  - Association of ghrelin and leptin with reproductive hormones in constitutional
      delay of growth and puberty.
AB  - BACKGROUND: Constitutional delay of growth and puberty (CDGP) is a variation of
      the onset and timing of pubertal development without a defined endocrine
      abnormality. Recently published studies indicate that leptin and ghrelin play a
      role in puberty initiation and progress. They have been implicated in regulation
      of GnRH secretion, with ghrelin having inhibitory and leptin, facilitatory
      effects. We hypothesized that elevated ghrelin and reduced leptin concentrations
      could be implicated in altering the tempo of puberty in adolescents with CDGP. So
      in the current study we evaluate variations in leptin and ghrelin levels in
      adolescent boys with CDGP, the relationships between both hormones and
      reproductive hormones including LH, FSH and testosterone were also evaluated.
      METHODS: The study enrolled 23 adolescent boys with CDGP and 20 healthy controls
      matched for age and sex. Weight, height, BMI, testicular volume, bone age, bone
      age delay, serum FSH, LH, testosterone, leptin and ghrelin were assessed.
      RESULTS: Adolescent boys with CDGP had significantly lower leptin and higher
      ghrelin than normal controls. Leptin was positively correlated with BMI, bone
      age, testicular volume, FSH, LH and testosterone and negatively correlated with
      delayed bone age and ghrelin. Ghrelin was negatively correlated with BMI, bone
      age, testicular volume, FSH, LH and testosterone. With multiple regression
      analysis BMI, FSH, LH, testosterone and ghrelin remained independently correlated
      with leptin while BMI, LH and testosterone remained independently correlated with
      ghrelin. CONCLUSION: Elevated serum ghrelin and decreased leptin concentrations
      and their associations with reproductive hormones may explain the sexual
      immaturity in adolescent boys with CDGP.

PMID- 21176235
TI  - Rapid Leptospira identification by direct sequencing of the diagnostic PCR
      products in New Caledonia.
AB  - BACKGROUND: Most of the current knowledge of leptospirosis epidemiology
      originates from serological results obtained with the reference Microscopic
      Agglutination Test (MAT). However, inconsistencies and weaknesses of this
      diagnostic technique are evident. A growing use of PCR has improved the early
      diagnosis of leptospirosis but a drawback is that it cannot provide information
      on the infecting Leptospira strain which provides important epidemiologic data.
      Our work is aimed at evaluating if the sequence polymorphism of diagnostic PCR
      products could be used to identify the infecting Leptospira strains in the New
      Caledonian environment. RESULTS: Both the lfb1 and secY diagnostic PCR products
      displayed a sequence polymorphism that could prove useful in presumptively
      identifying the infecting leptospire. Using both this polymorphism and MLST
      results with New Caledonian isolates and clinical samples, we confirmed the
      epidemiological relevance of the sequence-based identification of Leptospira
      strains. Additionally, we identified one cluster of L. interrogans that contained
      no reference strain and one cluster of L. borgpetersenii found only in the
      introduced Rusa deer Cervus timorensis russa that is its probable reservoir.
      CONCLUSIONS: The sequence polymorphism of diagnostic PCR products proved useful
      in presumptively identifying the infecting Leptospira strains. This could
      contribute to a better understanding of leptospirosis epidemiology by providing
      epidemiological information that cannot be directly attained from the use of PCR
      as an early diagnostic test for leptospirosis.

PMID- 21176236
TI  - Soluble CD40 ligand-activated human peripheral B cells as surrogated antigen
      presenting cells: A preliminary approach for anti-HBV immunotherapy.
AB  - BACKGROUND: We aimed to clarify whether soluble CD40 ligand (sCD40L) activated B
      cells may be loaded with HBcAg18-27 peptide and served as antigen-producing cells
      (APCs) to induce HBV-specific cytolytic T lymphocytes (CTLs). RESULTS: Human B
      cells could be cultured in the presence of sCD40L up to 54 days, and the
      proportion of B cells in the S phase increased from 0% to 8.34% in the culture.
      The expression of CD80, CD86, major histocompatibility complex (MHC) classes I
      and II molecules on the sCD40L-activated B cell was significantly increased after
      long-time culture. Cytometry and fluorescence microscopy showed that more than
      98% sCD40L-activated B cells were loaded by the HBcAg peptide. Furthermore, the
      peptide-pulsed activated B cells could induce HBcAg18-27 specific CTLs.
      CONCLUSIONS: Our results demonstrate that sCD40L-activated B cells may function
      as APCs and induce HBV-specific CTLs.

PMID- 21176237
TI  - Translating tumor biology into personalized treatment planning: analytical
      performance characteristics of the Oncotype DX Colon Cancer Assay.
AB  - BACKGROUND: The Oncotype DX Colon Cancer Assay is a new diagnostic test for
      determining the likelihood of recurrence in stage II colon cancer patients after
      surgical resection using fixed paraffin embedded (FPE) primary colon tumor
      tissue. Like the Oncotype DX Breast Cancer Assay, this is a high complexity,
      multi-analyte, reverse transcription (RT) polymerase chain reaction (PCR) assay
      that measures the expression levels of specific cancer-related genes. By
      capturing the biology underlying each patient's tumor, the Oncotype DX Colon
      Cancer Assay provides a Recurrence Score (RS) that reflects an individualized
      risk of disease recurrence. Here we describe its analytical performance using pre
      determined performance criteria, which is a critical component of molecular
      diagnostic test validation. RESULTS: All analytical measurements met pre
      specified performance criteria. PCR amplification efficiency for all 12 assays
      was high, ranging from 96% to 107%, while linearity was demonstrated over an 11
      log2 concentration range for all assays. Based on estimated components of
      variance for FPE RNA pools, analytical reproducibility and precision demonstrated
      low SDs for individual genes (0.16 to 0.32 CTs), gene groups (<= 0.05
      normalized/aggregate CTs) and RS (<= 1.38 RS units). CONCLUSIONS: Analytical
      performance characteristics shown here for both individual genes and gene groups
      in the Oncotype DX Colon Cancer Assay demonstrate consistent translation of
      specific biology of individual tumors into clinically useful diagnostic
      information. The results of these studies illustrate how the analytical
      capability of the Oncotype DX Colon Cancer Assay has enabled clinical validation
      of a test to determine individualized recurrence risk after colon cancer surgery.

PMID- 21176238
TI  - MicroRNAs involved in neoplastic transformation of liver cancer stem cells.
AB  - BACKGROUND: The existence of cancer stem cells in hepatocellular carcinoma (HCC)
      has been verified by characterizing side population (SP) cells based on efflux of
      Hoechst 33342 dye from stem cells. Recent advances in microRNA (miRNA) biology
      have revealed that miRNAs play an important role in embryonic development and
      tumorigenesis. However, it is still unclear which miRNAs participate in the
      neoplastic transformation of liver cancer stem cells (LCSCs) during
      hepatocarcinogenesis. METHODS: To identify the unique set of miRNAs
      differentially regulated in LCSCs, we applied SP sorting to primary cultures of
      F344 rat HCC cancer cells treated with diethylnitrosamine (DEN) and normal
      syngenic fetal liver cells, and the stem-like characteristics of SP cells were
      verified through detecting expression of CD90.1, AFP and CK-7. Global miRNA
      expression profiles of two groups of SP cells were screened through microarray
      platform. RESULTS: A total of 68 miRNAs, including miR-10b, miR-21, miR-470*, miR
      34c-3p, and let-7i*, were identified as overexpressed in SP of HCC cells compared
      to fetal liver cells. Ten miRNAs were underexpressed, including miR-200a* and miR
      148b*. These miRNAs were validated using stem-loop real-time reverse
      transcriptase polymerase chain reaction (RT-PCR). CONCLUSIONS: Our results
      suggest that LCSCs may have a distinct miRNA expression fingerprint during
      hepatocarcinogenesis. Dissecting these relationships will provide a new
      understanding of the function of miRNA in the process of neoplastic
      transformation of LCSCs.

PMID- 21176239
TI  - Ultrasound-targeted microbubble destruction mediated herpes simplex virus
      thymidine kinase gene treats hepatoma in mice.
AB  - OBJECTIVE: The purpose of the study was to explore the anti-tumor effect of
      ultrasound -targeted microbubble destruction mediated herpes simplex virus
      thymidine kinase (HSV-TK) suicide gene system on mice hepatoma. METHODS: Forty
      mice were randomly divided into four groups after the models of subcutaneous
      transplantation tumors were established: (1) PBS; (2) HSV-TK (3) HSV-TK+
      ultrasound (HSV-TK+US); (4) HSV-TK+ultrasound+microbubbles (HSV-TK+US+MB). The TK
      protein expression in liver cancer was detected by western-blot. Applying TUNEL
      staining detected tumor cell apoptosis. At last, the inhibition rates and
      survival time of the animals were compared among all groups. RESULTS: The TK
      protein expression of HSV-TK+MB+US group in tumor-bearing mice tissues were
      significantly higher than those in other groups. The tumor inhibitory effect of
      ultrasound-targeted microbubble destruction mediated HSV-TK on mice
      transplantable tumor was significantly higher than those in other groups (p <
      0.05), and can significantly improve the survival time of tumor-bearing mice.
      CONCLUSION: Ultrasound-targeted microbubble destruction can effectively transfect
      HSV-TK gene into target tissues and play a significant inhibition effect on
      tumors, which provides a new strategy for gene therapy in liver cancer.

PMID- 21176240
TI  - A novel protein-coding ORF72.2 gene was identified from Marek's disease virus
      strain CVI988.
AB  - Marek's disease is a highly contagious disease of poultry characterized by rapid
      on set of T-cell lymphomas, which is caused by Marek's disease virus (MDV), but
      its pathogenic mechanism is still not very clear. Recently, some new progress
      were achieved in molecular character of MDV. Along with the genomic sequencing of
      MDV serotype 1, some novel open reading frames (ORFs) were predicted, and ORF72.2
      was one of them which have no homologues in other MDV serotypes or in other
      alphaherpesvirus. In the study, ORF72.2 was firstly identified as a protein
      coding gene by the method of reverse transcription polymerase chain reaction (RT
      PCR), western blotting and indirect immunofluorescence assay. This study paved
      the way to conduct further studies to determine whether ORF72.2 plays a role in
      MDV replication and pathogenicity.

PMID- 21176241
TI  - Vitamin D status among adults in the Aegean region of Turkey.
AB  - BACKGROUND: Vitamin D is a lipid-soluble hormone found in certain foods and
      synthesized from precursors in the skin when exposed to ultraviolet light.
      Vitamin D plays a critical role in bone metabolism and many cellular and
      immunological processes and low levels have been associated with several chronic
      and infectious diseases. Vitamin D status is assessed by measuring the
      concentration of serum 25-hydroxyvitamin D [25(OH)D]. Vitamin D deficiency is
      reported to be common worldwide, but little has been reported about the vitamin D
      status of adults in Turkey. In this cross-sectional study, we determined the
      prevalence of 25(OH)D deficiency in adults residing in a city in the Aegean
      region of Turkey. METHODS: A survey was conducted on a representative sample of
      adults over 20 years old in a non-coastal city at the end of the winter season.
      Of the 209 households selected by random sampling, 8.6% (n = 18) were unoccupied
      and 21.5% (n = 45) refused to participate. Blood samples were taken and questions
      about medical history, vitamin supplementation, sunlight exposure, and dietary
      calcium and vitamin D intake were asked in face-to-face interviews of 391 adults
      living in the remaining households. RESULTS: The mean serum 25(OH)D concentration
      was 16.9 +/- 13.09 ng/mL, with 74.9% of the subjects having 25(OH)D deficiency
      (<20 ng/mL), 13.8% having insufficiency (20-29.99 ng/mL), and 11.3% of the
      subjects having sufficient 25(OH)D (>= 30 ng/mL) levels. 25(OH)D deficiency was
      more common among females (78.7%) than males (66.4%, p < 0.05). CONCLUSION:
      Adults living in an urban, non-coastal setting in Turkey have a high prevalence
      of vitamin D deficiency.

PMID- 21176242
TI  - Is staying overnight in a farming hut a risk factor for malaria infection in a
      setting with insecticide-treated bed nets in rural Laos?
AB  - BACKGROUND: Overnight stays in farming huts are known to pose a risk of malaria
      infection. However, studies reporting the risk were conducted in the settings of
      poor net coverage. This study sought to assess whether an overnight stay in a
      farming hut is associated with an increased risk of malaria infection if
      insecticide-treated bed nets (ITNs) are properly used. METHODS: A pair of cross
      sectional surveys was carried out in the Lamarm district of Sekong province,
      Laos, in March (dry season) and August (rainy season) in 2008. Questionnaire
      based interviews and blood examinations were conducted with farmers and their
      household members from three randomly selected villages in March (127 households,
      891 people) and August (128 households, 919 people). Logistic regression
      analysis, adjusted for potential confounding factors, was used to assess the
      association between malaria infection status and frequency of overnight stays for
      the two weeks prior to the study in both the seasons. RESULTS: In March, 13.7% of
      participants reported staying overnight in a farming hut at least once in the
      previous two weeks. The percentage increased to 74.6% in August. Not only adults
      but also young children stayed overnight as often as adults. The use of an ITN
      the preceding night was common both in farming huts (66.3% in March, 95.2% in
      August), and in main residences (85.8% in March, 92.5% in August). Logistic
      regression analysis showed no statistical association between malaria infection
      status and frequency of overnight stays in farming huts in either study period.
      However, people sharing one family type net with five people or more were
      significantly more likely to have malaria than those sharing a net with up to two
      people in the dry season. CONCLUSIONS: This study showed that staying overnight
      in farming huts was not associated with an increased risk of malaria infection in
      the setting where ITNs were widely used in farming huts. It suggests that malaria
      infection during overnight stays in farming huts might be preventable if ITNs are
      properly used in rural Laos.

PMID- 21176243
TI  - Meta-analysis of thyroidectomy with ultrasonic dissector versus conventional
      clamp and tie.
AB  - BACKGROUND: We conducted a systematic review to evaluate the role of Ultrasonic
      dissector (UAS) versus conventional clamp and tie in thyroidectomy. MATERIALS AND
      METHODS: We searched for all published RCT in into electronic databases. To be
      included in the analysis, the studies had to compare thyroidectomy with UAS
      versus conventional vessel ligation and tight (conventional technique = CT). The
      following outcomes were used to compare the total thyroidectomy group with UAS
      versus CT group: operative duration, operative blood loss, overall drainage
      volume during the first 24 hours, transiet laryngeal nerve palsy, permanent
      laryngeal nerve palsy, transiet hypocalcaemia and permanent hypocalcaemia.
      RESULTS: There are currently 7 RCT on this issue to compare thyroidectomy with
      UAS versus CT. From the analysis of these studies it was possible to confront 608
      cases: 303 undergoing to thyroidectomy with UAS versus 305 that were treated with
      CT. Actually, it was shown a relevant advantage of cost-effectiveness in patients
      treated with UAS; there is a statistically significant reduction of the operative
      duration (weighted mean difference [WMD], -18.74 minutes; 95% confidence interval
      [CI], (-26.97 to -10.52 minutes) (P = 0.00001), intraoperative blood loss (WMD, 
      60.10 mL; 95% CI, -117.04 to 3.16 mL) (P = 0.04) and overall drainage volume
      (WMD, -35.30 mL; 95% CI, -49.24 to 21.36 mL) (P = 0.00001) in the patients
      underwent thyroidectomy with UAS. Although the analysis showed that the patients
      who were treated with USA presented more favourable results in incidence of post
      operative complications (transient laryngeal nerve palsy: P = 0.11; permanent
      laryngeal nerve palsy: not estimable; transient hypocalcaemia: P = 0.24;
      permanent hypocalcaemia: P = 0.45), these data didn't present statistical
      relevance. CONCLUSION: This meta-analysis shown a relevant advantage only in
      terms of cost-effectiveness in patients treated with UAS; it is subsequent to
      statistically significant reduction of operation duration, intraoperative blood
      loss and of overall drainage volume during the first 24 hours. Although the
      analysis showed that the patients who were treated with UAS presented more
      favourable results in incidence of post-operative complications (transiet
      laryngeal nerve palsy; transiet hypocalcaemia and permanent hypocalcaemia), these
      data didn't present statistical relevance.

PMID- 21176244
TI  - Gene transfer: anything goes in plant mitochondria.
AB  - Parasitic plants and their hosts have proven remarkably adept at exchanging
      fragments of mitochondrial DNA. Two recent studies provide important mechanistic
      insights into the pattern, process and consequences of horizontal gene transfer,
      demonstrating that genes can be transferred in large chunks and that gene
      conversion between foreign and native genes leads to intragenic mosaicism. A
      model involving duplicative horizontal gene transfer and differential gene
      conversion is proposed as a hitherto unrecognized source of genetic diversity.

PMID- 21176245
TI  - Zebrafish models of the immune response: taking it on the ChIn.
AB  - The zebrafish is proving to be an extremely versatile new experimental model for
      unraveling the mysteries of innate immunity and has considerable promise as a
      system for the identification of novel modulators of this crucial biological
      process. A rate-limiting factor, however, is the mechanical stimulus required to
      induce the inflammatory response. A new chemically induced inflammation assay
      ('ChIn' assay) published in BMC Biology obviates this requirement and seems set
      to accelerate progress in the field.

PMID- 21176247
TI  - [Exclusion of deep-vein thrombosis and pulmonary embolism using clinical decision
      rules and D-dimer tests].
AB  - Clinical diagnosis of a venous thromboembolism (VTE) is often difficult because
      the symptoms of this disorder are diverse and unspecified. The combination of a
      low probability clinical decision rule and an unremarkable D-dimer test is a safe
      way to exclude the presence of a VTE. Clinical decision rules for the diagnosis
      of a deep-vein thrombosis are available for primary and secondary care and
      clinical decision rules for the diagnosis of a pulmonary embolism is available
      for secondary care. Various D-dimer tests are available that differ with regard
      to sensitivity, specificity and duration of the measurement. During pregnancy and
      puerperium using a clinical decision rule and a D-dimer test is inadequate:
      additional radiologic investigation is always indicated in this situation. The
      diagnostic value of the D-dimer test during suspected recurrence of a VTE is yet
      to be determined.

PMID- 21176248
TI  - [Antenatal screening in the Netherlands for HIV, hepatitis B and syphilis is
      effective].
AB  - OBJECTIVE: Evaluation of the effectiveness of antenatal screening in the
      Netherlands for HIV, hepatitis B virus (HBV) and syphilis, in preventing mother
      to-child transmission. DESIGN: Descriptive. METHODS: The results of antenatal
      screening in the period 2006-2008 were compared with data from pregnant women and
      newborns from other data sources. RESULTS: Each year, around 185,000 pregnant
      women were screened for HIV, HBV and syphilis. Refusal rates for the screening
      tests were low, and were highest (0.2%) for HIV. Prior to the introduction of
      screening, 5-10 children were born with HIV annually. After the introduction of
      screening in 2004, only 4 children were born with HIV (an average of 1 per year).
      Two of these mothers had become pregnant prior to 2004; the third mother was HIV
      negative at screening and probably became infected after screening; the fourth
      mother's background was unknown. Congenital syphilis was diagnosed in fewer than
      5 newborns annually and 5 children were infected with HBV. In 3 of these the
      mothers were HBeAg positive (a marker for high infectivity). We estimated that 5
      10 HIV, 50-75 HBV and 10 syphilis cases in newborns had been prevented annually
      as a result of screening. CONCLUSION: The screening programme was effective in
      detecting HIV, HBV and syphilis in pregnant women and in preventing transmission
      to the child. Since the introduction of the HIV screening the number of children
      born with HIV has fallen dramatically.

PMID- 21176249
TI  - [Resuscitation of a pregnant patient--don't hesitate to perform a perimortem
      caesarean section].
AB  - Cardiac arrest is a rare and life-threatening complication during pregnancy. We
      present the case of a 26-year-old patient in her first pregnancy who during
      induction of labour at 41 weeks had a cardiac arrest caused by an amniotic fluid
      embolism. As part of the resuscitation procedure, a perimortem caesarean section
      was performed in the delivery room within five minutes. Following the caesarean
      section, she developed diffuse intravascular coagulation and massive, life
      threatening haemorrhage which necessitated supravaginal uterus amputation.
      Afterwards mother and son recovered well and were discharged from hospital in
      good condition after 13 days. Pregnancy-induced changes in anatomy and physiology
      warrant a different approach during resuscitation. All medical personnel involved
      in the care of pregnant women should be trained to act promptly in acute
      situations. Training should increase knowledge of the aforementioned changes and
      stress the importance of performing a perimortem caesarean section, when
      necessary, on site and without hesitation.

PMID- 21176250
TI  - [Statistical significance or clinical relevance?].
AB  - This article evaluates the concept of 'minimal clinically important difference'
      (MCID) through the results of two studies. The first study was a randomised trial
      in patients with Parkinson's disease claiming a positive effect of treatment with
      rasagiline over placebo, based on statistical differences in ordinal outcome
      measures. However, the clinical relevance of the findings according to the
      concept of MCID was not taken into consideration. In the second study, MCIDs were
      defined by several methods in a large trial in patients with chronic inflammatory
      demyelinating polyneuropathy receiving intravenous immunoglobulin (IGIV) or
      placebo. In that study, the differences in outcomes between the intervention
      group and the placebo group were not only statistically significant, but also
      clinically relevant, in favour of the intervention group. This was demonstrated
      using various MCID cut-off values.

PMID- 21176251
TI  - [Doubts about the efficacy of fall-prevention programmes for the elderly].
AB  - Multifactorial fall-prevention programmes are often not effective in preventing
      falls and functional decline. This is also the case in the recently published
      study of de Vries et al. Several causes for this lack of efficacy can be given.
      An important finding in the Dutch population is that a pragmatic
      multidisciplinary fall-prevention programme has no added benefit over and above
      normal care. This is probably because in the Dutch situation, the GP has already
      adapted many aspects of multifactorial fall analysis into the integrated care he
      or she provides to the elderly patient.

PMID- 21176252
TI  - [Platypnea-orthodeoxia syndrome].
AB  - An 82-year-old woman presented with dyspnoea and palpitations. The patient was
      admitted to the cardiology ward on suspicion of atrial fibrillation and reduced
      cardiac output. Examination revealed position-dependent deoxygenation. Once acute
      cardiac or pulmonary pathologies were excluded a diagnosis of platypnea
      orthodeoxia was considered. Diagnosis was confirmed by transoesophageal contrast
      echocardiography, which showed a patent foramen ovale. Curative treatment
      consisted of percutaneous closure of the foramen ovale. A persistent asymptomatic
      foramen ovale is common and can be revealed in later life. Platypnea-orthodeoxia
      syndrome is a relatively unfamiliar disorder.

PMID- 21176253
TI  - [A series about the value of physical examination].
AB  - This article is the introduction to a new series in the Nederlands Tijdschrift
      voor Geneeskunde about the value of physical examination. Associated with this
      series, on the website (www.ntvg.nl) there are chapters of the new textbook on
      physical examination and films about carrying out physical examinations. Although
      physical examination is an essential part of the diagnostic process, often little
      attention is paid to the correct execution of the examination and there is
      insufficient knowledge of the value of the findings. The diagnostic process
      usually involves analysing all the information from the patient's history and a
      physical examination. However, research has only been done on the value of
      specific tests and even that is very limited. The most important measure we use
      for the results of a physical examination is the likelihood ratio, which shows
      how the likelihood of presence or absence of a disease changes depending on the
      examination results.

PMID- 21176254
TI  - [A man with a painful hip after a soccer incident].
AB  - A 53-year-old man presented with a shortened exo-rotated left leg and a flexed
      painful left hip after a soccer accident. X-ray of the hip revealed an anterior
      hip dislocation, for which the patient was successfully treated by reduction of
      the hip replacement in the operating room.

PMID- 21176255
TI  - [Antonio Maria Valsalva (1666-1723) and his manoeuvre].
AB  - Valsalva studied and lived in Bologna, where he was a pupil of Malpighi and
      teacher of Morgagni. He wrote the first book detailing the structure and function
      of the ear. Valsalva advocated expiration against a closed mouth and nose as a
      method to evacuate purulent matter from the brain. His hypothesis of foramina
      between the intracranial cavity and the ear was eventually not confirmed. The
      phenomenon of weakening and slowing of the pulse by an increase in intrathoracic
      pressure was first described in the 19th century, but has also been named the
      'Valsalva manoeuvre'.

PMID- 21176256
TI  - [Shedding new light on vitamin D--reassessment of an essential prohormone].
AB  - Vitamin-D deficiency is no longer to be seen only as a cause of osteomalacia,
      rickets and osteoporosis. There is a causal relationship with muscle function and
      also with the functioning of our immune system. Furthermore, vitamin-D deficiency
      is associated with a higher risk of autoimmune diseases and several forms of
      malignancy, such as prostate, colon and breast cancer. Optimal serum
      concentration is under discussion which has already led to modification of the
      recommendations on vitamin-D supplementation. At present, European consensus on
      25-hydroxyvitamin-D serum concentrations seems to be a minimum of 50 nmol/l and a
      target of 75 nmol/l. The majority of the elderly and of non-Western immigrants
      are deficient or severely deficient in vitamin D and correction of such a
      deficiency with bolus therapy should be considered. Awareness of a vitamin-D
      deficiency is needed in unexplained complaints of muscle weakness or muscle pain,
      and in the risk groups, such as the elderly, non-Western immigrants, the
      chronically ill, indoor living and institutionalized, those who habitually use
      sun protection cream, and severely obese patients.

PMID- 21176257
TI  - [Secondary prevention following myocardial infarction may be improved. Long-term
      medication use according to practice guidelines].
AB  - OBJECTIVE: To determine the percentage of myocardial infarction patients in the
      Netherlands still using medication for secondary prevention according to current
      practice guidelines at the long term. DESIGN: Follow-up study of a prospective
      randomised clinical trial. METHOD: From 1071 myocardial infarction patients
      participating in a trial we obtained data on long-term medication use during
      follow-up. The medication was compared with the recommendations of the European
      Society of Cardiology for the use of statins, antithrombotics, renin-angiotensin
      aldosterone system inhibitors and beta-blockers. RESULTS: From 922 patients (86%)
      data were available on the medication use at on average 36 months (SD: 7) after
      myocardial infarction. At that time, 51% of the patients used medication
      conformable to the guideline. The use of ACE-inhibitors or angiotensin II
      receptor blockers was lowest (71% of all patients). At discharge from the
      hospital the patient group using medication according to the guideline during
      long-term follow-up had significantly more often received medication conformable
      to the guideline. CONCLUSION: Approximately half of the patients with myocardial
      infarction still adhere to use of medication for secondary prevention according
      to current guidelines at the long term. In particular, adherence of the
      cardiologist prescribing medication at discharge deserves more attention.

PMID- 21176258
TI  - [Treatment of constipation in the palliative care phase].
AB  - Constipation is a common problem with a considerable negative impact on quality
      of life in patients who receive palliative care. Over 35% of patients with heart
      failure, chronic obstructive pulmonary disease or cancer have constipation. In
      the palliative phase constipation often has multiple causes. Treatment of
      constipation consists of both medical treatment with laxatives and non-medical
      treatment. A specific recommendation for the use of laxatives cannot be made
      because of the lack of comparative trials. The choice of what laxative to use can
      only be made on the basis of clinical experience, mechanism of action, personal
      preference of the patient and costs. Prophylactic use of laxatives is indicated
      to prevent constipation when initiating constipation inducing medication such as
      opioids. In treatment-resistant constipation prucalopride, colchicine or
      misoprostol may be effective. Opioid-antagonists such as naloxone and
      methylnaltrexone are effective in patients with persistent opioid-induced
      constipation despite the use of laxatives.

PMID- 21176259
TI  - [Hysteroscopy to relieve IUD-related symptoms].
AB  - A levonorgestrel-releasing intrauterine device (LNG-IUD) had been placed in 4
      patients, aged 33, 27, 46 and 27 years. They subsequently experienced symptoms
      that were possibly related to the IUD, such as haemorrhagic discharge, pain and
      dyspareunia. Patients who have persistent symptoms after IUD placement need to be
      examined. If a malpositioned IUD is suspected, outpatient vaginoscopic
      hysteroscopy should be considered. Hysteroscopy can reveal the cause of the
      symptoms. Furthermore, an IUD that is incorrectly positioned can be repositioned
      during the same procedure. One advantage to this is that unnecessary removal of
      an IUD may be prevented. The first patient referred to in this article had lost
      confidence in the IUD and requested its removal. In the second patient, the IUD
      had perforated the anterior wall of the uterus and it was removed as well. In the
      third patient, the IUD had perforated the posterior wall of the uterus, but it
      was repositioned during the hysteroscopy. In the last patient, hysteroscopy
      showed the IUD to be in a transverse position, but this could be corrected
      immediately.

PMID- 21176261
TI  - [Patient-centred care requires attention to context].
AB  - Quality of care is often measured as the level to which guidelines are followed.
      The level to which care providers take into account the context of the patient,
      such as patient transportation needs, caretaker responsibilities or patient
      inability to take medication frequently because of a stressful job, is seldom
      used as a measure of quality of care. Recent evidence has shown that care
      providers pay limited attention to patient context when suggesting a plan of
      care. We discuss ways for care providers to take more account of the context of
      the patient, which will increase the quality of care. We suggest the development
      of context-related indicators to measure quality of care.

PMID- 21176260
TI  - [Adult-onset Still's disease and haemophagocytic syndrome].
AB  - A 49-year-old woman with a history of adult-onset Still's disease (AOSD)
      presented with fever, general malaise and a rash. Laboratory blood testing
      revealed an extremely high level of serum ferritin, essentially restricting the
      differential diagnosis to either haemophagocytic syndrome as a complication of
      AOSD, or a flare-up of the latter. Haemophagocytosis as a complication of AOSD
      was diagnosed in our patient. After treatment with prednisone, she fully
      recovered and the serum ferritin returned to a normal level. Haemophagocytic
      syndrome is a rare but potentially life-threatening complication of
      lymphoproliferative and autoimmune diseases, as well as of viral infections. It
      is characterised by high fever, hepatosplenomegaly, cytopenia and extremely high
      levels of serum ferritin. Activation of macrophages and histiocytes induces
      phagocytosis of erythrocytes in the bone marrow and other parts of the
      reticuloendothelial system. The fact that haemophagocytic syndrome and AOSD are
      often described together, and coincide with extremely elevated serum ferritin
      levels characteristic to both entities, suggests a related pathogenesis.

PMID- 21176262
TI  - [A girl with a lacunar skull].
AB  - Following trauma, an X-ray was made of the head of a 5-year-old mentally impaired
      girl. A lacunar skull ('Luckenschadel') was seen, which was a coincidental
      finding. A lacunar skull develops when the fetal skull is poorly ossificated,
      probably due to a lack of distention of the cerebral ventricles.

PMID- 21176264
TI  - [Vascular cognitive impairment].
AB  - Vascular cognitive impairment is more prevalent than vascular dementia, but at
      present this condition is not recognized adequately. Vascular cognitive
      impairment does not manifest itself as dementia after stroke, but as gradually
      commencing cognitive impairment with or without a gait disorder. The clinical
      picture is caused by white matter damage and multiple lacunar strokes, sometimes
      called 'silent' strokes. Patients with vascular cognitive impairment have an
      increased risk of cardiovascular events, falling, and further cognitive decline,
      eventually evolving into dementia. It is important to recognize these patients
      and to provide advice and appliances and equipment, treat cardiovascular risk
      factors and prevent the complications of falling.

PMID- 21176263
TI  - [Passive smoking in young children in the Netherlands sharply decreased since
      1996].
AB  - OBJECTIVE: To describe the prevalence of passive smoking in young children and to
      analyse the trends in the prevalence of passive smoking in young children over
      time. DESIGN: Retrospective, descriptive. METHOD: Data were derived from yearly
      samples of 500 to 800 adults living with children aged 0-4 years, who had
      completed a questionnaire on passive smoking and on several background
      characteristics. Data from 1996-2009 were analysed for trends in the prevalence
      of passive smoking and the relationship with characteristics such as smoking
      habits and socioeconomic status (SES). RESULTS: The percentage of families with
      young children (0-4 years) reporting smoking at home decreased sharply, from 64
      in 1996 to 19 in 2009. Passive smoking sharply decreased as well. The prevalence
      of smoking at home in the presence of children was 10% in 2009 versus 48% in
      1996. After the implementation of the smoking ban in hotels, restaurants and pubs
      in 2008 a sharper decrease in passive smoking at home was found than in the
      preceding years, except for the families with a lower SES. Passive smoking still
      occurs in 14% of families with children aged 2-4, in 29% of the families with a
      lower SES and in 22% of the families with smokers. Nearly 40% of the heavy
      smokers still expose their child to tobacco smoke at home. CONCLUSION: There is a
      distinct decrease in passive smoking at home in young children. In spite of this,
      there still are some groups of children that are regularly exposed to tobacco
      smoke. Preventive programs should be optimized to continue the decrease in
      passive smoking in these groups.

PMID- 21176265
TI  - [Paraneoplastic pemphigus in a patient with non-Hodgkin lymphoma].
AB  - A 53-year-old man with non-Hodgkin lymphoma developed red, flaky skin, which was
      initially suggestive of a drug reaction. He also had pneumonia, for which he was
      admitted for antibiotic treatment. During admission the skin picture changed and
      blisters and erosions appeared on his body. Skin biopsy and immunological
      examination led to the diagnosis of paraneoplastic pemphigus (PNP). The patient
      died five months after the diagnosis of PNP due to PNP pneumonia. PNP is a rare
      and often aggressive bullous disease with an autoimmune pathogenesis, associated
      with underlying lymphoproliferative disease. It is characterised by a
      polymorphous skin rash, painful mucosal erosions, sometimes with respiratory
      complications due to bronchiolitis obliterans. Diagnosis is based on clinical,
      histological and immunological findings. The prognosis is unfavourable; death
      occurs in 90 percent of patients. This case illustrates the importance of
      histology, immunofluorescence microscopy, and immunoserology in misunderstood
      skin disorders in patients with lymphoproliferative disease.

PMID- 21176266
TI  - [Unnatural death due to child abuse--forensic autopsies 1996-2009].
AB  - OBJECTIVE: To evaluate the number of cases of fatal child abuse in minors on whom
      forensic autopsy was carried out in the Netherlands during the period 1996-2009
      and to compare the 1996 data with Dutch data published earlier by Kuyvenhoven et
      al. (a questionnaire study among general practitioners and paediatricians).
      DESIGN: Descriptive retrospective study. METHOD: Cases of unnatural death from
      all forensic autopsies on fetuses, children and young adults (> 24 weeks and < 18
      years; n = 688) over the past 14 years (1996-2009) were retrospectively analyzed
      for child abuse. By means of death certificates and suspected cause of death, the
      actual outcomes of the 1996 data were compared with those of the study of
      Kuyvenhoven et al. RESULTS: Over the past 14 years, in 445 of 688 forensic cases
      (65%) in this study population, cause of death was demonstrated to be unnatural.
      Of these deaths, 54% (n = 239/445) were unnatural and non-accidental due to child
      abuse. This corresponded with an annual average of 15 (30%) 'proven' and 2 (5%)
      'highly probable' cases of fatal child abuse. The total number of abandoned
      babies, foundlings and otherwise, was on average 4 per year. In 1996 57% (13/23)
      of fatal child abuse cases were not represented in the data published by
      Kuyvenhoven et al. CONCLUSION: Of the 49 foetuses, children and young adults on
      whom forensic autopsy was carried out in the Netherlands each year, 17 (35%) died
      due to proven or highly probable child abuse. In 1996 more than half of the
      number of fatal cases of child abuse of the Netherlands Forensic Institute were
      not represented in the study of Kuyvenhoven et al. In both this study and in the
      one of Kuyvenhoven underreporting is highly probable.

PMID- 21176267
TI  - [An infant with unexplained epilepsy].
AB  - A 6-month-old male infant with an unremarkable past medical history was admitted
      to the emergency department in an epileptic state. The seizures were resistant to
      treatment with conventional drugs. The child was sedated, intubated and admitted
      to the intensive care department. Despite extensive investigations no underlying
      disease was found. The seizures persisted and the child was repeatedly admitted
      to the hospital. Four months after the first presentation, ventricular
      fibrillation occurred from which the child was successfully resuscitated. His
      stomach appeared to contain a disinfectant and a severe ethanol-intoxication was
      found, leading to the diagnosis "Munchausen syndrome by proxy". The incidence of
      this syndrome is underestimated. Recognition of this potentially fatal phenomenon
      is often difficult, resulting in a delay in diagnosis. Paediatricians and general
      practitioners should be aware of this syndrome in children presenting with an
      unusual disease or an unusual medical history reported by the parents or care
      providers.

PMID- 21176268
TI  - [Physical diagnostic examination of dehydration].
AB  - Dehydration is an important cause of morbidity and mortality for children and the
      elderly. Acute loss of weight is the most reliable measure of dehydration. In
      addition, a range of physical diagnostic findings are used for measuring
      dehydration; separate clinical findings have very little predictive value. In
      clinical practice the need for further investigation and rehydration treatment
      can be assessed by combining history and physical examination.

PMID- 21176269
TI  - [MRI diagnostics should be available to general practice].
AB  - With its high negative predictive value, MRI is of great value to the general
      practitioner's (GP) unequivocal task of excluding pathology in a large proportion
      of their patient population. While GPs prefer open access to MRI, insurance
      companies prefer to limit or discourage GP use of MRI, the main fear being
      unlimited unnecessary requests. Studies have shown these fears to be unfounded.
      Dutch Health Care Insurance Board (CVZ) regulations stipulate that GPs should
      have access to MRI on specific indications that are described in the Dutch
      College of General Practitioners' (NHG) practice guidelines. In the Netherlands,
      Alkmaar Medical Center (MCA) has offered open access to MRI since 1993 (knee) and
      2006 (hernia nuclei pulposi), with excellent results. The percentage of normal
      report rates and of pathological findings of GPs is comparable to that of both
      neurologists and orthopaedic surgeons. Open access to MRI helps to speed up the
      diagnostic process, reduce outpatient waiting lists and limit unnecessary
      consultations. International publications have reported the cost-effectiveness of
      MRI. Experience both outside the Netherlands and at MCA has shown that open
      access to MRI results in reduced waiting lists and enhanced cost-effectiveness.
      This is best practice and should be incorporated into NHG practice guidelines.

PMID- 21176271
TI  - Phyllanthus niruri as a promising alternative treatment for nephrolithiasis.
AB  - In spite of considerable efforts to identify effective treatments for
      urolithiasis, this is a goal yet to be achieved. This review summarizes
      experimental and clinical data evaluating the effect of the plant Phyllanthus
      niruri, a plant with worldwide distribution, as a potential agent to prevent
      and/or to treat urolithiasis The review is based on data from the literature and
      on the results obtained by our group from either in vivo/in vitro experiments or
      clinical studies. Phyllanthus niruri has been shown to interfere with many stages
      of stone formation, reducing crystals aggregation, modifying their structure and
      composition as well as altering the interaction of the crystals with tubular
      cells leading to reduced subsequent endocytosis. The clinical beneficial effects
      of Phyllanthus niruri may be related to ureteral relaxation, helping to eliminate
      calculi or to clear fragments following lithotripsy, or also to a putative
      reduction of the excretion of urinary crystallization promoters such as calcium.
      No adverse renal, cardiovascular, neurological or toxic effects have been
      detected in either of these studies. Altogether, these studies suggest a
      preventive effect of Phyllanthus niruri in stone formation or elimination, but
      still longer-term randomized clinical trials are necessary to confirm its
      therapeutic properties.

PMID- 21176272
TI  - The novel prostate cancer antigen 3 (PCA3) biomarker.
AB  - PCA3 is a prostate specific, nonprotein coding RNA that is significantly over
      expressed in prostate cancer, without any correlation to prostatic volume and/or
      other prostatic diseases (e.g. prostatitis). It can now easily be measured in
      urine with a novel transcription-mediated amplification based test.
      Quantification of PCA3 mRNA levels can predict the outcome of prostatic biopsies
      with a higher specificity rate in comparison to PSA. Several studies have
      demonstrated that PCA3 can be used as a prognostic marker of prostate cancer,
      especially in conjunction with other predictive markers. Novel PCA3-based
      nomograms have already been introduced into clinical practice. PCA3 test may be
      of valuable help in several PSA quandary situations such as negative prostatic
      biopsies, concomitant prostatic diseases, and active surveillance. Results from
      relevant clinical studies, comparative with PSA, are warranted in order to
      confirm the perspective of PCA3 to substitute PSA.

PMID- 21176273
TI  - The beginning of the 21st century: a paradigm shift in the surgical management of
      renal cell carcinoma in South America.
AB  - PURPOSE: The incidence of renal cell carcinoma (RCC) has been rising by 2.3 to
      4.3% every year over the past three decades. Previously, RCC has been known as
      the internist's tumor; however, it is now being called the radiologist's tumor
      because 2/3 are now detected incidentally on abdominal imaging. We compared
      patients who were treated toward the end of the 20th century to those treated
      during the beginning of the 21st century with regard to RCC size and type of
      surgical treatment. MATERIALS AND METHODS: The study included 226 patients. For
      analysis of tumor size, we considered a cut point of <4 cm and>4 cm. For analysis
      of type of surgery performed, we considered radical and partial nephrectomy.
      RESULTS: After the turn of the century, there was a reduction of 1.57+/-0.48 cm
      in the size of the RCC that was operated on. Nephron sparing surgeries were
      performed in 17% of the cases until the year 2000, and 39% of the tumors were <4
      cm. From 2001, 64% of the tumors measured<4 cm and 42% of the surgeries were
      performed using nephron sparing techniques. Mean tumor size was 5.95 cm (+/-3.58)
      for the cases diagnosed before year 2000, and cases treated after the beginning
      of 21st century had a mean tumor size of 4.38 cm (+/-3.27). CONCLUSIONS: Compared
      with the end of the 20th century, at the beginning of the 21st century due to a
      reduction in tumor size it was possible to increase the number of nephron sparing
      surgeries.

PMID- 21176274
TI  - Transperitoneal laparoscopic pyeloplasty: Brazilian initial experience with 55
      cases.
AB  - PURPOSE: To evaluate prospectively the results obtained in 55 patients undergoing
      laparoscopic pyeloplasty through transperitoneal access. MATERIALS AND METHODS:
      From January 2005 to July 2009, fifty-five patients between 13 and 64 years old,
      were treated for ureteropelvic junction (UPJ) stenosis via a transperitoneal
      laparoscopy. All patients had clinical symptoms of high urinary obstruction and
      hydronephrosis confirmed by imaging methods. Anderson-Hynes dismembered
      pyeloplasty was performed in 51 patients and Fenger technique in the other 4
      cases. Patients were clinically and imaging evaluated in the postoperative period
      at 3 and 6 months and then followed-up annually. RESULTS: The operative time
      ranged from 95 to 270 min. The mean hospital stay was 2 days. The average blood
      loss was 170 mL. The time to return to normal activities ranged from 10 to 28
      days. Anomalous vessels were identified in 27 patients, intrinsic stenosis in 23
      patients and 5 patients had high implantation of the ureter. Laparoscopic
      pyelolithotomy was successfully performed in 6 patients with associated renal
      stones. That series monitoring ranged from 1 to 55 months. One patient had longer
      urinary fistula (11 days), 3 patients had portal infection and 6 patients had
      prolonged ileus. There was one conversion due to technical difficulties. From the
      later postoperative complications, 2 patients had re-stenosis, one determined by
      Anderson-Hynes technique and the other by Fenger technique. The success rate was
      95.65%. CONCLUSIONS: Laparoscopic pyeloplasty has functional results comparable
      to conventional open technique. It offers less morbidity, with aesthetic and post
      operative convalescence benefits and lower complication rates.

PMID- 21176275
TI  - Do all patients with newly diagnosed prostate cancer need staging radionuclide
      bone scan? A retrospective study.
AB  - PURPOSE: Define a group of patients with newly diagnosed prostate cancer, whose
      risk of bone metastasis is low enough to omit a bone scan staging study.
      MATERIALS AND METHODS: From 2003 to 2009, the medical records of patients who
      were newly diagnosed with prostate cancer were retrospectively reviewed. The data
      collected included: age, digital rectal examination, serum prostate specific
      antigen (PSA), Gleason score, clinical T stage, and bone isotope scan. Patients
      were divided into two groups according to the results of bone isotope scan;
      positive group and negative group. A univariate and multivariate binary logistic
      regression was used to analyze the results. RESULTS: Of the 106 patients, 98 had
      a complete data collection and were entered into the study. The median age of the
      patients was 70.5 years and patients with a positive bone scan was 74 years,
      significantly higher than for patients with negative scans (69 years) (p=0.02).
      Bone metastasis was detected in 39 cases (39.7%). In all patients with clinical
      T1-2 stage, a Gleason score of <8 and PSA<=20 ng/mL, the bone isotope scans were
      negative. In univariate analysis, PSA (>20 ng/mL) and Gleason score (>7) were
      independently predictive of positive bone scan, while clinical stage was not.
      CONCLUSION: Staging bone scans can be omitted in patients with a PSA level of
      <=20 ng/mL, and Gleason score<8. Our results suggest that by considering the
      Gleason score and PSA, a larger proportion of patients with prostate cancer could
      avoid a staging bone scan.

PMID- 21176276
TI  - Racial differences in hypogonadal improvement and prostate-specific antigen
      levels in hypogonadal men treated with testosterone replacement therapy.
AB  - PURPOSE: To observe hypogonadal men undergoing testosterone replacement therapy
      (TRT) and assess racial differences in hypogonadal improvement and prostate
      specific antigen (PSA) levels. MATERIALS AND METHODS: In a retrospective
      analysis, 75 hypogonadal men were followed for an average 34 months after
      initiating TRT. Total testosterone and PSA levels were assessed every 6 months,
      and patients diagnosed with prostatitis or prostate cancer during treatment were
      excluded. RESULTS: For 16 African American men, the average age at diagnosis of
      hypogonadism was 53.5 years, compared with 57.8 years in 59 Caucasian men (p=NS).
      Pre- and post-treatment testosterone was 219 ng/dL and 310 ng/dL in African
      American men, and 247 ng/dL and 497 ng/dL in Caucasian men (p=NS). Symptomatic
      response was 81% in African American men and 93% in Caucasian men (p=NS).
      Baseline PSA level was 1.32 ng/mL in African American men and 1.27 ng/mL in
      Caucasian men, and there was no significant difference in PSA between racial
      groups at 6-month intervals, although there was a small decreasing trend in the
      PSA of African Americans compared with Caucasians. CONCLUSIONS: Hypogonadal
      African American men have a similar normalization of testosterone and symptomatic
      response as hypogonadal Caucasian men, and PSA levels remain stable over time in
      both groups. In this hypogonadal cohort, in contrast to studies of eugonadal men,
      higher PSA levels in African Americans were not observed.

PMID- 21176277
TI  - The approach to the difficult urethral catheterization among urology residents in
      the United States.
AB  - PURPOSE: To determine the prevalence of different approaches to the difficult
      urethral catheterization (DUC) among urology residents (UR) in the United States
      (US). MATERIALS AND METHODS: An email invitation to participate in an online
      survey regarding DUC was sent to 267 UR and to 22 urology program coordinators
      for them to forward to their residents. 142 UR completed the survey. RESULTS:
      After the initial unsuccessful attempt by a nurse, 92% of UR attempted a catheter
      prior to resorting to other modalities. The most common choice of the first
      catheter was a Coude (76%) size 18F (51%). For situations where multiple sizes
      and types of catheters (12-20F) were used without success, 3 scenarios were
      proposed: 1) Catheter passed the bulbomembranous urethra (BMU) and patient had
      previous history of transurethral resection of the prostate or radical retropubic
      prostatectomy, 2) Catheter passed the BMU and no urologic history, 3) Catheter
      did not pass the BMU and no urologic history. Flexible cystoscopy was used in
      74%, 62% and 63%; blind passage of a glidewire was second with 15%, 23% and 20%;
      and blind use of filiforms and followers was chosen in 7%, 9% and 9% of the
      scenarios respectively. CONCLUSIONS: The most common approach to the DUC among UR
      in the US involves using an 18F Coude catheter first. After trying one or more
      urethral catheters, UR most commonly resort to flexible cystoscopy as opposed to
      the blind placement of glide wires or filiforms/followers.

PMID- 21176278
TI  - Laparoendoscopic Pfannenstiel nephrectomy using conventional laparoscopic
      instruments--preliminary experience.
AB  - PURPOSE: To confirm the feasibility of the laparoendoscopic Pfannenstiel
      nephrectomy using conventional laparoscopic instruments. MATERIALS AND METHODS:
      Since March 2009, laparoscopic nephrectomy through a Pfannenstiel incision has
      been performed in selected patients in our service. The Veress needle was placed
      through the umbilicus which allowed carbon dioxide inflow. One 5 mm (or 10 mm)
      trocar was placed at the umbilicus for the laparoscope, to guide the placement of
      three trocars over the Pfannenstiel incision. Additional trocars were placed as
      follows: a 10 mm in the midline, a 10 mm ipsilateral to the kidney to be removed
      (2 cm away from the middle one), and a 5 mm contralateral to the kidney to be
      removed (2 cm away from the middle one). The entire procedure was performed using
      conventional laparoscopic instruments. At the end of the surgery, trocars were
      removed and all three incisions were united into a single Pfannenstiel incision
      for specimen retrieval. RESULTS: Five nephrectomies were performed following this
      technique: one atrophic kidney, one kidney donation, two renal cancers and one
      bilateral renal atrophy. Median operative time was 100 minutes and median
      intraoperative blood loss was 100 cc. No intraoperative complications occurred
      and no patients required blood transfusion. Median length of hospital stay was 1
      day (range 1 to 2 days). CONCLUSIONS: The use of the Pfannenstiel incision for
      laparoscopic nephrectomy seems to be feasible even when using conventional
      laparoscopic instruments, and can be considered a potential alternative for
      traditional laparoscopic nephrectomy.

PMID- 21176279
TI  - Extracorporeal shock wave lithotripsy in the treatment of pediatric urolithiasis:
      a single institution experience.
AB  - PURPOSE: To compare the efficacy and safety of the electromagnetic lithotripter
      in the treatment of pediatric lithiasis to that of the earlier electrohydraulic
      model. MATERIALS AND METHODS: Two groups of children with lithiasis aged between
      10 and 180 months who underwent extracorporeal shock wave lithotripsy (ESWL). In
      the first group (26 children), ESWL was performed by using the electrohydraulic
      MPL 9000X Dornier lithotripter between 1994 and 2003 while in the second group
      (19 children) the electromagnetic EMSE 220 F--XP Dornier lithotripter was used
      from April 2003 to May 2006. RESULTS: In the first group, 21/26 children (80.7%)
      were stone free at first ESWL session. Colic pain resolved by administration of
      an oral analgesic in 6 (23%), brief hematuria (<24 h) resolved with increased
      fluid intake in 5 (19.2%), while slightly elevated body temperature (<38 degrees
      C) occurred in 4 (15.3%). Four children (15.3%) failed to respond to treatment
      and were treated with ureteroscopy. In the second group 18/19 children were
      completely stone free at first ESWL session (94.7%). Complications were
      infrequent and of minor importance: colic pain treated with oral analgesic
      occurred in 1 (5.26%), brief hematuria (<24 h), resolved with increased fluid
      intake in 4 (21%) and slightly elevated body temperature (<38 degrees  C)
      monitored for 48 hours occurred in 6 (31.5%). Statistical analysis showed that
      electromagnetic lithotripter is more efficacious and safer than the earlier
      electrohydraulic model. CONCLUSIONS: Technological development not only has
      increased efficacy and safety of lithotripter devices in treating pediatric
      lithiasis, but it also provided less painful lithotripsy by eliminating the need
      for general anesthesia.

PMID- 21176280
TI  - Botulinum toxin A in the treatment of spinal cord injury patients with refractory
      neurogenic detrusor overactivity.
AB  - PURPOSE: To evaluate the efficacy of botulinum toxin type A injections in the
      detrusor muscle in patients with spinal cord injury and urinary incontinence due
      to detrusor overactivity and refractory to anticholinergic agents. MATERIALS AND
      METHODS: We prospectively evaluated 22 patients with spinal cord injuries, whose
      bladders were emptied by intermittent catheterization. All patients had detrusor
      overactivity and urinary incontinence that proved difficult to treat, despite
      using high doses of two different anticholinergics. The pre-treatment assessment
      included a complete urodynamic study and ultrasonography of the kidneys and
      urinary tract. A one-month follow-up was completed with urodynamic evaluation and
      the clinical response was evaluated through outpatient consultations and
      telephone contact. RESULTS: After the procedure, the maximum cystometric capacity
      and the bladder reflex volume increased, whereas the maximum detrusor pressure
      and compliance decreased. The mean duration of continence was 7+/-7 months. In 18
      patients (81.8%), it was necessary to administer anticholinergics to achieve
      continence. Five patients (22.7%) had indication of reinjection, and augmentation
      cystoplasty was indicated in 9 patients (40.9%). CONCLUSION: The use of botulinum
      toxin in the treatment of neurogenic detrusor overactivity refractory to
      anticholinergics is an option before more invasive treatments, such as
      augmentation cystoplasty, are attempted. In our study as well as in the
      literature, there was improvement in most urodynamic parameters. Overall, 40.9%
      of patients underwent augmentation cystoplasty and 81.8% of patients needed
      anticholinergic agents to reach urinary continence. Further studies are necessary
      to improve the procedure and to achieve better clinical results.

PMID- 21176281
TI  - Development of a computer assisted gantry system for gaining rapid and accurate
      calyceal access during percutaneous nephrolithotomy.
AB  - PURPOSE: To design a simple, cost-effective system for gaining rapid and accurate
      calyceal access during percutaneous nephrolithotomy (PCNL). MATERIALS AND
      METHODS: The design consists of a low-cost, light-weight, portable mechanical
      gantry with a needle guiding device. Using C-arm fluoroscopy, two images of the
      contrast-filled renal collecting system are obtained: at 0-degrees (perpendicular
      to the kidney) and 20-degrees. These images are relayed to a laptop computer
      containing the software and graphic user interface for selecting the targeted
      calyx. The software provides numerical settings for the 3 axes of the gantry,
      which are used to position the needle guiding device. The needle is advanced
      through the guide to the depth calculated by the software, thus puncturing the
      targeted calyx. Testing of the system was performed on 2 target types: 1)
      radiolucent plastic tubes the approximate size of a renal calyx (5 or 10 mm in
      diameter, 30 mm in length); and 2) foam-occluded, contrast-filled porcine
      kidneys. RESULTS: Tests using target type 1 with 10 mm diameter (n=14) and 5 mm
      diameter (n=7) tubes resulted in a 100% targeting success rate, with a mean
      procedure duration of 10 minutes. Tests using target type 2 (n=2) were both
      successful, with accurate puncturing of the selected renal calyx, and a mean
      procedure duration of 15 minutes. CONCLUSIONS: The mechanical gantry system
      described in this paper is low-cost, portable, light-weight, and simple to set up
      and operate. C-arm fluoroscopy is limited to two images, thus reducing radiation
      exposure significantly. Testing of the system showed an extremely high degree of
      accuracy in gaining precise access to a targeted renal calyx.

PMID- 21176282
TI  - Effect of hydrogen peroxide on rabbit urinary bladder citrate synthase activity
      in the presence and absence of a grape suspension.
AB  - PURPOSE: The etiology of obstructive bladder dysfunction includes free radical
      damage to mitochondria. Feeding rabbits a standardized grape suspension protects
      the ability of the bladder to contract and empty in part by preventing
      mitochondrial damage, thus maintaining smooth muscle and mucosal metabolism. The
      objective of the current study is to determine the direct effect of this grape
      suspension on the response of mitochondria to the oxidative effects of hydrogen
      peroxide. MATERIALS AND METHODS: Six male rabbits were anesthetized with sodium
      pentobarbital and the bladders excised. Four full thickness strips were obtained
      for contractile studies and the balance separated into smooth muscle and mucosa
      compartments by blunt dissection. The effect of hydrogen peroxide on the
      contractile response to field stimulation was quantitated. Each tissue was
      homogenized and the effects of increasing concentrations of hydrogen peroxide in
      the presence and absence of grape suspension on citrate synthase activity was
      determined. RESULTS: Citrate synthase activity was significantly higher in the
      mucosa than in the muscle. The grape suspension had no effect on control citrate
      synthase activity. However, the grape suspension provided significant protection
      of both smooth muscle and mucosal citrate synthase activity. CONCLUSIONS: These
      studies support the conclusion that the grape suspension provides direct
      protection of mitochondrial function.

PMID- 21176283
TI  - Hematuria in a patient with persistent left cardinal vein crossing retroaortic to
      the right cardinal vein (inferior vena cava).

PMID- 21176300
TI  - Vulvar lichen sclerosus.

PMID- 21176301
TI  - The prevalence of gestational diabetes mellitus and glucose abnormalities in
      pregnant women with hepatitis C virus infection in British Columbia.
AB  - OBJECTIVE: There is evidence to support an association between diabetes mellitus
      (DM) and hepatitis C virus (HCV) infection. The insulin resistant state of
      pregnancy suggests a predisposition to developing gestational diabetes mellitus
      (GDM) in women infected with HCV. The aim of this study was to compare the
      prevalence of GDM and impaired glucose tolerance (IGT) of pregnancy between women
      infected with HCV and the general population of British Columbia screened for
      GDM. METHODS: The HCV cohort was drawn from a population-based prospective cohort
      of 148 pregnant women infected with HCV in British Columbia. GDM screening tests
      were completed in 84 women. The prevalence of GDM and IGT of pregnancy in the
      general population of British Columbia was estimated by acquiring 24 321 GDM
      screening tests performed by the two major laboratories in the province. RESULTS:
      Non-compliance was the primary reason for incomplete screening. The prevalence of
      GDM was 9.5% in the HCV cohort and 6.8% in the screened general population (chi
      square test P = 0.33). Similarly, there was no difference in IGT of pregnancy
      between the two cohorts (2.4% vs. 3.5%; chi-square test P = 0.57). CONCLUSION: A
      difference in the prevalence of either GDM or IGT of pregnancy was not detected
      between HCV-infected patients who were screened for GDM and those screened in the
      general population. Further studies are required to assess whether HCV infection
      is an independent risk factor for GDM.

PMID- 21176302
TI  - Does education level influence the decision to undergo elective repeat caesarean
      section among women with a previous caesarean section?
AB  - OBJECTIVE: Patient education level has been shown to affect health care outcomes
      in a variety of clinical contexts. The aim of this study was to evaluate whether
      maternal education level influences women to plan elective repeat Caesarean
      section rather than attempt a vaginal birth after Caesarean. METHODS: We
      conducted a retrospective cohort study of women with a previous Caesarean section
      who delivered at the Royal Victoria Hospital between 2001 and 2006. Education
      level was stratified as follows: </= 11 years (up to and including a high school
      diploma), 12 to 15 years (some college or university education), and >/= 16 years
      (university degree). We used unconditional logistic regression to calculate age
      adjusted estimates of the risk of having a planned Caesarean section. RESULTS:
      Among 18 673 deliveries in our cohort, 1915 were in women with a previous
      Caesarean section. Of these, 12.6% had a high school degree or less, 38.3% had
      some college or university education, and 49.1% had a university degree. Compared
      with women whose maximum education was a high school diploma, there was a higher
      rate of planned Caesarean section in women with some college or university
      education (OR 1.38; 95% CI 1.00 to 1.89, P = 0.047) and in women with a
      university degree (OR 1.42; 95% CI 1.04 to 1.94, P = 0.03). CONCLUSION: Higher
      education appears to be associated with an increased rate of elective repeat
      Caesarean section. Whether this is due to patient differences or physician bias,
      physicians should be aware of this disparity and should attempt to provide
      unbiased informed consent for all women regardless of their level of education.

PMID- 21176303
TI  - Maternal thyroid hormones in early pregnancy and risk of breech presentation.
AB  - OBJECTIVE: To evaluate the relationship between breech presentation at term (>/=
      37 weeks of gestation) and maternal thyroid hormone activity in early gestation.
      METHODS: We conducted a case-control study of thyroid hormone activity in 179
      women who delivered a live term infant in breech presentation (cases) and 849
      women who delivered a live term infant in cephalic presentation (control
      subjects). We used serum samples from prenatal screening at 15 to 16 weeks of
      gestation in 2006 and 2007 in Edmonton, Alberta. Maternal free thyroxin (fT4) and
      thyroid-stimulating hormone (TSH) were assayed. Logistic regression was used to
      estimate the odds of breech presentation in relation to the levels of thyroid
      hormones while controlling for potential confounders. RESULTS: There were no
      significant differences between the breech and cephalic groups when comparing fT4
      levels (OR 0.94 per pmol/L; 95% CI 0.88 to 1.00) or TSH levels (OR 1.16 per mU/L;
      95% CI 0.97 to 1.38) levels, after adjustment for all potential confounders.
      Segregating fT4 and TSH into quintiles showed the same pattern. Neither
      hypothyroidism nor hyperthyroidism was associated with risk of breech
      presentation. CONCLUSION: Our results provide evidence that maternal thyroid
      hormone levels at 15 to 16 weeks of gestation are not related to risk of breech
      presentation at birth in term infants.

PMID- 21176304
TI  - Repeat screening for sexually transmitted infection in adolescent obstetric
      patients.
AB  - OBJECTIVE: To determine if repeat screening for sexually transmitted infection is
      appropriate for adolescent obstetric patients and to identify any risk factors
      associated with increased risk of contracting a sexually transmitted infection
      (STI) during pregnancy. METHODS: We conducted a retrospective review of the
      medical records of adolescent obstetric patients seen over a five-year period in
      the Young Prenatal Program at the Hospital for Sick Children (Toronto, Ontario).
      RESULTS: Between January 2003 and December 2007, 201 patients with 211
      pregnancies attended the Young Prenatal Program. Of the 211 pregnancies reviewed,
      all patients had screening at baseline for HIV, syphilis, hepatitis B, chlamydia,
      gonorrhea, and trichomonas; 173 patients were screened in the third trimester,
      two were tested at another point in the pregnancy because of symptoms, and 161
      were screened at their postpartum visit. In 53 pregnancies, STI was diagnosed
      either during pregnancy or postpartum. Fourteen patients had multiple sexually
      transmitted infections for a total of 71 infections. Thirty-four infections were
      diagnosed at baseline, 15 in the third trimester, two because of symptoms, and
      seven were diagnosed postpartum. In patients who did not develop an STI during
      pregnancy, the previous use of contraception (excluding condoms), being in a
      relationship with the baby's father, and living with their partner were
      identified as significant protective factors against STI. There was a trend
      towards significance for contracting an STI in patients with a history of abuse,
      in those with a higher than average number of sexual partners, and in those with
      a younger than average age of coitarche. CONCLUSION: Sexually transmitted
      infections were diagnosed in 25.1% of adolescent pregnancies (53/211) in our
      cohort. Of the 71 sexually transmitted infections diagnosed, 22.5% (16/71) were
      diagnosed on routine third trimester screening. Because of the high rates of STI
      and the small number of identified risk factors, routine repeat screening in the
      third trimester for chlamydia, gonorrhea, and trichomonas is warranted in
      pregnant adolescents.

PMID- 21176305
TI  - Influences on decision making among primiparous women choosing elective caesarean
      section in the absence of medical indications: findings from a qualitative
      investigation.
AB  - OBJECTIVE: Patient-initiated elective Caesarean section (PIECS) is increasingly
      prevalent and is emerging as an urgent issue for individual maternity
      practitioners, hospitals, and policy makers, as well as for maternity patients.
      This qualitative study sought to explore women's experiences of the decision
      making process leading to elective operative delivery without medical indication.
      METHODS: We conducted 17 exploratory qualitative in-depth interviews with
      primiparous women who had undergone a patient-initiated elective Caesarean
      section in the absence of any medical indication. The study took place in five
      hospitals (three urban, two semi-rural) in British Columbia. RESULTS: The
      findings revealed three themes within the process of women deciding to have a
      Caesarean section: the reasons for their decision, the qualities of the decision
      making process, and the social context in which the decision was made. The
      factors that influenced a patient-initiated request for delivery by Caesarean
      section in participants in this study were diverse, culturally dependent, and
      reflective of varying degrees of emotional and evidence-based influences.
      CONCLUSION: PIECS is a rare but socially significant phenomenon. The a priori
      decision making of some women choosing PIECS does not follow the usual diagnosis
      intervention trajectory, and the care provider may have to work in reverse to
      ensure that the patient fully understands the risks and benefits of her decision
      subsequent to the decision having been made, while still ensuring patient
      autonomy. Results from this study provide a context for a woman's request for an
      elective Caesarean section without medical indication, which may contribute to a
      more efficacious informed consent process.

PMID- 21176306
TI  - Nausea and vomiting in pregnancy is not always nausea and vomiting of pregnancy.
AB  - The majority of pregnant women experience nausea and vomiting during pregnancy.
      However, nausea and vomiting in pregnancy is not always nausea and vomiting of
      pregnancy (NVP). The differential diagnosis of nausea and vomiting in pregnancy
      can be extensive and the underlying cause can sometimes be difficult to diagnose.
      However, the timing or onset of the symptoms is important in differentiating NVP
      from other causes. A thorough history and physical examination, with appropriate
      investigations, should be carried out in symptomatic women.

PMID- 21176307
TI  - Randomized comparison of goserelin versus suction curettage prior to Thermachoice
      II balloon endometrial ablation: one-year results.
AB  - OBJECTIVES: To evaluate the clinical outcomes following the use of goserelin and
      suction curettage prior to ThermaChoice II balloon endometrial ablation to treat
      menorrhagia. METHODS: Qualified patients (n = 105) were randomized to receive
      either goserelin 3.6 mg one month before or suction curettage immediately before
      undergoing thermal balloon endometrial ablation. All patients had negative
      Papanicolaou smears, normal endometrial histology, and normal findings on
      transvaginal sonography. Uterine bleeding was documented by menstrual diary
      scores at baseline (Higham score > 150), and at three, six, and 12 months after
      the procedure. Five patients withdrew prior to surgery and 50 patients were
      anaesthetized in each group. Two patients in the suction curettage group had
      their management converted to hysteroscopic ablation, one because of a large
      uterine cavity (> 12 mL) and one because of a submucous myoma. The ThermaChoice
      II system circulated the liquid within the silicone balloon for eight minutes at
      approximately 180 mmHg pressure and 87 degrees C. RESULTS: Participants' mean
      age, weight, and duration of menorrhagia were not significantly different between
      the groups. No safety issues related to the device were noted. At one year after
      ablation, the median reduction in Higham score was from 286 to 10 (96.5%) in the
      goserelin group (n = 47), and from 272 to 14 (94.9%) in the curettage group (n =
      45). The combined amenorrhea/hypomenorrhea rates (higham score 0 to 35),
      eumenorrhea rate (higham score 36 to 75) and menorrhagia rate (higham score > 75)
      were 85%, 9%, and 6% (goserelin), and 76%, 16%, 9% (curettage), respectively.
      Patients' reported self-assessment of dysmenorrhea was none (51%), mild (30%),
      moderate (10%), and severe (9%) in both groups. Patient satisfaction was 89% in
      the goserelin group and 95% in the curettage group. In the goserelin group, one
      patient had a hysterectomy for bleeding and two had repeat resectoscopic
      endometrial ablations, one for pain (hematometra) and one for pain and bleeding.
      In the curettage group, one patient had repeat resectoscopic ablation, one
      patient withdrew, and one requested hormone therapy. The overall success rates
      were 88% in the goserelin group and 89% in the curettage group. CONCLUSION: At
      one year after ThermaChoice II treatment, 88.5% of women had normal menstrual
      bleeding or less. There was a non-significant trend (a lower Higham score)
      towards superiority of goserelin therapy before ablation compared with curettage.

PMID- 21176308
TI  - Vaginal hysterectomy for the enlarged fibroid uterus: a report of 85 cases.
AB  - OBJECTIVE: To demonstrate that increased uterine size should not be a deterrent
      to the vaginal approach for performing hysterectomy. METHOD: We performed a
      retrospective study of the medical records pertaining to 2769 hysterectomies
      performed by a single surgeon. For this study, we reviewed the surgical details
      and outcome of 85 women who had a vaginal hysterectomy for a symptomatic fibroid
      uterus that was estimated to be equivalent in size to a uterus of between 10 and
      20 weeks' gestation. RESULTS: The vaginal approach for hysterectomy was
      successful in all 85 cases and complication rates were low. Sixteen women had
      additional adnexal surgery besides hysterectomy. In 52 cases, morcellation of the
      uterus was required. Average operating time was 60 minutes. CONCLUSION: Increased
      uterine size should not be an automatic deterrent to the vaginal approach for
      hysterectomy. Nevertheless, individual surgeons should perform such challenging
      procedures only if they are properly trained and are comfortable doing so. Some
      surgeons may choose not to perform hysterectomies using the vaginal approach.

PMID- 21176309
TI  - Postpartum hemorrhage in a Jehovah's Witness patient controlled with Tisseel,
      tranexamic acid, and recombinant factor VIIa.
AB  - BACKGROUND: The management of a patient refusing blood transfusion who
      subsequently experiences a severe postpartum hemorrhage is a particular clinical
      challenge. CASE: A 30-year-old nulliparous patient (who was a Jehovah's Witness)
      had labour induced for post-dates at 41+4 weeks' gestational age after an
      uncomplicated pregnancy. She delivered by Caesarean section for dystocia and
      suspected chorioamnionitis, and subsequently developed postpartum hemorrhage that
      required management with oxytocin, ergometrine, carboprost, uterine artery
      ligation, and Hayman compression sutures. The patient ultimately required two
      additional visits to the operating room, culminating in hysterectomy. Use of
      tranexamic acid, recombinant factor VIIa, and Tisseel was instrumental in halting
      the ongoing hemorrhage. CONCLUSION: Optimal management of a patient refusing
      administration of blood products requires a multidisciplinary approach as well as
      a combination of traditional and novel therapies.

PMID- 21176310
TI  - The "warfarin window" in pregnancy: the importance of half-life.
AB  - Anticoagulation therapy during pregnancy in women with prosthetic cardiac valves
      is a therapeutic challenge. The use of vitamin K antagonists such as warfarin
      during pregnancy carries the potential for serious risks to the fetus, especially
      if these drugs are administered during the first trimester or at term. Between 6
      and 12 weeks' gestation, fetal synthesis of proteins crucial for bone and
      cartilage formation may be impaired by warfarin, resulting in the well-defined
      "warfarin embryopathy." One of the most commonly suggested regimens involves the
      substitution of heparin for warfarin between 6 and 12 weeks' gestation to
      minimize the risk of warfarin embryopathy. Warfarin has a long half-life;
      following a single dose, the terminal elimination half-life is about one week,
      with a mean effective half-life of 40 hours. To date, all existing guidelines
      have ignored this long elimination half-life. If a policy of substituting heparin
      for warfarin between 6 and 12 weeks' gestation is followed, we suggest that
      substitution should begin at a much earlier gestational age. Substitution
      starting at 6 weeks' gestation may be too late to avoid embryopathy.

PMID- 21176311
TI  - Asymptomatic endometrial thickening.
AB  - OBJECTIVE: To formulate clinical recommendations for the assessment of
      endometrial thickening when it is found on ultrasound in a postmenopausal patient
      without bleeding. OUTCOMES: Ensure that women with asymptomatic thickening and
      endometrial polyps found on ultrasound are managed appropriately. EVIDENCE:
      Published literature was retrieved through searches of English language articles
      from the EMBASE, Cochrane, and PubMed databases for relevant peer-reviewed
      articles dating from 1970 to 2009, using appropriate controlled vocabulary (e.g.,
      "asymptomatic endometrial thickness," "endometrial cancer," "postmenopausal
      bleeding," "transvaginal ultrasonography," "endometrial biopsy" and "endometrial
      polyp"). 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 April 2010. 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 level of evidence was
      determined according to the criteria established by the Canadian Task Force on
      Preventative Health Care (Table). Recommendations are ranked according to this
      method. BENEFITS, HARMS, AND COSTS: It is anticipated that the adoption of these
      recommendations would save postmenopausal women unnecessary anxiety, pain, and
      risk of procedural complication. It is also expected to decrease the cost to the
      health system by eliminating unnecessary interventions.

PMID- 21176312
TI  - Vulvar burn: a complication of hysteroscopic endometrial ablation.

PMID- 21176313
TI  - Influence of oligohydramnios on preterm premature rupture of the membranes at 30
      to 36 weeks' gestation.
AB  - OBJECTIVE: to evaluate the influence of initial oligohydramnios on the prognosis
      of women with preterm premature rupture of the membranes (PPROM) at 30 to 36
      weeks' gestation. METHODS: the Royal Alexandra Hospital ultrasound database was
      used to identify singleton pregnancies at 30 to 36 weeks' gestation with an
      ultrasound performed for confirmed PPROM from January 1992 to December 2006.
      Records were linked to the electronic provincial delivery record to perform a
      retrospective cohort study comparing the outcomes of pregnancies with an initial
      amniotic fluid index (AFI) < 5 cm with the outcomes of pregnancies with an AFI of
      5 to 10 cm. Logistic and linear regression were used to analyze the association
      between binary outcome and explanatory variables. RESULTS: the maternal and
      perinatal outcomes of 438 pregnancies were analyzed. Univariate analysis
      suggested statistically significant associations between initial oligohydramnios
      and decreased latency (P < 0.001), increased histologically proven
      chorioamnionitis (P = 0.01), neonatal length of stay in hospital (P = 0.002), and
      NICU (P = 0.003); however, after controlling for confounding variables
      (gestational age at delivery, parity, presentation, and antenatal antibiotic and
      corticosteroid administration), only latency remained significant (P = 0.004). No
      association was found between initial oligohydramnios and any other outcomes
      assessed, including mode of delivery, postpartum endometritis, maternal length of
      stay, non-reassuring fetal status, and neonatal morbidity and mortality.
      CONCLUSION: initial oligohydramnios is associated with decreased latency in
      singleton pregnancies complicated by PPROM at 30 to 36 weeks' gestation; however,
      it does not appear to influence maternal or neonatal infectious morbidity, and it
      may not be useful to determine candidacy for expectant management or intentional
      delivery.

PMID- 21176314
TI  - The effectiveness of screening for hepatitis C in pregnancy.
AB  - OBJECTIVE: to determine the effectiveness of universal versus targeted screening
      for hepatitis C (HCV) during pregnancy at an urban health care centre. METHODS:
      we conducted a cross-sectional study of 653 pregnant women. Patients completed a
      demographic and standardized questionnaire identifying known risk factors for
      HCV. Patients then underwent blood testing for HCV antibodies. The effectiveness
      of screening based on risk factors was determined by comparing the number of
      women who screened positive for HCV risk factors with those who tested
      seropositive. RESULTS: of those who entered the study, 0.5% (3/645) tested
      positive for HCV. HCV risk factor screening showed that 72% answered "Yes" to one
      or more risk factors and 28% answered "No" to all risk factors. Answering "Yes"
      to any risk factor was not associated with testing positive for HCV antibodies (P
      > 0.05). Screening positive for a high severity risk factor (exposure to
      intravenous drug use or to the blood of an HCV-positive individual) was
      associated with testing positive for HCV antibodies (P = 0.002), but screening
      positive for a moderate or low severity risk factor was not (P > 0.05).
      CONCLUSION: during pregnancy, universal testing for HCV and testing based on the
      presence of any risk factors for HCV is not recommended. HCV testing based on the
      presence of high severity risk factors, however, may be warranted.

PMID- 21176315
TI  - Neighbourhood family income and adverse birth outcomes among singleton
      deliveries.
AB  - OBJECTIVE: to assess the association between neighbourhood family income and
      adverse birth outcomes. METHODS: we conducted a retrospective cohort study of 334
      231 singleton births during 2004 and 2006 based on the Niday Perinatal Database
      from Ontario. Median neighbourhood family incomes from the 2001 Canadian census
      were linked with the Niday Perinatal Database by dissemination areas. Generalized
      estimating equations were applied to estimate the odds ratios of adverse birth
      outcomes associated with lower neighbourhood income, with adjustment for maternal
      confounding variables at the individual level. RESULTS: compared with the highest
      neighbourhood income quintile, mothers from the lowest quintile were at increased
      risk of having small for gestational age neonates (OR 1.51; 95% CI 1.46 to 1.57),
      low birth weight (OR 1.43; 95% CI 1.36 to 1.50), preterm birth (OR 1.17; 95% CI
      1.12 to 1.23), low Apgar score (< 7) at five minutes (OR 1.32; 95% CI 1.21 to
      1.44), and stillbirth (OR 1.39; 95% CI 1.19 to 1.62). The risks of women from the
      lowest income quintiles delivering a macrosomic baby (OR 0.81; 95% CI 0.79 to
      0.84) or a large for gestational age baby (OR 0.82; 95% CI 0.80 to 0.85) were
      significantly decreased. No difference in risk of congenital anomaly was found
      among different income quintiles. CONCLUSION: a lower level of neighbourhood
      income is associated with increased risks of small for gestational age babies,
      low birth weight, preterm birth, low Apgar score at five minutes, and stillbirth.

PMID- 21176316
TI  - Ovarian cancer in the elderly patient: are we doing enough?
AB  - INTRODUCTION: ovarian cancer is deadly and frequently affects older patients. In
      the next 20 years, the number of patients over 65 will double, and cancer,
      including ovarian cancer, will increase in incidence. We wished to determine
      whether surgical morbidity, outcomes, and survival rates were worse in the older
      age group than in younger patients, and whether measuring serum CA 125 could be
      helpful in triaging patients for surgery. METHODS: we conducted a retrospective
      chart review of patients undergoing surgery for ovarian cancer in our institution
      from April 1996 to May 2006. A total of 127 patients met the inclusion criteria
      and were divided by age into two groups: patients aged under 70 and those aged 70
      or older. We used Fisher test, two-tailed Student t test, chi-square test, and
      Kaplan-Meyer statistical methods to obtain survival curves and to test hypotheses
      and probabilities. RESULTS: patients aged 70 and over were less likely to have
      stage I disease and to undergo optimal surgery. They also presented with more
      advanced disease, but this did not translate into a difference in survival rates.
      Serum CA 125 levels did not enable identification of older patients who would
      benefit from surgery. CONCLUSION: older patients with ovarian cancer did not have
      reduced survival rates compared to younger patients, but they were more likely to
      undergo suboptimal surgery and to have more advanced disease. Preoperative serum
      CA 125 measurements did not identify patients in the older age group for whom
      surgery would be optimal.

PMID- 21176317
TI  - Sonographic diagnosis of chronic abruption.
AB  - BACKGROUND: placental abruption is usually an acute event in which clinical
      decision-making overrides the need for ultrasound imaging. By contrast, chronic
      abruption may present with vague or even confusing clinical findings. We describe
      a case in which the diagnosis of chronic abruption was established by ultrasound
      and the findings directly influenced clinical care. CASE: a 30-year-old woman
      with asymptomatic preeclampsia was evaluated in our fetal medicine unit at 30
      weeks' gestation. Despite normal fetal monitoring, a large, retroplacental
      sonolucent area was noted on ultrasound. A planned Caesarean section was
      performed two days later, despite normal daily fetal monitoring, because the mass
      had increased in size. Placental pathology confirmed the diagnosis of chronic
      abruption. CONCLUSION: ultrasound may establish the diagnosis of a large chronic
      placental abruption that is relevant for clinical management.

PMID- 21176318
TI  - An unusual complication after vaginal hysterectomy.
AB  - BACKGROUND: uterovaginal prolapse is a common problem in older women, with
      significant economic and health implications. For the patient no longer desiring
      fertility or unwilling to undergo conservative management, the definitive
      treatment is a vaginal hysterectomy with simultaneous repair of anterior or
      posterior compartment defects if present. CASE: A 66-year-old postmenopausal
      woman with procidentia, cystocele, rectocele, and latent stress incontinence
      underwent vaginal hysterectomy, anterior and posterior colporrhaphy, and
      placement of a modified mid-urethral sling. Perioperatively she sustained a
      fracture of the pubic ramus that was not explained by perioperative events or her
      medical history. CONCLUSION: unusual and unexpected complications can occur after
      routine vaginal surgery in the older, postmenopausal population.

PMID- 21176319
TI  - Obstetrics and gynaecology as a career choice: a cohort study of canadian medical
      students.
AB  - OBJECTIVE: to describe the characteristics of medical students interested in
      obstetrics and gynaecology and to build a model that predicts which of these
      students will choose obstetrics and gynaecology as their career. STUDY DESIGN:
      students were surveyed in 2002, 2003, and 2004 at the commencement of their
      medical studies. Data were collected on career choice, attitudes to practice, and
      demographics at medical school entry and on career choice at medical school exit.
      RESULTS: three items present at entry to medical school were predictive of
      students ultimately choosing a career in obstetrics and gynaecology: having this
      career as one of their first three career choices at entry (having it as their
      first choice was the strongest predictor), being female, and desiring a narrow
      scope of practice. CONCLUSION: students choosing a career in obstetrics and
      gynaecology have attributes at medical school entry that differentiate them from
      students interested in other specialties. Identifying these attributes may guide
      education in and recruitment to obstetrics and gynaecology.

PMID- 21176321
TI  - Recurrent urinary tract infection.
AB  - OBJECTIVE: to provide an update of the definition, epidemiology, clinical
      presentation, investigation, treatment, and prevention of recurrent urinary tract
      infections in women. OPTIONS: continuous antibiotic prophylaxis, post-coital
      antibiotic prophylaxis, and acute self-treatment are all efficient alternatives
      to prevent recurrent urinary tract infection. Vaginal estrogen and cranberry
      juice can also be effective prophylaxis alternatives. EVIDENCE: a search of
      PubMed and The Cochrane Library for articles published in English identified the
      most relevant literature. Results were restricted to systematic reviews,
      randomized control trials/controlled clinical trials, and observational studies.
      There were no date restrictions. VALUES: this update is the consensus of the Sub
      Committee on Urogynaecology of the Society of Obstetricians and Gynaecologists of
      Canada. Recommendations were made according to the guidelines developed by the
      Canadian Task Force on Preventive Health Care (Table 1). OPTIONS: recurrent
      urinary tract infections need careful investigation and can be efficiently
      treated and prevented. Different prophylaxis options can be selected according to
      each patient's characteristics.

PMID- 21176323
TI  - Immediate postpartum pneumomediastinum.

PMID- 21176324
TI  - Sonographic maturation of the placenta at 30 to 34 weeks is not associated with
      second trimester markers of placental insufficiency in low-risk pregnancies.
AB  - OBJECTIVE: Advanced placental maturation (Grannum [G] grade 3) before term is
      associated with adverse perinatal outcomes associated with placental
      insufficiency. The nature and timing of the underlying pathology of this process
      is presently unclear. We hypothesized that advanced placental maturation at 30 to
      34 weeks' gestation is not associated with established second trimester markers
      of severe placental dysfunction. METHODS: In a cohort study of 1238 low-risk
      Caucasian women with singleton pregnancies who had sonographic assessment of
      placental maturation and fetal growth at 34 weeks, the results of maternal serum
      screening (MSS) and uterine artery Doppler (UtAD) flow studies at 16 weeks were
      related to adverse perinatal outcomes associated with placental insufficiency:
      antepartum hemorrhage, preeclampsia, preterm birth < 37 weeks, small for
      gestational age (< 10th percentile), or postnatal evidence of intrauterine growth
      restriction (IUGR; ponderal index < 5th percentile). RESULTS: G1 was found in 127
      women (10.3%), G2 was found in 18 women (1.5%), and no cases of G3 were observed.
      Advanced Grannum grading was significantly associated with IUGR (48 [4.4%] in G0,
      9 [7.1%] in G1, 5 [27.8%] in G2; P < 0.001), but was dependent on smoking status.
      IUGR was not predicted by abnormal MSS or abnormal UtAD findings at either the
      second or third trimester ultrasounds. CONCLUSION: G2 maturation at 30 to 34
      weeks' gestation is associated with mild IUGR at delivery in low-risk women and
      with smoking. IUGR was not predicted by either second or third trimester markers
      of severe placental dysfunction. Future studies directly observing the placenta
      in the late third trimester may aid the elusive diagnosis of "late-onset" mild
      IUGR.

PMID- 21176325
TI  - Maternal mortality and severe maternal morbidity surveillance in Canada.
AB  - The Canadian Perinatal Surveillance System has provided a comprehensive review of
      maternal mortality and severe maternal morbidity in Canada, and has identified
      several important limitations to existing national maternal data collection
      systems, including variability in the detail and quality of mortality data. The
      Canadian Perinatal Surveillance System report recommended the establishment of an
      ongoing national review and reporting system, as well as consistency in
      definitions and classifications of maternal mortality and severe maternal
      morbidity, in order to enhance surveillance of maternal mortality and severe
      maternal morbidity. Using review articles and studies that examined maternal
      mortality in general as opposed to maternal mortality associated with particular
      management strategies or conditions, maternal mortality and severe morbidity
      classifications, terminology, and comparative statistics were reviewed and
      employed to evaluate deficiencies in past and current methods of data collection
      and to seek solutions to address the need for enhanced and consistent national
      surveillance of maternal mortality and severe maternal morbidity in Canada.

PMID- 21176326
TI  - Maternal transdermal nitroglycerin use and early childhood development.
AB  - OBJECTIVE: Our randomized, double-blind, placebo-controlled trial of transdermal
      nitroglycerin (GTN) for preterm labour demonstrated a significant reduction in
      neonatal morbidity and mortality. The objective of this study was to evaluate
      developmental performance in the children born to women who participated in the
      GTN trial after one year and two years of follow-up. METHODS: The Ages and Stages
      Questionnaires (ASQ) were used for the assessments, and five domains of child
      development (communication, gross motor skills, fine motor skills, problem
      solving, and personal social skills) were evaluated. Supplementary analyses were
      performed after stratifying study subjects by gestational age at birth (< 28, 28
      to 32, 33 to 36, >= 37 weeks) or by defining study subjects as normal or abnormal
      using standard cut-offs. RESULTS: A total of 153 infants born to women who
      participated in the GTN trial were included in the initial follow-up. Among them,
      111 (72.5%) children (55 in the GTN arm and 56 in the placebo arm) at 12 months
      of age and 83 (54.2%) children (42 in the GTN arm and 41 in the placebo arm) at
      24 months of age completed the full ASQ. There were no differences in ASQ total
      score and five subscores between the GTN arm and the placebo arm at the one-year
      and two-year follow-up evaluations, in overall study subjects, or after
      stratifying study subjects by gestational age. A trend towards reduced
      abnormalities in the GTN arm at the two-year follow-up was observed, although
      there was no statistical significance. CONCLUSION: Maternal GTN use for preterm
      labour had no impact on children's long-term development, but larger studies are
      needed to confirm the preliminary findings of this study.

PMID- 21176327
TI  - Reproductive assistance, emotional health, obesity, and time to pregnancy among
      women under 35 years of age.
AB  - OBJECTIVE: The primary objective of this analysis was to describe demographic,
      physical, lifestyle, and psychosocial factors related to becoming pregnant in six
      months or less among women under 35 years of age who delivered a live-born
      infant. We also wished to determine the relative impact of these factors on time
      to pregnancy, regardless of use of fertility treatment. METHODS: Between July
      2002 and September 2003, we conducted a survey by telephone interview of 1044
      randomly selected women who had recently delivered their first live-born infant
      in Calgary or Edmonton, Alberta. RESULTS: Among 575 women who were less than 35
      years of age when they began trying to conceive and who ultimately delivered a
      live-born infant, the most significant predictors of taking more than six months
      to conceive included being overweight or obese (hazard ratio [HR] 1.34; 95% CI
      1.05 to 1.72), having a history of pregnancy complications (HR 1.42; 95% CI 1.02
      to 1.99), and having fair or poor self-rated emotional health six months prior to
      pregnancy (HR 2.02; 95% CI 1.27 to 3.22). The influence of BMI and emotional
      health on time to conception did not change substantially when women who had
      assistance with conception (16% of the sample) were excluded from the analysis.
      CONCLUSION: Among those who ultimately carry a pregnancy to delivery, the
      relationship between high BMI or poor emotional health and delays in conception
      was evident among women who conceived with or without assistance. Public health
      strategies that help women to achieve optimal body weight and address issues of
      emotional health may reduce the need for assisted reproduction.

PMID- 21176328
TI  - Long-term efficacy of pelvic floor muscle rehabilitation for older women with
      urinary incontinence.
AB  - OBJECTIVES: To determine the efficacy of pelvic floor muscle (PFM) rehabilitation
      for elderly women with urinary incontinence after five years of follow-up, and to
      assess the adherence to PFM exercises five years after physiotherapy. METHODS: We
      conducted a retrospective chart review of women >= 60 years old who underwent PFM
      physiotherapy for urinary incontinence between September 1999 and February 2004.
      PFM rehabilitation techniques were taught to patients by a certified
      physiotherapist. The mean number of sessions was eight. Telephone surveys were
      conducted at two months, six months, and one to five years after physiotherapy.
      Objective data on the efficacy of treatment (number of voids, incontinence, use
      of pads) and on adherence to PFM exercises were collected using a uniform grid.
      Data were used to determine the continence status at follow-up and compared with
      the data collected at the end of the PFM training sessions (improved, maintained,
      or deteriorated). RESULTS: Of 89 older women (mean age 70 years; range 60 to 81)
      treated during the study period, 40 were followed up to five years and were
      suitable for analysis. At five years of follow-up, 27.5% had improved, 57.5%
      remained stable, and 15% had deteriorated compared with their post-treatment
      continence status. Twenty-nine patients (72.5%) were continuing their PFM
      exercises, and 42.5% were performing the exercises daily. All adherent patients
      had "improved" or "stable" status after five years versus 45.5% of non-adherent
      patients (P < 0.05). CONCLUSION: Pelvic floor muscle rehabilitation for urinary
      incontinence remains highly effective for up to five years in older women. Most
      women continue to perform PFM exercises five years after completing their
      physiotherapy education sessions.

PMID- 21176329
TI  - Rituximab for management of refractory pregnancy-associated immune
      thrombocytopenic purpura.
AB  - BACKGROUND: Rituximab is a novel therapy for immune thrombocytopenic purpura
      (ITP); however, information about its safety in pregnancy is limited. This case
      illustrates the successful use of rituximab to treat pregnancy-associated ITP.
      CASE: A 34-year-old woman presented with severe ITP at 23 weeks' gestation.
      Standard treatment with corticosteroids, intravenous immune globulin, and
      splenectomy failed to raise the platelet count. Due to ongoing bleeding,
      rituximab was given in the 26th week of pregnancy. The platelet count rose to
      over 100 * 10(9)/L after four weeks. The neonatal B-lymphocyte count normalized
      at four months after delivery. There were no neonatal complications of rituximab
      therapy. CONCLUSION: Rituximab may be safe for use in treating pregnancy
      associated ITP. This case highlights the need to investigate further the safety
      and efficacy of rituximab in pregnancy.

PMID- 21176330
TI  - Laparoscopic internal iliac artery ligation for postpartum spontaneous
      hemoperitoneum.
AB  - BACKGROUND: Spontaneous hemoperitoneum in pregnancy or the postpartum period is
      an uncommon but potentially life-threatening complication. CASE: A 29-year-old
      woman presented with severe abdominal pain, decreased consciousness, and a
      reduced hemoglobin level three days after an uneventful spontaneous vaginal
      delivery. Initial ultrasound and CT imaging showed significant hemoperitoneum
      with no identifiable cause. Laparoscopic surgery was performed, during which
      bleeding from the left uterine artery was identified and resolved with
      laparoscopic internal iliac artery ligation. Concomitant cul-de-sac obliteration
      and adhesions secondary to decidualized endometriosis were found. CONCLUSION:
      Decidualized endometriosis is a possible etiologic factor in spontaneous
      hemoperitoneum. Prompt diagnosis and treatment are critical for improving
      outcomes. When surgical intervention is indicated, a laparoscopic approach should
      be considered because of its minimally invasive nature and shorter recovery time.

PMID- 21176331
TI  - The obstetrics and gynaecology resident as teacher.
AB  - In this article we discuss the role residents play in the clinical training and
      evaluation of medical students. A literature search was performed to identify
      articles dealing with research, curriculum, and the evaluation of residents as
      teachers. We summarize the importance of resident educators and the need to
      provide appropriate resources for house staff in this role, and we review
      evidence-based literature in the area of residents as teachers. Specific
      attention is given to the unique circumstances of the obstetrics and gynaecology
      resident, who is often faced with teaching in an emotionally charged and stress
      filled environment. We present examples of curricula for residents as teachers
      and describe barriers to their implementation and evaluation.

PMID- 21176332
TI  - SOGC clinical practice guideline. No. 252, December 2010. Oral contraceptives and
      the risk of venous thromboembolism: an update.
AB  - OBJECTIVE: To provide current and emerging evidence on oral contraceptives and
      the risk of venous thromboembolism. EVIDENCE: Articles published in English from
      2005 were retrieved through searches of PubMed and Medline, using the following
      terms: venous thromboembolism, VTE, contraception, oral contraceptives, hormonal
      contraception. 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 May 2010. 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 was
      rated using the criteria described by the Canadian Task Force on Preventive
      Health Care (Table). SUMMARY STATEMENTS: 1. Modern oral contraceptives offer
      highly effective contraception and a range of non-contraceptive benefits. (I) 2.
      Venous thromboembolism, although rare, remains one of the serious adverse
      consequences of hormonal contraception. Best evidence indicates that venous
      thromboembolism rates in non-users of reproductive age approximate 4-5/10 000
      women per year; rates in oral contraceptive users are in the range of 9-10/10 000
      women per year. For comparison, venous thromboembolism rates in pregnancy
      approach 29/10 000 overall and may reach 300-400/10 000 in the immediate
      postpartum period. (II-1) 3. Research demonstrates that oral contraceptives with
      <= 35 ug of ethinyl estradiol carry a lower risk of venous thromboembolism than
      oral contraceptives with 50 ug. (II-2) Although preliminary data suggest a
      possible further reduction in venous thromboembolism with oral contraceptives
      with < 35 ug ethinyl estradiol, robust data to support this conclusion are
      presently lacking. 4. Recent contradictory evidence and the ensuing media
      coverage of the venous thromboembolism risk attributed to the progestin component
      of certain newer oral contraceptive products have led to fear and confusion about
      the safety of oral contraceptives in general and drospirenone-containing oral
      contraceptives in particular. "Pill scares" of this nature have occurred in the
      past, with panic stopping of the pill, increased rates of unplanned pregnancy,
      and no subsequent decrease in venous thromboembolism rates. (II-3) 5. Two high
      quality research studies that addressed the venous thromboembolism risk
      associated with various oral contraceptives found comparable venous
      thromboembolism rates with drospirenone-containing oral contraceptives and other
      approved products. (II-1) 6. Two reports suggesting an increased risk of venous
      thromboembolism with drospirenone-containing oral contraceptives have significant
      methodological flaws that render their conclusions suspect. It seems likely that
      residual confounding could have distorted both the results and the conclusions of
      these reports. (II-3).

PMID- 21176334
TI  - [Clinical and molecular biologic characteristics of 36 cases of leukemia with
      11q23/mll].
AB  - This study was aimed to analyze the clinical and cytogenetic characteristics of
      acute leukemia with 11q23/mll rearrangement and explore the reasonable
      therapeutic principles. Characteristics in general situation, morphology,
      immunology, molecular biology, cytogenetics, treatment and overall survival of 36
      cases of acute leukemias with mll gene rearrangement were studied and analyzed.
      The results showed that 36 cases with mll gene rearrangement were found positive
      (7.2%) in 494 patients with acute leukemia. Among the 36 cases of mll
      rearrangement positive, 32 cases were diagnosed as acute myeloid leukemia (AML)
      with myeloid antigen expression, of which 5 cases expressed lymphoblastic
      differentiation antigen; 4 cases were classified as B-lineage acute lymphoblastic
      leukemia (ALL), of which non-lineage myeloid expression pattern were found in 3
      cases. In 29 out of 36 cases (80%) the clonal chromosomal aberration were
      detected, of which chromosome 11 aberration were observed in 22 cases. All
      patients received chemotherapy with a total response rate of 47.2%. Of the
      responded patients, 10 cases relapsed within 6 months, with a recurrence rate of
      40%; 9 cases received hematopoietic stem cell transplantation (HSCT), 7 cases of
      which survived after transplantation. The median survival time of 36 cases was 16
      months (range 2 - 46) and their 2-year overall survival rate was 41.4%. The 2
      year overall survival rate of 9 patients who received HSCT was 87.5%. It is
      concluded that acute leukemia patients with mll gene rearrangement show poor
      response to chemotherapy, high recurrence rate and poor prognosis. Hematopoietic
      stem cell transplantation may be a reasonable treatment principle to improve
      these patients' survival situation.

PMID- 21176335
TI  - [FMS-like tyrosine kinase 3 gene mutation in acute myeloid leukemia detected by
      denaturing PAGE and its clinical significance].
AB  - The aim of this study was to analyze the frequency of flt3 length mutation (flt3
      LM) in de novo acute myeloid leukemia patients and the relationship between flt3
      LM and chromosome alterations, FAB subgroups, as well as efficiency of therapy.
      Genomic DNA was amplified by PCR; 2% agarose gel or 8% denaturing PAGE were used
      to detect the length mutation of flt3 gene in 99 de novo acute myeloid leukemia
      patients; karyotyping in 72 AML patients was performed by G banding technique.
      The results showed that the flt3-LM was detected in 20.2% (20/99) patients by
      agarose gel electrophoresis, and in 29.9% (29/99) by denaturing PAGE. The flt3-LM
      was not detected in M(0) (only one patient was available), but flt3-LM occurrence
      in AML subtypes was as follow: in M(2) (9/30), M(3) (6/27), M(4) (4/14), M(5)
      (7/19), M(6) (3/8) respectively. flt3-LM in patients with normal karyotypes
      (39.13%) was more prevalent as compared with patients of abnormal karyotype
      (24.49%), but there was no statistical difference (p > 0.05). The complete
      remission (CR) rate in flt3-LM positive patients (36.36%) was lower than that in
      flt3-LM negative patients (62.75%) in the 73 patients (p < 0.05) whose karyotypic
      detection was performed. The distributions of flt3-LM were observed in 8 out of
      40 CR patients, 8 out of 21 PR patients, and 6 out of 12 NR patients. It is
      concluded that the denaturing PAGE is more sensitive and reliable to detect the
      flt3-LM. The flt3 mutation represents a common genetic abnormality in AML
      patients, and the flt3-LM is associated with lower CR rate.

PMID- 21176336
TI  - [Alteration of methylation status of death-associated protein kinase (dapk) gene
      promoter in patients with acute myeloid leukemia].
AB  - This study was purposed to analyze the methylation status of death-associated
      protein kinase (dapk) gene promoter in Chinese patients with acute myeloid
      leukemia (AML) and its relationship with clinical features. The methylation
      specific PCR (MSP) technique was used to detect dapk promoter methylation in bone
      marrow samples from 112 cases of AML. The results indicated that gene dapk
      promoter hypermethylation was detected in 82 cases (73.2%), but not in 13 control
      group. There was no correlation of dapk gene hypermethylation with sex, age, WBC
      counts, platelet counts, hematologic parameters, chromosomal abnormalities and
      different subtypes of AML patients. It is concluded that dapk gene
      hypermethylation may be a common molecular event in AML.

PMID- 21176337
TI  - Simultaneous analysis of telomere length and cell surface antigen in leukemia by
      multicolor Flow-FISH.
AB  - This study was purposed to explore the feasibility of simultaneous analysis of
      telomere length and cell surface antigen by multicolor Flow-FISH to assess
      minimal residual disease (MRD) in leukemia. The telomere length in 34 leukemia
      patients versus 20 normal controls was compared by using Flow-FISH, and the
      relationship between telomere length and therapeutic effect and prognosis was
      analyzed preliminarily. As for those patients with follow-up samples, the changes
      of telomere length combined with surface antigen in different courses of disease
      were observed by multicolor Flow-FISH. The results indicated that the telomere
      length of de novo patients was significantly shorter than that of controls except
      the patients in chronic myeloid leukemia-chronic phase (CML-CP). The shorter
      telomere, the lower complete remission (CR) rates were observed in acute leukemia
      cases and the shorter duration of CP before onset of blast phase (BP) occurred in
      CML cases. The acute leukemia patients showed longer telomere and fewer cells
      expressed the related antigen after CR. The telomere length of cases with
      continued CR remained at normal level during remission, and there was no
      increased expression of the specific antigen. However, the telomere of relapsed
      cases shortened again after relapse with elevated specific antigen expression. In
      the relapsed cases, the telomere of related antigen positive cells shortened
      ahead of telomere length change of the whole cells and morphologic change of bone
      marrow cells. It is concluded that analysis of telomere length by flow-FISH
      manifests the significance for monitoring disease conditions, estimating
      prognosis and guiding therapy in all kinds of leukemia. The simultaneous analysis
      of telomere length and cell surface antigen by multicolor flow-FISH may monitor
      abnormal clone or clonal evolution to predict recurrence more sensitively and
      specifically, and may provide a promising and widely applicable method for
      monitoring MRD in leukemia.

PMID- 21176338
TI  - [Methylation status of id4 gene promoter in patients with chronic myeloid
      leukemia].
AB  - This study was purposed to investigate the methylation status of id4 gene
      promoter in patients with chronic myeloid leukemia (CML) and explore the
      relationship between methylation of the id4 gene and progress of CML. The
      methylation status of id4 gene in 48 chronic myeloid leukemia patients and 10
      healthy individuals was detected by using methylation-specific polymerase chain
      reaction (MS-PCR). The results showed that id4 gene was unmethylated in bone
      marrow samples from both healthy individuals and CML patients in chronic phase
      (CP). The rate of id4 gene methylation in both CML patients in accelerated phase
      (AP) and blast crisis (BC) was 66%, and was higher than those of CML patients in
      CP phase. There was significant difference between them (p < 0.05). In one CML
      patient who received a serial observations, the status of id4 was unmethylated in
      CP, but it was methylated in AP and BC phase. It is concluded that the id4 gene
      in CML patients is unmethylated in CP, while it is methylated in AP or BC. The
      detection of id4 gene methylation status may be useful for monitoring disease
      advance in CML and may be used as a marker of disease progression in CML.

PMID- 21176339
TI  - [Immunophenotype characteristics and prognosis of acute leukemia patients with
      cross expressing lymphoid and myeloid lineage associated antigens].
AB  - The aim of study was to investigate the immunophenotype characteristics and
      prognosis of acute leukemia patients with cross-expressing lymphoid and myeloid
      lineage-associated antigens. The immunophenotypes of leukemic cells were examined
      by using flow cytometry. All patients were classified into several groups
      according to FAB subtypes and immunophenotyping. The cross-expressed antigens
      analyzed for AML included CD2, CD7, CD19, CD56 and other co-expressed lymphoid
      antigens. The myeloid antigens analyzed for ALL included CD13 and co-expressed
      CD13/CD33. ALL and AML patients without expression of cross-expressing antigens
      were selected as control. Complete remission (CR) ratio and relapse-free survival
      (RFS) of patients in all groups were compared. The results indicated that among
      161 patients analyzed, 91 cases of AML with cross-expressing lymphoid and myeloid
      antigens included that 24 cases of AML expressed lymphoid surface marker-CD7,
      namely CD7(+) AML, 14 cases of AML only expressed lymphoid surface marker-CD19,
      namely CD19(+) AML, 8 cases of AML expressed lymphoid surface marker-CD2
      (including CD2/CD19 co-expressed), namely CD2(+) AML, 10 cases of AML expressed
      lymphoid surface marker-CD56 (including CD56/CD19 or CD56/CD2 co-expressed),
      namely CD56(+) AML, 16 cases of AML expressed two or more lymphoid surface
      markers, namely Ly >= 2(+) AML, 9 cases of ALL expressed myeloid surface markers
      CD13, namely CD13(+) ALL, 10 cases of ALL expressed myeloid surface markers CD13
      and CD33, namely CD13/CD33(+) ALL. 29 cases of ALL did not expressed myeloid
      surface markers, namely My(-) ALL, and 41 case of AML did not expressed lymphoid
      surface markers, namely Ly(-) AML. CR ratio and RFS of Ly >= 2(+) AML patients
      were lower than those of Ly(-) AML patients. RFS of CD56(+) AML patients was
      lower, but CR ratio had no significant difference, when compared with Ly(-) AML
      patients. CR ratio and RFS of other AML patients with cross-expressing antigens
      had no significant difference when compared with Ly(-) AML patients. CR ratio and
      RFS of CD13(+) ALL and CD13/CD33(+) ALL patients had no significant difference
      when compared with My(-) ALL patients. It is concluded that the importance of
      cross-expressing antigens for prognosis of patients should be analyzed
      concretely. CD56(+) AML and Ly >= 2(+) AML have bad prognosis, while other cross
      expressed lymphoid and myeloid lineage-associated antigens have no impact on
      prognosis of acute leukemia patients.

PMID- 21176340
TI  - [Immunophenotypic analysis of acute myeloid leukemia with t(8;21)].
AB  - This study was aimed to investigate laboratorial characteristics of
      immunophenotyping and concurrent karyotypic aberrations in acute myeloid leukemia
      with t(8;21)(q22;q22). A total number of 47 AML patients with t(8;21) were
      enrolled in this study and immunophenotypic antigens were detected by
      multiparameter flow cytometry. The results indicated that the additional
      karyotypic aberrations were found in 21 out of 47 AML patients with t(8;21)
      (q22;q22 (44.68%), single karyotypic aberration was observed in 26 out of 47 AML
      patients with t(8;21) (q22;q22) (55.32%). The positive rate of stem/progenitor
      cell markers of CD34, CD117 and HLA-DR were 87.2%, 97.9% and 95.7% respectively.
      Myeloid markers of CD13 and CD33 were 93.6% and 87.2%, and there were nearly no
      expression of T lineage antigens (CD2, CD3, CD5 and CD7) detected in t(8;21)-AML.
      CD19, one of a pan-B markers was found in 66.0% of all 47 t(8;21)-AML patients as
      well as CD56(66.7%), which was significant higher than other B lineage antigens
      (CD20 and CD22). It is concluded that AML with t(8;21) displays an exclusive
      immunophenotyping with significantly high expression of CD19 and CD56 as well as
      precursor cell markers (CD34, CD117 and HLA-DR) and combination detection of
      CD34/CD19/CD56 may become a predictive indicator of t(8;21) (q22;q22) cytogenetic
      abnormality.

PMID- 21176341
TI  - [april mRNA expression in newly diagnosed leukemia patients].
AB  - This study was aimed to quantitatively detect the levels of april mRNA expression
      in leukemia patients so as to provide theoretical basis for the target therapy
      directing at april in leukemia. Real time fluorescent quantitative PCR was used
      to detect the relative expression level of april mRNA in newly diagnosed leukemia
      patients and to analyze the changes of its expression level in various type of
      leukemia. The results showed that the april mRNA expression level in acute
      leukemia (AL) patients was significantly higher than that in normal controls,
      there was statistical difference between them (p < 0.05); april mRNA expression
      level in acute myeloid leukemia (AML) patients was significantly higher than that
      in normal controls (p < 0.05) and positively correlated with white blood cell
      count >= 20.0 * 10(9)/L (p < 0.05), but not related with extramedullary
      infiltration and the expression of CD34. Except for acute promyelocytic leukemia
      (APL), april mRNA expression level was negatively correlated with sensitivity of
      patients to chemotherapy. april mRNA expression levels in acute lymphoid leukemia
      (ALL) and chronic myeloid leukemia (CML) patients were not higher than that in
      normal controls, there was no statistical difference between them (p > 0.05). It
      is concluded that april gene overexpression exits in AML patients. APRIL protein
      produced by AML cells probably plays an important role in abnormal proliferation
      and drug-resistance of AML cells.

PMID- 21176342
TI  - [Expression of angiotensin-II type 1 receptor at1 mRNA in myeloid leukemia].
AB  - This study was aimed to explore the expression level of angiotensin-II type 1
      receptor (AT1) mRNA in bone marrow of myeloid leukemic patients, and its
      correlation with the proportion of leukemia cells in samples and Hb, WBC, Plt
      counting in peripheral blood. 51 samples, including 36 AML, 7 CML, and 8 samples
      of non-malignant hematological diseases as control group were collected. The
      expression of at1 mRNA was detected by real time-PCR; the expression levels of
      at1 gene in AML and CML groups were relatively quantitatively analyzed by using
      2(-DeltaDeltaCT) and were compared with control group. The results showed that
      the expression levels of at1 mRNA in AML, CML and control groups were 0.038 +/-
      0.076, 0.033 +/- 0.039, 0.281 +/- 0.366, respectively. at1 gene expression in the
      myeloid leukemic group was significantly lower than that in the control group.
      The expression level of at1 mRNA in AML was negatively correlated with the
      proportion of leukemia cells and positively with Hb level in peripheral blood. It
      is concluded that at1 gene may play a minor role in leukaemogenesis, however, may
      promote erythropoiesis.

PMID- 21176343
TI  - [Lysophosphatidic acid acyltransferase beta gene expression in newly diagnosed
      leukemia patients].
AB  - This study was aimed to quantitatively detect the expression level of
      lysophosphatide acid acyltransferase beta (lpaat beta) mRNA in leukemia patients
      so as to provide theoretical basis for the target therapy of lpaat beta in
      leukemia. Real-time fluorescently quantitative PCR was used to detect the
      relative expression level of lpaat beta mRNA to analyze its expression change in
      various type of leukemia. The results showed that the lpaat beta mRNA expression
      level in acute leukemia (AL) patients was significantly higher than that in
      normal controls (p < 0.05); lpaat beta mRNA expression level in acute myeloid
      leukemia (AML) patients was significantly higher than that in normal controls (p
      < 0.05) and was positively correlated with white blood cell count (>= 20.0 *
      10(9)/L) (p < 0.05) and CD34 expression level of leukemia, but was not related
      with extramedullary infiltration. Except for acute promyelocytic leukemia (APL),
      the lpaat beta mRNA expression level was negatively correlated with chemotherapy
      sensitivity in chronic myeloid leukemia (AML) patients. lpaat beta mRNA
      expression level in chronic myeloid leukemia (CML) patients was significantly
      higher than that in normal controls (p < 0.05). lpaat beta mRNA expression level
      in acute lymphoid leukemia (ALL) patients was not higher than that in normal
      controls (p > 0.05). It is concluded that the lpaat beta gene overexpression
      exists in both AML and CML patients. lpaat beta produced by AML cells probably
      plays an important role in abnormal proliferation and drug-resistance of AML
      cells.

PMID- 21176344
TI  - [Expression of pituitary tumor transforming gene in patients with AML].
AB  - The aim of study was to explore the expression of pituitary tumor-transforming
      gene (pttg) in acute myeloid leukemia (AML) and its relationship with the
      pathogenesis of AML, simultaneously to investigate the difference of the pttg
      expression among AML different subtypes. The expressions of pttg mRNA were
      quantitatively detected by real-time fluorescence quantitative polymerase chain
      reaction (real-time PCR) in bone marrow from 47 patients with AML and 28 normal
      controls. The results indicated that the expression of pttg mRNA was
      significantly higher in AML patients [(1.1323 +/- 1.3934) * 10(5)] than that in
      normal controls [(4.5766 +/- 1.1817) * 10(3)] (p < 0.05). The expression of pttg
      mRNA was higher in M(3) patients than that in other AML subtypes, such as M(1),
      M(2), M(4), M(5). It is concluded that the overexpression of pttg may be related
      to the pathogenesis and progression of AML, in which the overexpression of pttg
      may be more intimately related to the pathogenesis and progression of M(3). This
      study provides a new idea to research the pathogenesis and targeted gene therapy
      of AML.

PMID- 21176345
TI  - [Relationship between polymorphisms of myeloperoxidase gene and susceptibility of
      acute leukemia in Chinese Gansu population].
AB  - This study was aimed to explore the relationship between gene polymorphisms of
      myeloperoxidase (MPO) and the susceptibility of acute leukemia in Chinese Gansu
      population. G463A mutation of mpo gene was analyzed by polymerase chain reaction
      ligase detection reaction (PCR-LDR) in 100 normal individuals (control group) and
      100 patients with acute leukemia (AL group). The results showed that the a allele
      genotype and ga/aa genotype of mpo gene occurred more frequently in control group
      (28% and 54%) than those in AL group (19% and 31%) (p < 0.05). The AL risk for
      controls was decreased by 0.383-fold, compared with the individuals with gg
      genotype (95%CI = 0.215 - 0.682, p < 0.01). By further stratified analysis, the
      ga/aa genotype of mpo gene occurred more frequently in control group (54%) than
      those in AML group (28.2%) (p < 0.01). AML risk (95%CI = 0.157 - 0.546, p < 0.01)
      in the controls was decreased by 0.346-fold compared with the individual with gg
      genotype, however, the acute lymphoblastic leukemia (ALL) showed no significant
      difference from control group in the incidence of the allele a genotype and ga/aa
      genotype of mpo gene. It is concluded that mpo gene polymorphism is associated
      with susceptibility of acute myeloid leukemia in Chinese Gansu population. The
      risk of AML decreases in the persons carrying a allele, but mpo gene polymorphism
      is not associated with susceptibility of acute lymphoblastic leukemia.

PMID- 21176346
TI  - [Synergistic killing effect of the conditionally replicating adenoviruses
      carrying programmed cell death 5 gene and etoposide on K562 cells].
AB  - The expression levels of programmed cell death 5 (PDCD5) are down-regulated in
      many malignancies. SG611-pdcd5, a recombinant conditionally replicative
      adenovirus carrying pdcd5 gene expression cassette, can evidently kill the
      leukemic cells and protect selectively the normal cells. The purpose of this
      study was to investigate the synergistic killing effect of SG611-pdcd5 and low
      dose etoposide (VP-16) on K562 cells. K562 cells were treated with different
      concentrations of VP-16 or different multiplicities of infection (MOI) of SG611
      pdcd5. After 48 hours of incubation the cell viability was determined by using
      MTT assay. The results showed that the cell viability of SG611-pdcd5 (MOI = 40)
      plus VP-16 (0.5 ug/ml) group significantly decreased as compared with single
      SG611-pdcd5 (MOI = 40) treatment group or single VP-16(0.5 ug/ml) treatment group
      (42.00 +/- 5.75% vs 59.45 +/- 4.12%; 42.00 +/- 5.75% vs 82.91 +/- 3.41%,
      respectively, both p < 0.05). The synergistic killing effect of SG611-pdcd5 plus
      VP-16 was higher than that of PDCD5 protein plus VP-16 or that of non-replicating
      adenovirus carrying pdcd5 (Ad-pdcd5) plus VP-16 (both p < 0.05). The cell
      viability of VP-16 (4.0 ug/ml) plus SG611-pdcd5 (MOI = 40) group, VP-16 (4.0
      ug/ml) plus proPDCD5 (40 ug/ml) group and VP-16 (4.0 ug/ml) plus Ad-pdcd5 (MOI =
      80) group was 37.09 +/- 1.89%, 52.36 +/- 1.64% and 73.64 +/- 4.33%, respectively.
      It is concluded that SG611-pdcd5 can promote K562 cell death induced by low-dose
      VP-16. The combination of SG611-pdcd5 and VP-16 can enhance the killing effect on
      leukemic cells.

PMID- 21176347
TI  - [Effect of acetyl-11-keto-beta-boswellic acid on proliferation, apoptosis and
      cell cycle of human acute myeloid leukemia cell line HL-60].
AB  - The aim of this study was to investigate the effect of 3-O-acetyl-11-keto-beta
      boswellic acid (AKBA) on the proliferation, apoptosis and cell cycle of human
      acute myeloid leukemia (AML) cell line HL-60. HL-60 cells were treated by AKBA at
      various concentrations. The inhibitory effects of AKBA on the proliferation of HL
      60 were analyzed by MTT assay. Morphologic changes of HL-60 cells were observed
      by fluorescence microscopy with Hochest33342 staining. Cell apoptosis rate was
      determined by flow cytometry with Annexin-V-FITC/PI double staining. The cell
      cycle was measured by flow cytometry with PI staining. The results showed that
      AKBA inhibited the proliferation of HL-60 and the apoptosis rate of HL-60 cells
      was gradually enhanced when AKBA dose increased. AKBA changed the cell cycle of
      HL-60, resulting in cell increase at G(1) phase and decrease at S phase. It is
      concluded that the AKBA has anti-proliferation and apoptosis-inducing effects on
      HL-60 cells, that seems a promising therapeutical approach for AML.

PMID- 21176348
TI  - [Effect of valproic acid on apoptosis of leukemia HL-60 cells and expression of h
      tert gene].
AB  - This study was aimed to clarify whether valproic acid (VPA) induces apoptosis of
      leukemia HL-60 cell line and its possible mechanism. The effect of different
      concentrations and treatment time of VPA on HL-60 cell proliferation was assayed
      by cytotoxicity test (CCK-8 method) and fluorescence microscopy, and flow
      cytometry was used to detect cell apoptosis. The expressions of telomerase
      subunit h-tert mRNA and apoptosis-related protein as well as caspase-3 activity
      were detected by real time-quantitative PCR, Western blot and ELISA respectively.
      The results indicated that VPA inhibited proliferation of HL-60 cells and induced
      cell apoptosis in a dose dependent manner (r = -0.87). The expressions of anti
      apoptotic protein BCL-2 and h-tert mRNA were significantly decreased while the
      pro-apoptotic protein BAX and caspase-3 activity increased after treatment with
      VPA. The apoptosis rate of HL-60 cell was negatively correlated with expression
      of h-tert mRNA. It is concluded that VPA can inhibit leukemia HL-60 cell
      proliferation and induce apoptosis. The VPA displays anti-leukemia activity
      possibly through reducing h-tert mRNA and BCL-2 protein expression, increasing
      BAX expression and activity of caspase-3.

PMID- 21176349
TI  - [5-azacytidine suppresses K562 cell line proliferation by down-regulation of miR
      17-19b].
AB  - The aim of the research was to ascertain different expression levels of miRNA-17
      19b in different cell lines and to observe the changes of miR-17-19b expression
      in the cell line K562 with high expression level of miR-17-19b after 5
      azacytidine (5-aza) treatment. Total RNA was extracted from K562, HL-60, NB-4 and
      HeLa cell lines, white blood cells of peripheral blood from patient with chronic
      myeloid leukemia (CML) and mobilized white blood cells of peripheral blood from
      normal persons, respectively. Total RNA was polyadenylated by poly (A)
      polymerases and the expressions of miR-17-19b in the cell lines and the above
      mentioned cells were detected by SYBR-green real-time PCR. The K562 cell line was
      treated with 2.5 umol/L 5-aza for 24, 48 and 72 hours, then were collected at 96
      hours. The changes of miR-17-19b expression were determined by real-time PCR
      after 5-aza treatment. K562 cell line proliferation was observed after inhibition
      of miR-19a function. The results showed that the expression levels of miRNA-17
      19b in K562 cells and white blood cells of peripheral blood from CML patients
      were higher than those in mobilized white blood cells of peripheral blood from
      normal person. The expression level of miR-17-19b in K562 cells with high
      expression of miR-17-19b was down-regulated after 5-aza treatment. The
      proliferation of K562 cells was inhibited through suppression of miR-19a
      function. It is concluded that expression level of miR-17-19b is higher in K562
      cell line and white blood cells of peripheral blood from CML patients than that
      in white blood cells of peripheral blood from normal person. Expression of miR-17
      19b is inhibited in K562 cell line after 5-aza treatment. Inhibition of miR-19a
      in vitro can suppress the proliferation of K562 cell line.

PMID- 21176350
TI  - [Inhibition of evi1 expression by siRNA in HEL cell line].
AB  - The aim of study was to investigate the inhibitory effect of small interfering
      RNA on evi1 gene expression and biological characteristics in HEL cells and its
      mechanism. 3 siRNA (siRNA-1, siRNA-2, siRNA-3) specific for evi1 gene were
      synthesized and transfected into HEL cells in vitro. Experiments were divided
      into test and control groups. MTT method was used to assay the inhibitory effect
      of siRNA on cell proliferation; semiquantitative RT-PCR was used to detect the
      expression of evi1 gene mRNA; the cell viability was determined by trypan blue
      dye test; the change of cell cycle and apoptosis of cells were analyzed by flow
      cytometry. The results showed that siRNA-1 had strongest effect, and inhibitory
      effect was most obvious at 48 hours after transfection. When the concentration of
      siRNA raised to 120 nmol/L, the inhibitory rate reached to the peak. The
      inhibitory rate of siRNA-1 on proliferation of HEL cells, relative expression
      level of evi1 mRNA and cell viability at 48 hours after transfection were 72.22
      +/- 2.80%, 27.31 +/- 1.11% and 26.05 +/- 2.49%, which had significant difference
      from other groups (p < 0.001). The siRNA resulted in arrest of cell cycle at
      G(0)/G(1) phase, the cell amount at S phase obviously decreased, the apoptotic
      rate of HEL cells obviously increased (p < 0.01). It is concluded that the siRNA
      specific for evi1 gene can suppress the proliferation of HEL cells, reduce the
      expression of evi1 mRNA, decrease the cell viability, arrest the cell cycle at
      G(0)/G(1) phase, suppress cell mitosis, and promote cell apoptosis.

PMID- 21176351
TI  - [Effect of bortezomib on MAPK signaling pathway of K562/DNR cells].
AB  - The study was aimed to investigate the effects of bortezomib (BTZ) on the
      expression of ERK, JNK and P38 in daunorubicin (DNR)-resistant K562 cells
      (K562/DNR) and to clarify the molecular mechanism of BTZ in reversing the drug
      resistance in leukemic cells. The K562/DNR cells and the cellular toxicity of BTZ
      was determined by MTT, then 4 ug/L of BTZ was chosen to do the experiment. The
      expression of ERK, JNK, p38 and P-gp of K562/DNR cells treated with DNR only or
      DNR combined with BTZ for 12, 24 and 36 hours was detected by Western blot. The
      apoptosis rate in each group was assayed by flow cytometry. The results showed
      that as compared with DNR group, the expression of P-ERK, P-P38 and P-gp was
      significantly suppressed (p < 0.05) and the expression of P-JNK was significantly
      enhanced (p < 0.05) in the cells treated with DNR combined with BTZ. There was no
      change in the expression of total ERK, P38 and JNK. The effect increased with the
      prolonging of time. Meanwhile, the apoptosis rate in cells treated with DNR
      combined with BTZ increased compared with DNR only. It is concluded that the BTZ
      can reverse the drug resistance in K562/DNR cells by MAPK signaling pathway and
      increase the apoptosis of leukemic cells. The effect shows the characteristics of
      time-dependent manner.

PMID- 21176352
TI  - [Effect of rapamycin on proliferation of acute myeloid leukemia cell lines HL-60
      and HL-60/VCR].
AB  - In order to investigate the effect of rapamycin on the proliferation of human
      acute myeloid leukemia (AML) cells, the sensitive cells HL-60 and multidrug
      resistant HL-60/VCR cells were chosen as research objects. The proliferation of
      cells was detected by growth curve method. The flow cytometer was used to analyze
      cell cycle. The expression of P-glycoprotein (Pgp) was determined by Western
      blot. The results demonstrated that there was a significant difference of cell
      growth inhibition rate between control group and rapamycin group (p < 0.05). The
      cell growth inhibition rate was dose- and time- dependent (p < 0.05). Flow
      cytometry detection showed that the cell percentage of G(1) phase in rapamycin
      group was higher than that in group without rapamycin, and that of S phase was
      lower. The cell growth inhibition rate in 50 nmol/L and 100 nmol/L rapamycin plus
      daunorubicin (DNR) group was more than that in DNR alone group (p < 0.05),
      especially when DNR was added at 24 hours interval after RAP. The expression of
      Pgp of HL-60/VCR cells was inhibited by rapamycin. It is concluded that the
      rapamycin can inhibit the proliferation of sensitive HL-60 and multidrug
      resistant HL-60/VCR cells. It can also increase sensitivity of HL-60 and HL
      60/VCR cells to DNR, which provides new strategy for the therapy of refractory
      AML.

PMID- 21176353
TI  - [Inhibitory effect of tanshinones on proliferation of K562 cell line and its
      structure-activity relationship].
AB  - The study was purposed to investigate the growth inhibitory effect of tanshinones
      on K562 cell line and the relationship between their structures and cytotoxicity.
      The modified MTT assay was adopted to measure the inhibitory effect of
      tanshinones at different concentrations and chemical structures on K562 cells,
      and the changes of cell morphology were observed by inverted phase contrast
      microscopy. The results indicated that the tanshinones could inhibit the
      proliferation of K562 cells effectively, and their cytotoxicities on K562 cells
      showed concentration- and time-dependent manners. The IC(50) of dihydrotanshinone
      I, tanshinone I, tanshinone IIA and cryptotanshinone at 24 hours were 0.91, 4.04,
      5.95, 13.85 ug/ml at 48 hours were 0.37, 1.35, 1.71, 6.71 ug/ml; at 72 hours were
      0.33, 0.46, 0.82, 6.02 ug/ml, respectively. It is concluded that all of the four
      tanshinones have proliferation inhibitory effect on K562 cell line, among them
      the dihydrotanshinone I is the most active one, followed by tanshinone I,
      tanshinone IIA and cryptotanshinone subsequently, indicating that the chemical
      structure of aromatic ring A of tanshinones can enhance their cytotoxicity and
      the structure of furan ring C may influence the cytotoxicity, but their mechanism
      is still remained to be further investigated.

PMID- 21176354
TI  - [Expression change of IL-3 receptor system in all-trans retinoic acid induced
      differentiation of NB4 cells].
AB  - Interleukin-3 receptor (IL-3R) is a heterodimeric membrane receptor. The alpha
      subunit is essential for ligand binding and confers ligand specificity to the
      receptor. The common beta chain (betac) subunit, which is shared by the
      granulocyte macrophage-colony stimulating factor (GM-CSF), IL-3 and IL-5
      receptors, is required for high-affinity ligand binding and signal transduction,
      mediating growth and survival of hematopoietic progenitor cells and the
      production and activation of mature hematopoietic cells. In order to investigate
      the role of IL-3 receptor system (IL-3Ralpha, GM-CSFRalpha and hbetac) in myeloid
      differentiation, the expression level of IL-3 receptor system gene in all-trans
      retinoic acid (ATRA)-induced NB4 cell differentiation was detected by
      quantitative real time RT-PCR. At the same time, DNA sequence change was analyzed
      by cDNA sequencing. The results showed that the expression level of IL-3Ralpha
      mRNA was obviously down-regulated in NB4 cells treated with ATRA for 24 hours,
      but during differentiation of ATRA induced NB4 cells, the expression level of IL
      3Ralpha mRNA was gradually restored, while the expression levels of GM-CSFRalpha
      mRNA and hbetac mRNA were gradually up-regulated. The sequence of IL-3Ralpha and
      GM-CSFRalpha gene did not change before and after NB4 cells differentiation, but
      the sequence of hbetac gene changed when NB4 cells were treated with ATRA, the
      expression of hbetac mRNA sequence before NB4 cell differentiation taken
      truncated mutation as dominant, as regards expression of hbetac mRNA sequence
      after NB4 cell differentiation, the truncated mutation of hbetac mRNA had
      restored to wild type. It is concluded that the IL-3 receptor abnormality exists
      in NB4 cells, over expression of IL-3Ralpha and truncated mutation of hbetac may
      be involved in proliferation and differentiation block in NB4 cells.

PMID- 21176355
TI  - [Effects of Chinese medicine compound FFJZ on proliferation and apoptosis of
      leukemia cell line K562].
AB  - This study was purposed to explore the biological effects suppressing growth and
      inducing apoptosis of Chinese medicine compound FFJZ on leukemia cell line K562
      and its possible mechanisms of FFJZ. The growth status of K562 cells cultured in
      vitro was determined by trypan blue exclusion test; the suppressive effect of
      FFJZ on K562 cells was assayed by MTT method; the inducing apoptosis of FFJZ on
      K562 cells was detected by flow cytometry. The results showed that after K562
      cells were treated with FFJZ in certain concentration range, the inhibited rate
      of FFJZ on K562 cell growth was remarkably increased along with enhancement of
      FFJZ, the IC(50) value of FFJZ on K562 cells was 5.6 mg/ml after treatment for 48
      hours. At 4 mg/ml of FFJZ the early apoptosis predominated in K562 cells, at 8
      mg/ml of FFJZ the late apoptosis ratio significantly increased. As compared with
      control group without FFJZ, there was significant difference (p < 0.01). It is
      concluded that the FFJZ in range of certain concentration can suppress growth and
      proliferation of K562 cells and induce their apoptosis in concentration-dependent
      manner, the mechanism of which may be associated to inducing apoptosis of K562
      cells.

PMID- 21176356
TI  - [Mechanism of As(2)O(3) on hdpr1 gene demethylation in Jurkat cell line].
AB  - This study was purposed to investigate the effect of As(2)O(3) on the
      demethylation of anti-oncogene-hdpr1 gene of acute lymphoblastic leukemia cell
      line Jurkat in vitro and its mechanism. The inhibitory effect of As(2)O(3) on the
      proliferation of Jurkat cells was assayed by CCK-8; the change of Jurkat cell
      cycle was detected by flow cytometry before and after using As(2)O(3); the effect
      of As(2)O(3) on the methylation model of hdpr1 gene was analyzed by methylation
      specific PCR, and the effect of As(2)O(3) on the expression of hdpr1 mRNA was
      analyzed by semiquantitative RT-PCR. The results showed that the proliferation
      rate of Jurkat cells was decreased significantly after being treated with
      As(2)O(3), and in dose-and time-dependent manner; As(2)O(3) blocked Jurkat cell
      cycle in G(0)/G(1) phase in dose-dependent manner. As(2)O(3) could reverse
      hypermethylation of hdpr1 gene and induce its mRNA reexpression, and down
      regulate the dnmt1, dnmt3a, dnmt3b mRNA expression level also in dose-dependent
      manner. It is concluded that the As(2)O(3) suppresses the proliferation of Jurkat
      cells and blocks cell cycle is G(0)/G(1), its possible mechanism may be down
      regulating mRNA expression level of dnmt1, dnmt3a and dnmt3b, induce
      demethylation of hdpr1 gene from abnormal hypermethylation status and activates
      its reexpression.

PMID- 21176357
TI  - [Relationship between coagulation function and international prognostic index in
      lymphoma patients].
AB  - The study was aimed to investigate the clinical significance of coagulation
      function changes in lymphoma patients and to analyze the relationship between
      their changes and international prognostic index (IPI). The prothrombin time
      (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and
      fibrinogen (FIB) were detected by magnetic bead method in 75 lymphoma patients
      and 20 healthy persons. The dehydrogenase (LDH) level was detected by rate method
      in all lymphoma patients and healthy persons. The results showed that (1) the
      APTT and FIB more obviously increased in lymphoma patients which displayed as
      hyperfibrinogenemia, as compared with control group (p < 0.05, p < 0.01); no
      obvious changes of coagulation indexes presented in patients with different ages
      and extranodal lesions (p > 0.05, p < 0.01). (2) APTT and FIB levels in stage III
      and IV patients were much higher than those in the stage II (p < 0.05 and <
      0.01), and FIB level in stage IV group was significantly higher than those in the
      stage III (p < 0.05). FIB level in symptomatic group was significantly higher
      than that in asymptomatic group (p < 0.01). (3) APTT and FIB in increased LDH
      group were obviously higher than those in control group (p < 0.05, p < 0.01).
      Furthermore, FIB in increased LDH group was higher than that in normal LDH group
      (p < 0.05). FIB in performance status (PS) 2 - 4 groups increased significantly
      as compared with those in PS 0-1 group (p < 0.01). (4)FIB levels in the low
      middle-risk, high-middle-risk and high-risk groups were significantly higher than
      those in control group (p < 0.01), while FIB levels in high-middle-risk and high
      risk groups were higher than those in low-risk group (p < 0.05). (5) the number
      of FIB increased patients in symptomatic group, increased LDH group, PS 2 - 4
      group and Ann Arbor stage III-IV group were much higher than those in
      counterparts (p < 0.05 or 0.01).There were positive correlations between FIB and
      LDH level, PS grades, Ann Arbor stages as well as risk grades respectively (p <
      0.05 or 0.01). It is concluded that lymphoma patients usually accompany with
      hyperfibrinogenemia which may be influenced by Ann Arbor stage, systemic symptom,
      LDH level and PS grade. FIB is supposed to be an effective indication of
      prognosis in lymphoma patients.

PMID- 21176358
TI  - [Clinical features of 16 cases of lymphoplasmacytic lymphoma/Waldenstrom
      macroglobulinemia].
AB  - In order to investigate the clinical manifestations, diagnosis, therapy and
      prognosis of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM),
      16 patients with LPL/WM were analyzed retrospectively. The results showed that
      the average age of 16 patients with LPL/WM was 65.1 years old, the most common
      syndromes were anemia and hyperviscosity syndrome, bone marrows were composed of
      small lymphocyte, admixed with variable numbers of plasma cells and plasmacytoid
      lymphocytes. And lymph node biopsy revealed that most cells expressed B-cell
      associated antigen. Among the 16 cases, complete remission was 25%, overall
      response rate (ORR) was 81.3%, overall survival time was 6 to 108 months. 3
      patients died and survival rate was 81.3 %. It is concluded that the clinical
      course of LPL/WM is typically indolent. These patients can acquire remission in
      clinic, but can not be cured, some of them can transform into patients with more
      malignant lymphoma.

PMID- 21176359
TI  - [Clinical and biological features of 8 patients with Richter's syndrome].
AB  - In order to evaluate the clinical, biological features and prognostic factors of
      Richter's syndrome (RS), 8 RS patients were analyzed retrospectively. The
      serological test, multiplex parameter flow cytometry, conventional cytogenetic
      analysis, FISH technique and PCR combined with sequence detection were used to
      detect the LDH, beta(2)-MG, TK1, SF, CA125, ZAP-70, chromosome karyotype, ATM and
      p53 gene deletion, as well as +12 abnormality and IgVH mutation. The results
      indicated that 7 out of 8 patients transformed to diffuse large B cell lymphoma
      (DLBCL) and 1 patient transformed to Hodgkin lymphoma (HL). Among 8 patients, LDH
      level in 7 patients, beta(2)-MG level in 4 patients, SF level in 7 patients, CA
      125 level in 4 patients and TK1 level in 1 patient exceeded the normal range.
      Meanwhile, ZAP-70 and CD38 were expressed positively in 4 and 7 out of 8 patients
      respectively. Unmutated IgVH was found in 5 patients, and 4 patients had the
      complex chromosome abnormalities. +12 and p53 deletion was found in 1 patient. 8
      patients were divided into two groups (Binet A + B and Binet C), the mean time
      from diagnosis to progression was 98.5 months in Binet A + B group, compared with
      38.3 months in Binet C group, there was significant difference between two groups
      (p = 0.021). Mean overall survival was 123.8 months and 49.8 months in two
      groups, respectively (p = 0.049). The mean survival after transformation was 34.5
      months in Binet A + B group and 10.3 months in Binet C group. In conclusion, the
      level of LDH, beta(2)-MG and SF are higher in RS patients in Binet C group, and
      so are the incidence of high expressed ZAP-70 and CD 38, unmutated IgVH. The
      clinical stage may be the risk and prognostic factors for RS transformation.

PMID- 21176360
TI  - [Comparative study of genetic aberrations in human multiple myeloma cell lines
      and newly diagnosed MM by fluorescence in situ hybridization].
AB  - Multiple myeloma (MM) is a neoplasm of a terminally differentiated B-cell. Human
      myeloma cell lines were shown to be suitable model systems for use in various
      fields of the biological sciences. This study was aimed to investigate the
      genetic aberrations in human multiple myeloma cell lines. Interphase fluorescence
      in situ hybridization (FISH) with probes for the regions containing 13q14 (RB-1),
      13q14.3 (D13S19), 14q32 (IGHC/IGHV) , 1q12 (CEP1), 17p13 (TP53) were was used to
      detect 7 HMCL and 85 cases of newly diagnosed MM. FISH with LSI IGH/CCND1 , LSI
      IGH/FGFR3 and LSI IGH/MAF probes were used to detect t(11;14) (q13;q32) , t(4;14)
      (p16;q32) and t(14;16) (q32;q23) in HMCL and MM with 14q32 rearrangement. The
      results showed that molecular cytogenetic aberrations were found in all 7 HMCL,
      six (85.7%) HMCL simultaneously had 13q14, 13q14.3 deletion. Chromosome 1q21
      abnormality was found in six (33.3%) HMCL with at least 3 copies amplifications.
      Illegitimate 14q32 rearrangement was found in five (71.4%) HMCL, including one
      with t(11;14), two with t(4;14) and three with t(14;16). 17p13 deletion was
      detected in 5 HMCL. Chromosomal changes were observed in 85.9% of the 85 cases of
      newly diagnosed MM. The del(13), 1q12 amplification, del(17p), 14q32
      rearrangement, t(11;14), t(4;14), t(14;16) were present in 44.7%, 52.9%, 20%,
      62.4%, 27.1%, 24.7% and 3.5% of the patients respectively. There was no
      significant difference in the prevalence of genetic abnormalities of del(13q),
      14q32 rearrangement, 1q12 amplification, t(11;14), t(4;14) except del(17p) and
      t(14;16). It is concluded that HMCL representative of the most aggressive phase
      of plasma cell neoplasms accumulated a large amount of genetic aberrations. Loss
      of p53 are strikingly common in HMCL suggesting that the impairment of the P53
      tumor suppressor pathway is an important contributor to extramedullary tumor
      expansion.

PMID- 21176361
TI  - [Therapeutic efficacy of bortezomib-based chemotherapy on 40 patients with
      multiple myeloma].
AB  - This study was aimed to investigate the therapeutic efficacy and adverse events
      of bortezomib-based chemotherapy for 40 patients with multiple myeloma. 16 newly
      diagnosed patients and 11 patients with refractory/relapse myeloma were treated
      with bortezomib, dexamethasone and thalidomide; 7 newly diagnosed patients and 4
      patients with refractory/relapse myeloma were treated with bortezomib and
      dexamethasone; 2 newly diagnosed patients were treated with bortezomib, melphalan
      and thalidomide. Cycles were repeated every 28 or 35 days, all the patients were
      treated for 2 to 8 cycles. The therapeutic efficacy and adverse events were
      evaluated according to International Myeloma Working Group Uniform Response
      Criteria. The results indicated that the median follow-up duration was 13 months,
      the total response rate was 72.5%, among which 16 patients achieved complete
      response (CR), 13 achieved partial response (PR). The main side effects included
      gastrointestinal symptoms, peripheral neuropathy, thrombocytopenia, respiratory
      infection, herpes zoster and urinary retention and so on. The adverse events were
      ameliorated by treatment and decrease of the bortezomib dose. It is concluded
      that bortezomib-based chemotherapy is effective in the treatment of either newly
      diagnosed or refractory/relapse MM patients and the adverse events are tolerable
      and manageable for patients.

PMID- 21176362
TI  - [Effect of sodium valproate on human myelodysplastic syndrome cell line SKM-1 and
      its mechanism].
AB  - This study was aimed to investigate the effect of sodium valproate(VPA) on human
      myelodysplastic syndrome cell line SKM-1 and its mechanism. The cell
      proliferation was determined by MTT assay, cell apoptosis was analyzed by flow
      cytometry. The expressions of c-flipl, c-flips and dlk1 mRNA were detected by RT
      PCR. The results showed that VPA could inhibited the growth of SKM-1 cells in
      dose- and time-dependent manners. The flow cytometric analysis indicated that VPA
      could induce cell apoptosis, apoptosis rate increased in dose-dependent manner.
      The expressions of c-flipl, c-flips and dlk1 mRNA in SKM-1 cell treated with VPA
      decreased using of VPA. It is concluded that VPA can induce apoptosis and
      inhibited proliferation of SKM-1 cells. In this process, the decreasing of c
      flipl, c-flips and dlk1 mRNA expression may play important roles.

PMID- 21176363
TI  - [Effect of rhG-CSF on blood coagulation in beagles irradiated by 2.3 Gy neutron].
AB  - The aim of this study was to investigate the effect of recombinant human
      granulocyte stimulating factor (rhG-CSF) on blood coagulation of beagles
      irradiated by 2.3 Gy neutron so as to provide new therapy for blood coagulation
      disorder after neutron irradiation. 10 beagles were exposed to 2.3 Gy neutron,
      and then randomly assigned into supportive care group and rhG-CSF-treated group.
      The rhG-CSF-treated cohorts were injected subcutaneously with rhG-CSF (10
      ug/kg.d) beginning at the day of exposure for 21 consecutive days. Peripheral
      blood platelet counts were examined once every two days. In vitro platelet
      aggregation test, thromboelastography and blood clotting tetrachoric tests were
      also performed. The results indicated that the blood clotting system of
      irradiated dogs was in hypercoagulable state in the early days after 2.3 Gy
      neutron irradiation, and became hypocoagulable at crisis later and were mainly on
      intrinsic coagulation pathway. Blood fibrinogen increased markedly during the
      course of disease, while platelet counts and aggregation function were decreased
      remarkably. rhG-CSF administered daily could correct hypercoagulable state
      induced by 2.3 Gy neutron irradiation at the early time post exposure, shortened
      the thromboplastin generation time and clotting formation, down-regulated the
      abnormal high fibrinogen in blood, and improved platelet aggregation function. It
      is concluded that rhG-CSF can improve coagulation disorders of irradiated dogs.

PMID- 21176364
TI  - [Clinical analysis of 10 cases of secondary hemophagocytic lymphohistiocytosis
      treated with HLH-2004 chemotherapy].
AB  - This study was aimed to investigate the therapeutic efficacy of HLH-2004
      chemotherapy in patients with secondary hemophagocytic lymphohistiocytosis
      (sHLH). 10 cases of sHLH treated with HLH-2004 regimen at our department were
      analyzed retrospectively. The results showed that 7 patients had clinical
      response to HLH-2004 regimen, while other 3 patients had no clinical response. 5
      cases did not complete initial therapy of 8 weeks. Out of 5 cases, 4 died in the
      process of chemotherapy, 1 patient abandoned for serious side effects but finally
      acquired remission following 4 cycles of CHOP regimen. 5 cases underwent the
      whole courses of initial therapy. Out of 5 cases, 3 patients acquired remission,
      and other 2 were not well controlled. Out of the 3 patients who had achieved
      remission, one died of relapse, and other 2 patients kept remission. Out of the 2
      patients who were not well controlled, one patient died, but another patient
      acquired remission after being discharged. It is concluded that patients with
      infection-associated hemophagocytic syndrome (IAHS) have high rates of remission
      after receiving HLH-2004 regimen combining with effective antibiotics. However,
      patients with HLH secondary to EBV (EBV-HLH) or lymphoma (LAHS) have low rates of
      remission or are easy to get relapse after remission.

PMID- 21176365
TI  - [Quantitative chimerism analysis of regulatory T cell subsets based on
      immunomagnetic sorting].
AB  - The aim of study was to explore the feasibility of quantitative chimerism
      analysis of regulatory T (Treg) cells using immune sorting coupling short tandem
      repeat (STR) method. 14 sets of artificial chimera samples were prepared by mixed
      lymphocytes according to different proportion. The CD4(+)CD25(+) Treg cells were
      harvested by negative and positive selection of immunomagnetic beads, then the
      STR polymorphisms of 16 loci in sorted Treg cells was analyzed. The results
      showed that the DNA amount extracted from sorted Treg cells was fit for STR
      detection. All STR alleles specific for recipient or donor could be detected and
      the quantitative results were consistent with theoretic values in over 10%
      recipient chimeras. But only partial recipient alleles could be detected and the
      quantitative results were different from theoretic values in less then 1%
      recipient chimeras. It is concluded that a quantitative chimerism analysis of
      Treg cell based on immune sorting is established. The sensitivity and accuracy
      for chimera detection are 1% to 10%, and this method can be used to monitoring
      hematopoietic chimerism following allogeneic hematopoietic stem cell
      transplantation.

PMID- 21176366
TI  - [Analysis of maternal and neonatal factors associated with hematopoietic
      reconstruction potential in umbilical cord blood units].
AB  - Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cells
      for transplantation with success being associated with the total nucleated cell
      (TNC) count, CD34(+) cells and colony-forming unit-granulocyte-macrophage (CFU
      GM) content infused. This study was purposed to clarify the impact of maternal
      and neonatal factors on hematopoietic potential of UCB product. UCB samples were
      screened, processed, tested and cryopreserved according to the Standard Operation
      Procedure (SOP) of Guangzhou cord blood bank (GZCBB). Relationship of
      hematopoietic cell parameters with maternal and neonatal characteristics for 4615
      UCB units was analyzed retrospectively. The results showed that both collected
      volume (Mean +/- SD: 95.23 +/- 22.42 ml; Median: 91.85 ml) and initial TNC [Mean
      +/- SD: (1.34 +/- 0.49) * 10(9); Median: 1.25 * 10(9)] correlated well with
      postprocessed TNC [Mean +/- SD: (1.21 +/- 0.42) * 10(9); Median: 1.14 * 10(9); p
      < 0.001], CD34(+)count [Mean +/- SD: (5.14 +/- 4.55) * 10(6); Median: 4.08 *
      10(6); p < 0.001] and CFU-GM content [Mean +/- SD: (9.72 +/- 8.66) * 10(5);
      Median: 7.53 * 10(5); p < 0.001]. As for donor factors, only infant birth weight
      correlated strongly with volume collected and all hematopoietic cell parameters
      (p < 0.001). UCB samples from bigger babies had higher collected volume, TNC,
      CD34(+) count and CFU-GM content (p < 0.001). Mother's age had no correlation
      with all the above parameters. Gestational age correlated positively with
      initial/postprocessed TNC (p < 0.001) and negatively with CD34(+) count (p =
      0.04), but no relation with collected volume and CFU-GM content. Cesarean section
      produced superior volume (Mean +/- SD: 97.05 +/- 22.23 ml vs 92.53 +/- 22.43 ml;
      Median: 94.08 ml vs 88.82 ml; p < 0.001), but inferior cell count than vaginal
      delivery (p < 0.001). Male infants had more initial volume and CD34(+) count
      (Mean +/- SD: 96.41 +/- 22.31 ml vs 93.95 +/- 22.47 ml; Median: 93.27 ml vs 90.14
      ml; p < 0.001); [Mean +/- SD: (5.28 +/- 5.04) * 10(6) vs (5.00 +/- 3.94) * 10(6);
      Median: 4.18 * 10(6) vs 3.94 * 10(6); p < = 0.042], but lower initial and
      postprocessed TNC than female ones [Mean +/- SD: (1.31 +/- 0.50) * 10(9) vs (1.37
      +/- 0.47) * 10(9); Median: 1.22 * 10(9) vs 1.28 * 10(9); p < 0.001]; [Mean +/-
      SD: (1.18 +/- 0.42) * 10(9) vs (1.24 +/- 0.41) * 10(9); Median: 1.10 * 10(9) vs
      1.17 * 10(9); p < 0.001], while no significant difference of CFU-GM were found
      between male and female infants. It is concluded that these data may be helpful
      to optimize the UCB donor selection and improve cost efficiency of UCB bank
      resource. The heavier infants after vaginal delivery should be selected and large
      volume units with higher TNC should be chosen at first.

PMID- 21176367
TI  - [NK-T cell activator (alpha-GalCer) accelerates immune and hematological
      reconstitution after murine allo-bone marrow transplantation].
AB  - Immune reconstitution is crucially relevant for patients receiving hematopoietic
      stem cell transplantation (HSCT). This study was purposed to investigate the
      ability of alpha-GalCer (alpha-galactosylceramide), a well-known activator of
      natural killer T cells (NK-T), to enhance immune and hematological
      reconstitution. Lethally irradiated BALB/c mice were transplanted with allogeneic
      C57BL/6 bone marrow cells and splenocytes. alpha-GalCer was administered
      immediately after HSCT. After transplantation, the weight, activity, hairs,
      diarrhea and survival time of mice were observed daily; the blood routine test
      was performed once weekly; the donor chimeras, amount of mononuclear cells in
      spleen (MNC) and relative levels of CD3(+), CD4(+), CD8(+), B220(+), CD11c(+),
      CD40(+), CD86(+) and CD80(+) cells were detected by FACS on day 2, 7, 14, 27, 70
      after transplantation. The results indicated that the MNC counts and relative
      levels of CD3(+) and CD4(+) in group treated with alpha-GalCer on day 2 after
      transplantation were higher than those in control group; at the same time, the
      detected donor chimeras were complete recipient type chimeras, then gradually
      transformed into donor type, on day 7 - 14 donor chimeras in alpha-GalCer group
      were enhanced significantly as compared with control group, on day 27 the
      chimeras in two groups were complete donor type chimeras thereafter to day 70,
      the MNC count and relative levels of CD3(+), CD4(+), CD8(+), B220(+), CD40(+),
      CD86(+) cells in alpha-GalCer group were obviously higher than those in control
      group, at the same time, the hematopoietic reconstitution in alpha-GalCer group
      was accelerated as compared with control group. It is concluded that the alpha
      GalCer administration after allogeneic bone marrow transplantations accelerates
      immune and hematological reconstitution.

PMID- 21176368
TI  - [Effects of rhG-CSF mobilization on Th17 cells in donors' peripheral blood and
      bone marrow grafts].
AB  - The study was aimed to explore the effects of recombination human granulocyte
      colony-stimulating factor (rhG-CSF) on Th17 cells in donors' peripheral blood
      (GPB) and bone marrow grafts (GBM). 25 healthy donors were injected
      subcutaneously with rhG-CSF 5 ug/(kg.d) for 5 consecutive days. GBM and GPB were
      harvested after injection on day 4 and 5 respectively. Some of these donors'
      steady-state bone marrow (SSBM) and steady-state peripheral blood (SSPB) were
      harvested before rhG-CSF injection. The changes of IL-17 secreted by T cells in
      donor BM and PB before and after mobilization were detected by flow cytometry.
      The results showed that the ability to secrete IL-17 from CD4(+) T cells and
      CD8(+) T cells in GBM was significantly lower than those in SSBM (GBM vs SSBM
      Th17/CD4(+) T, 0.74% +/- 0.27% vs 1.78% +/- 1.19%, p < 0.05; Tc17/CD8(+)T, 0.19%
      +/- 0.16% vs 0.36% +/- 0.37%, p < 0.05), changes in peripheral blood and bone
      marrow were same (GPB vs SSPB Th17/CD4(+) T, 1.82% +/- 0.91% vs 3.26% +/- 1.89%,
      p < 0.01; Tc17/CD8(+) T, 0.21% +/- 0.17% vs 0.44% +/- 0.28%, p < 0.01). The
      ratios of Th17/CD4(+) T and Tc17/CD8(+) T in GPB were higher than in GBM (p <
      0.05, p < 0.01). It is concluded that rhG-CSF in vivo can inhibit the generation
      of Th17 cells both in bone marrow and peripheral blood grafts, and it may be
      partial reason for GPB/GBM mixed transplantation without increasing the GVHD
      incidence.

PMID- 21176369
TI  - More mesenchymal stem cells enriched from bone marrow aspirates by culturing bone
      marrow particles and mononuclear cells separately.
AB  - Bone marrow (BM) is the major source of mesenchymal stem cells (MSC). In most
      experiments, MSC were classically cultured from mononuclear cells (MNC) isolated
      by density gradient centrifugation method. However, several studies have
      demonstrated that this method was less efficient for MSC recovery. This study was
      aimed to investigate whether BM particles were the cause resulting in less
      efficiency of this method and how to isolate them. A total of 20 patients were
      enrolled in this study. MNC were cultured by standard adherence and BM particles
      were cultivated by primary explant culture. For BM from patients 1-10, MNC were
      first isolated and BM particles were then filtered out. The morphology and the
      fibroblastic colony number were compared between cultures of MNC and BM
      particles. For BM from patients 11-20, MNC isolation and BM particle filtration
      were processed in opposite order, then the immunophenotype and function between
      adherent cells expanded from MNC and BM particles were compared. In addition, for
      patients 11-20, the left BM aspirates were cultured too after BM particles and
      MNC were isolated separately. The results showed that adherent cells from BM
      particles were MSC. After BM particles were filtered out and cultured separately,
      MSC could be recovered completely from MNC isolated by density gradient
      centrifugation and no MSC were left in the residual BM aspirates. BM particles,
      which have been mostly discarded by the method of density gradient
      centrifugation, are another important source of MSC and they can be cultivated
      reliably by primary explant culture. It is concluded that more MSC are recovered
      from a single BM sample by culturing BM particles and MNC separately.

PMID- 21176370
TI  - [Change of cytokine expressions on bone marrow mesenchymal stem cells in patients
      with bone marrow failure syndromes and its significance].
AB  - This study was aimed to investigate the expressions of multiple cytokines on bone
      marrow mesenchymal stem cells (MSC) in patients with aplastic anemia (AA) and
      myelodysplastic syndrome (MDS), and its significance. The semi-quantitative
      reverse transcriptase-PCR (RT-PCR) was used to detect the expressions of IL
      1beta, SCF, G-CSF at mRNA level in bone marrow MSC of patients with AA and MDS.
      The real time quantitative polymerase chain reaction (RQ-PCR) technique was used
      to detect the mRNA expression of TPO in bone marrow MSC of AA and MDS patients.
      The results indicated that the expression of SCF in AA group was much lower than
      that in the normal control group (p < 0.05), and the expression of TPO in AA
      group was higher than that in the normal control group (p < 0.05), while the
      expression of IL-1beta of AA had no significant difference when compared with the
      normal control group (p > 0.05). Compared with normal control group, the
      expressions of SCF of MDS patients was lower (p < 0.05), but the expressions of
      IL-1beta and TPO did not show significant difference (p > 0.05). The expressions
      of IL-1beta, SCF and TPO were no significant difference between AA and MDS groups
      (p > 0.05). Neither the AA patients, MDS patients nor the normal control group
      had the expression of G-CSF. It is concluded that the expression of SCF and TPO
      in bone marrow MSC of AA patients are obviously abnormal, the expression of SCF
      is also abnormal in bone marrow MSC of MDS patients.

PMID- 21176371
TI  - [Regulatory effect of thymosin alpha1 on expression of tlr9/ido mRNA in bone
      marrow mesenchymal stem cells from children with aplastic anemia].
AB  - The purpose of this study was to explore the regulatory effect of thymosin alpha1
      (Talpha1) on expression of TOLL-like receptor 9 (TLR9)/indoleamine2, 3
      dioxygenase (ido) mRNA in bone marrow mesenchymal stem cells (MSC) from children
      with aplastic anemia (AA). Culture system of bone marrow MSC from AA children and
      normal children in vitro was established, and the effects of Talpha1 on
      expressions of tlr9 mRNA and ido mRNA of MSC from AA children and normal children
      were determined by RT-PCR. The results showed that the bone marrow MSC from
      normal children did not express tlr9 and ido mRNA. Bone marrow MSC from children
      with AA obviously expressed tlr9 mRNA , but did not express ido mRNA; AA
      children's MSC treated with Talpha1 for 18 hours markedly down-regulated tlr9
      mRNA expression, but up-regulated ido mRNA expression in the concentration- and
      time-dependent ways. It is concluded that Talpha1 can up-regulate the expression
      of ido mRNA in bone marrow MSC from children with AA.

PMID- 21176372
TI  - [Effect of mesenchymal stem cells transfected with human vegf-165 gene carried by
      adenovirus on revascularization for hind limb ischemic necrosis in rat model].
AB  - The aim of study was to explore the effect of mesenchymal stem cells (MSC)
      transfected with recombinant adenovirus-mediated human vascular endothelium
      growth factor 165 (ad-vegf-165) on treating ischemic necrosis limbs. Adult SD
      rats were selected for study. Limb ischemic necrosis model was established by
      right femoral artery ligation in SD rats. 7 days after ligation, MSC, ad-h-vegf
      165-MSC and ad-LacZ-MSC labelled by DAPI were injected into ischemic necrosis
      limb in rats respectively. One week after injection, the expression of VEGF in
      ischemic necrosis limbs was detected by Western blot. And at 1, 2 or 4 weeks
      after injection, the expressions of FVIII and myosin on MSC were evaluated by
      immunohistochemistry. The results indicated that the MSC labelled by DAPI could
      be found in the transplantation site of ischemic necrosis limbs under fluorescent
      microscope. And the number of MSC in MSC-vegf group was more than that in MSC and
      MSC-LacZ groups. The VEGF expression in MSC-vegf group was higher than that in
      MSC and MSC-LacZ groups. More importantly, the number of endothelial cells
      demonstrated characteristic FVIII positive MSC in MSC-vegf group was more than
      that in MSC and MSC-LacZ group after injections of 1, 2 and 4 weeks. However, the
      number of myosin positive MSC among MSC-vegf, MSC and MSC-LacZ groups showed no
      significant difference. It is concluded that MSC transfected with Ad-vegf
      promotes angiogenesis to repair ischemic necrosis limbs through the increased
      expression of VEGF.

PMID- 21176373
TI  - [Effect of endomorphin-1 on hematopoietic regulatory molecules from normal human
      bone marrow stromal cells].
AB  - The aim of study was to investigate the regulatory effect of endomorphin-1 (EM-1)
      on ICAM-1 and VCAM-1 on normal human bone marrow stromal cell surface as well as
      IL-6 and TNF-alpha excreted by human normal bone marrow stromal cells. The
      expression of ICAM-1 and VCAM-1 was determined by flow cytometry, and the
      concentration of IL-6 and TNF-alpha was detected by ELISA. The results indicated
      that the expression of ICAM-1 and VCAM-1 was significantly different from the
      control group after being cultured with endomorphin-1 for 24 hours (p < 0.05),
      and different concentrations of endomorphin-1 had no effect on expressions of
      ICAM-1 and VCAM-1 both; there was no difference in secretion of IL-6 and TNF
      alpha between experimental and control groups (p > 0.05). It is concluded that
      endomorphin-1 regulates the ICAM-1 and VCAM-1 expression on human normal bone
      marrow stromal cell surface, but endomorphin-1 does not display any effect on IL
      6 and TNF-alpha secreted by human normal bone marrow stromal cells.

PMID- 21176374
TI  - [Injury of bone marrow endothelial niche by irradiation myeloablative
      conditioning in mouse allo-BMT].
AB  - The aim of study was to investigate the injury of bone marrow microenvironment
      after gamma ray irradiation conditioning in mouse allogeneic hematopoietic stem
      cell transplantation (allo-HSCT). The mononuclear cells collected from mice bone
      marrow for culture in vitro, were identified by flow cytometry with double
      staining when cultured for 5 - 7 days. Mice were separated randomly into 4
      groups, namely, the control group, irradiation group, endothelial progenitor cell
      (EPC) transplantation group and irradiation combined EPC transplantation group.
      Peripheral blood was collected to assay the circulating white blood cells. The
      histological, electron microscopic and immunofluorescence analyses of bone marrow
      were performed in the same time, furthermore the distribution of labeled EPC was
      determined. The results showed that EPC were identified as CD45(low/
      )CD133(+)CD31(+), double positive of Dil-Ac-LDL and FITC-UEA-1. The bone marrow
      microenvironment injury of recipient mice was shown in the irradiation group in
      which the number of WBC began to decrease after conditioning, and the mice were
      all died at 8 days (p < 0.05). The intramedullary hemorrhage could be detected by
      light microscopy at 3 days after irradiation, when the destruction of connection
      between endothelial cell and the basement membrane was observed by TEM. There
      were CFSE labeled cells in bone marrow in irradiation combined EPC
      transplantation group at 18 hours after transplanted cultured EPC in vitro, the
      number of CFSE(+) cells was 58-folds of EPC transplantation group (p < 0.05). It
      is concluded that the irradiation can cause the severe endothelium injury that
      drives extrinsic EPC homing to the injured bone marrow microenvironment.

PMID- 21176375
TI  - [Influence of excessive complement activation on pathological process of acute
      graft versus host disease in mice].
AB  - This study was aimed to explore the influence of excessive complement activation
      on the pathological process of acute graft-versus-host disease (aGVHD) in mice. A
      murine model with aGVHD was established by injecting cell mixture containing
      splenocytes and bone marrow cells at 2:1 ratio from donor C57BL/6(H-2K(b)) mice
      into recipient BALB/c (H-2K(d)) mice within 4-6 hours after 8 Gy (60)Co gamma-ray
      total body irradiation. The mice received syngeneic bone marrow transplantation
      were used as control group. After transplantation, the mice were monitored daily
      for body weight and mortality. At day 14, all mice were sacrificed and each liver
      was freshly dissociated for histological analysis. The hepatic mRNA abundance for
      complement components C3a and C5a as well as receptors for these two
      anaphylatoxin were tested by real-time quantitative PCR method. And the levels of
      C3a and C5a production in liver were detected by ELISA. The deposition of
      complement C3 in liver was determined by immunofluorescence staining using frozen
      section. The results indicated that as compared with syngeneic bone-marrow
      transplantation control group, experimental animals underwent aGVHD characterized
      by weight loss, depilation, diarrhea and lassitude. Interestingly, the hepatic
      mRNA expression for complement anaphylatoxin family member C3a and C5a as well as
      their receptors C3aR and C5aR1 in mice with aGVHD were significantly up-regulated
      in comparison with control group (p < 0.05). Consistently, the content of C3a and
      C5a in liver increased markedly in mice with aGVHD (p < 0.01). For animals
      ongoing aGVHD, complement component C3 depositions were observed in hepatic
      portal areas, around which massive inflammatory cell infiltration was also
      observed. It is concluded that in aGVHD animals, excessive complement activation
      occurs, and the activated complement components participate in pathological
      process of the aGVHD.

PMID- 21176376
TI  - [In vitro expansion of T cells stimulated by combination of IL-2, IL-7 and IL
      15].
AB  - The aim of this study was to compare cell proliferation and function of the T
      cells acquired under various culture conditions for establishing a simple, safe
      and efficient cell expansion protocol in vitro. The peripheral blood mononuclear
      cells (PBMNC) were isolated and stimulated with autologous dendritic cells (DC)
      and EBV-transformed B lymphoblastoid cell line (BLCL) weekly. The cell
      proliferation test, flow cytometry with PI and Annexin V double staining, Cr
      release test and ELISPOT test were used to detect the cell expansion level,
      frequency of IFN-gamma producing T cells, killing activity of antigen-specific T
      cells, cell apoptotic status and cell differentiation potential, respectively.
      The results indicated that use of IL-2 combined with IL-7 and IL-15 resulted in
      the highest cell expansion comparing to the use of IL-2 alone and the use of
      CD3/28 Microbeads. Also the cells obtained under cultivating with IL-2, IL-7 and
      IL-15 together showed high frequency of IFN-gamma producing cells, strong killing
      activity, high viability and high differentiation potential with large portion of
      CD3(+)CD8(+) population among the T cells. It is concluded that a protocol is
      established in which the use of IL-2 combined with IL-7 and IL-15 induces the
      biggest cell expansion, expanded cells show high viability, strong
      differentiation potential, high frequency of IFN-gamma producing cells and strong
      killing activity.

PMID- 21176378
TI  - [Construction of lentiviral vector carrying mouse RORgammat and expression of
      RORgammat in 293FT cells].
AB  - This study was aimed to construct a lentiviral vector carrying mouse RORgammat
      and glp gene, and to detect the expression of RORgammat in the 293FT cells. The
      RORgammat fragment was amplified by RT-PCR from mouse thymus and cloned into PCR
      2.1 vector. The RORgammat DNA fragment was prepared by digestion and inserted
      into MigR1 plasmid, then the RORgammat-IRES-GFP was directionally linked with
      lentiviral transfer plasmid pTK208 to generate a lentiviral vector pXZ9
      RORgammat. The recombinant lentivirus were produced by co-transfected three
      plasmids into 293FT packing cells using lipofectamine 2000. After transfection,
      the lentiviral supernatant was collected and concentrated via
      ultracentrifugation. The 293FT cells were infected by the concentrated
      lentivirus, GFP expression was examined under a fluorescent microscope and the
      expression of RORgammat protein was detected by Western blot. The results showed
      that the RORgammat fragment was amplified from cDNA of mouse thymus and
      recombinant lentiviral vector pXZ9-RORgammat was constructed successfully. High
      titer lentivirus were prepared after one round ultracentrifugation. RORgammat
      expression could be detected in 293FT cells after virus infection. It is
      concluded that the lentiviral vector pXZ9- RORgammat containing mouse RORgammat
      IRES-GFP is successfully constructed; RORgammat can express in 293FT cells via
      lentiviral vector transduction, which provides an optional tool for further
      research on the mechanism of RORgammat controlling Th17 cell differentiation.

PMID- 21176377
TI  - [Targeted regulation of mll-af4 fusion gene by miR-142-3p].
AB  - In order to analyze the possible epigenetic regulation mechanism of mll-af4 gene
      expression and find the possible microRNA regulating mll-af4 gene expression,
      targetscan software was used to analyze potential microRNA target sites in 3'-UTR
      of mll-af4. 3'-UTR fragment of mll-af4 was amplified by PCR. PCR products were
      cloned into EcoR I/Pst I-digested pGL3-M reporter vector, placing the 3'-UTR with
      potential microRNA binding site downstream of coding sequence of luciferase. The
      construct was cotransfected in 293T cells with control plasmid or plasmids
      expressing microRNAs regulating mll-af4 potentially. Western blot and RT-PCR were
      used to detect the expression level of mll-af4 protein and mRNA in RS4; 11 cells
      after transfection of miR-142-3p, respectively. The results showed that the pGL3
      AF4-3'UTR of luciferase reporter recombinant plasmid contain the 3'UTR sequence
      of mll-af4 gene with 1935 bp, 2104 bp and 1371 bp was constructed successfully
      and was confirmed by enzyme digestion and gene sequencing. The luciferase assay
      revealed that overexpression of miR-142 could reduce the luciferase activity from
      the reporter construct containing the mll-af4 3'-UTR significantly. Protein and
      mRNA expressions of mll-af4 were found to be downregulated by miR-142-3p. It is
      concluded that miR-142-3p regulates the expression of mll-af4 through target
      binding the mll-af4 gene 3'UTR site.

PMID- 21176379
TI  - [Amaxa Nucleofector(TM) nuclear transfection apparatus transfers L1210 cell
      line].
AB  - Mouse L1210 leukemia cell line is widely used as a model in the study of
      tumorigenesis, as well as the efficacy of chemotherapeutic drugs; however, like
      other suspension cell lines, the mouse L1210 cell line has lowest transfection
      efficiency, that many barriers exist to study about the structure, function, as
      well as metabolism in leukemia cells. This study was aimed to obtain higher
      transfection efficiency of L1210 cell line to facilitate scientific research. The
      transfection efficiencies of nucleofector and liposome in L1210 leukemia cells
      were detected by converted fluorescence microscopy and flow cytometry using EGFP
      (enhance green fluorescent protein); cell viability was observed by trypan blue
      exclusion test. The results showed that the transfection efficiency of
      nucleofector primarily through reporter gene pEGFP by Amaxa Nucleofector(TM)
      nuclear transfer apparatus was significantly higher than lipofectamine 2000
      transfection, furthermore, in the same cell density (2 * 10(6)/ml) and plasmid
      content (10 ug), the transfection efficiency of nuclear transfer apparatus
      default mode A-20 was higher than that of other modes (S-18, T-20). Its survival
      rate was up to 50.5% after 24 hours. Cell viability of liposome transfection
      reached to 88% after 24 hours, but the transfection efficiency was lower (< 1%).
      It is concluded that the nuclear transfer apparatus A-20 transfected L1210 can
      reach higher transfection efficiency up to 61.6%, which is significantly higher
      than that of lipofectamine transfection. The survival rate is up to 50.5% well
      meeting the needs of scientific research. Higher transfection efficiency is
      helpful for in-depth research about the morphology, functions and pathogenesis in
      leukemia model L1210, and provides more searching space for the treatment of
      leukemia diseases.

PMID- 21176380
TI  - [Construction and identification of ha1 recombinant lentiviral vector].
AB  - This study was aimed to construct a lentiviral vector of ha1 gene and obtain a
      stable packaging cell lines, which will be beneficial to guiding further study on
      the foundation of ha1 on the dissociation of graft versus host disease (GVHD) and
      graft versus leukemia (GVL) effect after allogenic hematopoietic stem cell
      transplantation (allo-HSCT). The targeting ha1 gene was obtained from plasmid T
      ha1 by digesting. Then the ha1 gene was subcloned into the lentiviral vector
      pRRLSIN, cPPT, PGK/GFP, WPRE to construct a lentiviral vector carrying ha1 gene
      named pLenti-ha1 plasmid. And the pLenti-ha1 plasmid was confirmed by PCR,
      digesting and sequencing. 293T cells were co-transfected with lentiviral vector
      pLenti-ha1 and packaging system. The titer of virus was tested by real-time PCR.
      The results indicated that the construction of ha1 recombinant lentiviral vector
      was confirmed to be exact by PCR assay, digesting and sequencing; the assayed
      titer of virus was 2.0 * 10(8) TU/ml. In conclusion, the lentiviral vector of ha1
      gene is constructed successfully.

PMID- 21176381
TI  - [In vitro expression activity of alpha-(1,2) fucosyltransferase with 35C > T and
      682A > G mutations].
AB  - In order to explore the effects of 35C > T and 682A > G mutations on the activity
      of alpha-(1,2) fucosyltransferase, the coding region of fut1 gene was amplified
      by polymerase chain reaction (PCR) from genomic DNA. PCR product was ligated into
      expression vector using TOPO TA cloning kit to obtain the recombinant plasmids.
      The recombinant plasmids were transfected into COS-7 cells by liposome method.
      After screening by using G418, H antigen expression on the COS-7 was tested by
      flow cytometry and fut1 mRNA was detected by real-time PCR. The results indicated
      that three kinds of recombinant plasmids pcDNA3.1/V5-His-wild (35C + 682A),
      pcDNA3.1/V5-His-35T and pcDNA3.1/V5-His-35T-682G were successfully constructed.
      After transfection, the H antigen expressed on membrane of COS-7 cells at the
      second day, with the maximum level of expression at the fourth day. When compared
      with pcDNA3.1/V5-His-wild transfected cells, the H antigen expression level of
      the 35T and 682G + 35T recombinant plasmids in the transfected cells was 52.7%
      and 13.3% on the fourth day, respectively. Although the level of fut1 mRNA
      decreased with prolonging of time, the mRNA expressed on the pcDNA3.1/V5-His-35T
      682G transfected cells reached to 14% of the wild plasmids on the first day. It
      is concluded that 682A > G mutation obviously reduces the activity of alpha-(1,2)
      fucosyltransferase, while 35C > T mutation leads to partial reduction of H
      antigen in vitro expression.

PMID- 21176382
TI  - [Probability of high resolution full match for human leukocyte antigen loci in
      unrelated donors and recipients with low resolution match].
AB  - This study was aimed to analyze the possibility of high resolution matching for
      human leukocyte antigen (HLA) loci in unrelated donor-recipient pair with low
      resolution match in HLA-A, -B, -DRB1 loci. Samples were genotyped for HLA-A, -B, 
      C, -DRB1 and -DQB1 by polymerase chain reaction sequence based typing (PCR-SBT).
      The results showed that the total number of patients and the donors were 166 and
      274. 97 (58.43%) patients were matched for 1 donor and 47 (28.31%) patients were
      matched for 2 donors at low resolution level; among 274 donor-recipient pairs,
      HLA-A, -B, -C, -DRB1 and -DQB1 loci matching for 6/10, 7/10, 8/10, 9/10 and 10/10
      were 32 (11.68%), 54 (19.71%), 62 (22.63%), 49 (17.88%) and 48 (17.52%)
      respectively; there were mismatch in HLA-A, -B, -C, -DRB1 and -DQB1 loci, and the
      most mismatch was in HLA-C locus. The number of alleles of HLA-A, -B, -C, -DRB1
      and -DQB1 loci were 23, 46, 21, 30 and 17 respectively in the donors. The alleles
      number HLA-A, -B, -C, -DRB1 and -DQB1 loci were 20, 40, 22, 29 and 16
      respectively in the patients; the haplotype number of HLA loci were 311 in the
      donors and 224 in the patients. The high frequency of haplotype was A*02:07
      B*46:01-C*01:02-DRB1*09:01:02-DQB1*03:03 (5.63% and 6.88%). It is concluded that
      the probability of high resolution mismatch of HLA loci is high in unrelated
      donor-recipient pairs with low resolution match in HLA-A, -B, -DRB1 loci.

PMID- 21176383
TI  - [Nucleotide sequence analysis of A novel HLA-B*15:124 allele confirmed].
AB  - This study was purposed to investigate the nucleotide sequences of a novel HLA
      B*15:124 allele and its molecular mechanism. The genomic DNA from whole blood was
      extracted by using commercial DNA extraction kit. The sequences of exon 2, 3 and
      4 of HLA-B locus in the proband were amplified by PCR with group-specific
      primers, the PCR products were purified by enzymes digestion, then exon 2 to 4 of
      HLA-B locus for both orientations was sequenced. The results showed that 2 HLA-B
      alleles of proband were gained after amplification and sequencing of group
      specific primers, among them one was a B*40:03, another was a novel allele. After
      BLAST analysis, the novel allele showed nucleotides different from HLA-B*15:52 in
      exon 3 at nucleotide position 427 A > T and 440 G > T which resulted in amino
      acid change from Thr to Ser at codon 143 and Trp to Leu at conon 147. It is
      concluded that a novel HLA-B allele has two different nucleotides. This HLA-B
      allele is identified and has been officially named B*15:124 by the WHO
      Nomenclature Committee.

PMID- 21176384
TI  - [Detection of fetal short tandem repeat loci in maternal plasma as gender
      independent fetal DNA marker].
AB  - The aim of this study was to investigate the feasibility of using fetal short
      tandem repeat (STR) loci in maternal plasma as gender-independent fetal DNA
      marker. DNA from maternal plasma sample was extracted using QIAamp DNA Kit. AmpF1
      STR profiler box was used to amplify 9 different polymorphic short tandem repeat
      (STR) loci (D3S1358, VWA, FGA, D5S818, D13S317, D7S820, D8S1179, D21S11, D18S51),
      the multiplex fluorescent PCR was used to amplify the STR alleles of fetal DNA in
      36 pregnant plasma samples of pregnant women at different pregnancy. Their
      husbands' DNA isolated from whole blood samples were amplified at the same time.
      The PCR products were electrophoresis by ABI Prism 377 sequencer, the results of
      electrophoresis were analysed by Genscan. The presence of fetal DNA in maternal
      plasma by Paternally inherited fetal alleles were detected. The results showed
      that paternally inherited fetal alleles were detected in 4 cases in early
      pregnancy (4/6), 19 cases in middle pregnancy (19/20) and 9 cases in late
      pregnancy (9/10) respectively, the paternally inherited fetal alleles in 4 of 36
      cases could not be detected. It is concluded that fluorescent multiplex PCR can
      be used for amplification of male and female fetal STRs in maternal plasma to
      obtain genetic information, which may have implication for non-invasive prenatal
      diagnosis of certain hereditary diseases independent of the fetal sex.

PMID- 21176385
TI  - [Research progress on second-hit in malignant lymphomagenesis-- review].
AB  - Stem/progenitor cells contribute to normal development of organs, but their
      mutation may lead to many human diseases including cancer. Stem/progenitor cells
      and some of the cancer cells have the same abilities of self-renewal and
      differentiation, suggesting that tumors were initiated from mutated
      stem/progenitor cells, the cancer stem/progenitor cells. The recent studies on
      the origin of the non-Hodgkin's lymphomas has proved that the second-hit
      aggravates gene mutation in lymphocytic progenitor cells, leading to the
      generation of lymphoma. This review summarizes the current advances in the
      studies of the second-hit at stem/progenitor cells in oncogenesis of B-cell non
      Hodgkin's lymphoma.

PMID- 21176386
TI  - [Advances on pathogenesis research of acute myeloid leukemia with t(8;21)--
      review].
AB  - Acquired chromosomal translocations can be identified in nearly 50% of human
      acute myeloid leukemias. The common chromosomal translocation in this disease is
      t(8;21) (q22;q22). It involves the aml1 (runx1) gene on chromosome 21 and the eto
      (mtg8, runx1t1) gene on chromosome 8 generating the aml1/eto fusion gene. An
      initial model for its pathogenesis emphasized the conversion of a hematopoietic
      transcriptional activator AML1 into a leukemogenic repressor which blocked
      myeloid differentiation at the level of target gene regulation. Aml1/eto fusion
      genes inhibit key hematopoietic transcription factor that function as tumor
      suppressors at several nodal point during hematopoietic differentiation. A new
      model is presented in which aml1/eto coordinates expansion of the stem cell
      compartment with diminished lineage commitment and with genome instability. In
      this review, the molecular role of aml1/eto fusion gene and his transcribed
      isoforms in regulating stem renewal, blocking hematopoietic differentiation and
      interacting with various lineage-specific transcription factors are summarized.

PMID- 21176387
TI  - [RNA interference used for reversal of multi-drug resistance in leukemia cells --
      review].
AB  - Chemotherapy remains at the first line for the treatment of leukemia. However,
      the multi-drug resistance of the tumor cells caused by chemotherapeutic drugs has
      seriously affected the effect of chemotherapy. And this is the main reason for
      the failure of the leukemia treatment. Therefore, to explore an effective way of
      reversing drug resistance has become the key of leukemia treatment. RNA
      interference, a system within living cells, helps to determine which genes are
      active and how active they are. It is a process in which translation of some cell
      messenger RNA (mRNA) sequences is prevented, because of the presence of (and
      consequent destruction of) matching double-stranded RNA sequences. RNA
      interference is also called post-transcriptional gene silencing (PTGS), since its
      effect on gene expression occurs after the production of mRNA during
      transcription. It is believed that RNA interference can protect the cell against
      viruses and other threats. The greatest advantage of RNAi is the specificity and
      high efficiency which can induce suppression of specific genes of interest but
      the unrelated genes are not affected. The selective and robust effect of RNAi on
      gene expression makes it a valuable research tool both in cell culture and living
      organisms because synthetic dsRNA introduced into cells can induce the
      suppression of specific genes of interest. Nowadays, the technology has been
      widely used in biomedical fields, especially in the diagnosis and treatment of
      blood system disease. However, besides the stability, targeting and biological
      safety in genetics, the immune response induced by exogenous RNA is also one of
      the key factors to limit the clinical practice of this emerging technology. In
      this review, the breakthrough of the technology in multi-drug resistance reversal
      in leukemia is summarized with the RNA interference technology as a starting
      point.

PMID- 21176388
TI  - [Multidrug resistance of tumor/progenitor stem cells-- review].
AB  - Tumor Stem/Progenitor Cells are characterized by
      undifferentiation/hypodifferention, self-renewal, differentiation potential,
      which is responsible for tumor occurrence, growth and metastasis. The theory
      about tumor stem/progenitor cells provides a new insight to recognize the origin
      and essence of tumors. Gaining a better insight into the origin of tumor
      stem/progenitor cells and the mechanisms of tumor stem/progenitor cells
      resistance to chemotherapy may lead to new therapeutic targets and better
      anticancer strategies. This review summarizes recent progress of research on the
      origin of tumor stem/progenitor cells and multidrug resistance.

PMID- 21176389
TI  - [Factors influencing leukemic dendritic cell cultivation in vitro-- review].
AB  - Leukemic dendritic cells, compared to normal dendritic cells, have the similar
      surface molecules, but have poor antigen-presenting function. When inoculated in
      the human body, the dendritic cells can not produce enough immune response.
      Therefore, how to make dendritic cells mature and have its own function to play a
      better anti-leukemia immune response is the key problem in clinical treatment.
      And it is one of the hottest studies in the immunotherapy field. This review
      focuses the recent progress of research on the culture of dendritic cells in
      vitro, its influence factors and so on.

PMID- 21176390
TI  - [Leukemia stem/progenitor cells and target therapy for leukemia-- review].
AB  - Human leukemias are considered as clonal malignancies initiated at stage as early
      as hematopoietic stem/progenitor cells. The drug resistance and relapse are two
      major causes for treatment failure of leukemia. Recently, the discovery of
      leukemia stem/progenitor cells (LSPC) and subsequent research have provided a cue
      to elucidate the pathogenesis of leukemia and to explore the strategies of
      targeted therapy against LSPC. This review summarizes the molecular
      characteristics of LSPC and some research advances of therapy targeting LSPC
      including therapy targeting to surface molecules of LSPC, interference of
      interaction between LSPC and bone marrow microenvironment, regulation mechanisms
      of some specific molecular and so on.

PMID- 21176391
TI  - Plasma-induced surface modification of polydimethylsiloxane aimed at reducing
      salt and protein deposition.
AB  - Polydimethylsiloxane (PDMS) is an elastomer that is widely used in construction
      and for biological and biomedical applications. The biocompatibility of PDMS was
      improved by different surface treatment methods, i.e., plasma treatment or a
      combination of plasma treatment with UV-irradiation or redox initiator, to
      minimize the effects of deposition of salts and proteins. In this work we used
      the vinyl monomers sulfobetaine and AMPS which have good biocompatible
      properties. 

PMID- 21176392
TI  - Morphological and histological evaluations of 3D-layered blood vessel constructs
      prepared by hierarchical cell manipulation.
AB  - Three-dimensional (3D)-layered blood vessel constructs consisting of human
      umbilical artery smooth muscle cells (SMCs) and human umbilical vascular
      endothelial cells (ECs) were fabricated by hierarchical cell manipulation, and
      their basic morphology, histology and blood compatibility  were evaluated in
      relation to the EC layers. For the hierarchical cell manipulation, fibronectin
      gelatin (FN-G) nanofilms were prepared on the surface of SMC layers to provide a
      cell adhesive nano-scaffold for the second layer of cells. The layer number of
      blood vessel constructs was easily  controllable from 2 to 7 layers, and the
      histological evaluation, scanning electron microscope (SEM) and transmission
      electron microscope (TEM) observations indicated a hierarchical blood vessel
      analogous morphology. The immunefluorescence staining revealed homogeneous and
      dense tight-junction  of the uppermost EC layer. Furthermore, the nano-meshwork
      morphology of the FN-G films like a native extracellular matrix was observed
      inside the blood vessel constructs by SEM. Moreover, a close association between
      actin microfilaments and the nano-meshworks was observed on the SMC surface  by
      TEM. The blood compatibility of the blood vessel constructs, 4-layered SMC/1
      layered EC (4L-SMC/1L-EC), was clearly confirmed by inhibition of platelet
      adhesion, whereas the blood vessel constructs without EC layers (4L-SMC) showed
      high adhesion and activation of the platelet. The 3D-blood  vessel constructs
      prepared by hierarchical cell manipulation technique will be valuable as a blood
      vessel model in the tissue engineering or pharmaceutical fields.

PMID- 21176393
TI  - Preparation of a silk fibroin spongy wound dressing and its therapeutic
      efficiency in skin defects.
AB  - A novel silk fibroin spongy wound dressing (SFSD) incorporated with nano-Ag
      particles was prepared by coagulating with 1.25-5.0% (v/v) poly(ethylene glycol
      diglycidyl ether) (PGDE). The mechanical properties, moisture permeability and
      hygroscopicity of SFSD, and the nano-Ag release  behavior from SFSD were
      evaluated. The results showed that the soft SFSD had satisfying tensile strength
      and flexibility, as well as excellent moisture permeability and absorption
      capability of wound exudates. The moisture permeability was 101 g/m(2) per h and
      the water absorption  capacity of SFSD was 595.2% and 251.9% of its own weight in
      dry and wet states, respectively. The nano-Ag in the SFSD was released
      continuously at a relatively stable rate in PBS resulting in a remarkable
      antibacterial property. A rabbit model was used to dynamically observe the
      healing process  of full-thickness skin defects. Full-thickness wounds were
      created on the dorsal side of rabbits, which were covered with SFSD and porcine
      acellular dermal matrix (PADM) for comparison. The mean healing time of the
      wounds covered with SFSD was 17.7 +/- 2.4 days, significantly shorter  than that
      with PADM. The histological analysis showed that the epidermal cell layer formed
      with SFSD was very similar to normal skin, suggesting that SFSD may provide a
      good component for the development of new wound dressings.

PMID- 21176394
TI  - Enhancement of wound healing by human multipotent stromal cell conditioned
      medium: the paracrine factors and p38 MAPK activation.
AB  - Wound healing can be improved by transplanting mesenchymal stem cells (MSCs). In
      this study, we have demonstrated the benefits of the conditioned medium derived
      from human MSCs (CM-MSC) in wound healing using an excisional wound model. CM-MSC
      accelerated wound closure with increased reepithelialization, cell infiltration,
      granulation formation, and angiogenesis. Notably, CM-MSC enhanced epithelial and
      endothelial cell migration, suggesting the contribution of increased cell
      migration to wound healing enhanced by CM-MSC. Cytokine array, ELISA analysis,
      and quantitative RT-PCR revealed high levels of IL-6 in CM-MSC. Moreover, IL-6
      added to the preconditioned medium enhanced both cell migration and wound
      healing, and antibodies against IL-6 blocked the increase in cell motility and
      wound closure by CM-MSC. The IL-6 secretory pathway of MSCs was inhibited by
      SB203580, an inhibitor of p38 MAPK or siRNA against p38 MAPK, suggesting IL-6
      secretion by MSCs is mediated through the activation of p38 MAPK. Inactivation of
      p38 MAPK also reduced the expression and production of IL-8 and CXCL1 by MSCs,
      both of which were also demonstrated to enhance cell migration and wound closure.
      Thus, our data suggest MSCs promote wound healing through releasing a repertoire
      of paracrine factors via activation of p38 MAPK, and the CM-MSC may be applied to
      enhance wound healing.

PMID- 21176395
TI  - Replacement of liver parenchyma in analbuminemic rats with allogenic hepatocytes
      is facilitated by intrabone marrow-bone marrow transplantation.
AB  - Although hepatocyte transplantation (HCTx) is expected to become a useful therapy
      for human liver diseases, allogenic hepatocytes still tend to be rejected within
      a short period due to host immunosurveillance. In the present study, we
      investigated the effect of prior bone marrow transplantation  (BMTx) for the
      engraftment of allogenic hepatocytes using the analbuminemic rat transplantation
      model. The hepatocytes of Lewis (LEW) rats were not accepted in the liver of
      retrorsine (RS)/partial hepatectomy (PH)-treated analbuminemic F344 (F344-alb)
      rats, which express the disparate major  histocompatibility complex (MHC) against
      that of LEW rats. Prior BMTx with the LEW bone marrow cells (BMCs) after
      sublethal irradiation achieved acceptance and repopulation of LEW hepatocytes in
      the liver of the RS/PH-treated F344-alb rats, associated with elevation of serum
      albumin. The replacement  of hepatic parenchyma with albumin positive (Alb(+))
      donor hepatocytes and elevation of serum albumin levels were dependent on the
      bone marrow reconstitution by donor BMCs, which was more efficiently achieved by
      intrabone marrow (IBM)-BMTx than by intravenous (IV)-BMTx. Our results 
      demonstrate that efficient bone marrow reconstitution by IBM-BMTx enables the
      replacement of the hepatic parenchyma with allogenic hepatocytes in RS/PH-treated
      analbuminemic rats without immunosuppressants.

PMID- 21176396
TI  - Cell contact accelerates replicative senescence of human mesenchymal stem cells
      independent of telomere shortening and p53 activation: roles of Ras and oxidative
      stress.
AB  - Mesenchymal stem cells (MSCs) are of great therapeutic potentials due to their
      multilineage differentiation capabilities. Before transplantation, in vitro
      culture expansion of MSCs is necessary to get desired cell number. We observed
      that cell contact accelerated replicative senescence  during such process. To
      confirm the finding as well as to investigate the underlying mechanisms, we
      cultured both human bone marrow- and umbilical cord blood-derived MSCs under
      noncontact culture (subculture performed at 60-70% of confluence), or contact
      culture (cell passage performed  at 100% of confluence). It was found that MSCs
      reached cellular senescence earlier in contact culture, and the doubling time was
      significantly prolonged. Marked increase of senescence-associated beta
      galactosidase-positive staining was also observed as a result of cell contact.
      Cell cycle  analysis revealed increased frequency of cell cycle arrest after
      contact culture. It was noted, however, that the telomere length was not altered
      during contact-induced acceleration of senescence. Moreover, cell cycle
      checkpoint regulator P53 expression was not affected by cell contact. Marked 
      increase in intracellular reactive oxygen species (ROS) and a concomitant
      decrease in the activities of antioxidative enzymes were also observed during
      contact-induced senescence. Importantly, increased p16(INK4a) following Ras
      upregulation was found after contact culture. Taken together,  cell contact
      induced accelerated senescence of MSCs, which is telomere shortening and p53
      independent. ROS accumulation due to defective ROS clearance function together
      with Ras and p16(INK4a) upregulation play an important role in contact-induced
      senescence of MSCs. Overconfluence  should therefore be avoided during in vitro
      culture expansion of MSCs in order to maintain their qualities for clinical
      application purposes. The contact-induced senescence model reported in this study
      will serve as a useful model system that allows further study of the molecular
      mechanisms  of senescence in MSCs.

PMID- 21176397
TI  - Simple and highly efficient method for production of endothelial cells from human
      embryonic stem cells.
AB  - Endothelial cells derived from human embryonic stem cells (hESC-ECs) hold much
      promise as a valuable tool for basic vascular research and for medical
      application such as cell transplantation or regenerative medicine. Here we have
      developed an efficient approach for the production of  hESC-ECs. Using a
      differentiation method consisting of a stepwise combination of treatment with
      glycogen synthase kinase-3beta (GSK-3beta) inhibitor and culturing in vascular
      endothelial growth factor (VEGF)-supplemented medium, hESC-ECs are induced in 5
      days with about 20% efficiency.  These cells express vascular endothelial
      cadherin (VE-cadherin), VEGF receptor-2 (VEGFR-2), CD34, and platelet endothelial
      cell adhesion molecule-1 (PECAM-1). These hESC-ECs can then be isolated with 95%
      purity using a magnetic sorting system, and expanded to more than 100-fold within
      a month.  The hESC-ECs thus produced exhibit the endothelial morphological
      characteristics and specific functions such as capillary tube formation and
      acetylated low-density lipoprotein uptake. We propose that our methodology is
      useful for efficient and large-scale production of hESC-ECs.

PMID- 21176398
TI  - Hepatocyte transplantation through the hepatic vein: a new route of cell
      transplantation to the liver.
AB  - The efficiency of hepatocyte transplantation into the liver varies with the
      method of administration. This study investigated whether retrograde infusion via
      the hepatic vein provides a sufficient number of donor cells for the liver. Donor
      hepatocytes were isolated from dipeptidyl peptidase  IV (DPPIV(+)) rats and
      transplanted into DPPIV(-) rat livers either by antegrade portal vein infusion or
      retrograde hepatic vein infusion. Hepatocyte engraftment ratios and localization
      were evaluated by histological DPPIV enzymatic staining at 1 week and 8 weeks
      after  the transplantation. No significant differences in engraftment efficiency
      were observed at either 1 week or 8 weeks after transplantation by either route.
      However, the localization of the transplanted hepatocytes differed with the
      administration route. Portal vein infusion resulted in predominantly  periportal
      engraftment, whereas hepatic vein infusion led to pericentral zone engraftment.
      Immunohistochemical analysis showed that the transplanted hepatocytes engrafted
      in the pericentral zone after retrograde infusion displayed intense CYP2E1
      staining similar to the surrounding native hepatocytes.  CYP2E1 staining was
      further enhanced by administration of isosafrole, an inducing agent for various
      cytochrome P450 enzymes, including CYP2E1. This study demonstrates a novel
      approach of transplanting hepatocytes into the liver through retrograde hepatic
      vein infusion as the means to target  cell implantation to the pericentral zone.

PMID- 21176399
TI  - Strategies for the development of cell lines for ex vivo gene therapy in the
      central nervous system.
AB  - Disorders of the central nervous system (CNS) as a result of trauma or ischemic
      or neurodegenerative processes still pose a challenge for modern medicine. Due to
      the complexity of the CNS, and in spite of the advances in the knowledge of its
      anatomy, pharmacology, and molecular and  cellular biology, treatments for these
      diseases are still limited. The development of cell lines as a source for
      transplantation into the damaged CNS (cell therapy), and more recently their
      genetic modification to favor the expression and delivery of molecules with
      therapeutic potential (ex  vivo gene therapy), are some of the techniques used in
      search of novel restorative strategies. This article reviews the different
      approaches that have been used and perfected during the last decade to generate
      cell lines and their use in experimental models of neuronal damage, and evaluates
      the prospects of applying these methods to treat CNS disorders.

PMID- 21176400
TI  - Mesoangioblasts from facioscapulohumeral muscular dystrophy display in vivo a
      variable myogenic ability predictable by their in vitro behavior.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is the third most frequent
      inherited myopathy. We previously demonstrated that mesoangioblasts can be
      efficiently isolated from FSHD muscles, although their differentiation ability
      into skeletal muscle was variably impaired. This correlates  with overall disease
      severity and degree of histopathologic abnormalities, since mesoangioblasts from
      morphologically normal muscles did not show any myogenic differentiation block.
      The aim of our present study was to verify whether mesoangioblasts from
      differentially affected FSHD muscles  reproduce in vivo the same differentiation
      ability shown in vitro by studying their capability to form new muscle fibers
      during muscle regeneration of experimentally damaged muscles. We show that a
      diverse ability of FSHD mesoangioblasts to engraft and differentiate into
      skeletal muscle of  SCID mice is strictly related to the characteristics of the
      muscle of origin, closely replicating in vivo what was previously observed in
      vitro. Moreover, we demonstrate that mesoangioblasts obtained from severely
      affected muscles scarcely integrate into muscle fibers, remaining mainly
      localized  in the connective tissue. This suggests a defective migration in
      response to chemoattractants released by damaged fibers, as indicated by cell
      migration assays in response to HMGB1 and very low levels of RAGE expression,
      along with a decreased ability to fuse or to appropriately trigger the  myogenic
      program. Our study indicates that FSHD mesoangioblasts from unaffected muscles
      can be used as selective treatment to halt muscle degeneration in severely
      affected muscles, and suggests that pharmacological and molecular interventions
      aimed to ameliorate homing and engraftment of transplanted  autologous
      mesoangioblasts may open the way to cell therapy for FSHD patients, without
      requiring immunosuppression or genetic correction in vitro.

PMID- 21176402
TI  - Multitract microtransplantation increases the yield of DARPP-32-positive
      embryonic striatal cells in a rodent model of Huntington's disease.
AB  - Embryonic striatal graft-mediated functional recovery in the rodent lesion model
      of Huntington's disease (HD) has been shown to correlate with the proportion of
      dopamine- and adenosine 3',5'-monophosphate-regulated phosphoprotein with a
      molecular weight of 32 kDa (DARPP-32)-positive  neurons in the graft. The current
      study investigated the impact of graft distribution on the yield of DARPP-32
      positive cells in the grafts following either single-tract or multitract cell
      delivery protocols using the microtransplantation approach. Cells derived from
      the whole ganglionic eminence  of E15 rat embryos, ubiquitously expressing green
      fluorescent protein (GFP), were implanted into unilaterally QA-lesioned rat
      striatum either as 2 * 1.8 MUl macrodeposits in a single tract, or as 18 * 0.2
      MUl microdeposits disseminated over six needle, multitract, penetrations.  For
      both groups, an ultrathin glass capillary with an outer diameter of 50 MUm was
      used. Histological assessment at 4 months after transplantation showed nearly
      twofold increase of DARRP-32-positive striatal-like neurons in the multitract
      compared to the single-tract group. However, the  cellular make-up of the grafts
      did not translate into functional differences as tested in a basic spontaneous
      behavior test. Furthermore, the volumetric values for overall volume, DARPP-32
      positive patches, and dopaminergic projection zones were similar between both
      groups. The results show  that distribution of fetal striatal tissue in multiple
      submicroliter deposits provides for an increased yield of striatal-like neurons,
      potentially due to the enlargement of the graft-host border area intensifying the
      graft's exposure to host-derived factors. Furthermore, the use of  embryonic
      tissue from GFP donors was validated in cell-based therapy studies in the HD
      model.

PMID- 21176401
TI  - The sequential combination of a JNK inhibitor and simvastatin protects porcine
      islets from peritransplant apoptosis and inflammation.
AB  - Intraductal administration of a c-Jun NH(2)-terminal kinase (JNK) inhibitor
      enhances islet viability. However, its role in reducing the inflammatory response
      in islets is unknown. It is also unknown whether a JNK inhibitor could act in
      synergy with statins. We examined if the  sequential combination of a JNK
      inhibitor and simvastatin would reduce islet inflammation and improve islet
      viability. We performed porcine islet isolation with or without intraductal
      administration of SP600125, a JNK inhibitor. This was followed by culture medium
      supplementation with either  nicotinamide alone or nicotinamide plus simvastatin.
      We assessed the viability of islets by flow cytometry, islet loss during
      overnight culture, graft function in NOD/SCID mice, and expression of
      inflammation-related genes in islets. The sequential combination of a JNK
      inhibitor and simvastatin  increased the beta-cell viability index of porcine
      islets cultured overnight (p = 0.015) as well as islet viability as assessed by a
      DNA binding dye staining (p = 0.011). The combination of a JNK inhibitor and
      simvastatin significantly increased the islet survival rate (p  = 0.027) when the
      histomorphometry of donor pancreas indicated a large islet proportion of greater
      than 50.55%. When we transplanted the same islet mass per recipient for each
      group, there was no difference in overall islet graft function. Intraductal
      administration of JNK inhibitor significantly  suppressed mRNA expression levels
      of interleukin-1beta (IL-1beta), interferon-gamma, tumor necrosis factor-alpha,
      IL-6, IL-8, and macrophage chemoattractant protein-1. It also decreased the
      concentration of IL-1beta (p = 0.040) and IL-8 (p = 0.023) in the culture
      supernatant.  In conclusion, the sequential combination of a JNK inhibitor and
      simvastatin protected porcine islets from peritransplant apoptosis. Inhibition of
      JNK reduced the inflammatory response and could be considered an alternative
      target for suppression of porcine islet inflammation.

PMID- 21176403
TI  - Human umbilical cord blood-derived mesenchymal stem cells protect against
      neuronal cell death and ameliorate motor deficits in Niemann Pick type C1 mice.
AB  - Niemann Pick disease type C1 (NPC) is an autosomal recessive disease
      characterized by progressive neurological deterioration leading to premature
      death. In this study, we hypothesized that human umbilical cord blood-derived
      mesenchymal stem cells (hUCB-MSCs) have the multifunctional  abilities to
      ameliorate NPC symptoms in the brain. To test this hypothesis, hUCB-MSCs were
      transplanted into the hippocampus of NPC mice in the early asymptomatic stage.
      This transplantation resulted in the recovery of motor function in the Rota Rod
      test and impaired cholesterol homeostasis  leading to increased levels of
      cholesterol efflux-related genes such as LXRalpha, ABCA1, and ABCG5 while
      decreased levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase were observed
      in NPC mice. In the cerebrum, hUCB-MSCs enhanced neuronal cell survival and
      proliferation, where they  directly differentiated into electrically active MAP2
      positive neurons as demonstrated by whole-cell patch clamping. In addition, we
      observed that hUCB-MSCs reduced Purkinje neuronal loss by suppression of
      inflammatory and apoptotic signaling in the cerebellum as shown by
      immunohistochemistry.  We further investigated how hUCB-MSCs enhance cellular
      survival and inhibit apoptosis in NPC mice. Neuronal cell survival was associated
      with increased PI3K/AKT and JAK2/STAT3 signaling; moreover, hUCB-MSCs modulated
      the levels of GABA/glutamate transporters such as GAT1, EAAT2, EAAT3, and  GAD6
      in NPC mice as assessed by Western blot analysis. Taken together, our findings
      suggest that hUCB-MSCs might play multifunctional roles in neuronal cell survival
      and ameliorating motor deficits of NPC mice.

PMID- 21176404
TI  - The secretory profiles of cultured human articular chondrocytes and mesenchymal
      stem cells: implications for autologous cell transplantation strategies.
AB  - This study was undertaken to compare the phenotype of human articular
      chondrocytes (ACs) and bone marrow-derived mesenchymal stem cells (MSCs) after
      cell expansion by studying the spectrum of proteins secreted by cells into the
      culture medium. ACs and MSCs were expanded in monolayer  cultures for some weeks,
      as done in standard cell transplantation procedures. Initially, the expression of
      cartilage signature genes was compared by real-time PCR. Metabolic labeling of
      proteins (SILAC) in combination with mass spectrometry (LC/MS-MS) was applied to
      investigate differences  in released proteins. In addition, multiplex assays were
      carried out to quantify the amounts of several matrix metalloproteases (MMPs) and
      their natural inhibitors (TIMPs). Expanded chondrocytes showed a slightly higher
      expression of cartilage-specific genes than MSCs, whereas the overall  spectra of
      released proteins were very similar for the two cell types. In qualitative terms
      MSCs seemed to secrete similar number of extracellular matrix proteins (43% vs.
      45% of total proteins found) and catabolic agents (9% vs. 10%), and higher number
      of anabolic agents (12 % vs. 7%) compared  to ACs. Some matrix-regulatory agents
      such as serpins, BMP-1, and galectins were detected only in MSC supernatants.
      Quantitative analyses of MMPs and TIMPs revealed significantly higher levels of
      MMP-1, MMP-2, MMP-3, and MMP-7 in the medium of ACs. Our data show that after the
      expansion phase,  both ACs and MSCs express a dedifferentiated phenotype,
      resembling each other. ACs hold a phenotype closer to native cartilage at the
      gene expression level, whereas MSCs show a more anabolic profile by looking at
      the released proteins pattern. Our data together with the inherent capability  of
      MSCs to maintain their differentiation potential for longer cultivation periods
      would favor the use of these cells for cartilage reconstruction.

PMID- 21176405
TI  - Inhibition of T-cell proliferation by murine multipotent mesenchymal stromal
      cells is mediated by CD39 expression and adenosine generation.
AB  - Multipotent mesenchymal stromal cells (MSCs) are bone marrow-derived cells of
      nonhematopoietic origin with immunoregulatory properties. Although some functions
      of MSCs have been identified, there are still features that are not explained
      thus far. The aim of the present study was to  identify novel factors involved in
      MSC-mediated inhibition of T-cell proliferation. We here demonstrate that the
      surface molecule CD39 is coexpressed in concert with CD73 on murine MSCs
      catalyzing the generation of adenosine, which can directly act on activated T
      cells via the adenosine A2A  receptor. Blocking of the adenosine pathway either
      by the A2A receptor antagonist SCH58261 or the specific CD39 inhibitor
      polyoxotungstate 1 (POM-1) blocked MSC-mediated suppression of T-cell
      proliferation almost completely. We conclude that CD39/CD73 coexpression is a
      novel important component  of the immunoregulatory functions of murine MSCs. Our
      findings may both be important to improve our understanding of MSC function and
      for the development of immunomodulatory cellular therapies.

PMID- 21176406
TI  - Effects of acute cytomegalovirus infection on rat islet allograft survival.
AB  - Transplantation of pancreatic islets is a promising therapy for the treatment of
      type 1 diabetes mellitus. However, long-term islet graft survival rates are still
      unsatisfactory low. In this study we investigated the role of cytomegalovirus
      (CMV) in islet allograft failure. STZ-diabetic  rats received an allogenic islet
      graft in combination with either an acute CMV infection or control infection. A
      third group received ganciclovir treatment in addition to the CMV infection.
      Graft function was assessed by measuring basal blood glucose levels. After
      sacrifice, the islet grafts  were retrieved for analysis of infection and
      leukocyte infiltration. CMV-infected recipients demonstrated accelerated islet
      graft failure compared to noninfected controls. CMV infection of the graft was
      only observed prior to complete graft failure. Quantification of the leukocyte
      infiltration  demonstrated increased CD8(+) T-cell and NK cell infiltration in
      the CMV-infected grafts compared to the controls. This suggests that CMV
      infection accelerates immune-mediated graft destruction. Antiviral ganciclovir
      treatment did not prevent accelerated graft failure, despite effectively 
      decreasing the grade of infection. Our data confirm the recently published CITR
      data, which state that CMV is an independent risk factor for failure of islet
      grafts. Also, our data demonstrate that new approaches for preventing virus
      induced islet allograft failure may be required.

PMID- 21176407
TI  - Local transplantation of G-CSF-mobilized CD34(+) cells in a patient with tibial
      nonunion: a case report.
AB  - Although implantation of crude bone marrow cells has been applied in a small
      number of patients for fracture healing, transplantation of peripheral blood
      CD34(+) cells, the hematopoietic/endothelial progenitor cell-enriched population,
      in patients with fracture has never been  reported. Here, we report the first
      case of tibial nonunion receiving autologous, granulocyte colony stimulating
      factor mobilized CD34(+) cells accompanied with autologous bone grafting. No
      serious adverse event occurred, and the novel therapy performed 9 months after
      the primary  operation resulted in bone union 3 months later without any symptoms
      including pain and gait disturbance.

PMID- 21176408
TI  - Biological and physicochemical characterization of a serum- and xeno-free
      chemically defined cryopreservation procedure for adult human progenitor cells.
AB  - While therapeutic cell transplantations using progenitor cells are increasingly
      evolving towards phase I and II clinical trials and chemically defined cell
      culture is established, standardization in biobanking is still in the stage of
      infancy. In this study, the EU FP6-funded CRYSTAL  (CRYo-banking of Stem cells
      for human Therapeutic AppLication) consortium aimed to validate novel Standard
      Operating Procedures (SOPs) to perform and validate xeno-free and chemically
      defined cryopreservation of human progenitor cells and to reduce the amount of
      the potentially toxic cryoprotectant  additive (CPA) dimethyl sulfoxide (DMSO).
      To achieve this goal, three human adult progenitor and stem cell populations
      umbilical cord blood (UCB)-derived erythroid cells (UCB-ECs), UCB-derived
      endothelial colony forming cells (UCB-ECFCs), and adipose tissue (AT)-derived
      mesenchymal stromal  cells (AT-MSCs)-were cryopreserved in chemically defined
      medium supplemented with 10% or 5% DMSO. Cell recovery, cell repopulation, and
      functionality were evaluated postthaw in comparison to cryopreservation in
      standard fetal bovine serum (FBS)-containing freezing medium. Even with a 
      reduction of the DMSO CPA to 5%, postthaw cell count and viability assays
      indicated no overall significant difference versus standard cryomedium.
      Additionally, to compare cellular morphology/membrane integrity and ice crystal
      formation during cryopreservation, multiphoton laser-scanning cryomicroscopy 
      (cryo-MPLSM) and scanning electron microscopy (SEM) were used. Neither cryo-MPLSM
      nor SEM indicated differences in membrane integrity for the tested cell
      populations under various conditions. Moreover, no influence was observed on
      functional properties of the cells following cryopreservation  in chemically
      defined freezing medium, except for UCB-ECs, which showed a significantly reduced
      differentiation capacity after cryopreservation in chemically defined medium
      supplemented with 5% DMSO. In summary, these results demonstrate the feasibility
      and robustness of standardized xeno-free  cryopreservation of different human
      progenitor cells and encourage their use even more in the field of tissue
      engineering and regenerative medicine.

PMID- 21176409
TI  - Collagen IV significantly enhances migration and transplantation of embryonic
      stem cells: involvement of alpha2beta1 integrin-mediated actin remodeling.
AB  - Embryonic stem (ES) cell transplantation represents a potential means for the
      treatment of degenerative diseases and injuries. As appropriate distribution of
      transplanted ES cells in the host tissue is critical for successful
      transplantation, the exploration of efficient strategies to enhance ES cell
      migration is warranted. In this study we investigated ES cell migration under the
      influence of various extracellular matrix (ECM) proteins, which have been shown
      to stimulate cell migration in various cell models with unclear effects on ES
      cells. Using two mouse ES (mES) cell lines, ESC 26GJ9012-8-2 and ES-D3 GL, to
      generate embryoid bodies (EBs), we examined the migration of differentiating
      cells from EBs that were delivered onto culture surfaces coated with or without
      collagen I, collagen IV, Matrigel, fibronectin, and laminin. Among these ECM
      proteins, collagen IV exhibited maximal migration enhancing effect. mES cells
      expressed alpha2 and beta1 integrin subunits and the migration enhancing effect
      of collagen IV was prevented by RGD peptides as well as antibodies against alpha2
      and beta1 integrins, indicating that the enhancing effect of collagen IV on cell
      migration was mediated by alpha2beta1 integrin. Furthermore, staining of actin
      cytoskeleton that links to integrins revealed well-developed stress fibers and
      long filopodia in mES cells cultured on collagen IV, and the actin-disrupting
      cytochalasin D abolished the collagen IV-enhanced cell migration. In addition,
      pretreatment of undifferentiated or differentiated mES cells with collagen IV
      resulted in improved engraftment and growth after transplantation into the
      subcutaneous tissue of nude mice. Finally, collagen IV pretreatment of
      osteogenically differentiated mES cells increased osteogenic differentiation-like
      tissue and decreased undifferentiation-like tissue in the grafts grown after
      transplantation. Our results demonstrated that collagen IV significantly enhanced
      the migration of differentiating ES cells through alpha2beta1 integrin-mediated
      actin remodeling and could promote ES cell transplantation efficiency, which may
      be imperative to stem cell therapy.

PMID- 21176410
TI  - Chronic diseases and mortality in Canadian Aboriginal peoples: learning from the
      knowledge.
AB  - It is a sad fact that Canada's Aboriginal people, whether living in rural
      communities or in urban centers, have a significantly lower life expectancy than
      non-Aboriginal Canadians.1a The gap in health status of Canada's Aboriginal
      peoples is a matter of ongoing concern;2 recognizing and understanding the social
      determinants of health is key to understanding the difference in health status
      and, in my view, key to achieving success in addressing and correcting this
      problem. However, it is important to realize that there are unique social
      determinants for Aboriginal peoples associated with their cultures, histories and
      colonization, and the current social, economic, political and geographic context.

PMID- 21176411
TI  - Mortality of urban Aboriginal adults in Canada, 1991-2001.
AB  - OBJECTIVE: To compare mortality patterns for urban Aboriginal adults with those
      of urban non-Aboriginal adults. METHODS: Using the 1991-2001 Canadian census
      mortality follow-up study, our study tracked mortality to December 31, 2001,
      among a 15% sample of adults, including 16 300 Aboriginal and 2 062 700 non
      Aboriginal persons residing in urban areas on June 4, 1991. The Aboriginal
      population was defined by ethnic origin (ancestry), Registered Indian status
      and/or membership in an Indian band or First Nation, since the 1991 census did
      not collect information on Aboriginal identity. RESULTS: Compared to urban non
      Aboriginal men and women, remaining life expectancy at age 25 years was 4.7 years
      and 6.5 years shorter for urban Aboriginal men and women, respectively. Mortality
      rate ratios for urban Aboriginal men and women were particularly elevated for
      alcohol-related deaths, motor vehicle accidents and infectious diseases,
      including HIV/AIDS. For most causes of death, urban Aboriginal adults had higher
      mortality rates compared to other urban residents. Socio-economic status played
      an important role in explaining these disparities. CONCLUSION: Results from this
      study help fill a data gap on mortality information of urban Aboriginal people of
      Canada.

PMID- 21176412
TI  - Arthritis in the Canadian Aboriginal population: North-South differences in
      prevalence and correlates.
AB  - BACKGROUND: Information on arthritis and other musculoskeletal disorders among
      Aboriginal people is sparse. Survey data show that arthritis and rheumatism are
      among the most commonly reported chronic conditions and their prevalence is
      higher than among non-Aboriginal people. OBJECTIVE: To describe the burden of
      arthritis among Aboriginal people in northern Canada and demonstrate the public
      health significance and social impact of the disease. METHODS: Using cross
      sectional data from more than 29 000 Aboriginal people aged 15 years and over who
      participated in the Aboriginal Peoples Survey 2006, we assessed regional
      differences in the prevalence of arthritis and its association with other risk
      factors, co-morbidity and health care use. RESULTS: The prevalence of arthritis
      in the three northern territories ("North") is 12.7% compared to 20.1% in the
      provinces ("South") and is higher among females than males in both the North and
      South. The prevalence among Inuit is lower than among other Aboriginal groups.
      Individuals with arthritis are more likely to smoke, be obese, have concurrent
      chronic diseases, and are less likely to be employed. Aboriginal people with
      arthritis utilized the health care system more often than those without the
      disease. CONCLUSION: Aboriginal-specific findings on arthritis and other chronic
      diseases as well as recognition of regional differences between North and South
      will enhance program planning and help identify new priorities in health
      promotion.

PMID- 21176413
TI  - The role of public health in addressing child maltreatment in Canada.
AB  - Child maltreatment is a significant health and social issue given its prevalence
      across the general population and the significant short- and long-term outcomes
      associated with maltreatment in childhood. There is a need for a comprehensive,
      collaborative and multisectoral approach for identification, prevention and
      intervention of this complex issue. Within this multisectoral collaboration, it
      is essential for public health in Canada to define its role in addressing and
      preventing child maltreatment. This commentary summarizes how public health can
      address the issue of child maltreatment in Canada by specifically: 1) measuring
      the magnitude of maltreatment through public health surveillance systems such as
      the Canadian Incidence Study of Reported Child Abuse and Neglect; 2) identifying
      modifiable risk factors; 3) identifying and evaluating community-based
      interventions to prevent violence; and 4) implementing evidence-based primary
      prevention strategies.

PMID- 21176414
TI  - Executive summary--performance monitoring for cervical cancer screening programs
      in Canada.
AB  - The purpose of this report is to define a core set of performance indicators for
      organized cervical cancer screening programs in Canada. The goals for
      establishing a pan-Canadian set of performance indicators are to promote high
      quality screening through monitoring and evaluation. Over time, with regular
      monitoring and reporting of these indicators, an evidence base will grow which
      will permit the setting of pan-Canadian targets.

PMID- 21176415
TI  - Executive summary--report from the Canadian Chronic Disease Surveillance System:
      hypertension in Canada, 2010.

PMID- 21176416
TI  - Fibromyalgia - a challenge for health care systems or: don't leave the physician
      out in the cold.

PMID- 21176417
TI  - How important are the psychological aspects in fibromyalgic syndrome?

PMID- 21176421
TI  - Holocaust survivors: the pain behind the agony. Increased prevalence of
      fibromyalgia among Holocaust survivors.
AB  - OBJECTIVES: To assess the frequency of fibromyalgia among a population of
      Holocaust survivors in Israel as well as the occurrence of post-traumatic stress
      disorder (PTSD) and concurrent psychiatric symptoms, including depression and
      anxiety among survivors. METHODS: Eighty-three survivors of the Nazi Holocaust
      and 65 age-matched individuals not exposed to Nazi occupation were recruited.
      Physical examination and manual tender point assessment was performed for the
      establishment of the diagnosis of fibromyalgia and information was collected
      regarding quality of life (SF-36), physical function and health (FIQ),
      psychiatric symptoms (SCL-90) and PTSD symptoms (CAPS). RESULTS: Significantly
      increased rates of fibromyalgia were identified among Holocaust survivors
      compared with controls (23.81% vs. 10.94, p<0.05). Significantly increased rates
      of posttraumatic symptoms and measures of mental distress were also identified
      among survivors. CONCLUSIONS: The results indicate a significantly increased
      prevalence of fibromyalgia among Holocaust survivors six decades after the end of
      the Second World War. This finding furthers our knowledge regarding the long-term
      effect of stress on the development of fibromyalgia.

PMID- 21176420
TI  - Fibromyalgia in patients with ankylosing spondylitis: prevalence and utility of
      the measures of activity, function and radiological damage.
AB  - OBJECTIVES: To determine the prevalence of fibromyalgia (FM) in ankylosing
      spondylitis (AS). To evaluate the effect of FM on the measures of activity in AS.
      To analyse predictive factors in order to identify this group of patients.
      PATIENTS AND METHODS: A cross-sectional study based on 462 patients with definite
      ankylosing spondylitis included in the REGISPONSER. Sociodemographic data,
      clinical features, Bath AS disease activity index (BASDAI), Bath AS functional
      index (BASFI), Bath AS radiology index (BASRI), Stoke modified index (Sasss-m),
      laboratory data, Short-Format 12 (SF-12), AS specific quality of life (ASQoL),
      Fibromyalgia Impact Questionnaire (FIQ) and treatments used were all documented.
      To diagnose FM, the ACR 1990 criteria had to be fulfilled. All statistical tests
      were performed using STATA. RESULTS: The prevalence of fibromyalgia in all AS was
      4.11%. Among the women with AS, the prevalence of FM increased to 10.83%. The
      BASDAI, BASFI and total BASRI were strongly influenced by the presence of FM. The
      inverse relationship between BASDAI or BASFI and total BASRI was taken to
      generate a ratio. Accordingly, if the patient presented BASDAI/BASRI >=1.5 or
      BASFI/BASRI >=1.08, the probability of having FM was very high. CONCLUSIONS:
      There is an increased risk of FM in females with AS. The fact of having FM
      distorts the measures of activity and functional damage of AS. As a result, it is
      possible that some patients with AS and FM are being overtreated. The
      BASDAI/BASRI and BASFI/BASRI ratios are very useful to identify these patients.

PMID- 21176422
TI  - Physical function interfering with pain and symptoms in fibromyalgia patients.
AB  - OBJECTIVES: The aim of this study was to assess the relationship between
      variables of physical assessment - muscular strength, flexibility and dynamic
      balance - with pain, pain threshold, and fibromyalgia symptoms (FM). METHODS: Our
      sample consists of 55 women, with age ranging from 30 to 55 years (mean of 46.5,
      (standard deviation, SD=6.6)), mean body mass index (BMI) of 28.7 (3.8) and
      diagnosed for FM according to the American College of Rheumatology criteria. Pain
      intensity was measured using a visual analogue scale (VAS) and pain threshold
      (PT) using Fisher's dolorimeter. FM symptoms were assessed by the Fibromyalgia
      Impact Questionnaire (FIQ); flexibility by the third finger to floor test (3FF);
      the muscular strength index (MSI) by the maximum volunteer isometric contraction
      at flexion and extension of right knee and elbow using a force transducer,
      dynamic balance by the time to get up and go (TUG) test and the functional reach
      test (FRT). Data were analysed using Pearson's correlation, as well as simple and
      multivariate regression tests, with significance level of 5%. RESULTS: PT and FIQ
      were weakly but significantly correlated with the TUG, MSI and 3FF as well as VAS
      with the TUG and MSI (p<0.05). VAS, PT and FIQ was not correlated with FRT.
      Simple regression suggests that, alone, TUG, FR, MSI and 3FF are low predictors
      of VAS, PT and FIQ. For the VAS, the best predictive model includes TUG and MSI,
      explaining 12.6% of pain variability. For TP and total symptoms, as obtained by
      the FIQ, most predictive model includes 3FF and MSI, which respectively respond
      by 30% and 21% of the variability. CONCLUSIONS: Muscular strength, flexibility
      and balance are associated with pain, pain threshold, and symptoms in FM
      patients.

PMID- 21176423
TI  - Health economic evaluation of outpatient management of fibromyalgia patients and
      the costs avoided by diagnosing fibromyalgia in France.
AB  - OBJECTIVES: To assess whether the decrease in medical resource use and cost after
      diagnosing fibromyalgia, observed in a large primary care population in the
      United Kingdom can be extrapolated to France. METHODS: A questionnaire was
      created based on medical resource use by 2,260 patients diagnosed with
      fibromyalgia between 01/01/1998 and 31/03/2003 in the General Practice Research
      Database in the UK. Sixty French experts (general practitioners, rheumatologists)
      assessed whether the data from that database are in line with their clinical
      practice and, if not, were asked to provide data reflecting their own experience.
      The evaluation period went from 4 years before to 4 years after diagnosis using 1
      year cross-sections. Evaluated resources were drug use, diagnostics tests,
      general practitioners and specialist visits, and also paramedical or alternative
      treatments. Data regarding inpatient care and productivity loss were not
      collected. Medical resource use if no diagnosis had been established was
      estimated, so the impact of diagnosis could be evaluated. RESULTS: Whereas costs
      gradually increase before diagnosis, stagnation in costs occurs in the year after
      diagnosis, followed by a moderate decrease afterwards. The same trend was
      observed whether the panel consisted of general practitioners or rheumatologists.
      The savings made as a result of fibromyalgia diagnosis add up to 126 euros per
      patient per year for the health care payer. General practitioner visits,
      diagnostic tests and drug use represent respectively 57%, 23% and 12% of the
      savings. CONCLUSIONS: Also in France, early diagnosis of fibromyalgia leads to a
      decrease in resource use and health care costs.

PMID- 21176424
TI  - Arterial stiffness and proinflammatory cytokines in fibromyalgia syndrome.
AB  - OBJECTIVES: We assessed arterial stiffness and inflammatory cytokine profiles in
      fibromyalgia syndrome (FMS) patients and analysed the association between them.
      METHODS: Twenty-seven FMS patients and 29 age-matched premenopausal healthy
      controls were enrolled in this study. Arterial stiffness was assessed by pulse
      wave velocity (PWV) and augmentation index (AIx) from pulse waveform analysis.
      Levels of serum interleukin-1beta (IL-1beta), IL-6, IL-8, and vascular
      endothelial growth factor (VEGF) were measured by enzyme-linked immunosorbent
      assay, and a colorimetric assay was used for measurement of serum nitric oxide
      (NO) metabolites (nitrate and nitrite, NOx) level. Statistical analyses included
      the Mann-Whitney U-test and Spearman's correlation coefficient analysis. RESULTS:
      Higher AIx and AIx@HR75 (aortic AIx at a heart rate of 75 beats/min) were noted
      in FMS compared to those in the controls after adjustment using covariants
      (p(adj)=0.023 and p(adj)<0.001). However, there were no differences between the
      three regional PWVs of the two groups at the aorta-femoral, femoral-dorsalis, and
      aorta-radialis arteries (p(adj)>0.05 for all). FMS subjects had significantly
      higher serum IL-8 levels than did the healthy controls (327.9+/-588.7 vs. 76.4+/
      90.5, p(adj)=0.041). However, there were no significant differences in serum IL
      1beta, IL-6, VEGF, or NOx levels between the FMS patients and the controls
      (p(adj)>0.05 of all). Serum IL-8 level did not correlate with PWV and AIx in FMS
      patients. CONCLUSIONS: This study demonstrates higher AIx and IL-8 levels in FMS
      subjects compared to those of the controls. However, arterial stiffness including
      AIx in FMS was not determined by the serum IL-8 level.

PMID- 21176425
TI  - Handgrip strength in men with fibromyalgia.
AB  - OBJECTIVES: To examine the association of muscular strength, as measured by
      handgrip strength test (HGs), with the presence/absence of fibromyalgia (FM) and
      FM severity in men. METHODS: A total of 20 men (age, (mean age+/-standard
      deviation) of 48.0+/-8.0 years) with FM and 60 healthy subjects (age, 49.5+/-7.3
      years) participated in the study. The HGs was measured by a maximal isometric
      test using a dynamometer with adjustable grip in both hands, and the average
      score was used in the analysis. All FM patients completed the Spanish version of
      the Fibromyalgia Impact Questionnaire (FIQ). Patients were classified as having
      moderate FM if the FIQ was <70 and as having severe FM if the FIQ was >=70.
      RESULTS: HGs was ~17% lower in FM patients compared to healthy men (p=0.005) and
      ~27% lower in men with severe FM compared to those with moderate FM (p=0.03). Age
      adjusted logistic regression models showed that 1 kilogram increment in HGs was
      associated with an 8% reduced risk of having FM (OR=0.92, 95% CI: 0.86-0.97,
      p=0.002). In the FM group, 1 kilogram increment in HGs was associated with a 13%
      reduced risk for having severe FM (OR=0.87, 95% CI: 0.76-0.99, p=0.04). HGs was
      negatively associated with pain, fatigue, stiffness and with the total score from
      the FIQ (all p<0.05). CONCLUSIONS: HGs is reduced in male FM patients and is
      inversely related to FM severity and symptomatology. HGs testing could be used as
      a complementary tool in the assessment and monitoring of FM. Further research on
      male FM patients is needed to confirm or contrast these findings.

PMID- 21176426
TI  - Fatigue in Sjogren's syndrome: relationship with fibromyalgia, clinical and
      biologic features.
AB  - More than two third of patients with primary Sjogren's syndrome (SS) report
      fatigue. Despite its clinical relevance, only a few studies have examined the
      relationship of fatigue with the presence of an overlapping Fibromyalgia (FM) and
      other clinical and biological variables. The aim of this study was to assess the
      relationship between fatigue and SS disease activity and damage, FM, widespread
      pain, and mood disorders; finally, the possible correlation between fatigue and a
      panel of cytokines likely to drive the immunopathological process of the disease
      has been examined. Thirty-five female patients with primary SS were consecutively
      enrolled; for each patient the Sjogren's Syndrome Disease Damage Index (SSDDI)
      and the Sjogren's Syndrome Disease Activity Index (SSDAI) were calculated.
      Patients rated pain, fatigue and disease activity using a 100-mm VAS and
      completed Health Assessment Questionnaire (HAQ), the Zung depression (ZSDS) and
      anxiety scales (ZSAS). 30/35 patients (85.7%) felt unduly tired and the same
      percentage of patients suffered with pain in more than one area of the body. 7
      patients satisfied ACR criteria for FM, representing 20% of the whole cohort and
      23% of SS patients with fatigue. No differences were found in disease duration,
      SSDDI, SSDAI, ZSDS and ZSAS among SS patient with or without FM. In the whole
      group, fatigue VAS correlated with HAQ, ZSAS, ZSDS and pain VAS but not with age,
      disease duration, presence and severity of arthritis, SSDDI, SSDAI, or cytokines.
      In conclusion, an overlapping FM can contribute to, but does not entirely account
      for fatigue in Italian patients with primary SS.

PMID- 21176427
TI  - Development of the Fibromyalgia Burden Assessment: measuring the multifaceted
      burden of fibromyalgia.
AB  - OBJECTIVES: To develop a questionnaire assessing the burden of fibromyalgia's
      impacts on patients' lives. METHODS: A literature review was conducted to
      identify impacts of fibromyalgia and their consequences on patients' lives.
      Exploratory interviews were performed with 15 fibromyalgia patients in France,
      Germany and Spain. Using patients' wording, items were generated simultaneously
      in French, German, Spanish, and UK English. Relevance and comprehension of the
      resulting questionnaire versions were tested with 21 additional fibromyalgia
      patients; questionnaires were revised accordingly. RESULTS: Three domains, Burden
      associated with the impacts of fibromyalgia, Symptoms and Influencing factors,
      were identified from the literature review. Following patient interviews, the
      burden domain was further divided based on the nature of the impact: Pain,
      Physical impact (including tiredness, sleep problems and other symptoms),
      Activities of Daily Living impact (including autonomy and coping), Social and
      Family Life impact, Work, Studies and Personal Finances impact, Psychological
      impact (including cognitive impact), and Relationship to Medicine and Disease.
      The resulting test versions of the questionnaire contained 79 items.
      Comprehension tests identified problematic items and cultural differences and
      suggested deletions or rewording. After revision and linguistic harmonization,
      the pilot version of the questionnaire contained 62 items divided into 7
      sections, and was named Fibromyalgia Burden Assessment (FMBA(c)). CONCLUSIONS:
      The FMBA is a self-reported questionnaire allowing the assessment and a better
      understanding of the impacts of fibromyalgia and the burden associated with these
      on patients' daily lives. It is available in UK English, French, German and
      Spanish. Its scoring and validation remain to be undertaken.

PMID- 21176428
TI  - Spasmophilia comorbidity in fibromyalgia syndrome.
AB  - OBJECTIVES: To evaluate the role of spasmophilia (SP) in fibromyalgia syndrome
      (FM). METHODS: Three hundred and fourteen patients (280 F, 34 M) with a diagnosis
      of FM or FM and spasmophilia (FM+SP) were recruited. Clinical assessment of
      patients and controls included the Questionnaires FIQ, HAQ and the tender point
      (TP) count. Life-time or ongoing psychiatric aspects were evaluated by trained
      psychiatrists by means of the classic scales: Structured Clinical Interview
      (SCID) for DSM-IV. The following analysis were evaluated: cytokine (IL1, IL2,
      IL6, IL8, IL10), TNF-alpha, cortisol, GH, ACTH, IGF1, 5HT, intracellular Mg,
      plasma calcium p(Ca), PTH, (25(OH)D) and thyroid functionality. Some typical
      symptoms were investigated. RESULTS: Eighty-one patients resulted positive for
      spamophilia (FM+SP), while 233 resulted negative for spasmophilia (FM). The mean
      TP number resulted higher in the FM group (15.33+/-3.88) with respect to FM+SP
      (12.88+/-6.17, p=0.016), while FIQ and HAQ did not differ between the two studied
      groups. FM patients exhibited a higher frequency of psychiatric disorders with
      respect to FM+SP patients (72% FM vs. 49% FM+SP, p<0.01). In particular the
      frequency of depression was 65.5% FM vs. 35% FM+SP (p<0.01). CONCLUSIONS: The
      presence of spasmophilia seems to influence psychiatric comorbidity which was
      less prevalent in FM+SP patients. FM is indeed characterised by an abnormal
      sensory processing of pain that seems to result from a combination of
      interactions between neurotransmitters, stress, hormones and the nervous system;
      spasmophilia would seem to be more linked to a dysfunction at the neuromuscular
      level.

PMID- 21176429
TI  - Assessing sleep in fibromyalgia: investigation of an alternative scoring method
      for the Jenkins Sleep Scale based on data from randomized controlled studies.
AB  - OBJECTIVES: To investigate the validity of a rescored version of the Jenkins
      Sleep Scale (JSS) to assess the extent of possible bias of a 4-week recall period
      in assessing sleep in patients with fibromyalgia. METHODS: A rescoring algorithm
      of the JSS was developed. The psychometric properties of the rescored JSS were
      examined using blinded, observed data from a Phase 2 trial (n=195) in subjects
      with fibromyalgia. In addition, data from two Phase 3, randomised, controlled
      trials (n=1,121) in subjects with fibromyalgia were used to further validate the
      rescored JSS by conducting correlation analyses with other assessments expected
      to correlate with sleep. These included fatigue and tiredness items from the
      Fibromyalgia Impact Questionnaire (FIQ), the Functional Outcomes of Sleep
      Questionnaire (FOSQ), and the Short Form-36 (SF-36TM) Vitality scale. RESULTS:
      Construct validity of the rescored JSS was found to be acceptable, with an
      internal consistency reliability of alpha=0.70. Test-retest reliability on stable
      subjects, defined using the FIQ total score, was also acceptable (ICC=0.70).
      Moderate to high correlations (Pearson r>0.66) were found with two FIQ items,
      addressing fatigue and non-restorative sleep, and the SF-36TM Vitality scale;
      correlations with the original JSS were similar. Both JSS versions were found to
      be responsive (p<0.0001), and the rescored version accounted for 90% of the
      variance captured in the original version. CONCLUSIONS: These results showed the
      rescored JSS performed similarly to the original scale, suggesting the original
      scale's 4-week recall period did not introduce substantial bias in capturing the
      experience of fibromyalgia-related sleep disturbances.

PMID- 21176430
TI  - Pharmacological treatment of fibromyalgia.
AB  - Fibromyalgia (FM) is a common syndrome characterised by widespread pain and at
      least 11/18 painful tender points that requires multimodal pharmacological
      treatment also combined with non-pharmacological therapy. Various drugs currently
      are available to control the complex and different symptoms reported by patients.
      Only three drugs (duloxetine, milnacipram, pregabalin) are approved by the
      American Food and Drug Administration (FDA) and none by the European Medicines
      Agency (EMEA), consequently, off-label use is habitual in Europe. Most of the
      drugs improve only one or two symptoms; no drug capable of overall symptom
      control is yet available. Furthermore, different classes of drugs with different
      mechanisms of action are used off-label, including tricyclic antidepressants
      (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine
      reuptake inhibitors (SNRIs), opioids, non-steroidal anti-inflammatory drugs
      (NSAIDs), growth hormone, corticosteroids and sedative hypnotics. As no single
      drug fully manages FM symptoms, multicomponent therapy should be used from the
      beginning. Various pharmacological treatments have been used to treat FM with
      inconclusive results, and gradually increasing low doses is suggested in order to
      maximise efficacy. The best treatment should be individualised and combined with
      patient education and non-pharmacological therapy.

PMID- 21176431
TI  - Which kind of exercise is best in fibromyalgia therapeutic programmes? A
      practical review.
AB  - All of the specialists who deal in some way with fibromyalgia (FM) broadly agree
      that physical reconditioning programmes are useful, but it is not yet clear what
      type of physical activity is the most appropriate for different subsets of
      patients. The aim of this review was to examine the randomised controlled trials
      (RCTs) published between 1985 and August 2010 whose outcome measures indicate the
      effectiveness of different types of physical exercise (PE) on the main health
      domains affected by FM: pain, and physical and mental function. Studies that
      simultaneously used different types of PE or multimodal treatment strategies were
      excluded from the analysis, as were those in which the primary and secondary
      endpoints prevented any assessment of treatment efficacy in all three health
      domains. Twenty-seven studies were selected: 15 considered land-based physical
      aerobic exercise (PAE); seven exercises in water; and five muscle strengthening
      exercise (MSE). There was substantial uniformity in assessing the effectiveness
      of land- or water-based PAE and MSE in improving aerobic physical fitness (PF)
      and functional state. Water-based PAE offers some advantages over similarly
      intense land-based PAE in reducing spontaneous pain and improving depressive
      symptoms, but the data are insufficient to establish its overall superiority.
      Regardless of method, the latest findings concerning the neurophysiology of
      nociception indicate the fundamental importance of assigning workloads that do
      not exacerbate post-exercise pain.

PMID- 21176432
TI  - Exploring the abyss of fibromyalgia biomarkers.
AB  - Many researchers are studying fibromyalgia to identify objective, measurable
      biomarkers that may identify the patients, for the purpose of diagnosis or to
      measure the disease activity. The recent literature proposes instrumental or
      molecular biomarkers, but several of these are only useful for research purposes.
      Concentrated efforts to systematically evaluate additional objective measures in
      research trials will be vital for the ongoing progress in outcome research and
      translation into clinical practice. The aim of this review is a guided tour of
      the specific literature.

PMID- 21176433
TI  - Aspartame-induced fibromyalgia, an unusual but curable cause of chronic pain.
AB  - We report for the first time an unusual musculoskeletal adverse effect of
      aspartame in two patients. A 50-year-old woman had been suffering from widespread
      pain and fatigue for more than 10 years leading to the diagnosis of fibromyalgia.
      During a vacation in a foreign country, she did not suffer from painful symptoms
      since she had forgotten to take her aspartame. All of the symptoms reappeared in
      the days following her return when she reintroduced aspartame into her daily
      diet. Thus, aspartame was definitively excluded from her diet, resulting in a
      complete regression of the fibromyalgia symptoms. A 43-year-old man consulted for
      a 3-year history of bilateral forearm, wrist, and hand and cervical pain with
      various unsuccessful treatments. A detailed questioning allowed to find out that
      he had been taking aspartame for three years. The removal of aspartame was
      followed by a complete regression of pain, without recurrence. We believe that
      these patients' chronic pain was due to the ingestion of aspartame, a potent
      flavouring agent, widely used in food as a calorie-saver. The benefit/ risk ratio
      of considering the diagnosis of aspartame-induced chronic pain is obvious: the
      potential benefit is to cure a disabling chronic disease, to spare numerous
      laboratory and imaging investigations, and to avoid potentially harmful
      therapies; the potential risk is to temporarily change the patient's diet. Thus,
      practitioners should ask patients suffering from fibromyalgia about their intake
      of aspartame. In some cases, this simple question might lead to the resolution of
      a disabling chronic disease.

PMID- 21176435
TI  - A painful train of events: the rebirth of railway spine.

PMID- 21176436
TI  - The relevance of cross-diffusion in the formation of Turing patterns.
AB  - Over the years, the Rosenzweig-MacArthur (RM) model has been used to study simple
      prey-predator systems. It has been observed, however, that the RM model cannot
      sustain Turing patterns when using a diagonal diffusion tensor. As a result,
      researchers have introduced changes to the RM model that induce stable Turing
      patterns. In most cases, the changes have been made to the so-called response
      function, changing the interspecies interaction, or by adding an intraspecies
      interaction to the model. In this communication, we study the original RM model
      but we include cross-diffusion, which considers off diagonal elements in the
      diffusion tensor. Although cross-diffusion is well characterized in
      multicomponent solutions, including electrolytes, it has an apparent
      counterintuitive meaning in predator-prey systems. We observe, however, that in
      plant and fish systems, the lack of predator mobility is compensated by their
      ability to camouflage and attract their prey, which yields a negative cross
      diffusion coefficient. We show that negative cross-diffusion is enough to trigger
      stable Turing patterns in the RM model.

PMID- 21176437
TI  - Biotic patterns of heart rate variation in depressed and psychotic subjects.
AB  - This article presents novel quantitative methods to study R to R interval (RRI)
      series that identify their characteristic pattern of organization, Bios, and
      their variation in psychiatric illness. In this study twenty-four hour series of
      RRI were extracted from Holter recordings of healthy subjects (N = 74) and small
      groups of patients with affective depression or psychosis. These data were
      analyzed with recurrence and statistical methods. In all subjects, RRI series
      showed complexes (clusters of recurrences), such as those observed with
      mathematically-generated biotic series but not in chaotic or random series. RRI
      series from healthy persons showed diversification (increase in variance with the
      duration of the series analyzed), novelty (less recurrence isometry than copies
      randomized by shuffling), causal order (more consecutive isometry than shuffled
      copies), and asymmetric statistical distribution. These imprints of creative
      processes are characteristic of mathematical Bios, and are absent in chaos. Bios
      can be distinguished from random walk series by the nonrandom pattern of the
      series of differences between heartbeats, as well as by measures of consecutive
      isometry and of partial autocorrelation. These defining characteristics of Bios
      are significant signs of health. In comparison with healthy controls, psychiatric
      patient groups showed more isometry and more consecutive isometry than healthy
      subjects. Psychiatric patients also showed no diversification. This study
      highlights the process that produces heart rate variation as being non-stationary
      and creative (bios, not equilibrium or chaos) and causal (not stochastically
      generated by the coexistence of multiple factors). These results thus are
      significant regarding psychiatric health.

PMID- 21176438
TI  - Theory of positive disintegration as a model of adolescent development.
AB  - This article introduces a conceptual model of the adolescent development based on
      the theory of positive disintegration combined with theory of self-organization.
      Dabrowski's theory of positive disintegration, which was created almost a half
      century ago, still attracts psychologists' and educators' attention, and is
      extensively applied into studies of gifted and talented people. The positive
      disintegration is the mental development described by the process of transition
      from lower to higher levels of mental life and stimulated by tension, inner
      conflict, and anxiety. This process can be modeled by a sequence of patterns of
      organization (attractors) as a developmental potential (a control parameter)
      changes. Three levels of disintegration (unilevel disintegration, spontaneous
      multilevel disintegration, and organized multilevel disintegration) are analyzed
      in detail and it is proposed that they represent behaviour of early, middle and
      late periods of adolescence. In the discussion, recent research on the adolescent
      brain development is included.

PMID- 21176439
TI  - Social-support moderated stress: a nonlinear dynamical model and the stress
      buffering hypothesis.
AB  - Health psychology has studied the cross-sectional, stationary relationships
      linking stress, social support, and health. Levels of stress-related illness are
      generally modeled by including a nonlinear multiplicative or 'buffering' effect,
      corresponding to the interaction of stressor levels with social support from
      family and friends. The motivation of the present research is to extend an
      iterative, dynamic model of this well-investigated psychological process using a
      dynamical systems model expressed as a set of continuous, nonlinear differential
      equations similar to those of the 'Oregonator,' a model of a nonlinear dynamic
      chemical system. This model of the behavior of an individual is amenable to
      numerical investigation of its stationary-state stability properties, temporal
      evolution, and cause-effect relationships. The continuous variables in this new
      approach refer to varying states of an individual; they are Perceived stress (X),
      Symptoms (Y), and Social support (Z). It is expected that poor health in this
      model, represented by Symptoms (Y), is directly related to Perceived stress, as
      well as being tied in more complicated ways to Social support. A number of such
      models may be envisioned, some including a multiplicative, 'buffering' (- X x Z)
      effect of social support dependent on stress levels. We explore the behavior of
      this model over ranges of parameter values and initial conditions and relate
      these results to how an individual reacts to environmental challenges at various
      levels of stressors and social-support recruitment. Data generated by the model
      are in turn analyzed with a traditional cross-sectional statistical technique.
      Similarities and differences between chemical and psychological systems are
      discussed.

PMID- 21176440
TI  - Leadership emergence in engineering design teams.
AB  - Leaders emerge from leaderless groups as part of a more complex emerging social
      structure. Several studies have shown that the emerging structure is aptly
      described by a swallowtail catastrophe model where the control parameters differ
      depending on whether creative problem solving, production, coordination
      intensive, or emergency management groups are involved. The present study
      explored creative problem solving further where the participants were engaged in
      real-world tasks extending over several months rather than short laboratory
      tasks. Participants were engineering students who were organized into groups of
      to people who designed, built, and tested a prototype product that would solve a
      real-world problem. At the th week of work they completed a questionnaire
      indicating who was most like the leader of their group, second most like the
      leader, along with other questions about individuals' contributions to the group
      process. Results showed that the swallowtail model (R = .) exhibited a strong
      advantage over the linear alternative model (R = .) for predicting leadership
      emergence. The three control variables were control of the task, creative
      contributions to the group's work, and facilitating the creative contributions of
      others.

PMID- 21176441
TI  - Numerical exploration of Kaldorian interregional macrodynamics: stability and the
      trade threshold for business cycles under fixed exchange rates.
AB  - The stability of equilibrium and the possibility of generation of business cycles
      in a discrete interregional Kaldorian macrodynamic model with fixed exchange
      rates are explored using numerical methods. One of the aims is to illustrate the
      feasibility and effectiveness of the numerical approach for dynamical systems of
      moderately high dimensionality and several parameters. The model considered is
      five-dimensional with four parameters, the speeds of adjustment of the goods
      markets and the degrees of economic interactions between the regions through
      trade and capital movement. Using a grid search method for the determination of
      the region of stability of equilibrium in two-dimensional parameter subspaces,
      and coefficient criteria for the flip bifurcation - and Hopf bifurcation - curve,
      we determine the stability region in several parameter ranges and identify Hopf
      bifurcation curves when they exist. It is found that interregional cycles emerge
      only for sufficient interregional trade. The relevant threshold is predicted by
      the model at 14 - 16 % of trade transactions. By contrast, no minimum level of
      capital mobility exists in a global sense as a requirement for the emergence of
      interregional cycles; the main conclusion being, therefore, that cycles may occur
      for very low levels of capital mobility if trade is sufficient. Examples of
      bifurcation and Lyapunov exponent diagrams illustrating the occurrence of cycles
      or period doubling, and examples of the development of the occurring cycles, are
      given. Both supercritical and subcritical bifurcations are found to occur, the
      latter type indicating coexistence of a point and a cyclical attractor.

PMID- 21176442
TI  - The art and science of foam bubbles.
AB  - Art and science become inevitably intertwined in our appreciation of nature's
      forms. This concept is demonstrated by the creative team responsible for the
      cover images of Nonlinear Dynamics, Psychology, and Life Sciences. Denis Weaire,
      Stefan Hutzler, Wiebke Drenckhan form a leading international collaboration with
      photographers Tim Durham and Michael Boran that explores the physics of bubble
      patterns. The images they generate capture and manipulate the striking aesthetic
      impact of foam bubbles. Furthermore, the foams exhibit a balance between
      simplicity and intricacy that symbolizes many of the complex systems that
      permeate nature and society.

PMID- 21176443
TI  - [Experimental study on molecular mechanism of nm23-H1 gene transfection reversing
      the malignant phenotype of human high-metastatic large cell lung cancer cell
      line].
AB  - BACKGROUND: nm23-H1 gene is a well-known tumor metastasis suppression gene. Our
      previous study has found that transfection of wild type nm23-H1 gene can
      significantly downregulate the ERK1/2 activity of human high-metastatic large
      cell lung cancer cell line L9981. The aim of this study is to investigate the
      influence of nm23-H1 and exogenous ERK1/2 pathway inhibitor U0126 on the
      extracellular signal-regulated kinase (ERK1/2) of human high-metastatic large
      cell lung cancer cell line L9981 and its malignant biological behaviors. METHODS:
      The expressive levels of total-ERK1/2, dually phosphorylated ERK1/2 and ERK1/2
      relative activity of the human high-metastatic large cell lung cancer cell lines,
      L9981 (parent cell line with nm23-H1 gene hetero-deletion), L9981-nm23-H1
      (transfected with nm23-H1 gene ) and L9981-PLXSN (transfected with vector) were
      detected by Western blot and immunoprecipitation technique after treating with
      U0126 (40MUmol/L for 20 minutes). The in vitro proliferative and invasive
      abilities among the above three lung cancer cell lines were determined by MTT and
      improved Boyden chamber methods. RESULTS: The phosphorylated ERK1/2 expression
      level and relative activity in L9981-nm23-H1 lung cancer cell line were
      remarkably lower than those in L9981 and L9981-PLXSN lung cancer cell lines after
      being treated with U0126 (P < 0.01), but there was no significant difference
      between L9981 and L9981-PLXSN lung cancer cell lines. No significant difference
      of total ERK1/2 expression level was observed among the three lung cancer cell
      lines (P > 0.05) after being treated with U0126. The in vitro proliferation and
      invasion of L9981-nm-23H1 lung cancer cell line were remarkably lower than those
      of L9981 and L9981-PLXSN lung cancer cell lines (P < 0.01 ), but no significant
      difference was found between L9981 and L9981-PLXSN lung cancer cell lines (P >
      0.05 ); U0126 could significantly down-regulate the in vitro proliferation and
      invasion of L9981 lung cancer cell line (P < 0.01). CONCLUSIONS: Blocking the
      activity of ERK1/2 in L9981 lung cancer cell line and transfecting the nm23-H1
      gene into the L9981 lung cancer cell line may produce similar cell biological
      behavior changes, namely the significant reduction of in vitro proliferation and
      invasion of L9981 lung cancer cell line. These results indicate that the
      molecular mechanism which nm23-H1 gene reverses invasion and proliferation of the
      human high-metastatic large cell lung cancer cell line may be related to its
      effects of down-regulating the activity of the key kinase ERK1/2 of Ras-to-MAPK
      signal transduction pathway.

PMID- 21176444
TI  - [c-fos antisense oligodeoxynucleotide reduces VIP-induced upregulation of VEGF
      expression in small cell lung cancer cells].
AB  - BACKGROUND: It has been known that vasoactive intestinal peptide (VIP) has the
      effect of promoting the growth of some malignant tumors, but its mechanism is not
      clear. The aim of this study is to use c-fos antisense oligodeoxynucleotide (ASO)
      to block c-fos expression and to explore whether c-fos can directly regulate VIP
      induced VEGF expression in small cell lung cancer (SCLC) cells. METHODS:
      Expression levels of c-fos and VEGF genes were detected in SCLC cell line H446
      treated with VIP by RT-PCR. After c-fos ASO was added to the H446 cells, the
      change of VEGF mRNA expression level was analyzed. RESULTS: Administration of VIP
      resulted in increased expression of c-fos and VEGF mRNA in the H446 cells. The
      expression of c-fos mRNA reached the peak level at 2h and 4h after VIP treatment,
      which was significantly higher than that at 0h (P < 0.01). Whereas, the highest
      expression level of VEGF mRNA was observed at 8h and 16h after VIP treatment,
      which was significantly higher than that at 0h (P < 0.01). c-fos ASO
      significantly reversed VIP-induced upregulation of VEGF mRNA expression (P <
      0.01) CONCLUSIONS: VIP can increase the expression and secretion of VEGF in lung
      cancer cells by activating the transcription factor c-fos, then promote the
      angiogenesis of lung cancer and thus play an important role in the pathogenesis
      of lung cancer.

PMID- 21176445
TI  - [The relationship between HVRII mutation of mitochondrial DNA and squamous cell
      carcinoma of the lung].
AB  - BACKGROUND: Mitochondrial DNA (mtDNA) is the only hereditary substance besides
      nucleus, which is composed of a code region and a non-code D-loop region. The aim
      of this study is to investigate the hypervariable region II (HVRII) mutation of
      mtDNA in peripheral blood leucocyte, pericancerous tissues and cancer tissues of
      lung squamous cell carcinoma patients, and to explore its significance. METHODS:
      White blood cells, pericancerous tissues and cancer tissues were obtained from 15
      cases of lung squamous cell carcinoma patients and mtDNA were extracted by one
      step method. HVRII fragments were amplified by PCR. Mutations were determined by
      DNA sequencing and the mutations of HVRII were analysed. RESULTS: In 15 lung
      squamous cell carcinoma patients, 14 patients showed mutation in HVRII(93.33%),
      88 mutations were found totally. Eighty-seven mutations located in H-strand
      origin region, especially in the conserved sequence blocks and the mtTF1, 2
      binding site (TFX and TFY). CONCLUSIONS: The results suggest that the mutation
      frequency of HVRII in cancer tissues of lung squamous cell carcinoma patients is
      very high and it might play an important role in carcinogenesis of the lung.

PMID- 21176446
TI  - [Expression of FHIT gene in precancerous lesions and primary lung cancer
      tissues].
AB  - BACKGROUND: Fragile histidine triad (FHIT) gene, a candidate tumor suppressor
      gene, is recently identified at chromosome 3p14.2, spanning the FRA3B common
      fragile site. Abnormalities in expression of FHIT gene have been reported in a
      variety of human tumours including lung cancer. The aim of this study is to
      investigate the expression of FHIT gene in precancerous lesions and primary lung
      cancer and to analyze the role of FHIT gene in lung tumorigenesis. METHODS: FHIT
      protein expression was detected in 298 cases of formalin fixed paraffin-embedded
      human samples by immunohistochemistry, including 51 precancerous lesions, 161
      lung cancer samples, 30 normal lung tissue samples, 23 pulmonary benign lesion
      tissues and 33 metastatic lymph nodes. RESULTS: All the normal lung tissues and
      pulmonary benign lesions showed positive FHIT protein expression, while the
      negative rate of FHIT protein expression in precancerous lesions, lung cancer
      tissues and metastatic lymph nodes was 54.9%, 59.0% and 78.8% respectively.
      Negative rate of FHIT protein in metastatic lymph nodes, lung cancer tissues and
      precancerous lesions was significantly higher than that in normal lung tissues
      and pulmonary benign lesions (P < 0.001). The expression of FHIT gene was closely
      related to histological classification, cell differentiation, pTNM stages and
      lymph node metastasis in lung cancer (P < 0.05). A marked reduction of FHIT
      protein expression was observed in patients with smoking history than that in
      patients without smoking history (P < 0.01). Furthermore, FHIT protein expression
      level in lung cancer was associated with survival of patients (P < 0.01).
      CONCLUSIONS: These results suggest that FHIT protein expression may occur at
      early stage of lung carcinogenesis and be associated with the oncogenesis and
      progression of cancer. The correlation between cigarette smoking and FHIT
      expression suggests a role of FHIT in the initiation of smoking-related lung
      tumorigenesis.

PMID- 21176447
TI  - [Expression and clinicopathologic significance of OPN, CD44v6 and MMP-2 in
      squamous cell carcinoma and adenocarcinoma of the lung].
AB  - BACKGROUND: There are a lot of studies on relationship of surface adhesion
      molecule (CD44) and matrix metalloproteinase (MMP) with tumors in recent years,
      however study on osteopontin (OPN) is still few. The aim of this study is to
      investigate the levels of OPN, CD44v6 and MMP-2 in squamous cell carcinoma and
      adenocarcinoma of the lung, and to clearly understand their roles in growth,
      invasion and metastasis of squamous cell carcinoma and adenocarcinoma. METHODS:
      OPN, CD44v6 and MMP-2 were detected in 69 patients with squamous cell carcinoma
      and adenocarcinoma by immunohistochemical method. RESULTS: The expression rate of
      OPN, CD44v6 and MMP-2 was significantly related to histological classification,
      TNM stages and lymph node metastasis (P < 0.05), but not to cell differentiation
      (P > 0.05). There was a positive correlation between OPN and CD44v6 expression (P
      < 0.001), as well as between OPN and MMP-2 expression (P < 0.001). There was no
      correlation between CD44v6 and MMP-2 expression. CONCLUSIONS: OPN, CD44v6 and MMP
      2 expression is related to the histology, TNM stages and lymph node metastasis of
      lung cancer. They might be used as clinical indicators to predict the progress
      and metastatic potential for squamous cell carcinoma and adenocarcinoma of the
      lung.

PMID- 21176448
TI  - [mRNA expression of MAGE genes in benign and malignant pleural effusion].
AB  - BACKGROUND: Melanoma antigen genes (MAGE) are tumor specific genes. The aim of
      this study is to explore the feasibility of MAGE genes detection as a diagnostic
      method for malignant pleural effusion. METHODS: The expression of MAGE-1, -2, -3
      and -4 mRNA was detected in 18 benign and 22 malignant pleural effusion samples
      by RT-PCR. RESULTS: No MAGE gene expressed in the 18 cases of benign pleural
      effusion. Out of the 22 cases of malignant pleural effusion, 8 cases were
      positive by cytological examination, who all showed positive expression of MAGA
      genes; in the other 14 patients who were positive by pleural biopsy but negative
      by cytological examination, 11 cases showed positive expression of MAGE genes in
      both the pleural effusion and pleura samples, while the other 3 cases showed
      negative MAGE expression in both the pleural effusion and pleura samples.
      CONCLUSIONS: Detection of MAGE genes in pleural effusion may be an effective
      method in the differential diagnosis of benign and malignant pleural effusion.

PMID- 21176449
TI  - [Study on relationship between blood supply from pulmonary artery and
      pathological characteristics of patients with primary bronchogenic carcinoma].
AB  - BACKGROUND: At present, it has been known that the bronchogenic artery
      participates in the blood supply of primary bronchogenic carcinoma, but there is
      controversy about the blood supply from pulmonary artery in primary bronchogenic
      carcinoma. The aim of this study is to assess the relationship between the blood
      supply from pulmonary artery and pathological characteristis of patients with
      primary bronchogenic carcinoma. METHODS: The pulmonary arteries in 43 surgical
      samples of bronchogenic carcinoma were marked, then the iopromide was used to
      selective pulmonary arteriography in digital subtraction angiography (DSA). The
      relationship between tumor with blood supply from pulmonary artery and the
      pathologic characteristics was observed. RESULTS: There were 34 samples with
      blood supply from pulmonary artery ( 79.07%) , and 9 samples without blood supply
      from pulmonary artery (20.93%). The development rate of peripheral lung cancer
      (100.00%) was significantly higher than that of central lung cancer (64.00%) (P <
      0.01) . The development rate of squamous cell carcinoma (91.30%) was remarkably
      higher than that of adenocarcinoma (61.11%) (P < 0.05). The development rate of
      poorly differentiated lung cancer (95.00%) was remarkably higher than that of
      well and moderately differentiated lung cancer (65.22%) (P < 0.05). There was a
      positive relationship between the tumor size and the development rate (P < 0.05).
      CONCLUSIONS: In primary bronchogenic carcinoma, the pulmonary artery blood supply
      exists in most of tumors. There is relationship between the blood supply from
      pulmonary artery and general type, histopathology, cell differentiation and tumor
      size of lung cancer. The blood supply from pulmonary artery doesn't relate to
      tumor stage.

PMID- 21176450
TI  - [Expression and significance of CEA and CA153 in pleural fluid of patients with
      lung cancer].
AB  - BACKGROUND: Finding the cancer cells in pleural fluid of patients with lung can
      cer by conventional cytology is always a difficult point. In order to enhance the
      diagnostic rate of pleural fluid with lung cancer, carcinoembryonic antigen (CEA)
      and cancer antigen 153 (CA153) were detected in serum and pleural fluid, and
      their diagnostic values on lung cancer were analyzed. METHODS: Quantities of CEA
      and CA153 were detected by chemiluminescence in both serum and pleural fluid of
      patients with lung cancer (74 cases) and without lung cancer (34 cases). RESULTS:
      The levels of CEA and CA153 in pleural fluid of patients with lung cancer were
      significantly higher than those without lung cancer (P < 0.01). The levels of CEA
      and CA153 in serum of patients with lung cancer were distinctly higher than those
      without lung cancer (P < 0.01). The levels of CEA and CA153 in pleural fluid were
      obviously higher than those in serum (P < 0.01). The optimal diagnostic assay of
      lung cancer was CEA+CA153 combination: sensitivity and specificity were 85.1% and
      97.1% respectively. CONCLUSIONS: It could be of important clinical significance
      for diagnosing lung cancer by assaying CEA and CA153 in pleural fluid of patients
      with lung cancer.

PMID- 21176451
TI  - [A primary study of immunotherapy with carcinoembryonic antigen peptide-pulsed,
      autologous human cultured dendritic cells in patients with advanced non-small
      cell lung cancer].
AB  - BACKGROUND: Dendritic cell (DC)-based immunotherapy is a new approach and
      effective for some malignant tumors. The aim of this study is to observe the
      efficacy and toxicity of immunotherapy with carcinoembryonic antigen (CEA)
      peptide-pulsed DCs in patients with refractory advanced lung cancer. METHODS:
      Lung cancer patients with high CEA expression were enrolled into this project.
      Autologous DCs were generated from patients' plastic-adherent peripheral blood
      mononuclear cells and loaded with CEA 5 days later. Cytokine-induced killer cells
      (CIK) were cultured from non-adherent peripheral blood mononuclear cells. DCs and
      CIK were transfused to patients. Responses and toxicities were observed. RESULTS:
      A total of 22 patients with lung cancer received DCs immunotherapy. DCs doses
      were 2.5*106-9.6*107 (5.03*106). CIK doses were 3.4*108-46*108. CD3, CD8, NK and
      IFN-gamma levels obviously increased after treatment (P < 0.05). The 1-year
      survival rate was 68.2% (15/22). Main toxicities were fever and rash.
      CONCLUSIONS: DCs-based immunotherapy is feasible and safe to patients with lung
      cancer.

PMID- 21176452
TI  - [A preliminary study on image guided hypofractionated radiotherapy for pulmonary
      tumor].
AB  - BACKGROUND: Image guided radiotherapy (IGRT) is a new precise radiotherapy
      applied in clinic. The aim of this study is to evaluate the impact of using
      active breath control (ABC) and stereotactic body frame on reducing the
      positioning error and increasing treatment precision during radiotherapy for
      pulmonary cancer. METHODS: Seven patients with pulmonary recurrences or
      metastasis after prior treatment were enrolled. A total number of 13 tumor
      targets received irradiation, with a fraction dose of 7Gy treated every other day
      to a total of 7 fractions. X-ray beam volume CT was done at every fraction for
      correction of positioning error at 3 dimensions. RESULTS: The errors between pre
      treatment positioning and treatment planning at left-right, anterior-posterior
      and cephalic-caudal directions were 0.30cm+/-0.14cm, 0.22cm+/-0.15cm and 0.28cm
      +/-0.21cm, respectively. The positioning error was reduced after correction by
      volume CT and after treatment but the errors between pre-correction, post
      correction and post-treatment had no statistical significance at all 3
      directions. Eight targets had complete response, 4 targets had partial response,
      and 1 had no change. CONCLUSIONS: Image guided hypofractionation radiotherapy
      with ABC and stereotactic body frame has the advantage of increasing radiation
      dose and reducing overall treatment time and radiation toxicity.

PMID- 21176453
TI  - [Application of cardiopulmonary bypass during extended resection of locally
      advanced lung cancer].
AB  - BACKGROUND: Locally advanced lung cancer includes IIIA and IIIB lung cancer that
      tumors are localized within the chest and with no clinic and pathologic distal
      metastasis. In this study the results of extended resection of a portion of heart
      or great vessels with cardiopulmonary bypass was summarized in the treatment of
      locally advanced lung cancer. METHODS: Lobectomy or pneumonectomy combined with
      extended partial excision of the heart or great vessels were carried out in 10
      patients with locally advanced lung cancer. The operations included aortic
      resection and reconstruction with left heart bypass in 2 cases, extended
      resection of left atrium with normal cardiopulmonary bypass in 5 cases, and
      resection and reconstruction of superior vena cava in 3 cases respectively.
      RESULTS: The patients had no operative complication except for one haemothorax,
      which was controlled by re-exploration. One patient died of brain metastasis 6
      months after operation and another one died of multiple metastasis 26 months
      after operation. The others were alive. CONCLUSIONS: CPB is a safe and effective
      anesthetic procedure during extended resection of locally advanced lung cancer
      although it is controversial for aggravating operative trauma, complex technique
      and higher cost.

PMID- 21176454
TI  - [Trachea,bronchus,blood vessel and left atrium plasty in the treatment of lung
      cancer].
AB  - BACKGROUND: The trachea, bronchus, blood vessel and left atrium plasty can
      maximumly remove tumor tissus and preserve the functional pulmonary tissues so as
      to improve patients' quality of life and prolong their survival. METHODS: From
      January 1990 to August 2004, 125 patients with lung cancer underwent trachea,
      bronchus, bloood vessel and left atrium plasty. RESULTS: There were 116 patients
      who underwent bronchoplasty, in which angioplasty was performed concurrently in
      26 cases. And reconstruction of superior vena cava was performed in 3 patients,
      and left atrium plasty in 6 patients. Three patients died after operation.
      CONCLUSIONS: Trachea, bronchus, blood vessel and left atrium plasty may be a
      promising direction in thoracic surgery.

PMID- 21176455
TI  - [Survival after pulmonary metastasectomy: experience in 26 patients].
AB  - BACKGROUND: Surgical resection becomes standard treatment for pulmonary
      metastatic tumor with operative indication. The aim of this study is to analyze
      the indication and surgical efficacy of pulmonary metastasectomy. METHODS: From
      November 1991 to May 2003, a total of 26 patients with pulmonary metastatic
      tumors were treated surgically in our hospital, 12 cases were males and 14
      females, with an average age of 50 years old. The metastatic tumors came from
      different organs and tissues, 5 cases accompanied by metastatic tumors of liver
      or brain. RESULTS: Four cases underwent pneumonectomy, 8 lobectomy, and 14 wedge
      resection (in which 8 cases underwent mildly invasive operation using video
      assisted thoracic surgery). No operative death occurred. 5-year survival rate was
      27.3% (3/11), 2-year survival rate 42.9% (9/21) and 1-year survival rate 69.2%
      (18/26). CONCLUSIONS: Pulmonary metastasectomy is recommended in pulmonary
      metastases with operative indication, and is still effective in cases accompanied
      by resectable metastatic tumors of liver or brain. Mildly invasive operation
      using video-assisted thoracic surgery might be chosen for some cases with single
      metastatic locus.

PMID- 21176456
TI  - [Diagnostic value of nuclide bone imaging for bone metastasis from lung cancer
      and clinic analysis].
AB  - BACKGROUND: Bone metastasis is very common in lung cancer patients. Metastasis to
      spine can lead to paralysis and fracture, deteriorate the quality of patient's
      life. The objective of this study is to investigate the diagnostic values of bone
      scanning (NBS), MRI, CT and X-ray examination to discover bone meastasis of lung
      cancer, and the therapy of bone metastasis and the prognostic factors. METHODS:
      About 561 consecutive NSCLC cases were analyzed with NBS and compared with other
      radiological examinations (MRI, CT and X-ray). RESULTS: Out of the 455 positive
      patients by NBS, 300 cases were confirmed to be with bone metastases by dynamic
      follow-up, MRI, CT and X-ray, and 5 cases were false negative.The sensitivity and
      specificity of NBS was 98.36% and 39.45% respectively. The accuracy of NBS was
      71.48%. Among the 305 patients with bone metastases, 23 patients had no records,
      138 patients had bone pain, the incidence of asymptomatic bone metastasis was
      47.21%. Multivariables analysis showed that asymptomatic bone metastasis, flat
      bone metastases, therapy with disodium pamidronate were significantly good
      prognostic factors, respectively (P < 0.05). CONCLUSIONS: A whole body NBS
      examination is preferred for the staging of NSCLC. NBS is necessary for patients
      with NSCLC. In order to exclude the possible false positive or false negative
      diagnosis by NBS, CT or MRI could be selected according to the sites of lesions.

PMID- 21176457
TI  - Phase I/II study of gemcitabine and oxaliplatin chemotherapy in combination with
      concurrent 3-D conformal radiotherapy for locally advanced non-small cell lung
      cancer.
AB  - BACKGROUND: Recent studies have showed that combination of chemotherapy and
      radiotherapy might result in better outcome for locally advanced non-small cell
      lung cancer (NSCLC). The aim of this study is to determine the maximal tolerance
      dose (MTD) and efficacy of full-dose gemcitabine and oxaliplatin when given
      concurrently with 3-dimentional radiation therapy (3D-RT) for locally advanced
      NSCLC. METHODS: Oxaliplatin was administered at a fixed dose of 130mg/m2, and
      gemcitabine was administered at a starting dose of 800mg/m2 with an incremental
      dose gradient of 200mg/m2 for 3 dose levels. MTD was defined as the immediate
      dose level lower than the dose at which dose-limiting toxicity (DLT) occurred in
      more than one-third of the patients. The chemotherapy was administered at 3-week
      cycle. The RT was given as 3-D conformal manner at a single daily dose of 2Gy for
      5 days per week. RESULTS: Twenty-two patients were evaluable and distributed to
      three different dose levels: 6 at level 1, 8 at level 2 and 8 at level 3.
      Pulmonary toxicity, esophageal and hematologic toxicity were the main DLT. Grade
      III acute pulmonary toxicity occurred in one patient each at level 2 and level 3,
      both with V20 > 20%, and grade III esophagitis in two patients at level 3. The
      MTD of gemcitabine in this study was 1000mg/m2. The overall response rate was
      75.0% (9/12). The 1- and 2-year survival rate was 70.0% and 30.5% respectively.
      The median time to progression was 8.7 months (range 5-11.8 months). CONCLUSIONS:
      With reduced radiation volume, gemcitabine of 1000mg/m2 in combination with
      oxaliplatin of 130mg/m2 was effective and could be safely administered for NSCLC.

PMID- 21176458
TI  - [The role of the K+ channel in the inhibition of the human lung adenocarcinoma
      cell proliferation by rmhTNF].
AB  - BACKGROUND: With the development of patch clamp and molecular biology technique,
      and the application of them in the investigation of tumor cellular membrane ion
      channnel, the ion channel is becoming the hot spot of the tumor base research
      gradually. The aim of this study is to investigate the electrophysiological
      properties of human lung adenocarcinoma cell line A-549 and the role of K+
      channel in inhibition of cell proliferation by the recombinant mutant human tumor
      necrosis factor (rmhTNF). METHODS: Ionic currents were recorded using the whole
      cell patch clamp recording technique. The proliferation activity of A-549 cells
      was measured by MTT assay. The cell cycle and apoptosis rates of the carcinoma
      cells were measured by flow cytometric analysis (FCM). RESULTS: Whole-cell patch
      clamp recording revealed a voltage-gated K+ current in A-549 cells, which could
      be blocked by the K+ channel blocker, TEA and CsCl. The amplitude of K+ current
      was markedly diminished in all cells incubated with different concentration of
      rmhTNF (P < 0.01). Obvious inhibitive effect of rmhTNF on proliferation of the
      cells was found in vitro in a dose-dependent manner (P < 0.01), the maximal
      inhibitory rate was 38.68% when the concentration was 400U/mL. The rmhTNF
      inhibited the cell cycle shifting from G1 phase to S phase and promoted apoptosis
      as determined by FCM analysis. The proportion of G1 cells increased from 53.02%
      to 72.93%, and the apoptosis rate increased from 2.08% to 8.68%. The difference
      were significant between the control and the high concentration groups ( 200U/mL
      and 400U/mL) (P < 0.01). CONCLUSIONS: rmhTNF exerts its cytotoxic effects on A
      549 cells through inhibiting cell cycle shifting and inducing apoptosis. The K+
      channels on the A-549 cell membrane can be blocked by rmhTNF partly, and the
      effect of inhibiting proliferation and activating apoptosis on A-549 cells is a
      result of depression of the K+ channel.

PMID- 21176459
TI  - [An experimental study of telomerase reverse transcriptase (hTERT) DNAzyme on
      growth of A549/DDP cells].
AB  - BACKGROUND: Telomerase expresses in many cancers and may contribute to drug
      resistance. The aim of this study is to observe the effect of telomerase reverse
      transcriptase (hTERT) DNAzyme on growth of A549/DDP cells and to explore the
      possibility of telomerase as a new target in treatment of drug resistance for
      lung cancer. METHODS: An hTERT DNAzyme was composed. Telomerase activity was
      measured by telomeric repeat amplification protocol (TRAP) modified from Kim's
      method. MTT was used to show the influence of hTERT DNAzyme and cisplatin on
      A549/DDP cells. RESULTS: The telomerase activity of A549/DDP cells was down
      regulated by hTERT DNAzyme in a dose-dependent manner. The growth inhibition rate
      of A549/DDP cells was 32.9% by hTERT DNAzyme of 0.25MUmol/L, and 60.5% by hTERT
      DNAzyme combined with 3mg/L cisplatin. The CDI of hTERT DNAzyme and cisplatin was
      0.9. CONCLUSIONS: hTERT DNAzyme can inhibit the growth of A549/DDP cells and has
      a synergistic effect with cisplatin. It is suggested that telomerase may be a new
      target in treatment of drug-resistant lung cancer cells.

PMID- 21176460
TI  - [SNP767A/T of FUS2 gene and lung cancer risk in Chinese population].
AB  - BACKGROUND: FUS2 gene locating at 3p21.3 is considered a promising candidate
      tumor suppressor gene. The aim of this study is to examine the difference in FUS2
      767A/T polymorphism site between lung cancer patients and normal controls in
      Chinese population. METHODS: The genotype FUS2-767A/T was detected in 146 lung
      cancer patients and 113 normal controls by PCR-SSCP method. The relationship
      between lung cancer risk and difference in genotypes of FUS2 gene was analysed.
      RESULTS: FUS2-767A/T was significantly related to histological type (P=0.044),
      age of the patients with lung cancer (P=0.011) and vessel cancer embolus
      (P=0.031) in lung cancer group. There was no significant difference in
      distribution of FUS2 genotypes between lung cancer patients and normal controls
      (P=0.945). CONCLUSIONS: The results suggest that the FUS2-767A/T polymorphism may
      be a susceptibility factor for lung cancer among Chinese population.

PMID- 21176461
TI  - [Relationship between CYP1A1 and GSTM1 genetic polymorphisms and lung cancer
      susceptibility in population of Inner Mongolia].
AB  - BACKGROUND: Lung cancer is one of malignant tumors to hurt human health. It has
      been known that the development of lung cancer may be associated with genetic
      polymorphism of some lung cancer related genes. The aim of this study is to
      explore the susceptibility to lung cancer in relation to CYP1A1 and GSTM1 genetic
      polymorphisms in population of Inner Mongolia. METHODS: CYP1A1 and GSTM1 genetic
      polymorphisms were determined by PCR-RFLP in 163 lung cancer cases and healthy
      controls respectively. RESULTS: The frequencies of CYP1A1 variation genotype
      (vt/vt) and GSTM1(-) were 36.8% and 65.0% in lung cancer cases and 19.0% and
      48.9% in healthy controls respectively. Statistical tests showed significant
      difference in the frequencies between the two groups (Chi-Square =12.82,
      P=0.0001; Chi-Square = 9.78, P=0.002). The risk of lung cancer with CYP1A1
      variation genotype was significantly higher than those of controls (OR= 2.48, 95%
      CI=1.51-4.08). The individuals who carried with GSTM1-null genotype had a high
      risk of lung cancer (OR=2.03, 95% CI=1.30-3.17). Combined analysis of the
      polymorphisms showed that percentage of CYP1A1(vt/vt)/GSTM1(-) in lung cancer and
      control groups was 28.8% and 8.0% respectively (Chi-Square = 23.883, P=0.0001).
      The people who carried with CYP1A1(vt/vt)/GSTM1(-) had a high risk of lung cancer
      (OR=4.90, 95% CI=2.50-9.83). Pearson Chi-Square of sex differential showed there
      was no significance between the homozygous variation genotype of CYP1A1/GSTM1(-)
      and the other genotypes of CYP1A1/GSTM1(-) neither in lung cancer group (Chi
      Square=0.797, P=0.372) nor in control group (Chi-Square=0.670, P=0.761).
      Statistical tests showed that susceptibility to lung cancer was related to
      smoking (Chi-Square = 14.197, P=0.000), the risk of lung cancer in smoking
      individuals raised remarkably (OR=2.33, 95% CI=1.50-3.62). There may be a
      synergetic interaction between CYP1A1 variation genotype (vt/vt) and smoking on
      the elevated susceptibility to lung cancer (Chi-Square = 23.843, P=0.000), the
      smokers who carried with CYP1A1 (vt/vt) had a significantly higher risk of lung
      cancer (OR=4.44, 95% CI=2.40-8.32, Chi-Square = 23.843, P= 0.000). So did the
      GSTM1(-) and smoking on the elevated susceptibility to lung cancer, the
      significantly higher risk of lung cancer had also been found in those smokers who
      carried with GSTM1(-) (OR=7.32, 95% CI=3.39-15.50, Chi-Square = 36.708,P=0.000).
      CONCLUSIONS: The polymorphisms of CYP1A1 vt/vt and GSTM1(-) are the risk factors
      in lung cancer of Inner Mongolia. Smoking is also related to the susceptibility
      to lung cancer. There may be a synergetic interaction between CYP1A1 (vt/vt) and
      GSTM1(-) on the elevated susceptibility of lung cancer. So do the CYP1A1 (vt/vt),
      GSTM1(-) and smoking.

PMID- 21176462
TI  - [Expression and its significance of Pin1 and beta-catenin in squamous cell
      carcinoma and adenocarcinoma of the lung].
AB  - BACKGROUND: The conformation of a subset of phosphorylated serines or threonines
      preceding proline motifs is regulated by the prolyl isomerase Pin1. Pin1 plays a
      critical role in oncogenesis. The aim of this study is to explore the
      relationship between the expression of Pin1 and clinicopathological factors in
      squamous cell carcinoma and adenocarcinoma of the lung, and to analyze the
      correlation between Pin1 and beta-catenin. METHODS: The expression of Pin1 and
      beta-catenin proteins was detected in 69 lung cancer cases by immunohistochemical
      SP method, and in 30 fresh lung samples by Western blot. RESULTS:
      Immunohistochemically, the overexpression of Pin1 and beta-catenin in lung cancer
      was 78.3% (54/69) and 63.8% (44/69), respectively. The expression of Pin1 and
      beta-catenin was not related to age, sex, histological classification,
      differentiation, lymph node metastasis and pTNM stages. There was a positive
      correlation between overexpression of Pin1 and aberrant beta-catenin expression
      (P < 0.05). Western blot results showed that the expression of Pin1 and beta
      catenin in lung cancer tissues was significantly higher than that of
      paracancerous lung tissues (P < 0.05). CONCLUSIONS: Pin1 is overexpressed in
      squamous cell carcinoma and adenocarcinoma of the lung and may play a critical
      role in oncogenesis of lung cancer. Overexpression of Pin1 might contribute to
      the upregulation of beta-catenin and it may be one of the pathways for Pin1 to
      work.

PMID- 21176463
TI  - [RRM1 expression in tissue microarray and prognosis analysis in non-small cell
      lung cancer].
AB  - BACKGROUND: RRM1 may be a prognostic factor in non-small cell lung cancer
      (NSCLC). The aim of this study is to evaluate RRM1 expression and prognosis in
      NSCLC by the means of tissue microarray. METHODS: A total of 417 paraffin
      embedded specimens of NSCLC from Lung Cancer Study Center in Guangdong Provincial
      People's Hospital were collected and tissue microarray was constructed. RRM1
      expression was detected by SP method and its correlation with prognosis was
      evaluated. RESULTS: No statistic difference was found in RRM1 expression in
      different gender, age, tumor site, histology, differentiation, T stage, N stage,
      M stage and pTNM stage groups (P > 0.05). Univariate analysis showed that RRM1
      was not an independent prognostic factor (P > 0.05). At the multivariate
      analysis, differentiation and N stage were considered independent prognostic
      factors. CONCLUSIONS: RRM1 expression detected by immunohistology is not an
      independent prognostic factor in NSCLC. TNM stage is still the best prognostic
      factor up to now.

PMID- 21176465
TI  - [A clinicopathological study of 14 cases of pulmonary inflammatory
      myofibroblastic tumor].
AB  - BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is an uncommon disease which
      usually occurs in the lung. Recently, several reports have suggested that IMT is
      a true neoplasm rather than a reactive lesion. In this retrospective study, we
      reviewed clinicopathological characteristics and prognoses of patients with
      surgically resected IMT of the lung at our department. METHODS: From January 1999
      to December 2003, 14 patients had surgical intervention for IMT of the lung at
      Tongji Hospital. The resected lesions were studied histologically and
      immunohistochemically. One to 5 years' follow-up was completed in all patients.
      RESULTS: These 14 patients included eight men and six women. They ranged in age
      from 11 to 46 years old. Nine patients were asymptomatic. The other five
      symptomatic patients had cough, hemoptysis, and dyspnea. For all these patients,
      the diagnostic procedure was surgical excision. The resected tumor size ranged
      from 1.0 to 8.0 cm in diameter. Histologically, a variety of inflammatory and
      spindle cells were observed. The spindle cells corresponded ultrastructurally to
      myofibroblasts or fibroblasts. There was no recurrence in these patients, and all
      of them were in good health during the follow-up. CONCLUSIONS:
      Histopathologically, IMT is characterized by myofibroblasts which are mixed with
      chronic inflammatory cells, including plasma cells, lymphocytes, and histiocytes.
      Surgical resection, when possible, should be chosen as the first choice and
      complete resection leads to excellent survival.

PMID- 21176464
TI  - [Expression and value of hnRNP B1 in sputum of patients with lung cancer by
      immunohistochemistry method].
AB  - BACKGROUND: The expression of heterogeneous nuclear ribonucleoprotein (hnRNP)
      A2/B1 increases significantly in lung cancer tissues. The aim of this study is to
      investigate the expression of hnRNP B1 in exfoliative cells in the sputum of
      patients with lung cancer and its sensitivity and specificity in diagnosis of
      lung cancer. METHODS: The expression of hnRNP B1 in sputum was detected by
      immunohistochemistry (IHC) using anti-hnRNP B1 monoclonal antibody in 70 patients
      with lung cancer and 30 normal subjects (control group). RESULTS: The results of
      sputum exfoliative cytology were 27 positive in 70 samples diagnosed with lung
      cancer, whose sensitivity and specificity were 38.6% and 100.0% respectively. The
      results of sputum immunohistochemistry were 50 positive in 70 samples, with 23
      positive in 29 squamous cell carcinoma and 17 positive in 26 adenocarcinoma and
      10 positive in 15 small cell lung carcinoma. Sputum IHC of hnRNP B1 gave a
      sensitivity of 71.4% and specificity of 93.3%. Sputum IHC of hnRNP B1 was more
      sensitive than sputum exfoliative cytology (P < 0.05). CONCLUSIONS: hnRNP B1
      overexpresses in sputum exfoliative cells and its sensitivity is better than
      sputum exfoliative cytology in diagnosis of lung cancer.

PMID- 21176466
TI  - [A prospective randomized study of adjuvant chemotherapy in completely resected
      stage IIIA-N2 non-small cell lung cancer].
AB  - BACKGROUND: Recently, results from IALT, JBR10 and CALGB9633 showed that
      postoperative adjuvant chemotherapy improved survival rate of patients with non
      small cell lung cancer (NSCLC) after complete resection. The aim of this study is
      to evaluate the effect of postoperative adjuvant chemotherapy on survival after
      complete resection for stage IIIA-N2 NSCLC. METHODS: From Jan 1999 to Dec 2003,
      one-hundred and fifty patients with stage IIIA-N2 NSCLC were randomly divided
      into two groups. The chemotherapy group received four cycles of chemotherapy with
      navelbine or paclitaxel plus carboplatin, while the observation group did not
      receive chemotherapy after operation. RESULTS: In the chemotherapy group, 86.1%
      (68/79) of patients finished 4 cycles of chemotherapy, and no one died of toxic
      effects of chemotherapy; 25% of patients had grade III-IV leukopenia, 2% of
      patients had febrile leukopenia. The median survival time for the entire 150
      patients was 879 days, and 1-, 2- and 3-year survival rate was 81%, 59% and 43%.
      There was no significant difference in median survival between the chemotherapy
      and observation groups (P= 0.0527), but there was significant difference in the 1
      and 2-year survival rate (94.71% and 76.28% vs 88.24% and 60.13%, P < 0.05). The
      most common site of recurrence was the brain. Twenty-six percent (39/150) of
      patients recurred in the brain as their first site of failure, and 22.8% (18/79)
      for the chemotherapy group, 29.6% (21/71) for the observation group. The median
      survival time for patients who developed brain metastasis was not significantly
      different between the chemotherapy and observation groups (812 days vs 512 days,
      P=0.122), but there was significant difference in the 2-year survival rate (66.7%
      vs 37.6%, P < 0.01). The median survival was 190 days for the patients since
      brain metastasis appeared. CONCLUSIONS: Postoperative adjuvant chemotherapy dose
      not significantly improve median survival among patients with completely resected
      stage IIIA-N2 NSCLC, but significantly improves the 1- and 2-year survival rate.
      It also dose not decrease the incidence of brain metastasis but puts off the time
      of brain metastasis.

PMID- 21176467
TI  - [Clinical study of post-operative adjuvant chemotherapy in non-small cell lung
      cancer].
AB  - BACKGROUND: Post-operative adjuvant chemotherapy in non-small cell lung can- cer
      (NSCLC) has been a highlight around the world. The aim of this study is to
      investigate the efficacy of adjuvant chemotherapy on the survival of patients
      with NSCLC after complete resection. METHODS: From June 2000 to December 2003, 64
      patients with stage IB-IIIA NSCLC were divided into the chemotherapy group, who
      accepted adjuvant chemotherapy with navelbine+cisplatin (NP) or taxol+carboplatin
      (TP), and the observation group, who did not accept adjuvant chemotherapy after
      operation. The 1-, 2-, 3- and 4-year survival rate (SR), median survival time
      (MST) and disease-free time (DFT) were analyzed by Kaplan-Meier method. RESULTS:
      The 1-, 2-, 3- and 4-year cumulated SR in the chemotherapy group was 93.9%,
      84.6%, 71.4% and 58.4%, and 93.6%, 83.1%, 63.5% and 43.1% in the observation
      group respectively. There were statistically significant differences in both the
      3- and 4-year survival between the two groups (P < 0.05). The MST was 52 months
      in the chemotherapy group and 47 months in the observation group respectively (P
      < 0.05), and the DFT was 19 months and 16 months respectively (P < 0.05).
      CONCLUSIONS: The cisplatin- or carboplatin-based adjuvant chemotherapy can
      improve the survival of NSCLC patients after complete resection.

PMID- 21176468
TI  - Irinotecan plus cisplatin compared with etoposide plus cisplatin for small cell
      lung cancer: a randomized clinical trial.
AB  - BACKGROUND: Etoposide plus cisplatin (EP) is a standard combination chemotherapy
      regimen for small cell lung cancer (SCLC). The objective of this randomized trial
      is to compare the efficacy and toxicity of combined chemotherapy regimen of
      irinotecan plus cisplatin (IP) with the EP regimen in the treatment of SCLC.
      METHODS: A randomized clinical trial was conducted in which the IP regimen was
      compared with EP regimen in the treatment of patients with SCLC. A total of 61
      patients were randomly divided into IP group (n=30) and EP group (n=31). All
      patients were given more than two chemotherapy cycles. RESULTS: (1)The overall
      response rate was 66.7% in IP group and 61.3% in EP group respectively. The
      complete response was 23.3% in IP group and 16.1% in EP group. There was no
      significant difference in the response rate between the two groups (P > 0.05).
      (2)Severe or life-threatening myelosuppressions such as leucopenia, neutropenia
      and thrombocytopenia were more frequent in EP group than those in IP group (P <
      0.01), and severe diarrhea was more frequent in IP group than that in EP group,
      and there was significant statistical difference (P=0.008). CONCLUSIONS: IP
      regimen is an effective regimen for SCLC. Compared with EP regimen, IP regimen
      has less hematological toxicities but higher diarrhea incidence. The diarrhea of
      irinotecan can be controlled by appropriate treatment.

PMID- 21176469
TI  - [Primary result of the efficacy and tolerance of gefitinib in advanced non-small
      cell lung cancer patients with brain metastasis].
AB  - BACKGROUND: Gefitinib, an orally active epidermal growth factor receptor tyrosine
      kinase inhibitor (EGFR-TKI), has shown targeted antitumor activity in patients
      with advanced non-small cell lung cancer (NSCLC). The aim of this study is to
      evaluate the efficacy and tolerance of gefitinib on brain metastasis in patients
      with NSCLC. METHODS: The clinical characteristics, response to treatment and
      outcome of survival were retrospectively reviewed in eighteen NSCLC patients with
      brain metastasis. All these patients received gefitinib of 250mg/d after brain
      metastasis was diagnosed. They would discontinued the targeted treatment because
      of disease progression or other reasons. Twelve of them received intracranial
      irradiation (group A), while the other six patients didn't (group B). RESULTS:
      The overall response rate and disease controlled rate of gefitinib for brain
      lesions were 27.8% and 88.9% respectively (one complete remission, 4 partial
      remission, 11 stable disease, 2 progressive disease). No correlation among
      gender, smoking status, intracranial irradiation and the response of gefitinib
      was observed. There was no survival difference between the two groups (P=0.192),
      with the median follow-up time of 6 months (range 1-24 months). Rash and diarrhea
      were the most common adverse events. CONCLUSIONS: Gefitinib is active in patients
      with brain metastasis from NSCLC. It is feasible to conduct randomized clinical
      trials to demonstrate the role of targeted treatment for NSCLC patients with
      metastatic brain lesions.

PMID- 21176470
TI  - [A randomized clinical trial on taxol plus oxaliplatin versus taxol plus
      cisplatin as first-line treatment in advanced non-small cell lung cancer].
AB  - BACKGROUND: Paclitaxel plus cisplatin is an effective regimen in the treatment of
      non-small cell lung cancer (NSCLC), but it has severe adverse toxicities. The aim
      of this clinical trial is to evaluate the effect and safety of paclitaxel plus
      oxaliplatin compared with paclitaxel plus cisplatin in the treatment of advanced
      NSCLC. METHODS: From January, 2002 to October, 2004, 83 initially treated
      patients with advanced NSCLC were randomized into two groups: the trial group was
      treated with paclitaxel 175mg/m2, and oxaliplatin 130mg/m2 on day 1;and the
      control group was treated with paclitaxel 175mg/m2 and cisplatin 80mg/m2 on day
      1. Both of them were repeated every 21 days and 2-6 cycles were given to
      patients. The evaluation of efficacy and safety was performed after chemotherapy
      regularly. RESULTS: All patients were evaluable and received 2 cycles
      chemotherapy at least. The response rate of the trial group and control group was
      34.1% (14/41) and 33.3% (14/42) respectively, median time to progression of them
      was 6.0 months and 5.5 months, median survival time was 10.7 months and 10.5
      months, 1-year survival was 39.0% (16/41) and 40.5% (17/42) respectively. The
      following adverse effects of the two groups were different: the incidence rate of
      III+IV leukopenia was 4.9% and 28.6% in the trial group and the control group
      respectively, III+IV thrombocytopemia was 0 and 14.3%, III+IV nausea and vomiting
      was 7.3% and 26.2%. The difference of the incidence rate of III+IV nerve
      abnormality (9.8% and 9.5%), imparied renal function (0 and 7.1%), myalgia and
      anthralgia (0 and 2.4%) was insignificant. CONCLUSIONS: The regimen of paclitaxel
      plus oxaliplatin have the similar efficacy and less adverse toxicities as
      compared to Paclitaxel plus Cisplatin in treatment of advanced NSCLC.

PMID- 21176471
TI  - [Clinical investigation of IRESSA in the treatment of patients with advanced
      refractory non-small cell lung cancer].
AB  - BACKGROUND: Chemotherapy is a main method for patients with advanced non-small
      cell lung cancer (NSCLC). NSCLC is usually a drug-resistant neoplasm. Innate or
      acquired drug-resis-tance contributes to the chief cause for bad effect in the
      treatment of patients with NSCLC. To search for a new anti-cancer drug becomes a
      goal of clinical oncologists. The aim of the present study is to evaluate the
      curative effect and side reactions of IRESSA in the treatment of patients with
      advanced refractory NSCLC. METHODS: The curative investigation was carried out
      after 100-day oral IRESSA by a dosage of 250mg/d in patients with advanced
      refractory NSCLC. The patients had ever experienced at least one regimen of
      chemotherapy. RESULTS: Totally 33 patients enrolled in this study and all were
      stage IV. There were 25 males and 8 females. All enrolled patients except one
      patient who died of severe adverse side reaction completed treatment by IRESSA.
      Thirty-two cases were evaluated. Complete response was obtained in 1 patient
      (3.1%). Partial response was seen in 11 patients (34.4%). The overall effective
      rate was 37.5% (12/32). The disease-control rate was 65.6% (21/32). Time to
      progression was 5.7 months. Overall survival time was 3.3 to 25.9 months (median
      survival time was 9.6 months). One-year survival rate was 28.1% (9/32). Two-year
      survival rate was 6.3% (2/32). The longest survivor lived for 25.9 months. The
      curative effect was correlated with the pathological type, in sequence of
      alveolar cell carcinoma, adenocarcinoma and squamous cell carcinoma. Almost all
      the adverse reactions were acceptable. The main adverse reactions included rash,
      itching of skin, arthralgia, diarrhea, anorexia, nausea, vomiting, dizziness,
      headache, chest distress and abdominal pain. No patients showed abnormal in liver
      or kidney function. No electrocardiogram abnormality was found. One patient who
      had chronic pulmonary fibrosis before died of respiratory failure due to severe
      interstitial pneumonia. CONCLUSIONS: IRESSA takes better effect on the advanced
      drug-resistant patients with NSCLC. So IRESSA may be accepted as third line in
      the treatment of advanced NSCLC and as first line in the treatment of patients
      with bad constitution who have no opportinities for operation, irradiation
      therapy or chemotherapy.

PMID- 21176472
TI  - [Clinical study of HCE regimen in the treatment of small cell lung cancer].
AB  - BACKGROUND: Chemotherapy is main treatment of small cell lung cancer (SCLC). This
      aim of this study is to evaluate the effects and the adverse effects of HCE
      regimen (hydroxycamptothecin + etoposide + carboplatin) in treatment of SCLC.
      METHODS: Patients with previously untreated SCLC were randomized into two groups:
      HCE group (treated by HCE regimen) and EP group (treated by etoposide and
      cisplatin). The chemotherapeutic effects and the adverse effects were compared
      between two groups. RESULTS: A total of 71 patients could be evaluated. The
      overall response rate was 90.3% (28/31) for HCE group with 17 complete response
      (CR) and 11 partial response (PR), and 70.0% (28/40) in the EP group with 9 CR
      and 19 PR. The CR was significantly different between two groups. The median
      survival time of the HCE group and EP group were 11.5 and 25 months respectively.
      The 1-year survival rate was 72.4% vs 69.4% (P > 0.05), 2-year survival rate was
      51.7% vs 44.4% (P < 0.05), and 3-year survival rate was 40.0% vs 29.2% (P <
      0.05). Myelosuppression, diarrhea and vomiting were the main toxicities in two
      groups. The incidence of myelosuppression was higher in the HCE group than that
      in the EP group but without statistical difference (P > 0.05), whereas the
      incidence of nausea and vomiting were significantly lower than that in the EP
      group (P < 0.01). CONCLUSIONS: HCE regimen is an effective regimen for previously
      untreated SCLC with high CR and slight toxicity. It may be worthy of further
      clinical investigation.

PMID- 21176473
TI  - [Therapeutic effect of three dimensional conformal radiotherapy in patients aged
      65 years and older with non-small cell lung cancer].
AB  - BACKGROUND: Three dimensional conformal radiotherapy is one of the important
      treatment methods for patients aged 65 and older with inoperable non-small cell
      lung cancer (NSCLC). The aim of this study is to evaluate the efficacy of three
      dimensional conformal radiotherapy in elderly patients with inoperable NSCLC.
      METHODS: Thirty-one patients aged 65 and older with stage II and III NSCLC were
      treated by three dimensional conformal radiotherapy. Clinical effects, survival
      rates and pulmonary toxicity were analyzed. RESULTS: The overall response rate
      (CR+PR) was 87.1% (27/31). The 1, 2 and 3-year survival rates were 83.9% (26/31),
      51.6% (16/31), and 25.8% (8/31) respectively. The relation of treatment efficacy
      and tumor size was observed. Acute radiation pneumonitis occurred in 3.2% (1/31)
      of the patients. Radiation pulmonary fibrosis occurred in 19.4% (6/31) of the
      patients. CONCLUSIONS: Three dimensional conformal radiotherapy is a safe and
      effective treatment for elderly patients with inoperable NSCLC and has a high
      survival rate.

PMID- 21176474
TI  - [Multivariate analysis of prognosis in 1380 patients with non-small cell lung
      cancer following surgical procedure].
AB  - BACKGROUND: There are many factors that affect the prognosis of non-small cell
      lung cancer (NSCLC). This study aims to analyze the influential factors and
      prognosis in patients with NSCLC following operation. METHODS: From January 1996
      to January 2003, 1380 patients with NSCLC treated surgically were retrospectively
      studied. The correlation between clinicopathological characteristics and
      prognosis was evaluated by univariate and multivariate analyses. RESULTS: In the
      whole group, 1-, 3- and 5-year survival rate was 78.85%, 49.78% and 38.96%
      respectively, and median survival time (MST) was 38.77 months. According to
      univariate analysis, tumor size, pathologic type, clinical type (central or
      peripheral), TNM stages, lymph node involvement, surgical procedure,
      postoperative chemotherapy, and cycles of chemotherapy were significantly related
      to the survival of patients. By multivariate analysis, tumor size, TNM stages,
      lymph node status and postoperative chemotherapy were independent prognostic
      factors. CONCLUSIONS: Tumor size, TNM stages, lymph node involvement and
      postoperative chemotherapy are independent prognostic factors for NSCLC following
      the surgical procedure.

PMID- 21176475
TI  - [Clinical analysis of surgically treated patients with adenosquamous carcinoma of
      the lung].
AB  - BACKGROUND: Adenosquamous carcinoma of the lung is a rare pathologic type of lung
      cancer. The aim of this study is to explore the clinical features of
      adenosquamous carcinoma of the lung. METHODS: A total of 115 patients with
      adenosquamous carcinoma of the lung were retrospectively analysed, who were
      diagnosed by operation and pathology. RESULTS: Among the 36 female patients, 7
      were under 49 years (19.44%). There were 14 patients (12.17%) without any symptom
      and 16 patients had residual carcinoma at the resection margin (14.04%). The
      degree of lymph node metastasis was 37.51%. The proportion of stage III patients
      was 54.78%. CONCLUSIONS: The incidence of adenosquamous carcinoma of the lung in
      young women (under 49 years, especially under 39 years) is rather high. The
      residual carcinoma at the resection margin often occurs after routine operation.
      The degree of lymph node metastasis is rather high.

PMID- 21176476
TI  - [Improve multicenter investigation of emerging infectious diseases in children].

PMID- 21176477
TI  - [Use of flexible fiberoptic bronchoscopy in pediatric clinical practice].

PMID- 21176478
TI  - [Change in bacterial pathogens in community-acquired pneumonia in children].

PMID- 21176479
TI  - [Multi-center investigation of the hospitalized children with 2009 influenza A
      (H1N1) infection].
AB  - OBJECTIVE: The pandemic influenza in 2009 was caused by a new virus, influenza A
      (H1N1) virus which has never been found in human before. The papers published at
      different time, in different places by authors from different institutions show
      different clinical features. Herein, we describe the clinical features of
      hospitalized children with 2009 influenza A (H1N1) infection from multi-centers
      all over the country retrospectively. METHODS: Clinical data of 810 cases with
      2009 influenza A (H1N1) infection were collected from 17 hospitals. The clinical
      characteristics, laboratory abnormalities, treatment and outcomes were
      retrospectively studied. RESULT: Of the 810 hospitalized children with 2009
      influenza A (H1N1) infection, 508 (62.7%) were male, 302 (37.3%) female; the
      median age was 43 months, 550 (67.9%) were under 5 years of age; 148 (18.5%) had
      underlying chronic disease. The common presenting symptoms were fever (96.3%),
      runny nose (36.3%), stuffiness (23.7%), sore throat (18.1%), cough (93.7%),
      sputum (42.8%), wheezing (27.0%), dyspnea (20.1%), vomiting (16.0%), diarrhea
      (8.1%), irritability (9.8%), lethargy (7.9%) and seizures (4.0%). The common
      laboratory abnormalities were abnormal results of white blood cells counts
      (46.5%), elevations of lactate dehydrogenase (LDH, 42.7%), elevated C-reactive
      protein (CRP, 37.8%), aspartate transaminase (AST, 31.7%) and creatine kinase
      (CK, 21.5%). Clinical complications included pneumonia 586 (72.3%),
      encephalopathy/encephalitis 49 (6.0%), and myocarditis 30 (3.7%); 183 children
      had critical illness. The incidence of having underlying chronic disease,
      leukocytosis, neutrophilia, lymphopenia and elevations of CRP were high in
      critically ill patients. Totally 19 (2.3%) died, 8 died from
      encephalopathy/encephalitis; 10 died from severe pneumonia and ARDS, of whom 5
      patients were complicated with encephalopathy/encephalitis; 1 died from secondary
      fungal meningitis. CONCLUSION: Hospitalized children with 2009 influenza A (H1N1)
      infection may have a wide involvement of organ systems. The risk factors for
      critical illness were having underlying chronic disease, leukocytosis,
      neutrophilia, lymphopenia and elevations of CRP. Complications of severe
      pneumonia, ARDS, and encephalopathy/encephalitis were main causes of death.

PMID- 21176480
TI  - [Identification and typing of adenoviruses from pediatric patients with acute
      respiratory infections in Beijing from 2003 to 2008].
AB  - OBJECTIVE: Adenovirus (ADV) is one of the most common causes of acute respiratory
      infections in infants and children. The objective of this study was to
      investigate the prevalence of adenovirus infection among pediatric patients with
      acute respiratory infections in Beijing and the types of the adenoviruses
      circulating in Beijing on the molecular bases. METHOD: Clinical specimens
      including throat swabs from outpatients and nasopharyngeal aspirates from
      hospitalized patients were collected from patients with acute respiratory
      infections in a consecutive period of 6 years from Jan 2003 to Dec 2008.
      Adenoviruses were identified from the collected clinical specimens by tissue
      culture and/or immunofluorescence assay and typed by nested-PCR based on the
      sequence of the encoding gene of hexon. Primers were designed for PCR
      amplification using hexon gene of adenovirus as target. One primer pair was
      designed as universal primers for amplifying a 1278 bp gene fragment located at
      the hexon gene of adenovirus types 3, 7, 11 and 21. Four primer pairs with the
      sequences located within the region of this 1278 bp fragment were designed
      specifically for amplifying adenoviruses types 3, 7, 11 or 21, respectively,
      which were used for a multiplex nest-PCR in a single tube. The products from this
      multiplex nest-PCR were 502 bp (for type 3), 311 bp (for type 7), 880 bp (for
      type 11) and 237 bp (for type 21), respectively, and the type of the adenovirus
      tested can be determined after agarose electrophoresis analysis of the PCR
      products. For those strains which could not be typed by the multiplex nest-PCR,
      the gene fragment was amplified by a universal primer pair for all adenovirus
      types from group A to F and the PCR products were sequenced directly. RESULT: Out
      of 17 941 clinical specimens collected, including 4378 throat swabs from
      outpatients and 13 563 nasopharyngeal aspirates from hospitalized patients, 304
      were adenovirus positive by tissue culture and/or immunofluorescence assay, the
      overall positive rate was 1.69% (304/179 41). Among these 304 adenovirus positive
      specimens, 184 were by virus isolation and 184 by immunofluorescence assay, among
      which 64 were positive by both methods. The types of the adenoviruses were tested
      for 285 patients including 174 viral isolates and 111 clinical specimens. By
      using the multiplex nest-PCR, 272 were typable, including 174 (61.1%, 174/285)
      for ADV3, 92 (32.3%, 92/285) for ADV7, 6 for ADV11 (2.1%, 6/285) and no
      adenovirus type 21 was detected. Sequence analysis for those 13 nontypable
      specimens by the multiplex nest-PCR showed that 9 were ADV2 (3.2%, 9/285), 2 were
      ADV6 (0.7%, 2/285), 1 was ADV1 (0.4%, 1/285) and 1 was ADV5 (0.4%, 1/285). Most
      of the patients positive for adenovirus were under 5 years of age and 64.4% were
      from patients with lower respiratory infections, such as bronchiolitis and
      pneumonia. All the 5 cases of severe pneumonia with pulmonary failure were caused
      by ADV7 infection. CONCLUSION: Adenovirus is still an important pathogen for
      acute respiratory infection in infants and young children and most of the
      adenoviruses associated with acute respiratory infections in children in Beijing
      from 2003 to 2008 were ADV3 and ADV7. ADV7 could cause severe lower respiratory
      infections.

PMID- 21176482
TI  - [Multicenter clinical investigation of pertussis in children and adolescents with
      persistent cough].
AB  - OBJECTIVE: Pertussis is an acute respiratory tract infection caused by Bordetella
      pertussis. This disease, though preventable by vaccination, the resurgence or
      persistence was reported frequently in developed countries. The current clinical
      epidemiology of pertussis in China is scarcely known. In this multicenter
      clinical study, we investigated the prevalence of pertussis in children and
      adolescents with persistent cough in Shanghai, Chongqing, Kunming and Yinchuan.
      METHOD: The nasopharyngeal swabs and serum (single) were collected from subjects
      aged >= 6 years with cough for more than 2 weeks during November 2008 to October
      2009. The culture and multiplex PCR assays were used to identify the B.
      pertussis, and ELISA assay (Viron/serio, Germany) was used to test the antibody
      to pertussis toxin (PTIgG). The laboratory confirmed B. pertussis were culture
      positive and or PCR positive, and or PTIgG > 80 FDA-U/ml (single serum). RESULT:
      Totally 1001 subjects were enrolled; 93.5% of subjects were immunized with
      diphtheria-pertussis-tetanus vaccine (DPT). The subjects were divided into group
      1 aged from 6 to 8 years, group 2 (age -10 years), group 3 (age -12 years) and
      group 4 (age -18 years). The numbers of subjects of the four groups were 307,
      249, 212, and 233; 113 subjects were B. pertussis positive (11.3%), 888 subjects
      were B. pertussis negative. The infection rates of the four groups were 7.2% (22,
      307), 11.2% (28, 249), 10.4% (22, 212) and 17.6% (41, 233) respectively (chi(2) =
      2915.2, P < 0.01). The total infection rate in Shanghai was 16.7% (65, 402),
      which was higher than that in the other regions (chi(2) = 3003.0, P < 0.01).
      CONCLUSION: Although the immunization rates of DPT is high, B. pertussis
      infection is still an important etiological factor associated with persistent
      cough in children and adolescent. Doctors and the laboratory staff should pay
      attention to diagnosis of pertussis.

PMID- 21176481
TI  - [Molecular epidemiological and clinical features of coronavirus HKU1 in children
      with acute respiratory tract infection in Lanzhou].
AB  - OBJECTIVE: Human coronavirus (CoV)-HKU1 (HCoV-HKU1) was first isolated by Woo et
      al in Hong Kong. Several successive reports confirmed retrospectively that this
      new human coronavirus was circulating in different countries worldwide. However,
      the impact and the role of the emerging HCoV-HKU1 were not defined in children
      with ARTI. The objective of this study was to investigate the molecular
      epidemiology and clinical characteristics of HCoV-HKU1 infection in children with
      ARTI in Lanzhou, China. METHOD: Nasopharyngeal aspiration (NPA) samples were
      collected from 301 children with ARTI at the First Hospital of Lanzhou
      University, Gansu Province, China, between November 2007 and October 2008.
      Demographic data and clinical findings of these children were collected at the
      same time. The informed consent was obtained from their parents. This study
      protocol was approved by the hospital ethics committee. The reverse transcription
      polymerase chain reaction (RT-PCR) was employed to screen HCoV-HKU1. Furthermore,
      other common respiratory viruses were screened in HCoV-HKU1 positive samples. All
      PCR positive products were sequenced, and phylogenetic analysis was conducted.
      RESULT: The overall frequency of HCoV-HKU1 infection was 5.0% (15/301). The HCoV
      HKU1 pol gene sequences shared a 95.8% - 99.6% nucleotide identity with the human
      coronavirus-HKU1 strain, whereas the amino acid identity was 90.7% - 99.3%. The
      phylogenetic analysis revealed that the HCoV-HKU1 strain pol gene clustered with
      the HCoV-HKU1 strain N15 genotype B (no. DQ415911); 11 of 15 HCoV-HKU1 positive
      sample tested were mixed-infection. HCoV-HKU1 was detected only from November to
      April. Positive specimens peaked in November. Children with HCoV-HKU1 infection
      varied in age from 15 day to 12-years (median age, 10 months). The clinical
      diagnoses of HCoV-HKU1 positive patients included those with AURI and LURI. The
      clinical presentations of HCoV-HKU1 positive children included fever, cough,
      sputum production, diarrhea, vomiting; pharynx engorgement, crackles, and
      wheezing. The mean hospital stay of the 14 patients was 9.9 days. Six of 15 HCoV
      HKU1 positive patients had an underlying illness, and they were all inpatients
      (hospital stay, mean, 11.2 days). There was no statistically significant
      difference in the detection rate between the two groups with and without
      underlying illnesses. CONCLUSION: Human CoV-HKU1 infection exists in children
      with respiratory tract infections in Lanzhou region. A single HCoV-HKU1 genotype
      B was circulating locally. The symptoms and clinical diagnoses of those infected
      with HCoV-HKU1 had no specificity as compared with patients with other common
      respiratory viruses infection.

PMID- 21176483
TI  - [Application of bronchoalveolar lavage in the etiological diagnosis of childhood
      pulmonary infections].

PMID- 21176484
TI  - [The role of bronchoscopy in diagnosis and treatment of bronchial tuberculosis in
      children].

PMID- 21176485
TI  - [Clinical characteristics of autoimmune hepatitis in 11 children].
AB  - OBJECTIVE: To investigate the clinical features of autoimmune hepatitis (AIH) in
      children so as to improve the awareness of the disease. METHOD: The medical
      records of 12 children who were clinically diagnosed as AIH between 2004 and 2008
      were reviewed. The scoring system of the International Autoimmune Hepatitis Group
      (IAIHG) for diagnosis of AIH was used to confirm the diagnoses. Clinical
      manifestations, laboratory examinations, liver pathology results and prognosis
      were retrospectively analyzed. RESULT: Eleven patients were diagnosed as AIH by
      the scoring system and 10 of them were type I, one had not been typed. The
      average time from onset to diagnosis was (7.5 +/- 7.4) months. Seven patients
      (63.6%) had acute onset, among them 2 cases progressed to subacute severe
      hepatitis, 3 (27.3%) had deliquescence onset and 1 (9.1%)was complicated with
      hepatic cirrhosis. Levels of serum globulin and IgG were tested and were higher
      in 10 cases (90.9%) with average (39.4 +/- 7.4) g/L and (31 +/- 12) g/L
      respectively. Antinuclear antibodies (ANA) were measured positive in 10 cases,
      and 1 was anti-smooth muscle antibody (SMA) positive. Liver-kidney microsomal
      antibody (LKM-1) and anti-mitochondrial antibody (AMA) were detected in none of
      them. The liver pathology of 11 cases could be divided into acute and chronic
      hepatitis in 5 and 6 cases, respectively. Severe submassive liver necrosis and
      severe fibrosis were identified in 3 cases respectively. Lymphocytes
      infiltration, interfaces hepatitis and rosette-like annulation of hepatocytes
      were found in 81.8%, 36.4%, and 18.2% of cases on liver pathology. Eleven
      patients were followed up with therapy of single glucocorticoids or
      glucocorticoids combined with immunosuppressive agents. The disease of 2 cases
      deteriorated and 3 cases died. One case was still under therapy, 1 case was
      stabilized and 4 cases had recurrence. CONCLUSION: The children with AIH had
      diverse symptoms, signs, onsets and laboratory test results. The liver
      pathological changes were less typical. Rate of misdiagnosis was high in early
      stage. Prognosis was poor in most cases even though properly treated. Therefore
      close attention needs to be paid to children with AIH.

PMID- 21176486
TI  - [Bronchitis obliterans in children: report of two cases and literature review].
AB  - OBJECTIVE: Bronchitis obliterans is a severe and extremely rare complication of
      respiratory tract infections in children and is characterized by massive
      atelectasis and collapse of the affected lung. METHOD: The clinical
      manifestations, characteristic imaging of two cases with bronchitis obliterans
      were summarized. RESULT: These two cases complained of cough and episodes of
      wheezing with exercise. Chest auscultation revealed bronchial breath sounds on
      the right side. High-resolution computed tomography (HRCT) scan showed
      atelectasis of the right lung and dilated central airways. Mycoplasma complement
      fixation antibody (CF-Ab) titer was 1:320. The diagnosis of bronchitis obliterans
      was made according to the current diagnostic criteria. They were treated with low
      dose erythromycin [5 mg/(kg * d)], ultrasonically nebulized Pulmicort inhalation,
      and regular bronchoscopic lavage. Follow-up of the two cases showed that case one
      had a partial lung re-expansion after six months, but case two had no significant
      improvement. CONCLUSION: In the process of diagnosis of atelectasis, bronchitis
      obliterans should be noticed. A conservative treatment is effective in certain
      cases, but pneumonectomy or lobectomy should only be considered as the last
      option.

PMID- 21176487
TI  - [Application of flexible bronchoscopy in diagnosis and treatment of 104 children
      with pulmonary atelectasis].
AB  - OBJECTIVE: To evaluate the value of flexible fiberoptic bronchoscopy in diagnosis
      and treatment of pulmonary atelectasis in children. METHOD: Totally 104 patients
      with pulmonary atelectasis, who were admitted to this department, received
      flexible fiberoptic bronchoscopy from January 2006 to May 2010, were enrolled in
      a retrospective analysis. RESULT: The analysis on causes of pulmonary atelectasis
      showed that 76 cases (73%) of the 104 patients had sputum obstructions, which was
      the main cause of atelectasis. Thirteen cases (13%) had bronchopulmonary
      dysplasia, 9 cases among these were infants. Twelve cases (12%) had foreign body
      aspiration, 8 cases among these were under the age of 3-year. After flexible
      fiberoptic bronchoscopy, 100 cases got expansion of pulmonary atelectasis. Sixty
      five of the sputum obstruction cases got atelectasis reexpansion after one time
      of flexible fiberoptic bronchoscopy. Eight of the sputum obstruction cases got
      atelectasis reexpansion after two times of flexible fiberoptic bronchoscopy. Two
      of the sputum obstruction cases got atelectasis reexpansion after three times of
      flexible fiberoptic bronchoscopy. The rate of atelectasis reexpansion after one
      time of alveolus lavement was higher in the cases whose courses of disease were
      under 3 weeks, than in the cases whose courses of disease were beyond 3 weeks.
      CONCLUSION: Etiology of pulmonary atelectasis varied at different age. The
      morbidity of bronchopulmonary dysplasia was high in infants. Foreign body
      aspiration was the common cause of pulmonary atelectasis in children from 1 to 3
      year of age. Sputum obstruction was the main cause of pulmonary atelectasis in
      over 3-year-old children. Most cases got atelectasis reexpansion after alveolar
      lavage. The patients who had shorter course of disease might have higher rate of
      atelectasis reexpansion after alveolar lavage once. Flexible fiberoptic
      bronchoscopy plays an important role in diagnosis and treatment of pulmonary
      atelectasis.

PMID- 21176488
TI  - [Diagnostic value of serum levels of beta-human chorionic gonadotropin (beta-hcG)
      combined with beta-hcG in cerebrospinal fluid for determining locations of
      germinomas in children with precocious puberty].
AB  - OBJECTIVE: To study the clinical manifestations of germinoma in children with
      precocious puberty and to evaluate the diagnostic value of serum levels of beta
      human chorionic gonadotropin (beta-hcG) combined with detections of beta-hcG in
      cerebrospinal fluid (CSF). METHOD: Twelve male children with germinomas confirmed
      by pathology from Jan. 2005 to Dec. 2009, aged from 4.2 to 10.2 years, were
      enrolled in this study. Patients were classified into two groups according to
      tumor locations: intracranial group and non-intracranial group. Levels of beta
      hcG in serum as well as in CSF were detected before the initiation of therapy.
      Age and gender matched 5 children undergoing lumbar puncture for other diseases
      were set as control group for the determinations of beta-hcG in CSF. Levels of
      beta-hcG and testosterone in serum and CSF were compared between intracranial
      group and non-intracranial group, and levels of beta-hcG in CSF were compared
      between non-intracranial group and control group. RESULT: The 12 children showed
      elevated serum levels of testosterone: 10.43 (1.70-254.00) ug/L, 11 children had
      testicular volume > 4 ml, while response to LHRH stimulation tests were low; 6
      children had gynecomastia. Serum levels of beta-hcG were elevated in both
      intracranial and non-intracranial group and no significant differences were found
      between groups 63.75 (8.50-309.50) IU/L vs. 59.00 (25.10-71.77) IU/L, P = 0.644.
      No correlations were found between serum levels of beta-hcG and ages, tumor
      locations, and courses of the patients. Levels of beta-hcG in CSF were
      significantly higher in intracranial group than that in non-intracranial group
      488.99 (17.30-1048.53) IU/L vs. 1.20 (1.20-1.50) IU/L, P = 0.009. Children with
      non-intracranial germinomas had similar levels of beta-hcG in CSF as that in
      control group (P = 0.571). CONCLUSION: The main clinical manifestations in boys
      suffered from germinoma included pseudo-precocious puberty, disproportionate
      testicular volume and gynecomastia. Detection of serum levels of beta-hcG
      combined with beta-hcG levels in CSF may be useful for determination of the
      locations of germinomas in children with precocious puberty.

PMID- 21176489
TI  - [Neonatal diabetes mellitus: a clinical analysis of 13 cases].
AB  - OBJECTIVE: To study the clinical features of neonatal diabetes mellitus (NDM).
      METHOD: Thirteen cases with NDM were seen in our department between Jul. 2004 and
      Sept. 2009. Their clinical features were reviewed retrospectively. RESULTS: The
      average birth weight of the 13 cases was 2.30 kg. The median age at diagnosis was
      2 months. The mean blood glucose at diagnosis was 22.2 mmol/L. Symptoms in 9 of
      13 cases were exacerbated by infection and only 5 had typical symptoms of
      diabetes mellitus including polydipsia, polyuria, polyphagia and body weight
      loss. The common clinical findings included athrepsia, diuresis, and moderate
      dehydration. Ketoacidosis attacked 3 cases and 3 children had
      hypertriglyceridemia, meanwhile, 2 children had complications of blood clotting
      dysfunction and congenital cardiopathy, respectively. Autoantibody to insulin
      (IAA) was tested in 11 cases, all but one case was negative. Glycosylated
      hemoglobin was increased in 6 cases. Insulin treatment was started in all the 13
      cases. The initial dose was 0.56-1.00 U/(kg * d), and the maximal dose was 1.35
      U/(kg * d) depending on the variety of blood glucose. Blood glucose decreased
      significantly within 24 hours. Unfortunately, 1 case developed progressive blood
      glucose decline and recurrent hypoglycemia. Symptoms of the 3 cases who developed
      DKA were relieved 48 hours later, and their blood glucose was well under control.
      Among the 8 cases followed up, 4 had TNDM and 2 had PNDM. Unfortunately, 1 case
      died at the age of 3 months because insulin injection was stopped by the parents.
      CONCLUSION: Early diagnosis and prompt management may lead to favorable
      prognosis. Blood glucose monitoring is a valuable method to avoid misdiagnosis
      and NDM should be differentiated from stress hyperglycemia, iatrogenic, or other
      causes of hyperglycemia.

PMID- 21176490
TI  - [Clinicopathological characteristics and potential etiologies of neonatal
      spontaneous gastric perforation].
AB  - OBJECTIVE: To study the etiology and clinicopathological features of neonatal
      spontaneous gastric perforation. METHODS: The clinical data of 15 cases with
      neonatal gastric perforation seen from 2001 to 2009 were retrospectively
      analyzed. Immunohistochemical staining was adopted for all the cases. RESULTS:
      The typical clinical manifestations of this disease were vomiting, abdominal
      distention and respiratory distress. Abdominal orthostatic X-ray showed free gas
      under diaphragm and seroperitoneum. In most of the cases the stomach perforation
      occurred at the greater curvature. Eight of the cases died in this group, the
      mortality was 53.33%. Six of the deaths occurred within 1 day after birth with
      symptoms. There were thinning and defect of stomach wall muscle and interstitial
      cells of Cajal (ICC) reduction as demonstrated by microscope. CONCLUSIONS:
      Spontaneous neonatal gastric perforation is associated with abnormal gastric wall
      structure and reduction of ICC. Prognosis is closely related to the time of onset
      and the timely surgical operation.

PMID- 21176491
TI  - [Clinical manifestation and EEG characteristics of Angelman syndrome].
AB  - OBJECTIVE: To investigate the clinical manifestations and EEG characteristics of
      Angelman syndrome in children, and to strengthen the recognition of this disease.
      METHOD: Fourteen children with Angelman syndrome received video EEG monitoring,
      head MRI/CT and gene test, 11 patients received the metabolic investigations
      (e.g., lactic acid, ammonia, GC/MS and MS/MS). Eight patients received Gesell
      test. The patients were followed up for 1-3 years. RESULT: Of the 14 cases, 4
      were male and 10 female, their age was from 8 months to 3 years and 7 months. The
      clinical characteristics included prominent lower jaw and wide mouth, fair skin
      and yellow hair, light-colored iris, paroxysmal laughter, astasia and language
      backward. Twelve patients had epileptic seizures; 10 patients displayed non
      convulsive status epilepticus (NCSE), 9 patients displayed myoclonic, atypical
      absence, and non-convulsive seizure simultaneously; myoclonic, generalized tonic
      clonic seizure and complex partial seizure in 1 each; 4 patients had fever in
      early seizures. The EEG showed paroxysmal middle-high amplitude 2-3 Hz spike and
      spinous slow-wave in 8 patients. Four patients showed paroxysmal frequently
      middle-high amplitude 2-3 Hz slow waves mixed with sharps. The other 2 patients
      showed a normal EEG. All the patients were diagnosed with genetics testing. The
      results included maternal deletion of chromosome 15q11-13 in 12, paternal
      uniparental disomy in 1 and imprinting defects in 1. CONCLUSION: There are
      characteristic clinical manifestation and craniofacial features in Angelman
      syndrome patients. Some patients have specific EEG patterns. Abnormal region of
      chromosome 15q11-13 is the basis of diagnosis.

PMID- 21176492
TI  - [Neurocutaneous melanosis presenting with intracranial canceration to melanoma
      from leptomeningeal melanin infiltration].

PMID- 21176493
TI  - [Molecular regulatory mechanism of intrauterine growth retardation].

PMID- 21176494
TI  - [Progress in studies on microRNAs regulation of cardiac development].

PMID- 21176496
TI  - [Summary of the 2010 National Conference on Pediatric Cardiovascular Diseases].

PMID- 21176495
TI  - [Mast cells and cardiovascular disease].

PMID- 21176497
TI  - [To make prominent of immunocompromised patients with lung infection].

PMID- 21176498
TI  - [Difficulties in clinical diagnosis and treatment of immunocompromised patients
      with pulmonary complications].

PMID- 21176499
TI  - [Diagnostic strategies of immunocompromised patients with pulmonary
      complications].

PMID- 21176500
TI  - [The pathogenic analysis of 120 acquired immune deficiency syndrome patients with
      pulmonary infections via bronchoscopy].
AB  - OBJECTIVE: To evaluate the clinical value of bronchoscopy in the pathogenic
      diagnosis of AIDS patients with pulmonary infections and to illustrate the
      constituent ratio of different pulmonary pathogens. METHODS: From August 2006 to
      September 2009, we performed bronchoscopies to 120 AIDS patients who had
      pulmonary infections. We described the manifestations under the bronchoscope and
      each patient underwent bronchoalveolar lavage for further detection including
      bacterial culture and pathological test. We also took biopsies in patients who
      had obviously abnormal lesions under the bronchoscope.At the same time, we
      collected the clinical information for analyzing. RESULTS: Among 120 patients, we
      found 30 cases of mycobacteria infection, 25 cases of bacterial infection, 12
      cases of PCP, 5 cases of fungal positive, 3 cases of CMV. Bronchial mucosa
      biopsies were taken in 26 patients, 12 cases of chronic inflammation, 7 cases of
      granulomatous inflammation, 4 cases of squamous cell carcinoma, 2 cases of
      adenocarcinoma and 1 case of lymphoma. CONCLUSION: Bronchoscopy is a very useful
      tool and it's of great value for pathogenic detection in AIDS patients with
      pulmonary infections. At present, in China the main pulmonary infections in AIDS
      patients are TB, bacterial infection and PCP.

PMID- 21176501
TI  - [Fusarium solani infection in a patient after allogeneic hematopoietic stem cell
      transplantation: case report and literature review].
AB  - OBJECTIVE: To study Fusarium solani infection as a complication in patients after
      allogeneic hematopoietic stem cell transplantation and to discuss the diagnosis
      and appropriate therapy. METHODS: Symptoms, physical examination, laboratory
      tests, computed tomographic (CT) scans, treatments and outcomes of Fusarium
      solani infection in a patient with acute myeloid leukemia after allogeneic
      hematopoietic stem cell transplantation were retrospectively analyzed, and
      related literatures reviewed. RESULTS: The patient developed pulmonary
      infiltration and systemic multiple subcutaneous masses after allogeneic
      hematopoietic stem cell transplantation. Tissue biopsy smear showed a large
      number of hyphae and spores, and fungal culture grew Fusarium solani. The
      subcutaneous masses were incised and drained, while amphotericin B and
      voriconazole were administered, with granulocyte colony-stimulating factor (G
      CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) for
      hematopoietic recovery. The patient was discharge after full recovery.
      CONCLUSION: Fusarium solani infection is a rare but fatal complication after
      allogeneic hematopoietic stem cell transplantation. Once the skin lesions or
      subcutaneous masses developed, tissue smear and culture should be done as soon as
      possible. Early diagnosis and effective treatment to recovery of the patient
      after allogeneic hematopoietic stem cell transplant. Moreover, the recovery of
      adequate neutrophil levels is the most important factor in the resolution of
      fusarial infection.

PMID- 21176502
TI  - [N-cadherin as a receptor for adhesion and endocytosis of Aspergillus fumigatus
      by human umbilical vein endothelial cells].
AB  - OBJECTIVE: To study the receptor for adhesion and endocytosis of Aspergillus
      fumigatus hyphae by human umbilical vein endothelial cells (HUVEC). METHODS:
      Aspergillus fumigatus hyphae were incubated with the total protein of HUVEC for
      investigating the binding of N-cadherin and the fungus. After the model of
      adhesion and endocytosis of Aspergillus fumigatus by HUVEC was established, the
      capacity of adhesion and endocytosis was evaluated with the presence of the
      antibody to N-cadherin. RESULTS: N-cadherin sticked to the surface of Aspergillus
      fumigatus. Adhesion and endocytosis were inhibited with the presence of the
      antibody to N-cadherin. CONCLUSION: N-cadherin is a receptor for adhesion and
      endocytosis of Aspergillus fumigatus by HUVEC.

PMID- 21176503
TI  - [The application of endobronchial ultrasound-guided transbronchial needle
      aspiration: report of 70 cases].
AB  - OBJECTIVE: To evaluate the diagnostic yield and the safety of endobronchial
      ultrasound-guided transbronchial needle biopsy (EBUS-TBNA) in mediastinal and
      hilar lymph nodes and lung tumors. METHODS: EBUS-TBNA was performed in 70
      patients with thoracic masses or mediastinal-hilar lymphoadenopathy proved by CT
      scan. RESULTS: From July 2009 to January 2010, 70 patients were included in the
      study. EBUS-guided TBNA was performed to obtain samples from mediastinal and
      hilar lymph nodes (120 stations) and lung tumors (11 masses). In 46 cases of
      newly diagnosed lung cancer, 44 were confirmed by EBUS-TBNA without on site
      cytology assistance, with 2 false negative cases. The sensitivity, specificity,
      positive predictive value, negative predictive value, and accuracy of EBUS-TBNA
      in the diagnosis of lung cancer were 96%, 100%, 100%, 92% and 97% respectively.
      Non-caseous granuloma formed by epithelioid cells was found in EBUS-TBNA
      histological specimen from 5 out of 10 patients with clinically diagnosed
      sarcoidosis. TBNA cytological smear showed acid-fast bacilli and histology of the
      lymph node demonstrated coagulatory necrosis from 1 out of 4 tuberculous cases.
      The procedure was uneventful, and there were no complications. CONCLUSION: EBUS
      TBNA is an effective and safe method for the diagnosis of bronchogenic carcinoma
      and unknown mediastinal-hilar lymphadenopathy.

PMID- 21176504
TI  - [A pathogenic and clinical study of 882 cases of adult influenza-like illness in
      Guangzhou].
AB  - OBJECTIVE: This study was undertaken to describe the viral etiology and clinical
      features in patients with influenza-like illness (ILI) in Guangzhou. METHODS: The
      nasopharyngeal and throat swabs were collected from 882 patients presenting with
      ILI between January and September, 2009. Viral pathogens were cultured and
      identified by immunofluorescence technique using the Shell-Vial method. The
      clinical data were statistically analyzed. RESULTS: (1) Viral etiology. Of the
      882 samples, 385 (43.7%) were confirmed to have at least one of the 9 different
      respiratory viruses detected. Among these viral isolates, 67.3% (259/385) were
      seasonal influenza A virus, 27.8% (107/385) were influenza B virus, and 1.3%
      (5/385) were human parainfluenza virus (PHIV) 1, 2, or 3. In addition, 2 cases
      (0.5%) of each adenovirus, HSV-1, enterovirus and respiratory syncytial virus
      (RSV) were also found in the samples. Co-infections with more than one virus were
      revealed in 8 (2.1%) of 385 samples tested, among them 6 samples were mixture of
      influenza A and influenza B, 1 sample was positive for both influenza B virus and
      HPIV-3, and 1 was for both adenovirus and RSV. Seasonal influenza B virus
      appeared endemic between March and May, and seasonal influenza A virus became
      dominant between June and August. (2) Clinical features. The percentage of
      patients aged from 18-30 years was much higher than that of other age groups. The
      most common symptoms were moderate fever and sore throat, followed by cough. The
      percentage of upper respiratory infection and pneumonia was 88.4% (727/882) and
      10.7% (95/882) respectively. Clinical features did not discriminate between
      patients with seasonal influenza A and those with influenza B virus infection.
      The average numbers of leukocytes and lymphocytes were lower in the group
      positive for influenza viruses than in virus negative group. The patients with
      adenovirus, HPIV and RSV infection were significantly younger. No rash was
      observed in patients with enterovirus or HSV infection. CONCLUSIONS: (1) Seasonal
      influenza virus was the major viral etiologic agent of ILI in Guangzhou during
      the first 9 months in 2009. Influenza B and A viruses seasonally prevailed in
      spring and summer, respectively, while other viral etiologic agents appeared to
      be sporadic. (2) The analysis of clinical features in patients with ILI indicated
      that fever was the most common symptom, with body temperature varying greatly,
      and may be associated with evident respiratory and occasionally systemic
      symptoms. Among the cases with viral infection, the upper respiratory
      presentation was universal, and pneumonia was frequently noticed.

PMID- 21176505
TI  - [The relationship between chest CT findings and viral load in patients with novel
      influenza A (H1N1)].
AB  - OBJECTIVE: To evaluate the value of chest CT findings and dynamic changes of
      viral load in patients with novel influenza A (H1N1) infection in clinical
      diagnosis, differential diagnosis and treatment. METHODS: Fifty-one patients with
      confirmed novel influenza A (H1N1) according to the diagnostic criteria of the
      Ministry of Health, received chest X-ray, CT scans (HRCT) and viral load tests in
      our hospital from May to December of 2009. Based on whether there were signs of
      pneumonia in CT imaging, the patients were divided into a pneumonia group (n =
      31) and a non-pneumonia group (n = 20). The relationship between chest CT changes
      and viral load was observed and analyzed statistically using SPSS 10.5 software.
      RESULTS: Patchy consolidations of lungs were the main findings in pneumonia group
      with influenza A (H1N1) infection, and ground-glass opacities were the main CT
      findings at acute and convalescent phases. Lobular and segmental shadows of the
      lungs were diffusely distributed, mostly found in lower lungs, especially the
      left lung. In some cases, the lung diseases were accompanied with mediastinal
      lymphadenopathy. Co-existence of pulmonary parenchymal, interstitial and pleural
      diseases was observed. Peak viral load occurred at the early phase of illness,
      with the mean initial viral load being 7.7 copies/ml and 4.2 copies/ml in the
      pneumonia and the non-pneumonia groups respectively. The viral nucleic acid
      became negative 4 days after antiviral treatment (course of 6 days). Dynamic
      observation of 3 patients with novel influenza A (H1N1) pneumonia showed that,
      the viral clearance period preceded the absorption of lung lesions in 2 cases,
      but viral clearance period of a young patient was significantly prolonged.
      CONCLUSION: In patients with the novel influenza A (H1N1) infection, the viral
      load in the pneumonia group was significantly higher than that in the group with
      normal chest imaging. Dynamic observation on chest imaging and viral load may be
      beneficial for clinicians to start prompt and effective treatment.

PMID- 21176506
TI  - [Attitudes and actions of chronic obstructive pulmonary disease patients on
      treatment:a national multi-center investigative study].
AB  - OBJECTIVE: To investigate the attitudes and actions of patients with chronic
      obstructive pulmonary disease (COPD) on treatment. METHODS: A nation-wide multi
      center, questionnaire study was carried out to investigate the patient
      understanding and experience of COPD treatment between Sep. 2007 and Dec. 2008.
      The questionnaire included the patients' understanding of goal of COPD treatment,
      previous treatment, and expectation on drugs. The data were analyzed by
      descriptive statistical methods. RESULTS: 2072 patients with COPD in 11 centers
      were interviewed in the study. The final effective questionnaires were collected
      from 1698 cases. 653 patients had known of COPD. The attitudes and actions on
      treatment were analyzed based on these patients. The patients had different
      understanding of goals for COPD treatment, including 59.1% (384/650) for
      relieving symptoms. In recent 3 months, the most commonly used drugs were
      theophylline (53.7%, 351/653), iprotropium (39.8%, 260/653), tiotropium (27.1%,
      177/653). 72.0% (465/646) patients used the drugs according to the prescriptions.
      There were more than 80% patients who did not understand the side effects of anti
      cholinergics, beta-adrenergic agonists, inhaled steroids, inhaled steroid/long
      acting beta-agonist combination therapy, or theophyllines. 37.4% (240/641)
      patients were afraid of side effects of inhaled steroids. 42.2% (274/650)
      patients often took antibiotics. There was no oxygen supply at home in 60.1%
      (391/651) patients. 70.5% (457/648) did not have pulmonary rehabilitation.
      Requirement of long-term regular treatment was considered in 77.4% (500/646)
      patients. The most important thing about patients' attitude on ideal drugs for
      COPD was drug efficacy (79.6%, 481/604). The most ideal drug used in the past was
      fluticasone/salmeterol or tiotropium (16.9%, 78/461). CONCLUSIONS: Patients had
      different attitudes and actions on COPD treatment. Patient education should be
      strengthened to realize treatment goals for COPD.

PMID- 21176507
TI  - [Long-term outcome of bronchial artery embolization in the treatment of massive
      hemoptysis].
AB  - OBJECTIVE: To study the long-term outcome, safety, and complications of bronchial
      artery embolization (BAE) in the treatment of patients with massive hemoptysis.
      METHODS: A retrospective analysis of 232 cases of massive hemoptysis treated with
      BAE from February 2000 to February 2009 in our hospital was carried out. All
      cases were followed by repeated X-ray or CT examination, telephone calls, or
      questionnaires, with the longest period up to 9 years. RESULTS: There were 627
      blood vessels which were totally embolized by 741 coils for the 232 cases. The
      hemoptysis was stopped instantly in 100% of the patients. 91.8% (213/232) of the
      cases were cured and 19 cases (19/232, 8.18%) were improved. The overall
      effective rate was 100% (232/232). No serious or delayed complications occurred.
      None of the patients died. CONCLUSION: Bronchial artery embolization is effective
      in cases with massive hemoptysis for its immediate effect and safety.

PMID- 21176508
TI  - [A systematic review of the accuracy of diagnostic test of serum galactomannan
      antigen detection for invasive aspergillosis].
AB  - OBJECTIVE: To assess the value of galactomannan (GM) double-direct sandwich
      enzyme-linked immunosorbent assay (ELISA) in the diagnosis of invasive
      aspergillosis (IA). METHODS: A search in MEDLINE, EMbase, OVID, CBMdisc and CHKD
      from Jan. 1991 to Dec. 2008 was conducted to collect all articles about
      diagnostic tests of serum GM detection. Then the methodological quality was
      assessed by QUADAS-items, sources of heterogeneity investigated, pooled effect
      quantities evaluated, and meta-analysis studies, SROC curves, and subgroup
      analysis performed. RESULTS: Thirty-six articles with a population of 4959
      patients were included. The average prevalence of IA was 10%(532/4959). Our meta
      analysis reported a median heterogeneity (I(2) = 48.6%, P < 0.05), with a pooled
      DOR value of 19.10 (95%CI 12.67 - 28.79), a pooled sensitivity of 0.66 (95%CI
      0.61 - 0.70), a pooled specificity of 0.90 (95%CI 0.89 - 0.90), a pooled positive
      likelihood ratio of 5.48 (95%CI 4.27 - 7.02), a pooled negative likelihood ratio
      of 0.38 (95%CI 0.29 - 0.50), and an area under curve of SROC 0.88. The rate of
      underdiagnosis of serum GM detection was 34% (168/490) and the rate of
      misdiagnosis was 10% (466/4469). With a rise in the cut-off value the sensitivity
      of GM test decreased and specificity increased. Two consecutive positive tests
      decreased the sensitivity but increased the specificity. Age had no significant
      effect on the diagnosis by GM test. Both antifungal prophylaxis and antifungal
      therapy had no significant effect on sensitivity and specificity of GM test for
      IA diagnosis. CONCLUSION: Serum GM detection is an effective diagnostic tool for
      invasive aspergillosis in high-risk populations.

PMID- 21176509
TI  - [Hemodynamic effects of synchronous and asynchronous independent lung ventilation
      with different levels of positive end-expiratory pressure and tidal volumes on
      unilateral lung injury in dogs].
AB  - OBJECTIVE: To investigate the effects of asynchronous independent lung
      ventilation and synchronous independent lung ventilation with different levels of
      positive end-expiratory pressure (PEEP) and tidal volumes on hemodynamics and gas
      exchange in dogs with a hydrochloric acid induced acute lung injury. METHODS:
      Twelve dogs with hydrochloric acid induced acute lung injury (left lung) were
      ventilated with volume controlled ventilation (VCV). The animals were randomly
      divided by random digit table into 2 groups. The first group (group NS, n = 6)
      received asynchronous independent lung ventilation with the left lung PEEP 10 cm
      H2O (1 cm H2O = 0.098 kPa), VT 3.5 ml/kg and the right lung PEEP 0 cm H2O, VT 5
      ml/kg. The second group (group S, n = 6) received synchronous independent lung
      ventilation with the parameters as same as group NS. HR, mABP, mPAP, PAWP, CO and
      blood gas levels were measured during ventilation with different levels of PEEP
      (15, 20, 25 cm H2O) and VT (5, 7.5, 10 ml/kg) for 30 min. RESULTS: (1) After 30
      min ventilation, no significant differences for hemodynamics and gas exchange
      were found between group NS and group S when Left lung PEEP was 15 or 20 cm H2O
      and VT was 5 or 7.5 ml/kg. (2) After 30 min ventilation, HR, mABP, CO, PaO2/FiO2,
      SvO2 in group NS [(98 +/- 8) beats/min, (84 +/- 6) mm Hg (1 mm Hg = 0.133 kPa),
      (1.10 +/- 0.13) L/min, (199 +/- 14) mm Hg and (55 +/- 6)%, respectively] were
      significantly lower than those in group S [(124 +/- 9) beats/min, (103 +/- 7) mm
      Hg, (1.52 +/- 0.28) L/min, (221 +/- 15) mm Hg and (62 +/- 4)%, respectively] when
      PEEP was 25 cm H2O (all P < 0.01). (3) After 30 min ventilation, HR, mABP, CO,
      PaO2/FiO2, SvO2 in group NS [(92 +/- 6) beats/min, (83 +/- 9) mm Hg, (1.23 +/-
      0.08) L/min, (196 +/- 8) mm Hg and (57 +/- 2)%, respectively] were significantly
      lower than those in group S [(122 +/- 10) beats/min, (104 +/- 4) mm Hg, (1.56 +/-
      0.12) L/min, (216 +/- 14) mm Hg and (63 +/- 4)%, respectively] when VT was 10
      ml/kg (all P < 0.01). CONCLUSIONS: In this animal model, the hemodynamics kept
      stable when the difference between the left lung PEEP and the right lung PEEP was
      less than 20 cm H2O. Synchronous independent lung ventilation caused less
      hemodynamic compromise when higher PEEP (> 25 cm H2O) was used because of the
      marked asymmetry in the mechanics of the 2 lungs.

PMID- 21176510
TI  - [Correlation between the expression of perforin in T-lymphocyte subsets and
      antituberculosis in mice vaccinated with bacillus calmette-guerin].
AB  - OBJECTIVE: To investigate the relationship between the expression of perforin in
      T-lymphocyte subsets and antituberculosis in mice vaccinated with bacillus
      calmette-guerin (BCG). METHODS: 120 KM male mice were divided into a Control
      group (group C, n = 40, 20 each in group C1 or C2), a BCG vaccinated group (group
      B, n = 40, 20 each in group B1 or B2), a Tuberculosis group (TB group, n = 20),
      and a BT group, in which the mice were attacked by Mycobacterium tuberculosis
      H(37)Rv (MTB) after acquired immunity by vaccination with BCG (n = 20).
      Initially, mice in group B1, B2 and BT were vaccinated with BCG synchronously.
      Three month later, mice in group BT and TB were attacked by MTB synchronously.
      Samples of blood, lung, liver and spleen of mice in group C1 and B1 were
      collected at the same time. One month later again, Samples of blood, lung, liver
      and spleen of mice in group C2, B2, BT and TB were collected at the same time.
      Samples of blood were assayed for T-lymphocyte subsets expressing perforin
      (PFN(+)). The positive numbers of PFN(+) [CD(3)(+), CD(4)(+), CD(8)(+),
      CD(4)(+)CD(8)(+) double positive (CD(4)(+)CD(8)(+))] T lymphocytes and their
      percentages were assayed by flow cytometer. Specimens of lung, liver and spleen
      were examined for pathology and bacteriology. RESULTS: All the mice in the TB
      group acquired tuberculosis and the mortality was 55% (11/20) within 1 month.
      There were no tuberculosis and no death in mice of C, B and BT groups during the
      observation period. The amount of PFN(+) CD(8)(+) T lymphocytes in B group [(5.9
      +/- 0.9) * 10(3)] was significantly higher than that in C group [(4.8 +/- 0.8) *
      10(3)] (F = 42.24, P < 0.01). The PFN(+) CD(8)(+)% in TB group [(5.6 +/- 0.9)%]
      was significantly less than that in B group [(7.3 +/- 1.1)%] (F = 35.51, P <
      0.05). For Mice in the BT group, the amount of PFN(+) (CD(3)(+), CD(8)(+),
      CD(4)(+)CD(8)(+)) T lymphocytes [(20.1 +/- 5.5) * 10(3), (8.7 +/- 0.4) * 10(3),
      72 +/- 19] and their CD(3)(+)%, CD(8)(+)%, CD(4)(+)CD(8)(+)% [(23.3 +/- 3.3)%,
      (10.7 +/- 1.6)%, (0.084 +/- 0.015)%] were all higher than those in the B group
      [(13.0 +/- 3.2) * 10(3), (5.9 +/- 0.9) * 10(3), 36 +/- 5, (15.5 +/- 1.7)%, (7.3
      +/- 1.1)%, (0.044 +/- 0.007)%] or the C group [(11.1 +/- 3.0) * 10(3), (4.8 +/-
      0.8) * 10(3), 30 +/- 7, (14.9 +/- 1.7)%, (6.7 +/- 0.9)%, (0.040 +/- 0.006)%] or
      the TB group [(12.6 +/- 1.6) * 10(3), (5.0 +/- 0.1) * 10(3), 31 +/- 3, (14.0 +/-
      1.7)%, (5.6 +/- 0.9)%, (0.035 +/- 0.005)%] (F = 14.23 - 74.98, P < 0.01 or P <
      0.05), and the CD(4)(+)/CD(8)(+) in BT group (0.54 +/- 0.17) was significantly
      lower than that in C group (0.76 +/- 0.22) (F = 4.54, P < 0.01). CONCLUSIONS: Pre
      vaccination with BCG increased PFN(+) CD(8)(+) T lymphocytes in the host.
      Acquired immunity by BCG vaccination can protect the host from attack by
      Mycobacterium tuberculosis. Increased PFN(+) (CD(3)(+), CD(8)(+),
      CD(4)(+)CD(8)(+)) T lymphocytes may be involved. The expression level of PFN by T
      lymphocytes may be an important marker for antituberculosis immunity.

PMID- 21176511
TI  - [Cytokine production and clonal analysis of memory gammadelta T cells from
      patients with tuberculous pleurisy induced by bacille calmette guerin].
AB  - OBJECTIVE: To evaluate cytokine production and expression of gammadelta T cells
      within pleural fluid cells (PFCs) from patients with tuberculous pleurisy
      following bacille calmette guerin (BCG) stimulation. METHODS: PFCs were isolated
      from patients with tuberculous pleurisy, and assessed for cytokine production,
      cell subpopulation, phenotype and characterization of T cell receptors after
      stimulation with BCG. The positive PCR products were further labeled with
      fluorescence and analyzed by genescan technique to determine the CDR3 size and
      evaluate the clonality of the detectable TCR Vgamma and Vdelta T cells. RESULTS:
      Following stimulation with BCG, the positivity of interferon-gamma (IFN-gamma)
      producing CD(4) T cells and gammadelta T cells were 0.38% and 5.35%,
      respectively. Phenotypic analysis indicated that the majority of IFN
      gamma(+)gammadelta(+) T cells expressed CD(45RO)(+) (73.5%). In addition,
      delta(2) T cells produced IFN-gamma (11.1%) and TNF-alpha (25.5%). After
      expansion with BCG for 3 weeks, cells were harvested and mRNA extracted and RT
      PCR conducted to amplify cDNA with 3 primers for Vgamma and 8 primers for Vdelta.
      The results indicated that BCG selectively expanded delta(2) T cells with
      oligoclonal peak in Vdelta(2) cells. CONCLUSIONS: BCG induced memory gammadelta
      and delta(2) T cells to produce cytokines in PFCs. Genescan analysis showed that
      Vdelta(2) displayed oligoclonality.

PMID- 21176512
TI  - [CD(4)(+)T cells and immunological therapy of bronchial asthma].

PMID- 21176513
TI  - [The effect of dust storm on respiratory diseases and its mechanism].

PMID- 21176514
TI  - [Intensify the study of epidemiology focus on the evolution of influenza A
      virus].

PMID- 21176515
TI  - [Hygienic monitoring for disinfection by-products in drinking water].

PMID- 21176516
TI  - [Clinical features and prognosis of the mild cases of pandemic influenza H1N1
      virus infection].
AB  - OBJECTIVE: Analyze the clinical characteristics of the mild cases of pandemic
      influenza H1N1 virus infection, as well as the relationship of clinical
      characteristics and patient genders. METHODS: A total of 245 influenza A (H1N1)
      patients confirmed by viral nucleic acid detection were included in the study.
      The patients' personal information, signs and symptoms, lab and iconography data,
      disease course, negative seroconversion duration of new influenza A (H1N1) viral
      nucleic acid after antiviral treatment and hospitalization stay were analyzed.
      Measurement data were analyzed using one-way analysis of variance (ANOVA) by
      software SPSS 11.5. P < 0.05 was defined as statistically significant. RESULTS:
      (1) Among the 245 patients, 130 were males and 115 were females, yielding a sex
      ratio of 1.13:1. Almost 52.0% (127/245) of the patients came from Australia, and
      64.5% (158/245) were between 18 and 40 years old. (2) Clinical manifestations
      included fever (98.4%, 241/245), cough (80.8%, 198/245) and throat congestion
      (95.9%, 235/245), and lab findings were characterized by elevated C-reaction
      protein (CRP, 71.0%, 174/245) and neutrophil (52.2%, 128/245). (3) Female
      patients had significantly lower serum Prealbumin (pre-A) levels than male
      patients [(245.04 +/- 75.3) vs (273.34 +/- 92.18) mg/L, F = 5.55, P = 0.019]. (4)
      The patients' serum CRF levels significantly decreased after the treatment [(4.06
      +/- 3.47) vs (14.54 +/- 14.68) mg/L, F = 6.18, P = 0.016], while the levels of
      CD3, CD4 and CD8 were significantly increased after treatment [(1451.23 +/-
      443.97) vs (819.97 +/- 375.75) cell/ul, F = 32.61, P = 0.000; (771.33 +/- 251.92)
      vs (435.36 +/- 215.35) cell/ul, F = 44.43, P = 0.000; (593.16 +/- 237.19) vs
      (342.47 +/- 180.12) cell/ul, F = 28.518, P = 0.000, respectively]. (5)
      Approximately 30.6% (75/245) of the patients had abnormal signs on chest CT
      iconography, and 22.0% (54/245) had obvious signs indicating pneumonia. The
      average disease course was (3.9 +/- 1.2) days, the average hospitalization stay
      was (5.0 +/- 1.4) days, and the negative seroconversion duration of the mRNA
      after antiviral treatment was (3.8 +/- 1.4) days. CONCLUSION: The influenza A
      (H1N1) virus was characterized by fever, cough and throat congestion, with
      elevated CRP and neutrophil being the most significant lab findings. The
      influenza A (H1N1) strain was able to affect multiple organs, including being
      able to affect hepatic synthesis of pre-A as well as immune functioning. The
      influenza A (H1N1) influenza virus strain was mild clinically, with short disease
      course and good prognosis.

PMID- 21176517
TI  - [Analysis of adverse events following 2009 influenza A (H1N1) vaccinoprophylaxis
      in Beijing].
AB  - OBJECTIVE: To evaluate the safety of 2009 influenza A (H1N1) vaccine based on
      mass immunization initiative in Beijing. METHOD: There were 2 113 280 people were
      vaccinated during September to December 2009. The information of adverse events
      following immunization (AEFI) was collected through surveillance system, and
      descriptive methodology was used for data analysis. RESULTS: A Total of 612 AEFI
      cases were reported, among which there were 321 vaccine reaction cases following
      immunization, 203 coincidental illness cases, 82 psychogenic reaction cases, and
      6 pending cases. The rates of rare reactions and common reactions associated with
      vaccination were respectively 5.54/100 000 (117/2 113 280) and 9.65/100 000
      (204/2 113 280). The rate of serious rare reaction was 0.19/100 000 (4/2 113
      280). The rates of vaccine reactions in urban, suburb and county were 16.87/100
      000 (36/213 519), 17.81/100 000 (187/1 049 817) and 11.53/100 000 (98/849 944),
      respectively. The rates of rare reaction and common reaction in different age
      groups were between 3.65/100 000 (6/164 604) to 8.99/100 000 (27/300 176), and
      between 0.61/100 000 (1/164 604) to 22.06/100 000 (85/385 275). The 117 rear
      vaccine reaction cases were mainly allergic reaction (107 cases), and the 204
      common vaccine reaction cases were mainly fever (176 cases). There were 91.90%
      (295/321) vaccine reactions occurred within 24 hours of administration, and all
      cases had improved consequence. CONCLUSION: The mostly symptoms of AEFI cases
      during the period of 2009 influenza A (H1N1) vaccinoprophylaxis were anaphylaxis
      and fever. The types of adverse reactions and the level of serious events are
      consistent with the anticipation. There were no rear or new events occurred.

PMID- 21176518
TI  - [Phylogenetic analysis of hepatitis E virus strains isolated from both human and
      swine in Anqing City].
AB  - OBJECTIVE: To determine the genotype and phylogenetic characteristics of
      hepatitis E virus (HEV) strains isolated from the human and swine in Anqing City.
      METHODS: Twenty seven sera from sporadic hepatitis E patients and 400 commercial
      swine bile samples were collected in Anqing City. According to the collection
      time, the bile samples were equally divided into 4 groups which were named group
      A, B, C and D respectively. Nested reverse transcription polymerase chain
      reaction (RT-PCR) and DNA sequencing technology were performed to obtain the DNA
      sequences of HEV RNA Open Reading Frame 2 (ORF2) (150 nt) for all the serum and
      bile samples. The sample sequences and prototype sequences from the GenBank were
      aligned and their nucleotide sequence identities were calculated. A phylogenetic
      tree constructed according to the Bayesian inference method was used to analyze
      the genotype and phylogenetic relationship between the human and swine HEV
      strains isolated in Anqing City. RESULTS: The male-to-female sex ratio of the
      patients was 2.86:1 and the average age was 56.78 years old. Sixteen out of 27
      serum (59.26%) samples were HEV RNA positive. Human HEV strains isolated in
      Anqing City shared 74.75% - 82.99%, 75.26% - 83.64%, 72.77% - 80.57% and 88.03%
      91.63% nucleotide sequence identities with prototype I, II, III and IV HEV
      strains respectively. HEV RNA was detected in 22 out of 400 bile samples (5.5%).
      The swine HEV detection rates for group A, B, C and D were 7.00%, 3.00%, 9.00%
      and 3.00% respectively, showing no significant difference among these groups
      (chi(2) = 5.20, P = 0.16). Swine HEV strains isolated in Anqing City shared
      75.24% - 83.42%, 75.93% - 84.19%, 72.86% - 80.64% and 88.15% - 91.79% nucleotide
      sequence identities with prototype I, II, III and IV HEV strains respectively.
      Phylogenetic analysis revealed that all the HEV strains isolated from both the
      human and swine belonged to genotype IV and scattered in evolutionary branches
      without significant species aggregation. CONCLUSION: It's suggested that genotype
      IV HEV was the dominant genotype among the human and swine in Anqing City and
      probably transmitted between them in this area.

PMID- 21176519
TI  - [Formation and changes of regulated trihalomethanes and haloacetic acids in raw
      water of Yangtze River, Huangpu River and different treatment processes and
      pipelines network].
AB  - OBJECTIVES: To investigate the pollutant levels of regulated disinfection by
      products trihalomethanes (THMs) and haloacetic acids (HAAs) in raw water from the
      Huangpu River, the Yangtze River and different treatment processes and finished
      water, and to explore the changes tendency in transmission and distribution
      pipeline network. METHODS: A total of 65 ml water samples with two replicates
      were collected from different raw water, corresponding treatment processes,
      finished water and six national surveillance points in main network of
      transmission and distribution, water source for A water plant and B, C water
      plant was the Huangpu River and the Yangtze River, respectively. Regulated THMs
      and HAAs above water samples were detected by gas chromatography. RESULTS: The
      total trihalomethanes (THM(4)) concentration in different treatment processes of
      A water plant was ND-9.64 ug/L, dichlorobromomethane was the highest (6.43 ug/L).
      The THM(4) concentration in B and C water plant was ND to 38.06 ug/L,
      dibromochloromethane (12.24 ug/L) and bromoform (14.07 ug/L) were the highest in
      the B and the C water plant respectively. In addition to trichloroacetic acid in
      A water plant from the raw water, the other HAAs came from different treatment
      processes. The total haloacetic acids (HAA(6)) concentration of different treated
      processes in A water plant was 3.21 - 22.97 ug/L, mobromoacetic acid (10.40 ug/L)
      was the highest. Dibromoacetic acid was the highest both in B (8.25 ug/L) and C
      (8.84 ug/L) water plant, HAA(6) concentration was ND to 27.18 ug/L. The highest
      and the lowest concentration of THM(4) were found from the main distribution
      network of C and A water plant respectively, but the concentration of HAA(6) in
      the main water pipes network of A water plant was the highest, and the lowest in
      C water plant. The THMs concentration was 21.11 - 31.18 ug/L in C water plant and
      6.72 - 8.51 ug/L in A water plant. The concentration of HAA(6) was 25.02 - 37.31
      ug/L in A water plant and 18.69 - 23.32 ug/L in C water plant. The highest
      concentrations of brominated disinfection by-products in B and C water plant were
      54.57 ug/L and 45.38 ug/L respectively, those were higher than A water plant
      (18.98 ug/L), and higher than the chlorinated disinfection by-products in B and C
      water plants (30.23 ug/L and 30.60 ug/L). CONCLUSIONS: The THM(4) concentrations
      of finished water treated from Huangpu River was lower than finished water from
      the Yangtze River, while the HAAs concentrations in finish water from Huangpu
      River was higher than the two water plants of Yangtze River. The fluctuations of
      THMs and HAAs concentration in distribution network were low during transmission
      and distribution process.

PMID- 21176521
TI  - [Pregnancy weight gain and nutritional therapy on the outcome of gestational
      diabetes mellitus].
AB  - OBJECTIVE: To study the relationship of bodyweight gain and the occurrence of
      gestational diabetes mellitus (GDM) during pregnancy, and analyze the effect of
      the nutritional therapy on the outcome of GDM. METHODS: We collected 265 pregnant
      women who were diagnosed to be GDM and 571 pregnant women as the control group in
      the Xiamen Maternal and Child Health Hospital during 2007 - 2009. The general
      information of the subjects were collected. The bodyweight of the subjects were
      measured before the 20(th) week of pregnancy, 26 - 27(th) week (mid-gestation),
      35 - 36(th) week (late-gestation) of pregnancy and prior to delivery. The
      bodyweight gain of different pregnancy weeks of the two groups and the effect of
      bodyweight on GMD occurrence before 28(th) week of pregnancy were analyzed by
      ages (< 25, 25-, 30-, >= 35). Meanwhile, we prescribed the nutrition therapy to
      the GDM pregnant woman and the effect of the blood sugar control on the outcome
      of the pregnancy were evaluated. RESULTS: The bodyweight gain of 25-, 30-, older
      than 35 year-old subjects of the GDM group were (16.9 +/- 6.3), (16.8 +/- 6.1),
      (16.5 +/- 6.0) kg, respectively, the bodyweight gain of the control group were
      (13.9 +/- 3.0), (13.8 +/- 2.7), (13.3 +/- 2.7) kg (t = 6.259, 5.885, 3.533,
      respectively, all P values < 0.05). During the 20(th) to 27(th) week of the
      pregnancy, the bodyweight gain of the subjects younger than 25, 25-, 30-year-old
      in GDM group were (5.2 +/- 1.0), (5.4 +/- 1.7), (4.8 +/- 1.3) kg, respectively,
      the bodyweight gain of the control group were (3.3 +/- 1.3), (3.7 +/- 1.6) and
      (3.5 +/- 0.7) kg (t = 5.026, 9.659, 11.19, respectively, all P values < 0.05).
      During the period between 26(th) to 36(th) week, the bodyweight gain of subjects
      older than 35 year-old in GDP group was (3.6 +/- 2.0) kg which was less than the
      control group ((4.0 +/- 0.9) kg, t = -2.449, P < 0.05). 41.22% (54/131) and
      44.94% (40/89) of 25-, 30-year-old subjects in GDM group showed bodyweight gain
      more than 13 kg, but 30.04% (76/253) and 26.07% (55/211) in the control group (OR
      values were 1.633 and 2.315, both P values < 0.05). The rate of the abnormal
      birth weight of the GDM group with blood sugar controlled and the control group
      were 6.6% (12/182) and 9.4% (54/571) which was lower than the GDP group with
      blood sugar control failure (20.5% (17/83)) (chi(2) values were 11.460, 9.119,
      respectively, both P values < 0.0125). The rate of premature delivery was
      21.7%(18/83), higher than the control group (10.8%, 62/571) (chi(2) = 7.945, P <
      0.0125). The rate of the cesarean in the control group was 25.4%(145/571) which
      was lower than the two GDM groups, including the group which the blood sugar was
      well controlled (46.7%, 85/182) and not well controlled (65.0%, 54/83) (chi(2)
      values were 29.540, 53.860, respectively, both P values < 0.0125). CONCLUSION:
      The bodyweight gain in the mid-gestation could affect the occurrence of GDM. The
      bodyweight gain should be less than 13 kg before 28(th) week of the pregnancy
      whose age was 25-year-old. Nutritional therapy and blood sugar control in GDM
      pregnant women could improve the pregnancy outcome.

PMID- 21176520
TI  - [Determination of several herbicides, fungicides and estrogens in water from
      various treatment processes of different water plants in Shanghai by solid phase
      extraction-gas chromatography/mass spectrometry].
AB  - OBJECTIVE: To establish the solid phase extraction-gas chromatography/mass
      spectrometry (GC/MS) method for qualitative and quantitative determination of
      several herbicides, fungicides and estrogens in drinking water. METHODS:
      Duplicate 1 L water samples were collected from various treatment processes of
      different water plants. Target pollutants were extracted by XAD-2 resin from
      water samples and were eluted by 30% acetone-methanol. GC/MS was employed for
      qualitative and quantitative analysis of target pollutants. RESULTS: The linear
      ranges of standard curves of 6 target compounds including atrazine, alachlor, 4
      cumyphenol, thiabendazole, beta-estradiol and ethylestradiol were 0.1 - 10 ug/ml
      and the R(2) values were 0.9915 - 0.9995. The detection limits, the recovery
      rates, and the relative standard deviation (RSD) were separately 0.01 - 0.40
      ug/L, 74.0% - 112.0% and 2.3% - 14.8%. Atrazine (0.11 - 0.13 ug/L), 4-cumyphenol
      (0.20 - 0.35 ug/L), thiabendazole (0.92 - 1.46 ug/L), beta-estradiol (1.02 - 1.32
      ug/L) and ethylestradiol (0.96 - 1.66 ug/L)were all detected in raw water, post
      coagulation water, post-sedimentation water and finished water using Huangpu
      River as water source. Alachlor was not detected in any water samples in Huangpu
      River. The 6 target compounds were not detected in any water samples from the
      water plants using Yangtse River as water source. CONCLUSION: The methods with
      high sensitivity and satisfying selectivity are suitable to simultaneously
      qualitative and quantitative determination of target pollutants in drinking
      water. Concentrations of above-mentioned pollutants in drinking water coming from
      Huangpu River are obviously higher than in drinking water coming from Yangtze
      River. Thiabendazole, beta-estradiol and ethylestradiol at the level of ug/L
      exist in drinking water coming from Huangpu River and more attention should be
      paid to surveillance of future.

PMID- 21176522
TI  - [Relationship between duration of low to moderate intensity physical activity and
      the prevalence of metabolic syndrome].
AB  - OBJECTIVE: To analyze the relationship between low to moderate physical activity
      and the prevalence of metabolic syndrome (MS). METHODS: A multi-stage stratified
      cluster sampling was conducted in 31 provinces, autonomous regions, and
      municipalities in the interior of China according to the program of the National
      Nutrition and Health Survey in 2002. Questionnaire survey, interview, physical
      examination, measurement of biochemical indices and dietary investigation were
      done. In total, the physical activity of 26 477 persons aged 18 or above were
      investigated. The duration of low to moderate physical activity was divided into
      five grades: 0-min/week, 90-min/week, 151-min/week, 301-min/week, over 420
      min/week, and the MS prevalence were investigated respectively. The relationship
      between MS and age (including four age groups 18-, 35-, 45-, 60 or above) or the
      duration of physical time were investigated. RESULTS: The MS prevalence among
      persons aged 18 or above was 9.4% (2490/26 477). And the prevalence was 10.3%
      (1191/11 516) in man and 8.7%(1299/14 961) in women, respectively (chi(2) =
      21.035, P = 0.000). The MS prevalence was 2.1% (127/6070) in 18-years old group
      and 15.0% (1012/6734) in over 60 years old group. The MS prevalence increased
      with increasing age (chi(2) = 776.768, P = 0.000). 81.2% (21 499/26 477) of
      subjects engaged in low to moderate intensity physical activity. The percentage
      of spending time on physical activity over 420 min/week was dominant and as high
      as 43.7% (11 561/26 477). The MS prevalence was 13.8% (166/1203) for 0-min grade,
      13.2% (64/485) for 90-min grade, 11.8% (153/1298) for 151-min grade, 10.1%
      (124/1225) for 301-min grade and 12.5% (512/4090) for over 420 min grade (chi(2)
      = 9.58, P = 0.047). Logistic regression analysis results showed, the MS risk of
      subjects spending 301-min per week on low to moderate intensity physical activity
      was significantly low than the MS prevalence among subjects of 90-min grade, OR =
      0.844 (95%CI: 0.675 - 0.968), and no statistical difference was found in people
      spending over 420 min per week OR = 0.936(95%CI: 0.769 - 1.136). CONCLUSION: Most
      of people aged 18 or above engaged in low to moderate intensity physical
      activity. MS prevalence may be decreased by low to moderate intensity physical
      activity for 301-min per week, but the decrease was not significant while the
      duration of time was longer than 420 min per week.

PMID- 21176523
TI  - [The main nutrients digestibility of genetically modified rice and parental rice
      in the terminal ileum of pigs].
AB  - OBJECTIVE: To compare the digestibility of main nutrients in genetically modified
      rice with double antisense starch-branching enzyme gene and parental rice.
      METHODS: Seven Wuzhishan healthy adult barrows were surgically fitted with a T
      cannula at the terminal ileum. After surgery, seven pigs were randomly divided
      into two groups, and fed genetically modified rice and parental rice by a
      crossover model. Ileal digesta were collected for analysis of main nutrient
      digestibility. RESULTS: The apparent digestibility levels of protein in
      genetically modified rice and parental rice were 69.50% +/- 4.50%, 69.61% +/-
      8.40%, respectively (t = 0.01, P = 0.994); true digestibility levels of protein
      were 87.55% +/- 4.95%, 87.64% +/- 9.40%, respectively (t = 0.01, P = 0.994); fat
      digestibility levels were 72.86% +/- 0.34%, 77.89% +/- 13.09%, respectively (t =
      0.95, P = 0.378); carbohydrate digestibility levels were 72.92% +/- 7.43%, 92.35%
      +/- 5.88%, respectively (t = 4.27, P = 0.005). The apparent and true
      digestibility of 17 amino acids had no significant difference in the two rice.
      CONCLUSION: Carbohydrate digestibility in genetically modified rice was
      significantly lower than that in non-genetically modified rice, other main
      nutrients digestibility in the two rice have substantial equivalence.

PMID- 21176524
TI  - [Study on the cellular and humoral immunity effect of recombinant Chinese hamster
      ovary cell hepatitis B vaccine in adults].
AB  - OBJECTIVE: To evaluate the cellular and humoral immunity effect of 10 ug and 20
      ug recombinant Chinese hamster ovary (CHO) cell hepatitis B vaccine in adults by
      randomized double-blind controlled trials. METHOD: A total of 642 adults aged 18 
      45 years old, non-vaccinated against hepatitis B, and hepatitis B five blood
      indicators negative were selected as the study subjects. The study subjects were
      randomly divided into two groups and each group had 321 subjects. The subjects
      were given 10 ug and 20 ug recombinant CHO hepatitis B vaccination respectively
      by 0, 1st, 6th month schedule. Blood sample was collected from each study subject
      one month after the second dose vaccination. The anti-HBs level was detected by
      Abbott chemiluminescence detection method (I2000) to evaluate humoral immunity
      status. Of all the study objects, 153 cases were randomly selected by the Excel
      random function. Their blood samples were collected and Lymphocyte were separated
      to detect the IL-4 and IFN-gamma levels in vitro by enzyme-linked immunospot
      (ELISPOT) method to evaluate the cellular immunity status. RESULTS: The anti-HBs
      seroconversion rates in 10 ug and 20 ug dose group were 88.8% (285/321) and 95.3%
      (306/321) respectively, and 95%CI were 85.4% - 92.2% and 93.0% - 97.6%
      respectively. The spot forming cell (SFC) of IL-4 of the 20 ug-dose group (x(-) =
      20.31) were significantly higher than the 10 ug-dose group (x(-) = 8.19, t =
      3.27, P < 0.01). With the increasing of anti-HBs titer, the SFC of IL-4 also went
      up significantly. There was a positive correlation between SFC of IL-4 and anti
      HBs (Spearman correlation coefficient = 0.538, P < 0.0001). No significant
      difference was found for IFN-gamma SFC in two groups (10 ug group: x(-) = 1.49;
      20 ug group: x(-) = 0.86; t = 1.83, P > 0.05). CONCLUSION: The humoral and
      cellular immune effects of 20 ug recombinant CHO hepatitis B vaccine are better
      than that of the 10 ug recombinant CHO hepatitis B vaccine.20 ug recombinant CHO
      hepatitis B vaccine should be chosen as the adult's hepatitis B prevention
      vaccine.

PMID- 21176525
TI  - [In vitro studies on the growth and proliferation characteristics of rat bone
      mesenchymal stem cells].
AB  - OBJECTIVE: This study was to investigate the growth and proliferation
      characteristics of rat bone mesenchymal stem cells (BMSCs) isolated by the method
      of whole bone marrow culture and to explore the effect of cell inoculation
      density and incubation period on cell proliferation, with an aim to provide
      multipotential seed cells for preventing from degenerative disease. METHODS: Bone
      mesenchymal stem cells were isolated by the method of whole bone marrow culture
      and then cultured in vitro. The cell morphologic features were observed by
      inverted microscope. The cell surface antigens were identified by flow cytometry.
      The effect of cell inoculation density and culture period on cell growth and
      proliferation was explored by analyzing the characteristics of a ten-day cell
      growth curve in 96-well plates. RESULTS: Flow cytometry results showed the
      detection rates for CD29, CD34 and CD45 were 97.68% (7607/7788), 7.93% (661/8340)
      and 2.76% (215/7788) respectively, which was consistent with the expression
      characteristics of BMSCs surface antigens. BMSCs became uniform after three cell
      passages, existing in a typical shape of whirlpool or radial colony. The
      senescent cells started to appear at 7(th) passage, and more senescent cells were
      found at 10(th) passage. The growth curve for moderate inoculation density was
      typically S-shaped. Lag phase was found during the first two days, and logarithm
      growth phase was in the following three days. Plateau phase started from the
      6(th) day and cell numbers decreased slightly from the 8(th) day. CONCLUSION: The
      whole bone marrow culture is an effective way to obtain BMSCs. A moderate
      inoculation density was more advantageous to cell proliferation, by which more
      seed cells could be obtained.

PMID- 21176526
TI  - [Study on an intervention model of "schools without infected students with
      schistosoma japonica" in heavy endemic areas].
AB  - OBJECTIVE: To study an intervention model of "schools without infected students
      with schistosoma japonica", to control and prevent students from schistosoma
      infection. METHODS: Twelve primary schools of four heavy endemic counties
      (districts) with schistosomiasis in the Poyang Lake areas were selected as the
      study fields, of which, ten schools were the experimental groups, and the other
      two schools were the control groups by cluster random sampling. All enrolment
      students were the target population. The baseline survey was carried out in 2005,
      and an intervention model, "information dissemination + behavior participation +
      behavior encouragement", was applied in the experiment groups in 2006 - 2008,
      then the effect of intervention was assessed. RESULTS: Before intervention
      (2005), the anti-schistosomiasis knowledge awareness rate of experimental and
      control groups were 14.75% (324/2196) and 16.58% (91/549), and the different was
      not significant (chi(2) = 1.14, P > 0.05); the rate of accurate attitude of anti
      schistosomiasis were 14.71% (323/2196) and 11.84% (65/549) in experimental and
      control groups, and the difference was not significant (chi(2) = 2.98, P > 0.05);
      the rate of contacting infected water were 15.44% (18 988/122 976) and 15.03%
      (4622/30 744) in experimental and control group and the difference was not
      significant (chi(2) = 3.13, P > 0.05); and the infection rate of schistosomiasis
      of experiment control groups were 9.65% (212/2196) and 10.56% (58/549), the
      difference was not significant (chi(2) = 0.41, P > 0.05). After one year
      intervention (2006), the anti-schistosomiasis knowledge awareness rate of
      experimental and control groups were 97.79% (2032/2078) and 18.11% (98/541), and
      the different was significant (chi(2) = 1794.31, P < 0.01); the rate of accurate
      attitude of anti-schistosomiasis were 99.09% (2059/2078) and 13.49% (73/541) in
      experimental and control group, and the difference was significant (chi(2) =
      2077.45, P < 0.01). After 1 - 3 years intervention (2006 - 2008), there were no
      any contactors with infected water and infectors with schistosome in students of
      the experiment group in successive 3 years. While in the control group of the
      same period, the rate contacting infected water were 16.12% (4884/30 296), 11.11%
      (3079/27 720) and 12.25% (3451/28 168); the infection rate of schistosomiasis
      were 8.87% (48/541), 7.47% (37/495) and 7.95% (40/503), respectively. CONCLUSION:
      The intervention model of health promotion, "information dissemination + behavior
      participation + behavior encouragement", can effectively control and prevent
      students from infecting schistosoma japonica in heavy endemic areas with
      schistosomiasis.

PMID- 21176527
TI  - [New views on endometrial intraepithelial neoplasia].

PMID- 21176528
TI  - [Quality requirements of cultured cell lines for scientific research].

PMID- 21176529
TI  - [Evaluation of two-tier grading system and significance of p53 protein over
      expression in ovarian serous carcinoma].
AB  - OBJECTIVE: To evaluate the two-tier MDACC grading system for ovarian serous
      carcinoma by comparing with the WHO grading system, and to investigate the role
      of p53 immunostaining in ovarian serous carcinoma grading. METHODS: 72 cases
      ovarian serous carcinoma of ovary were graded basing on the MDACC and WHO grading
      systems, respectively. Statistic analyses were made for the relationship between
      the data obtained from two grading systems and their clinical significance. All
      the cases were examined immunohistochemically by using antibody against p53
      protein and the immunohistochemistry findings were analyzed with the two grading
      systems and clinical parameters. RESULTS: There was a good correlation between
      the MDACC and WHO grading system (r=0.543, P=0.000). Neither system has a
      definite relationship with the disease-free survival time (P=0.170 vs. P=0.075),
      cytoreduction (P=0.478 vs. P=0.120), and the curative effect of platinum-based
      chemotherapy (P=0.418 vs. P=0.403). However, compared with the WHO grading
      system, MDACC grading system has a better correlation with tumor stage (P=0.041
      vs. P=0.002), 3-year disease-free survival rate (P=0.077 vs. P=0.004), overall
      survival time (P=0.080 vs. P=0.046), and p53 immunohistochemistry results
      (P=0.334 vs. P=0.035). No significant difference was found between p53
      immunohistochemistry results with other clinical characteristics and prognostic
      factors. CONCLUSIONS: Compared with the WHO system, the MDACC system showed a
      better prognostic value and was more likely correlated with the novel dualistic
      model for ovarian serous carcinogenesis. Although p53 immunostaining was valuable
      in assisting MDACC grading, it should be cautious to use it alone as an
      independent indicator in predicting the prognosis of ovarian serous carcinoma.

PMID- 21176530
TI  - [Clinicopathologic study of juvenile granulosa cell tumor of ovary].
AB  - OBJECTIVE: To study the clinicopathologic features, diagnostic criteria and
      prognostic parameters of juvenile granulosa cell tumor of ovary. METHODS: The
      clinical and pathologic findings of 7 cases of juvenile granulosa cell tumor were
      retrospectively reviewed. Immunohistochemical study was carried out in 6 of these
      cases. The follow-up data were also analyzed. RESULTS: The mean age of the
      patients was 24 years (range=6 to 53 years). Four patients presented with
      hormonal disturbance, while 3 patients presented with abdominal pain or swelling.
      Six patients underwent unilateral salpingo-oophorectomy. Six cases were in stage
      IA and the remaining case in stage IC. Follow-up information was available in 6
      patients and the duration of follow up ranged from 1 to 10 years (mean=4.3
      years). Five patients remained healthy, with no evidence of tumor recurrence. One
      patient died of tumor metastasis one year after the diagnosis. Gross examination
      showed that the tumor masses ranged from 7 to 20 cm in the greatest dimension
      (average=13.4 cm). Four of the 7 tumors were mixed solid-cystic in appearance and
      2 cases were unilocular cystic in nature. Microscopic examination showed diffuse
      atypical follicular structures formed by granulosa cells. The granulosa cells
      contained round hyperchromatic nuclei, without nuclear grooves or Call-Exner body
      formation (6/7). In one of the cases studied, minor foci resembling adult
      granulosa cell tumor were also demonstrated. The degree of cellular atypia varied
      (3 cases with severe atypia, 1 case with moderate atypia and 3 cases with mild
      atypia). The mitotic count ranged from 1 to more than 5 per 10 high-power fields.
      Immunohistochemical study showed diffuse positivity for vimentin (6/6). The
      staining for cytokeratin (AE1/AE3) and calretinin was negative. Four cases
      expressed CD99 and 1 case was positive for inhibin. CONCLUSIONS: Juvenile
      granulosa cell tumor is characterized by the presence of diffuse atypical
      follicular structures formed by small round cells, without nuclear grooves or
      Call-Exner bodies. Rare cases contain minor foci of adult granulosa cell tumor.
      They can be unilocular cystic in nature. The degree of nuclear atypia, mitotic
      activity and size of the tumor vary and do not correlate with the risk of
      recurrence and aggressive biologic behavior.

PMID- 21176531
TI  - [Clinicopathologic and prognostic significance of serum levels of cytokines in
      patients with advanced serous ovarian cancer prior to surgery].
AB  - OBJECTIVE: To study the clinicopathologic and prognostic significance of serum
      levels of six cytokines (IFN-gamma, TNF-alpha, IL-10, IL-5, IL-4, IL-2) in
      patients with advanced serous ovarian cancer prior to surgery. METHODS: The serum
      levels of six cytokines were detected in 51 patients with advanced serous ovarian
      cancer and 46 healthy controls, using cytometric bead arrays. RESULTS: The serum
      levels of IFN-gamma (20.68+/-11.45), IL-2 (4.54+/-1.18), IL-4 (5.66+/-2.25), IL-5
      (2.72+/-0.86) ug/L and IL-10 (5.93+/-7.92) ug/L were higher (P<0.01, P<0.05) and
      the serum level of TNF-alpha (7.53+/-8.47) was lower (P<0.01) in patients with
      advanced serous ovarian cancer than those in the healthy controls. The IFN
      gamma/IL-4 ratio (3.93+/-2.34) of the patients was lower than that of the
      controls (P<0.01). Kaplan-Meier analysis revealed that patient's age (P=0.016),
      menopausal status (P=0.001) and serum IL-10 level (P=0.010) correlated
      significantly with patient's survival. Cox regression analysis showed that serum
      IL-2 (P=0.045) and IL-10 levels (P=0.007) were the independent prognostic
      factors. CONCLUSIONS: Patients with advanced serous ovarian cancer have Th1/Th2
      imbalance and immune function disturbance. The age of patients and menopausal
      status are important prognostic factors. IL-2 and IL-10 level are also
      independent predictors of survival.

PMID- 21176532
TI  - [Clinicopathologic study on 61 cases of uterine papillary serous carcinoma with
      or without adjuvant therapy].
AB  - OBJECTIVE: To study the clinicopathologic features of uterine papillary serous
      carcinoma (UPSC) and the roles of adjuvant therapy. METHODS: Sixty-one cases of
      UPSC with operation done and followed up for a period of 4 to 9 years were
      enrolled into the study. The histology of slides specimens were reviewed and
      immunohistochemical study was performed. The follow-up and survival data were
      analyzed. RESULTS: All of the 61 patients were post-menopausal, with a median age
      of 68 years. The clinical presentations included abnormal vaginal bleeding,
      abdominal symptoms and abnormal Pap smears. The median size of the tumors was 7.5
      cm (range=1.2 to 14.8 cm). There were 27.9% cases in FIGO stage I (8.2% in stage
      IA, 14.8% in stage IB and 4.9% in stage IC), 9.8% in stage II, 32.8% in stage III
      and 29.5% in FIGO stage IV. The histologic features were similar to those of the
      ovarian counterpart, with tumor cells containing the high-grade nuclei and
      arranged in complex papillae. Psammoma bodies were identified in 24.6% of the
      cases. Immunohistochemical study showed that the tumor cells demonstrated diffuse
      and strong nuclear staining for p53 and Ki-67. They were negative for estrogen
      receptor and progesterone receptor. Fifteen of the 61 cases (24.6%) showed no
      evidence of myometrial invasion. However, ten of the 15 cases had extrauterine
      disease, with peritoneal (6/15) and nodal (9/15) involvement. Tumors with deep
      myometrial invasion, lymphovascular permeation and nodal metastasis were
      associated with worse prognosis by univariate analysis. Fifty-six patients
      received adjuvant therapy. The number of patients receiving adjuvant chemotherapy
      alone, adjuvant radiotherapy alone and combined adjuvant
      chemotherapy/radiotherapy were 42, 24 and 10, respectively. The median survivals
      of the chemotherapy group and non-chemotherapy group (with or without
      radiotherapy) were 66.4 months and 32.8 months, respectively. CONCLUSIONS: UPSC
      has distinctive clinical and pathologic features. The tumor stage, lymph node
      status, lymphovascular permeation and depth of myometrial invasion were important
      prognostic factors. Adjuvant chemotherapy for stage III/IV tumors or recurrent
      UPSC may have survival benefit.

PMID- 21176533
TI  - [Expression of human papillomavirus type 16/18 in human cervical carcinomas by
      the quantum dot fluorescent in-situ hybridization].
AB  - OBJECTIVE: To investigate fluorescence in situ hybridization labeled with quantum
      dots (QDs) for the detection of human papillomavirus 16/18 (HPV16/18) infection
      in cervical carcinoma patients. METHODS: A total of 80 biopsy samples of squamous
      carcinoma of cervix were assayed for HPV 16/18 infection by using quantum dot
      labeled fluorescent in situ hybridization (QD-FISH) and chromogenic in situ
      hybridization (CISH) techniques, respectively. The results obtained by using two
      different methods were statistically analyzed. RESULTS: The positive rate for
      HPV16/18 by QD-FISH was 88.8% (71/80), higher than that (80.0%) by CISH, however,
      the result was statistically not significant (P=0.127). The positive detection
      rates for HPV16/18 by using both methods increased coincidentally with raising of
      the tumor grading stage. CONCLUSION: The sensitivity and specificity of HPV
      infection detectable by QD-FISH is higher than that by the CISH technique.

PMID- 21176534
TI  - [Granulomatous lobular mastitis: a clinicopathologic study of 68 cases].
AB  - OBJECTIVE: To study the clinical and pathologic features of granulomatous lobular
      mastitis (GLM). METHODS: Sixty-eight cases of GLM were retrieved from the
      archival file. The clinical data and histologic features were retrospectively
      reviewed. RESULTS: Sixty-eight patients presented with breast mass. Ulceration in
      overlying breast skin was seen in 9 cases. Most of the patients had history of
      breast feeding. None of them had evidence of specific infections involving the
      breast. The clinical and radiologic features mimicked malignancy. Histologically,
      GLM was characterized by the presence of non-necrotizing granulomas, usually
      admixed with neutrophils and associated with benign ductolobular units. The
      ductolobular architecture was still preserved. The duration of follow up ranged
      from 6 to 36 months. Four patients suffered from disease recurrence. CONCLUSIONS:
      GLM shows clinical and radiologic features reminiscent of breast cancer. Correct
      diagnosis requires histologic examination of the biopsy specimens.

PMID- 21176535
TI  - [Correlation of polymorphism of Nme1-1465 T>C and TGFbeta1-509 T>C with genetic
      susceptibility of gastric carcinoma].
AB  - OBJECTIVE: To explore the correlation of functional genetic variants in Nme1-509
      C>T and TGFbeta1-1465 T>C genes to the genetic susceptibility of gastric
      carcinoma in Fujian province, China. METHODS: A case-control study was conducted
      in a population in Fujian province. The polymorphism of TGFbeta1-509 C>T
      (rs1800469), Nme1-1465 T>C (rs16949649) in 273 gastric carcinoma patients and 277
      cancer-free controls, frequency-matched by age and sex, were analysed by using
      Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry
      (MALDI-TOF-MS). Adjusted odds ratios (OR) and 95% confidence evaluation intervals
      (95%CI) measured by multivariate Logistic regression analysis were adopted in
      studying the correlation of the gene polymorphism with the susceptibility of
      gastric cancer. RESULTS: After the adjustment using Logistic regression or the
      potential confounding effects of gender and age, as compared with TT+CT genotype
      gastric carcinoma patients, the homozygous Nme1-1465CC genotype carriers had a
      significantly higher risk in lymph node metastasis, with the OR of 2.5 (95%CI
      0.08-2.10; P=0.029). There was no association obtained between TGFbeta1-509 T>C
      genotype with the tumor size, cell differentiation, tumor invasion and lymph node
      metastasis in gastric carcinoma. In the intestinal type gastric carcinoma group,
      when compared with the wild homozygous Nme1 TT* TGFbeta1 CC, Nme1 TC* TGFbeta1
      TC, Nme1 TC* TGFbeta1 TT and Nme1 CC* TGFbeta1 TC genotype carriers, there was a
      significantly decrease of risk in gastric carcinogenesis of 0.42 fold (95%CI 0.54
      0.94, P=0.022), 0.32 fold (95%CI 0.42-0.97, P=0.013) and 0.26 fold (95%CI 0.42
      0.97, P=0.008), respectively. CONCLUSIONS: There is a significant relationship
      between polymorphism of Nme1-1465 T>C and the prognosis of carcinoma of stomach.
      It also demonstrates that coexistence of Nme1-1465 T>C and TGFbeta1-509 T>C genes
      may provide a synergistic effect of increasing the susceptibility of gastric
      carcinogenesis.

PMID- 21176536
TI  - [Effects of azidothymidine on p33ING1b expression, apoptosis and senescence of
      TJ905 human glioblastoma cell line].
AB  - OBJECTIVES: To investigate the pharmacological effects of azidothymidine (AZT) on
      p33ING1b expression, senescence and apoptosis of TJ905 glioblastoma cells.
      METHODS: TJ905 cells were treated with AZT at a serial concentrations of 50, 100
      and 200 umol/L. Semi-quantitative RT-PCR and cytochemical staining of senescence
      related-galactosidase (sbeta-Gal) were used to evaluate the expression of
      p33ING1b mRNA and to label the senescent cells at the 1st, 3rd and 6th
      generations, respectively. In situ cell death detection and single cell gel
      electrophoresis were used to detect the apoptosis at the 3rd and 6th generations.
      RESULTS: AZT induced the expression of p33ING1b mRNA and senescence of the tumor
      cells of the 1st generation in a dosage and time dependent manner. At the 6th
      generation, the relative amount of p33ING1b RT-PCR product (1.44+/-0.23) and
      sbeta-Gal labeling index of 200 umol/L group (45.62+/-6.74) were significantly
      higher than those of the 1st (0.95+/-0.13 and 7.82+/-2.40) and the 3rd generation
      cells (1.35+/-0.23, 26.27+/-7.17) of the same group, and cells of the same
      generation in the 50 umol/L (0.85+/-0.24, 27.37+/-6.41) and 100 umol/L groups
      (1.23+/-0.34, 35.49+/-5.12, P<0.01). There was a significant positive correlation
      between the p33ING1b mRNA expression and the labeling index of sbeta-Gal. Pro
      apoptotic effects of AZT became obvious at the 6th generation. CONCLUSION: AZT
      upregulates the expression of p33ING1b, a possible mechanism in regulating
      senescence and apoptosis of the TJ905 cells.

PMID- 21176537
TI  - [Expression of BCSG1-siRNA in tumor transplants of human breast cancer cell line
      in nude mice].
AB  - OBJECTIVE: To investigate the inhibitory effects of siRNA targeting BCSG1 gene
      expression in tumor transplants of human breast cancer cell line in nude mice.
      METHODS: Four-pairs of small interfering RNA sequences of BCSG1 were chemically
      synthesized and inserted into the plasmid expression vectors, and were then
      transfected into human breast carcinoma cell line MCF7 by liposome method.
      Plasmid vector with unrelated sequence was used as the vector control. Cells
      transfected with 4 siRNA sequences, control vector and naive FCF7 cells were
      transplanted into the nude mice. The tumor inhibition was analysised.
      Immunohistochemical SP method and semi-quantitative RT-PCR were adopted to detect
      the BCSG1 mRNA and protein expression, respectively. Breast tissue samples of
      human infiltrating ductal carcinoma, ductal hyperplasia and fibroadenoma were
      also used as the controls. RESULTS: The inhibition rates of tumor growth in four
      BCSG1-siRNA transfected groups were remarkably higher than those of the vector
      control group and naive MCF7 cells (P<0.01). Compared with that of the vector
      control and naive MCF7 cell group, there was a significant decrease of BCSG-1
      protein expression in the four experimental groups by immuno-histochemistry
      staining (P<0.01). In addition, BCSG1 mRNA expression in the four groups
      transfected with BCSG1-siRNA were significantly less than that of the control
      vector group, naive MCF7 cell control group and human breast IDC (P<0.01).
      CONCLUSION: BCSG1-siRNA down-regulates the expression of BCSG1 and inhibits
      effectively growth of the transplaned human breast cancer cell line in nude mice.

PMID- 21176538
TI  - [The influence of fluoride on expression of OPGL and M-CSF genes and their
      proteins in rats with experimental fluorosis and the therapeutic effect of Danlan
      Xianpeng Liaofu caspule].
AB  - OBJECTIVE: To investigate mRNA and protein expressions of OPGL and M-CSF mRNA in
      bones of rats with experimental fluorosis induced by intake of fluoride in the
      drinking water, and to study the antagonizing effects of Danlan Xianpeng Liaofu
      capsules on the gene expression. METHODS: Totally 72 SD rats were randomly
      assorted into 6 groups including the control group, the fluoride group, the high
      dosage (0.8 g/kg*d), mid-dosage (0.4 g/kg*d) and low dosage (0.2 g/kg*d)
      medication groups and the borax group (borax, 0.8 g/kg*d). The distribution of
      female and male rats in each group was divided up on a fifty-fifty basis. Except
      the control group, a NaF containing water (NaF 50 mg/L in concentration) was
      supplied as the drinking water for all the experimental rats in order to
      establish experimental fluorosis. The thickness and density of trabecula and the
      thickness of bone cortex were measured by light microscopy. The fluoride content
      in urine and bone were analyzed by using fluoride ion selective electrode method.
      Expressions of OPGL and M-CSF mRNA and protein were studied using RT-PCR and
      immuno-histochemistry, respectively. RESULTS: (1) 10/12 of the experimental
      fluorosis rats developed dental fluorosis, and 2/12 of dental fluorosis rats
      occurred in the low-dosage medication group. Fluoride content in urine and bone
      of the fluorosis rats increased (P<0.05). (2) Compared with that of the control
      rats, the bone trabecular depth, cortical thickness and trabecular density in
      experimental fluorosis rats were remarkably reduced. (3) Compared with that of
      the control group, mRNA expression of both OPGL and M-CSF was increased in the
      fluoride group rats. The difference was statistically significant (P<0.05). (4)
      Compared with that of the fluoride group animals, the expression intensity of
      OPGL mRNA decreased in animals of the control group, the high, mid- and low-
      dosage medication groups and the borax group. Among them, except the low-dosage
      group, the difference between all the other groups and the fluoride group was
      statistically significant, respectively (P<0.05). There was also a decrease of M
      CSF mRNA in all the 3 medication groups and the borax group animals in comparing
      with that of the fluoride group and the difference was also statistically
      significant (P<0.05), respectively. (5) Compared with that of the control group.
      There were an increase of OPGL and a decrease of M-CSF protein expression; and in
      addition, there were a decrease of OPGL and an increase of M-CSF protein
      expression in all 3 medication groups and the borax group in comparing with that
      of the fluoride group anima (P < 0.05). CONCLUSIONS: Excessive fluoride induces
      an accelerated bone turnover and may promote the absorption activity of
      osteoclasts by increasing the expression of OPGL and M-CSF. Danlan Xianpeng
      Liaofu capsule may be capable of regulating bone remodeling through a down
      regulation on OPGL and M-CSF expression.

PMID- 21176539
TI  - [Clinicopathologic features of nasal heterotopic neuroglial and meningeal
      encephalocele].

PMID- 21176540
TI  - [Association of expression of antigen processing machinery components with HLA-I
      in cervical lesions].

PMID- 21176541
TI  - [Application of combined single-cell suspension in quality control of
      immunohistochemistry].

PMID- 21176542
TI  - [Ovarian endometrioid carcinoma with sexcord-like structures: report of two
      cases].

PMID- 21176544
TI  - [Epithelioid schwannoma: report of a case].

PMID- 21176543
TI  - [Recurrent follicular dendritic cell sarcoma in abdomen: report of a case].

PMID- 21176545
TI  - [Primary liver carcinosarcoma: report of a case].

PMID- 21176546
TI  - [Nodal and ovarian matastases in leiomyosaromas of uterus: report of a case].

PMID- 21176547
TI  - [Calcifying fibrous pseudotumor of the chest: report of a case].

PMID- 21176548
TI  - [Recent advances in enteropathy-associated T-cell lymphoma].

PMID- 21176549
TI  - [Clinical significance of the revised international federation of gynecology and
      obstetrics staging system 2009].

PMID- 21176550
TI  - [Explanations and discussions of the revised international federation of
      gynecology and obstetrics staging system 2009].

PMID- 21176551
TI  - [Antenatal diagnosis of Down's syndrome].

PMID- 21176552
TI  - [Clinical analysis about the management and the perinatal outcomes of pregnancy
      with chronic myeloid leukemia].
AB  - OBJECTIVE: to investigate the perinatal outcomes of pregnancy with chronic
      myeloid leukemia (CML) and how to manage it during pregnancy. METHODS: to
      retrospectively analyse the clinical datas about the perinatal outcome and the
      obstetric management of the 16 cases of pregnancy with CML during the last 30
      years in a single center. RESULTS: (1) management ang perinatal outcomes: among
      the 16 pregnancies nine ended with therapeutic abortion during the first or
      second trimester and no CML complications were observed. The average gestation
      week was 7 weeks (5 - 13 weeks) when they came to our hospital. Seven pregnancies
      gave birth, among which CML was diagnosed during pregnancy in four patients and
      pregnancy was confirmed during CML in three patients. The average gestation week
      was 36 weeks (27 - 40 weeks(+2)) when they came to our hospital. Among the seven
      women three were treated with hydroxyurea (one became pregnant while she was on
      hydroxyurea and she elected to continue her pregnancy and continued to use
      hydroxyurea), one with leukapheresis twice after her 40 weeks of gestation, one
      with plateletpheresis and three hadn't any treatment. In the seven pregnacies
      three developed severe pre-eclampsias, including the two had hydroxyurea during
      the gestation. The average delivery gestational week was 38 weeks (33 weeks(+4) -
      41 weeks), two were premature birth. Two caesarean sections, three vaginal
      deliveries and two forceps deliveries. There were two postpartum hemorrhage,
      during the 24 hours the amount of bleeding was 1500 - 1800 ml and secondary
      disseminated intravascular coagulation happened. Seven patients gave birth to
      seven infants whose average birth weight was 2469 g (1820 - 2810 g), of whom two
      were premature infants, two low birth weight infants, one had congenital
      malformation and two had abnormal blood routine examinations. (2) Management
      after delivery and prognosis: during the nine patients who ended pregnancy with
      therapeutic abortion during the first or second trimester four withdraw, one died
      whose course of disease was 3 years and the other four were alive during 5 months
      to 72 months, among which one had stem cell transplantation, two are taking
      imatinib mesylate and one takes hydroxyurea. Among the seven patients who
      deliveried two withdraw, two died and three are alive. Among the seven infants
      two withdraw, the other five have normal development following 4 months to 9
      years. CONCLUSIONS: CML patient may have successful pregnancy and delivery, and
      it is not the absolute indication for terminating pregnancy. On the other hand,
      CML and the treatment during pregnancy can have side effect on the mother and the
      fetus, so the patients should be monitored and treated in tertiary hospitals.

PMID- 21176553
TI  - [Clinical outcomes and characteristics of concurrent eclampsia and hemolysis,
      elevated liver enzymes, and low platelets syndrome].
AB  - OBJECTIVE: the purpose was to describe the outcomes and characteristics of the
      obstetric patients with concurrent eclampsia and hemolysis, elevated liver
      enzymes, and low platelets syndrome (HELLP) syndrome. METHODS: we retrospectively
      collected the materials between December 1999 and December 2008 in Obstetric
      Critical Care Center of Guangzhou. There were 76 patients in rolled then they
      were divided into two groups according to with or without HELLP syndrome. All the
      patients were injected Magnesium Sulfate to control seizure and to prevent the
      recurring of seizure. We analyzed the characteristics (such as age, gestational
      weeks, blood pressure after seizure), complications, biochemistry markers, the
      rate for intensive care unit (ICU) admittion, the need for mechanical
      ventilation, the Glasgow coma score (GCS) when admitted into ICU, computed
      tomography scan (CT) or magnetic resonance imaging (MRI), death rate of maternal
      and others, then compared between the two groups. RESULTS: (1) general data:
      There were 17 patients admitted with both eclampsia and HELLP syndrome, and 59
      patients admitted eclampsia without HELLP syndrome. The incidence of eclampsia
      with HELLP syndrome was 22% (17/76). In eclampsia with HELLP syndrome group, the
      systolic blood pressure was higher and the rate of preterm also was higher [(182
      +/- 20) mm Hg (1 mm Hg = 0.133 kPa) vs. (159 +/- 21) mm Hg, P < 0.05]. But in
      regard to the age, gestational weeks, the rate of regular prenatal care and
      diastolic blood pressure, there were no differences between the two groups. (2)
      Biochemistry markers: the aspartate transaminase (AST), lanine transaminase
      (ALT), blood urea nitrogen and creatinine were significantly increased in
      eclampsia with HELLP syndrome group than eclampsia without HELLP syndrome group
      [(879 +/- 337) U/L vs. (90 +/- 27) U/L, (344 +/- 83) U/L vs. (43 +/- 11)U/L,
      (2245 +/- 294) U/L vs. (485 +/- 61) U/L, (14 +/- 9) mmol/L vs. (7 +/- 3) mmol/L,
      (140 +/- 92) umol/L vs. (83 +/- 28) umol/L, P < 0.01, P < 0.05], and the platelet
      was lower in eclampsia with HELLP syndrome group [(38 +/- 13) * 10(9)/L vs (172
      +/- 46) * 10(9)/L, P < 0.01]. (3) Clinical outcomes: The maternal death rate was
      35% (6/17) in eclampsia with HELLP syndrome patients, and significantly higher
      than the rate in eclampsia without HELLP syndrome group (3%, 2/59) (P < 0.05).
      There were more patients admitted to ICU and more patients who need mechanical
      ventilation in eclampsia with HELLP syndrome (13/17 vs. 34%, 9/17 vs. 24/, P <
      0.05), also more patients with GCS <= 8 in eclampsia with HELLP syndrome when
      admitted to ICU (8/17 vs. 7/59, P < 0.05), compared to the eclampsia without
      HELLP syndrome group. There were more patients complicated with cerebral venous
      thrombosis and cerebral hemorrhage in eclampsia with HELLP syndrome group than
      other group (8/17 vs. 7%, P < 0.05). Five of six patients died of cerebral
      hemorrhage in eclampsia with HELLP syndrome group, while other two missing cases
      in eclampsia without HELLP syndrome group all died of cerebral hemorrhage. The
      all missing cases were performed CT or MRI and seven (7/8) of them showed
      cerebral hemorrhage. CONCLUSION: the incidence of concurrent eclampsia and HELLP
      syndrome was not rare, it happened seriously and with more mortalities, such as
      cerebral hemorrhage, and also the maternal mortality rate was significantly
      higher. It should be warning that the obstetrician should take great attention
      for these women, and consider life support treatment for them.

PMID- 21176554
TI  - [Prenatal diagnose of abnormalities of fetal limb bone].
AB  - OBJECTIVE: to discuss the prenatal diagnosis of abnormalities of fetal limb bone.
      METHODS: we selected 18 cases which long bone of fetus less than 2SD of average
      volume of gestational weeks or long bone changed into angle or other fetus's
      abnormalities by first B-mode ultrasonic. All above cases was delivered at
      Capital Medical University of Obstetric and Gynecological Hospital during Jan.
      2006 to Dec. 2009. We B-mode ultrasonic was used to measure fetus's biparietal
      diameter (BPD), femur length (FL), abdominal circumference (AC), head
      circumference (HC), humerus length (HL), amniotic fluid index (AFI) and
      structures of organ and calculated FL/AC, growth speed of long bone. The standard
      of achondroplasia is that FL and HL are less than 4SD of average of gestational
      weeks or FL/AC less than 0.16. The standard of Osteogenesis Imperfecta is fetal
      long bone of fetus shows short and thick, curves into angle, fracture in uterus
      by X-ray, or skull shows thin or sink by X-ray. RESULTS: (1) by B-mode ultrasonic
      and X-ray exam of all 18 cases: 7 cases shows that HC > 2SD, 10 cases shows too
      much amniotic fluid, 12 cases shows AFI > 18.0, 9 cases shows abnormalities of
      narrow cavitas thoracis, disordered vertebral column, or unusual architecture of
      heart. For cases 1 to 14 are achondroplasia, among which, 11 cases are FL < 4SD
      and HL < 4SD, 2 cases are FL < 3SD and HL < 4SD, 1 case is not only FL < 2SD and
      HL < 3SD but also hydroncus all over the body of fetus. The growth velocity of
      long bone of fetus in all the 14 cases is more slowly than the normal rate. For
      all the above 14 cases, 12 cases FL/AC < 0.16, 1 case FL/AC = 0.19, 1 case FL/AC
      = 0.20. The length of femur or humerus is shorter than the normal rate and have
      other abnormalities the above last two cases. For case 15 and 16, they don't show
      any abnormalities of bone growth though one year's follow up studying. For case
      17 and 18, they are osteogenesis imperfecta. (2) The result of fetal perinatal
      period fate and autopsy: there are 8 female and 10 male in all the 18 cases. One
      case is labored after 39 weeks pregnancy, and it is low birth weight infant,
      weight < 3%th. All the other cases are normally birth weight infant. All the 18
      cases of abnormalities of fetal limb bone are examined by chromosomes check,
      among which, 9 cases are amniocentesis, 7 cases are cordocentesis, 2 cases are
      checked chromosomes by fetus cord blood, all the caryotype are normal. In the 16
      autopsy cases, 14 cases are achondroplasia or hypochondroplasis. It can be seen
      amplifying extremities, hyperplasia chondrocytes of tubiform born, karyomegaly,
      anachromasis, hyperplasia capillaries though microscope and grow up into
      cartilage irregularly. Also can be seen hyperplasia chondrocytes of epiphyses,
      delaying osteosis. 2 cases are osteogenesis imperfecta. It can be seen broadening
      of metaphyses, exility of bone trabeculae. For the other two cases which the
      fetus is alive, we do the follow up studying to their one year old one of them is
      low birth weight new born, their limb and height are all normal. CONCLUSIONS: to
      diagnose fetal Achondroplasia, it is not only based on the significantly shorter
      of femur or humerus length but also based on the dynamics observing the long bone
      growth velocity and calculating FL/AC. For osteogenesis imperfecta fetus, it
      should be diagnosed by fractures in uterus though X-ray.

PMID- 21176555
TI  - [Study on apoptosis of placental syncytiotrophoblast in patients with severe
      preeclampsia].
AB  - OBJECTIVE: to investigate apoptosis of placental syncytiotrophoblast in patients
      with early-onset and late-onset severe preeclampsia. METHODS: from November 2008
      to May 2009, 15 cases with early-onset severe preeclampsia and 15 cases with late
      onset severe preeclampsia matched with 10 women with normal pregnancies as
      control at Sixth Affiliated Hospital of Shanghai Jiaotong University were
      enrolled in this study. Enzyme-linked immunosorbent assay was used to measure
      syncytiotrophoblast microparticles (STBM) levels in peripheral venous plasma.
      Caspase-3 were measured by western blotting. RESULTS: (1) STBM: the level of STBM
      of (71 +/- 21) microg/L in early-onset group were significantly higher than (42
      +/- 30) microg/L in late-onset group and (26 +/- 11) microg/L in control group (P
      < 0.05). The level of STBM in late-onset group and control group did not reach
      statistical difference (P > 0.05). (2) Caspase-3: the level of caspase-3 protein
      were 0.85 +/- 0.61 in early-onset group and 0.77 +/- 0.46 in late-onset group,
      which were all significantly higher than 0.32 +/- 0.15 in control group (P <
      0.05). However, the level of caspase-3 protein in early-onset group did not show
      remarkable difference compared with that in late-onset group (P > 0.05).
      CONCLUSION: STBM are shed into the maternal circulation in higher amounts in
      early-onset preeclampsia, which indicated that early-onset and late-onset severe
      preeclampsia may have different etiology and pathogenesis.

PMID- 21176556
TI  - [Multicenter randomized controlled clinical study on levornidazole and sodium
      chloride injection in the treatment of pelvic anaerobic infections].
AB  - OBJECTIVE: to evaluate clinical efficacy and safety of levornidazole in the
      treatment of pelvic anaerobic infections. METHODS: a multicenter randomized
      controlled clinical study was conducted to evaluate clinical efficacy and safety
      of levornidazole. One hundred and fourty-three patients with pelvic anaerobic
      bacteria infection were classified into 70 cases treated by levornidazole in
      study group and 73 cases treated by Ornidazole in control group. Those patients
      in two groups were both administered at a dose of 0.5 g twice daily for 5 - 7
      days. The rate of clinical efficacy, bacteria clearance and adverse effect were
      recorded and compared between two groups. RESULTS: at the endpoint, the rate of
      clinical efficacy were 80% (56/70) in study group and 81% (59/73) in control
      group, which did not reach significant difference (P > 0.05). The rate of
      bacteria clearance were 97% (36/37) in study group and 92% (22/24) in control
      group, which also did not reach significant difference (P > 0.05). The rate of
      adverse reaction of 3% (20/70) in study group was significantly lower than 22%
      (16/73) in control group (P < 0.05). CONCLUSION: it is effective and safe to
      treat pelvic anaerobic infections with levornidazole and sodium chloride
      injection.

PMID- 21176557
TI  - [Analysis of high risk factors associated with cervical intraepithelial neoplasia
      in married women aged 25 - 54 years in Beijing between 2007 - 2008].
AB  - OBJECTIVE: to investigate high risk factors associated with cervical
      intraepithelial neoplasia (CIN) in married women aged 25 to 54 years in Beijing.
      METHODS: from Mar. 2007 to Sep. 2008, 6339 married women at age of 25 to 54 years
      were selected randomly by cross sectional survey in a total of 137 communities of
      12 districts or counties in Beijing. The interview was carried out with unified
      questionnaires, gynecological examination. The cervical smear cytology and high
      risk human papillomavirus (HR-HPV) infection of cervical secretion were detected.
      Women with abnormal cervical cytology underwent colposcopy and cervical biopsy.
      Odd ratio (OR) and 95% confidence interval (CI) of related high risk factors with
      CIN were studied by logistic regression analysis. RESULTS: among 6339 women, the
      prevalence rate of CIN including 4 squamous cell carcinoma (SCC) was 5.90%
      (374/6339). By multinomial regression analysis, HR-HPV infection (95%CI: 9.953 -
      15.811), History of trichomonas vaginitis (95%CI: 1.046 - 2.104), oral
      contraceptives (95%CI: 1.087 - 1.806), age less than 45 years old (95%CI: 1.069 -
      1.828) were related with CIN. CONCLUSION: infection rate of HR-HPV is an
      independent risk factor of CIN, however, the history of trichomonas vaginitis,
      oral contraceptives and age less than 45 years old are related risk factors of
      CIN.

PMID- 21176558
TI  - [Relationship between ultrastructural features with the expression of connexin 43
      in the uterine junction zone and pathogenesis of adenomyosis].
AB  - OBJECTIVE: to investigate the relationship between the ultrastructural features
      combined with the expression of connexin (Cx43) protein in uterine junction zone
      and pathogenesis of adenomyosis. METHODS: from Nov. 2008 to Nov. 2009, 30
      patients with adenomyosis (including 14 cases with proliferative endometrium and
      16 cases with secretory endometrium) as study group matched with 30 women with
      cervical intraepithelial neoplasia (CIN) III treated by hysterectomy as control
      group were enrolled in this study in Affiliated Hospital to Inner Mongolia
      Medical College. The expression of Cx43 in uterine junction zone of patients with
      adenomyosis was detected by immunohistochemisty staining. The ultrastucture of
      eutopic endometrium, uterine junction zone and outer 1/3 myometrium in both
      groups without history of dilatation and curettage, C-section and uterine surgery
      were observed by using transmission electron microscopy. RESULTS: (1) the
      expression of Cx43 in proliferative and secretroy uterine junction zone were
      0.133 +/- 0.018 and 0.137 +/- 0.021 in study group and 0.154 +/- 0.016 and 0.141
      +/- 0.018 in control group, which reached statistical difference (P < 0.05).
      However, it didn't show significant expression of Cx43 between proliferative and
      secretory uterine junction zone in study or control group (P > 0.05). The
      expression of Cx43 in proliferative and secretory of eutopic endometrium of 0.067
      +/- 0.017 and 0.062 +/- 0142 in study group were significantly lower than 0.094
      +/- 0.005 and 0.080 +/- 0.005 in control group. It didn't show statistical
      difference of Cx43 expression between proliferative and secretroy eutopic
      endometrium in both group. The expression Cx43 in outer myometrium of
      proliferative phase were 0.184 +/- 0.022 in study group and 0.188 +/- 0.028 in
      control group, which did not show significant difference (P > 0.05). It also did
      not exhibit statistical difference of Cx43 expression in outer myometrium of
      secretory phase (0.178 +/- 0.022, 0.191 +/- 0.025, P > 0.05). (2) Morphological
      changes: the area of uterine smooth muscle cells of the uterine junction zone of
      (24.3 +/- 1.6) microm(2) in study group were significantly increased than (21.8
      +/- 2.0) microm(2) in control group (P < 0.01). The length of the cell membrane
      dense plaques of (1.07 +/- 0.17) microm in study group was significantly
      increased than (0.71 +/- 0.07) microm in control group (P < 0.01). The myocytes
      exhibited cellular hypertrophy and disordered arrangement and fewer caveolae.
      There was cylindrical and dentate, chromatin margination, more heterochromatin in
      which muscle cells of nuclear surface of the uterine junction zone. Less
      cytoplasmic myofilaments and more intermediate filaments. Mitochondria were
      increased, the volume increased significantly vacuolization. The rough
      endoplasmic reticulum and Golgi apparatus were more prominent. Otherewise, mast
      cells and fibroblasts were close and glandular epithelial cells showed desmosome
      connection which villus thickening and dense. All features were more prominent at
      the junctional zone. CONCLUSIONS: the down-regulation of Cx43 expression and
      ultrastructure changes in the junction zone might play an important role in
      pathogenesis of adenomyosis.

PMID- 21176559
TI  - [Extracellular signal-regulated protein kinase activation in endometrium with
      polycystic ovary syndrome and its significance].
AB  - OBJECTIVE: to investigate the activation of mitogen-activated protein kinase
      (MAPK)/extracellular signal-regulated protein kinase (ERK) signaling pathway in
      the endometrium of women with polycystic ovary syndrome (PCOS) and its effect and
      significance in the cause of hyperplasia and carcinoma; and investigate the
      factors which affect the activation of the MAPK/ERK signaling pathway. METHODS:
      collected 52 patients diagnosed as PCOS who were taken dilation and curettage of
      uterus as study, while 32 non-PCOS patients matched as control group. Serum
      hormonal parameters, fasting blood glucose and insulin were measured in all
      patients. The PCOS patients were sub-group as insulin resistance group and non
      insulin resistance group; all the patients were carried out pathology inspection
      of endometria, and the PCOS patients were sub-group as endometrial hyperplasia
      and carcinoma group and normal endometrium group based on the outcome of
      pathology inspection. Western blot were performed to detect the expressions of
      ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2), the activation of ERK1/2. RESULTS:
      (1) the expression of p-ERK1/2 [(61 +/- 13)%] in the endometrium in PCOS group
      was higher than that in the control [(44 +/- 10)%, P < 0.01]. (2) The expression
      of p-ERK1/2 was significantly increased in group of endometrial hyperplasia and
      carcinoma [(70 +/- 11)%] compared to that in group of normal endometrium [(55 +/-
      10)%, P < 0.01], while there were significant difference between group of insulin
      resistance [(63 +/- 13)%] and group of non-insulin resistance [(55 +/- 7)%, P <
      0.01]. (3)Fasting insulin level, insulin area under the curve and body mass index
      were related to the expression of p-ERK1/2 in endometrium with PCOS, the
      correlation coefficient were 0.447, 0.456 and 0.381, respectively (all P < 0.01).
      CONCLUSIONS: the MAPK/ERK signaling pathway in endometrium with PCOS was
      overactivation, which was related to the endometrial hyperplasia and carcinoma;
      while the activation of MAPK/ERK signaling pathway were effected by insulin
      resistance and hyperinsulinemia.

PMID- 21176560
TI  - [Expression and its clinical significance of hsa-miR-155 in serum of endometrial
      cancer].
AB  - OBJECTIVE: to investigate the expression of the hsa-miR-155 in serum of
      endometrial cancer and its clinical significance. METHODS: collected 44 cases
      blood specimens before surgery operation from Sep. 2008 to Dec. 2009, and
      collected 12 cases blood specimens from the health of volunteers in comparison.
      Real time quantity PCR was used to detect the expression of hsa-miR-155 in those
      specimens and analyzed clinical pathological with the expression of hsa-mir-155
      in endometrial cancer. RESULTS: the expression of hsa-miR-155 was (3.9 +/- 0.7)
      in endometrial cancer, which was significantly higher than that in control group
      (P < 0.01). The expressions of hsa-miR-155 were (3.7 +/- 0.6), (3.9 +/- 0.6) and
      (3.7 +/- 0.6) times in well, moderately and poorly differentiated endometrial
      cancer, respectively, while there were not significant difference (P > 0.05). The
      expressions were (3.8 +/- 0.6) and (3.9 +/- 0.6) times between endometrioid
      adenocarcinoma and non-endometrioid adenocarcinoma, and there were significant
      difference (P > 0.05). The expressions were (2.1 +/- 0.4) and (5.6 +/- 0.8) times
      in stage I - II and III - IV endometrial cancer, respectively, in which there
      were significant difference (P < 0.05). The expressions of hsa-miR-155 were (5.5
      +/- 0.5) and (1.9 +/- 0.2) times between lymph node metastasis and without lymph
      node metastasis in endometrial cancer, in which there were significant difference
      (P < 0.01). CONCLUSION: Hsa-miR-155 may play an important role in the
      proliferation, and metastasis of endometrial cancer, which may be a indicator in
      the diagnosis and prognosis of endometrial cancer and may be used as a predictive
      biomarker.

PMID- 21176561
TI  - [Effect of hypotensive fluid resuscitation on microcirculation in an uncontrolled
      hemorrhagic shock of pregnant rabbits].
AB  - OBJECTIVE: to study the effects of hypotensive resuscitation on microvascular
      perfusion in a clinically relevant model of uncontrolled hemorrhagic shock in
      pregnancy. METHODS: thirty New Zealand white rabbits at 15 - 25 days, pregnanal
      age were randomly divided into three groups; Group normal saline traditional
      aggressive resuscitation (NS), traditional aggressive resuscitation in the
      prehospital phase with a large quantity of normal saline and Ringer's solution to
      maintain mean arterial pressure (MAP) at the approximately 80 mm Hg (1 mm Hg =
      0.133 kPa) level: Group normal saline hypotensive resuscitation (NH) and group
      hypertonic hyperosmotic hypotension resuscitation (HHH), hypotensive
      resuscitation in the prehospital phase with a bolus dose of 4 ml/kg normal saline
      or hypertonic hydroxyl ethyl starch (10% hydroxyl ethyl starch +7.5% NaCl),
      followed by Ringer's solution to maintain MAP at 60 mm Hg. Production pregnant
      rabbit model with hemorrhagic shock. The experiment consisted of four
      phases:basic phase (0 miniutes), shock phase (0 - 30 miniutes), prehospital phase
      (30 - 90 miniutes) and hospital phase (90 - 180 miniutes). MEASUREMENTS: (1)
      arteriole and venule diameter were continuously monitored by microcirculatory
      detecting instrument; (2) functional capillary density (FCD) of each phase was
      expressed by the percentage of opening capillaries segments relative to basic
      phase; (3) blood pH, BE PCO(2), PO(2) in pregnant rabbits were determined with a
      Medica Easy Blood Gas Analyzer. RESULTS: (1) there were no significant
      differences among three groups in arteriole and venule diameter at baseline (P >
      0.05). After hemorrhagic shock arteriole diameter were NS (50.8 +/- 5.6) um, NH
      (47.6 +/- 3.7) um, HHH (51.3 +/- 2.4) um, respectively, with no significant
      differences between groups (P > 0.05). At the end of prehospital resuscitation
      phase and hospital resuscitation phase, significant differences were found in
      arteriole diameter in group NS (52.8 +/- 4.9, 56.0 +/- 3.8) um, NH (61.3 +/- 2.9,
      65.4 +/- 3.2)um and HHH group (67.0 +/- 4.1, 74.1 +/- 4.8) um (P < 0.05); after
      hemorrhagic shock venule diameter were NS (79.6 +/- 7.0) um, NH (75.3 +/- 5.3) um
      and HHH (76.2 +/- 5.8) um, respectively, with no significant differences between
      groups (P > 0.05). At the end of prehospital resuscitation phase and hospital
      resuscitation phase, venule diameter were NS (81.1 +/- 6.7, 84.4 +/- 6.0) um, NH
      (82.8 +/- 3.3, 85.4 +/- 4.3) um and HHH (86.9 +/- 5.8, 89.4 +/- 6.8) um,
      respectively, with no significant differences between groups (P > 0.05). (2) The
      values of FCD in every groups were all 100%. After hemorrhagic shock FCD were NS
      (39.8 +/- 6.8)%, NH (43.9 +/- 4.0)%, HHH (44.0 +/- 4.8)%, respectively, with no
      significant differences between groups (P > 0.05); at the end of prehospital
      resuscitation phase and hospital resuscitation phase, FCD were NS (54.5 +/- 7.3,
      59.7 +/- 4.8)%, NH (63.1 +/- 5.8, 70.3 +/- 5.6)% and HHH (80.5 +/- 6.9, 91.7 +/-
      4.7)%, respectively, with significant differences between groups (P < 0.05). (3)
      Blood gas parameter: the values of blood pH, BE, PO(2), PCO(2) in pregnant
      rabbits in all groups were within normal bounds at basic phase. Shock phase
      induced typical hyperventilation in all groups, with increase of arterial PO(2)
      and decrease of PCO(2); at the end of hospital resuscitation phase, there were no
      significant difference among the three groups in the values of blood PCO(2) (P >
      0.05); the values of blood PO(2) at the hospital resuscitation phase were
      significantly lower in NS groups than corresponding values in the other groups (P
      < 0.05). After hemorrhagic shock there was significant metabolic acidosis as
      shown by decrease of pH, BE; at prehospital resucitation phase, pH, BE values
      tended to increase in all the groups but not reach to base period. At the end of
      hospital resucitation phase. The pH, BE value was significantly higher in NS
      group than those in the other two groups (P < 0.05). (4) Median survival time in
      NS (2.1 +/- 0.2) days group was significantly shorter than NH (3.0 +/- 0.3) days
      and HHH (3.6 +/- 0.3) days group (P < 0.05). FCD at the end of the hospital
      resuscitation were significantly related with survival time (r = 0.655, P =
      0.000). CONCLUSION: compared with traditional aggressive fluid resuscitation,
      hypotensive resuscitation reduce constriction of arterial and venule diameter,
      increase FCD, alleviate metabolic acidosis and improve long-term survival.
      Hypertonic hydroxyl ethyl starch resuscitation ameliorate microcirculation
      without improving survival rate.

PMID- 21176562
TI  - [Synergism of antitumor effects on ovarian carcinoma using autocatalytic caspase
      3 combined with flavopiridol].
AB  - OBJECTIVE: to investigate the antitumor effects on ovarian cancer using
      recombinant adenoviruses expressing autocatalytic caspase-3 driven by amplified
      human telomerase reverse transcriptase promoter (AdHTVP2G5-rev-casp3) combined
      with flavopiridol. METHODS: following the treatment with AdHTVP2G5-rev-casp3
      combined with flavopiridol, cell survival rate was measured by cell counting kit
      8; cell apoptotic rate and cell cycle distribution were detected by flow
      cytometry. Western blot was performed to observe the expression of p17, the
      active subunit of caspase-3, and p85, the cleavage segment of substrate of
      caspase-3, in AO cells. The mice survival rates were measured for abdominally
      metastatic tumor models and the volume of tumor nodules were determined for
      subcutaneous tumor models following the treatments of AdHTVP2G5-rev-casp3
      combined with flavopiridol. HE staining was used to detect the histopathological
      changes of various organs, and the serum level of alanine transaminase (ALT) and
      aspartate aminotransferase (AST) were measured to monitor liver damages following
      the intraperitoneal administration of AdHTVP2G5-rev-casp3 and flavopiridol.
      RESULTS: there was no significant cell-killing effects or apoptosis in AO cells
      following treatments with AdHTVP2G5-rev-casp3 or flavopiridol at low dosage alone
      (apoptotic rate all < 11%), whereas significant synergism of their sequential
      combination was observed in AO cells. This sequential treatment of AdHTVP2G5-rev
      casp3 [multiplicity of infection (MOI) was 20] infection for 72 hours, followed
      by flavopiridol (300 nmol/L) for 48 hours, could result in the most substantial
      cell death, and AO cells survival rate and apoptotic rate were 73.5% and 11.6%,
      respectively. Following treatments with AdHTVP2G5-rev-casp3 at low doses (MOI =
      10), there was a significant increase in cell number with S-phase content
      (62.5%), which resulted in the most marked apoptosis induced by sequential
      treatments with flavopiridol. The sequential combination could induce
      significantly higher levels of p17 and p85 expression than that when their
      applications alone. Combined AdHTVP2G5-rev-casp3 and flavopiridol treatment
      prolonged mouse survival [mean survival time of (286 +/- 6) days] and suppressed
      tumor growth significantly (tumor growth suppression rate of 81%), when compared
      with treatment using either alone. The levels of serum ALT and AST were not
      significantly elevated and no obvious lesions were found in any organs in
      treatments with AdHTVP2G5-rev-casp3 of low doses combined with flavopiridol.
      CONCLUSIONS: AdHTVP2G5-rev-casp3 at low doses results in a significant increase
      in cell number with S-phase content, which significantly enhanced the sensitivity
      of cells to flavopiridol. Treatments of autocatalytic caspase-3 combined at low
      doses with flavopiridol result in significant synergistic antitumor effects,
      significant tumor growth suppression and prolonged survival of mice. When
      compared with normal dose flavopiridol alone, the combination could resulted in
      minimal liver toxicity.

PMID- 21176564
TI  - [Perspectives of audiology construction].

PMID- 21176565
TI  - [China's current situation and future tasks in hearing implant].

PMID- 21176563
TI  - [Potential role of ezrin and its related microRNA in ovarian cancer invasion and
      metastasis].
AB  - OBJECTIVE: to screen microRNA (miRNA) that inhibit expression of the metastasis
      related gene ezrin in ovarian cancer cells and explore their correlation to the
      invasion and metastasis of ovarian cancer. METHODS: the differential expression
      of ezrin in two paired high-metastatic and low-metastatic cell lines were
      examined by real time reverse transcription (RT)-PCR and western blot. A
      functional screen with microarray was employed to identify miRNA that were
      differentially expressed between SKOV3 and SKOV3ip cell lines. Three programs,
      TARGETSCAN (http://www.targetscan.org), MICROCOSM (http://www.ebi.ac.uk/enright
      srv/microcosm/htdocs/targets/v5/) and PICTAR (http://www.pictar.mdc-berlin.de),
      were employed to identify all miRNA, which may inhibit the expression of ezrin
      and were differentially expressed between SKOV3 and SKOV3ip cells. To test the
      repressive potential of these miRNA, synthetic mimetics were transfected
      individually into SKOV3ip cells and endogenous ezrin expression levels monitored
      by western blot and real-time RT-PCR. RESULTS: (1) the mRNA average level of
      ezrin were (81.74 +/- 5.34)-fold higher expression level in SKOV3ip versus SKOV3
      cells (P < 0.01), while (2.61 +/- 0.14)-fold in HO-8910PM versus HO-8910 cells (P
      < 0.01). Elevated protein level of ezrin were observed in SKOV3ip cells compared
      with that in SKOV3 cells, and the same that in HO-8910PM cells compared with HO
      8910 cells. Paired SKOV3 and SKOV3ip cells were employed to study the more
      significant difference in ezrin expression between them. (2) By a functional
      screen using miRNA microarray combined with bioinformatics analysis, the miR-183
      and miR-22 were indentified as two candidate miRNA, which may have the potential
      regulatory role in ezrin expression. Real time RT-PCR assays revealed that miR
      183 and miR-22 were, respectively, an average of (5.84 +/- 0.66)-fold and (6.67
      +/- 0.67)-fold higher expression level in SKOV3ip versus SKOV3 cells (P < 0.01),
      which were in agreement with the microarray data. A subsequent validation by
      western blot and real time RT-PCR revealed that over-expression of miR-183 and
      miR-22 could both lead to an obvious decrease in ezrin protein level, while there
      were not signicant difference in the level of ezrin mRNA (P > 0.05). CONCLUSION:
      increased expression of miR-183 and miR-22 may both repress the protein level of
      ezrin, indicating that miR-183 and miR-22 may bear a potential role in inhibiting
      ovarian cancer metastasis in a ezrin-mediated way.

PMID- 21176566
TI  - [To emphasize the outcome assessment in children with cochlear implant].

PMID- 21176567
TI  - [Minimal access surgery for cochlear implant].

PMID- 21176568
TI  - [Treating sudden deafness by intravenous injecting Alprostadil leads to acute
      ache of lower limbs: tow cases report].

PMID- 21176569
TI  - [Updates of bone anchored hearing aid].

PMID- 21176570
TI  - [Feasibility analysis and surgical highlight of cochlear implantation in infants
      under 12 months of age].
AB  - OBJECTIVE: To explore feasibility and surgical highlight of cochlear implantation
      in infants under 12 months of age. METHODS: A retrospective review was performed
      in 14 infants under 12 months of age and 63 cases from 13 to 24 months of age
      with bilateral profound sensorineural hearing loss, who underwent unilateral
      cochlear implantation surgery. The operative parameters, including operation
      duration, amount of intraoperative bleeding, length of hospital stay, surgical
      complications and auditory outcomes, including warble tone average aided in free
      field, category of auditory performance (CAP), language behavior development
      quotient, babbling onset or spurt were recorded. RESULTS: There was no
      significant difference between infants younger than 12 months and older in
      operation duration, amount of intraoperative bleeding, except for the length of
      hospital stay. Otherwise, less complication occurred in younger group (7.1% and
      11.1%, respectively, chi(2) = 0.19, P > 0.05). The surgical highlights and
      experience, strictly restricted operation duration, intimate cooperation among
      the treatment team members and reduction of intraoperative bleeding are key
      points to ensure safety and success of the operation. The warble tone average
      aided in free field and language behavior developmental quotient of younger
      infants were both improved during follow-up and showed no significant difference
      compared with older group (t = 4.6 and 3.8, P > 0.05). 80% of infants who
      finished 24 months follow-up had a CAP score of 6 or 7. The babbling onset in
      younger group occurred at (14.1 +/- 0.9) months of life, which was better than
      that in older group [(22.6 +/- 3.0) months of life]. CONCLUSIONS: It is feasible
      to put cochlear implantation in infants under 12 months of age. And the earlier
      cochlear implantation could shorten auditory deprivation for children with
      bilateral congenital profound sensorineural hearing loss. Considering the high
      requirement of surgical highlights and experience, the suggest was that only
      experienced otologists challenge this domain cautiously.

PMID- 21176571
TI  - [Preliminary clinical research of cochlear implantation in elderly and pre
      elderly patients with profound hearing loss].
AB  - OBJECTIVE: To explore the safety and efficacy of cochlear implantation among
      elderly patients with severe to profound hearing loss. METHODS: Eight pre-elderly
      and elderly patients with an medium age of 58 years who suffered from bilateral
      severe to profound sensorineural hearing loss received cochlear implantation
      between November 2008 and November 2009. The patients' tolerance to implant
      surgery and the occurrence of complications were observed. Three months after
      switch-on, aided threshold and speech performance were measured. RESULTS: The
      surgery was uneventful in all cases with normal intraoperative neural response
      telemetry elicited. Three months after switch-on, average aided threshold across
      speech frequencies was 35 - 50 dB HL measured in sound field with warble tone.
      The results of speech audiometry showed large variation between individuals. Some
      patients achieved good performance in monosyllable recognition test, disyllables
      threshold test and sentences recognition test under both bubble noise and quiet
      conditions. CONCLUSIONS: Pre-elderly and elderly patients can endure a state of
      general anesthesia for cochlear surgery without complications. Cochlear implant
      can provide reconstruction of speech recognition capabilities for elderly
      patients suffering from severe to profound hearing loss. Cochlear implantation
      can improve the quality of life of elderly patients with hearing loss.

PMID- 21176572
TI  - [Analysis of reliability and validity of the Chinese version of Nijmegen Cochlear
      Implant Questionnaire].
AB  - OBJECTIVE: To investigate the reliability and validity of the Chinese version of
      Nijmegen Cochlear Implant Questionnaire (NCIQ). METHODS: There were six
      subdomains: basic sound perception, advanced sound perception, speech production,
      self-esteem, activities and social Interactions. The cross-cultural adaptation
      measures were used to translate the NCIQ into its Chinese version. Ninety-four
      cochlear implant users no younger than 18 years old were included. Test-retest
      analysis was administered randomly to 30 users without significant changes in
      health and social status during a two weeks' interval between test and retest.
      RESULTS: (1) Reliability: test-retest reliability of the NCIQ was proved to be
      satisfactory. All domains had coefficients that exceeded 0.70 (P < 0.01). Except
      for the subdomain, speech production, whose Cronbach's alpha score was 0.560,
      other Cronbach's alpha scores were greater than 0.700. (2) VALIDITY: The
      correlation coefficients between overall NCIQ scores and the six subdomains were
      0.620 - 0.810 (P < 0.01). There were weak or no correlations among the six
      subdomains. The evaluation of content validity by expert review showed the
      questionnaire had good content validity. NCIQ total scores in postlingually
      deafened users were significantly higher than those in prelingually deafened
      users (Z = 4.350, P = 0.000). This was also true for scores of the following
      subdomains:advanced sound perception (Z = 4.774, P = 0.000), speech production (Z
      = 4.416, P = 0.000), self-esteem (Z = 3.718, P = 0.000), activities (Z = 3.228, P
      = 0.001) and social interactions (Z = 3.001, P = 0.003). There was no significant
      difference between scores obtained from the two groups in the subdomain of basic
      sound perception (Z = 1.943, P = 0.052). CONCLUSIONS: The Chinese version of the
      NCIQ meets many psychometric criteria of a robust instrument. It possesses
      appropriate validity and good reliability, and can be used to measure the outcome
      of cochlear implant adults in China.

PMID- 21176573
TI  - [Effect of REZ-I cochlear implantation on residual hearing in adult patients].
AB  - OBJECTIVE: To evaluate the effect of cochlear implantation with REZ-I straight
      electrodes on residual hearing of postlingually deafened adults, and to explore
      the audiologically safety and injury characteristics of cochlear implantation.
      METHODS: Sixteen unilateral REZ-I (22 channels) cochlear implantation recipients
      from September 2009 to December 2009 were picked out. Their pre-and post
      implantation audiometry data including pure-tone audiometry (PTA), auditory
      steady-state responses (ASSR), auditory brainstem responses (ABR) and distortion
      product otoacoustic emissions (DPOAE) were retrospectively analyzed, in order to
      compare the change between pre- and post-implantation residual hearing. RESULTS:
      Among the 12 recipients who had some measurable residual hearing before
      implantation, 5 (41.6%) patients had conserved some measurable hearing but the
      other 7 (58.4%) recipients had lost all measurable hearing after implantation on
      the implanted side. The implanted ears had an average PTA threshold drop of 9.5
      dB HL and a statistically significant difference between pre- and post
      implantation (P < 0.05) PTA thresholds in the frequencies of 250 Hz, 500 Hz, 1000
      Hz, 2000 Hz and 4000 Hz. Compared to non-implanted ears, the drop in 500 Hz and
      1kHz had a statistically significant difference between pre- and post
      implantation PTA thresholds (P < 0.05). The ASSR residual hearing threshold
      elevation were statistically significant (P < 0.05) between pre- and post
      implantation ASSR at 250 Hz and 500 Hz on the implanted side, while the The ASSR
      residual hearing threshold elevation were statistically significant (P < 0.05) at
      500 Hz when compared to non-implanted side. The difference of residual hearing
      between pre- and post-implantation was not statistically significant for both
      DPOAE and ABR. CONCLUSION: There will be a certain degree of damage to residual
      hearing of the implanted side following REZ-I cochlear implantation.

PMID- 21176575
TI  - [Diagnosis and treatment of congenital fourth branchial anomaly].
AB  - OBJECTIVE: To discuss the anatomic features, clinical presentations, diagnosis,
      differentiations and treatments of congenital fourth branchial anomaly(CFBA).
      METHODS: The clinical data of 8 patients with CFBA were retrospectively analyzed.
      RESULTS: Of the 8 patients aging from 27 to 300 months (median age: 114 months),
      4 male and 4 female; 3 untreated previously and 5 recurrent. All lesions,
      including 1 cyst, 3 sinus (with internal opening) and 4 fistula, located in the
      left necks. Three patients presented acute suppurative thyroiditis, 4 deep neck
      abscesses, and 1 neck lump. Preoperative examinations included barium
      esophagogram, direct laryngoscopy, ultrasonography, CT, MRI, and so on. The
      principles of managements were adequate drainage, infection control during acute
      period and radical surgery during quiescent period. Classic surgical approach
      consisted of complete excision of branchial lesions, dissection of recurrent
      laryngeal nerve and partial thyroidectomy. Selective neck dissection was applied
      in recurrent cases to extirpate branchial lesions, scarrings and inflammatory
      granuloma. Postoperatively, 1 case was with local incision infection which healed
      by wound care; 1 case was with temporary vocal cord paralysis which completely
      recovered 1 month after operation. No recurrence was found in all of 8 cases with
      follow-up of 13 to 42 months (median: 21 months). CONCLUSIONS: CFBA relates
      closely anatomically with recurrent laryngeal nerve and thyroid grand. The barium
      esophagogram and direct laryngoscopy are the most useful diagnostic tools. CT and
      MRI are all beneficial to the diagnosis of CFBA. The treatment key to CFBA is the
      complete excision of lesion during a quiescent period after inflammatory control,
      together with the dissection of recurrent laryngeal nerve, partial thyroidectomy
      and partial resection of lamina of thyroid cartilage (if necessary), which all
      can decrease the risk of complications and recurrence. For recurrent cases,
      selective neck dissection is a safe and effective surgical procedure.

PMID- 21176574
TI  - [Study on hemorrhage following coblation assisted uvulopalatopharyngoplasty].
AB  - OBJECTIVE: To compare the postoperative hemorrhage between standard
      uvulopalatopharyngoplasty (UPPP) and coblation assisted UPPP, and to evaluate the
      related risk factors and preventive measures. METHODS: Five hundreds and ninety
      seven patients with obstructive sleep apnea hypopnea syndrome (OSAHS) underwent
      UPPP and coblation assisted UPPP between January 1, 1999, and September 30, 2009
      were reviewed retrospectively. Two hundred and sixty three patients with
      coblation assisted UPPP and 334 patients with standard UPPP were treated
      respectively. Single factor statistic analysis, multiple factors Logistic regress
      statistic analysis and Wilcoxon test method for related risk factors were
      applied. RESULTS: A total of 42 patients (7.0%) experienced postoperative
      bleeding. Among them, 24 patients with coblation assisted UPPP (9.1%) and 18
      patients with UPPP (5.4%) had postoperative hemorrhage. Significant difference
      was not found in the degree of hemorrhage (z = 0.784, P > 0.05), hemorrhage
      site(chi(2) = 1.387, P > 0.05) and postoperative hemorrhage rates (chi(2) = 3.14,
      P > 0.05) between the two surgical techniques. Significant difference was found
      in the interval of hemorrhage after surgery between the two surgical techniques
      (chi(2) = 9.25, P < 0.01). History of hypertension, smoking, hepatic dysfunction
      was found to be correlated with the postoperative hemorrhage (Odd-ratio were
      respectively 7.326, 3.674, 2.707). CONCLUSION: Coblation technique did not
      significantly increase UPPP postoperative hemorrhage.

PMID- 21176576
TI  - [Helicobacter pylori infection: a potential pathogenic factor for laryngeal
      squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the difference in Helicobacter pylori (Hp) infection
      rate between the patients with laryngeal squamous cell carcinoma and the patients
      with benign laryngeal lesions and to explore the role of Hp infection in the
      pathogenesis of laryngeal squamous carcinoma. METHODS: Nested polymerase chain
      reaction (nPCR) and Hp culture were used to identify the Hp in laryngeal mucosa
      in 30 patients with laryngeal carcinoma and 15 patients with benign laryngeal
      lesions including polyps of vocal cords or epiglottic cysts. RESULTS: nPCR showed
      that Hp-positive rate (73.3%) of patients with laryngeal carcinoma was
      significantly higher than that (20.0%) of control patients with benign laryngeal
      lesions (chi(2) = 11.520, P = 0.010). Regarding the 22 positive neoplastic cases
      that have 44 tissues, out of the 22 tumor tissues, 10 were positive with Hp
      (45.4%), and among 22 tissues beside the tumor, 19 were positive (86.4%). This
      event also indicated a statistical significance (chi(2) = 4.697, P = 0.030). Hp
      culture showed that Hp was negative in all specimens. CONCLUSIONS: Hp exist in
      the laryngeal mucosa, but with the higher rate of Hp infection in the patients
      with laryngeal squamous cell carcinoma than that in the patients with benign
      laryngeal lesions, which suggests Hp may be one of pathogenic factors of
      laryngeal squamous cell carcinoma.

PMID- 21176577
TI  - [Endoscopic endonasal anatomy of pterygopalatine fossa and infratemporal fossa:
      comparison of endoscopic and radiological landmarks].
AB  - OBJECTIVE: To investigate the feasibility and reliability of the measurement of
      critical anatomic landmarks of endoscopic endonasal anatomy of pterygopalatine
      fossa and infratemporal fossa using multislice spiral computed tomography (MSCT),
      and to illustrate the spatial relationship of the surgical landmarks in
      pterygopalatine fossa and infratemporal fossa through an endoscopic endonasal
      view and radiological images. METHODS: Included in this study were eleven fixed
      cadaver heads (22 pterygopalatine fossa and infratemporal fossa), which were
      prepared from MSCT scans for establishing a spatial coordinates system to
      calculate the radiological anatomic data and attaining 3D reconstruction image,
      and also were anatomically dissected to get anatomic data. The anatomic data in
      two groups were compared, the endoscopic and radiological images of the same
      regions acquired during the endoscopic endonasal approaches observed. RESULTS:
      The distance (x(-) +/- s) from nasal columella to sphenopalatine foramen,
      pterygoid canal, foramen rotundum, foramen ovale, foramen spinosum, carotid
      canal, foramen lacerum in radiological group were: (68.83 +/- 3.00), (72.49 +/-
      2.88), (75.26 +/- 3.14), (88.55 +/- 5.00), (95.19 +/- 4.31), (106.76 +/- 3.77),
      (88.16 +/- 2.87) mm and in anatomic group were: (68.90 +/- 3.04), (72.73 +/-
      3.08), (75.44 +/- 3.07), (89.75 +/- 4.13), (96.22 +/- 3.37), (106.68 +/- 3.75),
      (88.47 +/- 2.64) mm. There was no statistical difference between two groups (t
      value were -0.856, -1.134, -0.920, -1.923, -1.903, 2.820 and 1.209, respectively,
      all P > 0.05). Sphenopalatine foramen, pterygoid canal, foramen rotundum, foramen
      ovale, foramen spinosum, foramen lacerum, carotid canal were the corresponding
      anatomic structures in endoscope and radiology, which provided the surgeons with
      anatomic landmarks to identify the spatial relationship of the surgical
      structures in pterygopalatine fossa and infratemporal fossa. CONCLUSIONS: MSCT
      measurements of anatomic landmarks are feasible and reliable, can be used in
      clinical individualized surgery. The corresponding anatomic structures of
      endoscopic and radiological landmarks provide useful reference to surgeons when
      operating in these areas through an endoscopic endonasal approach.

PMID- 21176578
TI  - [Experimental study of cervical lymph node in thyroid by using radioactive nano
      tracer].
AB  - OBJECTIVE: Using radioactive nano tracer with different sizes (average diameter
      were 50, 80 and 100 nm) and dosages (0.01 and 0.02 ml) in the thyroids of
      rabbits, to study the drainage of thyroid to cervical lymph nodes (LNs) in
      rabbits and to provide experimental evidence for the choice of ideal sizes and
      dosages of radioactive Nano tracer for the sentinel lymph node biopsy (SLNB) in
      thyroid cancer patients. METHODS: Thirty adult rabbits were randomly divided into
      six groups (50 nm - 0.01 ml, 50 nm - 0.02 ml, 80 nm - 0.01 ml, 80 nm - 0.02 ml,
      100 nm - 0.01 ml, 100 nm - 0.02 ml of (99m)Tc-Sb(2)S(3)) with five rabbits in
      each group. A total of 60 sides of thyroids were included. The mean number of LNs
      with radioactivity, the initial, the strangest and the lasting time of
      radioactivity in LNs in each group were measured. RESULTS: One to three LNs were
      identified in one side neck of rabbits, totally 86 LNs. Most of LNs with
      radioactivity existed in level VI, counting for 75.6% (65/86). (99m)Tc-Sb(2)S(3)
      with 50 nm particles was significantly better than that with 80 nm or 100 nm
      particles with regarding the initial and the strangest radioactive time of
      (99m)Tc-Sb(2)S(3) in LNs (P < 0.05). There were no significant difference in the
      mean number of LNs with radioactivity, the initial, the strangest and the lasting
      time of radioactivity between the dosages of 0.01 ml and 0.02 ml of (99m)Tc
      Sb(2)S(3) with same size of particles (P > 0.05). CONCLUSION: (99m)Tc-Sb(2)S(3)
      with 50 nm particles, in the dosage of 0.01 ml or 0.02 ml, could be good choice
      for SLNB of thyroid cancer.

PMID- 21176579
TI  - [Nimesulide induced apoptosis and inhibited metastasis of hypopharyngeal
      carcinoma cells].
AB  - OBJECTIVE: To investigate the effects of Nimesulide, a selective Cox-2 inhibitor,
      on the apoptosis, invasion and migration of hypopharyngeal carcinoma cell line
      (FaDu). METHODS: Viabilities of FaDu cells treated with various concentrations of
      Nimesulide were detected by MTT assay. Morphological changes were observed by
      acridine orange cytochemistry staining. Apoptosis was examined by flow cytometry.
      The ability of invasion and migration of cells was detected by Transwell
      chambers. The mRNA and protein expressions of Cox-2, MMP-9 and caspase-3 in
      response to Nimesulide were examined by RT-PCR and Western blot, respectively.
      RESULTS: MTT assay showed that the cell surviving rates significantly decreased
      in time- and concentration-dependent manners (P < 0.05). The typical
      morphological changes of apoptotic cells were observed. Percent of apoptosis
      after 6 h Nimesulide treatment was (32.4 +/- 6.1)%. The metastatic cells were
      decreased by Nimesulide to about 20%. Nimesulide decreased the expressions of Cox
      2 and MMP-9, whereas increased expression the of Caspase-3. CONCLUSION:
      Nimesulide could induce the apoptosis and inhibit metastasis of FaDu cells.

PMID- 21176580
TI  - [Type of adenoidal hypertrophy by nasal endoscopic and clinical significance].

PMID- 21176581
TI  - [Small incision of endoscopic thyroidectomy experience in 292 cases].

PMID- 21176582
TI  - [Fiberoptic bronchoscope guided intubation low-pressure cuff on tracheal
      intubation expansion for prevention traumatic stenosis].

PMID- 21176583
TI  - [Clinical analysis of 11 cases of Mikulicz disease in the salivary glands].

PMID- 21176584
TI  - [Metastasis of renal cell carcinoma to the thyroid gland: one case study].

PMID- 21176585
TI  - [Low-grade myofibroblastic sarcoma of the larynx: a case report].

PMID- 21176586
TI  - [Summary of 2010 national expert forum on artificial hearing].

PMID- 21176587
TI  - [Progress in Cetuximab treatment of squamous cell carcinoma of the head and
      neck].

PMID- 21176588
TI  - [Implantable artificial hearing equipment].

PMID- 21176589
TI  - [My viewpoint on cleft lip and palate treatment].

PMID- 21176590
TI  - [Classification and surgical treatment of the deviated nose with unilateral cleft
      lip].
AB  - OBJECTIVE: To present a classification of the deviated nose with unilateral cleft
      lip and the associated surgical correction. METHODS: A total of 176 cases of
      nasal deformities with unilateral cleft lip treated in Department of Oral and
      Maxillofacial Surgery, Ninth People's Hospital, College of Stomatology, Shanghai
      Jiao Tong University School of Medicine & Shanghai Research Institute of
      Stomatology & Shanghai Key Laboratory of Stomatology from 2007 to 2009 were
      analyzed. Depending on the relationship between the external pyramid and the
      facial midline, the nasal deviations with cleft lip were classified into 3 types:
      I, deviated bony pyramid, II, deviated cartilaginous pyramid; III, deviated
      lobular. The surgical treatment included surgical correction of deviated bony
      pyramid, deviated cartilaginous pyramid, deviated lobular and deviated septa.
      RESULTS: Among the 176 patients, there were 97 males and 79 females, aging from
      16 to 42 years with a mean of 20. There were 93 patients without deviated and 83
      patients with deviated. Among the 83 deviated patients, deviated bony pyramid was
      found in 8 (10%), deviated cartilaginous pyramid in 29 (35%), deviated lobular in
      46 (55%). Most patients who underwent surgical correction were satisfied.
      CONCLUSIONS: There were nearly half of the unilateral cleft lip nasal deformity
      presenting with deviated noses. There was least deviated bony pyramid and most
      deviated lobular in the unilateral cleft lip deviated nose. The proposed
      classification for the deviated nose with unilateral cleft lip could serve as a
      practical guide for surgical planning.

PMID- 21176591
TI  - [Relationship between the oral language development and restoration of
      velopharyngeal closure function in Chinese toddlers with repaired cleft palate].
AB  - OBJECTIVE: To evaluate how the oral language development enhances articulators to
      function well in cleft palate movement and velopharyngeal closure in the young
      Chinese children with repaired cleft palate. METHODS: The recordings of 78 cases
      of Chinese toddlers with repaired cleft palate were reviewed. This group of
      children aged from 27 months to 33 months (average: 30 months). Transcription
      using Pinyin system was made. Mean utterance count (MUC) and mean special
      consonant correct count (MSCC) were calculated. Correlation between MUC and MSCC
      was statistically analyzed. RESULTS: The correlation coefficient of MUC and MSCC
      is 0.360 (P < 0.01). CONCLUSIONS: There is positive correlation between the oral
      language development and restoration of velopharyngeal closure function. Children
      with repaired cleft palate should be encouraged to start oral language as early
      as possible and as much as possible in order to get the restoration of
      velopharyngeal closure function.

PMID- 21176592
TI  - [Magnetic resonance imaging of the levator veli palatini of the cleft palate
      patients after operation].
AB  - OBJECTIVE: To observe the mobility of levator veli palatini muscle during speech
      in patients with repaired cleft palate and cleft lip. METHODS: MRI of the levator
      veli palatini muscle was taken during speech and breathing in three groups of
      patients: control group (cleft lip only, 8 cases), velopharyngeal incompetence
      (VPI) group (7 cases), velopharyngeal competence (VPC) group (10 cases). The
      length and the angle of the levator veli palatini muscle were compared. RESULTS:
      The changes of the length and the angle during speech were not significantly
      different among the three groups (P > 0.05). The ratio of length changes when
      speaking "a", "i", and "m" are (13.5 +/- 11.7)%, (11.1 +/- 10.8)%, (8.2 +/-
      14.3)%. Mean angle of pronouncing "a", "i", and "m" are [(43.18 +/- 4.984)
      degrees , (43.08 +/- 4.879) degrees , (39.48 +/- 5.046) degrees ]. The levator
      veli palatini muscle contracted progressively form "m", "i", to "a". CONCLUSIONS:
      The mobility of the levator veli palatini muscle in patients with repaired cleft
      palate and cleft lip only is basically the same.

PMID- 21176593
TI  - [Division of flap in cleft palate patients after posterior pharyngeal flap
      surgery].
AB  - OBJECTIVE: To investigate the reasons of flap division in patients with posterior
      pharyngeal flap and the outcome of the flap division for treating secondary
      velopharyngeal insufficiency (VPI) and obstructive sleep apnea-hypopnea syndrome
      (OSAHS). METHODS: Twenty patients who underwent flap division after posterior
      pharyngeal flap surgery were included in this study, including 11 incomplete
      cleft palate and 9 complete cleft palate). Nasal endoscopy and lateral
      cephalometric radiographs were performed for all the patients preoperatively.
      Speech recordings were made pre- and post-operatively. The respiratory status of
      patients who had OSAHS manifestations was monitored by polysomnography. Simple
      division of the flap was carried out in 14 cases, and additional pharyngoplasty
      combined the division of posterior pharyngeal flap was performed in six cases.
      RESULTS: The speech did not show significant improvement in 14 cases after
      posterior pharyngeal flap surgery but improved after flap division. Three cases
      got speech improvement, but developed the respiratory obstruction causing sleep
      apnea. After the division of flap, the respiratory status got improved. Three
      cases required orthognathic surgery under general anesthesia, which demanded the
      division of flap simultaneously. The speech did not change after the division.
      CONCLUSIONS: If OSAHS occurred or VPI remained after posterior pharyngeal flap
      surgery, the division of the flap or additional pharyngoplasty should be
      performed. It is suggested that the operation of the flap division be done six
      months after posterior pharyngeal flap surgery.

PMID- 21176594
TI  - [The correlation analysis between environmental factors, bone morphogenetic
      protein-4 and transforming growth factor beta-3 polymorphisms in nonsyndromic
      cleft lip with or without cleft palate].
AB  - OBJECTIVE: To investigate the effects of interactions among environmental
      factors, bone morphogenetic protein-4 (BMP4) and transforming growth factor beta
      3 (TGF-beta(3)) polymorphisms on nonsyndromic cleft lip and cleft palate (NSCLP).
      METHODS: The data of environmental exposures were collected with questionnaires.
      Genotypes were determined with techniques of polymerase chain reaction
      restriction fragment length polymorphism. Interactions between genes,
      environmental factors and NSCLP were analyzed using multifactor dimensionality
      reduction (MDR) method. The interactions were validated by logistic regression
      analysis. RESULTS: There was no correlation between three single nucleotide
      polymorphism (SNP) associated with NSCLP. The developmental accident of NSCLP had
      higher risk in the interaction between BMP4 T538C, maternal passive smoking and
      infection in first trimester pregnancy, as well as in the interaction of six
      factors between TGF-beta(3) G15572-, maternal passive smoking, infections,
      multivitamin supplement in the first trimester pregnancy, paternal smoking and
      high risk drinking before realizing pregnancy than in other interactions of
      environmental factors. The results could be validated by logistic regression
      analysis. CONCLUSIONS: The NSCLP is induced by the interactions between genes and
      environmental risk factors.

PMID- 21176595
TI  - [Correction of maxillary hypoplasia secondary to cleft lip and palate: report of
      two cases].

PMID- 21176597
TI  - [Assessment and treatment of articulation disorders in postoperation of patients
      with or without cleft palate].

PMID- 21176596
TI  - [The study of genetic and physical characteristics for predicting the risk for
      development of cleft lip with or without cleft].

PMID- 21176598
TI  - [Relationship between transforming growth factor beta-1 gene-509C/T polymorphism
      and severe chronic periodontitis].
AB  - OBJECTIVE: To investigate the relationship between transforming growth factor
      beta-1 (TGF-beta(1)) gene-509C/T polymorphism and severe chronic periodontitis in
      Chinese Hans population. METHODS: TGF-beta(1)-509C/T genotype polymorphism was
      analyzed in 102 patients with severe chronic periodontitis (periodontitis group)
      and 102 healthy controls (control group) by polymerase chain reaction restriction
      fragment length polymorphism (PCR-RFLP) method. RESULTS: The distributions of TGF
      beta(1)-509C/T genotype and allele were significantly different between severe
      chronic periodontitis group and control group (P < 0.05). TGF-beta(1)-509CC, CT
      and TT genotype frequency were 44.1% (45/102), 47.1% (48/102), 8.8% (9/102) in
      periodontitis group and 29.4% (30/102), 51.0% (52/102), 19.6% (20/102) in control
      group, respectively. The relative risk analysis found that C allele carriers had
      higher risk of suffering from severe chronic periodontitis compared with T allele
      carriers (OR = 1.718, 95%CI: 1.148-2.569). CONCLUSIONS: TGF-beta(1)-509C/T
      polymorphism is associated with severe chronic periodontitis in Chinese Hans
      population, and C allele may be an important genetic susceptibility gene for
      severe chronic periodontitis.

PMID- 21176599
TI  - [Analysis of outer membrane proteins in various strains of Porphyromonas
      gingivalis by surface enhanced laser desorption/ionization time-of-flight mass
      spectrometry].
AB  - OBJECTIVE: To analyze the common outer membrane proteins (OMP) from Porphyromonas
      gingivalis (Pg) by surface enhanced laser desorption/ionization time-of-flight
      mass spectrometry (SELDI-TOF-MS) and to provide antigens for the subsequent
      experiments in screening vaccine for periodontitis therapy. METHODS: Four strains
      of Pg were cultured under anaerobic conditions. The common OMP was extracted
      through ultracentrifugation and SELDI-TOF-MS was employed to detect the
      expressions of proteomes by chip H(50). The data was analyzed by Biomarker
      Wizard. RESULTS: Four kinds of strains of OMP fingerprint spectrum were obtained.
      Seventy-one proteins of PgATCC33277, 74 proteins of PgW83, 76 proteins of PgW301
      and 72 proteins of Pg381 were captured by chip H(50). Thirteen common proteins
      were identified according to fingerprint spectrum. There was only 1 of the 13
      common proteins identified in NCBI protein bank. CONCLUSIONS: SELDI-TOF-MS has
      good reproducibility and high sensibility and can be used to identify the common
      OMP of Pg. The 13 proteins have a potential value in the screening vaccine
      candidate antigen sites for periodontitis.

PMID- 21176600
TI  - [Effects of sodium butyrate on proliferation of human oral squamous carcinoma
      cell line and expression of p27Kip1].
AB  - OBJECTIVE: To investigate the effect of sodium butyrate (NaB) on inhibition of
      human oral squamous carcinoma cell line. METHODS: Human oral squamous carcinoma
      cell line Tca8113 was treated with different concentration of NaB. Light
      microscope was used to observe the morphological changes of the carcinoma cells.
      The cell cycle was analyzed by flow cytometry. Expression of p27(Kip1) was
      determined with immunocytochemical assay. RESULTS: NaB significantly inhibited
      the proliferation of Tca8113 in a time- and dose-dependent manner. Tca8113 cells
      treated with NaB was arrested in G(0)-G(1) phase. The fraction of cells in G(0)
      G(1) were (63.2 +/- 2.4)% and (77.2 +/- 3.8)% after treated with NaB at the
      concentration of 2 and 4 mmol/L alternatively, whereas (48.1 +/- 2.4)% in G(0)
      G(1) phase were observed in control group (P < 0.05). The expression of p27(Kip1)
      was markedly up-regulated after being treated with NaB. CONCLUSIONS: NaB
      treatment can inhibit the growth of oral squamous carcinoma cell line in vitro
      and induce cell cycle arrest, which might be associated with the increased
      expression of p27(Kip1) protein.

PMID- 21176601
TI  - [Expression of integrin-linked kinase in oral squamous cell cancinoma and its
      significance].
AB  - OBJECTIVE: To investigate the expression patterns of integrin-linked kinase (ILK)
      in oral squamous cell carcinoma (OSCC). METHODS: The expression of ILK in 170
      OSCC cases was examined by immunohistochemistry and periodic acid-schiff
      histochemistry. RESULTS: ILK immunoreactivity occurred in cancer cells and(or)
      stroma encircling the malignant tissue. Along with the deteriorated
      histopathologic grade of oral cancer, there was stepwise aberration exhibiting
      from ILK-negative, to ILK-positive in epithelia, to ILK-positive in both
      epithelia and stroma, and to ILK-positive in stroma. Through non-parameter test,
      in both lymphatic invasion [ILK-positive in stroma in well-differentiated,
      moderately-differentiated and poorly-differentiated is 2% (1/50), 18% (6/33) and
      64% (18/28), respectively] and non-lymphatic invasion group [ILK-positive in
      stroma in well-differentiated, moderately-differentiated and poorly
      differentiated is 16% (4/25), 9/18 and 10/16, respectively), the expression
      patterns of ILK exhibited significant correlations with histopathology (F =
      17.742, P < 0.001, F = 4.394, P = 0.017). ILK expression between lymphatic
      metastasis and non-lymphatic metastasis group was significantly different (chi(2)
      = 14.418, P = 0.002). CONCLUSIONS: ILK inclines to express in stroma during the
      OSCC progress.

PMID- 21176602
TI  - [Effects of estrogen on the expression of phosphofructokinase muscle-specific
      isoform in genioglossus of chronic intermittent hypoxia rats].
AB  - OBJECTIVE: To investigate the effects of estrogen on the expression of
      phosphofructokinase muscle-specific isoform (PFK-M) in genioglossus of chronic
      intermittent hypoxia (CIH) rats. METHODS: Fifty male SD rats were randomly
      divided into five groups: the normal control group (NC), the chronic intermittent
      hypoxia group (CIH), and three doses of estrogen plus hypoxia groups (LE, ME,
      HE). Rats in the latter four groups were used to build CIH models (8 h/d, 5
      weeks). In the mean time, rats in the latter three groups were injected with
      three dose levels of estrogen (0.1, 0.2, 0.3 mg/kg), and rats in NC and CIH
      groups were injected with sterile olive oil as control. At the end of the
      treatment, the genioglossus was isolated and quickly removed. The mRNA levels of
      PFK-M were determined by real-time RT-PCR and the protein content of PFK-M was
      detected by Western blotting analysis. RESULTS: PFK-M mRNA and protein in CIH
      group (2.144 +/- 0.260, 0.875 +/- 0.025) were both higher than those (1.000 +/-
      0.259, 0.413 +/- 0.013) in NC group (P < 0.05). The expression of PFK-M mRNA in
      LE, ME and HE groups were 1.424 +/- 0.193, 1.395 +/- 0.251 and 1.310 +/- 0.094,
      respectively. The expression of protein in LE, ME and HE groups were 0.638 +/-
      0.015, 0.576 +/- 0.017 and 0.505 +/- 0.021, respectively. Compared with CIH
      group, the expression of PFK-M mRNA and protein in LE, ME and HE groups were all
      inhibited significantly (P < 0.05). Among the three treatment groups, decreased
      protein content of PFK-M was observed only in HE group when compared with LE
      group (P < 0.05), but no significant difference was detected in the expression of
      PFK-M mRNA. CONCLUSIONS: CIH exposure could increase the expression of PFK-M mRNA
      and protein in rat genioglossus, while estrogen administration could dose
      dependently inhibit the overexpression.

PMID- 21176603
TI  - [A computer aided design approach of all-ceramics abutment for maxilla central
      incisor].
AB  - OBJECTIVE: To establish the computer aided design (CAD) software platform of
      individualized abutment for the maxilla central incisor. METHODS: Three
      dimentional data of the incisor was collected by scanning and geometric
      transformation. Data mainly included the occlusal part of the healing abutment,
      the location carinae of the bedpiece, the occlusal 1/3 part of the artificial
      gingiva's inner surface, and so on. The all-ceramic crown designed in advanced
      was "virtual cutback" to get the original data of the abutment's supragingival
      part. The abutment's in-gum part was designed to simulate the individual natural
      tooth root. The functions such as "data offset", "bi-rail sweep surface" and
      "loft surface" were used in the process of CAD. RESULTS: The CAD route of the
      individualized all-ceramic abutment was set up. The functions and application
      methods were decided and the complete CAD process was realized. CONCLUSIONS: The
      software platform was basically set up according to the requests of the dental
      clinic.

PMID- 21176605
TI  - [To expand the grand prospect of Chinese Journal of Ophthalmology following the
      fine tradition].
AB  - When we celebrate the diamond jubilee of Chinese Journal of Ophthalmology (CJO),
      we also reviewed its past and prospected its future. Under the effort by the
      editorial members and the great majority of ophthalmologists for sixty years, CJO
      has become the most authoritative and academic journal in ophthalmology in China,
      and has formed the fine tradition of "to respect the profession, to believe the
      truth and to advance bravely". At present, CJO has a basis to further become the
      most authoritative academic journal in ophthalmology not only in the domestic but
      also in the world. For realizing the grand prospect, we should do more arduous
      effort for facing the all kind of the challenges in our ways forward; we should
      let the editorial committee to play the full role in our work; we should continue
      to raise the professional level of all editorial personnel; we should make great
      efforts to find and edit more and more articles with the high quality; we should
      observe the morals and ethics for editorial personnel; we should hear and accept
      the opinions, suggestions and criticisms; we should strength the international
      cooperation and communication.

PMID- 21176604
TI  - [Measurement of tactile threshold of natural teeth and its clinical
      significance].
AB  - OBJECTIVE: To measure passive tactile threshold of natural teeth in six
      orthogonal orientations, to analyze impact factors, and to guide the occlusal
      adjustment in a personalized manner. METHODS: The passive tactile thresholds of
      218 natural teeth from 20 healthy subjects were measured in six orthogonal
      orientations using a digital test system for tactile function of teeth. The
      subjects were composed of 10 males and 10 females, with a mean age of 25 years.
      The natural teeth were tested from central incisors to first molars in maxilla
      and mandible. The passive tactile thresholds of teeth were measured respectively
      in the four horizontal orientations of labial (buccal), lingual, mesial and
      distal, and the two axial orientations of apical and coronal. The multilevel
      modeling (MLM) was used to analyze impact factors. RESULTS: The passive tactile
      thresholds of anterior teeth, premolars and molars were 16 (18), 38(57) and 105
      (115) mN respectively. The difference between subjects was of statistical
      significance (P < 0.05). The three factors of tooth, gender and orthogonal
      orientation were disclosed to influence the passive tactile threshold of natural
      teeth (P < 0.01). The influence level of the factors was tooth > gender >
      orthogonal orientation. CONCLUSIONS: A force level of 10 mN could be detected by
      natural teeth. There was statistical difference in the passive tactile threshold
      between subjects. The passive tactile threshold was affected with tooth, gender
      and orthogonal orientation.

PMID- 21176606
TI  - [Sailing kilometers for success means a heavy responsibility to bear and a long
      way to go].
AB  - Reviewing the 60-year history of Chinese Journal of Ophthalmology, we realise
      that it is now a tough period for journals and find the proper measure to deal
      with it. With the periodical achievements acknowledged, we focus more on the
      historical mission and responsibility of the future development as the publishers
      of Chinese Journal of Ophthalmology.

PMID- 21176607
TI  - [Advances in basic and clinical corneal research].
AB  - It is well known that corneal epithelial stem cells reside in the limbal basal
      layer. Recently, it has been found that oligopotent stem cells, located in the
      basal layer of corneal epithelium, can repair epithelial cell damage. Although
      corneal endothelial cells usually could not regenerate in vivo, stem cells have
      been detected in the endothelial cell layer and can convert into endothelial
      cells under certain circumstances. Stem cells are also present in corneal stroma.
      The heterogeneous stromal cells manifest features of neural crest progenitor
      cells in some situations, which make latent herpes simplex virus-1 infection
      possible. Moreover, the finding that the hyphal growth of different fungal
      pathogens shows different patterns in the cornea. This finding significantly
      promotes the surgical treatment of fungal keratitis. The major risk factor of
      acanthamoeba keratitis in China is trauma caused by plants or soil, which is
      different from developed countries, in which the major risk factor is contact
      lens wear. This finding provides important new information for clinical diagnosis
      of this disorder. Advances in basic and clinical corneal research in the last
      five years are reviewed in this article.

PMID- 21176608
TI  - [Advances and prospects in studies of cataract in the past five years in China].
AB  - In the past five years, the cataract surgery rate increased in China. Cataract
      researches has made significant achievements and has gradually geared
      international standard. Along with the trend of increasing visual quality
      requirement to a higher level, studies of cataract face new opportunities and
      challenges. This article reviews the progress and problems of cataract studies in
      the past five years in China in order to make further development in this field.

PMID- 21176609
TI  - [New progresses of glaucoma research in China and abroad].
AB  - Great progresses have recently been made in glaucoma fields, including basic
      research and clinical management. This review covers major areas in the study of
      glaucoma, including epidemiology, pathogenesis, integrated imaging technology,
      medicine, laser and surgical therapy of glaucoma, as well as the new trends of
      development. This paper provides the future direction in the research of
      glaucoma.

PMID- 21176610
TI  - [Up-to-date development of diagnosis and treatment technology of ocular fundus
      diseases in the past 5 years in China].
AB  - In the past 5 years, the diagnosis and management of ocular fundus diseases in
      China has been improved remarkably. Up-to-date international concepts of
      diagnosis and management, methods, and equipment have been introduced into China,
      which have promoted the therapeutic technology of ocular fundus diseases. In the
      field of diagnosis, the application of frequency-domain optical coherence
      tomography and fundus autofluorescence detection technology not only provided
      more detailed image information for clinical diagnosis, but also helped clinical
      ophthalmologists to understand the features and pathogenesis of ocular fundus
      diseases comprehensively, leading the doctors into a new era of examination of
      ocular fundus diseases. In the field of treatment, Chinese researchers actively
      performed innovative clinical studies, such as organizing domestic multi-center
      studies of various therapies of macular hole retinal detachment, developing full
      length humanized antibody fusion protein KH902 with intellectual property rights,
      using implants of autologous retinal pigment epithelium patch with Bruch membrane
      to treat age-related macular degeneration, using photodynamic therapy to treat
      central serous chorioretinopathy, 20 gauge small incision vitrectomy and surgical
      therapy of central retinal artery occlusion, etc. Moreover, certain amounts of
      high quality clinical papers have been published in SCI journals, which showed
      that clinical research of ocular fundus diseases in China has entered the field
      of international ophthalmology and has geared to international standards.

PMID- 21176611
TI  - [Progress in research of pediatric ophthalmology and strabismus in China in past
      5 years].
AB  - In the past 5 years of the new century, with the development of national power
      and the accompanied increase of international academic communication, the
      researchers and clinical scientists of pediatric ophthalmology and strabismus in
      China actively participated in the international academic communication and
      competition and made great achievements. Many excellent works of clinical studies
      or basic researches in this field were recognized by the academic community of
      the world. Young ophthalmologists in pediatric ophthalmology and strabismus have
      been trained and well developed. The position of Chinese pediatric ophthalmology
      and strabismus in the global academic community has been moved up gradually.

PMID- 21176612
TI  - [Eye injuries in China: a five-year update].
AB  - Remarkable advance for the treatment of opening eye injuries have been achieved
      in the past 5 years. Very valuable results have been obtained from the database
      of cumulative studies on eye injuries managed with vitrectomy. Timing of
      vitrectomy for opening-injured eyes was a significant factor to influence their
      outcome. Estimation of a quarter of injured eyes with no light perception could
      gain anatomic recovery with various improvement of visual acuity. Previous
      conventional treatment pattern for opening anterior segment injury lacked proper
      debridement on inside of wound which resulted unfavorable outcome. Vitrectomy at
      early stage (1-3 weeks after initial repair of wound) in selected cases could be
      a recommended treatment to improve outcomes in opening anterior segment injury.

PMID- 21176613
TI  - [Five-year overview of progress of oculoplastic surgery studies in China].
AB  - Even though started behind others, we have made an unprecedented development in
      oculoplastic surgery by the efforts of all ophthalmologists in China. Basic
      research and clinical applications of biomaterials have promoted the development
      of oculoplastic surgery greatly. Tissue engineering techniques have been used to
      construct artificial bone for repairing orbital bone defect, this is at the
      cutting edge of tissue construction and repair of defects. Moreover, with the
      development of ophthalmology, maxillofacial surgery, microsurgery and with the
      application of endoscopic technique and computer analysis and design,
      oculoplastic surgery has improved significantly and has been utilized in a wide
      field as never before. We anticipate that oculoplastic surgery can be developed
      continuously in the next 5-10 years.

PMID- 21176614
TI  - [Five-year overview of progress of ophthalmic pathology studies in China].
AB  - To commemorate the 60th anniversary of Chinese Journal of Ophthalmology, here we
      briefly review the progress in the field of ophthalmic pathology. Recalling the
      development of ophthalmology in China, ophthalmic pathology has made numerous
      achievements and kept developing steadily. The field of ophthalmic pathology has
      been extended and remarkable scientific outcomes have been accomplished. This
      article concisely summarizes the development of ophthalmic pathology in China
      over the past five years, reviews and analyzes the present status of ophthalmic
      pathology in the fields of ophthalmic oncology, orbital diseases and other
      relevant fields. Future developing direction and prospective subjects are raised
      as well.

PMID- 21176615
TI  - [Recent advances in uveitis studies in China].
AB  - Uveitis has become an intensive study area and great achievements have been
      obtained during recent years. Uveitis study team in China has become one of the
      most productive uveitis study groups in the world. Ophthalmologists in China have
      addressed the clinical patterns and characteristics of uveitis in China. Studies
      by Chinese ophthalmologists, for the first time, revealed that IL-23/IL-17 played
      an important role in the pathogenesis of uveitis. Decreased frequency and
      function of CD4+CD25high T cells were shown to be actively involved in the
      development of Vogt-Koyanagi-Harada syndrome. A number of immune-related genes
      were found to be associated with the susceptibility to or resistance against
      Behcet's disease or Vogt-Koyanagi-Harada syndrome. Various molecules, such as Tim
      3 and IDO protein, and Treg cells including CD4+CD25+T, CD4+PD-1+T, CD8+Foxp3+T
      and CD8+CD94+T were found to be involved in the development of anterior chamber
      associated immune deviation, an important mechanism against intraocular
      inflammation. These studies have greatly contributed to the understanding as well
      as the treatment of this disease.

PMID- 21176616
TI  - [Progress of ophthalmic electrophysiology in China in past 5 years].
AB  - The main mission of visual physiology is to elucidate the neuromechanism of
      vision. The basic characters in visual process are the electrochemical changes of
      cell membrane and the active potential which transmits along neuraxon. This
      visual bioelectricity changes can be recorded by using visual stimulus, surface
      electrode and amplified recording apparatus. Clinical electrophysiology
      examination of vision has been an important clinical examination technique in
      ophthalmology. This technique provides a non-traumatic, objective, quantitative
      and location-detecting visual function examination procedure that can inspect
      visual path from the retina to visual cortex. Recently, visual physiology has
      gained noticeable development in basic research and clinical application. This
      article summarizes the development in this field.

PMID- 21176617
TI  - [Recent developments on the scientific research in optometry and visual science
      in China].
AB  - The current text reviewed the situation of the scientific research in the field
      of Optometry and visual sciences in the recent 5 to 6 years in our country. It
      showed the advancement and achievement in the myopic fundamental research and the
      application research of visual science. In addition, it also analyzed the
      guidance of research in solving the clinical visual issues and the significance
      of community service of research in eye care in public. This text indicated by
      the concrete current situation and the result data of research that the biology
      and optics, the double property of the eye endowed the distinguished feature to
      the research in Ophthalmology and Optometry, and that the cross cooperation of
      multidisciplinary promoted the innovation in the fields of Optometry and visual
      research. In future, the fields of Optometry and visual science in China will
      face up to more and more anticipations of the original and systematic research.
      The prophylaxis and treatment of myopia would be still a long-term and rough
      exploration theme in these fields.

PMID- 21176618
TI  - [Present status and development of prevention of blindness and ophthalmic
      epidemiologic studies in China].
AB  - Blindness prevention and ophthalmic epidemiology studies in China have obtained
      greatest progress in the past five years since 2005. For example, the secondary
      sampling epidemiologic study of disabled persons in China in 2006 showed that the
      major causes of blindness and vision impairment were cataract (56.7%), retinal
      and uveal diseases (14.1%) and corneal diseases (10.3%). Important blindness
      prevention projects, such as "Sight first, China action" stage II project and
      "Free cataract surgeries for one million poor patients" project, have achieved
      their goals. From 2005 to 2009, 3.871 millions of cataract surgeries were
      performed in China, and the cataract surgical rate increased to 796.2 per million
      population in 2009. Cataract surgery obstacle-free areas have been built in 673
      counties, 70 cities and 2 provinces since 2007. The visual performance of 175,501
      low-vision patients have been improved by low-vision aids, and 47,009 blind
      persons have been offered walk mobility training course. Furthermore,
      achievements and progress have been obtained in primary eye care, prevention and
      treatment for trachoma, childhood eye diseases and diabetic retinopathy. These
      results has met the requirements established by Chinese government, but has not
      reached the goal of "Vision 2020". Certain problems still exist in China,
      including low cataract surgical rate, major avoidable blinding diseases not
      eliminated, and lack of innovative and profound epidemiological studies. Future
      Chinese ophthalmic epidemiology studies may focus on original investigation and
      molecular research. In order to realize the goal of "Vision 2020" and eliminate
      avoidable cataract blindness, all kinds of eye care services should be
      integrated, and various prevention and treatment strategies with low cost and
      superior quality for cataract, retinal diseases, corneal diseases, trachoma,
      refractive error, low vision, and glaucoma should be used.

PMID- 21176619
TI  - [A citation analysis of Chinese Journal of Ophthalmology from 2005 to 2009].
AB  - OBJECTIVE: To evaluate the academic level and the quality of Chinese Journal of
      Ophthalmology (CJO) by analyzing its citation status. METHODS: Bibliometrics was
      used to analyze and evaluate the distribution of original papers in CJO in 2005
      2009 based on the data of Chinese Medical Citation Index (CMCI). RESULTS: A total
      of 1358 papers were published in CJO between 2005 and 2009. Among them, 695 were
      cited for 2333 times, with an average of 3.36 times per cited paper. The papers
      were cited by authors from 26 provinces or municipalities or autonomous regions,
      Hongkong and Macao, China, as well as 2 from United States. The regions from
      where the papers had the highest citation were Beijing (202 times), Shanghai
      (93), Guangdong (82) and Shandong (69). The institutions with the highest
      citation rates were Zhongshan Ophthalmic Center of Sun Yat-Sen University (349
      times) and Beijing Tongren Eye Center (265). CJO had been cited by more than 300
      other journals in the past 5 years, such as International Ophthalmology,
      Ophthalmology and Chinese Journal of Practical Ophthalmology. CONCLUSIONS: CJO,
      which is the journal with the high quality and citation rate, is one of the
      resources with important information in ophthalmology. It is one of the
      prestigious medical journals in China.

PMID- 21176620
TI  - [To inherit the fine tradition for the development of Chinese Journal of
      Ophthalmology].

PMID- 21176621
TI  - [My dedication to the innovation and development of Chinese Journal of
      Ophthalmology].

PMID- 21176622
TI  - [Thoughts and feelings on my editing life].

PMID- 21176623
TI  - [Chinese Journal of Ophthalmology and me].

PMID- 21176625
TI  - [A review of the development of Chinese Journal of Ophthalmology from my
      collections].

PMID- 21176624
TI  - [Thoughts and impressions during the sixty year anniversary of Chinese Journal of
      Ophthalmology].

PMID- 21176626
TI  - [Outcome of patients with non-ST segment elevation acute coronary syndrome
      undergoing early or delayed intervention].
AB  - OBJECTIVE: To compare the effect and safety of early intervention and delayed
      intervention in patients with non-ST segment elevation acute coronary syndrome.
      METHODS: In this multicenter randomized trial, patients diagnosed as non-ST
      segment elevation acute coronary syndrome were randomly assigned to undergo early
      intervention (coronary angiography <= 24 hours after randomization, n = 446) or
      delayed intervention (coronary angiography >= 36 hours after randomization, n =
      369). The primary outcome was a composite of death, myocardial infarction or
      stroke at 180 days. The secondary outcome was death, myocardial infarction,
      refractory ischemia, stroke or revascularization at 180 days. RESULTS: Baseline
      clinical characteristics were comparable between the two groups. Incidence of
      both primary (9.0% vs. 14.6%, P = 0.01) and secondary which was a composite of
      death, myocardial infarction or refractory ischemia (14.6% vs. 22.0% P = 0.01)
      endpoints were significantly lower in early intervention group than in delayed
      intervention group. Incidence of myocardial infarction was significantly lower in
      early intervention group than in delayed intervention group (5.2% vs. 10.8%, P =
      0.00). Another secondary outcome which was a composite of death, myocardial
      infarction, refractory ischemia, stroke or revascularization was similar between
      the two groups (26.7% vs. 30.4%, P = 0.25). CONCLUSION: Compared to delayed
      intervention group, early intervention reduced incidence of myocardial infarction
      but did not affect the incidence of death, stroke or refractory ischemia in
      patients with non-ST segment elevation acute coronary syndrome.

PMID- 21176627
TI  - [Effect of percutaneous coronary intervention timing and cilostazol use on left
      ventricular remodeling in patients with non-ST elevation myocardial infarction].
AB  - OBJECTIVE: To observe the dynamic changes of plasma matrix metalloproteinases
      (MMPs) and investigate the effect of early or delayed percutaneous coronary
      intervention (PCI) in the presence or absence cilostazol on left ventricle (LV)
      remodeling in patients with non-ST elevation myocardial infarction (NSTEMI).
      METHODS: One hundred and sixty-four patients undergoing PCI with NSTEMI were
      randomized to early PCI (PCI within 24 h) group or delayed PCI group (PCI after
      36 h), and patients in both group were further assigned to cilostazol or no
      cilostazol group. Plasma MMP-2 and MMP-9 concentrations were measured at 2, 4
      days and 2 and 4 weeks after PCI. Left ventricular end-diastolic volume (LVEDV),
      left ventricle ejection fraction (LVEF), left ventricle posterior wall (LVPW) and
      interventricular septum (IVS) were measured by echocardiography at baseline and 1
      year after PCI. RESULTS: MMP-2 concentration at 2 weeks after PCI is higher than
      that at 2, 4 days and 4 weeks after PCI. MMP-9 concentration at 4 days is higher
      than that at 2 days, 2 weeks and 4 weeks after PCI. MMP-2 and MMP-9 were
      significantly lower in cilostazol group compared with that in non-cilostazol
      group at 4 days, 2 weeks and 4 weeks after NSTEMI (all P < 0.05). Changes of
      LVEDV and LVEF were significantly less in cilostazol group and early PCI group
      than that in no cilostazol group and delay PCI group (P < 0.05 or P < 0.01) at 1
      year after NSTEMI. CONCLUSIONS: Early PCI and Cilostazol use are associated with
      less LV remodeling in patients with NSTEMI. Cilostazol attenuated LV remodeling
      possibly by reducing concentration of MMP-2 and MMP-9 after PCI.

PMID- 21176628
TI  - [Outcome of patients with ST-elevation myocardial infarction complicated by pre
      hospital cardiac arrest underwent emergency percutaneous coronary intervention].
AB  - OBJECTIVE: To evaluate the outcome of ST-elevation acute myocardial infarction
      (STEMI) patients complicated pre-hospital cardiac arrest underwent percutaneous
      coronary intervention (PCI). METHODS: From September 2004 to November 2008, 1446
      consecutive patients with acute STEMI underwent PCI in our department. 49 out of
      1446 patients complicated by pre-hospital cardiac arrest. Clinical outcome
      including total mortality, adverse cardiac events, stroke and bleeding events
      during the hospitalization period and within 1 year after discharge was compared
      between patients with or without pre-hospital cardiac arrest. RESULTS: PCI
      success rate was similar (85.7% vs. 88.8%, P = 0.497) while the incidence of in
      hospital cardiogenic shock 22.4% vs. 3.0%, P < 0.001 and cardiac arrest (44.9%
      vs. 5.9%, P < 0.001) and in-hospital mortality (36.7% vs. 2.0%, P < 0.001) were
      significantly higher in patients with pre-hospital cardiac arrest than patients
      without pre-hospital cardiac arrest. Time from symptom onset to emergency
      treatment, asystole as initial rhythm, Glasgow coma scale (GCS <= 7) and
      cardiogenic shock on admission were independent risk factors of in-hospital death
      in patients with pre-hospital cardiac arrest. During follow up, incidences of
      overall mortality, re-infarction, revascularization and stroke were similar
      between the two groups. CONCLUSIONS: STEMI patients with pre-hospital cardiac
      arrest undergoing emergency PCI are facing higher risk of cardiogenic shock and
      cardiac arrest and higher in-hospital mortality compared to those without pre
      hospital cardiac arrest. However, the post-hospital discharge outcome was similar
      between the two groups.

PMID- 21176629
TI  - [Efficiency and safety of thrombus aspiration plus intra-infarct-related artery
      administration of tirofiban during primary angioplasty].
AB  - OBJECTIVE: To investigate whether thrombus aspiration plus intra-infarct-related
      artery bolus administration of tirofiban via the aspiration catheter is superior
      to thrombus aspiration alone in improving myocardial perfusion in patients with
      ST-elevation myocardial infarction (STEMI) undergoing primary angioplasty.
      METHODS: In this single center retrospective study, 108 patients with STEMI who
      underwent angioplasty after thrombus aspiration plus intra-infarction related
      artery 500 ug tirofiban administration, with subsequent 12-hour intravenous
      infusion of 0.1 ug*kg(-1)*min(-1) after angioplasty (thrombus aspiration +
      tirofiban group) and 108 matched control patients with STEMI who underwent
      angioplasty after thrombus aspiration (thrombus aspiration group). The primary
      end points included thrombolysis in myocardial infarction (TIMI) flow immediately
      after angioplasty, complete ST-segment elevation resolution (> 70%) at 90 minutes
      after angioplasty and the peak of creatine kinase-MB (CK-MB) and troponin I
      (TnI). The secondary end points were the left ventricular ejection fraction
      (LVEF) in the hospital and at 9 months follow-up as well as major adverse cardiac
      events (MACE: cardiac death, target vessel revascularization, re-infarction) at 9
      months and any bleeding events. RESULTS: Baseline characteristics of the two
      groups were well-balanced. The TIMI 3 flow rate (97.22% vs. 87.04%, P = 0.011)
      and the complete ST-segment resolution rate (66.67% vs. 50.91%, chi(2) = 6.129, P
      = 0.047)were significantly higher in the thrombus aspiration + tirofiban group
      than in the thrombus aspiration group. The peak of CK-MB (83.9 U/L vs. 126.1 U/L,
      P = 0.034) and TnI (42.7 ng/ml vs. 72.5 ng/ml, P = 0.029) were significantly
      lower in the thrombus aspiration + tirofiban group than in the thrombus
      aspiration group. LVEF in the hospital favored thrombus aspiration + tirofiban
      the group (45.7% +/- 10.8%, 42.9% +/- 9.9%, t = 1.99, P = 0.049). There was a
      tendency to decreased MACE rate at 9-month follow-up, which favored thrombus
      aspiration + tirofiban the group (logrank chi(2) = 2.865, P = 0.09). Bleeding
      events were similar between the two groups. CONCLUSION: Thrombus aspiration plus
      intra-infarct-related artery bolus administration of tirofiban in patients with
      STEMI undergoing primary angioplasty may improve myocardium perfusion, attenuate
      myocardial ischemia and result in a better clinical prognosis compared to
      thrombus aspiration alone.

PMID- 21176630
TI  - [Efficacy comparison of primary percutaneous coronary intervention with
      biodegradable polymer- and durable polymer-based sirolimus-eluting stents for
      patients with acute myocardial infarction].
AB  - OBJECTIVE: This prospective random control study was performed to compare the
      efficacy and safety of primary percutaneous coronary intervention (PCI) with
      biodegradable polymer (Excel) and with durable polymer (Cypher Select) sirolimus
      eluting stents in patients with acute ST-elevation myocardial infarction (STEMI).
      METHODS: Consecutive patients with STEMI underwent primary PCI were randomly
      divided into Cypher group (n = 113) and Excel group (n = 115). The primary
      endpoints were major adverse cardiac events (MACE, including death, reinfarction
      and target vessel revascularization) within 12 months. The second endpoints
      included late luminal loss and restenosis at 9 months. RESULTS: Angiographic
      follow-up data at 9 months were available in 43 (38%) patients in Cypher group
      and 48 (42%) in Excel group. The rates of in-stent restenosis and in-segment
      restenosis were 2.3% vs. 2.1% (P = 0.937) and 4.7% vs. 6.3% (P = 0.738),
      respectively. The late luminal loss of in-stent and in-segment were (0.17 +/-
      0.26) mm vs. (0.18 +/- 0.33) mm (P = 0.483) and (0.19 +/- 0.36) mm vs. (0.20 +/-
      0.42) mm (P = 0.419), respectively. There were no significant differences in
      death (3.5% vs. 2.6%, P = 0.692), reinfarction (1.8% vs. 2.6%, P = 0.658), target
      vessel revascularization (1.8% vs. 2.6%, P = 0.658), MACE (5.3% vs. 6.1%, P =
      0.788) or stent thrombosis (4.4% vs. 3.5%, P = 0.692) at 12 months between Cyper
      group and Excel group. CONCLUSIONS: Excel and Cypher Select stents may have
      similar mid-term efficacy and safety in patients with STEMI treated with primary
      PCI.Further investigation is warranted to validate the long-term efficacy and
      safety.

PMID- 21176631
TI  - [Ischemic J wave changes before and post percutaneous coronary intervention in
      patients with coronary artery disease].
AB  - OBJECTIVE: To observe the incidence of ischemic J wave before and post
      percutaneous coronary intervention (PCI) in patients with coronary heart disease
      (CHD). METHODS: CHD patients (n = 117) underwent percutaneous coronary
      intervention (PCI) in Shanxi cardiovascular hospital were included in this study.
      The 12-lead ECGs were recorded within 24 hours before and after PCI. The ischemic
      J waves of five lead-groups (II, III, aVF group: V(1), V(2) group; V(3), V(4)
      group; V(5), V(6) group;I, aVL group) were analyzed and the number of lead-groups
      with J waves (0 - 5) were obtained in each patient. According to time course or
      wave amplitude, J waves were classified into three grades: small (time course
      between 0.02 - 0.03 s or wave amplitude between 0.05 - 0.09 mV), large (time
      course between 0.04 - 0.06 s or wave amplitude between 0.10 - 0.20 mV) and
      enormous (time course > 0.06 s or wave amplitude > 0.20 mV) J waves. RESULTS: The
      number of lead-groups with ischemic J waves (0 - 5) in each patient was similar
      between pre and post PCI in the 117 patients (chi(2) = 6.23, P = 0.285). The
      numbers of small, large and enormous J waves were 157, 36 and 9 respectively
      before PCI and 163, 20 and 5 after PCI. The incidence of small J waves increased
      (77.72% vs. 86.70%) while large and enormous J waves decreased (17.82%, 4.46% vs.
      10.64%, 2.66%) post PCI (chi(2) = 5.28, P < 0.05). CONCLUSIONS: The numbers of
      lead-groups with ischemic J waves were similar before and post PCI. However, the
      amplitude of ischemic J waves decreased after PCI suggesting PCI could improve
      ischemic J waves in CHD patients.

PMID- 21176632
TI  - [Incidence and causes of nonresponse to cardiac resynchronization therapy in
      patients with congestive heart failure].
AB  - OBJECTIVE: To observe the incidence and explore the potential factors of
      nonresponse to cardiac resynchronization therapy(CRT)in patients with severe
      chronic congestive heart failure. METHOD: CRT was performed in 119 patients with
      NYHA function class III-IV and left ventricular ejection fraction <= 35% [96 men
      and 23 women, age (60.5 +/- 11.3) years]. RESULTS: Seven patients died for
      different reasons between 1 - 6 months post CRT and clinical and
      echocardiographic (Echo) data at 6 months post CRT were analyzed from the
      remaining 112 patients. The incidence of nonresponse to CRT was 28.57%. Compared
      to the response group, complete right bundle branch block, longer course of
      congestive heart failure, higher pulmonary systolic pressure and serum creatinine
      level and non-optimal target vessels positioning of the left ventricle lead (the
      great cardiac vein and the middle cardiac vein) were the independent predictors
      for nonresponse after CRT (all P < 0.05). Compared with nonresponse group, the
      dosages of digoxin and diuretics used for heart failure were significantly
      reduced in response group (P < 0.01). CONCLUSIONS: The incidence of nonresponse
      after CRT was 28.57% in this patient cohort. Higher pulmonary systolic pressure
      and serum creatinine level and non-optimal target vessels positioning of the left
      ventricle lead (the great cardiac vein and the middle cardiac vein) were the
      independent predictors for nonresponse after CRT.

PMID- 21176633
TI  - [Chinese risk stratification scoring system for coronary artery bypass grafting].
AB  - OBJECTIVE: To construct a scoring system for the prediction of in-hospital
      mortality in Chinese patients undergoing coronary artery bypass grafting (CABG).
      METHODS: From 2007 to 2008, complete clinical information of 9564 consecutive
      CABG patients was collected from Chinese coronary artery bypass grafting registry
      which recruited patients from 43 Chinese centers. This database was randomly
      divided into developmental and validation subsets (9:1). A risk model was
      developed using logistic regression. Calibration and discrimination
      characteristics were assessed in the validation dataset. Thresholds were defined
      for each model to distinguish different risk groups. The risk model was compared
      with EuroSCORE system in the validation dataset. RESULTS: In the developmental
      dataset, calibration by Hosmer-Lemeshow (HL) test was P = 0.44 and discrimination
      by area under ROC (AUC) was 0.80. In the validation dataset, HL test was P =
      0.34, AUC was 0.78. The performance turned out good for all three risk groups.
      Superiority were found over EuroSCORE (HL P = 0.60; AUC 0.73). The scoring system
      identified 11 risk factors (with weights in brackets): age over 65 (65 - 69, 3;
      70 - 74, 5; over 75, 6), preoperative NYHA stage (NHYA III, 3; NHYA IV, 7),
      chronic renal failure (6), extracardiac arteriopathy (5), chronic obstructive
      pulmonary disease (4), Preoperative atrial fibrillation or flutter (within two
      weeks) (2), left ventricular ejection fraction < 50% (4), other than elective
      surgery (5), combined valve procedure (4), preoperative critical state (4), BMI
      (> 24 kg/m(2), -2; < 18 kg/m(2), 5). CONCLUSION: This study constructs a simple,
      objective and accurate risk stratification system for Chinese patients undergoing
      CABG using the most up-to-date data.

PMID- 21176634
TI  - [Cardiovascular manifestations in Chinese patients with hypereosinophilic
      syndrome].
AB  - OBJECTIVE: To evaluate the cardiovascular involvements in Chinese patients with
      hypereosinophilic syndrome. METHOD: We respectively reviewed 149 inpatients with
      hypereosinophilic syndrome admitted to Peking Union Medical College Hospital and
      analyzed the cardiovascular involvements in these patients. RESULTS: Cardiac
      abnormalities was evidenced in 32.9% patients (49/149). The ratio of male vs
      female was 34:15. The average age of the patients was (41.3 +/- 16.9) years and
      course of disease was (26.4 +/- 72.3) months. Cardiovascular involvements
      included ST segment and/or T wave (ST-T) ischemic changes, arrhythmia, myocardial
      injury, cardiac thrombosis, pericardial effusion, pulmonary hypertension, valve
      disorder, vein or artery thrombosis. After glucocorticoid and/or chemotherapeutic
      agents and treatment for symptoms, 11 (22.4%) patients achieved remission but
      have recurrent attacks and 3 (6.1%) patients died from failure in treatment. The
      prognosis in patients with echocardiogram abnormalities were poorer than those
      only with electrocardiogram abnormalities (P < 0.05). CONCLUSIONS: Cardiovascular
      involvements are common in patients with hypereosinophilic syndrome and the
      manifestation of these involvement is various. Cardiovascular complications of
      HES are a major source of morbidity and mortality in these disorders.

PMID- 21176635
TI  - [Diagnostic value of 64-slice spiral computed tomography coronary angiography for
      coronary artery disease].
AB  - OBJECTIVE: To assess the diagnostic accuracy of 64-slice computed tomography
      coronary angiography (64-SCTCA) in individuals with suspected coronary artery
      disease (CAD). METHODS: The study enrolled 285 individuals undergoing 64-SCTCA
      with calcium scoring and thereafter invasive coronary angiography (CAG) within 4
      weeks for suspected CAD. Pretest probability of having obstructive CAD was
      determined using the Duke clinical score, which was estimated by type of chest
      discomfort, age, gender, and traditional risk factors and stratified into 3
      levels of probability: low (<= 30%, n = 80), intermediate (31% to 70%, n = 92),
      and high (>= 71%, n = 113). CAD was defined as the presence of at least one
      vessel of >= 50% coronary stenosis on CAG. RESULTS: The patient-based diagnostic
      accuracy of 64-SCTCA for detecting CAD according to CAG revealed a sensitivity of
      81.2%, a specificity of 93.3%, a positive predictive value of 68.0% and negative
      predictive value of 96.6%. The CAD prevalence in the low, intermediate and high
      risk groups according to Duke probability was 46.3%, 72.8% and 82.3%,
      respectively. The sensitivity and positive predictive value were lower in the low
      probability group than those in the intermediate and high probability groups. For
      those with coronary artery Agatston calcium score > 400, the diagnostic accuracy
      was linked with a higher sensitivity but lower specificity. The diagnostic value
      of 64-SCTCA for proximal and mid-segment of coronary artery was superior to that
      for distal segment. CONCLUSIONS: 64-SCTCA is mainly indicated in individuals with
      an intermediate probability of having CAD. The diagnostic value of 64-SCTCA could
      be affected by coronary artery calcium, lesion location and vessel diameter.

PMID- 21176636
TI  - [Reasons for failed electrocardiographic identification of the infarct-related
      artery in patients with ST-elevation acute myocardial infarction].
AB  - OBJECTIVE: The infarct-related artery (IRA) could not always be identified by
      electrocardiogram (ECG). In the present study, we attempted to explore the reason
      for failed IRA identification by ECG based on the comparison between ECG records
      and coronary angiographic findings. METHODS: All 18-lead ECG records were
      compared with respective angiographic findings in 1024 consecutive patients with
      ST elevation myocardial infarction (STEMI) between October 2004 and July 2009.
      More than two continuous 18-lead ECG records were performed within 12 hours of
      the symptom onset in all patients. Patients with previous myocardial infarction,
      coronary artery bypass surgery, pacemaker implantation or ECG evidence of left
      bundle branch block and angiography was performed more than 12 hours time from
      symptom onset were excluded. RESULTS: Of all 1024 patients enrolled, the IRA were
      correctly identified in 854 cases and identified wrong in 96 cases and could not
      be identified in 74 cases by ECG. Of the failed identification in these 170
      cases, IRA was left circumflex coronary artery in 76 (44.7%)cases, right coronary
      artery in 66 (38.8%) cases, left anterior descending branch in 20 (11.8%) cases,
      ramus medianus branch in 7 (4.1%) cases, and left main in 1(0.6%) case. Double
      vessel and triple-vessel diseases were recorded in 27(15.9%) patients and
      47(27.6%) patients respectively. Early repolarization syndrome occurred in 8
      (4.7%) patients, and dextrocardia in 1 patient (0.6%). Angiographic study showed
      acute occlusion of a small branch in 6 (3.5%) patients. CONCLUSION: Coronary
      collateral vessel can mislead judgments of the IRA by ECG. When the IRA can not
      be determined by ECG, left circumflex coronary artery is most likely to be the
      culprit vessel. Occasionally, early repolarization syndrome and anatomic
      variation of the coronary artery or heart and a small branch occlusion could be
      causes of misjudgments of IRA by ECG.

PMID- 21176637
TI  - [Association between rs4149601 polymorphism and essential hypertension in
      Kazakh].
AB  - OBJECTIVE: To investigate the association between a functional rs4149601
      polymorphism of neural precursor cell expressed developmentally downregulated 4
      like gene (NEDD4L) and essential hypertension in Kazakh. METHODS: In this
      population-based association study, the genotypes of rs4149601 polymorphism were
      identified by TaqMan PCR in 883 subjects (male 375 383 hypertensives) and its
      distribution and relationship to hypertension were studied. The association
      between haplotype (rs4149601, 296921-296923delTTG, rs2288774 and rs2288775, the
      last three polymorphisms are representative variations identified from 94 Kazakh
      hypertensive individuals by screening the functional region of NEDD4L previously)
      and hypertension was also investigated. RESULTS: The genotype distribution of
      rs4149601 polymorphism was in Hardy-Weinberg equilibrium. The genotype
      distribution of rs4149601 polymorphism was similar between the essential
      hypertension patients and the control individuals (all P > 0.05). In the
      haplotype-based case-control analysis, the distribution of the haplotypes was not
      significantly different between the case and the control individuals in total and
      in male subjects but the frequency of D-C-G-G (296921
      3delTTG/rs2288774/rs2288775/rs4149601) haplotype was significantly higher in
      hypertensive than in control individuals in female (P = 0.026). CONCLUSION: Our
      results suggested that D-C-G-G haplotype of NEDD4L but not rs4149601 polymorphism
      was linked with hypertension in Kazakh.

PMID- 21176638
TI  - [Simvastatin suppress lipopolysaccharides induced upregulation of lipoprotein
      associated phospholipase A(2) expression in macrophages via inactivation of
      p38MAPK pathway].
AB  - OBJECTIVE: To investigate the effects of simvastatin on lipopolysaccharides (LPS)
      induced upregulation of Lp-PLA(2) in human peripheral blood monocytes-macrophages
      and the related mechanisms. METHODS: Peripheral blood monocytes of healthy
      volunteer were isolated and incubated for 2-3 days. Monocytes were incubated with
      various concentrations of LPS for 6 h or with 1 ug/ml of LPS for different times
      in LPS group. In simvastatin group and MAPK inhibitors groups, cells were pre
      treated with simvastatin (10(-2) - 10(-7) mmol/L) or various MAPK inhibitors (10
      umol/L SB203580, 20 umol/L U0126, and 20 umol/L SP600125) before LPS co
      incubation. Lp-PLA(2) activity was measured by chronometry, Lp-PLA(2) mRNA
      expression was detected by RT-PCR. Protein expressions of Lp-PLA(2) and p38MAPK
      and phosphorylated p38MAPK were examined by Western blot. RESULTS: (1) LPS
      significantly upregulated Lp-PLA(2) mRNA and protein expression, as well as the
      enzyme activity in a time and concentration dependent manner, which could be
      significantly attenuated by simvastatin in a time and concentration dependent
      manner. (2) Simvastatin significantly reduced LPS-induced p38MAPK
      phosphorylation. The p38 MAPK inhibitor SB203580, but not MEK1/2 inhibitor U0126
      and JNK inhibitor SP600125, completely prevented LPS-mediated up-regulation of Lp
      PLA(2) at protein level. CONCLUSION: This study demonstrated that LPS
      significantly upregulated Lp-PLA(2) mRNA and protein expression, as well as the
      enzyme activity in a time and concentration dependent manner via Rho-p38MAPK
      pathway, which could be significantly suppressed by simvastatin.

PMID- 21176639
TI  - [Ischemia preconditioning attenuated myocardial ischemia via upregulating the
      expression of adiponectin in rat].
AB  - OBJECTIVE: To investigate whether adiponectin plays a role in the protection of
      myocardium in the rat myocardial ischemia preconditioning (IPC) model. METHOD:
      Infarct size was measured by Masson's Trichrome staining, the expression of
      protein and mRNA of adiponectin at 0, 6, 12 and 24 h after IPC was examined by
      immunohistochemistry and quantitative real time RT-PCR, plasma levels of
      adiponectin at above mentioned four time points after IPC were detected by ELISA
      in IPC and MI rats. RESULT: Infarct size was smaller in IPC than in MI rats (20%
      +/- 2% vs. 31% +/- 3%, P < 0.05). The expression of adiponectin mRNA at 6 h and
      12 h after IPC was 2.2 and 2.1 times higher than in Sham rats at respective time
      points (P < 0.05). Immunohistochemistry staining evidenced increased adiponectin
      expression in the ischemic area and weak expression of adiponectin in non
      ischemic area (P < 0.05). Compared to the sham group, the plasma level of
      adiponectin increased significantly at 0, 6 and 12 h after IPC (0 h: 7.40 +/-
      0.47 vs. 10.90 +/- 1.74; 6 h: 8.18 +/- 1.41 vs. 10.98 +/- 1.74; 12 h: 6.97 +/-
      1.02 vs. 9.31 +/- 0.96, P < 0.05). CONCLUSION: IPC reduced infarction size,
      upregulated the myocardial expression of adiponectin at mRNA and protein levels,
      and increased plasma adiponectin concentration, suggesting that the adiponectin
      may play a critical role in the protective effect of IPC.

PMID- 21176640
TI  - [Relationship between serum non-high-density lipoprotein cholesterol and
      incidence of cardiovascular disease].
AB  - OBJECTIVE: To evaluate the relationship between serum non-HDL-C and incidence of
      various cardiovascular disease (CVD) in Chinese population aged 35-64 years.
      METHODS: This prospective study was performed from 1992 to 2004 in 11 provinces
      of China and the association between baseline non-HDL-C level with the risk of
      various CVD events was analyzed in 29 937 subjects aged 35-64 years using Cox
      multivariate proportional hazards regression. CVD events in this study including
      acute coronary events (ACE), ischemic stroke, hemorrhagic stroke and ischemic
      cardiovascular disease (ICVD). RESULTS: (1) Adjusted for age, gender, smoking
      status, diabetes, body mass index and blood pressure, the relative risk of ACE,
      ischemic stroke and ICVD in groups of non-HDL-C 3.37 - 4.13 mmol/L (130 - 159
      mg/dl), 4.14 - 4.91 mmol/L (160 - 189 mg/dl) and >= 4.92 mmol/L (190 mg/dl) was
      1.24 (0.91 - 1.70), 1.78 (1.25 - 2.53), 2.23 (1.48 - 3.35); 1.34 (1.07 - 1.68),
      1.38 (1.04 - 1.83), 1.38 (0.97 - 1.94) and 1.37 (1.12 - 1.63), 1.52 (1.22 -
      1.90), 1.70 (1.30 - 2.22), respectively. The risk of hemorrhagic stroke was
      declined obviously in group > 4.92 mmol/L (190 mg/dl). (2) The correlation
      between VLDL-C and ACE was the strongest in four CVD events when VLDL-C and LDL-C
      were joint analyzed, ICVD events ranked the second. The risk for ischemic stroke
      also borderline increased with increasing VLDL-C and LDL-C (P > 0.05).
      CONCLUSION: Increased non-HDL-C is associated with increased risk of suffering
      ACE, ischemic stroke and ICVD and VLDL-C plays a critical role in the development
      of ICVD events, especially ACS, in middle aged Chinese population.

PMID- 21176641
TI  - [Etiology analysis for hospitalized hypertensive patients: 10 years report from
      the department of hypertension (1999 - 2008)].
AB  - OBJECTIVE: To analyze etiology of hospitalized hypertensive patients in the
      department of hypertension from 1999 to 2008. METHODS: This retrospective study
      was performed to analyze the etiology of hospitalized hypertensive patients in
      department of hypertension and to show the distribution change of hypertension
      from 1999 to 2008. RESULTS: (1) There were 5867 (75.1%) patients with essential
      hypertension and 1942 (24.9%) patients with secondary hypertension (SH). (2) The
      prevalence rate of SH increased significantly during the 10 years (chi(2) =
      387.621, P < 0.001) and was higher in 2008 than in 1999 (39.3% vs. 9.5%, P <
      0.05). The prevalence of obstructive sleep apnea syndrome (OSAS) and primary
      aldosteronism (PA) in 2008 increased 38.3 and 1.8 times respectively than in 1999
      (chi(2) = 304.025, P < 0.001; chi(2) = 42.845, P < 0.001) and other SH remained
      unchanged. (3) The prevalence of PA complicated with OSAS increased significantly
      in recent five years (chi(2) = 26.376, P < 0.001). Incidence of OSAS was 23.9% in
      PA patients and incidence of PA was 6.7% in OSAS patients. CONCLUSIONS: With the
      insights gained on hypertension mechanism and the development of new diagnostic
      technology, percent of diagnosed SH increased remarkably in recent years in
      hospitalized hypertensive patients in our department of hypertension. OSAS and PA
      are the leading causes of SH.

PMID- 21176642
TI  - [A cross-racial analysis on the susceptible gene polymorphisms of salt-sensitive
      hypertension].
AB  - OBJECTIVE: To compare the genetic distributions of salt-sensitivity of four
      ethnic populations in Hapmap database. METHODS: The frequencies data (395
      subjects) of salt-sensitivity polymorphisms (AGT/M235T, ACE/ID, CYP11B2/C-344T,
      ADDI/Gly460Trp, GNB3/C825 and CYP3A5/A6986G)of Utah residents with ancestry from
      northern and western Europe (CEU), Han Chinese in Beijing (CHB), Japanese in
      Tokyo (JPT) and Yoruba mother-father-child trios in Ibadan, Nigeria (YRI) were
      obtained from International HapMap Project. The good-fit chi(2) test was
      performed to test whether the frequencies of each genotype reached Hardy-Weinberg
      equilibrium. The differences of the genotype and allele distribution and trend
      analysis were detected via chi(2) test. Furthermore, multiple comparisons between
      two populations were analyzed by Lancaster's partition of chi-squares. RESULTS:
      There were significant differences of each genotype distribution among four
      ethnic populations (P < 0.05). The distribution of genotype frequencies and
      susceptible allele frequencies of salt sensitive candidate genes were similar
      between CHB and JPT. Excepted for GNB3/825T allele (38.8% vs.34.4%, P = 0.521),
      susceptible allele frequencies in AGT/235T (79.2% vs. 41.2%, P < 0.001), ACE/I
      (56.5% vs. 43.5%, P < 0.001), CYP11B2/-344T (74.1% vs. 56.7%, P = 0.001),
      ADDI/460Trp (51.8% vs. 20.4%, P < 0.001) and CYP3A5/A6986 (30.1% vs. 3.6%, P <
      0.001) were significantly higher in CHB than in CEU. There distribution of
      ADDI/460Trp allele was significant lower in YRI (4%) than in CHB (51.8%, P <
      0.001). However frequencies of AGT/235T, CYP11B2/-334T, GNB3/825T and
      CYP3A5/6986A in CHB were significantly lower than those in YRI (P < 0.05). Trend
      analyses showed significantly increased trend in AGT/235T (41.2% < 79.2% < 92.0%,
      P < 0.001), CYP11B2/-334T (56.7% < 74.1% < 84.8%, P < 0.001) and CYP3A5/6986A
      (3.6% < 30.1% < 84.5%, P < 0.001) in CEU, CHB and YRI. CONCLUSIONS: There are
      significant discrepancy of salt-sensitivity variant distributions among four
      ethnic populations in Hapmap database. The frequencies of the susceptible
      polymorphisms related to salt-sensitivity in Beijing Han population was similar
      with JPT, higher than in CEU but lower than in YRI, suggesting high salt
      sensitive and risk for hypertension in Beijing Han population. Prevention and
      individual therapy for high-risk population will help to reduce the prevalence of
      salt-sensitive hypertension and cardiovascular diseases.

PMID- 21176643
TI  - [Case reports of atrial septal defect and left superior pulmonary venous drainage
      in 2 patients].

PMID- 21176644
TI  - [Interaction between clopidogrel and proton pump inhibitors].

PMID- 21176645
TI  - [The mechanisms and the role of statins in treating pulmonary hypertension].

PMID- 21176646
TI  - [Association between increased total cholesterol content of erythrocyte membranes
      levels and acute coronary syndrome].

PMID- 21176647
TI  - [The state-of-the art in minimally invasive neurosurgery].

PMID- 21176648
TI  - [Pure endoscopic endonasal transsphenoidal approach for 375 pituitary adenomas].
AB  - OBJECTIVE: To describe the experience with surgical treatment of pituitary
      adenomas via a fully transnasal endoscopic approach. METHODS: Clinical records of
      375 cases with pituitary adenomas underwent pure endoscopic operations between
      December 2006 and December 2009 were carefully assembled. Among 375 pure
      endoscopic operations of pituitary adenomas, 201 cases were nonfunctional
      adenomas and 174 cases were functional adenomas. There were 27 giant pituitary
      adenomas (7.2%) and 41 pituitary adenoma invaded cavernous sinus (10.9%).
      Intraoperative 1.5 T MRI and neuro-navigation system were used during some
      operations. The postoperative and follow-up data of patients were analyzed.
      RESULTS: There were 234 (79.3%) cases of total resection, 56 (19.0%) cases of
      subtotal resection, 5 (1.7%) cases of partial resection. Sixty-eight patients had
      vision improved in 73 patients with vision decreasing before operation. Sixty
      eight (77.3%) patients got normal endocrine in 88 hyper-prolactin patient. Fifty
      five (84.1%) patients got normal growth hormone in 63 patients with
      somatotrophinomas. Eighteen (78.2%) patients got normal in 23 patients with
      corticotrophinoma. These was no death case in this group. One case (0.3%)
      suffered post-operative coma. Transient decreasing of vision occurred in 2 cases
      (0.5%). Transient palsy of oculomotor nerve or abducens nerve occurred in 7 cases
      of operations involved cavernous sinus. Three (0.8%) patients had cerebral
      meningitis. Two patients (0.5%) suffered from cerebrospinal fluid leak but none
      underwent operation to repair. Fourteen patients (3.7%) had transient diabetes
      insipidus. Six patients (1.6%) had nose bleeding. CONCLUSIONS: Trans-nasal
      endoscopy provides a new device for operation of pituitary adenomas which is
      effective and safe. Comparing with microscope, endoscopic visual field is
      clearer, closer and wider.

PMID- 21176649
TI  - [Endoscopic treatment of middle fossa arachnoid cysts].
AB  - OBJECTIVE: To investigate and evaluate the effectiveness of neuroendoscopic
      therapy for arachnoid cysts of middle cranial fossa. METHODS: From January 2004
      to June 2009, 32 patients with arachnoid cysts of middle cranial fossa who were
      treated with endoscopic cystocisternal fenestration were retrospectively
      analyzed. There were 21 male patients and 11 female patients, aged from 6 months
      to 39 years. The clinical and neuroradiological presentation, indications,
      surgical technique, complications, and clinical and neuroradiological follow-up
      were analyzed. RESULTS: The cysts were reduced in size in 20 patients and
      completely disappeared in 4 patients. For the 27 patients with symptoms before
      operation, the symptoms disappeared in 8 cases and improved in 17 cases after
      operation. There were asymptomatic subdural hydroma in 4 patients, intracranial
      infection and incision cerebro-spinal fluid leakage in 1 patient respectively.
      The complication incidence rate was 18.8%. CONCLUSIONS: Endoscopic fenestration
      is an effective treatment for symptomatic arachnoid cysts of middle cranial fossa
      and could be performed as the first surgical choice for these patients.

PMID- 21176650
TI  - [The preliminary study of using neuro-endoscope assisted atlanto occipital
      decompression to treat Chiari type I malformation with syringomyelia].
AB  - OBJECTIVE: To explore and evaluate the methodology of neuro-endoscope assisted
      atlanto occipital decompression in Chiari type I malformation with syringomyelia.
      METHODS: Between January 2007 to January 2008, 8 patients underwent neuro
      endoscope assisted atlanto occipital decompression, including 2 male patients and
      6 female patients (aged 13 to 52 years). During the operations, the surgical
      fields were lightened by the illuminator of endoscope. All the manipulations were
      done outside the sheath of neuroendoscope. The decompression bone window was
      about 2.0 cm * 2.0 cm. After the atlanto occipital fascia was cleared thoroughly,
      dura were opened in 6 cases and intact in 2 cases. RESULTS: There were no
      complications observed in this study. Seven patients were determined as excellent
      in recovery according to the Tator criteria because of apparent improvements in
      superficial sensation. Five of the seven patients had improvements in muscle
      strength. One patient was assessed as good because of stable symptom without
      deterioration. CONCLUSION: Neuro-endoscope assisted atlanto occipital
      decompression is a potential technique worthy of employing in the mini-invasive
      neurosurgical technology.

PMID- 21176651
TI  - [Endoscopic endonasal surgery of trigeminal schwannoma extending into the
      infratemporal fossa].
AB  - OBJECTIVE: To investigate the feasibility of removing extracranial trigeminal
      schwannomas located in the infratemporal fossa by using a purely endoscopic
      endonasal approach. METHODS: From November 2004 to July 2009, 8 patients with
      extracranial trigeminal schwannomas located in the infratemporal fossa (4 male
      patients and 4 female patients, age ranged 31 - 62 years) were surgically treated
      by using a purely endoscopic endonasal approach. RESULTS: The maximum diameters
      of the tumors ranged from 3 to 7 cm. All tumors were completely removed. The
      operation time was 40 to 120 min, blood loss was 300 to 1500 ml. The clinical
      symptoms of some patients were relieved or improved. There were no intraoperative
      and postoperative complications, no deaths in this series. No relapse happened
      during the follow-up. CONCLUSIONS: The purely endoscopic endonasal approach may
      provide a minimally invasive and safe approach to remove extracranial trigeminal
      schwannomas extending into the infratemporal fossa. Radical resection is
      associated with an excellent long-term outcome in this series.

PMID- 21176652
TI  - [Clinical experience of stereotactic biopsy for the brain lesions].
AB  - OBJECTIVES: To investigate the methodology of diversified advanced image-guided
      stereotactic biopsy for the brain lesions, and its diagnostic significance and
      experience in nervous system diseases. METHODS: Retrospectively reviewed 1187
      cases of brain lesions underwent image-guided stereotactic biopsy from December
      1987 to January 2009. There were 694 male (58.5%) and 493 female (41.5%)
      patients, aged from 1 to 85 years (average 39.7 years). There were 607 cases in
      CT-guided, including positron emission computed tomography (PET) guided
      stereotactic biopsy; 580 cases in MRI-guided, including proton magnetic resonance
      spectroscopy ((1)H-MRS) guided stereotactic biopsy. Routine frame was used in 726
      cases and frameless stereotactic biopsy in 461 cases, including neuroendoscopic
      biopsy in 28 cases, guided by computer assisted surgery (CAS) computer-assistant
      robot. In the early 450 cases, CT/MRI images films were employed to measure the
      coordinates of the target by hand, while in the late 737 cases, computer
      assistant planning software rebuilt the CT/MRI images and figured out the optimal
      neurosurgical path for biopsy. RESULTS: The positive diagnosis rate of biopsy was
      97.4%, 983 (82.8%) cases were diagnosed pathologically as brain tumors, and 173
      (14.6%) cases as non-tumor diseases. The tumors mainly including neuroglioma,
      metastatic tumor, primary central nervous system lymphoma and germ cell tumors.
      In non-tumor diseases, mainly including multiple sclerosis, tumefactive
      demyelinating lesion, neurodegenerative disease, inflammation and parasite. The
      biopsy operation caused small hematoma without neurological deficits in 20 cases
      (1.7%), and caused large hematoma (> 10 ml) which need neurosurgical treatment
      (catheterization or craniotomy evacuation of hematoma) in 9 cases (0.8%).
      Hemorrhage associated with biopsy caused 3 cases (0.3%) death. There were no
      severe intracranial infection cases. CONCLUSIONS: The stereotactic biopsy with
      advanced image-guided technique represents a safe, reliable and minimally
      invasive method for pathological diagnosis of intracranial lesions. Moreover, the
      developments of biochemical imaging gives a new concept to the stereotactic
      biopsy.

PMID- 21176653
TI  - [Endovascular treatment of micro-intracranial aneurysms: adverse factors of micro
      catheterization and its relevant managements].
AB  - OBJECTIVES: To investigate adverse factors that may hinder successful placement
      and stabilization of the microcatheter during endovascular therapy of micro
      intracranial aneurysms (<= 3 mm in maximum diameter), and to explore the relevant
      managements. METHODS: Forty-six patients with fifty-one micro-intracranial
      aneurysms treated by endovascular therapy from June 2001 to October 2009 were
      retrospectively analyzed for their intervention data. RESULTS: Adverse factors of
      optimal micro-catheterization mainly included, tortuosity of the proximal vessels
      (PVs) and the parent artery (PA), relative large gap in diameter among the PVs,
      the PA and the microcatheter, relative large divergence in direction among the
      PVs, the PA and the aneurysm dome, and stent deployed in the PA. CONCLUSIONS:
      Carefully considering the direction of the PVs and the PA, the aneurysm's
      location and dome orientation, choosing the microcatheter and microwire after
      balancing among their physical properties, as well as utilizing balloon and/or
      stent assistance, can facilitate micro-catheterization during endovascular
      treatment of micro-intracranial aneurysms.

PMID- 21176654
TI  - [Clinical study on endovascular treatment for symptomatic atherosclerotic
      stenosis of basilar artery].
AB  - OBJECTIVE: To study the feasibility, safety and validity of percutaneous
      angioplasty and stenting (PTAS) for symptomatic atherosclerotic stenosis of
      basilar artery. METHODS: The results of treatment and follow-up of 40 cases with
      symptomatic atherosclerotic stenosis of basilar artery performed PTAS from August
      2003 to December 2009 were studied retrospectively, who had either recurrent
      transient ischemic attacks (TIAs) or obvious ischemic symptoms and resistant to
      medical therapy. RESULTS: PTAS were successfully performed in all the 40 cases
      and the post-operative average residual stenosis descended to 14% +/- 11% from
      pre-operative 82% +/- 14%. After operation the patients were administrated with
      antiplatelet drugs. After procedure the clinic symptoms and signs of ischemia
      were improved obviously in 38 cases and deteriorated in 2 cases whose CT scanning
      showed that the range of infarction in brain stem enlarged. The symptoms improved
      after treatment but 2 patients had neurological deficit. No hemorrhagic
      complications occurred in the group. During the follow-up for 2 months to 7
      years, transcranial doppler ultrasonography in 26 cases demonstrated the blood
      flow was faster than normal in 2 cases, and digital subtraction angiography (DSA)
      in 6 cases showed restenosis in-stent in 1 case. The second stent was implanted
      because of the symptomatic restenosis. In another case the follow-up DSA showed
      occlusion of basilar artery in-stent but there was no ischemia of post
      circulation because the generation of anastomoses. CONCLUSIONS: PTAS is a
      feasible, safe and effective therapeutic method for the patients with symptomatic
      atherosclerotic stenosis of basilar artery. Further study in large number of
      patients is needed for long-term outcome.

PMID- 21176655
TI  - [Value of protective stoma in intersphincteric resection for ultra-low rectal
      cancer].
AB  - OBJECTIVE: To investigate the value of protective stoma in intersphincteric
      resection (ISR) for ultra-low rectal cancer. METHODS: Clinical data of 56 ultra
      low rectal cancer patients without involvement of external anal sphincter treated
      during January 1999 to July 2009 with trans-anal ISR plus trans-abdominal total
      mesorectum excision and coloanal anastomosis were retrospectively analyzed. The
      patients were divided into two groups based on whether they received protective
      ostomy: ostomy group (16 cases) and ostomy-free group (40 cases). The
      postoperative complications as well as anal functional restoration were compared
      between the two groups. RESULTS: Sixteen cases (32.1%) of the 56 patients
      received protective stoma. The complication rate of anastomosis and anus
      complication rate in the ostomy-free group were significantly higher than those
      in ostomy group [35.0% (14/40) and 40.0% (16/40) vs. 1/16 and 1/16; P < 0.05]. In
      the ostomy-free group, one patient developed anastomotic dehiscence and tumor
      recurrence, the patients was given permanent colostomy, and the other three
      patients with lesions in the anastomosis and anus received ostomy and secondary
      surgical treatment, with a reoperation rate of 10.0% (4/40). The anal function of
      patients in the two groups were both decreased after the operation. The rate of
      patients got Kirwan grade I anal sphincter function in the 3rd, 6th and 12th
      month after protective stoma operation was 11/16, 13/15 and 11/13 in the ostomy
      group, respectively; and those were 30.0%, 37.5% and 45.0% in the ostomy-free
      group, respectively. Anal function was significantly better in the ostomy group
      than that in the ostomy-free group during the same postoperative period (P <
      0.05). CONCLUSION: Protective stoma can avoid anastomotic leakage following ISR
      for ultra-low rectal cancer, and alleviate the suffering of anal incontinence in
      the early postoperative period, and is conducive to the restoration of anal
      function.

PMID- 21176656
TI  - [Clinical effect of lower tidal volume combine with lung recruitment maneuver on
      ARDS for post operative esophageal carcinoma surgery patients].
AB  - OBJECTIVE: To study clinical effectiveness and possible side effects of lower
      tidal volume combine with lung recruitment on acute respiratory distress syndrome
      (ARDS) for post operative esophageal carcinoma surgery patients. METHODS: Twenty
      six hypoxemie post operative esophageal carcinoma surgery patients from Cancer
      Hospital and Peking Union Medical College Hospital were included from 1st January
      2007 to 30th September 2009. There were 20 male and 6 female with an average age
      of 65.5 years (51 - 76 years). Circulation was stable among them. They could not
      weaned from mechanical ventilation due to ARDS. Bedside monitoring included
      noninvasive continuous artery blood pressure (NBP), pulse oximetry saturation
      (SPO2). Patients were ventilated on volume control mode. Tidal volumes set to 6
      ml/kg. Recruitment maneuvers were conducted by stepwise rising of positive end
      expiratory pressure (PEEP) level. PEEP, fraction of inspired oxygen (FiO2),
      static compliance of lung (CLS) and arterial blood gas analysis (ABG) before and
      at 30 min after each of twice applying recruitment maneuvers were measured.
      RESULTS: Fifty-two recruitments were completed on these 26 cases. PaO2/FiO2
      improved significantly in 26 cases. The level of FiO2 were significantly lowered,
      CLS were increased significantly 30 min after each of twice applying recruitment
      maneuvers in all 26 cases. No complication was encountered. All patients were
      discharged successfully. CONCLUSION: Hypoxemia of ARDS following esophageal
      carcinoma surgery can be improved by lower tidal volume combine with lung
      recruitment maneuver.

PMID- 21176657
TI  - [Experimental study on the option of antispasmodic drugs for radial artery in
      elderly patients with coronary atherosclerotic heart disease].
AB  - OBJECTIVE: To compare the relief effect of diltiazem, papaverine and
      nitroglycerin on radial artery spasm in elderly patients with coronary
      atherosclerotic heart disease. METHODS: Sixty patients aged beyond 70 years
      underwent coronary artery bypass grafting (CABG) with autologous radial artery
      from July 2009 to March 2010. Redundant radial artery was collected and the
      relief function of different drugs was evaluated through "organ bath" technique
      in vitro. All the patients were randomly divided into 3 groups based on different
      antispasmodic drugs: diltiazem, papaverine and nitroglycerin. Thirty seconds free
      blood flow of radial artery and hemodynamic parameters (heart rate, mean arterial
      pressure and central venous pressure) were assessed before and after intra-radial
      administration of diltiazem, papaverine and nitroglycerin in vivo. RESULTS: All
      three drugs could relieve radial artery spasm in different levels and the
      eventual relief rate was over 80%. Only nitroglycerin could relax radial artery
      completely, the relief capacity of nitroglycerin, diltiazem and papaverine
      decreased in order. There was no significant difference in the hemodynamic
      parameters before and after the injection. Blood flow of radial artery increased
      in nitroglycerin group [(42 +/- 10) ml/30 s vs. (28 +/- 7) ml/30 s, P < 0.05]
      while there was no significant difference in diltiazem [(23 +/- 10) ml/30 s vs.
      (25 +/- 8) ml/30 s, P > 0.05] and papaverine group [(25 +/- 10) ml/30 s vs. (24
      +/- 9), P > 0.05]. CONCLUSIONS: Nitroglycerin could relieve vasospasm of radial
      artery effectively and increased blood flow. Nitroglycerin is the suitable
      antispasmodic drug for radial artery in the elderly patients with coronary
      atherosclerotic heart disease compare with diltiazem and papaverine.

PMID- 21176658
TI  - [Arthroscopic treatment of bursal-side partial-thickness rotator cuff tears].
AB  - OBJECTIVE: To study the surgical techniques and results of arthroscopic treatment
      of bursal-side partial-thickness rotator cuff tears. METHODS: From June 2002 to
      December 2007, 57 patients with bursal-side partial-thickness rotator cuff tears
      underwent arthroscopic treatment. There were 34 male and 15 female patients, the
      average age was 49.7 years (25 - 71 years). Fifteen left shoulder and 34 right
      ones were involved. Seven cases were classified as degree I, 6 as II and 36 as
      III according to Ellman classification. The anterior-posterior and the
      supraspinatus outlet projection of the X-rays were obtained before surgery.
      Twenty-nine patients had been received by sonography and 36 patients had
      undergone MRI examinations. All the patients underwent subacromial bursectomy and
      acromioplasty, 13 cases underwent cuff debridement, 36 cases underwent cuff
      repair. Among them, 3 cases were treated by side to side suture of rotator cuff,
      26 cases were treated by suture anchor, 7 cases were treated by side to side
      suture combined with suture anchor. UCLA scoring system was adopted before
      operation and at the final evaluation. RESULTS: Forty-nine patients had been
      reviewed at least 2 years after the operation with an average of 48 months (2 to
      7 years). The average score was 32.1 +/- 3.8 postoperatively, and the mean pain
      score was 2.9 +/- 1.0 vs 8.4 +/- 1.7 (P = 0.000) for pre- vs. post-operation, the
      function score was 5.4 +/- 1.2 vs. 9.1 +/- 1.4 (P = 0.000), the mean forward
      flexion score was 4.3 +/- 1.1 vs. 4.9 +/- 0.2 (P = 0.000), the mean forward
      flexion strength was 4.0 +/- 0.4 vs. 4.8 +/- 0.4 (P = 0.000), the results were 16
      excellent, 31 good and 2 bad. Forty-seven patients were satisfied with the
      operation. CONCLUSIONS: Arthroscopy is an effective method for the treatment of
      bursal-side partial-thickness rotator cuff tears. The key to the operation lies
      in bleeding control, proper acromioplasty and correct suturing method. This
      surgery has many advantages such as mini-invasion and rapid recovery.

PMID- 21176659
TI  - [The analysis of intracranial aneurysms undergoing surgical treatment].
AB  - OBJECTIVE: To study the surgical principles and treatment options of intracranial
      aneurysms. METHODS: One hundred and thirty nine patients with intracranial
      aneurysms were retrospectively studied, including 80 open-surgery cases and 59
      endovascular-treated cases from January to December in 2009. Open surgical
      methods included clipping, trapping or wrapping and interventional methods
      included simple coiling or stent-assisted coiling. Intra-operative
      electroencephalogram and somatosensory evoked potentials monitoring were
      regularly used. Microvascular doppler ultrasonography and indocyanine green
      videoangiography were used to assess blood flow in parent and branch vessels.
      RESULTS: Seventy-three aneurysms were directly clipped, 6 were trapped and 1 was
      wrapped. Thirty-three aneurysms were coiled and 26 were coiled assisted with
      stents. At discharge, 71 of the 80(88.8%) surgical treated patients had Glasgow
      Outcome Scale score of 4 or 5 points, 3 points in 6 patients (7.5%), 2 points in
      1 patient (1.2%), and 1 point in 2 patients (2.5%). Fifty-four out of 59 cases
      underwent endovascular treatment scored 4 or 5 points (91.5%) and 3 points in 5
      patients (8.5%). CONCLUSIONS: Surgical clipping and endovascular coiling are two
      major treatment choices for intracranial aneurysms. The treatment option should
      be individualized based on the patients' specific conditions, which could have a
      safe, effective and durable outcome.

PMID- 21176661
TI  - [Application of fast track surgery in the perioperative management of primary
      hepatic carcinoma].

PMID- 21176660
TI  - [External validation of the Partin tables 2007 in Chinese prostate cancer
      patients].
AB  - OBJECTIVE: To validate the 2007 Partin tables externally, which are based on the
      population of United States, using a cohort of Chinese prostate cancer patients.
      METHODS: All of the patients enrolled and underwent radical prostatectomy between
      January 2006 and February 2010 were reviewed. The cases without preoperative
      hormone therapy and pelvic lymph node involvement according to radiologic tests
      were used for the external validation of the 2007 Partin tables. A comparative
      analysis of the clinical and pathological parameters of this Chinese cohort and
      Partin tables cohort was performed. Values of areas under the receiver operating
      characteristic (ROC) curve were used to assess predictive accuracy for the
      Chinese cohort. RESULTS: The mean age of the whole cohort was 67 years. The serum
      prostate specific antigen level, Gleason score and clinical stage of this cohort
      were higher than the Partin tables cohort. The pathological outcomes analysis
      revealed that the rates of organ confined disease, capsular penetration, seminal
      vesicle involvement and lymph node involvement were 62.3%, 16.7%, 12.3% and 8.8%,
      respectively. The area under the ROC curve (AUC) for organ confined disease,
      capsular penetration, seminal vesicle involvement and lymph node involvement were
      0.735, 0.653, 0.601 and 0.845. CONCLUSIONS: The Partin tables discriminate well
      for Chinese patients at risk for positive lymph node. The discrimination of organ
      confined disease is also acceptable and the discrimination of capsular
      penetration and seminal vesicle involvement is more limited.

PMID- 21176662
TI  - [The prevention and treatment of liver failure after partial hepatic resection
      for primary hepatic carcinoma].

PMID- 21176663
TI  - [Strategies to reduce surgical risk of hepatectomy in patients with primary liver
      cancer].

PMID- 21176664
TI  - [Improvement of the methods of liver function assessment for primary
      hepatocellular carcinoma].

PMID- 21176665
TI  - [A scoring system to predict ascites after hepatectomy for hepatocellular
      carcinoma].
AB  - OBJECTIVE: To establish a scoring system predicting the ascites postoperatively
      by analyzing the variant factors associated with massive ascites after
      hepatectomy in the patients with hepatocellular carcinoma (HCC). METHODS: From
      January 2005 to January 2010, 324 patients with HCC underwent hepatectomy were
      analyzed retrospectively. There were 282 male and 42 female, aging from 17 to 84
      years (mean age, 54 years). They were divided into two groups according to the
      volume of ascites. Variant preoperative, intraoperative and postoperative factors
      were compared and a scoring system was established to predict the postoperative
      ascites. RESULTS: The univariate analyses revealed that various preoperative
      factors including prothrombin time, activated partial thromboplastin time,
      platelet count, albumin, aspartate aminotransferase had significantly difference
      in the two groups (P < 0.05). The operation time, intraoperative bleeding,
      hemihepatectomy or extended hemi-hepatectomy and the request of blood and serum
      transfusion had significantly difference in the two groups (P < 0.05). The
      multivariate analysis showed that the PLT, AST and the intraoperative plasma
      transfusion, hemihepatectomy or extended hemi-hepatectomy, the urine output and
      the drainage in the first postoperative day were independent factors (P < 0.05)
      for ascites. A scoring system was established based on the analysis. The
      specificity and the sensitivity were 86.2% and 83.3% respectively. CONCLUSION:
      Variant factors are associated with postoperative ascites for hepatocellular
      carcinoma and the scoring system established can predict the ascites after
      hepatectomy accurately.

PMID- 21176666
TI  - [Peri-operative treatment for hepatocellular carcinoma patients complied with
      cirrhosis and hypersplenism].
AB  - OBJECTIVE: To investigate the influence of combined hepatectomy with splenectomy
      on safety of operation for hepatocellular carcinoma patients complied with
      cirrhosis and hypersplenism and the best peri-operative treatment of these
      patients. METHODS: Clinical data of 177 hepatocellular carcinoma patients
      complied with cirrhosis and hypersplenism admitted from January 1999 to December
      2009 were analyzed retrospectively. Among which, 71 patients received concomitant
      splenectomy with hepatectomy (splenectomy group), 106 patients only receive a
      hepatectomy (non-splenectomy group). The safety of operation, complications,
      liver function and WBC and PLT counts were compared between the two groups.
      RESULTS: There was no significant difference of general conditions, counts of WBC
      and PLT between the two groups before operation. The counts of PLT at 1, 10, 30
      day after operation were (88.4 +/- 23.6) * 109/L, (345.3 +/- 98.2) * 109/L and
      (210.8 +/- 92.2) * 109/L respectively in splenectomy group, which were
      significantly higher than that of non-splenectomy group (P < 0.05). The operation
      time of splenectomy group was (216 +/- 105) min, which was longer than that of
      non splenectomy group (P < 0.05), but the blood loss and transfusion rate had not
      significantly difference between the two groups. The complication rates of
      splenectomy group and non-splenectomy group were 11.3% and 6.6% respectively,
      there was no significant difference between the two groups. CONCLUSION: Combined
      hepatectomy with splenectomy will be safe for hepatocellular carcinoma patients
      complied with cirrhosis and hypersplenism as if the operative indication and
      increase the ability of peri-operative treatment are strictly obeyed.

PMID- 21176667
TI  - [Risk factors of early recurrence in patients with gastric cancer after curative
      resection].
AB  - OBJECTIVE: To analyze the clinical and pathologic influencing factors of early
      recurrence in patents with gastric cancer after radical gastrectomy. METHODS:
      Clinicopathological data of 141 patients with recurrence after curative
      gastrectomy for gastric cancer from January 2001 to December 2004 were analyzed
      retrospectively. Risk factors correlated with tumor early recurrence and survival
      difference between early recurrence group (< 1 year, 82 cases) and control group
      (1 year after, 59 cases) were assessed. RESULTS: The 1- and 3-year survival rates
      of in early recurrence group and control group were 36.6%, 2.4% and 100%, 45.8%,
      respectively (P < 0.05). The median survival time after recurrence in the two
      groups was 3, 5 months, respectively (P < 0.05). Univariate analysis showed that
      the age, tumor Borrmann type, tumor site, invasive depth, lymph node metastasis,
      pTNM stage, metastatic lymph node ratio, surgical procedure and intraperitoneal
      hyperthermic perfusion chemotherapy (IHPC) were significant factors associated
      with early recurrence after curative gastrectomy for gastric cancer (P < 0.05).
      Lymph node metastasis, metastatic lymph node ratio and IHPC were independent
      factors associate with early recurrence after curative gastrectomy on
      multivariate analysis (P < 0.05). CONCLUSIONS: The patients with early recurrence
      after the radical gastrectomy have a poorer survival compared with cases recur
      later. Lymph node metastasis, metastatic lymph node ratio and IHPC are
      independent factors associate with early recurrence after curative gastrectomy
      for gastric cancer.

PMID- 21176668
TI  - [The clinical features and surgical treatment strategies of cervical kyphosis].
AB  - OBJECTIVE: To analyze the clinical characteristics and the surgical treatment
      strategy of cervical kyphosis. METHODS: From March 2006 to October 2009, 31 cases
      of cervical kyphosis were treated. According to the clinical features and imaging
      findings, different treatment methods were used. There were 9 patients in
      operation group, including 4 male and 5 female patients, aged from 17 to 72 years
      (average age of 35 years). Among them, 5 cases were idiopathic kyphosis and 4
      cases were caused by laminectomy or other reasons. There were 22 patients in
      conservative treatment group, including 11 male and 11 female patients, aged from
      14 to 40 years (average age of 29 years), who were all idiopathic cervical
      kyphosis. Before and 1 week after operation, clinical assessment were taken for
      the patients in operation group using Spinal Cord Injuries Classification
      Standard of American Spinal Injury Association (AISA). During the periodic
      review, the anteroposterior, normal sagittal films of cervical spine were taken.
      At 1 week and every 6 months after operation, MRI films were also taken. These
      films were studied to evaluate the effects of the operations. In the conservative
      group, assessment of treatment results by studying anteroposterior and normal
      lateral views of cervical spine were were taken every month. The clinical
      characteristics and the surgical treatment strategies of these patients were
      analyzed. RESULTS: In operation group, 9 cases were followed up for 6 to 18
      months, all patients did not failed in internal fixation and fusion. AISA
      neurological score and neurological function significantly improved. Three days
      after operation the average Cobb angle was -1.29  degrees  (preoperative 54.24 
      degrees ). In conservative group, the average Cobb angle was -5.41  degrees 
      (before treatment 11.20  degrees ) 4 months after the treatment. The symptoms of
      neck shoulder and back pain disappeared, and all patients were followed up for 3
      to 24 months, with no recurrence of symptoms. CONCLUSIONS: In the early period of
      cervical kyphosis, adopt postural therapy, plaster braces to correct an imbalance
      in cervical spine biomechanics can prevent deformity development. According to
      patients' clinical characteristics, choosing individual treatment programs can
      correct the severe cervical kyphosis and achieve good outcome.

PMID- 21176669
TI  - [The survival and functional outcome of primary bone sarcomas in distal lower
      extremity].
AB  - OBJECTIVE: To analyze the oncological and functional outcome of limb salvage in
      this location. METHODS: From November 2003 to January 2010, 20 patients with
      primary malignant bone tumors of the distal lower extremity were treated. There
      were 15 male and 5 female, the mean age was 20 years. Among 14 patients with
      malignant distal tibial sarcoma, 11 patients had ankle arthrodesis reconstructed
      by using allograft (7 patients) or autografts (4 patients), the other 3 patients
      underwent below-knee amputation. Three patients with osteosarcoma of distal
      fibula reconstructed with ipsilateral fibular head, 3 patients with calcaneus
      osteosarcoma underwent total calcanectomy and reconstructed with fibular segment
      and iliac crest. The mean follow-up was 36.4 months. RESULTS: Five of 7 (71.4%)
      patients with allograft reconstruction were associated with delayed wound
      healing, however, only 1 of 10 patients with autograft had this problem (P =
      0.036). One local recurrence was observed, 2 osteosarcoma patients died of
      disseminated disease. The estimated 2-year and 5-year overall survival for the
      patients with malignant tibial sarcomas were 92.9% and 79.6% respectively, for
      the patients with distal tibial high-grade osteosarcoma were 87.5% and 70.0%
      respectively. The mean functional MSTS score was 82% for limb salvage patients.
      CONCLUSIONS: The survival of patients with primary malignant bone tumor of distal
      lower extremity seems to be better than that of other sites. Limb salvage can
      provide satisfactory local control and functional results.

PMID- 21176670
TI  - [Influence of the insert design on clinical results and kinematics of the knee
      after total knee arthroplasty].
AB  - OBJECTIVE: To investigate the influence of the insert design of knee prosthesis
      on clinical results and kinematics of the knee after total knee arthroplasty
      (TKA). METHODS: Forty-two knees in 28 patients with knee osteoarthritis
      undergoing TKA using the GENESIS II from July 2007 to June 2009 were included in
      this study, mean follow-up of 27.7 months. The cases were divided into 2 groups
      according to the type of insert, one was high flexion insert group (23 knees) and
      the other was standard insert group (19 knees). Two groups were compared by
      clinical ratings of knee function. The motion of flexion and extension of the two
      groups was observed by cyclic fluoroscopy and the data was analyzed by mapping
      software. The influence of the insert design of knee prosthesis on kinematics of
      the knee after TKA was investigated by comparing the parameters of the two groups
      during the movement of knee joint, including femoral roll back and extensor
      mechanism arm. RESULTS: The range of motion of standard insert group and high
      flexion insert group was 120 degrees  and 123 degrees  respectively with no
      difference between them. There was no difference of knee society clinical rating
      system in both groups. Feller score of high flexion insert group was higher than
      the standard insert group, the difference was significant statistically (P =
      0.012). In the imaging measurement, the two groups had no differences in femoral
      rollback and extensor mechanism arm during the 0 to 120 degrees  range of
      movement. The two groups appeared significant statistically (P = 0.034) in the
      extensor mechanism arm when flexion extended to 130 degrees . CONCLUSIONS: The
      high flexion improved design may play a certain role on reducing anterior knee
      pain and improving knee function after TKA. However, the improved design may be
      reduced the extensor mechanism arm when high flexion, so that affecting the work
      ability of quadriceps.

PMID- 21176671
TI  - [Video-assisted minimally invasive radiofrequency ablation in the treatment of
      persistent atrial fibrillation].
AB  - OBJECTIVE: To evaluate the effectiveness of the video-assisted minimally invasive
      radiofrequency ablation combined irbesartan use for the treatment of the
      persistent atrial fibrillation (AF). METHODS: From January 2006 to December 2009,
      83 patients with persistent AF having a video-assisted minimally invasive
      radiofrequency ablation. There were 58 males, 25 females with a mean age of (57
      +/- 11) years. Mean duration of preoperative AF was (61 +/- 65) months. Follow-up
      for the whole patients ranged from 1.0 to 3.6 years [mean (2.2 +/- 0.8) years].
      Patients were randomly divided into irbesartan group (n = 42) and without
      irbesartan group (n = 41) postoperatively. RESULTS: No patient died
      postoperatively. During follow-up, there was 1 patient died of unknown reason. At
      the end of the procedure, 38 patients (45.7%) were sinus rhythm, 4 patients
      (4.9%) were pacing rhythm, 5 patients (6.0%) were atrial flutter or atrial
      tachycardia, and 36 patients (43.4%) were AF. Before discharge, 53 patients
      (63.9%) were sinus rhythm, 24 patients (28.9%) were AF. At late follow-up, 65
      patients (80.2%) were sinus rhythm; 14 patients (17.3%) were AF or atrial
      flutter. After follow-up, the Kaplan-Meier analysis showed the irbesartan group
      had fewer patients with AF (P = 0.020). The hazard ratio for AF recurrence in
      patients treated with irbesartan was 0.24 (95% CI: 0.087 to 0.637, P = 0.004).
      CONCLUSIONS: The video-assisted minimally invasive radiofrequency ablation is
      safe and effective. The patients treated with irbesartan have a lower rate of
      recurrence of AF.

PMID- 21176672
TI  - [Study on micrometastases in pelvic lymph nodes detected by real-time reverse
      transcriptase polymerase chain reaction with clinically localized prostate cancer
      before radical prostatectomy].
AB  - OBJECTIVE: To clarify the significance of micrometastases in pelvic lymph nodes
      in patients with neoadjuvant hormonal therapy (NHT) before radical prostatectomy
      (RP). METHODS: Twenty-one patients with clinically localized prostate cancer who
      received NHT between August 2007 and March 2010 were observed. The patients were
      clarified into four groups: pathological examination was positive (group A), real
      time PCR examination targeting prostate specific antigen (PSA) mRNA and prostate
      specific membrane antigen (PSMA) mRNA were positive (group B), pathological
      examination and real-time PCR examination targeting PSA mRNA and PSMA mRNA were
      both negative (group C), and the control group (group D). After a standard
      bipedal lymphangiography the films were reviewed carefully by an experienced
      radiologist. If positive lymph nodes were seen or suspected, a thin-walled 22
      gauge needle were directed transabdominally under fluoroscopic control into the
      area of question and an aspirate was obtained. The expression of PSA and PSMA in
      aspirate were assessed by a fully quantitative real-time PCR. The specimens were
      regarded in which either PSA mRNA or PSMA mRNA were positive as showing the
      "presence of micrometastasis". Lymph node specimens were also stained
      immunohistochemically with an antibody PSA after RP. RESULTS: Pathological
      examination detected lymph node metastases from 3 cases, and real-time PCR
      further identified lymph node micrometastases from 14 cases with no pathological
      evidence of nodal involvement. The expression level of PSA mRNA and PSMA mRNA
      were statistically significant in patients with histological confirmed lymph node
      metastases and micrometastases detected by real-time PCR despite the lack of
      histological evidence, and the expression level of PSA mRNA and PSMA mRNA in
      aspirate were higher than the lymph node between the group A and group B.
      CONCLUSIONS: Although residual foci of atrophic prostate cancer cells in resected
      lymph nodes after NHT can be difficult to diagnose by pathological examination,
      the present results show the usefulness of quantitative real-time PCR targeting
      PSA and PSMA mRNA for detected micrometastatic tumour foci in pelvic lymph nodes
      from fine needle aspiration biopsy of lymph nodes before RP.

PMID- 21176673
TI  - [Influence of nuclear factor erythroid 2-related factor 2 genotype on tumor
      necrosis factor-alpha and metalloproteinase-9 expression in spinal cord after
      spinal cord injury in mice].
AB  - OBJECTIVE: To investigate the role of nuclear factor erythroid 2-related factor 2
      (Nrf2) as a key transcription factor of cytoprotection against inflammation in
      the spinal cord upregulation of matrix metalloproteinase-9 (MMP-9), tumor
      necrosis factor-alpha(TNF-alpha) after spinal cord injury (SCI). METHODS: Wild
      type Nrf2(+/+) and Nrf2(-/-)-deficient mice were subjected to a murine SCI model
      induced by the application of vascular clips (force of 10 g) to the dura after a
      three-level T8-T10 laminectomy. The wet/dry weight ratio was used to reflect the
      percentage of water content of impaired spinal cord tissue at 48 h after SCI. The
      mRNA levels of MMP-9 were determined using reverse-transcriptase polymerase chain
      reaction (RT-PCR), and the protein levels of TNF-alpha and MMP-9 were detected by
      enzyme-linked immunosorbent assay at 24 h after SCI. Furthermore, gelatin
      zymography analysis was used to show MMP-9 activity of spinal cord tissue at 24 h
      after SCI. Software SPSS 16.0 was used for the statistical analysis. RESULTS:
      After SCI, spinal cord water content, the expression of TNF-alpha and MMP-9 all
      increased in both injured Nrf2(+/+) and Nrf2(-/-) mice compared with their
      respective sham-operated mice. However, Nrf2(-/-) mice were shown to have more
      severe spinal cord edema, more TNF-alpha expression, more production and activity
      of MMP-9 compared with their wild-type Nrf2(+/+) counterparts after SCI (P <
      0.05). CONCLUSIONS: The results suggest that Nrf2 plays an important protective
      role in limiting the spinal cord upregulation of TNF-alpha and MMP-9 after SCI.
      It may be a new therapeutic target of SCI.

PMID- 21176674
TI  - [Lentiviral vector-mediated RNA interfere gene Nogo receptor to repair spinal
      cord injury].
AB  - OBJECTIVE: To evaluate the effects of lentiviral vector-mediated RNA interfere
      gene Nogo receptor (NgR) of rat cortical neurons in repairing spinal cord injury.
      METHODS: The recombinant-lentiviral vector with small inferring RNA siNgR199
      which had been constructed was transfected into rat cortical neuron cells in
      vitro in 3 multiplicity of infection (MOI). The infection rate was determined
      with fluorescent microscope, and the target gene was detected by PCR analysis.
      Then, the recombinant was injected into the cortical motor area of the rats with
      severe spinal cord injury, and the saline was also injected into other rats with
      severe spinal cord injury as a match control. The functional recovery of the
      rats' hindlimb was assessed using BBB score and the nerve fiber of the injured
      region was observed by nerve tracing. RESULTS: The rate of recombinant infecting
      rat cortical neuron in vitro exceeded 99%. PCR analysis confirmed that the effect
      of lentiviral vector-mediated RNA interfering gene NgR of rat cortical neurons in
      vitro was 61%. Although all rats with spinal cord injury were observed to have
      the hindlimb functional recovery, these rats injected with recombinant had better
      hindlimb functional recovery than others showing by more BBB score (P < 0.01).
      Moreover, it was found that some nerve fiber passed the injured spinal cord
      region of the rats which were injected with recombinant. CONCLUSION: The
      recombinant lentiviral vector with siNgR199 which had been constructed is able to
      promote the growth of nerve fiber and the functional recovery of the rats'
      hindlimb.

PMID- 21176675
TI  - [The anatomic study of transferring thoracic nerve roots to lumbar nerve root
      inside the spinal canal of paraplegia].
AB  - OBJECTIVE: To study the fundamental anatomy of transferring T(9-12) nerve roots
      to L(2-4) nerve root for the quadriceps function recovery inside the spinal canal
      of paraplegia. METHODS: Thoracic and lumbar spinal canal and spinal dura mater of
      5 adult cadavers (male 2 and female 3) were opened and explored. Investigated
      including: the position which T9-L4 nerve root generated from spinal cord; the
      relation between the position which T9-L4 nerve root generated from spinal cord
      and T12 vertebrae and L1 vertebrae; The length beginning part of T9-L4 nerve root
      inside the spinal canal. The diameter of T9-L4 nerve root. The distance between
      the T9-L4 nerve root separately. The distance between the position which T(9-12)
      nerve root separately generated from dura mater and the middle of L2 vertebrae.
      RESULTS: T9 nerve root generated from the middle part of T9 vertebrae; L4 nerve
      root generates from middle part of L2 vertebrae. The average length of T9-L4
      nerve root inside the spinal canal separately was 16.12, 22.97, 30.43, 43.47,
      56.02, 70.03, 88.70 and 113.65 mm. The average diameter of T9-L4 nerve root
      separately was 2.45, 2.04, 1.96, 2.18, 2.32, 2.56, 3.10 and 3.26 mm. The average
      distance between the beginning part of T9-L4 nerve root separately was 22.87,
      25.08, 28.47, 27.38, 29.78, 31.93 and 31.00 mm. The average distance between the
      position which T(9-12) nerve root separately generated from dura mater and the
      middle of L2 vertebrae was 118.69, 95.82, 70.74, and 42.27 mm. CONCLUSIONS: T(9
      12) nerve root can be used as donor nerve for repair L(2-4) nerve root. The level
      of L2 vertebrae can be anastomose site of the recipient nerve.

PMID- 21176676
TI  - [Some new trends of HIV/AIDS epidemic in China].

PMID- 21176677
TI  - [Proportions and correlates of recent HIV infections among newly reported
      HIV/AIDS cases from 2005 through 2009 in Dehong prefecture, Yunnan province].
AB  - OBJECTIVE: To determine the proportions and correlates of recent HIV infections
      among newly reported HIV/AIDS cases from 2005 through 2009 in Dehong prefecture,
      Yunnan province. METHODS: All available serum samples of newly reported HIV/AIDS
      cases during 2005 - 2009 period in Dehong prefecture, were tested using the BED
      HIV incidence capture enzyme immunoassay (BED-CEIA). RESULTS: A total of 9367
      HIV/AIDS cases were newly reported in 2005 through 2009, of whom 7252 (77.4%)
      were tested with BED-CEIA. Among the tested, 954 (13.2%) were positive for BED
      CEIA and were regarded as recent HIV infections. The proportion of recent HIV
      infection among newly reported HIV/AIDS cases was 11.21% in 2005, 11.87% in 2006,
      17.55% in 2007, 13.22% in 2008, and 12.22% in 2009. Multiple logistic regression
      analysis indicated that the proportion of recent HIV infections among newly
      reported HIV/AIDS cases in 2009 was significantly higher among females, those
      aged 11 - 19 years, and internal residents outside of Dehong prefecture, but
      significantly lower among immigrants who were mostly from Myanmar, than local
      residents. CONCLUSION: From 2005 to 2009, the proportion of recent HIV infections
      among newly reported HIV/AIDS cases in Dehong prefecture in Yunnan province was
      fluctuating slightly. Future research is needed to examine its long-term and
      secular trend. Such proportion was significantly different by different
      sociodemographic characteristics.

PMID- 21176678
TI  - [Survival analysis on 3103 HIV/AIDS patients receiving antiretroviral treatment
      in Dehong prefecture, Yunnan province].
AB  - OBJECTIVE: To determine the survival rate of HIV/AIDS patients after receiving
      free antiretroviral treatment in Dehong prefecture, Yunnan province. METHODS: A
      retrospective cohort analysis was conducted on all the HIV/AIDS patients aged
      over 16 years who had started antiretroviral treatment during January 2007
      throughout December 2009 in Dehong prefecture. RESULTS: A total of 3103 HIV/AIDS
      patients had received antiretroviral treatment during the study period. Among
      them, the mean age was (36.0 +/- 9.9) years and 62.4% were males. 66.2% of them
      were infected with HIV through heterosexual transmission, and the mean treatment
      follow-up time was 21.7 months. Most patients well complied with the treatment,
      i.e., the average times of not taking the medicine were less than 5 per month.
      The cumulative survival rate of antiretroviral treatment after 1, 2, 3, 4, and 5
      years were 0.95, 0.94, 0.93, 0.92, and 0.92, respectively. Data from the Cox
      proportional hazard regression model analysis indicated that, after adjustment
      for age, gender, and marital status, the baseline CD4(+)T cell counts and
      transmission route could significantly predicate the rates of survival. Those who
      were with baseline CD4(+)T cell counts as 200 - 350/mm(3)were less likely to die
      of AIDS than those with CD4(+) T cell counts < 200/mm(3) (Hazard Ratio or HR =
      0.16, 95%CI: 0.09 - 0.28), and HIV-infected through mother-to-child transmission
      or routes other than heterosexual transmission were less likely to die of AIDS
      than through injecting drug use (HR = 0.35, 95%CI: 0.13 - 1.00). CONCLUSION: Free
      antiretroviral treatment had significantly improved the survival of HIV/AIDS
      patients. Earlier initiation of antiretroviral treatment was likely to have
      achieved better survival effects.

PMID- 21176679
TI  - [Study on HIV related stigma and discrimination among people living with HIV/AIDS
      and their family members].
AB  - OBJECTIVE: To understand the perceived stigma and discrimination and received
      stigma and discrimination as well as the differences and reasons of them among
      people living with HIV/AIDS and their family members. METHODS: 307 people were
      investigated and 117 of which were HIV/AIDS and the others were their family
      members. Face to face interview was carried out. RESULTS: HIV/AIDS and their
      family were living in the social environment rounded by stigma and
      discrimination. Stigma and discrimination could be divided into perceived stigma
      and discrimination and received stigma and discrimination, and these two kinds of
      stigma and discrimination were statistically significant different between
      HIV/AIDS and their family members (t = -12.540, P = 0.000), and the perceived
      stigma and discrimination was more serious than received stigma and
      discrimination. The perceived stigma and discrimination were related to their
      self-efficacy (OR = 0.558, P = 0.041), family APGAR (OR = 0.650, P = 0.027),
      infected with HIV or not (OR = 2.116, P = 0.004). The received stigma and
      discrimination were related to their self-efficacy (OR = 0.468, P = 0.028),
      family APGAR (OR = 0.427, P = 0.000) whether infected by HIV (OR = 3.412, P =
      0.001). CONCLUSION: Stigma and discrimination did exist in the environment where
      HIV/AIDS and their family lived, suggesting that it was necessary to develop a
      series of policies and measures to fight against stigma and discrimination.

PMID- 21176680
TI  - [Study on the AIDS-related high risk behaviors of men who have sex with men under
      the experience of exchanging money for the same sex].
AB  - OBJECTIVE: To investigate the AIDS-related high risk behaviors of men who have
      sex with men (MSM) who ever exchanged money for the same sex. METHODS: Target
      sampling for cross-sectional study and valid anonymous questionnaires were
      adopted to compare the differences of AIDS-related high risk behaviors between
      MSM with the experience of exchanging money for the same sex and those without
      that experience. 1959 rstadied samples were recruited in nine cities. SPSS 13.0
      was used and t, chi(2) and Mann-Whitney tests were taken for statistical
      analysis. RESULTS: Compared to corresponding ones without "buying" the same sex
      experience, MSM who ever engaged in "buying" sex had the characteristics of being
      prone to in marriage and living in larger cities with older age and higher income
      (P < 0.01). They also had a significant larger number in the following events:
      total sexual partners, anal sex and oral sex episodes with same sex, number of
      sexual partners, anal sex and oral sex in the previous six months, with the
      figure of median 50.0, 20.0, 20.0, 5.0, 4.0, 5.0 respectively. 31.5% had ever
      participated in 'group sex', 48.0% had sex with male partners away from his own
      region in the previous year, 70.5% had sexual intercourse with strangers at MSM
      avenues in the last six months. The OR (95%CI) values were 2.288 (1.702 - 3.077),
      3.231 (2.462 - 4.241), 2.840 (2.140 - 3.770). All the above mentioned figures
      were higher than those without the experience, with significant differences. They
      had a significant lower rate of 45.7% of condom use while having sex with female
      partners (P < 0.05). CONCLUSION: MSM with the experience of exchanging money for
      the same sex would have more AIDS-related high risk behaviors, AIDS preventative
      measures should be taken to target different subgroups.

PMID- 21176681
TI  - [Risk behavioral networks of newly reported HIV infections in Taizhou prefecture,
      Zhejiang province].
AB  - OBJECTIVE: To understand the risk behavioral networks of newly reported HIV
      infections in Taizhou prefecture, Zhejiang province. METHODS: Newly reported HIV
      infections from May 2008 through March 2010 in Taizhou prefecture were invited to
      participate in a cross-sectional survey which requested numbers and contact
      information of individuals with whom they had had high risk contacts as well as
      risk behavioral acts with them. Persons having had risky contacts with HIV
      infected cases were thereof approached to participate in this survey and to
      receive HIV testing. Those who tested positive for HIV were subject to further
      round of the surveys. RESULTS: A total of 267 HIV cases were newly reported
      during this study period. Among them, 191 participated in the survey and served
      as 'index cases', including 158 cases identified from routine HIV surveillance
      programs and 33 cases identified from the present survey. Heterosexual
      transmission was the primary transmission route (74.9%, or 143/191), followed by
      homosexual transmission (19.4%, or 37/191) and injection drug use (5.8%, or
      11/191). These 191 HIV cases reported a total of 1152 individuals with whom they
      had had risky contacts. They were able to provide contact information of 461 risk
      contacts. Of them, 129 received HIV testing and 61 (47.3%) tested positive for
      HIV. HIV prevalence was the highest among spouses or long-term sex partners of
      HIV cases (45.6%, or 47/103) and male sex partners of HIV-infected men having sex
      with men (MSM) (60.0%, or 12/20). Condom use was very low among them, with only
      33.9% consistently using condoms for sex. CONCLUSION: Newly reported HIV
      infections in Taizhou prefecture reported a large and complicated risk behavioral
      networks and low condom use, suggesting a potential risk of HIV among these
      connected people, especially among MSM. Much efforts are needed to intervene
      these high risk subgroups and high risk behavioral networks.

PMID- 21176682
TI  - [Genetic characteristics of HIV-1 CRF01_AE strains circulating in Beijing].
AB  - OBJECTIVE: To analyze the genetic characteristics of HIV-1 CRF01_AE strains
      prevailing in Beijing. METHODS: Plasma samples were collected from the newly
      diagnosed HIV-1 individuals being reported during 2006 to 2008 in Beijing. Gag
      gene fragments were amplified from RNA template which were extracted from plasma
      by RT and nested PCR methods. 105 CRF01_AE sequences were analyzed by
      phylogcnetic methods and characterized through calculating the genetic distance
      and Entropy analysis. RESULTS: There were four main sub-clusters in the
      phylogenetic tree. We named them as sub-clusters Homo-Max (67 sequences), Hetero
      (6 sequences), Mix (8 sequences) and Homo-Min (18 sequences) respectively, based
      on the mode of transmission. It was found that no international reference strain
      was closely related to the sub-cluster Homo-Max, Hetero or Homo-Min, including 91
      samples. The strains in sub-cluster Mix consisting 8 cases that were closely
      related to the strains identified in Thailand and Vietnam. Genetic distance
      analysis on gag genes showed that the diversity of sub-clusters Homo-Max and Homo
      Min was obviously less than that of the sub-cluster Hetero or Mix. When compared
      with sub-cluster Mix, there were 37, 29 and 11 significantly different
      nucleotides polymorphism compositions sites in sub-clusers Homo-Max Homo-Min and
      Hetero. CONCLUSION: This was the first report describing that four main epidemic
      sub-clusters were existed in CRF01_AE strains prevailing in Beijing. The virus
      with sub-cluster Homo-Max was the dominant strain in this region with shorter
      period of circulation and higher proportion seen in the HIV-infected persons. The
      virus in sub-cluster Mix was highly homologic with the CRF01_AE strains from
      Thailand and Vietnam.

PMID- 21176683
TI  - [Impacts of culture in the intervention activities for high risk groups on AIDS].

PMID- 21176684
TI  - [The application of national outbreak automatic detection and response system,
      China].

PMID- 21176685
TI  - [Study on the incidence and risk factors of dementia in elderly residents from
      communities in Beijing].
AB  - OBJECTIVE: To study the incidence of dementia and its risk factors among the
      elderly living in the community of Beijing. METHODS: A sample of 2788 elderly
      residents from Beijing were investigated regarding the incidence of dementia
      which was diagnosed using two-stage method in 1997. In the first stage,
      questionnaire was filled, including MMSE checked up. In the second stage, all the
      elderly who had lower MMSE score and some with normal MMSE score were examined by
      neurologists. The clinical diagnosis of dementia was set up by two neurologists
      according to the criteria of DSM-III-R and NINCDS-ADRDA. The same sample was
      followed up on 2000 and 2004 by the same way, with the overall time for following
      up as 7.25 years. RESULTS: 171 dementias cases were diagnosed among the 2788
      elderly in 1997. At the end of the survey, another 180 new cases developed. The
      average weighted incidence was 0.84/100 person year, adjusted by age (it's same
      followed), with 0.64/100 person year in males and 1.01/100 person years in
      females. The incidence of vascular dementia was 0.35/100 person years, with male
      as 0.39/100 person year and female as 0.32/100 person years. The incidence of
      dementia was increasing with age, but decreasing with time of education by
      Multinomial Logistic Regression Analysis. Old age and illiterate appeared to be
      the risk factors for dementia. People with stroke history and elevated systolic
      blood pressure were risk factors for vascular dementia. CONCLUSION: The incidence
      of dementia in the elderly in Beijing was higher than in other areas of China.
      Old age and illiterate were risk factors for dementia. Being male, illiterate,
      with stroke history and elevated systolic blood pressure were risk factors for
      vascular dementia.

PMID- 21176686
TI  - [Prevalence of microalbuminuria and its related factors among different genders
      in general population of Beijing].
AB  - OBJECTIVE: Microalbuminuria (MAU) is generally defined as an early effective
      index of cardiovascular disease and renal disease. Our study aims to investigate
      the prevalence of MAU and its related factors among people living in Beijing.
      METHODS: In a cross-sectional study, 2080 subjects (810 men and 1270 women) are
      recruited, with age distribution as 50.87 +/- 13.10 years (mean +/- standard
      deviation). Urine albumin-creatinine ratio (ACR) is used to screen for
      microalbuminuria. All the data is analyzed with multivariate logistic regression
      method to explore the related factors for MAU. RESULTS: The overall prevalence of
      MAU in general population of Beijing is 17.50%, with male as 15.43% and female as
      18.82% (P < 0.05). Results from the multivariate logistic regression analysis
      reveal that the independent risk factors of MAU in men are age (OR = 1.02), blood
      pressure (OR = 1.02), serum creatinine (OR = 1.04), while age (OR = 1.04),
      systolic blood pressure (OR = 1.02), serum creatinine (OR = 1.08), body mass
      index (OR = 1.07), total cholesterol (OR = 2.05) in women. The protective factor
      of MAU in women is HDL-C (OR = 0.44). CONCLUSION: Our findings indicate that the
      prevalence of MAU in Beijing area is higher than those in other areas in China or
      abroad. The prevalence in females is higher than that in males (P < 0.05). There
      is a gender difference in the related factors of MAU.

PMID- 21176687
TI  - [Association of ankle-brachial index and pulse wave velocity with stroke in Han,
      Uighur, and Kazakh population of Xinjiang].
AB  - OBJECTIVE: To investigate the relationship between stroke and ankle-brachial
      index (ABI), pulse wave velocity (PWV) in Han, Uighur, and Kazakh populations of
      Xinjiang. METHODS: Data was from the investigation of cardiovascular risk survey
      (CRS) program among different nationalities in Xinjiang from October 2007 to
      March 2010. A total of 14 618 samples aged over 35 with complete data dimension
      were surveyed. RESULTS: (1) There were 633 patients with stroke, including 258
      Hans (4.48%), 247 Uighurs (5.18%), and 128 Kazakhs (3.13%). The incidence of
      stroke was significant different in the three ethnic groups (P < 0.001). (2)
      Compared to the Han population, the incidence of stroke was higher (OR = 1.304)
      in Uighur but lower (OR = 0.794) in Kazakh. (3) PWV was significant different
      between stroke and non-stroke patients. After adjustment for age, body mass
      index, systolic blood pressure, triglyceride, total cholesterol and other risk
      factors, the difference remained significant, indicating that PWV (OR = 1.001, P
      < 0.001) might associate with the occurrence of stroke. CONCLUSION: The results
      of this study showed that the incidence of stroke was significantly different in
      the three ethnic groups. PWV might associate with the occurrence of stroke.

PMID- 21176688
TI  - [Extent and relative changes of equities in using the prenatal care services
      among premature delivery women with different educational levels].
AB  - OBJECTIVE: To understand the extent and relative changes of equities in using the
      prenatal care services among premature delivery women from 4 counties/cities in
      Jiangsu and Zhejiang provinces, from 1995 to 2000. METHODS: The study population
      consisted of 97 537 women who delivered singleton live birth of 28 to 41
      gestational weeks in 4 counties/cities of Jiangsu and Zhejiang provinces, from
      1995 to 2000. The proportions of women with early prenatal visit, of those with
      at least five prenatal visits and the hospital delivery rates between premature
      and term delivery groups were calculated. Inequalities in the above indictors by
      comparing rate difference (RD), rate ratio (RR) and concentration index (CI)
      among women with different educational levels, were examined. Chi-square and One
      way ANOVA were used to compare the differences. RESULTS: The proportions of
      having received early prenatal among those women with premature delivery in
      different education levels were 82.89%, 91.06%, 93.96%, 93.11% respectively,
      which were less than that of those with full term delivery (86.36%, 93.95%,
      95.65%, 96.41%, P = 0.008). The proportions of having received early prenatal
      among the women with high educational levels were higher (RD = -10.05, RR = 0.90,
      CI = 0.0104) than those with low educational attainment (RD = -10.22, RR = 0.89,
      CI = 0.0131); The proportions of having received at least five prenatal visits
      among those women with premature delivery in different education levels were
      86.54%, 93.17%, 92.99%, 96.49%, respectively, which were less than those with
      full term delivery (94.60%, 96.65%, 96.15%, 96.66%, P = 0.005). The proportions
      of having had at least five prenatal visits among the women with high educational
      attainment were higher (RD = -2.06, RR = 0.98, CI = 0.0006) than those with lower
      educational attainment (RD = -9.95, RR = 0.90, CI = 0.0077); The proportions of
      hospital delivery among the women with full term delivery in different education
      levels were significantly higher (99.45%, 99.75%, 99.83%, 99.77%) than those with
      premature deliveries (98.42%, 99.54%, 99.61%, 100.00%, P = 0.005). The
      proportions of hospital delivery among women with high educational attainment was
      higher (RD = -0.32, CI = 0.0003) than those with lower educational attainment (RD
      = -1.58, CI = 0.0013). CONCLUSION: Education related inequities in prenatal care
      utilization had not been improved among the Chinese women under our study.
      Inequities were seen in those women with full-term delivery the preterm delivery
      ones.

PMID- 21176689
TI  - [Self-management behaviors among children after exposure to rabies in two severe
      rabies epidemic areas of China].
AB  - OBJECTIVE: To understand the situation of rabies exposure and self-management
      behaviors among primary school students from rabies epidemic areas in China.
      METHODS: This population-based investigation was conducted in Guizhou and
      Guangdong provinces which had been severe epidemic areas of rabies in China from
      January 2007 to May 2008. Primary schools from two prefectural, two county, four
      township and four village levels were selected in the 2 provinces. Students were
      sampled from each grade of the 12 schools to collect information on post-exposure
      prophylaxis. RESULTS: In the 2408 primary school students interviewed, 290
      person/times exposure were found from 2007 to 2008. The self wound-treatment
      rates was 47.93%, with 16.55% of them went to the clinic for care-seeking
      initiatively and 63.79% informed their parents or teachers. However 23.10% of the
      students did nothing after exposure. Students in Guangdong province had lower
      exposure rate and higher rate of good management behaviors than in Guizhou. No
      significant statistical difference was found between the self-management
      behaviors among male and female students or among different levels of primary
      schools. The proportion of disinfection on wounds with alcohol and seeking
      medical treatment in rabies clinic initiatively were both low in all grades of
      the students but the proportion of telling their parents or teachers about the
      exposure among children was high in all grades of students. CONCLUSION: Some
      students after rabies exposure did not have any disposal in Guangdong and Guizhou
      provinces. Related education should be strengthened.

PMID- 21176690
TI  - [An investigation on self-harm episodes and their relationship with suicidal
      psychology and behaviors in 2713 college students].
AB  - OBJECTIVE: To investigate the episodes and influencing factors on self-harm and
      to explore the relationship between self-harm episodes and suicidal psychology
      and behaviors in college students. METHODS: Four universities were selected using
      cluster sampling method in Anqing city and Chaohu city. Totally, 2713 college
      students completed this survey. Data were analyzed by Pearson Chi-square and
      logistic regression. RESULTS: In the last six months, rates of highly lethal self
      harm, less lethal self-harm with visible tissue damage, self-injury without
      visible tissue damage, self-harmful behaviors with latency damage, other self
      harmful behaviors with menticide were 1.9%, 5.5%, 15.3%, 21.2% and 17.0%
      respectively. The total rate of self-harm was 31.3%. 73.1% of the students with
      self harmful experiences had the above mentioned behaviors more than 3 times in
      the last six months. The top 3 reasons for taking self-harm actions were: having
      learning problems (43.1%), failed love affairs (25.0%) and having conflicts with
      others (23.9%). There were different influencing factors among different kinds of
      self-harm episodes. Depression was the risk factor of self-harm. The higher score
      of having high self-esteem was the protective factor of all kinds of self-harm
      actions except highly lethal ones. Higher score of difficulties in identifying
      feelings was one of the risk factors. The rates of suicidal psychology and
      behaviors in students with self-harm were significantly higher than those in
      students without those behaviors. Result from linear chi(2) test indicated that
      the graveness of tissue damage of self-harm was higher along with the rates of
      suicidal psychology and behaviors (P < 0.01). CONCLUSION: Among 2713 college
      students, about 1/3 adolescents having experienced self-harm in the last 6
      months, many with repeated ones. Depression and difficulties in identifying
      feelings were the two risk factors while self-esteem was the protective factor
      related to most of the self-harm cases.

PMID- 21176691
TI  - [Integrated detection and analysis on the clusters of schistosomiasis based on
      geographic information system].
AB  - OBJECTIVE: To detect and analyze the clusters of schistosomiasis on marshland and
      lake areas based on geographic information system (GIS) in 2008 and to provide
      suggestions for the development of integrated methodology on the detection of
      clusters on related diseases. METHODS: Moran's I of global spatial
      autocorrelation, Getis-Ord Gi of local spatial autocorrelation and SaTScan were
      used to detect the schistosomiasis clusters based on GIS and comparison of the
      results for different methods were performed. RESULTS: Results from the global
      Moran's I tests for all the marshland and lake areas related to the
      schistosomiasis were statistically significant (P < 0.05) and indicated spatial
      heterogeneity;the z-score outcomes as calculated by Getis-Ord Gi indicated high
      cluster that 50 clusters were categorized at the 0.05 significance level and the
      z-score of these 45 clusters were more than 0. Results of SaTScan statistics
      appeared the same as local spatial autocorrelation and almost showing the
      existence of 5 cluster areas. CONCLUSION: The geographical distribution of
      clusters where schistosomiasis was prevalent showed that it was closely
      corresponded to the middle and lower Yangtse river and in particular, many
      clusters were located near the boundary of Hubei and Hunan province.

PMID- 21176692
TI  - [Spatial analysis on new smear-positive pulmonary tuberculosis in China, 2003 -
      2008].
AB  - OBJECTIVE: To analyze the notification status on new sputum-smear positive
      pulmonary tuberculosis (TB) over the recent years in China, and identify the
      clusters to address the related reasons. METHODS: To spatially and temporally
      scan the data regarding notification, and to display the results via geographic
      information system. RESULTS: (1) Spatial analysis identified 6 clusters and their
      relative risks ranged from 1.03 to 1.83 with statistical significance; (2)
      Temporal analysis identified there were clusters between 2005 and 2007 in terms
      of notification on new sputum-smear positive pulmonary TB, and the relative risk
      was 1.27 (P = 0.001); (3) Spatial and temporal analysis identified 2 clusters and
      the relative risks of the first class cluster and the second class cluster were
      1.35 and 1.49 respectively with statistical significance. Provinces included in
      the first class cluster were basically the same as these in spatial analysis.
      CONCLUSION: Distribution of the notification on new sputum-smear positive
      pulmonary TB was not stochastic at space, time and space-time, and clusters did
      exist in China.

PMID- 21176693
TI  - [Epidemiological investigation on endemic fluorosis along the Yellow River
      alluvial plain of Shandong province].
AB  - OBJECTIVE: To investigate the current prevalent status of endemic fluorosis in
      the floodplain area of the lower Yellow River in Shandong province. METHODS:
      According to "The National Technical Scheme for Endemic Disease Control in 2008",
      16 counties were chosen to carry out the epidemiological survey of endemic
      fluorosis. Three villages were chosen in each county, to determine the fluoride
      content of drinking water and to check the dental fluorosis of children aged 8 to
      12 year old, the skeletal fluorosis of adults over 16 years of age. Both children
      and adults were tested for urine fluoride. The content of fluoride in drinking
      water and urine was determined by F-ion selective electrode while dental
      fluorosis of children aged 8 to 12 years old was diagnosed by Dean's method and
      adults skeletal fluorosis by the National Standard for "Diagnosis of endemic
      skeletal fluorosis" (WS 192-2008). RESULTS: The investigation was taken place in
      26 'improved-water-quality' villages in 16 counties, among which 19 villages had
      water fluoride content <= 1.00 mg/L and accounted for 73.08% (19/26), 7 villages
      had water fluoride content > 1.00 mg/L and accounted for 26.92% (7/26), with the
      highest water fluoride content as 3.73 mg/L. In 22 'yet to improve-water quality'
      villages in 16 counties, 5 villages had water fluoride content <= 1.00 mg/L
      (accounted for 22.73%), 17 villages had water fluoride content > 1.00 mg/L
      (accounted for 77.27%), with the highest water fluoride content as 3.38 mg/L. The
      overall rate of dental fluorosis among children aged 8 to 12 years old was 52.18%
      (1042/1997), with the index of dental fluorosis as 1.17 and the rate of dental
      damage as 8.01% (160/1997). The urinary fluoride values above 1.40 mg/L were
      found in 65.00% (845/1300) of children aged 8 to 12 years old, with the highest
      urinary fluoride concentrations as 18.53 mg/L. The rate of skeletal fluorosis by
      clinic and X-rays in adults older than 16 years old were 4.35% (1121/25 781) and
      11.36% (5/44), respectively. The urinary fluoride values above 1.60 mg/L were
      found as 63.92% (606/948) in adults older than 16 years old, with the highest
      urinary fluoride concentrations as 21.35 mg/L. CONCLUSION: The status of endemic
      fluorosis had not been effectively controlled and the situation for endemic
      fluorosis control was still critical in the floodplain area of the lower Yellow
      River in Shandong province, suggesting that the preventive approaches on endemic
      fluorosis control should be strengthened.

PMID- 21176694
TI  - [An outbreak of gastroenteritis caused by contaminated well water in a village,
      Henan province].
AB  - OBJECTIVE: To identify the cause and mode of transmission of a gastroenteritis
      outbreak in a village, Henan province. METHODS: Gastroenteritis patients were
      identified through family visits, interviewing the village doctors and reviewing
      diagnosis and prescription records at the village health clinic. Cases were
      defined as onset of one of the four symptoms from the village resident during
      July 20 to August 12, 2010. The symptoms would include diarrhea (>= 3 times/day),
      abdominal pain, nausea or vomiting. A retrospective cohort study was conducted to
      assess the association between drinking raw well water or eating noodles rinsed
      by raw well water and gastroenteritis. Stools or vomits of the case-patients and
      the well water samples were tested for bacterial pathogens. RESULTS: Data for 60
      case-patients were collected. All cases occurred in the northern part of the
      village. Persons who used water from a public well in the northern part of the
      village had an attack rate of 55%, which was 3.5 times of those who did not use
      the well water (16%) (RR = 3.5, 95%CI: 1.2 - 10). Results from the retrospective
      cohort study showed that drinking un-boiled water from the well was a risk factor
      (RR = 1.7, 95%CI: 1.3 - 2.3). Laboratory testing showed that total coliform and
      E. coli both greatly exceeded the limit considered safe for drinking, indicating
      there was fecal contamination in the well water. No bacterial pathogens were
      detected in the patients' stools or vomits. CONCLUSION: The outbreak was mainly
      caused by drinking contaminated water from the public well in the northern part
      of the village.

PMID- 21176695
TI  - [Relationship between genetic polymorphism of ERCC1 and susceptibility to liver
      cancer].
AB  - OBJECTIVE: To investigate the association between genetic polymorphisms of ERCC1
      C8092A and susceptibility to liver cancer, as well as the gene-environmental
      interaction on the etiology of liver cancer in Fuzhou. METHODS: A case-control
      study was conducted to collect the information on environmental exposure while
      genetic polymorphism of ERCC1 was analyzed by the polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) method. General relative risk
      regression models were further applied to fit the interaction between genetic
      polymorphisms of ERCC1-C8092A and the environmental factors of liver cancer.
      RESULTS: ERCC1-C8092A variant genotypes were associated with significant
      increasing risk of liver cancer adjusted odds ratio (OR = 3.789, 95%CI: 2.792 -
      5.142), compared to the wild-type homozygote. Data from the analysis of
      interaction showed that genetic polymorphism of ERCC1-8092A appeared super
      additive interaction with drinking pond-ditch or with hepatitis B, and super
      multiplicative interaction with eating moldy food. CONCLUSION: The point mutation
      in ERCC1-8092A was possibly susceptible to liver cancer, and related
      synergistically with other risk factors in hepatocelluar carcinogenesis in
      Fuzhou.

PMID- 21176696
TI  - [Analysis on the correlation between SF-36 and QOL-35 in patients and coronary
      artery disease].
AB  - OBJECTIVE: To analyze the correlation between SF-36 and QOL-35 and the
      consistency of the two kinds of life-quality questionnaires when evaluating the
      quality of life in patients with coronary heart disease. METHODS: 781 in-hospital
      patients, who underwent coronary angiography from June 2008 to April 2009, were
      included in this study. Quality of life was measured by the Chinese versions of
      SF-36 and QOL-35. Demographic and clinical information were collected.
      Correlation Analysis was done between SF-36 and QOL-35 in the patients with
      coronary artery disease. RESULTS: The total score of SF-36 was 62.63 +/- 12.47
      and the QOL-35 total score was 62.70 +/- 9.69. Data from the simple correlation
      analysis showed that SF-36 and QOL-35 total scores (r = 0.725, P < 0.01), SF-36
      physical functioning and QOL-35 independent living capacity (r = 0.933, P <
      0.01), SF-36 mental health and QOL-35 mental health(r = 0.132, P < 0.01), SF-36
      social function and QOL-35 social function score (r = 0.215, P < 0.01) were all
      relevant. Canonical correlation analysis showed that there was significant
      correlation between SF-36 and QOL-35 (r = 0.946, P < 0.01). CONCLUSION: SF-36 and
      QOL-35 were consistent in the evaluation on the quality of life, at the overall
      level.

PMID- 21176697
TI  - [Evaluation on the accuracy of high-frequency ultrasound being used in the breast
      cancer screening program in women from Asian countries: a systematic review].
AB  - OBJECTIVE: To evaluate the accuracy and value of high-frequency ultrasound for
      breast cancer screening in Asian women. METHODS: Published studies on high
      frequency ultrasound for screening breast cancer in Asian women were systemically
      searched and assessed by the Quality Assessment of Diagnostic Accuracy Studies
      (QUADAS) tool. Meta-DiSc 1.4 software was used for extracting data, calculating
      the summary sensitivity and specificity, and drawing the Summary Receiver
      Operating Characteristic (SROC) curve. Furthermore, the proportion of screening
      of diagnosis on early breast cancer (TNM stage 0, I and II) by high-frequency
      ultrasound was calculated. RESULTS: Seven screening studies including 22 244
      women were selected for Meta-analysis. According to the QUADAS items, 5 studies
      were classified as A degree and 2 studies were evaluated as B degree. For study
      in the heterogeneous of these 7 studies (Q = 38.97, P < 0.0001), Random Effects
      Model (REM) was selected. The combined sensitivity (95%CI) and specificity
      (95%CI) were 0.785 (0.726 - 0.837) and 0.975 (0.973 - 0.977) respectively. The
      Area Under the Curve (AUC) of SROC was 0.9800. Among the follow-up studies of
      following period over one year, 96.9% of the diagnosed patients with breast
      cancer were at clinical stage II or prior to it. CONCLUSION: Because of its high
      accuracy, high-frequency ultrasound could be recommended for screening breast
      cancer in Asian women.

PMID- 21176698
TI  - [Association between air particulate matter and stroke attack or mortality: a
      Meta-analysis].
AB  - OBJECTIVE: To analyze the associations between particulate air pollution (PM(10),
      PM(2.5)) and stroke daily attack or mortality. METHODS: Meta-analysis method was
      used to polysynthetically analyze 16 quantitative studies about the associations
      between particulate air pollution and stroke daily attack or mortality. The
      relative odds ratio (OR)of stroke attack or mortality associated with per 10
      ug/m(3) increase of particulate matter concentration was used as effective value,
      taking a sensitivity analysis for the results. RESULTS: A 10 ug/m(3) increase in
      PM(10) was associated with a 1.09% (95%CI: 0.10% - 2.08%) increase in stroke
      daily attack (OR = 1.011, 95%CI: 1.001 - 1.021) and 0.70% (95%CI: 0.60% - 0.80%)
      increase in stroke daily mortality (OR = 1.007, 95%CI: 1.006 - 1.008). The
      results of sensitivity analysis supported above results. As for PM(2.5) OR
      appeared to be 1.001 (95%CI: 0.992 - 1.010) with a 10 u g/m(3) increase in stroke
      daily attack and 1.052 (95%CI: 0.958 - 1.154) for daily mortality. CONCLUSION:
      There are positive associations between PM(10) and stroke daily attack and
      mortality, increase of PM(2.5) was not associated with stroke attack and
      mortality.

PMID- 21176699
TI  - [A study regarding the applicability of WSARE algorithms in the early warning
      system of infectious disease outbreaks].
AB  - To investigate the application of WSARE (What's Strange About Recent Events)
      algorithm in early warning on outbreaks of infectious diseases and to explore the
      multi-dimensional statistical methods for the detection of infectious diseases
      outbreak. Using WSARE algorithms based on historical data and Bayesian Network as
      baseline respectively, to analyze data on measles by mimicking the real-time
      monitoring and early warning system in Bao'an district, Shenzhen city, in 2007.
      WSARE algorithms were considered to be effective and timely in detecting the
      abnormally increase of measles among special population. WSARE algorithm could
      timely detect the abnormal increase of diseases among special local populations,
      thus having important value in the application of early warning system during the
      outbreak of infectious diseases.

PMID- 21176700
TI  - [A review of cardiovascular disease prediction model at home and abroad].

PMID- 21176701
TI  - [A review on pathogenesis of human granulocytic Anaplasma].

PMID- 21176702
TI  - [Sociotherapeutic interventions--sufficiently available?].

PMID- 21176703
TI  - [Outlines of interdisciplinary addiction research given by the example of medical
      imaging with PET, SPECT and fMRI regarding effects of psychotropic substances].
AB  - The addiction phenomenon provides a fertile ground for the application of the
      tools of medical imaging which contribute to the development of scientific
      conceptualization of the effect of psychotropic substances. Medical imaging as
      for instance PET (Positron Emission Tomography), SPECT (Single Photon Emission
      Tomography) or functional Magnetic Resonance Imaging (fMRI) are well established
      for the examination of functional activity in the living brain. Medical imaging
      permits the development of functional activation maps during perceptual,
      cognitive or emotional efforts with a high temporal and spatial resolution.
      Medical imaging devices have therefore also been used to help our understanding
      of many aspects of the pharmacokinetics and pharmacodynamics of abused drugs.
      Because Delta-9-Tetrahydrocannabinol and cocaine continue to be the most commonly
      used illicit drugs, their effects on the brain function are of major interest.
      The cannabinoid CB(1) receptor agonist Delta(9)-THC as for instance has also been
      suggested for treatment of Tourette syndrome (TS). This article provides an
      overview of present applications of medical imaging with PET, SPECT, and fMRI and
      its results regarding addiction-related research on Delta-9-Tetrahydrocannabinol
      and cocaine.

PMID- 21176704
TI  - [Regarding the search for a specific neuropsychological profile in depression:
      limits and perspectives].
AB  - It has long been known that patients with depression show neuropsychological
      symptoms. A great number of studies aimed at an exact characterization of these
      symptoms. Scientifically, the knowledge about such a profile was thought to
      provide information about neurobiological dysfunctions. Clinically, this
      knowledge would be useful to differentiate depression from other psychiatric or
      neurological diseases. However, the neuropsychological profile of depression is
      still not well established. We discuss four perspectives that provide possible
      explanations for the current state of knowledge and may help to further develop
      our knowledge about neuropsychological dysfunctions in depression: first, because
      there is great variation in the aetiology and phenomenology of depression and
      even in different subtypes of affective disorders, unitary neuropsychological
      profiles can not be expected. Further research should focus on relevant factors
      that influence cognitive functioning of depressed patients. Second,
      neuropsychological tests administered should be specific for certain cognitive
      functions and, third, should provide emotionally relevant stimuli as well.
      Finally, future studies should systematically consider psychiatric control groups
      in addition to healthy participants. With the consideration of these factors,
      neuropsychological research in depression significantly contributes to our
      understanding and conceptualization of mental disorders.

PMID- 21176705
TI  - [Clinical and social risk factors for the readmission of patients with
      schizophrenia to psychiatric inpatient care: a long-term analysis].
AB  - BACKGROUND: In recent years, admission rates to psychiatric inpatient care have
      steadily increased, whilst the number of beds has progressively decreased, at
      least in german-speaking countries. A better understanding of risk factors
      concerning psychiatric readmissions is indispensable in order to avoid
      unnecessary inpatient treatment. The aim of our study was to test the influence
      of various clinical and social factors on the time to readmission. METHOD: We
      analysed data of an observational study considering especially vulnerable
      patients with schizophrenia (N = 103). We applied multivariate time-hazards
      models (survival analysis) to examine the predictors of the time to readmission
      within 12 months. Independent variables were either time-varying (e.g. Needs for
      care Assessment Scale (NCA)) or time-invariant (e.g. age). RESULTS: About 50% of
      the patients were readmitted during the observation period, many of them within
      the first few weeks. In the final models clinical needs, and a social need
      increased the risk of readmission, whereas the use of neuroleptic medication
      reduced the risk. There was an interaction effect between social support and
      time. CONCLUSIONS: Both, clinical and social factors influence the risk of
      psychiatric readmission. Therefore, the prevention of readmissions should focus
      on the patients' skills to manage his/her illness and on the social support that
      the patients receive.

PMID- 21176706
TI  - [Etiological illness concepts in patients suffering from schizophrenia from
      Austria and Pakistan with special consideration of the gender aspect].
AB  - OBJECTIVE: Etiological illness concepts of patients with schizophrenia are an
      important factor for the drug compliance as well as for a successful
      psychotherapeutic approach. These cognitive representations are influenced by
      issues like the illness, culture, gender, and age. The aim of this study was the
      elaboration of the interaction of these factors with special consideration of the
      gender aspect. METHOD: The notions about the reasons of illness were explored by
      means of a 41-item standardized self-rating instrument in 240 patients suffering
      from schizophrenia from Pakistan and Austria. RESULTS: Only in the scale
      "conflicts" the mean values for Austrian women were statistically significant
      higher than for their male counterparts. In Pakistani patients we found no
      significant differences, patients with an early age at onset of illness more
      frequently reported a magic-religious explanatory model in both cultures.
      Austrian patients with a longer duration of illness believed more often that the
      outbreak of the illness was caused by negligent behaviour. CONCLUSION: While
      gender has important effects on course and outcome of schizophrenia, the
      influence on etiological illness concepts is rather weak. Two reasons can be
      postulated: (a) The acquirement of knowledge about the development of mental
      disorders is culture-specific, but not gender-specific, (b) psychotic disorders
      are even out originally existing gender differences.

PMID- 21176707
TI  - [Assessment of overinclusion in schizophrenia by a computer-assisted version of
      the Concept Overinclusion test].
AB  - OBJECTIVE: A special form of formal thought disorder is the overinclusion in
      schizophrenia. The Begriffsumfangstest (BUT, Concept Overinclusion test) is a
      neuropsychological test for the assessment of this phenomenon. The test is
      available in a paperand- pencil version since the 1990s and now available in a
      computerized version. The aim of this study was a replication of the paper-and
      pencil version with the computerized version of the test and also the detection
      of putative correlations with ego-psychopathology. METHODS: 40 patients with
      schizophrenia and 16 healthy controls were assessed with the BUT and with a scale
      for the assessment of ego-psychopathology (IPP). The tests were performed on five
      different time points with intervals of approximately two weeks. RESULTS: The BUT
      parameters for the group of patients and the control group differed
      significantly. Several positive correlations were found between he values of the
      BUT and the IPP. CONCLUSION: The computerized Version of the BUT is also
      applicable for the detection of overinclusion. The relation between overinclusion
      as a semantic dysfunction and ego-psychopathology may lead to further
      psychopathological investigations concerning schizophrenic thought disorders.

PMID- 21176708
TI  - [Gender aspects of psychiatric publications].
AB  - OBJECTIVE: Are authors of German language psychiatric journals more often male or
      female? Are there gender differences regarding scientific topics? METHODS:
      Analysis of publications of two German-language journals (Neuropsychiatrie,
      Psychiatrische Praxis) for the period 2008-2009. RESULTS: We could not find any
      gender differences concerning the number of first authors, but the number of male
      co-authors was nearly double as high as of female co-authors. Qualitative
      research methods were used more often by female researchers, but there were no
      significant differences regarding scientific topics. CONCLUSIONS: Overall, we
      found fewer gender differences than expected concerning authorship.

PMID- 21176709
TI  - [On the issues of neuroenhancement].

PMID- 21176710
TI  - Clinical neuropathology, 1/2011.

PMID- 21176711
TI  - Unclassifiable tauopathy associated with an A152T variation in MAPT exon 7.
AB  - Mutations in the microtubule-associated tau (MAPT) gene are associated clinically
      with frontotemporal dementia with or without supranuclear palsy, corticobasal
      syndrome or parkinsonism. Here we present clinical, neuropathological, genetic
      and biochemical data on a patient with an A152T variation in exon 7 of MAPT. A 63
      year-old man presented with memory disturbance and later speech disorder,
      followed by progressive dementia and terminally myoclonus together with periodic
      sharp waves in EEG. Duration of illness was 5 years. Similar neuropsychiatric
      symptoms were reported in the patient's father. Neuropathological evaluation
      revealed neuronal loss mainly in the frontal and temporal cortices and substantia
      nigra. Abundant phospho-tau immunoreactive thread-like structures and diffuse
      staining of neuronal cytoplasm predominated in the frontal and temporal cortex,
      and hippocampus. There was a lack of astrocytic plaques and tufted astrocytes,
      and only a moderate number of oligodendroglial coiled bodies were seen. Tau
      pathology was characterized by the 4R tau isoform; immunoblot revealed bands at
      64 and 68 kDa, and ultrastructure of filaments was compatible with twisted
      ribbons. Pathogenic mutations have not been reported in exon 7. Our observation
      of an apparently familial disorder with a novel neuropathological phenotype
      suggests a possible pathogenic role of this MAPT gene variation, which might be
      different from mutations affecting the microtubule binding.

PMID- 21176713
TI  - Annexin-1 is no useful surrogate marker of multiple sclerosis - an
      immunocytochemical study of the cerebrospinal fluid.
AB  - OBJECTIVE: Annexin-1 is a calcium-binding protein with anti-inflammatory
      properties, which has previously been described in MS plaque tissue. We
      investigated the feasibility and specificity of annexin-1-immuncytochemistry of
      CSF cells to test its potential as a surrogate marker for MS. MATERIALS AND
      METHODS: CSF-specimens of 49 MS cases with different courses and 94 control cases
      were immunocytochemically studied with a monoclonal antibody to annexin-1.
      RESULTS: The highest level of cytoplasmic immunoreaction was seen in the most
      acute inflammatory disorders, such as bacterial meningitis and neuroborreliosis.
      CIS-, RR-MS-, and viral meningoencephalitis cases came next. The lowest annexin-1
      expression was observed in neurosyphilis and SP-MS. In PP-MS and non-inflammatory
      control cases, annexin-1 expression was entirely lacking. CONCLUSION:
      Immunocytochemical staining of CSF cells with an antibody to annexin-1 is
      feasible. This may be helpful in further study of its role in the pathophysiology
      of inflammatory CNS diseases. The expression pattern seems to rather reflect the
      acuteness of the inflammatory process than specifying a certain underlying
      pathology. Although differences were observed between diverse disease groups,
      because of considerable overlap, a certain diagnosis of an individual case cannot
      be achieved. Thus, at present, we cannot recommend annexin-1 as a reliable
      surrogate marker of MS.

PMID- 21176712
TI  - Churg-Strauss syndrome complicated by neuropathy: a clinicopathological study of
      nine cases.
AB  - OBJECTIVE: The purpose of this study was to investigate the clinical,
      electrophysiological and pathological features of Churg Strauss syndrome (CSS)
      neuropathy. METHODS: Biopsies were selected from over 700 sural nerve biopsies.
      The diagnosis of vasculitis was based on established clinicopathological
      criteria. Complete laboratory, clinical, electrophysiological and pathological
      studies were performed in all cases. RESULTS: Nerve biopsies of 9 patients were
      diagnosed as Churg-Strauss syndrome. The pathological features were vasculitis
      with predominant axonal degeneration and a varying pattern of myelinated fiber
      loss. The vasculitic changes were found mainly in small epineural blood vessels.
      Mononeuritis multiplex and distal symmetrical and asymmetrical sensorimotor
      neuropathy, were equally frequent. CONCLUSION: We conclude that, Churg-Strauss
      syndrome complicated frequently with polyneuropathy, and as remission depends on
      immunosuppressive therapy, it is important to recognize it in the early stage.
      The diagnosis of polyneuropathy is based on clinical and electrophysiologic
      studies, but precise histology, immunolohistochemistry and morphometric study of
      the peripheral nerve biopsy may be decisive in establishing the diagnosis.

PMID- 21176714
TI  - Unusual localization of an unusual tumor: calcifying pseudoneoplasm of the
      foramen magnum.
AB  - OBJECTIVE: We report a rare case of calcifying pseudoneoplasm in the foramen
      magnum. A large variety of tumors can be found in the foramen magnum;
      meningiomas, neurofibromas, chordomas, chondrosarcomas and metastases are among
      those that have been reported. Based on the histopathological structure of the
      tumor, radical excision or, in the case of tumors with good behavioral pattern,
      only decompressive debulking can be applied, in an effort to avoid unnecessary
      morbidities. Thus, it is important to know the nature of the tumor before
      planning the surgery. CASE REPORT: A 53-year-old man with a 1-year history of
      pain on the left side of his face was admitted to our service. Magnetic resonance
      imaging revealed a calcific mass at the left side of the spinal cord at the level
      of the foramen magnum. Median suboccipital craniectomy and total tumor resection
      were performed and there was no additional neurological deficit postoperatively.
      CONCLUSION: We report, to our knowledge, the second case of a calcifying
      pseudoneoplasm of the foramen magnum. We emphasize that these tumors are
      pathologically benign and do not require aggressive surgical treatment and
      suggest that asymptomatic cases can be followed radiologically.

PMID- 21176715
TI  - Cerebral coenurosis mimicking hydatid disease - report of two cases from South
      India.
AB  - Coenurosis, a rare zoonotic disease caused by the larval form of Taenia multiceps
      (bladderworm) is common in sheep rearing countries, but human infections are
      rare. Central nervous system involvement produces large giant sized cysts that
      radiologically closely mimic hydatid cysts. Most human infections resulting in
      cerebral coenuri have been reported from Europe and Africa. We report two cases
      of cerebral coenurosis from India, the first in a 55-year-old male presenting
      with a large cystic lesion in the right parietooccipital region and the second
      occurring in a 36-year-old male involving the left temporal trigonal region, that
      radiologically closely mimicked hydatid cyst. Histopathologic examination
      revealed characteristic features of coenuri with multiple protoscolices
      invaginating into a large cyst lined by outer cuticular layer. Awareness of this
      rare parasitic infestation is important to discriminate from the more common
      hydatid and giant cysticercal cysts.

PMID- 21176716
TI  - Erythropoietin receptor expression in normal and neoplastic choroid plexus.
AB  - BACKGROUND: The erythropoietin receptor (EpoR) is expressed widely throughout the
      human CNS, including the choroid plexus. Recent studies have shown that EpoR is
      also expressed in various human tumors, including carcinomas, meningiomas and
      gliomas. Thereby, the Epo-EpoR pathway plays a role in inhibition of apoptosis
      and tumor growth, infiltration, angiogenesis and metastasis as well as treatment
      resistance and is a potential target in oncological treatment. Lower levels of
      EpoR have been associated with shorter survival in high grade gliomas and higher
      risk of tumor recurrence in meningiomas. METHODS: Since the EpoR status in human
      choroid plexus tumors (CPT) is not known, we investigated 57 CPT from 43 cases
      including 14 recurrent tumors and compared them with 23 samples of normal choroid
      plexus (CP). CPT samples consisted of choroid plexus papillomas/CPP (n = 41),
      atypical CPP (n = 15) and choroid plexus carcinoma/CPC (n = 1). EpoR expression
      was determined by immunohistochemistry using semi-quantitative scoring for
      staining intensity and was validated in exemplary cases using western blot and RT
      PCR. RESULTS: EpoR expression was observed in all samples of normal and
      neoplastic CP with significantly lower expression levels in CPT (p < 0.001).
      CONCLUSION: No significant correlation was found between EpoR expression and age,
      gender, WHO grade, number of mitosis or tumor recurrence. EpoR expression in CPT
      is in line with its expression in normal CP and with previous reports on EpoR
      expression in other glial neoplasms. Association of EpoR levels in CPT with
      survival, as known in astrocytic gliomas, remains to be determined.

PMID- 21176717
TI  - Unusual fibrous meningioma in a patient with sarcoidosis: central necrosis
      associated with multinucleated giant cells.

PMID- 21176718
TI  - Toxic dermatitis in patients treated with Taxotere (docetaxel): three case
      reports.

PMID- 21176719
TI  - The pharmacokinetics and safety of desvenlafaxine in subjects with chronic renal
      impairment.
AB  - BACKGROUND: Desvenlafaxine (administered as desvenlafaxine succinate), the major
      active metabolite of venlafaxine, is a new serotonin-norepinephrine reuptake
      inhibitor (SNRI) approved for the treatment of major depressive disorder (MDD).
      OBJECTIVE: To assess the pharmacokinetics, safety, and tolerability of
      desvenlafaxine in healthy volunteers vs. those with renal impairment. MATERIALS
      AND METHODS: A single, oral, 100 mg dose of desvenlafaxine was administered to
      healthy subjects (n = 8) and subjects with mild (n = 9), moderate (n = 9), or
      severe (n = 7) renal impairment (24-h creatinine clearance, ml/min: 50 - 80, 30 -
      50, or < 30 ml/min, respectively) or end-stage renal disease (ESRD; on dialysis.

PMID- 21176720
TI  - An assessment of teicoplanin use and monitoring serum levels in a Chinese
      teaching hospital.
AB  - OBJECTIVE: To validate a high performance liquid chromatography (HPLC) method for
      serum teicoplanin measurement and use the method for clinical monitoring of
      teicoplanin levels to analyze the clinical application of teicoplanin. METHODS:
      55 patient profiles were collected and analyzed for the clinical teicoplanin
      application. 10 critically ill patients of the 55 cases were monitored for
      teicoplanin trough concentration using the HPLC method. RESULTS: The modified
      HPLC method exhibited excellent linearity, with correlation coefficient r =
      0.9995. The intra-day and inter-day coefficients of variation were less than 10%.
      The lower limit of detection of teicoplanin was 5.63 mg/l. The recovery of
      teicoplanin was above 90%. Of the 55 patients in this study, there were 42
      patients without load-dosing. There were only 29 patients treated with
      teicoplanin documented Gram-positive infections by etiological diagnoses. In the
      10 patients with teicoplanin serum trough concentration monitoring, all cases
      received a loading dose of 400 mg every 12 h for 3 doses, and the mean trough
      concentration of teicoplanin was 10.82 +/- 4.51 mg/l. The mean trough levels were
      13.04 +/- 6.23 mg/l in 4 patients with microbiological eradication and
      improvement of symptoms of diseases and 9.34 +/- 2.61 mg/l in 6 patients with
      persistence of previous clinical infectious symptoms, respectively. CONCLUSION:
      The modified HPLC method is robust, highly reproducible and suited to monitor the
      concentration of teicoplanin. In critically ill Chinese patients, we should
      consider more appropriate loading doses and evaluate the relationship between
      teicoplanin trough concentration and the efficacy using microbiological and
      clinical parameters.

PMID- 21176721
TI  - Contribution of 1173C > T polymorphism in the VKORC1 gene to warfarin dose
      requirements in Han Chinese patients receiving anticoagulation.
AB  - OBJECTIVE: The objective was to assess 1173C > T polymorphism of the VKORC1 gene
      and its contribution to warfarin dose requirements in Han Chinese patients.
      METHODS: Blood samples were collected from 178 patients with stable warfarin dose
      requirements and an international normalized ratio (INR) of the prothrombin time
      within the target range (1.5 - 3.0). Polymorphisms for VKORC1 (1173C > T),
      CYP2C9, venous INR, and plasma concentration and unbound concentration of
      warfarin were analyzed. RESULTS: VKORC1 (1173C > T) genotyping showed that 154
      patients were homozygous TT, 23 were heterozygous CT, and one was homozygous for
      the CC genotype. Patients with the VKORC1 (1173CC + CT) genotype required a
      significantly higher warfarin dose (3.33 +/- 1.04 mg/day) than those with 1173TT
      (1.81 +/- 0.63 mg/day; p < 0.001). The multiple linear regression model for
      warfarin dose indicated significant contributions from the VKORC1 (1173C > T)
      genotype (r2 = 0.355; p < 0.001), and age, body weight, and CYP2C9 and VKORC1
      genotype together (r2 = 0.513; p < 0.001). The two SNPs (-1639 and 1173) were
      found to be in very strong linkage disequilibrium with estimated D' = 0.96 (95%CI
      (0.83 - 0.99)). CONCLUSION: The VKORC1 (1173C > T) polymorphism might be very
      important, and its contribution can be equally explained by the VKORC1(-1639 G >
      A) polymorphism for warfarin dose requirements in Han Chinese patients.

PMID- 21176722
TI  - The possibility of using the specific RIA method for the area-under-time
      concentration curve sparse sampling calculation of cyclosporin A despite a large
      post-dose overestimation.
AB  - OBJECTIVE: To find limited sampling strategies (LSS) for prediction of the real
      AUC using the RIA analytical method. METHOD: Blood samples of 40 male renal
      transplant patients taken pre-dose and after 0.5, 1, 1.5, 2, 3, 5, 8, and 12 h in
      the steady-state were analyzed with HPLC and the specific RIA method. I. Eight
      equations for AUC0-12 and one for AUC0-8 obtained from the literature, that
      produced the mean percentage prediction error (%PE) < +/- 15% and absolute %PE <
      30% in 95% of predictions, were analyzed for possibility to predict the real AUC
      of CsA. II. Multiple regression analysis (MRA) was provided for the AUC equation
      proposal. Patients were divided into two groups according to the AUC0-12. Group I
      was used for LSS : s proposals while Group II for validation. The bias and
      precision were expressed as %PE, r2 and RMSE. The relationship of %PE interassay
      and with LSS:s was expressed as Pearson correlation r. GraphPad InStatt Software
      was used for MRA and Pearson r calculation. RESULTS: None of the equations
      described in the literature predicts AUC of CsA proprietarily. Seven equations
      for AUC0-12 and five for AUC0-8 were proposed with MRA for prediction of real AUC
      from RIA values. CONCLUSIONS: LSS:s can moderate the interassay %PE in AUC of
      CsA. New patients should be tested with both RIA and HPLC for the level of
      overestimation. The conversion factors should be calculated for patients with an
      overestimation higher than 90%. Our equation 251.09 + 0.5195 * C1h + 4.926 * C3h
      or 196.13 + 4.526 A?* C0h + 2.089 * C1.5h for AUC0-12, and 171.80 + 0.4759 * C1h
      + 4.132 * C3h for AUC0-8 may be used in patients with medium or low RIA and HPLC
      differences. Repeated analysis with HPLC is thus suggested in cases with AUC:s
      results close to the lower or upper margin of the therapeutic window.

PMID- 21176723
TI  - Subacute liver failure induced by adalimumab.
AB  - Most cases of liver toxicity associated with TNF-antagonists have been linked to
      infliximab and to a lesser extent to etanercept. So far only mild elevations of
      liver enzymes during therapy with adalimumab have been reported. In general,
      patients who developed ALT and AST elevations were asymptomatic and the
      abnormalities decreased or resolved with either continuation or discontinuation
      of adalimumab, or modification of concomitant medications. In this case report,
      we are presenting the first case of a patient without previous history of liver
      disease or concomitant risk factors for liver disease who developed subacute
      liver failure during therapy with adalimumab for psoriatic arthritis.

PMID- 21176724
TI  - Erdosteine affects eicosanoid production in COPD.
AB  - Oxidant-antioxidant imbalance and lipid peroxidation are known to activate the 5
      LO pathway with increased expression of inflammatory eicosanoids. Erdosteine has
      recently shown important anti-oxidant properties, including the ability to reduce
      8-isoprostane in COPD patients. AIM: To assess the effects of erdosteine (E) on
      eicosanoids, and to compare the time-course of effect with that of E anti-oxidant
      activity. METHODS: 12 moderate COPD patients (9 males, 60 - 78 y) randomly
      received E 300 mg b.i.d. or placebo (P) for 10 days in a double-blind, controlled
      design. Blood ROS (Fort/Units); serum LTB4 and urine LTE4 (pg/ml) were measured
      at baseline and after 1, 3, 5 and 10 days of treatment. Analysis of covariance
      (ANCOVA) was performed. RESULTS: In COPD patients, both LTB4 and LTE4 dropped
      significantly during the 10-day treatment with E: s-LTB4 from 136.0 +/- 35.4 SD
      to 54.5 +/- 31.2 SD; u-LTE4 from 267.0 +/- 91.5 SD to 84.0 +/- 64.7 SD, p < 0.001
      vs. p from Days 5 and 3, respectively. Moreover, a significant decrease of blood
      ROS was confirmed in patients using E. FEV1 values slightly increased during
      erdosteine treatment, whereas a trend to decrease was observed in the placebo
      group, with a significant difference in favor of erdosteine after 10 days of
      treatment (p = 0.0088). CONCLUSIONS: 1) The scavenging and anti-inflammatory
      effects of Erdosteine were both confirmed; 2) erdosteine proved to affect
      eicosanoids significantly; 3) this novel effect underlines the important anti
      inflammatory potentialities of the drug in COPD; 4) further investigation is
      needed in order to assess the capability of Erdosteine in controlling ongoing
      inflammation in chronic respiratory diseases.

PMID- 21176726
TI  - Minocycline-induced chemical pneumonitis and its successful treatment: a case
      report.
AB  - Chemical pleurodesis is an effective treatment for persistent air leakage and
      secondary pneumothorax. We report the case of a 57-year-old man who presented
      with pneumothorax and was treated by tube thoracostomy. Because of malpositioning
      of the chest tube, the minocycline that was administered for pleurodesis was
      injected into the lung parenchyma instead, which induced chemical pneumonitis. A
      review of literature indicated that this is the first report of minocycline
      associated chemical pneumonitis and its successful treatment.

PMID- 21176725
TI  - Toxic dermatitis in patients treated with Taxotere(r) (docetaxel): three case
      reports.
AB  - Three out of 25 patients receiving the same batch docetaxel, developed toxic
      dermatitis within 5 days after administration. Timing of occurrence was equal and
      symptoms were similar. Two patients continued with docetaxel without any
      problems. There is no assignable cause found that could explain the toxic
      dermatitis.

PMID- 21176727
TI  - High absolute bioavailability of the new oral phosphodiesterase-4 inhibitor
      roflumilast.
AB  - OBJECTIVE: To establish basic intravenous (IV) pharmacokinetics of roflumilast
      (ROF) and its pharmacologically active metabolite roflumilast N-oxide (R-NO) and
      to determine the absolute bioavailability of ROF in humans. MATERIALS: In a
      randomized, open-label, 2-period, 2-sequence crossover study 12 healthy male
      subjects were randomized to receive ROF either orally (PO) 500 ug (immediate
      release tablets) or single IV (150 ug over 15 min). Plasma concentrations were
      determined. Dose-adjusted point estimates and 90% confidence intervals (CI) were
      calculated for the ratio of the AUC time curves using a multiplicative model and
      parametric analysis. RESULTS: After IV administration, clearance of ROF was 0.14
      l/h/kg, volume of distribution (Vd area) 2.92 l/kg, and the terminal t1/2 was
      14.8 h. After PO administration, ROF was rapidly absorbed; the absolute
      bioavailability was 79%. The AUC of the R-NO metabolite generally exceeded that
      of ROF. After IV and PO administration, the metabolic ratios were 7.4 and 12.4,
      respectively. Dose-adjusted analysis of the R-NO AUC values indicate a 21% higher
      R-NO formation seen with PO vs. IV, suggesting entire first-pass conversion of
      ROF is to the active R-NO. Formation/clearance processes of the R-NO appear to be
      slow with an observed tmax of 6.9 - 8.8 h, and corresponding to apparent t1/2
      values of 22.7 h and 20.6 h, after IV and PO administration, respectively.
      CONCLUSION: ROF is rapidly absorbed after PO administration and exhibits high
      absolute bioavailability and low clearance pharmacokinetics. The total exposure
      of R-NO exceeds that of ROF by a factor of 12 after oral administration.

PMID- 21176728
TI  - The 8th annual meeting of CESAR in St. Gallen--novel therapeutic concepts in
      hemato-oncology.

PMID- 21176729
TI  - Cytotoxic effects of opioids on cancer cell lines.

PMID- 21176730
TI  - Integrating predictive biomarkers and classifiers into oncology clinical
      development programs: an adaptive, evidence-based approach.

PMID- 21176731
TI  - MRI Molecular imaging with albumin nanoparticles: achievements and challenges.

PMID- 21176732
TI  - Relevance of microRNA modulation in chemoresistant colon cancer in vitro.

PMID- 21176733
TI  - Suicide activation in a 5-fluorouracil resistant colon cancer model in vitro.

PMID- 21176734
TI  - Stable combretastatin A-4 analogues with sub-nanomolar efficacy against
      chemoresistant HT-29 cells.

PMID- 21176735
TI  - MRI molecular imaging with nanoparticles: a technical platform for early
      diagnosis of cancer.

PMID- 21176736
TI  - The impact of lysophosphatidylcholine (LPC) on the signaling pathways in melanoma
      cells. [corrected]

PMID- 21176737
TI  - Chemosensitivity of conjunctival melanoma cell lines to chemotherapeutic agents.

PMID- 21176738
TI  - Cross-resistance of 5-fluorouracil-resistant colon carcinoma in vitro.

PMID- 21176739
TI  - Measurement of 5-FU plasma levels in patients with advanced cancer: correct
      approach to practical procedures is essential.

PMID- 21176740
TI  - Comparison of seminal vesicle, non-malignant and malignant prostate tissues with
      gene expression patterns using quantitative real-time PCR.

PMID- 21176741
TI  - Biomarker response on exposure to sunitinib and its primary metabolite (SU12662)
      in metastatic colorectal cancer patients.

PMID- 21176742
TI  - Choice and simulation of the randomization procedure for clinical trials.

PMID- 21176743
TI  - Anti-inflammatory and anti-cancer activities of essential oils and their
      biological constituents.

PMID- 21176744
TI  - A preliminary report of a Phase II study of folinic acid, 5-fluorouracil,
      irinotecan (FOLFIRI) plus sunitinib with toxicity, efficacy, pharmacokinetics,
      biomarker, imaging data in patients with colorectal cancer with liver metastases
      as 1st line treatment.

PMID- 21176745
TI  - Difference in coronary artery intima and media calcification in autopsied
      patients with chronic kidney disease.
AB  - BACKGROUND: In patients with chronic kidney disease (CKD), coronary artery
      calcification occurs at two distinct sites in the vessel wall: the intima and the
      media. Arterial media calcification (AMC), a nonocclusive condition, affects
      hemodynamics differently compared to arterial intima calcification (AIC), which
      occurs in atherosclerotic plaques. Arterial calcification is considered a cell
      regulated process resembling intramembranous bone formation. The purpose of this
      retrospective observational study was to clarify the morphological differences
      between AIC and AMC and to evaluate the role of vascular smooth muscle cells
      (VSMCs) and macrophages in AIC and AMC formation. METHODS: We histologically
      analyzed 14 tissue specimens from 14 autopsies of patients with CKD Stage 5D who
      underwent hemodialysis and 5 specimens from 5 patients with CKD Stage 2 - 3 (90
      ml/min/1.73 m2 > estimated GFR >= 30 ml/min/1.73 m2). We performed
      immunohistochemical staining of osteopontin (OPN) as a marker for bone matrix
      protein, alpha-smooth muscle actin (alphaSMA) for VSMCs, Cbfa1/Runx2 as a marker
      for osteoblastic differentiation of VSMCs, and CD68 for macrophages. RESULTS: In
      the CKD 2/3 group, we also found AIC and AMC. OPN and CD68 expression in the CKD
      2/3 group was similar to that in the CKD 5D group. Although we did not find
      Cbfa1/Runx2 positive cell expression in the CKD 2/3 group, we did find it in the
      CKD 5D group. We found CD68-positive cells predominantly in AIC and absent in AMC
      in both groups. CONCLUSIONS: These findings suggest that the influence of
      Cbfa1/Runx2 pathway in coronary artery calcification depends on the CKD Stage.
      Expression of CD68-positive cells depends on the location of the coronary artery
      calcification.

PMID- 21176746
TI  - Sodium thiosulfate-based treatment in calcific uremic arteriolopathy: a
      consecutive case series.
AB  - BACKGROUND: Calcific uremic arteriolopathy (CUA) is a rare complication in end
      stage renal disease with high mortality. Numerous case reports and one case
      series of 3 patients report the benefit of sodium thiosulfate (STS) for treatment
      of CUA. The purpose of this evaluation was to examine the response to a STS-based
      treatment approach in patients with CUA with 1 year follow up. METHODS: A
      retrospective case series of 6 consecutive patients from Manitoba, Canada who met
      predefined diagnostic criteria for CUA and received STS between 2006 and 2008
      were included. STS responders were defined as improvement in at least one of the
      following three parameters: pain severity, wound size and diagnostic
      imaging/radiography. Mortality, STS dose, duration, adverse events and cost were
      also collected. RESULTS: Four patients were classified as responders. The 2
      responders who survived at 1 year of follow-up demonstrated an improvement in all
      3 parameters examined including an improvement in their follow-up diagnostic
      imaging results within the first 4 - 6 weeks of STS treatment. At 1 year of
      follow-up, 3 patients died. CONCLUSION: Using an STS-based multifaceted treatment
      approach for CUA, 4 patients responded but 3 of 6 patients died within 1 year.
      Further larger prospective studies are needed to delineate STS responders from
      non-responders.

PMID- 21176748
TI  - The role of adiponectin in metabolic and vascular disease: a review.
AB  - Adiponectin is a protein secreted by adipose tissue. Unlike other adipocytokines
      produced by adipose tissue, adiponectin appears to have anti-inflammatory, anti
      diabetic, and anti-atherogenic properties. Although secreted solely by adipose
      tissue, plasma levels of adiponectin are generally negatively related to total
      adipose mass; with higher plasma adiponectin levels in lean individuals and lower
      adiponectin levels in obese individuals. Plasma concentrations of adiponectin are
      lower in patients with insulin resistance compared to insulin sensitive patients;
      and lower in patients with diabetes compared to non-diabetics. A similar inverse
      relationship of plasma adiponectin level has been reported with hypertension
      (HTN), blood pressure level, and albuminuria. However, in chronic kidney disease
      (CKD) marked elevations in plasma adiponectin concentrations have been described.
      Plasma adiponectin levels are markedly elevated among patients with end-stage
      renal disease and are lower following kidney transplantation. Considering the
      inverse relationship of plasma adiponectin with renal function, the
      cardiovascular protective role of adiponectin in patients with CKD remains
      controversial. Further research on the distribution and function of different
      circulating fractions of adiponectin in patients with CKD will be needed in order
      to determine if adiponectin is a useful biomarker in patients with CKD.

PMID- 21176747
TI  - Impact of immunosuppressive therapy on hepatitis C infection after renal
      transplantation.
AB  - BACKGROUND: Among patients after renal transplantation (NTx), hepatitis C virus
      (HCV) infection is a risk factor for graft loss and patient death caused by
      hepatic decompensation. Also, HCV has been implicated in the pathogenesis of
      glomerular diseases in native and transplanted kidneys. Therefore, the aim of
      this retrospective cohort study was to determine the effects of the widely used
      calcineurin inhibitors (CNI) cyclosporine A (CsA) and tacrolimus (Tac) on
      hepatitis C virus replication, inflammatory activity, development of liver
      fibrosis, and long-term renal graft function. SUBJECTS AND METHODS: A cohort of
      71 patients with HCV infection after kidney transplantation under
      immunosuppression with either CsA or Tac were analyzed for viral kinetics and
      serum transaminases. In addition, presence of liver fibrosis was detected by non
      invasive measurements using the FibroScan. Graft function was determined
      biochemically. Patients with interferon therapy prior to transplantation were
      excluded from the study in order to avoid any impact of the antiviral therapy on
      outcomes. RESULTS: In the early period after transplantation, hepatitis C viral
      load was lower in patients treated with Tac as compared to CsA. This effect
      became negligible 3 months after transplantation. However, hepatic inflammatory
      activity was reduced in the CsA-treated group. Extent of liver fibrosis was
      similar in both groups of HCV-infected patients as well as in a control group of
      non-HCV-infected patients after renal transplantation (NTx), respectively. Renal
      function and glomerular filtration rate, as calculated by the modification of
      diet in renal disease (MDRD) formula, were significantly better in patients
      treated with Tac. CONCLUSIONS: During long-term immunosuppression, the CNIs
      cyclosporine A versus tacrolimus showed no significant differences in HCV
      infected patients after renal transplantation with respect to viral replication
      and development of liver fibrosis. However, function of the renal graft is
      significantly better preserved in patients receiving tacrolimus.

PMID- 21176749
TI  - Fifty years of Balkan endemic nephropathy in Romania: some aspects of the endemic
      focus in the Mehedinti county.
AB  - Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial nephritis seen
      primarily in countries in the Balkan Peninsula. The disease, which was first
      described in Romania 50 years ago, often manifests as a form of chronic nephritis
      that is also associated with upper urothelial cancers (UUC). This review
      summarizes the observations and studies performed in Romania regarding this
      disease during the last 50 years with particular emphasis on Mehedinti county.
      The paper analyzes current data on the epidemiology of the disease in this area,
      specifically in relation to the observations made in dialysis centers in the same
      area. It also discusses the diagnostic criteria of patients with BEN stemming
      from collaborations between specialists working in other countries affected by
      the disease. Moreover, the paper analyzes the main etiological factors suspected
      to play a role in BEN: aristolochic acid (the disease has many similarities to
      aristolochic nephropathy caused by Chinese herbs), mycotoxins, toxic substances
      from pliocene lignite, genetic factors, and viruses. Studies performed by
      Romanian authors are presented briefly in comparison to studies performed by
      other authors. Finally, given that BEN is an important health problem in the
      region, the relationship between BEN and UUC is further analyzed.

PMID- 21176751
TI  - Biosimilar epoetin zeta in nephrology - a single-dialysis center experience.
AB  - AIM: An observational clinical study was performed to test the efficiency of the
      biosimilar product epoetin zeta to maintain stable hemoglobin levels in end-stage
      renal disease (ESRD) patients on intermittent high-flux hemodialysis. PATIENTS
      AND METHODS: Before the start of the study, 17 out of 18 patients were on various
      erythropoiesis-stimulating agents (ESA). After a run-in period of 2 months, all
      patients switched to epoetin zeta and were followed for 6 months. The initial
      weekly doses as well as the frequency of application per week were kept constant.
      To convert patients on darbepoetin (n = 12) to epoetin zeta, a factor of 1 : 200
      was used. During the follow-up, hemoglobin levels, iron status, dialysis
      efficiency, body weight, and adverse events were monitored at least once a month.
      RESULTS: Comparing time 0 (before the start of epoetin zeta) with the end of the
      study (6 months of epoetin zeta), no significant changes were observed:
      Hemoglobin 11.72 +/- 0.64 g/dl versus 11.62 +/- 0.70 g/dl (p = 0.64); weekly dose
      of ESA: 79.4 +/- 57.7 IU/kg/week at start versus 91.8 +/- 65.4 IU/kg/week at the
      end (p = 0.55). It is noteworthy that the frequency of application could be
      reduced to once a week or less with epoetin zeta in 66% of the 18 patients. After
      6 months of epoetin zeta, 10 patients received 1 dose/week, and 2 patients
      received only 1 dose every 2 weeks. There were no significant changes in mean
      blood pressure, body weight and hemodialysis efficiency comparing the end with
      the start of the observation. No side effects attributable to the ESA-therapy
      have been observed. CONCLUSION: The biosimilar product epoetin zeta is safe in
      clinical practice and is effective and stable in the weekly dose as well as in
      the frequency of application. Biosimilars offer a welcome opportunity to reduce
      treatment costs of renal anemia.

PMID- 21176750
TI  - Relationship between insulin resistance and erythropoietin responsiveness in
      hemodialysis patients.
AB  - BACKGROUND: Insulin resistance is an independent predictor of cardiovascular
      mortality in hemodialysis (HD) patients. Inflammation plays an important role in
      insulin resistance, and adipocytokines, including tumor necrosis factor-alpha and
      leptin, can induce insulin resistance. However, data on insulin resistance and
      erythropoietin responsiveness in HD patients are lacking. METHODS: We conducted a
      prospective, observational cohort study to clarify the relationship between
      insulin resistance and erythropoietin responsiveness in HD patients. Insulin
      resistance as assessed by the homeostasis model assessment for insulin resistance
      (HOMA-IR), levels of adiponectin and inflammatory cytokines, required
      erythropoietin (EPO) dose, and other metabolic parameters were measured in
      patients with (n = 52) and without diabetes (n = 55) over the course of 12
      months. RESULTS: The diabetes group had significantly higher serum leptin, high
      sensitivity C-reactive protein, and interleukin-6 concentrations but lower serum
      adiponectin concentration. Average hemoglobin (Hb) levels during the 12-month
      study period were significantly lower in the diabetes group than in the non
      diabetes group, and a higher dose of EPO was required in the diabetes group.
      There was a significant negative correlation between adiponectin and HOMA-IR, a
      significant positive correlation between EPO dose and HOMA-IR, and a significant
      negative correlation between EPO dose and adiponectin in the two groups. Insulin
      resistance as established by HOMA-IR and adiponectin was associated with EPO
      responsiveness in HD patients. HOMA-IR, Hb, and adiponectin levels were found to
      be independent predictors of EPO dose in HD patients with diabetes. CONCLUSION:
      Insulin resistance is associated with EPO responsiveness in HD patients. Patients
      in the diabetes group had a lower response to EPO than those in the non-diabetes
      group. For improvement in EPO response, insulin resistance may be a new target
      for treating HD patients.

PMID- 21176752
TI  - Pharmacokinetics and safety of multiple doses of daptomycin 6 mg/kg in
      noninfected adults undergoing hemodialysis or continuous ambulatory peritoneal
      dialysis.
AB  - AIMS: The purpose of this study was to characterize the pharmacokinetics and
      tolerability of daptomycin in subjects undergoing hemodialysis (HD) or continuous
      ambulatory peritoneal dialysis (CAPD). METHOD: 16 noninfected adults on stable
      dialysis regimens were enrolled. Daptomycin 6 mg/kg was administered after HD
      during a 48 h - 48 h - 72 h dialysis week or before a CAPD dwell time over a 48 h
      - 48 h - 48 h dialysis week. Pharmacokinetic parameters were described, and
      adverse events were monitored. RESULTS: Daptomycin had mean half-lives in HD
      subjects of 28.0 and 35.9 h on Days 1 and 5, with corresponding values of 25.8
      and 26.7 h in CAPD subjects. Steady state was reached by Day 5 in both groups. At
      steady state, HD subjects had a mean peak plasma concentration (Cmax) of 81.6
      ug/ml and a mean trough concentration of 15.3 ug/ml (on Day 8). In CAPD subjects,
      Cmax was 93.9 ug/ml and the trough was 20.7 ug/ml (on Day 7). Adverse events were
      experienced by 71.4% and 66.7% of HD and CAPD subjects, respectively. Most of
      these were mild or moderate in intensity; however, 2 subjects experienced muscle
      spasms and mild creatine phosphokinase elevations although neither event was
      considered to be related to study drug. CONCLUSIONS: The pharmacokinetics of
      daptomycin 6 mg/kg support a dosing regimen of every 48 h in CAPD and thrice
      weekly dosing in HD.

PMID- 21176753
TI  - Unsuccessful application of taurolidine in the treatment of fungal peritonitis in
      peritoneal dialysis.
AB  - Fungal peritonitis (FP) is a serious complication for peritoneal dialysis (PD)
      patients, determining hospitalization, technique failure, catheter loss and
      death. In the 2005 update, treatment recommendations for FP from the
      International Society of Peritoneal Dialysis (ISPD) advocate catheter removal
      immediately after fungi are identified by microscopy or culture. The availability
      of more effective medical treatments could therefore be of great importance. The
      aim of this report is to describe a case of a 43-year-old, diabetic, HIV positive
      PD patient with fluconazole resistant Candida peritonitis, who was treated with
      an i.p. taurolidine solution. Taurolidine is a non-antibiotic antimicrobial, with
      broad bactericidal and fungicidal properties. It has been used during surgery for
      lavage of the peritoneum in cases of peritonitis. Its mechanism of action is
      related to direct toxic action on micro-organisms, through a chemical reaction
      between active taurolidine derivatives and structures on the cell wall. Treatment
      failed because the patient had severe burning pain during i.p. administration of
      the drug, limiting its dose. PD catheter removal allowed complete recovery. It
      remains undetermined if, with different doses and methodology, taurolidine could
      be more effective in treating bacterial and/or fungal peritonitis. Currently,
      catheter removal remains the most effective therapy of fungal peritonitis.

PMID- 21176754
TI  - Systemic non-amyloidotic fibril deposition disease: a probable variant form of
      fibrillary glomerulonephritis.
AB  - Fibrillary glomerulonephritis (FGN) is characterized by deposition of non
      amyloidotic fibrillary material in glomeruli, and most patients with the disease
      show heavy proteinuria and hematuria, and progress into end-stage renal failure.
      We report a 62-year-old woman with FGN who showed mild proteinuria without
      hematuria and developed rapidly progressive renal failure requiring hemodialysis.
      Renal biopsy showed severe tubulointerstitial injury associated with non
      amyloidotic fibrillary deposits in the tubular basement membrane, interstitium
      and vessel walls, in addition to glomeruli. The patient died from liver abscess 1
      year after the introduction of hemodialysis. Postmortem examination showed the
      presence of non-amyloidotic fibrillary deposits arranged in tightly packed
      electron-dense and bundle-shaped structures in many organs. These findings
      suggest systemic non-amyloidotic fibril deposition in FGN.

PMID- 21176755
TI  - An uncommon glomerular disease in an HIV patient: value of renal biopsy and
      review of the literature.
AB  - Renal disease is not uncommon in those infected with HIV. The most common
      manifestation of HIV in the kidney is HIV-associated nephropathy (HIVAN). Other
      HIV- and non-HIV-related causes have been described in the literature.
      Immunotactoid glomerulonephritis (ITG) is a rare disorder found in 0.06% of renal
      biopsies characterized by organized tubular immune complex deposits, observed
      more often in Caucasians. ITG tends to occur in an older age group and in some
      patients has been associated with a hemopoietic malignancy. In this report, we
      describe a case of ITG occurring in an HIV-positive, hepatitis C (HCV)- and
      hepatitis B (HBV)-negative female, who presented with microscopic hematuria and
      proteinuria. A percutaneous kidney biopsy showed diffuse membranous
      glomerulopathy, with mild mesangial proliferation and segmental sclerosing
      lesions containing mainly IgG, Kappa- and C3-positive deposits. Electron
      microscopy revealed diffuse subepithelial tubular deposits diagnostic of ITG. Out
      of 5 reported HIV-positive cases and ITG in the literature, 3 were HCV+, 2 were
      Caucasian and 3 were African-American (AA) without detectable hematologic
      malignancy. We report another case of ITG in an HCV- and HBV-negative, AA female.

PMID- 21176756
TI  - Acute pancreatitis in a 2-year-old girl on peritoneal dialysis and using
      icodextrin solution.

PMID- 21176757
TI  - [A system of prescriptions without drug approval: example of baclofen].
AB  - Baclofen is an anti-spastic drug that acts as an agonist of GABA-B receptors. It
      also seems to decrease the appetence for alcohol (anti-craving effect), although
      this effect has not been certified by Authorities for drug approval in France
      (AMM). However, baclofen receives a great deal of demand by patients hoping to
      reduce their alcohol consumption. Nonetheless, the lack of AMM and the high doses
      of baclofen supposed to exert an anti-craving effect often discourage
      practitioners from prescribing this drug in current medical practice. Therefore,
      it is preferable for a drug like baclofen to be prescribed under specific
      regulations. As such, certain criteria similar to those required in clinical
      trials are necessary to protect patients as well as the prescribing doctors. The
      criteria that are proposed here are: the use of drugs without AMM approval as a
      last resort (all other treatments must have failed), the collegiate decision for
      the drug prescription, good knowledge of the potency of the drug as well as good
      record keeping of patients and proper supervision. The departments of addiction,
      pharmacology and pharmacovigilance of the University Hospital of Lille, France
      present here a medical process named "multidisciplinary consultations for resort
      treatments of addictions" (CAMTEA). This process is designed to meet all the
      above mentioned criteria and to allow the use of baclofen as an anti-craving drug
      in safest conditions. If this proves to be successful with baclofen, it is
      possible to extend the use of CAMTEA to other drugs without AMM approval in
      addictologic pathologies.

PMID- 21176758
TI  - [Mephedrone: a designer drug of recent use in France].
AB  - Designer drugs are currently marketed as substitutes for stimulant drugs as
      cocaine, amphetamine, MDMA...Unlike compounds listed as narcotics, these new
      substances are deliberately synthesized to avoid anti-drug laws. Among them,
      mephedrone (4-methylmethcatinone) that belongs to cathinone family, has been
      recently introduced in France. Users report positive euphoric and entactogenic
      effects. They also describe negative effects such as increased dependence towards
      the drug itself and larger craving for tobacco and alcohol. The numerous and
      various described adverse effects include psychoactive, digestive,
      cardiovascular... effects. Some fatality cases have been reported in scientific
      literature or in press and attributed to mephedrone often in association with
      other substances. Mephedrone has been listed as narcotic in several European
      countries and more recently in France.

PMID- 21176759
TI  - [Drugs administration by subcutaneous injection within palliative care].
AB  - Drugs delivery by subcutaneous injection is often the last resort/appeal for a
      doctor anxious to limit the aggressive and invasive treatments, particularly
      within palliative care. A review was made to list the drugs which can be
      administered by this route. Concerned antibiotics are teicoplanin, netilmicin and
      gentamicin with a risk of skin necrosis for aminoglycosids. Midazolam is useful
      in various indications and can be associated with morphine in case of dyspnoea.
      Data about subcutaneous injection of dexamethasone, clonazepam, haloperidol and
      levomepromazine are published; it is the same for fentanyl, nefopam, ondansetron
      and metoclopramide. The subcutaneous injection of these quoted drugs is possible,
      but requires further studies.

PMID- 21176760
TI  - Safety review: squalene and thimerosal in vaccines.
AB  - Few studies show the reluctance of the people to get vaccinated against A (H1N1)
      influenza for fear of side effects of squalene (MF59, AS03, AF03) and thimerosal.
      The aim of this paper is to assess the safety in using these adjuvants and
      preservative reviewing data of clinical trials relative to which formulation
      includes these compounds. In the current state of knowledge, these vaccines have
      proved to be effective even though they more frequently give local adverse events
      than non-adjuvanted influenza vaccines. Systemic side effects are generally not
      serious. In the studies, adjuvanted vaccines do not increase neither the risk of
      Guillain Barre syndrome nor auto-immune diseases. There is no convincing evidence
      that exposure to thimerosal in vaccines had any deletorious effect on
      physiological outcome.

PMID- 21176761
TI  - [DRESS syndrome: 11 case reports and a literature review].
AB  - AIM: Study the epidemiological, clinical, biological and chronological drug rash
      with eosinophilia and systemic symptoms (DRESS) characteristic and indicate the
      implicated drugs. METHODS: We carried a retrospective study including all DRESS
      cases notified to the Pharmacovigilance Unit of Monastir. RESULTS: Our cohort of
      eleven patients had a median age of 40 years. Clinical examination revealed skin
      eruption and fever among all patients. Laboratory findings showed marked
      eosinophilia among all patients, hepatic cytolysis among eight patients and
      creatinin serum level increase among four patients. An interstitial pulmonary
      syndrome was noted among two patients. After culprit-drug withdrawal, outcomes
      were favorable for all patients. Skin tests were positive with carbamazepin and
      cefotaxim and negative with sulfasalazine, allopurinol and terbinafine.
      CONCLUSION: Throughout this paper, we point out the contribution of skin tests to
      identify implicated drug in inducing DRESS and to testify cross reactivity and we
      point out the possibility of neosensitisation to a non related chemical drug
      after DRESS syndrome.

PMID- 21176762
TI  - [Ethical quality of nursing care in Lebanon].
AB  - OBJECTIVE: The objective was to reflect on the nurse's role and on the
      determinants of a responsible choice. In order to do it, we tried to answer the
      following questions: (1) Are the role and the mission of the nursing body well
      acquired in Lebanon? (2) Are there international and national norms which govern
      the accomplishment of this mission? (3) At what point does the mission
      accomplished by the nursing body procure the patient's safety? (4) What are the
      factors that modify the performance of the nursing body in Lebanon? And, (5) What
      are the challenges of a good-quality nursing performance? METHODS: We conducted a
      double arm survey. The first one is made on 160 nurses working in 19 hospitals
      that succeeded to establish until July 2008 (end of study) at least an ethical
      committee for medical care. The second one was conducted on the heads of the
      nursing departments in 49 private institutes, 34 public institutes and 16
      universities. RESULTS AND DISCUSSION: The investigated nurses don't know very
      well the medical and nursing ethics' principles that are very well highlighted in
      the Husted decisional model and expressed by justice, autonomy, confidentiality,
      beneficience, veracity and fidelity. This result underlines a fact that affects
      the nurse's mission and so on the patients' safety. Ninety-four per cent of the
      nurses think that the education and the communication with the patient is not a
      priority during their daily work, which hinders the three essential times
      (analysis, communication and assessment) required to elaborate a freely informed
      decision. Ethics don't have a solid basis in education. CONCLUSION: We must be
      concerned by this diagnostic, but it leads to the hope of being able to find
      together, through a common reflection, the essential characteristics to assume
      our responsibilities whether in the medical or nursing domain.

PMID- 21176763
TI  - Bleedings induced by oral anticoagulants: a study of adverse drug reactions
      reported to Midi-Pyrenees PharmacoVigilance Centre between 2003 and 2006.

PMID- 21176764
TI  - Monitoring of a baby with neonatal hypothyroidism after maternal exposure to
      propylthiouracil.

PMID- 21176765
TI  - [Qualitative evaluation of drug prescription by phone at the call center 15: a
      pilot study].

PMID- 21176766
TI  - [Benefit of early prescription of Risperdal RLAI: a study of 25 psychotic
      patients hospitalised for the first time in their district service].

PMID- 21176767
TI  - [A chronic gingival hypertrophy].

PMID- 21176768
TI  - Tyrosine hydroxylase and regulation of dopamine synthesis.
AB  - Tyrosine hydroxylase is the rate-limiting enzyme of catecholamine biosynthesis;
      it uses tetrahydrobiopterin and molecular oxygen to convert tyrosine to DOPA. Its
      amino terminal 150 amino acids comprise a domain whose structure is involved in
      regulating the enzyme's activity. Modes of regulation include phosphorylation by
      multiple kinases at four different serine residues, and dephosphorylation by two
      phosphatases. The enzyme is inhibited in feedback fashion by the catecholamine
      neurotransmitters. Dopamine binds to TyrH competitively with tetrahydrobiopterin,
      and interacts with the R domain. TyrH activity is modulated by protein-protein
      interactions with enzymes in the same pathway or the tetrahydrobiopterin pathway,
      structural proteins considered to be chaperones that mediate the neuron's
      oxidative state, and the protein that transfers dopamine into secretory vesicles.
      TyrH is modified in the presence of NO, resulting in nitration of tyrosine
      residues and the glutathionylation of cysteine residues.

PMID- 21176771
TI  - A variant of arrestin-1 binds rod outer segment membranes in a light-independent
      manner.
AB  - A 50-kDa-polypeptide band peripherally bound to retinal rod outer segment (ROS)
      membranes was purified by anion-exchange chromatography. When the 50-kDa protein
      was compared with purified arrestin-1, it was observed that: (1) both proteins
      comigrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and were
      recognized by either anti-50-kDa protein polyclonal antibodies or anti-arrestin-1
      monoclonal antibodies; (2) protein fragments and peptide fingerprint maps
      obtained following limited and complete proteolysis with specific proteases were
      very similar for both molecules; and (3) several chromatographically-purified
      tryptic peptides from the 50-kDa protein possessed the same amino acid
      composition as tryptic peptides deduced from the reported arrestin-1 primary
      structure. Consequently, arrestin-1 and the purified 50-kDa protein must
      correspond to variants of the same molecule. However, in contrast to arrestin-1
      that associated to the ROS membranes only in the presence of light and ATP, the
      50-kDa protein interacted with the ROS membranes in a light-independent manner,
      either in the presence or absence of ATP. These results clearly established that
      phosphorylated and illuminated rhodopsin is not the membrane anchor for this
      variant of arrestin-1.

PMID- 21176770
TI  - 1,25-Dihydroxyvitamin D3 suppresses inflammation-induced expression of
      plasminogen activator inhibitor-1 by blocking nuclear factor-kappaB activation.
AB  - Plasminogen activator inhibitor (PAI)-1 is a major fibrinolytic inhibitor. High
      PAI-1 is associated with increased renal and cardiovascular disease risk.
      Previous studies demonstrated PAI-1 down-regulation by 1,25-dihydroxyvitamin D3
      (1,25(OH)2D3), but the molecular mechanism remains unknown. Here we show that
      exposure of mouse embryonic fibroblasts to TNFalpha or LPS led to a marked
      induction of PAI-1, which was blunted by 1,25(OH)2D3, NF-kappaB inhibitor or p65
      siRNA, suggesting the involvement of NF-kappaB in 1,25(OH)2D3-induced repression.
      In mouse Pai-1 promoter a putative cis-kappaB element was identified at -299.
      EMSA and ChIP assays showed that TNF-alpha increased p50/p65 binding to this
      kappaB site, which was disrupted by 1,25(OH)2D3. Luciferase reporter assays
      showed that PAI-1 promoter activity was induced by TNFalpha or LPS, and the
      induction was blocked by 1,25(OH)2D3. Mutation of the kappaB site blunted
      TNFalpha, LPS or 1,25(OH)2D3 effects. 1,25(OH)2D3 blocked IkappaBalpha
      degradation and arrested p50/p65 nuclear translocation. In mice LPS stimulated
      PAI-1 expression in the heart and macrophages, and the stimulation was blunted by
      pre-treatment with a vitamin D analog. Together these data demonstrate that
      1,25(OH)2D3 down-regulates PAI-1 by blocking NF-kappaB activation. Inhibition of
      PAI-1 production may contribute to the reno- and cardio-protective effects of
      vitamin D.

PMID- 21176772
TI  - High-throughput cryopreservation of spermatozoa of blue catfish (Ictalurus
      furcatus): Establishment of an approach for commercial-scale processing.
AB  - Hybrid catfish created by crossing of female channel catfish (Ictalurus
      punctatus) and male blue catfish (Ictalurus furcatus) are being used increasingly
      in foodfish aquaculture because of their fast growth and efficient food
      conversion. However, the availability of blue catfish males is limited, and their
      peak spawning is at a different time than that of the channel catfish. As such,
      cryopreservation of sperm of blue catfish could improve production of hybrid
      catfish, and has been studied in the laboratory and tested for feasibility in a
      commercial dairy bull cryopreservation facility. However, an approach for
      commercially relevant production of cryopreserved blue catfish sperm is still
      needed. The goal of this study was to develop practical approaches for commercial
      scale sperm cryopreservation of blue catfish by use of an automated high
      throughput system (MAPI, CryoBioSystem Co.). The objectives were to: (1) refine
      cooling rate and cryoprotectant concentration, and evaluate their interactions;
      (2) evaluate the effect of sperm concentration on cryopreservation; (3) refine
      cryoprotectant concentration based on the highest effective sperm concentration;
      (4) compare the effect of thawing samples at 20 or 40 degrees C; (5) evaluate the
      fertility of thawed sperm at a research scale by fertilizing with channel catfish
      eggs; (6) test the post-thaw motility and fertility of sperm from individual
      males in a commercial setting, and (7) test for correlation of cryopreservation
      results with biological indices used for male evaluation. The optimal cooling
      rate was 5 degrees C/min (Micro Digitcool, IMV) for high-throughput
      cryopreservation using CBS high-biosecurity 0.5-ml straws with 10% methanol, and
      a concentration of 1*10(9)sperm/ml. There was no difference in post-thaw motility
      when samples were thawed at 20 degrees C for 40s or 40 degrees C for 20s. After
      fertilization, the percentage of neurulation (Stage V embryos) was 80+/-21%, and
      percentage of embryonic mobility (Stage VI embryo) was 51+/-22%. There was a
      significant difference among the neurulation values produced by thawed blue
      catfish sperm, fresh blue catfish sperm (P=0.010) and channel catfish sperm
      (P=0.023), but not for Stage VI embryos (P>=0.585). Cryopreserved sperm from ten
      males did not show significant variation in post-thaw motility or fertility at
      the neurulation stage. This study demonstrates that the protocol established for
      high-throughput cryopreservation of blue catfish sperm can provide commercially
      relevant quantities and quality of sperm with stable fertility for hybrid catfish
      production and provides a model for establishment of commercial-scale approaches
      for other aquatic species.

PMID- 21176773
TI  - Expression of Toll-like receptors and antimicrobial peptides during Eimeria
      praecox infection in chickens.
AB  - Intestinal colonization of avian species by Eimeria parasites results in the
      enteric disease, coccidiosis. A study was carried out to assess the immunologic
      effects of Eimeria praecox infection on the gut of infected chickens. In
      Experiment 1, birds were orally gavaged with 50,000 E. praecox oocysts; in
      Experiment 2, an infection dosage of 500,000 E. praecox oocysts was used.
      Duodenal and jejunal intestinal sections were sampled consecutively on days 1-7
      post-infection. Intestinal expression of innate immune gene transcripts was
      analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Analysis
      of relative gene expression in Experiment 1 revealed an increase (P<0.05) in
      duodenal Toll-like receptor (TLR)3 expression on days 4 and 6 post-infection.
      TLR15 expression was significantly decreased in the duodenum of infected birds on
      day 2, and significantly increased on day 6 post-infection. In Experiment 2, TLR3
      was significantly downregulated in the duodenum on day 7 post-infection; however,
      no significant results were observed in terms of TLR15 expression. TLR4 also
      exhibited decreased expression (P<0.05) on day 7 post-infection in both
      intestinal sections. Regarding antimicrobial peptide expression; in the first
      experiment, expression of liver-expressed antimicrobial peptide-2 (LEAP-2) in
      infected birds was significantly decreased in the duodenum on days 3 and 4, and
      in the jejunum on day 4. Similarly, Experiment 2 resulted in depression of LEAP-2
      (P<0.05) on days 3-5 in the duodenum. In Experiment 1, cathelicidin antimicrobial
      peptide (CATHL3) was downregulated (P<0.05) in the jejunum of infected chickens
      on day 3 post-infection; however, CATHL3 results were non-significant in
      Experiment 2. Based on the differing results observed in each experiment, it was
      concluded that both TLR and antimicrobial peptide expression, and thus immunity
      may be dependent on infection load.

PMID- 21176769
TI  - Keratin gene mutations in disorders of human skin and its appendages.
AB  - Keratins, the major structural protein of all epithelia are a diverse group of
      cytoskeletal scaffolding proteins that form intermediate filament networks,
      providing structural support to keratinocytes that maintain the integrity of the
      skin. Expression of keratin genes is usually regulated by differentiation of the
      epidermal cells within the stratifying squamous epithelium. Amongst the 54 known
      functional keratin genes in humans, about 22 different genes including, the
      cornea, hair and hair follicle-specific keratins have been implicated in a wide
      range of hereditary diseases. The exact phenotype of each disease usually
      reflects the spatial expression level and the types of mutated keratin genes, the
      location of the mutations and their consequences at sub-cellular levels as well
      as other epigenetic and/or environmental factors. The identification of specific
      pathogenic mutations in keratin disorders formed the basis of our understanding
      that led to re-classification, improved diagnosis with prognostic implications,
      prenatal testing and genetic counseling in severe keratin genodermatoses.
      Molecular defects in cutaneous keratin genes encoding for keratin intermediate
      filaments (KIFs) causes keratinocytes and tissue-specific fragility, accounting
      for a large number of genetic disorders in human skin and its appendages. These
      diseases are characterized by keratinocytes fragility (cytolysis), intra
      epidermal blistering, hyperkeratosis, and keratin filament aggregation in
      severely affected tissues. Examples include epidermolysis bullosa simplex (EBS;
      K5, K14), keratinopathic ichthyosis (KPI; K1, K2, K10) i.e. epidermolytic
      ichthyosis (EI; K1, K10) and ichthyosis bullosa of Siemens (IBS; K2),
      pachyonychia congenita (PC; K6a, K6b, K16, K17), epidermolytic palmo-plantar
      keratoderma (EPPK; K9, (K1)), monilethrix (K81, K83, K86), ectodermal dysplasia
      (ED; K85) and steatocystoma multiplex. These keratins also have been identified
      to have roles in apoptosis, cell proliferation, wound healing, tissue polarity
      and remodeling. This review summarizes and discusses the clinical,
      ultrastructural, molecular genetics and biochemical characteristics of a broad
      spectrum of keratin-related genodermatoses, with special clinical emphasis on
      EBS, EI and PC. We also highlight current and emerging model tools for prognostic
      future therapies. Hopefully, disease modeling and in-depth understanding of the
      molecular pathogenesis of the diseases may lead to the development of novel
      therapies for several hereditary cutaneous diseases.

PMID- 21176774
TI  - Effects of carotenoids, immune activation and immune suppression on the intensity
      of chronic coccidiosis in greenfinches.
AB  - Allocation trade-offs of carotenoids between their use in the immune system and
      production of integumentary colouration have been suggested as a proximate
      mechanism maintaining honesty of signal traits. We tested how dietary carotenoid
      supplementation, immune activation and immune suppression affect intensity of
      coccidian infection in captive greenfinches Carduelis chloris, a passerine with
      carotenoid-based plumage. Immune activation with phytohaemagglutinin (PHA)
      decreased body mass among birds not supplemented with lutein, while among the
      carotenoid-fed birds, PHA had no effect on mass dynamics. Immune suppression with
      dexamethasone (DEX) induced loss of body mass and reduced the swelling response
      to PHA. DEX and PHA increased the concentration of circulating heterophils.
      Lutein supplementation increased plasma carotenoid levels but had no effect on
      the swelling response induced by PHA. PHA and DEX treatments did not affect
      plasma carotenoids. Immune stimulation by PHA suppressed the infection, but only
      among carotenoid-supplemented birds. Priming of the immune system can thus aid in
      suppressing chronic infection but only when sufficient amount of carotenoids is
      available. Our experiment shows the importance of carotenoids in immune response,
      but also the complicated nature of this impact, which could be the reason for
      inconsistent results in studies investigating the immunomodulatory effects of
      carotenoids. The findings about involvement of carotenoids in modulation of an
      immune response against coccidiosis suggest that carotenoid-based ornaments may
      honestly signal individuals' ability to manage chronic infections.

PMID- 21176775
TI  - Influence of long-term treatment with pravastatin on the survival, evolution of
      cutaneous lesion and weight of animals infected by Leishmania amazonensis.
AB  - The high toxicity of current drugs for treatment of leishmaniasis is a major
      hindrance for controlling the disease. Pravastatin is a well-known drug with anti
      inflammatory and immunomodulatory properties that may modulate host defense
      mechanisms against Leishmania. We evaluated the influence of prolonged
      pravastatin treatment on the survival of Leishmania amazonensis-infected animals
      (BALB/c, C57BL6 mice and Syrian hamsters), including weekly measurement of
      cutaneous lesions (footpad thickness) and weight. Pravastatin improved survival
      of Leishmania-infected BALB/c mice but not of infected C57BL6 mice or hamsters.
      On the 50th week of follow-up, 71% of pravastatin-treated Leishmania-infected
      BALB/c mice were alive against 29% of control group (p<0.01). Low footpad
      thickness was found on BALB/c pravastatin treated mice from the 14th week
      (p<0.05), and 20th week onward for C57BL6 treated mice. Pravastatin treatment
      decreased weight loss in Leishmania-infected C57BL6 mice and Syrian hamsters, but
      not infected BALB/c mice. Our results points to beneficial effects of pravastatin
      on the evolution of the disease in the murine leishmaniasis model.

PMID- 21176776
TI  - PU.1 directly regulates retinoic acid-induced expression of RIG-G in leukemia
      cells.
AB  - RIG-G is a retinoic acid- or interferon-induced gene with potential anti
      proliferation function. However, the mechanism underlying ATRA-induced RIG-G
      induction is not completely understood. Here, we demonstrate that ATRA up
      regulates the expression of PU.1, which in turn directly binds to the promoter
      and increases the expression of RIG-G gene. Luciferase reporter assay and
      electrophoretic mobility shift assay reveal that PU.1 preferentially binds to one
      of the two putative binding sites on the RIG-G promoter. Moreover, silencing of
      PU.1 by shRNA markedly inhibited ATRA- but not IFNalpha-induced expression of RIG
      G. These data provide new insight into the mechanism of ATRA-induced RIG-G
      expression.

PMID- 21176777
TI  - Up-regulation of the vitamin C transporter SVCT2 upon differentiation and
      depolarization of myotubes.
AB  - In addition to its role as a strong antioxidant, vitamin C regulates the
      differentiation of several cell lineages. In vertebrate skeletal muscle, the
      vitamin C transporter SVCT2 is preferentially expressed in slow muscle fibers. To
      gain insights into the possible involvement of intracellular vitamin C on early
      myogenesis, we investigated the regulation of SVCT2 expression in cultures of
      chick fetal myoblasts. SVCT2 expression increases in cultures of both, slow and
      fast muscle-derived myoblasts, as they fuse to form mainly fast myotubes.
      Interestingly, we found that SVCT2 could be positively modulated by potassium
      induced depolarization of myotubes. These findings suggest that SVCT2-mediated
      uptake of vitamin C could play diverse roles on skeletal muscle development and
      physiology.

PMID- 21176778
TI  - Protein kinase C isoforms: mediators of reactive lipid metabolites in the
      development of insulin resistance.
AB  - The role of protein kinase C (PKCs) isoforms in the regulation of glucose
      metabolism by insulin is complex, partly due to the large PKC family consisting
      of three sub-groups: conventional, novel and atypical. Activation of some
      conventional and novel PKCs in response to increased levels of diacylglycerol
      (DAG) have been shown to counteract insulin signalling. However, roles of
      atypical PKCs (aPKCs) remain poorly understood. aPKCs act as molecular switches
      by promoting or suppressing signalling pathways, in response to insulin or
      ceramides respectively. Understanding how DAG- and ceramide-activated PKCs impair
      insulin signalling would help to develop treatments to fight insulin resistance.

PMID- 21176779
TI  - Polyglutamine shows a urea-like affinity for unfolded cytosolic protein.
AB  - Noting that the glutamine (Q) amino acid side-chain bears a striking resemblance
      to urea, the chemical denaturant, we argue on biophysical grounds that polyQ
      chains should possess a potent denaturant activity. Using live-cell confocal
      microscopy, we demonstrate that the surface of a polyQ inclusion denatures
      cytosolic proteins by binding and trapping them in an immobilized ring. We also
      show the reverse effect: that elevated local concentrations of unfolded protein
      in the cytosol can drive the co-localization and accumulation of short polyQ
      tracts that normally do not aggregate. Such a urea-like mechanism explains many
      past observations about polyQ-driven disruption of proteostasis and
      neurodegeneration.

PMID- 21176780
TI  - Localisation of the neuropeptide PACAP and its receptors in the rat parathyroid
      and thyroid glands.
AB  - PACAP (pituitary adenylate cyclase activating polypeptide) is widely distributed
      neuropeptide acting via three subtypes of receptors, PAC(1), VPAC(1) and VPAC(2).
      Here we examined the localisation and nature of PACAP-immunoreactive nerves in
      the rat thyroid and parathyroid glands and defined the distribution of PAC(1),
      VPAC(1) and VPAC(2) receptor mRNA's. In the parathyroid gland a large number of
      nerve fibres displaying PACAP-immunoreactivity were distributed beneath the
      capsule, around blood vessels and close to glandular cells. Most of the PACAP
      nerves were sensory, since they co-stored CGRP (calcitonin-gene-related peptide)
      and were sensitive to capsaicin-treatment. mRNA's for PAC(1) and VPAC(2)
      receptors occurred in the parathyroid gland, mainly located in the glandular
      cells. In the thyroid gland PACAP-immunoreactive nerve fibres were associated
      with blood vessels, thyroid follicles and parafollicular C-cells. A high degree
      of co-existence between PACAP and VIP (vasoactive intestinal polypeptide) was
      observed in the intrathyroid nerve fibres and cell bodies of the thyroid ganglion
      indicating a common origin for the two peptides. A minor population of PACAP
      immunoreactive nerve fibres with relation to blood vessels co-stored NPY
      (neuropeptide Y), whereas only a few fibres co-stored CGRP. PAC(1) and VPAC(1)
      receptor mRNA's occurred in follicular cells and blood vessels, whereas the
      expression of the VPAC(2) receptor was low. The findings suggest that PACAP plays
      a role in the regulation of parathyroid and thyroid blood flow and hormone
      secretion.

PMID- 21176781
TI  - Multi-locus analysis of Giardia duodenalis intra-Assemblage B substitution
      patterns in cloned culture isolates suggests sub-Assemblage B analyses will
      require multi-locus genotyping with conserved and variable genes.
AB  - Recent research concerning Giardia duodenalis has focused on resolving possible
      sub-assemblages within Assemblages A and B to better understand host-specific and
      zoonotic relationships. In the present study nine cloned, cultured, Assemblage B
      isolates were used to investigate the intra-Assemblage B substitution patterns of
      conserved (ssrDNA, ef, h2b, h4) and variable (tpi, gdh, bg) genes to assess their
      suitability for further application to sub-assemblage analyses. The resolution of
      each gene was found to be proportional to its substitution rate and for the
      genetically narrow sample set examined, the variable genes best represented the
      consensus phylogeny while the conserved genes only established fractions. However
      it was demonstrated that the spectra of conserved and variable genes were
      required to ensure accuracy of inferred phylogeny and it was therefore concluded
      that further research into sub-Assemblage B groups would require a mixture of
      conserved and variable genes for the multi-locus analyses of this genetically
      broad assemblage.

PMID- 21176782
TI  - Incorporation of caffeine into a quantitative model of fatigue and sleep.
AB  - A recent physiologically based model of human sleep is extended to incorporate
      the effects of caffeine on sleep-wake timing and fatigue. The model includes the
      sleep-active neurons of the hypothalamic ventrolateral preoptic area (VLPO), the
      wake-active monoaminergic brainstem populations (MA), their interactions with
      cholinergic/orexinergic (ACh/Orx) input to MA, and circadian and homeostatic
      drives. We model two effects of caffeine on the brain due to competitive
      antagonism of adenosine (Ad): (i) a reduction in the homeostatic drive and (ii)
      an increase in cholinergic activity. By comparing the model output to
      experimental data, constraints are determined on the parameters that describe the
      action of caffeine on the brain. In accord with experiment, the ranges of these
      parameters imply significant variability in caffeine sensitivity between
      individuals, with caffeine's effectiveness in reducing fatigue being highly
      dependent on an individual's tolerance, and past caffeine and sleep history.
      Although there are wide individual differences in caffeine sensitivity and thus
      in parameter values, once the model is calibrated for an individual it can be
      used to make quantitative predictions for that individual. A number of
      applications of the model are examined, using exemplar parameter values,
      including: (i) quantitative estimation of the sleep loss and the delay to sleep
      onset after taking caffeine for various doses and times; (ii) an analysis of the
      system's stable states showing that the wake state during sleep deprivation is
      stabilized after taking caffeine; and (iii) comparing model output successfully
      to experimental values of subjective fatigue reported in a total sleep
      deprivation study examining the reduction of fatigue with caffeine. This model
      provides a framework for quantitatively assessing optimal strategies for using
      caffeine, on an individual basis, to maintain performance during sleep
      deprivation.

PMID- 21176783
TI  - Dynamic activation model for a glutamatergic neurovascular unit.
AB  - This article considers a dynamic spatially lumped model for brain energy
      metabolism and proposes to use the results of a Markov chain Monte Carlo (MCMC)
      based flux balance analysis to estimate the kinetic model parameters. By treating
      steady state reaction fluxes and transport rates as random variables we are able
      to propagate the uncertainty in the steady state configurations to the
      predictions of the dynamic model, whose responses are no longer individual but
      ensembles of time courses. The kinetic model consists of five compartments and is
      governed by kinetic mass balance equations with Michaelis-Menten type expressions
      for reaction rates and transports between the compartments. The neuronal
      activation is implemented in terms of the effect of neuronal activity on
      parameters controlling the blood flow and neurotransmitter transport, and a
      feedback mechanism coupling the glutamate concentration in the synaptic cleft and
      the ATP hydrolysis, thus accounting for the energetic cost of the membrane
      potential restoration in the postsynaptic neurons. The changes in capillary
      volume follow the balloon model developed for BOLD MRI. The model follows the
      time course of the saturation levels of the blood hemoglobin, which link
      metabolism and BOLD FMRI signal. Analysis of the model predictions suggest that
      stoichiometry alone is not enough to determine glucose partitioning between
      neuron and astrocyte. Lactate exchange between neuron and astrocyte is supported
      by the model predictions, but the uncertainty on the direction and rate is rather
      elevated. By and large, the model suggests that astrocyte produces and effluxes
      lactate, while neuron may switch from using to producing lactate. The level of
      ATP hydrolysis in astrocyte is substantially higher than strictly required for
      neurotransmitter cycling, in agreement with the literature.

PMID- 21176784
TI  - The safety of modafinil in combination with oral ?9-tetrahydrocannabinol in
      humans.
AB  - Marijuana (cannabis) is the most widely used illicit substance globally, and
      cannabis use is associated with a range of adverse consequences. Currently, no
      medications have been proven to be effective for the treatment of cannabis
      addiction. The goals of this study were to examine the safety and efficacy of a
      potential treatment medication, modafinil, in combination with oral ?9
      tetrahydrocannabinol (THC). Twelve male and female occasional cannabis users
      participated in an outpatient double-blind, placebo-controlled, crossover study.
      Across four sessions, participants were randomly assigned to a sequence of four
      oral treatments: (1) 400 mg modafinil+placebo, (2) 15 mg THC+placebo, (3) 400 mg
      modafinil+15 mg THC, or (4) placebo+placebo. Outcome measures included heart
      rate, blood pressure, performance on the Rapid Visual Information Processing
      (RVIP), and the Hopkins Verbal Learning Test (HVLT), and subjective measures.
      Oral THC increased heart rate, and produced increased subjective ratings of
      feeling "high" and "sedated," as well as increased ratings of euphoria. Modafinil
      alone increased the Profiles of Mood States (POMS) subscales of vigor and
      tension. These findings support the safety of modafinil in combination with THC.
      The effects of modafinil in combination with a range of doses of THC need to be
      determined in future studies.

PMID- 21176786
TI  - Conversion of bacterially expressed recombinant prion protein.
AB  - The infectivity associated with prion disease sets it apart from a large group of
      late-onset neurodegenerative disorders that shares the characteristics of protein
      aggregation and neurodegeneration. The unconventional infectious agent, PrP(Sc),
      is an aberrantly folded form of the normal prion protein (PrP(C)) and the PrP(C)
      to-PrP(Sc) conversion is a critical pathogenic step in prion disease. Using the
      Protein Misfolding Cyclic Amplification technique, we converted folded
      bacterially expressed recombinant PrP into a proteinase K-resistant and
      aggregated conformation (rPrP-res) in the presence of anionic lipid and RNA
      molecules. Moreover, high prion infectivity was demonstrated by intracerebral
      inoculation of rPrP-res into wild-type mice, which caused prion disease with a
      short incubation period. The establishment of the in vitro recombinant PrP
      conversion assay makes it feasible for us to explore the molecular basis behind
      the intriguing properties associated with prion infectivity.

PMID- 21176787
TI  - Effects of sublethal irradiation on patterns of engraftment after murine bone
      marrow transplantation.
AB  - Attempts to reduce the toxicity of hematopoietic stem cell transplantation have
      led to the use of various immunosuppressive, yet nonmyeloablative preparative
      regimens that often include low-dose irradiation. To determine the effects of low
      dose irradiation on the dynamics of donor cell engraftment after bone marrow
      transplantation (BMT), we coupled standard endpoint flow cytometric analysis with
      in vivo longitudinal bioluminescence imaging performed throughout the early (<10
      days) and late (days 10-90) post-BMT periods. To exclude the contribution of
      irradiation on reducing immunologic rejection, severely immune-deficient mice
      were chosen as recipients of allogeneic bone marrow. Flow cytometric analysis
      showed that sublethal doses of total body irradiation (TBI) significantly
      increased long-term (14 weeks) donor chimerism in the bone marrow compared with
      nonirradiated recipients (P < .05). Bioluminescence imaging demonstrated that the
      effect of TBI (P < .001) on chimerism occurred only after the first 7 days post
      BMT. Flow cytometric analysis on day 3 showed no increase in the number of donor
      cells in irradiated bone marrow, confirming that sublethal irradiation does not
      enhance marrow chimerism early after transplantation. Local irradiation also
      significantly increased late (but not early) donor chimerism in the irradiated
      limb. Intrafemoral injection of donor cells provided efficient early chimerism in
      the injected limb, but long-term systemic donor chimerism was highest with i.v.
      administration (P < .05). Overall, the combination of TBI and i.v. administration
      of donor cells provided the highest levels of long-term donor chimerism in the
      marrow space. These findings suggest that the major effect of sublethal
      irradiation is to enhance long-term donor chimerism by inducing proliferative
      signals after the initial phase of homing.

PMID- 21176785
TI  - Neuroinflammation modulates distinct regional and temporal clinical responses in
      ALS mice.
AB  - An inflammatory response is a pathological hallmark of amyotrophic lateral
      sclerosis (ALS), a relentless and devastating degenerative disease of
      motoneurons. This response is not simply a late consequence of motoneuron
      degeneration, but actively contributes to the balance between neuroprotection and
      neurotoxicity; initially infiltrating lymphocytes and microglia slow disease
      progression, while later, they contribute to the acceleration of disease. Since
      motor weakness begins in the hindlimbs of ALS mice and only later involves the
      forelimbs, we determined whether differential protective versus injurious
      inflammatory responses in the cervical and lumbar spinal cords explained the
      temporally distinct clinical disease courses between the limbs of these mice.
      Densitometric evaluation of immunohistochemical sections and quantitative RT-PCR
      (qRT-PCR) demonstrated that CD68 and CD11c were differentially increased in their
      spinals cords. qRT-PCR revealed that protective and anti-inflammatory factors,
      including BDNF, GDNF, and IL-4, were increased in the cervical region compared
      with the lumbar region. In contrast, the toxic markers TNF-alpha, IL-1beta and
      NOX2 were not different between ALS mice cervical and lumbar regions. T
      lymphocytes were observed infiltrating lumbar spinal cords of ALS mice prior to
      the cervical region; mRNA levels of the transcription factor gata-3 (Th2
      response) were differentially elevated in the cervical cord of ALS mice whereas t
      bet (Th1 response) was increased in the lumbar cord. These results reinforce the
      important balance between specific protective/injurious inflammatory immune
      responses in modulating clinical outcomes and suggest that the delayed forelimb
      motor weakness in ALS mice is partially explained by augmented protective
      responses in the cervical spinal cords.

PMID- 21176788
TI  - Hyphal and cytoskeleton polarization in Tuber melanosporum: a genomic and
      cellular analysis.
AB  - Filamentous polarized growth involves a series of events including polarization
      of the cytoskeleton to selected growth sites, and the transport of secretory
      vesicles containing the components required for growth. The availability of
      fungal genome sequences has recently led to the identification of a large number
      of proteins involved in these processes. We have explored the Tuber melanosporum
      genome sequence by searching for homologs of genes known to play crucial roles in
      the morphogenesis and cell polarity of yeasts and filamentous fungi. One hundred
      and forty-nine genes have been identified and functionally grouped according to
      the deduced amino acid sequences (44 genes involved in cell
      polarity/morphogenesis, 39 belonging to the actin cytoskeleton and 66 involved in
      membrane dynamics, septation and exocytosis). A detailed gene annotation has
      shown that most components of the cell polarity machinery, morphogenesis and
      cytoskeleton found in yeasts and filamentous fungi are conserved, although the
      degree of similarity varies from strong to weak. Microscopic analysis of quick
      frozen truffle hyphae detected the characteristic subcellular components of the
      hyphal tip in septate filamentous fungi, while transcript profiles revealed a
      moderately variable pattern during the biological cycle.

PMID- 21176789
TI  - The osmosensing signal transduction pathway from Botrytis cinerea regulates cell
      wall integrity and MAP kinase pathways control melanin biosynthesis with
      influence of light.
AB  - Mitogen activated protein kinase (MAPK) signal transduction pathways are
      ubiquitous among eukaryotic organisms with evolutionary conserved modules.
      Although generally classified as osmotic and cell wall integrity pathways,
      functional divergences have been observed for HOG1- and SLT2-related MAPK
      pathways. Here we show that the osmotic signal transduction cascade is involved
      in cell wall integrity in the phytopathogenic ascomycete Botrytis cinerea. The
      deletion mutants of the upstream histidine kinase Bos1 and of the MAPK Sak1
      showed modified tolerance to cell wall degrading enzymes and cell wall
      interfering agents, as well as increased staining of beta1-3 glucan and chitin
      compared to the wild-type. The Sak1 MAPK was phosphorylated upon cell wall
      challenging. Sak1 interfered with the phosphorylation status of the SLT2 type
      MAPK Bmp3 hinting to cross talk between both MAPK pathways. All signal
      transduction components interfered with the expression of melanin biosynthesis
      genes in dark and bright, suggesting a coordinated control of melanin
      biosynthesis.

PMID- 21176790
TI  - Characterization of a polyketide synthase in Aspergillus niger whose product is a
      precursor for both dihydroxynaphthalene (DHN) melanin and naphtho-gamma-pyrone.
AB  - The genome sequencing of the fungus Aspergillus niger uncovered a large cache of
      genes encoding enzymes thought to be involved in the production of secondary
      metabolites yet to be identified. Identification and structural characterization
      of many of these predicted secondary metabolites are hampered by their low
      concentration relative to the known A. niger metabolites such as the naphtho
      gamma-pyrone family of polyketides. We deleted a non-reducing PKS gene in A.
      niger strain ATCC 11414, a daughter strain of A. niger ATCC strain 1015 whose
      genome was sequenced by the DOE Joint Genome Institute. This PKS encoding gene we
      name albA is a predicted ortholog of alb1 from Aspergillus fumigatus which is
      responsible for production of the naphtho-gamma-pyrone precursor for the 1,8
      dihydroxynaphthalene (DHN) melanin/spore pigment. Our results show that the A.
      nigeralbA PKS is responsible for both the production of the spore pigment
      precursor and a family of naphtho-gamma-pyrones commonly found in significant
      quantity in A. niger culture extracts. The generation of an A. niger strain
      devoid of naphtho-gamma-pyrones will greatly facilitate the elucidation of
      cryptic biosynthetic pathways in this organism.

PMID- 21176791
TI  - Glycomics of a novel type-2 N-acetyllactosamine-specific lectin purified from the
      feather star, Oxycomanthus japonicus (Pelmatozoa: Crinoidea).
AB  - A lectin - designated OXYL for the purposes of this study that strongly
      recognizes complex-type oligosaccharides of serum glycoproteins - was purified
      from a crinoid, the feather star Oxycomanthus japonicus, the most basal group
      among extant echinoderms. OXYL was purified through a combination of anion
      exchange and affinity chromatography using Q-sepharose and fetuin-sepharose gel,
      respectively. Lectin was determined to be a 14-kDa polypeptide by sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis under reducing conditions. However,
      14-kDa and 28-kDa bands appeared in the same proportion under non-reducing
      conditions. Gel permeation chromatography showed a 54-kDa peak, suggesting that
      lectin consists of four 14-kDa subunits. Divalent cations were not indicated, and
      stable haemagglutination activity was demonstrated at pH 4-12 and temperatures
      below 60 degrees C. Surface plasmon resonance analysis of OXYL against fetuin
      showed k(ass) and k(diss) values of 1.4*10(-6)M(-1)s(-1) and 3.1*10(-3)s(-1),
      respectively, indicating that it has a strong binding affinity to the
      glycoprotein as lectin. Frontal affinity chromatography using 25 types of
      prydylamine-conjugated glycans indicated that OXYL specifically recognizes multi
      antennary complex-type oligosaccharides containing type-2 N-acetyllactosamines
      (Galbeta1-4GlcNAc) if alpha2-3-linked sialic acid is linked at the non-reducing
      terminal. However, type-1 N-acetyllactosamine (Galbeta1-3GlcNAc) chains and
      alpha2-6-linked sialic acids were never recognized by OXYL. This profiling study
      showed that OXYL essentially recognizes beta1-4-linkage at C-1 position and free
      OH group at C-6 position of Gal in addition to the conservation of N-acetyl
      groups at C-2 position and free OH groups at C-3 position of GlcNAc in N
      acetyllactosamine. This is the first report on glycomics on a lectin purified
      from an echinoderm belonging to the subphylum Pelmatozoa.

PMID- 21176792
TI  - Segregation of open Major Histocompatibility Class I conformers at the plasma
      membrane and during endosomal trafficking reveals conformation-based sorting in
      the endosomal system.
AB  - Fully conformed Major Histocompatibility Class I molecules are complexes of heavy
      chain non-covalently associated with the peptide and beta-2-microglobulin.
      Conformational change in the extracellular domain of heavy chain leads to their
      disassembly and formation of open conformers, a process that physiologically
      occurs in normal cells and results in their presence at the cell surface. In this
      study we characterized endosomal trafficking of open conformers of a murine class
      I allele in order to examine whether conformational change in the extracellular
      domain of a membrane glycoprotein determines its endosomal sorting. Open
      conformers segregated from their fully conformed counterparts at the plasma
      membrane and in endosomes by sequestration in lipid-organized membrane
      environment. Consequently, open conformers constitutively internalized via
      distinct clathrin-independent endocytic carriers and converged into "classical"
      early endosomes together with transferrin receptor and cholera-toxin B subunit.
      In early endosomes, open conformers were excluded from recycling and diverted
      towards late endosomes. Due to lack of recycling, open conformers were
      constitutively internalized at a higher rate than full conformed proteins.
      Concanamycin A, methyl-beta-cyclodextrin and sphingomyelinase treatment prevented
      segregation of open conformers in vacuolar early endosomes indicating that acidic
      endosomal environment and membrane composition are critical for the maintenance
      of the sorting mechanism. In the absence of endosomal acidification open
      conformers partitioned into lipid disordered membrane composition of early
      endosomes. Thus, our data suggest for the existence of a lipid-dependent
      mechanism in the endosomal system that distinguish membrane proteins based on
      conformation of their extracellular domain.

PMID- 21176793
TI  - Preface: Current concepts in the treatment of the rheumatoid hand, wrist and
      elbow.

PMID- 21176794
TI  - Historical perspective on the etiology of rheumatoid arthritis.
AB  - Contributions of historical analyses to the development of a cogent etiologic
      theory of rheumatoid arthritis (RA) have been limited to date. In this article,
      the authors analyze this literature with respect to the types and conclusions of
      the research that has been conducted, present the major points of evidence and
      conclusions that have been drawn, and trace the evolution of 3 historical
      theories of RA. The authors combine a comprehensive overview of paintings and
      paleopathological investigations with consideration of contemporary immunologic
      and genetic studies.

PMID- 21176795
TI  - Advances in the medical treatment of rheumatoid arthritis.
AB  - Over the past 2 decades, the treatment of rheumatoid arthritis (RA) has been
      revolutionized by advances in the understanding of its pathologic mechanisms and
      the development of drugs that target them. These newer medications have shown
      great promise at improving disease outcomes, but they come with notable side
      effects that can pose long-term treatment challenges and difficulties in the
      perioperative arena. In this article, the major manifestations of RA and the
      current medical options for management are discussed. Complications from
      treatment are then reviewed, and special consideration is given to perioperative
      medication recommendations.

PMID- 21176796
TI  - Controversy in the surgical treatment of the rheumatoid hand.
AB  - The clinical picture of rheumatoid arthritis (RA) is best viewed as a combination
      of systemic symptoms associated with the inflammatory process and articular
      symptoms related both to potentially reversible synovitis and structural damage
      brought on by inflammation. In simple terms, the treatment of inflammation is
      medical, and structural lesions often require surgical solutions. The prime
      indications for surgery in patients with RA are essentially determined by the
      patient and consist of a desire to obtain pain relief and/or functional
      improvement. Pain is difficult to quantify. Essential concepts regarding surgical
      intervention are that surgery is elective in all but a few rare situations and
      always requires local therapy. Any evaluation of surgical intervention must be
      based on its total effect on the patient. Although there have been immense
      advances in the surgical options for patients with rheumatoid arthritis over the
      last several decades, the role of specific procedures in the total picture has
      many areas of uncertainty and controversy.

PMID- 21176797
TI  - Controversy in the treatment of the rheumatoid hand: perspective from hand
      surgery.
AB  - Over the years there has been controversy between rheumatologists and surgeons
      regarding surgery for the correction of rheumatoid problems. There are many
      reasons for this controversy. This article explores the reasons for the
      controversy, presents the history of rheumatoid hand surgery, and offers some
      possible solutions to the problem.

PMID- 21176798
TI  - Current concepts in the surgical management of rheumatoid and osteoarthritic
      hands and wrists.
AB  - Rheumatoid arthritis (RA) is a progressively destructive disease. Gradual loss of
      hand function in RA patients affects their ability for self-care and interferes
      with their productivity in society. The continuing improvement in the medical
      management of RA has markedly decreased the incidence of RA hand surgery. In
      contrast to RA, osteoarthritis (OA) has less inflammatory reaction in the joints
      and is characterized by degradation of cartilage, resulting in joint destruction
      and osteophyte formation. The initial treatment of OA is medication and therapy.
      Steroid injection into affected joints can provide short-term relief, though
      repeat injections carry a cumulative risk of weakening the soft tissue. In this
      article the authors share their extensive experience in RA and OA hand surgery to
      provide a clear discussion of the indications and outcomes of its practice.

PMID- 21176799
TI  - Rheumatoid elbow.
AB  - The elbow is often involved in the progression of rheumatoid arthritis. Because
      of the elbow's unique role in maneuvering and positioning the hand in space, loss
      of normal elbow motion, loss of stability, or increased pain with the use of the
      elbow are all significant sources of impairment in patients with rheumatoid
      arthritis. The improvements in disease-modifying medications have greatly
      diminished the prevalence of severe elbow degeneration among patients with
      rheumatoid arthritis. However, it hasn't been eliminated. In this article the
      authors discuss strategies for managing it.

PMID- 21176800
TI  - Current concepts in the treatment of rheumatoid arthritis of the distal
      radioulnar joint.
AB  - Rheumatoid arthritis (RA) may progressively affect all articulations of the
      wrist. Involvement of the distal radioulnar joint (DRUJ) is common and may be the
      first clinical signs of symptoms of RA. When the DRUJ is affected by RA, upper
      extremity function can be affected. Effective surgical management includes the
      Darrach procedure, the Suave-Kapandji procedure, the hemiresection interposition
      arthroplasty procedure and extensor tenosynovectomy. The long-term effectiveness
      of DRUJ arthroplasty is currently unknown.

PMID- 21176801
TI  - Current concepts and treatment for the rheumatoid wrist.
AB  - Wrist involvement in rheumatoid arthritis (RA) is common. Within 2 years of
      diagnosis, more than half of patients will have wrist pain, and more than 90%
      will have wrist disease by 10 years. Although wrist involvement is generally
      thought to be less disabling than RA of the fingers and hand, it can be a
      significant cause of pain and disability. Severe disease with bony destruction
      and synovitis in the wrist can also result in soft-tissue problems including
      tendon ruptures. In addition to musculoskeletal involvement, systemic
      manifestations of RA can occur. Felty syndrome can result in a low white blood
      count and splenomegaly in association with RA. New generation, disease-modifying
      pharmacologic agents offer promise in controlling the disease progression.
      Surgical treatments for the diseased wrist are aimed at relieving pain and
      restoring function. Common procedures include: synovectomy and tenosynovectomy,
      tendon reconstruction, distal ulnar resection and/or distal radioulnar joint
      reconstruction, partial and full wrist arthrodesis, and total wrist arthroplasty.

PMID- 21176802
TI  - Rheumatoid thumb.
AB  - The hand is the main tactile sensory organ and is uniquely designed for fine
      motor activities. Any deviation from the normal architecture or limitation from a
      painful condition may lead to disability. Rheumatoid arthritis (RA) is
      fundamentally an inflammatory disease of the soft tissues. Deformities of the
      thumb arise from abnormal stretching of ligament and capsular structures as well
      as from ruptures and subluxations of the tendons. This article provides an
      overview of the types of deformities associated with, and surgical management of,
      RA of the thumb.

PMID- 21176803
TI  - The rheumatoid metacarpophalangeal joint.
AB  - Rheumatoid metacarpophalangeal joint deformities remain an important cause of
      disability. Surgical intervention in carefully selected patients improves
      function and prolongs independence. This article discusses the commonly used
      reconstructive techniques and their benefits. Case selection through a combined
      clinic with rheumatologists and hand therapists is recommended.

PMID- 21176804
TI  - Reconstruction of digital deformities in rheumatoid arthritis.
AB  - Digital deformities result from rheumatoid synovitis. These deformities are
      easier to treat in the early stage, when the deformity is passively correctable.
      Treatment options become limited as the disease progresses and the deformity
      becomes fixed. Surgical treatment of digital deformities is last in the priority
      of surgical procedures for the rheumatoid hand and wrist. It is therefore
      important to understand the patient's needs and expectations for improvement and
      attempt to match them with the surgical options that can predictably improve the
      patient's function. A close collaboration with the patient's rheumatologist is
      helpful in the overall management of patients.

PMID- 21176805
TI  - Tendon reconstruction for the rheumatoid hand.
AB  - Tendon involvement in rheumatoid arthritis is frequent and might even be the
      first sign of the disease. In long-standing untreated conditions, especially in
      combination with bony erosions, tenosynovitis may lead to tendon fraying and
      finally tendon rupture. Tendon reconstruction includes tendon grafting and tendon
      transfer. Direct repair is almost never possible in patients with rheumatoid
      arthritis, because the inflammatory process produces extensive tendon damage over
      a long distance. In patients with significant impaired joint function, additional
      joint treatment should be planned at the same time as tendon reconstruction.

PMID- 21176806
TI  - Outcomes research in rheumatoid arthritis.
AB  - Although rheumatoid arthritis causes significant disability for more than 1
      million individuals in the United States, prior research regarding surgical
      treatment options has been limited by study sample size, study design, and
      methods of comparison. Furthermore, there is wide variation in the referral
      pattern for hand surgery consideration and type of surgical treatment of
      rheumatoid hand disease, yet the reasons for these differences are unclear. This
      review describes the role of outcomes research in rheumatoid hand disease by
      summarizing variations in surgical treatment, detailing current outcome
      assessment strategies, and offering potential strategies for designing future
      studies for rheumatoid hand disease.

PMID- 21176807
TI  - Hereditary hemochromatosis of tongue.
AB  - Hereditary hemochromatosis (HH) refers to several inherited disorders of iron
      metabolism leading to tissue iron overload. Classical HH is associated with
      mutations in HFE (C282Y homozygotes or C282Y/H63D compound heterozygotes) and is
      almost exclusively found in populations of northern European descent. Non-HFE
      associated HH is caused by mutations in other recently identified genes involved
      in iron metabolism. Hepcidin is an iron regulatory hormone that inhibits
      ferroportin-mediated iron export from enterocytes and macrophages. Defective
      hepcidin gene expression or function may underlie most forms of HH. Target organs
      and tissues affected by HH include the liver, heart, pancreas, joints, and skin,
      with cirrhosis and diabetes mellitus representing late signs of disease in
      patients with markedly elevated liver iron concentration. Recently, we have
      encountered the rare representation of this disease of the oral cavity associated
      with generalized burning sensation of the tongue. The diagnosis was established
      accidently, from the lab investigations, otherwise the patient was healthy and
      free from classical signs and symptoms of the disease. The patient was adequately
      treated by phlebotomy. To conclude, all patients with a chief complaint of
      burning sensation of the oral cavity and tongue should be adequately screened for
      hereditary hemochromatosis to prevent the associated mortality and morbidity with
      the hemochromatosis.

PMID- 21176808
TI  - In vivo bone regenerative effect of low-intensity pulsed ultrasound in rat
      calvarial defects.
AB  - OBJECTIVES: Low-intensity pulsed ultrasound (LIPUS) is a biophysical intervention
      in a bone repair process. However, neither the healing events of the flat bones
      of the skull using LIPUS nor the optimal stimulation settings are fully
      understood. The aim of this study was to evaluate the bone regenerative effect of
      LIPUS in rat calvarial flat bone defects by using in vivo microfocus computerized
      tomography (micro-CT). STUDY DESIGN: The calvarium was exposed, and noncritical
      sized 2.7-mm defects were prepared. LIPUS (1.6 MHz, repeating 1.0-kHz pulsation,
      and 30-mW/cm(2) intensity) was applied for 20 minutes daily. Bone regeneration
      was evaluated by image analysis using micro-CT and histologic examination.
      RESULTS: Within 2 weeks, LIPUS-treated rats demonstrated 7.0% reossification of
      the original surgical defect, whereas control rats demonstrated 3.6%. At 3 and 4
      weeks, a significant difference in the reossification ratio was observed (12.0%
      vs. 5.8% and 18.1% vs. 9.8%, respectively; P < .05). CONCLUSIONS: LIPUS
      accelerated bone regeneration of noncritical rat calvarial defects as confirmed
      by micro-CT.

PMID- 21176809
TI  - The frequency and distribution pattern of minor salivary gland tumors in a
      government dental teaching hospital, Chennai, India.
AB  - OBJECTIVES: Data are not available regarding distribution of minor salivary gland
      tumors from the specialist pathology setting in India. The purpose of this study
      was to determine the relative frequency and distribution of minor salivary gland
      tumors and to compare the data with pertinent studies. STUDY DESIGN: The records
      and archival samples of the Department of Oral and Maxillofacial Pathology, Tamil
      Nadu Government Dental College and Hospital, Chennai, India, served as source
      material for this retrospective study. All cases with a diagnosis of minor
      salivary gland tumors recorded between 1971 and August 2008 were retrieved and
      reviewed. RESULTS: A total of 185 minor salivary gland tumors were identified
      with reference to the latest World Health Organization classification,
      representing a relative frequency of 1.52% over the study period of 37 years
      (1971-2008) from 12,147 biopsy samples. Malignant tumors (75%) predominated over
      benign tumors (25%). The age range was 12-82 years with a mean of 46 years.
      Mucoepidermoid carcinoma was the most frequent tumor (34%), followed by
      pleomorphic adenoma (22%), adenoid cystic carcinoma (15%), and polymorphous low
      grade adenocarcinoma (10%). The overall gender distribution was almost equal.
      Palate was the most frequent involved site, followed by alveolar mucosa and floor
      of the mouth. CONCLUSIONS: The present study shows a higher proportion of
      malignant tumors and a tendency toward male predilection during the past decades.
      The overall data are consistent with hospital-based studies from Asia and series
      from other geographic regions.

PMID- 21176810
TI  - Frequency and distribution of root filled teeth and apical periodontitis in a
      Jordanian subpopulation.
AB  - OBJECTIVE: The aim of this study was to evaluate the prevalence and distribution
      of apical periodontitis and endodontic treatment in a Jordanian subpopulation.
      STUDY DESIGN: Digital panoramic radiographs of 294 patients who were assessed at
      Caritas Association between January and September 2008 were evaluated. The
      coronal and periapical status of all visible teeth were evaluated according to
      the criteria proposed by de Moor et al. RESULTS: Of the 294 subjects assessed,
      83.7% had apical periodontitis and 63.3% had endodontically treated teeth. Of the
      7,390 teeth assessed, 11.6% had apical periodontitis and 5.7% were endodontically
      treated. A correlation was found between apical periodontal lesions and
      endodontically treated teeth. Endodontic treatment was inadequate in 72.4% of the
      endodontically treated teeth, of which 87.0% had apical periodontitis. No
      difference in the number of endodontically treated teeth or the presence of
      apical periodontitis was found between male and female subjects (P > .05).
      CONCLUSIONS: The results of this study indicate that there is a relatively higher
      prevalence of apical periodontitis compared with those of many other countries.
      High percentage of endodontically treated teeth was inadequate and associated
      with periapical pathosis, indicating a poor quality of endodontic treatment.

PMID- 21176811
TI  - Factors affecting changes in sinus graft height between and above the placed
      implants.
AB  - OBJECTIVE: The aim of this study was to compare the radiographic dimensional
      changes of sinus graft height above and between placed implants, and evaluate the
      factors effecting these changes with 2 different grafting materials and both
      combination. STUDY DESIGN: The study group comprised 42 patients (50 sinus
      augmentation procedures). Four consecutive panoramic radiographs were evaluated
      for changes in sinus graft height between and above the placed implants. Factors
      that may influence graft height reduction were evaluated. RESULTS: The mean
      percentage of autogenous bone height reduction was 23% between implants and 13%
      above the implants. Bovine xenograft showed a mean of 6.5% graft height reduction
      between implants and 0% above implants. The only 2 parameters that correlated
      with reduction of graft height above and between the implants were time elapsed
      from surgery and the type of bone graft. Autogenous bone graft presented
      significantly more reduction (P = .022), whereas anorganic bovine bone graft had
      only minor or no changes in height. CONCLUSION: The most important factor
      influencing reduction in vertical bone height on the time axis, following sinus
      augmentation is the grafting material, followed by the presence of a functional
      implant. Anorganic bovine bone was found superior in graft height maintenance in
      an up to 10 years of follow-up.

PMID- 21176813
TI  - Free flap reconstruction of the maxilla: is there something missing?

PMID- 21176815
TI  - A histopathologic comparison between synchronous and single primary oral squamous
      cell carcinomas.

PMID- 21176817
TI  - Research and publication ethics: what have we learned thus far?

PMID- 21176818
TI  - Association of oral lichen planus with thyroid disease in a Finnish population: a
      retrospective case-control study: "A different finding from a Mediterranean
      area".

PMID- 21176820
TI  - A 78-year-old woman with bilateral tongue necrosis.

PMID- 21176821
TI  - Dental considerations in the patient with Wilson's disease.
AB  - Wilson's disease was described by Wilson in 1912. It is an autosomal recessive
      disorder caused by mutations in the ATP7B gene, a membrane-bound copper
      transporting ATPase. The deficiency of ATP7B protein impairs the biliary copper
      excretion, resulting in positive copper balance, hepatic copper accumulation, and
      copper toxicity from oxidant damage. The disease is a form of copper poisoning
      caused by a defect in the transport of copper that renders the patient unable to
      handle trace amounts of copper normally present in the diet and hence the
      clinical manifestations are those typically caused by copper toxicity and
      primarily involve the liver and the brain. Because effective treatment is
      available, it is important to make an early diagnosis. In this article, a review
      of clinical aspects of Wilson's disease, and its impact on dental management and
      dental considerations are discussed.

PMID- 21176822
TI  - Recovery of salivary epidermal growth factor in parotid saliva following parotid
      sparing radiation therapy: a proof-of-principle study.
AB  - BACKGROUND: Although radiation therapy (RT) causes permanent xerostomia, parotid
      sparing radiation therapy (PSRT) ensures recovery of saliva quantity over time.
      Salivary epidermal growth factor (EGF) is produced primarily by parotid glands.
      OBJECTIVES: The aim of this study was to determine whether salivary EGF can be
      detected in parotid saliva after PSRT and whether protein secretion is time
      dependent. STUDY DESIGN: Salivary EGF concentration (pg/mL) was determined by
      enzyme-linked immunosorbent assay in stimulated parotid saliva before RT and at
      3, 6, and 12 months after RT from 22 patients with head and neck cancer treated
      with PSRT. RESULTS: Saliva samples were from 17 men and 5 women (age ranges 23-70
      years and 46-71 years, respectively). At 6 months after RT, EGF concentration was
      407 pg/mL lower than at baseline (P = .045). Twelve months after PSRT, parotid
      glands produce substantial amounts of EGF and other proteins, eventually
      approximating pre-RT levels, with recovery of salivary function. CONCLUSIONS:
      This proof-of-principle study shows that even proteins in picogram quantities,
      such as EGF, can be detected in saliva after PSRT.

PMID- 21176823
TI  - Antimicrobial photodynamic therapy in rat experimental candidiasis: evaluation of
      pathogenicity factors of Candida albicans.
AB  - OBJECTIVE: This study evaluated the effects of photodynamic therapy on
      pathogenicity of Candida albicans. STUDY DESIGN: Fifty-six rats were submitted to
      development of candidiasis on the tongue dorsum by C. albicans inoculations.
      After 5 days, different treatments were administered: laser and photosynthesizer
      methylene blue (L+P+); laser only (L+P-); photosensitizer only (L-P+); and
      physiologic solution only (L-P-). Samples of the oral cavity were collected for a
      count of colony-forming units per mL. Colonies were isolated for evaluation of
      proteinase and phospholipase activities. The rats were killed for microscopic
      analysis of the tongue dorsum. The data were analyzed by analysis of variance,
      Kruskal-Wallis, and Bonferroni tests. RESULTS: The number of C. albicans
      recovered from the oral cavity of the rats was similar between the groups (P =
      .106). The L+P+ group showed fewer microscopic lesions of candidiasis than the L
      P- group (P = .001). The L+P+ group presented lower proteinase activity compared
      with the other groups, with significant difference between the groups L+P+ and L
      P+ (P = .018). CONCLUSIONS: Photodynamic therapy reduced the microscopic lesions
      of experimental candidiasis in rats and inhibited the proteinase activity of C.
      albicans.

PMID- 21176824
TI  - Morphologic evaluation of the inferior alveolar nerve in patients with sensory
      disorders by high-resolution 3D volume rendering magnetic resonance neurography
      on a 3.0-T system.
AB  - OBJECTIVE: The objective of this study was to evaluate the inferior alveolar
      nerve (IAN) morphologically in patients with symptomatic posttraumatic sensory
      disorders using magnetic resonance imaging (MRI) on a high-field system. STUDY
      DESIGN: Sixteen patients who complained of persistent sensory disturbance
      attributed to unilateral IAN injury participated in the investigation. High
      resolution 3-dimensional volume rendering magnetic resonance neurography was
      performed on a 3.0-T MRI system. RESULTS: In 15 (94%) of 16 patients, high
      resolution 3-dimensional volume rendering magnetic resonance neurography
      demonstrated morphologic abnormalities of the IAN as well as connective tissue
      overgrowth. These findings were confirmed intraoperatively (6 patients) and
      histopathologically (5 patients). The duration of sensory disturbance correlated
      significantly with the pattern of morphologic deformity and connective tissue
      overgrowth. CONCLUSIONS: The current study clearly demonstrated that appropriate
      application of clinical MRI techniques can significantly improve the diagnosis
      and potential treatment of patients with orofacial peripheral nerve disorders.

PMID- 21176825
TI  - Effect of low-surface-tension EDTA solutions on the wettability of root canal
      dentin.
AB  - OBJECTIVE: This study was conducted to evaluate the effect of reducing the
      surface tension of ethylenediaminetetraacetic acid (EDTA) solutions on the
      wettability of root canal dentin. STUDY DESIGN: Forty-two extracted teeth were
      sectioned at the crown, and the apical third and remaining mid-root portion was
      bisected longitudinally. The root halves were embedded in resin blocks. The
      experimental groups were treated with 17% EDTA, EDTA-T, and REDTA alone or
      followed by 2.5% NaOCl. Surface free energies of samples were calculated by
      measuring contact angles. Surface tension measurements of all solutions were
      performed with pendant drop method. RESULTS: The addition of surfactant to the
      EDTA solution significantly decreased the surface tension of solutions (P < .01).
      Combined and single use of experimental solutions and NaOCl significantly
      decreased the water contact angle and increased the surface free energy of root
      canal dentin (P < .05). EDTA-T alone or combined with NaOCl also increased
      surface free energy compared with EDTA solution (P < .05). CONCLUSIONS: The use
      of low-surface-tensioned EDTA compounds alone or in combination with NaOCl
      increased the wettability of root canal dentin.

PMID- 21176826
TI  - Comparative analysis of torsional and bending behavior through finite-element
      models of 5 Ni-Ti endodontic instruments.
AB  - OBJECTIVES: The objectives of this study were to compare numerically the bending
      and torsional mechanical behavior of 5 endodontic rotary Ni-Ti instruments with
      equivalent size and various designs for tapers, pitch, and cutting blades.First,
      the geometries of Hero (20/0.06), HeroShaper (20/0.06), ProFile (20/0.06), Mtwo
      (20/0.06), and ProTaper F1 were generated by finite element code. Then, the 2
      most representative clinical loadings, i.e., bending and torsion, were studied
      with an ad hoc model for the superelasticity of Ni-Ti. Bending was generated by
      tip deflection and torsion by a constant twist-angle of the tip. RESULTS:
      Mechanical behavior of these 5 endodontic rotary Ni-Ti instruments could be
      evaluated and compared. Protaper F1 presented the greatest level of bending
      stress and torque. Hero and HeroShaper were more rigid than ProFile and Mtwo.
      CONCLUSIONS: This numerical comparison evaluated the effects of the geometrical
      parameters on the instrumental mechanical behavior. The 5 endodontic instruments,
      investigated in the present study, do not have the same bending and torsional
      mechanical behavior. Each clinician must be aware of these behavior differences
      so as to use the adequate file according to the clinical situation and to the
      manufacturer's recommendations.

PMID- 21176827
TI  - Effect of selected accelerants on setting time and biocompatibility of mineral
      trioxide aggregate (MTA).
AB  - OBJECTIVE: Various additives have been suggested to be used with mineral trioxide
      aggregate (MTA) to improve its handling characteristics. The purpose of this
      study was to evaluate the effects of various additives on setting time and cell
      attachment on gray MTA (GMTA). STUDY DESIGN: Single-rooted caries-free teeth were
      split, and dentin disks with class I cavity were made and filled with test and
      control materials. Setting time was measured using Gilmore apparatus. Mouse MC3T3
      E1 osteoblasts and L929 mouse fibroblasts were grown on dentin and GMTA disks.
      Cell attachment was examined under fluorescent microscope. RESULTS: Adding KY
      liquid, CaCl(2), and NaOCl to GMTA improved the handling properties and decreased
      setting time. Osteoblasts and fibroblasts attached and spread on GMTA mixed with
      additives in a manner similar to GMTA mixed with water. CONCLUSIONS: The various
      additives could be possible substitutes to water to decrease MTA setting time.
      MTA is biocompatible when mixed with the various additives.

PMID- 21176828
TI  - Dentine caries inhibition through CO(2) laser (10.6MUm) irradiation and fluoride
      application, in vitro.
AB  - OBJECTIVE: The purpose of the study was to investigate whether dentine
      irradiation with a pulsed CO(2) laser (10.6MUm) emitting pulses of 10 ms is
      capable of reducing dentine calcium and phosphorus losses in an artificial caries
      model. DESIGN: The 90 dentine slabs obtained from bovine teeth were randomly
      divided into six groups (n=15): negative control group (GC); positive control
      group, treated with fluoride 1.23% (GF); and laser groups irradiated with 8
      J/cm(2) (L8); irradiated as in L8+fluoride 1.23% (L8F); irradiated with 11
      J/cm(2) (L11); irradiated as in L11+fluoride 1.23% (L11F). After laser
      irradiation the samples were submitted to a pH-cycling model for 9 days. The
      calcium and phosphorous contents in the de- and remineralization solutions were
      measured by means of inductively coupled plasma optical emission spectrometer-
      ICP-OES. Additionally intrapulpal temperature measurements were performed. The
      obtained data were analysed by means of ANOVA and Tukey's test (alpha=0.05).
      RESULTS: In the demineralization solutions the groups L11F and GF presented
      significantly lower means of calcium and phosphorous losses than the control
      group; and in L11F means were significantly lower than in the fluoride group.
      Both irradiation parameters tested caused intrapulpal temperature increase below
      2 degrees C. CONCLUSION: It can be concluded that under the conditions of this
      study, CO(2) laser irradiation (10.6 MUm) with 11 J/cm(2) (540 mJ and 10 Hz) of
      fluoride treated dentine surfaces decreases the loss of calcium and phosphorous
      in the demineralization process and does not cause excessive temperature increase
      inside the pulp chamber.

PMID- 21176829
TI  - [A case-control study of extracorporeal versus intracorporeal anastomosis in
      patients subjected to right laparoscopic hemicolectomy].
AB  - INTRODUCTION: There is still insufficient scientific evidence on which is the
      best technique to perform the anastomosis -intracorporeal (IC) or extracorporeal
      (EC)- in right laparoscopic hemicolectomy. The objective of the present study is
      to determine whether there are differences to compare in both techniques.
      MATERIAL AND METHODS: A study was performed on a prospective patient series
      subjected to right laparoscopic hemicolectomy in our Hospital. The preoperative
      and the postoperative variables associated with complications recorded depending
      on the type of anastomosis. RESULTS: A total of 60 patients were intervened form
      June 2004 to June 2010 (35 IC; 25 EC). There were no significant differences
      between both groups as regards baseline preoperative characteristics or
      associated comorbidities. The median operation time was 212 minutes (142-305
      min), with no significant difference between both techniques. The number of lymph
      nodes removed was higher in the IC group (21 versus 14; p=0.03). The beginning of
      oral tolerance and the first bowel movement were significantly earlier in the IC
      group. The complications rate was similar for both groups (14% IC; 16% EC;
      p=0.89). Three patients in the IC group had anastomosis dehiscence. The mortality
      rate was 2.8% (one patient in each group). CONCLUSION: Intracorporeal versus
      extracorporeal anastomosis in right laparoscopic hemicolectomy can obtain a
      higher number of resected lymph nodes and an earlier oral tolerance and
      intestinal transit.

PMID- 21176830
TI  - [Accreditation and certification in coloproctology in Europe].

PMID- 21176831
TI  - [Abdominoperineal resection in anal cancer: Reconstruction of the perineum with a
      myocutaneous flap from the anterior rectus abdominis muscle].
AB  - INTRODUCTION: Abdominoperineal resection after radiotherapy has a high rate of
      perineal wound complications. The aim of this retrospective study was to evaluate
      the results of perineal reconstruction with a rectus abdominis muscle
      myocutaneous flap in patients with recurrent or persistent anal cancer. PATIENTS
      AND METHOD: Between 2006 and 2010, six male HIV+ patients were treated after
      initial treatment failure with chemotherapy. An anterior rectal myocutaneous flap
      was performed after abdominal-perineal excision. RESULTS: The mean age was 36.3
      years (range: 30-42). Primary healing of the perineal wound was achieved in the
      first thirty days. There were no major complications in the immediate post
      surgical period or after a mean follow up of 26.5 months. There were 2 (33.3%)
      minor complications associated with the perineal wound. There were no
      complications of the abdominal wall. CONCLUSION: The use of an anterior rectus
      abdominis myocutaneous flap in patients with recurrent or persistent anal cancer
      is associated with a low rate of perineal complications.

PMID- 21176832
TI  - [Anastomotic dehiscence and recurrence of colorectal cancer: an association that
      strengthens the prognostic value of the surgeon in the oncological outcome].

PMID- 21176833
TI  - A systematic review of locking plate fixation of proximal humerus fractures.
AB  - PURPOSE: Technique for the fixation of two, three, and four part proximal humerus
      fractures has rapidly shifted towards the use of specially contoured proximal
      humerus locking plates. The purpose of this study is to evaluate the short to
      medium term functional results and common complications associated with the
      fixation of proximal humerus fractures with locking plates. METHODS: The PubMed
      and EMBASE databases were used to perform a systematic review of the English
      literature to assess the functional results and complications associated with
      proximal humerus locking plates. Our inclusion criteria were proximal humerus
      fracture due to trauma (excluding pathologic fractures), patients greater than 18
      years of age, more than 15 patients in the study or subgroup of interest, at
      least 18 months follow-up, at least one relevant functional outcome score, and
      quality outcome score of at least 5/10. Studies that did not meet these criteria
      were excluded. All institutional, author, and journal information was concealed
      to minimize reviewer bias. RESULTS: Twelve studies including 514 patients met the
      inclusion criteria. At most recent follow-up patients achieved a mean Constant
      score of 74 and a mean DASH score of 27. The overall rate of complications was
      49% including varus malunion, 33% excluding varus malunion, and reoperation rate
      was 14%. The most common complications included varus malunion 16%, AVN 10%,
      screw perforation of the humeral head into the joint 8%, subacromial impingement
      6%, and infection 4%. DISCUSSION: Fixation of proximal humerus fractures with
      proximal humerus locking plates is associated with a high rate of complications
      and reoperation. Further study is needed to determine what technical errors and
      patient characteristics are risk factors for failure of this now common fixation
      technique.

PMID- 21176834
TI  - Relationship of moderate metabolic risk factor clustering to cardiovascular
      disease mortality in non-lean Japanese: a 15-year follow-up of NIPPON DATA90.
AB  - OBJECTIVE: The individual components of metabolic syndrome are defined as levels
      ranging from moderate to high level as to require medication. We investigated the
      impact of moderate metabolic risk factor clustering on cardiovascular disease
      (CVD) mortality. METHODS: We followed up 6758 non-lean Japanese in randomly
      selected areas from all over the country who had no history of CVD for 15 years.
      The multivariate-adjusted hazards ratio (HR) and 95% confidence interval (CI) for
      CVD mortality according to the number of moderate metabolic risk factors (BMI>=25
      kg/m2, 130/85 mmHg<=systolic/diastolic BP<140/90 mmHg, 140 mg/dl<=casual blood
      glucose<200 mg/dl, triglycerides>=150 mg/dl and/or HDL cholesterol<40 mg/dl
      [men], 50 mg/dl [women]) were estimated using the Cox proportional hazards model.
      The population-attributable risk fraction of moderate metabolic risk factor
      clustering was also estimated. RESULTS: During the follow-up, 282 participants
      died of CVD. CVD mortality tended to increase with the number of moderate
      metabolic risk factors. However, they were not statistically significant. The
      multivariate-adjusted HRs were 1.82 (95%CI: 0.89-3.73) for having any moderate
      metabolic risk factors and 2.87 (95%CI: 1.46-5.64) for having any medication
      required metabolic risk factors, compared with participants without any moderate
      metabolic risk factors. The population-attributable risk fractions were 7.3% and
      52.4% for any moderate and medication-required metabolic risk factors,
      respectively. CONCLUSIONS: We did not find the statistically significant increase
      of CVD mortality for moderate metabolic risk factor clustering. Its attribution
      was relatively small in this Japanese population. More efforts would be required
      to detect and control medication-required risk factors.

PMID- 21176835
TI  - Gender differences in epicardial and tissue-level reperfusion in patients
      undergoing primary angioplasty for acute myocardial infarction.
AB  - OBJECTIVE: The impact of gender on clinical course after ST-elevation myocardial
      infarction (STEMI) is not fully understood. We prospectively investigated whether
      there are gender-related differences in epicardial and myocardial tissue-level
      perfusion, both of which represent important prognostic determinants in STEMI
      patients undergoing primary percutaneous coronary intervention (PPCI). METHODS: A
      total of 594 consecutive non-selected STEMI patients undergoing PPCI were
      prospectively enrolled. Primary end-point of the study was post-procedural
      epicardial and myocardial perfusion. Secondary end-points were the 30-day and 6
      month composite occurrence of major adverse cardiac events (MACE). RESULTS: Women
      with STEMI had higher risk factor profiles than men. Although PPCI achieved equal
      rates of successful epicardial reperfusion, women tended to have impaired
      microvascular reperfusion as reflected by lower rates of normal TIMI myocardial
      perfusion grade (P=0.007) and complete ST-segment resolution (P=0.079). After
      adjustment for the risk profiles, multivariable analysis showed that gender
      itself was not an independent predictor of impaired microvascular reperfusion.
      Both female gender and impaired myocardial reperfusion were independent
      predictors of 30-day MACE, whereas gender lost its prognostic significance for 6
      month MACE. Multivariable analysis restricted to female patients identified
      incomplete ST-segment resolution as the strongest determinant of 30-day MACE.
      CONCLUSION: The differences in microvascular reperfusion after PPCI between women
      and men are attributed to higher risk profiles in women. Both female gender and
      impaired myocardial reperfusion were independent predictors of 30-day outcomes
      after PPCI, emphasizing the importance of successful microvascular reperfusion in
      the women with STEMI.

PMID- 21176836
TI  - Determination of bile acids in pig liver, pig kidney and bovine liver by gas
      chromatography-chemical ionization tandem mass spectrometry with total ion
      chromatograms and extraction ion chromatograms.
AB  - An effective method has been developed for quantitative determination of six bile
      acids including lithocholic acid (LCA), deoxycholic acid (DCA), chenodeoxycholic
      acid (CDCA), hydodeoxycholic acid (HDCA), cholic acid (CA) and ursodeoxycholic
      acid (UDCA) in biological tissues including pig liver, pig kidney and bovine
      liver by gas chromatography-chemical ionization/tandem mass spectrometry (GC
      CI/MS/MS). Camphor-10-sulphonic acid (CSA) was proposed as effective catalyst for
      bile acid derivatization. Reactions were accelerated ultrasonically. The effects
      of different catalysts and reaction times on derivatization efficiency were
      evaluated and optimized. Bile acids were determined as methyl ester
      trimethylsilyl ether and methyl ester-acetate derivatives. The efficiency of
      trimethylsilylation and acetylation was evaluated. Trimethylsilylation was done
      with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) as the trimethylsilyl
      donating reagent in a ultrasonic bath for 20 min. Acetylation was done in
      pyridine with acetic anhydride at 40-45 degrees C for 4 h. The former reaction
      was faster than the latter. Thus, trimethylsilylation was employed for the
      quantitative analysis. Negligible interferences from sterols in biological
      matrices were observed when the biological samples were treated with solid phase
      extraction before GC-CI/MS/MS. The linearity, reproducibility, detection limit
      and recovery were evaluated under the optimized conditions. Satisfactory results
      were obtained when bile acid derivatives of LCA, CDCA, HDCA, and UDCA were
      determined with total ion chromatograms (TIC) while DCA and CA were determined
      with extracted ion chromatograms (EIC), respectively. The detection limits
      (S/N=3) for six bile acids in biological tissues were ranging from 0.40 to 1.6
      ng/mL and the recoveries indicated that the proposed method was feasible for the
      determination of trace bile acids in the biological samples studied. The
      experimental results for the animal tissues purchased from five different markets
      were compared. Interestingly, all of the six bile acids were present in pig liver
      while only the dihydroxy bile acids, DCA, CDCA and HDCA were found in pig kidney.
      In addition to DCA and CDCA, trihydroxy bile acid, CA, are the major bile acids
      in bovine liver.

PMID- 21176837
TI  - Optimization of peptide and protein separation with a monolithic reversed-phase
      column and application to arsenic-binding studies.
AB  - A separation method for a mixture of eight sulfur-containing peptides and
      proteins characterized by a wide molar mass (1-18.4 kDa) and pI range (4.5-10.7)
      was developed onto a monolithic phenyl phase. Based on the first optimization
      steps that revealed an increase of the acetonitrile content to 45 vol.% as
      sufficient for the elution of all biomolecules and the addition of the ion
      pairing reagent trichloroacetic acid (TCA) as preferable over the eluent
      additives formic acid or ammonium acetate buffer, the critical variables TCA
      concentration, gradient time, and eluent flow rate were optimized using a Box
      Behnken experimental design. To achieve optimum values for separation factors of
      all peak pairs, a TCA content of 0.025% (m/v), a gradient time of 10 min, and a
      flow rate of 3.5 mL min(-1) were selected. Arsenic binding studies were
      undertaken under conditions optimized with respect to the crucial separation
      factor of the nonapeptides vasotocin (Vtc) and vasopressin (Vpr) in a shortened
      gradient time of 7.5 min. A complete separation of phenylarsenic-substituted and
      unmodified forms of these peptides allowed the calculation of both consumptions
      and apparent equilibrium constants K from HPLC-UV peak areas. The nonapeptide
      consumptions by the reaction with phenylarsine oxide (PAO) increased from 7% up
      to 100% in dependence on the molar ratio of the reaction components. Due to an
      enhanced UV absorption of the phenylarsenic-substituted biomolecules, the
      calculation of apparent equilibrium constants led to increasing K values with
      rising PAO molarities from 9.6*10(5) to 1.2*10(8) in case of Vtc and from
      2.2*10(6) to 1.4*10(9) in case of Vpr. For alpha-lactalbumin, a consumption of
      59.2+/-6.1% by the reaction with molar excesses of PAO varying from 1.4 to 21 can
      be derived from the chromatograms. The quantitative evaluation of the reaction of
      the small protein aprotinin with PAO was hindered by a pronounced peak broadening
      that occurred after reduction of the disulfide bridges.

PMID- 21176838
TI  - Hydrophobic interaction chromatography of proteins. IV. Protein adsorption
      capacity and transport in preparative mode.
AB  - The adsorption isotherms of four model proteins (lysozyme, alpha-lactalbumin,
      ovalbumin, and BSA) on eight commercial phenyl hydrophobic interaction
      chromatography media were measured. The isotherms were softer than those usually
      seen in ion-exchange chromatography of proteins, and the static capacities of the
      media were lower, ranging from 30 to 110 mg/mL, depending on the ammonium sulfate
      concentration and the protein and adsorbent types. The protein-accessible surface
      area appears to be the main factor determining the binding capacity, and little
      correlation was seen with the protein affinities of the adsorbents. Breakthrough
      experiments showed that the dynamic capacities of the adsorbents at 10%
      breakthrough were 20-80% of the static capacities, depending on adsorbent type.
      Protein diffusivities in the adsorbents were estimated from batch uptake
      experiments using the pore diffusion and homogeneous diffusion models. Protein
      transport was affected by the adsorbent pore structures. Apparent diffusivities
      were higher at lower salt concentrations and column loadings, suggesting that
      adsorbed proteins may retard intraparticle protein transport. The diffusivities
      estimated from the batch uptake experiments were used to predict column
      breakthrough behavior. Analytical solutions developed for ion-exchange systems
      were able to provide accurate predictions for lysozyme breakthrough but not for
      ovalbumin. Impurities in the ovalbumin solutions used for the breakthrough
      experiments may have affected the ovalbumin uptake and led to the discrepancies
      between the predictions and the experimental results.

PMID- 21176839
TI  - Monolithic silica rod columns for high-efficiency reversed-phase liquid
      chromatography.
AB  - Chromatographic properties of a new type of monolithic silica rod columns were
      examined. Silica rod columns employed for the study were prepared from
      tetramethoxysilane, modified with octadecylsilyl moieties, and encased in a
      stainless-steel protective column with two polymer layers between the silica and
      the stainless-steel tubing. A 25 cm column provided up to 45,000 theoretical
      plates for aromatic hydrocarbons, or a minimum plate height of about 5.5 MUm, at
      optimum linear velocity of ca. 2.3 mm/s and back pressure of 7.5 MPa in an
      acetonitrile-water (80/20, v/v) mobile phase at 40 degrees C. The permeability of
      the column was similar to that of a column packed with 5 MUm particles, with K(F)
      about 2.4*10(-14) m(2) (based on the superficial linear velocity of the mobile
      phase), while the plate height value equivalent to that of a column packed with
      2.5 MUm particles. Generation of 80,000-120,000 theoretical plates was feasible
      with back pressure below 30 MPa by employing two or three 25 cm columns connected
      in series. The use of the long columns enabled facile generation of large numbers
      of theoretical plates in comparison with conventional monolithic silica columns
      or particulate columns. Kinetic plot analysis indicates that the monolithic
      columns operated at 30 MPa can provide faster separations than a column packed
      with totally porous 3-MUm particles operated at 40 MPa in a range where the
      number of theoretical plates (N) is greater than 50,000.

PMID- 21176840
TI  - A novel adsorbent for protein chromatography: supermacroporous monolithic cryogel
      embedded with Cu2+-attached sporopollenin particles.
AB  - The aim of this study is to prepare supermacroporous cryogels embedded with
      Cu(2+)-attached sporopollenin particles (Cu(2+)-ASP) having large surface area
      for high protein adsorption capacity. Supermacroporous poly(2-hydroxyethyl
      methacrylate) (PHEMA)-based monolithic cryogel column embedded with Cu(2+)-ASP
      was prepared by radical cryo-copolymerization of 2-hydroxyethyl methacrylate
      (HEMA) with N,N'-methylene-bis-acrylamide (MBAAm) as cross-linker directly in a
      plastic syringe for affinity purification of human serum albumin (HSA). Firstly,
      Cu(2+) ions were attached to sporopollenin particles (SP), then the
      supermacroporous PHEMA cryogel with embedded Cu(2+)-ASP was produced by free
      radical polymerization using N,N,N',N'-tetramethylene diamine (TEMED) and
      ammonium persulfate (APS) as initiator/activator pair in an ice bath. Embedded
      particles (10 mg) in PHEMA-based cryogel column were used in the
      adsorption/desorption of HSA from aqueous solutions. Optimum conditions of
      adsorption experiments were performed at pH 8.0 phosphate buffer, with flow rate
      of 0.5 mL/min, and at 5 degrees C. The maximum amount of HSA adsorption from
      aqueous solution was very high (677.4 mg/g SP) with initial concentration 6
      mg/mL. It was observed that HSA could be repeatedly adsorbed and desorbed to the
      embedded Cu(2+)-ASP in PHEMA cryogel without significant loss of adsorption
      capacity.

PMID- 21176841
TI  - Increased flow rate compatibility for universal acoustic flame detection in
      liquid chromatography.
AB  - The liquid chromatography (LC) flow rate tolerance of the universal Acoustic
      Flame Detector (AFD) is characterized and significantly expanded through using
      larger bore burners. For example, increasing the burner i.d. from 1.00 to 4.00 mm
      increases the AFD upper flow rate limit from 20 to 100 MUL/min. While signal and
      noise each reduce as the burner i.d. widens, the best current performance is
      obtained with a 2.30 mm i.d. burner. This approach also allows AFD operation over
      a broader range of mobile phase temperatures. As a result, the overall increased
      flow rate compatibility of the detector can facilitate improved chromatography
      and further development of LC-AFD applications.

PMID- 21176842
TI  - Editorial on "Chromatographic selectivity triangles" by Andrew R. Johnson and
      Mark F. Vitha.

PMID- 21176843
TI  - Internal standards: a source of analytical bias for volatile organic analyte
      determinations.
AB  - The use of internal standards in the determination of volatile organic compounds
      as described in SW-846 Method 8260C introduces a potential for bias in results
      once the internal standards (ISTDs) are added to a sample for analysis. The bias
      is relative to the dissimilarity between the analyte and internal standard
      physical properties that influence how easily analytes are separated from a
      matrix and concentrated during analysis. Method 5032 is a vacuum distillation
      procedure for extracting analytes from a sample for use with Method 8260C. Vacuum
      distillation is also incorporated within another GC/MS analytical procedure,
      Method 8261A. Method 8260C/5032 and Method 8261A are experimentally identical,
      however, Method 8261A uses internal standards differently by relating the
      recovery of each compound to its boiling point and relative volatility. By
      processing each analysis (water, soil, and biota) using both Method 8260C and
      Method 8261A, the two approaches are compared on the basis of analyte bias and
      the failure rate of the quality controls. Analytes were grouped by how similar
      their boiling points and natural log of their relative volatilities (lnRVs) were
      to their Method 8260C recommended ISTDs. For the most similar analytes, the
      Method 8260C determinations yielded an average bias less than 10% and a failure
      to meet calibration criteria less than 7%. However, as the difference between
      analyte and ISTD became greater the bias increased to over 40% (matrix dependent)
      and its calibration failure rate approached 70%. In comparison, when the Method
      8260C data were reprocessed as Method 8261A determinations, this trend for
      groupings was minimized with biases increasing from 6% to only 20% and the
      calibration failure rate went from 0% to 15%.

PMID- 21176844
TI  - Collagen and reticular fibers in left ventricular muscle in diabetic rats:
      physical exercise prevents its changes?
AB  - Diabetic cardiomyopathy contributes to the high incidence of mortality in both
      types of diabetes. We aimed to investigate the histochemical aspects of collagen
      and reticular fibers in the cardiac muscle and evaluate the influence of physical
      exercise on these aspects. Wistar rats were divided in 4 groups: sedentary
      control (SC), trained control (TC), sedentary diabetic (SD) and trained diabetic
      (TD). Diabetes was induced with alloxan (35 mg/kg). Training program consisted of
      swimming 1h/day with a load of 4.8% of body weight for TD and 5.2% for TC, during
      8 weeks. At the end of the experiment, samples of the left ventricle were
      collected, fixed in Bouin and processed on historesin. Sections were stained with
      periodic acid of Schiff, picrosirius-hematoxylin and ammoniacal silver. The PAS
      technique shows that individuals of group SD presented more intense reaction that
      the other groups. Picrosirius-hematoxylin technique showed a possible deposition
      of collagen fibers in SD. The TD group presented a reaction a lot similar to the
      controls' for both techniques', showing a possible prevention of this deposition.
      These results indicate that physical exercises might have an important role on
      the prevention of some negative alterations caused by experimental diabetes.

PMID- 21176845
TI  - The HIV-1 Nef protein has a dual role in T cell receptor signaling in infected
      CD4+ T lymphocytes.
AB  - The phenotypic changes that are induced by immune activation in CD4(+) T
      lymphocytes provide an optimal environment for efficient HIV-1 replication in
      these cells. The pathogenic Nef protein of HIV-1 modulates the T cell receptor
      (TCR) signaling, but whether this has a positive or negative effect on cellular
      activation is a matter of debate. Here we have investigated the response to TCR
      stimulation of primary CD4(+) T lymphocytes infected with wt or Nef-deficient HIV
      1. Results show that, in freshly isolated quiescent T cells, Nef superinduces
      NFAT and IL-2 production bypassing early TCR effector molecules. Conversely, the
      early phosphorylation of PLC-gamma1, the induction of NFAT, and the expression of
      IL-2 are impaired by Nef in sub-optimally activated/resting T cells. Our data
      indicate that Nef has a dual role in the modulation of TCR signaling aimed at
      favoring HIV-1 replication and spread in both quiescent and metabolically active
      CD4(+) T lymphocytes.

PMID- 21176846
TI  - The role of store-operated calcium influx in skeletal muscle signaling.
AB  - In cardiac and skeletal muscle Ca(2+) release from intracellular stores triggers
      actomyosin cross-bridge formation and the generation of contractile force. In the
      face of large fluctuations of intracellular calcium ([Ca(2+)](i)) that occur with
      contractile activity, myocytes are able to sense and respond to changes in
      workload and patterns of activation through calcium signaling pathways which
      modulate gene expression and cellular metabolism. Store-operated calcium influx
      has emerged as a mechanism by which calcium signaling pathways are activated in
      order to respond to the changing demands of the myocyte. Abnormalities of store
      operated calcium influx may contribute to maladaptive muscle remodeling in
      multiple disease states. The importance of store-operated calcium influx in
      muscle is confirmed in mice lacking STIM1 which die perinatally and in patients
      with mutations on STIM1 or Orai1 who exhibit a myopathy exhibited by hypotonia.
      In this review, we consider the role of store-operated Ca(2+) entry into skeletal
      muscle as a critical mediator of Ca(2+) dependent gene expression and how
      alterations in Ca(2+) influx may influence muscle development and disease.

PMID- 21176848
TI  - Reversible hair depigmentation in a patient treated with imatinib.

PMID- 21176847
TI  - The mechanism of agonist induced Ca2+ signalling in intact endothelial cells
      studied confocally in in situ arteries.
AB  - In endothelial cells there remain uncertainties in the details of how Ca(2+)
      signals are generated and maintained, especially in intact preparations. In
      particular the role of the sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA), in
      contributing to the components of agonist-induced signals is unclear. The aim of
      this work was to increase understanding of the detailed mechanism of Ca(2+)
      signalling in endothelial cells using real time confocal imaging of Fluo-4 loaded
      intact rat tail arteries in response to muscarinic stimulation. In particular we
      have focused on the role of SERCA, and its interplay with capacitative Ca(2+)
      entry (CCE) and ER Ca(2+) release and uptake. We have determined its contribution
      to the Ca(2+) signal and how it varies with different physiological stimuli,
      including single and repeated carbachol applications and brief and prolonged
      exposures. In agreement with previous work, carbachol stimulated a rise in
      intracellular Ca(2+) in the endothelial cells, consisting of a rapid initial
      phase, then a plateau upon which oscillations of Ca(2+) were superimposed,
      followed by a decline to basal Ca(2+) levels upon carbachol removal. Our data
      support the following conclusions: (i) the size (amplitude and duration) of the
      Ca(2+) spike and early oscillations are limited by SERCA activity, thus both are
      increased if SERCA is inhibited. (ii) SERCA activity is such that brief
      applications of carbachol do not trigger CCE, presumably because the fall in
      luminal Ca(2+) is not sufficient to trigger it. However, longer applications
      sufficient to deplete the ER or even partial SERCA inhibition stimulate CCE.
      (iii) Ca(2+) entry occurs via STIM-mediated CCE and SERCA contributes to the
      cessation of CCE. In conclusion our data show how SERCA function is crucial to
      shaping endothelial cell Ca signals and its dynamic interplay with both CCE and
      ER Ca releases.

PMID- 21176849
TI  - Very low mutation frequency of exons 5-9 in the CARD11 gene from 186 adult acute
      leukemia and 31 multiple myeloma samples.

PMID- 21176850
TI  - Detoxification and DNA repair genes polymorphisms and susceptibility of primary
      myelodysplastic syndromes in Chinese population.
AB  - Molecular epidemiological studies have found new insights into the etiology of
      myelodysplastic syndromes (MDS). We analyzed the polymorphisms of 5 genes in 275
      patients with primary MDS and 354 healthy controls in an attempt to identify
      candidate genetic risk factors for primary MDS in Chinese Han population. There
      was no difference in polymorphic variants of GSTM1, NQO1-C609T and XRCC3-C241T
      between the patients and controls. The homozygous variant C/C of RAD51-G135C was
      found to increase the susceptibility to MDS (OR, 4.13; p=0.001) and the risk of
      MDS association with structural abnormal karyotype (OR, 7.67; p=0.001). In
      addition, the null genotype of GSTT1 was correlated MDS patients with complex
      aberrant karyotype (OR, 3.25; p=0.012). These potential genetic predisposition
      suggested their possible involvement in the multistep pathogenesis of MDS.

PMID- 21176851
TI  - Epitope mapping of a PrP(Sc)-specific monoclonal antibody: identification of a
      novel C-terminally truncated prion fragment.
AB  - Monoclonal antibodies (mAbs) against prion proteins (PrPs) are indispensable in
      research and diagnosis of prion diseases, however the majority of these bind both
      the cellular (PrP(C)) and the disease-associated (PrP(Sc)) isoforms. According to
      the widely accepted protein-only hypothesis the two isoforms share the same
      sequence, but differ in their conformation. In the present study we set to
      determine the critical binding residues of our PrP(Sc)-specific mAbs with the
      view of discerning which residues play a key role in the conformational
      transition between PrP(C) and PrP(Sc). Focussing on the V5B2 mAb that provided
      differential labelling of prion-affected tissue from individuals positive for
      transmissible spongiform encephalopathies, we performed alanine scanning and
      phage-display epitope mapping to elucidate the antigenic determinants of this mAb
      and gain insight into its specificity on a molecular level. We observed that
      instead of discriminating between the two prion protein isoforms based on
      conformational differences, V5B2 binds a previously uncharacterized C-terminally
      truncated form of PrP(Sc) that ends with the residue Y226, which we named
      PrP226*. The addition of a single C-terminal amino-acid residue completely
      abolished V5B2 binding, while Western blots using recombinant full-length PrPs
      and PrPs terminating at Y226 confirmed that the V5B2 mAb discriminates between
      the two based on their difference in length.

PMID- 21176852
TI  - Molecular identification of duck and quail common cytokine receptor gamma chain
      genes.
AB  - Common cytokine receptor gamma chain (gamma(c)) family cytokines play crucial
      roles in the regulation of innate and adaptive immune responses. Unlike mammals,
      chickens possess two different gamma(c) transcripts. To determine if this
      difference is present in other avian species, gamma(c) cDNA and genomic clones
      from ducks and quails were investigated. Two different gamma(c) transcripts were
      identified in both species and designated as duck gamma(c)-a (dugamma(c)-a),
      dugamma(c)-b, quail gamma(c)-a (qugamma(c)-a), and qugamma(c)-b. Comparisons
      between the duck and quail gamma(c) cDNA and genomic sequences indicated that the
      two transcripts were produced by alternative splicing. Unexpectedly, the
      dugamma(c)-b contained the fifth intron, a frame-switching 88-bp insertion,
      resulting in a receptor molecule lacking a transmembrane region. These findings
      indicate a possibility that avian species, unlike mammals, express two different
      gamma(c) transcripts due to alternative splicing. This study is the first
      demonstration of an alternatively spliced gamma(c) isoform that lacks a
      transmembrane domain.

PMID- 21176853
TI  - Myocardial delayed enhancement in paucisymptomatic nonischemic dilated
      cardiomyopathy.
AB  - OBJECTIVES: We investigated the prognostic role of myocardial fibrosis by delayed
      enhancement (DE) cardiovascular magnetic resonance (CMR) in nonischemic dilated
      cardiomyopathy (NICM) patients with no or mild symptoms of heart failure (HF).
      METHODS: A prospective cohort of 125 NICM patients (82 males, age 59+/-14years,
      mean+/-SD) with echocardiographic evidence of left ventricular (LV) systolic
      dysfunction (mean ejection-fraction 33+/-10%), without (stage B) or with history
      of mild HF symptoms (stage C, NYHA classes I-II) was enrolled. The end-point was
      a composite of cardiac death and HF hospitalization. RESULTS: Fifty (40%)
      patients showed myocardial DE, representing 12+/-7% of LV mass. During a median
      follow-up of 14.2months, 16 (32%) patients with DE experienced a composite event
      versus only 6 (8%) patients without DE (Kaplan-Meier survival curve, p=0.001).
      After correction for age, CMR-derived LV and right ventricular volumes,
      echocardiographic measurements of LV diastolic function and Doppler-estimated
      systolic pulmonary artery pressure, the presence of DE remained a strong and
      independent predictor of cardiac death or HF hospitalization (hazard ratio: 5.32,
      95% confidence intervals 1.60 to 17.63, p=0.006). CONCLUSIONS: In NICM patients
      with no or mild HF symptoms, the presence of myocardial DE is a strong predictor
      of worse clinical outcome even after correction for other established prognostic
      determinants. Contrast-enhanced CMR may be useful in prognostic stratification
      from the early stages of NICM.

PMID- 21176854
TI  - Efficacy of the Boar-Operated-System to deliver baits to feral swine.
AB  - Feral swine (Sus scrofa) pose a significant disease threat to livestock and
      humans. Emerging technologies to reduce feral swine disease transmission risks
      include fertility control, vaccination, and toxicants. However, for these
      technologies to be appropriate for field application, a feral swine-specific oral
      delivery system is needed. We used two field trials to generate information
      related to appropriate field application of the Boar-Operated-System (BOSTM), an
      oral delivery system designed to provide bait access only to feral swine. Our
      objectives were to determine whether pre-baiting BOSTM units increased bait
      removal and to evaluate the proportion of feral swine and non-target animals that
      ingest baits designed to deliver pharmaceuticals through the BOSTM. During both
      trials we used baits housed within 10 BOSTM units. We monitored wildlife
      visitation, bait removal, and ingestion using motion sensing digital photography
      and baits containing the bait marker tetracycline hydrochloride (TH). During
      trial 1 we found three of five pre-baited BOSTM units were used by feral swine
      only. Additionally, we found the five BOSTM units that were not pre-baited were
      not used by feral swine or non-target wildlife. During trial 2 we determined bait
      removal from the BOSTM to be reduced by only 10% for feral swine when activated,
      whereas bait removal from the BOSTM by all other wildlife was reduced by 100%
      when activated. We captured 81 feral swine and 23 raccoons and found 90% and 13%
      to have TH-marked teeth, respectively. With minor modifications, the BOSTM should
      be considered a valuable tool to be used in feral swine disease management in
      conjunction with existing technologies.

PMID- 21176855
TI  - Risk factors for Listeria monocytogenes contamination in French laying hens and
      broiler flocks.
AB  - The objective of this study was to identify potential risk factors for Listeria
      monocytogenes contamination in French poultry production. Eighty-four flocks of
      layer hens kept in cages and 142 broiler flocks were included in this study. For
      each production type, a questionnaire was submitted to farmers and fecal samples
      were taken to assess the L. monocytogenes status of the flocks during a single
      visit to the farm. Two logistic regression models (specific to each production)
      were used to assess the association between management practices and the risk of
      L. monocytogenes contamination of the flock. The prevalence of L. monocytogenes
      positive flocks was 30.9% (95% CI: 21.0; 40.9) and 31.7% (95% CI: 24.0; 39.4) for
      cage-layers and broiler flocks, respectively. For layer flocks, the risk of L.
      monocytogenes contamination was increased when pets were present on the
      production site. When droppings were evacuated by conveyor belt with deep pit
      storage, the risk of L. monocytogenes contamination decreased significantly. Feed
      meal was found to be associated with a higher risk of L. monocytogenes
      contamination than feed crumb. For broiler flocks, the risk of L. monocytogenes
      contamination was increased when farmers did not respect the principle of two
      areas (clean and dirty) at the poultry house entrance. A first disinfection by
      thermal fogging and the absence of pest control of the poultry house before the
      arrival of the next flock was found to increase the risk of contamination. When
      litter was not protected during storage and when farm staff also took care of
      other broiler chicken houses, the risk of L. monocytogenes contamination
      increased significantly. In the case of the watering system, nipples with cups
      were found to decrease the risk of contamination.

PMID- 21176856
TI  - Extended MLST-based population genetics and phylogeny of Vibrio parahaemolyticus
      with high levels of recombination.
AB  - A collection of 174 global isolates of Vibrio parahaemolyticus were analyzed by
      multilocus sequence typing (MLST) on the basis of ten conserved genes. The
      results showed a high level of nucleotide and allelic diversity with the evidence
      of purifying selection and of frequent recombination. Recombination played a much
      greater role than mutation in generating genetic heterogeneity. The 174 strains
      could be assigned into 89 different sequence types, which could be further
      separated into six clonal complexes (CCs; CC1 to CC6) plus 71 singletons. The
      three major CCs, namely CC1 to CC3, corresponded to the groups of pre-1996
      clinical old-O3:K6 strains (trh(+), T3SS2beta(+), tdh(-), T3SS2alpha(-), and GS
      PCR(-)), post-1996 pandemic strains (trh(-), T3SS2beta(-), tdh(+), T3SS2alpha(+),
      and GS-PCR(+)) and non-clinical isolates (trh(-), T3SS2beta(-), tdh(-),
      T3SS2alpha(-), and GS-PCR(-)), respectively. The MLST data enable the
      construction of a phylogenetic structure from the allelic profiles rather the
      nucleotide sequences, so as to reduce the affect of frequent recombination. The
      six CCs arose on a background of mutation and recombination, and according to the
      previously reported data, this bacterium could be evolved fast due to lateral
      acquisition of foreign genes especially including those encoding virulence
      determinants. V. parahaemolyticus had a typical epidemic population structure
      that is driven by mutation, recombination and lateral gene transfer.

PMID- 21176857
TI  - The relationship between adipocyte fatty acid binding protein-4, retinol binding
      protein-4 levels and early diabetic nephropathy in patients with type 2 diabetes.
AB  - Adipocyte fatty acid binding protein-4 (A-FABP4) and retinol binding protein-4
      (RBP4) have recently been linked to type 2 diabetes mellitus (DM). Serum A-FABP4
      and RBP4 levels and their relationships with early diabetic nephropathy were
      examined in 87 type 2 diabetic patients. The patients with diabetic nephropathy
      showed high A-FABP4 levels compared to the patients without diabetic nephropathy
      (p=0.0001). Log A-FABP4 correlated positively with age (p=0.02), log duration of
      diabetes (p=0.04), log body mass index (BMI) (p=0.0001), log creatinine
      (p=0.007), log C-reactive protein (CRP) (p=0.01), log albumin excretion rate
      (AER) (p=0.001), and negatively with MDRD-GFR (p=0.0001). Serum RBP4 levels were
      similar between the patients with and without diabetic nephropathy. RBP4
      correlated positively with triglycerides (p=0.001), log creatinine (p=0.009), and
      negatively with MDRD-GFR (p=0.04). In regression analysis, log A-FABP4 was
      associated with age, sex, log BMI, and log AER (r(2)=0.43) and RBP4 was
      associated with triglycerides and log creatinine (r(2)=0.22). In conclusion, we
      found high serum A-FABP4 but unchanged RBP4 concentrations and their associations
      with renal function and early diabetic nephropathy in type 2 DM.

PMID- 21176858
TI  - PPARgamma-dependent peptidoglycan recognition protein 3 (PGlyRP3) expression
      regulates proinflammatory cytokines by microbial and dietary fatty acids.
AB  - PGlyRPs recognize bacterial peptidoglycan and function in antibacterial innate
      immunity. Focusing on the interference between nutrition and recognition pattern
      proteins, free fatty acids (FFA) of dietary and bacterial sources may exert their
      immunological response through modulating the expression level of the PGlyRPs in
      enterocytes. PGlyRP3 was the only PGlyRPs member expressed in Caco2 cells. In
      silico analysis showed that the promoter of PGlyRP3 has some PPRE regions that,
      as tested by EMSA, bind physically to the PPARgamma-RXRalpha complex. PGlyRP3
      gene expression was induced by PPARgamma ligands including GW1929 and some FFA.
      Overexpression of PGlyRP3 in Caco2 cells down regulated the expression of the
      inflammatory cytokines IL-8, IL-12 and TNF-alpha, while its silencing increased
      the expression of these cytokines. FFA that induced the PGlyRP3 inhibited the
      tested cytokines. Silencing of PGlyRP3 gene caused the same FFA to increase the
      cytokine gene expression. A negative regulation of NF-kappaB pathway, including
      up-regulation of Ikappabeta-alpha and down regulation of NF-kappaB and COX-2, is
      involved in the anti-inflammatory effects of PGlyRP3. In conclusion, PPARgamma
      mediates a modulation of PGlyRP3 gene expression, which is involved in inhibiting
      inflammation through negative regulation of NF-kappaB pathway.

PMID- 21176859
TI  - Nurses' Internet self-efficacy and attitudes toward web-based continuing
      learning.
AB  - OBJECTIVE: There are increasing opportunities for nurses to engage in continuing
      learning via the Internet; hence, it is important to explore nurses' attitudes
      toward web-based continuing learning. METHOD: This paper explores 267 Taiwanese
      clinical nurses' attitudes toward web-based continuing learning. In addition, the
      role of the nurses' Internet self-efficacy in their attitudes is investigated.
      This study utilizes two questionnaires to respectively survey the nurses'
      Internet self-efficacy and their attitudes toward web-based continuing learning.
      In particular, the Internet Self-efficacy Survey includes two scales: 'Basic self
      efficacy' (the perceived confidence of using basic Internet functions, such as
      the confidence in using a web browser or searching for online information) and
      'Advanced self-efficacy' (the perceived confidence of using advanced Internet
      functions, such as the confidence in online discussion or making online
      payments). RESULTS AND FINDINGS: Exploratory factor analyses indicated adequate
      reliability and validity of the two questionnaires. The regression analyses
      revealed that both nurses' basic and advanced Internet self-efficacy can
      positively explain the perceived usefulness, ease of use and friendly feeling
      when using web-based continuing learning environments, whereas nurses' advanced
      Internet self-efficacy was the only predictor to explain how they intend to use
      web-based continuing learning environments more.

PMID- 21176860
TI  - Novel methods for 3D postoperative analysis of total knee arthroplasty using 2D
      3D image registration.
AB  - BACKGROUND: Radiographic evaluation of patients after total knee arthroplasty is
      an important tool for assessing the correct position of the implants and the axis
      of limb alignment because this will determine long-term durability of the
      implants. Recently, 2D-3D medical image registration methods are developed for 3D
      postoperative analysis of total knee arthroplasty. However, most of these
      techniques have focused only on knee implants. METHODS: A 2D-3D medical image
      registration is implemented to compute the 3D positions of not only implants but
      also lower limb bones. The following 3D postoperative analysis methods for total
      knee arthroplasty are presented in this paper: (1) automatic calculation of
      relative angles of implants and bones, (2) assessment of external rotation angles
      of inserted implants, and (3) measurement and comparison of both flexion
      extension gap balances. Finally these methods have been applied in five patients
      who underwent total knee replacements. FINDINGS: A practical method that can
      evaluate the patient's knee conditions has been successfully developed. The
      repeatability and accuracy of 2D-3D registration were around 0.2mm as obtained
      from the tests using model bones. Based on the 3D information, the novel methods
      of postoperative analysis were proposed and successfully applied to the patients.
      INTERPRETATION: The 3D positions for both knee implants and lower limb bones can
      be calculated in order to perform comprehensive postoperative analyses of total
      knee arthroplasty. The proposed analyses of the postoperative evaluations
      facilitated various 3D evaluations of the status of implants, alignment of lower
      limb and gap balances which were not previously feasible.

PMID- 21176861
TI  - Characterization and application of Ti-containing mesoporous silica for dye
      removal with synergistic effect of coupled adsorption and photocatalytic
      oxidation.
AB  - Highly ordered mesoporous silica, Santa Barbara Amorphous-15 (SBA-15), and
      titanium-substituted mesoporous silica (TiSBA-15) materials were successfully
      synthesized, characterized, and evaluated. The textual and structural properties
      of the prepared materials with various titanium contents were characterized by
      inductively coupled plasma-mass spectrometer (ICP-MS), powder X-ray diffraction
      (XRD) patterns, nitrogen physisorption isotherms, scanning electron microscopy
      (SEM), and transmission electron microscopy (TEM). A limited content of titanium
      could be effectively substituted into the framework of SBA-15 without provoking
      structure change. The adsorptive performance was examined by methylene blue (MB)
      adsorbed on prepared materials. The isotherm models were analyzed to describe the
      adsorption behavior of prepared materials. The adsorption isotherms were well
      fitted with Langmuir and Freundlich models in the simulation of the adsorption
      behavior of dyes. The SBA-15 and TiSBA-15 materials were found to be effective
      adsorbents for MB from aqueous solutions. The photodegradation of MB and total
      organic carbon (TOC) analysis on solid composites were used to evaluate the
      catalytical performance of Ti-containing mesoporous silica. The synergistic
      effect of adsorptive and photocatalytical ability of prepared TiSBA-15 was
      identified. The regeneration and cyclic performance were also proved. These
      results revealed that TiSBA-15 could be one effective alternative material for
      dye removal.

PMID- 21176862
TI  - Enhanced dissipation of PAHs from soil using mycorrhizal ryegrass and PAH
      degrading bacteria.
AB  - The major aim of this experiment was to test the effects of a multi-component
      bioremediation system consisting of ryegrass (Lolium multiflorum), polycyclic
      aromatic hydrocarbons (PAHs)-degrading bacteria (Acinetobacter sp.), and
      arbuscular mycorrhizal fungi (Glomus mosseae) for cleaning up PAHs contaminated
      soil. Higher dissipation rates were observed in combination treatments: i.e.,
      bacteria+ryegrass (BR), mycorrhizae+ryegrass (MR), and
      bacteria+mycorrhizae+ryegrass (BMR); than bacteria (B) and ryegrass (R) alone.
      The growth of ryegrass significantly (p<0.05) increased soil peroxidase
      activities, leading to enhanced dissipation of phenanthrene (PHE) and pyrene
      (PYR) from soil. Interactions between ryegrass with the two microbes further
      enhanced the dissipation of PHE and PYR. Mycorrhizal ryegrass (MR) significantly
      enhanced the dissipation of PYR from soil, PYR accumulation by ryegrass roots and
      soil peroxidase activities under lower PHE and PYR levels (0 and 50+50 mg kg(
      1)). The present results highlighted the contribution of mycorrhiza and PAH
      degrading bacteria in phytoremediation of PAH contaminated soil, however more
      detailed studies are needed.

PMID- 21176863
TI  - The effect of clay treatment on remediation of diethylketone contaminated
      wastewater: uptake, equilibrium and kinetic studies.
AB  - The ability of four different clays to adsorb diethylketone was investigated in
      batch experiments aiming to treat wastewater with low solvent concentrations. The
      adsorption performance in terms of uptake followed the sequence:
      vermiculite>sepiolite=kaolinite=bentonite, for all the adsorbent doses tested
      (from 0.1 to 1.5 g) in 150 mL of ketone solution (800 mg/L). The equilibrium data
      in the batch systems were described by Sips and Dubinin-Raduskevich isotherms.
      The best fits for bentonite and kaolinite clays were obtained with the Sips
      isotherm and for sepiolite and vermiculite the best fits were obtained with the
      Dubinin-Raduskevich model. Kinetic data were described by pseudo-first and pseudo
      second order kinetics models. The best fit was obtained for the pseudo-first
      order model which assumed that the interaction rate was limited only by one
      process or mechanism on a single class of sorbing sites and that all sites were
      time dependent. The presence of functional groups on the clay surface that might
      have interacted with the solvent was confirmed by FTIR. XRD analysis was also
      performed. This study showed that the tested clays are very effective for the
      removal of diethylketone from industrial effluents.

PMID- 21176864
TI  - Relative condition factor and parasitism in anostomid fishes from the floodplain
      of the Upper Parana River, Brazil.
AB  - Individuals of four species of Leporinus were captured in the floodplain of the
      Upper Parana River and their metazoan parasites were collected. Fifty-eight taxa
      of ectoparasites and endoparasites were recorded: 31 in Leporinus lacustris, 32
      in Leporinus friderici, 28 in Leporinus obtusidens and 25 in Leporinus elongatus.
      The aim of this paper was to study the relationship between the host's condition
      and the parameters of infrapopulations and infracommunities. The health of the
      host was represented by the relative condition factor (Kn). Richness and number
      of individuals in the infracommunities of ectoparasites covariated with the Kn of
      the hosts in one species of fish. Some infrapopulations of ectoparasites
      covariated negatively and/or the mean Kn of parasitized individuals was lower
      than those without parasites. The abundance in some infrapopulations of
      endoparasites covariated positively with the Kn and/or the mean Kn of parasitized
      fish was better. These results may be related to different transmission
      strategies used by ecto and endoparasites.

PMID- 21176865
TI  - Evaluation of three novel azasterols against Toxoplasma gondii.
AB  - Previous studies from our group have demonstrated the high susceptibility of
      Toxoplasma gondii tachyzoites to the sterol analogues 22,26-azasterol and 24,25
      (R,S)-epiminolanosterol. In this work we present data on testing in vitro three
      novel azasterols as potential agents for the treatment of toxoplasmosis. The
      three compounds inhibited parasite growth at micromolar concentrations, in a dose
      dependent manner. Electron microscopy analysis of intracellular tachyzoites after
      treatment with the most effective compound showed drastic mitochondrion swelling
      associated with the appearance of an electron-lucent matrix and disrupted
      cristae. Parasite lysis also took place. The appearance of electron dense
      cytoplasmic structures similar to amylopectin granules distributed throughout the
      parasite suggests that azasterols might be inducing differentiation of those
      tachyzoites which were not lysed to the bradyzoite stage.

PMID- 21176866
TI  - Pathology of the swine-origin influenza A (H1N1) flu.
AB  - Pathological studies would aid in finding the real causes of death and in
      outlining adequate strategies for treatment regarding patients with poor clinical
      outcome of influenza A H1N1 swine flu. We describe the autopsy findings of six
      cases of influenza A H1N1 swine flu. The lungs in these cases had an alveolitis
      with hyaline membranes. Immunohistochemistry for influenza was positive only in
      lungs (in pneumocytes, in macrophages, in some multinucleate cells in alveoli,
      and in blood vessel walls) of two cases. Disseminated petechial brain hemorrhage
      was observed in four of the cases and focally in one case. Focal myocarditis was
      observed in one case. Coagulation infarcts (ischemic) were observed in the
      pancreas of two cases and in the spleen of two cases. Our results indicate that
      there was marked replication of the virus in alveoli in the more recently
      infected cases, which could explain the extensive diffuse alveolar damage. In our
      cases, there were important vascular phenomena that resulted in hemorrhage and
      thrombosis, but without marked decrease of platelet count and coagulation cascade
      disruptions. This would be attributed to hemodynamic disruption. However, it is
      possible that the hemorrhagic petechial lesions in the brain are due to vascular
      lesions or to an increase of endothelial permeability.

PMID- 21176867
TI  - Synchronization of oestrus and ovulation by short time combined FGA, PGF(2alpha),
      GnRH, eCG treatments for natural service or AI fixed-time.
AB  - Two experiments were conducted in ewes in order to develop an oestrus-ovulation
      short time synchronization protocol based on combined FGA, PGF(2alpha), GnRH, eCG
      treatments, for use in dairy sheep before natural service (Experiment 1) or for
      fixed-time artificial insemination (Experiment 2), during the breeding season. In
      Experiment 1 seventy-five non-lactating dairy ewes were subdivided into 5
      treatment groups (N=15): (1) Group Fe - control, which received FGA vaginal
      sponges (14 days)+eCG (Day 14); (2) Group FPe, FGA (5 days)+PGF(2alpha) (Day
      5)+eCG (Day 5); (3) Group PFe, PGF(2alpha) (Day 0)+FGA (5 days)+eCG (Day 5); (4)
      Group PFG, PGF(2alpha) (Day 0)+FGA (5 days)+GnRH (30h after sponge removal,
      s.r.); (5) Group GPe, GnRH (Day 0)+PGF(2alpha) (Day 5)+eCG (Day 5). Ewes were
      checked for oestrus and hand-mated. Time of ovulation was recorded by laparoscopy
      for 10 animals from each treatment. The percentages of female in oestrus and the
      interval to oestrus (h after treatment), fertility and prolificacy rate were
      recorded. There were no treatment differences in the percentage of females in
      oestrus. The interval to oestrus was earlier in Fe Group and delayed in FPe Group
      (P<0.01). Ovulation time was earlier in GPe Group compared to FPe Group (P<0.05).
      Fertility rates were significantly different (P<0.05) between the PFe and the
      FPeG Groups compared with the PFG Group. No significant differences were observed
      in prolificacy among the treatments. In Experiment 2, sixty dry ewes were
      subdivided (N=20) into the following three experimental treatment groups: (1)
      Group FP, FGA (5 days)+PGF(2alpha) (Day 5); (2) Group FPG, FGA (5
      days)+PGF(2alpha) (Day 5)+GnRH (30hs.r.); (3) Group FPeG, FGA (5
      days)+PGF(2alpha) (Day 5)+eCG (Day 5)+GnRH (30hs.r.). These were further
      subdivided into two groups (N=10) corresponding to 52 and 60hs.r. fixed-time
      insemination. Laparoscopic intrauterine insemination was performed with frozen
      semen (80*10(6)spermatozoa/dose) and ovulation time was recorded in a subgroup
      (N=10). GnRH resulted in an earlier ovulation time (P<0.05) in FPG and FPeG
      Groups (53.0h vs 61.6h). Fertility rate was higher in FPeG treated ewes
      inseminated at 60hs.r. (60%, 6/10). In FP and FPG Groups fertility rates were
      higher following insemination at 52hs.r. (50.0 and 40.0%).

PMID- 21176868
TI  - HPLC-MS/MS methods for the quantitative analysis of ophthalmic acid in rodent
      plasma and hepatic cell line culture medium.
AB  - Ophthalmic acid (OA), an endogenous tripeptide analogue of glutathione, has been
      suggested as a potential biomarker for paracetamol/acetaminophen hepatotoxicity.
      Here HPLC-MS/MS methods have been developed for the precise, sensitive and
      specific detection and quantification of OA in in vitro cell culture medium and
      plasma. For the cell culture medium the LLOQ was found to be 1 ng/ml, with less
      than 1% between sample carry over at all concentrations and precision below 15%
      for within day and below 9% for between day analyses. For rat plasma the presence
      of endogenous OA resulted in the LLOQ being 25 ng/ml (defined as the lowest
      concentration on the calibration curve where the base peak was less than 20% of
      the LLOQ). For the plasma assay the percentage carry over was less than 1% for
      all concentrations and within and between batch precision was below 21%. The
      methods were linear for both sample types from the LLOQ up to 5 MUg/ml. The
      method was successfully applied to the determination of OA in samples obtained
      following the chronic administration of the rat hepatotoxin methapyrilene, where
      plasma OA concentrations were observed to show a weak negative correlation with
      those of established liver injury biomarkers such as aspartate aminotransferase
      (AST).

PMID- 21176869
TI  - Use of differential reinforcement to reduce behavior problems in adults with
      intellectual disabilities: a methodological review.
AB  - The least-restrictive-alternative guideline for providing treatment emphasizes
      the use of non-aversive procedures to reduce maladaptive behaviors in individuals
      with intellectual disability (ID). Differential reinforcement (DR) is an
      excellent example of such a non-aversive, reinforcement based behavioral
      intervention. The purpose of this literature review was to summarize and provide
      a methodological analysis of studies, conducted between 1980 and 2009, using a DR
      contingency to reduce problem behaviors in adults with ID. A total of 31 studies
      were located that met the inclusion criteria. Of these, 15 reported DR to be an
      effective intervention when used independently. Of the remaining, 10 studies
      found DR to be useful as part of a treatment package, and six found a DR
      contingency used independently to be ineffective, and only observed treatment
      effects when an aversive component was added. Very few studies assessed the use
      of DR in older adults and in individuals with mild ID; these reflect areas of
      future research. A methodological analysis found that several studies did not
      report information on key methodological variables; for example, conducting a
      functional analysis and a stimulus preference assessment to guide choice of
      treatment and reinforcers, thinning very dense DR schedules, assessing collateral
      behaviors, generalization of behavior change across settings and implementers,
      and following up treatment outcomes over time. The overall positive findings
      about the effectiveness of DR are encouraging; however, more methodologically
      robust studies would serve to make such findings more conclusive and practically
      relevant for implementation in natural settings for adults with ID.

PMID- 21176870
TI  - Piezosurgery in oral and maxillofacial surgery.
AB  - This review summarizes current knowledge and experience with piezosurgery, a
      promising, meticulous and soft tissue-sparing system for bone cutting, based on
      ultrasonic microvibrations. The main advantages of piezosurgery include soft
      tissue protection, optimal visibility in the surgical field, decreased blood
      loss, less vibration and noise, increased comfort for the patient and protection
      of tooth structure. To date it has been indicationed for use in oral and
      maxillofacial surgery, otorhinolaryngology, neurosurgery, ophthalmology,
      traumatology and orthopaedics. The main indications in oral surgery are sinus
      lift, bone graft harvesting, osteogenic distraction, ridge expansion, endodontic
      surgery, periodontal surgery, inferior alveolar nerve decompression, cyst
      removal, dental extraction and impacted tooth removal. In conclusion,
      piezosurgery is a promising technical modality for different aspects of bone
      surgery with a rapidly increasing number of indications throughout the whole
      field of surgery.

PMID- 21176871
TI  - FAP-1 and NF-kappaB expressions in oral squamous cell carcinoma as potential
      markers for chemo-radio sensitivity and prognosis.
AB  - This study was designed to investigate the feasibility of using Fas-associated
      phosphatase-1 (FAP-1), nuclear factor kappa B (NF-kappaB) and p53 as markers for
      chemo-radio sensitivity in oral squamous cell carcinoma (OSCC). FAP-1 plays a
      role as an anti-apoptotic factor through Fas-dependent apoptosis after chemo
      radiotherapy. NF-kappaB and p53 might be involved in modulation of FAP-1
      expression. FAP-1, NF-kappaB and p53 expression were immunohistochemically
      examined using biopsy specimens in 50 OSCC patients treated with chemotherapy
      and/or radiotherapy. FAP-1 was expressed in 52%, NF-kappaB in 52% and p53 in 46%
      of patients. There was no significant difference in FAP-1, p53 or NF-kappaB
      expression according to the clinicopathological features. No correlation was
      found among FAP-1, p53 or NF-kappaB expression. FAP-1-positive cases showed a
      poorer survival rate than FAP-1-negative cases (P = 0.0409) and NF-kappaB
      positive cases showed a poorer survival rate than NF-kappaB-negative cases (P =
      0.0018). Multivariate analysis showed that FAP-1 expression, NF-kappaB
      expression, clinical stage and age were significant independent variables for
      survival (clinical stage: P = 0.0016; age: P = 0.0016; NF-kappaB: P = 0.0314; FAP
      1: P = 0.0366). These results suggest that FAP-1 and NF-kappaB might play a role
      as chemo-radioresistant factor during chemo-radiotherapy, and FAP-1 and NF-kappaB
      expression in OSCC would be feasible markers for chemo-radio sensitivity and
      prognosis.

PMID- 21176872
TI  - Kaposi's sarcoma and human dermal microvascular endothelial cells infected with
      Kaposi's sarcoma-associated herpesvirus express CCL21.

PMID- 21176873
TI  - Modulation of semaphorin 3A expression by calcium concentration and histamine in
      human keratinocytes and fibroblasts.
AB  - BACKGROUND: Both neurotrophins and chemorepellents are involved in the elongation
      and sprouting of itch-associated C-fibers in the skin. Nerve growth factor (NGF)
      and semaphorin 3A (Sema3A) are representatives of these two types of axon
      guidance factors, respectively. OBJECTIVE: We investigated the effects of calcium
      concentration and histamine on the expression of NGF and Sema3A in normal human
      epidermal keratinocytes (NHEK) and normal human fibroblasts (NHFb). METHODS: NHEK
      and NHFb were cultured under different calcium concentrations (0.15-0.9 mM) with
      or without histamine, and the expression of mRNA for NGF and SEMA3A was assessed
      by real-time PCR analysis. An immunohistochemical study was performed for Sema3A
      using normal skin and skin cancer specimens. RESULTS: In NHEK, SEMA3A expression
      was elevated by high calcium concentration and reduced by low calcium condition,
      while NGF expression was not dependent on calcium. Their expressions were
      unchanged by calcium in NHFb. Immunohistochemically, keratinocytes in the prickle
      layer of normal epidermis and squamous cell carcinoma cells were positive for
      Sema3A, sparing basal cells and suprabasal cells. The addition of histamine to
      NHEK at 10 MUg/ml enhanced SEMA3A expression but depressed NGF expression. In
      NHFb, however, histamine decreased both NGF and SEMA3A levels. CONCLUSIONS:
      Sema3A inhibits C-fiber elongation/sprouting in the upper layers of the
      epidermis, where calcium concentration is high, thereby determining the nerve
      endings. Histamine reduces Sema3A production by fibroblasts, allowing C-fibers to
      elongate in the dermis. In contrast, the histamine-augmented keratinocyte
      production of Sema3A might suppress C-fiber elongation and exaggerated pruritus.

PMID- 21176874
TI  - Comment on: 'Rabies and African bat lyssavirus encephalitis and its prevention'.

PMID- 21176875
TI  - Synthesis and characterization of enzyme-magnetic nanoparticle complexes: effect
      of size on activity and recovery.
AB  - The influence of particle size on the activity and recycling capabilities of
      enzyme conjugated magnetic nanoparticles was studied. Co-precipitation and
      oxidation of Fe(OH)(2) methods were used to fabricate three different sizes of
      magnetic nanoparticles (5 nm, 26 nm and 51 nm). Glucose oxidase was covalently
      bound to the magnetic nanoparticles by modifying the surfaces with 3
      (aminopropyl)triethoxysilane (APTES) and a common protein crosslinking agent,
      glutaraldehyde. Analysis by Transmission Electron Microscopy (TEM) showed that
      the morphology of the magnetic nanoparticles to be spherical and sizes agreed
      with results of the Brunauer, Emmett, and Teller (BET) method. Magnetic strength
      of the nanoparticles was analyzed by magnetometry and found to be 49 emu g(-1) (5
      nm), 73 emu g(-1) (26 nm), and 85 emu g(-1) (51 nm). X-ray photoelectron
      spectroscopy (XPS) confirmed each step of the magnetic nanoparticle surface
      modification and successful glucose oxidase binding. The immobilized enzymes
      retained 15-23% of the native GOx activity. Recycling stability studies showed
      approximately 20% of activity loss for the large (51 nm) and medium (26 nm) size
      glucose oxidase-magnetic nanoparticle (GOx-MNP) bioconjugate and about 96%
      activity loss for the smallest GOx-MNP bioconjugate (5 nm) after ten cycles. The
      bioconjugates demonstrated equivalent total product conversions as a single
      reaction of an equivalent amount of the native enzyme after the 5th cycle for the
      26 nm nanoparticles and the 7th cycle for the 51 nm nanoparticles.

PMID- 21176876
TI  - Development and in vitro evaluation of deacety mycoepoxydiene nanosuspension.
AB  - Deacety mycoepoxydiene (DM), extracted from Phomopsis sp. A123 of
      thalassiomycetes, is a novel and potent anti-cancer agent. Due to its
      physicochemical characteristics, the drug, a poorly water-soluble weak acid,
      shows poor solubility and dissolution characteristics. To improve the solubility
      and dissolution, formulation of DM as nanosuspension has been performed in this
      study. Nanosuspensions were developed by high-pressure homogenization (HPH)
      (DissoCubes((r)) Technology) and transformed into dry powder by freeze-drying.
      The nanosuspension produced was then investigated using optical microscope,
      photon correlation spectroscopy (PCS), zeta potential measurement, SEM, TEM, AFM,
      DSC and XRD. To verify the theoretical hypothesis on the benefit of increased
      surface area, in vitro saturation solubility and dissolution profile were
      investigated. In addition, the in vitro cell cytotoxicity was examined. Results
      showed that a narrow size distributed nanosuspension composed of unchanged
      crystalline state with a mean particle size of 515+/-18 nm, a polydispersity
      index of 0.12+/-0.03 and a zeta potential of -23.1+/-3.5 mV was obtained. In the
      in vitro dissolution test an accelerated dissolution velocity and increased
      saturation solubility could be shown for the MD nanosuspension. The in vitro
      cytotoxicity experiments provided evidence for an enhanced efficacy of the DM
      nanosuspension formulation compared to free DM solution. Taken together, these
      results illustrate the opportunity to formulate DM in nanosuspension form as an
      anti-prostate cancer delivery system.

PMID- 21176877
TI  - Assembly of dandelion-like Au/PANI nanocomposites and their application as SERS
      nanosensors.
AB  - The monodisperse, uniform dandelion-like Au/polyaniline (PANI) composite
      nanospheres were synthesized by a simple one-step process without any additives
      or templates. The nanospheres are really composed of many short nanorods and the
      average diameter of whole nanospheres is about 180 nm. The morphology of Au/PANI
      composites could be controlled by adjusting the molar ratio of HAuCl(4) to
      aniline. The prepared nanocomposite is developed as a wonderful sensor for the
      detection of Hg(2+) ions, which is based upon the Raman intensity response of
      PANI to Hg(2+) ions. Results from the morphology-dependent sensitivity
      investigations show that the dandelion-like nanospheres have an ultra sensitive
      response (as low as 10(-11)M) compared with other morphologies. The nanosensor
      also exhibits good reproducibility and greater selectivity for Hg(2+) ions than
      the other heavy metal ions. And the mechanism was proposed. The proposed
      nanosensors can be applied for highly sensitive and selective chemical analysis
      in a variety of environmental detection.

PMID- 21176879
TI  - Over rough and smooth: amputee gait on an irregular surface.
AB  - When negotiating irregular surfaces, the control of dynamic stability is
      challenged. In this study, we compared the adjustments in stepping behaviour and
      arm-swing of 18 unilateral transtibial amputees and 17 able-bodied participants
      when walking on flat and irregular surfaces. Experimental findings revealed that
      unilateral transtibial amputees reduced their gait velocity only slightly when
      walking on irregular surfaces. Analyses of the temporal gait characteristics,
      i.e. stride time, stance time, double-support time and step frequency, showed no
      statistically significant adjustments. Interestingly, the amputees did not
      increase the stability margins for lateral balance which were calculated based on
      the concept of the "extrapolated center of mass". Furthermore, they did not
      increase their step width, which was already wide when walking on the flat
      surface. However, amputees did increase the lateral component of relative arm
      swing velocity in order to walk stable on irregular surfaces.

PMID- 21176878
TI  - Nucleosome structural studies.
AB  - Chromatin plays a fundamental role in eukaryotic genomic regulation, and the
      increasing awareness of the importance of epigenetic processes in human health
      and disease emphasizes the need for understanding the structure and function of
      the nucleosome. Recent advances in chromatin structural studies, including the
      first structures of nucleosomes containing the Widom 601 sequence and the
      structure of a chromatin protein-nucleosome assembly, have provided new insight
      into stretching of nucleosomal DNA, nucleosome positioning, binding of metal
      ions, drugs and therapeutic candidates to nucleosomes, and nucleosome recognition
      by nuclear proteins. These discoveries ensure promising future prospects for
      unravelling structural attributes of chromatin.

PMID- 21176880
TI  - Retroesophageal aortic arch--a 'Forme Fruste' of interrupted aortic arch.

PMID- 21176881
TI  - Docetaxel maintains its cytotoxic activity under hypoxic conditions in prostate
      cancer cells.
AB  - OBJECTIVE: The efficacy of docetaxel has recently been shown to be increased
      under hypoxic conditions through the down-regulation of hypoxia-inducible-factor
      1alpha (HIF1A). Overexpression of the hypoxia-responsive gene class III beta
      tubulin (TUBB3) has been associated with docetaxel resistance in a number of
      cancer models. We propose that administration of docetaxel to prostate patients
      has the potential to reduce the hypoxic response through HIF1A down-regulation
      and that TUBB3 down-regulation participates in sensitivity to docetaxel. METHODS:
      The cytotoxic effect of docetaxel was determined in both 22Rv1 and DU145 prostate
      cancer cell lines and correlated with HIF1A expression levels under aerobic and
      hypoxic conditions. Hypoxia-induced chemoresistance was investigated in a pair of
      isogenic docetaxel-resistant PC3 cell lines. Basal and hypoxia-induced TUBB3 gene
      expression levels were determined and correlated with methylation status at the
      HIF1A binding site. RESULTS: Prostate cancer cells were sensitive to docetaxel
      under both aerobic and hypoxic conditions. Hypoxic cytotoxicity of docetaxel was
      consistent with a reduction in detected HIF1A levels. Sensitivity correlated with
      reduced basal and hypoxia-induced HIF1A and TUBB3 expression levels. The TUBB3
      HIF1A binding site was hypermethylated in prostate cell lines and tumor
      specimens, which may exclude transcription factor binding and induction of TUBB3
      expression. However, acquired docetaxel resistance was not associated with TUBB3
      overexpression. CONCLUSION: These data suggest that the hypoxic nature of a tumor
      may have relevance as regard to their response to docetaxel. Further
      investigation into the nature of this relationship may allow identification of
      novel targets to improve tumor control in prostate cancer patients.

PMID- 21176883
TI  - Clinical and molecular investigation of 19 Japanese cases of glutaric acidemia
      type 1.
AB  - Glutaric acidemia type 1 (GA1) is a metabolic disease caused by a deficiency of
      glutaryl-CoA dehydrogenase (GCDH). Untreated patients mostly develop severe
      striatal degeneration. More than 200 mutations have been reported in the GCDH
      gene, and common R402W and IVS10-2A>C were found in Caucasian and
      Chinese/Taiwanese, respectively. However, in Japan, genetic mutations have only
      been reported in a few cases. Herein, we report the clinical and molecular basis
      of GA1 in 19 Japanese patients, including six previously reported patients. All
      cases showed high urinary glutaric acid excretion. Eleven patients were severely
      impaired (three patients died), three had mild impairment, and five showed normal
      development. Four of 5 patients that developed normally were detected in the
      presymptomatic stage by neonatal or sibling screening. Nineteen mutations in 26
      alleles were identified, and eight of them (89 or 90delC, Y155C, IVS4+2T>C,
      G244S, Q352X, G354A, K361E, and 1144-1145delGC) were novel. S305L (12.1%, 4/34
      alleles) was found in several cases, suggesting that this mutation is a common
      mutation. In contrast, R402W was not identified and IVS10-2A>C was only found in
      one allele, suggesting that Japanese patients with GA1 show allelic heterogeneity
      and have a different genetic background to patients from other countries. One of
      a pair of sisters with the same mutations (M339V/S305L) lacking residual activity
      was severely retarded, whereas the older girl remains asymptomatic at 22 years of
      age, indicating that genotype does not necessarily predict GA1 phenotype. We
      consistently found that there was no association between genotype and phenotype.
      However, children with mild impairment were diagnosed and treated earlier than
      severely impaired cases {4.7+/-2.5 months (range: 2-8 months) vs. 11.6+/-12.7
      months (range: 4-51 months)}. Our results suggest that early detection and
      treatment but not genotype are associated with better patient outcome,
      reinforcing the importance of neonatal screening.

PMID- 21176884
TI  - Surface muscle pressure as a measure of active and passive behavior of muscles
      during gait.
AB  - While surface electromyography (SEMG) can accurately register electrical activity
      of muscles during gait, there are no methods to estimate muscular force non
      invasively. To better understand the mechanical behavior of muscle, we evaluated
      surface muscle pressure (SMP) in conjunction with SEMG. Changes in anterior thigh
      radial pressure during isometric contractions and gait were registered by
      pressure sensors on the limb. During isometric knee extensions by a single
      subject, SMP waveforms correlated well with SEMG (r=0.97), and SEMG onsets
      preceded those of SMP by 35-40 ms. SMP and SEMG signals were simultaneously
      recorded from the quadriceps of 10 healthy subjects during gait at speeds of 0.4,
      0.8, 1.1, 1.4 and 2.2m/s. Muscle activity onset and cessation times were
      objectively determined for both modalities, and results showed high intra-class
      correlations. SMP waveforms were highly consistent from stride to stride, while
      SEMG waveforms varied widely. SEMG waveforms were typically brief, while SMP
      waveforms tended to be biphasic and outlasted the SEMG by approximately 40% of
      gait cycle at all speeds. These results are consistent with mechanical models of
      muscle, and demonstrate the use of SMP to estimate the timing of knee extensor
      muscle stiffness during gait.

PMID- 21176882
TI  - Research challenges in central nervous system manifestations of inborn errors of
      metabolism.
AB  - The Research Challenges in CNS Manifestations of Inborn Errors of Metabolism
      workshop was designed to address challenges in translating potential therapies
      for these rare disorders, and to highlight novel therapeutic strategies and
      innovative approaches to CNS delivery, assessment of effects and directions for
      the future in the treatment of these diseases. Therapies for the brain in inborn
      errors represent some of the greatest challenges to translational research due to
      the special properties of the brain, and of inborn errors themselves. This review
      covers the proceedings of this workshop as submitted by participants. Scientific,
      ethical and regulatory issues are discussed, along with ways to measure outcomes
      and the conduct of clinical trials. Participants included regulatory and funding
      agencies, clinicians, scientists, industry and advocacy groups.

PMID- 21176885
TI  - A rapid and simple route for the synthesis of lead and palladium nanoparticles in
      tetrazolium based ionic liquid.
AB  - In the present work, we report a novel method for the synthesis of palladium and
      lead nanoparticles by the reduction method in tetrazolium ring based ionic
      liquid. Palladium and lead nanoparticles so-prepared were well characterized by
      powder X-ray diffraction measurements (pXRD), transmission electron microscopy
      (TEM) and quasi elastic light scattering (QELS) techniques. Powder X-ray
      diffraction (pXRD) analysis revealed all relevant Bragg's reflection for crystal
      structure of palladium and lead. Powder X-ray diffraction plots also revealed no
      oxidized material of palladium and lead nanoparticles. TEM showed nearly uniform
      distribution of the particles in methanol and confirmed by QELS. Typical
      applications of palladium nanoparticles include in vitro use and sensor design
      applications. Palladium nanoparticles is also ideal for spin coating, self
      assembly and monolayer formation. Palladium nanoparticles can also be considered
      as potential new catalysts.

PMID- 21176886
TI  - Spectroscopic studies of the interaction between pirimicarb and calf thymus DNA.
AB  - The interaction between pirimicarb and calf thymus DNA in physiological buffer
      (pH 7.4) was investigated with the use of Neutral Red (NR) dye as a spectral
      probe by UV-vis absorption, fluorescence and circular dichroism (CD)
      spectroscopy, as well as viscosity measurements and DNA melting techniques. The
      results revealed that an intercalation binding should be the interaction mode of
      pirimicarb to DNA. CD spectra indicated that pirimicarb induced conformational
      changes of DNA. The binding constants of pirimicarb with DNA were obtained by the
      fluorescence quenching method. The thermodynamic parameters, enthalpy change
      (DeltaHtheta) and entropy change (DeltaStheta) were calculated to be -52.13+/
      2.04 kJ mol(-1) and -108.8+/-6.72 J mol(-1) K(-1) according to the van't Hoff
      equation, which suggested that hydrogen bonds and van der Waals forces might play
      a major role in the binding of pirimicarb to DNA. Further, the alternative least
      squares (ALS) method was applied to resolve a complex two-way array of the
      absorption spectra data, which provided simultaneously the concentration
      information for the three reaction components, pirimicarb, NR and DNA-NR. This
      ALS analysis indicated that the intercalation of pirimicarb into the DNA by
      substituting for NR in the DNA-NR complex.

PMID- 21176887
TI  - P. aeruginosa drives CXCL8 synthesis via redundant toll-like receptors and NADPH
      oxidase in CFTR?F508 airway epithelial cells.
AB  - BACKGROUND: Understanding the mechanisms underlying bacterial-driven inflammation
      and neutrophil recruitment is important to design better therapies for CF. CXCL8
      is an important chemokine found elevated in the airways of CF patients that
      recruits neutrophil to sites of the inflammation. METHODS: Airway epithelial
      cells (AECs) expressing wild-type CFTR or CFTR?F508 were challenged with
      Pseudomonas aeruginosa diffusible material (PsaDM) and the synthesis of CXCL8 was
      measured by quantitative real-time PCR and ELISA in absence or presence of MAPK
      inhibitors, TLR antagonists, glutathione and a NADPH oxidase inhibitor. RESULTS:
      CFTR?F508 AECs secrete more CXCL8 in response to PsaDM than their wild type
      counterpart, which can be reversed by addition of extracellular glutathione or
      incubating AECs at 27 degrees C to favour folding and expression of CFTR at the
      cell membrane. Moreover, in CFTR?F508 AECs, TLR2, TLR4 and TLR5 act redundantly
      to drive CXCL8 synthesis via the activation of NADPH oxidase. DISCUSSIONS: These
      results demonstrate that NADPH oxidase is necessary for CXCL8 synthesis in
      response to TLRs activation by P. aeruginosa.

PMID- 21176888
TI  - Application of single drop liquid-liquid-liquid microextraction for the
      determination of fluoroquinolones in human urine by capillary electrophoresis.
AB  - A simple and novel method of single drop liquid-liquid-liquid microextraction (SD
      LLLME) coupled with capillary electrophoresis (CE) for the determination of six
      fluoroquinolones (FQs) was developed. The method was eventually applied to
      extraction and preconcentration of FQs in human urine samples. Good linear
      relationships were obtained for all analytes in a range of 40-1000 MUg L-1 with
      the correlation coefficients from 0.9913 to 0.9995. The limit of detections
      (LODs) varied from 7.4 to 31.5 MUg L-1 at a signal-to-noise (S/N) of 3. The
      recoveries at two spiking levels were 81.8-104.9% with relative standard
      deviations <8.3%.

PMID- 21176889
TI  - Derivatization of carboxylic acids with 4-APEBA for detection by positive-ion LC
      ESI-MS(/MS) applied for the analysis of prostanoids and NSAID in urine.
AB  - In order to develop a generic positive ionization ESI LC-MS method for a variety
      of interesting substance classes, a new derivatization strategy for carboxylic
      acids was developed. The carboxylic acid group is labeled with the bromine
      containing 4-APEBA reagent based on carbodiimide chemistry. The derivatization
      reaction can be carried out under aqueous conditions, thereby greatly simplifying
      sample preparation. In this paper, the derivatization of carboxylic acids is
      exemplified for the determination of prostanoids and non-steroidal anti
      inflammatory drugs (NSAID). Optimization of the derivatization conditions was
      studied. In order to prove the applicability of the presented approach, we
      applied the described protocol to urine samples from complex regional pain
      syndrome (CRPS) patients and were able to detect several prostanoids not visible
      in the urine of healthy volunteers. Further, the determination of the non
      steroidal anti-inflammatory drug ibuprofen in a urine sample was possible.

PMID- 21176890
TI  - Preimplantation genetic diagnosis: twenty years of practice.
AB  - More than two decades after the first clinical application, preimplantation
      genetic diagnosis (PGD) is an established medical procedure and an accepted
      alternative to conventional prenatal diagnosis for patients at high risk of
      transmitting a genetic disorder to their offspring. The great advantage of PGD is
      that the diagnostic procedure is made already at the embryo stage, before
      transfer to the patient, and the need for pregnancy termination is thereby
      avoided. However, PGD can only be performed in connection with in-vitro
      fertilisation followed by embryo biopsy and genetic analysis of single cells, a
      complex and cumbersome procedure for both the couple as well as the professionals
      involved in the treatment. However, for couples at high risk of having an
      affected child, PGD may be the most attractive alternative to conceive unaffected
      children.

PMID- 21176891
TI  - Human liver peroxisomal alanine:glyoxylate aminotransferase: characterization of
      the two allelic forms and their pathogenic variants.
AB  - The hepatic peroxisomal alanine:glyoxylate aminotransferase (AGT) is a pyridoxal
      5'-phosphate (PLP)-enzyme whose deficiency is responsible for Primary
      Hyperoxaluria Type 1 (PH1), an autosomal recessive disorder. In the last few
      years the knowledge of the characteristics of AGT and the transfer of this
      information into some pathogenic variants have significantly contributed to the
      improvement of the understanding at the molecular level of the PH1 pathogenesis.
      In this review, the spectroscopic features, the coenzyme's binding affinity, the
      steady-state kinetic parameters as well as the sensitivity to thermal and
      chemical stress of the two allelic forms of AGT, the major (AGT-Ma) and the minor
      (AGT-Mi) allele, have been described. Moreover, we summarize the characterization
      obtained by means of biochemical and bioinformatic analyses of the following PH1
      causing variants in the recombinant purified forms: G82E associated with the
      major allele, F152I encoded on the background of the minor allele, and the G41
      mutants which co-segregate either with the major allele (G41R-Ma and G41V-Ma) or
      with the minor allele (G41R-Mi). The data have been correlated with previous
      clinical and cell biology results, which allow us to (i) highlight the functional
      differences between AGT-Ma and AGT-Mi, (ii) identify the structural and
      functional molecular defects of the pathogenic variants, (iii) improve the
      correlation between the genotype and the enzymatic phenotype, (iv) foresee or
      understand the molecular basis of the responsiveness to pyridoxine treatment of
      patients bearing these mutations, and (v) pave the way for new treatment
      strategies. This article is part of a Special Issue entitled: Pyridoxal Phospate
      Enzymology.

PMID- 21176892
TI  - Chemo-bacterial synthesis and immunoreactivity of a brain HNK-1 analogue.
AB  - This work reports the synthesis and the biological validation of a trisaccharide
      analogue of the HNK-1 epitope. The 3-O-sulfo-beta-d-GlcpA-(1->3)-beta-d-Galp-(1
      >4)-beta-d-Glcp-allyl has been prepared by enzymatic glucuronylation of allyl
      lactoside by an engineered recombinant Escherichia coli strain followed by a
      chemoselective sulfation. Subsequent covalent attachment of the ozone-oxidised
      trisaccharide to bovine serum albumin provided a neo-glycoconjugate, which has
      been interrogated with antibodies specific to the human natural killer
      carbohydrate epitope HNK-1. ELISA assays confirmed the absolute requirement of
      the sulfate group for protein recognition and the potential application of this
      synthetic oligosaccharide as HNK-1 surrogate.

PMID- 21176893
TI  - [Pelvic reconstruction after abdominoperineal resection of the rectum].
AB  - Despite the advances in the treatment of cancer of the rectum and the expansion
      of the multimodal therapeutic technique, abdominoperineal resection (APR) still
      needs to be performed as radical treatment in 20-30% of cases. APR of the rectum
      involves a significant morbidity, including intestinal obstruction and wound
      complications, with radiotherapy-induced enteritis being able to develop in 15%
      of cases subjected to post-operative radiotherapy. Furthermore, with the aim of
      improving local oncology results, an extended APR is recommended; a technique
      that requires a perineal reconstruction technique that allows a tension free
      closure in a previously radiated tissue and may prevent perineal hernias
      developing. The objective of this article is to review pelvic and perineal repair
      methods after APR due to cancer, with special attention to the new prosthetic
      repair techniques.

PMID- 21176894
TI  - [Oncosurgical strategies for metastatic liver cancer].
AB  - Patients with liver metastases from colorectal cancer (CRC) present a major
      public health challenge with approximately, 1,2 million cases of CRC occur yearly
      worldwide. Resection of colorectal liver metastases (CRLM) is the only treatment
      offering the possibility of cure and has been shown to provide clear survival
      benefits. However, only 10 to 20% of patients with CRLM are eligible for this
      procedure upfront. During the last decade, major advances in the management of
      CRLM have taken place involving three fields: oncology, interventional radiology,
      and surgery. These advances have increased the resectability rate to 20-30% of
      cases with a 5-year survival of 35-50%. Neoadjuvant treatment with
      chemotherapeutic agents such as irinotecan and oxaliplatin, and hepatic artery
      infusion combined with systemic therapy and biologic agents (bevacizumab,
      cetuximab) play an important role in increasing the number of patients eligible
      to secondary resection. However, with the progressive use of neoadjuvant
      chemotherapy further studies are necessary to answer questions such as the risk:
      benefit ratio in maximizing response rates versus vascular changes in the liver
      (current opinion still divided concerning their importance). These questions
      remain challenging and should not be underestimated. In this review, we have
      described the current oncosurgical strategies employed in patients with
      resectable and non resectable CRLM, their benefits, and future treatment
      strategies.

PMID- 21176895
TI  - [Single incision transumbilical laparoscopic appendectomy: initial experience].
AB  - INTRODUCTION: Appendicitis is the most common abdominal emergency. The treatment
      is surgical and single incision laparoscopic surgery (SILS) involves performing
      laparoscopic surgery through a single transumbilical point, in an attempt to
      improve the results of laparoscopic surgery. MATERIAL AND METHOD: A total of 73
      patients with suspected acute appendicitis were operated on using the SILS
      technique between June 2009 and August 2010. All patients were operated on by the
      same surgical team, and the navel was the only point of entrance. Post-surgical
      pain was assessed using a numerical scale at the time of discharge. RESULTS: None
      of the patients required conversion to conventional laparoscopy. The mean
      surgical time was 40+/-14 (16-80) minutes. There were no complications during or
      after the surgery. The mean post-surgical pain score was 3+/-1 (1-7) and the mean
      hospital stay was 18+/-7 (9-42) hours. CONCLUSION: SILS is a safe and effective
      technique for appendicitis. In the future, the most common surgical procedures
      could be performed through the navel. This would be by surgeons, highly
      experienced in advance laparoscopic surgery in order to introduce this new
      technique safely without increasing morbidity and mortality.

PMID- 21176896
TI  - [Lynch syndrome: genetics and surgery].
AB  - Hereditary nonpolyposis colorectal cancer or Lynch Syndrome, caused by germinal
      mutations in mismatch deoxyribonucleic acid (DNA) repair genes, is the most
      common form of hereditary colorectal cancer. The identification of these
      individuals is not easy and is based on clinical and molecular criteria. A review
      is presented on the genetics and diagnosis in Lynch Syndrome, as well as on its
      surgical management and prevention.

PMID- 21176897
TI  - Staging of rectal cancer by EUS: depth of infiltration in T3 cancers is
      important.
AB  - BACKGROUND: EUS is an established method for staging of rectal cancer.
      Nevertheless, there are few data about the significance of infiltration depth
      measured by EUS. OBJECTIVE: Assessment of accuracy of T and N staging by EUS with
      attention to infiltration depth as provided by EUS. DESIGN: Part retrospective,
      part prospective study. SETTING: Community and tertiary referral hospital,
      covering the period before neoadjuvant therapy for advanced rectal cancer was
      established. PATIENTS: Eighty-three patients (60% men) with untreated rectal
      cancer. INTERVENTION: EUS examination. MAIN OUTCOME MEASUREMENTS: We examined the
      correlation between EUS findings and postoperative histology. T3 cancers as
      diagnosed by EUS were classified into minimally invasive (1-2 mm) or advanced (>2
      mm) tumors depending on the depth of infiltration beyond the muscularis propria.
      RESULTS: Accuracy of T staging and N status was 76% and 63%, respectively.
      Overstaging by EUS was more common in minimally invasive T3 by EUS (uT3) (8 of 16
      [50%]) compared with advanced uT3 tumors (1 of 24 [4%]) (P=.01). Accuracy of EUS
      discrimination between T1/2 and T3/4 in rectal cancer for all but minimally
      invasive uT3 rectal tumors was 88%. LIMITATIONS: Partly retrospective analysis.
      CONCLUSIONS: EUS examination of rectal carcinoma determines T stage with high
      accuracy. Additionally, it provides information beyond T and N staging. The 50%
      probability of overstaging patients with minimally invasive uT3N0 by EUS may
      argue for managing these cancers as stage I disease, ie, to refer the patient for
      surgery without neoadjuvant therapy.

PMID- 21176898
TI  - Performance improvement of PI controllers through dynamic set-point weighting.
AB  - Responses of high-order systems under Ziegler-Nichols tuned PI controllers
      (ZNPIs) are characterized by excessive oscillation with a large overshoot.
      Although, a fixed set-point weighting based PI controller (FSWPI) may decrease
      the overshoot considerably, it fails to reduce the oscillation in the set-point
      response. Moreover, both FSWPI and ZNPI exhibit equally poor load regulation.
      Keeping in mind an overall improved performance, we propose an online dynamic set
      point weighting technique for ZNPIs. The dynamic set-point weighting factor
      (beta(d)) is heuristically derived from the instantaneous process trend.
      Performance of the proposed dynamic set-point weighting based PI controller
      (DSWPI) for various second- and third-order processes including a pH process
      shows a significant improvement during both the set-point and load disturbance
      responses over other methods. Stability and robustness of the proposed DSWPI are
      addressed. Effectiveness of the DSWPI is demonstrated through the real-time
      implementation on a practical DC position control system.

PMID- 21176899
TI  - Management and outcome of interprosthetic femoral fractures.
AB  - INTRODUCTION: Interprosthetic femoral fractures following ipsilateral hip and
      knee arthroplasty are a rare but serious complication in clinical practice. In
      most cases, adequate management of these injuries might constitute a challenging
      problem. However, the literature provides only few data regarding the treatment
      and outcome of interprosthetic femoral fractures, and there are only few
      classifications available, which might assist in finding an appropriate treatment
      concept. The purpose of this study was to analyse our experience in the
      management of interprosthetic femoral fractures following ipsilateral hip and
      knee joint replacement. MATERIALS AND METHODS: We reviewed the clinical and
      radiographic records of 23 patients (15 female and eight male, average age: 79.2
      years) with an interprosthetic fracture after ipsilateral hip and knee joint
      replacement between 1992 and 2008. For the classification of interprosthetic
      femoral fractures, the fractures were divided into three types, depending on the
      fracture site and the adjacency to the prostheses. All patients underwent
      operative stabilisation, either by lateral plate fixation (n=19), by revision
      arthroplasty using a long stem (n=2) or by plate fixation and revision
      arthroplasty (n=2). RESULTS: Referring to the clinical outcome, 16 patients
      returned to their pre-injury activity level and were satisfied with their
      clinical outcome. In six patients, we saw a relevant decrease of hip or knee
      function and severe limitations in gait and activities of daily living. We had a
      mean Harris Hip Score (HHS) of 78.4 points, and a mean Knee injury and
      Osteoarthritis Outcome Score (KOOS) of 71.8 points. Relating to the radiographic
      outcome, successful fracture healing was achieved in 19 of 22 patients (86%)
      within 6 months. Failures of reduction and fixation were noted in four (18%) of
      22 patients. CONCLUSION: We had a satisfactory outcome following individualised
      treatment of interprosthetic femoral fractures following ipsilateral hip and knee
      joint replacement. Compared to the rare data in current literature, we had
      promising functional result and high rate of bony fusion. Regarding the
      complexity and challenges in many of these cases, interprosthetic fractures
      require an adequate analysis of the fracture aetiology and a suitable transfer
      into the best possible treatment concept.

PMID- 21176900
TI  - Surgical results of concomitant treatment of deltoid contracture and rotator cuff
      tear.
AB  - BACKGROUND: Contracture of the deltoid muscle is an uncommon disorder. The
      symptoms usually are nonspecific and the diagnosis may be missed, especially when
      combined with other shoulder disorders, such as rotator cuff lesions. Few reports
      have described the surgical treatment of combined deltoid contracture and a torn
      rotator cuff. The purpose of this study was to share our experiences in the
      diagnosis and treatment of patients, who sustained deltoid contracture combined
      with rotator cuff tearing. MATERIALS AND METHODS: Between April 2001 and December
      2006, 18 consecutive patients underwent concomitant treatment for distal release
      of deltoid contracture and repair of a torn rotator cuff. The mean age at
      operation was 55.1 years. There were eight female and ten male patients. The
      acromial type, winging angle of the scapula and thickest diameter of the deltoid
      fibrotic band were measured using preoperative magnetic resonance imaging
      studies. The abduction-contracture angle, extension-contracture angle, horizontal
      adduction angle and Constant and Murley scores were measured preoperatively and
      at the latest follow-up. RESULTS: There were nine complete rotator cuff tears and
      nine partial tears. At an average of 5 years and 3 months' follow-up, the mean
      abduction-contracture angle significantly improved from 27 degrees  to 0 degrees 
      (p<0.001), the mean extension-contracture angle improved from 13 degrees  to 0
      degrees  (p<0.001), and, the mean horizontal-adduction angle improved from 8
      degrees  to 44 degrees  (p<0.001). The mean Constant score also improved from 69
      points to 95 points (p<0.001). CONCLUSIONS: If a symptomatic torn rotator cuff
      and deltoid contracture co-exist, simultaneous operative treatment of both
      conditions is highly recommended.

PMID- 21176901
TI  - Treatment of ipsilateral concomitant fractures of proximal extra capsular and
      distal femur.
AB  - OBJECTIVES: Ipsilateral concomitant fractures of proximal extracapsular and
      distal femur are rare injuries and pose a great challenge for orthopaedics. In
      this study, we reviewed and examined the approaches and outcomes of this complex
      injury. METHODS: From August 2002 to January 2010, seven patients (six males and
      one female) with a mean age of 39 years (range, 20-48 years) were involved in the
      study. They had suffered from ipsilateral concomitant fractures of proximal
      extracapsular and distal femur, with two cases of unstable intertrochanteric
      fractures, three cases of subtrochanteric fractures and two cases of
      extracapsular femoral neck fractures. The distal femoral fractures were
      categorised based on the Arbeitsgemeinschaft fur Osteosynthes (AO)
      classification: 2, A3; 2, C1; 2, C2 and 1, C3, and the proximal femoral fractures
      were stabilised via nailing, whilst the distal ones via less-invasive
      stabilisation system-distal femur (LISS-DF) plating in all six patients. In the
      one with the 'floating knee' injury, the subtrochanteric fracture was stabilised
      by reversed LISS-DF, and the distal one, by retrograde nailing. The healing of
      each femoral fracture was evaluated radiologically and clinically with follow-up.
      The functional outcomes were assessed through the Friedman and Wyman system.
      RESULTS: The mean follow-up interval was 2 years (range, 1.5-3 years). Six
      femoral fractures healed uneventfully, whilst the one with the 'floating knee'
      injury developed a delayed union postoperatively due to metal failure in 6
      months, and, eventually, a malunion with coxa vara deformity 1.5 years later. The
      clinical functions at the final follow-up were found to be good in five cases,
      and fair and poor in one case each. CONCLUSION: The nailing of a proximal femoral
      fracture and an LISS-DF fixation of a distal one could be a reliable and
      effective approach to handle ipsilateral concomitant fractures of a proximal
      extracapsular and distal femur.

PMID- 21176902
TI  - Treading the tightrope between motherhood and an eating disorder: a qualitative
      study.
AB  - BACKGROUND: Pregnancy is a life event that involves a change in appearance,
      during which the eating behaviour and body of childbearing women is scrutinised
      by others. The impact this has on the thoughts and behaviours of individuals who
      have or have had an eating disorder has been little investigated. OBJECTIVES: A
      qualitative project to provide a deeper understanding of the views of women with
      an eating disorder history about pregnancy and the early stages of motherhood.
      METHODS: Semi-structured interviews were conducted with eight women who were or
      had recently been pregnant. All had an eating disorder history. It explored how
      becoming a mother impacted on thoughts and practices relating to weight, using
      framework analysis. RESULTS: Interviews lasted approximately 80min. The
      overriding concept identified through analysis was the divided loyalties
      participants experienced between putting their child first and disregarding the
      eating disorder. Interpretation of data resulted in the identification by the
      research team of four main themes: fear of failure, transforming body and eating,
      uncertainties about child's shape and emotional regulation. CONCLUSIONS: Three
      types of women were identified among interviewees; those that seemed to be
      'cured' of their eating disorder through motherhood, those that seemed able to
      put their condition on hold during pregnancy and those that seemed unable to
      relinquish dangerous behaviours. Issues relating to control, identity and
      perfectionism may impede some women's ability to enjoy pregnancy and motherhood
      if they have an eating disorder history.

PMID- 21176903
TI  - Adherence to a guideline on cardiovascular prevention: a comparison between
      general practitioners and practice nurses.
AB  - BACKGROUND: Patient non-compliance with prescribed treatment is an important
      factor in the lack of success in cardiovascular prevention. Another important
      cause is non-adherence of caregivers to the guidelines. It is not known how
      doctors and nurses differ in the application of guidelines. Patient compliance to
      treatment may vary according to the type of caregiver. OBJECTIVE: To compare
      adherence to cardiovascular prevention delivered by practice nurses and by
      general practitioners. SETTING: Six primary health care centres in the
      Netherlands (25 general practitioners, six practice nurses). METHODS: 701 high
      risk patients were included in a randomised trial. Half of the patients received
      nurse-delivered care and half received care by general practitioners. For 91% of
      the patients treatment concerned secondary prevention. The Dutch guideline on
      cardiovascular prevention was used as protocol. A structured self-administered
      questionnaire was sent by post to patients. Data were extracted from the practice
      database and the questionnaire. RESULTS: Intervention was received by 77% of
      respondents who visited the practice nurse compared to 57% from the general
      practitioner group (OR = 2.56, p < 0.01). More lifestyle intervention was given
      by the practice nurse; 46% of patients received at least one lifestyle
      intervention (weight, diet, exercise, and smoking) compared to 13% in general
      practitioner group (OR = 3.24, p < 0.001). In addition, after one year more
      patients from the practice nurse group used cardiovascular drugs (OR = 1.9, p =
      0.03). Nurses inquired more frequently about patient compliance to medical
      treatment (OR = 2.1, p < 0.01). Regarding patient compliance, no statistical
      difference between study groups in this trial was found. CONCLUSION: Practice
      nurses adhered better to the Dutch guideline on cardiovascular prevention than
      general practitioners did. Lifestyle intervention advice was more frequently
      given by practice nurses. Improvement of cardiovascular prevention is still
      necessary. Both caregivers should inquire about patient adherence on a regular
      basis.

PMID- 21176904
TI  - Psychometric properties of the Chinese version of the Life Attitude Schedule (LAS
      C) in a sample of Taiwanese adolescents.
AB  - BACKGROUND: Although prior research has proposed that several risk factors are
      conceptually and positively related to suicidal behavior, researchers have also
      suggested that suicide may be multifaceted. The Life Attitude Schedule (LAS)
      measures a broad range of suicide-related behaviors, including life-enhancing and
      life-threatening behaviors. OBJECTIVE: This study aimed to translate the LAS into
      Chinese and evaluate the psychometric properties of the new version (LAS-C).
      DESIGN: A cross-sectional and descriptive design was used. SETTING: Data were
      collected from high schools in the city of Taipei in northern Taiwan.
      PARTICIPANTS: A convenience sample of 1492 high school students was recruited
      from five high schools in Taipei. METHODS: We used the Multi-Health Systems (MHS)
      translation policy to guide the translation process. Reliability was evaluated by
      internal consistency (represented by Cronbach's alpha coefficients) and test
      retest (represented by intraclass correlation). Validity was demonstrated by
      content, convergent, divergent, concurrent, and contrast group comparison.
      Confirmatory factor analysis was further used to examine the theoretical model
      and to support construct validity. RESULTS: The Cronbach's alpha coefficient for
      the whole scale of the LAS-C and its subscales ranged from 0.70 to 0.91. The
      Intraclass Correlation Coefficient (ICC) ranged from 0.76 to 0.89 on the whole
      scale and its subscales, and were all statistically significant, at least at the
      p<0.05 level, indicating good stability over a three-week period. Validity was
      supported by a Content Validity Index (CVI) of 0.99, convergent, divergent,
      current, and contrast group comparison validity. Confirmatory factor analysis
      supported the theoretical model, further providing solid evidence of construct
      validity. CONCLUSIONS: The LAS-C has proper psychometric properties. Future
      studies must be conducted to shorten the items to form a briefer version.

PMID- 21176906
TI  - Does medio-lateral motion occur in the normal knee? An in-vitro study in passive
      motion.
AB  - Medio-lateral translation during knee flexion continues to raise controversy.
      Small population sizes, small joint flexion ranges, less-reliable measurement
      techniques and disparate experimental conditions led to inconsistent reports in
      the past. To study this subject with more accurate and reliable measurements, we
      carried out femur and tibia tracking in 22 intact cadaver knees during passive
      joint motion using a state-of-the-art surgical navigation system. Trackers with
      active light-emitting diodes were fixed onto the femur and tibia, and an
      instrumented pointer was used to digitize a number of anatomical landmarks.
      International recommendations were adopted for anatomical-based reference frame
      definitions and joint kinematic analysis. For the first time, knee joint
      translations were reported in both the femoral and tibial reference frames, and
      over a flexion/extension arc as large as 140 degrees . During flexion, in the
      femoral reference frame, the center of the tibial plateau moved 4.8 +/- 2.8mm
      medially when averaged over the specimens. In the tibial frame, the knee center
      moved 13.3 +/- 5.7 mm laterally. The relative femoral-to-tibial medio-lateral
      translation was, on average over the specimens, nearly 20% of the width of the
      tibial plateau, and can be as large as 35%. Medio-lateral translation occurs in
      the natural normal knee joint.

PMID- 21176905
TI  - Association of low leptin with cardiovascular events and mortality in patients
      with stable coronary artery disease: the Heart and Soul Study.
AB  - OBJECTIVE: Leptin is an adipokine with both protective and harmful effects on the
      cardiovascular (CV) system. Prior studies evaluating the association between
      leptin and CV outcomes have yielded conflicting results. Thus, we sought to
      investigate the relationship between leptin and CV events and mortality in
      patients with chronic stable coronary artery disease (CAD). METHODS: We performed
      a prospective cohort study of 981 outpatients with stable CAD. Leptin levels were
      measured in fasting venous samples at baseline. We used proportional hazards
      models to evaluate the association of baseline leptin with subsequent CV events
      (myocardial infarction, stroke, transient ischemic attack) and death. RESULTS:
      During a mean follow-up of 6.2+/-2.1 years, there were 304 deaths, 112 myocardial
      infarctions, and 52 strokes/TIAs. In models adjusted for age, sex, and race, low
      leptin was associated with a 30% increased risk of the combined outcome (HR 1.30,
      CI 1.05-1.59, p=0.01). After further adjustment for obesity, traditional CV risk
      factors and biomarkers, low leptin remained associated with a 37% increased risk
      of events (HR 1.37, CI 1.06-1.76, p=0.02). CONCLUSIONS: Low leptin is associated
      with increased CV events and mortality in patients with stable coronary artery
      disease. This association is independent of known factors affecting leptin
      levels, including gender and obesity.

PMID- 21176907
TI  - The role of the dual nature of ionic liquids in the reversed-phase liquid
      chromatographic separation of basic drugs.
AB  - The cationic nature of basic drugs gives rise to broad asymmetrical
      chromatographic peaks with conventional C18 columns and hydro-organic mixtures,
      due to the ionic interaction of the positively charged solutes with the free
      silanol groups on the alkyl-bonded reversed-phase packing. Ionic liquids (ILs)
      have recently attracted some attention to reduce this undesirable silanol
      activity. ILs are dual modifiers (with a cationic and anionic character), which
      means that both cation and anion can be adsorbed on the stationary phase, giving
      rise to interesting interactions with the anionic free silanols and the cationic
      basic drugs. A comparative study of the performance of four imidazolium-based ILs
      as modifiers of the chromatographic behaviour of a group of beta-blockers is
      shown. The ILs differed in the adsorption capability of the cation and anion on
      C18 columns. Mobile phases without additive and containing a cationic
      (triethylamine, TEA) or anionic (sodium dodecyl sulphate, SDS) additive were used
      as references for the interpretation of the behaviours. The changes in the nature
      of the chromatographic system, at increasing concentration of the additives, were
      followed based on the changes in retention and peak shape of the beta-blockers.
      The silanol suppressing potency of the additives, and the association constants
      between the solutes and modified stationary phase or additive in the mobile
      phase, were estimated. The study revealed that SDS and the ionic liquid 1-hexyl-3
      methylimidazolium tetrafluoroborate are the best enhancers of chromatographic
      peak shape among those studied.

PMID- 21176908
TI  - Performance of hexamer peptide ligands for affinity purification of
      immunoglobulin G from commercial cell culture media.
AB  - Previous work has reported on the identification and characterization of the
      hexapeptide ligands HWRGWV, HYFKFD, and HFRRHL for the affinity capture of IgG
      through specific binding to its Fc fragment. This paper addresses issues related
      to the successful application of these ligands, on a commercial methacrylate
      chromatographic resin, for the purification of IgG from mammalian cell culture
      fluids. The concentrations of sodium chloride and sodium caprylate in the binding
      buffer were optimized to maximize the purity and yield of IgG upon elution.
      Screening of several regeneration conditions found that either 2M guanidine-HCl
      or a combination of 0.85% phosphoric acid followed by 2M urea resulted in
      complete recovery of the IgG adsorption capacity and that the column could be
      reused over many cycles. The hexapeptide ligands were used for the purification
      of humanized and chimeric monoclonal antibodies from two commercial CHO cell
      culture fluids. The chimeric MAb of IgG1 subclass was purified using the HWRGWV
      resin whereas the humanized MAb of IgG4 subclass was purified using the HWRGWV,
      HYFKFD and HFRRHL resins. The purities and yields obtained for both the MAbs were
      found to be higher than 94% and 85% respectively. These results compare well with
      the yields and purities obtained using Protein G columns. The residual DNA and
      host cell protein reduction obtained by the HWRGWV resin was in the range of 4
      log reduction value (LRV) and 2 LRV respectively, comparable to those reported
      for Protein A resins. The dynamic binding capacity of all three peptide resins
      for the humanized monoclonal antibody was in the range of 20mg/mL.

PMID- 21176909
TI  - Inertial separation in a contraction-expansion array microchannel.
AB  - We report a contraction-expansion array (CEA) microchannel that allows inertial
      size separation by a force balance between inertial lift and Dean drag forces in
      fluid regimes in which inertial fluid effects become significant. An abrupt
      change of the cross-sectional area of the channel curves fluid streams and
      produces a similar effect compared to Dean flows in a curved microchannel of
      constant cross-section, thereby inducing Dean drag forces acting on particles. In
      addition, the particles are influenced by inertial lift forces throughout the
      contraction regions. These two forces act in opposite directions each other
      throughout the CEA microchannel, and their force balancing determines whether the
      particles cross the channel, following Dean flows. Here we describe the physics
      and design of the CEA microfluidic device, and demonstrate complete separation of
      microparticles (polystyrene beads of 4 and 10 MUm in diameter) and efficient
      exchange of the carrier medium while retaining 10 MUm beads.

PMID- 21176910
TI  - Insights into chiral recognition mechanisms in supercritical fluid
      chromatography. I. Non-enantiospecific interactions contributing to the retention
      on tris-(3,5-dimethylphenylcarbamate) amylose and cellulose stationary phases.
AB  - In this series of papers, we use a systematic approach to investigate the factors
      responsible for enantio-recognition in supercritical fluid chromatography (SFC)
      on chiral stationary phases (CSPs). In this first part, the interactions
      contributing to the retentions of the achiral solutes are measured with a
      modified version of the solvation parameter model. Since stereospecific
      interactions were not accounted for in the classical linear solvation energy
      relationship using Abraham descriptors, we introduce two additional descriptors,
      flexibility and globularity, to rationally quantify the stereochemical properties
      that may significantly affect enantiomeric resolutions. Two polysaccharide
      stationary phases presenting identical bonded groups on different polysaccharide
      backbones, namely tris-(3,5-dimethylphenylcarbamate) on amylose and on cellulose,
      are compared using 230 achiral and structurally diverse solutes. The experimental
      results are evaluated based on statistics and the chemical intuition of the
      chromatographic systems.

PMID- 21176911
TI  - Separation characteristics of fatty acid methyl esters using SLB-IL111, a new
      ionic liquid coated capillary gas chromatographic column.
AB  - The ionic liquid SLB-IL111 column, available from Supelco Inc., is a novel fused
      capillary gas chromatography (GC) column capable of providing enhanced
      separations of fatty acid methyl esters (FAMEs) compared to the highly polar
      cyanopropyl siloxane columns currently recommended for the separation of cis- and
      trans isomers of fatty acids (FAs), and marketed as SP-2560 and CP-Sil 88. The
      SLB-IL111 column was operated isothermal at 168 degrees C, with hydrogen as
      carrier gas at 1.0 mL/min, and the elution profile was characterized using
      authentic GC standards and synthetic mono-unsaturated fatty acids (MUFAs) and
      conjugated linoleic acid (CLA) isomers as test mixtures. The SLB-IL111 column
      provided an improved separation of cis- and trans-18:1 and cis/trans CLA isomers.
      This is the first direct GC separation of c9,t11- from t7,c9-CLA, and t15-18:1
      from c9-18:1, both of which previously required complimentary techniques for
      their analysis using cyanopropyl siloxane columns. The SLB-IL111 column also
      provided partial resolution of t13/t14-18:1, c8- from c6/c7-18:1, and for several
      t,t-CLA isomer pairs. This column also provided elution profiles of the geometric
      and positional isomers of the 16:1, 20:1 and 18:3 FAMEs that were complementary
      to those obtained using the cyanopropyl siloxane columns. However, on the SLB
      IL111 column the saturated FAs eluted between the cis- and trans MUFAs unlike
      cyanopropyl siloxane columns that gave a clear separation of most saturated FAs.
      These differences in elution pattern can be exploited to obtain a more complete
      analysis of complex lipid mixtures present in ruminant fats.

PMID- 21176912
TI  - Copolymers sensitive to temperature and pH in water and in water+oil mixtures: A
      DSC, ITC and volumetric study.
AB  - Block copolymer micelles are receiving an increasing interest because of the
      variety of structures and the possibilities to tune them by changing external and
      internal parameters achieving the desired properties for a specific purpose. We
      have investigated the acid/base behavior, self-assembling and solubilization
      ability towards polar oils of star-like copolymers named Tetronics. They are
      composed of branched four-arms each one consisting of two blocks made of EO and
      PO units linked to the diethylenediamine group, which confers pH response
      ability. The copolymers T1107 and T90R4 were studied with a sequential and
      reverse architecture. The thermodynamics of the acid/base equilibrium was studied
      by ITC. The aggregation of T1107 in water was analyzed as functions of pH,
      composition and temperature. The enhanced oil solubilization in the aqueous T1107
      aggregates was widely investigated highlighting the role of the oil structure,
      composition, temperature and pH. As a general result, the oil induces the
      copolymer aggregation and the solubilization power of micelles is tunable by
      changing the pH. Efforts have been devoted to model the calorimetric data in
      order to achieve the thermodynamic properties of the involved process. Finally,
      we showed that the Tetronic micelles are more promising than the conventional
      surfactants micelles because of the larger solubilization power and flexibility
      of the macromolecular system.

PMID- 21176913
TI  - Selective and self-guided micro-ablation of tissue with plasmonic nanobubbles.
AB  - BACKGROUND: The accuracy, selectivity, and safety of surgical and laser methods
      for tissue elimination are often limited at microscale. MATERIALS AND METHODS: We
      developed a novel agent, the plasmonic nanobubble (PNB), for optically guided
      selective elimination of the target tissue with micrometer precision. PNBs were
      tested in vitro in the two different models of superficial tumors and vascular
      plaques. RESULTS: PNBs were selectively generated around gold nanoparticles
      (delivered to the target tissues) with short laser pulses. Monolayers of
      cancerous cells and atherosclerotic plaque tissue were eliminated with PNBs with
      micrometer accuracy and without thermal and mechanical damage to collateral
      normal tissues. The effect of the PNB was dynamically controlled through the
      fluence of laser pulses (532 nm, duration 0.5 and 10 ns) and was guided through
      the optical scattering by PNB. CONCLUSIONS: Plasmonic nanobubbles were shown to
      provide precise, tunable, selective, and guided ablation of tissue at a
      microscopic level and could be employed as a new generation of surgical tools.

PMID- 21176914
TI  - The role of Surgical Champions in the American College of Surgeons National
      Surgical Quality Improvement Program--a national survey.
AB  - BACKGROUND: The American College of Surgeons National Surgical Quality
      Improvement Program (ACS NSQIP) empowers surgeons and medical centers to reliably
      collect, analyze, and act on clinically collected outcomes data. How individual
      ACS NSQIP leaders designated as Surgeon Champions (SC) utilize the ACS NSQIP at
      the hospital level and the obstacles they encounter are not well studied.
      MATERIALS AND METHODS: All SC representing the 236 hospitals participating in the
      ACS NSIQP were invited to complete a survey designed to assess the role of the
      SC, data use, continuous quality improvement (CQI) efforts, CQI culture, and
      financial implications. RESULTS: We received responses from 109 (46.2%) SC. The
      majority (72.5%) of SC were not compensated for their CQI efforts. Factors
      associated with demonstrable CQI efforts included longer duration of
      participation in the program, frequent meetings with clinical reviewers, frequent
      presentation of data to administration, compensation for Surgical Champion
      efforts and providing individual surgeons with feedback (all P < 0.05). Almost
      all SC stated ACS NSQIP data improved the quality of care that patients received
      at the hospital level (92.4%) and that the ACS NSQIP provided data that could not
      be obtained by other sources (95.2%). All SCs considered future funding for
      participation in the ACS NSQIP secure. CONCLUSIONS: Active use of ACS NSQIP data
      provide SC with demonstrable CQI by regularly reviewing data, having frequent
      interaction with clinical reviewers, and frequently sharing data with hospital
      administration and colleagues. SC thus play a key role in successful quality
      improvement at the hospital level.

PMID- 21176915
TI  - Venous thromboembolic disease in trauma and surveillance ultrasonography.
AB  - BACKGROUND: The literature reports a wide variation in the incidence of venous
      thromboembolic (VTE) disease in trauma patients. The performance of routine
      surveillance venous duplex ultrasound of bilateral lower extremities is
      controversial. Furthermore, recent examinations of the national trauma databank
      registry have suggested that routine duplex surveillance is associated with
      higher deep venous thrombosis (DVT) detection rates. MATERIALS AND METHODS: We
      examined the incidence and risk factors for VTE disease in 2827 trauma patients
      admitted over a 2-y period to a state-verified level I trauma center. Detailed
      chart review was carried out for patients with VTE disease. We then evaluated the
      effects of a routine bilateral lower extremity duplex surveillance guideline on
      VTE detection in the subset of injury patients admitted to the trauma service.
      RESULTS: We found an approximately 2% incidence of venous thromboembolic disease
      in a mostly blunt trauma population. Amongst patients with VTE disease, the most
      common risk factors were obesity and significant head injury. We then evaluated
      the 998 patients with injury who were admitted to the trauma service 1 y before
      and after surveillance guideline implementation. Despite a nearly 5-fold increase
      in the number of duplex scans, with a substantial increase in cost, we found no
      significant difference in the incidence of DVT. CONCLUSIONS: Our preliminary data
      argue against the use of routine duplex surveillance of lower extremities for DVT
      in trauma patients. A larger, prospective analysis is necessary to confirm these
      findings.

PMID- 21176916
TI  - Bicycle helmet legislation and injury patterns in trauma patients under age 18.
AB  - BACKGROUND: The California statewide helmet law was enacted in 1994, and required
      all cyclists under age 18 y to be helmeted when riding a bicycle. The purpose of
      this study is to describe helmet use patterns, rates of head and intra-abdominal
      injury in Los Angeles County before and after helmet legislation, and to
      determine if increasing helmet use is changing injury patterns. METHODS: We
      conducted a retrospective review of trauma patients under age 18 y in the Los
      Angeles County trauma database between 1992 and 2009 injured while riding
      bicycles. We examined the variables of age, gender, race, Glasgow Coma Score,
      Injury Severity Score, presence of head injury, presence of abdominal injury, and
      use of protective helmet. RESULTS: During this time period, there were 44,187
      injured children less than 18 y of age, and there were 1684 bike-related traumas
      with data on helmet use. Injury patterns did not change after the helmet law,
      with head injuries predominating. CONCLUSIONS: The rate of helmet use did not
      change after California legislation, and head injury remains a major source of
      morbidity. Rates of abdominal injury over this time period did not change. Novel
      strategies are needed to increase helmet use in at-risk populations.

PMID- 21176917
TI  - Prognostic factors for renal dysfunction after nephrectomy in renal cell
      carcinomas.
AB  - OBJECTIVE: To explore the prognostic factors for renal dysfunction after
      nephrectomy in patients with renal cell carcinomas. METHODS: Two hundred twenty
      five patients from 2003 to 2010 were analyzed, who have undergone partial
      nephrectomy or radical nephrectomy for renal tumor, of size <=4 cm, with normal
      contralateral kidney. The glomerular filtration rate was computed with the four
      variable modification of diet in renal dysfunction (MDRD) criterion. Renal
      dysfunction was defined as GFR of < 60 mL/min per 1.73 m(2). We applied Cox
      proportional hazards model to analyze demographic and clinicopathologic
      parameters to determine the variables independently associated with the
      development of renal dysfunction. RESULTS: One hundred twenty-nine out of 225
      patients were included in the partial nephrectomy group, while 96 patients were
      in the radical nephrectomy groups; 97 out of 225 patients developed renal
      dysfunction: 86 out of 97 in the radical nephrectomy group and 11 out of 97 in
      the partial nephrectomy group. The 2-y probability of absence of renal
      dysfunction with partial nephrectomy or radical nephrectomy was 95.7% and 58.3%,
      respectively (P < 0.001). Among 20 patients with diabetes, 12 (60.0%) developed
      renal dysfunction: 10 patients underwent an RN and two underwent a PN. The 2-y
      probability of absence of renal dysfunction with and without diabetes was 46.5%
      and 76.4%, respectively (P = 0.006). Multivariate analysis showed that age (P =
      0.001), type of operation (P < 0.001), preoperative GFR (P = 0.001), and diabetes
      (P = 0.042) were associated with the development of renal dysfunction.
      CONCLUSIONS: The results of this study show that nephron-sparing surgery (NSS)
      for renal cell carcinomas should be attempted to prevent renal dysfunction in all
      eligible patients.

PMID- 21176918
TI  - Tetrandrine induces apoptosis and triggers caspase cascade in human bladder
      cancer cells.
AB  - BACKGROUND: Tetrandrine is known to exert anti-tumor effects, however, little is
      known about its effect on human bladder carcinoma. In this study, employing two
      different human bladder cancer cell lines, 5637 and T24, which represent high
      risk superficial bladder cancer (5637) and high-grade bladder cancer (T24), we
      tested tetrandrine-induced apoptosis and growth inhibition in bladder carcinoma
      cell lines and investigated the possible mechanisms. MATERIALS AND METHODS:
      Growth inhibition and apoptosis induction was determined by MTT assay and flow
      cytometry analysis, respectively. Activation of caspases were analyzed by Western
      blotting and caspase colorimetric assay. The collapse of mitochondrial membrane
      potential (DeltaPsi(m)) and subcellular distribution of cytochrome c was
      determined by JC-1 staining and Western blotting, respectively. RESULTS:
      Tetrandrine treatment showed strong growth inhibitory and apoptotic effects on
      human bladder cancer 5637 and T24 cells in a concentration-dependent manner.
      Additionally, induction of apoptosis by tetrandrine was associated with a very
      strong and prominent caspase-9, caspase-8, and caspase-3 activation as well as
      PARP cleavage. Flow cytometric studies revealed that tetrandrine induced a dose
      dependent loss of DeltaPsi(m), which was accompanied by the release of cytochrome
      c from mitochondria to the cytosol. CONCLUSION: Taken together, this study
      provided the first evidence that tetrandrine imparted inhibitory and apoptotic
      activity in human bladder cancer cells. The tetrandrine-induced apoptosis might
      be related to the activation of the caspase cascade and mitochondrial pathway.
      Our results suggest that tetrandrine merits further in vivo investigation as a
      novel bladder cancer chemopreventive and chemotherapeutic agent in the clinical
      setting.

PMID- 21176919
TI  - Imageless navigation system does not improve component rotational alignment in
      total knee arthroplasty.
AB  - BACKGROUND: The aim of computer-assisted surgery is to improve accuracy and limit
      the range of surgical variability. However, a worldwide debate exists regarding
      the importance and usefulness of computer-assisted navigation for total knee
      arthroplasty (TKA). The main purpose of this study is to summarize and compare
      the radiographic outcomes of TKA performed using imageless computer-assisted
      navigation compared with conventional techniques. MATERIALS AND METHODS: An
      electronic search of PubMed, EMBASE, Web of Science, and Cochrane library
      databases was made, in addition to manual search of major orthopedic journals. A
      meta-analysis of 29 quasi-randomized/randomized controlled trials (quasi
      RCTs/RCTs) and 11 prospective comparative studies was conducted through a random
      effects model. Additional a priori sources of clinical heterogeneity were
      evaluated by subgroup analysis with regard to radiographic methods. RESULTS: When
      the outlier cut-off value of lower limb axis was defined as +/-2 degrees  or +/-3
      degrees  from the neutral, the postoperative full-length radiographs demonstrated
      that the risk ratio was 0.54 or 0.39, respectively, which were in favor of the
      navigated group. When the cut-off value used for the alignment in the coronal and
      sagittal plane was 2 degrees  or 3 degrees , imageless navigation significantly
      reduced the outlier rate of the femoral and tibial components compared with the
      conventional group. Notably, computed tomography scans demonstrated no
      statistically significant differences between the two groups regarding the
      outliers in the rotational alignment of the femoral and tibial components;
      however, there was strong statistical heterogeneity. CONCLUSIONS: Our results
      indicated that imageless computer-assisted navigation systems improve lower limb
      axis and component orientation in the coronal and sagittal planes, but not the
      rotational alignment in TKA. Further multiple-center clinical trials with long
      term follow-up are needed to determine differences in the clinical and functional
      outcomes of knee arthroplasties performed using computer-assisted techniques.

PMID- 21176920
TI  - Consequences of pneumoperitoneum on liver ischemia during laparoscopic portal
      triad clamping in a swine model.
AB  - BACKGROUND: Portal triad clamping (PTC) may be required during laparoscopic liver
      resection to limit blood loss. The aim of this study was to test in a swine model
      the hypothesis that during laparoscopic PTC, increased intraperitoneal pressure
      may alter hepatic vein reverse circulation, inducing a more severe hepatic
      ischemia compared with PTC performed in laparotomy. METHODS: Fifteen pigs were
      randomized into three groups: laparoscopy (1 h of pneumoperitoneum at 15 mmHg and
      3 h of surveillance), open PTC (1 h PTC through laparotomy and 3 h of
      reperfusion), and laparoscopic PTC (1 h PTC with 15 mmHg pneumoperitoneum and 3 h
      of reperfusion). PTC was performed under mesenteric decompression using a veno
      venous splenofemoral bypass. Hepatic partial oxygen tension and microcirculatory
      flow were continuously measured using a Clarke-type electrode and a laser Doppler
      flow probe, respectively. Liver consequences of PTC was assessed by right atrium
      serum determination of transaminases, creatinine, bilirubin, INR, and several
      ischemia/reperfusion parameters, drawn before PTC (T0), before unclamping (T60),
      and 1 (T120) and 3 h after reperfusion (T240). Histology was performed on T240
      liver biopsies. RESULTS: Compared with open PTC, laparoscopic PTC produced a more
      rapid and more severe decrease in hepatic oxygen tension, indicating a more
      severe tissular hypoxia, and a more severe decrease in hepatic microcirculatory
      flow, indicating a decrease in hepatic backflow. At T240, the laparoscopic PTC
      livers suffered from a higher degree of hepatocellular damage, shown by higher
      transaminases and increased necrotic index at pathology. CONCLUSIONS: These
      results indicate that in this pig model, laparoscopic PTC induces a more severe
      liver ischemia, related to decreased hepatic oxygen content and decreased hepatic
      backflow. If confirmed by clinical studies, these results may indicate that
      caution is necessary when performing prolonged PTC during laparoscopic hepatic
      resection, particularly in cirrhotic or steatotic livers.

PMID- 21176921
TI  - Irinotecan injures tight junction and causes bacterial translocation in rat.
AB  - BACKGROUND: Tight junctions are an essential component of intestinal epithelial
      barriers. Claudin-1, occludin, and ZO-1 are the components of tight junction. The
      purpose of this study was to investigate whether irinotecan induces bacterial
      translocation in rats, and thus elucidate the relationship between tight junction
      and bacterial translocation. METHODS: Ten rats were divided into two groups: Five
      were treated with irinotecan and five were not treated with irinotecan, the
      control group. Irinotecan treated rats were administrated irinotecan 250 mg/kg
      intraperitoneally on days designated 0 and 1, were then killed at 48 h after
      treatment, and tissues were collected for analysis. Controls were treated with a
      saline solution. RESULTS: In eighty percent of irinotecan treated rats, bacteria
      were detected in the mesenteric lymph node or spleen. Large intestinal resistance
      of the rats was decreased. On the contrary, small intestinal resistance
      increased. Claudin-1 protein expression of both the small and large intestine
      decreased (P < 0.05), occludin protein expression of the small intestine
      decreased (P < 0.05), and occludin protein expression of the large intestine had
      decreasing tendency (P = 0.07) in irinotecan treated rats. In irinotecan treated
      rats, claudin-1 mRNA of the small intestine decreased (P < 0.05), claudin-1 mRNA
      of large intestine had a tendency to decrease (P = 0.05), occludin mRNA of both
      small and large intestine decreased (P < 0.05). CONCLUSIONS: Irinotecan injures
      claudin-1 and occludin. It causes disorders in the intestinal epithelial barrier
      and induces bacterial translocation.

PMID- 21176923
TI  - Functional parkin promoter polymorphism in Parkinson's disease: new data and meta
      analysis.
AB  - BACKGROUND: A functional SNP (rs9347683) in the promoter region of the parkin
      gene had been implicated as a risk factor in older Parkinson's disease (PD)
      patients. METHODS: Using a case-control methodology, we genotyped the SNP in the
      promoter region of the parkin gene to investigate their association with risk of
      PD and conducted a pooled analysis of published papers in the English literature.
      RESULTS: A total of 1087 study subjects comprising 595 patients with PD and 492
      unrelated healthy controls were recruited. The frequency of "GG" genotype in the
      elderly sub-group (>= 65 years) was higher in PD compared to controls (OR=1.11)
      though we did not observe any difference in allele or genotype frequencies
      between the cases and the controls (P>0.05) in the overall PD population. Those
      with genotype "GG" were associated with a higher Hoehn-Yahr stage compared with
      PD patients carrying "GT"+"TT" (P=0.040). A pooled analysis involving more than
      >3000 subjects revealed that the frequency of genotypes in PD patients did not
      differ from the controls (OR=0.98, 95% CI: 0.86-1.12). However, in the group >=
      65 years of age, the "GG" genotype was higher in PD (OR=1.51, 95% CI: 1.06-2.13,
      P=0.020) among the ethnic Chinese. CONCLUSIONS: While we did not demonstrate a
      significant association of the parkin promoter polymorphism with PD in our
      sample, the pooled data suggest that the variant may increase the risk of PD in
      the more elderly population among the ethnic Chinese, suggesting possible
      ethnicity-specific effect. Further in vitro and in vivo studies to evaluate this
      functional parkin variant are warranted.

PMID- 21176922
TI  - Tumor location predicts survival in cutaneous head and neck melanoma.
AB  - BACKGROUND: Prior studies documented poorer outcomes in patients with cutaneous
      head and neck melanoma (CHNM) relative to those with melanoma at other sites. We
      evaluated survival differences attributable to tumor location in patients with
      CHNM. METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER)
      database for patients undergoing surgery for CHNM from 1988 to 2006, excluding
      patients without biopsy-proven diagnoses, those diagnosed at autopsy, and
      patients with distant metastases. Using the Kaplan-Meier method, we assessed
      patient, tumor, and treatment-specific factors on overall survival (OS) and
      melanoma specific survival (MSS). Cox proportional hazards models assessed the
      role of tumor location (ear, eyelid, face, lip, scalp/neck) on OS and MSS, while
      controlling for patient age, gender, race, tumor thickness, tumor ulceration,
      lymph node status, histologic subtype, type of surgery, and use of radiation.
      Risks of overall and melanoma-specific mortality were reported as hazard ratios
      (HR) with 95% confidence intervals (CI). RESULTS: Among 27,097 patients, 10-y
      rates of OS and MSS were 56.1% and 84.7%, respectively. On multivariate analysis,
      scalp/neck primary site was associated with an increased risk of overall (HR
      1.20, CI 1.14-1.26; P < 0.001) and melanoma-specific mortality (HR 1.64, CI 1.49
      1.80, P < 0.001) relative to melanomas of the face. Tumors of the lip had poorer
      MSS (HR 1.55; CI 1.05-2.28, P = 0.03) but not OS (HR 1.03, CI 0.80-1.34; P =
      0.80). CONCLUSIONS: Patients with melanomas of the scalp/neck have poorer OS and
      MSS and those with lip melanomas have poorer MSS. These anatomic areas should not
      be overlooked when performing skin examinations.

PMID- 21176924
TI  - Cervical pachymeningeal hypertrophy as the initial and cardinal manifestation of
      mucopolysaccharidosis type I in monozygotic twins with a novel mutation in the
      alpha-L-iduronidase gene.
AB  - We describe a pair of monozygotic twins with an attenuated form of
      mucopolysaccharidosis type I (MPS-I). At age 24, they both developed cervical
      myelopathy as a cardinal manifestation. They each also had mild valve
      abnormalities and both inguinal and umbilical hernia, however, other
      characteristic features of MPS-I were absent or very mild. Magnetic resonance
      imaging revealed the cervical cord compressed by pachymeningeal hypertrophy.
      Surgery with dural plasty and laminoplasty resulted in decompression of the
      cervical cord with clinical improvement, revealing marked thickening of the dura
      mater. Both patients showed a marked decrease of alpha-L-iduronidase (IDUA)
      activity with c.252insC (p.P55fsX62; known) and c.1209C>A (p.T374N; novel)
      mutations of the IDUA gene (IDUA). Patients with MPS-I have been reported to
      present with various clinical phenotypes and severities even if they have
      identical mutations of IDUA. The quite similar, unique phenotype in monozygotic
      twins suggests that not only IDUA mutation but also other genetic factors than
      IDUA markedly influence the clinical manifestations of MPS-I.

PMID- 21176925
TI  - Detoxification of cruciferous phytoalexins in Botrytis cinerea: spontaneous
      dimerization of a camalexin metabolite.
AB  - Phytopathogenic fungi are able to overcome plant chemical defenses through
      detoxification reactions that are enzyme mediated. As a result of such
      detoxifications, the plant is quickly depleted of its most important antifungal
      metabolites and can succumb to pathogen attack. Understanding and predicting such
      detoxification pathways utilized by phytopathogenic fungi could lead to
      approaches to control plant pathogens. Towards this end, the inhibitory
      activities and metabolism of the cruciferous phytoalexins camalexin, brassinin,
      cyclobrassinin, and brassilexin by the phytopathogenic fungus Botrytis cinerea
      Pers. (teleomorph: Botryotinia fuckeliana) was investigated. Brassilexin was the
      most antifungal of the phytoalexins, followed by camalexin, cyclobrassinin and
      brassinin. Although B. cinerea is a species phylogenetically related to the
      phytopathogenic fungus Sclerotinia sclerotiorum (Lib) de Bary, contrary to S.
      sclerotiorum, detoxification of strongly antifungal phytoalexins occurred via
      either oxidative degradation or hydrolysis but not through glucosylation,
      suggesting that glucosyl transferases are not involved. A strongly antifungal
      bisindolylthiadiazole that B. cinerea could not detoxify was discovered, which
      resulted from spontaneous oxidative dimerization of 3-indolethiocarboxamide, a
      camalexin detoxification product.

PMID- 21176926
TI  - Recent progress in liquid chromatography-based separation and label-free
      quantitative plant proteomics.
AB  - Recent innovations in liquid chromatography-mass spectrometry (LC-MS)-based
      methods have facilitated quantitative and functional proteomic analyses of large
      numbers of proteins derived from complex samples without any need for protein or
      peptide labelling. Regardless of its great potential, the application of these
      proteomics techniques to plant science started only recently. Here we present an
      overview of label-free quantitative proteomics features and their employment for
      analysing plants. Recent methods used for quantitative protein analyses by MS
      techniques are summarized and major challenges associated with label-free LC-MS
      based approaches, including sample preparation, peptide separation,
      quantification and kinetic studies, are discussed. Database search algorithms and
      specific aspects regarding protein identification of non-sequenced organisms are
      also addressed. So far, label-free LC-MS in plant science has been used to
      establish cellular or subcellular proteome maps, characterize plant-pathogen
      interactions or stress defence reactions, and for profiling protein patterns
      during developmental processes. Improvements in both, analytical platforms
      (separation technology and bioinformatics/statistical analysis) and high
      throughput nucleotide sequencing technologies will enhance the power of this
      method.

PMID- 21176927
TI  - Tea prepared from Anastatica hirerochuntica seeds contains a diversity of
      antioxidant flavonoids, chlorogenic acids and phenolic compounds.
AB  - HPLC-PDA-MS(2) was used to identify phenolic and polyphenolic compounds in an
      herbal tea made from seeds of Anastatica hirerochuntica, a plant found in the
      Sahara-Arabian deserts and used to treat a variety of ailments. Twenty compounds
      comprising a series of flavone C- and O-linked glycosides, phenolic acids,
      chlorogenic acids and flavonols were identified or partially identified on the
      basis of co-chromatography with reference compounds and MS(2) and MS(3)
      fragmentation patterns. The flavones were the principal components, occurring as
      luteolin, apigenin and diosmetin conjugates. The antioxidant potential of
      individual compounds in Anastatica was assessed using HPLC with an on-line
      ABTS.(+) detection system. This revealed that 14 compounds exhibited antioxidant
      activity. The highest contribution to the antioxidant capacity of the tea, 56%,
      came from 3,4-dihydroxybenzoic acid and caffeoyl- and dicaffeoylquinic acids
      while 6-C-glucosides of luteolin and apigenin contributed 41%.

PMID- 21176928
TI  - Relationships between endometrial cytology and interval to first ovulation, and
      pregnancy in postpartum dairy cows in a single herd.
AB  - The objectives were to investigate the relationships between endometrial cytology
      (EC) and interval from calving to first ovulation, and pregnancy in dairy cows,
      and that between uterine fluid and EC. On day 25 postpartum, 39 dairy cows were
      grouped based on EC, as having low (<=8%) or high (>8%) polymorphonuclear cells
      (PMN), and the quantity of uterine fluid was assessed by ultrasound. The interval
      from calving to first ovulation was shorter in low, than in high PMN cows (32 vs.
      45 d). A greater proportion of cows with uterine fluid had high PMN (64% vs.
      21%), and the PMN increased from 14% to 34% as the quantity of uterine fluid
      increased. The mean interval from calving to ovulation was longer in primiparous
      cows with high PMN (49 d) compared to that of primiparous and multiparous cows
      with low PMN (28 and 29 d, respectively). Although the conception rate to first
      service at 92 d postpartum was not different between PMN groups, the cumulative
      pregnancy at 270 d tended to be higher in low than in high PMN (80% vs. 58%)
      multiparous cows. Also, cows that had uterine fluid on day 25 postpartum had a
      shorter interval from calving to pregnancy than those with no uterine fluid (161
      vs. 208 d). In conclusion, combining transrectal ultrasonography with endometrial
      cytology on day 25 postpartum has diagnostic value in the assessment of uterine
      inflammation.

PMID- 21176929
TI  - Effect of triple pelvic osteotomy on the proximal femoral geometry in dysplastic
      dogs.
AB  - Triple pelvic osteotomy (TPO) is one of the surgical procedures for use to try to
      reduce subsequent degenerative joint disease or modify the progress of hip
      dysplasia in young dogs. Joint force and pressure distribution were changed by
      this procedure. Therefore, the aim of this study was to find out whether the
      remodeling of proximal femur exists or not after TPO in dysplastic dogs. Ten
      femora from five young dysplastic mongrel dogs, treated unilaterally with TPO
      using 20 degrees  canine pelvic osteotomy plates, were used. One year after TPO,
      neck-proximal shaft angle, femoral head, neck, diaphyseal and mid-shaft
      diameters, total femoral, femoral neck axis, and intertrochanteric, femoral head
      offset lengths as well as the lengths from head center to lateral margin of
      greater trochanter and to proximal femoral axis were measured from the bone. The
      significant differences between treatment and control side were determined in
      Norberg angle, neck-proximal shaft angle, neck diameter, diaphyseal diameter, mid
      shaft diameter, length from head center to proximal femoral axis and femoral head
      offset length. In conclusion, although small number of cases was used, it was
      determined that the aforementioned variables are affected by TPO. So, these
      variables may be supply additional information about the changes to the joint
      following TPO in dysplastic dogs.

PMID- 21176930
TI  - [Cognitive rehabilitation in multiple sclerosis: a review of the literature].
AB  - INTRODUCTION: Cognitive impairment is now well-known in multiple sclerosis (MS).
      However, few rehabilitation interventions are proposed or really efficient.
      OBJECTIVES: To present a review of cognitive rehabilitation intervention research
      conducted in people with multiple sclerosis (MS), regarding different findings
      about episodic memory, working memory, attention and executive function disorders
      in MS. DATA SOURCES: A search of Medline (yield 20 papers) and of PsychInfo
      (yield 1 article), using combinations of the following terms: cognitive
      rehabilitation, multiple sclerosis, cognitive therapy, neuropsychological
      rehabilitation, in the title or in the abstract, from 1960 to March 2010,
      excluding animal studies. RESULTS: Episodic memory rehabilitation studies appear
      to be promising. Programs on working memory, attention and executive functions
      are in the very early phases. CONCLUSIONS: Results are encouraging and allow
      specific recommendations for future research about: (1) inclusion criteria, often
      not defined, (2) a specific baseline adapted to the program of rehabilitation,
      (3) a control measure regarding program efficiency and (4) a role for the
      psychologist (presence and advice during the program).

PMID- 21176931
TI  - A painless complete abdominal wall palsy with groin and thigh paresthesiae
      related to traffic accident injury.
AB  - INTRODUCTION: No case of complete unilateral abdominal wall palsy, occurring
      after a traffic accident, was found in the literature data. We report one case.
      CASE REPORT: A 32-year-old woman was treated for a large abdominal hernia by mesh
      prosthesis nine years after a traffic accident injury. Surgery led to an
      iatrogenic lesion of the right lateral femoral cutaneous nerve (LFCN). During the
      electrodiagnostic examination for the LFCN lesion, abdominal wall palsy was
      diagnosed. Analysis of the patient's history and clinical, electrophysiological,
      and imaging data revealed that this abdominal wall palsy was related to a tear of
      the T10 to L2 anterior roots, plexus or nerves, a consequence of the violent
      deceleration during the car crash. CONCLUSION: This report highlights the
      importance of clinical examination, electrodiagnosis and imaging in diagnosing
      abdominal wall palsy.

PMID- 21176932
TI  - Primary leiomyosarcoma of the inferior vena cava: a 2-institution analysis of
      outcomes.
AB  - BACKGROUND: Approximately 300 cases of leiomyosarcoma of the inferior vena cava
      (IVC) have been reported in the literature to date. In this study, we combined
      the experience from 2 institutions to provide additional clinical outcomes data.
      METHODS: We performed a retrospective analysis from 1984 to 2009 that included 17
      patients treated between the 2 institutions. Clinicopathologic data, surgical and
      adjuvant therapy, and survival outcomes were obtained. RESULTS: The median age of
      patients in the study was 48 years. The tumor location was infrarenal in 8
      patients, juxtarenal in 6, and suprahepatic in 2 patients; 7 patients had high
      grade tumors. All patients underwent complete resection; the IVC was repaired
      primarily in 5 patients, ligated in 5, and reconstructed with a prosthetic tube
      graft in 7 patients. There was no perioperative mortality; 6 patients had
      complications. Median follow-up was 49 months; median survival had not been
      reached when this paper was written. The 5-year overall and disease -free
      survival were 56% and 37%, respectively. Of the 17 patients, 10 experienced
      disease recurrence and underwent numerous treatment modalities for these
      recurrences. CONCLUSION: Aggressive resection of primary leiomyosarcoma of the
      IVC can be performed safely and result in long-term survival, irrespective of IVC
      management. Despite high recurrence rates, no consensus yet exists regarding
      adjuvant treatment.

PMID- 21176933
TI  - The necessity of hepatic vein reconstruction after resection of cranial part of
      the liver and major hepatic veins in cirrhotic patients.
AB  - BACKGROUND: The necessity of hepatic vein reconstruction (HVR) after resection of
      cranial part of the liver and major hepatic vein(s) in cirrhotic patients when
      residual liver is insufficient for a major hepatectomy remains unclear. METHODS:
      Fifty-two cirrhotic patients who underwent resection of cranial part of the liver
      and hepatic vein(s) for liver neoplasms were divided retrospectively into 3
      groups based on the volume of the congestive area of the remnant liver after
      hepatectomy: group A, 28 patients, the volume of the congestive area was <=20% of
      the residual liver volume and underwent no HVR; group B, 7 patients, the volume
      of the congestive area was >20% of residual liver volume and underwent no HVR;
      and group C, 17 patients, in whom HVR was performed (the volume of the congestive
      area was >20% of residual liver volume in 16 and <20% in 1). Background
      characteristics and postoperative results were compared between the groups.
      RESULTS: Although group C patients had a significantly longer operative time,
      their postoperative courses were similar to group A patients. Group B patients
      had a significantly longer postoperative hospital stay and a greater
      postoperative morbidity and 90-day mortality. No 90-day mortality ensued in the
      group A and C patients. CONCLUSION: In selected cirrhotic patients whose remnant
      liver is insufficient for major hepatectomy, HVR appears to be safe and desirable
      after resection of the cranial part of liver and hepatic vein when the volume of
      congestive area of liver remnant exceeds 20% of future residual liver volume.

PMID- 21176934
TI  - Clinical impact of a macroscopically complete resection of colorectal cancer with
      peritoneal carcinomatosis.
AB  - BACKGROUND: So far, few reports have focused on the clinicopathological features
      and patterns of recurrence after a complete resection of peritoneal
      carcinomatosis (PC) of colorectal origin. The purpose of the present study was to
      show the clinicopathological features of a macroscopically complete resected
      tumor and the pattern of recurrence after the curative resection of colorectal
      PC. METHODS: In 153 patients with colorectal PC, 31 patients who underwent a
      complete resection of a synchronous primary lesion of a colorectal PC between
      1998 and 2007 were assessed retrospectively. RESULTS: Clinicopathological
      differences were observed in the tumor location, presence of extraperitoneal
      metastases, extent of PC, and presence of lymph node metastases between a
      macroscopically complete resection and noncomplete resection patients (P = .045,
      P < .0001, P < .001, and P = .039, respectively). Tumor recurrence after the
      complete resection of colorectal PC was observed in 24 patients (77.4%). The 5
      year survival rate after complete resection was 36.0%. The survival rate in the
      macroscopically complete resection group was higher than in the incomplete
      resection group (P < .001). The 5-year intra- and extraperitoneal recurrence
      survival rates were 63.9% and 33.8%, respectively. No significant
      clinicopathological factors affected intraperitoneal recurrence-free survival.
      Conversely, a univariate analysis using the log-rank test revealed that extended
      PC and presence of lymph node metastases were poor factors affecting
      extraperitoneal recurrence (P = .009 and P = .023, respectively). Eleven of 31
      patients survived for 5 years after resection. Two of the 4 patients with liver
      metastases had received a hepatectomy. CONCLUSION: Although the 5-year survival
      rate after a macroscopically complete resection for colorectal PC approached
      36.0%, 77.4% of patients developed intra- and extraperitoneal recurrence.
      Extended PC and presence of lymph node metastases were poor factors affecting
      extraperitoneal recurrence.

PMID- 21176935
TI  - Early cancer-related death after resection of hepatocellular carcinoma.
AB  - BACKGROUND: Surgeons have attempted to prevent early cancer-related death after
      resection of hepatocellular carcinoma to identify risk factors associated with
      early death from hepatocellular carcinoma recurrence after liver resection.
      METHODS: The study group comprised 350 patients who had undergone liver resection
      for hepatocellular carcinoma between 1997 and 2007. The preoperative risk factors
      for early death from intrahepatic recurrence (within 1 year after resection) were
      evaluated. RESULTS: Fourteen (4%) patients died of intrahepatic recurrence in the
      first year after resection. Multivariate analyses identified the following risk
      factors for early cancer-related death: multiple tumors (odds ratio 10.4; 95%
      confidence interval, 2.42-44.3; P = .002), vascular invasion (odds ratio 10.1;
      95% confidence interval 2.07-50; P = .004), serum alpha-fetoprotein level >20
      ng/mL (odds ratio 9.52; 95% confidence interval 1.0--84.2; P = .043), and tumor
      size >=50 mm (odds ratio 4.80; 95% confidence interval 1.06-21.9; P = .042). Each
      of these factors was assigned a score of 1 point, and an algorithm was developed
      to predict the risk of early death. Outcomes did not differ significantly between
      patients with 3 or 4 points (P = .48) or between those with 1 or 2 points (P =
      .49). Patients who underwent liver resection could be stratified into the
      following distinct groups according to the point score and the associated 1-year
      survival rate and median survival (shown respectively): 0 points, 99%, and not
      yet; 1 or 2 points, 96%, and 68 months; and 3 or 4 points, 50%, and 12 months) (P
      < .0001). CONCLUSION: Even if hepatocellular carcinoma is resectable, patients
      with a score of 3 or 4 points may not be good candidates for liver resection.

PMID- 21176936
TI  - Phage displayed peptides recognizing porcine aminopeptidase N inhibit
      transmissible gastroenteritis coronavirus infection in vitro.
AB  - Porcine aminopeptidase N (pAPN) is a cellular receptor of transmissible
      gastroenteritis virus (TGEV), a porcine coronavirus. Interaction between the
      spike (S) protein of TGEV and pAPN initiates cell infection. Small molecules,
      especially peptides are an expanding area for therapy or diagnostic assays for
      viral diseases. Here, the peptides capable of binding the pAPN were, for the
      first time, identified by biopanning using a random 12-mer peptide library to the
      immobilized protein. Three chemically synthesized peptides recognizing the pAPN
      showed effective inhibition ability to TGEV infection in vitro. A putative TxxF
      motif was identified in the S protein of TGEV. Phages bearing the specific
      peptides interacted with the pAPN in ELISA. 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide (MTT) assays confirmed the protective effect of the
      peptides on cell infection by TGEV. Moreover, the excellent immune responses in
      mice induced by the identified phages provided the possibility to develop novel
      phage-based vaccines.

PMID- 21176937
TI  - The HTLV-1 hbz antisense gene indirectly promotes tax expression via down
      regulation of p30(II) mRNA.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) basic leucine zipper factor (HBZ) is
      transcribed from the antisense genomic DNA strand and functions differently in
      its RNA and protein forms. To distinguish between the roles of hbz mRNA and HBZ
      protein, we generated mutants in a proviral clone that specifically disrupt the
      hbz gene product. A proviral clone with a splice acceptor mutation that disrupts
      expression of the predominant hbz mRNA resulted in lower levels of tax mRNA.
      Heterologous hbz expression restored Tax activity in cells expressing this mutant
      clone. In contrast, proviral mutants that disrupt HBZ protein did not affect
      levels of tax mRNA. Expression of hbz resulted in lower levels of p30(II) mRNA.
      Mutation of p30(II) overcame the effects of the splice acceptor mutation of hbz,
      and restored tax expression. Thus, there is a complex interplay of viral
      regulatory proteins controlling levels of HTLV-1 gene expression.

PMID- 21176938
TI  - Properties of an equine herpesvirus 1 mutant devoid of the internal inverted
      repeat sequence of the genomic short region.
AB  - The 150 kbp genome of equine herpesvirus-1 (EHV-1) is composed of a unique long
      (UL) region and a unique short (Us) segment, which is flanked by identical
      internal and terminal repeat (IR and TR) sequences of 12.7 kbp. We constructed an
      EHV-1 lacking the entire IR (vL11DeltaIR) and showed that the IR is dispensable
      for EHV-1 replication but that the vL11DeltaIR exhibits a smaller plaque size and
      delayed growth kinetics. Western blot analyses of cells infected with vL11DeltaIR
      showed that the synthesis of viral proteins encoded by the immediate-early,
      early, and late genes was reduced at immediate-early and early times, but by late
      stages of replication reached wild type levels. Intranasal infection of CBA mice
      revealed that the vL11DeltaIR was significantly attenuated as mice infected with
      the vL11DeltaIR showed a reduced lung viral titer and greater ability to survive
      infection compared to mice infected with parental or revertant virus.

PMID- 21176939
TI  - Inactivation of bacteriophage MS2 upon exposure to very low concentrations of
      chlorine dioxide.
AB  - This study investigates the effects of very low concentrations of ClO(2) applied
      in drinking water practice on the inactivation of bacteriophage MS2.
      Concentrations of 0.5 mg/L, 0.1 mg/L and 0.02 mg/L ClO(2) inactivated at least 5
      log units of MS2 after an exposure time of approximately 20, 50 and 300 min
      respectively. When the ClO(2) concentration was as low as 0.005 mg/L,
      inactivation of 1 log unit MS2 was observed after 300 min exposure. Increasing
      the contact time to 24 h did not increase the inactivation any further. Non
      linear inactivation kinetics (tailing) were observed for all conditions tested.
      Repeated addition of MS2 to the reactor showed that tailing was not caused by a
      reduction of the biocidal effect of ClO(2) during disinfection. The Modified
      Chick-Watson, the Efficiency Factor Hom (EFH) model and the Modified Cerf model,
      a modification of the two-fraction Cerf model, were fitted to the non-linear
      inactivation curves. Both the EFH and the modified Cerf model did fit accurately
      to the inactivation data of all experiments. The good fit of the Modified Cerf
      model supports the hypothesis of the presence of two subpopulations. Our study
      showed that ClO(2) is an effective disinfectant against model organism MS2, also
      at the low concentrations applied in water treatment practice. The inactivation
      kinetics followed a biphasic pattern due to the presence of a more ClO(2)
      resistant subpopulation of MS2 phages, either caused by population heterogeneity
      or aggregation/adhesion of MS2.

PMID- 21176940
TI  - Adsorptive removal of an acid dye by lignocellulosic waste biomass activated
      carbon: equilibrium and kinetic studies.
AB  - Chemically prepared activated carbon material derived from palm flower was used
      as adsorbent for removal of Amido Black dye in aqueous solution. Batch adsorption
      studies were performed for the removal of Amido Black 10B (AB10B), a di-azo acid
      dye from aqueous solutions by varying the parameters like initial solution pH,
      adsorbent dosage, initial dye concentration and temperature with three different
      particle sizes such as 100 MUm, 600 MUm and 1000 MUm. The zero point charge was
      pH 2.5 and the maximum adsorption occurred at the pH 2.3. Experimental data were
      analyzed by model equations such as Langmuir, Freundlich and Temkin isotherms and
      it was found that the Freundlich isotherm model best fitted the adsorption data
      and the Freundlich constants varied from (K(F)) 1.214, 1.077 and 0.884 for the
      three mesh sizes. Thermodynamic parameters such as DeltaG, DeltaH and DeltaS were
      also calculated for the adsorption processes and found that the adsorption
      process is feasible and it was the endothermic reaction. Adsorption kinetics was
      determined using pseudo first-order, pseudo second-order rate equations and also
      Elovich model and intraparticle diffusion models. The results clearly showed that
      the adsorption of AB10B onto lignocellulosic waste biomass from palm flower
      (LCBPF) followed pseudo second-order model, and the pseudo second-order rate
      constants varied from 0.059 to 0.006 (g mg(-1)min) by varying initial adsorbate
      concentration from 25 mg L(-1) to 100 mg L(-1). Analysis of the adsorption data
      confirmed that the adsorption process not only followed intraparticle diffusion
      but also by the film diffusion mechanism.

PMID- 21176941
TI  - Immunosuppression in the infaunal bivalve Scrobicularia plana environmentally
      exposed to mercury and association with its accumulation.
AB  - This study aimed to test the hypothesis whether mercury (Hg) activates or
      suppresses inappropriately the immunity of the bivalve Scrobicularia plana
      inhabiting a Hg contaminated area (Laranjo basin, Ria de Aveiro, Portugal).
      Immunity endpoints, as well as lipid peroxidation (LPO) as a sign of damage, were
      evaluated in parallel with total Hg burden. Bivalves from both moderately (MO)
      and highly (HI) contaminated sites displayed higher haemolymph Hg load and
      reduced plasma agglutination. Increased haemocytes density and decreased
      phagocytosis were observed at HI, whereas increased oxidative burst activity
      (OBA) was observed at MO, pointing out that the immunotoxicity is a result of Hg
      direct contact involving no ROS intervention. OBA observed at MO was
      concomitantly associated to peroxidative damage as depicted by LPO increase in
      haemocytes and haemolymph plasma. Thus, S. plana can be suggested as a suitable
      bioindicator of metal pollution in coastal areas on the basis of Hg
      bioaccumulation and immunotoxicity responses.

PMID- 21176942
TI  - The degradation of chlorpyrifos and diazinon in aqueous solution by ultrasonic
      irradiation: effect of parameters and degradation pathway.
AB  - In this paper, elimination of two types of organophosphorus pesticides (OPPs),
      chlorpyrifos and diazinon spiked in aqueous solution by ultrasonic irradiation
      was investigated. Results showed that chlorpyrifos and diazinon could be
      effectively and rapidly degraded by ultrasonic irradiation, and the degradation
      of both pesticides was strongly influenced by ultrasonic power, temperature and
      pH value. Furthermore, two and seven products for the degradation of chlorpyrifos
      and diazinon formed during ultrasonic irradiation have been identified by gas
      chromatography-mass spectrometry, respectively. The hydrolysis, oxidation,
      hydroxylation, dehydration and decarboxylation were deduced to contribute to the
      degradation reaction and the degradation pathway for each pesticide under
      ultrasonic irradiation was proposed. Finally, the toxicity evaluation indicated
      that the toxicity decreased for diazinon solution after ultrasonic irradiation,
      but it increased for chlorpyrifos solution. The detoxification of OPPs by
      ultrasonic irradiation was discriminative.

PMID- 21176943
TI  - Bioaccumulation of pollutants in the zebra mussel from hazardous industrial waste
      and evaluation of spatial distribution using GAMs.
AB  - In the Flix Reservoir (Ebro River, Spain), ca. 300,000tons of industrial waste
      were dumped because of the activity of a factory plant in Flix. Within the
      recovery program implemented, this exceptional situation provides a unique
      opportunity to test the value of zebra mussel as sentinel organism. Ten metal
      concentrations were measured in mussels from different sites to assess spatial
      redistribution of metals and bioavailability to the food web. Our results showed
      an important metal uptake by mussels; metal concentrations (except As) measured
      in impacted sites were up to 10 times higher than in control sites, and Mn and Hg
      exceeded several times the levels previously reported for polluted waters.
      Concentrations increased downstream showing the metal mobilization from polluted
      sediments in Flix Reservoir. The higher metal concentrations measured in zebra
      mussel individuals clearly indicated their bioavailability to the food web,
      allowing the toxics transfer to predators and occasionally to humans. Thus, zebra
      mussel is a valuable sentinel organism to identify highly polluted waters,
      transport routes and trophic transfer.

PMID- 21176944
TI  - Health impacts associated with the implementation of a national petrol-lead phase
      out program (PLPOP): evidence from Taiwan between 1981 and 2007.
AB  - BACKGROUND AND OBJECTIVE: In 1981, a petrol-lead phase-out program (PLPOP) was
      launched in Taiwan for the abatement of environmental lead emissions. The present
      study was set out to examine whether the reduction of environmental lead
      emissions would result in the decrease in mortality rates of various diseases
      based on national data between 1981 and 2007. METHOD: The national mortality data
      were obtained from the Office of Statistics of the Taiwan Department of Health
      (Taiwan DOH). Standardized mortality ratios (SMRs) were calculated based on 2000
      WHO world standard population. Gasoline consumptions were obtained from the
      Bureau of Energy. RESULTS: The mean blood lead levels (BLLs) had decreased
      dramatically from approximately 20.14MUg/dl in the leaded petrol phase to 3MUg/dl
      or lower in the unleaded petrol phase. From 1981 to 2007, the mortality (per
      100,000 people) was decreased from 146.2 to 43.8 for cerebrovascular disease,
      from 85.3 to 44.4 for heart disease, from 35.4 to 6.6 for hypertensive disease,
      from 21.3 to 17.3 for nephrosis, and from 810.2 to 491.6 for all causes. By
      taking the confounders (including economic growth rate, per capita income,
      tobacco consumption, and medical resources) into account, the decreases in SMRs
      for all causes, cerebrovascular disease, and nephrosis were found to be highly
      correlated with the decrease in petrol lead emissions (p-values=0.001, <0.001,
      0.020, respectively). CONCLUSION: Our results clearly show that the
      implementation of the PLPOP was associated with a decline in mortality rates in
      several diseases that have been associated with lead exposure, even after
      adjustment for a number of relevant confounders.

PMID- 21176945
TI  - Biogeochemical factors influencing net mercury methylation in contaminated
      freshwater sediments from the St. Lawrence River in Cornwall, Ontario, Canada.
AB  - The activity of various anaerobic microbes, including sulfate reducers (SRB),
      iron reducers (FeRP) and methanogens (MPA) has been linked to mercury methylation
      in aquatic systems, although the relative importance of each microbial group in
      the overall process is poorly understood in natural sediments. The present study
      focused on the biogeochemical factors (i.e. the relative importance of various
      groups of anaerobic microbes (FeRP, SRB, and MPA) that affect net
      monomethylmercury (MMHg) formation in contaminated sediments of the St. Lawrence
      River (SRL) near Cornwall (Zone 1), Ontario, Canada. Methylation and
      demethylation potentials were measured separately by using isotope-enriched
      mercury species ((200)Hg(2+) and MM(199)Hg(+)) in sediment microcosms treated
      with specific microbial inhibitors. Sediments were sampled and incubated in the
      dark at room temperature in an anaerobic chamber for 96h. The potential
      methylation rate constants (K(m)) and demethylation rates (K(d)) were found to
      differ significantly between microcosms. The MPA-inhibited microcosm had the
      highest potential methylation rate constant (0.016d(-1)), whereas the two SRB
      inhibited microcosms had comparable potential methylation rate constants (0.003d(
      1) and 0.002d(-1), respectively). The inhibition of methanogens stimulated net
      methylation by inhibiting demethylationand by stimulating methylation along with
      SRB activity. The inhibition of both methanogens and SRB was found to enhance the
      iron reduction rates but did not completely stop MMHg production. The strong
      positive correlation between K(m) and Sulfate Reduction Rates (SRR) and between
      K(d) and Methane Production Rates (MPR) supports the involvement of SRB in Hg
      methylation and MPA in MMHg demethylation in the sediments. In contrast, the
      strong negative correlation between K(d) and Iron Reduction Rates (FeRR) shows
      that the increase in FeRR corresponds to a decrease in demethylation, indicating
      that iron reduction may influence net methylation in the SLR sediments by
      decreasing demethylation rather than favouring methylation.

PMID- 21176946
TI  - Fracture strength of temporary fixed partial dentures: CAD/CAM versus directly
      fabricated restorations.
AB  - OBJECTIVES: This study aimed at investigating the influence of fabrication
      method, storage condition and material on the fracture strength of temporary 3
      unit fixed partial dentures (FPDs). METHODS: A CrCo-alloy master model with a 3
      unit FPD (abutment teeth 25 and 27) was manufactured. The master model was
      scanned and the data set transferred to a CAD/CAM unit (Cercon Brain Expert,
      Degudent, Hanau, Germany). Temporary 3-unit bridges were produced either by
      milling from pre-fabricated blanks (Trim, Luxatemp AM Plus, Cercon Base PMMA) or
      by direct fabrication (Trim, Luxatemp AM Plus). 10 FPDs per experimental group
      were subjected either to water storage at 37  degrees C for 24h and 3 months,
      respectively, or thermocycled (TC, 5000*, 5-55  degrees C, 1 week). Maximum force
      at fracture (Fmax) was determined in a 3-point bending test at 200 mm/min. Data
      was analyzed using parametric statistics (alpha = 5%). RESULTS: Fmax values
      ranged from 138.5 to 1115.5N. FPDs, which were CAD/CAM fabricated, showed a
      significant higher Fmax compared to the directly fabricated bridges (p < 0.05).
      TC significantly affected Fmax for Luxatemp (p < 0.05) but not for the PMMA based
      materials (p > 0.05). CAD/CAM milled FPDs made of Luxatemp showed significantly
      higher Fmax values compared to Trim and Cercon Base PMMA (p < 0.05).
      SIGNIFICANCE: CAD/CAM fabricated FPDs exhibit a higher mechanical strength
      compared to directly fabricated FPDs, when manufactured of the same material.
      Composite based materials seem to offer clear advantages versus PMMA based
      materials and should, therefore, be considered for CAD/CAM fabricated temporary
      restorations.

PMID- 21176947
TI  - Effect of ball milling on structures and properties of dispersed-type dental
      amalgam.
AB  - OBJECTIVES: The purpose of the present study was to investigate the effect of
      ball milling on the initial mercury vapor release rate and mechanical properties
      such as compressive strength, diametral tensile strength and creep value, of the
      dispersed-type dental amalgam, and comparison was made with respect to two
      commercial amalgam alloys. METHODS: Ball milling was employed to modify the
      configuration of the originally spherical-shaped Ag-Cu-Pd dispersant alloy
      particles. Improvement in mechanical properties while maintaining a low early
      stage mercury vapor release rate of the amalgam is attempted. RESULTS: The
      experimental results show that the amalgam (AmB10) which was made from Ag-Cu-Pd
      dispersant alloy particles that were ball-milled for 10 min and heat-treated at
      300  degrees C for 2 days exhibited a low initial mercury vapor release rate of
      69 pg/mm(2)/s, which was comparable with that of commercial amalgam alloy Tytin
      (68 pg/mm(2)/s), and was lower than that of Dispersalloy (73 pg/mm(2)/s). As for
      mechanical properties, amalgam AmB10 exhibited the highest 1h compressive
      strength (228 MPa), which was higher than that of commercial amalgam alloy
      Dispersalloy by 72%; while its 24h diametral tensile strength was also the
      highest (177 MPa), and was higher than that of Dispersalloy by 55%. Furthermore,
      the creep value of the amalgams made from Ag-Cu-Pd alloy particles with 10 min
      ball-milling and heat treatment at 300  degrees C for 2 days was measured to be
      0.12%, which was about 20% that of Dispersalloy. SIGNIFICANCE: It is found that
      ball milling of the dispersant Ag-Cu-Pd alloy particles for 10 min was able to
      modify the configuration of the alloy particles into irregular-shapes.
      Subsequently, heat treatment at 300  degrees C significantly lowered the initial
      mercury vapor release rate, increased its 1h compressive strength and 1h
      diametral tensile strength, and lowered its creep value.

PMID- 21176948
TI  - Wormy mothers, healthy babies: case closed or conundrum?

PMID- 21176949
TI  - Rituximab maintenance for 2 years in patients with high tumour burden follicular
      lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised
      controlled trial.
AB  - BACKGROUND: Patients with follicular lymphoma can have long survival times, but
      disease progression typically occurs 3-5 years after initial treatment. We
      assessed the potential benefit of 2 years of rituximab maintenance after first
      line treatment in patients with follicular lymphoma receiving a rituximab plus
      chemotherapy regimen. METHODS: The randomised, open-label PRIMA study was
      undertaken in 223 centres in 25 countries. 1217 patients with previously
      untreated follicular lymphoma needing systemic therapy received one of three non
      randomised immunochemotherapy induction regimens used in routine practice. 1019
      patients achieving a complete or partial response were then randomly assigned to
      receive 2 years of rituximab maintenance therapy (375 mg/m(2) every 8 weeks) or
      observation. Treatment was assigned equally by centralised block randomisation,
      stratified by induction regimen, response, region, and centre. Neither the
      participants nor those giving the interventions, assessing outcomes, and
      analysing data were masked to group assignments. The primary endpoint was
      progression-free survival (PFS). Analysis was by intention to treat. This trial
      is registered with ClinicalTrials.gov, number NCT00140582. FINDINGS: 505 patients
      were assigned to rituximab maintenance and 513 to observation (one patient died
      during randomisation). With a median follow-up of 36 months (IQR 30-42), PFS was
      74.9% (95% CI 70.9-78.9) in the rituximab maintenance group (130 patients
      progressed) and 57.6% (53.2-62.0) in the observation group (218 progressed;
      hazard ratio [HR] 0.55, 95% CI 0.44-0.68, p<0.0001). 2 years after randomisation,
      361 patients (71.5%) in the rituximab maintenance group were in complete or
      unconfirmed complete response versus 268 (52.2%) in the observation group
      (p=0.0001). Overall survival did not differ significantly between groups (HR
      0.87, 95% CI 0.51-1.47). Grade 3 and 4 adverse events were recorded in 121
      patients (24%) in the rituximab maintenance group and 84 (17%) in the observation
      group (risk ratio 1.46, 95% CI 1.14-1.87; p=0.0026). Infections (grades 2-4) were
      the most common adverse event, occurring in 197 (39%) and 123 (24%) patients,
      respectively (risk ratio 1.62, 95% CI 1.35-1.96; p<0.0001). INTERPRETATION: 2
      years of rituximab maintenance therapy after immunochemotherapy as first-line
      treatment for follicular lymphoma significantly improves PFS. FUNDING: Groupe
      d'Etude des Lymphomes de l'Adulte (GELA) and F Hoffmann-La Roche.

PMID- 21176951
TI  - Rituximab maintenance in follicular lymphoma: PRIMA.

PMID- 21176950
TI  - Effect of single-dose anthelmintic treatment during pregnancy on an infant's
      response to immunisation and on susceptibility to infectious diseases in infancy:
      a randomised, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Helminth infections affect the human immune response. We investigated
      whether prenatal exposure to and treatment of maternal helminth infections
      affects development of an infant's immune response to immunisations and unrelated
      infections. METHODS: In this randomised, double-blind, placebo-controlled trial,
      we enrolled 2507 women in the second or third trimester of pregnancy who were
      planning to deliver in Entebbe General Hospital, Entebbe, Uganda. With a computer
      generated random number sequence in blocks of 100, we assigned patients to 440 mg
      albendazole and 40 mg/kg praziquantel (n=628), 440 mg albendazole and a
      praziquantel-matching placebo (n=625), 40 mg/kg praziquantel and an albendazole
      matching placebo (n=626), or an albendazole-matching placebo and praziquantel
      matching placebo (n=628). All participants and hospital staff were masked to
      allocation. Primary outcomes were immune response at age 1 year to BCG, tetanus,
      and measles immunisation; incidence of infectious diseases during infancy; and
      vertical HIV transmission. Analysis was by intention-to-treat. This trial is
      registered, number ISRCTN32849447. FINDINGS: Data were available at delivery for
      2356 women, with 2345 livebirths; 2115 (90%) of liveborn infants remained in
      follow-up at 1 year of age. Neither albendazole nor praziquantel treatments
      affected infant response to BCG, tetanus, or measles immunisation. However, in
      infants of mothers with hookworm infection, albendazole treatment reduced
      interleukin-5 (geometric mean ratio 0.50, 95% CI 0.30-0.81, interaction p=0.02)
      and interleukin-13 (0.52, 0.34-0.82, 0.0005) response to tetanus toxoid. The rate
      per 100 person-years of malaria was 40.9 (95% CI 38.3-43.7), of diarrhoea was
      134.1 (129.2-139.2), and of pneumonia was 22.3 (20.4-24.4). We noted no effect on
      infectious disease incidence for albendazole treatment (malaria [hazard ratio
      0.95, 95% CI 0.79-1.14], diarrhoea [1.06, 0.96-1.16], pneumonia [1.11, 0.90
      1.38]) or praziquantel treatment (malaria [1.00, 0.84-1.20], diarrhoea [1.07,
      0.98-1.18], pneumonia [1.00, 0.80-1.24]). In HIV-exposed infants, 39 (18%) were
      infected at 6 weeks; vertical transmission was not associated with albendazole
      (odds ratio 0.70, 95% CI 0.35-1.42) or praziquantel (0.60, 0.29-1.23) treatment.
      INTERPRETATION: These results do not accord with the recently advocated policy of
      routine antenatal anthelmintic treatment, and the value of such a policy may need
      to be reviewed. FUNDING: Wellcome Trust.

PMID- 21176952
TI  - Impact of hydrotalcite deposition on biogeochemical processes in a shallow
      tropical bay.
AB  - The biogeochemistry of a tropical shoal bay (Melville Bay, Australia) impacted by
      the effluent release, precipitation, and deposition of hydrotalcite from an
      alumina refinery was studied in both wet and dry seasons. Within the deposition
      zone, sulfate reduction dominated benthic carbon cycling accounting for ~100% of
      total microbial activity, with rates greater than those measured in most other
      marine sediments. These rapid rates of anoxic metabolism resulted in high rates
      of sulfide and ammonium production and low C:S ratios, implying significant
      preservation of S in stable sulfide minerals. Rates of total microbial activity
      were significantly less in control sediments of equivalent grain size, where
      sulfate reduction accounted for ~50% of total benthic metabolism. Rates of
      planktonic carbon cycling overlying the deposition zone were also greater than
      those measured in the control areas of southern Melville Bay. At the sediment
      surface, productive algal and cyanobacterial mats helped stabilize the sediment
      surface and oxidize sulfide to sulfate to maintain a fully oxygenated water
      column overlying the impacted zone. The mats utilized a significant fraction of
      dissolved inorganic N and P released from the sea bed; some nutrients escaped to
      the water-column such that benthic regeneration of NH4+ and PO43- accounted for
      100% and 42% of phytoplankton requirements for N and P, respectively. These
      percentages are high compared to other tropical coastal environments and indicate
      that benthic nutrient recycling may be a significant factor driving water-column
      production overlying the deposition zone. With regard to remediation, it is
      recommended that the sea bed not be disturbed as attempts at removal may result
      in further environmental problems and would require specific assessment of the
      proposed removal process.

PMID- 21176953
TI  - Cellular transduction gradients via vapor-deposited polymer coatings.
AB  - Spatiotemporal control of gene delivery, particularly signaling gradients, via
      biomaterials poses significant challenges because of the lack of efficient
      delivery systems for therapeutic proteins and genes. This challenge was addressed
      by using chemical vapor deposition (CVD) polymerization in a counterflow set-up
      to deposit copolymers bearing two reactive chemical gradients. FTIR spectroscopy
      verified the formation of compositional gradients. Adenovirus expressing a
      reporter gene was biotinylated and immobilized using the VBABM method (virus
      biotin-avidin-biotin-materials). Sandwich ELISA confirmed selective attachment of
      biotinylated adenovirus onto copolymer gradients. When cultured on the adenovirus
      gradients, human gingival fibroblasts exhibited asymmetric transduction with full
      confluency. Importantly, gradient transduction occurred in both lateral
      directions, thus enabling more advanced delivery studies that involve gradients
      of multiple therapeutic genes.

PMID- 21176954
TI  - Multifunctional hollow nanoparticles based on graft-diblock copolymers for
      doxorubicin delivery.
AB  - This article reports a flexible hollow nanoparticles, self-assembling from poly(N
      vinylimidazole-co-N-vinylpyrrolidone)-g-poly(d,l-lactide) graft copolymers and
      methoxyl/functionalized-PEG-PLA diblock copolymers, as an anticancer drug
      doxorubicin (Dox) carrier for cancer targeting, imaging, and cancer therapy. This
      multifunctional hollow nanoparticle exhibited a specific on-off switch drug
      release behavior, owning to the pH-sensitive structure of imidazole, to release
      Dox in acidic surroundings (intracellular endosomes) and to capsulate Dox in
      neutral surroundings (blood circulation or extracellular matrix). Imaging by
      SPECT/CT shows that nanoparticle conjugated with folic acids ensures a high
      intratumoral accumulation due to the folate-binding protein (FBP)-binding effect.
      In vivo tumor growth inhibition shows that nanoparticles exhibited excellent
      antitumor activity and a high rate of apoptosis in cancer cells. After 80-day
      treatment course of nanoparticles, it did not appreciably cause heart, liver and
      kidney damage by inactive Dox or polymeric materials. The results indicate that
      the flexible carriers with an on-off switched drug release may be allowed to
      accurately deliver to targeted tumors for cancer therapy.

PMID- 21176955
TI  - Polyethylene glycol modified, cross-linked starch-coated iron oxide nanoparticles
      for enhanced magnetic tumor targeting.
AB  - While successful magnetic tumor targeting of iron oxide nanoparticles has been
      achieved in a number of models, the rapid blood clearance of magnetically
      suitable particles by the reticuloendothelial system (RES) limits their
      availability for targeting. This work aimed to develop a long-circulating
      magnetic iron oxide nanoparticle (MNP) platform capable of sustained tumor
      exposure via the circulation and, thus, potentially enhanced magnetic tumor
      targeting. Aminated, cross-linked starch (DN) and aminosilane (A) coated MNPs
      were successfully modified with 5 kDa (A5, D5) or 20 kDa (A20, D20) polyethylene
      glycol (PEG) chains using simple N-Hydroxysuccinimide (NHS) chemistry and
      characterized. Identical PEG-weight analogues between platforms (A5 & D5, A20 &
      D20) were similar in size (140-190 nm) and relative PEG labeling (1.5% of surface
      amines - A5/D5, 0.4% - A20/D20), with all PEG-MNPs possessing magnetization
      properties suitable for magnetic targeting. Candidate PEG-MNPs were studied in
      RES simulations in vitro to predict long-circulating character. D5 and D20
      performed best showing sustained size stability in cell culture medium at 37 
      degrees C and 7 (D20) to 10 (D5) fold less uptake in RAW264.7 macrophages when
      compared to previously targeted, unmodified starch MNPs (D). Observations in
      vitro were validated in vivo, with D5 (7.29 h) and D20 (11.75 h) showing much
      longer half-lives than D (0.12 h). Improved plasma stability enhanced tumor MNP
      exposure 100 (D5) to 150 (D20) fold as measured by plasma AUC(0-infinity).
      Sustained tumor exposure over 24 h was visually confirmed in a 9L-glioma rat
      model (12 mg Fe/kg) using magnetic resonance imaging (MRI). Findings indicate
      that a polyethylene glycol modified, cross-linked starch-coated MNP is a
      promising platform for enhanced magnetic tumor targeting, warranting further
      study in tumor models.

PMID- 21176956
TI  - Modulus-driven differentiation of marrow stromal cells in 3D scaffolds that is
      independent of myosin-based cytoskeletal tension.
AB  - Proliferation and differentiation of cells are known to be influenced by the
      physical properties of the extracellular environment. Previous studies examining
      biophysics underlying cell response to matrix stiffness utilized a two
      dimensional (2D) culture format, which is not representative of the three
      dimensional (3D) tissue environment in vivo. We report on the effect of 3D matrix
      modulus on human bone marrow stromal cell (hBMSC) differentiation. hBMSCs
      underwent osteogenic differentiation in poly(ethylene glycol) hydrogels of all
      modulus (300-fold modulus range, from 0.2 kPa to 59 kPa) in the absence of
      osteogenic differentiation supplements. This osteogenic differentiation was
      modulus-dependent and was enhanced in stiffer gels. Osteogenesis in these
      matrices required integrin-protein ligation since osteogenesis was inhibited by
      soluble Arginine-Glycine-Aspartate-Serine peptide, which blocks integrin
      receptors. Immunostained images revealed lack of well-defined actin filaments and
      microtubules in the encapsulated cells. Disruption of mechanosensing elements
      downstream of integrin binding that have been identified from 2D culture such as
      actin filaments, myosin II contraction, and RhoA kinase did not abrogate hBMSC
      material-driven osteogenic differentiation in 3D. These data show that increased
      hydrogel modulus enhanced osteogenic differentiation of hBMSCs in 3D scaffolds
      but that hBMSCs did not use the same mechanosensing pathways that have been
      identified in 2D culture.

PMID- 21176958
TI  - WITHDRAWN: Therapeutic efficacy of focal adhesion kinase downregulation in REH
      cells by RNA interference.
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- 21176957
TI  - Role of secretory granules in inositol 1,4,5-trisphosphate-dependent Ca(2+)
      signaling: from phytoplankton to mammals.
AB  - The majority of secretory cell calcium is stored in secretory granules that serve
      as the major IP(3)-dependent intracellular Ca(2+) store. Even in unicellular
      phytoplankton secretory granules are responsible for the IP(3)-induced Ca(2+)
      release that triggers exocytosis. The number of secretory granules in the cell is
      directly related not only to the magnitude of IP(3)-induced Ca(2+) release, which
      accounts for the majority of the IP(3)-induced cytoplasmic Ca(2+) release in
      neuroendocrine cells, but also to the IP(3) sensitivity of the cytoplasmic IP(3)
      receptor (IP(3)R)/Ca(2+) channels. Moreover, secretory granules contain the
      highest IP(3)R concentrations and the largest amounts of IP(3)Rs in any
      subcellular organelles in neuroendocrine cells. Secretory granules from
      phytoplankton to mammals contain large amounts of polyanionic molecules,
      chromogranins being the major molecules in mammals, in addition to acidic
      intragranular pH and high Ca(2+) concentrations. The polyanionic molecules
      undergo pH- and Ca(2+)-dependent conformational changes that serve as a molecular
      basis for condensation-decondensation phase transitions of the intragranular
      matrix. Likewise, chromogranins undergo pH- and Ca(2+)-dependent conformational
      changes with increased exposure of the structure and increased interactions with
      Ca(2+) and other granule components at acidic pH. The unique physico-chemical
      properties of polyanionic molecules appear to be at the center of biogenesis, and
      physiological functions of secretory granules in living organisms from primitive
      to advanced species.

PMID- 21176959
TI  - Increased HDAC1 deposition at hematopoietic promoters in AML and its association
      with patient survival.
AB  - Epigenetic changes play a crucial role in leukemogenesis. HDACs are frequently
      recruited to target gene promoters by balanced translocation derived oncogenic
      fusion proteins. As important epigenetic effector mechanisms, histone
      deacetylases (HDAC) have emerged as potential therapeutic targets. However, the
      patterns of HDAC1 localization and the role of HDACs in leukemia pathogenesis
      remain to be elucidated. Using ChIP-Chip analyses we analyzed HDAC1 deposition
      patterns at more than 10,000 gene promoters in a large cohort of leukemia
      patients and CD34+ controls. HDAC1 binding was significantly increased in AML
      blasts compared to CD34+ progenitor cells at 130 gene promoters whereas decreased
      binding was observed at 66 gene promoters. Distinct HDAC1 binding patterns
      occurred in AML subtypes with balanced translocations t(15;17), t(8;21) and
      inv(16). In addition, a more generalized signature was established, that revealed
      an AML specific pattern of HDAC1 distribution. Many of the HDAC1-binding altered
      promoters regulate genes involved in hematopoiesis, transcriptional regulation
      and signal transduction. HDAC1 binding patterns were associated with patients'
      event free survival. This is the first study to determine HDAC1 modification
      patterns in a large number of AML and ALL specimens. Our findings suggest that
      dyslocalization of HDAC1 is a common feature in AML. Importantly, HDAC1
      modifications possess prognostic power for patient survival. Our findings suggest
      that altered HDAC1 localization is an explanation for the observed benefit of
      HDAC inhibitors in AML therapy.

PMID- 21176960
TI  - Concomitant telomere shortening, acquisition of multiple chromosomal aberrations
      and in vitro resistance to apoptosis in a single case of progressive CLL.

PMID- 21176961
TI  - Hypoxia-inducible factor-1alpha protein expression is associated with poor
      survival in normal karyotype adult acute myeloid leukemia.
AB  - We examined the predictive impact of HIF-1alpha protein expression on clinical
      outcome of 84 normal karyotype acute myeloid leukemia (NK-AML) patients (median
      age 66.5 years) at our institute. Thirty percent of NK-AML cells expressed
      cytoplasmic HIF-1alpha. In univariate analysis, low HIF-1alpha (<= 5%, n = 66)
      was associated with improved event-free survival (p = 0.0453, HR = 0.22).
      Multivariate analysis incorporating age, complete remission, FLT3-ITD mutation,
      and marrow blast percentage demonstrated that HIF-1alpha was independently
      associated with poorer overall and event-free survival. HIF-1alpha expression
      correlated with VEGF-C but not VEGF-A, marrow angiogenesis, FLT3 ITD or NPM1
      mutations. These results support HIF-1alpha as an outcome marker for NK-AML.

PMID- 21176962
TI  - Can cyanobacterial biomass applied to soil affect survival and reproduction of
      springtail Folsomia candida?
AB  - Biomass of cyanobacterial water blooms including cyanobacterial toxins may enter
      soils, for example, when harvested water bloom is directly applied as an organic
      fertilizer or when water with massive cyanobacterial biomass is used for
      irrigation. In spite of this, no information is available about the potential
      effects on soil arthropods. The objective of this pilot study was to evaluate the
      effects of water bloom biomass sampled in five different fresh water lakes on the
      soil dwelling arthropod, springtail Folsomia candida (Collembola). These samples
      contained different dominant species of cyanobacteria and varied significantly in
      microcystin content (21-3662 MUg/g dw biomass). No adverse effects on survival or
      reproduction were observed for any tested sample at concentration up to 4 g dw
      biomass/kg dw soil. Despite the known hazardous properties of water blooms in
      aquatic ecosystems, our pilot results suggest that cyanobacterial biomass might
      have no significant impact on arthropods in soil. It remains a question, if this
      is due to low bioavailability of cyanobacterial toxins in soil.

PMID- 21176963
TI  - Evaluation of toxicity, genotoxicity and environmental risk of simulated textile
      and tannery wastewaters with a battery of biotests.
AB  - Textile and tannery wastewaters are complex mixtures of toxic pollutants and only
      a battery of ecotoxicity tests can assess their potential environmental impact
      and the actual effectiveness of alternative treatments. In this work the toxicity
      of four simulated textile and tannery wastewaters was evaluated by means of a
      battery of seven bioassays, using organisms that belong to different trophic
      levels. Moreover, since the outputs of the bioassay battery were quite difficult
      to compare, a novel synthetic index for environmental risk assessment was applied
      to the outputs of the test battery. All four simulated wastewaters were very
      toxic but they showed no mutagenic effect. The alga Pseudokirchneriella
      subcapitata was the most sensitive organism. In addition, the use of two
      mathematical models pointed out the interaction effect between dyes and salts,
      which resulted in a synergistic effect of wastewater toxicity.

PMID- 21176964
TI  - Genotoxicity and mutagenicity of water samples from the Monjolinho River (Brazil)
      after receiving untreated effluents.
AB  - Cytotoxicity, genotoxicity and mutagenicity assays, using the Allium cepa test
      system, were carried out in order to evaluate the effects of domestic and
      industrial effluents in the Monjolinho River in different seasons of the year. In
      the summer and intermediate seasons, chromosome aberration, micronuclei, cell
      death and inhibition of the mitotic index were observed in water samples
      collected at different sites. In the winter, either chromosome or cellular
      alterations were not observed. Through chemical analysis, we infer that the
      excessive metals such as Pb, Ni and Cu were mainly responsible for the effects
      observed in A. cepa cells. Limnologic analysis like electrical conductivity,
      dissolved oxygen and the presence of nitrogen and phosphated compounds showed
      that the river's contamination is due to organic matter discharge along its
      course. Moreover we note that this river had a higher self-depurative capacity at
      the end of its course, before its confluence with the Jacare-Guacu River.

PMID- 21176965
TI  - Spirometric tests to assess the prevalence of childhood asthma at Portuguese
      rural areas: influence of exposure to high ozone levels.
AB  - The study here reported aimed to: i) evaluate the prevalence of childhood asthma
      at a Portuguese rural area with high ozone concentrations through lung function
      tests, validating the previously estimated one assessed through questionnaires
      (similar to those of the ISAAC); ii) compare the achieved prevalence with the one
      reported at an unexposed area (with low ozone concentrations), aiming to evaluate
      the influence of exposure to high ozone levels; and iii) determine potential risk
      factors. Ninety-five of the original 478 children that completed the
      questionnaires, mentioned to have at least one of asthma symptoms (wheeze,
      dyspnea or cough) and were therefore evaluated by spirometry. FEV(1) was in
      average 89.7% for asthmatics and 102.8% for non-asthmatics. For the studied
      sample the risk was higher for girls with a tendency to be higher from 8 to 10
      years old. Lifetime prevalence of childhood asthma at the exposed area was 9.2%.
      Children living at the exposed area had 3 times higher risk of having asthma than
      those living at the unexposed area. Considering that ozone concentrations were
      the main difference between both areas, it can be suggested that ozone pollution
      increased asthma prevalence. Nevertheless, it should be remarked that further
      studies should be done to confirm these results.

PMID- 21176966
TI  - Analytical developments and preliminary assessment of human exposure to
      organophosphate flame retardants from indoor dust.
AB  - A new and efficient analytical method was developed and validated for the
      analysis of organophosphorus flame retardants (OPFRs) in indoor dust samples.
      This method involves an extraction step by ultrasonication and vortex, followed
      by extract clean-up with Florisil solid-phase extraction cartridges and analysis
      of the purified extracts by gas chromatography-mass spectrometry (GC-MS). Method
      recoveries ranged between 76 and 127%, except for volatile OPFRs, such as
      triethyl phosphate (TEP) and tri-(n-propyl) phosphate (TnPP), which were
      partially lost during evaporation steps. The between day precision on spiked dust
      samples was <14% for individual OPFRs, except for TEP, tri-iso-butyl phosphate
      (TiBP) and tri (2-butoxyethyl) phosphate (TBEP). Method limit of quantifications
      (LOQ) ranged between 0.02 MUg/g (TnPP and tris(1-chloro-2-propyl phosphate
      (TCPP)) and 0.50 MUg/g (TiBP). The method was further applied for the analysis of
      indoor dust samples taken from Flemish homes and stores. TiBP, TBEP and TCPP were
      most abundant OPFR with median concentrations of 2.99, 2.03 and 1.38 MUg/g in
      house dust and of 1.04, 3.61, and 2.94 MUg/g in store dust, respectively. The
      concentration of all OPFRs was at least 20 to 30 times higher compared to
      polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecanes (HBCDs).
      Estimated exposure to OPFRs from dust ingestion ranged for individual OPFRs
      between <1 and 50 ng/kg body weight for adults and toddlers, respectively. The
      estimated body burdens were 1000 to 100 times below reference dose (RfD) values,
      except for the scenario with high dust ingestion and high concentrations of TBEP
      in toddlers, where intake was only 5 times below RfD. Exposure of non-working and
      working adults to OPFRs appeared to be similar, but in specific work
      environments, exposure to some OPFRs (e.g. TDCPP) was increased by a factor >5.

PMID- 21176967
TI  - Tobacco-specific nitrosamines in water: an unexplored environmental health risk.

PMID- 21176968
TI  - A poster of pustules: representations of early twentieth century industrial
      anthrax in Britain.
AB  - In the decades around 1900, industrial anthrax attracted significant attention
      from medical practitioners, legislators and the general public in Britain.
      Attempts to reduce the incidence of the disease ranged from basic health measures
      - preventing workmen from eating inside factories and trialling the use of
      respirators - through to national legislation making disinfection of dangerous
      materials mandatory. Another effort involved the production of industrial warning
      posters (or cautionary notices) which were designed for use in the factory
      environment. In the case of anthrax, the context in which these notices appeared
      adds to our understanding of not only the disease itself, but also the relations
      between those producing such posters and those who encountered them in an
      industrial setting.

PMID- 21176969
TI  - Analysis of the cathelicidin 1 gene locus in Atlantic cod (Gadus morhua).
AB  - Cathelicidins are one of the major families of antimicrobial peptides produced as
      part of the innate immune responses. We have studied the gene locus of the
      Atlantic cod cathelicidin gene (gmCath1) by sequencing of a BAC clone. Results
      have revealed the genes upstream and downstream of gmCath1 in a sequence of >92.6
      kb and these include APG-9, obscurin, guanylate kinase and MMTA-2. There appears
      to be no pattern of synteny observed when the loci of cathelicidin genes in other
      species was analysed. Analysis of the promoter region of 1 kb upstream of the
      translation start codon led to the identification of numerous different putative
      transcription factor binding sites (TFBS) that are believed to be important for
      the control of immune gene expression. Further studies into the quantitative
      expression of gmCath1 found that it is constitutively expressed in the head
      kidney and spleen and significant increases in expression are observed at 24 h
      post injection with the immunostimulant ergosan. By inserting a 311 bp fragment
      of the gmCath1 promoter into a luciferase reporter vector we found that
      stimulation with Poly I:C results in significant up-regulation of gene
      expression. This report detailing the promoter region of a cathelicidin gene in
      teleost fish, and the varied putative TFBS identified, suggests that the gmCath1
      gene is highly likely to be induced in response to a wide range of different
      immune stimuli including bacteria and viruses.

PMID- 21176970
TI  - Going beyond students: an association between mixed-hand preference and
      schizotypy subscales in a general population.
AB  - Research on the sub-clinical condition of schizotypy suggests that it is
      associated with mixed handedness. To date, however, this research has focussed on
      undergraduate populations. If the association between schizotypy and mixed
      handedness is the result of an underlying neurological trait, it is important to
      demonstrate that the effect extends to the general population. With this in mind,
      699 participants were drawn from a wide community sample. Schizotypy was measured
      using the Psychosis Proneness Questionnaire and handedness was assessed using the
      Annett inventory. To avoid the sometimes arbitrary definitions of left-, right-
      and mixed-handed, regression analyses were used to explore the data. There was no
      evidence of a difference in schizotypy between individuals with a left- or right
      hand preference. People with a mixed-hand preference, however, had higher scores
      on PER-MAG (Perceptual Aberration and Magical Ideation) and HYP-IMP (Hypomania
      and Impulsive Non-Conformity) scales (positive traits). No effect was observed
      for the SAN (Social Anhedonia) and PAN (Physical Anhedonia) scales (negative
      traits). The nature of the association between schizotypy and handedness observed
      in the current study is similar to that reported for student populations. The
      possibility that the association is related to response biases or a biological
      mechanism is discussed.

PMID- 21176971
TI  - Cytokine and chemokine mRNA expression profiles in tracheobronchial lymph nodes
      from pigs singularly infected or coinfected with porcine circovirus type 2 (PCV2)
      and Mycoplasma hyopneumoniae (MHYO).
AB  - The objective of this study was to determine cytokine and chemokine mRNA
      expression profiles in tracheobronchial lymph nodes from pigs singularly infected
      with porcine circovirus type 2 (PCV2), Mycoplasma hyopneumoniae (MHYO), or
      coinfected with both. Twenty-eight pigs were randomly assigned to one of four
      groups: (1) negative controls (NEG), (2) inoculated with MHYO (IMHYO), (3)
      inoculated with MHYO and PCV2 (CoI), and (4) inoculated with PCV2 (IPCV2). MHYO
      infection significantly (P<0.05) stimulated innate cytokines, IL1B and IL8. PCV2
      infection significantly stimulated expression of IFNG, IL8, NOS2A and chemokines
      CCL2, CCL5, and CXCL10. IFNB, IL1B and IL12 were slightly increased with PCV2
      infection and IFNA and IL4 were significantly downregulated. Compared to NEG
      pigs, coinfection resulted in a significant increase in expression of IFNG, IL1B,
      IL8, CCL5, CXCL10, and weak stimulation of IFNB, IL6 and IL10; IL13 and IFNA were
      significantly downregulated. Overall MHYO potentiated PCV2 infection by
      increasing IFNG and IL10 mRNA expression levels. The increase of IFNG and
      chemokines and decrease of IFNA in IPCV2 and CoI pigs were correlated with
      increased severity of lymphoid lesions and the presence of PCV2 antigen. In
      summary, this work provided evidence that the increased severity of lesions in
      PCV2 and MHYO coinfected pigs was associated mainly with the presence of PCV2
      antigen and alterations of cytokine mRNA expression profiles.

PMID- 21176972
TI  - Additive effects of orexin B and vasoactive intestinal polypeptide on LL-37
      mediated antimicrobial activities.
AB  - The present study examined the bactericidal effects of orexin B (ORXB) and
      vasoactive intestinal peptide (VIP) alone or combined with cationic antimicrobial
      peptides, such as LL-37, on Escherichia coli, Pseudomonas aeruginosa,
      Streptococcus mutans and Staphylococcus aureus. The bactericidal effect of ORXB
      or VIP alone was detected in low NaCl concentration, but attenuated in
      physiological NaCl concentration (150 mM). However, such attenuated bactericidal
      activities of ORXB and VIP in 150 mM NaCl were regained by adding LL-37.
      Therefore, our results indicate that VIP and ORXB appear to mediate bactericidal
      effects in concert with LL-37 in the physiological context of mucosal tissue.

PMID- 21176973
TI  - Peptide reactivity between multiple sclerosis (MS) CSF IgG and recombinant
      antibodies generated from clonally expanded plasma cells in MS CSF.
AB  - We employed 19 recombinant antibodies (rAbs) generated from clonally expanded
      plasma cells, and native IgG from cerebrospinal fluid (CSF) of three multiple
      sclerosis (MS) patients for panning with phage displayed random peptide
      libraries. Specific peptide epitopes/mimotopes were identified and characterized.
      Importantly, peptide-antibody interactions were shared by rAbs and native IgG
      from the same patient. Three peptides strongly interacted with at least one other
      MS CSF, but not to inflammatory CNS controls. Database searches revealed several
      protein candidates including stress proteins, cell surface proteins, and neuronal
      proteins. Peptides derived from the candidate proteins were recognized by rAbs.
      Identification of peptide epitopes/mimotopes in MS may provide clues regarding
      disease-relevant antigens.

PMID- 21176974
TI  - The genetic basis of auditory neuropathy spectrum disorder (ANSD).
AB  - OBJECTIVE: Auditory neuropathy is a hearing disorder where outer hair cell
      function within the cochlea is normal, but inner hair cell and/or the auditory
      nerve function is disrupted. It is a heterogeneous disorder which can have either
      congenital or acquired causes. Furthermore, the aetiology of auditory neuropathy
      is vast, which may include prematurity, hyperbilirubinaemia, anoxia, hypoxia,
      congenital brain anomalies, ototoxic drug exposure, and genetic factors. It is
      estimated that approximately 40% of cases have an underlying genetic basis, which
      can be inherited in both syndromic and non syndromic conditions. This review
      paper provides an overview of the genetic conditions associated with auditory
      neuropathy spectrum disorders (ANSDs) and highlights some of the defective genes
      that have been found to be linked to the pathological auditory changes. METHOD:
      Literature search was conducted using a number of resources including textbooks,
      professional journals and the relevant websites. RESULTS: The largest proportion
      of auditory neuropathy spectrum disorders (ANSDs) is due to genetic factors which
      can be syndromic, non-syndromic or mitochondrial related. The inheritance pattern
      can include all the four main types of inheritances such as autosomal dominant,
      autosomal recessive, X-linked and mitochondrial. CONCLUSION: This paper has
      provided an overview of mutation with some of the genes and/or loci discovered to
      be the cause for auditory neuropathy spectrum disorders (ANSDs). It has been
      noted that different gene mutations may trigger different pathological changes in
      patients with this disorder. These discoveries have provided us with vital
      information as to the sites of pathology in auditory neuropathy spectrum
      disorders (ANSDs), and the results highlight the heterogeneity of the disorder.

PMID- 21176975
TI  - Learning to move machines with the mind.
AB  - Brain-computer interfaces (BCIs) extract signals from neural activity to control
      remote devices ranging from computer cursors to limb-like robots. They show great
      potential to help patients with severe motor deficits perform everyday tasks
      without the constant assistance of caregivers. Understanding the neural
      mechanisms by which subjects use BCI systems could lead to improved designs and
      provide unique insights into normal motor control and skill acquisition. However,
      reports vary considerably about how much training is required to use a BCI
      system, the degree to which performance improves with practice and the underlying
      neural mechanisms. This review examines these diverse findings, their potential
      relationship with motor learning during overt arm movements, and other
      outstanding questions concerning the volitional control of BCI systems.

PMID- 21176976
TI  - Disability in elderly patients with chronic neurological illness: stroke,
      multiple sclerosis and epilepsy.
AB  - The aim of the study was to evaluate disability in patients with elderly stroke,
      multiple sclerosis (MS) and epilepsy, and to analyze its relationship with
      demographic characteristics. We conducted a cross-sectional study involving 113
      patients with neurological diseases. The data were collected with a Personal
      Information Form, the Rivermead Mobility Index (RMI), and the Brief Disability
      Questionnaire (BDQ) were used. The data were evaluated using percentage, variance
      analysis, the Kruskal-Wallis test and the Pearson correlation analysis. The study
      results demonstrate that among three disorders, the severity of disability
      increased in patients with stroke, epilepsy and MS, respectively. It was also
      found that in patients with stroke, MS and epilepsy experiencing disability in
      mobility, 32.7% had experienced moderate physical-social disability, and 63.3%
      had experienced severe physical-social disability, and that there was a
      significantly high relationship between mobility disability and physical-social
      disability. The severity of disability was found to be higher for older age, low
      level education, self-employed and widows. Especially in stroke patients,
      disability is a common problem in patients with epilepsy and MS. Detecting the
      level of disability is very important for decreasing the limitation in elderly
      patients with neurological illness.

PMID- 21176977
TI  - Hypertension and angiogenesis in the aging kidney: a review.
AB  - With advanced aging, main components of the kidney are altered, including blood
      vessels, glomeruli and tubulointerstitium. Disruption in these 3 elements is
      interconnected and associated with several modifications, such as loss of kidney
      mass and systemic, metabolic and immunologic diseases. In this review we focus on
      renal blood vessels, the key role of hypertension and angiogenesis in the elderly
      kidney, the hemodynamic and molecular mechanisms underlying this aging process
      and the main factors involved. So far, the present data suggests a strong
      association between renal disease and hypertension and the impairment of
      regulatory mechanisms, such as angiogenesis in the aging kidney. The endothelium
      is a key player in vascular control and appears to be also disrupted in many
      compensatory functions (i.e., vasodilation). Perspectives for the management of
      the dysfunctional aging kidney are also addressed.

PMID- 21176978
TI  - Criminal activities of the elderly in Turkey during the years 2000-2005.
AB  - The aging of the population is one of the most important demographic events of
      the 21st century. The aim of this study is to define the basic variables related
      with criminal behavior among the elderly for cases over 60 years. A retrospective
      assessment of the criminal data (255 cases) consists of the period between 2000
      and 2005 of the Council of Forensic Medicine, Turkish Ministry of Justice. Of the
      cases whose average age is 68.2+/-6.9, 25 of the 56 cases were diagnosed as ill.
      Out of 225 elderly who had committed a criminal act 56 of them had a medical
      antecedent which is a psychiatric diagnosis. Whether or not they had a medical
      antecedent the Board made 90 psychiatric diagnosis. This comprised of 25 out of
      the 56 who also had a medical antecedent and 65 out of the 199 who did not have a
      medical antecedent. Delusional disorder (43.3%) and schizophrenia (25.6%) are the
      most frequent diagnoses. Specializing and developing standards for determining
      the criminal responsibility of the elderly is required.

PMID- 21176979
TI  - Dobutamine-induced changes of left atrial two-dimensional deformation predict
      clinical and neurohumoral improvement after levosimendan treatment in patients
      with acutely decompensated chronic heart failure.
AB  - BACKGROUND: We investigated whether dobutamine-induced changes of the left atrial
      (LA) two-dimensional speckle tracking parameters are related to clinical and
      neurohumoral improvement after levosimendan treatment in patients with acutely
      decompensate chronic heart failure (ADCHF). METHODS: Forty-six patients with
      ADCHF and LV ejection fraction <35%, were studied using dobutamine stress
      echocardiography before a 24-hour infusion of levosimendan. In a multivariable
      model, we included: dobutamine-induced LV contractile reserve, change (%) of LA
      volume, LV longitudinal strain rate and LA speckle tracking parameters to assess
      the improvement of NYHA class, 6-min walk distance and brain natriuretic peptide
      (BNP). RESULTS: The change (%) of LA-contractile strain and LV longitudinal stain
      rate were independent determinants of improvement of NYHA class, and BNP and
      increase in the 6-min walk test distance (b=-0.59, b=-0.65, b=0.41, and b=-0.44,
      b=-0.40, b=0.60, respectively, p<0.05). The addition of LA-contractile strain
      change in the multivariable analysis including LV longitudinal stain rate change
      increased the value of the model from r(2)=0.46 to 0.58 for NYHA improvement and
      from r(2)=0.44 to 0.70, for the BNP reduction and from r(2)=0.49 to 0.60, for
      increase in the 6-min walk test distance (p<0.05). The change (%) of LA-reservoir
      strain was univariate determinant for increase in the 6-min walk test distance
      (b=-0.37, p=0.02) and increased the value of the multivariate model from
      r(2)=0.46 to 0.58, p=0.02. CONCLUSION: In patients with ADCHF, left atrial two
      dimensional speckle tracking parameters in addition to LV longitudinal strain
      rate may detect those patients who are prone to improve after levosimendan
      treatment.

PMID- 21176980
TI  - A systematic review of the effectiveness of oral health promotion activities
      among patients with cardiovascular disease.
AB  - AIMS: This study aimed to review the effectiveness of oral health promotion
      activities conducted among patients with cardiovascular disease. METHODS AND
      RESULTS: Three electronic databases were searched for effective papers using
      standardized search methods, and key findings of effective studies were
      summarized. The initial search yielded 3101 papers but only 8 studies met the
      criteria for this review: 3 were randomized controlled studies, 3 were pre-/post
      group interventions, 1 was a randomized split-mouth study, and 1 was a quasi
      experimental study. Studies retrieved concerned oral health promotion activities
      in patients with coronary heart disease, hypertension, heart transplantation, and
      stroke. Interventions comprised periodontal treatment performed by dental
      personnel, and oral hygiene interventions provided by nursing home care
      assistants. Outcomes included improvements in periodontal health, and
      modifications of systemic inflammatory markers. No studies, however, evaluated
      the effects of oral health promotion interventions on oral microflora.
      CONCLUSION: There are limited studies on the efficacy of oral health promotion
      activities in patients with cardiovascular disease, particularly stroke patients.
      Oral health promotion activities appear to produce improvements in periodontal
      health, and also result in changes to systemic markers of inflammation and
      endothelial function (at least) in the short term. Whether these effects can
      ultimately lower the risk of secondary cardiovascular events has not yet been
      determined.

PMID- 21176981
TI  - Factors associated with surgery for active endocarditis in congenital heart
      disease.
AB  - BACKGROUND: Despite the recent progress of cardiac surgery, the indications for
      surgical intervention during the active phase of infective endocarditis have not
      yet been established in patients with congenital heart diseases due to the
      limited number of such patients. The present study aims to determine the surgical
      indications for active infective endocarditis in congenital heart diseases.
      METHODS: A retrospective observational cohort multi-center study on infective
      endocarditis with congenital heart diseases was conducted from January 1997 to
      December 2001 in Japan and 239 patients were registered. Sixty-one (26%) of the
      239 patients had undergone surgical therapy for active infective endocarditis,
      which was defined as cardiac surgery during administration of intravenous
      antibiotics. RESULTS: There were 7 deaths (11%). A univariate regression analysis
      revealed that the factors significantly associated with the need for surgical
      intervention for active IE were the lack of diagnosis of cardiac disorders before
      the onset of infective endocarditis, aortic valve infective endocarditis,
      perivalvular abscess, presence of heart failure, and change of antibiotics. A
      stepwise logistic regression analysis revealed that the presence of a
      perivalvular abscess, heart failure and a change in the antibiotics were
      independent determinant factors for the need for surgical treatment of active
      infective endocarditis in patients with congenital heart diseases. CONCLUSIONS:
      Surgery should therefore be considered even during the active phase in patients
      with congenital heart diseases and infective endocarditis, when they develop
      associated with heart failure, a perivalvular abscess, or the need for a change
      in antibiotics.

PMID- 21176982
TI  - Bayesian analysis of animal movements related to factors at herd and between herd
      levels: Implications for disease spread modeling.
AB  - A method to assess the influence of between herd distances, production types and
      herd sizes on patterns of between herd contacts is presented. It was applied on
      pig movement data from a central database of the Swedish Board of Agriculture. To
      determine the influence of these factors on the contact between holdings we used
      a Bayesian model and Markov chain Monte Carlo (MCMC) methods to estimate the
      posterior distribution of model parameters. The analysis showed that the contact
      pattern via animal movements is highly heterogeneous and influenced by all three
      factors, production type, herd size, and distance between holdings. Most
      production types showed a positive relationship between maximum capacity and the
      probability of both incoming and outgoing movements. In agreement with previous
      studies, holdings also differed in both the number of contacts as well as with
      what holding types contact occurred with. Also, the scale and shape of distance
      dependence in contact probability was shown to differ depending on the production
      types of holdings.To demonstrate how the methodology may be used for risk
      assessment, disease transmissions via animal movements were simulated with the
      model used for analysis of contacts, and parameterized by the analyzed posterior
      distribution. A Generalized Linear Model showed that herds with production types
      Sow pool center, Multiplying herd and Nucleus herd have higher risk of generating
      a large number of new infections. Multiplying herds are also expected to generate
      many long distance transmissions, while transmissions generated by Sow pool
      centers are confined to more local areas. We argue that the methodology presented
      may be a useful tool for improvement of risk assessment based on data found in
      central databases.

PMID- 21176983
TI  - Helical tomotherapy and intensity modulated proton therapy in the treatment of
      early stage prostate cancer: a treatment planning comparison.
AB  - PURPOSE: To compare helical tomotherapy (HT) and intensity modulated proton
      therapy (IMPT) on early stage prostate cancer treatments delivered with
      simultaneous integrated boost (SIB) in moderate hypofractionation.
      MATERIAL/METHODS: Eight patients treated with HT were replanned with two-field
      IMPT (2fIMPT) and five-field IMPT (5fIMPT), using a small pencil beam size (3 mm
      sigma). The prescribed dose was 74.3 Gy in 28 fractions on PTV1 (prostate) and
      PTV2 (proximal seminal vesicles), 65.5 Gy on PTV3 (distal seminal vesicles) and
      on the overlap between rectum and PTVs. RESULTS: IMPT and HT achieved similar
      target coverage and dose homogeneity, with 5fIMPT providing the best results. The
      conformity indexes of IMPT were significantly lower for PTV1+2 and PTV3. Above 65
      Gy, HT and IMPT were equivalent in the rectum, while IMPT spared the bladder and
      the penile bulb from 0 to 70 Gy. From 0 up to 60 Gy, IMPT dosimetric values were
      (much) lower for all OARs except the femur heads, where HT was better than 2fIMPT
      in the 25-35 Gy dose range. OARs mean doses were typically reduced by 30-50% by
      IMPT. NTCPs for the rectum were within 1% between the two techniques, except when
      the endpoint was stool frequency, where IMPT showed a small (though statistically
      significant) benefit. CONCLUSIONS: HT and IMPT produce similar dose distributions
      in the target volume. The current knowledge on dose-effect relations does not
      allow to quantify the clinical impact of the large sparing of IMPT at medium-to
      low doses.

PMID- 21176984
TI  - Feasibility of CBCT-based target and normal structure delineation in prostate
      cancer radiotherapy: multi-observer and image multi-modality study.
AB  - BACKGROUND AND PURPOSE: In-room cone-beam CT (CBCT) imaging and adaptive
      treatment strategies are promising methods to decrease target volumes and to
      spare organs at risk. The aim of this work was to analyze the inter-observer
      contouring uncertainties of target volumes and organs at risks (oars) in
      localized prostate cancer radiotherapy using CBCT images. Furthermore, CBCT
      contouring was benchmarked against other image modalities (CT, MR) and the
      influence of subjective image quality perception on inter-observer variability
      was assessed. METHODS AND MATERIALS: Eight prostate cancer patients were
      selected. Seven radiation oncologists contoured target volumes and oars on CT,
      MRI and CBCT. Volumes, coefficient of variation (COV), conformity index (cigen),
      and coordinates of center-of-mass (COM) were calculated for each patient and
      image modality. Reliability analysis was performed for the support of the
      reported findings. Subjective perception of image quality was assessed via a ten
      scored visual analog scale (VAS). RESULTS: The median volume for prostate was
      larger on CT compared to MRI and CBCT images. The inter-observer variation for
      prostate was larger on CBCT (CIgen=0.57+/-0.09, 0.61 reliability) compared to CT
      (CIgen=0.72+/-0.07, 0.83 reliability) and MRI (CIgen=0.66+/-0.12, 0.87
      reliability). On all image modalities values of the intra-observer reliability
      coefficient (0.97 for CT, 0.99 for MR and 0.94 for CBCT) indicated high
      reproducibility of results. For all patients the root mean square (RMS) of the
      inter-observer standard deviation (sigma) of the COM was largest on CBCT with
      sigma(x)=0.4 mm, sigma(y)=1.1 mm, and sigma(z)=1.7 mm. The concordance in
      delineating OARs was much stronger than for target volumes, with average
      CIgen>0.70 for rectum and CIgen>0.80 for bladder. Positive correlations between
      CIgen and VAS score of the image quality were observed for the prostate, seminal
      vesicles and rectum. CONCLUSIONS: Inter-observer variability for target volume
      delineation in prostate cancer is larger for CBCT-based contouring compared to CT
      and MRI. This factor of influence needs to be considered when defining safety
      margins for CBCT-based Adaptive Radiotherapy (ART).

PMID- 21176985
TI  - A phase I trial combining oral cisplatin (CP Ethypharm) with radiotherapy in
      patients with locally advanced head and neck squamous cell carcinoma.
AB  - PURPOSE: To determine the maximum tolerated dose (MTD) of oral cisplatin (CP
      Ethypharm(r)) in combination with radiotherapy in head and neck squamous cell
      carcinoma (HNSCC) and the recommended dose for phase II trials. PATIENTS AND
      METHODS: Phase I, multicenter, open-labelled, non-comparative and dose escalating
      trial. CP Ethypharm(r) was administered on five consecutive days every other week
      for 7 weeks (4 treatment cycles) in combination with radiotherapy. Eighteen
      patients with locally advanced HNSCC were allocated to four cisplatin dose
      levels: 10 mg/m(2)/day: 4 patients; 15 mg/m(2)/day: 4, 20 mg/m(2)/day: 5 and 25
      mg/m(2)/day: 5. The inclusion of patients was dictated by occurrence of dose
      limiting toxicities (DLTs) at each dosing level. RESULTS: The most frequently
      experienced AEs were gastrointestinal (GI) disorders. Five DLTs were observed,
      including three at 25 mg/m(2) level (two grade 2 renal toxicities, one grade 3 GI
      and renal toxicities), one at 20 mg/m(2) level (grade 3 GI disorders), one at 10
      mg/m(2) level (grade 4 mucositis). PK analysis showed no significant difference
      of C(max) values between day 1 and day 5 of treatment at each dose level (total &
      ultrafilterable platinum). CONCLUSION: Due to 3 DLTs experienced at 25
      mg/m(2)/day, MTD was reached and the recommended dose for phase II studies was
      determined as 20 mg/m(2)/day.

PMID- 21176986
TI  - Development and external validation of a predictive model for pathological
      complete response of rectal cancer patients including sequential PET-CT imaging.
AB  - PURPOSE: To develop and validate an accurate predictive model and a nomogram for
      pathologic complete response (pCR) after chemoradiotherapy (CRT) for rectal
      cancer based on clinical and sequential PET-CT data. Accurate prediction could
      enable more individualised surgical approaches, including less extensive
      resection or even a wait-and-see policy. METHODS AND MATERIALS: Population based
      databases from 953 patients were collected from four different institutes and
      divided into three groups: clinical factors (training: 677 patients, validation:
      85 patients), pre-CRT PET-CT (training: 114 patients, validation: 37 patients)
      and post-CRT PET-CT (training: 107 patients, validation: 55 patients). A pCR was
      defined as ypT0N0 reported by pathology after surgery. The data were analysed
      using a linear multivariate classification model (support vector machine), and
      the model's performance was evaluated using the area under the curve (AUC) of the
      receiver operating characteristic (ROC) curve. RESULTS: The occurrence rate of
      pCR in the datasets was between 15% and 31%. The model based on clinical
      variables (AUC(train)=0.61+/-0.03, AUC(validation)=0.69+/-0.08) resulted in the
      following predictors: cT- and cN-stage and tumour length. Addition of pre-CRT PET
      data did not result in a significantly higher performance (AUC(train)=0.68+/
      0.08, AUC(validation)=0.68+/-0.10) and revealed maximal radioactive isotope
      uptake (SUV(max)) and tumour location as extra predictors. The best model
      achieved was based on the addition of post-CRT PET-data (AUC(train)=0.83+/-0.05,
      AUC(validation)=0.86+/-0.05) and included the following predictors: tumour
      length, post-CRT SUV(max) and relative change of SUV(max). This model performed
      significantly better than the clinical model (p(train)<0.001,
      p(validation)=0.056). CONCLUSIONS: The model and the nomogram developed based on
      clinical and sequential PET-CT data can accurately predict pCR, and can be used
      as a decision support tool for surgery after prospective validation.

PMID- 21176987
TI  - Monoterpene alcohols release and bioconversion by Saccharomyces species and
      hybrids.
AB  - Terpene profile of Muscat wines fermented by Saccharomyces species and hybrid
      yeasts was investigated. The amount of geraniol decreased in most wines with
      respect to the initial must except for Saccharomyces bayanus wines. On the other
      hand, alpha-terpineol amount was higher in wines fermented by Saccharomyces
      cerevisiae and hybrid yeasts. The amount of linalool was similar in all wines and
      comparable to the amount in the initial must. Lower levels of beta-D-glucosidase
      activity were found in the hybrid yeasts with respect to S. cerevisiae. Moreover,
      no relationship between beta-D-glucosidase activity and terpenes profile in
      Muscat wines fermented with Saccharomyces species and hybrids was found. Growth
      of yeasts on minimum medium supplemented with geraniol showed bioconversion of
      geraniol into linalool and alpha-terpineol. Percentages of geraniol uptake and
      bioconversion were different between Saccharomyces species and hybrids. Strains
      within S. bayanus, Saccharomyces kudriavzevii and hybrids showed higher geraniol
      uptake than S. cerevisiae, whereas the percentage of produced linalool and alpha
      terpineol was higher in S. cerevisiae and hybrid yeasts than in S. bayanus and S.
      kudriavzevii. The relationship between geraniol uptake and adaptation of
      Saccharomyces species to grow at low temperature is discussed.

PMID- 21176988
TI  - The inhibitory effect of natural microflora of food on growth of Listeria
      monocytogenes in enrichment broths.
AB  - The aims of this study were to (i) compare the inhibitory effects of the natural
      microflora of different foods on the growth of Listeria monocytogenes during
      enrichment in selective and non-selective broths; (ii) to isolate and identify
      components of the microflora of the most inhibitory food; and (iii) to determine
      which of these components was most inhibitory to growth of L. monocytogenes in co
      culture studies. Growth of an antibiotic-resistant marker strain of L.
      monocytogenes was examined during enrichment of a range of different foods in
      Tryptone Soya Broth (TSB), Half Fraser Broth (HFB) and Oxoid Novel Enrichment
      (ONE) Broth. Inhibition of L. monocytogenes was greatest in the presence of
      minced beef, salami and soft cheese and least with prepared fresh salad and
      chicken pate. For any particular food the numbers of L. monocytogenes present
      after 24h enrichment in different broths increased in the order: TSB, HFB and ONE
      Broth. Numbers of L. monocytogenes recovered after enrichment in TSB were
      inversely related to the initial aerobic plate count (APC) in the food but with
      only a moderate coefficient of determination (R(2)) of 0.51 implying that
      microbial numbers and the composition of the microflora both influenced the
      degree of inhibition of L. monocytogenes. In HFB and ONE Broth the relationship
      between APC and final L. monocytogenes counts was weaker. The microflora of TSB
      after 24h enrichment of minced beef consisted of lactic acid bacteria,
      Brochothrix thermosphacta, Pseudomonas spp., Enterobacteriaceae, and enterococci.
      In co-culture studies of L. monocytogenes with different components of the
      microflora in TSB, the lactic acid bacteria were the most inhibitory followed by
      the Enterobacteriaceae. The least inhibitory organisms were Pseudomonas sp.,
      enterococci and B. thermosphacta. In HFB and ONE Broth the growth of Gram
      negative organisms was inhibited but lactic acid bacteria still reached high
      numbers after 24h. A more detailed study of the growth of low numbers of L.
      monocytogenes during enrichment of minced beef in TSB revealed that growth of L.
      monocytogenes ceased at a cell concentration of about 10(2)cfu/ml when lactic
      acid bacteria entered stationary phase. However in ONE Broth growth of lactic
      acid bacteria was slower than in TSB with a longer lag time allowing L.
      monocytogenes to achieve much higher numbers before lactic acid bacteria reached
      stationary phase. This work has identified the relative inhibitory effects of
      different components of a natural food microflora and shown that the ability of
      low numbers of L. monocytogenes to achieve high cell concentrations is highly
      dependent on the extent to which enrichment media are able to inhibit or delay
      growth of the more effective competitors.

PMID- 21176989
TI  - Modelling the fate of Listeria monocytogenes during manufacture and ripening of
      smeared cheese made with pasteurised or raw milk.
AB  - The dynamics of the physicochemical characteristics of foods help to determine
      the fate of pathogens throughout processing. The aim of this study was to assess
      the behaviour of Listeria monocytogenes during cheesesmaking and ripening and to
      model the growth observed under the dynamic conditions of the cheese. A
      laboratory scale cheese was made in 4 independent replicates from pasteurised or
      raw cow's milk, artificially contaminated with L. monocytogenes. No growth of L.
      monocytogenes occurred during raw milk cheese-making, whereas growth did occur in
      pasteurised milk. During ripening, growth occurred in raw milk cheese, but
      inactivation occurred in pasteurised milk cheese. The behaviour observed for L.
      monocytogenes was modelled using a logistic primary model coupled with a
      secondary cardinal model, taking into account the effect of physicochemical
      conditions (temperature, pH, water activity and lactate). A novel statistical
      approach was proposed to assess the optimal growth rate of a microorganism from
      experiments performed in dynamic conditions. This complex model had an acceptable
      quality of fit on the experimental data. The estimated optimum growth rates can
      be used to predict the fate of L. monocytogenes during cheese manufacture in raw
      or pasteurized milk in different physicochemical conditions. The data obtained
      contributes to a better understanding of the potential risk that L. monocytogenes
      presents to cheese producers (growth on the product, if it is contaminated) and
      consumers (the presence of high numbers) and constitutes a very useful set of
      data for the completion of chain-based modelling studies.

PMID- 21176990
TI  - Multilocus sequence typing of Propionibacterium freudenreichii.
AB  - Propionibacterium freudenreichii is used as a ripening culture in Swiss cheese
      manufacture. This study investigates the molecular diversity and the population
      structure of this bacterium via multilocus sequence typing (MLST). Internal
      fragments of seven genes sequenced for 113 strains of different subspecies and
      origins allowed the resolution of 46 sequence types (STs) with occurrence
      frequencies ranging from 1 to 11. The core genome of the species harbours a low
      level of nucleotide polymorphism. In our data, single nucleotide polymorphisms
      account for only 2.28% of the concatenated sequences, and the average
      polymorphism rate in pairwise comparisons is 0.46%. The analyses reveal
      quantitatively comparable contributions of recombination and mutation in
      nucleotide changes at core genome loci along cell lineages. Remarkably, the STs
      exhibit little if any dairy biotope specialization. Phenotypic characterisation
      of the strains, based on their aptitude to use lactose and nitrate, shows that
      the two previously identified subspecies (freudenreichii and shermani) do not
      reflect the ancestral relationships in the P. freudenreichii population. The
      considerable phenotypic heterogeneity, found even at the ST level, suggests
      instead a history of recurrent switches between phenotypes.

PMID- 21176991
TI  - Viral Interleukin-6: Structure, pathophysiology and strategies of neutralization.
AB  - Viral Interleukin-6 (vIL-6) is encoded by Human herpes virus 8 (HHV8), also known
      as Kaposi's sarcoma (KS)-associated herpes virus (KSHV). HHV8 infection is found
      in patients with KS, primary effusion lymphoma (PEL) and plasma cell-type of
      multicentric Castleman's disease (MCD), with a high incidence observed in HIV
      infected individuals. vIL-6 shares about 25% identity with its human counterpart.
      Human IL-6 (hIL-6) binds to the human IL-6 receptor (hIL-6R) and the hIL-6/hIL-6R
      complex associates with the signaling receptor subunit gp130. Upon dimerization
      of gp130 intracellular signaling is initiated. All cells in the body express
      gp130 but only some cell types express the hIL-6R. Human IL-6 does not stimulate
      cells, which do not express hIL-6R. However, a naturally occurring soluble form
      of the hIL-6R (shIL-6R) can bind hIL-6 and the complex of hIL-6/shIL-6R can
      stimulate cells, which only express gp130 but no hIL-6R. This process, which has
      been named trans-signaling, leads to a dramatic increase in the spectrum of hIL-6
      target cells during inflammation and cancer. vIL-6, in contrast to hIL-6, can
      directly bind to and activate gp130 without the need of the hIL-6R. Therefore, at
      least in theory, vIL-6 can stimulate every cell in the human body. This review
      highlights the properties of vIL-6 regarding structural features, implications
      for pathophysiology, and strategies of neutralization. Furthermore, mechanisms of
      activation of gp130 by hIL-6, vIL-6, and by forced dimerization will be
      discussed.

PMID- 21176992
TI  - Distinct roles of JNK-1 and ERK-2 isoforms in permeability barrier repair and
      wound healing.
AB  - c-Jun N-terminal kinases (JNKs, also called stress activated protein kinases) and
      the extra-cellular signal responsive kinases (ERKs) exert different functions in
      mitogenesis, maturation and differentiation of immune and epithelial cells. We
      investigated specific functions of individual JNK and ERK isoforms in skin
      permeability barrier repair and in wound healing. JNK1, but not JNK2 or JNK3,
      deficient mice revealed a delay in the permeability barrier repair after
      superficial injury to the skin (tape-stripping) as well as a delay in the healing
      of full skin thickness wounds. Skin barrier injury induced an increase in
      epidermal JNK1 enzyme activity in mouse skin in vivo, and JNK1 activity
      correlated with the degree of differentiation in organotypic keratinocyte
      cultures. Skin injury activated epidermal ERK2 enzyme activity with biphasic
      maxima after 30 min and 3h, and the activity was independent from the
      differentiation state in keratinocyte culture. In summary, superficial and deep
      wound healing depends on the differential activity of MAP kinases such as JNK1 in
      epidermal differentiation and ERK2 in proliferation.

PMID- 21176993
TI  - [Conjunctival epidermoid carcinoma revealed by a chronic limbic corneal
      ulceration].
AB  - PURPOSE: Conjunctival epidermoid carcinoma (CEC) is a rare tumor affecting mainly
      the perilimbal region of the bulbar conjunctiva. We report an atypical
      presentation of a CEC mimicking a Mooren pseudo-ulcer. CASE REPORT: A 78-year-old
      man presented a limbic corneal ulcer of the left eye that had appeared a few
      months before. Ophthalmologic examination showed a thinning limbic corneal
      ulceration, associated with substantial conjunctival thickening. The diagnosis of
      Mooren pseudo-ulcer was first suspected. Etiological investigations were
      negative. The worsening of the corneal ulcer led us to perform surgical excision
      on the conjunctiva around the ulcer. Histologic examination concluded in an
      invasive conjunctival carcinoma. Adjuvant radiotherapy was required because of
      incomplete surgical excision and chorion tumoral invasion.

PMID- 21176994
TI  - [Toxic anterior segment syndrome].
AB  - Toxic anterior segment syndrome (TASS) is a general term used to describe acute,
      sterile postoperative inflammation due to a non-infectious substance that
      accidentally enters the anterior segment at the time of surgery and mimics
      infectious endophthalmitis. TASS most commonly occurs acutely following anterior
      segment surgery, typically 12-72h after cataract extraction. Anterior segment
      inflammation is usually quite severe with hypopyon. Endothelial cell damage is
      common, resulting in diffuse corneal edema. No bacterium is isolated from ocular
      samples. The causes of TASS are numerous and difficult to isolate. Any device or
      substance used during the surgery or in the immediate postoperative period may be
      implicated. The major known causes include: preservatives in ophthalmic
      solutions, denatured ophthalmic viscosurgical devices, bacterial endotoxin, and
      intraocular lens-induced inflammation. Clinical features of infectious and non
      infectious inflammation are initially indistinguishable and TASS is usually
      diagnosed and treated as acute endophthalmitis. It usually improves with local
      steroid treatment but may result in chronic elevation of intraocular pressure or
      irreversible corneal edema due to permanent damage of trabecular meshwork or
      endothelial cells.

PMID- 21176995
TI  - Evidence-based emergency medicine. Is MRI more accurate than CT in patients with
      suspected acute stroke?

PMID- 21176996
TI  - Clinical significance of nosocomial acquisition in urinary tract-related
      bacteremia caused by gram-negative bacilli.
AB  - BACKGROUND: Although hospital-acquired infections presumably may have a poorer
      prognosis than community-onset infections because of unanticipated antimicrobial
      resistance, little data are available on the clinical and microbiological
      characteristics of hospital-acquired versus community-onset urinary tract-related
      bacteremia cases. METHODS: Data were collected from a nationwide database of
      surveillance for bacteremia. Data from patients with hospital-acquired urinary
      tract-related bacteremia were compared with those with community-onset
      bacteremia. RESULTS: Of 398 patients with urinary tract-related bacteremia, 71
      (17.8%) had hospital-acquired infection, and the remaining 327 (82.2%) had
      community-onset infection. Although Escherichia coli was the most common isolate
      identified, pathogens other than E coli were more frequently isolated in hospital
      acquired infections than in community-onset infections (46.5% vs 19.3%). Among E
      coli isolates causing hospital-acquired infections, 26.3% (10 of 38) were
      resistant to extended-spectrum cephalosporins (ESCs), whereas among E coli
      isolates causing community-onset infections, only 6.1% (16 of 264) were ESC
      resistant. Hospital-acquired infection had a significantly higher mortality rate
      than community-onset infection (21.1% [15 of 71] vs 8.3% [27 of 327]; P = .004).
      Multivariate analysis identified nosocomial acquisition as a significant
      independent risk factor for mortality, along with severe sepsis, underlying solid
      tumor, ESC resistance, and high Pitt bacteremia score (all P < .05). CONCLUSION:
      Hospital-acquired urinary tract-related bacteremia has a poorer prognosis than
      community-onset bacteremia. The ESC-resistant nature of gram-negative bacilli,
      which may be more common in nosocomial isolates than in community isolates,
      adversely affects the outcome of urinary tract-related bacteremia.

PMID- 21176997
TI  - Striatal dopamine transporter binding correlates with serum BDNF levels in
      patients with striatal dopaminergic neurodegeneration.
AB  - Compelling evidence has shown, that neurotrophins responsible for the regulation
      of neuronal growth, survival, and differentiation are involved in
      neurodegenerative diseases. Whereas lower serum levels of brain derived
      neurotrophic factor (BDNF) have been observed in patients with Parkinson's
      disease, no studies have directly related the degree of striatal
      neurodegeneration of dopaminergic neurons (DA) with serum BDNF levels. In this
      study we examined the relationship between striatal neurodegeneration as
      determined with (123)I-PE2I-single photon emission computer tomography (SPECT)
      and serum BDNF levels in patients with parkinsonism. Twenty-one patients with
      abnormal in vivo striatal dopamine transporter (DAT) binding as evidenced with
      [(123)I]PE2I SPECT brain scanning were included. Samples for serum BDNF levels
      were collected at the time of the SPECT scanning, and BDNF was measured with
      enzyme-linked immunosorbent assay (ELISA). The striatal binding potential of non
      displaceable [(123)I]PE2I was calculated. We found a positive correlation between
      serum BDNF levels and striatal DAT availability (p < 0.01, R(2) = 0.36). We find
      that in patients with striatal dopaminergic neurodegeneration serum BDNF levels
      decrease along with loss in striatal DAT binding.

PMID- 21176999
TI  - IGF-I gene variability is associated with an increased risk for AD.
AB  - Insulin-like growth factor I (IGF-I), a neuroprotective factor with a wide
      spectrum of actions in the adult brain, is involved in the pathogenesis of
      Alzheimer's disease (AD). Circulating levels of IGF-I change in AD patients and
      are implicated in the clearance of brain amyloid beta (Abeta) complexes. To
      investigate this hypothesis, we screened the IGF-I gene for various well known
      single nucleotide polymorphisms (SNPs) covering % of the gene variability in a
      population of 2352 individuals. Genetic analysis indicated different distribution
      of genotypes of 1 single nucleotide polymorphism, and 1 extended haplotype in the
      AD population compared with healthy control subjects. In particular, the
      frequency of rs972936 GG genotype was significantly greater in AD patients than
      in control subjects (63% vs. 55%). The rs972936 GG genotype was associated with
      an increased risk for disease, independently of apolipoprotein E genotype, and
      with enhanced circulating levels of IGF-I. These findings suggest that
      polymorphisms within the IGF-I gene could infer greater risk for AD through their
      effect on IGF-I levels, and confirm the physiological role IGF-I in the
      pathogenesis of AD.

PMID- 21177000
TI  - Bismuth heterocycles based on a diphenyl sulfone scaffold: synthesis and
      substituent effect on the antifungal activity against Saccharomyces cerevisiae.
AB  - A series of heterocyclic organobismuth(III) compounds 2 [ClBi(5-R-C6H(3)-2
      SO2C6H(4)-1'-): R=Me, Ph, MeO, Cl, H, t-Bu, CF3, F, Me2N] was synthesized in
      order to study the relative importance of structure and specific substitutions in
      relation to their lipophilicity and antifungal activity against the yeast
      Saccharomyces cerevisiae. A clear structure-activity relationship between the
      size of the inhibition zone and the value of ClogP was found for 2. These results
      suggest that the higher the lipophilicity, the lower the antifungal activity.
      Thus, 2e (R=H) and 2h (R=F), which had ClogP values of 1.18 and 1.45,
      respectively, were most active. In contrast, 2b (R=Ph) and 2f (R=t-Bu) had ClogP
      values of 3.06 and 3.00, respectively, and exhibited no antifungal activity.
      Compound 6b ClBi[5-(OH)C6H(3)-2-SO(2)-5'-(OH)C6H(3)-1'-] had an estimated ClogP
      value of 0.81 but exhibited only low activity in spite of its low ClogP value,
      suggesting that such a considerable decrease in lipophilicity lowers inhibition
      activity. Bismuth carboxylate 7b derived from p-nitrobenzoic acid and 2e
      exhibited inhibition activity comparable to those of 2e and 2h despite its higher
      lipophilicity (ClogP=2.68).

PMID- 21177001
TI  - Synthesis and antimicrobial activity of highly functionalised novel beta-lactam
      grafted spiropyrrolidines and pyrrolizidines.
AB  - A facile and one-pot synthesis of a series of novel
      spiropyrrolidines/pyrrolizidines with beta-lactam substituent has been
      accomplished through 1,3-dipolar cycloaddition reaction of alkenyl esters derived
      from beta-lactam aldehyde as dipolarophile with the dipole azomethine ylide
      derived from 1,2- and 1,3-diketones and secondary amino acids. The synthesized
      compounds were evaluated for antimicrobial activities and found to exhibit
      relatively good antibacterial activity at lower concentration against four human
      bacterial pathogens.

PMID- 21177002
TI  - Is it prudent to add n-3 long-chain polyunsaturated fatty acids to paediatric
      enteral tube feeding?
AB  - Nutritional support, as complete enteral tube feeding, is needed by many
      paediatric patients and must provide sufficient nutrients for normal growth and
      development. Enteral feeds contain the parent essential fatty acids, linoleic
      acid and alpha-linolenic acid, but often do not contain n-3 long-chain
      polyunsaturated fatty acids. Available data suggest that biosynthesis of
      eicosapentaenoic acid and docosahexaenoic acid from alpha-linolenic acid is low
      in humans and varies between individuals. Long-term enteral feeding with formulae
      devoid of eicosapentaenoic acid and docosahexaenoic acid may result in low levels
      in plasma and tissues, potentially affecting immune and neurological function.
      Currently there is insufficient evidence to define the quantitative
      eicosapentaenoic acid and docosahexaenoic acid requirements for healthy children,
      or those with various disease states. Nevertheless, it appears prudent to supply
      children on long-term enteral nutrition with a dietary source of eicosapentaenoic
      acid and docosahexaenoic acid. A reasonable approach would be to provide amounts
      matching intakes of healthy children complying with the advice to consume 1-2
      portions of oily fish per week. Further studies are needed to investigate the
      effects of different amounts of eicosapentaenoic acid and/or docosahexaenoic acid
      in enteral nutrition on polyunsaturated fatty acid status and the functional and
      clinical consequences in children.

PMID- 21177003
TI  - Level and origin of 129I and 137Cs in lichen samples (Cladonia alpestris) in
      central Sweden.
AB  - Lichen is a symbiosis between algae and fungi. They have for decades been used as
      bioindicators for atmospheric deposition of heavy metals, organic compounds and
      radioactive elements. Especially the species Cladonia alpestris and Cladonia
      rangiferina are important for the food chain lichen-reindeer-man. The
      concentration of (129)I was determined in lichen samples (Cladonia alpestris)
      contaminated by fallout from atmospheric nuclear tests explosions and the
      Chernobyl accident. The samples were collected at Lake Rogen District (62.3
      degrees N, 12.4 degrees E) in central Sweden in the periods 1961-1975 and 1987
      1998, and analysed with accelerator mass spectrometry (AMS) at CNA (Seville) to
      study its distribution in different layers. Data on the (137)Cs activity measured
      previously were also included in this study. The (129)I concentration ranged from
      (0.95 +/- 0.13) * 10(8) at g(-1) in 1961 in the uppermost layer to (14.2 +/- 0.5)
      * 10(8) at g(-1) in 1987 in deepest layer. The (129)I/(137)Cs atom ratio ranged
      between 0.12 and 0.27 for lichen samples collected in the period 1961-1975,
      indicating weapons tests fallout. For lichen samples collected between 1987 and
      1998 the behaviour of (137)Cs concentrations reflected Chernobyl fallout. The
      concentrations of the two radionuclides followed each other quite well in the
      profile, reflecting the same origin for both. From the point of view of the
      spatial distribution in the lichen, it appears that (129)I was predominantly
      accumulated in the lowest layer, the opposite to (137)Cs for which the highest
      amounts were detected systematically in the topmost layer of lichen. This
      vertical distribution is important for radioecology because lichen is the initial
      link in the food chain lichen-reindeer-man, and reindeer only graze the upper
      parts of lichen carpets.

PMID- 21177004
TI  - Cryoanalgesia in the management of intractable pain in the temporomandibular
      joint: a five-year retrospective review.
AB  - Cryoanalgesia is a controversial adjunct to the management of chronic pain, but
      we know of no studies that have investigated its effect in the management of
      temporomandibular joint (TMJ) pain. In this five-year retrospective study we
      treated 17 patients who had severe pain that had failed to respond to all forms
      of conventional conservative treatment and were not appropriate for simple open
      operation. None had a clear indication for open operation on the joint or had too
      severe disease to warrant a simple procedure. Preliminary diagnostic injections
      of bupivacaine to the TMJ relieved the pain. We applied the cryoprobe in the
      region of the auriculotemporal nerve and TMJ capsule. There was a small but
      insignificant improvement in mean mouth opening together with a significant
      (p=0.000) improvement in visual analogue pain scores (VAS) from 6.8 (range 4-10)
      to 2.0 (range 0-7). Two patients had no change in their pain scores, and 2 had
      complete resolution of their pain. The mean number of pain-free months after
      treatment was 7 (IQR 3-15). Three patients had long-term pain relief, and 12
      temporary relief; 6 of these subsequently had successful relief after total
      replacement of the TMJ. One patient had further cryoanalgesia, one was referred
      for specialist pain management, and one controlled the pain with nortriptyline.
      Of the 17 cases studied, 2 had temporary complications after cryoanalgesia.
      Cryoanalgesia is a useful adjunct to the management of intractable pain in the
      TMJ. Short-term pain relief can be achieved, and long-term relief is possible in
      some, deferring more complex and costly treatments.

PMID- 21177005
TI  - Biomechanical evaluation of a titanium implant surface conditioned by a hydroxide
      ion solution.
AB  - Two groups of titanium dental implants, identical in geometry but different in
      the treatment of their surfaces, were tested in an in vivo minipig model of the
      mandible. The surfaces that were tested were, first, sandblasted and acid-etched;
      and secondly, sandblasted, acid-etched, and conditioned. The removal torque was
      assessed at 2, 4, and 8 weeks after implantation (n=6 animals in each healing
      period). The interfacial stiffness was also evaluated. All dental implants were
      well-integrated at the time of death. Removal torque values increased
      significantly over the course of 8 weeks. Removal torque and interfacial
      stiffness were increased for conditioned surfaces after 2 weeks, but there were
      no significant differences between the two surfaces. The sandblasted and acid
      etched implants are the standard, and conditioning of the surface showed a
      tendency to increase early peri-implant formation of bone.

PMID- 21177006
TI  - A novel method of managing persistent parotid sialocele.
AB  - Sialocele formation is a recognised complication of parotid surgery. The initial
      management is usually conservative and often effective. We present a novel method
      that utilises an intra-oral approach and pig-tail catheter for safely and rapidly
      draining a large persistent sialocele. It is particularly appropriate when other
      methods have failed and the skin is at risk of breakdown.

PMID- 21177007
TI  - Greater Q angle may not be a risk factor of patellofemoral pain syndrome.
AB  - BACKGROUND: A greater Q-angle has been suggested as a risk factor for
      Patellofemoral Pain Syndrome. Greater frontal plane knee moment and impulse have
      been found to play a functional role in the onset of Patellofemoral Pain Syndrome
      in a running population. Therefore, the purpose of this investigation was to
      determine the relationship between Q-angle and the magnitude of knee abduction
      moment and impulse during running. METHODS: Q-angle was statically measured,
      using a goniometer from three markers on the anterior superior iliac spine, the
      midpoint of the patella and the tibial tuberosity. Thirty-one recreational
      runners (21 males and 10 females) performed 8-10 trials running at 4m/s (SD 0.2)
      on a 30m-runway. Absolute and normalized knee moment and impulse were calculated
      and correlated with Q-angle. FINDINGS: Negative correlations between Q-angle and
      the magnitude of peak knee abduction moment (R2=0.2444, R=-0.4944, P=0.005) and
      impulse (R2=0.2563, R=-0.5063, P=0.004) were found. Additionally, negative
      correlations between Q-angle and the magnitude of weight normalized knee
      abduction moment (R2=0.1842, R=-0.4292, P=0.016) and impulse (R2=0.2304, R=
      0.4801, P=0.006) were found. INTERPRETATION: The findings indicate that greater Q
      angle, which is actually associated with decreased frontal plane knee abduction
      moment and impulse during running, may not be a risk factor of Patellofemoral
      Pain Syndrome.

PMID- 21177008
TI  - Nano-TiO2 enhances the toxicity of copper in natural water to Daphnia magna.
AB  - The acute toxicity of engineered nanoparticles (NPs) in aquatic environments at
      high concentrations has been well-established. This study demonstrates that, at a
      concentration generally considered to be safe in the environment, nano-TiO(2)
      remarkably enhanced the toxicity of copper to Daphnia magna by increasing the
      copper bioaccumulation. Specifically, at 2 mg L(-1) nano-TiO(2), the (LC(50)) of
      Cu(2+) concentration observed to kill half the population, decreased from 111 MUg
      L(-1) to 42 MUg L(-1). Correspondingly, the level of metallothionein decreased
      from 135 MUg g(-1) wet weight to 99 MUg g(-1) wet weight at a Cu(2+) level of 100
      MUg L(-1). The copper was found to be adsorbed onto the nano-TiO(2), and ingested
      and accumulated in the animals, thereby causing toxic injury. The nano-TiO(2) may
      compete for free copper ions with sulfhydryl groups, causing the inhibition of
      the detoxification by metallothioneins.

PMID- 21177009
TI  - Combining polar organic chemical integrative samplers (POCIS) with toxicity
      testing to evaluate pesticide mixture effects on natural phototrophic biofilms.
AB  - Polar organic chemical integrative samplers (POCIS) are valuable tools in passive
      sampling methods for monitoring polar organic pesticides in freshwaters.
      Pesticides extracted from the environment using such methods can be used to
      toxicity tests. This study evaluated the acute effects of POCIS extracts on
      natural phototrophic biofilm communities. Our results demonstrate an effect of
      POCIS pesticide mixtures on chlorophyll a fluorescence, photosynthetic efficiency
      and community structure. Nevertheless, the range of biofilm responses differs
      according to origin of the biofilms tested, revealing spatial variations in the
      sensitivity of natural communities in the studied stream. Combining passive
      sampler extracts with community-level toxicity tests offers promising
      perspectives for ecological risk assessment.

PMID- 21177010
TI  - Ozone flux over a Norway spruce forest and correlation with net ecosystem
      production.
AB  - Daily ozone deposition flux to a Norway spruce forest in Czech Republic was
      measured using the gradient method in July and August 2008. Results were in good
      agreement with a deposition flux model. The mean daily stomatal uptake of ozone
      was around 47% of total deposition. Average deposition velocity was 0.39 cm s(-1)
      and 0.36 cm s(-1) by the gradient method and the deposition model, respectively.
      Measured and modelled non-stomatal uptake was around 0.2 cm s(-1). In addition,
      net ecosystem production (NEP) was measured by using Eddy Covariance and
      correlations with O3 concentrations at 15 m a.g.l., total deposition and stomatal
      uptake were tested. Total deposition and stomatal uptake of ozone significantly
      decreased NEP, especially by high intensities of solar radiation.

PMID- 21177011
TI  - Association of long-term administration of the survivin mRNA-targeted antisense
      oligonucleotide LY2181308 with reversible kidney injury in a patient with
      metastatic melanoma.
AB  - A 57-year-old man with metastatic melanoma was treated with the survivin
      inhibitor and antisense oligonucleotide LY2181308 as part of a First-in-Human
      Dose trial. After 18 months of treatment, he developed kidney injury and the
      treatment was discontinued. At 9 months and before the development of kidney
      injury, LY2181308 concentrations were 8- to 10-fold higher relative to median
      predicted values, but within the targeted exposure considered to be safe.
      However, at 17 months, 28 days after stopping LY2181308 therapy, LY2181308
      concentration exceeded the predicted range by 38-fold. His decreased kidney
      function was slow to improve after stopping treatment. A kidney biopsy showed
      signs of acute tubular injury with regeneration. Complete recovery of kidney
      function occurred 6 months after treatment was stopped. The relationship between
      high exposures and slow LY2181308 clearance with the gradual improvement in
      kidney function after stopping the antisense treatment suggests that the
      oligonucleotide was related to the kidney injury. Based on this case report,
      kidney function should be monitored frequently in patients receiving long-term
      treatment with antisense oligonucleotides that specifically target survivin,
      particularly when they receive concomitant angiotensin-converting enzyme
      inhibitors or nonsteroidal anti-inflammatory drugs.

PMID- 21177012
TI  - Relationship between periodontal disease and mortality in patients treated with
      maintenance hemodialysis.
AB  - BACKGROUND: The relationship between periodontitis and outcomes in patients
      treated with long-term hemodialysis is controversial. Our previous work suggests
      that periodontitis is associated with malnutrition and inflammation. Here, we
      hypothesize that periodontitis is associated with mortality in hemodialysis
      patients. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS:
      253 patients undergoing hemodialysis at a single hospital-based dialysis
      facility. PREDICTOR: Severity of periodontal disease (mild, moderate, or severe
      based on oral examination of 6 teeth). OUTCOMES & MEASUREMENTS: All-cause and
      cardiovascular mortality during a 6-year follow-up after an oral health
      examination of index teeth. RESULTS: During the 6-year follow-up, 102 patients
      died. Death occurred in 70.6%, 41.8%, and 24.0% of patients with severe,
      moderate, and mild/no periodontitis, respectively. Using mild/no periodontitis as
      the reference group and adjustment for demographic characteristics, comorbid
      conditions, and selected laboratory values, HRs for all-cause mortality were 1.39
      (95% CI, 0.83-2.34) and 1.83 (95% CI, 1.04-3.24) for moderate and severe
      periodontitis, respectively. HRs for cardiovascular mortality were not
      statistically significant. LIMITATIONS: Single assessment of periodontal disease
      severity. CONCLUSIONS: For patients undergoing long-term hemodialysis,
      periodontitis is associated with increased risk of death. Clinical trials are
      required to determine whether treatment of periodontitis decreases mortality.

PMID- 21177013
TI  - Short-term outcomes of induction therapy with tacrolimus versus cyclophosphamide
      for active lupus nephritis: A multicenter randomized clinical trial.
AB  - BACKGROUND: Intravenous cyclophosphamide with prednisone is an effective
      treatment for lupus nephritis, but with significant toxicities. We compared the
      efficacy and safety of tacrolimus versus intravenous cyclophosphamide as
      induction therapy. STUDY DESIGN: Multicenter noninferiority randomized controlled
      trial. SETTING & PARTICIPANTS: 81 patients with biopsy-proven lupus nephritis
      from 9 nephrology centers in China from 2006-2008. INTERVENTION: Prednisone and
      either tacrolimus (n = 42) or intravenous cyclophosphamide (n = 39) for 6 months.
      Tacrolimus was started at 0.05 mg/kg/d and titrated to achieve a trough blood
      concentration of 5-10 ng/mL. Intravenous cyclophosphamide was initiated at 750
      mg/m2 of body surface area, then adjusted to 500-1,000 mg/m2 every 4 weeks for a
      total of 6 pulse treatments. OUTCOMES & MEASUREMENTS: The primary outcome was
      complete remission (proteinuria with protein excretion <0.3 g/24 h, serum albumin
      >=3.5 g/dL, normal urinary sediment, and normal or stable serum creatinine level)
      at 6 months. Response (complete or partial remission), clinical parameters, and
      adverse effects were secondary end points. RESULTS: After the 6-month induction
      therapy, the tacrolimus group achieved higher cumulative probabilities of
      complete remission and response (52.4% vs 38.5% and 90.5% vs 82.1%, respectively)
      than the intravenous cyclophosphamide group, but differences were not
      statistically significant (log-rank test, P = 0.2 and P = 0.7, respectively).
      Proteinuria [corrected] was significantly decreased in tacrolimus- versus
      intravenous cyclophosphamide-treated patients after the first month of treatment,
      even with adjustment for baseline proteinuria (protein excretion, 1.76 vs 2.40
      g/d; P = 0.02 for the log-transformed analysis). [corrected] After treatment,
      serum creatinine levels and estimated glomerular filtration rates were not
      significantly different between treatment groups. Adverse effects, such as
      leukopenia and gastrointestinal symptoms, were less frequent in the tacrolimus
      group. LIMITATIONS: Nonblinded, small sample size, and short duration of follow
      up. CONCLUSIONS: In conjunction with prednisone, induction therapy with
      tacrolimus is at least as efficacious as intravenous cyclophosphamide and
      prednisone in producing complete remission of lupus nephritis and has a more
      favorable safety profile.

PMID- 21177014
TI  - Monitoring myocardial recovery during induced hypothermia with a disposable
      monoplane TEE probe.
AB  - A 73 year old female with a history coronary artery bypass grafting and coronary
      stents had a witnessed cardiac arrest at home. She was transferred to an outside
      hospital and emergency heart catheterization revealed patent LIMA to LAD, stented
      grafts open, and no new culprit lesions. A temporary transvenous pacing wire was
      placed for bradycardia. She was transferred to the ICU where she was sedated and
      paralyzed for induction of hypothermia approximately five hours after the arrest.
      A miniaturized disposable TEE probe (Photo 1) was placed to allow ongoing
      monitoring of cardiac function and intravascular volume.

PMID- 21177015
TI  - Effect of therapeutic hypothermia vs delta-opioid receptor agonist on post
      resuscitation myocardial function in a rat model of CPR.
AB  - AIM: This study is to compare the effect of the delta-opioid receptor agonist, D
      Ala(2)-D-Leu(5) enkephalin (DADLE) with normothermic control and therapeutic
      hypothermia on post resuscitation myocardial function and 72-h survival in a rat
      model of cardiac arrest and resuscitation. METHODS: Ventricular fibrillation (VF)
      was induced in 15 male Sprague-Dawley rats. After 8 min of untreated VF,
      cardiopulmonary resuscitation was performed for 8 min before defibrillation.
      Animals were randomized to three groups of five: (a) normothermia; (b)
      hypothermia (32  degrees C); and (c) normothermia with DADLE intravenous infusion
      (1 mg/kg h(-1)). Hypothermia and drug infusion were started after successful
      defibrillation. Myocardial functions, including cardiac output (CO), left
      ventricular ejection fraction (LVEF), and myocardial performance index (MPI) were
      measured echocardiographically together with duration of survival. RESULTS: The
      72-h survival was significantly greater in the hypothermic group than in both
      DADLE and normothermic group (p = 0.02). However, the survival time of the DADLE
      treated animals was significantly longer than that of the normothermia group
      (51.8 +/- 18.9 vs 18.8 +/- 10.1h, p < 0.01). DADLE group showed significantly
      better CO (PR 60 min, p = 0.049), better LVEF (PR 60 min, p = 0.044; PR 240 min,
      p < 0.001) and lower MPI (PR 60 min, p = 0.043; PR 240 min, p = 0.045) than
      normothermic group. Hypothermia group also showed significantly better CO (PR 60m
      in, p = 0.044; PR 240 min, p = 0.007), better LVEF (PR 60 min, p = 0.001; PR 240
      min, p < 0.001) and lower MPI (PR 60 min, p = 0.003; PR 240 min, p = 0.012) than
      the normothermic group. CONCLUSIONS: DADLE attenuated post resuscitation
      myocardial dysfunction and increased short term survival time. However, the 72-h
      survival in the DADLE group was less than that in the hypothermia group.

PMID- 21177016
TI  - Supraphysiological estrogen levels adversely impact proliferation and histone
      modification in human embryonic stem cells: possible implications for controlled
      ovarian hyperstimulation assisted pregnancy.
AB  - OBJECTIVE: Controlled ovarian hyperstimulation (COH) results in supraphysiologic
      levels of maternal serum estradiol (E(2)) during the luteal phase, thus promoting
      oocyte production at unknown risk to the subsequently developing embryo. Human
      embryonic stem cells (hESCs) have been identified as a model system to assess the
      impact of COH on early embryonic development, specifically 17beta-estradiol
      mediated effects on proliferation, gene expression, and histone modification.
      STUDY DESIGN: Cell proliferation and associated factors, such as HDAC1, as well
      as histone modification patterns were evaluated in ERalpha and beta expressing
      hESCs after exposure to 17beta-estradiol (1*10(-10) M to 1*10(-7) M), as well as
      in an untreated control. RESULTS: Resultant data revealed that while
      physiologically relevant E(2) levels (1*10(-9)M E(2)) induced cell cycle
      progression from G1 to the proliferation phase, supraphysiologic levels akin to
      those observed after COH (1*10(-7) M E(2)) adversely affected hESCs proliferation
      via down regulation of HDAC1. Modification of H3K9me2, PhH3S10, H4K5ac, and H2A.Z
      histone patterns were also dependent on 17beta-estradiol concentration.
      CONCLUSION: While physiologic levels of 17beta-estradiol induced cell
      proliferation, possibly via HDAC1 involvement in histone modification, cell
      proliferation in hESCs was suppressed at supraphysiologic levels.

PMID- 21177017
TI  - Periodic solutions and refractory periods in the soliton theory for nerves and
      the locust femoral nerve.
AB  - Close to melting transitions it is possible to propagate solitary
      electromechanical pulses which reflect many of the experimental features of the
      nerve pulse including mechanical dislocations and reversible heat production.
      Here we show that one also obtains the possibility of periodic pulse generation
      when the constraint for the nerve is the conservation of the overall length of
      the nerve. This condition generates an undershoot beneath the baseline
      ('hyperpolarization') and a 'refractory period', i.e., a minimum distance between
      pulses. In this paper, we outline the theory for periodic solutions to the wave
      equation and compare these results to action potentials from the femoral nerve of
      the locust (Locusta migratoria). In particular, we describe the frequently
      occurring minimum-distance doublet pulses seen in these neurons and compare them
      to the periodic pulse solutions.

PMID- 21177018
TI  - Preparation of porous nano-calcium titanate microspheres and its adsorption
      behavior for heavy metal ion in water.
AB  - Using D311 resin as a template, porous nano-calcium titanate microspheres (PCTOM)
      were prepared by a citric acid complex sol-gel method and characterized by X-ray
      diffraction (XRD), SEM and FTIR. The method's adsorption capabilities for heavy
      metal ions such as lead, cadmium and zinc were studied and adsorption and elution
      conditions were investigated. Moreover, taking the cadmium ion as an example, the
      thermodynamics and kinetics of the adsorption were studied. The results show that
      the microspheres were porous and were made of perovskite nano-calcium titanate.
      The lead, cadmium and zinc ions studied could be quantitatively retained at a pH
      value range of 5-8. The adsorption capacities of PCTOM for lead, cadmium and zinc
      were found to be 141.8 mg g(-1), 18.0 mg g(-1) and 24.4 mg g(-1) respectively.
      The adsorption behavior followed a Langmuir adsorption isotherm and a pseudo
      second-order kinetic model, where adsorption was an endothermic and spontaneous
      physical process. The adsorbed metal ions could be completely eluted using 2 mol
      L(-1) HNO(3) with preconcentration factors over 100 for all studied heavy metal
      ions. The method has also been applied to the preconcentration and FAAS
      determination of trace lead, cadmium and zinc ion in water samples with
      satisfactory results.

PMID- 21177019
TI  - Effect of iron doping into CeO2-ZrO2 on the properties and catalytic behaviour of
      Pd-only three-way catalyst for automotive emission control.
AB  - Ce(0.67)Zr(0.33)O(2) doped with iron oxide was prepared and the corresponding Pd
      only three-way catalysts were examined and characterized. Pd/CZFe(1%) catalyst
      exhibits the best catalytic performance for CO, HC, NO and NO(2) elimination and
      the widest operation window. The doping of iron oxide with 1% loading suggests
      the formation of more homogeneous Ce-Zr-Fe-O ternary solid solution, which seems
      to facilitate the reduction of Ce(4+)->Ce(3+) or the formation of oxygen vacancy
      and to promote the interaction between Ce-Zr and Fe. Moreover, the Ce redox
      behaviour for surface reduction suggests depending not only on the formation of
      homogeneous Ce-Zr-Fe-O but also on the surface property of the sample. The
      increase in the concentration of oxygen vacancies under all atmospheres for
      CZFe(1%) sample also results in the enhancement of oxygen storage complete
      capacity.

PMID- 21177020
TI  - Photocatalytic degradation of monocrotophos pesticide--an endocrine disruptor by
      magnesium doped titania.
AB  - Mg-doped TiO(2) with different Mg concentrations were prepared using sol-gel
      method and characterized by XRD, UV-visible, XPS, SEM and FT-IR. The XRD results
      revealed that Mg(2+) goes into the TiO(2) lattice. SEM images of the doped and
      pure TiO(2) indicated that there is a smaller particle size for the doped
      catalyst compared to that of the pure TiO(2). UV-visible absorption spectra
      indicated that upon doping with Mg(2+) ion, the catalyst exhibits absorption in
      visible region. FT-IR and XPS spectra demonstrated that the presence of Mg(2+)
      ion in the TiO(2) lattice as substitutional dopant. Photocatalytic activity of
      doped TiO(2) has been evaluated by degradation of the monocrotophos (MCP)
      pesticide. The effect of solution pH, catalyst dosage and initial concentration
      of MCP on the photocatalytic activity of Mg-doped TiO(2) with different loadings
      was studied. It was observed that the rate of degradation of MCP over Mg-doped
      TiO(2) is better than Pure TiO(2) and Degussa P-25.

PMID- 21177021
TI  - Laser induced photocatalytic degradation of hazardous dye (Safranin-O) using self
      synthesized nanocrystalline WO3.
AB  - The photocatalytic degradation of Safranin-O (known as Basic Red 2) in water
      using locally synthesized nanocrystalline WO(3) as a photocatalyst was
      investigated under UV laser irradiation. The photo-oxidation removal of the dye
      was monitored by UV-vis spectrophotometer. The blank experiments for either laser
      irradiated only Safranin-O solution or the suspension containing WO(3) and
      Safranin-O in the dark showed that both laser illumination and the photocatalyst
      were essential for the removal of Safranin-O. The effect of experimental
      parameters including laser energy, catalyst loading, solution pH and the initial
      dye concentration on photocatalytic degradation of Basic Red 2 were also
      investigated. Results indicate that the rate of reaction is strongly influenced
      by the adsorption of an azo dye into the surface of the photocatalyst materials
      and suggests an optimum catalyst loading and dye concentration for the
      degradation reaction. It was investigated that the adsorption of the dye
      decreases at higher alkaline pH because both catalyst and substrate are
      negatively charged, developing repulsive forces between them. Kinetic data
      obtained reveals that the rate of the reaction obeys the first-order kinetics.

PMID- 21177022
TI  - Biodegradation pathways of chloroanilines by Acinetobacter baylyi strain GFJ2.
AB  - The Acinetobacter baylyi strain GFJ2 was isolated from soil that was potentially
      contaminated with herbicides. It exhibited complete biodegradations of 4
      chlroaniline (4CA) and 3,4-dichloroaniline (34DCA), a wide range of
      monohalogenated anilines (chloro-, bromo-, and fluoro-anilines) and other
      dichloroanilines. An in-depth investigation of the biodegradation pathway
      revealed that a dechlorination reaction may be involved in 34DCA biodegradation,
      which forms 4CA as the first intermediate. By detecting the transient
      intermediates and characterizing the relevant enzymes, this investigation is also
      the first to report that A. baylyi strain GFJ2 has two distinct 4CA degradation
      pathways that yield 4-chlorocatechol (4CC) and aniline as the first intermediate
      in each route, which are further metabolized through an ortho-cleavage pathway.
      Analysis of biodegradation kinetics analysis illustrated that A. baylyi GFJ2
      utilized aniline and 4CC at significantly slower rates than it used 4CA,
      suggesting that the transformations of aniline and 4CC were probably the limiting
      steps during 4CA biodegradation. Our results suggest the potential application of
      A. baylyi strain GFJ2 in bioremediation and waste treatment, and the kinetic data
      provide the insights into the degradation mechanism, dynamics and possible
      limitations of the biodegradation which include substrate and product
      inhibitions.

PMID- 21177023
TI  - Precious metal recovery by selective adsorption using biosorbents.
AB  - Silk sericin and chitosan biosorbents are low cost and highly efficient
      biosorbents derived from waste biomass. Both biosorbents displayed good capacity
      and excellent selectivity for gold adsorption. Silk sericin and chitosan adsorbed
      respectively 1 and 3.3mmolg(-1) of gold and have K(d) values of 450 and 34,000,
      respectively. Experimental evidence showed that gold adsorbed on the amide groups
      of the silk sericin, while gold and copper adsorbed on the amino groups of
      chitosan via charge-interactions and complexation. Binary (Au-Cu), five (Au-Co-Ni
      Cu-Zn) and six (Au-Pd-Co-Ni-Cu-Zn) component separations consistently showed that
      silk sericin has better selectivity (Sel(Au)>2.4) than chitosan. It is possible
      to recover gold at 99.5% purity by silk sericin and 90% if the solution contained
      palladium.

PMID- 21177024
TI  - Beta zeolite supported sol-gel TiO2 materials for gas phase photocatalytic
      applications.
AB  - Beta zeolite supported sol-gel TiO(2) photocatalytic materials were prepared
      according to a sol-gel route in which high specific surface area Beta zeolite
      powder was incorporated into the titanium isopropoxide sol during the course of
      the sol-gel process. This led to an intimate contact between the zeolite surface
      and the TiO(2) precursors, and resulted in the anchorage of large amounts of
      dispersed TiO(2) nanoparticles and in the stabilization of TiO(2) in its anatase
      form, even for high TiO(2) wt. contents and high calcination temperatures. Taking
      the UV-A photocatalytic oxidation of methanol as gas phase target reaction, high
      methanol conversions were obtained on the Beta zeolite supported TiO(2)
      photocatalysts when compared to bulk sol-gel TiO(2), despite lower amounts of
      TiO(2) within the photoactive materials. The methanol conversion was optimum for
      about 40 wt.% TiO(2) loading and calcination temperatures of 500-600 degrees C.

PMID- 21177025
TI  - Lentinus (Panus) tigrinus augmentation of a historically contaminated soil:
      matrix decontamination and structure and function of the resident bacterial
      community.
AB  - The ability of Lentinus tigrinus to grow and to degrade persistent aromatic
      hydrocarbons in aged contaminated soil was assessed in this study. L. tigrinus
      extensively colonized the soil; its degradation activity after 60 d incubation at
      28 degrees C, however, was mostly limited to dichloroaniline isomers,
      polychlorinated benzenes and diphenyl ether while the fungus was unable to
      deplete 9,10-anthracenedione and 7-H-benz[DE]anthracene-7-one which were the
      major soil contaminants. Although clean-up levels were limited, both density of
      cultivable heterotrophic bacteria and richness of the resident bacterial
      community in L. tigrinus microcosms (LtM) increased over time to a significantly
      larger extent than the respective amended incubation controls (1.9*10(9) CFU g(
      1) vs. 1.0*10(9) CFU g(-1) and 37 vs. 16, respectively). Naphthalene- and
      catechol 2,3-dioxygenase gene copy numbers, however, decreased over time at a
      higher rate in LtM than in incubation controls likely due to a higher stimulation
      on heterotrophs than xenobiotics-degrading community members.

PMID- 21177026
TI  - Poly(vinyl) chloride membrane copper-selective electrode based on 1-phenyl-2-(2
      hydroxyphenylhydrazo)butane-1,3-dione.
AB  - 1-Phenyl-2-(2-hydroxyphenylhydrazo)butane-1,3-dione (H(2)L) was used as an
      effective ionophore for copper-selective poly(vinyl) chloride (PVC) membrane
      electrodes. Optimization of the composition of the membrane and of the conditions
      of the analysis was performed, and under the optimized conditions the electrode
      has a detection limit of 6.30*10(-7) M Cu(II) at pH 4.0 with response time 10s
      and displays a linear EMF versus log[Cu(2+)] response over the concentration
      range 2.0*10(-6) to 5.0*10(-3) M Cu(II) with a Nernstian slope of 28.80+/-0.11
      mV/decade over the pH range of 3.0-8.0. The sensor is stable for 9 weeks and
      exhibits good selectivity with respect to alkali, alkali earth and transition
      metal ions (e.g. Na(+), K(+), Ba(2+), Ca(2+), Zn(2+), Cd(2+), Co(2+), Mn(2+),
      Ni(2+), Fe(2+), Al(3+)) in the 3.0-8.0 pH range. It was successfully applied for
      the direct determination of copper(II) in zinc, aluminum and nickel based alloys,
      in soils polluted by oil, and as an indicator electrode for potentiometric
      titration of copper ions with EDTA.

PMID- 21177027
TI  - Influence of Rhizobium meliloti on phytoremediation of polycyclic aromatic
      hydrocarbons by alfalfa in an aged contaminated soil.
AB  - Microbe-assisted phytoremediation is emerging as one of the most effective means
      by which plants and their associated rhizosphere microbes degrade organic
      contaminants in soils. A pot study was conducted to examine the effects of
      inoculation with Rhizobium meliloti on phytoremediation by alfalfa grown for 90
      days in an agricultural soil contaminated with weathered polycyclic aromatic
      hydrocarbons (PAHs). Planting with uninoculated alfalfa (P) and alfalfa
      inoculated with R. meliloti (PR) significantly lowered the initial soil PAH
      concentrations by 37.2 and 51.4% respectively compared with unplanted control
      soil. Inoculation with R. meliloti significantly increased the counts of
      culturable PAH-degrading bacteria, soil microbial activity and the carbon
      utilization ability of the soil microbial community. The results suggest that the
      symbiotic association between alfalfa and Rhizobium can stimulate the rhizosphere
      microflora to degrade PAHs and its application may be a promising bioremediation
      strategy for aged PAH-contaminated soils.

PMID- 21177028
TI  - Photocatalytic reduction of Cr(VI) on the new hetero-system CuAl2O4/TiO2.
AB  - Visible light driven HCrO(4)(-) reduction was successfully achieved over the new
      hetero-system CuAl(2)O(4)/TiO(2). The spinel, elaborated by nitrate route, was
      characterized photo electrochemically. The optical gap was found to be 1.70 eV
      and the transition is directly allowed. The conduction band (-1.05 V(SCE)) is
      located below that of TiO(2), more negative than the HCrO(4)(-)/Cr(3+) level
      (+0.58 V(SCE)) yielding a thermodynamically feasible chromate reduction upon
      visible illumination. CuAl(2)O(4) is stable against photo corrosion by holes
      consumption reaction involving salicylic acid which favors the charges
      separation. There is a direct correlation between the dark adsorption and the
      photo activity. A reduction of more than 95% of chromate was achieved after 3 h
      irradiation at pH 2 with an optimal mass ratio (CuAl(2)O(4)/TiO(2)) equal to 1/3.
      The reduction follows a first order kinetic with a half life of ~1 h and a
      quantum yield of 0.11% under polychromatic light. Prolonged illumination was
      accompanied by a deceleration of the Cr(VI) reduction thanks to the competitive
      water discharge. The hydrogen evolution, an issue of energetic concern, took
      place with a rate of 3.75 cm(3) (g catalyst)(-1) h(-1).

PMID- 21177029
TI  - Defluoridation from aqueous solutions by nano-alumina: characterization and
      sorption studies.
AB  - The present study was conducted to evaluate the feasibility of nano-alumina
      (Al(2)O(3)) for fluoride adsorption from aqueous solutions. The nature and
      morphology of pure and fluoride-sorbed nano-alumina were characterized by SEM
      with EDX, XRD, and FTIR analysis. Batch adsorption studies were performed as a
      function of contact time, initial fluoride concentration, temperature, pH and
      influence of competing anions. Fluoride sorption kinetics was well fitted by
      pseudo-second-order model. The maximum sorption capacity of nano-alumina for
      fluoride removal was found to be 14.0 mg g(-1) at 25 degrees C. Maximum fluoride
      removal occurred at pH 6.15. The fluoride sorption has been well explained using
      Langmuir isotherm model. Fluoride sorption was mainly influenced by the presence
      of PO(4)(3-), SO(4)(2-) and CO(3)(2-) ions.

PMID- 21177030
TI  - Regeneration of three-way automobile catalysts using biodegradable metal
      chelating agent--S, S-ethylenediamine disuccinic acid (S, S-EDDS).
AB  - Regeneration of the activity of three-way catalytic converters (TWCs) was tested
      for the first time using a biodegradable metal chelating agent (S, S
      ethylenediamine disuccinic acid (S, S-EDDS). The efficiency of this novel
      environmentally friendly solvent in removing various contaminants such as P, Zn,
      Pb, Cu and S from commercial aged three-way catalysts, and improving their
      catalytic performance towards CO and NO pollutants removal has been investigated.
      Four samples of catalysts from the front and rear inlets of two different TWCs
      with different mileages and aged under completely different driving conditions
      were investigated. The catalysts were characterized using various techniques,
      such as X-ray diffraction (XRD), Scanning electron microscopy (SEM), and Brunauer
      Emmett-Teller (BET) surface area measurements (N(2) adsorption at 77 K).
      Quantitative ICP-MS analyses and SEM-EDS studies show the removal of Zn, P and
      Pb. SEM-EDS images obtained at low magnification (50 MUm) showed considerable
      differences in the surface morphology and composition after washing with S, S
      EDDS. However, XRD studies indicated neither little to no removal of major
      contaminant compound phases nor major structural changes due to washing.
      Correspondingly, little or no enhancement in BET surface area was observed
      between the used and washed samples. Light-off curves show that the regeneration
      procedure employed can effectively improve the catalytic performance towards NO
      pollutant.

PMID- 21177031
TI  - Designing a reliable leak bio-detection system for natural gas pipelines.
AB  - Monitoring of natural gas (NG) pipelines is an important task for
      economical/safety operation, loss prevention and environmental protection. Timely
      and reliable leak detection of gas pipeline, therefore, plays a key role in the
      overall integrity management for the pipeline system. Owing to the various
      limitations of the currently available techniques and the surveillance area that
      needs to be covered, the research on new detector systems is still thriving.
      Biosensors are worldwide considered as a niche technology in the environmental
      market, since they afford the desired detector capabilities at low cost, provided
      they have been properly designed/developed and rationally
      placed/networked/maintained by the aid of operational research techniques. This
      paper addresses NG leakage surveillance through a robust cooperative/synergistic
      scheme between biosensors and conventional detector systems; the network is
      validated in situ and optimized in order to provide reliable information at the
      required granularity level. The proposed scheme is substantiated through a
      knowledge based approach and relies on Fuzzy Multicriteria Analysis (FMCA), for
      selecting the best biosensor design that suits both, the target analyte and the
      operational micro-environment. This approach is illustrated in the design of leak
      surveying over a pipeline network in Greece.

PMID- 21177032
TI  - Low temperature followed by matrix solid-phase dispersion-sonication procedure
      for the determination of multiclass pesticides in palm oil using LC-TOF-MS.
AB  - A simple and effective multiresidue method based on precipitation at low
      temperature followed by matrix solid-phase dispersion-sonication was developed
      and validated to determine dimethoate, malathion, carbaryl, simazine,
      terbuthylazine, atrazine and diuron in palm oil using liquid chromatography time
      of-flight mass spectrometry (LC-TOF-MS). Liquid-liquid extraction (LLE) followed
      by low temperature method were optimized by studying the effect of type and
      volume of organic solvent (acetonitrile, acetonitrile:n-hexane (3:2 v/v) and
      acetone) and time of freezing to obtain high recovery yield and low co-extract
      fat residue in the final extract. The optimal conditions for matrix solid-phase
      dispersion (MSPD) were obtained using 5 g of palm oil, 2 g of primary secondary
      amine (PSA) as dispersing sorbent, 1 g of graphitized carbon black (GCB) as clean
      up sorbent and 15 mL of acetonitrile as eluting solvent under conditions of 15
      min ultrasonication at room temperature. Method validation was performed in order
      to study sensitivity, linearity, precision, and accuracy. Average recoveries at
      three concentration levels (25, 50 and 100 MUg kg(-1)) were found in the range of
      72.6-91.3% with relative standard deviations between 5.3% and 14.2%. Detection
      and quantification limits ranged from 1.5 to 5 MUg kg(-1) and from 2.5 to 9 MUg
      kg(-1), respectively.

PMID- 21177033
TI  - High-resolution functional magnetic resonance imaging mapping of noxious heat and
      tactile activations along the central sulcus in New World monkeys.
AB  - This study mapped the fine-scale functional representation of tactile and noxious
      heat stimuli in cortical areas around the central sulcus of anesthetized squirrel
      monkeys by using high-resolution blood oxygen level-dependent (BOLD) fMRI at
      9.4T. Noxious heat (47.5 degrees C) stimulation of digits evoked multiple
      spatially distinct and focal BOLD activations. Consistent activations were
      observed in areas 3a, 3b, 1, and 2, whereas less frequent activation was present
      in M1. Compared with tactile activations, thermal nociceptive activations covered
      more area and formed multiple foci within each functional area. In general,
      noxious heat activations in area 3b did not colocalize with tactile responses.
      The spatial relationships of heat and tactile activations in areas 3a and 1/2
      varied across animals. Subsequent electrophysiological mapping confirmed that the
      evoked heat and tactile BOLD signals were somatotopically appropriate. The
      magnitude and temporal profiles of the BOLD signals to noxious heat stimuli
      differed across cortical areas. Comparatively late-peaking but stronger signals
      were observed in areas 3b and 2, whereas earlier-peaking but weaker signals were
      observed in areas 3a, 1, and M1. In sum, this study not only confirmed the
      involvement of somatosensory areas of 3a, 3b, and 1, but also identified the
      engagements of area 2 and M1 in the processing of heat nociceptive inputs.
      Differential BOLD response profiles of the individual cortical areas along the
      central sulcus suggest that these areas play different roles in the encoding of
      nociceptive inputs. Thermal nociceptive and tactile inputs may be processed by
      different clusters of neurons in different areas. To critically bridge animal and
      human pain studies, human fMRI was related to primate fMRI and electrophysiology
      of nociceptive processing, examining the functional role of the primary
      somatosensory cortex in heat nociception and demonstrating that subregion areas
      3a, 3b, 1, 2, and M1 are responsive to noxious heat stimuli.

PMID- 21177034
TI  - Effectiveness of small daily amounts of progressive resistance training for
      frequent neck/shoulder pain: randomised controlled trial.
AB  - Regular physical exercise is a cornerstone in rehabilitation programs, but
      adherence to comprehensive exercise remains low. This study determined the
      effectiveness of small daily amounts of progressive resistance training for
      relieving neck/shoulder pain in healthy adults with frequent symptoms; 174 women
      and 24 men working at least 30 h per week and with frequent neck/shoulder pain
      were randomly assigned to resistance training with elastic tubing for 2 or 12
      minutes per day 5 times per week, or weekly information on general health
      (control group). Primary outcomes were changes in intensity of neck/shoulder pain
      (scale 0 to 10), examiner-verified tenderness of the neck/shoulder muscles (total
      tenderness score of 0 to 32), and isometric muscle strength at 10 weeks. Compared
      with the control group, neck/shoulder pain and tenderness, respectively,
      decreased 1.4 points (95% confidence interval -2.0 to -0.7, p<0.0001) and 4.2
      points (95% confidence interval -5.7 to -2.7, p<0.0001) in the 2-minute group and
      1.9 points (95% confidence interval -2.5 to -1.2, p<0.0001) and 4.4 points (95%
      confidence interval -5.9 to -2.9, p<0.0001) in the 12-minute group. Compared with
      the control group, muscle strength increased 2.0 Nm (95% confidence interval 0.5
      to 3.5Nm, p=0.01) in the 2-minute group and 1.7Nm (95% confidence interval 0.2 to
      3.3 Nm, p=0.02) in the 12-minute group. In conclusion, as little as 2 minutes of
      daily progressive resistance training for 10 weeks results in clinically relevant
      reductions of pain and tenderness in healthy adults with frequent neck/shoulder
      symptoms. TRIAL REGISTRATION: www.isrctn.org/ISRCTN60264809. In generally healthy
      adults with frequent neck/shoulder muscle pain, as little as 2 minutes of daily
      progressive resistance training reduces pain and tenderness.

PMID- 21177036
TI  - Broadening the applications of the atom probe technique by ultraviolet
      femtosecond laser.
AB  - Laser assisted field evaporation using ultraviolet (UV) wavelength gives rise to
      better mass resolution and signal-to-noise ratio in atom probe mass spectra of
      metals, semiconductors and insulators compared to infrared and green lasers.
      Combined with the site specific specimen preparation techniques using the lift
      out and annular Ga ion milling in a focused ion beam machine, a wide variety of
      materials including insulating oxides can be quantitatively analyzed by the three
      dimensional atom probe using UV laser assisted field evaporation. After
      discussing laser irradiation conditions for optimized atom probe analyses, recent
      atom probe tomography results on oxides, semiconductor devices and grain
      boundaries of sintered magnets are presented.

PMID- 21177035
TI  - Identifying prescription opioid use disorder in primary care: diagnostic
      characteristics of the Current Opioid Misuse Measure (COMM).
AB  - The Current Opioid Misuse Measure (COMM), a self-report assessment of past-month
      aberrant medication-related behaviors, has been validated in specialty pain
      management patients. The performance characteristics of the COMM were evaluated
      in primary care (PC) patients with chronic pain. It was hypothesized that the
      COMM could identify patients with prescription drug use disorder (PDD). English
      speaking adults awaiting PC visits at an urban, safety-net hospital, who had
      chronic pain and had received any opioid analgesic prescription in the past year,
      were administered the COMM. The Composite International Diagnostic Interview
      served as the "gold standard," using DSM-IV criteria for PDD and other substance
      use disorders (SUDs). A receiver operating characteristic (ROC) curve
      demonstrated the COMM's diagnostic test characteristics. Of the 238 participants,
      27 (11%) met DSM-IV PDD criteria, whereas 17 (7%) had other SUDs, and 194 (82%)
      had no disorder. The mean COMM score was higher in those with PDD than among all
      others (ie, those with other SUDs or no disorder, mean 20.4 [SD 10.8] vs 8.4 [SD
      7.5], P<.0001). A COMM score of?13 had a sensitivity of 77% and a specificity of
      77% for identifying patients with PDD. The area under the ROC curve was 0.84. For
      chronic pain patients prescribed opioids, the development of PDD is an
      undesirable complication. Among PC patients with chronic pain-prescribed
      prescription opioids, the COMM is a promising tool for identifying those with
      PDD. Among primary care patients with chronic pain-prescribed opioids, the
      validated Current Opioid Misuse Measure (COMM) is a promising tool for
      identifying patients with prescription opioid use disorder.

PMID- 21177037
TI  - Revisiting Bragg's X-ray microscope: scatter based optical transient grating
      detection of pulsed ionising radiation.
AB  - Transient optical gratings for detecting ultrafast signals are routine for
      temporally resolved photochemical investigations. Many processes can contribute
      to the formation of such gratings; we indicate use of optically scattering
      centres that can be formed with highly variable latencies in different materials
      and devices using ionising radiation. Coherent light scattered by these centres
      can form the short-wavelength-to-optical-wavelength, incoherent-to-coherent basis
      of a Bragg X-ray microscope, with inherent scope for optical phasing. Depending
      on the dynamics of the medium chosen, the way is open to both ultrafast pulsed
      and integrating measurements. For experiments employing brief pulses, we discuss
      high-dynamic-range short-wavelength diffraction measurements with real-time
      optical reconstructions. Applications to optical real-time X-ray phase-retrieval
      are considered.

PMID- 21177038
TI  - Anticoccidial effects of coumestans from Eclipta alba for sustainable control of
      Eimeria tenella parasitosis in poultry production.
AB  - The aim of this study was to evaluate the anticoccidial efficacy of a product
      containing coumestans from Eclipta alba. Experimental conditions were set up as
      to reproduce the environment conditions for husbandry adopted in commercial
      broiler farms. Broilers were raised in broiler chicken shed provided with
      feeders, drinkers, illumination and temperature control systems and floor
      covering to afford an adequate nourishing environment. Male Cobb broilers (240)
      were assigned to four experimental groups being each experimental group set apart
      in rice straw-covered shed isolated with wire mesh. One-day-old broilers were
      reared in a coccidian-free environment with ad libitum supply of filtered water
      and freely available standard feed, from the 1st to the 35th day of life. The T1
      group received standard feed (negative control); T2 was treated with standard
      feed supplemented with 66 ppm of salinomycin (positive control); groups T3 and T4
      had standard feed supplemented with the ethyl acetate fraction from methanolic
      extract of E. alba aerial parts, which contains the coumestans WL and DWL (120
      and 180 ppm, respectively). The chicken broilers were individually infected with
      2 * 104 oocysts of Eimeria tenella when they were 14 days old and were monitored
      weekly to evaluate zootechnical parameters such as weight gain and food
      conversion ratio. Counting of coccidial oocyst in chicken feces was assessed from
      random samples, from the 21st to 28th days of life, which corresponded to 7-14
      days after the infection. Five chickens selected at random from each experimental
      group were subsequently euthanized at 21, 28 or 35 days of life to determine the
      lesion score in the cecal region and to excise a cecum portion for
      histopathological evaluation. The group treated with coumestans from E. alba
      presented an average weight gain and food conversion ratio higher than the
      negative control group and similar to the mean value of the positive control
      group. Coumestan-treated groups showed a significant decrease in the oocyst
      counting since the 21 th day of life and displayed a reduced number of
      macroscopic lesions. Histopathological evaluations of cecum fragments showed that
      both treatments induced the migration of defense cells at the site of infection.
      A severe destruction of the cecal lining was found in the intestinal tract of
      broilers fed with a coumestans dose of 180 ppm. Overall, our results validate the
      use of a phytotherapy containing E. alba coumestans at a dose of 120 ppm as a
      therapeutic or prophylactic agent against avian coccidiosis.

PMID- 21177039
TI  - Limits of the therapeutic properties of synthetic S3Pvac anti-cysticercosis
      vaccine.
AB  - The S3Pvac synthetic vaccine, composed of three peptides (GK1, KETc1 and KETc12)
      effectively protects against cysticercosis under experimental and field
      conditions. Additionally, S3Pvac vaccine can effectively damage early-established
      cysticerci in experimentally lightly infected young pigs. This study was designed
      to explore if also fully-developed cysticerci that eluded immunity induced by the
      infection can be damaged by S3Pvac-induced immunity in naturally, heavily
      infected adult pigs. Fourteen pigs identified as cysticercotic by tongue
      inspection from rural communities were purchased and moved to controlled
      conditions in the Faculty of Veterinary Medicine. Half of these pigs were treated
      once a month three times with S3Pvac plus saponin, and the other half received
      only saponin (controls). Twelve months later pigs were euthanized, and the number
      of cysticerci, their macro and microscopic status and their capacity to transform
      into tapeworms were determined. S3Pvac failed to damage fully-developed muscle
      cysticerci of naturally, heavily infected adult pigs. To explore possible factors
      involved in the failure of the therapeutic capacity pooled sera from control and
      treated cysticercotic pigs were added to mice mononuclear peripheral cells.
      Pooled sera from non-infected pigs were also tested. Sera from control and
      treated infected pigs almost completely suppressed the T cell proliferative
      responses, pointing to the presence of suppressor factors. In conclusion, S3Pvac
      vaccine failed to damage fully-developed cysticerci in pigs in which a host
      parasite relationship had evolved after months of infection with immunological
      implications.

PMID- 21177040
TI  - Discordances in ER, PR and HER2 receptors after neoadjuvant chemotherapy in
      breast cancer.
AB  - Neoadjuvant chemotherapy (NAC) for breast cancer is evolving and subsequent
      adjuvant systemic treatment is mainly based on the presence of the Estrogen (ER)
      receptor, Progesterone (PR) receptor and Human Epidermal growth factor Receptor 2
      (HER2) status on the core needle biopsy prior to treatment. It is not well known
      whether these biomarkers change after NAC, requiring a change in further adjuvant
      systemic treatment. A review of the literature (PubMed search) revealed 32
      relevant studies that investigated the concordance of the hormone receptors (ER
      and/or PR) and HER2 after NAC with or without trastuzumab. Discordance of the
      hormone receptor status was reported in four out of eight studies in 8-33% of the
      patients. About half of the studies that tested the ER and PR receptor status
      separately reported discordances of 2.5-17% and 5.9-51.7% respectively. Studies
      that concluded that ER and/or PR receptor remained stable after NAC were
      performed with evidently lower number of patients compared to studies that
      reported a change. Good concordance of the HER2 amplification tested with FISH
      was reported, although the HER2 expression measured with immunohistochemistry was
      more discordant. A switch to a negative HER2 receptor in up to 43% of the
      patients was reported when NAC was combined with trastuzumab. Until more
      comparable studies are being published, retesting the receptor status of the
      residual tumor after NAC should be considered in order to improve future tailored
      adjuvant therapies.

PMID- 21177041
TI  - Individual and family factors associated with intention to quit among male
      Vietnamese American smokers: implications for intervention development.
AB  - Smoking prevalence among Vietnamese American males remains higher than the U.S.
      general population. This study examined the associations of individual and family
      factors with quit intention among Vietnamese male smokers in California to guide
      intervention development to reduce their smoking prevalence. Data for Vietnamese
      male current smokers (n=234) in the 2008 California Vietnamese Adult Tobacco Use
      Survey (N=1101 males) were analyzed to describe quit intention and previous quit
      attempts. One-third of Vietnamese male smokers (33%) had no intention to quit at
      any time, 36% intended to quit soon (in the next 30 days), and 31% intended to
      quit later (beyond the next 30 days). Half (51.7%) of the sample was in
      "precontemplation," indicating no intention to quit within 6 months. Many (71%)
      had made a serious quit attempt in the past year, but 68% of those who tried to
      quit used no cessation assistance. Multivariate logistic regression adjusting for
      age, depression, smoking intensity, nicotine dependence, health knowledge,
      children in the household and home smoking ban revealed that having smoking
      related family conflicts and a quit attempt in the past year with or without
      assistance were independently associated with an intention to quit either in the
      next 30 days or later. Higher education was associated with no intention to quit.
      Findings underscore the importance of designing strategic interventions that meet
      the needs of smokers at both individual and family levels to promote quit
      intention and to facilitate successful quitting in this population.

PMID- 21177043
TI  - Sleep debt and serotonin. A response to a comment on my hypothesis.

PMID- 21177042
TI  - The false memory syndrome: experimental studies and comparison to confabulations.
AB  - False memories, or recollections that are factually incorrect but strongly
      believed, remain a source of confusion for both psychiatrists and neurologists.
      We propose model for false memories based on recent experimental investigations,
      particularly when analyzed in comparison to confabulations, which are the
      equivalent of false memories from neurological disease. Studies using the
      Deese/Roedinger-McDermott experimental paradigm indicate that false memories are
      associated with the need for complete and integrated memories, self-relevancy,
      imagination and wish fulfillment, familiarity, emotional facilitation,
      suggestibility, and sexual content. In comparison, confabulations are associated
      with the same factors except for emotional facilitation, suggestibility, and
      sexual content. Both false memories and confabulations have an abnormal sense of
      certainty for their recollections, and neuroanatomical findings implicate
      decreased activity in the ventromedial frontal lobe in this certainty. In
      summary, recent studies of false memories in comparison to confabulations support
      a model of false memories as internally-generated but suggestible and emotionally
      facilitated fantasies or impulses, rather than repressed memories of real events.
      Furthermore, like confabulations, in order for false memories to occur there must
      be an attenuation of the normal, nonconscious, right frontal "doubt tag"
      regarding their certainty.

PMID- 21177044
TI  - Evaluation of different starter cultures (Staphylococci plus Lactic Acid
      Bacteria) in semi-ripened Salami stuffed in swine gut.
AB  - The ripening properties were evaluated in semi-ripened pork Salami started by
      different cultures: CXP (Pediococcus pentosaceus, Staphylococcus xylosus and
      Staphylococcus carnosus); RAP (Lactobacillus plantarum, Lactobacillus sakei, S.
      xylosus and S. carnosus); and GY2 (L. sakei, S. xylosus and S. carnosus). These
      starters were chosen by their technological activities: CXP (rapid acidifying);
      RAP (medium acidifying); and GY2 (slow acidifying plus intense reddening
      flavouring). Salami was enhanced with Ponceau 4R red and sodium glutamate,
      stuffed in pig gut and aged for 12 days at 15  degrees C/65-85%RH. Dehydration,
      reddening, proteolysis, fat acidity and lipid oxidation were hardly affected by
      the starters. Acidification by LAB strongly influenced the flavour. L. sakei plus
      L. plantarum provided a better flavouring than a low dose of L. sakei, and,
      especially, than over-acidifying P. pentosaceus. A final pH of 5 seems to be
      suitable for preventing aroma and taste defects in semi-ripened Salami.
      Spontaneous lactic microflora showed great acidifying potential.

PMID- 21177045
TI  - Efficacy and toxicity of chemoradiotherapy using intensity-modulated radiotherapy
      for unknown primary of head and neck.
AB  - PURPOSE: No single standard treatment paradigm is available for head-and-neck
      squamous cell carcinoma of an unknown primary (HNCUP). Bilateral neck
      radiotherapy with mucosal axis irradiation is widely used, with or without
      chemotherapy and/or surgical resection. Intensity-modulated radiotherapy (IMRT)
      is a highly conformal method for delivering radiation that is becoming the
      standard of care and might reduce the long-term treatment-related sequelae. We
      report the Dana-Farber Cancer Institute experience with IMRT-based treatment for
      HNCUP. PATIENTS AND MATERIALS: A retrospective study of all patients treated at
      the Dana-Farber Cancer Institute for HNCUP with IMRT between August 2004 and
      January 2009. The primary endpoint was overall survival; the secondary endpoints
      were locoregional and distant control, and acute and chronic toxicity. RESULTS: A
      total of 24 patients with HNCUP were included. Of these patients, 22 had Stage N2
      disease or greater. All patients underwent neck computed tomography, positron
      emission tomography-computed tomography, and examination under anesthesia with
      directed biopsies. Of the 24 patients, 22 received concurrent chemotherapy, and 7
      (29%) also underwent induction chemotherapy. The median involved nodal dose was
      70 Gy, and the median mucosal dose was 60 Gy. With a median follow-up of 2.1
      years, the 2-year actuarial overall survival and locoregional control rate was
      92% and 100%, respectively. Only 25% of the patients had Grade 2 xerostomia,
      although 11 patients (46%) required esophageal dilation for stricture.
      CONCLUSION: In a single-institution series, IMRT-based chemoradiotherapy for
      HNCUP was associated with superb overall survival and locoregional control. The
      xerostomia rates were promising, but the aggressive therapy was associated with
      significant rates of esophageal stenosis.

PMID- 21177046
TI  - Treatment for hepatitis C virus genotype 1 infection in HIV-infected individuals
      on methadone maintenance therapy.
AB  - BACKGROUND: A minority of HIV/HCV coinfected patients with opiate addiction
      undergo HCV treatment. HCV therapy for HCV-monoinfected methadone maintenance
      (MM) recipients is safe and effective. We evaluated treatment efficacy and
      adherence to pegylated interferon (pegIFN) among HIV/HCV coinfected MM
      recipients. METHODS: HCV treatment-naive, HIV-infected persons 18-65 years with
      chronic HCV genotype 1 on MM were prospectively enrolled in an HCV treatment
      study at two HIV clinics. At weekly visits pegIFN alfa-2a injections were
      directly administered. Daily MM recipients had morning ribavirin delivered with
      methadone at off-site methadone clinics. Weekly take-home MM recipients took
      ribavirin unsupervised. Target enrollment was 30 participants. RESULTS: During 18
      recruitment months, 11 participants were enrolled, 6 of whom received daily
      methadone. Mean age was 46, 64% were female, 5 were Caucasian, 4 Black and 2
      Hispanic. At baseline, 82% had high HCV RNA and 55% had stage 2 fibrosis or
      greater. The majority (91%) were on HAART, and 82% had undetectable HIV RNA with
      a median CD4(+) of 508cells/MUL. All had polysubstance use history, non-substance
      based psychiatric diagnoses and were on psychotropic medications pre-enrollment.
      Two (18%) participants achieved a Sustained Virologic Response (SVR). Two
      completed 48 treatment weeks, 5 were withdrawn due to adverse events, 2 dropped
      out prematurely and 2 had treatment discontinued for virologic non-response. Of
      on-treatment weeks, adherence to pegIFN was >99%. CONCLUSIONS: SVR rate was
      comparable to historic controls for coinfected genotype 1 patients, with optimal
      pegIFN adherence. Adverse effects often prevented therapy completion in this
      population.

PMID- 21177047
TI  - Is there a misplaced focus on AmED? Associations between caffeine mixers and bar
      patron intoxication.
AB  - BACKGROUND: Previous research on alcohol mixed with energy drinks (AmED) suffers
      from measurement problems. Missing from the research literature are studies that
      assess caffeine-alcohol co-ingestion in natural drinking environments. METHODS:
      This field study collected data in a U.S. college bar district from 328 randomly
      selected patrons. Anonymous data were obtained from face-to-face interviews and
      self-administered surveys, and from breath tests. RESULTS: Cola-caffeinated
      alcoholic beverage consumers left bars in a more highly intoxicated state than
      those who consumed alcohol only. There was no significant difference between the
      intoxication level of the AmED group and the cola-caffeinated alcoholic beverage
      group. Results from a multivariate regression model indicated that quantity of
      caffeinated alcoholic beverage consumption had a significant, positive
      association with bar patron intoxication after adjusting for potential
      confounders. CONCLUSIONS: Findings indicate that caffeine may have a dose
      dependent relationship with alcohol intoxication in the bar/nightclub setting. In
      addition, results revealed that cola-caffeinated alcoholic drinks may pose
      similar levels of risk to bar patrons as those associated with AmED beverage
      consumption. Product labeling requirements about alcohol risks may need to be
      extended not only to energy drinks, but to caffeinated soft drinks as well.

PMID- 21177049
TI  - Identification of capacitation associated tyrosine phosphoproteins in buffalo
      (Bubalus bubalis) and cattle spermatozoa.
AB  - At ejaculation mammalian sperm lack fertilizing ability as they are released in a
      functionally immature form. The capacity to fertilize eggs is only acquired after
      they have been educated in the female reproductive tract and this phenomenon is
      termed as capacitation. Sperm capacitation includes a cascade of biochemical
      modifications, including cholesterol efflux, Ca(2+) influx and cAMP/PKA
      dependent/independent protein tyrosine phosphorylation which is specifically
      considered as the biochemical marker for capacitation. The identification of
      tyrosine phosphoproteins shall be useful in delineating their physiological role
      in different events associated with sperm capacitation. The present study was
      conducted to identify the tyrosine phosphoproteins in the capacitated buffalo and
      cattle spermatozoa using 2D immunoblotting and mass spectrometry. Among several
      proteins identified in the buffalo capacitated sperm, serine/threonine-protein
      phosphatase PP1-gamma catalytic subunit, MGC157332 protein, alpha-enolase, 3
      oxoacid CoA transferase 2 and actin-like protein 7A were identified as new
      tyrosine phosphorylation substrates in mammalian spermatozoa. Cattle sperm also
      contain proteins such as serine/threonine-protein phosphatase PP1-alpha catalytic
      subunit and membrane metallo-endopeptidase-like 1 which have not been reported as
      tyrosine phosphorylated in any other species. Though the presence of
      serine/threonine-protein phosphatase PP1-alpha catalytic subunit was demonstrated
      for the first time in mammalian sperm, further studies are required for its
      existence and possible role in different sperm functions.

PMID- 21177048
TI  - Striatal hyposensitivity to delayed rewards among cigarette smokers.
AB  - BACKGROUND: Brain regions that track value (including the ventral striatum)
      respond more during the anticipation of immediate than delayed rewards, even when
      the delayed rewards are larger and equally preferred to the immediate. The
      anticipatory response to immediate vs. delayed rewards has not previously been
      examined in association with cigarette smoking. METHODS: Smokers (n=35) and
      nonsmokers (n=36) performed a modified monetary incentive functional Magnetic
      Resonance Imaging (fMRI) task (Knutson et al., 2000) that included opportunities
      to win either immediate or delayed rewards. The delayed rewards were larger and
      equally preferred to the immediate rewards. RESULTS: Across groups, greater
      activation was observed in regions previously shown to track value including
      bilateral ventral/dorsal striatum during the anticipation of immediate relative
      to delayed rewards. This effect was significantly greater among smokers than
      nonsmokers within the right ventral striatum. This group difference was driven
      particularly by low striatal activation among smokers during delayed reward
      trials. CONCLUSIONS: The general tendency for striatal reward anticipatory
      activity to be attenuated when rewards are delayed is exaggerated among smokers
      relative to comparison participants. Among possible explanations of this
      relationship are that (1) low anticipatory response to delayed rewards is a
      phenotypic risk factor for smoking and (2) smoking-related neuroadaptations
      result in reduced recruitment during the anticipation of delayed rewards.

PMID- 21177050
TI  - The influence of inclusions of vitamin E and corn oil on semen traits of Japanese
      quail (Coturnix coturnix japonica).
AB  - Reported was an investigation of the effect of vitamin E (Vit.E) and corn oil on
      semen traits of male Japanese quail (Coturnix coturnix japonica). From 8 to 20 wk
      of age, birds were raised on corn-based diets supplemented with corn oil (0 and
      3%) and Vit.E (National Research Council (NRC) recommended 25mg/kg/day/dry matter
      and 150 mg/kg/day/dry matter) in a 2*2 factorial manner. The diet was
      supplemented with corn oil and Vit.E (E2C2) which provided additional n-6
      polyunsaturated fatty acids in the form of 20:4n-6 and 22:4n-6 in spermatozoa
      phospholipid. The left testes weights were increased (P<0.01) in groups that
      received Vit.E in the diet (3.95 and 4.12 g, respectively) (P=0.03) and combined
      testes weight was the greatest in E2C2 group (7.57g) (P=0.02). Semen volume
      increased throughout the experiment in the E2C2 group. E2C1 and E2C2 birds had
      the greatest (90.05% and 92.1%, respectively) live sperm percent by comparison
      with other groups. The susceptibility of semen to lipid peroxidation in vitro was
      increased in quail fed E1C1 and E1C2, but was reduced when 150 mg Vit.E
      kg/day/dry matter feed was provided in the diet. The amount of Vit.E in the
      seminal plasma of E1C1 and E1C2 groups was (P<0.01) less than that in the other
      two groups (E2C1 and E2C2). From this study, it may be concluded that increasing
      diet n-6/n-3 ratio can be beneficial for semen traits, however, this application
      increased sperm peroxidation sensitivity but it can be controlled by inclusion of
      antioxidant such as Vit.E (150 mg/kg/day/dry matter) to diet.

PMID- 21177051
TI  - Beneficial effects of testosterone therapy in women measured by the validated
      Menopause Rating Scale (MRS).
AB  - OBJECTIVES: This study was designed to measure the beneficial effects of
      continuous testosterone therapy, delivered by subcutaneous implant, in the relief
      of somatic, psychological and urogenital symptoms in both pre- and post
      menopausal patients, utilizing the validated Health Related Quality of Life
      (HRQOL), Menopause Rating Scale (MRS). STUDY DESIGN: 300 pre- and post-menopausal
      women with symptoms of relative androgen deficiency, were asked to self
      administer the 11-item MRS, at baseline and 3 months after their first insertion
      of the subcutaneous testosterone implant. Baseline hormone measurements,
      menopausal status and BMI, were assessed to determine correlation with symptoms
      and clinical outcome. MAIN OUTCOME MEASUREMENTS: Changes related to therapy were
      determined. Total MRS scores as well as psychological, somatic and urogenital
      subscale scores were compared prior to therapy and following testosterone implant
      therapy. RESULTS: Pre-menopausal and post-menopausal females reported similar
      hormone deficiency symptoms. Both groups demonstrated similar improvement in
      total score, as well as psychological, somatic and urogenital subscale scores
      with testosterone therapy. Better effect was noted in women with more severe
      complaints. Higher doses of testosterone correlated with greater improvement in
      symptoms. CONCLUSION: Continuous testosterone alone, delivered by subcutaneous
      implant, was effective for the relief of hormone deficiency symptoms in both pre-
      and post-menopausal patients. The validated, HRQOL questionnaire, Menopause
      Rating Scale (MRS), proved a valuable tool in the measurement of the beneficial
      effects of testosterone therapy in both cohorts.

PMID- 21177052
TI  - The potential of urinary androstdiene markers to identify 4-androstenediol (4
      ADIOL) administration in athletes.
AB  - Doping control laboratories accredited by the World Anti-Doping Agency (WADA)
      require criteria that allow endogenous steroids to be distinguished from their
      synthetic analogues in urine. Methodology based on "looking outside the metabolic
      box" was used in this study to identify diagnostic urinary markers of 4
      androstenediol (4-ADIOL) administration. Androst-2,4-diene-17-one and androst-3,5
      diene-17-one are proposed to be formed in urine from acid-catalyzed hydrolysis of
      4-ADIOL sulfoconjugate, a major phase II metabolic product of 4-ADIOL. The
      presence of these markers in the routine gas chromatography-mass spectrometry (GC
      MS) steroid screen was suitable to identify samples requiring confirmation by gas
      chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) - to
      measure the carbon isotope ratio (delta(13)C) of the androstdiene markers and
      confirm their likely synthetic origin based on depleted (13)C content.

PMID- 21177053
TI  - The medical contribution to assessing allegations of torture in international
      fact-finding missions.
AB  - International fact-finding missions directed towards the exposure of possible ill
      treatment of persons deprived of their liberty have become increasingly common
      within the framework of international treaties. Such country visits occur with
      the consent and co-operation of government, provide unfettered access to all
      places of detention and allow private interviews with detainees. The Committee
      for the Prevention of Torture of the Council of Europe, the United Nations
      Special Rapporteur on Torture, and the United Nations Subcommittee on Prevention
      of Torture all engage in such missions, and make use of a medical professional as
      part of the investigative team. The medical contribution to fact finding missions
      assessing ill-treatment of detainees includes an assessment of the conditions of
      detention, the regime and the medical services. Custody doctors and their records
      can be a rich source of information about physical ill-treatment. The interview
      and examination of detainees often occurs in circumstances which are far from
      ideal. The safety and wellbeing of the detainees, including protection from
      reprisals, is always paramount. A medical examination may disclose injuries
      corroborative of specific allegations. More often, a medical history of the
      effects of ill treatment and the description of resolved transient injuries
      provides corroboration, and also forms part of assessing the overall credibility
      of the detainee. Equally important is the consistency of the allegation with
      other evidence obtained from a wide variety of sources including the inspection
      of the place of alleged ill-treatment. The evolved working methods draw on the
      basic principles underlying police criminal investigations and crime scene
      examinations as well as forensic medicine. A forensic medical expert can be a
      useful part of the team in such international fact finding missions.

PMID- 21177054
TI  - A novel proteolipid protein 1 gene mutation causing classical type Pelizaeus
      Merzbacher disease.
AB  - Pelizaeus-Merzbacher disease (PMD) is a rare dysmyelinating disorder caused by
      mutations in the proteolipid protein 1 (PLP1) gene. PMD is generally classified
      according to its clinical or pathological features into classical or connatal
      forms. We describe here a 19-year-old male with classical form PMD who presented
      with stridor and nystagmus in early infancy and whose psychomotor development has
      been severely delayed. Brain magnetic resonance imaging revealed white matter
      abnormalities typical of PMD. Direct sequencing of the PLP1 gene identified two
      nucleotide substitutions. One was a C-to-T transition at -31 in the 5'-flanking
      region of exon 1; the other was a novel point mutation, T-to-C transition in exon
      4, which led to substitution of cysteine for arginine at residue 184. Because
      Cys184 forms a disulphide bridge with Cys228, the Cys184Arg mutation probably
      removes the bridge and changes the tertiary structure of PLP protein. A defective
      disulfide bond in PLP protein could be important in the pathogenesis of PMD.

PMID- 21177055
TI  - [Penile Doppler ultrasound: contribution to the management of erectile
      dysfunction].
AB  - Erectile dysfunction (ED) is a common multifactorial disease, in most situations
      arising from an organic or mixed cause. Most cases of ED classified as arterial
      are linked to endothelial dysfunction in relation to the key factors of
      cardiovascular risk. ED is an indicator of vascular health in general. It is also
      a predictor of cardiovascular events, including coronary heart disease. It has
      also been associated with lower peripheral arterial disease and stroke. At the
      present time, penile Doppler ultrasound examination is relatively little used in
      the management of ED, knowledge of the etiologic factors being most often not
      necessary for therapeutic management, but also because of the absence of
      standardization. Nonetheless, recent large-scale studies have shown that the
      vascular nature of ED, based on Doppler parameters recorded after intracavernous
      injection of vasoactive drugs, was also predictive of cardiovascular events and
      cardiovascular mortality, warranting greater interest in this test.

PMID- 21177056
TI  - Interplay between p53-family, their regulators, and PARPs in DNA repair.
AB  - Abnormalities of the p53 tumor suppressor gene are among the most frequent
      molecular events in human neoplasia. p53 is consequently one of the most studied
      proteins, and is the subject of over 55,500 scientific papers. In this review,
      attention is focused on the functions of p53 in DNA repair. We highlight the
      recent progress in the analysis of protein signals to p53, including PARPs, and
      ubiquitination cascade proteins MDM2, CRM1, USP10 and 14-3-3sigma.

PMID- 21177057
TI  - Detection of diethylene glycol adulteration in propylene glycol--method
      validation through a multi-instrument collaborative study.
AB  - Four portable NIR instruments from the same manufacturer that were nominally
      identical were programmed with a PLS model for the detection of diethylene glycol
      (DEG) contamination in propylene glycol (PG)-water mixtures. The model was
      developed on one spectrometer and used on other units after a calibration
      transfer procedure that used piecewise direct standardization. Although
      quantitative results were produced, in practice the instrument interface was
      programmed to report in Pass/Fail mode. The Pass/Fail determinations were made
      within 10s and were based on a threshold that passed a blank sample with 95%
      confidence. The detection limit was then established as the concentration at
      which a sample would fail with 95% confidence. For a 1% DEG threshold one false
      negative (Type II) and eight false positive (Type I) errors were found in over
      500 samples measured. A representative test set produced standard errors of less
      than 2%. Since the range of diethylene glycol for economically motivated
      adulteration (EMA) is expected to be above 1%, the sensitivity of field
      calibrated portable NIR instruments is sufficient to rapidly screen out
      potentially problematic materials. Following method development, the instruments
      were shipped to different sites around the country for a collaborative study with
      a fixed protocol to be carried out by different analysts. NIR spectra of
      replicate sets of calibration transfer, system suitability and test samples were
      all processed with the same chemometric model on multiple instruments to
      determine the overall analytical precision of the method. The combined results
      collected for all participants were statistically analyzed to determine a limit
      of detection (2.0% DEG) and limit of quantitation (6.5%) that can be expected for
      a method distributed to multiple field laboratories.

PMID- 21177059
TI  - Scaly pink plaques on the left foot: tinea incognito.

PMID- 21177058
TI  - 2011 ACCF/AHA/HRS focused update on the management of patients with atrial
      fibrillation (Updating the 2006 Guideline): a report of the American College of
      Cardiology Foundation/American Heart Association Task Force on Practice
      Guidelines.

PMID- 21177060
TI  - Fire-eater's pneumonia: two case reports of accidentally aspirated paraffin oil.
AB  - BACKGROUND: Fire-eater's pneumonia is a chemical pneumonitis that can develop
      after accidental aspiration of liquid hydrocarbon-based fuel during a flame
      blowing or a fire-eating performance. Typical findings of the patient are similar
      with any infectious pneumonia: chest pain, shortness of breath, cough, fever, and
      hemoptysis can be seen. CASE REPORTS: We report two cases of acute paraffin oil
      induced pneumonia due to accidental aspiration during fire-eating performance.
      CONCLUSION: The symptoms and course of respiratory manifestations and the
      treatment strategies of fire-eater's pneumonia are reviewed.

PMID- 21177061
TI  - Use of an administrative data set to determine optimal scheduling of an alcohol
      intervention worker.
AB  - BACKGROUND: Brief alcohol interventions are efficacious in reducing alcohol
      related consequences among emergency department (ED) patients. Use of non
      clinical staff may increase alcohol screening and intervention; however, optimal
      scheduling of an alcohol intervention worker (AIW) is unknown. OBJECTIVES:
      Determine optimal scheduling of an AIW based on peak discharge time of alcohol
      related ED visits. METHODS: Discharge times for consecutive patients with an
      alcohol-related diagnosis were abstracted from an urban ED's administrative data
      set from September 2005 through August 2007. Queuing theory was used to identify
      optimal scheduling. Data for weekends and weekdays were analyzed separately.
      Stationary independent period-by-period analysis was performed for hourly
      periods. An M/M/s queuing model, for Markovian inter-arrival time/Markovian
      service time/and potentially more than one server, was developed for each hour
      assuming: 1) a single unlimited queue; 2) 75% of patients waited no longer than
      30 min for intervention; 3) AIW spent an average 20 min/patient. Estimated
      average utilization/hour was calculated; if utilization/hour exceeded 25%, AIW
      staff was considered necessary. RESULTS: There were 2282 patient visits (mean age
      38 years, range 11-84 years). Weekdays accounted for 45% of visits; weekends 55%.
      On weekdays, one AIW from 6:00 a.m.-9:00 a.m. (max utilization 42%/hour) would
      accommodate 28% of weekday alcohol-related patients. On weekends, 5:00 a.m.-11:00
      a.m. (max utilization 50%), one AIW would cover 54% of all weekend alcohol
      related visits. During other hours the utilization rate falls below 25%/hour.
      CONCLUSIONS: Evaluating 2 years of discharge data revealed that 30 h of dedicated
      AIW time--18 weekend hours (5:00 a.m.-11:00 a.m.), 12 weekday hours (6:00 a.m.
      9:00 a.m.)--would allow maximal patient alcohol screening and intervention with
      minimal additional burden to clinical staff.

PMID- 21177062
TI  - Nurse turnover in substance abuse treatment programs affiliated with the National
      Drug Abuse Treatment Clinical Trials Network.
AB  - Voluntary nurse turnover, which is costly and disrupts patient care, has not been
      studied as an organizational phenomenon within substance abuse treatment
      organizations. In this exploratory study, we examined the frequency and
      correlates of nurse turnover within treatment programs affiliated with the
      National Drug Abuse Treatment Clinical Trials Network. During face-to-face
      interviews conducted in 2005-2006, 215 program administrators reported the number
      of nurses currently employed. Leaders of programs with nursing staff then
      described the number of nurses who had voluntarily quit in the past year, the
      degree to which filling vacant nursing positions was difficult, and the average
      number of days to fill a vacant position. About two thirds of these programs had
      at least one nurse on staff. In programs with nurses, the average rate of
      voluntary turnover was 15.0%. Turnover was significantly lower in hospital-based
      programs and programs offering adolescent treatment but higher in facilities
      offering residential treatment. Most of the administrators indicated that filling
      vacant nurse positions was difficult and took more than 2 months to complete.
      These findings suggest that nurse turnover is a significant issue facing many
      substance abuse treatment facilities. Efforts to improve retention of the
      addiction treatment workforce should be expanded to include nursing
      professionals.

PMID- 21177063
TI  - Drug resistant MCF-7 cells exhibit epithelial-mesenchymal transition gene
      expression pattern.
AB  - PURPOSE: Multidrug resistance is resistance to structurally unrelated anticancer
      agents. Large-scale expression analysis by using high-density oligonucleotide
      microarrays may provide information about new candidate genes contributing to
      MDR. This study demonstrates alterations in expression levels of several genes
      related to epithelial-mesenchymal transition (EMT) in paclitaxel, docetaxel, and
      doxorubicin resistant MCF-7 cells. METHODS: Resistant sublines were developed
      from sensitive cells by selective paclitaxel, docetaxel, and doxorubicin
      applications in dose increments. cDNA microarray analysis was performed for
      sensitive and resistant cells. Genes having statistically significantly altered
      expression levels more than two-folds compared to the sensitive MCF-7 cells were
      considered. Genes encoding the determinants of the EMT were evaluated.
      Immunostaining was performed for relevant protein expressions. RESULTS: Key
      elements of EMT were transcriptionally activated in paclitaxel, docetaxel and
      doxorubicin resistant sublines. One of the upregulated genes was Slug, a
      transcription factor of E-cadherin, occludin repression, and N-cadherin, vimentin
      activation. Decreased estrogen receptor-alpha (ER) levels in cells might have
      stimulated Slug expression. Increased expression levels of TGF-beta receptor2
      (TGFBR2) together with SMAD3 might have stimulated EMT in resistant cells.
      Immunocytochemistry results confirmed loss of ER and E-cadherin, together with
      high vimentin levels. CONCLUSIONS: EMT was induced in multidrug resistant MCF-7
      cells indicating a relationship of this process and drug resistance. However, the
      relationship of each specific component of EMT with drug resistance requires
      further analysis.

PMID- 21177065
TI  - WITHDRAWN: Naringenin, a flavanone alters the tumorigenic features of C6 glioma
      cells.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published,
      http://dx.doi.org/10.1016/j.bionut.2010.06.001. The duplicate article has
      therefore been withdrawn.

PMID- 21177064
TI  - Scintigraphic evaluation of rhBMP-2-biocoated implants reveals no ectopic bone
      formation.
AB  - The main objectives of the study described below were of two-fold nature: (1) to
      examine if rhBMP-2-biocoated implants in a pig model could lead to ectopic bone
      formation and (2) if quantitative and/or qualitative differences could be found
      between adhesively and covalently bonded BMP II using the scintigraphic method.
      In order to examine these central questions, 26 Gottingen minipigs were allocated
      to three groups with a control group (n=7) and two study groups (n=9 each)
      receiving one of three implant types: (a) chromosulfuric acid treated titanium
      surface as control, (b) non-covalently bonded BMP-2, and (c) covalently bonded
      and immobilized rhBMP-2. Each animal received four barbell-shaped implants, one
      in the proximal and distal metaphysis of each femur. The scintigraphic analyses
      were conducted after four, eight, and 12 weeks postoperatively. The visual
      (qualitative) analysis failed to show ectopic bone formation in any of the three
      groups. The statistical analysis of the relative values for bone formation
      yielded no significant differences between the groups, although the limitation in
      the applied methods do not enable one to draw conclusions regarding the
      histomophometric results.

PMID- 21177066
TI  - WITHDRAWN: The role of ascorbic acid transporter in the lens of streptozotocin
      induced diabetic rat.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published,
      http://dx.doi.org/10.1016/j.bionut.2010.09.008. The duplicate article has
      therefore been withdrawn.

PMID- 21177067
TI  - Interaction of clodronate with fibroblast growth factor 2 reduces FGF2-activity
      in endothelial cells.
AB  - Stabilization of fibroblast growth factors from heat denaturation and proteolytic
      digestion by bound heparin and heparan sulphate proteoglycans is known for more
      than 20 years. Furthermore, ATP-binding to FGF2 also leads to stabilization of
      this growth factor as discovered recently. The physiological importance of this
      protection is not yet clear but has become the focal point of interest. In this
      study we used the method of stabilizing FGF2 from proteolytic degradation to
      identify some bisphosphonates, namely clodronate and etidronate, which interact
      with FGF2. These two bisphoshonates protect FGF2 from tryptic digestion in vitro.
      The circular dichroism spectrum of FGF2 incubated with clodronate was
      significantly shifted compared to the spectrum of non-treated FGF2 indicating a
      conformational change of the protein after clodronate-binding. Additionally,
      clodronate and etidronate at low MUM concentrations induce a concentration
      dependent reduction of FGF2-induced cell proliferation of human umbilical vein
      endothelial cells. In contrast, proliferation of these cells after addition of
      clodronate and etidronate without FGF2 was not influenced by these
      bisphosphonates. Furthermore, the intracellular signaling via ERK1/2 and AKT was
      inhibited by clodronate and the tube formation, indicating the beginning process
      of angiogenesis, was reduced. Our results show for the first time that
      bisphosphonates I) interact with FGF2, II) reduce FGF2-activity and III) decrease
      the angiogenic potential of this growth factor.

PMID- 21177068
TI  - Role of sulforaphane in the anti-initiating mechanism of lung carcinogenesis in
      vivo by modulating the metabolic activation and detoxification of benzo(a)pyrene.
AB  - Biomarkers are central to the molecular epidemiology approach. Since scientific
      research progress within this standard, a more complete biological understanding
      of the specific events underlying the multistage carcinogenesis model is
      essential. Hence the present investigation was designed to assess the anti
      initiating potential of Sulforaphane (SFN) against benzo(a)pyrene [B(a)P] induced
      lung carcinogenesis in female Swiss Albino Mice by evaluating the activities of
      xenobiotic markers, and the balance between phase I and phase II carcinogen/drug
      metabolizing enzymes. We sought to institute whether orally administered SFN
      reaches the lung tissue and increases functional capacity of detoxification
      enzymes in this tissue and compare the biochemical changes associated with the
      initiation of cancer. We demonstrated the inhibitory effects of orally
      administered sulforaphane on B[a]P-induced aryl hydrocarbon receptor (AHR)
      activation which subsequently resulted in decreased Phase-I enzyme activities in
      vivo. The study also highlights that treatment with sulforaphane enhanced the
      Nuclear factor erythroid 2-related factor 2 (Nrf2) transcription which reflects
      its nuclear accumulation and DNA binding in mice, together with the induction of
      phase II enzymes as evident from our results. These modulations by sulforaphane
      further result in decreased carcinogen-induced stress. By and large, the results
      suggest an anti-initiating role of sulforaphane in pre- and post-initiation phase
      of experimentally induced lung carcinogenesis in female Swiss albino mice.

PMID- 21177069
TI  - Preparation, therapeutic efficacy and intratumoral localization of targeted
      daunorubicin liposomes conjugating folate-PEG-CHEMS.
AB  - Folate polyethylene glycol-cholesterol hemisuccinate (folate-PEG-CHEMS) is a
      novel folate ligand firstly synthesized by our group and demonstrated good
      stability and potential targeting results on KB cells in vitro. The current study
      further explored endocytosis mechanisms of liposomes via folate receptor on
      L1210JF cells and assessed targeted therapeutic efficacy of folate-PEG-CHEMS
      anchored liposomes loading daunorubicin (F-L-DNR) in vivo. Folate-PEG-CHEMS was
      synthesized by a modified method. The liposome properties, cell cytotoxicity,
      intracellular and intratumoral localization, and therapeutic efficacy on a murine
      tumor model bearing L1210JF cells were evaluated. High encapsulation efficiency
      (95.1%+/-1.5%) and appropriate particle size (76.0+/-35.5nm) and zeta potential (
      12.83+/-1.36mV) were achieved for F-L-DNR. IC(50) of F-L-DNR on L1210JF cells was
      2-3-folds lower than that of non-targeted liposomal daunorubicin (L-DNR).
      Anticancer efficacy on L1210JF tumor model indicated that mice survival time of F
      L-DNR group at doses of 5mg/kg and 10mg/kg was significantly longer than that of
      L-DNR or free DNR. Confocal fluorescence photographs of F-L-DNR indicated
      enhanced endocytosis of liposomes via folate receptor on L1210JF cells, prolonged
      retaining time in tumors and improved drug release in the tumor site at 24h post
      intravenous injection of F-L-DNR. In conclusion, folate-PEG-CHEMS is an effective
      ligand for folate-targeted daunorubicin liposomes to achieve increased drug
      release in tumor and therapeutic efficacy.

PMID- 21177070
TI  - The incremental value of right ventricular indices for predicting response to
      cardiac resynchronization therapy.
AB  - BACKGROUND: Right ventricular (RV) dysfunction in chronic heart failure (HF) is
      associated with poor prognosis. Cardiac resynchronization therapy (CRT) is an
      established method of improving prognosis in HF. However, the majority of known
      indices predictive of response to CRT are based on left ventricular (LV)
      assessment. The authors hypothesized that baseline RV function and tissue Doppler
      derived dyssynchrony may have incremental value over LV dyssynchrony measures for
      predicting CRT response. METHODS: In this retrospective study, echocardiographic
      examinations were performed in 90 patients before pacemaker implantation and up
      to 18 months afterward. CRT results were evaluated using clinical criteria
      (death, hospitalization for decompensation, change in New York Heart Association
      class >=1, and 10% decreases in both peak ventilatory oxygen uptake and 6-min
      walking distance) and reverse remodeling (>15% reduction in LV end-systolic
      volume). RESULTS: Baseline RV dyssynchrony during isovolumic contraction of 26
      msec facilitated the segregation of responders from nonresponders with 85%
      sensitivity and 100% specificity, as well as synchrony in peak deformation of 54
      msec, with 89% sensitivity and 67% specificity. The minor axis of the RV inflow
      tract predicted reverse remodeling after CRT with sensitivity of 73% and
      specificity of 58% with a cutoff value of 35 mm. According to the clinical
      criteria, LV indices (end-diastolic and end-systolic volumes) and
      interventricular delay gave an overall R(2) value of 0.20 (86.2% correctly
      classified patients; area under the curve, 0.80). The addition of RV dyssynchrony
      parameters (measured in peak strain and isovolumic contraction peak velocities)
      significantly increased the power of the model (R(2) = 0.86; 100% of patients
      correctly classified; area under the curve, 1; P for change in R(2) < .0001).
      CONCLUSIONS: The value of baseline RV function analysis is incremental to LV
      indices for the prediction of clinical response to CRT but not reverse
      remodeling. RV synchronous longitudinal deformation and RV dyssynchronous
      isovolumic velocity are independent predictors of clinical response to CRT.

PMID- 21177071
TI  - Fusion of multi-planar images for improved three-dimensional object
      reconstruction.
AB  - Due to the scan time limitation, our MRI studies of the human tongue can acquire
      only a limited number of contiguous two-dimensional (2D) slices to form a
      volumetric data set in a given series. An interpolated three-dimensional (3D)
      reconstruction using images acquired in a single plane presents artifacts. To
      address this issue, we developed a wavelet-based bidirectional linear fusion
      method that uses slices acquired from sagittal and coronal planes to estimate the
      unknown values of the inter-slice voxels. We use an interpolation method to
      estimate the voxel value based on neighboring fiducial voxels in the bounding
      slices. This interpolation is followed by a wavelet fusion to recover image
      details by integrating prominent coefficients from the interpolated images. Our
      method was evaluated using 2D MR images and 3D phantoms. Experiments demonstrated
      that our method reduces interpolation artifacts and greatly improves the 3D
      reconstruction accuracy. The advantage of our method casts new light on MR
      imaging and image processing and permits us to achieve high resolution and short
      acquisition time simultaneously.

PMID- 21177072
TI  - Evaluation of sensitivity of teeth after mandibular fractures.
AB  - The sensitivity of teeth anterior to a fracture between the mental and mandibular
      foramina has been tested and followed up until reinnervation or 3 years has
      passed. This study assessed the reinnervation period, the number of denervated
      teeth, and their clinical importance. Fifty patients and 459 teeth were examined.
      Two hundred and seventy-three teeth were affected and had potentially impaired
      innervation. Tests after injury showed non-responsive teeth in 81% of affected
      teeth. Six weeks after injury, 19% of teeth were reinnervated; by 1 year after
      injury, 92% of initially non-responsive teeth were reinnervated. Most teeth (34%)
      were reinnervated from 6 weeks to 3 months. All 23/186 initially non-responsive,
      unaffected, contralateral corresponding teeth were reinnervated within 6 weeks. A
      year after injury, 95% of incisors, 91% of canines, 94% of premolars, and 82% of
      molars were reinnervated. Three years after injury, 8% of teeth remain
      denervated. During the second and third years, no reinnervation occurred, but
      clinical signs of pulp devitalisation of denervated teeth occurred in 18% or 1%
      of the initially non-responsive affected teeth. The results revealed the
      stability of pulp 1 year after injury. Denervated teeth should not be treated if
      no clinical or radiological signs of devitalisation exist.

PMID- 21177073
TI  - Impact of early statin initiation on secondary prevention in Japanese patients
      with coronary artery disease.
AB  - BACKGROUND: The effect of early statin initiation on secondary prevention remains
      uncertain in unselected Japanese populations with coronary artery disease (CAD).
      METHODS: We investigated the mortality and morbidity in CAD patients according to
      presence or absence of statins within 3 months after the diagnosis of CAD in the
      Shinken Database cohort study. The primary endpoint was all-cause mortality.
      RESULTS: Data were available on 789 Japanese patients with CAD (male 78.8%).
      Among those, 351 patients (44.5%) received a statin. The mean (SD) baseline low
      density lipoprotein (LDL)-cholesterol levels were 113.6 (35.7) mg/dL in the
      statin group and 113.6 (26.4) mg/dL in the non-statin group (p=0.992). Unadjusted
      2-year survival in patients with or without statins was 98.4% and 92.1%,
      respectively (p<0.001). Among a prespecified subgroup of patients undergoing
      percutaneous coronary intervention (PCI) (n=238 with statins and n=183 without
      statins), a consistent effect of statins on 2-year survival was observed (98.5%
      and 90.9%, respectively, p<0.001). However, there was no significant difference
      in 2-year target lesion revascularization-free survival (77.9% in statins versus
      73.7% in non-statins, respectively, p=0.298). The age- and gender-adjusted
      survival in the PCI subgroup was significantly higher in the statin group [hazard
      ratio (HR) 0.29, 95% confidence interval (CI) 0.095-0.913] compared to non
      statin. Multivariate analysis showed statins significantly reduced mortality (HR
      0.27, 95%CI 0.078-0.944), but not revascularization (HR 0.91, 95%CI 0.589-1.406).
      CONCLUSIONS: This study suggested that statin therapy initiated early after the
      diagnosis of CAD can decrease the risk of fatal events in Japanese CAD patients.

PMID- 21177074
TI  - Angiographic late lumen loss at the site of overlap of multiple CypherTM
      sirolimus-eluting stents: ALSOCE study.
AB  - OBJECTIVES: It has been reported that the overlap of sirolimus-eluting stents
      (SESs) is associated with greater in-stent late lumen loss and more angiographic
      restenosis. The purpose of this study was to evaluate whether the site of such
      overlap shows increased or decreased late lumen loss as assessed by quantitative
      coronary angiogram. METHODS AND RESULTS: We compared 7-month angiographic late
      lumen loss at the site of overlap in patients with multiple overlapping stents
      (overlap SES group, n=48) to that in patients with single stents (single SES
      group, n=144). With regard to baseline angiographic characteristics and
      procedural results, there were significant differences between the overlap SES
      group and the single SES group in lesion complexity, lesion length and reference
      diameter, minimal lumen diameter, and mean stent length. In-stent late lumen loss
      at the 7-month follow-up did not differ significantly between the two groups
      (overlap SES 0.25 +/- 0.61 mm vs. single SES 0.10 +/- 0.55 mm, p=0.11).
      Furthermore, the site of overlap in the overlap SES group did not show greater
      late lumen loss compared to the stented area in the single SES group (0.17 +/-
      0.55 mm vs. 0.10 +/- 0.55 mm, p=0.43). The overlap SES group tended to be
      associated with an increase in binary restenosis compared with the single SES
      group (22.8% vs. 12.8%, p=0.08), while this value was 4.2% at the site of
      overlap. There were no significant differences in death, myocardial infarction,
      target lesion revascularization, or stent thrombosis between the two groups. In
      addition, stent length was the most independent factor of late lumen loss in the
      overlap SES group by multivariate logistic analysis, whereas it was not an
      independent factor of late lumen loss of the SES overlap segment. CONCLUSIONS:
      The site of overlap of overlapping SES dose not associate with greater late lumen
      loss or a higher in-stent binary restenosis rate compared to single SES
      implantation. The overlapping of SES by itself did not increase in-stent late
      lumen loss.

PMID- 21177075
TI  - Seizure remission in adults with long-standing intractable epilepsy: an extended
      follow-up.
AB  - Recent studies have provided much needed data on the probability of seizure
      remission among adults with chronic intractable epilepsy treated medically. Here
      we provide an extended follow-up to our earlier study in order to provide a more
      comprehensive picture of long-term prognosis in this patient population during
      medical treatment. The prevalence cohort was followed for two outcomes-complete
      seizure remission for >= 12 months and subsequent seizure relapse among those
      attaining a seizure remission. The study outcomes were estimated using Kaplan
      Meier analysis. We found that the probability of attaining a >= 12 months of
      complete seizure freedom to be approximately 3-4% per year through 8 years of
      follow-up. By year 5 since the start of seizure remission, the cumulative
      probability of seizure relapse was 81%, although only half of the patients with
      seizure relapse went on to experience their previous seizure frequency.

PMID- 21177076
TI  - The effect of co-administration of the NMDA blocker with agonist and antagonist
      of CB1-receptor on penicillin-induced epileptiform activity in rats.
AB  - Although the activation of CB1-receptor by cannabinoids and block of NMDA
      receptors are known to decrease seizure severity in epilepsy models, the
      interaction between these systems remain elusive. Therefore, the present study
      was initiated to evaluate the possible interactions between cannabinoid compounds
      and NMDA receptor antagonist in the penicillin-induced epileptiform activity in
      rat. In the first set of experiments, 30 min after intracortical injection of
      penicillin, five different doses of memantine (3,5-dimethyl-1-adamantanamine
      hydrochloride, 1, 2.5, 5, 10 or 20mg/kg) were administered intraperitoneally
      (i.p.). In the second set of experiments, intracerebroventricular (i.c.v.) AM-251
      [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole
      3-carboxamide], (0.25 MUg) a CB1-receptor antagonist and ACEA (arachidonyl-2
      chloroethylamide), (7.5 MUg) a CB1-receptor agonist, were administered 15 min
      after memantine (i.p.) application. Memantine, NMDA receptor antagonist, at doses
      of 2.5 and 5mg/kg (i.p.) decreased the mean frequency of penicillin-induced
      epileptiform activity with a maximal effect at 5mg/kg. Memantine, at the lowest
      dose (1mg/kg, i.p.) and highest doses (10 and 20mg/kg, i.p.) did not change the
      frequency of epileptiform activity. ACEA, at a dose of 7.5 MUg, also decreased
      the frequency of epileptiform activity, whereas AM-251, at a dose of 0.25 MUg
      increased the frequency by causing status epilepticus-like activity. The best and
      earlier anti-epileptiform effects appeared in both the presence of memantine
      (5mg/kg, i.p.) and ACEA (7.5 MUg, i.c.v.), which was blocked by CB1-receptor
      antagonist, AM-251. The results of the present study provide electrophysiologic
      evidence for an interaction between cannabinoid system and NMDA receptors,
      probably via NMDA-mediated Ca(2+) influx in the penicillin-induced epilepsy.

PMID- 21177077
TI  - Effect of glycerin on drying stresses in human stratum corneum.

PMID- 21177078
TI  - Increasing frequency of class 1 and 2 integrons in multidrug-resistant clones of
      Acinetobacter baumannii reveals the need for continuous molecular surveillance.

PMID- 21177079
TI  - Evaluation of CHROMagarTM KPC for the detection of carbapenemase-producing
      Enterobacteriaceae in rectal surveillance cultures.
AB  - In this study, the performance of the chromogenic medium CHROMagarTM KPC was
      evaluated and was compared with in-house-daily prepared McConkey agar plates
      supplemented with imipenem (1 mg/L) for the detection of carbapenemase-producing
      Enterobacteriaceae. In this surveillance study, rectal swabs were cultured on
      both media and polymerase chain reaction (PCR) for bla(KPC) and bla(VIM) was used
      to confirm the genotype of growing colonies of Enterobacteriaceae. CHROMagar KPC
      was also tested with 17 genotypically characterised carbapenemase-producing and
      non-producing Gram-negative bacteria. It was shown that CHROMagar allows rapid
      detection of carbapenemase-producing Enterobacteriaceae, although bla(KPC)- and
      bla(VIM)-harbouring isolates could not be differentiated by colour or colony
      morphology. The positive and negative predictive values of the tested methods for
      the detection of carbapenemase-producing Enterobacteriaceae were, respectively,
      100% and 98.8% for CHROMagar KPC and 94.7% and 88.6% for imipenem-supplemented
      McConkey agar. CHROMagar KPC medium is a useful screening medium for
      carbapenemase-producing Enterobacteriaceae in stools in settings with a high
      proportion of patients colonised with a variety of carbapenemase-producers.

PMID- 21177080
TI  - Association of collagen with calcium phosphate promoted osteogenic responses of
      osteoblast-like MG63 cells.
AB  - In this investigation, the effects of the association of the collagen (COLL)
      molecules with the calcium phosphate (CaP) film were examined with respect to
      both the physicochemical properties of the CaP films and the osteoblast
      responses, such as the adhesion, proliferation, differentiation, and
      mineralization. The COLL pre-adsorbed CaP film (CaPA) exhibited significant
      changes in the surface morphology compared to the COLL incorporated CaP film
      (CaPC). The adhesions of the osteoblast-like MG63 cells were similar on the CaPC
      or CaPA films. However, the proliferation of the MG63 cells on CaPC was
      comparable to CaP but considerably different than CaPA. The differentiation of
      the MG63 cells was greatly improved on CaPC and CaPA compared to CaP and more
      pronounced on CaPA. The presence of COLL within or on the CaP films significantly
      modulated the expression of the phenotypic genes, including osteopontin (OPN),
      alkaline phosphatase (ALP), and the transforming growth factor-beta (TGF-beta).
      The expression patterns of these genes elucidated that COLL that was present
      within or on the CaP film supported the osteoblast proliferation and
      differentiation. These positive effects were stronger for CaPA than CaPC. The
      bone-like nodules formed on all of the specimens. However, the mineralization of
      CaPC and CaPA was significantly higher than CaP, indicating that the association
      of CaP with COLL promoted the mineral deposition. Therefore, the association of
      the COLL molecules with the CaP film induced positive effects on the
      biomineralization. Overall, the incorporation of COLL efficiently enhanced the
      osteoblast responses of CaP. This system can be utilized in a drug delivery
      system using calcium phosphate. Although the incorporation effects were slightly
      higher for the osteoblast responses of CaPA than CaPC, CaPC can be used when the
      longer drug release times are desirable.

PMID- 21177081
TI  - Voltammetric determination of antibacterial drug gemifloxacin in solubilized
      systems at multi-walled carbon nanotubes modified glassy carbon electrode.
AB  - A sensitive electroanalytical method for determination of gemifloxacin in
      pharmaceutical formulation has been investigated on the basis of the enhanced
      electrochemical response at multi-walled carbon nanotubes modified glassy carbon
      electrode in the presence of CTAB. Solubilized system of different surfactants
      including SDS, Tween-20 and CTAB were taken for the study of electrochemical
      behaviour of gemifloxacin at modified electrode. The reduction peak current
      increases in the presence of CTAB while other surfactants show opposite effect.
      The modified electrode exhibits catalytic activity, high sensitivity, stability
      and is applicable over wide range of concentration for the determination of
      gemifloxacin. The mechanism of electrochemical reduction of gemifloxacin has been
      proposed on the basis of CV, SWV, DPV and coulometeric techniques. The proposed
      squarewave voltammetric method shows linearity over the concentration range 2.47
      15.5 MUg/mL. The achieved limits of detection (LOD) and quantification (LOQ) are
      0.90 ng/mL and 3.0 ng/mL respectively.

PMID- 21177082
TI  - [Galactosemia associated with Rogers syndrome in a 10-month-old infant].
AB  - Galactosemia and congenital Rogers syndrome or thiamine-responsive megaloblastic
      anemia are 2 rare inherited metabolic diseases. The combination of the 2 diseases
      has never been reported in the literature. We describe the case of an infant
      followed for congenital galactosemia since the age of 8 days, with thiamine
      responsive megaloblastic anemia diagnosed at the age of 10 months. Galactosemia's
      symptoms occur in the first 2 weeks of life with severe liver disease. Total
      eviction of the galactose allows complete regression and prevention of early
      symptoms but does not prevent late complications. Rogers syndrome associates
      megaloblastic anemia, deafness, and diabetes mellitus that begin in childhood.
      Supplementation with thiamine allows regression of anemia and prevents the onset
      of diabetes at least until adolescence.

PMID- 21177083
TI  - [Non-invasive prenatal diagnosis of cystic fibrosis].
AB  - Cystic fibrosis (CF) is a frequently fatal autosomal recessive inherited disease
      affecting around one in 3000 newborns in France, the carrier frequency varying
      from one in 20 to one in 40 subjects depending on the geographical area. The
      disease is caused by a chloride channel defect that is attributable to mutations
      in the gene that encodes the CF transmembrane conductance regulator (CFTR).
      Approximately, 1200 different mutations have been discovered. Among them, the
      F508del mutation accounts for 70% of mutated alleles worldwide. Prenatal
      diagnosis (PND) of inherited monogenic disorders such as CF currently relies on
      invasive procedures--amniocentesis, chorionic villus sampling (CVS)--which carry
      a significant risk of miscarriage (from 0.5 to 3%). Several methods have been
      proposed to enrich circulating fetal cells (CFCs) from blood and use them in PND.
      However, up to now, no assay has been shown to be reliable enough for routine
      application in place of the invasive protocols. When combined with laser
      microdissection, isolation by size of epithelial tumor/trophoblastic cells (ISET)
      allows mutation analysis of DNA from single cells demonstrated to be fetal
      (circulating fetal trophoblastic cells [CFTC]) by short tandem repeat (STR)
      genotyping and uncontaminated with maternal DNA. Application of this protocol to
      12 couples at risk of having a child affected by CF has shown, in a blind study,
      that the new method affords a reliable and safe PND of affected fetus, healthy
      carrier or normal non carrier fetus. A following prospective blind study has then
      been performed on 32 couples at risk of having an affected child. For each
      mother, five or 10 CFTCs have been analyzed with an individual genetic diagnosis
      performed per CFTC. Results have been obtained in 240 CFTC showing that seven
      mothers were carrying an affected foetus, with 100% sensitivity and 100%
      specificity. These results open the way to a multicenter clinical validation
      trial and to the potential future application of the ISET non invasive approach
      as a reliable alternative to the invasive PND procedures.

PMID- 21177084
TI  - A pilot study of the multiherb Kampo medicine bakumondoto for cough in patients
      with chronic obstructive pulmonary disease.
AB  - OBJECTIVES: To evaluate the effect of bakumondoto, Kampo medicine, on cough in
      patients with chronic obstructive pulmonary disease (COPD). DESIGN: A 16-week,
      randomized, open-labeled, cross-over design. SETTING: Outpatient clinics at one
      university hospital and two general hospitals in Japan from May 2007 to March
      2009. PARTICIPANTS: Twenty-four elderly patients (14 men and 9 women aged over
      65) with COPD. INTERVENTION: Treatment with or without bakumondoto for 8 weeks in
      a cross-over design. MEASUREMENTS: The primary outcome measurements were the
      frequency and intensity of cough assessed by a visual analogue scale (VAS) and a
      daily cough diary. Secondary outcome measurements were quality of life (QOL)
      assessed using St. George's Respiratory Questionnaire (SGRQ) and lung functions
      measured using spirometry. RESULTS: Treatment with bakumondoto significantly
      improved cough severity during the first treatment period (week 0 vs. week 8,
      p=0.004) and showed a trend to decrease during the second treatment period (week
      8 vs. week 16, p=0.129) assessed by the VAS. Neither QOL nor lung function was
      affected by the treatment with bakumondoto. CONCLUSION: Bakumondoto may be
      effective in suppressing cough in elderly patients with COPD. To further confirm
      the efficacy, a larger and placebo-controlled study with objective cough
      assessment is necessary.

PMID- 21177085
TI  - Indicator ability of biosubstances in monitoring the moderate occupational
      exposure to toxic metals.
AB  - In order to improve the monitoring system, watching influence of toxic metals on
      human health in industrial plants, indicator properties of different
      biosubstances were compared. Four types of samples (whole blood, plasma, urine,
      and hair) from 263 workers of the "Khimprom" chemical plant (Novocheboksarsk,
      Russia) were subjected to multielement analysis by ICP-AES/ICP-MS. 19-25 chemical
      elements, including main toxic metals (Cd, Hg, Pb, etc.) were determined. The
      results were calculated with regard to workers' individual data on occupational
      exposure to chemical elements. Hair was found to be the most sensitive to toxic
      and conditionally toxic trace metals: Pb, Mn, Cr, Be, Ni, while occupational
      contact with macro elements (Na, P), trace metalloids (Si, B) and some other
      metals (Zn) was not reflected in hair. Whole blood relatively weakly indicated a
      moderate occupational level of metals except Pb and Mn, but effectively reflected
      deficiencies of essential elements: I, Cr, and shifts in K/Na ratio, which are
      likely to be secondary effects of harmful occupational factors. Blood plasma
      reflected only contact with Be, P; urine--only with Ni. In both whole blood and
      plasma the changes for the absolute majority of elements were similar. Thus, hair
      analysis is useful for monitoring the occupational exposure to toxic and
      conditionally toxic chemical elements, while a general estimation of occupational
      harmful influence on mineral metabolism requires simultaneous investigation of
      two biosubstances: hair and whole blood, or hair and blood plasma, with whole
      blood being more preferable. Analysis of urine is appropriate for monitoring
      particular chemical elements, e.g. nickel.

PMID- 21177086
TI  - Preconceptional alcoholic intoxication alters the distribution of metals in
      matured rat brain of offspring.
AB  - It is known that alcohol possesses embryotoxic, teratogenic, neurotoxic and other
      effects. Alteration of the trace element and mineral metabolism can be one of the
      triggering mechanisms of metabolic changes during an alcoholic intoxication. The
      aim of the recent study was to compare the profiles of elements in brain
      structures of matured offspring which were born by female rats exposed and non
      exposed to alcohol before conception. A decreasing tendency in the levels of all
      detected macro and trace elements in four brain structures was observed. The most
      prominent changes were found in the brain cortex. Experimental data show that
      short term consumption of alcohol by female rats before pregnancy alters the
      distribution of macro and trace elements in the offspring's brain structures.

PMID- 21177087
TI  - Omega-3 fatty acids modulate collagen signaling in human platelets.
AB  - Dietary intake of the omega-3 fatty acids eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) results in cardioprotective benefits. However, the
      cellular and physiological bases for these benefits remain unclear. We
      hypothesized that EPA and DHA treatments would interfere with collagen-mediated
      platelet signaling. Thirty healthy volunteers received 28 days of 3.4 g/d EPA+DHA
      with and without a single dose of aspirin. Clinical hematologic parameters were
      then measured along with assays of collagen-stimulated platelet activation and
      protein phosphorylation. Omega-3 therapy led to a small but significant reduction
      in platelets (6.3%) and red blood cells (1.7%), but did not impair clinical time
      to-closure assays. However, collagen-mediated platelet signaling events of
      integrin activation, alpha-granule secretion, and phosphatidylserine exposure
      were all reduced by roughly 50% after omega-3 incorporation, and collagen-induced
      tyrosine phosphorylation was significantly impaired. The diminished platelet
      response to collagen may account for some of the cardioprotective benefits
      provided by DHA and EPA.

PMID- 21177088
TI  - Intermittent administration of a sustained-release prostacyclin analog ONO-1301
      ameliorates renal alterations in a rat type 1 diabetes model.
AB  - Diabetic nephropathy is the most common pathological disorder predisposing end
      stage renal disease. ONO-1301 is a novel sustained-release prostacyclin analog
      possessing thromboxane (TX) synthase inhibitory activity. Here, we aimed to
      investigate the therapeutic efficacies of ONO-1301 in a rat type 1 diabetic
      nephropathy model. Streptozotocin (STZ)-induced diabetic rats received injections
      of slow-release form of ONO-1301 (SR-ONO) every 3 weeks. Animals were sacrificed
      at Week 14. SR-ONO significantly suppressed albuminuria, glomerular hypertrophy,
      mesangial matrix accumulation, glomerular accumulation of monocyte/macrophage,
      increase in glomerular levels of pro-fibrotic factor transforming growth factor
      (TGF)-beta1 and the number of glomerular alpha-smooth muscle actin (SMA)(+) cells
      in diabetic animals. The glomerular levels of hepatocyte growth factor (HGF) were
      significantly increased in SR-ONO-treated diabetic animals. Taken together, these
      results suggest the potential therapeutic efficacy of intermittent administration
      of SR-ONO in treating diabetic nephropathy potentially via inducing HGF, thus
      counteracting the pro-fibrotic effects of TGF-beta1.

PMID- 21177090
TI  - Nesprins LINC the nucleus and cytoskeleton.
AB  - Like other spectrin repeat proteins, nesprins co-ordinate and maintain cellular
      architecture by linking membranous organelles to the cytoskeleton. However
      nuclear envelope (NE) nesprins, uniquely hardwire the nuclear lamina to the
      cytoskeleton and molecular motors. Emerging evidence suggests that nesprins also
      form a continuous network linking the plasma membrane to the NE that potentially
      translates mechanical stimuli into nuclear reorganisation. Surprisingly, this
      network is also essential for cytoskeletal organisation and its disruption has
      dramatic effects on nuclear migration, centrosomal positioning, focal adhesion
      maturation and cell motility. Herein we review recent advances in our
      understanding of how nesprins couple to various filamentous systems within the
      cell and emphasise the importance of both KASH and KASH-less nesprin isoforms in
      these interactions.

PMID- 21177089
TI  - Postnatal deficiency of essential fatty acids in mice results in resistance to
      diet-induced obesity and low plasma insulin during adulthood.
AB  - Our objective was to investigate the long-term metabolic effects of postnatal
      essential fatty acid deficiency (EFAD). Mouse dams were fed an EFAD diet or an
      isoenergetic control diet 4 days before delivery and throughout lactation. The
      pups were weaned to standard diet (STD) and were later subdivided into two
      groups: receiving high fat diet (HFD) or STD. Body composition, energy
      expenditure, food intake and leptin levels were analyzed in adult offspring.
      Blood glucose and plasma insulin concentrations were measured before and during a
      glucose tolerance test. EFAD offspring fed STD were leaner with lower plasma
      leptin and insulin concentrations compared to controls. EFAD offspring fed HFD
      were resistant to diet-induced obesity, had higher energy expenditure and lower
      levels of plasma leptin and insulin compared to controls. These results indicate
      that the fatty acid composition during lactation is important for body
      composition and glucose tolerance in the adult offspring.

PMID- 21177091
TI  - Development of nanostructured bioanodes containing dendrimers and dehydrogenases
      enzymes for application in ethanol biofuel cells.
AB  - This paper describes the use of the electrostatic layer-by-layer (LbL) technique
      for the preparation of bioanodes with potential application in ethanol/O(2)
      biofuel cells. More specifically, the LbL technique was employed for
      immobilization of dehydrogenase enzymes and polyamidoamine (PAMAM) dendrimers
      onto carbon paper support. Both mono (anchoring only the enzyme alcohol
      dehydrogenase, ADH) and bi-enzymatic (anchoring both ADH and aldehyde
      dehydrogenase, AldDH) systems were tested. The amount of ADH deposited onto the
      Toray(r) paper was 95 ng cm(-2) per bilayer. Kinetic studies revealed that the
      LbL technique enables better control of enzyme disposition on the bioanode, as
      compared with the results obtained with the bioanodes prepared by the passive
      adsorption technique. The power density values achieved for the mono-enzymatic
      system as a function of the enzyme load ranged from 0.02 to 0.063 mW cm(-2) for
      the bioanode containing 36 ADH bilayers. The bioanodes containing a gas diffusion
      layer (GDL) displayed enhanced performance, but their mechanical stability must
      be improved. The bi-enzymatic system generated a power density of 0.12 mW cm(-2).
      In conclusion, the LbL technique is a very attractive approach for enzyme
      immobilization onto carbon platform, since it enables strict control of enzyme
      disposition on the bioanode surface with very low enzyme consumption.

PMID- 21177092
TI  - Dual-mode probe based on mesoporous silica coated gold nanorods for targeting
      cancer cells.
AB  - A dual-mode imaging probe for targeting cancer cells has been fabricated based on
      mesoporous silica coated gold nanorods (MS-GNRs) for the first time. In this
      probe, fluorescence and surface enhanced Raman scattering (SERS) signals can be
      generated independently by using different excitation wavelengths. To investigate
      the targeting performance of the probe, folic acid (FA) is conjugated on the
      outer surfaces of MS-GNRs as a targeting ligand and HeLa cells were used as model
      cancer cells because they overexpress folate receptors (FRs). The endocytosis
      mechanism was verified by competing experiments with free FA through both
      fluorescence images and SERS mappings. Moreover, the cytotoxicity of the probe
      was remarkably reduced in comparison with the GNRs without the silica shell as
      proved by the results of MTT assay. Compared with traditional imaging probes,
      this new type of nanoprobe has great potential for multiplexed imaging in living
      cells, which can be easily realized by using fluorescence and SERS signals.

PMID- 21177093
TI  - Enzyme integrated silicate-Pt nanoparticle architecture: a versatile biosensing
      platform.
AB  - A novel 3-D nanoarchitectured platform based on Pt nanoparticles (nPts) is
      developed for the sensing of sub-nanomolar levels of hydrogen peroxide and for
      the fabrication of amperometric biosensor for uric acid, cholesterol and glucose.
      The nPts have been immobilized on the thiol functional group containing sol-gel
      silicate 3-D network derived from 3-mercaptopropyltrimethoxysilane (MPTS). The
      nanoparticles on the 3-D architecture have size distribution between 7 and 10nm.
      The nPts on the platform efficiently catalyze the oxidation of H(2)O(2) at the
      potential of +0.45 V in the absence of enzymes and redox mediators. This
      nanoarchitectured platform is highly sensitive and can detect H(2)O(2) at sub
      nanomolar levels (0.1 nM) in neutral solution. The nanoarchitectured platform
      does not suffer from interference due to other common easily oxidizable
      interfering agents. Excellent reproducibility, long-term storage and operational
      stability are observed. This platform is used to determine H(2)O(2) concentration
      in rainwater and for the fabrication of biosensors. Amperometric oxidase-based
      biosensing platforms are developed by integrating the enzymes and nPts with the
      silicate network for the sensing of uric acid cholesterol and glucose. The enzyme
      encapsulated 3-D architecture retains the enzymatic activity and efficiently
      detects enzymatically generated H(2)O(2) without any interference. These
      biosensors are stable and show excellent sensitivity and fast response time. A
      linear response was obtained for a wide concentration range of all analytes. The
      practical utilization of the biosensor for the measurement of uric acid,
      cholesterol and glucose in serum sample is demonstrated. The biological sample
      analysis was validated with clinical laboratory measurements.

PMID- 21177094
TI  - A novel label-free amperometric immunosensor for carcinoembryonic antigen based
      on redox membrane.
AB  - A label-free immunosensor was developed to detect the presence of an antigen.
      This immunosensor was based on the modulation of the electrochemistry of the
      surface bound redox species K(3)Fe(CN)(6) (FC). The model antigen was
      carcinoembryonic antigen (CEA) and the model epitope was the antibody of CEA
      (anti-CEA). Glassy carbon (GC) electrode surfaces were first drop-coated with a
      mixture of FC and chitosan and air-dried. The electrode surface was then covered
      with nafion membrane, which contained gold nanoparticles. After binding with
      polyethyleneimine (PEI), glutaraldehyde (GA) was used to cross-link PEI and anti
      CEA. Binding of CEA to the surface bound epitope resulted in attenuation of the
      FC electrochemistry. Under optimal conditions, the response of the label-free
      immunosensor had a linear range of 0.01-150 ng mL(-1) with a detection limit of 3
      pg mL(-1) (S/N = 3). Its response was better than those of radioimmunoassays,
      enzyme-linked immunosorbent assays, and chemiluminescence assays.

PMID- 21177095
TI  - Design of a sandwich-mode amperometric biosensor for detection of PML/RARalpha
      fusion gene using locked nucleic acids on gold electrode.
AB  - In this study, a novel DNA electrochemical probe (locked nucleic acid, LNA) was
      designed and involved in constructing an electrochemical DNA biosensor for
      detection of promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha)
      fusion gene in acute promyelocytic leukemia for the first time. This biosensor
      was based on a 'sandwich' sensing mode, which involved a pair of LNA probes
      (capture probe immobilized at electrode surface and biotinyl reporter probe as an
      affinity tag for streptavidin-horseradish peroxidase (streptavidin-HRP). Since
      biotin can be connected with streptavidin-HRP, this biosensor offered an
      enzymatically amplified electrochemical current signal for the detection of
      target DNA. In the simple hybridization system, DNA fragment with its
      complementary DNA fragment was evidenced by amperometric detection, with a
      detection limit of 74 fM and a linear response range of 0.1-10 pM for synthetic
      PML/RARalpha fusion gene in acute promyelocytic leukemia (APL). Otherwise, the
      biosensor showed an excellent specificity to distinguish the complementary
      sequence and different mismatch sequences. The new pattern also exhibited high
      sensitivity and selectivity in mixed hybridization system.

PMID- 21177096
TI  - Hollow nitrogen-doped carbon microspheres pyrolyzed from self-polymerized
      dopamine and its application in simultaneous electrochemical determination of
      uric acid, ascorbic acid and dopamine.
AB  - Hollow nitrogen-doped carbon microspheres (HNCMS) as a novel carbon material have
      been prepared and the catalytic activities of HNCMS-modified glassy carbon (GC)
      electrode towards the electro-oxidation of uric acid (UA), ascorbic acid (AA) and
      dopamine (DA) have also been investigated. Comparing with the bare GC and carbon
      nanotubes (CNTs) modified GC (CNTs/GC) electrodes, the HNCMS modified GC
      (HNCMS/GC) electrode has higher catalytic activities towards the oxidation of UA,
      AA and DA. Moreover, the peak separations between AA and DA, and DA and UA at the
      HNCMS/GC electrode are up to 212 and 136 mV, respectively, which are superior to
      those at the CNTs/GC electrode (168 and 114 mV). Thus the simultaneous
      determination of UA, AA and DA was carried out successfully. In the co-existence
      system of UA, AA and DA, the linear response range for UA, AA and DA are 5-30
      MUM, 100-1000 MUM and 3-75 MUM, respectively and the detection limits (S/N = 3)
      are 0.04 MUM, 0.91 MUM and 0.02 MUM, respectively. Meanwhile, the HNCMS/GC
      electrode can be applied to measure uric acid in human urine, and may be useful
      for measuring abnormally high concentration of AA or DA. The attractive features
      of HNCMS provide potential applications in the simultaneous determination of UA,
      AA and DA.

PMID- 21177097
TI  - Simultaneous degradation of refractory contaminants in both the anode and cathode
      chambers of the microbial fuel cell.
AB  - In this study, the microbial fuel cell (MFC) was combined with the Fenton-like
      technology to simultaneously generate electricity and degrade refractory
      contaminants in both anode and cathode chambers. The maximum power density
      achieved was 15.9 W/m(3) at an initial pH of 3.0 in the MFC. In the anode
      chamber, approximately 100% of furfural and 96% COD were removed at the end of a
      cycle. In the cathode chamber, the Fenton-like reaction with FeVO(4) as a
      catalyst enhanced the removal of AO7 and COD. The removal rates of AO7 and COD
      reached 89% and 81%, respectively. The optimal pH value and FeVO(4) dosage toward
      degrading AO7 were about 3.0 and 0.8 g, respectively. Furthermore, a two-way
      catalyst mechanism of FeVO(4) and the contaminant degradation pathway in the MFC
      were explored.

PMID- 21177098
TI  - A critical study of the Miura-Maki integral method for the estimation of the
      kinetic parameters of the distributed activation energy model.
AB  - Using some theoretically simulated data constructed from known sets of the
      activation energy distribution f(E) (assumed to follow the Gaussian distribution
      [Formula in text] where E is the activation energy, E(0) is the mean value of the
      activation energy distribution, and sigma is the standard deviation of the
      activation energy distribution) and the frequency factor k(0), a critical study
      of the use of the Miura-Maki integral method for the estimation of the kinetic
      parameters of the distributed activation energy model has been performed from
      three cases. For all cases, the use of the Miura-Maki integral method leads to
      important errors in the estimation of k(0). There are some differences between
      the assumed and calculated activation energy distributions and the differences
      decrease with increasing the assumed k(0) values (for Case 1), with increasing
      the assumed sigma values (for Case 2), and with decreasing the b values (for Case
      3).

PMID- 21177099
TI  - Microwave-assisted pretreatment of woody biomass with ammonium molybdate
      activated by H2O2.
AB  - Pretreatments for enzymatic saccharification are crucial for the establishment of
      lignocellulosic biorefineries. In this study, we focused on ammonium ions and
      peroxometal complexes as potential delignifying agents. We first examined the
      pretreatment of beech wood with nine different ammonium salts in the presence of
      H(2)O(2). Significant pretreatment effects were found only for ammonium
      molybdate, which is transformed to a peroxometal complex on reacting with
      H(2)O(2). Since microwave sensitizer effects are expected for (peroxo)molybdate,
      beech wood was pretreated using external heating and microwave irradiation. As a
      result, a maximum sugar yield of 59.5% was obtained by microwave irradiation at
      140 degrees C for 30 min, while external heating in an autoclave gave a sugar
      yield of 41.8%. We also found that an ammonium ion is the key counterion
      accelerating the pretreatment with molybdate. These results highlight the
      powerful selective delignifying capability of the H(2)O(2)-activated ammonium
      molybdate system energized by microwave radiation.

PMID- 21177100
TI  - Optimization of Spongiochloris sp. biomass production in the abattoir digestate.
AB  - In the present study, the abattoir digestate was used as a culture medium for
      Spongiochloris sp. growth with added mineral components under optimized
      conditions in batch culture. Firstly, an Hadamard matrix was used to investigate
      the impact of certain influencing factors on the Spongiochloris sp. growth. Then,
      a fractional factorial design 2(7-4) was successfully employed to optimize the
      concentration of different added components to abattoir digestate for increased
      Spongiochloris sp. biomass production. The major influencing factors were
      NaHCO(3) and FeSO(4) at a level of 2000 mg/L and 5mg/L, respectively. A high
      biomass production of 5.29 * 10(6) cell/mL and an important content of
      chlorophyll a of 65.32 mg/L were obtained after 42 days of culture of
      Spongiochloris sp. on the defined abattoir medium at static conditions.

PMID- 21177101
TI  - Catalytic upgrading of oil fractions separated from food waste leachate.
AB  - In this work, catalytic cracking of biomass waste oil fractions separated from
      food waste leachate was performed using microporous catalysts, such as HY, HZSM-5
      and mesoporous Al-MCM-48. The experiments were carried out using pyrolysis gas
      chromatography/mass spectrometry (Py-GC/MS) to allow the direct analysis of the
      pyrolytic products. Most acidic components, especially oleic acid, contained in
      the food waste oil fractions were converted to valuable products, such as
      oxygenates, hydrocarbons and aromatics. High yields of hydrocarbons within the
      gasoline-range were obtained when microporous catalysts were used; whereas, the
      use of Al-MCM-48, which exhibits relatively weak acidity, resulted in high yields
      of oxygenated and diesel-range hydrocarbons. The HZSM-5 catalyst produced a
      higher amount of valuable mono aromatics due to its strong acidity and shape
      selectivity. Especially, the addition of gallium (Ga) to HZSM-5 significantly
      increased the aromatics content.

PMID- 21177102
TI  - Bioconversion of wheat stalk to hydrogen by dark fermentation: effect of
      different mixed microflora on hydrogen yield and cellulose solubilisation.
AB  - This study determined hydrogen production, volatile fatty acids (VFAs) generation
      and cellulose solubilisation from anaerobic dark fermentation of wheat stalk and
      showed the effect of different mixed microflora. The cumulative hydrogen yields
      of anaerobic digested activated sludge (AS)-inoculated and anaerobic digested
      dairy manure (DM)-inoculated system were 23.3 and 37.0 mL/g VS at 204 h,
      respectively. A modified Gompertz equation was able to adequately describe the
      production of hydrogen from the batch fermentation by both mixed microflora.
      During the process, acetate and butyrate accounted for more than 76.1% of total
      VFAs for both fermentations. The extent of cellulose solubilisation approached
      46.6% and 75.2% for AS- and DM-inoculated fermentation, respectively. The X-ray
      diffraction (XRD) showed that the crystallinities of both fermented stalks were
      partly disrupted by the mixed microflora, and DM-inoculated fermentation had more
      disruption than AS-inoculated one.

PMID- 21177103
TI  - Evaluation and elimination of inhibitory effects of salts and heavy metal ions on
      biodegradation of Congo red by Pseudomonas sp. mutant.
AB  - In this study, it was attempted to evaluate the influences and also recommended
      some elimination methods for inhibitory effects offered by salts and heavy metal
      ions. Congo red dye solution treated with mutant Pseudomonas sp. was taken as a
      model system for study. The salts used in this study are NaCl, CaCl(2) and
      MgSO(4). 7H(2)O. Though the growth was inhibited at concentrations above 4 g/l,
      toleration was achieved by acclimatization process. In case of heavy metal ions,
      Cr (VI) showed low inhibition up to 500 mg/l of concentration, compared to Zn
      (II) and Cu (II). It was due to the presence of chromium reductase enzyme which
      was confirmed by SDS-PAGE. Zn (II) and Cu (II) ion inhibitions were eliminated by
      chelation with EDTA. The critical ion concentrations obtained as per Han
      Levenspiel model for Cr (VI), Zn (II) and Cu (II) were 0.8958, 0.3028 and 0.204
      g/l respectively.

PMID- 21177104
TI  - In vitro degradation of fluoranthene by bacteria isolated from petroleum sludge.
AB  - An investigation was carried out for in vitro degradation of fluoranthene by four
      bacterial strains (PSM6, PSM7, PSM10 and PSM11) isolated from the petroleum
      sludge. Although all the strains registered their growth in MSM with 100 ppm
      fluoranthene, PSM11 growth was better than other strains. Growth of bacterial
      strains invariably corresponded to their degradation potential of fluoranthene.
      After 168 h of incubation, 61% fluoranthene was degraded by PSM11, followed by
      PSM10 (48%) and PSM6 (42%) and the least was recorded in PSM7 (41%). Besides, 11%
      loss in fluoranthene was attributed to abiotic factors. Thirty-eight times more
      activity of catechol 2,3-dioxygenase than catechol 1,2-dioxygenase showed that it
      played a significant role in fluoranthene degradation. Molecular weight of
      catechol 2,3-dioxygenase isolated from PSM11 was determined as ~ 136 kDa by size
      exclusion chromatography and 34 kDa on denaturing SDS-PAGE, indicating tetrameric
      nature of the enzyme.

PMID- 21177105
TI  - Novel pyrrolo[2,1-f][1,2,4]triazin-4-amines: Dual inhibitors of EGFR and HER2
      protein tyrosine kinases.
AB  - A novel series of 5-((4-aminopiperidin-1-yl)methyl)-pyrrolo[2,1-f][1,2,4]triazin
      4-amines with small aniline substituents at the C4 position were optimized for
      dual EGFR and HER2 protein tyrosine kinase inhibition. Compound 8l exhibited
      promising oral efficacy in both EGFR and HER2-driven human tumor xenograft
      models.

PMID- 21177107
TI  - Video gait analysis for ambulatory children with cerebral palsy: Why, when, where
      and how!
AB  - PURPOSE: This paper outlines the application of video gait analysis (VGA) for
      children with cerebral palsy (CP) when full instrumented three dimensional gait
      analysis (3DGA) is either not indicated or not available. SCOPE: Gait analysis is
      an important part of the assessment of ambulant children with CP for diagnosing
      gait deviations and for evaluating change. Many regard 3DGA as the most
      informative method of assessing gait, however, it is not always accessible,
      practical, or feasible and the detail obtained is not always indicated. VGA in
      conjunction with other carefully selected outcome measures can provide a
      comprehensive gait assessment in situations where 3DGA is not available or not
      indicated. Indications for VGA use include: documenting change in gait pattern
      over time, frequent monitoring in the rehabilitation phase following treatments
      and interventions (including surgery, spasticity management, serial casting and
      intensive therapy), monitoring orthotic changes, and for very young children and
      those with behavioural/cognitive issues that preclude them from cooperating with
      a 3DGA. Simple and inexpensive VGA systems can be set up in most settings. In an
      effort to make the process more objective and reliable a number of observational
      gait scales have been developed. Of these the Edinburgh Gait Score (EGS) has the
      strongest psychometric properties and is the most comprehensive by including both
      the coronal and the sagittal planes. CONCLUSION: While 3DGA remains an important
      part of complex clinical decision-making, there is also an increasingly important
      role for VGA. Guidelines need to be developed for its use within the field of
      gait analysis.

PMID- 21177106
TI  - Septin structure and function in yeast and beyond.
AB  - Septins are conserved GTP-binding proteins that assemble into hetero-oligomeric
      complexes and higher-order structures such as filaments, rings, hourglasses or
      gauzes. Septins are usually associated with a discrete region of the plasma
      membrane and function as a cell scaffold or diffusion barrier to effect
      cytokinesis, cell polarity, and many other functions. Recent structural studies
      of septin complexes have provided mechanistic insights into septin filament
      assembly, but key questions concerning the assembly, dynamics, and function of
      different septin structures remain to be answered.

PMID- 21177108
TI  - Untangling metabolic and communication networks: interactions of enterics with
      phytobacteria and their implications in produce safety.
AB  - Recent outbreaks of vegetable-borne gastrointestinal illnesses across the globe
      demonstrate that human enteric pathogens can contaminate produce at any stage of
      production. Interactions of enterics with native plant-associated microbiota
      influence the microbiological safety of produce by affecting the attachment,
      persistence and proliferation of human pathogens on plants. Supermarket surveys
      have revealed that bacteria, but not fungi or mechanical damage, promote the
      growth of Salmonella enterica on produce. Field and laboratory studies have
      indicated that some plant pathogenic bacteria and fungi facilitate the entry and
      internalization of human pathogens in plants. Conversely, some phytobacteria,
      including those involved in biocontrol of plant diseases, significantly inhibit
      attachment and plant colonization by non-typhoidal Salmonella and enterovirulent
      Escherichia coli by producing antibiotics or competing for nutrients in the
      phyllosphere. In this review, we attempt to elucidate the mechanisms of
      interactions between human enteric pathogens and plant-associated microbiota, and
      describe how these interactions affect produce safety.

PMID- 21177109
TI  - Brain-derived neurotrophic factor levels influence the balance of migration and
      differentiation of subventricular zone cells, but not guidance to the olfactory
      bulb.
AB  - New progenitor cells in the subventricular zone (SVZ) migrate rostrally and
      differentiate into interneurons in the olfactory bulb (OB) throughout life. Brain
      derived neurotrophic factor (BDNF) may influence the normal progression of this
      migration. In the present study, mouse SVZ explant cultures were used to
      investigate how BDNF modulates the behavior of these migrating progenitors.
      Concentrations of BDNF in the physiological range (e.g. 1ng/mL) stimulated
      migration, whereas doses of 10 ng/mL or higher induced SVZ cell differentiation
      and reduced migration. Pharmacological inhibition of the mitogen-activated
      protein kinase (MAPK) pathway blocked the BDNF-induced differentiation of SVZ
      progenitors, indicating that differentiation of SVZ progenitors in response to
      high-dose BDNF is initiated through MAPK. Physiological concentrations of BDNF,
      like the presence of polysialic acid in the tissue, stimulated migration of cells
      from the explant without affecting the speed at which this occurs. Interestingly,
      in vivo immunohistochemical and molecular analysis showed similar levels of BDNF
      in both the SVZ and OB; that is, there was no positive gradient attracting SVZ
      cells towards the OB. Our data show that SVZ cells respond differently to
      different concentrations of BDNF.

PMID- 21177110
TI  - Clinical and biological significance of nemo-like kinase expression in glioma.
AB  - Nemo-like kinase (NLK) is an evolutionarily conserved serine/threonine kinase
      that suppresses the transcriptional activity of beta-catenin/T-cell factor
      complex through phosphorylation of T-cell factor. Wnt/beta-catenin signaling is
      thought to play a critical role in human carcinogenesis, so it is possible that
      NLK acts as a tumor suppressor by regulating the Wnt/beta-catenin pathway. In the
      present study we investigated NLK expression in human gliomas in order to better
      understand its potential value as a therapeutic target for this disease.
      Specimens from 70 human gliomas were subjected to immunohistochemical and western
      blot analysis. We found that NLK expression was directly but inversely correlated
      with glioma grade. A low NLK expression level was associated with poor patient
      outcome. We also analyzed the effect of overexpression of NLK on cell apoptosis
      using a cell counting kit and western blot analysis. Our results suggest that NLK
      induces apoptosis in glioma cells via activation of caspases. NLK may be a useful
      independent prognostic indicator for glioma. Gene therapeutic approaches aimed at
      upregulating NLK expression could be developed for treatment of glioma.

PMID- 21177111
TI  - Clinical and imaging findings in patients with aggressive spinal hemangioma
      requiring surgical treatment.
AB  - Vertebral hemangiomas (VHs) are frequently asymptomatic lesions found
      incidentally during investigations for other spinal problems. Symptomatic VHs are
      less common, and there are few reports of compressive VHs in the literature. VHs
      with aggressive behavior present with low signal intensity on T1-weighted and
      high signal intensity on T2-weighted MRI. We present a case series of four
      patients with compressive VH, all of whom were neurologically compromised. Each
      of the four patients underwent preoperative arterial embolization followed by
      surgical treatment of their VHs. All patients recovered normal motor function
      after surgery. At follow-up (average 53 months), one patient had a recurrent
      tumor requiring reoperation and radiotherapy. Although it is rare, aggressive VH
      can be a devastating condition. Total surgical resection or subtotal resection
      with radiotherapy may be warranted.

PMID- 21177112
TI  - Rational design and synthesis of potent aminoglycoside antibiotics against
      resistant bacterial strains.
AB  - Based on the structural information of biomacromolecule-aminoglycoside complexes,
      a series of kanamycin B analogues were rationally designed and synthesized. A
      convenient approach to the construction of kanamycin derivatives, in which the
      C4'-position on ring I of neamine moiety was modified, was developed. Most
      synthetic analogues exhibited good to excellent antibiotic activity against some
      typical drug-resistant bacteria. The disclosed results suggested that the C4'
      position of aminoglycosides such as kanamycin may be an ideal site for
      modification to gain new modifying enzyme-resistant aminoglycoside antibiotics.

PMID- 21177113
TI  - Predicting the yield of (177)Lu radionuclide produced by the cyclic irradiation
      technique.
AB  - The feasibility study on the production of (177)Lu radioisotope using a low power
      research reactor has been conducted. A reliable method for predicting the yield
      of (177)Lu produced using the cyclic activation technique based on the Westcott
      formalism has been established. A specific activity of 243.24 mCi/g was obtained
      when a (176)Lu(2)O(3) of natural abundance was irradiated for 4 h and decayed for
      20 h for four cycles at GHARR-1 with a neutron flux of 5.0*10(11) ncm(-2)s(-1).

PMID- 21177114
TI  - European Journal of Cardio-thoracic Surgery/Interactive Cardiovascular and
      Thoracic Surgery--reach out for the next decade!

PMID- 21177115
TI  - Persistent sensitivity disorders at the radial artery and saphenous vein graft
      harvest sites: a neglected side effect of coronary artery bypass grafting
      procedures.
AB  - OBJECTIVE: The use of radial artery conduits in coronary artery bypass grafting
      (CABG) surgery is associated with improved long-term patency and patient survival
      rates as compared with saphenous vein conduits. Despite increasing popularity,
      relative incidence of local harvest-site complications and subjective perception
      of adverse long-term sequelae remain poorly described. METHODS: To allow for
      direct comparison, we investigated a consecutive series of patients in whom both
      the radial artery and the saphenous vein had been harvested for isolated CABG
      during a 36-month period. Patients were identified from a prospective database
      that collects baseline clinical information. The patients' own perceptions were
      assessed by a standardized direct telephone survey regarding any persistent
      functional impairment from their arm and leg operation sites. RESULTS: Out of
      1756 CABG patients during the study period, 168 (10%) were eligible (78% men,
      median age: 60.1 +/- 9.6 years, range: 29.6-82.4 years). Of these, 123 (73%)
      could be contacted and interviewed at a median follow-up time of 2.5 +/- 0.9
      years. Surgical wound complications at harvest sites (arms and legs) had occurred
      in 3% and 12%, respectively, and persistent symptoms (arms and legs) were self
      reported as follows: chronic pain (5% and 8%), numbness (32% and 34%) and
      paresthesia/dysesthesia (14% and 7%). Overall, 39% of the patients reported
      persistent discomfort at the arm and 39% at the leg. Both sites were
      simultaneously affected in 21% (P = n.s., paired testing). Logistic regression
      modeling showed that patients with adverse long-term sequelae were younger (P <
      0.005), had a higher body mass index (P < 0.05) and a lower EuroSCORE (P < 0.001)
      at the time of operation (EuroSCORE, European System for Cardiac Operative Risk
      Evaluation). Perioperative wound complications, however, did not predict
      persistence of symptoms. CONCLUSIONS: Persistent harvest-site discomfort occurs
      with astonishing frequency after CABG surgery and affects arms and legs equally.
      Although usually considered a minor complication, long-term limitation to quality
      of life may be substantial, particularly in younger and relatively healthy
      patients. Thus, harvest-site discomfort clearly belongs to the list of possible
      post-CABG complications of which patients need to be aware.

PMID- 21177116
TI  - Editorial comment on The Papworth bleeding risk score: a stratification scheme
      for identifying cardiac surgery patients at risk of excessive early post
      operative bleeding.

PMID- 21177117
TI  - Mitral valve surgery in octogenarians: should we fight for repair? A survival and
      quality-of-life assessment.
AB  - OBJECTIVE: The aim of the study was to evaluate survival and quality of life
      after mitral surgery in octogenarians. METHODS: From 1987 to 2007, 129 patients
      >= 80 years (median age 82 years; minimum 80 years and maximum 89 years)
      underwent mitral surgery (87.6% myxomatous, 10% rheumatic, and 2.3% ischemic)
      with repair procedure in 75 patients and replacement in 54 patients. In the
      repair and the replacement groups, respectively: Logistic EuroSCORE (European
      System for Cardiac Operative Risk Evaluation) was 5.77 (3.5-63) versus 11.1 (3.5
      93.2); and significative preoperative differences were diabetes mellitus (1.3% vs
      16.7%, p=0.002) and previous cardiac surgery (0% vs 16.7%, p=0.0001). Survival
      and quality of life (walking test) were assessed. RESULTS: In the repair and the
      replacement groups, respectively, hospital mortality (1 month) was 2.7% versus
      18.5% (p=0.004). Early (1-6 months) mortality remained high with 9.6% versus
      13.6% (p=0.55). Late mortality (6 months-7 years) was stable with an annual
      mortality of 8% versus 6% per year (p=0.32). The replacement procedure was the
      only significative predictor of mortality with an odds ratio (OR) of 6.7 (1.1
      38.8 (p=0.04)) for operative mortality. Regarding quality of life, with 41
      months' (1.1-180) (100%) follow-up, 54.2% (65.9%) of repair (replace) patients
      were living in a nursing home and walking distance without aid was more than 500
      m in 67.1% (81.2%) of patients. CONCLUSIONS: For elderly patients, 6-month
      mortality better reflects the burden of mitral surgery than the usual 1-month
      mortality. Even though replacement patients have higher operative estimated risk,
      mitral replacement remains, after adjustment, an independent predictor of higher
      operative mortality. Our results claim for wider use of repair technique in
      mitral surgery for the octogenarians, even if replacement is an acceptable option
      when repair is technically uncertain.

PMID- 21177118
TI  - Significant differences in the material properties between aged human and porcine
      aortic tissues.
AB  - OBJECTIVE: Currently, percutaneous aortic valve (PAV) replacement devices are
      being investigated to treat aortic stenosis in patients deemed to be of too high
      a risk for conventional open-chest surgery. Successful PAV deployment and
      function are heavily reliant on the tissue-stent interaction. Many PAV
      feasibility trials have been conducted with porcine models under the assumption
      that these tissues are similar to human; however, this assumption may not be
      valid. The goal of this study was to characterize and compare the biomechanical
      properties of aged human and porcine aortic tissues. METHODS: The biaxial
      mechanical properties of the left coronary sinus, right coronary sinus, non
      coronary sinus, and ascending aorta of eight aged human (90.1 +/- 6.8 years) and
      10 porcine (6-9 months) hearts were quantified. Tissue structure was analyzed via
      histological techniques. RESULTS: Aged human aortic tissues were significantly
      stiffer than the corresponding porcine tissues in both the circumferential and
      longitudinal directions (p < 0.001). In addition, the nearly linear stress-strain
      behavior of the porcine tissues, compared with the highly nonlinear response of
      the human tissues at a low strain range, suggested structural differences between
      the aortic tissues from these two species. Histological analysis revealed that
      porcine samples were composed of more elastin and less collagen fibers than the
      respective human samples. CONCLUSIONS: Significant material and structural
      differences were observed between the human and porcine tissues, which raise
      questions on the validity of using porcine models to investigate the biomechanics
      involved in PAV intervention.

PMID- 21177119
TI  - Nasopharyngeal cancer (NPC) around the Mediterranean area: standard of care.
AB  - Mediterranean area (MA) represents a zone of intermediate incidence (1-5/100,000)
      for NPC, the highest frequency being observed in North Africa (NA) where it is
      characterized by a bimodal age repartition due to a first adolescence peak. In MA
      and NA, NPC remain diagnosed at advanced stages which impact poorly on overall
      and disease-free survival. It's therapy in MA followed the progresses and
      standardisation of protocols, based on concomitant chemoradiotherapy (CCRT) alone
      or preceded by induction chemotherapy (ICT) in advanced (N2-3, T3-4) stages,
      while localized cases are managed irradiation alone. NPC overall an disease-free
      survival improved, due to the use of combined chemo and radiotherapy.

PMID- 21177121
TI  - Overexpression of CXCL16 promotes a vulnerable plaque phenotype in Apolipoprotein
      E-Knockout Mice.
AB  - BACKGROUND: CXCL16 has been shown to be involved in atherosclerotic lesion
      development, but its role in preexisting lesions is still unclear. This study
      aims to assess the effect of CXCL16 on the stability of preexisting lesions.
      METHODS: We firstly measured plasma CXCL16 level in Apolipoprotein E-Knockout
      (ApoE KO) mice with either high-cholesterol diet (HCD) or normal diet (ND) by
      enzyme-linked immunosorbent assay (ELISA). Then, silastic collars were placed
      around the carotid arteries in HCD-ApoE KO mice to accelerate atherosclerotic
      lesions. Five weeks later, CXCL16 was overexpressed by intravenous injection of
      lentivirus carrying CXCL16 transgene. Two weeks after infection, lesions were
      stained with hematoxylin and eosin (HE) and with oil red O. Biomarkers in the
      lesions, such as MMPs, CCL2, VCAM-1 and TNF-alpha were measured by real-time
      polymerase chain reaction (RT-PCR), which indicate the instability of plaques.
      RESULTS: The level of CXCL16 in plasma was higher in HCD-ApoE KO mice as compared
      to ND-ApoE KO mice. Circulating CXCL16 overexpression does not affect the size of
      preexisting plaques, but it leads to vulnerable plaque morphology and increases
      the expression of markers of plaque destabilization. CONCLUSION: Systemic CXCL16
      becomes much higher in atherosclerosis, and it could be a potential atherogenic
      biomarker. Overexpression of CXCL16 promotes the evolution of preexisting lesions
      to vulnerable plaques in ApoE KO mice.

PMID- 21177120
TI  - Ccl22/MDC, is a prostaglandin dependent pyrogen, acting in the anterior
      hypothalamus to induce hyperthermia via activation of brown adipose tissue.
AB  - CC Chemokine ligand 22 (Ccl22) is a selective, high affinity ligand at the CC
      chemokine receptor 4 (Ccr4). We have identified cDNAs encoding both ligand and
      receptor of the Ccl22-Ccr4 pair in cDNA libraries of the anterior
      hypothalamus/pre-optic area (AH/POA) by PCR. The AH/POA is the key brain region
      where endogenous pyrogens have been shown to act on warm sensitive neurons to
      affect thermogenesis in brown adipose tissue (BAT) and other thermogenically
      responsive tissues. We show that functional Ccr4 receptors are present in the
      AH/POA neurons as injection of Ccl22 into the POA but not to other hypothalamic
      nuclei induces an increase in core body temperature as measured by
      radiotelemetry. Indomethacin (5 mg/kg s.c) pre-treatment markedly reduced the
      hyperthermia evoked by POA injection of Ccl22 (10 ng/0.5 ul) and thus suggests
      that this hyperthermia is mediated through cyclooxygenase activation and thus
      likely through the formation and action of the pyrogen prostaglandin E2. The
      temperature elevation involves a decrease in the respiratory exchange ratio and
      increased activation of the brown adipose tissue as demonstrated by 18F-FDG-PET
      imaging. We describe a novel role to the ligand Ccl22 and its receptor Ccr4 in
      the anterior hypothalamus in temperature regulation that depends on the synthesis
      of the endogenous pyrogen, prostaglandin E2.

PMID- 21177122
TI  - Applying an expanded social determinant approach to the concept of adherence to
      treatment: the case of Colombian women living with HIV/AIDS.
AB  - BACKGROUND: The purpose of this study was to explore and analyze social
      determinants that influence adherence among Colombian women living with HIV/AIDS
      in poverty conditions. METHODS: A qualitative, descriptive-interpretative study
      was developed. Forty-seven women participated in five focus group discussions.
      Also, in-depth interviews with six women were conducted. FINDINGS: Results showed
      that women with lower adherence sell their antiretroviral medication to satisfy
      economic needs, and prioritize the care of their HIV-positive children over their
      own adherence needs. In contrast, women with higher adherence were found to
      participate in social support groups offered by nongovernmental organizations.
      CONCLUSION: These findings underscore the need to understand the social
      determinants that facilitate and/or hinder adherence among women in poverty
      associated conditions. Results indicate the need to facilitate access to
      treatment on a timely and continual basis; provide economic resources, including
      support to meet basic needs as well as subsidies for transportation to health
      care centers; and explore mechanism for supporting the care of their offspring.

PMID- 21177124
TI  - Natural suggestibility in children.

PMID- 21177123
TI  - Adolescent pregnancy desire and pregnancy incidence.
AB  - BACKGROUND: Research has suggested the importance of pregnancy desire in
      explaining pregnancy risk behavior among adolescent females. Much of the
      literature, however, uses cross-sectional study designs to examine this
      relationship. Because bias may strongly influence these results, more prospective
      studies are needed to confirm the relationship between pregnancy desire and
      pregnancy incidence over time. METHODS: Nonpregnant adolescents aged 14- to 19
      years (n = 208) completed baseline interviews and interviews every 6 months
      thereafter for 18 months. Logistic regression was used to examine demographic and
      psychosocial correlates of pregnancy desire. Cox regression analysis was used to
      determine whether pregnancy desire predicted pregnancy incidence over time after
      controlling for potential confounders. RESULTS: Twenty-four percent of
      participants either desired pregnancy or were ambivalent toward pregnancy in the
      next year. Pregnancy desire was associated with older age, relationship duration
      of <6 months, and greater perceived stress. After accounting for potential
      confounders, pregnancy desire doubled the risk of becoming pregnant over the 18
      month follow-up period (relative risk, 2.00; 95% confidence interval [CI], 0.99
      4.02). Additionally, a heightened risk for pregnancy was found among those who
      expressed some desire for pregnancy and who were not in school compared with
      those who expressed no desire for pregnancy and who were in school (relative
      risk, 4.84; 95% CI, 1.21-19.31). CONCLUSION: Our analysis reinforces the
      importance of evaluating pregnancy desire among sexually active adolescent
      females. Interventions should target young women in new romantic relationships
      and who are not in school to improve pregnancy prevention efforts. Additionally,
      improving coping abilities may help to reduce feelings of pregnancy desire among
      adolescent females.

PMID- 21177125
TI  - Compliance with screening guidelines for diabetic retinopathy in a large academic
      children's hospital in the Bronx.
AB  - OBJECTIVE: As the rate of type 2 diabetes mellitus (DM) in children is
      increasing, the number of children with complications of DM, such as retinopathy,
      will also increase. American Diabetes Association and American Academy of
      Pediatrics guidelines recommend annual eye exams for children with type 1 DM who
      are older than 10 years, starting 3-5 years after diagnosis. Adolescents with
      type 2 DM should have an exam when diagnosed. This study was designed to
      determine if these guidelines are followed and to determine factors that
      influence providers to follow them. PATIENTS AND METHODS: We identified all 15-
      to 20-year-old patients seen in a pediatric diabetes clinic over 6 months. All
      patients with type 2 DM and those with type 1 DM diagnosed at least 5 years prior
      were included. Charts were reviewed for 18 months to determine whether patients
      were referred for an eye exam. Data extracted included demographics, DM type, DM
      duration, hemoglobin A(1C), and presence of microalbuminuria. RESULTS: Of 80
      patients, 28 (35%) were referred for an eye exam. Patients with a longer duration
      of DM (P=.006) and those with microalbuminuria (P=.02) were more likely to be
      referred for screening. CONCLUSIONS: As only 35% of the patients in this study
      were referred for eye exams, patients at risk for retinopathy are missing
      opportunities for screening and early treatment. With the increasing number of
      children with type 2 DM, more patients will be at risk for retinopathy and its
      consequences. Pediatricians and endocrinologists should be educated about
      referring for annual eye exams.

PMID- 21177126
TI  - Canine bronchomalacia: a clinicopathological study of 18 cases diagnosed by
      endoscopy.
AB  - Canine bronchomalacia (BM) is characterized by weakness leading to collapse of
      the bronchial wall. A prospective study of 18 affected dogs (age range: 1-15
      years) was undertaken to characterize the clinicopathological and histological
      features of BM. Poodles and Yorkshire terriers were commonly affected. Half of
      the dogs were overweight or obese. The clinical presentation was a mild,
      wheezing, chronic cough and pulmonary crackles were heard in 28% of the dogs.
      Compatible radiographic changes were present in 61% of the dogs. Using
      bronchoscopy, both lungs were affected in half of the animals, whereas in the
      others the disease appeared to affect predominantly the left lung. Analysis of
      bronchoalveolar lavage fluid and biopsies of bronchial mucosa revealed pure or
      mixed neutrophilic inflammation. Underlying infectious bronchitis was considered
      possible in 56% of the dogs. It was concluded that canine BM may present as an
      isolated clinical entity associated with infection and/or inflammation.

PMID- 21177128
TI  - Headache in children and adolescents aged 6-18 years in northern Italy:
      prevalence and risk factors.
AB  - OBJECTIVE: Aim of this study is to examine the epidemiology of paediatric
      headache and periodic syndromes in a school population and to evaluate the co
      existence of environmental predisposing conditions. DESIGN AND METHODS: A 60-item
      questionnaire was completed by a school-based sample (n = 1536, ages 6-18 years).
      Diagnostic assessment of primary headache and periodic syndromes was established
      in first section; predisposing conditions in the second section; while the third
      section quantified the frequency of self medication and identified drugs most
      frequently used. RESULTS: Headache was reported by 62.1% of subjects.
      Socioeconomic status, composition of family unit and nutrition habits in the
      first year of life did not appear significantly different in subjects with
      headache compared to healthy controls. A good sleep quality was found in 95.2% of
      healthy controls, in 89.4% of children with occasional headache. Recurrent
      abdominal pain, motor weakness and car sickness was significantly higher in
      primary headache group compared to occasional headache. Depressive/anxious traits
      were significantly higher in primary headache and occasional headache groups than
      in healthy controls. The frequency of aggressive traits was also higher in
      children with primary headache compared to occasional headache and healthy
      control subjects. 72.5% of subjects with primary headache and 58.4% of children
      with occasional headache assumed medicines to relieve pain. Paracetamol was the
      most frequently assumed drug. CONCLUSIONS: Our data show a more frequent
      occurrence of anxious/depressive profile in children suffering from primary
      headache. In agreement with literature data, this research points out that self
      treatment is a relevant problem in paediatric headache.

PMID- 21177127
TI  - Strains of Staphylococcus aureus and pathology associated with chronic
      suppurative mastitis in rabbits.
AB  - Staphylococcal mastitis is one of the main reasons for culling adult does from
      commercial rabbitries. The aim of this study was describe the spectrum of gross
      and microscopic lesions in 178 cases of chronic staphylococcal mastitis in adult
      does and to determine whether there is a correlation between Staphylococcus
      aureus genotypes and pathology. On the basis of histopathology, chronic mastitis
      was differentiated into abscesses (66.3%), suppurative mastitis with a lobular
      pattern (7.9%), cellulitis (19.6%) and mixed lesions (6.2%). Pathological
      presentations were not related to S. aureus genotype.

PMID- 21177129
TI  - Pain perceived in a national community sample of German children and adolescents.
AB  - BACKGROUND: Pain among children is common, yet far less studied compared to that
      among adults. Little has been reported regarding various types of pain in a
      national community sample of German children. METHODS: We examined pain
      experienced within a 3 month timeframe among 14,836 children and adolescents aged
      3-17 years old, who participated in the German Health Interview and Examination
      Survey for Children and Adolescents (KiGGS) 2003-2006. RESULTS: The 3-month
      prevalence rate was 71% for any pain, 47% for recurrent pain, 55% for pain at
      multiple (>=2) locations and 27% for recurrent pain at multiple locations.
      Headache and abdominal pain were the most frequently reported (44.2%, 40.8%)
      either as recurrent (22.8%, 20.3%) or as the most bothersome pain (MBP) (19.6%,
      14.7%). Children from immigrant vs. non-immigrant families and children from
      lower vs. upper social-class families showed significantly higher prevalence
      rates for tooth (14% vs. 10%), lower abdomen (10% vs. 7%), chest (9% vs. 7%), arm
      (9% vs. 6%) and eye pain (9% vs. 5%). Of children with repeated MBP, only 10% of
      them used medications or consulted a doctor about the pain 'often/always,' while
      the majority of them did not act at all. In general, older age groups, females,
      poor health status and urban residence were associated with pain in children.
      CONCLUSIONS: The rather high pain prevalence suggests pain among children may be
      a potential public health issue. Further studies are required to investigate the
      characteristics and correlational attributes of children suffering most
      frequently from pain and children from families with low socioeconomic status.

PMID- 21177130
TI  - Noise reduction by dynamic signal preemphasis.
AB  - In this work we propose an approach to reduce the digitization noise for a given
      dynamic range, i.e., the number of bits, of an analog to digital converter used
      in an NMR receiver. In this approach, the receiver gain is dynamically increased
      so that the free induction decay is recorded in such an emphasized way that the
      decaying signal is digitized using as many number of bits as possible, and at the
      stage of data processing, the original signal profile is restored by applying the
      apodization that compensates the effect of the preemphasis. This approach, which
      we call APodization after Receiver gain InCrement during Ongoing sequence with
      Time (APRICOT), is performed in a solid-state system containing a pair of (13)C
      spins, one of which is fully isotopically labeled and the other is naturally
      abundant. It is demonstrated that the exceedingly smaller peak buried in the
      digitization noise in the conventional approach can be revealed by employing
      APRICOT.

PMID- 21177131
TI  - Regional distribution and ontogeny of the first exon variants of the rat growth
      hormone receptor mRNA in the brain and the pituitary gland.
AB  - Expression of the first exon variants of the rat growth hormone receptor mRNA was
      studied in the brain and the pituitary gland. Four of the five different variant
      mRNA previously identified in the liver were detected in the cerebral cortex by a
      conventional reverse-transcription polymerase chain reaction, and, unlike the
      data reported previously, a quantitative analysis revealed that approximately 90%
      of the total growth hormone receptor mRNA in the cerebral cortex is V1 form. The
      present results suggest that the V1 was also a dominant transcript in other brain
      areas and the pituitary gland, not only in adult but also in fetal and postnatal
      period. The growth hormone receptor expression in the brain was lower during
      fetal period than in adults, while in the pituitary gland, the expression is
      markedly higher in fetuses, suggesting a yet unknown role of growth hormone in
      the development of this organ.

PMID- 21177132
TI  - Mycoplasma felis-associated meningoencephalomyelitis in a cat.
AB  - Mycoplasmas are frequently isolated from many animal species. In domestic cats,
      mycoplasmas may be isolated from respiratory and ocular mucosae, but other sites
      are also occasionally colonized by these organisms. No cases of Mycoplasma
      species-associated neurologic disease have been reported in cats. We describe a
      case of Mycoplasma felis-associated meningoencephalitis in a 10-month-old
      domestic shorthair cat.

PMID- 21177133
TI  - A comprehensive review of Vibrio vulnificus: an important cause of severe sepsis
      and skin and soft-tissue infection.
AB  - Vibrio vulnificus is a halophilic Gram-negative bacillus found worldwide in warm
      coastal waters. The pathogen has the ability to cause primary sepsis in certain
      high-risk populations, including patients with chronic liver disease,
      immunodeficiency, iron storage disorders, end-stage renal disease, and diabetes
      mellitus. Most reported cases of primary sepsis in the USA are associated with
      the ingestion of raw or undercooked oysters harvested from the Gulf Coast. The
      mortality rate for patients with severe sepsis is high, exceeding 50% in most
      reported series. Other clinical presentations include wound infection and
      gastroenteritis. Mild to moderate wound infection and gastroenteritis may occur
      in patients without obvious risk factors. Severe wound infection is often
      characterized by necrotizing skin and soft-tissue infection, including fasciitis
      and gangrene. V. vulnificus possesses several virulence factors, including the
      ability to evade destruction by stomach acid, capsular polysaccharide,
      lipopolysaccharide, cytotoxins, pili, and flagellum. The preferred antimicrobial
      therapy is doxycycline in combination with ceftazidime and surgery for
      necrotizing soft-tissue infection.

PMID- 21177134
TI  - Sonocatalytic performance of Tb7O12/TiO2 composite under ultrasonic irradiation.
AB  - A Tb(7)O(12)/TiO(2) composite was successfully synthesized through a hydrolysis
      calcination process. The Tb(7)O(12)/TiO(2) composite catalyst was characterized
      by scanning electron microscopy (SEM), energy dispersive spectroscopy, UV-Vis
      absorption/reflection spectroscopy, and X-ray diffraction (XRD). The
      heterogeneous sonocatalytic oxidation of amaranth in water, containing dispersed
      pure TiO(2) and Tb(7)O(12)/TiO(2) composite, was investigated under ultrasonic
      irradiation. The activity of the Tb(7)O(12)/TiO(2) catalyst is higher than that
      of pure TiO(2) during the sonodegradation of amaranth. The enhanced sonocatalytic
      activity of the composite may be attributed to the increase in charge separation
      efficiency and the presence of surface acidity.

PMID- 21177135
TI  - Rigid and flexible spinal stabilization devices: a biomechanical comparison.
AB  - The surgical devices for the treatment of degenerative disc disease are based on
      different concepts (rods for spine fusion, ROM-restricting or load-bearing
      devices for dynamic stabilization). In the present work, the effects of some
      stabilization systems on the biomechanics of the lumbar spine were investigated
      by means of a finite element model of the L2-L5 spine segment. Pedicular screws
      and stabilization devices were added at L4-L5. Different rods were considered:
      stainless steel, titanium, PEEK and the composite ostaPek. Two pedicular devices
      aimed at motion preservation were also considered: the FlexPLUS and the DSS. All
      models were loaded by using the hybrid protocol in flexion, extension, lateral
      bending and axial rotation. The spine biomechanics after implantation resulted
      significantly sensitive to the design and the materials of the device. The impact
      of all rods in reducing the ROM was found to be critical (>70% in flexion and
      extension). The dynamic devices were able to preserve the motion of the segment,
      but with different performances (ROM reduction from 30% (DSS) to 50% (FlexPLUS)).
      The shared load was more sensitive to the elastic modulus of the device material
      than the calculated ROMs (from 7% (PEEK) to 48% (stainless steel)). Regarding
      devices aimed at motion preservation, the authors suggest to distinguish
      "flexible" devices, which are able to preserve only a minor fraction (e.g. at
      most 50%) of the physiological ROM, from "dynamic" devices, which induce a
      smaller ROM restriction. However, the optimal characteristics of a stabilization
      device for the treatment of degenerative disc disease still need to be determined
      by means of basic science and clinical studies.

PMID- 21177137
TI  - Cabbage family affairs: the evolutionary history of Brassicaceae.
AB  - Life without the mustard family (Brassicaceae) would be a world without many crop
      species and the model organism Arabidopsis (Arabidopsis thaliana) that has
      revolutionized our knowledge in almost every field of modern plant biology.
      Despite this importance, research breakthroughs in understanding family-wide
      evolutionary patterns and processes within this flowering plant family were not
      achieved until the past few years. In this review, we examine recent outcomes
      from diverse botanical disciplines (taxonomy, systematics, genomics, paleobotany
      and other fields) to synthesize for the first time a holistic view on the
      evolutionary history of the mustard family.

PMID- 21177136
TI  - Neighbourhood deprivation and regional inequalities in self-reported health among
      Canadians: are we equally at risk?
AB  - Individual-level data from the Canadian Community Health Survey was combined with
      area-level data from the 2001 Canada Census to explore the relationship between
      neighbourhood deprivation and regional inequalities in self-reported health
      (n=120,290). While neighbourhood deprivation was a significant predictor of
      fair/poor health in all geographic regions (OR=1.11; 95% CI: 1.08, 1.14), living
      on the Atlantic and Pacific coasts exacerbated the detrimental effects of
      neighbourhood deprivation on the perceived health of respondents (OR=1.21; 1.28).
      By failing to explore regional variations in risk, we could fail to identify
      areas where provincial policies may interact with neighbourhood factors to
      reinforce health inequalities amongst deprived communities.

PMID- 21177138
TI  - Spectroscopic investigation on protein damage by ciprofloxacin under ultrasonic
      irradiation.
AB  - In recent years, sonodynamic activities of many drugs have attracted more and
      more attention of researchers. The correlative study will promote the development
      of sonodynamic therapy (SDT) in anti-tumor treatment. In this work, bovine serum
      albumin (BSA) was used as a protein model to investigate the intensifying effects
      of ciprofloxacin (CPFX) ultrasonically induced protein damage by UV-vis and
      fluorescence spectra. Meanwhile, the conformation of BSA is changed upon the
      addition of CPFX and metal ions under ultrasound (US) so that the damaging site
      of BSA is considered. Various influencing factors, such as US irradiation time,
      metal ions, solution temperature and ionic strength, on the ultrasonically
      induced BSA damage are discussed. It was showed that CPFX could enhance
      ultrasonically induced BSA damage. The damage degree of BSA was aggravated with
      the increasing of US irradiation time, solution temperature, ionic strength as
      well as the addition of metal ions. Furthermore, the reactive oxygen species
      (ROS) in reaction system were detected by oxidation-extraction photometry (OEP).
      Experimental results also showed that US could activate CPFX to produce ROS,
      which were mainly determined as superoxide radical anion (.O2-) and hydroxyl
      radical (.OH).

PMID- 21177139
TI  - 'One-pot' ultrasound irradiation promoted synthesis and spectral characterization
      of an array of novel 1,1'-(5,5'-(1,4-phenylene)bis(3-aryl-1H-pyrazole-5,1(4H,5H)
      diyl))diethanones, a bis acetylated pyrazoles derivatives.
AB  - An array of novel 1,1'-(5,5'-(1,4-phenylene)bis(3-aryl-1H-pyrazole-5,1(4H,5H)
      diyl))diethanones, a bis acetylated pyrazoles derivatives are synthesized in 'one
      pot' by ultrasound irradiation method and are characterized by melting point,
      elemental analysis, MS, FT-IR, one-dimensional NMR (1H and 13C) and two
      dimensional NOESY spectra. The methylene and methane protons of pyrazoles moiety
      splits signal as ABX pattern in the proton NMR spectra and the key nOe
      correlations are confirmed by NOESY spectrum.

PMID- 21177140
TI  - Fluorescence properties of 2-aryl substituted indoles.
AB  - The fluorescence properties of 2-phenylindole, 2-naphthylindole and 2
      anthracenylindole were investigated. 2-Anthracenylindole was newly synthesized by
      Suzuki-Miyaura's coupling. The fluorescence quantum yield of 2-phenylindole was
      the highest and the fluorescence emission maximum wavelength of 2
      anthracenylindole was the longest. The ab initio quantum chemical calculation of
      the 2-anthracenylindole showed that the HOMO and LUMO of 2-anthracenylindole were
      localized in the anthracene moiety.

PMID- 21177141
TI  - The effect of inertial loading on wrist kinetic tremor and rhythmic muscle
      activity in individuals with essential tremor.
AB  - OBJECTIVES: Determine the effect of concentric and eccentric movement and
      contraction intensity on the strength of rhythmic muscle activity in individuals
      with essential tremor (ET). METHODS: 21 ET subjects and 22 healthy controls
      produced wrist flexion-extension movements while supporting sub-maximal loads (no
      load, 5%, 15% and 25% 1-repetition maximum). Kinetic tremor and wrist extensor
      neuromuscular activity were recorded using an angular displacement sensor and
      electromyography (EMG). RESULTS: Rhythmic muscle activity was twice as big during
      movement compared to previous results involving postural or isometric tasks. ET
      subjects with greater rhythmic muscle activity had (1) larger overall kinetic
      tremor amplitude, (2) greater tremor spectral power during eccentric compared to
      concentric movement and (3) a reduction in overall kinetic tremor amplitude and
      the percentage of EMG spectral power accounted for by the tremor spectral peak in
      the presence of inertial loading. CONCLUSIONS: Greater than normal kinetic tremor
      amplitude appears to be limited to ET subjects with higher levels of rhythmic
      muscle activity. Furthermore, rhythmic muscle activity is much greater during
      movement compared to during postural or closed-kinetic tasks. SIGNIFICANCE: The
      strength of rhythmic muscle activity in ET is influenced by the type of
      contraction (i.e., static vs. dynamic) being performed. Clinicians and
      researchers should include measures of simple kinetic tremor as part of their
      assessments.

PMID- 21177142
TI  - An exploratory study of role transition from student to registered nurse
      (general, mental health and intellectual disability) in Ireland.
AB  - Ireland has seen much change in nurse education resulting in four year degree
      programmes since 2002. A unique aspect of these programmes was the incorporation
      of rostered internship. This study explored role transition for a cohort of
      students at pre and post-registration. The sample consisted of fourth year
      students registered on BSc nursing programmes (general, mental health and
      intellectual disability) within an Irish university. The samples were surveyed to
      compare their perceptions and expectations of role transition pre and post
      registration. Data were analysed using SPSS (version 16). Respondents had high
      levels of confidence in clinical abilities both at pre-registration and post
      registration. They also perceived themselves to be competent across a range of
      domains: managing workload, prioritising care delivery, interpersonal skills,
      time management and multidisciplinary team working. However, this research
      highlights pre-registration stress, the need for ongoing feedback and support and
      differences between expected and actual levels of direct patient care
      involvement. It is argued that the rostered internship provided students with a
      valuable opportunity for adjustment and preparation for their role as registered
      nurse. Recommendations include stress management, a supportive environment and
      post-registration preceptorship programmes to enhance professional development
      and gain confidence during the internship.

PMID- 21177143
TI  - Eager 'weavers': designing assessment for an online environment.
AB  - As more and more Australian universities move their courses into blended learning
      environments (BLEs), it is important that strategies be devised to monitor
      teaching practices and student learning. In 2008, five large Australian
      universities were given an ALTC (Australian Learning and Teaching Council) grant
      to address the area of teacher peer review (PR). This paper shows evidence from
      one of the universities (The University of Technology, Sydney) where a case study
      was undertaken to optimise teacher peer review in a BLE. The project involved an
      innovative approach of interdisciplinary PR between an academic from the Faculty
      of Nursing, Midwifery and Health and an academic from the Faculty of Arts and
      Social Science (FASS). As a result of this collaboration, the online assessment
      in the nursing subject was radically changed with a greater percentage of the
      marks awarded to online activities. The design took more 'up front' effort by the
      coordinator, as is usually the case in online preparation, but results have shown
      that students who had previously relied heavily on directions from their tutors
      throughout the semester, were now taking on more responsibility for their own
      learning and for the learning of fellow students.

PMID- 21177144
TI  - Effect of Cushing's syndrome - Endogenous hypercortisolemia on cardiovascular
      autonomic functions.
AB  - Cushing's syndrome is associated with increased cardiovascular morbidity and
      mortality. It's also associated with other cardiac risk factors like
      hypertension, diabetes mellitus and obesity. Cardiovascular autonomic function
      impairment could predict cardiovascular morbidity and mortality. Twenty five
      patients with Cushing's syndrome without diabetes and twenty five age matched
      healthy controls underwent a battery of cardiovascular autonomic function tests
      including deep breath test, Valsalva test, hand grip test, cold pressor test and
      response to standing from lying position. The rise in diastolic blood pressure on
      hand grip test and diastolic BP response to cold pressor test in Cushing's
      patients were significantly less compared to healthy controls (9.83 +/- 3.90 vs
      20.64 +/- 9.55, p<0.001 and 10.09 +/- 4.07 vs 15.33 +/- 6.26, p<0.01
      respectively). The E:I ratio on deep breathing test was also less in the patients
      in comparison to controls (1.36 +/- 0.21 vs 1.53 +/- 0.19, p<0.01). Seven
      patients underwent the same battery of tests 6 months after a curative surgery
      showing a trend towards normalization with significant improvement in expiratory
      to inspiratory ratio and sinus arrhythmia delta heart rate. To conclude, this
      study showed that chronic endogenous hypercortisolism in Cushing's is associated
      with an impaired sympathetic cardiovascular autonomic functioning. After a
      curative surgery, some of the parameters tend to improve.

PMID- 21177146
TI  - Nasogastric application of topical Ankaferd Blood Stopper for bleeding from
      primary esophageal adenocarcinoma in a child with disseminated intravascular
      coagulation.

PMID- 21177145
TI  - A novel and specific method for the determination of aristolochic acid-derived
      DNA adducts in exfoliated urothelial cells by using ultra performance liquid
      chromatography-triple quadrupole mass spectrometry.
AB  - Aristolochic acid nephropathy (AAN) is associated with the prolonged exposure to
      nephrotoxic and carcinogenic aristolochic acids (AAs). DNA adducts induced by AAs
      have been proven to be critical biomarkers for AAN. Therefore, accurate and
      specific quantification of AA-DNA adducts is important. In this study, a specific
      method using ultra performance liquid chromatography-tandem mass spectrometry
      (UPLC-MS/MS) was developed and applied for the determination of 7-(deoxyadenosin
      N(6)-yl)aristolactam I (dA-AAI) in exfoliated urothelial cells of AA-dosed rats.
      After the isolation from urine samples, DNA in urothelial cells were subjected to
      enzymatic digestion and solid-phase extraction on a C(18) Sep-Pak cartridge for
      the enrichment of DNA adducts. The sample extracts were analyzed by reverse-phase
      UPLC-MS/MS with electrospray ionization in positive ion mode. The quantification
      of the AA-DNA adduct was performed by using multiple reaction monitoring with
      reserpine as internal standard. The method provided good accuracy and precision
      with a detection limit of 1 ng/ml, which allowed the detection of trace of dA-AAI
      in exfoliated urothelial cells. After one-month oral dose of AAI at 10 mg/kg/day,
      2.1+/-0.3 dA-AAI per 10(9) normal dA was detected in exfoliated urothelial cells
      of rats. Compared to the traditional methods such as (32)P-postlabelling and HPLC
      with fluorescence detection, the developed UPLC-MS/MS method is more specific and
      rapid with a retention time of 4 min. The outcome of this study may have clinical
      significance for diagnosing and monitoring AA-associated disease because
      detection of DNA adducts in exfoliated urothelial cells is non-invasive and
      convenient.

PMID- 21177147
TI  - The Israel Police DNA database: recognizing the capability of databases in
      providing investigative leads.

PMID- 21177148
TI  - Anterior hip subluxation following fixation of a T-shaped acetabular fracture
      through an extended iliofemoral approach.
AB  - We report the case of a 34-year-old female patient who, six week following her
      acetabular fracture ORIF through an extended iliofemoral approach, presented with
      anterolateral incomplete dislocation of the femoral head. In the absence of joint
      incongruence as demonstrated on radiographs and CT images, a capsular tightening
      was performed via the anterior Hueter approach. This capsular plasty stabilized
      the hip for 2 years, but gradual osteoarthritis deterioration resulted in the
      need for arthroplasty. At the 2-year follow-up, this secondary arthroplasty
      showed satisfactory result. The substantial muscle exposure of the lateral aspect
      of the acetabulum and the circumferential capsulotomy related to the use of the
      iliofemoral approach were retained as factors promoting this complication. In
      case early postoperative mobilization is impossible, temporarily maintaining the
      limb in abduction and flexion can be recommended after an extended iliofemoral
      approach with circumferential capsulotomy.

PMID- 21177149
TI  - Posterior approach and dislocation rate: a 213 total hip replacements case
      control study comparing the dual mobility cup with a conventional 28-mm metal
      head/polyethylene prosthesis.
AB  - INTRODUCTION: Dislocation is a frequent complication of total hip arthroplasties
      (THA) especially in older patients, especially when using a posterior approach.
      In these cases, dual mobility (DM) cups developed by Gilles Bousquet in 1975 can
      be indicated to reduce this complication risk. HYPOTHESIS: Dual mobility cups
      reduce the rate of dislocation in primary total hip arthroplasty using posterior
      approach in a single-surgeon series. AIM: Test this hypothesis in a controlled
      study to compare the rate of dislocation in primary total hip arthroplasties done
      in patients over 50 years old either with a dual mobility cup or a conventional
      metal-on-polyethylene 28-mm diameter head. PATIENTS AND METHODS: Two consecutive
      series of primary total hip replacements were performed by a single surgeon using
      a posterolateral approach. The piriformis tendon was left intact. The DM series
      included 105 patients who underwent arthroplasty between January 2005 and June
      2007 with a dual mobility cup (60 women and 45 men, mean age 76.6+/-5.65 years
      old [53-93]). The control series (S series) included 108 patients who underwent
      arthroplasty (56 women and 52 men, mean age 74.2+/-5.9 years old [53-87]) with a
      conventional 28-mm polyethylene cup between January 2003 and June 2005. All hip
      replacements included a 28-mm metal-polyethylene cup and a 12-14-mm Morse taper.
      Both groups were comparable for gender, diagnosis, body mass index, type of
      anesthesia and ASA score distribution. All patients included in this series had a
      minimum follow-up of 1 year. RESULTS: There were no dislocations in the DM series
      and five early dislocations (before the third month) in the S series for a rate
      of 4.63%. Although the rate of dislocation was higher in the S series (4.63% vs
      0%), the difference was barely significant (P=0.0597). DISCUSSION: This study
      comparing the incidence of dislocations after THA with conventional or dual
      mobility cups, shows that even using a posterior approach and in older patients,
      dual mobility cups increase stability with no postoperative dislocations.
      Although results are barely significant, a larger series should confirm the
      benefit of this implant. In this series, morbidity was not increased with dual
      mobility cups. LEVEL OF EVIDENCE: Level III: retrospective case-control study.

PMID- 21177151
TI  - Treatment for metastatic nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a specific entity different from head and neck
      carcinoma. Incidence is higher in South-East Asia and North Africa. Prognosis,
      especially for locally advanced stages (IIB - IVB) and metastasis, remains poor:
      more than third of cases will present local and/or metastatic recurrence. Overall
      5-year survival for all NPC stages ranges from 50% to 70%. The role of
      chemotherapy in metastasis is well established, and remains an important
      palliative treatment, although no randomized trial has been reported comparing
      the different chemotherapy regimens. As 1(st)-line treatment, platin-based
      regimens seems optimal; in 2(nd) line and after progression under platins, there
      is no consensus: monotherapy with drugs such as gemcitabine, capecitabine or
      taxanes has been the most widely tested, with acceptable results. Future trials
      should integrate targeted therapy, in the light of overexpression of EGFR1 and C
      kit in NPC. The present study presents a review of the literature concerning the
      various studies of metastatic NPC.

PMID- 21177150
TI  - Folate intake and the risk of colorectal cancer: a systematic review and meta
      analysis.
AB  - INTRODUCTION: Folic acid fortification and supplementation to prevent neural tube
      defects has led to concerns regarding increased risk of colorectal cancer. The
      results of existing studies have been inconclusive. The purpose was to examine
      the relationship between level of folate intake and the incidence of colorectal
      cancer. METHODS: A systematic review and meta analysis were conducted. MEDLINE,
      Embase, and SCOPUS were searched from inception to October 2009 with the
      following search terms "folic acid," "folate", "colorectal cancer," "colon
      neoplasms," rectal neoplasms." Observational studies in adult populations were
      included that defined levels of folate intake and incidence of colorectal cancer.
      RESULT: Out of 6427 references, 27 studies met our inclusion criteria. The
      summary risk estimate for case control studies comparing high versus low total
      folate intake was 0.85 (CI 95% 0.74-0.99) with no significant heterogeneity among
      studies. Similarly, for cohort studies, the resulting summary risk estimate for
      high versus low dietary folate intake was 0.92 (CI 95% 0.81-1.05) with no
      significant heterogeneity. However, defining what represents a higher intake of
      folic acid is difficult as there is variability in the upper limit of folic acid
      intake used in the studies. DISCUSSION: These results suggest that higher folate
      intake levels offer a reduction in one of the perceived risks associated with
      developing colorectal cancer. These data can serve to help reassure women
      planning a pregnancy to increase folic intake during the preconception period to
      levels sufficient to prevent neural tube defects.

PMID- 21177152
TI  - A syndrome first described in 1936, still relevant today.

PMID- 21177153
TI  - Ultrasonic in vivo measurement of ocular surface expansion.
AB  - Our aim was to ascertain whether the ultrasonic measurement of longitudinal
      corneal apex displacements carried out in a proper headrest is a credible method
      of ocular pulse (OP) detection. To distinguish between longitudinal movements of
      the eye globe treated as a rigid body and ocular surface expansion caused by the
      variations of the eye-globe volume, two ultrasound distance sensors were applied
      to noninvasively measure displacements of cornea and sclera. The same sensors
      were used to examine the influence of the anterio-posterior movements of a fixed
      head on the registration of corneal apex pulsation. In both experiments, ECG
      signals were synchronically recorded. Time, spectral, and coherence analyses
      obtained for four healthy subjects showed that the ocular surface expansion due
      to pulsatile ocular blood flow (POBF) is the main component of longitudinal
      corneal displacement. Ocular surface pulsation is always affected by the head
      movement. However, there exist some unique properties of signals, which help to
      distinguish between head and eye movements. A rigid headrest and a bite bar are
      required to stabilize the head during OP measurement. Ultrasonic technique
      enables noninvasive and accurate in vivo measurement of corneal pulsation, which
      could be of interest for indirectly estimating intraocular pressure propagation
      and POBF component.

PMID- 21177154
TI  - Single-trial subspace-based approach for VEP extraction.
AB  - A signal subspace approach for extracting visual evoked potentials (VEPs) from
      the background electroencephalogram (EEG) colored noise without the need for a
      prewhitening stage is proposed. Linear estimation of the clean signal is
      performed by minimizing signal distortion while maintaining the residual noise
      energy below some given threshold. The generalized eigendecomposition of the
      covariance matrices of a VEP signal and brain background EEG noise is used to
      transform them jointly to diagonal matrices. The generalized subspace is then
      decomposed into signal subspace and noise subspace. Enhancement is performed by
      nulling the components in the noise subspace and retaining the components in the
      signal subspace. The performance of the proposed algorithm is tested with
      simulated and real data, and compared with the recently proposed signal subspace
      techniques. With the simulated data, the algorithms are used to estimate the
      latencies of P(100), P(200), and P(300) of VEP signals corrupted by additive
      colored noise at different values of SNR. With the real data, the VEP signals are
      collected at Selayang Hospital, Kuala Lumpur, Malaysia, and the capability of the
      proposed algorithm in detecting the latency of P(100) is obtained and compared
      with other subspace techniques. The ensemble averaging technique is used as a
      baseline for this comparison. The results indicated significant improvement by
      the proposed technique in terms of better accuracy and less failure rate.

PMID- 21177155
TI  - Head and trunk segment moments of inertia estimation using angular momentum
      technique: validity and sensitivity analysis.
AB  - Classical models to estimate the head and trunk (HT) moments of inertia (I) are
      limited to populations from which the anthropometric measures were obtained. The
      purposes of this study were to determine if the angular momentum technique can be
      used to estimate subject-specific HT's I values and test its validity and
      sensitivity. Twenty-three adults who participated in this study were divided into
      three morphological groups according to their body mass index (BMI). Using the
      proposed technique, the HT's I values were estimated for the whole sample and
      compared to three well-known methods to test its validity. The sensitivity of the
      proposed method was verified while applied to individuals with different BMI
      (i.e., lean, normal, and obese). The angular momentum technique gave I values
      within the range of those of the three methods for the entire sample. Statistical
      differences were identified between the lean and obese groups in relative radii
      of gyration for the anteroposterior and mediolateral axes ( P<0.05). Since the
      proposed technique makes no assumption on the mass distribution and segments'
      geometry, it appeared to be more sensitive to body morphology changes in
      estimating the HT's I values in lean and obese subjects compared to the classical
      methods.

PMID- 21177156
TI  - Triboelectricity in capacitive biopotential measurements.
AB  - Capacitive biopotential measurements suffer from strong motion artifacts, which
      may result in long time periods during which a reliable measurement is not
      possible. This study examines contact electrification and triboelectricity as
      possible reasons for these artifacts and discusses local triboelectric effects on
      the electrode-body interface as well as global electrostatic effects as common
      mode interferences. It will be shown that most probably the triboelectric effects
      on the electrode-body interface are the main reason for artifacts, and a
      reduction of artifacts can only be achieved with a proper design of the electrode
      body interface. For a deeper understanding of the observed effects, a
      mathematical model for triboelectric effects in highly isolated capacitive
      biopotential measurements is presented and verified with experiments. Based on
      these analyses of the triboelectric effects on the electrode-body interface,
      different electrode designs are developed and analyzed in order to minimize
      artifacts due to triboelectricity on the electrode-body interface.

PMID- 21177157
TI  - Distributed adaptive tracking control for synchronization of unknown networked
      Lagrangian systems.
AB  - This paper investigates the cooperative tracking control problem for a group of
      Lagrangian vehicle systems with directed communication graph topology. All the
      vehicles can have different dynamics. A design method for a distributed adaptive
      protocol is given which guarantees that all the networked systems synchronize to
      the motion of a target system. The dynamics of the networked systems, as well as
      the target system, are all assumed unknown. A neural network (NN) is used at each
      node to approximate the distributed dynamics. The resulting protocol consists of
      a simple decentralized proportional-plus-derivative term and a nonlinear term
      with distributed adaptive tuning laws at each node. The case with nonconstant NN
      approximation error is considered. There, a robust term is added to suppress the
      external disturbances and the approximation errors of the NNs. Simulation
      examples are included to demonstrate the effectiveness of the proposed
      algorithms.

PMID- 21177158
TI  - Linfinity-gain adaptive fuzzy fault accommodation control design for nonlinear
      time-delay systems.
AB  - In this paper, an adaptive fuzzy fault accommodation (FA) control design with a
      guaranteed L(infinity)-gain performance is developed for a class of nonlinear
      time-delay systems with persistent bounded disturbances. Using the Lyapunov
      technique and the Razumikhin-type lemma, the existence condition of the
      L(infinity) -gain adaptive fuzzy FA controllers is provided in terms of linear
      matrix inequalities (LMIs). In the proposed FA scheme, a fuzzy logic system is
      employed to approximate the unknown term in the derivative of the Lyapunov
      function due to the unknown fault function; a continuous-state feedback control
      strategy is adopted for the control design to avoid the undesirable chattering
      phenomenon. The resulting FA controllers can ensure that every response of the
      closed-loop system is uniformly ultimately bounded with a guaranteed L(infinity)
      gain performance in the presence of a fault. Moreover, by the existing LMI
      optimization technique, a suboptimal controller is obtained in the sense of
      minimizing an upper bound of the L(infinity)-gain. Finally, the achieved
      simulation results on the FA control of a continuous stirred tank reactor (CSTR)
      show the effectiveness of the proposed design procedure.

PMID- 21177159
TI  - Retraction: Serum Fluoride Level and Children's Intelligence Quotient in Two
      Villages in China.
AB  - The paper entitled "Serum Fluoride Level and Children's Intelligence Quotient in
      Two Villages in China" by Xiang Quanyong et al, which was published online on 17
      December 2010, has been withdrawn.

PMID- 21177160
TI  - [Benign fibrous histiocytoma involving the skull: a case report and literature
      review].
AB  - OBJECTIVE: Benign fibrous histiocytomas (BFH) represent a rare group of tumors
      with a common origin from the tissue histiocytes, often causing pain and space
      occupying effect. BFH of bone causes diagnostic difficulties due to its atypical
      clinical symptoms, radiographic features and cytological characteristics, which
      can be easily confused with other benign lesions such as non-ossifying fibroma
      (NOF), giant cell tumor (GCT), and fibrous dysplasia. The lesions are prone to
      relapse, and the patients often show poor response to radiotherapy and
      chemotherapy, therefore radical lesion resection should be the therapeutic target
      of this disease. This paper reported a case of BFH involving the skull and
      reviewed the associated literatures.

PMID- 21177161
TI  - Asymmetric dimethylarginine upregulates the expression of ACAT-1 in THP-1
      macrophage-derived foam cells.
AB  - OBJECTIVE: To investigate the effects of asymmetric dimethylarginine (ADMA) on
      ACAT-1 expression and cholesterol content in THP-1-derived macrophages and foam
      cells. METHODS: THP-1 cells were induced to differentiate into macrophages and
      further into foam cells. The macrophages and foam cells were exposed to different
      concentrations (0, 3.75, 7.5, 15, and 30 umol/L) of ADMA for varying time lengths
      (6, 12, and 24 h), and the changes in ACAT-1 mRNA and protein levels in the cells
      were measured with RT-PCR and Western blotting. The cellular cholesterol content
      was measured with enzyme-linked colorimetry assay. RESULTS: In THP-1-derived
      macrophages and foam cells, the expression levels of ACAT-1 mRNA and protein and
      cellular cholesterol content increased significantly in response to ADMA
      treatment in a time- and concentration-dependent manner. CONCLUSION: ADMA may
      play an important role in inducing foam cell formation from macrophages. ACAT-1
      inhibition targeting the macrophages and foam cells may serve as a potential
      therapeutic target in the treatment of atherosclerosis.

PMID- 21177162
TI  - [Validation of an improved Demons deformable registration algorithm and its
      application in re-contouring in 4D-CT].
AB  - OBJECTIVE: To validate the efficiency and accuracy of an improved Demons
      deformable registration algorithm and evaluate its application in contour
      recontouring in 4D-CT. METHODS: To increase the additional Demons force and
      reallocate the bilateral forces to accelerate convergent speed, we propose a
      novel energy function as the similarity measure, and utilize a BFGS method for
      optimization to avoid specifying the numbers of iteration. Mathematical
      transformed deformable CT images and home-made deformable phantom were used to
      validate the accuracy of the improved algorithm, and its effectiveness for
      contour recontouring was tested. RESULTS: The improved algorithm showed a
      relatively high registration accuracy and speed when compared with the classic
      Demons algorithm and optical flow based method. Visual inspection of the
      positions and shapes of the deformed contours agreed well with the physician
      drawn contours. CONCLUSION: Deformable registration is a key technique in 4D-CT,
      and this improved Demons algorithm for contour recontouring can significantly
      reduce the workload of the physicians. The registration accuracy of this method
      proves to be sufficient for clinical needs.

PMID- 21177163
TI  - [Impact of muscle strength on knee joint stability in static loading].
AB  - OBJECTIVE: To study the in vivo stability of normal and anterior cruciate
      ligament (ACL)-injured knee joint before and after epidural anesthesia under 134
      N pre-loading and evaluate the influence of muscular tension on the knee
      stability. METHODS: Eight volunteers with unilateral ACL rupture and normal
      contralateral knee were enrolled in this study. CT (3D) images and 2 orthogonal
      images of the knee were captured at 0 degrees , 30 degrees , 60 degrees , and 90
      degrees  under 134 N pre-loading. The orthogonal images were used to recreate the
      in vivo knee positions at each of the targeted flexion angles by 2D/3D
      registration to analyze the tibial translation data. RESULTS: The anterior tibia
      translation of both the intact and ACL-injured knees after anesthesia was
      significantly different from that before anesthesia at all the angles (P<0.05).
      The anterior tibial translation of the intact knee after anesthesia increased by
      1.7 mm at 0 degrees , 2.7 mm at 30 degrees , 2.6 mm at 60 degrees , and 2.3 mm at
      90 degrees , as compare to the increase of ACL-injured knee by 4.2 mm, 2.6 mm,
      1.2 mm, and 1.6 mm, respectively. CONCLUSION: The muscular tension has evident
      influence on the knee stability in static loading.

PMID- 21177164
TI  - [Construction of a lentivirus interfering vector targeting Cyc1 and its
      interfering efficiency in nasopharyngeal carcinoma cells].
AB  - OBJECTIVE: To analyze the expression of Cyc1 in nasopharyngeal carcinoma (NPC)
      and evaluate the interfering efficiency of a lentivirus interfering vector
      targeting Cyc1 in NPC cells. METHODS: Microarray technique was used to examine
      the expression of Cyc1 in NPC tissues. Real-time PCR was utilized to confirm the
      high expression of Cyc1 in NPC tissues and NPC cell lines. The recombinant Cyc1
      shRNA-expressing plasmid (pLentiU6/Cyc1-shRNA) was stably transfected into NPC
      cells, and the interfering efficiency against Cyc1 was evaluated by quantitative
      RT-PCR. RESULTS: The result of microarray showed that Cyc1 was highly expressed
      in NPC tissues compared to noncancerous nasopharyngeal tissues, as confirmed by
      Real-time PCR. All of the 8 NPC cells showed a high expression of Cyc1, among
      which 5-8F cells showed the highest expression. Sequence analysis indicated that
      the recombinant plasmid pLentiU6/Cyc1-shRNA was successfully constructed and
      could significantly and stably suppress the expression of Cyc1 in NPC cells.
      CONCLUSION: Cyc1 is highly expressed in NPC cells. The lentivirus vector
      constructed can markedly inhibit the expression of Cyc1 in NPC cells, which
      provides assistance in the investigation of the function and molecular mechanism
      of Cyc1 in NPC.

PMID- 21177165
TI  - [Transplantation of adipose tissue-derived stem cells promotes soft tissue wound
      repair in rats].
AB  - OBJECTIVE: To assess the effect of local and intravenous transplantation of
      adipose tissue-derived stem cells (ADSCs) in promoting soft tissue wound healing
      in rats. METHODS: ADSCs isolated from the adipose tissues of SD rats were
      cultured in vitro, and the third-passage cells were identified for their capacity
      of multipotent differentiation. Eighteen SD rats with 1.8 cm2 dorsal full
      thickness soft tissue defects (0.5 cm deep) were randomized into 3 groups to
      receive injection of 3.0*106 DiI-labeled ADSCs via the tail vein, local injection
      of the cells at the wound site, or injection of saline (control). The wound
      healing was evaluated on days 3, 7, 11, and 14 postoperatively. On day 24 after
      the injury, tissue samples at the wound site were collected for fluorescent
      microscopy and HE staining. RESULTS: The ADSCs obtained were capable of
      adipogenic, osteogenic, and neurogenic differentiation in vitro. ADSCs
      transplantation significantly promoted wound healing as compared to the control
      group. Obvious wound contracture was observed in the local injection group on day
      3 and in the intravenous injection group on day 7. Fluorescence microscopy
      revealed DiI-positive cells in the healing wound, and HE staining showed a
      greater tissue thickness at the wound in the two ADSCs transplantation groups.
      Compared to the control group, the two ADSCs transplantation groups showed more
      gland-like structures and better neovascularization at the wound. CONCLUSION:
      ADSCs can significantly promote wound healing in rats, and local injection of
      ADSCs allows more rapid and obvious wound healing than tail veil injection of the
      stem cells.

PMID- 21177166
TI  - [Nanometer detection of self-assembly morphology of sodium hyaluronate injection
      on mica].
AB  - OBJECTIVE: To detect the self-assembly morphology of sodium hyaluronate injection
      on mica using atomic force microscopy(AFM). METHODS: Atomic force microscopy with
      nanometer resolution was used to observe the self-assembly morphology of
      different concentrations of sodium hyaluronate injection on mica at room
      temperature. RESULTS: The self-assembly morphology of 0.001, 0.01, and 0.1 mg/ml
      sodium hyaluronate injection on mica featured piebald, reticular and dendritic
      structures, respectively. At 1 and 5 mg/ml, sodium hyaluronate injection
      displayed bacilliform and spherical structures on mica, respectively; the
      diameter and height of the particles of 5 mg/ml sodium hyaluronate was 197.97+/
      78.48 nm and 30.79+/-18.67 nm, significantly greater than those of 0.1 mg/ml
      sodium hyaluronate injection (49.52+/-11.93 nm and 5.37+/-1.59 nm, respectively,
      P<0.05). CONCLUSION: The self-assembly morphology of sodium hyaluronate injection
      on mica varies with its concentration. The piebald and reticular structure may
      facilitate the function of sodium hyaluronate, and the dendritic feature
      resembles the representative model of diffusion-limited aggregation (DLA).

PMID- 21177167
TI  - [Changes in cerebral blood flow during mastication in patients receiving
      prosthesis insertion for repairing maxillary defect].
AB  - OBJECTIVE: To investigate the changes in cerebral blood flow in patients with
      maxillary defect treated with prosthesis insertion. METHODS: Thirty patients with
      maxillary defect receiving obturator prosthesis insertion were enrolled with
      another 30 subjects without dentition defect as the control. The cerebral blood
      flow rate was recorded before and at 5 and 10 min during mastication, and the
      results were analyzed statistically. RESULTS: There was no significant difference
      in Vs, Vd or Vm between the two groups at the time points for measurement.
      CONCLUSION: The blood supply by the middle cerebral artery is similar between the
      patients receiving obturator prosthesis insertion for maxillary defect and the
      subjects with full denture.

PMID- 21177168
TI  - [IgG radiolabelling with (99m)Tc by tricarbonyl method and its biodistribution in
      mice].
AB  - OBJECTIVE: To synthesize the complex fac-[99(m)Tc(CO)3(H2O)3](+) for labeling IgG
      and investigate the in vitro stability of 99(m)Tc(CO)3(H2O)3-IgG and its
      biodistribution in mice. METHODS: fac-[99(m)Tc(CO)3(H2O)3](+) was synthesized and
      its radiochemical purity determined using polyamide membrane chromatography. IgG
      was directly labeled with fac-[99(m)Tc(CO)3(H2O)3](+) and the labeling ratio was
      determined using chromatography. The stability of 99(m)Tc(CO)3(H2O)3-IgG in human
      serum albumin and normal saline was evaluated. 99(m)Tc(CO)3(H2O)3-IgG was
      injected via the tail vein into 9 mice at the dose of 3.7*104 Bq/100 ul, and
      SPECT image was obtained at 2, 4 and 12 h after the injection. The mice were
      sacrificed at these time points to measure the radioactivity and calculate the
      %ID/g in each organ. RESULTS: Fac-[99(m)Tc(CO)3(H2O)3](+) had a radiochemical
      purity of 82.48% and remained stable in vitro at room temperature within 4 h. The
      labeling ratio of 99(m)Tc(CO)3(H2O)3-IgG was 57.04% with a radiochemical purity
      exceeding 90%. In the solution of human serum albumin, the labeled IgG maintained
      a stable radiochemical purity, but in normal saline, its radiochemical purity was
      lowered to 20% at 24 h. After injection in mice, the labeled IgG was deposited
      mainly in the liver, spleen, kidneys, and the blood pool showed a sustained
      radioactivity. CONCLUSION: 99(m)Tc(CO)3(H2O)3-IgG prepared in this study has good
      stability in vitro and in vivo in 24 h and shows a biodistribution pattern
      similar to that of IgG protein in vivo. The intermediate fac
      [99(m)Tc(CO)3(H2O)3](+) can meet the experimental requirement for labeling
      monoclonal antibodies and polypeptides.

PMID- 21177169
TI  - [Effects of simvastatin on plasma SOD, MDA and 8-iso-PGF2alpha in patients with
      stable angina].
AB  - OBJECTIVE: To observe the effects of simvastatin on plasma superoxide dismutase
      (SOD), malonaldehyde (MDA) and 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) as
      well as uric acid (UA) and serum lipids in patients with stable angina. METHODS
      Eighty-five patients with stable angina were divided into 4 groups, including
      hyperlipemia treatment group (HLT), hyperlipemia control group (HLC),
      normolipemia treatment group (NLT), and normolipemia control group (NLC). All the
      patients received routine treatment according to the guideline of CHD treatment,
      and those in the treatment groups were given Simvastatin (40 mg) every night,
      whereas those in the control group received placebo for 3 months. Before and
      after the treatments, the levels of plasma 8-iso-PGF2alpha were measured by
      enzyme-linked immunosorbent assay, and the plasma levels of SOD and MDA were
      detected by colorimetric method. LDL, HDL, TC, TG, and UA were also measured
      biochemically. RESULTS Compared with the control group, both of the treatment
      groups showed significantly increased levels of SOD and decreased MDA, 8-iso
      PGF2alpha, UA and plasma lipids after the treatments (P<0.05). CONCLUSION In
      patients with coronary heart disease, simvastatins can decrease plasma lipids,
      inhibit lipid peroxidations, and promote the clearance of free radicals, thereby
      alleviating the oxidative stress.

PMID- 21177171
TI  - [Effect of obstructive sleep apnea hypopnea syndrome on arterial stiffness].
AB  - OBJECTIVE: To assess the effect of obstructive sleep apnea hypopnea syndrome
      (OSAHS) on brachial-ankle pulse wave velocity (b-aPWV) in untreated diagnosed
      patients. METHODS: This study involved 24 consecutive male patients with newly
      diagnosed untreated OSAHS (aged 39.13+/-8.31 years) and 22 normal male
      individuals (aged 39.59+/-10.86 years) matched for age and body mass index.
      Carotid and extremities ultrasound were performed in all the subjects, and none
      of them had atherosclerosis, arterial calcification, or aneurysm. No subject had
      a history of hypertension, coronary heart disease or stroke. All the subjects
      underwent arterial stiffness evaluation by means of b-aPWV measurements. RESULTS:
      The b-aPWV in OSAHS patients was significantly higher than that in normal
      subjects (1346.86+/-123.48 vs 1237.91+/-84.46, P<0.01), and the rate of positive
      b-aPWV in OSAHS patients was significantly higher (13/24 vs 1/22, P<0.01).
      CONCLUSION: The value and positive rate of b-aPWV in OSAHS patients are higher
      than those in normal people, suggesting increased arterial stiffness in OSAHS
      patients.

PMID- 21177170
TI  - [Autophagy is involved in 6-OHDA-induced dopaminergic cell death].
AB  - OBJECTIVE: To study the role of autophagy in the death of dopaminergic neurons
      induced by 6-hydroxydopamine (6-OHDA). METHODS: Rat models of Parkinson disease
      (PD) were established by stereotaxic administration of 6-OHDA (8 MUg) into the
      unilateral substantia nigra par compact (SNpc). Autophagosomes in the SNpc were
      observed with transmission electron microscopy (TEM), and the expression of
      autophagy-related protein LC3 was determined with immunofluorescence (IF) assay.
      RESULTS: Under TEM, the autophagosomes were found in the ipsilateral SNpc 6-24 h
      after 6-OHDA injection, which suggested the activation of autophagy. IF assay
      showed significantly increased LC3 expression in 6-OHDA-damaged TH-positive
      neurons as compared to the control group. CONCLUSIONS: The increase of
      autophagosomes and activation of autophagy may play a role in dopaminergic neuron
      death induced by 6-OHDA.

PMID- 21177172
TI  - [Distribution of HCV genotypes in volunteer blood donors in Guangzhou].
AB  - OBJECTIVE: To determine the distribution of HCV genotypes among volunteer blood
      donors in Guangzhou. METHODS: Six-nine HCV RNA-positive samples were collected
      from volunteer blood donors in Guangzhou. NS5B fragments of HCV were amplified
      followed by DNA sequencing and phylogenetic analysis. RESULTS: HCV genotypes were
      determined for 67 samples. Among them, the subtypes 1b, 2a, 3a, 3b, 6a and 6n
      were detected at the frequencies of 37.31%, 4.48%, 7.46%, 4.48%, 44.78% and
      1.49%, respectively. CONCLUSION: HCV 1b and 6a are the most predominant two
      subtypes among volunteer blood donors in Guangzhou.

PMID- 21177173
TI  - [Exogenous Nkx2-5 gene expression induces the expression of cardiac markers
      during P19 cell differentiation in vitro].
AB  - OBJECTIVE: To investigate the role of homeobox gene Nkx2-5 in cardiac myogenesis.
      METHODS: Two P19 cell lines, namely cells transfected with exogenous expression
      of Nkx2-5 gene and non-transfected cells, were cultured in suspension for 4 days
      to induce cell aggregation, and the cell aggregates were transferred to the Petri
      dish for further adherent culture. On days 4, 8, 12 and 16 of adherent culture,
      the expressions of alpha-sarcomeric actin (alpha-SA) and cardiac troponin T
      (cTnT) protein were detected by immunocytochemistry, and the mRNA expressions of
      GATA-4, alpha-myosin heavy chain (alpha-MHC) and atrial natriuretic factor (ANF)
      genes by RT-PCR. RESULTS: In the transfected cells, alpha-SA and cTnT protein
      expressions were detected on days 8, 12 and 16 of adhere culture, and their
      expressions increased gradually with time. alpha-SA and cTnT expression was
      significantly higher on day 16 than on day 8 of culture (P<0.01). RT-PCR analysis
      of the transfected cell showed the presence of GATA-4 expression on day 4 of
      adherent culture, and the expression increased on days 8 and 12 but decreased on
      day 16. ANF and alpha-MHC expressions were found on days 8, 12, and 16,
      increasing gradually over time and showing significant differences from those on
      day 4 (P<0.05 or P<0.01). The expression of alpha-MHC was significantly higher on
      days 12 and 16 than on day 8 (P<0.05 or P<0.01), and ANF expression was
      significantly higher on day 16 than on days 8 and 12 (P<0.01). The non
      transfected cells were negative for the expressions of all these genes.
      CONCLUSION: Exogenous expression of Nkx2-5 gene can induce P19 cells to express
      cardiac markers in vitro.

PMID- 21177174
TI  - [ERK1/2 mediates edaravone-triggered protection against myocardial damage induced
      by isoprenaline in H9c2 cells].
AB  - OBJECTIVE: To explore the effect of extracellular signal regulated kinase 1/2
      (ERK1/2) on edaravone (EDA)-triggered protection against myocardial toxicity
      induced by isoprenaline (ISO) in H9c2 myocardial cells (H9c2 cells). METHODS:
      H9c2 cells were exposed to ISO at different concentrations to establish a cardiac
      toxicity model induced by persistent excitation of beta1 receptor. EDA was added
      before ISO as a pretreatment. PD-98059, an ERK1/2 inhibitor, was administered 1 h
      prior to EDA to inhibit the phosphorylation of ERK1/2. Cell viability was
      measured using cell counter kit (CCK-8). The expressions of p-ERK1/2 and t-ERK1/2
      were tested by Western blotting. Mitochondrial membrane potential (MMP) was
      detected by Rhodamine123 (Rh123) staining and photofluorography. RESULTS:
      Exposure of H9c2 cells to 80 umol/L ISO for 24 h down-regulated ERK1/2
      phosphorylation and repressed MMP. Pretreatment with 10-40 umol/L EDA for 1 h
      inhibited ISO-induced myocardial toxicity and pretreatment of 40 umol/L EDA
      partially rescued ERK1/2 phosphorylation and MMP level. PD-98059 abolished
      cardiac protection of EDA, leading to myocardial toxicity and MMP loss.
      CONCLUSION: EDA can protect H9c2 cells against myocardial injury induced by ISO
      by suppressing ISO-triggered inhibition of ERK1/2 activation.

PMID- 21177175
TI  - [Comparison of two methods for primary culture of epithelial cells from human
      bioptic tissue of nasopharyngeal carcinoma].
AB  - OBJECTIVE: To compare two methods for primary culture of the epithelial cells
      from human bioptic specimens of nasopharyngeal carcinoma (NPC), and preliminarily
      study the biological characteristics of the primarily cultured cells. METHODS:
      Thirty-three bioptic specimens were collected from patients with pathologically
      confirmed NPC who received no previous radiotherapy or chemotherapy. Seventeen
      samples were cultured using tissue culture method, and tissue predigestion
      culture was used for the other 16 samples. The cells were cultured in
      Keratinocyte-SFM medium containing 2% fetal bovine serum. The two culture methods
      were compared for successful rate, attachment time and average time of cell
      growth. The biological features of the cultured cells were observed by reverse
      microscope, cytokeratin immunocytochemistry, growth curve and survival analysis.
      RESULTS: The successful rate, attachment time and days for cell growth of the
      tissue culture method and tissue predigestion culture method were 23.5% (4/17) vs
      62.5% (10/16), 4.47+/-0.48 h vs 7.88+/-1.01 h, and 13.75+/-1.5 days vs 8.3+/-4.55
      days, respectively, showing significant differences between the two methods
      (P<0.05). The cells resulting from tissue predigestion method, with a average
      survival of 62.72 days, were characterized by a fusiform morphology with large
      nuclei, multiple nucleoli, and cytokeratins positivity. In contrast, the cells
      obtained by tissue culture method showed multilayer alignment without distinct
      cell structures and failed to grow consistently. CONCLUSION: Compared with tissue
      culture method, tissue predigestion cell culture results in high successful rate
      and requires shorter cell growth time with longer attachment time. Keratinocyte
      SFM medium supplemented with low concentrations of FBS is suitable for the growth
      of primarily cultured epithelial cells from NPC biopsy samples in vitro.

PMID- 21177176
TI  - [Dosimetry of electron-beam chest-wall irradiation after mastectomy in patients
      with left breast cancer].
AB  - OBJECTIVE: To evaluate the dosimetric advantages of postmastectomy electron-beam
      chest-wall irradiation after left mastectomy in patients with breast cancer.
      METHODS: Electron-beam chest-wall irradiation and tangential field irradiation
      were planned using Pinnacle7.4f planning systems for 42 patients with left breast
      cancer after mastectomy. The total prescribed dose for both plans was 5000 cGy/25
      fractions. The dose volume histogram was used to compare the dosimetry of the
      clinical target volume (CTV) and the organs at risk such as the heart and
      ipsilateral lung. RESULTS: The maximum dose (Dmax) of the CTV of electron beam
      chest-wall irradiation plans was significantly higher than that of tangential
      field irradiation plans (5562+/-61 vs 5402+/-82 cGy, t=6.10, P<0.05). The CTV of
      the electron beam chest-wall irradiation plans showed better heterogeneity than
      that of the tangential field irradiation plans, with heterogeneity index of
      1.18+/-0.03 and 1.13+/-0.18, respectively (t=6.50, P<0.05). Electron beam chest
      wall irradiation plans had also a better conformal index of the CTV than
      tangential field irradiation plans (0.77+/-0.17 vs 0.57+/-0.17, t=3.49, P<0.05).
      The V40 of the ipsilateral lung, the maximum dose of the heart, V30 and V40 of
      the heart in the electron beam chest-wall irradiation plans were smaller than
      those of the tangential field irradiation plans [(5.86+/-3.68)% vs (8.73+/
      3.26)%, t=-2.27, P<0.05; 4839+/-388 cGy vs 5095+/-176 cGy, t=-2.32, P<0.05;
      (2.58+/-1.50)% vs (7.20+/-2.62)%, t=-4.70, P<0.05; (1.74+/-1.23)% vs (4.20+/
      2.51)%, t=-3.50, P<0.05]. CONCLUSION: Compared with the tangential field
      irradiation plans, electron-beam chest-wall irradiation has better coverage index
      of the CTV and can decrease the high-dose volume of the normal tissue, but shows
      a poorer habituation index of the CTV.

PMID- 21177177
TI  - [Gefitinib inhibits alpha-smooth muscle actin expression in mice with bleomycin
      induced lung fibrosis].
AB  - OBJECTIVE: To evaluate the effect of epidermal growth factor receptor tyrosine
      kinase inhibitor, gefitinib, on the expression of alpha-smooth muscle actin
      (alpha-SMA) in mice with lung fibrosis induced by bleomycin. METHODS: Thirty male
      BALB/c mice were randomly divided into control, bleomycin, and bleomycin plus
      gefitinib groups. The mice in the control group were subjected to intratracheal
      administration of normal saline, those in bleomycin group received bleomycin (3
      mg/kg) intratracheally, and those in bleomycin plus gefitinib group received oral
      gefitinib (20 mg/kg administering) plus intratracheal bleomycin administration.
      All the mice were sacrificed 14 days after the treatments, and the left lung was
      examined pathologically with HE staining and Masson staining and also
      immunohistochemically for assay of the total EGFR, phosphorylated EGFR and alpha
      SMA. The right lungs were sampled for RT-PCR to detect the mRNA levels of alpha
      SMA. RESULTS: Gefitinib administration lessened lung fibrosis induced by
      bleomycin and significantly reduced lung collagen accumulation. The
      phosphorylation of EGFR in the pulmonary mesenchymal cells and epithelial cells
      and the expression levels of alpha-SMA mRNA and protein were inhibited by
      gefitinib treatment in mice with intratracheal administration of bleomycin
      (P<0.05). CONCLUSION: Gefitinib offers protection against lung fibrosis induced
      by bleomycin in mice probably by inhibiting the downstream signals of EGFR and by
      downregulating the expression of alpha-SMA.

PMID- 21177178
TI  - [Transfection of hBcl-2 gene protects the liver against ischemia/reperfusion
      injury in rats during liver transplantation].
AB  - OBJECTIVE: To study the effect of hBcl-2 gene transfer on rat liver against
      ischemia-reperfusion injury, and explore the feasibility of this approach to
      reduce ischemia-reperfusion injury in liver transplantation. METHODS: We
      constructed the replication-deficient recombinant adenoviruses Adv-EGFP and Adv
      Bcl-2 and transfected them into 293 cells and packaged into adenovirus particles
      for amplification and purification. The empty plasmid vector virus was
      constructed similarly. Male SD rats were randomized into Adv-Bcl-2-transfected
      group, Adv-EGFP-transfected group, ischemia-reperfusion group, and sham-operated
      group, and liver allograft transplantation model was established by sleeve
      method. In the transfected groups, the recombinant viruses were administered by
      perfusion through the portal vein, and the ischemia-reperfusion and sham-operated
      groups received no treatment. Real-time quantitative PCR and Western blotting
      were used to detect the mRNA and protein expressions of bcl-2 in the liver tissue
      of each group, and at 0, 60 and 180 min after reperfusion, serum AST, LDH, and
      MDA levels were measured. Histological changes of the liver cells were evaluated
      by HE staining. RESULTS: Bcl-2 mRNA and protein expressions in Adv-Bcl-2
      transfected group, as compared with those in Adv-EGFP-transfected group and
      control group, were significantly increased (P<0.01); the serum levels of AST,
      LDH and MDA in Adv-Bcl-2-transfected group were significantly lower than those of
      Adv-EGFP-transfected group and ischemia-reperfusion group (P<0.05 or 0.01).
      Compared with the sham-operated group, Adv-Bcl-2 treatment group showed lessened
      edema and vacuolar degeneration of the liver cells without patches or spots of
      necrosis. In ischemia-reperfusion and Adv-EGFP group, HE staining revealed
      hepatic lobular destruction and extensive liver cell swelling, enlargement,
      vacuolar degeneration, edema and occasional focal necrosis. CONCLUSION: Adv-Bcl-2
      transfection can induce the expression of bcl-2 gene to reduce ischemia
      reperfusion injury of the liver graft in rats.

PMID- 21177179
TI  - [Ozone therapy combined with sulfasalazine delivered via a colon therapy system
      for treatment of ulcerative colitis].
AB  - OBJECTIVE: To assess the therapeutic effect of ozone therapy combined with
      sulfasalazine sulfasalazine delivered via a colon therapy system in the treatment
      of distal ulcerative colitis. METHODS: This prospective randomized controlled
      clinical trial involved 54 patients with mild to moderate active distal
      ulcerative colitis, who were randomize into 3 groups in accordance with the
      inclusion criteria (n=18). Each group was given sulfasalazine at the daily dose
      of 2 g, and in colon therapy group and ozone therapy plus sulfasalazine therapy
      group, sulfasalazine was delivered via a colon therapy system on a daily basis;
      the control group received sulfasalazine via retention enema only. At 0, 2, and 4
      weeks of the treatment, colonoscopy was performed to evaluate the disease
      activity, and biopsy samples were obtained at 0 and 4 weeks for histological
      examination. RESULTS: In comparison with colon therapy group and control group,
      ozone therapy plus colon therapy resulted in more rapid alleviation of the
      clinical symptoms and better histological improvement without any adverse
      effects. CONCLUSION: Ozone therapy combined with sulfasalazine delivered via a
      colon therapy system is feasible and effective for treatment of ulcerative
      colitis.

PMID- 21177180
TI  - [Effect of the degree of muscle relaxation on motor-evoked potential elicited by
      transcranial electrical stimulation in spine surgery].
AB  - OBJECTIVE: To study the effect of the degree of muscle relaxation on motor-evoked
      potential elicited by transcranial electrical stimulation in patients undergoing
      spine surgery. METHODS: Sixty ASA I or II patients undergoing spine surgery were
      randomly divided into 5 groups (n=12). After an initial intubation, continuous
      cisatracurium infusion was administered with continuous monitoring of T1. The
      infusion dose was adjusted according muscle relaxation monitoring, and different
      muscle relaxation degrees were maintained in the 5 groups. The band and latency
      of D1 in motor-evoked potential was observed with also subjective assessment of
      the muscle relaxation. RESULTS: Significant differences in the band and latency
      were noted in groups I and II compared with the reference values, but not in
      groups III, IV and V. Subjective assessment revealed significant differences
      between groups IV and V and groups I and III in terms of the number of cases with
      poor muscle relaxation. CONCLUSION: T1 value between 10% and 15% is sufficient
      for MEP monitoring and allows the maintenance of good muscle relaxation during
      spine surgery.

PMID- 21177181
TI  - [A modified endovascular treatment for longitudinal intracranial aneurysm].
AB  - OBJECTIVE: To study the surgical approach and curative effect of the
      "interlocking basket" technique in interventional therapy for longitudinal
      intracranial aneurysm. METHODS: Thirty-eight Hunt and Hess Grade I-III patients
      with longitudinal intracranial aneurysm underwent interventional therapy using
      the "interlocking basket" technique. During the operation, the aneurysm was
      divided into two segments based on its length and occluded with two coils. The
      first coil with a transverse diameter matching that of the aneurysm was deployed
      to form a "basket", which was densely occluded, and a portion of this coil out of
      the "basket" was interlocked with the second coil to form another "basket"
      crossing the aneurysmal neck to prevent the coils from escaping till the neck of
      the aneurysm was densely occluded. RESULTS: Thirty-five aneurysms (92.1%) were
      completely embolized, and 3 (7.9%) were 95% embolized. No coil escaping from the
      aneurysm neck or other complications occurred. Twenty-five patients were
      discharged with a GOS score of 5 (65.8%), 7 (18.4%) with a score of 4, and 6
      (15.8%) had a score of 3. In the follow-up for 3-25 months after the
      embolization, angiography was performed in 28 cases, and recurrence was found in
      2 cases (7.14%). CONCLUSION: The "interlocking basket" technique can increase the
      coil stability in longitudinal intracranial aneurysm and allows reliable block of
      the aneurysm neck and dense embolization of the aneurysm to improve the clinical
      outcomes of the patients.

PMID- 21177182
TI  - [Expression of c-myb in reflux esophagitis, Barrett esophagus and esophageal
      adenocarcinoma].
AB  - OBJECTIVE: To investigate the expression of c-myb in reflux esophagitis, Barrett
      esophagus and esophageal adenocarcinoma. METHODS: The expression levels of c-myb
      in the esophageal mucosa tissue of patients with reflux esophagitis, Barrett
      esophagus and esophageal adenocarcinoma were detected by real-time fluorescent
      quantitative RT-PCR. RESULTS: The expression levels of c-myb mRNA in Barrett
      esophagus and esophageal adenocarcinoma tissues was significantly higher than
      that in normal and reflux esophagitis esophageal tissue (P<0.05 or 0.01), and
      increased progressively with the development of reflux esophagitis into Barrett
      esophagus and esophageal adenocarcinoma. CONCLUSIONS: The expression level of c
      myb mRNA is closely related with the development of Barrett esophagus and
      esophageal adenocarcinoma, and may be used as a valuable index for monitoring the
      early onset and intervention of Barrett esophagus and esophageal adenocarcinoma.

PMID- 21177183
TI  - [Changes of the elastic fibers and collagen fibers during the development and
      progression of experimentally induced tongue carcinoma in hamsters].
AB  - OBJECTIVE: To investigate the relationship between the extracellular matrix (ECM)
      and neoplastic progression in hamster with tongue cancer. METHODS: Forty-eight
      specimens of hamster tongue cancer were divided into control group (n=6) and
      experimental group (n=42). The pathological grade of the specimens was assessed
      (including 3 stages, namely atypical hyperplasia, carcinoma in situ and early
      invasive carcinoma). The sections of the tongue were stained with Masson and
      aldehyde-fuchsin (AF) staining for microscopic observation of the elastic fiber
      and collagen fiber changes. RESULTS: Within the connective tissue cores (CTC) of
      the papillae in the control group was a framework of numerous and fine Gomrori's
      aldehyde fuchsin-positive elastic fibers. But in the stages of dysplasia and
      carcinoma in situ, these elastic fibers decreased and further diminished in the
      CTC in early invasive carcinoma. In dysplasia and carcinoma in situ stages, most
      of the elastic fibers collapsed with scattered elastic fibers, and the elastic
      fibers decreased significantly in early invasive carcinoma. The control group
      showed a significantly greater number of elastic fibers in the experimental
      group. The collagen fiber was obviously increased and irregularly arranged in
      dysplasia and carcinoma in situ stage; in early invasive carcinoma, the collagen
      fibers became thicker with deposition in the lamina propria. CONCLUSION: An
      excessive deposition of collagen fiber and reduction of the elastic fibers is an
      important factor contributing to the development of tongue carcinoma in hamsters.

PMID- 21177184
TI  - [Association of coxsackie virus infection and T lymphocyte subset changes with
      type 1 diabetes].
AB  - OBJECTIVE: To investigate the relationship between coxsackievirus infection and
      type 1 diabetes mellitus (T1DM), and observe the changes of T lymphocyte subsets
      in the development of T1DM. METHODS: We detected Coxsackievirus RNA by reverse
      transcription PCR, and measured the change in T-lymphocyte subsets by flow
      cytometry in 22 cases of newly diagnosed T1DM (group I), 30 patients with
      diabetes for some time (group II), and 30 healthy subjects (group III). RESULTS:
      The positivity rate of coxsackie virus RNA in groups I, II, and III was 55.55%,
      23.33%, and 6.67%, respectively, showing a significant difference among the 3
      groups (P<0.01). Patients with upper respiratory tract infection had a higher
      positivity rate for coxsackie virus RNA than those without upper respiratory
      tract infection in group I (P<0.05). Compared with the control group, the
      percentage of CD3, CD4 and CD4/CD8 ratio decreased significantly in groups I and
      II (P<0.01 or P<0.05). CD3, CD4 and CD4/CD8 tended to increase in group II in
      comparison with group I, and there was an significant difference in CD3 and CD4
      between the two groups (P<0.01 or P<0.05). Compared with the control group and
      CVBRNA-negative group, CVBRNA-positive group showed significantly lowered CD3,
      CD4, CD8 and CD4/CD8 (P<0.01 or P<0.05). CONCLUSION: The occurrence and
      development of type 1 diabetes is closely related to coxsackie virus infection,
      and the changes in T lymphocyte subsets serves as a probable mechanism of its
      pathogenicity.

PMID- 21177185
TI  - [Effect of electroacupuncture on pain threshold and spinal NR2B subunit
      expression in a rat model of neuropathic pain].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on pain threshold and
      spinal NR2B subunit expression in a rat model of neuropathic pain due to chronic
      compression injury (CCI) of the sciatic nerve and explore the analgesic mechanism
      of EA. METHODS: Male SD rats weighing 200-280 g were randomly divided into 4
      groups (n=10), namely the sham-operated group, CCI group, EA+CCI group, and sham
      EA+CCI group. All the rats underwent tests of the mechanical withdrawal threshold
      and thermal threshold. On day 13 after the surgery, all the rats were decapitated
      to collect the L4-6 segments of the spinal cord to examine NR2B expression using
      Western blotting. RESULTS: The postoperative mechanical withdrawal threshold and
      thermal threshold were significantly lowered in CCI, EA+CCI and sham EA+CCI
      groups as compared to those before the surgery (P<0.05). EA obviously alleviated
      the hypersensitivity in the rats with CCI and inhibited spinal NR2B expressions
      (P<0.05). No significant differences were found in the mechanical withdrawal
      threshold, thermal threshold or spinal NR2B subunit expression between CCI group
      and sham EA+CCI group (P>0.05). CONCLUSION: EA may alleviate neuropathic
      hypersensitivity partially by inhibiting NR2B expression in the spinal cord of
      rats with neuropathic pain resulting from CCI of the sciatic nerve.

PMID- 21177186
TI  - [Application of membrane protein-based two-dimensional electrophoresis in
      chondrocyte- related investigations].
AB  - OBJECTIVE: To explore the feasibility of membrane protein-based two-dimensional
      electrophoresis (2-DE) in the investigations of chondrocyte-related diseases and
      its complementarity with total protein-based 2-DE. METHODS: Knee cartilage
      samples were obtained to isolate the chondrocytes with type II
      collagenase/hyaluronidase digestion. The membrane proteins and total proteins
      were extracted and loaded separately onto PH3.0-10.0 non-linear gel strip for 2
      DE analysis. The qualities of membrane protein-based 2-DE gels were evaluated,
      and the difference between the distribution profiles of the membrane protein
      spots and that of the total protein were observed and their complementarities
      were evaluated. RESULTS: Membrane protein-based 2-DE generated high-quality gel
      images, and on each gel 412.3+/-13.5 protein spots were identified. These spots
      were distributed in the region of isoelectric point pH 5.0-9.0. In the gel images
      generated by the total proteins, 564.3+/-5.9 protein spots were identified in
      each image, and the spots were distributed in the region of isoelectric point pH
      3.0-7.0. CONCLUSION: Membrane protein-based 2-DE of the chondrocytes can generate
      high-quality gel images, and the isoelectric distribution of the protein spots is
      complementary to that of total protein, which provides valuable information for
      chondrocyte-related diseases.

PMID- 21177187
TI  - [Transurethral enucleation of the prostate for treatment of benign prostatic
      hyperplasia in patients less than 50 years old].
AB  - OBJECTIVE: To evaluate the therapeutic effect of transurethral enucleation of the
      prostate for treatment of benign prostatic hyperplasia in patients below 50 years
      of age. METHODS: Twelve patients with benign prostatic hyperplasia patients (mean
      age 48.2 years, range 46-49 years) underwent transurethral enucleation of the
      prostate. The middle lobe and two lateral lobes were enucleated with the
      preprosthetic sphincter and anterior fibromuscular stroma preserved during the
      operation. The patients were followed up to evaluate the lower urinary tract
      symptoms and sexual activity after the surgery. RESULTS: The 12 patients were
      followed up for 3 to 6 months. The symptoms of lower urinary tract obstruction
      were improved obviously after the surgery, and the International Prostate Symptom
      Score (IPSS) decreased from 24+/-5.1 to 8.8+/-1.4 and peak urine flow rate (Qmax)
      increased from 8.1+/-4.2 ml/s to 20.1+/-4.2 ml/s at 3 months postoperatively. All
      the 12 cases had residual urine (12-44 ml) preoperatively, but after the surgery,
      only 4 still had residual urine of less than 30 ml. All the patients had normal
      erection function postoperatively, and 10 had normal ejaculation; the other 2
      patients recovered normal ejaculation 3 and 5 months after the operation,
      respectively. CONCLUSIONS: Transurethral enucleation can alleviate the low
      urinary tract obstruction symptom and improve the sexual function by avoiding
      preprosthetic sphincter injury in relatively young patients with benign prostatic
      hyperplasia.

PMID- 21177188
TI  - [Effect of intracerebroventricular injection of rAAV-HIF-1alpha on hippocampal
      neuronal apoptosis in a rat model of Alzheimer disease].
AB  - OBJECTIVE: To observe the effect of intracerebroventricular injection of rAAV-HIF
      1alpha on hippocampal neuronal apoptosis in a rat model of Alzheimer disease
      (AD). METHODS: Thirty-two male SD rats (250-300 g) were randomized into 4 groups
      (n=8), including the normal control group without any treatment, AD model group
      with right intracerebroventricular injection of 2 ul Abeta25-35 (10 mg/m1), sham
      operated group with right intracerebroventricular injection of 2 ul normal
      saline, and AD+ rAAV-HIF-1alpha group with right intracerebroventricular
      injection of 10 ul rAAV-HIF-1a (1*1012 v.g./m1) one week after Abeta25-35
      injection. The rats were sacrificed to detect the expression of HIF-1alpha and
      apoptosis of hippocampal neurons 5 weeks after Abeta25-35 or saline injection.
      RESULTS: Western blotting showed that the expression of HIF-1alpha was
      significantly higher in AD+rAAV-HIF-1alpha group (451.59+/-34.39) than in normal
      control group (229.05+/-41.28) and sham-operated group (216.29+/-37.08) (P<0.05)
      without significant difference between the latter two groups. The apoptotic ratio
      of the hippocampal neurons was significantly higher in AD model group ([19.49+/
      2.59]%) than in normal control group ([5.41+/-0.75]%) and sham-operated group
      ([5.28+/-0.66]%) in (P<0.05), and intracerebroventricular injection of rAAV-HIF
      1alpha resulted in a significant reduction of the apoptotic ratio in the AD rats
      ([12.07+/-2.06]%) (P<0.05). CONCLUSION: Intracerebroventricular injection of rAAV
      HIF-1alpha can inhibit hippocampal neuronal apoptosis in the rat model of AD.

PMID- 21177189
TI  - [Applied anatomy of the inguinal region and laparoscopic inguinal hernia repair].
AB  - OBJECTIVE: To investigate the regional anatomy of the inguinal region and
      abdominal ring and provide accurate anatomic basis for the clinical application
      of total peritoneum intraperitoneal onlay mesh (TPIPOM). METHODS: The structures
      of the inguinal region and those surrounding the abdominal ring of 18 cadavers
      (11 males and 7 females, 36 sides) were dissected to measure the lengths from the
      nerves and vessels to the corresponding anatomical landmarks. RESULTS: The
      average distances from the point where the iliohypogastric nerve (IHN) ran
      through the obliquus internus abdominis to anterosuperior iliac spine and from
      the point where the IHN ran through the aponeurosis of the external oblique
      muscle of the abdomen to the superior margin of the symphysis pubica were 4.10+/
      0.89 cm and 5.02+/-1.46 cm, respectively. The average distances from the point
      where the ilioinguinal nerve (IGN) ran through the obliquus internus abdominis to
      the anterosuperior iliac spine and from the point where IGN ran through the
      aponeurosis of the external oblique muscle of the abdomen to the superior surface
      of the tuberculum pubicum were 3.09+/-0.81 cm and 3.84+/-0.89 cm, respectively.
      We established the regional anatomy model of the structures surrounding the
      abdominal ring. CONCLUSION: The quantitative measurement of important structures
      of the inguinal region and establishment of the regional anatomy model of the
      surrounding structures of the abdominal ring can provide a valuable reference to
      reduce intraoperative and postoperative complications of TPIPOM.

PMID- 21177190
TI  - [A follow-up study of the development of factor VIII inhibitor in Chinese
      patients with hemophilia A].
AB  - OBJECTIVE: To study the incidence and characteristics of coagulation factor VIII
      (FVIII) inhibitor development in Chinese patients with hemophilia A. METHODS: A
      24-month continuous follow-up was conducted among 215 Chinese patients with
      hemophilia A to observe the characteristics of FVIII inhibitor development and
      the clinical characteristics of the patients. RESULTS: The cumulative incidence
      of FVIII inhibitor development in 24 months was 11.6% (25/215) in these patients.
      Of the 25 patients with FVIII inhibitor development, 18 (72%) had low-titer
      inhibitors and 7 (28%) had high-titer inhibitors. The patients developed the
      inhibitors after a median of 150 exposure days at a median age of 25 years (6-59
      years). Fifteen patients with low-titer inhibitors (median 1.25 BU/ml) showed
      gradual disappearance of the inhibitors in a median of 10 months (6-15 months)
      without any treatment, and 5 patients with high-titer inhibitors (median 100
      BU/ml) remained positive in 24 months; the other 5 FVIII inhibitor-positive cases
      showed no significant changes. In the 25 patients developing FVIII inhibitors,
      the bleeding frequency increased significantly (P=0.025), and in 18 of the
      patients who continued to use FVIII products, a significant increase in the dose
      of medication was noted (P=0.015), but the number of target joints did not
      increase in 24 months (P=0.329). CONCLUSION: The incidence and characteristics of
      factor VIII inhibitor development differ between Chinese patients with hemophilia
      A and those in developed countries.

PMID- 21177191
TI  - [Thoracic aortic replacement with concomitant endoluminal stent grafting for
      DeBakey type I aortic dissection].
AB  - OBJECTIVE: To evaluate the therapeutic effect and safety of thoracic aortic
      replacement with concomitant endoluminal stent grafting in the treatment of
      DeBakey type I aortic dissection. METHODS: From September 2007 to January 2010, 6
      patients with DeBakey type I aortic dissection (including one with aortic
      dissection relapse) received ascending aortic (or Bentall) and total aortic arch
      replacement and simultaneous stent graft implantation into the descending aorta.
      Multi-slice spiral CT scans (MSCT) were performed in each patient regularly after
      the surgery. Cardio-pulmonary bypass including deep hypothermic circulatory
      arrest with selective antegrade cerebral perfusion were used during the surgery.
      RESULTS: All the patients recovered smoothly after the surgical procedure without
      serious complications. The time of cardiopulmonary bypass ranged from 208 to 291
      min (mean 242 min), arrest time of the ascending aortic was 112-194 min (mean 145
      min), and selective cerebral perfusion time was 63-102 min (mean 76 min). The
      patients were followed up for 4-32 months (mean 15.5 months), and MSCT revealed
      smooth blood flow in the prosthesis, complete thrombus formation in the false
      lumen in the perigraft space and shrinkage of the distal false lumen without
      internal fistula or stent dislocation. CONCLUSION: Thoracic aortic replacement
      with concomitant endoluminal stent grafting is a safe and effective treatment of
      DeBakey type I dissection.

PMID- 21177192
TI  - [Effect of percutaneous vertebroplasty and kyphoplasty in the treatment of
      osteoporotic vertebral compression fractures].
AB  - OBJECTIVE: To analyze the therapeutic effects of percutaneous vertebroplasty
      versus percutaneous kyphoplasty for treatment of osteoporotic vertebral
      compression fractures. METHODS: Fifteen patients (24 vertebrae) underwent
      percutaneous vertebroplasty and 15 (18 vertebrae) received percutaneous
      kyphoplasty for osteoporotic vertebral compression fractures. The postoperative
      recovery of the anterior vertebral body height, visual analogue scale (VAS) and
      locomotor activity before and after the operations were compared between the two
      groups. RESULTS: All the patients were available for the follow-up lasting for 3
      15 months (average 7 months). In the vertebroplasty group, the VAS score
      decreased from 8.68 preoperatively to 1.74 postoperatively and to 1.13 at the
      final follow-up. The VAS score in the kyphoplasty group decreased from 8.62
      preoperatively to 1.72 postoperatively and to 1.21 at the final follow-up. Both
      vertebroplasty and kyphoplasty were effective in improving the anterior vertebral
      body height, but kyphoplasty showed a better effect. None of the patients
      developed serious complications associated with the operations. CONCLUSION:
      Percutaneous vertebroplasty and percutaneous kyphoplasty both achieve rapid and
      significant improvement of back pain in patients with osteoporotic vertebral
      compression fractures, but kyphoplasty shows a better effect in terms of
      vertebral body height restoration and cement leakage reduction.

PMID- 21177193
TI  - [Magnetic resonance imaging characteristics of spinal cord lesions and brain
      abnormalities in Chinese patients with neuromyelitis optica].
AB  - OBJECTIVE: To analyze the magnetic resonance imaging (MRI) characteristics of
      neuromyelitis optica (NMO) in Chinese patients. METHODS: We retrospectively
      reviewed the MRI films of 61 patients with NMO (including 57 female and 4 male
      patients) admitted in our department. RESULTS: Of these patients, 39 (79.6%)
      showed positivity for serum aquaporin-4 (AQP4) antibody. On MRI, 18 patients
      showed involvement of the cervical cord alone, 27 had both cervical and thoracic
      segment involvement, and 16 displayed thoracic segment involvement. The lesions
      appeared linear (9 cases), diffuse (23 cases), or both (29 cases), mostly located
      axially with occasional lateral distribution. Thirty-nine of the 61 patients
      (63.9%) had brain abnormalities, 31 presented with supratentorial lesions (mostly
      in the juxtacortical, subcortical, deep white matter and lateral ventricle
      adjacent regions, n=27), 15 showed infratentorial lesions (mostly in the
      preiaqueduct-fourth ventricular-central canal, n=13), and 7 had supra- and
      infratentorial lesions simultaneously. CONCLUSION: NMO has complex MRI
      presentation, and linear lesions in the spinal cord and preiaqueduct-fourth
      ventricular-central canal lesions, where AQP4 is high expressed, can be
      characteristic for NMO. MRI and AQP4 antibody detection are suggested for
      suspected cases for early diagnosis.

PMID- 21177194
TI  - [Astrocytic gap junction in the hippocampus of rats with lithium pilocarpine
      induced epilepsy].
AB  - OBJECTIVE: To investigate the changes in the gap junction of the hippocampal
      astrocytes of a rat model of lithium pilocarpine-induced epilepsies. METHODS:
      Lithium chloride and pilocarpine were injected intraperitoneally in SD rats to
      induce status epilepticus (SE). At 2, 12, 24 h and 3, 7, 15, 30 and 60 days after
      SE, the rats were sacrificed to observe the pathological changes in the
      hippocampus using Nissl staining. Immunohistochemistry for GFAP and connexin43
      (CX43) were used to evaluate reactive astrogliosis and the changes in the
      astrocytic gap junctions. RESULTS: SE induced by lithium and pilocarpine lasted
      for 6-30 h, and after a seizure-free period of about 30-45 days, the rats
      developed spontaneous recurrent seizures. Nissl staining showed that the most
      obvious neuronal damage occurred 12-24 h after seizure onset. Reactive gliosis
      began to be progressively prominent after 7 days till the end of the observation.
      GFAP expression increased 7 days after SE induction, intensified at 30 days, and
      became the most prominent at 60 days. In control rats, CX43 immunostaining was
      diffuse in the hippocampus; in the epileptic rats, diffuse CX43-positive
      varicosities appeared in the molecular layer and stratum oriens of the CA1 and
      CA3 areas 2 after seizure onset, and the number, length and immunostaining
      intensity of the varicosities increased at 12 h. These changes became the most
      prominent at 24 h after seizure onset, followed by gradual decrease of the
      immunoactivity, which was virtually absent till 30 and 60 days. CONCLUSION: The
      hippocampal astrocytic gap junction coupling increases in acute SE to maintain
      the stability of the extracellular microenvironment. The defects in gap junction
      coupling of the astrocytes in chronic temporal lobe epilepsy may contribute to
      the development of spontaneous seizures.

PMID- 21177195
TI  - [Protective effects of captopril against lung injury in rats with severe acute
      pancreatitis].
AB  - OBJECTIVE: To investigate the protective effects of captopril against lung injury
      in a rat model of severe acute pancreatitis (SAP). METHODS: Seventy-two male SD
      rats were randomized into sham-operated group (SO group), SAP group and captopril
      intervention group (CAP group). Serum amylase and myeloperoxidase (MPO) activity
      in the lung tissue were examined at 1, 6 and 12 h after the operation. TNF-alpha
      and AngII in the lung tissue were detected by ELISA, and the histopathological
      changes of the pancreas and lung were observed microscopically. RESULTS: The MPO
      activity , which was similar between SAP group and CAP group at 1 h, were
      significantly lowered in CAP group at 6 and 12 h (P<0.05). Serum amylase level
      and the levels of TNF-alpha and AngII in the lung tissue homogenate were all
      reduced significantly in CAP group as compared to those in SAP group (P<0.01).
      The pathological injury of the lung was obviously lessened in CAP group in
      comparison with that in SAP group. CONCLUSION: Captopril can ameliorate SAP
      induced lung injury in rats.

PMID- 21177197
TI  - [Value of serum soluble lectin-like oxidized low-density lipoprotein receptor-1
      (LOX-1) and LOX-1 mRNA in peripheral mononuclear cells in early diagnosis of
      acute coronary syndrome].
AB  - OBJECTIVE: To assess the value of serum soluble lectin-like oxidized low-density
      lipoprotein receptor-1 (LOX-1) levels and LOX-1 mRNA expression in peripheral
      blood mononuclear cells in early diagnosis of acute coronary syndrome (ACS).
      METHODS: Enzyme-linked immunosorbent assay was used to detect the levels of
      plasma ox-LDL and LOX-1 in 95 patients with ACS, 60 with stable angina pectoris
      (SAP) and 40 normal control subjects. The expression of LOX-1 mRNA in peripheral
      blood mononuclear cells was detected by RT-PCR in the 3 groups. RESULTS: The
      levels of ox-LDL, LOX-1 and LOX-1 mRNA in the peripheral blood mononuclear cells
      were significantly higher in ACS patients than in SAP patients and normal control
      subjects (P<0.05). In ACS group, the level of plasma ox-LDL was significantly
      correlated to serum LOX-1 and LOX-1 mRNA expression in peripheral mononuclear
      cells. CONCLUSION: The level of plasma soluble LOX-1 and LOX-1 mRNA in peripheral
      mononuclear cells are significantly increased in ACS, and when combined, they
      provide a useful means for detecting ACS in the prophase.

PMID- 21177196
TI  - [Combined detection of Epstein-Barr virus antibodies for serodiagnosis of
      nasopharyngeal carcinoma].
AB  - OBJECTIVE: To investigate the value of combined detection of Epstein-Barr virus
      (EBV) VCA/IgA, EA/IgA, Rta/IgG and EBNA1/IgA in serodiagnosis of nasopharyngeal
      carcinoma (NPC). METHODS: Serum samples obtained from 211 untreated patients with
      NPC and 203 non-NPC ENT patients were examined for the presence of VCA/IgA and
      EA/IgA by immunoenzymatic assay and for Rta/IgG and EBNA1/IgA by enzyme-linked
      immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve
      was generated to confirm the cutoff values of different antibodies. The
      evaluation indexes of combined detection of multiple antibodies used for
      serodiagnosis of NPC were calculated with compounded positive judgment method.
      RESULTS: Compared to a single antibody, combined detection achieved a higher
      sensitivity and specificity. The sensitivity of VCA/IgA + Rta/IgG + EBNA1/IgA
      (98.1%) was higher than the other 3 combinations with a specificity, accuracy,
      Youden index and positive predictive value (PPV) of 88.7%, 93.5%, 0.868 and
      90.0%, respectively. The combination of EA/IgA+Rta/IgG+EBNA1/IgA had the highest
      specificity (95.1%), accuracy (94.9%), Youden index (0.899) and PPV (95.2%), with
      a sensitivity of 94.8%, suggesting its higher accuracy in the serodiagnosis of
      NPC. Combined detection of the 4 antibodies had the highest sensitivity (98.6%)
      with a specificity, accuracy, Youden index and PPV of 88.2%, 93.5%, 0.868 and
      89.7%, respectively. CONCLUSIONS: Combined detection of Rta/IgG against immediate
      early antigens, EA/IgA against early antigens, VCA/IgA against late antigens, and
      EBNA1/IgA against latent antigens provides better understanding of the expression
      profiles of EBV lytic and latent antigens with excellent complementarity, and may
      serve as an optimal combination for NPC serodiagnosis.

PMID- 21177198
TI  - [A comparative study of laparoscopic fistal pancreatectomy and open distal
      pancreatectomy].
AB  - OBJECTIVE: To compare the clinical results of laparoscopic distal pancreatectomy
      (LDP) and open distal pancreatectomy (ODP), confirm the potential advantages of
      LDP. METHODS: The medical records of 30 consecutive patients who underwent LDP
      were reviewed and compared with those of 42 patients who underwent ODP. RESULTS:
      Operation time was longer for LDP than for ODP [(186.33+/-58.98 min) vs (149.29+/
      29.00 min), P=0.001], but blood loss [(223.33+/-143.68 ml) vs(251.19+/-103.29
      ml), P=0.341] and spleen-saving rate(42.3% vs 61.8%, P=0.192) were no significant
      difference between the 2 groups. Decreased postoperative bowel recovery time
      [(2.37+/-0.85 d) vs (2.81+/-0.67 d), P=0.016], oral intake time [(2.37+/-0.85 d)
      vs (2.81+/-0.67 d), P=0.016] and length of stay [(7.43+/-1.57 d) vs (9.67+/-1.41
      d), P=0.000] were seen in LDP group. However, the rate of postoperative
      pancreatic fistula (16.67% vs 21.43%, P=0.619) was no significant difference
      between the 2 groups. 3 cases of wound infection and 2 cases of lung related
      complication were occurred in ODP group, but none in LDP group. CONCLUSION: LDP
      is a safe and effective surgical approach, providing the same surgical results
      comparable to that of ODP, and substantially faster recovery. However, high
      requirement of laparoscopic technique and equipments limited its further clinical
      application.

PMID- 21177199
TI  - [Determination of rat serum emodin level by microemulsion liquid chromatography
      with direct sample loading].
AB  - OBJECTIVE: To establish a microemulsion liquid chromatography system with direct
      sample loading for determining the serum level of emodin in rats. METHODS: The
      separation was performed on C18 column (Hypersil BDS, 5 um,150 mm*4.6 mm) with
      the microemulsion mobile phase consisting of 3.3% (w/V) SDS, 6.6% (V/V) n-butyl
      alcohol, and 1.0% (V/V) octane and water. The flow rate was 1.0 ml/min and the
      detection wavelength was 254 nm. RESULTS: The linear range of emodin detection
      was 0.333-5.32 ug/ml. The average recovery was 99.65% with a RSD of 3.60%. The
      limit of quantification was 0.1386 ug/mL. CONCLUSION: Microemulsion liquid
      chromatography system with direct sample loading allows simple, accurate and
      rapid determination of emodin in rat serum.

PMID- 21177200
TI  - [Therapeutic effect of autologous bone marrow stem cell transplantation in the
      treatment of severe liver damage].
AB  - OBJECTIVE: To evaluate the effect of autologous bone marrow stem cell
      transplantation in the treatment of severe liver damage. METHODS: Autologous bone
      marrow (50 ml) was harvested from 6 patients aged 44 to 69 years admitted for
      severe liver damage. Human bone marrow stem cells (HMSCs) were isolated and
      transplanted in to the patients' liver. At l, 4, 8, and 12 weeks after the
      transplantation, the changes in ALT, ALB, Cr, TB, PT and the clinical symptoms of
      the patients were observed. RESULTS: The transplantation of autologous bone
      marrow stem cells resulted in obvious improvement of the liver function. At 12
      weeks after the transplantation, ALT was reduced from 98.4 IU/L to 41.5 IU/L, TB
      from 136.5 umol/L to 78.4 umol/L, Cr from 112.3 umol/L to 72.1 umol/L, and ALB
      rose from 23.3 g/L to 32.6 g/L. The survival of the patients was 100% at 12
      weeks, but one patient died at 7 months after the transplantation. The symptoms
      of the patients were also alleviated after the transplantation. At 12 weeks after
      transplantation, 3 patients reported improved appetite, 3 showed recovery of
      physical strength, and 2 showed lessened abdominal swelling. No serious adverse
      complications in association with the transplantation were found in the in 4
      patients available to the follow-up. CONCLUSION: Autologous bone marrow stem cell
      transplantation can improve the liver function of patients with severe liver
      damage without causing serious complications.

PMID- 21177202
TI  - [Hemorrhage during and after percutaneous nephrolithotomy via standard
      nephrostomy tract].
AB  - OBJECTIVE: To investigate the intra- and postoperative hemorrhage of percutaneous
      nephrolithotomy via the standard nephrostomy tract. METHODS: A retrospective
      analysis was conducted among 1578 patients undergoing percutaneous
      nephrolithotomy. During the operations, all the nephrostomy tracts were dilated
      to F24 size after successful puncture. The stones were shattered and removed by
      EMS lithotrity system. RESULTS: All the patients showed intra- and postoperative
      hemorrhage, and in 121 cases, blood transfusion was needed. In 18 patients, the
      operation had to be terminated for severe hemorrhage. The 8 patients with
      repeated bleeding were managed and cured by blood transfusion and medication. In
      another 2 cases, severe hemorrhage was found to result from false aneurysms by
      renal arteriography and managed by superselective embolization. CONCLUSION:
      Percutaneous nephrolithotomy through standard nephrostomy tract is safe and does
      not increase the risk of bleeding with careful operation.

PMID- 21177201
TI  - [Synchronous squamous cell carcinoma of the renal pelvis and squamous cell
      carcinoma of the ureter: report of two cases and review of literature].
AB  - OBJECTIVE: To study the clinicopathological characteristics of synchronous
      squamous cell carcinoma (SCC) of the renal pelvis and SCC of the ureter. METHODS:
      The clinical data of two cases of synchronous SCC of the renal pelvis and SCC of
      the ureter were retrospectively reviewed and analyzed. In case 1, a 68-year-old
      man with hematuria for a month, imaging modalities revealed a right renal pelvis
      tumor and a right distal ureter tumor. The patient underwent nephroureterectomy
      and excision of the bladder cuff. Case 2, a 60-year-old man with the complaint of
      lower abdominal pain and left flank pain for a month, was diagnosed as left
      distal ureteral stone in another hospital. Ureterolithotomy was performed and a
      ureteral tumor was found at the lower site of the stone intraoperatively. The
      pathological report demonstrated SCC, and the patient was transferred to our
      hospital for further treatment. We found a left renal mass invading the left
      hemicolon during surgery, and nephroureterectomy was performed with a bladder
      cuff excision, left hemicolon resection, and also complete lymph node dissection.
      Neither of patients received adjuvant radiotherapy/chemotherapy. RESULTS:
      Moderately differentiated SCC was reported in both of renal pelvis and ureter in
      case 1 and the tumor invaded the subepithelial connective tissue in the renal
      pelvis and superficial muscle in the ureter. In case 2, moderately differentiated
      SCC of the left renal pelvis with colon metastasis and poorly differentiated SCC
      of the ureter was reported with two retroperitoneal lymph node metastases. The
      two patients died from tumor recurrence and metastasis 5 and 6 months after the
      surgery, respectively. CONCLUSION: Synchronous SCC of the renal pelvis and SCC of
      the ureter are rare and has high likeliness of early recurrence and metastasis,
      often with poor prognosis.

PMID- 21177203
TI  - Late presentation of breast cancer in Aden, Yemen.
AB  - The aim of this study is to determine the frequency and characteristics of
      patients who presented with late stage breast cancer at Al-Amal Oncology Unit in
      Aden. It was conducted retrospectively in Aden, at Al-Amal Oncology Unit of Al
      Gamhouria Modern General Hospital, by reviewing all records of breast cancer
      patients at any stage and attended with histopathologically documented breast
      cancer from the time of establishment of the unit on December 1, 2007 to December
      31, 2009. The total number of documented breast cancer patients was 197 and
      classified according to the stage at presentation and after the exclusion of 21
      patients who were not staged. 118 patients with late inoperable stages were
      selected and carefully evaluated of their demographic characteristics and was
      found that they represented 67.0% of the total staged breast cancer patients.
      Most of these patients are in the reproductive age and residents of Aden
      governorate and neighboring governorates. Metastasis was mainly evident at the
      lymph nodes, bones, liver and lungs. The case fatality rate for late stage breast
      cancer is 8.5 per 100 patients. This study concludes that a high percentage of
      Yemeni patients in Aden presented with late stage breast cancer which led to the
      failure of possible curative surgical intervention and resulted to high
      metastatic disease and fatality rate. KEYWORDS: Late Presentation, Aden, Yemen,
      Breast Cancer, Stages.

PMID- 21177204
TI  - Hyperfractionated radiation therapy and concurrent chemotherapy for advanced head
      and neck cancer.
AB  - PURPOSE: To investigate the feasibility of combining hyperfractionated
      radiotherapy regimen with concomitant chemotherapy and to assess its toxicity in
      patients with advanced head and neck carcinoma (HNC). Progression free survival
      (PFS) and overall survival (OS) were set as secondary end points. PATIENTS AND
      METHODS: Between November 2003 and November 2007, 48 patients with stage III and
      IV HNC who met the eligibility criteria were enrolled in the study.
      Hyperfractionated Radiation consisted of 120 Gys twice daily, 6 hours apart, for
      a total of 69.6 Gys in 58 fractions over 6 weeks and boost of 6 Gys in 3
      fractions in case of residual disease. Three cycles of concurrent chemotherapy in
      the form of Cisplatin 75 mg/ m2 on day 1 and Fluorouracil 750 mg/m2 24 hour
      infusion on day 1-4 during weeks 1, 4 and 6 of irradiation. RESULTS: 48 patients
      have completed the treatment to date. The median radiation dose was 72 Gys
      including the boost to residual lymph node or primary site. The treatment was
      delivered in a median overall period of 54 days, with a recorded median delay of
      7 days. Grade 4 skin toxicity was experienced by 4.1% of patients only. Therapy
      was well tolerated (grade 3 mucositis in 21%, grade 4 in 26%, grade 3 leukopenia
      in 10%). Weight loss of more than 10 kg was reported in 10 (16.7%) of the cases.
      The most common late toxicity was mild to moderate xerostomia which was
      encountered in 34 (70.8%) cases and improved thereafter. Hypothyroidism was
      encountered in 7 (14.6%) of the cases. Complete response (CR) was observed in 40
      patients (83.3%). Partial response (PR) was achieved in the remaining 8 patients
      (16.7%). Disease relapse occurred in 9 patients (18.8%) after complete response
      and 2 patients developed progressive disease after partial response. 3 patients
      relapsed locally, 5 patients developed distant metastasis and 1 patient developed
      both local and distant metastasis. 2 patients (4.1%) died of treatment
      complications, 8 patients (16.7%) died with progressive locoregional, and
      metastatic disease. The 2- year disease free survival was 77% and the 2- year
      overall survival was 79%. CONCLUSION: Hyperfractionated radiotherapy and
      concurrent chemotherapy is tolerable. Results regarding LC and OS are encouraging
      as compared to conventional radiotherapy and concurrent chemotherapy.

PMID- 21177205
TI  - Population-based study of Hodgkin's lymphoma in Kuwait.
AB  - INTRODUCTION: Hodgkin lymphoma (HL) comprises about 25% of all malignant nodal
      lymphomas worldwide. Incidence of HL has been increasing in many countries around
      the world, in the western countries in particular. Cancer incidence variations in
      different ethnic groups in the same country can lead to some important
      information about the search of etiological factors. Some researchers found an
      association between ethnicity and increased risk of HL. In this study, we
      evaluated the epidemiologic and clinical characteristics of patients with HL and
      the HL subtypes in Kuwait who were diagnosed between 1998 and 2006 and we
      analyzed the changes in the incidence of HL over time based on age, sex, and
      ethnicity. MATERIAL AND METHOD: The Kuwait Cancer Control Center is a tertiary
      referral hospital and the only cancer hospital in the entire state of Kuwait. We
      identified 293 patients who were newly diagnosed with HL by histopathology
      between January 1, 1998, and December 31, 2006, at the Kuwait Cancer Control
      Center. Incidence data were crossvalidated with the population-based Cancer
      Registry of Kuwait. Clinical data were obtained by reviewing the patients'
      medical records. RESULTS: The median age at diagnosis was 39 years (range, 10-85
      years) for patients with cHL and 36 years (range, 14-51 years) for patients with
      NLPHL. The age-adjusted incidence rate was 2.1 cases (range, 1.2-2.9) per 100,000
      people per year in the period between 1998 and 2006. NLPHL and cHL were
      predominant in men with a male to female ratio of 2:1. However, the mean annual
      percentage change in HL incidence among Kuwaiti patients and non-Kuwaiti patients
      per year showed unexplained higher percentage in females both Kuwaiti and non
      Kuwaiti. cHL comprised 92.5% of all HL cases and NLPHL comprised 7.5%. Nodular
      sclerosis was the predominant histologic subtype of cHL (58.9%), whereas mixed
      cellularity was the second most frequent histologic subtype of cHL, (25.9%).
      CONCLUSION: Although the incidence of HL was slightly lower in Kuwait than the
      worldwide incidence; it was similar to Asian descent population. Incidence of HL
      varied in the same country among different ethnic subgroups. The mean annual
      percentage change increased in Kuwaiti and non-Kuwaiti females.

PMID- 21177206
TI  - Peripheral dose from a dual energy linear accelerator equipped with tertiary
      multileaf collimators and enhanced dynamic wedge.
AB  - Peripheral dose (PD) or the dose outside the geometrical boundaries of the
      radiation field is of clinical importance when anatomical structures with low
      dose tolerances might be involved(1). It is the aim of this study is to estimate
      the PD on linear accelerators on different wedge systems without multileaf
      collimator (MLC). Measurements were performed on a dual energy linear accelerator
      equipped with tertiary MLC and enhanced dynamic wedge (EDW). Measurements were
      made using an ionization chamber embedded in a Radiation Field Analyser (RFA-300)
      with the secondary collimator and MLC setting of 5x5, 10x10, 15x15, and 20x20
      cm2, and with the MLC fully retracted. The effects of SSD on PD were measured at
      three SSDs of 90, 100, and 110 cm for the irradiation fields of 5x5, 10x10,
      15x15, and 20x20 cm2 and the effects of the three different wedges (Upper wedge,
      Lower Wedge and Enhanced Dynamic Wedge) on PD were measured for 45 degrees 
      wedges with field size of 15x15 cm2. Data were taken from 3 cm to 24 cm away from
      the field edge. Results show that due to tertiary MLC, PD can be reduced by means
      of a factor of two to three at certain distance from the edge of the field
      compared with TG-36 data. In between the wedges, the PD was less for the EDW when
      compared with the upper and lower physical wedges. We conclude that the reduction
      in PD is significant in reducing or eliminating the need for external peripheral
      shielding to reduce the dose on affected critical organs.

PMID- 21177207
TI  - Proteomics approaches: new technologies and clinical applications in breast
      carcinomas.
AB  - Breast cancer is the most diagnosed cancer in women, accounting for approximately
      40,000 deaths annually in the USA. In Tunisia, the incidence of breast cancer is
      approximately 19 new cases per 100,000 women per year. Significant advances have
      been made in the areas of detection and treatment, but a significant number of
      breast cancers are detected late. The advent of proteomics provides the hope of
      discovering novel biological markers that can be used for early detection,
      prognosis, diagnosis, and therapy. Several proteomics technologies have been used
      to uncover molecular mechanisms associated with breast. INTRODUCTION: Breast
      cancer is a major health problem and one of the leading causes of death among
      women worldwide. Its incidence is steadily rising in developing countries. In
      Tunisia, the incidence of breast cancer is approximately 19 new cases per 100,000
      women per year(1). Invasive carcinomas represent 70-80% of all breast cancer and
      among these, infiltrating ductal carcinomas (IDCA) are the most aggressive forms
      and have a poor prognosis(2). Histopathologically identical breast cancers show a
      different biological behavior in terms of aggressiveness, progression, and
      response to therapy. Thus, there is a great need for new breast cancer biomarkers
      that might help detect this cancer at an earlier stage, to uncover prognostically
      distinct subclasses, and to provide best individual treatment(2). Currently, the
      search for specific cancer-related alterations are largely carcinoma at the
      global level to discover protein patterns that distinguish disease and disease
      free states with high sensitivity and specificity. Two dimensional gel
      electrophoresis coupled with mass spectrometry constitute a new proteomics based
      paradigm for detecting disease in pathology specimens and monitoring disease
      response to therapy. This review describes these proteomics technologies and
      their application in the analysis of breast carcinoma.

PMID- 21177209
TI  - Laryngeal synovial sarcoma: case report and literature review.
AB  - Synovial sarcoma is a rare malignant mesenchymal neoplasm of youth with no benign
      counterpart. This cancer typically occurs about the knee and ankle joints. The
      involvement of the head and neck region is rare, and the laryngeal location is
      exceptional, which make the correct diagnosis challenging for the surgical
      pathologist and unanticipated for the clinician. Up to our knowledge, only 14
      cases have been reported so far within this site. Here we add a new case in a 26
      year-old Saudi man who presented with voice change and dysphagia, which are
      common symptoms of a more common benign condition in this site. The patient was
      operated and the histopathological diagnosis of synovial sarcoma was made, after
      which he received radiotherapy with no recurrence after 20 months. The correct
      diagnosis is crucial in such a case for proper management.

PMID- 21177208
TI  - Breast conservative surgery for operable invasive ductal carcinoma after
      neoadjuvant chemotherapy or hormonal therapy- a challenge for breast surgeon: a
      review based on literature and experience.
AB  - Neoadjuvant chemotherapy or hormonal therapy is based on biological data and
      enables more patients to be treated with breast conserving surgery for locally
      advanced T2 and T3 without significantly increasing the rates of ipsilateral
      breast recurrence. Careful consideration of an optimal preoperative planning aims
      at accurately determining the patterns of primary tumour down staging and at the
      amount and location of any residual tumour in the breast, besides converting
      patients from mutilating surgery candidates to candidates for breast conservative
      procedure. The use of induction chemotherapy has the potential to improve the
      cosmetic results but free margins must be achieved and surgery must be planned in
      onco-plastic surgery. Axillary lymph node clearance is still the gold standard
      surgery in the treatment of the axilla. Sentinel lymph node biopsy can be done
      for clinically N0 patients but only in control trials. KEYWORDS: Neoadjuvant
      systemic therapy, breast cancer surgery.

PMID- 21177210
TI  - Gastrointestinal stromal tumours (GISTs): case report and review of the
      literature.
AB  - Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of
      the gastrointestinal tract, the majority of which is KIT (CD117) positive. In
      this case report, we describe a case of recurrent and metastatic GIST who
      presented with hepatic and brain metastases. Despite the patient's GISTs was
      negative for c-Kit (CD 117), he responded to imatinib mesylate (Glivec) treatment
      with complete resolution of his liver and brain lesions. The patient has been and
      still in complete remission for 18 months of follow-up.

PMID- 21177211
TI  - Extensive visceral calcification demonstrated on Tc-99m MDP bone scan in patient
      with sphenoidal sinus carcinoma and hypercalcaemia of malignancy: a bad
      prognostic sign.
AB  - Sphenoidal sinus carcinoma is a rare cause of hypercalcemia of malignancy. We
      report on a 37-year-old male with sphenoidal sinus carcinoma with intracranial
      extension who developed hypercalcemia of malignancy with progressing disease and
      demonstrated diffuse metastatic visceral calcifications of lungs, myocardium,
      stomach, kidneys and thyroid on follow-up 99mTc-methylene diphosphonate bone
      scan. In the absence of extensive skeletal metastases, bone scan help confirm
      humoral nature of hypercalcaeimia.

PMID- 21177212
TI  - Trichoadenoma in a mature cystic teratoma: a rare finding.
AB  - Skin adnexal tumors arising in dermoid cysts of the ovary are exceedingly rare.
      We report a trichoadenoma arising in a dermoid cyst in a 42-year-old female. The
      histopathology of trichoadenoma has also been described briefly. Mature
      teratomas, which are almost all cystic (dermoid cysts), account for approximately
      25% of all ovarian tumors, and 30% of benign ovarian tumors. They usually develop
      in children or women of the reproductive age group. Histologically, they are
      composed of variable proportions of tissue originating from the ectoderm,
      mesoderm, and endoderm. Cystic cavities are lined by mature epidermis. Although
      skin appendages and neural tissue are extremely common, there are only few case
      reports of skin adnexal tumors arising in a mature teratoma. We report a case of
      ovarian teratoma with a trichoadenoma. To the best of the authors' knowledge,
      this is the first report describing this rare benign skin adnexal tumor, in a
      mature cystic teratoma of the ovary.

PMID- 21177213
TI  - Bilateral ductal carcinoma in situ (DCIS) in a male breast: a case report.
AB  - OBJECTIVES: This case is presented to emphasize the importance of recognizing
      nipple discharge as a clinical sign of male ductal carcinoma in situ and an
      opportunity for early diagnosis. CLINICAL PRESENTATION AND INTERVENTION: A 68
      years old gentleman presented with bilateral bloody nipple discharge. Clinical
      examination of breasts showed no masses in either breasts and no axillary
      lymphadenopathy. He was investigated with bilateral mammogram, ultrasound scan
      and magnetic resonance imaging of the breasts. All were leading to a diagnosis of
      intraductal papilloma on the left retroareolar region and suspicious
      microcalcifications on the right retroareolar area. Retroareolar excision under
      general anesthesia confirmed the presence of DCIS in both specimens. Completion
      mastectomy was performed which showed no residual disease in either breasts.
      CONCLUSION: DCIS in male breast is very rare and hard to diagnose due to male
      breast morphology. It is best treated with mastectomy without axillary
      dissection.

PMID- 21177214
TI  - Soft tissue high grade myoepithelial carcinoma with round cell morphology: report
      of a newly described entity with EWSR1 gene rearrangement.
AB  - The case of soft tissue malignant myoepithelioma is presented including
      clinicopathological, immunohistochemical and cytogenetic findings. A 36-year-old
      Saudi male patient suffered from large mass involving right scapula and right
      shoulder joint measuring 14x13x11 mm. Core biopsy revealed sheets and lobules of
      poorly differentiated small malignant cells with marked atypia and frequent
      mitosis. Initially, immunohistochemistry was reactive for vimentin, pan
      cytokeratin, EMA and CD99. The case was negative for desmin, SMA, CD34, S-100
      protein and GFAP. FISH analysis exhibited negativity for SS18 (18q11.2) gene
      rearrangement and positivity for EWSR1 (22q12) gene rearrangement and a diagnosis
      of Ewing/PNET was considered. Clinical behavior and therapeutic response did not
      match the diagnosis with re-evaluation. Wedge biopsy demonstrated aggregates of
      epithelioid cells besides calponin and P63 positivity. Final diagnosis of
      malignant myoepithelioma with EWSR1 gene rearrangement was issued; a new entity
      with aggressive course. Myoepithelial carcinoma of soft tissue exhibits a wide
      spectrum of cytomorphology with overlapping phenotype similar to other soft
      tissue sarcoma like synovial sarcoma, mesenchymal chondrosarcoma, epithelioid
      sarcoma as well as Ewing/PNET. Moreover, a new finding of EWSR1 gene
      rearrangement is recognized in malignant myoepithelioma with different fusion
      partners. Hence, myoepithelial carcinoma should be kept in mind in diagnosis of
      soft tissue tumors even with unusual phenotype and gene rearrangement.

PMID- 21177215
TI  - Hepatoid adenocarcinoma of the stomach - a rare pathological entity.
AB  - Hepatoid adenocarcinoma is a rare cancer with an extremely poor prognosis. Here,
      we describe two cases referred to our hospital with suspected gastric cancer.
      Gastrointestinal endoscopy revealed lesions in the stomach. Biopsy from the
      lesions was reported as adenocarcinoma. Both the patients underwent exploratory
      laparotomy. One was an operable lesion and the other was an inoperable lesion.
      Total gastrectomy was done in the operable lesion and feeding jejunostomy was
      done in the inoperable case. Histologically, both turned out to be hepatoid
      adenocarcinomas. Retrospective analysis showed the serum levels of
      alphafetoprotein (AFP) are markedly elevated in both cases. We describe this rare
      entity of hepatoid adenocarcinoma of the stomach, and review the literature
      concerning the clinicopathological aspects of the cases.

PMID- 21177216
TI  - The need for convergence between the synergic disciplines that make up a
      resilient community.

PMID- 21177217
TI  - Business continuity strategies for cyber defence: battling time and information
      overload.
AB  - Can the same numbers and letters which are the life blood of modern business and
      government computer systems be harnessed to protect computers from attack against
      known information security risks? For the past seven years, Foreign Service
      officers and technicians of the US Government have sought to maintain diplomatic
      operations in the face of rising cyber attacks and test the hypothesis that an
      ounce of prevention is worth a pound of cure. As eight out of ten attacks
      leverage known computer security vulnerabilities or configuration setting
      weaknesses, a pound of cure would seem to be easy to come by. Yet modern security
      tools present an unusually consequential threat to business continuity - too much
      rather than too little information on cyber problems is presented, harking back
      to a phenomenon cited by social scientists in the 1960s called 'information
      overload'. Experience indicates that the longer the most serious cyber problems
      go untreated, the wider the attack surface adversaries can find. One technique
      used at the Department of State, called 'risk scoring', resulted in an 89 per
      cent overall reduction in measured risk over 12 months for the Department of
      State's servers and personal computers. Later refinements of risk scoring enabled
      technicians to correct unique security threats with unprecedented speed. This
      paper explores how the use of metrics, special care in presenting information to
      technicians and executives alike, as well as tactical use of organisational
      incentives can result in stronger cyber defences protecting modern organisations.

PMID- 21177218
TI  - Using community partners to deliver low-cost and effective emergency management
      and business continuity services.
AB  - Small to medium-sized organisations enhance their business mission as well as
      their communities by continuing to offer services in extreme circumstances.
      Developing emergency preparedness and business continuity plans that are cost
      effective, comprehensive and operational for small to medium-sized organisations
      with limited resources requires a consistent, supportive, hands-on approach over
      time with professionals to create appropriate and sustainable strategies. Using a
      unique, multi-layered and applied approach to emergency preparedness training,
      organisations have successfully created plans that are effective and sustainable.

PMID- 21177219
TI  - Mitigating risks by integrating business continuity and security.
AB  - There has been much discussion regarding the topic of business continuity and
      security convergence. This paper provides a realistic overview of the union of
      the two disciplines and offers no/low-cost programme elements that may be used
      for organisations considering or in the midst of convergence efforts.

PMID- 21177220
TI  - The creation of regional partnerships for regional emergency planning.
AB  - Regional partnerships for regional emergency planning are relationships developed
      between disparate emergency planning stakeholders from multiple jurisdictions and
      with different missions. Regional partnerships are essential for the management
      of limited resources and for responding to large-scale disasters that can
      overwhelm local resources. Emergency response planners develop these partnerships
      as needs develop within their own jurisdictions or in response to lessons learned
      from previous disaster responses. This paper discusses a model process for
      developing or enhancing an all-hazards regional emergency planning network to
      create regional collaboration and resource allocation. This model process can be
      adapted and customised in any community to develop partnerships between
      communities, public agencies, non-governmental organisations, faith-based
      organisations and the private sector within a region. The model process and how
      to use it in communities will be discussed, including a qualitative analysis of
      its application.

PMID- 21177221
TI  - Implementing business continuity effectively within the UK National Health
      Service.
AB  - Whereas major incident planning is very well established within National Health
      Service (NHS) organisations in the UK, business continuity management (BCM)
      planning, in many cases, is a relatively new activity; however, a combination of
      factors including the emergence of H1N1 influenza, has led to growing interest in
      the subject. This paper draws on both the personal experience of the authors and
      published research in relevant fields to make a number of specific
      recommendations about the effective implementation of BCM within NHS
      organisations. These include the need to define the BCM project properly; conduct
      a thorough business impact analysis considering 'back office' as well as clinical
      activities; define suitable command and control arrangements with clear delegated
      authority; and support plan development with appropriate training.

PMID- 21177222
TI  - Creating meaningful business continuity management programme metrics.
AB  - The popular axiom, 'what gets measured gets done', is often applied in the
      quality management and continuous improvement disciplines. This truism is also
      useful to business continuity practitioners as they continually strive to prove
      the value of their organisation's investment in a business continuity management
      (BCM) programme. BCM practitioners must also remain relevant to their
      organisations as executives focus on the bottom line and maintaining stakeholder
      confidence. It seems that executives always find a way, whether in a hallway or
      elevator, to ask BCM professionals about the company's level of readiness. When
      asked, they must be ready with an informed response. The establishment of a
      process to measure business continuity programme performance and organisational
      readiness has emerged as a key component of US Department of Homeland Security
      'Voluntary Private Sector Preparedness (PS-Prep) Program' standards where the
      overarching goal is to improve private sector preparedness for disasters and
      emergencies. The purpose of this paper is two-fold: to introduce continuity
      professionals to best practices that should be considered when developing a BCM
      metrics programme as well as providing a case study of how a large health
      insurance company researched, developed and implemented a process to measure BCM
      programme performance and company readiness.

PMID- 21177223
TI  - Analysing the external supply chain risk driver competitiveness: a risk
      mitigation framework and business continuity plan.
AB  - Innovation challenges for handling supply chain risks have become one of the most
      important drivers in business competitiveness and differentiation. This study
      analyses competitiveness at the external supply chain level as a driver of risks
      and provides a framework for mitigating these risks. The mitigation framework,
      also called the supply chain continuity framework, provides insight into six
      stages of the business continuity planning (BCP) process life cycle (risk
      mitigation management, business impact analysis, supply continuity strategy
      development, supply continuity plan development, supply continuity plan testing
      and supply continuity plan maintenance), together with the operational
      constructs: customer service, inventory management, flexibility, time to market,
      ordering cycle time and quality. The purpose of the BCP process life cycle and
      operational constructs working together is to emphasise the way in which a supply
      chain can deal with disruption risks and, consequently, bring competitive
      advantage. Future research will consider the new risk scenarios and analyse the
      consequences to promote the improvement of supply chain resilience.

PMID- 21177224
TI  - Applying social science and public health methods to community-based pandemic
      planning.
AB  - Pandemic influenza is a unique threat to communities, affecting schools,
      businesses, health facilities and individuals in ways not seen in other emergency
      events. This paper aims to outline a local government project which utilised
      public health and social science research methods to facilitate the creation of
      an emergency response plan for pandemic influenza coincidental to the early
      stages of the 2009 H1N1 ('swine flu') outbreak. A multi-disciplinary team
      coordinated the creation of a pandemic influenza emergency response plan which
      utilised emergency planning structure and concepts and encompassed a diverse
      array of county entities including schools, businesses, community organisations,
      government agencies and healthcare facilities. Lessons learned from this project
      focus on the need for (1) maintaining relationships forged during the planning
      process, (2) targeted public health messaging, (3) continual evolution of
      emergency plans, (4) mutual understanding of emergency management concepts by
      business and community leaders, and (5) regional coordination with entities
      outside county boundaries.

PMID- 21177225
TI  - [Surgical challenges of chest wall and intra-thoracic desmoid tumors].
AB  - Chest wall desmoids are rare, borderline tumors. Radical surgical excision is
      considered to be the primary treatment. Tendency of desmoids to infiltrate the
      chest wall, the shoulder girdle, lung parenchyma, brachial plexus and vital
      components of the mediastinum provides a difficult surgical challenge in the
      efforts of achieving microscopically negative margins. Implantation of synthetic
      meshes and reconstructive plastic surgical techniques might be necessary to
      perform in order to preserve stability of the thorax, and to achieve optimal
      functional and aesthetic results. Multidisciplinary surgeries may result in a
      high rate of morbidity even in specialized centers. Within the framework of a
      retrospective multicenter review, authors assessed surgical techniques
      implemented in the case of patients who underwent surgical management for
      sporadically appearing chest-wall and intra-thoracic desmoids, and reviewed the
      relevant literature.

PMID- 21177226
TI  - [Postoperative surveillance of wound infection after cesarean section at Kenezy
      Hospital, Debrecen, Hungary].
AB  - Wound infection is a typical, partly preventable complication of cesarean
      sections. We started extended recording of cesarean section data in October, 2008
      as part of our general wound infection surveillance program. AIM: To describe the
      circumstances and outcomes of the sections and analyze associations between them.
      METHODS: We analyzed 523 cases over the period October 1, 2008 to September 30,
      2009. Variables were assessed using descriptive statistics. Associations between
      explanatory factors and wound infection were evaluated using logistic regression.
      RESULTS: Infections (overall rate: 3.6%) were more frequent in younger subjects,
      those with anemia, subcutaneous hematoma, in pregnancies with meconium stained or
      purulent amniotic fluid, and decreased to about a third after infection control
      was tightened. CONCLUSIONS: by being a proxy variable of factors with which wound
      infection is associated, age is a clinically valuable predictive variable. Good
      infection control practice is effective in preventing wound infections. The
      results are consistent with appropriate prescription practices of prophylactic
      antibiotic use, and with prophylactic measures being effective.

PMID- 21177227
TI  - [Heart transplantation after corrective surgery of a congenital heart disease.
      Surgical technical problems].
AB  - Heart transplantation was performed in a 17-year old boy with severe left
      ventricular failure. Previously a congenital heart disease, tetralogy of Fallot
      was reconstructed in one and half years old of age. Authors present the different
      surgical problems complicated this procedure. In Hungary this is the first heart
      transplantation after a corrective surgical procedure of a complex congenital
      heart disease.

PMID- 21177228
TI  - [Innovative education: simulation-based training at the Institute of Health
      Sciences, Semmelweis University, Hungary].
AB  - In Hungary, the Institute of Health Sciences at Semmelweis University was the
      first institution to introduce patient simulation-based practical training of non
      physician professionals. Before introducing this novel educational methodology,
      students could only practice particular examinations and interventions on
      demonstration tools. Using the simulator they can also follow and analyze the
      effects of the interventions that have been made. The high fidelity, adult Human
      Patients Emergency Care Simulator (HPS-ECS, Medical Education Technologies
      Incorporation, Sarasota, Florida, USA) is particularly suitable for acquiring
      skills related to the management of various emergency situations. The 180 cm and
      34 kg mannequin which can operate in lying and sitting positions has both
      respiration and circulation which can be examined the same way as in a living
      person. It is capable to produce several physical and clinical signs such as
      respiration with chest movement, electric cardiac activity, palpable pulse, and
      measurable blood pressure. In addition, it can also exhibit blinking, swelling of
      the tongue and whole-body trembling while intestinal, cardiac and pulmonary
      sounds can equally be examined. The high fidelity simulator allows various
      interventions including monitoring, oxygen therapy, bladder catheterization,
      gastric tube insertion, injection, infusion and transfusion therapy to be
      practiced as part of complex patient management. Diagnostic instruments such as
      ECG recorder, sphygmomanometer, pulse-oxymeter can be attached to the simulator
      which can also respond to different medical interventions such as intubation,
      defibrillation, pacing, liquid supplementing, and blood transfusion. The
      mannequin's physiological response can be followed up and monitored over time to
      assess whether the selected intervention has been proven adequate to achieve the
      desired outcome. Authors provide a short overview of the possible applications of
      clinical simulation for education and training in health sciences, and present
      how patient simulator has been embedded in various practical courses as part of
      different curriculum designed for different health care specialties.

PMID- 21177231
TI  - [Office hysteroscopy: a new examination method in gynecological practice].
AB  - Hysteroscopy is a widely used endoscopic method, the "gold standard" for the
      examination of uterine cavity changes. Office hysteroscopy is an intervention
      that makes the accomplishment of ambulant examination, opposite to the
      traditional method. Due to the small diameter of the device the anesthesia is
      unnecessary, because there is no need of the dilatation of the cervix.
      Indications of the examination are wide-ranging. Besides the abnormal uterine
      bleeding, it can be used in the examination of infertility, and those
      intrauterine changes (polyp, submucosus myoma, adhesion), that were diagnosed by
      other imagining methods that cause infertility complaints. The aim of our present
      review is recommend the use of this method because it does not need any
      preparation and it is minimal invasive. The use of traditional method that needs
      longer preparation, observation, anesthesia and operating theatre, is only
      suggested in cases of proven pathology.

PMID- 21177230
TI  - [First detection of human astrovirus in gastroenteritis outbreak in Hungary].
AB  - Human astroviruses are one of the known pathogens of gastroenteritis in infants,
      children and rarely in elderly. It causes 4.2-7.3% of the sporadic
      gastroenteritis cases with diarrhea and vomiting in children. The etiological
      role of astrovirus has not been confirmed yet in outbreaks of gastroenteritis in
      Hungary. AIMS: The first description of the detection and molecular epidemiology
      of astrovirus in outbreaks of gastroenteritis in Hungary. MATERIALS AND METHODS:
      Stool samples originated from Komarom-Esztergom County, from a day-care center
      (nursery) where a gastroenteritis outbreak occurred in June, 2010. Astrovirus was
      detected by RT-PCR methods. The nucleotide sequence of the nearly complete genome
      was sequenced. Clinical and epidemiological data were collected by
      epidemiological investigation. RESULTS: Out of the 29 exposed persons (24
      children and 5 adults) 7 (24.1%) children had gastroenteritis with diarrhea, and
      vomiting in one case, in the period of June 4-15, 2010. Bacterial pathogens,
      rotavirus, adenovirus and norovirus were not detected, but genotype 1 astrovirus
      could be identified in 3 (42.8%) stool samples (HQ398856). The nucleotide
      sequence of the astrovirus ORF1a/ORF1b/ORF2/3'UTR regions was determined. The
      source of the outbreak was presumably the firstly recognized ill child and the
      virus was spread by fecal-oral route with direct contact in the children
      community. CONCLUSIONS: Epidemiologic and clinical characteristics of the
      astrovirus outbreak in the nursery are described in details to prove that the
      possible etiological role of astroviruses in viral gastroenteritis which should
      not forget in order after rotaviruses, caliciviruses (norovirus and sapovirus)
      and enteric adenoviruses.

PMID- 21177232
TI  - [Next generation sequencing technologies (NGST) -- development and applications].
AB  - In the past ten years the development of next generation sequencing technologies
      brought a new era in the field of quick and efficient DNA sequencing. In our
      study we give an overview of the methodological achievements from Sanger's chain
      termination sequencing in 1975 to those allowing real-time DNA sequencing today.
      Sequencing methods that utilize clonal amplicons for parallel multistrand
      sequencing comprise the basics of currently available next generation sequencing
      techniques. Nowadays next generation sequencing is mainly used for basic research
      in functional genomics, providing quintessential information in the meta-analyses
      of data from signal transduction pathways, onthologies, proteomics and
      metabolomics. Although next generation sequencing is yet sparsely used in
      clinical practice, cardiology, oncology and epidemiology already show an immense
      need for the additional knowledge obtained by this new technology. The main
      barrier of its spread is the lack of standardization of analysis evaluation
      methods, which obscure objective assessment of the results.

PMID- 21177233
TI  - [Subcutaneous immunoglobulin substitution and therapy].
AB  - Patients with combined primary immunodeficiency or B-cell deficiency with low
      serum concentration of immunoglobulin G can be efficiently treated with
      immunoglobulin G concentrates. From the 1950s IgG was used intramuscularly, and
      from the 1980s intravenous immunoglobulin (IVIG) replacement has become widely
      available for replacement therapy. Among the potential side effects of IVIG
      (including anaphylaxis), further disadvantages of IVIG are hospitalization during
      treatment and varying concentrations of IgG. Over the past ten years,
      subcutaneous IgG (SCIG) preparations have become reasonable alternatives to IVIG.
      SCIG given weekly assures a more balanced serum IgG level, side affects are
      mostly local and temporary; systemic, severe adverse events have not been
      observed. In addition, SCIG can be used for home treatment of patients which
      improves their quality of life remarkably.

PMID- 21177234
TI  - [The Hungarian chapter of the story of digitalis].

PMID- 21177235
TI  - [The history of the fig tree (Ficus carica L.) and its use in phytotherapy].

PMID- 21177236
TI  - [Repeated slandering against Prof. Dr. Aladar Kettesy in 1945-46].

PMID- 21177239
TI  - The parahippocampal gyrus as a neural marker of early remission in first-episode
      psychosis: a voxel-based morphometry study.
AB  - INTRODUCTION: Outcome from psychotic disorders is heterogeneous with poor long
      term clinical outcome associated with such markers as decreased internal capsule
      volume and increased ventricular volumes. No previous study has examined
      neuroimaging markers in relation to early remission. METHODS: This neuroimaging
      study included 68 previously untreated first episode of psychosis (FEP) patients,
      of whom 28 achieved remission and 40 did not after six months of treatment, and
      42 healthy controls. Using voxel-based morphometry (VBM), we set out to determine
      if specific neural correlates could be identified in FEP patients not achieving
      remission in a specialized early-intervention service. RESULTS: Nonremitted
      patients had significant lower grey matter concentration (GMC) in the
      parahippocampal gyrus bilaterally compared to remitted patients. A classification
      model utilizing parahippocampal GMC correctly classified remission status 79% of
      the time and accounted for 56% of the variance. Moreover, GMC on the left (r=
      0.35, p=0.004) and right (r=-0.47, p<0.0001) side correlated with social
      withdrawal while only the left side correlated with verbal memory (r=0.21,
      p=0.03). CONCLUSIONS: Neural markers of early remission are present in first
      episode patients. A better understanding of the neural etiology of psychosis and
      its relationship to outcome may encourage the search for new medications to help
      improve outcome in relation to the identified brain regions like the
      parahippocampal gyrus.

PMID- 21177240
TI  - Trajectories of social withdrawal and cognitive decline in the schizophrenia
      prodrome.
AB  - OBJECTIVE: Schizophrenia is a heterogeneous neurodevelopmental disorder. Patients
      with high levels of negative symptoms have been identified as a specific subtype,
      but little is known about how the neurodevelopmental course may differ in this
      group. This study aimed to characterize developmental trajectories of premorbid
      social withdrawal and cognitive decline between patients with high versus low
      levels of negative symptoms in youth with schizophrenia-spectrum disorders.
      METHOD: A standardized timeline was used to delineate the emergence of psychosis,
      social withdrawal, and cognitive decline in 52 subjects aged 8 to 19 with
      schizophrenia (n=36), schizophreniform (n=6), or schizoaffective disorder (n=10).
      The sample was divided into subgroups of high- (n=26) versus low- (n=26) negative
      symptoms, and developmental trajectories of premorbid symptoms were compared
      between groups. RESULTS: Mean ages for emergence of social withdrawal, cognitive
      decline, and psychosis were 11.1 years (SD=2.5), 11.9 (SD=4.4) and 13.2 years
      (SD=1.2), respectively. In the high-negative symptom group, the premorbid
      developmental trajectory for social withdrawal was more protracted. This group
      also had more severe cognitive decline at the onset of psychosis, but the
      premorbid trajectories for cognitive decline did not differ significantly between
      groups. CONCLUSIONS: This work documents a more severe and protracted trajectory
      of premorbid social withdrawal in patients with high levels of negative symptoms
      in comparison to those with low-negative symptoms. The findings reported here are
      supportive of the hypothesis that patients with illness characterized by high
      levels of negative symptoms may represent a subgroup with distinct
      neurodevelopmental abnormalities.

PMID- 21177243
TI  - Differentiating psychosis versus fluent aphasia.
AB  - Following a stroke, a patient may present with varying degrees of neurological
      impairment, depending on the area of the brain which is damaged. Specifically,
      damage to the left cortical hemisphere may result in aphasia. The characteristic
      speech in a patient with an aphasia caused by a stroke can be similar to the
      speech in some patients with schizophrenia or other psychotic disorders. In a new
      patient without a reliable history who presents with suspected aphasia, it is
      important to include psychotic disorders as part of the differential diagnosis.
      Failure to differentiate psychotic disorders from aphasia could result in either
      a lack of treatment that would improve the patient's thought process, thought
      content, or language, or in a delayed treatment for a stroke, respectively. While
      a number of psychotic disorders exist and must be differentiated from one another
      in accordance with DSM-IV guidelines, speech abnormalities in patients with
      schizophrenia are well described in the literature. For this reason,
      schizophrenia is the psychotic disorder of focus in this paper. This case report
      illustrates a clinical situation where a patient required both a psychiatric and
      neurological consultation in order to determine the etiology of his language
      disorder. The purpose of this paper is to emphasize the need to consider both
      psychiatric disorders and aphasia in patients with unknown histories who present
      with language abnormalities, and to help the clinician critically examine the
      patient's speech so that, in conjunction with other clinical data, the correct
      diagnosis can be made and appropriate treatment initiated.

PMID- 21177242
TI  - Lurasidone for schizophrenia: a brief review of a new second-generation
      antipsychotic.
AB  - Lurasidone is a second-generation antipsychotic newly approved by the U.S. Food
      and Drug Administration for the treatment of schizophrenia. Similar to most other
      second-generation antipsychotics, lurasidone is a full antagonist at dopamine D2
      and serotonin 5HT2A receptors. Efficacy within the dose range of 40-120 mg/d was
      established in four 6-week, randomized, controlled trials. The recommended
      starting dose is 40 mg/d and the maximum recommended dose is 80 mg/d. Doses above
      80 mg/d do not appear to confer added benefit and may be associated with a dose
      related increase in certain adverse reactions such as somnolence and akathisia.
      Lurasidone is administered once daily with at least 350 calories of food in order
      to optimize bioavailability. Lurasidone is primarily metabolized in the liver
      through the CYP3A4 enzyme system, and coadministration with drugs that are strong
      inhibitors of CYP3A4 (such as ketoconazole) or strong inducers (such as rifampin)
      are contraindicated. Lurasidone is associated with minimal weight gain and no
      clinically meaningful alterations in glucose, lipids, or the ECG QT interval.

PMID- 21177241
TI  - Elderly patients with schizophrenia and depression: diagnosis and treatment.
AB  - BACKGROUND: The treatment of older patients with schizophrenia and depressive
      symptoms poses many challenges for clinicians. Current classifications of
      depressive symptoms in patients with schizophrenia include: Major Depressive
      Episodes that occur in patients with schizophrenia and are not classified as
      schizoaffective disorder, Schizoaffective Disorder, and Schizophrenia with
      subsyndromal depression in which depressive symptoms do not meet criteria for
      Major Depression. Research indicates that the presence of any of these depressive
      symptoms negatively impacts the lives of patients suffering from schizophrenia
      spectrum disorders. PURPOSE: The purpose of this paper is to review the
      literature related to older patients with schizophrenia-spectrum disorders and co
      occurring depressive symptoms, and to guide mental health professionals to better
      understand the diagnosis and treatment of depressive symptoms in patients with
      schizophrenia. CONCLUSIONS: The treatment of elderly patients with schizophrenia
      and depressive symptoms includes first reassessing the diagnosis to make sure
      symptoms are not due to a comorbid condition, metabolic problems or medications.
      If these are ruled out, pharmacological agents in combination with psychosocial
      interventions are important treatments for older patients with schizophrenia and
      depressive symptoms. A careful assessment of each patient is needed in order to
      determine which antipsychotic would be optimal for their care; second-generation
      antipsychotics are the most commonly used antipsychotics. Augmentation with an
      antidepressant medication can be helpful for the elderly patient with
      schizophrenia and depressive symptoms. More research with pharmacologic and
      psychosocial interventions is needed, however, to better understand how to treat
      this population of elderly patients.

PMID- 21177244
TI  - Expression and function of human MRP1 (ABCC1) is dependent on amino acids in
      cytoplasmic loop 5 and its interface with nucleotide binding domain 2.
AB  - Multidrug resistance protein 1 (MRP1) is an ATP-binding cassette transporter that
      effluxes drugs and organic anions across the plasma membrane. The 17
      transmembrane helices of MRP1 are linked by extracellular and cytoplasmic loops
      (CLs), but their role in coupling the ATPase activity of MRP1 to the
      translocation of its substrates is poorly understood. Here we have examined the
      importance of CL5 by mutating eight conserved charged residues and the helix
      disrupting Gly(511) in this region. Ala substitution of Lys(513), Lys(516),
      Glu(521), and Glu(535) markedly reduced MRP1 levels. Because three of these
      residues are predicted to lie at the interface of CL5 and the second nucleotide
      binding domain (NBD2), a critical role is indicated for this region in the plasma
      membrane expression of MRP1. Further support for this idea was obtained by
      mutating NBD2 amino acids His(1364) and Arg(1367) at the CL5 interface, which
      also resulted in reduced MRP1 levels. In contrast, mutation of Arg(501),
      Lys(503), Glu(507), Arg(532), and Gly(511) had no effect on MRP1 levels. Except
      for K503A, however, transport by these mutants was reduced by 50 to 75%, an
      effect largely attributable to reduced substrate binding and affinity. Studies
      with (32)P-labeled azido-ATP also indicated that whereas ATP binding by the G511I
      mutant was unchanged, vanadate-induced trapping of azido-ADP was reduced,
      indicating changes in the catalytic activity of MRP1. Together, these data
      demonstrate the multiple roles for CL5 in the membrane expression and function of
      MRP1.

PMID- 21177245
TI  - Eukaryotic lagging strand DNA replication employs a multi-pathway mechanism that
      protects genome integrity.
AB  - In eukaryotic nuclear DNA replication, one strand of DNA is synthesized
      continuously, but the other is made as Okazaki fragments that are later joined.
      Discontinuous synthesis is inherently more complex, and fragmented intermediates
      create risks for disruptions of genome integrity. Genetic analyses and
      biochemical reconstitutions indicate that several parallel pathways evolved to
      ensure that the fragments are made and joined with integrity. An RNA primer is
      removed from each fragment before joining by a process involving polymerase
      dependent displacement into a single-stranded flap. Evidence in vitro suggests
      that, with most fragments, short flaps are displaced and efficiently cleaved.
      Some flaps can become long, but these are also removed to allow joining. Rarely,
      a flap can form structure, necessitating displacement of the entire fragment.
      There is now evidence that post-translational protein modification regulates the
      flow through the pathways to favor protection of genomic information in regions
      of actively transcribed chromatin.

PMID- 21177246
TI  - Differential G-protein-coupled receptor phosphorylation provides evidence for a
      signaling bar code.
AB  - G-protein-coupled receptors are hyper-phosphorylated in a process that controls
      receptor coupling to downstream signaling pathways. The pattern of receptor
      phosphorylation has been proposed to generate a "bar code" that can be varied in
      a tissue-specific manner to direct physiologically relevant receptor signaling.
      If such a mechanism existed, receptors would be expected to be phosphorylated in
      a cell/tissue-specific manner. Using tryptic phosphopeptide maps, mass
      spectrometry, and phospho-specific antibodies, it was determined here that the
      prototypical G(q/11)-coupled M(3)-muscarinic receptor was indeed differentially
      phosphorylated in various cell and tissue types supporting a role for
      differential receptor phosphorylation in directing tissue-specific signaling.
      Furthermore, the phosphorylation profile of the M(3)-muscarinic receptor was also
      dependent on the stimulus. Full and partial agonists to the M(3)-muscarinic
      receptor were observed to direct phosphorylation preferentially to specific
      sites. This hitherto unappreciated property of ligands raises the possibility
      that one mechanism underlying ligand bias/functional selectivity, a process where
      ligands direct receptors to preferred signaling pathways, may be centered on the
      capacity of ligands to promote receptor phosphorylation at specific sites.

PMID- 21177247
TI  - Glycoside hydrolase family 89 alpha-N-acetylglucosaminidase from Clostridium
      perfringens specifically acts on GlcNAc alpha1,4Gal beta1R at the non-reducing
      terminus of O-glycans in gastric mucin.
AB  - In mammals, alpha-linked GlcNAc is primarily found in heparan sulfate/heparin and
      gastric gland mucous cell type mucin. alpha-N-acetylglucosaminidases
      (alphaGNases) belonging to glycoside hydrolase family 89 are widely distributed
      from bacteria to higher eukaryotes. Human lysosomal alphaGNase is well known to
      degrade heparin and heparan sulfate. Here, we reveal the substrate specificity of
      alphaGNase (AgnC) from Clostridium perfringens strain 13, a bacterial homolog of
      human alphaGNase, by chemically synthesizing a series of disaccharide substrates
      containing alpha-linked GlcNAc. AgnC was found to release GlcNAc from
      GlcNAcalpha1,4Galbeta1pMP and GlcNAcalpha1pNP substrates (where pMP and pNP
      represent p-methoxyphenyl and p-nitrophenyl, respectively). AgnC also released
      GlcNAc from porcine gastric mucin and cell surface mucin. Because AgnC showed no
      activity against any of the GlcNAcalpha1,2Galbeta1pMP, GlcNAcalpha1,3Galbeta1pMP,
      GlcNAcalpha1,6Galbeta1pMP, and GlcNAcalpha1,4GlcAbeta1pMP substrates, this enzyme
      may represent a specific glycosidase required for degrading alpha-GlcNAc-capped O
      glycans of the class III mucin secreted from the stomach and duodenum. Deletion
      of the C-terminal region containing several carbohydrate-binding module 32
      (CBM32) domains significantly reduced the activity for porcine gastric mucin;
      however, activity against GlcNAcalpha1,4Galbeta1pMP was markedly enhanced. Dot
      blot and ELISA analyses revealed that the deletion construct containing the C
      terminal CBM-C2 to CBM-C6 domains binds strongly to porcine gastric mucin.
      Consequently, tandem CBM32 domains located near the C terminus of AgnC should
      function by increasing the affinity for branched or clustered alpha-GlcNAc
      containing glycans. The agnC gene-disrupted strain showed significantly reduced
      growth on the class III mucin-containing medium compared with the wild type
      strain, suggesting that AgnC might have an important role in dominant growth in
      intestines.

PMID- 21177248
TI  - Lipoprotein lipase is a novel amyloid beta (Abeta)-binding protein that promotes
      glycosaminoglycan-dependent cellular uptake of Abeta in astrocytes.
AB  - Lipoprotein lipase (LPL) is a member of a lipase family known to hydrolyze
      triglyceride molecules in plasma lipoprotein particles. LPL also plays a role in
      the binding of lipoprotein particles to cell-surface molecules, including
      sulfated glycosaminoglycans (GAGs). LPL is predominantly expressed in adipose and
      muscle but is also highly expressed in the brain where its specific roles are
      unknown. It has been shown that LPL is colocalized with senile plaques in
      Alzheimer disease (AD) brains, and its mutations are associated with the severity
      of AD pathophysiological features. In this study, we identified a novel function
      of LPL; that is, LPL binds to amyloid beta protein (Abeta) and promotes cell
      surface association and uptake of Abeta in mouse primary astrocytes. The
      internalized Abeta was degraded within 12 h, mainly in a lysosomal pathway. We
      also found that sulfated GAGs were involved in the LPL-mediated cellular uptake
      of Abeta. Apolipoprotein E was dispensable in the LPL-mediated uptake of Abeta.
      Our findings indicate that LPL is a novel Abeta-binding protein promoting
      cellular uptake and subsequent degradation of Abeta.

PMID- 21177249
TI  - A new cytosolic pathway from a Parkinson disease-associated kinase, BRPK/PINK1:
      activation of AKT via mTORC2.
AB  - Accumulating evidence indicates that dysfunction of mitochondria is a common
      feature of Parkinson disease. Functional loss of a familial Parkinson disease
      linked gene, BRPK/PINK1 (PINK1), results in deterioration of mitochondrial
      functions and eventual neuronal cell death. A mitochondrial chaperone protein has
      been shown to be a substrate of PINK1 kinase activity. In this study, we
      demonstrated that PINK1 has another action point in the cytoplasm.
      Phosphorylation of Akt at Ser-473 was enhanced by overexpression of PINK1, and
      the Akt activation was crucial for protection of SH-SY5Y cells from various
      cytotoxic agents, including oxidative stress. Enhanced Akt phosphorylation was
      not due to activation of phosphatidylinositol 3-kinase but due to activation of
      mammalian target of rapamycin complex 2 (mTORC2) by PINK1. Rictor, a specific
      component of mTORC2, was phosphorylated by overexpression of PINK1. Furthermore,
      overexpression of PINK1 enhanced cell motility. These results indicate that PINK1
      exerts its cytoprotective function not only in mitochondria but also in the
      cytoplasm through activation of mTORC2.

PMID- 21177250
TI  - HDAC3-dependent reversible lysine acetylation of cardiac myosin heavy chain
      isoforms modulates their enzymatic and motor activity.
AB  - Reversible lysine acetylation is a widespread post-translational modification
      controlling the activity of proteins in different subcellular compartments. We
      previously demonstrated that a class II histone deacetylase (HDAC), HDAC4, and a
      histone acetyltransferase, PCAF, associate with cardiac sarcomeres, and a class I
      and II HDAC inhibitor, trichostatin A, enhances contractile activity of
      myofilaments. In this study, we show that a class I HDAC, HDAC3, is also present
      at cardiac sarcomeres. By immunohistochemical and electron microscopic analyses,
      we found that HDAC3 was localized to the A band of sarcomeres and was capable of
      deacetylating myosin heavy chain (MHC) isoforms. The motor domains of both
      cardiac alpha- and beta-MHC isoforms were found to be reversibly acetylated.
      Biomechanical studies revealed that lysine acetylation significantly decreased
      the K(m) for the actin-activated ATPase activity of both alpha- and beta-MHC
      isoforms. By an in vitro motility assay, we found that lysine acetylation
      increased the actin sliding velocity of alpha-myosin by 20% and beta-myosin by
      36%, compared to their respective non-acetylated isoforms. Moreover, myosin
      acetylation was found to be sensitive to cardiac stress. During induction of
      hypertrophy, myosin isoform acetylation increased progressively with duration of
      stress stimuli, independent of isoform shift, suggesting that lysine acetylation
      of myosin could be an early response of myofilaments to increase contractile
      performance of the heart. These studies provide the first evidence for
      localization of HDAC3 at myofilaments and uncover a novel mechanism modulating
      the motor activity of cardiac MHC isoforms.

PMID- 21177251
TI  - The role of monoubiquitination in endocytic degradation of human ether-a-go-go
      related gene (hERG) channels under low K+ conditions.
AB  - A reduction in extracellular K(+) concentration ([K(+)](o)) causes cardiac
      arrhythmias and triggers internalization of the cardiac rapidly activating
      delayed rectifier potassium channel (I(Kr)) encoded by the human ether-a-go-go
      related gene (hERG). We investigated the role of ubiquitin (Ub) in endocytic
      degradation of hERG channels stably expressed in HEK cells. Under low K(+)
      conditions, UbKO, a lysine-less mutant Ub that only supports monoubiquitination,
      preferentially interacted and selectively enhanced degradation of the mature hERG
      channels. Overexpression of Vps24 protein, also known as charged multivesicular
      body protein 3, significantly accelerated degradation of mature hERG channels,
      whereas knockdown of Vps24 impeded this process. Moreover, the lysosomal
      inhibitor bafilomycin A1 inhibited degradation of the internalized mature hERG
      channels. Thus, monoubiquitination directs mature hERG channels to degrade
      through the multivesicular body/lysosome pathway. Interestingly, the protease
      inhibitor lactacystin inhibited the low K(+)-induced hERG endocytosis and
      concomitantly led to an accumulation of monoubiquitinated mature hERG channels,
      suggesting that deubiquitination is also required for the endocytic degradation.
      Consistently, overexpression of the endosomal deubiquitinating enzyme signal
      transducing adaptor molecule-binding protein significantly accelerated whereas
      knockdown of endogenous signal transducing adaptor molecule-binding protein
      impeded degradation of the mature hERG channels under low K(+) conditions. Thus,
      monoubiquitin dynamically mediates endocytic degradation of mature hERG channels
      under low K(+) conditions.

PMID- 21177252
TI  - Manganese uptake and distribution in the brain after methyl bromide-induced
      lesions in the olfactory epithelia.
AB  - Manganese (Mn) is an essential nutrient with potential neurotoxic effects. Mn
      deposited in the nose is apparently transported to the brain through anterograde
      axonal transport, bypassing the blood-brain barrier. However, the role of the
      olfactory epithelial cells in Mn transport from the nasal cavity to the blood and
      brain is not well understood. We utilized the methyl bromide (MeBr) lesion model
      wherein the olfactory epithelium fully regenerates in a time-dependent and cell
      type-specific manner over the course of 6-8 weeks postinjury. We instilled
      (54)MnCl(2) intranasally at different recovery periods to study the role of
      specific olfactory epithelial cell types in Mn transport. (54)MnCl(2) was
      instilled at 2, 4, 7, 21, and 56 days post-MeBr treatment. (54)Mn concentrations
      in the blood were measured over the first 4-h period and in the brain and other
      tissues at 7 days postinstillation. Age-matched control rats were similarly
      studied at 2 and 56 days. Blood and tissue (54)Mn levels were reduced initially
      but returned to control values by day 7 post-MeBr exposure, coinciding with the
      reestablishment of sustentacular cells. Brain (54)Mn levels also decreased but
      returned to control levels only by 21 days, the period near the completion of
      neuronal regeneration/bulbar reinnervation. Our data show that Mn transport to
      the blood and brain temporally correlated with olfactory epithelial regeneration
      post-MeBr injury. We conclude that (1) sustentacular cells are necessary for Mn
      transport to the blood and (2) intact axonal projections are required for Mn
      transport from the nasal cavity to the olfactory bulb and brain.

PMID- 21177253
TI  - Dipentyl phthalate dosing during sexual differentiation disrupts fetal testis
      function and postnatal development of the male Sprague-Dawley rat with greater
      relative potency than other phthalates.
AB  - Phthalate esters (PEs) constitute a large class of plasticizer compounds that are
      widely used for many consumer product applications. Ten or more members of the PE
      class of compounds are known to induce male fetal endocrine toxicity and
      postnatal reproductive malformations by disrupting androgen production during the
      sexual differentiation period of development. An early study conducted in the rat
      pubertal model suggested that dipentyl phthalate (DPeP) may be a more potent
      testicular toxicant than some more extensively studied phthalates. Regulatory
      agencies require dose-response and potency data to facilitate risk assessment;
      however, very little data are currently available for DPeP. The goal of this
      study was to establish a more comprehensive data set for DPeP, focusing on dose
      response and potency information for fetal and postnatal male reproductive
      endpoints. We dosed pregnant rats on gestational day (GD) 17 or GD 14-18 and
      subsequently evaluated fetal testicular testosterone (T) production on GD 17.5
      and GD 18, respectively. We also dosed pregnant rats on GD 8-18 and evaluated
      early postnatal endpoints in male offspring. Comparison of these data to data
      previously obtained under similar conditions for di (2-ethylhexyl) phthalate
      indicates that DPeP is approximately eightfold more potent in reducing fetal T
      production and two- to threefold more potent in inducing development of early
      postnatal male reproductive malformations. Additionally, fetal testicular T
      production was more sensitive to inhibitory effects of DPeP exposure than was
      gene expression of target genes involved in male reproductive development,
      supporting the use of this endpoint as a critical effect in the risk assessment
      process.

PMID- 21177254
TI  - Prenatal exposure to flavonoids: implication for cancer risk.
AB  - Flavonoids are potent antioxidants, freely available as high-dose dietary
      supplements. However, they can induce DNA double-strand breaks (DSB) and
      rearrangements in the mixed-lineage leukemia (MLL) gene, which are frequently
      observed in childhood leukemia. We hypothesize that a deficient DSB repair, as a
      result of an Atm mutation, may reinforce the clastogenic effect of dietary
      flavonoids and increase the frequency of Mll rearrangements. Therefore, we
      examined the effects of in vitro and transplacental exposure to high, but
      biological amounts of flavonoids in mice with different genetic capacities for
      DSB repair (homozygous/heterozygous knock-in for human Atm mutation [Atm
      DeltaSRI] vs. wild type [wt]). In vitro exposure to genistein/quercetin induced
      higher numbers of Mll rearrangements in bone marrow cells of Atm-DeltaSRI mutant
      mice compared with wt mice. Subsequently, heterozygous Atm-DeltaSRI mice were
      placed on either a flavonoid-poor or a genistein-enriched (270 mg/kg) or
      quercetin-enriched (302 mg/kg) feed throughout pregnancy. Prenatal exposure to
      flavonoids associated with higher frequencies of Mll rearrangements and a slight
      increase in the incidence of malignancies in DNA repair-deficient mice. These
      data suggest that prenatal exposure to both genistein and quercetin supplements
      could increase the risk on Mll rearrangements especially in the presence of
      compromised DNA repair.

PMID- 21177256
TI  - MSX1 and TGF-beta3 are novel target genes functionally regulated by FOXE1.
AB  - FOXE1 mutations cause the Bamforth-Lazarus syndrome characterized by thyroid and
      craniofacial defects. Although a pioneer activity of FOXE1 in thyroid development
      has been reported, FOXE1 regulation in other contexts remains unexplored. We
      pointed to: (i) a role of FOXE1 in controlling the expression of MSX1 and TGF
      beta3 relevant in craniofacial development and (ii) a causative part of FOXE1
      mutations or mice Foxe1(-/-) genotype in the pathogenesis of cleft palate in the
      Bamforth-Lazarus syndrome. The MSX1 and TGF-beta3 up-regulation in response to
      FOXE1 at both transcriptional and translational levels and the recruitment of
      FOXE1 to specific binding motifs, together with the transactivation of the
      promoters of these genes, indicate that MSX1 and TGF-beta3 are direct FOXE1
      targets. Moreover, we showed that all the known forkhead-domain mutations, but
      not the polyalanine-stretch polymorphisms, affect the FOXE1 ability to bind to
      and transactivate MSX1 and TGF-beta3 promoters. In 14-day Foxe1(-/-) mice
      embryos, Tgf-beta3 and Msx1 mRNAs were almost absent in palatal shelves compared
      with Foxe1(+/-) embryos. Our findings give new insights into the genetic
      mechanisms underlying the Bamforth-Lazarus syndrome-associated facial defects.

PMID- 21177255
TI  - In vivo cell-autonomous transcriptional abnormalities revealed in mice expressing
      mutant huntingtin in striatal but not cortical neurons.
AB  - Huntington's disease (HD), caused by a CAG repeat expansion in the huntingtin
      (HTT) gene, is characterized by abnormal protein aggregates and motor and
      cognitive dysfunction. Htt protein is ubiquitously expressed, but the striatal
      medium spiny neuron (MSN) is most susceptible to dysfunction and death. Abnormal
      gene expression represents a core pathogenic feature of HD, but the relative
      roles of cell-autonomous and non-cell-autonomous effects on transcription remain
      unclear. To determine the extent of cell-autonomous dysregulation in the striatum
      in vivo, we examined genome-wide RNA expression in symptomatic D9-N171-98Q
      (a.k.a. DE5) transgenic mice in which the forebrain expression of the first 171
      amino acids of human Htt with a 98Q repeat expansion is limited to MSNs.
      Microarray data generated from these mice were compared with those generated on
      the identical array platform from a pan-neuronal HD mouse model, R6/2, carrying
      two different CAG repeat lengths, and a relatively high degree of overlap of
      changes in gene expression was revealed. We further focused on known canonical
      pathways associated with excitotoxicity, oxidative stress, mitochondrial
      dysfunction, dopamine signaling and trophic support. While genes related to
      excitotoxicity, dopamine signaling and trophic support were altered in both DE5
      and R6/2 mice, which may be either cell autonomous or non-cell autonomous, genes
      related to mitochondrial dysfunction, oxidative stress and the peroxisome
      proliferator-activated receptor are primarily affected in DE5 transgenic mice,
      indicating cell-autonomous mechanisms. Overall, HD-induced dysregulation of the
      striatal transcriptome can be largely attributed to intrinsic effects of mutant
      Htt, in the absence of expression in cortical neurons.

PMID- 21177257
TI  - Parkin degrades estrogen-related receptors to limit the expression of monoamine
      oxidases.
AB  - Parkin, whose mutations cause Parkinson disease (PD), controls oxidative stress
      by limiting the expression of monoamine oxidases (MAO)--mitochondrial enzymes
      responsible for the oxidative de-amination of dopamine. Here, we show that parkin
      performed this function by increasing the ubiquitination and degradation of
      estrogen-related receptors (ERR), orphan nuclear receptors that play critical
      roles in the transcription regulation of many nuclear-encoded mitochondrial
      proteins. All three ERRs (alpha, beta and gamma) increased the transcription of
      MAOs A and B; the effects were abolished by parkin, but not by its PD-linked
      mutants. Parkin bound to ERRs and increased their ubiquitination and degradation.
      In fibroblasts from PD patients with parkin mutations or brain slices from parkin
      knockout mice, degradation of ERRs was significantly attenuated. The results
      reveal the molecular mechanism by which parkin suppresses the transcription of
      MAOs to control oxidative stress induced by dopamine oxidation.

PMID- 21177259
TI  - Effects of elevated CO2 concentration on seed production in C3 annual plants.
AB  - The response of seed production to CO(2) concentration ([CO(2)]) is known to vary
      considerably among C(3) annual species. Here we analyse the interspecific
      variation in CO(2) responses of seed production per plant with particular
      attention to nitrogen use. Provided that seed production is limited by nitrogen
      availability, an increase in seed mass per plant results from increase in seed
      nitrogen per plant and/or from decrease in seed nitrogen concentration ([N]).
      Meta-analysis reveals that the increase in seed mass per plant under elevated
      [CO(2)] is mainly due to increase in seed nitrogen per plant rather than seed [N]
      dilution. Nitrogen-fixing legumes enhanced nitrogen acquisition more than non
      nitrogen-fixers, resulting in a large increase in seed mass per plant. In
      Poaceae, an increase in seed mass per plant was also caused by a decrease in seed
      [N]. Greater carbon allocation to albumen (endosperm and/or perisperm) than the
      embryo may account for [N] reduction in grass seeds. These differences in CO(2)
      response of seed production among functional groups may affect their fitness,
      leading to changes in species composition in the future high-[CO(2)] ecosystem.

PMID- 21177258
TI  - KASH protein Syne-2/Nesprin-2 and SUN proteins SUN1/2 mediate nuclear migration
      during mammalian retinal development.
AB  - Nuclear movement relative to cell bodies is a fundamental process during certain
      aspects of mammalian retinal development. During the generation of photoreceptor
      cells in the cell division cycle, the nuclei of progenitors oscillate between the
      apical and basal surfaces of the neuroblastic layer (NBL). This process is termed
      interkinetic nuclear migration (INM). Furthermore, newly formed photoreceptor
      cells migrate and form the outer nuclear layer (ONL). In the current study, we
      demonstrated that a KASH domain-containing protein, Syne-2/Nesprin-2, as well as
      SUN domain-containing proteins, SUN1 and SUN2, play critical roles during INM and
      photoreceptor cell migration in the mouse retina. A deletion mutation of Syne
      2/Nesprin-2 or double mutations of Sun1 and Sun2 caused severe reduction of the
      thickness of the ONL, mislocalization of photoreceptor nuclei and profound
      electrophysiological dysfunction of the retina characterized by a reduction of a-
      and b-wave amplitudes. We also provide evidence that Syne-2/Nesprin-2 forms
      complexes with either SUN1 or SUN2 at the nuclear envelope to connect the nucleus
      with dynein/dynactin and kinesin molecular motors during the nuclear migrations
      in the retina. These key retinal developmental signaling results will advance our
      understanding of the mechanism of nuclear migration in the mammalian retina.

PMID- 21177260
TI  - Analysis of lognormally distributed exposure data with repeated measures and
      values below the limit of detection using SAS.
AB  - Studies of determinants of occupational exposure frequently involve left-censored
      lognormally distributed data, often with repeated measures. Left censoring occurs
      when observations are below the analytical limit of detection (LOD); repeated
      measures data results from taking multiple measurements on the same worker. A
      common method of dealing with this type of data has been to substitute a value
      (such as LOD/2) for the censored data followed by statistical analysis using the
      'usual' methods. Recently, maximum likelihood estimation (MLE) methods have been
      employed to reduce bias associated with the substitution method. We compared
      substitution and MLE methods using simulated lognormally distributed exposure
      data subjected to varying amounts of censoring using two procedures available in
      SAS: LIFEREG and NLMIXED. In these simulations, the MLE method resulted in less
      bias and performed well even for censoring up to 80%, whereas the substitution
      method resulted in considerable bias. We illustrate the NLMIXED procedure using a
      dataset of chlorpyrifos air measurements collected from termiticide applicators
      on consecutive days over a 5-day workweek. We provide sample SAS code for several
      situations including one and two groups, with and without repeated measures,
      random slopes, and nested random effects.

PMID- 21177261
TI  - Development of a permeation panel to test dermal protective clothing against
      sprayed coatings.
AB  - OBJECTIVES: Design, construct, and characterize an apparatus to evaluate dermal
      protective clothing for resistance to polymerizing materials. Specifically, we
      evaluated the permeation of the most common glove material used in automotive
      collision repair (0.10-0.13 mm or 4-5 mil latex) with representative isocyanate
      containing clear coats. Our ultimate goal is to make informed recommendations on
      dermal protective materials to prevent isocyanate exposures and reduce the
      likelihood of occupational illness in automotive collision repair and other
      industries. METHODS: A novel permeation panel was developed to assess dermal
      protective clothing. With this apparatus, up to eight test materials may be
      evaluated under typical-spray application conditions. Solid collection media
      comprised of 1-(2-pyridyl)-piperazine (2-PP)-coated fiberglass filters or
      colorimetric SWYPETM pads were placed behind test materials to capture permeants.
      The 2-PP-coated filters were subsequently analyzed using a modified OSHA42/PV2034
      method. Color change in the SWYPEs provided an immediate field estimate of
      breakthrough time. In addition, Teflon filters were mounted proximal to the
      permeation cells to measure the mass of clear coat applied to the panel and to
      evaluate loading homogeneity. This study evaluated the permeation of isocyanates
      through 0.10-0.13 mm latex glove material at a fixed time (30 min post-spraying)
      and over a time course (6-91 min post-spraying). RESULTS: Monomers 1,6
      hexamethylene diisocyanate (HDI) and isophorone diisocyanate (IPDI) permeated
      through (0.10-0.13 mm) latex glove material under typical glove use conditions
      (30 min). The latex glove material exhibited immediate breakthrough, with a
      permeation rate of 2.9 ng min(-1) cm(-2). The oligomeric forms of HDI and IPDI
      did not permeate the latex glove material. The spray application at 71 +/- 5 
      degrees F was fairly homogeneous (33.7 +/- 8 mg weight of dry clear coat per 5
      cm(2)). CONCLUSIONS: The permeation panel is a viable method to assess dermal
      protective clothing performance against polymerizing materials. Thin (0.10-0.13
      mm) latex gloves were determined to be ineffective barriers to the isocyanates
      commonly found in clear coats. Because this type of glove is used frequently in
      auto body shops, the potential for isocyanate exposure is of concern. Permeation
      tests with other dermal protective clothing materials and other clear coat
      formulations are needed to make recommendations about alternative materials.

PMID- 21177262
TI  - Exposure to dust and endotoxin in textile processing workers.
AB  - BACKGROUND: Inhalation of cotton-based particulate has been associated with
      respiratory symptoms and overt lung disease related to endotoxin exposure in some
      studies. This cross-sectional study measures personal exposure to inhalable dust
      and endotoxin in the textile industry of Nepal. METHODS: This study was conducted
      in four sectors (garment making, carpet making, weaving, and recycling) of the
      textile industry in Kathmandu, Nepal. Personal exposure to inhalable dust and
      airborne endotoxin was measured during a full-shift for 114 workers.   RESULTS:
      Personal exposure to cotton dust was generally low [geometric mean (GM) 0.81 mg
      m(-3)) compared to the UK workplace exposure limit (WEL) (2.5 mg m(-3)) but with
      nearly 18% (n = 20) of the workers sampled exceeding the limit. Exposures were
      lowest in the weaving and the garment sector (GM = 0.30 mg m(-3)), higher in the
      carpet sector (GM = 1.16 mg m(-3)), and highest in the recycling sector (GM =
      3.36 mg m(-3)). Endotoxin exposures were high with the overall data (GM = 2160 EU
      m(-3)) being more than 20-fold higher than the Dutch health-based guidance value
      of 90 EU m(-3). The highest exposures were in the recycling sector (GM = 5110 EU
      m(-3)) and the weaving sector (GM = 2440 EU m(-3)) with lower levels in the
      garment sector (GM = 157 EU m(-3)). The highest endotoxin concentrations
      expressed as endotoxin units per milligram inhalable dust were found in the
      weaving sector (GM = 165 EU mg(-1)). There was a statistically significant
      correlation between inhalable dust concentrations and endotoxin concentrations (r
      = 0.37; P < 0.001) and this was particularly strong in the garment (r = 0.82; P =
      0.004) and the carpet sector (r = 0.81; P < 0.001).   CONCLUSIONS: Inhalable dust
      exposures measured in the weaving, carpet, and garment sectors were all below the
      UK WEL for cotton dust. A significant proportion of the measurements from the
      cotton recycling sector were above the UK WEL suggesting that better hygiene
      control measures are required. Airborne endotoxin concentrations in all sectors
      were found to exceed the Dutch health-based guidance limit of 90 EU m(-3) and may
      be associated with respiratory health effects.

PMID- 21177263
TI  - Airborne microorganisms, endotoxin, and (1->3)-beta-D-glucan exposure in
      greenhouses and assessment of respiratory symptoms among workers.
AB  - OBJECTIVES: Greenhouse operations are an important sector of the horticulture
      industry, also known as the Green Industry. The objectives of this study were (i)
      to investigate exposure levels to airborne culturable fungi, bacteria (total
      culturable bacteria and actinomycetes), endotoxin, and (1->3)-beta-D-glucan in
      three Midwest greenhouses during summer and winter using multiple exposure
      assessment methods; (ii) characterize the load of microorganisms on greenhouse
      floors and determine potential microbial source strengths of the floors for
      aerosolizing microbial biocontaminants, and (iii) to estimate the prevalence of
      rhinitis, wheezing, asthma, and other respiratory symptoms/conditions among
      greenhouse workers. METHODS: Stationary inhalable aerosol samples were collected
      from each greenhouse using Button Inhalable Aerosol Samplers. Control samples
      were collected from offices and nearby outdoor locations. A microbial source
      strength tester was used to examine the aerosolization potential of microbial
      contaminants from greenhouse floors. Additionally, surface samples were collected
      by sterile cotton swabs. Temperature, relative humidity, and wind velocity were
      recorded. Airborne culturable fungi, bacteria, and actinomycetes were analyzed in
      the extracts from field samples by cultivation in nutrient agar media. Endotoxin
      and (1->3)-beta-D-glucan in the extracts from field samples were analyzed by
      specific kinetic chromogenic Limulus amebocyte lysate assays. The prevalence of
      respiratory symptoms among greenhouse workers (n = 35) and control subjects
      (office workers; n = 14) was estimated with a standardized questionnaire. RESULTS
      AND CONCLUSIONS: The collected data indicate that workers employed in Midwest
      greenhouses may be exposed to elevated levels of inhalable culturable
      microorganisms (fungi and bacteria collectively on the order of 10(2)-10(5) CFU
      m(-3)), endotoxin (10(1)-10(3) EU m(-3)), and (1->3)-beta-D-glucan (10(1)-10(2)
      ng m(-3)). Seasonal variations were observed for some bioaerosol components. The
      prevalence of self-reported respiratory symptoms was generally higher among
      greenhouse workers compared to controls; however, the differences were not
      statistically significant, likely due to the relatively low statistical power of
      the study.

PMID- 21177265
TI  - Effect of fit testing on the protection offered by n95 filtering facepiece
      respirators against fine particles in a laboratory setting.
AB  - OBJECTIVES: This study investigated particle-size-selective protection factors
      (PFs) of four models of N95 filtering facepiece respirators (FFRs) that passed
      and failed fit testing. Particle size ranges were representative of individual
      viruses and bacteria (aerodynamic diameter d(a) = 0.04-1.3 MUm). METHODS:
      Standard respirator fit testing was followed by particle-size-selective
      measurement of PFs while subjects wore N95 FFRs in a test chamber. PF values
      obtained for all subjects were then compared to those obtained for the subjects
      who passed the fit testing. RESULTS: Overall fit test passing rate for all four
      models of FFRs was 67%. Of these, 29% had PFs <10 (the Occupational Safety and
      Health Administration Assigned Protection Factor designated for this type of
      respirator). When only subjects that passed fit testing were included, PFs
      improved with 9% having values <10. On average, the PFs were 1.4 times
      (29.5/21.5) higher when only data for those who passed fit testing were included.
      The minimum PFs were consistently observed in the particle size range of 0.08-0.2
      MUm. CONCLUSIONS: Overall PFs increased when subjects passed fit testing. The
      results support the value of fit testing but also show for the first time that
      PFs are dependent on particle size regardless of fit testing status.

PMID- 21177266
TI  - Disorders of iron metabolism. Part 1: molecular basis of iron homoeostasis.
AB  - IRON FUNCTIONS: Iron is an essential micronutrient, as it is required for
      satisfactory erythropoietic function, oxidative metabolism and cellular immune
      response. IRON PHYSIOLOGY: Absorption of dietary iron (1-2 mg/day) is tightly
      regulated and just balanced against iron loss because there are no active iron
      excretory mechanisms. Dietary iron is found in haem (10%) and non-haem (ionic,
      90%) forms, and their absorption occurs at the apical surface of duodenal
      enterocytes via different mechanisms. Iron is exported by ferroportin 1 (the only
      putative iron exporter) across the basolateral membrane of the enterocyte into
      the circulation (absorbed iron), where it binds to transferrin and is transported
      to sites of use and storage. Transferrin-bound iron enters target cells-mainly
      erythroid cells, but also immune and hepatic cells-via receptor-mediated
      endocytosis. Senescent erythrocytes are phagocytosed by reticuloendothelial
      system macrophages, haem is metabolised by haem oxygenase, and the released iron
      is stored as ferritin. Iron will be later exported from macrophages to
      transferrin. This internal turnover of iron is essential to meet the requirements
      of erythropoiesis (20-30 mg/day). As transferrin becomes saturated in iron
      overload states, excess iron is transported to the liver, the other main storage
      organ for iron, carrying the risk of free radical formation and tissue damage.
      REGULATION OF IRON HOMOEOSTASIS: Hepcidin, synthesised by hepatocytes in response
      to iron concentrations, inflammation, hypoxia and erythropoiesis, is the main
      iron-regulatory hormone. It binds ferroportin on enterocytes, macrophages and
      hepatocytes triggering its internalisation and lysosomal degradation.
      Inappropriate hepcidin secretion may lead to either iron deficiency or iron
      overload.

PMID- 21177264
TI  - Workplace bullying and psychotropic drug use: the mediating role of physical and
      mental health status.
AB  - OBJECTIVES: The association between workplace bullying and psychotropic drug use
      is not well established. This study was aimed at exploring the association
      between workplace bullying, and its characteristics, and psychotropic drug use
      and studying the mediating role of physical and mental health. METHODS: The study
      population consisted of a random sample of 3132 men and 4562 women of the working
      population in the south-east of France. Workplace bullying, evaluated using the
      validated instrument elaborated by Leymann, and psychotropic drug use, as well as
      covariates, were measured using a self-administered questionnaire. Covariates
      included age, marital status, presence of children, education, occupation,
      working hours, night work, physico-chemical exposures at work, self-reported
      health, and depressive symptoms. Statistical analysis was performed using
      logistic regression analysis and was carried out separately for men and women.
      RESULTS: Workplace bullying was strongly associated with psychotropic drug use.
      Past exposure to bullying increased the risk for this use. The more frequent and
      the longer the exposure to bullying, the stronger the association with
      psychotropic drug use. Observing bullying on someone else at the workplace was
      associated with psychotropic drug use. Adjustment for covariates did not modify
      the results. Additional adjustment for self-reported health and depressive
      symptoms reduced the magnitude of the associations, especially for men.
      CONCLUSIONS: The association between bullying and psychotropic drug use was found
      to be significant and strong and was partially mediated by physical and mental
      health.

PMID- 21177267
TI  - Practical management of antibiotic allergy in adults.
AB  - This review looks at the main issues around immediate hypersensitivity and the
      role and limitations of testing. The majority of literature on antibiotic
      hypersensitivity relates to beta-lactam antibiotics, mainly because of the heavy
      usage of this class of drugs. Concerns around cross-reactivity always worry
      clinicians, particularly in the emergency situation. Reasonable data now exist in
      relation to beta-lactam antibiotics and derivatives, which enable appropriate
      risk management to be undertaken. The available literature for other classes of
      antibiotics is also discussed.

PMID- 21177268
TI  - Disorders of iron metabolism. Part II: iron deficiency and iron overload.
AB  - MAIN DISORDERS OF IRON METABOLISM: Increased iron requirements, limited external
      supply, and increased blood loss may lead to iron deficiency (ID) and iron
      deficiency anaemia. In chronic inflammation, the excess of hepcidin decreases
      iron absorption and prevents iron recycling, resulting in hypoferraemia and iron
      restricted erythropoiesis, despite normal iron stores (functional iron
      deficiency), and finally anaemia of chronic disease (ACD), which can evolve to
      ACD plus true ID (ACD+ID). In contrast, low hepcidin expression may lead to
      hereditary haemochromatosis (HH type I, mutations of the HFE gene) and type II
      (mutations of the hemojuvelin and hepcidin genes). Mutations of transferrin
      receptor 2 lead to HH type III, whereas those of the ferroportin gene lead to HH
      type IV. All these syndromes are characterised by iron overload. As transferrin
      becomes saturated in iron overload states, non-transferrin bound iron appears.
      Part of this iron is highly reactive (labile plasma iron), inducing free radical
      formation. Free radicals are responsible for the parenchymal cell injury
      associated with iron overload syndromes. ROLE OF LABORATORY TESTING IN DIAGNOSIS:
      In iron deficiency status, laboratory tests may provide evidence of iron
      depletion in the body or reflect iron deficient red cell production. Increased
      transferrin saturation and/or ferritin levels are the main cues for further
      investigation of iron overload. The appropriate combination of different
      laboratory tests with an integrated algorithm will help to establish a correct
      diagnosis of iron overload, iron deficiency and anaemia. REVIEW OF TREATMENT
      OPTIONS: Indications, advantages and side effects of the different options for
      treating iron overload (phlebotomy and iron chelators) and iron deficiency (oral
      or intravenous iron formulations) will be discussed.

PMID- 21177269
TI  - National and international interlaboratories comparisons: a tool for the
      validation of in vitro and in vivo methods.
AB  - The metrological evaluation is indispensable to objectively prove the capability
      of the medical laboratory to perform analysis. The comparison of analytical
      performances regarding the accuracy and the reproducibility of the available
      methods is a real interest of international comparison exercises, especially as
      the participation to comparison exercises is becoming a requirement for
      accredited laboratories. Interlaboratory tests are a means of assessing the
      analytical coherence of medical laboratories. In radiotoxicology, this kind of
      exercise makes it possible to keep up with laboratory know-how and with the
      evolution and relative performances of analytical techniques. The objective of
      this paper will be to present and discuss the main principle of proficiency
      testing in radiobioassay field illustrated by exercises organised in France for
      in vivo monitoring and for in vitro analysis.

PMID- 21177270
TI  - Liulin-type spectrometry-dosimetry instruments.
AB  - The main purpose of Liulin-type spectrometry-dosimetry instruments (LSDIs) is
      cosmic radiation monitoring at the workplaces. An LSDI functionally is a low
      mass, low power consumption or battery-operated dosemeter. LSDIs were calibrated
      in a wide range of radiation fields, including radiation sources, proton and
      heavy-ion accelerators and CERN-EC high-energy reference field. Since 2000, LSDIs
      have been used in the scientific programmes of four manned space flights on the
      American Laboratory and ESA Columbus modules and on the Russian segment of the
      International Space Station, one Moon spacecraft and three spacecraft around the
      Earth, one rocket, two balloons and many aircraft flights. In addition to
      relative low price, LSDIs have proved their ability to qualify the radiation
      field on the ground and on the above-mentioned carriers.

PMID- 21177271
TI  - Microdosimetric characteristics of proton beams from 50 keV to 200 MeV.
AB  - Proton beams are of growing interest for radiation therapy due to their special
      physical and radiobiological properties. Microdosimetric characteristics of
      proton beams have strong influence on the relative biological effectiveness for
      each biological system. This study focused on the microdosimetric characteristics
      of monoenergetic protons from 50 keV to 200 MeV. Monte Carlo techniques were used
      to simulate track segments of protons in water. Dose mean lineal energies were
      derived to characterise proton beams with changing kinetic energy and changing
      radiation qualities at various depths and within spread-out Bragg peaks of clinic
      interests.

PMID- 21177273
TI  - Reasoned argument for the cessation of radiofrequency delivery should atrial
      fibrillation start during slow pathway ablation.

PMID- 21177272
TI  - The effects of high ambient radon on thermoluminescence dosimetry readings.
AB  - The effect of a high level of ambient (222)Rn gas on thermoluminescence
      dosemeters (TLDs) is examined. Groups of LiF:Mg,Ti and CaF(2):Dy TLDs were
      exposed to (222)Rn under controlled environmental conditions over ~7 d using a
      luminous (226)Ra aircraft dial. LiF:Mg,Ti TLDs were tested bare, and both types
      were tested mounted in cards used for environmental dosimetry and mounted in
      cards enclosed in plastic badges. A passive continuous radon monitor was used to
      measure the (222)Rn level in the small chamber during the experiments. The data
      were analysed to determine the relationship between the integrated (222)Rn level
      and the TLD response. Although both LiF:Mg,Ti and CaF(2):Dy TLDs showed a strong
      response to (222)Rn, the badges prevented measurable radon detection by the TLDs
      within. The TLDs were not used to directly measure the radon concentration;
      rather, a correction for its influence was desired.

PMID- 21177274
TI  - Three left ventricular leads required for improved haemodynamic and clinical
      status of a patient with very severe heart failure and a narrow QRS duration.
AB  - A 65-year-old man with severe idiopathic cardiomyopathy was referred to our
      centre with New York Heart Association (NYHA) IV heart failure requiring
      continuous dobutamine infusion. Implantation of three left ventricle (LV) leads
      was associated with a significant haemodynamic improvement. After 6 months of tri
      LV pacing the patient has improved NYHA class from IV to II and the LV ejection
      fraction from 15 to 21%.

PMID- 21177275
TI  - Two completely separated arrhythmias in one single heart chamber.
AB  - A 61-year-old male patient underwent an electrophysiological study and ablation
      for symptomatic atypical atrial flutter which was most likely related to previous
      intraoperative cryoablation for treatment of paroxysmal atrial fibrillation
      during open heart surgery. During the procedure, a tachycardia was induced in the
      electrically isolated left inferior pulmonary vein (PV). With the routine
      induction protocol, perimitral flutter was induced, whereas, independently, the
      PV tachycardia was still maintained. After ablation of the mitral isthmus, no
      tachycardias were inducible anymore.

PMID- 21177276
TI  - Weapons development programme before the lead war.

PMID- 21177278
TI  - Stem cell infusion into the vein of Marshall.
AB  - The vein of Marshall (VOM) and related cardiac ganglia have been clearly
      implicated in atrial fibrillation. Electrophysiological procedures have targeted
      these sites of autonomic innervation. However, targeting the exact sites has
      proven technically challenging. Identifying the VOM and infusing stem cells may
      ablate related ganglia autonomic function and offer an innovative treatment for
      atrial fibrillation.

PMID- 21177277
TI  - A real-time tip manometer for radiofrequency catheter ablation: new toy or useful
      tool?

PMID- 21177279
TI  - Endocardial pacemaker implantation: what is the lead course?

PMID- 21177280
TI  - Validation of the Institut Curie simplified prognostic score for breast cancer
      meningeal carcinomatosis.

PMID- 21177281
TI  - Association of adverse drug reactions with drug-drug and drug-disease
      interactions in frail older outpatients.

PMID- 21177282
TI  - Combining phage and staphylococcal surface display for generation of ErbB3
      specific Affibody molecules.
AB  - Emerging evidence suggests that the catalytically inactive ErbB3 (HER3) protein
      plays a fundamental role in normal tyrosine kinase receptor signaling as well as
      in aberrant functioning of these signaling pathways, resulting in several forms
      of human cancers. ErbB3 has recently also been implicated in resistance to ErbB2
      targeting therapies. Here we report the generation of high-affinity ErbB3
      specific Affibody molecules intended for future molecular imaging and
      biotherapeutic applications. Using a high-complexity phage-displayed Affibody
      library, a number of ErbB3 binders were isolated and specific cell-binding
      activity was demonstrated in immunofluorescence microscopic studies.
      Subsequently, a second-generation library was constructed based on sequences of
      the candidates from the phage display selection. By exploiting the sensitive
      affinity discrimination capacity of a novel bacterial surface display technology,
      the affinity of candidate Affibody molecules was further increased down to
      subnanomolar affinity. In summary, the demonstrated specific targeting of native
      ErbB3 receptor on human cancer cell lines as well as competition with the
      heregulin/ErbB3 interaction indicates that these novel biological agents may
      become useful tools for diagnostic and therapeutic targeting of ErbB3-expressing
      cancers. Our studies also highlight the powerful approach of combining the
      advantages of different display technologies for generation of functional high
      affinity protein-based binders. Potential future applications, such as
      radionuclide-based diagnosis and treatment of human cancers are discussed.

PMID- 21177283
TI  - Interleukin-15:Interleukin-15 receptor alpha scaffold for creation of multivalent
      targeted immune molecules.
AB  - Human interleukin-15 (hIL-15) and its receptor alpha (hIL-15Ralpha) are co
      expressed in antigen presenting cells allowing trans-presentation of the cytokine
      to immune effector cells. We exploited the high-affinity interactions between hIL
      15 and the extracellular hIL-15Ralpha sushi domain (hIL-15RalphaSu) to create a
      functional scaffold for the design of multispecific fusion protein complexes.
      Using single-chain T cell receptors (scTCRs) as recognition domains linked to the
      IL-15:IL-15Ralpha scaffold, we generated both bivalent and bispecific complexes.
      In these fusions, the scTCR domains retain the antigen-binding activity and the
      hIL-15 domain exhibits receptor binding and biological activity. As expected,
      bivalent scTCR fusions exhibited improved antigen binding due to increased
      avidity, whereas fusions comprising two different scTCR domains were capable of
      binding two cognate peptide/MHC complexes. Bispecific molecules containing scTCR
      and scCD8alphabeta domains also exhibit enhanced binding to peptide/MHC
      complexes, demonstrating that the IL-15:IL-15Ralpha scaffold displays flexibility
      necessary to support multi-domain interactions with a given target. Surprisingly,
      functional heterodimeric molecules could be formed by co-expressing the TCR alpha
      and beta chains separately as fusions to the hIL-15 and hIL-15RalphaSu domains.
      Together, these properties indicate that the hIL-15 and hIL-15RalphaSu domains
      can be used as versatile, functional scaffold for generating novel targeted
      immune molecules.

PMID- 21177284
TI  - Comparison between ultrasound-guided transversus abdominis plane and conventional
      ilioinguinal/iliohypogastric nerve blocks for day-case open inguinal hernia
      repair.
AB  - BACKGROUND: Transversus abdominis plane (TAP) block has been reported to provide
      effective analgesia after lower abdominal surgery, but there are few data
      comparing ilioinguinal/iliohypogastric nerve (IHN) block with ultrasound-guided
      TAP block in patients undergoing inguinal hernia repair. METHODS: Two hundred and
      seventy-three patients undergoing day-case open inguinal hernia repair with a
      mesh were randomly allocated to receive either ultrasound-guided TAP block or
      blind IHN block with levobupivacaine 0.5%, before surgery. Patients were
      monitored for visual analogue scale (VAS) scores at rest (in the post-anaesthesia
      care unit, and at 4 and 12 h) and at rest and during movement (at 24, 48 h, 3 and
      6 months). Pain at 6 months was also assessed using the DN4 questionnaire for
      neuropathic pain. RESULTS: Median VAS pain scores at rest were lower in the
      ultrasound-guided TAP group at 4 h (11 vs 15, P=0.04), at 12 h (20 vs 30,
      P=0.0014), and at 24 h (29 vs 33, P=0.013). Pain after the first 24 h, at 3 and 6
      months after surgery, and DN4 scores were similar in both groups (P=NS). The
      proportion of patients with VAS >40 mm on movement at 6 months was comparable
      {18.2% [95% CI (12.2-26.1%)] vs 22.4% (15.8-30.6%) in the TAP and IHN groups,
      respectively, P=0.8}. Postoperative morphine requirements were lower during the
      first 24 h in the TAP block group (P=0.03). CONCLUSIONS: Ultrasound-guided TAP
      block provided better pain control than 'blind' IHN block after inguinal hernia
      repair but did not prevent the occurrence of chronic pain.

PMID- 21177285
TI  - Different profiles of main and accessory olfactory bulb mitral/tufted cell
      projections revealed in mice using an anterograde tracer and a whole-mount,
      flattened cortex preparation.
AB  - A whole-mount, flattened cortex preparation was developed to compare profiles of
      axonal projections from main olfactory bulb (MOB) and accessory olfactory bulb
      (AOB) mitral and tufted (M/T) cells. After injections of the anterograde tracer,
      Phaseolus vulgaris leucoagglutinin, mapping of labeled axons using a Neurolucida
      system showed that M/T cells in the AOB sent axons primarily to the medial and
      posterior lateral cortical amygdala, with minimal branching into the piriform
      cortex. By contrast, M/T cells in the MOB displayed a network of collaterals that
      branched off the primary axon at several levels of the lateral olfactory tract
      (LOT). Collaterals emerging from the LOT into the anterior piriform cortex were
      often observed crossing into the posterior piriform cortex. M/T cells in the
      dorsal MOB extended fewer collaterals from the primary axon in the rostral LOT
      than did M/T cells from the anterior or ventral MOB. MOB M/T cells that projected
      to the medial amygdala did not do so exclusively, also sending collaterals to the
      anterior cortical amygdala as well as to olfactory cortical regions. This
      arrangement may be related to the ability of social experience to modify the
      response of mice to volatile pheromones detected by the main olfactory system.

PMID- 21177286
TI  - beta2-adrenergic receptors inhibit the expression of collagen type II in growth
      plate chondrocytes by stimulating the AP-1 factor Jun-B.
AB  - The sympathetic nervous system can regulate both osteoblast and chondrocyte
      growth and activity through beta(2)-adrenergic receptors (beta(2)-AR). We have
      shown previously that beta(2)-AR activate both adenylyl cyclase and mitogen
      activated protein kinases ERK1/2 in growth plate chondrocytes prepared from ribs
      of embryonic E18.5 mice. Here we examined beta(2)-AR inhibition of collagen type
      II (Col II) expression in growth plate chondrocytes and the molecular pathways
      involved. Stimulation of beta(2)-AR by isoproterenol inhibited Col II mRNA and
      protein levels by ~50% beginning at 2 h, with both remaining suppressed over 24
      h. This inhibition was blocked by propranolol and inhibitors of either MEK1 or
      PKA. Isoproterenol stimulated an AP-1-luciferase reporter and increased the
      expression of AP-1 factors c-Fos, Fra-1, Fra-2, c-Jun, and Jun-B but had no
      effect on Jun-D. Stimulation of AP-1 activity was blocked by inhibitors of MEK1
      or PKA. siRNA inhibition of AP-1 factors showed that depletion of only Jun-B
      attenuated isoproterenol-mediated inhibition of Col II. Transfection with jun-B
      or c-fos showed selective inhibition of Col II mRNA and a Col II luciferase
      reporter construct by jun-B. Isoproterenol as well as jun-B overexpression in the
      chondrocytes also inhibited the expression of Sox-6 mRNA and protein, and
      depletion of Jun-B abrogated beta(2)-AR inhibition of Sox-6. Collectively, these
      findings demonstrate regulation of chondrocyte differentiation through beta(2)-AR
      mediated by ERK1/2 and PKA stimulation of the AP-1 factor Jun-B that inhibits the
      expression of Sox-6 and Col II.

PMID- 21177287
TI  - Loss of intestinal GATA4 prevents diet-induced obesity and promotes insulin
      sensitivity in mice.
AB  - Transcriptional regulation of small intestinal gene expression controls plasma
      total cholesterol (TC) and triglyceride (TG) levels, which are major determinants
      of metabolic diseases. GATA4, a zinc finger domain transcription factor, is
      critical for jejunal identity, and intestinal GATA4 deficiency leads to a
      jejunoileal transition. Although intestinal GATA4 ablation is known to
      misregulate jejunal gene expression, its pathophysiological impact on various
      components of metabolic syndrome remains unknown. Here, we used intestine
      specific GATA4 knockout (GATA4iKO) mice to dissect the contribution of GATA4 on
      obesity development. We challenged adult GATA4iKO mice and control littermates
      with a Western-type diet (WTD) for 20 wk. Our findings show that WTD-fed GATA4iKO
      mice are resistant to diet-induced obesity. Accordingly, plasma TG and TC levels
      are markedly decreased. Intestinal lipid absorption in GATA4iKO mice was strongly
      reduced, whereas luminal lipolysis was unaffected. GATA4iKO mice displayed a
      greater glucagon-like peptide-1 (GLP-1) release on normal chow and even after
      long-term challenge with WTD remained glucose sensitive. In summary, our findings
      show that the absence of intestinal GATA4 has a beneficial effect on decreasing
      intestinal lipid absorption causing resistance to hyperlipidemia and obesity. In
      addition, we show that increased GLP-1 release in GATA4iKO mice decreases the
      risk for development of insulin resistance.

PMID- 21177288
TI  - Glucagon-like peptide-2-stimulated protein synthesis through the PI 3-kinase
      dependent Akt-mTOR signaling pathway.
AB  - Glucagon-like peptide-2 (GLP-2) is a nutrient-responsive neuropeptide that exerts
      diverse actions in the gastrointestinal tract, including enhancing mucosal cell
      survival and proliferation. GLP-2 stimulates mucosal growth in vivo with an
      increased rate of protein synthesis. However, it was unclear whether GLP-2 can
      directly stimulate protein synthesis. The objective was to test critically
      whether GLP-2 receptor (GLP-2R) activation directly stimulates protein synthesis
      through a PI 3-kinase-dependent Akt-mTOR signaling pathway. HEK 293 cells
      (transfected with human GLP-2R cDNA) were treated with human GLP-2 with/without
      pretreatment of PI 3-kinase inhibitor (LY-294002) or mTOR inhibitor (rapamycin).
      Results show that 1) GLP-2 specifically bound to GLP-2R overexpressed in the HEK
      cells with K(a) = 0.22 nM and B(max) = 321 fmol/MUg protein; 2) GLP-2-stimulated
      protein synthesis was dependent on the amount of GLP-2R cDNA and the dosage of
      GLP-2 and reached the plateau among 0.2-2 nM GLP-2; 3) GLP-2-stimulated protein
      synthesis was abolished by the PI 3-kinase inhibitor and mTOR inhibitor; and 4)
      GLP-2-mediated stimulation of phosphorylation on Akt and mTOR was dependent on
      the amount of GLP-2R cDNA transfected and the dosage of GLP-2. In addition, GLP-2
      mediated action and signaling in regulation of protein synthesis were confirmed
      in mouse hippocampal neurons (expressing native GLP-2R). GLP-2 directly
      stimulated protein synthesis of primary cultured neurons in dosage-dependent, PI
      3-kinase-dependent, and rapamycin-sensitive manners, which linked with activation
      of Akt-mTOR signaling pathway as well. We conclude that GLP-2R activation
      directly stimulates protein synthesis by activating the PI 3-kinase-dependent Akt
      mTOR signaling pathway. GLP-2-stimulated protein synthesis may be physiologically
      relevant to maintaining neuronal long-term potentiation and providing secondary
      mediators (namely neuropeptides or growth factors).

PMID- 21177289
TI  - Spectral modulation attenuates molecular, endocrine, and neurobehavioral
      disruption induced by nocturnal light exposure.
AB  - The human eye serves distinctly dual roles in image forming (IF) and non-image
      forming (NIF) responses when exposed to light. Whereas IF responses mediate
      vision, the NIF responses affect various molecular, neuroendocrine, and
      neurobehavioral variables. NIF responses can have acute and circadian phase
      shifting effects on physiological variables. Both the acute and phase-shifting
      effects induced by photic stimuli demonstrate short-wavelength sensitivity
      peaking ~450-480 nm. In the current study, we examined the molecular,
      neuroendocrine, and neurobehavioral effects of completely filtering (0%
      transmission) all short wavelengths <480 nm and all short wavelengths <460 nm or
      partially filtering (~30% transmission) <480 nm from polychromatic white light
      exposure between 2000 and 0800 in healthy individuals. Filtering short
      wavelengths <480 nm prevented nocturnal light-induced suppression of melatonin
      secretion, increased cortisol secretion, and disrupted peripheral clock gene
      expression. Furthermore, subjective alertness, mood, and errors on an objective
      vigilance task were significantly less impaired at 0800 by filtering wavelengths
      <480 nm compared with unfiltered nocturnal light exposure. These changes were not
      associated with significantly increased sleepiness or fatigue compared with
      unfiltered light exposure. The changes in molecular, endocrine, and
      neurobehavioral processes were not significantly improved by completely filtering
      <460 nm or partially filtering <480 nm compared with unfiltered nocturnal light
      exposure. Repeated light-dark cycle alterations as in rotating nightshifts can
      disrupt circadian rhythms and induce health disorders. The current data suggest
      that spectral modulation may provide an effective method of regulating the
      effects of light on physiological processes.

PMID- 21177290
TI  - Drug-specific risk of non-tuberculosis opportunistic infections in patients
      receiving anti-TNF therapy reported to the 3-year prospective French RATIO
      registry.
AB  - BACKGROUND: Anti-tumour necrosis factor (TNF) therapy may be associated with
      opportunistic infections (OIs). OBJECTIVE: To describe the spectrum of non
      tuberculosis OIs associated with anti-TNF therapy and identify their risk
      factors. METHODS: A 3-year national French registry (RATIO) collected all cases
      of OI in patients receiving anti-TNF treatment for any indication in France. A
      case-control study was performed with three controls treated with anti-TNF agents
      per case, matched for gender and underlying inflammatory disease. RESULTS: 45
      cases were collected of non-TB OIs in 43 patients receiving infliximab (n=29),
      adalimumab (n=10) or etanercept (n=4) for rheumatoid arthritis (n=26),
      spondyloarthritides (n=3), inflammatory colitis (n=8), psoriasis (n=1) or other
      conditions (n=5). One-third (33%) of OIs were bacterial (4 listeriosis, 4
      nocardiosis, 4 atypical mycobacteriosis, 3 non-typhoid salmonellosis), 40% were
      viral (8 severe herpes zoster, 3 varicella, 3 extensive herpes simplex, 4
      disseminated cytomegalovirus infections), 22% were fungal (5 pneumocystosis, 3
      invasive aspergillosis, 2 cryptococcosis) and 4% were parasitic (2
      leishmaniasis). Ten patients (23%) required admission to the intensive care unit,
      and four patients (9%) died. Risk factors for OIs were treatment with infliximab
      (OR=17.6 (95% CI 4.3 - 72.9); p<0.0001)or adalimumab (OR=10.0 (2.3 to 44.4);
      p=0.002) versus etanercept, and oral steroid use >10 mg/day or intravenous
      boluses during the previous year (OR=6.3 (2.0 to 20.0); p=0.002). CONCLUSION:
      Various and severe OIs, especially those with intracellular micro-organisms, may
      develop in patients receiving anti-TNF treatment. Monoclonal anti-TNF antibody
      rather than soluble TNF receptor therapy and steroid use >10 mg/day are
      independently associated with OI.

PMID- 21177291
TI  - Interferon beta is associated with type 1 interferon-inducible gene expression in
      dermatomyositis.
AB  - OBJECTIVES: To determine whether type 1 interferon (IFN) proteins in blood are
      associated with downstream type 1 IFN-inducible gene expression in blood from
      patients with myositis. METHODS: IFNalpha, IFNbeta and IFNomega concentrations
      were measured by ELISA in 129 blood samples (from 93 patients with
      dermatomyositis (DM), inclusion body myositis, polymyositis and other muscle
      diseases and from 36 healthy volunteers). Their concentrations were correlated
      with their ability to stimulate type 1 IFN-inducible gene transcription in a
      functional assay for 123 of these samples and the type 1 IFN-inducible blood gene
      expression from 70 of the same samples. RESULTS: Blood IFNbeta concentration was
      uniquely associated with DM (p=0.0004), detectable in 64% of samples from
      patients with untreated or minimally treated DM and 35% of all DM samples
      compared with 6% of other inflammatory myopathy and 6% of healthy volunteer
      samples. Blood IFNbeta, but not IFNalpha or IFNomega, correlated with high blood
      type 1 IFN-inducible gene expression (p=0.01). Healthy volunteer samples with a
      high ELISA signal for IFNalpha and IFNomega lacked functional bioassay activity
      and such a signal was confirmed as artefactual. CONCLUSION: Elevated blood
      IFNbeta protein concentration is associated with DM. Systemic and local
      production of IFNbeta might contribute to, but may not fully explain, the marked
      overproduction of type 1 IFN-inducible transcripts and proteins seen in DM muscle
      and blood.

PMID- 21177292
TI  - Different stages of rheumatoid arthritis: features of the synovium in the
      preclinical phase.
AB  - BACKGROUND: The aetiology of rheumatoid arthritis (RA), a prototype immune
      mediated inflammatory disorder, is poorly understood. It is currently unknown
      whether the disease process starts in the synovium, the primary target of RA, or
      at other sites in the body. OBJECTIVE: To examine, in a prospective study, the
      presence of synovitis in people with an increased risk of developing RA. METHODS:
      Thirteen people without evidence of arthritis, who were positive for IgM
      rheumatoid factor and/or anticitrullinated protein antibodies, were included in
      the study. To evaluate synovial inflammatory changes, all participants underwent
      dynamic contrast-enhanced MRI and arthroscopic synovial biopsy sampling of a knee
      joint at inclusion. Results were compared with knee MRI data and synovial biopsy
      data of 6 and 10 healthy controls, respectively. RESULTS: MRI findings evaluated
      by measurement of maximal enhancement, rate of enhancement, synovial volume and
      enhancement shape curve distribution were similar between the autoantibody
      positive subjects and the healthy controls. Consistent with these findings, all
      but one autoantibody-positive subject showed very low scores for phenotypic
      markers, adhesion molecules and vascularity, all in the same range as those in
      normal controls. The one person with higher scores had patellofemoral joint space
      narrowing. CONCLUSION: Subclinical inflammation of the synovium does not coincide
      with the appearance of serum autoantibodies during the pre-RA stage. Thus,
      systemic autoimmunity precedes the development of synovitis, suggesting that a
      'second hit' is involved. This study supports the rationale for exploring
      preventive strategies aimed at interfering with the humoral immune response
      before synovial inflammation develops.

PMID- 21177293
TI  - The cannabinoid WIN55, 212-2 abrogates dermal fibrosis in scleroderma bleomycin
      model.
AB  - OBJECTIVES: There is increasing evidence that the endocannabinoid system may be
      involved in pathological fibrosis, and that its modulation might limit fibrotic
      responses. The aim of this study was to examine the capacity of a synthetic
      cannabinoid receptor agonist to modify skin fibrosis in the bleomycin mouse model
      of scleroderma. METHODS: Skin fibrosis was induced by local injections of
      bleomycin in two groups of DBA/2J mice. One group was cotreated with the
      synthetic cannabinoid WIN55,212-2 at 1 mg/kg/day. Skin fibrosis was evaluated by
      histology and skin thickness and hydroxyproline content were quantified. Markers
      of fibroblast activation, including alpha smooth muscle actin and the profibrotic
      cytokines transforming growth factor (TGF)beta, connective tissue growth factor
      (CTGF) and platelet-derived growth factor (PDGF)-BB, were examined. Levels of
      PSMAD2/3, which are crucial in extracellular matrix overproduction, were
      analysed. RESULTS: Bleomycin treatment induced typical skin fibrosis. Upon
      WIN55,212-2 treatment dermal fibrosis was completely prevented. Subcutaneous
      inflammatory cell infiltration, dermal thickness and collagen content resulted
      similar to those of the control group. The synthetic cannabinoid prevented
      fibroblasts activation induced by bleomycin, paralleled by a strong inhibition of
      TGFbeta, CTGF and PDGF-BB expression. Phosphorylation of SMAD2/3 was
      significantly downregulated after WIN55,212-2 exposure. CONCLUSIONS: Taken
      together, the results indicate that the synthetic cannabinoid WIN55,212-2 is
      capable of preventing skin fibrosis in a mouse model of scleroderma.

PMID- 21177294
TI  - Mitochondrial DNA haplogroups and serum levels of proteolytic enzymes in patients
      with osteoarthritis.
AB  - OBJECTIVE: To analyse the influence of mitochondrial DNA haplogroups, as well as
      the radiographic grade, on serum levels of proteolytic enzymes in patients with
      osteoarthritis (OA). METHODS: Serum levels of metalloproteinase-1 (MMP-1), MMP-3,
      MMP-13, myeloperoxidase and cathepsin K were analysed in 73 patients with OA and
      77 healthy controls carrying the haplogroups J, U and H, by ELISA. Knee and hip
      radiographs were classified according to Kellgren and Lawrence (K/L) scoring from
      grade 0 to grade IV. Non-parametric and multiple regression analyses were
      performed to test the effects of clinical variables, including gender, age,
      smoking status, diagnosis, haplogroups and radiological K/L grade on serum levels
      of these enzymes. RESULTS: A significant influence of the haplogroups on the
      serum levels of MMP-3 and MMP-13 was detected (p=0.027 and p=0.035,
      respectively). Patients with OA with haplogroup H showed higher serum levels of
      MMP-3 than healthy controls. Serum levels of MMP-13 were significantly higher in
      patients with OA (p<0.001), and carriers of the haplogroup J showed lower levels
      than H carriers. Besides, levels of MMP-13 were proportionally higher in
      radiological groups B (K/L grade II and III) and C (K/L grade IV) than in group A
      (K/L grade 0 and I) (p=0.005). CONCLUSIONS: This study shows that haplogroups
      have a significant influence on serum levels of MMP-3 and MMP-13. The influence
      of the haplogroups on serum levels of MMP-3 is clearly dependent on the
      diagnosis, whereas the influence of the haplogroups on serum levels of MMP-13 is
      independent of diagnosis.

PMID- 21177296
TI  - Effectiveness of initial treatment allocation based on expert opinion for
      prevention of rapid radiographic progression in daily practice of an early RA
      cohort.
AB  - OBJECTIVES: To evaluate expert treatment selection for early rheumatoid arthritis
      and to validate a prediction model for rapid radiographic progression (RRP) in
      daily practice. METHODS: Patients received initial combination therapy with
      steroids (ICTS) or disease-modifying antirheumatic drug monotherapy (IMT) after
      informal evaluation of prognostic factors, followed by a tight control strategy.
      Changes in Sharp/van der Heijde score (total Sharp score (TSS)) of >5 units over
      1 year (=RRP) were documented. The mean change in TSS and proportion with RRP
      were compared between groups. Based on the 28 swollen joint count, rheumatoid
      factor titre and C reactive protein/erythrocyte sedimentation rate, patients were
      placed in the ASPIRE prediction matrix, yielding a RRP risk. Numbers needed to
      treat (NNT) intensively to avoid one RRP after 1 year were calculated. RESULTS:
      The mean change in TSS after 1 year and the proportion with RRP was lower in the
      ICTS group (n=37) than in the IMT group (n=43). The mean calculated risk of RRP
      was higher in patients with radiographic progression. The mean NNT intensively to
      prevent RRP was lower in the ICTS group than in the IMT group. The positive
      predictive value of NNT for RRP prevention was 12.6%, but the negative predictive
      value reached 100%. CONCLUSION: ICTS seems more effective in preventing RRP than
      IMT. The predictive matrix model could be helpful in preventing overtreatment in
      practice.

PMID- 21177295
TI  - Insights into the genetic architecture of osteoarthritis from stage 1 of the
      arcOGEN study.
AB  - OBJECTIVES: The genetic aetiology of osteoarthritis has not yet been elucidated.
      To enable a well-powered genome-wide association study (GWAS) for osteoarthritis,
      the authors have formed the arcOGEN Consortium, a UK-wide collaborative effort
      aiming to scan genome-wide over 7500 osteoarthritis cases in a two-stage genome
      wide association scan. Here the authors report the findings of the stage 1
      interim analysis. METHODS: The authors have performed a genome-wide association
      scan for knee and hip osteoarthritis in 3177 cases and 4894 population-based
      controls from the UK. Replication of promising signals was carried out in silico
      in five further scans (44,449 individuals), and de novo in 14 534 independent
      samples, all of European descent. RESULTS: None of the association signals the
      authors identified reach genome-wide levels of statistical significance,
      therefore stressing the need for corroboration in sample sets of a larger size.
      Application of analytical approaches to examine the allelic architecture of
      disease to the stage 1 genome-wide association scan data suggests that
      osteoarthritis is a highly polygenic disease with multiple risk variants
      conferring small effects. CONCLUSIONS: Identifying loci conferring susceptibility
      to osteoarthritis will require large-scale sample sizes and well-defined
      phenotypes to minimise heterogeneity.

PMID- 21177297
TI  - Lupus Atherosclerosis Prevention Study (LAPS).
AB  - BACKGROUND: Cardiovascular disease is one of the major causes of death in
      systemic lupus erythematosus (SLE). A study was undertaken to investigate whether
      treatment with statins would reduce subclinical measures of atherosclerosis over
      a 2-year period. METHODS: 200 patients with SLE without clinical cardiovascular
      disease were randomised to receive atorvastatin 40 mg daily or an identical
      placebo. At baseline and after 2 years of follow-up, helical CT scanning (for
      coronary artery calcium) and carotid duplex (for intima media thickness/plaque)
      were performed. Patients were seen for measures of disease activity at 1 month, 3
      months and quarterly thereafter. The primary outcome variable was change in
      coronary artery calcium. RESULTS: At baseline, 43% had coronary artery calcium.
      At 2 years there was no significant difference between the groups in progression
      of coronary artery calcium, carotid intima media thickness or carotid plaque.
      There was no significant difference between the groups in disease activity,
      measures of inflammation or endothelial cell activation. CONCLUSION: This study
      provides no evidence that atorvastatin reduces subclinical measures of
      atherosclerosis or disease activity over 2 years in patients with SLE. In fact,
      it does not appear to reduce biochemical measures of inflammation. The anti
      inflammatory effects of statins observed in the general population were not
      replicated in this SLE clinical trial. Clinicaltrials.gov (NCT 00120887).

PMID- 21177298
TI  - Rapidly growing aortic arch aneurysm in Behcet's disease.
AB  - We present a patient with a nine-year history of Behcet's disease (BD), who
      developed a rapidly expanding aneurysm of the aortic arch. Three-dimensional
      computed tomography demonstrated a saccular aortic arch aneurysm with a maximal
      diameter of 5 cm. No bacteria were detected by serial blood cultures. The
      aneurysm, however, showed a multi-lobular cavity, mimicking an infectious
      aneurysm. Therefore, we prescribed antibacterial agents for one week. The patient
      still had a high-fever and an elevated C-reactive protein level thereafter.
      Aortic arch replacement was performed emergently. Because we were unable to
      determine whether the aneurysm was caused by infection or BD, the implanted
      prosthetic graft and the anastomotic sites were covered with a pedicle graft of
      the greater omentum, and we continued to administer antibacterial agents for four
      weeks postoperatively. The pathological examination showed neither bacteria nor
      cystic medial necrosis in the resected aortic wall. Inflammatory changes with
      eosinophilic infiltration were recognized mainly around the adventitia near the
      aneurysm. The patient had a favorable postoperative course without any
      complications.

PMID- 21177299
TI  - Beating heart versus conventional mitral valve surgery.
AB  - OBJECTIVES: The present study aimed to compare the results of beating heart
      technique and conventional mitral valve surgery (MVS). METHODS: Three hundred and
      nineteen patients who underwent MVS between April 2005 and December 2006 were
      enrolled in the study. While 125 patients underwent beating heart MVS (group 1),
      the conventional approach was used for 194 patients (group 2). Of those patients
      who underwent beating heart MVS, 75 underwent MVS without cross-clamping the
      aorta. Coronary sinus retroperfusion was used during surgery in the remaining 50
      patients. The right anterolateral thoracotomy was performed in nine out of the 29
      patients requiring re-operation, while resternotomy was performed in 20. RESULTS:
      No significant differences were shown between the groups in the preoperative
      period in terms of the Parsonnet mortality score, Ontario mortality score, and
      length of intensive care stay. However, there were significant differences with
      respect to EuroSCORE risk score, EuroSCORE mortality, and Parsonnet risk score,
      and length of hospital stay according to Ontario risk scoring. It was established
      that the patients in group 1 had a shorter length of hospital stay [group 1: six
      days (range, 4-37 days); group 2: 10 days (range, 4-62 days)]. Group 1 was
      observed to have shorter time periods when the groups were compared regarding
      operative time [group 1: 130 min (range, 100-270 min); group 2: 240 min (range,
      100-360 min)], cross-clamping (XCL) time [group 1: 27.5 min (range, 3-99 min);
      group 2: 60.5 min (range, 30-163 min)], and cardiopulmonary bypass time [group 1:
      57 min (range, 22-150 min); group 2: 90 min (range, 39-388 min)]. There were also
      significant differences in favor of group 1 in terms of postoperative need for
      inotropic support [group 1: 26 patients (16%); group 2: 68 patients (35%)].
      Although there were no statistically significant differences in the groups in
      terms of mortality rates according to the Parsonnet scoring system, with the
      exception of the moderate risk group, it was noted that the mortality rates in
      the beating heart group were lower. CONCLUSIONS: This study concluded that
      beating heart MVS can be performed successfully, particularly for patients at
      higher risk which will lead to increased morbidity and mortality in postoperative
      period.

PMID- 21177301
TI  - The 4th European Association for Cardio-Thoracic Surgery adult cardiac surgery
      database report.

PMID- 21177302
TI  - Intraluminal repair or conservative management of iatrogene posterior tracheal
      lacerations.

PMID- 21177303
TI  - A golden key can open any door of new protocol: the use of continuous digital
      measurement for postoperative air leak.

PMID- 21177304
TI  - Endovascular treatment of mycotic saccular aneurysms of the thoracic aorta.

PMID- 21177305
TI  - Aortic arch anomalies--persistent fifth aortic arch remnant.

PMID- 21177306
TI  - Bivariate random effects models for meta-analysis of comparative studies with
      binary outcomes: methods for the absolute risk difference and relative risk.
AB  - Multivariate meta-analysis is increasingly utilised in biomedical research to
      combine data of multiple comparative clinical studies for evaluating drug
      efficacy and safety profile. When the probability of the event of interest is
      rare, or when the individual study sample sizes are small, a substantial
      proportion of studies may not have any event of interest. Conventional meta
      analysis methods either exclude such studies or include them through ad hoc
      continuality correction by adding an arbitrary positive value to each cell of the
      corresponding 2 * 2 tables, which may result in less accurate conclusions.
      Furthermore, different continuity corrections may result in inconsistent
      conclusions. In this article, we discuss a bivariate Beta-binomial model derived
      from Sarmanov family of bivariate distributions and a bivariate generalised
      linear mixed effects model for binary clustered data to make valid inferences.
      These bivariate random effects models use all available data without ad hoc
      continuity corrections, and accounts for the potential correlation between
      treatment (or exposure) and control groups within studies naturally. We then
      utilise the bivariate random effects models to reanalyse two recent meta-analysis
      data sets.

PMID- 21177307
TI  - Green tea polyphenol EGCG blunts androgen receptor function in prostate cancer.
AB  - Androgen deprivation therapy is the major treatment for advanced prostate cancer
      (PCa). However, it is a temporary remission, and the patients almost inevitably
      develop hormone refractory prostate cancer (HRPC). HRPC is almost incurable,
      although most HRPC cells still express androgen receptor (AR) and depend on the
      AR for growth, making AR a prime drug target. Here, we provide evidence that
      epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, is a direct
      antagonist of androgen action. In silico modeling and FRET-based competition
      assay showed that EGCG physically interacts with the ligand-binding domain of AR
      by replacing a high-affinity labeled ligand (IC(50) 0.4 MUM). The functional
      consequence of this interaction was a decrease in AR-mediated transcriptional
      activation, which was due to EGCG mediated inhibition of interdomain N-C termini
      interaction of AR. Treatment with EGCG also repressed the transcriptional
      activation by a hotspot mutant AR (T877A) expressed ectopically as well as the
      endogenous AR mutant. As the physiological consequence of AR antagonism, EGCG
      repressed R1881-induced PCa cell growth. In a xenograft model, EGCG was found to
      inhibit AR nuclear translocation and protein expression. We also observed a
      significant down-regulation of androgen-regulated miRNA-21 and up-regulation of a
      tumor suppressor, miRNA-330, in tumors of mice treated with EGCG. Taken together,
      we provide evidence that EGCG functionally antagonizes androgen action at
      multiple levels, resulting in inhibition of PCa growth.

PMID- 21177308
TI  - Varicella zoster disease of the central nervous system: epidemiological,
      clinical, and laboratory features 10 years after the introduction of the
      varicella vaccine.
AB  - BACKGROUND: Since the introduction of live attenuated varicella zoster virus
      (VZV) vaccine in 1995 there has been a significant reduction in varicella
      incidence and its associated complications, but the impact on VZV-associated
      central nervous system (CNS) disease has not been assessed. METHODS: In this
      descriptive study we evaluated patients referred to the California Encephalitis
      Project from 1998 to 2009 with VZV PCR-positive cerebrospinal fluid (CSF).
      Epidemiological, clinical, and laboratory data were collected using a
      standardized case form. Specimens were genotyped using multi-single nucleotide
      polymorphism (SNP) analysis. RESULTS: Twenty-six specimens were genotyped from
      patients 12-85 years of age (median, 46 years). Clinical presentations included
      meningitis (50%), encephalitis (42%), and acute disseminated encephalomyelitis
      (ADEM) (8%). Only 11 patients (42%) had a concomitant herpes zoster rash.
      Genotype analysis identified 20 European Group (Clade1, Clade 3) strains; 4 Asian
      (Clade 2) strains, and 2 Mosaic Group (Clade 4, Clade VI) strains. One specimen
      was recognized as vaccine strain by identifying vaccine-associated SNPs.
      CONCLUSIONS: VZV continues to be associated with CNS disease, with meningitis
      being the most frequent clinical presentation. CNS VZV disease often presented
      without accompanying zoster rash. Sequencing data revealed multiple genotypes,
      including 1 vaccine strain detected in the CSF of a young patient with
      meningitis.

PMID- 21177309
TI  - Normalization of FoxP3(+) regulatory T cells in response to effective
      antiretroviral therapy.
AB  - Regulatory T cells (Tregs) blunt uncontrolled immune responses. In advanced human
      immunodeficiency virus (HIV) infection, the total number of Tregs is decreased,
      but the proportion of T cells with a regulatory phenotype is highly variable. We
      studied CD4(+)CD25(+)FoxP3(+) T cells from patients successfully treated with
      combination antiretroviral therapy (ART). The proportion of CD4(+)CD25(+)FoxP3(+)
      cells transiently increased and then decreased from a median of 13% at baseline
      to 5.1% at 48 weeks, similar to values in normal subjects. These data suggest
      that with effective therapy, the regulatory cell numbers normalize, and that the
      inflammatory signals driving their production may also abate.

PMID- 21177310
TI  - Sperm and oocyte donors' experiences of anonymous donation and subsequent contact
      with their donor offspring.
AB  - BACKGROUND: This study examined the motivations and experiences of anonymous
      donors who decide to make themselves open to contact with their donor offspring.
      METHODS: Online questionnaires were completed by 63 sperm donors and 11 oocyte
      donors recruited via the Donor Sibling Registry
      (http://www.donorsiblingregistry.com/), a US-based international registry that
      facilitates contact between donor-conceived offspring and their donors. RESULTS:
      Donors' main reasons for donating were financial payment and wanting to help
      others. Sperm donors had donated between 1 and 950 times (median = 100) and
      oocyte donors had donated between 1 and 5 times (median = 2). The majority of
      sperm donors and more than one-third of oocyte donors expressed concerns about
      having donated. These concerns were mainly about the well-being of any children
      conceived using their gametes and not being able to make contact with them. Most
      sperm and oocyte donors felt that it was important to know how many offspring had
      been born using their donation, and 51% of sperm donors and 46% of oocyte donors
      wanted identifying information. All of the donors who had contact with their
      donor offspring reported positive experiences and the majority continued to have
      regular contact. CONCLUSIONS: Although the sample may not be representative of
      all anonymous donors, this study highlights the importance of donors having
      access to information about their donor offspring and the positive consequences
      that may arise when contact is made.

PMID- 21177311
TI  - Serum anti-Mullerian hormone levels are negatively related to Follicular Output
      RaTe (FORT) in normo-cycling women undergoing controlled ovarian
      hyperstimulation.
AB  - BACKGROUND: Since in rodents anti-Mullerian hormone (AMH) has been shown to
      inhibit antral follicle responsiveness to FSH, we aimed at verifying whether a
      relationship exists between serum AMH levels and antral follicle responsiveness
      to exogenous FSH in normo-cycling women. METHODS: Serum AMH, estradiol (E(2)) and
      FSH levels were prospectively measured on cycle day 3 in patients undergoing
      controlled ovarian hyperstimulation (COH) with a time-release GnRH agonist and
      standardized FSH doses. In 162 patients, follicles were counted after pituitary
      suppression and before FSH administration (baseline; small antral follicles; 3-8
      mm), and on the day of hCG (dhCG; pre-ovulatory follicles; 16-22 mm). Antral
      follicle responsiveness to FSH was estimated by the Follicular Output RaTe
      (FORT), determined by the ratio pre-ovulatory follicle count on dhCG * 100/small
      antral follicle count at baseline. RESULTS: Serum AMH levels were positively
      correlated with the number of small antral follicles at baseline (r = 0.59; P <
      0.0001) and pre-ovulatory follicles on dhCG (r = 0.17; P < 0.04). Overall, FORT
      was 47.5 +/- 1.4% and failed to be influenced by the woman's age, BMI or basal
      E(2) and FSH level. Conversely, multiple regression analysis showed that FORT was
      negatively correlated with AMH levels (r = -0.30; P < 0.001), irrespective of
      duration of COH and total FSH dose. CONCLUSIONS: The percentage of follicles that
      effectively respond to FSH by reaching pre-ovulatory maturation is negatively and
      independently related to serum AMH levels. Although the mechanisms underlying
      this finding remain unclear, it is in keeping with the hypothesis that AMH
      inhibits follicle sensitivity to FSH.

PMID- 21177312
TI  - The effects of timing of intrauterine insemination in relation to ovulation and
      the number of inseminations on cycle pregnancy rate in common infertility
      etiologies.
AB  - BACKGROUND: Controlled ovarian hyperstimulation with intrauterine insemination
      (COH/IUI) is an established tool in medically assisted conception for many
      infertility factors. However, the proper timing of IUI after hCG trigger and the
      frequency of IUI are still debated. We aimed to examine the association between
      the cycle pregnancy rate (CPR) and: (i) single IUI timed at 36 +/- 2 h post-hCG
      (pre- or post-ovulation) (ii) the number of IUI (single or double) for pre
      ovulatory cases both aims in male, anovulatory and unexplained infertility.
      METHODS: The study included a total 1146 first-stimulated cycles in infertile
      couples due to male factor, anovulation or unexplained infertility. Cycles were
      stimulated by clomiphine citrate (CC) or sequential CC-hMG or hMG and monitored
      by transvaginal ultrasound. When the leading follicle reached >= 18 mm mean
      diameter, 10000 IU hCG was given to trigger ovulation and IUI was timed for 36 +/
      2 h later. Semen was processed and ovulation was checked at the time of IUI.
      Post-ovulatory cases received single IUI, while pre-ovulatory cases were
      sequentially randomized to receive either single or double IUI. The end-point of
      the cycle was CPR. RESULTS: Overall CPR in the whole cohort was 10.1%. When
      ovulation was present before IUI, CPR was 11.7% compared with 6.7% when ovulation
      was absent [OR (95% CI): 1.85 (1.12-3.06), P = 0.015]. When this OR was computed
      according to infertility etiology, it was 1.26 (0.52-2.95) (P = 0.82) for male
      factor infertility and 2.24 (1.23-4.08) (P = 0.007) for non-male factor
      infertility. Comparing the CPR for double versus single IUI in pre-ovulatory
      cases, the OR for all cycles was 1.9 (0.76-4.7) (P = 0.22), but according to
      etiology, it was 4.667 (0.9-24.13) (P = 0.06) in male factor and 1.2 (0.43-3.33)
      (P = 0.779) for non-male factors. CONCLUSIONS: Single IUI timed post-ovulation
      gives a better CPR when compared with single pre-ovulation IUI for non-male
      infertility, whereas for male factors, pre-ovulation, double IUI gives a better
      CPR when compared with single IUI.

PMID- 21177313
TI  - Dietary fat consumption and endometriosis risk.

PMID- 21177315
TI  - Meta-analysis of three polymorphisms in the steroid-5-alpha-reductase, alpha
      polypeptide 2 gene (SRD5A2) and risk of prostate cancer.
AB  - The steroid-5-alpha-reductase, alpha polypeptide 2 (SRD5A2) gene plays a crucial
      role in androgen metabolism pathway in human prostate. It encodes SRD5A2 enzyme,
      which catalyses testosterone to dihydrotestosterone (DHT). DHT is the main active
      structure binding with androgen receptor (AR). After the activation of AR, it
      further regulates a series of target genes in androgen metabolism pathway.
      However, no clear consensus has been reached on the association between the
      SRD5A2 V89L, A49T and TA repeat polymorphisms and prostate cancer (PCa) risk.
      Thus, we performed a meta-analysis of 31 association studies with 14,726 PCa
      cases and 15,802 controls. We found no association between PCa and 89L compared
      with 89V allele [odds ratio (OR) = 1.02, 95% confidence interval (CI) 0.98-1.06,
      P(heterogeneity) = 0.44]. The 49T allele showed a significantly elevated effect
      on the high stage (Stages III-IV) of PCa risk both under the dominant genetic
      model (OR = 2.13, 95% CI 1.44-3.15, P(heterogeneity) = 0.65) and in the contrast
      T versus A allele (OR = 2.06, 95% CI 1.41-3.02, P(heterogeneity) = 0.69). There
      was a significantly decreased association between PCa and long TA repeat as
      compared versus short TA repeat (OR = 0.86, 95% CI 0.74-1.00, P(heterogeneity) =
      0.79). No significant between-study heterogeneity was found in all subjects under
      four genetic models (dominant model, recessive model, allele comparison and
      homozygosity comparison) for these three polymorphisms, respectively, so the
      fixed effects model was used to pool the result. Our result indicated that
      carriers of 49T might improve the risk of PCa in higher stages (Stages III-IV),
      carriers of long TA repeat might decrease the risk of PCa and 89L may not be an
      important risk factor for PCa. However, due to the limited sample sizes, this
      meta-analysis did not achieve sufficiently conclusive results. Still more well
      designed studies should be performed to clarify the role of these three
      polymorphisms in the development of PCa.

PMID- 21177316
TI  - Estimation of population divergence times from non-overlapping genomic sequences:
      examples from dogs and wolves.
AB  - Despite recent technological advances in DNA sequencing, incomplete coverage
      remains to be an issue in population genomics, in particular for studies that
      include ancient samples. Here, we describe an approach to estimate population
      divergence times for non-overlapping sequence data that is based on probabilities
      of different genealogical topologies under a structured coalescent model. We show
      that the approach can be adapted to accommodate common problems such as
      sequencing errors and postmortem nucleotide misincorporations, and we use
      simulations to investigate biases involved with estimating genealogical
      topologies from empirical data. The approach relies on three reference genomes
      and should be particularly useful for future analysis of genomic data that
      comprise of nonoverlapping sets of sequences, potentially from different points
      in time. We applied the method to shotgun sequence data from an ancient wolf
      together with extant dogs and wolves and found striking resemblance to previously
      described fine-scale population structure among dog breeds. When comparing modern
      dogs to four geographically distinct wolves, we find that the divergence time
      between dogs and an Indian wolf is smallest, followed by the divergence times to
      a Chinese wolf and a Spanish wolf, and a relatively long divergence time to an
      Alaskan wolf, suggesting that the origin of modern dogs is somewhere in Eurasia,
      potentially southern Asia. We find that less than two-thirds of all loci in the
      boxer and poodle genomes are more similar to each other than to a modern gray
      wolf and that--assuming complete isolation without gene flow--the divergence time
      between gray wolves and modern European dogs extends to 3,500 generations before
      the present, corresponding to approximately 10,000 years ago (95% confidence
      interval [CI]: 9,000-13,000). We explicitly study the effect of gene flow between
      dogs and wolves on our estimates and show that a low rate of gene flow is
      compatible with an even earlier domestication date ~30,000 years ago (95% CI:
      15,000-90,000). This observation is in agreement with recent archaeological
      findings and indicates that human behavior necessary for domestication of wild
      animals could have appeared much earlier than the development of agriculture.

PMID- 21177317
TI  - Lithium-induced hyperthyroidism, thyrotoxicosis and mania: a case report.

PMID- 21177318
TI  - Diagnosis of melanoma under concomitant natalizumab therapy.

PMID- 21177319
TI  - CD46 in a Spanish cohort of multiple sclerosis patients: genetics, mRNA
      expression and response to interferon-beta treatment.
AB  - BACKGROUND: In a prior study of our group we found an up-regulation of CD46
      expression in a cohort of Spanish multiple sclerosis (MS) patients. OBJECTIVE: To
      evaluate the potential role of CD46 in the response to interferon-beta treatment
      in MS patients through the analysis of five tagging single nucleotide
      polymorphisms (SNPs) and measurement of mRNA. METHODS: A total of 406 MS patients
      and 513 control patients were analysed for five SNPs at the CD46 locus.
      Furthermore, 163 MS patients and 163 matched control patients were analysed by RT
      PCR for the CD46 mRNA expression in three blood samples (basal, and at 6 and 12
      months of interferon-beta treatment) collected in the course of a 1-year follow
      up. RESULTS: Two genotypes of rs2724385 polymorphism (AT and TT) could be markers
      of response to interferon-beta therapy in MS patients (p=0.007 and p=0.006,
      respectively). Furthermore, the frequency of interferon-beta responders was 44.4%
      (32/72) in MS patients with an increased CD46 mRNA expression, vs. 65.9% (60/91)
      in patients with a decreased CD46 mRNA expression (p=0.006). CONCLUSION: The
      present study shows that CD46 could be associated with the response to interferon
      beta therapy; however, the genetic results should be replicated in an independent
      cohort and further studies are needed to confirm the role of CD46.

PMID- 21177320
TI  - Magnetic resonance imaging as surrogate for clinical endpoints in multiple
      sclerosis: data on novel oral drugs.
AB  - Recent studies have provided evidence for using magnetic resonance imaging (MRI)
      active lesions as surrogate for relapses and disability progression in multiple
      sclerosis (MS). However, the validity of MRI metrics as surrogate endpoints in MS
      is controversial. Furthermore, the extrapolation of previous results to novel
      therapies is not warranted. We tested here the validity of MRI surrogacy in MS
      studies on recently published trials of oral drugs. The 92% of observed effects
      of oral drugs on clinical outcomes resulted close to those predicted by MRI
      active lesions. This further validates MRI surrogacy in MS, with important
      implications for future trials planning.

PMID- 21177321
TI  - An approach to natalizumab hypersensitivity: a case series of induction of
      tolerance.
AB  - Induction of tolerance protocols have been applied successfully to manage
      allergic reactions to many medications. Hypersensitivity reactions to natalizumab
      (TYSABRI(r)) have been recognized as a growing problem. In circumstances where a
      hypersensitivity reaction to a medication has occurred, but no suitable
      alternative exists, drug induction of tolerance protocols may be considered. Drug
      induction of tolerance protocols were performed in three patients with prior
      hypersensitivity reactions to natalizumab. All three patients tolerated the
      protocol without adverse reactions, allowing for the safe reintroduction of
      natalizumab. To conclude, this case series demonstrates success with an induction
      of tolerance procedure to a highly effective biological agent for multiple
      sclerosis, in patients with allergic reactions to natalizumab.

PMID- 21177322
TI  - HLA-DR allele polymorphism and multiple sclerosis in Chinese populations: a meta
      analysis.
AB  - BACKGROUND: The association of human leukocyte antigen (HLA) genes and multiple
      sclerosis (MS) has been extensively investigated in Caucasians, but less so in
      Oriental races such as Chinese. OBJECTIVES: To review studies on association of
      HLA class II alleles with MS in the Chinese population. METHODS: An extensive
      search for published studies up to June 2010 was performed in the electronic
      databases. The meta-analysis facilities in the NCSS statistical package were
      utilized to analyze the findings in these studies. The odds ratios (ORs) of HLA
      DR allele distributions in MS were analyzed against controls. RESULTS: Eleven
      case-control studies were identified: nine genotyping and two serotyping studies.
      Six genotyping studies were suitable for HLA-DRB1 allele meta-analysis, which
      showed that HLA-DRB1*15 was associated with risk of MS in the combined group (308
      cases and 407 controls; OR 1.39) while the HLA-DRB1*09 and HLA-DRB1*0901 alleles
      were protective. When the equivalent serotypes in these six studies were combined
      with the results from the two serotyping studies (431 cases and 652 controls) for
      a meta-analysis of HLA-DR serotypes, HLA-DR2 was a risk factor (OR 1.63) and HLA
      DR9 was strongly protective in the combined group (OR 0.64). CONCLUSIONS:
      Although limited data are available, our meta-analysis suggests that HLA
      DR2/DRB1*15 are also associated with risk of MS in the Chinese population but
      less strongly so than in Western MS populations, whereas HLA-DR9 alleles appear
      to confer resistance in this population.

PMID- 21177323
TI  - A functional magnetic resonance proof of concept pilot trial of cognitive
      rehabilitation in multiple sclerosis.
AB  - BACKGROUND: Cognitive impairment is frequent in multiple sclerosis (MS) and lacks
      effective treatment. Cognitive rehabilitation is widely applied in
      neurorehabilitation settings. Functional magnetic resonance imaging (fMRI) may
      help in investigating changes in brain activity and provide a tool to assess the
      efficacy of rehabilitation. AIM: To investigate the effect on brain activity as
      measured by fMRI of a cognitive rehabilitation programme in patients with MS and
      cognitive impairment. METHOD: Fifteen patients with MS and cognitive impairment
      and five healthy subjects were recruited. Neuropsychological assessments were
      performed in patients with MS at study entry and after rehabilitation to assess
      cognitive changes. fMRI scans were performed at week -5 (baseline), week 0
      (immediately before rehabilitation) and week 5 (immediately after
      rehabilitation). The fMRI paradigm was the Paced Auditory Serial Addition Test
      (PASAT). The cognitive rehabilitation programme was composed of 15 computer-aided
      drill and practice sessions and five non-computer-aided cognitive stimulation
      group sessions (over 5 weeks). Strict guidelines ensured comparability of all
      rehabilitation interventions. RESULTS: Patients had increased brain fMRI activity
      after rehabilitation in several cerebellar areas when compared with healthy
      subjects. After rehabilitation, patients had significantly improved their
      performance on the backward version of the Digit Span Test (p = 0.007) and on a
      composite score of neuropsychological outcomes (p = 0.009). CONCLUSION: The
      results of the present study indicate that this cognitive rehabilitation
      programme increases brain activity in the cerebellum of cognitively impaired
      patients with MS. The role of fMRI in the assessment of neurorehabilitation
      schemes warrants further investigation.

PMID- 21177324
TI  - CD4+T-bet+, CD4+pSTAT3+ and CD8+T-bet+ T cells accumulate in peripheral blood
      during NZB treatment.
AB  - Circulating T cells and monocytes expressing T-bet, pSTAT1 and pSTAT3 increase in
      relapsing-remitting multiple sclerosis (RRMS) during relapse. Natalizumab (NZB)
      is an effective drug in RRMS, but exacerbation of the disease after its
      discontinuation has been described in some patients. The aim of this research was
      to study the effect of NZB treatment on circulating lymphomonocyte subpopulations
      expressing T-bet, pSTAT1, pSTAT3 and CD4+CD25+Foxp3+ regulatory T cells. Flow
      cytometry was used to evaluate the percentages of circulating CD4+ and CD8+ T
      cells, CD14+ monocytes and B cells expressing T-bet, pSTAT1, and pSTAT3, and
      CD4+CD25+Foxp3+ regulatory T cells from RRMS patients before and after 6-12 NZB
      infusions. In NZB-treated RRMS patients, the percentages of CD4+pSTAT1+ and
      CD8+pSTAT1+ T cells, CD14+pSTAT1+ monocytes, CD4+T-bet+, CD8+T-bet+ and
      CD4+pSTAT3+ T cells and CD14+pSTAT3+ monocytes increased after 12 drug infusions
      and were similar to those observed in untreated relapsing RRMS patients.
      Otherwise in vitro NZB exposure of peripheral blood mononuclear cells from
      untreated RRMS patients and controls had no effect. It was concluded that NZB
      treatment determines an accumulation of CD4+pSTAT1+, CD8+pSTAT1+, CD4+T-bet+,
      CD8+T-bet+ and CD4+STAT3+ T cells in peripheral blood that may account for the
      exacerbation of the disease observed in some patients after the discontinuation
      of the drug.

PMID- 21177325
TI  - Lesion probability mapping to explain clinical deficits and cognitive performance
      in multiple sclerosis.
AB  - BACKGROUND: Lesion dissemination in time and space represents a key feature and
      diagnostic marker of multiple sclerosis (MS). The correlation between magnetic
      resonance imaging (MRI) lesion load and disability is only modest, however.
      Strategic lesion location might at least partially account for this 'clinico
      radiologic paradox'. OBJECTIVES: Here we used a non-parametric permutation-based
      approach to map lesion location probability based on MS lesions identified on T2
      weighted MRI. We studied 121 patients with clinically isolated syndrome,
      relapsing-remitting or secondary progressive MS and correlated these maps to
      assessments of neurologic and cognitive functions. RESULTS: The Expanded
      Disability Status Scale correlated with bilateral periventricular lesion location
      (LL), and sensory and coordination functional system deficits correlated with
      lesion accumulation in distinct anatomically plausible regions, i.e. thalamus and
      middle cerebellar peduncule. Regarding cognitive performance, decreased verbal
      fluency correlated with left parietal LL comprising the putative superior
      longitudinal fascicle. Delayed spatial recall correlated with _amygdalar, _left
      frontal and parietal LL. Delayed selective reminding correlated with bilateral
      frontal and temporal LL. However, only part of the spectrum of cognitive and
      neurological problems encountered in our cohort could be explained by specific
      lesion location. CONCLUSIONS: Lesion probability mapping supports the association
      of specific lesion locations with symptom development in MS, but only to limited
      extent.

PMID- 21177326
TI  - Kinetics and incidence of anti-natalizumab antibodies in multiple sclerosis
      patients on treatment for 18 months.
AB  - Natalizumab is a monoclonal antibody shown to be highly effective in the
      treatment of relapsing-remitting multiple sclerosis (RRMS). Patients treated with
      natalizumab can develop antibodies directed against this agent that may affect
      the efficacy and safety of the drug. In this observational study, the kinetics of
      the appearance and the incidence of anti-natalizumab antibodies were followed
      prospectively for 18 months in a cohort of 64 consecutive patients treated with
      natalizumab for relapsing MS. Blood samples were drawn immediately before
      starting natalizumab therapy and each month afterwards. The presence of
      antibodies against natalizumab was assessed by enzyme-linked immunosorbent assay
      (ELISA) in all patients. Anti-natalizumab antibodies were detected in nine
      (14.1%) natalizumab-treated patients, three (4.68%) of whom were transiently
      positive while six (9.37%) were persistently positive (these patients
      discontinued natalizumab). All positive titres were observed during the first 4
      months of treatment. One patient with a hypersensitivity reaction also had
      persistent antibodies. We conclude that antibodies against natalizumab develop
      early, within the first 6 months of therapy with natalizumab. Although no
      antibodies were detected after 4 months of therapy in this particular study, this
      does not rule out their development later on in exceptional cases.

PMID- 21177327
TI  - Familial multiple sclerosis: does consanguinity have a role?
AB  - Parental consanguinity (PC) may be a risk factor for familial multiple sclerosis
      (FMS) throughout inbred communities. The objective of this report was to estimate
      prevalence of FMS and rate of PC among FMS versus non-FMS patients. All Saudi MS
      patients were identified from our registry. The history of PC was analyzed as a
      case-control study. In total 141 MS patients were identified. Of these, 30 (21%)
      reported having at least one affected relative, 37.6% reported PC and 16%
      presented first-degree PC. In addition, FMS patients were more likely than non
      FMS patients to report PC. In conclusion, FMS is prevalent among Saudi MS
      patients. MS patients with a history of PC were more likely to have FMS,
      suggesting a potential role of consanguinity.

PMID- 21177328
TI  - Improvements in the reconstruction of time-varying gene regulatory networks:
      dynamic programming and regularization by information sharing among genes.
AB  - METHOD: Dynamic Bayesian networks (DBNs) have been applied widely to reconstruct
      the structure of regulatory processes from time series data, and they have
      established themselves as a standard modelling tool in computational systems
      biology. The conventional approach is based on the assumption of a homogeneous
      Markov chain, and many recent research efforts have focused on relaxing this
      restriction. An approach that enjoys particular popularity is based on a
      combination of a DBN with a multiple changepoint process, and the application of
      a Bayesian inference scheme via reversible jump Markov chain Monte Carlo
      (RJMCMC). In the present article, we expand this approach in two ways. First, we
      show that a dynamic programming scheme allows the changepoints to be sampled from
      the correct conditional distribution, which results in improved convergence over
      RJMCMC. Second, we introduce a novel Bayesian clustering and information sharing
      scheme among nodes, which provides a mechanism for automatic model complexity
      tuning. RESULTS: We evaluate the dynamic programming scheme on expression time
      series for Arabidopsis thaliana genes involved in circadian regulation. In a
      simulation study we demonstrate that the regularization scheme improves the
      network reconstruction accuracy over that obtained with recently proposed
      inhomogeneous DBNs. For gene expression profiles from a synthetically designed
      Saccharomyces cerevisiae strain under switching carbon metabolism we show that
      the combination of both: dynamic programming and regularization yields an
      inference procedure that outperforms two alternative established network
      reconstruction methods from the biology literature. AVAILABILITY AND
      IMPLEMENTATION: A MATLAB implementation of the algorithm and a supplementary
      paper with algorithmic details and further results for the Arabidopsis data can
      be downloaded from: http://www.statistik.tu-dortmund.de/bio2010.html.

PMID- 21177329
TI  - The intriguing nature of microsporidian genomes.
AB  - Microsporidia are a group of highly adapted unicellular fungi that are known to
      infect a wide range of animals, including humans and species of great economic
      importance. These organisms are best known for their very simple cellular and
      genomic features, an adaptive consequence of their obligate intracellular
      parasitism. In the last decade, the acquisition of a large amount of genomic and
      transcriptomic data from several microsporidian species has greatly improved our
      understanding of the consequences of a purely intracellular lifestyle. In
      particular, genome sequence data from these pathogens has revealed how obligate
      intracellular parasitism can result in radical changes in the composition and
      structure of nuclear genomes and how these changes can affect cellular and
      evolutionary mechanisms that are otherwise well conserved among eukaryotes. This
      article reviews our current understanding of the genome content and structure of
      microsporidia, discussing their evolutionary origin and cataloguing the
      mechanisms that have often been involved in their extreme reduction.

PMID- 21177330
TI  - CDKN1B V109G polymorphism a new prognostic factor in sporadic medullary thyroid
      carcinoma.
AB  - CONTEXT: CDKN1B encodes the cyclin-dependent kinase inhibitor p27Kip1 and is
      mutated in multiple endocrine neoplasia-like syndromes. CDKN1B also harbors
      single nucleotide polymorphisms; the T/G transversion at nucleotide 326 (the
      V109G variant) has been reported to be protective in breast, hereditary prostate,
      and pancreatic tumors. Association of CDNK1B mutations or polymorphisms with
      sporadic medullary thyroid carcinoma (MTC) has not been investigated yet.
      OBJECTIVE AND DESIGN: We screened germline DNA from 84 patients affected by
      sporadic MTC and 90 healthy age- and gender-matched controls for CDKN1B mutations
      or polymorphisms by PCR amplification and sequencing of the amplicons. We also
      tested all germline and 50 tumor tissue DNA for RET proto-oncogene mutations.
      Computed tomography, ultrasound scans, and serum calcitonin were carried out
      before surgery and during the follow-up and associated with CDKN1B polymorphism
      and disease remission. RESULTS: The T/G transversion at nucleotide 326 was the
      only DNA variation detected. The overall frequency of the T/G and G/G alleles in
      combination was 46.4%. This variant (V109G) was correlated with post-operative
      calcitonin levels in the normal range and biochemical remission. Conversely, the
      wild-type (T/T) allele was associated with post-operative calcitonin levels above
      normal and a higher risk to develop clinical recurrence and distant metastases.
      Somatic RET mutations were significantly associated with a more aggressive
      behavior especially in wild-type allele-bearing patients. CONCLUSIONS:
      Collectively, in sporadic MTC, the CDKN1B V109G polymorphism correlates with a
      more favorable disease progression than the wild-type allele and might be
      considered a new promising prognostic marker.

PMID- 21177331
TI  - Dermatan sulfate epimerase 2 is the predominant isozyme in the formation of the
      chondroitin sulfate/dermatan sulfate hybrid structure in postnatal developing
      mouse brain.
AB  - Chondroitin sulfate (CS) and dermatan sulfate (DS) are expressed in significant
      amounts in the brain and play important roles in the development of the central
      nervous system in mammals. CS and DS structures are often found in a single CS/DS
      hybrid chain. The l-iduronic acid (IdoA)-containing domain, which defines a DS
      type domain, appears key to the biological functions of the CS/DS hybrid chain.
      In this study, to clarify the distribution of the DS-type structure in the brain
      during development, the expression patterns of DS epimerase 1 (DS-epi1) and DS
      epi2, both of which convert d-glucuronic acid into IdoA, were investigated by in
      situ hybridization. DS-epi2 was ubiquitously expressed in the developing brain
      after birth, whereas the expression of DS-epi1 was faint and obscure at all
      developmental stages. Quantitative real-time polymerase chain reaction revealed
      the expression of DS-epi2 to be higher than that of DS-epi1 throughout
      development, suggesting that DS-epi2 but not DS-epi1 is mostly expressed in the
      brain and plays key roles in the epimerization of CS/DS during its biosynthesis.
      Moreover, an analysis of the disaccharides of CS/DS demonstrated significant
      amounts of IdoA-containing iD units [IdoA(2S)-GalNAc(6S)] and iB units [IdoA(2S)
      GalNAc(4S)], where 2S, 4S and 6S stand for 2-O-, 4-O- and 6-O-sulfate,
      respectively, in every region of the brain examined. The proportion of these
      units in cerebellar CS/DS was greatly altered during postnatal development. These
      results suggest that the IdoA-containing structures in the developing brain are
      mainly produced by the actions of DS-epi2 and play crucial roles in postnatal
      development.

PMID- 21177333
TI  - Safety of rituximab therapy during twins' pregnancy.

PMID- 21177332
TI  - AthaMap-assisted transcription factor target gene identification in Arabidopsis
      thaliana.
AB  - The AthaMap database generates a map of potential transcription factor binding
      sites (TFBS) and small RNA target sites in the Arabidopsis thaliana genome. The
      database contains sites for 115 different transcription factors (TFs). TFBS were
      identified with positional weight matrices (PWMs) or with single binding sites.
      With the new web tool 'Gene Identification', it is possible to identify potential
      target genes for selected TFs. For these analyses, the user can define a region
      of interest of up to 6000 bp in all annotated genes. For TFBS determined with
      PWMs, the search can be restricted to high-quality TFBS. The results are
      displayed in tables that identify the gene, position of the TFBS and, if
      applicable, individual score of the TFBS. In addition, data files can be
      downloaded that harbour positional information of TFBS of all TFs in a region
      between -2000 and +2000 bp relative to the transcription or translation start
      site. Also, data content of AthaMap was increased and the database was updated to
      the TAIR8 genome release. Database URL: http://www.athamap.de/gene_ident.php.

PMID- 21177334
TI  - Heat shock protein 90 maintains the tumour-like character of rheumatoid synovial
      cells by stabilizing integrin-linked kinase, extracellular signal-regulated
      kinase and protein kinase B.
AB  - OBJECTIVE: To clarify the contribution of heat shock protein 90 (HSP90) to the
      pathogenesis of RA, we studied the effects of geldanamycin (GA), an inhibitor of
      HSP90, on excessive cellular extension and resistance to apoptosis induction of
      rheumatoid synovial cells. METHODS: Expression of integrin-alpha5beta1 and
      integrin-linked kinase (ILK) in synovial cells was determined by western blot.
      The peripheral localization of ILK, reorganization of F-actin, complex formation
      of ILK with particularly interesting new cysteine-histidine protein (PINCH) and
      alpha-parvin, and activation of Rac/cdc42 in synovial cells were examined by
      using immunohistochemistry and immunoprecipitation. Apoptosis induction by GA
      treatment was analysed by nuclear staining, cell proliferation assay and western
      blot of caspase. Effects of GA on mitogen-activated protein kinase (MAPK), PI
      3K/protein kinase B (Akt) pathway, mitochondrial Bcl-2 pathway and activation of
      nuclear factor-kappaB (NF-kappaB) were examined by western blot and ELISA.
      RESULTS: HSP90 was overexpressed in synovial cells while GA decreased the
      expression of integrin-alpha5beta1 and ILK. The peripheral localization of ILK,
      reorganization of F-actin, complex formation of ILK with PINCH and alpha-parvin,
      and activation of Rac/cdc42 in synovial cells were all inhibited by GA treatment.
      We found that HSP90 stabilized and regulated the MAPK and PI-3K/Akt pathway,
      thereby inhibiting HSP90-potentiated synovial apoptosis by stimulating caspases
      and the mitochondrial Bcl-2 pathway on the one hand and inhibiting the activation
      of NF-kappaB on the other. CONCLUSION: The contribution of HSP90 is important in
      the pathogenesis of RA that potentiates a tumour-like synovial overgrowth by
      stabilizing ILK, extracellular signal-regulated kinase and Akt.

PMID- 21177335
TI  - The paradoxical world of protein O-GlcNAcylation: a novel effector of
      cardiovascular (dys)function.

PMID- 21177336
TI  - CD36: the common soil for inflammation in obesity and atherosclerosis?

PMID- 21177337
TI  - Single-cell whole-genome amplification technique impacts the accuracy of SNP
      microarray-based genotyping and copy number analyses.
AB  - Methods of comprehensive microarray-based aneuploidy screening in single cells
      are rapidly emerging. Whole-genome amplification (WGA) remains a critical
      component for these methods to be successful. A number of commercially available
      WGA kits have been independently utilized in previous single-cell microarray
      studies. However, direct comparison of their performance on single cells has not
      been conducted. The present study demonstrates that among previously published
      methods, a single-cell GenomePlex WGA protocol provides the best combination of
      speed and accuracy for single nucleotide polymorphism microarray-based copy
      number (CN) analysis when compared with a REPLI-g- or GenomiPhi-based protocol.
      Alternatively, for applications that do not have constraints on turnaround time
      and that are directed at accurate genotyping rather than CN assignments, a REPLI
      g-based protocol may provide the best solution.

PMID- 21177338
TI  - First-line temozolomide chemotherapy in progressive low-grade astrocytomas after
      radiotherapy: molecular characteristics in relation to response.
AB  - Only a few studies examined the effect of temozolomide (TMZ) in recurrent low
      grade astrocytoma (LGA) after surgery, none of which included a homogeneous and
      sufficiently sized group of patients with progression after radiotherapy (RT). We
      evaluated a cohort of 58 patients treated with TMZ for progression after RT of a
      previous LGA and investigated the relation between outcome and mutations in the
      IDH1, IDH2, and TP53 genes, O6-methylguanine-methyltransferase (MGMT) promoter
      methylation, trisomy of chromosome 7, and loss of chromosomes 1p and 19q. All
      patients received first-line TMZ 200 mg/m2/day on days 1-5 every 4 weeks for a
      progressive LGA with a contrast-enhancing lesion on MRI after RT. Six months
      progression-free survival (PFS) was 67%, and the median overall survival was 14
      months. An objective response was obtained in 54%. TP53 mutations and loss of
      chromosome 19q showed a borderline association with PFS, but none of the other
      molecular characteristics were correlated with the outcome to TMZ. Both a
      methylated MGMT promoter gene and IDH1 mutations were found in 86% of the tumor
      samples. A correlation was found between IDH1 mutations and MGMT promoter
      methylation (P < .001). Neither MGMT promoter methylation nor IDH1 mutations
      correlated with PFS, but the interval between the very first symptom of the LGA
      and the start of the TMZ was significantly longer in the patients with IDH1
      mutations (P = .01) and a methylated MGMT promoter (P = .02). We conclude that
      MGMT promoter methylation and IDH1 mutations seem to predict survival from the
      time of diagnosis, but not PFS to TMZ.

PMID- 21177339
TI  - An interview with Ben Scheres by Kathryn Senior.

PMID- 21177341
TI  - Small micromeres contribute to the germline in the sea urchin.
AB  - Many indirect developing animals create specialized multipotent cells in early
      development to construct the adult body and perhaps to hold the fate of the
      primordial germ cells. In sea urchin embryos, small micromeres formed at the
      fifth division appear to be such multipotent cells: they are relatively quiescent
      in embryos, but contribute significantly to the coelomic sacs of the larvae, from
      which the major tissues of the adult rudiment are derived. These cells appear to
      be regulated by a conserved gene set that includes the classic germline lineage
      genes vasa, nanos and piwi. In vivo lineage mapping of the cells awaits genetic
      manipulation of the lineage, but previous research has demonstrated that the
      germline is not specified at the fourth division because animals are fertile even
      when micromeres, the parent blastomeres of small micromeres, are deleted. Here,
      we have deleted small micromeres at the fifth division and have raised the
      resultant larvae to maturity. These embryos developed normally and did not
      overexpress Vasa, as did embryos from a micromere deletion, implying the
      compensatory gene regulatory network was not activated in small micromere-deleted
      embryos. Adults from control and micromere-deleted embryos developed gonads and
      visible gametes, whereas small micromere-deleted animals formed small gonads that
      lacked gametes. Quantitative PCR results indicate that small micromere-deleted
      animals produce background levels of germ cell products, but not specifically
      eggs or sperm. These results suggest that germline specification depends on the
      small micromeres, either directly as lineage products, or indirectly by signaling
      mechanisms emanating from the small micromeres or their descendants.

PMID- 21177340
TI  - Developmental regulation of axon branching in the vertebrate nervous system.
AB  - During nervous system development, axons generate branches to connect with
      multiple synaptic targets. As with axon growth and guidance, axon branching is
      tightly controlled in order to establish functional neural circuits, yet the
      mechanisms that regulate this important process are less well understood. Here,
      we review recent advances in the study of several common branching processes in
      the vertebrate nervous system. By focusing on each step in these processes we
      illustrate how different types of branching are regulated by extracellular cues
      and neural activity, and highlight some common principles that underlie the
      establishment of complex neural circuits in vertebrate development.

PMID- 21177342
TI  - The Cdc14B phosphatase contributes to ciliogenesis in zebrafish.
AB  - Progression through the cell cycle relies on oscillation of cyclin-dependent
      kinase (Cdk) activity. One mechanism for downregulating Cdk signaling is to
      activate opposing phosphatases. The Cdc14 family of phosphatases counteracts Cdk1
      phosphorylation in diverse organisms to allow proper exit from mitosis and
      cytokinesis. However, the role of the vertebrate CDC14 phosphatases, CDC14A and
      CDC14B, in re-setting the cell for interphase remains unclear. To understand
      Cdc14 function in vertebrates, we cloned the zebrafish cdc14b gene and used
      antisense morpholino oligonucleotides and an insertional mutation to inhibit its
      function during early development. Loss of Cdc14B function led to an array of
      phenotypes, including hydrocephaly, curved body, kidney cysts and left-right
      asymmetry defects, reminiscent of zebrafish mutants with defective cilia. Indeed,
      we report that motile and primary cilia were shorter in cdc14b-deficient embryos.
      We also demonstrate that Cdc14B function in ciliogenesis requires its phosphatase
      activity and can be dissociated from its function in cell cycle control. Finally,
      we propose that Cdc14B plays a role in the regulation of cilia length in a
      pathway independent of fibroblast growth factor (FGF). This first study of a loss
      of function of a Cdc14 family member in a vertebrate organism reveals a new role
      for Cdc14B in ciliogenesis and consequently in a number of developmental
      processes.

PMID- 21177343
TI  - Dishevelled-associated activator of morphogenesis 1 (Daam1) is required for heart
      morphogenesis.
AB  - Dishevelled-associated activator of morphogenesis 1 (Daam1), a member of the
      formin protein family, plays an important role in regulating the actin
      cytoskeleton via mediation of linear actin assembly. Previous functional studies
      of Daam1 in lower species suggest its essential role in Drosophila trachea
      formation and Xenopus gastrulation. However, its in vivo physiological function
      in mammalian systems is largely unknown. We have generated Daam1-deficient mice
      via gene-trap technology and found that Daam1 is highly expressed in developing
      murine organs, including the heart. Daam1-deficient mice exhibit embryonic and
      neonatal lethality and suffer multiple cardiac defects, including ventricular
      noncompaction, double outlet right ventricles and ventricular septal defects. In
      vivo genetic rescue experiments further confirm that the lethality of Daam1
      deficient mice results from the inherent cardiac abnormalities. In-depth analyses
      have revealed that Daam1 is important for regulating filamentous actin assembly
      and organization, and consequently for cytoskeletal function in cardiomyocytes,
      which contributes to proper heart morphogenesis. Daam1 is also found to be
      important for proper cytoskeletal architecture and functionalities in embryonic
      fibroblasts. Biochemical analyses indicate that Daam1 does not regulate
      cytoskeletal organization through RhoA, Rac1 or Cdc42. Our study highlights a
      crucial role for Daam1 in regulating the actin cytoskeleton and tissue
      morphogenesis.

PMID- 21177344
TI  - Hindbrain patterning requires fine-tuning of early krox20 transcription by
      Sprouty 4.
AB  - Vertebrate hindbrain segmentation is an evolutionarily conserved process that
      involves a complex interplay of transcription factors and signalling pathways.
      Fibroblast growth factor (FGF) signalling plays a major role, notably by
      controlling the expression of the transcription factor Krox20 (Egr2), which is
      required for the formation and specification of two segmental units: rhombomeres
      (r) 3 and 5. Here, we explore the molecular mechanisms downstream of FGF
      signalling and the function of Sprouty 4 (Spry4), a negative-feedback regulator
      of this pathway, in zebrafish. We show that precise modulation of FGF signalling
      by Spry4 is required to determine the appropriate onset of krox20 transcription
      in r3 and r5 and, ultimately, rhombomere size in the r3-r5 region. FGF signalling
      acts by modulating the activity of krox20 initiator enhancer elements B and C; in
      r5, we show that this regulation is mediated by direct binding of the
      transcription factor MafB to element B. By contrast, FGF signalling does not
      control the krox20 autoregulatory element A, which is responsible for
      amplification and maintenance of krox20 expression. Therefore, early krox20
      transcription sets the blueprint for r3-r5 patterning. This work illustrates the
      necessity for fine-tuning in a common and fundamental patterning process, based
      on a bistable cell-fate choice involving the coupling of an extracellular
      gradient with a positive-feedback loop. In this mode of patterning, precision and
      robustness can be achieved by the introduction of a negative-feedback loop,
      which, in the hindbrain, is mediated by Spry4.

PMID- 21177345
TI  - Bcl-2 proteins and autophagy regulate mitochondrial dynamics during programmed
      cell death in the Drosophila ovary.
AB  - The Bcl-2 family has been shown to regulate mitochondrial dynamics during cell
      death in mammals and C. elegans, but evidence for this in Drosophila has been
      elusive. Here, we investigate the regulation of mitochondrial dynamics during
      germline cell death in the Drosophila melanogaster ovary. We find that
      mitochondria undergo a series of events during the progression of cell death,
      with remodeling, cluster formation and uptake of clusters by somatic follicle
      cells. These mitochondrial dynamics are dependent on caspases, the Bcl-2 family,
      the mitochondrial fission and fusion machinery, and the autophagy machinery.
      Furthermore, Bcl-2 family mutants show a striking defect in cell death in the
      ovary. These data indicate that a mitochondrial pathway is a major mechanism for
      activation of cell death in Drosophila oogenesis.

PMID- 21177346
TI  - Ripply3, a Tbx1 repressor, is required for development of the pharyngeal
      apparatus and its derivatives in mice.
AB  - The pharyngeal apparatus is a transient structure that gives rise to the thymus
      and the parathyroid glands and also contributes to the development of arteries
      and the cardiac outflow tract. A typical developmental disorder of the pharyngeal
      apparatus is the 22q11 deletion syndrome (22q11DS), for which Tbx1 is
      responsible. Here, we show that Ripply3 can modulate Tbx1 activity and plays a
      role in the development of the pharyngeal apparatus. Ripply3 expression is
      observed in the pharyngeal ectoderm and endoderm and overlaps with strong
      expression of Tbx1 in the caudal pharyngeal endoderm. Ripply3 suppresses
      transcriptional activation by Tbx1 in luciferase assays in vitro. Ripply3
      deficient mice exhibit abnormal development of pharyngeal derivatives, including
      ectopic formation of the thymus and the parathyroid gland, as well as
      cardiovascular malformation. Corresponding with these defects, Ripply3-deficient
      embryos show hypotrophy of the caudal pharyngeal apparatus. Ripply3 represses
      Tbx1-induced expression of Pax9 in luciferase assays in vitro, and Ripply3
      deficient embryos exhibit upregulated Pax9 expression. Together, our results show
      that Ripply3 plays a role in pharyngeal development, probably by regulating Tbx1
      activity.

PMID- 21177347
TI  - The Drosophila Nol12 homologue viriato is a dMyc target that regulates nucleolar
      architecture and is required for dMyc-stimulated cell growth.
AB  - The nucleolus is a subnuclear factory, the activity of which is required beyond
      ribosome biogenesis for the regulation of cell growth, death and proliferation.
      In both Drosophila and mammalian cells, the activity of the nucleolus is
      regulated by the proto-oncogene Myc. Myc induces the transcription of genes
      required for ribosome biogenesis and the synthesis of rRNA by RNA polymerase I, a
      nucleolar event that is rate limiting for cell growth. Here, we show that the
      fruit fly Nol12 homologue Viriato is a key determinant of nucleolar architecture
      that is required for tissue growth and cell survival during Drosophila
      development. We further show that viriato expression is controlled by Drosophila
      Myc (dMyc), and that the ability of dMyc to stimulate nucleolar and cellular
      growth depends on viriato expression. Therefore, viriato acts downstream of dMyc
      to ensure a coordinated nucleolar response to dMyc-induced growth and, thereby,
      normal organ development.

PMID- 21177350
TI  - Induction of labour for intrauterine growth restriction at term.

PMID- 21177348
TI  - Calcium/calmodulin-dependent protein kinase II activity regulates the
      proliferative potential of growth plate chondrocytes.
AB  - For tissues that develop throughout embryogenesis and into postnatal life, the
      generation of differentiated cells to promote tissue growth is at odds with the
      requirement to maintain the stem cell/progenitor cell population to preserve
      future growth potential. In the growth plate cartilage, this balance is achieved
      in part by establishing a proliferative phase that amplifies the number of
      progenitor cells prior to terminal differentiation into hypertrophic
      chondrocytes. Here, we show that endogenous calcium/calmodulin-dependent protein
      kinase II (CamkII, also known as Camk2) activity is upregulated prior to
      hypertrophy and that loss of CamkII function substantially blocks the transition
      from proliferation to hypertrophy. Wnt signaling and Pthrp-induced phosphatase
      activity negatively regulate CamkII activity. Release of this repression results
      in activation of multiple effector pathways, including Runx2- and beta-catenin
      dependent pathways. We present an integrated model for the regulation of
      proliferation potential by CamkII activity that has important implications for
      studies of growth control and adult progenitor/stem cell populations.

PMID- 21177349
TI  - Connective tissue fibroblasts and Tcf4 regulate myogenesis.
AB  - Muscle and its connective tissue are intimately linked in the embryo and in the
      adult, suggesting that interactions between these tissues are crucial for their
      development. However, the study of muscle connective tissue has been hindered by
      the lack of molecular markers and genetic reagents to label connective tissue
      fibroblasts. Here, we show that the transcription factor Tcf4 (transcription
      factor 7-like 2; Tcf7l2) is strongly expressed in connective tissue fibroblasts
      and that Tcf4(GFPCre) mice allow genetic manipulation of these fibroblasts. Using
      this new reagent, we find that connective tissue fibroblasts critically regulate
      two aspects of myogenesis: muscle fiber type development and maturation.
      Fibroblasts promote (via Tcf4-dependent signals) slow myogenesis by stimulating
      the expression of slow myosin heavy chain. Also, fibroblasts promote the switch
      from fetal to adult muscle by repressing (via Tcf4-dependent signals) the
      expression of developmental embryonic myosin and promoting (via a Tcf4
      independent mechanism) the formation of large multinucleate myofibers. In
      addition, our analysis of Tcf4 function unexpectedly reveals a novel mechanism of
      intrinsic regulation of muscle fiber type development. Unlike other intrinsic
      regulators of fiber type, low levels of Tcf4 in myogenic cells promote both slow
      and fast myogenesis, thereby promoting overall maturation of muscle fiber type.
      Thus, we have identified novel extrinsic and intrinsic mechanisms regulating
      myogenesis. Most significantly, our data demonstrate for the first time that
      connective tissue is important not only for adult muscle structure and function,
      but is a vital component of the niche within which muscle progenitors reside and
      is a critical regulator of myogenesis.

PMID- 21177351
TI  - Recent advances in the management of rheumatoid arthritis.

PMID- 21177353
TI  - 2010: a nudge in the wrong direction.

PMID- 21177354
TI  - Free healthcare in Sierra Leone.

PMID- 21177355
TI  - Cambodia's AIDS strategy could fail without sustainable financing.

PMID- 21177352
TI  - Induction versus expectant monitoring for intrauterine growth restriction at
      term: randomised equivalence trial (DIGITAT).
AB  - OBJECTIVE: To compare the effect of induction of labour with a policy of
      expectant monitoring for intrauterine growth restriction near term. DESIGN:
      Multicentre randomised equivalence trial (the Disproportionate Intrauterine
      Growth Intervention Trial At Term (DIGITAT)). SETTING: Eight academic and 44 non
      academic hospitals in the Netherlands between November 2004 and November 2008.
      PARTICIPANTS: Pregnant women who had a singleton pregnancy beyond 36+0 weeks'
      gestation with suspected intrauterine growth restriction. INTERVENTIONS:
      Induction of labour or expectant monitoring. MAIN OUTCOME MEASURES: The primary
      outcome was a composite measure of adverse neonatal outcome, defined as death
      before hospital discharge, five minute Apgar score of less than 7, umbilical
      artery pH of less than 7.05, or admission to the intensive care unit. Operative
      delivery (vaginal instrumental delivery or caesarean section) was a secondary
      outcome. Analysis was by intention to treat, with confidence intervals calculated
      for the differences in percentages or means. RESULTS: 321 pregnant women were
      randomly allocated to induction and 329 to expectant monitoring. Induction group
      infants were delivered 10 days earlier (mean difference -9.9 days, 95% CI -11.3
      to -8.6) and weighed 130 g less (mean difference -130 g, 95% CI -188 g to -71 g)
      than babies in the expectant monitoring group. A total of 17 (5.3%) infants in
      the induction group experienced the composite adverse neonatal outcome, compared
      with 20 (6.1%) in the expectant monitoring group (difference -0.8%, 95% CI -4.3%
      to 3.2%). Caesarean sections were performed on 45 (14.0%) mothers in the
      induction group and 45 (13.7%) in the expectant monitoring group (difference
      0.3%, 95% CI -5.0% to 5.6%). CONCLUSIONS: In women with suspected intrauterine
      growth restriction at term, we found no important differences in adverse outcomes
      between induction of labour and expectant monitoring. Patients who are keen on
      non-intervention can safely choose expectant management with intensive maternal
      and fetal monitoring; however, it is rational to choose induction to prevent
      possible neonatal morbidity and stillbirth. TRIAL REGISTRATION: International
      Standard Randomised Controlled Trial number ISRCTN10363217.

PMID- 21177358
TI  - If the pope can change his mind on condoms, why not emergency contraceptives?

PMID- 21177361
TI  - US drug companies paid $15bn in fines for fraudulent marketing in past five
      years.

PMID- 21177364
TI  - 2, 4-dinitrophenol poisoning caused by non-oral exposure.
AB  - 2, 4-Dinitrophenol (2, 4-DNP) is widely used in industry, but recently, poisoning
      through consumption for weight control has been frequently reported. We report
      the cases of two patients whose deaths were attributed to occupational and non
      oral exposure of 2, 4-DNP. They were all poisoned through skin absorption and
      respiratory tract inhalation; common features were excessive sweating,
      hyperthermia, tachycardia, clouded consciousness and asystole. Because of the
      lack of specific early symptoms, effective antidotes and the means of washing the
      contamination from the skin, their arrival in hospital was delayed and the
      supportive therapy was ineffectual. Cardiac arrest occurred quickly and
      unexpected after admission.

PMID- 21177365
TI  - The emerging roles of microRNAs in the molecular responses of metabolic rate
      depression.
AB  - Metabolic rate depression is an important survival strategy for many animal
      species and a common element of hibernation, torpor, estivation, anoxia and
      diapause. Studies of the molecular mechanisms that regulate reversible
      transitions to and from hypometabolic states have identified principles of
      regulatory control. These control mechanisms are conserved among biologically
      diverse organisms and include the coordinated reduction of specific groups of key
      regulatory enzymes or proteins in the cell, a process likely driven by microRNA
      target repression/degradation. The present review focuses on a growing area of
      research in hypometabolism and mechanisms involving the rapid and reversible
      control of translation facilitated by microRNAs. The analysis draws primarily
      from current research on three animal models: hibernating mammals, anoxic turtles
      and freeze-tolerant frogs (with selected examples from multiple other sources).
      Here, we demonstrate a link between metabolic rate depression, a well-documented
      response to periods of environmental stress, and microRNA expression. Microarray
      based expression profiles and PCR-driven studies have revealed that specific
      microRNAs are induced in response to environmental stress. Selected members of
      this group decrease pro-apoptotic signaling, reduce muscle wasting and reduce
      protein translation, whereas other members contribute to cell cycle arrest and
      mitogen-activated protein kinase signaling. Many of the same microRNAs are
      frequently deregulated in numerous disease pathologies and, hence, the
      hypometabolism model could provide a novel approach for the treatment of stroke
      and heart attack in humans.

PMID- 21177366
TI  - Do smokers of menthol cigarettes find it harder to quit smoking?
AB  - INTRODUCTION: Menthol cigarette smokers may find it harder to quit smoking than
      smokers of nonmenthol cigarettes. METHODS: We conducted a systematic review of
      published studies examining the association between menthol cigarette smoking and
      cessation. Electronic databases and reference lists were searched to identify
      studies published through May 2010, and results were tabulated. RESULTS: Ten
      studies were located that reported cessation outcomes for menthol and nonmenthol
      smokers. Half of the studies found evidence that menthol smoking is associated
      with lower odds of cessation, while the other half found no such effects. The
      pattern of results in these studies suggest that the association between smoking
      menthol cigarettes and difficulty quitting is stronger in (a) racial/ethnic
      minority populations, (b) younger smokers, and (c) studies carried out after
      1999. This pattern is consistent with an effect that relies on menthol to
      facilitate increased nicotine intake from fewer cigarettes where economic
      pressure restricts the number of cigarettes smokers can afford to purchase.
      CONCLUSIONS: There is growing evidence that certain subgroups of smokers find it
      harder to quit menthol versus nonmenthol cigarettes. There is a need for
      additional research, and particularly for studies including adequately powered
      and diverse samples of menthol and nonmenthol smokers, with reliable measurement
      of cigarette brands, socioeconomic status, and biomarkers of nicotine intake.

PMID- 21177367
TI  - The role of menthol in cigarettes as a reinforcer of smoking behavior.
AB  - INTRODUCTION: The World Health Organization has identified several additives such
      as menthol in the manufacturing of cigarettes to specifically reduce smoke
      harshness. These additives may have important implications for reinforcing
      smoking behavior and motivation to quit smoking. The purpose of this paper is to
      synthesize research related to the role of menthol's sensory characteristics in
      strengthening the reinforcing effects of nicotine in cigarettes and the impact on
      nicotine addiction and smoking behavior. METHODS: Research reports from 2002 to
      2010 on the addictive potential of menthol cigarettes were reviewed that included
      qualitative focus groups, self-reports and biomarkers of nicotine dependence,
      human laboratory, and epidemiological studies. RESULTS: Positive sensory effects
      of menthol cigarette use were identified via reports of early smoking experiences
      and as a potential starter product for smoking uptake in youth. Menthol
      cigarettes may serve as a conditioned stimulus that reinforces the rewarding
      effects of smoking. Nicotine dependence measured by shorter time-to-first
      cigarette upon waking was increased with menthol cigarette use in most of the
      studies reviewed. Smoking quit rates provide additional indicators of nicotine
      dependence, and the majority of the studies reviewed provided evidence of lower
      quit rates or higher relapse rates among menthol cigarette smokers. CONCLUSIONS:
      The effects of menthol cigarette use in increasing the reinforcing effects of
      nicotine on smoking behavior were evidenced in both qualitative and quantitative
      empirical studies. These findings have implications for enhanced prevention and
      cessation efforts in menthol smokers.

PMID- 21177368
TI  - Menthol cigarette use among racial and ethnic groups in the United States, 2004
      2008.
AB  - INTRODUCTION: Understanding the patterns of menthol cigarette use can be useful
      in developing and justifying policies designed to prevent and reduce cigarette
      use and exposure to tobacco smoke. This report provides an update and summary of
      the demographic distribution and trends of menthol cigarette use in the United
      States. METHODS: Data from the 2004-2008 National Survey on Drug Use and Health
      were analyzed to estimate menthol cigarette use among current smokers by
      race/ethnicity, sex, and age (12 years and older). A t-test was used to compare
      estimates for menthol and nonmenthol use by demographic group. Trend analyses
      were conducted to examine differences in menthol cigarette use by race/ethnicity
      and age from 2004 to 2008. RESULTS: Over half of menthol cigarette smokers were
      female (52.2%), and approximately 29.4% of all menthol smokers were Black, which
      was almost 10 times the percentage of nonmenthol smokers who were Black (3.0%, p
      < .01). Prevalence of past month menthol cigarette use was highest among current
      smokers aged 12-17 years (44.7%) and decreased as age group increased. From 2004
      to 2008, menthol cigarette use increased significantly among White smokers aged
      12-17 years (from 40.3% in 2004 to 46.0% in 2008, p < .01). Menthol cigarette use
      among young adult smokers aged 18-25 years increased for Hispanics (from 33.9% in
      2004 to 42.4% in 2008, p < .01) and Whites (from 26.7% to 32.5%, p < .01).
      CONCLUSIONS: Demographic disparities in menthol cigarette use persist in the
      United States. Continued monitoring and improvement of existing surveillance
      systems to identify patterns and trends in menthol cigarette use are needed.

PMID- 21177369
TI  - Perceptions of menthol cigarette use among U.S. adults and adult smokers:
      findings from the 2009 HealthStyles survey.
AB  - INTRODUCTION: Perceptions of menthol cigarette use may have implications for
      smoking initiation and cessation. This study explores harm and health perceptions
      of menthol cigarette use among a national sample of U.S. adults and current
      smokers. METHODS: We examined data from the 2009 HealthStyles survey (n = 4,556),
      an annual mail survey of adults >=18 years of age that collects information on
      attitudes and behaviors, including smoking. Frequencies and weighted percentages
      were calculated by sex, race/ethnicity, age, education level, household income,
      and smoking status. Unadjusted odds ratios (OR) were used to compare perceptions
      of menthol cigarette use between demographic groups. RESULTS: Close to half of
      adults (45.8%) believed that menthol cigarettes are just as harmful as nonmenthol
      cigarettes, and 40.9% of adults did not know whether menthol cigarettes are more
      or less harmful than nonmenthol cigarettes. Few adults (0.6%), including smokers,
      perceived menthol cigarettes to be less harmful than nonmenthol cigarettes.
      Blacks (OR = 3.22, 95% CI = 1.80-5.76) were more likely to believe that menthol
      cigarettes have health benefits when compared with Whites. Almost half of current
      smokers believed menthol cigarettes are equally addictive as nonmenthol
      cigarettes and 74.9% believed menthol and nonmenthol cigarettes are equally hard
      to quit. CONCLUSIONS: Findings suggest directions for targeted public health
      messages for menthol cigarette use. Future research is needed among a nationally
      representative sample to capture more subtle differences in perceptions among
      menthol and nonmenthol smokers.

PMID- 21177370
TI  - Menthol cigarettes contribute to the appeal and addiction potential of smoking
      for youth.
AB  - INTRODUCTION: Menthol cigarettes are a common choice of cigarettes among young
      smokers that contribute to the addictive potential of cigarette smoking. METHODS:
      We reviewed prior research and analyzed the 2006 National Youth Tobacco Survey
      (NYTS), using logistic regression to assess the relationship between menthol
      cigarette use and needing a cigarette within 1 hr after smoking. RESULTS: In the
      2006 NYTS, 51.7% (95% CI: 45.8-57.5) of middle school smokers and 43.1% (95%
      C.I.: 37.0, 49.1) of high school smokers reported that they usually smoked a
      menthol brand of cigarettes, using a menthol smoking status definition based on
      consistency between smokers' report of the brand and the menthol status of the
      cigarettes they usually smoked. A logistic regression model of dependence,
      controlling for background (i.e., school level, gender, and race/ethnicity) and
      smoking level (i.e., years, frequency, and level of smoking) found that smoking
      menthol cigarettes was significantly associated with reduced time to needing a
      cigarette among smokers with a regular brand (odds ratio [OR]: 1.86, p = .003)
      and among established smokers (OR: 2.06, p = .001). This is consistent with other
      studies that found that youth who smoked menthol cigarettes were significantly
      more likely than those who smoked nonmenthol cigarettes to report signs of
      nicotine dependency. CONCLUSIONS: Menthol cigarettes contribute to the appeal of
      youth smoking and to the addictive potential of smoking cigarettes among youth.
      It is important to control the use of menthol cigarettes and to implement
      cessation strategies that are effective with youth smokers.

PMID- 21177371
TI  - The menthol marketing mix: targeted promotions for focus communities in the
      United States.
AB  - INTRODUCTION: This study analyzes tobacco industry menthol marketing strategies
      aimed at urban predominantly Black populations. METHODS: Data are drawn from an
      interview with a former Brown & Williamson Tobacco Company trade marketing
      manager, tobacco industry documents on Kool promotions in urban areas, and public
      health literature on tobacco marketing. RESULTS: Tobacco companies recognize the
      growth potential for the menthol segment in these urban communities. They have
      higher levels of price discounts and signage, exert tight controls over the
      retail environment, and use hip-hop lifestyle to associate menthol products with
      urban nightlife, music, fame, and cultural edginess among younger smokers.
      CONCLUSIONS: Tobacco companies regard the urban Black menthol segment as one of
      the few markets in which they can grow sales despite declines elsewhere in the
      United States. Consequently, this population is surrounded by intense and
      integrated levels of marketing. We need strong monitoring, regulation, and
      enforcement efforts that will counter the industry's use of menthol at multiple
      levels in urban environments.

PMID- 21177372
TI  - Menthol cigarettes: moving toward a broader definition of harm.
AB  - RATIONALE: The current practice of the tobacco industry of primarily focusing on
      the extent that menthol cigarettes contribute or do not contribute to excess
      morbidity and mortality in various diseases does not, in and of itself, fully
      illuminate the harm caused by these products. In fact, this practice actually
      masks and obscures the public health harm associated with menthol cigarettes.
      Given this, this commentary develops and presents a broader definition of harm in
      which to view menthol cigarettes and as the necessary and underlying rationale of
      why this candy-flavored ingredient should be removed from all tobacco products.
      METHODS: This paper relies on the scientific presentations of the 2nd Conference
      on Menthol Cigarettes, and the peer-reviewed literature on menthol cigarettes.
      OUTCOMES: A broader definition of harm from menthol cigarettes must be analyzed
      from a broad public health perspective and take into account youth uptake and
      initiation, menthol's ability to augment addiction through unique sensory
      properties, spurious health messages associated with these products, menthol's
      role in cessation inhibition and relapse promotion, and the blatant predatory
      marketing of these products to the most vulnerable sectors of society.
      CONCLUSIONS: The Food and Drug Administration (FDA) should apply the same logic
      that outlawed other candy flavorings and apply it to menthol cigarettes; in the
      end, all candy flavorings, including menthol, only serve to make the poisons
      inherent in tobacco smoke go down easier. Additionally, the mobilization of
      communities most affected by the menthol cigarettes, the FDA, and candy
      flavorings and the tobacco industry's machinations will be discussed.

PMID- 21177373
TI  - Why we should make menthol cigarettes history.

PMID- 21177374
TI  - Tobacco industry knowledge of the role of menthol in chemosensory perception of
      tobacco smoke.
AB  - Sensory perception is a key determinant of smoking behavior and, therefore,
      reinforcement and addiction. The tobacco industry has conducted extensive
      research on the chemosensory and physiological effects of menthol in tobacco
      smoke and has actively promoted menthol's sensory characteristics. Based upon
      previously published examinations of internal tobacco industry documents, this
      commentary summarizes what is currently known about the tobacco industry's use of
      menthol to modify sensory characteristics in cigarettes and the implications of
      these activities for smoking behavior. The industry considers menthol to be an
      important tool for modulating the sensory effects of nicotine in different
      product variations, particularly those designed to be acceptable to "starters" or
      people interested in quitting. Regulatory efforts should consider that menthol
      enables the tobacco industry to customize a highly addictive product in a manner
      that contributes to initiation and deters cessation due to its chemosensory
      effects.

PMID- 21177375
TI  - ENMD-2076 is an orally active kinase inhibitor with antiangiogenic and
      antiproliferative mechanisms of action.
AB  - ENMD-2076 is a novel orally active, small molecule kinase inhibitor with a
      mechanism of action involving several pathways key to tumor growth and survival:
      angiogenesis, proliferation, and the cell cycle. ENMD-2076 has selective activity
      against the mitotic kinase Aurora A, as well as kinases involved in angiogenesis
      (VEGFRs, FGFRs). ENMD-2076 inhibited the growth in vitro of a wide range of human
      solid tumor and hematopoietic cancer cell lines with IC(50) values ranging from
      0.025 to 0.7 MUmol/L. ENMD-2076 was also shown to induce regression or complete
      inhibition of tumor growth in vivo at well-tolerated doses in tumor xenograft
      models derived from breast, colon, melanoma, leukemia, and multiple myeloma cell
      lines. Pharmacodynamic experiments in vivo showed that in addition to inhibiting
      Aurora A, single doses of ENMD-2076 had sustained inhibitory effects on the
      activation of Flt3 as well as the angiogenic tyrosine kinases, VEGFR2/KDR and
      FGFR1 and 2. ENMD-2076 was shown to prevent the formation of new blood vessels
      and regress formed vessels in vivo at doses equivalent to those that gave
      substantial activity in tumor xenograft models. These results indicate that ENMD
      2076 is a well-tolerated, orally active multitarget kinase inhibitor with a
      unique antiangiogenic/antiproliferative profile and provides strong preclinical
      support for use as a therapeutic for human cancers. Several phase 1 studies
      involving ENMD-2076 have been recently completed, and the compound is currently
      being evaluated in a phase 2 clinical trial in patients with platinum-resistant
      ovarian cancer.

PMID- 21177376
TI  - Ku can contribute to telomere lengthening in yeast at multiple positions in the
      telomerase RNP.
AB  - Unlike ribonucleoprotein complexes that have a highly ordered overall
      architecture, such as the ribosome, yeast telomerase appears to be much more
      loosely constrained. Here, we investigate the importance of positioning of the Ku
      subunit within the 1157-nt yeast telomerase RNA (TLC1). Deletion of the 48-nt Ku
      binding hairpin in TLC1 RNA (tlc1Delta48) reduces telomere length, survival of
      cells with gross chromosomal rearrangements, and de novo telomere addition at a
      broken chromosome end. To test the function of Ku at novel positions in the
      telomerase RNP, we reintroduced its binding site into tlc1Delta48 RNA at position
      446 or 1029. We found that Ku bound to these repositioned sites in vivo and
      telomere length increased slightly, but statistically significantly. The ability
      of telomerase to promote survival of cells with gross chromosomal rearrangements
      by healing damaged chromosome arms was also partially restored, whereas the
      kinetics of DNA addition to a specific chromosome break was delayed. Having two
      Ku sites in TLC1 caused progressive hyperelongation of a variable subset of
      telomeres, consistent with Ku's role in telomerase recruitment to chromosome
      ends. The number of Ku-binding sites in TLC1 contributed to telomerase RNA
      abundance in vivo but was only partially responsible for telomere length
      phenotypes. Thus, telomerase RNA levels and telomere length regulation can be
      modulated by the number of Ku sites in telomerase RNA. Furthermore, there is
      substantial flexibility in the relative positioning of Ku in the telomerase RNP
      for native telomere length maintenance, although not as much flexibility as for
      the essential Est1p subunit.

PMID- 21177377
TI  - Early growth response gene 1 (Egr-1) is required for new and reactivated fear
      memories in the lateral amygdala.
AB  - The immediate-early gene early growth response gene-1 (EGR-1, zif-268) has been
      extensively studied in synaptic plasticity and memory formation in a variety of
      memory systems. However, a convincing role for EGR-1 in amygdala-dependent memory
      consolidation processes has yet to emerge. In the present study, we have examined
      the role of EGR-1 in the consolidation and reconsolidation of amygdala-dependent
      auditory Pavlovian fear conditioning. In our first series of experiments, we show
      that EGR-1 is regulated following auditory fear conditioning in the lateral
      nucleus of the amygdala (LA). Next, we use antisense oligodeoxynucleotide (ODN)
      knockdown of EGR-1 in the LA to show that training-induced expression of EGR-1 is
      required for memory consolidation of auditory fear conditioning; that is, long
      term memory (LTM) is significantly impaired while acquisition and short-term
      memory (STM) are intact. In a second set of experiments, we show that EGR-1 is
      regulated in the LA by retrieval of an auditory fear memory. We then show that
      retrieval-induced expression of EGR-1 in the LA is required for memory
      reconsolidation of auditory fear conditioning; that is, post-retrieval (PR)-LTM
      is significantly impaired while memory retrieval and PR-STM are intact.
      Additional experiments show these effects to be restricted to the LA, to be
      temporally graded, and unlikely to be due to nonspecific toxicity within the LA.
      Collectively, our findings strongly implicate a role for EGR-1 in both the
      initial consolidation and in the reconsolidation of auditory fear memories in the
      LA.

PMID- 21177379
TI  - Select heterozygous Keap1 mutations have a dominant-negative effect on wild-type
      Keap1 in vivo.
AB  - Under homeostatic conditions, Keap1 constitutively mediates the proteasomal
      degradation Nrf2. However, tertiary changes in Keap1 in response to the cellular
      environment allow for liberation of Nrf2 to transcriptionally regulate downstream
      cytoprotective genes that aid in cell survival. KEAP1/NRF2 somatic mutations
      causing constitutive NRF2 activation have been estimated to occur in
      approximately 25% of human lung tumors, with similar rates believed to exist in
      other tissue subtypes. As the stoichiometry between Keap1 and Nrf2 is 2:1, we
      hypothesized that heterozygous Keap1 mutations could suppress wild-type Keap1
      (Keap1(WT)) activity by functioning as a dominant-negative protein through
      heterodimerization of mutant Keap1 (Keap1(mutant)) with Keap1(WT). When
      Keap1(G430C) or Keap1(G364C) mutants were expressed in lieu of Keap1(WT),
      premature juvenile mortality was observed. To test the hypothesis of a dominant
      negative effect, Keap1-null mice were engineered to coexpress both Keap1(WT) and
      Keap1(G430C) transgenes, a phenotype analogous to that previously observed from a
      human lung tumor. These mice were viable, but phenotypically displayed
      hyperactivation of downstream Nrf2 target genes and moderate esophageal
      hyperkeratosis. Similar to the transgenic mouse Keap1(G430C) mutant,
      Keap1(C273&288A) substitutions also diminished Keap1(WT) activity in vivo. To
      further delineate involvement of the dominant-negative heterodimer, transgenic
      mice with a deletion or strategic mutation in Broad-complex, Tramtrack and Bric-a
      Brac (BTB) domain that disallowed Keap1 dimerization were generated in the
      presence of Keap1(WT), and failed to induce the dominant-negative effect in vivo.
      These results thus demonstrate that sequestration of Keap1(WT) into a
      Keap1(mutant)-Keap1(WT) heterodimer leads to a dominant-negative effect in vivo
      and gives rise to Nrf2 activation.

PMID- 21177378
TI  - A presynaptic role for FMRP during protein synthesis-dependent long-term
      plasticity in Aplysia.
AB  - Loss of the Fragile X mental retardation protein (FMRP) is associated with
      presumed postsynaptic deficits in mouse models of Fragile X syndrome. However,
      the possible presynaptic roles of FMRP in learning-related plasticity have
      received little attention. As a result, the mechanisms whereby FMRP influences
      synaptic function remain poorly understood. To investigate the cellular locus of
      the effects of FMRP on synaptic plasticity, we cloned the Aplysia homolog of FMRP
      and find it to be highly expressed in neurons. By selectively down-regulating
      FMRP in individual Aplysia neurons at the sensory-to-motor neuron synapse
      reconstituted in co-cultures, we demonstrate that FMRP functions both pre- and
      postsynaptically to constrain the expression of long-term synaptic depression
      induced by repeated pulses of FMRF-amide. In contrast, FMRP has little to no
      effect on long-term synaptic facilitation induced by repeated pulses of
      serotonin. Since other components of signaling pathways involved in plasticity
      appear to be conserved between Aplysia and mammalian neurons, our findings
      suggest that FMRP can participate in both pre- and postsynaptic regulation of
      enduring synaptic plasticity that underlies the storage of certain types of long
      term memory.

PMID- 21177380
TI  - Therapeutic antibody targeting of CD47 eliminates human acute lymphoblastic
      leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and
      constitutes 15% of adult leukemias. Although overall prognosis for pediatric ALL
      is favorable, high-risk pediatric patients and most adult patients have
      significantly worse outcomes. Multiagent chemotherapy is standard of care for
      both pediatric and adult ALL, but is associated with systemic toxicity and long
      term side effects and is relatively ineffective against certain ALL subtypes.
      Recent efforts have focused on the development of targeted therapies for ALL
      including monoclonal antibodies. Here, we report the identification of CD47, a
      protein that inhibits phagocytosis, as an antibody target in standard and high
      risk ALL. CD47 was found to be more highly expressed on a subset of human ALL
      patient samples compared with normal cell counterparts and to be an independent
      predictor of survival and disease refractoriness in several ALL patient cohorts.
      In addition, a blocking monoclonal antibody against CD47 enabled phagocytosis of
      ALL cells by macrophages in vitro and inhibited tumor engraftment in vivo.
      Significantly, anti-CD47 antibody eliminated ALL in the peripheral blood, bone
      marrow, spleen, and liver of mice engrafted with primary human ALL. These data
      provide preclinical support for the development of an anti-CD47 antibody therapy
      for treatment of human ALL.

PMID- 21177382
TI  - Normalization strategy is critical for the outcome of miRNA expression analyses
      in the rat heart.
AB  - Since normalization strategies plays a pivotal role for obtaining reliable
      results when performing quantitative PCR (qPCR) analyses, this study investigated
      several miRNA normalization candidates in regards to their efficiency as
      normalization standards in the ischemic reperfused ex vivo rat heart, with
      special reference to regulation of the miRNAs miR-1 and miR-101b. The possibility
      of including primers for several miRNAs in one reverse transcription (RT)
      reaction was also investigated. Langendorff perfused rat hearts were subjected to
      30 min regional ischemia and 0, 1, 5, 15, or 120 min reperfusion. Total RNA was
      isolated and reverse transcribed for miRNA qPCR analysis. Normalization
      candidates were evaluated by the NormFinder and geNorm algorithms and the
      following stability expression rank order was obtained: sno202 < U6B < U87 <
      snoRNA < 4.5S RNA A < Y1 < 4.5S RNA B < GAPDH. Applying U6B as a normalizer it
      was found that miR-1 and miR-101b was downregulated in the ischemic reperfused
      myocardium. Furthermore, up to three primers could be included in one RT reaction
      by replacing RNase-free water with two supplemental sets of primers in the TaqMan
      MicroRNA assay protocol. This study demonstrates the importance of validating
      normalization standards when performing miRNA expression analyses by qPCR, and
      that miR-1 and miR-101b may play an important role during early reperfusion of
      the ischemic rat heart.

PMID- 21177381
TI  - Genetic analysis of mouse strains with variable serum sodium concentrations
      identifies the Nalcn sodium channel as a novel player in osmoregulation.
AB  - In central osmoregulation, a 1-2% rise in plasma osmolality is detected by
      specialized osmoreceptors located in the circumventricular organs of the
      hypothalamus. A disturbance in this tightly regulated balance will result in
      either hyponatremia or hypernatremia, which are both common electrolyte disorders
      in hospitalized patients. Despite the high clinical importance of hypo- and
      hypernatremia and the fact that this vital process has been studied for many
      years, the genes and corresponding proteins involved in this process are just
      beginning to be identified. To identify novel genes involved in the (patho
      )physiology of osmoregulation, we therefore employed haplotype association
      mapping on an aging group of 27 inbred mouse strains. Serum sodium concentrations
      were determined in all strains at 6, 12, and 18 mo of age, and high-resolution
      mapping was performed for males and females separately. We identified a total of
      five loci associated with the serum sodium concentration of which the locus on
      chromosome 14, containing only one known gene (Nalcn), showed the strongest
      correlation. Within this locus three different haplotypes could be distinguished,
      which associated with different average serum sodium levels. The association of
      Nalcn with sodium levels was confirmed by analysis of heterozygous Nalcn knockout
      mice, which displayed hypernatremia compared with wild-type littermates. Our
      study demonstrates that Nalcn associates with serum sodium concentrations in mice
      and indicates that Nalcn is an important novel player in osmoregulation.

PMID- 21177383
TI  - Selective gene expression by rat gastric corpus epithelium.
AB  - The gastrointestinal (GI) tract is divided into several segments that have
      distinct functional properties, largely absorptive. The gastric corpus is the
      only segment thought of as largely secretory. Microarray hybridization of the
      gastric corpus mucosal epithelial cells was used to compare gene expression with
      other segments of the columnar GI tract followed by statistical data subtraction
      to identify genes selectively expressed by the rat gastric corpus mucosa. This
      provides a means of identifying less obvious specific functions of the corpus in
      addition to its secretion-related genes. For example, important properties found
      by this GI tract comparative transcriptome reflect the energy demand of acid
      secretion, a role in lipid metabolism, the large variety of resident
      neuroendocrine cells, responses to damaging agents and transcription factors
      defining differentiation of its epithelium. In terms of overlap of gastric corpus
      genes with the rest of the GI tract, the distal small bowel appears to express
      many of the gastric corpus genes in contrast to proximal small and large bowel.
      This differential map of gene expression by the gastric corpus epithelium will
      allow a more detailed description of major properties of the gastric corpus and
      may lead to the discovery of gastric corpus cell differentiation genes and those
      mis-regulated in gastric carcinomas.

PMID- 21177385
TI  - The importance of being Earnest: I can't glean which gene you mean.

PMID- 21177384
TI  - Mitochondrial and plasma membrane lactate transporter and lactate dehydrogenase
      isoform expression in breast cancer cell lines.
AB  - We hypothesized that dysregulation of lactate/pyruvate (monocarboxylate)
      transporters (MCT) and lactate dehydrogenase (LDH) isoforms contribute to the
      Warburg effect in cancer. Therefore, we assayed for the expression levels and the
      localizations of MCT (1, 2, and 4), and LDH (A and B) isoforms in breast cancer
      cell lines MCF-7 and MDA-MB-231 and compared results with those from a control,
      untransformed primary breast cell line, HMEC 184. Remarkably, MCT1 is not
      expressed in MDA-MB-231, but MCT1 is expressed in MCF-7 cells, where its
      abundance is less than in control HMEC 184 cells. When present in HMEC 184 and
      MCF-7 cells, MCT1 is localized to the plasma membrane. MCT2 and MCT4 were
      expressed in all the cell lines studied. MCT4 expression was higher in MDA-MB-231
      compared with MCF-7 and HMEC 184 cells, whereas MCT2 abundance was higher in MCF
      7 compared with MDA-MB-231 and HMEC 184 cells. Unlike MCT1, MCT2 and MCT4 were
      localized in mitochondria in addition to the plasma membrane. LDHA and LDHB were
      expressed in all the cell-lines, but abundances were higher in the two cancer
      cell lines than in the control cells. MCF-7 cells expressed mainly LDHB, while
      MDA-MB-231 and control cells expressed mainly LDHA. LDH isoforms were localized
      in mitochondria in addition to the cytosol. These localization patterns were the
      same in cancerous and control cell lines. In conclusion, MCT and LDH isoforms
      have distinct expression patterns in two breast cancer cell lines. These
      differences may contribute to divergent lactate dynamics and oxidative capacities
      in these cells, and offer possibilities for targeting cancer cells.

PMID- 21177386
TI  - Signal-to-noise ratio improvement in dynamic contrast-enhanced CT and MR imaging
      with automated principal component analysis filtering.
AB  - PURPOSE: To develop a new automated filtering technique and to evaluate its
      ability to compensate for the known low contrast-to-noise ratio (CNR) in dynamic
      contrast material-enhanced (DCE) magnetic resonance (MR) and computed tomographic
      (CT) data, without substantial loss of information. MATERIALS AND METHODS:
      Clinical data acquisition for this study was approved by the institutional review
      board. Principal component analysis (PCA) was combined with the fraction of
      residual information (FRI) criterion to optimize the balance between noise
      reduction efficiency and information conservation. The PCA FRI filter was
      evaluated in 15 DCE MR imaging data sets and 15 DCE CT data sets by two
      radiologists who performed visual analysis and quantitative assessment of noise
      reduction after filtering. RESULTS: Visual evaluation revealed a substantial
      noise reduction while conserving information in 90% of MR imaging cases and 87%
      of CT cases for image analysis and in 93% of MR imaging cases and 90% of CT cases
      for signal analysis. Efficient denoising enabled improvement in structure
      characterization in 60% of MR imaging cases and 77% of CT cases. After filtering,
      CNR was improved by 2.06 +/- 0.89 for MR imaging (P < .01) and by 5.72 +/- 4.82
      for CT (P < .01). CONCLUSION: This PCA FRI filter demonstrates noise reduction
      efficiency and information conservation for both DCE MR data and DCE CT data. FRI
      analysis enabled automated optimization of the parameters for the PCA filter and
      provided an optional visual control of residual information losses. The robust
      and fast PCA FRI filter may improve qualitative or quantitative analysis of DCE
      imaging in a clinical context. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100231/-/DC1.

PMID- 21177387
TI  - Evolution of femoral condylar ossification at MR imaging: frequency and patient
      age distribution.
AB  - PURPOSE: To determine how the magnetic resonance (MR) signal intensity seen with
      variability in distal femoral epiphyseal ossification in children varies with (a)
      age, (b) sex, (c) distribution to the medial or lateral condyles, and (d)
      residual physeal cartilage. MATERIALS AND METHODS: Ethics committee approval was
      obtained, and informed patient consent was waived. Two pediatric radiologists
      retrospectively reviewed the consecutive knee MR imaging studies of 910 children
      (457 boys, 453 girls; age range, 0.7-16.9 years) for variability in ossification
      and categorized the variability as preossification center, early ossification
      center, puzzle piece, incomplete puzzle piece, spiculation, or accessory
      ossification center. Patient age and sex, ossification variability site, residual
      physeal cartilage, and associated findings were analyzed. Basic descriptive
      statistical analysis, Student t tests for comparison of continuous variables, and
      kappa statistics analysis of interobserver agreement were performed where
      appropriate. RESULTS: In 202 (22.2%) patients (278 condyles), ossification
      variability was present. In the 910 patients, early ossification center (n = 172,
      18.9%) and spiculated configuration of the secondary ossification center (n =
      151, 16.6%) were the most common variants. Preossification center (50 [5.5%]
      patients), puzzle piece (26 [2.9%] patients), accessory ossification center (nine
      [1.0%] patients), and incomplete puzzle piece (two [0.2%] patients) were seen
      less often. Ossification variability was more common in the medial condyles (169
      [18.6%] of 910 cases) than in the lateral condyles (109 [12.0%] of 910 cases),
      nearly always posteriorly located (277 [99.6%] of 278 condyles), and more common
      in boys (153/457 [33.5%]) than in girls (49/453 [10.8%]). Ossification
      variability was less common with decreasing residual physeal cartilage. Peak
      patient age ranges for ossification variability were 2-12 years for boys and 2-10
      years for girls. CONCLUSION: Ossification variability in the femoral condyles is
      common in children and should not be confused with abnormal processes.

PMID- 21177388
TI  - The mammographic density of a mass is a significant predictor of breast cancer.
AB  - PURPOSE: To determine whether the mammographic density of noncalcified solid
      breast masses is associated with malignancy and to measure the agreement between
      prospective and retrospective assessment. MATERIALS AND METHODS: The
      institutional review board approved this study and waived informed consent. Three
      hundred forty-eight consecutive breast masses in 328 women who underwent image
      guided or surgical biopsy between October 2005 and December 2007 were included.
      All 348 biopsy-proved masses were randomized and assigned to a radiologist who
      was blinded to biopsy results for retrospective assessment by using the Breast
      Imaging Reporting and Data System (retrospectively assessed data set). Clinical
      radiologists prospectively assessed the density of 180 of these masses
      (prospectively assessed data set). Pathologic result at biopsy was the reference
      standard. Benign masses were followed for at least 1 year by linking each patient
      to a cancer registry. Univariate analyses were performed on the retrospectively
      assessed data set. The association of mass density and malignancy was examined by
      creating a logistic model for the prospectively assessed data set. Agreement
      between prospective and retrospective assessments was calculated by using the
      kappa statistic. RESULTS: In the retrospectively assessed data set, 70.2% of high
      density masses were malignant, and 22.3% of the isodense or low-density masses
      were malignant (P < .0001). In the prospective logistic model, high density (odds
      ratio, 6.6), irregular shape (odds ratio, 9.9), spiculated margin (odds ratio,
      20.3), and age (beta = 0.09, P < .0001) were significantly associated with the
      probability of malignancy. The kappa value for prospective-retrospective
      agreement of mass density was 0.53. CONCLUSION: High mass density is
      significantly associated with malignancy in both retrospectively and
      prospectively assessed data sets, with moderate prospective-retrospective
      agreement. Radiologists should consider mass density as a valuable descriptor
      that can stratify risk. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100328/-/DC1.

PMID- 21177389
TI  - Bimodal thrombus imaging: simultaneous PET/MR imaging with a fibrin-targeted dual
      PET/MR probe--feasibility study in rat model.
AB  - PURPOSE: To image thrombus by using magnetic resonance (MR) imaging and positron
      emission tomography (PET) simultaneously in a rat arterial thrombus model with a
      dual PET/MR probe. MATERIALS AND METHODS: Animal studies were approved by the
      institutional animal use committee. A dual PET/MR probe was synthesized by means
      of partial exchange of gadolinium for copper 64 ((64)Cu) in the fibrin-targeted
      MR probe EP-2104R. A preformed 25-mm thrombus was injected into the right
      internal carotid artery of a rat. Imaging was performed with a clinical 3.0-T MR
      imager with an MR-compatible human PET imager. Rats (n = 5) were imaged prior to
      and after systemic administration of the dual probe by using simultaneous PET/MR.
      The organ distribution of (64)Cu and gadolinium was determined ex vivo (n = 8), 2
      hours after injection by using well counting and inductively coupled plasma mass
      spectrometry, respectively. Signal intensity ratios (SIRs) between the thrombus
      containing and contralateral vessel were computed from PET images and MR data
      before and after probe administration. RESULTS: The dual probe was synthesized
      with greater than 98% radiochemical purity. Thrombus enhancement was observed in
      all five animals at both MR (SIR([postprobe])/SIR([preprobe]) = 1.71 +/- 0.35, P
      = .0053) and PET (SIR = 1.85 +/- 0.48, P = .0087) after injection of the dual
      PET/MR probe. Ex vivo analysis at 2 hours after injection showed the highest
      (64)Cu and gadolinium concentrations, after the excretory organs (kidney and
      liver), to be in the thrombus. CONCLUSION: A fibrin-targeted dual PET/MR probe
      enables simultaneous, direct MR and PET imaging of thrombus.

PMID- 21177390
TI  - Is apparent diffusion coefficient associated with clinical risk scores for
      prostate cancers that are visible on 3-T MR images?
AB  - PURPOSE: To investigate whether apparent diffusion coefficients (ADCs) derived
      from diffusion-weighted (DW) magnetic resonance (MR) imaging at 3 T correlate
      with the clinical risk of prostate cancer in patients with tumors that are
      visible on MR images, with MR imaging/transrectal ultrasonography (US) fusion
      guided biopsy as a reference. MATERIALS AND METHODS: Forty-eight consecutive
      patients (median age, 60 years; median serum prostate-specific antigen value, 6.3
      ng/mL) who underwent DW imaging during 3-T MR imaging with an endorectal coil
      were included in this retrospective institutional review board-approved study,
      and informed consent was obtained from each patient. Patients underwent targeted
      MR imaging/transrectal US fusion-guided prostate biopsy. Mean ADCs of cancerous
      target tumors were correlated with Gleason and D'Amico clinical risk scores. The
      true risk group rate and predictive value of the mean ADC for classifying a tumor
      by its D'Amico clinical risk score was determined by using linear discriminant
      and receiver operating characteristic analyses. RESULTS: A significant negative
      correlation was found between mean ADCs of tumors in the peripheral zone and
      their Gleason scores (P = .003; Spearman rho = -0.60) and D'Amico clinical risk
      scores (P < .0001; Spearman rho = -0.69). ADC was found to distinguish tumors in
      the peripheral zone with intermediate to high clinical risk from those with low
      clinical risk with a correct classification rate of 0.73. CONCLUSION: There is a
      significant negative correlation between ADCs and Gleason and D'Amico clinical
      risk scores. ADCs may therefore be useful in predicting the aggressiveness of
      prostate cancer. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100667/-/DC1.

PMID- 21177391
TI  - Intracranial dural arteriovenous shunts: transarterial glue embolization-
      experience in 115 consecutive patients.
AB  - PURPOSE: To evaluate the effectiveness and safety of transarterial glue
      embolization of intracranial dural arteriovenous shunts (DAVS). MATERIALS AND
      METHODS: Institutional review board approval was obtained, with waiver of
      informed consent, for this retrospective study. From a single-center database of
      information on 371 intracranial DAVS, data in 115 consecutive patients treated
      with transarterial glue embolization were identified and assessed. Clinical and
      angiographic features, including cure rate, complications, and outcome, were
      evaluated. The treatment results were also compared between the patients in the
      first half of the consecutive series and those in the second half. The mean glue
      concentrations used were compared between the first and second halves of the
      patient series by using the Student t test. RESULTS: One hundred twenty-one
      lesions were treated with transarterial glue embolization. There were 31 (25.6%)
      Borden type I lesions, 39 (32.2%) Borden type II lesions, and 51 (42.1%) Borden
      type III lesions. Angiographic cure with glue embolization was achieved for 36
      lesions (29.8%); 17 (14.0%) lesions were cured immediately, and 19 (15.7%) showed
      progressive thrombosis at follow-up. The angiographic cure rate for Borden type
      III lesions improved from 10% to 55% in the later group of patients as compared
      with the earlier group. The mean concentration of glue was significantly lower in
      the later group of patients. One (0.9%) of the 115 patients suffered permanent
      morbidity from aggravation of left extremity weakness due to venous thrombosis.
      Eight patients experienced nonpermanent morbidities, including transient
      worsening of neurologic status due to venous thrombosis (n = 4), alopecia (n =
      2), scalp ulcer (n = 1), and pulmonary embolism (n = 1). Overall, improvement (n
      = 65) or stabilization (n = 32) of symptoms was seen in 84.3% of the patients.
      CONCLUSION: Transarterial glue embolization is a safe and effective method of
      primary treatment for intracranial DAVS, especially Borden type III lesions.
      Improvement of cure rates in the latter half of this study suggest that technical
      advances and experience may enhance outcomes.

PMID- 21177393
TI  - White matter damage in Alzheimer disease and its relationship to gray matter
      atrophy.
AB  - PURPOSE: To explore the regional patterns of white matter (WM) tract damage in
      (a) patients with probable Alzheimer disease (AD) and (b) patients with amnestic
      mild cognitive impairment (aMCI) and at least one abnormal biomarker and to
      investigate whether WM damage is related to gray matter (GM) atrophy. MATERIALS
      AND METHODS: This study was approved by the institutional review board, and
      written informed consent was obtained from each participant. Twenty-three
      patients with AD, 15 patients with aMCI, and 15 healthy control subjects
      underwent diffusion tensor magnetic resonance imaging. WM tract damage was
      investigated by using tract-based spatial statistics, and GM atrophy was measured
      by using voxel-based morphometry. RESULTS: Compared with control subjects,
      patients with AD had an increase in mean diffusivity in all major WM tracts
      studied, including the limbic, cortico-cortical, interhemispheric, and
      corticospinal tracts. Conversely, fractional anisotropy decreased only in the
      parahippocampal tract, fornix, and small, inferior parietal regions. In addition,
      patients with AD showed a widespread increase in axial and radial diffusivity
      compared with control subjects. Patients with aMCI showed an increase in axial
      diffusivity only in tracts projecting to the frontal cortex and splenium of the
      corpus callosum. Significant and anatomically congruent correlations between WM
      changes and regional GM atrophy were found in patients with AD. Conversely,
      damage to most WM tracts in patients with aMCI did not correlate with GM atrophy.
      CONCLUSION: In AD, the observed patterns of WM abnormalities may reflect the
      advanced phase of a secondary degenerative process and an association, especially
      in the early phases of the disease, with primary WM tract damage over and above
      GM abnormalities.

PMID- 21177392
TI  - Cartilage in anterior cruciate ligament-reconstructed knees: MR imaging T1{rho}
      and T2--initial experience with 1-year follow-up.
AB  - PURPOSE: To longitudinally evaluate cartilage matrix changes by using magnetic
      resonance (MR) imaging T1(rho) (T1 relaxation time in rotating frame) and T2
      quantification and to study the relationship between meniscal damage and
      cartilage degeneration in anterior cruciate ligament (ACL)-reconstructed knees.
      MATERIALS AND METHODS: This was an institutional review board-approved, HIPAA
      compliant study. Informed consent was obtained. Twelve patients with acute ACL
      injuries were imaged with 3.0-T MR imaging at baseline (after injury and prior to
      ACL reconstruction) and 1 year after ACL reconstruction. Ten age-matched healthy
      subjects were studied as controls. Cartilage T1(rho) and T2 were quantified in
      full thickness, superficial, and deep layers of defined subcompartments at
      baseline and follow-up in ACL-injured knees and were compared with measures
      acquired in matched regions of control knees. Meniscal lesions were graded by
      using modified subscores of the Whole-Organ Magnetic Resonance Imaging Score
      system. RESULTS: T1(rho) values of the posterolateral tibial cartilage in ACL
      injured knees were significantly elevated at baseline compared with T1(rho)values
      of control knees and were not fully recovered at 1-year follow-up. T1(rho) values
      of weight-bearing medial femorotibial cartilage in ACL-injured knees were
      significantly elevated at 1-year follow-up compared with those of control knees.
      No significant differences in T2 values between ACL-injured and control knees
      were found. Patients with lesions in the posterior horn of the medial meniscus
      showed a greater increase of T1(rho) and T2 from baseline to follow-up in
      adjacent cartilage than patients without lesions in the medial meniscus.
      CONCLUSION: Quantitative MR imaging T1(rho) and T2 enable detection of changes in
      the cartilage matrix of ACL-reconstructed knees as early as 1 year after ACL
      reconstruction.

PMID- 21177394
TI  - Use of MR venography for characterization of the extracranial venous system in
      patients with multiple sclerosis and healthy control subjects.
AB  - PURPOSE: To investigate the differences in the extracranial venous system in
      patients with multiple sclerosis (MS) and healthy control (HC) subjects by using
      magnetic resonance (MR) venography. MATERIALS AND METHODS: This HIPAA-compliant,
      prospective study was approved by the local institutional review board, and all
      participants gave informed consent. Fifty-seven patients, 41 (72%) with relapsing
      remitting MS and 16 (28%) with secondary-progressive MS, and 21 HC subjects were
      imaged with a 3-T MR unit by using two-dimensional (2D) time-of-flight (TOF) and
      three-dimensional (3D) time-resolved imaging of contrast kinetics (TRICKS)
      sequences. In addition, six MS patients and six HC subjects underwent two
      sequential MR venographic examinations during 1 week to test image-reimage
      reproducibility. The morphologic features of internal jugular vein flow were
      classified as absent, pinpoint, flattened, crescentic, or ellipsoidal flow. Only
      absent and pinpoint flow were considered abnormal. The flow of the vertebral
      veins was classified as absent or present. The prominence of collateral neck
      veins and venous asymmetries between the left and right sides were assessed.
      Differences among groups were tested with a two-tailed Mann-Whitney two-sample
      rank-sum test. RESULTS: No significant differences in morphologic features of
      flow in the internal jugular veins and vertebral veins were found between MS
      patients and HC subjects in any of the examined MR venographic parameters. No
      differences in asymmetry or prominence were found between MS patients and HC
      subjects. There was modest agreement (kappa = 0.67) between 2D TOF and 3D TRICKS
      sequences. Image-reimage reproducibility showed modest agreement (kappa = 0.66)
      for 2D TOF and low agreement for 3D TRICKS (kappa = 0.33). CONCLUSION: No
      significant differences in the extracranial venous systems between MS patients
      and HC subjects were detected by using MR venography. Standardized guidelines are
      needed to define parameters for the presence of venous anomalies.

PMID- 21177395
TI  - Evaluation of a standardized CT colonography training program for novice readers.
AB  - PURPOSE: To determine how many computed tomographic (CT) colonography training
      studies have to be evaluated by novice readers to obtain an adequate level of
      competence in polyp detection. MATERIALS AND METHODS: The study was approved by
      the Institutional Review Board. Informed consent was obtained from all
      participants. Six physicians (one radiologist, three radiology residents, two
      researchers) and three technicians completed a CT colonography training program.
      Two hundred CT colonographic examinations with colonoscopic verification were
      selected from a research database, with 100 CT colonographic examinations with at
      least one polyp 6 mm or larger. After a lecture session and short individual
      hands-on training, CT colonography training was done individually with immediate
      feedback of colonoscopy outcome. Per-polyp sensitivity was calculated for four
      sets of 50 CT colonographic examinations for lesions 6 mm or larger. By using
      logistic regression analyses, the number of CT colonographic examinations to
      reach 90% sensitivity for lesions 6 mm or larger was estimated. Reading times
      were registered. RESULTS: The average per-polyp sensitivity for lesions 6 mm or
      larger was 76% (207 of 270) in the first set of 50 CT colonographic examinations,
      77% (262 of 342) in the second (P = .96 vs first set), 80% (310 of 387) in the
      third (P = .67 vs first set), and 91% (261 of 288) in the fourth (P = .018). The
      estimated number of CT colonographic examinations for a sufficient sensitivity
      was 164. Six of nine readers reached this level of competence within 175 CT
      colonographic examinations. Reading times decreased significantly from the first
      to the second set of 50 CT colonographic examinations for six readers.
      CONCLUSION: Novice CT colonography readers obtained sensitivity equal to that of
      experienced readers after practicing on average 164 CT colonographic studies.

PMID- 21177396
TI  - Breast cancer: early- and late-fluorescence near-infrared imaging with
      indocyanine green--a preliminary study.
AB  - PURPOSE: To assess early- and late-fluorescence near-infrared imaging,
      corresponding to the vascular (early-fluorescence) and extravascular (late
      fluorescence) phases of indocyanine green (ICG) enhancement, for breast cancer
      detection and benign versus malignant breast lesion differentiation. MATERIALS
      AND METHODS: The study was approved by the ethical review board; all participants
      provided written informed consent. Twenty women with 21 breast lesions were
      examined with near-infrared imaging before, during, and after intravenous
      injection of ICG. Absorption and fluorescence projection mammograms were recorded
      simultaneously on a prototype near-infrared imaging unit. Two blinded readers
      independently assessed the images and assigned visibility scores to lesions seen
      on the absorption and absorption-corrected fluorescence mammograms. Imaging
      results were compared with histopathologic findings. Lesion contrast and diameter
      on the fluorescence mammograms were measured, and Cohen kappa, Mann-Whitney U,
      and Spearman rho tests were conducted. RESULTS: The absorption-corrected
      fluorescence ratio mammograms showed high contrast (contrast value range, 0.25
      0.64) between tumors and surrounding breast tissue. Malignant lesions were
      correctly defined in 11 (reader 1) and 12 (reader 2) of 13 cases, and benign
      lesions were correctly defined in six (reader 1) and five (reader 2) of eight
      cases with late-fluorescence imaging. Lesion visibility scores for malignant and
      benign lesions were significantly different on the fluorescence ratio mammograms
      (P = .003) but not on the absorption mammograms (P = .206). Mean sensitivity and
      specificity reached 92% +/- 8 (standard error of mean) and 75% +/- 16,
      respectively, for fluorescence ratio imaging compared with 100% +/- 0 and 25% +/-
      16, respectively, for conventional mammography alone. CONCLUSION: Preliminary
      data suggest that early- and late-fluorescence ratio imaging after ICG
      administration can be used to distinguish malignant from benign breast lesions.

PMID- 21177399
TI  - Residential and health care transition patterns among older medicare
      beneficiaries over time.
AB  - PURPOSE: To describe annual care transition patterns across residential and
      health care settings and assess consistency in care transition patterns across
      years. DESIGN AND METHODS: This retrospective cohort study used the Medicare
      Current Beneficiary Survey (2000-2005). The sample comprised beneficiaries aged
      65 years and older (N = 57,684 person-years of observation). We defined annual
      care transition patterns by combining 4 types of settings: C (community), F
      (facility), S (skilled nursing facility-SNF), and H (hospital). We compared
      weighted frequencies of transition patterns across years. We counted
      repeated/multiple transitions that involved movement into hospital and SNF
      settings and compared them by demographic characteristics. RESULTS: Care
      transition patterns remained consistent from year to year. Approximately 22% of
      the study population experienced a transition annually. The most frequent
      transition pattern was transition to the hospital and back. Care transition
      patterns were enormously heterogeneous with more than 230 unique patterns;
      approximately 1 in 4 community-dwelling (~23%) and most facility-dwelling (~60%)
      beneficiaries with at least one transition had a unique transition pattern.
      Beneficiaries residing in a facility were more likely to undergo multiple
      transitions to hospitals and SNFs compared with community-dwelling beneficiaries.
      IMPLICATIONS: The study provides a description of annual care transition patterns
      across six years. Knowledge of the consistency of care transition patterns may
      serve as a baseline from which to compare future patterns and aid in designing
      interventions targeted at specific transitions.

PMID- 21177400
TI  - Detection and investigation of invasive mould disease.
AB  - A comprehensive review of diagnostic techniques for opportunistic systemic
      mycoses focused on invasive mould disease in immunocompromised patients is
      presented. We first analysed conventional diagnostic methods, such as microscopy
      examination, culture and radiology, underlining their limitations, which have led
      to the development of alternative methods, such as the detection of fungal
      components. Among these we highlight fungal antigen and DNA quantification, which
      make it possible to detect infections early and start appropriate treatment. We
      also briefly review the methods for carrying out susceptibility tests for
      antifungal drugs, including reference procedures, commercial techniques and their
      indications. Furthermore, we analyse the recommendations for therapeutic drug
      monitoring of antifungal agents in body fluids.

PMID- 21177401
TI  - Systematic review and mixed treatment comparison of randomized evidence for
      empirical, pre-emptive and directed treatment strategies for invasive mould
      disease.
AB  - Randomized controlled trials (RCTs) provide the most reliable estimates of the
      effects of treatments. However, not all treatments are compared in available
      RCTs, making comparison of treatments problematic. Mixed treatment comparisons
      (MTCs) can provide estimates of the comparative effects of treatments across a
      range of available therapeutic options. MTCs use networks of available direct
      comparisons to estimate differences in treatments that have not been estimated in
      trials via a common comparator. We conducted a systematic review and MTCs of
      comparative RCTs in haematological patients of anti-mould active agents used for
      the empirical treatment of febrile neutropenia (Analysis 1), and pre-emptive
      therapy (Analysis 2) of invasive mould diseases. In addition, we summarized the
      evidence available associated with the use of directed treatment strategies
      (Analysis 3). For empirical therapy, caspofungin proved superior to amphotericin
      B, liposomal amphotericin B, amphotericin B lipid complex and voriconazole in the
      outcome of survival, but no agents showed superiority for treatment response.
      There was no evidence of a difference between pre-emptive and empirical
      strategies on mortality outcomes. For directed therapy, voriconazole was superior
      to amphotericin B for overall survival, and both voriconazole and liposomal
      amphotericin B were superior to amphotericin B and amphotericin B colloidal
      dispersion on the outcome of response. While limited to some degree by the
      availability of RCTs, the MTCs reported here provide the best available evidence
      of relative therapeutic success for different available treatment strategies.

PMID- 21177402
TI  - Treatment and timing in invasive mould disease.
AB  - Invasive mould disease is a growing threat for immunocompromised patients. The
      optimum time to use mould-active antifungal agents is much debated. Current
      approaches to antifungal prophylaxis, early treatment (empirical and pre-emptive
      therapy) and treatment of documented mould infections in onco-haematology
      patients are discussed.

PMID- 21177403
TI  - Optimizing management of invasive mould diseases.
AB  - We describe an integrated care pathway (ICP) for the optimal management of
      invasive mould disease (IMD). The ICP is for use by health professionals involved
      in the care of patients with haematological malignancies and haematopoietic stem
      cell transplant recipients who are at increased risk of IMD. The ICP is not
      intended for use in other patient groups where the evidence base is more limited.
      The ICP involves the patient and their carers, as well as describing the roles
      and the complex interaction of healthcare professionals in different departments.
      Therefore, the management of IMD as described in the ICP must be appropriate for
      the overall organization, and will be dependent on the facilities [e.g. high
      efficiency particulate air (HEPA) filtration] and services available. The ICP
      deals with risk stratification, diagnostic tests, prophylactic and treatment
      strategies and how to incorporate these into the ICP. Outpatient drug management
      after hospital discharge and cessation of therapy are outlined. Local
      implementation of this ICP will vary from centre to centre: the ICP is a generic
      template for guidance indicating the requirements for optimal IMD management and
      as such provides a standard against which local practice can be audited. For
      clinical governance, to minimize variation in practice and, ultimately, to
      improve patient outcomes, each centre should regularly monitor and document
      compliance with the local ICP, from provision of patient information, appropriate
      prescribing and diagnostic investigation to clinical outcomes.

PMID- 21177404
TI  - Risk assessment and prognostic factors for mould-related diseases in
      immunocompromised patients.
AB  - Invasive fungal diseases are important causes of morbidity and mortality in
      immunocompromised patients. Patients with haematological malignancies and solid
      cancers, as well as those with allogeneic haematopoietic stem cell and solid
      organ transplants, are at high risk of developing such an infection. Many fungi
      can cause invasive disease, with Aspergillus spp. and Candida spp. being the
      prevalent fungal pathogens infecting susceptible patients. During the past few
      years, rare moulds (for example Zygomycetes and Fusarium spp.) have come into
      focus as the cause of devastating clinical disease. This review aims to analyse
      environmental factors and parameters related to impairment of the immune system
      that are thought to favour the onset of invasive mould infections. Some moulds
      are quite common among all categories of patients, while others appear to be
      limited to a given subset of patients, such as allogeneic haematopoietic stem
      cell or solid organ transplant recipients. In addition to an exploration of
      factors that predispose patients to the acquisition of an invasive mould
      infection, prognostic factors that help to predict the eventual outcome of these
      infections are identified.

PMID- 21177405
TI  - Managing invasive fungal infections: relying on clinical instincts or on a
      rational navigation system?
AB  - The management of invasive fungal disease in the immunocompromised host is
      complex and requires the specialized knowledge of physicians whose primary
      interest is actually the underlying disease rather than infectious complications.
      This Supplement aims to provide these physicians with some tools that may help to
      guide them through the maze of suspicion that an invasive fungal disease is
      present by offering an integrated care pathway of rational patient management.
      Such pathways will inevitably vary in detail in different centres and depend for
      their success on the presence of multidisciplinary teams and an explicit
      agreement on at least the minimum requirements for effective management. The
      integrated care pathways presented constitute an objective instrument to allow
      regular audits for recognizing opportunities to change practice if and when
      weaknesses are identified.

PMID- 21177406
TI  - Serum soluble mesothelin concentrations in malignant pleural mesothelioma:
      relationship to tumor volume, clinical stage and changes in tumor burden.
AB  - PURPOSE: To examine the clinical utility of soluble mesothelin in patients with
      malignant pleural mesothelioma. EXPERIMENTAL DESIGN: A total of 97 patients
      (female: 11; male: 86) were prospectively enrolled, longitudinal serum samples
      collected, and mesothelin concentrations determined. Baseline mesothelin levels
      were analyzed relative to tumor stage, presence of metastatic disease, the
      positron emission tomography (PET) parameters maximum standardized uptake value,
      tumor volume, total glycolytic volume, and survival. Changes in mesothelin level
      were correlated to objective response to chemotherapy, as assessed radiologically
      and by PET imaging, and with patient survival. RESULTS: Baseline mesothelin
      levels greater than 5 nmol/L were a significant negative prognostic indicator (HR
      = 2.25; 95% CI, 1.20-4.21) and correlated with tumor stage and volume. In 55
      patients who received chemotherapy, change in mesothelin correlated with
      radiological response (chi(2) = 11.32; P = 0.023) and change in metabolically
      active tumor volume (r = 0.58; P < 0.01). Median survival for patients with a
      reduction in mesothelin following chemotherapy (19 months) was significantly
      longer than for patients with increased mesothelin (5 months; P < 0.001).
      CONCLUSION: These findings show the potential value of changes in mesothelin
      levels for prognostication and monitoring of treatment response in mesothelioma.

PMID- 21177407
TI  - Excision repair cross-complementing group 1 may predict the efficacy of
      chemoradiation therapy for muscle-invasive bladder cancer.
AB  - PURPOSE: Chemoradiation therapy (CRT) is now widely recognized as bladder
      preserving therapy for muscle-invasive bladder cancer (MIBC). However, some
      patients who fail CRT may miss the chance to be cured by cystectomy. Therefore,
      it is important to select patients with MIBC who are expected to have a good
      response to CRT. Several reports indicate that the excision repair cross
      complementing group 1 (ERCC1) gene is associated with resistance to cisplatin and
      radiation therapy. In this study, we examined the correlation between ERCC1 and
      CRT in vitro and in vivo in bladder cancer. EXPERIMENTAL DESIGN: Bladder cancer
      cell lines T24, 5637, Cl8-2 (multidrug-resistant subline of T24), and CDDP10-3
      (cisplatin-resistant subline of T24) were used for in vitro assays to measure
      ERCC1 expression level and growth inhibition with cisplatin or ionizing radiation
      (IR). We then examined by immunohistochemistry that whether ERCC1 nuclear
      staining correlates with the efficacy of CRT using cisplatin in 22 patients with
      MIBC. RESULTS: Cl8-2 cells expressed ERCC1 mRNA 5.96-fold higher than did T24.
      Cl8-2 and CDDP10-3 were more resistant to cisplatin or IR than was T24.
      Resistance to IR, but not to cisplatin, was removed by suppressing ERCC1 using
      siRNA in both Cl8-2 and CDDP10-3 cells. In immunohistochemistry with ERCC1, 6 of
      8 positive cases did not have complete response to CRT, whereas 12 of 14 negative
      cases had complete response. Sensitivity and specificity were 75% and 85.7%,
      respectively (P = 0.008). CONCLUSION: Although further study is needed, ERCC1
      expression level may predict the efficacy of CRT for MIBC.

PMID- 21177409
TI  - Notch pathway inhibition significantly reduces rhabdomyosarcoma invasiveness and
      mobility in vitro.
AB  - PURPOSE: Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in
      children and can be divided into two main subtypes: embryonal and alveolar RMS.
      Patients with metastatic disease continue to have very poor prognosis although
      aggressive therapies and recurrences are common in advanced localized disease.
      The oncogenic potential of the Notch pathway has been established in some cancers
      of the adult and in some pediatric malignancies. EXPERIMENTAL DESIGN: A real-time
      PCR assay was used to ascertain the expression of several Notch pathway
      components in a wide panel of RMS and cell lines. Four gamma-secretase inhibitors
      (GSIs) were tested for pathway inhibition and the degree of inhibition was
      assessed by analysis of Hes1 and Hey1 expression. The putative effects of Notch
      pathway inhibition were evaluated by wound-healing, matrigel/transwell invasion,
      cell-cycle, and apoptosis assays. RESULTS: The Notch pathway was widely expressed
      and activated in RMS and underwent substantial inhibition when treated with GSIs
      or transfected with a dominant negative form of MAML1. RMS cells showed a
      significant decrease in its mobility and invasiveness when the Notch pathway was
      properly inhibited; conversely, its inhibition had no noticeable effect on cell
      cycle or apoptosis. CONCLUSION: Pharmacological or genetic blockage of the
      pathway significantly reduced invasiveness of RMS cell lines, thereby suggesting
      a possible role of the Notch pathway in the regulation of the metastatic process
      in RMS.

PMID- 21177408
TI  - Evaluation of the anti-HER2 C6.5 diabody as a PET radiotracer to monitor HER2
      status and predict response to trastuzumab treatment.
AB  - PURPOSE: The rapid tumor targeting and pharmacokinetic properties of engineered
      antibodies make them potentially suitable for use in imaging strategies to
      predict and monitor response to targeted therapies. This study aims to evaluate
      C6.5 diabody (C6.5 db), a noncovalent anti-HER2 single-chain Fv dimer, as a
      radiotracer for predicting response to HER2-targeted therapies such as
      trastuzumab. EXPERIMENTAL DESIGN: Immunodeficient mice bearing established HER2
      positive tumor xenografts were injected with radioiodinated C6.5 db and imaged by
      PET/CT. Radiotracer biodistribution was quantified by biopsied tumor and normal
      tissues. Potential competition between trastuzumab and C6.5 db was examined in
      vitro by flow cytometry and coimmunoprecipitations. RESULTS: Biodistribution
      analysis of mice bearing xenografts with varying HER2 density revealed that the
      tumor uptake of (125)I-C6.5 db correlates with HER2 tumor density. In vitro
      competition experiments suggest that the C6.5 db targets an epitope on HER2 that
      is distinct from that bound by trastuzumab. Treatment of mice affected with SK-OV
      3 tumor with trastuzumab for 3 days caused a 42% (P = 0.002) decrease in tumor
      uptake of (125)I-C6.5 db. This is consistent with a dramatic decrease in the
      tumor PET signal of (124)I-C6.5 db after trastuzumab treatment. Furthermore, mice
      affected with BT-474 tumor showed an approximately 60% decrease (P = 0.0026) in
      C6.5 db uptake after 6 days of trastuzumab treatment. Immunohistochemistry of
      excised xenograft sections and in vitro flow cytometry revealed that the
      decreased C6.5 db uptake on trastuzumab treatment is not associated with HER2
      downregulation. CONCLUSIONS: These studies suggest that (124)I-C6.5 db-based
      imaging can be used to evaluate HER2 levels as a predictor of response to HER2
      directed therapies.

PMID- 21177410
TI  - Chondroitinase ABC I-mediated enhancement of oncolytic virus spread and antitumor
      efficacy.
AB  - PURPOSE: The inhibitory role of secreted chondroitin sulfate proteoglycans on
      oncolytic viral (OV) therapy was examined. Chondroitinase ABC (Chase-ABC) is a
      bacterial enzyme that can remove chondroitin sulfate glycosaminoglycans from
      proteoglycans without any deleterious effects in vivo. We examined the effect of
      Chase-ABC on OV spread and efficacy. EXPERIMENTAL DESIGN: Three-dimensional
      glioma spheroids placed on cultured brain slices were utilized to evaluate OV
      spread. Replication-conditional OV-expressing Chase-ABC (OV-Chase) was engineered
      using HSQuik technology and tested for spread and efficacy in glioma spheroids.
      Subcutaneous and intracranial glioma xenografts were utilized to compare
      antitumor efficacy of OV-Chase, rHsvQ (control), and PBS. Titration of viral
      particles was performed from OV-treated subcutaneous tumors. Glioma invasion was
      assessed in collagen-embedded glioma spheroids in vitro and in intracranial
      tumors. All statistical tests were two sided. RESULTS: Treatment with Chase-ABC
      in cultured glioma cells significantly enhanced OV spread in glioma spheroids
      grown on brain slices (P < 0.0001). Inoculation of subcutaneous glioma xenografts
      with Chase-expressing OV significantly increased viral titer (>10 times, P =
      0.0008), inhibited tumor growth, and significantly increased overall animal
      survival (P < 0.006) compared with treatment with parental rHsvQ virus. Single OV
      Chase administration in intracranial xenografts also resulted in longer median
      survival of animals than rHsvQ treatment (32 vs. 21 days, P < 0.018). Glioma cell
      migration and invasion were not increased by OV-Chase treatment. CONCLUSIONS: We
      conclude that degradation of glioma extracellular matrix with OV-expressing
      bacterial Chase-ABC enhanced OV spread and antitumor efficacy.

PMID- 21177411
TI  - Pathologic reassessment of prostate cancer surgical specimens before molecular
      retrospective studies.
AB  - PURPOSE: The retrospective use of prostate cancer tissue is crucial to design
      tumor marker prognostic studies. We hypothesize that comparison between recent
      and more historical cases could introduce biases due to stage and grade migration
      upon time. DESIGN: We reviewed 544 margin-free specimens from patients treated
      for clinically localized prostate cancer by radical prostatectomy between 2000
      and 2005. One hundred and ninty-two patients that underwent biochemical
      recurrence after surgery were matched with 352 patients without progression,
      according to pretreatment prostate specific antigen, Gleason score, pathologic
      stage, and follow-up duration (at least 36 months). RESULTS: The reassessment led
      to histopathologic reclassification of standard prognostic variables in 15% of
      cases, including modifications in the Gleason score (n = 63), pathologic stage (n
      = 12), and margin status (n = 30). Most discrepancies with the initial reports
      are explained either by differences in the scoring system upon time, or by the
      exam of additional tissues sections. The impact of reclassification led to
      increase adverse prognostic factors more frequently in the group of patients with
      progression (Chi(2), P < 0.0001). CONCLUSION: Careful reassessment of prostate
      cancer samples should be mandatory before molecular prognostic studies to ensure
      a more uniform pathologic evaluation, and might be reported in the
      "recommendations for tumor markers prognostic studies" (REMARK).

PMID- 21177412
TI  - Frequency of circulating Tregs with demethylated FOXP3 intron 1 in melanoma
      patients receiving tumor vaccines and potentially Treg-depleting agents.
AB  - PURPOSE: Regulatory T cells (Tregs) are thought to inhibit antitumor immune
      responses, and their depletion could therefore have a synergistic effect with
      therapeutic cancer vaccines. We investigated the impact of three medications on
      blood Treg frequency in vaccinated cancer patients. EXPERIMENTAL DESIGN: To date,
      the most specific marker for human Tregs is demethylation in the DNA that encodes
      the transcription factor FOXP3. Thus, we used a FOXP3 methylation-specific
      quantitative PCR assay (MS-qPCR) to measure Treg frequencies in the peripheral
      blood mononuclear cells (PBMCs) of melanoma patients. The patients participated
      in three clinical trials that combined tumor vaccines with potential Treg
      depleting agents: low-dose cyclophosphamide, anti-CD25 monoclonal antibody
      daclizumab, and the IL-2/diphtheria toxin fusion protein denileukin diftitox.
      RESULTS: In the nine control patients, blood Treg frequencies varied over time;
      there was a 46% reduction in one patient. In treated patients, a more than 2-fold
      decrease in Tregs was observed in one out of 11 patients receiving
      cyclophosphamide and in four out of 13 receiving daclizumab, but there was no
      such Treg decrease in any of the six patients who received denileukin diftitox.
      As a positive control, a more than 2-fold increase in blood Tregs was detected in
      four out of nine patients who were treated with interleukin-2. CONCLUSIONS: We
      used a MS-qPCR method that detects Tregs but not other activated T lymphocytes;
      however, none of the Treg-depleting strategies that we tested led, in the
      majority of patients, to a conservative 50% reduction in blood Tregs.

PMID- 21177413
TI  - Molecular dissection of dual pseudosymmetric solute translocation pathways in
      human P-glycoprotein.
AB  - The human multispecific drug efflux transporter P-glycoprotein (P-gp) causes drug
      resistance and modulates the pharmacological profile of systemically administered
      medicines. It has arisen from a homodimeric ancestor by gene duplication. Crystal
      structures of mouse MDR1A indicate that P-gp shares the overall architecture with
      two homodimeric bacterial exporters, Sav1866 and MsbA, which have complete
      rotational symmetry. For ATP-binding cassette transporters, nucleotide binding
      occurs in two symmetric positions in the motor domains. Based on the homology
      with entirely symmetric half-transporters, the present study addressed the key
      question: can biochemical evidence for the existence of dual drug translocation
      pathways in the transmembrane domains of P-gp be found? P-gp was photolabeled
      with propafenone analogs, purified, and digested proteolytically, and peptide
      fragments were identified by high-resolution mass spectrometry. Labeling was
      assigned to two regions in the protein by projecting data into homology models.
      Subsequently, symmetric residue pairs in the putative translocation pathways were
      identified and replaced by site-directed mutagenesis. Transport assays
      corroborated the existence of two pseudosymmetric translocation pathways.
      Although rhodamine123 has a preference to take one path, verapamil, propafenones,
      and vinblastine preferentially use the other. Two major findings ensued from this
      study: the existence of two solute translocation pathways in P-gp as a reflection
      of evolutionary origin from a homodimeric ancestor and selective but not
      exclusive use of one of these pathways by different P-gp solutes. The
      pseudosymmetric behavior reconciles earlier kinetic and thermodynamic data,
      suggesting an alternative concept of drug transport by P-gp that will aid in
      understanding the off-target quantitative structure activity relationships of P
      gp interacting drugs.

PMID- 21177414
TI  - Celecoxib antagonizes the cytotoxicity of cisplatin in human esophageal squamous
      cell carcinoma cells by reducing intracellular cisplatin accumulation.
AB  - High cyclooxygenase 2 (COX-2) expression has been reported to be clinically
      associated with reduced cisplatin-based therapy efficacy in esophageal cancer.
      However, the benefit of including COX-2-selective inhibitors in therapeutic
      regimens remains uncertain. Thus, we sought to determine the effects of COX
      inhibitors on the cytotoxicity of cisplatin and to further explore the mechanism
      involved in human esophageal squamous cell carcinoma cells. Among the four tested
      COX inhibitors [celecoxib, 4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1
      yl]benzenesulfonamide (SC-236), nimesulide, and indomethacin], all of which
      substantially suppressed prostaglandin E(2) production to a similar extent; only
      the COX-2-selective inhibitors celecoxib and SC-236 antagonized cisplatin-induced
      cytotoxicity and apoptosis in both cisplatin-resistant cells and their wild-type
      counterparts. Knockdown of COX-2 by small interference RNA failed to mimic the
      antagonizing effects of celecoxib and SC-236, implying that their action is COX-2
      independent. Further mechanistic analysis revealed that the antagonizing effect
      of celecoxib and SC-236 on cytotoxic action of cisplatin was associated with
      decreased whole-cell cisplatin accumulation and DNA platination. Reduced influx,
      accompanied by the reduction of protein level of copper transporter 1, accounts
      for decreased intracellular cisplatin accumulation. In addition, combined
      treatment did not elicit greater antitumor activity than cisplatin or celecoxib
      monotherapy in vivo in an esophageal cancer xenograft model. Collectively, these
      data demonstrate that celecoxib antagonizes the cytotoxicity of cisplatin by
      decreasing intracellular cisplatin and DNA platination. The combination treatment
      also shows no beneficial effect compared with cisplatin or celecoxib monotherapy
      in vivo. Therefore, current clinical trials with celecoxib in combination with
      cisplatin should be approached with caution.

PMID- 21177415
TI  - Identification and mechanism of action of the acylguanidine MRT-83, a novel
      potent Smoothened antagonist.
AB  - There is a clear need to develop novel pharmacological tools to improve our
      understanding of Smoothened (Smo) function in normal and pathological states.
      Here, we report the discovery, the mechanism of action, and the in vivo activity
      of N-(2-methyl-5-(3-(3,4,5-trimethoxybenzoyl)guanidino)phenyl)biphenyl-4
      carboxamide (MRT-83), a novel potent antagonist of Smo that belongs to the
      acylguanidine family of molecules. MRT-83 fits to a proposed pharmacophoric model
      for Smo antagonists with three hydrogen bond acceptor groups and three
      hydrophobic regions. MRT-83 blocks Hedgehog (Hh) signaling in various assays with
      an IC50 in the nanomolar range, showing greater potency than the reference Smo
      antagonist cyclopamine. MRT-83 inhibits Bodipy-cyclopamine binding to human and
      mouse Smo but does not modify Wnt signaling in human embryonic kidney 293
      transiently transfected with a Tcf/Lef-dependent Firefly luciferase reporter
      together with a Renilla reniformis luciferase control reporter. MRT-83 abrogates
      the agonist-induced trafficking of endogenous mouse or human Smo to the primary
      cilium of C3H10T1/2 or NT2 cells that derive from a pluripotent testicular
      carcinoma. Stereotaxic injection into the lateral ventricle of adult mice of MRT
      83 but not of a structurally related compound inactive at Smo abolished up
      regulation of Patched transcription induced by Sonic Hedgehog in the neighboring
      subventricular zone. These data demonstrate that MRT-83 efficiently antagonizes
      Hh signaling in vivo. All together, these molecular, functional and biochemical
      studies provide evidence that MRT-83 interacts with Smo. Thus, this novel Smo
      antagonist will be useful for manipulating Hh signaling and may help develop new
      therapies against Hh-pathway related diseases.

PMID- 21177417
TI  - What should we be fine tuning in acute coronary syndromes--dosing of antiplatelet
      therapy or data presentation?
AB  - The CURRENT OASIS 7 (The Clopidogrel and Aspirin Optimal Dose Usage to Reduce
      Recurrent Events-Seventh Organization to Assess Strategies in Ischemic Syndromes)
      trial recently published in the New England Journal of Medicine and a subgroup of
      this trial published in The Lancet evaluated alternative dosing strategies for
      clopidogrel and aspirin in the treatment of acute coronary syndromes. Critiques
      of these clinical trial data have been previously published and debated, but this
      study brings to light another area of scientific discussion. Using this trial as
      an example, this commentary emphasizes several key aspects of the clinical trial
      data presentation and publication process that need to improve and reminds
      clinicians of the many limitations to subgroup analyses.

PMID- 21177418
TI  - Defining reality: the potential role of pharmacists in assessing the impact of
      progesterone receptor modulators and misoprostol in reproductive health.
AB  - Medical abortion is increasingly heralded as an ideal method for decreasing
      maternal mortality in health-care resource-deprived areas and as an answer to the
      shrinking pool of physicians willing to perform abortions. The advent of
      progesterone receptor modulators (PRMs) and the recent approval by the Food and
      Drug Administration of ella (ulipristal) as an emergency contraceptive put
      pharmacists in the center of abortion controversy. Pharmacists, worldwide, need
      to be aware of the controversy surrounding the introduction of PRMs, particularly
      with regard to the effect on health policy, their mechanism of action, associated
      adverse events, and common off-label uses. Once understood, genuine opportunity
      exists for pharmacists to serve a fundamental role in positively shaping public
      health policy.

PMID- 21177419
TI  - Central nervous system toxicity associated with ertapenem use.
AB  - OBJECTIVE: To report stroke-like symptoms and unusual central nervous system
      adverse effects in 2 elderly patients receiving ertapenem. CASE SUMMARY: Two
      patients >=70 years of age experienced unusual mental status changes while
      receiving ertapenem. Patient 1 developed garbled speech and miosis 1 week after
      starting appropriately dosed ertapenem (1 g/day) for sacral osteomyelitis.
      Symptoms resolved upon ertapenem discontinuation but recurred upon rechallenge.
      Patient 2, a cachectic male with acute renal insufficiency, became delirious and
      progressively obtunded 5 days after starting ertapenem 1 g/day. Nine days after
      initiation of therapy, he required intubation and mechanical ventilation;
      ertapenem was discontinued at that time. Within 2 days of ertapenem
      discontinuation, his mental state cleared and the ventilator was removed.
      DISCUSSION: Carbapenems, including ertapenem, have been implicated in causing
      central nervous system toxicity, including hallucinations and seizures. However,
      published reports of other, nonseizure-related central nervous system events are
      limited. Considerable resources were expended on extensive medical interventions
      before ertapenem was identified as a potential cause of the delirium in our
      patients. When applied to our patients, the Naranjo probability scale indicated a
      highly probable relationship for patient 1 and a probable relationship for
      patient 2 between the adverse effects and ertapenem use. CONCLUSIONS: Clinicians
      should be cognizant of ertapenem's potential to induce profound changes in mental
      status that may mimic other conditions in elderly patients.

PMID- 21177420
TI  - Coma after overdose with duloxetine.
AB  - OBJECTIVE: To describe a case of a patient who became comatose after taking an
      overdose of duloxetine, a serotonin-norepinephrine reuptake inhibitor. CASE
      SUMMARY: A 49-year-old male ingested an overdose of duloxetine approximately 2
      hours before presentation to the emergency department. On arrival he was drowsy,
      but easily awakened and oriented, with Glasgow Coma Score 14 (eyes 3, motor 6,
      verbal 5). Immediately after admission, charcoal and magnesium sulfate were given
      to prevent further systemic absorption of medication through the gastrointestinal
      tract. No gastric lavage was performed. Six hours after drug intake the patient
      became unconscious (Glasgow Coma Score 7, eyes 2, motor 4, verbal 1). Full
      toxicologic screening showed a toxic duloxetine plasma concentration of 0.86
      mg/L. The patient was admitted to the intensive care unit (ICU) and, on arrival,
      urinary retention was noted. During ICU admission the patient remained
      hemodynamically stable; approximately 12 hours after ingestion of duloxetine, he
      regained consciousness. Over the next 3 days the urinary output decreased to 60
      mL/day. After 4 days patient was discharged without any remaining symptoms. Based
      on repeated plasma duloxetine serum concentration determinations, a plasma half
      life of duloxetine was calculated to be 18 hours (reference range 9-19).
      DISCUSSION: The Naranjo probability scale suggested that duloxetine was the
      probable cause for the symptoms described. CONCLUSION: Overdose with duloxetine
      can induce coma several hours after intake, with a fast reversal in our case.

PMID- 21177421
TI  - Everolimus: a new mammalian target of rapamycin inhibitor for the treatment of
      advanced renal cell carcinoma.
AB  - OBJECTIVE: To review clinical trials and main characteristics of everolimus, with
      focus on treatment of advanced renal cell carcinoma. DATA SOURCES: Pertinent data
      were identified primarily through a search of MEDLINE and PubMed (1966-November
      2010) using the primary search terms everolimus, RAD001, renal cell carcinoma,
      and mTOR inhibitors. STUDY SELECTION AND DATA EXTRACTION: Studies evaluating the
      safety and efficacy of everolimus in patients with cancer were evaluated,
      including Phase 1, 2, and 3 trials. Preference was given to Phase 2 and 3 studies
      evaluating use of everolimus in patients with renal cell carcinoma. DATA
      SYNTHESIS: Everolimus is an oral mammalian target of rapamycin (mTOR) inhibitor
      approved for the management of patients with advanced renal cell carcinoma who
      progressed on tyrosine kinase inhibitor therapy. Actions of everolimus within the
      mTOR pathway result in decreased protein synthesis and cell cycle arrest, as well
      as decreased angiogenesis. A usual starting dose for patients with renal cell
      carcinoma is 10 mg daily. Everolimus undergoes extensive hepatic metabolism,
      primarily through the CYP3A4 isoenzyme, which predisposes it to drug interactions
      with inducers and inhibitors of this enzyme. Most commonly reported adverse
      events associated with everolimus include anemia, hyperglycemia,
      hypercholesterolemia, mucositis, fatigue, and rash. Approval of everolimus was
      based on the results of a Phase 3 trial that demonstrated an increase in median
      progression-free survival by 2.1 months in patients receiving everolimus therapy
      as compared to placebo. The drug was recently added to the National Comprehensive
      Cancer Network guidelines as a treatment option for patients with advanced renal
      cell carcinoma who have progressed on tyrosine kinase therapy. CONCLUSIONS: Based
      on a review of the currently available literature, everolimus provides a safe and
      efficacious treatment option for patients with renal cell carcinoma who have
      progressed on treatment with sunitinib and/or sorafenib.

PMID- 21177422
TI  - The impact of item clustering on visual search: It all depends on the nature of
      the visual search.
AB  - Decades of vision research on how people search for a target item among
      distractor items have always avoided item clustering. Instead, researchers made
      sure that items were evenly distributed in search displays. This, however, is
      rarely the case in our everyday visual environment. Consequently, it is largely
      unknown how item clustering may impact visual search performance. In this study,
      I manipulated item clustering in search displays. In an easy feature search,
      observers looked for a target letter "T" among distractor letters "Os" and
      reported whether the target was pointing to the left or to the right. In a
      difficult spatial configuration search, observers searched and reported the
      orientation of the target letter "T" among distractor letters "Ls". The two types
      of searches thus had the same target but different distractors. In two
      experiments, I found that while item clustering slowed down the easy feature
      search, it speeded up the difficult spatial configuration search. Together, these
      results show that item clustering significantly affects visual search performance
      and its exact impact (negative or positive) depends on the nature of the visual
      search.

PMID- 21177424
TI  - A case study addressing the reliability of polychlorinated biphenyl levels
      measured at the time of breast cancer diagnosis in representing early-life
      exposure.
AB  - BACKGROUND: To date, breast cancer epidemiologic studies have relied on blood or
      tissue specimens sampled at the time of diagnosis or a few years prior to assess
      lifetime exposure to polychlorinated biphenyls (PCB). In this study, we evaluated
      whether such PCB measurements are indicative of early-life levels by
      reconstructing lifetime toxicokinetic profiles for women included in the CECILE
      case-control study, using a physiologically based pharmacokinetic (PBPK) model.
      METHODS: We simulated lifetime toxicokinetic profiles of PCB-153 for 2,134 French
      women by incorporating information on body weight history, height, pregnancies,
      and breast-feeding in the PBPK model. Oral dose was calculated by considering
      measured blood PCB-153 and the temporal trend of environmental contamination.
      Area under the concentration versus time curve (AUC) for each decade of life and
      maximum blood concentration (C(max)) were compiled and compared with measured
      levels, using Pearson partial correlation analyses adjusting for age at
      diagnosis. RESULTS: When considering all individuals, simulated AUCs correlated
      with measured PCBs, with coefficients ranging from 0.735 to 0.981. The weakest
      correlations were obtained with AUCs for the first decades of life. Stratified
      analyses suggested that breast-feeding reduces the reliability of late-life blood
      levels in representing lifetime exposure. CONCLUSION: Results of this study
      suggest that PCB levels measured at the time of diagnosis do not fully represent
      early-life exposures. IMPACT: PBPK-derived estimates of early-life levels
      circumvent the limitations of current approaches in assessing PCB lifetime
      exposure and may be used to address hypothesized windows of breast vulnerability
      (e.g., puberty) in this population.

PMID- 21177423
TI  - Circulating sex steroids during pregnancy and maternal risk of non-epithelial
      ovarian cancer.
AB  - BACKGROUND: Sex steroid hormones have been proposed to play a role in the
      development of non-epithelial ovarian cancers (NEOC) but so far no direct
      epidemiologic data are available. METHODS: A case-control study was nested within
      the Finnish Maternity Cohort, the world's largest biorepository of serum
      specimens from pregnant women. Study subjects were selected among women who
      donated a blood sample during a singleton pregnancy that led to the birth of
      their last child preceding diagnosis of NEOC. Case subjects were 41 women with
      sex cord stromal tumors (SCST) and 21 with germ cell tumors (GCT). Three
      controls, matching the index case for age, parity at the index pregnancy, and
      date at blood donation were selected (n = 171). OR and 95% CI associated with
      concentrations of testosterone, androstenedione, 17-OH-progesterone,
      progesterone, estradiol, and sex hormone-binding globulin (SHBG) were estimated
      through conditional logistic regression. RESULTS: For SCST, doubling of
      testosterone, androstenedione, and 17-OH-progesterone concentrations were
      associated with about 2-fold higher risk of SCST [ORs and 95% CI of 2.16 (1.25
      3.74), 2.16 (1.20-3.87), and 2.62 (1.27-5.38), respectively]. These associations
      remained largely unchanged after excluding women within 2-, 4-, or 6-year lag
      time between blood donation and cancer diagnosis. Sex steroid hormones
      concentrations were not related to maternal risk of GCT. CONCLUSIONS: This is the
      first prospective study providing initial evidence that elevated androgens play a
      role in the pathogenesis of SCST. IMPACT: Our study may note a particular need
      for larger confirmatory investigations on sex steroids and NEOC.

PMID- 21177425
TI  - Vitamin supplement use during breast cancer treatment and survival: a prospective
      cohort study.
AB  - BACKGROUND: Antioxidants may protect normal cells from the oxidative damage that
      occurs during radiotherapy and certain chemotherapy regimens; however, the same
      mechanism could protect tumor cells and potentially reduce effectiveness of
      cancer treatments. We evaluated the association of vitamin supplement use in the
      first 6 months after breast cancer diagnosis and during cancer treatment with
      total mortality and recurrence. METHODS: We conducted a population-based
      prospective cohort study of 4,877 women aged 20 to 75 years diagnosed with
      invasive breast cancer in Shanghai, China, between March 2002 and April 2006.
      Women were interviewed approximately 6 months after diagnosis and followed up by
      in-person interviews and record linkage with the vital statistics registry.
      RESULTS: During a mean follow-up of 4.1 years, 444 deaths and 532 recurrences
      occurred. Vitamin use shortly after breast cancer diagnosis was associated with
      reduced mortality and recurrence risk, adjusted for multiple lifestyle factors,
      sociodemographics, and known clinical prognostic factors. Women who used
      antioxidants (vitamin E, vitamin C, multivitamins) had 18% reduced mortality risk
      (HR = 0.82, 95% CI: 0.65-1.02) and 22% reduced recurrence risk (HR = 0.78, 95%
      CI: 0.63-0.95). The inverse association was found regardless of whether vitamin
      use was concurrent or nonconcurrent with chemotherapy, but was present only among
      patients who did not receive radiotherapy. CONCLUSIONS: Vitamin supplement use in
      the first 6 months after breast cancer diagnosis may be associated with reduced
      risk of mortality and recurrence. IMPACT: Our results do not support the current
      recommendation that breast cancer patients should avoid use of vitamin
      supplements.

PMID- 21177426
TI  - Smoking concordance in lung and colorectal cancer patient-caregiver dyads and
      quality of life.
AB  - BACKGROUND: Distress may be heightened among members of cancer patient-caregiver
      dyads that are mismatched on smoking status (either the patient or caregiver
      smokes, but the other does not), negatively affecting quality of life (QoL). The
      purpose of this study was to examine associations between patient-caregiver
      smoking concordance, caregiver psychological adjustment, and caregiver and
      patient mental and physical QoL. METHODS: Lung and colorectal patient-caregiver
      dyads (N = 742) were identified from the Cancer Care Outcomes Research and
      Surveillance (CanCORS) and CanCORS Caregiver studies. The majority of the cancer
      patients were male (67.0%) with local (45.6%) or regional (12.9%) disease. The
      majority of the informal caregivers were females (78.6%), under 65 years of age
      (69.6%), and often spouses (57.8%) of the patients. RESULTS: Lung and colorectal
      cancer caregivers, who were members of dyads where one or both members continued
      to smoke, reported worse mental health QoL than nonsmoking dyads. For colorectal
      cancer patients, continuing to smoke when the caregiver did not was associated
      with worse mental health QoL compared with nonsmoking dyads. Dyad smoking was
      less strongly associated with physical QoL for both caregivers and patients.
      CONCLUSION: Results highlight the importance of assessing smoking in both cancer
      patients and their caregivers and referring families to appropriate psychosocial
      and smoking cessation services. IMPACT: This is the first study to show
      associations between cancer patient-caregiver smoking status and QoL for both
      dyad members. Future studies will need to confirm these associations
      longitudinally and investigate potential mechanisms linking dyad smoking and QoL.

PMID- 21177427
TI  - Role for topoisomerase 1 in transcription-associated mutagenesis in yeast.
AB  - High levels of transcription in Saccharomyces cerevisiae are associated with
      increased genetic instability, which has been linked to DNA damage. Here, we
      describe a pGAL-CAN1 forward mutation assay for studying transcription-associated
      mutagenesis (TAM) in yeast. In a wild-type background with no alterations in DNA
      repair capacity, ~50% of forward mutations that arise in the CAN1 gene under high
      transcription conditions are deletions of 2-5 bp. Furthermore, the deletions
      characteristic of TAM localize to discrete hotspots that coincide with 2-4 copies
      of a tandem repeat. Although the signature deletions of TAM are not affected by
      the loss of error-free or error-prone lesion bypass pathways, they are completely
      eliminated by deletion of the TOP1 gene, which encodes the yeast type IB
      topoisomerase. Hotspots can be transposed into the context of a frameshift
      reversion assay, which is sensitive enough to detect Top1-dependent deletions
      even in the absence of high transcription. We suggest that the accumulation of
      Top1 cleavage complexes is related to the level of transcription and that their
      removal leads to the signature deletions. Given the high degree of conservation
      between DNA metabolic processes, the links established here among transcription,
      Top1, and mutagenesis are likely to extend beyond the yeast system.

PMID- 21177429
TI  - Essential "ankle" in the myosin lever arm.

PMID- 21177428
TI  - FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires
      astrocyte sphingosine 1-phosphate receptor 1 (S1P1) modulation.
AB  - Sphingosine 1-phosphate (S1P), a lysophospholipid, has gained relevance to
      multiple sclerosis through the discovery of FTY720 (fingolimod), recently
      approved as an oral treatment for relapsing forms of multiple sclerosis. Its
      mechanism of action is thought to be immunological through an active
      phosphorylated metabolite, FTY720-P, that resembles S1P and alters lymphocyte
      trafficking through receptor subtype S1P(1). However, previously reported
      expression and in vitro studies of S1P receptors suggested that direct CNS
      effects of FTY720 might theoretically occur through receptor modulation on
      neurons and glia. To identify CNS cells functionally contributing to FTY720
      activity, genetic approaches were combined with cellular and molecular analyses.
      These studies relied on the functional assessment, based on clinical score, of
      conditional null mouse mutants lacking S1P(1) in CNS cell lineages and challenged
      by experimental autoimmune encephalomyelitis (EAE), an animal model of multiple
      sclerosis. All conditional null mutants displayed WT lymphocyte trafficking that
      responded normally to FTY720. In marked contrast, EAE was attenuated and FTY720
      efficacy was lost in CNS mutants lacking S1P(1) on GFAP-expressing astrocytes but
      not on neurons. In situ hybridization studies confirmed that astrocyte loss of
      S1P(1) was the key alteration in functionally affected mutants. Reductions in EAE
      clinical scores were paralleled by reductions in demyelination, axonal loss, and
      astrogliosis. Receptor rescue and pharmacological experiments supported the loss
      of S1P(1) on astrocytes through functional antagonism by FTY720-P as a primary
      FTY720 mechanism. These data identify nonimmunological CNS mechanisms of FTY720
      efficacy and implicate S1P signaling pathways within the CNS as targets for
      multiple sclerosis therapies.

PMID- 21177430
TI  - Steric blocking mechanism explains stretch activation in insect flight muscle.

PMID- 21177431
TI  - Topoisomerase 1 provokes the formation of short deletions in repeated sequences
      upon high transcription in Saccharomyces cerevisiae.
AB  - High transcription is associated with genetic instability, notably increased
      spontaneous mutation rates, which is a phenomenon termed Transcription-Associated
      Mutagenesis (TAM). In this study, we investigated TAM using the chromosomal CAN1
      gene under the transcriptional control of two strong and inducible promoters
      (pGAL1 and pTET) in Saccharomyces cerevisiae. Both pTET- and pGAL1-driven high
      transcription at the CAN1 gene result in enhanced spontaneous mutation rates.
      Comparison of both promoters reveals differences in the type of mutagenesis,
      except for short (-2 and -3 nt) deletions, which depend only on the level of
      transcription. This mutation type, characteristic of TAM, is sequence dependent,
      occurring prefentially at di- and trinucleotides repeats, notably at two
      mutational hotspots encompassing the same 5'-ACATAT-3' sequence. To explore the
      mechanisms underlying the formation of short deletions in the course of TAM, we
      have determined Can(R) mutation spectra in yeast mutants affected in DNA
      metabolism. We identified topoisomerase 1-deficient strains (top1Delta) that
      specifically abolish the formation of short deletions under high transcription.
      The rate of the formation of (-2/-3nt) deletions is also reduced in the absence
      of RAD1 and MUS81 genes, involved in the repair of Top1p-DNA covalent complex.
      Furthermore ChIP analysis reveals an enrichment of trapped Top1p in the CAN1 ORF
      under high transcription. We propose a model, in which the repair of trapped
      Top1p-DNA complexes provokes the formation of short deletion in S. cerevisiae.
      This study reveals unavoidable conflicts between Top1p and the transcriptional
      machinery and their potential impact on genome stability.

PMID- 21177432
TI  - Congruences for the Andrews spt function.
AB  - Ramanujan-type congruences for the Andrews spt(n) partition function have been
      found for prime moduli 5 <= l <= 37 in the work of Andrews [Andrews GE, (2008) J
      Reine Angew Math 624:133-142] and Garvan [Garvan F, (2010) Int J Number Theory
      6:1-29]. We exhibit unexpectedly simple congruences for all l>=5. Confirming a
      conjecture of Garvan, we show that if l>=5 is prime and (-delta/l) = 1, then
      spt[(l2(ln+delta)+1)/24] = 0 (mod l). This congruence gives (l - 1)/2 arithmetic
      progressions modulo l(3) which support a mod l congruence. This result follows
      from the surprising fact that the reduction of a certain mock theta function
      modulo l, for every l>=5, is an eigenform of the Hecke operator T(l(2)).

PMID- 21177433
TI  - Mild oxidative stress activates Nrf2 in astrocytes, which contributes to
      neuroprotective ischemic preconditioning.

PMID- 21177434
TI  - Esterified eicosanoids are acutely generated by 5-lipoxygenase in primary human
      neutrophils and in human and murine infection.
AB  - 5-Lipoxygenase (5-LOX) plays key roles in infection and allergic responses.
      Herein, four 5-LOX-derived lipids comprising 5-hydroxyeicosatetraenoic acid
      (HETE) attached to phospholipids (PLs), either phosphatidylethanolamine (PE) or
      phosphatidylcholine (18:0p/5-HETE-PE, 18:1p/5-HETE-PE, 16:0p/5-HETE-PE, and
      16:0a/5-HETE-PC), were identified in primary human neutrophils. They formed
      within 2 minutes in response to serum-opsonized Staphylococcus epidermidis or f
      methionine-leucine-phenylalanine, with priming by lipopolysaccharide, granulocyte
      macrophage colony-stimulating factor, or cytochalasin D. Levels generated were
      similar to free 5-HETE (0.37 +/- 0.14 ng vs 0.55 +/- 0.18 ng/10(6) cells,
      esterified vs free 5-HETE, respectively). They remained cell associated,
      localizing to nuclear and extranuclear membrane, and were formed by fast
      esterification of newly synthesized free 5-HETE. Generation also required Ca(2+),
      phospholipase C, cytosolic and secretory phospholipase A(2), 5-LOX activating
      protein, and mitogen-activated protein kinase/extracellular signal-regulated
      kinase kinase 1. 5-HETE-PLs were detected in murine S epidermidis peritonitis,
      paralleling neutrophil influx, and in effluent from Gram-positive human bacterial
      peritonitis. Formation of neutrophil extracellular traps was significantly
      enhanced by 5-LOX inhibition but attenuated by HETE-PE, whereas 5-HETE-PE
      enhanced superoxide and interleukin-8 generation. Thus, new molecular species of
      oxidized PL formed by human neutrophils during bacterial infection are identified
      and characterized.

PMID- 21177436
TI  - Prognostic impact, concurrent genetic mutations, and gene expression features of
      AML with CEBPA mutations in a cohort of 1182 cytogenetically normal AML patients:
      further evidence for CEBPA double mutant AML as a distinctive disease entity.
AB  - We evaluated concurrent gene mutations, clinical outcome, and gene expression
      signatures of CCAAT/enhancer binding protein alpha (CEBPA) double mutations
      (CEBPA(dm)) versus single mutations (CEBPA(sm)) in 1182 cytogenetically normal
      acute myeloid leukemia (AML) patients (16-60 years of age). We identified 151
      (12.8%) patients with CEBPA mutations (91 CEBPA(dm) and 60 CEBPA(sm)). The
      incidence of germline mutations was 7% (5 of 71), including 3 C-terminal
      mutations. CEBPA(dm) patients had a lower frequency of concurrent mutations than
      CEBPA(sm) patients (P < .0001). Both, groups were associated with a favorable
      outcome compared with CEBPA(wt) (5-year overall survival [OS] 63% and 56% vs 39%;
      P < .0001 and P = .05, respectively). However, in multivariable analysis only
      CEBPA(dm) was a prognostic factor for favorable OS outcome (hazard ratio [HR]
      0.36, P < .0001; event-free survival, HR 0.41, P < .0001; relapse-free survival,
      HR 0.55, P = .001). Outcome in CEBPA(sm) is dominated by concurrent NPM1 and/or
      FLT3 internal tandem duplication mutations. Unsupervised and supervised GEP
      analyses showed that CEBPA(dm) AML (n = 42), but not CEBPA(sm) AML (n = 18),
      expressed a unique gene signature. A 25-probe set prediction signature for
      CEBPA(dm) AML showed 100% sensitivity and specificity. Based on these findings,
      we propose that CEBPA(dm) should be clearly defined from CEBPA(sm) AML and
      considered as a separate entity in the classification of AML.

PMID- 21177437
TI  - Early visual experience of food does not appear to reduce subsequent feed
      neophobia in turkeys.
AB  - Turkeys may reduce their feed intake because of neophobia toward a new diet;
      however, their feeding behavior is not well known. The aim of this study was
      therefore to investigate the effects of diet color on behavior and feed intake in
      turkeys. For 2 wk, 2 groups of 1-day-old turkey chicks were fed diets varying in
      color but of the same composition: light-colored crumbles (LC group) or dark
      colored crumbles (DC group). Both groups (total n = 144) were then fed a novel
      diet of green crumbles for the next 2 wk. On d 30, the original groups were each
      divided into 3 groups and received light, dark, or green pellets. We postulated
      that neophobia on d 30 would be reduced for chicks fed 1) green pellets compared
      with diets of other colors because of the effect of recent experience, and 2) a
      diet of a color that was previously encountered over the first 2 wk of life.
      Behavior and feed intake were measured on the days before and during each feed
      transition at 5 min after the changeover feed to observe the short-term reaction.
      On the first transition day, birds in the LC group decreased their feed intake
      significantly at 5 min, unlike birds in the DC group, which increased their feed
      intake. Exploratory behavior increased in both groups when they received green
      crumbles on the transition day, indicating a response to the color. The
      changeover to pellets induced a reduction in feed intake in all groups at 5 min,
      but, in line with our first hypothesis, behavioral changes were less pronounced
      in birds receiving green pellets. However, turkeys in the DC group did not eat
      more dark-colored pellets than those in the other groups, and turkeys in the LC
      group did not eat more light-colored pellets. In the present experiment, we
      conclude that previous visual experience did not reduce subsequent feed neophobia
      but that color continuity facilitated a diet change from one feed form to
      another.

PMID- 21177435
TI  - HIF1alpha synergizes with glucocorticoids to promote BFU-E progenitor self
      renewal.
AB  - With the aim of finding small molecules that stimulate erythropoiesis earlier
      than erythropoietin and that enhance erythroid colony-forming unit (CFU-E)
      production, we studied the mechanism by which glucocorticoids increase CFU-E
      formation. Using erythroid burst-forming unit (BFU-E) and CFU-E progenitors
      purified by a new technique, we demonstrate that glucocorticoids stimulate the
      earliest (BFU-E) progenitors to undergo limited self-renewal, which increases
      formation of CFU-E cells > 20-fold. Interestingly, glucocorticoids induce
      expression of genes in BFU-E cells that contain promoter regions highly enriched
      for hypoxia-induced factor 1alpha (HIF1alpha) binding sites. This suggests
      activation of HIF1alpha may enhance or replace the effect of glucocorticoids on
      BFU-E self-renewal. Indeed, HIF1alpha activation by a prolyl hydroxylase
      inhibitor (PHI) synergizes with glucocorticoids and enhances production of CFU-Es
      170-fold. Because PHIs are able to increase erythroblast production at very low
      concentrations of glucocorticoids, PHI-induced stimulation of BFU-E progenitors
      thus represents a conceptually new therapeutic window for treating erythropoietin
      resistant anemia.

PMID- 21177438
TI  - Effect of heating and aging of poultry litter on the persistence of enteric
      bacteria.
AB  - Food-borne illnesses have rarely been associated with the reuse of poultry litter
      as an organic fertilizer and soil amendment in agriculture. Yet farming practices
      in many countries have come under increased scrutiny because of heightened
      consumer awareness of food safety and environmental issues. This study was
      conducted to determine whether simple on-farm management practices could improve
      the microbiological safety of poultry litter. First, the effects of heat and
      moisture on the survival of Escherichia coli and Salmonella enterica serovar
      Typhimurium in poultry litter were investigated under laboratory conditions.
      Second, the persistence and regrowth of enteric bacteria were examined in poultry
      litter that had been aged for up to 12 wk in either a turned or static (unturned)
      windrow. Escherichia coli and Salmonella counts in poultry litter were reduced by
      >99% in 1 h at 55 or 65 degrees C under laboratory conditions. At 35 degrees C,
      both persisted longer under moist (65% wt/wt, wet basis) than dry (30% wt/wt)
      conditions. Poultry litter aged for 3 wk in a turned windrow, and up to 6 wk in a
      static windrow, supported increased E. coli densities when incubated in the
      laboratory at 37 degrees C for 21 d. Peak temperatures >65 degrees C were
      observed in both windrows within the first 3 wk of aging; after this point, the
      turned windrow was more consistently exposed to temperatures >45 degrees C than
      the static windrow. By 12 wk, however, E. coli counts were very similar (3 to 3.6
      log(10)) in the outside edge of both windrows. This study highlights the need for
      a better understanding of the interrelationship between spontaneous heating in
      organic waste streams, organic matter stabilization, and pathogen reduction.

PMID- 21177439
TI  - The viability and performance under hot conditions of featherless broilers versus
      fully feathered broilers.
AB  - Hot conditions decrease the difference between ambient temperature (AT) and the
      average temperature of the body surface. A smaller difference reduces the rate of
      sensible heat loss of excessive internal heat, elevates the body temperature
      (BT), and may lead to mortality during heat waves. Under conditions of chronic
      heat, broilers avoid lethal BT elevation by reducing their feed intake;
      consequently, growth rate and meat yield are lower. Practices to avoid hot
      conditions are costly, whereas breeding for heat tolerance offers a sustainable
      approach. Being featherless was shown to provide heat tolerance; this was
      reevaluated in experimental broilers with a growth rate similar to that of
      contemporary commercial broilers. In experiment 1, 26 featherless birds and 49
      feathered siblings (sibs) were reared at warm AT and exposed to moderate and
      acute heat waves. The featherless birds maintained normal BT under a moderate
      heat wave, with a slight elevation under an acute heat wave, and only 1 bird
      died. In contrast, the heat waves led to a significant elevation in BT of the
      feathered sibs, and 34% of them died. In experiment 2, featherless broilers were
      compared with feathered sibs and commercial broilers at 2 AT treatments: a
      constant temperature of 25 degrees C (control AT) or a constant temperature of 35
      degrees C (hot AT). The birds were reared to 46 or 53 d at the control and hot
      AT, respectively, and the measured traits included BT, growth, and weight of the
      whole body and carcass parts (breast meat, legs, wings, and skin). At the hot AT,
      only the featherless broilers maintained a normal BT; their mean d 46 BW (2,031g)
      was significantly higher than that of birds maintained at the control AT, and it
      increased to 2,400 g on d 53, much higher than the corresponding means of all
      feathered broilers (approximately 1,700 g only). Featherless broilers had
      significantly higher breast meat yield (approximately 20% in both AT), lower skin
      weight, and supposedly better wing quality. These results confirmed that being
      featherless improved the livability and performance of fast-growing broilers in
      hot conditions and suggests that introduction of the featherless phenotype into
      commercial broiler stocks would facilitate highly efficient yet low-cost
      production of broiler meat under hot conditions.

PMID- 21177440
TI  - Evaluation of egg production in layers using random regression models.
AB  - The objectives of this study were to estimate genetic parameters for egg
      production over the age trajectory in 3 layer lines, which represent different
      biotypes for egg production, and to validate the use of breeding values for slope
      as a measure of persistency to be used in the selection program. Egg production
      of more than 26,000 layers per line from 6 consecutive generations were analyzed
      with a random regression model with a within-hatch-nested fifth-order fixed
      regression polynomial and linear polynomials for random additive genetic and
      permanent environmental effects. Daily records were cumulated into biweekly
      periods. In all lines, a nonzero genetic variance for mean and slope and a
      positive genetic correlation between mean and slope were estimated. Genetic
      variance of egg production by 2-wk period was low at the beginning of lay and
      increased as the birds aged for all 3 lines, which resulted in heritability
      estimates increasing with age. Breeding values for slope reflected the shape of
      the egg production curve well and can be used to directly select for persistency
      of egg production.

PMID- 21177441
TI  - Ornithine decarboxylase gene is a positional candidate gene affecting growth and
      carcass traits in F2 intercross chickens.
AB  - The ornithine decarboxylase (ODC) gene is a candidate gene for growth and carcass
      traits. It is located on chicken chromosome 3 in a region where QTL for growth
      and carcass traits have previously been detected in the F2 population. The
      objectives of this study were to identify polymorphisms of the ODC gene in an F2
      resource population and to examine the effects of these ODC polymorphisms on
      growth and carcass traits. The F2 resource population was obtained by crossing a
      Shamo male and White Plymouth Rock females. The F2 population was then measured
      for growth and carcass traits and used for positional candidate gene analysis. A
      total of 6 novel SNP and a novel indel mutation were identified in the parental
      population. Three SNP (g.-638A>G, g.-465C>T, and g.-353C>T) and a 4-bp indel
      mutation (g.-633_-632ins) in the promoter region of the ODC gene were identified
      in the parental population, and 2 haplotypes composed of these mutations were
      segregated in the parental population. A QTL analysis was performed, and the QTL
      for some growth and carcass traits were detected at a significant level and on a
      similar position to the ODC gene. Significant associations were found between
      haplotypes in the promoter region of the ODC gene and these traits in the F2
      population, and the effect of haplotype on BW at 9 wk of age was the most
      significant. The haplotypes of the ODC gene found in this study might help in
      understanding the genetic structure of growth and carcass traits and in improving
      these traits directly by MAS. Therefore, further functional studies are necessary
      to evaluate the effects of promoter mutations at a molecular level.

PMID- 21177442
TI  - Genetic parameters for feed utilization traits in Japanese quail.
AB  - Feed costs substantially affect the efficiency of poultry operations, justifying
      genetic improvement of feed utilization by selection. The current research was
      conducted to estimate genetic variance for the 4-wk feed conversion ratio (FCR)
      and its genetic correlations with BW, BW gain (WG), feed intake (FI), and
      residual feed intake (RFI) in Japanese quail. The data analyzed originated from a
      line selected for low FCR for 3 generations. In each generation, 35 sires and 70
      dams were used as parents for the next generation. Body weight and WG were
      recorded on a total of 1,226 individuals, whereas FCR, RFI, and FI were recorded
      on 505 family groups. The results showed that heritability estimates (+/-SE) of
      BW at 28 d of age and WG between 7 and 28 d of age were 0.22 +/- 0.05 and 0.28 +/
      0.06, respectively. For FI, FCR, and RFI, significant genetic variances were
      estimated. Genetic correlations of FCR between 7 and 28 d of age with WG and FI
      between 7 and 28 d of age were -0.45 +/- 0.09 and 0.24 +/- 0.08, respectively.
      This implies that a low FCR is genetically related to a high WG and low FI. The
      genetic correlation between FCR from 7 to 28 d of age and RFI from 7 to 28 d of
      age was 0.26 +/- 0.08, indicating that the 2 alternative feed efficiency traits
      are genetically different traits, and that the correlated genetic response in one
      of them in response to selection on the other is likely to be only moderate.
      Genetic correlations of RFI from 7 to 28 d of age with WG and FI between 7 and 28
      d of age were 0.08 +/- 0.04 and 0.74 +/- 0.11, respectively. This reflects the
      fact that RFI is phenotypically independent of WG, which tends to make the
      genetic correlation between RFI and WG low as well. In conclusion, all the traits
      analyzed displayed significant genetic variance, allowing their genetic
      improvement by selection, yet the alternative feed utilization traits, FCR and
      RFI, displayed different genetic characteristics.

PMID- 21177443
TI  - Effect of low levels of aflatoxin B1 on performance, biochemical parameters, and
      aflatoxin B1 in broiler liver tissues in the presence of monensin and sodium
      bentonite.
AB  - Aflatoxins (AF) are a major problem in broiler production and are significant
      economic and public health burdens worldwide. A commercial sodium bentonite (Na
      B) adsorbent was used to prevent the effect of AF [50 ug of aflatoxin B1
      (AFB1)/kg of feed] in broiler productivity, biochemical parameters, macroscopic
      and microscopic liver changes, and AFB1 liver residues. The influence of Na-B
      (0.3%) and monensin (MON, 100 mg/kg), alone or in combination, was investigated
      in depth. The dietary treatments were as follows: treatment (T) 1: basal diet
      (B); T2: B + MON; T3: B + Na-B; T4: B + Na-B + MON; T5: B + AFB1; T6: B + AFB1 +
      Na-B + MON; T7: B + AFB1 + MON; T8: B + AFB1 + Na-B. Birds were fed dietary
      treatments for 28 d (d 18 to 46). No significant differences (P < 0.05) were
      observed among treatments with respect to broiler performance, biochemical
      parameters, or relative liver weights. With the exception of T8, all livers
      showed histopathological alterations, with accumulation of fat vacuoles. The
      normal appearance of livers from T8 showed the protective effect of Na-B against
      aflatoxicosis. The residual AFB1 levels in livers from T5 to T8 ranged from 0.2
      to 1.0 ng/g and were higher in livers from T6 (P < 0.05). Results of this study
      indicate a competition between AFB1 and MON for adsorption sites on Na-B when
      feed contains low levels of the toxin, indicating a nonselective adsorption
      capacity of this particular Na-B. In addition, significant levels of AFB1 in
      livers indicate that this determination is an important technique not only for
      diagnosis of aflatoxicosis in broilers, but also for quality control of avian
      products.

PMID- 21177444
TI  - Salmonella Typhimurium oral challenge model in mature broilers: bacteriological,
      immunological, and growth performance aspects.
AB  - In this study, Salmonella enterica serovar Typhimurium challenge models were
      tested to identify the best conditions under which to perform the experimental
      infection of 3-wk-old broilers. Such a model would be useful to study the
      efficiency of therapeutic treatments that could take place at the end of the grow
      out period. Salmonella-free chicks were obtained from a breeder flock vaccinated
      with Salmonella. Intestinal maternal immunity was monitored by ELISA analyses at
      2, 9, and 16 d of age. Data indicated that protection of maternal origin was not
      maintained over time and was drastically reduced at 9 d of age (P < 0.01). At 21
      d of age, chickens were orally inoculated with Salmonella Typhimurium. The
      effects of the oral challenge dose (0, 3 * 10(3), 3 * 10(6), and 3 * 10(9)
      cfu/bird) and vancomycin pretreatment (no administration or 25 mg/bird) on
      intestinal immune responses, growth performance, and Salmonella colonization of
      chickens were investigated. After infection, the mucosal immune response was
      rapid, with increased (P < 0.01) anti-Salmonella Typhimurium IgA titers measured
      at 8 d postinfection in intestinal contents. A linear relationship (P < 0.05)
      existed between specific IgA levels in intestinal and cecal contents and the
      challenge dose inoculated. None of the challenge protocols caused mortality or
      clinical symptoms after infection. Nevertheless, the experimental infection
      induced a significant deterioration of growth performance. The pretreatment with
      25 mg of vancomycin at 3 h before Salmonella inoculation was able to establish
      stable infection rates among the population of 3-wk-old infected chickens.
      Nevertheless, Salmonella shedding was not stable over the rearing period, and the
      bacteria seemed to be naturally eliminated from most birds at 22 d postinfection.
      This natural clearance of the gut, which was related, at least in part, to the
      intestinal immune response, should limit the usability of the created mature
      challenge model within 1 to 2 wk after inoculation.

PMID- 21177445
TI  - Changes in chemical composition in male turkeys during growth.
AB  - In growing animals, requirements for many nutrients (and energy) are determined
      by the retention of these nutrients. During growth, this retention changes in an
      absolute way and also between nutrients and energy, resulting in changing
      nutrient requirements. The objective of this study was to describe the changes in
      chemical composition in male growing turkeys. The serial slaughter technique was
      used to determine the composition of amino acids, lipid, ash, and water in
      feather-free body (FFB) and feathers in male turkeys offered feed ad libitum from
      1 to 15 wk of age. Allometric relations were used to describe changes in body
      composition. The feather content in the body decreased from 6% at 1 wk of age to
      less than 3% at 15 wk of age. The water and protein content in FFB decreased with
      increasing FFB mass, with allometric scalars (b) of, respectively, 0.967 and
      0.970, whereas the lipid content increased with increasing FFB mass (b = 1.388).
      The water, protein, and ash content in fat-free FFB was constant and represented,
      respectively, 71.6, 24.2, and 4.2% of the fat-free FFB mass. The amino acid
      content of FFB protein was relatively constant and only the Cys content decreased
      between 1 and 15 wk of age, whereas the Ile content increased. Feathers were
      mostly composed of protein, and the protein content did not change during growth.
      During growth, the Lys, Met, Trp, His, Tyr, Asp, and Glu contents in feather
      protein decreased, whereas the Cys, Val, and Ser contents increased. The
      contribution of feathers to whole-body amino acid retention ranged from 5% for
      His to 33% for Cys. On average, the weight gain of FFB contained 21.3% protein
      and 12.7% lipid, corresponding to an energy content of 10.1 kJ/g. The weight gain
      of feathers contained 87.4% protein, corresponding to an energy content of 20.4
      kJ/g. The results of the present study can be used in a factorial approach to
      determine nutrient requirements in growing turkeys.

PMID- 21177446
TI  - Effect of dietary prebiotic supplementation on the performance, intestinal
      microflora, and immune response of broilers.
AB  - This study investigated the effects of dietary supplementation with the
      prebiotics fructo-oligosaccharide (FOS) and mannan-oligosaccharide (MOS) on the
      performance, small intestinal microflora, and immune response of broilers. Two
      hundred forty 1-d-old Ross broiler chickens were randomly assigned to 6 dietary
      treatment groups: control, avilamycin (6 mg/kg), 0.25% FOS, 0.5% FOS, 0.025% MOS,
      and 0.05% MOS. Each treatment was fed to 4 replicates of 10 birds per diet for 4
      wk. Except for the 0.5% FOS group, the overall BW gains of birds treated with
      avilamycin and prebiotics were significantly(P < 0.05) higher than those of the
      control group. No significant differences were found between the control and
      supplemented groups in overall feed intake, feed conversion, and mortality. The
      0.05% MOS group was significantly (P < 0.05) lower than the control and 0.5% FOS
      groups in heterophil:lymphocyte ratio and basophil level. Concentrations of
      plasma IgA and IgG were not significantly different among the treatment groups.
      Quantitative real-time PCR indicated that supplementation of the diet with
      avilamycin or prebiotics caused significant (P < 0.05) changes in the small
      intestinal microbial community, as determined in samples obtained at the
      ileocecal junction. The populations of Clostridium perfringens and Escherichia
      coli decreased with 0.25% FOS, 0.05% MOS, or avilamycin, and lactobacilli
      increased in the 0.25% FOS and 0.25% MOS treatment groups. Total bacteria
      increased in the 0.25% FOS and 0.05% MOS treatments and decreased in the
      avilamycin treatment. Feeding 0.25% FOS and 0.05% MOS resulted in an increase in
      lactobacillus community diversity in the ileum. Our results showed that 0.25% FOS
      and 0.05% MOS were comparable with avilamycin in improving productivity in
      broilers raised in wire floor cages up to 28 d of age. Plasma immunoglobulins
      were not affected by prebiotics, but the heterophil:lymphocyte ratio, basophil
      level, and microbial population in the ileum were significantly affected.

PMID- 21177447
TI  - Functional characterization of folic acid transport in the intestine of the
      laying hen using the everted intestinal sac model.
AB  - Absorption at the level of the intestine is likely a primary regulatory mechanism
      for the deposition of dietary supplemented folic acid into the chicken egg.
      Therefore, factors affecting the intestinal transport of folic acid in the laying
      hen may influence the level of egg folate concentrations. To this end, a series
      of experiments using intestinal everted sacs were conducted to characterize
      intestinal folic acid absorption processes in laying hens. Effects of naturally
      occurring folate derivatives (5-methyl and 10-formyltetrahydrofolate) as well as
      heme on folic acid absorption were also investigated. Folic acid absorption was
      measured based on the rate of uptake of (3)H-labeled folic acid in the everted
      sac from various segments of the small and large intestines. Folic acid
      concentration, incubation length, and pH condition were optimized before the
      performance of uptake experiments. The distribution profile of folic acid
      transport along the intestine was highest in the upper half of the small
      intestine. Maximum uptake rate (nmol.100 g tissue(-1).min(-1)) was observed in
      the duodenum (20.6 +/- 1.9) and jejunum (22.3 +/- 2.0) and decreased
      significantly in the ileum (15.3 +/- 1.1) and cecum (9.3 +/- 0.9). Transport
      increased proportionately (P < 0.05) between 0.0001 and 0.1 uM folic acid. Above
      0.1 uM, the slope of the regression line was not significantly different from
      zero (P < 0.137). Folic acid uptake in the jejunum showed a maximum rate of
      transport at pH 6.0, but was lowest at pH 7.5. The presence of 5-methyl and 10
      formyltetrahydrofolate as well as heme impeded folic acid uptake, reducing
      intestinal folic acid absorption when added at concentrations ranging from 0 to
      100 uM. Overall, these data indicated the presence of a folic acid transport
      system in the entire intestine of the laying hen. Uptake of folic acid in the
      cecum raises the likelihood of absorption of bacterial-derived folate.

PMID- 21177448
TI  - Effects of dietary enzymes on performance and intestinal goblet cell number of
      broilers exposed to a live coccidia oocyst vaccine.
AB  - An experiment was conducted to evaluate the effects of dietary enzymes on
      performance, tibia ash, and intestinal goblet cells of broilers administered a
      live coccidia oocyst vaccine (Coccivac B, Schering Plough, Kenilworth, NJ). Cobb
      500 straight-run broilers were obtained and one-half of the chicks were sprayed
      with the live coccidia oocyst vaccine. Chicks were weighed and placed in battery
      brooders with respect to nonvaccinated or vaccinated group according to dietary
      treatment. The 8 dietary treatments were a positive control (0.90% Ca and 0.45%
      available P), a negative control (NC; 0.80% Ca and 0.35% available P), NC +
      phytase (PHY), NC + protease (PRO), NC + xylanase (XYL), NC + PHY+ PRO, NC + PHY
      + XYL, and NC + PHY + PRO + XYL. A diet * vaccination interaction (P > 0.05) was
      not observed for feed intake or BW gain. Feed conversion ratio was improved (P <=
      0.05) in birds fed NC + PHY + XYL compared with NC. Vaccination reduced (P <=
      0.05) feed intake and BW gain from d 0 to 18. Tibia ash was reduced (P <= 0.05)
      in the NC and PRO or XYL diets. Vaccination increased goblet cell numbers in the
      duodenum of birds fed XYL, whereas no differences were found in goblet cell
      numbers between nonvaccinated and vaccinated birds in other dietary treatments,
      which resulted in a diet * vaccination interaction (P <= 0.05). Protease
      decreased and NC + PHY+ PRO increased goblet cells in the jejunum at d 7, which
      resulted in a diet * vaccination interaction (P <= 0.05). At d 18, NC + PHY + XYL
      was the only diet in which vaccination decreased goblet cells in the jejunum,
      resulting in a diet * vaccination interaction (P <= 0.05). The data indicate that
      NC + PHY + XYL improved the feed conversion ratio in broilers fed corn-soybean
      meal diets. The vaccination * dietary enzyme interaction altered the number of
      goblet cells in the small intestine. Dietary enzyme supplementation did not
      alleviate reductions in growth performance associated with the use of a live
      coccidia oocyst vaccine.

PMID- 21177449
TI  - Dietary protein effects on hen performance and nitrogen excretion.
AB  - Because dietary nitrogen intake affects nitrogen content in manure, diet
      management has been recognized as a means to reduce ammonia emissions from
      poultry operations. The objectives of the present research were 1) to determine
      the extent to which the CP content of laying diets can be reduced, based on
      performance criteria, and 2) to determine how ash:nitrogen ratios of manure,
      eggs, and hens are affected by dietary protein changes. Egg-type hens were fed
      equal daily amounts of essential amino acids in diets that provided 13, 15, or 17
      g of protein/d. Each diet was fed to 20 hens, with 2 hens/cage. The planned
      digestible lysine intake was 0.71 g/hen per day. Ratios of other digestible amino
      acids to lysine were methionine plus cysteine, 0.83; threonine, 0.68; and
      isoleucine, 0.94. The experiment began when hens were 29 wk old and continued
      until they were 57 wk old. Egg production averaged approximately 90%, and daily
      protein intake caused no effects on egg production or grams of egg per hen per
      day. Feed intake was higher for hens fed 13 g of protein than for hens in the
      other 2 treatments (P < 0.01). Average feed intake for the experiment was
      approximately 95 g/d. Composition of the eggs was not affected by protein intake.
      Average values were DM, 30.5%; ash, 31.0% of DM; and nitrogen, 6.31% of DM. The
      average manure DM production was 25.9 g/hen per day, with an ash content of 25.5%
      of DM. Manure nitrogen content ranged from 3.98% of DM for hens fed 13 g of
      protein to 5.68% for those fed 17 g of protein (P < 0.01). A method is outlined
      that uses the analysis of fresh manure and manure leaving the poultry operation
      to estimate the loss of nitrogen as ammonia.

PMID- 21177450
TI  - Gene expression profile in the liver tissue of geese after overfeeding.
AB  - Geese form a fatty liver after feeding on a carbohydrate-rich diet, possibly as
      an evolutionary adaptation to accumulate reserves for migration. To gain insight
      into the gene-regulation processes of hepatic steatosis in geese, we examined the
      profile of transcriptional expression in goose fatty liver and control liver by
      suppression subtractive hybridization and measured the levels of serum
      biochemical variables. We found 107 genes whose expression was different between
      the treatment and control groups. The main functions of these genes are metabolic
      processes, including the metabolism of carbohydrates, amino acids, and lipids.
      Twenty-four genes were classified using the Kyoto Encyclopaedia of Genes and
      Genomes pathways. Twelve genes that related to metabolic and cellular processes
      were confirmed by quantitative RT-PCR. A specific positive effect of feeding was
      observed on the expression of genes involved mainly in unsaturated fatty acids
      and triglyceride synthesis, and a negative effect was observed on genes involved
      in beta-oxidation, cholesterol metabolism, and glycolysis. The results could
      serve as an important reference for the development of goose breeding for fatty
      liver production and human liver disease research.

PMID- 21177451
TI  - Effect of incubation temperature on nutrient transporters and small intestine
      morphology of broiler chickens.
AB  - This study evaluated the effects of elevated incubation temperature on posthatch
      nutrient transporter gene expression, integrity of the intestinal epithelium,
      organ development, and performance in Ross 308 broiler chickens. Ross * Ross 308
      fertile eggs (n = 900) were incubated at different eggshell temperatures during
      development. From embryonic day (ED) 1 to ED12, all eggs were incubated at 37.1
      degrees C, whereas from ED13 to ED21, the eggs were divided into 2 groups for
      incubation at 37.4 degrees C (S) or 39.6 degrees C (H). Performance
      characteristics were measured at day of hatch (DOH) and d 7, 14, 21, 30, and 42.
      Small intestine and residual yolk sacs were collected at DOH and d 2, 4, 6, and
      10 and weighed individually. Intestinal samples from the duodenum, jejunum, and
      ileum were evaluated for mucosal morphology and relative nutrient transporter
      gene expression. No significant differences were found in performance or organ
      weights. The intestinal morphology results showed a temperature * age interaction
      in duodenum villus height (P = 0.02) and crypt depth (P = 0.05) and in ileum
      villus height-to-crypt depth ratios (P = 0.02). There was a main effect of
      temperature, resulting in deeper crypts (P = 0.02) in the jejunum of chicks
      incubated at H compared with S. In the nutrient gene expression evaluation,
      peptide transporter (PepT1) showed a temperature * age interaction. On DOH and d
      2, 4, and 10, PepT1 expression was similar between chicks incubated at S and H.
      However, on d 6, chicks incubated at S had significantly higher expression of
      PepT1 than those incubated at H. This study presents the effects of elevated
      incubation temperature on small intestine morphology and relative expression of
      nutrient transporter mRNA in high-yield broiler chicks, which can be important
      for the availability of nutrients and distribution of energy.

PMID- 21177452
TI  - Sensitivity of organ growth to chronically low oxygen levels during incubation in
      Red Junglefowl and domesticated chicken breeds.
AB  - Genetic selection programs have imposed large phenotypic changes in domesticated
      chicken breeds that are also apparent during embryonic development. Broilers, for
      example, have a faster growth rate before hatching in comparison with White
      Leghorns, indicating that the allocation of resources toward different functions
      already begins before hatching. Therefore, we hypothesized that embryonic organ
      growth would follow different developmental trajectories and would be
      differentially affected by an oxygen shortage during incubation. Heart, brain,
      and liver growth were studied in broiler, White Leghorn, and Red Junglefowl
      embryos at embryonic (E) ages E11, E13, E15, E18, and E20, and the results were
      fitted to growth allometric equations to determine the degree of organ stunting
      or sparing caused by low oxygen during incubation. Hypoxia caused a 3-fold larger
      mortality in Red Junglefowl than in the domesticated breeds, with a similar
      impairment of embryonic growth of 18%, coupled with a reduction in yolk
      utilization of 56%. Relative brain size was not affected by hypoxia in any breed,
      but a substantial stunting effect was observed for the liver and heart at late
      embryonic ages, with marked differences between breeds. In Red Junglefowl, only
      the heart was stunted. In White Leghorns, only the liver was stunted, and in
      broilers, both organs were stunted. These results can be explained in terms of
      the selection pressure on long-term production traits (reproductive effort) in
      White Leghorns, requiring a more efficient lipid metabolism, compared with the
      selection pressure on shorter-term production traits (growth) in broilers,
      requiring overall metabolic turnover and convective nutrient delivery to all
      tissues. At the same time, a remarkable sparing of the heart was observed in
      broilers and Red Junglefowl between E11 and E15, which suggests that cardiac
      growth can be manipulated during embryonic development. This result could be
      relevant for manipulating the phenotype of the heart for management purposes at a
      developmental stage when the bird is most versatile and phenotypically malleable.

PMID- 21177453
TI  - A comparative transcriptomic study of vitamin E and an algae-based antioxidant as
      antioxidative agents: investigation of replacing vitamin E with the algae-based
      antioxidant in broiler diets.
AB  - Previous study indicated that inclusion of an algae-based antioxidant as an
      antioxidative agent [EconomasE, Alltech, Nicholasville, KY; EcoE] significantly
      reduced the amount of vitamin E (VE) required in broiler diets without
      compromising performance and meat quality. To assess the mechanisms related to
      the VE-saving activity of EcoE, as well as other potential functions related to
      EcoE and VE supplementation, we analyzed gene expression profiles of breast
      muscle from broilers fed a control diet, the control diet + 50 IU of VE/kg, the
      control diet + 100 IU of VE/kg, or the control diet + 200 g of EcoE/ton.
      Evaluation of the serum antioxidant capacity indicated that dietary
      supplementation of either a high level of VE (50 or 100 IU of VE/kg) or EcoE
      significantly improved bird antioxidant status. Analysis of gene expression
      profiles indicated that expression of 542 genes of the breast muscle were altered
      (P < 0.05, fold change >1.2) by dietary treatments, of which a significant part
      were commonly regulated by EcoE and VE (especially the control diet + 50 IU of
      VE/kg). In addition to the process of cellular oxidation, gene ontology analysis
      indicated the involvement of EcoE and VE on cell morphology, skeletal and
      muscular system development and function, immune response, and multiple metabolic
      processes, including lipid, carbohydrate, and drug metabolism. Results of this
      experiment indicate that the biological roles of high VE, including its activity
      as an antioxidant, can be greatly mimicked at the transcriptional level by EcoE,
      and they suggest a relationship of functional redundancy between VE and EcoE in
      the broiler diets.

PMID- 21177454
TI  - Effects of flaxseed, sardines, pearl millet, and holy basil leaves on production
      traits of layers and fatty acid composition of egg yolks.
AB  - The effects of flaxseed, sardines, pearl millet, and holy basil (Oscimum sanctum)
      leaf meal on Single Comb White Leghorn (Forsgate strain) layer hen production
      traits, fatty acid composition of egg yolks, and egg quality characteristics were
      studied. Layer hens were allocated to 1 of 6 dietary treatments from 27 to 32 wk
      of age: control (treatment 1), control + 1 g of basil leaf meal (BLM) (treatment
      2), control + 2 g of BLM (treatment 3), designer egg layer mash (DELM; treatment
      4), DELM + 1 g of BLM (treatment 5), DELM + 2 g of BLM (treatment 6). No
      significant differences were found in egg production between dietary treatments,
      indicating that neither the designer diet nor the BLM had an adverse effect on
      egg production. The high energy level in the designer diet, because of the
      flaxseed oil and sardines, significantly reduced feed intake compared with the
      control diet. The egg weight was significantly higher in birds fed the designer
      diet compared with the egg weight in the control diet. The flaxseed oil and
      sardine oil, which are rich in n-3 polyunsaturated fatty acids, contributed to
      significantly increased n-3 polyunsaturated fatty acid levels in the egg yolks,
      with a proportionate reduction in the level of palmitic acid. Other fatty acids
      showed only minor variations. Flaxseed oil increased the level of alpha-linolenic
      acid, whereas fish oil increased the eicosapentaenoic acid and docosahexaenoic
      acid levels. The BLM at low levels of inclusion (1 and 2 g/kg) also contributed
      significantly to elevating the yolk n-3 polyunsaturated fatty acid levels,
      especially C18:3. Holy basil leaf meal is a good feed supplement for increasing
      the yolk alpha-linolenic acid level by reducing the yolk saturated fatty acid
      levels proportionately.

PMID- 21177455
TI  - The effects of water replacement by oral rehydration fluids with or without
      betaine supplementation on performance, acid-base balance, and water retention of
      heat-stressed broiler chickens.
AB  - Exposing broilers to a high temperature increases water and electrolyte K(+) and
      Na(+) excretion, which negatively affects the heat dissipation capacity and acid
      base homeostasis, resulting in losses in growth performance. In this experiment,
      the efficacy of providing oral rehydration therapy and betaine on growth
      performance, acid-base balance, and water and electrolyte retention was
      evaluated. A total of 432 one-day-old broiler chicks (Cobb) were allocated to 72
      metabolic cages and reared to 31 d of age under standard conditions. From 32 to
      41 d of age, chicks were exposed to heat stress (ambient temperature, 32 degrees
      C) and high RH (80 to 100% RH) for 9 h daily. The ameliorative effects of a 3 * 3
      factorial array of treatments administered via drinking water were evaluated in 8
      replicates of 6 chicks per cage for each treatment. Two oral rehydration therapy
      (ORT) fluids, based on either citrate or bicarbonate salts, were added to tap
      water. In addition, betaine was added to tap water at an inclusion rate of 0,
      500, or 1,000 mg/L to complete the array of 9 liquid-based treatments. Growth
      performance was assessed at 32, 35, and 41 d of age. From 32 to 35 d of age,
      chicks receiving ORT fluids exhibited improved growth performance, water balance,
      and electrolyte (K(+), Na(+)) retention. In addition, the physiological response
      to stress was attenuated, as indicated by lower heterophil-to-lymphocyte ratios
      and blood glucose concentrations relative to the negative controls. The addition
      of betaine at an inclusion rate of 500 mg/L improved BW gain. From d 36 to 41,
      treatments did not significantly influence growth performance, which suggests
      that chicks receiving tap water were able to compensate and adapt to the heat
      stress conditions. The results demonstrate that the beneficial effects of
      providing ORT fluids and 500 mg of betaine/L were observed only during the first
      4 d of heat exposure. After this period, adaptation to the heat appears to occur,
      and none of the treatments was successful in improving growth performance.

PMID- 21177456
TI  - Applicability of lectin histochemistry in a test system with in ovo treatment for
      detecting androgenic and antiandrogenic effects of chemicals in Japanese quail
      (Coturnix japonica).
AB  - The aim of the current study was to examine whether analysis of the appearance of
      specific lectin-positive substances in the quail embryonic cloacal gland would be
      useful for evaluating the androgenic and antiandrogenic effects of chemicals.
      Fertilized Japanese quail eggs were injected with 0 to 75 ug of cyproterone
      acetate (CA), an antiandrogenic compound, on d 12 of incubation (d 12), followed
      by injection of 0 to 300 ug of testosterone propionate (TP) on d 13. Experimental
      groups consisted of a control group (corn oil injections on d 12 and 13), a TP-L
      group [corn oil and a low dose (L; 30 ug) of TP], a TP-H group [corn oil and a
      high dose (H; 300 ug) of TP], a CA-L + TP-H group [a low dose (L;7.5 ug) of CA +
      TP-H], and a CA-H + TP-H group [a high dose (H; 75 ug) of CA + TP-H]. The cloacal
      tissues were collected on d 16, processed into paraffin sections, and stained
      using 14 different biotinylated lectins. The Vicia villosa (VVA) lectin most
      strongly stained the developing cloacal glandular cells in TP-H. Western blotting
      analysis showed 1 VVA-positive band of approximately 75 kDa. The ratio of VVA
      positive areas per unit square examined microscopically by image analysis was
      significantly greater in the TP-H group than in the control group in both males
      and females. The ratio was significantly decreased in the CA-L + TP-H and CA-H +
      TP-H groups compared with the TP-H group in both males and females. Furthermore,
      the ratio was smaller in females than in males within a TP-L or TP-H treatment
      group. These results suggest that lectin histochemistry on quail embryonic cloaca
      using VVA is useful for evaluating the androgenic and antiandrogenic effects of
      chemical compounds.

PMID- 21177457
TI  - Parathyroid hormone-related peptide directly increases adrenocorticotropic
      hormone secretion from the anterior pituitary in hens.
AB  - The presence of the receptor for parathyroid hormone-related peptide (PTHrP) and
      the effect of PTHrP on adrenocorticotropic hormone (ACTH) secretion in the hen
      anterior pituitary were examined. The plasma membrane fraction of the anterior
      pituitary was found to contain a specific chicken PTHrP (cPTHrP) binding
      component. The binding component had properties of a receptor, such as binding
      specificity to cPTHrP, reversibility, saturable binding, high affinity, and
      limited capacity; therefore, it was elucidated that the PTHrP receptor exists in
      the plasma membrane of the hen anterior pituitary. A third ventricular injection
      of cPTHrP in nonlaying hens caused a decrease in the chicken ACTH level of the
      anterior pituitary and an increase in the chicken ACTH level of blood plasma,
      with an increase in the binding affinity and a decrease in the binding capacity
      of PTHrP receptor in the anterior pituitary. The present study suggests that
      PTHrP may act directly on the anterior pituitary via its receptor binding and may
      enhance ACTH secretion from this tissue in hens.

PMID- 21177458
TI  - Effect of organic and inorganic forms of selenium in diets on turkey semen
      quality.
AB  - The effects of Se supplementation and its organic or inorganic form on semen
      quantitative parameters (ejaculate volume, sperm concentration, and total number
      of sperm) and biochemical parameters of seminal plasma (protein concentration,
      acid phosphatase activity, superoxide dismutase activity, and total antioxidant
      capacity) were investigated over a 25-wk reproductive season. Additionally, DNA
      fragmentation and motility characteristics of turkey spermatozoa were measured.
      The parameters of turkey semen in relation to yellow semen syndrome were also
      determined. Twenty-four males (Big 6) were divided into 3 experimental groups
      differing in form of Se supplementation (no Se supplementation, 0.3 mg/kg of
      inorganic Se from sodium selenite and 0.3 mg/kg of organic Se from Sel-Plex,
      Alltech Inc., Nicholasville, KY). Dietary Se supplementation enhanced the sperm
      concentration and total number of sperm and did not influence the antioxidative
      properties of turkey seminal plasma and most biochemical parameters. Only seminal
      plasma acid phosphatase activity was increased in turkeys fed inorganic Se. The
      main sperm DNA fragmentation parameters were not affected by dietary Se. The
      highest percentage of motile spermatozoa (85%) was recorded for the semen of
      turkeys fed organic Se. Values of the biochemical parameters (acid phosphatase,
      superoxide dismutase, total antioxidant capacity) of seminal plasma increased
      during the reproductive season. Yellow semen was characterized by increased
      biochemical parameters and decreased spermatozoa motility characteristics.
      However, the percentage of motile spermatozoa did not differ between white and
      yellow semen. Organic Se seemed to be the preferred form of diet supplementation
      in comparison with inorganic Se. Biochemical parameters of semen and spermatozoa
      motility parameters appear to be useful for evaluating the effect of age on semen
      quality. Monitoring the DNA fragmentation of spermatozoa at the end of the
      reproductive season could be a useful tool for monitoring turkey semen quality.
      Increased superoxide dismutase activity can be used as an indicator of yellow
      semen. A decline in the quality of yellow semen can be related to a decrease in
      the spermatozoa motility parameters of turkeys.

PMID- 21177459
TI  - Effect of estradiol-17beta on calcitonin receptor bindings in the hen
      neurohypophysis.
AB  - The present study was performed to elucidate whether estradiol-17beta (E2) would
      affect calcitonin (CT) receptor binding in the hen neurohypophysis. The
      equilibrium dissociation constant (K(d)) and the maximum binding capacity
      (B(max)) of the CT receptor in the plasma membrane fraction of the hen
      neurohypophysis were examined by Scatchard analysis of specific binding of (125)I
      labeled chicken CT. A single i.m. injection of E2 into nonlaying hens caused a
      decrease in K(d) and B(max) values of the CT receptor. The K(d) and B(max) values
      of the CT receptor were smaller in laying hens than in nonlaying hens. The
      present study suggests that E2 may increase the action of CT on the
      neurohypophysis in hens.

PMID- 21177460
TI  - Performance optimization of soy and whey protein isolates as coating materials on
      chicken meat.
AB  - To determine the optimal coating performance of soy protein isolate (SPI) and
      whey protein isolate (WPI) on chicken meat, the effects of SPI (0 to 10%), WPI (0
      to 10%), and pH (3 to 8) on coating pickup, frying loss, yield, moisture, and fat
      content of chicken meat were investigated by response surface methodology.
      Chicken breast meat samples were dipped in protein solutions with different pH
      and then drained. Subsequently, they were coated with a dry commercial coating
      mixture, and the coated samples were deep-fat fried in margarine. Soy protein
      isolate had better performance on chicken meat than WPI. The performance
      increased significantly at higher pH values. Optimal responses were the minimum
      for coating pickup, yield, and moisture content and the maximum for frying loss
      and fat content. Critical values for the optimal responses were between 5.05 and
      5.80 pH, 2.74 and 4.65% SPI, and 3.10 and 4.74% WPI, respectively. However, the
      optimal breading performance combination was 7.13 pH, 9.0% SPI, and 0.6% WPI.

PMID- 21177461
TI  - Oxidative stability and sensory quality of meat from broiler chickens fed a
      bacterial meal produced on natural gas.
AB  - Bacterial meal (BPM) produced from bacteria grown on natural gas is a feed source
      containing approximately 70% CP and 10% lipids with predominantly C16:0 and C16:1
      fatty acids. The effect of increasing dietary levels (0, 40, 80, or 120 g/kg) of
      BPM on fatty acid composition, the profile of volatiles by dynamic headspace gas
      chromatography-mass spectrometry, and sensory quality of frozen-stored broiler
      chicken thigh meat was examined. Increasing levels of BPM increased (linear, P <
      0.0001) the content of saturated fatty acids, tended (linear, P = 0.05) to
      increase the content of monounsaturated fatty acids, and tended (linear, P =
      0.08) to decrease the content of polyunsaturated fatty acids in the meat. Feeding
      BPM reduced (linear, P <= 0.03) levels of the volatile lipid oxidation products
      butanal, hexanal, heptanal, and nonanal in the meat during frozen storage but had
      no significant effects on the sensory quality parameters related to odor and
      flavor. The presence of antioxidants in BPM may have reduced lipid oxidation in
      the meat. To conclude, adding BPM to diets reduced the formation of volatile
      lipid oxidation products during frozen storage of the broiler thigh meat. Dynamic
      headspace gas chromatography-mass spectrometry was a more sensitive method in
      detecting early lipid oxidation compared with TBA reactive substances and sensory
      quality analyses in broiler thigh meat.

PMID- 21177462
TI  - Mitochondrial and nuclear markers for the authentication of partridge meat and
      the specific identification of red-legged partridge meat products by polymerase
      chain reaction.
AB  - Two PCR assays for the identification of partridge meat (red-legged partridge,
      chukar partridge, barbary partridge, and gray partridge species) and the specific
      identification of red-legged partridge meat products were developed based on
      species-specific primers targeting the 12S ribosomal RNA mitochondrial gene.
      Moreover, various PCR techniques based on the use of random amplified polymorphic
      DNA markers and nuclear growth hormone and rhodopsin genes were tested to find a
      method for the differentiation between pure and hybrid red-legged partridges.
      Among these techniques, the PCR method based on the amplification and sequencing
      of a nuclear rhodopsin gene fragment was selected as a suitable tool for the
      discrimination among meats from pure and hybrid red-legged partridge individuals.
      The PCR assays reported in this work could be useful in inspection programs to
      verify the correct labeling of raw and heat-treated partridge meat products.

PMID- 21177463
TI  - Field evaluation of the accuracy of vaccine deposition by two different
      commercially available in ovo injection systems.
AB  - The location of injection and vaccine deposition in ovo is known to be critical
      to the efficacy of Marek's disease (MD) vaccine protection against MD viral
      challenge. Vaccine deposition into the amniotic sac or a s.c. or i.m. site of the
      embryo is required for MD vaccine efficacy. Vaccine deposition into the air cell
      or allantoic fluid results in chicks that are not adequately protected against
      subsequent MD viral challenge. A study was conducted in 2 commercial broiler
      hatcheries to evaluate the ability of 2 in ovo injection systems, the Embrex
      Inovoject system (Pfizer Poultry Health, Research Triangle Park, NC) and the
      Intelliject system (Avitech, Salisbury, MD; distributed by Merial Ltd.,
      Gainesville, GA) to deliver a vaccine approved for use in ovo accurately and
      properly. A standard MD vaccine diluent mixed with a protein-staining dye was
      delivered through each machine to simulate in ovo vaccination. The location of
      the dye within the egg determined whether the vaccine was delivered correctly.
      Each egg was also evaluated for normal embryo development (normal eggs). Correct
      vaccine delivery included eggs in which the vaccine was injected into the
      amniotic sac or into s.c. or i.m. regions of the embryo. Incorrect vaccine
      delivery was defined as delivery into the air cell; allantoic sac; any
      combinations including air cell or allantois; the abdominal, cranial, orbital, or
      thoracic cavities of the embryo; or no vaccine delivery at all. In hatchery 1
      (Chick Master, Newton, MS) 1,171 normal eggs were processed through the Inovoject
      system and 1,138 eggs were processed by the Intelliject system. The Inovoject
      system correctly vaccinated 94.62% of the normal eggs as compared with 61.16%
      delivery accuracy of normal eggs with the Intelliject system. In hatchery 2
      (Jamesway Super J, Magee, MS) 926 normal eggs were processed by the Inovoject
      system and 910 normal eggs were processed by the Intelliject system. The
      Inovoject system correctly vaccinated 91.04% of the normal eggs, whereas the
      Intelliject system correctly vaccinated 71.98% of the normal eggs. The results of
      this study clearly demonstrate that the Inovoject system accurately delivered in
      ovo vaccine at a significantly higher rate than the Intelliject system.

PMID- 21177464
TI  - Introduction--the Socially Sustainable Egg Production project.
AB  - The social and political pressure to change egg production from conventional cage
      systems to alternative systems has been largely driven by the desire to provide
      more behavioral freedom for egg-laying hens. However, a change of this magnitude
      can affect other components of the production system and may result in unintended
      outcomes. To understand this issue, a Socially Sustainable Egg Production project
      was formed to 1) conduct a holistic and integrated systematic review of the
      current state of knowledge about various aspects of sustainable egg production,
      and 2) develop a coordinated grant proposal for future extramural funding based
      on the research priorities identified from the review. Expert study groups were
      formed to write evidence-based papers in 5 critical sustainability areas: hen
      health and welfare, economics, food safety and quality, public attitudes, and
      environmental impacts. These papers were presented as the PSA Emerging Issues
      Symposium on Social Sustainability of Egg Production at the 2010 Poultry Science
      Association meeting.

PMID- 21177465
TI  - Sustainability of egg production in the United States--the policy and market
      context.
AB  - The US egg industry is being pressured from many directions to change its
      production practices, particularly to address concerns about hen welfare in
      conventional cage systems. Responding to similar pressures, in 1999, the European
      Union banned conventional laying cages starting in 2012. This now impending
      European ban has led to the development of several alternative housing systems.
      These include noncage systems like aviaries and modified (enriched or furnished)
      cages that include perches, areas in which the hens can forage and dustbathe, and
      nests. Understanding the European experience is valuable as the United States
      considers the future direction of the egg industry. In the United States, the
      proportion of eggs produced in alternative systems is small (less than 5% of
      output) but growing, in part due to market and political incentives for systems
      that provide hens with more behavioral freedom than conventional cages. Animal
      welfare, however, is only one element of a sustainable production system. Other
      elements include those related to public values, the environment, economics,
      worker health, and food safety and quality. Eggs are a primary source of animal
      protein globally, and the United States is the third largest producer of eggs in
      the world, behind China and the European Union. The national table egg flock
      comprises about 280 million hens housed in all regions but with approximately 60%
      of eggs produced in the 10 leading states. Adopting new housing systems will have
      substantial effects on costs and other aspects of egg production on both a
      regional and national scale, with some positive effects but also potential
      negative effects that need to be carefully considered. This paper discusses the
      US egg industry in the context of legislation and standards related to hen
      housing systems. It also addresses initiatives by retailers, nongovernmental
      organizations, and private certification organizations to shape production
      practices in the egg industry as well as how those initiatives might affect
      various aspects of the sustainability of egg production.

PMID- 21177466
TI  - Economic and market issues on the sustainability of egg production in the United
      States: analysis of alternative production systems.
AB  - Conventional cage housing for laying hens evolved as a cost-effective egg
      production system. Complying with mandated hen housing alternatives would raise
      marginal production costs and require sizable capital investment. California data
      indicate that shifts from conventional cages to barn housing would likely cause
      farm-level cost increases of about 40% per dozen. The US data on production costs
      of such alternatives as furnished cages are not readily available and European
      data are not applicable to the US industry structure. Economic analysis relies on
      key facts about production and marketing of conventional and noncage eggs. Even
      if mandated by government or buyers, shifts to alternative housing would likely
      occur with lead times of at least 5 yr. Therefore, egg producers and input
      suppliers would have considerable time to plan new systems and build new
      facilities. Relatively few US consumers now pay the high retail premiums required
      for nonconventional eggs from hens housed in alternative systems. However, data
      from consumer experiments indicate that additional consumers would also be
      willing to pay some premium. Nonetheless, current data do not allow easy
      extrapolation to understand the willingness to pay for such eggs by the vast
      majority of conventional egg consumers. Egg consumption in the United States
      tends to be relatively unresponsive to price changes, such that sustained farm
      price increases of 40% would likely reduce consumption by less than 10%. This
      combination of facts and relationships suggests that, unless low-cost imports
      grew rapidly, requirements for higher cost hen housing systems would raise US egg
      prices considerably while reducing egg consumption marginally. Eggs are a low
      cost source of animal protein and low-income consumers would be hardest hit.
      However, because egg expenditures are a very small share of the consumer budget,
      real income loss for consumers would be small in percentage terms. Finally, the
      high egg prices imposed by alternative hen housing systems raise complex issues
      about linking public policy costs to policy beneficiaries.

PMID- 21177467
TI  - The impact of different housing systems on egg safety and quality.
AB  - A move from conventional cages to either an enriched cage or a noncage system may
      affect the safety or quality, or both, of the eggs laid by hens raised in this
      new environment. The safety of the eggs may be altered either microbiologically
      through contamination of internal contents with Salmonella enterica serovar
      Enteritidis (Salmonella Enteritidis) or other pathogens, or both, or chemically
      due to contamination of internal contents with dioxins, pesticides, or heavy
      metals. Quality may be affected through changes in the integrity of the shell,
      yolk, or albumen along with changes in function, composition, or nutrition.
      Season, hen breed, flock age, and flock disease-vaccination status also interact
      to affect egg safety and quality and must be taken into account. An understanding
      of these different effects is prudent before any large-scale move to an
      alternative housing system is undertaken.

PMID- 21177468
TI  - Environmental impacts and sustainability of egg production systems.
AB  - As part of a systemic assessment toward social sustainability of egg production,
      we have reviewed current knowledge about the environmental impacts of egg
      production systems and identified topics requiring further research. Currently,
      we know that 1) high-rise cage houses generally have poorer air quality and emit
      more ammonia than manure belt (MB) cage houses; 2) manure removal frequency in MB
      houses greatly affects ammonia emissions; 3) emissions from manure storage are
      largely affected by storage conditions, including ventilation rate, manure
      moisture content, air temperature, and stacking profile; 4) more baseline data on
      air emissions from high-rise and MB houses are being collected in the United
      States to complement earlier measurements; 5) noncage houses generally have
      poorer air quality (ammonia and dust levels) than cage houses; 6) noncage houses
      tend to be colder during cold weather due to a lower stocking density than caged
      houses, leading to greater feed and fuel energy use; 7) hens in noncage houses
      are less efficient in resource (feed, energy, and land) utilization, leading to a
      greater carbon footprint; 8) excessive application of hen manure to cropland can
      lead to nutrient runoff to water bodies; 9) hen manure on open (free) range may
      be subject to runoff during rainfall, although quantitative data are lacking; 10)
      mitigation technologies exist to reduce generation and emission of noxious gases
      and dust; however, work is needed to evaluate their economic feasibility and
      optimize design; and 11) dietary modification shows promise for mitigating
      emissions. Further research is needed on 1) indoor air quality, barn emissions,
      thermal conditions, and energy use in alternative hen housing systems (1-story
      floor, aviary, and enriched cage systems), along with conventional housing
      systems under different production conditions; 2) environmental footprint for
      different US egg production systems through life cycle assessment; 3) practical
      means to mitigate air emissions from different production systems; 4) process
      based models for predicting air emissions and their fate; and 5) the interactions
      between air quality, housing system, worker health, and animal health and
      welfare.

PMID- 21177469
TI  - Hen welfare in different housing systems.
AB  - Egg production systems have become subject to heightened levels of scrutiny.
      Multiple factors such as disease, skeletal and foot health, pest and parasite
      load, behavior, stress, affective states, nutrition, and genetics influence the
      level of welfare hens experience. Although the need to evaluate the influence of
      these factors on welfare is recognized, research is still in the early stages. We
      compared conventional cages, furnished cages, noncage systems, and outdoor
      systems. Specific attributes of each system are shown to affect welfare, and
      systems that have similar attributes are affected similarly. For instance,
      environments in which hens are exposed to litter and soil, such as noncage and
      outdoor systems, provide a greater opportunity for disease and parasites. The
      more complex the environment, the more difficult it is to clean, and the larger
      the group size, the more easily disease and parasites are able to spread.
      Environments such as conventional cages, which limit movement, can lead to
      osteoporosis, but environments that have increased complexity, such as noncage
      systems, expose hens to an increased incidence of bone fractures. More space
      allows for hens to perform a greater repertoire of behaviors, although some
      deleterious behaviors such as cannibalism and piling, which results in
      smothering, can occur in large groups. Less is understood about the stress that
      each system imposes on the hen, but it appears that each system has its unique
      challenges. Selective breeding for desired traits such as improved bone strength
      and decreased feather pecking and cannibalism may help to improve welfare. It
      appears that no single housing system is ideal from a hen welfare perspective.
      Although environmental complexity increases behavioral opportunities, it also
      introduces difficulties in terms of disease and pest control. In addition,
      environmental complexity can create opportunities for the hens to express
      behaviors that may be detrimental to their welfare. As a result, any attempt to
      evaluate the sustainability of a switch to an alternative housing system requires
      careful consideration of the merits and shortcomings of each housing system.

PMID- 21177471
TI  - Effect of temperature on postillumination isoprene emission in oak and poplar.
AB  - Isoprene emission from broadleaf trees is highly temperature dependent, accounts
      for much of the hydrocarbon emission from plants, and has a profound effect on
      atmospheric chemistry. We studied the temperature response of postillumination
      isoprene emission in oak (Quercus robur) and poplar (Populus deltoides) leaves in
      order to understand the regulation of isoprene emission. Upon darkening a leaf,
      isoprene emission fell nearly to zero but then increased for several minutes
      before falling back to nearly zero. Time of appearance of this burst of isoprene
      was highly temperature dependent, occurring sooner at higher temperatures. We
      hypothesize that this burst represents an intermediate pool of metabolites,
      probably early metabolites in the methylerythritol 4-phosphate pathway,
      accumulated upstream of dimethylallyl diphosphate (DMADP). The amount of this
      early metabolite(s) averaged 2.9 times the amount of plastidic DMADP. DMADP
      increased with temperature up to 35 degrees C before starting to decrease; in
      contrast, the isoprene synthase rate constant increased up to 40 degrees C, the
      highest temperature at which it could be assessed. During a rapid temperature
      switch from 30 degrees C to 40 degrees C, isoprene emission increased
      transiently. It was found that an increase in isoprene synthase activity is
      primarily responsible for this transient increase in emission levels, while DMADP
      level stayed constant during the switch. One hour after switching to 40 degrees
      C, the amount of DMADP fell but the rate constant for isoprene synthase remained
      constant, indicating that the high temperature falloff in isoprene emission
      results from a reduction in the supply of DMADP rather than from changes in
      isoprene synthase activity.

PMID- 21177472
TI  - Self-incompatibility in Papaver rhoeas activates nonspecific cation conductance
      permeable to Ca2+ and K+.
AB  - Cellular responses rely on signaling. In plant cells, cytosolic free calcium is a
      major second messenger, and ion channels play a key role in mediating
      physiological responses. Self-incompatibility (SI) is an important genetically
      controlled mechanism to prevent self-fertilization. It uses interaction of
      matching S-determinants from the pistil and pollen to allow "self" recognition,
      which triggers rejection of incompatible pollen. In Papaver rhoeas, the S
      determinants are PrsS and PrpS. PrsS is a small novel cysteine-rich protein; PrpS
      is a small novel transmembrane protein. Interaction of PrsS with incompatible
      pollen stimulates S-specific increases in cytosolic free calcium and alterations
      in the actin cytoskeleton, resulting in programmed cell death in incompatible but
      not compatible pollen. Here, we have used whole-cell patch clamping of pollen
      protoplasts to show that PrsS stimulates SI-specific activation of pollen grain
      plasma membrane conductance in incompatible but not compatible pollen grain
      protoplasts. The SI-activated conductance does not require voltage activation,
      but it is voltage sensitive. It is permeable to divalent cations (Ba(2+) >=
      Ca(2+) > Mg(2+)) and the monovalent ions K(+) and NH(4)(+) and is enhanced at
      voltages negative to -100 mV. The Ca(2+) conductance is blocked by La(3+) but not
      by verapamil; the K(+) currents are tetraethylammonium chloride insensitive and
      do not require Ca(2+). We propose that the SI-stimulated conductance may
      represent a nonspecific cation channel or possibly two conductances, permeable to
      monovalent and divalent cations. Our data provide insights into signal-response
      coupling involving a biologically important response. PrsS provides a rare
      example of a protein triggering alterations in ion channel activity.

PMID- 21177473
TI  - The roles of ATP synthase and the cytochrome b6/f complexes in limiting
      chloroplast electron transport and determining photosynthetic capacity.
AB  - In C(3) plants, CO(2) assimilation is limited by ribulose 1,5-bisphosphate (RuBP)
      regeneration rate at high CO(2). RuBP regeneration rate in turn is determined by
      either the chloroplast electron transport capacity to generate NADPH and ATP or
      the activity of Calvin cycle enzymes involved in regeneration of RuBP. Here,
      transgenic tobacco (Nicotiana tabacum 'W38') expressing an antisense gene
      directed at the transcript of either the Rieske iron-sulfur protein of the
      cytochrome (Cyt) b(6)/f complex or the delta-subunit of chloroplast ATP synthase
      have been used to investigate the effect of a reduction of these complexes on
      chloroplast electron transport rate (ETR). Reductions in delta-subunit of ATP
      synthase content did not alter chlorophyll, Cyt b(6)/f complex, or Rubisco
      content, but reduced ETR estimated either from measurements of chlorophyll
      fluorescence or CO(2) assimilation rates at high CO(2). Plants with low ATP
      synthase content exhibited higher nonphotochemical quenching and achieved higher
      ETR per ATP synthase than the wild type. The proportional increase in ETR per ATP
      synthase complex was greatest at 35 degrees C, showing that the ATP synthase
      activity can vary in vivo. In comparison, there was no difference in the ETR per
      Cyt b(6)/f complex in plants with reduced Cyt b(6)/f content and the wild type.
      The ETR decreased more drastically with reductions in Cyt b(6)/f complex than ATP
      synthase content. This suggests that chloroplast ETR is more limited by Cyt
      b(6)/f than ATP synthase content and is a potential target for enhancing
      photosynthetic capacity in crops.

PMID- 21177474
TI  - Crucial role of alkaline sphingomyelinase in sphingomyelin digestion: a study on
      enzyme knockout mice.
AB  - Alkaline sphingomyelinase (alk-SMase) hydrolyses sphingomyelin (SM) to ceramide
      in the gut. To evaluate the physiological importance of the enzyme, we generated
      alk-SMase knockout (KO) mice by the Cre-recombinase-Locus of X-over P1(Cre-LoxP)
      system and studied SM digestion. Both wild-type (WT) and KO mice were fed 3H
      palmitic acid labeled SM together with milk SM by gavage. The lipids in
      intestinal content, intestinal tissues, serum, and liver were analyzed by TLC. In
      KO mice, nondigested 3H-SM in the intestinal content increased by 6-fold and the
      formation of 3H-ceramide decreased markedly, resulting in 98% reduction of 3H
      ceramide/3H-SM ratio 1 h after gavage. The absorbed 3H-palmitic acid portion was
      decreased by 95%. After 3 h, a small increase in 3H-ceramide was identified in
      distal intestine in KO mice. In feces, 3H-SM was increased by 243% and ceramide
      decreased by 74% in the KO mice. The KO mice also showed significantly decreased
      radioactivity in liver and serum. Furthermore, alkaline phosphatase activity in
      the mucosa was reduced by 50% and histological comparison of two female
      littermates preliminarily suggested mucosal hypertrophy in KO mice. This study
      provides definite proof for crucial roles of alk-SMase in SM digestion and points
      to possible roles in regulating mucosal growth and alkaline phosphatase function.

PMID- 21177475
TI  - meso-Transdiene analogs inhibit vesicular monoamine transporter-2 function and
      methamphetamine-evoked dopamine release.
AB  - Lobeline, a nicotinic receptor antagonist and neurotransmitter transporter
      inhibitor, is a candidate pharmacotherapy for methamphetamine abuse. meso
      Transdiene (MTD), a lobeline analog, lacks nicotinic receptor affinity, retains
      affinity for vesicular monoamine transporter 2 (VMAT2), and, surprisingly, has
      enhanced affinity for dopamine (DA) and serotonin transporters [DA transporter
      (DAT) and serotonin transporter (SERT), respectively]. In the current study, MTD
      was evaluated for its ability to decrease methamphetamine self-administration in
      rats relative to food-maintained responding. MTD specifically decreased
      methamphetamine self-administration, extending our previous work. Classical
      structure-activity relationships revealed that more conformationally restricted
      MTD analogs enhanced VMAT2 selectivity and drug likeness, whereas affinity at the
      dihydrotetrabenazine binding and DA uptake sites on VMAT2 was not altered.
      Generally, MTD analogs exhibited 50- to 1000-fold lower affinity for DAT and were
      equipotent or had 10-fold higher affinity for SERT, compared with MTD.
      Representative analogs from the series potently and competitively inhibited
      [(3)H]DA uptake at VMAT2. (3Z,5Z)-3,5-bis(2,4-dichlorobenzylidene)-1
      methylpiperidine (UKMH-106), the 3Z,5Z-2,4-dichlorophenyl MTD analog, had
      improved selectivity for VMAT2 over DAT and importantly inhibited methamphetamine
      evoked DA release from striatal slices. In contrast, (3Z,5E)-3,5-bis(2,4
      dichlorobenzylidene)-1-methylpiperidine (UKMH-105), the 3Z,5E-geometrical isomer,
      inhibited DA uptake at VMAT2, but did not inhibit methamphetamine-evoked DA
      release. Taken together, these results suggest that these geometrical isomers
      interact at alternate sites on VMAT2, which are associated with distinct
      pharmacophores. Thus, structural modification of the MTD molecule resulted in
      analogs exhibiting improved drug likeness and improved selectivity for VMAT2, as
      well as the ability to decrease methamphetamine-evoked DA release, supporting the
      further evaluation of these analogs as treatments for methamphetamine abuse.

PMID- 21177476
TI  - The first universal opioid ligand, (2S)-2-[(5R,6R,7R,14S)-N-cyclopropylmethyl-4,5
      epoxy-6,14-ethano-3-hydroxy-6-methoxymorphinan-7-yl]-3,3-dimethylpentan-2-ol
      (BU08028): characterization of the in vitro profile and in vivo behavioral
      effects in mouse models of acute pain and cocaine-induced reward.
AB  - Certain behavioral features of buprenorphine, including a bell-shaped curve for
      antinociception and attenuation of alcohol consumption, are thought to be
      mediated by activation of nociceptin/orphanin FQ peptide (NOP) receptors, despite
      moderate affinity and low efficacy at NOP receptors. We hypothesized that ligands
      with buprenorphine's physical properties, but possessing increased NOP receptor
      affinity and efficacy, would improve the profile as a drug abuse medication and
      reduce addiction liability. Using this strategy, we designed several compounds
      with universally high affinity, i.e., less than 10 nM at MU, delta, kappa, and
      NOP receptors. Among these, (2S)-2-[(5R,6R,7R,14S)-N-cyclopropylmethyl-4,5-epoxy
      6,14-ethano-3-hydroxy-6-methoxymorphinan-7-yl]-3,3-dimethylpentan-2-ol (BU08028)
      has high affinity at all opioid receptors and increased NOP receptor efficacy in
      vitro in the [35S]GTPgammaS binding assay, however, while still being a partial
      agonist. In vivo, BU08028 was evaluated in an acute thermal antinociception
      assay, for its ability to induce conditioned place preference (CPP), and for its
      effect on cocaine-induced CPP. BU08028 is a very potent long-lasting analgesic.
      It produces an increase in locomotor activity and a significant CPP. As a
      pretreatment to cocaine, BU08028 does not alter cocaine CPP but causes a further
      increase in cocaine-induced locomotor activity. The analgesic, rewarding, and
      stimulant effects are probably caused by MU receptor stimulation. It is likely
      that with BU08028, a partial agonist at both NOP and MU receptors, MU-mediated
      activity overpowers NOP-mediated effects. Thus, it is possible that a different
      buprenorphine analog that is a universal high-affinity opioid ligand but with
      "full agonist" activity at NOP may counteract traditional opioid-mediated effects
      such as antinociception and reward.

PMID- 21177477
TI  - In vitro and in vivo evidence for anti-inflammatory properties of 2
      methoxyestradiol.
AB  - 2-Methoxyestradiol (2MEO) is an endogenous metabolite of 17beta-estradiol that
      interacts with estrogen receptors and microtubules. It has acute anti
      inflammatory activity in animal models that is not attributable to known
      antiproliferative or antiangiogenic actions. Because macrophages are central to
      the innate inflammatory response, we examined whether suppression of macrophage
      activation by 2MEO could account for some of its anti-inflammatory effects.
      Inflammatory mediator production stimulated by lipopolysaccharide (LPS) and
      interferon-gamma in the J774 murine macrophage cell line or human monocytes was
      measured after treatment with 2MEO or the anti-inflammatory agent dexamethasone.
      The effect of these agents on LPS-induced acute lung inflammation in mice was
      also examined. 2MEO suppressed J774 macrophage interleukin-6 and prostaglandin E2
      production (by 30 and 47%, respectively, at 10 MUM) and human monocyte tumor
      necrosis factor-alpha production (by 60% at 3 MUM). Estradiol had no effect on
      J774 macrophage activation, nor did the estrogen receptor antagonist 7alpha-[9
      [(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17beta-diol
      (ICI 182,780) prevent the effects of 2MEO. The actions of 2MEO were not mimicked
      by the microtubule-interfering agents colchicine or paclitaxel. In mice exposed
      to LPS, bronchoalveolar lavage protein content, a measure of vascular leak and
      epithelial injury, was reduced to a comparable extent (~54%) by treatment with
      2MEO (150 mg . kg-1) or dexamethasone (1 mg . kg-1). In addition, 2MEO reduced
      LPS-induced interleukin-6 gene expression. Thus, 2MEO modulates macrophage
      activation in vitro and has high-dose acute anti-inflammatory activity in vivo.
      These findings are consistent with the acute anti-inflammatory actions of 2MEO
      being mediated in part by the suppression of macrophage activation.

PMID- 21177478
TI  - Diosgenin modulates vascular smooth muscle cell function by regulating cell
      viability, migration, and calcium homeostasis.
AB  - In this study, we compared the potencies of diosgenin, a plant-derived sapogenin
      structurally similar to estrogen and progesterone, on vascular smooth muscle
      functions ranging from contraction and migration to apoptosis. The effects of
      diosgenin on vascular smooth muscle cell viability and migration were measured
      using a primary mouse aortic smooth muscle cell culture. The effects of diosgenin
      on smooth muscle cell contraction and calcium signaling were investigated in the
      isolated mouse aorta using wire myography and confocal microscopy, respectively.
      Here, we report that in cultured cells diosgenin (>= 25 MUM) induces apoptosis as
      measured by the number of annexin V-positive cells and caspase-3 cleavage, while
      decreasing cell viability as indicated by protein kinase B/Akt phosphorylation.
      In addition, diosgenin blocks smooth muscle cell migration in a transwell Boyden
      chamber in response to serum treatment and response to injury in a cell culture
      system. Diosgenin (>= 25 MUM) also significantly blocks receptor-mediated calcium
      signals and smooth muscle contraction in the isolated aorta. There is no
      difference in the inhibitory effects of diosgenin on vascular smooth muscle
      contraction between the endothelium-intact and endothelium-denuded aortic
      segments, indicating that they are caused by altered smooth muscle activity. Our
      findings suggest that over the concentration range of 10 to 15 MUM diosgenin may
      provide overall beneficial effects on diseased vascular smooth muscle cells by
      blocking migration and contraction without any significant cytopathic effects,
      implying a potential therapeutic value for diosgenin in vascular disorders.

PMID- 21177479
TI  - Serine protease inhibitors specifically defend Solanum nigrum against generalist
      herbivores but do not influence plant growth and development.
AB  - Solanaceaeous taxa produce diverse peptide serine proteinase inhibitors (SPIs),
      known antidigestive defenses that might also control endogenous plant proteases.
      If and how a plant coordinates and combines its different SPIs for the defense
      against herbivores and if these SPIs simultaneously serve developmental functions
      is unknown. We examine Solanum nigrum's SPI profile, comprising four different
      active inhibitors, of which the most abundant proved to be novel, to understand
      their functional specialization in an ecological context. Transcript and activity
      characterization revealed tissue-specific and insect-elicited accumulation
      patterns. Stable and transient gene silencing of all four SPIs revealed different
      specificities for target proteinases: the novel SPI2c displayed high specificity
      for trypsin and chymotrypsin, while two other SPI2 homologs were highly active
      against subtilisin. In field and lab experiments, we found all four SPIs to
      display herbivore- and gene-specific defensive properties, with dissimilar
      effects on closely related species. However, we did not observe any clear
      developmental phenotype in SPI-silenced plants, suggesting that SPIs do not play
      a major role in regulating endogenous proteases under the conditions studied. In
      summary, specific single SPIs or their combinations defend S. nigrum against
      generalist herbivores, while the defense against herbivores specialized on SPI
      rich diets requires other unknown defense mechanisms.

PMID- 21177480
TI  - miR156-targeted and nontargeted SBP-box transcription factors act in concert to
      secure male fertility in Arabidopsis.
AB  - The SBP-box transcription factor SQUAMOSA PROMOTER BINDING PROTEIN-LIKE8 (SPL8)
      is required for proper development of sporogenic tissues in Arabidopsis thaliana.
      Here, we show that the semisterile phenotype of SPL8 loss-of-function mutants is
      due to partial functional redundancy with several other members of the
      Arabidopsis SPL gene family. In contrast with SPL8, the transcripts of these
      latter SPL genes are all targeted by miR156/7. Whereas the introduction of single
      miR156/7-resistant SPL transgenes could only partially restore spl8 mutant
      fertility, constitutive overexpression of miR156 in an spl8 mutant background
      resulted in fully sterile plants. Histological analysis of the anthers of such
      sterile plants revealed an almost complete absence of sporogenous and anther wall
      tissue differentiation, a phenotype similar to that reported for
      sporocyteless/nozzle (spl/nzz) mutant anthers. Expression studies indicated a
      functional requirement for miR156/7-targeted SPL genes limited to early anther
      development. Accordingly, several miR156/7-encoding loci were found expressed in
      anther tissues at later stages of development. We conclude that fully fertile
      Arabidopsis flowers require the action of multiple miR156/7-targeted SPL genes in
      concert with SPL8. Either together with SPL/NZZ or independently, these SPL genes
      act to regulate genes mediating cell division, differentiation, and specification
      early in anther development. Furthermore, SPL8 in particular may be required to
      secure fertility of the very first flowers when floral transition-related
      miR156/7 levels might not have sufficiently declined.

PMID- 21177481
TI  - Structure-function analyses of a caffeic acid O-methyltransferase from perennial
      ryegrass reveal the molecular basis for substrate preference.
AB  - Lignin forms from the polymerization of phenylpropanoid-derived building blocks
      (the monolignols), whose modification through hydroxylation and O-methylation
      modulates the chemical and physical properties of the lignin polymer. The enzyme
      caffeic acid O-methyltransferase (COMT) is central to lignin biosynthesis. It is
      often targeted in attempts to engineer the lignin composition of transgenic
      plants for improved forage digestibility, pulping efficiency, or utility in
      biofuel production. Despite intensive investigation, the structural determinants
      of the regiospecificity and substrate selectivity of COMT remain poorly defined.
      Reported here are x-ray crystallographic structures of perennial ryegrass (Lolium
      perenne) COMT (Lp OMT1) in open conformational state, apo- and holoenzyme forms
      and, most significantly, in a closed conformational state complexed with the
      products S-adenosyl-L-homocysteine and sinapaldehyde. The product-bound complex
      reveals the post-methyl-transfer organization of COMT's catalytic groups with
      reactant molecules and the fully formed phenolic-ligand binding site. The core
      scaffold of the phenolic ligand forges a hydrogen-bonding network involving the 4
      hydroxy group that anchors the aromatic ring and thereby permits only
      metahydroxyl groups to be positioned for transmethylation. While distal from the
      site of transmethylation, the propanoid tail substituent governs the kinetic
      preference of ryegrass COMT for aldehydes over alcohols and acids due to a single
      hydrogen bond donor for the C9 oxygenated moiety dictating the preference for an
      aldehyde.

PMID- 21177482
TI  - A recycling-defective vacuolar sorting receptor reveals an intermediate
      compartment situated between prevacuoles and vacuoles in tobacco.
AB  - Plant vacuolar sorting receptors (VSRs) display cytosolic Tyr motifs (YMPL) for
      clathrin-mediated anterograde transport to the prevacuolar compartment. Here, we
      show that the same motif is also required for VSR recycling. A Y612A point
      mutation in Arabidopsis thaliana VSR2 leads to a quantitative shift in VSR2
      steady state levels from the prevacuolar compartment to the trans-Golgi network
      when expressed in Nicotiana tabacum. By contrast, the L615A mutant VSR2 leaks
      strongly to vacuoles and accumulates in a previously undiscovered compartment.
      The latter is shown to be distinct from the Golgi stacks, the trans-Golgi
      network, and the prevacuolar compartment but is characterized by high
      concentrations of soluble vacuolar cargo and the rab5 GTPase Rha1(RabF2a). The
      results suggest that the prevacuolar compartment matures by gradual receptor
      depletion, leading to the formation of a late prevacuolar compartment situated
      between the prevacuolar compartment and the vacuole.

PMID- 21177484
TI  - IL-7-dependent STAT-5 activation and CD8+ T cell proliferation are impaired in
      HIV infection.
AB  - This study tests the hypothesis that IL-7 signaling and activity of CD8(+) T
      cells are impaired in HIV infection. IL-7 is necessary for optimal CTL activity
      and T cell survival and proliferation. Defects in IL-7R signaling may contribute
      to impaired activity of IL-7 observed in progressive HIV disease. A decreased
      proportion of CD8(+) T cells expressing the IL-7Ralpha chain (CD127) in
      progressive HIV disease would be expected to affect IL-7 activity. Alternatively,
      disease-associated defects of remaining CD8(+)CD127(+) T cells may influence IL-7
      responsiveness. Therefore, the IL-7 responsiveness of CD8(+)CD127(+) T cells from
      HIV(-) and untreated or treated HIV(+) individuals was investigated. Blood was
      collected from HIV(-) and untreated or effectively treated HIV(+) (<50 viral
      copies/ml for >1 year) individuals, and CD8(+)CD127(+) T cells were isolated and
      cultured with IL-7. Indicators of IL-7 signaling (P-STAT5) and activity (Bcl-2
      and proliferation) were evaluated by flow cytometry. Isolated CD8(+)CD127(+) T
      cells from untreated HIV(+) individuals expressed significantly less P-STAT5 in
      response to IL-7 compared with CD8(+)CD127(+) T cells from HIV(-) individuals. In
      effectively treated HIV(+) individuals, CD8(+)CD127(+) T cells also expressed
      significantly lower levels of P-STAT5 compared with HIV(-) individuals. IL-7
      dependent proliferation of CD8(+)CD127(+) T cells from untreated HIV(+)
      individuals was similarly impaired. In contrast, IL-7-induced Bcl-2 expression
      was not impaired in CD8(+)CD127(+) T cells from HIV(+) individuals. These data
      demonstrate that IL-7/IL-7R dysfunction in HIV infection may contribute to IL-7
      specific signaling defects. Decreased, IL-7-dependent activation of STAT5 and
      impaired proliferation may negatively impact the maintenance of CD8(+) T cell
      responsiveness in HIV infection.

PMID- 21177485
TI  - Glucuronidation of the red clover isoflavone irilone by liver microsomes from
      different species and human UDP-glucuronosyltransferases.
AB  - Red clover (Trifolium pratense L.) is used as a source for isoflavone (IF)
      dietary supplements. In this study, we focused on the red clover IF irilone
      (IRI), because of its reported comparatively high bioavailability. Because the
      conjugative metabolism plays a key role in the elimination of IF, we investigated
      the species-specific differences and glucuronidation kinetics of IRI using
      different liver microsomes as well as the recombinant UDP
      glucuronosyltransferases (UGTs) 1A1, 1A7, 1A8, 1A9, 1A10, and 2B15. Both possible
      monoglucuronides, the IRI-O-4'-monoglucuronide (IRI-G4') and the IRI-O-5
      monoglucuronide (IRI-G5), were detected. Human liver microsomes (HLM) as well as
      rat liver microsomes predominantly formed IRI-G5, whereas for porcine liver
      microsomes, IRI-G4' prevailed. HLM showed an apparent V(max) value of 0.43
      nmol/min . mg and an apparent K(m) value of 9.8 MUM for the formation of IRI-G5
      and a V(max) of 0.35 nmol/min . mg and a K(m) of 64.7 MUM in the case of IRI-G4'.
      Formation of both glucuronides was best fit using the substrate inhibition
      equation. The glucuronidation of IRI by UGTs led to values for the intrinsic
      clearance varying between 4 and 100 ml/min . mg, with UGT1A7 showing the lowest
      and UGT1A10 the highest IRI conversion rate. The results indicate that IRI
      undergoes an efficient glucuronidation, presumably in the intestine and liver,
      following atypical kinetic profiles.

PMID- 21177483
TI  - Nucleocytoplasmic distribution is required for activation of resistance by the
      potato NB-LRR receptor Rx1 and is balanced by its functional domains.
AB  - The Rx1 protein, as many resistance proteins of the nucleotide binding-leucine
      rich repeat (NB-LRR) class, is predicted to be cytoplasmic because it lacks
      discernable nuclear targeting signals. Here, we demonstrate that Rx1, which
      confers extreme resistance to Potato virus X, is located both in the nucleus and
      cytoplasm. Manipulating the nucleocytoplasmic distribution of Rx1 or its elicitor
      revealed that Rx1 is activated in the cytoplasm and cannot be activated in the
      nucleus. The coiled coil (CC) domain was found to be required for accumulation of
      Rx1 in the nucleus, whereas the LRR domain promoted the localization in the
      cytoplasm. Analyses of structural subdomains of the CC domain revealed no
      autonomous signals responsible for active nuclear import. Fluorescence recovery
      after photobleaching and nuclear fractionation indicated that the CC domain binds
      transiently to large complexes in the nucleus. Disruption of the Rx1 resistance
      function and protein conformation by mutating the ATP binding phosphate binding
      loop in the NB domain, or by silencing the cochaperone SGT1, impaired the
      accumulation of Rx1 protein in the nucleus, while Rx1 versions lacking the LRR
      domain were not affected in this respect. Our results support a model in which
      interdomain interactions and folding states determine the nucleocytoplasmic
      distribution of Rx1.

PMID- 21177486
TI  - Pharmacokinetics, metabolism, and disposition of rivoglitazone, a novel
      peroxisome proliferator-activated receptor gamma agonist, in rats and monkeys.
AB  - The pharmacokinetics, metabolism, and excretion of rivoglitazone [(RS)-5-{4-[(6
      methoxy-1-methyl-1H-benzimidazol-2-yl)methoxy]benzyl}-1,3-thiazolidine-2,4-dione
      monohydrochloride], a novel thiazolidinedione (TZD) peroxisome proliferator
      activated receptor gamma selective agonist, were evaluated in male F344/DuCrlCrlj
      rats and cynomolgus monkeys. The total body clearance and volume of distribution
      of rivoglitazone were low in both animals (0.329-0.333 ml per min/kg and 0.125
      0.131 l/kg for rats and 0.310-0.371 ml per min/kg and 0.138-0.166 l/kg for
      monkeys), and the plasma half-life was 4.55 to 4.84 h for rats and 6.21 to 6.79 h
      for monkeys. The oral bioavailability was high (>95% in rats and >76.1% in
      monkeys), and the exposure increased dose proportionally. After administration of
      [(14)C]rivoglitazone, radioactivity was mainly excreted in feces in rats, whereas
      radioactivity was excreted in urine and feces with the same ratio in monkeys.
      Because excreted rivoglitazone in urine and bile was low, metabolism was
      predicted to be the main contributor to total body clearance. The structures of
      20 metabolites (M1-M20) were identified, and 5 initial metabolic pathways were
      proposed: O-demethylation, TZD ring opening, N-glucuronidation, N-demethylation,
      and TZD ring hydroxylation. O-Demethylation was the main metabolic pathway in
      both animals, but N-demethylation and TZD ring hydroxylation were observed only
      in monkeys. N-Glucuronide (M13) was nonenzymatically hydrolyzed to TZD ring
      opened N-glucuronide (M9), and the amount of these metabolites in monkeys was
      larger than that in rats. In plasma, rivolitazone was observed as the main
      component in both animals, and O-demethyl-O-sulfate (M11) was observed as the
      major metabolite in rats but as many minor metabolites in monkeys.

PMID- 21177487
TI  - In vitro metabolism of oxymetazoline: evidence for bioactivation to a reactive
      metabolite.
AB  - Oxymetazoline (6-tert-butyl-3-(2-imidazolin-2-ylmethyl)-2,4-dimethylphenol) has
      been widely used as a nonprescription nasal vasoconstrictor for >40 years;
      however, its metabolic pathway has not been investigated. This study describes
      the in vitro metabolism of oxymetazoline in human, rat, and rabbit liver
      postmitochondrial supernatant fraction from homogenized tissue (S9) fractions and
      their microsomes supplemented with NADPH. The metabolites of oxymetazoline
      identified by liquid chromatography (LC)/UV/tandem mass spectrometry (MS/MS),
      included M1 (monohydroxylation of the t-butyl group), M2 (oxidative
      dehydrogenation of the imidazoline to an imidazole moiety), M3 (monohydroxylation
      of M2), M4 (dihydroxylation of oxymetazoline), and M5 (dihydroxylation of M2).
      Screening with nine human expressed cytochromes P450 (P450s) identified CYP2C19
      as the single P450 isoform catalyzing the formation of M1, M2, and M3.
      Glutathione conjugates of oxymetazoline (M6) and M2 (M7) were identified in the
      liver S9 fractions, indicating the capability of oxymetazoline to undergo
      bioactivation to reactive intermediate species. M6 and M7 were not detected in
      those liver S9 incubations without NADPH. Cysteine conjugates (M8 and M9) derived
      from glutathione conjugates and hydroxylated glutathione conjugates (M10 and M11)
      were also identified. The reactive intermediate of oxymetazoline was trapped with
      glutathione and N-acetyl cysteine and identified by LC/MS/MS. M6 was isolated and
      identified by one-dimensional or two-dimensional NMR as the glutathione conjugate
      of a p-quinone methide. We have shown the tendency of oxymetazoline to form p
      quinone methide species via a bioactivation mechanism involving a CYP2C19
      catalyzed two-electron oxidation. Nevertheless, we conclude that the formation of
      this reactive species might not be a safety concern for oxymetazoline nasal
      products because of the typical low-dose and brief dosage regimen limited to
      nasal delivery.

PMID- 21177488
TI  - Two species of Strobilomyces (Boletaceae, Boletales), S. seminudus and S. hongoi
      sp. nov. from Japan.
AB  - We describe and illustrate two Strobilomyces species, S. seminudus and S. hongoi
      sp. nov. These two species have been confused and treated as a single species
      (i.e. S. seminudus). However recent studies based on population genetics have
      implied that they are reproductively isolated. In the present study we found that
      they are phylogenetically and morphologically distinct. The molecular
      phylogenetic trees inferred from the partial sequences of the largest subunit of
      RNA polymerase II (RPB1) and the second-largest subunit of RNA polymerase II
      (RPB2) support the differentiation of these two species as well as their
      differentiation from other related species. Strobilomyces seminudus is
      characterized by a stipe with an annular zone, becoming distinctly thickened near
      the apex and mottled with appressed-tomentose scales near the base. In contrast
      S. hongoi is characterized by a stipe with a remarkable reticulum at the upper
      and middle part and with minutely warty scales downward. Stipe characteristics
      also are useful for distinguishing these two species from other related species.
      In addition the incompletely reticulated basidiospores of these two species are
      also distinct from those of related species (i.e. S. foveatus).

PMID- 21177489
TI  - A new species of Heliocephala from Mexico with an assessment of the systematic
      positions of the anamorph genera Heliocephala and Holubovaniella.
AB  - During a study of the microfungi on decaying leaves collected in Mexico we
      encountered a fungus sharing features of the anamorph genera Heliocephala and
      Holubovaniella. This hyphomycete resembled Hol. elegans in possessing obclavate
      to fusiform, three-septate, rostrate phragmoconidia, but it can be distinguished
      by its much shorter, branched, determinate conidiophores. Unlike members of genus
      Heliocephala, which also possess determinant conidiophores, the phragmoconidia of
      this taxon are short-rostrate and have not been observed to germinate
      iteratively. Prompted by the discovery of this hyphomycete, we investigated the
      phylogenetic relationships among species of Heliocephala and Holubovaniella.
      Analysis of large subunit rDNA gene sequences positioned species of Heliocephala
      and Holubovaniella in the Dothideomycetes and identified Stomiopeltis betulae
      (Micropeltididaceae) as their closest relative. These results also indicated that
      Heliocephala and Holubovaniella are closely related taxa. Based on these findings
      and the similarity of the developmental and morphological characters of species
      of Heliocephala and Holubovaniella, we recognize these genera as synonymous and
      describe a new species, Heliocephala triseptata. A dichotomous key to the species
      of Heliocephala is provided.

PMID- 21177490
TI  - Gibberella musae (Fusarium musae) sp. nov., a recently discovered species from
      banana is sister to F. verticillioides.
AB  - Several strains of Fusarium isolated from banana were identified previously as F.
      verticillioides (Sacc.) Nirenberg but described as unable to produce fumonisin.
      Here we report biochemical and morphological evidence, as well as multilocus
      phylogenetic analyses based on elongation factor (EF-1alpha), calmodulin, beta
      tubulin, and the second largest subunit of RNA polymerase II (RPB2) sequences,
      indicating that these isolates represent a unique lineage in the Gibberella
      fujikuroi species complex related to but distinct from F. verticillioides.
      Together with previous results of molecular studies, as well as with results of
      metabolite analyses, crossing experiments, pathogenicity tests and morphological
      characterization, these new data indicate that these strains isolated from banana
      represent a new species, Gibberella musae Van Hove et al. sp. nov. (anamorph:
      Fusarium musae Van Hove et al. sp. nov.), which is described herein.

PMID- 21177491
TI  - T cell receptor signaling kinetics takes the stage.
AB  - It has been long surmised that the strength of stimulation of the T cell receptor
      (TCR) determines the robustness of TCR-mediated signaling and the magnitude of a
      T cell response. However, it is becoming evident that the signal from the TCR
      develops over time to approach its steady-state, affinity-determined maximal
      extent and that variations in this time have a substantial effect on the
      responsiveness of T cells. Here, I discuss data that show that the kinetics of
      signal propagation in various segments of the TCR signaling network can influence
      the spatiotemporal regulation of the effector functions of T cells and the
      quality of the T cell response.

PMID- 21177492
TI  - Mechanosomes carry a loaded message.
AB  - Understanding the molecular mechanisms that mediate the response of cells to
      mechanical stimuli, the process known as mechanotransduction, has emerged as a
      research topic with relevance to human health and disease. Mechanotransduction in
      bone is particularly relevant because the mammalian skeleton remodels to adapt to
      its loading environment The mechanosome hypothesis has been proposed to explain
      how mechanical signals detected at the bone cell membrane are converted into
      changes in transcription of target genes. In one model, adhesion complexes at the
      surface of the sensor cell activate multiprotein complexes (mechanosomes) that
      include both proteins involved in adhesion and transcription factors that move to
      the nucleus and regulate transcriptional activity of target genes. New work has
      identified a previously unknown mechanotransduction complex-consisting of nitric
      oxide (NO), cyclic guanosine monophosphate (cGMP), protein kinase G II, SHP-1,
      and SHP-2-that associates with beta3 integrins through Src. This complex
      regulates gene expression in response to fluid flow and has several of the
      necessary elements of a mechanosome complex. These findings beg the question of
      just how extensive the mechanosome network is and how mechanosomes interact with
      other signal transduction pathways that also respond to mechanical load.

PMID- 21177493
TI  - The mammalian MAPK/ERK pathway exhibits properties of a negative feedback
      amplifier.
AB  - Three-tiered kinase modules, such as the Raf-MEK (mitogen-activated or
      extracellular signal-regulated protein kinase kinase)-ERK (extracellular signal
      regulated kinase) mitogen-activated protein kinase pathway, are widespread in
      biology, suggesting that this structure conveys evolutionarily advantageous
      properties. We show that the three-tiered kinase amplifier module combined with
      negative feedback recapitulates the design principles of a negative feedback
      amplifier (NFA), which is used in electronic circuits to confer robustness,
      output stabilization, and linearization of nonlinear signal amplification. We
      used mathematical modeling and experimental validation to demonstrate that the
      ERK pathway has properties of an NFA that (i) converts intrinsic switch-like
      activation kinetics into graded linear responses, (ii) conveys robustness to
      changes in rates of reactions within the NFA module, and (iii) stabilizes outputs
      in response to drug-induced perturbations of the amplifier. These properties
      determine biological behavior, including activation kinetics and the response to
      drugs.

PMID- 21177494
TI  - Cyclic GMP and protein kinase G control a Src-containing mechanosome in
      osteoblasts.
AB  - Mechanical stimulation is crucial for bone growth and remodeling, and fluid shear
      stress promotes anabolic responses in osteoblasts through multiple second
      messengers, including nitric oxide (NO). NO triggers production of cyclic
      guanosine 3',5'-monophosphate (cGMP), which in turn activates protein kinase G
      (PKG). We found that the NO-cGMP-PKG signaling pathway activates Src in
      mechanically stimulated osteoblasts to initiate a proliferative response. PKGII
      was necessary for Src activation, a process that also required the interaction of
      Src with beta3 integrins and dephosphorylation of Src by a complex containing the
      phosphatases SHP-1 (Src homology 2 domain-containing tyrosine phosphatase 1) and
      SHP-2. PKGII directly phosphorylated and stimulated SHP-1 activity, and fluid
      shear stress triggered the recruitment of PKGII, Src, SHP-1, and SHP-2 to a
      mechanosome containing beta3 integrins. PKGII-null mice showed defective Src and
      ERK (extracellular signal-regulated kinase) signaling in osteoblasts and
      decreased ERK-dependent gene expression in bone. Our findings reveal a
      convergence of NO-cGMP-PKG and integrin signaling and establish a previously
      unknown mechanism of Src activation. These results support the use of PKG
      activating drugs to mimic the anabolic effects of mechanical stimulation of bone
      in the treatment of osteoporosis.

PMID- 21177495
TI  - Phosphoproteomic analysis reveals interconnected system-wide responses to
      perturbations of kinases and phosphatases in yeast.
AB  - The phosphorylation and dephosphorylation of proteins by kinases and phosphatases
      constitute an essential regulatory network in eukaryotic cells. This network
      supports the flow of information from sensors through signaling systems to
      effector molecules and ultimately drives the phenotype and function of cells,
      tissues, and organisms. Dysregulation of this process has severe consequences and
      is one of the main factors in the emergence and progression of diseases,
      including cancer. Thus, major efforts have been invested in developing specific
      inhibitors that modulate the activity of individual kinases or phosphatases;
      however, it has been difficult to assess how such pharmacological interventions
      would affect the cellular signaling network as a whole. Here, we used label-free,
      quantitative phosphoproteomics in a systematically perturbed model organism
      (Saccharomyces cerevisiae) to determine the relationships between 97 kinases, 27
      phosphatases, and more than 1000 phosphoproteins. We identified 8814 regulated
      phosphorylation events, describing the first system-wide protein phosphorylation
      network in vivo. Our results show that, at steady state, inactivation of most
      kinases and phosphatases affected large parts of the phosphorylation-modulated
      signal transduction machinery-and not only the immediate downstream targets. The
      observed cellular growth phenotype was often well maintained despite the
      perturbations, arguing for considerable robustness in the system. Our results
      serve to constrain future models of cellular signaling and reinforce the idea
      that simple linear representations of signaling pathways might be insufficient
      for drug development and for describing organismal homeostasis.

PMID- 21177496
TI  - Re"evolutionary" regenerative medicine.

PMID- 21177497
TI  - The cover. Madonna and child.

PMID- 21177498
TI  - A piece of my mind. The day the computer tried to eat my alligator.

PMID- 21177499
TI  - Findings on youth injuries bolster case for helmet use by all motorcycle riders.

PMID- 21177500
TI  - Panel backs wider pertussis vaccination to curb outbreaks, prevent deaths.

PMID- 21177501
TI  - Withdrawal of infant cold medicines decreases ED visits by half, CDC finds.

PMID- 21177502
TI  - Association of risk-reducing surgery with cancer risks and mortality in BRCA
      mutation carriers.

PMID- 21177503
TI  - Regionalized perinatal care systems and very low-birth-weight and very preterm
      infants.

PMID- 21177504
TI  - Shared and physician-directed decision making in clinical practice.

PMID- 21177505
TI  - Association of a leukemic stem cell gene expression signature with clinical
      outcomes in acute myeloid leukemia.
AB  - CONTEXT: In many cancers, specific subpopulations of cells appear to be uniquely
      capable of initiating and maintaining tumors. The strongest support for this
      cancer stem cell model comes from transplantation assays in immunodeficient mice,
      which indicate that human acute myeloid leukemia (AML) is driven by self-renewing
      leukemic stem cells (LSCs). This model has significant implications for the
      development of novel therapies, but its clinical relevance has yet to be
      determined. OBJECTIVE: To identify an LSC gene expression signature and test its
      association with clinical outcomes in AML. DESIGN, SETTING, AND PATIENTS:
      Retrospective study of global gene expression (microarray) profiles of LSC
      enriched subpopulations from primary AML and normal patient samples, which were
      obtained at a US medical center between April 2005 and July 2007, and validation
      data sets of global transcriptional profiles of AML tumors from 4 independent
      cohorts (n = 1047). MAIN OUTCOME MEASURES: Identification of genes discriminating
      LSC-enriched populations from other subpopulations in AML tumors; and association
      of LSC-specific genes with overall, event-free, and relapse-free survival and
      with therapeutic response. RESULTS: Expression levels of 52 genes distinguished
      LSC-enriched populations from other subpopulations in cell-sorted AML samples. An
      LSC score summarizing expression of these genes in bulk primary AML tumor samples
      was associated with clinical outcomes in the 4 independent patient cohorts. High
      LSC scores were associated with worse overall, event-free, and relapse-free
      survival among patients with either normal karyotypes or chromosomal
      abnormalities. For the largest cohort of patients with normal karyotypes (n =
      163), the LSC score was significantly associated with overall survival as a
      continuous variable (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.08
      1.22; log-likelihood P <.001). The absolute risk of death by 3 years was 57% (95%
      CI, 43%-67%) for the low LSC score group compared with 78% (95% CI, 66%-86%) for
      the high LSC score group (HR, 1.9 [95% CI, 1.3-2.7]; log-rank P = .002). In
      another cohort with available data on event-free survival for 70 patients with
      normal karyotypes, the risk of an event by 3 years was 48% (95% CI, 27%-63%) in
      the low LSC score group vs 81% (95% CI, 60%-91%) in the high LSC score group (HR,
      2.4 [95% CI, 1.3-4.5]; log-rank P = .006). In multivariate Cox regression
      including age, mutations in FLT3 and NPM1, and cytogenetic abnormalities, the HRs
      for LSC score in the 3 cohorts with data on all variables were 1.07 (95% CI, 1.01
      1.13; P = .02), 1.10 (95% CI, 1.03-1.17; P = .005), and 1.17 (95% CI, 1.05-1.30;
      P = .005). CONCLUSION: High expression of an LSC gene signature is independently
      associated with adverse outcomes in patients with AML.

PMID- 21177506
TI  - Prenatal micronutrient supplementation and intellectual and motor function in
      early school-aged children in Nepal.
AB  - CONTEXT: Iron and zinc are important for the development of both intellectual and
      motor skills. Few studies have examined whether iron and zinc supplementation
      during gestation, a critical period of central nervous system development,
      affects children's later functioning. OBJECTIVE: To examine intellectual and
      motor functioning of children whose mothers received micronutrient
      supplementation during pregnancy. DESIGN, SETTING, AND PARTICIPANTS: Cohort
      follow-up of 676 children aged 7 to 9 years in June 2007-April 2009 who had been
      born to women in 4 of 5 groups of a community-based, double-blind, randomized
      controlled trial of prenatal micronutrient supplementation between 1999 and 2001
      in rural Nepal. Study children were also in the placebo group of a subsequent
      preschool iron and zinc supplementation trial. INTERVENTIONS: Women whose
      children were followed up had been randomly assigned to receive daily iron/folic
      acid, iron/folic acid/zinc, or multiple micronutrients containing these plus 11
      other micronutrients, all with vitamin A, vs a control group of vitamin A alone
      from early pregnancy through 3 months postpartum. These children did not receive
      additional micronutrient supplementation other than biannual vitamin A
      supplementation. MAIN OUTCOME MEASURES: Children's intellectual functioning,
      assessed using the Universal Nonverbal Intelligence Test (UNIT); tests of
      executive function, including go/no-go, the Stroop test, and backward digit span;
      and motor function, assessed using the Movement Assessment Battery for Children
      (MABC) and finger-tapping test. RESULTS: The difference across outcomes was
      significant (Bonferroni-adjusted P < .001) for iron/folic acid vs control but not
      for other supplement groups. The mean UNIT T score in the iron/folic acid group
      was 51.7 (SD, 8.5) and in the control group was 48.2 (SD, 10.2), with an adjusted
      mean difference of 2.38 (95% confidence interval [CI], 0.06-4.70; P = .04).
      Differences were not significant between the control group and either the
      iron/folic acid/zinc (0.73; 95% CI, -0.95 to 2.42) or multiple micronutrient
      (1.00; 95% CI, -0.55 to 2.56) groups. In tests of executive function, scores were
      better in the iron/folic acid group relative to the control group for the Stroop
      test (adjusted mean difference in proportion who failed, -0.14; 95% CI, -0.23 to 
      0.04) and backward digit span (adjusted mean difference, 0.36; 95% CI, 0.01-0.71)
      but not for the go/no-go test. The MABC score was lower (better) in the
      iron/folic acid group compared with the control group but not after adjustment
      for confounders (mean difference, -1.47; 95% CI, -3.06 to 0.12; P = .07). Finger
      tapping test scores were higher (mean difference, 2.05; 95% CI, 0.87-3.24; P =
      .001) in the iron/folic acid group. CONCLUSION: Aspects of intellectual
      functioning including working memory, inhibitory control, and fine motor
      functioning among offspring were positively associated with prenatal iron/folic
      acid supplementation in an area where iron deficiency is prevalent. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00115271.

PMID- 21177508
TI  - A behavioral and systems view of professionalism.
AB  - Professionalism may not be sufficient to drive the profound and far-reaching
      changes needed in the US health care system, but without it, the health care
      enterprise is lost. Formal statements defining professionalism have been abstract
      and principle based, without a clear description of what professional behaviors
      look like in practice. This article proposes a behavioral and systems view of
      professionalism that provides a practical approach for physicians and the
      organizations in which they work. A more behaviorally oriented definition makes
      the pursuit of professionalism in daily practice more accessible and attainable.
      Professionalism needs to evolve from being conceptualized as an innate character
      trait or virtue to sophisticated competencies that can and must be taught and
      refined over a lifetime of practice. Furthermore, professional behaviors are
      profoundly influenced by the organizational and environmental context of
      contemporary medical practice, and these external forces need to be harnessed to
      support--not inhibit--professionalism in practice. This perspective on
      professionalism provides an opportunity to improve the delivery of health care
      through education and system-level reform.

PMID- 21177507
TI  - Germline epigenetic regulation of KILLIN in Cowden and Cowden-like syndrome.
AB  - CONTEXT: Germline loss-of-function phosphatase and tensin homolog gene (PTEN)
      mutations cause 80% of Cowden syndrome, a rare autosomal-dominant disorder (1 in
      200,000 live births), characterized by high risks of breast, thyroid, and other
      cancers. A large heterogeneous group of individuals with Cowden-like syndrome,
      who have various combinations of Cowden syndrome features but who do not meet
      Cowden syndrome diagnostic criteria, have PTEN mutations less than 10% of the
      time, making molecular diagnosis, prediction, genetic counseling, and risk
      management challenging. Other mechanisms of loss of function such as
      hypermethylation, which should result in underexpression of PTEN or of KILLIN, a
      novel tumor suppressor transcribed in the opposite direction, may account for the
      remainder of Cowden syndrome and Cowden-like syndrome. OBJECTIVE: To determine
      whether germline methylation is found in Cowden syndrome or Cowden-like syndrome
      in individuals lacking germline PTEN mutations. DESIGN, SETTING, AND
      PARTICIPANTS: Nucleic acids from prospective nested series of 123 patients with
      Cowden syndrome or Cowden-like syndrome and 50 unaffected individuals without
      PTEN variants were analyzed for germline methylation and expression of PTEN and
      KILLIN at the Cleveland Clinic, August 2008-June 2010. Prevalence of component
      cancers between groups was compared using the Fisher exact test. MAIN OUTCOME
      MEASURES: Frequency of germline methylation in PTEN mutation-negative Cowden
      syndrome and Cowden syndrome-like individuals. Prevalence of component cancers in
      methylation-positive and PTEN mutation-positive individuals. RESULTS: Of 123
      patients with Cowden syndrome or Cowden-like syndrome, 45 (37%; 95% confidence
      interval [CI], 29%-45%) showed hypermethylation upstream of PTEN but no
      transcriptional repression. The germline methylation was found to
      transcriptionally down-regulate KILLIN by 250-fold (95% CI, 45-14 286; P = .007)
      and exclusively disrupted TP53 activation of KILLIN by 30% (95% CI, 7%-45%; P =
      .008). Demethylation treatment increased only KILLIN expression 4.88-fold (95%
      CI, 1.4-18.1; P = .05). Individuals with KILLIN -promoter methylation had a 3
      fold increased prevalence of breast cancer (35/42 vs 24/64; P < .0001) and a
      greater than 2-fold increase of kidney cancer (4/45 vs 6/155; P = .004) over
      individuals with germline PTEN mutations. CONCLUSIONS: Germline KILLIN
      methylation is common among patients with Cowden syndrome or Cowden-like syndrome
      and is associated with increased risks of breast and renal cancer over PTEN
      mutation-positive individuals. These observations need to be replicated.

PMID- 21177509
TI  - When separate is more equal.

PMID- 21177510
TI  - Could physicians take the lead in health reform?

PMID- 21177511
TI  - The "shadow government" in health care.

PMID- 21177512
TI  - PTEN promoter silencing and Cowden syndrome: the role of epigenetic regulation of
      KILLIN.

PMID- 21177513
TI  - JAMA patient page. Acute myeloid leukemia.

PMID- 21177514
TI  - An integration of color and motion information in visual scene analyses.
AB  - To analyze complex scenes efficiently, the human visual system performs
      perceptual groupings based on various features (e.g., color and motion) of the
      visual elements in a scene. Although previous studies demonstrated that such
      groupings can be based on a single feature (e.g., either color or motion
      information), here we show that the visual system also performs scene analyses
      based on a combination of two features. We presented subjects with a mixture of
      red and green dots moving in various directions. Although the pairings between
      color and motion information were variable across the dots (e.g., one red dot
      moved upward while another moved rightward), subjects' perceptions of the color
      motion pairings were significantly biased when the randomly paired dots were
      flanked by additional dots with consistent color-motion pairings. These results
      indicate that the visual system resolves local ambiguities in color-motion
      pairings using unambiguous pairings in surrounds, demonstrating a new type of
      scene analysis based on the combination of two featural cues.

PMID- 21177515
TI  - Participating in politics resembles physical activity: general action patterns in
      international archives, United States archives, and experiments.
AB  - A series of studies examined whether political participation can emerge from
      general patterns of indiscriminate activity. In the first two studies, general
      action tendencies were measured by combining national and state-level indicators
      of high activity (e.g., impulsiveness, pace of life, and physical activity) from
      international and U.S. data. This action-tendency index positively correlated
      with a measure of political participation that consisted of voting behaviors and
      participation in political demonstrations. The following two experimental studies
      indicated that participants exposed to action words (e.g., go, move) had stronger
      intentions to vote in an upcoming election and volunteered more time to make
      phone calls on behalf of a university policy than participants exposed to
      inaction words did (e.g., relax, stop). These studies suggest that political
      participation can be predicted from general tendencies toward activity present at
      the national and state levels, as well as from verbal prompts suggestive of
      activity.

PMID- 21177516
TI  - Virtual reality versus computer-aided exposure treatments for fear of flying.
AB  - Evidence is growing that two modalities of computer-based exposure therapies-
      virtual reality and computer-aided psychotherapy--are effective in treating
      anxiety disorders, including fear of flying. However, they have not yet been
      directly compared. The aim of this study was to analyze the efficacy of three
      computer-based exposure treatments for fear of flying: virtual reality exposure
      therapy (VRET), computer-aided exposure with a therapist's (CAE-T) assistance
      throughout exposure sessions, and self-administered computer-aided exposure (CAE
      SA). A total of 60 participants with flying phobia were randomly assigned to
      VRET, CAE-T, or CAE-SA. Results indicate that the three interventions were
      effective in reducing fear of flying at posttreatment and at 1-year follow-up;
      furthermore, there were no significant differences between them in any of the
      outcome measure. Large within-group effect sizes were found for all three
      treatment conditions at both posttreatment and at follow-up. The results suggest
      that therapist involvement might be minimized during computer-based treatments
      and that CAE can be as effective as VRET in reducing fear of flying.

PMID- 21177517
TI  - A randomized controlled trial of acceptance-based behavior therapy and cognitive
      therapy for test anxiety: a pilot study.
AB  - Many university students suffer from test anxiety that is severe enough to impair
      performance. Given mixed efficacy results of previous cognitive-behavior therapy
      (CBT) trials and a theoretically driven rationale, an acceptance-based behavior
      therapy (ABBT) approach was compared to traditional CBT (i.e., Beckian cognitive
      therapy; CT) for the treatment of test anxiety. In this pilot study, 16
      university students with test anxiety were randomly assigned to receive either a
      CT or ABBT 2-hr group workshop. The two treatments produced markedly different
      effects on test performance (measured by exam scores), with those receiving ABBT
      experiencing improvements in performance, whereas those receiving CT exhibited
      reduced performance. In addition, there was a suggestion that ABBT might have
      been more effective at reducing subjectively experienced test anxiety (i.e., a
      nonsignificant but medium-sized group by time interaction effect). Implications
      of these results for the treatment of test anxiety and for theoretical notions
      related to cognitive change strategies are discussed.

PMID- 21177519
TI  - Brief experimental analysis of sight word interventions: a comparison of
      acquisition and maintenance of detected interventions.
AB  - The purpose of this study was to examine utility of a brief experimental analysis
      (BEA) in determining effective sight word interventions for a student with a
      history of difficulty with acquiring sight word recognition. Ten interventions
      were compared in a BEA. Following the BEA, an extended analysis was conducted
      that compared the two most effective interventions (from the BEA) with a control
      condition. Even though the BEA found two interventions to be relatively equal,
      one of the two interventions resulted in acquisition in half the sessions as the
      other intervention and this was replicated in a second extended analysis.
      Implications for BEA and recommendations for future research are discussed.

PMID- 21177518
TI  - Stress reduction at the work-family interface: positive parenting and self
      efficacy as mechanisms of change in Workplace Triple P.
AB  - Workplace Triple P (WPTP) is a group-based parenting skills training specifically
      designed to meet the needs of employed parents. Several randomized controlled
      trials have demonstrated the training's efficacy. This study examined possible
      mechanisms of change that account for the stress reduction effects of this
      parenting skills training at the work-family interface. It was hypothesized that
      reductions in dysfunctional parenting (DP) behavior and increases in parental
      self-efficacy would mediate the stress-reducing effects of WPTP. The mediator
      effects were analyzed in a German pre- and postcompleter sample (N = 97 parents;
      74 mothers and 23 fathers; treatment condition: n = 42 parents; waitlist-control
      condition n = 55 parents). The results indicate that individual stress- (IS)
      level reductions were mediated by decreased levels of DP. In addition, changes in
      IS levels mediated the effects of the training on work-related stress. The
      discussion focuses on the importance of understanding mechanisms of change to
      effectively implement interventions at the work-family interface.

PMID- 21177520
TI  - The effects of the good behavior game on the conduct of regular education new
      york city high school students.
AB  - The efficacy of the Good Behavior Game was examined in a multiethnic New York
      City public high school. Classroom rules were posted and students were divided
      into two teams. A reinforcement preference questionnaire was used to select daily
      and weekly prizes. The classroom teacher indicated that he was going to place a
      check on the board after every rule infraction as he named rule violators and
      their infractions. Students were also told that the team with the fewest marks at
      the end of each day would become the daily winners and receive prizes. They were
      also told that the team with the fewest marks for the week would be recognized as
      the weekly winners and receive additional prizes. The rate of disruptive behavior
      was charted across four treatment phases using a reversal design. The game phases
      were associated with marked reductions in the rate of seat leaving, talking
      without permission, and aggression. Teacher and student feedback supported the
      social validity of the procedure.

PMID- 21177521
TI  - Editorial report 2010.

PMID- 21177522
TI  - Kidney allograft survival: the long and short of it.

PMID- 21177523
TI  - What's new in hypertension 2010?

PMID- 21177526
TI  - Prevalence estimates for latent neurodegenerative disease.
AB  - Diseases that commonly cause dementia in the general population are Alzheimer's
      disease, microvascular brain injury, and Lewy body disease. Each of these is a
      chronic disease with latent, prodromal, and dementia stages. Here I present
      outcomes from validated neuropathologic assessments and cerebrospinal fluid
      biomarkers to estimate the prevalence of the latent stage of diseases that
      commonly contribute to the dementia syndrome. The latent stage of diseases that
      commonly cause dementia is highly prevalent in the adult population, highlighting
      the need for prevention strategies and longitudinal studies.

PMID- 21177528
TI  - A randomized study of a novel Zen dialogue method for producing spiritual and
      well-being enhancement: implications for end-of-life care.
AB  - OBJECTIVES: To test the hypothesis that a novel Zen dialogue-based method can
      bring about significant improvements in spiritual, meditation, and well-being
      parameters. DESIGN: A pretest-posttest design was used with participants being
      randomly assigned to either treatment or no treatment group at the Zen Center.
      The participants were 14 females and 2 males within each group with no prior
      formal Zen or meditation training. Those participants in the treatment group
      received intensive interaction for 1 day with an experienced Zen teacher using a
      dialogue method to induce a deep meditative state without instruction in formal
      meditation sitting practice. The outcome was measured with multiple previously
      standardized instruments designed to assess meditation states, well-being, and
      spirituality. RESULTS: A repeated-measures analysis of variance showed
      statistically significant differences between the treatment and control groups
      for all parameters measured. In addition, the meditative state measure suggested
      qualities consistent with deep meditation experiences. The results justify
      further investigation of the technique as a rapid spiritual intervention tool
      particularly for clients facing end-of-life issues.

PMID- 21177527
TI  - Proceedings of the 2010 National Toxicology Program Satellite Symposium.
AB  - The 2010 annual National Toxicology Program (NTP) Satellite Symposium, entitled
      "Pathology Potpourri," was held in Chicago, Illinois, in advance of the
      scientific symposium sponsored jointly by the Society of Toxicologic Pathology
      (STP) and the International Federation of Societies of Toxicologic Pathologists
      (IFSTP). The goal of the annual NTP Symposium is to present current diagnostic
      pathology or nomenclature issues to the toxicologic pathology community. This
      article presents summaries of the speakers' presentations, including diagnostic
      or nomenclature issues that were presented, along with select images that were
      used for voting or discussion. Some topics covered during the symposium included
      a comparison of rat and mouse hepatocholangiocarcinoma, a comparison of
      cholangiofibrosis and cholangiocarcinoma in rats, a mixed pancreatic neoplasm
      with acinar and islet cell components, an unusual preputial gland tumor, renal
      hyaline glomerulopathy in rats and mice, eosinophilic substance in the nasal
      septum of mice, INHAND nomenclature for proliferative and nonproliferative
      lesions of the CNS/PNS, retinal gliosis in a rat, fibroadnexal hamartoma in rats,
      intramural plaque in a mouse, a treatment-related chloracne-like lesion in mice,
      and an overview of mouse ovarian tumors.

PMID- 21177531
TI  - Elective single versus double embryo transfer.

PMID- 21177530
TI  - Clinical effectiveness of elective single versus double embryo transfer: meta
      analysis of individual patient data from randomised trials.
AB  - OBJECTIVE: To compare the effectiveness of elective single embryo transfer versus
      double embryo transfer on the outcomes of live birth, multiple live birth,
      miscarriage, preterm birth, term singleton birth, and low birth weight after
      fresh embryo transfer, and on the outcomes of cumulative live birth and multiple
      live birth after fresh and frozen embryo transfers. DESIGN: One stage meta
      analysis of individual patient data. DATA SOURCES: A systematic review of English
      and non-English articles from Medline, Embase, and the Cochrane Central Register
      of Controlled Trials (up to 2008). Additional studies were identified by contact
      with clinical experts and searches of bibliographies of all relevant primary
      articles. Search terms included embryo transfer, randomised controlled trial,
      controlled clinical trial, single embryo transfer, and double embryo transfer.
      Review methods Comparisons of the clinical effectiveness of cleavage stage (day 2
      or 3) elective single versus double embryo transfer after fresh or frozen in
      vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatments
      were included. Trials were included if the intervention differed only in terms of
      the intended number of embryos to be transferred. Trials that involved only
      blastocyst (day five) transfers were excluded. RESULTS: Individual patient data
      were received for every patient recruited to all eight eligible trials (n=1367).
      A total of 683 and 684 women randomised to the single and double embryo transfer
      arms, respectively, were included in the analysis. Baseline characteristics in
      the two groups were comparable. The overall live birth rate in a fresh IVF cycle
      was lower after single (181/683, 27%) than double embryo transfer (285/683, 42%)
      (adjusted odds ratio 0.50, 95% confidence interval 0.39 to 0.63), as was the
      multiple birth rate (3/181 (2%) v 84/285 (29%)) (0.04, 0.01 to 0.12). An
      additional frozen single embryo transfer, however, resulted in a cumulative live
      birth rate not significantly lower than the rate after one fresh double embryo
      transfer (132/350 (38%) v 149/353 (42%) (0.85, 0.62 to 1.15), with a minimal
      cumulative risk of multiple birth (1/132 (1%) v 47/149 (32%)). The odds of a term
      singleton birth (that is, over 37 weeks) after elective single embryo transfer
      was almost five times higher than the odds after double embryo transfer (4.93,
      2.98 to 8.18). CONCLUSIONS: Elective single embryo transfer results in a higher
      chance of delivering a term singleton live birth compared with double embryo
      transfer. Although this strategy yields a lower pregnancy rate than a double
      embryo transfer in a fresh IVF cycle, this difference is almost completely
      overcome by an additional frozen single embryo transfer cycle. The multiple
      pregnancy rate after elective single embryo transfer is comparable with that
      observed in spontaneous pregnancies.

PMID- 21177529
TI  - The cooperation of FGF receptor and Klotho is involved in excretory canal
      development and regulation of metabolic homeostasis in Caenorhabditis elegans.
AB  - FGFs have traditionally been associated with cell proliferation, morphogenesis,
      and development; yet, a subfamily of FGFs (FGF19, -21, and -23) functions as
      hormones to regulate glucose, lipid, phosphate, and vitamin D metabolism with
      impact on energy balance and aging. In mammals, Klotho and beta-Klotho are type 1
      transmembrane proteins that function as obligatory co-factors for endocrine FGFs
      to bind to their cognate FGF receptors (FGFRs). Mutations in Klotho/beta-Klotho
      or fgf19, -21, or -23 are associated with a number of human diseases, including
      autosomal dominant hypophosphatemic rickets, premature aging disorders, and
      diabetes. The Caenorhabditis elegans genome contains two paralogues of
      Klotho/beta-Klotho, klo-1, and klo-2. klo-1 is expressed in the C. elegans
      excretory canal, which is structurally and functionally paralogous to the
      vertebrate kidney. KLO-1 associates with EGL-15/FGFR, suggesting a role for KLO-1
      in the fluid homeostasis phenotype described previously for egl-15/fgfr mutants.
      Altered levels of EGL-15/FGFR signaling lead to defects in excretory canal
      development and function in C. elegans. These results suggest an evolutionarily
      conserved function for the FGFR-Klotho complex in the development of excretory
      organs such as the mammalian kidney and the worm excretory canal. These results
      also suggest an evolutionarily conserved function for the FGFR-Klotho axis in
      metabolic regulation.

PMID- 21177533
TI  - A transmembrane protein EIG121L is required for epidermal differentiation during
      early embryonic development.
AB  - Epidermal differentiation in the ventral ectoderm of Xenopus embryos is regulated
      by the bone morphogenetic protein (BMP) pathway. However, it remains unclear how
      the BMP pathway is activated and induces the epidermal fate in the ventral
      ectoderm. Here, we identify a novel player in the BMP pathway that is required
      for epidermal differentiation during Xenopus early embryonic development. We show
      that Xenopus EIG121L (xEIG121L) protein, an evolutionarily conserved
      transmembrane protein, is expressed in the ventral ectoderm at the gastrula and
      neurula stages. Almost complete knockdown of xEIG121L protein with antisense
      morpholino oligonucleotides in early Xenopus embryos results in severe
      developmental defects, including the inhibition of epidermal differentiation and
      the induction of neural genes. Remarkably, our analysis shows that BMP/Smad1
      signaling is severely suppressed in the xEIG121L knockdown ectoderm. Moreover,
      immunoprecipitation and immunostaining experiments suggest that xEIG121L protein
      physically interacts, and co-localizes, with BMP receptors. Thus, our results
      identify a novel regulator of the BMP pathway that has a positive role in BMP
      signaling and plays an essential role in epidermal differentiation during early
      embryonic development.

PMID- 21177535
TI  - Abnormal FDG-PET findings in particulate-induced lung disease.

PMID- 21177534
TI  - A novel KRAB domain-containing zinc finger transcription factor ZNF431 directly
      represses Patched1 transcription.
AB  - Kruppel-like zinc finger transcription factors compose the largest transcription
      factor family in the mammalian genome. However, the functions for the majority of
      these transcription factors as well as their in vivo downstream targets are not
      clear. We have functionally characterized a novel KRAB domain zinc finger
      transcription factor ZNF431 using both in vitro and in vivo assays. ZNF431 is a
      nuclear transcriptional repressor whose repressive activity depends on its
      association with HDAC1 and -2. Using the limb mesenchymal cell line MPLB, we
      identified Patched1 as a direct transcriptional target of ZNF431. Promoter
      analyses revealed three ZNF431 binding sites that bind to ZNF431 both in vitro
      and in vivo as revealed by gel-shift and chromatin immunoprecipitation,
      respectively. Mutations of these three sites abolished ZNF431 repression in
      transient transfection assays. Moreover, overexpressing ZNF431 in MPLB cells or
      in Xenopus and mouse embryos strongly repressed Patched1 expression. On the other
      hand, shRNA knockdown of ZNF431 in MPLB cells elevated Patched1 expression.
      Finally, hedgehog signaling readout was reduced in ZNF431 overexpression but
      elevated in ZNF431 knockdown MPLB cells. Our results indicate that ZNF431
      directly represses Patched1 expression and likely functions to repress the
      hedgehog response in cells.

PMID- 21177536
TI  - Emerging frontiers in healthcare research and delivery.: the 16th Annual HMO
      Research Network Conference, March 21-24, 2010, Austin, Texas.
AB  - The Health Maintenance Organization Research Network (HMORN), a consortium of 16
      healthcare delivery systems with integrated research centers, held their 16(th)
      annual conference in Austin, Texas from March 21-24, 2010. The conference was
      hosted by Scott & White Healthcare. Its theme "Emerging Frontiers in Healthcare
      Research and Delivery" reflected the objective of the conference which was to
      build synergy among scientists and clinicians to influence the health of the
      nation; to demonstrate the network's commitment to reach beyond traditional
      collaborators; discuss tools and technologies; and to expand opportunities for
      public-private partnerships in cutting-edge healthcare research and delivery.
      More than 320 researchers and healthcare professionals, representing each of the
      member HMOs, participated in this conference. Representatives from the AHRQ, CDC,
      NCI and NIH met with researchers to advance the quality and breadth of public
      domain research in HMOs. The objective of this article is to provide information
      about the HMORN and its 16(th) annual conference.

PMID- 21177635
TI  - Vibrio parahaemolyticus infection induces modulation of IL-8 secretion through
      dual pathway via VP1680 in Caco-2 cells.
AB  - BACKGROUND: Vibrio parahaemolyticus causes acute gastroenteritis and
      inflammations in humans. A variety of pathogenic bacteria can stimulate mitogen
      activated protein kinases (MAPKs) in host cells. Phosphorylation of MAPKs leads
      to production of interleukin (IL)- 8 and subsequently causes inflammations. Thus,
      MAPK cascades were strong candidates for the main signaling pathway of V.
      parahaemolyticus-induced acute inflammation. METHODS: To determine whether the
      signaling pathway on V. parahaemolyticus infection induces inflammation, we
      analyzed the secretion level of IL-8 and phosphorylation of MAPKs by use of
      intestinal epithelial Caco-2 cells. RESULTS: V. parahaemolyticus infection of
      Caco-2 cells activated extracellular signal-regulated kinase (ERK) 1/2 and p38
      MAPK signal pathways, leading to IL-8 secretion, whereas MAPK inhibitors, UO126
      or SB203580, suppressed IL-8 secretion. A strain carrying a deletion of VP1680, a
      type three secretion system 1 (T3SS1) effector protein, failed to activate
      phosphorylation of ERK1/2 and p38 MAPK and secretion of IL-8. ERK1/2 pathway
      inhibitor, UO126, failed IL-8 promoter activity, whereas p38 MAPK inhibitor,
      SB203580, decreased the stabilization of IL-8 messenger RNA following V.
      parahaemolyticus infection. CONCLUSIONS: We showed that V. parahaemolyticus
      infection of Caco-2 cells results in the secretion of IL-8, and that VP1680 plays
      a pivotal role in manipulating host cell signaling and is responsible for
      triggering IL-8 secretion.

PMID- 21177636
TI  - Hepcidin and iron species distribution inside the first-trimester human
      gestational sac.
AB  - We have investigated factors affecting iron distribution in the first-trimester
      gestational sac, by the measurement of transferrin, non-transferrin-bound iron
      (NTBI) and pro-hepcidin (Hep) in maternal serum, coelomic fluid (CF) and amniotic
      fluid (AF) and by immunostaining for Hep in villous and secondary yolk sac
      biopsies. These samples were obtained from 15 first-trimester pregnancies at 8-11
      weeks gestation. Transferrin concentrations were significantly lower in fetal
      (0.56 mg/ml) than maternal serum (1.71 mg/ml), with very low concentrations in CF
      and AF (0.09 mg/ml). In contrast, transferrin saturations were significantly
      higher in fetal (77%) than maternal serum (33%). NTBI was present in fetal serum,
      CF and AF, presumably as a consequence of low transferrin concentrations in these
      compartments. Pro-Hep was present at lower levels in fetal (140.0 +/- 11.1) than
      maternal serum (206.2 +/- 9.2) and at low concentrations in CF (19.4 +/- 3.1) and
      AF (21.8 +/- 5.2). Immunostaining with Hep antibody was found in the
      syncytiotrophoblast of first-trimester placenta as well as in mesothelial and
      endodermal layers of the secondary yolk sac at 10 weeks. The presence of Hep in
      syncytiotrophoblast cells of first-trimester placenta as well as in mesothelial
      and endodermal layers of the secondary yolk sac suggest a key regulatory role for
      this protein in iron transfer to the first-trimester fetus. The low transferrin
      concentrations and the presence of NTBI in CF and AF suggest that transferrin
      independent iron transfer is important in early gestation.

PMID- 21177637
TI  - Expression of milk fat globule EGF-factor 8 (MFG-E8) mRNA and protein in the
      human endometrium and its regulation by prolactin.
AB  - Milk fat globule epidermal growth-factor 8 (MFG-E8) has not been previously
      linked to endometrial physiology. We reported on MFG-E8 mRNA up-regulation in the
      human endometrium during the window of implantation (WOI) using microarrays.
      Prolactin (PRL) secreted by stromal cells has been suggested to modulate protein
      expression. The objective of this study was to characterize the endometrial
      expression of MFG-E8 and its ligand alphavbeta3 integrin during the menstrual
      cycle and its possible regulation by PRL. MFG-E8 mRNA (real-time RT-PCR) and
      protein expression (immunohistochemistry and immunoblotting) were analyzed in
      human endometrial biopsies at different times of the menstrual cycle, as well as
      in primary endometrial cell cultures. In primary cultures of epithelial cells,
      MFG-E8 intracellular protein expression was evaluated in absence or presence of
      PRL (0.2 and 1 MUg/ml). The results show that MFG-E8 protein is almost
      exclusively localized to the epithelium in whole endometrial biopsies. Both MFG
      E8 mRNA and protein expression increased in the luteal phase and were highest
      during the WOI; epithelial protein location of alphavbeta3 integrin also peaked
      on cycle Day 24. Cultured epithelial cells showed a diffuse staining of MFG-E8
      over the cytoplasmic area; however, some cells presented a punctuated staining
      pattern. PRL treatment of epithelial cells for 72 h in vitro significantly
      increased MFG-E8 protein intracellular expression. This is the first report on
      MFG-E8 protein localization to the human endometrial epithelium and its up
      regulation during the WOI. The pattern of glandular expression of its ligand
      alphavbeta3 integrin was remarkably similar. In vitro data support a modulatory
      role for PRL as a stromal/epithelial paracrine factor controlling MFG-E8.

PMID- 21177639
TI  - Levels of evidence: further insight on Gugiu and Gugiu.

PMID- 21177640
TI  - Clinical guidelines and practice: a commentary on the complexity of tinnitus
      management.
AB  - Subjective tinnitus is an enigmatic and chronic condition that is predominantly
      managed as symptomatic. Little high-level evidence exists for the efficacy and
      specificity of the various tinnitus management strategies currently used, and
      this is reflected in documents that aim to guide clinicians. As a consequence,
      there are clear gaps in evidence-based practice linking diagnosis to the most
      effective management strategies as well as a general lack of consensus about
      which are appropriate strategies for assessment and management. Several
      guidelines have been produced from research efforts and from expert opinion. All
      recommend standardization of assessment and a range of management options but do
      not yet provide a means to link the two. The authors call for clinicians,
      scientists, and policy makers to work together to address this barrier to good
      practice.

PMID- 21177641
TI  - Physicians, guidelines, and cognitive tasks.
AB  - Using a case study analysis of the Expert Panel Report 3 (EPR-3): Guidelines for
      the Diagnosis and Treatment of Asthma, this article compares the workflows and
      knowledge requirements of primary care practice to the structure and content of a
      well-respected set of clinical guidelines. The authors show that there are
      discrepancies between physician workflow and the structure of the EPR-3, as well
      as between physicians' knowledge requirements and the content of the EPR-3. The
      analysis suggests that closing the gap between medical knowledge and practice
      will require alternative ways to represent guidelines' knowledge and
      recommendations.

PMID- 21177642
TI  - Two groups of phenylalanine biosynthetic operon leader peptides genes: a high
      level of apparently incidental frameshifting in decoding Escherichia coli pheL.
AB  - The bacterial pheL gene encodes the leader peptide for the phenylalanine
      biosynthetic operon. Translation of pheL mRNA controls transcription attenuation
      and, consequently, expression of the downstream pheA gene. Fifty-three unique
      pheL genes have been identified in sequenced genomes of the gamma subdivision.
      There are two groups of pheL genes, both of which are short and contain a run(s)
      of phenylalanine codons at an internal position. One group is somewhat diverse
      and features different termination and 5'-flanking codons. The other group,
      mostly restricted to Enterobacteria and including Escherichia coli pheL, has a
      conserved nucleotide sequence that ends with UUC_CCC_UGA. When these three codons
      in E. coli pheL mRNA are in the ribosomal E-, P- and A-sites, there is an
      unusually high level, 15%, of +1 ribosomal frameshifting due to features of the
      nascent peptide sequence that include the penultimate phenylalanine. This level
      increases to 60% with a natural, heterologous, nascent peptide stimulator.
      Nevertheless, studies with different tRNA(Pro) mutants in Salmonella enterica
      suggest that frameshifting at the end of pheL does not influence expression of
      the downstream pheA. This finding of incidental, rather than utilized,
      frameshifting is cautionary for other studies of programmed frameshifting.

PMID- 21177643
TI  - GiRaF: robust, computational identification of influenza reassortments via graph
      mining.
AB  - Reassortments in the influenza virus--a process where strains exchange genetic
      segments--have been implicated in two out of three pandemics of the 20th century
      as well as the 2009 H1N1 outbreak. While advances in sequencing have led to an
      explosion in the number of whole-genome sequences that are available, an
      understanding of the rate and distribution of reassortments and their role in
      viral evolution is still lacking. An important factor in this is the paucity of
      automated tools for confident identification of reassortments from sequence data
      due to the challenges of analyzing large, uncertain viral phylogenies. We
      describe here a novel computational method, called GiRaF (Graph-incompatibility
      based Reassortment Finder), that robustly identifies reassortments in a fully
      automated fashion while accounting for uncertainties in the inferred phylogenies.
      The algorithms behind GiRaF search large collections of Markov chain Monte Carlo
      (MCMC)-sampled trees for groups of incompatible splits using a fast biclique
      enumeration algorithm coupled with several statistical tests to identify sets of
      taxa with differential phylogenetic placement. GiRaF correctly finds known
      reassortments in human, avian, and swine influenza populations, including the
      evolutionary events that led to the recent 'swine flu' outbreak. GiRaF also
      identifies several previously unreported reassortments via whole-genome studies
      to catalog events in H5N1 and swine influenza isolates.

PMID- 21177644
TI  - T-lex: a program for fast and accurate assessment of transposable element
      presence using next-generation sequencing data.
AB  - Transposable elements (TEs) are repetitive DNA sequences that are ubiquitous,
      extremely abundant and dynamic components of practically all genomes. Much effort
      has gone into annotation of TE copies in reference genomes. The sequencing cost
      reduction and the newly available next-generation sequencing (NGS) data from
      multiple strains within a species offer an unprecedented opportunity to study
      population genomics of TEs in a range of organisms. Here, we present a
      computational pipeline (T-lex) that uses NGS data to detect the presence/absence
      of annotated TE copies. T-lex can use data from a large number of strains and
      returns estimates of population frequencies of individual TE insertions in a
      reasonable time. We experimentally validated the accuracy of T-lex detecting
      presence or absence of 768 previously identified TE copies in two resequenced
      Drosophila melanogaster strains. Approximately 95% of the TE insertions were
      detected with 100% sensitivity and 97% specificity. We show that even at low
      levels of coverage T-lex produces accurate results for TE copies that it can
      identify reliably but that the rate of 'no data' calls increases as the coverage
      falls below 15*. T-lex is a broadly applicable and flexible tool that can be used
      in any genome provided the availability of the reference genome, individual TE
      copy annotation and NGS data.

PMID- 21177645
TI  - seqMINER: an integrated ChIP-seq data interpretation platform.
AB  - In a single experiment, chromatin immunoprecipitation combined with high
      throughput sequencing (ChIP-seq) provides genome-wide information about a given
      covalent histone modification or transcription factor occupancy. However, time
      efficient bioinformatics resources for extracting biological meaning out of these
      gigabyte-scale datasets are often a limiting factor for data interpretation by
      biologists. We created an integrated portable ChIP-seq data interpretation
      platform called seqMINER, with optimized performances for efficient handling of
      multiple genome-wide datasets. seqMINER allows comparison and integration of
      multiple ChIP-seq datasets and extraction of qualitative as well as quantitative
      information. seqMINER can handle the biological complexity of most experimental
      situations and proposes methods to the user for data classification according to
      the analysed features. In addition, through multiple graphical representations,
      seqMINER allows visualization and modelling of general as well as specific
      patterns in a given dataset. To demonstrate the efficiency of seqMINER, we have
      carried out a comprehensive analysis of genome-wide chromatin modification data
      in mouse embryonic stem cells to understand the global epigenetic landscape and
      its change through cellular differentiation.

PMID- 21177646
TI  - Arxes: retrotransposed genes required for adipogenesis.
AB  - Retrotransposed sequences arise from messenger RNAs (mRNAs) that have been
      reinserted into genomic DNA by reverse transcription. Usually, these sequences
      are embedded in dormant regions, collect missense mutations over time and
      constitute processed, nonfunctional pseudogenes. There are thousands of processed
      pseudogenes in the mouse and human genome. Here, we report evidence for two
      paralog genes (termed Arxes1 and Arxes2), which arose by retrotransposition of
      the signal peptidase Spcs3 followed by a segmental duplication event. They gained
      a functional promoter that we show to be transactivated by adipogenic
      transcription factors. We further show that the Arxes mRNAs are highly expressed
      in adipose tissue and strongly upregulated during adipogenesis in different cell
      models. Additionally, their expression is elevated by an anti-diabetic agent in
      vitro and in vivo. Importantly, we provide evidence that the Arxes genes are
      translated and that the proteins are located in the endoplasmic reticulum.
      Although the sequence similarity and subcellular location are reminiscent of
      their parental gene, our data suggest that the Arxes have developed a different
      function, since their expression is required for adipogenesis, whereas Spcs3 is
      dispensable. In summary, we report retrotransposed-duplicated genes that evolved
      from a parental gene to function in a tissue and adipogenesis-specific context.

PMID- 21177647
TI  - Nucleosome accessibility governed by the dimer/tetramer interface.
AB  - Nucleosomes are multi-component macromolecular assemblies which present a
      formidable obstacle to enzymatic activities that require access to the DNA, e.g.
      DNA and RNA polymerases. The mechanism and pathway(s) by which nucleosomes
      disassemble to allow DNA access are not well understood. Here we present evidence
      from single molecule FRET experiments for a previously uncharacterized
      intermediate structural state before H2A-H2B dimer release, which is
      characterized by an increased distance between H2B and the nucleosomal dyad. This
      suggests that the first step in nucleosome disassembly is the opening of the (H3
      H4)(2) tetramer/(H2A-H2B) dimer interface, followed by H2A-H2B dimer release from
      the DNA and, lastly, (H3-H4)(2) tetramer removal. We estimate that the open
      intermediate state is populated at 0.2-3% under physiological conditions. This
      finding could have significant in vivo implications for factor-mediated histone
      removal and exchange, as well as for regulating DNA accessibility to the
      transcription and replication machinery.

PMID- 21177649
TI  - Fox-3 and PSF interact to activate neural cell-specific alternative splicing.
AB  - Fox-1 family (Fox) proteins, which consist of Fox-1 (A2BP1), Fox-2 (Rbm9) and Fox
      3 (NeuN) in mammals, bind to the RNA element UGCAUG and regulate alternative pre
      mRNA splicing. However the mechanisms for Fox-regulated splicing are largely
      unknown. We analyzed the expression pattern of the three Fox proteins as well as
      neural cell-specific alternative splicing of a cassette exon N30 of nonmuscle
      myosin heavy chain (NMHC) II-B in the mouse central nervous system. Histological
      and biochemical analyses following fluorescence-activated cell sorting
      demonstrate a positive correlation of N30 inclusion and Fox-3 expression.
      Further, we identified polypyrimidine tract binding protein-associated splicing
      factor (PSF) as an interacting protein with Fox-3 by affinity-chromatography. In
      cultured cells, enhancement of N30 inclusion by Fox-3 depends on the presence of
      PSF. PSF enhances N30 inclusion in a UGCAUG-dependent manner, although it does
      not bind directly to this element. Fox-3 is recruited to the UGCAUG element
      downstream of N30 in the endogenous NMHC II-B transcript in a PSF-dependent
      manner. This study is the first to identify PSF as a coactivator of Fox proteins
      and provides evidence that the Fox-3 and PSF interaction is an integral part of
      the mechanism by which Fox proteins regulate activation of alternative exons via
      a downstream intronic enhancer.

PMID- 21177648
TI  - Stability of telomeric G-quadruplexes.
AB  - In most eukaryotes, telomeric DNA consists of repeats of a short motif that
      includes consecutive guanines and may hence fold into G-quadruplexes. Budding
      yeasts have telomeres composed of longer repeats and show variation in the degree
      of repeat homogeneity. Although telomeric sequences from several organisms have
      been shown to fold into G-quadruplexes in vitro, surprisingly, no study has been
      dedicated to the comparison of G-quadruplex folding and stability of known
      telomeric sequences. Furthermore, to our knowledge, folding of yeast telomeric
      sequences into intramolecular G-quadruplexes has never been investigated. Using
      biophysical and biochemical methods, we studied sequences mimicking about four
      repetitions of telomeric motifs from a variety of organisms, including yeasts,
      with the aim of comparing the G-quadruplex folding potential of telomeric
      sequences among eukaryotes. G-quadruplex folding did not appear to be a conserved
      feature among yeast telomeric sequences. By contrast, all known telomeric
      sequences from eukaryotes other than yeasts folded into G-quadruplexes.
      Nevertheless, while G(3)T(1-4)A repeats (found in a variety of organisms) and
      G(4)T(2,4) repeats (found in ciliates) folded into stable G-quadruplexes, G
      quadruplexes formed by repetitions of G(2)T(2)A and G(2)CT(2)A motifs (found in
      many insects and in nematodes, respectively) appeared to be in equilibrium with
      non-G-quadruplex structures (likely hairpin-duplexes).

PMID- 21177650
TI  - Formation of stress-specific p53 binding patterns is influenced by chromatin but
      not by modulation of p53 binding affinity to response elements.
AB  - The p53 protein is crucial for adapting programs of gene expression in response
      to stress. Recently, we revealed that this occurs partly through the formation of
      stress-specific p53 binding patterns. However, the mechanisms that generate these
      binding patterns remain largely unknown. It is not established whether the
      selective binding of p53 is achieved through modulation of its binding affinity
      to certain response elements (REs) or via a chromatin-dependent mechanism. To
      shed light on this issue, we used a microsphere assay for protein-DNA binding to
      measure p53 binding patterns on naked DNA. In parallel, we measured p53 binding
      patterns within chromatin using chromatin immunoprecipitation and DNase I coupled
      to ligation-mediated polymerase chain reaction footprinting. Through this
      experimental approach, we revealed that UVB and Nutlin-3 doses, which lead to
      different cellular outcomes, induce similar p53 binding patterns on naked DNA.
      Conversely, the same treatments lead to stress-specific p53 binding patterns on
      chromatin. We show further that altering chromatin remodeling using an histone
      acetyltransferase inhibitor reduces p53 binding to REs. Altogether, our results
      reveal that the formation of p53 binding patterns is not due to the modulation of
      sequence-specific p53 binding affinity. Rather, we propose that chromatin and
      chromatin remodeling are required in this process.

PMID- 21177651
TI  - Transition dynamics and selection of the distinct S-DNA and strand unpeeling
      modes of double helix overstretching.
AB  - Recent studies have revealed two distinct pathways for the DNA overstretching
      transition near 65 pN: 'unpeeling' of one strand from the other, and a transition
      from B-DNA to an elongated double-stranded 'S-DNA' form. However, basic questions
      concerning the dynamics of these transitions, relative stability of the two
      competing overstretched states, and effects of nicks and free DNA ends on
      overstretching, remain open. In this study we report that: (i) stepwise extension
      changes caused by sequence-defined barriers occur during the strand-unpeeling
      transition, whereas rapid, sequence-independent extension fluctuations occur
      during the B to S transition; (ii) the secondary transition that often occurs
      following the overstretching transition is strand-unpeeling, during which the
      extension increases by 0.01-0.02 nm per base pair of S-DNA converted to single
      stranded DNA at forces between 75 and 110 pN; (iii) even in the presence of nicks
      or free ends, S-DNA can be stable under physiological solution conditions; (iv)
      distribution of small GC-rich islands in a large DNA plays a key role in
      determining the transition pathways; and (v) in the absence of nicks or free
      ends, torsion-unconstrained DNA undergoes the overstretching transition via
      creation of S-DNA. Our study provides a new, high-resolution understanding of the
      competition between unpeeling and formation of S-DNA.

PMID- 21177652
TI  - The chromodomains of CHD1 are critical for enzymatic activity but less important
      for chromatin localization.
AB  - The molecular motor protein CHD1 has been implicated in the regulation of
      transcription and in the transcription-independent genome-wide incorporation of
      H3.3 into paternal chromatin in Drosophila melanogaster. A key feature of CHD1 is
      the presence of two chromodomains, which can bind to histone H3 methylated at
      lysine 4 and thus might serve to recruit and/or maintain CHD1 at the chromatin.
      Here, we describe genetic and biochemical approaches to the study of the
      Drosophila CHD1 chromodomains. We found that overall localization of CHD1 on
      polytene chromosomes does not appreciably change in chromodomain-mutant flies. In
      contrast, the chromodomains are important for transcription-independent
      activities of CHD1 during early embryonic development as well as for
      transcriptional regulation of several heat shock genes. However, neither CHD1 nor
      its chromodomains are needed for RNA polymerase II localization and H3K4
      methylation but loss of CHD1 decreases transcription-induced histone eviction at
      the Hsp70 gene in vivo. Chromodomain mutations negatively affect the chromatin
      assembly activities of CHD1 in vitro, and they appear to be involved in linking
      the ATP-dependent motor to the chromatin assembly function of CHD1.

PMID- 21177653
TI  - c-MYC coordinately regulates ribosomal gene chromatin remodeling and Pol I
      availability during granulocyte differentiation.
AB  - Loss of c-MYC is required for downregulation of ribosomal RNA (rRNA) gene (rDNA)
      transcription by RNA Polymerase I (Pol I) during granulocyte differentiation.
      Here, we demonstrate a robust reduction of Pol I loading onto rDNA that along
      with a depletion of the MYC target gene upstream binding factor (UBF) and a
      switch from epigenetically active to silent rDNA accompanies this MYC reduction.
      We hypothesized that MYC may coordinate these mechanisms via direct regulation of
      multiple components of the Pol I transcription apparatus. Using gene expression
      arrays we identified a 'regulon' of Pol I factors that are both downregulated
      during differentiation and reinduced in differentiated granulocytes upon
      activation of the MYC-ER transgene. This regulon includes the novel c-MYC target
      genes RRN3 and POLR1B. Although enforced MYC expression during granulocyte
      differentiation was sufficient to increase the number of active rRNA genes, its
      activation in terminally differentiated cells did not alter the active to
      inactive gene ratio despite increased rDNA transcription. Thus, c-MYC dynamically
      controls rDNA transcription during granulocytic differentiation through the
      orchestrated transcriptional regulation of core Pol I factors and epigenetic
      modulation of number of active rRNA genes.

PMID- 21177654
TI  - Genome-wide evidence for an essential role of the human Staf/ZNF143 transcription
      factor in bidirectional transcription.
AB  - In the human genome, ~ 10% of the genes are arranged head to head so that their
      transcription start sites reside within <1 kbp on opposite strands. In this
      configuration, a bidirectional promoter generally drives expression of the two
      genes. How bidirectional expression is performed from these particular promoters
      constitutes a puzzling question. Here, by a combination of in silico and
      biochemical approaches, we demonstrate that hStaf/ZNF143 is involved in
      controlling expression from a subset of divergent gene pairs. The binding sites
      for hStaf/ZNF143 (SBS) are overrepresented in bidirectional versus unidirectional
      promoters. Chromatin immunoprecipitation assays with a significant set of
      bidirectional promoters containing putative SBS revealed that 93% of them are
      associated with hStaf/ZNF143. Expression of dual reporter genes directed by
      bidirectional promoters are dependent on the SBS integrity and requires
      hStaf/ZNF143. Furthermore, in some cases, functional SBS are located in
      bidirectional promoters of gene pairs encoding a noncoding RNA and a protein
      gene. Remarkably, hStaf/ZNF143 per se exhibits an inherently bidirectional
      transcription activity, and together our data provide the demonstration that
      hStaf/ZNF143 is indeed a transcription factor controlling the expression of
      divergent protein-protein and protein-non-coding RNA gene pairs.

PMID- 21177655
TI  - The 2011 Nucleic Acids Research Database Issue and the online Molecular Biology
      Database Collection.
AB  - The current 18th Database Issue of Nucleic Acids Research features descriptions
      of 96 new and 83 updated online databases covering various areas of molecular
      biology. It includes two editorials, one that discusses COMBREX, a new exciting
      project aimed at figuring out the functions of the 'conserved hypothetical'
      proteins, and one concerning BioDBcore, a proposed description of the 'minimal
      information about a biological database'. Papers from the members of the
      International Nucleotide Sequence Database collaboration (INSDC) describe each of
      the participating databases, DDBJ, ENA and GenBank, principles of data exchange
      within the collaboration, and the recently established Sequence Read Archive. A
      testament to the longevity of databases, this issue includes updates on the RNA
      modification database, Definition of Secondary Structure of Proteins (DSSP) and
      Homology-derived Secondary Structure of Proteins (HSSP) databases, which have not
      been featured here in >12 years. There is also a block of papers describing
      recent progress in protein structure databases, such as Protein DataBank (PDB),
      PDB in Europe (PDBe), CATH, SUPERFAMILY and others, as well as databases on
      protein structure modeling, protein-protein interactions and the organization of
      inter-protein contact sites. Other highlights include updates of the popular gene
      expression databases, GEO and ArrayExpress, several cancer gene databases and a
      detailed description of the UK PubMed Central project. The Nucleic Acids Research
      online Database Collection, available at:
      http://www.oxfordjournals.org/nar/database/a/, now lists 1330 carefully selected
      molecular biology databases. The full content of the Database Issue is freely
      available online at the Nucleic Acids Research web site
      (http://nar.oxfordjournals.org/).

PMID- 21177656
TI  - The Gene Expression Barcode: leveraging public data repositories to begin
      cataloging the human and murine transcriptomes.
AB  - Various databases have harnessed the wealth of publicly available microarray data
      to address biological questions ranging from across-tissue differential
      expression to homologous gene expression. Despite their practical value, these
      databases rely on relative measures of expression and are unable to address the
      most fundamental question--which genes are expressed in a given cell type. The
      Gene Expression Barcode is the first database to provide reliable absolute
      measures of expression for most annotated genes for 131 human and 89 mouse tissue
      types, including diseased tissue. This is made possible by a novel algorithm that
      leverages information from the GEO and ArrayExpress public repositories to build
      statistical models that permit converting data from a single microarray into
      expressed/unexpressed calls for each gene. For selected platforms, users may
      upload data and obtain results in a matter of seconds. The raw data, curated
      annotation, and code used to create our resource are also available at
      http://rafalab.jhsph.edu/barcode.

PMID- 21177657
TI  - mESAdb: microRNA expression and sequence analysis database.
AB  - microRNA expression and sequence analysis database
      (http://konulab.fen.bilkent.edu.tr/mirna/) (mESAdb) is a regularly updated
      database for the multivariate analysis of sequences and expression of microRNAs
      from multiple taxa. mESAdb is modular and has a user interface implemented in PHP
      and JavaScript and coupled with statistical analysis and visualization packages
      written for the R language. The database primarily comprises mature microRNA
      sequences and their target data, along with selected human, mouse and zebrafish
      expression data sets. mESAdb analysis modules allow (i) mining of microRNA
      expression data sets for subsets of microRNAs selected manually or by motif; (ii)
      pair-wise multivariate analysis of expression data sets within and between taxa;
      and (iii) association of microRNA subsets with annotation databases, HUGE
      Navigator, KEGG and GO. The use of existing and customized R packages facilitates
      future addition of data sets and analysis tools. Furthermore, the ability to
      upload and analyze user-specified data sets makes mESAdb an interactive and
      expandable analysis tool for microRNA sequence and expression data.

PMID- 21177658
TI  - IsoBase: a database of functionally related proteins across PPI networks.
AB  - We describe IsoBase, a database identifying functionally related proteins, across
      five major eukaryotic model organisms: Saccharomyces cerevisiae, Drosophila
      melanogaster, Caenorhabditis elegans, Mus musculus and Homo Sapiens. Nearly all
      existing algorithms for orthology detection are based on sequence comparison.
      Although these have been successful in orthology prediction to some extent, we
      seek to go beyond these methods by the integration of sequence data and protein
      protein interaction (PPI) networks to help in identifying true functionally
      related proteins. With that motivation, we introduce IsoBase, the first publicly
      available ortholog database that focuses on functionally related proteins. The
      groupings were computed using the IsoRankN algorithm that uses spectral methods
      to combine sequence and PPI data and produce clusters of functionally related
      proteins. These clusters compare favorably with those from existing approaches:
      proteins within an IsoBase cluster are more likely to share similar Gene Ontology
      (GO) annotation. A total of 48,120 proteins were clustered into 12,693
      functionally related groups. The IsoBase database may be browsed for functionally
      related proteins across two or more species and may also be queried by accession
      numbers, species-specific identifiers, gene name or keyword. The database is
      freely available for download at http://isobase.csail.mit.edu/.

PMID- 21177659
TI  - TMPad: an integrated structural database for helix-packing folds in transmembrane
      proteins.
AB  - alpha-helical transmembrane (TM) proteins play an important role in many critical
      and diverse biological processes, and specific associations between TM helices
      are important determinants for membrane protein folding, dynamics and function.
      In order to gain insights into the above phenomena, it is necessary to
      investigate different types of helix-packing modes and interactions. However,
      such information is difficult to obtain because of the experimental impediment
      and a lack of a well-annotated source of helix-packing folds in TM proteins. We
      have developed the TMPad (TransMembrane Protein Helix-Packing Database) which
      addresses the above issues by integrating experimentally observed helix-helix
      interactions and related structural information of membrane proteins.
      Specifically, the TMPad offers pre-calculated geometric descriptors at the helix
      packing interface including residue backbone/side-chain contacts, interhelical
      distances and crossing angles, helical translational shifts and rotational
      angles. The TMPad also includes the corresponding sequence, topology, lipid
      accessibility, ligand-binding information and supports structural classification,
      schematic diagrams and visualization of the above structural features of TM helix
      packing. Through detailed annotations and visualizations of helix-packing, this
      online resource can serve as an information gateway for deciphering the
      relationship between helix-helix interactions and higher levels of organization
      in TM protein structure and function. The website of the TMPad is freely
      accessible to the public at http://bio-cluster.iis.sinica.edu.tw/TMPad.

PMID- 21177660
TI  - Endogenous testosterone and cardiovascular disease in healthy men: a meta
      analysis.
AB  - CONTEXT: The literature provides no clear answer as to whether low endogenous
      testosterone increases risk of cardiovascular disease (CVD) in healthy men.
      OBJECTIVE: Our purpose was to estimate the predictive value of testosterone for
      CVD and to identify study features explaining conflicting results. DATA SOURCES:
      Articles were identified by a Medline and Embase search and citation tracking.
      STUDY SELECTION: Eligible were prospective population-based cohort and nested
      case-control studies of testosterone and atherosclerosis, stroke, myocardial
      infarction, ischaemic heart disease, death from coronary heart disease or
      mortality. DATA EXTRACTION: Two independent researchers re-expressed associations
      of testosterone and CVD in a uniform manner to be used in meta-regression
      analyses for identification of study features explaining conflicting results, and
      to estimate the predictive value of testosterone for CVD. RESULTS AND
      CONCLUSIONS: 19 potentially eligible articles were identified. Overall, a weak
      independent association was found with an estimated summary RR of 0.89 for a
      change of one standard deviation in total testosterone level (95% CI 0.83 to
      0.96). Age of study population and year of publication modified the relationship
      between testosterone and CVD. The estimated summary RR was 1.01 (0.95 to 1.08)
      for studies of men younger than 70 years of age, and 0.84 (0.76 to 0.92) for
      studies including men over 70 years of age. The latter studies showed a
      particular pronounced association if published after 1 January 2007. Results were
      largely confirmed by separate analyses of free- and bioavailable testosterone.
      The systematic review displayed no association between endogenous testosterone
      and risk for CVD in middle-aged men. In elderly men, testosterone may weakly
      protect against CVD. Alternatively, low testosterone may indicate a poor general
      health.

PMID- 21177661
TI  - Participatory ergonomics to reduce exposure to psychosocial and physical risk
      factors for low back pain and neck pain: results of a cluster randomised
      controlled trial.
AB  - OBJECTIVES: This study investigated the effectiveness of the Stay@Work
      participatory ergonomics programme to reduce workers' exposure to psychosocial
      and physical risk factors. METHODS: 37 departments (n=3047 workers) from four
      Dutch companies participated in this cluster randomised controlled trial; 19
      (n=1472 workers) were randomised to an intervention group (participatory
      ergonomics) and 18 (n=1575 workers) to a control group (no participatory
      ergonomics). During a 6 h meeting guided by an ergonomist, working groups devised
      ergonomic measures to reduce psychosocial and physical workload and implemented
      them within 3months in their departments. Data on psychosocial and physical risk
      factors for low back pain and neck pain were collected at baseline and after 6
      months. Psychosocial risk factors were measured using the Job Content
      Questionnaire and physical risk factors using the Dutch Musculoskeletal
      Questionnaire. Intervention effects were studied using multilevel analysis.
      RESULTS: Intervention group workers significantly increased on decision latitude
      (0.29 points; 95% CI 0.07 to 0.52) and decision authority (0.16 points; 95% CI
      0.04 to 0.28) compared to control workers. However, exposure to awkward trunk
      working postures significantly increased in the intervention group (OR 1.86; 95%
      CI 1.15 to 3.01) compared to the control group. No significant differences
      between the intervention and control group were found for the remaining risk
      factors. After 6months, loss to follow-up was 35% in the intervention group and
      29% in the control group. CONCLUSION: Participatory ergonomics was not effective
      in reducing exposure to psychosocial and physical risk factors for low back pain
      and neck pain among a large group of workers. TRIAL REGISTRATION: ISRCTN27472278.

PMID- 21177662
TI  - Strategic responses to intimate partner violence against women in Spain: a
      national study in primary care.
AB  - BACKGROUND: Research on women''s responses to intimate partner violence (IPV) has
      largely been limited to women who have been exposed to severe physical violence
      with scarce generalisation. This study aimed to analyse how Spanish abused women
      from different backgrounds and with different IPV characteristics respond to
      violence. METHOD: Women experiencing IPV before the previous year (1469) were
      selected from a large cross-sectional national survey of adult women recruited
      during 2006-7 among female patients seeking medical care for whatever reason in
      primary healthcare services. The outcome variables were women's responses to IPV
      and the predictor variables were personal and social resources profiles and
      characteristics of the abuse (type, duration and women's age at onset). Stepwise
      logistic regression models were fitted. RESULTS: 87.5% of abused women took some
      kind of action to overcome IPV. Significant differences on personal and social
      profile and type and duration of the abuse were detected between the three
      strategic responses: distancing, in process and inhibition. The probability of a
      woman responding with a distancing strategy (seeking outside help or leaving
      temporarily) is almost three times greater if she is employed, was young when the
      abuse began, had experienced physical and psychological abuse and when the abuse
      was under 5 years. CONCLUSIONS: The results of this study show that personal and
      social resources and the specific circumstances of the abuse should be taken into
      account to understand women's responses to IPV. Well-validated interventions
      targeted at abused women's needs and the circumstances of IPV remain a priority.

PMID- 21177663
TI  - Are negative aspects of social relations predictive of angina pectoris? A 6-year
      follow-up study of middle-aged Danish women and men.
AB  - BACKGROUND: Social relations have been shown to be protective against ischaemic
      heart disease (IHD), but little is known about the impact of negative aspects of
      the social relations on IHD. METHODS: During a 6-year follow-up, the authors
      aimed to assess if negative aspects of social relations were associated with
      angina pectoris among 4573 middle-aged Danish men and women free of heart disease
      at baseline in 2000. RESULTS: Nine per cent experienced onset of symptoms of
      angina pectoris. A higher degree of excessive demands or worries from the social
      relations was associated with increased risk of angina after adjustment for age,
      gender, social class, cohabitation status and depression in a dose-response
      manner. For example, experiencing excessive demands or worries always/often from
      different roles in the social relations was associated with an increased risk:
      partner OR=3.53 (1.68 to 7.43), children OR=2.19 (1.04 to 4.61), other family
      OR=1.91 (1.24 to 2.96). Except for frequent conflicts with the partner and
      neighbours, conflicts with the social relations was not a risk factor for angina.
      The authors found no interaction of negative aspects of social relations with
      gender, age, social class, cohabitation status or depression in terms of angina.
      CONCLUSION: Excessive demands and serious worries from significant others seem to
      be important risk factors for development of angina pectoris.

PMID- 21177664
TI  - Effectiveness and cost-effectiveness of an injury prevention programme for adult
      male amateur soccer players: design of a cluster-randomised controlled trial.
AB  - BACKGROUND AND AIMS: Approximately 16% of all sports injuries in the Netherlands
      are caused by outdoor soccer. A cluster-randomised controlled trial has been
      designed to investigate the effectiveness and cost-effectiveness of an injury
      prevention programme ('The11') for male amateur soccer players. The injury
      prevention programme The11, developed with the support of the World Football
      Association FIFA, aims to reduce the impact of intrinsic injury risk factors in
      soccer. METHODS: Teams playing at first-class amateur level in two districts in
      the Netherlands are participating in the study. Teams in the intervention group
      were instructed to apply The11 during each practice session throughout the 2009
      10 season. All participants of the control group continued their practice
      sessions as usual. All soccer-related injuries and related costs for each team
      were systematically reported online by a member of the medical staff. Player
      exposure to practice sessions and matches was reported weekly by the coaches.
      Also the use of The11 during the season after the intervention season will be
      monitored. DISCUSSION: Our hypothesis is that integrating the The11 exercises in
      the warm-up for each practice session is effective in terms of injury incidence,
      injury severity, healthcare use, and its associated costs and/or absenteeism.
      Prevention of soccer injuries is expected to be beneficial to adult soccer
      players, soccer clubs, the Royal Dutch Football Association (KNVB), health
      insurance companies and society.

PMID- 21177665
TI  - Effects of high-profile collisions on drink-driving penalties and alcohol-related
      crashes in Japan.
AB  - BACKGROUND: Japanese road traffic law was amended in 2002 and 2007 to increase
      the penalties for drink-driving in response to media coverage, publicity
      campaigns, and debates following high-profile alcohol-related motor-vehicle
      crashes in 1999 and 2006. OBJECTIVE: To test the hypothesis that the proportion
      of crashes involving drink-driving started to decline before the law amendments,
      because of changes in social norms and driver behaviour after the high-profile
      crashes. METHODS: In order to assess the impact of the cases in 1999 and 2006,
      time-series analyses were used to examine the trends in the proportion of crashes
      involving drink-driving, and whether there were abrupt changes in the level or
      slope at the expected time points, using monthly police data for the period
      between January 1995 and December 2008. RESULTS: In 1999, the proportion of
      alcohol-related fatal crashes in which the driver had a blood alcohol
      concentration (BAC) >=0.5 mg/ml started to decline with a slope change of -0.09
      percentage points per month (95% CI -0.15 to -0.03) but no level change, whereas
      there were no changes for drivers with a BAC <0.5. In 2006, the trends for
      drivers with a BAC >=0.5 or <0.5 showed significant level declines of -3.1 (-5.0
      to -1.2) and -1.7 (-2.5 to -0.9) percentage points, respectively, but no slope
      changes. CONCLUSIONS: Media coverage of high-profile crashes, and subsequent
      publicity campaigns and debates might have altered social norms and driver
      behaviour, reducing the proportion of alcohol-related crashes before the
      introduction of more severe penalties for drink-driving.

PMID- 21177666
TI  - Not just 'a few wisps': real-time measurement of tobacco smoke at entrances to
      office buildings.
AB  - INTRODUCTION: An unintended consequence of indoor smoking restrictions is the
      relocation of smoking to building entrances, where non-smokers may be exposed to
      secondhand smoke, and smoke from outdoor areas may drift through entrances,
      exposing people inside. Tobacco smoke has been linked to numerous health effects
      in non-smokers and there is no safe level of secondhand smoke (SHS) exposure.
      This paper presents data on levels of tobacco smoke inside and outside entrances
      to office buildings. METHODS: Real-time air quality monitors were used to
      simultaneously measure respirable particulate matter (PM(2.5); air pollutant
      particles with a diameter of 2.5 MUg or less) as a marker for tobacco smoke,
      outside and inside 28 entrances to office buildings in downtown Toronto, Ontario,
      in May and June 2008. Measurements were taken when smoking was and was not
      present within 9 m of entrances. Background levels of PM(2.5) were also measured
      for each session. A mixed model analysis was used to estimate levels of PM(2.5),
      taking into account repeated measurement errors. RESULTS: Peak levels (10 s
      averages) of PM(2.5) were as high as 496 MUg/m(3) when smoking was present. Mixed
      model analysis shows that the average outdoor PM(2.5) with smoking was
      significantly higher than the background level (p<0.0001), and significantly and
      positively associated with the number of lit cigarettes (p<0.0001). The average
      level of PM(2.5) with >= 5 lit cigarettes was 2.5 times greater than the average
      background level. CONCLUSIONS: These findings support smoke-free policies at
      entrances to buildings to protect non-smokers from exposure to tobacco smoke.

PMID- 21177667
TI  - Severity scales in community-acquired pneumonia: what matters apart from death?

PMID- 21177669
TI  - Plasmid-encoded OXA-48 carbapenemase in Escherichia coli from Israel.

PMID- 21177668
TI  - Identification and prospective validation of clinically relevant chronic
      obstructive pulmonary disease (COPD) subtypes.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is increasingly
      considered a heterogeneous condition. It was hypothesised that COPD, as currently
      defined, includes different clinically relevant subtypes. METHODS: To identify
      and validate COPD subtypes, 342 subjects hospitalised for the first time because
      of a COPD exacerbation were recruited. Three months after discharge, when
      clinically stable, symptoms and quality of life, lung function, exercise
      capacity, nutritional status, biomarkers of systemic and bronchial inflammation,
      sputum microbiology, CT of the thorax and echocardiography were assessed. COPD
      groups were identified by partitioning cluster analysis and validated
      prospectively against cause-specific hospitalisations and all-cause mortality
      during a 4 year follow-up. RESULTS: Three COPD groups were identified: group 1
      (n=126, 67 years) was characterised by severe airflow limitation
      (postbronchodilator forced expiratory volume in 1 s (FEV(1)) 38% predicted) and
      worse performance in most of the respiratory domains of the disease; group 2
      (n=125, 69 years) showed milder airflow limitation (FEV(1) 63% predicted); and
      group 3 (n=91, 67 years) combined a similarly milder airflow limitation (FEV(1)
      58% predicted) with a high proportion of obesity, cardiovascular disorders,
      diabetes and systemic inflammation. During follow-up, group 1 had more frequent
      hospitalisations due to COPD (HR 3.28, p<0.001) and higher all-cause mortality
      (HR 2.36, p=0.018) than the other two groups, whereas group 3 had more admissions
      due to cardiovascular disease (HR 2.87, p=0.014). CONCLUSIONS: In patients with
      COPD recruited at their first hospitalisation, three different COPD subtypes were
      identified and prospectively validated: 'severe respiratory COPD', 'moderate
      respiratory COPD', and 'systemic COPD'.

PMID- 21177671
TI  - Ciliates promote the transfer of the gene encoding the extended-spectrum beta
      lactamase CTX-M-27 between Escherichia coli strains.
AB  - OBJECTIVES: The mechanism by which Escherichia coli acquires multidrug resistance
      genes from other bacteria in the natural environment or livestock is still
      unclear. The ability of ciliates to promote the transfer of genes encoding
      extended-spectrum beta-lactamases (ESBLs) between the CTX-M-27 donor and
      clinically isolated recipient E. coli strains was investigated. METHODS: Equal
      amounts (~10(9) cfu) of donor cefotaxime-resistant E. coli and recipient
      ciprofloxacin-resistant E. coli strains were mixed together in the presence or
      absence of 10(5) ciliates in Page's amoeba saline for 24 h, in the presence or
      absence of certain drugs (cytochalasin D, cycloheximide and latrunculin B).
      RESULTS: Gene transfer frequency in the presence of ciliates was estimated at
      ~10(-6); in the absence of ciliates it was ~10(-10). Protein synthesis
      (cycloheximide) or phagocytosis (cytochalasin D or latrunculin B) inhibitors
      significantly reduced the frequency of gene transfer. CONCLUSIONS: Ciliates
      promote the transfer of genes encoding ESBLs between E. coli strains, implying
      that the presence of ciliates may provide a significant impact on emerging
      multidrug-resistant bacteria.

PMID- 21177672
TI  - IncA/C plasmids mediate antimicrobial resistance linked to virulence genes in the
      Spanish clone of the emerging Salmonella enterica serotype 4,[5],12:i:-.
AB  - OBJECTIVES: To broaden knowledge of the molecular bases and genetics of multidrug
      resistance in clinical isolates of Salmonella enterica serotype 4,5,12:i:-
      belonging to the Spanish clone. METHODS: The relatedness of the isolates was
      determined by phage typing and XbaI-PFGE. Resistance genes, integrons and
      transposable elements were identified by PCR amplification and sequencing.
      Plasmids were characterized by alkaline lysis, S1-PFGE, conjugation, replicon
      typing and Southern blot hybridization. RESULTS: The isolates were closely
      related and resistant to five to seven antimicrobials (ampicillin,
      chloramphenicol, gentamicin, streptomycin/spectinomycin, sulphonamides,
      trimethoprim and tetracycline, arranged in different combinations). Most of the
      responsible genes were provided by a conventional class 1 integron with the
      dfrA12-orfF-aadA2 variable region, an atypical class 1 integron containing sul3
      next to the estX-psp-aadA2-cmlA1-aadA1 variable region and a truncated Tn1721
      transposon carrying tet(A). A defective Tn21 with the mer operon and ISVsa3
      associated with sul2 were also detected. All resistance genes and mobile genetic
      elements were located on large, non-conjugative and highly variable plasmids
      carrying one (A/C) or two (A/C and N) replicons, as well as virulence genes of
      pSLT. CONCLUSIONS: IncA/C plasmids are responsible for multidrug resistance in an
      increasing number of relevant human and animal bacterial pathogens, and hence are
      regarded as an important threat to public health. Those found in the Spanish
      clone of Salmonella 4,5,12:i:- constitute a relevant example of short-term
      evolution, and could have been involved in the successful adaptation of this
      pathogen.

PMID- 21177673
TI  - Detection of hepatitis B virus genotype A3 and primary drug resistance mutations
      in African immigrants with chronic hepatitis B in Spain.
AB  - BACKGROUND: Universal vaccination and antiviral therapy have reduced chronic
      hepatitis B virus (HBV) in natives in the Western world. However, immigration
      from high HBV endemic areas continues to maintain a relatively stable prevalence
      of chronic hepatitis B in most developed countries. METHODS: All foreigners
      attending a referral infectious diseases department in Madrid, Spain, from
      January 2007 to December 2008, were evaluated for serum HBV surface antigen
      (HBsAg). Positive cases underwent further virological characterization. RESULTS:
      A total of 1718 foreigners were examined, of whom 1322 (77%) were sub-Saharan
      Africans. Serum HBsAg was positive in 121 (7%), HIV in 135 (7.9%) and hepatitis C
      virus antibodies in 212 (12.3%). HBV subgenotype A3, which so far had only been
      reported in people originating from Cameroon, was found in nearly half (14/29) of
      the tested specimens with detectable serum HBV-DNA. Interestingly, the lamivudine
      resistance mutation rtM204V was found in two Africans (6.9%), one infected with
      HBV-A3 and the other with HBV-E. Lack of prior exposure to antiviral therapy in
      these two patients was confirmed retrospectively. CONCLUSIONS: Circulation of
      uncommon HBV variants, including strains with primary drug resistance, may follow
      large immigrant flows from HBV endemic regions to Western countries. Close
      surveillance of this population is warranted, as early diagnosis and early
      antiviral therapy may reduce transmission and prevent clinical complications.

PMID- 21177674
TI  - Efficacy of carbapenems against a metallo-beta-lactamase-producing Escherichia
      coli clinical isolate in a rabbit intra-abdominal abscess model.
AB  - BACKGROUND: Although metallo-beta-lactamases (MBLs) hydrolyse most beta-lactams,
      including carbapenems, MBL-producing Enterobacteriaceae very often remain
      susceptible to carbapenems in vitro. We studied the in vivo efficacy of imipenem,
      meropenem, ertapenem and aztreonam against a carbapenem-susceptible MBL-producing
      clinical Escherichia coli strain in a rabbit intra-abdominal abscess model.
      METHODS: Rabbits were inoculated intraperitoneally with 10(8) cfu/mL of VIM-1
      positive E. coli and were assigned to receive no treatment (controls) or
      intravenous imipenem/cilastatin (imipenem) 70 mg/kg/12 h or meropenem 125
      mg/kg/12 h or ertapenem 60 mg/kg/12 h or aztreonam 70 mg/kg/12 h. Dosing regimens
      were chosen on the basis of preliminary pharmacokinetic studies so that T(>MIC)
      was achieved for >=50% of the dosing interval for all tested antibiotics. A total
      of eight doses were administered before sacrifice and the abscesses were
      harvested and quantitatively cultured. RESULTS: MICs of imipenem, meropenem,
      ertapenem and aztreonam for the infecting isolate were 1, <=0.25, 1.5 and <=0.25
      mg/L, respectively. The log(10) cfu/g (mean +/- SD) viable counts in pus were as
      follows: controls (n = 16), 8.71 +/- 1.34 (P < 0.001 versus all other groups);
      imipenem (n = 15), 4.89 +/- 2.42; meropenem (n = 15), 4.24 +/- 2.44; ertapenem (n
      = 16), 3.17 +/- 1.85 (P = 0.022 versus imipenem); and aztreonam (n = 15), 3.62 +/
      3.05. Mortality among treated rabbits was significantly reduced compared with
      controls. Four animals in the aztreonam group (26.7%) had culture-negative pus
      and no mortality was noted among aztreonam-treated animals. CONCLUSIONS: In the
      rabbit experimental model, carbapenems were shown to be effective in the
      treatment of intra-abdominal infection due to an extended-spectrum beta-lactamase
      negative carbapenem-susceptible VIM-1-producing clinical E. coli strain, but
      treatment with aztreonam resulted in a more favourable outcome overall.

PMID- 21177675
TI  - Spread of Escherichia coli O25b:H4-B2-ST131 producing CTX-M-15 and SHV-12 with
      high virulence gene content in Barcelona (Spain).
AB  - OBJECTIVES: The present study was carried out to evaluate the current prevalence
      of the clonal group O25b:H4-B2-ST131 among extended-spectrum beta-lactamase
      (ESBL)-producing Escherichia coli (ESBLEC) collected in the Hospital Vall
      d'Hebron in Barcelona (Spain) with regard to other clonal groups and to
      characterize their genetic background. METHODS: Ninety-four consecutive non
      duplicate ESBLEC isolates collected from May to December 2008 were studied. ESBL
      enzymes, phylogenetic groups, serotypes, virulence genes, sequence types (STs)
      and PFGE profiles were determined. Results The most prevalent ESBLs were CTX-M-14
      (47%), CTX-M-15 (26%) and SHV-12 (19%). Thirty (32%) of the 94 ESBLEC isolates
      belonged to the clonal group O25b:H4-B2-ST131 of which 19 (63%) carried the
      bla(CTX-M-15) gene and eight (27%) the bla(SHV-12) gene. Moreover, five
      additional clonal groups (O15/O25a:H1/HNM-D-ST393, O78:HNM-A-ST369,
      ONT:H21,42/HNM-B1-ST101, O9:H4-A-ST410 and O8:H19-B1-ST162) were detected among
      16 isolates producing CTX-M-14 and SHV-12. The 30 ST131 isolates exhibited a
      significantly higher virulence score (mean number of virulence genes 9.60 versus
      5.84) compared with the 64 non-ST131 isolates. In particular, the SHV-12
      producing ST131 isolates showed the highest virulence score (range 8-13, mean
      score 11.75). RESULTS: also revealed that the 30 ST131 isolates were distributed
      in five different groups according to their virulence, XbaI macrorestriction and
      resistance patterns. CONCLUSIONS: We report for the first time the clonal spread
      of SHV-12-producing O25b:H4-B2-ST131 isolates characterized by high virulence
      gene content. Moreover, we describe the distribution of the ST131 isolates within
      different virulence groups.

PMID- 21177676
TI  - PCR-based amplification of heterogeneous IS257-ileS2 junctions for molecular
      monitoring of high-level mupirocin resistance in staphylococci.
AB  - OBJECTIVES: Plasmids encoding the ileS2 gene are responsible for the wide spread
      of high-level mupirocin resistance in staphylococci, and consequent clinical and
      epidemiological problems. We investigated the location of insertion sequence
      IS257 flanking ileS2 in different plasmids and developed a method for molecular
      typing of the IS257-ileS2 spacer regions. METHODS: Nine ileS2-encoding plasmids
      (i.e. pPR1-pPR9) classified into distinct structural groups (i.e. S1-S4) were
      analysed. Complete DNA sequences between IS257s flanking ileS2 were determined. A
      PCR-based amplification scheme was designed for the simultaneous amplification of
      up- and down-stream IS257-ileS2 regions. The method was applied to a total of 90
      high-level mupirocin-resistant clinical isolates of methicillin-resistant
      Staphylococcus aureus (MRSA). RESULTS: pPR1-pPR9 possessed IS257s flanking ileS2.
      Plasmids of each structural group showed a unique configuration of IS257-ileS2
      spacer regions. The PCR-based method permitted accurate typing of the
      heterogeneous IS257-ileS2 up- and down-stream junctions, and the differentiation
      of plasmids of each group. The results obtained corresponded with previous
      plasmid typing based on restriction enzyme analyses and ileS2 locus hybridization
      polymorphs. The application of the PCR-based method to a diverse collection of
      MRSA isolates carrying ileS2-encoding plasmids demonstrated its versatility and
      revealed extraordinary heterogeneity in the IS257-ileS2 spacers. CONCLUSIONS: The
      devised PCR-based scheme offers a rapid, simple and effective approach for typing
      IS257-ileS2 configurations present on ileS2-encoding plasmids. Hopefully, it
      could serve as a useful molecular epidemiological tool to control high-level
      mupirocin resistance.

PMID- 21177677
TI  - Comment on: isoniazid and rifampicin resistance-associated mutations in
      Mycobacterium tuberculosis isolates from Yangon, Myanmar: implications for rapid
      molecular testing.

PMID- 21177678
TI  - The impact of seasonal and year-round transmission regimes on the evolution of
      influenza A virus.
AB  - Punctuated antigenic change is believed to be a key element in the evolution of
      influenza A; clusters of antigenically similar strains predominate worldwide for
      several years until an antigenically distant mutant emerges and instigates a
      selective sweep. It is thought that a region of East-Southeast Asia with year
      round transmission acts as a source of antigenic diversity for influenza A and
      seasonal epidemics in temperate regions make little contribution to antigenic
      evolution. We use a mathematical model to examine how different transmission
      regimes affect the evolutionary dynamics of influenza over the lifespan of an
      antigenic cluster. Our model indicates that, in non-seasonal regions, mutants
      that cause significant outbreaks appear before the peak of the wild-type
      epidemic. A relatively large proportion of these mutants spread globally. In
      seasonal regions, mutants that cause significant local outbreaks appear each year
      before the seasonal peak of the wild-type epidemic, but only a small proportion
      spread globally. The potential for global spread is strongly influenced by the
      intensity of non-seasonal circulation and coupling between non-seasonal and
      seasonal regions. Results are similar if mutations are neutral, or confer a weak
      to moderate antigenic advantage. However, there is a threshold antigenic
      advantage, depending on the non-seasonal transmission intensity, beyond which
      mutants can escape herd immunity in the non-seasonal region and there is a global
      explosion in diversity. We conclude that non-seasonal transmission regions are
      fundamental to the generation and maintenance of influenza diversity owing to
      their epidemiology. More extensive sampling of viral diversity in such regions
      could facilitate earlier identification of antigenically novel strains and extend
      the critical window for vaccine development.

PMID- 21177679
TI  - Costs of memory: lessons from 'mini' brains.
AB  - Variation in learning and memory abilities among closely related species, or even
      among populations of the same species, has opened research into the relationship
      between cognition, ecological context and the fitness costs, and benefits of
      learning and memory. Such research programmes have long been dominated by
      vertebrate studies and by the assumption of a relationship between cognitive
      abilities, brain size and metabolic costs. Research on these 'large brained'
      organisms has provided important insights into the understanding of cognitive
      functions and their adaptive value. In the present review, we discuss some
      aspects of the fitness costs of learning and memory by focusing on 'mini-brain'
      studies. Research on learning and memory in insects has challenged some
      traditional positions and is pushing the boundaries of our understanding of the
      evolution of learning and memory.

PMID- 21177680
TI  - Emergent neutrality drives phytoplankton species coexistence.
AB  - The mechanisms that drive species coexistence and community dynamics have long
      puzzled ecologists. Here, we explain species coexistence, size structure and
      diversity patterns in a phytoplankton community using a combination of four
      fundamental factors: organism traits, size-based constraints, hydrology and
      species competition. Using a 'microscopic' Lotka-Volterra competition (MLVC)
      model (i.e. with explicit recipes to compute its parameters), we provide a
      mechanistic explanation of species coexistence along a niche axis (i.e.
      organismic volume). We based our model on empirically measured quantities,
      minimal ecological assumptions and stochastic processes. In nature, we found
      aggregated patterns of species biovolume (i.e. clumps) along the volume axis and
      a peak in species richness. Both patterns were reproduced by the MLVC model.
      Observed clumps corresponded to niche zones (volumes) where species fitness was
      highest, or where fitness was equal among competing species. The latter implies
      the action of equalizing processes, which would suggest emergent neutrality as a
      plausible mechanism to explain community patterns.

PMID- 21177681
TI  - The origin and dynamic evolution of chemical information transfer.
AB  - Although chemical communication is the most widespread form of communication, its
      evolution and diversity are not well understood. By integrating studies of a wide
      range of terrestrial plants and animals, we show that many chemicals are emitted,
      which can unintentionally provide information (cues) and, therefore, act as
      direct precursors for the evolution of intentional communication (signals).
      Depending on the content, design and the original function of the cue, there are
      predictable ways that selection can enhance the communicative function of
      chemicals. We review recent progress on how efficacy-based selection by receivers
      leads to distinct evolutionary trajectories of chemical communication. Because
      the original function of a cue may channel but also constrain the evolution of
      functional communication, we show that a broad perspective on multiple selective
      pressures acting upon chemicals provides important insights into the origin and
      dynamic evolution of chemical information transfer. Finally, we argue that
      integrating chemical ecology into communication theory may significantly enhance
      our understanding of the evolution, the design and the content of signals in
      general.

PMID- 21177682
TI  - A worm's best friend: recruitment of neutrophils by Wolbachia confounds
      eosinophil degranulation against the filarial nematode Onchocerca ochengi.
AB  - Onchocerca ochengi, a filarial parasite of cattle, represents the closest
      relative of the human pathogen, Onchocerca volvulus. Both species harbour
      Wolbachia endosymbionts and are remarkable in that adult female worms remain
      viable but sessile for many years while surrounded by host cells and antibodies.
      The basis of the symbiosis between filariae and Wolbachia is thought to be
      metabolic, although a role for Wolbachia in immune evasion has received little
      attention. Neutrophils are attracted to Wolbachia, but following antibiotic
      chemotherapy they are replaced by eosinophils that degranulate on the worm
      cuticle. However, it is unclear whether the eosinophils are involved in parasite
      killing or if they are attracted secondarily to dying worms. In this study,
      cattle infected with Onchocerca ochengi received adulticidal regimens of
      oxytetracycline or melarsomine. In contrast to oxytetracycline, melarsomine did
      not directly affect Wolbachia viability. Eosinophil degranulation increased
      significantly only in the oxytetracycline group; whereas nodular gene expression
      of bovine neutrophilic chemokines was lowest in this group. Moreover, intense
      eosinophil degranulation was initially associated with worm vitality, not
      degeneration. Taken together, these data offer strong support for the hypothesis
      that Wolbachia confers longevity on O. ochengi through a defensive mutualism,
      which diverts a potentially lethal effector cell response.

PMID- 21177683
TI  - Asymmetric reproductive character displacement in male aggregation behaviour.
AB  - Reproductive character displacement--the evolution of traits that minimize
      reproductive interactions between species--can promote striking divergence in
      male signals or female mate preferences between populations that do and do not
      occur with heterospecifics. However, reproductive character displacement can
      affect other aspects of mating behaviour. Indeed, avoidance of heterospecific
      interactions might contribute to spatial (or temporal) aggregation of
      conspecifics. We examined this possibility in two species of hybridizing
      spadefoot toad (genus Spea). We found that in Spea bombifrons sympatric males
      were more likely than allopatric males to associate with calling males. Moreover,
      contrary to allopatric males, sympatric S. bombifrons males preferentially
      associated with conspecific male calls. By contrast, Spea multiplicata showed no
      differences between sympatry and allopatry in likelihood to associate with
      calling males. Further, sympatric and allopatric males did not differ in
      preference for conspecifics. However, allopatric S. multiplicata were more
      variable than sympatric males in their responses. Thus, in S. multiplicata,
      character displacement may have refined pre-existing aggregation behaviour. Our
      results suggest that heterospecific interactions can foster aggregative behaviour
      that might ultimately contribute to clustering of conspecifics. Such clustering
      can generate spatial or temporal segregation of reproductive activities among
      species and ultimately promote reproductive isolation.

PMID- 21177684
TI  - The impact of environmental change on host-parasite coevolutionary dynamics.
AB  - Environmental factors are known to affect the strength and the specificity of
      interactions between hosts and parasites. However, how this shapes patterns of
      coevolutionary dynamics is not clear. Here, we construct a simple mathematical
      model to study the effect of environmental change on host-parasite coevolutionary
      outcome when interactions are of the matching-alleles or the gene-for-gene type.
      Environmental changes may effectively alter the selective pressure and the level
      of specialism in the population. Our results suggest that environmental change
      altering the specificity of selection in antagonistic interactions can produce
      alternating time windows of cyclical allele-frequency dynamics and cessation
      thereof. This type of environmental impact can also explain the maintenance of
      polymorphism in gene-for-gene interactions without costs. Overall, our study
      points to the potential consequences of environmental variation in coevolution,
      and thus the importance of characterizing genotype-by-genotype-by-environment
      interactions in natural host-parasite systems, especially those that change the
      direction of selection acting between the two species.

PMID- 21177685
TI  - Alternative life histories in the Atlantic salmon: genetic covariances within the
      sneaker sexual tactic in males.
AB  - Alternative reproductive tactics are ubiquitous in many species. Tactic
      expression often depends on whether an individual's condition surpasses
      thresholds that are responsible for activating particular developmental pathways.
      Two central goals in understanding the evolution of reproductive tactics are
      quantifying the extent to which thresholds are explained by additive genetic
      effects, and describing their covariation with condition-related traits. We
      monitored the development of early sexual maturation that leads to the sneaker
      reproductive tactic in Atlantic salmon (Salmo salar L.). We found evidence for
      additive genetic variance in the timing of sexual maturity (which is a measure of
      the surpassing of threshold values) and body-size traits. This suggests that
      selection can affect the patterns of sexual development by changing the timing of
      this event and/or body size. Significant levels of covariation between these
      traits also occurred, implying a potential for correlated responses to selection.
      Closer examination of genetic covariances suggests that the detected genetic
      variation is distributed along at least five directions of phenotypic variation.
      Our results show that the potential for evolution of the life-history traits
      constituting this reproductive phenotype is greatly influenced by their patterns
      of genetic covariance.

PMID- 21177686
TI  - Seed-dispersal distributions by trumpeter hornbills in fragmented landscapes.
AB  - Frugivorous birds provide important ecosystem services by transporting seeds of
      fleshy fruited plants. It has been assumed that seed-dispersal kernels generated
      by these animals are generally leptokurtic, resulting in little dispersal among
      habitat fragments. However, little is known about the seed-dispersal distribution
      generated by large frugivorous birds in fragmented landscapes. We investigated
      movement and seed-dispersal patterns of trumpeter hornbills (Bycanistes
      bucinator) in a fragmented landscape in South Africa. Novel GPS loggers provide
      high-quality location data without bias against recording long-distance
      movements. We found a very weakly bimodal seed-dispersal distribution with
      potential dispersal distances up to 14.5 km. Within forest, the seed-dispersal
      distribution was unimodal with an expected dispersal distance of 86 m. In the
      fragmented agricultural landscape, the distribution was strongly bimodal with
      peaks at 18 and 512 m. Our results demonstrate that seed-dispersal distributions
      differed when birds moved in different habitat types. Seed-dispersal distances in
      fragmented landscapes show that transport among habitat patches is more frequent
      than previously assumed, allowing plants to disperse among habitat patches and to
      track the changing climatic conditions.

PMID- 21177687
TI  - Phenological variation in annual timing of hibernation and breeding in nearby
      populations of Arctic ground squirrels.
AB  - Ecologists need an empirical understanding of physiological and behavioural
      adjustments that animals can make in response to seasonal and long-term
      variations in environmental conditions. Because many species experience trade
      offs between timing and duration of one seasonal event versus another and because
      interacting species may also shift phenologies at different rates, it is possible
      that, in aggregate, phenological shifts could result in mismatches that disrupt
      ecological communities. We investigated the timing of seasonal events over 14
      years in two Arctic ground squirrel populations living 20 km apart in Northern
      Alaska. At Atigun River, snow melt occurred 27 days earlier and snow cover began
      17 days later than at Toolik Lake. This spatial differential was reflected in
      significant variation in the timing of most seasonal events in ground squirrels
      living at the two sites. Although reproductive males ended seasonal torpor on the
      same date at both sites, Atigun males emerged from hibernation 9 days earlier and
      entered hibernation 5 days later than Toolik males. Atigun females emerged and
      bred 13 days earlier and entered hibernation 9 days earlier than those at Toolik.
      We propose that this variation in phenology over a small spatial scale is likely
      generated by plasticity of physiological mechanisms that may also provide
      individuals the ability to respond to variation in environmental conditions over
      time.

PMID- 21177688
TI  - Shifting sources of productivity in the coastal marine tropics during the
      Cenozoic era.
AB  - Changes in the rates and sources of marine primary production over time are
      difficult to document owing to the absence of direct estimates of past
      productivity. Here, I use the maximum body sizes of the largest species in each
      of 23 tropical shallow-water marine molluscan guilds (groups of species with
      similar habits and trophic roles) to trace the relative importance of planktonic
      and benthic primary productivity from the Eocene (55 Ma) onwards. The largest
      members of guilds are least constrained in exploiting resources and therefore
      reflect the availability and accessibility of those resources most accurately.
      Maximum sizes of suspension-feeders and predators increased by a factor of 2.3
      and 4.0, respectively, whereas those in four out of five herbivorous guilds
      declined. I interpret these patterns, which are discernible throughout the
      coastal tropics, to mean that primary production in the Eocene marine tropics was
      concentrated on the seafloor, as is the case today on offshore reefs and islands,
      and that the Miocene to the recent interval witnessed a dramatic increase in
      planktonic productivity along continental margins. The rise in planktonic
      fertility is best explained by an increase in nutrient supply from the land
      associated with intense global tectonic activity and more vigorous ocean mixing
      owing to cooling.

PMID- 21177689
TI  - Unshelled abalone and corrupted urchins: development of marine calcifiers in a
      changing ocean.
AB  - The most fragile skeletons produced by benthic marine calcifiers are those that
      larvae and juveniles make to support their bodies. Ocean warming, acidification,
      decreased carbonate saturation and their interactive effects are likely to impair
      skeletogenesis. Failure to produce skeleton in a changing ocean has negative
      implications for a diversity of marine species. We examined the interactive
      effects of warming and acidification on an abalone (Haliotis coccoradiata) and a
      sea urchin (Heliocidaris erythrogramma) reared from fertilization in temperature
      and pH/pCO(2) treatments in a climatically and regionally relevant setting.
      Exposure of ectodermal (abalone) and mesodermal (echinoid) calcifying systems to
      warming (+2 degrees C to 4 degrees C) and acidification (pH 7.6-7.8) resulted in
      unshelled larvae and abnormal juveniles. Haliotis development was most sensitive
      with no interaction between stressors. For Heliocidaris, the percentage of normal
      juveniles decreased in response to both stressors, although a +2 degrees C
      warming diminished the negative effect of low pH. The number of spines produced
      decreased with increasing acidification/pCO(2), and the interactive effect
      between stressors indicated that a +2 degrees C warming reduced the negative
      effects of low pH. At +4 degrees C, the developmental thermal tolerance was
      breached. Our results show that projected near-future climate change will have
      deleterious effects on development with differences in vulnerability in the two
      species.

PMID- 21177691
TI  - Blackawton bees: commentary on Blackawton, P. S. et al.

PMID- 21177690
TI  - Genomic signatures of diet-related shifts during human origins.
AB  - There are numerous anthropological analyses concerning the importance of diet
      during human evolution. Diet is thought to have had a profound influence on the
      human phenotype, and dietary differences have been hypothesized to contribute to
      the dramatic morphological changes seen in modern humans as compared with non
      human primates. Here, we attempt to integrate the results of new genomic studies
      within this well-developed anthropological context. We then review the current
      evidence for adaptation related to diet, both at the level of sequence changes
      and gene expression. Finally, we propose some ways in which new technologies can
      help identify specific genomic adaptations that have resulted in metabolic and
      morphological differences between humans and non-human primates.

PMID- 21177692
TI  - After 60 years, an answer to the question: what is the Karner blue butterfly?
AB  - The Karner blue butterfly (KBB), Lycaeides melissa samuelis, is a federally
      protected taxon whose relationship to the Melissa blue, Lycaeides melissa, has
      been a point of contention during the 66 years since the KBB was first described.
      Using a large population-genomic dataset and a model of population divergence
      with migration, we investigated the relationship between the KBB and L. melissa,
      as well as the relationship between L. melissa and a third taxon, Lycaeides idas.
      We report that gene flow between the KBB and L. melissa is low, and comparable to
      gene flow between L. melissa and L. idas. Considering this population-genetic
      evidence, we conclude that the KBB is a unique evolutionary lineage that should
      be recognized as Lycaeides samuelis.

PMID- 21177693
TI  - Penguin heat-retention structures evolved in a greenhouse Earth.
AB  - Penguins (Sphenisciformes) inhabit some of the most extreme environments on
      Earth. The 60+ Myr fossil record of penguins spans an interval that witnessed
      dramatic shifts in Cenozoic ocean temperatures and currents, indicating a long
      interplay between penguin evolution and environmental change. Perhaps the most
      celebrated example is the successful Late Cenozoic invasion of glacial
      environments by crown clade penguins. A major adaptation that allows penguins to
      forage in cold water is the humeral arterial plexus, a vascular counter-current
      heat exchanger (CCHE) that limits heat loss through the flipper. Fossil evidence
      reveals that the humeral plexus arose at least 49 Ma during a 'Greenhouse Earth'
      interval. The evolution of the CCHE is therefore unrelated to global cooling or
      development of polar ice sheets, but probably represents an adaptation to
      foraging in subsurface waters at temperate latitudes. As global climate cooled,
      the CCHE was key to invasion of thermally more demanding environments associated
      with Antarctic ice sheets.

PMID- 21177694
TI  - Blackawton bees.
AB  - BACKGROUND: Real science has the potential to not only amaze, but also transform
      the way one thinks of the world and oneself. This is because the process of
      science is little different from the deeply resonant, natural processes of play.
      Play enables humans (and other mammals) to discover (and create) relationships
      and patterns. When one adds rules to play, a game is created. THIS IS SCIENCE:
      the process of playing with rules that enables one to reveal previously unseen
      patterns of relationships that extend our collective understanding of nature and
      human nature. When thought of in this way, science education becomes a more
      enlightened and intuitive process of asking questions and devising games to
      address those questions. But, because the outcome of all game-playing is
      unpredictable, supporting this 'messyness', which is the engine of science, is
      critical to good science education (and indeed creative education generally).
      Indeed, we have learned that doing 'real' science in public spaces can stimulate
      tremendous interest in children and adults in understanding the processes by
      which we make sense of the world. The present study (on the vision of bumble
      bees) goes even further, since it was not only performed outside my laboratory
      (in a Norman church in the southwest of England), but the 'games' were themselves
      devised in collaboration with 25 8- to 10-year-old children. They asked the
      questions, hypothesized the answers, designed the games (in other words, the
      experiments) to test these hypotheses and analysed the data. They also drew the
      figures (in coloured pencil) and wrote the paper. Their headteacher (Dave
      Strudwick) and I devised the educational programme (we call 'i,scientist'), and I
      trained the bees and transcribed the childrens' words into text (which was done
      with smaller groups of children at the school's local village pub). So what
      follows is a novel study (scientifically and conceptually) in 'kids speak'
      without references to past literature, which is a challenge. Although the
      historical context of any study is of course important, including references in
      this instance would be disingenuous for two reasons. First, given the way
      scientific data are naturally reported, the relevant information is simply
      inaccessible to the literate ability of 8- to 10-year-old children, and second,
      the true motivation for any scientific study (at least one of integrity) is one's
      own curiousity, which for the children was not inspired by the scientific
      literature, but their own observations of the world. This lack of historical,
      scientific context does not diminish the resulting data, scientific methodology
      or merit of the discovery for the scientific and 'non-scientific' audience. On
      the contrary, it reveals science in its truest (most naive) form, and in this way
      makes explicit the commonality between science, art and indeed all creative
      activities. PRINCIPAL FINDING: 'We discovered that bumble-bees can use a
      combination of colour and spatial relationships in deciding which colour of
      flower to forage from. We also discovered that science is cool and fun because
      you get to do stuff that no one has ever done before. (Children from
      Blackawton)'.

PMID- 21177695
TI  - Aquatic manoeuvering with counter-propagating waves: a novel locomotive strategy.
AB  - Many aquatic organisms swim by means of an undulating fin. These undulations
      often form a single wave travelling from one end of the fin to the other.
      However, when these aquatic animals are holding station or hovering, there is
      often a travelling wave from the head to the tail, and another moving from the
      tail to the head, meeting in the middle of the fin. Our study uses a biomimetic
      fish robot and computational fluid dynamics on a model of a real fish to uncover
      the mechanics of these inward counter-propagating waves. In addition, we compare
      the flow structure and upward force generated by inward counter-propagating waves
      to standing waves, unidirectional waves, and outward counter-propagating waves
      (i.e. one wave travelling from the middle of the fin to the head, and another
      wave travelling from the middle of the fin to the tail). Using digital particle
      image velocimetry to capture the flow structure around the fish robot, and
      computational fluid dynamics, we show that inward counter-propagating waves
      generate a clear mushroom-cloud-like flow structure with an inverted jet. The two
      streams of fluid set up by the two travelling waves 'collide' together (forming
      the mushroom cap) and collect into a narrow jet away from the cap (the mushroom
      stem). The reaction force from this jet acts to push the body in the opposite
      direction to the jet, perpendicular to the direction of movement provided by a
      single travelling wave. This downward jet provides a substantial increase in the
      perpendicular force when compared with the other types of fin actuation. Animals
      can thereby move upward if the fin is along the bottom midline of the body (or
      downward if on top); or left-right if the fins are along the lateral margins. In
      addition to illuminating how a large number of undulatory swimmers can use
      elongated fins to move in unexpected directions, the phenomenon of counter
      propagating waves provides novel motion capabilities for systems using robotic
      undulators, an emerging technology for propelling underwater vehicles.

PMID- 21177696
TI  - Presence of structural heart disease and left ventricular dysfunction predict
      hospitalizations for new-onset heart failure after right ventricular apical
      pacing.
AB  - AIMS: Long-standing right ventricular apical pacing (RVAP) may result in impaired
      left ventricular (LV) function and systolic heart failure (HF) in selected
      patients. However, which patients are susceptible to those harmful effects is
      unknown. METHODS AND RESULTS: In 367 consecutive patients undergoing pacemaker
      implantations (PMIs) and RVAP, the clinical, laboratory, and echocardiographic
      data before the PMIs, electrocardiographic parameters [baseline and paced QRS
      duration (QRSd)], and echocardiography were analysed. The cumulative per cent of
      those ventricularly paced (Cum%VP) was >90% in all subjects. During a mean follow
      up period of 113+/-69 months, the occurrence of HF requiring hospitalization for
      the intravenous administration of HF medications was found in 60 patients (16%;
      HF group), but not in the remaining 307 (84%; no-HF group). The prevalence of
      structural heart disease (SHD; P<0.0001), cardiothoracic ratio (P<0.0001),
      baseline left atrial size (P=0.0001), LV end-diastolic volume (P<0.005) and end
      systolic volume (P<0.0005), LV mass index (P<0.001), and baseline and paced QRSd
      (both for P<0.001) were greater in the HF group than in the no-HF group.
      Inversely, the LV ejection fraction (LVEF) in the HF group was smaller than that
      in the no-HF group (P<0.001). The multivariate Cox regression analysis revealed
      that the presence of SHD [hazard ratio (HR)=3.12; 95% confidence interval (CI),
      1.7-5.7; P<0.001] and the LVEF (<40%; HR=2.57; 95% CI, 1.09-6.07; P<0.05) were
      associated with hospitalizations due to HF after RVAP. CONCLUSION: The presence
      of SHD and an impaired LV systolic function before the PMI may predict
      hospitalizations due to HF after RVAP.

PMID- 21177697
TI  - Non-invasive imaging prior to cryoballoon ablation of atrial fibrillation: what
      can we learn?

PMID- 21177698
TI  - Ventilation through a small-bore catheter: optimizing expiratory ventilation
      assistance.
AB  - BACKGROUND: Emergency ventilation through a small-bore transtracheal catheter can
      be lifesaving in a 'cannot intubate, cannot ventilate' situation. Ejectors,
      capable of creating suction by the Bernoulli principle, have been proposed to
      facilitate expiration through small-bore catheters. In this bench study, we
      compared a novel, purpose-built ventilation ejector (DE 5) with a previously
      proposed, modified industrial ejector (SBP 07). METHODS: The generated
      insufflation pressures, suction pressures in static and dynamic situations, and
      also suction capacities and entrainment ratios of the SBP 07 and the DE 5 were
      determined. The DE 5 was also tested in a lung simulator with a simulated
      complete upper airway obstruction. Inspiratory and expiratory times through a
      transtracheal catheter were measured at various flow rates and achievable minute
      volumes were calculated. RESULTS: In a static situation, the SBP 07 showed a more
      negative pressure build-up compared with the DE 5. However, in a dynamic
      situation, the DE 5 generated a more negative pressure, resulting in a higher
      suction capacity. Employment of the DE 5 at a flow rate of 18 litre min(-1)
      allowed a minute volume through the transtracheal catheter of up to 8.27 litre
      min(-1) at a compliance of 100 ml cm H(2)O(-1). The efficiency of the DE 5
      depended on the flow rate of the driving gas and the compliance of the lung
      simulator. CONCLUSION: In laboratory tests, the DE 5 is an optimized ventilation
      ejector suitable for applying expiratory ventilation assistance. Further research
      may confirm the clinical applicability as a portable emergency ventilator for use
      with small-bore catheters.

PMID- 21177699
TI  - Estimating modifiable coronary heart disease risk in multiple regions of the
      world: the INTERHEART Modifiable Risk Score.
AB  - AIMS: Summating risk factor burden is a useful approach in the assessment of
      cardiovascular risk among apparently healthy individuals. We aimed to derive and
      validate a new score for myocardial infarction (MI) risk using modifiable risk
      factors, derived from the INTERHEART case-control study (n = 19 470). METHODS AND
      RESULTS: Multiple logistic regression was used to create the INTERHEART
      Modifiable Risk Score (IHMRS). Internal validation was performed using split
      sample methods. External validation was performed in an international prospective
      cohort study. A risk model including apolipoproteins, smoking, second-hand smoke
      exposure, hypertension, and diabetes was developed. Addition of further
      modifiable risk factors did not improve score discrimination in an external
      cohort. Split-sample validation studies showed an area under the receiver
      operating characteristic (ROC) curve c-statistic of 0.71 [95% confidence interval
      (CI): 0.70, 0.72]. The IHMRS was positively associated with incident MI in a
      large cohort of people at low risk for cardiovascular disease [12% increase in MI
      risk (95% CI: 8, 16%) with a 1-point increase in score] and showed appropriate
      discrimination in this cohort (ROC c-statistic 0.69, 95% CI: 0.64, 0.74). Results
      were consistent across ethnic groups and geographic regions. A non-laboratory
      based score is also supplied. CONCLUSIONS: Using multiple modifiable risk factors
      from the INTERHEART case-control study, we have developed and validated a simple
      score for MI risk which is applicable to an international population.

PMID- 21177700
TI  - Abnormal calcium handling in atrial fibrillation is linked to up-regulation of
      adenosine A2A receptors.
AB  - AIMS: Atrial fibrillation (AF) is associated with abnormal sarcoplasmic reticulum
      (SR) calcium release, which is promoted by adenosine A(2A) receptor (A(2A)R)
      activation. Here, we tested the hypothesis that abnormal calcium release in AF is
      linked to A(2A)R remodelling. METHODS AND RESULTS: Western blotting and
      quantitative real-time PCR were used to determine A(2A)R mRNA and protein levels
      in right atrial samples from patients with and without AF. Effects of A(2A)R
      activation on calcium handling were assessed with patch-clamp technique and
      confocal calcium imaging. A(2A)R mRNA levels and functional A(2A)Rs were
      moderately up-regulated in patients with atrial dilation and markedly up
      regulated in those with AF. Accordingly, A(2A)R stimulation significantly
      increased ryanodine receptor phosphorylation in AF patients, and spontaneous
      calcium waves increased moderately in myocytes from patients with atrial dilation
      and strongly in patients with AF (2.2 +/- 2.1 to 14.3 +/- 8.8 min(-1), n = 6, P =
      0.01). Moreover, the high baseline level of calcium waves in AF was reduced by
      A(2A)R antagonists (3.5 +/- 2.0 to 1.3 +/- 1.3 min(-1), n = 6, P = 0.007) or
      adenosine deaminase (1.7 +/- 1.5 to 0.5 +/- 0.6 min(-1), n = 10, P = 0.02)
      suggesting that A(2A)Rs are activated by endogenous adenosine. Indeed,
      intracellular perfusion with adenosine significantly increased the calcium wave
      frequency (1.1 +/- 0.8 to 8.2 +/- 3.3 min(-1), n = 8), whereas adenosine removal
      from the cytosol decreased it (2.1 +/- 0.9 to 0.3 +/- 0.3 min(-1), n = 8, P =
      0.04). CONCLUSIONS: Atrial fibrillation patients show increased A(2A)R expression
      that may account for the high baseline level of spontaneous SR calcium release
      seen in myocytes from these patients, and the ability of A(2A)R antagonists to
      reduce this abnormal calcium release points to the A(2A)R as a novel molecular
      target in AF.

PMID- 21177701
TI  - The serotonin transporter, gender, and 17beta oestradiol in the development of
      pulmonary arterial hypertension.
AB  - AIMS: Idiopathic and familial forms of pulmonary arterial hypertension (PAH)
      predominantly affect females through an unknown mechanism. Activity of the
      serotonin transporter (SERT) may modulate the development of PAH, and mice
      overexpressing SERT (SERT+ mice) develop PAH and severe hypoxia-induced PAH. In
      the central nervous system, oestrogens influence activity of the serotonin
      system. Therefore, we examined the influence of gender on the development of PAH
      in SERT+ mice and how this is modulated by female hormones. METHODS AND RESULTS:
      PAH was assessed via measurement of right ventricular systolic pressure (RVSP),
      pulmonary vascular remodelling (PVR), and right ventricular hypertrophy. Male
      SERT+ mice did not develop PAH. Female SERT+ mice demonstrated increased RVSP and
      PVR and this was abolished by ovariectomy. Following exposure to hypoxia, SERT+
      mice exhibited severe PAH and this was also attenuated by ovariectomy. Chronic
      administration of 17beta oestradiol re-established the PAH phenotype in
      ovariectomized, normoxic, and hypoxic SERT+ mice. 17beta oestradiol also up
      regulated tryptophan hydroxylase-1 (TPH1), 5-hydroytryptamine(1B) (5-HT(1B))
      receptor, and SERT expression in human pulmonary arterial smooth muscle cells
      (hPASMCs). 17beta oestradiol stimulated hPASMC proliferation and this was
      inhibited by both the TPH inhibitor para-chlorophenylalanine and the 5-HT(1B)
      receptor antagonist SB224289. CONCLUSION: 17beta oestradiol is critical to the
      development of PAH and severe hypoxia-induced PAH in female SERT+ mice. In
      hPASMCs, 17beta oestradiol-induced proliferation is dependant on de novo
      serotonin synthesis and stimulation of the 5-HT(1B) receptor. These interactions
      between the serotonin system and 17beta oestradiol may contribute to the
      increased risk of PAH associated with female gender.

PMID- 21177702
TI  - What we learned from pandemic H1N1 influenza A.

PMID- 21177704
TI  - Psychological and clinical correlates of functional somatic complaints in
      depression.
AB  - BACKGROUND: Studies have shown that functional somatic symptoms are common in
      patients of depression. However, very few studies have assessed the socio
      demographic, psychological and clinical correlates of functional somatic
      complaints in depression. METHOD: Fifty (50) patients of first-episode unipolar
      depression (except for severe depression with psychotic symptoms), aged 18 to 50
      years, with duration of depression of more than one month, with no comorbid
      psychiatric disorders and comorbid medical illnesses, and with at least one
      symptom on Bradford Somatic Inventory were assessed on the Beck's Depression
      Inventory, the Comprehensive Psychopathological Rating Scale - Anxiety Index, the
      Toronto Alexithymia Scale (Hindi version), the Somato-sensory Amplification Scale
      and the Whiteley Index. RESULTS: The most commonly reported functional somatic
      complaints were a lack of energy much of the time (98%) and feeling tired when
      not working (82%). A significant positive correlation (Pearson's product moment
      value = 0.362, p < 0.01) was found between severity of depression and number of
      functional somatic complaints. Significant negative Spearman's rank correlation (
      0.346, p < 0.05) was found between Bradford Somatic Inventory total score and
      Toronto Alexithymia Scale severity grade. A significant positive correlation
      between Bradford Somatic Inventory total score and somato-sensory amplification
      emerged only when common items were taken care of. No correlation was found
      between Bradford Somatic Inventory total score and any of the socio-demographic
      variables, age at onset of illness, total duration of illness, melancholic
      symptoms, suicidality, level of anxiety and hypochondriacal worry. Beck's
      Depression Inventory total score alone accounted for 11.3% of the variance in the
      Bradford Somatic Inventory total score. CONCLUSION: Functional somatic complaints
      are more prevalent in patients with higher severity of depression, high somato
      sensory amplification and less alexithymia. There is no correlation of functional
      somatic complaints with level of anxiety and hypochondriacal worry.

PMID- 21177705
TI  - Personality disorders: prevalence and demography at a psychiatric outpatient in
      North India.
AB  - BACKGROUND: Even though personality disorders are common among psychiatric
      populations, the data from India on their prevalence and demography are sparse.
      AIM: To profile the prevalence and demography of personality disorders in North
      India. METHODS: The retrospective study was based on patients attending the
      outpatient of a general hospital psychiatric centre in North India between June
      1996 and June 2006. The specified data were collected from the case records of
      those receiving a primary or comorbid ICD-10 diagnosis of a personality disorder.
      RESULTS: Personality disorders had a prevalence of 1.07%, with a preponderance of
      those aged 21-40 years (69.4%), men (64.9%), employed and students (37.3% and
      32.8% respectively), unmarried (56%), graduates and undergraduates (27.6% each),
      and referred by the family (68.7%). The most common personality disorders were
      anxious-avoidant and borderline. Compared with the anxious-avoidant group, the
      borderline group was younger (mean age 24.44 vs 29.66 years) and had a
      preponderance of females (60% vs 27.1%). CONCLUSION: The prevalence of
      personality disorders among the psychiatric outpatients was low compared to most
      of the research literature reporting clinically diagnosed personality disorders.
      The differences between the borderline and anxious-avoidant personality disorder
      subjects were largely explained by interrelated demographic variables.

PMID- 21177706
TI  - Assessing and quantifying inter-rater variation for dichotomous ratings using a
      Rasch model.
AB  - We present a new model-based approach to the analysis of agreement between raters
      in a situation where all raters have supplied dichotomous ratings of the same
      cases in a sample. The model is a logistic regression model with random effects-
      a Rasch model. In the rater setting, the Rasch model includes parameters that
      allow raters to have different propensities to score a given set of individuals
      positively or negatively--the rater bias. An exact score test of the hypothesis
      of no rater bias is proposed and is shown to be an exact generalised McNemar's
      test. Based on the model, we suggest quantifying the rater variation as a
      suitable measure of the variation of the rater odds ratios. An important example
      that will serve to motivate and illustrate the proposed model, is the study of
      Umbilical artery Doppler velocimetry used by obstetricians to assess the status
      of a foetus. The purpose of the assessment is to improve the foetus' chance of
      survival by choosing the optimal time of elective delivery. In the study, data
      related to 139 perinatal deaths were sent to 32 experts who were asked whether
      the use of Doppler velocimetry might have prevented each death.

PMID- 21177703
TI  - Nitrite in pulmonary arterial hypertension: therapeutic avenues in the setting of
      dysregulated arginine/nitric oxide synthase signalling.
AB  - Pulmonary arterial hypertension (PAH) is an insidious disease of the small
      pulmonary arteries that is progressive in nature and results in right heart
      strain/hypertrophy and eventually failure. The aetiologies may vary but several
      common pathophysiological changes result in this phenotype, including
      vasoconstriction, thrombosis, and vascular proliferation. Data suggest that
      nitric oxide (NO) signalling is vasoprotective in the setting of PAH. The classic
      arginine-NO synthase (NOS)-NO signalling pathway may represent an adaptive
      response that is eventually dysregulated during disease progression.
      Dysregulation occurs secondary to NOS enzyme down-regulation, enzymatic
      uncoupling, and arginine catabolism by vascular and red cell arginases and by
      direct NO inactivation via catabolic reactions with superoxide or cell-free
      plasma haemoglobin (in the case of haemolytic disease). The anion nitrite, which
      has recently been recognized as a source of NO that circumvents the arginine-NOS
      pathway, may serve as an additional adaptive signalling pathway that is now
      appreciated to have a vasoregulatory role in the pulmonary and systemic
      vasculature. Inhaled nebulized sodium nitrite is a relatively potent pulmonary
      vasodilator in the setting of hypoxia and is also anti-proliferative in multiple
      experimental models of pulmonary hypertension. Multiple nitrite reductases have
      been shown to be relevant in the conversion of nitrite to metabolically active
      NO, including deoxy-haemoglobin and myoglobin in the circulation and heart,
      respectively, and xanthine oxidoreductase in the lung parenchyma.

PMID- 21177707
TI  - How the Internet is changing the experience of bereavement by suicide: a
      qualitative study in the UK.
AB  - The aim of this qualitative study was to explore how Internet support may be
      changing the experiences of people who have been bereaved by suicide. Forty
      narrative interviews about the (whole) experience of being bereaved by suicide
      were conducted with a maximum variation sample of people living in the UK.
      Interviews were transcribed for thematic analysis. The analysis explores several
      ways in which the Internet has made a difference to the aftermath of the death.
      These include the use of e-mail and social networking sites to inform others
      about the death, making sense of the events and gaining support from an Internet
      community of others who had been similarly bereaved and setting up website
      memorials. A few people preferred not to use the Internet for this purpose or had
      no access to a computer. Few adverse consequences of Internet communities were
      mentioned. In conclusion we found evidence that the Internet is transforming the
      experience of bereavement by suicide, most dramatically through providing access
      to other people's experiences.

PMID- 21177708
TI  - Exploring patients' experience of receiving information about cancer: a
      comparison of interview and questionnaire methods of data collection.
AB  - Patient information is widely regarded both as a resource and an entitlement: a
      means of 'empowering' patients to behave as 'consumers' of health care. Patient
      'satisfaction' has come to be regarded as an important outcome of care. This
      article presents qualitative interview data regarding the experience of patient
      information provision and the results of a self-completed Information
      Satisfaction Questionnaire (ISQ) among patients and relatives affected by cancer.
      It considers the implications of the differences between these for service
      evaluation and current policy implementation promoting patients as informed and
      expert consumers of health care. The study findings contribute to growing
      evidence that the high rate of patients' expressed satisfaction with different
      aspects of service provision as indicated by structured questionnaire responses
      is largely an artefact of the method of data collection. Accounts of negative
      experiences were common, but did not translate into expressed criticism or overt
      dissatisfaction. It is important that the limitations of such surveys are
      contextualized in relation to qualitative findings such as those of the present
      study. Especially in the face of serious and life-threatening illness,
      professional constructs such as 'information delivery', 'satisfaction' and
      'shared decision making' have little resonance for many patients, who prefer to
      trust in professional expertise and to eschew the acquisition of specialist
      knowledge and active involvement in decisions about health care.

PMID- 21177709
TI  - Heterosexual couples' uses and meanings of ovarian stimulation: Relatedness,
      embodiment and emotions.
AB  - This article is about how ovarian stimulation is understood within the context of
      heterosexual couples' relationships. The empirical research involves 15 semi
      structured interviews with patients in Portugal who have undergone IVF programmes
      performed with eggs collected in stimulated cycles. We argue that the uses and
      meanings of ovarian stimulation expressed in the patients' narratives represent
      situated values and knowledges conveyed by existing emotional resources within
      multiple gendered relations and identities. We discuss how empirical
      reconfigurations work in a mode of conversion of physical and emotional pain so
      that the application of subcutaneous injections to women's bodies makes sense
      within IVF couples' daily routine and in their conjugal relationship. The
      different practices of men's involvement in the injection of hormones into
      women's bodies are perceived as emotional moments, and men's cooperation and/ or
      protection seems to be essential in this domain. The cultural assumptions
      underlying women's duties regarding maternity reinforce a moral framework in
      which the pain and the complications associated with the ovarian stimulation are
      naturalized, normalized and accepted.

PMID- 21177710
TI  - 'I take a small amount of the real product': Elevated cholesterol and everyday
      medical reasoning in liminal space.
AB  - The medical consequences of elevated cholesterol are widely known, as are the
      medical regimens to control and manage it. At the same time, elevated cholesterol
      is bereft of bodily signs. Being symptomless places the condition in a no man's
      land: people with elevated cholesterol are assessed as medically sick but their
      bodies signal wellness. In this article I refer to this ambiguous grey area,
      betwixt and between being healthy and being sick, as liminal space . The aim of
      this article is to show how people manage the symptomless condition of elevated
      cholesterol in liminal space. Particular attention is paid to everyday medical
      reasoning in that space. Based on interviews with people with elevated
      cholesterol, I show that medical regimens are 'up against' - challenged by - a
      variety of competing conditions in everyday life, illustrating ambiguity. Facing
      this dilemma between medicine and everyday life, they ongoingly need to navigate 
      edit, modify, adjust - medical regimens against everyday conditions. This
      navigating work can be seen as ritualized strategies to sort ambiguity. People
      with elevated cholesterol do not so much act 'against medical regimens' as they
      simultaneously need to take account of other matters they are up against in
      trying to stay healthy. Medical regimens are sometimes central, sometimes
      peripheral. Adapting medical regimens to the situation at hand, people
      continuously comply with medical regimens, producing and reproducing medical
      regimens in moral contexts of everyday life.

PMID- 21177711
TI  - The experience of using complementary therapies after a diagnosis of cancer: a
      qualitative synthesis.
AB  - This article describes a qualitative synthesis of published research on cancer
      patients' experiences of complementary therapies. We conducted a systematic
      search for qualitative studies on this subject published between 1998 and 2007.
      Twenty-six refereed journal articles met the inclusion criteria. These 26
      articles were repeatedly read by the research team and key concepts emerging from
      them were identified. Differences and variations were examined in association
      with treatment, therapy type and by stage of cancer (early stage, mid-treatment,
      advanced cancer, palliative care and long term 'survivors'). Six overarching
      concepts were located, which describe the key aspects of patients' experiences of
      the use of complementary and alternative medicine after a diagnosis of cancer:
      Connection; Control; Well-being; Transformation; Integration; and Polarization.
      These are described in a 'line of argument' synthesis, and differences associated
      with treatment type and stage of disease are noted. The findings are presented in
      a table showing the six concepts according to treatment type and stage; as a
      composite story; and in a diagrammatic model showing the individual, practitioner
      and organizational levels. The synthesis identified various specific ways in
      which complementary therapies supported cancer patients, as well as occasional
      negative effects. The most notable barrier was the perceived polarization of
      complementary therapies and biomedicine; patients reported better experiences in
      integrated settings.

PMID- 21177712
TI  - Influences of organizational features of healthcare settings on clinical decision
      making: qualitative results from a cross-national factorial experiment.
AB  - A proliferating literature documents cross-national variation in medical practice
      and seeks to explain observed differences in terms of the presence of certain
      kinds of healthcare systems, economic, and cultural differences between
      countries. Less is known about how providers themselves understand these
      influences and perceive them as relevant to their clinical work. Using
      qualitative data from a cross-national factorial experiment in the United States
      and United Kingdom, we analyze 244 primary care physicians' explanations of how
      organizational features of their respective healthcare settings influence the
      treatment decisions they made for a vignette patient, including affordability of
      care; within-system quality deficits; and constraints due to patient behavior.
      While many differences are attributed to financial constraints deriving from two
      very differently structured healthcare systems, in other ways they are
      reflections of cultural and historical expectations regarding medical care, or
      interactions between the two. Implications, including possible challenges to the
      implementation of universal care in the USA, are discussed.

PMID- 21177713
TI  - Communicative disability and stories: Towards an embodied conception of
      narratives.
AB  - In this article we show that persons with communicative disabilities are often
      involved in storytelling that does not necessarily conform to the conventional
      expectations of what constitutes a narrative. By analyzing the relationship
      between story and storytelling event, and the relation between what could be
      called the primary storyteller and the vicarious storyteller, we show that
      storytellers with communicative disabilities are often quite inventive in finding
      ways of presenting themselves as competent storytellers even though they may have
      certain problems vocally animating a coherent, structured story. This lead us to
      conclude a necessary redefinition of what a narrative is - that it could be
      performed as well as it could be told - and that such a redefinition stresses
      methodological issues: in order to be able to study the life stories of people
      with communicative disabilities we need to use both narrative and ethnographic
      research methods.

PMID- 21177714
TI  - Prostate cancer support groups, health literacy and consumerism: are community
      based volunteers re-defining older men's health?
AB  - In this article we describe the connections between prostate cancer support
      groups (PCSGs) and men's health literacy and consumer orientation to health care
      services. The study findings are drawn from participant observations conducted at
      16 PCSGs in British Columbia, Canada and 54 individual interviews that focused on
      men's experiences of attending group meetings. Men's communication and
      interactions at PCSGs provide important insights for how men talk about and
      conceptualize health and illness. For example, biomedical language often
      predominated at group meetings, and men used numbers and measures to engage with
      risk discourses in linking prostate cancer markers to various treatment options
      and morbidity and mortality rates. Many groups afforded opportunities for men to
      interact with health care providers as a means to better understand the language
      and logic of prostate cancer management. The health literacy skills fostered at
      PCSGs along with specific group-informed strategies could be mobilized in the
      men's subsequent clinical consultations. Consumer discourses and strategies to
      contest power relations with health care professionals underpinned many men's
      search for prostate cancer information and their commitment to assisting other
      men. Key were patients' rights, and perhaps responsibility, to compare diverse
      health products and services in making decisions across the entire trajectory of
      their prostate cancer. Overall, the study findings reveal PCSGs as having the
      capacity to contest as well as align with medical expertise and services
      facilitating men's transition from patient to informed health care consumers. The
      processes through which this occurs may direct the design of older men's health
      promotion programs.

PMID- 21177716
TI  - The dynamics of socio-connective trust within support networks accessed by
      informal caregivers.
AB  - This article introduces the concept of socio-connective trust, the synapse
      between the social structures and processes that underpin relationships in
      supportive care networks. Data from an ethnographic case study of 18 informal
      caregivers providing in-home care for people with life-limiting illness were
      analysed drawing on theoretical concepts from the work of Giddens and writings on
      social capital, as well as the construction of trust in the caregiving
      literature. While conceptions of trust were found to contribute to understanding
      supportive care relationships, they did not account for the dynamic nature of the
      availability and use of support networks. Instead, informal caregivers undertook
      ongoing reflexive negotiation of relationship boundaries in response to their own
      conception of the current situation and their perception of trust in their
      relationships with the various members of the support network. The concept of
      socio-connective trust describes the movement and flow of the flexible bonds that
      influence relationships among care networks and determine the type and range of
      support accessed by informal caregivers. Understanding the complexities of socio
      connective trust in caregiving relationships will assist health and social care
      workers to mobilize relevant resources to support informal caregivers.

PMID- 21177715
TI  - 'I put it on the back burner most days': Living with chronic risk.
AB  - Continued advances in genetics and genomics research suggest that more and more
      people will be identified 'at risk' for common diseases such as cancer, heart
      disease or diabetes. A perspective for understanding how people adapt to and
      manage inherited risk, as well as identifying differences in individual response
      to DNA information would be useful in the planning and provision of genetics
      health services. This article adopts a 'chronic risk' perspective to explore
      living at risk of Huntington disease (HD), a fatal genetic disorder. Qualitative
      data analysis suggested two broad themes that illustrated living with chronic
      risk: (1) biographical disruption, including threats to self-identity and changes
      to relationships with others; and (2) zones of relevance, the conditions under
      which risk is or is not salient. Findings are relevant to the provision of
      genetics health services, particularly in follow-up support to individuals at
      risk for HD and their families.

PMID- 21177717
TI  - Mental health and stigma in the medical profession.
AB  - Until recently, much of the recent upsurge in interest in physician health has
      been motivated by concerns about improving patient care and patient safety and
      reducing medical errors. Increasingly, more attention has turned to examining how
      the management of mental illness among physicians might be improved within the
      medical profession and one key direction for change is the reduction of stigma
      associated with mental illness. I begin this article by presenting a brief
      overview of the stigma process from the general sociological literature. Next, I
      provide evidence that illustrates how the stigma of mental illness thrives in the
      medical profession as a result of the culture of medicine and medical training,
      perceptions of physicians and their colleagues, and expectations and responses of
      health care systems and organizations. Lastly, I discuss what needs to change by
      proposing ways of educating and raising awareness regarding mental illness among
      physicians, discussing approaches to assessing and identifying mental health
      concerns for physicians and by examining how safe and confidential support and
      treatment can be offered to physicians in need. I rely on strategically selected
      studies to effectively draw attention to and support the central themes of this
      article.

PMID- 21177718
TI  - Constructing the 'gender-specific body': A critical discourse analysis of
      publications in the field of gender-specific medicine.
AB  - Gender-specific medicine, a new and increasingly influential ethos within medical
      research and practice, has received little critical attention to date. The
      objective of this article is to critically examine the attributes of gender
      specific medicine as imparted by its advocates. Through a critical discourse
      analysis of its two leading academic journals, we identify five interrelated
      discourses: of male/female difference; of hegemonic biology; of men's
      disadvantages; of biological and social reductionism; and of the fragmented body.
      Together these comprise a master discourse of the 'gender-specific body'. The
      discourse of the 'gender-specific body' is discussed in relation to the current
      neoliberal political agenda which frames healthcare as a market good and locates
      health and illness in individual bodies rather than in the wider social
      arrangements of society. We argue that the 'gender-specific body' threatens not
      only to turn back the clock to a vision of the biological body as fixed and
      determinate, but to extend this ever deeper into the social imagination. Lost in
      the process is any meaningful sense of the human body as a relatively open system
      which develops in interaction with its social world. We propose that, as it gains
      momentum, the 'gender-specific body' is likely progressively to circumscribe our
      thinking about the health of women and men in potentially problematic ways.

PMID- 21177719
TI  - When resources get sparse: a longitudinal, qualitative study of emotions, coping
      and resource-creation when parenting a young child with severe disabilities.
AB  - Parents who realize that their newborn child is severely disabled often
      experience severe physical and emotional stress. Parental well-being is essential
      for the care-taking of the child. It is yet not known why some cope well and
      others do not. The aim of this study was to explore how parents coped with
      parenting a disabled child and how they maintained their energy and personal
      resources. We explored parents' experiences, coping and resources over a two-year
      period after their child was diagnosed with a severely disabling condition using
      a qualitative, longitudinal approach. Findings were interpreted in a theoretical
      framework of Lazarus and Folkman's studies on coping and Fredrickson's broaden
      and-build theory of positive emotions, as well as theories of positive illusions
      and benefit finding during severe adversity. We found that parents continually
      created and sustained their personal resources through positive cognitive
      reappraisals of their circumstances, the consequences of those circumstances and
      their coping possibilities. Nine main coping strategies were identified
      constituting transformative pathways in resource-creation. A theory of resource
      creation is proposed as an addition to the current understanding of coping and
      the role of positive emotions. Coping and resources were found to be closely
      interrelated and portals of intervention are discussed.

PMID- 21177720
TI  - 'A beautiful show of strength': weight loss and the fat activist self.
AB  - This article explores the disciplinary and productive effects of late 20th
      century/early 21st-century discourse around the obesity epidemic. For my
      purposes, both the Fat Activist and Weight Loss Surgery patient may be seen as
      outcomes of this discursive proliferation. Based on a content analysis of two
      online accounts of weight loss by prominent fat activists, I examine the ways in
      which such public declarations can be seen as contemporary examples of Foucault's
      notion of the confession. Through debates in the 'fatosophere', such activists
      and their peers simultaneously take up and reject both biomedical and fat
      activists tenets in ways that are highly ambivalent. In the process, fat activism
      unsettles and resituates its borders and boundaries and the issue of weight loss
      becomes a discursive technique of knowledge/power for the understanding of and
      relating to the fat activist self.

PMID- 21177721
TI  - A qualitative analysis of changes in relationship dynamics and roles between
      people with cancer and their primary informal carer.
AB  - It is widely accepted that cancer is an intersubjective experience that impacts
      upon the psychological well-being of people with cancer and informal carers, as
      well as on couple relationships. This qualitative study examined the nature and
      consequences of cancer on the relationship between informal carers and the person
      with cancer, from the perspective of Australian cancer carers. Sixty-two carers
      (42 women and 20 men), across a range of cancer types, stages and relationship
      dyads took part in semi-structured interviews. Participants reported that cancer
      had precipitated a change in roles and in the dynamics of the relationship,
      including having to take on quasi-medical tasks and decisions, neglecting self
      and other relationships, changes to the emotions or personality of the person
      with cancer, changed patterns of communication, and changes to sexuality and
      intimacy. The impact of the changed relationship included sadness, anger and
      frustration, as well as feelings of love and being closer together, resulting in
      relationship enhancement. Women were more likely to report changes in the person
      with cancer and to mourn the previous relationship, while more men reported
      relationship enhancement.

PMID- 21177722
TI  - The impact of balanced hydroxylethyl starch cardiopulmonary bypass priming
      solution on the fibrin part of clot formation: ex vivo rotation
      thromboelastometry.
AB  - INTRODUCTION: Balanced colloidal priming solutions are supposed to further
      minimize the effects of cardiopulmonary bypass (CPB) on haemostasis as compared
      to gelatin-based preparations. This exploratory study investigated whether clot
      formation, in particular the fibrin part of the clot, is less altered by a modern
      balanced HES solution as compared to a gelatin-based priming solution. METHODS:
      CPB priming solutions containing 60% gelatin (Gelofusin(r)) or balanced HES
      starch (100% or 60% Tetraspan(r)) were mixed with blood samples from healthy
      volunteers and compared with respect to their impact on clotting time (CT), alpha
      angle, maximum clot firmness (MCF), and fibrinogen, using thromboelastometry.
      RESULTS: The 100% and 60% HES priming solutions significantly increased the EXTEM
      CT from 66 +/- 9 s to 82 +/- 19 and 83 +/- 13, respectively (both P<0.05 vs.
      baseline). The speed of solid clot formation decreased significantly for all
      priming solutions compared with baseline values. The INTEM MCF decreased from 59
      +/- 4 mm to 47 +/- 4, 44 +/- 4 and 43 +/- 3 mm, whereas the EXTEM MCF decreased
      from 57 +/- 4 mm to 51 +/- 4, 51 +/- 4 and 50 +/- 4 mm after dilution with 60%
      gelatin, 100% HES or 60% HES priming solution, respectively (all P<0.01 vs.
      baseline). The priming solutions containing HES induced the largest decrease in
      MCF attributed to fibrinogen from 12 +/- 3 mm to 4 +/- 4 mm and 3 +/- 2 mm (both
      P<0.05) for the 100% and mixed priming solution, respectively. CONCLUSIONS: Ex
      vivo rotation thromboelastometry did not reveal the expected preservation of
      coagulation parameters, in particular the fibrin part of clot formation, by a
      balanced HES priming solution.

PMID- 21177723
TI  - Transfusion of shed mediastinal blood reduces the use of allogenic blood
      transfusion without increasing complications.
AB  - BACKGROUND: Reduced use of allogenic blood components is a key issue in cardiac
      surgery. Several methods to conserve blood have been used; reinfusion of shed
      mediastinal blood (RSMB) has found widespread acceptance, but the efficacy and
      safety are still debated. The purpose of this study was to evaluate the effects
      of RSMB on the use of allogenic blood components and selected complications.
      MATERIAL AND METHODS: Six hundred and twenty-three consecutive cardiac surgery
      patients in three successive periods, of whom patients in the middle period did
      not receive RSMB due to manufacturer delivery problems, were evaluated. Patients
      and procedures were characterized by EuroSCORE. Prospective collected data were:
      units of transfused allogenic blood, fresh frozen plasma (FFP) and platelets,
      postoperative blood loss and postoperative complications such as dialysis, re
      operation due to bleeding, sternal infection and stroke. Length of stay in ICU
      was used as a general indicator of perioperative complications. RESULTS: The
      number of patients receiving allogenic blood in periods with RSMB was
      significantly lower (36.5% versus 54.9%, p<0.005), while no difference was seen
      in FFP and platelets. The average number of transfused blood units was lower in
      patients receiving RSMB (2.07 versus 3.41, p=0.029), while FFP (1.34 versus 2.01,
      p=0.11) and platelets (0.58 versus 0.95, p=0.05) were not statistically
      significantly different. Postoperative bleeding was lower (759 versus 967 ml,
      p=0.032) in the periods with RSMB. CONCLUSION: Patients receiving RSMB were less
      transfused with allogenic blood and had less postoperative drainage, while the
      frequency of observed postoperative complications was not different from patients
      who did not receive RSMB.

PMID- 21177724
TI  - Biocompatibility and pathways of initial complement pathway activation with
      Phisio- and PMEA-coated cardiopulmonary bypass circuits during open-heart
      surgery.
AB  - A randomized open-heart surgery study comprising 30 patients was undertaken to
      compare the biocompatibility of Phisio-(phosphorylcholine) and PMEA-(poly-2
      methoxyethyl acrylate) coated cardiopulmonary bypass (CPB) circuits and to assess
      the initial complement pathway activation during open-heart surgery. Blood
      samples were obtained at five time points, from the start of surgery to 24 hours
      postoperatively. The following analyses were performed: haemoglobin, lactate
      dehydrogenase, leukocyte and platelet counts, myeloperoxidase and neutrophil
      activating peptide-2, thrombin-anti-thrombin complexes, syndecan-1 and the
      complement activation products C1rs-C1-inhibitor complexes, C4bc, C3bc, C3bBbP
      and the terminal complement complex (TCC). No significant inter-group difference
      was found in any parameters, except for the concentration of TCC which was
      moderately lower in the PMEA group at termination of CPB. Complement activation
      during open-heart surgery was mainly mediated through the alternative pathway. In
      conclusion, PMEA- and Phisio-coated circuits displayed similar biocompatibility
      with respect to inflammatory and haemostatic responses during and after open
      heart surgery.

PMID- 21177725
TI  - Increased preoperative thrombin generation and low protein S level associated
      with unfavorable postoperative hemodynamics after coronary artery bypass
      grafting.
AB  - In a previous study, preoperative levels of activated protein C (APC) were
      associated with unfavorable postoperative hemodynamics after coronary artery
      bypass grafting (CABG). Protein C is activated by thrombin. Protein S, the
      cofactor of activated protein C, has activated protein C-independent
      anticoagulant activity and cytoprotective effects. Therefore, the objective of
      this study was to test whether preoperative, baseline levels of either thrombin
      or protein S were associated with hemodynamic performance or markers of
      myocardial damage after CABG. One hundred patients undergoing elective on-pump
      CABG were prospectively studied. Prothrombin fragment F1+2 (a marker of thrombin
      generation) and free protein S were measured preoperatively and cardiac index,
      systemic vascular resistance index (SVRI), and pulmonary vascular resistance
      index (PVRI) were measured serially thereafter at fixed time points. Cardiac
      biomarkers CK-MBm and TnT were measured postoperatively. There was an inverse
      correlation between preoperative F1+2 and free protein S levels (r= -0.30,
      p=0.003). High preoperative F1+2 and low preoperative protein S levels were
      associated with a less favorable hemodynamic profile postoperatively. Patients
      with F1+2 in the highest decile (>=0.85 nmol/l) and patients with preoperative
      protein S in the lowest decile (<=63%) had lower CI values, and higher pulmonary
      and systemic vascular resistance index values postoperatively than comparison
      patients. Preoperative F1+2 or protein S did not correlate with postoperative
      cardiac biomarker levels. Baseline activation of coagulation and the balance
      between pro-coagulant and anti-coagulant factors preoperatively might have
      implications for postoperative hemodynamic recovery after CABG.

PMID- 21177726
TI  - Hemolysis and ECMO pumps in the 21st Century.

PMID- 21177727
TI  - Interleukin-6 G-174C gene polymorphism and serum resistin levels in North Indian
      women: potential risk of metabolic syndrome.
AB  - The present investigations were aimed to identify the possible association
      between genetic polymorphism in interleukin-6 (IL-6) G-174C gene, which confers
      susceptibility to metabolic syndrome, and serum level of resistin in North Indian
      women. The study population comprised 370 unrelated Indian women (192 having
      abdominal obesity and 178 controls). Polymorphism in genotype (CC+GC) of IL-6 G
      174C gene was determined using a combination of polymerase chain reaction (PCR)
      and sequence-specific primer with restriction fragment length polymorphism (RFLP)
      technology. Insulin resistance (IR) and serum resistin level were also analyzed
      along with metabolic risk factors. Of 192 abdominal obese women, 147 (76.56%)
      were found to have mutant CC+GC (p = 0.001) genotype and allele frequency (p =
      0.001), which was significantly higher 45 (23.44%) than non-obese and their
      respective wild type. The mutant genotype (CC+GC) of IL-6 gene was found to be
      associated significantly with high triglyceride (p = 0.025) and resistin level (p
      < 0.001), when compared with respective wild genotype (GG) in obese women. Non
      obese women with no signs of metabolic risk factors were found to have
      significantly low level of serum resistin and IR in comparison to obese women
      having genetic polymorphism for IL-6 G-174C gene. Study suggests that IL-6 G-174C
      gene is one among the susceptibility loci for metabolic syndrome in North Indian
      women. Genotype for this polymorphism may prove informative for prediction of
      genetic risk for metabolic syndrome. Further, high level of serum resistin
      molecules may be targeted to correlate with metabolic syndrome risk factors and
      could be used as early prediction marker.

PMID- 21177728
TI  - Toxicities of raw Alocasia odora.
AB  - Alocasia, the Araceae family, is a genus of more than 100 species of perennial,
      herbaceous, diminutive to extremely large, usually robust herbs with a clear-to
      milky latex. They are distributed throughout subtropical and tropical Asia and in
      the tropical western pacific as well as eastern Australia. Despite easy access to
      A odora, there have been no published reports in English regarding the toxic
      symptoms following the ingestion of raw A odora. Here, the clinical
      manifestations of 2 patients that ingested raw A odora are described. Two
      patients experienced oral numbness and intractable tongue pain, and 1 patient
      required endotracheal intubation because of upper respiratory tract obstruction.
      Although conservative treatment is the primary approach to A odora poisoning,
      physicians should be aware of the potential for upper respiratory obstruction in
      patients exposed to A odora, as well as the need for controlling tongue pain.

PMID- 21177729
TI  - Protective effect of sodium aescinate on lung injury induced by methyl parathion.
AB  - Methyl parathion (MP) is a high venenosus insecticide. It has been used in pest
      control of agriculture for several years. The present study is performed to
      investigate the protective effect of sodium aescinate (SA) on lung injury induced
      by MP. Forty male Sprague-Dawley rats are randomly divided into five groups, with
      8 animals in each group: control group, MP administration group, MP plus SA at
      doses of 0.45 mg/kg, 0.9 mg/kg and 1.8 mg/kg groups. Acetylcholinesterase (AChE)
      activity and nitric oxide (NO) level in plasma, myeloperoxidase (MPO) activity,
      NO level, and antioxidative parameters in lung tissue are assayed.
      Histopathological examination of lung is also performed. The results show that SA
      has no effect on AChE. Treatment with SA decreases the activity of MPO in lung
      and the level of NO in plasma and lung. The level of malondialdehyde in lung is
      decreased after SA treatments. SA increases the activities of superoxide
      dismutase, glutathione peroxidase and the content of glutathione in lung. SA
      administration also ameliorates lung injury induced by MP. The findings indicate
      that SA could protect lung injury induced by MP and the mechanism of action is
      related to the anti-inflammatory and anti-oxidative effect of SA.

PMID- 21177730
TI  - The effect of uremic toxin cyanate (OCN-) on anaerobic sulfur metabolism and
      prooxidative processes in the rat kidney: a protective role of lipoate.
AB  - Cyanate and its active form isocyanate are formed mainly in the process of
      nonenzymatic urea biodegradation. Cyanate is capable of protein S- and N
      carbamoylation, which can affect their activity. The present studies aimed to
      demonstrate the effect of cyanate on activity of the enzymes implicated in
      anaerobic cysteine metabolism and cyanide detoxification and on glutathione (GSH)
      level and peroxidative processes in the kidney. In addition, we examined whether
      a concomitant treatment with lipoate, a dithiol that may act as a target of S
      carbamoylation, can prevent these changes. The studies were conducted in Wistar
      rats. The animals were assigned to four groups, which received injections of
      physiological saline, cyanate (200 mg/kg), cyanate (200 mg/kg) + lipoate (100
      mg/kg) and lipoate alone (100 mg/kg). The animals were killed 2 h after the first
      injection, the kidneys were isolated and kept at -80 degrees C until biochemical
      assays were performed. Cyanate inhibited rhodanese (TST) and mercaptopyruvate
      sulfotransferase (MPST) activity, decreased GSH level and enhanced peroxidative
      processes in the kidney. All these changes were abolished by cyanate treatment in
      combination with lipoate.

PMID- 21177731
TI  - Combined effects of niacin and chromium treatment on heart of hyperlipidemic
      rats.
AB  - The present study was undertaken to investigate the effects of the combination of
      niacin and chromium(III)-chloride on heart glutathione (GSH), lipid peroxidation
      (LPO) levels, serum paraoxonase (PON), gamma-glutamyl transferase (GGT)
      activities and protein carbonyl contents (PCC) of hyperlipidemic rats. In this
      study, female Swiss albino rats were used. They were divided into four groups.
      The animals of the first group (group I) were fed with pellet chow. The rats
      (group II) were fed with a lipogenic diet consisting of 2% cholesterol, 0.5%
      cholic acid and 20% sunflower oil added to the pellet chow, and given 3%
      alcoholic water for 60 days. The rats (group III) were fed with the same
      lipogenic diet and treated by gavage technique with CrCl(3) 6H(2)O to a dose of
      250 ug/kg and 100 mg/kg niacin for 45 days, 15 days after experimental animals
      were done hyperlipidemic. Group IV was fed with pellet chow and treated with 250
      ug/kg CrCl(3) 6H(2)O and 100 mg/kg niacin for 45 days. On the 60th day, the heart
      tissue and blood samples were taken from animals. As a result, heart LPO, serum
      GGT activity and serum PCC were increased; serum PON activity and heart GSH
      levels were decreased in hyperlipidemic rats. Treatment with combined niacin and
      chromium reversed these effects. In conclusion, the combined treatment with
      niacin and chromium might induce a protective effect on heart tissue.

PMID- 21177732
TI  - The many facets of optogenetics. Introduction.

PMID- 21177733
TI  - Chronic fatigue syndrome is not caused by XMRV virus, study shows.

PMID- 21177734
TI  - Transmission of HIV to infants whose mothers seroconvert postnatally.

PMID- 21177736
TI  - Suprapubic pain, frequency, and haematuria--with a twist.

PMID- 21177735
TI  - Mother to child transmission of HIV among Zimbabwean women who seroconverted
      postnatally: prospective cohort study.
AB  - OBJECTIVES: To estimate the rates and timing of mother to infant transmission of
      HIV associated with breast feeding in mothers who seroconvert postnatally, and
      their breast milk and plasma HIV loads during and following seroconversion,
      compared with women who tested HIV positive at delivery. DESIGN: Prospective
      cohort study. SETTING: Urban Zimbabwe. PARTICIPANTS: 14 110 women and infants
      enrolled in the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) trial (1997
      2001). MAIN OUTCOME MEASURES: Mother to child transmission of HIV, and breast
      milk and maternal plasma HIV load during the postpartum period. RESULTS: Among
      mothers who tested HIV positive at baseline and whose infant tested HIV negative
      with polymerase chain reaction (PCR) at six weeks (n=2870), breastfeeding
      associated transmission was responsible for an average of 8.96 infant infections
      per 100 child years of breast feeding (95% CI 7.92 to 10.14) and varied little
      over the breastfeeding period. Breastfeeding associated transmission for mothers
      who seroconverted postnatally (n=334) averaged 34.56 infant infections per 100
      child years (95% CI 26.60 to 44.91) during the first nine months after maternal
      infection, declined to 9.50 (95% CI 3.07 to 29.47) during the next three months,
      and was zero thereafter. Among women who seroconverted postnatally and in whom
      the precise timing of infection was known (<=90 days between last negative and
      first positive test; n=51), 62% (8/13) of transmissions occurred in the first
      three months after maternal infection and breastfeeding associated transmission
      was 4.6 times higher than in mothers who tested HIV positive at baseline and
      whose infant tested HIV negative with PCR at six weeks. Median plasma HIV
      concentration in all mothers who seroconverted postnatally declined from 5.0
      log(10) copies/mL at the last negative enzyme linked immunosorbent assay (ELISA)
      to 4.1 log(10) copies/mL at 9-12 months after infection. Breast milk HIV load in
      this group was 4.3 log(10) copies/mL 0-30 days after infection, but rapidly
      declined to 2.0 log(10) copies/mL and <1.5 log(10) copies/mL by 31-90 days and
      more than 90 days, respectively. Among women whose plasma sample collected soon
      after delivery tested negative for HIV with ELISA but positive with PCR (n=17),
      75% of their infants were infected or had died by 12 months. An estimated 18.6%
      to 20.4% of all breastfeeding associated transmission observed in the ZVITAMBO
      trial occurred among mothers who seroconverted postnatally. CONCLUSIONS:
      Breastfeeding associated transmission is high during primary maternal HIV
      infection and is mirrored by a high but transient peak in breast milk HIV load.
      Around two thirds of breastfeeding associated transmission by women who
      seroconvert postnatally may occur while the mother is still in the "window
      period" of an antibody based test, when she would test HIV negative using one of
      these tests. Trial registration Clinical trials.gov NCT00198718.

PMID- 21177739
TI  - Does long term aspirin prevent cancer?

PMID- 21177740
TI  - Bad medicine: general practice.

PMID- 21177742
TI  - US government report recommends a "principle of regulatory parsimony" for
      synthetic biology.

PMID- 21177743
TI  - Quantitative meta-analysis on state and trait aspects of auditory verbal
      hallucinations in schizophrenia.
AB  - Auditory verbal hallucinations (AVHs) have a high prevalence in schizophrenic
      patients. An array of studies have explored the neural correlates of AVHs by
      means of functional neuroimaging and have associated AVHs with diverse brain
      regions, some of which have been shown to be involved in speech generation,
      speech perception, and auditory stimulus processing. We divided these studies
      into "state" studies comparing periods of presence and absence of AVHs within
      subject and "trait" studies comparing patients experiencing AVHs with patients
      without AVHs or healthy controls during tasks with verbal material. We set out to
      test the internal consistency and possible dissociations of the neural correlates
      of AVHs. We used activation likelihood estimation to perform quantitative meta
      analyses on brain regions reported in state and trait studies on AVHs to assess
      significant concordance across studies. State studies were associated with
      activation in bilateral inferior frontal gyrus, bilateral postcentral gyrus, and
      left parietal operculum. Trait studies on the other hand showed convergence of
      decreases in hallucinating subjects in left superior temporal gyrus, left middle
      temporal gyrus, anterior cingulate cortex, and left premotor cortex activity.
      Based on the clear dissociation of brain regions that show convergence across
      state in comparison to trait studies, we conclude that the state of experiencing
      AVHs is primarily related brain regions that have been implicated in speech
      production ie, Broca's area, whereas the general trait that makes humans prone to
      AVHs seems to be related to brain areas involved in auditory stimuli processing
      and speech perception, ie, auditory cortex.

PMID- 21177744
TI  - GPs' experiences of managing non-specific neck pain--a qualitative study.
AB  - BACKGROUND: Non-specific neck pain is a common complaint in general practice.
      Little is known about GPs' experiences of managing non-specific neck pain.
      OBJECTIVE: This qualitative study aims to elucidate GPs' opinions on the cause,
      diagnosis and management of non-specific neck pain and their experiences with
      patients suffering from this complaint. METHODS: A purposive sample of 19 German
      GPs was interviewed. Analysis was guided by predefined research questions and the
      general principles of grounded theory. We condensed the data into three key
      themes. RESULTS: The first key theme was the aetiology of neck pain and the
      patients' difficulty in accepting psychological explanations. GPs reported that
      their patients asked for definite and expensive forms of therapy. Though GPs
      preferred cost-efficient forms of therapy, fulfilment of patient expectations was
      the second key theme. Some felt that satisfying patient wishes may facilitate a
      trusting relationship so that psychological explanations or advice to adopt an
      active physical lifestyle would be accepted by patients more open-mindedly. The
      third key theme was the GPs' view on orthopaedic surgeons. Sometimes specialist
      diagnoses helped to reinforce the GPs findings. But many GPs had doubts as to
      whether an orthopaedic surgeon could tackle psychosomatic aspects of this
      complaint. CONCLUSIONS: In the case of non-specific neck pain, GPs often feel
      confronted with patients that demand dubious therapies and fail to consider
      psychological influences. The prescription of non-evidence-based therapies or
      referrals does not necessarily reflect a lack of knowledge but the GPs' strategic
      decision to improve the doctor-patient relationship.

PMID- 21177745
TI  - Follow-through of triage protocol.

PMID- 21177746
TI  - Donor cell origin of multiple myeloma occurring after allogeneic haematopoietic
      stem cell transplantation in a patient with refractory anaemia with ring
      sideroblast.
AB  - Post-transplant lymphoproliferative disorder (PTLD) is a rare but life
      threatening complication after solid organ and haematopoietic stem cell
      transplantation. A 40-year-old woman who was diagnosed as having refractory
      anaemia with ring sideroblast 6 years ago took an ABO mismatched, unrelated
      allogeneic haematopoietic stem cell transplantation (HSCT) from a 32-year-old
      healthy male donor. The bone marrow (BM) study was carried out because of
      progressing pancytopenia, serum biclonal gammopathy and a distorted ratio of
      serum level of free kappa and lambda light chain 138 days after HSCT. The BM
      examination showed an increased number of plasma cells (12% of total marrow
      cells) comprising mainly CD45-CD19-CD138+ malignant plasma cells with an
      immunoglobulin heavy-chain gene rearrangement. Conventional cytogenetics and
      molecular personal identification studies revealed that all BM cells were totally
      replaced by donor cells, thus indicating the donor cell origin of PTLD-multiple
      myeloma. The BM microenvironment of the recipient might be associated with the
      development of PTLD-multiple myeloma.

PMID- 21177747
TI  - Relationship between pathological features, HER2 protein expression and HER2 and
      CEP17 copy number in breast cancer: biological and methodological considerations.
AB  - AIMS: A few reports have assessed HER2 status in breast cancer by both dual-probe
      fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) in an
      unselected and consecutive fashion, but CEP17 and HER2 copy number were not
      evaluated separately in these studies. Therefore, the aim of this study was to
      perform FISH testing for HER2 in a large number of breast tumours, irrespective
      of the IHC scores, which were also determined in all cases. METHODS: Both FISH
      and IHC were applied to 200 tumours from 196 consecutive patients who underwent
      resection of primary breast cancer with the sentinel procedure and/or axillary
      dissection. Not only the ratio, but also mean HER2 and CEP17 copy number were
      determined and used in statistical analyses to evaluate relationships between
      FISH, IHC and clinicopathological features. RESULTS: The amplification status
      based solely on HER2 signals was 98% concordant with results of dual-probe FISH.
      In non-amplified tumours, the mean CEP17 and HER2 copy number correlated,
      possibly because of cell cycling. Amplified tumours were histopathologically more
      aggressive than non-amplified tumours, and features of aggressiveness increased
      with the mean HER2 copy number. In both amplified and non-amplified tumours, a
      gene dosage effect was observed: an increase in the mean HER2 copy number was
      associated with a higher IHC score. CONCLUSIONS: This working method and analysis
      enabled new insights to be obtained into the pathobiology of HER2 in breast
      cancer. The findings may be helpful in optimising the methodology of HER2
      testing.

PMID- 21177748
TI  - A comparative study of quantitative immunohistochemistry and quantum dot
      immunohistochemistry for mutation carrier identification in Lynch syndrome.
AB  - AIMS: Lynch Syndrome is caused by mutations in DNA mismatch repair (MMR) genes.
      Mutation carrier identification is facilitated by immunohistochemical detection
      of the MMR proteins MHL1 and MSH2 in tumour tissue and is desirable as
      colonoscopic screening reduces mortality. However, protein detection by
      conventional immunohistochemistry (IHC) is subjective, and quantitative
      techniques are required. Quantum dots (QDs) are novel fluorescent labels that
      enable quantitative multiplex staining. This study compared their use with
      quantitative 3,3'-diaminobenzidine (DAB) IHC for the diagnosis of Lynch Syndrome.
      METHODS: Tumour sections from 36 mutation carriers and six controls were
      obtained. These were stained with DAB on an automated platform using antibodies
      against MLH1 and MSH2. Multiplex QD immunofluorescent staining of the sections
      was performed using antibodies against MLH1, MSH2 and smooth muscle actin (SMA).
      Multispectral analysis of the slides was performed. The staining intensity of DAB
      and QDs was measured in multiple colonic crypts, and the mean intensity scores
      calculated. Receiver operating characteristic (ROC) curves of staining
      performance for the identification of mutation carriers were evaluated. RESULTS:
      For quantitative DAB IHC, the area under the MLH1 ROC curve was 0.872 (95% CI
      0.763 to 0.981), and the area under the MSH2 ROC curve was 0.832 (95% CI 0.704 to
      0.960). For quantitative QD IHC, the area under the MLH1 ROC curve was 0.812 (95%
      CI 0.681 to 0.943), and the area under the MSH2 ROC curve was 0.598 (95% CI 0.418
      to 0.777). CONCLUSIONS: Despite the advantage of QD staining to enable several
      markers to be measured simultaneously, it is of lower utility than DAB IHC for
      the identification of MMR mutation carriers. Automated DAB IHC staining and
      quantitative slide analysis may enable high-throughput IHC.

PMID- 21177749
TI  - Digital mammography in a screening programme and its implications for pathology:
      a comparative study.
AB  - AIMS: Most studies comparing full-field digital mammography (FFDM) with
      conventional screen-film mammography (SFM) have been radiology-based. The
      pathological implications of FFDM have received little attention in the
      literature, especially in the context of screening programmes. The primary
      objective of this retrospective study is to compare FFDM with SFM in a population
      based screening programme with regard to a number of pathological parameters.
      METHODS: During the study period, 107 818 women underwent screening mammograms
      with almost equal numbers obtained with each technique (49.9% with SFM vs 50.1%
      with FFDM). We compared SFM with FFDM using the following parameters: recall
      rate, diagnostic core biopsy rate, cancer detection rates, B3 rate, B4 rate,
      preoperative diagnostic rate for malignancy, positive predictive values and
      tumour characteristics. RESULTS: The recall rate was significantly higher with
      FFDM (4.21% vs 3.52%, p<0.0001). The overall cancer detection rate of 7.2 per
      1000 women screened with FFDM was also significantly higher than the rate of 6.2
      per 1000 women screened with SFM (p=0.04). The B3 rate in the SFM group was 1.3
      per 1000 women screened versus 2.5 per 1000 women screened in the FFDM group
      (p<0.001). The recall rate and cancer detection rates (overall, invasive and pure
      ductal carcinoma in situ) were all significantly higher with FFDM for lesions
      presenting as microcalcifications. CONCLUSIONS: The higher cancer detection rate
      with FFDM in this study was due to improved detection of microcalcifications.
      However, this was achieved at the cost of a higher recall rate and a higher B3
      rate, indicating that overtreatment may be problematic with digital mammography.

PMID- 21177750
TI  - A literary portrait of a case of Hodgkin lymphoma by Wilkie Collins?
AB  - In October 1859, 'The Queen of Hearts' was published by Wilkie Collins. This book
      is a collection of 10 short stories written by the protagonists (three retired
      brothers), in order to keep their niece (aka the queen of hearts) entertained,
      until the arrival of her fiance-to-be. The second story of the book, titled
      'Brother Griffith's story of the family secret,' narrates the death of a young
      girl who has a slow-growing deforming tumour on her neck. Even with the few
      clinical details provided by the literary description, the current report
      examines the possibility of Hodgkin lymphoma as a diagnosis, concluding that the
      option is not an unwise one.

PMID- 21177751
TI  - PML protein analysis using imaging flow cytometry.
AB  - Acute promyelocytic leukaemia (APML) can be promptly diagnosed by detecting
      abnormal diffuse staining patterns of PML bodies in abnormal promyelocytes using
      immunofluorescence microscopy. However, this technique is subjective, with low
      sensitivity. Using samples from 18 patients with acute myeloid leukaemia (AML)
      (including four with APML), the authors investigated whether imaging flow
      cytometry could be a viable alternative to this current technique and improve
      sensitivity levels. Bone marrow/peripheral blood cells were stained with an
      antibody to PML, and data were acquired on an ImageStream (Amnis Corporation,
      Seattle, Washington, USA). Using the modulation feature for data analysis, the
      authors demonstrated that this technique could successfully identify cases of
      APML. Imaging flow cytometry, by analysing greater numbers of cells and with the
      potential to include disease-specific antigens, increases the sensitivity of the
      current immunofluorescence technique. Imaging flow cytometry is an exciting
      technology that has many possible applications in the diagnosis of haematological
      malignancies, including the potential to integrate modalities.

PMID- 21177752
TI  - Carboxylesterase 1 (Ces1): from monocyte marker to major player.
AB  - There are few, if any, enzymes that have been studied by, and have importance in,
      so many and varied disciplines as has monocyte esterase/Ces 1. In this review its
      involvement in the fields of histochemistry, haematology, toxicology,
      pharmacology, therapeutics, and tumour cell killing, immune surveillance and
      malignant disease, is briefly described.

PMID- 21177753
TI  - Heel blood sampling in European neonatal intensive care units: compliance with
      pain management guidelines.
AB  - OBJECTIVE: To describe the use of heel blood sampling and non-pharmacological
      analgesia in a large representative sample of neonatal intensive care units
      (NICUs) in eight European countries, and compare their self-reported practices
      with evidence-based recommendations. METHODS: Information on use of heel blood
      sampling and associated procedures (oral sweet solutions, non-nutritive sucking,
      swaddling or positioning, topical anaesthetics and heel warming) were collected
      through a structured mail questionnaire. 284 NICUs (78% response rate)
      participated, but only 175 with >=50 very low birth weight admissions per year
      were included in this analysis. RESULTS: Use of heel blood sampling appeared
      widespread. Most units in the Netherlands, UK, Denmark, Sweden and France
      predominantly adopted mechanical devices, while manual lance was still in use in
      the other countries. The two Scandinavian countries and France were the most
      likely, and Belgium and Spain the least likely to employ recommended combinations
      of evidence-based pain management measures. CONCLUSIONS: Heel puncture is a
      common procedure in preterm neonates, but pain appears inadequately treated in
      many units and countries. Better compliance with published guidelines is needed
      for clinical and ethical reasons.

PMID- 21177754
TI  - Highly reactive anti-myelin oligodendrocyte glycoprotein antibodies differentiate
      demyelinating diseases from viral encephalitis in children.
AB  - BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) may be implicated in the
      immunopathogenesis of multiple sclerosis (MS) inducing demyelination in the
      animal model of MS. In adults reported anti-MOG antibody frequencies have been
      variable across a number of studies and can also be detected in controls.
      OBJECTIVE: To measure antibodies against MOG in paediatric patients with
      demyelinating disorders of the central nervous system and in controls. METHODS:
      Serum antibodies against MOG and myelin basic protein were measured by ELISA,
      flow cytometry (FACS) and in the liquid phase in 11 children with acute
      disseminated encephalomyelitis (ADEM), 22 children with MS, seven children with
      acute viral encephalitis and 13 healthy controls. The serostatus of Epstein-Barr
      virus (EBV) infections were assessed. RESULTS: Anti-MOG antibodies, measured
      either by ELISA or FACS were exclusively detected in children with demyelination.
      In ADEM these antibodies were highly reactive. Anti-MBP reactivity was detectable
      equally in all groups. The presence of either autoantibodies did not associate
      with EBV serostatus, age, gender or disease course. CONCLUSIONS: This study
      independently corroborates recently published results of seroprevalence and
      specificity of the assay. Due to their low sensitivity anti-MOG antibodies will
      not serve as disease-specific biomarkers, but could help to support the diagnosis
      of ADEM in difficult cases.

PMID- 21177755
TI  - -308 G > A of TNF-alpha gene promoter decreases the risk of multiple sclerosis: a
      meta-analysis.
AB  - BACKGROUND: Environmental and genetic factors are thought to be involved in the
      pathogenesis of multiple sclerosis (MS). Polymorphisms of tumor necrosis factor
      (TNF)-alpha -308 were implicated in MS risk in several case-control association
      studies. However, the studies have shown inconsistent results. OBJECTIVES: To
      address the association of G/A polymorphisms of TNF-alpha -308 with MS risk by
      meta-analysis. METHODS: Thirteen studies were included. Pooled odds ratios (ORs)
      together with 95% confidence intervals (CIs) were calculated. RESULTS: A total of
      1870 cases and 2769 controls were included in the meta-analysis. The pooled
      result indicated that -308 A allele is significantly associated with reduced risk
      of MS compared with -308 G allele (A vs. G, p=0.022). The same pattern of the
      result was also obtained in the contrasts of AA+ GA vs. GG (p=0.008) and GA vs.
      GG (p=0.007). For AA vs. GG or AA vs. GA + GG, no significant association was
      detected most likely caused by very low frequency or non-availability of
      homozygote genotype AA for all of the studies. CONCLUSIONS: TNF-alpha -308 A
      allele is associated with reduced risk of MS.

PMID- 21177756
TI  - Interferon-beta increases systemic BAFF levels in multiple sclerosis without
      increasing autoantibody production.
AB  - BACKGROUND: Treatment with interferon-beta (IFN-beta) increases B-cell activating
      factor of the TNF family (BAFF) expression in multiple sclerosis (MS), raising
      the concern that treatment of MS patients with IFN-beta may activate autoimmune B
      cells and stimulate the production of MS-associated autoantibodies. OBJECTIVE: To
      investigate whether BAFF levels are associated with disease severity/activity in
      untreated MS patients, and to assess the effect of IFN-beta therapy on
      circulating BAFF and anti-myelin basic protein (MBP) autoantibody levels.
      RESULTS: Twenty-three patients with relapsing-remitting MS (RRMS) were followed
      longitudinally from initiation of IFN-beta therapy. Their blood levels of BAFF
      correlated positively at baseline with the expanded disability status scale
      (p<0.009) and MS severity score (p<0.05), but not with disease activity as
      determined by the number of gadolinium-enhanced lesions. The patients were
      followed for up to 26 months, during which the BAFF levels remained elevated
      without association to increased disease activity. IFN-beta therapy caused an
      increase in plasma BAFF levels after both 3 and 6 months of therapy (p<0.002).
      However, an 11% decrease in IgM and a 33% decrease in IgG anti-MBP autoantibodies
      (p<0.09 and p<0.009, respectively) was observed after 6 months. CONCLUSION: Pre
      treatment BAFF levels correlate with high disability scores in MS, suggesting
      that high BAFF expression is a negative prognostic marker. Despite its known
      beneficial effects, IFN-beta therapy causes a sustained increase in plasma BAFF
      levels, which does not translate into increased levels of anti-MBP
      autoantibodies.

PMID- 21177757
TI  - An unopposed proinflammatory response is beneficial for survival in the oldest
      old. Results of the Leiden 85-plus Study.
AB  - The capacity to generate an efficient innate immune response is pivotal for
      survival. The objective of this study was to investigate innate immune function
      in relation to long-term survival in the oldest old. We measured ex vivo
      lipopolysaccharide-induced proinflammatory and antiinflammatory cytokine
      responses in 562 participants aged 85 years of the general population who were
      followed for mortality during 10 years. Compared with participants with a high
      proinflammatory and antiinflammatory response profile, 85 year olds with an
      overall low proinflammatory and antiinflammatory response had a significant
      higher mortality risk (hazard ratio: 1.79, 95% confidence interval: 1.29-2.50),
      whereas participants with a high proinflammatory and low antiinflammatory
      response had a survival benefit (hazard ratio: 0.74, 95% confidence interval:
      0.57-0.97). This benefit was even more pronounced in survivors past 90 years of
      age (hazard ratio: 0.50, 95% confidence interval: 0.26-0.96). In old age, the
      capacity to generate an unopposed proinflammatory innate immune response is
      predictive of long-term survival.

PMID- 21177758
TI  - CCAAT/enhancer-binding proteins (C/EBP)-alpha and -beta are essential for
      ovulation, luteinization, and the expression of key target genes.
AB  - LH activation of the epidermal growth factor receptor/RAS/ERK1/2 pathway is
      essential for ovulation and luteinization because granulosa cell (GC) depletion
      of ERK1/2 (ERK1/2(gc)(-/-) mice) renders mice infertile. As mediators of ERK1/2
      dependent GC differentiation, the CCAAT/enhancer-binding proteins, (C/EBP)alpha
      and C/EBPbeta, were also disrupted. Female Cebpb(gc)(-/-) mutant mice, but not
      Cebpa(gc)(-/-) mice, were subfertile whereas Cebpa/b(gc)(-/-) double-mutant
      females were sterile. Follicles failed to ovulate, ovaries were devoid of corpora
      lutea, luteal cell marker genes (Lhcgr, Prlr, Ptgfr, Cyp11a1, and Star) were
      absent, and serum progesterone levels were low. Microarray analyses identified
      numerous C/EBPalpha/beta target genes in equine chorionic gonadotropin (eCG)
      human (h)CG-treated mice. At 4 h post-hCG, a subset (19%) of genes altered in the
      Cebpa/b-depleted cells was also altered in ERK1/2-depleted cells; hence they are
      common effectors of ERK1/2. Additional genes down-regulated in the Cebpa/b
      depleted cells at 8 and 24 h post-hCG include known (Akr1b7, Runx2, Star, Saa3)
      and novel (Abcb1b, Apln, Igfbp4, Prlr, Ptgfr Timp4) C/EBP targets and effectors
      of luteal and vascular cell development. Bhmt, a gene controlling methionine
      metabolism and thought to be expressed exclusively in liver and kidney, was high
      in wild-type luteal cells but totally absent in Cebpa/b mutant cells. Because
      numerous genes potentially associated with vascular development were suppressed
      in the mutant cells, C/EBPalpha/beta appear to dictate the luteinization process
      by also controlling genes that regulate the formation of the extensive vascular
      network required to sustain luteal cells. Thus, C/EBPalpha/beta mediate the
      terminal differentiation of GCs during the complex process of luteinization.

PMID- 21177759
TI  - D440N mutation in the acid-labile subunit of insulin-like growth factor complexes
      inhibits secretion and complex formation.
AB  - The acid-labile subunit (ALS) regulates IGF bioavailability by forming
      heterotrimeric complexes with IGFs and IGF-binding protein-3 (IGFBP-3). A
      homozygous missense mutation (D440N) resulting in undetectable circulating levels
      of ALS with a concomitant reduction in IGF-I and IGFBP-3 has been reported to
      cause mild growth retardation. To understand how this particular mutation affects
      ALS circulating levels and IGF-transport function, we expressed recombinant ALS
      and its variants, D440N-ALS, T442A-ALS, and D440N/T442A-ALS, using adenovirus
      vectors. Compared with wild-type ALS, the secretion of D440N-ALS was 80% lower.
      The D440N mutation was proposed to generate an N-glycosylation site additional to
      the seven existing motifs in ALS. D440N-ALS appeared larger than ALS,
      attributable to N-linked glycans because deglycosylation with N-glycosidase F
      reduced both proteins to the same molecular mass. When ALS was incubated with IGF
      I and IGFBP-3, 70-80% of IGF-I was detected by gel-filtration chromatography in
      forms corresponding to the 150-kDa ternary complex. In contrast, when D440N-ALS
      was tested, less than 30% of IGF-I was found in high molecular mass complexes.
      Two other ALS variants mutated in the same putative glycosylation site,
      D440N/T442A-ALS and T442A-ALS, showed similar chromatographic profiles to wild
      type ALS. The D440N mutation in ALS generates a hyperglycosylated form with
      impaired secretion and complex formation, potentially leading to dysregulation of
      endocrine IGF, thus contributing to the growth retardation observed in the
      affected patient. This is the first study to explain how a natural mutation,
      D440N, in ALS impairs its function.

PMID- 21177761
TI  - Clinical validity of the Repeatable Battery for the Assessment of
      Neuropsychological Status among patients with schizophrenia in the Republic of
      Armenia.
AB  - There is considerable interest in Armenia toward advancing research and applying
      evidence-based practice in the treatment of schizophrenia. An area of research
      that has made little progress is the standardization of reliable and valid tests
      to measure cognitive functions. The aim of the present study was twofold. The
      first goal was to adapt the Repeatable Battery for the Assessment of
      Neuropsychological Status (RBANS) into Armenian. The second purpose was to
      examine the clinical validity of the Armenian-language RBANS in patients
      diagnosed with schizophrenia and healthy comparison controls. Seventy-seven
      patients with DSM IV TR diagnosis of schizophrenia or schizoaffective disorder,
      and 77 healthy individuals participated in the study. The cognitive performance
      of patients was compared with that of healthy controls and U.S. normative data.
      The Armenian-language RBANS demonstrated acceptable psychometric properties in
      terms of test validity and reliability. Relative to healthy controls, patients
      with schizophrenia exhibited impaired performance in all RBANS Index and Subtest
      tasks. Patients and comparison controls performed below the U.S. data with the
      greatest differences found in language and attention tasks. The present findings
      support that the Armenian-language RBANS is a good test for measuring cognitive
      functions in patients with schizophrenia and the general population. The
      performance differences between Armenian and U.S. samples highlight the
      limitation in using English-standardized normative data for cross-cultural
      studies. The results merit further investigation to disentangle cultural
      variations from cognitive disturbances.

PMID- 21177760
TI  - Regulation of Sertoli-germ cell adhesion and sperm release by FSH and
      nonclassical testosterone signaling.
AB  - Testosterone and FSH act in synergy to produce the factors required to maximize
      the production of spermatozoa and male fertility. However, the molecular
      mechanisms by which these hormones support spermatogenesis are not well
      established. Recently, we identified a nonclassical mechanism of testosterone
      signaling in cultured rat Sertoli cells. We found that testosterone binding to
      the androgen receptor recruits and activates Src tyrosine kinase. Src then causes
      the activation of the epidermal growth factor receptor, which results in the
      phosphorylation and activation of the ERK MAPK and the cAMP response element
      binding protein transcription factor. In this report, we find that FSH inhibits
      testosterone-mediated activation of ERK and the MAPK pathway in Sertoli cells via
      the protein kinase A-mediated inhibition of Raf kinase. In addition, FSH, as well
      as inhibitors of Src and ERK kinase activity, reduced germ cell attachment to
      Sertoli cells in culture. Using pathway-specific androgen receptor mutants we
      found that the nonclassical pathway is required for testosterone-mediated
      increases in germ cell attachment to Sertoli cells. Studies of seminiferous
      tubule explants determined that Src kinase, but not ERK kinase, activity is
      required for the release of sperm from seminiferous tubule explants. These
      findings suggest the nonclassical testosterone-signaling pathway acts via Src and
      ERK kinases to facilitate the adhesion of immature germ cells to Sertoli cells
      and through Src to permit the release of mature spermatozoa. In contrast, FSH
      acts to limit testosterone-mediated ERK kinase activity and germ cell attachment.

PMID- 21177762
TI  - Executive function profile of Chinese boys with attention-deficit hyperactivity
      disorder: different subtypes and comorbidity.
AB  - This study examined the executive function (EF) profile of Chinese boys with
      attention-deficit hyperactivity disorder (ADHD) using a large sample. Executive
      function performance within the ADHD subtypes and the effects of comorbidity were
      also investigated. Five hundred Chinese boys (375 with ADHD and 125 controls)
      aged 6-15 completed a battery of EF tests. Boys with all types of ADHD performed
      worse in all of the EF tests than age- and intelligence quotient-matched healthy
      controls. The boys with the inattention ADHD subtype and the combined subtype
      showed similar impairments across different EF tasks, whereas the boys with the
      hyperactive-impulsive ADHD subtype primarily displayed deficits in theory of mind
      and visual memory. Comorbid oppositional defiant disorder/conduct disorder had no
      additional influence on the EF characteristics of the boys with ADHD only,
      whereas comorbid learning disorder increased the severity of inhibition and
      shifting impairments.

PMID- 21177764
TI  - Combination mTOR and IGF-1R inhibition: phase I trial of everolimus and
      figitumumab in patients with advanced sarcomas and other solid tumors.
AB  - PURPOSE: Preclinical models demonstrate synergistic antitumor activity with
      combination blockade of mTOR and IGF-1R signaling. We aimed to determine the
      safety, tolerability, and recommended phase II dose (RP2D) of the combination of
      figitumumab, a fully human IgG(2) anti-insulin-like growth factor-1 receptor (IGF
      1R) monoclonal antibody (Pfizer) and the mTOR inhibitor, everolimus (Novartis).
      Pharmacokinetics and preliminary antitumor effects of the combination were
      evaluated. EXPERIMENTAL DESIGN: Phase I trial in patients with advanced sarcomas
      and other solid tumors. Initial cohort combined full phase 2 dose figitumumab (20
      mg/kg IV every 21 days) with full dose everolimus (10 mg orally once daily).
      Intercohort dose de-escalation was planned for unacceptable toxicities. Dose
      modifications were allowed beyond cycle 1. RESULTS: No DLTs were observed in the
      initial cohort during cycle one, therefore full dose figitumumab and everolimus
      was declared the RP2D. In total, 21 patients were enrolled on study. Most
      toxicities were grade 1 or 2, and were similar to reported toxicities of the
      single agents. Mucositis was the most frequently observed grade 3 toxicity.
      Median time on study was 104 days (range 17-300). Of 18 patients evaluable for
      response, best response was partial response in 1 patient with malignant solitary
      fibrous tumor and, stable disease in 15 patients. There were no apparent
      pharmacokinetic interactions between everolimus and figitumumab. CONCLUSIONS:
      Combination figitumumab plus everolimus at full doses appears safe and well
      tolerated with no unexpected toxicities. Dose reductions in everolimus may be
      required after prolonged drug administration. This regimen exhibits interesting
      antitumor activity warranting further investigation.

PMID- 21177763
TI  - High IGF-IR activity in triple-negative breast cancer cell lines and tumorgrafts
      correlates with sensitivity to anti-IGF-IR therapy.
AB  - PURPOSE: We previously reported an insulin-like growth factor (IGF) gene
      expression signature, based on genes induced or repressed by IGF-I, which
      correlated with poor prognosis in breast cancer. We tested whether the IGF
      signature was affected by anti-IGF-I receptor (IGF-IR) inhibitors and whether the
      IGF signature correlated with response to a dual anti-IGF-IR/insulin receptor
      (InsR) inhibitor, BMS-754807. EXPERIMENTAL DESIGN: An IGF gene expression
      signature was examined in human breast tumors and cell lines and changes were
      noted following treatment of cell lines or xenografts with anti-IGF-IR antibodies
      or tyrosine kinase inhibitors. Sensitivity of cells to BMS-754807 was correlated
      with levels of the IGF signature. Human primary tumorgrafts were analyzed for the
      IGF signature and IGF-IR levels and activity, and MC1 tumorgrafts were treated
      with BMS-754807 and chemotherapy. RESULTS: The IGF gene expression signature was
      reversed in three different models (cancer cell lines or xenografts) treated with
      three different anti-IGF-IR therapies. The IGF signature was present in triple
      negative breast cancers (TNBC) and TNBC cell lines, which were especially
      sensitive to BMS-754807, and sensitivity was significantly correlated to the
      expression of the IGF gene signature. The TNBC primary human tumorgraft MC1
      showed high levels of both expression and activity of IGF-IR and IGF gene
      signature score. Treatment of MC1 with BMS-754807 showed growth inhibition and,
      in combination with docetaxel, tumor regression occurred until no tumor was
      palpable. Regression was associated with reduced proliferation, increased
      apoptosis, and mitotic catastrophe. CONCLUSIONS: These studies provide a clear
      biological rationale to test anti-IGF-IR/InsR therapy in combination with
      chemotherapy in patients with TNBC.

PMID- 21177765
TI  - Copy number alterations in urothelial carcinomas: their clinicopathological
      significance and correlation with DNA methylation alterations.
AB  - The aim of this study was to clarify the genetic backgrounds underlying the
      clinicopathological characteristics of urothelial carcinomas (UCs). Array
      comparative genomic hybridization analysis using a 244K oligonucleotide array was
      performed on 49 samples of UC tissue. Losses of 2q33.3-q37.3, 4p15.2-q13.1 and
      5q13.3-q35.3 and gains of 7p11.2-q11.23 and 20q13.12-q13.2 were correlated with
      higher histological grade, and gain of 7p21.2-p21.12 was correlated with deeper
      invasion. Losses of 6q14.1-q27 and 17p13.3-q11.1 and gains of 19q13.12-q13.2 and
      20q13.12-q13.33 were correlated with lymph vessel involvement. Loss of 16p12.2
      p12.1 and gain of 3q26.32-q29 were correlated with vascular involvement. Losses
      of 5q14.1-q23.1, 6q14.1-q27, 8p22-p21.3, 11q13.5-q14.1 and 15q11.2-q22.2 and
      gains of 7p11.2-q11.22 and 19q13.12-q13.2 were correlated with the development of
      aggressive non-papillary UCs. Losses of 1p32.2-p31.3, 10q11.23-q21.1 and 15q21.3
      were correlated with tumor recurrence. Unsupervised hierarchical clustering
      analysis based on copy number alterations clustered UCs into three subclasses:
      copy number alterations associated with genome-wide DNA hypomethylation, regional
      DNA hypermethylation on C-type CpG islands and genome-wide DNA hypo- and
      hypermethylation were accumulated in clusters A, B(1) and B(2), respectively.
      Tumor-related genes that may encode therapeutic targets and/or indicators useful
      for the diagnosis and prognostication of UCs should be explored in the above
      regions. Both genetic and epigenetic events appear to accumulate during
      urothelial carcinogenesis, reflecting the clinicopathological diversity of UCs.

PMID- 21177766
TI  - P21-activated protein kinase (PAK2)-mediated c-Jun phosphorylation at 5 threonine
      sites promotes cell transformation.
AB  - The oncoprotein c-Jun is one of the components of the activator protein-1 (AP-1)
      transcription factor complex. AP-1 regulates the expression of many genes and is
      involved in a variety of biological functions such as cell transformation,
      proliferation, differentiation and apoptosis. AP-1 activates a variety of tumor
      related genes and therefore promotes tumorigenesis and malignant transformation.
      Here, we found that epidermal growth factor (EGF) induces phosphorylation of c
      Jun by P21-activated kinase (PAK) 2. Our data showed that PAK2 binds and
      phosphorylates c-Jun at five threonine sites (Thr2, Thr8, Thr89, Thr93 and
      Thr286) in vitro and ex vivo. Knockdown of PAK2 in JB6 Cl41 (P+) cells had no
      effect on c-Jun phosphorylation at Ser63 or Ser73 but resulted in decreases in
      EGF-induced anchorage-independent cell transformation, proliferation and AP-1
      activity. Mutation at all five c-Jun threonine sites phosphorylated by PAK2
      decreased the transforming ability of JB6 cells. Knockdown of PAK2 in SK-MEL-5
      melanoma cells also decreased colony formation, proliferation and AP-1 activity.
      These results indicated that PAK2/c-Jun signaling plays an important role in EGF
      induced cell proliferation and transformation.

PMID- 21177767
TI  - IRIZIO: a novel gene cooperating with PAX3-FOXO1 in alveolar rhabdomyosarcoma
      (ARMS).
AB  - Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children with an
      annual incidence of five new cases per million. Alveolar rhabdomyosarcoma (ARMS)
      is characterized by the t(2;13) or t(1;13) chromosomal translocations, which
      generate the PAX3-FOXO1 or PAX7-FOXO1 fusion genes, respectively. The oncogenic
      activity of PAX3-FOXO1 has been demonstrated in vitro and in vivo, yet expression
      of the fusion protein alone in primary myoblasts or a mouse model is insufficient
      for tumorigenic transformation. To identify genes cooperating with PAX3-FOXO1 in
      ARMS tumorigenesis, we generated a retroviral complementary DNA (cDNA) expression
      library from the Rh30 ARMS cell line. Arf-/- myoblasts expressing PAX3-FOXO1 and
      the retroviral cDNA library rapidly formed tumors after subcutaneous injection
      into NOD-SCID mice. Tumors formed by Arf-/-/PAX3-FOXO1/MarX-library myoblasts
      contained an unknown cDNA, encoding the C-terminus of the Homo sapiens
      hypothetical protein, FLJ10404, herein named IRIZIO. Expression of full length
      IRIZIO cDNA also cooperated with PAX3-FOXO1 in the transformation of Arf-/-
      myoblasts. Given that IRIZIO is expressed at increased levels in RMS, it might
      contribute to rhabdomyosarcomagenesis in humans.

PMID- 21177768
TI  - Guggulsterone (GS) inhibits smokeless tobacco and nicotine-induced NF-kappaB and
      STAT3 pathways in head and neck cancer cells.
AB  - Understanding the molecular pathways perturbed in smokeless tobacco- (ST)
      associated head and neck squamous cell carcinoma (HNSCC) is critical for
      identifying novel complementary agents for effective disease management.
      Activation of nuclear factor-kappaB (NF-kappaB) and cyclooxygenase-2 (COX-2) was
      reported in ST-associated HNSCC by us [Sawhney,M. et al. (2007) Expression of NF
      kappaB parallels COX-2 expression in oral precancer and cancer: association with
      smokeless tobacco. Int. J. Cancer, 120, 2545-2556]. In search of novel agents for
      treatment of HNSCC, we investigated the potential of guggulsterone (GS),
      (4,17(20)-pregnadiene-3,16-dione), a biosafe nutraceutical, in inhibiting ST- and
      nicotine-induced activation of NF-kappaB and signal transducer and activator of
      transcription (STAT) 3 pathways in HNSCC cells. GS inhibited the activation of NF
      kappaB and STAT3 proteins in head and neck cancer cells. This inhibition of NF
      kappaB by GS resulted from decreased phosphorylation and degradation of nuclear
      factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha the
      inhibitory subunit of NF-kappaB. Importantly, treatment of HNSCC cells with GS
      abrogated both ST- and nicotine-induced nuclear activation of NF-kappaB and
      pSTAT3 proteins and their downstream targets COX-2 and vascular endothelial
      growth factor. Furthermore, GS treatment decreased the levels of ST- and nicotine
      induced secreted interleukin-6 in culture media of HNSCC cells. In conclusion,
      our findings demonstrated that GS treatment abrogates the effects of ST and
      nicotine on activation of NF-kappaB and STAT3 pathways in HNSCC cells that
      contribute to inflammatory and angiogenic responses as well as its progression
      and metastasis. These findings provide a biologic rationale for further clinical
      investigation of GS as an effective complementary agent for inhibiting ST-induced
      head and neck cancer.

PMID- 21177769
TI  - Policy development and implementation in health promotion--from theory to
      practice: the ADEPT model.
AB  - There is a growing interest among health promotion researchers to better
      understand and influence the policy process. However, at this point in time,
      theoretical concepts enabling researchers to do so are still rare and underused,
      suggesting a need for new, easy-to-use concepts to explain successes or failures
      of health promotion policies. This article presents the ADEPT (Analysis of
      Determinants of Policy Impact) approach, which aims to explain and influence
      policy development and policy impact implementation with four determinants:
      goals, obligations, resources and opportunities. ADEPT provides a detailed
      operationalization for both quantitative and qualitative use. An empirical test
      of the ADEPT model using a quantitative survey of 719 policy-makers from four
      health promotion policy fields and six European nations indicated that both
      policy outputs and policy outcomes are influenced by the four determinants. The
      approach has, in the meantime, been successfully utilized to analyze and initiate
      policy development in a number of health promotion projects. Despite a number of
      limitations, ADEPT provides an easy-to-use, theory-based and parsimonious tool
      for understanding and influencing policy processes in health promotion. Moreover,
      as it identifies potential 'levers of influence' and can easily be connected to
      existing methods of community development or capacity building, it is a
      particularly powerful tool for policy development.

PMID- 21177770
TI  - A translational research intervention to reduce screen behaviours and promote
      physical activity among children: Switch-2-Activity.
AB  - Translational or implementation research that assesses the effectiveness of
      strategies to promote health behaviours among children that have been previously
      tested under 'ideal' conditions is rarely reported. Switch-2-Activity aimed to
      examine the effectiveness of an abbreviated programme delivered by teachers
      targeting children's television viewing, computer use, physical activity and
      potential mediators of behaviour change. Fifteen schools from disadvantaged areas
      in Melbourne, Australia agreed to participate in the study (43% school-level
      response rate). Out of the 1566 Grades 5 and 6 (9-12 year old) children invited
      to take part in the study, 1048 (67% response rate) provided informed consent.
      Schools were randomized to either an intervention or wait-list control condition.
      Teachers delivered six lessons, which included strategies such as self
      monitoring, behavioural contracting and budgeting of screen time. Children
      completed a self-report survey at baseline and post-intervention examining screen
      based behaviours, physical activity, self-efficacy and behavioural capability.
      Teachers reported implementation of and attitudes to the programme. Seventy-one
      per cent of teachers delivered at least four of the six lessons. Most teachers
      reported that the materials were easy to follow and deliver; however, many
      teachers reported modifying the materials in some way. Among boys, there were
      favourable small intervention effects on weekend screen time [(coefficient = 
      0.62, 95% 95% confidence interval: -1.15, -0.10, p = 0.020)]. The intervention
      also had significant positive effects on children's self-efficacy for reducing
      television viewing and on behavioural capability (television viewing styles).
      Future studies that assess the translation of efficacious programmes and that
      test whether such programmes are equally effective in different settings (e.g. in
      the family setting) are urgently required.

PMID- 21177771
TI  - Acute functional neurotoxicity of lanthanum(III) in primary cortical networks.
AB  - Because of its diverse physical and chemical properties, lanthanum has been used
      in various industrial and medical fields. However, until recently, its effects at
      the cellular and molecular level had hardly been investigated. Using primary
      cortical networks grown on microelectrode array neurochips, we investigated the
      acute functional neurotoxicity of lanthanum(III) chloride (LaCl(3)). Lanthanum
      caused a biphasic concentration-dependent decline in network activity resulting
      in a complete cessation of the activity at 3mM LaCl(3). However, the networks'
      oscillatory behavior and synchronicity between neurons remained unaffected until
      activity loss. The spike activity diminished at half effective concentration
      values for the two phases of 117 nM and 763 MUM LaCl(3) corresponding to 16 ng/ml
      and 10.6 MUg/ml lanthanum, respectively. Furthermore, under the experimental
      conditions, LaCl(3) did not affect voltage-dependent ion channels contributing to
      the shape and amplitude of the action potential. Further similarity analysis by
      pattern recognition exposed significant similarities of the activity changes
      caused by LaCl(3) to those induced by phenobarbital, gamma-aminobutyric acid, and
      the gap junction blocker carbenoxolone and sodium propionate. Overall, this study
      demonstrates inhibitory and potentially sedative toxicological effects of
      lanthanum(III) ions at concentrations comparable to the plasma concentrations
      observed in patients with kidney disease being treated with lanthanum carbonate
      for hyperphosphatemia. Therefore, given the lack of proof that the blood-brain
      barrier is completely impermeable in uremic patients and lanthanum cannot cross,
      caution is warranted.

PMID- 21177772
TI  - Cardiotoxicity associated with targeting kinase pathways in cancer.
AB  - Cardiotoxicity, also referred to as drug-induced cardiac injury, is an issue
      associated with the use of some small-molecule kinase inhibitors and antibody
      based therapies targeting signaling pathways in cancer. Although these drugs have
      had a major impact on cancer patient survival, data have implicated kinase
      targeting agents such as sunitinib, imatinib, trastuzumab, and sorafenib in
      adversely affecting cardiac function in a subset of treated individuals. In many
      cases, adverse cardiac events in the clinic were not anticipated based on
      preclinical safety evaluation of the molecule. In order to support the
      development of efficacious and safe kinase inhibitors for the treatment of cancer
      and other indications, new preclinical approaches and screens are required to
      predict clinical cardiotoxicity. Laboratory investigations into the underlying
      molecular mechanisms of heart toxicity induced by these molecules have identified
      potentially common themes including mitochondrial perturbation and modulation of
      adenosine monophosphate-activated protein kinase activity. Studies characterizing
      cardiac-specific kinase knockout mouse models have developed our understanding of
      the homeostatic role of some of these signaling mediators in the heart.
      Therefore, when considering kinases as potential future targets or when examining
      secondary pharmacological interactions of novel kinase inhibitors, these models
      may help to inform us of the potential adverse cardiac effects in the clinic.

PMID- 21177773
TI  - Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide
      association study.
AB  - Acetaminophen is the leading cause of acute hepatic failure in many developed
      nations. Acetaminophen hepatotoxicity is mediated by the reactive metabolite N
      acetyl-p-benzoquinonimine (NAPQI). We performed a "discovery" genome-wide
      association study using a cell line-based model system to study the possible
      contribution of genomics to NAPQI-induced cytotoxicity. A total of 176
      lymphoblastoid cell lines from healthy subjects were treated with increasing
      concentrations of NAPQI. Inhibiting concentration 50 values were determined and
      were associated with "glutathione pathway" gene single nucleotide polymorphisms
      (SNPs) and genome-wide basal messenger RNA expression, as well as with 1.3
      million genome-wide SNPs. A group of SNPs in linkage disequilibrium on chromosome
      3 was highly associated with NAPQI toxicity. The p value for rs2880961, the SNP
      with the lowest p value, was 1.88 * 10(-7). This group of SNPs mapped to a "gene
      desert," but chromatin immunoprecipitation assays demonstrated binding of several
      transcription factor proteins including heat shock factor 1 (HSF1) and HSF2, at
      or near rs2880961. These chromosome 3 SNPs were not significantly associated with
      variation in basal expression for any of the genome-wide genes represented on the
      Affymetrix U133 Plus 2.0 GeneChip. We have used a cell line-based model system to
      identify a SNP signal associated with NAPQI cytotoxicity. If these observations
      are validated in future clinical studies, this SNP signal might represent a
      potential biomarker for risk of acetaminophen hepatotoxicity. The mechanisms
      responsible for this association remain unclear.

PMID- 21177774
TI  - The new toxicology of sophisticated materials: nanotoxicology and beyond.
AB  - It has long been recognized that the physical form of materials can mediate their
      toxicity--the health impacts of asbestiform materials, industrial aerosols, and
      ambient particulate matter are prime examples. Yet over the past 20 years,
      toxicology research has suggested complex and previously unrecognized
      associations between material physicochemistry at the nanoscale and biological
      interactions. With the rapid rise of the field of nanotechnology and the design
      and production of increasingly complex nanoscale materials, it has become ever
      more important to understand how the physical form and chemical composition of
      these materials interact synergistically to determine toxicity. As a result, a
      new field of research has emerged--nanotoxicology. Research within this field is
      highlighting the importance of material physicochemical properties in how dose is
      understood, how materials are characterized in a manner that enables quantitative
      data interpretation and comparison, and how materials move within, interact with,
      and are transformed by biological systems. Yet many of the substances that are
      the focus of current nanotoxicology studies are relatively simple materials that
      are at the vanguard of a new era of complex materials. Over the next 50 years,
      there will be a need to understand the toxicology of increasingly sophisticated
      materials that exhibit novel, dynamic and multifaceted functionality. If the
      toxicology community is to meet the challenge of ensuring the safe use of this
      new generation of substances, it will need to move beyond "nano" toxicology and
      toward a new toxicology of sophisticated materials. Here, we present a brief
      overview of the current state of the science on the toxicology of nanoscale
      materials and focus on three emerging toxicology-based challenges presented by
      sophisticated materials that will become increasingly important over the next 50
      years: identifying relevant materials for study, physicochemical
      characterization, and biointeractions.

PMID- 21177775
TI  - The evolution of bioinformatics in toxicology: advancing toxicogenomics.
AB  - As one reflects back through the past 50 years of scientific research, a
      significant accomplishment was the advance into the genomic era. Basic research
      scientists have uncovered the genetic code and the foundation of the most
      fundamental building blocks for the molecular activity that supports biological
      structure and function. Accompanying these structural and functional discoveries
      is the advance of techniques and technologies to probe molecular events, in time,
      across environmental and chemical exposures, within individuals, and across
      species. The field of toxicology has kept pace with advances in molecular study,
      and the past 50 years recognizes significant growth and explosive understanding
      of the impact of the compounds and environment to basic cellular and molecular
      machinery. The advancement of molecular techniques applied in a whole-genomic
      capacity to the study of toxicant effects, toxicogenomics, is no doubt a
      significant milestone for toxicological research. Toxicogenomics has also
      provided an avenue for advancing a joining of multidisciplinary sciences
      including engineering and informatics in traditional toxicological research. This
      review will cover the evolution of the field of toxicogenomics in the context of
      informatics integration its current promise, and limitations.

PMID- 21177776
TI  - Changes in dietary iron exacerbate regional brain manganese accumulation as
      determined by magnetic resonance imaging.
AB  - Manganese (Mn) is an essential metal required for normal homeostasis. Humans
      chronically exposed to high Mn levels, however, may exhibit psychomotor signs
      secondary to increased brain Mn. As Mn and iron (Fe) share several cellular
      membrane transporters, decreased Fe levels resulting from Fe deficiency or anemia
      lead to increased brain Mn deposition. Conversely, decreased Mn levels are
      associated with abnormal brain Fe accumulation. To reduce potential Mn toxicity
      resulting from brain Mn accumulation, we proposed that increased dietary Fe would
      attenuate brain Mn deposition. To test this hypothesis, three groups of Sprague
      Dawley rats were injected weekly (14 weeks) with Mn (3 mg/kg) and fed normal Fe
      (TX), Fe-supplemented (FeS), or Fe-deficient (FeD) chow. Control (CN) rats
      received normal dietary Fe and saline injections. Using magnetic resonance
      imaging, rats were imaged biweekly for 14 weeks to qualitatively monitor brain Mn
      and Fe accumulation. Both FeS and FeD had greater brain Mn deposition than TX
      rats. By week 3, R(1) values, which correlate with Mn deposition, were
      statistically significantly increased (p < 0.05) in brain stem, cerebellum,
      cortex, midbrain, and striatum compared with CN or TX animals. By week 14, R(1)
      values for all brain regions in FeS and FeD animals were statistically
      significantly increased (p < 0.05). By the end of the study, similar results were
      obtained for R(2) values, a marker of Fe accumulation. These data suggest that Fe
      supplementation does not effectively protect and may even exacerbate brain Mn
      accumulation in mammals subchronically exposed to Mn.

PMID- 21177777
TI  - Long-term outcomes of fractionated stereotactic radiotherapy for intracranial
      skull base benign meningiomas in single institution.
AB  - OBJECTIVE: To investigate the outcome of linac-based fractionated stereotactic
      radiotherapy over the last 10 years for intracranial skull base benign
      meningiomas in patients who were inoperable, who had residual tumors with some
      components of high mitotic index after surgery and who experienced relapse of the
      tumor. METHODS: Twenty-seven patients with intracranial skull base benign
      meningiomas treated with fractionated stereotactic radiotherapy were
      retrospectively reviewed. Twenty-seven cases were diagnosed as benign meningiomas
      on pathological (17 cases) or radiological (10 cases) examination. The median
      follow-up time was 90 months after initial treatment and 63 months after
      fractionated stereotactic radiotherapy. The median biological equivalent dose
      calculated using an alpha/beta ratio of 2.0 Gy was 82.0 Gy (range, 60-106 Gy).
      RESULTS: The 5-year overall survival was 95.7 (95% confidence interval: 87.3
      100)% after initial treatment and 96.2 (88.8-100)% after fractionated
      stereotactic radiotherapy. The 5-year overall survival and local control rate of
      patients who received fractionated stereotactic radiotherapy alone were both
      100%. The 5-year progression-free survival and local control rate after
      fractionated stereotactic radiotherapy were all 100% with a tumor volume of <9.1
      cc and 68.2 (37.2-99.2) and 75.8 (45.2-100)% for the tumors 9.1 cc, respectively.
      The difference was significant in progression-free survival (P = 0.022) and local
      control rate (P = 0.044). The local control rate was significantly worse in
      patients who received fractionated stereotactic radiotherapy for relapsed tumors
      (P = 0.01). No late radiation damage was observed in the follow-up period.
      CONCLUSIONS: The long-term outcome suggests that fractionated stereotactic
      radiotherapy is a safe and effective treatment for intracranial skull base benign
      meningioma, especially for those who have tumors <9.1 cc or would receive
      fractionated stereotactic radiotherapy with or without surgery as the initial
      treatment.

PMID- 21177778
TI  - Glomerular sclerosis is prevented during urinary tract obstruction due to
      podocyte protection.
AB  - Urine outflow obstruction activates a variety of profibrotic factors, including
      the intrarenal renin-angiotensin system. However, the obstruction also nullifies
      the transmural hydraulic pressure difference across the glomerular capillary
      wall, an established inducer of glomerulosclerosis. In the present study, we
      investigated whether, and by what mechanism, urine outflow obstruction affects
      the process of progressive glomerulosclerosis. For this purpose, we tested the
      effect of unilateral ureteral obstruction (UUO) of 7 days duration in two
      distinct mouse models of glomerulosclerosis. In the human immunodeficiency virus
      (HIV) nephropathy model, where HIV-1 genes are selectively expressed in podocytes
      and develop progressive podocyte damage and glomerulosclerosis, UUO protected
      against sclerosis with preservation of podocytes morphologically and
      immunohistochemically. In contrast, the nonobstructed contralateral kidneys of
      these mice, as well as sham-operated HIV-1 mouse kidneys, developed severe
      podocyte injury and glomerulosclerosis. The protection against glomerulosclerosis
      imparted by ureteral obstruction was also documented in the NEP25 model of
      podocyte injury, in which a single injection of immunotoxin, LMB2, triggers
      selective podocyte injury followed by glomerulosclerosis, both of which were
      protected by UUO. Notably, intervention with an angiotensin II type 1 receptor
      antagonist provided only a partial protective effect in each of the models. These
      results demonstrate that urine outflow obstruction protects the glomerulus from
      progressive sclerosis. The results further reveal that this protection occurs at
      a very early stage of the pathologic process, namely, damage of podocytes.

PMID- 21177779
TI  - Flow regulation of collecting duct endothelin-1 production.
AB  - Collecting duct (CD) endothelin-1 (ET-1) is an important autocrine inhibitor of
      CD Na(+) reabsorption. Salt loading is thought to increase CD ET-1 production;
      however, definitive evidence of this, as well as understanding of the mechanisms
      transducing this effect, is lacking. Tubule fluid flow increases in response to
      Na(+) loading; hence, we studied flow modulation of CD ET-1 production. Three
      days of a high-salt diet increased mouse and rat inner medullary CD (IMCD) ET-1
      mRNA expression. Acute furosemide infusion increased urinary ET-1 excretion in
      anesthetized rats. Primary cultures of mouse or rat IMCD detached in response to
      flow using a closed perfusion chamber, consequently a CD cell line (mpkCCDcl4)
      was examined. Flow increased ET-1 mRNA at shear stress rates exceeding 1
      dyne/cm(2), with the maximal effect seen between 2 and 10 dyne/cm(2). Induction
      of ET-1 mRNA was first evident after 1 h, and most apparent after 2 h, of flow.
      Inhibition of calmodulin or dihydropyridine-sensitive Ca(2+) channels did not
      alter the flow response; however, chelation of intracellular Ca(2+) or removal of
      extracellular Ca(2+) largely prevented flow-stimulated ET-1 mRNA accumulation.
      Downregulation of protein kinase C (PKC) using phorbol 12-myristate 13-acetate,
      or PKC inhibition with calphostin C, markedly reduced flow-stimulated ET-1 mRNA
      levels. Flow-stimulated ET-1 mRNA accumulation was abolished by inhibition of
      phospholipase C (PLC). Taken together, these data indicate that flow increases CD
      ET-1 production and this is dependent on extracellular and intracellular Ca(2+),
      PKC, and PLC. These studies suggest a novel pathway for coupling alterations in
      extracellular fluid volume to CD ET-1 production and ultimately control of CD
      Na(+) reabsorption.

PMID- 21177780
TI  - ASARM peptides: PHEX-dependent and -independent regulation of serum phosphate.
AB  - Increased acidic serine aspartate-rich MEPE-associated motif (ASARM) peptides
      cause mineralization defects in X-linked hypophosphatemic rickets mice (HYP) and
      "directly" inhibit renal phosphate uptake in vitro. However, ASARM peptides also
      bind to phosphate-regulating gene with homologies to endopeptidases on the X
      chromosome (PHEX) and are a physiological substrate for this bone-expressed,
      phosphate-regulating enzyme. We therefore tested the hypothesis that circulating
      ASARM peptides also "indirectly" contribute to a bone-renal PHEX-dependent
      hypophosphatemia in normal mice. Male mice (n = 5; 12 wk) were fed for 8 wk with
      a normal phosphorus and vitamin D(3) diet (1% P(i) diet) or a reduced phosphorus
      and vitamin D(3) diet (0.1% P(i) diet). For the final 4 wk, transplantation of
      mini-osmotic pumps supplied a continuous infusion of either ASARM peptide (5
      mg.day(-1).kg(-1)) or vehicle. HYP, autosomal recessive hypophosphatemic rickets
      (ARHR), and normal mice (no pumps or ASARM infusion; 0.4% P(i) diet) were used in
      a separate experiment designed to measure and compare circulating ASARM peptides
      in disease and health. ASARM treatment decreased serum phosphate concentration
      and renal phosphate cotransporter (NPT2A) mRNA with the 1% P(i) diet. This was
      accompanied by a twofold increase in serum ASARM and 1,25-dihydroxy vitamin D(3)
      [1,25 (OH)(2)D(3)] levels without changes in parathyroid hormone. For both diets,
      ASARM-treated mice showed significant increases in serum fibroblast growth factor
      23 (FGF23; +50%) and reduced serum osteocalcin (-30%) and osteopontin (-25%).
      Circulating ASARM peptides showed a significant inverse correlation with serum
      P(i) and a significant positive correlation with fractional excretion of
      phosphate. We conclude that constitutive overexpression of ASARM peptides plays a
      "component" PHEX-independent part in the HYP and ARHR hypophosphatemia. In
      contrast, with wild-type mice, ASARM peptides likely play a bone PHEX-dependent
      role in renal phosphate regulation and FGF23 expression. They may also coordinate
      FGF23 expression by competitively modulating PHEX/DMP1 interactions and thus bone
      renal mineral regulation.

PMID- 21177781
TI  - Survival and long-term health and cognitive outcomes after low-grade glioma.
AB  - Long-term morbidity for children with low-grade glioma (LGG) requires exposure
      specific characterization. Overall survival (OS) and progression-free survival
      (PFS) were estimated for 361 children diagnosed with LGG between 1985 and 2007 at
      a single institution. Five-year survivors (n = 240) received risk-based clinical
      assessment. Cumulative incidence of late effects 15 years from diagnosis were
      estimated. Risk factors for adverse health were identified using Fine and Gray's
      approach to Cox's proportional hazards model, accounting for death as a competing
      risk. OS at 15 years was 86% (95% confidence interval [CI] 82%-90%), and PFS was
      55% (95% CI 51%-58%). Among the 240 5-year survivors, the 5-, 10-, and 15-year
      cumulative incidence of adverse outcomes included blindness: 10%, 13%, and 18%,
      respectively; hearing loss: 8%, 14%, and 22%; obesity/overweight: 18%, 35%, and
      53%; hyperinsulinism: 1%, 5%, and 24%; growth hormone deficiency: 13%, 27%, and
      29%;thyroid hormone deficiency: 16%, 28%, and 33%; and adrenocorticotropic
      hormone (ACTH) deficiency: 12%, 22%, and 26%. Multivariable models demonstrated
      radiation therapy to be a significant independent predictor of hearing loss,
      growth hormone deficiency, abnormal thyroid function, and ACTH deficiency.
      Diencephalic location was a statistically significant independent risk factor for
      blindness, growth hormone deficiency, abnormal thyroid function, and ACTH
      deficiency. Among the 182 5-year survivors assessed for intellectual function,
      34% had an intelligence quotient (IQ) below average (<85), associated with
      younger age at diagnosis, epilepsy, and shunt placement. Survivors of childhood
      LGG experience substantial long-term adverse effects that continue to increase
      well beyond the 5-year survival time point.

PMID- 21177782
TI  - miR-34a confers chemosensitivity through modulation of MAGE-A and p53 in
      medulloblastoma.
AB  - Recent studies have established miR-34a as a key effector of the p53 signaling
      pathway and have implicated its role in multiple cancer types. Here, we establish
      that miR-34a induces apoptosis, G2 arrest, and senescence in medulloblastoma and
      renders these cells more sensitive to chemotherapeutic agents. These effects are
      mediated in part by the direct post-transcriptional repression of the oncogenic
      MAGE-A gene family. We demonstrate that miR-34a directly targets the 3'
      untranslated regions of MAGE-A genes and decreases MAGE-A protein levels. This
      decrease in MAGE-A results in a concomitant increase in p53 and its associated
      transcriptional targets, p21/WAF1/CIP1 and, importantly, miR-34a. This
      establishes a positive feedback mechanism where miR-34a is not only induced by
      p53 but increases p53 mRNA and protein levels through the modulation of MAGE-A
      genes. Additionally, the forced expression of miR-34a or the knockdown of MAGE-A
      genes by small interfering RNA similarly sensitizes medulloblastoma cells to
      several classes of chemotherapeutic agents, including mitomycin C and cisplatin.
      Finally, the analysis of mRNA and micro-RNA transcriptional profiles of a series
      of primary medulloblastomas identifies a subset of tumors with low miR-34a
      expression and correspondingly high MAGE-A expression, suggesting the coordinate
      regulation of these genes. Our work establishes a role for miR-34a in modulating
      responsiveness to chemotherapy in medulloblastoma and presents a novel positive
      feedback mechanism involving miR-34a and p53, via direct targeting of MAGE-A.

PMID- 21177783
TI  - Pregabalin modulation of neurotransmitter release is mediated by change in
      intrinsic activation/inactivation properties of ca(v)2.1 calcium channels.
AB  - In this work, we studied the effects of the anticonvulsant and analgesic drug
      pregabalin (PGB) on excitatory postsynaptic currents (EPSCs) at principal neurons
      of the mouse medial nucleus of the trapezoid body and on presynaptic calcium
      currents at the calyx of Held. We found that the acute application of PGB reduced
      the amplitude of EPSCs in a dose-dependent manner with a maximal blocking effect
      of approximately 30%. A clinical high-concentration dose of PGB (e.g., 500 MUM)
      blocked Ca(v)2.1 channel-mediated currents and decreased their facilitation
      during a 100-Hz train, without changing their voltage-dependent activation.
      Furthermore, PGB also removed the inactivation of Ca(v)2.1 channels at a
      clinically relevant low concentration of 100 MUM. These results suggest novel
      modulatory mechanisms mediated by the acute administration of PGB on fast
      excitatory synaptic transmission and might contribute to better understanding PGB
      anticonvulsant/analgesic clinical effects.

PMID- 21177784
TI  - The association of growth hormone parameters with skeletal muscle phosphocreatine
      recovery in adult men.
AB  - CONTEXT: Previous studies have suggested a relationship between GH and
      mitochondrial function. However, little is known about the relationship of
      specific GH indices and in vivo measures of mitochondrial function in humans.
      OBJECTIVE: The objective of this study was to determine the association between
      GH, IGF-I, and phosphocreatine (PCr) recovery, a measure of mitochondrial
      function, in otherwise healthy adults. DESIGN: Thirty-seven healthy men and women
      were studied at a single university medical center. Subjects underwent GH
      stimulation testing with GH releasing hormone-arginine and measurement of IGF-I.
      Mitochondrial function was determined by PCr recovery after submaximal exercise
      by (31)Phosphorous magnetic resonance spectroscopy. Subjects underwent assessment
      of lean and fat mass with use of dual energy X-ray absorptiometry. RESULTS: There
      were no differences in PCr recovery between men and women (men 20.7+/-1.5 vs.
      women 24.8+/-1.4 mM/min; P > 0.05). IGF-I (r = 0.33; P = 0.04) was associated
      with PCr recovery in all subjects. Among men, IGF-I (r = 0.69; P = 0.003), peak
      stimulated GH (r = 0.52; P = 0.04), and GH area under the curve (AUC) (r = 0.53;
      P = 0.04) were significantly associated with PCr recovery. However, neither IGF
      I, peak stimulated GH, nor GH AUC (all P > 0.05) were associated with PCr
      recovery in women. After adjusting for age, race, and physical activity, IGF-I
      remained significantly associated with PCr recovery (beta = 0.10; P = 0.02) among
      men. CONCLUSIONS: IGF-I, peak stimulated GH, and GH AUC are associated with
      skeletal muscle PCr recovery in men.

PMID- 21177785
TI  - Vitamin D(3) is more potent than vitamin D(2) in humans.
AB  - BACKGROUND: Current unitage for the calciferols suggests that equimolar
      quantities of vitamins D(2) (D2) and D(3) (D3) are biologically equivalent.
      Published studies yield mixed results. OBJECTIVE: The aim of the study was to
      compare the potencies of D2 and D3. DESIGN: The trial used a single-blind,
      randomized design in 33 healthy adults. Calciferols were dosed at 50,000 IU/wk
      for 12 wk. Principal outcome variables were area under the curve for incremental
      total 25-hydroxyvitamin D [25(OH)D] and change in calciferol content of sc fat.
      RESULTS: Incremental mean (sd) 25(OH)D area under the curve at 12 wk was 1366 ng
      . d/ml (516) for the D2-treated group and 2136 (606) for the D3 (P < 0.001). Mean
      (sd) steady-state 25(OH)D increments showed similar differences: 24 ng/ml for D2
      (10.3) and 45 ng/ml (16.2) for D3 (P <0.001). Subcutaneous fat content of D2 rose
      by 50 MUg/kg in the D2-treated group, and D3 content rose by 104 MUg/kg in the D3
      treated group. Total calciferol in fat rose by only 33 ng/kg in the D2-treated,
      whereas it rose by 104 MUg/kg in the D3-treated group. Extrapolating to total
      body fat D3, storage amounted to just 17% of the administered dose. CONCLUSION:
      D3 is approximately 87% more potent in raising and maintaining serum 25(OH)D
      concentrations and produces 2- to 3-fold greater storage of vitamin D than does
      equimolar D2. For neither was there evidence of sequestration in fat, as had been
      postulated for doses in this range. Given its greater potency and lower cost, D3
      should be the preferred treatment option when correcting vitamin D deficiency.

PMID- 21177786
TI  - The effects of weight loss versus weight loss maintenance on sympathetic nervous
      system activity and metabolic syndrome components.
AB  - CONTEXT: Sympathetic nervous system (SNS) overactivity participates in both the
      pathogenesis and adverse clinical complications of metabolic syndrome (MetS)
      obesity. OBJECTIVE: We conducted a prospective lifestyle intervention trial to
      compare the effects of active weight loss and extended weight loss maintenance on
      SNS function and MetS components. METHODS: Untreated subjects (14 males, four
      females; mean age, 53 +/- 1 yr; body mass index, 30.9 +/- 0.9 kg/m(2)) who
      fulfilled Adult Treatment Panel III criteria were randomized to 12-wk hypocaloric
      diet alone (n = 8) or together with aerobic exercise training (n = 10). This was
      followed by a 4-month weight maintenance period. Measurements of muscle
      sympathetic nerve activity (MSNA) by microneurography, whole-body norepinephrine
      kinetics, substrate oxidation by indirect calorimetry, baroreflex sensitivity,
      plasma renin activity (PRA), and MetS components were performed. RESULTS: Body
      weight decreased by 9.3 +/- 0.8% at wk 12 (P < 0.001), and this was maintained.
      During active weight loss, norepinephrine spillover rate decreased by 23 +/- 16%
      (P = 0.004), MSNA by 25 +/- 3 bursts per 100 heartbeats (P < 0.001), and PRA by
      0.25 +/- 0.09 ng/ml . h (P = 0.007), whereas baroreflex sensitivity increased by
      5.2 +/- 2.2 msec/mm Hg (P = 0.005). After weight maintenance, beneficial effects
      of weight loss on norepinephrine spillover rate were preserved, whereas PRA and
      MSNA rebounded (by 0.24 +/- 0.11 ng/ml . h, P = 0.02; and 20 +/- 5 bursts/100
      heartbeats, P = 0.0003), and baroreflex sensitivity was attenuated. CONCLUSIONS:
      Divergent effects of successful weight loss maintenance on whole-body
      norepinephrine spillover rate and MSNA suggest organ-specific differentiation in
      SNS adaptation to weight loss under conditions of negative vs. stable energy
      balance.

PMID- 21177787
TI  - Sustained endoplasmic reticulum stress as a cofactor of oxidative stress in
      decidual cells from patients with early pregnancy loss.
AB  - BACKGROUND: Oxidative stress is a common pathological background for different
      etiologies of early pregnancy loss (EPL). It has been suggested that elevated
      reactive oxygen species trigger endoplasmic reticulum (ER) stress by influencing
      ER function. However, it is unclear whether ER stress is associated with EPL.
      OBJECTIVES: The aim of the study was to determine whether and how ER stress
      occurs during the development of EPL. APPROACHES: Proteomic analysis was
      performed on decidua from women with EPL, and then ER stress markers, redox
      status, apoptotic features, and cell viability were analyzed in EPL decidual
      cells (DCs). RESULTS: EPL decidua were characterized by decreased levels of
      glucose-regulated protein 78 (GPR78) and valosin-containing protein and burdened
      with ubiquitinated proteins. Evidence of ER stress-induced apoptosis in EPL DCs
      was demonstrated by extensive dilation of ER, morphological features of
      apoptosis, and activation of caspase-4 and caspase-12. Furthermore, H(2)O(2)
      reduced the viabilities in both EPL and control DCs, whereas EPL DCs were more
      vulnerable to additional OS challenge than the controls as a result of failed
      induction of GRP78 expression. The cell survival percentages of DCs were dose
      dependently reduced by H(2)O(2) and could be reversed in the presence of vitamin
      E. This effect was partly mediated by reducing the amount of misfolded proteins
      rather than regulating GRP78 expression. CONCLUSIONS: The sum of these
      observations demonstrate for the first time that sustained ER stress occurs in
      EPL DCs and the potentially vicious relationship between ER stress and oxidative
      stress is likely to play an important role in the development of EPL.

PMID- 21177788
TI  - Central and peripheral endocannabinoids and cognate acylethanolamides in humans:
      association with race, adiposity, and energy expenditure.
AB  - CONTEXT: Peripheral and central endocannabinoids and cognate acylethanolamides
      (AEs) may play important but distinct roles in regulating energy balance.
      OBJECTIVE: We hypothesized that in humans central/peripheral endocannabinoids are
      differently associated with adiposity and energy expenditure and differ by race.
      DESIGN: We examined associations of arachindonoylethanolamide, 2
      arachidonoylglycerol, palmitoylethanolamide, and oleoylethanolamide (OEA) assayed
      in plasma and cerebrospinal fluid (CSF) with race, adiposity, and energy
      expenditure. SETTING/PARTICIPANTS: In this monitored clinical inpatient study,
      CSF was obtained by lumbar puncture in 27 individuals (12 Caucasian, 11 American
      Indian, and four African-American). Twenty-four hour and sleep energy expenditure
      were measured by indirect calorimetry in a respiratory chamber. MAIN OUTCOME
      MEASURE: Samples were analyzed from a previous study originally designed to test
      a blood-brain barrier leptin transport deficit in human obesity. RESULTS: CSF
      (but not peripheral) 2-arachidonoylglycerol was significantly increased in
      American Indians compared with Caucasians (18.48 +/- 6.17 vs. 10.62 +/- 4.58
      pmol/ml, P < 0.01). In the whole group, peripheral AEs were positively but in CSF
      negatively associated with adiposity. However, in multivariate models adjusted
      for the other peripheral and CSF AEs, peripheral arachindonoylethanolamide was
      the only AE significantly associated with adiposity. Interestingly, CSF OEA
      concentrations were positively associated with adjusted 24 hour and sleep energy
      expenditure (r = 0.47, P < 0.05; r = 0.42, P < 0.05), but peripheral OEA was not.
      CONCLUSIONS: These data indicate a central alteration of the endocannabinoid
      system in American Indians and furthermore show that AEs in both compartments
      play an important but distinct role in human energy balance regulation.

PMID- 21177789
TI  - Pegylated long-acting human growth hormone possesses a promising once-weekly
      treatment profile, and multiple dosing is well tolerated in adult patients with
      growth hormone deficiency.
AB  - BACKGROUND: Recombinant human GH (rhGH) replacement therapy in children and
      adults currently requires daily sc injections for several years or lifelong,
      which may be both inconvenient and distressing for patients. NNC126-0083 is a
      pegylated rhGH developed for once-weekly administration. OBJECTIVES: Our
      objective was to evaluate the safety, tolerability, pharmacokinetics, and
      pharmacodynamics of multiple doses of NNC126-0083 in adult patients with GH
      deficiency (GHD). SUBJECTS AND METHODS: Thirty-three adult patients with GHD, age
      20-65 yr, body mass index 18.5-35.0 kg/m(2), and glycated hemoglobin of 8.0% or
      below. Fourteen days before randomization, subjects discontinued daily rhGH.
      NNC126-0083 (0.01, 0.02, 0.04, and 0.08 mg/kg) was given sc once weekly for 3 wk
      (NNC126-0083 for six subjects and placebo for two subjects). Blood samples were
      collected up to 168 h after the first and up to 240 h after the third dosing.
      Physical examination, antibodies, and local tolerability were assessed. RESULTS:
      NNC126-0083 was well tolerated with no difference in local tolerability compared
      with placebo and with no signs of lipoatrophy. A more than dose-proportional
      exposure was observed at the highest NNC126-0083 dose (0.16 mg protein/kg).
      Steady-state pharmacokinetics seemed achieved after the second dosing. A clear
      dose-dependent pharmacodynamic response in circulating IGF-I levels was observed
      [from a predose mean (SD) IGF-I SD score of -3.2 (1.7) to peak plasma
      concentration of -0.5 (1.3), 1.6 (1.3), 2.1 (0.5), and 4.4 (0.9) in the four dose
      groups, respectively]. CONCLUSION: After multiple dosing of NNC126-0083, a
      sustained pharmacodynamic response was observed. NNC126-0083 has the potential to
      serve as an efficacious, safe, and well-tolerated once-weekly treatment of adult
      patients with GHD.

PMID- 21177790
TI  - Bone marrow fat is inversely related to cortical bone in young and old subjects.
AB  - OBJECTIVE: Recent studies suggest a close local link between bone marrow
      adiposity and endosteal bone formation. Using magnetic resonance imaging, we
      examined whether the relation between the amount of marrow fat and cortical bone
      is present at multiple sites along the diaphyses of the long bones of young and
      old males and females. DESIGN: The relations between values for cortical bone
      area and percent marrow fat in each 5-mm section along the midthird of both
      femoral shafts were determined using magnetic resonance imaging in eight healthy
      young (aged <25 yr), and nine healthy old (aged >55 yr) men and women. RESULTS:
      Strong inverse correlations were observed between values for cortical bone area
      and percent marrow fat along the shafts of all 34 femurs; r values between -0.54
      to -0.97; all P values = 0.01-0.0001. The strength of this local association was
      comparable in the young and the elderly and in males and females. CONCLUSION: Our
      results underscore the strength of the local connections between bone and marrow
      adiposity. Increasing our understanding of the mechanism for this association
      could lead to better diagnosis and treatment approaches for osteoporosis.

PMID- 21177791
TI  - Dihydrotestosterone administration does not increase intraprostatic androgen
      concentrations or alter prostate androgen action in healthy men: a randomized
      controlled trial.
AB  - CONTEXT: Concern exists that androgen treatment might adversely impact prostate
      health in older men. Dihydrotestosterone (DHT), derived from local conversion of
      testosterone to DHT by 5alpha-reductase enzymes, is the principal androgen within
      the prostate. Exogenous androgens raise serum DHT concentrations, but their
      effects on the prostate are not clear. OBJECTIVE: To determine the impact of
      large increases in serum DHT concentrations on intraprostatic androgen
      concentrations and androgen action within the prostate. DESIGN: Double-blind,
      randomized, placebo-controlled. SETTING: Single academic medical center.
      PARTICIPANTS: 31 healthy men ages 35-55. INTERVENTION: Daily transdermal DHT or
      placebo gel. MAIN OUTCOME MEASURES: Serum and prostate tissue androgen
      concentrations and prostate epithelial cell gene expression after 4 wk of
      treatment. RESULTS: Twenty-seven men completed all study procedures. Serum DHT
      levels increased nearly sevenfold, while testosterone levels decreased in men
      treated with daily transdermal DHT gel but were unchanged in the placebo-treated
      group (P < 0.01 between groups). In contrast, intraprostatic DHT and testosterone
      concentrations on d 28 were not different between groups (DHT: placebo = 2.8 +/-
      0.2 vs. DHT gel = 3.1 +/- 0.5 ng/g; T: placebo = 0.6 +/- 0.2 vs. DHT gel = 0.4 +/
      0.1, mean +/- se). Similarly, prostate volume, prostate-specific antigen,
      epithelial cell proliferation, and androgen-regulated gene expression were not
      different between groups. CONCLUSIONS: Robust supraphysiologic increases in serum
      DHT, associated with decreased serum T, do not significantly alter intraprostatic
      levels of DHT, testosterone, or prostate epithelial cell androgen-regulated gene
      expression in healthy men. Changes in circulating androgen concentrations are not
      necessarily mimicked within the prostate microenvironment, a finding with
      implications for understanding the impact of androgen therapies in men.

PMID- 21177792
TI  - A highly sensitive, high-throughput assay for the detection of Turner syndrome.
AB  - OBJECTIVE: Turner syndrome (TS) occurs when an X-chromosome is completely or
      partially deleted or when X-chromosomal mosaicism is present. Girls with TS
      benefit from early diagnosis and treatment with GH; however, many girls with TS
      are not detected until after 10 yr of age, resulting in delayed evaluation and
      treatment. METHODS: We developed a high-throughput test for TS, based on a
      quantitative method of genotyping to detect X-chromosome abnormalities. This test
      uses pyrosequencing to quantitate relative allele strength (RAS) from single
      nucleotide polymorphisms using 18 informative single-nucleotide polymorphisms
      markers that span the X-chromosome and one marker for the detection of Y
      chromosome material. RESULTS: Cutoff ranges for heterozygous, homozygous, or out
      of-range RAS values were established from a cohort of 496 males and females.
      Positive TS scoring criteria were defined as the presence of homozygosity for all
      18 markers or the presence of at least one out-of-range RAS value. To determine
      the validity of this rapid test for TS detection, we undertook a large-scale
      study using DNA from 132 females without TS and 74 females with TS for whom
      karyotypes were available. TS was identified with 96.0% sensitivity and 97.0%
      specificity in this cohort. We also tested buccal swab DNA from a group of 19
      females without TS and 69 females with TS. In this group, TS was identified with
      97.1% sensitivity and 84.2% specificity. CONCLUSIONS: These results demonstrate
      the validity of a high-throughput, pyrosequencing based test for the accurate
      detection of TS, providing a potential alternative to karyotype testing.

PMID- 21177793
TI  - Comprehensive analysis of hormone and genetic variation in 36 genes related to
      steroid hormone metabolism in pre- and postmenopausal women from the breast and
      prostate cancer cohort consortium (BPC3).
AB  - CONTEXT: Sex steroids play a central role in breast cancer development.
      OBJECTIVE: This study aimed to relate polymorphic variants in 36 candidate genes
      in the sex steroid pathway to serum concentrations of sex steroid hormones and
      SHBG. DESIGN: Data on 700 genetic polymorphisms were combined with existing
      hormone assays and data on breast cancer incidence, within the European
      Prospective Investigation into Cancer and Nutrition (EPIC) and the Nurses' Health
      Study (NHS) cohorts; significant findings were reanalyzed in the Multiethnic
      Cohort (MEC). SETTING AND PARTICIPANTS: We analyzed data from a pooled sample of
      3852 pre- and postmenopausal Caucasian women from EPIC and NHS and 454
      postmenopausal women from MEC. MAIN OUTCOME MEASURES: Outcome measures were SHBG,
      testosterone, dehydroepiandrosterone (DHEAS), androstenedione, estrone (E1), and
      estradiol (E2) as well as breast cancer risk. RESULTS: Globally significant
      associations were found among pre- and postmenopausal women combined between
      levels of SHBG and the SHBG gene and between DHEAS and the FSHR and AKR1C3 genes.
      Among postmenopausal women, serum E1 and E2 were significantly associated with
      the genes CYP19 and FSHR, and E1 was associated with ESR1. None of the variants
      related to serum hormone levels showed any significant association with breast
      cancer risk. CONCLUSIONS: We confirmed associations between serum levels of SHBG
      and the SHBG gene and of E1 and E2 and the CYP19 and ESR1 genes. Novel
      associations were observed between FSHR and DHEAS, E1, and E2 and between AKR1C3
      and DHEAS.

PMID- 21177794
TI  - Activin-A and myostatin response and steroid regulation in human myometrium:
      disruption of their signalling in uterine fibroid.
AB  - CONTEXT: Investigation of activin-A (A) and myostatin (M) in human myometrium
      (HM) and leiomyoma (HL) will explain their involvement in human myometrial
      pathophysiology. OBJECTIVE: We aimed to investigate A and M response and steroid
      regulation in HM. We also evaluated A and M expression and response in HL.
      DESIGN: Tissues were analyzed and cultured. PATIENTS: Patients included fertile
      (in proliferative phase) and menopausal women undergoing hysterectomy.
      INTERVENTIONS: HM explant cultures were treated with A and M (for Smad-7 mRNA
      quantification) or estrogen and progesterone (for A and M mRNA quantification). A
      and M expression levels were also evaluated in menopausal (physiological absence
      of steroids) HM specimens. A and M and their receptors were evaluated in HL (n =
      8, diameter 5-8 cm) compared with their matched HM. HL explants cultures were
      treated with A and M (for Smad7 mRNA quantification), and, to explain the absence
      of response, the levels of follistatin, follistatin-related gene (FLRG), and
      Cripto were evaluated. RESULTS: A and M increased Smad7 expression in HM
      explants. A and M mRNAs were both reduced after estradiol treatment, unchanged
      after progesterone treatment, but were higher in menopausal than fertile (in
      proliferative phase) specimens. A, M, and FLRG were expressed at higher levels in
      HL compared with adjacent HM, whereas the receptors, follistatin, and Smad7 mRNAs
      resulted unchanged. Cripto mRNA was expressed only in HL. CONCLUSIONS: A and M
      act on human HM and are regulated by steroids. In HL there is an increase of A,
      M, FLRG, and Cripto expression.

PMID- 21177795
TI  - Hyperandrogenism in women with polycystic ovary syndrome persists after
      menopause.
AB  - CONTEXT: Ovarian and adrenal hyperandrogenism characterize premenopausal women
      with polycystic ovary syndrome (PCOS). Androgens decline with age in healthy and
      PCOS women. OBJECTIVE: The objective of the study was to investigate
      hyperandrogenism in PCOS after menopause. DESIGN: This was a case-control, cross
      sectional study. SETTING: The study was conducted at a university hospital
      endocrinology unit. PATIENTS: Twenty postmenopausal women with PCOS and 20 age-
      and body mass index-matched controls participated in the study. INTERVENTIONS:
      Serum cortisol, 17-hydroxyprogesterone (17-OHP), Delta(4)-androstenedione
      (Delta(4)A), dehydroepiandrosterone sulfate (DHEAS), total testosterone (T), and
      free androgen index (FAI) levels were measured at baseline, after ACTH
      stimulation, and after 3-d dexamethasone suppression. The ACTH and cortisol
      levels were measured during the CRH test. MAIN OUTCOME MEASURES: Androgen profile
      at baseline, after ACTH stimulation, and 3-d dexamethasone suppression tests were
      the main outcome measures. RESULTS: Postmenopausal PCOS women had higher 17-OHP,
      Delta(4)A, DHEAS, total T, FAI (P < 0.05) and lower SHBG (P < 0.05) baseline
      levels than control women. ACTH and cortisol responses during the CRH test were
      similar in the two groups. After ACTH stimulation, Delta(4)A, DHEAS, and total T
      levels were equally increased in both groups. After dexamethasone suppression, LH
      levels did not change in either group; 17-OHP-, Delta(4)A-, and FAI-suppressed
      levels remained higher in PCOS than in control women (P < 0.05), whereas total T
      and DHEAS levels were suppressed to similar values in both groups. CONCLUSIONS:
      In postmenopausal PCOS women, ACTH and cortisol responses to CRH are normal.
      Androgen levels at baseline are higher in PCOS than control women and remain
      increased after ACTH stimulation. The dexamethasone suppression results in
      postmenopausal PCOS women suggest that DHEAS and total T are partially of adrenal
      origin. Although the ovarian contribution was not fully assessed, increased
      Delta(4)A production suggests that the ovary also contributes to hyperandrogenism
      in postmenopausal PCOS women. In conclusion, postmenopausal PCOS women are
      exposed to higher adrenal and ovarian androgen levels than non-PCOS women.

PMID- 21177796
TI  - Adherence to a Mediterranean-type dietary pattern and cognitive decline in a
      community population.
AB  - BACKGROUND: Many of the foods abundant in the traditional Mediterranean diet,
      such as vegetables and fish, have been associated with slower cognitive decline.
      OBJECTIVE: We investigated whether adherence to a Mediterranean dietary pattern
      or to the Healthy Eating Index-2005 (HEI-2005) is associated with cognitive
      change in older adults. DESIGN: This article is based on analyses of data from an
      ongoing longitudinal study in adults aged >=65 y known as the Chicago Health and
      Aging Project (CHAP). CHAP participants (2280 blacks and 1510 whites) with >=2
      cognitive assessments were evaluated for adherence to 1) the Mediterranean
      dietary pattern (MedDiet; maximum score: 55) and 2) the HEI-2005 (maximum score:
      100). For both scoring systems, higher scores connote greater adherence.
      Cognitive function was assessed at 3-y intervals on the basis of a composite
      measure of global cognition. Linear mixed models were used to examine the
      association of dietary scores to change in cognitive function. Mean follow-up
      time was 7.6 y. RESULTS: Mean (+/-SD) scores for participants were 28.2 +/- 0.1
      for the MedDiet and 61.2 +/- 9.6 for the HEI-2005. White participants had higher
      energy-adjusted MedDiet scores but lower HEI-2005 scores than did black
      participants. Higher MedDiet scores were associated with slower rates of
      cognitive decline (beta = +0.0014 per 1-point increase, SEE = 0.0004, P = 0.0004)
      after adjustment for age, sex, race, education, participation in cognitive
      activities, and energy. No such associations were observed for HEI-2005 scores.
      CONCLUSION: The Mediterranean dietary pattern as captured by the MedDiet scoring
      system may reduce the rate of cognitive decline with older age.

PMID- 21177797
TI  - Clinical outcomes of a 2-y soy isoflavone supplementation in menopausal women.
AB  - BACKGROUND: Soy isoflavones are naturally occurring phytochemicals with weak
      estrogenic cellular effects. Despite numerous clinical trials of short-term
      isoflavone supplementation, there is a paucity of data regarding longer-term
      outcomes and safety. OBJECTIVE: Our aim was to evaluate the clinical outcomes of
      soy hypocotyl isoflavone supplementation in healthy menopausal women as a
      secondary outcome of a trial on bone health. DESIGN: A multicenter, randomized,
      double-blind, placebo-controlled 24-mo trial was conducted to assess the effects
      of daily supplementation with 80 or 120 mg aglycone equivalent soy hypocotyl
      isoflavones plus calcium and vitamin D on the health of 403 postmenopausal women.
      At baseline and after 1 and 2 y, clinical blood chemistry values were measured
      and a well-woman examination was conducted, which included a mammogram and a
      Papanicolaou test. A cohort also underwent transvaginal ultrasound measurements
      to assess endometrial thickness and fibroids. RESULTS: The baseline
      characteristics of the groups were similar. After 2 y of daily isoflavone
      exposure, all clinical chemistry values remained within the normal range. The
      only variable that changed significantly was blood urea nitrogen, which increased
      significantly after 2 y (P = 0.048) but not after 1 y (P = 0.343) in the
      supplementation groups. Isoflavone supplementation did not affect blood
      lymphocyte or serum free thyroxine concentrations. No significant differences in
      endometrial thickness or fibroids were observed between the groups. Two serious
      adverse events were detected (one case of breast cancer and one case of estrogen
      receptor-negative endometrial cancer), which was less than the expected
      population rate for these cancers. CONCLUSION: Daily supplementation for 2 y with
      80-120 mg soy hypocotyl isoflavones has minimal risk in healthy menopausal women.
      This trial was registered at clinicaltrials.gov as NCT00665860.

PMID- 21177798
TI  - Low-fat dietary pattern and change in body-composition traits in the Women's
      Health Initiative Dietary Modification Trial.
AB  - BACKGROUND: The Women's Health Initiative Dietary Modification (DM) Trial was a
      randomized controlled trial that compared the effects of a low-fat (<=20% of
      total energy) or a usual diet in relation to chronic disease risk in
      postmenopausal women. OBJECTIVE: We characterized long-term body-composition
      changes associated with the DM trial and potential modifiers of these
      associations. DESIGN: In the DM trial, 48,835 women aged 50-79 y were randomly
      assigned to intervention (40%) or comparison (60%) groups. We studied a subset
      with whole-body dual-energy X-ray absorptiometry scans at baseline and during
      follow-up. Changes in fat mass (FM), lean mass (LM), and percentage body fat
      between the intervention (n = 1580) and comparison (n = 2731) groups at years 1,
      3, and 6 were compared. By using generalized estimating equations, we calculated
      overall differences between groups and tested for interactions with age,
      diabetes, race-ethnicity (white, black, and Hispanic), body mass index (BMI), and
      hormone therapy (HT). RESULTS: The intervention women experienced significantly
      greater reductions in percentage body fat, FM, and LM at years 1 and 3 than did
      women in the comparison group (all P < 0.05). At year 6, only the FM change was
      significantly different between groups. Overall, the intervention was associated
      with reductions in percentage body fat (-0.8%; 95% CI: -1.0%, -0.6%), FM (-1.1
      kg; 95% CI: -1.3, -0.8 kg), and LM (-0.17 kg; 95% CI: -0.28, -0.06 kg) during
      follow-up (all P < 0.003). Intervention associations varied by race-ethnicity,
      BMI, diabetes, and HT and remained significant after adjustment for physical
      activity. CONCLUSION: This intervention was associated with modest long-term body
      composition changes; the findings were more robust in years 1 and 3. This trial
      was registered at clinicaltrials.gov as NCT00000611.

PMID- 21177799
TI  - Fruit, vegetables, and olive oil and risk of coronary heart disease in Italian
      women: the EPICOR Study.
AB  - BACKGROUND: Many observational studies support the recommendation to eat
      sufficient amounts of fruit and vegetables as part of a healthy diet. OBJECTIVE:
      The present study aimed to investigate the association between consumption of
      fruit, vegetables, and olive oil and the incidence of coronary heart disease
      (CHD) in 29,689 women enrolled between 1993 and 1998 in 5 European Prospective
      Investigation into Cancer and Nutrition (EPIC) cohorts in northern (Turin and
      Varese), central (Florence), and southern (Naples and Ragusa) Italy. DESIGN:
      Baseline dietary, anthropometric, and lifestyle characteristics were collected.
      Major events of CHD (fatal and nonfatal myocardial infarction and coronary
      revascularization) were identified through a review of clinical records. Analyses
      were stratified by center and adjusted for hypertension, smoking, education,
      menopause, physical activity, anthropometric measures, nonalcohol energy,
      alcohol, total meat, vegetables in analyses for fruit, and fruit in analyses for
      vegetables. RESULTS: During a mean follow-up of 7.85 y, 144 major CHD events were
      identified. A strong reduction in CHD risk among women in the highest quartile of
      consumption of leafy vegetables (hazard ratio: 0.54; 95% CI: 0.33, 0.90; P for
      trend = 0.03) and olive oil (hazard ratio: 0.56; 95% CI: 0.31, 0.99; P for trend
      = 0.04) was found. In contrast, no association emerged between fruit consumption
      and CHD risk. CONCLUSION: An inverse association between increasing consumption
      of leafy vegetables and olive oil and CHD risk emerged in this large cohort of
      Italian women.

PMID- 21177800
TI  - Inconsistencies in research reporting.

PMID- 21177801
TI  - Dietary intake patterns are reflected in metabolomic profiles: potential role in
      dietary assessment studies.
AB  - BACKGROUND: It has been suggested that metabolomics could play a role in dietary
      assessment and identification of novel biomarkers of dietary intake. OBJECTIVE:
      This study examined the link between habitual dietary patterns and metabolomic
      profiles. DESIGN: A total of 160 volunteers participated in a double-blind,
      randomized, placebo-controlled dietary intervention. We collected biofluids and
      recorded 3-d food diaries. Food data were reduced to 33 food groups, and a k
      means cluster analysis was performed to identify dietary patterns. (1)H Nuclear
      magnetic resonance (NMR) spectra were acquired for plasma and urine samples, and
      gas chromatography was used for plasma fatty acid profiling. RESULTS: Cluster
      analysis identified 3 distinct dietary patterns on the basis of the energy
      contribution of different food groups. Dietary clusters were reflected in plasma
      fatty acid profiles and in metabolomic data. (1)H NMR spectra of urine allowed
      the identification of metabolites associated with different dietary patterns.
      Several of the metabolites identified were linked to the intake of specific food
      groups; in particular, there was a positive association between O-acetylcarnitine
      and phenylacetylglutamine and red-meat and vegetable intakes, respectively.
      CONCLUSIONS: Habitual dietary patterns are shown in metabolomic data. This
      approach successfully identified potential biomarkers of red-meat and vegetable
      intakes.

PMID- 21177802
TI  - VEGFR2 and Src kinase inhibitors suppress Andes virus-induced endothelial cell
      permeability.
AB  - Hantaviruses predominantly infect human endothelial cells and, in the absence of
      cell lysis, cause two diseases resulting from increased vascular permeability.
      Andes virus (ANDV) causes a highly lethal acute pulmonary edema termed hantavirus
      pulmonary syndrome (HPS). ANDV infection enhances the permeability of endothelial
      cells in response to vascular endothelial growth factor (VEGF) by increasing
      signaling responses directed by the VEGFR2-Src-VE-cadherin pathway, which directs
      adherens junction (AJ) disassembly. Here we demonstrate that inhibiting pathway
      specific VEGFR2 and Src family kinases (SFKs) blocks ANDV-induced endothelial
      cell permeability. Small interfering RNA (siRNA) knockdown of Src within ANDV
      infected endothelial cells resulted in an ~70% decrease in endothelial cell
      permeability compared to that for siRNA controls. This finding suggested that
      existing FDA-approved small-molecule kinase inhibitors might similarly block ANDV
      induced permeability. The VEGFR2 kinase inhibitor pazopanib as well as SFK
      inhibitors dasatinib, PP1, bosutinib, and Src inhibitor 1 dramatically inhibited
      ANDV-induced endothelial cell permeability. Consistent with their kinase
      inhibitory concentrations, dasatinib, PP1, and pazopanib inhibited ANDV-induced
      permeability at 1, 10, and 100 nanomolar 50% inhibitory concentrations (IC(50)s),
      respectively. We further demonstrated that dasatinib and pazopanib blocked VE
      cadherin dissociation from the AJs of ANDV-infected endothelial cells by >90%.
      These findings indicate that VEGFR2 and Src kinases are potential targets for
      therapeutically reducing ANDV-induced endothelial cell permeability and, as a
      result, capillary permeability during HPS. Since the functions of VEGFR2 and SFK
      inhibitors are already well defined and FDA approved for clinical use, these
      findings rationalize their therapeutic evaluation for efficacy in reducing HPS
      disease. Endothelial cell barrier functions are disrupted by a number of viruses
      that cause hemorrhagic, edematous, or neurologic disease, and as a result, our
      findings suggest that VEGFR2 and SFK inhibitors should be considered for
      regulating endothelial cell barrier functions altered by additional viral
      pathogens.

PMID- 21177803
TI  - Acquisition of host-derived CD40L by HIV-1 in vivo and its functional
      consequences in the B-cell compartment.
AB  - Aberrant activation of the B-cell compartment and hypergammaglobulinemia were
      among the first recognized characteristics of HIV-1-infected patients in the
      early 1980s. It has been demonstrated previously that HIV-1 particles acquire the
      costimulatory molecule CD40L when budding from activated CD4(+) T cells. In this
      paper, we confirmed first that CD40L-bearing virions are detected in the plasma
      from untreated HIV-1-infected individuals. To define the biological functions of
      virus-associated CD40L and fully characterize its influence on the activation
      state of B cells, we conducted a large-scale gene expression analysis using
      microarray technology on B cells isolated from human tonsillar tissue.
      Comparative analyses of gene expression profiles revealed that CD40L-bearing
      virions induce a highly similar response to the one observed in samples treated
      with a CD40 agonist, indicating that virions bearing CD40L can efficiently
      activate B cells. Among modulated genes, many cytokines/chemokines (CCL17,
      CCL22), surface molecules (CD23, CD80, ICAM-1), members of the TNF superfamily
      (FAS, A20, TNIP1, CD40, lymphotoxin alpha, lymphotoxin beta), transcription
      factors and associated proteins (NFKB1, NFKBIA, NFKBIE), second messengers
      involved in CD40 signaling (TRAF1, TRAF3, MAP2K1, phosphatidylinositol 3-kinase),
      and the activation-induced cytidine deaminase (AID) were identified. Moreover, we
      show that soluble factors induced upon the exposure of B cells to CD40L-bearing
      virions can exert chemoattractant properties toward CD4(+) T cells. We thus
      propose that a positive feedback loop involving CD40L-bearing HIV-1 particles
      issued from CD4(+) T cells productively infected with HIV-1 play a role in the
      virus-induced dysfunction of humoral immunity by chronically activating B cells
      through sustained CD40 signaling.

PMID- 21177804
TI  - Intracellular assembly of cyanophage Syn5 proceeds through a scaffold-containing
      procapsid.
AB  - Syn5 is a marine cyanophage that is propagated on the marine photosynthetic
      cyanobacterial strain Synechococcus sp. WH8109 under laboratory conditions.
      Cryoelectron images of this double-stranded DNA (dsDNA) phage reveal an
      icosahedral capsid with short tail appendages and a single novel hornlike
      structure at the vertex opposite the tail. Despite the major impact of
      cyanophages on life in the oceans, there is limited information on cyanophage
      intracellular assembly processes within their photosynthetic hosts. The one-step
      growth curve of Syn5 demonstrated a short cycle with an eclipse period of ~45
      min, a latent phase of ~60 min, and a burst size of 20 to 30 particles per cell
      at 28 degrees C. SDS-PAGE and Western blot analysis of cell lysates at different
      times after infection showed the synthesis of major virion proteins and their
      increase as the infection progressed. The scaffolding protein of Syn5, absent
      from virions, was identified in the lysates and expressed from the cloned gene.
      It migrated anomalously on SDS-PAGE, similar to the phage T7 scaffolding protein.
      Particles lacking DNA but containing the coat and scaffolding proteins were
      purified from Syn5-infected cells using CsCl centrifugation followed by sucrose
      gradient centrifugation. Electron microscopic images of the purified particles
      showed shells lacking condensed DNA but filled with protein density, presumably
      scaffolding protein. These findings suggest that the cyanophages form infectious
      virions through the initial assembly of scaffolding-containing procapsids,
      similar to the assembly pathways for the enteric dsDNA bacteriophages. Since
      cyanobacteria predate the enteric bacteria, this procapsid-mediated assembly
      pathway may have originated with the cyanophages.

PMID- 21177805
TI  - Transcriptional profiling of CD4 T cells identifies distinct subgroups of HIV-1
      elite controllers.
AB  - Human immunodeficiency virus type 1 (HIV-1) elite controllers maintain
      undetectable levels of viral replication in the absence of antiretroviral therapy
      (ART), but their underlying immunological and virological characteristics may
      vary. Here, we used a whole-genome transcriptional profiling approach to
      characterize gene expression signatures of CD4 T cells from an unselected cohort
      of elite controllers. The transcriptional profiles for the majority of elite
      controllers were similar to those of ART-treated patients but different from
      those of HIV-1-negative persons. Yet, a smaller proportion of elite controllers
      showed an alternative gene expression pattern that was indistinguishable from
      that of HIV-1-negative persons but different from that of highly active
      antiretroviral therapy (HAART)-treated individuals. Elite controllers with the
      latter gene expression signature had significantly higher CD4 T cell counts and
      lower levels of HIV-1-specific CD8(+) T cell responses but did not significantly
      differ from other elite controllers in terms of HLA class I alleles, HIV-1 viral
      loads determined by ultrasensitive single-copy PCR assays, or chemokine receptor
      polymorphisms. Thus, these data identify a specific subgroup of elite controllers
      whose immunological and gene expression characteristics approximate those of HIV
      1-negative persons.

PMID- 21177806
TI  - The IFITM proteins inhibit HIV-1 infection.
AB  - Type I interferon protects cells from virus infection through the induction of a
      group of genes collectively named interferon-stimulated genes (ISGs). In this
      study, we utilized short hairpin RNA (shRNA) to deplete ISGs in SupT1 cells in
      order to identify ISGs that suppress the production of human immunodeficiency
      virus type 1 (HIV-1). Among the ISG candidates thus identified were interferon
      induced transmembrane (IFITM) proteins, including IFITM1, IFITM2, and IFITM3,
      that potently inhibit HIV-1 replication at least partially through interfering
      with virus entry. Further mutagenesis analysis shows that the intracellular
      region, rather than the N- and C-terminal extracellular domains, is essential for
      the antiviral activity of IFITM1. Altogether, these data suggest that the IFITM
      proteins serve as important components of the innate immune system to restrict
      HIV-1 infection.

PMID- 21177807
TI  - Foot-and-mouth disease virus exhibits an altered tropism in the presence of
      specific immunoglobulins, enabling productive infection and killing of dendritic
      cells.
AB  - Foot-and-mouth disease virus (FMDV) causes an acute vesicular disease of farm
      animals. The development of successful control strategies is limited by an
      incomplete understanding of the immune response to FMDV. Dendritic cells (DC)
      mediate the induction of immunity to pathogens, but their role in FMDV infection
      of cattle is uncharacterized. Bovine monocyte-derived DC (moDC) were exposed to
      integrin-binding and cell culture-adapted strains of FMDV in vitro. MoDC were not
      largely susceptible to infection by integrin-binding FMDV but were susceptible to
      culture-adapted virus. Binding specific antibodies to integrin-binding FMDV at
      neutralizing or subneutralizing IgG concentrations significantly enhanced
      infection via CD32 (FcgammaR). Monocytes also expressed CD32 but were
      nonsusceptible to FMDV immune complex (IC) infection, indicating a requirement
      for additional factors involved in cellular susceptibility. Infection of moDC by
      the FMDV IC was productive and associated with high levels of cell death.
      Infected moDC were unable to efficiently stimulate FMDV-specific CD4(+) memory T
      cells, but exposing moDC to IC containing inactivated FMDV resulted in
      significantly increased T cell stimulation. Thus, neutralized FMDV concurrently
      loses its ability to infect susceptible cells while gaining the capacity to
      infect immune cells. This represents a change in the tropism of FMDV that could
      occur after the onset of the antibody response. We propose that IC could
      dynamically influence the anti-FMDV immune response and that this may explain why
      the early immune response to FMDV has evolved toward T cell independence in vivo.
      Moreover, we propose that DC targeting could prove useful in the development of
      effective vaccines against FMDV.

PMID- 21177808
TI  - Orf virus ORFV121 encodes a novel inhibitor of NF-kappaB that contributes to
      virus virulence.
AB  - Orf virus (ORFV), the type member of the genus Parapoxvirus of the Poxviridae,
      has evolved novel strategies (proteins and/or mechanisms of action) to modulate
      host cell responses regulated by the nuclear factor-kappaB (NF-kappaB) signaling
      pathway. Here, we present data indicating that ORFV ORFV121, a gene unique to
      parapoxviruses, encodes a novel viral NF-kappaB inhibitor that binds to and
      inhibits the phosphorylation and nuclear translocation of NF-kappaB-p65. The
      infection of cells with an ORFV121 deletion mutant virus (OV-IA82Delta121)
      resulted in increased NF-kappaB-mediated gene transcription, and the expression
      of ORFV121 in cell cultures significantly suppressed NF-kappaB-regulated reporter
      gene expression. ORFV ORFV121 physically interacts with NF-kappaB-p65 in the cell
      cytoplasm, thus providing a mechanism for the inhibition of NF-kappaB-p65
      phosphorylation and nuclear translocation. Notably, the deletion of ORFV121 from
      the viral genome markedly decreased ORFV virulence and disease pathogenesis in
      sheep, indicating that ORFV121 is a virulence determinant for ORFV in the natural
      host.

PMID- 21177809
TI  - Diversity of interferon antagonist activities mediated by NSP1 proteins of
      different rotavirus strains.
AB  - Studies involving limited numbers of rotavirus (RV) strains have shown that the
      viral gene 5 product, NSP1, can antagonize beta interferon (IFN-beta) expression
      by inducing the degradation of IFN-regulatory factors (IRFs) (IRF3, IRF5, and
      IRF7) or a component of the E3 ubiquitin ligase complex responsible for
      activating NF-kappaB (beta-transducin repeat-containing protein [beta-TrCP]). To
      gain a broader perspective of NSP1 activities, we examined various RV strains for
      the ability to inhibit IFN-beta expression in human cells. We found that all
      strains encoding wild-type NSP1 impeded IFN-beta expression but not always
      through IRF3 degradation. To identify other degradation targets involved in
      suppressing IFN-beta expression, we used transient expression vectors to test the
      abilities of a diverse collection of NSP1 proteins to target IRF3, IRF5, IRF7,
      and beta-TrCP for degradation. The results indicated that human RVs rely
      predominantly on the NSP1-induced degradation of IRF5 and IRF7 to suppress IFN
      signaling, whereas NSP1 proteins of animal RVs tended to target IRF3, IRF5, and
      IRF7, allowing the animal viruses a broader attack on the IFN-beta signaling
      pathway. The results also suggested that the NSP1-induced degradation of beta
      TrCP is an uncommon mechanism of subverting IFN-beta signaling but is one that
      can be shared with NSP1 proteins that induce IRF degradation. Our analysis
      reveals that the activities of NSP1 proteins are diverse, with no obvious
      correlations between degradations of pairs of target proteins. Thus, RVs have
      evolved functionally distinct approaches for subverting the host antiviral
      response, a property consistent with the immense sequence variation noted for
      NSP1 proteins.

PMID- 21177810
TI  - Phosphatidylinositol 4-kinase III beta is a target of enviroxime-like compounds
      for antipoliovirus activity.
AB  - Enviroxime is an antienterovirus compound that targets viral protein 3A and/or
      3AB and suppresses a step in enterovirus replication by unknown mechanism. To
      date, four antienterovirus compounds, i.e., GW5074, Flt3 inhibitor II, TTP-8307,
      and AN-12-H5, are known to have similar mutations in the 3A protein-encoding
      region causing resistance to enviroxime (a G5318A [3A-Ala70Thr] mutation in
      poliovirus [PV]) and are considered enviroxime-like compounds. Recently,
      antienterovirus activity of a phosphatidylinositol 4-kinase III beta (PI4KB)
      inhibitor, PIK93, was reported, suggesting that PI4KB is an important host factor
      targetable by antienterovirus compounds (N. Y. Hsu et al., Cell 141:799-811,
      2010). In this study, we analyzed the inhibitory effects of previously identified
      enviroxime-like compounds (GW5074 and AN-12-H5) and a newly identified
      antienterovirus compound, T-00127-HEV1, on phosphoinositide (PI) kinases. We
      found that T-00127-HEV1 inhibited PI4KB activity with a higher specificity for
      than other PI kinases, in contrast to GW5074, which had a broad specificity for
      PI kinases. In contrast, AN-12-H5 showed no inhibitory effect on PI4KB activity
      and only moderate inhibitory effects on PI 3-kinase activity. Small interfering
      RNA (siRNA) screening targeting PI kinases identified PI4KB is a target of GW5074
      and T-00127-HEV1, but not of AN-12-H5, for anti-PV activity. Interestingly, T
      00127-HEV1 and GW5074 did not inhibit hepatitis C virus (HCV) replication, in
      contrast to a strong inhibitory effect of AN-12-H5. These results suggested that
      PI4KB is an enterovirus-specific host factor required for the replication process
      and targeted by some enviroxime-like compounds (T-00127-HEV1 and GW5074) and that
      enviroxime-like compounds may have targets other than PI kinases for their
      antiviral effect.

PMID- 21177811
TI  - Efficient culture adaptation of hepatitis C virus recombinants with genotype
      specific core-NS2 by using previously identified mutations.
AB  - Hepatitis C virus (HCV) is an important cause of chronic liver disease, and
      interferon-based therapy cures only 40 to 80% of patients, depending on HCV
      genotype. Research was accelerated by genotype 2a (strain JFH1) infectious cell
      culture systems. We previously developed viable JFH1-based recombinants encoding
      the structural proteins (core, E1, E2), p7, and NS2 of prototype isolates of the
      seven major HCV genotypes; most recombinants required adaptive mutations. To
      enable genotype-, subtype-, and isolate-specific studies, we developed efficient
      core-NS2 recombinants from additional genotype 1a (HC-TN and DH6), 1b (DH1 and
      DH5), and 3a (DBN) isolates, using previously identified adaptive mutations.
      Introduction of mutations from isolates of the same subtype either led to
      immediate efficient virus production or accelerated culture adaptation. The DH6
      and DH5 recombinants without introduced mutations did not adapt to culture.
      Universal adaptive effects of mutations in NS3 (Q1247L, I1312V, K1398Q, R1408W,
      and Q1496L) and NS5A (V2418L) were investigated for JFH1-based genotype 1 to 5
      core-NS2 recombinants; several mutations conferred adaptation to H77C (1a), J4
      (1b), S52 (3a), and SA13 (5a) but not to ED43 (4a). The mutations permitting
      robust virus production in Huh7.5 cells had no apparent effect on viral
      replication but allowed efficient assembly of intracellular infectious HCV for
      adapted novel or previously developed recombinants. In conclusion, previously
      identified mutations permitted development of novel HCV core-NS2 genotype
      recombinants. Mutations adapting several recombinants to culture were identified,
      but no mutations were universally adaptive across genotypes. This work provides
      tools for analysis of HCV genotype specificity and may promote the understanding
      of genotype-specific patterns in HCV disease and control.

PMID- 21177812
TI  - A single mutation responsible for temperature-sensitive entry and assembly
      defects in the VP1-2 protein of herpes simplex virus.
AB  - Evidence for an essential role of the herpes simplex virus type 1 (HSV-1)
      tegument protein VP1-2 originated from the analysis of the temperature-sensitive
      (ts) mutant tsB7. At the nonpermissive temperature (NPT), tsB7 capsids accumulate
      at the nuclear pore, with defective genome release and substantially reduced
      virus gene expression. We compared the UL36 gene of tsB7 with that of the
      parental strain HFEM or strain 17 and identified four amino acid substitutions,
      1061D -> G, 1453Y -> H, 2273Y -> H, and 2558T -> I. We transferred the UL36 gene
      from tsB7, HFEM, or strain 17 into a KOS background. While KOS recombinants
      containing the HFEM or strain 17 UL36 gene exhibited no ts defect, recombinants
      containing the tsB7 UL36 VP1-2 exhibited a 5-log deficiency at the NPT.
      Incubation at the NPT resulted in little or no virus gene expression, though
      limited expression could be detected in a highly delayed fashion. Using shift
      down regimes, gene expression recovered and recapitulated the time course
      normally observed, indicating that the initial block was in a reversible pathway.
      Using temperature shift-up regimes, a second defect later in the replication
      cycle was also observed in the KOS.ts viruses. We constructed a further series of
      recombinants which contained subsets of the four substitutions. A virus
      containing the wild-type (wt) residue at position 1453 and with the other three
      residues being from tsB7 VP1-2 exhibited wt plaquing efficiency. Conversely, a
      virus containing the three wt residues but the single Y -> H change at position
      1453 from tsB7 exhibited a 4- to 5-log drop in plaquing efficiency and was
      defective at both early and late stages of infection.

PMID- 21177813
TI  - Structural flexibility allows the functional diversity of potyvirus genome-linked
      protein VPg.
AB  - Several viral genome-linked proteins (VPgs) of plant viruses are intrinsically
      disordered and undergo folding transitions in the presence of partners. This
      property has been postulated to be one of the factors that enable the functional
      diversity of the protein. We created a homology model of Potato virus A VPg and
      positioned the known functions and structural properties of potyviral VPgs on the
      novel structural model. The model suggests an elongated structure with a
      hydrophobic core composed of antiparallel beta-sheets surrounded by helices and a
      positively charged contact surface where most of the known activities are
      localized. The model most probably represents the fold induced immediately after
      binding of VPg to a negatively charged lipid surface or to SDS. When the charge
      of the positive surface was lowered by lysine mutations, the efficiencies of in
      vitro NTP binding, uridylylation reaction, and unspecific RNA binding were
      reduced and in vivo the infectivity was debilitated. The most likely
      uridylylation site, Tyr63, locates to the positively charged surface.
      Surprisingly, a Tyr63Ala mutation did not prevent replication completely but
      blocked spreading of the virus. Based on the localization of Tyr119 in the model,
      it was hypothesized to serve as an alternative uridylylation site. Evidence to
      support the role of Tyr119 in replication was obtained which gives a positive
      example of the prediction power of the model. Taken together, our experimental
      data support the features presented in the model and the idea that the functional
      diversity is attributable to structural flexibility.

PMID- 21177814
TI  - Varicella-zoster virus transcriptome in latently infected human ganglia.
AB  - We recently developed a novel multiplex reverse transcription (RT)-PCR assay that
      allows rapid and sensitive detection of transcripts corresponding to all 68
      unique varicella-zoster virus (VZV) open reading frames (ORFs) in only five
      amplification reactions (M. A. Nagel, D. Gilden, T. Shade, B. Gao, and R. J.
      Cohrs, J. Virol. Methods 157:62-68, 2009). Herein, we applied multiplex RT-PCR
      analysis to mRNA extracted from 26 trigeminal ganglia latently infected with VZV
      and one control trigeminal ganglion negative for VZV DNA that were removed from
      14 men and women, 16 to 84 years of age, within 24 h after death. Analysis
      identified VZV transcripts mapping to VZV ORFs 29, 62, and 63, previously
      detected and sequence verified; VZV ORFs 4 and 40, previously detected by in situ
      hybridization; and VZV ORFs 11, 41, 43, 57, and 68, not previously detected. VZV
      ORF 63 transcripts were the most prevalent. Comparison of the 10 VZV ORFs
      transcribed during latency to their herpes simplex virus type 1 homologues
      reveals that the latently transcribed VZV genes encode immediate-early, early,
      and late transcripts.

PMID- 21177815
TI  - EBNA3C attenuates the function of p53 through interaction with inhibitor of
      growth family proteins 4 and 5.
AB  - Epstein-Barr virus (EBV)-encoded EBNA3C is one of the latent proteins essential
      for the efficient transformation of human primary B lymphocytes into continuously
      proliferating lymphoblastoid cell lines (LCLs) in vitro through manipulation of a
      number of major cellular pathways. Although it does not have direct DNA-binding
      activity, EBNA3C plays a central role in the transcriptional modulation of a wide
      range of both viral and cellular genes during latent infection. Recently, we
      showed that EBNA3C can directly bind to the tumor suppressor protein p53 and
      repress its functions, in part by blocking its transcriptional activity as well
      as facilitating its degradation through stabilization of its negative regulator,
      Mdm2. In this study, we further showed that EBNA3C can negatively regulate p53
      mediated functions by interacting with its regulatory proteins, the inhibitor of
      growth family proteins ING4 and ING5, shown to be frequently deregulated in
      different cancers. Functional mapping revealed that both ING4 and ING5 bound to N
      terminal domain residues 129 to 200 of EBNA3C, which was previously demonstrated
      to associate with p53 and is also essential for LCL growth. In addition, we
      showed that a conserved domain of either ING4 or ING5 bound to both p53 and
      EBNA3C in a competitive manner, suggesting a potential role for EBNA3C whereby
      the ING4 or -5/p53 pathway is modulated in EBV-infected cells. Subsequently, we
      demonstrated that EBNA3C significantly suppresses both the ING4- and ING5
      mediated regulation of p53 transcriptional activity in a dose-dependent manner. A
      colony formation assay as well as an apoptosis assay showed that EBNA3C nullified
      the negative regulatory effects on cell proliferation induced by coupled
      expression of p53 in the presence of either ING4 or ING5 in Saos-2 (p53(-/-))
      cells. This report demonstrates a possible role for the candidate tumor
      suppressor ING genes in the biology of EBV-associated cancers.

PMID- 21177816
TI  - A single amino acid substitution in the capsid of foot-and-mouth disease virus
      can increase acid resistance.
AB  - Foot-and-mouth disease virus (FMDV) particles lose infectivity due to their
      disassembly at pH values slightly below neutrality. This acid-dependent
      disassembly process is required for viral RNA release inside endosomes. To study
      the molecular determinants of viral resistance to acid-induced disassembly, six
      FMDV variants with increased resistance to acid inactivation were isolated.
      Infection by these mutants was more sensitive to drugs that raise the endosomal
      pH (NH(4)Cl and concanamycin A) than was infection by the parental C-S8c1 virus,
      confirming that the increase in acid resistance is related to a lower pH
      requirement for productive uncoating. Amino acid replacement N17D at the N
      terminus of VP1 capsid protein was found in all six mutants. This single
      substitution was shown to be responsible for increased acid resistance when
      introduced into an infectious FMDV clone. The increased resistance of this mutant
      against acid-induced inactivation was shown to be due to its increased resistance
      against capsid dissociation into pentameric subunits. Interestingly, the N17D
      mutation was located close to but not at the interpentamer interfaces. The
      mutants described here extend the panel of FMDV variants exhibiting different pH
      sensitivities and illustrate the adaptive flexibility of viral quasispecies to pH
      variations.

PMID- 21177817
TI  - Access to RNA encapsidated in the nucleocapsid of vesicular stomatitis virus.
AB  - The genomic RNA of negative-strand RNA viruses, such as vesicular stomatitis
      virus (VSV), is completely enwrapped by the nucleocapsid protein (N) in every
      stage of virus infection. During viral transcription/replication, however, the
      genomic RNA in the nucleocapsid must be accessible by the virus-encoded RNA
      dependent RNA polymerase in order to serve as the template for RNA synthesis.
      With the VSV nucleocapsid and a nucleocapsid-like particle (NLP) produced in
      Escherichia coli, we have found that the RNA in the VSV nucleocapsid can be
      removed by RNase A, in contrast to what was previously reported. Removal of the
      RNA did not disrupt the assembly of the N protein, resulting in an empty capsid.
      Polyribonucleotides were reencapsidated into the empty NLP, and the crystal
      structures were determined. The crystal structures revealed variable degrees of
      association of the N protein with a specific RNA sequence.

PMID- 21177818
TI  - Tupaia CD81, SR-BI, claudin-1, and occludin support hepatitis C virus infection.
AB  - Hepatitis C virus (HCV)-related research has been hampered by the lack of
      appropriate small-animal models. It has been reported that tree shrews, or
      tupaias (Tupaia belangeri), can be infected with serum-derived HCV. However,
      these reports do not firmly establish the tupaia as a reliable model of HCV
      infection. Human CD81, scavenger receptor class B type I (SR-BI), claudin 1
      (CLDN1), and occludin (OCLN) are considered essential receptors or coreceptors
      for HCV cell entry. In the present study, the roles of these tupaia orthologs in
      HCV infection were assessed. Both CD81 and SR-BI of tupaia were found to be able
      to bind with HCV envelope protein 2 (E2). In comparison with human CD81, tupaia
      CD81 exhibited stronger binding activity with E2 and increased HCV pseudoparticle
      (HCVpp) cell entry 2-fold. The 293T cells transfected with tupaia CLDN1 became
      susceptible to HCVpp infection. Moreover, simultaneous transfection of the four
      tupaia factors into mouse NIH 3T3 cells made the cells susceptible to HCVpp
      infection. HCVpp of diverse genotypes were able to infect primary tupaia
      hepatocytes (PTHs), and this infection could be blocked by either anti-CD81 or
      anti-SR-BI. PTHs could be infected by cell culture-produced HCV (HCVcc) and did
      produce infectious progeny virus in culture supernatant. These findings indicate
      that PTHs possess all of the essential factors required for HCV entry and support
      the complete HCV infection cycle. This highlights both the mechanisms of
      susceptibility of tupaia to HCV infection and the possibility of using tupaia as
      a promising small-animal model in HCV study.

PMID- 21177819
TI  - Establishment of a chimeric, replication-deficient influenza A virus vector by
      modulation of splicing efficiency.
AB  - Segment 8 of the influenza A virus codes for two proteins (NS1 and NS2/NEP) via
      splicing. Here, we developed a viral vector expressing a cytokine or chemokine
      instead of the interferon antagonist NS1. To achieve both the desired genetic
      stability and high transgene expression levels, NS2/NEP mRNA splicing efficacy
      had to be fine-tuned by modification of splicing elements. Expression levels of
      secreted foreign proteins could be further enhanced by fusing the N-terminal 13
      amino acids of NS1 with an IgK-derived secretion signal peptide. Thus, the first
      start codon was used for translation initiation of both NS2/NEP and the foreign
      protein.

PMID- 21177820
TI  - Complementing defective viruses that express separate paramyxovirus glycoproteins
      provide a new vaccine vector approach.
AB  - Replication-defective vaccine vectors based on vesicular stomatitis virus (VSV)
      lacking its envelope glycoprotein gene (G) are highly effective in animal models.
      However, such DeltaG vectors are difficult to grow because they require
      complementation with the VSV G protein. In addition, the complementing G protein
      induces neutralizing antibodies in animals and thus limits multiple vector
      applications. In the process of generating an experimental Nipah virus (a
      paramyxovirus) vaccine, we generated two defective VSVDeltaG vectors, each
      expressing one of the two Nipah virus (NiV) glycoproteins (G and F) that are both
      required for virus entry to host cells. These replication-defective VSV vectors
      were effective at generating NiV neutralizing antibody in mice. Most
      interestingly, we found that these two defective viruses could be grown together
      and passaged in tissue culture cells in the absence of VSV G complementation.
      This mixture of complementing defective viruses was also highly effective at
      generating NiV neutralizing antibody in animals. This novel approach to growing
      and producing a vaccine from two defective viruses could be generally applicable
      to vaccine production for other paramyxoviruses or for other viruses where the
      expression of at least two different proteins is required for viral entry. Such
      an approach minimizes biosafety concerns that could apply to single, replication
      competent VSV recombinants expressing all proteins required for infection.

PMID- 21177821
TI  - The PA protein directly contributes to the virulence of H5N1 avian influenza
      viruses in domestic ducks.
AB  - During their circulation in nature, H5N1 avian influenza viruses (AIVs) have
      acquired the ability to kill their natural hosts, wild birds and ducks. The
      genetic determinants for this increased virulence are largely unknown. In this
      study, we compared two genetically similar H5N1 AIVs, A/duck/Hubei/49/05 (DK/49)
      and A/goose/Hubei/65/05 (GS/65), that are lethal for chickens but differ in their
      virulence levels in ducks. To explore the genetic basis for this difference in
      virulence, we generated a series of reassortants and mutants of these two
      viruses. The virulence of the reassortant bearing the PA gene from DK/49 in the
      GS/65 background increased 10(5)-fold relative to that of the GS/65 virus.
      Substitution of two amino acids, S224P and N383D, in PA contributed to the highly
      virulent phenotype. The amino acid 224P in PA increased the replication of the
      virus in duck embryo fibroblasts, and the amino acid 383D in PA increased the
      polymerase activity in duck embryo fibroblasts and delayed the accumulation of
      the PA and PB1 polymerase subunits in the nucleus of virus-infected cells. Our
      results provide strong evidence that the polymerase PA subunit is a virulence
      factor for H5N1 AIVs in ducks.

PMID- 21177822
TI  - The herpes simplex virus type 1 latency-associated transcript can protect neuron
      derived C1300 and Neuro2A cells from granzyme B-induced apoptosis and CD8 T-cell
      killing.
AB  - The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) is
      the only HSV-1 gene transcript abundantly expressed throughout latency. LAT null
      mutants have a significantly reduced reactivation phenotype. LAT's antiapoptosis
      activity is the major LAT factor involved in supporting the wild-type
      reactivation phenotype. During HSV-1 latency, some ganglionic neurons are
      surrounded by CD8 T cells, and it has been proposed that these CD8 T cells help
      maintain HSV-1 latency by suppressing viral reactivations. Surprisingly, despite
      injection of cytotoxic lytic granules by these CD8 T cells into latently infected
      neurons, neither apoptosis nor neuronal cell death appears to occur. We
      hypothesized that protection of latently infected neurons against cytotoxic CD8 T
      cell killing is due to LAT's antiapoptosis activity. Since CD8 T-cell cytotoxic
      lytic granule-mediated apoptosis is critically dependent on granzyme B (GrB), we
      examined LAT's ability to block GrB-induced apoptosis. We report here that (i)
      LAT can interfere with GrB-induced apoptosis in cell cultures, (ii) LAT can block
      GrB-induced cleavage (activation) of caspase-3 both in cell culture and in a cell
      free in vitro cell extract assay, and (iii) LAT can protect C1300 and Neuro2A
      cells from cytotoxic CD8 T-cell killing in vitro. These findings support the
      hypothesis that LAT's antiapoptosis activity can protect latently infected
      neurons from being killed by CD8 T-cell lytic granules in vivo.

PMID- 21177824
TI  - Human Ago2 is required for efficient microRNA 122 regulation of hepatitis C virus
      RNA accumulation and translation.
AB  - MicroRNA 122 (miR-122) increases the accumulation and translation of hepatitis C
      virus (HCV) RNA in infected cells through direct interactions with homologous
      sequences in the 5' untranslated region (UTR) of the HCV genome. Argonaute 2
      (Ago2) is a component of the RNA-induced silencing complex (RISC) and mediates
      small interfering RNA (siRNA)-directed mRNA cleavage and microRNA translational
      suppression. We investigated the function of Ago2 in HCV replication to determine
      whether it plays a role in enhancing the synthesis and translation of HCV RNA
      that is associated with miR-122. siRNA-mediated depletion of Ago2 in human
      hepatoma cells reduced HCV RNA accumulation in transient HCV replication assays.
      The treatment did not adversely affect cell viability, as assessed by cell
      proliferation, capped translation, and interferon assays. These data are
      consistent with complementary roles for Ago2 and miR-122 in enhancing HCV RNA
      amplification. By using a transient HCV replication assay that is dependent on an
      exogenously provided mutant miR-122, we determined that Ago2 depletion still
      reduced luciferase expression and HCV RNA accumulation, independently of miR-122
      biogenesis. miR-122 has previously been found to stimulate HCV translation.
      Similarly, Ago2 knockdown also reduced HCV translation, and its depletion reduced
      the ability of miR-122 to stimulate viral translation. These data suggest a
      direct role for Ago2 in miR-122-mediated translation. Finally, Ago2 was also
      necessary for efficient miR-122 enhancement of HCV RNA accumulation. These data
      support a model in which miR-122 functions within an Ago2-containing protein
      complex to augment both HCV RNA accumulation and translation.

PMID- 21177823
TI  - The human cytomegalovirus protein UL37 exon 1 associates with internal lipid
      rafts.
AB  - The human cytomegalovirus (HCMV) protein UL37 exon 1 (pUL37x1), also known as
      viral mitochondrion-localized inhibitor of apoptosis (vMIA), sequentially
      traffics from the endoplasmic reticulum (ER) through mitochondrion-associated
      membranes (MAMs) to the outer mitochondrial membrane (OMM), where it robustly
      inhibits apoptosis. Here, we report the association of pUL37x1/vMIA with internal
      lipid rafts (LRs) in the ER/MAM. The MAM, which serves as a site for lipid
      transfer and calcium signaling to mitochondria, is enriched in detergent
      resistant membrane (DRM)-forming lipids, including cholesterol and ceramide,
      which are found in lower concentrations in the bulk ER. Sigma 1 receptor (Sig
      1R), a MAM chaperone affecting calcium signaling to mitochondria, is anchored in
      the MAM by its LR association. Because of its trafficking through the MAM and
      partial colocalization with Sig-1R, we tested whether pUL37x1/vMIA associates
      with MAM LRs. Extraction with methyl-beta-cyclodextrin (MbetaCD) removed
      pUL37x1/vMIA from lysed but not intact cells, indicating its association with
      internal LRs. Furthermore, the isolation of DRMs from purified intracellular
      organelles independently verified the localization of pUL37x1/vMIA within ER/MAM
      LRs. However, pUL37x1/vMIA was not detected in DRMs from mitochondria.
      pUL37x1/vMIA associated with LRs during all temporal phases of HCMV infection,
      indicating the likely importance of this location for HCMV growth. Although
      detected during its sequential trafficking to the OMM, the pUL37x1/vMIA LR
      association was independent of its mitochondrial targeting signals. Rather, it
      was dependent upon cholesterol binding. These studies suggest a conserved ability
      of UL37 proteins to interact with cholesterol and LRs, which is functionally
      distinguishable from their sequential trafficking to mitochondria.

PMID- 21177825
TI  - Hepatitis B virus surface antigen assembly function persists when entire
      transmembrane domains 1 and 3 are replaced by a heterologous transmembrane
      sequence.
AB  - Native hepatitis B surface antigen (HBsAg) spontaneously assembles into 22-nm
      subviral particles. The particles are lipoprotein micelles, in which HBsAg is
      believed to span the lipid layer four times. The first two transmembrane domains,
      TM1 and TM2, are required for particle assembly. We have probed the requirements
      for particle assembly by replacing the entire first or third TM domain of HBsAg
      with the transmembrane domain of HIV gp41. We found that either TM domain of
      HBsAg could be replaced, resulting in HBsAg-gp41 chimeras that formed particles
      efficiently. HBsAg formed particles even when both TM1 and TM3 were replaced with
      the gp41 domain. The results indicate remarkable flexibility in HBsAg particle
      formation and provide a novel way to express heterologous membrane proteins that
      are anchored to a lipid surface by their own membrane-spanning domain. The
      membrane-proximal exposed region (MPER) of gp41 is an important target of broadly
      reactive neutralizing antibodies against HIV-1, and HBsAg-MPER particles may
      provide a good platform for future vaccine development.

PMID- 21177826
TI  - In vivo kinetics of U4/U6.U5 tri-snRNP formation in Cajal bodies.
AB  - The U4/U6.U5 tri-small nuclear ribonucleoprotein particle (tri-snRNP) is an
      essential pre-mRNA splicing factor, which is assembled in a stepwise manner
      before each round of splicing. It was previously shown that the tri-snRNP is
      formed in Cajal bodies (CBs), but little is known about the dynamics of this
      process. Here we created a mathematical model of tri-snRNP assembly in CBs and
      used it to fit kinetics of individual snRNPs monitored by fluorescence recovery
      after photobleaching. A global fitting of all kinetic data determined key
      reaction constants of tri-snRNP assembly. Our model predicts that the rates of di
      snRNP and tri-snRNP assemblies are similar and that ~230 tri-snRNPs are assembled
      in one CB per minute. Our analysis further indicates that tri-snRNP assembly is
      approximately 10-fold faster in CBs than in the surrounding nucleoplasm, which is
      fully consistent with the importance of CBs for snRNP formation in rapidly
      developing biological systems. Finally, the model predicted binding between SART3
      and a CB component. We tested this prediction by Forster resonance energy
      transfer and revealed an interaction between SART3 and coilin in CBs.

PMID- 21177827
TI  - A novel acetylation of beta-tubulin by San modulates microtubule polymerization
      via down-regulating tubulin incorporation.
AB  - Dynamic instability is a critical property of microtubules (MTs). By regulating
      the rate of tubulin polymerization and depolymerization, cells organize the MT
      cytoskeleton to accommodate their specific functions. Among many processes,
      posttranslational modifications of tubulin are implicated in regulating MT
      functions. Here we report a novel tubulin acetylation catalyzed by
      acetyltransferase San at lysine 252 (K252) of beta-tubulin. This acetylation,
      which is also detected in vivo, is added to soluble tubulin heterodimers but not
      tubulins in MTs. The acetylation-mimicking K252A/Q mutants were incorporated into
      the MT cytoskeleton in HeLa cells without causing any obvious MT defect. However,
      after cold-induced catastrophe, MT regrowth is accelerated in San-siRNA cells
      while the incorporation of acetylation-mimicking mutant tubulins is severely
      impeded. K252 of beta-tubulin localizes at the interface of alpha-/beta-tubulins
      and interacts with the phosphate group of the alpha-tubulin-bound GTP. We propose
      that the acetylation slows down tubulin incorporation into MTs by neutralizing
      the positive charge on K252 and allowing tubulin heterodimers to adopt a
      conformation that disfavors tubulin incorporation.

PMID- 21177828
TI  - Differential effects of PPAR-{gamma} activation versus chemical or genetic
      reduction of DPP-4 activity on bone quality in mice.
AB  - Patients with type 2 diabetes mellitus have an increased risk of fracture that
      can be further exacerbated by thiazolidinediones. A new class of antidiabetic
      agents control glucose through reduction of dipeptidyl peptidase-4 (DPP-4)
      activity; however the importance of DPP-4 for the control of bone quality has not
      been extensively characterized. We compared the effects of the thiazolidinedione
      pioglitazone and the DPP-4 inhibitor sitagliptin on bone quality in high-fat diet
      (HFD)-fed wild-type mice. In complementary studies, we examined bone quality in
      Dpp4(+/+) vs. Dpp4(-/-) mice. Pioglitazone produced yellow bones with greater
      bone marrow adiposity and significantly reduced vertebral bone mechanics in male,
      female, and ovariectomized (OVX) HFD fed female mice. Pioglitazone negatively
      affected vertebral volumetric bone mineral density, trabecular architecture, and
      mineral apposition rate in male mice. Sitagliptin treatment of HFD-fed wild-type
      mice significantly improved vertebral volumetric bone mineral density and
      trabecular architecture in female mice, but these improvements were lost in
      females after OVX. Genetic inactivation of Dpp4 did not produce a major bone
      phenotype in male and female Dpp4(-/-) mice; however, OVX Dpp4(-/-) mice
      exhibited significantly reduced femoral size and mechanics. These findings
      delineate the skeletal consequences of pharmacological and genetic reduction of
      DPP-4 activity and reveal significant differences in the effects of pioglitazone
      vs. sitagliptin vs. genetic Dpp4 inactivation on bone mechanics in mice.

PMID- 21177829
TI  - Bioluminescence resonance energy transfer reveals the adrenocorticotropin (ACTH)
      induced conformational change of the activated ACTH receptor complex in living
      cells.
AB  - The melanocortin 2 receptor (MC2R) accessory protein (MRAP) is a small single
      transmembrane domain protein that plays a pivotal role in the function of the
      MC2R. The pituitary hormone, ACTH, acts via this receptor complex to stimulate
      adrenal steroidogenesis. Using both coimmunoprecipitation and bioluminescence
      resonance energy transfer (BRET), we show that the MC2R is constitutively
      homodimerized in cells. Furthermore, consistent with previous data, we also show
      that MRAP exists as an antiparallel homodimer. ACTH enhanced the BRET signal
      between MC2R homodimers as well as MC2R-MRAP heterodimers. However, ACTH did not
      enhance the physical interaction between these dimers as determined by
      coimmunoprecipitation. Real-time BRET analysis of the MRAP-MC2R interaction
      revealed two distinct phases of the ACTH-dependent BRET increase, an initial
      complex series of changes occurring over the first 2 min and a later persistent
      increase in BRET signal. The slower ACTH-dependent phase was inhibited by the
      protein kinase A inhibitor KT5720, suggesting that signal transduction was a
      prerequisite for this later conformational change. The MRAP-MC2R BRET approach
      provides a unique tool with which to analyze the activation of this receptor.

PMID- 21177831
TI  - Androgen receptor expression in the caput epididymal epithelium is essential for
      development of the initial segment and epididymal spermatozoa transit.
AB  - The epididymis plays an essential role in male fertility, and disruption of
      epididymal function can lead to obstructive azoospermia. Formation and function
      of the epididymis is androgen-dependent. The androgen receptor (AR) is expressed
      in both the stromal and epithelial compartments of the epididymis, and androgen
      action mediated via stromal cells is vital for its normal development and
      function. However the impact of epithelial specific AR-dependent signaling in the
      epididymis remains underexplored. To address this, we used conditional gene
      targeting in mice to selectively ablate AR from the caput epididymal epithelium,
      and characterized the resulting phenotype at multiple postnatal ages. Caput
      epithelium androgen receptor knock-out mice have normal serum testosterone
      concentrations at day (d) 21 and d100, but do not develop an epididymal initial
      segment. The remaining caput epithelium displays a significant decrease in
      epithelial cell height from d11 and lumen diameter from d21 and disruption of the
      smooth muscle layer of the caput epididymis at d100. From d21, caput epithelium
      androgen receptor knock-out mice accumulate cell debris, proteinaceous material,
      and, at later ages, spermatozoa in their efferent ducts, which prevents normal
      passage of spermatozoa from the testis into the cauda epididymis resulting in
      infertility when tested at d100. This efferent duct obstruction leads to fluid
      back-pressure and disruption of the seminiferous epithelium of the adult testis.
      We conclude that epithelial AR signaling is essential for postnatal development
      and function of the epididymal epithelium and that disruption of this signaling
      can contribute to obstructive azoospermia.

PMID- 21177830
TI  - Nebivolol attenuates redox-sensitive glomerular and tubular mediated proteinuria
      in obese rats.
AB  - Obesity and insulin resistance-related proteinuria is associated with oxidative
      stress and impaired tissue bioavailable nitric oxide. Recent data suggest that
      nicotinamide adenine dinucleotide phosphate oxidase-mediated oxidative injury to
      the proximal tubule, like that seen in the glomerulus, contributes to proteinuria
      in insulin-resistant states. The vasodilator beta-blocker nebivolol reduces
      nicotinamide adenine dinucleotide phosphate oxidase activity, increases
      bioavailable nitric oxide, and improves insulin sensitivity. To test the
      hypothesis that a treatment strategy that reduces oxidative stress and attenuates
      obesity-associated increases in glomerular and proximal tubule derived protein,
      we treated young Zucker obese (ZO) and age-matched Zucker lean male rats with
      nebivolol (10 mg . kg(-1) . d(-1)) for 21 d. Compared with Zucker lean, ZO
      controls exhibited increased proteinuria and gamma-glutamyl transpeptidase,
      reductions in systemic insulin sensitivity in association with increased renal
      renin, (pro)renin receptor, angiotensin II type 1 receptor, and mineralocorticoid
      receptor immunostaining, oxidative stress, and glomerular tubular structural
      abnormalities that were substantially improved with in vivo nebivolol treatment.
      Nebivolol treatment also led to improvements in glomerular podocyte foot-process
      effacement and improvement in podocyte-specific proteins (nephrin and
      synaptopodin) as well as proximal tubule-specific proteins (megalin and lysosomal
      associated membrane protein-2) and proximal tubule ultrastructural remodeling in
      the ZO kidney. Our findings support the notion that obesity and insulin
      resistance lead to increased glomerulotubular oxidative stress and resultant
      glomerular and tubular sources of excess urine protein. Furthermore, the results
      of this study suggest the beneficial effect of nebivolol on proteinuria was
      derived from improvements in weight and insulin sensitivity and reductions in
      renal oxidative stress in a state of obesity and insulin resistance.

PMID- 21177832
TI  - Reversal of endogenous dopamine receptor silencing in pituitary cells augments
      receptor-mediated apoptosis.
AB  - Dopamine (DA)-agonist targeting of the DA D(2) receptor (D2R) in prolactinomas is
      the first-line treatment choice for suppression of prolactin and induction of
      tumor shrinkage. Resistance to DA agonists seems to be related to receptor
      number. Using the MMQ and GH3 pituitary cell lines, that either do or do not
      express D2R, respectively, we explored the epigenetic profile associated with the
      presence or absence of D2R in these cells lines. These studies led us to explore
      pharmacological strategies designed to restore receptor expression and thereby
      potentially augment DA agonist-mediated apoptosis. We show in GH3 cells that the
      D2R harbors increased CpG island-associated methylation and enrichment for
      histone H3K27me3. Conversely, MMQ cells and normal pituitaries show enrichment
      for H3K9Ac and barely detectable H3K27me3. Coculture of GH3 cells with the
      demethylating agent zebularine and the histone deacetylase inhibitor trichostatin
      A was responsible for a decrease in CpG island methylation and enrichment for the
      histone H3K9Ac mark. In addition, challenge of GH3 cells with zebularine alone or
      coculture with both agents led to expression of endogenous D2R in these cells.
      Induced expression D2R in GH3 cells was associated with a significant increase in
      apoptosis indices to challenge with either DA or bromocriptine. Specificity of a
      receptor-mediated response was established in coincubations with specific D2R
      antagonist and siRNA approaches in GH3 cell and D2R expressing MMQ cell lines.
      These studies point to the potential efficacy of combined treatment with
      epigenetic drugs and DA agonists for the medical management of different
      pituitary tumor subtypes, resistant to conventional therapies.

PMID- 21177833
TI  - Integrin {alpha}3, but not {beta}1, regulates islet cell survival and function
      via PI3K/Akt signaling pathways.
AB  - beta1-integrin is a well-established regulator of beta-cell activities; however,
      the role of its associated alpha-subunits is relatively unknown. Previously, we
      have shown that human fetal islet and INS-1 cells highly express alpha3beta1
      integrin and that collagens I and IV significantly enhance their survival and
      function; in addition, blocking beta1 function in the fetal islet cells decreased
      adhesion on collagen I and increased apoptosis. The present study investigates
      the effect of blocking alpha3. Using alpha3 blocking antibody or small
      interfering RNA, the effects of alpha3-integrin blockade were examined in
      isolated human fetal or adult islet cells or INS-1 cells, cultured on collagens I
      or IV. In parallel, beta1 blockade was analyzed in INS-1 cells. Perturbing alpha3
      function in human islet or INS-1 cells resulted in significant decreases in cell
      function (adhesion, spreading, proliferation and Pdx1 and insulin
      expression/secretion), primarily on collagen IV. A significant decrease in focal
      adhesion kinase and ERK1/2 phosphorylation and increased caspase3 cleavage were
      observed on both collagens. These effects were similar to changes after beta1
      blockade. Interestingly, only alpha3 blockade reduced expression of phospho-Akt
      and members of its downstream signaling cascades (glycogen synthase kinase beta
      and X-linked inhibitor of apoptosis), demonstrating a specific effect of alpha3
      on the phosphatidylinositol 3-kinase/Akt pathway. These results suggest that
      alpha3- as well as beta1-integrin-extracellular matrix interactions are critical
      for modulating beta-cell survival and function through specialized signaling
      cascades and enhance our understanding of how to improve islet microenvironments
      for cell-based treatments of diabetes.

PMID- 21177834
TI  - Identification of prolactin-sensitive GABA and kisspeptin neurons in regions of
      the rat hypothalamus involved in the control of fertility.
AB  - High levels of circulating prolactin are known to cause infertility, but the
      precise mechanisms by which prolactin influences the neuroendocrine axis are yet
      to be determined. We used dual-label in situ hybridization to investigate whether
      prolactin-receptor (PRLR) mRNA is expressed in GnRH neurons. In addition, because
      gamma-aminobutyric acidergic and kisspeptin neurons in the rostral hypothalamus
      are known to regulate GnRH neurons and, hence, might mediate the actions of
      prolactin, we investigated whether these neurons coexpress PRLR mRNA. (35)S
      labeled RNA probes to detect PRLR mRNA were hybridized together with digoxigenin
      labeled probes to detect either GnRH, Gad1/Gad2, or Kiss1 mRNA in the rostral
      hypothalamus of ovariectomized (OVX), estradiol-treated rats. Additional sets of
      serial sections were cut through the arcuate nucleus of OVX rats, without
      estradiol replacement, to examine coexpression of PRLR mRNA in the arcuate
      population of kisspeptin neurons. PRLR mRNA was highly expressed throughout the
      rostral preoptic area, particularly in periventricular regions surrounding the
      third ventricle, and there was a high degree of colocalization of PRLR mRNA in
      both Gad1/Gad2 and Kiss1 mRNA-containing cells (86 and 85.5%, respectively). In
      contrast, only a small number of GnRH neurons (<5%) was found to coexpress PRLR
      mRNA. In the arcuate nucleus of OVX rats, the majority of Kiss1 mRNA-containing
      cells also coexpressed PRLR mRNA. These data are consistent with the hypothesis
      that, in addition to a direct action on a small subpopulation of GnRH neurons,
      prolactin actions on GnRH neurons are predominantly mediated indirectly, through
      known afferent pathways.

PMID- 21177835
TI  - The extracellular matrix component laminin promotes gap junction formation in the
      rat anterior pituitary gland.
AB  - Folliculo-stellate (FS) cells in the anterior pituitary gland are believed to
      have multifunctional properties. FS cells connect to each other not only by
      mechanical means, but also by gap junctional cell-to-cell communication. Using
      transgenic rats that express green fluorescent protein (GFP) specifically in FS
      cells in the anterior pituitary gland (S100b-GFP rats), we recently revealed that
      FS cells in primary culture markedly change their shape, and form numerous
      interconnections with neighboring FS cells in the presence of laminin, an
      extracellular matrix (ECM) component of the basement membrane. Morphological and
      functional changes in cells are believed to be partly modified by matricrine
      signaling, by which ECM components function as cellular signals. In the present
      study, we examined whether gap junction formation between FS cells is affected by
      matricrine cues. A cell sorter was used to isolate FS cells from male S100b-GFP
      rat anterior pituitary for primary culture. We observed that mRNA and protein
      levels of connexin 43 in gap junction channels were clearly higher in the
      presence of laminin. In addition, we confirmed the formation of gap junctions
      between FS cells in primary culture by electron microscopy. Interestingly, we
      also observed that FS cells in the presence of laminin displayed well-developed
      rough endoplasmic reticulum and Golgi apparatus. Our findings suggest that, in
      anterior pituitary gland, FS cells may facilitate functional roles such as gap
      junctional cell-to-cell communication by matricrine signaling.

PMID- 21177836
TI  - Idiopathic pulmonary arteriovenous malformations: clinical and imaging
      characteristics.
AB  - Pulmonary arteriovenous malformations (PAVMs) can cause stroke, brain abscess or
      life-threatening haemorrhage. Most PAVMs are associated with hereditary
      haemorrhagic telangiectasia (HHT). The aim of the present study was to describe
      the clinical presentation and treatment outcomes of those with idiopathic PAVMs,
      which has not previously been described in the literature. Patients with
      idiopathic PAVMs were identified at our HHT centre. Retrospective review of
      charts and imaging were performed. 20 patients were identified with idiopathic
      PAVMs. The most common symptoms reported were dyspnoea and migraines (50 and 30%
      of patients, respectively). Previous complications of PAVMs included haemoptysis
      (20%), stroke (20%) and brain abscess (5%). A total of 28 focal PAVMs were
      identified. Most patients (80%) had a solitary PAVM. 13 out of 28 PAVMs (46%)
      were located in the lower lobes. Most were simple and fistulous rather than
      complex and plexiform. Transcatheter embolotherapy was performed in 17 patients
      and was successful in improving oxygenation in all cases. The clinical
      manifestations and complications of idiopathic PAVMs are similar to those
      associated with HHT. Idiopathic PAVMs are anatomically similar to HHT-related
      PAVMs except for a greater number of solitary PAVMs and a lack of lower lobe
      predominance. Transcatheter embolotherapy is a safe and effective method for
      treating idiopathic PAVMs.

PMID- 21177837
TI  - Free fatty acids and the metabolic syndrome in patients with obstructive sleep
      apnoea.
AB  - Obesity and metabolic syndrome (MS) occur frequently in patients with obstructive
      sleep apnoea syndrome (OSAS). We hypothesised that circulating free fatty acids
      (FFAs) are elevated in OSAS patients independently of obesity. This elevation may
      contribute to the development of MS in these patients. We studied 119 OSAS
      patients and 119 controls. Participants were recruited and studied at sleep unit
      of our institution (Hospital Universitari Son Dureta, Palma de Mallorca, Spain)
      and were matched for sex, age and body mass index (BMI). The occurrence of MS was
      analysed by clinical criteria. Serum levels of FFAs, glucose, triglycerides,
      cholesterol, high-density lipoprotein-cholesterol, aspartate aminotransferase,
      alanine aminotransferase, gamma-glutamyltransferase, C-reactive protein and 8
      isoprostanes were determined. Prevalence of MS was higher in OSAS than in the
      control group (38 versus 21%; p=0.006). OSAS patients had higher FFAs levels than
      controls (mean+/-sd 12.2+/-4.9 versus 10.5+/-5.0 mg.dL(-1); p=0.015). Among
      subjects without MS, OSAS patients (OSAS+ MS-) showed higher levels of FFAs than
      controls (OSAS- MS-) (11.6+/-4.7 versus 10.0+/-4.4 mg.dL(-1); p=0.04). In a
      multiple regression model, after adjustment for age, sex, BMI and the presence of
      MS, FFAs were significantly associated with apnoea/hypopnoea index (p=0.04). This
      study shows that FFAs are elevated in OSAS and could be one of the mechanisms
      involved in the metabolic complications of OSAS.

PMID- 21177838
TI  - Reproducibility of 6-minute walking test in patients with COPD.
AB  - The reproducibility of the 6-min walking test (6MWT) needs to be more solidly
      studied. This study aimed to investigate the reproducibility of two 6MWTs
      performed on subsequent days in a large and representative sample of patients
      with chronic obstructive pulmonary disease (COPD), and to quantify the learning
      effect between the two tests, as well as its determinants. In a retrospective
      observational study, 1,514 patients with COPD performed two 6MWTs on subsequent
      days. Other measurements included body composition (dual X-ray absorptiometry),
      dyspnoea (Medical Research Council scale) and comorbidity (Charlson index).
      Although the 6MWT was reproducible (intraclass correlation coefficient = 0.93),
      patients walked farther in the second test (391 m, 95% CI 155-585 m versus 418 m,
      95% CI 185-605 m; p<0.0001). On average, the second 6MWT increased by 27 m (or
      7%), and 82% of patients improved in the second test. Determinants of improvement
      >= 42 m in the second test (upper limit of the clinically important change) were
      as follows: first 6MWT <350 m, Charlson index <2 and body mass index <30 kg . m(
      2) (OR 2.49, 0.76 and 0.60, respectively). The 6MWT was statistically
      reproducible in a representative sample of patients with COPD. However, the vast
      majority of patients improved significantly in the second test by an average
      learning effect of 27 m.

PMID- 21177839
TI  - The impact of using different symptom-based exacerbation algorithms in patients
      with COPD.
AB  - Not all exacerbations are captured by reliance on healthcare contacts. Symptom
      based exacerbation definitions have shown to provide more adequate measures of
      exacerbation rates, severity and duration. However, no consensus has been reached
      on what is the most useful method and algorithm to identify these events. This
      article provides an overview of the existing symptom-based definitions and tests
      the hypothesis that differences in exacerbation characteristics depend on the
      algorithms used. We systematically reviewed symptom-based methods and algorithms
      used in the literature, and quantified the impact of the four most referenced
      algorithms on exacerbation-related outcome using an existing chronic obstructive
      pulmonary disease (COPD) cohort (n = 137). We identified 51 studies meeting our
      criteria using 14 widely varying symptom algorithms to define onset, severity and
      recovery. The most (71%) frequently referenced algorithm (modified Anthonisen)
      identified an incidence rate of 1.7 episodes.patient-yr-1 (95% CI 1.4-2.1), while
      for requiring only one major or two major symptoms this was 1.9 episodes.patient
      yr-1 (95% CI 1.6-2.3) and 1.5 episodes.patient-yr-1 (95% CI 0.6-1.0),
      respectively. Studies were generally lacking methods to enhance validity and
      accuracy of symptom recording. This review revealed large inconsistencies in
      definitions, methods and accuracy to define symptom-based COPD exacerbations. We
      demonstrated that minor changes in symptom criteria substantially affect
      incidence rates, clustering type and classification of exacerbations.

PMID- 21177840
TI  - The respiratory health effects of nitrogen dioxide in children with asthma.
AB  - There is growing evidence that asthma symptoms can be aggravated or events
      triggered by exposure to indoor nitrogen dioxide (NO(2)) emitted from unflued gas
      heating. The impact of NO(2) on the respiratory health of children with asthma
      was explored as a secondary analysis of a randomised community trial, involving
      409 households during the winter period in 2006 (June to September). Geometric
      mean indoor NO(2) levels were 11.4 MUg . m(-3), while outdoor NO(2) levels were
      7.4 MUg . m(-3). Higher indoor NO(2) levels (per logged unit increase) were
      associated with greater daily reports of lower (mean ratio 14, 95% CI 1.12-1.16)
      and upper respiratory tract symptoms (mean ratio 1.03, 95% CI 1.00-1.05), more
      frequent cough and wheeze, and more frequent reliever use during the day, but had
      no effect on preventer use. Higher indoor NO(2) levels (per logged unit increase)
      were associated with a decrease in morning (-17.25 mL, 95% CI -27.63- -6.68) and
      evening (-13.21, 95% CI -26.03- -0.38) forced expiratory volume in 1 s readings.
      Outdoor NO(2) was not associated with respiratory tract symptoms, asthma
      symptoms, medication use or lung function measurements. These findings indicate
      that reducing NO(2) exposure indoors is important in improving the respiratory
      health of children with asthma.

PMID- 21177841
TI  - Long-term efficacy of bosentan in treatment of pulmonary arterial hypertension in
      children.
AB  - The aim of the present study was to evaluate a 5-yr experience of bosentan in
      children with pulmonary arterial hypertension (PAH). A retrospective,
      observational study was made of children in the UK Pulmonary Hypertension Service
      for Children (Great Ormond Street Hospital for Children, London, UK) who were
      given bosentan as monotherapy or in combination, from February 2002 to May 2008
      and followed up for >= 6 months. Detailed studies were made of 101 children with
      idiopathic PAH (IPAH) (n = 42) and PAH associated with congenital heart disease
      (n = 59). Before treatment, World Health Organization (WHO) functional class, 6
      min walk distance (6MWD), height, weight and haemodynamic data were determined.
      Evaluations were analysed after 6 months and annually to a maximum of 5 yrs.
      Median duration of treatment was 31.5 months. Initial improvement in WHO
      functional class and 6MWD was maintained for up to 3 yrs. Height and weight
      increased but the z-scores did not improve. After 3 yrs, bosentan was continued
      as monotherapy in only 21% of children with IPAH, but in 69% of repaired cases
      and 56% of those with Eisenmenger syndrome. The Kaplan-Meier survival estimates
      for the 101 patients were 96, 89, 83 and 60% at 1, 2, 3 and 5 yrs, respectively.
      A treatment regime that includes bosentan is safe and appears to be effective in
      slowing disease progression in children with PAH.

PMID- 21177842
TI  - Parameters affecting pharyngeal response to genioglossus stimulation in sleep
      apnoea.
AB  - Chronic stimulation of the hypoglossus nerve may provide a new treatment modality
      for obstructive sleep apnoea (OSA). In previous studies we observed large
      differences in response to stimulation of the genioglossus (GG). We hypothesised
      that both individual patient characteristics and the area of the GG stimulated
      are responsible for these differences. In the present study, we compared the
      response to GG electrical stimulation at the anterior area (GGa-ES), which
      activates the whole GG and the posterior area (GGp-ES), which activates
      preferentially the longitudinal fibres. Studies were performed in 14 propofol
      sedated OSA patients. The parameters evaluated included cephalometry, pressure
      flow relationship and pharyngeal shape and compliance assessed by pharyngoscopy.
      Compared with GGa-ES, GGp-ES resulted in significantly larger decreases in the
      critical value of end-expiratory pressure (P(crit)) (from 3.8 +/- 2.2 to 2.9 +/-
      3.3 and -2.0 +/- 3.9 cmH(2)O, respectively (p<0.001)). Both tongue size and
      velopharyngeal shape (anteroposterior to lateral ratio) correlated significantly
      with the decrease in P(crit) during GGp-ES (R = 0.53 and -0.66, respectively;
      p<0.05). In the patients with the larger tongue size (n = 7), the decrease in
      P(crit) reached 8.0 +/- 2.2 cmH(2)O during GGp-ES. We conclude that directing
      stimulation to longitudinal fibres of the GG improves the flow-mechanical effect.
      In addition, patients with large tongues and narrow pharynx tend to respond
      better to GGp-ES.

PMID- 21177843
TI  - Asthma and comorbid medical illness.
AB  - Asthma is associated with several comorbidities but the magnitude of the
      association has not been clearly defined. We aimed to examine the relationship
      between asthma and comorbidities using information obtained from the Health
      Search Database (HSD) owned by the Italian College of General Practitioners
      (Societa Italiana Medici Generici, Florence, Italy). We conducted a population
      based retrospective study using information obtained from the HSD. The software
      system used codes of all the diagnostic records using the 9th revision of the
      International Classification of Diseases. Asthma appeared to be weakly associated
      with cardiovascular and hypertensive diseases. Intriguingly, the odds ratio of
      acute or old myocardial infarction was 0.84 (95% CI 0.77-0.91). Asthma was also
      weakly associated with depression, diabetes mellitus, dyslipidaemia, osteoporosis
      and rhinosinusitis. In contrast, it was strongly associated with gastro
      oesophageal reflux disease (GORD) and, particularly, allergic rhinitis. Age did
      not influence the association of asthma with comorbidities whereas sex had a
      different impact according to the specific comorbidity. Our results indicate that
      asthma is weakly associated with several comorbidities, whereas its association
      with allergic rhinitis or GORD is stronger.

PMID- 21177844
TI  - Periostin, a matrix protein, is a novel biomarker for idiopathic interstitial
      pneumonias.
AB  - Idiopathic interstitial pneumonias (IIPs) are histopathologically classified into
      several types, including usual interstitial pneumonia (UIP), nonspecific
      interstitial pneumonia (NSIP) and cryptogenic organising pneumonia (COP). We
      investigated whether periostin, a matrix protein, could be used as a biomarker to
      assess histopathological types of IIPs. We performed immunohistochemical analyses
      in each histopathological type of IIP, examined serum levels of periostin in IIP
      patients and analysed the relationship between serum levels of periostin and the
      pulmonary functions in patients with idiopathic pulmonary fibrosis (IPF).
      Periostin was strongly expressed in lungs of UIP and fibrotic NSIP patients,
      whereas expression of periostin was weak in the lungs of cellular NSIP and COP
      patients, as well as in normal lungs. Serum levels of periostin in IPF were
      significantly higher than those of healthy subjects and COP patients.
      Furthermore, periostin levels in IPF patients were inversely correlated with
      their pulmonary functions. Thus, we have found that periostin is a novel
      component of fibrosis in IIP. Periostin may be a potential biomarker to
      distinguish IIP with fibrosis.

PMID- 21177845
TI  - Series "matrix metalloproteinases in lung health and disease": Biological role of
      matrix metalloproteinases: a critical balance.
AB  - Matrix metalloproteinases (MMPs) are members of the metzincin group of proteases
      which share the conserved zinc-binding motif in their catalytic active site. It
      was originally thought that their main function is to degrade the various
      components of the extracellular matrix (ECM), yet recent studies have led us to
      appreciate their significance as regulators of extracellular tissue signalling
      networks. Due to the broad spectrum of their substrate specificity, MMPs
      contribute to the homeostasis of many tissues and participate in several
      physiological processes, such as bone remodelling, angiogenesis, immunity and
      wound healing. MMP activity is tightly controlled at the level of transcription,
      pro-peptide activation and inhibition by tissue inhibitors of MMPs. Dysregulated
      MMP activity leads to pathological conditions such as arthritis, inflammation and
      cancer, thus highlighting MMPs as promising therapeutic targets. Analysis of MMP
      mutant mice has proved to be an essential tool for the identification of novel
      functions and interactions of single MMP members. Advancing our understanding of
      the MMP contribution to tissue homeostasis will lead us to identify causal
      relationships between their dysregulation and the development of disease
      pathologies, thus guiding us to successful MMP-directed therapies.

PMID- 21177846
TI  - Lung function, radiological changes and exposure: analysis of ATSDR data from
      Libby, MT, USA.
AB  - In 2000, the Agency for Toxic Substances and Disease Registry (ATSDR; Atlanta,
      GA, USA) investigated lung disease in those exposed to the tremolite-contaminated
      vermiculite mine in Libby, MT, USA. Previously unreported spirometric results are
      presented here in relation to exposure and radiographic findings. 4,524 study
      participants were assigned to one of seven mutually exclusive exposure
      categories. Associations among radiographic findings, spirometric results and
      exposure were investigated, along with the effect of a reduction in exposure
      potential when production was moved to a wet process mill in the mid 1970s.
      Spirometry data for the total population by smoking status and age were within
      the normal range. Prevalence of pleural plaque increased with age, but was lowest
      in the environmentally exposed group (0.42-12.74%) and greatest in the W.R. Grace
      & Co. mineworkers (20-45.68%). For males, there was a significant (4.5%) effect
      of pleural plaques on forced vital capacity. For W.R. Grace & Co. workers and
      household contacts, a reduction in plaque (0.11 versus 1.64%) and in diffuse
      pleural thickening or costophrenic angle obliteration (1.94 and 0.13%) was noted
      for those exposed after 1976. These analyses do not support a clinically
      important reduction in spirometry of this cohort. The 1976 reductions in exposure
      have led to decrease in radiographic changes.

PMID- 21177847
TI  - An essential role of the cysteine-rich domain of FZD4 in Norrin/Wnt signaling and
      familial exudative vitreoretinopathy.
AB  - The Wnt pathway plays important yet diverse roles in health and disease.
      Mutations in the Wnt receptor FZD4 gene have been confirmed to cause familial
      exudative vitreoretinopathy (FEVR). FEVR is characterized by incomplete
      vascularization of the peripheral retina, which can lead to vitreous bleeding,
      tractional retinal detachment, and blindness. We screened for mutations in the
      FZD4 gene in five families with FEVR and identified five mutations (C45Y, Y58C,
      W226X, C204R, and W496X), including three novel mutations (C45Y, Y58C, and
      W226X). In the retina, Norrin serves as a ligand and binds to FZD4 to activate
      the Wnt signaling pathway in normal angiogenesis and vascularization. The
      cysteine-rich domain (CRD) of FZD4 has been shown to play a critical role in
      Norrin-FZD4 binding. We investigated the effect of mutations in the FZD4 CRD in
      Norrin binding and signaling in vitro and in vivo. Wild-type and mutant FZD4
      proteins were assayed for Norrin binding and Norrin-dependent activation of the
      canonical Wnt pathway by cell-surface and overlay binding assays and luciferase
      reporter assays. In HEK293 transfection studies, C45Y, Y58C, and C204R mutants
      did not bind to Norrin and failed to transduce FZD4-mediated Wnt/beta-catenin
      signaling. In vivo studies using Xenopus embryos showed that these FZD4 mutations
      disrupt Norrin/beta-catenin signaling as evidenced by decreased Siamois and Xnr3
      expression. This study identified a new class of FZD4 gene mutations in human
      disease and demonstrates a critical role of the CRD in Norrin binding and
      activation of the beta-catenin pathway.

PMID- 21177848
TI  - Structure-functional analyses of CRHSP-24 plasticity and dynamics in oxidative
      stress response.
AB  - The cold shock domain (CSD) is an evolutionarily conserved nucleic acid binding
      domain that exhibits binding activity to RNA, ssDNA, and dsDNA. Mammalian CRHSP
      24 contains CSD, but its structure-functional relationship has remained elusive.
      Here we report the crystal structure of human CRHSP-24 and characterization of
      the molecular trafficking of CRHSP-24 between stress granules and processing
      bodies in response to oxidative stress. The structure of CRHSP-24 determined by
      single-wavelength anomalous dispersion exhibits an alpha-helix and a compact beta
      barrel formed by five curved anti-parallel beta strands. Ligand binding activity
      of the CSD is orchestrated by residues Ser(41) to Leu(43). Interestingly, a
      phosphomimetic S41D mutant abolishes the ssDNA binding in vitro and causes CRHSP
      24 liberated from stress granules in vivo without apparent alternation of its
      localization to the processing bodies. This new class of phosphorylation
      regulated interaction between the CSD and nucleic acids is unique in stress
      granule plasticity. Importantly, the association of CRHSP-24 with stress granules
      is blocked by PP4/PP2A inhibitor calyculin A as PP2A catalyzes the
      dephosphorylation of Ser(41) of CRHSP-24. Therefore, we speculate that CRHSP-24
      participates in oxidative stress response via a dynamic and temporal association
      between stress granules and processing bodies.

PMID- 21177849
TI  - Regulation of Kruppel-like factor 4 by the anaphase promoting complex pathway is
      involved in TGF-beta signaling.
AB  - Kruppel-like factor 4 (KLF4), a zinc finger-containing transcriptional factor,
      regulates a variety of biological processes, including cell proliferation,
      differentiation, apoptosis, and stem cell reprogramming. Post-translational
      modifications of KLF4, including phosphorylation, acetylation, and sumoylation,
      regulate its transcriptional activity. Most recent studies also demonstrate that
      KLF4 is targeted for ubiquitin-dependent proteolysis during cell cycle
      progression. However, the underlying mechanism remains largely unknown. In this
      study, we demonstrated that KLF4 is profoundly degraded in response to TGF-beta
      signaling. We have identified the Cdh1-anaphase promoting complex as a putative
      E3 ligase that governs TGF-beta-induced KLF4 degradation. The TGF-beta-induced
      KLF4 degradation is mediated by the destruction box on the KLF4. Either depletion
      of Cdh1 by RNA interference or stabilization of KLF4 by disruption of its
      destruction box significantly attenuates TGF-beta-induced ubiquitylation and
      degradation. In addition, depletion of Cdh1 or stabilization of KLF4 antagonizes
      TGF-beta-induced activation of transcription. Determining the role of KLF4
      proteolysis in response to TGF-beta signaling has opened a new perspective to
      understand the TGF-beta signaling pathway.

PMID- 21177850
TI  - Arrangement and mobility of the voltage sensor domain in prokaryotic voltage
      gated sodium channels.
AB  - Prokaryotic voltage-gated sodium channels (Na(V)s) form homotetramers with each
      subunit contributing six transmembrane alpha-helices (S1-S6). Helices S5 and S6
      form the ion-conducting pore, and helices S1-S4 function as the voltage sensor
      with helix S4 thought to be the essential element for voltage-dependent
      activation. Although the crystal structures have provided insight into voltage
      gated K channels (K(V)s), revealing a characteristic domain arrangement in which
      the voltage sensor domain of one subunit is close to the pore domain of an
      adjacent subunit in the tetramer, the structural and functional information on
      Na(V)s remains limited. Here, we show that the domain arrangement in NaChBac, a
      firstly cloned prokaryotic Na(V), is similar to that in K(V)s. Cysteine
      substitutions of three residues in helix S4, Q107C, T110C, and R113C, effectively
      induced intersubunit disulfide bond formation with a cysteine introduced in helix
      S5, M164C, of the adjacent subunit. In addition, substituting two acidic residues
      with lysine, E43K and D60K, shifted the activation of the channel to more
      positive membrane potentials and consistently shifted the preferentially formed
      disulfide bond from T110C/M164C to Q107C/M164C. Because Gln-107 is located closer
      to the extracellular side of helix S4 than Thr-110, this finding suggests that
      the functional shift in the voltage dependence of activation is related to a
      restriction of the position of helix S4 in the lipid bilayer. The domain
      arrangement and vertical mobility of helix S4 in NaChBac indicate that the
      structure and the mechanism of voltage-dependent activation in prokaryotic Na(V)s
      are similar to those in canonical K(V)s.

PMID- 21177851
TI  - Identification of a novel hemolymph peptide that modulates silkworm feeding
      motivation.
AB  - Phytophagous insects do not constantly chew their diets; most of their time is
      spent in a non-feeding quiescent state even though they live on or around their
      diets. Following starvation, phytophagous insect larvae exhibit enhanced foraging
      behaviors such as nibbling and walking similar to the sequential behavior that
      occurs prior to each meal. Although extensive physiological studies have revealed
      regularly occurring feeding behaviors in phytophagous insects, little has been
      elucidated regarding the mechanism at the molecular level. Here, we report
      identification and characterization of a novel 62-amino acid peptide, designated
      as hemolymph major anionic peptide (HemaP), from the hemolymph of Bombyx mori
      larvae that induces foraging behaviors. The endogenous HemaP levels are
      significantly increased by diet deprivation, whereas refeeding after starvation
      returns them to basal levels. In larvae fed ad libitum, hemolymph HemaP levels
      fluctuate according to the feeding cycle, indicating that locomotor-associated
      feeding behaviors of B. mori larvae are initiated when HemaP levels exceed an
      unidentified threshold. Furthermore, administration of exogenous HemaP mimics the
      starvation-experienced state by affecting dopamine levels in the suboesophageal
      ganglion, which coordinates neck and mandible movements. These data strongly
      suggest that fluctuation of hemolymph HemaP levels modulates the regularly
      occurring feeding-motivated behavior in B. mori by triggering feeding initiation.

PMID- 21177852
TI  - Glutathione transferases of Phanerochaete chrysosporium: S-glutathionyl-p
      hydroquinone reductase belongs to a new structural class.
AB  - The white rot fungus Phanerochaete chrysosporium, a saprophytic basidiomycete,
      possesses a large number of cytosolic glutathione transferases, eight of them
      showing similarity to the Omega class. PcGSTO1 (subclass I, the bacterial
      homologs of which were recently proposed, based on their enzymatic function, to
      constitute a new class of glutathione transferase named S-glutathionyl
      (chloro)hydroquinone reductases) and PcGSTO3 (subclass II related to mammalian
      homologs) have been investigated in this study. Biochemical investigations
      demonstrate that both enzymes are able to catalyze deglutathionylation reactions
      thanks to the presence of a catalytic cysteinyl residue. This reaction leads to
      the formation of a disulfide bridge between the conserved cysteine and the
      removed glutathione from their substrate. The substrate specificity of each
      isoform differs. In particular PcGSTO1, in contrast to PcGSTO3, was found to
      catalyze deglutathionylation of S-glutathionyl-p-hydroquinone substrates. The
      three-dimensional structure of PcGSTO1 presented here confirms the hypothesis
      that it belongs not only to a new biological class but also to a new structural
      class that we propose to name GST xi. Indeed, it shows specific features, the
      most striking ones being a new dimerization mode and a catalytic site that is
      buried due to the presence of long loops and that contains the catalytic
      cysteine.

PMID- 21177853
TI  - Analysis of heterotropic cooperativity in cytochrome P450 3A4 using alpha
      naphthoflavone and testosterone.
AB  - Cytochrome P450 3A4 (CYP3A4) displays non-Michaelis-Menten kinetics for many of
      the substrates it metabolizes, including testosterone (TST) and alpha
      naphthoflavone (ANF). Heterotropic effects between these two substrates can
      further complicate the metabolic profile of the enzyme. In this work, monomeric
      CYP3A4 solubilized in Nanodiscs has been studied for its ability to interact with
      varying molar ratios of ANF and TST. Comparison of the observed heme spin state,
      NADPH consumption, and product formation rates with a non-cooperative model
      calculated from a linear combination of the global analysis of each substrate
      reveals a detailed landscape of the heterotropic interactions and indicates
      negligible binding cooperativity between ANF and TST. The observed effect of ANF
      on the kinetics of TST metabolism is due to the additive action of the second
      substrate with no specific allosteric effects.

PMID- 21177854
TI  - The structure of the human RNase H2 complex defines key interaction interfaces
      relevant to enzyme function and human disease.
AB  - Ribonuclease H2 (RNase H2) is the major nuclear enzyme involved in the
      degradation of RNA/DNA hybrids and removal of ribonucleotides misincorporated in
      genomic DNA. Mutations in each of the three RNase H2 subunits have been
      implicated in a human auto-inflammatory disorder, Aicardi-Goutieres Syndrome
      (AGS). To understand how mutations impact on RNase H2 function we determined the
      crystal structure of the human heterotrimer. In doing so, we correct several key
      regions of the previously reported murine RNase H2 atomic model and provide
      biochemical validation for our structural model. Our results provide new insights
      into how the subunits are arranged to form an enzymatically active complex. In
      particular, we establish that the RNASEH2A C terminus is a eukaryotic adaptation
      for binding the two accessory subunits, with residues within it required for
      enzymatic activity. This C-terminal extension interacts with the RNASEH2C C
      terminus and both are necessary to form a stable, enzymatically active
      heterotrimer. Disease mutations cluster at this interface between all three
      subunits, destabilizing the complex and/or impairing enzyme activity. Altogether,
      we locate 25 out of 29 residues mutated in AGS patients, establishing a firm
      basis for future investigations into disease pathogenesis and function of the
      RNase H2 enzyme.

PMID- 21177855
TI  - Efficient and rapid nucleosome traversal by RNA polymerase II depends on a
      combination of transcript elongation factors.
AB  - The nucleosome is generally found to be a strong barrier to transcript elongation
      by RNA polymerase II (pol II) in vitro. The elongation factors TFIIF and TFIIS
      have been shown to cooperate in maintaining pol II in the catalytically competent
      state on pure DNA templates. We now show that although TFIIF or TFIIS alone is
      modestly stimulatory for nucleosome traversal, both factors together increase
      transcription through nucleosomes in a synergistic manner. We also studied the
      effect of TFIIF and TFIIS on transcription of nucleosomes containing a Sin mutant
      histone. The Sin point mutations reduce critical histone-DNA contacts near the
      center of the nucleosome. Significantly, we found that nucleosomes with a Sin
      mutant histone are traversed to the same extent and at nearly the same rate as
      equivalent pure DNA templates if both TFIIS and TFIIF are present. Thus, the
      nucleosome is not necessarily an insurmountable barrier to transcript elongation
      by pol II. If unfolding of template DNA from the nucleosome surface is
      facilitated and the tendency of pol II to retreat from barriers is countered,
      transcription of nucleosomal templates can be rapid and efficient.

PMID- 21177856
TI  - Protein kinase A-alpha directly phosphorylates FoxO1 in vascular endothelial
      cells to regulate expression of vascular cellular adhesion molecule-1 mRNA.
AB  - FoxO1, a forkhead box O class transcription factor, is abundant in insulin
      responsive tissues. Akt, downstream from phosphatidylinositol 3-kinase in insulin
      signaling, phosphorylates FoxO1 at Thr(24), Ser(256), and Ser(319), negatively
      regulating its function. We previously reported that dehydroepiandrosterone
      stimulated phosphorylation of FoxO1 in endothelial cells requires cAMP-dependent
      protein kinase alpha (PKA-alpha). Therefore, we hypothesized that FoxO1 is a
      novel direct substrate for PKA-alpha. Using an immune complex kinase assay with
      [gamma-(32)P]ATP, purified PKA-alpha directly phosphorylated wild-type FoxO1 but
      not FoxO1-AAA (mutant with alanine substitutions at known Akt phosphorylation
      sites). Phosphorylation of wild-type FoxO1 (but not FoxO1-AAA) was detectable
      using phospho-specific antibodies. Similar results were obtained using purified
      GST-FoxO1 protein as the substrate. Thus, FoxO1 is a direct substrate for PKA
      alpha in vitro. In bovine aortic endothelial cells, interaction between
      endogenous PKA-alpha and endogenous FoxO1 was detected by co-immunoprecipitation.
      In human aortic endothelial cells (HAEC), pretreatment with H89 (PKA inhibitor)
      or siRNA knockdown of PKA-alpha decreased forskolin- or prostaglandin E(2)
      stimulated phosphorylation of FoxO1. In HAEC transfected with a FoxO-promoter
      luciferase reporter, co-expression of the catalytic domain of PKA-alpha,
      catalytically inactive mutant PKA-alpha, or siRNA against PKA-alpha caused
      corresponding increases or decreases in transactivation of the FoxO promoter.
      Expression of vascular cellular adhesion molecule-1 mRNA, up-regulated by FoxO1
      in endothelial cells, was enhanced by siRNA knockdown of PKA-alpha or treatment
      of HAEC with the PKA inhibitor H89. Adhesion of monocytes to endothelial cells
      was enhanced by H89 treatment or overexpression of FoxO1-AAA, similar to effects
      of TNF-alpha treatment. We conclude that FoxO1 is a novel physiological substrate
      for PKA-alpha in vascular endothelial cells.

PMID- 21177857
TI  - PI3K-mTORC1 attenuates stress response by inhibiting cap-independent Hsp70
      translation.
AB  - Protein synthesis is a key regulated cellular process that links nutrient
      availability and organismal growth. It has long been known that some cellular
      proteins continue to be synthesized under conditions where global translation is
      severely compromised. One prominent example is the selective translation of heat
      shock proteins (Hsps) under stress conditions. Although the transcriptional
      regulation of Hsp genes has been well established, neither the specific
      translation-promoting features nor the regulatory mechanism of the translation
      machinery have been clearly defined. Here we show that the stress-induced
      preferential translation of Hsp70 mRNA is negatively regulated by PI3K-mTORC1
      signaling. Despite the transcriptional up-regulation, the translation of Hsp70
      mRNA is deficient in cells lacking tuberous sclerosis complex 2. Conversely,
      Hsp70 synthesis is enhanced under the reduced PI3K-mTORC1 signaling. We found
      that the 5' UTR of Hsp70 mRNA contributes to cap-independent translation without
      exhibiting typical features of internal ribosome entry site. Our findings imply a
      plausible mechanism for how persistent PI3K-mTORC1 signaling favors the
      development of age-related pathologies by attenuating stress resistance.

PMID- 21177858
TI  - The structural and biochemical characterization of human RNase H2 complex reveals
      the molecular basis for substrate recognition and Aicardi-Goutieres syndrome
      defects.
AB  - RNase H2 cleaves RNA sequences that are part of RNA/DNA hybrids or that are
      incorporated into DNA, thus, preventing genomic instability and the accumulation
      of aberrant nucleic acid, which in humans induces Aicardi-Goutieres syndrome, a
      severe autoimmune disorder. The 3.1 A crystal structure of human RNase H2
      presented here allowed us to map the positions of all 29 mutations found in
      Aicardi-Goutieres syndrome patients, several of which were not visible in the
      previously reported mouse RNase H2. We propose the possible effects of these
      mutations on the protein stability and function. Bacterial and eukaryotic RNases
      H2 differ in composition and substrate specificity. Bacterial RNases H2 are
      monomeric proteins and homologs of the eukaryotic RNases H2 catalytic subunit,
      which in addition possesses two accessory proteins. The eukaryotic RNase H2
      heterotrimeric complex recognizes RNA/DNA hybrids and (5')RNA-DNA(3')/DNA
      junction hybrids as substrates with similar efficiency, whereas bacterial RNases
      H2 are highly specialized in the recognition of the (5')RNA-DNA(3') junction and
      very poorly cleave RNA/DNA hybrids in the presence of Mg(2+) ions. Using the
      crystal structure of the Thermotoga maritima RNase H2-substrate complex, we
      modeled the human RNase H2-substrate complex and verified the model by mutational
      analysis. Our model indicates that the difference in substrate preference stems
      from the different position of the crucial tyrosine residue involved in substrate
      binding and recognition.

PMID- 21177859
TI  - hALP, a novel transcriptional U three protein (t-UTP), activates RNA polymerase I
      transcription by binding and acetylating the upstream binding factor (UBF).
AB  - Transcription of ribosome RNA precursor (pre-rRNA) and pre-rRNA processing are
      coordinated by a subset of U three proteins (UTPs) known as transcriptional UTPs
      (t-UTPs), which participate in pre-rRNA transcription in addition to
      participation in 18 S rRNA processing. However, the mechanism by which t-UTPs
      function in pre-rRNA transcription remains undetermined. In the present study, we
      identified hALP, a histone acetyl-transferase as a novel t-UTP. We first showed
      that hALP is nucleolar, and is associated with U3 snoRNA and required for 18 S
      rRNA processing. Moreover, depletion of hALP resulted in a decreased level of 47
      S pre-rRNA. Ectopic expression of hALP activated the rDNA promoter luciferase
      reporter and knockdown of hALP inhibited the reporter. In addition, hALP bound
      rDNA. Taken together these data identify hALP as a novel t-UTP.
      Immunoprecipitation and GST pulldown experiments showed that hALP binds the
      upstream binding factor (UBF) in vivo and in vitro. It is of importance that hALP
      acetylated UBF depending on HAT in vivo, and hALP but not hALP (DeltaHAT)
      facilitated the nuclear translocation of the RNA polymerase I (Pol I)-associated
      factor 53 (PAF53) from the cytoplasm and promoted the association of UBF with
      PAF53. Thus, we provide a mechanism in which a novel t-UTP activates Pol I
      transcription by binding and acetylating UBF.

PMID- 21177860
TI  - Losac, the first hemolin that exhibits procogulant activity through selective
      factor X proteolytic activation.
AB  - Envenoming by the contact of human skin with Lonomia obliqua caterpillars
      promotes a hemorrhagic syndrome characterized by a consumptive coagulopathy.
      Losac (Lonomia obliqua Stuart factor activator) is a component of the bristle of
      L. obliqua that is probably partially responsible for the observed syndrome
      because it activates factor X and is recognized by an effective antilonomic
      serum. Here we unveil the proteolytic activity of Losac and demonstrate the
      feasibility of its recombinant production. On the other hand, Losac has no
      homology to known proteases, but it can be inhibited by PMSF, a serine protease
      inhibitor. Instead, it shows closer homology to members of the hemolin family of
      proteins, a group of cell adhesion molecules. The recombinant protein (rLosac)
      shortened the coagulation time of normal and deficient plasmas, whereas it was
      ineffective in factor X-deficient plasma unless reconstituted with this protein.
      rLosac was able to activate factor X in a dose- and time-dependent manner but not
      gamma-carboxyglutamic acid domainless factor X. Moreover, phospholipids and
      calcium ions increased rLosac activity. Also, rLosac had no effect on fibrin or
      fibrinogen, indicating its specificity for blood coagulation activation. Linear
      double reciprocal plots indicate that rLosac follows a Michaelis-Menten kinetics.
      Cleavage of factor X by rLosac resulted in fragments that are compatible with
      those generated by RVV-X (a well known factor X activator). Together, our results
      validate Losac as the first protein from the hemolin family exhibiting
      procoagulant activity through selective proteolysis on coagulation factor X.

PMID- 21177861
TI  - Calreticulin is a thermostable protein with distinct structural responses to
      different divalent cation environments.
AB  - Calreticulin is a soluble calcium-binding chaperone of the endoplasmic reticulum
      (ER) that is also detected on the cell surface and in the cytosol. Calreticulin
      contains a single high affinity calcium-binding site within a globular domain and
      multiple low affinity sites within a C-terminal acidic region. We show that the
      secondary structure of calreticulin is remarkably thermostable at a given calcium
      concentration. Rather than corresponding to complete unfolding events, heat
      induced structural transitions observed for calreticulin relate to tertiary
      structural changes that expose hydrophobic residues and reduce protein rigidity.
      The thermostability and the overall secondary structure content of calreticulin
      are impacted by the divalent cation environment, with the ER range of calcium
      concentrations enhancing stability, and calcium-depleting or high calcium
      environments reducing stability. Furthermore, magnesium competes with calcium for
      binding to calreticulin and reduces thermostability. The acidic domain of
      calreticulin is an important mediator of calcium-dependent changes in secondary
      structure content and thermostability. Together, these studies indicate
      interactions between the globular and acidic domains of calreticulin that are
      impacted by divalent cations. These interactions influence the structure and
      stability of calreticulin, and are likely to determine the multiple functional
      activities of calreticulin in different subcellular environments.

PMID- 21177862
TI  - Roles of two activation domains in Zap1 in the response to zinc deficiency in
      Saccharomyces cerevisiae.
AB  - Previous studies suggested that the zinc-responsive Zap1 transcriptional
      activator directly regulates the expression of over 80 genes in Saccharomyces
      cerevisiae. Many of these genes play key roles to enhance the ability of yeast
      cells to grow under zinc-limiting conditions. Zap1 is unusual among
      transcriptional activators in that it contains two activation domains, designated
      AD1 and AD2, which are regulated independently by zinc. These two domains are
      evolutionarily conserved among Zap1 orthologs suggesting that they are both
      important for Zap1 function. In this study, we have examined the roles of AD1 and
      AD2 in low zinc growth and the regulation of Zap1 target gene expression. Using
      alleles that are specifically disrupted for either AD1 or AD2 function, we found
      that these domains are not redundant, and both are important for normal growth in
      low zinc. AD1 plays the primary role in zinc-responsive gene regulation, whereas
      AD2 is required for maximal expression of only a few target promoters. AD1 alone
      is capable of driving full expression of most Zap1 target genes and dictates the
      kinetics of Zap1 gene induction in response to zinc withdrawal. Surprisingly, we
      found that AD1 is less active in zinc-limited cells under heat stress and AD2
      plays a more important role under those conditions. These results suggest that
      AD2 may contribute more to Zap1 function when zinc deficiency is combined with
      other environmental stresses. In the course of these studies, we also found that
      the heat shock response is induced under conditions of severe zinc deficiency.

PMID- 21177863
TI  - S100P is a novel interaction partner and regulator of IQGAP1.
AB  - Ca(2+)-binding proteins of the S100 family participate in intracellular Ca(2+)
      signaling by binding to and regulating specific cellular targets in their Ca(2+)
      loaded conformation. Because the information on specific cellular targets of
      different S100 proteins is still limited, we developed an affinity approach that
      selects for protein targets only binding to the physiologically active dimer of
      an S100 protein. Using this approach, we here identify IQGAP1 as a novel and
      dimer-specific target of S100P, a member of the S100 family enriched in the
      cortical cytoskeleton. The interaction between S100P and IQGAP1 is strictly
      Ca(2+)-dependent and characterized by a dissociation constant of 0.2 MUM. Binding
      occurs primarily through the IQ domain of IQGAP1 and the first EF hand loop of
      S100P, thus representing a novel structural principle of S100-target protein
      interactions. Upon cell stimulation, S100P and IQGAP1 co-localize at or in close
      proximity to the plasma membrane, and complex formation can be linked to altered
      signal transduction properties of IQGAP1. Specifically, the EGF-induced tyrosine
      phosphorylation of IQGAP1 that is thought to function in assembling signaling
      intermediates at IQGAP1 scaffolds in the subplasmalemmal region is markedly
      reduced in cells overexpressing S100P but not in cells expressing an S100P mutant
      deficient in IQGAP1 binding. Furthermore, B-Raf binding to IQGAP1 and MEK1/2
      activation occurring downstream of IQGAP1 in EGF-triggered signaling cascades are
      compromised at elevated S100P levels. Thus, S100P is a novel Ca(2+)-dependent
      regulator of IQGAP1 that can down-regulate the function of IQGAP1 as a signaling
      intermediate by direct interaction.

PMID- 21177864
TI  - Nanomechanics of the cadherin ectodomain: "canalization" by Ca2+ binding results
      in a new mechanical element.
AB  - Cadherins form a large family of calcium-dependent cell-cell adhesion receptors
      involved in development, morphogenesis, synaptogenesis, differentiation, and
      carcinogenesis through signal mechanotransduction using an adaptor complex that
      connects them to the cytoskeleton. However, the molecular mechanisms underlying
      mechanotransduction through cadherins remain unknown, although their
      extracellular region (ectodomain) is thought to be critical in this process. By
      single molecule force spectroscopy, molecular dynamics simulations, and protein
      engineering, here we have directly examined the nanomechanics of the C-cadherin
      ectodomain and found it to be strongly dependent on the calcium concentration. In
      the presence of calcium, the ectodomain extends through a defined ("canalized")
      pathway that involves two mechanical resistance elements: a mechanical clamp from
      the cadherin domains and a novel mechanostable component from the interdomain
      calcium-binding regions ("calcium rivet") that is abolished by magnesium
      replacement and in a mutant intended to impede calcium coordination. By contrast,
      in the absence of calcium, the mechanical response of the ectodomain becomes
      largely "decanalized" and destabilized. The cadherin ectodomain may therefore
      behave as a calcium-switched "mechanical antenna" with very different mechanical
      responses depending on calcium concentration (which would affect its mechanical
      integrity and force transmission capability). The versatile mechanical design of
      the cadherin ectodomain and its dependence on extracellular calcium facilitate a
      variety of mechanical responses that, we hypothesize, could influence the various
      adhesive properties mediated by cadherins in tissue morphogenesis, synaptic
      plasticity, and disease. Our work represents the first step toward the mechanical
      characterization of the cadherin system, opening the door to understanding the
      mechanical bases of its mechanotransduction.

PMID- 21177865
TI  - Kinetics comparisons of mammalian Atg4 homologues indicate selective preferences
      toward diverse Atg8 substrates.
AB  - The Atg4 cysteine proteases are required for processing Atg8 for the latter to be
      conjugated to phosphatidylethanolamine on autophagosomal membranes, a key step in
      autophagosome biogenesis. Notably, whereas there are only one atg4 and one atg8
      gene in the yeast, the mammals have four Atg4 homologues and six Atg8 homologues.
      The Atg8 homologues seem to play different roles in autophagosome biogenesis, and
      previous studies had indicated that they could be differentially processed by
      Atg4 homologues. The present study provided the first detailed kinetics analysis
      of all four Atg4 homologues against four representative Atg8 homologues. The data
      indicated that Atg4B possessed the broadest spectrum against all substrates,
      followed by Atg4A, whereas Atg4C and Atg4D had minimal activities as did the
      catalytic mutant of Atg4B (C74S). On the other hand, GATE-16 seemed to be the
      overall best substrate for Atg4 proteases. The kinetics parameters of Atg4B were
      also affected by its structure and that of the substrates, indicating a process
      of induced fit. The determination of the kinetics parameters of the various Atg4
      Atg8 pairs provides a base for the understanding of the potential selective
      impact of the reaction on autophagosome biogenesis.

PMID- 21177866
TI  - Copper promotes the trafficking of the amyloid precursor protein.
AB  - Accumulation of the amyloid beta peptide in the cortical and hippocampal regions
      of the brain is a major pathological feature of Alzheimer disease. Amyloid beta
      peptide is generated from the sequential protease cleavage of the amyloid
      precursor protein (APP). We reported previously that copper increases the level
      of APP at the cell surface. Here we report that copper, but not iron or zinc,
      promotes APP trafficking in cultured polarized epithelial cells and neuronal
      cells. In SH-SY5Y neuronal cells and primary cortical neurons, copper promoted a
      redistribution of APP from a perinuclear localization to a wider distribution,
      including neurites. Importantly, a change in APP localization was not attributed
      to an up-regulation of APP protein synthesis. Using live cell imaging and
      endocytosis assays, we found that copper promotes an increase in cell surface APP
      by increasing its exocytosis and reducing its endocytosis, respectively. This
      study identifies a novel mechanism by which copper regulates the localization and
      presumably the function of APP, which is of major significance for understanding
      the role of APP in copper homeostasis and the role of copper in Alzheimer
      disease.

PMID- 21177867
TI  - Calpain activation by Wingless-type murine mammary tumor virus integration site
      family, member 5A (Wnt5a) promotes axonal growth.
AB  - Axon development involves spatial-temporal cytoskeletal reorganization. However,
      how the cytoskeleton remodeling is modulated by extracellular cues is unclear.
      Here, we report a role of Wnt/Ca(2+) signaling in regulating actin and growth
      cone dynamics. We found that treatment of cultured cortical neurons with Wnt5a, a
      non-canonical Wnt, either globally or locally, caused an increase in the activity
      of calpain, a calcium-dependent protease responsible for the cleavage of several
      actin binding proteins, including spectrin. Treatment with Wnt5a promoted growth
      cone advance, as well as axonal growth, and these effects were prevented by
      chelating intracellular calcium, inhibition or down-regulation of calpain, or
      blockade of spectrin cleavage by competitive peptides. Interestingly, both Wnt5a
      and activated calpain were found to be mainly distributed in the axon-rich
      intermediate zone of neocortex. Down-regulating calpain expression interfered
      with the growth of callosal axons in vivo. Thus, Wnt5a serves as a physiological
      cue to stimulate localized calpain activity, which in turn promotes growth cone
      advance and axonal growth.

PMID- 21177868
TI  - N-cadherin regulates p38 MAPK signaling via association with JNK-associated
      leucine zipper protein: implications for neurodegeneration in Alzheimer disease.
AB  - Synaptic loss, which strongly correlates with the decline of cognitive function,
      is one of the pathological hallmarks of Alzheimer disease. N-cadherin is a cell
      adhesion molecule essential for synaptic contact and is involved in the
      intracellular signaling pathway at the synapse. Here we report that the
      functional disruption of N-cadherin-mediated cell contact activated p38 MAPK in
      murine primary neurons, followed by neuronal death. We further observed that
      treatment with Abeta(42) decreased cellular N-cadherin expression through NMDA
      receptors accompanied by increased phosphorylation of both p38 MAPK and Tau in
      murine primary neurons. Moreover, expression levels of phosphorylated p38 MAPK
      were negatively correlated with that of N-cadherin in human brains. Proteomic
      analysis of human brains identified a novel interaction between N-cadherin and
      JNK-associated leucine zipper protein (JLP), a scaffolding protein involved in
      the p38 MAPK signaling pathway. We demonstrated that N-cadherin expression had an
      inhibitory effect on JLP-mediated p38 MAPK signal activation by decreasing the
      interaction between JLP and p38 MAPK in COS7 cells. Also, this study demonstrated
      a novel physical and functional association between N-cadherin and p38 MAPK and
      suggested neuroprotective roles of cadherin-based synaptic contact. The
      dissociation of N-cadherin-mediated synaptic contact by Abeta may underlie the
      pathological basis of neurodegeneration such as neuronal death, synaptic loss,
      and Tau phosphorylation in Alzheimer disease brain.

PMID- 21177869
TI  - mTOR-dependent regulation of PHLPP expression controls the rapamycin sensitivity
      in cancer cells.
AB  - PHLPP belongs to a novel family of protein phosphatases that serve as negative
      regulators of Akt. There are two isoforms, PHLPP1 and PHLPP2, identified in this
      family. Our previous studies indicated a tumor suppressor role of both PHLPP
      isoforms in colon cancer. Here we report that the expression of PHLPP is
      controlled by mTOR-dependent protein translation in colon and breast cancer
      cells. Treating cells with rapamycin or knockdown of mTOR using RNAi results in a
      marked decrease of PHLPP protein expression. In contrast, stable knockdown of
      TSC2, a negative regulator of mTOR activity, increases PHLPP expression. The
      rapamycin-mediated down-regulation of PHLPP is blocked by expression of a
      rapamycin-insensitive mutant of p70S6K. In addition, depletion of 4E-BP1
      expression by RNAi results in an increase of PHLPP expression and resistance to
      rapamycin-induced down-regulation. Moreover, inhibition of mTOR activity by amino
      acid or glucose starvation reduces PHLPP expression in cells. Functionally, we
      show that rapamycin-mediated inhibition of PHLPP expression contributes to
      rapamycin resistance in colon cancer cells. Thus, our studies identify a
      compensatory feedback regulation in which the activation of Akt is inhibited by
      up-regulation of PHLPP through mTOR, and this mTOR-dependent expression of PHLPP
      subsequently determines the rapamycin sensitivity of cancer cells.

PMID- 21177870
TI  - Activation loop phosphorylation of ERK3/ERK4 by group I p21-activated kinases
      (PAKs) defines a novel PAK-ERK3/4-MAPK-activated protein kinase 5 signaling
      pathway.
AB  - Classical mitogen-activated protein (MAP) kinases are activated by dual
      phosphorylation of the Thr-Xxx-Tyr motif in their activation loop, which is
      catalyzed by members of the MAP kinase kinase family. The atypical MAP kinases
      extracellular signal-regulated kinase 3 (ERK3) and ERK4 contain a single phospho
      acceptor site in this segment and are not substrates of MAP kinase kinases.
      Previous studies have shown that ERK3 and ERK4 are phosphorylated on activation
      loop residue Ser-189/Ser-186, resulting in their catalytic activation. However,
      the identity of the protein kinase mediating this regulatory event has remained
      elusive. We have used an unbiased biochemical purification approach to isolate
      the kinase activity responsible for ERK3 Ser-189 phosphorylation. Here, we report
      the identification of group I p21-activated kinases (PAKs) as ERK3/ERK4
      activation loop kinases. We show that group I PAKs phosphorylate ERK3 and ERK4 on
      Ser-189 and Ser-186, respectively, both in vitro and in vivo, and that expression
      of activated Rac1 augments this response. Reciprocally, silencing of PAK1/2/3
      expression by RNA interference (RNAi) completely abolishes Rac1-induced Ser-189
      phosphorylation of ERK3. Importantly, we demonstrate that PAK-mediated
      phosphorylation of ERK3/ERK4 results in their enzymatic activation and in
      downstream activation of MAP kinase-activated protein kinase 5 (MK5) in vivo. Our
      results reveal that group I PAKs act as upstream activators of ERK3 and ERK4 and
      unravel a novel PAK-ERK3/ERK4-MK5 signaling pathway.

PMID- 21177871
TI  - Small molecule AKAP-protein kinase A (PKA) interaction disruptors that activate
      PKA interfere with compartmentalized cAMP signaling in cardiac myocytes.
AB  - A-kinase anchoring proteins (AKAPs) tether protein kinase A (PKA) and other
      signaling proteins to defined intracellular sites, thereby establishing
      compartmentalized cAMP signaling. AKAP-PKA interactions play key roles in various
      cellular processes, including the regulation of cardiac myocyte contractility. We
      discovered small molecules, 3,3'-diamino-4,4'-dihydroxydiphenylmethane (FMP-API
      1) and its derivatives, which inhibit AKAP-PKA interactions in vitro and in
      cultured cardiac myocytes. The molecules bind to an allosteric site of regulatory
      subunits of PKA identifying a hitherto unrecognized region that controls AKAP-PKA
      interactions. FMP-API-1 also activates PKA. The net effect of FMP-API-1 is a
      selective interference with compartmentalized cAMP signaling. In cardiac
      myocytes, FMP-API-1 reveals a novel mechanism involved in terminating beta
      adrenoreceptor-induced cAMP synthesis. In addition, FMP-API-1 leads to an
      increase in contractility of cultured rat cardiac myocytes and intact hearts.
      Thus, FMP-API-1 represents not only a novel means to study compartmentalized
      cAMP/PKA signaling but, due to its effects on cardiac myocytes and intact hearts,
      provides the basis for a new concept in the treatment of chronic heart failure.

PMID- 21177872
TI  - Asparagine and aspartate hydroxylation of the cytoskeletal ankyrin family is
      catalyzed by factor-inhibiting hypoxia-inducible factor.
AB  - Factor-inhibiting hypoxia-inducible factor (FIH) catalyzes the beta-hydroxylation
      of an asparagine residue in the C-terminal transcriptional activation domain of
      the hypoxia inducible factor (HIF), a modification that negatively regulates HIF
      transcriptional activity. FIH also catalyzes the hydroxylation of highly
      conserved Asn residues within the ubiquitous ankyrin repeat domain (ARD)
      containing proteins. Hydroxylation has been shown to stabilize localized regions
      of the ARD fold in the case of a three-repeat consensus ankyrin protein, but this
      phenomenon has not been demonstrated for the extensive naturally occurring ARDs.
      Here we report that the cytoskeletal ankyrin family are substrates for FIH
      catalyzed hydroxylations. We show that the ARD of ankyrinR is multiply
      hydroxylated by FIH both in vitro and in endogenous proteins purified from human
      and mouse erythrocytes. Hydroxylation of the D34 region of ankyrinR ARD (ankyrin
      repeats 13-24) increases its conformational stability and leads to a reduction in
      its interaction with the cytoplasmic domain of band 3 (CDB3), demonstrating the
      potential for FIH-catalyzed hydroxylation to modulate protein-protein
      interactions. Unexpectedly we found that aspartate residues in ankyrinR and
      ankyrinB are hydroxylated and that FIH-catalyzed aspartate hydroxylation also
      occurs in other naturally occurring AR sequences. The crystal structure of an FIH
      variant in complex with an Asp-substrate peptide together with NMR analyses of
      the hydroxylation product identifies the 3S regio- and stereoselectivity of the
      FIH-catalyzed Asp hydroxylation, revealing a previously unprecedented
      posttranslational modification.

PMID- 21177874
TI  - Not doing is not the opposite of doing: implications for attitudinal models of
      behavioral prediction.
AB  - This study argues for and tests the prediction that cognitions about not
      performing a behavior are not simple opposites of cognitions about performing the
      same behavior because they rely on separate goals. Three behaviors (i.e., eating
      meat, doing vigorous physical activity, and breastfeeding) are examined, for
      which performing and not performing are means to different goals. In the context
      of the theory of planned behavior, the discriminant validity of constructs
      related to performing and not performing behaviors is tested. Moreover, the
      simultaneous validities of perceived behavioral control over doing and not doing
      for the prediction of both intentions and the incremental validity of both
      intentions in predicting behavior are investigated. Results show that the
      constructs related to performing and not performing a behavior independently
      contribute to the prediction of intentions and behaviors. Implications of
      considering separable motivational systems underlying doing and not doing are
      discussed.

PMID- 21177873
TI  - Endocytic recycling proteins EHD1 and EHD2 interact with fer-1-like-5 (Fer1L5)
      and mediate myoblast fusion.
AB  - The mammalian ferlins are calcium-sensing, C2 domain-containing proteins involved
      in vesicle trafficking. Myoferlin and dysferlin regulate myoblast fusion and
      muscle membrane resealing, respectively. Correspondingly, myoferlin is most
      highly expressed in singly nucleated myoblasts, whereas dysferlin expression is
      increased in mature, multinucleated myotubes. Myoferlin also mediates endocytic
      recycling and participates in trafficking the insulin-like growth factor
      receptor. We have now characterized a novel member of the ferlin family, Fer1L5,
      because of its high homology to dysferlin and myoferlin. We found that Fer1L5
      protein is expressed in small myotubes that contain only two to four nuclei. We
      also found that Fer1L5 protein binds directly to the endocytic recycling proteins
      EHD1 and EHD2 and that the second C2 domain in Fer1L5 mediates this interaction.
      Reduction of EHD1 and/or EHD2 inhibits myoblast fusion, and EHD2 is required for
      normal translocation of Fer1L5 to the plasma membrane. The characterization of
      Fer1L5 and its interaction with EHD1 and EHD2 underscores the complex requirement
      of ferlin proteins and mediators of endocytic recycling for membrane trafficking
      events during myotube formation.

PMID- 21177875
TI  - Planning what not to eat: ironic effects of implementation intentions negating
      unhealthy habits.
AB  - The present studies tested the effectiveness of implementation intentions with an
      "if [situation], then not [habitual response]" structure. Based on ironic process
      theory and the literature on the processing of negations, it was expected that
      these "negation implementation intentions" would, ironically, strengthen the
      habit (situation-response association) one aims to break. In line with the
      hypotheses, forming negation implementation intentions resulted in cognitive
      ironic rebound effects as well as behavioral ironic rebound effects compared to
      an intention only condition or a replacement implementation intention.
      Additionally, it was found that negation implementation intentions are most
      likely to result in ironic rebound effects when the habit to be negated is
      strong. Although implementation intentions are generally highly effective in
      facilitating behavior change even when this involves breaking unwanted habits,
      the present research suggests that they are ineffective when they have a negating
      structure.

PMID- 21177876
TI  - Trait social anxiety and physiological activation: cardiovascular threat during
      social interaction.
AB  - Physiological activation is thought to be a part of the constellation of
      responses that accompany social anxiety, but evidence regarding the nature of
      such activation is mixed. In two studies, the relationship between trait social
      anxiety and responses during social interaction was explored using on-line
      cardiovascular indexes of threat. Across Studies 1 and 2, women higher in trait
      social anxiety exhibited cardiovascular responses consistent with greater threat
      during the social interaction than those lower in social anxiety. Retrospective
      self-reports (Studies 1 and 2), as well as partner ratings and interaction
      behavior (Study 2), also revealed consistent differences as a function of trait
      social anxiety. Study 2 added male participants, among whom a divergence emerged
      between results for physiological measures and other responses. These findings
      have implications for understanding physiological as well as psychological
      processes among people with social anxiety during social interaction.

PMID- 21177877
TI  - Of virtual victims and victimized virtues: differential effects of experienced
      aggression in video games on social cooperation.
AB  - Two experimental studies were used to investigate how interacting with aggressive
      virtual characters in video games affects trust and cooperation of players. Study
      1 demonstrates that experiencing virtual aggression from a victim's perspective
      can impair players' investments in a subsequent common goods dilemma situation.
      This effect is mediated by reduced expectations of trust in the cooperativeness
      of interaction partners. In Study 2 the same effect was replicated by using a
      different cooperation task and by investigating the moderating role of justice
      sensitivity from a victim's perspective as a dispositional factor. Participants
      transferred less money to an unknown partner in a trust game after exposure to
      aggressive nonplayer characters in a video game. This effect was stronger for
      people high in victim sensitivity. Results of both studies can be interpreted in
      line with the sensitivity to mean intentions model and add to the body of
      research on violent media effects.

PMID- 21177879
TI  - Rude and inappropriate: the role of self-control in following social norms.
AB  - Following social norms to avoid deviant or socially inappropriate behavior may
      require self-control. This was tested in two experiments that experimentally
      manipulated individuals' level of self-control strength. In the first experiment,
      individuals whose self-control capacity was depleted were more likely to
      misrepresent how many problems they solved and work after being told to stop
      while working on a timed test. These same results were found in individuals low
      in trait self-control. This was especially true when the certainty of getting
      caught was low. In the second experiment, depleted individuals were ruder to the
      experimenter than nondepleted participants. The results have implications for
      understanding how self-control contributes to normative behavior.

PMID- 21177878
TI  - Misery has more company than people think: underestimating the prevalence of
      others' negative emotions.
AB  - Four studies document underestimations of the prevalence of others' negative
      emotions and suggest causes and correlates of these erroneous perceptions. In
      Study 1a, participants reported that their negative emotions were more private or
      hidden than were their positive emotions; in Study 1b, participants
      underestimated the peer prevalence of common negative, but not positive,
      experiences described in Study 1a. In Study 2, people underestimated negative
      emotions and overestimated positive emotions even for well-known peers, and this
      effect was partially mediated by the degree to which those peers reported
      suppression of negative (vs. positive) emotions. Study 3 showed that lower
      estimations of the prevalence of negative emotional experiences predicted greater
      loneliness and rumination and lower life satisfaction and that higher estimations
      for positive emotional experiences predicted lower life satisfaction. Taken
      together, these studies suggest that people may think they are more alone in
      their emotional difficulties than they really are.

PMID- 21177880
TI  - The aminoglycoside resistance methyltransferases from the ArmA/Rmt family operate
      late in the 30S ribosomal biogenesis pathway.
AB  - Bacterial resistance to 4,6-type aminoglycoside antibiotics, which target the
      ribosome, has been traced to the ArmA/RmtA family of rRNA methyltransferases.
      These plasmid-encoded enzymes transfer a methyl group from S-adenosyl-L
      methionine to N7 of the buried G1405 in the aminoglycoside binding site of 16S
      rRNA of the 30S ribosomal subunit. ArmA methylates mature 30S subunits but not
      16S rRNA, 50S, or 70S ribosomal subunits or isolated Helix 44 of the 30S subunit.
      To more fully characterize this family of enzymes, we have investigated the
      substrate requirements of ArmA and to a lesser extent its ortholog RmtA. We
      determined the Mg+2 dependence of ArmA activity toward the 30S ribosomal subunits
      and found that the enzyme recognizes both low Mg+2 (translationally inactive) and
      high Mg+2 (translationally active) forms of this substrate. We tested the effects
      of LiCl pretreatment of the 30S subunits, initiation factor 3 (IF3), and
      gentamicin/kasugamycin resistance methyltransferase (KsgA) on ArmA activity and
      determined whether in vivo derived pre-30S ribosomal subunits are ArmA
      methylation substrates. ArmA failed to methylate the 30S subunits generated from
      LiCl washes above 0.75 M, despite the apparent retention of ribosomal proteins
      and a fully mature 16S rRNA. From our experiments, we conclude that ArmA is most
      active toward the 30S ribosomal subunits that are at or very near full maturity,
      but that it can also recognize more than one form of the 30S subunit.

PMID- 21177881
TI  - Widespread regulatory activity of vertebrate microRNA* species.
AB  - An obligate intermediate during microRNA (miRNA) biogenesis is an ~22-nucleotide
      RNA duplex, from which the mature miRNA is preferentially incorporated into a
      silencing complex. Its partner miRNA* species is generally regarded as a
      passenger RNA, whose regulatory capacity has not been systematically examined in
      vertebrates. Our bioinformatic analyses demonstrate that a substantial fraction
      of miRNA* species are stringently conserved over vertebrate evolution,
      collectively exhibit greatest conservation in their seed regions, and define
      complementary motifs whose conservation across vertebrate 3'-UTR evolution is
      statistically significant. Functional tests of 22 miRNA expression constructs
      revealed that a majority could repress both miRNA and miRNA* perfect match
      reporters, and the ratio of miRNA:miRNA* sensor repression was correlated with
      the endogenous ratio of miRNA:miRNA* reads. Analysis of microarray data provided
      transcriptome-wide evidence for the regulation of seed-matched targets for both
      mature and star strand species of several miRNAs relevant to oncogenesis,
      including mir-17, mir-34a, and mir-19. Finally, 3'-UTR sensor assays and
      mutagenesis tests confirmed direct repression of five miR-19* targets via star
      seed sites. Overall, our data demonstrate that miRNA* species have demonstrable
      impact on vertebrate regulatory networks and should be taken into account in
      studies of miRNA functions and their contribution to disease states.

PMID- 21177882
TI  - Use of central venous oxygen saturation to guide therapy.
AB  - The use of pulmonary artery catheters has diminished, so that other technologies
      are emerging. Central venous oxygen saturation measurement (ScvO2) as a surrogate
      for mixed venous oxygen saturation measurement (SvO2) is simple and clinically
      accessible. To maximize the clinical utility of ScvO2 (or SvO2) measurement, it
      is useful to review what the measurement means in a physiologic context,how the
      measurement is made, important limitations, and how this measurement may be
      helpful in common clinical scenarios. Compared with cardiac output measurement,
      SvO2 is more directly related to tissue oxygenation. Furthermore,when tissue
      oxygenation is a clinical concern, SvO2 is less prone to error compared with
      cardiac output, where small measurement errors may lead to larger errors in
      interpreting adequacy of oxygen delivery. ScvO2 should be measured from the tip
      of a central venous catheter placed close to, or within, the right atrium to
      reduce measurement error. Correct clinical interpretation of SvO2, or its
      properly measured ScvO2 surrogate, can be used to (1) estimate cardiac output
      using the Fick equation, (2) better understand whether a patient's oxygen
      delivery is adequate to meet their oxygen demands, (3) help guide clinical
      practice, particularly when resuscitating patients using validated early goal
      directed therapy treatment protocols, (4) understand and treat arterial
      hypoxemia, and (5) rapidly estimate shunt fraction (venous admixture).

PMID- 21177883
TI  - Lung cancer in chronic obstructive pulmonary disease: enhancing surgical options
      and outcomes.
AB  - Patients with chronic obstructive pulmonary disease (COPD) are at increased risk
      for both the development of primary lung cancer, as well as poor outcome after
      lung cancer diagnosis and treatment. Because of existing impairments in lung
      function, patients with COPD often do not meet traditional criteria for tolerance
      of definitive surgical lung cancer therapy. Emerging information regarding the
      physiology of lung resection in COPD indicates that postoperative decrements in
      lung function may be less than anticipated by traditional prediction tools. In
      patients with COPD, more inclusive consideration for surgical resection with
      curative intent may be appropriate as limited surgical resections or nonsurgical
      therapeutic options provide inferior survival. Furthermore, optimizing
      perioperative COPD medical care according to clinical practice guidelines
      including smoking cessation can potentially minimize morbidity and improve
      functional status in this often severely impaired patient population.

PMID- 21177884
TI  - Novel developments in the epidemic of human immunodeficiency virus and
      tuberculosis coinfection.
AB  - Tuberculosis (TB) disease remains one of the highest causes of mortality in HIV
      infected individuals, and HIV-TB coinfection continues to grow at alarming rates,
      especially in sub-Saharan Africa. Surprisingly, a number of important areas
      regarding coinfection remain unclear. For example, increased risk of TB disease
      begins early in the course of HIV infection; however, the mechanism by which HIV
      increases this risk is not well understood. In addition, there is lack of
      consensus on the optimal way to diagnose latent TB infection and to manage active
      disease in those who are HIV infected. Furthermore, effective point-of-care
      testing for TB disease remains elusive. This review discusses key areas in the
      epidemiology, pathogenesis, diagnosis, and management of active and latent TB in
      those infected with HIV, focusing attention on issues related to high- and low
      burden areas. Particular emphasis is placed on controversial areas where there
      are gaps in knowledge and on future directions of study.

PMID- 21177885
TI  - Hypoxia enhances platelet-derived growth factor signaling in the pulmonary
      vasculature by down-regulation of protein tyrosine phosphatases.
AB  - RATIONALE: Platelet-derived growth factor (PDGF) plays a pivotal role in the
      pathobiology of pulmonary hypertension (PH) because it promotes pulmonary
      vascular remodeling. PH is frequently associated with pulmonary hypoxia.
      OBJECTIVES: To investigate whether hypoxia alters PDGF beta receptor (betaPDGFR)
      signaling in the pulmonary vasculature. METHODS: The impact of chronic hypoxia on
      signal transduction by the betaPDGFR was measured in human pulmonary arterial
      smooth muscle cells (hPASMC) in vitro, and in mice with hypoxia-induced PH in
      vivo. MEASUREMENTS AND MAIN RESULTS: Chronic hypoxia significantly enhanced PDGF
      BB-dependent proliferation and chemotaxis of hPASMC. Pharmacologic inhibition of
      PI3 kinase (PI3K) and PLCgamma abrogated these events under both normoxia and
      hypoxia. Although hypoxia did not affect betaPDGFR expression, it increased the
      ligand-induced tyrosine phosphorylation of the receptor, particularly at binding
      sites for PI3K (Y751) and PLCgamma (Y1021). The activated betaPDGFR is
      dephosphorylated by protein tyrosine phosphatases (PTPs). Interestingly, hypoxia
      decreased expression of numerous PTPs (T cell PTP, density-enhanced phosphatase
      1, PTP1B, and SH2 domain-containing phosphatase-2), resulting in reduced PTP
      activity. Hypoxia-inducible factor (HIF)-1alpha is involved in this regulation of
      gene expression, because hypoxia-induced betaPDGFR hyperphosphorylation and PTP
      down-regulation were abolished by HIF-1alpha siRNA and by the HIF-1alpha
      inhibitor 2-methoxyestradiol. betaPDGFR hyperphosphorylation and PTP down
      regulation were also present in vivo in mice with chronic hypoxia-induced PH.
      CONCLUSIONS: Hypoxia reduces expression and activity of betaPDGFR-antagonizing
      PTPs in a HIF-1alpha-dependent manner, thereby enhancing receptor activation and
      proliferation and chemotaxis of hPASMC. Because hyperphosphorylation of the
      betaPDGFR and down-regulation of PTPs occur in vivo, this mechanism likely has
      significant impact on the development and progression of PH and other hypoxia
      associated diseases.

PMID- 21177887
TI  - Identification of Pseudallescheria and Scedosporium species by three molecular
      methods.
AB  - The major clinically relevant species in Scedosporium (teleomorph
      Pseudallescheria) are Pseudallescheria boydii, Scedosporium aurantiacum,
      Scedosporium apiospermum, and Scedosporium prolificans, while Pseudallescheria
      minutispora, Petriellopsis desertorum, and Scedosporium dehoogii are exceptional
      agents of disease. Three molecular methods targeting the partial beta-tubulin
      gene were developed and evaluated to identify six closely related species of the
      S. apiospermum complex using quantitative real-time PCR (qPCR), PCR-based reverse
      line blot (PCR-RLB), and loop-mediated isothermal amplification (LAMP). qPCR was
      not specific enough for the identification of all species but had the highest
      sensitivity. The PCR-RLB assay was efficient for the identification of five
      species. LAMP distinguished all six species unambiguously. The analytical
      sensitivities of qPCR, PCR-RLB, and LAMP combined with MagNAPure, CTAB
      (cetyltrimethylammonium bromide), and FTA filter (Whatman) extraction were 50, 5
      * 10(3), and 5 * 10(2) cells/MUl, respectively. When LAMP was combined with a
      simplified DNA extraction method using an FTA filter, identification to the
      species level was achieved within 2 h, including DNA extraction. The FTA-LAMP
      assay is therefore recommended as a cost-effective, simple, and rapid method for
      the identification of Scedosporium species.

PMID- 21177888
TI  - Comparison of Salmonella enterica serovar Heidelberg isolates from human patients
      with those from animal and food sources.
AB  - Seventy-eight Salmonella enterica serovar Heidelberg isolates from humans were
      tested for antimicrobial susceptibility, resistance genes, and plasmids and
      genotyped by pulsed-field gel electrophoresis (PFGE). Most (88%) contained
      plasmids, and 47% were resistant to antimicrobials. The overall results were
      compared to those of previous S. Heidelberg studies of food- and animal-related
      sources, and multiple similarities were observed.

PMID- 21177889
TI  - Clonal diversity of nosocomial epidemic Acinetobacter baumannii strains isolated
      in Spain.
AB  - Acinetobacter baumannii is one of the major pathogens involved in nosocomial
      outbreaks. The clonal diversity of 729 epidemic strains isolated from 19 Spanish
      hospitals (mainly from intensive care units) was analyzed over an 11-year period.
      Pulsed-field gel electrophoresis (PFGE) identified 58 PFGE types that were
      subjected to susceptibility testing, rpoB gene sequencing, and multilocus
      sequence typing (MLST). All PFGE types were multidrug resistant; colistin was the
      only agent to which all pathogens were susceptible. The 58 PFGE types were
      grouped into 16 clones based on their genetic similarity (cutoff of 80%). These
      clones were distributed into one major cluster (cluster D), three medium clusters
      (clusters A, B, and C), and three minor clusters (clusters E, F, and G). The rpoB
      gene sequencing and MLST results reflected a clonal distribution, in agreement
      with the PFGE results. The MLST sequence types (STs) (and their percent
      distributions) were as follows: ST-2 (47.5%), ST-3 (5.1%), ST-15 (1.7%), ST-32
      (1.7%), ST-79 (13.6%), ST-80 (20.3%), and ST-81 (10.2%). ST-79, ST-80, and ST-81
      and the alleles cpn60-26 and recA29 are described for the first time.
      International clones I, II, and III were represented by ST-81, ST-2, and ST-3,
      respectively. ST-79 and ST-80 could be novel emerging clones. This work confirms
      PFGE and MLST to be complementary tools in clonality studies. Here PFGE was able
      to demonstrate the monoclonal pattern of most outbreaks, the inter- and
      intrahospital transmission of bacteria, and their endemic persistence in some
      wards. MLST allowed the temporal evolution and spatial distribution of Spanish
      clones to be monitored and permitted international comparisons to be made.

PMID- 21177886
TI  - Distinct host species correlate with Anaplasma phagocytophilum ankA gene
      clusters.
AB  - Anaplasma phagocytophilum is a gram-negative, tick-transmitted, obligate
      intracellular bacterium that elicits acute febrile diseases in humans and
      domestic animals. In contrast to the United States, human granulocytic
      anaplasmosis seems to be a rare disease in Europe despite the initial recognition
      of A. phagocytophilum as the causative agent of tick-borne fever in European
      sheep and cattle. Considerable strain variation has been suggested to occur
      within this species, because isolates from humans and animals differed in their
      pathogenicity for heterologous hosts. In order to explain host preference and
      epidemiological diversity, molecular characterization of A. phagocytophilum
      strains has been undertaken. Most often the 16S rRNA gene was used, but it might
      be not informative enough to delineate distinct genotypes of A. phagocytophilum.
      Previously, we have shown that A. phagocytophilum strains infecting Ixodes
      ricinus ticks are highly diverse in their ankA genes. Therefore, we sequenced the
      16S rRNA and ankA genes of 194 A. phagocytophilum strains from humans and several
      animal species. Whereas the phylogenetic analysis using 16S rRNA gene sequences
      was not meaningful, we showed that distinct host species correlate with A.
      phagocytophilum ankA gene clusters.

PMID- 21177890
TI  - Emergence of a novel Shigella flexneri serotype 4s strain that evolved from a
      serotype X variant in China.
AB  - This paper describes the first isolation of a new Shigella flexneri serotype,
      designated 4s, in Beijing, China. Genotypic and phenotypic profiling suggests
      that this isolate is a clone of the S. flexneri serotype X variant reference
      strain. Of particular concern is the multidrug resistance exhibited by this
      isolate.

PMID- 21177891
TI  - High frequency of repeated infections due to emerging genotypes of human
      respiratory syncytial viruses among children during eight successive epidemic
      seasons in Japan.
AB  - In eight successive seasons (2001 to 2009), a total of 726 human respiratory
      syncytial virus (HRSV) infections from a total of 1,560 children with acute lower
      respiratory tract illness were identified. Molecular analysis of the attachment
      (G) protein gene confirmed that 52 (7.8%) children were infected more than once
      with any of the 3 genotypes of HRSV-A (genotypes GA5, NA1, and NA2) and/or 6
      genotypes of HRSV-B (genotypes BA4, BA5, and BA7 to BA10). Repeated infections in
      46 cases (82.1%) occurred in the next season, and only one case occurred in the
      same season (10-day interval). First infections were 33 (63.5%) HRSV-A cases and
      19 (36.5%) HRSV-B cases, whereas second infections occurred in 35 (67.3%) HRSV-A
      cases and 17 (32.7%) HRSV-B cases. Third infections were attributed to 4 (100.0%)
      HRSV-A cases. Homologous subgroup reinfections were detected in 28 cases, 23 HRSV
      A cases and 5 HRSV-B cases (P = 0.005), whereas homologous genotype reinfections
      were detected only for 5 HRSV-A cases (2GA5 and 3NA2) but not any HRSV-B case.
      Heterologous subgroup reinfections were detected in 28 cases, 12 cases from HRSV
      A-to-HRSV-B reinfections and 16 cases from HRSV-B-to-HRSV-A reinfections.
      Genotypes NA1 and NA2 had higher numbers of heterologous genotype infections than
      did other genotypes. Our observations suggest that repeated infections occur more
      frequently in HRSV-A strains than in HRSV-B strains, and heterologous genotype
      reinfections occur more frequently than homologous genotype reinfections,
      especially in the case of the emerging genotypes NA1 and NA2 of HRSV-A strains
      that circulated in the community during our study period.

PMID- 21177893
TI  - Detection of fluoroquinolone-resistant organisms from rectal swabs by use of
      selective media prior to a transrectal prostate biopsy.
AB  - Sepsis caused by fluoroquinolone-resistant Escherichia coli is a risk for
      patients undergoing an ultrasound-guided, transrectal prostate biopsy. A method
      incorporating selective broth and media was evaluated using rectal swabs obtained
      from 136 patients prior to a biopsy procedure. Fluoroquinolone-resistant
      organisms were isolated from 22% of the patients included in this study.

PMID- 21177892
TI  - Host factors and portal of entry outweigh bacterial determinants to predict the
      severity of Escherichia coli bacteremia.
AB  - Escherichia coli ranks among the organisms most frequently isolated from cases of
      bacteremia. The relative contribution of the host and bacteria to E. coli
      bacteremia severity remains unknown. We conducted a prospective multicenter
      cohort study to identify host and bacterial factors associated with E. coli
      bacteremia severity. The primary endpoint was in-hospital death, up to 28 days
      after the first positive blood culture. Among 1,051 patients included, 136
      (12.9%) died. Overall, 604 (57.5%) patients were female. The median age was 70
      years, and 202 (19.2%) episodes were nosocomial. The most frequent comorbidities
      were immunocompromised status (37.9%), tobacco addiction (21.5%), and diabetes
      mellitus (20.1%). The most common portal of entry was the urinary tract (56.9%).
      Most E. coli isolates belonged to phylogenetic group B2 (52.0%). The multivariate
      analysis retained the following factors as predictive of death: older age (odds
      ratio [OR] = 1.25 [95% confidence interval {CI}, 1.09 to 1.43] for each 10-year
      increment), cirrhosis (OR = 4.85 [95% CI, 2.49 to 9.45]), hospitalization before
      bacteremia (OR = 4.13 [95% CI, 2.49 to 6.82]), being an immunocompromised patient
      not hospitalized before bacteremia (OR = 3.73 [95% CI, 2.25 to 6.18]), and a
      cutaneous portal of entry (OR = 6.45 [95% CI, 1.68 to 24.79]); a urinary tract
      portal of entry and the presence of the ireA virulence gene were negatively
      correlated with death (OR = 0.46 [95% CI, 0.30 to 0.70] and OR = 0.53 [95% CI,
      0.30 to 0.91], respectively). In summary, host factors and the portal of entry
      outweigh bacterial determinants for predicting E. coli bacteremia severity.

PMID- 21177894
TI  - Efficient differentiation of Mycobacterium abscessus complex isolates to the
      species level by a novel PCR-based variable-number tandem-repeat assay.
AB  - A novel duplex PCR method based on variable-number tandem-repeat targets to
      discriminate among Mycobacterium abscessus complex isolates was developed and
      evaluated in 85 clinical isolates. The assay accuracy was confirmed by a multiple
      target sequence analysis. The duplex PCR assay is a one-step, reliable, and
      accurate assay for discriminating M. abscessus species.

PMID- 21177895
TI  - Rifampin stability in 7H9 broth and Lowenstein-Jensen medium.
AB  - The objectives of this study were to monitor the stability of rifampin (RIF) in
      Lowenstein-Jensen medium (L-J medium) and 7H9 broth, which are the media commonly
      used for drug susceptibility testing (DST) of Mycobacterium tuberculosis.
      Rifampin degradation in stock solution, 7H9 broth, and L-J medium and during the
      inspissation process for L-J medium preparation was serially monitored by high
      performance liquid chromatography (HPLC). L-J medium-based DST was conducted to
      examine the effect of L-J medium storage on the DST outcome. The RIF stock
      solution was stable for at least 3 months when kept at either 4 degrees C or -20
      degrees C; RIF in 7H9 broth and L-J medium was almost 50% decayed after 1 week of
      storage at 37 degrees C, and rifampin could not be detected in 7H9 or L-J medium
      after 3 weeks or 6 weeks of storage at 37 degrees C. Approximately half of the
      drug was decomposed after 4 months of storage at 4 degrees C for both media, and
      after 6 months of storage at 4 degrees C, RIF in L-J medium was undetectable,
      while 38% of RIF remained in 7H9 medium. Approximately 21, 24, 29, and 35% RIF
      degradations were detected when the L-J medium was coagulated at 75 degrees C, 80
      degrees C, 85 degrees C, and 90 degrees C, respectively. The DST outcomes when
      using L-J medium stored for different periods of time were consistent with the
      RIF concentration monitoring data. Rifampin in stock solution is stable for at
      least 3 months at a reduced storage temperature. Media containing RIF should be
      prepared strictly according to validated standard operating procedures. RIF
      degradation is a possible reason for false resistance categorizations of M.
      tuberculosis isolates in the clinical laboratory.

PMID- 21177896
TI  - Clostridium difficile colonization in early infancy is accompanied by changes in
      intestinal microbiota composition.
AB  - Clostridium difficile is a major enteric pathogen responsible for antibiotic
      associated diarrhea. Host susceptibility to C. difficile infections results
      partly from inability of the intestinal microbiota to resist C. difficile
      colonization. During early infancy, asymptomatic colonization by C. difficile is
      common and the intestinal microbiota shows low complexity. Thus, we investigated
      the potential relationship between the microbiota composition and the
      implantation of C. difficile in infant gut. Fecal samples from 53 infants, ages 0
      to 13 months, 27 negative and 26 positive for C. difficile, were studied.
      Dominant microbiota profiles were assessed by PCR-temporal temperature gradient
      gel electrophoresis (TTGE). Bacterial signatures of the intestinal microbiota
      associated with colonization by C. difficile were deciphered using principal
      component analysis (PCA). Resulting bands of interest in TTGE profiles were
      excised, sequenced, and analyzed by nucleotide BLAST (NCBI). While global
      biodiversity was not affected, interclass PCA on instrumental variables
      highlighted significant differences in dominant bacterial species between C.
      difficile-colonized and noncolonized infants (P = 0.017). Four bands were
      specifically associated with the presence or absence of C. difficile: 16S rRNA
      gene sequences related to Ruminococcus gnavus and Klebsiella pneumoniae for
      colonized infants and to Bifidobacterium longum for noncolonized infants. We
      demonstrated that the presence of C. difficile in the intestinal microbiota of
      infants was associated with changes in this ecosystem's composition. These
      results suggest that the composition of the gut microbiota might be crucial in
      the colonization process, although the chronology of events remains to be
      determined.

PMID- 21177897
TI  - Development and evaluation of a real-time PCR assay for detection and
      quantification of blastocystis parasites in human stool samples: prospective
      study of patients with hematological malignancies.
AB  - Blastocystis anaerobic parasites are widespread worldwide in the digestive tract
      of many animal species, including humans. Epidemiological Blastocystis studies
      are often limited by the poor sensitivity of standard parasitological assays for
      its detection. This report presents a highly sensitive real-time quantitative PCR
      (qPCR) assay developed to detect Blastocystis parasites in stool samples. The
      assay targets a partial sequence of the Blastocystis small ribosomal subunit
      (SSU) rRNA gene, allowing subtyping (ST) of Blastocystis isolates by direct
      sequencing of qPCR products. This qPCR method was assessed in a prospective study
      of 186 patients belonging to two cohorts--a group of 94 immunocompromised
      patients presenting hematological malignancies and a control group of 92
      nonimmunocompromised patients. Direct-light microscopy and xenic in vitro stool
      culture analysis showed only 29% and 52% sensitivity, respectively, compared to
      our qPCR assay. Of the 27 (14.5%) Blastocystis-positive patients, 8 (4%)
      experienced digestive symptoms. No correlation was found between symptomatic
      patients and immune status, parasite load, or parasite subtypes, although
      subtyping of all isolates revealed a high (63.0%) prevalence of ST4. Two
      unexpected avian subtypes were found, i.e., ST6 and ST7, which are frequently
      isolated in Asia but rarely present in Western countries. In conclusion, this
      qPCR proved by far the most sensitive of the tested methods and allowed subtype
      determination by direct sequencing of qPCR products. New diagnostic tools such as
      the qPCR are essential for evaluating the clinical relevance of Blastocystis
      subtypes and their role in acute or chronic digestive disorders.

PMID- 21177898
TI  - Characteristics of Cryptosporidium transmission in preweaned dairy cattle in
      Henan, China.
AB  - To estimate the prevalence and public health significance of cryptosporidiosis in
      preweaned calves in China, 801 fecal samples from eight farms in seven areas in
      Henan Province were examined for Cryptosporidium oocysts. The overall infection
      rate of Cryptosporidium was 21.5%, with the farm in Xinxiang having the highest
      prevalence (40%). No significant difference in infection rates was observed
      between seasons. Cryptosporidium spp. were characterized by PCR-restriction
      fragment length polymorphism (RFLP) analysis of the small subunit (SSU) rRNA gene
      and DNA sequencing of the 60-kDa glycoprotein (gp60) gene. The SSU rRNA-based PCR
      identified four Cryptosporidium species, including Cryptosporidium parvum
      (54/172), C. bovis (65/172), C. ryanae (19/172), and C. andersoni (12/172), and
      the occurrence of infections with mixed species (22/172). The earliest detection
      of C. bovis was in calves of 1 week of age, showing that the prepatent period was
      shorter than the previously stated 10 to 12 days. Infections with C. parvum
      peaked in summer, whereas C. bovis dominated in autumn and winter. There was no
      apparent difference in the age of cattle infected with either C. parvum or C.
      bovis. Sequencing analysis of the gp60 gene showed all 67 C. parvum samples
      belonged to subtype IIdA19G1. These findings suggested that the transmission of
      Cryptosporidium spp. in preweaned calves in Henan, China, appeared to be
      different from other areas both at genotype and subtype levels. Further molecular
      epidemiologic studies (including samples from both calves and humans) are needed
      to elucidate the transmission dynamics and public significance of C. parvum in
      cattle in China.

PMID- 21177899
TI  - Role of the clinical mycobacteriology laboratory in diagnosis and management of
      tuberculosis in low-prevalence settings.
AB  - Tuberculosis (TB) remains a global epidemic, despite a significant decline in
      reported cases in the United States between 2008 and 2009. While the exact nature
      of this decline is unclear, one thing remains certain: TB, including multidrug
      resistant (MDR) and extensively drug-resistant (XDR) TB, is no longer restricted
      to developing regions of the globe. It is of vital importance that both public
      and private mycobacteriology laboratories maintain the ability to detect and
      identify Mycobacterium tuberculosis from patient specimens, as well as correctly
      determine the presence of antibiotic resistance. To do this effectively requires
      careful attention to preanalytical, analytical, and postanalytical aspects of
      testing. Respiratory specimens require digestion and concentration followed by
      fluorescence microscopy. The Centers for Disease Control and Prevention (CDC)
      recommends the performance of a direct nucleic acid amplification method,
      regardless of smear results, on specimens from patients in whom the suspicion of
      tuberculosis is high. Liquid-based technologies are more rapid and sensitive for
      the detection of M. tuberculosis in culture and nucleic acid probes, but
      biochemicals are preferred for identification once growth is detected.
      Susceptibility testing is most often done using either the agar proportion method
      or a commercial broth system. New genotypic and phenotypic methods of
      susceptibility testing include first- and second-line agents and are promising,
      though not yet widely available. Finally, gamma interferon release assays are
      preferred to the tuberculin skin test for screening certain at-risk populations,
      and new CDC guidelines are available that assist clinicians in their use.

PMID- 21177900
TI  - Imipenem-resistant Nocardia cyriacigeorgica infection in a child with chronic
      granulomatous disease.
AB  - Nocardia spp. can lead to local or disseminated infections, especially in
      immunocompromised patients. Combination therapy of amikacin and imipenem is
      commonly used to treat severe nocardial infections. We describe a patient with
      imipenem-resistant Nocardia cyriacigeorgica, which, to our knowledge, has not
      been previously reported among isolates of this species.

PMID- 21177901
TI  - Evaluation of the Cobas TaqMan MTB test for direct detection of Mycobacterium
      tuberculosis complex in respiratory specimens.
AB  - The Cobas TaqMan MTB test, based on real-time PCR technology, was evaluated for
      direct detection of Mycobacterium tuberculosis complex (MTBC) in respiratory
      specimens. A total of 1,093 samples from 446 patients, including 118 acid-fast
      smear-positive and 975 acid-fast smear-negative specimens, were investigated.
      Diagnostic cultures performed with 7H11 agar, Lowenstein-Jensen medium, and the
      Bactec MGIT 960 system were considered the reference methods. When discrepant
      results between the Cobas TaqMan MTB test and culture occurred, additional
      results from the BD MGIT TBc identification test and the GenoType Mycobacterium
      CM test performed on growth-positive and acid-fast-stain-positive MGIT tubes and
      review of the patient's medical history were used for discrepancy analysis. The
      overall sensitivity, specificity, positive predictive value, and negative
      predictive value for the Cobas TaqMan MTB test were 91.5%, 98.7%, 91.5%, and
      98.7%, respectively. In general, the performance of the new Cobas TaqMan MTB test
      was comparable to that of the replaced Cobas Amplicor MTB system. The most
      prominent feature of the new system was its extraordinarily high sensitivity
      (79.5%) for detecting MTBC in smear-negative specimens; out of 44 smear-negative
      but culture-positive specimens, 35 were positive by the new system. The Cobas
      TaqMan MTB assay, including DNA extraction, can be completed within 3 h.

PMID- 21177902
TI  - Shiga toxin-producing Escherichia coli in children: diagnosis and clinical
      manifestations of O157:H7 and non-O157:H7 infection.
AB  - Shiga toxin-producing Escherichia coli (STEC), a cause of food-borne colitis and
      hemolytic-uremic syndrome in children, can be serotype O157:H7 (O157) or other
      serotypes (non-O157). E. coli O157 can be detected by culture with sorbitol
      MacConkey agar (SMAC), but non-O157 STEC cannot be detected with this medium.
      Both O157 and non-O157 STEC can be detected by immunoassay for Shiga toxins 1 and
      2. The objectives of this study were first to compare the diagnostic utility of
      SMAC to that of the Premier EHEC enzyme immunoassay (Meridian Diagnostics) for
      detection of STEC in children and second to compare the clinical and laboratory
      characteristics of children with serotype O157:H7 STEC and non-O157:H7 STEC
      infections. Stool samples submitted for testing for STEC between April 2004 and
      September 2009 were tested by both SMAC culture and the Premier EHEC assay at
      Children's Hospital Boston. Samples positive by either test were sent for
      confirmatory testing and serotyping at the Hinton State Laboratory Institute
      (HSLI). Chart review was performed on children with confirmed STEC infection. Of
      5,110 children tested for STEC, 50 (0.9%) had STEC infection confirmed by
      culture; 33 were O157:H7 and 17 were non-O157:H7. The Premier EHEC assay and SMAC
      culture detected 96.0% and 58.0% of culture-confirmed STEC isolates (any
      serotype), respectively, and 93.9% and 87.9% of STEC O157:H7 isolates,
      respectively. There were no significant differences in disease severity or
      laboratory manifestations of STEC infection between children with O157:H7 and
      those with non-O157 STEC. The Premier EHEC assay was significantly more sensitive
      than SMAC culture for diagnosis of STEC, and O157:H7 and non-O157:H7 STEC caused
      infections of similar severity in children.

PMID- 21177903
TI  - Evaluation of the 3M rapid detection test for respiratory syncytial virus (RSV)
      in children during the early stages of the 2009 RSV season.
AB  - We report the results of the 3M rapid detection respiratory syncytial virus (RSV)
      assay. This study includes pediatric patient results from nasopharyngeal swabs
      submitted from October to December 2009. There was a sensitivity of 74% and
      specificity approaching 100% compared to the PCR-based xTAG respiratory viral
      panel.

PMID- 21177904
TI  - Detection and differentiation of Cryptosporidium spp. in human clinical samples
      by use of real-time PCR.
AB  - Real-time PCR has the potential to streamline detection and identification of
      Cryptosporidium spp. in human clinical samples. In the present article, we report
      the first such assay to allow not only detection and differentiation of the most
      common human pathogens, Cryptosporidium hominis and Cryptosporidium parvum, but
      also simultaneous amplification of a region of the small subunit (SSU) rRNA gene,
      permitting direct sequence analysis to identify any Cryptosporidium species. An
      internal control is incorporated to identify the presence of PCR inhibitors.
      Analytical sensitivity was determined to be as low as 200 oocysts per gram of
      feces processed, equivalent to 2 oocysts per PCR. The C. hominis and C. parvum
      PCRs specifically detected only species/genotypes in their respective target
      clades. Diagnostic sensitivity and specificity, evaluated against a widely used
      conventional nested SSU rRNA gene PCR as a nominated gold standard using a panel
      of 258 (151 positive and 107 negative) samples, were 100% and 99.1%,
      respectively. The assay agreed with PCR-restriction fragment length polymorphism
      analysis of the Cryptosporidium oocyst wall protein gene for 134 of 136 (98.5%)
      samples tested prospectively and typed two additional isolates. The real-time PCR
      assay was sensitive, specific, and reproducible and significantly improved
      laboratory work flow and turnaround times.

PMID- 21177905
TI  - Novel pan-genomic analysis approach in target selection for multiplex PCR
      identification and detection of Burkholderia pseudomallei, Burkholderia
      thailandensis, and Burkholderia cepacia complex species: a proof-of-concept
      study.
AB  - Burkholderia pseudomallei, Burkholderia thailandensis, and the Burkholderia
      cepacia complex differ greatly in pathogenicity and epidemiology. Yet, they are
      occasionally misidentified by biochemical profiling, and even 16S rRNA gene
      sequencing may not offer adequate discrimination between certain species groups.
      Using the 23 B. pseudomallei, four B. thailandensis, and 16 B. cepacia complex
      genome sequences available, we identified gene targets specific to each of them
      (a Tat domain protein, a 70-kDa protein, and a 12-kDa protein for B.
      pseudomallei, B. thailandensis, and the B. cepacia complex, respectively), with
      an in-house developed algorithm. Using these targets, we designed a robust
      multiplex PCR assay useful for their identification and detection from soil and
      simulated sputum samples. For all 43 B. pseudomallei, seven B. thailandensis, and
      20 B. cepacia complex (B. multivorans, n = 6; B. cenocepacia, n = 3; B. cepacia,
      n = 4; B. arboris, n = 2; B. contaminans, B. anthina, and B. pyrrocinia, n = 1
      each; other unnamed members, n = 2) isolates, the assay produced specific
      products of predicted size without false positives or negatives. Of the 60 soil
      samples screened, 19 (31.6%) and 29 (48.3%) were positive for B. pseudomallei and
      the B. cepacia complex, respectively, and in four (6.7%) soil samples, the
      organisms were codetected. DNA sequencing confirmed that all PCR products
      originated from their targeted loci. This novel pan-genomic analysis approach in
      target selection is simple, computationally efficient, and potentially applicable
      to any species that harbors species-specific genes. A multiplex PCR assay for
      rapid and accurate identification and detection of B. pseudomallei, B.
      thailandensis, and the B. cepacia complex was developed and verified.

PMID- 21177906
TI  - Overestimation of incidence of hepatitis B virus mixed-genotype infections by use
      of the new line probe INNO-LiPA genotyping assay.
AB  - The new version of the INNO-LiPA HBV genotyping assay (Innogenetics) developed to
      identify all hepatitis B virus (HBV) genotypes, A to H, has been evaluated in
      comparison with sequencing of PCR-amplified HBV DNA from 200 samples before or
      after cloning. The genotyping data obtained with INNO-LiPA were in agreement with
      those from direct sequencing in the 179 samples characterized by the two methods.
      INNO-LiPA revealed 28 mixed infections. However, sequencing after molecular
      cloning confirmed only 15 of them and did not identify any that were of genotype
      H (n = 9). Our study demonstrates that INNO-LiPA overestimates mixed infections
      as a result of erroneous genotype H detection.

PMID- 21177907
TI  - Development and evaluation of a reverse transcription-loop-mediated isothermal
      amplification assay for rapid detection of enterovirus 71.
AB  - Human enterovirus 71 (EV71) is the major etiological agent of hand, foot, and
      mouth disease (HFMD), which is a common infectious disease in young children and
      infants. EV71 can cause various clinical manifestations and has been associated
      with severe neurological complications; it has resulted in fatalities during
      recent outbreaks in Asian-Pacific regions since 1997. The early and rapid
      detection is critical for prevention and control of EV71 infection, since no
      vaccine or antiviral drugs are currently available. In this study, a simple and
      sensitive reverse transcription-loop-mediated isothermal amplification (RT-LAMP)
      assay was developed for rapid detection of EV71. The detection limit of the RT
      LAMP assay was approximately 0.01 PFU per reaction mixture, and no cross-reactive
      amplification with other enteroviruses was observed. The assay was evaluated
      further with 40 clinical specimens and exhibited 92.9% sensitivity and 100%
      specificity. This RT-LAMP assay may become a useful alternative in clinical
      diagnosis of EV71, especially in resource-limited hospitals or rural clinics of
      China and other countries in the Asian-Pacific region.

PMID- 21177908
TI  - Diagnostic performance of filter paper lesion impression PCR for secondarily
      infected ulcers and nonulcerative lesions caused by cutaneous leishmaniasis.
AB  - We compared traditional cutaneous leishmaniasis diagnostic methods to filter
      paper lesion impression (FPLI) PCR for secondarily infected ulcers and
      nonulcerative lesions. The sensitivity and specificity of FPLI PCR for
      secondarily infected lesions (n = 8) were 100%. In primarily nonulcerative
      lesions (n = 15), the sensitivity of FPLI PCR was inferior to that of pooled
      invasive-specimen PCR (72.7% versus 100%) (P = 0.10). FPLI PCR is sensitive,
      specific, and unlike invasive procedures, can be used in secondarily infected
      ulcers. Invasive specimen collection is superior in nonulcerative lesions.

PMID- 21177909
TI  - Genetic diversity of Borrelia burgdorferi and detection of B. bissettii-like DNA
      in serum of north-coastal California residents.
AB  - In North America, Lyme borreliosis (LB) is a tick-borne disease caused by
      infection with the spirochete Borrelia burgdorferi. We studied the genetic
      diversity of LB spirochetes in north-coastal California residents. Spirochete DNA
      was detected in 23.7% (27/114) of the study subjects using a PCR protocol
      optimized for increased sensitivity in human sera. Californians were most
      commonly infected with B. burgdorferi ospC genotype A, a globally widespread
      spirochete associated with high virulence in LB patients. Sequence analysis of
      rrf-rrl and p66 loci in 11% (3/27) of the PCR-positive study subjects revealed
      evidence of infection with an organism closely related to B. bissettii. This
      spirochete, heretofore associated with LB only in Europe, is widely distributed
      among ticks and wildlife in North America. Further molecular testing of sera from
      residents in areas where LB is endemic is warranted to enhance our understanding
      of the geographic distribution and frequency of occurrence of B. bissettii-like
      infections.

PMID- 21177910
TI  - Evaluation of Salmonella-vectored Campylobacter peptide epitopes for reduction of
      Campylobacter jejuni in broiler chickens.
AB  - Campylobacter is a leading cause of bacterial gastroenteritis in humans and is
      often linked to contaminated poultry products. Live Salmonella vectors expressing
      three linear peptide epitopes from Campylobacter proteins Cj0113 (Omp18/CjaD),
      Cj0982c (CjaA), and Cj0420 (ACE393) were administered to chicks by oral gavage on
      the day of hatch, and the chicks were challenged with Campylobacter jejuni on day
      21. All three candidate vaccines produced consistent humoral immune responses
      with high levels of serum IgG and mucosal secretory IgA (sIgA), with the best
      response from the Cj0113 peptide-expressing vector. Campylobacter challenge
      following vaccination of three candidate vaccine groups decreased Campylobacter
      recovery from the ileum compared to that for controls on day 32. The Cj0113
      peptide-expressing vector reduced Campylobacter to below detectable levels. The
      Salmonella-vectored Cj0113 subunit vaccine appears to be an excellent candidate
      for further evaluation as a tool for the reduction of Campylobacter in poultry
      for improved food safety.

PMID- 21177911
TI  - BBK07 immunodominant peptides as serodiagnostic markers of Lyme disease.
AB  - Lyme disease (LD) is a tick-borne infection caused by the bacterial pathogen
      Borrelia burgdorferi. Current diagnostic tests mostly use borrelial lysates or
      select antigens to detect serum antibodies against B. burgdorferi. These
      immunoassays are not entirely effective, especially for detection of early
      infection. We have recently characterized an in vivo-induced antigen, BBK07, as a
      serodiagnostic marker for LD. We now report that in a line blot assay,
      recombinant BBK07 protein-based detection is 90% sensitive and nearly 100%
      specific against B. burgdorferi infection in humans. Using an overlapping peptide
      library of 23 peptides encompassing full-length BBK07, we identified the
      immunodominant epitopes of BBK07 during human infection. We show that a select
      combination of amino-terminal peptides significantly enhanced BBK07-based
      diagnostic accuracy compared to that with the full-length protein. Although in
      enzyme-linked immunosorbent assay (ELISA) studies BBK07 peptides had overall
      lower sensitivity than established serodiagnostic peptides, such as the VlsE
      peptide C6 and OspC peptide pepC10, for the detection of early human LD, a subset
      of serum samples that failed to recognize either VlsE or OspC peptides were
      preferentially reactive to BBK07 peptides. These results highlight the fact that
      BBK07 peptides could be useful to complement the efficacy of VlsE and OspC
      peptide-based serodiagnostic assays. Finally, using a panel of canine sera, we
      show that BBK07 peptide is also effective for LD diagnosis in infected dogs.
      Together, our data show that peptides from the B. burgdorferi surface protein
      BBK07 are highly specific and sensitive serodiagnostic markers, and we suggest
      their future use in LD diagnostic assays.

PMID- 21177912
TI  - Immunogenicity and safety of a multicomponent meningococcal serogroup B vaccine
      and a quadrivalent meningococcal CRM197 conjugate vaccine against serogroups A,
      C, W-135, and Y in adults who are at increased risk for occupational exposure to
      meningococcal isolates.
AB  - Laboratory staff who work with meningococcal isolates are at increased risk for
      developing invasive disease relative to the general population. This was the
      first study of laboratory workers who received both a conjugate vaccine against
      meningococcal serogroups A, C, W-135, and Y (Men ACWY-CRM, Menveo) and an
      investigational multicomponent vaccine against serogroup B containing factor H
      binding protein, neisserial adhesin A, Neisseria heparin binding antigen, and New
      Zealand strain outer membrane vesicles (4CMenB). Healthy adults (18 to 50 years
      of age) received three doses of 4CMenB at baseline, 2 months, and 6 months
      followed by a single dose of MenACWY-CRM 1 month later. Immunogenicity was
      assessed via serum bactericidal assay using human complement (hSBA) at 1 month
      postvaccination; solicited reactogenicity and adverse events were monitored.
      Fifty-four participants enrolled. Bactericidal immune responses were evident
      after each dose of 4CMenB, as assessed by hSBA geometric mean titers and
      percentages of subjects with hSBA titers of >=4 against the test strains or a 4
      fold rise in titer over baseline. At 1 month postvaccination, most MenACWY-CRM
      recipients had hSBA titers of >=8 against serogroups A, C, W-135, and Y. Few
      participants discontinued due to an adverse event or vaccine reaction. Rates of
      solicited reactions were lower after MenACWY-CRM than after 4CMenB
      administration. Sequential administration of 4CMenB and MenACWY-CRM provided
      robust evidence of an immune response against serogroups A, B, C, W-135, and Y in
      laboratory workers routinely exposed to meningococcal isolates.

PMID- 21177913
TI  - Analysis of antibody responses to Mycobacterium leprae phenolic glycolipid I,
      lipoarabinomannan, and recombinant proteins to define disease subtype-specific
      antigenic profiles in leprosy.
AB  - A simple serodiagnostic test based on the Mycobacterium leprae-specific phenolic
      glycolipid I(PGL-I), for individuals with leprosy is nearly universally positive
      in leprosy patients with high bacillary loads but cannot be used as a stand-alone
      diagnostic test for the entire spectrum of the disease process. For patients with
      early infection with no detectable acid-fast bacilli in lesions or with low or no
      antibody titer to PGL-I, as in those at the tuberculoid end of the disease
      spectrum, this diagnostic approach has limited usefulness. To identify additional
      M. leprae antigens that might enhance the serological detection of these
      individuals, we have examined the reactivity patterns of patient sera to PGL-I,
      lipoarabinomannan (LAM), and six recombinant M. leprae proteins (ML1877, ML0841,
      ML2028, ML2038, ML0380, and ML0050) by Western blot analysis and enzyme-linked
      immunosorbent assay (ELISA). Overall, the responses to ML2028 (Ag85B) and ML2038
      (bacterioferritin) were consistently high in both multibacillary and
      paucibacillary groups and weak or absent in endemic controls, while responses to
      other antigens showed considerable variability, from strongly positive to
      completely negative. This analysis has given a clearer understanding of some of
      the differences in the antibody responses between individuals at opposite ends of
      the disease spectrum, as well as illustrating the heterogeneity of antibody
      responses toward protein, carbohydrate, and glycolipid antigens within a clinical
      group. Correlating these response patterns with a particular disease state could
      allow for a more critical assessment of the form of disease within the leprosy
      spectrum and could lead to better patient management.

PMID- 21177914
TI  - Insight toward early diagnosis of leprosy through analysis of the developing
      antibody responses of Mycobacterium leprae-infected armadillos.
AB  - Leprosy is a debilitating chronic disease caused by infection with Mycobacterium
      leprae. A World Health Organization-directed control strategy based upon the
      identification and treatment of patients has resulted in a marked reduction in
      the number of registered worldwide leprosy cases over the last 20 years. Despite
      these efforts, the number of new leprosy cases detected each year now remains
      relatively stable, and M. leprae infection continues to pose a health problem. It
      is suggested that earlier diagnosis is required to strengthen control programs.
      In this study, we have examined the development of antigen-specific
      immunoglobulin responses within armadillos experimentally infected with M. leprae
      to identify those responses that develop most rapidly and robustly following
      infection. Antibody responses to the M. leprae-specific phenolic glycolipid I and
      several protein antigens previously demonstrated to have diagnostic potential
      were assessed. Our results identify several antigens that can provide early
      diagnosis of M. leprae infection but also indicate considerable variability in
      the development of antigen-specific antibodies. Our data suggest that a
      combination of antigens is likely required to provide accurate and early leprosy
      diagnosis.

PMID- 21177915
TI  - Identification, diagnostic potential, and natural expression of immunodominant
      seroreactive peptides encoded by five Mycobacterium tuberculosis-specific genomic
      regions.
AB  - Comparative genomic studies have identified several Mycobacterium tuberculosis
      specific genomic regions of difference (RDs) which are absent in the vaccine
      strains of Mycobacterium bovis BCG and which may be useful in the specific
      diagnosis of tuberculosis (TB). In this study, a total of 775 synthetic peptides
      covering the sequences of 39 open reading frame (ORF) proteins encoded by genes
      predicted in five RDs of M. tuberculosis, i.e., RD1, RD4, RD5, RD6, and RD7, were
      tested by enzyme-linked immunosorbent assays for antibody reactivity with sera
      from HIV-negative pulmonary TB patients (n = 100) and M. bovis BCG-vaccinated
      healthy subjects (n = 100). The results identified three immunodominant peptides
      reactive with TB sera, i.e., amino acids (aa) 346 to 370 of RD1ORF Rv3876, aa 241
      to 265 of RD6ORF Rv1508c, and aa 325 to 336 of RD6ORF Rv1516c. These peptides had
      significantly stronger antibody reactivity with sera from TB patients than with
      sera from healthy subjects (P < 0.05) and significantly higher rates of
      positivity with TB sera (positives = 66 to 93%) than sera from healthy subjects
      (positives = 10 to 28%). Antipeptide antibodies were raised in rabbits after
      immunization with pools of 11 peptides corresponding to each protein. Probing of
      culture filtrates and whole-cell lysates of M. tuberculosis with antipeptide
      antibodies suggested the natural expression of Rv1516c in whole-cell lysates of
      M. tuberculosis. The results suggest the potential of the identified
      immunodominant RD peptides in the serodiagnosis of TB.

PMID- 21177916
TI  - Internalization of IgG-coated targets results in activation and secretion of
      soluble CD40 ligand and RANTES by human platelets.
AB  - Platelets are crucial elements for maintenance of hemostasis. Other functions
      attributable to platelets are now being appreciated, such as their role in
      inflammatory reactions and host defense. Platelets have been reported to bind
      immunological stimuli like IgG complexes, and for nearly 50 years it has been
      speculated that platelets may participate in immunological reactions. Platelets
      have been reported to bind and internalize various substances, similar to other
      leukocytes, such as macrophages and dendritic cells. In the present study, we
      tested the hypothesis that human platelets can bind and internalize IgG-coated
      particles, similar to leukocytes. To this end, we observed that interaction with
      IgG-coated beads resulted in platelet activation (as measured by CD62P
      expression), internalization of targets, and significant soluble CD40 ligand
      (sCD40L) and RANTES (regulated upon activation, normal T cell expresses and
      secreted) secretion. Blocking FcgammaRIIA with monoclonal antibody (MAb) IV.3 or
      inhibiting actin remodeling with cytochalasin D inhibited platelet activation,
      internalization, and cytokine production. These data suggest that platelets are
      capable of mediating internalization of IgG-coated particles, resulting in
      platelet activation and release of both sCD40L and RANTES.

PMID- 21177917
TI  - Development of an immunochromatographic strip for simple detection of penicillin
      binding protein 2'.
AB  - Infections with methicillin-resistant Staphylococcus aureus (MRSA) and
      methicillin-resistant coagulase-negative Staphylococcus (MR-CNS) are a serious
      problem in hospitals because these bacteria produce penicillin-binding protein 2'
      (PBP2' or PBP2a), which shows low affinity to beta-lactam antibiotics.
      Furthermore, the bacteria show resistance to a variety of antibiotics.
      Identification of these pathogens has been carried out mainly by the oxacillin
      susceptibility test, which takes several days to produce a reliable result. We
      developed a simple immunochromatographic test that enabled the detection of PBP2'
      within about 20 min. Anti-PBP2' monoclonal antibodies were produced by a
      hybridoma of recombinant PBP2' (rPBP2')-immunized mouse spleen cells and myeloma
      cells. The monoclonal antibodies reacted only with PBP2' of whole-cell extracts
      and showed no detectable cross-reactivity with extracts from other bacterial
      species tested so far. One of the monoclonal antibodies was conjugated with gold
      colloid particles, which react with PBP2', and another antibody was immobilized
      on a nitrocellulose membrane, which captures the PBP2'-gold colloid particle
      complex on a nitrocellulose strip. This strip was able to detect 1.0 ng of rPBP2'
      or 2.8 * 10(5) to 1.7 * 10(7) CFU of MRSA cells. The cross-reactivity test using
      15 bacterial species and a Candida albicans strain showed no detectable false
      positive results. The accuracy of this method in the detection of MRSA and MR-CNS
      appeared to be 100%, compared with the results obtained by PCR amplification of
      the PBP2' gene, mecA. This newly developed immunochromatographic test can be used
      for simple and accurate detection of PBP2'-producing cells in clinical
      laboratories.

PMID- 21177918
TI  - Induction of foot-and-mouth disease virus-specific cytotoxic T cell killing by
      vaccination.
AB  - Foot-and-mouth disease (FMD) continues to be a significant threat to the health
      and economic value of livestock species. This acute infection is caused by the
      highly contagious FMD virus (FMDV), which infects cloven-hoofed animals,
      including large and small ruminants and swine. Current vaccine strategies are all
      directed toward the induction of neutralizing antibody responses. However, the
      role of cytotoxic T lymphocytes (CTLs) has not received a great deal of
      attention, in part because of the technical difficulties associated with
      establishing a reliable assay of cell killing for this highly cytopathic virus.
      Here, we have used recombinant human adenovirus vectors as a means of delivering
      FMDV antigens in a T cell-directed vaccine in pigs. We tested the hypothesis that
      impaired processing of the FMDV capsid would enhance cytolytic activity,
      presumably by targeting all proteins for degradation and effectively increasing
      the class I major histocompatibility complex (MHC)/FMDV peptide concentration for
      stimulation of a CTL response. We compared such a T cell-targeting vaccine with
      the parental vaccine, previously shown to effectively induce a neutralizing
      antibody response. Our results show induction of FMDV-specific CD8(+) CTL killing
      of MHC-matched target cells in an antigen-specific manner. Further, we confirm
      these results by MHC tetramer staining. This work presents the first
      demonstration of FMDV-specific CTL killing and confirmation by MHC tetramer
      staining in response to vaccination against FMDV.

PMID- 21177919
TI  - Evaluation of serum bactericidal antibody assays for Haemophilus influenzae
      serotype a.
AB  - Haemophilus influenzae type a (Hia) is an important pathogen for some American
      Indian, Alaskan native, and Northern Canada aboriginal populations. Assays to
      measure serum bactericidal activity (SBA) to Hia have not been developed or
      validated. Here, we describe two methods for the measurement of SBA: SBA with a
      viability endpoint (CFU counts) and SBA with a fluorometric endpoint using
      alamarBlue as the metabolic indicator. Both SBA assays measure Hia-specific
      functional antibody and correlate with anti-Hia IgG enzyme-linked immunosorbent
      assay (ELISA) concentration of naturally acquired antibodies.

PMID- 21177920
TI  - Low levels of NF-kappaB/p65 mark anergic CD4+ T cells and correlate with disease
      severity in sarcoidosis.
AB  - T lymphocytes from patients with sarcoidosis respond weakly when stimulated with
      mitogen or antigen. However, the mechanisms responsible for this anergy are not
      fully understood. Here, we investigated the protein levels of nuclear
      transcription factor NF-kappaB (p50, p65, and p105), IkappaBalpha (inhibitor of
      NF-kappaB), T-cell receptor (TCR) CD3zeta-chain, tyrosine kinase p56(LCK), and
      nuclear factor of activated T cells c2 (NF-ATc2) in peripheral blood CD4(+) T
      cells from patients with sarcoidosis. Baseline expression of p65 in these
      lymphocytes was reduced in 50% of patients. The reduced levels of p65 in sarcoid
      CD4(+) T cells concurred with decreased levels of p50, p105, CD3zeta, p56(LCK),
      IkappaBalpha, and NF-ATc2. Polyclonal stimulation of NF-kappaB-deficient sarcoid
      T cells resulted in reduced expression of CD69 and CD154, decreased
      proliferation, and cytokine (i.e., interleukin 2 [IL-2] and gamma interferon [IFN
      gamma]) production. The clinical significance of these findings is suggested by
      the association between low p65 levels and the development of more severe and
      active sarcoidosis. Although correlative, our results support a model in which
      multiple intrinsic signaling defects contribute to peripheral T-cell anergy and
      the persistence of chronic inflammation in sarcoidosis.

PMID- 21177921
TI  - Increasing incidence of Streptococcus pneumoniae serotype 19A and emergence of
      two vaccine escape recombinant ST695 strains in Liguria, Italy, 7 years after
      implementation of the 7-valent conjugated vaccine.
AB  - Two serotype 19A (ST695) Streptococcus pneumoniae vaccine escape recombinant
      strains attributable to capsular switching events were detected by a laboratory
      surveillance system that is an integral part of a vaccination program begun in
      Liguria, Italy, in May 2003, an Italian administrative region with long-lasting
      high coverage, an unusual occurrence in Europe. To our knowledge, this is the
      first detection of an occurrence of capsular switching outside the United States.

PMID- 21177922
TI  - Virulent Newcastle disease virus elicits a strong innate immune response in
      chickens.
AB  - Newcastle disease virus (NDV) is an avian paramyxovirus that causes significant
      economic losses to the poultry industry worldwide. There is limited knowledge
      about the avian immune response to infection with virulent NDVs, and how this
      response may contribute to disease. In this study, pathogenesis and the
      transcriptional host response of chickens to a virulent NDV strain that rapidly
      causes 100% mortality was characterized. Using microarrays, a strong
      transcriptional host response was observed in spleens at early times after
      infection with the induction of groups of genes involved in innate antiviral and
      pro-inflammatory responses. There were multiple genes induced at 48 h post
      infection including: type I and II interferons (IFNs), several cytokines and
      chemokines, IFN effectors and inducible nitric oxide synthase (iNOS). The
      increased transcription of nitric oxide synthase was confirmed by
      immunohistochemistry for iNOS in spleens and measured levels of nitric oxide in
      serum. In vitro experiments showed strong induction of the key host response
      genes, alpha IFN, beta interferon, and interleukin 1beta and interleukin 6, in
      splenic leukocytes at 6 h post-infection in comparison to a non-virulent NDV. The
      robust host response to virulent NDV, in conjunction with severe pathological
      damage observed, is somewhat surprising considering that all NDV encode a gene,
      V, which functions as a suppressor of class I IFNs. Taken together, these results
      suggest that the host response itself may contribute to the pathogenesis of this
      highly virulent strain in chickens.

PMID- 21177923
TI  - Custom-engineered chimeric foot-and-mouth disease vaccine elicits protective
      immune responses in pigs.
AB  - Chimeric foot-and-mouth disease viruses (FMDV) of which the antigenic properties
      can be readily manipulated is a potentially powerful approach in the control of
      foot-and-mouth disease (FMD) in sub-Saharan Africa. FMD vaccine application is
      complicated by the extensive variability of the South African Territories (SAT)
      type viruses, which exist as distinct genetic and antigenic variants in different
      geographical regions. A cross-serotype chimeric virus, vKNP/SAT2, was engineered
      by replacing the external capsid-encoding region (1B-1D/2A) of an infectious cDNA
      clone of the SAT2 vaccine strain, ZIM/7/83, with that of SAT1 virus KNP/196/91.
      The vKNP/SAT2 virus exhibited comparable infection kinetics, virion stability and
      antigenic profiles to the KNP/196/91 parental virus, thus indicating that the
      functions provided by the capsid can be readily exchanged between serotypes. As
      these qualities are necessary for vaccine manufacturing, high titres of stable
      chimeric virus were obtained. Chemically inactivated vaccines, formulated as
      double-oil-in-water emulsions, were produced from intact 146S virion particles of
      both the chimeric and parental viruses. Inoculation of guinea pigs with the
      respective vaccines induced similar antibody responses. In order to show
      compliance with commercial vaccine requirements, the vaccines were evaluated in a
      full potency test. Pigs vaccinated with the chimeric vaccine produced
      neutralizing antibodies and showed protection against homologous FMDV challenge,
      albeit not to the same extent as for the vaccine prepared from the parental
      virus. These results provide support that chimeric vaccines containing the
      external capsid of field isolates can be successfully produced and that they
      induce protective immune responses in FMD host species.

PMID- 21177924
TI  - Global genetic diversity and geographical and host-species distribution of beak
      and feather disease virus isolates.
AB  - Psittacine beak and feather disease (PBFD) has a broad host range and is
      widespread in wild and captive psittacine populations in Asia, Africa, the
      Americas, Europe and Australasia. Beak and feather disease circovirus (BFDV) is
      the causative agent. BFDV has an ~2 kb single stranded circular DNA genome
      encoding just two proteins (Rep and CP). In this study we provide support for
      demarcation of BFDV strains by phylogenetic analysis of 65 complete genomes from
      databases and 22 new BFDV sequences isolated from infected psittacines in South
      Africa. We propose 94% genome-wide sequence identity as a strain demarcation
      threshold, with isolates sharing >94% identity belonging to the same strain, and
      strain subtypes sharing >98% identity. Currently, BFDV diversity falls within 14
      strains, with five highly divergent isolates from budgerigars probably
      representing a new species of circovirus with three strains (budgerigar
      circovirus; BCV-A, -B and -C). The geographical distribution of BFDV and BCV
      strains is strongly linked to the international trade in exotic birds; strains
      with more than one host are generally located in the same geographical area.
      Lastly, we examined BFDV and BCV sequences for evidence of recombination, and
      determined that recombination had occurred in most BFDV and BCV strains. We
      established that there were two globally significant recombination hotspots in
      the viral genome: the first is along the entire intergenic region and the second
      is in the C-terminal portion of the CP ORF. The implications of our results for
      the taxonomy and classification of circoviruses are discussed.

PMID- 21177925
TI  - Detection and characterization of a novel polyomavirus in wild rodents.
AB  - To investigate polyomavirus infection in wild rodents, we analysed DNA samples
      from the spleens of 100 wild rodents from Zambia using a broad-spectrum PCR-based
      assay. A previously unknown polyomavirus genome was identified in a sample from a
      multimammate mouse (Mastomys species) and the entire viral genome of 4899 bp was
      subsequently sequenced. This viral genome contained potential ORFs for the capsid
      proteins, VP1, VP2 and VP3, and early proteins, small t antigen and large T
      antigen. Phylogenetic analysis showed that it was a novel member of the family
      Polyomaviridae, and thus the virus was tentatively named mastomys polyomavirus.
      After transfection of the viral genome into several mammalian cell lines,
      transient expression of the VP1 and large T antigen proteins was confirmed by
      immunoblotting and immunocytochemical analyses. Comparison of large T antigen
      function in mastomys polyomavirus with that in rhesus monkey polyomavirus SV40
      and human polyomavirus JC virus revealed that the large T antigen from mastomys
      polyomavirus interacted with the tumour suppressor protein pRb, but not with p53.

PMID- 21177927
TI  - Different contribution of bovine papillomavirus type 1 oncoproteins to the
      transformation of equine fibroblasts.
AB  - Equine sarcoids represent the most common skin tumours in equids worldwide,
      characterized by localized invasion, rare regression and high recurrence
      following surgical intervention. Bovine papillomavirus type 1 (BPV-1) and less
      commonly BPV-2 are now widely recognized as the causative agents of the disease.
      Fibroblasts isolated from sarcoids are highly invasive. Invasion is associated
      with a high level of viral gene expression and matrix metalloproteinase
      upregulation. However, it remains unclear to what extent BPV-1 proteins are
      involved in the transformation of equine cells. To address this question, the
      individual viral genes E5, E6 and E7 were overexpressed in normal equine
      fibroblasts (EqPalF cells) and in the immortal but not fully transformed sarcoid
      derived EqS02a cell line. The proliferation and invasiveness of these cell lines
      were assessed. E5 and E6 were found to be responsible for the enhanced cell
      proliferation and induction of increased invasion in EqS02a cells, whilst E7
      appeared to enhance cell anchorage independence. Knockdown of BPV-1 oncogene
      expression by small interfering RNA reversed the transformed phenotype of sarcoid
      fibroblasts. Together, these observations strongly suggest that BPV-1 proteins
      play indispensable roles in the transformation of equine fibroblasts. These data
      also suggest that BPV-1 proteins are potential drug targets for equine sarcoid
      therapy.

PMID- 21177926
TI  - Genetic and antigenic characterization of H1 influenza viruses from United States
      swine from 2008.
AB  - Prior to the introduction of the 2009 pandemic H1N1 virus from humans into pigs,
      four phylogenetic clusters (alpha-, beta-, gamma- and delta) of the
      haemagglutinin (HA) gene from H1 influenza viruses could be found in US swine.
      Information regarding the antigenic relatedness of the H1 viruses was lacking due
      to the dynamic and variable nature of swine lineage H1. We characterized 12 H1
      isolates from 2008 by using 454 genome-sequencing technology and phylogenetic
      analysis of all eight gene segments and by serological cross-reactivity in the
      haemagglutination inhibition (HI) assay. Genetic diversity was demonstrated in
      all gene segments, but most notably in the HA gene. The gene segments from the
      2009 pandemic H1N1 formed clusters separate from North American swine lineage
      viruses, suggesting progenitors of the pandemic virus were not present in US pigs
      immediately prior to 2009. Serological cross-reactivity paired with antigenic
      cartography demonstrated that the viruses in the different phylogenetic clusters
      are also antigenically divergent.

PMID- 21177928
TI  - Possible cross-species transmission of circoviruses and cycloviruses among farm
      animals.
AB  - Circoviruses consist of highly prevalent and genetically diverse porcine and
      avian pathogens. The genomes of cycloviruses, a proposed new genus in the family
      Circoviridae, were recently identified in human and chimpanzee faeces. Here, six
      cyclovirus and four circovirus genomes from the tissues of chickens, goats, cows,
      and a bat were amplified and sequenced using rolling-circle amplification and
      inverse PCR. A goat cyclovirus was nearly identical to a cyclovirus from a cow.
      USA beef contained circoviruses with >99% similarity to porcine circovirus 2b.
      Circoviruses in chicken were related to those of pigeons. The close genetic
      similarity of a subset of cycloviruses and circoviruses replicating in distinct
      animal species may reflect recent cross-species transmissions. Further studies
      will be required to determine the impact of these highly prevalent infections on
      the health of farm animals.

PMID- 21177929
TI  - The subcellular localization of the hepatitis C virus non-structural protein NS2
      is regulated by an ion channel-independent function of the p7 protein.
AB  - The hepatitis C virus (HCV) p7 ion channel and non-structural protein 2 (NS2) are
      both required for efficient assembly and release of nascent virions, yet
      precisely how these proteins are able to influence this process is unclear. Here,
      we provide both biochemical and cell biological evidence for a functional
      interaction between p7 and NS2. We demonstrate that in the context of a genotype
      1b subgenomic replicon the localization of NS2 is affected by the presence of an
      upstream p7 with its cognate signal peptide derived from the C terminus of E2
      (SPp7). Immunofluorescence analysis revealed that the presence of SPp7 resulted
      in the targeting of NS2 to sites closely associated with viral replication
      complexes. In addition, biochemical analysis demonstrated that, in the presence
      of SPp7, a significant proportion of NS2 was found in a detergent (Triton X-100)
      insoluble fraction, which also contained a marker of detergent resistant rafts.
      In contrast, in replicons lacking p7, NS2 was entirely detergent soluble and the
      altered localization was lost. Furthermore, we found that serine 168 within NS2
      was required for its localization adjacent to replication complexes, but not for
      its accumulation in the detergent-insoluble fraction. NS2 physically interacted
      with NS5A and this interaction was dependent on both p7 and serine 168 within
      NS2. Mutational and pharmacological analyses demonstrated that these effects were
      not a consequence of p7 ion channel function, suggesting that p7 possesses an
      alternative function that may influence the coordination of virus genome
      replication and particle assembly.

PMID- 21177930
TI  - Persistence of bacteriophage T4 in a starved Escherichia coli culture: evidence
      for the presence of phage subpopulations.
AB  - Bacteriophage T4 is able to adjust its development to the growth parameters of
      the host cell. Here, we present evidence for the production of two different
      subpopulations of phage particles, which differ in their ability to infect
      starved Escherichia coli cells. The ability of phage T4 to produce a fraction of
      virions unable to infect starved cells is linked to the functions of genes rI and
      rIII, as well as rIIA. This may represent the adaptation of phage T4 in order to
      persist in unfavourable environmental conditions.

PMID- 21177931
TI  - Retraction. Activation of intercellular adhesion molecule 1 expression by
      Helicobacter pylori is regulated by NF-kappaB in gastric epithelial cancer cells.

PMID- 21177932
TI  - Retraction. Induction of monocyte chemoattractant protein 1 by Helicobacter
      pylori involves NF-kappaB.

PMID- 21177934
TI  - Retraction. Helicobacter pylori induces CCL20 expression.

PMID- 21177933
TI  - Retraction. Helicobacter pylori induces RANTES through activation of NF-kappaB.

PMID- 21177935
TI  - Retraction. Helicobacter pylori-induced interleukin-12 p40 expression.

PMID- 21177936
TI  - The biology of energy expenditure.

PMID- 21177938
TI  - The sugar oxidation cascade: aerial refueling in hummingbirds and nectar bats.
AB  - Most hummingbirds and some species of nectar bats hover while feeding on floral
      nectar. While doing so, they achieve some of the highest mass-specific V(O(2))
      values among vertebrates. This is made possible by enhanced functional capacities
      of various elements of the 'O(2) transport cascade', the pathway of O(2) from the
      external environment to muscle mitochondria. Fasted hummingbirds and nectar bats
      fly with respiratory quotients (RQs; V(CO(2))/V(O(2))) of ~0.7, indicating that
      fat fuels flight in the fasted state. During repeated hover-feeding on dietary
      sugar, RQ values progressively climb to ~1.0, indicating a shift from fat to
      carbohydrate oxidation. Stable carbon isotope experiments reveal that recently
      ingested sugar directly fuels ~80 and 95% of energy metabolism in hover-feeding
      nectar bats and hummingbirds, respectively. We name the pathway of carbon flux
      from flowers, through digestive and cardiovascular systems, muscle membranes and
      into mitochondria the 'sugar oxidation cascade'. O(2) and sugar oxidation
      cascades operate in parallel and converge in muscle mitochondria. Foraging
      behavior that favours the oxidation of dietary sugar avoids the inefficiency of
      synthesizing fat from sugar and breaking down fat to fuel foraging. Sugar
      oxidation yields a higher P/O ratio (ATP made per O atom consumed) than fat
      oxidation, thus requiring lower hovering V(O(2)) per unit mass. We propose that
      dietary sugar is a premium fuel for flight in nectarivorous, flying animals.

PMID- 21177937
TI  - Molecular population genetics and selection in the glycolytic pathway.
AB  - In this review, I discuss the evidence for differential natural selection acting
      across enzymes in the glycolytic pathway in Drosophila. Across the genome, genes
      evolve at very different rates and possess markedly varying levels of molecular
      polymorphism, codon bias and expression variation. Discovering the underlying
      causes of this variation has been a challenge in evolutionary biology. It has
      been proposed that both the intrinsic properties of enzymes and their pathway
      position have direct effects on their molecular evolution, and with the genomic
      era the study of adaptation has been taken to the level of pathways and networks
      of genes and their products. Of special interest have been the energy-producing
      pathways. Using both population genetic and experimental approaches, our
      laboratory has been engaged in a study of molecular variation across the
      glycolytic pathway in Drosophila melanogaster and its close relatives. We have
      observed a pervasive pattern in which genes at the top of the pathway, especially
      around the intersection at glucose 6-phosphate, show evidence for both
      contemporary selection, in the form of latitudinal allele clines, and inter
      specific selection, in the form of elevated levels of amino acid substitutions
      between species. To further explore this question, future work will require
      corroboration in other species, expansion into tangential pathways, and
      experimental work to better characterize metabolic control through the pathway
      and to examine the pleiotropic effects of these genes on other traits and fitness
      components.

PMID- 21177939
TI  - Microevolution of intermediary metabolism: evolutionary genetics meets metabolic
      biochemistry.
AB  - During the past decade, microevolution of intermediary metabolism has become an
      important new research focus at the interface between metabolic biochemistry and
      evolutionary genetics. Increasing recognition of the importance of integrative
      studies in evolutionary analysis, the rising interest in 'evolutionary systems
      biology', and the development of various 'omics' technologies have all
      contributed significantly to this developing interface. The present review
      primarily focuses on five prominent areas of recent research on pathway
      microevolution: lipid metabolism and life-history evolution; the electron
      transport system, hybrid breakdown and speciation; glycolysis, alcohol metabolism
      and population adaptation in Drosophila; chemostat selection in microorganisms;
      and anthocyanin pigment biosynthesis and flower color evolution. Some of these
      studies have provided a new perspective on important evolutionary topics that
      have not been investigated extensively from a biochemical perspective (hybrid
      breakdown, parallel evolution). Other studies have provided new data that augment
      previous biochemical information, resulting in a deeper understanding of
      evolutionary mechanisms (allozymes and biochemical adaptation to climate, life
      history evolution, flower pigments and the genetics of adaptation). Finally,
      other studies have provided new insights into how the function or position of an
      enzyme in a pathway influences its evolutionary dynamics, in addition to
      providing powerful experimental models for investigations of network evolution.
      Microevolutionary studies of metabolic pathways will undoubtedly become
      increasingly important in the future because of the central importance of
      intermediary metabolism in organismal fitness, the wealth of biochemical data
      being provided by various omics technologies, and the increasing influence of
      integrative and systems perspectives in biology.

PMID- 21177940
TI  - Physiological, behavioral and biochemical adaptations of intertidal fishes to
      hypoxia.
AB  - Hypoxia survival in fish requires a well-coordinated response to either secure
      more O(2) from the hypoxic environment or to limit the metabolic consequences of
      an O(2) restriction at the mitochondria. Although there is a considerable amount
      of information available on the physiological, behavioral, biochemical and
      molecular responses of fish to hypoxia, very little research has attempted to
      determine the adaptive value of these responses. This article will review current
      attempts to use the phylogenetically corrected comparative method to define
      physiological and behavioral adaptations to hypoxia in intertidal fish and
      further identify putatively adaptive biochemical traits that should be
      investigated in the future. In a group of marine fishes known as sculpins, from
      the family Cottidae, variation in hypoxia tolerance, measured as a critical O(2)
      tension (P(crit)), is primarily explained by variation in mass-specific gill
      surface area, red blood cell hemoglobin-O(2) binding affinity, and to a lesser
      extent variation in routine O(2) consumption rate (M(O(2))). The most hypoxia
      tolerant sculpins consistently show aquatic surface respiration (ASR) and aerial
      emergence behavior during hypoxia exposure, but no phylogenetically independent
      relationship has been found between the thresholds for initiating these behaviors
      and P(crit). At O(2) levels below P(crit), hypoxia survival requires a rapid
      reorganization of cellular metabolism to suppress ATP consumption to match the
      limited capacity for O(2)-independent ATP production. Thus, it is reasonable to
      speculate that the degree of metabolic rate suppression and the quantity of
      stored fermentable fuel is strongly selected for in hypoxia-tolerant fishes;
      however, these assertions have not been tested in a phylogenetic comparative
      model.

PMID- 21177941
TI  - Energetic cost of communication.
AB  - Communication signals may be energetically expensive or inexpensive to produce,
      depending on the function of the signal and the competitive nature of the
      communication system. Males of sexually selected species may produce high-energy
      advertisement signals, both to enhance detectability and to signal their size and
      body condition. Accordingly, the proportion of the energy budget allocated to
      signal production ranges from almost nothing for many signals to somewhere in
      excess of 50% for acoustic signals in short-lived sexually selected species.
      Recent data from gymnotiform electric fish reveal mechanisms that regulate energy
      allocated to sexual advertisement signals through dynamical remodeling of the
      excitable membranes in the electric organ. Further, males of the short-lived
      sexually selected species, Brachyhypopomus gauderio, trade off among different
      metabolic compartments, allocating energy to signal production while reducing
      energy used in other metabolic functions. Female B. gauderio, by contrast, do not
      trade off energy between signaling and other functions. To fuel energetically
      expensive signal production, we expect a continuum of strategies to be adopted by
      animals of different life history strategies. Future studies should explore the
      relation between life history and energy allocation trade-offs.

PMID- 21177943
TI  - Limits to sustained energy intake. XIII. Recent progress and future perspectives.
AB  - Several theories have been proposed to explain limits on the maximum rate at
      which animals can ingest and expend energy. These limits are likely to be
      intrinsic to the animal, and potentially include the capacity of the alimentary
      tract to assimilate energy--the 'central limitation' hypothesis. Experimental
      evidence from lactating mice exposed to different ambient temperatures allows us
      to reject this and similar ideas. Two alternative ideas have been proposed. The
      'peripheral limitation' hypothesis suggests that the maximal sustained energy
      intake reflects the summed demands of individual tissues, which have their own
      intrinsic limitations on capacity. In contrast, the 'heat dissipation limit'
      (HDL) theory suggests that animals are constrained by the maximal capacity to
      dissipate body heat. Abundant evidence in domesticated livestock supports the HDL
      theory, but data from smaller mammals are less conclusive. Here, we develop a
      novel framework showing how the HDL and peripheral limitations are likely to be
      important in all animals, but to different extents. The HDL theory makes a number
      of predictions--in particular that there is no fixed limit on sustained energy
      expenditure as a multiple of basal metabolic rate, but rather that the maximum
      sustained scope is positively correlated with the capacity to dissipate heat.

PMID- 21177944
TI  - Nonshivering thermogenesis and its adequate measurement in metabolic studies.
AB  - Alterations in nonshivering thermogenesis are presently discussed as being both
      potentially causative of and able to counteract obesity. However, the necessity
      for mammals to defend their body temperature means that the ambient temperature
      profoundly affects the outcome and interpretation of metabolic experiments. An
      adequate understanding and assessment of nonshivering thermogenesis is therefore
      paramount for metabolic studies. Classical nonshivering thermogenesis is
      facultative, i.e. it is only activated when an animal acutely requires extra heat
      (switched on in minutes), and adaptive, i.e. it takes weeks for an increase in
      capacity to develop. Nonshivering thermogenesis is fully due to brown adipose
      tissue activity; adaptation corresponds to the recruitment of this tissue. Diet
      induced thermogenesis is probably also facultative and adaptive and due to brown
      adipose tissue activity. Although all mammals respond to injected/infused
      norepinephrine (noradrenaline) with an increase in metabolism, in non-adapted
      mammals this increase mainly represents the response of organs not involved in
      nonshivering thermogenesis; only the increase after adaptation represents
      nonshivering thermogenesis. Thermogenesis (metabolism) should be expressed per
      animal, and not per body mass [not even to any power (0.75 or 0.66)]. A 'cold
      tolerance test' does not examine nonshivering thermogenesis capacity; rather it
      tests shivering capacity and endurance. For mice, normal animal house
      temperatures are markedly below thermoneutrality, and the mice therefore have a
      metabolic rate and food consumption about 1.5 times higher than their intrinsic
      requirements. Housing and examining mice at normal house temperatures carries a
      high risk of identifying false positives for intrinsic metabolic changes; in
      particular, mutations/treatments that affect the animal's insulation (fur, skin)
      may lead to such problems. Correspondingly, true alterations in intrinsic
      metabolic rate remain undetected when metabolism is examined at temperatures
      below thermoneutrality. Thus, experiments with animals kept and examined at
      thermoneutrality are likely to yield an improved possibility of identifying
      agents and genes important for human energy balance.

PMID- 21177947
TI  - Mitochondrial biogenesis in cold-bodied fishes.
AB  - Mitochondrial biogenesis is induced in response to cold temperature in many
      organisms. The effect is particularly pronounced in ectotherms such as fishes,
      where acclimation to cold temperature increases mitochondrial density. Some polar
      fishes also have exceptionally high densities of mitochondria. The net effect of
      increasing mitochondrial density is threefold. First, it increases the
      concentration of aerobic metabolic enzymes per gram of tissue, maintaining ATP
      production. Second, it elevates the density of mitochondrial membrane
      phospholipids, enhancing rates of intracellular oxygen diffusion. Third, it
      reduces the diffusion distance for oxygen and metabolites between capillaries and
      mitochondria. Although cold-induced mitochondrial biogenesis has been well
      documented in fishes, little is known about the molecular pathway governing it.
      In mammals, the co-transcriptional activator peroxisome proliferator-activated
      receptor gamma coactivator 1 alpha (PGC-1alpha) is thought to coordinate the
      three components of mitochondrial biogenesis: the synthesis of mitochondrial
      proteins, the synthesis of phospholipids and the replication of mitochondrial
      DNA. Some components of the mitochondrial biogenic pathway are conserved between
      fishes and mammals, yet the pathway appears more versatile in fishes. In some
      tissues of cold-acclimated fishes, the synthesis of mitochondrial proteins
      increases in the absence of an increase in phospholipids, whereas in some polar
      fishes, densities of mitochondrial phospholipids increase in the absence of an
      increase in proteins. The ability of cold-bodied fishes to fine-tune the
      mitochondrial biogenic pathway may allow them to modify mitochondrial
      characteristics to meet the specific needs of the cell, whether it is to increase
      ATP production or enhance oxygen diffusion.

PMID- 21177946
TI  - Molecules in motion: influences of diffusion on metabolic structure and function
      in skeletal muscle.
AB  - Metabolic processes are often represented as a group of metabolites that interact
      through enzymatic reactions, thus forming a network of linked biochemical
      pathways. Implicit in this view is that diffusion of metabolites to and from
      enzymes is very fast compared with reaction rates, and metabolic fluxes are
      therefore almost exclusively dictated by catalytic properties. However, diffusion
      may exert greater control over the rates of reactions through: (1) an increase in
      reaction rates; (2) an increase in diffusion distances; or (3) a decrease in the
      relevant diffusion coefficients. It is therefore not surprising that skeletal
      muscle fibers have long been the focus of reaction-diffusion analyses because
      they have high and variable rates of ATP turnover, long diffusion distances, and
      hindered metabolite diffusion due to an abundance of intracellular barriers.
      Examination of the diversity of skeletal muscle fiber designs found in animals
      provides insights into the role that diffusion plays in governing both rates of
      metabolic fluxes and cellular organization. Experimental measurements of
      metabolic fluxes, diffusion distances and diffusion coefficients, coupled with
      reaction-diffusion mathematical models in a range of muscle types has started to
      reveal some general principles guiding muscle structure and metabolic function.
      Foremost among these is that metabolic processes in muscles do, in fact, appear
      to be largely reaction controlled and are not greatly limited by diffusion.
      However, the influence of diffusion is apparent in patterns of fiber growth and
      metabolic organization that appear to result from selective pressure to maintain
      reaction control of metabolism in muscle.

PMID- 21177948
TI  - Metabolic fuels: regulating fluxes to select mix.
AB  - Animals must regulate the fluxes of multiple fuels to support changing metabolic
      rates that result from variation in physiological circumstances. The aim of fuel
      selection strategies is to exploit the advantages of individual substrates while
      minimizing the impact of disadvantages. All exercising mammals share a general
      pattern of fuel selection: at the same %V(O(2,max)) they oxidize the same ratio
      of lipids to carbohydrates. However, highly aerobic species rely more on
      intramuscular fuels because energy supply from the circulation is constrained by
      trans-sarcolemmal transfer. Fuel selection is performed by recruiting different
      muscles, different fibers within the same muscles or different pathways within
      the same fibers. Electromyographic analyses show that shivering humans can
      modulate carbohydrate oxidation either through the selective recruitment of type
      II fibers within the same muscles or by regulating pathway recruitment within
      type I fibers. The selection patterns of shivering and exercise are different: at
      the same %V(O(2,max)), a muscle producing only heat (shivering) or significant
      movement (exercise) strikes a different balance between lipid and carbohydrate
      oxidation. Long-distance migrants provide an excellent model to characterize how
      to increase maximal substrate fluxes. High lipid fluxes are achieved through the
      coordinated upregulation of mobilization, transport and oxidation by activating
      enzymes, lipid-solubilizing proteins and membrane transporters. These endurance
      athletes support record lipolytic rates in adipocytes, use lipoprotein shuttles
      to accelerate transport and show increased capacity for lipid oxidation in muscle
      mitochondria. Some migrant birds use dietary omega-3 fatty acids as performance
      enhancing agents to boost their ability to process lipids. These dietary fatty
      acids become incorporated in membrane phospholipids and bind to peroxisome
      proliferator-activated receptors to activate membrane proteins and modify gene
      expression.

PMID- 21177945
TI  - The physiological regulation of glucose flux into muscle in vivo.
AB  - Skeletal muscle glucose uptake increases dramatically in response to physical
      exercise. Moreover, skeletal muscle comprises the vast majority of insulin
      sensitive tissue and is a site of dysregulation in the insulin-resistant state.
      The biochemical and histological composition of the muscle is well defined in a
      variety of species. However, the functional consequences of muscle biochemical
      and histological adaptations to physiological and pathophysiological conditions
      are not well understood. The physiological regulation of muscle glucose uptake is
      complex. Sites involved in the regulation of muscle glucose uptake are defined by
      a three-step process consisting of: (1) delivery of glucose to muscle, (2)
      transport of glucose into the muscle by GLUT4 and (3) phosphorylation of glucose
      within the muscle by a hexokinase (HK). Muscle blood flow, capillary recruitment
      and extracellular matrix characteristics determine glucose movement from the
      blood to the interstitium. Plasma membrane GLUT4 content determines glucose
      transport into the cell. Muscle HK activity, cellular HK compartmentalization and
      the concentration of the HK inhibitor glucose 6-phosphate determine the capacity
      to phosphorylate glucose. Phosphorylation of glucose is irreversible in muscle;
      therefore, with this reaction, glucose is trapped and the uptake process is
      complete. Emphasis has been placed on the role of the glucose transport step for
      glucose influx into muscle with the past assertion that membrane transport is
      rate limiting. More recent research definitively shows that the distributed
      control paradigm more accurately defines the regulation of muscle glucose uptake
      as each of the three steps that define this process are important sites of flux
      control.

PMID- 21177942
TI  - The biological control of voluntary exercise, spontaneous physical activity and
      daily energy expenditure in relation to obesity: human and rodent perspectives.
AB  - Mammals expend energy in many ways, including basic cellular maintenance and
      repair, digestion, thermoregulation, locomotion, growth and reproduction. These
      processes can vary tremendously among species and individuals, potentially
      leading to large variation in daily energy expenditure (DEE). Locomotor energy
      costs can be substantial for large-bodied species and those with high-activity
      lifestyles. For humans in industrialized societies, locomotion necessary for
      daily activities is often relatively low, so it has been presumed that activity
      energy expenditure and DEE are lower than in our ancestors. Whether this is true
      and has contributed to a rise in obesity is controversial. In humans, much
      attention has centered on spontaneous physical activity (SPA) or non-exercise
      activity thermogenesis (NEAT), the latter sometimes defined so broadly as to
      include all energy expended due to activity, exclusive of volitional exercise.
      Given that most people in Western societies engage in little voluntary exercise,
      increasing NEAT may be an effective way to maintain DEE and combat overweight and
      obesity. One way to promote NEAT is to decrease the amount of time spent on
      sedentary behaviours (e.g. watching television). The effects of voluntary
      exercise on other components of physical activity are highly variable in humans,
      partly as a function of age, and have rarely been studied in rodents. However,
      most rodent studies indicate that food consumption increases in the presence of
      wheels; therefore, other aspects of physical activity are not reduced enough to
      compensate for the energetic cost of wheel running. Most rodent studies also show
      negative effects of wheel access on body fat, especially in males. Sedentary
      behaviours per se have not been studied in rodents in relation to obesity.
      Several lines of evidence demonstrate the important role of dopamine, in addition
      to other neural signaling networks (e.g. the endocannabinoid system), in the
      control of voluntary exercise. A largely separate literature points to a key role
      for orexins in SPA and NEAT. Brain reward centers are involved in both types of
      physical activities and eating behaviours, likely leading to complex
      interactions. Moreover, voluntary exercise and, possibly, eating can be
      addictive. A growing body of research considers the relationships between
      personality traits and physical activity, appetite, obesity and other aspects of
      physical and mental health. Future studies should explore the neurobiology,
      endocrinology and genetics of physical activity and sedentary behaviour by
      examining key brain areas, neurotransmitters and hormones involved in motivation,
      reward and/or the regulation of energy balance.

PMID- 21177949
TI  - Why marathon migrants get away with high metabolic ceilings: towards an ecology
      of physiological restraint.
AB  - Animals usually are not willing to perform at levels, or for lengths of time, of
      which they should be maximally capable. In stating this, exercise performance and
      inferred capacity are gauged with respect to body size and the duration of
      particular levels of energy expenditure. In such relative terms, the long-term
      metabolic ceiling of ca. 7 times basal metabolic rate in challenged but energy
      balanced individuals may be real and general, because greater performance over
      long periods requires larger metabolic machinery that is ever more expensive to
      maintain. Avian marathon migrants relying on stored fuel (and therefore not in
      energy balance) that work for 9 consecutive days at levels of 9-10 times basal
      metabolic rate are exceptional performers in terms of the 'relative expenditure'
      on 'duration of a particular activity' curve nevertheless. Here I argue that
      metabolic ceilings in all situations (energy balanced or not) have their origin
      in the fitness costs of high performance levels due to subsequently reduced
      survival, which then precludes the possibility of future reproduction. The limits
      to performance should therefore be studied relative to ecological context (which
      includes aspects such as pathogen pressure and risk of overheating), which
      determines the severity of the survival punishment of over-exertion. I conclude
      that many dimensions of ecology have determined at which performance levels
      (accounting for time) individual animals, including human athletes, begin to show
      physiological restraint. Using modern molecular techniques to assay wear and
      tear, in combination with manipulated work levels in different ecological
      contexts, might enable experimental verification of these ideas.

PMID- 21177951
TI  - The metabolic demands of endosymbiotic chemoautotrophic metabolism on host
      physiological capacities.
AB  - While chemoautotrophic endosymbioses of hydrothermal vents and other reducing
      environments have been well studied, little attention has been paid to the
      magnitude of the metabolic demands placed upon the host by symbiont metabolism
      and the adaptations necessary to meet such demands. Here we make the first
      attempt at such an evaluation, and show that moderate to high rates of
      chemoautotrophic or methanotrophic metabolism impose oxygen uptake and proton
      equivalent elimination demands upon the hosts that are much higher than is
      typical for the non-symbiotic annelid, bivalve and gastropod lineages to which
      they are related. The properties of the hosts are described and compared to
      determine which properties are associated with and predictive of the highest
      rates. We suggest that the high oxygen demand of these symbionts is perhaps the
      most limiting flux for the symbioses. Among the consequences of such demands has
      been the widespread presence of circulating and/or tissue hemoglobins in these
      symbioses that are necessary to support high metabolic rates in thioautotrophic
      endosymbioses. We also compare photoautotrophic with chemoautotrophic and
      methanotrophic endosymbioses to evaluate the differences and similarities in
      physiologies. These analyses suggest that the high demand for oxygen by
      chemoautotrophic and methanotrophic symbionts is likely a major factor precluding
      their endosymbiosis with cnidarians.

PMID- 21177950
TI  - The making of a photosynthetic animal.
AB  - Symbiotic animals containing green photobionts challenge the common perception
      that only plants are capable of capturing the sun's rays and converting them into
      biological energy through photoautotrophic CO(2) fixation (photosynthesis).
      'Solar-powered' sacoglossan molluscs, or sea slugs, have taken this type of
      symbiotic association one step further by solely harboring the photosynthetic
      organelle, the plastid (=chloroplast). One such sea slug, Elysia chlorotica,
      lives as a 'plant' when provided with only light and air as a result of acquiring
      plastids during feeding on its algal prey Vaucheria litorea. The captured
      plastids (kleptoplasts) are retained intracellularly in cells lining the
      digestive diverticula of the sea slug, a phenomenon sometimes referred to as
      kleptoplasty. Photosynthesis by the plastids provides E. chlorotica with energy
      and fixed carbon for its entire lifespan of ~10 months. The plastids are not
      transmitted vertically (i.e. are absent in eggs) and do not undergo division in
      the sea slug. However, de novo protein synthesis continues, including plastid-
      and nuclear-encoded plastid-targeted proteins, despite the apparent absence of
      algal nuclei. Here we discuss current data and provide hypotheses to explain how
      long-term photosynthetic activity is maintained by the kleptoplasts. This
      fascinating 'green animal' provides a unique model to study the evolution of
      photosynthesis in a multicellular heterotrophic organism.

PMID- 21177952
TI  - Critical oxygen levels and metabolic suppression in oceanic oxygen minimum zones.
AB  - The survival of oceanic organisms in oxygen minimum zones (OMZs) depends on their
      total oxygen demand and the capacities for oxygen extraction and transport,
      anaerobic ATP production and metabolic suppression. Anaerobic metabolism and
      metabolic suppression are required for daytime forays into the most extreme OMZs.
      Critical oxygen partial pressures are, within a range, evolved to match the
      minimum oxygen level to which a species is exposed. This fact demands that low
      oxygen habitats be defined by the biological response to low oxygen rather than
      by some arbitrary oxygen concentration. A broad comparative analysis of oxygen
      tolerance facilitates the identification of two oxygen thresholds that may prove
      useful for policy makers as OMZs expand due to climate change. Between these
      thresholds, specific physiological adaptations to low oxygen are required of
      virtually all species. The lower threshold represents a limit to evolved oxygen
      extraction capacity. Climate change that pushes oxygen concentrations below the
      lower threshold (~0.8 kPa) will certainly result in a transition from an
      ecosystem dominated by a diverse midwater fauna to one dominated by diel migrant
      biota that must return to surface waters at night. Animal physiology and, in
      particular, the response of animals to expanding hypoxia, is a critical, but
      understudied, component of biogeochemical cycles and oceanic ecology. Here, I
      discuss the definition of hypoxia and critical oxygen levels, review adaptations
      of animals to OMZs and discuss the capacity for, and prevalence of, metabolic
      suppression as a response to temporary residence in OMZs and the possible
      consequences of climate change on OMZ ecology.

PMID- 21177953
TI  - Muscles and their myokines.
AB  - In the past, the role of physical activity as a life-style modulating factor has
      been considered as that of a tool to balance energy intake. Although it is
      important to avoid obesity, physical inactivity should be discussed in a much
      broader context. There is accumulating epidemiological evidence that a physically
      active life plays an independent role in the protection against type 2 diabetes,
      cardiovascular diseases, cancer, dementia and even depression. For most of the
      last century, researchers sought a link between muscle contraction and humoral
      changes in the form of an 'exercise factor', which could be released from
      skeletal muscle during contraction and mediate some of the exercise-induced
      metabolic changes in other organs such as the liver and the adipose tissue. We
      have suggested that cytokines or other peptides that are produced, expressed and
      released by muscle fibres and exert autocrine, paracrine or endocrine effects
      should be classified as 'myokines'. Given that skeletal muscle is the largest
      organ in the human body, our discovery that contracting skeletal muscle secretes
      proteins sets a novel paradigm: skeletal muscle is an endocrine organ producing
      and releasing myokines, which work in a hormone-like fashion, exerting specific
      endocrine effects on other organs. Other myokines work via paracrine mechanisms,
      exerting local effects on signalling pathways involved in muscle metabolism. It
      has been suggested that myokines may contribute to exercise-induced protection
      against several chronic diseases.

PMID- 21177954
TI  - Overlap of quantitative trait loci for early growth rate, and for body weight and
      age at onset of sexual maturity in chickens.
AB  - Critical age, weight and body composition have been suggested as necessary
      correlates of sexual maturity. A genome scan to identify quantitative trait loci
      (QTL) for age and body weight at first egg (AFE and WFE) was conducted on 912
      birds from an F(2) broiler-layer cross using 106 microsatellite markers. Without
      a covariate, QTL for body WFE were detected on chromosomes 2, 4, 8, 27 and Z and
      a single QTL for AFE was detected on chromosome 2. With AFE as a covariate,
      additional QTL for body WFE were found on chromosomes 1 and 13, with abdominal
      fat pad as covariate a QTL for body WFE was found on chromosome 1. With body WFE
      as covariate, additional QTL for AFE were found on chromosomes 1, 3, 4, 13 and
      27. The QTL generally acted additively and there was no evidence for epistasis.
      Consistent with the original line differences, broiler alleles had positive
      effects on body WFE and negative effects on AFE, whereas the phenotypic
      correlation between the two traits was positive. The mapped QTL for body WFE
      cumulatively accounted for almost half the body weight difference between the
      chicken lines at puberty. Overlapping QTL for body WFE and body weight to 9 weeks
      of age indicate that most QTL affecting growth rate also affect body WFE. The co
      localisation of QTL for body weight, growth and sexual maturity suggests that
      body weight and growth rate are closely related to the attainment of sexual
      maturity and that the genetic determination of growth rate has correlated effects
      on puberty.

PMID- 21177955
TI  - Characterization and biological activity of relaxin in porcine milk.
AB  - A lactocrine mechanism for delivery of maternally derived relaxin (RLX) into the
      neonatal circulation as a consequence of nursing was proposed for the pig.
      Immunoreactive RLX was detected in colostrum and in the serum of newborn pigs
      only if they were allowed to nurse. Milk-borne RLX concentrations are highest
      during early lactation (9-19  ng/ml), declining to <2  ng/ml by postnatal day 14.
      Whether milk-borne RLX is bioactive is unknown. Evidence that RLX concentrations
      in milk are higher than in maternal circulation in several species suggests the
      mammary gland as a site of local RLX production. It is unknown whether the
      porcine mammary gland is a source of RLX. Therefore, objectives were to evaluate
      RLX bioactivity in porcine milk during the first 2 weeks of lactation, identify
      the form of RLX in porcine milk, and determine whether mammary tissue from early
      lactation is a source of milk-borne RLX. Milk RLX bioactivity was determined
      using an in vitro bioassay in which cAMP production by human embryonic kidney
      (HEK293T) cells transfected with the human RLX receptor (RXFP1) was measured. RLX
      bioactivity was highest at lactation day (LD) 0, decreasing to undetectable
      levels by LD 4. Immunoblot analysis of milk proteins revealed an 18  kDa band,
      indicating proRLX as the primary form of RLX in porcine milk. ProRLX protein and
      transcripts were detected in porcine mammary tissue on LD 0 and 7. Results
      support the lactocrine hypothesis by defining the nature and a potential source
      for bioactive proRLX in porcine colostrum/milk.

PMID- 21177956
TI  - Reduced progesterone concentration during growth of the first follicular wave
      affects embryo quality but has no effect on embryo survival post transfer in
      lactating dairy cows.
AB  - Fertility of lactating dairy cows is associated with reduced progesterone (P(4))
      concentration compared with nonlactating animals. The objective of the current
      study was to determine whether P(4) during growth of the first follicular wave
      (FFW) affects embryo quality. Lactating Holstein cows at 33+/-3 days post partum
      were allocated to one of three treatments. Cows in the FFW and FFW with P(4)
      (FFWP) treatments started the superstimulation protocol on day 1 of the estrous
      cycle and second follicular wave (SFW) cows started the superstimulation protocol
      on estrous cycle day 7. Cows were superstimulated with 400  mg of NIH-FSH-P1
      (FSH) given twice daily for 5 days, two prostaglandin F(2alpha) (PGF(2alpha))
      injections given with the ninth and tenth injections of FSH, GNRH given 48  h
      after the first PGF(2alpha) injection, and timed insemination 12 and 24  h after
      the GNRH injection. Cows in the FFWP treatment received two intravaginal P(4)
      inserts during the superstimulation. Embryos were recovered 6.5 days after
      artificial insemination and excellent/good and fair embryos were frozen and
      transferred. Blood was sampled daily from estrous cycle day 0 until insemination
      from donor cows. During the superstimulation protocol, P(4) was (P<0.01) greatest
      for SFW cows followed by FFWP and FFW cows respectively. The percentage of
      embryos-oocytes from SFW and FFWP cows classified as excellent/good and fair
      embryos was (P=0.02) greater than those of FFW cows. Pregnancy per embryo
      transfer was not (P>=0.73) affected by embryo donor treatment. Reduced embryo
      quality of cows induced to ovulate the follicles from the first follicular wave
      is a consequence of reduced P(4) during follicle growth.

PMID- 21177957
TI  - Developmental control of the DNA replication and transcription programs.
AB  - Polyploid or polytene cells, which have more than 2C DNA content, are widespread
      throughout nature and present in most differentiated Drosophila tissues. These
      cells also can display differential replication, that is, genomic regions of
      increased or decreased DNA copy number relative to overall genomic ploidy. How
      frequently differential replication is used as a developmental strategy remains
      unclear. Here, we use genome-wide array-based comparative genomic hybridization
      (aCGH) to profile differential DNA replication in isolated and purified larval
      fat body and midgut tissues of Drosophila, and we compare them with recent aCGH
      profiles of the larval salivary gland. We identify sites of euchromatic
      underreplication that are common to all three tissues and others that are tissue
      specific. We demonstrate that both common and tissue-specific underreplicated
      sites are dependent on the Suppressor of Underreplication protein, SUUR. mRNA-seq
      profiling shows that whereas underreplicated regions are generally
      transcriptionally silent in the larval midgut and salivary gland, transcriptional
      silencing and underreplication have been uncoupled in the larval fat body. In
      addition to revealing the prevalence of differential replication, our results
      show that transcriptional silencing and underreplication can be mechanistically
      uncoupled.

PMID- 21177958
TI  - A global analysis of C. elegans trans-splicing.
AB  - Trans-splicing of one of two short leader RNAs, SL1 or SL2, occurs at the 5' ends
      of pre-mRNAs of many C. elegans genes. We have exploited RNA-sequencing data from
      the modENCODE project to analyze the transcriptome of C. elegans for patterns of
      trans-splicing. Transcripts of ~70% of genes are trans-spliced, similar to
      earlier estimates based on analysis of far fewer genes. The mRNAs of most trans
      spliced genes are spliced to either SL1 or SL2, but most genes are not trans
      spliced to both, indicating that SL1 and SL2 trans-splicing use different
      underlying mechanisms. SL2 trans-splicing occurs in order to separate the
      products of genes in operons genome wide. Shorter intercistronic distance is
      associated with greater use of SL2. Finally, increased use of SL1 trans-splicing
      to downstream operon genes can indicate the presence of an extra promoter in the
      intercistronic region, creating what has been termed a "hybrid" operon. Within
      hybrid operons the presence of the two promoters results in the use of the two SL
      classes: Transcription that originates at the promoter upstream of another gene
      creates a polycistronic pre-mRNA that receives SL2, whereas transcription that
      originates at the internal promoter creates transcripts that receive SL1.
      Overall, our data demonstrate that >17% of all C. elegans genes are in operons.

PMID- 21177959
TI  - The Drosophila melanogaster transcriptome by paired-end RNA sequencing.
AB  - RNA-seq was used to generate an extensive map of the Drosophila melanogaster
      transcriptome by broad sampling of 10 developmental stages. In total, 142.2
      million uniquely mapped 64-100-bp paired-end reads were generated on the Illumina
      GA II yielding 356* sequencing coverage. More than 95% of FlyBase genes and 90%
      of splicing junctions were observed. Modifications to 30% of FlyBase gene models
      were made by extension of untranslated regions, inclusion of novel exons, and
      identification of novel splicing events. A total of 319 novel transcripts were
      identified, representing a 2% increase over the current annotation. Alternate
      splicing was observed in 31% of D. melanogaster genes, a 38% increase over
      previous estimations, but significantly less than that observed in higher
      organisms. Much of this splicing is subtle such as tandem alternate splice sites.

PMID- 21177960
TI  - Computational and experimental identification of mirtrons in Drosophila
      melanogaster and Caenorhabditis elegans.
AB  - Mirtrons are intronic hairpin substrates of the dicing machinery that generate
      functional microRNAs. In this study, we describe experimental assays that defined
      the essential requirements for entry of introns into the mirtron pathway. These
      data informed a bioinformatic screen that effectively identified functional
      mirtrons from the Drosophila melanogaster transcriptome. These included 17 known
      and six confident novel mirtrons among the top 51 candidates, and additional
      candidates had limited read evidence in available small RNA data. Our
      computational model also proved effective on Caenorhabditis elegans, for which
      the identification of 14 cloned mirtrons among the top 22 candidates more than
      tripled the number of validated mirtrons in this species. A few low-scoring
      introns generated mirtron-like read patterns from atypical RNA structures, but
      their paucity suggests that relatively few such loci were not captured by our
      model. Unexpectedly, we uncovered examples of clustered mirtrons in both fly and
      worm genomes, including a <8-kb region in C. elegans harboring eight distinct
      mirtrons. Altogether, we demonstrate that discovery of functional mirtrons,
      unlike canonical miRNAs, is amenable to computational methods independent of
      evolutionary constraint.

PMID- 21177961
TI  - Genome-wide analysis of promoter architecture in Drosophila melanogaster.
AB  - Core promoters are critical regions for gene regulation in higher eukaryotes.
      However, the boundaries of promoter regions, the relative rates of initiation at
      the transcription start sites (TSSs) distributed within them, and the functional
      significance of promoter architecture remain poorly understood. We produced a
      high-resolution map of promoters active in the Drosophila melanogaster embryo by
      integrating data from three independent and complementary methods: 21 million cap
      analysis of gene expression (CAGE) tags, 1.2 million RNA ligase mediated rapid
      amplification of cDNA ends (RLM-RACE) reads, and 50,000 cap-trapped expressed
      sequence tags (ESTs). We defined 12,454 promoters of 8037 genes. Our analysis
      indicates that, due to non-promoter-associated RNA background signal, previous
      studies have likely overestimated the number of promoter-associated CAGE clusters
      by fivefold. We show that TSS distributions form a complex continuum of shapes,
      and that promoters active in the embryo and adult have highly similar shapes in
      95% of cases. This suggests that these distributions are generally determined by
      static elements such as local DNA sequence and are not modulated by dynamic
      signals such as histone modifications. Transcription factor binding motifs are
      differentially enriched as a function of promoter shape, and peaked promoter
      shape is correlated with both temporal and spatial regulation of gene expression.
      Our results contribute to the emerging view that core promoters are functionally
      diverse and control patterning of gene expression in Drosophila and mammals.

PMID- 21177962
TI  - The transcriptional diversity of 25 Drosophila cell lines.
AB  - Drosophila melanogaster cell lines are important resources for cell biologists.
      Here, we catalog the expression of exons, genes, and unannotated transcriptional
      signals for 25 lines. Unannotated transcription is substantial (typically 19% of
      euchromatic signal). Conservatively, we identify 1405 novel transcribed regions;
      684 of these appear to be new exons of neighboring, often distant, genes. Sixty
      four percent of genes are expressed detectably in at least one line, but only 21%
      are detected in all lines. Each cell line expresses, on average, 5885 genes,
      including a common set of 3109. Expression levels vary over several orders of
      magnitude. Major signaling pathways are well represented: most differentiation
      pathways are "off" and survival/growth pathways "on." Roughly 50% of the genes
      expressed by each line are not part of the common set, and these show
      considerable individuality. Thirty-one percent are expressed at a higher level in
      at least one cell line than in any single developmental stage, suggesting that
      each line is enriched for genes characteristic of small sets of cells. Most
      remarkable is that imaginal disc-derived lines can generally be assigned, on the
      basis of expression, to small territories within developing discs. These mappings
      reveal unexpected stability of even fine-grained spatial determination. No two
      cell lines show identical transcription factor expression. We conclude that each
      line has retained features of an individual founder cell superimposed on a common
      "cell line" gene expression pattern.

PMID- 21177963
TI  - Diverse transcription factor binding features revealed by genome-wide ChIP-seq in
      C. elegans.
AB  - Regulation of gene expression by sequence-specific transcription factors is
      central to developmental programs and depends on the binding of transcription
      factors with target sites in the genome. To date, most such analyses in
      Caenorhabditis elegans have focused on the interactions between a single
      transcription factor with one or a few select target genes. As part of the
      modENCODE Consortium, we have used chromatin immunoprecipitation coupled with
      high-throughput DNA sequencing (ChIP-seq) to determine the genome-wide binding
      sites of 22 transcription factors (ALR-1, BLMP-1, CEH-14, CEH-30, EGL-27, EGL-5,
      ELT-3, EOR-1, GEI-11, HLH-1, LIN-11, LIN-13, LIN-15B, LIN-39, MAB-5, MDL-1, MEP
      1, PES-1, PHA-4, PQM-1, SKN-1, and UNC-130) at diverse developmental stages. For
      each factor we determined candidate gene targets, both coding and non-coding. The
      typical binding sites of almost all factors are within a few hundred nucleotides
      of the transcript start site. Most factors target a mixture of coding and non
      coding target genes, although one factor preferentially binds to non-coding RNA
      genes. We built a regulatory network among the 22 factors to determine their
      functional relationships to each other and found that some factors appear to act
      preferentially as regulators and others as target genes. Examination of the
      binding targets of three related HOX factors--LIN-39, MAB-5, and EGL-5--indicates
      that these factors regulate genes involved in cellular migration, neuronal
      function, and vulval differentiation, consistent with their known roles in these
      developmental processes. Ultimately, the comprehensive mapping of transcription
      factor binding sites will identify features of transcriptional networks that
      regulate C. elegans developmental processes.

PMID- 21177964
TI  - Broad chromosomal domains of histone modification patterns in C. elegans.
AB  - Chromatin immunoprecipitation identifies specific interactions between genomic
      DNA and proteins, advancing our understanding of gene-level and chromosome-level
      regulation. Based on chromatin immunoprecipitation experiments using validated
      antibodies, we define the genome-wide distributions of 19 histone modifications,
      one histone variant, and eight chromatin-associated proteins in Caenorhabditis
      elegans embryos and L3 larvae. Cluster analysis identified five groups of
      chromatin marks with shared features: Two groups correlate with gene repression,
      two with gene activation, and one with the X chromosome. The X chromosome
      displays numerous unique properties, including enrichment of monomethylated H4K20
      and H3K27, which correlate with the different repressive mechanisms that operate
      in somatic tissues and germ cells, respectively. The data also revealed striking
      differences in chromatin composition between the autosomes and between chromosome
      arms and centers. Chromosomes I and III are globally enriched for marks of active
      genes, consistent with containing more highly expressed genes, compared to
      chromosomes II, IV, and especially V. Consistent with the absence of cytological
      heterochromatin and the holocentric nature of C. elegans chromosomes, markers of
      heterochromatin such as H3K9 methylation are not concentrated at a single region
      on each chromosome. Instead, H3K9 methylation is enriched on chromosome arms,
      coincident with zones of elevated meiotic recombination. Active genes in
      chromosome arms and centers have very similar histone mark distributions,
      suggesting that active domains in the arms are interspersed with heterochromatin
      like structure. These data, which confirm and extend previous studies, allow for
      in-depth analysis of the organization and deployment of the C. elegans genome
      during development.

PMID- 21177965
TI  - Multimodal RNA-seq using single-strand, double-strand, and CircLigase-based
      capture yields a refined and extended description of the C. elegans
      transcriptome.
AB  - We have used a combination of three high-throughput RNA capture and sequencing
      methods to refine and augment the transcriptome map of a well-studied genetic
      model, Caenorhabditis elegans. The three methods include a standard (non
      directional) library preparation protocol relying on cDNA priming and foldback
      that has been used in several previous studies for transcriptome characterization
      in this species, and two directional protocols, one involving direct capture of
      single-stranded RNA fragments and one involving circular-template PCR
      (CircLigase). We find that each RNA-seq approach shows specific limitations and
      biases, with the application of multiple methods providing a more complete map
      than was obtained from any single method. Of particular note in the analysis were
      substantial advantages of CircLigase-based and ssRNA-based capture for defining
      sequences and structures of the precise 5' ends (which were lost using the double
      strand cDNA capture method). Of the three methods, ssRNA capture was most
      effective in defining sequences to the poly(A) junction. Using data sets from a
      spectrum of C. elegans strains and stages and the UCSC Genome Browser, we provide
      a series of tools, which facilitate rapid visualization and assignment of gene
      structures.

PMID- 21177966
TI  - High nucleosome occupancy is encoded at X-linked gene promoters in C. elegans.
AB  - We mapped nucleosome occupancy by paired-end Illumina sequencing in C. elegans
      embryonic cells, adult somatic cells, and a mix of adult somatic and germ cells.
      In all three samples, the nucleosome occupancy of gene promoters on the X
      chromosome differed from autosomal promoters. While both X and autosomal
      promoters exhibit a typical nucleosome-depleted region upstream of transcript
      start sites and a well-positioned +1 nucleosome, X-linked gene promoters on
      average exhibit higher nucleosome occupancy relative to autosomal promoters. We
      show that the difference between X and autosomes does not depend on the somatic
      dosage compensation machinery. Instead, the chromatin difference at promoters is
      partly encoded by DNA sequence, because a model trained on nucleosome sequence
      preferences from S. cerevisiae in vitro data recapitulate nearly completely the
      experimentally observed difference between X and autosomal promoters. The model
      predictions also correlate very well with experimentally determined occupancy
      values genome-wide. The nucleosome occupancy differences observed on X promoters
      may bear on mechanisms of X chromosome dosage compensation in the soma, and
      chromosome-wide repression of X in the germline.

PMID- 21177967
TI  - A spatial and temporal map of C. elegans gene expression.
AB  - The C. elegans genome has been completely sequenced, and the developmental
      anatomy of this model organism is described at single-cell resolution. Here we
      utilize strategies that exploit this precisely defined architecture to link gene
      expression to cell type. We obtained RNAs from specific cells and from each
      developmental stage using tissue-specific promoters to mark cells for isolation
      by FACS or for mRNA extraction by the mRNA-tagging method. We then generated gene
      expression profiles of more than 30 different cells and developmental stages
      using tiling arrays. Machine-learning-based analysis detected transcripts
      corresponding to established gene models and revealed novel transcriptionally
      active regions (TARs) in noncoding domains that comprise at least 10% of the
      total C. elegans genome. Our results show that about 75% of transcripts with
      detectable expression are differentially expressed among developmental stages and
      across cell types. Examination of known tissue- and cell-specific transcripts
      validates these data sets and suggests that newly identified TARs may exercise
      cell-specific functions. Additionally, we used self-organizing maps to define
      groups of coregulated transcripts and applied regulatory element analysis to
      identify known transcription factor- and miRNA-binding sites, as well as novel
      motifs that likely function to control subsets of these genes. By using cell
      specific, whole-genome profiling strategies, we have detected a large number of
      novel transcripts and produced high-resolution gene expression maps that provide
      a basis for establishing the roles of individual genes in cellular
      differentiation.

PMID- 21177968
TI  - Genome-wide analysis of alternative splicing in Caenorhabditis elegans.
AB  - Alternative splicing (AS) plays a crucial role in the diversification of gene
      function and regulation. Consequently, the systematic identification and
      characterization of temporally regulated splice variants is of critical
      importance to understanding animal development. We have used high-throughput RNA
      sequencing and microarray profiling to analyze AS in C. elegans across various
      stages of development. This analysis identified thousands of novel splicing
      events, including hundreds of developmentally regulated AS events. To make these
      data easily accessible and informative, we constructed the C. elegans Splice
      Browser, a web resource in which researchers can mine AS events of interest and
      retrieve information about their relative levels and regulation across
      development. The data presented in this study, along with the Splice Browser,
      provide the most comprehensive set of annotated splice variants in C. elegans to
      date, and are therefore expected to facilitate focused, high resolution in vivo
      functional assays of AS function.

PMID- 21177969
TI  - Deep annotation of Drosophila melanogaster microRNAs yields insights into their
      processing, modification, and emergence.
AB  - Since the initial annotation of miRNAs from cloned short RNAs by the Ambros,
      Tuschl, and Bartel groups in 2001, more than a hundred studies have sought to
      identify additional miRNAs in various species. We report here a meta-analysis of
      short RNA data from Drosophila melanogaster, aggregating published libraries with
      76 data sets that we generated for the modENCODE project. In total, we began with
      more than 1 billion raw reads from 187 libraries comprising diverse developmental
      stages, specific tissue- and cell-types, mutant conditions, and/or Argonaute
      immunoprecipitations. We elucidated several features of known miRNA loci,
      including multiple phased byproducts of cropping and dicing, abundant alternative
      5' termini of certain miRNAs, frequent 3' untemplated additions, and potential
      editing events. We also identified 49 novel genomic locations of miRNA
      production, and 61 additional candidate loci with limited evidence for miRNA
      biogenesis. Although these loci broaden the Drosophila miRNA catalog, this work
      supports the notion that a restricted set of cellular transcripts is competent to
      be specifically processed by the Drosha/Dicer-1 pathway. Unexpectedly, we
      detected miRNA production from coding and untranslated regions of mRNAs and found
      the phenomenon of miRNA production from the antisense strand of known loci to be
      common. Altogether, this study lays a comprehensive foundation for the study of
      miRNA diversity and evolution in a complex animal model.

PMID- 21177970
TI  - Polycomb preferentially targets stalled promoters of coding and noncoding
      transcripts.
AB  - The Polycomb group (PcG) and Trithorax group (TrxG) of proteins are required for
      stable and heritable maintenance of repressed and active gene expression states.
      Their antagonistic function on gene control, repression for PcG and activity for
      TrxG, is mediated by binding to chromatin and subsequent epigenetic modification
      of target loci. Despite our broad knowledge about composition and enzymatic
      activities of the protein complexes involved, our understanding still lacks
      important mechanistic detail and a comprehensive view on target genes. In this
      study we use an extensive data set of ChIP-seq, RNA-seq, and genome-wide
      detection of transcription start sites (TSSs) to identify and analyze thousands
      of binding sites for the PcG proteins and Trithorax from a Drosophila S2 cell
      line. In addition of finding a preference for stalled promoter regions of
      annotated genes, we uncover many intergenic PcG binding sites coinciding with
      nonannotated TSSs. Interestingly, this set includes previously unknown promoters
      for primary transcripts of microRNA genes, thereby expanding the scope of
      Polycomb control to noncoding RNAs essential for development, apoptosis, and
      growth.

PMID- 21177971
TI  - Prediction and characterization of noncoding RNAs in C. elegans by integrating
      conservation, secondary structure, and high-throughput sequencing and array data.
AB  - We present an integrative machine learning method, incRNA, for whole-genome
      identification of noncoding RNAs (ncRNAs). It combines a large amount of
      expression data, RNA secondary-structure stability, and evolutionary conservation
      at the protein and nucleic-acid level. Using the incRNA model and data from the
      modENCODE consortium, we are able to separate known C. elegans ncRNAs from coding
      sequences and other genomic elements with a high level of accuracy (97% AUC on an
      independent validation set), and find more than 7000 novel ncRNA candidates,
      among which more than 1000 are located in the intergenic regions of C. elegans
      genome. Based on the validation set, we estimate that 91% of the approximately
      7000 novel ncRNA candidates are true positives. We then analyze 15 novel ncRNA
      candidates by RT-PCR, detecting the expression for 14. In addition, we
      characterize the properties of all the novel ncRNA candidates and find that they
      have distinct expression patterns across developmental stages and tend to use
      novel RNA structural families. We also find that they are often targeted by
      specific transcription factors (~59% of intergenic novel ncRNA candidates).
      Overall, our study identifies many new potential ncRNAs in C. elegans and
      provides a method that can be adapted to other organisms.

PMID- 21177972
TI  - Plasticity in patterns of histone modifications and chromosomal proteins in
      Drosophila heterochromatin.
AB  - Eukaryotic genomes are packaged in two basic forms, euchromatin and
      heterochromatin. We have examined the composition and organization of Drosophila
      melanogaster heterochromatin in different cell types using ChIP-array analysis of
      histone modifications and chromosomal proteins. As anticipated, the pericentric
      heterochromatin and chromosome 4 are on average enriched for the "silencing"
      marks H3K9me2, H3K9me3, HP1a, and SU(VAR)3-9, and are generally depleted for
      marks associated with active transcription. The locations of the euchromatin
      heterochromatin borders identified by these marks are similar in animal tissues
      and most cell lines, although the amount of heterochromatin is variable in some
      cell lines. Combinatorial analysis of chromatin patterns reveals distinct
      profiles for euchromatin, pericentric heterochromatin, and the 4th chromosome.
      Both silent and active protein-coding genes in heterochromatin display complex
      patterns of chromosomal proteins and histone modifications; a majority of the
      active genes exhibit both "activation" marks (e.g., H3K4me3 and H3K36me3) and
      "silencing" marks (e.g., H3K9me2 and HP1a). The hallmark of active genes in
      heterochromatic domains appears to be a loss of H3K9 methylation at the
      transcription start site. We also observe complex epigenomic profiles of
      intergenic regions, repeated transposable element (TE) sequences, and genes in
      the heterochromatic extensions. An unexpectedly large fraction of sequences in
      the euchromatic chromosome arms exhibits a heterochromatic chromatin signature,
      which differs in size, position, and impact on gene expression among cell types.
      We conclude that patterns of heterochromatin/euchromatin packaging show greater
      complexity and plasticity than anticipated. This comprehensive analysis provides
      a foundation for future studies of gene activity and chromosomal functions that
      are influenced by or dependent upon heterochromatin.

PMID- 21177973
TI  - Chromatin signatures of the Drosophila replication program.
AB  - DNA replication initiates from thousands of start sites throughout the Drosophila
      genome and must be coordinated with other ongoing nuclear processes such as
      transcription to ensure genetic and epigenetic inheritance. Considerable progress
      has been made toward understanding how chromatin modifications regulate the
      transcription program; in contrast, we know relatively little about the role of
      the chromatin landscape in defining how start sites of DNA replication are
      selected and regulated. Here, we describe the Drosophila replication program in
      the context of the chromatin and transcription landscape for multiple cell lines
      using data generated by the modENCODE consortium. We find that while the cell
      lines exhibit similar replication programs, there are numerous cell line-specific
      differences that correlate with changes in the chromatin architecture. We
      identify chromatin features that are associated with replication timing, early
      origin usage, and ORC binding. Primary sequence, activating chromatin marks, and
      DNA-binding proteins (including chromatin remodelers) contribute in an additive
      manner to specify ORC-binding sites. We also generate accurate and predictive
      models from the chromatin data to describe origin usage and strength between cell
      lines. Multiple activating chromatin modifications contribute to the function and
      relative strength of replication origins, suggesting that the chromatin
      environment does not regulate origins of replication as a simple binary switch,
      but rather acts as a tunable rheostat to regulate replication initiation events.

PMID- 21177975
TI  - Model organisms and human health.

PMID- 21177977
TI  - Genetics. Revealing the dark matter of the genome.

PMID- 21177974
TI  - Identification of functional elements and regulatory circuits by Drosophila
      modENCODE.
AB  - To gain insight into how genomic information is translated into cellular and
      developmental programs, the Drosophila model organism Encyclopedia of DNA
      Elements (modENCODE) project is comprehensively mapping transcripts, histone
      modifications, chromosomal proteins, transcription factors, replication proteins
      and intermediates, and nucleosome properties across a developmental time course
      and in multiple cell lines. We have generated more than 700 data sets and
      discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin
      elements, more than tripling the annotated portion of the Drosophila genome.
      Correlated activity patterns of these elements reveal a functional regulatory
      network, which predicts putative new functions for genes, reveals stage- and
      tissue-specific regulators, and enables gene-expression prediction. Our results
      provide a foundation for directed experimental and computational studies in
      Drosophila and related species and also a model for systematic data integration
      toward comprehensive genomic and functional annotation.

PMID- 21177978
TI  - Executive functions as predictors of math learning disabilities.
AB  - In the past years, an increasing number of studies have investigated executive
      functions as predictors of individual differences in mathematical abilities. The
      present longitudinal study was designed to investigate whether the executive
      functions shifting, inhibition, and working memory differ between low achieving
      and typically achieving children and whether these executive functions can be
      seen as precursors to math learning disabilities in children. Furthermore, the
      predictive value of working memory ability compared to preparatory mathematical
      abilities was examined. Two classifications were made based on (persistent)
      mathematical ability in first and second grade. Repeated measures analyses and
      discriminant analyses were used to investigate which functions predicted group
      membership best. Group differences in performance were found on one inhibition
      and three working memory tasks. The working memory tasks predicted math learning
      disabilities, even over and above the predictive value of preparatory
      mathematical abilities.

PMID- 21177979
TI  - Fatty acid-binding proteins and peribronchial angiogenesis in bronchopulmonary
      dysplasia.
AB  - Inflammation plays a key role in the pathogenesis of bronchopulmonary dysplasia
      (BPD). Fatty acid-binding proteins (FABPs) 4 and 5 regulate the inflammatory
      activity of macrophages. Whether FABPs 4 and 5 could play a role in the
      pathogenesis of BPD via the promotion of macrophage inflammatory activity is
      unknown. This study sought to examine whether the expression levels of FABP4 and
      FABP5 were altered in bronchoalveolar lavage fluid and lung tissue in a baboon
      model of BPD. This study also sought to characterize the cell types that express
      these proteins. Real-time PCR, immunoblotting, immunohistochemistry, and double
      immunofluorescence were used to examine the expression of FABPs in samples of
      BPD. Morphometric analysis was used to quantify FABP4-positive peribronchial
      blood vessels in lung sections. FABP4 was primarily expressed in macrophages in
      samples of BPD. In addition, FABP4 was expressed in the endothelial cells of
      blood vessels in peribronchial areas and the vasa vasorum, but not in the
      alveolar vasculature in samples of BPD. FABP4 concentrations were significantly
      increased in lungs and bronchoalveolar lavage fluid samples with BPD. An
      increased density of FABP4-positive peribronchial blood vessels was evident in
      both baboon and human BPD sections. FABP5 was expressed in several cell types,
      including alveolar epithelial cells and macrophages. FABP5 concentrations did not
      show any significant alterations in BPD. In conclusion, FABP4 but not FABP5
      levels are increased in BPD. FABP4 is differentially expressed in endothelial
      cells of the bronchial microvasculature, which demonstrates a previously
      unrecognized expansion in BPD.

PMID- 21177980
TI  - Dendritic cell depletion and repopulation in the lung after irradiation and bone
      marrow transplantation in mice.
AB  - Dendritic cells (DCs) are essential for innate and adaptive immunity, but are
      purported to exhibit variable radiosensitivity in response to irradiation in
      various bone marrow transplantation (BMT) protocols. To address this controversy,
      we analyzed the magnitude of depletion and repopulation of both lung CD11b(pos)
      DC and CD103(pos) DC subsets in response to irradiation and BMT in a murine
      model. In our study, CD45.2(pos) donor bone marrow cells were transplanted into
      irradiated CD45.1(pos) recipient mice to examine the depletion of recipient DC
      subsets and the repopulation of donor DC subsets. We observed an apoptosis
      mediated and necrosis-mediated depletion (> 90%) of the recipient CD103(pos) DC
      subset, and only a 50-60% depletion of recipient CD11b(pos) DCs from lung
      parenchymal tissue on Days 3 and 5, whereas recipient alveolar and lung
      macrophages were much less radiosensitive, showing an approximately 50% depletion
      by Days 14-21 after treatment. A repopulation of lung tissue with donor DC
      subsets had occurred by Days 10 and 28 for CD11b(pos) DCs and CD103(pos) DCs,
      whereas alveolar and lung macrophages were repopulated by 6 and 10 weeks after
      treatment. Furthermore, the infection of mice with Streptococcus pneumoniae
      further accelerated the turnover of lung DCs and lung macrophage subsets. Our
      data illustrate the vulnerability of lung CD103(pos) DCs and CD11b(pos) DCs to
      irradiation, and indicate that an accelerated turnover of lung DC subsets occurs,
      relative to pulmonary and lung macrophages. Our findings may have important
      implications in the development of adjuvant immune-stimulatory protocols that
      could reduce the risk of opportunistic infections in patients undergoing BMT.

PMID- 21177976
TI  - Integrative analysis of the Caenorhabditis elegans genome by the modENCODE
      project.
AB  - We systematically generated large-scale data sets to improve genome annotation
      for the nematode Caenorhabditis elegans, a key model organism. These data sets
      include transcriptome profiling across a developmental time course, genome-wide
      identification of transcription factor-binding sites, and maps of chromatin
      organization. From this, we created more complete and accurate gene models,
      including alternative splice forms and candidate noncoding RNAs. We constructed
      hierarchical networks of transcription factor-binding and microRNA interactions
      and discovered chromosomal locations bound by an unusually large number of
      transcription factors. Different patterns of chromatin composition and histone
      modification were revealed between chromosome arms and centers, with similarly
      prominent differences between autosomes and the X chromosome. Integrating data
      types, we built statistical models relating chromatin, transcription factor
      binding, and gene expression. Overall, our analyses ascribed putative functions
      to most of the conserved genome.

PMID- 21177982
TI  - Wound healing after trauma may predispose to lung cancer metastasis: review of
      potential mechanisms.
AB  - Inflammatory oncotaxis, the phenomenon in which mechanically injured tissues are
      predisposed to cancer metastases, has been reported for a number of tumor types,
      but not previously for histologically proven lung cancer. We review clinical and
      experimental evidence and mechanisms that may underlie inflammatory oncotaxis,
      and provide illustrative examples of two patients with squamous cell carcinoma of
      the lung who developed distant, localized metastatic disease at sites of recent
      physical trauma. Trauma may predispose to metastasis through two distinct, but
      not mutually exclusive, mechanisms: (1) physical trauma induces tissue damage and
      local inflammation, creating a favorable environment that is permissive for
      seeding of metastatic cells from distant sites; and/or (2) micrometastatic foci
      are already present at the time of physical injury, and trauma initiates changes
      in the microenvironment that stimulate the proliferation of the metastatic cells.
      Further exploration of post-traumatic inflammatory oncotaxis may elucidate
      fundamental mechanisms of metastasis and could provide novel strategies to
      prevent cancer metastasis.

PMID- 21177981
TI  - Lys-des[Arg9]-bradykinin alters migration and production of interleukin-12 in
      monocyte-derived dendritic cells.
AB  - This study tested the hypothesis that proinflammatory kinin peptides are involved
      in modulating human dendritic cell (DC) function. Inflammation is accompanied by
      an increased maturation of DCs and the generation of kinins, particularly Lys
      des[Arg(9)]-bradykinin (Lda-BK). We assessed the role of Lda-BK in the activation
      and migration of human monocyte-derived DCs (hMo-DCs) matured through the use of
      LPS, TNF-alpha + IL-1beta, or CD40 ligand. Kinin B(1) and B(2) receptor mRNA and
      protein expression were assessed by confocal microscopy, flow cytometry, and RT
      PCR. The effects of Lda-BK on the migration of mature hMo-DCs were assessed in
      Transwell chambers, whereas the expression of costimulatory molecules and the
      secretion of IL-12 were assessed by flow cytometry and ELISA, respectively. The
      expression of the kinin B(1) receptor (B(1)R) was down-regulated during the
      maturation of hMo-DCs, whereas the expression of B(2)R was unchanged. The B(1)R
      agonist Lda-BK was not chemotactic for hMo-DCs matured using LPS, TNF-alpha + IL
      1beta, or CD40 ligand, but Lda-BK enhanced the secretion of IL-12p70 and
      inhibited the secretion of IL-12p40 by mature hMo-DCs. However, the exposure of
      hMo-DCs matured with TNF-alpha + IL-1beta to Lda-BK for 6 hours decreased
      subsequent migration in response to Lda-BK, the chemokine CCL19, or Lda-BK
      combined with CCL19. The expression of B(1)R was increased in hMo-DCs from
      subjects with asthma compared with subjects without asthma, in keeping with a
      tendency toward increased in vitro migration of asthmatic hMo-DCs in response to
      Lda-BK. The increased formation of Lda-BK and the enhanced expression of B(1)R as
      a consequence of inflammation may alter the migration of mature, antigen-laden
      DCs to regional lymph nodes in response to CCL19, may modulate the secretion of
      cytokines by these DCs, and may contribute to the accumulation of mature DCs in
      the lungs of patients with asthma.

PMID- 21177983
TI  - Glandular gene expression of sinus mucosa in chronic rhinosinusitis with and
      without cystic fibrosis.
AB  - Secretory cells in submucosal glands (SMGs) secrete antibacterial proteins and
      mucin glycoproteins into the apical lumen of the respiratory tract, and these are
      critical for innate immune mucosal integrity. Glandular hyperplasia is manifested
      in diseases with obstructive respiratory pathologies associated with mucous
      hypersecretion, and is predominant in the sinus mucosa of patients with chronic
      rhinosinusitis (CRS), cystic fibrosis (CF), and clinical symptoms of CRS. To gain
      insights into the molecular basis of SMG hyperplasia in CRS, gene expression
      microarray analyses were performed to identify the differences in global and
      specific gene expression in the sinus mucosa of control, CRS, and CRS/CF
      patients. A marked up-regulation of 11 glandular-associated genes in CRS and
      CRS/CF sinus mucosa was evident. The RNA and protein expressions of the four most
      highly up-regulated genes (DSG3, KRT14, PTHLH, and OTX2) were evaluated. An
      increased expression of DSG3, KRT14, and PTHLH was demonstrated at the mRNA and
      protein levels in both CRS and CRS/CF sinus mucosa, whereas the increased
      expression of OTX2 was evident only for CRS/CF sinus mucosa, implicating OTX2 as
      a CF-specific gene. Immunofluorescence analysis localized DSG3, PTHLH, and OTX2
      to serous cells, and KRT14 to myoepithelial cells, in SMGs. Because glandular
      hyperplasia is a central histologic feature of CRS, the identification of
      overexpressed glandular genes in the sinus mucosa lays the groundwork for future
      studies of glandular hyperplasia, and may ultimately lead to the development of
      novel treatments for mucous hypersecretion in patients with CRS.

PMID- 21177984
TI  - In vitro evaluation of potential drug-drug interactions with ticagrelor:
      cytochrome P450 reaction phenotyping, inhibition, induction, and differential
      kinetics.
AB  - Ticagrelor is an orally administered, antiplatelet agent that inhibits the
      prothrombotic effects of ADP on the platelet by antagonizing the P2Y(12)
      receptor. Ticagrelor is a reversibly binding direct-acting P2Y(12) antagonist and
      does not require metabolic activation to achieve its antiplatelet effect. CYP3A4
      and CYP3A5 appear to be the enzymes predominantly responsible for the formation
      of the ticagrelor active and inactive metabolites, AR-C124910XX and AR-C133913XX.
      The apparent K(m) values in human liver microsomes are 27.0 and 38.8 MUM, with
      V(max) values of 730 and 417 pmol/min/mg for AR-C124910XX and AR-C133913XX,
      respectively. Ticagrelor moderately inhibited CYP2C9 activity in human liver
      microsomes with an IC(50) of 10.5 MUM, while exhibiting little or no inhibition
      of CYP1A2, CYP2B6, CYP2C8, CYP2C19, CYP2D6, and CYP2E1. In human liver
      microsomes, ticagrelor inhibited midazolam 4-hydroxylation with an IC(50) of 8.2
      MUM, while activating 1'-hydroxylation of midazolam. Studies with recombinant
      enzymes suggested that cytochrome b(5) and CYP3A4 interactions play a significant
      role in this differential kinetic behavior. Evaluated in fresh human hepatocytes
      at concentration up to 20 MUM, ticagrelor was not an inducer of CYP1A2 or CYP3A4.
      Although ticagrelor exhibited a tendency for CYP2B6 and CYP2C9 induction, its
      potential to cause drug interactions via the induction of these enzymes is low
      when its exposure at a therapeutic dose is considered.

PMID- 21177986
TI  - Metabolism and excretion of asenapine in healthy male subjects.
AB  - The metabolism and excretion of asenapine [(3aRS,12bRS)-5-chloro-2-methyl
      2,3,3a,12b-tetrahydro-1H-dibenzo[2,3:6,7]-oxepino [4,5-c]pyrrole (2Z)-2
      butenedioate (1:1)] were studied after sublingual administration of [(14)C]
      asenapine to healthy male volunteers. Mean total excretion on the basis of the
      percent recovery of the total radioactive dose was ~90%, with ~50% appearing in
      urine and ~40% excreted in feces; asenapine itself was detected only in feces.
      Metabolic profiles were determined in plasma, urine, and feces using high
      performance liquid chromatography with radioactivity detection. Approximately 50%
      of drug-related material in human plasma was identified or quantified. The
      remaining circulating radioactivity corresponded to at least 15 very polar, minor
      peaks (mostly phase II products). Overall, >70% of circulating radioactivity was
      associated with conjugated metabolites. Major metabolic routes were direct
      glucuronidation and N-demethylation. The principal circulating metabolite was
      asenapine N(+)-glucuronide; other circulating metabolites were N
      desmethylasenapine-N-carbamoyl-glucuronide, N-desmethylasenapine, and asenapine
      11-O-sulfate. In addition to the parent compound, asenapine, the principal
      excretory metabolite was asenapine N(+)-glucuronide. Other excretory metabolites
      were N-desmethylasenapine-N-carbamoylglucuronide, 11-hydroxyasenapine followed by
      conjugation, 10,11-dihydroxy-N-desmethylasenapine, 10,11-dihydroxyasenapine
      followed by conjugation (several combinations of these routes were found) and N
      formylasenapine in combination with several hydroxylations, and most probably
      asenapine N-oxide in combination with 10,11-hydroxylations followed by
      conjugations. In conclusion, asenapine was extensively and rapidly metabolized,
      resulting in several regio-isomeric hydroxylated and conjugated metabolites.

PMID- 21177985
TI  - In vitro metabolism of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin in
      human liver microsomes.
AB  - The objective of this study was to investigate the oxidative metabolism pathways
      of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), a
      geldanamycin (GA) derivative and 90-kDa heat shock protein inhibitor. In vitro
      metabolic profiles of 17-DMAG were examined by using pooled human liver
      microsomes (HLMs) and recombinant CYP450 isozymes in the presence or absence of
      reduced GSH. In addition to 17-DMAG hydroquinone and 19-glutathionyl 17-DMAG,
      several oxidative metabolites of 17-DMAG were detected and characterized by
      liquid chromatography-tandem mass spectrometry. Different from previously
      reported primary biotransformations of GA and GA derivatives, 17-DMAG was not
      metabolized primarily through the reduction of benzoquinone and GSH conjugation
      in HLMs. In contrast, the primary biotransformations of 17-DMAG in HLMs were
      hydroxylation and demethylation on its side chains. The most abundant metabolite
      was produced by demethylation from the methoxyl at position 12. The reaction
      phenotyping study showed that CYP3A4 and 3A5 were the major cytochrome P450
      isozymes involved in the oxidative metabolism of 17-DMAG, whereas CYP2C8, 2D6,
      2A6, 2C19, and 1A2 made minor contributions to the formation of metabolites. On
      the basis of the identified metabolite profiles, the biotransformation pathways
      for 17-DMAG in HLMs were proposed.

PMID- 21177987
TI  - Breastfeeding initiation in a rural sample: predictive factors and the role of
      smoking.
AB  - The study objective was to identify demographic, medical, and health behavior
      factors that predict breastfeeding initiation in a rural population with low
      breastfeeding rates. Participants were 2323 women who experienced consecutive
      deliveries at 2 hospitals, with data obtained through detailed chart review. Only
      half the women initiated breastfeeding, which was significantly associated with
      higher levels of education, private insurance, nonsmoking and non-drug-using
      status, and primiparity, after controlling for confounders. Follow-up analyses
      revealed that smoking status was the strongest predictor of failure to
      breastfeed, with nonsmokers nearly twice as likely to breastfeed as smokers and
      with those who had smoked a pack per day or more the least likely to breastfeed.
      Findings reveal many factors placing women at risk for not breastfeeding and
      suggest that intervention efforts should encourage a combination of smoking
      cessation and breastfeeding while emphasizing that breastfeeding is not
      contraindicated even if the mother continues to smoke.

PMID- 21177988
TI  - Knowledge, beliefs, and practices regarding exclusive breastfeeding of infants
      younger than 6 months in Mozambique: a qualitative study.
AB  - Only 37% of infants younger than 6 months in Mozambique are exclusively
      breastfed. A qualitative assessment was undertaken to identify the knowledge,
      beliefs, and practices around exclusive breastfeeding--specifically, those of
      mothers, fathers, grandmothers, and nurses--and to identify the support networks.
      Results show many barriers. In addition to receiving breast milk, infants receive
      water, traditional medicines, and porridges before 6 months of age. Many mothers
      had heard of the recommendation to exclusively breastfeed for 6 months. However,
      other family decision makers had heard less about exclusive breastfeeding, and
      many expressed doubts about its feasibility. Some of them expressed willingness
      to support exclusive breastfeeding if they were informed by health workers.
      Nurses know the benefits of exclusive breastfeeding and pass this information on
      verbally but have insufficient counseling skills. Interventions to improve
      exclusive breastfeeding should target family and community members and include
      training of health workers in counseling to resolve breastfeeding problems.

PMID- 21177989
TI  - The association between women's perceptions of professional support and problems
      experienced on breastfeeding cessation: a Western Australian study.
AB  - A cross-sectional survey was used to determine the association among women's
      breastfeeding problems, their perceptions of support from midwives and child
      health nurses, and breastfeeding cessation in the first 10 weeks postbirth in a
      sample of Western Australian women (N = 2669). Primiparous women (75.8%)
      experienced significantly more problems that multiparous women (52.6%). Although
      78.8% of all women agreed or strongly agreed that staff were helpful with
      feeding, 53.4% confirmed that different midwives offered different feeding
      advice; however, receiving different advice from midwives around feeding was not
      associated with breastfeeding cessation. Differences in breastfeeding cessation
      were associated with parity. Primiparous women's cessation was associated with
      experiencing any breastfeeding problems, unhelpful hospital midwives, and
      unhelpful information from child health nurses, whereas for multiparous women,
      this included 2 or more breastfeeding problems, not being able to choose when to
      feed, and unhelpful information from child health nurses.

PMID- 21177990
TI  - ASSIMILATOR: a new tool to inform selection of associated genetic variants for
      functional studies.
AB  - MOTIVATION: Fine-mapping experiments from genome-wide association studies (GWAS)
      are underway for many complex diseases. These are likely to identify a number of
      putative causal variants, which cannot be separated further in terms of strength
      of genetic association due to linkage disequilibrium. The challenge will be
      selecting which variant to prioritize for subsequent expensive functional
      studies. A wealth of functional information generated from wet lab experiments
      now exists but cannot be easily interrogated by the user. Here, we describe a
      program designed to quickly assimilate this data called ASSIMILATOR and validate
      the method by interrogating two regions to show its effectiveness. AVAILABILITY:
      http://www.medicine.manchester.ac.uk/musculoskeletal/research/arc/genetics/bioinf
      rmatics/assimilator/.

PMID- 21177991
TI  - Role of the vesicular transporter VGLUT3 in retrograde release of glutamate by
      cerebellar Purkinje cells.
AB  - In the cerebellum, retrograde release of glutamate (Glu) by Purkinje cells (PCs)
      participates in the control of presynaptic neurotransmitter release responsible
      for the late component of depolarization-induced suppression of excitation (DSE),
      as well as for depolarization-induced potentiation of inhibition (DPI). It might
      also participate in the depolarization-induced slow current (DISC) in PCs,
      although this contribution was later challenged. We also know that both DPI and
      DISC are soluble N-ethylmaleimide-sensitive factor attachment protein receptor
      (SNARE)-dependent processes, although the molecular nature of the vesicular
      transporter was not determined. In PCs, VGLUT3 is the only known vesicular
      glutamate transporter identified and is expressed during the same developmental
      frame as when DPI, DISC, and the Glu-dependent component of DSE are observed. We
      therefore tested the hypothesis that all these processes depend on the presence
      of VGLUT3 by comparing the Glu-dependent component of DSE, DPI, and DISC in
      nearly mature (2- to 3-wk-old) wild-type and VGLUT3 knockout mice. Our data
      demonstrate that, in nearly mature mice, the slow component of DSE occurs through
      vesicular release of Glu that involves VGLUT3. This Glu-dependent component of
      DSE is no longer present in fully mature mice. This study also establishes that,
      in nearly mature mice, DPI also depends on the presence of VGLUT3, whereas this
      is not the case for DISC. Finally, the unusually large basal paired-pulse
      facilitation observed in nearly mature VGLUT3(-/-) mice but not in adult ones
      suggests that some basal retrograde release of Glu occurs during development and
      contributes to basal concentrations of extracellular Glu.

PMID- 21177992
TI  - Reversal of the late phase of spike frequency adaptation in cat spinal
      motoneurons during fictive locomotion.
AB  - In spinal motoneurons, late spike frequency adaptation (SFA) is defined as the
      slowing of the firing rate over tens of seconds and can be seen during sustained
      or intermittent current injection. Although the function of late SFA is not
      known, it may result in a decrease in force production over time, or muscle
      fatigue. Because locomotion can persist for long periods of time without fatigue,
      late SFA was studied using intracellular recordings from adult cat motoneurons
      during fictive locomotion. Of eight lumbar motoneurons studied, all showed late
      adaptation during control conditions, but none demonstrated late adaptation
      during locomotor activity. The most consistent properties that correlated with
      the presence or absence of late SFA were those related to availability of fast,
      inactivating sodium channels, particularly action potential rate of rise.
      Evidence of the reversal of late SFA during locomotion was present for several
      minutes following locomotor trials, consistent with the suggestion that SFA is
      modulated through slow metabotropic pathways. The abolition of late adaptation in
      spinal motoneurons during fictive locomotion is an example of a state-dependent
      change in the "intrinsic" properties of mammalian motoneurons. This change
      contributes to increased excitability of motoneurons during locomotion and
      results in robust firing during sustained locomotion.

PMID- 21177994
TI  - Time course of the induction of homeostatic plasticity generated by repeated
      transcranial direct current stimulation of the human motor cortex.
AB  - Several mechanisms have been proposed that control the amount of plasticity in
      neuronal circuits and guarantee dynamic stability of neuronal networks.
      Homeostatic plasticity suggests that the ease with which a synaptic connection is
      facilitated/suppressed depends on the previous amount of network activity. We
      describe how such homeostatic-like interactions depend on the time interval
      between two conditioning protocols and on the duration of the preconditioning
      protocol. We used transcranial direct current stimulation (tDCS) to produce short
      lasting plasticity in the motor cortex of healthy humans. In the main experiment,
      we compared the aftereffect of a single 5-min session of anodal or cathodal tDCS
      with the effect of a 5-min tDCS session preceded by an identical 5-min
      conditioning session administered 30, 3, or 0 min beforehand. Five-minute anodal
      tDCS increases excitability for about 5 min. The same duration of cathodal tDCS
      reduces excitability. Increasing the duration of tDCS to 10 min prolongs the
      duration of the effects. If two 5-min periods of tDCS are applied with a 30-min
      break between them, the effect of the second period of tDCS is identical to that
      of 5-min stimulation alone. If the break is only 3 min, then the second session
      has the opposite effect to 5-min tDCS given alone. Control experiments show that
      these shifts in the direction of plasticity evolve during the 10 min after the
      first tDCS session and depend on the duration of the first tDCS but not on
      intracortical inhibition and facilitation. The results are compatible with a time
      dependent "homeostatic-like" rule governing the response of the human motor
      cortex to plasticity probing protocols.

PMID- 21177993
TI  - Alterations of action potentials and the localization of Nav1.6 sodium channels
      in spared axons after hemisection injury of the spinal cord in adult rats.
AB  - Previously, we reported a pronounced reduction in transmission through surviving
      axons contralateral to chronic hemisection (HX) of adult rat spinal cord. To
      examine the cellular and molecular mechanisms responsible for this diminished
      transmission, we recorded intracellularly from lumbar lateral white matter axons
      in deeply anesthetized adult rats in vivo and measured the propagation of action
      potentials (APs) through rubrospinal/reticulospinal tract (RST/RtST) axons
      contralateral to chronic HX at T10. We found decreased excitability in these
      axons, manifested by an increased rheobase to trigger APs and longer latency for
      AP propagation passing the injury level, without significant differences in
      axonal resting membrane potential and input resistance. These
      electrophysiological changes were associated with altered spatial localization of
      Nav1.6 sodium channels along axons: a subset of axons contralateral to the injury
      exhibited a diffuse localization (>10 MUm spread) of Nav1.6 channels, a pattern
      characteristic of demyelinated axons (Craner MJ, Newcombe J, Black JA, Hartle C,
      Cuzner ML, Waxman SG. Proc Natl Acad Sci USA 101: 8168-8173, 2004b). This result
      was substantiated by ultrastructural changes seen with electron microscopy, in
      which an increased number of large-caliber, demyelinated RST axons were found
      contralateral to the chronic HX. Therefore, an increased rheobase, pathological
      changes in the distribution of Nav1.6 sodium channels, and the demyelination of
      contralateral RST axons are likely responsible for their decreased conduction
      chronically after HX and thus may provide novel targets for strategies to improve
      function following incomplete spinal cord injury.

PMID- 21177995
TI  - Spatial summation in macaque parietal area 7a follows a winner-take-all rule.
AB  - While neurons in posterior parietal cortex have been found to signal the presence
      of a salient stimulus among multiple items in a display, spatial summation within
      their receptive field in the absence of an attentional bias has never been
      investigated. This information, however, is indispensable when one investigates
      the mechanisms of spatial attention and competition between multiple visual
      objects. To examine the spatial summation rule in parietal area 7a neurons, we
      trained rhesus monkeys to fixate on a central cross while two identical stimuli
      were briefly displayed in a neuron's receptive field. The response to a pair of
      dots was compared with the responses to the same dots when they were presented
      individually. The scaling and power parameters of a generalized summation
      algorithm varied greatly, both across neurons and across combinations of stimulus
      locations. However, the averaged response of the recorded population of 7a
      neurons was consistent with a winner-take-all rule for spatial summation. A
      control experiment where a monkey covertly attended to both stimuli
      simultaneously suggests that attention introduces additional competition by
      facilitating the less optimal stimulus. Thus an averaging stage is introduced
      between ~ 200 and 300 ms of the response to a pair of stimuli. In short, the
      summation algorithm over the population of area 7a neurons carries the signature
      of a winner-take-all operation, with spatial attention possibly influencing the
      temporal dynamics of stimulus competition, that is the moment that the "winner"
      takes "victory" over the "loser" stimulus.

PMID- 21177996
TI  - Activation of subthalamic neurons by contralateral subthalamic deep brain
      stimulation in Parkinson disease.
AB  - Multiple studies have shown bilateral improvement in motor symptoms in Parkinson
      disease (PD) following unilateral deep brain stimulation (DBS) of the subthalamic
      nucleus (STN) and internal segment of the globus pallidus, yet the mechanism(s)
      underlying this phenomenon are poorly understood. We hypothesized that STN
      neuronal activity is altered by contralateral STN DBS. This hypothesis was tested
      intraoperatively in humans with advanced PD using microelectrode recordings of
      the STN during contralateral STN DBS. We demonstrate alterations in the discharge
      pattern of STN neurons in response to contralateral STN DBS including short
      latency, temporally precise, stimulation frequency-independent responses
      consistent with antidromic activation. Furthermore, the total discharge frequency
      during contralateral high frequency stimulation (160 Hz) was greater than during
      low frequency stimulation (30 Hz) and the resting state. These findings
      demonstrate complex responses to DBS and imply that output activation throughout
      the basal ganglia-thalamic-cortical network rather than local inhibition is a
      therapeutic mechanism of DBS.

PMID- 21177998
TI  - Modulation of synaptic transmission from primary afferents to spinal substantia
      gelatinosa neurons by group III mGluRs in GAD65-EGFP transgenic mice.
AB  - Group III metabotropic glutamate receptors (mGluRs) are involved in nociceptive
      transmission in the spinal cord. However, the cellular mechanism underlying the
      modulation of synaptic transmission from nociceptive primary afferents to dorsal
      horn neurons by group III mGluRs has yet to be explored. In this study, we used
      transgenic mice expressing enhanced green fluorescent protein (EGFP) under the
      control of the glutamate decarboxylase (GAD) 65 promoter to identify specific
      subpopulations of GABAergic inhibitory interneurons. By GABA immunolabeling, we
      confirmed the majority of GAD65-EGFP-expressing neurons were GABAergic. Because
      GAD65-EGFP-expressing neurons have not been examined in detail before, we first
      investigated the physiological properties of GAD65-EGFP- and non-EGFP-expressing
      neurons in substantia gelatinosa (SG) of the spinal dorsal horn. Membrane
      properties, such as the resting membrane potential, membrane capacitance, action
      potential threshold, and action potential height, differed significantly between
      these two groups of neurons. Most EGFP-expressing neurons displayed a tonic
      firing pattern (73% of recorded neurons) and received monosynaptic Adelta and/or
      C primary afferent inputs (85% of recorded neurons). In contrast, we observed a
      delayed firing pattern in 53% of non-EGFP-expressing neurons. After identifying
      the physiological properties of EGFP-expressing neurons, we tested the effects of
      group III mGluRs on synaptic transmission pharmacologically. A group III mGluR
      agonist, L-AP4, attenuated Adelta fiber-evoked synaptic transmission but did not
      affect C fiber-evoked synaptic transmission to EGFP-expressing neurons. Similar
      primary afferent-specific inhibition by L-AP4 was also observed in non-EGFP
      expressing neurons. Moreover, Adelta fiber-evoked synaptic transmission was
      suppressed by a selective mGluR7 agonist, AMN082. These results suggest that
      modulation of the synaptic transmission from primary afferents to SG neurons by
      group III mGluR agonist is specific to the type of nociceptive primary afferents
      but not to the type of target neurons.

PMID- 21177997
TI  - Endocannabinoids mediate synaptic plasticity at glutamatergic synapses on spiny
      neurons within a basal ganglia nucleus necessary for song learning.
AB  - Activation of type 1 cannabinoid receptors (CB(1)R) in many central nervous
      system structures induces both short- and long-term changes in synaptic
      transmission. Within mammalian striatum, endocannabinoids (eCB) are one of
      several mechanisms that induce synaptic plasticity at glutamatergic terminals
      onto medium spiny neurons. Striatal synaptic plasticity may contribute a critical
      component of adaptive motor coordination and procedural learning. Songbirds are
      advantageous for studying the neural mechanisms of motor learning because they
      possess a neural pathway necessary for song learning and adult song plasticity
      that includes a striato-pallidal nucleus, area X (homologous to a portion of
      mammalian basal ganglia). Recent findings suggest that eCBs contribute to vocal
      development. For example, dense CB(1)R expression in song control nuclei peaks
      around the closure of the sensori-motor integration phase of song development.
      Also, systemic administration of a CB(1)R agonist during vocal development
      impairs song learning. Here we test whether activation of CB(1)R alters
      excitatory synaptic input on spiny neurons in area X of adult male zebra finches.
      Application of the CB(1)R agonist WIN55212-2 decreased excitatory postsynaptic
      current (EPSC) amplitude; that decrease was blocked by the CB(1)R antagonist
      AM251. Guided by eCB experiments in mammalian striatum, we tested and verified
      that at least two mechanisms indirectly activate CB(1)Rs through eCBs in area X.
      First, activation of group I metabotropic glutamate receptors with the agonist
      3,5-dihydroxyphenylglycine (DHPG) induced a CB(1)R-mediated reduction in EPSC
      amplitude. Second, we observed that a 10 s postsynaptic depolarization induced a
      calcium-mediated, eCB-dependent decrease in synaptic strength that resisted
      rescue with late CB(1)R blockade. Together, these results show that eCB
      modulation occurs at inputs to area X spiny neurons and could influence motor
      learning and production.

PMID- 21177999
TI  - The extent and strength of electrical coupling between inferior olivary neurons
      is heterogeneous.
AB  - Gap junctions constitute the only form of synaptic communication between neurons
      in the inferior olive (IO), which gives rise to the climbing fibers innervating
      the cerebellar cortex. Although its exact functional role remains undetermined,
      electrical coupling was shown to be necessary for the transient formation of
      functional compartments of IO neurons and to underlie the precise timing of
      climbing fibers required for cerebellar learning. So far, most functional
      considerations assume the existence of a network of permanently and homogeneously
      coupled IO neurons. Contrasting this notion, our results indicate that coupling
      within the IO is highly variable. By combining tracer-coupling analysis and
      paired electrophysiological recordings, we found that individual IO neurons could
      be coupled to a highly variable number of neighboring neurons. Furthermore, a
      given neuron could be coupled at remarkably different strengths with each of its
      partners. Freeze-fracture analysis of IO glomeruli revealed the close proximity
      of glutamatergic postsynaptic densities to connexin 36-containing gap junctions,
      at distances comparable to separations between chemical transmitting domains and
      gap junctions in goldfish mixed contacts, where electrical coupling was shown to
      be modulated by the activity of glutamatergic synapses. On the basis of
      structural and molecular similarities with goldfish mixed synapses, we speculate
      that, rather than being hardwired, variations in coupling could result from
      glomerulus-specific long-term modulation of gap junctions. This striking
      heterogeneity of coupling might act to finely influence the synchronization of IO
      neurons, adding an unexpected degree of complexity to olivary networks.

PMID- 21178000
TI  - A novel path for rapid transverse communication of vestibular signals in turtle
      cerebellum.
AB  - Voltage-sensitive dye activity within the thin, unfoliated turtle cerebellar
      cortex (Cb) was recorded in vitro during eighth cranial nerve (nVIII)
      stimulation. Short latency responses were localized to the middle of the lateral
      edges of both ipsilateral and contralateral Cb [vestibulocerebellum (vCb)]. Even
      with a severed contralateral Cb peduncle, stimulation of the nVIII ipsilateral to
      the intact peduncle evoked contralateral vCb responses with a mean latency of
      only 0.25 ms after the ipsilateral responses, even though the distance between
      them was ~ 5 mm. We investigated whether a rapidly conducting commissure exists
      between each vCb by stimulating one of them directly. Responses in both vCb
      spread sagittally, but, surprisingly, there was no sequential activation along a
      transverse Cb beam between them. In contrast, stimulation medial to either vCb
      evoked transverse beams that required ~ 20 ms to cross the Cb. Therefore, the
      rapid commissural connection between each vCb is not mediated by slowly
      conducting parallel fibers. Also, the vCb was not strongly activated by climbing
      fiber stimulation, suggesting that inputs to vCb involve distinct cerebellar
      circuits. Responses between the two vCb remained following knife cuts through the
      rostral and caudal Cb along the midline, through both peduncles, and even shallow
      midline cuts to the middle Cb through its white matter and granule cell layer.
      Commissural responses were still observed only with a narrow transverse bridge
      between each vCb or in thick transverse Cb slices. Horseradish peroxidase
      transport from one vCb labeled transverse axons traveling within the Purkinje
      cell layer that were larger than parallel fibers and lacked varicosities. In
      sagittal sections, cross-section profiles of myelinated axons were observed
      around Purkinje cells midway between the rostral and caudal Cb. This novel
      pathway for transverse communication between lateral edges of turtle Cb suggests
      that afferents may directly conduct vestibular information rapidly across the Cb
      to coordinate vestibulomotor reflex behaviors.

PMID- 21178001
TI  - Somatosensory context alters auditory responses in the cochlear nucleus.
AB  - The cochlear nucleus, the first central auditory structure, performs initial
      stimulus processing and segregation of information into parallel ascending
      pathways. It also receives nonauditory inputs. Here we show in vivo that
      responses of dorsal cochlear nucleus (DCN) principal neurons to sounds can change
      significantly depending on the presence or absence of inputs from the
      somatosensory dorsal column nucleus occurring before the onset of auditory
      stimuli. The effects range from short-term suppression of spikes lasting a few
      milliseconds at the onset of the stimulus to long-term increases or decreases in
      spike rate that last throughout the duration of an acoustic stimulus (up to
      several hundred milliseconds). The long-term effect requires only a single
      electrical stimulus pulse to initiate and seems to be similar to persistent
      activity reported in other parts of the brain. Among the DCN inhibitory
      interneurons, only the cartwheel cells show a long-term rate decrease that could
      account for the rate increases (but not the decreases) of DCN principal cells.
      Thus even at the earliest stages of auditory processing, the represented
      information is dependent on nonauditory context, in this case somatosensory
      events.

PMID- 21178002
TI  - Functional redundancy between thymic CD8alpha+ and Sirpalpha+ conventional
      dendritic cells in presentation of blood-derived lysozyme by MHC class II
      proteins.
AB  - We evaluated the presentation of blood-derived protein Ags by APCs in the thymus.
      Two conventional dendritic cells (cDCs), the CD8alpha(+)Sirpalpha(-)CD11c(hi)
      (CD8alpha(+) cDC) and the CD8alpha(-)Sirpalpha(+)CD11c(hi) (Sirpalpha(+) cDC),
      were previously identified as presenting MHC class II bound peptides from hen egg
      white lysozyme (HEL) injected intravenously. All thymic APCs acquired the
      injected HEL, with the plasmacytoid dendritic cell being the best, followed by
      the Sirpalpha(+) cDC and the CD8alpha(+) cDC. Both cDCs induced to similar extent
      negative selection and regulatory T cells in HEL TCR transgenic mice, indicating
      a redundant role of the two cDC subsets in the presentation of blood-borne HEL.
      Immature dendritic cells or plasmacytoid dendritic cells were considerably less
      efficient. Batf3(-/-) mice, with significantly reduced numbers of CD8alpha(+)
      cDCs, were not impaired in HEL presentation by I-A(k) molecules of thymic APCs.
      Lastly, clodronate liposome treatment of TCR transgenic mice depleted blood APCs
      including Sirpalpha(+) cDCs without affecting the number of thymic APCs. In such
      treated mice, there was no effect on negative selection or regulatory T cells in
      mice when administering HEL, indicating that the T cell responses were mediated
      primarily by the cDCs localized in the thymus.

PMID- 21178003
TI  - Mycobacterium tuberculosis directs immunofocusing of CD8+ T cell responses
      despite vaccination.
AB  - Vaccines that elicit T cell responses try to mimic protective memory T cell
      immunity after infection by increasing the frequency of Ag-specific T cells in
      the immune repertoire. However, the factors that determine immunodominance during
      infection and after vaccination and the relation between immunodominance and
      protection are incompletely understood. We previously identified TB10.4(20-28) as
      an immunodominant epitope recognized by H2-K(d)-restricted CD8(+) T cells after
      M. tuberculosis infection. Here we report a second epitope, EspA(150-158), that
      is recognized by a substantial number of pulmonary CD8(+) T cells. The relative
      abundance of these T cells in the naive repertoire only partially predicts their
      relative frequency after M. tuberculosis infection. Furthermore, although
      vaccination with recombinant vaccinia virus expressing these epitopes changes
      their relative immunodominance in the preinfection T cell repertoire, this change
      is transient after challenge with M. tuberculosis. We speculate that factors
      intrinsic to the chronic nature of M. tuberculosis infection establishes the
      hierarchy of immunodominance and may explain the failure of some vaccines to
      provide protection.

PMID- 21178004
TI  - IFN regulatory factor 8 restricts the size of the marginal zone and follicular B
      cell pools.
AB  - Transcriptional control of marginal zone (MZ) and follicular (FO) B cell
      development remains incompletely understood. The transcription factor, IFN
      regulatory factor (IRF)8, is known to play important roles in the differentiation
      of early B cells. In this article, we demonstrate that IRF8 is also required for
      normal development of MZ and FO B cells. Mice with a conventional knockout of
      Irf8 (IRF8(-/-)) or a point mutation in the IRF association domain of IRF8 had
      increased numbers of MZ B cells. To determine the B cell-intrinsic effects of
      IRF8 deficiency, we generated mice with a conditional allele of Irf8 crossed with
      CD19-Cre mice (designated IRF8-conditional knockout [CKO]). These mice had
      enlarged MZ and increased numbers of MZ and FO B cells compared with controls.
      The FO B cells of CKO mice exhibited reduced expression of CD23 and moderately
      increased expression of CD21. Gene-expression profiling showed that increased B
      cell production in IRF8-CKO mice was associated with changes in expression of
      genes involved in regulation of transcription, signaling, and inflammation.
      Functional studies showed that IRF8-CKO mice generated normal Ab responses to T
      independent and T-dependent Ags. Thus, IRF8 controls the expansion and maturation
      of MZ and FO B cells but has little effect on B cell function.

PMID- 21178005
TI  - Tumor-associated a2 vacuolar ATPase acts as a key mediator of cancer-related
      inflammation by inducing pro-tumorigenic properties in monocytes.
AB  - Cancer-related inflammation profoundly affects tumor progression. Tumor
      associated macrophages (TAMs) are known regulators of that inflammation, but the
      factors that initiate cancer-related inflammation are poorly understood. Tumor
      invasiveness and poor clinical outcome are linked to increased expression of cell
      surface-associated vacuolar adenosine triphosphatases. The a2 isoform vacuolar
      adenosine triphosphatase is found on the surface on many solid tumors, and we
      have identified a peptide cleaved from a2 isoform vacuolar adenosine
      triphosphatase called a2NTD. a2NTD has properties necessary to induce monocytes
      into a pro-oncogenic TAM phenotype. The peptide upregulated both pro- and anti
      inflammatory mediators. These included IL-1beta and IL-10, which are important in
      promoting inflammation and immune escape by tumor cells. The secretion of
      inflammatory cytokine IL-1beta was dependent on ATP, K(+) efflux, and reactive
      oxygen species, all mediators that activate the inflammasome. These findings
      describe a mechanism by which tumor cells affect the maturation of TAMs via a
      nontraditional cytokine-like signal, the a2NTD peptide.

PMID- 21178006
TI  - P-Rex1 and Vav1 cooperate in the regulation of formyl-methionyl-leucyl
      phenylalanine-dependent neutrophil responses.
AB  - G protein-coupled receptor (GPCR) activation elicits neutrophil responses such as
      chemotaxis and reactive oxygen species (ROS) formation, which depend on the small
      G protein Rac and are essential for host defense. P-Rex and Vav are two families
      of guanine-nucleotide exchange factors (GEFs) for Rac, which are activated
      through distinct mechanisms but can both control GPCR-dependent neutrophil
      responses. It is currently unknown whether they play specific roles or whether
      they can compensate for each other in controlling these responses. In this study,
      we have assessed the function of neutrophils from mice deficient in P-Rex and/or
      Vav family GEFs. We found that both the P-Rex and the Vav family are important
      for LPS priming of ROS formation, whereas particle-induced ROS responses and cell
      spreading are controlled by the Vav family alone. Surprisingly, fMLF-stimulated
      ROS formation, adhesion, and chemotaxis were synergistically controlled by P-Rex1
      and Vav1. These responses were more severely impaired in neutrophils lacking both
      P-Rex1 and Vav1 than those lacking the entire P-Rex family, the entire Vav
      family, or both P-Rex1 and Vav3. P-Rex1/Vav1 (P1V1) double-deficient cells also
      showed the strongest reduction in fMLF-stimulated activation of Rac1 and Rac2.
      This reduction in Rac activity may be sufficient to cause the defects observed in
      fMLF-stimulated P1V1 neutrophil responses. Additionally, Mac-1 surface expression
      was reduced in P1V1 cells, which might contribute further to defects in responses
      involving integrins, such as GPCR-stimulated adhesion and chemotaxis. We conclude
      that P-Rex1 and Vav1 together are the major fMLFR-dependent Dbl family Rac-GEFs
      in neutrophils and cooperate in the control of fMLF-stimulated neutrophil
      responses.

PMID- 21178007
TI  - TLR 2 and CD14 mediate innate immunity and lung inflammation to staphylococcal
      Panton-Valentine leukocidin in vivo.
AB  - The pore-forming toxin Panton-Valentine leukocidin (PVL) is carried by community
      acquired methicillin-resistant Staphylococcus aureus and associated with
      necrotizing pneumonia together with poor prognosis of infected patients. Although
      the cell-death-inducing properties of PVL have previously been examined, the
      pulmonary immune response to PVL is largely unknown. Using an unbiased
      transcriptional profiling approach, we show that PVL induces only 29 genes in
      mouse alveolar macrophages, which are associated with TLR signaling. Further
      studies indicate that PVL directly binds to TLR2 and induces immune responses via
      NF-kappaB in a TLR2, CD14, MyD88, IL-1R-associated kinase 1, and TNFR-associated
      factor 6-dependent manner. PVL-mediated inflammation is independent of pore
      formation but strongly depends on the LukS subunit and is suppressed in
      CD14/TLR2(-/-) cells. In vivo PVL or LukS induced a robust inflammatory response
      in lungs, which was diminished in CD14/TLR2(-/-) mice. These results highlight
      the proinflammatory properties of PVL and identify CD14/TLR2 as an essential
      receptor complex for PVL-induced lung inflammation.

PMID- 21178008
TI  - Restricted microbiota and absence of cognate TCR antigen leads to an unbalanced
      generation of Th17 cells.
AB  - Retinoic acid-related orphan receptor (ROR)gammat(+) TCRalphabeta(+) cells
      expressing IL-17, termed Th17 cells, are most abundant in the intestinal lamina
      propria. Symbiotic microbiota are required for the generation of Th17 cells, but
      the requirement for microbiota-derived Ag is not documented. In this study, we
      show that normal numbers of Th17 cells develop in the intestine of mice that
      express a single TCR in the absence of cognate Ag, whereas the microbiota remains
      essential for their development. However, such mice, or mice monocolonized with
      the Th17-inducing segmented filamentous bacteria, fail to induce normal numbers
      of Foxp3(+) RORgammat(+) T cells, the regulatory counterpart of IL
      17(+)RORgammat(+) T cells. These results demonstrate that a complex microbiota
      and cognate Ag are required to generate a properly regulated set of RORgammat(+)
      T cells and Th17 cells.

PMID- 21178009
TI  - Transplantation tolerance to a single noninherited MHC class I maternal
      alloantigen studied in a TCR-transgenic mouse model.
AB  - The mechanisms underlying tolerance to noninherited maternal Ags (NIMA) are not
      fully understood. In this study, we designed a double-transgenic model in which
      all the offspring's CD8(+) T cells corresponded to a single clone recognizing the
      K(b) MHC class I protein. In contrast, the mother and the father of the offspring
      differed by the expression of a single Ag, K(b), that served as NIMA. We
      investigated the influence of NIMA exposure on the offspring thymic T cell
      selection during ontogeny and on its peripheral T cell response during adulthood.
      We observed that anti-K(b) thymocytes were exposed to NIMA and became activated
      during fetal life but were not deleted. Strikingly, adult mice exposed to NIMA
      accepted permanently K(b+) heart allografts despite the presence of normal levels
      of anti-K(b) TCR transgenic T cells. Transplant tolerance was associated with a
      lack of a proinflammatory alloreactive T cell response and an
      activation/expansion of T cells producing IL-4 and IL-10. In addition, we
      observed that tolerance to NIMA K(b) was abrogated via depletion of CD4(+) but
      not CD8(+) T cells and could be transferred to naive nonexposed mice via adoptive
      transfer of CD4(+)CD25(high) T cell expressing Foxp3 isolated from NIMA mice.

PMID- 21178010
TI  - Mechanistic role of microRNA-146a in endotoxin-induced differential cross
      regulation of TLR signaling.
AB  - Human TLRs are critical sensors for microbial components leading to the
      production of proinflammatory cytokines that are controlled by various
      mechanisms. Monocytes pretreated with LPS exhibit a state of hyporesponsiveness,
      referred to as cross-tolerance, to both homologous and heterologous ligands,
      which play a broader role in innate immunity. To date, LPS-induced cross
      tolerance has not been examined regarding microRNA expression kinetics. In this
      study, THP-1 monocytes treated with various inflammatory ligands showed a
      continuous amplification of microRNA (miR)-146a over 24 h that is inversely
      correlated to TNF-alpha production. In contrast, inhibition of miR-146a showed a
      reciprocal effect. Thus, the characteristic upregulation of miR-146a in LPS
      exposed THP-1 monocytes was studied for cross-tolerance. Strikingly, in LPS
      tolerized THP-1 monocytes, only miR-146a showed a continuous overexpression,
      suggesting its crucial role in cross-tolerance. Similarly, peptidoglycan-primed
      THP-1 cells showed homologous tolerance associated with miR-146a upregulation.
      Subsequently, interchangeable differential cross-regulation was observed among
      non-LPS ligands. TLR2 and TLR5 ligands showed both homologous and heterologous
      tolerance correlated to miR-146a overexpression. More importantly, inflammatory
      responses to TLR4, TLR2, and TLR5 ligands were reduced due to knockdown of miR
      146a targets IL-1R-associated kinase 1 or TNFR-associated factor 6, suggesting
      the regulatory effect of miR-146a on these TLRs signaling. Transfection of miR
      146a into THP-1 cells caused reduction of TNF-alpha production, mimicking LPS
      induced cross-tolerance. Aside from individual ligands, a whole bacterial
      challenge in LPS-primed THP-1 monocytes was accompanied by less TNF-alpha
      production, which is conversely correlated to miR-146a expression. Our studies
      have thus demonstrated that miR-146a plays a crucial role for in vitro monocytic
      cell-based endotoxin-induced cross-tolerance.

PMID- 21178012
TI  - Persistence of gut mucosal innate immune defenses by enteric alpha-defensin
      expression in the simian immunodeficiency virus model of AIDS.
AB  - Gastrointestinal mucosa is an early target of HIV and a site of viral replication
      and severe CD4(+) T cell depletion. However, effects of HIV infection on gut
      mucosal innate immune defense have not been fully investigated. Intestinal Paneth
      cell-derived alpha-defensins constitute an integral part of the gut mucosal
      innate defense against microbial pathogens. Using the SIV-infected rhesus macaque
      model of AIDS, we examined the level of expression of rhesus enteric alpha
      defensins (REDs) in the jejunal mucosa of rhesus macaques during all stages of
      SIV infection using real-time PCR, in situ hybridization, and
      immunohistochemistry. An increased expression of RED mRNAs was found in PC at the
      base of the crypts in jejunum at all stages of SIV infection as compared with
      uninfected controls. This increase correlated with active viral replication in
      gut-associated lymphoid tissue. Loss of RED protein accumulation in PC was seen
      in animals with simian AIDS. This was associated with the loss of secretory
      granules in PC, suggesting an increase in degranulation during advanced SIV
      disease. The alpha-defensin-mediated innate mucosal immunity was maintained in PC
      throughout the course of SIV infection despite the mucosal CD4(+) T cell
      depletion. The loss of RED protein accumulation and secretion was associated with
      an increased incidence of opportunistic enteric infections and disease
      progression. Our findings suggest that local innate immune defense exerted by PC
      derived defensins contributes to the protection of gut mucosa from opportunistic
      infections during the course of SIV infection.

PMID- 21178011
TI  - A novel role for IFN-stimulated gene factor 3II in IFN-gamma signaling and
      induction of antiviral activity in human cells.
AB  - Type I (e.g., IFN-alpha, IFN-beta) and type II IFNs (IFN-gamma) have antiviral,
      antiproliferative, and immunomodulatory properties. Both types of IFN signal
      through the Jak/STAT pathway to elicit antiviral activity, yet IFN-gamma is
      thought to do so only through STAT1 homodimers, whereas type I IFNs activate both
      STAT1- and STAT2-containing complexes such as IFN-stimulated gene factor 3. In
      this study, we show that IFN-stimulated gene factor 3 containing unphosphorylated
      STAT2 (ISGF3(II)) also plays a role in IFN-gamma-mediated antiviral activity in
      humans. Using phosphorylated STAT1 as a marker for IFN signaling, Western blot
      analysis of IFN-alpha2a-treated human A549 cells revealed that phospho-STAT1
      (Y701) levels peaked at 1 h, decreased by 6 h, and remained at low levels for up
      to 48 h. Cells treated with IFN-gamma showed a biphasic phospho-STAT1 response
      with an early peak at 1-2 h and a second peak at 15-24 h. Gene expression
      microarray following IFN-gamma treatment for 24 h indicated an induction of
      antiviral genes that are induced by IFN-stimulated gene factor 3 and associated
      with a type I IFN response. Induction of these genes by autocrine type I and type
      III IFN signaling was ruled out using neutralizing Abs to these IFNs in
      biological assays and by quantitative RT-PCR. Despite the absence of autocrine
      IFNs, IFN-gamma treatment induced formation of ISGF3(II). This novel
      transcription factor complex binds to IFN-stimulated response element promoter
      sequences, as shown by chromatin immunoprecipitation analysis of the protein
      kinase R promoter. STAT2 and IFN regulatory factor 9 knockdown in A549 cells
      reversed IFN-gamma-mediated IFN-stimulated response element induction and
      antiviral activity, implicating ISGF3(II) formation as a significant component of
      the cellular response and biological activity of IFN-gamma.

PMID- 21178013
TI  - Runx1/Cbfbeta2 complexes are required for lymphoid tissue inducer cell
      differentiation at two developmental stages.
AB  - Hematopoietic lymphoid tissue inducer (LTi) cells are essential for the
      development of secondary lymphoid tissues including lymph nodes and Peyer's
      patches. Two transcription factors, the helix-loop-helix inhibitor Id2 and the
      retinoic acid-related orphan receptor gammat (Rorgammat), have been shown to be
      crucial for LTi cell development. However, it remains unclear how the
      specification of multipotent hematopoietic progenitor cells toward the LTi
      lineage is programmed. In this study, we report impaired lymphoid tissue
      organogenesis in mice in which the function of Runx1/Cbfbeta transcription factor
      complexes was attenuated by the loss of either the distal promoter-derived Runx1
      or Cbfbeta2 variant protein. We found that LTi progenitors in fetal liver,
      defined previously as a lineage marker-negative alpha4beta7 integrin
      (alpha4beta7)(+) IL-7R alpha-chain (IL-7Ralpha)(+) population, can be subdivided
      into Rorgammat-expressing IL-7Ralpha(high) cells and nonexpressing IL
      7Ralpha(mid) cells. Whereas Id2 and Rorgammat are required to direct
      alpha4beta7(+)IL-7Ralpha(mid) cells to become alpha4beta7(+)IL-7Ralpha(high)
      cells, Runx1/Cbfbeta2 complexes are necessary for the emergence of
      alpha4beta7(+)IL-7Ralpha(mid) cells. In addition, the loss of Cbfbeta2, but not
      P1-Runx1, resulted in an inefficient upregulation of Rorgammat in residual
      alpha4beta7(+)IL-7Ralpha(+) LTi cells at anlagen. Our results thus revealed that
      Runx1/Cbfbeta2 complexes regulate the differentiation of LTi cells at two stages:
      an early specification of hematopoietic progenitors toward the LTi lineage and a
      subsequent activation of Rorgammat expression at anlagen.

PMID- 21178014
TI  - CCL20 and beta-defensin-2 induce arrest of human Th17 cells on inflamed
      endothelium in vitro under flow conditions.
AB  - CCR6 is a chemokine receptor that is expressed at the cell surface of Th17 cells,
      an IL-17- and IL-22-secreting population of CD4(+) T cells with antipathogenic,
      as well as inflammatory, properties. In the current study, we have determined the
      involvement of CCR6 in human Th17 lymphocyte migration toward inflamed tissue by
      analyzing the capacity of its ligands to induce arrest of these cells onto
      inflamed endothelium in vitro under flow conditions. We show that polarized, in
      situ-differentiated, skin-derived Th17 clones activated via the TCR-CD3 complex
      produce CCL20 in addition to IL-17 and IL-22. The latter cytokines induce, in a
      synergic fashion, the production of human beta-defensin (hBD)-2, but neither hBD
      1 nor hBD-3, by epidermal keratinocytes. Both CCL20 and hBD-2 are capable of
      inducing the arrest of Th17 cells, but not Th1 or Th2 cells, on HUVEC in an CD54
      dependent manner that is CCR6 specific and independent from the expression of
      CXCR4, reported to be an alternative receptor for hBD-2. In addition, Ag-specific
      activation induces a transient loss of CCR6 expression, both at the
      transcriptional and protein level, which occurs with slow kinetics and is not due
      to endogenous CCL20-mediated internalization of CCR6. Together, these results
      indicate that Ag-specific activation will initially contribute to CCR6-mediated
      Th17 cell trafficking toward and sequestration in inflamed tissue, but that it
      eventually results in a transitory state of nonresponsiveness to further
      stimulation of these cells with CCR6 ligands, thus permitting their subsequent
      migration out of the inflamed site.

PMID- 21178015
TI  - Influenza A inhibits Th17-mediated host defense against bacterial pneumonia in
      mice.
AB  - Staphylococcus aureus is a significant cause of hospital and community acquired
      pneumonia and causes secondary infection after influenza A. Recently, patients
      with hyper-IgE syndrome, who often present with S. aureus infections of the lung
      and skin, were found to have mutations in STAT3, required for Th17 immunity,
      suggesting a potential critical role for Th17 cells in S. aureus pneumonia.
      Indeed, IL-17R(-/-) and IL-22(-/-) mice displayed impaired bacterial clearance of
      S. aureus compared with that of wild-type mice. Mice challenged with influenza A
      PR/8/34 H1N1 and subsequently with S. aureus had increased inflammation and
      decreased clearance of both virus and bacteria. Coinfection resulted in greater
      type I and II IFN production in the lung compared with that with virus infection
      alone. Importantly, influenza A coinfection resulted in substantially decreased
      IL-17, IL-22, and IL-23 production after S. aureus infection. The decrease in S.
      aureus-induced IL-17, IL-22, and IL-23 was independent of type II IFN but
      required type I IFN production in influenza A-infected mice. Furthermore,
      overexpression of IL-23 in influenza A, S. aureus-coinfected mice rescued the
      induction of IL-17 and IL-22 and markedly improved bacterial clearance. These
      data indicate a novel mechanism by which influenza A-induced type I IFNs inhibit
      Th17 immunity and increase susceptibility to secondary bacterial pneumonia.

PMID- 21178016
TI  - CD22 is a recycling receptor that can shuttle cargo between the cell surface and
      endosomal compartments of B cells.
AB  - CD22 is a member of the sialic acid-binding Ig-like lectin (Siglec) family that
      is known to be a regulator of B cell signaling. Its B cell-specific expression
      makes it an attractive target for immunotoxin-mediated B cell depletion therapy
      for the treatment of B cell lymphomas and autoimmune diseases. Although CD22 is
      well documented to be an endocytic receptor, it is believed that after
      internalization, it is targeted for degradation. We show in this study that CD22
      is instead constitutively recycled to the cell surface. We also find that glycan
      ligand-based cargo is released from CD22 and accumulates intracellularly as CD22
      recycles between the cell surface and endosomal compartments. In contrast, Abs to
      CD22 do not accumulate but remain bound to CD22 and recycle to the cell surface.
      The results have implications for development of agents that target CD22 as an
      endocytic receptor for delivery of cytotoxic cargo to B cells.

PMID- 21178017
TI  - Race, sex, and age differences in heart failure-related hospitalizations in a
      southern state: implications for prevention.
AB  - BACKGROUND: Because heart failure (HF) is the final common pathway for most heart
      diseases, we examined its 10-year prevalence trend by race, sex, and age in
      Tennessee. METHODS AND RESULTS: HF hospitalization data from the Tennessee
      Hospital Discharge Data System were analyzed by race, sex, and age. Rates were
      directly age-adjusted using the Year 2000 standard population. Adult (age 20+
      years) inpatient hospitalization for primary diagnosis of HF (HFPD) increased
      from 4.2% in 1997 to 4.5% in 2006. Age-adjusted hospitalization for HF (per 10
      000 population) rose by 11.3% (from 29.3 in 1997 to 32.6 in 2006). Parallel
      changes in secondary HF admissions were also noted. Age-adjusted rates were
      higher among blacks than whites and higher among men than women. The ratios of
      black to white by sex admitted with HFPD in 2006 were highest (9:1) among the
      youngest age categories (20 to 34 and 35 to 44 years). Furthermore, for each age
      category of black men below 65 years, there were higher HF admission rates than
      for white men in the immediate older age category. In 2006, the adjusted rate
      ratios for HFPD in black to white men ages 20 to 34 and 35 to 44 years were odds
      ratio, 4.75; 95% confidence interval, 3.29 to 6.86 and odds ratio, 5.10; 95%
      confidence interval, 4.15 to 6.25, respectively. Hypertension was the independent
      predictor of HF admissions in black men ages 20 to 34 years. CONCLUSIONS: The
      higher occurrence of HF among young adults in general, particularly among young
      black men, highlights the need for prevention by identifying modifiable
      biological and social determinants to reduce cardiovascular health disparities in
      this vulnerable group.

PMID- 21178019
TI  - Adrenal imaging: why, when, what, and how? Part 2. What technique?

PMID- 21178020
TI  - Storing unread radiologic images in a PACS.

PMID- 21178018
TI  - High-sensitivity ST2 for prediction of adverse outcomes in chronic heart failure.
AB  - BACKGROUND: Soluble ST2 reflects activity of an interleukin-33-dependent
      cardioprotective signaling axis and is a diagnostic and prognostic marker in
      acute heart failure. The use of ST2 in chronic heart failure has not been well
      defined. Our objective was to determine whether plasma ST2 levels predict adverse
      outcomes in chronic heart failure in the context of current approaches. METHODS
      AND RESULTS: We determined the association between ST2 level and risk of death or
      transplantation in a multicenter, prospective cohort of 1141 chronic heart
      failure outpatients. Adjusted Cox models, receiver operating characteristic
      analyses, and risk reclassification metrics were used to assess the value of ST2
      in predicting risk beyond currently used factors. After a median of 2.8 years,
      267 patients (23%) died or underwent heart transplantation. Patients in the
      highest ST2 tertile (ST2 >36.3 ng/mL) had a markedly increased risk of adverse
      outcomes compared with the lowest tertile (ST2 <=22.3 ng/mL), with an unadjusted
      hazard ratio of 3.2 (95% confidence interval [CI], 2.2 to 4.7; P<0.0001) that
      remained significant after multivariable adjustment (adjusted hazard ratio, 1.9;
      95% CI, 1.3 to 2.9; P=0.002). In receiver operating characteristic analyses, the
      area under the curve for ST2 was 0.75 (95% CI, 0.69 to 0.79), which was similar
      to N-terminal pro-B-type natriuretic peptide (NT-proBNP) (area under the curve,
      0.77; 95% CI, 0.72 to 0.81; P=0.24 versus ST2) but lower than the Seattle Heart
      Failure Model (area under the curve, 0.81 (95% CI, 0.77 to 0.85; P=0.014 versus
      ST2). Addition of ST2 and NT-proBNP to the Seattle Heart Failure Model
      reclassified 14.9% of patients into more appropriate risk categories (P=0.017).
      CONCLUSIONS: ST2 is a potent marker of risk in chronic heart failure and when
      used in combination with NT-proBNP offers moderate improvement in assessing
      prognosis beyond clinical risk scores.

PMID- 21178021
TI  - Comparing mammograms.

PMID- 21178022
TI  - Organizing pneumonia associated with swine-origin influenza A H1N1 2009 viral
      infection.

PMID- 21178023
TI  - Imaging as a biomarker in Behcet disease: prognostic and therapeutic implications
      of serial pulmonary CT angiography.

PMID- 21178024
TI  - V/Q scanning: a useful alternative to pulmonary CT angiography-- let's not forget
      it.

PMID- 21178025
TI  - Contrast-enhanced gray-scale ultrasound for quantitative evaluation of tumor
      response to chemotherapy: preliminary results with a mouse hepatoma model.
AB  - OBJECTIVE: The purpose of this study was to quantify tumor blood perfusion with
      contrast-enhanced gray-scale ultrasound in the evaluation of tumor response to
      chemotherapy. MATERIALS AND METHODS: Mice bearing H22 hepatoma were treated with
      cisplatin or placebo by intraperitoneal injection. Contrast-enhanced gray-scale
      ultrasound was performed on day 8 after bolus injection of a lipid-based
      ultrasound contrast agent. Regions of interest within the tumor were analyzed
      offline to determine area under the curve, maximum intensity, perfusion index,
      mean transit time, time to peak, and quality of fit. Immediately after imaging,
      mice were euthanized, and tumor tissue was removed for fixation in 10% formalin
      solution. Microvascular density was measured after anti-CD34 staining. RESULTS:
      The volume of treated tumors was significantly smaller than that of control
      tumors (p < 0.001). Treatment with cisplatin resulted in a significant decrease
      in perfusion index and maximum intensity compared with control tumors (p < 0.05).
      There were no significant differences between control and treated tumors (p >
      0.05) with respect to area under the curve, mean transit time, and time to peak.
      The microvascular density of treated tumors was significantly lower than that of
      control tumors (p < 0.001). CONCLUSION: Quantitative analysis of tumor blood
      perfusion with contrast-enhanced ultrasound can be used for noninvasive
      assessment of functional changes in tumors after chemotherapy.

PMID- 21178026
TI  - Gadoxetate disodium-enhanced hepatic MRI: dose-dependent contrast dynamics of
      hepatic parenchyma and portal vein.
AB  - OBJECTIVE: The purpose of this study was to investigate the relative enhancement
      characteristics of the hepatic parenchyma and portal vein during gadoxetate
      disodium-enhanced abdominal MRI and to assess whether contrast between the portal
      vein and the hepatic parenchyma can be improved with higher doses of gadoxetate
      disodium. MATERIALS AND METHODS: A total of 102 patients (61 women, 41 men)
      underwent gadoxetate disodium-enhanced abdominal MRI. They received a weight
      independent dose of 10 mL of gadoxetate disodium, corresponding to a dose
      spectrum of 0.02-0.06 mmol/kg body weight. The patients were assigned to one of
      three dose groups: recommended dose (0.02-0.03 mmol/kg), intermediate dose (0.03
      0.045 mmol/kg), or high dose (0.045-0.06 mmol/kg). The signal-to-noise ratios for
      the portal vein, liver, and the portal vein-to-liver contrast-to-noise ratio were
      calculated for three consecutive arterial phases, one portal venous phase, and
      four delayed imaging phases. RESULTS: The delayed phase images of the liver
      showed statistically significant dose dependency and greater enhancement in the
      intermediate- and high-dose groups (p < 0.01). Analogously, the portal vein also
      exhibited greater enhancement in the two higher-dose groups, but the difference
      was not statistically significant (p > 0.05). Regarding portal vein-to-liver
      contrast, all three groups had a dose-independent fast parallel increase from
      baseline toward maximum contrast followed by a steady decline in contrast with no
      statistically significant differences between dose groups (p > 0.05). CONCLUSION:
      Portal vein-to-liver contrast during gadoxetate disodium-enhanced hepatic MRI
      cannot be improved within a dose spectrum of 0.025-0.06 mmol/kg body weight.

PMID- 21178027
TI  - Bending the curve: the recent marked slowdown in growth of noninvasive diagnostic
      imaging.
AB  - OBJECTIVE: The purpose of this article is to determine whether there has been any
      change in the rapid growth pattern that has characterized noninvasive diagnostic
      imaging in recent years. MATERIALS AND METHODS: The annual nationwide Medicare
      Part B databases were used. All Current Procedural Terminology codes for
      discretionary noninvasive diagnostic imaging were identified. The overall
      utilization rates per 1,000 fee-for-service beneficiaries were calculated from
      1998 through 2008, as were rates by modality. Determination was made as to
      whether studies were interpreted by radiologists or nonradiologist physicians.
      RESULTS: The total utilization rate of noninvasive diagnostic imaging grew at a
      compound annual growth rate of 4.1% from 1998 to 2005, but this decreased to 1.4%
      from 2005 to 2008. From 2005 through 2008, the overall growth trends flattened
      dramatically for MRI and nuclear medicine and abated somewhat for CT, ultrasound,
      and echocardiography. In ambulatory settings, flattening of the advanced imaging
      growth curves was seen in both private offices and hospital outpatient
      facilities. From 1998 to 2005, the compound annual growth rate was 3.4% among
      radiologists and 6.6% among nonradiologist physicians. From 2005 to 2008, the
      compound annual growth rate decreased to 0.8% among radiologists and 1.8% among
      nonradiologists. CONCLUSION: There has been a distinct slowing in the growth of
      discretionary noninvasive diagnostic imaging in the Medicare fee-for-service
      population since 2005. The slowdown has been most pronounced in MRI and nuclear
      medicine. This should allay some of the concerns of policymakers and payers. Both
      before and after 2005, growth was approximately twice as rapid among
      nonradiologist physicians as among radiologists.

PMID- 21178028
TI  - Health care systems of developed non-U.S. nations: strengths, weaknesses, and
      recommendations for the United States--observations from internationally
      recognized imaging specialists.
AB  - OBJECTIVE: The purpose of this article is to survey imaging experts from
      developed nations on their impression of their own health care system and
      recommendations for the U.S. health care system as it seeks to enact health care
      reform. MATERIALS AND METHODS: A survey was sent to individual imaging experts
      from developed nations requesting information on their health care systems (type
      of system, strengths, and weaknesses) and their recommendations for the United
      States. RESULTS: Eighteen respondents from 17 developed nations completed the
      survey. All respondents reported universal health care coverage: four with
      government-operated health care, one with mixed government and private insurance
      operated health care, 10 with predominantly government run with private insurance
      supplementation health care, and one with predominantly private insurance with
      government-operated supplementation health care. The most commonly cited strength
      was universal health care coverage for all citizens. The most commonly cited
      weakness was prolonged wait times. Notably absent was concern by the respondent
      physicians about malpractice litigation. The most commonly cited recommendation
      was the implementation of a universal health care coverage program. CONCLUSION:
      In our survey of 18 imaging experts from 17 nations outside the United States,
      most respondents thought that their nations offered adequate universal health
      care coverage for their citizens, with the primary drawback of long wait times.

PMID- 21178029
TI  - Computed radiography image artifacts revisited.
AB  - OBJECTIVE: Computed radiography (CR) has provided a ready cost-effective
      transition from screen film to digital radiography and a convenient entrance to
      PACS. This article revisits artifacts encountered in CR systems. These artifacts
      may obscure abnormalities, mimic a clinical entity, or hamper image quality.
      CONCLUSION: With the new-generation CR systems, software- and hardware-related
      artifacts have decreased, making operator errors more evident. The purpose of
      this study is to establish the current trend of CR artifacts and the new facets
      in identifying and resolving problems quickly that will help prevent future
      occurrences. This article also brings to light the importance of constant review
      required of this extensively studied topic to avoid diagnostic misadventures.

PMID- 21178030
TI  - Creating a comprehensive customer service program to help convey critical and
      acute results of radiology studies.
AB  - OBJECTIVE: Communication of acute or critical results between the radiology
      department and referring clinicians has been a deficiency of many radiology
      departments. The failure to perform or document these communications can lead to
      poor patient care, patient safety issues, medical-legal issues, and complaints
      from referring clinicians. To mitigate these factors, a communication and
      documentation tool was created and incorporated into our departmental customer
      service program. This article will describe the implementation of a comprehensive
      customer service program in a hospital-based radiology department. MATERIALS AND
      METHODS: A comprehensive customer service program was created in the radiology
      department. Customer service representatives were hired to answer the telephone
      calls to the radiology reading rooms and to help convey radiology results. The
      radiologists, referring clinicians, and customer service representatives were
      then linked via a novel workflow management system. This workflow management
      system provided tools to help facilitate the communication needs of each group.
      The number of studies with results conveyed was recorded from the implementation
      of the workflow management system. RESULTS: Between the implementation of the
      workflow management system on August 1, 2005, and June 1, 2009, 116,844 radiology
      results were conveyed to the referring clinicians and documented in the system.
      This accounts for more than 14% of the 828,516 radiology cases performed in this
      time frame. CONCLUSION: We have been successful in creating a comprehensive
      customer service program to convey and document communication of radiology
      results. This program has been widely used by the ordering clinicians as well as
      radiologists since its inception.

PMID- 21178031
TI  - MRI of the axillary arch muscle: prevalence, anatomic relations, and potential
      consequences.
AB  - OBJECTIVE: The purpose of this study was to use MRI of the shoulder to analyze
      the axillary arch muscle and its anatomic relations to lymph nodes and the
      brachial plexus. MATERIALS AND METHODS: In this retrospective study at a single
      clinic, five observers blinded to the patient's condition assessed images from
      1,109 consecutive initial shoulder MRI examinations for the presence and anatomic
      relations of the axillary arch. MRI interpretation reports were reviewed for
      documentation of previous injuries and upper extremity radicular pain or numbness
      for possible correlations between presence of the arch and symptoms of nerve
      entrapment. Results were reported as prevalence percentage or mean +/- SD with
      95% CI. Groups were compared by use of Student's t test or chi-square test as
      indicated (p < 0.05). RESULTS: An arch muscle was found in 71 of 1,109 (6%)
      examinations, and variability was found in arch insertion and visualization. A
      statistically significant 65 of 71 (92%) arches had a course superficial to the
      lymph nodes. The insertion of 50 of 71 (70%) arches was within 5 mm of the
      brachial neurovascular bundle. Excluding documented injuries, significantly more
      patients with an arch had upper extremity neurologic abnormalities than did
      patients without an arch (p = 0.02). CONCLUSION: The axillary arch muscle is
      situated in such a way that it can conceal lymph nodes and impinge on the
      brachial plexus, causing symptoms of upper extremity nerve entrapment.
      Radiologists' familiarity with the arch can improve their recognition of this
      muscular variant so that they can communicate appropriate clinical correlations
      to referring physicians.

PMID- 21178032
TI  - Lateral approach for radiocarpal wrist arthrography.
AB  - OBJECTIVE: We describe a technique of radiocarpal arthrography using the lateral
      approach. This technique may be used as an alternative to conventional dorsal
      techniques. CONCLUSION: Radiocarpal injection using the lateral approach can be
      considered as an alternative to conventional dorsal approaches in the evaluation
      of wrist pain and instability.

PMID- 21178033
TI  - Career development for residents and beyond: filling in the gaps.

PMID- 21178034
TI  - MRI of the knee joint in asymptomatic adolescent soccer players: a controlled
      study.
AB  - OBJECTIVE: The knee is the joint that is most frequently injured in boys 12-15
      years old who practice soccer, and MRI is an accurate method of diagnosing sports
      related injuries. The objective of this cross-sectional case-control study was to
      evaluate the knees of asymptomatic adolescent soccer players using open MRI.
      SUBJECTS AND METHODS: We evaluated 56 knees of 28 asymptomatic male adolescents
      14-15 years old. Participants were divided into two groups and paired by age and
      weight: soccer players (28 knees) and control subjects (28 knees). All the
      examinations were performed using a 0.35-T open-field MRI unit and were evaluated
      by two experienced radiologists blinded to study groups. Bone marrow signal,
      articular cartilage, meniscus, and fat pad abnormalities and the amount of fluid
      were assessed. RESULTS: In the group of soccer players, 18 knees (64.3%) had one
      or more MRI abnormalities, whereas in the control group nine knees (32.1%) had at
      least one MRI abnormality (p = 0.03). The prevalence of bone marrow edema was
      much greater in the group of soccer players (14 knees, 50%), whereas the same
      abnormality was found in only one knee (3.6%) in the control group (p = 0.0001).
      Other abnormalities that were not statistically significant with regard to study
      group were also found in the two groups: infrapatellar fat pad edema, popliteal
      cysts, and ganglion cysts. CONCLUSION: Bone marrow edema is a prevalent abnormal
      finding on MRI scans of knees of asymptomatic adolescent soccer players. MRI
      findings should be interpreted cautiously and in close correlation with clinical
      findings.

PMID- 21178035
TI  - Repeated chemoembolization followed by laser-induced thermotherapy for liver
      metastasis of breast cancer.
AB  - OBJECTIVE: The purpose of this study was to evaluate local tumor control and
      survival after use of a downstaging protocol of repeated transarterial
      chemoembolization (TACE) with two chemotherapeutic combinations followed by laser
      induced thermotherapy in the care of patients with liver metastasis of breast
      cancer. SUBJECTS AND METHODS: This prospective study included 161 patients with
      liver metastasis of breast cancer origin. TACE (mean, 3.5 [SD, 1.3] sessions per
      patient; range, 1-9 sessions) was performed as downstaging treatment to achieve
      the size and number of metastatic lesions that met the requirements for laser
      induced thermotherapy (diameter < 5 cm, number <= 5). The TACE protocol was
      performed with either mitomycin C alone (n = 53) or mitomycin C in combination
      with gemcitabine (n = 108). RESULTS: In response to TACE overall, the mean
      reduction in diameter based on the longest diameter of the target lesions was
      27%. The difference between diameter reduction in the mitomycin C group and that
      in the mitomycin C-gemcitabine group was not statistically significant (p =
      0.65). The mean survival time of all patients was 32.5 months, calculation
      starting from the first TACE treatment. The mean local tumor control period
      calculated as of completion of therapy was 13 months, and the mean time to
      progression was 8 months. In the mitomycin-gemcitabine group, mean time to
      progression was 10.7 months, and in the mitomycin group it was 6.9 months (p =
      0.5). CONCLUSION: TACE can be used for sufficient downstaging of liver metastatic
      lesions of breast cancer to allow laser-induced thermotherapy. A combination of
      mitomycin C and gemcitabine seems to improve the reduction achieved with TACE.

PMID- 21178036
TI  - Incidence of cholangitis and sepsis associated with percutaneous transhepatic
      biliary drain cholangiography and exchange: a comparison between liver transplant
      and native liver patients.
AB  - OBJECTIVE: The purpose of our study was to determine the rate of sepsis and
      cholangitis associated with percutaneous biliary drain cholangiography and
      subsequent drain exchanges and to compare the incidence of these complications
      between patients with liver transplants and those with native livers. MATERIALS
      AND METHODS: A retrospective review of 154 consecutive patients (100 with liver
      transplants and 54 with native livers) who underwent a total of 910 percutaneous
      biliary drain cholangiography examinations and exchanges (January 2005 to July
      2008) was performed. Cholangitis was defined as fever (> 38.5 degrees C) within
      24 hours after the intervention, and sepsis included cholangitis in addition to
      hemodynamic instability. RESULTS: The overall incidence of cholangitis and sepsis
      after percutaneous biliary drain exchanges was 2.1% (n = 19/910 exchanges) and
      0.4% (n = 4/910 exchanges), respectively. There was no statistically significant
      difference in complications between liver transplant patients versus
      nontransplant patients (p = 0.34 for cholangitis and p = 1.00 for sepsis). The
      mean hospital stay due to postprocedural complications was 2.4 days for
      observation and supportive treatment. None of these patients required an
      intensive care stay. Mean percutaneous biliary drain dwell time in liver
      transplant and nontransplant patients was 6.2 and 1.5 months, respectively.
      Transplant patients were significantly younger (54 versus 67 years; p << 0.05),
      male predominant (70% vs 52%, p = 0.035), and had more severe liver disease (12.2
      vs 8.0 Model for End-Stage Liver Disease [MELD] scores; p << 0.05). CONCLUSION:
      Percutaneous biliary drain cholangiography and exchange is associated with a low
      rate of postprocedure cholangitis and sepsis. These complications require brief
      hospitalizations. Liver transplant patients do not have an increased risk of
      complications despite higher MELD scores and longer intubation periods.

PMID- 21178037
TI  - CT-guided sclerotherapy with ethanol concentration monitoring for treatment of
      renal cysts.
AB  - OBJECTIVE: The purpose of our study was to investigate the value of ethanol
      concentration monitoring for efficacy of CT-guided sclerotherapy of simple renal
      cysts. MATERIALS AND METHODS: For the experimental study, ethanol solutions with
      various concentrations (from 10% to 100% at 10% increments) were scanned with CT;
      the correlation between the CT density values and different ethanol
      concentrations in the ethanol solution were analyzed. For the clinical study, a
      total of 66 consecutive patients with simple renal cysts treated with
      sclerotherapy were retrospectively studied. Of the 66 patients, 45 (group A) did
      not have ethanol concentration monitoring, whereas 21 (group B) had ethanol
      concentration monitoring during the procedure. Treatment results between the two
      groups were compared 6 months later with follow-up ultrasound. RESULTS: In the
      experimental study, there was a linear correlation (r =-0.981) between the CT
      density values and the ethanol concentration (p < 0.05). In the clinical study,
      for group A, 25 of 45 patients (55.5%) showed complete regression of the cysts
      and nine of 45 cases (20%) showed partial regression of the cysts. There was a
      24.5% recurrence rate (11/45) in Group A. In group B, 17 of 21 patients (81%)
      exhibited complete regression of the cyst and four of 21 (19%) showed a partial
      regression of the cyst. There was no recurrence in Group B. CONCLUSION: Our in
      vitro experiment showed a linear correlation between ethanol concentration and CT
      density values. CT density values can be used to measure ethanol concentration.
      Ethanol concentration monitoring during the procedure can improve the success
      rate in CT-guided sclerotherapy for simple renal cysts.

PMID- 21178038
TI  - Contrast-enhanced ultrasound for characterizing lymph nodes with focal cortical
      thickening in patients with cutaneous melanoma.
AB  - OBJECTIVE: The aim of this study was to ascertain the utility of contrast
      enhanced ultrasound in assessing the significance of focal cortical thickening in
      the lymph nodes of patients followed up after surgery for cutaneous melanoma.
      MATERIALS AND METHODS: Ultrasound was used to examine 460 consecutive patients to
      identify nodes with focal hypoechoic cortical thickening. Patients whose nodes
      revealed these features underwent contrast-enhanced ultrasound and ultrasound
      guided fine-needle aspiration cytology (FNAC) focusing on the area of cortical
      thickening. Enhancement in the arterial and parenchymal phases was evaluated: A
      generalized homogeneous or intense enhancement was considered benign and the
      presence of a perfusion defect was considered metastatic. RESULTS: After
      exclusion of 24 patients with frank signs of malignancy at gray-scale ultrasound,
      the study included 436 patients. Focal hypoechoic cortical thickening was seen in
      44 of 436 nodes in as many patients. In 29 nodes, the area of focal thickening
      showed contrast enhancement similar to that of the remaining cortex on contrast
      enhanced ultrasound. In 15 nodes, the area of cortical thickening was less well
      vascularized than the adjacent parenchyma in the arterial phase and there were
      areas with perfusion defects that were more evident in the parenchymal phase.
      FNAC focusing on the areas of focal cortical thickening identified 13 metastatic
      nodes and 31 nodes with benign features. Contrast-enhanced ultrasound compared
      with FNAC correctly classified 42 of 44 nodes, showing a sensitivity of 100% and
      a specificity of 99.5%. CONCLUSION: Although our findings need to be confirmed in
      larger series, they indicate that contrast-enhanced ultrasound can be useful in
      clinical practice for characterizing focal cortical thickening in lymph nodes.
      The exclusion or identification of regional lymph node metastases is of
      fundamental importance in oncologic staging because this issue directly
      influences both the prognosis and the choice of therapeutic strategy.

PMID- 21178040
TI  - High cancer yield and positive predictive value: outcomes at a center routinely
      using preoperative breast MRI for staging.
AB  - OBJECTIVE: The purpose of our study is to report the outcomes at a center that
      routinely uses breast MRI for preoperative staging, regardless of lesion
      histology or patient characteristics. MATERIALS AND METHODS: Five hundred ninety
      two patients with recently diagnosed breast cancer who underwent staging with
      preoperative breast MRI between January 1, 2003, and April 30, 2007, were
      reviewed. Five hundred seventy patients comprised the analysis set. Patient age,
      breast density, index tumor histology, receptor status (ER, PR, and HER2), and
      lymph node status were recorded. Biopsy rates, positive predictive values (PPVs)
      of biopsy, and overall cancer yield were calculated and compared using the chi
      square test across patient age, mammographic breast density, index tumor type,
      receptor status, and lymph node status. RESULTS: Biopsy was recommended and
      performed for 152 of 570 (27%) patients found to have one or more suspicious
      lesions on MRI distinct from the index cancer. Sixty-seven of 152 women who
      underwent biopsy had additional cancers diagnosed, for a PPV of 44%. Overall, 12%
      (67/570) of women had otherwise occult cancers diagnosed by MRI, with 8% having
      additional sites or greater extent of ipsilateral disease and 4% having
      unsuspected contralateral cancer detected by MRI alone. No significant
      differences were found in the probability of detecting an occult cancer on the
      basis of patient age, breast density, index tumor characteristics, or lymph node
      status. CONCLUSION: Breast MRI detects otherwise occult cancer with an overall
      added cancer yield of 12% and a high PPV of 44% when applied to a diverse
      population of patients with newly diagnosed breast cancer.

PMID- 21178039
TI  - Outcome of fetuses with cerebral ventriculomegaly and septum pellucidum leaflet
      abnormalities.
AB  - OBJECTIVE: The objective of this study was to assess the outcomes of the prenatal
      diagnosis of septal leaflet abnormalities in fetuses referred for prenatal
      imaging with a finding of ventriculomegaly. MATERIALS AND METHODS: This study is
      a retrospective review of fetuses with a diagnostic code of septal leaflet
      abnormalities from a larger prospective study. Four hundred twenty-five pregnant
      women with 433 fetuses referred for ventriculomegaly were imaged with ultrasound
      and MRI between July 1, 2003, and May 15, 2009. Four to six radiologists
      independently reviewed sonographic and MR images and recorded lateral ventricular
      diameters at the atrium and frontal horns, ventricular configuration, and the
      presence of ventriculomegaly and of other CNS abnormalities. Final prenatal
      ultrasound, MRI, and overall diagnoses were decided by consensus. Fetuses with a
      diagnostic code of septal leaflet abnormalities were identified, and birth
      outcome, autopsy findings, postnatal imaging, and postnatal follow-up
      examinations were obtained. The analysis of covariance, controlling for
      gestational age, was used to compare ventricular dimensions between fetuses with
      septal leaflet abnormalities and fetuses with isolated ventriculomegaly.
      Interrater agreement for the detection of septal leaflet abnormalities was
      assessed with kappa statistics. Interrater agreement and intrarater agreement for
      frontal horn measurements were assessed by variance components analysis. RESULTS:
      Twenty-three fetuses had septal leaflet abnormalities and 229 had isolated
      ventriculomegaly. Atrial and frontal horn diameters, adjusted for gestational
      age, were 77% and 98% larger, respectively, in fetuses with septal leaflet
      abnormalities than in fetuses with isolated ventriculomegaly (p < 0.0001). Before
      the consensus conference, agreement among ultrasound readers was moderate (kappa
      = 0.54) and among MR readers, good (kappa = 0.69). Additional CNS findings were
      seen on MRI in 12 of 23 fetuses (52%). Eleven pregnancies with septal leaflet
      abnormalities underwent termination and 12 progressed to livebirth; of the 12
      livebirths, three neonates died. Neurodevelopmental follow-up was abnormal in all
      surviving children. CONCLUSION: A septal leaflet abnormality in the setting of
      ventriculomegaly is most frequently associated with other CNS abnormalities and
      is associated with postnatal developmental delay.

PMID- 21178041
TI  - Imaging strategies for right lower quadrant pain in pregnancy.

PMID- 21178042
TI  - Response of arteriovenous malformations to gamma knife therapy evaluated with
      pulsed arterial spin-labeling MRI perfusion.
AB  - OBJECTIVE: The goal of this study was to use pulsed arterial spin-labeling (PASL)
      MRI to evaluate the effect of gamma knife treatment on arteriovenous malformation
      (AVM) blood flow by measuring perfusion of the AVM nidus and nearby vascular
      territories. CONCLUSION: PASL can show and quantify the steal phenomena and the
      relative flow rates within the AVM nidus and may be used to follow AVM perfusion
      over time to assess treatment efficacy.

PMID- 21178043
TI  - Dural sinus thrombosis: sources of error in image interpretation.
AB  - OBJECTIVE: The purpose of this article is to bring some of the potential causes
      of false-positive and false-negative interpretations of dural sinus thrombosis
      (DST) on cross-section imaging studies to the attention of radiologists.
      CONCLUSION: The prompt diagnosis of DST can be important in many cases and a
      false-positive diagnosis can cause a delay in establishing the correct diagnosis
      as well as lead to implementation of inappropriate therapy. We hope that this
      article helps to reduce the number of such cases in the daily practice of the
      reader.

PMID- 21178044
TI  - Current imaging assessment and treatment of intracranial aneurysms.
AB  - OBJECTIVE: This article reviews current neuroimaging techniques used for
      screening, diagnosis, and follow-up of patients with intracranial aneurysms as
      well as neuroendovascular therapeutic options available to patients. CONCLUSION:
      The diagnosis and management of intracranial aneurysms have evolved dramatically
      in the past 20 years. MR angiography and CT angiography allow radiologists to
      reliably and noninvasively diagnose most intracranial aneurysms. Nonoperative
      endovascular techniques for treating intracranial aneurysms are now making
      treatment increasingly safer and more effective.

PMID- 21178045
TI  - Causes of misinterpretation of cross-sectional imaging studies for dissection of
      the craniocervical arteries.
AB  - OBJECTIVE: This review presents some of the more common causes of false-positive
      and false-negative interpretations of cross-sectional imaging studies showing, or
      designed to show, dissection of the carotid or vertebral arteries. CONCLUSION:
      Dissection of the craniocervical arteries is a diagnosis that can be very
      difficult on cross-sectional imaging studies such as CT angiography, MRI, and MR
      angiography.

PMID- 21178046
TI  - Responses to the 10 most frequently asked questions about perfusion CT.
AB  - OBJECTIVE: The objective of this article is to address the 10 most frequently
      asked questions radiologists face when planning, performing, processing, and
      interpreting a perfusion CT study in a patient with clinical suspicion of acute
      ischemic stroke. CONCLUSION: It is important for radiologists using PCT for
      stroke imaging to be familiar with the perfusion software used at their
      institution, with the parameters that can be selected during the post-processing
      and how these may influence the PCT results.

PMID- 21178047
TI  - Dynamic MDCT for localization of occult parathyroid adenomas in 26 patients with
      primary hyperparathyroidism.
AB  - OBJECTIVE: The objective of our study was to evaluate the accuracy of dynamic
      contrast-enhanced 4D MDCT in the preoperative identification of parathyroid
      adenomas in patients with primary hyperparathyroidism (PHPT) and a history of
      failed surgery or unsuccessful localization on standard imaging. MATERIALS AND
      METHODS: Thirty-four patients with PHPT underwent 4D CT. Retrospective blinded
      review of the 4D CT examinations was performed by three radiologists for the
      presence and location of a suspected parathyroid adenoma or adenomas. At the time
      of the study, 25 patients underwent surgical exploration after 4D CT. Twenty
      patients had solitary parathyroid adenomas, two patients had two adenomas
      resected, two patients did not have an adenoma, and one patient had mild four
      gland hyperplasia. One patient did not have PHPT on repeat serum biochemistry.
      Surgical and pathology reports, adenoma enhancement, and biochemical and clinical
      follow-up were reviewed. Data were compared with 4D CT interpretations and
      interobserver reliability was calculated. RESULTS: The mean sensitivity and
      specificity of the three readers for the precise CT localization of adenomas was
      82% (range, 79-88%) and 92% (range, 75-100%), respectively. Overall interobserver
      reliability was excellent (kappa = 0.70; range, kappa = 0.60-0.79). All adenomas
      resected at surgery showed a biochemical response and clinical response. The mean
      densities of the confirmed adenomas were 41, 128, 138, and 109 HU at 0, 30, 60,
      and 90 seconds, respectively. Level II lymph nodes identified in 10 patients
      showed significantly less enhancement at 30 (p = 0.0001) and 60 (p = 0.006)
      seconds compared with surgically proven adenomas. CONCLUSION: Occult parathyroid
      adenoma shows characteristic early enhancement. In this subset of patients, 4D CT
      may improve surgical outcomes and decrease morbidity.

PMID- 21178048
TI  - Recurrence in the thyroidectomy bed: sonographic findings.
AB  - OBJECTIVE: The purpose of this article is to characterize sonographic features of
      differentiated thyroid cancer recurrence in the thyroidectomy bed. MATERIALS AND
      METHODS: Patients referred for biopsy of thyroidectomy bed lesions between
      February 2006 and December 2009 were identified. Patient data and gray-scale and
      color Doppler features were recorded. RESULTS: Results of ultrasound-guided
      biopsies of 30 nodules in 27 patients were reviewed. Twenty-five lesions yielded
      diagnostic findings, including 22 recurrences in 19 patients and three benign
      lesions in three patients. Five biopsies were nondiagnostic. Among the 22
      recurrences, 21 (95%) were hypoechoic and one (5%) was mixed hypoechoic and
      hyperechoic on gray-scale imaging. On Doppler imaging, 100% of recurrences had
      detectable vascularity. Eight lesions (36%) had microcalcifications, and five
      (23%) had coarse calcifications; the average long-axis dimension was 1.5 cm. Of
      the five nondiagnostic lesions, four (80%) were hypoechoic, one (20%) was
      isoechoic, one (20%) had microcalcifications, none had coarse calcifications, and
      two (40%) had vascularity; the average long-axis dimension was 0.6 cm. Of the
      negative lesions, three (100%) were hypoechoic, two (66%) had vascularity, and
      two (66%) had coarse calcifications. No microcalcifications were seen, and the
      average long-axis dimension was 2 cm. Serum thyroglobulin (Tg) or anti-Tg
      antibodies were elevated in 12 (63%) of 19 patients with recurrence (eight [42%]
      with elevated Tg levels and four [21%] with elevated anti-Tg antibody levels).
      CONCLUSION: An ultrasound finding of a hypoechoic thyroidectomy bed lesion with
      internal vascularity and size greater than 6 mm is highly sensitive in predicting
      recurrence. Serum Tg levels were less sensitive than ultrasound in detection of
      recurrence in the thyroidectomy bed.

PMID- 21178049
TI  - Diagnostic value of peritumoral minimum apparent diffusion coefficient for
      differentiation of glioblastoma multiforme from solitary metastatic lesions.
AB  - OBJECTIVE: In glioblastoma multiforme, the peritumoral region may be infiltrated
      with malignant cells in addition to vasogenic edema, whereas in a metastatic
      deposit, the peritumoral areas comprise predominantly vasogenic edema. The
      purpose of this study was to determine whether the minimum apparent diffusion
      coefficient (ADC) can be used to differentiate glioblastoma from solitary
      metastasis on the basis of cellularity levels in the enhancing tumor and in the
      peritumoral region. MATERIALS AND METHODS: Seventy-three patients underwent
      conventional MRI and diffusion-weighted imaging (DWI) before undergoing
      treatment. The minimum ADC was measured in the enhancing tumor, peritumoral
      region, and contralateral normal white matter. To determine whether there was a
      statistical difference between metastasis and glioblastoma, we analyzed patient
      age and sex, minimum ADC value, and ADC ratio of the two groups. A receiver
      operating characteristic (ROC) curve analysis was used to determine the cutoff
      value of the minimum ADC that had the best combination of sensitivity and
      specificity for distinguishing between glioblastoma and metastasis. RESULTS: The
      mean minimum ADC values and mean ADC ratios in the peritumoral regions of
      glioblastomas were significantly higher than those in metastases. However, the
      mean minimum ADC values and mean ADC ratios in enhancing tumors showed no
      statistically significant difference between the two groups. According to ROC
      curve analysis, a cutoff value of 1.302 * 10(-3) mm(2)/s for the minimum
      peritumoral ADC value generated the best combination of sensitivity (82.9%) and
      specificity (78.9%) for distinguishing between glioblastoma and metastasis.
      CONCLUSION: Although the characteristics of solitary metastasis and glioblastoma
      multiforme may be similar on conventional MRI, DWI can offer diagnostic
      information to distinguish between the tumors.

PMID- 21178050
TI  - Right ventricle function assessment by MDCT.
AB  - OBJECTIVE: The right ventricle is often overlooked on chest and even cardiac MDCT
      studies. This article will review the normal anatomy of the right ventricle on
      MDCT and the signs of its functional alterations. CONCLUSION: MDCT signs of right
      ventricular dysfunction should be known and checked in relevant cases, such as
      pulmonary embolism in particular, and in any disease that affects both the
      structure and function of the lungs in general.

PMID- 21178052
TI  - Impact of image quality on the performance of computer-aided detection of
      pulmonary embolism.
AB  - OBJECTIVE: The purpose of this article is to assess the relationship between CT
      image quality and the number and type of false-positive (FP) findings found by a
      prototype computer-aided detection (CAD) algorithm for automatic detection of
      pulmonary embolism (PE). MATERIALS AND METHODS: This retrospective study included
      278 subjects (138 men and 140 women; mean age, 57 years; range, 18-88 years) who
      underwent consecutive CT pulmonary angiographies performed during off hours.
      Twenty-four percent (68/278) of studies were reported as positive for PE. CAD
      findings were classified as true-positive or FP by two independent readers and,
      in cases of discordance, by a third radiologist. Each FP result was classified
      according to underlying cause. The degree of vascular enhancement, image noise,
      motion artifacts, overall quality, and presence of underlying lung disease were
      rated on a 4- or 5-point scale. Chi-square tests and t tests were used to test
      significance of differences. RESULTS: The mean number of FP CAD findings was 4.7
      (median, 2) per examination. Most were caused by veins (30% [389/1,298]) or
      airspace consolidations (22% [286/1,298]). There was a significant positive
      association between the number of FP findings and image noise, motion artifacts,
      low vascular enhancement, low overall quality, and the extent of underlying
      disease. On a per-embolism basis, sensitivity decreased from 70.6% (214/303) for
      scans with zero to five FP findings, to 62.3% (33/53) for scans with six to 10 FP
      findings, to 60% (12/20) for scans with more than 10 FP findings. CONCLUSION:
      There is a strong association between CT image quality and the number of FP
      findings indicated by a CAD algorithm for the detection of PE.

PMID- 21178051
TI  - Myocardial delayed enhancement in pulmonary hypertension: pulmonary hemodynamics,
      right ventricular function, and remodeling.
AB  - OBJECTIVE: The purpose of this study was to assess predictors of MRI-identified
      septal delayed enhancement mass at the right ventricular (RV) insertion sites in
      relation to RV remodeling, altered regional mechanics, and pulmonary hemodynamics
      in patients with suspected pulmonary hypertension (PH). SUBJECTS AND METHODS:
      Thirty-eight patients with suspected PH were evaluated with right heart
      catheterization and cardiac MRI. Ten age- and sex-matched healthy volunteers
      acted as controls for MRI comparison. Septal delayed enhancement mass was
      quantified at the RV insertions. Systolic septal eccentricity index, global RV
      function, and remodeling indexes were quantified with cine images. Peak systolic
      circumferential and longitudinal strain at the sites corresponding to delayed
      enhancement were measured with conventional tagging and fast strain-encoded MRI
      acquisition, respectively. RESULTS: PH was diagnosed in 32 patients. Delayed
      enhancement was found in 31 of 32 patients with PH and in one of six patients in
      whom PH was suspected but proved absent (p = 0.001). No delayed enhancement was
      found in controls. Delayed enhancement mass correlated with pulmonary
      hemodynamics, reduced RV function, increased RV remodeling indexes, and reduced
      eccentricity index. Multiple linear regression analysis showed RV mass index was
      an independent predictor of total delayed enhancement mass (p = 0.017). Regional
      analysis showed delayed enhancement mass was associated with reduced longitudinal
      strain at the basal anterior septal insertion (r = 0.6, p < 0.01). Regression
      analysis showed that basal longitudinal strain remained an independent predictor
      of delayed enhancement mass at the basal anterior septal insertion (p = 0.02).
      CONCLUSION: In PH, total delayed enhancement burden at the RV septal insertions
      is predicted by RV remodeling in response to increased afterload. Local fibrosis
      mass at the anterior septal insertion is associated with reduced regional
      longitudinal contractility at the base.

PMID- 21178053
TI  - CT color mapping of the arterial enhancement fraction of VX2 carcinoma implanted
      in rabbit liver: comparison with perfusion CT.
AB  - OBJECTIVE: The purpose of this study was to compare the arterial enhancement
      fraction (AEF) calculated at multiphasic liver CT with the hepatic perfusion
      index (HPI) measured with cine mode perfusion CT. MATERIALS AND METHODS: Cine
      mode perfusion CT was performed after VX2 tumor implantation in the livers of 10
      rabbits. HPI and its color map were obtained with a computer application. With
      raw data from cine mode perfusion CT, images were extracted in the unenhanced,
      arterial, and portal venous phases to simulate multiphasic liver CT. On the basis
      of simulated multiphasic CT images, the AEF color map was obtained with prototype
      software. HPI and AEF were compared for the same regions of interest in the liver
      parenchyma, whole liver tumor, and viable tumor portion. RESULTS: In the liver
      parenchyma, the mean HPI was 23.3% +/- 2.6% (SD) and the AEF 24.4% +/- 2.8%; in
      whole liver tumor, 73.4% +/- 9.5% and 78.4% +/- 10.5%; and in the viable tumor
      portion, 78.0% +/- 7.7% and 78.3% +/- 7.5%. The differences were not
      statistically significant (p > 0.05, Wilcoxon's signed rank test). Measurement
      agreement between the two parameters was moderate (Bland-Altman 95% limits of
      agreement, -14.9% and 19.2%), but there was a strong positive correlation between
      AEF and HPI (within-subject r = 0.91, p < 0.001). Functional maps of HPI and AEF
      correlated with the histologic findings. CONCLUSION: AEF calculated from
      simulated multiphasic liver CT images correlates strongly with HPI obtained at
      cine mode perfusion CT. Further study of the AEF is warranted to explore its
      value in providing hepatic perfusion information without additional radiation
      exposure.

PMID- 21178054
TI  - Usefulness of diffusion-weighted MRI in diagnosis of upper urinary tract cancer.
AB  - OBJECTIVE: The purpose of this study was to prospectively evaluate the diagnostic
      ability of diffusion-weighted MRI (DWI) for detecting upper urinary tract cancer.
      SUBJECTS AND METHODS: Seventy-six patients (36 women, 40 men; median age, 70
      years) suspected of having upper urinary tract cancer underwent T1- and T2
      weighted imaging and DWI (b values, 0 and 800 s/mm(2)) with or without T1
      weighted dynamic contrast-enhanced MRI (DCE-MRI). Two radiologists independently
      interpreted the images. RESULTS: Of the 76 patients suspected of having upper
      urinary tract cancer, 49 were diagnosed with upper urinary tract cancer and the
      remaining 27 were diagnosed as not having upper urinary tract cancer. The
      sensitivity, specificity, and accuracy of DWI interpretation for each reviewer
      was 92%, 96%, and 93% and 94%, 81%, and 89%, respectively. The sensitivity and
      accuracy of DWI were significantly higher than those of T1- and T2-weighted
      imaging (p < 0.01 and p = 0.03 for reviewer 1 and p < 0.01 for both values for
      reviewer 2), although the specificity did not change. The diagnostic abilities of
      DWI and DCE-MRI were not significantly different. The interobserver agreement of
      DWI between the two reviewers was excellent (kappa score = 0.801). The apparent
      diffusion coefficient values of upper urinary tract cancer with grade 3 were
      significantly lower than those of upper urinary tract cancer with grades 2 and 1
      (p < 0.028). CONCLUSION: DWI provides accurate information for the diagnosis of
      upper urinary tract cancer in a noninvasive manner. The additional use of DWI to
      T1- and T2-weighted imaging increases the sensitivity of MRI in identifying upper
      urinary tract cancer with excellent interobserver agreement. Furthermore, DWI
      could be a useful adjunct to preoperative assessment of histologic grade.

PMID- 21178055
TI  - Metastatic pattern of bladder cancer: correlation with the characteristics of the
      primary tumor.
AB  - OBJECTIVE: The purpose of this study was to evaluate the metastatic pattern of
      muscle-invasive bladder cancer and to correlate the findings with the
      characteristics of the primary tumor. MATERIALS AND METHODS: From a clinic
      population of 392 patients with muscle-invasive (pT2-4) bladder cancer seen at
      our institution from January 2004 through December 2009, we studied the cases of
      150 consecutively registered patients with pathologically proven metastatic
      disease. The metastasis-free intervals and metastatic patterns of different T
      categories were compared by Kruskal-Wallis test and Freeman-Halton extension of
      Fisher's exact test. Patients were divided into two histologic categories, those
      with transitional cell carcinoma and those with atypical histologic features. The
      metastasis-free interval and metastatic pattern of these two groups were compared
      by Mann-Whitney test and Fisher's exact test. RESULTS: The study group consisted
      of 150 patients (116 men [77%], 34 women [23%]; median age, 64 years). The
      transitional cell carcinoma group consisted of 94 (63%) patients and the atypical
      histologic features group of 56 (37%) patients. The most common metastatic sites
      were lymph nodes (104 patients, 69%), bone (71 patients, 47%), lung (55 patients,
      37%), liver (39 patients, 26%), and peritoneum (24 patients, 16%). Patients with
      tumors of a more advanced T category had shorter metastasis-free intervals (p =
      0.001, df = 2). There was no significant difference in the metastatic patterns of
      tumors in the different T categories. Patients with atypical histologic features
      had a shorter median metastasis-free interval (3 months; range, 0-29 months) than
      patients with transitional cell carcinoma (12 months; range, 0-192 months) (p =
      0.0001). Patients with atypical histologic features had a significantly higher
      incidence of peritoneal metastasis (p < 0.0002). CONCLUSION: Lymph nodes, bones,
      lung, liver, and peritoneum are the most common sites of metastasis from bladder
      cancer. Tumors in a more advanced T category and those with atypical histologic
      features metastasize earlier. Tumors with atypical histologic features also have
      a higher frequency of peritoneal metastasis.

PMID- 21178056
TI  - Prostate cancer: comparison of tumor visibility on trace diffusion-weighted
      images and the apparent diffusion coefficient map.
AB  - OBJECTIVE: The purpose of our study was to compare the visibility of prostate
      cancer on trace diffusion-weighted (DW) images and the apparent diffusion
      coefficient (ADC) map. MATERIALS AND METHODS: In this retrospective study, 45
      patients with prostate cancer underwent preoperative MRI, including DW imaging
      (DWI) (b values 0, 500, and 1,000 s/mm(2)). A single observer reviewed the images
      in conjunction with tumor maps constructed from prostatectomy. For 132 peripheral
      zone (PZ) tumor foci, the visibility and contrast relative to benign PZ were
      recorded for T2-weighted imaging, trace DWI b500 images, trace DWI b1,000 images,
      and ADC maps. Trace DWI b1,000 images and ADC maps were compared in terms of
      Gleason score, size, normalized T2 signal intensity, ADC, and normalized ADC of
      visible tumors. RESULTS: For each image set, the percentage of visible tumor foci
      and contrast relative to benign PZ were as follows: T2-weighted imaging, 80.3%
      and 0.411; trace DWI b500, 26.5% and 0.131; trace DWI b1,000, 46.2% and 0.119;
      and ADC maps, 62.1% and 0.309. Forty-seven tumor foci were visible on both trace
      DWI b1,000 images and ADC maps, 14 only on trace DWI b1,000 images, 35 only on
      ADC maps, and 36 on neither image set. There was no significant difference in
      Gleason score, size, normalized T2 signal intensity, ADC, or normalized ADC
      between tumors visible only on trace DWI b1,000 images and those visible only on
      ADC maps. CONCLUSION: Given a greater proportion of tumors visible on the ADC map
      than trace DWI and greater contrast relative to benign PZ on the ADC map, we
      suggest that, when performing DWI of the prostate, careful attention be given to
      the ADC map for tumor identification.

PMID- 21178057
TI  - Masters of radiology panel discussion: Models for health care performance in
      radiology--how do we measure our productivity and ourselves?

PMID- 21178058
TI  - Radiology 2011: the big picture.
AB  - OBJECTIVE: This article will take a big-picture view of the issues of
      utilization, cost, value, quality, innovation, self-referral, specialization,
      commoditization, competition, and corporatization and suggest how they are
      closely interrelated. CONCLUSION: These issues may have a major effect on the
      practice of radiology. It may be both presumptuous and platitudinous to suggest
      that our profession currently faces some of the greatest challenges in its
      history.

PMID- 21178059
TI  - Regarding the value reported for the term "spatial gradient magnetic field" and
      how this information is applied to labeling of medical implants and devices.

PMID- 21178060
TI  - Body CT during pregnancy: utilization trends, examination indications, and fetal
      radiation doses.
AB  - OBJECTIVE: The objective of our study was to analyze body CT utilization trends,
      indications, fetal radiation doses, and scanning parameters associated with high
      fetal radiation doses (defined as > 30 mGy). MATERIALS AND METHODS: A
      retrospective review of all chest and abdominopelvic CT examinations performed
      between 1998 and 2005 of patients known to be pregnant was conducted.
      Demographics, gestational age, examination indication, and scan parameters were
      recorded. Fetal radiation dose was calculated for those abdominopelvic
      examinations with direct fetal irradiation. RESULTS: From a database of more than
      170,000 chest and more than 180,000 abdominopelvic CT examinations, 74 chest and
      86 abdominopelvic examinations of pregnant patients were identified. Chest CT use
      increased on average 75%/y/1,000 deliveries in pregnancy versus 19%/y increase in
      all patients (p = 0.2700). Abdominopelvic CT utilization increase was on average
      22%/y/1,000 deliveries in pregnant patients versus 13%/y increase in all patients
      (p = 0.1865). The most common indication for chest CT during pregnancy was
      suspected pulmonary embolism (85%, 63/74) and for abdominopelvic CT, suspected
      appendicitis (58%, 50/86). The average fetal dose from abdominopelvic CT was 24.8
      mGy (range, 6.7-56 mGy); one examination exceeded the 50-mGy threshold for
      increased risk of childhood cancer. Scanning parameters associated with a dose of
      more than 30 mGy were a pitch of less than 1 (p = 0.0080) and more than one
      series acquisition (p = 0.0136). CONCLUSION: Growth of CT during pregnancy
      reflects the trend of increased CT utilization in the general population.
      Avoiding use of CT in pregnant patients with suspected appendicitis would
      significantly decrease fetal radiation exposure. Abdominopelvic CT during
      pregnancy should be carefully planned and monitored so as not to exceed the fetal
      radiation dose for negligible risk.

PMID- 21178061
TI  - Resident education in the radiological sciences: what now?
AB  - OBJECTIVE: With the dizzying changes in the rapidly evolving profession of
      radiology, the structure of resident education in the associated sciences of
      imaging, physics, radiobiology, and radiation effects must be reevaluated
      continually. What roles do these basic radiologic sciences play in bolstering the
      neophyte radiologist on a career of patient care? How should we define the
      spectrum of material that should be learned? How should that spectrum be taught?
      Who decides these things? With the impending changes in the radiology board
      certification process, questions have been raised as to how these changes will
      affect education in a residency program. Should the basic science curriculum be
      enhanced or scaled back? With the emphasis on practical applied physics, what is
      considered old school and what is new school material? CONCLUSION: This article
      describes one approach adopted by a large residency program to address these
      issues.

PMID- 21178062
TI  - Clinical usefulness of adding 3D cartilage imaging sequences to a routine knee MR
      protocol.
AB  - OBJECTIVE: The objective of our study was to determine whether 3D sequences can
      improve the diagnostic performance of a routine MR protocol for detecting
      cartilage lesions within the knee joint at 3 T. SUBJECTS AND METHODS: An
      iterative decomposition of water and fat with echo asymmetry and least-squares
      estimation (IDEAL) spoiled gradient-recalled echo (SPGR) sequence (n = 75
      patients) or an IDEAL gradient-recalled acquisition in a steady state (GRASS)
      sequence (n = 75 patients) was added to routine 3-T knee MR protocol to examine
      150 patients who subsequently underwent arthroscopic knee surgery. Each articular
      surface of the knee joint was graded at arthroscopy. All MR examinations were
      independently reviewed twice by two musculoskeletal radiologists. During the
      first review, the routine MR protocol was used alone to grade each articular
      surface of the knee joint; during the second review, the routine MR protocol was
      used with IDEAL-SPGR or IDEAL-GRASS. Using arthroscopy as the reference standard,
      the sensitivity and specificity for detecting cartilage lesions and the
      proportion of correctly graded cartilage lesions were determined for the routine
      MR protocol alone and for the routine MR protocol with IDEAL-SPGR or IDEAL-GRASS.
      The McNemar test was used to compare sensitivity, specificity, and accuracy
      values and proportions of correctly graded cartilage lesions. RESULTS: There was
      a statistically significant improvement in the specificity (p < 0.05) but not the
      sensitivity (p = 0.08-0.32) for detecting cartilage lesions when using the
      routine MR protocol with IDEAL-SPGR or IDEAL-GRASS. There was also a
      statistically significant (p < 0.05) improvement in the proportion of correctly
      graded cartilage lesions when using the routine MR protocol with IDEAL-SPGR or
      with IDEAL-GRASS. CONCLUSION: Adding 3D sequences to a routine MR protocol
      improves the diagnostic performance for detecting cartilage lesions within the
      knee joint at 3 T.

PMID- 21178063
TI  - The vascular groove sign: a new CT finding associated with osteoid osteomas.
AB  - OBJECTIVE: We have observed that osteoid osteomas are frequently surrounded by
      thin curvilinear or serpiginous low-density grooves in the surrounding bone on CT
      examinations. We believe that these grooves represent prominent enlarged feeding
      arterioles, corresponding to recently published histologic findings. This study
      was performed to assess the sensitivity and specificity of this vascular groove
      sign for differentiating osteoid osteomas from other radiolucent bone lesions.
      MATERIALS AND METHODS: The study group consisted of 42 patients with
      pathologically proven osteoid osteomas. The control group included 29 patients
      with radiolucent bone lesions other than osteoid osteomas. Two readers scored CT
      examinations of these lesions for the presence of the vascular groove sign,
      defined as one or more radiolucent linear or serpiginous grooves extending from
      the periosteal surface of bone down to the radiolucent tumor. Sensitivity and
      specificity values were calculated for each reader. Positive and negative
      predictive values, p values, and interobserver agreement values were calculated.
      RESULTS: The sensitivity of the vascular groove sign for detection of osteoid
      osteoma was 73.8% for reader 1 and 76.2% for reader 2, specificity was 96.6% for
      reader 1 and 89.7% for reader 2, positive predictive value was 96.9% for reader 1
      and 91.4% for reader 2, and negative predictive value was 71.8% for reader 1 and
      72.2% for reader 2. The p value was less than 0.0001 for both readers. The
      interobserver agreement was very good, with a kappa value of 0.85. CONCLUSION:
      The vascular groove sign is a moderately sensitive but highly specific sign for
      distinguishing osteoid osteomas from other radiolucent bone tumors on CT.

PMID- 21178064
TI  - Altered hepatic metabolic activity in patients with hepatic steatosis on FDG
      PET/CT.
AB  - OBJECTIVE: FDG PET studies frequently use the liver as an internal reference
      organ to assess the significance of FDG uptake in pathologic processes involving
      other organs. The purpose of this study was to assess whether hepatic steatosis
      has a significant effect on the standardized uptake value (SUV) of the liver.
      SUBJECTS AND METHODS: This prospective case-control study analyzed FDG PET/CT
      scans of patients with frank hepatic steatosis on the unenhanced CT portion of
      the study. Maximum SUVs (corrected for both body weight [SUV(bw)] and lean body
      mass [SUV(lbm)]) in 37 patients with hepatic steatosis were compared with those
      in 37 control patients without hepatic steatosis. RESULTS: Patients with hepatic
      steatosis had statistically significant smaller mean (+/- SD) values than did the
      control subjects for liver SUV(lbm) (1.91 +/- 0.57 vs 2.17 +/- 0.36), liver
      SUV(lbm)-mediastinum ratio (1.23 +/- 0.19 vs 1.35 +/- 0.19), and liver SUV(bw)
      mediastinum ratio (1.24 +/- 0.16 vs 1.39 +/- 0.22). CONCLUSION: Hepatic steatosis
      results in a small statistically significant decrease in hepatic metabolic
      activity, as measured by FDG PET. However, because the degree of change is small,
      compared with healthy control subjects, this decrease is unlikely to have any
      clinical significance on the use of the liver as an internal reference organ.

PMID- 21178065
TI  - Imaging-guided suprapubic bladder tube insertion: experience in the care of 549
      patients.
AB  - OBJECTIVE: Symptomatic bladder outlet obstruction and neurogenic bladder are
      common conditions that frequently necessitate suprapubic insertion of a bladder
      tube. The purpose of this study was to describe an experience with minimally
      invasive imaging-guided percutaneous suprapubic bladder tube placement and the
      clinical and technical success and complications encountered. MATERIALS AND
      METHODS: A total of 585 primary suprapubic bladder tube insertions and 439
      exchanges of suprapubic bladder tubes were performed on 549 patients (469 men, 80
      women; mean age, 66 years; range, 15-106 years). The details of percutaneous tube
      placement (indication, tube type, size at insertion and change, and method of
      insertion) were retrospectively recorded. RESULTS: The technical success rate for
      primary suprapubic bladder tube insertion was 99.6% (547/549) and for exchanges
      was 92.3% (405/439). The clinical success rate for primary insertion was 98.1%
      (572/583), and symptoms were unresolved in 1.9% (11/583). Minor complications
      occurred in 7.2% (42/583) of cases at tube insertion and in 4.8% (21/439) at
      exchange. There was one major complication (a patient needed surgery because the
      small bowel was traversed by a catheter), and there was no procedure-related
      mortality. CONCLUSION: Radiologic imaging-guided percutaneous suprapubic bladder
      tube placement is a safe and effective procedure.

PMID- 21178066
TI  - CT-guided drainage of abdominal abscesses: hydrodissection to create access
      routes for percutaneous drainage.
AB  - OBJECTIVE: The purpose of this article is to determine the clinical effectiveness
      of CT-guided injection of 0.9% saline solution into the retroperitoneal space to
      create access routes for imaging-guided percutaneous abscess drainage. MATERIALS
      AND METHODS: Between January 2005 and December 2008, a radiology database was
      searched to identify patients who underwent CT-guided percutaneous drainage of
      abdominal abscesses using injection of 0.9% saline solution into the
      retroperitoneal space to displace vital structures and create access routes for
      percutaneous drainage. Patient sex and age and the cause, size, and location of
      the abscess were recorded. The volume of 0.9% saline solution used to displace
      the structures was recorded. Technical success of creating an access route and
      procedural success in completing percutaneous drainage were evaluated.
      Complications were recorded. RESULTS: Twelve patients (three men and nine women;
      mean age, 57 years; range, 26-84 years) with 12 abscesses underwent CT-guided
      percutaneous abscess drainage after injection of 0.9% saline solution into the
      retroperitoneum to displace structures and create an access route for drainage.
      The structures displaced using this technique included the ascending colon (n =
      4), descending colon (n = 3), sigmoid colon (n = 2), duodenum (n = 2), and
      stomach (n = 1). The mean volume of 0.9% saline solution used to displace vital
      structures was 225 mL (range, 60-250 mL). Technical success was achieved in all
      12 cases (100%). Procedural success was achieved in 11 (92%) of 12 cases.
      CONCLUSION: CT-guided injection of 0.9% saline solution into the retroperitoneal
      space is associated with a high technical success rate for displacing vital
      structures and creating a percutaneous access route for imaging-guided drainage
      of abdominal abscesses.

PMID- 21178067
TI  - Hemorrhagic complications after Whipple surgery: imaging and radiologic
      intervention.
AB  - OBJECTIVE: The aim of this pictorial essay is to illustrate the radiologic
      patterns, sites of bleeding, and vascular interventional techniques used in the
      management of postpancreatectomy hemorrhage. CONCLUSION: Hemorrhagic
      complications occur in fewer than 10% of patients after Whipple
      pancreatoduodenectomy but account for as many as 38% of deaths. Bleeding
      typically occurs from the stump of the gastroduodenal artery, but other sites of
      bleeding are increasingly recognized.

PMID- 21178068
TI  - Predictive value for malignancy of suspicious breast masses of BI-RADS categories
      4 and 5 using ultrasound elastography and MR diffusion-weighted imaging.
AB  - OBJECTIVE: The aim of this study is to evaluate the ability of ultrasound
      elastography and MR diffusion-weighted imaging (DWI) to predict malignancy of
      breast masses, with subsequent recommendation for biopsy. MATERIALS AND METHODS:
      For 115 breast masses classified as BI-RADS category 4 or 5, which were assessed
      according to combined findings of mammography, B-mode sonography, and dynamic
      contrast-enhanced MRI, two radiologists retrospectively evaluated the elasticity
      scores using ultrasound elastography and the apparent diffusion coefficient (ADC)
      values using MR DWI. The diagnostic abilities of these two techniques were
      analyzed by using univariate and multivariate logistic regression analysis.
      RESULTS: In the analysis of all 115 breast masses, the elasticity score was
      predictive of malignancy, whereas the ADC value was not independently predictive.
      In an analysis of the 52 masses assessed as BI-RADS category 4, the elasticity
      score was found to be a significant predictor of malignancy, compared with the
      ADC value, which was a nonsignificant predictor. In an analysis of the 63 masses
      assessed as BI-RADS category 5, neither the elasticity score nor the ADC value
      was a significant predictor of malignancy. CONCLUSION: Our results show that
      elasticity imaging provides relatively reliable predictions for malignancy,
      especially in BI-RADS category 4 masses, compared with MR DWI.

PMID- 21178069
TI  - Contribution of diffusion-weighted imaging to dynamic contrast-enhanced MRI in
      the characterization of breast tumors.
AB  - OBJECTIVE: The purpose of our study was to evaluate the diagnostic value of an
      imaging protocol that combines dynamic contrast-enhanced MRI (DCE-MRI) and
      diffusion-weighted imaging (DWI) in patients with suspicious breast lesions and
      to determine if additional information provided by DWI improves the diagnostic
      value of breast MRI. MATERIALS AND METHODS: Eighty-four patients with breast
      tumors (37 benign, 47 malignant) underwent DCE-MRI and DWI before biopsy.
      Morphologic and kinetic analyses were performed on DCE-MRI and findings were
      classified according to the BI-RADS lexicon. Apparent diffusion coefficient (ADC)
      values were calculated from the DWI. The ADCs of the benign and malignant lesions
      were compared. For the combined MRI protocol, morphologic kinetic features and
      ADCs were evaluated together. Diagnostic values of DCE-MRI, DWI, and combined MRI
      were calculated. RESULTS: Median ADCs of the benign and malignant lesions were
      1.26 * 10(-3) mm(2)/s and 0.75 * 10(-3) mm(2)/s, respectively. Cutoff value of
      0.92 * 10(-3) mm(2)/s for ADC provided 91.5% sensitivity and 86.5% specificity.
      DCE-MRI alone showed 97.9% sensitivity and 75.7% specificity. The combination of
      DCE-MRI with DWI provided 95.7% sensitivity and 89.2% specificity. The
      specificity of breast MRI improved by 13.5% (p = 0.063) without a significant
      decrease in the sensitivity (p = 1.000). CONCLUSION: The combination of DWI and
      DCE-MRI has the potential to increase the specificity of breast MRI.

PMID- 21178070
TI  - Background parenchymal enhancement on baseline screening breast MRI: impact on
      biopsy rate and short-interval follow-up.
AB  - OBJECTIVE: Background parenchymal enhancement on breast MRI refers to normal
      enhancement of the patient's fibroglandular tissue. The aim of this study was to
      determine the effect of background parenchymal enhancement on short-interval
      follow-up, biopsy, and cancer detection rate on baseline screening MRI in a high
      risk group. MATERIALS AND METHODS: Two hundred fifty baseline high-risk screening
      MRI examinations were reviewed. For each, the background parenchymal enhancement
      pattern was recorded (minimal, <= 25%; mild, 26-50%; moderate, 51-75%; and
      marked, > 75%), as were BI-RADS category, biopsy rate, and final pathology
      result. Results were compared for each enhancement category. RESULTS: Of the 250
      MRI examinations, 24.8% showed minimal enhancement; 34%, mild; 24%, moderate; and
      17.2%, marked enhancement. Women with minimal enhancement had a significantly
      higher number of BI-RADS categories 1 and 2 examinations (64.5%) than women with
      mild (38.8%), moderate (40%), or marked (25.6%) enhancement. The BI-RADS category
      3 rate was 43.6% overall and was significantly lower for women with minimal
      enhancement (27.4% vs 47.1% for women with mild, 45.0% for women with moderate,
      and 58.1% for women with marked enhancement). At follow-up, 86.2% of the BI-RADS
      3 lesions were converted to BI-RADS category 1 or 2 and 13.8% were converted to
      BI-RADS 4, with a malignancy rate of 0.9% for lesions undergoing short-interval
      follow-up. There was no significant difference in biopsy rate or cancer detection
      rate among enhancement categories. CONCLUSION: Mild, moderate, and marked
      background parenchymal enhancement is associated with a significantly lower rate
      of BI-RADS categories 1 and 2 assessments and a significantly higher rate of BI
      RADS category 3 assessments than minimal enhancement. There was no significant
      difference in biopsy rate or cancer detection rate among the enhancement
      categories.

PMID- 21178071
TI  - Sonographic confirmation of a mammographically detected breast lesion.
AB  - OBJECTIVE: The purpose of this article is to describe a method for efficiently
      and effectively confirming mammographic-sonographic concordance before biopsy.
      CONCLUSION: With the increase in mammographic detection of smaller nonpalpable
      lesions, it is sometimes challenging to confirm that the lesion identified with
      subsequent sonography for additional lesion characterization is the same lesion.
      When additional confirmation is necessary, instillation of radiopaque contrast
      material under sonographic guidance followed by repeat mammography examination
      can help confirm lesion correlation.

PMID- 21178072
TI  - A single-molecule characterization of p53 search on DNA.
AB  - The tumor suppressor p53 slides along DNA while searching for its cognate site.
      Central to this process is the basic C-terminal domain, whose regulatory role and
      its coordination with the core DNA-binding domain is highly debated. Here we use
      single-molecule techniques to characterize the search process and disentangle the
      roles played by these two DNA-binding domains in the search process. We
      demonstrate that the C-terminal domain is capable of rapid translocation, while
      the core domain is unable to slide and instead hops along DNA. These findings are
      integrated into a model, in which the C-terminal domain mediates fast sliding of
      p53, while the core domain samples DNA by frequent dissociation and
      reassociation, allowing for rapid scanning of long DNA regions. The model further
      proposes how modifications of the C-terminal domain can activate "latent" p53 and
      reconciles seemingly contradictory data on the action of different domains and
      their coordination.

PMID- 21178073
TI  - Dioxygenases in Burkholderia ambifaria and Yersinia pestis that hydroxylate the
      outer Kdo unit of lipopolysaccharide.
AB  - Several gram-negative pathogens, including Yersinia pestis, Burkholderia cepacia,
      and Acinetobacter haemolyticus, synthesize an isosteric analog of 3-deoxy-D-manno
      oct-2-ulosonic acid (Kdo), known as D-glycero-D-talo-oct-2-ulosonic acid (Ko), in
      which the axial hydrogen atom at the Kdo 3-position is replaced with OH. Here we
      report a unique Kdo 3-hydroxylase (KdoO) from Burkholderia ambifaria and Yersinia
      pestis, encoded by the bamb_0774 (BakdoO) and the y1812 (YpkdoO) genes,
      respectively. When expressed in heptosyl transferase-deficient Escherichia coli,
      these genes result in conversion of the outer Kdo unit of Kdo(2)-lipid A to Ko in
      an O(2)-dependent manner. KdoO contains the putative iron-binding motif,
      HXDX(n>40)H. Reconstitution of KdoO activity in vitro with Kdo(2)-lipid A as the
      substrate required addition of Fe(2+), alpha-ketoglutarate, and ascorbic acid,
      confirming that KdoO is a Fe(2+)/alpha-ketoglutarate/O(2)-dependent dioxygenase.
      Conversion of Kdo to Ko in Kdo(2)-lipid A conferred reduced susceptibility to
      mild acid hydrolysis. Although two enzymes that catalyze Fe(2+)/alpha
      ketoglutarate/O(2)-dependent hydroxylation of deoxyuridine in fungal extracts
      have been reported previously, kdoO is the first example of a gene encoding a
      deoxy-sugar hydroxylase. Homologues of KdoO are found exclusively in gram
      negative bacteria, including the human pathogens Burkholderia mallei, Yersinia
      pestis, Klebsiella pneumoniae, Legionella longbeachae, and Coxiella burnetii, as
      well as the plant pathogen Ralstonia solanacearum.

PMID- 21178074
TI  - Electron microscopy studies on the quaternary structure of p53 reveal different
      binding modes for p53 tetramers in complex with DNA.
AB  - The multidomain homotetrameric tumor suppressor p53 has two modes of binding
      dsDNA that are thought to be responsible for scanning and recognizing specific
      response elements (REs). The C termini bind nonspecifically to dsDNA. The four
      DNA-binding domains (DBDs) bind REs that have two symmetric 10 base-pair
      sequences. p53 bound to a 20-bp RE has the DBDs enveloping the DNA, which is in
      the center of the molecule surrounded by linker sequences to the tetramerization
      domain (Tet). We investigated by electron microscopy structures of p53 bound to
      DNA sequences consisting of a 20-bp RE with either 12 or 20 bp nonspecific
      extensions on either end. We found a variety of structures that give clues to
      recognition and scanning mechanisms. The 44- and 60-bp sequences gave rise to
      three and four classes of structures, respectively. One was similar to the known
      20-bp structure, but the DBDs in the other classes were loosely arranged and
      incompatible with specific DNA recognition. Some of the complexes had density
      consistent with the C termini extending from Tet to the DNA, adjacent to the
      DBDs. Single-molecule fluorescence resonance energy transfer experiments detected
      the approach of the C termini towards the DBDs on addition of DNA. The structural
      data are consistent with p53 sliding along DNA via its C termini and the DNA
      binding domains hopping on and off during searches for REs. The loose structures
      and posttranslational modifications account for the affinity of nonspecific DNA
      for p53 and point to a mechanism of enhancement of specificity by its binding to
      effector proteins.

PMID- 21178075
TI  - Ramachandran redux.

PMID- 21178077
TI  - Dry cereals fortified with electrolytic iron or ferrous fumarate are equally
      effective in breast-fed infants.
AB  - Precooked, instant (dry) infant cereals in the US are fortified with electrolytic
      iron, a source of low reactivity and suspected low bioavailability. Iron from
      ferrous fumarate is presumed to be more available. In this study, we compared a
      dry infant rice cereal (Cereal L) fortified with electrolytic iron (54.5 mg
      iron/100 g cereal) to a similar cereal (Cereal M) fortified with ferrous fumarate
      (52.2 mg Fe/100 g) for efficacy in maintaining iron status and preventing iron
      deficiency (ID) in breast-fed infants. Ascorbic acid was included in both
      cereals. In this prospective, randomized double-blind trial, exclusively breast
      fed infants were enrolled at 1 mo and iron status was determined periodically. At
      4 mo, 3 infants had ID anemia and were excluded. Ninety-five infants were
      randomized at 4 mo, and 69 (36 Cereal L, 33 Cereal M) completed the intervention
      at 9 mo. From 4 to 9 mo, they consumed daily one of the study cereals. With each
      cereal, 2 infants had mild ID, a prevalence of 4.2%, but no infant developed ID
      anemia. There were no differences in iron status between study groups. Iron
      intake from the study cereals was (mean +/- SD) 1.21 +/- 0.31 mg?kg(-1)?d(-1)
      from Cereal L and 1.07 +/- 0.40 mg?kg(-1)?d(-1) from Cereal M. Eleven infants had
      low birth iron endowment (plasma ferritin < 55 MUg/L at 2 mo) and 54% of these
      infants had ID with or without anemia by 4 mo. We conclude that electrolytic iron
      and ferrous fumarate were equally efficacious as fortificants of this infant
      cereal.

PMID- 21178076
TI  - Docosahexaenoic acid supplementation from mid-pregnancy to parturition influenced
      breast milk fatty acid concentrations at 1 month postpartum in Mexican women.
AB  - (n-3) PUFA, including DHA, are essential for neural development and accumulate
      extensively in the fetal and infant brain. (n-3) PUFA concentrations in breast
      milk, which are largely dependent on maternal diet and tissue stores, are
      correlated with infant PUFA status. We investigated the effect of prenatal DHA
      supplementation on PUFA concentrations in breast milk at 1 mo postpartum. In a
      double-blind, randomized, controlled trial conducted in Mexico, pregnant women
      were supplemented daily with 400 mg DHA or placebo from 18-22 wk gestation to
      parturition. Fatty acid concentrations in breast milk obtained from 174 women at
      1 mo postpartum were determined using GLC and were expressed as % by weight of
      total detected fatty acids. Breast milk DHA concentrations in the DHA and placebo
      groups were (mean +/- SD) 0.20 +/- 0.06 and 0.17 +/- 0.07 (P < 0.01),
      respectively, and those of alpha-linolenic acid (ALA) were 1.38 +/- 0.47 and 1.24
      +/- 0.46 (P = 0.01), respectively. Concentrations of EPA and arachidonic acid did
      not differ between groups (P > 0.05). Maternal plasma DHA concentrations at 1 mo
      postpartum correlated positively with breast milk DHA at 1 mo postpartum in both
      the placebo and DHA groups (r = 0.4; P < 0.01 for both treatment groups).
      Prenatal DHA supplementation from 18-22 wk gestation to parturition increased
      concentrations of DHA and ALA in breast milk at 1 mo postpartum, providing a
      mechanism through which breast-fed infants could benefit.

PMID- 21178078
TI  - Maternal zinc supplementation during pregnancy affects autonomic function of
      Peruvian children assessed at 54 months of age.
AB  - Maternal prenatal zinc supplementation improved fetal autonomic regulation in a
      nutrient-deficient population in Peru. To evaluate whether differences in
      autonomic regulation existed in early childhood, we studied 165 children from a
      zinc supplementation trial (80% of original sample) as part of a comprehensive
      evaluation at age 54 mo. Electrocardiogram (ECG) data were collected from the
      children at rest and while they underwent a cognitive testing battery following a
      standardized protocol. Of these, 79 were born to mothers receiving 25 mg/d zinc
      in addition to 60 mg/d iron and 250 MUg/d folic acid during pregnancy, and 86
      were born to mothers receiving iron and folic acid only. Derived cardiac measures
      included heart period (HP), range, HP variability (HPV), mean square of
      successive differences (MSSD), and a measure of vagal tone (V). Children in the
      zinc supplementation group had greater HP (i.e. slower heart rate), greater
      range, higher time-independent (HPV) and time-dependent (MSSD) variability in HP,
      and higher V (P < 0.05) during baseline. Analyses conducted across the cognitive
      testing period revealed similar effects of prenatal zinc supplementation on
      cardiac patterns. Concurrent child zinc plasma concentration was also associated
      with longer HP, greater variability, and marginally higher range and V (P <
      0.10). Differences in cardiac patterns due to prenatal zinc supplementation were
      detectable in children at 54 mo of age during conditions of both rest and
      challenge, indicating that supplementing zinc-deficient pregnant women has
      beneficial long-term consequences for neural development associated with
      autonomic regulation.

PMID- 21178079
TI  - Serum 25-hydroxyvitamin D is not associated with insulin resistance or beta cell
      function in Canadian Cree.
AB  - Epidemiological studies report inverse associations between blood vitamin D, as
      measured by 25-hydroxyvitamin D [25(OH)D] concentrations, and insulin resistance
      (IR) among predominantly overweight individuals. In a cross-sectional survey of 5
      Cree communities in Quebec, Canada, we determined if 25(OH)D is associated with
      IR and beta-cell function in a largely obese, ethnic minority at high risk of
      developing type 2 diabetes. A total of 510 participants (>=18 y) without type 1
      or type 2 diabetes, assessed for serum 25(OH)D, fasting plasma glucose and
      insulin, and anthropometric and lifestyle variables, were included in the
      analyses. Multivariable linear regressions adjusted for covariates were performed
      for homeostasis model assessment of IR (HOMA-IR) and beta-cell function (HOMA-B)
      in relation to serum 25(OH)D. Serum 25(OH)D (per 10 nmol/L increment) was
      inversely associated with HOMA-IR (beta = -0.005; SE = 0.002; P = 0.004) and HOMA
      B (beta = -0.004; SE = 0.002; P = 0.006) in models adjusted for age, sex,
      physical activity, education, alcohol consumption, and smoking. When further
      adjusted for BMI, associations were no longer significant for either HOMA-IR
      (beta = 0.001, SE = 0.002, P = 0.572) or HOMA-B (beta = 0.001, SE = 0.001, P =
      0.498). The modest inverse associations between 25(OH)D and IR reported
      previously were not observed in this population after adjusting for adiposity.
      Future longitudinal studies investigating the interrelationship among 25(OH)D,
      adiposity, and the risk of developing metabolic syndrome and type 2 diabetes are
      warranted.

PMID- 21178080
TI  - Food prices are associated with dietary quality, fast food consumption, and body
      mass index among U.S. children and adolescents.
AB  - Food prices are expected to affect dietary intakes, however, previous findings
      are mixed and few are based on nationally representative data. We examined the
      associations of price indices of fast foods (FF-PI) and fruits and vegetables (FV
      PI) with dietary intakes and BMI among U.S. children and adolescents using data
      from the Continuing Survey of Food Intakes by Individuals (CSFII; 1994-1998) for
      6759 children (2-9 y) and 1679 adolescents (10-18 y). FF-PI and FV-PI were linked
      to individuals' CSFII dietary data through city-level geocodes. Main outcomes
      included intakes of selected nutrients and food groups, a fast food consumption
      index (FF-CI), diet quality using the 2005 Healthy Eating Index (HEI), and BMI.
      Among children (2-9 y), a higher FF-PI (by $1) was associated with intakes of
      lower FF-CI (beta +/- SE: -0.9 +/- 0.3 count/d), higher HEI (6.6 +/- 2.5), higher
      intakes of fiber (2.7 +/- 0.7 g/d), calcium (225.7 +/- 52.3 mg/d), dairy (172.5
      +/- 36.2 g/d), and fruits and vegetables (113.3 +/- 23.4 cup equivalents/d). FV
      PI was inversely related to fiber intake (beta +/- SE: -3.3 +/- 1.5 g/d) and
      positively associated with BMI (4.3 +/- 1.2 kg/m(2)). Less consistent findings
      were ascribed to FV-PI and among adolescents (10-18 y). Significant associations
      were almost equally balanced between low and high family income groups, with some
      significant interactions between food prices and family income observed,
      particularly among children (2-9 y). Our findings suggest that among U.S.
      children aged 2-9 y, higher FF-PI is associated with better dietary quality,
      whereas higher FV-PI is linked to higher BMI and lower fiber intake. Associations
      varied by family income in children for many dietary intake variables.

PMID- 21178082
TI  - Growth to age 18 months following prenatal supplementation with docosahexaenoic
      acid differs by maternal gravidity in Mexico.
AB  - Little is known about the long-term effects of DHA intake during pregnancy.
      Offspring of primagravid Mexican women who received 400 mg/d DHA from wk 20 of
      gestation through delivery were heavier and had larger head circumferences at
      birth than children whose mothers received placebo; no effect was observed in
      offspring of multigravidae. We have followed these children (n = 739; 76% of the
      birth cohort), measuring length, weight, and head circumference at 1, 3, 6, 9,
      12, and 18 mo. At 18 mo, intent-to-treat differences between placebo and DHA,
      adjusted for maternal height and child sex and age at measurement, were: length, 
      0.21 cm (95% CI = -0.58, 0.15); weight, -0.03 kg (95% CI =-0.19, 0.13); and head
      circumference, 0.02 cm (95% CI = -0.18, 0.21) (all P > 0.05). There was
      heterogeneity of associations by maternal gravidity for weight (P < 0.08), length
      (P < 0.02), and head circumference (P < 0.05). Among offspring of primagravid
      women, length at 18 mo was increased by 0.72 cm (95% CI = 0.11, 1.33) following
      DHA supplementation, representing 0.26 length-for-age Z-score units; among
      offspring of multigravidae, the estimate was -0.13 cm (95% CI = -0.59, 0.32) (P >
      0.5). Maternal DHA supplementation during the second half of gestation may
      enhance growth through 18 mo of children born to primagravid women.

PMID- 21178081
TI  - Marine fatty acid intake is associated with breast cancer prognosis.
AB  - EPA and DHA, long-chain (n-3) PUFA largely obtained from fish, inhibit the
      proliferation of breast cancer cells in vitro and reduce the initiation and
      progression of breast tumors in laboratory animals. Our purpose in this analysis
      was to examine whether intake of these marine fatty acids (EPA and DHA) were
      associated with prognosis in a cohort of women who had been diagnosed and treated
      for early stage breast cancer (n = 3,081). Median follow-up was 7.3 y. Dietary
      intake was assessed using 24-h recalls (~4 recalls per dietary assessment
      obtained at 7 time points over 6 y). Survival models with time-dependent
      covariates were used to examine the association of repeated measures of dietary
      intake of EPA and DHA from food (i.e., marine sources) and supplements with
      disease-free survival and overall survival. Women with higher intakes of EPA and
      DHA from food had an approximate 25% reduced risk of additional breast cancer
      events [tertile 2: HR = 0.74 (95% CI = 0.58-0.94); tertile 3: HR = 0.72 (95% CI =
      0.57-0.90)] compared with the lowest tertile of intake. Women with higher intakes
      of EPA and DHA from food had a dose-dependent reduced risk of all-cause mortality
      [tertile 2: HR = 0.75 (95% CI = 0.55-1.04); tertile 3: HR = 0.59 (95% CI = 0.43
      0.82)]. EPA and DHA intake from fish oil supplements was not associated with
      breast cancer outcomes. The investigation indicates that marine fatty acids from
      food are associated with reduced risk of additional breast cancer events and all
      cause mortality.

PMID- 21178083
TI  - Maternal docosahexaenoic acid supplementation decreases lung inflammation in
      hyperoxia-exposed newborn mice.
AB  - DHA is a long-chain fatty acid that has potent antiinflammatory properties.
      Whereas maternal DHA dietary supplementation has been shown to improve cognitive
      development in infants fed DHA-supplemented milk, the antiinflammatory effects of
      maternal DHA supplementation on the developing fetus and neonate have not been
      extensively explored. Pregnant C3H/HeN dams were fed purified control or DHA
      supplemented diets (~0.25% of total fat) at embryonic d 16 and consumed these
      diets throughout the study. At birth, the nursing mouse pups were placed in room
      air (RA; 21% O(2)) or >95% O(2) (hyperoxia) for up to 7 d. These studies tested
      the hypothesis that maternal DHA supplementation would decrease inflammation and
      improve alveolarization in the lungs of newborn mouse pups exposed to hyperoxia.
      Survival, inflammatory responses, and lung growth were compared among control
      diet/RA, DHA/RA, control/O(2), and DHA/O(2) pups. There were fewer neutrophils
      and macrophages in lung tissues from pups nursed by DHA-supplemented dams than in
      those nursed by dams fed the control diet at 7 d of hyperoxia exposure (P <
      0.015). Although differences due to hyperoxia exposure were observed, maternal
      diet did not affect keratinocyte-derived chemokine, macrophage inflammatory
      protein-2, IL-1beta, or TNFalpha mRNA levels in pup tissues. Hyperoxia also
      induced NF-kappaB activity, but maternal diet did not affect NF-kappaB or
      PPARgamma activities. In mice, DHA supplementation decreases leukocyte
      infiltration in the offspring exposed to hyperoxia, suggesting a potential role
      for DHA supplementation as a therapy to reduce inflammation in preterm infants.

PMID- 21178084
TI  - Algal docosahexaenoic acid affects plasma lipoprotein particle size distribution
      in overweight and obese adults.
AB  - Fish oils containing both EPA and DHA have been shown to have beneficial
      cardiovascular effects, but less is known about the independent effects of DHA.
      This study was designed to examine the effects of DHA on plasma lipid and
      lipoprotein concentrations and other biomarkers of cardiovascular risk in the
      absence of weight loss. In this randomized, controlled, double-blind trial, 36
      overweight or obese adults were treated with 2 g/d of algal DHA or placebo for
      4.5 mo. Markers of cardiovascular risk were assessed before and after treatment.
      In the DHA-supplemented group, the decrease in mean VLDL particle size (P <=
      0.001) and increases in mean LDL (P <= 0.001) and HDL (P <= 0.001) particle sizes
      were significantly greater than changes in the placebo group. DHA supplementation
      also increased the concentrations of large LDL (P <= 0.001) and large HDL
      particles (P = 0.001) and decreased the concentrations of small LDL (P = 0.009)
      and medium HDL particles (P = 0.001). As calculated using NMR-derived data, DHA
      supplementation reduced VLDL TG (P = 0.009) and total TG concentrations (P =
      0.006). Plasma IL-10 increased with DHA supplementation to a greater extent than
      placebo (P = 0.021), but no other significant changes were observed in glucose
      metabolism, insulin sensitivity, blood pressure, or markers of inflammation with
      DHA. In summary, DHA supplementation resulted in potentially beneficial changes
      in some markers of cardiometabolic risk, whereas other markers were unchanged.

PMID- 21178085
TI  - High intake of folate from food sources is associated with reduced risk of
      esophageal cancer in an Australian population.
AB  - Folate plays a key role in DNA synthesis and methylation. Limited evidence
      suggests high intake may reduce risks of esophageal cancer overall; however,
      associations with esophageal cancer subtypes and Barrett's esophagus (BE), a
      precancerous lesion, remain unexplored. We evaluated the relation between intake
      of folate, B vitamins, and methyl-group donors (methionine, choline, betaine)
      from foods and supplements, polymorphisms in key folate-metabolizing genes, and
      risk of BE, esophageal adenocarcinoma (EAC), and esophageal squamous cell
      carcinoma (ESCC) in 2 population-based case-control studies in Australia. BE
      patients without (n = 266) or with (n = 101) dysplasia were compared with
      population controls (n = 577); similarly, EAC (n = 636) or ESCC (n = 245)
      patients were compared with population controls (n = 1507) using multivariable
      adjusted logistic regression. Increasing intake of folate from foods was
      associated with reduced EAC risk (P-trend = 0.01) and mitigated the increased
      risks of ESCC associated with smoking and alcohol consumption. In contrast, high
      intake of folic acid from supplements was associated with a significantly
      elevated risk of BE with dysplasia. High intakes of riboflavin and methionine
      from food were associated with increased EAC risk, whereas increasing betaine
      intake was associated with reduced risks of BE without (P-trend = 0.004) or with
      dysplasia (P-trend = 0.02). Supplemental thiamin, riboflavin, niacin, and vitamin
      B-12 were associated with increased EAC risk. There were no consistent
      associations between genetic polymorphisms studied and BE or EAC risk. High
      intake of folate-containing foods may reduce risk of EAC, but our data raise the
      possibility that folic acid supplementation may increase risks of BE with
      dysplasia and EAC.

PMID- 21178086
TI  - Dietary, but not supplemental, intakes of carotenoids and vitamin C are
      associated with decreased odds of lower urinary tract symptoms in men.
AB  - Lower urinary tract symptoms (LUTS) in men may be related to micronutrients
      involved in prevention of oxidative damage or cell growth and differentiation. We
      tested the hypothesis that carotenoid, vitamin A, and vitamin C intake were
      inversely associated with total LUTS, voiding, and storage symptoms. We conducted
      a cross-sectional multivariate analysis of 1466 men aged 30-79 y in the Boston
      Area Community Health survey (2002-2005), a population-based random sample
      survey. Data were collected by in-person interview and validated FFQ. Moderate-to
      severe LUTS were defined using the American Urological Symptom Index and analyzed
      using multivariate logistic regression. Overall, men consuming greater dietary
      lycopene, beta-carotene, total carotenoid, or vitamin A had ~40-50% decreased
      odds of LUTS compared with the lowest intake quartiles (e.g. beta-carotene and
      storage symptoms, OR = 0.56, 95% CI = 0.39, 0.82; P-trend = 0.02). Interactions
      were observed between dietary iron and vitamin C or beta-cryptoxanthin, whereby
      inverse associations with LUTS, particularly voiding symptoms, occurred only
      among men with moderate-to-high iron intake (P-interaction = 0.001). High-dose
      supplemental and total vitamin C were positively associated with LUTS (e.g.
      supplemental vitamin C >= 250 mg/d, OR = 1.83, 95% CI = 1.21, 2.77; P-trend =
      0.02). An interaction between beta-carotene and smoking status (P-interaction =
      0.004) indicated greater odds of LUTS with higher beta-carotene intake among
      current smokers. Results suggest that modifying consumption of carotenoids and
      vitamin C may influence LUTS in men.

PMID- 21178087
TI  - Polymorphisms in serine hydroxymethyltransferase 1 and methylenetetrahydrofolate
      reductase interact to increase cardiovascular disease risk in humans.
AB  - The enzymes serine hydroxymethyltransferase 1 (gene name SHMT1) and
      methylenetetrahydrofolate reductase (gene name MTHFR) regulate key reactions in
      folate-mediated one-carbon metabolism. Common genetic variants with the potential
      to influence disease risk exist in both genes. A prior report from the Normative
      Aging Study indicated no association of the SHMT1 rs1979277 SNP with
      cardiovascular disease (CVD), but a strong gene-gene interaction was detected
      with MTHFR rs1801133. We investigated the effect of the SHMT1 rs1979277 SNP and
      the SHMT1 rs1979277-MTHFR rs1801133 interaction in 2 epidemiologic cohort
      studies. In the Nurses' Health Study (NHS), the MTHFR rs1801133 variant genotypes
      were associated with an increased CVD risk and there was an interaction between
      SHMT1 and MTHFR such that the association of the MTHFR rs1801133 CT genotype (vs.
      CC; the TT genotype could not be evaluated) was stronger in the presence of the
      SHMT1 rs1979277 TT genotype (OR = 4.34, 95% CI = 1.2, 16.2; P = 0.049). In the
      Health Professionals Follow-Up Study, the MTHFR rs1801133 genotype was not
      associated with CVD risk, nor was there an interaction with SHMT1 rs1979277. The
      association of genetic variation in the SHMT1 gene, alone and in interaction with
      MTHFR, in relation to CVD risk is relatively understudied at the population level
      and results in the NHS confirmed a past report of gene-gene interaction, which is
      consistent with mechanisms suggested by basic science studies.

PMID- 21178088
TI  - Race and region are associated with nutrient intakes among black and white men in
      the United States.
AB  - Stroke mortality rates and prevalence of several chronic diseases are higher in
      Southern populations and blacks in the US. This study examined the relationships
      of race (black, white) and region (Stroke Belt, Stroke Buckle, other) with
      selected nutrient intakes among black and white American men (n = 9229). The
      Block 98 FFQ assessed dietary intakes and multivariable linear regression
      analysis was used to examine whether race and region were associated with intakes
      of fiber, saturated fat, trans fat, sodium, potassium, magnesium, calcium, and
      cholesterol. Race and region were significant predictors of most nutrient
      intakes. Black men consumed 1.00% lower energy from saturated fat compared with
      white men [multivariable-adjusted beta: 1.00% (95% CI = -0.88, -1.13)]. A
      significant interaction between race and region was detected for trans fat (P <
      0.0001), where intake was significantly lower among black men compared with white
      men only in the Stroke Belt [multivariable-adjusted beta: -0.21 (95% CI = -0.11, 
      0.31)]. Among black men, intakes of sodium, potassium, magnesium, and calcium
      were lower, whereas cholesterol was higher, compared with white men (P < 0.05 for
      all). Comparing regions, men in the Stroke Buckle had the lowest intakes of
      fiber, potassium, magnesium, and calcium compared with those in the Stroke Belt
      and other regions; men in both the Stroke Buckle and Stroke Belt had higher
      intakes of cholesterol compared with those in other regions (P < 0.005 for all).
      Given these observed differences in dietary intakes, more research is needed to
      understand if and how they play a role in the health disparities and chronic
      disease risks observed among racial groups and regions in the US.

PMID- 21178089
TI  - Dietary supplement use in the United States, 2003-2006.
AB  - Dietary supplement use has steadily increased over time since the 1970s; however,
      no current data exist for the U.S. population. Therefore, the purpose of this
      analysis was to estimate dietary supplement use using the NHANES 2003-2006, a
      nationally representative, cross-sectional survey. Dietary supplement use was
      analyzed for the U.S. population (>=1 y of age) by the DRI age groupings.
      Supplement use was measured through a questionnaire and was reported by 49% of
      the U.S. population (44% of males, 53% of females). Multivitamin-multimineral use
      was the most frequently reported dietary supplement (33%). The majority of people
      reported taking only 1 dietary supplement and did so on a daily basis. Dietary
      supplement use was lowest in obese adults and highest among non-Hispanic whites,
      older adults, and those with more than a high-school education. Between 28 and
      30% reported using dietary supplements containing vitamins B-6, B-12, C, A, and
      E; 18-19% reported using iron, selenium, and chromium; and 26-27% reported using
      zinc- and magnesium-containing supplements. Botanical supplement use was more
      common in older than in younger age groups and was lowest in those aged 1-13 y
      but was reported by ~20% of adults. About one-half of the U.S. population and 70%
      of adults >= 71 y use dietary supplements; one-third use multivitamin
      multimineral dietary supplements. Given the widespread use of supplements, data
      should be included with nutrient intakes from foods to correctly determine total
      nutrient exposure.

PMID- 21178090
TI  - Energy allowances for solid fats and added sugars in nutritionally adequate U.S.
      diets estimated at 17-33% by a linear programming model.
AB  - The 2010 Dietary Guidelines Advisory Committee has recommended that no more than
      5-15% of total dietary energy should be derived from solid fats and added sugars
      (SoFAS). The guideline was based on USDA food pattern modeling analyses that met
      the Dietary Reference Intake recommendations and Dietary Guidelines and followed
      typical American eating habits. This study recreated food intake patterns for 6
      of the same gender-age groups by using USDA data sources and a mathematical
      optimization technique known as linear programming. The analytic process
      identified food consumption patterns based on 128 food categories that met the
      nutritional goals for 9 vitamins, 9 minerals, 8 macronutrients, and dietary fiber
      and minimized deviation from typical American eating habits. Linear programming
      Model 1 created gender- and age-specific food patterns that corresponded to
      energy needs for each group. Model 2 created food patterns that were iso-caloric
      with diets observed for that group in the 2001-2002 NHANES. The optimized food
      patterns were evaluated with respect to MyPyramid servings goals, energy density
      [kcal/g (1 kcal = 4.18 kJ)], and energy cost (US$/2000 kcal). The optimized food
      patterns had more servings of vegetables and fruit, lower energy density, and
      higher cost compared with the observed diets. All nutrient goals were met. In
      contrast to the much lower USDA estimates, the 2 models placed SoFAS allowances
      at between 17 and 33% of total energy, depending on energy needs.

PMID- 21178091
TI  - Neighborhood socioeconomic status is associated with serum carotenoid
      concentrations in older, community-dwelling women.
AB  - A high dietary intake of fruit and vegetables has been shown to be protective for
      health. Neighborhood socioeconomic differences may influence the consumption of
      carotenoid-rich foods, as indicated by serum carotenoid concentrations. To test
      this hypothesis, we examined the relationship between neighborhood socioeconomic
      status (SES) and serum carotenoid concentrations in a population-based sample of
      community-dwelling women, aged 70-79 y, who participated in the Women's Health
      and Aging Study II in Baltimore, Maryland. Neighborhood socioeconomic Z-scores
      were derived from characteristics of the census block of the participants. Serum
      carotenoid concentrations were measured at baseline and at 18, 36, 72, 98, and
      108 mo follow-up visits. Neighborhood Z-scores were positively associated with
      serum alpha-carotene (P = 0.0006), beta-carotene (P = 0.07), beta-cryptoxanthin
      (P = 0.03), and lutein+zeaxanthin (P = 0.004) after adjusting for age, race, BMI,
      smoking, inflammation, and season. There was no significant association between
      neighborhood Z-score and serum lycopene. Older, community-dwelling women from
      neighborhoods with lower SES have lower serum carotenoid concentrations, which
      reflect a lower consumption of carotenoid-rich fresh fruits and vegetables.

PMID- 21178092
TI  - The incidence of necrotizing enterocolitis is increased following probiotic
      administration to preterm pigs.
AB  - Preterm birth and necrotizing enterocolitis (NEC) is associated with
      inappropriate gut colonization and immunity, which may be improved by probiotic
      bacteria. Using a preterm pig model of NEC, we investigated the effects of
      probiotics on intestinal structure, function, microbiology, and immunology in the
      immediate postnatal period. Just after birth, caesarean-delivered preterm pigs
      were inoculated with Lactobacillus paracasei, Bifidobacteria animalis, and
      Streptococcus thermophilus (total 2.4 * 10(10)/d) either as live (ProLive, n =
      14) or gamma-irradiated dead bacteria (ProDead, n = 12) and compared with
      controls (n = 14). All pigs received parenteral nutrition for 2 d followed by
      enteral formula feeding until tissue collection on d 5. Compared with control
      pigs, intestinal weight was lower and NEC incidence was higher in both groups
      given probiotics (64-67 vs. 14%; P<0.01). Hexose absorption, brush border enzyme
      activities, and gut barrier function were lower in the ProDead group compared
      with the other groups (P < 0.05), whereas live probiotics induced higher
      expression of the proinflammatory cytokines IL-1alpha and IL-6 (P < 0.05).
      Probiotics minimally affected gut colonization, except that live probiotics
      induced a higher density of B. animalis and lower bacterial diversity in the
      distal intestinal mucosa and lower SCFA concentrations in the colon (P < 0.05).
      The detrimental effects of probiotic bacteria in this study may relate to the
      specific strain and dose combination and may have involved the very immature gut
      immune system and low NEC incidence in the control group. It remains to be
      determined whether similar adverse responses to probiotics occur in preterm
      infants.

PMID- 21178094
TI  - A two-step association study identifies CAV2 rs2270188 single nucleotide
      polymorphism interaction with fat intake in type 2 diabetes risk.
AB  - Multiple genetic and environmental factors underlie the etiology of type 2
      diabetes. To evaluate the influence of the relationship between dietary fat
      intake and single nucleotide polymorphisms (SNPs) in genes involved in fat
      assimilation on disease susceptibility, a 2-step approach using an exploratory
      case-control study (n = 192/384) and an independent, confirmatory case-cohort
      study (n = 614/2248) taken from the same prospective study population (European
      Prospective Investigation into Cancer and Nutrition-Potsdam) was used. Sixty
      three SNPs in 32 genes were initially analyzed. Total intake of fat and fatty
      acid intake were calculated from validated baseline FFQ. The SNP * nutrient
      interaction was tested in multivariate adjusted regression models. The initial
      screening step revealed evidence that, for 4 SNPs (CAV2 rs2270188, DBI rs2084202,
      PPARG rs1801282, and SREBF1 rs2297508), disease susceptibility might depend on
      the amount and quality of fat intake. The insulin receptor regulator CAV2
      rs2270188 G > T SNP was found to interact with dietary fat in the confirmatory
      case-cohort study. Using pooled data, homozygous individuals of the rare T-allele
      showed a 100% greater risk of type 2 diabetes if daily fat intake was increased
      from 30 to 40 % energy. An increase in dietary SFA from 10 to 20 % energy
      predicted an ~200% greater risk of type 2 diabetes. We found preliminary evidence
      that CAV2 rs2270188 interacts with dietary fat to affect risk of type 2 diabetes.

PMID- 21178093
TI  - A micronutrient powder with low doses of highly absorbable iron and zinc reduces
      iron and zinc deficiency and improves weight-for-age Z-scores in South African
      children.
AB  - Micronutrient powders (MNP) are often added to complementary foods high in
      inhibitors of iron and zinc absorption. Most MNP therefore include high amounts
      of iron and zinc, but it is no longer recommended in malarial areas to use
      untargeted MNP that contain the Reference Nutrient Intake for iron in a single
      serving. The aim was to test the efficacy of a low-iron and -zinc (each 2.5 mg)
      MNP containing iron as NaFeEDTA, ascorbic acid (AA), and an exogenous phytase
      active at gut pH. In a double-blind controlled trial, South African school
      children with low iron status (n = 200) were randomized to receive either the MNP
      or the unfortified carrier added just before consumption to a high-phytate maize
      porridge 5 d/wk for 23 wk; primary outcomes were iron and zinc status and a
      secondary outcome was somatic growth. Compared with the control, the MNP
      increased serum ferritin (P < 0.05), body iron stores (P < 0.01) and weight-for
      age Z-scores (P < 0.05) and decreased transferrin receptor (P < 0.05). The
      prevalence of iron deficiency fell by 30.6% (P < 0.01) and the prevalence of zinc
      deficiency decreased by 11.8% (P < 0.05). Absorption of iron from the MNP was
      estimated to be 7-8%. Inclusion of an exogenous phytase combined with NaFeEDTA
      and AA may allow a substantial reduction in the iron dose from existing MNP while
      still delivering adequate iron and zinc. In addition, the MNP is likely to
      enhance absorption of the high native iron content of complementary foods based
      on cereals and/or legumes.

PMID- 21178095
TI  - A minimum of six days of diet recording is needed to assess usual vitamin K
      intake among older adults.
AB  - There is a growing interest in the role of vitamin K in health, especially in
      aging populations. Knowledge of inter- and intra-individual variability of
      dietary vitamin K intake could be useful to accurately assess usual intake and
      rank participants in epidemiological studies. Our objectives were to: 1) estimate
      the variance components of vitamin K intake; 2) investigate whether day of the
      week, season, and energy intake are factors related to intra-individual variance;
      and 3) calculate the requisite number of days to achieve desired degrees of
      accuracy for estimating individual vitamin K intake, ranking individuals and
      estimating regression coefficient. Vitamin K intake was assessed in 939 older
      adults (67-84 y) enrolled in the Quebec Longitudinal Study on Nutrition and
      Successful Aging study using 2 sets of 3 nonconsecutive multiple-pass 24-h
      dietary recalls (24HR) collected 6 mo apart. Each set included 2 weekdays and one
      weekend day. Intra- to inter-individual variance ratios for vitamin K intake were
      3.2 (95% CI = 2.6-3.9) overall, 2.6 (95% CI = 2.1-3.5) for men, and 3.7 (95% CI =
      2.9-5.0) for women. Day of the week (weekdays) and season (May to October) were
      positively and significantly associated with vitamin K intake but explained a
      negligible part of intra-individual variation (<1%). Adjusting for energy intake
      explained <7% of variance and did not affect the variance ratio. Six to 13 24HR
      are required to properly rank individuals according to their usual vitamin K
      intake and limit attenuation of the regression coefficient. These results should
      be considered in studies planning to assess vitamin K intakes in older adults.

PMID- 21178096
TI  - Racial and geographic differences in fish consumption: the REGARDS study.
AB  - BACKGROUND: Omega-3 fatty acids from fish have been shown to have favorable
      effects on platelet aggregation, blood pressure, lipid profile, endothelial
      function, and ischemic stroke risk, but there are limited data on racial and
      geographic differences in fish consumption. METHODS: Reasons for Geographic and
      Racial Differences in Stroke (REGARDS) is a national cohort study that recruited
      30,239 participants age >=45 years with oversampling from the southeastern Stroke
      Belt and Buckle and African Americans (AAs). Centralized phone interviewers
      obtained medical histories and in-home examiners measured weight and height.
      Dietary data for this cross-sectional analysis were collected using the self
      administered Block98 Food Frequency Questionnaire (FFQ). Adequate intake of
      nonfried fish was defined as consumption of >=2 servings per week based on
      American Heart Association guidelines. After excluding the top and bottom 1% of
      total energy intake and individuals who did not answer 85% or more of questions
      on the FFQ, the analysis included 21,675 participants. RESULTS: Only 5,022 (23%)
      participants consumed >=2 servings per week of nonfried fish. In multivariable
      analysis, factors associated with inadequate intake of nonfried fish included
      living in the Stroke Belt (vs non-Belt) (odds ratio [OR] 0.83, 95% confidence
      interval [CI] 0.77-0.90) and living in the Stroke Buckle (vs non-Belt) (OR 0.89,
      95% CI 0.81-0.98); factors associated with >=2 servings per week of fried fish
      included being AA (vs white) (OR 3.59, 95% CI 3.19-4.04), living in the Stroke
      Belt (vs non-Belt) (OR 1.32, 95% CI 1.17-1.50), and living in the Stroke Buckle
      (vs non-Belt) (OR 1.17, 95% CI 1.00-1.36). CONCLUSIONS: Differential consumption
      of fish may contribute to the racial and geographic disparities in stroke.

PMID- 21178097
TI  - Report of the task force on designing clinical trials in early (predementia) AD.
AB  - BACKGROUND: A large number of promising candidate disease-modifying treatments
      for Alzheimer disease (AD) continue to advance into phase II and phase III
      testing. However, most completed trials have failed to demonstrate efficacy, and
      there is growing concern that methodologic difficulties may contribute to these
      clinical trial failures. The optimal time to intervene with such treatments is
      probably in the years prior to the onset of dementia, before the neuropathology
      has progressed to the advanced stage corresponding to clinical dementia. METHOD:
      An international task force of individuals from academia, industry, nonprofit
      foundations, and regulatory agencies was convened to discuss optimal trial design
      in early (predementia) AD. RESULTS: General consensus was reached on key
      principles involving the scope of the AD diagnosis, the selection of subjects for
      trials, outcome measures, and analytical methods. CONCLUSION: A consensus has
      been achieved in support of the testing of candidate treatments in the early
      (predementia) AD population.

PMID- 21178098
TI  - Predicting the severity of Duchenne muscular dystrophy: implications for
      treatment.

PMID- 21178100
TI  - TMEM106B regulates progranulin levels and the penetrance of FTLD in GRN mutation
      carriers.
AB  - OBJECTIVES: To determine whether TMEM106B single nucleotide polymorphisms (SNPs)
      are associated with frontotemporal lobar degeneration (FTLD) in patients with and
      without mutations in progranulin (GRN) and to determine whether TMEM106B
      modulates GRN expression. METHODS: We performed a case-control study of 3 SNPs in
      TMEM106B in 482 patients with clinical and 80 patients with pathologic FTLD-TAR
      DNA-binding protein 43 without GRN mutations, 78 patients with FTLD with GRN
      mutations, and 822 controls. Association analysis of TMEM106B with GRN plasma
      levels was performed in 1,013 controls and TMEM106B and GRN mRNA expression
      levels were correlated in peripheral blood samples from 33 patients with FTLD and
      150 controls. RESULTS: In our complete FTLD patient cohort, nominal significance
      was identified for 2 TMEM106B SNPs (top SNP rs1990622, p(allelic) = 0.036).
      However, the most significant association with risk of FTLD was observed in the
      subgroup of GRN mutation carriers compared to controls (corrected p(allelic) =
      0.0009), where there was a highly significant decrease in the frequency of
      homozygote carriers of the minor alleles of all TMEM106B SNPs (top SNP rs1990622,
      CC genotype frequency 2.6% vs 19.1%, corrected p(recessive) = 0.009). We further
      identified a significant association of TMEM106B SNPs with plasma GRN levels in
      controls (top SNP rs1990622, corrected p = 0.002) and in peripheral blood samples
      a highly significant correlation was observed between TMEM106B and GRN mRNA
      expression in patients with FTLD (r = -0.63, p = 7.7 * 10(-5)) and controls (r = 
      0.49, p = 2.2 * 10(-10)). CONCLUSIONS: In our study, TMEM106B SNPs significantly
      reduced the disease penetrance in patients with GRN mutations, potentially by
      modulating GRN levels. These findings hold promise for the development of future
      protective therapies for FTLD.

PMID- 21178099
TI  - SPP1 genotype is a determinant of disease severity in Duchenne muscular
      dystrophy.
AB  - OBJECTIVE: Duchenne muscular dystrophy (DMD) is the most common single-gene
      lethal disorder. Substantial patient-patient variability in disease onset and
      progression and response to glucocorticoids is seen, suggesting genetic or
      environmental modifiers. METHODS: Two DMD cohorts were used as test and
      validation groups to define genetic modifiers: a Padova longitudinal cohort (n =
      106) and the Cooperative International Neuromuscular Research Group (CINRG) cross
      sectional natural history cohort (n = 156). Single nucleotide polymorphisms to be
      genotyped were selected from mRNA profiling in patients with severe vs mild DMD,
      and genome-wide association studies in metabolism and polymorphisms influencing
      muscle phenotypes in normal volunteers were studied. RESULTS: Effects on both
      disease progression and response to glucocorticoids were observed with
      polymorphism rs28357094 in the gene promoter of SPP1 (osteopontin). The G allele
      (dominant model; 35% of subjects) was associated with more rapid progression
      (Padova cohort log rank p = 0.003), and 12%-19% less grip strength (CINRG cohort
      p = 0.0003). CONCLUSIONS: Osteopontin genotype is a genetic modifier of disease
      severity in Duchenne dystrophy. Inclusion of genotype data as a covariate or in
      inclusion criteria in DMD clinical trials would reduce intersubject variance, and
      increase sensitivity of the trials, particularly in older subjects.

PMID- 21178101
TI  - Arsenic exposure, dietary patterns, and skin lesion risk in bangladesh: a
      prospective study.
AB  - Dietary factors are believed to modulate arsenic toxicity, potentially
      influencing risk of arsenical skin lesions. The authors evaluated associations
      among dietary patterns, arsenic exposure, and skin lesion risk using baseline
      food frequency questionnaire data collected in the Health Effects of Arsenic
      Longitudinal Study (HEALS) in Araihazar, Bangladesh (2000-2009). They identified
      dietary patterns and estimated dietary pattern scores using factor analysis.
      Scores were tested for association with incident skin lesion risk and interaction
      with water arsenic exposure by using ~6 years of follow-up data (814 events among
      9,677 individuals) and discrete time hazards models (adjusting for key
      covariates). The authors identified 3 clear dietary patterns: the "gourd and
      root," "vegetable," and "animal protein" patterns. The gourd and root pattern
      score was inversely associated with skin lesion risk (P(trend) = 0.001), with
      hazard ratios of 0.86, 0.73, and 0.69 for the second, third, and fourth highest
      quartiles. Furthermore, the association between water arsenic and skin lesion
      incidence was stronger among participants with low gourd and root scores
      (multiplicative P(interaction) < 0.001; additive P(interaction) = 0.05). The
      vegetable pattern and animal protein pattern showed similar but weaker
      associations and interactions. Eating a diet rich in gourds and root vegetables
      and increasing dietary diversity may reduce arsenical skin lesion risk in
      Bangladesh.

PMID- 21178103
TI  - Estimates of nondisclosure of cigarette smoking among pregnant and nonpregnant
      women of reproductive age in the United States.
AB  - Although clinic-based studies have used biochemical validation to estimate the
      percentage of pregnant women who deny smoking but are actually smokers, a
      population-based estimate of nondisclosure of smoking status in US pregnant women
      has not been calculated. The authors analyzed data from the 1999-2006 National
      Health and Nutrition Examination Survey and estimated the percentage of 994
      pregnant and 3,203 nonpregnant women 20-44 years of age who did not report
      smoking but had serum cotinine levels that exceeded the defined cut point for
      active smoking (nondisclosure). Active smoking was defined as self-reporting
      smoking or having a serum cotinine concentration that exceeded the cut point for
      active smoking. Overall, 13.0% (95% confidence interval (CI): 8.8, 17.1) of
      pregnant women and 29.7% (95% CI: 27.3, 32.1) of nonpregnant women were active
      smokers. Nondisclosure was higher among pregnant active smokers (22.9%, 95% CI:
      11.8, 34.6) than among nonpregnant smokers (9.2%, 95% CI: 7.1, 11.2). Among
      pregnant active smokers, nondisclosure was associated with younger age (20-24
      years). Among nonpregnant active smokers, nondisclosure was associated with
      Mexican-American and non-Hispanic black race/ethnicity. Studies and surveillance
      systems that rely on self-reported smoking status are subject to underestimation
      of smoking prevalence, especially among pregnant women, and underreporting may
      vary by demographic characteristics.

PMID- 21178102
TI  - Polymorphisms in inflammatory response genes and their association with gastric
      cancer: A HuGE systematic review and meta-analyses.
AB  - To evaluate the association between gastric cancer susceptibility and
      inflammation-related gene polymorphisms, the authors conducted a series of meta
      analyses using a predefined protocol. Genes investigated were those coding for
      the interleukin (IL) proteins (IL1B, IL1RN, IL8, and IL10) and for tumor necrosis
      factor-alpha. Gastric cancers were stratified by histologic subtype and anatomic
      subsite, by Helicobacter pylori infection status, by geographic location (Asian
      or non-Asian study population), and by a quantitative index of study quality. All
      published literature and meeting abstracts from the period 1990-2006 were
      considered. Results consistently supported increased cancer risk for IL1RN2
      carriers; the increased risk was specific to non-Asian populations and was seen
      for intestinal and diffuse cancers, distal cancers, and, to a lesser extent,
      cardia cancers. Analyses restricted to high-quality studies or H. pylori-positive
      cases and controls also showed significant associations with both carrier status
      and homozygosity status. In Asian populations, reduced risk was observed in
      association with IL1B-31C carrier status. This effect was also observed in
      analyses restricted to high-quality studies. These results indicate the
      importance of stratification by anatomic site, histologic type, H. pylori
      infection, and country of origin. Study quality considerations, both laboratory
      and epidemiologic, can also affect results and may explain, in part, the
      variability in results published to date.

PMID- 21178104
TI  - Muscle-specific overexpression of NCOATGK, splice variant of O-GlcNAcase, induces
      skeletal muscle atrophy.
AB  - The protein O-linked beta-N-acetylglucosamine (O-GlcNAc) modification plays an
      important role in skeletal muscle development and physiological function. In this
      study, bitransgenic mice were generated that overexpressed NCOAT(GK), an O
      GlcNAcase-inactive spliced variant of the O-GlcNAcase gene, specifically in
      skeletal muscle using the muscle creatine kinase promoter. Expression of the
      chimeric enhanced green fluorescent protein-NCOAT(GK) transgene caused an
      increase of cellular O-GlcNAc levels, along with the accumulation and activation
      of proapoptotic factors in muscles of bitransgenic mice. The consequence of
      overexpressing the transgene for a 2-wk period was muscle atrophy and, in some
      cases, resulted in the death of male mice. Muscle atrophy is a common
      complication of many diseases, some of which correlate markedly with high
      cellular O-GlcNAc levels, such as diabetes. Our study provides direct evidence
      linking muscle atrophy and the disruption of O-GlcNAcase activity.

PMID- 21178105
TI  - beta4-subunit increases Slo responsiveness to physiological Ca2+ concentrations
      and together with beta1 reduces surface expression of Slo in hair cells.
AB  - Changing kinetics of large-conductance potassium (BK) channels in hair cells of
      nonmammalian vertebrates, including the chick, plays a critical role in
      electrical tuning, a mechanism used by these cells to discriminate between
      different frequencies of sound. BK currents are less abundant in low-frequency
      hair cells and show large openings in response to a rise in intracellular Ca(2+)
      at a hair cell's operating voltage range (spanning -40 to -60 mV). Although the
      molecular underpinnings of its function in hair cells are poorly understood, it
      is established that BK channels consist of a pore-forming alpha-subunit (Slo) and
      a number of accessory subunits. Currents from the alpha (Slo)-subunit alone do
      not show dramatic increases in response to changes in Ca(2+) concentrations at 
      50 mV. We have cloned the chick beta(4)- and beta(1)-subunits and show that these
      subunits are preferentially expressed in low-frequency hair cells, where they
      decrease Slo surface expression. The beta(4)-subunit in particular is responsible
      for the BK channel's increased responsiveness to Ca(2+) at a hair cell's
      operating voltage. In contrast, however, the increases in relaxation times
      induced by both beta-subunits suggest additional mechanisms responsible for BK
      channel function in hair cells.

PMID- 21178106
TI  - Leukemia inhibitory factor regulates trafficking of T-type Ca2+ channels.
AB  - Neuropoietic cytokines such as ciliary neurotrophic factor (CNTF) and leukemia
      inhibitory factor (LIF) stimulate the functional expression of T-type Ca(2+)
      channels in developing sensory neurons. However, the molecular and cellular
      mechanisms involved in the cytokine-evoked membrane expression of T-type Ca(2+)
      channels are not fully understood. In this study we investigated the role of LIF
      in promoting the trafficking of T-type Ca(2+) channels in a heterologous
      expression system. Our results demonstrate that transfection of HEK-293 cells
      with the rat green fluorescent protein (GFP)-tagged T-type Ca(2+) channel
      alpha(1H)-subunit resulted in the generation of transient Ca(2+) currents.
      Overnight treatment of alpha(1H)-GFP-transfected cells with LIF caused a
      significant increase in the functional expression of T-type Ca(2+) channels as
      indicated by changes in current density. LIF also evoked a significant increase
      in membrane fluorescence compared with untreated cells. Disruption of the Golgi
      apparatus with brefeldin A inhibited the stimulatory effect of LIF, indicating
      that protein trafficking regulates the functional expression of T-type Ca(2+)
      channels. Trafficking of alpha(1H)-GFP was also disrupted by cotransfection of
      HEK-293 cells with the dominant-negative form of ADP-ribosylation factor (ARF)1
      but not ARF6, suggesting that ARF1 regulates the LIF-evoked membrane trafficking
      of alpha(1H)-GFP subunits. Trafficking of T-type Ca(2+) channels required
      transient activation of the JAK and ERK signaling pathways since stimulation of
      HEK-293 cells with LIF evoked a considerable increase in the phosphorylation of
      the downstream JAK targets STAT3 and ERK. Pretreatment of HEK-293 cells with the
      JAK inhibitor P6 or the ERK inhibitor U0126 blocked ERK phosphorylation. Both P6
      and U0126 also inhibited the stimulatory effect of LIF on T-type Ca(2+) channel
      expression. These findings demonstrate that cytokines like LIF promote the
      trafficking of T-type Ca(2+) channels.

PMID- 21178107
TI  - Distinct cellular pathways for resistance to urea stress and hypertonic stress.
AB  - During antidiuresis with elevated vasopressin, urea accumulates in the renal
      medulla to very high concentrations, imposing considerable cellular stress. How
      local cells cope with urea stress is relevant to the whole kidney because the
      renal medulla is the major site of residence for the renal stem cells. Previous
      studies showed that renal cells were incapable of preconditioning in moderate
      urea concentrations to enhance resistance to urea stress. Instead,
      preconditioning in moderately high salinity (moderate hypertonicity) has been
      shown to promote resistance to urea stress due to the induction of the molecular
      chaperone heat shock protein 70 (Hsp70), which is mediated by the transcription
      factor tonicity-responsive enhancer binding protein (TonEBP). Here we report that
      cell lines derived from the kidney and fibroblasts display enhanced resistance to
      urea stress after pretreatment in moderate, nonstressful concentrations of urea.
      Using TonEBP knockdown and immunoblot analyses, we demonstrate that TonEBP and
      Hsp70 are dispensable for the increased resistance to urea stress. These data
      suggest that cells in the renal medulla are capable of overcoming urea stress by
      activating distinct cellular pathways.

PMID- 21178109
TI  - Spatial association of the Cav1.2 calcium channel with alpha5beta1-integrin.
AB  - Engagement of alpha(5)beta(1)-integrin by fibronectin (FN) acutely enhances
      Cav1.2 channel (Ca(L)) current in rat arteriolar smooth muscle and human
      embryonic kidney cells (HEK293-T) expressing Ca(L). Using coimmunoprecipitation
      strategies, we show that coassociation of Ca(L) with alpha(5)- or beta(1)
      integrin in HEK293-T cells is specific and depends on cell adhesion to FN. In rat
      arteriolar smooth muscle, coassociations between Ca(L) and alpha(5)beta(1)
      integrin and between Ca(L) and phosphorylated c-Src are also revealed and
      enhanced by FN treatment. Using site-directed mutagenesis of Ca(L) heterologously
      expressed in HEK293-T cells, we identified two regions of Ca(L) required for
      these interactions: 1) COOH-terminal residues Ser(1901) and Tyr(2122), known to
      be phosphorylated by protein kinase A (PKA) and c-Src, respectively; and 2) two
      proline-rich domains (PRDs) near the middle of the COOH terminus.
      Immunofluorescence confocal imaging revealed a moderate degree of wild-type Ca(L)
      colocalization with beta(1)-integrin on the plasma membrane. Collectively, our
      results strongly suggest that 1) upon ligation by FN, Ca(L) associates with
      alpha(5)beta(1)-integrin in a macromolecular complex including PKA, c-Src, and
      potentially other protein kinases; 2) phosphorylation of Ca(L) at Y(2122) and/or
      S(1901) is required for association of Ca(L) with alpha(5)beta(1)-integrin; and
      3) c-Src, via binding to PRDs that reside in the II-III linker region and/or the
      COOH terminus of Ca(L), mediates current potentiation following alpha(5)beta(1)
      integrin engagement. These findings provide new evidence for how interactions
      between alpha(5)beta(1)-integrin and FN can modulate Ca(L) entry and consequently
      alter the physiological function of multiple types of excitable cells.

PMID- 21178110
TI  - Proinflammatory treatment of astrocytes with lipopolysaccharide results in
      augmented Ca2+ signaling through increased expression of via phospholipase A2
      (iPLA2).
AB  - Many Ca(2+)-regulated intracellular processes are involved in the development of
      neuroinflammation. However, the changes of Ca(2+) signaling in the brain under
      inflammatory conditions were hardly studied. ATP-induced Ca(2+) signaling is a
      central event of signal transmission in astrocytic networks. We investigated
      primary astrocytes after proinflammatory stimulation with lipopolysaccharide
      (LPS; 100 ng/ml) for 6-24 h. We reveal that Ca(2+) responses to purinergic ATP
      stimulation are significantly increased in amplitude and duration after
      stimulation with LPS. We detected that increased amplitudes of Ca(2+) responses
      to ATP in LPS-treated astrocytes can be explained by substantial increase of
      Ca(2+) load in stores in endoplasmic reticulum. The mechanism implies enhanced
      Ca(2+) store refilling due to the amplification of capacitative Ca(2+) entry. The
      reason for the increased duration of Ca(2+) responses in LPS-treated cells is
      also the amplified capacitative Ca(2+) entry. Next, we established that the
      molecular mechanism for the LPS-induced amplification of Ca(2+) responses in
      astrocytes is increased expression and activity of VIA phospholipase A(2) (VIA
      iPLA(2)). Indeed, both gene silencing with specific small interfering RNA and
      pharmacological inhibition of VIA iPLA(2) with S-bromoenol lactone reduced the
      load of the Ca(2+) stores and caused a decrease in the amplitudes of Ca(2+)
      responses in LPS-treated astrocytes to values, which were comparable with those
      in untreated cells. Our findings highlight a novel regulatory role of VIA iPLA(2)
      in development of inflammation in brain. We suggest that this enzyme might be a
      possible target for treatment of pathologies related to brain inflammation.

PMID- 21178111
TI  - Metabolic amplification of insulin secretion by glucose is independent of beta
      cell microtubules.
AB  - Glucose-induced insulin secretion (IS) by beta-cells is controlled by two
      pathways. The triggering pathway involves ATP-sensitive potassium (K(ATP))
      channel-dependent depolarization, Ca(2+) influx, and rise in the cytosolic Ca(2+)
      concentration ([Ca(2+)](c)), which triggers exocytosis of insulin granules. The
      metabolic amplifying pathway augments IS without further increasing [Ca(2+)](c).
      After exclusion of the contribution of actin microfilaments, we here tested
      whether amplification implicates microtubule-dependent granule mobilization.
      Mouse islets were treated with nocodazole or taxol, which completely
      depolymerized and polymerized tubulin. They were then perifused to measure
      [Ca(2+)](c) and IS. Metabolic amplification was studied during imposed steady
      elevation of [Ca(2+)](c) by tolbutamide or KCl or by comparing [Ca(2+)](c) and IS
      responses to glucose and tolbutamide. Nocodazole did not alter [Ca(2+)](c) or IS
      changes induced by the three secretagogues, whereas taxol caused a small
      inhibition of IS that is partly ascribed to a decrease in [Ca(2+)](c). When
      [Ca(2+)](c) was elevated and controlled by KCl or tolbutamide, the amplifying
      action of glucose was unaffected by microtubule disruption or stabilization. Both
      phases of IS were larger in response to glucose than tolbutamide, although
      triggering [Ca(2+)](c) was lower. This difference, due to amplification,
      persisted in nocodazole- or taxol-treated islets, even when IS was augmented
      fourfold by microfilament disruption with cytochalasin B or latrunculin B. In
      conclusion, metabolic amplification rapidly augments first and second phases of
      IS independently of insulin granule translocation along microtubules. We
      therefore extend our previous proposal that it does not implicate the
      cytoskeleton but corresponds to acceleration of the priming process conferring
      release competence to insulin granules.

PMID- 21178108
TI  - Hypoxia. 4. Hypoxia and ion channel function.
AB  - The ability to sense and respond to oxygen deprivation is required for survival;
      thus, understanding the mechanisms by which changes in oxygen are linked to cell
      viability and function is of great importance. Ion channels play a critical role
      in regulating cell function in a wide variety of biological processes, including
      neuronal transmission, control of ventilation, cardiac contractility, and control
      of vasomotor tone. Since the 1988 discovery of oxygen-sensitive potassium
      channels in chemoreceptors, the effect of hypoxia on an assortment of ion
      channels has been studied in an array of cell types. In this review, we describe
      the effects of both acute and sustained hypoxia (continuous and intermittent) on
      mammalian ion channels in several tissues, the mode of action, and their
      contribution to diverse cellular processes.

PMID- 21178112
TI  - Diseased renal glomeruli are getting soft. Focus on "Biophysical properties of
      normal and diseased renal glomeruli".

PMID- 21178113
TI  - Burkholderia cenocepacia O polysaccharide chain contributes to caspase-1
      dependent IL-1beta production in macrophages.
AB  - Burkholderia cenocepacia infections in CF patients involve heightened
      inflammation, fatal sepsis, and high antibiotic resistance. Proinflammatory IL
      1beta secretion is important in airway inflammation and tissue damage. However,
      little is known about this pathway in macrophages upon B. cenocepacia infection.
      We report here that murine macrophages infected with B. cenocepacia K56-2 produce
      proinflammatory cytokine IL-1beta in a TLR4 and caspase-1-mediated manner. We
      also determined that the OPS (O antigen) of B. cenocepacia LPS contributes to IL
      1beta production and pyroptotic cell death. Furthermore, we showed that the
      malfunction of the CFTR channel augmented IL-1beta production upon B. cenocepacia
      infection of murine macrophages. Taken together, we identified eukaryotic and
      bacterial factors that contribute to inflammation during B. cenocepacia
      infection, which may aid in the design of novel approaches to control pulmonary
      inflammation.

PMID- 21178114
TI  - TLR engagement prior to virus infection influences MHC-I antigen presentation in
      an epitope-dependent manner as a result of nitric oxide release.
AB  - Microorganisms contain PAMPs that can interact with different TLR-Ls. Cooperative
      signals from these receptors may modify innate and adaptive immune responses to
      invading pathogens. Therefore, a better understanding of the role TLRs play in
      initiating host defense during infections requires assessing the influence of
      multiple TLR engagement on pAPC activation and antigen presentation. In this
      study, we investigated the effects of combined TLR2, TLR3, or TLR4 engagement on
      DC activation and the presentation of LCMV antigens focusing on the major
      epitopes derived from NP and GP proteins encoded by the virus. Our results
      demonstrate that combined TLR ligation affected antigen presentation of NP(205
      212), GP(33-41), and GP(276-286), but not NP(396-404). The altered antigen
      presentation was associated with changes in proteasomal activities and NO
      production as a result of TLR engagement. Taken together, the data demonstrate
      that combined TLR ligation could result in changes of innate effectors that may
      directly influence the adaptive immune response.

PMID- 21178116
TI  - What constitutes an episode in episodic memory?
AB  - The idea of episodic memory implies the existence of a process that segments
      experience into episodes so that they can be stored in memory. It is therefore
      surprising that the link between event segmentation and the organization of
      experiences into episodes in memory has not been addressed. We found that after
      participants read narratives containing temporal event boundaries at varying
      locations in the narrative, their long-term associative memory for information
      across event boundaries was lower than their memory for information within an
      event. This suggests that event segmentation during encoding resulted in
      segmentation of those same events in memory. Further, functional imaging data
      revealed that, across participants, brain activity consistent with the ongoing
      integration of information within events correlated with this pattern of mnemonic
      segmentation. These data are the first to address the mechanisms that support the
      organization of experiences into episodes in long-term memory.

PMID- 21178115
TI  - Nitric oxide controls an inflammatory-like Ly6C(hi)PDCA1+ DC subset that
      regulates Th1 immune responses.
AB  - Using NOS2 KO mice, we investigated the hypothesis that NO modulation of BM-DC
      contributes to the NO-mediated control of Th1 immune responses. BM-DCs from NOS2
      KO mice, compared with WT BM-DCs, have enhanced survival and responsiveness to
      TLR agonists, develop more Ly6C(hi)PDCA1(+) DCs that resemble inflammatory DCs
      and produce high levels of inflammatory cytokines. Also, compared with WT
      infected mice, NOS2 KO mice infected with WNV showed enhanced expansion of a
      similar inflammatory Ly6C(hi)PDCA1(+) DC subset. Furthermore, in contrast to WT
      DCs, OVA-loaded NOS2 KO BM-DCs promoted increased IFN-gamma production by OTII
      CD4(+) T cells in vitro and when adoptively transferred in vivo. The addition of
      a NO donor to NOS2 KO BM-DCs prior to OTII T cells priming in vivo was sufficient
      to revert Th1 immune responses to levels induced by WT BM-DCs. Thus, autocrine NO
      effects on maturation of inflammatory DCs and on DC programming of T cells may
      contribute to the protective role of NO in autoimmune diseases and infections.
      Regulating NO levels may be a useful tool to shape beneficial immune responses
      for DC-based immunotherapy.

PMID- 21178117
TI  - Pessan et al. (2010) failed to recognize several important aspects.

PMID- 21178119
TI  - Epigenetic mechanisms in inflammation.
AB  - Epigenetic modifications occur in response to environmental changes and play a
      fundamental role in gene expression following environmental stimuli. Major
      epigenetic events include methylation and acetylation of histones and regulatory
      factors, DNA methylation, and small non-coding RNAs. Diet, pollution, infections,
      and other environmental factors have profound effects on epigenetic modifications
      and trigger susceptibility to diseases. Despite a growing body of literature
      addressing the role of the environment on gene expression, very little is known
      about the epigenetic pathways involved in the modulation of inflammatory and anti
      inflammatory genes. This review summarizes the current knowledge about epigenetic
      control mechanisms during the inflammatory response.

PMID- 21178120
TI  - Mapping of the human testicular proteome and its relationship with that of the
      epididymis and spermatozoa.
AB  - The testis produces male gametes in the germinal epithelium through the
      development of spermatogonia and spermatocytes into spermatids and immature
      spermatozoa with the support of Sertoli cells. The flow of spermatozoa into the
      epididymis is aided by testicular secretions. In the epididymal lumen,
      spermatozoa and testicular secretions combine with epididymal secretions that
      promote sperm maturation and storage. We refer to the combined secretions in the
      epididymis as the sperm-milieu. With two-dimensional-PAGE matrix-assisted laser
      desorption ionization time-of-flight MS analysis of healthy testes from fertile
      accident victims, 725 unique proteins were identified from 1920 two-dimensional
      gel spots, and a corresponding antibody library was established. This revealed
      the presence of 240 proteins in the sperm-milieu by Western blotting and the
      localization of 167 proteins in mature spermatozoa by ICC. These proteins, and
      those from the epididymal proteome (Li et al. 2010), form the proteomes of the
      sperm-milieu and the spermatozoa, comprising 525 and 319 proteins, respectively.
      Individual mapping of the 319 sperm-located proteins to various testicular cell
      types by immunohistochemistry suggested that 47% were intrinsic sperm proteins
      (from their presence in spermatids) and 23% were extrinsic sperm proteins,
      originating from the epididymis and acquired during maturation (from their
      absence from the germinal epithelium and presence in the epididymal tissue and
      sperm-milieu). Whereas 408 of 525 proteins in the sperm-milieu proteome were
      previously identified as abundant epididymal proteins, the remaining 22%,
      detected by the use of new testicular antibodies, were more likely to be minor
      proteins common to the testicular proteome, rather than proteins of testicular
      origin added to spermatozoa during maturation in the epididymis. The
      characterization of the sperm-milieu proteome and testicular mapping of the sperm
      located proteins presented here provide the molecular basis for further studies
      on the production and maturation of spermatozoa. This could be the basis of
      development of diagnostic markers and therapeutic targets for infertility or
      targets for male contraception.

PMID- 21178122
TI  - Regulation of hepatic cholesterol biosynthesis by berberine during
      hyperhomocysteinemia.
AB  - Hyperhomocysteinemia, an elevation of blood homocysteine levels, is a metabolic
      disorder associated with dysfunction of multiple organs. We previously
      demonstrated that hyperhomocysteinemia stimulated hepatic 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase leading to hepatic lipid
      accumulation and liver injury. The liver plays an important role in cholesterol
      biosynthesis and overall homeostasis. HMG-CoA reductase catalyzes the rate
      limiting step in cholesterol biosynthesis. Hepatic HMG-CoA reductase is a major
      target for lowering cholesterol levels in patients with hypercholesterolemia. The
      aim of the present study was to examine the effect of berberine, a plant-derived
      alkaloid, on hepatic cholesterol biosynthesis in hyperhomocysteinemic rats and to
      identify the underlying mechanism. Hyperhomocysteinemia was induced in Sprague
      Dawley rats by feeding a high-methionine diet for 4 wk. HMG-CoA reductase
      activity was markedly elevated in the liver of hyperhomocysteinemic rats, which
      was accompanied by hepatic lipid accumulation. Activation of HMG-CoA reductase
      was caused by an increase in its gene expression and a reduction in its
      phosphorylation (an inactive form of the enzyme). Treatment of
      hyperhomocysteinemic rats with berberine for 5 days inhibited HMG-CoA reductase
      activity and reduced hepatic cholesterol content. Such an inhibitory effect was
      mediated by increased phosphorylation of HMG-CoA reductase. Berberine treatment
      also improved liver function. These results suggest that berberine regulates
      hepatic cholesterol biosynthesis via increased phosphorylation of HMG-CoA
      reductase. Berberine may be therapeutically useful for the management of
      cholesterol homeostasis.

PMID- 21178121
TI  - Activation of CaMKII and ERK1/2 contributes to the time-dependent potentiation of
      Ca2+ response elicited by repeated application of capsaicin in rat DRG neurons.
AB  - When capsaicin is applied repeatedly to dorsal root ganglion (DRG) neurons for
      brief periods (10-15 s) at short intervals (5-10 min), the evoked responses
      rapidly decline, a phenomenon termed tachyphylaxis. In addition to this
      phenomenon, the present study using Ca(2+) imaging revealed that repeated
      application of capsaicin to rat dissociated DRG neurons at longer intervals (20
      40 min) or during multiple applications at short intervals elicited an
      enhancement of the responses, termed potentiation. The potentiation occurred in
      50-60% of the capsaicin-responsive cells, on average representing a 20- to 30%
      increase in the peak amplitude of the Ca(2+) signal, and was maximal at a 40-min
      application interval. An analysis of the mechanisms underlying potentiation
      revealed that it was suppressed by block of Ca(2+)/calmodulin-dependent protein
      kinase II (CaMKII) with 5 MUM KN-93 or block of the activation of extracellular
      signal-regulated kinase (ERK) 1/2 with 2 MUM U-0126. Lowering the extracellular
      Ca(2+) concentration from 2 to 1 mM or pretreatment with deltamethrin (1 MUM),
      which blocks calcineurin and tachyphylaxis, enhanced potentiation. Potentiation
      was not affected by: 1) inhibition of protein kinase C or protein kinase A, 2)
      block of the three subtypes of neurokinin receptors, or 3) block of the
      trafficking of transient receptor potential V1 channel to the membrane. These
      results indicate that the potentiation is a slowly developing Ca(2+)-modulated
      process that is mediated by a complex intracellular signaling pathway involving
      activation of CaMKII and ERK1/2. Potentiation may be an important peripheral
      autosensitization mechanism that occurs independently of the pronociceptive
      effects of inflammatory mediators and neurotrophic factors.

PMID- 21178123
TI  - Glycerol-induced fluid shifts attenuate the vestibulosympathetic reflex in
      humans.
AB  - The glycerol dehydration test (GDT) has been used to test for the presence of
      Meniere's disease and elicits acute alterations in vestibular reflexes in both
      normal and pathological states. Activation of the vestibulosympathetic reflex
      (VSR) increases muscle sympathetic nerve activity (MSNA) and peripheral vascular
      resistance. We hypothesized that the GDT would attenuate the VSR through fluid
      shifts of the inner ear. Sixteen male subjects (26 +/- 1 yr) were randomly
      assigned to be administered either glycerol mixed with cranberry juice (97 +/- 3
      ml glycerol + equal portion of cranberry juice; n = 9) or a placebo control
      [water + cranberry juice (100 ml each); n = 7]. Subjects in both groups performed
      head-down rotation (HDR), which engages the VSR, before and after administration
      of either the glycerol or placebo. MSNA (microneurography), arterial blood
      pressure, and leg blood flow (venous occlusion plethysmography) were measured
      during HDR. Before glycerol administration, HDR significantly increased MSNA
      burst frequency (Delta8 +/- 1 bursts/min; P < 0.01) and total activity (Delta77
      +/- 18%; P < 0.01) and decreased calf vascular conductance (-Delta20 +/- 3%; P <
      0.01). However, HDR performed postadministration of glycerol resulted in an
      attenuated MSNA increase (Delta3 +/- 1 bursts/min, Delta22 +/- 3% total activity)
      and decrease in calf vascular conductance (-Delta7 +/- 4%). HDR significantly
      increased MSNA burst frequency (Delta5 +/- 1 and Delta5 +/- 2 bursts/min) and
      total activity (Delta58 +/- 13% and Delta52 +/- 18%) in the placebo group before
      and after placebo, respectively (P < 0.01). Likewise, decreases in calf vascular
      conductance during HDR before and after placebo were not different (-Delta13 +/-
      4% and -Delta14 +/- 2%, respectively; P < 0.01). These results suggest that fluid
      shifts of the inner ear via glycerol dehydration attenuate the VSR. These data
      provide support that inner ear fluid dynamics can have a significant impact on
      blood pressure regulation via the VSR in humans.

PMID- 21178124
TI  - Temporal phasing of locomotor activity, heart rate rhythmicity, and core body
      temperature is disrupted in VIP receptor 2-deficient mice.
AB  - Neurons of the brain's biological clock located in the hypothalamic
      suprachiasmatic nucleus (SCN) generate circadian rhythms of physiology (core body
      temperature, hormone secretion, locomotor activity, sleep/wake, and heart rate)
      with distinct temporal phasing when entrained by the light/dark (LD) cycle. The
      neuropeptide vasoactive intestinal polypetide (VIP) and its receptor (VPAC2) are
      highly expressed in the SCN. Recent studies indicate that VIPergic signaling
      plays an essential role in the maintenance of ongoing circadian rhythmicity by
      synchronizing SCN cells and by maintaining rhythmicity within individual neurons.
      To further increase the understanding of the role of VPAC2 signaling in circadian
      regulation, we implanted telemetric devices and simultaneously measured core body
      temperature, spontaneous activity, and heart rate in a strain of VPAC2-deficient
      mice and compared these observations with observations made from mice examined by
      wheel-running activity. The study demonstrates that VPAC2 signaling is necessary
      for a functional circadian clock driving locomotor activity, core body
      temperature, and heart rate rhythmicity, since VPAC2-deficient mice lose the
      rhythms in all three parameters when placed under constant conditions (of either
      light or darkness). Furthermore, although 24-h rhythms for three parameters are
      retained in VPAC2-deficient mice during the LD cycle, the temperature rhythm
      displays markedly altered time course and profile, rising earlier and peaking ~4
      6 h prior to that of wild-type mice. The use of telemetric devices to measure
      circadian locomotor activity, temperature, and heart rate, together with the
      classical determination of circadian rhythms of wheel-running activity, raises
      questions about how representative wheel-running activity may be of other
      behavioral parameters, especially when animals have altered circadian phenotype.

PMID- 21178125
TI  - ACE2/ANG-(1-7)/Mas pathway in the brain: the axis of good.
AB  - The last decade has seen the discovery of several new components of the renin
      angiotensin system (RAS). Among them, angiotensin converting enzyme-2 (ACE2) and
      the Mas receptor have forced a reevaluation of the original cascade and led to
      the emergence of a new arm of the RAS: the ACE2/ANG-(1-7)/Mas axis. Accordingly,
      the new system is now seen as a balance between a provasoconstrictor,
      profibrotic, progrowth axis (ACE/ANG-II/AT(1) receptor) and a provasodilatory,
      antifibrotic, antigrowth arm (ACE2/ANG-(1-7)/Mas receptor). Already, this
      simplistic vision is evolving and new components are branching out upstream [ANG
      (1-12) and (pro)renin receptor] and downstream (angiotensin-IV and other
      angiotensin peptides) of the classical cascade. In this review, we will summarize
      the role of the ACE2/ANG-(1-7)/Mas receptor, focusing on the central nervous
      system with respect to cardiovascular diseases such as hypertension, chronic
      heart failure, and stroke, as well as neurological diseases. In addition, we will
      discuss the new pharmacological (antagonists, agonists, activators) and genomic
      (knockout and transgenic animals) tools that are currently available. Finally, we
      will review the latest data regarding the various signaling pathways downstream
      of the Mas receptor.

PMID- 21178126
TI  - Chronic estradiol exposure induces oxidative stress in the hypothalamus to
      decrease hypothalamic dopamine and cause hyperprolactinemia.
AB  - Estrogens are known to cause hyperprolactinemia, most probably by acting on the
      tuberoinfundibular dopaminergic (TIDA) system of the hypothalamus. Dopamine (DA)
      produced by TIDA neurons directly inhibits prolactin secretion and, therefore, to
      stimulate prolactin secretion, estrogens inhibit TIDA neurons to decrease DA
      production. However, the mechanism by which estrogen produces this effect is not
      clear. In the present study, we used a paradigm involving chronic exposure to low
      levels of estradiol-17beta (E(2)) to mimic prolonged exposures to environmental
      and endogenous estrogens. We hypothesized that chronic exposure to low levels of
      E(2) induces oxidative stress in the arcuate nucleus (AN) of the hypothalamus
      that contains TIDA neurons and causes nitration of tyrosine hydroxylase (TH), the
      rate-limiting enzyme in the synthesis of DA. This results in a significant
      decrease in DA and consequently, hyperprolactinemia. To investigate this, adult,
      intact female cycling rats were implanted with slow-release E(2) pellets (20
      ng/day) for 30, 60, or 90 days and were compared with old (16-18 mo old) constant
      estrous (OCE) rats. Chronic E(2) exposure significantly increased the expression
      of glial fibrillary acidic protein and the concentrations of interleukin-1beta
      (IL-1beta) and nitrate in the AN that contains perikarya of TIDA neurons and
      increased nitration of TH in the median eminence (ME) that contains the
      terminals. These levels were comparable to those seen in OCE rats. We observed a
      significant decrease in DA concentrations in the ME and hyperprolactinemia in an
      exposure-dependent manner similar to that seen in OCE rats. It was concluded that
      chronic exposure to low levels of E(2) evokes oxidative stress in the AN to
      inhibit TIDA neuronal function, most probably leading to hyperprolactinemia.

PMID- 21178128
TI  - Glycerol loss to water exceeds glycerol catabolism via glycerol kinase in freeze
      resistant rainbow smelt (Osmerus mordax).
AB  - Rainbow smelt accumulate high amounts of glycerol in winter. In smelt, there is a
      predictable profile of plasma glycerol levels that starts to increase in November
      (<5 MUmol/ml), peaks in mid-February (>200 MUmol/ml), and thereafter decreases to
      reach the initial levels in the beginning of May. The aim of this study was to
      investigate the respective role of the two main mechanisms that might be involved
      in glycerol clearance from mid-February: 1) breakdown of glycerol to glycerol-3
      phosphate through the action of the glycerol kinase (GK) and 2) direct loss
      toward the environment. Over the entire glycerol cycle, loss to water represents
      a daily loss of ~10% of the total glycerol content of fish. GK activities were
      very low in all tissues investigated and likely have a minor quantitative role in
      the glycerol cycle. These results suggest that glycerol levels are dictated by
      the rate of glycerol synthesis (accelerated and deactivated during the
      accumulation and decrease stages, respectively). Although not important in
      glycerol clearance, GK in liver might have an important metabolic function for
      other purposes, such as gluconeogenesis, as evidenced by the significant increase
      of activity at the end of the cycle.

PMID- 21178127
TI  - Hemodynamic responses to heat stress in the resting and exercising human leg:
      insight into the effect of temperature on skeletal muscle blood flow.
AB  - Heat stress increases limb blood flow and cardiac output (Q) in humans,
      presumably in sole response to an augmented thermoregulatory demand of the skin
      circulation. Here we tested the hypothesis that local hyperthermia also increases
      skeletal muscle blood flow at rest and during exercise. Hemodynamics, blood and
      tissue oxygenation, and muscle, skin, and core temperatures were measured at rest
      and during exercise in 11 males across four conditions of progressive whole body
      heat stress and at rest during isolated leg heat stress. During whole body heat
      stress, leg blood flow (LBF), Q, and leg (LVC) and systemic vascular conductance
      increased gradually with elevations in muscle temperature both at rest and during
      exercise (r(2) = 0.86-0.99; P < 0.05). Enhanced LBF and LVC were accompanied by
      reductions in leg arteriovenous oxygen (a-vO(2)) difference and increases in deep
      femoral venous O(2) content and quadriceps tissue oxygenation, reflecting
      elevations in muscle and skin perfusion. The increase in LVC occurred despite an
      augmented plasma norepinephrine (P < 0.05) and was associated with elevations in
      muscle temperature (r(2) = 0.85; P = 0.001) and arterial plasma ATP (r(2) = 0.87;
      P < 0.001). Isolated leg heat stress accounted for one-half of the increase in
      LBF with severe whole body heat stress. Our findings suggest that local
      hyperthermia also induces vasodilatation of the skeletal muscle microvasculature,
      thereby contributing to heat stress and exercise hyperemia. The increased limb
      muscle vasodilatation in these conditions of elevated muscle sympathetic
      vasoconstrictor activity is closely related to the rise in arterial plasma ATP
      and local tissue temperature.

PMID- 21178129
TI  - Older type 2 diabetic males do not exhibit abnormal pulmonary oxygen uptake and
      muscle oxygen utilization dynamics during submaximal cycling exercise.
AB  - There are reports of abnormal pulmonary oxygen uptake (Vo(2)) and deoxygenated
      hemoglobin ([HHb]) kinetics in individuals with Type 2 diabetes (T2D) below 50 yr
      of age with disease durations of <5 yr. We examined the Vo(2) and muscle [HHb]
      kinetics in 12 older T2D patients with extended disease durations (age: 65 +/- 5
      years; disease duration 9.3 +/- 3.8 years) and 12 healthy age-matched control
      participants (CON; age: 62 +/- 6 years). Maximal oxygen uptake (Vo(2max)) was
      determined via a ramp incremental cycle test and Vo(2) and [HHb] kinetics were
      determined during subsequent submaximal step exercise. The Vo(2max) was
      significantly reduced (P < 0.05) in individuals with T2D compared with CON (1.98
      +/- 0.43 vs. 2.72 +/- 0.40 l/min, respectively) but, surprisingly, Vo(2) kinetics
      was not different in T2D compared with CON (phase II time constant: 43 +/- 17 vs.
      41 +/- 12 s, respectively). The Delta[HHb]/DeltaVo(2) was significantly higher in
      T2D compared with CON (235 +/- 99 vs. 135 +/- 33 AU.l(-1).min(-1); P < 0.05).
      Despite a lower Vo(2max), Vo(2) kinetics is not different in older T2D compared
      with healthy age-matched control participants. The elevated Delta[HHb]/DeltaVo(2)
      in T2D individuals possibly indicates a compromised muscle blood flow that
      mandates a greater O(2) extraction during exercise. Longer disease duration may
      result in adaptations in the O(2) extraction capabilities of individuals with
      T2D, thereby mitigating the expected age-related slowing of Vo(2) kinetics.

PMID- 21178130
TI  - Advancing translational research collaborations.
AB  - In February 2010, the U.S. National Institutes of Health (NIH) sponsored a
      national Clinical and Translational Science Awards forum titled "Promoting
      Efficient and Effective Collaborations among Academia, Government and Industry."
      This forum brought together a broad set of stakeholders who were charged with
      developing a path for promoting such partnerships. Here, we describe key issues
      discussed at the forum and plans for moving forward with this ambitious agenda.

PMID- 21178131
TI  - 2010: awards show what translation can accomplish.

PMID- 21178132
TI  - Training the translational scientist.
AB  - A Clinical and Translational Science Awards Industry Forum titled "Promoting
      Efficient and Effective Collaborations Among Academia, Government, and Industry"
      was held in February 2010. A session at this forum was organized to address the
      training and skills needed to develop a biomedical scientific workforce that
      interfaces academia, government agencies, and industry to support the process of
      translating science into applicable means to improve health. By examining the
      requisite competencies and training resources for scientists in each of these
      sectors, opportunities for collaboration and adoption of new educational
      strategies were identified that could help to address barriers to translational
      research education and career development.

PMID- 21178133
TI  - Collaborations among academia, government, and industry in the diagnostics space:
      barriers and some ideas for solutions.
AB  - The development and commercialization of diagnostic assays is distinct from that
      of therapeutic drugs in many important respects; for example, there are more
      variable regulatory requirements and reduced outside investments for diagnostics.
      The diagnostics industry has a pro-collaborative stance, because there is
      considerable mutual benefit in working in partnership with university or
      government researchers. However, there are substantial barriers to industry
      academic collaborations. A Clinical and Translational Science Awards Industry
      Forum titled "Promoting Efficient and Effective Collaborations Among Academia,
      Government, and Industry" was held in February 2010, and a session at this forum
      was organized to list some of the most important barriers to diagnostics
      development and to discuss some possible solutions.

PMID- 21178134
TI  - Development of the first inhaled antibiotic for the treatment of cystic fibrosis.
AB  - Tobramycin Inhalation Solution USP (TOBI), a therapy developed to treat lung
      infections associated with cystic fibrosis (CF), was presented as a demonstration
      case for collaborative pharmaceutical development at a Clinical and Translational
      Science Awards Industry Forum on "Promoting Efficient and Effective
      Collaborations Among Academia, Government, and Industry" held in February 2010.
      TOBI was developed by PathoGenesis Corporation (Seattle, WA) in collaboration
      with the academic inventors, the National Institutes of Health, the U.S. Food and
      Drug Administration, and the CF Foundation. The presenters, representing the
      academic, industry, and foundation partners, each reviewed the program from their
      perspectives and identified challenges that existed during the discovery,
      development, and commercialization of TOBI. The attendees were asked to consider
      other collaborative opportunities that might have further improved TOBI
      development, including the optimal roles of the academic researchers,
      foundations, and other agencies when industry drives development and
      commercialization decisions.

PMID- 21178135
TI  - Working with the CTSA Consortium: what we bring to the table.
AB  - In 2006, the National Institutes of Health (NIH) initiated the Clinical and
      Translational Science Awards (CTSA) program to establish premier academic sites
      designed to enhance the efficiency and effectiveness of translational research at
      the local, regional, and national levels. In February 2010, the NIH sponsored a
      national CTSA forum on "Promoting Efficient and Effective Collaborations Among
      Academia, Government, and Industry." This forum brought together a broad set of
      stakeholders who were charged with developing a path for promoting such
      partnerships. One theme, discussed in this meeting report, focused on
      opportunities and approaches to leverage CTSA institutions as a consortium in
      fostering public-private partnerships.

PMID- 21178136
TI  - Academic/Industry challenges for medical device development.
AB  - A Clinical and Translational Science Awards Industry Forum titled "Promoting
      Efficient and Effective Collaborations Among Academia, Government, and Industry"
      was held in February 2010. A workshop at this forum was organized to discuss ways
      to promote medical device innovation. Specific challenges to the device
      development process were identified, as well as practical ways to address some of
      these issues.

PMID- 21178138
TI  - Short-term monotherapy in HIV-infected patients with a virus entry inhibitor
      against the gp41 fusion peptide.
AB  - To infect host cells, most enveloped viruses must insert a hydrophobic fusion
      peptide into the host cell membrane. Thus, fusion peptides may be valuable
      targets for developing drugs that block virus entry. We have shown previously
      that a natural 20-residue fragment of alpha(1)-antitrypsin, designated VIRus
      Inhibitory Peptide (VIRIP), that binds to the gp41 fusion peptide of HIV-1
      prevents the virus from entering target cells in vitro. Here, we examine the
      efficacy of 10-day monotherapy with the optimized VIR-576 derivative of VIRIP in
      treatment-naive, HIV-1-infected individuals with viral RNA loads of >=10,000
      copies per ml. We report that at the highest dose (5.0 grams per day),
      intravenous infusion of VIR-576 reduced the mean plasma viral load by 1.23
      log(10) copies per ml without causing severe adverse effects. Our results are
      proof of concept that fusion peptide inhibitors suppress viral replication in
      human patients, and offer prospects for the development of a new class of drugs
      that prevent virus particles from anchoring to and infecting host cells.

PMID- 21178137
TI  - Calreticulin is the dominant pro-phagocytic signal on multiple human cancers and
      is counterbalanced by CD47.
AB  - Under normal physiological conditions, cellular homeostasis is partly regulated
      by a balance of pro- and anti-phagocytic signals. CD47, which prevents cancer
      cell phagocytosis by the innate immune system, is highly expressed on several
      human cancers including acute myeloid leukemia, non-Hodgkin's lymphoma, and
      bladder cancer. Blocking CD47 with a monoclonal antibody results in phagocytosis
      of cancer cells and leads to in vivo tumor elimination, yet normal cells remain
      mostly unaffected. Thus, we postulated that cancer cells must also display a
      potent pro-phagocytic signal. Here, we identified calreticulin as a pro
      phagocytic signal that was highly expressed on the surface of several human
      cancers, but was minimally expressed on most normal cells. Increased CD47
      expression correlated with high amounts of calreticulin on cancer cells and was
      necessary for protection from calreticulin-mediated phagocytosis. Blocking the
      interaction of target cell calreticulin with its receptor, low-density
      lipoprotein receptor-related protein, on phagocytic cells prevented anti-CD47
      antibody-mediated phagocytosis. Furthermore, increased calreticulin expression
      was an adverse prognostic factor in diverse tumors including neuroblastoma,
      bladder cancer, and non-Hodgkin's lymphoma. These findings identify calreticulin
      as the dominant pro-phagocytic signal on several human cancers, provide an
      explanation for the selective targeting of tumor cells by anti-CD47 antibody, and
      highlight the balance between pro- and anti-phagocytic signals in the immune
      evasion of cancer.

PMID- 21178139
TI  - The efficacy, sensitivity, and specificity of strip meniscometry in conjunction
      with tear function tests in the assessment of tear meniscus.
AB  - PURPOSE: To evaluate the specificity and sensitivity of strip meniscometry (SM)
      testing in conjunction with tear function tests in the diagnosis of dry eye (DE)
      disease and to investigate the effect of SM on reflex tearing. METHODS: One
      hundred seven left eyes of 107 patients with definite DE disease according to the
      Japanese DE diagnostic criteria and 68 left eyes of 68 age- and sex-matched
      control subjects were studied. Tear meniscus height (TMH) measurements,
      fluorescein tear film break-up time (FTBUT), fluorescein (F) and rose bengal (RB)
      staining, and Schirmer's test-1 (ST) were also performed. The assessment of
      reflex tearing before and after SM application was assessed with a graticule
      scale at the slit lamp and by optical coherence tomography. The sensitivity and
      specificity of SM alone and in combination with tear function tests were also
      sought. RESULTS: The SM scores, TMH measurements, FTBUTs, and STs were
      significantly lower in dry eye patients than in the controls (P < 0.001). The RB
      and F staining scores were significantly higher in the dry eye group than in the
      control group (P < 0.001). The meniscometry strips did not induce significant
      changes in relation to reflex tearing. SM had an acceptable sensitivity and
      specificity. CONCLUSIONS: SM is a swift, noninvasive, promising method of
      assessing tear meniscus volume. The combined SM and FTBUT examination appears to
      be a sensitive approach to the assessment of dry eye disease.

PMID- 21178140
TI  - Selective blockade of cytoskeletal actin remodeling reduces experimental
      choroidal neovascularization.
AB  - PURPOSE: The efficacy of the peptide Ac-EEED on reducing cell adhesion and
      proliferation in vitro and choroidal neovascularization (CNV) in vivo was
      examined. METHODS: The peptide chimera containing the Ac-EEED sequence was
      chemically linked to the N terminus of the XMTM delivery peptide from the E(rns)
      viral surface protein. Ac-EEED or scrambled control peptide (SCRAM) was added to
      cultures of vascular smooth muscle cells, pericytes, endothelial cells, and
      fibroblasts, and adhesion, growth, and matrix production was assessed. Ac-EEED or
      SCRAM was injected into the vitreous of mice undergoing laser rupture of Bruch's
      membrane to induce CNV and lesion volume, neovascularization and lesion fibrosis
      were assessed. RESULTS: Ac-EEED-induced changes in the morphology of the actin
      cytoskeleton by inhibiting polymerization of G-actin and disrupting the formation
      of stress fibers. Pretreatment with Ac-EEED resulted in endothelial cells
      becoming less responsive to the mitogenic and pro-adhesive effects of VEGF. Ac
      EEED treatment in fibroblasts reduced TGF-beta-induced fibrosis as assessed by
      decreased levels of connective tissue growth factor, cysteine-rich 61, collagen I
      (COL1A2), and collagen III (COL3A1). CNV lesion size and fibrosis were reduced in
      a concentration-dependent manner by up to 60%. CONCLUSIONS: In vitro studies
      showed that Ac-EEED affects a broad range of mechanical properties associated
      with cytoskeletal actin to reduce growth factor effects. The utilization of Ac
      EEED in vivo may offer a novel therapeutic strategy by both suppressed neovessel
      growth and curtailing fibrosis typically associated with the involutional stage
      of CNV.

PMID- 21178142
TI  - Corneal endothelial toxicity of air and SF6.
AB  - PURPOSE: The authors conducted in vivo assessment of corneal endothelial toxicity
      of air and SF6 in the feline model. This research was motivated by the increased
      use of air in anterior segment surgery in human subjects. METHODS: This was a
      prospective masked study. The eyes of 16 healthy adult cats were randomly
      assigned for the injection of 0.7 mL air into the anterior chamber of one eye and
      SF6 in the contralateral eye. Daily examination included slit lamp photographs,
      pachymetry, and tonometry. Specular microscopy was performed before, 7 days
      after, and 10 days after injection. The animals were euthanatized, and the
      corneas were processed for alizarin red-trypan blue staining and for light and
      electron microscopy. RESULTS: SF6 remained in the anterior chamber significantly
      longer than air. Both groups showed postinjection inflammation, which on average
      was maximal at day 2 and more severe with SF6. No difference in IOP was observed
      between the two groups. Specular microscopy showed significant endothelial cell
      loss in the SF6 group (mean postinjection cell loss, 132 +/- 50 cells/mm(2)) but
      not in the group injected with air. Alizarin red staining revealed significant
      regional differences in cell density only in the SF6 group and more pronounced
      endothelial cell loss in the superior area. CONCLUSIONS: These results indicate
      that both air and SF6 injected into the anterior chamber of the eye can induce
      intraocular reaction in the feline model and that SF6 is more toxic than air in
      terms of endothelial cell loss and anterior chamber inflammation.

PMID- 21178143
TI  - Bacterial infection in scarring trachoma.
AB  - PURPOSE: To assess whether non-chlamydial bacterial infection is associated with
      trachomatous scarring in adults. METHODS: This was a case-control study of 360
      cases with trachomatous scarring but without trichiasis, and 360 controls without
      scarring. All participants underwent clinical examination, and a swab was taken
      from the inferior conjunctival fornix. Samples were inoculated onto blood and
      chocolate agar later that day. RESULTS: Bacterial isolates were identified in
      54.0% of cases compared with 34.6% of controls (P < 0.001). A multivariate
      logistic regression model adjusted for age and lack of education showed that
      scarring was associated with the presence of commensal organisms (odds ratio
      [OR], 1.46; 95% confidence interval [CI], 1.01-2.09) and was strongly associated
      with the presence of pathogenic organisms (OR, 4.08; 95% CI, 1.59-10.45). There
      was an increasing prevalence of all bacterial isolates with increasing severity
      of scarring (P(trend) < 0.001). CONCLUSIONS: Trachomatous scarring is strongly
      associated with non-chlamydial bacterial infection compared with controls. The
      role of such infection with regard to scarring progression should be investigated
      and may have important implications for trachoma control strategies and
      prevention of blindness.

PMID- 21178144
TI  - The Impact of Vision Impairment for Children (IVI_C): validation of a vision
      specific pediatric quality-of-life questionnaire using Rasch analysis.
AB  - PURPOSE: To validate the Impact of Vision Impairment for Children (the IVI_C), a
      new vision-specific pediatric instrument designed to assess the affect of
      impaired vision on quality of life (QoL) in children. METHODS: The IVI_C was
      administered to vision-impaired and normally sighted students, 8 to 18 years of
      age. Reliability and validity were tested, and the IVI_C was subjected to Rasch
      analysis to assess the scale unidimensionality, measurement characteristics,
      response options, and targeting. RESULTS: The mean (SD) presenting bilateral
      distance visual acuity (VA) for the vision-impaired group (n = 122) was 1.10
      (0.79) logMAR and 1.15 (0.80) logMAR for near VA. After the initial response
      categories were collapsed from five to three, content validity was further
      supported by good person and item fit parameters. The person separation index
      (PSI) was 0.85, which indicates that the IVI_C can assess QoL across children of
      several participation levels. The scale was shown to be unidimensional after
      principal components analysis (PCA) of the residuals (t-test; P = 0.48, P =
      0.34). Significant differences in overall person measures between the vision
      impaired and normally sighted groups substantiated the scale discriminant
      validity (ANOVA; F = 78.75; P < 0.0001). Guttman split-half correlations for
      temporal, mode (face-to-face and telephone), and interobserver administrations
      were 0.95, 0.90, and 0.86, respectively, supporting scale reliability.
      CONCLUSIONS: The modified IVI_C is a unidimensional, reliable, and valid scale
      for assessing QoL of children with vision impairment. It provides a valid means
      of assessing the outcomes of interventions and needs in children with vision
      impairment.

PMID- 21178141
TI  - Significance of outer blood-retina barrier breakdown in diabetes and ischemia.
AB  - PURPOSE: The outer blood-retina barrier (BRB) separates the neural retina from
      the choroidal vasculature, which is responsible for approximately 80% of blood
      supplies in the eye. To determine the significance of outer BRB breakdown in
      diabetic retinopathy, the outer BRB-specific leakage of macromolecules in
      diabetic and ischemic rodents was investigated. METHODS: Diabetes and ischemia
      were induced in rodents by streptozotocin and oxygen-induced retinopathy,
      respectively. Diabetic and ischemic rodents were injected intravenously with
      fluorescein isothiocyanate (FITC)-dextran. The outer BRB-specific leakage in
      diabetic and ischemic rodents was visualized by fluorescent microscopy. RESULTS:
      A microscopic imaging assay was developed to examine outer BRB breakdown. The
      outer BRB-specific leakage of fluorescent macromolecules was visualized in
      diabetic and ischemic rodents. Substantial leakages of macromolecules through the
      outer BRB in diabetic and ischemic rodents were detected with this assay. The
      number of severe outer BRB leakage sites is inversely proportional to the size of
      macromolecules. Significant depletion of occludin in the RPE of ischemic and
      diabetic rodents was also observed. CONCLUSIONS: For the first time, a
      microscopic imaging assay for directly visualizing macromolecules leaked through
      the outer BRB in rodents was developed. Using this assay, the authors
      demonstrated the significance of outer BRB breakdown in diabetes and ischemia,
      which will have implications to the understanding, diagnosis, and treatment of
      diabetic macular edema and other ocular diseases with outer BRB defects. The
      microscopic imaging assay established in this study will likely be very useful to
      the development of drugs for macular edema.

PMID- 21178145
TI  - Isolation and propagation of mesenchymal stem cells from the lacrimal gland.
AB  - PURPOSE: Previously, it was reported that the murine lacrimal gland is capable of
      repair after experimentally induced injury and that the number of stem/progenitor
      cells was increased during the repair phase (2-3 days after injury). The aim of
      the present study was to determine whether these cells can be isolated from the
      lacrimal gland and propagated in vitro. METHODS: Lacrimal gland injury was
      induced by injection of interleukin (IL)-1, and injection of saline vehicle
      served as control. Two and half days after injection, the lacrimal glands were
      removed and used to prepare explants or acinar cells for tissue culture. Cells
      derived from the explants and the acinar cells were grown in DMEM supplemented
      with 10% fetal bovine serum. Cells were stained for the stem cells markers,
      nestin, vimentin, ABCG2, and Sca-1. Cell proliferation was measured using an
      antibody against Ki67 or a cell-counting kit. The adipogenic capability of these
      cells was also tested in vitro. RESULTS: Results show that nestin-positive cells
      can be isolated from IL-1-injected, but not saline-injected, lacrimal glands. A
      population of nestin-positive cells was also positive for vimentin, an
      intermediate filament protein expressed by mesenchymal cells. In addition,
      cultured cells expressed two other markers of stem cells, ABCG2 and Sca-1. These
      cells proliferated in vitro and can be induced to form adipocytes, attesting to
      their mesenchymal stem cell property. CONCLUSIONS: Murine lacrimal glands contain
      mesenchymal stem cells that seem to play a pivotal role in tissue repair.

PMID- 21178146
TI  - Therapeutic effect of stealth-type polymeric nanoparticles with encapsulated
      betamethasone phosphate on experimental autoimmune uveoretinitis.
AB  - PURPOSE: The therapeutic effects of betamethasone phosphate (BP) encapsulated in
      biocompatible and biodegradable blended nanoparticles of poly(lactic acid) (PLA)
      homopolymers and PEG-block-PLA copolymers (stealth nanosteroids) were examined in
      an experimental autoimmune uveoretinitis (EAU) model in Lewis rats. METHODS: EAU
      was induced by S-antigen peptide in Lewis rats. Accumulation of systemically
      administered Cy7-labeled stealth nanoparticles in inflamed eyes of rats with EAU
      was assessed using in vivo fluorescence imaging, and the therapeutic effect of
      stealth nanosteroids, nonstealth nanosteroids, or saline on EAU was examined. The
      eyes were obtained 7 days after the treatment, and the histologic score was
      determined using pathologic findings. The expression of inflammatory cytokines
      including IL-6, IL-17, and VEGF was determined immunohistochemically. RESULTS:
      Cy7-stealth nanoparticles accumulated in inflamed eyes of rats with EAU and
      remained in situ for a 3-day period. Systemically administered stealth
      nanosteroids (100 MUg of BP) reduced the clinical scores of rats with EAU within
      1 day and maintained the effect for 2 weeks. This treatment also decreased the
      histologic scores and the expression of inflammatory cytokines in the retina of
      EAU. CONCLUSIONS: The strong therapeutic benefit on EAU obtained with the stealth
      nanosteroids may have been due to prolonged blood circulation and targeting to
      the inflamed uvea and retina, in addition to sustained release in situ.

PMID- 21178147
TI  - Recruitment of blood-derived inflammatory cells mediated via tumor necrosis
      factor-alpha receptor 1b exacerbates choroidal neovascularization.
AB  - Purpose. Tumor necrosis factor (TNF)-alpha contributes to inflammation-associated
      angiogenesis, and TNF-alpha receptor 1b is selectively expressed on immuno
      competent and endothelial cells. This study investigated the role of TNF-alpha
      receptor 1b in the recruitment of circulating inflammatory cells and the
      development of choroidal neovascularization (CNV). Methods. Lethally irradiated
      Tnfrsf1b(-/-) mice and their wild-type (WT) controls were transplanted with whole
      adult bone marrow (BM) cells, competent for both TNF-alpha receptors 1a and 1b
      (gfp(+) labeled), as well as with BM cells deficient for TNF-alpha receptor 1b.
      One month after transplantation CNV was induced by laser damage of Bruch's
      membrane. Pathologic angiogenesis was estimated qualitatively and quantitatively
      by histology on choroidal flatmounts and paraffin cross sections. Macrophage
      invasion was investigated by immunochemistry. Results. One month after
      transplantation the reconstitution rate measured by FACS analysis was >80% in
      gfp(+)-chimeric mice. Two weeks after laser injury reduced gfp(+)-cell invasion
      to the laser scars and decreased pathologic angiogenesis were observed in
      Tnfrsf1b(-/-) versus WT recipients. Approximately 70% of the invaded gfp(+) cells
      were labeled with macrophage marker F4/80. Transplantation of TNF-alpha receptor
      1b-deficient BM cells in WT recipients reduced the CNV lesion compared with WT
      and Tnfrsf1b(-/-) recipients that received TNF-alpha receptor-competent BM cells.
      Transplantation of receptor 1b-deficient cells to Tnfrsf1b(-/-) recipients
      further reduced the degree of CNV formation. Conclusions. Signals through TNF
      alpha receptor 1b expressed on BM -derived inflammatory cells mediate an
      increased inflammatory cell invasion and enhanced angiogenic response after laser
      induced rupture of Bruch's membrane.

PMID- 21178149
TI  - Staphylococcus lugdunensis is the likely origin of the ornithine decarboxylase
      operon in Staphylococcus epidermidis 2015B.

PMID- 21178150
TI  - Nonpharmacologic approaches to the management of insomnia.
AB  - Insomnia is one of the more common complaints patients present to their
      physicians. Sleep problems affect up to one-third of all Americans, and the loss
      of workplace productivity and increased healthcare utilization result in costs
      approaching $100 billion a year. Patients with acute insomnia generally respond
      well to various sedative hypnotic medications, but chronic insomnia is a
      different challenge. Physicians and patients may raise concerns about the long
      term use of sedative hypnotic medications. Even in light of these concerns,
      however, the chronic insomnia remains, ostensibly leaving the physician few
      choices. A number of promising nonpharmacologic strategies are available that
      physicians can easily implement. Through the use of self-rating instruments and a
      sleep log, physicians can bring the sleep problem into better focus and monitor
      the efficacy of clinical interventions. Certain behavioral techniques, such as
      sleep hygiene, stimulus control, and sleep restriction, can be effective remedies
      for chronic insomnia. The use of cranial electric stimulation for insomnia is
      also showing promising results. Through careful assessment and the adoption of
      simple nonpharmacologic strategies, the physician's interventions may result in a
      good night's sleep.

PMID- 21178151
TI  - Primary care physicians and elder abuse: current attitudes and practices.
AB  - CONTEXT: while estimates suggest that between 1.4% and 5.4% of older adults
      experience abuse, only 1 of 14 cases of elder abuse or neglect is ever reported
      to authorities. It is critical for clinicians to be aware of elder abuse in order
      to improve primary care. OBJECTIVE: to understand Michigan primary care
      physicians' knowledge of and reporting practices for elder abuse, including the
      type of elder abuse education they received, the nature of their clinical
      practice, and the barriers that prevent them from reporting elder abuse. METHODS:
      a 17-item survey was mailed to 855 primary care physicians in Michigan in 2 waves
      between October 2007 and December 2007. RESULTS: Of the 855 surveys mailed, 222
      were returned for a response rate of 26%. The majority of physicians (131 [67%]
      of 197 physicians) believed that their training about elder abuse was not very
      adequate or not adequate at all. Physicians with fewer than 10 hours of training
      were more likely to rate their training as not adequate when compared to those
      who had more than 10 hours of clinical training (chi(2)=64.340, P<.001). Whether
      abuse was reported was highly correlated with whether it was suspected
      (chi(2)=26.195, P<.001). Those physicians who reported receiving formal training
      on the topic of elder abuse in residency programs and those who reported
      participating in CME activities while in practice were less likely to identify
      not recognizing abuse at time of patient visits as a barrier to reporting.
      CONCLUSION: recognizing the subtle signs of elder abuse continues to be a barrier
      for physicians who treat older adult patients. However, education may improve
      primary care physicians' ability to detect and recognize elder abuse.

PMID- 21178152
TI  - Survey of Attitudes and Practices of Osteopathic Primary Care Physicians
      Regarding Taking of Sexual Histories and HIV Screening.
AB  - CONTEXT: an estimated 252,000 to 312,000 individuals have undiagnosed human
      immunodeficiency virus (HIV) infection in the United States. To date, little has
      been known about osteopathic physicians' attitudes and practices regarding
      routine HIV testing. OBJECTIVES: to understand osteopathic primary care
      physicians' attitudes and practices toward HIV testing and sexual history taking
      and to examine factors associated with osteopathic physicians' recommendations of
      HIV testing at the initial patient visit. METHODS: a cross-sectional survey of
      osteopathic physicians was conducted at the 106th Annual Convention of the
      Florida Osteopathic Medical Association in February 2009. Survey participants
      were asked 36 questions about osteopathic physician and patient sociodemographic
      factors and osteopathic physician attitudes and office practices regarding HIV
      testing and sexual history taking. RESULTS: a total of 233 osteopathic physicians
      completed the survey, but only 160 respondents (69%) met inclusion criteria of
      working in primary care and spending more than 50% of their time with patients.
      Almost two-thirds of participants were men, 80% were white, and the age range was
      28 to 83 years. Twenty-two percent of participants recommended HIV testing at the
      initial patient visit, and 18% recommended annual HIV testing for all patients.
      Eighty-seven percent obtained a separate consent form for HIV testing, and 19%
      included HIV testing in general consent forms. About two-thirds of participants
      recommended annual HIV testing for homosexual men. Three factors were associated
      with recommending HIV testing at the initial patient visit: (1) recommending an
      annual HIV test for sexually active patients (odds ratio [OR], 12.82; 95%
      confidence interval [CI], 3.97-41.67); (2) having an agree/strongly agree
      attitude toward HIV testing (OR, 5.59; 95% CI, 1.63-19.23); and (3) obtaining a
      general consent form that included permission for HIV testing (OR, 3.25; 95% CI,
      1.07-9.90). CONCLUSION: osteopathic physicians who practice primary care medicine
      can play a crucial role in reducing the number of individuals with undiagnosed
      HIV infection. More concerted efforts are needed to help osteopathic physicians
      incorporate HIV testing as part of routine care for all patients.

PMID- 21178153
TI  - Updates in small bowel imaging and endoscopy.
AB  - The field of gastroenterology has had an abundance of technological advances in
      recent years, especially in the field of endoscopy. These advances are helpful to
      clinicians approaching gastrointestinal blood loss, especially in the small
      bowel. The authors report a case of a man who presented to the emergency
      department with obscure gastrointestinal blood loss. Results of an
      esophagogastroduodenoscopy and a colonoscopy suggested the source of the blood
      loss was within the small bowel. On an outpatient basis, the patient underwent
      video capsule endoscopy, which revealed scattered distal duodenal arteriovenous
      malformations. He then underwent oral double balloon endoscopy with ablation of
      the arteriovenous malformations, with no further bleeding or drop in hemoglobin.
      The authors review advances in small bowel imaging and endoscopy, including video
      capsule endoscopy, double balloon endoscopy, and computed tomography
      enterography. A comprehensive data review was conducted by searching the National
      Library of Medicine's PubMed database to identify recent published literature in
      the fields of radiology and gastroenterology. The authors apply these findings to
      the workup and diagnosis of obscure gastrointestinal blood loss.

PMID- 21178154
TI  - Toward an osteopathic psychiatry: the biocognitive model of mind.
AB  - Osteopathic medicine represents a valid tradition in Western medicine, but there
      are concerns about whether it is a viable tradition: will it end up a "poorer
      cousin" of the allopathic tradition or will it eventually simply be absorbed by
      the dominant model? This is particularly the case in psychiatry, where
      osteopathic medicine has never established a firm presence. Currently, the
      dominant ethos in psychiatry is reductive biologism, which tries to eliminate the
      notion of mind as a causative factor in behavior. The author's case is that this
      has failed to give rise to a human-centered psychiatry. His own model of mental
      disorder, the biocognitive model, is based on a molecular resolution of the mind
      body problem (ie, the ancient question of how the immaterial mind and the
      material body interact). It is manifestly dualist (ie, it accords causative
      primacy to mind). This is firmly in the osteopathic medical tradition and is
      offered as a means of developing a distinctive model of psychiatry and hence a
      holistic general medicine.

PMID- 21178155
TI  - A 65-year-old man with shortness of breath, pleuritic chest pain, and recurrent
      pneumonia.
AB  - Recurrent pulmonary infections are common among patients with chronic obstructive
      pulmonary disease. Imaging of the thorax beyond a routine chest radiograph, such
      as computed tomography imaging, should be considered for these patients.
      Fiberoptic bronchoscopy should also be considered for these patients, especially
      in cases in which respiratory cultures do not provide guidance for antibiotic
      therapy. The patient in the present case report experienced recurrent pneumonias
      despite adequate treatment with intravenous and oral antibiotics. He underwent
      computed tomography imaging of the thorax, which demonstrated a suspicious lesion
      in the left mainstem bronchus. This finding prompted a fiberoptic bronchoscopy,
      which revealed an endobronchial tumor. Given the patient's history of cigarette
      smoking, it was surprising to find that he had a benign endobronchial neurogenic
      tumor, which was removed in subsequent rigid bronchoscopy.

PMID- 21178156
TI  - Combat-related posttraumatic headache: diagnosis, mechanisms of injury, and
      challenges to treatment.

PMID- 21178157
TI  - Brief report of a clinical trial on the duration of middle ear effusion in young
      children using a standardized osteopathic manipulative medicine protocol.

PMID- 21178158
TI  - Is something wrong with osteopathic graduate medical education?

PMID- 21178159
TI  - Osteopathic Medicine's Holistic Approach Is More Important Than Ever.

PMID- 21178160
TI  - Osteopathic medical terminology--redux.

PMID- 21178161
TI  - 'Osteopathic physician' defines our identity.

PMID- 21178162
TI  - It Means Just What I Choose It to Mean--Neither More nor Less.

PMID- 21178163
TI  - Cyanide degradation by Pseudomonas pseudoalcaligenes CECT5344 involves a
      malate:quinone oxidoreductase and an associated cyanide-insensitive electron
      transfer chain.
AB  - The alkaliphilic bacterium Pseudomonas pseudoalcaligenes CECT5344 is able to grow
      with cyanide as the sole nitrogen source. Membrane fractions from cells grown
      under cyanotrophic conditions catalysed the production of oxaloacetate from L
      malate. Several enzymic activities of the tricarboxylic acid and glyoxylate
      cycles in association with the cyanide-insensitive respiratory pathway seem to be
      responsible for the oxaloacetate formation in vivo. Thus, in cyanide-grown cells,
      citrate synthase and isocitrate lyase activities were significantly higher than
      those observed with other nitrogen sources. Malate dehydrogenase activity was
      undetectable, but a malate:quinone oxidoreductase activity coupled to the cyanide
      insensitive alternative oxidase was found in membrane fractions from cyanide
      grown cells. Therefore, oxaloacetate production was linked to the cyanide
      insensitive respiration in P. pseudoalcaligenes CECT5344. Cyanide and
      oxaloacetate reacted chemically inside the cells to produce a cyanohydrin (2
      hydroxynitrile), which was further converted to ammonium. In addition to cyanide,
      strain CECT5344 was able to grow with several cyano derivatives, such as 2- and 3
      hydroxynitriles. The specific system required for uptake and metabolization of
      cyanohydrins was induced by cyanide and by 2-hydroxynitriles, such as the
      cyanohydrins of oxaloacetate and 2-oxoglutarate.

PMID- 21178164
TI  - Multilocus sequence typing reveals a novel subspeciation of Lactobacillus
      delbrueckii.
AB  - Currently, the species Lactobacillus delbrueckii is divided into four subspecies,
      L. delbrueckii subsp. delbrueckii, L. delbrueckii subsp. bulgaricus, L.
      delbrueckii subsp. indicus and L. delbrueckii subsp. lactis. These
      classifications were based mainly on phenotypic identification methods and few
      studies have used genotypic identification methods. As a result, these subspecies
      have not yet been reliably delineated. In this study, the four subspecies of L.
      delbrueckii were discriminated by phenotype and by genotypic identification
      [amplified-fragment length polymorphism (AFLP) and multilocus sequence typing
      (MLST)] methods. The MLST method developed here was based on the analysis of
      seven housekeeping genes (fusA, gyrB, hsp60, ileS, pyrG, recA and recG). The MLST
      method had good discriminatory ability: the 41 strains of L. delbrueckii examined
      were divided into 34 sequence types, with 29 sequence types represented by only a
      single strain. The sequence types were divided into eight groups. These groups
      could be discriminated as representing different subspecies. The results of the
      AFLP and MLST analyses were consistent. The type strain of L. delbrueckii subsp.
      delbrueckii, YIT 0080(T), was clearly discriminated from the other strains
      currently classified as members of this subspecies, which were located close to
      strains of L. delbrueckii subsp. lactis. The MLST scheme developed in this study
      should be a useful tool for the identification of strains of L. delbrueckii to
      the subspecies level.

PMID- 21178165
TI  - The soxRS response of Escherichia coli can be induced in the absence of oxidative
      stress and oxygen by modulation of NADPH content.
AB  - The soxRS regulon protects Escherichia coli cells against superoxide and nitric
      oxide. Oxidation of the SoxR sensor, a [2Fe-2S]-containing transcriptional
      regulator, triggers the response, but the nature of the cellular signal sensed by
      SoxR is still a matter of debate. In vivo, the sensor is maintained in a reduced,
      inactive state by the activities of SoxR reductases, which employ NADPH as an
      electron donor. The hypothesis that NADPH levels affect deployment of the soxRS
      response was tested by transforming E. coli cells with genes encoding enzymes and
      proteins that lead to either build-up or depletion of the cellular NADPH pool.
      Introduction of NADP(+)-reducing enzymes, such as wheat non-phosphorylating
      glyceraldehyde-3-phosphate dehydrogenase or E. coli malic enzyme, led to NADPH
      accumulation, inhibition of the soxRS regulon and enhanced sensitivity to the
      superoxide propagator methyl viologen (MV). Conversely, expression of pea
      ferredoxin (Fd), a redox shuttle that can oxidize NADPH via ferredoxin-NADP(H)
      reductase, resulted in execution of the soxRS response in the absence of
      oxidative stress, and in higher tolerance to MV. Processes that caused NADPH
      decline, including oxidative stress and Fd activity, correlated with an increase
      in total (NADP(+)+NADPH) stocks. SoxS expression can be induced by Fd expression
      or by MV in anaerobiosis, under conditions in which NADPH is oxidized but no
      superoxide can be formed. The results indicate that activation of the soxRS
      regulon in E. coli cells exposed to superoxide-propagating compounds can be
      triggered by depletion of the NADPH stock rather than accumulation of superoxide
      itself. They also suggest that bacteria need to finely regulate homeostasis of
      the NADP(H) pool to enable proper deployment of this defensive response.

PMID- 21178166
TI  - Recombinant lactobacilli expressing linoleic acid isomerase can modulate the
      fatty acid composition of host adipose tissue in mice.
AB  - We have previously demonstrated that oral administration of a metabolically
      active Bifidobacterium breve strain, with ability to form cis-9, trans-11
      conjugated linoleic acid (CLA), resulted in modulation of the fatty acid
      composition of the host, including significantly elevated concentrations of c9,
      t11 CLA and omega-3 (n-3) fatty acids in liver and adipose tissue. In this study,
      we investigated whether a recombinant lactobacillus expressing linoleic acid
      isomerase (responsible for production of t10, c12 CLA) from Propionibacterium
      acnes (PAI) could influence the fatty acid composition of different tissues in a
      mouse model. Linoleic-acid-supplemented diets (2 %, w/w) were fed in combination
      with either a recombinant t10, c12 CLA-producing Lactobacillus paracasei NFBC 338
      (Lb338), or an isogenic (vector-containing) control strain, to BALB/c mice for 8
      weeks. A third group of mice received linoleic acid alone (2 %, w/w). Tissue
      fatty acid composition was assessed by GLC at the end of the trial. Ingestion of
      the strain expressing linoleic acid isomerase was associated with a 4-fold
      increase (P<0.001) in t10, c12 CLA in adipose tissues of the mice when compared
      with mice that received the isogenic non-CLA-producing strain. The livers of the
      mice that received the recombinant CLA-producing Lb338 also contained a 2.5-fold
      (albeit not significantly) higher concentration of t10, c12 CLA, compared to the
      control group. These data demonstrate that a single gene (encoding linoleic acid
      isomerase) expressed in an intestinal microbe can influence the fatty acid
      composition of host fat.

PMID- 21178167
TI  - Effects of high-pressure carbon dioxide on proteins and DNA in Escherichia coli.
AB  - Protein changes in Escherichia coli, when subjected to high-pressure carbon
      dioxide (HPCD) at 10 MPa and 3  degrees C for 5-75 min, were assessed using the
      Bradford method, 2D electrophoresis (2-DE) and liquid chromatography-electrospray
      ionization-MS-MS (LC-ESI-MS-MS). The changes in DNA in E. coli under the same
      conditions were also investigated by using flow cytometry with propidium iodide
      and acridine orange, agarose gel electrophoresis (AGE) and the comet assay. The
      results showed that HPCD induced leakage loss of the proteins and DNA of E. coli
      as a function of treatment time. With regard to the protein changes, 182 proteins
      in the 2-DE profile were not found in the HPCD-treated E. coli. Among 20 selected
      protein spots exhibiting significant changes in intensity, 18 protein spots were
      identified as 15 known proteins and two as hypothetical proteins. These proteins
      were involved in cell composition, energy metabolism pathways, nucleic acid
      metabolism, global stress regulation and general metabolism. The DNA denaturation
      of E. coli induced by HPCD was demonstrated in this study for the first time to
      our knowledge, and the denaturation was enhanced by increasing treatment time.
      However, HPCD did not cause DNA degradation, as suggested by both AGE analysis
      and the comet assay.

PMID- 21178168
TI  - Enhanced recovery of Salmonella Typhimurium DT104 from exposure to stress at low
      temperature.
AB  - Salmonella enterica serovar Typhimurium (S. Typhimurium) remains an important
      cause of food-borne infection in the developed world. In order to establish
      infection within a host, Salmonella must survive and recover from a range of
      environmental stresses. S. Typhimurium strain SL1344 is among the most
      extensively studied pathogenic Salmonella strains, while S. Typhimurium phage
      type DT104 is an important type that has been associated with pandemic spread and
      a high number of food-borne disease outbreaks over the last two decades. In this
      study, we have compared the abilities of these two S. Typhimurium types to
      recover from stress exposures commonly encountered in food production, including
      685 mM NaCl, pH 3.8, low temperature (6  degrees C) and combinations thereof.
      Following removal from prolonged (8 days) stress, DT104 cultures that had been
      exposed to low temperature, with or without additional stress, resumed
      exponential growth more rapidly than SL1344 cultures exposed to the same
      conditions. SL1344 showed higher levels of filamentation than DT104 in response
      to NaCl exposure at low temperature. Further, SL1344 incurred higher levels of
      membrane damage in response to elevated NaCl and pH 3.8 at both temperatures
      compared with DT104. However, both strains recovered normal cell division and
      membrane integrity within 6 h when all stresses were removed. Expression of the
      Salmonella pathogenicity island 1 gene prgH, the first gene in the prg/org
      operon, was monitored using a chromosomal reporter in which gfp(+) expression was
      driven by the prgH promoter. Recovery of prgH expression was comparable for
      SL1344 and DT104 exposed to stress at 22  degrees C. However, DT104 cultures
      exposed to pH 3.8 or combined NaCl and low-pH stress at low temperature resumed
      prgH expression more rapidly than SL1344. Both strains recovered maximal levels
      of prgH expression after 6 h recovery from all stresses and, interestingly,
      maximal levels of prgH expression were significantly higher in SL1344, consistent
      with prgH expression in late-exponential, non-stressed SL1344 and DT104 cultures.
      Together, these data show that S. Typhimurium is capable of rapid recovery from
      environmental and food-related stresses, and give insight into the enhanced
      ability of DT104 compared with SL1344 to adapt to such stresses, which may
      contribute to the success of this globally disseminated pathogenic phage type.

PMID- 21178170
TI  - Phenotypic characterization by high-resolution three-dimensional magnetic
      resonance imaging evidences differential effects of embryo genotype on
      intrauterine growth retardation in NOS3-deficient mice.
AB  - The Nos3-knockout mouse, deficient for endothelial constitutive nitric oxide
      synthase (NOS3), is affected by a reduction in the number and weight of the
      embryos and constitutes a good model for some features of preeclampsia and
      intrauterine growth retardation (IUGR). Deficiencies in conceptus growth and
      survival may result from factors inherent in the embryo itself or from
      deficiencies in uterine function. In the current study, we aimed to determine the
      effects of embryonic genotype independently of maternal genotype, which can
      affect uterine environment. Therefore, by using magnetic resonance imaging (MRI),
      we characterized the phenotypes of NOS3-defective (Nos3(-/-); n = 6), normal wild
      type (Nos3(+/+); n = 5), and heterozygous (Nos3(+/-); n = 16) mouse fetuses. All
      of them were littermates obtained by breeding heterozygous mice (Nos3(+/-));
      therefore, the maternal genotype was the same for all the fetuses. At Day 13.5
      (i.e., Theiler stage TS 21-22), females were anesthetized and scanned with three
      dimensional MRI. Analysis of the different measurements of the embryos and the
      gestational annexes showed no significant differences between Nos3(+/+) and
      Nos3(+/-); however, there was a trend toward larger sizes in Nos3(+/+), and
      values in Nos3(-/-) were significantly smaller than in Nos3(+/+) and Nos3(+/-).
      The reduction in the crown-rump length of Nos3(-/-) reached 12% when compared to
      Nos3(+/+) (P < 0.05); the effect was higher for head measurements (16% for
      occipito-snout length and biparietal diameter, P < 0.05 for both) and trunk
      diameter (17%, P < 0.05). Overall, the maximum area of fetuses in longitudinal
      planes decreased 27% (P < 0.05) when comparing Nos3(-/-) to wild-type Nos3(+/+).
      Finally, Nos3(-/-) showed a reduction of 29% in the maximum thickness of the
      placenta, which may be related to the appearance of IUGR due to compromised
      nutritional delivery to the fetus.

PMID- 21178169
TI  - Cytochrome c4 is required for siderophore expression by Legionella pneumophila,
      whereas cytochromes c1 and c5 promote intracellular infection.
AB  - A panel of cytochrome c maturation (ccm) mutants of Legionella pneumophila
      displayed a loss of siderophore (legiobactin) expression, as measured by both the
      chrome azurol S assay and a Legionella-specific bioassay. These data, coupled
      with the finding that ccm transcripts are expressed by wild-type bacteria grown
      in deferrated medium, indicate that the Ccm system promotes siderophore
      expression by L. pneumophila. To determine the basis of this newfound role for
      Ccm, we constructed and tested a set of mutants specifically lacking individual c
      type cytochromes. Whereas ubiquinol-cytochrome c reductase (petC) mutants
      specifically lacking cytochrome c(1) and cycB mutants lacking cytochrome c(5) had
      normal siderophore expression, cyc4 mutants defective for cytochrome c(4)
      completely lacked legiobactin. These data, along with the expression pattern of
      cyc4 mRNA, indicate that cytochrome c(4) in particular promotes siderophore
      expression. In intracellular infection assays, petC mutants and cycB mutants, but
      not cyc4 mutants, had a reduced ability to infect both amoebae and macrophage
      hosts. Like ccm mutants, the cycB mutants were completely unable to grow in
      amoebae, highlighting a major role for cytochrome c(5) in intracellular
      infection. To our knowledge, these data represent both the first direct
      documentation of the importance of a c-type cytochrome in expression of a
      biologically active siderophore and the first insight into the relative
      importance of c-type cytochromes in intracellular infection events.

PMID- 21178171
TI  - Differential changes in responses of hypothalamic and brainstem neuronal
      populations to prolactin during lactation in the mouse.
AB  - During lactation, there are numerous functional adaptations in the maternal
      brain. There is evidence that the high levels of circulating prolactin present
      during lactation might contribute to these adaptive changes. The present study
      aimed to investigate levels of functional prolactin-mediated signal transduction
      in the brain of lactating mice, using prolactin-induced phosphorylation of signal
      transducer and activator of transcription 5 (pSTAT5) as a marker, and compare
      these to the effect of exogenous prolactin during diestrus. On Day 7 of
      lactation, widespread induction of pSTAT5 was observed in numerous regions of the
      mouse forebrain and brainstem. In the medial preoptic nucleus, bed nuclei stria
      terminalis, paraventricular nucleus, and medial amygdala of the forebrain, and in
      the rostral periaqueductal gray, parabrachial nucleus, dorsal raphe, and the
      raphe obscurus nucleus of the brainstem, pSTAT5 expression was markedly increased
      during lactation compared with the response to exogenous prolactin during
      diestrus. In the anteroventral periventricular nucleus, arcuate nucleus,
      ventromedial nucleus, and dorsomedial nucleus, responses in lactation were
      comparable to diestrus. Conversely, in the area postrema of the brainstem, there
      was a reduction in response to prolactin, with a loss of pSTAT5 expression,
      during lactation. These differential responses following either acute or chronic
      elevations in prolactin were not accompanied by any changes in levels of
      prolactin receptor mRNA, when measured by in situ hybridization. These data are
      consistent with the hypothesis that prolactin might mediate widespread adaptive
      responses in the maternal brain.

PMID- 21178172
TI  - Species-specific telomere length differences between blastocyst cell compartments
      and ectopic telomere extension in early bovine embryos by human telomerase
      reverse transcriptase.
AB  - The enzyme telomerase is active in germ cells and is critically involved in
      maintenance of telomere length in successive generations. In preimplantation
      mammalian embryos, telomerase activity is present from the morula stage onward
      and is associated with an increase in telomere length in blastocysts. Herein, we
      show that telomere length regulation in murine and bovine blastocysts differed
      between trophectodermal and inner cell mass cells in a species-specific manner.
      Ectopic expression of human telomerase reverse transcriptase (TERT) in bovine
      embryos increased telomerase activity and in turn increased telomere length.
      Transient expression of human TERT could be targeted to the 4-cell to morula
      stages and to the morula to blastocyst stages using unmodified and cytosine
      methylated expression plasmids, respectively. Introduction of human TERT
      constructs in bovine embryos resulted in functional telomerase expression and
      effective telomere elongation, allowing us to study the effects on embryonic
      development. Ultimately, these studies may lead to a large-animal model for
      telomere regulation and aging.

PMID- 21178173
TI  - Oocyte-expressed interleukin 7 suppresses granulosa cell apoptosis and promotes
      oocyte maturation in rats.
AB  - Development of ovarian follicles is regulated by pituitary-derived gonadotropins
      together with local ovarian paracrine factors. Based on DNA microarray data, we
      performed RT-PCR and immunostaining to demonstrate the expression of interleukin
      7 transcripts in oocytes of preantral, antral, and preovulatory follicles in
      rats. We also found the expression of interleukin 7 receptor and the coreceptor
      interleukin 2 receptor gamma in granulosa cells, cumulus cells, and preovulatory
      oocytes. In cultured rat granulosa cells obtained from early antral and
      preovulatory follicles, treatment with interleukin 7 stimulated the
      phosphorylation of AKT, glycogen synthase kinase (GSK3B), and STAT5 proteins in a
      time- and dose-dependent manner. Furthermore, measurement of mitochondrial
      reductase activity indicated that treatment with interleukin 7, similar to
      gonadotropins, increased the number of viable granulosa cells during a 24-h
      culture period. Furthermore, monitoring of the activities of apoptotic enzymes
      (caspase 3/7) indicated that treatment with interleukin 7 suppressed apoptosis of
      cultured granulosa cells from both antral and preovulatory follicles following
      serum withdrawal. The apoptosis-suppressing actions of interleukin 7 were blocked
      by an inhibitor of the phosphoinositol-3-kinase (PIK3)/AKT pathway. Furthermore,
      treatment of cultured preovulatory follicles with interleukin 7, like treatment
      with human chorionic gonadotropin, induced germinal vesicle breakdown of oocytes.
      The stimulatory effect of interleukin 7 was also blocked by inhibitors of the
      PIK3/AKT pathway. The present findings suggest that oocyte-derived interleukin 7
      could act on neighboring granulosa cells as a survival factor and promote the
      nuclear maturation of preovulatory oocytes through activation of the PIK3/AKT
      pathway.

PMID- 21178174
TI  - Are there benefits from having two genetic fathers?
AB  - In this issue of Biology of Reproduction, Deng and colleagues present a method by
      which offspring originating from two male mouse genomes can efficiently be
      produced.

PMID- 21178176
TI  - Adverse events associated with the use of complementary and alternative medicine
      in children.
AB  - OBJECTIVE: To determine the types of adverse events associated with the use of
      complementary and alternative medicine (CAM) that come to the attention of
      Australian paediatricians. DESIGN: Monthly active surveillance study of CAM
      associated adverse events as reported to the Australian Paediatric Surveillance
      Unit between January 2001 and December 2003. RESULTS: There were 39 reports of
      adverse events associated with CAM use, including four reported deaths. Reports
      highlighted several areas of concern, including the risks associated with failure
      to use conventional medicine, the risks related to medication changes made by CAM
      practitioners and the significant dangers of dietary restriction. The reported
      deaths were associated with a failure to use conventional medicine in favour of a
      CAM therapy. CONCLUSION: CAM use has the potential to cause significant morbidity
      and fatal adverse outcomes. The diversity of CAM therapies and their associated
      adverse events demonstrate the difficulty addressing this area and the importance
      of establishing mechanisms by which adverse effects may be reported or monitored.

PMID- 21178175
TI  - The impact of deprivation on youth violence: a comparison of cities and their
      feeder towns.
AB  - BACKGROUND AND AIMS: 66,000 children and adolescents are treated at emergency
      departments (EDs) in England and Wales each year for assault injury. The aim of
      this study was to compare adolescent assault injury rates in cities and towns and
      determine how assault injury varies with deprivation and gender. METHODS: The
      study was set in three cities in Wales, UK, and their surrounding towns. Subjects
      were 11-17 year olds treated for assault injury at one of seven EDs from 1
      October 2005 to 30 September 2006. Area of residence (electoral divisions, EDivs)
      was identified from patient postcode. EDivs were aggregated into deprivation
      fifths for males and females and cities and towns. Assault injury rates, rate
      ratios and 95% CIs were calculated. RESULTS: 1472 children and adolescents of 11
      17 years old were treated for assault injury. Male city assault injury rates were
      14.2/1000 11-17 year olds; and 13.1 in towns. Female city assault injury rates
      were 6.0; and 5.6 in towns. In the most deprived city areas males had assault
      injury rates 2.6 times (95% CI 1.85 to 3.59) that of the most affluent, compared
      with 2.0 times in towns (95% CI 1.39 to 2.86). For females, the most deprived
      city areas had assault injury rates 5.3 times that of the most affluent (95% CI
      2.93 to 9.41), compared with 2.8 times in towns (95% CI 1.47 to 5.28).
      CONCLUSIONS: Injury in youth violence increased with increasing deprivation in
      cities and their feeder towns. This was true for boys and girls, though rates for
      boys were consistently higher. This link between assault injury and deprivation
      was stronger for girls in cities than in feeder towns. Strategies to prevent
      youth violence need to include improved safeguarding arrangements for girls
      living in the most deprived city areas.

PMID- 21178177
TI  - Effects of polymorphisms in the calpastatin and MU-calpain genes on meat
      tenderness in 3 French beef breeds.
AB  - The objectives of the study were to evaluate allelic frequencies and to test the
      association of polymorphisms in the calpastatin (CAST) and u-calpain (CAPN1)
      genes with meat tenderness in 3 French beef breeds. A total of 1,114 Charolais,
      1,254 Limousin, and 981 Blonde d'Aquitaine purebred young bulls were genotyped
      for 3 SNP in the CAST gene and 4 SNP in the CAPN1 gene. Two of these markers, 1
      in each gene, can be found in Australian or American commercial genetic tests.
      Others have previously been reported in American studies or are newly evidenced
      SNP. The quantitative traits studied were Warner-Bratzler shear force and a
      tenderness score evaluated by trained sensory panels. All the SNP were
      informative in the 3 breeds. Associations of individual markers or haplotypes
      with traits were analyzed. The results differed in the 3 breeds. The G allele of
      a CAST marker (position 97574679 on Btau4.0) was found to exert a significant
      effect on the shear force (+0.18 phenotypic SD; RSD) and tenderness score (-0.22
      RSD) in the Blonde d'Aquitaine breed. In the same breed, this marker was
      associated with another CAST SNP (position 97576054 on Btau4.0) such that the GA
      haplotype appeared to be associated with tougher meat. Two CAPN1 markers
      (positions 45221250 and 45241089 on Btau4.0) had a significant effect on both
      traits in the Charolais breed (from |0.11| to |0.25| RSD). In the same breed,
      these markers were associated with another CAPN1 SNP (position 45219395 on
      Btau4.0) such that the ACA and AGG haplotypes appeared to be associated with a
      tender meat and a tougher meat, respectively. Consequently, the present results
      indicate that the effects of the markers studied are breed-specific and cannot be
      extended to all Bos taurus breeds. Further studies are also required to identify
      other more appropriate markers for French beef breeds.

PMID- 21178178
TI  - Genetic parameters for cattle price and body weight from routinely collected data
      at livestock auctions and commercial farms.
AB  - Beef outputs from dairy farms make an important contribution to overall
      profitability in Irish dairy herds and are the sole source of revenue in many
      beef herds. The aim of this study was to estimate genetic parameters for animal
      BW and price across different stages of maturity. Data originated from 2 main
      sources: price and BW from livestock auctions and BW from on-farm weighings
      between 2000 and 2008. The data were divided into 4 distinct maturity categories:
      calves (n = 24,513), weanlings (n = 27,877), postweanlings (n = 23,279), and cows
      (n = 4,894). A univariate animal model used to estimate variance components was
      progressively built up to include a maternal genetic effect and a permanent
      environmental maternal effect. Bivariate analyses were used to estimate genetic
      covariances between BW and price per animal within and across maturity category.
      Direct heritability estimates for price per animal were 0.34 +/- 0.03, 0.31 +/-
      0.05, 0.19 +/- 0.04, and 0.10 +/- 0.04 for calves, weanling, postweanlings, and
      cows, respectively. Direct heritability estimates for BW were 0.26 +/- 0.03 for
      weanlings, 0.25 +/- 0.04 for postweanlings, and 0.24 +/- 0.06 for cows; no BW
      data were available on calves. Significant maternal genetic and maternal
      permanent environmental effects were observed for weanling BW only. The genetic
      correlation between price per animal and BW within each maturity group varied
      from 0.55 +/- 0.06 (postweanling price and BW) to 0.91 +/- 0.04 (cow price and
      BW). The availability of routinely collected data, along with the existence of
      ample genetic variation for animal BW and price per animal, facilitates their
      inclusion in Irish dairy and beef breeding objectives to better reflect the
      profitability of both enterprises.

PMID- 21178179
TI  - Maternal selenium supplementation and timing of nutrient restriction in pregnant
      sheep: Impacts on nutrient availability to the fetus.
AB  - To determine the effects of maternal Se intake and plane of nutrition during mid
      or late gestation or both on AA concentrations and metabolite concentrations in
      the dam and fetus, pregnant ewe lambs (n = 64) were assigned to 1 of 8 treatments
      arranged in a 2 * 2 * 2 factorial array: Se level [initiated at breeding;
      adequate (ASe; 3.05 MUg/kg of BW) or high (HSe; 70.4 MUg/kg of BW)] and
      nutritional level [100% (control; CON) or 60% (restricted; RES) of NRC
      recommendations] fed at different times of gestation [d 50 to 90 (mid) or d 91 to
      132 (late)]. A blood sample was obtained from each ewe and fetus on d 132 of
      gestation and used to measure circulating concentrations of glucose, NEFA, blood
      urea N, and AA. The late RES ewes and their fetuses had less (P <= 0.03)
      circulating glucose compared with late CON ewes and fetuses at d 132; however, no
      effect (P >= 0.14) of diet on the fetal:maternal glucose concentration ratio was
      observed. Late RES ewes had a smaller (P = 0.01) fetal:maternal NEFA ratio
      compared with late CON ewes. Ewes fed ASe had a greater (P = 0.01) fetal:maternal
      blood urea N ratio compared with HSe ewes. Fetal:maternal ratios of total
      circulating AA, total essential AA, and total nonessential AA were each affected
      (P <= 0.03) by the combination of Se treatment and late gestation nutritional
      level.

PMID- 21178180
TI  - The threonine requirement of sows increases in late gestation.
AB  - Current AA recommendations for sows are to provide a fixed amount of AA intake
      throughout gestation based on the assumption that there is a constant demand for
      AA; however, the demand for nutrients changes from maternal lean tissue in early
      gestation to fetal and mammary growth in late gestation. The objective of this
      study was to determine the Thr requirement in early (d 35 to 53 and 25 to 55 for
      Exp. 1 and 2, respectively) and late (d 92 to 110 and 81 to 111 for Exp. 1 and 2,
      respectively) gestation using the indicator AA oxidation (IAAO) method with l-[1
      (13)C]Phe as the tracer AA. A total of 14 multiparous sows were used: 6 in Exp. 1
      and 8 in Exp. 2. Each sow received each of 6 diets in random order in both early
      and late gestation. A basal diet was formulated to contain Thr at 60% of the 1998
      NRC recommendation in Exp. 1 and 20 and 60% of the 1998 NRC in Exp. 2 for early
      and late gestation, respectively. Crystalline l-Thr was added to create
      additional diets with approximately 10% incremental increases in Thr. Sows were
      placed in respiration chambers, and expired air and blood were collected every 30
      min for 5.5 h. Tracer Phe [mg/(kg of BW.h)] was given orally over the last 4 h
      divided into eight 0.5-h meals. Expired air and plasma were measured for
      (13)CO(2) enrichment and free Thr concentration, respectively. Background
      (13)CO(2) was subtracted from plateau (13)CO(2) enrichment. Data were analyzed
      using a 2-phase nonlinear Mixed model. The overall litter size and litter weight
      were 13.5 +/- 3.1 and 20.5 +/- 3.9 kg, respectively. Based on IAAO, the Thr
      requirement in early gestation was 6.1 g/d (R(2) = 0.59, Exp. 1) and 5.0 g/d
      (R(2) = 0.71, Exp. 2). In late gestation, the Thr requirement based on IAAO was
      13.6 g/d (R(2) = 0.60, Exp. 1) and 12.3 g/d (R(2) = 0.58, Exp. 2). Based on
      plasma Thr, the Thr requirement in early gestation was 7.0 g/d (R(2) = 0.90, Exp.
      1) and 3.9 g/d (R(2) = 0.90, Exp. 2). In late gestation, the Thr requirement
      based on plasma Thr was 10.5 g/d (R(2) = 0.67, Exp. 2). There was a linear
      response to increasing Thr intake in late gestation in Exp. 1. Feeding a single
      amount of AA throughout gestation results in overfeeding AA in early gestation
      and underfeeding AA in late gestation. The 2-fold increase in Thr requirement in
      the last third of gestation suggests that phase feeding sows in gestation will
      more closely meet the demands for nutrients and that the requirement for
      essential AA in gestating sows should be re-evaluated in early and late gestation
      separately.

PMID- 21178181
TI  - Effect of feeding fat or intrajugular infusion of glucagon-like peptide-1 and
      cholecystokinin on dry matter intake, digestibility, and digesta rate of passage
      in growing wethers.
AB  - A cause and effect relationship between glucagon-like peptide 1 (7, 36) amide
      (GLP-1) and cholecystokinin (CCK) and DMI regulation has not been established in
      ruminants. Three randomized complete block experiments were conducted to
      determine the effect of feeding fat or infusing GLP-1 or CCK intravenously on
      DMI, nutrient digestibility, and Cr rate of passage (using Cr(2)O(3) as a marker)
      in wethers. A total of 18 Targhee * Hampshire wethers (36.5 +/- 2.5 kg of BW)
      were used, and each experiment consisted of four 21-d periods (14 d for
      adaptation and 7 d for infusion and sampling). Wethers allotted to the control
      treatments served as the controls for all 3 experiments; experiments were
      performed simultaneously. The basal diet was 60% concentrate and 40% forage. In
      Exp. 1, treatments were the control (0% added fat) and addition of 4 or 6% Ca
      salts of palm oil fatty acids (DM basis). Treatments in Exp. 2 and 3 were the
      control and 3 jugular vein infusion dosages of GLP-1 (0.052, 0.103, or 0.155
      ug*kg of BW(-1)*d(-1)) or CCK (0.069, 0.138, or 0.207 ug*kg of BW(-1)*d(-1)),
      respectively. Increases in plasma GLP-1 and CCK concentrations during hormone
      infusions were comparable with increases observed when increasing amounts of fat
      were fed. Feeding fat and infusion of GLP-1 tended (linear, P = 0.12; quadratic,
      P = 0.13) to decrease DMI. Infusion of CCK did not affect (P > 0.21) DMI.
      Retention time of Cr in the total gastrointestinal tract decreased (linear, P <
      0.01) when fat was fed, but was not affected by GLP-1 or CCK infusion. In
      conclusion, jugular vein infusion produced similar plasma CCK and GLP-1
      concentrations as observed when fat was fed. The effects of feeding fat on DMI
      may be partially regulated by plasma concentration of GLP-1, but are not likely
      due solely to changes in a single hormone concentration.

PMID- 21178182
TI  - Effects of sequential implanting and ractopamine hydrochloride supplementation on
      carcass characteristics and longissimus muscle tenderness of calf-fed steers and
      heifers.
AB  - A 4 * 2 factorial arrangement of treatments (4 growth-enhancement treatments * 2
      sex classes) was used to quantify effects of initial implanting (I-implant, d 0),
      terminal implanting (T-implant, d 63), and feeding ractopamine hydrochloride
      [RAC, 200 mg/(animal/d)] for the last 28 d on feed on carcass characteristics and
      LM shear force (WBSF) of calf-fed steers (n = 159) and heifers (n = 132). Growth
      enhancement treatments included the following: TRT1, T-implant only; TRT2, I
      implant and RAC; TRT3, I-implant and T-implant; TRT4, I-implant, T-implant, and
      RAC. Growth responses (BW and ADG) were measured in 3 segments of the finishing
      period: 1) d 0 to 63, 2) d 63 to 28 d before slaughter, and 3) final 28 d. Cattle
      were slaughtered after 152, 166, or 180 d of finishing; carcass data were
      collected after a 48-h chill; and LM WBSF was measured at 3, 7, 14, 21, and 28 d
      postmortem. A priori contrasts were constructed to test effects associated with
      use vs. exclusion of growth enhancement in each segment of the finishing period.
      The interaction between sex class and treatment was not significant (P > 0.05)
      for any trait tested, indicating that the 4 treatments elicited similar effects
      in both sexes. Initial implanting improved (P < 0.001) ADG from d 0 to 63 by
      11.5%, terminal implanting improved (P < 0.001) ADG from d 63 to 28 d before
      slaughter by 15%, and supplementing twice-implanted cattle with RAC enhanced ADG
      during the final 28 d of finishing by 12%. Effects of I-implant, T-implant, and
      RAC resulted in LM area increases of 3 cm(2) (P = 0.015), 6 cm(2) (P < 0.001),
      and 3 cm(2) (P = 0.011), respectively, and HCW responses of 11 kg (P = 0.011), 16
      kg (P = 0.001), and 6 kg (P = 0.195), respectively. Initial implanting resulted
      in a 20-point reduction (P = 0.097) in marbling, and T-implant reduced marbling
      by 25 points (P = 0.04), whereas marbling score was unaffected (P = 0.236) by RAC
      supplementation. Cattle that received only 1 implant (TRT1 and TRT2) produced
      carcasses with greater (P = 0.026) mean marbling scores and greater (P = 0.01)
      rates of conformity to beef carcass marketing specifications for HCW, quality
      grade, yield grade, and LM area than did cattle that were implanted twice (TRT3
      and TRT4). Values for LM WBSF were not affected (P > 0.05) by initial or terminal
      implanting; however, RAC supplementation increased (P = 0.007) mean LM WBSF by
      0.23 kg, which translated into a reduction (P = 0.007) in predicted consumer
      acceptance of LM steaks.

PMID- 21178183
TI  - Genotype x environment interactions for fatty acid profiles in Bos indicus and
      Bos taurus finished on pasture or grain.
AB  - A study was conducted to characterize lipid profiles in the M. longissimus
      thoracis of commercial Brazilian beef and to assess how those profiles are
      influenced by finishing system, genetic group, and their interaction.
      Intramuscular fat (IMF) and fatty acid (FA) profiles were determined in 160 bulls
      of the Bos taurus (n = 75) and Bos indicus (n = 85) genetic groups, finished on
      pasture (n = 46) or with grain supplementation (n = 114) and slaughtered in a
      commercial abattoir. Finishing system had a major impact on the deposition of
      IMF, as well as on the concentration of SFA, PUFA, and their ratio, but genetic
      groups showed important differences in the ability to convert SFA into cis-9 MUFA
      and to convert 16:0 into 18:0. When compared with pasture-finished animals, those
      finished with grain had greater content of IMF and SFA (P < 0.01), similar
      amounts of MUFA (P > 0.05), and about one-half the amount of PUFA (P < 0.01).
      Except for MUFA, differences in FA profiles among finishing systems were mostly
      mediated through their effect on IMF, even though the relationship of IMF with
      groups of FA differed among finishing systems. Under grain finishing, B. taurus
      had less SFA and greater MUFA than B. indicus (P < 0.01), but no differences were
      observed in PUFA (P > 0.05). With pasture-finishing, no differences were observed
      among the 2 genetic groups in SFA and MUFA (P > 0.05), but PUFA were decreased in
      B. taurus (P < 0.01). When genetic groups were compared in grain-finishing, B.
      taurus had a decreased ability for elongation and B. indicus had a decreased
      aptitude for desaturation of FA. On the other hand, with pasture-finishing a
      greater deposition of intermediate FA from ruminal biohydrogenation was observed
      in B. indicus than in B. taurus. Overall, FA profiles were affected more by
      finishing system in B. indicus than in B. taurus.

PMID- 21178184
TI  - Social inequalities in quitting smoking: what factors mediate the relationship
      between socioeconomic position and smoking cessation?
AB  - BACKGROUND: Smokers from lower socio-economic groups are less likely to be
      successful in a quit attempt than more affluent smokers, even when they access
      smoking cessation services. METHODS: Data were collected from smoking cessation
      service users from three contrasting areas of Great Britain-Glasgow, North
      Cumbria and Nottingham. Routine monitoring data were supplemented with CO
      validated smoking status at 52-week follow-up and survey data on socio-economic
      circumstances and smoking-related behaviour. Analysis was restricted to the 2397
      clients aged between 25 and 59. RESULTS: At 52-week follow-up, 14.3% of the most
      affluent smokers remained quit compared with only 5.3% of the most disadvantaged.
      After adjustment for demographic factors, the most advantaged clients at the
      English sites and the Glasgow one-to-one programme were significantly more likely
      to have remained abstinent than those who were most disadvantaged [odds ratio:
      2.5, confidence interval (CI): 1.4-4.7 and 7.5 CI: 1.4-40.3, respectively).
      Mechanisms producing the inequalities appeared to include treatment compliance,
      household smokers and referral source. CONCLUSIONS: Rather than quitting smoking,
      disadvantaged smokers quit treatment. More should be done to encourage them to
      persevere through the first few weeks. Other causes of inequalities in quitting
      varied with the service provided.

PMID- 21178185
TI  - Collaborative imperatives, elusive dialogues.

PMID- 21178186
TI  - The right to sutures: social epidemiology, human rights, and social justice.
AB  - The article examines the convergences and contrasts between social epidemiology,
      social medicine, and human rights approaches toward advancing global health and
      health equity. The first section describes the goals and work of the WHO
      Commission on Social Determinants of Health. The second section discusses the
      role of human rights in the Commission's work. The third section evaluates, from
      the perspective of social epidemiology, two rights-based approaches to advancing
      health and health equity as compared to a view that focuses more broadly on
      social justice. The concluding section identifies four areas where social
      epidemiologists, practitioners of social medicine, and health and human rights
      advocates can and must work together in order to make progress on health and
      health equity.

PMID- 21178187
TI  - The social determinants of health, health equity, and human rights.
AB  - This article explores the benefits of a rights-based approach to health according
      greater attention to the social determinants of health, health equity, and the
      power structure. It uses the report issued by the World Health Organization
      Commission on Social Determinants of Health (CSDH), "Closing the gap in a
      generation: Health equity through action on the social determinants of health,"
      as a lens through which to address these issues. After presenting a brief
      overview of the CSDH report, the article compares the document with a rights
      based approach to health on three topics: 1) the social determinants of health
      and the underlying determinants of health; 2) health inequalities and inequities;
      and 3) power, money, and resources. The article argues that the right to health
      requires greater attention to the social determinants of health, health
      inequalities, and power dynamics than these topics have received to date.

PMID- 21178188
TI  - Social conditions, health equity, and human rights.
AB  - The fields of health equity and human rights have different languages,
      perspectives, and tools for action, yet they share several foundational concepts.
      This paper explores connections between human rights and health equity, focusing
      particularly on the implications of current knowledge of how social conditions
      may influence health and health inequalities, the metric by which health equity
      is assessed. The role of social conditions in health is explicitly addressed by
      both 1) the concept that health equity requires equity in social conditions, as
      well as in other modifiable determinants, of health; and 2) the right to a
      standard of living adequate for health. The indivisibility and interdependence of
      all human rights--civil and political as well as economic and social--together
      with the right to education, implicitly but unambiguously support the need to
      address the social (including political) determinants of health, thus
      contributing to the conceptual basis for health equity. The right to the highest
      attainable standard of health strengthens the concept and guides the measurement
      of health equity by implying that the reference group for equity comparisons
      should be one that has optimal conditions for health. The human rights principles
      of non-discrimination and equality also strengthen the conceptual foundation for
      health equity by identifying groups among whom inequalities in health status and
      health determinants (including social conditions) reflect a lack of health
      equity; and by construing discrimination to include not only intentional bias,
      but also actions with unintentionally discriminatory effects. In turn, health
      equity can make substantial contributions to human rights 1) insofar as research
      on health inequalities provides increasing understanding and empiric evidence of
      the importance of social conditions as determinants of health; and, more
      concretely, 2) by indicating how to operationalize the concept of the right to
      health for the purposes of measurement and accountability, which have been
      elusive. Human rights laws and principles and health equity concepts and
      technical approaches can be powerful tools for mutual strengthening, not only by
      contributing toward building awareness and consensus around shared values, but
      also by guiding analysis and strengthening measurement of both human rights and
      health equity.

PMID- 21178189
TI  - Realizing human rights-based approaches for action on the social determinants of
      health.
AB  - Health inequities are clear evidence of violations of the right to health. Yet
      despite this common ground, action on the social determinants of health aiming to
      reduce health inequities is sometimes disconnected from implementation of human
      rights-based approaches. This is explained in part by differing histories,
      disciplines, and epistemologies. The capacity of human rights instruments to
      alter policies on social determinants can seem limited. An absolutist focus on
      individuals and processes can seem at odds with the attention to differences in
      population health outcomes central to the concern for health equity. However,
      developments in rights-based approaches have seen the terrain of human rights
      increasingly address social determinants. Human rights provide a firm legal basis
      for tackling the inequities in power and resources that the Commission on Social
      Determinants of Health identifies as fundamental to achieving health equity.
      Indicators and benchmarks developed for rights-based approaches to health systems
      can be developed further within health sectors and translated to other sectors
      and disciplines. The discourse and evidence base of social determinants can also
      contribute to implementing rights-based approaches, as its resultant policy
      momentum can provide essential levers to realize the right to health. Therefore,
      there is no clear-cut delineation between the human rights and health equity
      movements, and both may constructively work together to realize their goals. Such
      constructive collaboration will not prove straightforward; it will, instead,
      require profound engagement and innovations in both theory and practice. Yet this
      effort represents an important opportunity for those who seek social justice in
      health.

PMID- 21178190
TI  - Human rights assessment in Parc Jean Marie Vincent, Port-au-Prince, Haiti.
AB  - Months after a 7.0 magnitude earthquake hit Port-au-Prince, Haiti, over one
      million remain homeless and living in spontaneous internally displaced person
      (IDP) camps. Billions of dollars from aid organizations and government agencies
      have been pledged toward the relief effort, yet many basic human needs, including
      food, shelter, and sanitation, continue to be unmet. The Sphere Project,
      "Humanitarian Charter and Minimum Standards in Disaster Response," identifies the
      minimum standards to be attained in disaster response. From a human rights
      perspective and utilizing key indicators from the Sphere Project as benchmarks,
      this article reports on an assessment of the living conditions approximately 12
      weeks after the earthquake in Parc Jean Marie Vincent, a spontaneous IDP camp in
      Port-au-Prince. A stratified random sample of households in the camp,
      proportionate to the number of families living in each sector, was selected.
      Interview questions were designed to serve as "key indicators" for the Sphere
      Project minimum standards. A total of 486 interviews were completed, representing
      approximately 5% of households in each of the five sectors of the camp. Our
      assessment identified the relative achievements and shortcomings in the provision
      of relief services in Parc Jean Marie Vincent. At the time of this survey, the
      Sphere Project minimum standards for access to health care and quantity of water
      per person per day were being met. Food, shelter, sanitation, and security were
      below minimum accepted standard and of major concern. The formal assessment
      reported here was completed by September 2010, and is necessarily limited to
      conditions in Haiti before the cholera outbreak in October.

PMID- 21178191
TI  - Correlates of violence in Guinea's Maison Centrale Prison: a statistical approach
      to documenting human rights abuses.
AB  - Les Memes Droits Pour Tous (MDT) is a human rights NGO in Guinea, West Africa
      that focuses on the rights of prisoners in Maison Centrale, the country's largest
      prison located in the capital city of Conakry. In 2007, MDT completed a survey of
      the prison population to assess basic legal and human rights conditions. This
      article uses statistical tools to explore MDT's survey results in greater depth,
      shedding light on human rights violations in Guinea. It contributes to human
      rights literature that argues for greater use of econometric tools in rights
      reporting, and demonstrates how human rights practitioners and academics can work
      together to construct an etiology of violence and torture by state actors, as
      physical violence is perhaps the most extreme violation of the individual's right
      to health.

PMID- 21178192
TI  - Developing human rights-based strategies to improve health among female sex
      workers in Rwanda.
AB  - How governments should address sex work is a topic of current debate in Rwanda
      and other countries. Some constituencies propose harsher punishment of sex
      workers as the cornerstone of an improved policy. We argue that an adequate
      policy response to sex work in the Rwandan context must prioritize public health
      and reflect current knowledge of the social determinants of health. This does not
      imply intensified repression, but a comprehensive agenda of medical and social
      support to improve sex workers' access to health care, reduce their social
      isolation, and expand their economic options. Evidence from social epidemiology
      converges with rights-based arguments in this approach. Recent field interviews
      with current and former sex workers strengthen the case, while highlighting the
      need for further social scientific and epidemiological analysis of sex work in
      Rwanda. Rwanda has implemented some measures that reflect a rights-based
      perspective in addressing sex work. For example, recent policies seek to expand
      access to education for girls and support sex workers in the transition to
      alternative livelihoods. These policies reinforce the model of solidarity-based
      public health action for which Rwanda has been recognized. Whether such measures
      can maintain traction in the face of economic austerity and ideological
      resistance remains to be seen.

PMID- 21178193
TI  - Nurses' impoliteness as an impediment to patients' rights in selected Kenyan
      hospitals.
AB  - The institutionalization of patients' rights is a recent phenomenon in Kenya. In
      2006, Kenya's Ministry of Health initiated policy measures to improve patient
      satisfaction through a charter of patients' rights. The aim was to change the
      longstanding public perception that nurses in public hospitals routinely ignored
      patients' right to respectful treatment. This paper focuses on linguistic
      indicators of violation or promotion of patients' rights in the health care
      context. We examine the extent to which patients' rights to dignity, respect, and
      humaneness are observed or denied, and we argue that impolite utterances impede
      rather than promote the realization of other fundamental human rights. It appears
      that nurses' impoliteness does not merely constitute rudeness, but encodes a
      violation of dignity which, in turn, hampers the chances of enjoyment of broader
      human rights such as the right to autonomy, free expression, self-determination,
      information, personalized attention, and non-discrimination. We argue that, for
      patients to enjoy their rights in the hospital setting, a clear definition of
      roles and relationships and public education on strategies of asserting their
      rights without intimidation are necessary. It emerges that when patients' rights
      are denied, patients resort to retaliation by violating the dignity of the
      nurses. This jeopardizes the envisaged mutual support in the nurse-patient
      relationship and compromises patient satisfaction.

PMID- 21178194
TI  - Human rights consequences of mandatory HIV screening policy of newcomers to
      Canada.
AB  - This paper focuses on the key human rights consequences of the HIV screening
      policy that applies to all permanent and some temporary resident applicants to
      Canada. This mandatory policy was introduced in early 2002 by Citizenship and
      Immigration Canada after consultation with Health Canada. The policy has yet to
      be evaluated and, until recently, the actualities of the medical encounters where
      testing occurs in domestic and international settings have not been researched.
      There is no systematic documentation of the policy's implications on either the
      lives of persons who submit to mandatory testing or on health systems. This
      article argues that there are sound options for responding to the human rights
      challenges posed by the screening policy. Data were obtained from secondary
      literature and findings from empirical fieldwork and research among immigrants
      living with HIV/AIDS in Canada. This paper adds to theoretical and applied health
      services and interventions work by focusing attention on avenues for addressing
      key human rights concerns posed by the policy. These are identified and
      critically explored through the framework that Lawrence Gostin and the late
      Jonathan Mann developed in 1999, which was later extended by Barry Hoffmaster and
      Ted Schrecker in 2000. The article concludes with four recommendations for
      addressing the central human rights consequences of the policy.

PMID- 21178195
TI  - Sex trafficking and health care in Metro Manila: identifying social determinants
      to inform an effective health system response.
AB  - This social science case study examines the sex trafficking of women and girls in
      Metro Manila through a public health lens. Through key informant interviews with
      51 health care and anti-trafficking stakeholders in Metro Manila, this study
      reports on observations about sex trafficking in Metro Manila that provide
      insight into understanding of risk factors for sex trafficking at multiple levels
      of the social environment: individual (for example, childhood abuse), socio
      cultural (for example, gender inequality and a "culture of migration"), and macro
      (for example, profound poverty caused, inter alia, by environmental degradation
      disrupting traditional forms of labor). It describes how local health systems
      currently assist sex-trafficking victims, and provides a series of
      recommendations, ranging from prevention to policy, for how health care might
      play a larger role in promoting the health and human rights of this vulnerable
      population.

PMID- 21178196
TI  - [Tactics of surgical treatment of patients with complicated peptic ulcer
      disease].
AB  - Article presents the results of medical treatment after peptic ulcer surgery. I
      group--59 patients with late complications after peptic ulcer surgery and II
      group--16 patients with complications of peptic ulcer disease, operated in
      presence of absolute indications. 13C-UBT and RUT of biopsy material were used to
      diagnose Hp infection. Hp positive patients received antibacterial treatment.
      After 1 month from the end of therapy and 1 year after Hp eradication control
      investigations by 13C-UBT and endoscopy were performed. 77.3% of all and 84.4% of
      early non treated patients were Hp positive. All patients (of I and II gr.), who
      followed control testing after antibacterial treatment were finally detected as
      Hp negative. In I group, control endoscopy revealed epitelization or scarring of
      ulcer and reduction of inflammatory changes in gastric and duodenal mucosa in all
      44 cases of eradication of Hp infection (in 2 patients with peptic ulcer of GEA
      ulcer relapsed in later). In II group, in 8 patients, who received antibacterial
      treatment additionally to surgical method, any late complications after surgery
      were not revealed. In other 6 Hp positive patients: 2--ulcer recurrence and 2-
      development of chronic gastritis of operated stomach were noted, which required
      the treatment of Hp infection in future. It is concluded that 1)surgery does not
      change Hp-status of patients and Hp infection retains in more than 80% of cases;
      2) ulcer recurrence, chronic gastritis of operated stomach or its stump are
      associated with Hp and regress after Hp eradication; 3) progression of gastritis
      into atrophic remain after surgery, which increases risk of cancer development
      and there is possibility of its regression after antibacterial treatment of Hp
      infection. The recommendations were worked out: 1) perforated, bleeding or
      stenosing ulcer must be treated only by ulceroraphy, suturing or pyloroplasty
      respectively, added with subsequent Hp eradication therapy for the prevention of
      late complications after peptic ulcer surgery; 2) vagotomy or partial gastrectomy
      must be a forced intervention in cases of decompensate pylorostenosis, resistant
      to treatment ulcers, as ulcers non-healing or recurring after adequate
      conservative treatment. Subsequent verification and eradication of Hp infection
      are necessary.

PMID- 21178198
TI  - [Original method of cesarean section operation and its role in the prevention of
      obstetric complications].
AB  - The authors made an analysis of archival material of 1577 case histories of the
      patients who were subjected to cesarean section operation at Tbilisi Experimental
      Maternity Hospital and at "The House of Health" during 1999-2000 years. The case
      histories were divided into two groups: 1474 patients made 1--main group which
      were subjected to the operation of cesarean section according to modified method
      offered by Professor A. Koridze, while 103 patients operated according to
      traditional method accepted at present time made the 11--control group. The
      authors made clinical-laboratory analysis of the investigated case histories and
      came to a conclusion that the use of the offered method of cesarean section
      operation in obstetric practice will give the possibility to decrease
      postoperation complications and, correspondingly, the introduction of the given
      method is completely justified.

PMID- 21178197
TI  - Novelties in treatment approach of poly-neoplasias developed during thyroid
      pathologies.
AB  - In publication were discussed pathogenic mechanisms which are developed during
      concordance of malignant tumors of thyroid gland and reproductive systems and
      dishormonal hyperplasias, also functional disturbances which accompany thyroid
      gland diseases and principles of treatment during synchronic and metachronic
      manifestations. The treatment of polyneoplasias by "neurotransmitive control" is
      proposed. Importance of thyroid suppressive therapy was assessed. The efficacy of
      thyrotrophic hormone suppression by neurotransmitters in prevention of malignant
      tumors of reproductive system was reported.

PMID- 21178199
TI  - [Evaluation of the effectiveness of the modified method of cesarean section
      operation with the method of ultrasonography research].
AB  - On the basis of retrospective analysis of 160 clinical cases, the effectiveness
      of the modified method of cesarean section operation with the ultrasonography and
      immunological technique has been evaluated. Clinical-ultrasonography analysis
      proved that evolution rate after using of traditional method of cesarean section
      is markedly behind in comparison with the results received in the patients of
      main group. At the same time, the changes in echo-parameters prevailed the
      clinical manifestations which allow to carry out preventive measures in proper
      time and correspondingly to avoid the possible complications.

PMID- 21178200
TI  - [Parameters of innate immunity in clinically manifested and subclinic forms of
      infections caused by hepatitis B and C viruses].
AB  - The authors determined parameters of innate immunity (IIM) in patients with acute
      and chronic forms of viral hepatitis B and C and in persons with subclinic
      infections caused by hepatitis B and C viruses.The results obtained demonstrated
      that clinically manifested (acute and chronic) and subclinic forms of infections
      caused by hepatitis B and C viruses were accompanied by development of IIM
      depression. At the same time the signs of IIM's depression in patients with
      clinically manifested forms of infections were expressed in higher degree than in
      persons with subclinical forms of infections.

PMID- 21178201
TI  - [The evaluation of nitrogen metabolism and the reactivity of the organism in
      patients with dry skin].
AB  - It is known that in norm horny layer of the epidermis is able to retain water due
      to the presence of hygroscopic substances inside corneocytes in the form of so
      called natural moisturizing factors (NMF), consisting of free amino acids and
      their derivatives, which are formed during the decay of filaggrin as well as
      lactic acid, urea, sugars, and intercellular lipid membranes, creating a barrier
      that prevents transepidermal water loss. At the same time, the results of recent
      studies have shown that urea--a kind of natural antioxidant that protects tissues
      from the accumulation of aggressive forms of oxygen. It is able to stabilize the
      lysosomal membranes, thus preventing autolysis of cells. The ability of urea at
      low concentrations to modify the reactivity of functional groups of proteins
      leads to conformational changes of immunoglobulin, which has an inhibitory effect
      on the immune system, including the diminishing impact on the development of
      reaginic type reactions. Urea has anti-inflammatory, hyposensitizing, and
      antioxidant effect. Based on the above the aim of this study was to determine the
      content of urea and some indicators of cellular and humoral immunity in case of
      chronic dermatoses, accompanied by dryness of the skin. Indicators of nitrogen
      metabolism of blood serum (urea. ammonia), some parameters of cellular and
      humoral immunity were studied in 27 patients, who according to nosological units
      were distributed as follows: atopic dermatitis (12), psoriasis (7), xerosis (8).
      In the study of the concentration of urea in the blood, and some indicators of
      cellular immunity, as well as the content of immunoglobulin E in the blood of our
      patients a decrease in the number of T--lymphocytes, mainly due to T--suppressor
      and raising the level of immunoglobulin E have been revealed. Specific patterns
      of changes in these parameters, depending on nosological unit, severity of
      disease and degree of dryness of the skin have also been observed.

PMID- 21178202
TI  - Traditional Chinese medicine in diagnosis and treatment of fibromyalgia syndrome.
AB  - Fibromyalgia Syndrome (FS) is known for the difficulties arising from
      classification. The accompanying pain in skeletal muscles, myofascial peri
      articular structures and a number of polymorphic symptoms cannot be separated
      into complexes of symptoms. The application of principles of Traditional Chinese
      Medicine (TCM) helps in analyzing the symptoms of FS to detect a leading syndrome
      and thereby establish an individual therapy. Medical histories and objective
      examinations of 25 patients with FS and 22 patients with vertebrogenic pain
      syndromes were analyzed according to TCM. A questionnaire was used to determine
      the leading constitutional type according to the 5-elements-theory. Analyses of
      the results showed that 83% of patients with FS were of constitutional type of
      the element earth. The following syndromes were found to be important in FS: 1)
      liver-Qi-stagnation, 2) Yin and blood deficiency of the liver, 3) Yang-weakness
      of the spleen and kidney, 4) Yin-weakness of the kidney. Applying TCM for FS
      allows for separating a group of symptoms and thus individual therapy. The
      determination of the constitutional type according to the 5-elements-theory may
      be used for a better understanding of the disharmony pattern.

PMID- 21178203
TI  - Heterogeneity and gene-geography of beta-thalassemia in Georgia.
AB  - Georgia is situated between 44 degrees  and 41 degrees  of Northern Width. This
      is an area which belongs to "Malarial zone" of the Earth. This country is
      characterized by peculiar geographic contrasts as well as by peculiar ethnic
      variety of population on the small territory. So it represents an important
      region for study of thalassemias. The main purpose of this work is to present
      nonpublished results of long-term clinical and population investigations for
      study of heterogeneity and gene-geography of beta-thalassemia in Georgia. About
      11.428 practically healthy persons were investigated in different Georgian and
      non-Georgian ethno-territorial groups under expeditionary conditions and about
      600 patients (probands and members of their families)--in clinical laboratory.
      Screening tests under expeditionary conditions and special tests for the
      differentiation of thalassemias in clinical laboratory as well as familial
      genetic investigaton were performed for diagnostics of thalassemias. Common form
      of beta-thalassemia in Georgia was found beta(A2)--thalassemia wich was revealed
      not only in Georgian families but also among Azerbaijanians,
      Armenians,Daghestanians, Greeks, Georgian Jews, leaving in this country. Very
      rare deltabeta(F)--thalassemia was also revealed. From genetic point of view most
      heterogenous was found thalassemia intermedia, due to different combinations of
      alpha, beta,deltabeta--thalassemias. Population study revealed regularities of
      gene-geography of beta-thalassemia in Georgia: a) statistical significantly
      higher gene frequency in lowlands and valleys than in highlands, b) Difference of
      gene frequency in Georgian and non-Georgian ethnic groups in similar geographic
      conditions, c) Direct correlation between beta-thalassemia gene frequency and
      degree of malariogeneity of territory, d) Direct correlation between beta
      thalassemia gene frequency and intensity of former malaria focuses, e) Direct
      correlation between gene frequency and p. vivax distribution area (in the past).
      Gene-geographic card of "Distribution of beta-thalassemia gene in ethno
      territorial groups and malariogenic zones of Georgia" was made up. By means of
      this cord beta-thalassemia gene frequency at non-investigated territories of
      Georgia was prognosed. Prognosis justified. Also this card may be recommended for
      use in other countries taking into consideration malaria distribution (even in
      the past) as well as ethnic structure of population.

PMID- 21178204
TI  - Composition of erythrocytic (ABO, Rh-Hr, Kell, MN) group antigens characteristic
      of the Ozurgeti district's population.
AB  - Erythrocytic group antigens represent a genetically stably determined trait.
      Investigation of antigens of the said system in different regions is of the
      greatest importance in terms of both the creation of demographic data of the
      region as well as practical medicine, especially for transplantology and
      transfusiology. The peripheral or venous blood of 232 local natives (healthy
      donors) of Ozurgeti district of Guria region has been taken as the test subject.
      The test subject was taken by random methods in different vilifies (Bakhvi,
      Mshvidobauri, Ozurgeti, Likhauri, Gurianta, Bokhvauri, Dvadzu, Pampaleti) To
      identify the ABO, Rh-Hr, Kell, MN system antigens, an express-method using
      monoclonal antibodies has been applied. In studying the ABO system, it was fixed
      that the highest distribution frequency was characteristic of the 0(I) group
      (52.3+/-3.2%), then follows the group A(II) (38.5+/-3.2%). The distribution
      frequency of the B(III) group is (8.2+/-1.8%) and that of AB(IV)--(0.8+/-0.5).
      The population's 85.2+/-2.32% is the carrier of the Rh+ phenotypic group, while
      14.7+/-2.3% belongs to the Rh-phenotypic group. In studying the concentration of
      alleles, the low concentration of p(K) allele was detected that equaled 0.2; the
      concentration of q(K) allele made 0.8, that of p(M)--0.65, and that of q (N) -
      035.

PMID- 21178205
TI  - [Gender differences in medical activities and self-evaluation of health status
      among people displaced from Abkhazia].
AB  - A growing scientific literature highlights concern about the influence of social
      bias in medical care. Differential treatment of male and female patients has been
      among the documented concerns. Yet, little is known about the extent to which
      differential treatment of male and female patients reflects the influence of
      social bias or of more acceptable factors, such as different patient preferences
      or different anticipated outcomes of care. This paper attempts to ascertain the
      underlying basis for an observed differential in physicians' tendency to advice
      activity restrictions for male and female patients. We explore the extent to
      which the gender-based treatment differential is attributable to: (1) patients'
      health profile, (2) patients' role responsibilities, (3) patients' illness
      behaviors, and (4) physician characteristics. These four categories of variables
      correspond to four prominent social science hypotheses concerning gender
      differences in health and health care utilization. Data are drawn from the
      longitudinal observational study more of the 2000 IDP patients from Abkhazia.
      Gender differences in illness behavior and medical activities of the patients
      both appear to contribute to the observed differential. Female patients exhibit
      more illness behavior than males, and these behaviors increase physicians'
      tendency to prescribe activity restrictions.

PMID- 21178206
TI  - [The radiation background and hygienic assessment of external irradiation doses
      of population in some mountainous regions of Georgia].
AB  - The radioecological situation of Mtskheta-Mtianeti region of Georgia has been
      studied. Doses from external irradiation were determined and estimated. The
      average value of radiation background (RB) of open areas in Mtskheta-Mtianeti
      region accounts 84.6 nGy/h, which is nearly equal to the average values in the
      countries of western Europe. This shows that investigated territories have high
      natural radiation background, which considering the geographical position and
      geophysical situation of Georgia is normal. The average value of radiation
      background of buildings in investigated territories accounts 120.4 nGy/h, which
      is little more than worldwide average value. The average annual dose from
      external irradiation (without radon component) for population of Mtskheta
      Mtianeti region accounts 0.99 mZv/y, which is slightly more than worldwide
      average value. Since approximately 2/3 of effective equivalent dose comes from
      internal radiation and 1/3--from external radiation, it's reasonable to suppose
      that the radiation load of population of Mtskheta-Mtianeti region is significant
      and requires implementation of radiation dose reduction measures.

PMID- 21178207
TI  - [Some aspects of classification and treatment strategy of iatrogenic bile duct
      injury].
AB  - Iatrogenic bile duct injury continues to be an important clinical problem,
      resulting in serious morbidity, and occasional mortality, to patients. None of
      the classification system is universally accepted and worldwide used as each has
      its own limitation. This article reviews the various classification systems of
      bile duct injury. Traditionally, biliary injuries have been classified using the
      Bismuth's classification. This classification does not encompass the whole
      spectrum of injuries during laparoscopic cholecystectomy. Strasberg's
      classification made Bismuth's classification much more comprehensive by including
      various other types of extrahepatic bile duct injuries. Our own classification is
      simple enough, embraces the majority possible variants of bile duct injuries and
      convenient in clinical use.

PMID- 21178208
TI  - Orexinergic system and pathophysiology of epilepsy.
AB  - Neuropeptids orexins, also known as the hypocretins, are expressed in the lateral
      hypothalamus. Orexin-containing cells project widely throughout the brains, are
      crucial for the regulation of wakefulness and dysfunction of this system is
      associated with pathophysiology of narcolepsy-cataplexy. Orexin neurons play an
      important role in motivation, feeding and adaptive behaviors. Distribution of
      orexinergic receptors in the hippocampus tended to the ideas that orexins might
      be involved in the functions relating to the hippocampus. Effects of neuropeptide
      orexin-A on epileptiform activity in hippocampal slices were investigated. 500 um
      thick hippocampal slices from 8-10 week-old rodents were used. Field excitatory
      postsynaptic potential (pop-fEPSP) and population spike in CA1 of hippocamopus
      were registered using standard protocol of in vitro electrophysiological
      experiments. Initial slope of the fEPSP and amplitude of II pop-spike were
      measured. Bursting neurons in CA3 were recorded in modified saline. We have found
      that orexin-A decreases duration/amplitude of multiple discharges of pop-spikes
      and inhibits spontaneous epileptiform afterdischarges induced by bicuculline
      methiodide in CA1. Orexin-A also modulates the frequency of discharges of
      bursting neurons in CA3. Our results suggest possible involvement of orexinergic
      system in antiepileptic action. Supported by ISTC Grant G-1318.

PMID- 21178209
TI  - [The level of fluoxetine in blood plasma and washed from eritrizite supernatant].
AB  - Antidepressant Fluoxetine and their major therapeutically active metabolite
      Norfluoxetine was monitored in albumene and glicoproteene of blood plasma and
      washed from eritrozite supernatant. In paper we describe rapid and reliable
      method using high-performance liquid chromatography for simultaneous measurement
      of plasma and supernatant concentration of Fluoxetine and Norfluoxetine. The
      described method has been successfully used in clinical and laboratory cases.
      Large interindividual variations in plasma and supernatan concentrations of
      Fluoxetine and their major metabolite have been shown. In albumene fractions of
      blood plasma the level of Fluoxetine is more higher then in supernatant. A
      successful development of the clinico-pharmacokinetic direction at the present
      stage is due to improvement and standardization of methods of clinical and
      pharmacokinetic examination which help to ensure a reliable pretreatment
      identification of patients potentially sensitive to pharmacotherapy with
      antidepressants.

PMID- 21178210
TI  - Quantitative changes of schwann and mast cells in the process of peripheral nerve
      regeneration.
AB  - One of the most common problems in the fields of orthopedic surgery and neurology
      is that of the injured peripheral nerve. Injured nerve fibers in the adult
      mammalian peripheral nervous system can and often do regenerate, thereby
      restoring at least some lost faunctions. During the past decade enormous progress
      has been made in the understanding of the cellular events and molecular changes
      during degeneration and regeneration of peripheral nerves. However, our knowledge
      of the regulatory mechanisms and signaling cascades underlying the complex
      molecular regeneration program is still very limited despite an enormous amount
      of new experimental data. Injure to peripheral nerve initiates a complex cascade
      of signals involving neurons, glia and cells of the immune system. The question
      of which cells are responsible for nerve survival and tissue repair mechanisms
      after injury remains controversial. Although it has largely been demonstrated
      that macrophages and Schwann cells play important roles in degrading and removing
      myelin few data have been reported regarding mast cells in Wallerian
      degeneration. The present study has been designed to evaluate the correlation
      between Schwann and mast cells during regeneration of the injured peripheral
      nerve. Animals were divided into two groups: experimental and intact rats. The
      left sciatic nerve was separated from the surrounding tissue, was transected in
      its mid-thigh portion and sewed up. Sewed sciatic nerves were obtained and used
      for morphological and Immunocytochemical observation 2 and 12 day, and 1 month
      after transection. Our experimental data reveals that the mast cells, as well as
      Schwann cells, play a pivotal role in regeneration process after injury. The
      correlation between the changes of quantity of schwann cells and mast cells
      during the regeneration of injured peripheral nerve was not revealed.

PMID- 21178211
TI  - Climate indices, rainfall onset and retreat, and malaria in Nigeria.
AB  - BACKGROUND & OBJECTIVES: Rainfall in western sub-Saharan Africa is related to
      seasonal shifts of the Inter-tropical Convergence Zone, which moves northward
      early in the year, retreating in the second half of the year. The objective of
      the present study was to determine significant relationships between onset and
      retreat timing and climate indices. The relationship between timing and malaria
      case reporting was then evaluated. METHODS: Relationships between published
      rainfall onset and retreat dates for Nigeria from 1971- 2000 were evaluated in
      relation to pairs of climate indices using response surface analysis. Graphical
      representation of the response surface in relation to the underlying data was
      used to identify instances of overfitting. Association of onset and retreat
      timing with published case reporting records was evaluated using graphical and
      correlation analysis. RESULTS: Onset timing and rate of advance were related to
      ENSO (El Nino-Southern Oscillation), in combination with the Northern Annular
      Mode (NAM), while retreat timing was related to NAO (North Atlantic Oscillation),
      in combination with the East Pacific (EP) or West Pacific (WP) index, depending
      on location. Later onset was associated with faster northward progression of
      onset. Retreat date at Kano, the most northerly of the study locations, increased
      over the period 1990-2000, with higher case reporting for Nigeria as a whole
      being associated with the last three years of that period. INTERPRETATION AND
      CONCLUSION: Rainfall retreat occurs much faster than onset, with onset and
      retreat timing and rate of onset advance being related to combinations of climate
      indices rather than to a single index. Threshold for determining a "rainy" day
      would influence results. The increase in national case reporting with delayed
      retreat at Kano may be related to the extension of the short transmission period
      in the north.

PMID- 21178212
TI  - Complete conservation of an immunogenic gene (lcr1) in Leishmania infantum and
      Leishmania chagasi isolated from Iran, Spain and Brazil.
AB  - BACKGROUND & OBJECTIVES: Kala-azar is the visceral and most severe form of
      leishmaniasis that leads to death if untreated. The causative agents of visceral
      leishmaniasis (VL) are members of Leishmania (L.) donovani complex which includes
      L. chagasi and L. infantum. Genome sequences have raised the question whether L.
      chagasi and L. infantum are synonymous or different. This question has important
      implications for clinical and epidemiological studies, evaluation of vaccines and
      drugs, and disease control. LCR1 is an immunogenic molecule discovered from L.
      chagasi with potential as a component of a Leishmania subunit vaccine. If this
      protein has potentials for being used in a vaccine or diagnostic testing, there
      should be little variability in this molecule between L. infantum isolates from
      diverse geographic regions. The aim of this study was to determine whether lcr1
      of an Iranian strain of L. infantum was identical to lcr1 of both L. infantum
      strain from a different geographic region (Spain) and that of an L. chagasi
      isolate from Brazil. METHODS: L. infantum isolated from an Iranian kala-azar
      patient was studied. Lcr1 from this isolate was PCR amplified, cloned, and
      studied by restriction digest analysis and sequencing. RESULTS: The sequences of
      lcr1 of the Iranian L. infantum were completely identical at nucleotide level to
      lcr1 sequences of both the Spanish L. infantum and the Brazilian L. chagasi
      strains. CONCLUSION: Complete conservation of the DNA sequence encoding for LCR1
      molecule between geographically distinct Leishmania species adds credibility to
      the potential for LCR1 as a component of a subunit vaccine and diagnostic test
      for kala-azar.

PMID- 21178213
TI  - Molecular epidemiology of Crimean- Congo hemorrhagic fever virus genome isolated
      from ticks of Hamadan province of Iran.
AB  - BACKGROUND & OBJECTIVES: Crimean-Congo hemorrhagic fever (CCHF) virus is a tick
      borne member of the genus Nairovirus, family Bunyaviridae. CCHFV has been
      isolated from at least 31 different tick species. The virus is transmitted
      through the bite of an infected tick, or by direct contact with CCHFV-infected
      patients or the products of infected livestock. This study was undertaken to
      study the genetic relationship and distribution of CCHFV in the tick population
      of Hamadan province of Iran. METHOD: In this study, RT-PCR has been used for
      detection of the CCHFV genome. RESULTS: This genome was detected in 19.2% of the
      ticks collected from livestock of different regions of the Hamadan province in
      western Iran. The infected species belonged to Hyalomma detritum, H. anatolicum,
      Rhipicephalus sanguineus and Argas reflexus. With one exception, genetic analysis
      of the virus genome isolates showed high sequence identity to each other. Even
      though they clustered in the same group with the strain circulating in Iran, they
      had a closer relationship to the Matin strain. INTERPRETATION & CONCLUSION:
      Vector control programs should be applied for reducing population density of
      potential tick vectors in this province. Further surveys are indicated in this
      region to provide a better view of the distribution and epidemiology of the
      virus.

PMID- 21178214
TI  - Estimating a mosquito repellent's potential to reduce malaria in communities.
AB  - BACKGROUND & OBJECTIVES: Probability models for assessing a mosquito repellent's
      potential to reduce malaria transmission are not readily available to public
      health researchers. To provide a means for estimating the epidemiological
      efficacy of mosquito repellents in communities, we developed a simple
      mathematical model. STUDY DESIGN: A static probability model is presented to
      simulate malaria infection in a community during a single transmission season.
      The model includes five parameters- sporozoite rate, human infection rate, biting
      pressure, repellent efficacy, and product-acceptance rate. INTERVENTIONS: The
      model assumes that a certain percentage of the population uses a personal
      mosquito repellent over the course of a seven-month transmission season and that
      this repellent maintains a constant rate of protective efficacy against the bites
      of malaria vectors. MAIN OUTCOME MEASURES: This model measures the probability of
      evading infection in circumstances where vector biting pressure, repellent
      efficacy, and product acceptance may vary. [corrected] RESULTS & CONCLUSION:
      Absolute protection using mosquito repellents alone requires high rates of
      repellent efficacy and product acceptance. [corrected] Using performance data
      from a highly effective repellent, the model estimates an 88.9% reduction of
      infections over a seven- month transmission season. A corresponding reduction in
      the incidence of super-infection in community members not completely evading
      infection can also be presumed. Thus, the model shows that mass distribution of a
      repellent with >98% efficacy and >98% product acceptance would suppress new
      malaria infections to levels lower than those achieved with insecticide treated
      nets (ITNs). A combination of both interventions could create synergies that
      result in reductions of disease burden significantly greater than with the use of
      ITNs alone.

PMID- 21178215
TI  - Bedbug infestation and its control practices in Gbajimba: a rural settlement in
      Benue state, Nigeria.
AB  - BACKGROUND & OBJECTIVES: The common bedbug Cimex lectularius Linnaeus 1758
      (Hemiptera: Cimicidae) is a globally re-emerging pest of serious public health
      concern. We investigated bedbug infestation in randomly selected apartments in
      Gbajimba community in Guma Local Government area in Benue state, Nigeria.
      METHODS: Beddings and furniture (bed frames, pillows, mattresses, cushion chairs,
      mats, mosquito nets and bamboo beds) were thoroughly inspected for bedbug
      infestation using the hand-picking technique. Data were analysed using chi-
      square analysis for differences in the infestation levels in harbourages and
      sampling locations. RESULTS: Only 16% of the apartments investigated showed no
      evidence of bedbug infestation as egg cases and faecal marks were sighted in
      62.2% of apartments surveyed. The highest infestation rate was observed in Angwan
      Jukun area and infestation here was higher compared to other study locations
      within the town though the difference was not statistically significant (x2 =
      7.92, df = 6, p >0.05). Bamboo beds harboured the highest number of bedbugs
      collected, accounting for 35.8%, while other harbourages like iron bed frames and
      sleeping mats had 23 and 22.7% infestation rates respectively. The infestation
      rates in these household items were significantly higher than other items
      inspected (x2 = 11.8, df = 4, p > 0.05). INTERPRETATION & CONCLUSION: This study
      demonstrates the urgent need for identification of evidences of infestation and
      bedbug management involving community participation in inspection, detection and
      education, including physical removal and exclusion as well as pesticide
      application.

PMID- 21178216
TI  - Epidemiology and control of Schistosomiasis and other intestinal parasitic
      infections among school children in three rural villages of south Saint Lucia.
AB  - OBJECTIVE: The purpose of this study was to determine the epidemiology of
      parasitic infections and the efficacy of treatment among school children in rural
      villages of south Saint Lucia. METHOD: A total of 554 school children
      participated in this study. Parasitic infections were confirmed by using Kato-
      Katz method. RESULTS & CONCLUSION: Overall, 61.6% of the school children were
      infected by any parasitic infection. The helminths identified were Ascaris
      lumbricoides (15.7%), Hookworm (11.9%), Strongyloides (9.7%), Trichuris trichiura
      (4.7%), Schistosoma mansoni (0.6%), Taenia solium (0.8%) and Enterobius
      vermicularis (2.1%), Entamoeba coli (9.7%), Iodameba butschlii (5%), Entamoeba
      histolytica (1.1%), Giardia lamblia (1.8%) and Endolimax nana (2.1%). The control
      intervention included treatment with albendazole 400 mg and praziquantel 40 mg/kg
      as well as awareness campaigns. Post-interventional assessment showed the total
      prevalence of intestinal parasitic infection reduced from 61.6 to 3.6% with a
      cure rate of 94.2%, following the control methods.

PMID- 21178217
TI  - A study of treatment seeking behaviour for malaria and its management in febrile
      children in rural part of desert, Rajasthan, India.
AB  - BACKGROUND & OBJECTIVES: For management of malaria, there is a need to give
      attention on specific group of people like children >5 yr of age in the
      community. They are unable to explain their feelings about severity of illness
      and effects of treatment on health and they are dependent on others for their
      health care, therefore, it is the mother who can seek, obtain, and use medication
      appropriately. This is directly linked to the level of education, socioeconomic
      status, timely decision, accessibility of health facility, correct use of drugs
      and their follow- up. The present study was undertaken with the aim to know the
      basis on which malaria was recognized and classified and exploring factors
      involved in the selection of different treatment options in the desert population
      of Rajasthan. METHODS: Interview and observation techniques were used for data
      collection in 15 villages of Ramgarh PHC in Jaisalmer district of Rajasthan
      state, India. A total of 164 mothers were interviewed and observations were made
      by the investigators in the group discussions who utilized health facility for
      the febrile children < 5 yr of age. RESULTS: More than 93.3% mothers started
      taking care at home for their febrile children and watched for improvement on an
      average up to 72 h. When they thought there was no hope to manage the case at
      their level, they shifted their febrile children to the nearest health facility
      such as sub-centre/PHC/private health practitioner. Utilization of health
      facility was linked with the age of the child, with younger children (<24 months
      of age) being significantly more likely to be utilized nearby health facility
      than 24- 59 months children. Children judged as severely ill by their mothers
      utilized health facility significantly more often than those not thought to be
      severely ill. Mothers from households where the household heads had a primary or
      secondary education were more likely to utilize health facility than those
      household heads having no education. Similarly, mothers from households with
      moderate or high income utilized health facility more frequently than those with
      low income. INTERPRETATION & CONCLUSION: The study revealed that mothers usually
      tried to manage febrile cases at their own level at home for children >5 yr of
      age. They had gone through different treatment options before utilizing health
      facilities. There was, on an average three days delay in seeking care in the
      remote villages of desert part of Rajasthan. To minimize the delay in diagnosis
      and treatment of malaria among the children >5 yr of age is an urgent need for
      intervening through IEC programme and trained volunteers for the management of
      malaria cases at village-level.

PMID- 21178218
TI  - Community awareness, perceptions, acceptability and preferences for using LLIN
      against malaria in villages of Uttar Pradesh, India.
AB  - BACKGROUND & OBJECTIVES: Long-lasting insecticidal nets (LLINs) have been
      introduced in India recently into the vector control programme. A study was
      undertaken to assess the community perception regarding use of LLIN, their
      acceptability, collateral benefits, etc. in certain villages of District Gautam
      Budh Nagar, Uttar Pradesh, India where LLINs are in use by the community. METHOD:
      A randomized community-based survey was undertaken during April- May 2009
      covering 596 respondents in LLIN villages where LLINs have been distributed along
      with 307 respondents in untreated net villages where untreated nets were
      distributed using structured questionnaire. Qualitative data were collected and
      the difference in proportion was calculated by z-test. RESULTS: A substantial
      number of respondents had good knowledge of the symptoms of malaria. According to
      respondents, LLINs were very much effective in bringing down the malaria
      incidence in their families. About 98.3% of the respondents asserted the use of
      LLINs as their use not only reduced the number of mosquitoes as well as other non
      target insects, but also reduced the malaria incidence. About 93.2% of the
      respondents were ready to purchase LLINs if available at nominal prices. All the
      respondents were satisfied about the performance of the LLINs in reducing the
      mosquito nuisance, safety of use and collateral benefits in LLIN villages.
      CONCLUSION: LLINs are safe, socially acceptable and should be promoted for vector
      control to reduce the disease burden in the communities.

PMID- 21178219
TI  - Predictors of knowledge of selected mosquito-borne diseases among adults of
      selected peri- urban areas of Puducherry.

PMID- 21178220
TI  - Larvicidal properties of cashew nut shell liquid (Anacardium occidentale L) on
      immature stages of two mosquito species.

PMID- 21178221
TI  - Subhyaloid hemorrhage in cerebral malaria.

PMID- 21178222
TI  - Plasmodium vivax with acute glomerulonephritis in an 8- year old--queries.

PMID- 21178223
TI  - Freestanding silicon quantum dots: origin of red and blue luminescence.
AB  - In this paper, we studied the behavior of silicon quantum dots (Si-QDs) after
      etching and surface oxidation by means of photoluminescence (PL) measurements,
      Fourier transform infrared spectroscopy (FTIR) and electron paramagnetic
      resonance spectroscopy (EPR). We observed that etching of red luminescing Si-QDs
      with HF acid drastically reduces the concentration of defects and significantly
      enhances their PL intensity together with a small shift in the emission spectrum.
      Additionally, we observed the emergence of blue luminescence from Si-QDs during
      the re-oxidation of freshly etched particles. Our results indicate that the red
      emission is related to the quantum confinement effect, while the blue emission
      from Si-QDs is related to defect states at the newly formed silicon oxide
      surface.

PMID- 21178224
TI  - Integrated freestanding single-crystal silicon nanowires: conductivity and
      surface treatment.
AB  - Integrated freestanding single-crystal silicon nanowires with typical dimension
      of 100 nm * 100 nm * 5 um are fabricated by conventional 1:1 optical lithography
      and wet chemical silicon etching. The fabrication procedure can lead to wafer
      scale integration of silicon nanowires in arrays. The measured electrical
      transport characteristics of the silicon nanowires covered with/without SiO(2)
      support a model of Fermi level pinning near the conduction band. The I-V curves
      of the nanowires reveal a current carrier polarity reversal depending on Si
      SiO(2) and Si-H bonds on the nanowire surfaces.

PMID- 21178225
TI  - Non-aqueous synthesis of water-dispersible Fe3O4-Ca3(PO4)2 core-shell
      nanoparticles.
AB  - The Fe(3)O(4)-Ca(3)(PO(4))(2) core-shell nanoparticles were prepared by one-pot
      non-aqueous nanoemulsion with the assistance of a biocompatible triblock
      copolymer, poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene
      glycol) (PEO-PPO-PEO), integrating the magnetic properties of Fe(3)O(4) and the
      bioactive functions of Ca(3)(PO(4))(2) into single entities. The Fe(3)O(4)
      nanoparticles were pre-formed first by thermal reduction of Fe(acac)(3) and then
      the Ca(3)(PO(4))(2) layer was coated by simultaneous deposition of Ca(2+) and
      PO(4)(3-). The characterization shows that the combination of the two materials
      into a core-shell nanostructure retains the magnetic properties and the
      Ca(3)(PO(4))(2) shell forms an hcp phase (a = 7.490 A, c = 9.534 A) on the
      Fe(3)O(4) surface. The magnetic hysteresis curves of the nanoparticles were
      further elucidated by the Langevin equation, giving an estimation of the
      effective magnetic dimension of the nanoparticles and reflecting the enhanced
      susceptibility response as a result of the surface covering. Fourier transform
      infrared (FTIR) analysis provides the characteristic vibrations of
      Ca(3)(PO(4))(2) and the presence of the polymer surfactant on the nanoparticle
      surface. Moreover, the nanoparticles could be directly transferred to water and
      the aqueous dispersion-collection process of the nanoparticles was demonstrated
      for application readiness of such core-shell nanostructures in an aqueous medium.
      Thus, the construction of Fe(3)O(4) and Ca(3)(PO(4))(2) in the core-shell
      nanostructure has conspicuously led to enhanced performance and multi
      functionalities, offering various possible applications of the nanoparticles.

PMID- 21178226
TI  - Nanotexturing of GaN light-emitting diode material through mask-less dry etching.
AB  - We describe a new technique for random surface texturing of a gallium nitride
      (GaN) light-emitting diode wafer through a mask-less dry etch process. This
      involves depositing a sub-monolayer film of silica nanospheres (typical diameter
      of 200 nm) and then subjecting the coated wafer to a dry etch process with
      enhanced physical bombardment. The silica spheres acting as nanotargets get
      sputtered and silica fragments are randomly deposited on the GaN epi-layer.
      Subsequently, the reactive component of the dry etch plasma etches through the
      exposed GaN surface. Silica fragments act as nanoparticles, locally masking the
      underlying GaN. The etch rate is much reduced at these sites and consequently a
      rough topography develops. Scanning electron microscopy (SEM) and atomic force
      microscopy (AFM) inspections show that random topographic features at the scale
      of a few tens of nanometres are formed. Optical measurements using angle-resolved
      photoluminescence show that GaN light-emitting diode material thus roughened has
      the capability to extract more light from within the epilayers.

PMID- 21178227
TI  - Controlled in situ nanoscale enhancement of gold nanowire arrays with plasmonics.
AB  - The controlled in situ growth of ordered gold nanoparticles and nanowire arrays
      has been studied by optically tracking changes in the local surface plasmon
      resonance (LSPR) spectrum. A spectrometer and custom-programmed analysis software
      track changes in the LSPR spectrum. The peak position, peak height (i.e.
      extinction intensity) and peak width (e.g. radius of curvature) were tracked over
      time to quantify the dynamic growth of gold as soon as the system was exposed to
      a commercial gold enhancement solution. This enables the controlled dynamic
      growth of nano-objects without the necessity of characterizing the growth and
      aggregation kinetics of the gold enhancement solution. The result was the
      successful enhancement of their electrically conductive and plasmonic properties,
      as well as the controlled growth and transformation of line-patterned
      nanoparticles into conductive particle-based nanowires.

PMID- 21178228
TI  - Room-temperature Coulomb staircase in semiconducting InP nanowires modulated with
      light illumination.
AB  - Detailed electron transport analysis is performed for an ensemble of conical
      indium phosphide nanowires bridging two hydrogenated n(+)-silicon electrodes. The
      current-voltage (I-V) characteristics exhibit a Coulomb staircase in the dark
      with a period of ~ 1 V at room temperature. The staircase is found to disappear
      under light illumination. This observation can be explained by assuming the
      presence of a tiny Coulomb island, and its existence is possible due to the large
      surface depletion region created within contributing nanowires. Electrons tunnel
      in and out of the Coulomb island, resulting in the Coulomb staircase I-V.
      Applying light illumination raises the electron quasi-Fermi level and the
      tunneling barriers are buried, causing the Coulomb staircase to disappear.

PMID- 21178229
TI  - Shape and size control of InAs/InP (113)B quantum dots by Sb deposition during
      the capping procedure.
AB  - The role of Sb atoms present on the growth front during capping of InAs/InP
      (113)B quantum dots (QDs) is investigated by cross-sectional scanning tunnelling
      microscopy, atomic force microscopy, and photoluminescence spectroscopy. Direct
      capping of InAs QDs by InP results in partial disassembly of InAs QDs due to the
      As/P exchange occurring at the surface. However, when Sb atoms are supplied to
      the growth surface before InP capping layer overgrowth, the QDs preserve their
      uncapped shape, indicating that QD decomposition is suppressed. When
      GaAs(0.51)Sb(0.49) layers are deposited on the QDs, conformal growth is observed,
      despite the strain inhomogeneity existing at the growth front. This indicates
      that kinetics rather than the strain plays the major role during QD capping with
      Sb compounds. Thus Sb opens up a new way to control the shape of InAs QDs.

PMID- 21178230
TI  - Temperature dependence of graphene oxide reduced by hydrazine hydrate.
AB  - Graphene oxide (GO) was successfully prepared by a modified Hummer's method. The
      reduction effect and mechanism of the as-prepared GO reduced with hydrazine
      hydrate at different temperatures and time were characterized by x-ray
      photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR),
      elemental analysis (EA), x-ray diffractions (XRD), Raman spectroscopy and thermo
      gravimetric analysis (TGA). The results showed that the reduction effect of GO
      mainly depended on treatment temperature instead of treatment time. Desirable
      reduction of GO can only be obtained at high treatment temperature. Reduced at 95
      degrees C for 3 h, the C/O atomic ratio of GO increased from 3.1 to 15.1, which
      was impossible to obtain at low temperatures, such as 80, 60 or 15  degrees C,
      even for longer reduction time. XPS, 13C NMR and FTIR results show that most of
      the epoxide groups bonded to graphite during the oxidation were removed from GO
      and form the sp(2) structure after being reduced by hydrazine hydrate at high
      temperature (>60  degrees C), leading to the electric conductivity of GO
      increasing from 1.5 * 10(-6) to 5 S cm(-1), while the hydroxyls on the surface of
      GO were not removed by hydrazine hydrate even at high temperature. Additionally,
      the FTIR, XRD and Raman spectrum indicate that the GO reduced by hydrazine
      hydrate can not be entirely restored to the pristine graphite structures. XPS and
      FTIR data also suggest that carbonyl and carboxyl groups can be reduced by
      hydrazine hydrate and possibly form hydrazone, but not a C = C structure.

PMID- 21178231
TI  - Photoluminescent silicon quantum dots in core/shell configuration: synthesis by
      low temperature and spontaneous plasma processing.
AB  - Quantum confinement in zero-dimensional silicon nanocrystals (nC) in the quantum
      dot (QD) configuration has triggered a tremendous interest in nanostructured
      device technology. However, the formation of Si-QDs eventually proceeds through
      multi-step routes and involves high temperature processing that impedes preferred
      device configuration. The present work demonstrates the formation of nC-Si QDs of
      controlled size, density and distribution through one-step and spontaneous plasma
      processing, at a low substrate temperature (300  degrees C) compatible for device
      fabrication. Direct growth of nC-Si/SiO(x) core/shell quantum dots embedded in
      the a-Si matrix, 6.4-3.7 nm in diameter and with number density in the range ~ 6
      * 10(9)-1 * 10(11) cm(-2) has been accomplished, following a novel route where He
      dilution to SiH(4) in RF plasma CVD has been found instrumental. On gradual
      reduction in the size of QDs, splitting of the energy bands widens the optical
      band gap and induces visible photoluminescence that appears controllable by
      tuning the size and density of the dots. This low temperature and spontaneous
      plasma processing of nC-Si/SiO(x) core/shell QDs that exhibit the quantum size
      effect in photoluminescence is being reported for the first time.

PMID- 21178232
TI  - A quantum optical transistor with a single quantum dot in a photonic crystal
      nanocavity.
AB  - Laser and strong coupling can coexist in a single quantum dot (QD) coupled to a
      photonic crystal nanocavity. This provides an important clue towards the
      realization of a quantum optical transistor. Using experimentally realistic
      parameters, in this work, theoretical analysis shows that such a quantum optical
      transistor can be switched on or off by turning on or off the pump laser, which
      corresponds to attenuation or amplification of the probe laser, respectively.
      Furthermore, based on this quantum optical transistor, an all-optical measurement
      of the vacuum Rabi splitting is also presented. The idea of associating a quantum
      optical transistor with this coupled QD-nanocavity system may achieve images of
      light controlling light in all-optical logic circuits and quantum computers.

PMID- 21178233
TI  - Lateral interdot carrier transfer in an InAs quantum dot cluster grown on a
      pyramidal GaAs surface.
AB  - InAs quantum dot clusters (QDCs), which consist of three closely spaced QDs, are
      formed on nano-facets of GaAs pyramidal structures by selective-area growth using
      metal-organic chemical vapor deposition. Photoluminescence (PL) and time-resolved
      PL (TRPL) experiments, measured in the PL linewidth, peak energy and QD emission
      dynamics indicate lateral carrier transfer within QDCs with an interdot carrier
      tunneling time of 910 ps under low excitation conditions. This study demonstrates
      the controlled formation of laterally coupled QDCs, providing a new approach to
      fabricate patterned QD molecules for optical computing applications.

PMID- 21178234
TI  - Flower-shaped gold nanoparticles: synthesis, characterization and their
      application as SERS-active tags inside living cells.
AB  - The detection of Raman signals inside living cells is a topic of great interest
      in the study of cell biology mechanisms and for diagnostic and therapeutic
      applications. This work presents the synthesis and characterization of flower
      shaped gold nanoparticles and demonstrates their applicability as SERS-active
      tags for cellular spectral detection. The particles were synthesized by a facile,
      rapid new route that uses ascorbic acid as a reducing agent of gold salt. Two
      triarylmethane dyes which are widely used as biological stains, namely malachite
      green oxalate and basic fuchsin, were used as Raman-active molecules and the
      polymer mPEG-SH as capping material. The as-prepared SERS-active nanoparticles
      were tested on a human retinal pigment epithelial cell line and found to present
      a low level of cytotoxicity and high chemical stability together with SERS
      sensitivity down to picomolar particle concentrations.

PMID- 21178235
TI  - Optimizing deep hyperthermia treatments: are locations of patient pain complaints
      correlated with modelled SAR peak locations?
AB  - During deep hyperthermia treatment, patient pain complaints due to heating are
      common when maximizing power. Hence, there exists a good rationale to investigate
      whether the locations of predicted SAR peaks by hyperthermia treatment planning
      (HTP) are correlated with the locations of patient pain during treatment. A
      retrospective analysis was performed, using the treatment reports of 35 patients
      treated with deep hyperthermia controlled by extensive treatment planning. For
      various SAR indicators, the average distance from a SAR peak to a patient
      discomfort location was calculated, for each complaint. The investigated V(0.1
      closest) (i.e. the part of the 0.1th SAR percentile closest to the patient
      complaint) performed the best, and leads to an average distance between the SAR
      peak and the complaint location of 3.9 cm. Other SAR indicators produced average
      distances that were all above 10 cm. Further, the predicted SAR peak location
      with V(0.1) provides a 77% match with the region of complaint. The current study
      demonstrates that HTP is able to provide a global indication of the regions where
      hotspots during treatment will most likely occur. Further development of this
      technology is necessary in order to use HTP as a valuable toll for objective and
      advanced SAR steering. The latter is especially valid for applications that
      enable 3D SAR steering.

PMID- 21178236
TI  - The accuracy of dose calculations by anisotropic analytical algorithms for
      stereotactic radiotherapy in nasopharyngeal carcinoma.
AB  - Nasopharyngeal tumors are commonly treated with intensity-modulated radiotherapy
      techniques. For photon dose calculations, problems related to loss of lateral
      electronic equilibrium exist when small fields are used. The anisotropic
      analytical algorithm (AAA) implemented in Varian Eclipse was developed to replace
      the pencil beam convolution (PBC) algorithm for more accurate dose prediction in
      an inhomogeneous medium. The purpose of this study was to investigate the
      accuracy of the AAA for predicting interface doses for intensity-modulated
      stereotactic radiotherapy boost of nasopharyngeal tumors. The central axis depth
      dose data and dose profiles of phantoms with rectangular air cavities for small
      fields were measured using a 6 MV beam. In addition, the air-tissue interface
      doses from six different intensity-modulated stereotactic radiotherapy plans were
      measured in an anthropomorphic phantom. The nasopharyngeal region of the phantom
      was especially modified to simulate the air cavities of a typical patient. The
      measured data were compared to the data calculated by both the AAA and the PBC
      algorithm. When using single small fields in rectangular air cavity phantoms,
      both AAA and PBC overestimated the central axis dose at and beyond the first few
      millimeters of the air-water interface. Although the AAA performs better than the
      PBC algorithm, its calculated interface dose could still be more than three times
      that of the measured dose when a 2 * 2 cm(2) field was used. Testing of the
      algorithms using the anthropomorphic phantom showed that the maximum
      overestimation by the PBC algorithm was 20.7%, while that by the AAA was 8.3%.
      When multiple fields were used in a patient geometry, the dose prediction errors
      of the AAA would be substantially reduced compared with those from a single
      field. However, overestimation of more than 3% could still be found at some
      points at the air-tissue interface.

PMID- 21178237
TI  - Dose conversion coefficients for photon exposure of the human eye lens.
AB  - In recent years, several papers dealing with the eye lens dose have been
      published, because epidemiological studies implied that the induction of
      cataracts occurs even at eye lens doses of less than 500 mGy. Different questions
      were addressed: Which personal dose equivalent quantity is appropriate for
      monitoring the dose to the eye lens? Is a new definition of the dose quantity
      H(p)(3) based on a cylinder phantom to represent the human head necessary? Are
      current conversion coefficients from fluence to equivalent dose to the lens
      sufficiently accurate? To investigate the latter question, a realistic model of
      the eye including the inner structure of the lens was developed. Using this eye
      model, conversion coefficients for electrons have already been presented. In this
      paper, the same eye model-with the addition of the whole body-was used to
      calculate conversion coefficients from fluence (and air kerma) to equivalent dose
      to the lens for photon radiation from 5 keV to 10 MeV. Compared to the values
      adopted in 1996 by the International Commission on Radiological Protection
      (ICRP), the new values are similar between 40 keV and 1 MeV and lower by up to a
      factor of 5 and 7 for photon energies at about 10 keV and 10 MeV, respectively.
      Above 1 MeV, the new values (calculated without kerma approximation) should be
      applied in pure photon radiation fields, while the values adopted by the ICRP in
      1996 (calculated with kerma approximation) should be applied in case a
      significant contribution from secondary electrons originating outside the body is
      present.

PMID- 21178239
TI  - Novel methodology to characterize electromagnetic exposure of the brain.
AB  - Due to the greatly non-uniform field distribution induced in brain tissues by
      radio frequency electromagnetic sources, the exposure of anatomical and
      functional regions of the brain may be a key issue in interpreting laboratory
      findings and epidemiological studies concerning endpoints related to the central
      nervous system. This paper introduces the Talairach atlas in characterization of
      the electromagnetic exposure of the brain. A hierarchical labeling scheme is
      mapped onto high-resolution human models. This procedure is fully automatic and
      allows identification of over a thousand different sites all over the brain. The
      electromagnetic absorption can then be extracted and interpreted in every region
      or combination of regions in the brain, depending on the characterization goals.
      The application examples show how this methodology enhances the dosimetry
      assessment of the brain based on results obtained by either finite difference
      time domain simulations or measurements delivered by test compliance dosimetry
      systems. Applications include, among others, the detailed dosimetric analysis of
      the exposure of the brain during cell phone use, improved design of exposure
      setups for human studies or medical diagnostic and therapeutic devices using
      electromagnetic fields or ultrasound.

PMID- 21178238
TI  - Monte Carlo estimation of radiation doses during paediatric barium meal and
      cystourethrography examinations.
AB  - Organ doses are important quantities in assessing the radiation risk. In the case
      of children, estimation of this risk is of particular concern due to their
      significant radiosensitivity and the greater health detriment. The purpose of
      this study is to estimate the organ doses to paediatric patients undergoing
      barium meal and micturating cystourethrography examinations by clinical
      measurements and Monte Carlo simulation. In clinical measurements, dose-area
      products (DAPs) were assessed during examination of 50 patients undergoing barium
      meal and 90 patients undergoing cystourethrography examinations, separated
      equally within three age categories: namely newborn, 1 year and 5 years old.
      Monte Carlo simulation of photon transport in male and female mathematical
      phantoms was applied using the MCNP5 code in order to estimate the equivalent
      organ doses. Regarding the micturating cystourethrography examinations, the
      organs receiving considerable amounts of radiation doses were the urinary bladder
      (1.87, 2.43 and 4.7 mSv, the first, second and third value in the parentheses
      corresponds to neonatal, 1 year old and 5 year old patients, respectively), the
      large intestines (1.54, 1.8, 3.1 mSv), the small intestines (1.34, 1.56, 2.78
      mSv), the stomach (1.46, 1.02, 2.01 mSv) and the gall bladder (1.46, 1.66, 2.18
      mSv), depending upon the age of the child. Organs receiving considerable amounts
      of radiation during barium meal examinations were the stomach (9.81, 9.92, 11.5
      mSv), the gall bladder (3.05, 5.74, 7.15 mSv), the rib bones (9.82, 10.1, 11.1
      mSv) and the pancreas (5.8, 5.93, 6.65 mSv), depending upon the age of the child.
      DAPs to organ/effective doses conversion factors were derived for each age and
      examination in order to be compared with other studies.

PMID- 21178240
TI  - Leakage of the Siemens 160 MLC multileaf collimator on a dual energy linear
      accelerator.
AB  - Multileaf collimators (MLCs) have been in clinical use for many years and
      meanwhile are commonly used to deliver intensity-modulated radiotherapy (IMRT)
      beams. For this purpose it is important to know their dosimetric properties
      precisely, one of them being inter- and intraleaf leakage. The Siemens 160 MLC
      features a single focus design with flat-sided and tilted leaves instead of
      tongue-and-groove. The leakage performance of the 160 MLC was investigated on a
      dual energy linear accelerator Siemens ARTISTE with 6 MV and 18 MV photon
      energies. While the intraleaf leakage amounted to nearly the same dose for 6 and
      for 18 MV, a much higher interleaf leakage for 6 MV was measured. It could be
      reduced by simply rotating the collimator, and also by changing the voltage
      applied to the beam steering coils. The leakage of the 160 MLC is shown to be
      sensitive to beam alignment. This is of special interest for dual energy
      accelerators, as the two focal spots of both energies, neither in position nor in
      shape, do not necessarily always coincide. As a consequence of that, a higher
      leakage can be expected for one out of two energies for the 160 MLC.

PMID- 21178241
TI  - Modelling intercellular communication and its effects on tumour invasion.
AB  - We present a model aiming at the description of intercellular communication on
      the invasive character of gliomas. We start from a previous model of ours based
      on a cellular automaton and develop a new version of it in a three-dimensional
      geometry. Introducing the hydrodynamic limit of the automaton we obtain a
      macroscopic model involving a nonlinear diffusion equation. We show that this
      macroscopic model is quite adequate for the description of realistic situations.
      Comparison of the simulations with experimental results shows agreement with the
      finding that the inhibition of intercellular communication (through gap
      junctions) tends to decrease migration. As an application of our model we
      estimated the possible increase in life expectancy, due to reduced cell migration
      mediated by the inhibition of intercellular communication, on patients suffering
      from gliomas. We find that the obtained increase may amount to a 20% gain in the
      case of unresectable tumours.

PMID- 21178242
TI  - Probing GFP-actin diffusion in living cells using fluorescence correlation
      spectroscopy.
AB  - The cytoskeleton of eukaryotic cells is continuously remodeled by polymerization
      and depolymerization of actin. Consequently, the relative content of polymerized
      filamentous actin (F-actin) and monomeric globular actin (G-actin) is subject to
      temporal and spatial fluctuations. Since fluorescence correlation spectroscopy
      (FCS) can measure the diffusion of fluorescently labeled actin it seems likely
      that FCS allows us to determine the dynamics and hence indirectly the structural
      properties of the cytoskeleton components with high spatial resolution. To this
      end we investigate the FCS signal of GFP-actin in living Dictyostelium discoideum
      cells and explore the inherent spatial and temporal signatures of the actin
      cytoskeleton. Using the free green fluorescent protein (GFP) as a reference, we
      find that actin diffusion inside cells is dominated by G-actin and slower than
      diffusion in diluted cell extract. The FCS signal in the dense cortical F-actin
      network near the cell membrane is probed using the cytoskeleton protein LIM and
      is found to be slower than cytosolic G-actin diffusion. Furthermore, we show that
      polymerization of the cytoskeleton induced by Jasplakinolide leads to a
      substantial decrease of G-actin diffusion. Pronounced fluctuations in the
      distribution of the FCS correlation curves can be induced by latrunculin, which
      is known to induce actin waves. Our work suggests that the FCS signal of GFP
      actin in combination with scanning or spatial correlation techniques yield
      valuable information about the local dynamics and concomitant cytoskeletal
      properties.

PMID- 21178243
TI  - Singularity analysis of the AKT signaling pathway reveals connections between
      cancer and metabolic diseases.
AB  - Connections between cancer and metabolic diseases may consist in the complex
      network of interactions among a common set of biomolecules. By applying
      singularity and bifurcation analysis, the phenotypes constrained by the AKT
      signaling pathway are identified and mapped onto the parameter space, which
      include cancer and certain metabolic diseases. By considering physiologic
      properties (sensitivity, robustness and adaptivity) the AKT pathway must possess
      in order to efficiently sense growth factors and nutrients, the region of normal
      responses is located. To optimize these properties, the intracellular
      concentration of the AKT protein must be sufficiently high to saturate its
      enzymes; the strength of the positive feedback must be stronger than that of the
      negative feedback. The analysis illuminates the parameter space and reveals
      system-level mechanisms in regulating biological functions (cell growth,
      survival, proliferation and metabolism) and how their deregulation may lead to
      the development of diseases. The analytical expressions summarize the synergistic
      interactions among many molecules, which provides valuable insights into
      therapeutic interventions. In particular, a strategy for overcoming the
      limitations of mTOR inhibition is proposed for cancer therapy.

PMID- 21178244
TI  - Can the PHS model (ISO7933) predict reasonable thermophysiological responses
      while wearing protective clothing in hot environments?
AB  - In this paper, the prediction accuracy of the PHS (predicted heat strain) model
      on human physiological responses while wearing protective clothing ensembles was
      examined. Six human subjects (aged 29 +/- 3 years) underwent three experimental
      trials in three different protective garments (clothing thermal insulation I(cl)
      ranges from 0.63 to 2.01 clo) in two hot environments (40  degrees C, relative
      humidities: 30% and 45%). The observed and predicted mean skin temperature, core
      body temperature and sweat rate were presented and statistically compared. A
      significant difference was found in the metabolic rate between FIRE (firefighting
      clothing) and HV (high visibility clothing) or MIL (military clothing) (p <
      0.001). Also, the development of heart rate demonstrated the significant effects
      of the exposure time and clothing ensembles. In addition, the predicted
      evaporation rate during HV, MIL and FIRE was much lower than the experimental
      values. Hence, the current PHS model is not applicable for protective clothing
      with intrinsic thermal insulations above 1.0 clo. The results showed that the PHS
      model generated unreliable predictions on body core temperature when human
      subjects wore thick protective clothing such as firefighting clothing (I(cl) >
      1.0 clo). The predicted mean skin temperatures in three clothing ensembles HV,
      MIL and FIRE were also outside the expected limits. Thus, there is a need for
      further extension for the clothing insulation validation range of the PHS model.
      It is recommended that the PHS model should be amended and validated by
      individual algorithms, physical or physiological parameters, and further subject
      studies.

PMID- 21178245
TI  - Pitot-tube flowmeter for quantification of airflow during sleep.
AB  - The gold-standard pneumotachograph is not routinely used to quantify airflow
      during overnight polysomnography due to the size, weight, bulkiness and
      discomfort of the equipment that must be worn. To overcome these deficiencies
      that have precluded the use of a pneumotachograph in routine sleep studies, our
      group developed a lightweight, low dead space 'pitot flowmeter' (based on pitot
      tube principle) for use during sleep. We aimed to examine the characteristics and
      validate the flowmeter for quantifying airflow and detecting hypopneas during
      polysomnography by performing a head-to-head comparison with a pneumotachograph.
      Four experimental paradigms were utilized to determine the technical performance
      characteristics and the clinical usefulness of the pitot flowmeter in a head-to
      head comparison with a pneumotachograph. In each study (1-4), the pitot flowmeter
      was connected in series with a pneumotachograph under either static flow (flow
      generator inline or on a face model) or dynamic flow (subject breathing via a
      polyester face model or on a nasal mask) conditions. The technical
      characteristics of the pitot flowmeter showed that, (1) the airflow resistance
      ranged from 0.065 +/- 0.002 to 0.279 +/- 0.004 cm H(2)O L(-1) s(-1) over the
      airflow rates of 10 to 50 L min(-1). (2) On the polyester face model there was a
      linear relationship between airflow as measured by the pitot flowmeter output
      voltage and the calibrated pneumotachograph signal a (beta(1) = 1.08 V L(-1) s(
      1); beta(0) = 2.45 V). The clinically relevant performance characteristics
      (hypopnea detection) showed that (3) when the pitot flowmeter was connected via a
      mask to the human face model, both the sensitivity and specificity for detecting
      a 50% decrease in peak-to-peak airflow amplitude was 99.2%. When tested in
      sleeping human subjects, (4) the pitot flowmeter signal displayed 94.5%
      sensitivity and 91.5% specificity for the detection of 50% peak-to-peak
      reductions in pneumotachograph-measured airflow. Our data validate the pitot
      flowmeter for quantification of airflow and detecting breathing reduction during
      polysomnographic sleep studies. We speculate that quantifying airflow during
      sleep can differentiate phenotypic traits related to sleep disordered breathing.

PMID- 21178246
TI  - Chest tcpO2 changes during constant-load treadmill walking tests in patients with
      claudication.
AB  - Changes in chest transcutaneous-pO(2) at rest (DeltatcpO(2)) mimic absolute
      changes in arterial-pO(2) during moderate exercise, although the absolute
      starting values may dramatically differ. We retrospectively studied 485 patients
      (group 1), prospectively studied 292 new patients (group 2) and estimated the
      intra-test and the test-retest reproducibility of DeltatcpO(2) during constant
      load treadmill tests: 3.2 km h(-1), 10% grade, using the cross correlation
      technique. Patients were classified into groups according to their best fit to
      nine pre-defined mathematic models. Respectively, 71% and 76% of patients of
      groups 1 and 2 fitted with a model showing a DeltatcpO(2) increase during and a
      decrease following exercise. Another 18% and 12% of the patients of groups 1 and
      2 respectively fitted with a model that showed an abrupt decrease at exercise
      onset, a slow increase during walking and an overshoot in the recovery period,
      referred here as a walking-induced transcutaneous hack (WITH) profile. The mean
      r(max) value for the cross-correlation analysis was 0.919 +/- 0.091 and 0.800 +/-
      0.129 for intra-test and test-retest reproducibility. Most profiles show the
      expected DeltatcpO(2) exercise-induced increase. Future studies are needed to
      confirm and explain the WITH profiles that we found, and screen for potential
      associated diseases.

PMID- 21178247
TI  - Comparison of different threshold values r for approximate entropy: application
      to investigate the heart rate variability between heart failure and healthy
      control groups.
AB  - Approximate entropy (ApEn) is widely accepted as a complexity measure of the
      heart rate variability (HRV) signal, but selecting the criteria for the threshold
      value r is controversial. This paper aims to verify whether Chon's method of
      forecasting the r(max) is an appropriate one for the HRV signal. The standard
      limb lead ECG signals of 120 subjects were recorded for 10 min in a supine
      position. The subjects were divided into two groups: the heart failure (22
      females and 38 males, median age 62.4 +/- 12.6) and healthy control group (33
      females and 27 males, median age 51.5 +/- 16.9). Three types of ApEn were
      calculated: the ApEn(0.2) using the recommended constant r = 0.2, the ApEn(chon)
      using Chon's method and the ApEn(max) using the true r(max). A Wilcoxon rank sum
      test showed that the ApEn(0.2) (p = 0.267) and the ApEn(max) (p = 0.813) had no
      statistical differences between the two groups, while the ApEn(chon) (p = 0.040)
      had. We generated a synthetic database to study the effect of two influential
      factors (the signal length N and the ratio of short- and long-term variability
      sd(1)/sd(2)) on the empirical formula in Chon's method (Chon et al 2009 IEEE Eng.
      Med. Biol. Mag. 28 18-23). The results showed that the empirical formula proposed
      by Chon et al is a good method for analyzing the random signal, but not an
      appropriate tool for analyzing nonlinear signals, such as the logistic or HRV
      signals.

PMID- 21178248
TI  - Design and implementation of a novel superfusion system for ex vivo
      characterization of neural tissue by dielectric spectroscopy (DS).
AB  - Dielectric spectroscopy is a widely utilized electrophysiological
      characterization method. The obtained dielectric spectra and derived properties
      have the potential of providing significant information regarding changes in the
      physiological state of a biological system. However, since many of the dielectric
      properties are obtained in vitro from excised tissue far removed from
      physiological conditions, the value of the information obtained may be
      diminished. In this paper, we introduce a superfusion system that is designed to
      produce ex vivo dielectric spectroscopy measurements by providing the living
      tissue with a continuous and ample supply of nutrients and oxygen while removing
      metabolites and other waste. This superfusion system provides the convenience of
      in vitro measurement while concurrently producing results that can be more
      closely correlated with actual physiological changes in the biological system.

PMID- 21178249
TI  - Short-term memory and electrical restitution in the canine transmural ventricle.
AB  - Cardiac short-term memory is an intrinsic property of paced myocardium that
      reflects the influence of pacing history. Using an optical mapping method to
      record membrane voltage and intracellular calcium (Ca(2 +)(i)), this study
      investigated the properties and mechanisms of short-term memory in isolated and
      perfused canine wedge preparations. In addition to the dynamic and S1S2 pacing
      protocols, a perturbed downsweep pacing protocol was used to get a complete
      overview of the restitution portrait. Abrupt changes in basic cycle length (BCL)
      were applied to investigate the accommodation process of action potential
      duration (APD). The results showed unobvious differences of memory among the epi
      , mid- and endo-myocytes, implying an insignificant memory-induced transient
      heterogeneity in APD across the transmural canine hearts. With the decrease of
      pacing rate S1, memory gradually elevated and achieved a maximum around 400 ms,
      and then reduced as S1 decreased further, indicating a non-monotonic relationship
      between memory and the pacing rate. After suppressing the Ca(2 +)(i) transient
      with ryanodine (3 umol l(-1)), the accommodation process of APD to a new BCL
      significantly abbreviated (tau = 37.41 +/- 4.42 stimuli before ryanodine, tau =
      15.84 +/- 4.74 stimuli after ryanodine, p < 0.01). Therefore, Ca(2 +)(i) cycling
      was suggested to play an important role in memory during dynamic pacing.

PMID- 21178250
TI  - In vivo quantification of accumulating abdominal fluid using an electrical
      impedance tomography hemiarray.
AB  - A new method to image and quantify intra-abdominal haemorrhage using electrical
      impedance tomography (EIT) was tested in vivo. Supine peritoneal dialysis
      patients were monitored using an 8-electrode hemiarray placed on the anterior
      abdomen. EIT measurements were recorded using the EPack II data acquisition
      system before, during, and after the administration of dialysate. The amount of
      dialysate infused was recorded synchronous with EIT measurements and used as a
      control. Tomographic images of impedance change were reconstructed using a
      weighted, sensitivity-based method and then post-processed to obtain a
      quantitative estimate of the total dialysate volume added and the rate of
      dialysate administration. Our preliminary study included two subjects, one male
      and one female, each of whom participated for two sessions spaced about 6 months
      apart. Data collected from these sessions indicated that with an in vivo SNR of
      about 35 dB the EPack II can detect accumulations larger than about 100 ml, with
      a quantification uncertainty of about 50 ml. The rate of accumulation was
      determined in less than 2 min. This method shows promise for automated detection
      of other pathologies, eg ascites, and is adaptable to detecting conductive
      accumulations in other anatomy.

PMID- 21178251
TI  - Mechanism of fine ripple formation on surfaces of (semi)transparent materials via
      a half-wavelength cavity feedback.
AB  - The mechanism of the fine ripples, perpendicular to laser polarization, on the
      surface of (semi)transparent materials with period smaller than the vacuum
      wavelength, lambda, of the incident radiation is proposed and experimentally
      validated. The sphere-to-plane transformation of nanoplasma bubbles responsible
      for the in-bulk ripples accounts for the fine ripples on the surface of
      dielectrics and semiconductors. The mechanism is demonstrated for 4H:SiC and
      sapphire surfaces using 800 nm/150 fs and 1030 nm/300 fs laser pulses. The
      ripples are pinned to the smallest possible standing wave cavity inside material
      of refractive index n. This defines the corresponding period, Lambda =
      (lambda/n)/2, of a light standing wave with intensity, E(2), at the maxima of
      which surface ablation occurs. The mechanism accounts for the fine ripples at the
      breakdown conditions. Comparison with ripples recorded on different materials and
      via other mechanisms using femtosecond pulses is presented and application
      potential is discussed.

PMID- 21178252
TI  - Synthesis and magnetic characterization of MnAs nanoparticles via nanoparticle
      conversion.
AB  - We report on the synthesis of ferromagnetic manganese arsenide (MnAs)
      nanoparticles via the conversion of primary Mn particles which are generated in
      an aerosol process in a spark discharge generator. After sintering and size
      selection in an aerosol setup, the particles are deposited on GaAs(100)B and
      Si(111) substrates. Subsequent conversion to MnAs particles takes place in an
      annealing process under a hydrogen atmosphere with an arsine background pressure.
      The magnetic properties are studied using a SQUID magnetometer. The annealed MnAs
      particles exhibit hexagonal facets and show anisotropic magnetic behaviour on
      GaAs(100)B substrates, whereas on Si(111) they remain spherical and show
      isotropic magnetic behaviour. Scanning transmission electron microscopy studies
      are used to confirm the conversion from Mn to MnAs.

PMID- 21178253
TI  - Scalable network electrical devices using ZnO nanowalls.
AB  - We report the fabrication and electrical characteristics of scalable nanowall
      network devices and their gas sensor applications. For the network device
      fabrications, two-dimensional ZnO nanowall networks were grown on AlN/Si
      substrates with a patterned SiO(2) mask layer using selective-area metal-organic
      vapor-phase epitaxy. The ZnO nanowalls with c-axis orientation were
      heteroepitaxially grown on AlN/Si substrates, and were single-crystalline, as
      determined by x-ray diffraction and transmission electron microscopy. The
      electrical conductivity of the nanowall networks was measured as a function of
      nanowall dimensions. The conductance increased linearly with the channel width
      for widths larger than 1 um, but saturated at 36 uS for widths below 1 um. This
      conductance scaling behavior is explained by enhanced conduction through the
      regions near the edge of the patterned growth areas, where the density of the
      networks was higher. Gas sensor applications were investigated using the nanowall
      network devices, and highly sensitive gas detection was demonstrated.

PMID- 21178255
TI  - An ordered Si nanowire with NiSi2 tip arrays as excellent field emitters.
AB  - A method was developed to grow ordered silicon nanowire with NiSi(2) tip arrays
      by reacting nickel thin films on silica-coated ordered Si nanowire (NW) arrays.
      The coating of thin silica shell on Si NW arrays has the effect of limiting the
      diffusion of nickel during the silicidation process to achieve the single
      crystalline NiSi(2) NWs. In the meantime, it relieves the distortion of the NWs
      caused by the strain associated with formation of NiSi(2) to maintain the
      straightness of the nanowire and the ordering of the arrays. Other nickel
      silicide phases such as Ni(2)Si and NiSi were obtained if the silicidation
      processes were conducted on the ordered Si NWs without a thin silica shell.
      Excellent field emission properties were found for NiSi(2)/Si NW arrays with a
      turn on field of 0.82 V um(-1) and a threshold field of 1.39 V um(-1). The field
      enhancement factor was calculated to be about 2440. The stability test showed a
      fluctuation of about 7% with an applied field of 2.6 V um(-1) for a period of 24
      h. The excellent field emission characteristics are attributed to the well
      aligned and highly ordered arrangement of the single crystalline NiSi(2)/Si
      heterostructure field emitters. In contrast to other growth methods, the present
      growth of ordered nickel silicide/Si NWs on silicon is compatible with silicon
      nanoelectronics device processes, and also provides a facile route to grow other
      well-aligned metal silicide NW arrays. The advantages will facilitate its
      applications as field emission devices.

PMID- 21178254
TI  - Microwave assisted nanoparticle surface functionalization.
AB  - We introduce the input of microwave energy to elaborate a multimodal magnetic
      nanoplatform. This magnetic nanomaterial consists of superparamagnetic
      gammaFe(2)O(3) nanoparticles conjugated to hydroxymethylene bisphosphonate (HMBP)
      molecules with an amine function as the terminal group. The feasibility of such a
      process is illustrated by the coupling of Rhodamine B to the hybrid magnetic
      nanomaterial. Using a microwave we manage to have approximately a 50 fold
      increase in molecules per nanoparticle compared to conventional procedures.
      Moreover we show that the amount of Rhodamine on the nanoparticle surface could
      be tuned using various stoichiometric ratios. The presence of Rhodamine B on the
      nanoparticle surface provides an amphiphilic character to facilitate penetration
      into the cells.

PMID- 21178256
TI  - Temperature-dependent phase transitions in zeptoliter volumes of a complex
      biological membrane.
AB  - Phase transitions in purple membrane have been a topic of debate for the past two
      decades. In this work we present studies of a reversible transition of purple
      membrane in the 50-60  degrees C range in zeptoliter volumes under different
      heating regimes (global heating and local heating). The temperature of the
      reversible phase transition is 52 +/- 5  degrees C for both local and global
      heating, supporting the hypothesis that this transition is mainly due to a
      structural rearrangement of bR molecules and trimers. To achieve high resolution
      measurements of temperature-dependent phase transitions, a new scanning probe
      microscopy-based method was developed. We believe that our new technique can be
      extended to other biological systems and can contribute to the understanding of
      inhomogeneous phase transitions in complex systems.

PMID- 21178257
TI  - A carbon-nanotube-based sensor array for formaldehyde detection.
AB  - We have fabricated a sensor array consisting of 32 sensor elements with pristine,
      doped and metal-loaded single-wall carbon nanotubes as sensing materials. The
      sensor elements consist of interdigitated electrodes with varying finger widths
      and gaps. The chemiresistor-type sensors provide a significant response to
      formaldehyde at concentrations down to 10 ppb in air with rapid response and
      recovery times.

PMID- 21178258
TI  - Hydrogen sensing properties of protective-layer-coated single-walled carbon
      nanotubes with palladium nanoparticle decoration.
AB  - Protective-layer-coated single-walled carbon nanotubes (SWNTs) with palladium
      nanoparticle decoration (Pd-SiO(2)-SWNTs) were fabricated and their sensing
      properties for hydrogen (H(2)) were investigated. SWNTs were coated with a 3-4 nm
      thick SiO(2) layer by pulsed laser deposition and subsequently decorated with Pd
      nanoparticles by electron beam evaporation. Even though the SWNTs were completely
      surrounded by a protective layer, Pd-SiO(2)-SWNTs responded to H(2) down to a
      concentration of 1 part per million. Compared with the Pd nanoparticle-decorated
      SWNTs without a protective layer (Pd-SWNTs), Pd-SiO(2)-SWNTs exhibited highly
      stable sensor responses with variations of less than 20%; Pd-SWNTs showed a
      variation of 80%. The density of the Pd-SWNTs significantly decreased after the
      sensing test, while that of the Pd-SiO(2)-SWNTs with the netlike structure
      remained unchanged. The hydrogen sensing mechanism of the Pd-SiO(2)-SWNTs was
      attributed to the chemical gating effect on the SWNTs due to dipole layer
      formation by hydrogen atoms trapped at the Pd-SiO(2) interface. Moreover, the
      relationship between H(2) concentration and sensor response can be described by
      the Langmuir isotherm for dissociative adsorption.

PMID- 21178259
TI  - Electron beam induced deposition at elevated temperatures: compositional changes
      and purity improvement.
AB  - Thermally assisted electron beam induced deposition can result in an improvement
      of the purity of nano-scale depositions. Six commonly used organic precursors
      were examined: W(CO)(6), TEOS (tetraethylorthosilicate), MeCpPtMe(3),
      Co(CO)(3)NO, Co(2)(CO)(8), and Me(2)Auacac. The last two precursors were also
      tested on two different instruments to confirm reproducibility of the results.
      The influence of the substrate temperature on the composition of the deposition
      has been quantified systematically in the temperature range 25-360  degrees C. It
      has been shown that most purities improve when applying an elevated temperature,
      while the shape of the deposition remains intact. The purity improvement is
      achieved at the cost of a lower deposition yield. The amount of improvement is
      different for each precursor. Within the maximum temperature range of 360 
      degrees C, the best improvement was found for W(CO)(6): from 36.7 at.% at 25 
      degrees C to 59.2 at.% at 280  degrees C. For both cobalt precursors an
      additional transition region between patterned electron beam induced deposition
      (EBID) and thermal thin film growth has been identified. In this region seeded
      growth occurs with strongly increased growth rates.

PMID- 21178260
TI  - Modeling of epitaxial graphene functionalization.
AB  - A new model for graphene epitaxially grown on silicon carbide is proposed.
      Density functional theory modeling of epitaxial graphene functionalization by
      hydrogen, fluorine, methyl and phenyl groups has been performed, with hydrogen
      and fluorine showing a high probability of cluster formation in high adatom
      concentration. It has also been shown that the clusterization of fluorine adatoms
      provides midgap states in formation, due to significant flat distortion of
      graphene. The functionalization of epitaxial graphene using larger species
      (methyl and phenyl groups) renders cluster formation impossible, due to the
      steric effect, and results in uniform coverage with the energy gap opening.

PMID- 21178261
TI  - Nanostructuring discotic molecules on ITO support.
AB  - Patterning of organic compounds on a nanometer length scale is of great interest
      for solar applications: defined control over the donor-acceptor interface will
      allow design of an optimized nano-morphology promoting exciton separation and
      reducing charge recombination. Herein we present an imprinting technique using
      anodized alumina oxide (AAO) hard templates as stamps. We show an exact pattern
      transfer of the AAO structures into a solution processable hexa-peri
      hexabenzocoronene (HBC), a discotic small molecule with acrylate moieties which
      is polymerized in situ. Film fabrication is realized for a variety of nanowire
      dimensions on square centimeter areas. The fabrication directly on conductive
      glass support and control over the formation of a dense barrier layer render this
      approach appealing for the fabrication of fully organic nanostructured
      photovoltaic devices.

PMID- 21178262
TI  - Integrated metabonomics analysis of the size-response relationship of silica
      nanoparticles-induced toxicity in mice.
AB  - Understanding the underlying properties-dependent interactions of nanostructures
      with biological systems is essential to nanotoxicological research. This study
      investigates the relationship between particle size and toxicity, and further
      reveals the mechanism of injury, using silica particles (SP) with diameters of
      30, 70, and 300 nm (SP30, SP70, and SP300) as model materials. The biochemical
      compositions of liver tissues and serum of mice treated with SP30, SP70, and
      SP300 were analyzed by integrated metabonomics analysis based on gas
      chromatography-mass spectrometry (GC-MS) and in combination with pattern
      recognition approaches. Histopathological examinations and serum biochemical
      analysis were simultaneously performed. The toxicity induced by three different
      sizes of SP mainly involved hepatocytic necrosis, increased serum
      aminotransferase, and inflammatory cytokines. Moreover, the toxic effects of SP
      were dose-dependent for each particle size. The doses of SP30, SP70, and SP300
      that were toxic to the liver were 10, 40, and 200 mg kg(-1), respectively. In
      this study, surface area has a greater effect than particle number on the
      toxicity of SP30, SP70, and SP300 in the liver. The disturbances in energy
      metabolism, amino acid metabolism, lipid metabolism, and nucleotide metabolism
      may be attributable to the hepatotoxicity induced by SP. In addition, no major
      differences were found in the response of biological systems caused by the
      different SP sizes among the metabolite profiles. The results suggest that not
      only nano-sized but also submicro-sized SP can cause similar extents of liver
      injury, which is dependent on the exposure dose, and the mechanism of toxicity
      may be almost the same.

PMID- 21178263
TI  - SWNT array resonant gate MOS transistor.
AB  - We show that thin horizontal arrays of single wall carbon nanotubes (SWNTs)
      suspended above the channel of silicon MOSFETs can be used as vibrating gate
      electrodes. This new class of nano-electromechanical system (NEMS) combines the
      unique mechanical and electronic properties of SWNTs with an integrated silicon
      based motion detection. Its electrical response exhibits a clear signature of the
      mechanical resonance of SWNT arrays (120-150 MHz) showing that these thin
      horizontal arrays behave as a cohesive, rigid and elastic body membrane with a
      Young's modulus in the order of 1-10 GPa and ultra-low mass. The resonant
      frequency can be tuned by the gate voltage and its dependence is well understood
      within the continuum mechanics framework.

PMID- 21178264
TI  - Serum thymidine kinase 1 activity in breast cancer.
AB  - AIMS: Thymidine kinase 1 (TK1) is an enzyme involved in DNA synthesis and an
      important proliferation marker. We explored the association of preoperative serum
      TK1 activity with clinicopathological parameters and prognosis in terms of
      recurrence-free survival (RFS) in breast cancer (BC) patients. PATIENTS AND
      METHODS: TK1 activity in serum of 120 healthy women and 161 BC patients was
      measured by quantitative ELISA. RESULTS: Serum TK1 activity in BC patients was
      significantly higher than in healthy women (P < 0.0001). In BC patients elevated
      TK1 activity was significantly associated with advanced T stage (P = 0.015),
      higher grade (P = 0.013), presence of tumor necrosis (P = 0.006), vascular
      invasion (P = 0.002), and lack of estrogen receptor (ER) and progesterone
      receptor (PR) expression (P = 0.0004 and P = 0.003). Higher TK1 activity was
      found in patients with BRCA1/2 mutations compared to those without the mutation
      (P = 0.004). Multivariate Cox proportional hazards analyses demonstrated that
      TK1, adjusted for stage, grade, necrosis, ER and PR negativity was retained as an
      independent predictor of disease recurrence (Hazard Ratio = 3.9, 95%CI 1.3-11.6,
      P = 0.013). CONCLUSION: Elevated serum TK1 is an important risk factor indicating
      a high proliferation potential of tumors at the time of excision. In multivariate
      analysis TK1 activity was found to be an independent prognostic factor for RFS.

PMID- 21178265
TI  - WT1 expression in normal and neoplastic cranial and peripheral nerves is
      independent of grade of malignancy.
AB  - OBJECTIVE: Wilms' tumor protein (WT1) expression is usually absent in normal
      glial cells of the CNS but is highly upregulated in brain tumor cells and its
      expression correlates with tumor grade. However, knowledge on WT1 expression in
      tumors of the peripheral nerve system (PNS) is limited. As WT1 antibodies not
      only serve as biomarker for cancerous tissue but also are considered for cancer
      immunotherapy, knowledge of WT1 expression in tumorous and normal peripheral
      nerve tissue is important for therapeutical purposes. METHODS: We analyze the
      immunohistochemical expression of WT1 in 101 samples consisting of 13 normal
      nerves, 10 neurofibromas, 69 schwannomas and 9 malignant peripheral nerve sheath
      tumors (MPNST). Tumor samples included 14 specimen from patients with a proven
      neurocutaneous disorder (neurofibromatosis type 1 and 2) and 3 cases of
      schwannomatosis. In 50 vestibular schwannomas tumor growth extension was
      correlated to WT1 expression. RESULTS: WT1 expression is present in Schwann cells
      of the majority of normal human nerves (11/13). In peripheral nerve sheath
      tumors, cytoplasmic WT1 protein is expressed in the cytoplasm of the neoplastic
      cells in all tumors, including MPNST, neurofibromas and schwannomas. The WT1
      expression is independent of tumor malignancy or tumor growth extension and is
      not associated with a neurocutaneous disorder. CONCLUSION: WT1 expression in
      normal and neoplastic tissue differs in the peripheral and the central nervous
      system. These findings may point to a different functional role of WT1 in the PNS
      and the CNS.

PMID- 21178266
TI  - Formation of AR-SMRT binding in prostate cancer cells treated with natural
      histone deacetylase inhibitor.
AB  - Signaling through the androgen receptor (AR) plays a critical role in prostate
      cancer progression. The AR is a classical nuclear receptor (NR) providing a link
      between signaling molecule and transcription response. Histone deacetylase
      inhibitors (HDACI) have antiproliferative and proapoptotic effects on prostate
      cancer cells and their implication in silence AR signaling may have potential
      therapeutic use. We aimed to study the inhibitory effects of the corepressor SMRT
      (Silencing Mediator for Retinoid and Thyroid hormone receptors) which forms a
      complex together with nuclear receptor corepressor (N-CoR) and with histone
      deacetylase 3 (HDAC3) on AR activity. The androgen-sensitive prostate cancer cell
      line LNCaP and androgen-insensitive prostate cancer cell line C4-2 both AR
      positive, and androgen-insensitive DU145 and PC3 prostate cancer cell lines were
      treated with two HDACIs, sodium butyrate (NaB) and/or trichostatin A (TSA). We
      amplified immunoprecipitated DNA by conventional PCR and in the following step we
      used the chromatin immunoprecipitation (ChIP) analysis coupled with quantitative
      PCR for monitoring NaB induced formation of AR-SMRT/N-CoR complex binding on the
      PSA promoter. The co-immunoprecipitation assay revealed increase in AR-SMRT
      formation in NaB treated cells. Simultaneously, the Western blot analysis showed
      a significant decrease in AR protein expression. Furthermore, we estimated the
      reduced presence of HDAC2 and HDAC3 proteins by NaB and TSA treatment in AR
      negative DU145 cell line. In conclusion, the inhibitory effect of NaB on AR gene
      expression seems to be specific and unique for prostate cancer AR-positive cell
      lines and corresponds with its ability to stimulate AR-SMRT complex formation. We
      suggest that AR and SMRT/N-CoR corepressors may form a stable complex in vitro
      and NaB may facilitate the interaction between AR nuclear steroid receptor and
      SMRT corepressor protein.

PMID- 21178267
TI  - Correlation of altered blood albumin characteristics and lymphocyte populations
      to tumor stage in gastrointestinal cancer patients.
AB  - The fluorescent probe ABM was used to characterize lymphocyte membranes and blood
      plasma albumin from cancer patients suffering from colorectal cancer or gastric
      cancers at Stages II-IV. The aim of these studies was to evaluate the potential
      utility of measures of ABM fluorescence intensity as a standard tool in the
      analyses of host immune status and for a clinical interpretation of alterations
      in albumin per se and lymphocyte functional activity in cancer patients. The
      fluorescence intensity of ABM in the blood plasma decreased from control values
      and showed specific differences in each of the differing patients groups; these
      changes corresponded to cancer stage. The significant decrease in ABM
      fluorescence in the plasma could be explained, in part, by a diminished binding
      capacity of the albumin of these patients. The lymphocyte distribution among the
      subsets of patients also differed. Interestingly, the ABM fluorescence in the
      cell suspension and blood plasma was also found to correlate with select
      immunological parameters (CD4(+):CD8(+) ratios, lymphocyte counts, etc.) in the
      patients. These results obtained here showed that there was a strong agreement
      between changes in ABM spectral characteristics and both clinical and
      pathological estimates of disease (i.e., gastrointestinal cancers) severity.
      Thus, the use of ABM spectroscopy appears to be another tool that might be of
      some used by clinicians to monitor the course of certain diseases, such as
      gastrointestinal cancers.

PMID- 21178268
TI  - Exploratory study of a KLK2 polymorphism as a prognostic marker in prostate
      cancer.
AB  - OBJECTIVES: An association of a single nucleotide polymorphism (SNP) of the KLK2
      gene (rs198977; c.748C>T; R250W) with risk for developing prostate cancer has
      been observed. We evaluated the role of R250W SNP for prognosis in prostate
      cancer. METHODS: The c.748C>T SNP was genotyped from blood DNA of 182 patients
      after completing initial cancer treatments. For evaluating prognosis of genotype
      groups, associations were performed with Gleason score (GS) and biochemical
      recurrence free survival (bRFS) in patients demonstrating PSA-recurrence after
      initial cancer therapy. RESULTS: Overall distribution of the CC, CT and TT
      genotypes for the SNP was 48%, 44% and 8%, respectively. The distribution of high
      (8-10), moderate (5-7) and low (2-4) GS among the genotype groups was 17%, 74%
      and 9% for CC group compared to 25%, 74% and 1% for the CT/TT (P=0.04). Median
      bRFS time for CT/TT group was 36.5 months compared to 44.5 months for the CC
      group (P=0.16), while genotype groups combined with morphology revealed
      significantly different bRFS (P=0.004). CONCLUSIONS: This exploratory analysis in
      prostate cancer patients revealed the W allele of the KLK2 R250W SNP to be less
      likely associated with low GS morphology. Further studies will be needed to
      confirm this observation in larger cohorts.

PMID- 21178269
TI  - Evaluation of human neutrophil peptide-1, -2 and -3 as serum markers for
      colorectal cancer.
AB  - Increased total serum concentrations of human neutrophil peptide-1, -2 and -3
      (HNP-1, -2 and -3) have been associated with colorectal cancer (CRC). Owing to a
      recently developed and fully validated liquid-chromatography coupled to tandem
      mass spectrometry (LC-MS/MS) assay, individual serum concentrations of these
      antimicrobial peptides were quantified to evaluate their role as serum markers in
      CRC. Serum was obtained from patients with indications for colonoscopy,
      subsequently diagnosed as normal colon or hyperplastic polyp (CON; n= 368),
      adenomatous polyp (AP; n = 179) or colorectal cancer (CRC; n = 69). Comparison of
      HNP-1, -2 and -3 concentrations between CRC and CON (130 +/- 90 vs. 105 +/- 80;
      264 +/- 140 vs. 206 +/- 99 and 62 +/- 56 vs. 54 +/- 59 for HNP-1, -2 and -3,
      respectively) revealed that reported up-regulated total HNP-concentrations can be
      largely attributed to increased HNP-2 (P=0.0006) and HNP-1 (P=0.024) levels.
      Although receiver operating characteristics (ROC) analyses showed low specificity
      of the peptides for CRC and no significant changes in serum levels were observed
      after surgical removal of the tumor (n=23), the established differentiation
      between the HNP-subtypes may be particularly useful to completely elucidate the
      role of these antimicrobial peptides in CRC.

PMID- 21178270
TI  - Combined immunodeficiency associated with DOCK8 mutations and related
      immunodeficiencies.

PMID- 21178271
TI  - Clinical manifestations of hyper IgE syndromes.
AB  - Over the last 4 years, three genetic etiologies of hyper IgE syndromes have been
      identified: STAT3, DOCK8, and Tyk2. All of these hyper IgE syndromes are
      characterized by eczema, sinopulmonary infections, and greatly elevated serum
      IgE. However, each has distinct clinical manifestations. Mutations in STAT3 cause
      autosomal dominant HIES (Job's syndrome), which is unique in its diversity of
      connective tissue, skeletal, and vascular abnormalities. DOCK8 deficiency is
      characterized by severe cutaneous viral infections such as warts, and a
      predisposition to malignancies at a young age. Only one individual has been
      identified with a hyper IgE phenotype associated with Tyk2 deficiency, which is
      characterized by nontuberculous mycobacterial infection. The identification of
      these genetic etiologies is leading to advances in understanding the pathogenesis
      of these syndromes with the goal of improving treatment.

PMID- 21178272
TI  - Genetic, clinical, and laboratory markers for DOCK8 immunodeficiency syndrome.
AB  - DOCK8 immunodeficiency syndrome (DIDS) is a combined immunodeficiency
      characterized by recurrent viral infections, severe atopy, and early onset
      malignancy. Genetic studies revealed large, unique deletions in patients from
      different families and ethnic backgrounds. Clinical markers of DIDS include
      atopic dermatitis, allergies, cutaneous viral infections, recurrent respiratory
      tract infections, and malignancy. Immune assessments showed T cell lymphopenia,
      hyper-IgE, hypo-IgM, and eosinophilia. The impaired lymphocyte functions in DIDS
      patients appear central for disease pathogenesis.

PMID- 21178273
TI  - The essential role of DOCK8 in humoral immunity.
AB  - The processes that normally generate and maintain adaptive immunity and
      immunological memory are poorly understood, and yet of fundamental importance
      when infectious diseases place such a major economic and social burden on the
      world's health and agriculture systems. Defects in these mechanisms also underlie
      the many forms of human primary immunodeficiency. Identifying these mechanisms in
      a systematic way is therefore important if we are to develop better strategies
      for treating and preventing infection, inherited disease, transplant rejection
      and autoimmunity. In this review we describe a genome-wide screen in mice for the
      genes important for generating these adaptive responses, and describe two
      independent DOCK8 mutant mice strains identified by this screen. DOCK 8 was found
      to play an essential role in humoral immune responses and to be important in the
      proper formation of the B cell immunological synapse.

PMID- 21178274
TI  - DOCK8 immune deficiency as a model for primary cytoskeletal dysfunction.
AB  - DOCK8 deficiency is a newly described primary immune deficiency resulting in
      profound susceptibility to cutaneous viral infections, elevated IgE levels, and
      eosinophilia, but lacking in the skeletal manifestations commonly seen in hyper
      IgE syndrome, which it otherwise resembles. Although little is known about the
      DOCK8 protein, it resembles other atypical guanine exchange factors in the DOCK
      family, and is known to bind to CDC42. This suggests that a likely role for DOCK8
      is in modulating signals that trigger cytoskeletal reorganization. As a result,
      DOCK8 may also be related to other immune deficiencies that involve the
      cytoskeleton and Rho GTPase signaling pathways, such as Wiskott-Aldrich syndrome
      and Rac2 deficiency.

PMID- 21178275
TI  - The Wiskott-Aldrich syndrome: The actin cytoskeleton and immune cell function.
AB  - Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive primary
      immunodeficiency characterised by immune dysregulation, microthrombocytopaenia,
      eczema and lymphoid malignancies. Mutations in the WAS gene can lead to distinct
      syndrome variations which largely, although not exclusively, depend upon the
      mutation. Premature termination and deletions abrogate Wiskott-Aldrich syndrome
      protein (WASp) expression and lead to severe disease (WAS). Missense mutations
      usually result in reduced protein expression and the phenotypically milder X
      linked thrombocytopenia (XLT) or attenuated WAS [1-3]. More recently however
      novel activating mutations have been described that give rise to X-linked
      neutropenia (XLN), a third syndrome defined by neutropenia with variable
      myelodysplasia [4-6]. WASP is key in transducing signals from the cell surface to
      the actin cytoskeleton, and a lack of WASp results in cytoskeletal defects that
      compromise multiple aspects of normal cellular activity including proliferation,
      phagocytosis, immune synapse formation, adhesion and directed migration.

PMID- 21178276
TI  - Rac GTPases in human diseases.
AB  - Rho GTPases are members of the Ras superfamily of GTPases that regulate a wide
      variety of cellular functions. While Rho GTPase pathways have been implicated in
      various pathological conditions in humans, to date coding mutations in only the
      hematopoietic specific GTPase, RAC2, have been found to cause a human disease, a
      severe phagocytic immunodeficiency characterized by life-threatening infections
      in infancy. Interestingly, the phenotype was predicted by a mouse knock-out of
      Rac2 and resembles leukocyte adhesion deficiency (LAD). Here we review Rho
      GTPases with a specific focus on Rac GTPases. In particular, we discuss a new
      understanding of the unique and overlapping roles of Rac2 in blood cells that has
      developed since the generation of mice deficient in Rac1, Rac2 and Rac3 proteins.
      We propose that Rac2 mutations leading to disease be termed LAD type IV.

PMID- 21178277
TI  - CXCL12/CXCR4-axis dysfunctions: Markers of the rare immunodeficiency disorder
      WHIM syndrome.
AB  - The WHIM syndrome features susceptibility to human Papillomavirus infection
      induced warts and carcinomas, hypogammaglobulinemia, recurrent bacterial
      infections, B and T-cell lymphopenia, and neutropenia associated with retention
      of senescent neutrophils in the bone marrow (i.e. myelokathexis). This rare
      disorder is mostly linked to inherited heterozygous autosomal dominant mutations
      in the gene encoding CXCR4, a G protein coupled receptor with a unique ligand,
      the chemokine CXCL12/SDF-1. Some individuals who have full clinical forms of the
      syndrome carry a wild type CXCR4 gene. In spite of this genetic heterogeneity,
      leukocytes from WHIM patients share in common dysfunctions of the CXCR4-mediated
      signaling pathway upon exposure to CXCL12. Dysfunctions are characterized by
      impaired desensitization and receptor internalization, which are associated with
      enhanced responses to the chemokine. Our increasing understanding of the
      mechanisms that account for the aberrant CXCL12/CXCR4-mediated responses is
      beginning to provide insight into the pathogenesis of the disorder. As a result
      we can expect to identify markers of the WHIM syndrome, as well as other
      disorders with WHIM-like features that are associated with dysfunctions of the
      CXCL12/CXCR4 axis.

PMID- 21178278
TI  - Epidermodysplasia verruciformis and susceptibility to HPV.
AB  - PURPOSE OF REVIEW: Epidermodysplasia verruciformis has been addressed in depth in
      the recent literature despite its rarity. The disease is characterized by a
      persistence in human papillomavirus infections and development of cutaneous
      malignancies, usually happening more frequently and at a younger age than in the
      general population. Because of the role of immunodeficiency to viral antigens
      eventually leading to cancer, EV has become a model for understanding a viral
      role in cutaneous oncogenesis. Susceptibility loci for EV have been mapped and
      encoded protein functions are becoming better understood. Discoveries of novel
      mutations and further study of EV-associated HPV serotypes in lesional and
      nonlesional skin of affected patients and the general population may help
      generate a cohesive theory regarding the true role of a defective immune barrier
      in oncogenesis.

PMID- 21178279
TI  - A new radiopharmaceutical compound (131I-PR81) for radioimmunotherapy of breast
      cancer: labeling of antibody and its quality control.
AB  - PR81 is a monoclonal antibody that binds with high affinity to MUC1, which is
      over expressed on breast and other tumors. The objective of this study was to
      evaluate the application of this antibody against MUC1 as a
      radioimmunotherapeutical agent. Monoclonal antibody (PR81) against MUC1 was
      prepared, characterized, purified, and labeled with 131I. The immunoreactivity of
      radiolabeled mAb PR81with MUC1 (the native protein), BSA-P20 (a 20 amino acid
      corresponding the tandem repeat of MUC1) and MCF7 cell line were performed by
      RIA. In vitro stability of radiolabeled mAb in human serum was determined by thin
      layer chromatography (TLC). Cell toxicity and in vitro internalization studies
      were performed with the MCF7 cell line, and the tissue biodistribution of the
      radioiodinated PR81 was evaluated in normal BALB/c mice at 4, 24 and 48 hrs. The
      tumor imaging was performed in BALB/c mice with breast xenograft tumors at 24 and
      72 hr after the complex injection. The labeling efficiency was found to be 59.9%
      +/- 7.9%. MAb-131I conjugates showed high immunoreactivity towards MUC1 protein,
      BSA-P20 and MCF7 cell line. In vitro stability of the labeled product in human
      serum was found to be more than %50 over 24 hr. Cell toxicity and in vitro
      internalization studies showed that the mAb-131I conjugate inhibited 80% growth
      of the MCF7 cultured cell lines in vitro in a high concentration and up to %60 of
      the conjugate internalized after 24 h. Biodistribution studies were performed in
      normal BALB/c mice at 4, 24 and 48 hrs post-injection and no important
      accumulation was observed in vital organs. The tumors were visualized with high
      sensitivity after 24 and 72 hr in radioimmunoscintographical studies. These
      results show that the new radiopharmaceutical may be considered as a promising
      candidate for therapy of breast cancer.

PMID- 21178280
TI  - IgG isotype, glycosylation, and EGFR expression determine the induction of
      antibody-dependent cellular cytotoxicity in vitro by cetuximab.
AB  - PURPOSE: To evaluate the antibody-dependent cellular cytotoxicity (ADCC) of
      cetuximab, an anti-epidermal growth factor receptor (EGFR) IgG1 antibody, in
      vitro. METHODS: Binding to human Fc receptors was measured by ELISA. ADCC against
      a panel of tumor cell lines was evaluated using peripheral blood mononuclear
      cells or NK cells as effectors and lactate dehydrogenase release as a marker of
      cell killing. Cetuximab was compared with two glycan variants of cetuximab and
      with panitumumab, an anti-EGFR IgG2. RESULTS: Cetuximab bound with high affinity
      to FcgammaRI (EC50 = 0.13 nM) and FcgammaRIIIa (EC50 = 6 nM) and effectively
      induced ADCC across multiple tumor cell lines. Panitumumab and aglycosylated
      cetuximab did not bind to FcgammaRI or FcgammaRIIIa nor have ADCC activity even
      at high effector-target cell ratios, even though the EGFR-binding affinity of
      cetuximab and panitumumab were shown to be comparable (KD = 87 pM and 83 pM,
      respectively). The extent of cetuximab-elicited ADCC was associated with the
      level of EGFR expression on tumor cells. CONCLUSIONS: Cetuximab elicits effective
      ADCC activity against a wide range of tumor cells in vitro. This activity is
      dependent on antibody glycosylation and IgG1 isotype as well as tumor-cell EGFR
      expression. These findings suggest that ADCC may contribute to the antitumor
      activity of cetuximab.

PMID- 21178281
TI  - Epitope analysis of peanut allergen Ara h1 with human monoclonal IgM antibody
      clone #86.
AB  - A human-mouse hybridoma clone #86 secreting IgM-class human monoclonal antibody
      to peanut allergen protein Ara h1 was newly established. To detect an antibody
      binding sequence (epitope) on Ara h1, the monoclonal antibody #86 was reacted
      with multi-pin apparatus with a series of peptides synthesized from the amino
      acid sequence of Ara h1. The antibody #86 was found to bind to a peptide with
      amino acid sequence of 481EEEEDEDEEEEGSNREVRRY500. Further analysis with shorter
      pin-peptides with ten amino acid-long showed that the peptides reacted with the
      antibody #86 contained a sequence of 485DEDEEEE491. This might be an essential
      linear sequence of this epitope. When the 485DED487 part of the peptide was
      replaced by alanine, decreased binding of antibody #86 was observed.

PMID- 21178282
TI  - Preparation and in vitro evaluation of 111In-CHX-A"-DTPA-labeled anti-VEGF
      monoclonal antibody bevacizumab.
AB  - Bevacizumab is a humanized monoclonal antibody that binds to vascular endothelial
      growth factor (VEGF) and prevents tumor angiogenesis. Radionuclide imaging using
      radiolabeled bevacizumab might be useful for selection of patients for anti-VEGF
      therapy. This study describes preparation of a potential imaging agent, 111In-CHX
      A"-DTPA-bevacizumab, and evaluation of specificity of its binding to three tumor
      cell lines, SKOV3, LS174T and DU 145. Bevacizumab was conjugated with CHX-A"-DTPA
      and radiolabeled with 111In with high yield and excellent stability. Specificity
      of cellular binding was examined by a saturation assay using 100-fold excess of
      non-radiolabeled antibody. SKOV3 and LS174T tumor cell lines showed significantly
      specific binding, while DU 145 cells did not showed any specific binding. The
      specific binding is dependent to type of cell lines, which it is important for
      selection of tumor model for scintigraphic imaging of the VEGF expression.

PMID- 21178283
TI  - A fully human monoclonal antibody to Staphylococcus aureus iron regulated surface
      determinant B (IsdB) with functional activity in vitro and in vivo.
AB  - A fully human monoclonal antibody (CS-D7, IgG1) specific for the iron regulated
      surface determinant B (IsdB) of Staphylococcus aureus was isolated from the
      Cambridge Antibody Technology (CAT) scFv antibody library. As compared to
      previously described IsdB specific murine monoclonals, CS-D7 has a unique, non
      overlapping binding site on IsdB, and exhibits increased in vivo activity. The
      antibody recognizes a conformational epitope spanning amino acids 50 to 285 and
      has a binding affinity of 340 (+/- 75) pM for IsdB. CS-D7 bound to a wide variety
      of S. aureus strains, but not to an isdB deletion mutant. The antibody mediated
      opsonophagocytic (OP) killing in vitro and mediated significant protection in
      vivo. In a murine lethal sepsis model, the antibody conferred protection from
      death when dosed prior to challenge, but not when dosed after challenge.
      Importantly, in a central venous catheter (CVC) model in rats, the antibody
      reduced bacteremia and prevented colonization of indwelling catheters. Protection
      was observed when rats were dosed with CS-D7 prior to challenge as well as post
      challenge. IsdB is currently being investigated for clinical efficacy against S.
      aureus infection, and the activity of this human IsdB specific antibody
      supplements the growing body of evidence to support targeting this antigen for
      vaccine development.

PMID- 21178284
TI  - Scientific truth or false hope? Understanding Alzheimer's disease from an aging
      perspective.
AB  - In this paper, we argue that the current official definition for Alzheimer's
      disease is misleading, since it defines senile dementia (SD), a long-known
      incurable senile/geriatric condition, as a discrete/curable disease. This overly
      optimistic definition was incepted in the 1970s amid the public's fear of the
      upcoming SD crisis and desperate hope for a cure. Scientifically, however, it has
      overturned Alois Alzheimer's age-based concept for disease classification-the
      essence of modern Geriatric Medicine and the National Institute of Aging. Thus,
      the current definition for SD, though socially and politically appealing, would
      be scientifically flawed. As an authoritative study guideline, it has caused
      profound and far-reaching confusions in research by misleading attention to the
      presumptive pathogenic/erroneous factors as drug targets for "silver bullets".
      Such well-intentioned studies would generate numerous data, but render SD a
      scientific and logical enigma. In this context we discuss: 1) why and how senile
      conditions including SD differ from discrete diseases by origin, thus also by
      study paradigm and intervention strategy; 2) why senile conditions may not be
      explained by abnormal/pathogenic factors, but logically should be explained by
      "normal" elements in life, perhaps advanced aging plus risk factors; and 3) why
      the "amyloid-beta toxicity" controversy, a simple scientific issue, has lasted
      for so long. Finally, we ask: can scientific inquiry preserve its integrity and
      objectivity under social pressure? It appears that these fundamental questions
      warrant serious attention if the scientific nature of SD is to be eventually
      understood.

PMID- 21178285
TI  - Strain- and age-related alteration of proteins in the brain of SAMP8 and SAMR1
      mice.
AB  - In order to discover and identify the key protein biomarkers in the aging
      process, we performed a differential proteomic analysis of hippocampus and cortex
      in 5- and 15-month old senescence-accelerated mouse prone 8 (SAMP8) as well as in
      control strain SAM/resistant 1 (SAMR1). Using 2-DE combined with MALDI TOF/TOF
      mass spectrometry, about 1700 protein spots were isolated, and three groups of
      differentially expressed proteins were identified. The first group contained the
      strain-specific and non-age-related differential proteins that were
      differentially expressed in SAMP8 compared with SAMR1 mice. The changes might be
      implicated in the genetic difference between SAMP8 and SAMR1 mice; specifically,
      the proteins ubiquitin carboxyl-terminal esterase L3, mitofilin, adenylate kinase
      4, and an unnamed protein product (gi|12847201). The proteins in the second group
      were age-specific, which were differentially expressed between 5- and 15-month
      old SAM mice. Those proteins are particularly interesting since the changes were
      aging-related and some of them were previously reported to be expressed in
      Alzheimer's disease patients. These proteins included N-myc downstream regulated
      gene 2, enolase 2, Cu/Zn superoxide dismutase, myosin, and two unnamed protein
      products (gi|74214304 and gi|74178239). The protein in the third group was SAMP8
      specific-age-related protein, which was identified as heme binding protein 1. The
      present study provides new information about SAMP8 specific and aging-related
      protein changes in brain. Further investigations will be performed to reveal the
      significance of these proteins in brain aging process and the potential roles as
      biomarkers for effective diagnosis and therapy.

PMID- 21178286
TI  - A nationwide survey on the prevalence of dementia and mild cognitive impairment
      in South Korea.
AB  - We investigated the prevalence of dementia and mild cognitive impairment (MCI)
      and the factors associate with risk of dementia from a representative nationwide
      sample of Korean elders. 8,199 randomly-sampled Koreans aged 65 years or older
      were invited to participate in the Phase I screening assessment using Mini-Mental
      State Examination by door-to-door home visit, and 6,141 subjects (response rate =
      74.9%) responded. Among them, 2,336 subjects were invited to participate in the
      Phase II diagnostic assessment for dementia and MCI, and 1,673 subjects responded
      (response rate = 71.6%). Diagnostic assessments were administered using the
      Korean version of the Consortium to Establish a Registry for Alzheimer's Disease
      Assessment Packet (CERAD-K) Clinical Assessment Battery. The CERAD-K
      Neuropsychological Assessment Battery was used for diagnosing MCI. Age-, gender-,
      education-, and urbanicity-standardized prevalence of dementia was estimated to
      be 8.1% (95% CI = 6.9-9.2) for overall dementia and 24.1% (95% CI = 21.0-27.2)
      for MCI. Alzheimer's disease (AD) was the most prevalent type (5.7%) followed by
      vascular dementia (2.0%). Amnestic subtype (20.1%) was much more prevalent than
      nonamnestic subtype in MCI (4.0%). Older age, being male, lower education level,
      illiteracy, smoking, and histories of head trauma or depression were associated
      with increased dementia risk, and alcohol use and moderately intense exercise
      were associated with decreased dementia risk. We expect numbers of dementia
      patients to double every 20 years until 2050 in Korea and expect AD to account
      for progressively more dementia cases in the future.

PMID- 21178287
TI  - Signaling via amyloid precursor-like proteins APLP1 and APLP2.
AB  - The amyloid-beta protein precursor (AbetaPP) has been implicated in Alzheimer's
      disease (AD) not only as a precursor of the amyloid-beta peptide but also as a
      mediator of signal transduction. We recently identified novel mediators of
      AbetaPP signaling via interactions with Mint/X11 family proteins Mint1 and Mint3.
      These mediators include transcriptional co-activators Taz and Yap. Here we show
      that Taz and Yap also mediate signaling via the AbetaPP paralogues APLP1 and
      APLP2 through interactions with Mint1 and Mint3. APLP1 and APLP2 formed
      transcriptionally active triple protein complexes with the adaptor protein Mint3
      and each of the transcriptional regulators Taz and Yap, and complex formation was
      regulated by the gamma-secretase cleavage of APLP1 and APLP2. The presence of
      Mint1 instead of Mint3 in the complex prevented its translocation to the nucleus.
      APLP1 displayed much lower transactivation levels compared to AbetaPP and APLP2.
      These results indicate that all three AbetaPP family members are capable of
      activating gene transcription via Mint3-Taz and Mint3-Yap.

PMID- 21178288
TI  - Prognostic role of high-sensitivity cardiac troponin T in patients with
      nonischemic dilated cardiomyopathy.
AB  - BACKGROUND: Cardiac troponin T (cTnT) is useful biomarker in patients with
      chronic heart failure (CHF). However, its clinical use is limited by the low
      sensitivity of the conventional commercial assay system. Recently, a highly
      sensitive cTnT (hs-cTnT) assay has become commercially available. METHODS AND
      RESULTS: To compare the prognostic value of conventional cTnT and hs-cTnT in
      patients with nonischemic dilated cardiomyopathy (DCM), hemodynamic parameters
      and the serum levels of conventional cTnT, hs-cTnT and brain natriuretic peptide
      (BNP) were measured in 85 consecutive CHF patients with nonischemic DCM and then
      these patients were followed for a mean of 4.1 years. During long-term follow up,
      there were 20 cardiac deaths. In 85 DCM patients, conventional cTnT was elevated
      (>=0.03ng/ml) in 4 patients (5%) and hs-cTnT was elevated (>=0.01ng/ml) in 46
      patients (54%). In non-survivors (n=20), conventional cTnT was elevated
      (>=0.03ng/ml) in 2 patients (2%) and hs-cTnT was elevated (>=0.01ng/ml) in 17
      patients (85%). In the stepwise multivariate analyses, a high plasma level of BNP
      (P=0.002), low left ventricular ejection fraction (<30%, P=0.012) and high hs
      cTnT (>=0.01ng/ml, P=0.006) were independent significant prognostic predictors,
      but conventional cTnT (>=0.03ng/ml) was not. CONCLUSIONS: The findings of the
      present study indicated that a high serum concentration of hs-cTnT is a useful
      prognostic predictor that is independent of LVEF or BNP in CHF patients with non
      ischemic DCM, suggesting that an increased hs-cTnT concentration sensitively
      reflects ongoing myocardial damage.

PMID- 21178289
TI  - Comparison of QT/RR relation based on a 15-s averaged ECG and a single beat ECG
      during atrial fibrillation.
AB  - BACKGROUND: The aim of this study was to compare QT/RR relation based on a 15-s
      averaged beat ECG with a single beat ECG during atrial fibrillation (AF) and to
      determine which was better to estimate the QT interval after sinus restoration.
      METHODS AND RESULTS: QT and RR intervals were measured using an automatic QT
      analyzing system in 33 patients who had both AF and sinus rhythm on the same 24-h
      Holter ECG recording. In 14 patients, antiarrhythmic drugs (AAD) were
      administered. QT/RR relations were analyzed from ECG waves obtained by the
      summation of consecutive QRS-T complexes during each 15-s period (QT/RR-average)
      and a single beat QRS-T (QT/RR-single). During sinus rhythm, the slope of QT/RR
      average did not differ from that of QT/RR-single in patients with and without
      AAD. On the other hand, during AF, the slope of QT/RR-average was significantly
      greater than that of QT/RR-single (without AAD: 0.12+/-0.06 vs. 0.06+/-0.03,
      P<0.001; with AAD: 0.15+/-0.05 vs. 0.08+/-0.04, P<0.001). During AF, the QT
      interval at an RR interval of 1.2-s (QT-1.2) determined from QT/RR-average was
      significantly greater than QT-1.2 from QT/RR-single in patients with and without
      AAD. QT-1.2 in QT/RR-single during AF was significantly smaller than that during
      sinus rhythm but QT-1.2 in QT/RR-average during AF was not. CONCLUSIONS: The QT
      interval after sinus restoration could be estimated better using QT/RR-average
      than using QT/RR-single during AF.

PMID- 21178290
TI  - Biological variation of brain natriuretic peptide and cardiac events in stable
      outpatients with nonischemic chronic heart failure.
AB  - BACKGROUND: To evaluate the biological variation and prognostic value of brain
      natriuretic peptide (BNP) for stable outpatients with nonischemic chronic heart
      failure (NICHF). METHODS AND RESULTS: Biological variation in BNP was evaluated
      using an automated assay system in 140 outpatients with NICHF. The stable
      clinical condition during the 2-month study period was defined as unchanged NYHA
      and unchanged left ventricular ejection fraction; therefore, 7 patients were
      excluded during the 2 months. Thereafter, 133 patients were prospectively
      followed and the relationship between cardiac events and the plasma BNP
      concentrations (at baseline and after 2 months) were evaluated as well as the
      changes in BNP. The biological variation in BNP (2-month interval) was calculated
      as 22.3%. During a mean follow-up period of 42 months, 26 patients had cardiac
      events. According to stepwise multivariate analyses, plasma BNP after 2 months
      (P=0.0002) and % change in BNP (P=0.0067) were significant independent predictors
      of cardiac events. CONCLUSIONS: These findings indicated that a combination of
      the absolute value of BNP after 2 months and % increase in BNP (2-month interval)
      is useful for predicting cardiac events in stable outpatients with NICHF.

PMID- 21178291
TI  - Pathophysiology of aortic stenosis and approach to treatment with percutaneous
      valve implantation.
AB  - Aortic stenosis (AS) is the most commonly acquired valvular heart disease in the
      Western world (2-7% of the population aged > 65 years) and the mortality for
      untreated symptomatic severe AS is up to 50-60% at 2 years in high-risk patients.
      This review summarizes laboratory and recent clinical investigations concerning
      AS and current best treatment. Particular emphasis will be placed on
      pathophysiology and on the concept of after load mismatch and preload reserve in
      which left ventricular function is proportionately matched to level of left
      ventricular pressure, mainly because such studies carry important implications
      for both treatment with transcatheter aortic valve implantation (TAVI) and
      prognosis. Surgical aortic valve replacement is currently the gold-standard
      treatment for patients with severe symptomatic AS. Without surgery, the prognosis
      is extremely poor, with a 3-year survival rate < 30%. However, 33% of all
      patients aged >= 75 years with severe AS are declined for surgery. TAVI was
      recently introduced as a new therapeutic option for patients with AS, so the
      current indications, the technical differences between 2 different transcatheter
      aortic valves and the clinical available data will be also examined in detail. 

PMID- 21178292
TI  - Roles of cyclic adenosine monophosphate signaling in endothelial cell
      differentiation and arterial-venous specification during vascular development.
AB  - Cyclic adenosine monophosphate (cAMP) is an important second messenger mediating
      physiological functions, including metabolism, gene expression, cell growth and
      differentiation. Recently, we demonstrated novel roles of cAMP pathway in
      endothelial cell (EC) differentiation and arterial-venous specification using an
      embryonic stem cell differentiation system. These studies offered a concept that
      vascular formation is accomplished by a 2-layered mechanism: (1) a basal
      mechanism for common EC differentiation, whereby vascular endothelial growth
      factor (VEGF) signaling plays a central role in the basal mechanism, and (2) a
      vascular diversification mechanism working on the basis of common EC
      differentiation. Vascular diversification, such as artery and vein formation, can
      be only achieved by enacting specific machineries in the presence of the basal EC
      machinery. cAMP/protein kinase A signaling contributes to common EC
      differentiation through upregulation of the VEGF-A receptors, Flk1 and
      neuropilin1. On the other hand, cAMP can activate phosphatidylinositol-3 kinase,
      which induces an arterial fate in vascular progenitors via dual activation of
      Notch and beta-catenin signaling as an arterial-specific machinery. cAMP
      signaling thus plays a pivotal role in both the basal and diversification
      machinery during vascular development.

PMID- 21178293
TI  - Coronary artery calcification and cerebral small vessel disease. Association of
      systemic atherosclerosis.

PMID- 21178294
TI  - Is measuring oxidative stress useful in predicting organ-damage in respect of
      cardio-renal relations?

PMID- 21178295
TI  - Combined assessment of myocardial perfusion and function by ECG-gated myocardial
      perfusion single-photon emission computed tomography for the prediction of future
      cardiac events in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: The mid-term prognostic significance of ECG-gated single-photon
      emission computed tomography (SPECT) remains unclear in Japanese patients with
      type 2 diabetes mellitus (DM). In the present study rates of future cardiac
      events (nonfatal acute myocardial infarction (AMI), cardiac death (CD) and severe
      heart failure (HF) requiring hospitalization) were compared in patients with and
      without DM. METHODS AND RESULTS: 1,810 patients (563 DM and 1,247 non-DM) we
      followed for a mean of 26.3+/-15.5 months. Summed stress score (SSS), summed
      difference score (SDS), poststress ejection fraction (EF) and resting end
      diastolic volume (EDV) were calculated. In total, 20 cases of AMI (9 in DM
      (1.59%) and 11 in non-DM (0.88%)), 20 of CD (7 in DM patients (1.24%) and 13 in
      non-DM (1.04%)) and 54 of severe HF (31 in DM (5.5%) and 23 in non-DM (1.84%))
      occurred. Univariate Cox analysis showed that, in DM patients, predictors of
      total cardiac events were poststress EF (Wald 60.4; P<0.001), resting EDV (Wald
      53.8; P<0.001), SSS (Wald 39.6; P<0.001), SDS (Wald 26.1; P<0.001), history of
      prior MI (Wald 4.32; P<0.05) and hemoglobin A(1c) value (Wald 4.30; P<0.05).
      Multivariate Cox analysis showed that poststress EF (Wald 9.85; P<0.01) and SDS
      (Wald 6.19; P<0.01) were independent predictors of total cardiac events.
      CONCLUSIONS: Combined assessment of perfusion and function by ECG-gated SPECT may
      predict future cardiac events in type 2 DM patients.

PMID- 21178296
TI  - Epicardial adipose tissue radiodensity is independently related to coronary
      atherosclerosis. A multidetector computed tomography study.
AB  - BACKGROUND: Preliminary research indicates that epicardial adipose tissue (EAT)
      may display both anti- and proatherosclerotic properties. Because the varying
      radiodensities of selected human tissues assessed by multidetector computed
      tomography (MDCT) has been shown to reflect differences in biological
      characteristics, the present study investigated the hypothesis that the
      proatherosclerotic properties of EAT may be linked to its radiodensity. METHODS
      AND RESULTS: The study included 164 consecutive patients (82 females, mean age
      58.8+/-11.1 years) with suspected coronary artery disease (CAD) undergoing MDCT
      coronary angiography. Coronary atherosclerosis was defined as: (1) CAD (ie,
      presence of at least 1 coronary stenosis >=50%) and (2) coronary artery calcium
      (CAC) determined by Agatston score. EAT radiodensity was assessed by MDCT and
      averaged 81.00+/-4.64 HU (Hounsfield unit (HU) scale). Mean CAC score was 96.0+/
      220.0. Patients with CAD (n=36) showed higher EAT radiodensity than patients
      without CAD (78.99+/-4.12 vs. -81.57+/-4.64 HU, P<0.01). In the multivariable
      model, only EAT radiodensity and age were independently associated with CAD (odds
      ratio (OR) 1.15, 95%confidence interval (CI) 1.04-1.28; OR 1.08, 95%CI 1.04-1.12;
      respectively). EAT radiodensity also correlated with CAC score (r=0.23, P<0.01).
      EAT radiodensity (P<0.001), age (P<0.001), sex (P=0.03), and past smoking
      (P<0.01) were independent correlates of CAC in the multivariable linear
      regression model. CONCLUSIONS: Increased EAT radiodensity is independently
      associated with coronary atherosclerosis, which may reflect the unfavorable,
      proatherosclerotic metabolic properties of more radiodense epicardial fat.

PMID- 21178297
TI  - Prevalence of vitreous hemorrhage following coronary revascularization in
      patients with diabetic retinopathy.
AB  - BACKGROUND: In patients with diabetic retinopathy (DR), vitreous hemorrhage (VH)
      is a common complication that threatens visual acuity and hence, quality of life.
      A considerable number of DR patients at risk of VH require coronary
      revascularization, but little is known about the prevalence of VH after coronary
      revascularization. METHODS AND RESULTS: This study investigated 151 patients with
      DR who were followed up by ophthalmologists between April 2004 and September
      2008, and underwent coronary revascularization (coronary artery bypass surgery
      n=36 or drug-eluting stent implantation n=115). At the time of coronary
      revascularization 56 had non-proliferative DR (NPDR) and 95 had proliferative DR
      (PDR). During an average follow-up of 531 days after revascularization, VH
      occurred in 24 (15.9%) patients, 18 (11.9%) of whom experienced VH within 6
      months of the procedure. In VH patients, PDR rather than NPDR predominated as the
      background to VH (21 vs. 3, respectively). The 1-year prevalence of VH was higher
      in patients with PDR than in those with NPDR (22.0% vs. 1.9%, P=0.0055).
      CONCLUSIONS: VH is not a rare complication following coronary revascularization
      among patients with DR, especially in those with PDR. Thus, in terms of
      maintaining quality of life, VH after coronary revascularization needs further
      attention in these patients.

PMID- 21178298
TI  - Cardioprotective effects of luteolin during ischemia-reperfusion injury in rats.
AB  - BACKGROUND: Antioxidants effectively reduce ischemia-reperfusion (IR) injury. The
      cardioprotective effects of luteolin, a flavonoid that exhibits antioxidant
      properties and is widely available in many fruits and vegetables, were examined
      in rats subjected to myocardial IR injury. METHODS AND RESULTS: Rats were
      subjected to myocardial ischemia or reperfusion injury to evaluate the
      antiarrhythmic effects of luteolin. Myocardial infarct size was determined
      histochemically with triphenyltetrazolium chloride staining of the left
      ventricle. Luteolin was administered intravenously 15min before occlusion of the
      coronary artery. The incidence and duration of ventricular tachycardia and
      ventricular fibrillation and mortality during myocardial ischemia were
      significantly reduced by luteolin (10ug/kg). Similarly, luteolin (1ug/kg) reduced
      ventricular arrhythmias and mortality during the reperfusion phase. Pretreatment
      with luteolin decreased plasma lactate dehydrogenase and nitric oxide (NO)
      levels. Luteolin (10ug/kg) significantly reduced the myocardial infarct size, as
      well as malondialdehyde production in tissue samples of myocardial IR injury.
      Luteolin also downregulated inducible NO synthase protein and mRNA expression,
      but did not significantly alter neuronal NO synthase or endothelial NO synthase
      expression. CONCLUSIONS: Luteolin is capable of protecting the myocardium against
      IR injury. The actions of luteolin are at least partly mediated through
      downregulation of NO production and its own antioxidant properties.

PMID- 21178299
TI  - Genetic variability and haplotype profile of MDR1 (ABCB1) in Roma and Hungarian
      population samples with a review of the literature.
AB  - The genetic variability, haplotype profile and ethnic differences of MDR1
      polymorphisms in healthy Roma and Hungarian populations were analyzed and the
      results were compared with those of other populations available from the
      literature. Healthy subjects (465 Roma and 503 Hungarian) were genotyped for
      C1236T, G2677T/A and C3435T variants of MDR1 by PCR-RFLP assay. Differences were
      found between the Roma and Hungarian populations in the frequencies of MDR1 1236
      CC (20.7 vs. 33.2%) and TT genotypes (30.8 vs. 21.9%), in T allele frequency
      (0.551 vs. 0.443) (p < 0.002), and in 3435T allele frequency (0.482 vs. 0.527, p
      < 0.04). Furthermore, the frequency of CGC, CGT and CTT haplotypes was
      significantly higher in the Hungarian population than in Roma (41.4 vs. 35.3%,
      9.04 vs. 6.02% and 2.88 vs. 1.08%, respectively; p < 0.009), whereas the
      frequency of TGC and TTC haplotypes was higher in the Roma population than in the
      Hungarian (7.31 vs. 1.68% and 6.67 vs. 2.08%, respectively; p < 0.001). The
      prevalence of MDR1 polymorphisms in the Hungarian population is similar to that
      of other European populations; however, some differences were observed in the
      haplotype structures. In contrast, the Roma population differs from Hungarians,
      from Caucasians and from populations from India in the incidence of MDR1 common
      variants and haplotypes.

PMID- 21178300
TI  - Drug-induced idiosyncratic hepatotoxicity: prevention strategy developed after
      the troglitazone case.
AB  - Troglitazone induced an idiosyncratic, hepatocellular injury-type hepatotoxicity
      in humans. Statistically, double null genotype of glutathione S-transferase
      isoforms, GSTT1 and GSTM1, was a risk factor, indicating a low activity of the
      susceptible patients in scavenging chemically reactive metabolites. CYP3A4 and
      CYP2C8 were involved in the metabolic activation and CYP3A4 was inducible by
      repeated administrations of troglitazone. The genotype analysis, however,
      indicated that the metabolic idiosyncrasy resides in the degradation of but not
      in the production of the toxic metabolites of troglitazone. Antibody against
      hepatic aldolase B was detected in the case patients, suggesting involvement of
      immune reaction in the toxic mechanism. Troglitazone induced apoptotic cell death
      in human hepatocytes at a high concentration, and this property may have served
      as the immunological danger signal, which is thought to play an important role in
      activating immune reactions. Hypothesis is proposed in analogy to the virus
      induced hepatitis. After the troglitazone-case, pharmaceutical companies
      implemented screening systems for chemically reactive metabolites at early stage
      of drug development, taking both the amount of covalent binding to the proteins
      in vitro and the assumed clinical dose level into consideration. At the post
      marketing stage, gene analyses of the case patients, if any, to find
      pharmacogenetic biomarkers could be a powerful tool for contraindicating to the
      risky patients.

PMID- 21178301
TI  - Inhibitory effects of Phyllanthus amarus and its major lignans on human
      microsomal cytochrome P450 activities: evidence for CYP3A4 mechanism-based
      inhibition.
AB  - Phyllanthus amarus has long been used as a herbal medicine in several countries.
      Phytochemicals in herbal medicine may interact with cytochromes P450 (CYP) and
      thus raise the potential of herb-drug interactions; therefore, the inhibitory
      effects of P. amarus and its major phytochemicals phyllanthin and hypophyllanthin
      on CYP isoforms were determined using human liver microsomes and selective
      substrates. Both ethanolic and aqueous extracts of P. amarus inhibited CYP1A2,
      CYP2D6, CYP2E1 and CYP3A4 in a dose-dependent manner. Compared to known CYP3A
      inhibitors, the IC(50) values of the ethanolic and aqueous extracts on
      testosterone 6beta-hydroxylation were higher than that of ketoconazole but were
      lower than those of erythromycin and clarithromycin. Both extracts were weak
      inhibitors of CYP1A2, CYP2D6 and CYP2E1. In addition, phyllanthin and
      hypophyllanthin were potent mechanism-based inhibitors of CYP3A4 with K(I) values
      of 1.75 +/- 1.20 uM and 2.24 +/- 1.84 uM and k(inact) values of 0.18 +/- 0.05
      min(-1) and 0.15 +/- 0.06 min(-1), respectively. The k(inact)/K(I) ratios of
      these lignans were higher than those reported for some therapeutic drugs that act
      as mechanism-based inhibitors of CYP3A4. These results suggest that co
      administration of P. amarus with drugs that are metabolized by CYP3A4 may
      potentially result in herb-drug interactions.

PMID- 21178302
TI  - Deglycosylated ginsenosides are more potent inducers of CYP1A1, CYP1A2 and CYP3A4
      expression in HepG2 cells than glycosylated ginsenosides.
AB  - Ginseng is one of the most commonly used herbal medicines worldwide. Ginsenosides
      are believed to be responsible for the therapeutic activities of ginseng;
      however, co-administration of prescription drugs with ginseng products may give
      rise to ginseng-drug interactions. Cytochrome P450 enzymes are major phase I
      enzymes involved in the metabolism of most currently used drugs. Inhibition or
      induction of P450 enzymes can lead to pharmacokinetic drug interactions. Previous
      reports on ginseng-drug interactions have been controversial and confusing. In
      the present study, we examined the effects of thirteen ginsenosides on the
      expression of CYP1A1, CYP1A2 and CYP3A4 in HepG2 cells. We found that eight
      ginsenosides and aglycones potently induced CYP1A1 expression, and that structure
      activity relationships existed for these effects. Moreover, we discovered that
      deglycosylated ginsenosides, some of which are putative ginsenoside metabolites,
      were more potent inducers of CYP1A1, CYP1A2 and CYP3A4 than glycosylated
      ginsenosides. This finding indicates that ginsenoside metabolites may partially
      account for ginseng-drug interactions, and that differences in the composition of
      intestinal bacteria and the extent of deglycosylation of the ginsenosides could
      be a contributing factor to the inconsistencies observed in previous clinical and
      pre-clinical studies with regard to ginseng-drug interactions.

PMID- 21178305
TI  - Molecular evidence that most RNAs required for germination and pollen tube growth
      are stored in the mature pollen grain in petunia.
AB  - After landing on the stigma, the pollen grain germinates and elongates a tube to
      deliver its generative nuclei to the egg cell of the ovule. The molecular
      mechanisms involved in the drastic morphological changes in the pollen grain
      during this fertilization process remain largely unknown. In this study, the
      expression of 732 randomly selected genes in petunia pollen and pollen tubes was
      analyzed by microarray and quantitative PCR analyses. We found no evidence for up
      regulation of any of these genes in the pollen tube. Our findings provide support
      at the gene level for the longstanding hypothesis that pollen germination and
      tube growth are not dependent on new RNA synthesis and that the large number of
      RNAs required for germination and tube growth are stored in mature pollen grains.

PMID- 21178304
TI  - Genetic analysis of DNA repair in the hyperthermophilic archaeon, Thermococcus
      kodakaraensis.
AB  - Extensive biochemical and structural analyses have been performed on the putative
      DNA repair proteins of hyperthermophilic archaea, in contrast to the few genetic
      analyses of the genes encoding these proteins. Accordingly, little is known about
      the repair pathways used by archaeal cells at high temperature. Here, we
      attempted to disrupt the genes encoding the potential repair proteins in the
      genome of the hyperthermophilic archaeon Thermococcus kodakaraensis. We succeeded
      in isolating null mutants of the hjc, hef, hjm, xpb, and xpd genes, but not the
      radA, rad50, mre11, herA, nurA, and xpg/fen1 genes. Phenotypic analyses of the
      gene-disrupted strains showed that the xpb and xpd null mutants are only slightly
      sensitive to ultraviolet (UV) irradiation, methyl methanesulfonate (MMS) and
      mitomycin C (MMC), as compared with the wild-type strain. The hjm null mutant
      showed sensitivity specifically to mitomycin C. On the other hand, the null
      mutants of the hjc gene lacked increasing sensitivity to any type of DNA damage.
      The Hef protein is particularly important for maintaining genome homeostasis, by
      functioning in the repair of a wide variety of DNA damage in T. kodakaraensis
      cells. Deletion of the entire hef gene or of the segments encoding either its
      nuclease or helicase domain produced similar phenotypes. The high sensitivity of
      the Deltahef mutants to MMC suggests that Hef performs a critical function in the
      repair process of DNA interstrand cross-links. These damage-sensitivity profiles
      suggest that the archaeal DNA repair system has processes depending on repair
      related proteins different from those of eukaryotic and bacterial DNA repair
      systems using homologous repair proteins analyzed here.

PMID- 21178306
TI  - Allelic interaction at seed-shattering loci in the genetic backgrounds of wild
      and cultivated rice species.
AB  - It is known that the common cultivated rice (Oryza sativa) was domesticated from
      Asian wild rice, O. rufipogon. Among the morphological differences between them,
      loss of seed shattering is one of the striking characters specific for the
      cultivated forms. In order to understand the genetic control on shattering habit,
      QTL analysis was carried out using BC(2)F(1) backcross population between O.
      sativa cv. Nipponbare (a recurrent parent) and O. rufipogon acc. W630 (a donor
      parent). As a result, two strong QTLs were detected on chromosomes 1 and 4, and
      they were found to be identical to the two major seed-shattering loci, qSH1 and
      sh4, respectively. The allelic interaction at these loci was further examined
      using two sets of backcross populations having reciprocal genetic backgrounds,
      cultivated and wild. In the genetic background of cultivated rice, the wild qSH1
      allele has stronger effect on seed shattering than that of sh4. In addition, the
      wild alleles at both qSH1 and sh4 loci showed semi-dominant effects. On the other
      hand, in the genetic background of wild rice, non-shattering effects of
      Nipponbare alleles at both loci were examined to inspect rice domestication from
      a viewpoint of seed shattering. It was serendipitous that the backcross plants
      individually having Nipponbare homozygous alleles at either shattering locus
      (qSH1 or sh4) shed all the seeds. This fact strongly indicates that the non
      shattering behavior was not obtained by a single mutation in the genetic
      background of wild rice. Probably, some other minor genes are still associated
      with the formation or activation of abscission layer, which enhance the seed
      shattering.

PMID- 21178307
TI  - QTL analysis for flowering time using backcross population between Oryza sativa
      Nipponbare and O. rufipogon.
AB  - In the near future, global average temperature is expected to increase due to the
      accumulation of greenhouse gases, and increased temperatures will cause severe
      sterility in many crop species. In rice, since wild species show high genetic
      variation, they may have the potential to improve the flowering characters of
      cultivars. In this study, we investigated flowering characters under natural
      conditions by comparing an Asian wild rice accession of Oryza rufipogon W630
      (originated from Myanmar) with a Japanese rice cultivar, O. sativa Japonica cv.
      Nipponbare. Further, QTL analysis for days to heading (DH) and spikelet opening
      time (SOT: the time of day when the spikelet opens) was carried out using
      BC(2)F(8) backcross population derived from the cross between them. Regarding DH,
      four QTLs were detected, and two of them were found to have wild alleles with
      strong effects leading to longer days to heading during the Japanese summer.
      These wild alleles may be used to produce late-heading cultivars that do not
      flower during the high summer temperatures anticipated in the future. As for SOT,
      two parameters of SOTb (beginning time when the first spikelet opens) and SOTm
      (median time when 50% of the spikelets open) were recorded and the time
      differences from Nipponbare were investigated. Two QTLs on chromosomes 5 and 10
      and two QTLs on chromosomes 4 and 5 were detected for SOTb and SOTm,
      respectively. The wild alleles were responsible for early spikelet opening time
      at all loci. If the wild alleles detected in this study have the same effects in
      the genetic background of other cultivars, they will be very useful in producing
      early-flowering rice cultivars that complete fertilization in the morning before
      the temperature rises.

PMID- 21178308
TI  - Production of wheat-Psathyrostachys huashanica chromosome addition lines.
AB  - Psathyrostachys huashanica Keng (2n = 14; N(h)N(h)) is an endangered wheat
      related species, with a distribution in the Huashan region of central China. It
      has many agronomically promising characters including resistance to disease and
      drought and winter hardiness. We produced hybrids between common wheat as the
      female parent and P. huashanica as the male parent. From the offspring, we
      selected chromosome addition lines of common wheat carrying each of all seven
      chromosomes of P. huashanica. Four chromosomes (B, D, E and F) were recovered in
      disomic lines and three (A, C and G) in monosomic addition lines. These alien
      chromosomes were distinguished from each other by cytological analyses.
      Chromosome A was characterized by a 45S rDNA site in the subtelomeric region of
      the short arm. Chromosome B carried one 5S and one 45S rDNA sites co-localized in
      an interstitial region of the short arm, and the expression of the alien high
      molecular-weight glutenin was observed in the endosperm of line B. Chromosome D
      had a 45S rDNA signal in the interstitial region of the long arm. Chromosomes C,
      E, and F were distinguished by the EST-SSR markers Ltc0464, Ltc0096, and Xcfe175,
      respectively. The homoeologous group of each alien chromosome was implied from
      the results above, and the utilization of these addition lines for wheat breeding
      was discussed.

PMID- 21178309
TI  - CiMutT, an asidian MutT homologue, has a 7, 8-dihydro-8-oxo-dGTP
      pyrophosphohydrolase activity responsible for sanitization of oxidized
      nucleotides in Ciona intestinalis.
AB  - The oxidized nucleotide precursors 7, 8-dihydro-8-oxo-dGTP (8-oxo-dGTP) and 1, 2
      dihydro-2-oxo-dATP (2-oxo-dATP) are readily incorporated into nascent DNA strands
      during replication, which would cause base substitution mutations. E. coli MutT
      and human homologue hMTH1 hydrolyze 8-oxo-dGTP, thereby preventing mutations. In
      this study, we searched for hMTH1 homologues in the ascidian Ciona intestinalis
      using the NCBI-BLAST database. Among several candidates, we focused on one open
      reading frame, designated as CiMutT, because of its high degree of identity
      (41.7%) and similarity (58.3%) to the overall amino acid sequence of hMTH1,
      including the Nudix box. CiMutT significantly suppressed the mutator activity of
      E. coli mutT mutant. Purified CiMutT had a pyrophosphohydrolase activity that
      hydrolyzed 8-oxo-dGTP to 8-oxo-dGMP and inorganic pyrophosphate. It had a pH
      optimum of 9.5 and Mg(++) requirement with optimal activity at 5 mM. The activity
      of CiMutT for 8-oxo-dGTP was comparable to that of hMTH1, while it was 100-fold
      lower for 2-oxo-dATP than that of hMTH1. These facts indicate that CiMutT is a
      functional homologue of E. coli MutT. In addition, the enzyme hydrolyzed all four
      of the unoxidized nucleoside triphosphates, with a preference for dATP. The
      specific activity for 8-oxo-dGTP was greater than that for unoxidized dATP and
      dGTP. These results suggest that CiMutT has the potential to prevent mutations by
      8-oxo-dGTP in C. intestinalis.

PMID- 21178310
TI  - Simple techniques to increase the production yield and enhance the quality of
      organic rice bran oils.
AB  - This study develops simple techniques for increasing production yield and
      refining of crude RBO (CRBO). It was found that pre-heating of rice bran by hot
      air oven to reach 60 degrees C before being extracted by screw press machine
      increased the yield from 4.8 to 8.3%w/w. This paper suggested three simple steps
      for refining of organic CRBO: (1) filtering using filter papers (2) sedimentation
      by adding 4%w/v fuller's earth and (3) bleaching by running through a packed
      column of activated carbon. These steps significantly enhanced the qualities of
      RBO when compared to CRBO before treatment. It was found that the lightness of
      oil as indicated by color value (L*) increased from 22.8 to 28.7, gum and wax
      decreased from 3.6 to 1.3%w/w. However, the simple refining method had no effect
      on peroxide value and free fatty acid content. Moreover, it slightly induced the
      loss of oryzanol content from 2.8 to 2.2%w/w.

PMID- 21178311
TI  - Use of immobilized Pseudomonas sp. as whole cell catalyst for the
      transesterification of used cotton seed oil.
AB  - Lipase enzyme producing bacteria, Pseudomonas sp., have been grown at varying oil
      concentrations to make it adaptive for high oil concentrations and it was found
      to show the maximum growth and maximum lipase activity when 40- and 30-vol% of
      oil respectively was used as a source of carbon in growth medium. Bacteria was
      immobilized with sodium alginate and used as whole cell catalyst for the
      transesterification of used cotton seed oil. Preliminary experiments resulted
      about 70% transesterification of used cotton seed oil with methanol as calculated
      by proton NMR technique.

PMID- 21178312
TI  - Metabolism and synthesis of lipids in the polyunsaturated fatty acid-producing
      fungus Mortierella alliacea.
AB  - The fungal strain Mortierella alliacea YN-15 is a promising industrial producer
      of polyunsaturated fatty acids (PUFAs), in particular arachidonic acid. In order
      to more efficiently produce PUFAs, the metabolism of an externally supplied plant
      oil, alpha-linolenic acid (ALA)-rich linseed triacylglycerol (TAG), was examined,
      and time-dependent changes in the composition of its lipid and fatty acid
      metabolites were traced. Addition of linseed TAG to growing cultures resulted in
      a transient increase in extracellular 1,2-diacylglycerol (DAG), and even more so
      of 1,3-DAG, in the mycelia. This was followed by a decrease in both DAGs and an
      increase in TAG. Eicosapentaenoic acid (EPA), a desaturated and elongated product
      of ALA, accumulated to a greater extent in cellular phospholipids than in neutral
      lipids. Moreover, the addition of ALA in free fatty acid form to the culture led
      to the generation of EPA. However, EPA production was not observed upon addition
      of ALA-rich 1,2- or 1,3-DAG, indicating that fatty acids released from exogenous
      lipids were used for resynthesis of mycelial TAG. These results suggested that
      TAG might be hydrolyzed by extracellular lipases, whereas its synthesis might be
      catalyzed by intracellular enzymes. Appropriate regulation of such enzymes might
      be an effective strategy to enhance PUFA production under plant oil
      supplementation.

PMID- 21178313
TI  - Development of karanja oil based offset printing ink in comparison with linseed
      oil.
AB  - The conventional offset lithographic printing ink is mainly based on linseed oil.
      But in recent years, due to stiff competition from synthetic substitutes mainly
      from petroleum products, the crop production shrinks down to an unsustainable
      level, which increases the price of linseed oil. Though soyabean oil has replaced
      a major portion of linseed oil, it is also necessary to develop alternate cost
      effective vegetable oils for printing ink industry. The present study aims to
      evaluate the performance of karanja oil (Pongamia glabra) as an alternative of
      linseed oil in the formulation of offset printing ink because karanja oil is
      easily available in rural India. Physical properties of raw karanja oil are
      measured and compared with that of alkali refined linseed oil. Rosin modified
      phenolic resin based varnishes were made with linseed oil as well as with karanja
      oil and their properties are compared. Sheetfed offset inks of process colour
      yellow and cyan is chosen to evaluate the effect of karanja oil in ink
      properties. In conclusion, karanja oil can be accepted as an alternate vegetable
      oil source with its noticeable effect on print and post print properties with
      slower drying time on paper. However, the colour and odour of the oil will
      restrict its usage on offset inks.

PMID- 21178314
TI  - Preparation of TiO2 thin films using octadecylamine Langmuir-Blodgett films and
      evaluation of their photocatalytic activity.
AB  - A study was conducted to demonstrate that nanometer-thick titanium dioxide
      (TiO(2)) thin films could be prepared by the hydrolysis of titanium potassium
      oxalate using octadecylamine (ODA) Langmuir-Blodgett (LB) films as templates. The
      amount of TiO(2) generated in the LB film was found to be proportional to the
      number of deposited ODA layers, which enables precise control of the TiO(2) film
      thickness. After heat treatment of the LB films at 300-600 degrees C, the
      photocatalytic activities of the resulting TiO(2) films were determined from the
      decomposition of stearic acid cast films when irradiated with UV light for
      different time periods. Higher photocatalytic activity was observed in TiO(2)
      films heat treated at lower temperatures.

PMID- 21178315
TI  - Preparation and evaluation of liquid-crystal formulations with skin-permeation
      enhancing abilities for entrapped drugs.
AB  - The usefulness of liquid crystals (LC) in topical formulations for application to
      skin was evaluated by measuring the in vitro permeation profile of a model
      compound, calcein, entrapped in a LC formulation, through excised hairless rat
      skin and a three-dimensional cultured human-skin model; the viability was
      determined using the MTT assay. Two physically stable LCs were prepared from a
      mixture of mono-, di-, and tri-esters 1, and monoesters 2, composed of erythritol
      and phytanylacetic acid. Cryo-transmission electron microscopy (cryo-TEM),
      electron diffraction patterns, and small-angle X-ray diffraction (SAXS)
      observations of the LC nanodispersions showed that the structures of the LCs were
      reverse hexagonal (LC-A) and cubic (LC-B). The skin-permeation properties of
      calcein were enhanced by entrapping in the LCs as a result of the increase in
      calcein partition from the LC dispersion solution into the skin; the properties
      were analyzed using a skin-permeation-time profile. Drug partitioning could also
      be modified by the LC structure. No skin damage was caused by the LC formulation
      in these experiments.The present study suggests that LC dispersions are potential
      additives in topical drug formulations and cosmetic formulations.

PMID- 21178316
TI  - Lipase-catalyzed synthesis of fattythioic acids from palm oil.
AB  - The present work focuses on the synthesis of fattythioic acids (FTAs) by a one
      step lipase catalyzed reaction of palm oil with carbonothioic S,S-acid using
      Lipozyme. The product was characterized using Fourier transform infrared (FTIR)
      spectroscopy, proton nuclear magnetic resonance ((1)H NMR) technique and
      elemental analysis. The effects of various reaction parameters such as reaction
      time, temperature, amount of enzyme, molar ratio of substrates, and various
      organic solvents of the reaction system were investigated. The optimum conditions
      to produce FTAs were respectively, incubation time, 20 h, temperature, 40 degrees
      C, amount of enzyme, 0.05 g and molar ratio of carbonothioic S,S-acid to palm
      oil, 5.0:1.0. Hexane was the best solvent for this reaction. The conversion of
      the products at optimum conditions was around 91%.

PMID- 21178317
TI  - Pregnenolone biosynthesis in the rat salivary gland and its inhibitory effect on
      secretion.
AB  - Pregnenolone (PRG), a major neurosteroid, suppressed carbachol-induced salivary
      secretion in perfused submandibular gland in rats. These effects were enhanced
      and depressed by agonistic muscimol (MUS) and antagonistic bicuculline to the
      gamma-aminobutyric acid A receptor (GABA(A)-R), respectively. In contrast, PRG
      sulfate, a sulfate-conjugated PRG metabolite, antagonized the suppressive effects
      of MUS, resulting in upregulation of salivary secretion. Quantitative RT-PCR and
      Western blotting revealed lesser expression of the PRG synthetase CYP11A1 protein
      and mRNA in the parotid, submandibular, and sublingual gland than in the cerebral
      cortex or adrenal gland as positive control organs. However, in response to
      methamphetamine withdrawal-induced stress, CYP11A1 production in each type of the
      salivary gland was highly upregulated to levels similar to those seen in the
      cerebral cortex. These results indicate that the salivary gland is capable of
      producing neurosteroids, as well as the brain. This suggests that steroid
      biosynthesis occurs in the salivary gland and is involved in the inhibitory
      regulation of salivary secretion in cooperation with GABA(A)-R. Further studies
      are needed to determine the pathophysiological significance of the biosynthesis
      of neurosteroids and their mechanisms of action via nuclear and membrane
      receptors.

PMID- 21178318
TI  - Glucose uptake in rat skeletal muscle L6 cells is increased by low-intensity
      electrical current through the activation of the phosphatidylinositol-3-OH kinase
      (PI-3K) / Akt pathway.
AB  - Activation of Akt by insulin is transmitted via phosphatidylinositol-3-OH kinase
      (PI-3K) and enhances glucose uptake. The PI-3K/Akt signaling is diminished in
      insulin resistance. Thus, approaches that activate PI-3K/Akt signaling leading to
      improved glucose uptake may ameliorate hyperglycemia. Here we showed that low
      intensity electrical current or mild electrical stimulation (MES) activated the
      PI-3K/Akt signaling and increased the glucose uptake in rat skeletal muscle (L6)
      cells. The glucose uptake enhanced by MES in muscle cells, the major cells
      involved in glucose disposal, suggests MES may have a possible beneficial effect
      on hyperglycemia.

PMID- 21178319
TI  - The effect of aloe vera oral administration on cutaneous wound healing in type 2
      diabetic rats.
AB  - Delayed wound healing is one of the complications of diabetes mellitus. The
      present study was performed to investigate the effect of Aloe vera oral
      administration on open wounds in type 2 diabetic rats. Full thickness open wounds
      (1.5 * 1.5 cm) were created under general anesthesia on the backs of the rats.
      These rats were divided into two group, a control group (Group C) and an Aloe
      vera oral administration group (Group A). Each wound area was measured on days 1,
      2, 4 and 8 postwounding. The stages of wound granulation tissues were evaluated
      histopathologically. The expression of transforming growth factor (TGF)-beta1 and
      vascular endothelial growth factor (VEGF) were determined by
      immunohistochemically. The wounds were significantly contracted in Group A on
      days 2, 4 and 8 postwounding. Histological results revealed that the inflammatory
      cell infiltration, angiogenesis, extracellular matrix deposition and
      epithelialization were promoted in Group A, respectively. The immunohistochemical
      results revealed that both TGF-beta1 and VEGF protein-positive cells increased in
      Group A on day 4 postwounding. We concluded that Aloe vera oral administration
      accelerated wound healing in type 2 diabetic rats.

PMID- 21178320
TI  - Logistical study in Hyogo prefecture on disposal of poultry carcasses infected
      with highly pathogenic avian influenza virus to prevent infection spreading to
      other flocks.
AB  - Establishment of a disposal plan for carcasses in advance is important for
      prevention of epidemics. A disposal plan for contaminated goods such as poultry
      carcasses infected with highly pathogenic avian influenza (HPAI) virus was
      studied in Hyogo Prefecture, Japan. We investigated all poultry farms with over
      1,000 birds for their locations, species and numbers of birds, structure and size
      of poultry facilities and land spaces of the farms. Moreover, we judged whether
      they could dispose of all the carcasses at their farms. In 2005, 5.5 million
      layers and 2.7 million broilers were being kept. If HPAI had broken out, 44.0% of
      the farmers could bury all the carcasses, and 65.6% could compost them at their
      farms. However, 23.4% could not dispose of them except by burning them at
      incineration facilities. We decided to choose burning first for rapid disposal as
      long as the virus was not a pandemic type.

PMID- 21178321
TI  - A mechanism of excessive accumulation of abomasal gas in vagotomized cattle
      determined using fluoroscopy.
AB  - To better understand the mechanism of excessive gas accumulation in the abomasum
      in bovine abomasal displacement, we performed gastric fluoroscopy in vagotomized
      cattle. Fifteen 6-month-old Holstein steers were divided into three groups: a non
      vagotomized control group (Group C; n=5), a ventral thoraco-vagotomized group
      (Group V; n=5), and a dorsal and ventral thoraco-vagotomized group (Group DV;
      n=5). These groups were examined by fluoroscopy before and during a 5-week
      observation period after surgery. In Group C, no change was observed throughout
      the observation period. In Group DV, immediately after surgery, reticuloruminal
      motility was completely absent and ruminal distention was seen. Two weeks after
      surgery, abnormal reticulum motility and increased gas accumulation in the
      abomasal body were noted. Abomasal dilatation was also observed. In Group V, 1
      week after surgery, gas inflow into the abomasum and relatively normal reticulum
      motility were observed along with a rapid increase in abomasal gas. Abomasal
      dilatation was also observed. In addition, left-displaced abomasum occurred in
      one of the steers in this group. From these results, we concluded that one of the
      mechanisms of excessive gas accumulation in the abomasum is reticulum-mediated
      gas inflow from the rumen combined with vagotomy-induced hypomotility.

PMID- 21178322
TI  - Central and peripheral neurotoxic effects of ivermectin in rats.
AB  - Ivermectin is considered a very safe drug; however, there are reports of toxic
      effects in particularly sensitive populations or due to accidental overdose. The
      aim of this study was (1) to further characterize the central and peripheral
      toxic effects of ivermectin in animals and (2) to determine possible therapeutic
      strategies for use in cases of ivermectin poisoning. We tested the effects of
      experimental doses of ivermectin previously reported to cause various intensities
      of CNS depression. However, in our study, ivermectin at 2.5, 5.0 and 7.5 mg/kg
      i.v. did not produce visible CNS depression in rats and 10 mg/kg resulted in
      sleepiness and staggering 10 to 40 min after application, while a dose of 15
      mg/kg caused CNS depression very similar to general anesthesia. Ivermectin dose
      dependently potentiates thiopentone-induced sleeping time in rats. Flumazenil
      (0.2 mg/kg), the benzodiazepine antagonist, did not affect the action of
      thiopentone; however, it significantly reduced sleeping time in rats treated with
      a combination of ivermectin (10 mg/kg) and thiopentone (25 mg/kg; from 189.86 +/-
      45.28 min to 83.13 +/- 32.22 min; mean +/- SD). Ivermectin causes an increase in
      the tonus (EC(50)=50.18 uM) and contraction amplitude (EC(50)=59.32 uM) of
      isolated guinea pig ileum, very similar to GABA, but without the initial
      relaxation period. These effects are dose-dependent and sensitive to atropine.
      Our results confirm the central and peripheral GABAergic properties of ivermectin
      in mammals and also indicate involvement of the cholinergic system in its
      toxicity. In addition, the results suggest that flumazenil and atropine have
      potential clinical roles in the treatment of ivermectin toxicity.

PMID- 21178323
TI  - Equivalent clinical outcomes of bleeding peptic ulcers in teaching and non
      teaching hospitals: evidence for standardization of medical care in Japan.
AB  - The clinical outcomes of treatments for several medical conditions are better in
      teaching hospitals than in non-teaching hospitals. However, there is only limited
      information for comparisons of the clinical outcomes of bleeding peptic ulcers
      between teaching and non-teaching hospitals. A total of 4,863 patients treated by
      endoscopic hemostasis on admission for bleeding peptic ulcers were evaluated in
      586 hospitals of the Diagnosis Procedure Combination (DPC) system. We collected
      their data from the database associated with the DPC system to compare the risk
      adjusted length of stay (LOS) and in-hospital mortality within 30 days with
      respect to the hospital characteristics. The hospitals were categorized into two
      groups: teaching hospitals that were certified by the Japanese Society of
      Gastroenterology (3,332 patients in 360 hospitals) and non-teaching hospitals
      (1,531 patients in 226 hospitals). There was no significant difference with
      regard to the mean LOS and the crude in-hospital mortality within 30 days between
      groups (p = 0.181 and 0.174, respectively). Multiple linear regression analyses
      revealed that the hospital characteristics were not associated with the risk
      adjusted LOS. The standardized coefficient for non-teaching hospitals was 0.019
      (p = 0.172). Multiple logistic regression analyses further showed no significant
      difference in the in-hospital mortality within 30 days (non-teaching hospitals,
      odds ratio = 1.35, 95% confidence interval = 0.786 - 2.319, p = 0.277). In
      conclusion, both teaching and non-teaching hospitals have equivalent qualities in
      management of bleeding peptic ulcers. These findings suggest that the
      standardization of medical treatments for bleeding peptic ulcers has become
      disseminated in Japan.

PMID- 21178324
TI  - Public support for the use of newborn screening dried blood spots in health
      research.
AB  - OBJECTIVES: The level of support among Michigan adults for the use of residual
      newborn screening dried blood spots (DBS) was investigated. METHODS: We analyzed
      data from 4 questions on the 2008 Michigan Behavioral Risk Factor Surveillance
      System (n = 3,108). The questions asked about general support for the use of DBS
      for research and for research investigating childhood diseases, adult diseases
      and diseases related to environmental exposures. RESULTS: The majority of adults
      (72.3%) favored the use of DBS for research intended to benefit the health of
      residents. With more question specificity, a higher proportion of adults (84.2%
      86.8%) were found to favor the use of DBS for research, and a lower proportion
      had no opinion. The odds of favoring use were higher among those who were
      younger, female, white, healthy, or with at least a high school degree.
      CONCLUSIONS: This is the first population survey of adult attitudes regarding use
      of DBS for different types of health research, with results showing considerable
      public support. The findings are being used in community outreach efforts and
      highlight the need to investigate opposition in vulnerable populations.

PMID- 21178325
TI  - In situ reversed ileocystoplasty for less invasive augmentation cystoplasty: an
      experimental study.
AB  - PURPOSE: To evaluate the application of a reversed intact ileal patch for
      augmentation cystoplasty in terms of improvements in bladder urodynamics and to
      eliminate the need for bowel anastomosis in an experimental model. METHODS: 12
      cross-bred adult dogs were used for reversed seromuscular ileocystoplasty with
      intact bowel segment. The procedure was comprised of selecting a 7- to 10-cm
      ileal loop from about 20 cm proximal to the ileocecal valve. The seromuscular
      layer of the ileal loop from its antimesenteric aspect was sutured to the bladder
      mucosa of the previously bivalved bladder with running stitches. RESULTS: 10
      animals survived and completed their 4-week follow-up period. Postoperative
      urodynamic study revealed a 26% increase of mean maximal cystometric capacity
      [from 226 to 285 ml (p = 0.002)] and a significant increase in mean bladder
      compliance [from 11.8 to 17.8 ml/cm H(2)O (p = 0.002)]. Mean maximal detrusor
      filling pressure decreased significantly from 20 to 16.1 cm H(2)O (p = 0.011).
      Histopathologic examination of the augmented bladder showed complete
      epithelialization of the serosal surface of ileum with layers of transitional
      urothelium. CONCLUSIONS: The early results of this less invasive technique were
      promising in terms of improvements in bladder urodynamic variables and growth of
      transitional urothelium. Longer follow-up is necessary to show the durability of
      these effects.

PMID- 21178326
TI  - Identification of bacterial DNA in noninfectious pleural fluid with a highly
      sensitive PCR method.
AB  - BACKGROUND: Bacterial DNA due to bacterial translocation has been identified in
      noninfectious ascitic fluid samples. OBJECTIVE: This study investigated the
      possible presence of bacterial DNA in the pleural fluid of patients with pleural
      effusions of noninfectious origin, using a highly sensitive PCR-based method.
      METHODS: Pleural fluid samples from 175 patients (average age +/- SD: 69 +/- 14
      years) with noninfectious pleural effusion (62 transudates, 113 exudates) were
      analyzed. Bacterial DNA was detected using nested PCR with amplification of a
      fragment of the gene r16S, with 2 amplification protocols, i.e. low sensitivity
      (10 and 40 cycles) and high sensitivity (40 and 40 cycles). RESULTS: With the
      less sensitive amplification process, only 1 sample was positive (Haemophilus
      parainfluenzae in a patient with hepatic hydrothorax). With the highly sensitive
      nested PCR method, bacterial DNA was identified in the pleural fluid, of both
      transudative and exudative origin, of 75 of the 175 patients (43%). In cases of
      isolation of a single bacterium, the more frequent were Escherichia coli,
      Salmonella enterica and Streptococcus pneumoniae. CONCLUSIONS: Regardless of its
      origin, bacterial DNA can be identified in almost half of noninfectious pleural
      effusions by using a highly sensitive PCR-based method. The possible clinical
      significance or prognostic value of these findings deserves to be evaluated.

PMID- 21178327
TI  - CD22 regulates adaptive and innate immune responses of B cells.
AB  - B cells sense microenvironments through the B cell receptor (BCR) and Toll-like
      receptors (TLRs). While signals from BCR and TLRs synergize to distinguish self
      from nonself, inappropriate regulation can result in development of autoimmune
      disease. Here we show that CD22, an inhibitory co-receptor of BCR, also
      negatively regulates TLR signaling in B cells. CD22-deficient (Cd22(-/-)) B cells
      exhibit hyperactivation in response to ligands of TLRs 3, 4 and 9. Evidence
      suggests that this results from impaired induction of suppressors of cytokine
      signaling 1 and 3, well-known suppressors of TLR signaling. Antibody-mediated
      sequestration of CD22 on wild-type (WT) B cells augments proliferation by TLR
      ligands. Conversely, expression of CD22 in a Cd22(-/-) B cell line blunts
      responses to TLR ligands. We also show that lipopolysaccharide-induced
      transcription by nuclear factor-kappaB is inhibited by ectopic expression of CD22
      in a TLR4 reporter cell line. Taken together, these results suggest that negative
      regulation of TLR signaling is an intrinsic property of CD22. Since TLRs and BCR
      activate B cells through different signaling pathways, and are differentially
      localized in B cells, CD22 exhibits a broader regulation of receptors that
      mediate adaptive and innate immune responses of B cells than previously
      recognized.

PMID- 21178328
TI  - False positive newborn screening results are not always benign.
AB  - OBJECTIVE: Our goal was to assess the impact on families of receiving abnormal
      newborn screening results. PATIENTS AND METHODS: We conducted telephone
      interviews with parents of 3 groups of children who had received abnormal newborn
      screening results: (1) false positive but otherwise healthy (FP, n = 28), (2)
      true positive (TP, n = 20), and (3) false positive with other medical conditions
      (FP + other, n = 12). Interviews, based on the instruments developed by Waisbren
      et al. [J Pediatr Psychol 2004;29:565-570], included open- and close-ended
      questions as well as the Parental Stress Index (PSI). RESULTS: In response to
      open ended questions, FP parents expressed concern about having more children and
      identified numerous problems with how they were told about newborn screening.
      Parents of FP + other reported the most stress, followed by parents of children
      with metabolic disease. Nonetheless, almost 10% of FP parents reported clinically
      significant stress as well as worry about their child's health and future.
      CONCLUSIONS: False positive newborn screening results cause some parents to
      experience stress and long-term worry. Although more work is needed to learn how
      well these sequelae can be averted by more effective communication in the pre-
      and postnatal periods, these effects need to be considered in deciding whether to
      add new disorders to newborn screening panels.

PMID- 21178329
TI  - Elevated amh gene expression in the brain of male tilapia (Oreochromis niloticus)
      during testis differentiation.
AB  - Anti-mullerian hormone (AMH) is expressed in male embryos and represses
      development of mullerian ducts during testis differentiation in mammals, birds
      and reptiles. Amh orthologues have been identified in teleosts despite them
      lacking mullerian ducts. Previously we found sexually dimorphic aromatase
      activity in tilapia brains before ovarian differentiation. This prompted us to
      search for further dimorphisms in tilapia brains during sex differentiation and
      see whether amh is expressed. We cloned the tilapia amh gene and found that it
      contains 7 exons but no spliced forms. The putative protein presents highest
      homologies with Amh proteins of pejerrey and medaka as compared to other
      Perciformes. We analysed amh expression in adult tissues and found elevated
      levels in testes, ovary and brain. Amh expression was dimorphic with higher
      levels in XY male brains at 10-15 dpf, when the gonads were still
      undifferentiated and gonadal amh was not dimorphic. Male brains had 2.7-fold
      higher amh expression than gonads. Thereafter, amh levels decreased in the brain
      while they were up-regulated in differentiating testes. Our study indicates that
      amh is transcribed in male brains already at 10 dpf, suggesting that sexual
      differentiation may be occurring earlier in tilapia brain than in gonads.

PMID- 21178330
TI  - Visualization of fine-scale genomic structure by oligonucleotide-based high
      resolution FISH.
AB  - The discovery of complex structural variations that exist within individual
      genomes has prompted a need to visualize chromosomes at a higher resolution than
      previously possible. To address this concern, we established a robust, high
      resolution fluorescence in situ hybridization (FISH) method that utilizes probes
      derived from high complexity libraries of long oligonucleotides (>150 mers)
      synthesized in massively parallel reactions. In silico selected oligonucleotides,
      targeted to only the most informative elements in 18 genomic regions of interest,
      eliminated the need for suppressive hybridization reagents. Because of the
      inherent flexibility in our probe design methods, we readily visualized regions
      as small as 6.7 kb with high specificity on human metaphase chromosomes,
      resulting in an overall success rate of 94%. Two-color FISH over a 479-kb
      duplication, initially reported as being identical in 2 individuals, revealed
      distinct 2-color patterns representing direct and inverted duplicons,
      demonstrating that visualization by high-resolution FISH provides further insight
      in the fine-scale complexity of genomic structures. The ability to design FISH
      probes for any sequenced genome along with the ease, reproducibility, and high
      level of accuracy of this technique suggests that it will be powerful for routine
      analysis of previously difficult genomic regions and structures.

PMID- 21178331
TI  - The CD6 scavenger receptor is differentially expressed on a CD56 natural killer
      cell subpopulation and contributes to natural killer-derived cytokine and
      chemokine secretion.
AB  - The CD6 scavenger receptor is known to be expressed on virtually all T cells and
      is supposed to be involved in costimulation, synapse formation, thymic selection
      and leukocyte migration. Here, we demonstrate that CD6 is differentially
      expressed by a subpopulation of peripheral CD56(dim) natural killer (NK) cells
      and absent on CD56(bright) NK cells. CD56(dim)CD16(+) cells represent the major
      NK subset in the periphery, and most cells within this group are positive for
      CD6. Most killer immunoglobulin-like receptor- and immunoglobulin-like transcript
      positive cells also belong to the CD6(+) subpopulation, as expected from their
      restricted expression on CD56(dim) NK cells. In addition, CD6(+) NK cells are
      similar to the newly identified CD94(low)CD56(dim) NK subpopulation and most
      distant from the recently defined CD27(+) NK subpopulation based on the reverse
      correlation of expression between CD6 and CD27, a marker associated primarily
      with CD56(bright) NK cells. With respect to CD6 function on NK cells, direct CD6
      triggering did not result in degranulation but induced secretion of cytokines
      (interferon-gamma and tumor necrosis factor-alpha) and chemokines [CXCL10 (IP
      10), CXCL1 (GRO-alpha)]. Thus, CD6 expression on peripheral NK cells marks a
      novel CD56(dim) subpopulation associated with distinct patterns of cytokine and
      chemokine secretion.

PMID- 21178332
TI  - Low aryl hydrocarbon receptor-interacting protein expression is a better marker
      of invasiveness in somatotropinomas than Ki-67 and p53.
AB  - BACKGROUND: Some pituitary adenomas exhibit fast growth and invade surrounding
      structures. To date, there is no robust marker to predict invasiveness. AIM: To
      evaluate Ki-67, p53 and aryl hydrocarbon receptor-interacting protein (AIP)
      expression and compare these between invasive and noninvasive somatotropinomas
      and nonfunctioning pituitary adenomas (NFPAs). METHODS: Protein expression was
      determined by immunohistochemistry. Tumors were classified according to
      percentage of immunolabeled nuclei for Ki-67 and p53. AIP immunopositivity was
      graded according to a score encompassing pattern and intensity. Invasiveness was
      defined according to radiological and surgical criteria. RESULTS: Thirty-eight
      sporadic somatotropinomas were studied. Median Ki-67 labeling index in invasive
      and noninvasive tumors was 1.6 (range 0-20.6) and 0.26 (0-2.2), respectively (p =
      0.01). With a 2.3% cut-off point obtained by ROC curve analysis, invasive
      adenomas were distinguished with 100% specificity, 39% sensitivity, and 63%
      accuracy. Low AIP expression was also correlated with tumor invasiveness (p =
      0.001), with sensitivity, specificity and accuracy of 78, 80, and 79%,
      respectively. Expression of p53 was not different among tumors. Twenty-nine NFPAs
      were studied, with no significant difference between Ki-67, p53 and AIP
      expression in invasive and noninvasive tumors. High AIP expression was more
      frequent in NFPAs, with Ki-67 >3% (p = 0.051), especially when only gonadotrope
      cell adenomas (n = 25) were considered (p = 0.012). CONCLUSIONS: These data
      suggest, for the first time, that AIP is a better marker of invasiveness in
      somatotropinomas than Ki-67 and p53. In addition, low AIP expression is observed
      in invasive somatotropinomas, in contrast with high AIP expression in NFPAs
      (mainly gonadotrope cell tumors) with high proliferative indices.

PMID- 21178333
TI  - Chromosome homologies between tsessebe (Damaliscus lunatus) and Chinese muntjac
      (Muntiacus reevesi) facilitate tracing the evolutionary history of Damaliscus
      (Bovidae, Antilopinae, Alcelaphini).
AB  - Genome-wide homologies between the tsessebe (Damaliscus lunatus, 2n = 36) and
      Chinese muntjac (Muntiacus reevesi, 2n = 46) have been established by cross
      species painting with Chinese muntjac chromosome paints. Twenty-two autosomal
      painting probes detected 35 orthologous segments in the tsessebe. Hybridization
      results confirmed that: (i) D. lunatus carries the (9;14) reciprocal
      translocation that has been proposed to be a derived chromosomal landmark shared
      by all species of the Antilopinae; (ii) the karyotype of D. lunatus can be
      derived almost exclusively from the bovid ancestral karyotype through 12
      Robertsonian translocations involving 24 ancestral acrocentric autosomes; (iii)
      in addition to the Rb fusions, pericentric heterochromatic amplification has
      shaped the morphology of several of the D. lunatus chromosomes. Integrated
      analysis of these and published cytogenetic data on pecorans has allowed us to
      accurately discern the karyotype history of Damaliscus (D. lunatus; D. pygargus,
      2n = 38; D. hunteri, 2n = 44). The phylogenomic relationships of 3 species
      reflected by specific chromosomal rearrangements were consistent with published
      phylogenies based on morphology, suggesting that chromosomal rearrangements have
      played an important role in speciation within the Alcelaphini, and that karyotype
      characters are valuable phylogenetic markers in this group.

PMID- 21178334
TI  - p53-Mediated oxidative stress and tubular injury in rats with glycerol-induced
      acute kidney injury.
AB  - BACKGROUND/AIMS: p53 is a transcriptional factor that responds to severe cell
      damage promoting the transcription of proapoptotic and prooxidant genes. In this
      study, we evaluated the role of p53 activation in glycerol-induced acute kidney
      injury (Gly-AKI). METHODS: Rats were treated with p53 inhibitor (pifithrin-alpha)
      in the moment we injected glycerol. Renal function, renal histology (HE), TUNEL
      labeling, cleaved caspase-3 staining, renal p53, Bax, PUMA, Bcl-2, p21 and
      survivin expressions, renal lipid and DNA oxidative markers, and the expression
      of antioxidant enzymes (Mn-SOD, HO-1, and NAD(P)H:quinone-oxidoreductase-1) were
      evaluated. RESULTS: Gly-AKI rats showed an increased renal expression of
      phosphorylated-p53. The p53 inhibitor attenuated renal impairment and
      significantly reduced tubular injury. The expression of the oxidative markers was
      significantly reduced in treated rats. Proapoptotic and prooxidant proteins Bax
      and PUMA were overexpressed in Gly-AKI rats and reduced in treated rats. On the
      contrary, antiapoptotic Bcl-2, p21, and survivin showed a tendency to increase in
      treated rats. The antioxidant enzymes' expression remained elevated or increased
      in treated rats. CONCLUSION: On the whole, p53 inhibition was protective in the
      short term. The oxidative stress subsided and the transcription tipped toward
      prosurvival genes; consequently tubular injury was attenuated in treated rats.

PMID- 21178335
TI  - Interventions to reduce late referrals to nephrologists.
AB  - BACKGROUND: Despite the adverse health outcomes with late nephrology referral for
      patients with chronic kidney disease (CKD), little is known about the underlying
      mechanisms and reasons for late referral patterns. METHODS: We conducted a
      Medline search for peer-reviewed articles focused on nephrology referral among
      adults with CKD. We critically reviewed this literature in regard to late
      nephrology referral, highlighted its shortcomings, and provided a theoretically
      based framework for future research. RESULTS: Late referral has been attributed
      to three key types of factors: primary care provider (PCP), patient, and
      healthcare system factors. Limited empirical research has pointed to knowledge
      deficits, perceptions, and preferences by PCPs as well as to knowledge deficits,
      psychological concerns, and economic concerns by patients. The existing
      literature is severely limited by retrospective designs, closed-ended surveys,
      and the absence of a theoretically driven conceptual framework to fully evaluate
      root causes of this ongoing problem. Social Cognitive Theory may be a
      particularly well-suited conceptual model for late nephrology referral because
      important PCP and patient factors correspond to key constructs of this theory.
      CONCLUSION: Future research is needed to delineate pathways underlying reasons
      for PCPs' late referral patterns and CKD patients' referral nonadherence.
      Interventions are urgently needed to reduce late referrals and improve the health
      of patients with CKD.

PMID- 21178336
TI  - Haemodiafiltration versus high-flux haemodialysis: Effects on phosphate control
      and erythropoietin response.
AB  - INTRODUCTION: Haemodiafiltration (HDF) has been reported to improve
      erythropoietin (EPO) responsiveness and phosphate clearance. We prospectively
      audited the effect of HDF on EPO dosages, weight and serum phosphate. METHODS: 34
      patients dialyzing on Tu/Th/Sa switched to HDF, and 44 dialyzing on M/W/F
      remained on high-flux haemodialysis (HD) and were followed for 12 months.
      RESULTS: Dialysis adequacy (Kt/V start HDF 1.56 +/- 0.03 vs. HD 1.58 +/- 0.04 and
      12 months 1.55 +/- 0.03 vs. 1.59 +/- 0.03), haemoglobin (start 11.7 +/- 0.3 vs.
      11,8 +/- 0.2 g/dl and end 11.5 +/- 0.1 vs. 11.3 +/- 0.3 g/dl), weight (start 69.8
      +/- 2.4 vs. 67.8 +/- 2.5 kg and end 67.4 +/- 2.5 vs. 66.1 +/- 2.3 kg), or EPO
      prescription (start 83 (61-186) vs. 123 (71-225) IU/kg/weeks and 12 months 142
      (48-188) vs. 124 (59-223) IU/kg/weeks) did not differ. There were no differences
      in serum albumin, CRP, calcium and parathyroid hormone. Serum beta-2
      microglobulin (B2M) decreased with HDF (32.7 +/- 1.9 vs. 28.1 +/- 1.1 mg/l, p <
      0.01), but not with HD (31.6 +/- 1.4 vs. 31.5 +/- 1.1 mg/l). Serum phosphate fell
      with HDF (start 1.48 +/- 0.08 vs. 1.57 +/- 0.07 mmol/l (p = NS); 3 months 1.35 +/
      0.07 vs. 1.61 +/- 0.08; 6 months 1.34 +/- 0.06 vs. 1.57 +/- 0.06, and 12 months
      1.36 +/- 0.07 vs. 1.67 +/- 0.07, all p < 0.05). CONCLUSION: HDF did not lead to
      weight gain or improved EPO responsiveness in this prospective observational
      study. However, predialysis serum phosphate and B2M fell with HDF.

PMID- 21178337
TI  - Outcomes of patients with delayed dialysis initiation: Results from the AVENIR
      study.
AB  - BACKGROUND: Some patients who reach end-stage renal disease refuse to start
      dialysis at the time suggested by their nephrologist and delay it. Whether this
      delay may affect health-related quality of life (HRQoL), clinical and biological
      parameters at dialysis onset, and then survival and hospitalization during
      dialysis is unknown. METHODS: We considered all adult patients who began dialysis
      in Lorraine (France) in 2005-2006 having previously been followed by a
      nephrologist. Clinical and biological characteristics at dialysis onset were
      collected from medical records, and nephrologists were interviewed about
      compliance with the recommended starting date. HRQoL was measured using the
      French version of the 'Kidney Disease Quality of Life' V36 questionnaire.
      Mortality and total duration of hospitalization during the first year of dialysis
      were recorded as part of the end-stage renal disease French registry. The effects
      of delaying dialysis on survival and on duration of hospitalization were
      determined using log-rank test and polychotomous logistic regression,
      respectively. RESULTS: Of 541 patients, 88 (16.3%) declined to initiate dialysis
      at the time recommended by the nephrologist and delayed it. Compared with
      patients who were compliant with the advice, noncompliers had more comorbidities,
      poorer clinical and biological profiles at dialysis start, and a higher risk of
      beginning dialysis in emergency circumstances with greater decline in the 'burden
      of kidney disease' dimension of HRQoL. However, there were no differences in
      survival or duration of hospitalization during dialysis. CONCLUSION: Despite a
      negative effect on clinical and biological parameters at initiation, delaying
      dialysis did not impact on survival during treatment.

PMID- 21178338
TI  - Left ventricular systolic strain in chronic kidney disease and hemodialysis
      patients.
AB  - BACKGROUND: The impact of chronic kidney disease (CKD) and hemodialysis on heart
      function is not fully understood. We aimed to investigate the influence of
      different stages of CKD and maintenance hemodialysis on heart function. METHODS:
      One hundred fifty-three patients were categorized into 3 subgroups [56 without
      CKD as controls; 37 with moderate-advanced CKD, stages 3, 4 or 5, and 60 with end
      stage renal disease (ESRD) undergoing maintenance hemodialysis]. Left ventricular
      (LV) function was assessed by conventional echocardiography and 2-dimensional
      speckle-tracking echocardiography with strain analysis (2D strain analysis).
      RESULTS: There was no significant difference of gender, age and LV ejection
      fraction among groups. Compared with controls, global peak systolic longitudinal
      strain (GS(l)), circumferential strain and strain rate were decreased in the CKD
      group. Along with the decline of renal function, GS(l) deteriorated. Moreover,
      compared with moderate-advanced CKD patients, GS(l), circumferential strain and
      strain rate were better in ESRD group receiving maintenance hemodialysis.
      CONCLUSIONS: Worsening renal function was associated with a reduction of systolic
      function, and could be quantified by 2D strain analysis. The hemodialysis
      patients have better LV systolic function than the moderate-advanced CKD
      patients.

PMID- 21178339
TI  - Distribution of dexamethasone and preservation of inner ear function following
      intratympanic delivery of a gel-based formulation.
AB  - Intratympanic (IT) delivery of drugs to the ear is increasingly used for both
      clinical and research purposes. One limitation of IT delivery is that drugs are
      rapidly lost from the middle ear by a number of processes, so that prolonged
      delivery of drug is technically difficult. In the present study, the delivery
      characteristics of a poloxamer hydrogel formulation containing dexamethasone
      (dex) were evaluated. The gel is liquid at room temperature, allowing IT
      injection, but transitions to a gel at body temperature, providing a prolonged
      residence time in the middle ear. A 50-MUl volume of control or dex-containing
      gel (dex-gel) was injected through the tympanic membrane of guinea pigs. Cochlear
      function was assessed with cochlear action potential and acoustic emission
      thresholds measured immediately, 6 or 24 h after IT gel injection. After 6- or 24
      hour treatment with dex-gel, perilymph drug gradients along the cochlea were
      assessed by taking samples sequentially from the apex, and endolymph was sampled
      from the basal turn. Control gel injections caused small changes in sound field
      calibrations and functional measures for low-frequency stimuli, consistent with
      an induced conductive loss. Within 24 h, responses returned to normal. Twenty
      four hours after dex-gel injection, low-frequency changes remained as the dex-gel
      was retained better in the middle ear, but there was no indication of high
      frequency loss. While perilymph sample data showed that dex gradients were
      substantially lower than after single injections of dex solution, quantitative
      analysis of this result suggests that some dex may have entered the perilymph
      through the thin bone in the apical region of the cochlea. Endolymph levels of
      dex remained lower than those in the perilymph. This study confirms that a
      poloxamer hydrogel-based dex formulation provides an effective method for a
      prolonged delivery, providing a more uniform distribution of drug in the inner
      ear.

PMID- 21178341
TI  - Temporal trends and associated factors for pre-hospital and in-hospital delays of
      stroke patients over a 16-year period: the Athens study.
AB  - BACKGROUND: The management and outcome of acute ischemic stroke changed
      dramatically after the introduction of intravenous thrombolysis. However,
      relatively few patients have received thrombolytic treatment, mainly due to pre
      hospital and/or in-hospital delays. Although the causes of these delays have been
      adequately studied, their change over a long period has not. METHODS: All acute
      first-ever stroke patients (n = 2,746) presenting to our academic center from
      1993 to 2008 were prospectively documented in a computerized stroke data bank.
      The time from symptoms onset to presentation at the emergency room and to
      acquisition of a brain CT was calculated. Time trends over this period as well as
      the factors affecting them were analyzed. RESULTS: The final study cohort
      consisted of 2,326 acute stroke patients after excluding 302 patients with an
      unknown time of stroke onset and 118 who suffered a stroke during hospitalization
      for another illness. Over the 16-year period, the median time from stroke onset
      to presentation at the emergency room decreased significantly from 3.15 h
      (interquartile range 1.30-10.30) to 2.00 h (range 1.00-4.00) (p < 0.001). The
      median time from emergency room presentation to CT scan completion also decreased
      significantly (p < 0.001) from 12.3 h (range 4.1-29.8) to 1.0 h (range 0.31
      2.77). As a result, the proportion of patients having a CT scan within 4 h of
      stroke onset increased significantly from 8.6% in 1993-1994 to 53.6% in 2007-2008
      (p < 0.001). Thrombolytic treatment was applied in 4.15% of all ischemic stroke
      patients in the period from 2003 to 2008. Along with other significant factors,
      use of an emergency medical service was associated with a 57% greater chance of
      presenting within 3 h after symptoms onset. CONCLUSIONS: These results suggest a
      continued improvement in pre-hospital and in-hospital delays for stroke
      management. Public awareness and education regarding medical and paramedical
      services are necessary for the best early management of acute stroke patients.

PMID- 21178342
TI  - Hyperdense middle cerebral artery sign and stroke outcomes after intravenous
      thrombolysis.

PMID- 21178345
TI  - Thrombolysis at 3-4.5 hours after acute ischemic stroke onset--evidence from the
      Canadian Alteplase for Stroke Effectiveness Study (CASES) registry.
AB  - BACKGROUND: Extending the therapeutic window for thrombolysis is an important
      strategy in maximizing the proportion of patients treated. ECASS III examined a 3
      4.5-hour window and showed a benefit to treated patients. We examined the
      experience in Canadian centres using intravenous tPA treatment in the 3-4.5-hour
      time window. METHODS: The data were obtained from the CASES (Canadian Alteplase
      for Stroke Effectiveness Study)--a prospective, multicentric cohort study with
      patient enrollment from 60 centres across Canada over 2.5 years. The 90-day
      outcome, mortality and symptomatic intracranial hemorrhage of patients
      thrombolysed between 3 and 4.5 h and within 3 h of symptom onset were compared. A
      mRS 0-1 (no symptoms at all or no significant disability despite symptoms, able
      to carry out all usual duties and activities) at 90 days was defined as a
      favorable outcome. RESULTS: A total of 1,112 patients with complete data were
      included. 129 (11.6%) patients received tPA between 3 and 4.5 h of symptom onset
      and 983 (88.4%) patients received tPA within 3 h. At 90 days, 39.4% of the
      patients in the 3-4.5-hour treatment group and 36.5% of patients in the under 3
      hour treatment group attained a mRS <=1. There were no differences between the
      two groups regarding their functional status at 3 months. There was a trend
      towards higher rate of sICH in the 3-4.5-hour group compared to the 0-3-hour
      group (7.8 vs. 3.8%, p = 0.06). Similarly there was a trend towards higher rate
      of deaths in the 3-4.5-hour group compared to the 0-3-hour group (28.4 vs. 21.4%,
      p = 0.09). A chi(2) test for trend demonstrated a rising proportion of
      symptomatic ICH in later time windows (p = 0.013). A similar trend (non
      significant) was observed for mortality. CONCLUSION: Our study suggests that
      patients with acute ischemic stroke may be successfully treated with intravenous
      tPA in the 3-4.5-hour treatment window, but cautions that later time window
      treatment may result in greater adverse events.

PMID- 21178346
TI  - Treating as early as possible with thrombolysis is crucial, but can we do better
      in the sub-4.5-hour time window?

PMID- 21178344
TI  - Advances in neuroprotective strategies: potential therapies for intracerebral
      hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is associated with higher mortality and morbidity
      than any other form of stroke. However, there currently are no treatments proven
      to improve outcomes after ICH, and therefore, new effective therapies are
      urgently needed. Growing insight into ICH pathophysiology has led to the
      development of neuroprotective strategies that aim to improve the outcome through
      reduction of secondary pathologic processes. Many neuroprotectants target
      molecules or pathways involved in hematoma degradation, inflammation or
      apoptosis, and have demonstrated potential clinical benefits in experimental
      settings. We extensively reviewed the current understanding of ICH
      pathophysiology as well as promising experimental neuroprotective agents with
      particular focus on their mechanisms of action. Continued advances in ICH
      knowledge, increased understanding of neuroprotective mechanisms, and improvement
      in the ability to modulate molecular and pathologic events with multitargeting
      agents will lead to successful clinical trials and bench-to-bedside translation
      of neuroprotective strategies.

PMID- 21178347
TI  - Neurocognitive profiles of children with moyamoya disease before and after
      surgical intervention.
AB  - BACKGROUND: Clinical research on moyamoya disease (MMD) has focused on
      symptomatic outcome such as transient ischemic attacks. Neurocognitive function
      in children critically affects social outcome and is closely related to quality
      of life. This study is the first to analyze the neurocognitive profiles of
      children with MMD before and after surgery. METHODS: Sixty-five patients were
      selected out of 137 who underwent surgery for MMD between 2006 and 2008. The
      preoperative and postoperative neurocognitive function was tested using the
      Korean version of the Wechsler Intelligence Scale for Children-Revised (KEDI-WISC
      R) and the Bender Gestalt Test (BGT). Pre- and postoperative profiles of patients
      with or without major infarctions were compared. Patients with borderzone
      infarctions were analyzed as well. RESULTS: Preoperatively, patients had age
      appropriate full-scale intelligence quotient (FSIQ) and verbal IQ (VIQ) scores,
      which were maintained after surgery. There was significant improvement in
      performance IQ (PIQ) (p = 0.01) and BGT scores postoperatively (p < 0.01). Among
      the subtests, Coding showed significant improvement postoperatively (p < 0.01).
      Preoperatively, patients with major infarctions had significantly lower FSIQ (p <
      0.01), VIQ (p = 0.01) and PIQ (p < 0.01) scores compared with those without
      infarctions. The pre- and postoperative neurocognitive profiles of the patients
      with borderzone infarctions fell between those of patients with absolutely no
      infarctions and those of patients with major infarctions. CONCLUSIONS:
      Considering the natural history of MMD, which leads to a drastic decline in
      neurocognitive functions, the present findings indicate a role for early active
      surgery to save the intellectual abilities of children with MMD.

PMID- 21178348
TI  - Defining the extent of irreversible brain ischemia using perfusion computed
      tomography.
AB  - BACKGROUND: Perfusion computed tomography (PCT) shows promise in acute stroke
      assessment. However, the accuracy of CT perfusion thresholds in defining the
      acute infarct core remains uncertain. METHOD: Concurrent PCT and MRI-DWI
      performed 3-6 h after symptoms onset were assessed in 57 ischemic stroke
      patients. PCT was compared to DWI images to define the infarct core using a pixel
      based receiver operating characteristic curve analysis to calculate the area
      under the curve (AUC) for thresholds from PCT maps that were co-registered with
      the DWI slice location. RESULTS: A relative cerebral blood flow (CBF) of 45% of
      the contralateral hemisphere was found to be the most accurate threshold for
      describing the infarct core (AUC 0.788), and it was also by far the most frequent
      threshold with the highest AUC across patients. CONCLUSION: CBF thresholds on PCT
      define the acute infarct core more accurately than do other PCT thresholds,
      including a cerebral blood volume of 2 ml/100 g.

PMID- 21178349
TI  - Carotid atherosclerotic markers in CADASIL.
AB  - PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is a cerebral small vessel disease caused by
      mutations of the NOTCH3 gene. Marked variations in disease severity have raised
      the hypothesis that non-genetic factors may modulate the expressivity of the
      phenotype. The aim of the current study was to evaluate whether atherosclerosis,
      assessed by carotid duplex ultrasonography, is associated with variations in the
      clinical and MRI phenotype of CADASIL. METHODS: Data from 144 consecutive
      patients enrolled in an ongoing prospective cohort study were collected. Degree
      of disability was assessed by the modified Rankin Scale, that of cognitive
      impairment by the Mattis Dementia Rating Scale (MDRS). The total volume of the
      brain, of lacunar lesions and of white matter hyperintensities, the number of
      cerebral microhemorrhages, and parameters derived from histograms of apparent
      diffusion coefficient were measured on cerebral MRI. Atherosclerosis was
      evaluated by B-mode ultrasonography of carotid arteries. Both the carotid intima
      media thickness (cIMT) and the presence of carotid plaques or stenosis were
      recorded. RESULTS: Higher cIMT was found to be independently associated with
      lower MDRS scores when this score was less than the quartile limit (p = 0.02).
      Only a trend for a positive association was detected between cIMT and the Rankin
      score (p = 0.06). There was no significant association between carotid markers
      and the occurrence of stroke or MRI parameters except for diffusion data. The
      mean and peak values of MRI diffusion histograms were found positively associated
      with the presence of plaques (p < 0.01). CONCLUSION: The results suggest that the
      severity of atherosclerosis may relate to cognitive decline in CADASIL and that
      this effect is possibly related to the degree of microstructural cerebral tissue
      lesions. Longitudinal studies are needed to confirm these results.

PMID- 21178350
TI  - Protocol and methodology of the Stroke in Young Fabry Patients (sifap1) study: a
      prospective multicenter European study of 5,024 young stroke patients aged 18-55
      years.
AB  - BACKGROUND: Stroke in the young has not been thoroughly investigated with most
      previous studies based on a small number of patients from single centers.
      Furthermore, recent reports indicate that Fabry disease may be a significant
      cause for young stroke. The primary aim of our study was to determine the
      prevalence of Fabry disease in young stroke patients, while the secondary aim was
      to describe patterns of stroke in young patients. METHODS: We initiated the
      Stroke in Young Fabry Patients (sifap1) study as a multinational prospective
      European study of stroke patients aged 18-55 years and collected a broad range of
      clinical, laboratory, and radiological data using stringent standardized methods.
      All patients were tested for Fabry disease and blood was stored for future
      genetic testing. RESULTS: We managed to enroll 5,024 eligible young stroke
      patients in 15 countries and 47 centers across Europe between April 2007 and
      January 2010. The median number of patients included per center was 98 with a
      range between 8 and 315. The average duration of patient recruitment per center
      was 22 months, ranging between 5 and 33 months. The database was closed in July
      2010. This paper describes protocol and methodology of the sifap1 study.
      CONCLUSION: The sifap1 study included the largest series of young stroke patients
      so far and will allow for analyses on a large number of aspects of stroke in the
      young.

PMID- 21178351
TI  - Evolution of atherosclerotic carotid plaque morphology: do ulcerated plaques
      heal? A serial multidetector CT angiography study.
AB  - BACKGROUND: Atherosclerotic carotid plaque rupture may lead to
      thromboembolization, causing transient ischemic attack or ischemic stroke.
      Carotid plaque ulceration on angiography is associated with plaque rupture.
      Although healing of ruptured plaques has been described in coronary arteries,
      little is known about the natural development of plaque ulcerations in carotid
      arteries. We therefore explored the evolution of carotid plaque surface
      morphology with serial multidetector CT angiography (MDCTA). METHODS: From a
      registry of patients with transient ischemic attack or minor ischemic stroke, we
      selected 83 patients who had undergone serial MDCTA of the carotid arteries.
      Arteries subjected to revascularization procedures between the two scans were
      excluded (n = 11). Plaque surface morphology was classified as smooth, irregular
      or ulcerated on both baseline and follow-up MDCTA. Progression (i.e. development
      of irregularities or ulceration) and regression (i.e. disappearance of
      irregularities or ulceration) in morphology were evaluated. RESULTS: The mean
      time interval between the MDCTA scans was 21 +/- 13 months. At baseline, 28 (18%)
      arteries were normal, 124 (80%) contained atherosclerotic plaque and 3 (2%) were
      occluded. Plaque surface morphology was smooth in 86 arteries (55%), irregular in
      23 (15%) and ulcerated in 15 (10%). At follow-up, surface morphology was
      unchanged in 88% of arteries, had progressed in 8% and regressed in 4%. Most
      importantly, plaque morphology remained unchanged in most ulcerated plaques
      (10/15; 67%). One ulcerated plaque had progressed, whereas 4 had regressed. New
      ulcerations had developed in 2 nonulcerated plaques. CONCLUSION: MDCTA allows
      evaluation of temporal changes in atherosclerotic carotid plaque morphology.
      Plaque surface morphology remained unchanged in most arteries. Carotid
      ulcerations persist for a long time, and may remain a potential source of
      thromboembolism.

PMID- 21178352
TI  - Chronic kidney disease in patients with acute intracerebral hemorrhage:
      association with large hematoma volume and poor outcome.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with both a risk of
      adverse vascular outcome and a risk of bleeding. We have tested the hypothesis
      that in the setting of an acute intracerebral hemorrhage (ICH), CKD is associated
      with poor outcome and with larger hematoma volume. METHODS: We examined the
      association between CKD and ICH characteristics and outcome within a prospective
      cohort study of consecutive patients hospitalized with an acute stroke and
      followed for 1 year. CKD was categorized by the estimated baseline glomerular
      filtration rate into moderate/severe impairment (<45), mild impairment (45-60)
      and no impairment (>60 ml/min/1.73 m(2)). RESULTS: Among 128 patients with an ICH
      (mean age = 71.7 +/- 12.3 years, 41.4% women) 46.1% had CKD (23.4% mild and 22.7%
      moderate/severe). Patients with moderate/severe impairment had >4-fold adjusted
      hazard ratio for mortality over 1 year (4.29; 95% CI = 1.69-10.90) compared to
      patients with no impairment. The hematoma volumes [median (25-75%)] were 15.3 ml
      (5.4-37.5) in patients with no impairment, 16.6 (6.8-36.9) in mild impairment and
      50.2 (10.4-109.1) in moderate/severe impairment (p = 0.009). The location of the
      hematoma was lobar in 12% with no impairment, 17% with mild impairment and 39%
      with moderate/severe impairment (p = 0.02). Patients with moderate/severe
      impairment exhibited a 2.3-fold higher hematoma volume (p = 0.04) and a >6-fold
      higher odds of lobar location (95% CI = 1.59-24.02) as compared to no impairment.
      Further adjustment for antiplatelet use and for presence of leukoaraiosis
      attenuated the association with hematoma volume (p = 0.15), while moderate/severe
      impairment was associated with an adjusted OR of 5.35 (95% CI = 1.18-24.14) for
      lobar location. CONCLUSIONS: Presence of moderate/severe CKD among patients with
      ICH is associated with larger, lobar hematomas and with poor outcome.

PMID- 21178353
TI  - Rapid neurological recovery after intravenous tissue plasminogen activator in
      stroke: prognostic factors and outcome.
AB  - BACKGROUND: Treatment with tissue plasminogen activator (tPA) is associated with
      improved outcome in acute ischemic stroke. Of note, a proportion of patients
      demonstrate rapid and significant neurological recovery within 24 h. This has
      previously not been systematically studied. We aimed to examine its incidence,
      predictive factors and correlation with clinical outcomes. METHODS: We included
      161 patients with acute ischemic stroke who received intravenous tPA within 4.5
      h. Patient demographics and clinical data were collected. Rapid neurological
      recovery was defined as an improvement of at least 50% within 24 h as measured by
      the National Institute of Health Stroke Scale (NIHSS) score, and long-term
      outcomes were assessed by 3-month modified Rankin Scale. The incidence of rapid
      neurological recovery and its correlation with outcomes were studied. The
      predictors of the phenomenon were examined by univariate analysis. RESULTS: Rapid
      neurological recovery was present in 44 of the 161 patients (27.3%). This
      correlated with favorable outcomes at 3 months (p < 0.0005). Lower baseline NIHSS
      score (p = 0.006), mild (NIHSS score <12) versus severe stroke (NIHSS score >=12;
      p = 0.002), normal serum glucose levels on admission (3.3-7.7 mmol/l; p = 0.009)
      and younger age (p = 0.043) predicted rapid neurological recovery. However, there
      was no association with time to treatment (p = 0.3). CONCLUSION: Rapid
      neurological recovery defines a rapid responder population and was demonstrated
      in a quarter of patients treated with intravenous tPA. It strongly predicts a
      good clinical outcome.

PMID- 21178354
TI  - Chromosomal homologies among vampire bats revealed by chromosome painting
      (phyllostomidae, chiroptera).
AB  - Substantial effort has been made to elucidate karyotypic evolution of
      phyllostomid bats, mostly through comparisons of G-banding patterns. However, due
      to the limited number of G-bands in respective karyotypes and to the similarity
      of non-homologous bands, an accurate evolutionary history of chromosome segments
      remains questionable. This is the case for vampire bats (Desmodontinae). Despite
      several proposed homologies, banding data have not yet provided a detailed
      understanding of the chromosomal changes within vampire genera. We examined
      karyotype differentiation of the 3 species within this subfamily using whole
      chromosomal probes from Phyllostomus hastatus (Phyllostominae) and Carollia
      brevicauda (Carolliinae). Painting probes of P. hastatus respectively detected
      22, 21 and 23 conserved segments in Diphylla ecaudata, Diaemus youngi, and
      Desmodus rotundus karyotypes, whereas 27, 27 and 28 were respectively
      detectedwith C. brevicauda paints. Based on the evolutionary relationships
      proposed by morphological and molecular data, we present probable chromosomal
      synapomorphies for vampire bats and propose chromosomes that were present in the
      common ancestor of the 5 genera analyzed. Karyotype comparisons allowed us to
      relate a number of conserved chromosomal segments among the 5 species, providing
      a broader database for understanding karyotype evolution in the family.

PMID- 21178355
TI  - Effect of psychiatric severity on the outcome of methadone maintenance treatment.
AB  - While psychiatric comorbidity has been shown to produce a negative impact on the
      outcome of opioid use disorders, longitudinal studies carried out in the context
      of methadone maintenance treatment programs (MMTP) to evaluate outcomes strictly
      linked to methadone efficacy have not demonstrated a similar negative influence.
      To verify whether results obtained considering psychopathology in terms of formal
      psychiatric diagnoses were replicated when assessing psychopathology in terms of
      global psychiatric severity, a retrospective cohort study was designed. 259
      patients commencing methadone maintenance treatment were divided into two groups
      on the basis of SCL-90 severity score and compared for retention in treatment,
      toxicological urine test results and psychological/psychiatric status throughout
      a one year period of observation. The results of the study suggest that patients
      in MMTP with high psychiatric severity are not characterized by a lower retention
      in treatment or higher substance use than those with low psychiatric severity.
      Moreover, during treatment high severe psychiatric patient status appears to
      improve significantly for all psychological/psychiatric dimensions explored by
      SCL-90. These results are consistent with those obtained in previous studies on
      the efficacy of MMTP, comprehensive of psychiatric care, irrespective of the
      severity of psychopathology exhibited by patients at the beginning of treatment.

PMID- 21178356
TI  - Alcohol habits in Sweden during 1997-2009 with particular focus on 2005 and 2009,
      assessed with the AUDIT: a repeated cross-sectional study.
AB  - AIM: This study aimed to survey the changes in alcohol habits during a period
      with the European Union legal practices. METHODS: Alcohol habits in Sweden were
      surveyed in the general Swedish population at four timepoints, in 1997, 2001,
      2005 and 2009, using the 10-item AUDIT questionnaire. DESIGN: Four separate
      randomly drawn cross-sectional samples of 1,250 individuals were surveyed at each
      timepoint. RESULTS: An average of 70% of the sampled individuals responded to the
      AUDIT questionnaire. Men had higher total AUDIT scores than women in 2005 and
      2009, but scores increased among women 61-71 years old and decreased among men 61
      71 years old. Younger men and women 17-27 years old decreased their AUDIT-C
      consumption scores by almost 20% between 2005 and 2009. An analysis of problem
      drinkers (+8 for men/+6 for women) indicated that a larger proportion of elderly
      women drank moderately in 2009 compared with 2005, but fewer elderly women drank
      hazardously. CONCLUSIONS: Earlier increases in drinking levels between 1997 and
      2001 may reflect a latent high demand that was restricted by low availability.
      When availability due to European Union harmonization increased, alcohol
      consumption followed suit. After a period of adaptation, alcohol consumption
      appears to have stabilized.

PMID- 21178358
TI  - Human liver-specific nanocarrier in a novel mouse xenograft model bearing
      noncancerous human liver tissue.
AB  - For the targeted delivery of genes and drugs to the human liver, hepatitis B
      virus (HBV) envelope L particles, which form hollow nanoparticles and display a
      peptide that is indispensable for liver-specific infection by HBV in humans,
      should be a useful tool. To test the efficacy of these particles in vivo, in the
      present study we generated a small animal model harboring a functional human
      liver tissue xenograft. An anti-asialo GM1 antibody was administered to SCID mice
      to induce the depletion of natural-killer-cell-dependent immune responsibility
      and then the mice underwent transplantation of a noncancerous liver tissue
      originating in humans into the kidney capsule. Interestingly, human liver tissues
      were engrafted in 58% of the animals at least for 14 days shown by a human
      hepatocyte-specific antibody. The engineered HBV nanoparticles which contained
      fluorescent chemicals could selectively bind to the xenograft in these immune
      deficient mice when they were administered systemically. These results suggested
      that the model animal was usable to demonstrate the efficacy of the nanoparticles
      that could deliver chemicals specific to the normal human liver tissue by
      systemic administration, which will facilitate the study of human liver cell
      biology, drug metabolism and infections with hepatotropic viruses.

PMID- 21178362
TI  - Castration has antihypertensive and organoprotective effects in male but not in
      female heterozygous Ren-2 rats.
AB  - Gender differences in the regulation of blood pressure (BP) and the contributions
      of the renin-angiotensin system remain controversial. We assessed the effect of
      castration on BP and organ damage, as well as angiotensin II (ANG II), estradiol
      and testosterone levels in heterozygous Ren-2 transgenic (TGR) rats and transgene
      negative Hannover Sprague-Dawley control rats. Male TGR had severe hypertension
      throughout the experiment, while the BP of female TGR declined after 5 months to
      normotensive levels. Ovariectomy had no effect on BP, cardiac hypertrophy or
      proteinuria in female Ren-2 TGR. On the contrary, BP and cardiac hypertrophy were
      significantly reduced in castrated male TGR as compared to sham-operated TGR.
      Moreover, proteinuria in these animals was normalized to the levels of control
      rats. ANG II levels did not differ between male and female TGR, and no effect of
      castration on plasma and tissue ANG II levels was found either in male or female
      TGR at the end of the experiment. In conclusion, the contribution of the renin
      angiotensin system to the gender difference in BP homeostasis seems to be
      negligible in aging heterozygous Ren-2 transgenic rats.

PMID- 21178363
TI  - Functional analysis of the p40 and p75 proteins from Lactobacillus casei BL23.
AB  - The genomes of Lactobacillus casei/paracasei and Lactobacillus rhamnosus strains
      carry two genes encoding homologues of p40 and p75 from L. rhamnosus GG, two
      secreted proteins which display anti-apoptotic and cell protective effects on
      human intestinal epithelial cells. p40 and p75 carry cysteine, histidine
      dependent aminohydrolase/peptidase (CHAP) and NLPC/P60 domains, respectively,
      which are characteristic of proteins with cell-wall hydrolase activity. In L.
      casei BL23 both proteins were secreted to the growth medium and were also located
      at the bacterial cell surface. The genes coding for both proteins were
      inactivated in this strain. Inactivation of LCABL_00230 (encoding p40) did not
      result in a significant difference in phenotype, whereas a mutation in
      LCABL_02770 (encoding p75) produced cells that formed very long chains. Purified
      glutathione-S-transferase (GST)-p40 and -p75 fusion proteins were able to
      hydrolyze the muropeptides from L. casei cell walls. Both fusions bound to mucin,
      collagen and to intestinal epithelial cells and, similar to L. rhamnosus GG p40,
      stimulated epidermal growth factor receptor phosphorylation in mouse intestine ex
      vivo. These results indicate that extracellular proteins belonging to the
      machinery of cell-wall metabolism in the closely related L. casei/paracasei-L.
      rhamnosus group are most likely involved in the probiotic effects described for
      these bacteria.

PMID- 21178364
TI  - Physiology of elite young male athletes.
AB  - Performance in sport takes place within a matrix of bio-cultural characteristics
      but boys' success in elite youth sport is underpinned by a range of age-and
      maturity-related physical and physiological variables which act in a sport
      specific manner to influence performance. Stature, body mass, and muscle mass
      increase with growth and maturation and earlier maturing boys are generally
      taller, heavier, and more muscular than boys of the same chronological age who
      mature later. Earlier maturing boys also benefit from changes in body shape which
      are advantageous in many sports. Marked increases in muscle strength and muscle
      power are expressed during adolescence. The muscle enzyme profile needed to
      promote the anaerobic generation of energy is enhanced as children move through
      adolescence into young adulthood. Aerobic fitness benefits from age and/or
      maturation-related increases in stroke volume, haemoglobin concentration, and
      muscle mass. These individual differences are most pronounced at 12-15 years when
      participation in elite youth sport is at its peak. Many boys fulfil their
      potential, gain great pleasure from elite youth sport and become elite adult
      sportsmen. Other equally talented boys are denied access to elite youth sport
      through selection policies which are influenced by stage of maturation or age
      relative to the beginning of the selection year. Others drop-out prematurely
      through early specialisation in a sport inappropriate for their late adolescent
      or adult physique. Boys are not mini-men and coaches and parents should focus on
      providing opportunities for all boys and on nurturing talent irrespective of the
      ticking of individual biological clocks.

PMID- 21178365
TI  - Physiology of elite young female athletes.
AB  - The participation of girls in elite sport has increased exponentially over the
      past 30 years. Despite these increases a tradition for recruiting boys for
      exercise studies persists and our knowledge of the physiologic response to
      exercise in girls remains limited. Girls' physiology varies with age and
      maturation and is underpinned by a divergent hormonal milieu which begins early
      in foetal life. Sexual dimorphism underlies much of the physiologic response to
      exercise, and becomes most acute during adolescence when boys become taller,
      heavier, less fat and are more muscular than girls. Young girl athletes are not
      simply smaller, less muscular boys. The widening sex disparity in responses to
      exercise during puberty cannot always be accounted for by size. The woeful number
      of studies on girls and our prior inability to non-invasively study the
      complexity of the cellular metabolic response to exercise means an integrative
      understanding of girls' physiological responses to exercise remains elusive.
      Success in elite sport requires intense training, which for a long time was
      thought to cause disruption to normal growth and maturation. It would appear that
      exercise training, without other predisposing factors, is unlikely to cause
      aberrations to either growth or maturation. Nevertheless, there is clear evidence
      of a boundary between healthy and unhealthy levels of exertion when coupled with
      caloric limitation. Sports in which intense training is combined with the need
      for leanness may predispose girls to increased risk of skeletal and reproductive
      health problems, and ensuring risk is minimised should be a priority.

PMID- 21178366
TI  - Nutrition and elite young athletes.
AB  - Nutrition can play an essential role in the health of elite young athletes as
      well as exercise performance. Children and adolescents need adequate energy
      intake to ensure proper growth, development, and maturation. In addition, the
      requirements may further increase with increasing exercise training. There are,
      however, several metabolic differences that result in slightly different advice
      for young versus adult athletes. For example, younger athletes generally rely
      more on fat as a fuel, have smaller glycogen stores and have a limited glycolytic
      capacity. This would imply reduced carbohydrate requirements but a greater
      capacity to oxidize fat. There are also differences in thermoregulation, although
      the exact impact on fluid requirements is not clear. The limited evidence
      suggests that acute energy and fluid imbalances can be detrimental to performance
      and there may be benefits of ingesting carbohydrate and fluid during exercise,
      especially during more prolonged exercise. Exogenous carbohydrate oxidation rates
      have been reported to contribute more to energy expenditure in children. This
      may, however, simply be a reflection of the fact that the oxidation of this
      carbohydrate is not limited by body size, but by absorption. Absorption rates are
      likely to be similar in children and adults and therefore exogenous carbohydrate
      oxidation rates should be comparable. The relative contribution will therefore be
      higher because of the lower absolute intensities in children. There are a large
      number of questions still unanswered and sports nutrition advice to the elite
      young athlete is largely extrapolated from the adult population. Therefore, more
      research is needed in the years to come to give better advice to these young
      athletes.

PMID- 21178367
TI  - Endurance training and elite young athletes.
AB  - Endurance training consists of a structured exercise programme that is sustained
      for a sufficient length of time with sufficient intensity and frequency to induce
      an improvement in aerobic fitness. Elite young athletes generally have higher
      peak oxygen uptakes (peak VO2) than their untrained peers largely due to their
      greater maximal stroke volumes. Trained young athletes have faster VO2 kinetic
      responses to step changes in exercise intensity but whether this is due to
      enhanced oxygen delivery or increased oxygen utilization by the muscles remains
      to be explored. Blood lactate accumulation in young athletes during submaximal
      exercise is lower than in untrained youth and this appears to be due to enhanced
      oxidative function in the active muscles. No well-designed, longitudinal
      endurance training studies of elite young athletes have been published. Even in
      the general paediatric population peak VO2 is the only component of aerobic
      fitness on which there are sufficient data to examine dose-response effects of
      endurance training. The existence of a maturational threshold below which
      children are not trainable remains to be proven. The magnitude of training
      responses is independent of sex. Pre-training peak VO2 has a moderate but
      significant inverse relationship with post-training peak VO2 which suggests that
      elite young athletes are likely to experience smaller increases in peak VO2 with
      further endurance training than untrained youth. Empirical evidence strongly
      indicates that both trained and untrained young people can benefit from endurance
      training but the relative intensity of exercise required for optimum benefits is
      higher than that recommended for adults.

PMID- 21178368
TI  - High-intensity and resistance training and elite young athletes.
AB  - Although in the past resistance and high-intensity exercise training among young
      children was the subject of numerous controversies, it is now well-documented
      that this training mode is a safe and effective means of developing maximal
      strength, maximal power output and athletic performance in youth, provided that
      exercises are performed with appropriate supervision and precautions. Muscular
      strength and power output values measured from vertical jump and Wingate
      anaerobic tests are higher in elite than in non-elite young athletes and normal
      children, and the specific training effects on maximal power output normalised
      for body size are clearly more distinct before puberty. At present, there is no
      scientific evidence to support the view that high-intensity and/or resistance
      training might hinder growth and maturation in young children. Pre-pubertal
      growth is not adversely affected by sport at a competitive level and
      anthropometric factors are of importance for choice of sport in children.
      However, coaches, teachers and parents should be aware that unsupervised high
      intensity and resistance training programmes involving maximal loads or too
      frequently repeated resistance exercises increase the risk of injury. Resistance
      training alone is an effective additional means of developing athletic
      performance throughout planned youth sports training programmes. Strategies for
      enhancing the effectiveness and safety of youth resistance and high-intensity
      exercise training are discussed in this chapter.

PMID- 21178369
TI  - Overtraining and elite young athletes.
AB  - In comparison to adults, our knowledge of the overtraining syndrome in elite
      young athletes is lacking. The evidence indicates an incidence rate of ~20-30%,
      with a relatively higher occurrence seen in individual sport athletes, females
      and those competing at the highest representative levels. The most commonly
      reported symptoms are similar to those observed in over trained adult athletes:
      increased perception of effort during exercise, frequent upper respiratory tract
      infections, muscle soreness, sleep disturbances, loss of appetite, mood
      disturbances, shortness of temper, decreased interest in training and
      competition, decreased self-confidence, inability to concentrate. The association
      between training load and overtraining is unclear, and underlines the importance
      of taking a holistic approach when trying to treat or prevent overtraining in the
      young athlete so that both training and non-training stressors are considered. Of
      particular relevance to the issue of overtraining in the elite young athlete are
      the development of a unidimensional identity, the lack of autonomy,
      disempowerment, perfectionist traits, conditional love, and unrealistic
      expectations. Overtraining syndrome is a complex phenomenon with unique and
      multiple antecedents for each individual; therefore, an open-minded and
      comprehensive perspective is needed to successfully treat/prevent this in the
      young athlete.

PMID- 21178370
TI  - Exercise testing elite young athletes.
AB  - Children and adolescents are becoming increasingly involved in competitive sport
      and, as a consequence, are engaging in specialized training with the objective of
      enhancing their sporting performance. An important aspect of achieving this goal
      is to ensure young athletes receive appropriate and on-going physiological
      assessment and support. Moreover, as young athletes require unique consideration
      (e.g. impact of biological maturity) compared to senior athletes, the challenge
      is for the exercise physiologist to adopt appropriate methods of assessment. This
      paper reviews field-and laboratory-based assessment of young athletes' aerobic
      fitness and performance during maximal intensity exercise. However, as studies of
      elite young athletes in their sporting environment are limited, the extant sport
      literature is complemented with data from untrained young people. The most
      appropriate variables to measure, which methodology and protocol to use, and how
      best to interpret the results of relevant tests are addressed. Key measurement
      issues relating to the specificity, validity and reliability of the physiological
      measures are examined and where possible, sport-specific measures are presented.
      The unique issues and considerations of providing continued physiological support
      to young athletes are discussed.

PMID- 21178371
TI  - Temperature regulation and elite young athletes.
AB  - Children and adults employ different thermoregulatory strategies, particularly in
      dealing with heat stress. Children rely more on 'dry' heat exchange, while
      evaporative heat loss is adults' foremost heat-dissipation venue. Several
      anatomical, physiological, and psychological factors can affect differential risk
      of thermal injury in the child vs. the adult athlete, in some situations.
      Children have greater surface-area- to-mass ratio, lower sweating rate, higher
      peripheral blood flow in the heat, and a greater extent of vasoconstriction in
      the cold. They can acclimatise to a similar extent but do so at a lower rate than
      adults. Differences in perceived exertion and thermal strain, cumulative
      experience, cognitive development, and decision-making capacity may negatively
      affect the young athlete's behaviour under competitive and other situations,
      possibly subjecting him/her to sub-par performance or to greater risk of thermal
      injury. However, except for very limited environmental conditions, children in
      general, and young athletes in particular, are physiologically as capable as
      adults to handle environmental challenges.

PMID- 21178372
TI  - Environmental factors affecting elite young athletes.
AB  - To date, much of the research concerning the performance of elite young athletes
      has focused on physical and physiological factors and how these relate to age and
      maturation. Little attention has been paid to other factors which might limit
      performance such as nutrition or environmental stressors. The paucity of research
      on the environmental effects on performance in young athletes is unsurprising
      given the need for experimental studies, the ethics of which would generally be
      untenable. As an outcome, there is a reliance on observational and case study
      data, e.g. observing the stressors which occur during jet lag and effects on
      sleep patterns, altitude and pollution. The effects of environmental factors have
      been predominantly researched from a health context in youngsters rather than a
      performance context. However, the evidence of those few empirical studies
      combined with coach and/or sports science support teams' experience have provided
      professionals with some guidelines. These applied guidelines include sleep
      patterns, jet lag, pollution and altitude research, to aid those preparing young
      athletes for training and competition in environments that present potential
      challenges to performance. The limitations of data extrapolated from adults are
      acknowledged and in all cases it is emphasised that recommendations and
      implementing practice should be based on data collected from young people.

PMID- 21178373
TI  - Prevention of sudden cardiac death in young athletes: controversies and
      conundrums.
AB  - Strategies for preventing sudden cardiac death in young athletes are predicated
      on the assumption that: (1) these events reflect pre-existing, clinically silent
      heart disease, and (2) means for detecting these abnormalities on the pre
      participation evaluation are both feasible and accurate. Recent controversy has
      surrounded both of these presumptions. Some evidence suggests that the myocardial
      hypertrophy accompanying sports training itself might serve as a substrate for
      fatal arrhythmias. As well, vigorous debate has arisen over the optimal content
      of the pre-participation evaluation, particularly regarding the inclusion of
      routine screening electrocardiograms. As the rarity of these fatal events does
      not lend itself to an experimental approach, such disagreements are not easily
      resolved. Consequently, it is expected that decisions regarding approaches to
      prevention of sudden death in athletes will be dictated largely by region
      specific financial, political, and cultural factors. This chapter examines the
      aetiologies of sudden cardiac death in young athletes as well as the
      controversies surrounding the prevention of these tragedies.

PMID- 21178374
TI  - Aetiology and prevention of injuries in elite young athletes.
AB  - Sport participation confers many varied benefits in children and adolescents,
      such as self-esteem, confidence, team play, fitness, agility and strength.
      Nevertheless, the age of initiation of intense training is decreasing and
      programmes which expose children to excessive amounts of exercise increase the
      risk of injury. We review sports injuries in young athletes and the long-term
      outcomes. Sports injuries can lead to disturbances in growth such as limb length
      discrepancy, caused by traumatised physeal growth induced by injury. Osgood
      Schlatter lesion may also cause some sequelae such as painful ossicles in the
      distal patellar tendon. The apophysis can be fragmentised or separated, and this
      could be an adaptive change to the increased stress typical of overuse
      activities. These changes produce an osseous reaction even though they are not
      disabling. Participation in physical exercise at a young age should be
      encouraged, because of the health benefits, but decreasing the incidence and
      severity of sports injuries in young athletes is an important component of any
      athletic programme and may generate a long-term economic impact in health care
      costs. Active prevention measures are the main weapon to decrease the (re-)injury
      rate and to increase athletic performance.

PMID- 21178375
TI  - Intravenous iron therapy and risk for progressive loss of kidney function in
      patients with chronic kidney disease.
AB  - BACKGROUND: Intravenous (IV) iron is used in the treatment of anemia in patients
      with chronic kidney disease (CKD). Several lines of evidence have brought up
      potential concerns regarding the effect of IV iron on the kidney, specifically
      the possibility of IV iron leading to renal injury and hastening the progression
      of CKD. METHODS: We performed a retrospective analysis of 77 patients to assess
      the rate of change in kidney function prior to and after IV iron infusion.
      RESULTS: Patients were followed for an average of 21.3 months (range 2-35) prior
      and 32.8 months (range 2-58) after the single iron infusion. Sixty-one percent of
      patients had CKD stage 3 and 30% were at CKD stage IV at the time of iron
      infusion. Of the 77 patients, 74.1% received iron dextran and 25.9% received
      ferric gluconate (1 g total). The average slope before and after iron infusion
      for 1/serum creatinine versus time (months) were -0.0066 and -0.0053,
      respectively (p = 0.12). The average slope before and after iron infusion for
      glomerular filtration rate versus time (months) were -0.5439 and -0.2998,
      respectively (p = 0.14). There was no difference in subgroup analysis in the rate
      of change in renal function in those with more advanced renal function as opposed
      to those with more preserved renal function. CONCLUSION: In this limited
      retrospective study, IV iron dextran or ferric gluconate was not associated with
      a change in the rate of progression of CKD.

PMID- 21178376
TI  - Renal function in patients with liver cirrhosis.
AB  - BACKGROUND: Despite the poor prognosis of patients with both cirrhosis and renal
      failure, most reports on renal function and outcomes of cirrhosis have come from
      liver transplant registries. The present study aimed to investigate the
      association between renal function and cirrhosis in a broader population.
      METHODS: 3,857 patients were enrolled after the exclusion of patients with
      incomplete data. The most recent demographic data after the latest laboratory
      measurements obtained at outpatient or inpatient department were collected.
      RESULTS: In predicting renal function, estimated glomerular filtration rate
      (eGFR) was found to be dissociated from Child-Pugh points (beta = -0.01, p =
      0.691), different causes of cirrhosis, and presence of diabetes (beta = -0.03, p
      = 0.112). In terms of predicting in-hospital mortality, the sensitivity (60-82%)
      and specificity (70-90%) of the model for end-stage liver disease (MELD) score
      increased with the decrease in eGFR. However, the blood urea nitrogen
      (BUN)/creatinine ratio was better than the MELD score in patients with normal
      eGFR. CONCLUSION: In contrast to prerenal causes of kidney injury, the underlying
      causes of cirrhosis or diabetes had relatively minor effects on renal function in
      cirrhotic patients. The BUN/creatinine ratio was a better index than the MELD
      score in predicting in-hospital mortality in cirrhotic patients with normal renal
      function.

PMID- 21178377
TI  - Impact of hypovitaminosis D and alfacalcidol therapy on survival of hemodialysis
      patients: results from the French ARNOS study.
AB  - BACKGROUND: In chronic kidney disease and dialysis patients, vitamin D deficiency
      is associated with mortality. In some observational studies, calcitriol analogue
      therapy was associated with a better survival rate in hemodialysis (HD) patients.
      The aim of this study was to determine the relationship between serum 25
      hydroxyvitamin D (25-OHD) levels and alfacalcidol therapy with HD patients'
      outcomes. METHODS: We measured baseline 25-OHD levels using a cross-sectional
      analysis in 648 HD prevalent patients from the regional ARNOS French cohort. A 42
      month survival analysis was applied according to serum 25-OHD level and
      calcitriol analogue therapy. RESULTS: The prevalence of 25-OHD insufficiency <30
      ng/ml was high (73%), with only 22% taking native vitamin D supplementation. A
      baseline 25-OHD level above the median value (18 ng/ml) was associated with lower
      all-cause mortality [hazard ratio (HR), 0.73 (0.5-0.96); p = 0.02] after
      adjustment for age, gender, dialysis vintage, calcemia, phosphatemia,
      cardiovascular disease, and diabetes. Only in monovariate analysis was low-dose
      oral alfacalcidol therapy associated with a better survival rate in patients with
      and without 25-OHD deficiency [HR, 0.7 (0.5-0.92); p = 0.05]. CONCLUSIONS: Our
      study shows that, among prevalent HD patients, low 25-OHD levels affect
      mortality. Alfacalcidol therapy, especially in small doses, may provide
      compensation, but this needs to be further confirmed using prospective controlled
      studies comparing native and active vitamin D compounds.

PMID- 21178378
TI  - Association between very low PTH levels and poor survival rates in haemodialysis
      patients: results from the French ARNOS cohort.
AB  - INTRODUCTION: A very low parathyroid hormone (PTH) level (VLPL) is associated
      with an increased risk of adynamic bone disease, vascular calcification, and
      mortality in haemodialysis (HD) patients. The aim of the study was to assess the
      frequency, the associated factors, and the prognosis of non-surgical VLPL in a
      cohort of prevalent HD patients. METHODS: In July 2005, a cross-sectional study
      was performed on the French ARNOS cohort in 1,348 prevalent HD patients from 24
      dialysis centres in the Rhone-Alpes area. Patients with a baseline intact PTH
      level <50 pg/ml (VLPL, Group 1) and >= 50 pg/ml (Group 2) were compared and a 42
      month survival analysis was performed. Patients with prevalent or incident
      parathyroidectomy were excluded. RESULTS: We studied 1,138 prevalent HD patients.
      As compared to patients of Group 2 (n = 1,019), patients with VLPL (Group 1, n =
      119) had lower serum albumin levels (34.5 +/- 5 vs. 36.4 +/- 5 g/l, p < 0.0001),
      less protein intake (nPCR 0.99 +/- 0.28 vs. 1.1 +/- 0.28 g/kg/day, p = 0.01),
      higher calcaemia (2.30 +/- 0.2 vs. 2.26 +/- 0.2 mmol/l, p = 0.01) and were more
      frequently treated with calcium carbonate (67 vs. 54%, p < 0.001). Patients with
      VLPL had a higher mortality rate (HR: 1.4 (1.07-1.8), p = 0.006) after adjustment
      for age, gender, diabetes, and dialysis vintage. The odds ratios of mortality for
      patients with VLPL remained higher in all calcaemia and serum albumin quartiles.
      Only 3/119 patients in Group 1 did not receive any PTH-lowering therapies (i.e.
      calcium carbonate (67%), alfacalcidol (38%), cinacalcet (10.1%), and dialysate
      calcium >= 1.5 mmol/l (94%)). CONCLUSION: In this observational French cohort,
      VLPL was observed in 10% of prevalent HD patients and was associated with poor
      survival rates. An inadequate therapeutic strategy could be responsible for this
      observation. The real consequences of this iatrogenic adynamic bone disease
      remain hypothetical, but it may be related to the risk of developing vascular
      calcification. It is hypothesized that a more adequate strategy, using fewer PTH
      lowering therapies in cases of VLPL, may help in improving the poor prognosis.

PMID- 21178379
TI  - Hemodynamic changes in the prefrontal cortex during digit span task: a near
      infrared spectroscopy study.
AB  - BACKGROUND/AIMS: In this study, we examined changes in the concentrations of
      oxygenated and deoxygenated hemoglobin (oxy- and deoxy-Hb, respectively) in the
      prefrontal cortex (PFC) during the digit span task by using near-infrared
      spectroscopy (NIRS). METHODS: The digit span task consists of the digit span
      forward and backward tasks. The tasks were performed by 22 healthy undergraduate
      students who participated in this study. Differences in the mean concentrations
      of oxy-Hb and deoxy-Hb between the baseline and task intervals were evaluated.
      RESULTS: In digit span backward, oxy-Hb was significantly higher during the task
      interval than during the baseline. Further, deoxy-Hb was significantly lower
      during the task interval than during the baseline in both digit span forward and
      digit span backward. Digit span forward performance was significantly higher for
      the right-PFC-dominant group than for the left-PFC-dominant group. CONCLUSION:
      These results suggest that the digit span backward task is more demanding and
      requires greater activation of the prefrontal cortex than the digit span forward
      task. Our NIRS findings suggest that the digit span backward task involves
      executive functioning.

PMID- 21178380
TI  - Altered frontal and temporal brain function during olfactory stimulation in adult
      attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: Olfactory processing depends on dopamine metabolism and orbitofrontal
      cortex functioning, both known to be disturbed in attention-deficit/hyperactivity
      disorder (ADHD). Some investigations suggested alterations in olfactory
      processing (identification and sensitivity) in childhood and adult ADHD. METHODS:
      In the present study we investigated olfactory function (Sniffin' Sticks) of 29
      adult patients with ADHD (17 combined, 11 inattentive, and 1
      hyperactive/impulsive subtype) and 29 controls matched for sex, handedness, age,
      intelligence, and education. Additionally, we measured frontal, temporal, and
      somatosensory cortical activity during olfactory perception. This was performed
      with functional near-infrared spectroscopy (fNIRS) during presentation of 2
      phenylethanol (olfactory stimulant) and linalool (mixed olfactory/trigeminal
      stimulant) in two concentrations each. RESULTS: Adult patients with ADHD and
      controls did not differ in sensitivity for and discrimination and identification
      of olfactory stimuli. Functional brain imaging measures with fNIRS generally
      revealed diminished activation in olfaction-associated brain regions in patients
      with ADHD. Only for a high concentration of linalool, oxygenated haemoglobin
      (O2Hb) concentrations in patients were similar to controls (significant increase
      in the temporal, somatosensory, and inferior-frontal cortex). O2Hb concentrations
      in active brain regions positively correlated with ADHD symptoms during childhood
      and trait impulsivity. These effects were carried for the subgroup with combined
      subtype. CONCLUSIONS: Although we could not replicate altered clinical
      performance in ADHD, our fNIRS findings suggest an association of cortical
      olfactory processing with hyperactivity and impulsivity in adult ADHD.

PMID- 21178381
TI  - Prolactin and cortisol responses to acute intravenous clomipramine challenge in
      patients with mania, depression and healthy controls: evidence for reduced
      serotonergic responsivity.
AB  - Serotonergic dysregulation has been shown to be involved in the pathophysiology
      of unipolar and bipolar depression. Neuroendocrine challenge tests have been
      extensively used to investigate serotonin functioning in the brain. Although the
      role of serotonin has received a great deal of attention using neuroendocrine
      challenge paradigms, little effort has been made to explore the role of serotonin
      in mania. We assessed serotonergic neuroendocrine responsivity in patients with
      depression (n = 22), mania (n = 11) and 15 healthy controls by measuring the
      prolactin (PRL) and cortisol responses to i.v. clomipramine (CMI) and searched
      for possible differences among the groups. Blunted PRL responses to CMI in manic
      and depressed patients compared to healthy controls were found. The response to
      CMI disclosed similar results for the 2 patient groups. No significant
      differences were found among the 3 subject groups in the cortisol response to
      CMI. The blunted PRL responses to CMI in patients with mania and depression
      suggest that serotonergic functioning in mania and depression is similarly
      impaired, at least at the level of hypothalamus-hypophysis.

PMID- 21178382
TI  - Autonomic correlates at rest and during evoked attention in children with
      attention-deficit/hyperactivity disorder and effects of methylphenidate.
AB  - OBJECTIVE: The aim of this study was to assess autonomic nervous system
      functioning in children with attention-deficit/hyperactivity disorder (ADHD) and
      to examine the effects of methylphenidate and focussed attention. METHOD:
      Children with ADHD (n = 19) were tested while they were stimulant free and during
      a period in which they were on stimulants. On both occasions, autonomic nervous
      system functioning was tested at baseline and during focussed attention.
      Autonomic nervous system functioning of control subjects was also tested at
      baseline and during focussed attention. Autonomic nervous system activity was
      determined by means of heart rate variability (HRV) and skin conductivity
      analyses. Attention was evoked by means of the BioGraph Infiniti biofeedback
      apparatus. HRV was determined by time domain, frequency domain and Poincare
      analysis of RR interval data. Skin conductivity was determined by the BioGraph
      Infiniti biofeedback apparatus. RESULTS: The main findings of this study were (a)
      that stimulant-free children with ADHD showed a sympathetic underarousal and
      parasympathetic overarousal of the sympathovagal balance relative to control
      subjects; (b) methylphenidate shifted the autonomic balance of children with ADHD
      towards normal levels; however, a normal autonomic balance was not reached, and
      (c) stimulant-free children with ADHD exhibited a shift in the sympathovagal
      balance towards the sympathetic nervous system from baseline to focussed
      attention; however, methylphenidate appeared to abolish this shift. CONCLUSIONS:
      Stimulant-free children with ADHD have a parasympathetic dominance of the
      autonomic balance, relative to control subjects. Methylphenidate attempts to
      restore the normal autonomic balance in children with ADHD, but inhibits the
      normal autonomic nervous system response to a cognitive challenge. CLINICAL
      APPLICATIONS: These results indicate that methylphenidate may have a suppressive
      effect on the normal stress response. Although this may be of benefit to those
      who interact with children who suffer from ADHD, the implications for the
      physiological and psychological well-being of the children themselves are
      debatable. Further research is needed. LIMITATIONS OF THE STUDY: Only 19 children
      with ADHD and 18 control subjects were tested. Further studies should include
      prior testing in order to exclude children with possible co-existing learning
      disabilities. Cognitive function and emotional responses of children with ADHD
      were not tested.

PMID- 21178383
TI  - Unfavorable polysomnographic sleep patterns predict poor sleep and poor
      psychological functioning 3 years later in patients with restless legs syndrome.
AB  - BACKGROUND: Amongst the variety of disorders affecting sleep, restless legs
      syndrome (RLS) merits particular attention. Little is known about long-term
      outcomes for sleep or psychological functioning following a diagnosis of RLS. The
      aim of the present study was thus to evaluate sleep and psychological functioning
      at a 3-year follow-up and based on polysomnographic measurements. METHOD: Thirty
      eight patients (18 female and 20 male patients; mean age: 56.06, SD = 12.07) with
      RLS and sleep electroencephalographic recordings were followed-up 33 months
      later. Participants completed a series of self-rating questionnaires related to
      sleep and psychological functioning. Additionally, they completed a sleep log for
      7 consecutive days. RESULTS: Age, male gender, increased light sleep (S1, S2) and
      sleep onset latency, along with low sleep efficiency, predicted psychological
      functioning and sleep 33 months later. Specifically, sleep fragmentation
      predicted poor psychological functioning, and both sleep fragmentation and light
      sleep predicted poor sleep. CONCLUSIONS: In patients with RLS, irrespective of
      medication or duration of treatment, poor objective sleep patterns at diagnosis
      predicted both poor psychological functioning and poor sleep about 3 years after
      diagnosis. The pattern of results suggests the need for more thorough medical and
      psychotherapeutic treatment and monitoring of patients with RLS.

PMID- 21178384
TI  - Paroxetine rapidly modulates the expression of brain-derived neurotrophic factor
      mRNA and protein in a human glioblastoma-astrocytoma cell line.
AB  - Neuronal upregulation of the brain-derived neurotrophic factor (BDNF) gene
      appears to be a crucial factor for the efficacy of antidepressants. However,
      besides neurons, little information is present on the modulation of BDNF by
      antidepressants at RNA and protein levels in other cell types of the central
      nervous system. Glial cells are able to store and release BDNF, and it has been
      hypothesized that glial dysfunction may contribute to the etiopathogenesis of
      depression. Thus, in this study we used the human glioblastoma-astrocytoma cell
      line U87 exposed to the antidepressant drug paroxetine, and evaluated BDNF mRNA
      and protein expression. In addition, since the BDNF gene can be
      posttranscriptionally modulated by a family of microRNA, we also evaluated the
      levels for one of these microRNA (miR-30a-5p) in the U87 cell line during
      paroxetine treatment. We found that paroxetine treatment rapidly increased BDNF
      in U87 cells, resulting from an induction of BDNF mRNA expression and de novo
      protein synthesis, and that these increases occurred in a time-dependent manner.
      Paroxetine effects were evident at 6 h of incubation for BDNF mRNA and at 12 h
      for BDNF protein. In addition, the transcriptional BDNF inhibitor miR-30a-5p was
      also overexpressed at 6 and 12 h of paroxetine incubation. These findings
      indicate that the U87 cell line, an in vitro model of glial cells, rapidly
      responds to paroxetine by increasing BDNF production, and that these effects are
      potentially limited by microRNA induction. These data may contribute to explain
      the action of paroxetine on cells of nonneuronal origin.

PMID- 21178386
TI  - Acute and long-term efficacy and safety of sildenafil for the treatment of
      chronic thromboembolic pulmonary hypertension in a heart transplant recipient.
AB  - We report on the successful treatment with sildenafil of a unique case of severe
      chronic thromboembolic pulmonary hypertension which developed as a late
      complication in a 71-year-old heart transplant recipient, with focus on the
      potential therapeutic challenges encountered in the management of such a peculiar
      association of clinical conditions.

PMID- 21178385
TI  - Antisense inhibition of S6 kinase 1 produces improved glucose tolerance and is
      well tolerated for 4 weeks of treatment in rats.
AB  - p70 Ribosomal S6 kinase 1 (S6K1) is implicated in the pathogenesis of type 2
      diabetes as knockout mice are hypoinsulinemic, hypersensitive to insulin
      treatment and are less susceptible to obesity-induced insulin resistance.
      Although S6K1 knockout mice provide important information on the biology of this
      target, the therapeutic relevance of S6K1 inhibition in adult animals is unknown.
      Thus, this research evaluated the potential safety and efficacy of S6K1
      inhibition using antisense oligonucleotides (ASO) in mature Sprague-Dawley rats.
      Male rats treated with S6K1 ASO (25 or 50 mg/kg, 2*/week * 4 weeks) had a marked
      reduction (>90%) of S6K1 mRNA in the liver and epididymal fat and no effect on
      hepatic S6K2 expression. The decrease in S6K1 mRNA translated to decreased (>80%)
      S6K1 protein and kinase activity in the liver at the 50-mg/kg dose. The animals
      tolerated the S6K1 treatment well with no signs of clinical toxicity. A reduction
      in body weight gain was observed within 2 weeks of S6K1 ASO treatment. At 4
      weeks, body weight gain was reduced by up to 25% in the 50 mg/kg group with a
      commensurate decrease (14%) in food consumption. A decrease in heart weight in
      the 50 mg/kg group was observed and not associated with cardiac injury or
      dysfunction. In an oral glucose tolerance test, S6K1-ASO-treated animals
      demonstrated a dose-dependent improvement in systemic glucose utilization and had
      reduced fasting insulin levels. Hepatic gene microarray analysis identified dose
      dependent elevations in igfbp1, acss2 and acat2 gene expression in S6K1-ASO
      treated animals. These results suggest that inhibition of S6K1 for up to 4 weeks
      may be therapeutically relevant to induce insulin sensitization and attenuate
      weight gain with low risk for serious toxicity.

PMID- 21178387
TI  - Medical and economic interest of the use of cryosurgery in the instrumental
      treatment of atrial fibrillation.
AB  - INTRODUCTION: In order to definitively integrate cryosurgery for the surgical
      treatment of atrial fibrillation (AF) into the therapeutic armamentarium, the
      medical and economic impact of its use on a population of patients with a high
      risk of recurrence of postoperative AF must be evaluated. METHOD: An
      observational study of patients who benefited from cryosurgery between July 2006
      and December 2008 was performed. The cost of consumables and hospitalization was
      determined and compared to that of a control group of 27 patients with
      preoperative AF that had not benefited from cryosurgery. RESULTS: Twenty-nine
      patients benefited from cryosurgery during a mitral (65.5%) or aortic
      intervention (37.9%) to treat a paroxystic (44.8%) or permanent AF (55.2%). More
      than half of them (58.6%) had a 12-month follow-up; 82.4% of these patients
      showed a permanent sinus rhythm and 32.6% had stopped their antiarrhythmic
      medication. There was no significant difference between the duration and cost of
      hospitalization for the 2 groups. CONCLUSION: Cryosurgery provides a clear
      clinical and economic advantage with no recurrence of AF, and it reduces
      antiarrhythmic medication treatment.

PMID- 21178388
TI  - Progesterone rapidly attenuates ATP-evoked transient currents in cultured rat
      dorsal root ganglion neurons.
AB  - BACKGROUND: Progesterone has been shown to play a role in pain perception.
      However, the effects of progesterone on P2X3 receptors, the nociception-related
      receptors in primary sensory neurons, remain unclear. METHODS: We investigated
      the effects of progesterone on P2X3-receptor-mediated responses of rat dorsal
      root ganglion neurons by using whole-cell patch clamp techniques. RESULTS:
      Progesterone (10 pmol/l to 1 MUmol/l) inhibited ATP (100 MUmol/l)-induced
      transient currents and the transient component of biphasic currents in a dose
      dependent manner, but had no effect on the sustained currents. The effect of
      progesterone could be blocked by its receptor inhibitor, RU38486. Actidione, an
      inhibitor of protein synthesis, did not change the rapid effect. Investigations
      of the signaling pathways of progesterone showed that a nonselective antagonist
      of protein kinase, H-9, totally blocked the depressive effect of progesterone on
      ATP currents in a dose-dependent manner. Blocking protein kinase A with H-89 or
      KT5720 also affected progesterone-induced depression. The protein kinase A
      activator, forskolin, mimicked the effect of progesterone on ATP currents.
      CONCLUSION: These results suggest that progesterone may modulate pain signal
      transmission on dorsal root ganglia via regulating P2X3 receptor function. The
      cAMP-PKA signaling pathway is involved in the downregulating effect of
      progesterone on P2X3 receptors.

PMID- 21178389
TI  - Re: Paraneoplastic syndromes in patients with urological malignancies.

PMID- 21178390
TI  - Associations between DRDs and schizophrenia in a Korean population: multi-stage
      association analyses.
AB  - The dysregulation of the dopaminergic system has been implicated in the
      pathophysiology of major psychosis, including schizophrenia, with dopamine
      receptor genes (DRDs) presently targeted as the most promising candidate genes.
      We investigated DRD1-5 for association with schizophrenia using a multi-stage
      approach in a Korean sample. One hundred forty-two SNPs in DRD1-5 were selected
      from the dbSNP, and the associations of each SNP were then screened and typed by
      MALDI-TOF mass spectrometry using pooled DNA samples from 150 patients with major
      psychosis and 150 controls. Each of the suggested SNPs was then genotyped and
      tested for an association within the individual samples comprising each pool.
      Finally, the positively associated SNPs were genotyped in an extended sample of
      270 patients with schizophrenia and 350 controls. Among the 142 SNPs, 88 (62%)
      SNPs in our Korean population were polymorphic. At the pooling stage, 10 SNPs
      (DRD1: 2, DRD2: 3, and DRD4: 5) were identified (P<0.05). SNPs rs1799914 of DRD1
      (P=0.046) and rs752306 of DRD4 (P=0.017) had significantly different allele
      frequencies in the individually genotyped samples comprising the pool. In the
      final stage, with the extended sample, the suggestive association of DRD4 with
      rs752306 was lost, but the association of DRD1 with rs1799914 gained greater
      significance (P=0.017). In these large-scale multi-stage analyses, we were able
      to find a possible association between DRD1 and schizophrenia. These findings
      suggested the potential contribution of a multi-step strategy for finding genes
      related to schizophrenia.

PMID- 21178391
TI  - A case of anaplastic diffuse large B-cell thyroid lymphoma: unique
      immunophenotype and unusual clinical presentation.

PMID- 21178392
TI  - Endocrinology and Art. Painter in his studio, painting a musical company--Jan
      Miense Molenaer (1610-1668).

PMID- 21178394
TI  - First in humans: a new molecularly defined vaccine shows excellent safety and
      strong induction of long-lived Mycobacterium tuberculosis-specific Th1-cell like
      responses.
AB  - Tuberculosis (TB) remains a major killer worldwide. The only available TB
      vaccine, the nearly century-old Mycobacterium bovis BCG, has had only a limited
      effect on TB incidence. Therefore, developing new TB vaccines is a key priority,
      and the first new generation TB vaccines are now being tested in clinical trials.
      Here we describe the development and first testing in humans of a novel, wholly
      synthetic TB subunit vaccine. This vaccine has proven safe and highly immunogenic
      in all species in which it was tested, including mice, guinea pigs, non-human
      primates and humans. Most encouragingly, following vaccination in humans, strong
      IFN-gamma responses persisted through at least 21/2 years of follow-up,
      indicating induction of a substantial memory response by this new TB vaccine.
      These findings encourage further preclinical and clinical studies with TB subunit
      vaccines and cellular immunity-stimulating new adjuvants.

PMID- 21178393
TI  - Autophagy and cancer therapy.
AB  - Although autophagy has been shown to have a clear role as a tumor suppressor
      mechanism, its role in cancer treatment is still controversial. Because autophagy
      is a survival pathway activated during nutrient deprivation and other stresses,
      it is reasonable to think that autophagy can function as a tumor cell survival
      mechanism activated after cancer treatment. Such a mechanism could be widely
      important because most cancer treatments induce autophagy in tumor cells. Indeed,
      many papers have presented data suggesting that tumor cell autophagy induced by
      anti-cancer treatment inhibits tumor cell killing. However, it has also been
      proposed that autophagy is a cell death mechanism that could function as a backup
      when apoptosis is disabled. The fact that there are active clinical trials in
      patients both using autophagy inhibitors or inducers together with other cancer
      treatments underscores the importance of understanding and distinguishing between
      these opposing ideas. Here we discuss some of the recent work studying the role
      of autophagy with different cancer therapies.

PMID- 21178395
TI  - Rice WNK1 is regulated by abiotic stress and involved in internal circadian
      rhythm.
AB  - In Mammalian system the WNK (with no lysine kinase) serine-threonine protein
      kinase gene family is suggested to be involved in regulating ion homeostasis and
      other pathophysiological processes including cancer, hypertension and renal ion
      transport. In plant system the information about WNK genes is very poor. However,
      WNK-like genes have also been identified in plants, including ten in Arabidopsis,
      designated AtWNK1-AtWNK10. Here we report the cloning and characterization of a
      homologue of AtWNK1 gene from Oryza sativa indica cultivar Pusa Basmati-1 rice
      and designated as OsWNK1. The specific feature of this gene is lysine residue in
      kinase subdomain II, which is essential for the coordination of ATP in the active
      center and conserved among all other kinases, is absent. OsWNK1 was found to
      respond differentially under various abiotic stresses like cold, heat, salt,
      drought. OsWNK1 gene showed rhythmic expression profile under diurnal and
      circadian conditions at the transcription level. Our data indicates that OsWNK1
      in rice might play a role in abiotic stress tolerance and that it is involved in
      internal rhythm.

PMID- 21178396
TI  - Thematic issue on how autophagosomes find their targets.

PMID- 21178397
TI  - Second National Immunization Congress 2010: addressing vaccine financing for the
      future in the US.
AB  - At the 2nd National Immunization Congress held in Chicago, IL, from August 31
      September 2, 2010, partners from government, provider groups, academia, and
      manufacturers gathered to discuss the progress made and the future of financing
      child, adolescent, and adult vaccines. The meeting is a continuation of a
      solution-oriented vaccine financing dialogue held in February 2007 at the 1st
      Immunization Congress. The need for this forum arose from concerns that increased
      costs of immunization could hinder the ability of current financing and delivery
      systems to maintain access without financial barriers. Preventive care and
      additional financial coverage for vaccines are key points in federal health
      reform but some populations, especially adolescents and adults, could continue to
      experience challenges in accessing vaccines. Congress participants discussed
      adequate reimbursement in the public and private sectors for vaccine delivery and
      the potential financial resources, data, and infrastructure needed to increase
      vaccine uptake in the US. Participants agreed that partners from all sectors-
      manufacturers, providers, public health, employers, payors, insurers, and
      consumers--will collectively need to leverage their efforts to address financial
      gaps not covered by health care reform law to ensure the preventive benefits of
      vaccines are fully realized for all Americans.

PMID- 21178399
TI  - In situ photoimmunotherapy: a new hope for cutaneous melanoma patients.

PMID- 21178398
TI  - Meningococcal glycoconjugate vaccines.
AB  - Neisseria meningitidis is a major cause of invasive bacterial infections
      worldwide. For this reason, efforts to control the disease have been directed at
      optimizing meningococcal vaccines and implementing appropriate vaccination
      policies. In the past, plain polysaccharide vaccines containing purified capsular
      polysaccharides A, C, Y and W135 were developed, but failed to protect infants,
      who are at greatest risk. Experience with the conjugate Haemophilus vaccine
      suggested that this approach might well empower meningococcal vaccines. Thus, a
      very efficacious vaccine against serogroup C Neisseria meningitis was optimized
      and has been widely used in developed nations since 1999. On the basis of
      epidemiological changes in the circulation of pathogenic serogroups in the United
      States, a quadrivalent conjugate vaccine against A, C, Y and W135 serogroups
      (MenactraTM) has been developed and was approved by the U.S. FDA (Food and Drug
      Administration) in 2005. Recently, another tetravalent conjugate meningococcal
      vaccine (MenveoTM) has been licensed and made available in the United States of
      America and in the European Union. Finally, in response to large epidemics caused
      by serogroup A meningococcus in Africa, a new, safe, immunogenic and affordable
      vaccine has been developed. This review highlights the evolution of conjugate
      meningococcal vaccines in general and discusses how this kind of vaccine can
      contribute to preventing meningococcal disease.

PMID- 21178400
TI  - Tumor marker assessment: points to ponder.

PMID- 21178401
TI  - Physical activity and global genomic DNA methylation in a cancer-free population.
AB  - Changes in DNA methylation may represent an intermediate step between the
      environment and human diseases. Little is known on whether behavioral risk
      factors may modify gene expression through DNA methylation. To assess whether DNA
      methylation is associated with different levels of physical activity, we measured
      global genomic DNA methylation using bisulfite converted DNA and real time PCR
      (MethyLight) for LINE-1 in peripheral blood of 161 participants aged 45-75 years
      enrolled in the North Texas Healthy Heart Study and levels of physical activity
      using an accelerometer (Actigraph GT1M Monitor). We found that individuals with
      physical activity 26-30 min/day had a significantly higher level of global
      genomic DNA methylation compared to those with physical activity <= 10 min/day
      (beta=2.52, 95%CI: 0.70, 4.35) However, the association was attenuated and became
      statistically insignificant after multivariate adjustment (beta=1.24, 95%CI:
      0.93, 3.40). There were some suggestions of a positive association between
      physical activity and global genomic DNA methylation in non-Hispanics (beta=1.50,
      95%CI: -0.08, 3.08) that warrants further investigation.

PMID- 21178403
TI  - Traffic jams in fish bones: ER-to-Golgi protein transport during zebrafish
      development.
AB  - Extracellular matrix (ECM) proteins, cell adhesion molecules, cytokines,
      morphogens and membrane receptors are synthesized in the ER and transported
      through the Golgi complex to the cell surface and the extracellular space. The
      first leg in this journey from the ER to Golgi is facilitated by the Coat Protein
      II (COPII) vesicular carriers. Genetic defects in genes encoding various COPII
      components cause a broad spectrum of human diseases, from anemia to skeletal
      deformities. Here, we summarize our findings in zebrafish and discuss how
      mutations in COPII elements may cause specific cellular and developmental
      defects.

PMID- 21178402
TI  - Dynamics of the Rho-family small GTPases in actin regulation and motility.
AB  - The p21 Rho-family of small GTPases are master regulators of actin cytoskeleton
      rearrangements. Their functions have been well characterized in terms of their
      effects toward various actin-modulating protein targets. However, more recent
      studies have shown that the dynamics of Rho GTPase activities are highly complex
      and tightly regulated in order to achieve their specific subcellular
      localization. Furthermore, these localized effects are highly dynamic, often
      spanning the time-scale of seconds, making the interpretation of traditional
      biochemical approaches inadequate to fully decipher these rapid mechanisms in
      vivo. Here, we provide an overview of Rho family GTPase biology, and introduce
      state-of-the-art approaches to study the dynamics of these important signaling
      proteins that ultimately coordinate the actin cytoskeleton rearrangements during
      cell migration.

PMID- 21178406
TI  - Fungal x host interactions in Chromoblastomycosis: what we have learned from
      animal models and what is yet to be solved.
AB  - Animal studies with chromoblastomycosis were initiated together with the first
      descriptions of the disease. In this editorial commentary, animal models are
      briefly reviewed, and the available data based on new immunology tools are
      discussed.

PMID- 21178407
TI  - Insight into innovative approaches to battle Acinetobacter baumannii infection
      therapy struggles.

PMID- 21178408
TI  - The NK cell as a new player in the pathogenesis of HTLV-I associated neurologic
      disease.

PMID- 21178409
TI  - Pathogen-pathogen interaction: a syndemic model of complex biosocial processes in
      disease.
AB  - There is growing awareness of the health implications of fact that infectious
      agents often do not act independently; rather their disease potential is mediated
      in diverse and significant ways by their relationships with other pathogens.
      Pathogen-pathogen interaction (PPI), for example, impacts various virulence
      factors in human infection. Although still in its infancy, the study of PPI, a
      form of epidemiological synergism, is emerging as an important arena of new
      research and new understanding in health and clinical care. The aims of this
      paper are to: 1) draw attention to the role of PPI in human disease patterns; 2)
      present the syndemics model as a biosocial approach for examining the nature,
      pathways, contexts, and health implications of PPI; and 3) suggest the utility of
      this approach to PPI. Toward these ends, this paper (a) reviews three of case
      examples of alternative PPIs, (b) describes the development and key concepts and
      components of the syndemics model with specific reference to interacting
      infectious agents, (c) contextualizes this discussion with a brief review of
      broader syndemics disease processes (not necessarily involving infections
      disease), and (d) comments on the research, treatment and prevention implications
      of syndemic interaction among pathogens.

PMID- 21178410
TI  - Prolonged infection by Fonsecaea pedrosoi after antigenic co-stimulation at
      different sites in experimental murine chromoblastomycosis.
AB  - In the present study, we examined prolonged infection after antigenic co
      stimulation by inoculation of the fungus Fonsecaea pedrosoi at two different
      sites in three mouse strains (BALB/c, Swiss, and C57BL/6). Using this murine
      model of infection, we showed that antigen induction of infection at more than
      one site led to a local suppression of active lesions, which increased the time
      course of experimental chromoblastomycosis (CBM). Footpad infection with a
      simultaneous infection of the peritoneum or a mucosal site appeared to cause
      prolonged infection and frequent fungal disseminations. Using knockout (KO) mice,
      we observed that antigenic co-stimulation caused progressive illness in CD8-KO
      animals and an effective immune response in the absence of IL-10. In Xid mice, co
      stimulation provoked chronic infection (not prolonged), suggesting that B1 B
      cells play an important role in the control of fungal infection. The tissue
      response to infection was similar in all co-stimulated mouse groups, as
      anatomopathologic sections revealed multifocal lesions (granuloma-like). In
      general, these mice had acute responses at primary antigenic sites with an
      intense migration of polymorphonuclear leukocytes (PMNs), whereas the distant
      infection sites (footpad) showed signs of chronic infection. The migration of
      PMNs to the secondary site (footpad) increased in the later periods of infection,
      especially after the disappearance of the primary antigenic focus. PMN migration
      was associated with lesion-dormancy breakage and fungal elimination. Our findings
      suggest that the host inflammatory/suppression mechanisms induced by antigenic co
      stimulation to systemically fight the same pathogen act coordinately through
      responses that differ at the sites of infection between acute and chronic
      integrated healing processes that are more prolonged than an acute infection at a
      single site. However, the long persistence of fungal cells in the host may be
      linked to microbial adaptation to a parasitic infection as observed in co
      stimulated Xid mice.

PMID- 21178411
TI  - Fungal pathogen recognition by scavenger receptors in nematodes and mammals.
AB  - Macrophages are important cells in the host resistance to fungal infections, and
      fungal recognition by macrophages triggers phagocytosis, intracellular killing,
      induction of inflammatory cytokines and chemokines, and initiation of the
      adaptive immune response. All of the receptors that mediate binding and
      engulfment of fungal pathogens and the signaling pathways triggered by fungal
      pathogens that regulate anti-fungal immunity are not fully understood. Using an
      RNAi screen we recently demonstrated that the C. elegans receptors CED-1 and
      C03F11.3, and their mammalian orthologues, the scavenger receptors SCARF1 and
      CD36 mediate host defense against the fungal pathogen, Cryptococcus neoformans.
      Finally, SCARF1 and CD36 function as co-receptors by binding and engulfing fungal
      pathogens to facilitate Toll-like receptor 2 signaling. Here we will summarize
      and expand upon our previous findings.

PMID- 21178412
TI  - One step at a time: action mechanism of Sushi 1 antimicrobial peptide and derived
      molecules.
AB  - Antimicrobial peptides (AMPs) are a crucial part of the innate immune system of
      eukaryotes and present a possible alternative to common antibiotics. It is
      therefore of great importance to understand their modes of action. Using a single
      molecule approach in combination with high resolution imaging and bio-functional
      assays we were able to determine the different steps occurring during the action
      of the alpha-helical AMP Sushi 1 during bacterial lysis in spatial and temporal
      resolution in a biologically relevant context. Furthermore, we comment on the use
      of Sushi 1 as a template for new peptides to learn more about structure-function
      relationship of AMPs.

PMID- 21178413
TI  - Coupling temperature sensing and development: Hsp90 regulates morphogenetic
      signalling in Candida albicans.
AB  - Hsp90 is environmentally contingent molecular chaperone that influences the form
      and function of diverse signal transducers. Here we discuss our recent findings
      that Hsp90 regulates the morphogenetic transition from yeast to filamentous forms
      required for virulence of the most prevalent fungal pathogen of humans, Candida
      albicans, and does so via cAMP-PKA signalling. This transition is normally
      regulated by environmental cues that are contingent upon elevated temperature to
      relieve Hsp90-mediated repression of the morphogenetic program. Intriguingly,
      Hsp90 inhibition induces filamentation independent of the canonical PKA
      transcription factor Efg1, in striking similarity to a select set of
      morphogenetic stimuli. Further investigation will determine the downstream
      transcription factors through which Hsp90 regulates morphogenesis and the precise
      mechanism of Hsp90's interaction with the cAMP-PKA pathway. C. albicans is one of
      many fungal species that undergo a morphological transition in a temperature
      dependent manner, thus Hsp90's capacity to govern this key developmental program
      may provide insight into morphogenesis of diverse organisms.

PMID- 21178414
TI  - Staphylococcus aureus toxin gene hitchhikes on a transferable antibiotic
      resistance element.
AB  - Virulence and antibiotic resistance of the dangerous human pathogen
      Staphylococcus aureus are to large extent determined by the acquisition of mobile
      genetic elements (MGEs). Up to now, these elements were known to comprise either
      resistance or virulence determinants, but not a mixture of the two. Queck et al.
      now found a cytolysin gene of the phenol-soluble modulin (PSM) family within
      SCCmec elements, which contain methicillin resistance genes and are largely
      responsible for the spread of methicillin-resistant S. aureus (MRSA). The novel
      gene, called psm-mec, had a significant impact on virulence in MRSA strains that
      do not produce high levels of genome-encoded PSMs. This first example of a
      combination of toxin and resistance genes on one staphylococcal MGE shows that
      such bundling is possible and may lead to an even faster acquisition of toxin and
      resistance genes by S. aureus and other staphylococcal pathogens.

PMID- 21178415
TI  - Reinforcement of epithelial cell adhesion to basement membrane by a bacterial
      pathogen as a new infectious stratagem.
AB  - The intestinal epithelium undergoes a rapid turnover in addition to rapid
      exfoliation in response to bacterial infection, thus acting as an intrinsic
      defense against microbial intruders. It has long been questioned how mucosal
      pathogens can circumvent the intestinal defense systems. Our recent discovery of
      a bacterial ploy used by Shigella provided us with fresh insight. Shigella
      delivers OspE via the type III secretion system during multiplication within
      epithelial cells. This effector protein reinforces epithelial adherence to the
      basement membrane by interacting with integrin-linked kinase (ILK), a unique
      intracellular Ser/Thr kinase that links the cell-adhesion receptors, integrin,
      and growth factors to the actin cytoskeleton. The interaction between OspE and
      ILK increased formation of focal adhesions (FAs) and surface levels of b1
      integrin, while suppressing phosphorylation of FAK and paxillin, thus suppressing
      rapid turnover of FAs, reducing cell motility and promoting cell adhesion to
      extracellular matrix. The impact of this OspE-ILK interplay was demonstrated both
      in vitro and in vivo by infecting polarized epithelial cell monolayers and guinea
      pig colons with Shigella possessing or lacking the ospE gene. The findings thus
      establish a new class of virulence-associated factors, and provide new insight
      into the functioning of the intestinal barrier and bacterial strategies for
      circumventing it.

PMID- 21178416
TI  - The use of nitric oxide releasing nanoparticles as a treatment against
      Acinetobacter baumannii in wound infections.
AB  - Acinetobacter baumannii (Ab) is a frequent cause of hospital acquired pneumonia
      and recently has increased in incidence as the causative agent of severe disease
      in troops wounded in Afghanistan and Iraq. Ab clinical isolates are frequently
      extremely resistant to antimicrobials, significantly complicating our capacity to
      treat infections due to this pathogen. Hence, the development of innovative
      therapeutics targeting mechanisms to which the bacteria are unlikely to evolve
      resistance is urgently needed. We examined the capacity of a nitric oxide
      releasing nanoparticle (NO-np) to treat wounds infected with Ab. We found that
      the NO-nps were therapeutic in an experimental Ab murine wound model. Treatment
      with NO-nps significantly accelerated healing of infected wounds. Histological
      study demonstrated that NO-np treatment reduced suppurative inflammation,
      decreased microbial burden, and reduced the degradation of collagen. Furthermore,
      NO-np treatment alters the local cytokine milieu. In sum, we demonstrated that
      the NO-nps are an easily administered topical antimicrobial for the treatment of
      Ab wound infections, and our findings suggest that NO-nps may also be ideal for
      use in combat or disaster situations.

PMID- 21178417
TI  - Crowd control: Bacillus anthracis and quorum sensing.
AB  - In 1965, Dr. Alexander Tomasz identified a critical component of the DNA uptake
      mechanism used by competent Streptococcus pneumoniae: the pneumococci secrete a
      polypeptide that induces the expression of proteins to allow foreign DNA to pass
      through the bacterium's cell wall. This hormone-like substance was the first of
      numerous "quorum-sensing" factors that have since been identified in many
      microbial processes.  Detailed insights into the molecular mechanisms of quorum
      sensing are now emerging, owing largely to studies focusing on the ability of
      marine organisms like Vibrio fischeri and Vibrio harveyi to produce light at high
      cell densities.  The complexities of bioluminescence induction, and indeed that
      of an ever increasing group of other quorum-sensing phenotypes, show that such
      signaling pathways are not just an interesting phenomenon but rather represent a
      widespread mechanism by which bacterial populations can communicate, coordinate
      behavior and act in a cooperative manner in the environment.

PMID- 21178418
TI  - Risk based HIV retesting: back to the same old challenges.
AB  - An estimated 230,000 Americans are unaware that they have HIV infection. As a
      result, these individuals have not benefited from treatment for HIV infection and
      they may continue to spread the disease. In 2006, the Centers for Disease Control
      and Prevention (CDC) reported that 40% of adults aged 18-64 had been tested for
      HIV but only 10% had been tested within the last 12 months. A national survey
      conducted by the CDC in 2000 found that only about one-quarter of primary care
      providers and emergency physicians reported routinely testing their patients for
      HIV. To improve the performance of HIV testing, in 2006 the CDC issued
      recommendations that patients in all health care settings be offered universal,
      opt-out HIV testing. Since that time, several studies have demonstrated the
      feasibility of opt-out testing but barriers to implementation persist. Many
      states still require signed consent and counseling and other logistical
      challenges include: insufficient time, competing priorities, and inadequate
      reimbursement. Therefore, universal HIV testing remains an unrealized goal.

PMID- 21178419
TI  - Frequent HIV testing among participants of a routine HIV testing program.
AB  - Massachusetts developed a routine HIV testing program in four sites from January
      September 2002. Of the 2,502 patients tested, 453 (18.1%) reported >=2 HIV tests
      within the prior three years. In multivariate analyses, frequent HIV testing was
      associated with younger age (18-30 years, OR = 1.42), a history of injection drug
      use (OR = 6.35), and men who had sex with men (OR = 3.49). Participants who
      reported multiple sexual partners (OR = 2.17) and high risk sexual behavior (OR =
      2.02) were significantly more likely to have had a prior HIV test. Patients whose
      HIV risk was unknown had the highest association with frequent testing (OR =
      13.18). Because characteristics of frequent HIV testers may inform behavioral
      interventions, there is a need to understand the motivation for repeatedly
      accessing HIV testing services.

PMID- 21178421
TI  - Schistosoma haematobium and bladder cancer: what lies beneath?
AB  - Schistosoma haematobium is a parasitic flatworm that infects millions of people,
      mostly in the developing world, and is associated with high incidence of bladder
      cancer although why is not clear. But our group was able to define the
      mechanistic relationship for the first time between infection of S. haematobium
      and cancer. We used in vitro models to demonstrate the presence of informative
      carcinogenesis-associated phenotypes in CHO cells exposed to Sh total antigen, in
      which we showed increased cell proliferation, decreased apoptosis, up regulation
      of the anti-apoptotic molecule Bcl-2, down regulation of the tumor suppressor
      protein p27, and increased cell migration and invasion. We further discuss the
      molecular and cellular events that might be responsible for schistosomiasis
      related bladder cancer.

PMID- 21178420
TI  - Role of luxS in Bacillus anthracis growth and virulence factor expression.
AB  - Quorum-sensing (QS), the regulation of bacterial gene expression in response to
      changes in cell density, involves pathways that synthesize signaling molecules
      (auto-inducers). The luxS/AI-2-mediated QS system has been identified in both
      gram-positive and gram-negative bacteria. Bacillus anthracis, the etiological
      agent of anthrax, possesses genes involved in luxS/AI-2-mediated QS, and deletion
      of luxS in B. anthracis Sterne strain 34F2 results in inhibition of AI-2
      synthesis and a growth defect. In the present study, we created a DeltaluxS B.
      anthracis strain complemented in trans by insertion of a cassette, including luxS
      and a gene encoding erythromycin resistance, into the truncated plcR regulator
      locus. The complemented DeltaluxS strain has restored AI-2 synthesis and wild
      type growth. A B. anthracis microarray study revealed consistent differential
      gene expression between the wild-type and DeltaluxS strain, including
      downregulation of the B. anthracis S-layer protein gene EA1 and pXO1 virulence
      genes. These data indicate that B. anthracis may use luxS/AI-2-mediated QS to
      regulate growth, density-dependent gene expression and virulence factor
      expression.

PMID- 21178422
TI  - Guidance of antibiotic therapy with procalcitonin in lower respiratory tract
      infections: insights into the ProHOSP study.
AB  - In the recently published ProHOSP trial, we investigated the safety and external
      validity of procalcitonin (PCT) guidance for antibiotic therapy in patients with
      different severities of lower respiratory tract infections, mainly pneumonia. In
      this addendum, we aim to extend the initial report by reinforcing the rational of
      the PCT algorithm and by presenting more detailed data on antibiotic therapy in
      different severities of infection. In milder, mostly viral respiratory infections
      (i.e. acute or chronic bronchitis) initial prescription of antibiotics was
      markedly reduced by PCT guidance because PCT remained low in most patients. In
      pneumonia, PCT showed a severity-dependent increase and highest levels in
      patients with positive blood cultures. Thus, the main effect in pneumonia was a
      severity- and bacteremia-adapted reduction of the duration of antibiotic courses.
      In lower respiratory tract infections, PCT guidance had a differential effect on
      antibiotic exposure depending on the underlying type and severity of respiratory
      tract infection.

PMID- 21178423
TI  - Mapping the selection mechanisms by bacterial GEFs.
AB  - Mimicry of eukaryotic signaling enzymes is a common strategy used by bacterial
      pathogens to manipulate host cellular signaling. The E. coli type III effector
      protein Map belongs to a large family of bacterial virulence factors that
      activate host Rho GTPase signaling pathways through an unknown molecular
      mechanism. Our recent structural study, coupled with biochemical and functional
      assays, establishes that this family protein, including Map, IpgB1/2 and SifA/B
      secreted by E. coli, Shigella, and Salmonella respectively, acts as functional
      mimic of mammalian guanine nucleotide exchange factors (GEFs). Furthermore, we
      show that Map and its family members share a conserved mechanism with human Dbl
      GEFs for selection of various GTPase isoforms, revealing an evolutionary dynamic
      state of protein mimicry.

PMID- 21178424
TI  - Clostridium perfringens type C isolates rapidly upregulate their toxin production
      upon contact with host cells: new insights into virulence?
AB  - Since tetanus was first described by Hippocrates, the devastating diseases caused
      by pathogenic members of the gram-positive, anaerobic sporeforming genus
      Clostridium have ranked among the most dreaded afflictions of humans and domestic
      animals. The quintessential hallmark of all clostridial diseases is the
      involvement of potent protein toxins. However, except for some foodborne botulism
      cases, clostridial diseases are not intoxications involving preformed toxins;
      rather, these illnesses are true infections involving toxin production by
      bacteria growing inside the host.

PMID- 21178425
TI  - Transmissible encephalopathy agents: virulence, geography and clockwork.
AB  - Transmissible spongiform encephalopathies (TSEs) are caused by infectious agents
      with stable virulence characteristics that are not encoded by the host. Agent
      specific features of virulence include variable disease latency and tissue
      pathology in a given host, as well as the ability to spread to many species. Such
      cross-species infections contradict predictions based on the prion hypothesis.
      Recent transmissions of several human agents to normal mice and to monotypic
      neural cells in culture, underscore the existence of unique agent clades that are
      prevalent in particular geographic regions. Examples include the epidemic UK
      bovine agent (BSE) and the New Guinea kuru agent. The virus-like biology of
      unique TSE agents, including epidemic spread, mutation, and superinfection, can
      be used to systematically define features of virulence that distinguish common
      endemic from newly emerging strains.

PMID- 21178426
TI  - Significance of reduced reactivity in ELISPOT assay to RD antigens of
      Mycobacterium tuberculosis in BCG vaccinated individuals exposed to a patient
      with tuberculosis.
AB  - Children with previous BCG immunization, who were investigated for mycobacterium
      tuberculosis infection during an outbreak of tuberculosis, were found to have a
      reduced reactivity in a gamma interferon release assay for mycobacterium
      tuberculosis. This may represent reduced presence of mycobacterium tuberculosis
      in BCG vaccinated individuals, who eliminated infection due to enhancement of the
      immune response by immunization. Alternatively bacterial load may have been
      suppressed below detection threshold of the body's immune system. Future research
      needs to develop methods of direct and specific detection of low bacterial loads
      of mycobacterium tuberculosis in vivo. One method worth further development is
      radio-immuno-szintigraphy, which has been successful in detection of
      mycobacterium tuberculosis in vivo in animal studies.

PMID- 21178427
TI  - Relevance of serology and molecular methods for detection of Hepatitis B virus in
      Egyptian children with hematological malignancy.

PMID- 21178428
TI  - From the outside in and the inside out: Antifungal immune responses in
      Caenorhabditis elegans.

PMID- 21178430
TI  - Granulomatous-like immune reaction and hepatic fibrosis induced by Schistosoma
      haematobium immature worms.
AB  - Golden hamsters were inoculated with Schistosoma haematobium cercariae to examine
      histological lesions at different time points over an 18 month period of
      infection. Hamsters were sacrificed 26 weeks and 82 weeks after inoculation. The
      parasite was found in the blood and in the liver of infected animals as was
      expected, but we found exclusively male worms, no female worms nor eggs.
      Interestingly we observed unexpected hepatic lesions induced by S. haematobium
      adult male worms alone in the golden hamster, characteristic of schistosome eggs.
      Samples from liver, kidneys, lungs, bladder and gastrointestinal tract were
      collected during necropsy to evaluate injuries induced by S. haematobium. Notably
      we observed hepatitis in the liver of infected hamsters, no lesions were found in
      other organs. We also found liver fibrosis in infected hamsters. This study
      provides further experimental evidence for the role that schistosome worms, and
      their derived antigens, may play in the pathology of the infection and modulation
      of liver chronic inflammation in the murine model of schistosomiasis.

PMID- 21178429
TI  - The fatty acid synthase fasn-1 acts upstream of WNK and Ste20/GCK-VI kinases to
      modulate antimicrobial peptide expression in C. elegans epidermis.
AB  - An important part of the innate immune response of the nematode C. elegans to
      fungal infection is the rapid induction of antimicrobial peptide gene expression.
      One of these genes, nlp-29, is expressed at a low level in adults under normal
      conditions. Its expression is up-regulated in the epidermis by infection with
      Drechmeria coniospora, but also by physical injury and by osmotic stress. For
      infection and wounding, the induction is dependent on a p38 MAP kinase cascade,
      but for osmotic stress, this pathway is not required. To characterize further the
      pathways that control the expression of nlp-29, we carried out a genetic screen
      for negative regulatory genes. We isolated a number of Peni (peptide expression
      no infection) mutants and cloned one. It corresponds to fasn-1, the nematode
      ortholog of vertebrate fatty acid synthase. We show here that a pathway involving
      fatty acid synthesis and the evolutionary conserved wnk-1 and gck-3/Ste20/GCK-VI
      kinases modulates nlp-29 expression in the C. elegans epidermis, independently of
      p38 MAPK signaling. The control of the antimicrobial peptide gene nlp-29 thus
      links different physiological processes, including fatty acid metabolism,
      osmoregulation, maintenance of epidermal integrity and the innate immune response
      to infection.

PMID- 21178431
TI  - Asymptomatic bacteriuria among HIV positive pregnant women.
AB  - The prognostic significance of asymptomatic bacteriuria resides in the
      observation that the prevalence is, relatively, high in persons with certain
      medical conditions, such as diabetes mellitus and pregnancy. This prevalence
      might, even, be higher in patients with human immunodeficiency virus infection.
      Hence, this study set out to determine the prevalence of asymptomatic bacteriuria
      among symptom free and newly enrolled HIV infected pregnant women attending PMTCT
      unit of Antiretroviral Clinic of University College Hospital, Ibadan, Nigeria
      between 1st May and 30th September 2007.Information was obtained on the socio
      demographic characteristics of the subjects, CD4 count and viral load. Microbial
      culture was carried out on aseptically collected urines from the patients.
      Statistical analysis was done with SPSS 12 package. There were 161 analyzable
      samples from the participants. The mean age and gestational age at presentation
      of participants was 30.49 +/- 4.3 years and 27.3 +/- 3.2 weeks, respectively with
      modal parity of 2. Twenty-five (15.5%) of the urine samples significantly grew
      bacteria. The CD4 cells were significantly lower and the viral loads
      significantly higher(250.52 vs. 355.57 cells/mm3; 88,731 vs. 55,384 copies/ml; p
      = <0.0000) for the urine culture positive patients. Eshcherichia coli were
      isolated in 48%, Proteus in 16.0%, Klebsiella in 8.0% and Staphylococcus aureus
      in 28.0% of the urine positive cultures.The study showed that the prevalence of
      asymptomatic bacteriuria among PLWHAs is high. The microbial isolate from the
      urine samples were not different from those of HIV-negative patients.

PMID- 21178432
TI  - Comparison of ante-mortem assays to assess progression/regression of
      paratuberculosis in individual dairy animals.
AB  - Johne's disease, caused by Mycobacterium avium, subspecies paratuberculosis (MAP)
      is becoming increasingly widespread on dairy farms worldwide, due in part, to the
      absence of vaccine/drug or curative modalities.  This spread is of concern since
      MAP is at the center of a controversy as to its role in Crohn's disease.  None of
      the methods presently available to define paratuberculosis in cattle have been
      examined for their ability to assess progression/regression of any treatment or
      intervention of this disease   The research presented herein, therefore was
      designed to assess the reliability and accuracy of available ante-mortem assays
      to predict disease change of individual animals undergoing a probiotic,
      potentially therapeutic, treatment.  Paratuberculosis positive (n = 75) and
      negative (n = 10) animals were longitudinally monitored over their natural
      lifetimes with specific serum antibody and fecal shedding assays, and for
      development of end-stage clinical disease.  Longitudinal, increasing/decreasing
      serum ELISA values were associated with, and predictive of,
      progression/regression of disease.  Changes in fecal shedding and serum AGID were
      of value at only specific stages.  Documentation that ELISA-positive animals were
      positive for paratuberculosis was done by a compilation of ELISA-independent
      assays--succumbing with end-stage clinical disease, autopsy, AGID, and MAP fecal
      shedding.

PMID- 21178433
TI  - Assessment of Dietzia subsp. C79793-74 for treatment of cattle with evidence of
      paratuberculosis.
AB  - The objective of the present investigation was to determine whether the bacterium
      Dietzia subsp. C79793-74, previously shown to inhibit growth of Mycobacterium
      subsp. paratuberculosis under in vitro culture conditions, has therapeutic value
      as a probiotic for adult cattle with paratuberculosis.  Animals were obtained
      from several herds with evidence of disease based on seropositivity and/or fecal
      shedding.  Sixty-eight cows with initial evidence of Stage II or III
      paratuberculosis and 2 with an initial Stage IV disease were evaluated
      longitudinally.  Animals were either treated daily with variable, disease
      dependent doses of Dietzia (n = 48) or left untreated (n = 22).  Clinical aspects
      of disease (diarrhea, emaciated, cachectic and appetite) were recorded until the
      animal recovered or required euthanasia due to advanced clinical paratuberculosis
      or other severe conditions.  Paratuberculosis parameters-antibody serology
      (ELISA, AGID) and fecal culture-were longitudinally monitored over the lifetime
      of each animal.  The results indicated that daily treatment with Dietzia was
      therapeutic for paratuberculosis cows based on: (a) longitudinal decline in ELISA
      values only occurred in animals that were treated; (b) prolonged survival was
      dependant upon treatment--the length being directly associated with low initial
      ELISA values; and (c) treated animals were the only ones cured of disease. 
      Further investigations are envisaged to determine optimal, long-term dosages that
      may result in even better therapeutic outcomes as well as to evaluate potential
      application for therapy of the Johne's disease, human-counterpart, Crohn's
      disease.

PMID- 21178434
TI  - Evaluation of mycobacterial virulence using rabbit skin liquefaction model.
AB  - Liquefaction is an important pathological process that can subsequently lead to
      cavitation where large numbers of bacilli can be coughed up which in turn causes
      spread of tuberculosis in humans. Current animal models to study the liquefaction
      process and to evaluate virulence of mycobacteria are tedious. In this study, we
      evaluated a rabbit skin model as a rapid model for liquefaction and virulence
      assessment using M. bovis BCG, M. tuberculosis avirulent strain H37Ra, M.
      smegmatis, and the H37Ra strains complemented with selected genes from virulent
      M. tuberculosis strain H37Rv. We found that with prime and/or boosting
      immunization, all of these live bacteria at enough high number could induce
      liquefaction, and the boosting induced stronger liquefaction and more severe
      lesions in shorter time compared with the prime injection. The skin lesions
      caused by high dose live BCG (5*10 (6) ) were the most severe followed by live M.
      tuberculosis H37Ra with M. smegmatis being the least pathogenic. It is of
      interest to note that none of the above heat-killed mycobacteria induced
      liquefaction. When H37Ra was complemented with certain wild type genes of H37Rv,
      some of the complemented H37Ra strains produced more severe skin lesions than
      H37Ra. These results suggest that the rabbit skin liquefaction model can be a
      more visual, convenient, rapid and useful model to evaluate virulence of
      different mycobacteria and to study the mechanisms of liquefaction.

PMID- 21178435
TI  - Characterization of a 5-azacytidine-induced developmental Aspergillus fumigatus
      variant.
AB  - The hypomethylating agent 5-azacytidine (5AC) is widely used in patients at risk
      of invasive mycoses. We sought to determine whether 5AC affects the developmental
      competence and virulence of Aspergillus fumigatus. Incubation of A. fumigatus
      strain 293 with 5AC induced high-frequency conversion to a fluffy-variant (Af293
      (FL) ). The conidiation defect was bypassed by exposing Af293 (FL) to light
      during the initial 18 hours of growth on solid media. Transcriptional profiling
      revealed differential expression of multiple genes involved in G-protein
      signaling, including a putative G-protein coupled photoreceptor (opsin),
      suggesting that impaired signaling through a light-responsive pathway upstream of
      brlA is responsible for this phenotype. Af293 (FL) was fully virulent in fruit
      fly and murine models of invasive aspergillosis. Moreover, Af293 (FL)
      overexpressed aspergillopepsin F, had increased elastase activity and was more
      angioinvasive than the parental wild-type strain. The 5AC-induced A. fumigatus
      fluffy variant illustrates the potential effects of chemotherapeutic agents on
      the developmental and pathobiologic characteristics of opportunistic fungi.

PMID- 21178436
TI  - Bioluminescent fungi for real-time monitoring of fungal infections.
AB  - Novel luciferase reporters have been developed that allow real-time monitoring of
      infections by the fungal pathogens Candida albicans and Aspergillus fumigatus.
      Although these reporters still suffer limitations in the context of invasive
      infections, they provide unprecedented tools to monitor superficial infections
      and the efficacy of antifungal drugs or vaccines. In particular, the sensitivity
      and ease of detection of the cell-surface Gaussia princeps luciferase developed
      for C. albicans should make it a powerful tool for functional genomics studies in
      this and other pathogenic fungi.

PMID- 21178437
TI  - Chronic immune activation in the T cell compartment of HCV/HIV-1 co-infected
      patients.
AB  - Activation of innate and adaptive immune mechanisms in response to infection is
      necessary to control and clear infections. However, chronic immune activation in
      human immunodeficiency virus 1 (HIV-1) infection has a series of detrimental
      effects and is a major driving force in HIV-1 disease progression. We recently
      found that patients with chronic hepatitis C virus (HCV)/HIV-1 co-infection
      display sharply elevated immune activation as determined by expression of CD38 in
      T cells. High immune activation was observed despite that these patients were on
      effective antiretroviral therapy (ART), which usually brings down activation
      levels in HIV-infected people. HCV treatment with pegylated interferon-alpha
      (IFNalpha) and ribavirin reduced activation, and this was at first glance
      unexpected as IFNalpha is believed to be involved in driving activation. Here, we
      briefly summarize these findings and discuss them in context of the emerging
      roles of the gut barrier and the liver in chronic immune activation and viral
      disease progression.

PMID- 21178438
TI  - Host-microbe interactions in stem cell transplantation: recognizing Candida in
      infection and inflammation.
AB  - Host-pathogen interactions at epithelial barriers play an important role in
      health and disease. This also applies to the clinical setting of stem cell
      transplantation (SCT) in which deregulated sensing of microbes and their cell
      wall components by pattern recognition receptors (PRRs) can contribute to
      inflammatory and infectious complications. The role of Candida species herein has
      recently been rediscovered since a 'loss-of-function' Y238X polymorphism in
      dectin-1, a C-type lectin receptor recognizing the beta-1,3-glucan motif of
      Candida, resulted in diminished membrane expression and lower cytokine responses
      upon beta-1,3-glucan recognition, and was associated with increased Candida
      colonization of SCT recipients, rendering them at risk for candidaemia. In
      addition, Candida colonization was associated with an increased incidence of
      acute graft-versus-host disease (GvHD), but only in those individuals with the
      wild-type dectin-1 allele. The Th17 mediated immune responses might provide a
      common link in these processes, as they have recently been implicated in anti
      Candida immunity as well as the pathogenesis of GvHD. These new insights suggest
      that immunogenetics could contribute to a more individualized risk-based strategy
      for managing SCT recipients, for example concerning antifungal prophylaxis. In
      addition, modulating host-pathogen interactions by selectively modulating PRR
      activity could be exploited in SCT to achieve better outcomes.

PMID- 21178439
TI  - Fungal hydrophobins form a sheath preventing immune recognition of airborne
      conidia.
AB  - Aspergillus fumigatus is the most ubiquitous and the most threatful airborne
      fungal pathogen. In the atmosphere, there is thousands of conidia/m (3)
      originating from more than hundred fungal genera, which enter the host through
      the respiratory system and are eliminated by the innate immune defences. But how
      do A. fumigatus conidia survive long enough in the lung withstanding the host
      killing reactions? We demonstrated recently the role of the spore-surface rodlet
      layer made up of hydrophobic protein (hydrophobin) in preventing their
      recognition by the immune system. Upon removal of this rodlet layer by chemical,
      genetic or biological means, the resulting morphotypes were immunostimulatory in
      effect, confirming the essentiality of the role of the rodlet layer for the
      fungal survival in vivo.

PMID- 21178440
TI  - An endocytic CARriage tale: Adenoviruses internalization and trafficking in
      neurons.
AB  - In immune-competent hosts, adenoviruses (Ads) are mild pathogens that cause
      mainly infections of the respiratory and ocular tracks. The advent of Ad-based
      gene transfer vectors made the understanding of their interaction with the host
      cellular machinery an intensive field of research over the last decade. As
      studies focused primarily on epithelial-like cells, the mechanism of neuronal
      uptake of Ads was still missing. Using a combination of biochemical and cell
      biology approaches, we characterized the axonal trafficking pathway used by the
      canine adenovirus serotype 2 (CAV-2) to reach the neuronal soma. We showed that
      CAV-2 and CAR (coxsackievirus and adenovirus receptor) are entering a vesicular
      pathway coupled to the axonal transport machinery. The lumen of the multivalent
      Rab7 (+) vesicles that transport CAV-2 and CAR is, surprisingly, pH neutral.
      Among other issues, our study opens numerous questions concerning the neuronal
      function of CAR.

PMID- 21178441
TI  - Manipulation of host angioneogenesis: A critical link for understanding the
      pathogenesis of invasive mold infections?
AB  - Despite progress over the last decade, opportunistic mold infections continue to
      be associated with high rates of morbidity and mortality in immunocompromised
      patients. Given the propensity of molds to invade blood vessels, vasculopathy may
      be a barrier to effective delivery of antifungal drugs to infected tissue. In a
      recent study (Ben-Ami R et al. Blood, 2009), we found that A. fumigatus
      suppresses endothelial cell migration, differentiation and capillary tube
      formation both in vitro and in an animal model system. This effect is mediated by
      secreted secondary metabolites such as gliotoxin. Herein, I discuss the potential
      implications of how invasive molds modulate host angiogenesis in experimental and
      clinical mold infections. Strategies that employ reversal of vasculopathy,
      neutralization of metabolites that inhibit endothelial function, exploration of
      pro-angiogenic factors as diagnostic or prognostic markers affected patients will
      likely be the focus of future studies. This complex, yet emerging field might add
      another level of knowledge and therapeutic choices in the management of these
      devastated infections.

PMID- 21178442
TI  - Mitochondria and the regulation of hypervirulence in the fatal fungal outbreak on
      Vancouver Island.
AB  - In our recent paper, we demonstrated that the hypervirulence exhibited by a
      lineage of the fatal fungal pathogen Cryptococcus gattii is associated with its
      mitochondrial gene expression and an unusual mitochondrial morphology. As an
      important organelle, the mitochondrion has been linked to various cellular
      activities, but its role in modulating virulence of pathogens remains unclear. In
      this addendum, the potential role of mitochondria in determining virulence in
      eukaryotic pathogens is discussed along with future experiments that may lead to
      an improved understanding of this topic.

PMID- 21178443
TI  - Linking cellular actin status with cAMP signaling in Candida albicans.
AB  - The fungal pathogen Candida albicans has a remarkable ability to switch growth
      forms. Particularly, the yeast-to-hyphae switch is closely linked with its
      virulence. A range of chemicals and conditions can promote hyphal growth
      including serum, peptidoglycan, CO2, neutral pH, and elevated temperature. All
      these signals act essentially through the adenylyl cyclase Cyr1 that synthesizes
      cAMP. Cells lacking Cyr1 are completely defective in hyphal growth. Recently,
      cellular actin status is found to influence cAMP synthesis. However, how Cyr1
      senses and processes multiple external and internal signals to produce a
      contextually proper level of cAMP remains unclear. We hypothesized that Cyr1
      itself possesses multiple sensors for different signals and achieves signal
      integration through a combined allosteric effect on the catalytic center. To test
      this hypothesis, we affinity-purified a Cyr1-containing complex and found that it
      could enhance cAMP synthesis upon treatment with serum, peptidoglycan or CO2 in
      vitro. The data indicate that the complex is an essentially intact
      sensor/effector apparatus for cAMP synthesis. The complex contains two more
      subunits, the cyclase-associated protein Cap1 and G-actin. We discovered that G
      actin plays a regulatory role, rendering cAMP synthesis responsive to actin
      dynamics. These findings shed new lights on the mechanisms that regulate cAMP
      mediated responses in fungi.

PMID- 21178444
TI  - Coevolution between pathogen-derived proteinases and proteinase inhibitors of
      host insects.
AB  - Virulence is thought to coevolve as a result of reciprocal selection between
      pathogens and their hosts. This paper focuses on coevolution between microbial
      proteinases operating as virulence factors and host defense molecules of insects.
      Owing to shorter generation times and smaller genomes, microbes exhibit a high
      evolutionary adaptability in comparison with their hosts. Indeed, the latter can
      only compete with pathogens if they evolve mechanisms providing a comparable
      genetic plasticity. Gene or domain duplication and shuffling by recombination is
      the driving force behind the countermeasures in host defense effectors. Recent
      literature provides evidence for both diversifications of fungal proteinases
      involved in pathogenesis and expansion host proteinase inhibitors subsets
      contributing to insect innate immunity. For example, the pathogen-associated
      spectrum of proteolytic enzymes encompasses thermolysin-like metalloproteinases
      that putatively promoted the evolution of corresponding host inhibitors of these
      virulence factors which complement the insect repertoire of antimicrobial defense
      molecules. Beyond mutual diversification of effector molecules coevolution
      resulted also in sophisticated molecular adaptations of host insects such as
      sensing and feedback-loop regulation of microbial metalloproteinases and
      corresponding countermeasures of pathogens providing evasion of host immunity
      induced by these virulence factors.

PMID- 21178445
TI  - Ozonation of human HIV-infected plasmas for producing a global vaccine: How HIV
      patients may help fight the HIV pandemia.
AB  - A vaccine against HIV able to generate properly neutralizing antibodies and an
      efficacious cytotoxic T lymphocyte response is of paramount importance. We are
      proposing a novel approach based on the collection of thousand small HIV-infected
      human plasma samples for preparing a global vaccine, able to counteract HIV
      diversity and mutagenicity. The pooled plasmas will undergo several steps for
      sterilizing and inactivating HIV, possibly other contaminant viruses and other
      pathogens. The critical step is the prolonged and controlled exposure of plasmas
      to ozone so that finally each ml of plasma has interacted with a precise dose of
      ozone. To inactivated plasma, both therapeutic human albumin and ozonated ethyl
      oleate are added for enhancing a proficient absorption and reaction with the
      immune system of the vaccine. The need of a partner collaboration for developing
      the production and the preliminary testing of the vaccine is essential.

PMID- 21178446
TI  - Insights into the biofilm lifestyle of enterococci.

PMID- 21178447
TI  - Checks and balances: the ocular response to infection.
AB  - Bacterial corneal infections threaten vision. With the widespread use of contact
      lenses and the increasing number of vision-correction (refractive) surgeries, the
      number of bacterial corneal infection (keratitis) cases has dramatically
      increased over the past decade. These infections are often blinding, as bacteria
      multiply in the corneal epithelium and stroma, provoking inflammatory cell
      migration into the cornea, and ultimately damage or destruction of corneal
      tissue.

PMID- 21178449
TI  - Local changes in rates of group A Streptococcus disease and antibiotic resistance
      are associated with geographically widespread strain turnover events.
AB  - This study addresses the effects of dynamic strain turnover and antibiotic
      prophylaxis on rates of group A Streptococcus (GAS) antibiotic resistance and
      disease. The authors analyzed the strain distributions, disease rates, and
      patterns of antibiotic resistance of 802 GAS isolates collected from 2002 through
      2007. These samples were collected from patients with GAS infection symptoms at
      10 military facilities. Macrolide resistance peaked at 25% during 2004, due to
      the geographically widespread dominance of a single resistant strain (M75). The
      resistant strain was not retained regardless of local patterns of macrolide use,
      and resistance rates decreased upon replacement of M75 with macrolide-susceptible
      strains. Disease rates were similarly correlated with dominance of specific M
      types. Statistical analysis revealed temporal correlations between strain
      distributions at multiple locations. Only the most common strains yielded enough
      data at multiple sites for statistically significant comparison of temporal
      fluctuations in dominance, but these (including M44, M3, M18, M118, and M6) all
      yielded highly significant temporal correlations of 90% or greater on yearly
      scales. As expected given the complexity and variability of strain distributions
      on shorter time scales, analysis on a monthly scale yielded lower degrees of
      positive correlation (31-62%), but in this case all significant correlations were
      still positive. Shifts in antibiotic resistance profiles and disease rates at
      specific sites appear to be associated with strain replacements happening on
      larger scales, independent of antibiotic use at individual sites.

PMID- 21178450
TI  - Examination of maternal gingival crevicular fluid for the presence of selected
      periodontopathogens implicated in the pre-term delivery of low birthweight
      infants.
AB  - BACKGROUND: Reports show that more than 20 million infants world-wide are born
      prematurely with 95% of all pre-term births occurring in developing countries.
      Oral colonization of gram-negative anaerobes has been implicated as a risk factor
      for preterm delivery of low birth weight infants. MATERIALS AND METHODS: This
      study comprised 200 women admitted to the department of obstetrics and gynecology
      of the teaching hospital of Butare in Rwanda. Gingival crevicular fluid was
      collected from each quadrant of the mother's mouth (using paper points) within 24
      hours of delivery. A dichotomous score of presence or absence of gingival
      inflammation was recorded for each patient along with demographic data such as
      age, marital status etc. Samples were examined by PCR for the presence of
      Aggregatibacter actinomycetemcomitans and selected members of the red and orange
      complexes described by Socransky et al., (1998), and their presence associated
      with age, gingival inflammation and pregnancy outcomes. RESULTS: Association of
      bacterial species with the risk of periodontal disease and thus the risk of
      preterm delivery was only observed when they occurred in pairs or groups of three
      or more. Aa appeared to be a necessary co-factor for significant associations of
      bacterial groups with the variables recorded.

PMID- 21178448
TI  - Response of corneal epithelial cells to Staphylococcus aureus.
AB  - Staphylococcus aureus is a leading cause of invasive infection. It also infects
      wet mucosal tissues including the cornea and conjunctiva. Conflicting evidence
      exists on the expression of Toll-like receptors by human corneal epithelial
      cells. It was therefore of interest to determine how epithelial cells from this
      immune privileged tissue respond to S. aureus. Further, it was of interest to
      determine whether cytolytic toxins, with the potential to cause ion flux or
      potentially permit effector molecule movement across the target cell membrane,
      alter the response. Microarrays were used to globally assess the response of
      human corneal epithelial cells to S. aureus. A large increase in abundance of
      transcripts encoding the antimicrobial dendritic cell chemokine, CCL20, was
      observed. CCL20 release into the medium was detected, and this response was found
      to be largely TLR2 and NOD2 independent. Corneal epithelial cells also respond to
      S. aureus by increasing the intracellular abundance of mRNA for inflammatory
      mediators, transcription factors, and genes related to MAP kinase pathways, in
      ways similar to other cell types. The corneal epithelial cell response was
      surprisingly unaffected by toxin exposure. Toxin exposure did, however, induce a
      stress response. Although model toxigenic and non-toxigenic strains of S. aureus
      were employed in the present study, the results obtained were strikingly similar
      to those reported for stimulation of vaginal epithelial cells by clinical toxic
      shock toxin expressing isolates, demonstrating that the initial epithelial
      cellular responses to S. aureus are largely independent of strain as well as
      epithelial cell tissue source.

PMID- 21178452
TI  - Interferon interplay helps tissue cells to cope with SARS-coronavirus infection.
AB  - SARS coronavirus (SARS-CoV), the causative agent of severe acute respiratory
      syndrome, is a versatile pathogen armed with a host of factors countering the
      antiviral type I interferon (IFN) system. Hence, tissue cells infected with SARS
      CoV are unable to launch an IFN response. Plasmacytoid dendritic cells, however,
      produce high levels of IFN after infection. We recently demonstrated that minute
      amounts of IFN applied before infection (IFN priming) can ameliorate the IFN
      response of tissue cells to SARS-CoV. IFN priming of SARS-CoV-infected cells
      activated genes for IFN transcription, IFN signaling, antiviral effector
      proteins, ubiquitinylation and ISGylation, antigen presentation, and other
      cytokines and chemokines, whereas IFN treatment or infection alone had no major
      effect. Thus, the IFN which is produced by plasmacytoid dendritic cells could
      enable tissue cells to at least partially overturn the SARS-CoV-induced block in
      innate immune activation.

PMID- 21178451
TI  - Regulation of type III secretion system 1 gene expression in Vibrio
      parahaemolyticus is dependent on interactions between ExsA, ExsC, and ExsD.
AB  - Vibrio parahaemolyticus ExsA is the transcriptional regulator for type III
      secretion system 1 (T3SS1) while ExsD blocks T3SS1 expression. Herein we show
      that deletion of exsC from V. parahaemolyticus blocked synthesis of T3SS1
      dependent proteins under inducing conditions (contact with HeLa cells), while in
      trans complementation of the DeltaexsC strain with wild-type exsC restored
      protein synthesis. Under non-inducing conditions (Luria broth plus salt), in
      trans expression of exsC in a wild-type strain resulted in synthesis and
      secretion of T3SS1-dependent proteins. Deletion of exsC does not affect the
      synthesis of ExsA while expression of T3SS1 genes is independent of ExsC in the
      absence of ExsD. Co-expression of recombinant proteins with different antigenic
      tags demonstrated that ExsC binds ExsD and that the N-terminal amino acids of
      ExsC (positions 7 to 12) are required for binding. Co-expression and purification
      of antigentically tagged ExsA and ExsD demonstrated that ExsD directly binds ExsA
      and presumably prevents ExsA from binding promoter regions of T3SS1 genes.
      Collectively these data demonstrate that ExsD binds ExsA to block expression of
      T3SS1 genes, while ExsC binds ExsD to permit expression of T3SS1 genes. ExsA,
      ExsC, and ExsD from V. parahaemolyticus appear to be functional orthologues of
      their Pseudomonas aeruginosa counterparts.

PMID- 21178453
TI  - Fungal pathogen recognition by the NLRP3 inflammasome.
AB  - The relationship between host and opportunistic pathogen is a tenuous one and an
      injudicious response to pathogen-associated molecular patterns may result in a
      hostile environment to potentially beneficial commensal organisms. Therefore,
      discrimination between pathogenic forms, causing cellular damage, and innocuous
      commensal forms of microbes is critical in maintaining homeostasis. The NLRP3
      inflammasome has recently been identified as playing an important role in
      recognition of the fungal pathogen Candida albicans. Here we will review these
      findings and discuss the role of the NLRP3 inflammasome in initiating an innate
      immune response to invasive C. albicans.

PMID- 21178454
TI  - Abnormal CEACAM6 expression in Crohn disease patients favors gut colonization and
      inflammation by adherent-invasive E. coli.
AB  - Abnormal expression of CEACAM6 is observed at the apical surface of the ileal
      epithelium in Crohn's disease (CD) patients, and CD ileal lesions are colonized
      by pathogenic adherent-invasive Escherichia coli (AIEC). The paper of Carvalho et
      al. recently reported that CD associated AIEC colonize and induce strong gut
      inflammation in transgenic mice expressing human CEACAM6 acting as a receptor for
      type 1 pili produced by AIEC bacteria. AIEC also induce CEACAM6 expression by
      intestinal epithelial cells directly by adhering to host cells and indirectly via
      increased secretion of TNF-alpha from AIEC-infected macrophages. Patients
      expressing a basal level of CEACAM6 in ileum could be predisposed to develop
      ileal CD and blocking interaction between type 1 pili and CEACAM6 might serve as
      a specific means of disrupting the colonization and the subsequent inflammatory
      amplification loop.

PMID- 21178455
TI  - Human origin for avian pathogenic Staphylococcus aureus.
AB  - Staphylococcus aureus is a major human pathogen associated with nosocomial and
      community-acquired infections, and is also responsible for several economically
      important infections of livestock. However, the evolutionary origin of animal
      strains and the potential for cross-species transmission has not been well
      examined. We recently traced the origin of a common S. aureus clone which is a
      significant cause of morbidity in the global broiler poultry industry. We
      provided evidence that it evolved from a single human to poultry host jump which
      was followed by extensive genetic diversification including acquisition of novel
      mobile genetic elements and loss of virulence gene function. The clone has since
      been disseminated widely to several different continents presumably through
      globalization of the poultry industry. In the current article, we summarise the
      findings of the paper, discuss their implications and speculate on the potential
      for other S. aureus cross-species transfer events.

PMID- 21178456
TI  - C-type lectins in immune defense against pathogens: the murine DC-SIGN homologue
      SIGNR3 confers early protection against Mycobacterium tuberculosis infection.
AB  - Host defense against pathogens involves various receptors expressed in cells of
      the immune system. Upon pathogen recognition, these proteins mediate a plethora
      of effector functions, such as the secretion of key protective cytokines and
      other immune mediators. These receptors include C-type lectins (CTLs), which are
      increasingly being recognized as major players in the host response to microbes.
      One particular CTL, DCSIGN/CD209, recognizes conserved sugar motifs in a number
      of viruses, parasites and bacteria. In particular, we and others have shown that
      DC-SIGN plays an important part in the recognition by dendritic cells and
      macrophages of Mycobacterium tuberculosis, the causal agent of tuberculosis in
      humans. Using the mouse as a model: host for M. tuberculosis, we recently showed
      that the DC-SIGN homologue SIGNR3 mediates protection against the tubercle
      bacillus, possibly through secretion of the key cytokines interleukin 6 and tumor
      necrosis factor. Here, we summarize and discuss these findings and their
      implications for the design of future studies aiming to improve our understanding
      of the role of DC-SIGN and other C-type lectins in immunity to mycobacteria and
      other pathogens.

PMID- 21178457
TI  - Subcellular localization of the alphaherpesvirus serine/threonine kinase Us3 as a
      determinant of Us3 function.
AB  - The Us3 serine threonine kinases perform multiple roles in alphaherpesvirus
      infection and can localize to distinct subcellular compartments. Transient
      expression of Us3 in cells results in two dramatic alterations of the actin
      cytoskeleton: production of actin-based filamentous processes (FPs); and
      breakdown of actin stress fibres giving rise to rounded cell morphology. In our
      recent study on FPs induced by HSV-2 Us3, we noted that FP formation was
      diminished when HSV-2 Us3 was trapped within the nucleus following treatment of
      transfected cells with leptomycin B (LMB). This observation suggested that
      subcellular localization of Us3 could be a determinant of Us3-induced FP
      formation. Here, we review what is known regarding the effect of subcellular
      localization of Us3 on FP production and on actin stress fibre breakdown and
      discuss the potential significance of studies aimed at defining the requirements
      for subcellular localization of Us3.

PMID- 21178459
TI  - The human microbiome harbors a diverse reservoir of antibiotic resistance genes.
AB  - The increasing levels of multi-drug resistance in human pathogenic bacteria are
      compromising our ability to treat infectious disease. Since antibiotic resistance
      determinants are readily exchanged between bacteria through lateral gene
      transfer, there is an increasing interest in investigating reservoirs of
      antibiotic resistance accessible to pathogens. Due to the high likelihood of
      contact and genetic exchange with pathogens during disease progression, the human
      microflora warrants special attention as perhaps the most accessible reservoir of
      resistance genes. Indeed, numerous previous studies have demonstrated substantial
      antibiotic resistance in cultured isolates from the human microflora. By applying
      metagenomic functional selections, we recently demonstrated that the functional
      repertoire of resistance genes in the human microbiome is much more diverse than
      suggested using previous culture-dependent methods. We showed that many
      resistance genes from cultured proteobacteria from human fecal samples are
      identical to resistance genes harbored by human pathogens, providing strong
      support for recent genetic exchange of this resistance machinery. In contrast,
      most of the resistance genes we identified with culture independent metagenomic
      sampling from the same samples were novel when compared to all known genes in
      public databases. While this clearly demonstrates that the antibiotic resistance
      reservoir of the large fraction of the human microbiome recalcitrant to culturing
      is severely under sampled, it may also suggest that barriers exist to lateral
      gene transfer between these bacteria and readily cultured human pathogens. If we
      hope to turn the tide against multidrug resistant infections, we must urgently
      commit to quantitatively characterizing the resistance reservoirs encoded by our
      diverse human microbiomes, with a particular focus on routes of exchange of these
      reservoirs with other microbial communities.

PMID- 21178458
TI  - Aging, imbalanced inflammation and viral infection.
AB  - Older people experience enhanced susceptibility to viral infections and
      subsequent superimposed bacterial infections. Based on both experimental and
      clinical studies, this susceptibility is thought to be due to declining immune
      responses. However, our work indicates that older people may succumb to viral
      infection due to exaggerated immune responses as aged mice produce higher serum
      levels of the inflammatory mediator IL-17 than younger mice upon herpes viral
      infection. These age-elevated IL-17 responses induce a lethal immune pathology
      during viral infection. Early during the course of infection natural killer T
      cells (NKT-cells) are major contributors to the elevated IL-17 response in aged
      mice. These responses synergize with defective viral clearance with aging noted
      by impaired IFN-alpha responses by plasmacytoid DCs. Our results indicate that
      novel anti-inflammatory drugs may resolve imbalanced inflammation and improve
      outcomes in older people infected with viruses.

PMID- 21178460
TI  - Functional characteristics of the malaria parasite's "chloroquine resistance
      transporter": implications for chemotherapy.
AB  - Chloroquine (CQ) was the best and most heavily used drug in the fight against
      malaria. However, the effectiveness of CQ has declined with the emergence and
      spread of CQ-resistant (CQR) Plasmodium falciparum parasites. The primary
      determinant of CQ resistance in P. falciparum is mutations in the parasite's
      'chloroquine resistance transporter' (PfCRT). These mutations result in a marked
      reduction in the accumulation of CQ by the parasite; however the mechanism by
      which this is achieved was not understood. We have recently shown that the
      mutations confer upon PfCRT the ability to transport CQ away from its site of
      accumulation and action. Sensitive and resistance-conferring forms of the protein
      (PfCRT (CQS) and PfCRT (CQR) , respectively) were expressed at the surface of
      Xenopus laevis oocytes, and it was found that PfCRT (CQR) (but not PfCRT (CQS))
      transports CQ. Here we discuss and expand upon our findings to address the
      question of whether PfCRT (CQR) behaves as a carrier or a channel, and how this
      distinction has significant implications for the treatment of CQR P. falciparum
      with CQ or CQ-like drugs. In particular we relate this to the example of Guinea
      Bissau, where high doses of CQ are routinely used to treat CQR P. falciparum
      malaria.

PMID- 21178461
TI  - Deciphering the role of phage in the cystic fibrosis airway.
AB  - Cystic fibrosis (CF) is a fatal genetic disorder hallmarked by chronic and
      persistent microbial infections of the lungs and airways. Much attention has been
      paid to describing microbial communities and microbial pathogenesis in CF,
      however, viral communities have been largely ignored. We recently published a
      metagenomic study characterizing viral communities in the sputum of CF and Non-CF
      individuals for the first time. There was a striking difference in metabolic
      functions encoded by phage in CF versus Non-CF individuals. Regardless of which
      viral taxa were present, CF-associated phage shared a common core metabolism that
      reflected the disease state and aberrant airway physiology. Here, this finding is
      discussed further and its implications for the role of phage and the nature of
      phage-microbe interactions in the CF airway are explored.

PMID- 21178462
TI  - Proteases and phosphatases during Leishmania-macrophage interaction: paving the
      road for pathogenesis.
AB  - The outcome of Leishmania infection depends both on host and pathogen factors.
      Macrophages, the specialized host cells for uptake and intracellular development
      of Leishmania, play a central role in the control of infection. Leishmania has
      evolved strategies to downregulate host cell functions, largely mediated by the
      parasite-induced activation of macrophage protein tyrosine phosphatases (PTPs).
      We have recently identified PTP1B and TCPTP as two additional PTPs engaged upon
      Leishmania infection and have unraveled an intimate interaction between the
      Leishmania surface protease GP63 and host PTPs, which mediates a mechanism of
      cleavage-dependent PTP activation. Here we discuss new perspectives for GP63
      mediated parasite virulence and propose putative mechanisms of GP63
      internalization into host macrophages and access to intracellular substrates.

PMID- 21178464
TI  - Altering the balance between pathogen containing vacuoles and lysosomes: a lesson
      from Salmonella.
AB  - Intracellular pathogens like Salmonella, Mycobacteria and Listeria has several
      survival mechanisms to combat the host assault. One of the very interesting
      strategies observed in case of these intracellular bacteria is their ability to
      survive and replicate in specialized vacuole inside the infected cells.
      Salmonella, in its turn, resides in a low pH and nutritionally depleted
      compartment termed as Salmonella containing vacuole (SCV) which never fuses with
      the lysosomes. Using macrophage cells we have recently demonstrated a unique
      characteristic of the SCV. Our data indicates that during Salmonella cell
      division, the SCV also divides and always a single SCV contains only one
      bacterium. This actually increases the total SCV number in the Salmonella
      infected cells. Further, Salmonella infection reduces the lysosome numbers and
      gives the pathogen an upper hand in the infected cells. Here we will summarize
      and expand upon our previous findings.

PMID- 21178463
TI  - SNARE motif: a common motif used by pathogens to manipulate membrane fusion.
AB  - To penetrate host cells through their membranes, pathogens use a variety of
      molecular components in which the presence of heptad repeat motifs seems to be a
      prevailing element. Heptad repeats are characterized by a pattern of seven,
      generally hydrophobic, residues. In order to initiate membrane fusion, viruses
      use glycoproteins-containing heptad repeats. These proteins are structurally and
      functionally similar to the SNARE proteins known to be involved in eukaryotic
      membrane fusion. SNAREs also display a heptad repeat motif called the "SNARE
      motif". As bacterial genomes are being sequenced, microorganisms also appear to
      be carrying membrane proteins resembling eukaryotic SNAREs. This category of
      SNARE-like proteins might share similar functions and could be used by
      microorganisms to either promote or block membrane fusion. Such a recurrence
      across pathogenic organisms suggests that this architectural motif was
      evolutionarily selected because it most effectively ensures the survival of
      pathogens within the eukaryotic environment.

PMID- 21178465
TI  - The relevance of heat shock regulation in fungal pathogens of humans.
AB  - Despite being obligately associated with warm-blooded animals, Candida albicans
      expresses a bona fide heat shock response that is regulated by the evolutionarily
      conserved, essential heat shock transcription factor Hsf1. Hsf1 is thought to
      play a fundamental role in thermal homeostasis, adjusting the levels of essential
      chaperones to changes in growth temperature, for example in febrile patients.
      Hsf1 also regulates the expression of Hsp90, which controls the yeast-hypha
      transition in C. albicans, and we argue, might also control morphogenesis in
      other fungal pathogens of humans.

PMID- 21178466
TI  - Revisiting the Escherichia coli polysaccharide capsule as a virulence factor
      during urinary tract infection: contribution to intracellular biofilm
      development.
AB  - The treatment of urinary tract infections (UTIs) is becoming increasingly
      challenging as uropathogenic Escherichia coli (UPEC) becomes more resistant to
      the most widely prescribed oral antibiotics. The treatment of UTIs may also be
      complicated by the inherent lifestyle of UPEC in the urinary tract, revealed in
      recent studies demonstrating bacterial invasion into bladder epithelial cells,
      the formation of intracellular bacterial communities (IBCs; biofilm-like colonies
      in the host cell cytosol), and chronic intracellular persistence with subversion
      of normal immune surveillance. Identifying key targets in the pathogenesis of
      UTIs, including IBC formation, will be crucial to replenish the arsenal of
      treatments for UTIs. Focused on elucidating bacterial components that underpin
      the development of IBCs, Anderson et al. recently demonstrated a novel role for
      the K capsule polysaccharide in IBC formation. Without K capsule, intracellular
      UPEC failed to undergo normal IBC formation, the intracellular bacteria failed to
      preclude neutrophil infiltration, and UPEC did not undergo serial cycles of
      intracellular proliferation, resulting in attenuation of the infection. This
      study also demonstrated an interconnection between sialic acid homeostasis and
      IBC formation, demonstrating a unique role for this amino sugar in biofilm
      formation. This study provides evidence for an expanded role for K capsule in the
      intracellular and extracellular pathogenesis of UTI, and provides additional
      rationale for the development of small molecule inhibitors of capsule biogenesis
      as anti-virulence therapeutics.

PMID- 21178467
TI  - Epidemionics: from the host-host interactions to the systematic analysis of the
      emergent macroscopic dynamics of epidemic networks.
AB  - One of the most critical issues in epidemiology revolves around the bridging of
      the diverse space and time scales stretching from the microscopic scale, where
      detailed knowledge on the immune mechanisms, host-microbe and host-host
      interactions is often available, to the macroscopic population-scale where the
      epidemic emerges, the questions arise and the answers are required. In this paper
      we show how the so called Equation-Free approach, a novel computational framework
      for multi-scale analysis, can be exploited to efficiently analyze the macroscopic
      emergent behavior of complex epidemic models on certain type of networks by
      acting directly on the multi-scale simulation. The methodology can be used to
      bypass the need of derivation of closures for the emergent population-level
      equations providing a systematic computational strict approach for macroscopic
      level analysis. We illustrate the methodology through a stochastic individual
      based model with agents acting on two different networks: a random regular and an
      Erdos-Renyi network. We construct the macroscopic bifurcation diagrams and locate
      the critical points that mark the onset of emergent hysteresis behavior which are
      associated with disease outbreaks. Finally, we perform a rare-events analysis
      that may in principle be used to estimate the mean time of possible outbreaks of
      phenomenologically latent infectious diseases.

PMID- 21178468
TI  - Evidence-based practice: Management of combined toxoplasma meningo-encephalitis
      and Pneumocystis pneumonia in HIV.
AB  - Although both Pneumocystis jiroveci pneumonia (PCP) and Toxoplasma gondii
      encephalitis are common opportunistic infections (OI) in USA & UK, combined
      infection has been only very rarely reported. After National Library of Medicine
      and Medline searches, only one case report by Tsai et al. has been found. Two
      additional cases will be presented and the management challenges associated with
      treating these two infections simultaneously discussed.

PMID- 21178469
TI  - Candida infection and colonization in critically ill surgical patients.

PMID- 21178470
TI  - Q&A: Institute for OneWorld Health--Fulfilling the promise of medicine for the
      developing world. Interview by Kyle Funk.

PMID- 21178471
TI  - Candida infection and colonization among non-trauma emergency surgery patients.
AB  - BACKGROUND: Candida is a significant pathogen among critically ill patients.
      However, candidiasis among non-trauma emergency surgery (NTES) patients has not
      been previously investigated. Herein we describe the incidence of both
      colonization and infection from Candida and risk factors for invasive disease in
      this population. METHODS: For this retrospective single center study we included
      all NTES patients with ICU stay >=4 days from May 1(st), 2002 to April 30(th),
      2007. Patients were divided into 3 non-overlapping groups: 1) patients with
      Candida-infection, 2) patients with Candida colonization and 3) patients with
      negative Candida cultures. Groups were compared by univariate and multivariate
      analyses to identify significant risk factors for invasive candidiasis. RESULTS:
      Of all 289 eligible patients, 63 (21.7%) fulfilled the criteria for Candida
      infection and 110 (38%) were included in the Candida colonization group.
      Interestingly, from the 63 patients with invasive candidiasis, 25 (39.7%) were
      infected by a non-albicans species. Upon multivariate analyses, ventilator
      associated pneumonia (VAP) (Odds Ratio [OR]: 2.34; 95%, Confidence Interval [CI]:
      1.213-4.533, p = 0.0112), bacteremia (OR: 4.778; 95%CI: 1.519-15.029, p = 0.0075)
      and surgical complications (OR: 3.903; 95%CI: 1.335-11.412, p = 0.0129) were
      independent risk factors for the development of Candida infection. Candida
      infection and colonization were both found to correlate with approximately
      $40,000-100,000 mean additional costs). Interestingly, candidemia was associated
      with 63% all-cause mortality. For all other forms of candidiasis, mortality was
      not significantly different among groups. CONCLUSION: We found that Candida
      infection is alarmingly high among NTES patients with prolonged intensive care
      unit (ICU) stay. Surgical complications and bacterial infections (VAP and
      bacteraemia) were significantly correlated with the development of candidiasis.
      Candidiasis reached a rate of 21.7/100 discharges, which is significantly higher
      than most established high-risk populations for candidiasis. Future studies
      should review the need for antifungal prophylaxis on this population.

PMID- 21178472
TI  - Candida infection and colonization among trauma patients.
AB  - BACKGROUND: Data on Candida infection among critically ill trauma patients are
      limited and not recently updated. Here we study the epidemiology and economic
      impact of Candida and examine potential risk factors for Candida infection in
      this population. METHODS: In this 5-year retrospective study, all severely
      injured patients with >=4 days of intensive care unit stay were included, with
      the primary outcome being Candida infection. We identified 3 distinct patient
      groups: 1) The Candida infection, 2) The Candida colonization and 3) the Candida
      free group. All comparisons between groups with p-values <=0.2 from the
      univariate analysis were entered into stepwise logistic regression to identify
      independent risk factors for candidiasis. RESULTS: 374 patients were included.
      Upon comparisons between groups, candidiasis patients received significantly more
      blood transfusions (p=0.013), antibiotics (p=0.005), and total parenteral
      nutrition (TPN) (p=0.004), had a longer duration of mechanical ventilation (MV)
      (p=0.008) and underwent more laparotomy procedures than Candida free patients
      (56.5% versus 16.4%; p<0.001). Surgical complications (13% versus 1.4%; p=0.013),
      injury of the upper (13% versus 0.9%; p=0.007) and lower gastrointestinal tract
      (8.7% versus 0.9%; p=0.048), and bacterial wound or intra-abdominal infections
      (17.4% versus 1.9%; p=0.004) were also more common in candidiasis patients. Upon
      multivariate analysis, patients receiving TPN had 7-fold higher odds for
      developing candidiasis (Odds ratio [OR]: 7.2; 95% Confidence interval [CI]: 2.6
      19.4; p=0.0001). Other predisposing factors included laparotomy (OR: 3.8, 95% CI:
      1.5-9.9; p=0.0057) and female gender (OR: 5.7; 95% CI: 2.1-15.6; p=0.0007).
      Average total hospital charges were higher for patients with Candida infection
      compared to patients with Candida colonization or without a positive Candida
      culture. CONCLUSIONS: TPN, laparotomy, and female gender independently predict
      the development of candidiasis among trauma patients. Severely injured women
      requiring laparotomy and TPN therapy should be carefully managed for the
      possibility of increased risk for candidiasis.

PMID- 21178473
TI  - Brucella alters endocytic pathway in J774 macrophages.
AB  - Brucella is a facultative intracellular bacterium which causes chronic infections
      in mammals by surviving and replicating within host cells. The putative role of
      the endoplasmic reticulum (ER) in the formation of the phagosome in non
      professional phagocytes is supported by several research groups, but still leaves
      open the question of the fate of Brucella inside professional phagocytes and its
      resistance mechanisms therein. Macrophages are particularly important for the
      survival and spreading of Brucella during infection. The intracellular transport
      of Brucella in these cells has not been thoroughly characterized. To study the
      maturation process of Brucella-containing phagosomes in phagocytes, we
      comparatively monitored the intracellular transport of a virulent strain (2308)
      with two vaccine strains (S19 and RB51) in J 774 macrophages. Then, we compared
      the behavior of all three strains studied through transmission electron
      microscopy. The results indicate that the virulent strain not only occupies two
      different kinds of compartments but also alters the endocytic pathway of the cell
      it parasitizes, unlike what has been reported for non-professional phagocytes,
      like HeLa cell. Besides, differences are observed in the behavior of both
      Brucella abortus vaccine strains.

PMID- 21178474
TI  - Detection of an infectious retrovirus, XMRV, in blood cells of patients with
      chronic fatigue syndrome.
AB  - In October 2009, we reported the first direct isolation of infectious xenotropic
      murine leukemia virus-related virus (XMRV). In that study, we used a combination
      of biological amplification and molecular enhancement techniques to detect XMRV
      in more than 75% of 101 patients with chronic fatigue syndrome (CFS). Since our
      report, controversy arose after the publication of several studies that failed to
      detect XMRV infection in their CFS patient populations. In this addenda, we
      further detail the multiple detection methods we used in order to observe XMRV
      infection in our CFS cohort. Our results indicate that PCR from DNA of
      unstimulated peripheral blood mononuclear cells is the least sensitive method for
      detection of XMRV in subjects' blood. We advocate the use of more than one type
      of assay in order to determine the frequency of XMRV infection in patient cohorts
      in future studies of the relevance of XMRV to human disease.

PMID- 21178475
TI  - A novel C-di-GMP effector linking intracellular virulence regulon to quorum
      sensing and hypoxia sensing.
AB  - Pathogenic bacteria have evolved sophisticated mechanisms to respond and adapt to
      diverse environmental conditions, especially at the early stage of host-pathogen
      interaction. Their ability to sense the changes at the infection court and to
      coordinate virulence gene expression among members, are critical for overwhelming
      host defense responses and establishing infection. In a recently published paper,
      we have demonstrated that the Clp of X. campestris pv. campestris (Xcc), is a
      novel c-di-GMP binding protein. In this addendum, I intend to provide detailed
      discussion on the role and the mechanism of Clp as a molecular link in connecting
      Xcc intracellular virulence regulon to quorum sensing and hypoxia sensing, which
      are two of the important environmental cues that influence the bacterial
      pathogenicity. In addition, I compare the c-di-GMP effector Clp with its close
      homologue Crp, which is a well-characterized cAMP receptor, in the context of
      ligand specificity, mode of action, and their corresponding biological functions.
      The identification of Clp as a c-di-GMP receptor has provided further
      understanding how a bacterial pathogen could accommodate and integrate various
      signal inputs for its benefit. Significantly, this study has also presented solid
      evidence that Crp-family proteins can be categorized into two functional groups,
      i.e., cAMP receptor and c-di-GMP effector, based on the corresponding signature
      amino acid residues in the conserved cNMP binding domain.

PMID- 21178476
TI  - Integrins as triggers of Epstein-Barr virus fusion and epithelial cell infection.
AB  - Epstein-Barr virus is a ubiquitous orally-transmitted human herpesvirus that is
      carried by most of the adult population. It establishes latent infections in B
      lymphocytes, reactivates periodically from latency and can be amplified in
      epithelial cells where it is thought more commonly to undergo lytic replication.
      Entry into either cell involves fusion of the virus envelope with a cell
      membrane. Fusion with a B cell requires four envelope glycoproteins, gB and a
      ternary complex of gHgLgp42. Fusion is triggered by an interaction between gp42
      and HLA class II. Fusion with an epithelial cell requires three envelope
      glycoproteins, gB and a binary complex of gHgL. The presence of gp42 blocks
      infection and blocks the interaction of gHgL with a specific receptor on the
      epithelial cell surface. We recently demonstrated that both integrins alphavbeta6
      and alphavbeta8 can serve as specific receptors for gHgL and that on binding to
      gHgL, even in a soluble form, can provide the trigger for direct virus fusion
      with the epithelial cell plasma membrane. It reveals yet another way in which an
      integrin can be used by a pathogen to invade a cell.

PMID- 21178477
TI  - Basophils induce Th2 immunity: is this final answer?
AB  - Despite that basophils represent less than 0.5% of circulating leukocytes, recent
      studies have begun to unveil their potent immunoregulatory functions, i.e.,
      induction of Th2 immunity. It is believed that basophils are capable of doing so
      primarily by secreting key Th2-inducing cytokines, namely IL-4 and Thymic Stromal
      Lymphopoietin (TSLP), and by functioning as professional antigen presenting
      cells. However, we have recently demonstrated that Th2 immunity can develop in
      the absence of basophils or IL-4 during helminth infection. In this review, how
      basophils may (and may not) contribute to the development of Th2 immunity in vivo
      is discussed.

PMID- 21178478
TI  - Janus-headed communication promotes bacterial cooperation and cheating: is quorum
      sensing useful against infections?
AB  - In a detailed spatially explicit simulation study (Czaran & Hoekstra, 2009) we
      have shown that quorum sensing (QS)--the ability of bacteria to detect the local
      density of their clonemates in their immediate neighbourhood--might have evolved
      in synergism with cooperative behavior, i.e., the production of "public goods"
      like virulence factors for the common benefit of the cooperators, in spite of the
      fact that both cooperation and QS communication can be cheated (exploited) by
      mutant strains. In particular, we found that 1) cooperation requires an effective
      kin selection mechanism to operate, which is automatically supplied by the
      limited mobility of bacteria; 2) QS communication extends the scope for
      cooperation considerably, and cooperation maintains the selective advantage of QS
      communication, even if 3) different types of cheaters are always present and
      coexistent with "honest" phenotypes in a quasi-equilibrium. These predictions are
      validated by experimental results and field data by now, and medical applications
      of the results have been suggested.

PMID- 21178479
TI  - Intermolecular interactions between HD-GYP and GGDEF domain proteins mediate
      virulence-related signal transduction in Xanthomonas campestris.
AB  - In the plant pathogen Xanthomonas campestris pv. campestris (Xcc) a two component
      system comprising RpfG and the complex sensor kinase RpfC is implicated in
      sensing and responding to the cell-cell signaling molecule DSF to positively
      regulate the synthesis of virulence factors such as extracellular enzymes,
      biofilm structure and motility. RpfG is a two-component regulator with a CheY
      like receiver domain attached to an HD-GYP cyclic di-GMP phosphodiesterase
      domain. In a recent paper we showed that that the physical interaction of RpfG
      with two proteins with a diguanylate cyclase (GGDEF) domain, acts to control a
      sub-set of RpfG-regulated virulence functions. These protein-protein interactions
      required the conserved GYP motif in the HD-GYP domain of RpfG and were dependent
      on DSF signaling. Here we discuss these findings, considering in particular
      different scenarios for the role of RpfG in multiple signaling pathways involving
      cyclic di-GMP that impinge on virulence.

PMID- 21178480
TI  - Enhancement of bacterial virulence by antibody neutralization of immune
      activating toxins.
AB  - Bacterial pathogens release a number of toxins that are able to form pores in
      target host cells, which can result in their destruction. Due to this property of
      this subgroup of toxins, they are considered virulence factors. A lesser known
      ability of these toxins when present at lower concentrations that are
      insufficient for host cell lysis to occur, is their activation of host immune
      cells. The Panton-Valentine Leukocidin (PVL) secreted by an alarming percentage
      of Staphylococcus aureus causing community-acquired infections, is one such:
      toxin. Due to the low inoculum of S. aureus we used to establish skin abscesses
      in a murine model of infection, lower amounts of PVL are likely to be present
      early in infection, hence, the proinflammatory properties of PVL may be more
      evident. Our data not only suggested that this was indeed the case, but we also
      showed that antibodies directed to PVL neutralized immune activation by this
      toxin resulting in a less robust host innate immune response. Thus, given the
      high levels of antibodies to PVL present in healthy individuals, these antibodies
      may directly enhance the virulence of PVL-producing S. aureus by dampening the
      innate immune response to infection. Since many pore-forming toxins share this
      dual property of concentration-dependent host cell lysis and immune activation,
      it is interesting to speculate that antibodies raised to some bacterial toxins
      may have the opposite intended outcome of directly enhancing bacterial virulence
      instead of controlling infection.

PMID- 21178481
TI  - Aspartate chemosensory receptor signalling in Campylobacter jejuni.
AB  - The human bacterial pathogen Campylobacter jejuni is able to respond to
      environmental stimuli utilising chemotactic motility. The bacterial senses
      external molecules via transmembrane sensory proteins called Transducer Like
      Proteins, TLPs. The specificity of the Tlp1 chemoreceptor (Cj1506c) of C. jejuni
      as the aspartate receptor, CcaA, and its role in chemotaxis signalling pathway
      were characterised by genetic and biochemical approaches including amino acid and
      small molecule arrays, Saturation Transfer Difference NMR spectroscopy, and
      mutational analysis. Yeast two-hybrid and three-hybrid analysis of protein
      protein interactions showed that CcaA chemotactic signal was preferentially
      passed through CheV, rather than the CheW homologue of the chemotaxis signalling
      pathway allowing a new model for the C. jejuni chemotactic signalling pathway to
      be postulated.

PMID- 21178482
TI  - Antagonistic crosstalk between type I and II interferons and increased host
      susceptibility to bacterial infections.
AB  - Type I and II interferons (IFNs alphabeta and gamma) have opposing effects on
      immune resistance to certain pathogenic bacteria. While IFNgamma generally plays
      a protective role, IFNalphabeta exacerbates Listeria monocytogenes and
      Mycobacterium tuberculosis infections. Our findings provided evidence that this
      increased susceptibility reflects a novel antagonistic cross talk between
      IFNalphabeta and IFNgamma. Macrophages infected with L. monocytogenes strains
      that induce IFNalphabeta production responded poorly to IFNgamma, as measured by
      reduced phosphorylation of STAT1 and reduced IFNgamma-dependent gene expression.
      The impaired responsiveness to IFNgamma correlated with reduced expression of its
      receptor, IFNGR, by both infected and bystander macrophages. Down regulation of
      IFNGR was dependent on responsiveness to IFNgamma and mimicked by recombinant
      IFNbeta. Mice lacking responsiveness to IFNalphabeta (IFNAR1 (-/-)) retained high
      IFNGR expression, developed higher expression of MHC-II on macrophages and DCs,
      and were more resistant to systemic L. monocytogenes infection--but only in the
      presence of IFNgamma. Thus, the ability of IFNalphabeta to down regulate IFNGR
      provides an explanation for its ability to reduce responsiveness to IFNgamma and
      to increase host susceptibility to bacterial infection. It remains to be
      determined whether and how such antagonistic interferon crosstalk benefits the
      host.

PMID- 21178483
TI  - IL-17 in protective immunity to intracellular pathogens.
AB  - The identification of a new T cell subset referred to as T helper 17 (Th17) cells
      and its role in protective immunity against extracellular bacterial infections is
      well established. In contrast, initial studies suggested that the IL-23-IL-17
      pathway was not required for protection against intracellular pathogens such as
      mycobacterial infections. However, recent studies demonstrate that Th17-IL-23
      pathway may play a crucial role in protective immunity against other
      intracellular pathogens by regulating the innate and adaptive immune responses.
      The current outlook on the role of IL-23-IL-17 pathway in protective immunity to
      intracellular pathogens is discussed here.

PMID- 21178484
TI  - TAL effector-DNA specificity.
AB  - TAL effectors are important virulence factors of bacterial plant pathogenic
      Xanthomonas, which infect a wide variety of plants including valuable crops like
      pepper, rice, and citrus. TAL proteins are translocated via the bacterial type
      III secretion system into host cells and induce transcription of plant genes by
      binding to target gene promoters. Members of the TAL effector family differ
      mainly in their central domain of tandemly arranged repeats of typically 34 amino
      acids each with hypervariable di-amino acids at positions 12 and 13. We recently
      showed that target DNA-recognition specificity of TAL effectors is encoded in a
      modular and clearly predictable mode. The repeats of TAL effectors feature a
      surprising one repeat-to-one-bp correlation with different repeat types
      exhibiting a different DNA base pair specificity. Accordingly, we predicted DNA
      specificities of TAL effectors and generated artificial TAL proteins with novel
      DNA recognition specificities. We describe here novel artificial TALs and discuss
      implications for the DNA recognition specificity. The unique TAL-DNA binding
      domain allows design of proteins with potentially any given DNA recognition
      specificity enabling many uses for biotechnology.

PMID- 21178486
TI  - Antimicrobial peptides: the ancient arm of the human immune system.
AB  - The production of peptides and small proteins with microbicidal activity
      collectively called antimicrobial peptides (AMPs) is commonly considered to be a
      primitive mechanism of immunity and has been extensively studied in insects and
      other non-vertebrate organisms. In addition, a variety of AMPs present in
      amphibian skin secretion has been well characterised. There is now increasing
      evidence that AMPs play a crucial role in human immunity as well. Virtually all
      human tissues and cells typically exposed to microbes are able to produce AMPs.
      Important AMPs belonging to two structurally distinct classes, known as the
      defensins and the cathelicidins, are mainly produced by epithelial cells and
      neutrophils. AMPs significantly contributing to the chemical skin barrier are
      represented by dermcidin, psoriasin and RNase 7. The antimicrobial activity of
      saliva largely depends on histidine-rich AMPs known as histatins. Many more, in
      part less well-known AMPs and AMP-like proteins exist that exhibit various
      additional functions, apart from their antimicrobial properties. Among them, the
      neutrophil granule proteins azurocidin and cathepsin G are members of a family of
      serine-protease homologues called serprocidins and play a role in the regulation
      of the immune response and degradation of extracellular matrix proteins
      respectively. As another AMP-like protein of the neutrophil granule content,
      bactericidal/permeability increasing protein (BPI) is both able to permeabilise
      bacterial membranes and to function as an opsonin. The whey acidic protein (WAP)
      domain containing class of AMPs, including secretory leukocyte protease inhibitor
      (SLPI), elafin and trappin-2, is equally important in inhibition of neutrophil
      serine proteases and killing of microbes. Certain CC or CXC chemokines are known
      to possess antimicrobial properties and therefore are called kinocidins. Several
      kinocidins, including thrombocidin-1 and -2, are contained in the alpha-granules
      of platelets. A cytoplasmic AMP described as ubiquicidin turned out to be
      identical with the strongly basic ribosomal protein S30. Proteolytic cleavage of
      the histone protein H2A in the stomach gives rise to an AMP initially described
      as buforin I. Adrenomedullin is a hormone-like AMP exhibiting vasodilatory and
      hypotensive effects. Lysozyme is mainly known for its cell wall degrading
      activity, but is also capable of non-enzymatic killing of bacteria. An iron
      binding protein present in milk and other secretions named lactoferrin was shown
      to possess antimicrobial and antiviral activity and has been implicated in
      protection against cancer. Clinical studies on the treatment of infectious
      diseases have been performed with artificial peptides derived from human
      lactoferrin, histatins and BPI in addition to porcine protegrins, frog magains
      and bovine indolicidin. Omiganan, representing an indolicidin derivative, has
      been demonstrated to be effective in the treatment of acne and catheter-related
      local infections and is currently considered to be the most promising AMP-based
      drug candidate.

PMID- 21178485
TI  - The role of the influenza virus RNA polymerase in host shut-off.
AB  - Viruses induce an antiviral host response by activating the expression of
      antiviral host genes. However, viruses have evolved a wide range of strategies to
      counteract antiviral host responses. One of the strategies used by many viruses
      is the general inhibition of host gene expression, also referred to as a host
      shut-off mechanism. Here we discuss our recent findings that influenza virus
      infection results in the inhibition and degradation of host RNA polymerase II
      (Pol II) and that the viral RNA polymerase plays a critical role in this process.
      In particular, we found that Pol II is ubiquitylated in influenza virus infected
      cells and ubiquitylation can be induced by the expression of the RNA polymerase.
      Moreover, the expression of an antiviral host gene could be inhibited by the over
      expression of the RNA polymerase. Both ubiquitylation and the inhibition of the
      host gene were dependent on the ability of the RNA polymerase to bind to Pol II.
      Further studies will be required to understand the interplay between the host and
      viral transcriptional machineries and to elucidate the exact molecular mechanisms
      that lead to the inhibition and degradation of Pol II as a result of viral RNA
      polymerase binding. These findings extend our understanding of how influenza
      virus counteracts antiviral host responses and underpin studies into the
      mechanisms by which the RNA polymerase determines virulence.

PMID- 21178487
TI  - Successful, combined long-term treatment of cerebral aspergillosis in a liver
      transplant patient.
AB  - Invasive aspergillosis has long been recognized as one of the most significant
      and often fatal opportunistic fungal infections in liver transplant recipients.
      We report a case of a liver transplant recipient who developed an Aspergillus
      fumigatus brain abscess that produced significant neurologic symptoms. The
      patient was managed successfully with a combination of surgery and medical
      treatment with Voriconazole. To our knowledge, this is the second such case
      reported in the literature.

PMID- 21178488
TI  - Strongyloides hyperinfection syndrome presenting as enterococcal meningitis in a
      low-endemicity area.

PMID- 21178489
TI  - ERG oncogene modulates prostaglandin signaling in prostate cancer cells.
AB  - Androgen dependent induction of the ETS related gene (ERG) expression in more
      than half of all prostate cancers results from gene fusions involving regulatory
      sequence of androgen regulated genes (i.e. TMPRSS2, SLC45A3 and NDRG1) and
      protein coding sequence of the ERG. Emerging studies in experimental models
      underscore the functions of ERG in prostate tumorigenesis. However, biological
      and biochemical functions of ERG in prostate cancer (CaP) remain to be
      elucidated. This study suggests that ERG activation plays a role in prostaglandin
      signaling because knockdown of ERG expression in TMPRSS2-ERG fusion containing
      CaP cells leads to altered levels of the 15-hydroxy-prostaglandin dehydrogenase
      (HPGD), a tumor suppressor and prostaglandin catabolizing enzyme, and
      prostaglandin E2 (PGE2) . We demonstrate that HPGD expression is regulated by the
      binding of the ERG protein to the core promoter of this gene. Moreover,
      prostaglandin E2 dependent cell growth and urokinase-type plasminogen activator
      (uPA) expression are also affected by ERG knockdown. Together, these data imply
      that the ERG oncoprotein in CaP cells positively influence prostaglandin mediated
      signaling, which may contribute to tumor progression.

PMID- 21178490
TI  - Ebolavirus VP35 is a multifunctional virulence factor.
AB  - Ebola virus (EBOV) is a member of the filoviridae family that causes severe
      hemorrhagic fever during sporadic outbreaks, and no approved treatments are
      currently available. The multifunctional EBOV VP35 protein facilitates immune
      evasion by antagonizing antiviral signaling pathways and is important for viral
      RNA synthesis. In order to elucidate regulatory mechanisms and to develop
      countermeasures, we recently solved the structures of the Zaire and Reston EBOV
      VP35 interferon inhibitory domain (IID) in the free form and of the Zaire EBOV
      VP35 IID bound to dsRNA. Together with biochemical, cell biological, and
      virological studies, our structural work revealed that distinct regions within
      EBOV VP35 IID contribute to virulence through host immune evasion and viral RNA
      synthesis. Here we summarize our recent structural and functional studies and
      discuss the potential of multifunctional Ebola VP35 as a therapeutic target.

PMID- 21178491
TI  - Methods for using Galleria mellonella as a model host to study fungal
      pathogenesis.
AB  - The facile inoculum delivery and handling of the insect Galleria mellonella make
      it a desirable model for the study of fungal pathogenesis. Here we present
      methods to study fungal virulence, filamentation and fungal cell associates with
      insect hemocytes using Candida albicans and Cryptococcus neoformans to illustrate
      the use of this model. The two types of fungi cause distinct infections thus we
      compare and contrast the infection characteristics observed in G. mellonella. The
      protocols presented herein can be adapted to the study of other fungal pathogens
      using G. mellonella as an infection model.

PMID- 21178492
TI  - An easy and economical in vitro method for the formation of Candida albicans
      biofilms under continuous conditions of flow.
AB  - Candida albicans can develop biofilms on medical devices and these biofilms are
      most often nourished by a continuous flow of body fluids and subjected to shear
      stress forces. While many C. albicans biofilm studies have been carried out using
      in vitro static models, more limited information is available for biofilms
      developed under conditions of flow. We have previously described a simple flow
      biofilm model (SFB) for the development of C. albicans biofilms under conditions
      of continuous media flow. Here, we recount in detail from a methodological
      perspective, this model that can be assembled easily using materials commonly
      available in most microbiological laboratories. The entire procedure takes
      approximately two days to complete. Biofilms developed using this system are
      robust, and particularly suitable for studies requiring large amounts of biofilm
      cells for downstream analyses. This methodology simplifies biofilm formation
      under continuous replenishment of nutrients. Moreover, this technique mimics in
      vivo flow conditions, thereby making it physiologically more relevant than the
      currently dominant static models.

PMID- 21178493
TI  - The peculiar ways of Brucella survival: looking through the keyhole.

PMID- 21178494
TI  - The growing promise of Toll-deficient Drosophila melanogaster as a model for
      studying Aspergillus pathogenesis and treatment.
AB  - Despite considerable progress over recent years, the prognosis of invasive
      aspergillosis (IA) remains unfavorable, reflecting an incomplete understanding of
      Aspergillus pathogenesis and suboptimal antifungal efficacy in vivo. Mammalian
      host systems including rodents and rabbits are important tools in elucidating
      antifungal drug activity and the immunopathogenesis of IA. Nonetheless, they are
      hampered by limitations that impose a "bottleneck" in mass screening of novel
      antifungal compounds and putative Aspergillus virulence factors including their
      cost, labor intensity and ethical constraints. Drosophila melanogaster is an
      invertebrate host with a long tract record of genetic studies and a simple, yet
      highly conserved innate immune system. Herein, we describe our experience using
      this fly model as a facile, non-laborious, inexpensive pathosystem for high
      throughput screening of novel antifungal compounds and putative Aspergillus
      mutants, and studying antifungal innate immunity. We present three infection
      protocols (i.e., injection, rolling, ingestion) that introduce Aspergillus either
      directly into the hemolymph or at different epithelial surfaces of Toll-deficient
      Drosophila flies. As a proof of principle, we demonstrate attenuated virulence of
      known hypovirulent Aspergillus strains and protection of Aspergillus-infected
      flies given oral Aspergillus-active agents such is voriconazole. These protocols
      can be adapted for similar studies of other fungal pathogens. Crossing and
      generation of Toll-deficient Drosophila flies takes 3 weeks; Aspergillus conidial
      preparation takes 3 days; fly inoculation depending on the infection assay takes
      1 to 6-8 hours; and assessment of fly survival, Aspergillus strain virulence,
      Drosophila innate host parameters and/or drug activity takes 4-8 days.

PMID- 21178495
TI  - SUMOylation and bacterial pathogens.
AB  - During infection, bacterial pathogens interfere with many different post
      translational modifications of the host cell to promote their own survival and
      replication. By stimulating or counteracting host post-translational
      modifications, these pathogens may control locally and specifically the fate and
      function of host factors critical for the infection process. Besides
      phosphorylation or ubiquitylation, for which many examples of modulation by
      pathogens exist, a post-translational modification called SUMOylation was
      recently shown to be targeted by pathogenic bacteria.

PMID- 21178497
TI  - New tricks new ways: exploitation of a multifunctional enzyme arginase by
      pathogens.

PMID- 21178496
TI  - Glucuronoxylomannan, galactoxylomannan, and mannoprotein occupy spatially
      separate and discrete regions in the capsule of Cryptococcus neoformans.
AB  - The capsular polysaccharides of Cryptococcus neoformans have historically been
      divided into three components namely, glucuronoxylomannan (GXM),
      galactoxylomannan (GalXM), and mannoprotein (MP) but their relative spatial
      geographical relationship in the capsule is unknown.  To explore this problem
      would require the capacity for visualizing these components in the capsule. 
      Prior studies have reported serological reagents to GXM and GalXM but no
      antibodies are available against MPs.  Consequently, we immunized Balb/c mice
      with C. neoformans recombinant mannoprotein 98 and recovered twelve monoclonal
      antibodies (mAbs) of which one, an IgG2a designated 18F2, bound to intact cells
      by immunofluorescence. mAb 18F2 bound to the cell wall surface in acapsular and
      encapsulated cells.  Using mAb 18F2 and previously generated antibodies to GXM
      and GalXM we have established the localization of three capsular components GXM,
      GalXM and one type of mannoprotein, MP98 on the C. neoformans cell.  The results
      show that MP98, like GalXM, is found near the cell wall and this information
      allows us to begin to discern the geography of the cryptococcal capsule.

PMID- 21178498
TI  - Anchoring the type VI secretion system to the peptidoglycan: TssL, TagL, TagP...
      what else?
AB  - The recently identified bacterial type VI secretion system (T6SS) has rapidly
      become one of the most interesting areas of research in microbiology. In a
      relatively short period of time the relationship between the T6SS and the
      bacteriophage T4 tail and baseplate has been established. However, a number of
      questions concerning the T6SS remain the focus of a large number of researchers
      worldwide. Key questions that need to be addressed include how this system
      assembles in the cell envelope and the mechanism by which it translocates
      effector proteins across two membranes, the identification of such effectors and
      their function, how this secretion system contributes to virulence,
      interbacterial interactions and/or adaptation to the environment, and the
      evolutionary relationship between T6SS machine and bacteriophage T4. Focused on
      how the proteins constituting the secretion system interact, we recently
      identified a sub-complex of the T6SS comprised of four cell envelope proteins:
      the inner membrane-anchored TssL, TssM and TagL proteins and the outer membrane
      associated TssJ lipoprotein. We further demonstrated that the TagL subunit
      carries a specific domain allowing anchorage of the secretion system to the
      peptidoglycan (PG) layer. Herein, we discuss these results, examine whether PG
      binding motifs are found within other T6SS subunits and express hypotheses
      regarding the role of PG-binding motifs in type VI secretion.

PMID- 21178499
TI  - The genome of the amoeba symbiont "Candidatus Amoebophilus asiaticus" encodes an
      afp-like prophage possibly used for protein secretion.
AB  - The recently sequenced genome of the obligate intracellular amoeba symbiont
      'Candidatus Amoebophilus asiaticus' is unique among prokaryotic genomes due to
      its extremely large fraction of genes encoding proteins harboring eukaryotic
      domains such as ankyrin-repeats, TPR/SEL1 repeats, leucine-rich repeats, as well
      as F- and U-box domains, most of which likely serve in the interaction with the
      amoeba host. Here we provide evidence for the presence of additional proteins
      which are presumably presented extracellularly and should thus also be important
      for host cell interaction. Surprisingly, we did not find homologues of any of the
      well-known protein secretion systems required to translocate effector proteins
      into the host cell in the A. asiaticus genome, and the type six secretion systems
      seems to be incomplete. Here we describe the presence of a putative prophage in
      the A. asiaticus genome, which shows similarity to the antifeeding prophage from
      the insect pathogen Serratia entomophila. In S. entomophila this system is used
      to deliver toxins into insect hosts. This putative antifeeding-like prophage
      might thus represent the missing protein secretion apparatus in A. asiaticus.

PMID- 21178500
TI  - Campylobacter jejuni free oligosaccharides: function and fate.
AB  - The Campylobacter jejuni N-linked protein glycosylation pathway produces a
      heptasaccharide that is added to >65 periplasmic and membrane proteins and is
      also released into the periplasm as the free oligosaccharide (fOS). The fOS is a
      novel soluble component of the C. jejuni periplasmic space that exists in 10-fold
      greater quantities than its asparagine-linked counterpart. Structurally, fOS is
      the same heptasaccharide that is found attached to asparagine residues on C.
      jejuni glycoproteins and both glycans are cleaved from the
      undecaprenylpyrophosphate anchor by the previously identified
      oligosaccharyltransferase PglB, which we have now shown to be a bifunctional
      enzyme also displaying hydrolase activity. The fOS levels in C. jejuni, similar
      to bacterial periplasmic glucans, can be manipulated by altering the salt and
      osmolyte concentrations in the growth environment. Here, we outline potential
      functions of fOS and raise new questions about the underlying mechanism involved
      in PglB-mediated fOS release from its lipid anchor and fOS retention within the
      C. jejuni periplasm.

PMID- 21178501
TI  - Beyond ergosterol: linking pH to antifungal mechanisms.
AB  - Many antifungal drugs including the highly successful azoles target the fungal
      specific sterol, ergosterol, yet the molecular identity of cellular pathways
      mediating antifungal activity remained obscure. A recent study on the requirement
      of ergosterol in vacuolar H+-ATPase (V-ATPase) function uncovered a critical role
      for ion homeostasis downstream of azole inhibition of ergosterol biosynthesis.
      Here we review the functional link between regulation of V-ATPase by fungal
      membrane lipid components and discuss contributions of V-ATPase function to
      pathogenicity. The importance of pH homeostasis in virulence highlights its
      potential as target in antifungal chemotherapy.

PMID- 21178503
TI  - Testing of herpes simplex virus for resistance to antiviral drugs.
AB  - Herpes simplex virus (HSV) infections can be treated efficiently by the
      application of antiviral compounds. Several drugs on the basis of acyclovir
      (ACV), penciclovir (PCV) and foscarnet (FOS) have been approved. Resistant viral
      isolates can be observed especially in immunocompromised patients, who are
      treated with antivirals for long time intervals. That is why methods for analysis
      of HSV resistance to antiviral drugs have to be available in virological
      laboratories. We analyzed HSV type 1 (HSV-1) and type 2 (HSV-2) isolates
      resistant to ACV for correlation between phenotypic and genotypic drug resistance
      using tetrazolium reduction assay as well as sequencing of thymidine kinase (TK)
      and DNA polymerase (pol) genes. All strains were characterized as cross-resistant
      to PCV, brivudin and susceptible to cidofovir. In addition, three sequential
      isolates were resistant to FOS. Genotypic analysis revealed high polymorphism of
      TK among HSV-1 isolates and high polymorphism of DNA pol among both HSV-1- and 2
      isolates. In nearly half of ACV-resistant strains, nucleotide insertions and
      deletions, responsible for a frameshift and the synthesis of a non-functional TK
      could be related to resistance. In the remaining strains, there were non
      synonymous nucleotide substitutions which were not known as part of gene
      polymorphism. In conclusion, for reliable interpretation of genotypic resistance,
      a database of non-synonymous mutations has to be established.

PMID- 21178502
TI  - Obesity, longevity, quality of life: alteration by dietary 2-mercaptoethanol.
AB  - Previous investigations demonstrated that optimization of murine immunological
      reactivity in tissue culture required a sulfhydryl compound; the most effective
      being 2-mercaptoethanol (2-Me). Since these reports, 2-Me was found beneficial
      for both growth/function of other cell-types in vitro, including those of other
      species, and when fed orally, it impeded and/or reversed some in situ
      physiological changes associated with aging. More recently, thiol-containing
      compounds possessing oxidation-reduction potentials weaker than 2-Me were found
      to impart beneficial effects for many other, including human, diseases. Based on
      these effects, the research herein addressed the question: What consequences
      might dietary 2-Me impart on health and disease of mice other than those
      associated with aging? The main parameters monitored over the lifetime of
      individual animals exposed to dietary 10-3 M 2-Me in their drinking water were:
      quality of life (obesity and development of recumbent, emaciated and/or cachectic
      health); longevity; and appearance of tumors. Instead of anticipated toxic
      attributes, the following unique benefits were found; mean survival of a
      moderately-lived strain (A/J) was increased 40.8%, high-fat-diet obesity was
      curtailed in C57BL/10 mice, and a goal of aging intervention protocols, namely
      preventing loss of quality of life during aging (recumbent, emaciated and/or
      cachectic) was achieved. Various mechanisms are discussed as they pertain to
      these findings.

PMID- 21178504
TI  - Longevity of SLE-prone mice increased by dietary 2-mercaptoethanol via a
      mechanism imprinted within the first 28 days of life.
AB  - In the preceding report, moderately lived-mice fed dietary 2-mercaptoethanol (2
      Me) had their life extended, whereas long-lived mice were found to have the
      quality of life improved, but not extended, and did not develop high fat-diet
      obesity. In the present report, alteration of longevity of mice prone to develop
      spontaneous, systemic lupus erythematosus (SLE) by dietary 2-Me was determined.
      NZB, NZW, (NZW x NZB) F1-hybrid, BXSB/MpJ, BXSB-Yaa+/J, MRL/MpJ and MRL/MpJ
      Faslpr mice received drinking water, without or with 2-Me at concentrations of 10
      3 or 10-2 M. Therapeutic benefit was assessed by changes in longevity. The median
      survival of MRL/MpJ males was increased from 443 to 615 days and those of (NZW x
      NZB) F1 and NZB males and females were increased approximately 2-fold. The most
      unexpected finding was that longevity of F1 males was significantly extended
      irrespective of whether dietary exposure to 2-Me was initiated at 28 days of age,
      at 50 days of age, or initiated during gestation (and then terminated at weaning-
      28 days of age). Survival of F1-hybrids in which treatment was initiated in utero
      or at 28 days of age was not significantly different, whereas if initiation was
      delayed until 50 days of age, survival was >200 days shorter. Survival of male
      MRL/MpJ-Fas lpr and BXSB/MpJ (Yaa-), two strains with genetically controlled
      accelerated SLE, was not altered by 2-Me when started at 50 days. Various
      alternatives are discussed regarding potential long-lasting mechanisms imprinted
      early in life. Even though present day treatments of rodent SLE are generally
      aimed at controlling specific immunological events, with or without survival
      benefits, or are procedures presently unsuitable for therapeutic use in humans,
      the findings presented herein seem worthy of clinical evaluation.

PMID- 21178505
TI  - Reporter enzyme fluorescence (REF) imaging and quantification of tuberculosis in
      live animals.
AB  - The slow growth rate of Mycobacterium tuberculosis hinders research progress,
      since estimating the bacterial numbers present in all experiments normally relies
      on determination of colony forming units on agar plates. M. tuberculosis colonies
      can take as long as four to six weeks to become visible. Whole animal imaging is
      an emerging technology that has broad applications in all areas of biological
      sciences, including monitoring infections. Imaging allows bacterial numbers to be
      determined in real-time for each infected animal, individually, which allows
      inter-animal variability to be observed and controlled for. Reporter enzyme
      fluorescence (REF) utilizes custom substrates that allow production of a
      fluorescent product after cleavage by a bacterial enzyme. In our recently
      published studies, we demonstrate that the enzyme beta-lactamase, a naturally
      occurring enzyme expressed by M. tuberculosis, can be used for REF. The resulting
      imaging system is the first that allows non-invasive detection of natural M.
      tuberculosis strains directly in pulmonary infected living animals. Use of REF
      for M. tuberculosis infected mice allows detection of ~104 CFU in the lungs,
      which is very sensitive. This system also displays promise for allowing rapid
      evaluation of differences in virulence strains and efficacy of therapeutics and
      vaccines. This system could be developed into a diagnostic tool for tuberculosis
      through the use of REF to identify infected tissues or other diagnostic
      specimens.

PMID- 21178506
TI  - Secretion stress and fungal pathogenesis: A new, exploitable chink in fungal
      armor?

PMID- 21178507
TI  - Toll-deficient Drosophila are resistant to infection by Pneumocystis spp.:
      additional evidence of specificity to mammalian hosts.
AB  - Pneumocystis spp. are significant pathogens in a variety of mammals. We tried to
      establish a Drosophila model of pneumocystosis using either P. murina or P.
      carinii. Whereas the pathogens were competent in susceptible mice, no infection
      could be established even in corticosteroid-treated Toll-deficient flies. This
      further substantiates the tropism described for mammalian hosts.

PMID- 21178508
TI  - BMP-2 inhibits the tumorigenicity of cancer stem cells in human osteosarcoma OS99
      1 cell line.
AB  - Previously, based on high ALDH activity, we showed that cancer stem cells (CSCs)
      could be identified as ALDH(br) cells from an aggressive human osteosarcoma OS99
      1 cell line. In this study, we evaluate the impact of BMP-2 on CSCs.Three types
      of BMP receptors were expressed in freshly sorted ALDH(br) cells. In vitro,
      growth of the sorted ALDH(br) cells was inhibited by BMP-2. Using RT-PCR
      analysis, BMP-2 was found to down-regulate the expression of embryonic stem cell
      markers Oct3/4, Nanog, and Sox-2, and up-regulate the transcription of osteogenic
      markers Runx-2 and Collagen Type I. In vivo, all animals receiving ALDH(br) cells
      treated with BMP-2 did not form significant tumors, while untreated ALDH(br)
      cells developed large tumor masses in NOD/SCID mice. Immunostaining confirmed few
      Ki-67 positive cells were present in the sections of tumor containing ALDH(br)
      cells treated with BMP-2. These results suggest that BMP-2 suppresses tumor
      growth by reducing the gene expression of tumorigenic factors and inducing the
      differentiation of CSCs in osteosarcoma. BMP-2 or BMP-2-mimetic drugs, if
      properly delivered to tumor and combined with traditional therapies, may
      therefore provide a new therapeutic option for treatment of osteosarcoma.

PMID- 21178509
TI  - Detection of ERG gene rearrangements and PTEN deletions in unsuspected prostate
      cancer of the transition zone.
AB  - To assess the incidence of ERG rearrangements and PTEN deletions in a group of
      prognostically favorable PCA tumors of the transition zone (TZ). We interrogated
      54 unsuspected PCA tumors using fluorescence in-situ hybridization for ERG
      rearrangements and PTEN deletions. ERG rearrangements were detected in 6/47
      (12.7%) cases with 4/6 (66%) occurring by deletion. PTEN deletions were detected
      in 9/47 (19.1%) cases with only 3/47 (6.4%) having both PTEN losses and ERG
      rearrangements (p = 0.07). Only ERG rearrangements were associated with higher
      tumor volume > 5% (p = 0.04); PTEN deletions showed similar trends (p = 0.06).
      None of the markers showed association with Gleason score. In conclusion,
      although TZ and peripheral zone tumors share similar molecular etiologies, they
      exhibit differences in the rates of ERG and PTEN aberrations. The differences of
      ERG and /or PTEN genetic aberrations in TZ tumors may point toward a subset of
      tumors with adverse behavior. Additional studies implementing ERG and PTEN tissue
      based FISH assays in tumors of the TZ are warranted to substantiate the potential
      clinical value of these biomarkers in the management of men with incidental PCA.

PMID- 21178510
TI  - Pituitary tumor-transforming gene 1: perspective on an apoptosis pathway.

PMID- 21178528
TI  - Monitoring of plasma creatinine and urinary gamma-glutamyl transpeptidase
      improves detection of acute kidney injury by more than 20%.
AB  - OBJECTIVES: We sought to determine how early we can detect acute kidney injury
      inpatients at intensive care unit admission by combining the use of plasma
      creatinine and urinary gamma-glutamyl transpeptidase. DESIGN: Prospective study
      including development (n = 100) and validation (n = 56) cohorts. SETTINGS:
      Intensive care unit of a university hospital. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: To determine acute kidney injury, we subtracted measured
      creatinine clearance from theoretical creatinine clearance with a 25% reduction
      signifying acute kidney injury. Its incidence in 100 consecutive patients was
      36%. An indexed urinary gamma-glutamyl transpeptidase-to-urinary creatinine ratio
      was significantly increased in the patients with acute kidney injury and did not
      correlate with plasma creatinine (p = .3). Using a predefined threshold of
      indexed urinary gamma-glutamyl transpeptidase-to-urinary creatinine ratio (>12.4
      units/mmol) and plasma creatinine (>89 MUmol/L), acute kidney injury detection
      was significantly improved, making it possible to detect 22 (22%) additional
      patients with acute kidney injury. This finding was confirmed in the validation
      group. The rates of false-positive results were 30% and 19% in the data
      development and internal validation cohorts, respectively. CONCLUSIONS: The use
      of low-cost, widely available markers (creatinine and urinary gamma-glutamyl
      transpeptidase) increases the detection of acute kidney injury. Further studies
      are needed to determine the impact on outcome with the use of these biomarkers.

PMID- 21178529
TI  - Extracorporeal membrane oxygenation to support cardiopulmonary resuscitation:
      Useful, but for whom?

PMID- 21178530
TI  - Through the magnifying glass.

PMID- 21178531
TI  - The meaning of do-not-resuscitation orders: A need for clarity.

PMID- 21178532
TI  - The 'take home message' from the 'Take Heart America' program: Strengthen the
      chain!

PMID- 21178533
TI  - Small steps in the right direction for ventilator-induced lung injury:
      Prevention, prevention, prevention!

PMID- 21178534
TI  - Smoke signals in the intensive care unit.

PMID- 21178535
TI  - Measuring the effect of inappropriate initial antibiotic therapy on outcomes of
      patients with Gram-negative sepsis: An imprecise science.

PMID- 21178536
TI  - Identification of acute kidney injury.

PMID- 21178537
TI  - Refining the use of therapeutic hypothermia after cardiac arrest.

PMID- 21178538
TI  - Monitoring the ill: Is this another measurement or will it change outcomes?

PMID- 21178539
TI  - Drug therapy for sustained ventricular arrhythmias complicating acute myocardial
      infarction: What does the crystal ball tell you?

PMID- 21178540
TI  - Mild therapeutic hypothermia after cardiac arrest: Keep on chilling.

PMID- 21178541
TI  - Biomarkers of acute respiratory distress syndrome: Do good things lie nearby?

PMID- 21178542
TI  - Introducing automated acute lung injury/acute respiratory distress syndrome
      electronic screening in intensive care unit practice: Is it the future?

PMID- 21178543
TI  - Time-dependent glycemic variability and mortality in critically ill patients with
      diabetes.

PMID- 21178544
TI  - Mirror, mirror on the wall: Which is the best vasopressin receptor of them all?

PMID- 21178545
TI  - The present is pregnant with the future.

PMID- 21178546
TI  - Albumin and brain injury: Time for a new approach?

PMID- 21178547
TI  - Pediatric patients with out-of hospital cardiac arrest: Is therapeutic
      hypothermia for them?

PMID- 21178548
TI  - On pediatric delirium and the use of the Pediatric Confusion Assessment Method
      for the Intensive Care Unit.

PMID- 21178549
TI  - No sadder sight.

PMID- 21178551
TI  - The law's impact on the resolution of end-of-life conflicts in the intensive care
      unit.

PMID- 21178553
TI  - May frequency of blood glucose measurement be blurring the association between
      mean absolute glucose change per hour and mortality?

PMID- 21178555
TI  - Evidence-based support for prolonged glucocorticoid treatment in acute lung
      injury/acute respiratory distress syndrome.

PMID- 21178556
TI  - Reference values for noninvasive cardiac output monitoring in children.

PMID- 21178559
TI  - The importance of non-Acinetobacter organisms.

PMID- 21178560
TI  - Hypocapnia and the injured brain: Evidence for harm.

PMID- 21178562
TI  - Acute hepatitis C infection in HIV-positive patients.
AB  - PURPOSE OF REVIEW: For 10 years now, we have been observing an epidemic of acute
      hepatitis C (AHC) infections among HIV-positive men who have sex with men. First
      outbreaks have been observed in Europe with recent epidemics also in the United
      States and Australia. Even though randomized controlled studies on the best
      management of AHC infections in HIV-positive individuals are still lacking,
      published data on clinical studies and cohort studies allow to give guidance on
      epidemiological trends, natural course and treatment of these patients. RECENT
      FINDINGS: Observational data suggest that the early course of hepatitis C virus
      (HCV) RNA in the first 4 weeks after diagnosis may help to predict the natural
      course of AHC infections in HIV-infected patients. Starting antiviral therapy
      within 24 weeks after diagnosis yielded high response rates of 60-80%, regardless
      of HCV genotype. Pegylated interferon in combination with weight-adapted
      ribavirin is recommended for all HCV genotypes, though data on the added value of
      ribavirin are limited. SUMMARY: Prevention efforts need to be refocused in order
      to help contain the current epidemic. Regular screening will help to diagnose AHC
      infections and allow timely monitoring of the natural course and access to early
      antiviral therapy if needed.

PMID- 21178563
TI  - Current world literature.

PMID- 21178565
TI  - Utility of SLAB software as an instructional tool for spatial hearing.

PMID- 21178568
TI  - The effect of priming on release from informational masking is equivalent for
      younger and older adults.
AB  - OBJECTIVE: Previous studies have shown that presenting younger listeners with all
      but the last word of a target anomalous sentence immediately before presenting
      the full sentence in a noisy background produces a greater release from masking
      when the masker is two-talker anomalous speech than when it is speech-spectrum
      noise, thereby demonstrating that an auditory prime can produce a release from
      informational masking. The purpose of this study was to investigate whether older
      adults could gain the same benefit from auditory primes as younger adults and
      what bottom-up auditory factors contribute to the advantage provided by auditory
      primes in releasing speech from informational masking. DESIGN: A total of 76
      younger adults (university students) and 76 older adults (volunteers from the
      local community) participated in this study. All participants spoke English as a
      first language and had normal hearing below 4 kHz. RESULTS: In experiment 1,
      younger adults performed better in the presence of the speech masker, whereas
      older adults performed equivalently under both types of masking, but auditory
      priming produced an equivalent amount of release from informational masking in
      both younger and older adults. To examine the degree to which familiarity with
      the target talker's voice contributed to the priming effects observed in the
      first experiment, in experiment 2, we primed individuals with sentences that were
      spoken by the target talker but with lexical content that was unrelated to the
      target sentences. There was no release from informational masking for either age
      group. Next, to investigate the extent to which the release from informational
      masking in the first experiment was due to the amplitude envelope cues provided
      by the prime, in experiment 3, we noise vocoded the prime (using 3 bands) to
      remove semantic content while retaining some cues about the prime's amplitude
      envelope. When the primes were noise vocoded, there was no release from
      informational masking for either younger or older adults. Finally, to examine
      whether older adults' performance in the presence of the speech masker in the
      first experiment was due to an age-related decline in the ability to take
      advantage of dips in the amplitude envelope of the speech masker, in experiment
      4, we noise vocoded the speech masker. We found a significant improvement in
      performance, but the amount of improvement was equivalent for both age groups.
      CONCLUSIONS: Auditory priming resulted in equivalent amounts of release from
      informational masking in both younger and older adults. The benefit provided by
      auditory primes was not due to cues provided in the prime about the target
      talker's voice or cues provided in the prime about fluctuations in the amplitude
      envelope of the target sentences. Importantly, there was an age-related decline
      in performance in the presence of a two-talker masker relative to a continuous
      speech-spectrum noise masker; however, this age-related decline in performance
      cannot be attributed to age-related differences in the ability to take advantage
      of fluctuations in the amplitude envelope of the speech masker.

PMID- 21178567
TI  - Comparison of bimodal and bilateral cochlear implant users on speech recognition
      with competing talker, music perception, affective prosody discrimination, and
      talker identification.
AB  - OBJECTIVES: Despite excellent performance in speech recognition in quiet, most
      cochlear implant users have great difficulty with speech recognition in noise,
      music perception, identifying tone of voice, and discriminating different
      talkers. This may be partly due to the pitch coding in cochlear implant speech
      processing. Most current speech processing strategies use only the envelope
      information; the temporal fine structure is discarded. One way to improve
      electric pitch perception is to use residual acoustic hearing via a hearing aid
      on the nonimplanted ear (bimodal hearing). This study aimed to test the
      hypothesis that bimodal users would perform better than bilateral cochlear
      implant users on tasks requiring good pitch perception. DESIGN: Four pitch
      related tasks were used. 1. Hearing in Noise Test (HINT) sentences spoken by a
      male talker with a competing female, male, or child talker. 2. Montreal Battery
      of Evaluation of Amusia. This is a music test with six subtests examining pitch,
      rhythm and timing perception, and musical memory. 3. Aprosodia Battery. This has
      five subtests evaluating aspects of affective prosody and recognition of sarcasm.
      4. Talker identification using vowels spoken by 10 different talkers (three men,
      three women, two boys, and two girls). Bilateral cochlear implant users were
      chosen as the comparison group. Thirteen bimodal and 13 bilateral adult cochlear
      implant users were recruited; all had good speech perception in quiet. RESULTS:
      There were no significant differences between the mean scores of the bimodal and
      bilateral groups on any of the tests, although the bimodal group did perform
      better than the bilateral group on almost all tests. Performance on the different
      pitch-related tasks was not correlated, meaning that if a subject performed one
      task well they would not necessarily perform well on another. The correlation
      between the bimodal users' hearing threshold levels in the aided ear and their
      performance on these tasks was weak. CONCLUSIONS: Although the bimodal cochlear
      implant group performed better than the bilateral group on most parts of the four
      pitch-related tests, the differences were not statistically significant. The lack
      of correlation between test results shows that the tasks used are not simply
      providing a measure of pitch ability. Even if the bimodal users have better pitch
      perception, the real-world tasks used are reflecting more diverse skills than
      pitch. This research adds to the existing speech perception, language, and
      localization studies that show no significant difference between bimodal and
      bilateral cochlear implant users.

PMID- 21178570
TI  - Outcomes after multiple lines of chemotherapy for platinum-resistant epithelial
      cancers of the ovary, peritoneum, and fallopian tube.
AB  - BACKGROUND: Platinum-resistant and refractory cancers of the ovary, fallopian
      tube, and peritoneum have a poor prognosis, yet in some cases, they can respond
      to multiple lines of chemotherapy. Uncertainty remains over optimal drug choice
      and when therapeutic focus should be switched from active therapy to supportive
      care. METHODS: A retrospective case note review was performed on 274 women
      treated for platinum-resistant/refractory ovarian, fallopian tube, or peritoneal
      carcinoma at the Christie Hospital between 2004 and 2008. Baseline data at onset
      of platinum resistance and outcomes from subsequent lines of therapy were
      recorded. RESULTS: A total of 689 lines of therapy were administered with a
      median overall survival from initiation of first-line therapy for platinum
      resistant disease of 61 weeks. Twenty-eight percent of women commenced cytotoxic
      therapy in the last 3 months of life. Treatment efficacy declined rapidly with
      successive lines of therapy particularly if disease progression occurred during
      first-line therapy. Factors independently associated with worse overall survival
      at recognition of platinum resistance were performance status, presence of stage
      IV disease, elevated cancer antigen 125, and platinum-refractory disease.
      CONCLUSIONS: A significant proportion of women who were treated received therapy
      within the last few months of life with little clinical benefit. Disease
      progression on 2 consecutive lines of therapy should be used as a guide to
      discontinue cytotoxic treatment. A subset of patients with poor prognosis at the
      onset of platinum resistance, who may have little gain from anticancer treatment,
      can be identified.

PMID- 21178571
TI  - Neoadjuvant chemotherapy is associated with prolonged primary treatment intervals
      in patients with advanced epithelial ovarian cancer.
AB  - BACKGROUND: We evaluated the impact of neoadjuvant chemotherapy (NC) relative to
      primary surgery (PS) to determine if there was a difference in the total time and
      number of chemotherapy cycles given in patients with advanced epithelial ovarian
      cancer. METHODS: We identified 263 consecutive women meeting eligibility from
      1993 to 2005 for this institutional review board-approved study. Eligible
      patients in this analysis were those women with advanced disease (stage IIIC-IV)
      in whom a maximal cytoreductive effort was planned either at PS or after NC. Time
      to start chemotherapy was defined as follows: (1) NC group: confirmation of
      diagnosis through biopsy, cytological diagnosis from ascites, and pleural
      effusion; (2) PS group: confirmation of diagnosis from the date of surgery that
      confirmed the diagnosis of epithelial ovarian cancer. Total chemotherapy cycles:
      (1) NC group: NC chemotherapy cycles plus postoperative cycles; (2) PS group:
      chemotherapy after primary tumor debulking surgery. Clinical information
      evaluated included chemotherapy type, chemotherapy cycle number, total time to
      administer frontline chemotherapy, and survival. RESULTS: Median chemotherapy
      cycles were greater in the NC group compared with the PS group (9 [range, 4-30]
      vs 6 [range, 3-19]; P < 0.01). The PS group was also more likely to undergo
      chemotherapy regimens involving platinum and taxane treatment compared with the
      NC group (79% vs 65%; P = 0.017). Total time undergoing primary chemotherapy from
      initial diagnosis was greater in the NC group compared with PS (223 vs 151 days;
      P < 0.01). No significant difference was observed in overall survival and
      progression-free survival in the 2 groups. CONCLUSIONS: In patients with advanced
      ovarian cancer, NC followed by abdominal hysterectomy is associated with improved
      perioperative outcomes including optimal cytoreduction, decreased blood loss, and
      decreased inpatient hospitalization. In this cohort, NC was also associated with
      prolonged chemotherapy treatment intervals and increased chemotherapy cycles
      without improvement in survival.

PMID- 21178572
TI  - Prolonged conservative treatment of endometrial cancer patients: more than 1
      pregnancy can be achieved.
AB  - BACKGROUND: Preserving reproductive function in young patients with early
      endometrial cancer is an accepted concept today. The safety and feasibility of
      long-term conservative treatment, allowing more than 1 pregnancy, remain to be
      ascertained. METHODS: This study was a retrospective chart review of a 27 women
      with endometrioid adenocarcinoma of the endometrium, who were treated
      conservatively at 2 tertiary-care institutions. Treatment comprised oral high
      dose progestins with or without a levonorgestrel-releasing intrauterine device.
      Endometrial biopsy was repeated every 2 to 3 months. RESULTS: Over 7.8 to 412
      months (median, 57.4 months), tumors regressed completely in 24 (89%) of 27
      patients and partially in 2 patients, with 79% responding within 1 to 17 months.
      Of the complete responders, 15 (62%) of 24 had a recurrence; 4 underwent
      hysterectomy, and 11 underwent subsequent progestational treatment. All 11
      responded, and 3 subsequently conceived. After 2 to 4 years, 5 patients again had
      a recurrence, of whom 3 underwent hysterectomy. Overall, 2 patients developed
      ovarian adenocarcinoma. All patients are currently disease-free. Conception
      occurred in 14 (51.8%) of 27 patients, in 5 more than once. There were 17 live
      births, and 2 patients are pregnant. CONCLUSIONS: According to our data,
      prolonged progestational therapy for early-stage endometrial adenocarcinoma,
      allowing women to conceive, is feasible and apparently does not alter clinical
      outcome. Patients should be advised of the high recurrence rate and possible
      concomitant ovarian malignancy.

PMID- 21178573
TI  - Recovery issues of fertility-preserving surgery in patients with early-stage
      cervical cancer and a model for survivorship: the physician checklist.
AB  - INTRODUCTION: To present a qualitative data analysis of items exploring the
      treatment, adjustment, and recovery of 33 patients who underwent radical
      trachelectomy (RT), and to determine the feasibility of using a physician
      checklist (PCL) as a model for survivorship assessment. METHODS: This prospective
      study was approved by the Memorial Sloan-Kettering Cancer Center's Institutional
      Review Board. Participants completed a survey including exploratory items focused
      on fertility issues and reproductive concerns, treatment, adjustment, and
      recovery over 2 years. All responses to the exploratory questions were
      transcribed verbatim; thematic analysis was used to identify, evaluate, and show
      patterns within the data set; and descriptive statistics were calculated for
      thematic categories. A limited waiver of authorization was obtained for medical
      chart review of these patients (who underwent RT) for 2 years before (January
      2006 to December 2007) and 2 years after (January 2008 to December 2009)
      implementation of the checklist to evaluate its feasibility. RESULTS: In response
      to "how successful you feel you will be at conceiving in the future?" on a scale
      of 0% to 100%, scores ranged from 54% to 60%. Approximately 70% of the patients
      reported concerns about conceiving; however, these lessened with time-88% at 6
      months to 73% at 24 months. Six percent of women were trying to conceive by 12
      months; this increased to 21% by 24 months. Five primary themes emerged from the
      qualitative analysis that were found to be prevalent across all exploratory items
      inquiring about difficulties or the hardest adjustment to treatment, recovery,
      and problems associated with RT; these included menstrual/vaginal issues,
      emotional impact, life interruptions/return to normalcy, general pain, and
      recovery process. The PCL identified higher rates of neocervical stenosis (58%),
      encroachment (54%), vaginal scarring (50%), and dyspareunia (33%) than medical
      charts, and increased documentation of reproductive consults (54%) and assistance
      (21%). CONCLUSION: Global themes expressed by our patients are consistent with
      those of other cancer survivors. The PCL is an excellent supplement to medical
      charts by documenting important survivorship issues.

PMID- 21178574
TI  - Outcomes of patients undergoing radical hysterectomy for cervical cancer of high
      risk histological subtypes.
AB  - BACKGROUND: The most common types of cervical cancer are squamous cell carcinoma,
      adenocarcinoma, and adenosquamous carcinoma, referred to here collectively as SA
      cervical cancer. Other types of cervical cancer, referred to here collectively as
      nonsquamous/nonadenocarcinoma (NSNA) cervical cancer, include neuroendocrine,
      small cell, clear cell, sarcomatoid, and serous tumors. Anecdotally, NSNA tumors
      seem to have a worse prognosis than their SA counterparts. We sought to determine
      whether patients with early-stage NSNA have a worse prognosis than those with
      early-stage SA cervical cancer. METHODS: We retrospectively reviewed charts of
      women with stage IA1-IB2 NSNA cervical cancer treated by radical hysterectomy and
      lymph node staging at M. D. Anderson Cancer Center from 1990 to 2006. The NSNA
      patients were matched 1:2 to patients with grade 3 SA lesions on the basis of
      stage, age at diagnosis, tumor size, and date of diagnosis. RESULTS: Eighteen
      patients with NSNA primary cervical cancer subtypes (neuroendocrine [n = 7],
      small cell [n = 5], clear cell [n = 4], papillary serous [n = 1], and sarcomatoid
      [n = 1]) were matched to 36 patients with grade 3 SA lesions. There were no
      differences between the 2 groups in age, body mass index, clinical stage, or
      lesion size. The 2 groups also did not differ with respect to number of nodes
      resected, lymphovascular space invasion, margin status, lymph node metastasis, or
      adjuvant radiation therapy or chemotherapy. At a median follow-up of 44 months,
      median progression-free and overall survivals had not been reached; however, both
      progression-free survival (P = 0.018) and overall survival (P = 0.028) were worse
      for the NSNA group. The 5-year progression-free and overall survival rates were
      61.2% and 67.6%, respectively, for the NSNA group, compared with 90.1% and 88.3%,
      respectively, for the SA group. CONCLUSIONS: Patients with early-stage NSNA
      cervical cancer undergoing radical hysterectomy and pelvic lymphadenectomy have a
      worse prognosis than patients with grade 3 SA lesions. Patients with NSNA tumors
      may require a multimodality approach to their cancer care.

PMID- 21178575
TI  - Neoadjuvant chemotherapy followed by radical vaginal trachelectomy and adjuvant
      chemotherapy for clear cell cancer of the cervix: a feasible approach and review.
AB  - BACKGROUND: Clear cell adenocarcinoma of the cervix (CCAC) may affect pediatric
      and younger women in absence of diethylstilbestrol exposure and other classic
      predisposing factors for cervical cancer. Prognosis is similar for early-stage
      CCAC, squamous cell cancer and non-clear cell adenocarcinoma of the cervix.
      Vaginal radical trachelectomy (VRT) and abdominal radical trachelectomy (ART)
      with pelvic lymph node dissection have evolved as valuable fertility-preserving
      treatment options. Neoadjuvant chemotherapy (NACT) before abdominal radical
      trachelectomy/VRT may reduce tumor size and thereby facilitate surgery. In some
      cases, adjuvant treatment in the presence of high-risk prognostic features may be
      required to optimize treatment. METHODS: A 13-year-old adolescent with
      International Federation of Obstetrics and Gynecology stage IB1 CCAC was treated
      with NACT using carboplatin and paclitaxel (CP) followed by laparoscopic pelvic
      lymphadenectomy, VRT, and adjuvant chemotherapy. RESULTS: Neoadjuvant
      chemotherapy using CP was well tolerated with no toxicity. Neoadjuvant
      chemotherapy reduced the tumor size and facilitated radical vaginal
      trachelectomy. Adjuvant treatment was recommended in the presence of risk
      factors. The patient elected to conserve the uterus and underwent 3 further
      cycles of adjuvant chemotherapy with CP. CONCLUSIONS: This is the first reported
      case of CCAC treated with NACT using CP followed by laparoscopic pelvic
      lymphadenectomy, VRT, and adjuvant chemotherapy. A successful treatment outcome
      achieved using this novel approach suggests its applicability in selected cases.

PMID- 21178576
TI  - What do women with gestational trophoblastic disease understand about the
      condition?
AB  - INTRODUCTION: Little is known about patients' understanding of the causes,
      treatments, and implications of gestational trophoblastic disease (GTD). Clinical
      observation suggests that such health literacy is limited. We report on the
      perceptions of causes and treatment of GTD and its impact on fertility and
      reproductive outcomes. METHODS: Cross-sectional analysis of 176 Australian women
      previously diagnosed with GTD (no longer receiving follow-up/treatment) recruited
      from a state-wide registry. Participants comprised 149 (85%) women with GTD who
      did not require chemotherapy and 27 (15%) women who required chemotherapy for
      malignancy or persistent molar disease. Data were collected from medical records
      and via self-report questionnaire. RESULTS: Participants were 94 women (53%) with
      partial mole, 75 (43%) with complete mole, 4 (2%) with choriocarcinoma, and 3
      (2%) with hydatidiform mole not otherwise specified. Mean (SD) age at diagnosis
      and time since diagnosis were 32.1 (6.3) and 4.7 (3.3) years, respectively.
      Chance/bad luck was the most endorsed cause (n = 146, 83%); 23 (13%) thought GTD
      was hereditary and 10 (6%) identified a chromosomal etiology. Between 24% and 32%
      were unsure of the role of alcohol/drugs, venereal diseases, smoking, pollution,
      contraceptives, and lowered immunity. Surgical/medical procedure (n = 127, 72%)
      and healthy diet (n = 53, 30%) were the most endorsed treatments. Between 18% and
      23% were unsure of the treatment effectiveness of diet, vitamins, exercise,
      complementary therapy, and contraception. All women treated with chemotherapy
      understood the rationale thereof; 23 (85%) perceived chemotherapy to be
      successful, and 19 (70%) could name the agent. Few women perceived a negative
      impact on their fertility (n = 28, 16%); 52 (30%) were reluctant to conceive
      again and 100 (57%) questioned their ability to have healthy children. After
      diagnosis, 111 (63%) had at least 1 live birth. CONCLUSIONS: Notwithstanding
      limitations, this study is the largest of its type to date. These descriptive
      data enhance our understanding of patients' experience on GTD, highlight the
      scope of GTD health literacy, and may be useful for clinicians to adjust the
      content of their patient education.

PMID- 21178577
TI  - Role of robot-assisted surgery in cervical cancer.
AB  - BACKGROUND: The development of robotic technology has facilitated the application
      of minimally invasive techniques for complex operations in gynecologic oncology.
      OBJECTIVES: The objective of the study was to assess and summarize the current
      literature on the role of robot-assisted surgery in cervical cancer in terms of
      its utility and outcome. METHODS: Literature review concerning the use of robot
      assisted technology in the management of cervical cancer, including radical
      hysterectomy, trachelectomy, parametrectomy, pelvic and aortic lymphadenectomy,
      and pelvic exenteration, was performed. RESULTS: To date, 12 articles addressing
      radical hysterectomy, 5 articles of radical trachelectomy, and 6 articles of
      surgical procedure in advanced or recurrent cervical cancer, all performed
      robotically, are published in the literature. The advantages of the robotic
      system include 3-dimensional vision, tremor reduction, motion downscaling,
      improved ergonomics, and greater dexterity with instrument articulation. Because
      of these benefits, the robotic technology seems to facilitate the surgical
      approach for technically challenging operations performed to treat primary, early
      or advanced, and recurrent cervical cancer as evidenced by the current
      literature. CONCLUSIONS: Surgical management of cervical cancer may be one of the
      gynecologic oncology surgeries that can take full advantage of robotic assistance
      in a minimally invasive manner. Continued research and clinical trials are needed
      to further elucidate the equivalence or superiority of robot-assisted surgery to
      conventional methods in terms of oncological outcome and patient's quality of
      life.

PMID- 21178578
TI  - Summary of gynecologic pathology papers with significant clinical implications
      from the last United States and Canadian Academy of Pathology, Boston, March
      2009.
AB  - At the last United States and Canadian Academy of Pathology meeting, there was a
      total of 171 papers presented in the gynecologic pathology sessions. I have
      prepared a summary of some papers that I consider interesting and provides new
      information for gynecologic oncologists. In some of these studies, I have also
      incorporated additional comments.

PMID- 21178579
TI  - A case of H syndrome showing immunophenotye similarities to Rosai-Dorfman
      disease.
AB  - H syndrome (OMIM 612391) is a recently described autosomal recessive
      genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic
      skin and systemic manifestations including hepatosplenomegaly, cardiac anomalies,
      hearing loss, hypogonadism, low height, hypertriglyceridemia, hallux valgus, and
      flexion contractures. H syndrome results from mutations in the SLC29A3 gene,
      which encodes the human equilibrative nucleoside transporter hENT3. The cutaneous
      histopathology is characterized by a striking mononuclear cell infiltrate in the
      dermis consisting of CD68+ monocyte-derived cells and CD34+ and factor XIIIa+
      dendrocytes. We describe a case of H syndrome in which the infiltrating
      mononuclear cells were CD68+, CD163+, S-100+, and CD1a-, thus simulating the
      immunophenotype observed in Rosai-Dorfman disease (RDD). The immunostaining for
      CD21, fascin, and CD34 were negative, and there were also many factor XIIIa+
      dendrocytes interspersed within the dense mononuclear cell infiltrate. Recent
      findings of biallelic mutations in SLC29A3 in 2 families reported to have
      familial RDD and in a kindred with Faisalabad histiocytosis (OMIM 602782), which
      is an autosomal inherited form of histiocytosis with similarities to RDD, may
      explain the RDD-like immunophenotype in our H syndrome case.

PMID- 21178580
TI  - Cutaneous adenolipoma: extending the spectrum of changes in the lipomatous and
      epithelial components.
AB  - Adenolipoma refers to a variant of a lipoma with entrapped eccrine or, rarely,
      apocrine units. We present 5 cases of cutaneous adenolipoma to demonstrate the
      spectrum of changes in the lipomatous and epithelial components. The cases
      include 3 lesions having a conventional lipomatous element and 1 with a spindle
      cell lipomatous component, each additionally featuring entrapped minimally
      altered eccrine units. In the remaining case, the epithelial component manifested
      a combination of hyperplastic and metaplastic changes (clear cell and squamous
      metaplasia) and unusually altered polarity of luminal cells with expression of
      myoepithelial cell markers on the luminal cells while focal absence of
      basal/myoepithelial cell in the corresponding area as evident microscopically and
      immunohistochemically.

PMID- 21178581
TI  - Epidermal basaloid cell hyperplasia overlying dermatofibromas.
AB  - In a series of 1117 dermatofibromas (69% women and 31% men), there were 25 cases
      (2.2%) with basaloid cell hyperplasia (BCH) of the overlying epidermis. This type
      of hyperplasia, which closely resembled a basal cell carcinoma (BCC), was
      predominantly seen in men (14 vs. 11 cases). To determine the nature of these
      BCHs, we applied a panel of 18 antibodies that are commonly used to classify
      epithelial proliferations on 6 cases with sufficient amounts of BCH and on 20
      BCCs of various types. The number of CK20-positive Merkel cells was found to be
      increased in 4 cases of BCH, whereas these cells were completely absent or
      reduced in all BCCs. The significance of this finding must be interpreted with
      caution, but it must be regarded as a promising method to distinguish between
      reactive BCHs and neoplastic BCCs. Except for this rather subtle finding, none of
      the antibodies used could discriminate between the 2 conditions.

PMID- 21178582
TI  - Dermabrasion in acquired melanocytic nevi: a histopathological and
      immunohistochemical study.
AB  - INTRODUCTION: When subjected to trauma, acquired melanocytic nevi may present
      atypical histological features similar to alterations that occur after exposure
      to ultraviolet radiation. These persist for up to 3 weeks. To date, no study has
      evaluated the alterations that occur after dermabrasion in acquired melanocytic
      nevi. OBJECTIVE: To evaluate the histopathological and immunohistochemical
      alterations those occur in acquired melanocytic nevi, 4 weeks after dermabrasion.
      MATERIALS AND METHODS: This study evaluated 50 acquired melanocytic nevi, in
      which half of each lesion was submitted to dermabrasion, leaving the other half
      intact, and compared the histopathological and immunohistochemical findings from
      the 2 sides 4 weeks after the procedure. RESULTS: Five acquired melanocytic nevi
      were from male and 45 from female patients. The age of the patients varied from
      15 to 69 years. On the dermabraded side, there was a greater frequency of
      atypical melanocytes (P = 0.015), increase in relation to nucleus/cytoplasm of
      the melanocytes (P = 0.034); inflammatory infiltrate (P = 0.007); and
      neovascularization (P = 0.004). In the immunohistochemical evaluation, there was
      a significantly higher percentage of immunoreactive melanocytes on this side for
      the HMB-45 only in the junctional component (P = 0.001) and for Ki-67, at a low
      rate, in the dermis (P = 0.03). CONCLUSIONS: Four weeks after the dermabrasion,
      atypical features, such as melanocytic atypia and pagetoid spread remained.
      Although these alterations may simulate melanoma in situ, the association with
      features of histopathological tissue repair (inflammatory infiltrate and
      neovascularization), together with immunohistochemical findings that are
      uncharacteristic of malignancy, favors a diagnosis of a benign lesion. These
      atypical alterations persist longer than those found after ultraviolet radiation.

PMID- 21178583
TI  - NGFR (p75) expression in cutaneous scars; Further evidence for a potential
      pitfall in evaluation of reexcision scars of cutaneous neoplasms, in particular
      desmoplastic melanoma.
AB  - Desmoplastic melanoma is a rare variant of malignant melanoma composed of spindle
      cells in a collagenous matrix. The antibody against NGFR (low affinity nerve
      growth factor receptor, also known as p75) stains cells of desmoplastic melanoma
      with high sensitivity; however, the specificity of this marker is not well
      established. Although there are established histologic criteria for recognition
      of desmoplastic melanoma, the evaluation of residual disease in cutaneous
      reexcision scars can be challenging. If residual spindle cells in scar are
      sufficiently atypical and NGFR positive, their presence could be interpreted as
      residual desmoplastic melanoma. In this study, we reevaluated the use of antibody
      against NGFR to detect residual disease in reexcision specimens of melanocytic
      neoplasms as the previously published works are contradictory. Our data indicate
      that anti-NGFR antibody stains many cells in the scar, some of which seem to be
      myofibroblasts, nerve twigs, and Schwann cells. Our findings further suggest that
      NGFR is not a suitable marker to evaluate reexcision scars for desmoplastic
      melanoma, especially as a sole marker, as its specificity is low.

PMID- 21178584
TI  - An SP1-binding site polymorphism in the COLIAI gene and osteoporosis in Egyptian
      patients with thalassemia major.
AB  - beta-Thalassemia major is an inherited blood disorder, which mainly affects the
      Mediterranean region. Osteoporosis represents an important cause of morbidity in
      beta-thalassemia major and its pathogenesis has not been completely clarified.
      Genetic factors play an important role in the pathogenesis of osteoporosis and
      several candidate gene polymorphisms have been implicated in the regulation of
      this process. A G->T polymorphism in the regulatory region of the collagen type I
      alpha 1 (COLIAI) gene at a recognition site for transcription factor Sp1 has been
      strongly associated with osteoporosis. The aim of the present study was to
      examine the distribution of COLIAI polymorphism and its relationship with bone
      mineral density (BMD) at the lumbar spine and femur in patients and controls. In
      this study, the G->T polymorphism was detected in 31 Egyptian beta-thalassemia
      major patients and 20 healthy controls and its possible association with BMD was
      investigated. Alleles S and s were detected by the presence of a G or T
      nucleotide, respectively, in a regulatory site of the COLIAI gene using
      polymerase chain reaction (PCR). A total of 80.6% of the beta-thalassemia
      patients were homozygous for G/G (SS) and 19.4% were heterozygotes for G/T (Ss)
      polymorphism. There was no ss genotype in our patients. In the control group, 70
      and 30% had SS and Ss genotypes, respectively. There was no significant
      difference between Z-score of patients with SS and Ss at head of femur (P = 1) or
      at lumbar spine (P = 0.48). Conclusion Our results raise the possibility that
      genotyping at the Sp1 site could be of clinical value in identifying the
      thalassemic patients at risk of developing osteoporosis.

PMID- 21178585
TI  - Acquired protein C deficiency in a child with acute myelogenous leukemia,
      splenic, renal, and intestinal infarction.
AB  - We report the case of a 6-year-old boy diagnosed with acute promyelocytic
      leukemia (AML-M3V) when he presented with pallor, abdominal pain, anorexia, and
      fatigue. Induction chemotherapy was started according to the AML-BFM 98 protocol
      along with Vesanoid (ATRA, All-trans retinoic acid). On the sixth day of
      induction, he developed splenic and gallbladder infarcts. Splenectomy and
      cholecystectomy were performed while chemotherapy induction continued as
      scheduled. Four days later, he developed ischemic areas in the kidneys and
      ischemic colitis in the sigmoid colon. Hypercoagulation studies showed severe
      deficiency of protein C. Tests showed protein C 16% (reference range 70-140%),
      protein S 87% (reference range 70-140%), antithrombin III 122% (reference range
      80-120%), prothrombin time 13.6 s (reference = 11.3), INR (international
      normalized ratio) 1.21, partial thromboplastin time 33 s (reference = 33),
      fibrinogen 214 mg/dl, D-dimer 970 MUg/ml, factor II 98%, and that antinuclear
      antibody, antiphospholipid antibodies, mutation for factor II gene (G20210A), and
      mutation for Arg506 Gln of factor V were all negative (factor V Leiden). There
      was no evidence of clinical disseminated intravascular coagulation (DIC). He was
      treated with low molecular weight heparin and did well. He continues to be in
      complete remission 7 years later with normal protein C levels. Acquired protein C
      deficiency can occur in a variety of settings and has been reported in acute
      myelocytic leukemia. However, clinically significant thrombosis in the absence of
      clinical DIC, such as our case, remains extremely rare.

PMID- 21178586
TI  - Diagnosis and therapeutic management in a patient with type 2B-like acquired von
      Willebrand syndrome.
AB  - Acquired von Willebrand syndrome (AVWS) usually mimics von Willebrand disease
      (VWD) type 1 or 2A. However, in rare cases, the characteristics of other VWD
      types can predominate in AVWS that might require careful consideration of
      differential treatment options. The diagnosis and the treatment of a case of type
      2B-like AVWS are discussed. Diagnosis of AVWS was ascertained by determining
      ristocetin cofactor activity, ristocetin-induced platelet aggregation, von
      Willebrand factor antigen, collagen binding and characterization of von
      Willebrand factor (VWF) multimers. Inhibitor presence was sought through mixing
      experiments, the Bethesda method, and calculation of the in-vivo recovery and
      plasma half-life of VWF after administration of factor VIII/VWF concentrate.
      Mutations in the A1 domain of VWF were ruled out by sequencing of exon 28 of the
      VWF gene. A 34-year-old male patient, putatively diagnosed with type 2B VWD, and
      undergoing laparoscopic cholecystectomy, did not respond adequately to
      perioperative hemostatic treatment with desmopressin and high doses of factor
      VIII/VWF concentrate, requiring the administration of recombinant activated
      factor VII. Further diagnostic workup revealed AVWS mimicking type 2B VWD, most
      likely owing to an autoantibody developed in the course of underlying monoclonal
      gammopathy of undetermined significance. The presence of AVWS should be
      considered before a diagnosis of type 2B VWD is made, especially in patients with
      a history atypical for inherited disease.

PMID- 21178587
TI  - Cleft lip and palate with associated digital and cardiac anomalies: a new
      dominant orofacial clefting syndrome?

PMID- 21178588
TI  - Cardiofaciocutaneous syndrome in a mother and two sons with a MEK2 mutation.

PMID- 21178589
TI  - Nightly analyses of subjective and objective (actigraphy) measures of sleep in
      fibromyalgia syndrome: what accounts for the discrepancy?
AB  - OBJECTIVES: To evaluate the concordance between the subjective and objective
      methods of sleep assessment in patients with fibromyalgia syndrome (FMS) and to
      delineate factors associated with discrepancy between the 2 sleep assessment
      methods. METHODS: Seventy-five patients with FMS completed a 7-day home
      assessment protocol. They wore an actigraphic device at all times. In the
      morning, they used the electronic diary to record the subjective report of sleep
      from the previous night and current severity of the FMS-related symptoms.
      RESULTS: On average, the 2 assessment methods yielded a 73 absolute minute
      difference per night per patient. About half of the nights, sleep duration was
      underestimated. Approximately 20% of the nights had greater than 2-hour
      difference between the 2 methods. Factors related to this large discrepancy were
      (1) objective indicator of restless sleep, (2) subjective report of difficulty
      falling asleep, and (3) report of fatigue at the time of reporting. FMS-related
      symptoms were related to subjective report of poor sleep but not to objective
      sleep data. DISCUSSION: Misestimation of sleep seems common in FMS patients,
      particularly when their sleep quality is poor. Careful considerations for
      evaluating the severity of patients' sleep complaints are critical in adequate
      management of sleep disturbance that is commonly reported by FMS patients.

PMID- 21178590
TI  - A multidimensional measure of pain interference: reliability and validity of the
      pain disability assessment scale.
AB  - OBJECTIVE: Measuring outcomes across multiple domains is essential for an
      adequate understanding of chronic pain and the effects of pain treatment. Pain
      interference reflects the negative effects of pain on functioning, and is
      recognized as a critical outcome domain. The Pain Disability Assessment Scale
      (PDAS) contains items that assess the negative effects of pain on broad spectrum
      pain interference domains. The purpose of this study was to examine the factor
      structure, reliability, and validity of the PDAS. METHODS: One hundred sixty-four
      Japanese patients with chronic pain were administered the PDAS, the Brief Pain
      Inventory, and the Hospital Anxiety and Depression Scale. RESULTS: The findings
      support a 3 factor structure of the PDAS items, as well as a high level of
      internal consistency of the scales created from these factors (Cronbach alpha's
      range: 0.87 to 0.95). Validity of the 3 scales was supported through their
      significant associations, in hypothesized directions, with measures of pain
      intensity, anxiety, depression, and another established measure of pain
      interference, as well as differences in PDAS scores between patients with versus
      without back pain. CONCLUSIONS: The PDAS may be useful when researchers or
      clinicians require a multidimensional measure of the effects of pain on a
      patient's life.

PMID- 21178591
TI  - Treatment expectation for pain coping skills training: relationship to
      osteoarthritis patients' baseline psychosocial characteristics.
AB  - OBJECTIVES: This study examined predictors of treatment expectation among
      osteoarthritis (OA) patients in a multisite clinical trial of pain coping skills
      training (CST). METHODS: Patients (N=171) completed a pretreatment assessment
      battery that asked questions about treatment expectations, pain coping variables,
      pain, physical function, psychological distress, quality of life, and depression
      as well as background demographic and medical variables. RESULTS: Regression
      analyses indicated that several variables accounted for 21% of the variance in
      treatment expectations (P<0.0001). Patients who were classified as adaptive
      copers, reported higher self-efficacy and social interaction, had higher quality
      of life, and who had lower levels of affective distress and depression had more
      positive expectations about engaging in pain CST. Variables that were not
      associated with treatment expectation were level of pain and physical
      dysfunction, duration of disease, and disability status as well as demographic
      variables. DISCUSSION: Although many OA patients will approach pain CST with
      positive expectations, others have lower expectations. This study suggests that a
      multidimensional assessment of OA patients with chronic pain can identify those
      who have higher expectations versus lower expectations. The results suggest that
      patients who are psychologically distressed are less optimistic about engaging in
      treatment and that these patients, in particular, may benefit from and need
      pretreatment motivational interviewing to enhance their uptake of pain coping
      skills.

PMID- 21178592
TI  - Local pain and spreading hyperalgesia induced by intramuscular injection of nerve
      growth factor are not reduced by local anesthesia of the muscle.
AB  - OBJECTIVES: Injections with local anesthesia for therapeutic and diagnostic
      purposes are common clinical practice. This double-blind placebo controlled study
      explores the rational of local anesthetic blocks for the detection of muscle pain
      as the primary generator in spreading hyperalgesic conditions. METHODS:
      Experimental muscle pain was induced by injections of nerve growth factor (NGF)
      in the left and right supraspinatus muscle of 11 healthy volunteers. One day
      later ropivacaine and saline were administered with ultrasound guidance in the
      left or right supraspinatus muscle in a randomized double-blind manner.
      Assessments before NGF, day 1 (before and after ropivacaine/saline), and day 7
      included: visual analog scale (VAS) pain scores at rest and during shoulder
      shrugging, time until exercise interruption owing to pain, cutaneous pain
      sensitivity, pressure pain thresholds, and pain VAS during tonic pressure
      stimulation. Cutaneous and pressure pain sensitivity were assessed over the
      supraspinatus, infraspinatus, and deltoideus muscles, and at the web space
      between first and second finger. RESULTS: Increased VAS pain scores and increased
      pressure pain sensitivity of the supraspinatus and infraspinatus muscles were
      found in both sides one day after the NGF injection compared with baseline. One
      day after NGF injections, the time until participants stopped exercising was
      reduced compared with baseline. The increased muscle pain sensitivity was not
      normalized by intramuscular ropivacaine. Saline caused increased VAS pain scores
      compared with ropivacaine. DISCUSSION: Muscle pain and spreading hyperalgesia
      induced by NGF is maintained despite anesthesia of the primary nociceptive locus.
      This indicates that intramuscular injection of local anesthetics may not be a
      valid diagnostic method for primary muscle pain.

PMID- 21178593
TI  - Temporomandibular disorders and associated clinical comorbidities.
AB  - OBJECTIVE: Temporomandibular joint and muscle disorders (TMJD) are ill-defined,
      painful debilitating disorders. This study was undertaken to identify the
      spectrum of clinical manifestations based on self-report from affected patients.
      METHODS: A total of 1511 TMJD-affected individuals were recruited through the web
      based registry of patients maintained by The TMJ Association, Ltd, a patient
      advocacy organization, and participated in the survey as well as 57 of their
      nonaffected friends. Results were also compared with US population for questions
      in common with the National Health and Nutrition Examination Survey. RESULTS: The
      TMJD-affected individuals were on average 41 years of age and predominantly
      female (90%). Nearly 60% of both men and women reported recent pain of moderate
      to-severe intensity with a quarter of them indicating interference or termination
      of work-related activities. In the case-control comparison, a higher frequency of
      headaches, allergies, depression, fatigue, degenerative arthritis, fibromyalgia,
      autoimmune disorders, sleep apnea, and gastrointestinal complaints were prevalent
      among those affected with TMJD. Many of the associated comorbid conditions were
      over 6 times more likely to occur after TMJD was diagnosed. Among a wide array of
      treatments used (46 listed), the most effective relief for most affected
      individuals (91%) was the use of thermal therapies--hot/cold packs to the jaw
      area or hot baths. Nearly 40% of individuals affected with TMJD patients reported
      one or more surgical procedures and nearly all were treated with one or many
      different medications. Results of these treatments were generally equivocal.
      Although potentially limited to the most severe TMJD affected individuals, the
      survey results provide a comprehensive dataset describing the clinical
      manifestations of TMJD. DISCUSSION: The data provide evidence that TMJD represent
      a spectrum of disorders with varying pathophysiologies, clinical manifestations,
      and associated comorbid conditions. The findings underscore the complex nature of
      TMJD, the need for more extensive interdisciplinary basic and clinical research,
      and the development of outcome-based strategies to more effectively diagnose,
      prevent, and treat these chronic, debilitating conditions.

PMID- 21178594
TI  - Ondansetron, a 5HT3-antagonist, does not alter dynamic mechanical allodynia or
      spontaneous ongoing pain in peripheral neuropathy.
AB  - OBJECTIVES: The aim of this study was to examine whether the intensity of dynamic
      mechanical allodynia and spontaneous ongoing pain in patients with neuropathic
      pain associated with peripheral neuropathy was influenced by an intravenous
      infusion of the 5HT3-antagonist, ondansetron. METHODS: A randomized, double
      blind, and placebo-controlled single intravenous infusion of 8 mg ondansetron or
      saline was administered to 15 patients during 10 minutes on 2 different occasions
      with an interval of at least 3 days. To monitor the brush-evoked allodynic
      percept over time, a computerized visual analog scale (VAS) was used allowing the
      patient to continuously rate the intensity and duration of pain. The area under
      the VAS curve was used to calculate the total brush-evoked pain intensity.
      Ongoing pain was rated using a VAS before each assessment of dynamic mechanical
      allodynia, that is, before and immediately after the infusion and at every 15
      minutes over a period of 3 hours. RESULTS: There was no influence of the factors
      with or without pain medication and treatment sequence (ie, ondansetron/saline or
      saline/ondansetron) on brush-evoked or ongoing pain intensity. No significant
      change over time was found after the infusion of either ondansetron or saline in
      the total brush-evoked pain intensity, in duration and frequency of
      aftersensation or in ongoing pain intensity. CONCLUSIONS: No influence from 8 mg
      of ondansetron could be shown on the intensity of brush-evoked or spontaneous
      ongoing pain in patients with peripheral neuropathy, indicating the lack of
      involvement of 5HT3-receptors in an earlier proposed spinobulbospinal loop with
      descending facilitation acting on spinal mechanisms related to dynamic mechanical
      allodynia.

PMID- 21178596
TI  - Association between intensity of pain and impairment in onset and activation of
      the deep cervical flexors in patients with persistent neck pain.
AB  - OBJECTIVES: This study evaluates the relationship between clinical symptoms and
      the function of the deep cervical flexor muscles in women with persistent neck
      pain. METHODS: Thirty-two women with a history of neck pain more than 6 months
      participated in the study. Measures for neck pain area, intensity, duration, and
      perceived disability were taken. Electromyography was acquired from the deep
      cervical flexor muscles by a nasopharyngeal electrode suctioned over the
      posterior oropharyngeal wall as the patients performed 2 tasks: rapid arm
      movements (shoulder flexion and extension) and isometric craniocervical flexion
      contractions. RESULTS: The patients' average score for the Neck Disability Index
      (0 to 50) was 11.0+/-2.6 and their average pain intensity rated on a visual
      analog scale (0 to 10) was 4.7+/-1.8. A correlation was observed between the
      average intensity of pain rated on the visual analog scale and the normalized
      electromyography amplitude recorded from the deep cervical flexors during the
      craniocervical flexion contractions (r=-0.36; P<0.05). Furthermore, the relative
      onset of the deep cervical flexors during rapid shoulder flexion was positively
      correlated with the average intensity of pain (r=0.50; P<0.01). No significant
      correlations were identified between the amplitude and the onset of activation of
      the deep cervical flexors and the duration of pain, area of pain, or Neck
      Disability Index score of the patient. DISCUSSION: This study shows a
      relationship between the levels of neck pain intensity and the function of the
      deep cervical flexor muscles in women with persistent neck pain but not in other
      clinical features, such as location or duration of the disorder. These findings
      may partially explain the heterogeneity in motor control impairments in patients
      with neck pain.

PMID- 21178595
TI  - Cross-validation of the Depression, Anxiety, and Positive Outlook Scale (DAPOS)
      for clinical use.
AB  - OBJECTIVE: The main objective of this study was to investigate different
      psychometric properties of the Swedish version of the Depression, Anxiety, and
      Positive Outlook Scale (DAPOS) in patients with chronic musculoskeletal pain in
      an orthopedic setting. METHODS: A total of 449 participants took part in the
      study, including 288 patients with chronic musculoskeletal pain and 161
      participants in a reference group. Internal consistency, convergent validity, and
      measurement invariance of the constructs of DAPOS were investigated across sex
      and diagnostic groups. The Beck Depression Inventory and the Spielberger Anxiety
      Inventory were used for measures of convergent validity. Multigroup confirmatory
      factor analysis was performed to test measurement invariance of the theoretical
      constructs of DAPOS. RESULTS: Internal consistency was good for all 3 constructs,
      and correlations concerned with convergent validity were found to be acceptable
      to good. With regard to cross-validation, the 3 constructs of DAPOS were strictly
      measurement invariant with respect to sex. Across diagnostic groups, the
      constructs of anxiety and positive outlook were almost strictly measurement
      invariant, although there were some restrictions of measurement invariance for
      the construct of depression. DISCUSSION: To be able to rely on an instrument with
      as few items as DAPOS, the cross-validation of its constructs for sex and
      diagnostic groups is a valuable information, particularly when investigated in
      patients with musculoskeletal pain. Based on these results, we recommend that
      DAPOS could replace longer and more time-consuming screening tests in clinical
      settings.

PMID- 21178597
TI  - Beliefs about back pain: results of a population survey of working age adults.
AB  - BACKGROUND: Beliefs about low back pain (LBP) have been widely studied. Research
      supports the importance of attitudes and beliefs in the development of
      disability. However, public opinions about LBP have been the subject of few
      studies to date and more research into public attitudes has been advocated to
      inform future public health initiatives. OBJECTIVES: To investigate public
      attitudes and beliefs about LBP, and the association of these with demographic
      variables. In addition, to determine whether certain group differences in
      demographic characteristics were useful in predicting individuals with negative
      attitudes about LBP. METHODS: A stratified sample of 3400 households were invited
      to participate in the Jersey Annual Social Survey. One thousand five hundred and
      seventy-four (46.3%) responded and 1132 (71.9%) were identified as being of
      working age. Complete responses to the Back Beliefs Questionnaire were provided
      by 1023 (65.0%). RESULTS: Respondents were grouped according to pain report: no
      current pain, current pain not LBP, and current LBP. Significant differences
      existed between subgroups for most demographic characteristics. Moreover, beliefs
      about LBP differed significantly between the 3 groups [F (2,1019)=17.72,
      P<0.001]. Further analyses were carried out for the subgroups separately. For the
      Current LBP group, beliefs differed significantly by educational level
      [F(2,186)=14.65, P<0.001], perceived general health [F (2,187)=4.42, P<0.05],
      acceptability of work absence [F (2,189)=10.69, P<0.001], LBP impact on activity
      [F (2,186)=6.38, P<0.01], and previous LBP absence [t (185)=4.84, P<0.001].
      Multiple regression using these characteristics produced an adjusted R of 0.25 [F
      (4,181)=16.33, P<0.001] for the prediction of back beliefs. DISCUSSION:
      Implications for public health initiatives and future research are discussed.

PMID- 21178598
TI  - Effect of intravenous lidocaine associated with amitriptyline on pain relief and
      plasma serotonin, norepinephrine, and dopamine concentrations in fibromyalgia.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of intravenous
      lidocaine combined with amitriptyline on pain relief and plasma serotonin,
      norepinephrine, and dopamine levels. METHODS: A prospective, randomized, double
      blind comparative study was conducted in 30 patients. All patients received 25 mg
      amitriptyline; monotherapy group (n=15) received 125 mL saline, and combined
      therapy group (n=15) received 240 mg lidocaine in 125 mL saline once a week for 4
      weeks. Serotonin, norepinephrine, and dopamine were measured in plasma at time
      zero (T0) and after 4 weeks (T4). Pain intensity was rated on a numerical scale
      at the beginning of the study and weekly for 4 weeks. RESULTS: All patients were
      females and the mean age was 44.7+/-10.5 years for monotherapy group and 40.9+/
      11.6 years for combined therapy group. No difference in pain intensity at
      baseline was observed between groups, with a decrease after treatment in
      monotherapy group (T0: 7.0+/-1.2 and T4: 4.0+/-2.1) and in combined therapy group
      (T0: 7.6+/-0.8 and T4: 4.1+/-2.3). Plasma serotonin and norepinephrine levels
      were similar in the 2 groups at T0 and T4. An increase in dopamine levels was
      observed in monotherapy group from the beginning to the end of treatment.
      CONCLUSIONS: Combined administration of 240 mg intravenous lidocaine (once a
      week) and 25 mg amitriptyline for 4 weeks did not modify pain intensity or plasma
      serotonin, norepinephrine, or dopamine concentrations in fibromyalgia patients.

PMID- 21178599
TI  - Effect of hypnosis on pain and blink reflexes in patients with painful
      temporomandibular disorders.
AB  - OBJECTIVE: This study contrasted the effect of hypnosis on self-reported pain and
      changes in a nociceptive brainstem reflex, the blink reflex (BR), in 39 women
      with temporomandibular disorder. METHODS: The patients were randomized to
      hypnosis or control (nonhypnotic relaxation). Pain intensity was assessed 3 times
      daily on a 0 to 10 numerical rating scale. BRs were elicited by electrical
      stimulation with a nociceptive-specific electrode and recorded before and after
      treatment at pain threshold (Ip) and supra threshold (2*Ip). RESULTS: Significant
      reduction of pain intensity was observed in the hypnosis group from 4.5+/-2.1 at
      baseline to 2.9+/-2.4 after treatment (P<0.001). The pain reduction was generally
      unrelated to changes in the BR, with the exception being a lowered ipsilateral R2
      BR component at the right side supra threshold (P=0.034). CONCLUSIONS: Hypnosis
      thus seems to reduce complex temporomandibular disorder pain, most likely because
      of cortical changes with little, if any, involvement of brainstem reflex
      pathways.

PMID- 21178600
TI  - Intermediate and long-term effects of a standardized back school for inpatient
      orthopedic rehabilitation on illness knowledge and self-management behaviors: a
      randomized controlled trial.
AB  - OBJECTIVES: A back school is a mandatory part of the multimodal rehabilitation
      program for patients with chronic low back pain in Germany. However, no
      standardized and evaluated back school program has been available for routine
      use. In this study, we report the evaluation of a new back school that was
      developed based on theories of health behavior, treatment evidence, practice
      guidelines, and quality criteria for patient education. METHODS: Randomized
      controlled trial of patients with low back pain (n=360) in inpatient orthopedic
      rehabilitation clinic in Germany. Intervention patients received the new back
      school, whereas control patients a traditional back school (usual care). Illness
      knowledge (primary outcome) and secondary behavioral and health outcomes were
      assessed at admission, discharge, and 6 and 12 months follow-up. RESULTS: Results
      showed a significant medium between-group treatment effect in patients' knowledge
      about back pain at discharge (eta2=0.081), after 6 (eta2=0.056), and 12 months
      (eta2=0.026). Furthermore, small-to-medium effects were observed among the
      secondary self-management behaviors, such as physical activity, back exercises,
      back posture habits, and coping with pain, after 6 and 12 months. DISCUSSION: The
      superior effectiveness of the back school based on a biopsychosocial approach was
      demonstrated with regard to illness knowledge and self-management behaviors up to
      1 year. Thus, the program may be recommended for dissemination within medical
      rehabilitation.

PMID- 21178601
TI  - Economic costs of nonmedical use of prescription opioids.
AB  - OBJECTIVES: Although the economic costs of substance misuse have been extensively
      examined in the published literature, information on the costs of nonmedical use
      of prescription opioids is much more limited, despite being a significant and
      rapidly growing problem in the United States. METHODS: We estimated the current
      economic burden of nonmedical use of prescription opioids in the United States in
      terms of direct substance abuse treatment, medical complications, productivity
      loss, and criminal justice. We distributed our broad cost estimates among the
      various drugs of misuse, including prescription opioids, down to the individual
      drug level. RESULTS: In 2006, the estimated total cost in the United States of
      nonmedical use of prescription opioids was $53.4 billion, of which $42 billion
      (79%) was attributable to lost productivity, $8.2 billion (15%) to criminal
      justice costs, $2.2 billion (4%) to drug abuse treatment, and $944 million to
      medical complications (2%). Five drugs--OxyContin, oxycodone, hydrocodone,
      propoxyphene, and methadone--accounted for two-thirds of the total economic
      burden. DISCUSSION: The economic cost of nonmedical use of prescription opioids
      in the United States totals more than $50 billion annually; lost productivity and
      crime account for the vast majority (94%) of these costs.

PMID- 21178602
TI  - Pain in Canadian NICUs: have we improved over the past 12 years?
AB  - OBJECTIVES: To determine the incidence of and factors predicting management
      strategies used for procedural pain in Canadian neonatal intensive care units and
      to determine whether the incidence of procedures and their management has changed
      since our 1997 study. PATIENTS: Five hundred eighty-two neonates who were
      hospitalized in any of the participating study centers were included. METHODS: A
      prospective observational study was conducted in 14 Canadian neonatal intensive
      care units (level III A and III B). Infants were followed for 1 week regarding
      all invasive procedures. Data were collected prospectively by unit staff using a
      checklist and verified by research assistants. RESULTS: A total of 3508 tissue
      damaging (mean=5.8, SD=15) and 14,085 (mean=25.6, SD=15) nontissue damaging
      procedures were recorded. Half of procedures (46% tissue damaging and 57%
      nontissue damaging) had no analgesic interventions. Opiates were used for 14.5%
      of tissue-damaging procedures and sweet taste was used for 14.3% of the tissue
      damaging procedures. Factors predicting use of pharmacologic management of tissue
      damaging procedures were being less ill at birth, receiving high frequency
      ventilatory support, and being transferred to the study center. Parental presence
      predicted use of sweet taste or nonpharmacologic analgesia for tissue-damaging
      procedures. Study site practices varied widely with 1 unit providing analgesia
      for 90% of tissue-damaging procedures. INTERPRETATION: Although the number of
      tissue-damaging procedures has decreased from 1997 and the use of analgesics has
      increased, the management of these procedures falls far below the recommended
      guidelines of the Canadian Pediatric Society. That 1 unit reached a high level of
      analgesic use suggests that it is possible to achieve this goal. That parental
      presence had a positive influence on comfort strategies supports offering
      encouragement and support for parents to remain with their infant during
      procedures.

PMID- 21178603
TI  - Pregabalin for peripheral neuropathic pain: a multicenter, enriched enrollment
      randomized withdrawal placebo-controlled trial.
AB  - OBJECTIVES: To date, published neuropathic pain randomized controlled trials of
      pregabalin have involved primarily diabetic peripheral neuropathy (DPN) and
      postherpetic neuralgia (PHN). This multicenter trial evaluated pregabalin in a
      broader range of neuropathic pain etiologies. METHODS: In this enriched
      enrollment randomized withdrawal trial, 256 patients received single blind,
      flexible dose pregabalin for 4 weeks; stable concomitant analgesics were allowed.
      One hundred sixty-five (65%) had a >=30% pain improvement and 157 were randomized
      and treated, double blind, to either continue pregabalin (n=80) or to receive
      placebo (n=77) for 5 weeks. RESULTS: Of the single blind responders randomized,
      81% on placebo and 86% on pregabalin completed the double-blind phase. At the
      double-blind endpoint, mean (SD) pain scores were 2.9 (1.9) in the pregabalin
      group and 3.5 (1.7) in the placebo group (P=0.002). These modest yet significant
      pregabalin-placebo differences were observed within each of the subgroups of
      patients with a diagnosis of either DPN or PHN (P=0.03), and with other diagnoses
      (P=0.02). Significant differences were also observed in sleep interference,
      Hospital Anxiety and Depression Scale Anxiety and Depression subscales, and other
      secondary measures. In total, 28 out of 80 (35.0%) in the pregabalin group and 28
      out of 77 (36.4%) in the placebo group had either a meaningful increase in pain
      or discontinued the double-blind phase. Adverse events were consistent with the
      known tolerability profile of pregabalin and led to discontinuation of 9 during
      the single-blind phase, and 5 and 2 patients from the placebo and pregabalin
      groups, respectively. DISCUSSION: These results support previous evidence of
      pregabalin efficacy but further demonstrate efficacy and tolerability in a
      broader range of peripheral neuropathic pain conditions beyond just DPN and PHN.

PMID- 21178604
TI  - The contribution of social capital and coping strategies to functioning and
      quality of life of patients with fibromyalgia.
AB  - OBJECTIVES: The study aimed to determine the degree to which social capital (a
      combination of social resources that can be beneficial to a person's physical
      health and well-being), personal coping strategies, and additional personal and
      disease-related factors, contribute to the functioning and quality of life (QoL)
      of fibromyalgia (FM) patients. METHODS: In the assessment of their functioning
      and QoL, 175 Israeli FM patients completed the Fibromyalgia Impact Questionnaire
      (FIQ) and the Short-Form Health Survey (SF-36) (dependent variables). In
      addition, they completed a modified Social Capital Questionnaires (which tests 3
      subtypes of social capital: bonding, bridging, and linking), COPE
      Multidimensional Coping Inventory (measures the use of problem vs. emotional
      focused coping strategies), and a personal demographic questionnaire (independent
      variables). A multivariate regression analysis was used to assess the relative
      contribution of each independent variable to functioning and QoL of these
      patients. RESULTS: The regression analysis showed that: (1) Bonding social
      capital and particularly the friend-connections component of bonding social
      capital contributed to the FIQ score and to the SF-36 parameters of social
      function, mental health, and bodily pain. (2) Problem-focused coping strategy
      contributed to the mental health parameter of the SF-36, whereas emotional
      focused coping strategy contributed negatively to the FIQ score and to the mental
      health, general health, and bodily pain parameters of the SF-36. (3) In addition,
      duration of FM symptoms contributed to the SF-36 parameters of general health,
      social function, mental health, and bodily pain but not to the FIQ score;
      whereas, work status contributed significantly to the variance of FIQ.
      DISCUSSION: Bonding social capital, problem-solving coping strategies, and the
      duration of FM contribute positively to functioning and QoL of FM patients;
      whereas, emotional-focused coping strategies do the opposite. Further research to
      test the effects of strengthened social capital and enhanced problem-solving
      rather than emotion-focused coping strategies on functioning and QoL of FM
      patients is warranted.

PMID- 21178605
TI  - Preemptive low-dose epidural ketamine for preventing chronic postthoracotomy
      pain: a prospective, double-blinded, randomized, clinical trial.
AB  - OBJECTIVES: Chronic postthoracotomy pain is the most common long-term
      complication that occurs after a thoracotomy with a reported incidence of up to
      80%. Although thoracic epidural analgesia is a widely used method for managing
      acute postthoracotomy pain, its effects seems questionable. The objective of this
      prospective, double-blinded, randomized, controlled trial was to assess the
      effect of preemptive low-dose epidural ketamine in addition to preemptive
      thoracic epidural analgesia on the incidence of chronic postthoracotomy pain.
      METHODS: We analyzed 133 patients who were randomized to preemptive thoracic
      epidural analgesia either with or without ketamine (Group K: 0.12%
      levobupivacaine, 2 MUg/mL of fentanyl, 0.2 mg/mL ketamine, total volume of 500 mL
      vs. Group KF: 0.12% levobupivacaine, 2 MUg/mL of fentanyl, total volume of 500
      mL). Pain at the thoracotomy scar site during rest and movement (coughing) was
      assessed at 2 weeks and 3 months after surgery using a visual analog scale. The
      incidence of allodynia and numbness was also evaluated. RESULTS: There was no
      difference in the incidence of chronic postthoracotomy pain at 3 months between
      the 2 groups (67.7% in group K vs. 75% in group KF). The incidences of allodynia
      or numbness were not different between the 2 groups. DISCUSSION: The addition of
      preemptive low-dose epidural ketamine (1.2 mg/h) to preemptive thoracic epidural
      analgesia did not have any beneficial effects in preventing chronic
      postthoracotomy pain.

PMID- 21178606
TI  - Fluoroscopic stellate ganglion block for postmastectomy pain: a comparison of the
      classic anterior approach and the oblique approach.
AB  - OBJECTIVE: Stellate ganglion block is usually performed with the classic anterior
      paratracheal approach. The anatomy of the stellate ganglion being in close
      proximity to various critical structures renders a number of complications, which
      are potentially associated with its blockade. The aim of this study was to assess
      the analgesic efficacy and safety of a new approach of the stellate ganglion
      block using an oblique fluoroscopic view. METHODS: Fifty patients with
      postmastectomy pain syndrome were randomly allocated into 1 of 2 groups: the
      anterior paratracheal stellate block group and the oblique fluoroscopic stellate
      block group. Four blocks were performed for each patient using the same approach
      each time. The results were evaluated in terms of pain intensity as assessed by
      the visual analog scale score, morphine consumption, and allodynia surface area
      (in cm). Patient satisfaction score (PSS), skin temperature, side effects, and
      complications were recorded and compared between the 2 studied groups after each
      block had been performed. RESULTS: The mean visual analog scale score, daily
      morphine consumption, and areas of allodynia were significantly decreased and the
      PSS was significantly increased after each block and for up to 3 months after the
      last block in both the groups. However, there were no statistically significant
      differences between the 2 groups at the same study period apart from PSS, which
      was statistically more significant in group oblique at certain times. The
      incidences of side effects were significantly more in group classic than in group
      oblique. CONCLUSIONS: The oblique fluoroscopic approach of the stellate ganglion
      block is as effective as the anterior paratracheal approach but is safer and more
      satisfactory to the patients.

PMID- 21178608
TI  - Nonalcoholic fatty liver disease in children.
AB  - PURPOSE OF REVIEW: Nonalcoholic fatty liver disease (NAFLD) has become the most
      common cause of liver disease in children from the developed world. The purpose
      of this review is to provide both a focused overview of pediatric NAFLD as well
      as a summary of the most recent advancements in the field. RECENT FINDINGS:
      Pediatric NAFLD is an underdiagnosed condition which can result in significant
      liver injury including cirrhosis. Although liver biopsy remains the standard for
      diagnosis and monitoring disease activity, several noninvasive biomarkers and
      imaging techniques hold significant promise. Dietary constituents, the intestinal
      bacterial flora, and sex hormones have been implicated as modulators of disease
      activity. NAFLD predisposition runs strongly in families and an allele in the
      PNPLA3 gene has shown a strong association with liver steatosis and hepatic
      inflammation. Treatment for pediatric NAFLD remains diet and exercise, but
      vitamin E may be a helpful adjunct. SUMMARY: Pediatric NAFLD shares many features
      with its adult counterpart but is a distinct entity which requires independent
      investigation. Our understanding of NAFLD in terms of epidemiology and risk
      factors has improved considerably but significantly more investigation is
      required to unravel its pathophysiology and identify novel therapeutic targets.

PMID- 21178607
TI  - Docosahexaenoic acid: brain accretion and roles in neuroprotection after brain
      hypoxia and ischemia.
AB  - PURPOSE OF REVIEW: With important effects on neuronal lipid composition,
      neurochemical signaling and cerebrovascular pathobiology, docosahexaenoic acid
      (DHA), a n-3 polyunsaturated fatty acid, may emerge as a neuroprotective agent
      against cerebrovascular disease. This paper examines pathways for DHA accretion
      in brain and evidence for possible roles of DHA in prophylactic and therapeutic
      approaches for cerebrovascular disease. RECENT FINDINGS: DHA is a major n-3 fatty
      acid in the mammalian central nervous system and enhances synaptic activities in
      neuronal cells. DHA can be obtained through diet or to a limited extent via
      conversion from its precursor, alpha-linolenic acid (alpha-LNA). DHA attenuates
      brain necrosis after hypoxic ischemic injury, principally by modulating membrane
      biophysical properties and maintaining integrity in functions between presynaptic
      and postsynaptic areas, resulting in better stabilizing intracellular ion balance
      in hypoxic-ischemic insult. Additionally, DHA alleviates brain apoptosis, by
      inducing antiapoptotic activities such as decreasing responses to reactive oxygen
      species, upregulating antiapoptotic protein expression, downregulating apoptotic
      protein expression, and maintaining mitochondrial integrity and function.
      SUMMARY: DHA in brain relates to a number of efficient delivery and accretion
      pathways. In animal models DHA renders neuroprotection after hypoxic-ischemic
      injury by regulating multiple molecular pathways and gene expression.

PMID- 21178609
TI  - Adaptive alterations in metabolism: practical consequences on energy requirements
      in the severely ill patient.
AB  - PURPOSE OF REVIEW: A recent and large multicentre study reports that ICU patients
      receive less than half of the recommended energy requirement. This review aims at
      clarifying whether underfeeding is scientifically justified or sustained by
      evidence-based medicine. RECENT FINDINGS: There is evidence that optimal
      nutrition improves clinical outcome of critically ill patients. The deleterious
      effect of overfeeding ICU patients is now well acknowledged, but underfeeding is
      not scientifically justified in ICU patients. Total energy expenditure in ICU
      patients is variable and methods to predict resting energy expenditure are
      questionable in these patients. SUMMARY: There is a need to measure energy
      expenditure in clinical practice. When not possible, the current guidelines on
      artificial nutrition (i.e. 25 kcal/kg per day) should be applied in order to
      limit underfeeding.

PMID- 21178610
TI  - Fatty acid regulation of hepatic lipid metabolism.
AB  - PURPOSE OF REVIEW: To discuss transcriptional mechanisms regulating hepatic lipid
      metabolism. RECENT FINDINGS: Humans who are obese or have diabetes (NIDDM) or
      metabolic syndrome (MetS) have low blood and tissue levels of C20-22
      polyunsaturated fatty acids (PUFAs). Although the impact of low C20-22 PUFAs on
      disease progression in humans is not fully understood, studies with mice have
      provided clues suggesting that impaired PUFA metabolism may contribute to the
      severity of risk factors associated with NIDDM and MetS. High fat diets promote
      hyperglycemia, insulin resistance and fatty liver in C57BL/6J mice, an effect
      that correlates with suppressed expression of enzymes involved in PUFA synthesis
      and decreased hepatic C20-22 PUFA content. A/J mice, in contrast, are resistant
      to diet-induced obesity and diabetes; these mice have elevated expression of
      hepatic enzymes involved in PUFA synthesis and C20-22 PUFA content. Moreover,
      loss-of-function and gain-of-function studies have identified fatty acid elongase
      (Elovl5), a key enzyme involved in PUFA synthesis, as a regulator of hepatic
      lipid and carbohydrate metabolism. Elovl5 activity regulates hepatic C20-22 PUFA
      content, signaling pathways (Akt and PP2A) and transcription factors (SREBP-1,
      PPARalpha, FoxO1 and PGC1alpha) that control fatty acid synthesis and
      gluconeogenesis. SUMMARY: These studies may help define novel strategies to
      control fatty liver and hyperglycemia associated with NIDDM and MetS.

PMID- 21178612
TI  - Treatment strategies for refractory status epilepticus.
AB  - PURPOSE OF REVIEW: Status epilepticus is one of the most common emergencies in
      neurology, and every third patient does not respond to adequate first-line
      treatment. Refractory status epilepticus may be associated with increased
      morbidity and mortality, and new treatment options are urgently required. This
      review critically discusses recently published data regarding the role of 'new'
      antiepileptic drugs, the efficacy and safety of anesthetic agents, and the
      overall clinical outcome that is an integral part of treatment decisions. RECENT
      FINDINGS: In complex partial status epilepticus, levetiracetam may be
      administered after failure of first-line and/or second-line agents. Lacosamide
      may be an interesting new adjunct, but reliable data are pending. In the
      treatment of refractory generalized convulsive status epilepticus, propofol seems
      to be as efficient as barbiturates. The latter are associated with prolonged
      ventilation times due to redistribution kinetics, whereas the former bears the
      risk of propofol infusion syndrome if administered continuously. Even after
      prolonged treatment with anesthetics over weeks, survival with satisfactory
      functional outcome is possible. SUMMARY: Unambiguous recommendations regarding
      treatment strategies for refractory status epilepticus are limited by a lack of
      reliable data. Therefore, randomized controlled trials or at least prospective
      observational studies based on strict protocols incorporating long-term outcome
      data are urgently required.

PMID- 21178611
TI  - Orally fed patients are at high risk of calorie and protein deficit in the ICU.
AB  - PURPOSE OF REVIEW: Malnutrition can lead to serious complications in the ICU.
      Less than half of patients admitted to ICU require ventilation and for many,
      their optimal route of feeding is oral medical nutrition therapy, rather than
      enteral or parenteral nutrition. Inadequate oral intake is a prevalent and often
      difficult problem within this population, as increased calorie deficits are
      common in the ICU and associated with worse outcomes. RECENT FINDINGS: Consuming
      less than 75% of daily calorie requirements in the hospital setting is associated
      with worse outcomes. Unfortunately, oral intake is often inadequate. Little is
      known about the consequences of inadequate oral intake in the ICU; however, data
      have described worse outcomes with large calorie deficits from enteral and
      parenteral nutrition. Whether or not these data can be extrapolated to patients
      in the ICU with poor oral intake remains uncertain. SUMMARY: Despite evidence
      based guidelines directing the delivery of nutrition support in the ICU, there is
      limited research focused on oral intake during this time of hospitalization.
      Future research is needed to determine the long-term associations of inadequate
      versus adequate oral intake in the ICU.

PMID- 21178613
TI  - Critical care of poor-grade subarachnoid hemorrhage.
AB  - PURPOSE OF REVIEW: Early aggressive treatment of poor-grade subarachnoid
      hemorrhage patients has resulted in more favorable long-term outcomes. This
      article covers the aspects of neurocritical care management directed to the
      patient with poor-grade subarachnoid hemorrhage (Hunt and Hess 4 and 5) and
      outlines important prognostic features. RECENT FINDINGS: Immediate
      cardiopulmonary and neurological support, early aneurysm repair, neuromodality
      and multimodality monitoring under the care of neurointensivists, treatment of
      medical complications, prevention and appropriate management of delayed cerebral
      ischemia have improved long-term outcomes after poor-grade subarachnoid
      hemorrhage. This includes control of intracranial hypertension, optimization of
      cerebral perfusion pressure and cardiac hemodynamics, correction of electrolyte
      abnormalities, and management of complications. Global cerebral edema, acute
      ischemic injury seen on diffusion-weighted imaging, and early vasospasm are
      disease states in the poor-grade patients that require attention and further
      investigation. Monitoring techniques such as surface and intracortical continuous
      electroencephalography, brain tissue oxygen monitoring, and microdialysis may
      detect secondary brain injury in a potentially reversible state. SUMMARY: Poor
      grade subarachnoid hemorrhage patients have the potential to recover and should
      therefore be fully resuscitated and treated aggressively with the available
      standards and monitoring techniques.

PMID- 21178614
TI  - Dialysis time: does it matter? A reappraisal of existing literature.
AB  - PURPOSE OF REVIEW: The length of time (Td) required for adequate maintenance
      hemodialysis therapy is perceived as a substantial patient burden. Technological
      advancements have allowed shortening Td over the past three decades. However,
      failure to detect improved outcomes with higher dialysis dose has prompted
      renewed interest in the potential impact of longer Td. RECENT FINDINGS: Ongoing
      trials are focused on increasing the frequency of treatments, although the
      feasibility of having most patients agreeing to more than five treatments per
      week remain doubtful. Furthermore, survival was better in short daily
      hemodialysis with Td of 180 vs. 90 min. Within thrice weekly dialysis, several
      recent epidemiological studies have shown improved survival associated with Td
      more than 4 h. Improved outcomes for long in-center nocturnal hemodialysis (6-8
      h, 3*/week), similar to what has been performed in Tassin for the last 30 years,
      have also been reported. SUMMARY: Compelling rationale and recent outcome data
      support use of longer Td. Improved management of salt and water may be the cause
      for the dissociation of dialysis time and small molecule clearance. In most
      industrialized countries, hemodialysis care systems in place have the capacity to
      accommodate it. Until such time that results from prospective randomized trials
      are available, we believe that physicians should prescribe and exert all efforts
      to convince thrice weekly hemodialysis patients to accept 4 h as minimum Td.

PMID- 21178616
TI  - Transplantation vs. conventional-dose therapy for amyloidosis.
AB  - PURPOSE OF REVIEW: Multiorgan involvement renders patients with AL amyloidosis
      particularly susceptible to treatment toxicity. The introduction of autologous
      stem cell transplantation (ASCT) represented a major advancement, but was
      associated with unacceptable toxicity in high-risk patients. Thus, efforts were
      made to improve the eligibility criteria for ASCT and to design novel, more
      effective, conventional-dose regimens. This review focuses on the role of ASCT
      and conventional-dose therapy in light of advances in risk stratification and
      patient monitoring. RECENT FINDINGS: The possibility of directly measuring the
      amyloidogenic precursor, the circulating free light chain (FLC), improved
      monitoring response to therapy. Cardiac biomarkers, N-terminal pro-natriuretic
      peptide type-B (NT-proBNP) and troponins (cTn) allow the most accurate prognostic
      stratification and direct the choice of therapy. Serial measurement of NT-proBNP,
      cTn and FLC are used to rapidly assess treatment efficacy. Bortezomib and immune
      modulatory drugs are going to play a major role in conventional-dose therapy and
      as adjuvant treatment after ASCT. SUMMARY: The choice between ASCT and
      conventional-dose chemotherapy is based on accurate risk assessment. Tight
      monitoring of hematologic and cardiac response is the cornerstone of treatment.
      Upcoming randomized trials will redefine the role of available therapies,
      assisting in the choice of the growing number of active regimens.

PMID- 21178615
TI  - Estrogen, hormonal replacement therapy and cardiovascular disease.
AB  - PURPOSE OF REVIEW: Premenopausal women have a lower risk and incidence of
      hypertension and cardiovascular disease (CVD) compared to age-matched men and
      this sex advantage for women gradually disappears after menopause, suggesting
      that sexual hormones play a cardioprotective role in women. However, randomized
      prospective primary or secondary prevention trials failed to confirm that hormone
      replacement therapy (HRT) affords cardioprotection. This review highlights the
      factors that may contribute to this divergent outcome and could reveal why young
      or premenopausal women are protected from CVD and yet postmenopausal women do not
      benefit from HRT. RECENT FINDINGS: In addition to the two classical estrogen
      receptors, ERalpha and ERbeta, a third, G-protein-coupled estrogen receptor
      GPR30, has been identified. New intracellular signaling pathways and actions for
      the cardiovascular protective properties of estrogen have been proposed. In
      addition, recent Women's Health Initiative (WHI) studies restricted to younger
      postmenopausal women showed that initiation of HRT closer to menopause reduced
      the risk of CVD. Moreover, dosage, duration, the type of estrogen and route of
      administration all merit consideration when determining the outcome of HRT.
      SUMMARY: HRT has become one of the most controversial topics related to women's
      health. Future studies are necessary if we are to understand the divergent
      published findings regarding HRT and develop new therapeutic strategies to
      improve the quality of life for women.

PMID- 21178617
TI  - Chemoradiation therapy in nonsmall cell lung cancer.
AB  - PURPOSE OF REVIEW: The majority of patients with nonsmall cell lung cancer
      (NSCLC) present with locally advanced mediastinal disease. Radiation therapy is
      the backbone, and nowadays a combination with chemotherapy is considered standard
      treatment. In this review we present a short history of the developments in this
      field with an update of all new developments. We address the questions how to
      optimally combine chemotherapy, targeted agents and radiation therapy. RECENT
      FINDINGS: The results from recently published papers dealing with combined
      chemoradiotherapy (CRT) and the data of two meta-analyses are reviewed. Some
      drugs are very suitable candidates for CRT such as cisplatin, pemetrexed and
      etoposide, whereas others should be avoided or used with caution (adriamycin,
      gemcitabine). SUMMARY: Our evaluation indicates that there are quite a number of
      positive developments in the treatment of locally advanced NSCLC but there is
      still much to improve. Variables such as patient condition, tumor biology, dose
      of radiation therapy, method of application (intensity modulated radiation
      therapy, four-dimensional planning) and dose of chemotherapy all influence
      treatment outcome and should be taken into account in designing the best
      treatment. Well-defined studies should be undertaken balancing the possible
      positive effect of therapy and toxicity.

PMID- 21178618
TI  - Graft dysfunction in pancreas and islet transplantation: morphological aspects.
AB  - PURPOSE OF REVIEW: beta-Cell replacement in the form of whole pancreas
      transplantation (WPnTx) or islet transplantation has the goal of providing long
      term insulin independence to diabetic patients that may require these types of
      interventions, with the minimum of iatrogenic side-effects and complications. In
      search of these ambitious and only partially achieved objectives, continuous
      advances are made in the field. RECENT FINDINGS: A concerted effort has been made
      in recent years to categorize the morphological features of allograft rejection
      in WPnTx. This has followed the general attempts to standardize histopathological
      and other diagnostic modalities in solid organ transplantation in general. Issues
      related to antibody-mediated rejection have taken center stage due to their
      perceived dramatic effects on both short and long-term graft survival. Another
      issue that diminishes the extent of success with WPnTx is the high incidence of
      posttransplant diabetes mellitus (PTDM). Understanding the mechanisms involved in
      this process is important for the development of potential therapeutic
      interventions and for its prevention. SUMMARY: This review will summarize the
      current understanding on the morphological features of antibody-mediated
      rejection in WPnTx, the main morphological and clinical aspects of PTDM,
      including recurrent autoimmune diabetes mellitus, and will briefly discuss
      histopathological data available on islet transplantation.

PMID- 21178619
TI  - Update on the management of parapharyngeal tumours.
AB  - PURPOSE OF REVIEW: Parapharyngeal space (PPSp) tumours are uncommon and hence the
      'generalist expertise' for diagnosis and treatment is limited. Recent
      improvements in radiology and cytopathology mean the likely diagnosis is more
      certain and hence the recommended surgical treatment can be more definitive.
      RECENT FINDINGS: A wide spectrum of primary pathologies are reported to involve
      the PPSp; the majority (80%) are benign neoplasms. Radiological imaging, computed
      tomography (CT) and MRI, with diagnostic fine needle aspiration cytology (FNAC),
      have continued to increase preoperative diagnostic accuracy. Thus, it is easier
      to identify the patients whose external surgery may rarely require a
      mandibulotomy. Only highly selected cases can be safely excised via a transoral
      approach. SUMMARY: All tumours of the PPSp require accurate diagnosis, using
      modern diagnostic imaging and FNAC. Surgery, in most cases, remains the treatment
      of choice. Many neurogenic tumours and paragangliomas can be observed in elderly
      patients. The optimum surgical approach for complete excision needs to be
      selected on an individual basis. Each patient must be adequately informed of the
      associated morbidity and possible complications, likelihood of cure and the risk
      of tumour recurrence - short and long term. Most tumours can be excised safely,
      and with low risk of recurrence and short hospitalization, with a cervical
      parotid approach.

PMID- 21178620
TI  - Isolated sphenoid sinus disease: differential diagnosis and management.
AB  - PURPOSE OF REVIEW: To review the current literature on isolated disease of
      sphenoid sinus, and to describe the various approaches to the sphenoid sinus.
      RECENT FINDINGS: Due to its posterior location and subtle presenting symptoms,
      sphenoid lesions, in the past, have often been missed and were reported as rare
      occurrences. However, with the availability of current diagnostic modalities such
      as endoscopy and imaging techniques such as computed tomography (CT) and magnetic
      resonance imaging (MRI), diseases of the sphenoid sinus are now more frequently
      diagnosed. Since the introduction of endoscopic techniques in the mid 1980s,
      various endoscopic approaches to the sphenoid sinus, depending on the extent and
      type of disease, have been described. These approaches were subsequently
      'extended' to remove pituitary tumours, and certain diseases of the parasellar
      region and the petrous apex. More recently, further extension of these approaches
      has led to the development of endoscopic skull base surgery, using the sphenoid
      sinus as the 'gateway' to the anterior, middle and the posterior cranial fossa.
      These approaches require a clear understanding of the anatomy of the sphenoid
      sinus and its surrounding regions. SUMMARY: This paper presents a review of the
      various diseases of the sphenoid sinus and describes the approaches to the sinus
      with special emphasis on the transpterygoid approach to the lateral recess of the
      sphenoid sinus.

PMID- 21178621
TI  - Pulsating airflow and drug delivery to paranasal sinuses.
AB  - PURPOSE OF REVIEW: There is a high incidence of nasal disorders, including
      chronic rhinosinusitis (CRS), affecting about 14% of the total population.
      Topical treatment regimens show only limited efficacy of drug delivery to the
      posterior nose and paranasal sinuses. Nevertheless, the primary treatment option
      of CRS is a combination of topical or systemic steroids, antibiotics and
      functional endonasal sinus surgery (FESS). RECENT FINDINGS: Sinus ventilation and
      paranasal aerosol deposition can be achieved by using pulsating airflow. Studies
      using pulsating airflow in nasal casts and in healthy volunteers have shown that
      up to 8% of the nasally deposited drug can deposit within the sinuses, which
      could not be achieved using nasal pump sprays. In addition, compared with nasal
      pump sprays, retention kinetics of the radiolabel deposit in the nose was
      prolonged. SUMMARY: With this efficiency, topical aerosol therapies of sinus
      disorders can be achieved and, due to the prolonged retention, reduced
      application modes are possible. This offers new treatment options of sinus-nasal
      disorders prior or after FESS.

PMID- 21178622
TI  - Use of prokinetics in the preterm infant.
AB  - PURPOSE OF REVIEW: Functional gastrointestinal dysmotility is a common condition
      that affects premature infants. Delay in achievement of full enteral nutrition
      results in dependence on prolonged parenteral nutrition, predisposing to adverse
      outcomes. Studies in recent years show apparently conflicting results regarding
      the use of prokinetic agents in preterm infants. This review aims to evaluate
      these studies to determine whether use of these agents in premature infants is
      beneficial and justified. RECENT FINDINGS: Randomized controlled trials in recent
      years have been performed to investigate the effectiveness of erythromycin in the
      treatment of nonobstructive gastrointestinal dysmotility in preterm infants.
      Overall, neither low-dose regimes nor prophylactic trials have been shown to be
      useful. High-dose regimes used as rescue therapy of infants with established
      gastrointestinal dysmotility have consistently shown clinical benefit.
      Theoretical risks of prolonged antibiotic use, such as emergence of antibiotic
      resistance and abnormal intestinal microbiota, have not been fully evaluated.
      SUMMARY: Judicious use of high-dose erythromycin in premature infants as rescue
      therapy is probably justifiable. Further research in this area is warranted to
      develop newer prokinetic agents which may improve the safety profile of therapy.

PMID- 21178623
TI  - Continuous renal replacement therapy: mechanism of clearance, fluid removal,
      indications and outcomes.
AB  - PURPOSE OF REVIEW: Continuous renal replacement therapy (CRRT) is the most common
      dialysis modality provided to critically ill children with acute kidney injury
      (AKI). However, confusion still exists with respect to CRRT terminology and the
      optimal use of this modality across the entire pediatric disease and age
      spectrum. RECENT FINDINGS: Data from both single-center and multicenter pediatric
      studies demonstrate that CRRT can be provided effectively to all pediatric
      patients, from infants to young adult aged patients. Furthermore, these data
      demonstrate a consistent and independent association between the degree of
      patient fluid accumulation at the initiation of a CRRT course and mortality in
      critically ill children with AKI. In addition, CRRT has been successfully
      utilized for rapid clearance of both exogenous and endogenous (e.g., ammonia)
      toxins without the concentration rebound that characterizes toxin removal by
      intermittent hemodialysis. SUMMARY: CRRT represents an essential dialytic
      modality for the pediatric nephrologist caring for critically ill children.
      Current data suggest that earlier initiation of CRRT to prevent excessive fluid
      accumulation may lead to improved survival in critically ill children, but
      prospective trials are required to test this hypothesis directly.

PMID- 21178624
TI  - Neuroimaging correlates of aggression in schizophrenia: an update.
AB  - PURPOSE OF REVIEW: Aggression in schizophrenia is associated with poor treatment
      outcomes, hospital admissions, and stigmatization of patients. As such it
      represents an important public health issue. This article reviews recent
      neuroimaging studies of aggression in schizophrenia, focusing on PET/single
      photon emission computed tomography and MRI methods. RECENT FINDINGS: The
      neuroimaging literature on aggression in schizophrenia is in a period of
      development. This is attributable in part to the heterogeneous nature and basis
      of that aggression. Radiological methods have consistently shown reduced activity
      in frontal and temporal regions. MRI brain volumetric studies have been less
      consistent, with some studies finding increased volumes of inferior frontal
      structures, and others finding reduced volumes in aggressive individuals with
      schizophrenia. Functional MRI studies have also had inconsistent results, with
      most finding reduced activity in inferior frontal and temporal regions, but some
      also finding increased activity in other regions. Some studies have made a
      distinction between types of aggression in schizophrenia in the context of
      antisocial traits, and this appears to be useful in understanding the
      neuroimaging literature. SUMMARY: Frontal and temporal abnormalities appear to be
      a consistent feature of aggression in schizophrenia, but their precise nature
      likely differs because of the heterogeneous nature of that behavior.

PMID- 21178625
TI  - Advances in chronic obstructive pulmonary disease among older adults.
AB  - PURPOSE OF REVIEW: This review summarizes recent research on chronic obstructive
      pulmonary disease (COPD) among older adults. RECENT FINDINGS: Recent research on
      COPD and older adults addresses four key areas: diagnosis and screening,
      comorbidities, end-of-life care, and management. These key findings include the
      Rotterdam study's identification of the incidence rate of COPD in older adults
      being 9.2 per 1000 person-years; a new assessment of FEV1 cut-points associated
      with increased prevalence of respiratory symptoms and risk of death; development
      and validation of new mortality scales, the ADO (age, dyspnea, and airflow
      obstruction) index and the PILE score; older adults with COPD average 9
      comorbidities, of which depression, cardiovascular diseases such as hypertension,
      and chronic renal failure are highly prevalent; nonrespiratory treatments such as
      proton pump inhibitors, angiotensin-converting enzyme inhibitors, and statins
      show promise in the management of COPD; and strength may be a protective factor
      for older adults with COPD. SUMMARY: Findings suggest that more research on older
      adults and COPD suggest that aging is a determinant of the progression of disease
      and that management of this population requires different metrics and strategies.

PMID- 21178626
TI  - Trends in chronic obstructive pulmonary disease in the Asia-Pacific regions.
AB  - PURPOSE OF REVIEW: The burden of chronic obstructive pulmonary disease (COPD) is
      rapidly growing in the Asia-Pacific region. There is the need for region-specific
      research and analysis of the epidemiology of COPD to raise awareness of the
      disease and highlight its causes. Such information is essential to for the
      development of effective national health policies to ensure evidence-based
      deployment of finite healthcare resources in the prevention and management of
      COPD. RECENT FINDINGS: Recent population-based epidemiological studies have
      confirmed previous assumptions that COPD in the Asia-Pacific region is as
      prevalent as in the mature economies of the western world. The greatest numbers
      of deaths and hospitalizations from COPD are concentrated in this populous region
      of the world. The patterns in trends in mortality and hospitalization in the past
      10 years in Asia-Pacific countries show a spectrum from the 'mature' to the
      'evolving' and are likely related to the combined effects of cigarette smoking
      and nonsmoking risk factors. Gross underdiagnosis of COPD and underutilization of
      spirometry further contribute to burden and are barriers to appropriate and
      timely management of COPD. SUMMARY: COPD is a common disease with a large disease
      burden throughout the Asia-Pacific region. Effective public health preventive
      measures coupled with timely case detection are needed for the reversal of trends
      and the reduction of disease burden.

PMID- 21178627
TI  - Emphysema and chronic obstructive pulmonary disease in coal miners.
AB  - PURPOSE OF REVIEW: Coal mining remains a major industry that has workers at risk
      for developing chronic lung disease. Aside from simple coal workers'
      pneumoconiosis and progressive massive fibrosis, the development of emphysema and
      obstructive lung disease independent of smoking may be underappreciated. This
      article reviews more recent studies that may help rectify this faulty view.
      RECENT FINDINGS: Cumulative exposure to coal dust is a significant risk factor
      for the development of emphysema and has an additive effect to smoking. Increased
      coal dust exposure is associated with increased risk of death from chronic
      obstructive pulmonary disease (COPD). In newly employed coal miners, bronchitic
      symptoms are associated with a rapid decline in lung function within 2 years
      after starting work. In evaluating impairment, the chest radiograph may be
      helpful as a marker of exposure but the diffusing capacity is most correlated
      with dyspnea, whereas the emphysema computed tomography score has good
      association with expiratory flow limitation. SUMMARY: Latest studies further
      support the association of emphysema and COPD with coal dust exposure. Increased
      cumulative exposure may also increase risk of death from these diseases.

PMID- 21178628
TI  - Immediate and short-term consequences of secondhand smoke exposure on the
      respiratory system.
AB  - PURPOSE OF REVIEW: This review critically evaluates the existing biological
      evidence regarding the immediate and short-term respiratory consequences of
      secondhand smoke (SHS). RECENT FINDINGS: A 1-h exposure to SHS at bar/restaurant
      levels generates a marked inflammatory reaction and significant decrements on
      lung function. These deleterious effects of SHS are exacerbated when physical
      activity follows the SHS exposure, particularly in less fit individuals. The main
      respiratory effect mechanisms of SHS include a direct induction of growth factors
      resulting in airway remodelling and alterations in nitric oxide regulation.
      Pharmacological agents that increase either apical membrane chloride conductance
      or basolateral membrane potassium conductance may be of therapeutic benefit in
      patients with diseases related to SHS exposure. Moreover, treatment with statins
      has shown beneficial effects towards preventing the SHS-induced pulmonary
      hypertension, vascular remodelling, and endothelial dysfunction. SUMMARY: Based
      on recently discovered evidence, even brief and short-term exposures to SHS
      generate significant adverse effects on the human respiratory system. Future
      research directions in this area include the concentrations of tobacco smoke
      constituents in the alveolar milieu following SHS exposure, individual
      susceptibility to SHS, as well as pharmacological treatments for reversing the
      SHS-induced airway remodelling.

PMID- 21178629
TI  - Exercise for bone health: rationale and prescription.
AB  - PURPOSE OF REVIEW: Patients frequently inquire about exercise as a means to
      improve bone strength and reduce osteoporotic fracture. Understanding the
      biologic mechanisms and the available clinical evidence supporting the role of
      exercise in bone health is the key to an educated discussion. RECENT FINDINGS:
      Exercise downregulates sclerostin expression by the osteocyte favoring
      osteoblastogenesis. These changes are enhanced by dynamic cyclical load with rest
      periods and may be promoted by low-amplitude high-frequency stimuli. In the
      prepubertal years, exercise results in periosteal gains, whereas exercise later
      in life maintains bone mass, reduces falls and probably associated fractures, and
      improves quality-of-life measures. SUMMARY: Future studies should examine the
      effect of exercise on bone strength and determine the minimum quantity and
      frequency and the exercise type most effective to reduce osteoporotic fractures.

PMID- 21178630
TI  - Uric acid in heart disease: a new C-reactive protein?
AB  - PURPOSE OF REVIEW: To review and interpret the recently published data on
      hyperuricemia and cardiovascular disease to present an opinion on the nature of
      link between serum uric acid concentration and the risk for cardiovascular
      outcomes, and to comment on its implications for clinical practice. RECENT
      FINDINGS: Evidence has accumulated in prospective observational studies that link
      hyperuricemia among younger adults with the risk of subsequent hypertension. Such
      associations have been observed with respect to insulin resistance, diabetes, and
      other cardiovascular risk factors. Newer data confirm the link between
      hyperuricemia and cardiovascular mortality. The use of allopurinol has been shown
      to be associated with reduced mortality risk in longer term observational studies
      and with reduced blood pressure in short-term randomized controlled trials. None
      of these findings is confounded by traditional risk factors. SUMMARY: The
      available evidence has established a link between hyperuricemia and
      cardiovascular disease and this may be causal. Without waiting for the resolution
      of causality arguments, one can start using serum uric acid concentration as an
      inexpensive cardiovascular risk marker.

PMID- 21178631
TI  - Innovations in prostate biopsy strategies for active surveillance and focal
      therapy.
AB  - PURPOSE OF REVIEW: Active surveillance and focal therapy for prostate cancer have
      been proposed as treatment alternatives for prostate cancer. In this review, we
      track the emerging technologies that will support the viability of such
      management strategies. RECENT FINDINGS: Widespread prostate-specific antigen
      (PSA) testing and extended prostate biopsy practice patterns have resulted in a
      significant increase in the diagnosis of low-risk prostate cancer. As most low
      risk prostate cancers may not require radical treatment, alternatives for
      appropriately selected patients have been proposed and implemented - namely,
      active surveillance and focal therapy. Both alternatives to radical therapy
      require accurate mapping and precise targeting of lesions within the prostate,
      for which current technological shortfalls limit their clinical utility. The
      emerging tools that will help overcome these challenges include refined imaging
      modalities, three-dimensional modeling for planning and tracking intervention,
      elastic fusion image technology, and automated mechanical delivery of the
      intervention needle. SUMMARY: Current prostate biopsy technologies have largely
      advanced as separate entities. Further refinement of these innovations continue,
      but the ultimate challenge will be integrating them into one comprehensive
      platform.

PMID- 21178632
TI  - Indications and outcomes of laparoscopic uretero-renal stone surgery.
AB  - PURPOSE OF REVIEW: Although most ureteral and urinary stones are managed using
      endourologic techniques or shockwave lithotripsy in daily clinical practice,
      stone surgery has not completely disappeared. Laparoscopy, another minimally
      invasive treatment, is continuously gaining place in the treatment of urinary
      stones, mainly replacing open surgery. RECENT FINDINGS: Indications for open or
      laparoscopic stone surgery are anatomic abnormalities, such as horseshoe kidneys,
      malrotated kidneys, ureteropelvic junction obstruction with stones, or ectopic
      kidneys; symptomatic stones in diverticula; extremely large stones and all those
      situations in which conventional endourologic procedures and extracorporeal shock
      wave lithotripsy are not available or were unsuccessful or in those conditions
      where laparoscopy offers a priori the best solution to an endourologic complex
      condition. SUMMARY: Laparoscopic surgery is effective for complex urinary stones
      and allows adjunctive procedures. It complements other minimally invasive
      procedures, and a need for open surgery has strongly diminished.

PMID- 21178634
TI  - Differential clinical characteristics, medication usage, and treatment response
      of bipolar disorder in the US versus The Netherlands and Germany.
AB  - Increased early-onset bipolar illness was seen in the US compared with the
      Netherlands and Germany (abbreviated here as Europe), but other clinical
      characteristics, medication use, and treatment response have not been
      systematically explored. Outpatients with bipolar disorder were treated
      naturalistically and followed prospectively at four sites in the US and three in
      Europe. Data and clinical characteristics were collected from patient
      questionnaires, and medication usage and good-to-excellent response to treatment
      for at least 6 months ascertained from daily clinician ratings on the National
      Institutes of Mental Health-Life Chart Method. Almost all clinical
      characteristics earlier associated with a poor treatment response were more
      prevalent in the US than in Europe, including early onset, environmental
      adversity, rapid cycling, more than 20 prior episodes, comorbid anxiety and
      substance abuse disorders, and a positive parental history for an affective
      disorder. Lithium was used more frequently in Europe than in the US and had a
      higher rate of success, whereas valproate was used more in the US, with a trend
      toward higher success in Europe. Antidepressants were used more in the US, but
      had extremely low success rates. Many other agents were deployed differently on
      the two continents, but success rates were consistently lower in the US than in
      Europe. In conclusion, clinical characteristics and patterns of medication usage
      and effectiveness differed markedly in the two continents suggesting the need for
      uncovering explanations and considering the two populations as heterogeneous in
      the future pharmacological studies.

PMID- 21178633
TI  - Identifying cochlear implant channels with poor electrode-neuron interfaces:
      electrically evoked auditory brain stem responses measured with the partial
      tripolar configuration.
AB  - OBJECTIVES: The goal of this study was to compare cochlear implant behavioral
      measures and electrically evoked auditory brain stem responses (EABRs) obtained
      with a spatially focused electrode configuration. It has been shown previously
      that channels with high thresholds, when measured with the tripolar
      configuration, exhibit relatively broad psychophysical tuning curves. The
      elevated threshold and degraded spatial/spectral selectivity of such channels are
      consistent with a poor electrode-neuron interface, defined as suboptimal
      electrode placement or reduced nerve survival. However, the psychophysical
      methods required to obtain these data are time intensive and may not be practical
      during a clinical mapping session, especially for young children. Here, we have
      extended the previous investigation to determine whether a physiological approach
      could provide a similar assessment of channel functionality. We hypothesized
      that, in accordance with the perceptual measures, higher EABR thresholds would
      correlate with steeper EABR amplitude growth functions, reflecting a degraded
      electrode-neuron interface. DESIGN: Data were collected from six cochlear implant
      listeners implanted with the HiRes 90k cochlear implant (Advanced Bionics).
      Single-channel thresholds and most comfortable listening levels were obtained for
      stimuli that varied in presumed electrical field size by using the partial
      tripolar configuration, for which a fraction of current (sigma) from a center
      active electrode returns through two neighboring electrodes and the remainder
      through a distant indifferent electrode. EABRs were obtained in each subject for
      the two channels having the highest and lowest tripolar (sigma = 1 or 0.9)
      behavioral threshold. Evoked potentials were measured with both the monopolar
      (sigma = 0) and a more focused partial tripolar (sigma >= 0.50) configuration.
      RESULTS: Consistent with previous studies, EABR thresholds were highly and
      positively correlated with behavioral thresholds obtained with both the monopolar
      and partial tripolar configurations. The Wave V amplitude growth functions with
      increasing stimulus level showed the predicted effect of shallower growth for the
      partial tripolar than for the monopolar configuration, but this was observed only
      for the low-threshold channels. In contrast, high-threshold channels showed the
      opposite effect; steeper growth functions were seen for the partial tripolar
      configuration. CONCLUSIONS: These results suggest that behavioral thresholds or
      EABRs measured with a restricted stimulus can be used to identify potentially
      impaired cochlear implant channels. Channels having high thresholds and steep
      growth functions would likely not activate the appropriate spatially restricted
      region of the cochlea, leading to suboptimal perception. As a clinical tool,
      quick identification of impaired channels could lead to patient-specific mapping
      strategies and result in improved speech and music perception.

PMID- 21178635
TI  - Grip force control is dependent on task constraints in children with and without
      developmental coordination disorder.
AB  - Excessive grip force (GF) is often found in children with developmental
      coordination disorder (DCD). However, their GF control may vary when task
      constraints are imposed upon their motor performance. This study aimed to
      investigate how their GF control changes in response to task demands, and to
      examine their tactile sensitivity. Twenty-one children with DCD and 17 controls
      participated in the study. The instrument used to measure GF was a cylindrical
      cup equipped with a load cell. The children were asked to hold and transport
      three cups with varying physical properties as quickly as possible. For tactile
      function, static and moving two-point discrimination senses were recorded. Data
      were analyzed using repeated-measures analysis of covariance. Children with DCD
      displayed slower rate of GF generation, which might be related to their lower
      sensitivity of two-point dynamic discrimination. Given the slow rate of GF
      generation and time constraint, the peak GF for children with DCD was lower than
      that for the control children, but the peak GF of both the groups depended on the
      time allowed for the performance and the task demand. Both the groups of children
      cautiously modulated the grip when the cup was filled with water, and graded GF
      according to the physical property of the cup. We conclude that GF control in
      children with or without DCD was task dependent.

PMID- 21178636
TI  - The new electroanatomical Carto3 mapping system: three-dimensional right
      ventricular fast anatomical map resolution in comparison to magnetic resonance
      image.
AB  - Three-dimensional mapping systems are required in some electrophysiological
      procedures in order to allow nonfluoroscopic catheter navigation, reconstruction
      of electrophysiological mechanisms, particularly of complex arrhythmias, and to
      facilitate catheter ablation. Accuracy in three-dimensional reconstructions of
      cardiac chambers is crucial to increase the effectiveness and safety of
      electrophysiological procedures. We report on the feasibility of the anatomical
      reconstruction of the right ventricular chamber by means of the new Carto3
      system. The three-dimensional anatomical reconstruction of the right ventricle
      was compared to the magnetic resonance image of the same chamber.

PMID- 21178637
TI  - High-dose cytosine arabinoside-induced symptomatic bradycardia.
AB  - Cardiac complications of high-dose cytosine arabinoside (HiDAC), although rare,
      predominantly include pericarditis, pericardial effusion and cardiomyopathy (with
      concurrent use of cyclophosphamide). Clinically significant arrhythmias
      associated with HiDAC, although reported in the literature, are rare. The
      following case report has for the first time used the Naranjo Scale to document a
      high-probability association (definite adverse drug reaction) of cytarabine with
      symptomatic sinus bradycardia. 

PMID- 21178638
TI  - B-type natriuretic peptide levels predict functional capacity in postcardiac
      surgery patients.
AB  - OBJECTIVE: Plasma levels of B-type natriuretic peptide (BNP) are often increased
      in postcardiac surgery patients. The six-minute walking test (6MWT) is useful to
      assess functional capacity in postcardiac surgery patients. The aim of this study
      was to determine whether BNP levels are associated with exercise capacity
      evaluated by 6MWT in patients after cardiac surgery. METHODS: Plasma BNP was
      measured in 101 consecutive patients referred to our center 8 +/- 5 days after
      cardiac surgery who underwent echocardiography and 6MWT. We considered age, sex,
      diabetes, renal insufficiency, anemia, chronic obstructive pulmonary disease,
      hypertension, atrial fibrillation, beta-blocker therapy, left ventricular
      ejection fraction (LVEF), E/E', indexed left atrial volume (iLAV), type of
      surgery, and plasma BNP levels as potential predictors of reduced performance at
      6MWT evaluated as percentages of the predicted values calculated according to the
      regression equation obtained in healthy individuals. RESULTS: The mean distance
      walked at 6MWT was 325 +/- 100 m corresponding to 65 +/- 20% of the predicted
      values. This was independent of the LVEF, E/E' or iLAV. Female patients or
      patients with atrial fibrillation had a reduced performance compared with male
      patients or patients with sinus rhythm (52 +/- 19 vs. 70 +/- 19%, P < 0.001; 50
      +/- 19 vs. 66 +/- 19%, P = 0.017, respectively). BNP levels were inversely
      related to the performance at 6MWT (Pearson's correlation coefficient = -0.25, P
      = 0.010). At multivariate analysis, female sex (P < 0.001), atrial fibrillation
      (P = 0.031), and BNP levels (P = 0.040) remained the only independent predictive
      factors for reduced exercise capacity. CONCLUSION: The increase in BNP levels in
      postcardiac surgery patients is associated with reduced exercise capacity.

PMID- 21178639
TI  - Surgical procedures in the DANTE trial, a randomized study of lung cancer early
      detection with spiral computed tomography: comparative analysis in the screening
      and control arm.
AB  - BACKGROUND: The patient population derived from lung cancer screening programs
      with low-dose spiral computed tomography (LDCT) is different from the general
      population accessing thoracic surgical services. METHODS: Retrospective review of
      all surgical cases in the DANTE trial, a randomized study of lung cancer
      screening with LDCT. Patient characteristics, workup, procedures, resections for
      benign disease, complications, tumor features, and final outcomes have been
      analyzed in the LDCT and in the control arm. RESULTS: In the LDCT arm, 77
      suspicious lesions were surgically managed in 72 patients. A benign lesion was
      diagnosed in 17 cases (22%). Major video-assisted thoracoscopic surgery resection
      was carried out in five lung cancer cases (7%) and segmentectomy in 11 (19%).
      Complete resection was achieved in 93%, and stage I rate was 73%. Two patients
      had a local recurrence after open lobectomy, and three had a resectable new
      primary. In the control group, 28 patients underwent 31 surgical procedures, in
      five cases (16%) for benign lesions. No major video-assisted thoracoscopic
      surgery resections were carried out. Resectability rate was 88%, and stage I rate
      was 52%. Five patients had a local recurrence and two had a second primary.
      CONCLUSIONS: Surgery for benign lesions is a relevant issue in screening-derived
      patients. Local control may be achieved by minimally invasive techniques or
      segmentectomy; however, developing the necessary skills requires an effort by the
      surgical team. Long-term survivors have a noticeable chance of developing second
      primary cancers or resectable recurrences and may benefit from a second
      resection.

PMID- 21178640
TI  - Potential role of platelet-derived growth factor receptor inhibition using
      imatinib in combination with docetaxel in the treatment of recurrent non-small
      cell lung cancer.
AB  - INTRODUCTION: Platelet-derived growth factor receptor (PDGFR) is expressed in
      lung cancer and is involved in angiogenesis. Preclinical models demonstrated that
      imatinib (Im) regulates angiogenesis through PDGFR inhibition and enhances
      efficacy of chemotherapy. HYPOTHESIS: We hypothesized that Im plus docetaxel (D)
      would have a synergistic effect detectable by an increase in response rate in
      patients with recurrent non-small cell lung cancer (NSCLC). METHODS: A phase II
      trial to evaluate Im in combination with D in patients with recurrent NSCLC was
      conducted. The primary end point was response rate, using a Simon two-stage
      design. Eligible patients had measurable disease and no more than two
      chemotherapy regimens. D was given at 30 mg/m/wk intravenously * 3 every 4 weeks
      and oral Im at 600 mg daily for four cycles. Patients required two cycles to be
      evaluable for response. Nonprogressors after four cycles continued with Im
      maintenance until progression or for a total of 12 months. RESULTS: Twenty-three
      patients were enrolled in the first stage. Toxicity was mainly nonhematologic. We
      observed one partial response (5.5%), four stable disease (22.2%), and 13
      progressed (72.2%). Median time to progression was 1.9 months, and median overall
      survival was 6.1 months. Two patients who went on Im maintenance had time to
      progression of 7.78 months and 15.8 months. CONCLUSION: Im in combination with D
      did not achieve its primary objective of improving response rate in patients with
      recurrent NSCLC. An increased understanding of the complex PDGFR pathway in lung
      cancer and alternative strategies to inhibit it are needed.

PMID- 21178641
TI  - Hormone therapy and recurrence of venous thromboembolism among postmenopausal
      women.
AB  - OBJECTIVES: The route of estrogen administration is an important determinant of
      the risk of the first venous thromboembolism (VTE) event in postmenopausal women
      using hormone therapy (HT). However, the impact of transdermal estrogens on VTE
      recurrence risk has not been investigated. The aim of our study was to assess the
      impact of HT by route of estrogen administration on the risk of recurrent VTE.
      METHODS: A total of 1,023 consecutive postmenopausal women aged 45 to 70 years
      with a confirmed first VTE were recruited from an outpatient clinic of a
      hemostasis hospital unit between January 2000 and December 2008 and were followed
      for an average of 79 months after discontinuation of anticoagulation therapy.
      RESULTS: Recurrent VTE occurred in 77 women (1.1% per year). During the follow
      up, 130 women used HT (12.7%), including 103 transdermal estrogen users (10.0%)
      and 10 oral estrogen users (1.0%). After adjustment for potential confounders,
      there was no significant association between recurrent VTE and use of transdermal
      estrogens (hazard ratio, 1.0; 95% CI, 0.4-2.4), with the nonusers as a reference
      group. In contrast, women using oral estrogens had an increased risk of recurrent
      VTE (hazard ratio, 6.4; 95% CI, 1.5-27.3). Consistently, no subgroup of women had
      evidence of a risk of recurrent VTE with transdermal HT that significantly
      differed from that observed for all women. CONCLUSIONS: Oral but not transdermal
      estrogens are associated with a higher risk of recurrent VTE among postmenopausal
      women. This result provides further epidemiological evidence that transdermal
      estrogens may be safe with respect to VTE risk.

PMID- 21178642
TI  - Cancer prevalence in osteoporotic women with low serum vitamin D levels.
AB  - OBJECTIVE: The aim of this study was to assess the role of vitamin D in cancer
      development in postmenopausal osteoporotic women. METHODS: A cross-sectional and
      in vitro study was carried out, with statistical analysis with odds ratios and
      95% CIs presented. Human estrogen receptor-positive breast cancer cells (MCF-7)
      were studied in vitro. The apoptosis-to-proliferation (A/P) ratio was also
      determined. RESULTS: A total of 885 women were included in this study. Any kind
      of cancer was found in 112 (12.7%) of all women. Breast cancer was the most
      prevalent malignancy, representing half of the cases (n = 56, 50%). The
      prevalence of any kind of cancer and breast cancer in women with low 25
      hydroxyvitamin D3 levels (25OHD; <50 nmol/L) was higher than in women with high
      25OHD levels (>= 50 nmol/L). The in vitro study demonstrated a statistically
      significant increased A/P ratio of 5.27 (95% CI, 4.054-6.493) with a high
      concentration of 1alpha,25-dihydroxyvitamin D (10 MUM) after 96 hours.
      CONCLUSIONS: Osteoporotic women with low serum levels of 25OHD (<50 nmol/L) have
      an increased prevalence of any kind of cancer and breast cancer; however, these
      differences are not statistically significant. 1alpha,25-dihydroxyvitamin D
      induced an increased A/P ratio in MCF-7 breast cancer cells in vitro.

PMID- 21178643
TI  - Emotional faces boost up steady-state visual responses for brain-computer
      interface.
AB  - Steady-state visual evoked potentials (SSVEPs) can be used successfully for brain
      computer interfaces (BCI) with multiple commands and high information transfer
      rates. In this study, we investigated a novel affective SSVEP paradigm using
      flickering video clips of emotional human faces, and evaluated their performance
      in an 8-command BCI controlling a robotic arm in near real-time. Single-trial
      affective SSVEP responses, estimated using a new phase-locking value variability
      and a wavelet energy variability measures, were significantly enhanced compared
      with blurred-face flicker and standard checkerboards. For multicommand SSVEP
      based BCI, affective face-flicker boosted up the information transfer rates from
      50 to 64 bits/min, while reducing user fatigue and enhancing visual attention and
      reliability. In the 5-12 Hz flicker frequency range, the strongest affective
      SSVEP responses were obtained at 10 Hz. These findings suggest new directions for
      SSVEP-based neural applications, including affective BCI and enhanced steady
      state clinical probes.

PMID- 21178644
TI  - Human auditory cortical responses to pitch and to pitch strength.
AB  - Pitch is a fundamental auditory sensation, underlying both music and speech
      perception. This study was designed to explore pitch coding in human auditory
      cortex by testing whether activity in pitch-responsive regions covaries as a
      function of pitch salience (pitch strength). A psychophysical paradigm was used
      to confirm three levels of pitch salience for two different pitch-evoking
      stimuli. The location and magnitude of the response to these stimuli were
      measured using functional magnetic resonance imaging. A pitch response was found
      in planum temporale, close to the posterolateral border of Heschl's gyrus.
      However, the response was not sensitive to pitch salience. One interpretation is
      that pitch-sensitive regions are maximally responsive to the presence or absence
      of pitch and not to pitch salience.

PMID- 21178645
TI  - Use of granulocyte colony-stimulating factor for fluorine-18-fluorodeoxyglucose
      labeling in human leukocytes.
AB  - OBJECTIVE: Insufficient labeling efficiency and poor retention of radioactivity
      are the considerable shortcomings of fluorine-18-fluorodeoxyglucose (18F-FDG)
      labeling in human leukocytes. This study was conducted to evaluate the
      feasibility of using granulocyte colony-stimulating factor (G-CSF) to improve 18F
      FDG labeling in human leukocytes. METHODS: Leukocyte separation was performed
      using methods reported earlier. Separated leukocytes were preincubated with G-CSF
      or insulin at 37 degrees C for 1 h. After preincubation, labeling was performed
      with 18F-FDG (37-74 MBq) at 37 degrees C for 30 min. Retained radioactivity was
      assessed at 1-4 h after labeling by the same method described in earlier reports.
      The viability of labeled leukocytes was assessed by 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyl tetrazolium bromide assay. RESULTS: Labeling efficiency of
      leukocytes preincubated with G-CSF, G-CSF with insulin, insulin, and control
      leukocytes was 52.1+/-8.9%, 49.9+/-10.5%, 40.3+/-7.7%, and 40.3+/-6.0%,
      respectively. G-CSF significantly increased the labeling efficiency compared with
      insulin (P=0.005) and control (P=0.004). In leukocytes preincubated with G-CSF,
      77.0+/-1.2%, and 59.0+/-1.8% of radioactivity was retained at 1 and 3 h after
      labeling. There was no significant difference in retained radioactivity compared
      with that of leukocytes with different treatment at all time points. Furthermore,
      no significant difference in viabilities among leukocytes with different
      treatments was observed. CONCLUSION: Use of G-CSF significantly improved 18F-FDG
      labeling efficiency without a significant effect on cell viability and retention
      of radioactivity.

PMID- 21178646
TI  - Can severely impaired cortical transit predict which children with pelvi-ureteric
      junction stenosis detected antenatally might benefit from pyeloplasty?
AB  - INTRODUCTION: Until recently, renogram, performed in children with pelvi-ureteric
      junction stenosis detected antenatally, has not been able to predict the
      probability of function improvement after surgery or the risk of function
      deterioration in case of conservative attitude. Recently, Schlotmann et al. have
      suggested that cortical transit might have this predictive role. The aim of this
      study, focused on those kidneys with severely impaired cortical transit, was to
      verify this statement. METHODS: All renograms performed in children during a 3
      year period (n=729) were retrospectively reviewed and 19 pediatric patients were
      selected based on an antenatally detected unilateral pelvi-ureteric junction
      syndrome, the existence of at least two renograms during the follow-up and a
      severe cortical transit impairment, visually defined. Twenty-six pairs of data
      could be analyzed and allowed comparing preoperative and postoperative
      differential renal function (DRF), and the DRF changes during the conservative
      management. RESULTS: Among the 16 patients who underwent pyeloplasty, 10 showed a
      significant DRF improvement. Among the 10 patients with conservative follow-up,
      four showed a significant DRF deterioration. CONCLUSION: Severely impaired
      cortical transit seems to be a valuable marker of those patients who could
      benefit from a pyeloplasty, either because of the high probability of
      postoperative DRF improvement, or because of DRF deterioration in case of an
      conservative approach. However, a normal cortical transit, as defined in this
      study, does not exclude the risk of DRF deterioration. Alternatively, the design
      of this study does not allow excluding the fact that DRF might improve after
      pyeloplasty despite a normal cortical transit.

PMID- 21178647
TI  - Measurement of glomerular filtration rate with chromium-51 ethylene diamino
      tetraacetic acid in the presence of gallium-67 citrate: a novel method for the
      solution of the problem.
AB  - Chromium-51 (51Cr)-ethylene diamino tetraacetic acid plasma clearance is commonly
      used in glomerular filtration rate measurements. In the presence of additional
      radionuclides in plasma samples, glomerular filtration rate may be seriously
      underestimated and a correction of the crosstalk interference may be necessary.
      This type of correction is problematic in the case of gallium-67 (67Ga) mainly
      because of the close vicinity of its 300 keV photopeak with that of the 320 keV
      photopeak of 51Cr. A novel method of calculating and removing the interfering
      67Ga counts within the 51Cr counting window, based on the different decay rates
      of the two radionuclides, is presented, requiring two series of sample counting
      in the 51Cr counting window only, separated by a 3-day interval. This method was
      developed to solve a clinical problem and then it was validated by a controlled
      67Ga contamination of plasma samples with known counts from 51Cr-ethylene diamino
      tetraacetic acid.

PMID- 21178648
TI  - Improvement of capecitabine antitumoral activity by melatonin in pancreatic
      cancer.
AB  - OBJECTIVE: The purpose of our study was to evaluate the effects of the addition
      of melatonin and capecitabine on experimental pancreatic cancer. METHODS: Fifty
      Syrian hamsters were randomized in 5 groups: group 1: no tumor induction (control
      group); group 2: tumor induction with BOP [N-nitrosobis(2-oxopropyl) amine];
      group 3: tumor induction with BOP and melatonin administration; group 4: tumor
      induction with BOP and capecitabine administration; and group 5: tumor induction
      with BOP and administration of combined capecitabine and melatonin therapy. The
      evaluation of pathological tumor evolution and oxidative stress markers in
      pancreatic tissue was carried out. RESULTS: All animals under BOP exposure
      presented poorly or moderately differentiated pancreatic adenocarcinoma
      associated with increased lipoperoxide levels and decreased antioxidant activity
      in pancreatic tissue. Pancreatic cancer was shown in only 66% of the capecitabine
      treated group and 33% of melatonin-treated group (P < 0.05), most of them
      moderately differentiated adenocarcinoma. When capecitabine and melatonin were
      combined, a well-differentiated pancreatic adenocarcinoma was observed in 10% of
      animals. The beneficial effect was associated with a decrease in lipoperoxide
      levels and increased antioxidant activity in pancreatic tissue. CONCLUSIONS: The
      combined administration of capecitabine and melatonin provided an improvement in
      antioxidant status as well as a synergistic antitumoral effect in experimental
      pancreatic cancer.

PMID- 21178649
TI  - Intraobserver agreement among endosonographers for endoscopic ultrasound features
      of chronic pancreatitis: a blinded multicenter study.
AB  - OBJECTIVE: Assess intraobserver agreement among endosonographers for endoscopic
      ultrasound (EUS) features of chronic pancreatitis (CP). METHODS: Thirty EUS
      images from patients with suspected CP were shown twice in random order to 5
      blinded endosonographers. The following accepted features of CP were assessed:
      (1) hyperechoic foci, (2) hyperechoic strands, (3) lobularity, (4) cysts, (5)
      stones, (6) main pancreatic duct dilatation, (7) pancreatic duct irregularity,
      (8) hyperechoic duct margins, (9) visible side branches, and (10) overall
      assessment for CP. Intraobserver kappa statistics were calculated for each
      endosonographer and for each feature. Interobserver kappa was also calculated.
      RESULTS: The mean intraobserver kappa values were 0.82, 0.65, 0.71, 0.59, and
      0.86 for the 5 endosonographers. The mean intraobserver kappa values for each
      feature were (1) 0.66, (2) 0.67, (3) 0.70, (4) not calculable, (5) 0.96, (6)
      0.81, (7) 0.77, (8) 0.69, (9) 0.51, and (10) 0.73. The mean interobserver kappa
      values were 0.19, 0.07, 0.53, not calculable, 0.77, 0.77, 0.60, 0.34, 0.11, and
      0.39, respectively. CONCLUSIONS: There was good intraobserver agreement in the
      interpretation of EUS features of CP. The intraobserver agreement seems better
      than the published interobserver agreement for EUS features of CP and better than
      the published intraobserver agreement for endoscopic retrograde
      cholangiopancreatography imaging for CP.

PMID- 21178651
TI  - Noninvasive quantification of pancreatic fat in healthy male population using
      chemical shift magnetic resonance imaging: effect of aging on pancreatic fat
      content.
AB  - OBJECTIVES: This study was aimed to establish a database of pancreatic fat
      fractions for healthy men aged 20 to 70 years using double-echo chemical shift
      gradient-echo magnetic resonance imaging. METHODS: The double-echo chemical shift
      gradient-echo magnetic resonance imaging technique was used in this study. A
      phantom of fat-water mixtures was established to test the accuracy of the
      sequence. In addition, 126 healthy male volunteers (20-70 years, body mass index
      <= 25) were enrolled. Fat content of the pancreas (head, body, and tail) was
      examined. RESULTS: On the phantom, a significant positive linear correlation and
      linear regression was found between the calculated and actual fat fractions of
      fat emulsions. For volunteers, there was no significant difference regarding fat
      fractions among the 3 regions of pancreata in each age group (P > 0.05).
      Pancreatic fat fraction (6.32% +/- 1.18%) of healthy men aged 50 to 70 years was
      approximately 1-fold higher than that (2.8% +/- 0.66%) of those aged 20 to 50
      years (P < 0.01). CONCLUSIONS: Double-echo chemical shift gradient-echo magnetic
      resonance imaging is useful for quantifying pancreatic fat fraction. This
      noninvasive technique has revealed (1) an even distribution of pancreatic fat in
      healthy men, (2) aging as an independent risk factor for pancreatic steatosis,
      and (3) the increase in pancreatic fat fraction beginning in the fifth decade.

PMID- 21178650
TI  - Islet cells contribute to pancreatic carcinogenesis in an animal model.
AB  - OBJECTIVES: In the hamster model, pancreatic ductal adenocarcinoma develops after
      treatment with N-nitrosobis-(2-oxopropyl)amino (BOP). In this model, Langerhans
      islets play a central role in carcinogenesis. In contrast, treatment with BOP in
      rats and mice did not result in cancer development. We investigated whether
      pancreatic tumors develop after orthotopic implantation of hamster islets into
      severe combined immunodeficiency mouse pancreases and subsequent treatment with
      BOP. This occurrence would suggest that pancreatrophic carcinogens are
      metabolized by islet cells. METHODS: Twenty-four severe combined immunodeficiency
      mice were separated into 2 groups of 12 animals. Five hundred hamster islets were
      implanted in the splenic lobe of the mouse pancreases in the treatment group,
      whereas animals of the control group received a sham operation. All animals were
      treated with BOP for 5 weeks. One year later, the animals were killed and
      investigated for tumors. RESULTS: Carcinomas developed in 3 animals in the
      treatment group and none in the control group. The tumors displayed the
      histomorphological phenotype pancreatic ductal adenocarcinoma. CONCLUSIONS: Islet
      cells seem to play a role in pancreatic carcinogenesis in this animal model and
      therefore represent useful targets for future investigations on the putative role
      of islet cells during pancreatic ductal adenocarcinoma tumorigenesis.

PMID- 21178652
TI  - Calcitonin-secreting pancreatic endocrine tumors: systematic analysis of a rare
      tumor entity.
AB  - OBJECTIVE: Pancreatic endocrine tumors (PETs) are characterized by the presence
      of hormone syndromes. Reports focusing on calcitonin-secreting PET (CTsPETs) are
      very rare. This study aimed to define a CTsPET-associated syndrome in regard to
      chemical, anatomical, and developmental aspects. METHODS: A computerized MEDLINE
      search was conducted under the search items: "pancreatic endocrine tumor,"
      "calcitonin," "neuroendocrine pancreatic tumor," and "pancreas." Results of
      clinical, histopathological, immunohistochemical, and biochemical assessments of
      all patients identified with CTsPET were registered and statistically analyzed.
      RESULTS: Thirty-seven patients with CTsPET were identified. Mean serum calcitonin
      was elevated to the 89.2-fold of the upper reference value. Main symptoms were
      watery diarrhea (51.4%) and abdominal pain (35.1%). Most patients (59.5%)
      presented with metastatic spread at the time of diagnosis. Of all patients, 66.7%
      were alive after a mean follow-up of 28.9 months. Survival was higher in patients
      who underwent more aggressive surgical therapies independent from tumor sizes and
      in those with no metastases at the time of diagnosis. CONCLUSIONS: High
      calcitonin levels should always raise suspicion of medullary thyroid carcinomas.
      However, when thyroid examination remains without pathological findings, a CTsPET
      should be excluded. An aggressive surgical approach even in cases with large
      primary tumor sizes may lead to a longer survival.

PMID- 21178653
TI  - Characterization of alternative spliceoforms and the RNA splicing machinery in
      pancreatic cancer.
AB  - OBJECTIVES AND METHODS: Alternative splicing provides proteomic diversity that
      can have profound effects. The extent, pattern, and roles of alternative splicing
      in pancreatic cancer have not been systematically investigated. We have utilized
      a spliceoform-specific microarray and polymerase chain reaction to evaluate all
      known splice variants in human pancreatic cancer cell lines representing a
      spectrum of differentiation, from near-normal HPDE6 to Capan-1 and poorly
      differentiated MiaPaCa2 cells. Validation of altered spliceoforms was verified in
      primary cancer specimens and normal pancreatic ductal cells. In addition,
      expression of 92 spliceosomal genes was examined to better understand the
      mechanism for observed differences in mRNA splicing. RESULTS: A statistically
      significant reduction in alternative splicing was found in the pancreatic cancer
      cell lines compared with HPDE6 cells. Many splice variants identified in Capan-1
      and MiaPaCa2 cells were observed in grades 3 and 4 tumors. Analysis of genes
      encoding spliceosomal proteins revealed that 28 of 92 genes had significantly
      decreased expression in cancer compared with normal pancreas. CONCLUSIONS:
      Pancreatic cancer has reduced alternative splicing diversity compared with normal
      pancreas. This is demonstrated in both cell lines and primary tumors, with the
      loss in splicing diversity correlated with relative reduction in expression of
      spliceosomal genes.

PMID- 21178654
TI  - Evaluation of adjuvanted pandemic H1N1(2009) influenza vaccine after one and two
      doses in young children.
AB  - BACKGROUND: When Canada chose an adjuvanted influenza A H1N1(2009) vaccine for
      pandemic control, dosing requirements and safety in children were unknown. This
      study compared responses after 1 and 2 doses in young children. METHODS: Five
      Canadian centers evaluated ASO3-adjuvanted H1N1(2009) vaccine (Arepanrix, GSK
      Laval, Quebec) in children aged 6 to 35 months, given 2 doses (0.25 mL, 1.9 MUg
      hemagglutinin) 21 days apart. Blood was collected at baseline and 21 to 28 days
      after each dose to measure hemagglutination inhibition antibody titers. Adverse
      events were documented daily for 7 days after each dose. RESULTS: Centers
      enrolled 167 children (mean age, 19 months). At baseline, 29 children (17.4%) had
      hemagglutination inhibition titers >= 10. After dose 1, titers >= 40 were present
      in 79.7% of initially naive subjects and 100% of initially primed subjects, whose
      respective geometric mean titers were 68 and 1020 (P < 0.001). After dose 2, 100%
      of subjects had titers >= 40, with geometric mean titers increasing to 723 in
      naive subjects and to 1854 in primed subjects (P < 0.001). Injection site
      reactions occurred in 56% of subjects after dose 1 and 43% after dose 2 (P <
      0.01), with severe reactions noted in <= 3%. Fever >39.0 degrees C was infrequent
      after either dose (5.4%, 6.6%, P = 0.20). Mild or moderate general symptoms were
      common but short-lived and less frequent after dose 2. CONCLUSIONS: One dose of
      adjuvanted vaccine met criteria for licensing seasonal influenza vaccines. A
      second dose increased titers substantially, potentially affording greater or more
      durable protection. Adverse effects were common but tolerable. The use of
      adjuvanted seasonal influenza vaccines in young children merits consideration.

PMID- 21178655
TI  - Safety and pharmacokinetics of a single 1500-mg dose of famciclovir in
      adolescents with recurrent herpes labialis.
AB  - An open-label study evaluated the safety (n = 53) and pharmacokinetics (n = 8) of
      single-dose therapy with 1500 mg famciclovir (prodrug of penciclovir) for
      recurrent herpes labialis in adolescents. Mean Cmax, mean AUC0-infinity, and
      clearance for penciclovir were 9.37 MUg/mL, 31.8 MUg . h/mL, and 38.2 L/h,
      respectively, and within the range extrapolated from data in adults. Adverse
      events were generally mild and transient.

PMID- 21178656
TI  - Detection of human papillomavirus in bronchoalveolar lavage samples in
      immunocompetent children.
AB  - BACKGROUND: Human papillomavirus (HPV) has been detected in lungs of adults and
      has been proposed to play a role in lung carcinogenesis. However, no data are
      currently available on the incidence of HPV in the lower respiratory tract of
      children. PURPOSE: To determine the prevalence of HPV deoxyribonucleic acid (DNA)
      in bronchoalveolar lavage (BAL) samples were obtained from asymptomatic
      immunocompetent children. METHODS: A total of 71 children between 2 and 12 years
      of age were prospectively enrolled. Detection of HPV DNA and HPV typing were
      performed using polymerase chain reaction-based techniques. RESULTS: Of the 71
      BAL samples, HPV DNA was detected in 6 children. Coinfection with HPV 16, 18, and
      31 was detected in 2 children, while 4 children were positive for non-"high-risk"
      HPVs. CONCLUSIONS: This preliminary case-control study indicates the presence of
      HPV DNA in BAL samples in children. The possible presence of HPV in the lower
      respiratory tract of children requires further investigation to elucidate the
      actual epidemiologic condition, the potential modes of its transmission, and its
      possible causative relationship in lung carcinogenesis in adulthood.

PMID- 21178657
TI  - In vivo safety of trypan blue use in vitreoretinal surgery.
AB  - PURPOSE: The purpose of this study was to evaluate "in vivo" safety of trypan
      blue (TB) in patients undergoing TB-assisted internal limiting membrane or
      epiretinal membrane peeling. METHODS: Prospective study including 21 patients (21
      eyes) with full-thickness macular hole and/or epiretinal membrane undergoing TB
      assisted internal limiting membrane/epiretinal membrane peeling. Main outcome
      measures included distance visual acuity, near visual acuity, amplitude of P50
      and N95 of the pattern electroretinogram, and fundus autofluorescence; these were
      assessed preoperatively, at 6 months (n = 21) and 12 months (n = 10)
      postoperatively. RESULTS: There was a statistically significant improvement in
      distance visual acuity, near visual acuity, P50, and N95 amplitude at 6 months
      and 12 months postoperatively. The mean logarithm of the minimum angle of
      resolution distance visual acuity and near visual acuity improved from baseline
      by 0.31 (SD 0.37) and 0.17 (SD 0.31) at 6 months, respectively, and by 0.4 (SD
      0.25) and 0.35 (SD 0.28) at 12 months, respectively. The mean P50 and N95
      component amplitudes improved by 28% compared with baseline at 6 months (P50 0.4
      [SD 0.8]; N95 0.53 [SD 1.07]) and by 63% at 12 months (P50 0.9 [0.85]; N95 1.04
      [1.34]). Autofluorescence did not demonstrate damage to the retinal pigment
      epithelium attributable to TB. CONCLUSION: No deleterious effects of TB were
      observed in this study.

PMID- 21178658
TI  - Long-term trends in intraocular pressure after pars plana vitrectomy.
AB  - PURPOSE: To evaluate the effect of vitrectomy on intraocular pressure (IOP).
      METHODS: Retrospective cohort study. Medical records of 101 eyes of 101 patients
      undergoing nonemergent vitrectomy were reviewed for rates of open-angle glaucoma,
      increased IOP of >4 mmHg from baseline, change in IOP from baseline, and cataract
      formation. Preoperative and last measured IOPs were recorded. Baseline risk
      characteristics including lens status and diabetes were analyzed. Main outcome
      measures were 1) incidence of open-angle glaucoma; 2) increase in IOP of >4 mmHg;
      and 3) change in IOP. RESULTS: Mean follow-up was 49 months (range, 12-105
      months). Mean baseline IOP was 15.3 mmHg, and mean final IOP was 15.8 mmHg (P =
      0.3). At the most recent examination, 35 study eyes had a decrease in IOP from
      baseline, while 14 eyes had no change and 52 eyes had an increase in IOP. Four
      study eyes were newly diagnosed with ocular hypertension. No study eye developed
      open-angle glaucoma or required medical, laser, or surgical treatment for
      glaucoma. Incidence of increased IOP of >4 was 7% at 4 years and 34% at 8 years.
      Subgroup analysis of 66 patients comparing study eyes with nonvitrectomized
      fellow eyes demonstrated no significant difference in rates of increased IOP of
      >4 (P = 0.85). Neither diabetes nor pseudophakia was associated with
      significantly increased IOP. CONCLUSION: In this series, vitrectomy does not
      appear to increase IOP even after removal of the crystalline lens.

PMID- 21178659
TI  - Incidence of endophthalmitis after intravitreal injection of antivascular
      endothelial growth factor medications using topical lidocaine gel anesthesia.
AB  - PURPOSE: The purpose of this study was to determine the incidence of infectious
      endophthalmitis after intravitreal injection of antivascular endothelial growth
      factor medications using 2% topical lidocaine gel anesthesia. METHODS:
      Retrospective chart review of 4690 consecutive intravitreal injections of
      antivascular endothelial growth factor medications using 2% topical lidocaine gel
      anesthesia. All patients had at least 6 weeks of follow-up. RESULTS: A total of
      608 patients underwent intravitreal injection of antivascular endothelial growth
      factor medications during the study period. There were 428 injections of
      pegaptanib sodium, 1841 injections of bevacizumab, and 2421 injections of
      ranibizumab. There were no cases of infectious endophthalmitis. The per-injection
      infection rate was 0.0% (95% confidence interval, 0.0-0.06%). CONCLUSION: The
      incidence of infectious endophthalmitis after intravitreal injection of
      antivascular endothelial growth factor medications using 2% topical lidocaine gel
      anesthesia is low.

PMID- 21178660
TI  - Atherosclerotic and thrombophilic risk factors in patients with ischemic central
      retinal vein occlusion.
AB  - PURPOSE: To investigate atherosclerotic and thrombophilic risk factors in
      patients affected by acute ischemic and nonischemic central retinal vein
      occlusions (CRVOs). METHODS: One hundred and three patients with acute unilateral
      CRVO (41 ischemic and 62 nonischemic) were studied. The frequency of traditional
      cardiovascular risk factors was assessed, and the plasma levels of a variety of
      thrombophilic markers were measured. Univariate logistic regression was performed
      to determine risk factors for ischemic CRVO. RESULTS: Arterial hypertension,
      hypercholesterolemia, postmethionine hyperhomocysteinemia (HHcy), elevated factor
      VIII, and reduced folic acid and B6 plasma levels were more frequent in patients
      with ischemic CRVO than in those with nonischemic CRVO (P = 0.030, P = 0.025, P =
      0.011, P < 0.001, P < 0.001, and P = 0.044, respectively). Risk factors for
      ischemic CRVO were arterial hypertension (odds ratio [OR], 3.22; 95% confidence
      interval [CI], 1.13-9.21; P = 0.037), hypercholesterolemia (OR, 3.03; 95% CI,
      1.06-8.65; P = 0.042), reduced folic acid levels (OR, 6.77; 95% CI, 1.59-28.79; P
      = 0.011), and elevated FVIII levels (OR, 6.17; 95% CI, 2.56-14.82; P < 0.001).
      Postmethionine HHcy was associated with low folic acid levels (r = -0.413; P =
      0.007; OR, 9.33; 95% CI, 2.06-42.18; P = 0.005). CONCLUSION: The results of the
      present study suggest that some atherosclerotic and thrombophilic risk factors
      may increase the risk of having an ischemic form of CRVO.

PMID- 21178663
TI  - Neuroimaging in geriatric psychiatry: integrative research as the next frontier.

PMID- 21178667
TI  - Cerebral oximetry: monitoring the brain as the index organ.

PMID- 21178669
TI  - Preoperative cerebral oxygen saturation and clinical outcomes in cardiac surgery.
AB  - BACKGROUND: The current study was designed to determine the relation between
      preoperative cerebral oxygen saturation (Sco2), variables of cardiopulmonary
      function, mortality, and morbidity in a heterogeneous cohort of cardiac surgery
      patients. METHODS: In this study, 1,178 consecutive patients scheduled for on
      pump surgery were prospectively studied. Preoperative Sco2, demographics, N
      terminal pro-B-type natriuretic peptide, high-sensitive troponin T, clinical
      outcomes, and 30-day and 1-yr mortality were recorded. RESULTS: Median additive
      EuroSCORE was 5 (range: 0-19). Thirty-day and 1-yr mortality and major morbidity
      (at least two major complications and/or a high-dependency unit stay of at least
      10 days) were 3.5%, 7.7%, and 13.3%, respectively. Median minimal preoperative
      oxygen supplemented Sco2 (Sco2min-ox) was 64% (range: 15-92%). Sco2min-ox was
      correlated (all: P value <0.0001) with N-terminal pro-B-type natriuretic peptide
      (rho: -0.35), high-sensitive troponin T (rho: -0.28), hematocrit (rho: 0.34),
      glomerular filtration rate (rho: 0.19), EuroSCORE (tau: 0.20), and left
      ventricular ejection fraction class (tau: 0.12). Thirty-day nonsurvivors had a
      lower Sco2min-ox than survivors (median 58% [95% CI, 50.7-62%] vs. 64% [95% CI,
      64-65%]; P < 0.0001). Receiver-operating curve analysis of Sco2min-ox and 30-day
      mortality revealed an area-under-the-curve of 0.71 (95% CI, 0.68-0.73%; P <
      0.0001) in the total cohort and an area-under-the-curve of 0.77 (95% CI, 0.69
      0.86%; P < 0.0001) in patients with a EuroSCORE more than 10. Logistic regression
      based on different EuroSCORE categories (0-2; 3-5, 6-10, >10), Sco2min-ox, and
      duration of cardiopulmonary bypass showed that a Sco2min-ox equal or less than
      50% is an independent risk factor for 30-day and 1-yr mortality. CONCLUSIONS:
      Preoperative Sco2 levels are reflective of the severity of cardiopulmonary
      dysfunction, associated with short- and long-term mortality and morbidity, and
      may add to preoperative risk stratification in patients undergoing cardiac
      surgery.

PMID- 21178671
TI  - Impact of preoperative statin therapy on adverse postoperative outcomes in
      patients undergoing vascular surgery.
AB  - BACKGROUND: Chronic statin therapy is associated with reduced postoperative
      mortality. Renal and cardiovascular benefits have been described, but the effect
      of chronic statin therapy on postoperative adverse events has not yet been
      explored. METHODS: In this observational study involving 1,674 patients
      undergoing aortic reconstruction, we prospectively assessed chronic statin
      therapy compared with no statin therapy, with regard to serious outcomes, by
      propensity score and multivariable methods. RESULTS: In propensity-adjusted
      multivariable logistic regression (c-index: 0.83), statins were associated with
      an almost threefold reduction in the risk of death in patients undergoing major
      vascular surgery (odds ratio: 0.40; 95% CI: 0.28-0.59) and an almost twofold
      reduction in the risk of postoperative myocardial infarction (odds ratio: 0.52;
      95% CI: 0.38-0.71). Likewise, the use of chronic statin therapy was associated
      with a reduced risk of postoperative stroke and renal failure. Statins did not
      significantly reduce the risk of pneumonia, multiple organ dysfunction syndrome,
      and surgical complications; however, in the case of postoperative multiple organ
      dysfunction syndrome (odds ratio: 0.34; 95% CI: 0.12-0.94) and surgical
      complications (odds ratio: 0.39; 95% CI: 0.17-0.86), reduced mortality was
      observed. CONCLUSIONS: Chronic statin therapy was associated with a reduction in
      all cardiac and vascular outcomes after major vascular surgery. Furthermore, in
      major adverse events, such as multiple organ dysfunction syndrome and surgical
      complications, statins were also associated with decreased mortality.

PMID- 21178674
TI  - High incidence of burnout in academic chairpersons of anesthesiology: should we
      be taking better care of our leaders?
AB  - BACKGROUND: Burnout is a work-related psychologic syndrome characterized by
      emotional exhaustion, low personal accomplishment, and depersonalization.
      METHODS: By using an instrument that included the MBI-HHS Burnout Inventory, we
      surveyed academic anesthesiology chairpersons in the United States. Current level
      of job satisfaction compared with 1 and 5 yr before the survey, likelihood of
      stepping down as chair in the next 2 yr, and a high risk of burnout were the
      primary outcomes. RESULTS: Of the 117 chairs surveyed, 102 (87%) responded. Nine
      surveys had insufficient responses for assessment of burnout. Of 93 chairs, 32
      (34%) reported high current job satisfaction, which represented a significant
      decline compared with that reported for 1 yr (P = 0.009) and 5 yr (P = 0.001)
      before the survey. Of 93 chairs, 26 (28%) reported extreme likelihood of stepping
      down as a chair in 1-2 yr. There was no association of age (P = 0.16), sex (P =
      0.82), or self-reported effectiveness (P = 0.63) with anticipated likelihood of
      stepping down, but there was a negative association between the modified efficacy
      scale scorhorgr; = -0.303, P = 0.003) and likelihood of stepping down. Of 93
      chairs, 26 (28%) met the criteria for high burnout and an additional 29 (31%) met
      the criteria for moderately high burnout. Decreased current job satisfaction and
      low self-reported spousal/significant other support were independent predictors
      of high burnout risk. CONCLUSION: Fifty-one percent of academic anesthesiology
      chairs exhibit a high incidence/risk of burnout. Age, sex, time as a chair, hours
      worked, and perceived effectiveness were not associated with high burnout;
      however, low job satisfaction and reduced self-reported spousal/significant other
      support significantly increased the risk.

PMID- 21178675
TI  - Risk of burnout in perioperative clinicians: a survey study and literature
      review.
AB  - BACKGROUND: Burnout can lead to health and psychologic problems and is apparently
      increasing in physicians and nurses. Previous studies have not evaluated all
      healthcare workers within a single work unit. This study evaluates the risk of
      burnout in all medical personnel in one perioperative unit. METHODS: We developed
      an online survey that included demographics, a modified version of the Maslach
      Burnout Inventory-Human Services Survey, and the Social Support and Personal
      Coping Survey. Survey constructs (e.g., depersonalization and health) and a
      global score were calculated. Larger construct and global values were associated
      with higher risk of burnout. These were separately regressed on role, age, and
      sex. The global score was then regressed on each of the survey constructs.
      RESULTS: Of the 145 responses, 46.2% were physicians (22.8% residents), 43.4%
      were nurses or nurse anesthetists, and 10.3% were other personnel. After
      adjusting for sex and age, residents scored higher than other physicians on the
      following (expected change [95% confidence interval]): global score (1.12 [0.43
      1.82]), emotional exhaustion (1.54 [0.44-2.60]), and depersonalization (1.09
      [0.23-1.95]). Compared with nonphysicians, residents were 1 U or more higher on
      these items (P < 0.05 in all cases). Residents had higher health (1.49 [0.48
      2.50]) and workload (1.23 [0.07-2.40]) values compared with physicians. Better
      health, personal support, and work satisfaction scores were related to decreased
      global scores (P < 0.05). CONCLUSIONS: Physicians (particularly residents) had
      the largest global burnout scores, implying increased risk of burnout. Improving
      overall health, increasing personal support, and improving work satisfaction may
      decrease burnout among perioperative team members.

PMID- 21178677
TI  - Issues regarding propofol concentrations within the clinical range.

PMID- 21178678
TI  - Opioid modeling of central respiratory drive must take upper airway obstruction
      into account.

PMID- 21178681
TI  - Multiples of minimal alveolar concentration of volatile agents are not
      necessarily equipotent.

PMID- 21178682
TI  - It is time to abandon atlanto-axial joint injections: do no harm!

PMID- 21178683
TI  - Complications of C1-C2 facet injection.

PMID- 21178684
TI  - Why no casopitant-only arm?

PMID- 21178690
TI  - Auxology and obesity.

PMID- 21178691
TI  - Gastrointestinal regulatory peptides.

PMID- 21178692
TI  - Current world literature.

PMID- 21178693
TI  - It was such a year.

PMID- 21178694
TI  - Keratoconus association with axial myopia: a prospective biometric study.
AB  - OBJECTIVES: To determine if the axial length and its components are significantly
      different between a keratoconic eye and an emmetropic eye and also to determine
      if the degree of corneal ectasia is associated with axial myopia in a keratoconic
      eye. METHODS: A prospective observational study was conducted with keratoconic
      patients and emmetropic controls. All subjects underwent corneal topography
      analysis and axial length measurement by immersion-ultrasound biometry.
      Statistical methods were employed to compare the two groups and to ascertain
      whether any associations exist. RESULTS: The axial length, anterior chamber
      depth, and posterior segment length were all significantly longer in the
      keratoconic group (n=41) than in the emmetropic control group (n=33) in a
      statistically significant fashion. The mean keratoconic axial length was 24.40
      vs. 23.24 mm for the emmetropic group (P=0.001). The mean keratometry for the
      keratoconic group correlated with spherical equivalence and visual acuity in
      statistically significant manners but not with axial length. CONCLUSIONS:
      Keratoconic eyes have on average longer axial lengths that are primarily because
      of longer posterior segment lengths than emmetropic eyes. This finding should be
      considered in keratoconic patients undergoing keratoplasty because it relates to
      postkeratoplasty refractive outcomes.

PMID- 21178695
TI  - Endothelial image quality after descemet stripping with endothelial keratoplasty:
      a comparison of three microscopy techniques.
AB  - PURPOSE: To determine corneal endothelial image quality after descemet stripping
      with endothelial keratoplasty (DSEK) as recorded by three different microscopy
      techniques: noncontact specular microscopy, noncontact confocal microscopy, and
      contact confocal microscopy. METHODS: The corneal endothelium of 52 eyes after
      DSEK and 20 normal eyes was photographed by the three microscopy techniques
      during a single encounter. Image quality was graded by two masked observers
      according to the proportion of countable contiguous cells visible in the image;
      disagreements in grading were adjudicated by a third observer. Endothelial cell
      density was compared among the three techniques. RESULTS: After DSEK, image
      quality was better with contact confocal microscopy than with noncontact confocal
      microscopy (P = 0.01) and better with noncontact confocal microscopy than with
      noncontact specular microscopy (P < 0.001). With noncontact specular microscopy,
      42% of images after DSEK were uncountable. In normal corneas, all images were
      countable, and although image quality was better with contact confocal microscopy
      than with noncontact confocal (P = 0.03) and noncontact specular (P < 0.001)
      microscopy, the difference was not clinically important. For countable images,
      the mean differences in endothelial cell density between microscopy methods were
      close to zero after DSEK and in normal corneas. CONCLUSIONS: Confocal optics
      enable better image quality of the corneal endothelium in corneas with high
      backscatter, such as those after DSEK. When images were countable, there was a
      good agreement for endothelial cell density measured by the three microscopy
      techniques.

PMID- 21178696
TI  - Prevalence of astigmatism in relation to soft contact lens fitting.
AB  - PURPOSE: To estimate the proportion of potential soft contact lens wearers
      requiring an astigmatic correction and to estimate the proportion of astigmats
      who can be accommodated with toric soft lenses of varying prescription range.
      METHOD: A database of 11,624 spectacle prescriptions was used to calculate the
      prevalence of astigmatism for various thresholds (0.50-2.00 DC) by eye and by
      patient. The coverage of various prescription ranges was estimated using a subset
      of the database comprising those patients with at least 0.75 D of astigmatism in
      at least one eye (n = 5,444). RESULTS: The prevalence of patients showing
      astigmatism of 0.75 and 1.00 D or greater in at least one eye was 47.4% and 31.8%
      and, in both eyes, 24.1% and 15.0%, respectively. The proportion of eyes showing
      astigmatism greater than or equal to 0.75, 1.00, 1.50, and 2.00 D was 35.7%,
      23.4%, 10.8%, 5.6%, respectively. The prevalence of astigmatism of 0.75 D or
      greater was almost double in myopes compared with hyperopes: 31.7% vs. 15.7%. The
      prevalence of with-the-rule (WTR) astigmatism was higher than against-the-rule
      (32.9% vs. 29.1%); the proportion was also higher for WTR in eyes with
      astigmatism >=0.75 D (15.3% vs. 14.5%). We estimate that approximately one third
      of potential contact lens wearers require astigmatic correction. A stock range of
      toric soft lenses in sphere powers +6.00 to -9.00 D, three cylinder powers, and
      18 axes requires nearly 3,000 prescriptions and provides coverage for 90% of
      astigmats. CONCLUSION: These findings provide an estimate of the proportion of
      soft contact lens patients requiring an astigmatic correction and some useful
      insights into the proportion of astigmats covered by toric soft lens stocks of
      varying range.

PMID- 21178697
TI  - Corneal refractive therapy gas permeable lenses for the correction of hyperopia
      after one night of lens wear.
AB  - PURPOSE: To examine the refractive and keratometric response of corneal
      refractive therapy (CRT) contact lenses for hyperopia (CRT) after a single night
      of contact lens wear with the goal of reducing hyperopia by +3.50 D. METHOD:
      Twenty participants were fitted with a CRT HDS 100 contact lens, in one eye only.
      The back optic zone radius of the CRT lens was designed to correct 3.50 D of
      hyperopia. The eyes were randomly selected. The Nikon Auto Refractor was used to
      measure refractive error. Corneal topography and simulated K readings were
      measured using the Humphrey Atlas topographer. The lens was subsequently worn
      overnight, and the lens was assessed the next morning on awakening. RESULTS:
      Refractive error changed by 1.50+/-0.71 D (mean +/- SD, range 0.50-2.75 D)
      immediately after lens removal in the experimental eye. Similarly, there was a
      change in flat K readings of 0.58+/-0.62 D with a range of -0.25 to +1.87 D.
      These results were significantly different from the baseline measurements
      (P<0.0001). CONCLUSIONS: The fitting of CRT HDS for hyperopia has a significant
      effect on corneal shape and refractive error. There was a moderate yet
      significant steepening of the cornea.

PMID- 21178698
TI  - Severity and determinants of pinguecula in a hospital-based population.
AB  - OBJECTIVES: Pinguecula is a relatively frequent disease; however, there have been
      no reports about the grade of pinguecula. We investigated the relationship
      between age and the prevalence and severity of pinguecula by using a grading
      system and compared the grade of pinguecula between men and women and between the
      nasal and temporal halves of the conjunctiva. METHODS: This was a prospective,
      randomized study of 1,040 patients aged 1 to 95 years, including 520 men and 520
      age-matched women. The age, gender, medical history, ocular history, and grade of
      pingueculae located on the nasal and temporal conjunctiva were determined in all
      subjects. RESULTS: The prevalence of pinguecula increased dramatically with age.
      The mean grade was higher in male patients than in female patients for
      pingueculae located on both the nasal conjunctiva (P = 0.00072) and the temporal
      conjunctiva (P = 0.00035). However, there was no significant difference in the
      grade of pinguecula between the nasal and temporal conjunctiva. CONCLUSIONS: This
      was the first assessment of the grade of pinguecula in a large series of
      patients. Our findings strongly suggest that pinguecula is an age-dependent
      lesion that occurs from young adulthood onward. The present grading system should
      also be useful for future clinical studies of pinguecula.

PMID- 21178699
TI  - Long-term use of hydroxypropyl cellulose ophthalmic insert to relieve symptoms of
      dry eye in a contact lens wearer: case-based experience.
AB  - OBJECTIVES: To report a case in which hydroxypropyl cellulose ophthalmic inserts
      were successfully used for the treatment of dry eye disease in a contact lens
      (CLs) wearer for more than 25 years. METHODS: Review of clinical findings in a
      female CL wearer with dry eye spanning more than 30 years. The patient was
      diagnosed with the Sjogren syndrome and demonstrated inadequate lacrimation as
      assessed by Schirmer testing. Slitlamp examination demonstrated bilateral corneal
      stippling with fluorescein and signs of superior limbic keratoconjunctivitis.
      RESULTS: Initially, the patient's symptoms improved with infrequent use of
      artificial tears. As the signs and symptoms of dry eye disease worsened, the
      patient initiated therapy with once-daily hydroxypropyl cellulose ophthalmic
      inserts. Punctal plugs and updating to increasingly oxygen-permeable soft CLs, in
      combination with continued use of the inserts, largely controlled the signs and
      symptoms of dry eye disease during a 25-year period. Simultaneous use of the
      hydroxypropyl cellulose ophthalmic inserts and CLs was well tolerated without any
      significant side effects or changes in visual acuity. CONCLUSIONS: Dry eye is a
      chronic disease often requiring long-term management. In this case, daily use of
      hydroxypropyl cellulose ophthalmic inserts effectively treated autoimmune dry
      eye, providing symptomatic relief, and resulted in improved objective measures of
      disease severity across several decades. Such an experience is consistent with
      the available evidence-based data for hydroxypropyl cellulose ophthalmic inserts
      and supports their use in clinical practice for the treatment of moderate-to
      severe dry eye disease.

PMID- 21178703
TI  - Creatinine as a measure of lean body mass during treatment of acute lymphoblastic
      leukemia in childhood.
AB  - Protein energy malnutrition is well-recognized in children with acute leukemia
      and may result in loss of lean body mass (LBM) with attendant morbidities. Much
      of the LBM consists of skeletal muscle, the mass of which is reflected in urinary
      creatinine excretion. As accurate 24 hours urine collections are challenging in
      children, we investigated the prospect that serum creatinine concentration
      provides a measure of LBM. Eleven children with acute lymphoblastic leukemia were
      assessed at 7 time points (6-mo intervals) from diagnosis to 1 year after the
      completion of therapy. LBM was measured as fat-free mass by dual energy x-ray
      absorptiometry (DXA scans) and correlated with serum creatinine concentration and
      24 hours urine creatinine excretion. As expected, there was a strong correlation
      between 24 hours urinary creatinine excretion and LBM from DXA scans (r=0.79,
      P<0.001). Serum creatinine concentration also correlated with LBM (r=0.52,
      P<0.001). Serum creatinine concentration provides a surrogate measure of LBM in
      children with acute lymphoblastic leukemia. This will be especially useful in
      countries with limited resources in which more sophisticated measures, such as
      DXA scans, are seldom available.

PMID- 21178704
TI  - Clinical features and outcome of 2009 influenza A (H1N1) virus infections in
      children with malignant diseases: a case-control study.
AB  - BACKGROUND: The impact of the novel 2009 influenza A (H1N1) (2009 H1N1) virus in
      children with malignant diseases under therapy is not well known. OBJECTIVE: To
      analyze the clinical features and outcome in children with anticancer therapy
      infected with the 2009 H1N1 virus. PATIENTS AND METHODS: Descriptive, case
      control study. Between May and July 2009, 24 cases of 2009 (H1N1) virus
      infections in children with malignant diseases were registered and 48 control
      cases of similar patients infected with common influenza A virus (IA) diagnosed
      between 2006 and 2008 were selected. RESULTS: Median age for cases was 72 months
      and for controls was 83 months (P >= 0.05). Children with IA showed neutropenia
      more frequently (52% vs. 17%), longer period of time with illness before
      diagnosis (3 d vs. 1.7 d), higher rate of earlier medical consultation (69% vs.
      25%), and more antibiotic therapy courses (54% vs. 4%; P <= 0.05) than patients
      with 2009 H1N1 virus. Children infected with this virus presented hypoxemia more
      frequently (42% vs. 8%) and higher rates of intensive care unit hospitalizations
      (29% vs. 2%; P <= 0.05). Three children with 2009 H1N1 virus and 1 in the control
      group died. CONCLUSIONS: Children infected with 2009 H1N1 virus presented more
      morbidity and mortality than patients infected with seasonal IA virus.

PMID- 21178705
TI  - Comparing abstract numerical and visual depictions of risk in survey of parental
      assessment of risk in sickle cell hydroxyurea treatment.
AB  - Communicating risk is an important activity in medical decision-making; yet,
      numeracy is not a universal skill among the American public. We examined the
      hypothesis that numerical risk information about the use of hydroxyurea for
      children with sickle cell disease would elicit different risk assessment
      responses when visual depictions were used instead of abstract numbers and
      depending on the disease severity. Parents of 81 children with sickle cell
      disease participated in a survey in which hydroxyurea was first described as
      carrying a certain chance of risk for both birth defects and cancer. Then, the
      parents indicated the highest risk at which they would hypothetically consent to
      the treatment to help their child. Risk presentations were repeated with abstract
      numerical, pie graph, and 1000 people histogram formats. The chi analyses
      comparing high-risk to low-risk assessment across presentation formats showed
      high consistency between visual depictions but low consistency of abstract
      numerical with visual depictions. The parents of children with SC and other less
      severe types of SCD were less willing to accept higher risk than those with SS
      when the data were presented numerically. Given earlier concerns about poor
      "numeracy" in the US population, visual depictions of risk could be an effective
      tool for routine communication in health education and medical decision-making.

PMID- 21178706
TI  - Precursor-T lymphoblastic lymphoma after unrelated bone marrow transplantation in
      a patient with Fanconi anemia.
AB  - Lymphoid malignancies are rare in patients with Fanconi anemia (FA), particularly
      after bone marrow transplantation. A boy, who was diagnosed with FA at the age of
      5; underwent successful bone marrow transplantation at the age of 11. One year
      later, he presented with fever and dry cough, and was found to have an anterior
      mediastinal tumor. Biopsy of the tumor revealed precursor-T cell lymphoblastic
      lymphoma. Human leukocyte antigen analysis confirmed that the tumor cells were
      derived from the patient's own cells. He received mild chemotherapy for lymphoma,
      but his condition deteriorated rapidly and he died from excessive chemotherapy
      related toxicity. The literature contains no reports of successful chemotherapy
      for lymphoid tumors in patients with FA, and therefore, alternatives to
      chemotherapy should be considered in the treatment of such patients.

PMID- 21178707
TI  - Early intraoperative blood collection does not affect complete blood counts, von
      Willebrand factor or factor VIII levels in normal children.
AB  - BACKGROUND: Obtaining blood from children for research studies can be difficult,
      particularly for controls. One solution is to obtain samples during elective
      surgery; however, consideration must be given to the potential effects of the
      timing of phlebotomy. OBSERVATIONS: Ten children were recruited and phlebotomy
      was carried out during a preoperative clinic visit and intraoperatively
      immediately after the induction of anesthesia but before the start of surgery.
      CBCs, VWF, and FVIII levels were measured at both time points and no significant
      differences were seen. CONCLUSIONS: This negative result may be beneficial to
      pediatric research by suggesting that early intraoperative blood collection for
      controls does not affect the results.

PMID- 21178708
TI  - Examining the origin of posttransplant lymphoproliferative disorder in a patient
      after a second allogeneic hematopoeitic stem cell transplantation for relapsed
      BCR-ABL positive acute lymphoblastic leukemia.
AB  - BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a serious
      complication because of the reactivation of the Epstein-Barr virus (EBV).
      Although after solid organ transplantation (SOT) EBV is typically of recipient
      origin, after hematopoietic stem cell transplantation (HSCT) donor-derived B
      cells are usually the source of the EBV-induced lymphoproliferation. OBSERVATION:
      We report a unique presentation of an EBV-associated PTLD in a 13-year-old boy
      who underwent 2 subsequent HSCTs from 2 different-sex donors for BCR-ABL-positive
      acute lymphoblastic leukemia (ALL) and relapses of leukemia, respectively. The
      PTLD tissue was analyzed for the origin of both B cells and T cells of the
      lesion. Chimerism analysis done with short tandem repeat systems (STR) showed no
      autologous signals; approximately 50% of the cells were from the first and second
      donors, respectively. XY-fluorescence in situ hybridization showed a B-cell PTLD
      originating from the first donor surrounded by T cells from the second donor.
      CONCLUSION: This case shows that EBV-infected B cells from a first donor can be
      the source of a PTLD after a second myeloablative HSCT from a different donor.

PMID- 21178709
TI  - Immunosuppressant-induced endothelial damage and pulmonary arterial hypertension.
AB  - Cyclosporine A, used to prevent graft-versus-host-disease, is known to induce
      endothelial injury. Endothelial dysfunction is an important feature of pulmonary
      arterial hypertension (PAH). In this article, we describe 2 children who
      developed cyclosporine-induced acute respiratory distress syndrome. Lung biopsy
      showed patchy loss of endothelial caveolin-1 and von Willebrand factor to occur
      early. Significant loss of endothelial caveolin-1 was associated with robust
      expression of caveolin-1 in smooth muscle cells with subsequent neointima
      formation leading to fatal PAH. Thus, patients who develop acute respiratory
      distress syndrome after immunosuppressive therapy are at risk of developing PAH.

PMID- 21178710
TI  - Pediatric myelodysplastic syndrome with cytoplasmic vacuolation in myeloid
      precursors.
AB  - A 6-year-old boy presented with pancytopenia. Bone marrow morphology showed
      dyspoiesis and cytoplasmic vacuolation in myeloid precursor cells. Cytoplasmic
      vacuoles are described in erythroid cells in myelodysplastic syndrome (MDS) but
      are extremely rare in myeloid precursor cells. We ruled out viral and autoimmune
      etiology, hypocupremia, Pearson syndrome, and chromosomal abnormalities. Finally,
      a diagnosis of MDS of refractory cytopenia of childhood subtype was made. The
      patient then underwent an allogenic stem cell transplant that resulted in
      normalization of the complete blood counts and bone marrow morphology. However,
      he later developed late graft failure; this was followed by a second transplant
      after which he died of sepsis and multiorgan failure. The case is presented here
      for the rare morphologic features, hitherto not earlier described in pediatric
      MDS.

PMID- 21178711
TI  - State of the journal: 2011.

PMID- 21178713
TI  - Measures of interrater agreement.
AB  - Kappa statistics is used for the assessment of agreement between two or more
      raters when the measurement scale is categorical. In this short summary, we
      discuss and interpret the key features of the kappa statistics, the impact of
      prevalence on the kappa statistics, and its utility in clinical research. We also
      introduce the weighted kappa when the outcome is ordinal and the intraclass
      correlation to assess agreement in an event the data are measured on a continuous
      scale.

PMID- 21178712
TI  - GPC5 gene and its related pathways in lung cancer.

PMID- 21178714
TI  - Epidermal growth factor receptor mutations in small cell lung cancer: a brief
      report.
AB  - INTRODUCTION: Knowledge about the current status of the epidermal growth factor
      receptor (EGFR) has resulted in an improvement in the treatment of non-small cell
      lung cancer. In contrast, small cell lung cancer (SCLC) continues to frustrate
      clinicians with its tendency toward early metastasis and chemotherapy resistance.
      Recent studies have reported the EGFR mutation and its response to gefitinib
      treatment in SCLC. We would like to share our experience of EGFR studies on SCLC
      patients. METHODS: Between 2004 and 2009, we prospectively collected 76 specimens
      from patients with SCLC at the National Taiwan University Hospital, Taiwan. These
      specimens included 10 computed tomography-guided biopsy specimens, 17 echo-guided
      aspiration specimens, 37 echo-guided biopsy specimens, 1 surgical lobectomy
      specimen, and 11 malignant pleural effusion specimens. Molecular genetic analysis
      of the specimens was conducted to detect the EGFR mutation. RESULTS: Among the 76
      SCLC specimens we examined, 2 (2.6%) tested positive for the EGFR mutation and
      both were deletions in exon 19. One patient was administered gefitinib after
      several lines of chemotherapy but showed no treatment response. To date, only 11
      EGFR mutant-positive SCLC patients, including our 2 patients, have been reported.
      Most of these patients were never smokers. The SCLC harboring EGFR mutation were
      more likely to be combined with adenocarcinoma compared with the whole SCLC
      population. CONCLUSIONS: The EGFR mutation is rare in SCLC patients. Despite the
      presence of the EGFR mutation, gefitinib may not be effective in treating SCLC
      patients.

PMID- 21178715
TI  - Miliary never-smoking adenocarcinoma of the lung: strong association with
      epidermal growth factor receptor exon 19 deletion.
AB  - Miliary pattern of pulmonary metastases is a rarity in patients with lung cancer.
      We report five cases of patients with a never-smoking adenocarcinoma of the lung
      with such a pattern of metastases. In the tumor cells of all five patients,
      epidermal growth factor receptor (EGFR) mutation gene sequencing identified a
      deletion in exon 19 of the EGFR gene, and all five patients had a dramatic
      response to EGFR tyrosine kinase inhibitors. No echinoderm microtubule-associated
      protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) translocation was
      detected. We believe that the miliary never-soking adenocarcinoma of the lung is
      a distinct clinically relevant subgroup of the never-smoking non-small cell lung
      cancer. Physician should recognize this subgroup of patients with lung cancer
      when facing a picture of miliary pulmonary metastases in chest x-ray or computed
      tomography scan in patients with a history of never smoking and consider upfront
      therapy with EGFR tyrosine kinase inhibitors.

PMID- 21178716
TI  - How I do it--optimal methodology for multidirectional analysis of endobronchial
      ultrasound-guided transbronchial needle aspiration samples.
AB  - BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration
      (EBUS-TBNA) is a minimally invasive modality with a high diagnostic yield for
      mediastinal lymph node staging of patients with lung cancer. Although limited to
      the use of needle aspiration during EBUS-TBNA, aspirates has been shown to be
      useful for molecular analysis. However, the ideal methodology of the specimen
      handling during EBUS-TBNA has not been described. METHODS: Based on our
      institutional experience and review of the literature, we describe the optimal
      methodology for multidirectional analysis of EBUS-TBNA samples. RESULTS: EBUS
      TBNA specimens can be used for molecular analysis such as epidermal growth factor
      receptor (EGFR), Anaplastic lymphoma kinase (ALK) and V-Ki-ras2 Kirsten rat
      sarcoma viral oncogene homolog (KRAS) mutations when processed properly. Rapid on
      site cytology is invaluable during the assessment of the aspirated during EBUS
      TBNA. DISCUSSION: Obtaining adequate samples through a non-surgical biopsy
      technique for pathologic diagnosis as well as molecular analysis will be of
      immediate importance for personalized management of lung cancer. EBUS-TBNA is an
      ideal approach that allows combined pathological and molecular analysis of
      metastatic lymph nodes.

PMID- 21178717
TI  - Bilateral subdural hematoma associated with central nervous system metastases
      from lung cancer.

PMID- 21178718
TI  - Small cell lung cancer in a 26-year-old man with significant Cannabis exposure.

PMID- 21178720
TI  - Best of the month: A round up of articles published in recent months.
AB  - With the abundant number of articles published in lung cancer, it has become very
      difficult to stay updated. After a search through variety of medical journal for
      articles published between March and June 2010, we selected the studies
      considered to have the greatest relevance for oncologists involved in the
      treatment of lung cancer. The nine selected studies covered a broad range of
      topics including possible hormonal role in the development of lung
      adenocarcinoma, lung cancer in never smokers, stereotactic radiotherapy for early
      stage lung cancer, prognostic role of pleural lavage cytology, neoadjuvant
      chemotherapy for operable lung cancer, maintenance erlotinib, use of erlotinib
      after gefitinib, comparison of the two epidermal growth factor receptor tyrosine
      kinase inhibitors, and risk of central nervous system relapse in patients treated
      with epidermal growth factor receptor tyrosine kinase inhibitors.

PMID- 21178719
TI  - KRAS mutation analysis helps to differentiate between pulmonary metastasis from
      colon adenocarcinoma in situ and primary lung adenocarcinoma.

PMID- 21178721
TI  - Summary of presentations from the 46th Annual Meeting of the American Society of
      Clinical Oncology: focus on non-small cell lung cancer (2010).
AB  - The promising results of crizotinib in molecularly selected patients with
      advanced non-small cell lung cancer (NSCLC) whose tumor cells had a novel fusion
      protein involving anaplastic lymphoma kinase presented at the 2010 American
      Society of Clinical Oncology reinforce once again the importance of understanding
      molecular heterogeneity of lung cancer and careful patient selection. Several
      other important issues were the subject of presentations related to lung cancer
      at the recently concluded American Society of Clinical Oncology annual meeting.
      The articles covered a wide variety of topics including optimal staging
      techniques to detect mediastinal nodal involvement, the role of platinum-based
      doublet chemotherapy in the management of elderly patients with advanced NSCLC,
      use of maintenance therapy with gemcitabine, and the impact of early introduction
      of organized palliative care in improving the quality of life of patients with
      advanced NSCLC. This report provides a brief overview of the presentations
      related to lung cancer that are relevant to clinical practice and future
      research.

PMID- 21178723
TI  - ERCC2/XPD polymorphisms and lung cancer risk.

PMID- 21178728
TI  - How new graduates can gain a competitive edge.

PMID- 21178729
TI  - Volunteers make the difference.

PMID- 21178730
TI  - Examining the role of the forensic nurse death investigator.

PMID- 21178731
TI  - Your guide to certification.
AB  - What you need to know to pursue professional recognition.

PMID- 21178732
TI  - Same-day surgery nursing: it takes teamwork.

PMID- 21178734
TI  - The Magnet(r) journey of a community hospital.

PMID- 21178735
TI  - Opportunity knocks for travel nurses.

PMID- 21178736
TI  - What's the state of interstate licensure?

PMID- 21178739
TI  - Implementing clinical systems with the future in mind.

PMID- 21178740
TI  - Improving the environment of care: what every nurse manager can do.

PMID- 21178741
TI  - Does journal club membership empower practice?

PMID- 21178742
TI  - Innovation in orientation: redesigning an RN residency program.

PMID- 21178743
TI  - 2010 Visionary leader.

PMID- 21178744
TI  - The makings of a Magnet(r) manager.

PMID- 21178746
TI  - Gender and professional values: a closer look.

PMID- 21178747
TI  - Learn, grow, and bloom by joining a professional association.

PMID- 21178748
TI  - Legally speaking...when can staff say no?

PMID- 21178749
TI  - The challenges and rewards of the cardiac universal bed model.

PMID- 21178750
TI  - Differentiating the CNS and CNL roles.

PMID- 21178751
TI  - Understanding ACOs, meaningful use.

PMID- 21178752
TI  - Carbon monoxide or nitric oxide: which came first?

PMID- 21178754
TI  - The impact of antiretroviral treatment on the burden of invasive pneumococcal
      disease in South African children: a time series analysis.
AB  - OBJECTIVE: HIV infection is a major risk factor for invasive pneumococcal disease
      (IPD). A national antiretroviral program was initiated in South Africa in 2004.
      This study evaluates the impact of the highly active antiretroviral therapy
      (HAART) treatment program on the burden of IPD among African children. DESIGN:
      Retrospective analysis of laboratory-confirmed IPD among children under 18 years
      of age, from 2003 to 2008. METHODS: The periods 2003-2004, 2005-2006 and 2007
      2008 were defined as the early, intermediate and established HAART eras,
      respectively. Pneumococcal conjugate vaccine was not introduced into public
      immunization during this period. RESULTS: One thousand, one hundred and seventy
      one episodes of IPD were identified over the study period. Among HIV-infected
      children under 18 years, the burden of IPD decreased by 50.8% [95% confidence
      interval (CI) 41.5-58.7] and the incidence of IPD-related mortality declined by
      65.2% (95% CI 47.2-77.0) from the early compared to the established HAART era.
      This decline in HIV-infected children was evident for pneumococcal bacteremia and
      pneumococcal meningitis. In addition, similar reductions were observed for
      serotypes included in a 7-valent pneumococcal conjugate vaccine and nonvaccine
      serotypes. The burden of IPD remained unchanged in HIV-uninfected children under
      18 years of age over these periods. The risk of IPD, however, remained 42-fold
      greater in HIV-infected compared to HIV-uninfected children in the established
      HAART era. CONCLUSIONS: Although the HAART program has been associated with
      significant declines in IPD morbidity and mortality, HIV-infected African
      children with access to HAART remain a high-risk group for IPD. These children
      should therefore be prioritized in the prevention of IPD.

PMID- 21178755
TI  - Use of lyophilized allogeneic costal cartilage: is it effective to maintain the
      projection of the reconstructed nipple?
AB  - The maintenance of adequate projection is one of the most important aspects in
      nipple reconstruction. A total of 17 nipples were reconstructed using the
      modified top hat flap technique with lyophilized allogeneic costal cartilage, and
      patients were followed up for 1 year. Projection at 6 months and 1 year was
      compared with the immediate postoperative result, as well as with the results of
      nipples reconstructed without cartilage. After 6 months and 1 year, there were
      significant reductions in projection, with the average losses of 51.7% and 57.7%,
      respectively. There were no significant differences between groups with or
      without cartilage. These findings show that nipples reconstructed with
      lyophilized allogeneic cartilage beneath the modified top hat flap showed no
      benefit compared with nipples reconstructed without cartilage.

PMID- 21178753
TI  - Vitamin D deficiency is associated with type 2 diabetes mellitus in HIV
      infection.
AB  - BACKGROUND: Metabolic complications, including type 2 diabetes mellitus and
      metabolic syndrome, are increasingly recognized among HIV-infected individuals.
      Low vitamin D levels increase the risk of type 2 diabetes mellitus, and vitamin D
      supplementation has been shown to decrease the risk of type 2 diabetes mellitus
      in patients without HIV infection. OBJECTIVES: The primary objective was to
      determine whether vitamin D deficiency (serum 25-hyrdoxyvitamin D <20 ng/ml) was
      associated with type 2 diabetes mellitus among HIV-infected patients. Our
      secondary objective was to determine whether vitamin D deficiency was associated
      with metabolic syndrome in HIV. METHODS: We conducted a cross-sectional study
      among participants enrolled in the prospective Modena (Italy) HIV Metabolic
      Clinic Cohort. Clinical and laboratory data, including history of type 2 diabetes
      mellitus, fasting blood glucose, components of metabolic syndrome, and 25
      hydroxyvitamin D levels, were obtained for all participants. RESULTS: After
      adjusting for vitamin D supplementation, sex, age, body mass index, and hepatitis
      C virus co-infection, vitamin D deficiency was associated with type 2 diabetes
      mellitus [adjusted odds ratio (OR) 1.85; 95% confidence interval (CI) 1.03-3.32;
      P = 0.038]. The association between vitamin D deficiency and metabolic syndrome
      was not significant after adjusting for vitamin D supplementation, sex, age and
      body mass index (adjusted OR 1.32; 95% CI 1.00-1.75; P = 0.053). CONCLUSIONS: Our
      study demonstrates an association between vitamin D deficiency and type 2
      diabetes mellitus. Clinical trials are needed to better characterize the
      association between vitamin D deficiency and type 2 diabetes mellitus in HIV
      infection and to evaluate whether vitamin D is able to prevent or delay the onset
      of type 2 diabetes mellitus.

PMID- 21178756
TI  - Subcutaneous pre-expansion of mastectomy flaps before breast reconstruction with
      deep inferior epigastric perforator flaps: eliminating the patch-like appearance
      and improving aesthetic outcomes.
AB  - INTRODUCTION: Free tissue transfer and tissue expansion are important tools in
      the reconstructive surgeon's armamentarium, yet are not often used in
      conjunction. Although tissue transfer has its advantages, the patch-like
      appearance of the skin paddle on the breast can be unappealing. OBJECTIVE: To
      present our clinical experience of using subcutaneous breast tissue expansion
      before reconstruction with deep inferior epigastric perforator (DIEP) flaps, and
      to show how this technique eliminates the patch-like appearance of the skin
      paddle. METHODS: Five patients underwent delayed breast reconstruction using a 3
      stage approach. During the first stage, tissue expanders were placed in the
      subcutaneous plane beneath the mastectomy flaps. After complete tissue expansion,
      the second stage involved removal of the tissue expanders and reconstruction of
      the breasts by burying deepithelialized DIEP flaps beneath the pre-expanded skin
      flaps. Revisions and nipple reconstructions were carried out in the third stage.
      Retrospective analysis of patients' characteristics, breast history, surgical
      stay, complications, and outcomes were performed. RESULTS: The patients were, on
      average, 49 years of age, with an average body mass index of 26.3. One patient
      underwent bilateral breast reconstruction whereas the rest had unilateral
      reconstructions. Two patients had minor complications. There were no DIEP
      failures or take-backs. CONCLUSION: Using subcutaneous breast tissue expansion
      followed by DIEP flap reconstruction can be performed safely, offering patients a
      completely autologous breast reconstruction with low morbidity, as well as
      eliminating the classical patch-like appearance of flap reconstructions.

PMID- 21178757
TI  - Index finger pollicization in the treatment of congenitally deficient thumb.
AB  - Congenital deficiency of the thumb greatly compromises hand function, because the
      normal thumb contributes at least 40% of its usefulness. The method of choice in
      the treatment of this functional liability is the pollicization of the index
      finger. This study presents the long term outcome of 21 index finger
      pollicizations in 18 patients, with a mean follow-up time of 9 years. The thumb
      deficiency was bilateral in 3 patients, whereas in 7 it was associated with
      radial club hand. The result was considered excellent in 75%, good in 19%, and
      poor in 6% of the 21 pollicizations, according to Percival's scoring system. The
      less rewarding function was obtained in the presence of associated radial club
      hand in combination with late reconstruction. Index finger pollicization is the
      method of choice in the treatment of thumb aplasia or severe hypoplasia. The
      younger patients adapt easier and use the new thumb in a more natural way.

PMID- 21178758
TI  - Free anterolateral thigh flap in pediatric patients.
AB  - The anterolateral thigh (ALT) flap represents a workhorse flap in reconstructive
      surgery. We describe our clinical experience with this flap in the pediatric
      population. A total of 20 patients with an average age of 9.5 years underwent a
      free ALT flap reconstruction. All flaps were commonly raised on 2 perforators.
      About 5 flaps were employed for head and neck reconstruction, 7 for upper and 8
      for lower limb reconstruction. Traumatic defects and congenital malformations
      represented the predominant etiology. Sizable perforators were found in all
      patients. The caliber was smaller compared to adults, and the course of the
      perforator was shorter. There were no complete flap losses and no significant
      donor-site morbidity. Donor-site closure required closure with split-thickness
      skin grafts in 6 cases. Hypertrophic scars developed in 4 patients. Secondary
      procedures included flap debulking (5) and Z-plasties (2). In conclusion,
      children have well-developed perforators supplying the ALT flap. With proper
      technique, this flap can be harvested and employed safely and reliably for
      reconstruction of varied defects in children.

PMID- 21178759
TI  - Reconstruction of large palatal defects using the free anterolateral thigh flap.
AB  - The ideal reconstructive method for the palatal defect should provide durable,
      stable coverage, and a natural contour, while simultaneously minimizing morbidity
      of both the defect and donor sites. Although small and usual palatal defects can
      be repaired easily using local adjacent tissues, successful closure of large,
      complex defects is still a challenging problem. Numerous free tissue options have
      to date been described for large palatal defects. Although the radial forearm
      flap constitutes a good option for ideal reconstructive goals, the sacrifice of a
      major artery to the hand and the skin graft to the forearm with its high
      potential risk of complications are evident problems attendant upon this donor
      site. Since the first report of the anterolateral thigh flap, this has become one
      of the most commonly used flaps for the reconstruction of various soft-tissue
      defects. Between April 2005 and May 2009, 8 free anterolateral thigh flaps were
      used to reconstruct defects of the palate. The study involved 6 male and 2 female
      patients, their ages ranging from 3 to 45. Five patients had palatal defects due
      to congenital cleft palate deformity, 2 patients had defects due to tumor
      resection, and the remaining patient had a palatal defect due to a gunshot wound.
      The size of the flaps ranged from 8 to 14 cm in length and from 4 to 7 cm in
      width. Facial vessels were used as recipient vascular sources in all patients.
      Primary thinning of the flap was performed in all cases. Donor sites were closed
      directly and healed uneventfully in all patients. There were no postoperative
      complications and all flaps survived totally. No debulking was needed. All
      patients, and their families in the case of child patients, were satisfied with
      the results of their surgical treatment. In conclusion, although it has some
      irregularity in derivation from the main vessels, with its evident structural and
      cosmetic advantages the anterolateral thigh flap can be considered an excellent
      and ideal free flap option for most large palatal defects that cannot be closed
      by regional tissue in selected patients. It can reconstruct defects in single
      stage with well-vascularized tissue, resulting in minimal donor site morbidity.

PMID- 21178760
TI  - Prehospital intravenous fluid administration is associated with higher mortality
      in trauma patients: a National Trauma Data Bank analysis.
AB  - OBJECTIVE: Prehospital intravenous (IV) fluid administration is common in trauma
      patients, although little evidence supports this practice. We hypothesized that
      trauma patients who received prehospital IV fluids have higher mortality than
      trauma patients who did not receive IV fluids in the prehospital setting.
      METHODS: We performed a retrospective cohort study of patients from the National
      Trauma Data Bank. Multiple logistic regression was used with mortality as the
      primary outcome measure. We compared patients with versus without prehospital IV
      fluid administration, using patient demographics, mechanism, physiologic and
      anatomic injury severity, and other prehospital procedures as covariates. Subset
      analysis was performed based on mechanism (blunt/penetrating), hypotension,
      immediate surgery, severe head injury, and injury severity score. RESULTS: A
      total of 776,734 patients were studied. Approximately half (49.3%) received
      prehospital IV. Overall mortality was 4.6%. Unadjusted mortality was
      significantly higher in patients receiving prehospital IV fluids (4.8% vs. 4.5%,
      P < 0.001). Multivariable analysis demonstrated that patients receiving IV fluids
      were significantly more likely to die (odds ratio [OR] 1.11, 95% confidence
      interval [CI] 1.05-1.17). The association was identified in nearly all subsets of
      trauma patients. It is especially marked in patients with penetrating mechanism
      (OR 1.25, 95% CI 1.08-1.45), hypotension (OR 1.44, 95% CI1.29-1.59), severe head
      injury (OR 1.34, 95% CI 1.17-1.54), and patients undergoing immediate surgery (OR
      1.35, 95% CI 1.22-1.50). CONCLUSIONS: The harm associated with prehospital IV
      fluid administration is significant for victims of trauma. The routine use of
      prehospital IV fluid administration for all trauma patients should be
      discouraged.

PMID- 21178761
TI  - Concomitant extrahepatic disease in patients with colorectal liver metastases:
      when is there a place for surgery?
AB  - OBJECTIVE: To evaluate the impact of the location of extrahepatic disease (EHD)
      on survival and to determine patient outcome in a consecutive series of patients
      with both intrahepatic and extrahepatic colorectal metastases treated by an
      oncosurgical approach, combining repeat surgery and chemotherapy. BACKGROUND:
      Although recognized as poor prognostic factor, concomitant EHD is no more
      considered an absolute contraindication to surgery in patients with colorectal
      liver metastases (CLM). However, the impact of the location of EHD on survival
      and the benefit in patient outcome is still diversely appreciated. METHODS: From
      840 patients resected for CLM between 1990 and 2006, 186(22%) also had resectable
      EHD. Sequential surgery was routinely combined with perioperative chemotherapy.
      Survival was compared with that of patients without EHD, prognostic factors were
      identified, and a predictive model was designed to better select surgical
      candidates. RESULTS: Patients resected for CLM with concomitant EHD experienced a
      lower 5-year survival than those without EHD (28% vs 55%, P < 0.001). Five poor
      prognostic factors were identified at multivariate analysis: EHD-location other
      than lung metastases (5-year survival: 23% vs 33%, P = 0.02), EHD concomitant to
      CLM recurrence (14% vs 34%, P < 0.001), carcinoembryonic antigen level at least
      10 ng/mL (16% vs 37%, P=0.02), at least 6 CLM(9% vs 32%, P = 0.02), and right
      colon cancer (P = 0.02). Five-year survival ranged from 64% (0 factors) to 0% (>3
      factors). In the EHD group, patients with an EHD-recurrence experienced better
      outcomes when resected than those treated by chemotherapy alone (5-year survival:
      38% vs 21%, P = 0.05). CONCLUSION: Although sequential surgery is warranted for
      patients with 5 or less CLM with isolated lung metastases, low carcinoembryonic
      antigen levels,and no right colon primary tumor, it should be questioned in the
      presence of more than 3 of these prognostic factors.

PMID- 21178764
TI  - Effects of chronic immunosuppression on long-term oncologic outcomes for
      colorectal cancer patients undergoing surgery.
AB  - INTRODUCTION: The effects of chronic immunosuppressive therapy (CIST) on long
      term oncologic outcomes for patients who undergo surgery for colorectal cancer
      are not known. We investigate whether CIST affects these outcomes. METHODS: From
      a prospective colorectal cancer database, patients undergoing colorectal
      resection for cancer between 1996 and 2005 and on CIST (steroids and/or
      cyclosporine, azathioprine, 6-mercaptopurine, FK-506, methotrexate) were
      identified and compared with a control group matched for age(+/-5 year), gender,
      type, and year (+/-2 year) of operation; American Society of Anesthesiology
      score; cancer stage; differentiation; vascular invasion; blood transfusion; and
      postoperative adjuvant therapy. The groups were compared for early and long-term
      outcomes. Cox models produced hazard ratios and Wald P values to assess
      associations between survival and the presence of immunosuppressive treatment.
      RESULTS: Fifty-five (20 female and 35 male) patients were on CIST for
      inflammatory disease, transplantation, chronic obstructive lung disease, other
      cancers, and hypopituitarism. Both groups were comparable for the matched
      characteristics. Chronic immunosuppressive therapy and control groups had similar
      overall postoperative morbidity (36.4% vs 27.3%, P = 0.3) and wound infection
      rates (14.5% vs 5.5%, P = 0.13). Chronic immunosuppressive therapy group had
      significantly lower 3- and 5-year overall (49.1% vs 76.3%, and 45.1% vs 66.2%,
      respectively, P = 0.003) and disease-free survival (45.5% vs 69.1%, and 41.7% vs
      63.3%, respectively, P = 0.005) than the control group. Local recurrence was
      similar between groups. CONCLUSION: Patients on chronic immunosuppression
      tolerate colorectal cancer resection but have significantly worse long-term
      oncologic outcomes.These findings need careful consideration when evaluating the
      relative roles of the various treatment modalities for this group of patients
      presenting with colorectal cancer.

PMID- 21178765
TI  - IGF system in cancer: from bench to clinic.
AB  - Insulin-like growth factors (IGFs) are important mediators of growth,
      development, and survival, and have been implicated in the pathogenesis of
      malignancies. The IGF system is a complex system comprising two growth factors
      (IGF-I and IGF-II), cell surface receptors (IGF-IR and IGF-IIR), six specific
      high-affinity binding proteins (IGFBP-1 to IGFBP-6), IGFBP proteases, and several
      other IGFBP-interacting molecules that regulate and propagate IGF actions in
      several tissues. IGFs are produced by almost any cell in the body; circulate in
      more than 1000-fold higher concentrations than most other peptide hormones, such
      as insulin, and their action is modulated by several binding proteins. Studies
      have revealed that IGFs may promote cell cycle progression and inhibition of
      apoptosis either by directly associating with other growth factors or indirectly
      by interacting with other molecular systems that have an established role in
      carcinogenesis and cancer promotion, such as steroid hormones and integrins. In
      addition, studies also suggest that increased serum levels of IGFs and/or altered
      levels of their binding proteins are associated with increased risk of developing
      cancers. These data underline the significance of IGFs system in the development
      of cancer risk, and a potential target for novel anticancer treatments and/or
      preventative strategies in high-risk groups. The researchers review the IGFs
      pathway and its implications in cancer development and treatment.

PMID- 21178766
TI  - New advances in molecular approaches to head and neck squamous cell carcinoma.
AB  - Head and neck squamous cell cancer is the sixth most common cancer in the world.
      Despite advances in combined modality therapy, poor outcomes continue to be
      observed in the form of locoregional recurrence, metastasis, and development of
      second primary tumors. As tumors vary in their molecular and genetic etiology and
      because often there is already deregulation at the molecular level in otherwise
      histopathologically normal tissue, risk stratification using clinical and
      pathologic criteria alone has proved to be inadequate. In this article, the
      reader will gain an appreciation for the current advances in biomarker discovery
      using advanced technology and data interpretation in microarray analysis and
      proteomics. In addition, other molecular targets, aside from epidermal growth
      factor receptor, are discussed in the context of their promising role in
      predicting recurrence, response to therapy, survival, and overall prognosis.

PMID- 21178767
TI  - Explaining gender differences in the white coat effect.
AB  - OBJECTIVES: To discern whether gender was a unique predictor of the white coat
      effect (WCE) in a population of normotensives and patients diagnosed with
      hypertension. METHODS: Participants (n=252) underwent a doctor's office visit to
      have their blood pressure measured. Multiple blood pressure readings were taken
      by both a research assistant and by the attending physician. In addition,
      measures of anxiety variables were collected during the visit. Participants then
      underwent a 36-h ambulatory blood pressure monitoring. RESULTS: Gender was a
      significant predictor of the systolic WCE, but, as expected, the effect size was
      small and was no longer significant when age and BMI were included in the
      regression model. State anxiety emerged as a significant independent predictor of
      systolic WCE; however, when household income was included in the model it became
      the only significant independent predictor (beta=0.203, P<0.05), in addition to
      gender, age, and BMI. CONCLUSION: This study suggests that the association
      between gender and the systolic WCE is small, and likely accounted for by other
      variables including age, BMI, state anxiety, and household income. Thus, gender
      may be of limited use in helping identify patients who may be more likely to have
      WCE or white coat hypertension. Gender differences in this area should be
      interpreted with great caution.

PMID- 21178768
TI  - The evaluation of the ability of closed-loop glycemic control device to maintain
      the blood glucose concentration in intensive care unit patients.
AB  - OBJECTIVES: Reduction in the variability of blood glucose concentration might be
      an important aspect of blood glucose management. A closed-loop glycemic control
      device (STG-22; NIKKISO, Tokyo, Japan) has been developed to maintain blood
      glucose levels within the target range through automatic infusion of insulin and
      glucose. We hypothesized that the STG-22 system could provide optimal blood
      glucose management without causing hypoglycemic events in patients admitted to
      intensive care units. In this study, we investigated the feasibility of glycemic
      control with the STG-22 system. Furthermore, we evaluated the variability in
      blood glucose concentration associated with the use of the STG-22 system. DESIGN:
      Retrospective analysis. SETTING: A five-bed medical/surgical intensive care unit
      in a university hospital. PATIENTS: Two hundred eight patients admitted to the
      intensive care unit between August 2006 and July 2009. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: We calculated the mean and sd of blood glucose
      concentrations in each patient during intensive insulin therapy (target range, 90
      110 mg/dL) administered using STG-22. In addition, to evaluate the blood glucose
      control achieved using STG-22, the durations for which the blood glucose level
      was maintained at 70-110 mg/dL, 110-150 mg/dL, 150-180 mg/dL, and>180 mg/dL were
      calculated. The average operation time of STG-22 was 33.9+/-42.4 hrs. The blood
      glucose level was maintained at 70-110 mg/dL for 49.5% of the study period; the
      corresponding values for 110-150 mg/dL, 150-180 mg/dL, and>180 mg/dL were 31.4%,
      7.0%, and 6.9%, respectively. No hypoglycemic events occurred. The sd of blood
      glucose levels was 19.9+/-10.9 mg/dL. After a level of 150 mg/dL was achieved,
      the sd of blood glucose was 12.6+/-3.1 mg/dL. CONCLUSIONS: STG-22 can help
      maintain optimal blood glucose levels without causing hypoglycemia in patients
      admitted to the intensive care unit. In addition, the use of this device might
      help decrease the variability in blood glucose concentration. Further randomized
      clinical trials are required to elucidate whether the low glucose variability
      maintained using STG-22 can contribute to improving the outcomes of patients
      admitted to the intensive care unit.

PMID- 21178769
TI  - Combining genome-wide data from humans and animal models of dyslipidemia and
      atherosclerosis.
AB  - PURPOSE OF REVIEW: Comparative genomics allows researchers to combine genome-wide
      association data from humans with studies in animal models in order to assist in
      the identification of the genes and the genetic variants that modify
      susceptibility to dyslipidemia and atherosclerosis. RECENT FINDINGS: Association
      and linkage studies in human and rodent species have been successful in
      identifying genetic loci associated with complex traits, but have been less
      robust in identifying and validating the responsible gene and/or genetic
      variants. Recent technological advancements have assisted in the development of
      comparative genomic approaches, which rely on the combination of human and rodent
      datasets and bioinformatics tools, followed by the narrowing of concordant loci
      and improved identification of candidate genes and genetic variants.
      Additionally, candidate genes and genetic variants identified by these methods
      have been further validated and functionally investigated in animal models, a
      process that is not feasible in humans. SUMMARY: Comparative genomic approaches
      have led to the identification and validation of several new genes, including a
      few not previously implicated, as modifiers of plasma lipid levels and
      atherosclerosis, yielding new insights into the biological mechanisms of these
      complex traits.

PMID- 21178771
TI  - Lipoprotein association studies: taking stock and moving forward.
AB  - PURPOSE OF REVIEW: Over the last year, huge progress has been made using SNP
      arrays to identify genes associated with lipid traits. RECENT FINDINGS: The
      single genome-wide association studies (GWASs) may have reached a limit in
      identifying novel genes, but there has been tremendous progress from
      collaborative consortia examining pooled data from GWASs, often employing SNP
      imputation. For example, the Global Lipid Consortium reported that 56 of the 95
      lipid-associated loci were novel to the pooled analysis from over 100 000
      individuals. Complementary to this, a gene-centric approach, such as the 50K IBC
      HumanCVD chip, which provides deep coverage of approximately 2100 genes, has had
      success in ascertaining independently acting variants and helped us to move a
      step closer to identify functional variants. Yet irrespective of the platform
      used, for each trait, the percentage variance explained by these genes remains in
      the order of approximately 10-12% and it is still unclear to what extent rare
      mutations, identified by resequencing or exome sequencing approaches, or gene *
      gene and gene * environment studies, might boost this. SUMMARY: GWAS-identified
      novel lipid-related loci highlight new pathways in lipid metabolism and may
      provide innovative drug targets. Furthermore, the use of lipid gene scores, over
      and above a single lipid measure, may have clinical utility.

PMID- 21178770
TI  - MicroRNAs in lipid metabolism.
AB  - PURPOSE OF REVIEW: Although the role for microRNAs (miRNAs) in regulating
      multiple physiological processes including apoptosis, cell differentiation, and
      cancer is well established, the importance of these tiny RNAs in regulating lipid
      metabolism has only recently been uncovered. This review summarizes the evidence
      for a critical role of miRNAs in regulating lipid metabolism. RECENT FINDINGS:
      Lipid metabolism is tightly regulated at the cellular level. In addition to
      classic transcriptional regulation of cholesterol metabolism (e.g. by SREBP and
      LXR), members of a class of noncoding RNAs termed miRNAs have now been identified
      to be potent post-transcriptional regulators of lipid metabolism genes involved
      in cholesterol homeostasis and fatty acid oxidation. Several reports have
      recently shown that miR-33 regulates cholesterol efflux and HDL biogenesis by
      downregulating the expression of the ABC transporters, ABCA1 and ABCG1. In
      addition, miR-33 also inhibits the translation of several transcripts encoding
      proteins involved in fatty acid beta-oxidation including CPT1a, CROT, and HADHB,
      thereby reducing fatty acid degradation. Other miRNAs including miR-122, miR-370,
      miR-335, and miR-378/378*, miR-27 and miR-125a-5p have been implicated in
      regulating cholesterol homeostasis, fatty acid metabolism and lipogenesis.
      SUMMARY: Recent advances in the understanding of the regulation of lipid
      metabolism indicate that miRNAs play major roles in regulating cholesterol and
      fatty acid metabolism. These new findings may open new avenues for the treatment
      of dyslipidemias.

PMID- 21178772
TI  - Contemporary clinical applications of spatio-temporal image correlation in
      prenatal diagnosis.
AB  - PURPOSE OF REVIEW: Four-dimensional fetal echocardiography has the potential to
      reduce the operator dependency of two-dimensional ultrasonography and increase
      the detection rate of congenital heart defects (CHDs). This review is intended to
      summarize recent evidence of the important role that four-dimensional
      ultrasonography with spatio-temporal image correlation (STIC) may play in the
      prenatal diagnosis of CHDs. RECENT FINDINGS: Four-dimensional ultrasonography
      with STIC may provide the opportunity for telemedicine in the prenatal diagnosis
      of CHDs because four-dimensional volume datasets can be remotely acquired and
      accurately interpreted by different centers. Four-dimensional ultrasonography
      with STIC is an accurate and reproducible technique for the prenatal diagnosis of
      CHDs. Different four-dimensional rendering techniques can provide important
      insight into the spatial relationships of normal and abnormal fetal vascular
      structures. SUMMARY: Four-dimensional fetal echocardiography with STIC may
      facilitate the examination of the fetal heart and could potentially increase the
      detection rate of CHDs.

PMID- 21178773
TI  - Gestational diabetes: evolving diagnostic criteria.
AB  - PURPOSE OF REVIEW: Gestational diabetes mellitus (GDM) is a common complication
      of pregnancy. There has been controversy and debate about how to optimally
      diagnose GDM and whether treatment modifies outcomes. We review the current
      controversies in both the screening and diagnosis of GDM and the benefits of
      treating GDM. RECENT FINDINGS: Three major studies have been published in the
      past 2 years that have evaluated these issues. The goal of the Hyperglycemia and
      Adverse Pregnancy Outcomes (HAPO) study was to determine the level of maternal
      glycemia at which adverse fetal/neonatal or maternal outcomes are impacted.
      Rather than a definitive cut-off, the study found that there was a continuous
      relationship between maternal glycemia and pregnancy outcomes. Two studies
      evaluated the effect of treating mild GDM on both maternal and neonatal outcomes.
      Each found a significant benefit with diagnosis and treatment. SUMMARY: Ideally,
      the results of the HAPO study will bring order to the current international
      confusion surrounding the diagnosis of GDM. Recently, the International
      Association of Diabetes and Pregnancy Study Groups recommended new screening
      criteria for GDM based on the HAPO study. Professional organizations around the
      world are currently considering these recommendations.

PMID- 21178774
TI  - Chronic hypertension in pregnancy.
AB  - PURPOSE OF REVIEW: Chronic hypertension is frequent in pregnant women as well.
      The objective of this review is to evaluate the maternal characteristics,
      pregnancy complications and birth outcomes including congenital abnormalities of
      pregnant women with chronic hypertension by reviewing the results of published
      studies and mainly the data of the population-based data set of the Hungarian
      Case-Control Surveillance System of Congenital Abnormalities. A second aim of the
      review is to examine the efficacy of antihypertensive drug treatments in the
      reduction of pregnancy-associated risks in women with chronic hypertension.
      RECENT FINDINGS: Pregnant women with treated chronic hypertension had a higher
      risk - beyond the well known pre-eclampsia and low birthweight newborns - of
      threatened abortion and preterm delivery, placental disorders and gestational
      diabetes. In addition a higher risk of hypospadias in one and of esophageal
      atresia/stenosis in another study was found in the children of pregnant women
      with chronic hypertension. These latter findings are signals which need
      confirmation or rejection in other studies. SUMMARY: The present antihypertensive
      treatments do not neutralize the harm of severe chronic hypertension in pregnant
      women and in their offspring, thus it is necessary to introduce more effective
      drug combinations for the treatment of pregnant women with severe chronic
      hypertension.

PMID- 21178775
TI  - Clinical implications of methicillin-resistant Staphylococcus aureus in
      pregnancy.
AB  - PURPOSE OF REVIEW: Methicillin-resistant Staphylococcus aureus (MRSA) has become
      an increasingly aggressive and prevalent pathogen in medicine. This pattern has
      also been noted in obstetrics. This review will delineate the epidemiology and
      clinical implications of MRSA during pregnancy. RECENT FINDINGS: Investigations
      have focused on prevalence of MRSA colonization in obstetrics and the associated
      morbidity. In addition, some attention has been focused on the neonatal
      implications of maternal colonization. Overall, the rates of maternal MRSA
      colonization noted in the United States have been low, in the range of 0.5-4%.
      The clinical impact of MRSA colonization among pregnant women has also been
      estimated to be modest. Roughly 357 invasive MRSA infections per 100,000 live
      births in the United States occur on an annual basis. It is however important to
      note that published estimates likely underestimate the full scope of MRSA in
      pregnancy given the lack of formal reporting, importance of related neonatal
      colonization and morbidity, the complicated treatment implications in pregnant
      women, the recognized high pathogenicity of MRSA infections, and propensity for
      recurrent infections among community-acquired MRSA strains. SUMMARY: MRSA is an
      increasingly important pathogen in modern healthcare and in the obstetric
      population. Continued surveillance and research remains a top priority.

PMID- 21178776
TI  - Risk factors in the aetiology of hiatus hernia: a meta-analysis.
AB  - OBJECTIVE: Hiatus hernia (HH) is commonly associated with gastro-oesophageal
      reflux disease, particularly reflux oesophagitis and Barrett's oesophagus. HH may
      increase with age as a result of fibromuscular degeneration. Obesity increases
      intra-abdominal pressure and may increase the risk of HH. A meta-analysis was
      undertaken to assess the influence of risk factors for HH. METHODS: Studies that
      included HH and potential aetiological factors (e.g. age, sex and BMI) as
      keywords were extracted from Medline. Studies and were required to define HH
      endoscopically and include unselected study populations. Data on a number of HH
      in relation to aetiological factors were extracted and a meta-analysis was
      performed, provided at least two suitable studies for each factor were available.
      RESULTS: From 2953 abstracts, 29 studies contained information on HH in relation
      to age, sex and BMI. Seven studies provided data for meta-analysis of the effect
      of age and HH was associated with age above 50 years [odds ratio 2.17, 95%
      confidence interval (CI): 1.35-3.51, P=0.001, I2=97.3]. Four studies provided
      data for meta-analysis of the effect of obesity and HH was associated with BMI
      above 25 kg/m2 (odds ratio 1.93, 95% CI: 1.10-3.39, P=0.002, I2=80.5). Eighteen
      studies provided data for meta-analysis of the effect of sex and HH was more
      common among men (odds ratio 1.36, 95% CI: 1.10-1.68, P=0.005, I2=89.5).
      Publication bias was assessed by the Classic fail-safe N test and no significant
      evidence of publication bias was noted. CONCLUSION: The prevalence of HH
      increases with age and increasing BMI and HH is more common among men.

PMID- 21178777
TI  - Reflux and irritable bowel syndrome are negative predictors of quality of life in
      coeliac disease and inflammatory bowel disease.
AB  - BACKGROUND AND AIM: An increased prevalence of reflux and irritable bowel
      syndrome (IBS) symptoms is associated with coeliac disease and inflammatory bowel
      disease (IBD). We aimed to determine the prevalence of reflux and IBS symptoms in
      a cohort of patients with coeliac disease and IBD and their relationship with
      quality of life (QoL) and psychological distress. METHODS: Histologically proven
      coeliac disease (n=225), ulcerative colitis (UC) (n=228), Crohn's disease (CD)
      (n=230) patients and age/sex-matched controls (n=348) completed the Short-Form 36
      (SF-36)-Item Health Survey, Hospital Anxiety and Depression Scale (HADS), reflux
      screen and Rome II criteria. RESULTS: UC patients report higher SF-36 (QoL)
      scores than coeliac disease; CD fairing worse overall (P<=0.0001). Reflux
      prevalence: coeliac disease 66%; UC 62%; CD 72%; controls 50%. Patients report
      reflux of a greater severity: coeliac disease odds ratio=6.8, 95% confidence
      interval=3.6-12.7, P<=0.001; IBD odds ratio=2.2, 95% confidence interval=1.6-3.2,
      P<=0.0001. Stepwise reductions in SF-36 scores in association with increasing
      reflux severity were found (P<=0.0001). IBS prevalence: coeliac disease 22%; UC
      16%; CD 24%; controls 6%. Concomitant IBS was associated with reduced SF-36
      scores in patients (P<=0.0001). CONCLUSION: Reflux and IBS are more prevalent in
      coeliac disease and IBD in comparison with age-matched and sex-matched controls.
      These additional symptoms are associated with reduced QoL and increasing
      likelihood of anxiety and depression. QoL may be improved if coeliac disease and
      IBD patients were assessed for reflux and IBS.

PMID- 21178778
TI  - Increased population prevalence of reflux and obesity in the United Kingdom
      compared with Sweden: a potential explanation for the difference in incidence of
      esophageal adenocarcinoma.
AB  - OBJECTIVES: The incidence of esophageal adenocarcinoma is five times higher in
      the UK than in Sweden. We examined the prevalence of established risk factors for
      esophageal adenocarcinoma in both populations. METHODS: A population-based cross
      sectional study comparing the prevalence of gastroesophageal reflux symptoms,
      obesity, and tobacco smoking between random samples of the English and Swedish
      populations aged 40-59 years. Data were collected through self-report
      questionnaires. Multivariable logistic regression yielded odds ratios with 95%
      confidence intervals, adjusting for potential confounding. RESULTS: The sample
      was composed of 3633 English and 1483 Swedish people (response rates 43 and 62%,
      respectively). The prevalence of reflux symptoms occurring at least weekly was
      twice as common in the English compared with the Swedish sample. Obesity (BMI
      >=30) was also nearly two-fold more common in the English sample. The frequency
      of tobacco smoking was similar in both countries. The combination of reflux
      symptoms and a BMI of at least 25 was three-fold more common in the English than
      in the Swedish sample. CONCLUSION: The substantially higher prevalence of reflux
      symptoms and obesity in samples of the English population compared with the
      Swedish population might contribute to the known higher incidence of esophageal
      adenocarcinoma in the UK.

PMID- 21178779
TI  - The impact of the metabolic syndrome--but not of hypertension--on all-cause
      mortality disappears in the elderly.
AB  - OBJECTIVE: The metabolic syndrome predicts the risk of cardiovascular and all
      cause death, but its clinical relevance in the elderly remains debatable. We
      aimed to determine the impact of the metabolic syndrome on all-cause mortality
      according to age, in comparison with hypertension alone. METHODS: We studied 129
      655 participants (82 110 men and 47 545 women) undergoing a standard health check
      up at the Investigations Preventives et Cliniques center (Paris, France). Mean
      follow-up was 4.9+/-2.6 years. The prevalence of the metabolic syndrome and its
      components was determined according to age group (<55, 55-65, >65 years old). All
      cause mortality according to metabolic syndrome and age was determined using Cox
      regression model analysis, unadjusted or adjusted for age, sex, smoking and other
      confounding factors. RESULTS: The prevalence of the metabolic syndrome and all
      its components except lipid parameters strongly increased with age. All-cause
      mortality associated with the metabolic syndrome (using three different
      definitions) was significantly elevated in participants below 55 years old, and
      was little affected by adjustment for confounding factors. However, it decreased
      from 1.77 (1.45-2.16) in participants below 55 years old to 1.12 (0.84-1.48) in
      participants above 65 years old [hazard ratio (95% confidence interval); National
      Cholesterol Education Program definition]. Waist circumference, fasting blood
      glucose and lipid parameters failed to predict mortality in participants above 65
      years old. In contrast, hypertension (blood pressure>140/90 mmHg or treatment)
      remained a significant predictor of all-cause mortality [hazard ratio 1.30 (95%
      confidence interval 1.02-1.66)] in participants above 65 years old. CONCLUSIONS:
      In a setting representative of primary care, hypertension but not the metabolic
      syndrome remains a strong risk factor for all-cause mortality in participants
      above 65 years old.

PMID- 21178763
TI  - Out-of-hospital hypertonic resuscitation after traumatic hypovolemic shock: a
      randomized, placebo controlled trial.
AB  - OBJECTIVE: To determine whether out-of-hospital administration of hypertonic
      fluids would improve survival after severe injury with hemorrhagic shock.
      BACKGROUND: Hypertonic fluids have potential benefit in the resuscitation of
      severely injured patients because of rapid restoration of tissue perfusion, with
      a smaller volume, and modulation of the inflammatory response, to reduce
      subsequent organ injury. METHODS: Multicenter, randomized, blinded clinical
      trial, May 2006 to August 2008, 114 emergency medical services agencies in North
      America within the Resuscitation Outcomes Consortium. INCLUSION CRITERIA: injured
      patients, age >= 15 years with hypovolemic shock (systolic blood pressure <= 70
      mm Hg or systolic blood pressure 71-90 mm Hg with heart rate >= 108 beats per
      minute). Initial resuscitation fluid, 250 mL of either 7.5% saline per 6% dextran
      70 (hypertonic saline/dextran, HSD), 7.5% saline (hypertonic saline, HS), or 0.9%
      saline (normal saline, NS) administered by out-of-hospital providers. Primary
      outcome was 28-day survival. On the recommendation of the data and safety
      monitoring board, the study was stopped early (23% of proposed sample size) for
      futility and potential safety concern. RESULTS:  : A total of 853 treated
      patients were enrolled, among whom 62% were with blunt trauma, 38% with
      penetrating. There was no difference in 28-day survival-HSD: 74.5% (0.1; 95%
      confidence interval [CI], -7.5 to 7.8); HS: 73.0% (-1.4; 95% CI, -8.7-6.0); and
      NS: 74.4%, P = 0.91. There was a higher mortality for the postrandomization
      subgroup of patients who did not receive blood transfusions in the first 24
      hours, who received hypertonic fluids compared to NS [28-day mortality-HSD: 10%
      (5.2; 95% CI, 0.4-10.1); HS: 12.2% (7.4; 95% CI, 2.5-12.2); and NS: 4.8%, P <
      0.01]. CONCLUSION: Among injured patients with hypovolemic shock, initial
      resuscitation fluid treatment with either HS or HSD compared with NS, did not
      result in superior 28-day survival. However, interpretation of these findings is
      limited by the early stopping of the trial. CLINICAL TRIAL REGISTRATION: Clinical
      Trials.gov, NCT00316017.

PMID- 21178780
TI  - Impact of malignant arterial hypertension on the heart.
AB  - OBJECTIVES: To assess the consequences of malignant hypertension and its
      evolution with antihypertensive treatment. BACKGROUND: Malignant hypertension can
      be considered as a model of the effects of very high blood pressure and renin
      angiotensin levels on target organs. However, the consequences on the heart have
      been little studied. METHODS: The consequences of malignant hypertension on left
      ventricular function and its evolution with treatment were assessed with
      echocardiography in a prospective study between January 2004 and June 2009.
      RESULTS: During the study period, 46 patients were referred to our unit for
      malignant hypertension of whom 25 could be included in the echocardiographic
      study. These patients showed at baseline important left-ventricular hypertrophy
      and alteration in systolic function. Global longitudinal strain was the most
      sensitive tool to assess impaired systolic function and was significantly reduced
      in 13 patients (<12.8, 52%). Short-term follow-up (1-3 months) showed a rapid
      improvement in systolic function together with significant hypertrophy
      regression. With a follow-up of 11 months on average all patients had recovered a
      normal global longitudinal strain with further but incomplete regression of
      hypertrophy. CONCLUSIONS: Our study highlights the significant impact of
      malignant hypertension on systolic function of the left ventricle, and the
      ability of this ventricle to quickly recover normal systolic function under
      antihypertensive treatment.

PMID- 21178781
TI  - Mid-trimester blood pressure drop in normal pregnancy: myth or reality?
AB  - BACKGROUND: Current dogma states that there is a mid-trimester fall in blood
      pressure (BP) in uncomplicated pregnancy. In the early stages of a longitudinal
      study of microcirculatory changes in pregnancy, we noted an absence of this mid
      trimester fall. METHOD: We prospectively studied this phenomenon in all our
      subsequent recruits. From a total of 326 women, 255 primigravid white women
      normotensive at booking and after delivery were studied. Serial BP measurements
      were taken under controlled conditions through to 38 weeks gestation. BP
      measurements by midwives were extracted from the case notes of 51 women within
      this cohort and analysed to validate the results. SBP progressively increased
      from the first trimester through to 38 weeks gestation. RESULTS: The increase
      from baseline at 13 weeks was significant when compared with measurements at 22
      weeks [mean difference: 2.8 mmHg; 95% (confidence interval) CI 1.9-3.7], 28 weeks
      (mean difference: 5.0 mmHg; 95% CI 3.5-6.5) and 36 weeks (mean difference: 7.7
      mmHg; 95% CI 6.2-9.1). DBP showed a nonsignificant dip at 22 weeks (mean
      difference: -0.12 mmHg; 95% CI -0.92 to 0.68), a nonsignificant increase at 28
      weeks (mean difference: 2.0 mmHg; 95% CI 0.80-3.2) and a significant increase at
      36 weeks (mean difference: 6.0; 95% CI 4.6-7.3). In the validation cohort, the
      SBP (P=0.0001) and DBP showed an increasing trend (P=0.0001). CONCLUSION: BP
      measured under controlled conditions showed a progressive rise in pregnancy, with
      no significant mid-trimester drop. The findings were replicated in the routine
      antenatal clinic measurements.

PMID- 21178782
TI  - Hypertension and sexual dysfunction: time to act.

PMID- 21178783
TI  - Serine/threonine kinase 39 is a candidate gene for primary hypertension
      especially in women: results from two cohort studies in Swedes.
AB  - BACKGROUND: As recently pinpointed by a genome-wide association study the
      serine/threonine kinase 39 (STK39) is a candidate gene for hypertension. This
      kinase is strongly implicated in sodium reabsorption by the kidney through its
      modulating effect on furosemide-sensitive and thiazide-sensitive channels. The
      aim of our study was to test the effects of the STK39 rs35929607A>G polymorphism
      on blood pressure (BP) levels and the prevalence and incidence of hypertension in
      middle-aged Swedes participating in two urban-based surveys in Malmo (Sweden).
      METHODS: The rs35929607A>G polymorphism was genotyped in 5634 participants
      included in the cardiovascular cohort of the 'Malmo Diet and Cancer
      cardiovascular arm' (MDC-CVA) study and successively in 17 894 participants of
      the 'Malmo Preventive Project' (MPP) both at baseline and at reinvestigation
      after a mean of 23 years. The effect of the same single nucleotide polymorphism
      on salt sensitivity was tested in 39 participants of the Salt Reduction to Avoid
      Hypertension study. RESULTS: Both before and after adjustment for covariates, the
      functional rs35929607A>G polymorphism was associated with higher SBP and DBP
      values in the MDC-CVA, but not in the MPP. In both surveys, the polymorphism was
      associated with hypertension prevalence; after adjustment using the autosomal
      dominant model, the odds ratio for hypertension ranged between 1.077 (MPP at
      baseline) and 1.151 (MDC-CVA) with P-value less than 0.05. After stratification
      for sex, the results remained statistically significant in women, but not in men.
      Carriers of the G-allele displayed an increase in salt sensitivity. CONCLUSION:
      Our results from two large cohort studies support previous evidence about the
      association of the STK39 rs35929607A>G variant with hypertension, especially in
      women. If further confirmed in successive studies, owing to its pivotal role in
      sodium reabsorption at the renal tubule level, STK39 might prove to be a suitable
      target for antihypertensive therapy. The greater effect of the STK39
      rs35929607A>G polymorphism in women with respect to men deserves further
      investigation.

PMID- 21178784
TI  - European Society of Hypertension Working Group on Obesity: obesity drugs and
      cardiovascular outcomes.

PMID- 21178785
TI  - Polymorphisms of antioxidant enzymes, blood pressure and risk of hypertension.
AB  - OBJECTIVE: To assess the association of single-nucleotide polymorphisms (SNPs) in
      genes codifying for antioxidant enzymes to blood pressure (BP) values and risk of
      hypertension. METHODS: Population-based study including 1388 participants (704
      women) older than 18 years in which 300 were untreated hypertensive patients. In
      335 untreated hypertensive patients referred to one hypertension clinic, the
      study was replicated. Thirty-five SNP throughout 13 genes were analyzed using
      SNPlex. In a subgroup of hypertensive patients, the amount of 8-oxo
      deoxyguanosine and GPX activity levels was measured in mononuclear cells.
      RESULTS: In the general population, genotypes with the G allele of the c.172G>A
      polymorphism in the SOD3 gene and those with the T allele of the c.-20C>T
      polymorphism in the CAT gene were associated with significant lower values of BP.
      Likewise, these genotypes were associated with less risk for hypertension after
      adjusting for confounder variables. Haplotypes in both genes increased the
      strength of associations. In the hypertensive patients, the same alleles of the
      two polymorphisms were associated with lower BP values too. In addition, two
      others, the CT-TT genotypes of the c.891C>T polymorphism in the GPX1 gene and the
      CT-CC genotypes of the c.-793T>C polymorphism of the TXN gene were also
      significantly associated to lower BP values. Furthermore, the CC genotype of the
      c.891C>T polymorphism in the GPX1 gene was associated with higher values of 8-oxo
      dG and GPX activity levels as compared to those for the CT-TT genotype.
      CONCLUSIONS: The results of the present study support the influence of
      antioxidant enzyme genes in BP values and hypertension risk.

PMID- 21178786
TI  - Chromogranin A: a novel factor acting at the cross road between the
      neuroendocrine and the cardiovascular systems.
AB  - Chromogranin A (CHGA) is a secretory protein stored in and released from neurons
      and cells of the diffuse neuroendocrine system. Cells of the adrenal medulla and
      adrenergic terminals are a main source of CHGA but also myocardial cells produce
      it under stress conditions. After secretion, CHGA is cleaved into several
      biologically active fragments, including vasostatins and catestatin. CHGA and its
      proteolytic peptides exert a broad spectrum of activities on the cardiovascular
      system. They act on blood pressure by controlling the vascular tone and the
      cardiac inotropic and chronotropic function. CHGA revealed to be a sensitive
      marker of myocardial dysfunction, with a high predictive power of morbidity and
      mortality in heart failure and ischemic heart disease. In addition, CHGA has been
      involved in the control of sustained endothelial inflammation and has been shown
      to be a good marker of persistent vascular inflammation in rheumatologic
      disorders affecting vessels.

PMID- 21178787
TI  - The effect of the bladder scanner policy on the number of urinary catheters
      inserted.
AB  - PURPOSE: The aim of this study was to determine if use of an ultrasonic bladder
      scanning device reduced the number of urinary catheters inserted in a medical
      surgical unit of an acute care facility. SUBJECTS AND SETTING: A stratified
      random sample of adult patients on a 28-bed medical-surgical unit at Northcrest
      Medical Center, located in Springfield Tennessee, was used for this study.
      METHODS: For 4 consecutive weeks data were collected from the medical records of
      adult patients on a medical-surgical inpatient care unit. All patients that were
      scanned based on the facility's policy were evaluated via retrospective chart
      review. The reasons for the bladder scan, results, and outcome were recorded.
      RESULTS: Seventy-nine scans were performed on 47 patients; 3 patients (4%)
      required straight (in and out) catheterization, and 8 (10%) required indwelling
      catheterization. Use of the bladder scanner allowed us to achieve an 80%
      reduction in catheterization among patients deemed "unable to void" based on
      clinical observation alone. Nearly 91% of individuals requiring urinary
      catheterization based on bladder scans were surgical patients; most were
      recovering from orthopedic procedures. CONCLUSION: Use of an ultrasonic bladder
      scanning device reduced the number of urinary catheters inserted and proved
      especially valuable when monitoring postoperative urinary retention in a medical
      surgical unit of an acute care facility.

PMID- 21178788
TI  - Factors affecting the healing of pressure ulcers in a Korean acute care hospital.
AB  - PURPOSE: We sought to determine the factors affecting pressure ulcer (PU) healing
      in an acute care facility in Korea. METHODS: Data were collected between October
      1, 2006, and September 30, 2007, regarding PU status and factors hypothesized to
      influence wound healing. INSTRUMENTS: We developed a form that queried factors
      thought to affect PU healing based on literature review. We also administered the
      Pressure Ulcer Scale for Healing (PUSH) tool to assess healing of PUs and
      calculated change in PUSH scale as the outcome variable reflecting the magnitude
      of the healing of PU. RESULTS: One hundred fifty eight patients with a total of
      326 PUs in an acute care hospital located in Seoul, Korea, comprised the sample.
      The variables found to significantly affect PU healing included mean arterial
      pressure (MAP), serum albumin level, urinary incontinence, consultation with
      nutritionist, Braden Scale scale, wound size, and exudate amount. Pressure ulcer
      healing was improved when the MAP was higher (B = 0.034) and the serum albumin
      level was more than 2.8 g/dL (20.8 grams/liter) (B = 1.107). CONCLUSION: When
      managing patients in an acute care setting, PU healing may be improved by
      maintaining MAP and providing protein supplements to keep serum albumin level
      greater than 2.8 g/dL (20.8 grams/liter).

PMID- 21178789
TI  - Changes in performance after implementation of a multifaceted electronic-health
      record-based quality improvement system.
AB  - BACKGROUND: Electronic health record (EHR) systems have the potential to
      revolutionize quality improvement (QI) methods by enhancing quality measurement
      and integrating multiple proven QI strategies. OBJECTIVES: To implement and
      evaluate a multifaceted QI intervention using EHR tools to improve quality
      measurement (including capture of contraindications and patient refusals), make
      point-of-care reminders more accurate, and provide more valid and responsive
      clinician feedback (including lists of patients not receiving essential
      medications) for 16 chronic disease and preventive service measures. DESIGN: Time
      series analysis at a large internal medicine practice using a commercial EHR.
      SUBJECTS: All adult patients eligible for each measure (range approximately 100
      7500). MEASURES: The proportion of eligible patients who satisfied each measure
      after removing those with exceptions from the denominator. RESULTS: During the
      year before the intervention, performance improved significantly for 8 measures.
      During the year after the intervention, performance improved significantly for 14
      measures. For 9 measures, the primary outcome improved more rapidly during the
      intervention year than during the previous year (P < 0.001 for 8 measures, P =
      0.02 for 1). Four other measures improved at rates that were not significantly
      different from the previous year. Improvements resulted from increases in
      patients receiving the service, documentation of exceptions, or a combination of
      both. For 5 drug-prescribing measures, more than half of physicians achieved 100%
      performance. CONCLUSIONS: Implementation of a multifaceted QI intervention using
      EHR tools to improve quality measurement and the accuracy and timeliness of
      clinician feedback improved performance and/or accelerated the rate of
      improvement for multiple measures simultaneously.

PMID- 21178791
TI  - Estimated risk of invasive breast cancer in postmenopausal women with and without
      family history of the disease.
AB  - OBJECTIVE: To characterize the estimated risk of invasive breast cancer (IBC) in
      postmenopausal women without a family history of breast cancer (FHBC), baseline
      risk scores were calculated using the Breast Cancer Risk Assessment tool. We also
      analyzed the incidence rates of IBC stratified by FHBC. METHODS: For the
      Continuing Outcomes Relevant to Evista (CORE) study population (n = 3,991;
      excluding women >=86 y of age or with a history of ductal carcinoma in situ or
      lobular carcinoma in situ), the prevalence of risk factors to the overall IBC
      risk was calculated. To evaluate IBC incidence rates, the placebo arm of the CORE
      trial (n = 1,275) was pooled with the placebo arm of the Raloxifene Use for the
      Heart trial (n = 5,047; total of 6,322 women). RESULTS: Common risk factors in
      the CORE population were age 65 years or older (78.4%) and menarche at 12 years
      or younger (29.4%). Incidence rates of IBC in the CORE plus Raloxifene Use for
      the Heart trial placebo populations correlated with IBC risk estimates; incidence
      rates were higher as risk scores increased. Of those who developed IBC, 65%
      (60/92) had scores between 1% and 2% and did not have FHBC; nearly half (43%;
      40/92) had risk scores below the high-risk cutoff of 1.66%. CONCLUSIONS: A
      significant portion of women who develop IBC do not have a family history of the
      disease. FHBC is important in assessing IBC risk; however, other relevant risk
      factors, together with FHBC and results from a validated tool risk assessment
      tool, should be jointly considered to develop a complete assessment of women's
      IBC risk.

PMID- 21178790
TI  - Circulating dehydroepiandrosterone sulfate levels in women who underwent
      bilateral salpingo-oophorectomy during the menopausal transition.
AB  - OBJECTIVE: A rise in circulating dehydroepiandrosterone sulfate (DHEAS)
      concentration occurs during the menopausal transition (MT) that is ovarian stage
      related but not age related. The objective of this study was to determine the
      source of the rise in circulating DHEAS. METHODS: Circulating DHEAS
      concentrations in women who had undergone bilateral salpingo-oophorectomy (BSO)
      were compared with the pattern of circulating DHEAS in women who progressed
      through the MT naturally. Annual serum samples from the Study of Women's Health
      Across the Nation (SWAN) over a 10-year study period were used. From 1,272 women
      in the SWAN cohort who were eligible for longitudinal evaluation of DHEAS annual
      samples, 81 underwent BSO during the premenopausal or early perimenopausal stage
      of the MT and were potentially available for study. Of these 81 BSO participants,
      20 had sufficient annual samples for evaluation of the post-BSO trajectory of
      circulating DHEAS. SWAN women not having used hormone therapy previously and
      those with intact ovaries were compared with women who underwent a BSO
      immediately after a premenopausal or early perimenopausal annual visit. There
      were no interventions, and circulating concentration of DHEAS was the main
      outcome. RESULTS: A detectable rise in DHEAS was observed in 14 (70%) of the 20
      BSO women, which is similar to the proportion (85%) of women with intact ovaries
      who had a detectable DHEAS rise. The mean rise in DHEAS (5%-8%) was similar in
      both BSO and non-BSO women. CONCLUSIONS: The MT rise in DHEAS (5%-8%) occurring
      in the absence of ovaries is largely of adrenal origin.

PMID- 21178792
TI  - Changes in serum antimullerian hormone levels across the ovulatory menstrual
      cycle in late reproductive age.
AB  - OBJECTIVE: The aim of this study was to assess the pattern of serum antimullerian
      hormone (AMH) across the normal ovulatory menstrual cycle in women in late
      reproductive age when ovarian follicle reserve and, hence, serum AMH levels are
      reduced. METHODS: Serum AMH levels were determined by enzyme-linked immunosorbent
      assay across the ovulatory menstrual cycle from women in mid (n = 18) and late (n
      = 43) reproductive life, including the menopausal transition. RESULT: : No
      intracycle variation in AMH level was observed in women in mid reproductive life
      nor in 33% (n = 14) of women with normal ovulatory cycles in late reproductive
      age. In the remaining cycles, a significant 2-fold decrease (P < 0.01) in AMH in
      11 cycles and a significant 4.2-fold increase (P < 0.01) in 10 cycles were
      observed between the follicular and luteal phases. In a further eight ovulatory
      cycles, AMH was below the level of assay detection. As ovarian follicle reserve
      decreases with age and AMH levels are reduced, separate patterns of AMH are
      detected in the follicular and luteal phases of ovulatory menstrual cycles,
      presumably reflecting the intermittent pattern of the emergence of follicles
      close to menopause. CONCLUSIONS: It is concluded that when AMH levels are
      substantially reduced, as in late reproductive age, they become less reliable as
      markers of ovarian reserve because of the changing patterns observed in some
      cycles.

PMID- 21178793
TI  - Osteocalcin as a marker of metabolic risk in healthy postmenopausal women.
AB  - OBJECTIVE: Several studies have reported the role of osteocalcin on glucose and
      fat metabolism. In this study, we analyzed the relationship between the
      concentration of osteocalcin and metabolic risk factors in healthy postmenopausal
      women. METHODS: Cross-sectional analyses of 54 postmenopausal women aged 56 +/-
      3.5 years were conducted. We recorded clinical and biochemical data of metabolic
      risk including fasting plasma glucose (FPG) level and evaluated the relationship
      between serum osteocalcin and bone formation markers. RESULTS: Serum osteocalcin
      concentration was negatively correlated with FPG (beta = -0.328, P = 0.035). When
      osteocalcin levels were divided into tertiles, we found significant differences
      in FPG between the highest and the lowest tertiles (84 +/- 11 vs 98 +/- 30 mg/dL,
      respectively; P = 0.029). We found significantly lower osteocalcin levels in
      women with impaired fasting glucose levels than in those with normoglycemia (10.7
      +/- 6.1 vs 17.1 +/- 7.4 ng/mL, respectively; P = 0.006). We also found lower
      concentrations of osteocalcin in obese women versus nonobese women (14.4 +/- 8.8
      vs 17.3 +/- 6.2 ng/mL; P = 0.034) and women with increased low-density
      lipoprotein cholesterol levels versus those with low LDL-c levels (14.1 +/- 5.4
      vs 18.9 +/- 9.1 ng/mL; P = 0.045). A concentration of 13.5 ng/ mL or lower showed
      a sensitivity of 85.7% and a specificity of 63.8% to detect increased risk for
      diabetes (FPG >=100 mg/dL). In contrast, serum levels of bone alkaline
      phosphatase did not correlate with any variable. CONCLUSIONS: In this population,
      there is a consistent association between osteocalcin and markers of metabolic
      syndrome. We suggest potential usefulness of serum osteocalcin as a predictor for
      increased risk of diabetes in postmenopausal women.

PMID- 21178794
TI  - Intralesional mitomycin-C for the treatment of conjunctival Kaposi sarcoma.
AB  - A 38-year-old human immunodeficiency virus-positive man presented with a
      progressively enlarging pigmented lesion in the right inferior fornix of the eye.
      A biopsy was performed of this lesion, which revealed Kaposi sarcoma.
      Intralesional mitomycin-C was delivered to the lesion, resulting in complete
      resolution of the sarcoma. At 36 months of follow-up, there is no evidence of
      recurrence. To the best of our knowledge, this is the first report of successful
      treatment of conjunctival Kaposi sarcoma with intralesional mitomycin-C.

PMID- 21178795
TI  - Dacryocystitis secondary to Stenotrophomonas maltophilia infection.
AB  - An 88-year-old man developed recurrent bouts of dacryocystitis and underwent
      dacryocystorhinostomy. Cultures from the lacrimal sac demonstrated
      Stenotrophomonas maltophilia. This uncommon bacterium is highly antibiotic
      resistant, and clinicians should consider it in atypical cases of infection and
      should guide antibiotic therapy appropriately.

PMID- 21178796
TI  - Topical antiglaucoma treatment with prostaglandin analogues may precipitate
      meibomian gland disease.
AB  - The popular use of topical prostaglandin analogues (TPAs) in glaucoma patients
      has a well-documented association with changes in number, length, thickness, and
      growth pattern of eyelashes. A link between meibomian gland disease and
      seborrheic blepharitis resulting from topical administration of prostaglandin
      analogues has not been made to the authors' knowledge. A retrospective study of
      43 patients presenting for incision and curettage of chalazion to the operating
      theatre over a 2-year period was performed. The patients' histories were reviewed
      to establish whether they were using TPAs for glaucoma at the time of surgery.
      Eight patients (19%) were using TPAs at the time of surgery. No patient had a
      history of eyelid margin disease before the commencement of TPAs. The exact
      pathogenesis of how meibomian gland disease is linked to TPA use is unclear. We
      postulate that the topical application of prostaglandin analogues may contribute
      to the formation of chalazion by acting directly to stimulate meibomian gland
      secretion. The authors present the findings of a preliminary case series showing
      a higher-than-expected incidence of patients using TPAs requiring surgical
      intervention for chalazion.

PMID- 21178797
TI  - Orbital roof encephalocele mimicking a destructive neoplasm.
AB  - The purpose of this case report is to report an orbital roof encephalocele
      mimicking a destructive orbital neoplasm. Orbital roof encephalocele is uncommon
      but can mimic neoplasm. One potential mechanism for the orbital roof destruction
      is a post-traumatic "growing orbital roof fracture." The growing fracture has
      been reported mostly in children but can occur in adults. Alternative potential
      etiologies for the encephalocele are discussed, including Gorham syndrome.
      Orbital roof encephalocele is uncommon in adults, and the findings can
      superficially resemble an orbital neoplasm. Radiographic and clinical features
      that might suggest the correct diagnosis include a prior history of trauma,
      overlying frontal lobe encephalomalacia without significant mass effect or edema,
      and an orbital roof defect. The "growing fracture" mechanism may be a potential
      explanation for the orbital roof destruction in some cases.

PMID- 21178798
TI  - Bifocal orbital and nasopharyngeal amyloidomas presenting as Graves disease.
AB  - A 72-year-old man presented with a slowly progressive left hyperglobus, left
      infraduction deficit, bilateral lower eyelid retraction, and dysphagia. He had a
      notable chin-down head position, diplopia in primary position, and 3 mm of left
      proptosis. He had been diagnosed with Graves disease 3 years before presentation.
      CT scans showed enlargement of the left inferior and medial rectus muscles with
      associated stranding of the retrobulbar fat and a low-density heterogeneous mass
      in the left aspect of the neck protruding in the nasopharynx. Biopsies of the
      orbit and nasopharynx revealed focal areas of amyloid. This represents the first
      report of bifocal amyloidomas of the orbit and nasopharynx.

PMID- 21178799
TI  - The use of soft tissue expanders in periocular reconstruction: a case series.
AB  - PURPOSE: To describe the use of soft tissue expanders for periocular
      reconstruction in the presence of limited local tissue availability. METHODS: A
      retrospective case series of 5 patients who attended the Manchester Royal Eye
      Hospital. They presented a reconstructive challenge due either to the presence of
      periocular scarring or to a marked loss or limitation of normal local skin for
      reconstruction. The soft tissue expander (SOE-3624 device) was inserted under the
      skin and subcutaneous tissue at a site selected to provide the desired additional
      tissue. Over periods of time varying from 6 to 16 weeks, the soft tissue expander
      was gradually inflated with injections of sterile saline in the outpatient
      clinic. As soon as the desired amount of additional skin and subcutaneous tissue
      had been obtained, reconstructive surgery was undertaken. Functional and cosmetic
      results were the main outcomes of the intervention. RESULTS: Four of the patients
      had the device inserted in the lower eyelid or cheek area and one patient had the
      device inserted above the eyebrow. No episode of tissue necrosis occurred in our
      patients. All the devices were tolerated by the patients and were removed without
      any complications. The implant migrated in one patient, limiting the
      reconstructive surgery, and one patient had a lateral canthal dehiscence
      following reconstruction. All patients thought that the surgery had improved
      their cosmesis. No patient required any additional surgical procedures.
      CONCLUSIONS: The authors conclude that the SOE-3624 tissue expander represents a
      good option in providing additional tissue for periocular reconstruction,
      particularly in younger patients. It was well tolerated and effective in this
      series.

PMID- 21178800
TI  - Re: "Radiographic analysis of extraocular muscle volumetric changes in thyroid
      related orbitopathy following orbital decompression".

PMID- 21178801
TI  - EGF and bFGF promote invasion that is modulated by PI3/Akt kinase and Erk in
      vestibular schwannoma.
AB  - OBJECTIVES: Vestibular schwannomas (VSs) are slow-growing benign tumors but, on
      rare occasion, can invade adjacent cranial nerves, causing significant morbidity,
      especially in association with neurofibromatosis 2 (NF2). We aimed to determine
      the role of the growth factors EGF, bFGF, and the hormone, Epo, in promoting such
      invasive behavior in VS, as well as their mechanisms of action. METHODS:
      Immunohistochemical staining showed expression of EGFR, bFGF, Epo, EpoR in
      archived VS tissue. Western blots and immunofluorescence showed expression of
      EGFR, EpoR and FGF in HEI-193, an immortalized cell line derived from human NF2
      related VS. Matrigel invasion assays were used to study the effect of Epo, FGF
      and bFGF on invasive behavior in HEI-193. Western blotting showed levels of
      phospho-Akt and phospho-Erk in HEI-193 upon addition of growth factors plus PI3K
      or MEK inhibitors. Quantitative RT-PCR was performed to determine the expression
      of MMP2 and MMP9 after treatment with growth factors. RESULTS: EGFR, bFGF, Epo
      and EpoR were expressed in VS tissue and HEI193. Addition of EGF and bFGF
      increased cellular invasion by 10 and 3.5-fold, respectively. Epo had minimal
      effect on invasion. Results indicated that Erk is involved in bFGF but not EGF
      induced invasion, while Akt is involved in both pathways. EGF treatment
      moderately induced MMP9, but is unlikely to account for the observed invasion.
      CONCLUSION: Activation of EGFR and FGFR may promote invasive behavior in VS
      through ERK and Akt signaling pathways. Further investigation will be necessary
      to elucidate their potential as useful targets in the treatment of VS.

PMID- 21178802
TI  - Speech development after cochlear implantation in children from bilingual homes.
AB  - OBJECTIVE: The aim of this study was to investigate whether exposure to a second
      language in bilingual families influences the spoken German skills after cochlear
      implantation. A further question was how many children with migration background
      are bilingual. STUDY DESIGN: Retrospective case review. SETTING: Tertiary
      referral center; cochlear implant program. PATIENTS: Ninety-three profoundly
      hearing-impaired children; 52 of these children reside in bilingual and 41 in
      monolingual homes. INTERVENTION: Cochlear implantation before the age of 6 years,
      speech and language skills assessments. MAIN OUTCOME MEASURES: Standard speech
      perception and receptive and expressive language measures. Data on used primary
      and secondary languages were obtained by questionnaire. RESULTS: Children growing
      up in bilingual homes performed worse than children from monolingual homes in all
      performed speech tests. Almost all children with bilingual parents indicated
      German as their main language. In some cases, the second language is used
      actively, but in most children, the use is limited to single words and
      expressions. However, some children from bilingual homes achieve high skill level
      in German language and, furthermore, develop competency in second spoken
      language. CONCLUSION: Advanced language skills including the learning of a second
      spoken language are possible for children with cochlear implant living in
      bilingual homes, but that is the exception rather than the rule. It seems that
      other factors, such as spoken German language skills of the parents, integration
      of the family, and compliance with the rehabilitation program, play an important
      role. Therefore, a special support for children with cochlear implants from
      bilingual homes is needed.

PMID- 21178803
TI  - Autoimmune inner ear disease in children.
AB  - OBJECTIVE: To determine the response to treatment of pediatric patients diagnosed
      with autoimmune inner ear disease. PATIENTS: Seven children who presented with
      sensorineural hearing loss and were diagnosed with autoimmune inner ear disease.
      INTERVENTION: Diagnosis through blood testing. Treatment with steroids and/or
      cytotoxic medication. MAIN OUTCOME MEASURES: Improvement in pure-tone average and
      speech discrimination scores on audiometric testing. RESULTS: Six of the 7
      children (85.7%) improved with treatment, and the remaining patient had no
      measurable progression of disease. CONCLUSION: Children with autoimmune inner ear
      disease seem to benefit from treatment with steroids and/or cytotoxic medication.
      Although such medications must be used with caution in the pediatric population,
      they should not be withheld simply because of young age.

PMID- 21178804
TI  - Predictive capability of historical data for diagnosis of dizziness.
AB  - OBJECTIVE: The study examines categorical responses to questions on a
      comprehensive dizziness questionnaire, to find the overall predictive power of
      the questionnaire, and to identify which question(s) are most predictive of each
      diagnosis. STUDY DESIGN: Retrospective chart review. SETTING: Specialized
      dizziness and balance center at a tertiary care hospital. PATIENTS: A total of
      619 patients (aged 19-89 yr, of whom 60% are women and 40% are men) diagnosed
      with 1 of 23 types of dizziness or postural instability. INTERVENTION: All
      patients were administered a standard 163-item dizziness questionnaire (including
      77 review of systems items). OUTCOME MEASURES: Predicted diagnoses from the
      questionnaire, as determined by binary and multinomial logistic regressions, are
      compared with an ultimate clinical diagnosis made by an expert neurotologist
      based on full interview, examination, and clinical tests. RESULTS: Significant
      question groupings exist for each of the main diagnoses. A subset of 47 questions
      under multinomial logistic regression gave high predictive accuracies for
      migraine (92%), benign paroxysmal positional vertigo (90%) and Meniere's disease
      (86%), and fair predictive power for vestibular neuritis (63%), contributing to
      an overall predictive accuracy of 84%. A smaller subset of 32 questions gave an
      overall predictive accuracy of 71%. CONCLUSION: The capability of historical data
      to accurately predict the ultimate diagnosis for dizziness emphasizes the
      importance of a structured questionnaire in the evaluation of such patients.
      Future developments include the formulation of a computer-based program to
      generate a differential diagnosis for the practitioner to consider.

PMID- 21178805
TI  - Radiologic study of a disposable drug delivery intracochlear catheter.
AB  - HYPOTHESIS: 1) To assess the insertion characteristics of a disposable
      intracochlear catheter; and 2) to assess radiologically cochlear trauma induced
      by delivery catheter and electrode arrays. BACKGROUND: A catheter was designed to
      enter the scala tympani up to 15 mm and to acutely deliver pharmacological agents
      during cochlear implantation. METHODS: A cadaveric study was conducted in
      accordance to national regulation. Thirteen fresh temporal bones were evaluated
      radiologically. The intracochlear catheter used in this experiment has the same
      outer dimensions and profile as a standard MED-EL cochlear implant electrode
      array. We performed sequentially the introduction of the catheter, the injection
      of an iodine solution into the scala tympani via the catheter, the removal of the
      catheter, and finally an electrode array insertion. Ten to 15 MUl of an iodine
      solution was injected into the scala tympani at depth of 15 mm. Four CT scans
      were sequentially performed after each step. RESULTS: The disposable
      intracochlear catheter could easily be inserted in all specimens. An insertion at
      depth of 15 mm was easily achieved every time. CT scans demonstrated that the
      iodine solution injected stayed in the scala tympani in all specimens. This was
      interpreted as indirect evidence of the integrity of the basilar membrane.
      CONCLUSION: Drug delivery during cochlear implantation using a flexible
      disposable intracochlear catheter has been demonstrated to be feasible and
      without radiological evidence of basilar membrane trauma to a distance of up to
      15 mm, as demonstrated in 13 temporal bones.

PMID- 21178806
TI  - Vestibular migraine: perspectives of otology versus neurology.
AB  - OBJECTIVE: To compare the attitudes and opinions of otologists and neurologists
      regarding the cause, diagnosis, and management of vestibular migraine. STUDY
      DESIGN: Survey questionnaire. METHODS: An 18-question survey designed to elicit
      opinions about the cause, diagnosis, pathophysiology, and management of migraine
      and dizziness was mailed to the entire memberships of the American Neurotology
      Society (ANS) and the International Headache Society (IHS). Survey participant
      responses were recorded for physician practice characteristics and for opinions
      on various clinical features of vestibular migraine. RESULTS: Of the 917 surveys
      mailed, 146 were completed by ANS members and 110 by IHS members. The frequency
      of respondents listing symptom origin as central to a diagnosis of migraine was
      43% for ANS members versus 62% of IHS members. Only 31% of ANS respondents
      thought that a sensory trigger was a major etiologic factor. Of the IHS
      respondents, 60% thought a triggering event was mediated by the Vth nerve and 28%
      by the VIIIth nerve. Opinions varied on the character of dizziness and cochlear
      symptoms associated with migraine. Compared with 26% of IHS members, 55% of ANS
      members were more likely to view hearing loss as a migraine symptom. IHS members
      expressed a greater tendency to use triptans and anticonvulsants when compared
      with ANS members. CONCLUSION: The results suggested that ANS and IHS members have
      different perspectives on the clinical presentation, pathophysiology, and
      management of vestibular migraine. These differences can result in patient
      confusion and inadvertently have an adverse effect on patient care, thereby
      potentially affecting patient outcomes.

PMID- 21178807
TI  - Revision aural atresia surgery: indications and outcomes.
AB  - OBJECTIVE: To determine the most common indications for revision congenital aural
      atresia (CAA) surgery and the postoperative healing and hearing outcomes of
      revision surgery. STUDY DESIGN: Retrospective case review. SETTING: Tertiary care
      academic otologic practice. PATIENTS: Patients undergoing revision surgery for
      CAA. INTERVENTION: Revision surgery for CAA. MAIN OUTCOME MEASURES: Indications
      for revision atresiaplasty, time to revision surgery, postoperative external
      auditory canal (EAC) patency, incidence of chronic drainage and/or infection, and
      postoperative speech reception thresholds (SRTs), and air-bone gaps. RESULTS:
      Indications for 75 ears (69 patients) undergoing 107 revision operations for CAA
      included 58% for EAC stenosis, 19% for chronic drainage and/or infection, and 20%
      for conductive hearing loss (CHL) alone. Fifty ears (67%) required a single
      revision. Twenty-five ears (33%) required more than 1 revision. With follow-up
      longer than 3 months (mean, 41 mo), 69% of ears revised for EAC stenosis achieved
      a patent canal (29% required >1 revision); 75% of ears revised for chronic
      drainage and/or infection (mean follow-up, 53 mo) realized a dry canal (22%
      required >1 revision). For all revision surgeries with adequate follow-up (n =
      80), the mean postoperative short-term SRT of 24 dB HL was a significant
      improvement from the mean preoperative SRT of 39 dB HL (p < 0.01, paired t test).
      CONCLUSION: EAC stenosis is the most common indication for revision
      atresiaplasty. Despite the challenges of revision surgery, improvement in canal
      patency, epithelialization, and hearing utcomes can be achieved.

PMID- 21178808
TI  - Otalgia associated with migraine.
AB  - OBJECTIVE: To investigate the association of otalgia and migraine. STUDY DESIGN:
      Retrospective survey with evaluation of otalgia response to migraine treatment.
      Only patients with minimum symptom duration of 3 months, who accepted migraine
      treatment and had a minimum follow-up of 3 months, were included. SETTING: Single
      neurotology practice. SUBJECTS: All patients with otalgia in whom other causes of
      otalgia had been excluded and who were treated with migraine therapies.
      INTERVENTION: Standard first-line abortive and prophylactic migraine therapies.
      MAIN OUTCOME MEASURES: Specific clinical data, as well as pretreatment and
      posttreatment severity scores, were gathered. Response to treatment was assessed
      by comparing pretreatment and posttreatment symptom scores using paired t test.
      RESULTS: A total of 26 patients were included. Ninety-two percent responded to
      migraine therapy with improved symptom frequency, severity, and duration (p <
      0.001). Median duration of symptoms was 5 years. Mean delay to response was 2.3
      weeks, and mean follow-up was 20 months. Otalgia was the chief complaint in 77%.
      Pain was dull in 35%, sharp in 19%, throbbing in 19%, and mixed in 27%. Sixty
      five percent demonstrated triggerability of otalgia. A total of 65% had
      International Headache Society migraine. Patients responded to many classes of
      migraine preventive and abortive medications. CONCLUSION: Otalgia of unclear
      cause can be related to migraine mechanisms. Our group showed a high prevalence
      of migraine characteristics, including headache, migraine-associated symptoms,
      patterns of triggerability, and response to migraine treatment. Clinical criteria
      for diagnosis of migraine-associated otalgia are suggested for future prospective
      study.

PMID- 21178809
TI  - Repetitive pediatric simulation resuscitation training.
AB  - OBJECTIVE: The objective of the study was to compare the effectiveness of
      repetitive pediatric simulation (RPS) training (scenario-debriefing-scenario) to
      standard pediatric simulation (STN) training (scenario-debriefing). METHODS:
      Pediatric and emergency medicine residents prospectively participated in
      simulated pediatric resuscitation training sessions in an in situ simulation
      room. Residents anonymously reported their knowledge, skills, and confidence
      after each session. Four learners and 2 faculty preceptors (1 pediatric emergency
      medicine attending physician and 1 pediatric emergency medicine fellow)
      participated in each session. Scenarios were performed on a high-fidelity
      simulator (SimBaby; Laerdal Medical, Stavanger, Norway), and video debriefing was
      used for all training sessions. Standard pediatric simulation was used in the
      initial 6 months of the study, whereas RPS was used in the second 6 months of the
      study. RESULTS: One hundred fifteen subjects completed simulation sessions during
      the study period. The RPS group reported higher overall debriefing quality and
      were more likely to report that the simulation session was an excellent method of
      teaching. The RPS group reported greater improvement in knowledge and skills than
      did the STN group. Similar scores were reported for confidence, overall
      performance, stress levels, and realism of the simulator in both the STN and RPS
      groups. CONCLUSIONS: Feedback is a key feature of effective medical simulation.
      Repetitive pediatric simulation provides learners with a discrete opportunity to
      apply the knowledge and skills discussed during debriefing in an immediate second
      simulation session and thereby complete Kolb's experiential learning cycle. In
      this study, the RPS debriefing format was associated with higher self-reported
      knowledge and skills. The RPS group reported more positive attitudes toward
      simulation than the STN group.

PMID- 21178810
TI  - Emergency department treatment failures for skin infections in the era of
      community-acquired methicillin-resistant Staphylococcus aureus.
AB  - BACKGROUND: Despite rapidly increasing incidence of skin and soft tissue
      infections (SSTIs) presenting to emergency departments (EDs), outcome data for
      these infections are limited. METHODS: This is a retrospective cohort study of
      children with culture-positive SSTI, managed as outpatients from a large
      pediatric ED in the year 2006. The primary outcome was treatment failure, defined
      as presence of 1 or more of the following: (1) change in antibiotic owing to poor
      clinical response, (2) subsequent incision and drainage, or (3) hospitalization.
      Demographics, isolated pathogens, and therapeutics were also assessed. To
      accurately capture the outcome of interest, only children who are observed in the
      hospital-based primary care network were included. RESULTS: Among 148 eligible
      subjects, there were 158 SSTIs including 131 abscesses, 19 folliculitis, and 8
      cellulitis. Mean age was 9.1 +/- 6.2 years, 41.2% were male, and 94.6% were
      African American. Methicillin-resistant Staphylococcus aureus (MRSA) was isolated
      in 66%, methicillin-sensitive S. aureus (MSSA) in 21%, and others in 13%. Outcome
      data were available for 144 subjects (97.2%). Emergency department treatment
      failure rate was 7.6% (95% confidence interval, 3.3%-12.0%); 10 of 11 failures
      were abscesses. Only S. aureus produced treatment failure and occurred in 13.3%
      of MSSA and 6.4% MRSA infections (odds ratio, 1.9; 95% CI, 0.5-7.1). An
      antibiotic to which the organism was sensitive was prescribed for 9 (81.8%) of 11
      treatment failures and did not differ between MRSA and MSSA; appropriate
      antibiotics were used in 91.5% of treatment successes. CONCLUSIONS: The rate of
      ED treatment failure for SSTI is low and is more likely to occur with S. aureus
      infection, irrespective of methicillin resistance or appropriate antibiotic
      therapy.

PMID- 21178811
TI  - Pain scores: are they used in sickle cell pain?
AB  - OBJECTIVES: We sought to evaluate the relationship between pain scores and time
      to analgesic administration in 2 patient groups: those with sickle cell disease
      (SCD) and those with long-bone fractures (LBFs). METHODS: Patients between the
      ages of 3 and 21 years who presented to a pediatric emergency department (ED)
      with a vaso-occlusive episode secondary to SCD or an isolated LBF during 2005
      were included. A retrospective chart review was conducted for each visit. Data
      collected included demographics, visual analog scale (VAS) pain scores, and time
      analgesic intervention. In 2005, all patients with SCD received analgesic
      management according to protocol. RESULTS: Seventy-seven patients with SCD had
      152 visits to the ED for pain, whereas 219 patients had 221 visits for isolated
      LBF. In the long-bone-fracture group, for every 1-point increase in the VAS
      score, time to analgesic administration decreased by 5.6 minutes (P = 0.003),
      whereas in the SCD group, there was no relationship between VAS score and time to
      analgesic administration (P = 0.69). CONCLUSIONS: Our data suggest that pain
      scores are not used in the initial decision-making process in those patients with
      SCD presenting to the ED; however, they are utilized for patients presenting with
      another painful condition.

PMID- 21178812
TI  - Pediatric emergency department-based rapid HIV testing: adolescent attitudes and
      preferences.
AB  - OBJECTIVE: The objective of this study was to describe adolescent
      attitudes/preferences toward rapid HIV testing in a pediatric emergency
      department (PED). METHODS: An anonymous survey was completed by adolescents who
      presented to an urban PED. The survey was completed while they participated in a
      rapid HIV prevention/testing program. Survey questions included demographics, HIV
      risk factors/knowledge, prior testing experience, and attitudes/preferences
      toward rapid HIV testing. RESULTS: One hundred fourteen adolescents between the
      ages of 14 and 21 years were surveyed. Most respondents (69%) reported that the
      emergency department was a very high preference location for testing. Eighty
      percent of adolescents agreed that they were more likely to get tested for HIV if
      a rapid test was available. Most participants strongly agreed that it was
      important to receive pretest and posttest counseling for HIV. In addition, 38%
      strongly agreed that they preferred a same-sex counselor, whereas 9% strongly
      agreed that they preferred a same-ethnicity counselor. Eighty-one percent
      reported that they planned to get retested for HIV in the next 6 to 12 months.
      CONCLUSIONS: This study offers valuable new insights into adolescent attitudes
      and preferences for rapid HIV testing in a PED. Adolescents gave high ratings to
      the location, testing, and counseling process. Our data support the importance of
      structured counseling, which is contrary to current published perspectives of
      counseling efficacy. In addition, we found that the PED was a highly preferred
      location for rapid HIV testing, which supports the need for increased development
      of prevention and testing programs in this setting.

PMID- 21178813
TI  - Sichuan earthquake and emergency relief care for children: report from the
      firstly arrived pediatricians in the epicenter zone.
AB  - OBJECTIVE: An 8.0-magnitude earthquake struck Sichuan province of China on May
      12, 2008. Over the next 10 days, the firstly arrived uniformed pediatricians in
      the epicenter zone took part in emergency relief care for children. The
      investigations of major injuries and diseases in children were taken. METHODS:
      Demographic data collected included (if possible) age, date of presentation,
      injury, disease, and surgery performed. RESULTS: Total casualties were estimated
      to be more than 80,000, and much more were injured. Eight hundred eighty-two
      inpatients were treated by the relief team during the first 10 days. Of 882
      inpatients, 192 (21.8%) were younger than 18 years. Children's ages were not
      evenly distributed. Twenty-seven patients were neonates, infants, and toddlers
      (14%), 105 were school-aged (55%), and were 60 adolescents (31%). The admitted
      children had 256 injuries. Limb (106 cases, 55.2%) and body surface (67 cases,
      34.9%) were the majorly injured locations. One hundred twenty-seven cases (66.2%)
      had simple open injuries, and 106 (55.2% had fractures. The children's conditions
      were evaluated as mild (121 cases, 63.0%), moderate (56 cases, 29.7%), severe (8
      cases, 4.2%), and fatal (7 cases, 3.7%). CONCLUSIONS: More than 20% of patients
      requiring hospitalization were children. School-aged children were heavily
      injured. The increase in infectious diseases followed on. The data show that
      there is an immediate need for orthopedic and general surgery skills, and
      pediatricians should play an important role in early rescue and subsequent
      control of infectious diseases in a huge earthquake hazard.

PMID- 21178814
TI  - Efficacy of a near-infrared light device in pediatric intravenous cannulation: a
      randomized controlled trial.
AB  - OBJECTIVES: To determine whether the use of a near-infrared light venipuncture
      aid (VeinViewer; Luminetx Corporation, Memphis, Tenn) would improve the rate of
      successful first-attempt placement of intravenous (IV) catheters in a high-volume
      pediatric emergency department (ED). METHODS: Patients younger than 20 years with
      standard clinical indications for IV access were randomized to have IV placement
      by ED nurses (in 3 groups stratified by 5-year blocks of nursing experience)
      using traditional methods (standard group) or with the aid of the near-infrared
      light source (device group). If a vein could not be cannulated after 3 attempts,
      patients crossed over from one study arm to the other, and study nurses attempted
      placement with the alternative technique. The primary end point was first-attempt
      success rate for IV catheter placement. After completion of patient enrollment, a
      questionnaire was completed by study nurses as a qualitative assessment of the
      device. RESULTS: A total of 123 patients (median age, 3 years) were included in
      the study: 62 in the standard group and 61 in the device group. There was no
      significant difference in first-attempt success rate between the standard (79.0%,
      95% confidence interval [CI], 66.8%-88.3%) and device (72.1%, 95% CI, 59.2%
      82.9%) groups. Of the 19 study nurses, 14 completed the questionnaire of whom 70%
      expressed neutral or unfavorable assessments of the device in nondehydrated
      patients without chronic underlying medical conditions and 90% found the device a
      helpful tool for patients in whom IV access was difficult. CONCLUSIONS: First
      attempt success rate for IV placement was nonsignificantly higher without than
      with the assistance of a near-infrared light device in a high-volume pediatric
      ED. Nurses placing IVs did report several benefits to use of the device with
      specific patient groups, and future research should be conducted to demonstrate
      the role of the device in these patients.

PMID- 21178815
TI  - Risk factors for contamination of catheterized urine specimens in febrile
      children.
AB  - BACKGROUND: Urinary tract infections are the most common serious bacterial
      infection in febrile infants. Bladder catheterization is the preferred method of
      obtaining urine for culture in young children. Contamination of urine can be
      recognized when nonpathogens or multiple pathogens are isolated; preliminary
      culture results may lead to unnecessary antibiotics pending final identification.
      Some low-colony count (<50,000 colony-forming units per milliliter) cultures may
      represent contamination or asymptomatic bacteriuria. OBJECTIVE: Identify clinical
      factors that lead to contamination of catheterized urine specimens. METHODS:
      Physicians and nurses in an urban pediatric emergency department completed a
      survey after performing bladder catheterization of febrile children 36 months or
      younger. Contamination was defined by multiple pathogens, nonpathogens, or colony
      counts less than 10,000 colony-forming units per milliliter. RESULTS: : One
      hundred eighty-five children were studied. The median age was 8.4 months
      (interquartile range, 2.4-14.4 months). Sixty-eight percent were girls. Forty-six
      percent of boys were circumcised. Of the 185 children, 18 (10%) had true UTI.
      Fourteen percent of cultures were contaminated. Univariate analysis of potential
      predictors identified age younger than 6 months (odds ratio [OR], 6.8; 95%
      confidence interval [CI], 2.6-17.9), difficult catheterization (OR, 3.6; 95% CI,
      1.5-8.6), and uncircumcised boys (OR, 5.7; 95% CI, 1.2-29.4). The contamination
      rate in uncircumcised boys younger than 6 months was 43% (95% CI, 26-66). Volume
      of urine, sex, and catheter size were not predictive of contamination.
      CONCLUSIONS: Children younger than 6 months and uncircumcised boys are at
      increased risk of contaminated specimens from bladder catheterization. Suprapubic
      aspiration or use of a fresh, sterile catheter with each repeated attempt at
      catheterization may lead to less contamination in these patients.

PMID- 21178816
TI  - Effects of neonatal stress and morphine on murine hippocampal gene expression.
AB  - Critically ill preterm infants experience multiple stressors while hospitalized.
      Morphine is commonly prescribed to ameliorate their pain and stress. We
      hypothesized that neonatal stress will have a dose-dependent effect on
      hippocampal gene expression, and these effects will be altered by morphine
      treatment. Male C57BL/6 mice were exposed to five treatment conditions between
      postnatal d 5 and 9: 1) control, 2) mild stress + saline, 3) mild stress +
      morphine, 4) severe stress + saline, and 5) severe stress + morphine. Hippocampal
      RNA was extracted and analyzed using Affymetrix Mouse Gene 1.0 ST Arrays. Single
      gene analysis and gene set analysis were used to compare groups with validation
      by qPCR. Stress resulted in enrichment of gene sets related to fear response,
      oxygen carrying capacity, and NMDA receptor synthesis. Morphine down-regulated
      gene sets related to immune function. Stress + morphine resulted in enrichment of
      mitochondrial electron transport gene sets and down-regulation of gene sets
      related to brain development and growth. We conclude that neonatal stress alone
      influences hippocampal gene expression, and morphine alters a subset of stress
      related changes in gene expression and influences other gene sets. Stress +
      morphine show interaction effects not present with either stimulus alone. These
      changes may alter neurodevelopment.

PMID- 21178817
TI  - Relationships between renin, aldosterone, and 24-hour ambulatory blood pressure
      in obese adolescents.
AB  - Renin-angiotensin system (RAS) activation and abnormalities of ambulatory blood
      pressure (ABP) are present in obesity, but relationships between components of
      the RAS and ABP have not been defined in the young. Anthropometric measurements
      and 24-h ABP were obtained on 30 obese adolescents with and without type 2
      diabetes mellitus. Plasma renin activity (PRA), aldosterone, and other
      cardiovascular risk factors were measured. Median PRA levels were 2.5
      [interquartile range (IQR), 1.7-4.1] ng/mL/h and were higher in the diabetic
      subjects compared with the nondiabetics. Females had significantly higher PRA
      than males 3.2 (IQR, 2-4.8) versus 1.8 (IQR, 1.1-2.9) ng/mL/h (p = 0.04) and were
      more obese. BMI Z score and PRA were significantly correlated (rho = 0.46, p <
      0.001). PRA inversely correlated with 24-h systolic ABP (rho = -0.46, p = 0.02)
      and strongly with 24-h pulse pressure (rho = -0.61, p = 0.001). Aldosterone
      levels were also correlated with 24-h pulse pressure (rho = -0.46, p = 0.02). In
      multivariate models, lower PRA was independently associated with 24-h systolic
      blood pressure. In this study, PRA was positively correlated with BMI, but the
      relationships between components of the RAS and ABP were inverse. Further studies
      are needed to define the pathophysiologic relationship between RAS components and
      blood pressure regulation in obese youth.

PMID- 21178818
TI  - Developmental stage is a major determinant of lung injury in a murine model of
      bronchopulmonary dysplasia.
AB  - Bronchopulmonary dysplasia (BPD) is a common inflammatory lung disease in
      premature infants. To study the hypothesis that the sensitivity of the lung to
      inflammatory injury depends on the developmental stage, we studied postnatal lung
      development in transgenic mice expressing human IL-1beta (hIL-1beta) in the lungs
      during the late canalicular-early saccular, saccular, or late saccular-alveolar
      stage. Overexpression of hIL-1beta in the saccular stage caused arrest in
      alveolar development, airway remodeling, and goblet cell hyperplasia in the lungs
      as well as poor growth and survival of infant mice. Overexpression of hIL-1beta
      during the late canalicular-early saccular stage did not adversely affect lung
      development, growth, or survival of the pups. Mice expressing hIL-1beta from the
      late saccular to alveolar stage had smaller alveolar chord length, thinner septal
      walls, less airway remodeling and mucus metaplasia, and better survival than mice
      expressing hIL-1beta during the saccular stage. Human IL-1beta overexpression in
      the saccular stage was sufficient to cause a BPD-like illness in infant mice,
      whereas the lung was more resistant to hIL-1beta-induced injury at earlier and
      later developmental stages.

PMID- 21178819
TI  - Patients with Rett syndrome sustain low-energy fractures.
AB  - We present the first case-control study addressing both fracture occurrence and
      fracture mechanisms in Rett syndrome (RTT). Two previous studies have shown
      increased fracture risk in RTT. This was also our hypothesis regarding the Danish
      RTT population. Therefore, we investigated risk factors associated with low
      energy trauma and the association to methyl-CpG-binding protein 2 (MECP2)
      mutations. A total of 61 female patients with RTT and 122 healthy controls
      matched according to age and pubertal/menopause status were examined by
      questionnaires, bone biochemical markers in blood, and clinical and x-ray
      evaluations. National register search on fracture diagnoses was done to obtain
      complete fracture histories. Our results showed that patients with RTT sustained
      significantly more low-energy fractures from early age compared with controls,
      even though overall fracture occurrence apparently was not increased. Low-energy
      fractures were significantly associated with less mobility and lack of
      ambulation. Associations with MECP2 mutations or epilepsy were not demonstrated,
      contrary to previous findings. Blood biochemistry indicated a possible need for D
      vitamin supplementation in RTT. Our study casts light on fracture occurrence in
      RTT and points to a need for future research in bone development and fracture
      risk to establish directions for improved prevention and treatment of low-energy
      fractures in RTT.

PMID- 21178820
TI  - Contribution of sarcoplasmic reticulum Ca2+ release and Ca2+ transporters on
      sarcolemmal channels to Ca2+ transient in fetal mouse heart.
AB  - Sarcoplasmic reticulum (SR) Ca release has been shown not to be the predominant
      mechanism responsible for excitation-contraction (E-C) coupling in fetal
      myocytes. However, most of the studies have been conducted either on primary
      cultures or acutely isolated cells, in which an apparent reduction of ryanodine
      receptor density have been reported. We aimed to elucidate the contribution of SR
      Ca release and Ca transporters on sarcolemmal channels to Ca transients in fetal
      mouse whole hearts. On embryonic day 13.5, ryanodine significantly reduced the
      amplitude of the Ca transient to 27.2 +/- 4.4% of the control, and both nickel
      and SEA0400 significantly prolonged the time to peak from 84 +/- 2 ms to 140 +/-
      5 ms and 129 +/- 6 ms, respectively, whereas nifedipine did not alter it.
      Therefore, at early fetal stages, SR Ca release should be an important component
      of E-C coupling, and T-type Ca channel and reverse mode sodium-calcium exchanger
      (NCX)-mediated SR Ca release could be the predominant contributors. Using
      embryonic mouse cultured cardiomyocytes, we showed that both nifedipine and
      nickel inhibited the ability of NCX to extrude Ca from the cytosol. From these
      results, we propose a novel idea concerning E-C coupling in immature heart.

PMID- 21178821
TI  - Tetrahydrobiopterin is present in high quantity in human milk and has a
      vasorelaxing effect on newborn rat mesenteric arteries.
AB  - Breast milk reduces the incidence of necrotizing enterocolitis (NEC). BH4 is a
      cofactor for endothelial NOS (eNOS). Reduced BH4 levels, or its oxidation to
      dihydrobiopterin (BH2), uncouple eNOS resulting in formation of reactive oxygen
      species (ROS) that have been implicated in the pathogenesis of NEC. We evaluated
      colostrum and mature breast milk, as well as infant formula, BH4 and BH2 content.
      In addition, we tested the BH4 effect on the newborn rat mesenteric arterial
      vascular tone. BH4 and BH2 content increased 3-fold in mature breast milk, when
      compared with colostrum (p < 0.01), without a change in their ratio. Infant
      formula had a negligible BH4 content and lower biopterins ratio, when compared
      with breast milk. eNOS is the predominant synthase isoform in newborn rat
      mesenteric arteries. In the presence of BH4, mesenteric arteries contracted less
      to thromboxane A2 analog U46619 (p < 0.01) and this effect was abolished
      following eNOS inhibition. BH4 (10-6 M) vasorelaxed the newborn rat mesenteric
      arteries. We conclude that when compared with infant formula, breast milk has a
      high BH4 content that increases as breastfeeding continues. Given its mesenteric
      arterial vasorelaxing effect, BH4 may play an important role in the reduced NEC
      incidence among breast fed infants.

PMID- 21178822
TI  - High positive end-expiratory pressure during high-frequency jet ventilation
      improves oxygenation and ventilation in preterm lambs.
AB  - Increasing positive end-expiratory pressure (PEEP) is advocated to recruit
      alveoli during high-frequency jet ventilation (HFJV), but its effect on
      cardiopulmonary physiology and lung injury is poorly documented. We hypothesized
      that high PEEP would recruit alveoli and reduce lung injury but compromise
      pulmonary blood flow (PBF). Preterm lambs of anesthetized ewes were instrumented,
      intubated, and delivered by cesarean section after instillation of surfactant.
      HFJV was commenced with a PEEP of 5 cm H2O. Lambs were allocated randomly at
      delivery to remain on constant PEEP (PEEPconst, n = 6) or to recruitment via
      stepwise adjustments in PEEP (PEEPadj, n = 6) to 12 cm H2O then back to 8 cm H2O
      over the initial 60 min. PBF was measured continuously while ventilatory
      parameters and arterial blood gases were measured at intervals. At postmortem, in
      situ pressure-volume deflation curves were recorded, and bronchoalveolar lavage
      fluid and lung tissue were obtained to assess inflammation. PEEPadj lambs had
      lower pressure amplitude, fractional inspired oxygen concentration, oxygenation
      index, and PBF and more compliant lungs. Inflammatory markers were lower in the
      PEEPadj group. Adjusted PEEP during HFJV improves oxygenation and lung compliance
      and reduces ventilator requirements despite reducing pulmonary perfusion.

PMID- 21178823
TI  - Rate of phenylalanine hydroxylation in healthy school-aged children.
AB  - Hydroxylation of phenylalanine to tyrosine is the first and rate-limiting step in
      phenylalanine catabolism. Currently, there are data on the rate of phenylalanine
      hydroxylation in infants and adults but not in healthy children. Thus, the aim of
      the study reported here was to measure the rate of phenylalanine hydroxylation
      and oxidation in healthy school-aged children both when receiving diets with and
      without tyrosine. In addition, hydroxylation rates calculated from the isotopic
      enrichments of amino acids in plasma and in very LDL apoB-100 were compared.
      Eight healthy 6- to 10-y-old children were studied while receiving a control and
      again while receiving a tyrosine-free diet. Phenylalanine flux, hydroxylation,
      and oxidation were determined by a standard tracer protocol using oral
      administration of 13C-phenylalanine and 2H2-tyrosine for 6 h. Phenylalanine
      hydroxylation rate of children fed a diet devoid of tyrosine was greater than
      that of children fed a diet containing tyrosine (40.25 +/- 5.48 versus 29.55 +/-
      5.35 MUmol . kg-1 . h-1; p < 0.01). Phenylalanine oxidation was not different
      from phenylalanine hydroxylation regardless of dietary tyrosine intake,
      suggesting that phenylalanine converted to tyrosine was mainly oxidized. In
      conclusion, healthy children are capable of converting phenylalanine to tyrosine,
      but the need for tyrosine cannot be met by providing extra phenylalanine.

PMID- 21178824
TI  - Acute kidney injury reduces survival in very low birth weight infants.
AB  - Acute kidney injury (AKI) independently predicts mortality in children and
      adults. Our understanding of the epidemiology of AKI in very LBW (VLBW) infants
      is limited to retrospective studies. After adjustment for demographics,
      comorbidities, and interventions, infants with AKI have decreased survival
      compared with those without AKI. The study was conducted in regional quaternary
      care NICU of the University of Alabama at Birmingham. VLBW infants were followed
      prospectively and were classified into a serum creatinine (SCr)-based
      classification for AKI. Forty-one of 229 (18%) VLBW infants developed AKI. Those
      with AKI were more likely to have umbilical artery catheters, assisted
      ventilation, blood pressure medications, and lower 1-and 5-min Apgar scores. Of
      the infants with AKI, 17 of 41 (42%) died compared with 9 of 188 (5%) of those
      without AKI (p < 0.001). AKI was associated with mortality with a crude hazard
      ratio (HR) of 9.3 (95% CI, 4.1-21.0). After adjusting for potential confounders,
      those with AKI had higher chance of death as the adjusted HR was 2.4 (95% CI 0.95
      6.04). AKI is associated with mortality in VLBW infants. Efforts to prevent and
      ameliorate the impact of AKI may improve the outcomes in this vulnerable
      population.

PMID- 21178825
TI  - Bone mineral content and density in Rett syndrome and their contributing factors.
AB  - This study used densitometry to investigate the areal bone mineral density (aBMD)
      and bone mineral content (BMC) in an Australian Rett syndrome cohort and to
      assess how factors such as genotype, epilepsy, BMI, and mobility affect these
      parameters. The influence of lean tissue mass (LTM) and bone area (BA) on total
      body BMC (TBBMC) was also investigated. Participants, recruited from the
      Australian Rett Syndrome Database (ARSD), had TBBMC and lumbar spine (LS) and
      femoral neck (FN) aBMD measured using Dual energy x-ray absorptiometry. Mean
      height standardized Z scores and CIs for the bone outcomes were obtained from
      multiple regression models. The mean height Z score for the FN aBMD was low at 
      2.20, while the LS aBMD was -0.72. The TBBMC mean height Z score was -0.62,
      although once adjusted for BA and LTM, the mean was above zero, suggesting that
      low BMC can be explained by narrow bones and decreased muscle mass, likely
      secondary to decreased mobility. Multiple linear regression identified the
      p.R168* and p.T158M mutations as the strongest predictors of low aBMC and BMD for
      all bone outcomes. The strong relationship between genotype, BMC, and aBMD is
      likely underpinned by the strong relationship between LTM, mobility, and bone
      outcome measures.

PMID- 21178826
TI  - Linkage and association study of neurotrophins and their receptors as novel
      susceptibility genes for childhood IgA nephropathy.
AB  - Neurotrophins (NTs) and their receptors (NTRs) are known to be important for
      pathogenesis of various inflammatory diseases that occur in not only neuronal but
      also nonneuronal tissues, including kidney. Here, we investigated association
      between childhood IgA nephropathy (IgAN) and single nucleotide polymorphisms
      (SNPs) of genes encoding NTs [nerve growth factor (NGF) and brain-derived
      neurotrophic factor (BDNF)] and NTRs [nerve growth factor receptor (NGFR) and
      neurotrophic tyrosine kinase receptor 1-3 (NTRK1-3)]. The genotyping data of 197
      patients and 289 control subjects revealed significant association between NGF
      SNP rs11102930 and presence of IgAN. Patient subgroup analysis revealed that that
      the presence of nephrotic range proteinuria (>40 mg/m/h) was associated with
      rs6334 of NTRK1 and rs11030104, rs7103411, rs7103873, and rs6484320 of BDNF.
      Significant genotype differences were observed in podocyte foot process
      effacement for rs1187321 and rs1187323 of NTRK2. Furthermore, some SNPs showed
      significantly different genotype distribution between patients with or without
      pathologically advanced disease markers, specifically in rs6334 of NTRK1. Our
      results suggest that SNPs of NTs and NTRs are associated with susceptibility,
      pathological advancement, podocyte foot process effacement, and development of
      proteinuria in childhood IgAN.

PMID- 21178827
TI  - Adipogenic gene variants in patients with HIV-associated lipodystrophy.
AB  - OBJECTIVES: Although highly active antiretroviral therapy (HAART) has been hugely
      beneficial in the treatment of HIV, HIV lipodystrophy (HIVLD) associated with
      HAART is a serious adverse effect, with long-term consequences including
      metabolic disturbances and an increased risk of atherosclerotic disease. Although
      HIVLD is clearly related to the drug regimen, individual susceptibility also
      plays a role. We hypothesized that variation in genes regulating adipogenesis,
      and in those implicated in inherited forms of lipodystrophy, may predispose to
      the development of HIVLD. METHODS: DNA samples were obtained from 180 HAART
      treatedHIV+ patients: 124 with HIVLD (HIVLD+) and 56 without HIVLD (HIVLD-).
      Diagnosis of HIVLD was carried out by clinician's confirmation of patient self
      report. High-throughput genotyping using Sequenom was used to screen 62 single
      nucleotide polymorphisms (SNPs) in eight genes involved in adipogenesis and
      inherited forms of lipodystrophy. Statistical analysis was performed using
      Haploview. Multivariate analysis (logistic regression) was used to identify
      independent predictors of HIVLD development in HAART-treated patients. RESULTS:
      SNPs in two adipogenesis regulators, LPIN1 and CEBPalpha, showed a significant
      association with HIVLD whereas a SNP in ZMPSTE24, a zinc metalloproteinase
      involved in prelamin A processing, showed a trend toward significance.
      Multivariate analysis identified time since HIV diagnosis (P=0.001) and carriage
      of more than one associated allele (P=0.008) to be the most significant
      independent predictors for the development of HIVLD. CONCLUSION: Genetic
      variation in key regulators of adipogenesis could interfere with fat storage and
      metabolism contributing to the development of HIVLD in HAART-treated HIV
      patients. These results need replication in other cohorts.

PMID- 21178828
TI  - Apoptosis in the sequestrated nucleus pulposus compared to the remaining nucleus
      pulposus in the same patient.
AB  - STUDY DESIGN: Both sequestrated nucleus pulposus (SNP) and the remaining nucleus
      pulposus (RNP) were studied from the discs of the same patient to evaluate
      apoptosis using immunohistochemical staining. OBJECTIVE: To compare apoptosis of
      the SNP and the RNP in the disc of the same patient. SUMMARY OF BACKGROUND DATA:
      Many studies have been conducted on the natural history and apoptosis of the
      herniated nucleus pulposus; however, apoptosis of the remaining nucleus cells,
      after removal of the sequestrated disc, in the same patient, has not been
      reported. MATERIALS AND METHODS: Eight samples of SNP and RNP from the disc of
      the same patient were obtained. The TUNEL stain was performed to confirm the
      occurrence of apoptosis in disc cells. Immunohistochemistry staining and Western
      blot analysis were performed to determine the presence of proteins, including
      caspase-3,-8,-9, and Bid. RESULTS: TUNEL-positive chondrocytes were identified in
      all of the SNP and RNP samples; the apoptotic index was 5.8 +/- 1.9% and 5.9 +/-
      1.2%, respectively (P = 0.60). Caspase-3,-8,-9, and Bid were expressed in the SNP
      and the RNP of the cytoplasm and the nucleus by the immunohistochemical staining.
      The expression of active caspase-3,-8,-9, and Bid in the RNP of the disc and the
      SNP was different in each patient. CONCLUSION: The frequency of chondrocyte
      apoptosis in the SNP and the RNP was not different in the disc. The pathways
      involved in chondrocyte apoptosis of the SNP and the RNP differed among
      individuals and included intrinsic and/or extrinsic pathways.

PMID- 21178829
TI  - Mechanical patterns of cervical injury influence postoperative neurological
      outcome: a verification of the allen system.
AB  - STUDY DESIGN: Retrospective clinical case study. OBJECTIVE: To evaluate whether
      spinal column injury severity influences neurological outcome after cervical
      spine injury patterns of Allen's classification. SUMMARY OF BACKGROUND DATA:
      Allen's classification is commonly used in cervical fracture/dislocation.
      Cervical spine injuries are classified into 6 common patterns by their mechanism.
      Each pattern is divided into stages according to spinal column damage severity,
      and these stages have been closely correlated with the neurological damage at
      injury. However, the validity of the relationship has not been adequately
      discussed. Moreover, only a few reports have assessed whether the injury pattern
      influences the neurological outcome. METHODS: We selected 155 patients with
      unstable subaxial cervical spine injuries. Only 146 patients having more than 12
      month postoperative follow-up were included. All were treated with posterior
      spinal arthrodesis. Supplemental anterior surgery was added in four patients. The
      injury patterns were graded using Allen's classification. The neurological status
      at injury and final follow-up was evaluated using the American Spinal Injury
      Association (ASIA) impairment scale. RESULTS: Patients were categorized by using
      Allen's classification as follows: distractive flexion, 82; compressive flexion,
      29; compressive extension, 21; vertical compression, 8; and distractive
      extension, 6. In distractive flexion cases, the ratios of ASIA A cases at final
      follow-up increased with advancing stage (27%, 18%, 63%, and 100% in stages 1-4;
      P < 0.001). Furthermore, in similar cases with neurological deficit, the ratio of
      postoperative improvement on the ASIA impairment scale (>1 level) decreased with
      advancing stage (62%, 67%, 27%, and 0% in stages 1-4; P < 0.01). With other
      patterns, neurological outcome was likely to be influenced by spinal column
      injury severity. CONCLUSION: Injury patterns based on Allen's classification well
      correlated with the neurological outcome and recovery rate. This was especially
      evident distractive flexion cases. Thus, Allen's classification can be a
      predictor of neurological outcome after cervical spine injury.

PMID- 21178830
TI  - Effect of number of fusion levels on S1 screws in long fusion construct in a calf
      spine model.
AB  - STUDY DESIGN: In vitro biomechanical study evaluating the effect of fusion levels
      on simulated S1 screws on calf spines. OBJECTIVE: To measure the stresses of
      simulated S1 screws as a function of increasing fusion levels in long-fusion
      construct. SUMMARY OF BACKGROUND DATA: Extension of long fusion to sacrum remains
      a difficult clinical challenge despite the recent knowledge and technology.
      Several biomechanical studies have evaluated the bending moment on sacral screw
      of various fixation techniques. The high risk of sacral screw failure has been
      primarily attributed to the long lever arm of instrumentation and pullout force
      on S1 screw. However, none of these studies characterized how the number of
      fusion levels affected the sacral screw stresses. Because the number of fusion
      levels is an important factor in considering additional fixation options to
      protect the sacral screws, the effect of fusion levels on sacral screw stresses
      must be understood. METHODS: Eight calf spines (T13-L5) were used in this study
      (L5 is simulated as S1). Twelve pedicle screws were inserted. A combination of
      strain gages were attached to the spinal rods located between L4 and L5. Pure
      flexion moment (7.5 Nm) was applied to the partially fused construct as the level
      of fusion varied between 1 and 5 levels. The number of fusion levels increased
      from lower vertebrae to upper vertebrae. The pullout force, bending moment, and
      transverse force acting on the S1 screw were calculated from the strain gage
      signals. One way repeated measure ANOVA was used to analyze the pullout force,
      bending moment, and transverse force data. RESULTS: The pullout force and
      transverse load had significant difference between single and multilevel fusion.
      However, no difference was found among multilevel fusion procedures (all P >
      0.05). The mean pullout force was 29 +/- 8 and mean transverse force was 139 +/-
      18 N. For bending moment, there was no statistical difference among all fusion
      levels. The average bending moment was 1.02 +/- 0.34. Addition of anterior
      interbody cages at lower levels (L3-L4 and L4-L5) reduced the stresses on the
      simulated S1 screw by approximately 20% with P < 0.05. CONCLUSION: All three
      stresses, flexion moment, transverse load, and screw pullout force, must be
      considered in studying the biomechanics of long-fusion construct. There was no
      significant increase in sacral screw loading with increasing fusion levels when
      the same flexion moment was applied. It is postulated that the higher load
      present in long-fusion construct may lead to the premature failure of the
      lumbosacral fixation.

PMID- 21178831
TI  - Prospective analysis of imaging prediction of pseudarthrosis after anterior
      cervical discectomy and fusion: computed tomography versus flexion-extension
      motion analysis with intraoperative correlation.
AB  - STUDY DESIGN: A prospective comparison of quantitative motion analyzed (QMA)
      flexion/extension radiographs versus computed tomography (CT) as an analytical
      predictor of cervical pseudarthrosis. Intraoperative confirmation of the fusion
      was performed. OBJECTIVE: To prospectively compare motion analyzed
      flexion/extension radiographs to CT to predict pseudarthroses. Define motion
      thresholds on flexion/extension radiographs to define pseudarthroses. SUMMARY OF
      BACKGROUND DATA: Assessment of postoperative fusion success is an important
      factor in assessing success after anterior cervical spine fusion. Gross
      intervertebral motion can be used as a measure; however, the current "gold
      standard" for determining fusion status is a CT to assess bridging bone. Defining
      the amount of intervertebral motion at the fusion site has been previously
      addressed and definitions have varied widely. METHODS: Data were analyzed at 47
      fusion segments. Intervertebral motion at the fusion site was measured from
      flexion/extension radiographs taken at least 1 year after the cervical spine
      fusion. Motion was quantified from digitized radiographs by an independent
      researcher using proprietary quantitative motion analysis (QMA) software. CT
      scans on all patients were analyzed for fusion status by a neuroradiologist.
      Those patients determined to have a symptomatic pseudarthrosis were revised and
      intraoperative motion at the facet joints was documented. Correlation between
      intraoperative findings, CT and QMA was performed. RESULTS: Using greater than 4
      degrees  of measured motion on flexion/extension radiographs resulted in a
      Spearman correlation P-value of 0.096 (95% confidence interval: -0.06 to 0.66).
      Using greater than 1 degrees  of motion, the Spearman correlation P < 0.0001 (95%
      CI: 0.54-0.90). The positive predictive value (PPV) using 4 degrees  of motion as
      the criterion was 100%, indicating a high specificity. The negative predictive
      value (NPV) was 52%, indicating a low sensitivity. Using greater than 1 degrees 
      of motion, the PPV was 100% and the NPV was 73%. Findings from CT showed an
      identical PPV and NPV to assessments made using greater than 1 degrees  of
      rotation. Specificity and positive predictive value were 100% for all criteria.
      Using a lack of bridging on CT or more than 1 degrees  of intervertebral motion
      during flexion/extension increased the sensitivity to 85% and the negative
      predictive value to 85%. CONCLUSION: A threshold level of 4 degrees  of motion is
      commonly used to identify a pseudarthrosis. Our prospective study suggests that
      this value has a high PPV, but a low specificity and would miss many of the
      pseudarthroses that have angular motion less than 4 degrees  (sensitivity 23%).
      By lowering the threshold for angular motion to 1 degrees , the sensitivity
      improves to 77%. CT scan has been touted as the gold standard, and it has a high
      positive predictive value of 100%. However, its NPV was slightly lower than using
      1 degrees  of motion on QMA analyzed flexion-extension films (73% vs. 79%). In
      conclusion, although CT scan has long been regarded as the gold standard for
      determining a pseudarthrosis in the cervical spine, the interpretation is
      subjective and vulnerable to both type I and type II errors. Analysis of motion
      using Quantitative Motion Analysis is seemingly less subjective than CT and in
      our prospective study was more predictive of an operatively confirmed
      pseudarthrosis.

PMID- 21178833
TI  - Evidence and Impact: Should these articles Change the Practice of Spine Care? An
      Evidence Based Medicine Process.

PMID- 21178832
TI  - Qigong versus exercise versus no therapy for patients with chronic neck pain: a
      randomized controlled trial.
AB  - STUDY DESIGN: Randomized controlled trial. OBJECTIVE: To evaluate whether qigong
      is more effective than no treatment and not inferior to exercise therapy. SUMMARY
      OF BACKGROUND DATA: Lifetime prevalence of chronic neck pain is close to 50%.
      Qigong is often used by patients, although, the evidence is still unclear.
      METHODS: Patients (aged 20-60 years) with chronic neck pain (visual analog scale,
      VAS >= 40 mm) were randomized to 1) qigong or 2) exercise therapy (18 sessions
      over 6 months) or 3) waiting list (no treatment). At baseline and after 3 and 6
      months, patients completed standardized questionnaires assessing neck pain (VAS),
      neck pain and disability, and quality of life (Short Form SF-36 questionnaire, SF
      36). The primary endpoint was average pain in the last 7 days on VAS at 6-month
      follow-up. Statistical analysis included generalized estimation equation models
      adjusted for baseline values and patient expectation. RESULTS: A total of 123
      patients (aged 46 +/- 11 years, 88% women) suffering from chronic neck pain for
      3.2 (SD +/- 1.6) years were included. After 6 months, a significant difference
      was seen between the qigong and waiting list control groups (VAS mean difference:
      -14 mm [95%CI = -23.1 to -5.4], P = 0.002). Mean improvements in the exercise
      group were comparable to those in the qigong group (difference between groups 
      0.7 mm [CI = -9.1 to 7.7]) but failed to show statistical significance (P =
      0.092). Neck pain and disability, and SF-36 results also yielded superiority of
      qigong over no treatment and similar results in the qigong and exercise therapy
      groups. CONCLUSION: Qigong was more effective than no treatment in patients with
      chronic neck pain. Further studies could be designed without waiting list control
      and should use a larger sample to clarify the value of qigong compared to
      exercise therapy.

PMID- 21178834
TI  - Unknown Case (Ossification of the Posterior Longitudinal Ligament in the Thoracic
      Spine).

PMID- 21178836
TI  - Improving schoolchildren's knowledge of methods for the prevention and management
      of low back pain: a cluster randomized controlled trial.
AB  - STUDY DESIGN: Cluster randomized controlled trial. OBJECTIVE: To evaluate the
      effect of a very simple education campaign among community-dwelling 8-year-old
      schoolchildren. SUMMARY OF BACKGROUND DATA: Information has a positive effect on
      low back pain (LBP) prevention and management. There is sparse evidence on the
      feasibility and effectiveness of education campaigns focusing on LBP among young
      schoolchildren. METHODS: A stratified random sample of 12 schools was randomized
      to an intervention and a control group. Eight-year-old schoolchildren from these
      schools were given a questionnaire on LBP prevention and management at baseline,
      and 15 and 98 days later. On day 8, teachers in the intervention group gave the
      schoolchildren a Comic Book of the Back, while no intervention was carried out in
      the control group. After adjusting by possible confounders, generalized
      estimating equations (GEE) models were developed to calculate the probability of
      "success" (a score over 80% of the maximum possible one). RESULTS: Six schools
      (231 children, 46.5%) were assigned to the control group, and 6 (266 children,
      53.5%) to the intervention one. At baseline, the percentage of correct answers
      was above 73% in both groups, with 8 as a median total score in the control group
      and 7 in the intervention group. GEE showed that the odds ratio for success in
      the intervention group, when compared with the control group, was 1.61 (95% CI:
      1.03-2.52, P = 0.038). CONCLUSION: The handing out of a Comic Book of the Back
      slightly improves children's knowledge of appropriate methods for the prevention
      and management of LBP, and the effect remains significant 3 months after
      intervention.

PMID- 21178837
TI  - Subclinical autonomic nervous system dysfunction in compressive cervical
      myelopathy.
AB  - STUDY DESIGN: Laboratory evaluation of autonomic nervous system (ANS) in patients
      with cervical compressive myelopathy (CCM). OBJECTIVE: To study the autonomic
      functions and heart rate variability (HRV) in patients with CCM and compare the
      findings after surgery. SUMMARY OF BACKGROUND DATA: ANS dysfunction is well known
      after traumatic spinal cord injury. There are very few studies of ANS dysfunction
      in noncompressive myelopathy and there are no studies on compressive
      myelopathies. METHODS: After excluding patients on cervical traction or with
      medical comorbidities, 29 adult patients with CCM were evaluated. Conventional
      autonomic function tests and HRV were studied in these patients. The same tests
      were done on 29 age- and sex-matched healthy controls. Student t test was used to
      find the significance of study parameters on continuous scale. Chi-square/Fisher
      exact test was used to find the significance of study parameters on categorical
      scale between two groups. Significance was assessed at 5% level. RESULTS:
      Patients with CCM as compared with controls, showed significant difference in
      following parameters; deep breathing, Valsalva ratio, 30:15 (longest RR interval
      (duration between two consecutive R waves of ECG) around 30th second and the
      minimum RR interval around 15 seconds after standing up), and orthostatic fall of
      blood pressure. Except 30:15, there was no significant change of other autonomic
      function tests after surgery. Among the HRV parameters, there was a trend in
      increase in total power and decrease in root-mean-square differences of
      successive RR intervals; however, it did not reach statistical significance.
      CONCLUSION: Patients with CCM have definite ANS dysfunction as compared to
      healthy age- and sex-matched controls. There is significant improvement in 30:15
      ratio after surgery. HRV indices are also impaired and there is a trend for
      change in total power and root-mean-square differences of successive RR intervals
      suggesting loss of HRV.

PMID- 21178838
TI  - Eight-year clinical and radiological follow-up of the Bryan cervical disc
      arthroplasty.
AB  - STUDY DESIGN: Single institution, prospective cohort study of 21 patients who
      underwent single- or bilevel cervical disc arthroplasty for radiculopathy.
      OBJECTIVE: To evaluate the long-term outcome of cervical disc arthroplasty.
      SUMMARY OF BACKGROUND DATA: There is an increasing trend in the use of cervical
      arthroplasty; however, no long-term outcome studies exist to verify their safety,
      functionality, and durability. METHODS: A total of 21 patients underwent 27 total
      disc arthroplasties using the Bryan cervical disc (Medtronic Sofamor Danek Inc,
      Memphis, TN) after anterior cervical discectomy. Clinical and radiological data
      were obtained from the 8-year postoperative review. RESULTS: Nineteen of twenty
      one patients were able to perform daily activities without limitation. Twenty of
      twenty-one patients reported fair to excellent outcome according to Odom criteria
      and 21 of 27 (78%) operated segments were mobile. Functional prostheses moved an
      average of 10.6 degrees , which was similar to the range of movement of the
      adjacent nonoperated segments of the cervical spine. Heterotopic ossification was
      evident in 13 of the 27 (48%) operated segments and restricted movement of the
      prosthesis in nine cases. Five of the six patients who received bilevel
      arthroplasties developed heterotopic ossification. There was one case of
      posterior migration of the prosthesis, which did not have any clinical
      repercussion. No other case showed evidence of migration, subsidence, loosening,
      or wear. Radiological evidence of adjacent segment degeneration was observed in
      four patients (19%); however, each of these patients had pre-existing
      degenerative disc disease at these levels on preoperative imaging. CONCLUSION: At
      8-year follow-up, the Bryan cervical disc arthroplasty maintains favorable
      clinical and radiological results, with preservation of movement and satisfactory
      clinical outcome in the majority of cases. However, the incidence of heterotopic
      ossification causing restricted range of movement of the prosthesis appears to
      increase with time, especially in bilevel procedures.

PMID- 21178839
TI  - Posterior instrumented lumbar spinal surgery in uremic patients under maintenance
      hemodialysis.
AB  - STUDY DESIGN: Clinical retrospective cohort study. OBJECTIVE: To review the
      surgical outcome of instrumented lumbar spinal surgery in uremic patients under
      maintenance hemodialysis and to compare variables between uremic and control
      patients. SUMMARY OF BACKGROUND DATA: Recent advances in maintenance hemodialysis
      have enhanced the quality of life and lifespan of uremic patients. The quality of
      life has markedly increased for uremic patients with instrumented lumbar spinal
      surgery. Thus far, no single study has evaluated the prognosis of uremic patients
      with posterior instrumented lumbar spinal surgery. METHODS: Between 2000 and
      2006, 34 uremic patients with maintenance hemodialysis underwent posterior
      instrumented lumbar spinal surgery. Their medical records, laboratory data, the
      image studies, and the functional outcomes were retrospectively reviewed and
      compared with the variables of a matched control group. RESULTS: Uremic patients
      had significantly lower preoperative hemoglobin and significantly higher
      perioperative packed red blood cell transfusions. The complication rate was
      significantly higher in the uremic patients. The solid fusion rates between the
      two groups were not significantly different. Three-level fusion had a
      significantly lower solid fusion rate than the single-level and two-level
      fusions. The visual analog pain scale and the general outcome assessment were not
      significantly different between the two groups. CONCLUSION: As long as standard
      surgical techniques and perioperative care are performed, the fusion rate and
      functional outcomes in uremic patients can be comparable to those in the normal
      population when undergoing posterior instrumented lumbar spinal surgery. We are
      certain that there will be higher transfusion rate and perioperative
      complications following such a major surgery in uremic patients. Therefore, the
      more extensive the instrumented lumbar spinal surgery is for uremic patients, the
      more closely surgeons should pay attention to preoperative preparation,
      perioperative management, and postoperative care.

PMID- 21178840
TI  - Musculoskeletal modeling of the suboccipital spine: kinematics analysis, muscle
      lengths, and muscle moment arms during axial rotation and flexion extension.
AB  - STUDY DESIGN: In vitro and modeling study of upper cervical spine (UCS) three
      dimensional (3D) kinematics and muscle moment arm (MA) during axial rotation (AR)
      and flexion extension (FE). OBJECTIVE: To create musculoskeletal models with
      movement simulation including helical axis (HA) and muscle features. SUMMARY OF
      BACKGROUND DATA: Integration of various kinematics and muscle data into specific
      specimen 3D anatomical models with graphical representation of HA and muscle
      orientation and MA is not reported for the UCS musculoskeletal system. METHODS:
      Kinematics, anatomical, and computed tomographic imaging data were sampled in 10
      anatomical specimens. Using technical markers and anatomical landmarks
      digitizing, spatial position of segments was computed for five discrete positions
      of AR and FE using a 3D digitizer. To obtain musculoskeletal model simulation, a
      registration method was used to combine collected data. Processing was performed
      using orientation vector and HA computation and suboccipital muscle features
      (i.e., length and MA) relative to motion angle. RESULTS: Range of motion and
      coupling were in agreement with previous in vitro studies. HA (i.e., location and
      orientation) showed low variation at the occipitoaxial and atlantoaxial levels
      for FE and AR, respectively. The main orientation of the HA was vertical at C1-C2
      during AR and horizontal at C0-C1 during FE. For muscles MA, absolute peak value
      (ranging from 20 to 40 mm) occurred at different poses depending on the analyzed
      muscle and motion. Poor magnitude was found for obliquus capitis inferior and
      rectus capitis posterior minor in FE and AR, respectively. CONCLUSION: On the
      basis of previous methods, we developed a protocol to create UCS musculoskeletal
      modeling with motion simulation including HA and suboccipital muscles
      representation. In this study, simultaneous segmental movement displaying with HA
      and muscles features was shown to be feasible.

PMID- 21178841
TI  - Surgical outcome of a posterior approach for large ventral intradural
      extramedullary spinal cord tumors.
AB  - STUDY DESIGN: Case series. OBJECTIVE: The object of this study is to present
      surgical outcomes for treatment of large ventral intradural extramedullary (IDEM)
      spinal cord tumors with conventional laminectomy. SUMMARY OF BACKGROUND DATA:
      Most IDEM spinal cord tumors are meningiomas and schwannomas, which are separated
      from the spinal cord by a discrete anatomical barrier (the arachnoid or pia
      membrane). As a result of this anatomical barrier, a tumor can be removed using
      the posterior approach with conventional laminectomy. Although many reports have
      demonstrated the feasibility of the posterior approach for ventral tumors, there
      have been no studies detailing large ventral IDEM tumors. METHODS: From 2001 to
      2008, we operated on 18 consecutive patients with a large ventral IDEM tumor
      using the posterior approach (8 cervical and 10 thoracic). Preoperatively, eight
      patients were classified as having Nurick grade 1 myelopathy, six patients had
      grade 2, and four had grade 3. Tumors were removed through a slit-like space
      between the dura and spinal cord without retraction of the spinal cord. Complete
      removal of the tumor was possible in 17 cases. The follow-up period was 39 +/- 28
      months (range = 10-97 months). RESULTS: There were 7 cases of meningiomas and 11
      of schwannomas. One schwannoma was mixed with the cervical rootlets and the mass
      in the foramen was left behind. Clinical symptoms improved in 16 patients and
      stabilized in 2. The one residual mass was stable for 62 months. There were no
      cases of recurrence. Neither kyphotic change nor instability developed in any of
      the patients during the follow-up period. CONCLUSION: Large ventral IDEM spinal
      cord tumors can be completely removed using a posterior approach and conventional
      laminectomy. An understanding of the anatomical and growth characteristics of
      these tumors is extremely important for successful removal. However, this
      approach should be applied prudently and with a thorough understanding of its
      limitations.

PMID- 21178842
TI  - Lumbar scoliosis in postmenopausal women: prevalence and relationship with bone
      density, age, and body mass index.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: The aim of this study was to
      investigate the prevalence of lumbar scoliosis in postmenopausal women aged 50
      years and older, and to determine the association of adult lumbar scoliosis with
      age, osteoporosis, and body mass index (BMI). SUMMARY OF BACKGROUND DATA: Adult
      scoliosis prevalence has not been clearly determined. In addition, limited data
      are available on the correlation of adult scoliosis with age, bone mineral
      density, and BMI. METHODS: We studied 380 postmenopausal women aged 50 years and
      older, who were evaluated with dual-energy radiograph absorptiometry (DXA) scan
      images. The lumbar curvature magnitude in the coronal plane was measured in DXA
      images with Cobb's method. Scoliosis was defined by the presence of a curvature
      10 degrees  or larger. Age and T-score in the lumbar spine and in both femoral
      necks were recorded, and BMI was calculated. Correlation analysis among the
      studied variables was performed, as well as a linear regression analysis to
      determine the effect of femoral neck T-score, spine T-score, age, and BMI as
      independent predictors of the Cobb angle in the lumbar spine. RESULTS.: The
      prevalence of lumbar scoliosis was 12.9% (49 cases); 43 cases (11.3%) had lumbar
      curves 10 degrees  or more but less than 20 degrees , and six cases (1.6%) had
      lumbar curves more than 20 degrees . Age and BMI were independent predictors of
      the Cobb angle; the femoral neck T-score and the lumbar T-score were not
      independent predictors of the Cobb angle. CONCLUSION: We found a 12.9% prevalence
      of lumbar scoliosis in postmenopausal women aged 50 years and older, most of them
      with mild curves. Age and BMI are independent predictors of lumbar scoliosis.
      Bone mineral density (BMD) is not an independent predictor of the magnitude of
      the curve.

PMID- 21178843
TI  - Nontraumatic subluxation of the atlanto-axial joint as rare form of acquired
      torticollis: diagnosis and clinical features of the Grisel's syndrome.
AB  - STUDY DESIGN: Case report and review of the literature. OBJECTIVE: We report a
      case of Grisel's syndrome with a delayed diagnosis. The patient's first
      presentation in our pediatric orthopedics department was 2 month after surgery
      (cochlea implantation) with a persistent torticollis. Radiographs revealed a
      subluxated atlantoaxial joint. We treated our patient with manual repositioning
      and calculated antibiotics, which lead to a restitutio ad integrum within a short
      time. SUMMARY OF BACKGROUND DATA: Grisel's syndrome is synonymous with rare
      nontraumatic, rotational subluxation of the atlantoaxial joint (C1-C2). All
      formerly reported cases showed a clear association to infection or were related
      to head and neck surgery. Still, there is a lack of understanding about
      pathogenetic features and causative agents. In 1977 Fielding proposed a
      classification of the atlantoaxial subluxation and stage-related therapy was
      recommended. METHODS: Our patient was a 11-year-old girl with a torticollis after
      insertion of a cochlea implant. After surgery, physiotherapy was performed
      because of her wryneck. As the symptoms did not improve, she was presented in our
      clinic. Our radiographs revealed a subluxated atlantoaxial joint. RESULTS: In
      general anesthesia we performed a manual repositioning and she was temporarily
      immobilized with a cervical collar for 2 weeks. In addition, we administered
      calculated antibiotics, although CRP and leukocytes were not elevated. The follow
      up showed a good repositioning within a short time. CONCLUSION: At least in this
      case, our treatment led to shorter recovery and avoidance of halo fixation. Our
      new therapeutic approach to patients with Grisel's syndrome might lead to a
      shorter recovery.

PMID- 21178844
TI  - Lumbar decompression using a traditional midline approach versus a tubular
      retractor system: comparison of patient-based clinical outcomes.

PMID- 21178845
TI  - Comparison of the kinematic features between the in vivo active and passive
      flexion-extension of the subaxial cervical spine and their biomechanical
      implications.
AB  - STUDY DESIGN: An in vivo motion analysis of active and passive kinematic cervical
      flexion-extension. OBJECTIVE: The study was aimed at investigating the
      differences between the active and passive kinematic sagittal motions of the
      subaxial cervical spine. SUMMARY OF BACKGROUND DATA: The biomechanical behavior
      of the cadaver spinal column is different from that of the in vivo spine. Two
      major issues were concerned: the complex neuromuscular control of the in vivo
      cervical spinal motion and the unknown true nature of the passive cervical spinal
      motion. The kinematic characteristics of active and passive spinal motions need
      to be clarified. METHODS: The active and passive motion patterns of the subaxial
      spine in the sagittal plane were recorded by digital video fluoroscopy. The
      motion of functional units from C3-C4 to C6-C7 of the cervical spine were
      processed using Image J, an image processing software, in both active and passive
      cervical motions. The Cobb's angle was measured in serial flexion and extension
      motions, and a comparison of this angle in both active and passive motions was
      made in 12 patients with degenerative disc herniation. RESULTS: The difference
      between active and passive gentle flexion was minimal, and the degree of their
      correlation was high. The differences in the degree of gentle extension between
      active and passive motion were variable, and their correlation was low. During
      early passive flexion, the degree of flexion at the upper level was less and that
      at the lower level was more as compared to that observed at the respective levels
      in early active flexion. CONCLUSION: In gentle flexion, the active and passive
      cervical spinal motions are closely approximated, which implies that the active
      neuromuscular control mainly plays the buffer-and-brake mechanism without placing
      additional load on the spine. In contrast, the degree of passive extension is
      limited, and active neuromuscular control may place additional load on the spine.

PMID- 21178846
TI  - Human nucleus pulposus cells react to IL-6: independent actions and amplification
      of response to IL-1 and TNF-alpha.
AB  - STUDY DESIGN.: Human nucleus pulposus cells were activated with IL-6 plus IL-6
      soluble receptor (sR) in the presence or absence of IL-1beta or TNF-alpha. Cell
      production of factors modulating the anabolic/catabolic balance of the disc and
      proteoglycan synthesis were determined. OBJECTIVE.: To evaluate NP cell response
      to exogenous IL-6, and how IL-6 modulates IL-1 and TNF-alpha actions in these
      cells. SUMMARY OF BACKGROUND DATA.: Interleukin-6 (IL-6) is produced by cervical
      and lumbar herniated discs and is associated with neurological symptoms of
      intervertebral disc degeneration. It upregulates catabolic gene expression and
      downregulates matrix protein gene expression in chondrocytes. However, no studies
      have evaluated the effects of IL-6 on disc nucleus pulposus (NP) cells. METHODS.:
      NP cells from degenerated human discs were expanded in monolayer, maintained in
      alginate bead culture, and activated with IL-6 plus IL-6 soluble receptor (sR),
      in the presence or absence of IL-1beta or TNF-alpha. Conditioned media was
      collected and analyzed for nitrite, PGE-2, TIMP-1, MMP-3, VEGF, and IL-8.
      Proteoglycan synthesis was assayed as S-sulfate incorporation normalized to DNA
      content and relative gene expression measured by rtPCR. RESULTS.: IL-6 + sR
      decreased collagen and aggrecan message, proteoglycan synthesis, and exacerbated
      the downregulation of proteoglycan synthesis effected by IL-1. PGE-2 synthesis
      was increased by IL-6 + sR, as was the induction of COX-2 mRNA. IL-6 + sR also
      enhanced IL-1 and TNF-alpha stimulated synthesis of PGE-2. IL-6 + sR induced MMP
      3 approximately twofold and increased gene expression and synthesis in cells
      exposed to IL-1 and TNF-alpha. MMP-13 induction by TNF-alpha was also potentiated
      by IL-6 + sR. IL-6 + sR induced IL-6 gene expression and increased that
      stimulated by TNF-alpha fourfold. CONCLUSION.: The results suggest maneuvers to
      diminish IL-6 production in the disc could provide some protection against the
      adverse effects of IL-1 and TNF-alpha, thus, helping preserve disc composition,
      structure, and function.

PMID- 21178847
TI  - Magnetic resonance imaging of the alar and transverse ligaments in acute whiplash
      associated disorders 1 and 2: a cross-sectional controlled study.
AB  - STUDY DESIGN: Cross-sectional. OBJECTIVE: To describe alar- and transverse
      ligament magnetic resonance imaging (MRI) high-signal changes in acute whiplash
      associated disorders (WAD) grades 1 and 2 in relation to the severity and
      mechanics of trauma, and to compare them with controls. SUMMARY OF BACKGROUND
      DATA: The alar and transverse ligaments are important stabilizers at the
      craniovertebral junction. Acute injury of these ligaments should be detected as
      high-signal changes on high-resolution MRI. METHODS: In the study, 114
      consecutive acute WAD 1-2 patients and 157 noninjured controls underwent upper
      neck high-resolution MRI, using proton-weighted sequences and Short Tau Inversion
      Recovery (STIR). Two blinded radiologists independently graded high-signal
      changes 0 to 3 on proton images and assessed ligament high-signal intensity on
      STIR. Image quality was evaluated as good, reduced, or poor (not interpretable).
      Multiple logistic regression was used for both within- and between-groups
      analyses. RESULTS: All proton and STIR images were interpretable. Interobserver
      agreement for grades 2 to 3 versus grades 0 to 1 changes was moderate to good
      (kappa = 0.71 alar; and 0.54 transverse). MRI showed grades 2 to 3 alar ligament
      changes in 40 (35.1%) and grades 2 to 3 transverse ligament changes in 27 (23.7%)
      of the patients. Such changes were related to contemporary head injury (P = 0.041
      alar), neck pain (P = 0.042 transverse), and sex (P = 0.033 transverse) but did
      not differ between patients and controls (P = 0.433 alar; and 0.254 transverse).
      STIR ligament signal intensity, higher than bone marrow, was found in only three
      patients and one control. CONCLUSION: This first study on high-resolution MRI of
      craniovertebral ligaments in acute WAD 1-2 indicates that such trauma does not
      induce high-signal changes. Follow-up studies are needed to find out whether
      pretraumatic high-signal changes imply reduced ligament strength and can predict
      chronic WAD.

PMID- 21178848
TI  - The reliability of the ball-tipped probe for detecting pedicle screw tract
      violations prior to instrumenting the thoracic and lumbar spine.
AB  - STUDY DESIGN: Cadaveric. OBJECTIVE: To determine the confidence with which
      surgeons should rely on a flexible ball-tipped probe to detect pedicle breeches
      in the thoracic and lumbar spine. SUMMARY OF BACKGROUND DATA: The reliability of
      a ball-tipped probe for detecting cortical violations of the pedicle tract has
      not been studied among fellowship-trained surgeons. METHODS: A total of 134
      pedicles were randomized to have pedicle screw tracts with one of six possible
      options: no violation, anterior, superior, inferior, medial, or lateral
      violations. Five fellowship-trained spine surgeons examined each pedicle, using a
      standard flexible ball-tipped probe on three nonsequential occasions. The
      percentage of correctly identified violations, sensitivity, specificity, positive
      predictive value, and negative predictive value were calculated for the surgeons
      as a group and individually. The Cohen kappa coefficient was used to assess the
      accuracy of the observers and the interobserver and intraobserver agreement.
      Finally, we analyzed our results by spinal region to see whether this impacted
      the surgeons' ability to detect a pedicle violation. RESULTS: The surgeons were
      able to correctly identify 81% of intact pedicles, 39% of superior, 68% of
      medial, 74% of lateral, 62% of anterior, and 50% of inferior violations. The
      sensitivity varied considerably by breech location and surgeon with a range of
      18% to 85%. Positive predictive value for each breech location ranged from 12% to
      20%. The specificity was 81% and negative predictive value 98% overall. The
      intraobserver reliability was moderate and interobserver reliability was low in
      this series. The ability to detect a pedicle violation was significantly better
      in the lower thoracic region (T6-T12) than in other areas of the spine.
      CONCLUSION: The standard ball-tipped probe was much less reliable than expected.
      This technique can be used to confirm an intact pedicle but has an unacceptably
      high false-positive rate and should be used with caution. Our study suggests that
      overconfidence in pedicle probing might be dangerous.

PMID- 21178849
TI  - Progression of cervical spine instabilities in rheumatoid arthritis: a
      prospective cohort study of outpatients over 5 years.
AB  - STUDY DESIGN: A 5-year prospective cohort study of cervical spine instabilities
      in rheumatoid arthritis (RA). OBJECTIVE.: To clarify the natural course of
      cervical instabilities in RA patients and to determine predictors for the
      prognosis of RA cervical spine. SUMMARY OF BACKGROUND DATA: Although several
      previous studies investigating the natural history of RA cervical spine have been
      reported, few of them have described radiological predictive factors for the
      aggravation of these instabilities. METHODS: Two hundred sixty-seven outpatients
      with "definite" or "classical" RA initially assigned were prospectively followed
      for over 5 years. Radiographic cervical findings were classified into three
      representative instabilities: atlantoaxial subluxation (AAS), vertical
      subluxation (VS), and subaxial subluxation (SAS). The aggravations of these
      instabilities were identified in the cases with a decrease of at least 2 mm in
      the Ranawat value of VS, an increase of at least 1 mm in translation of SAS, or a
      new development of respective instabilities. RA stages and mutilating changes
      were assessed in the hand radiograms. RESULTS: Fifty-two point four percent of
      267 patients, without any cervical instability at the beginning of follow-up,
      decreased to 29.6% at the end (P < 0.01), whereas VS and SAS increased
      significantly (P < 0.01). The aggravation of VS was observed at statistically
      higher rates in patients with pre-existing instabilities as follows; 25.7% of AAS
      (P = 0.01), 49.1% of VS (P < 0.01), and 41.2% of SAS (P = 0.06). The aggravation
      of SAS was also detected in 47.2% of VS and 64.7% of SAS (P < 0.01). Patients
      with pre-existing mutilating changes exhibited the aggravations of VS and SAS in
      significantly higher incidences (P < 0.01). Furthermore, the cases with
      development into mutilating changes during the follow-up showed significantly
      higher tendencies for the aggravations of these instabilities (P < 0.01).
      CONCLUSION: The incidences of VS and SAS significantly increased during the
      minimum 5-year follow-up. Prognostic factors of these instabilities were revealed
      to be the initial radiological findings of VS, SAS, and mutilating changes.

PMID- 21178850
TI  - Use and outcome of MRI in the surgical treatment of adolescent idiopathic
      scoliosis.
AB  - STUDY DESIGN: Multicenter, prospective, consecutive clinical series. OBJECTIVE.:
      To report on the use and outcomes of preoperative magnetic resonance imaging
      (MRI) in a prospective cohort study of 2206 children undergoing posterior spinal
      fusion and instrumentation for adolescent idiopathic scoliosis. SUMMARY OF
      BACKGROUND DATA: There is no consensus on the use of MRI in the preoperative
      evaluation of children with idiopathic scoliosis. Also, there is no consensus on
      the rate of abnormality and the relevance of abnormality on surgical outcome in
      so-called "idiopathic" scoliosis. METHODS: We reviewed the first 2206 patients
      entered consecutively into the Prospective Pediatric Scoliosis Study, a database
      of children (8-18 years) undergoing operation for scoliosis by pediatric spinal
      surgeons in the Spinal Deformity Study Group. RESULTS: There were 1812 girls
      (80.8%) and 394 boys (17.5%). Mean age at operation was 14 years and 3 months. A
      total of 191 (8.6%) had juvenile idiopathic scoliosis (age <= 10 years). A total
      of 923 patients (41.8%) underwent spine MRI. Ninety-one abnormalities of the
      spine were detected (9.9% of the 923 screened), of which 39 (4.2%) were neural.
      There were 26 syringes (66.7% of neural abnormalities and 28.6% of all
      abnormalities), 12 Chiari malformations (30.7% and 13.2%, respectively), and 1
      tethered cord (2.6% and 1.1%, respectively). Fifty-three patients (5.7%)
      demonstrated abnormalities affecting "other" parts of the spine than the neural
      elements. Patients undergoing MRI more frequently had a thoracic hyperkyphosis (P
      < 0.001), had a diagnosis of juvenile idiopathic scoliosis (P < 0.001), had a
      Risser grade between 0 and 2 (P = 0.022), had a greater curve magnitude (P <
      0.001), had three major curves (P < 0.001), were male (P = 0.004), and underwent
      a combined anterior-posterior surgical approach (P < 0.001). Thoracic
      hyperkyphosis and juvenile onset were associated with greater chance of neural
      lesion on MRI of the spine. Incidence of abnormal MRI did not differ
      significantly by direction of apex, Risser grade, curve magnitude or type, male
      sex, or body mass index. CONCLUSION: Use of preoperative MRI was 41.8%; 9.9% of
      patients with so-called "idiopathic" scoliosis had an abnormality on MRI, of
      which 4.2% were neural anomalies. Of these, syrinx was 66.7%, Chiari was 30.7%,
      and tethered cord was 2.6%. Significant risk factors for neural abnormality were
      thoracic hyperkyphosis and juvenile onset. Other characteristics, including apex
      left thoracic curve, Risser less than or equal to 1, large curve magnitude,
      triple major curve, male sex, and obesity were not associated with neural
      abnormality. There were no differences in complication rates between normal and
      abnormal MRI patients. Our data question the routine use of MRI as a screening
      tool for adolescent idiopathic scoliosis.

PMID- 21178851
TI  - Surgical complications are associated with omission of chemotherapy for stage III
      colorectal cancer.
AB  - PURPOSE: Appropriate use of adjuvant chemotherapy is a widely recognized quality
      measure of colorectal cancer care. The objective of this study was to test the
      hypothesis that surgical complications are associated with omission of
      chemotherapy for colorectal cancer. METHODS: We used the 1998 to 2005
      Surveillance, Epidemiology and End Results-Medicare database to study adjuvant
      chemotherapy use among patients with stage III colorectal cancer who underwent
      surgical resection. Chemotherapy use was compared between patients with and
      without complications. Univariate analyses and multiple logistic regression were
      used to test the association between complications and chemotherapy omission,
      while adjusting for demographics, comorbidity, and other factors. Associations
      between complications and time to chemotherapy were also studied. RESULTS: We
      identified 17,108 eligible patients with stage III colorectal cancer (median age,
      75 y; 24% rectal/rectosigmoid). Using a parsimonious list of complication codes,
      18% of patients had >= 1 complication. Thirteen percent of patients had medical
      complications and 3.8% of patients had complications requiring reoperation or
      another procedure. Adjuvant chemotherapy was omitted among 46% of patients with
      complications, compared with 31% of patients with no complications (P < .0001).
      Having a complication was independently associated with omission of chemotherapy
      in multivariable analysis (adjusted OR, 1.76; 95% CI 1.59-1.95). Other factors
      significantly associated with chemotherapy omission were age, race, marital
      status, urgent/emergent admission, and type of operation. Risk ratios increase
      with multiple complications (P < .0001). Complications were also associated with
      an increased risk of chemotherapy delay (P < .0001). CONCLUSIONS: Surgical
      complications are independently associated with omission of chemotherapy for
      stage III colorectal cancer and with a delay in adjuvant chemotherapy. These data
      suggest that complications of colorectal surgery may affect both short- and long
      term cancer outcomes. Thus, the implementation of quality improvement measures
      that effectively reduce perioperative complications may also provide a long-term
      cancer survival benefit.

PMID- 21178852
TI  - Improving the quality of colon cancer surgery through a surgical education
      program.
AB  - PURPOSE: Recent evidence has demonstrated the importance of dissection in the
      correct tissue plane for the resection of colon cancer. We have previously shown
      that meticulous mesocolic plane surgery yields better outcomes and that the
      addition of central vascular ligation produces an oncologically superior specimen
      compared with standard techniques. We aimed to assess the effect of surgical
      education on the oncological quality of the resection specimen produced. METHODS:
      We received clinicopathological data and specimen photographs from 263 resections
      for primary colon cancer from 6 hospitals in the Capital and Zealand regions of
      Denmark before a national training program. Ninety-three cases were from Hillerod
      Hospital, where surgeons had previously implemented a surgical educational
      training program in complete mesocolic excision with central vascular ligation
      and adopted the procedure as standard practice. The specimen photographs were
      assessed for the plane of surgery and tissue morphometry was performed. RESULTS:
      Hillerod specimens had a higher rate of mesocolic plane surgery (75% vs 48%; P <
      .0001) compared with the other hospitals. The surgeons at Hillerod Hospital also
      removed a greater length of colon in both fresh (median, 315 vs 247 mm; P <
      .0001) and fixed (269 vs 207 mm; P < .0001) specimens with a greater distance
      between the tumor and the closest vascular tie in both fresh (105 vs 84 mm; P =
      .006) and fixed (82 vs 67 mm; P = .002) specimens. This resulted in the removal
      of more mesentery in both fresh (14,466 vs 8706 mm; P < .0001) and fixed (9418 vs
      6789 mm; P < .0001) specimens and a greater median lymph node yield (28 vs 18; P
      < .0001). CONCLUSIONS: We have shown that adoption of complete mesocolic excision
      with central vascular ligation results in a change to the production of an
      oncologically superior specimen compared with standard techniques. This should
      improve outcomes toward those reported by centers that have long practiced
      meticulous colon cancer surgery.

PMID- 21178853
TI  - Magnetic anal sphincter augmentation for the treatment of fecal incontinence: a
      preliminary report from a feasibility study.
AB  - BACKGROUND: Magnetic sphincter augmentation, a successful treatment of
      gastroesophageal reflux disease, has been applied to treat fecal incontinence.
      The purpose of this feasibility study was to understand the safety profile as
      well as the potential benefit of this new device when it is implanted in patients
      with fecal incontinence. METHODS: A magnetic anal sphincter device was surgically
      implanted in candidates with documented fecal incontinence of more than 2
      episodes per week at 3 investigational centers in Europe and the United States
      following ethics/institutional review board approval. The magnetic anal sphincter
      device was placed around the anal canal via a single anterior incision. All data
      were collected prospectively. The primary outcome measure was the reduction of
      incontinent episodes based on a daily continence diary. RESULTS: To date 14
      patients have been implanted with the device (all female; mean age, 62.8 y;
      range, 41-74 y) with a median follow-up of 6 months. There have been no
      intraoperative complications. Mean hospital stay was 3 days; range, 1 to 7 days.
      Adverse events were observed in 7 patients. Three patients are no longer
      implanted with a device; 2 devices were removed and one passed spontaneously
      following a separation at the suture connection. Five patients with 6-month
      follow-up demonstrated a mean reduction in the number of average weekly
      incontinence episodes from 7.2 to 0.7 (90.9%) and a mean reduction in Wexner
      Continence Score from 17.2 to 7.8 (54.7%). Compared with baseline, quality of
      life improved in all 4 domains of the fecal incontinence quality of life (FIQoL)
      scoring system. No patients have reported that their condition has worsened. Two
      patients at 1-year follow-up both reported perfect continence. CONCLUSION: This
      preliminary study describes the use of a new device to treat fecal incontinence.
      Compared with existing devices, implantation is simple and it requires no
      adjustments from the physician or patient once the device is implanted. Initial
      assessment with a small number of patients shows promising outcomes with a
      limited incidence of complications and good restoration of continence.

PMID- 21178854
TI  - Total mesorectal excision for rectal cancer: the potential advantage of robotic
      assistance.
AB  - PURPOSE: The purpose of this study was to analyze the safety, feasibility, and
      efficacy of the da Vinci S HD robotic system in mesorectal excision for rectal
      adenocarcinoma, with the aim to identify areas of potential advantage for the
      robot in this procedure. METHODS: This study was conducted as a retrospective
      review of a prospectively maintained database of 44 consecutive cases of robot
      assisted mesorectal excision for rectal adenocarcinoma performed between August
      2005 and February 2010. Patient demographics, perioperative outcomes, and
      complications were evaluated and compared with similar published reports and
      relevant literature. RESULTS: There were 28 (63.6%) men and 16 (36.4%) women,
      with a mean age of 63 years. The majority of patients were either overweight or
      obese and 88.7% of lesions were in the mid or low rectum. We performed 36 low
      anterior resections (6 intersphincteric) and 8 abdominoperineal resections with a
      median blood loss of 150 mL (range, 50-1000), a median operative time of 347
      minutes (range, 155-510), and a median length of stay of 5 days (range, 3-36).
      The median lymph node yield was 14 (range, 5-45) and the circumferential
      resection margin was negative in all patients. We had 1 distal margin positivity
      (2.7%), 2 anastomotic leaks (5.6%), 1 death (2.7%), and 2 conversions (4.5%) to
      the open approach. No robot-associated morbidity occurred in this series.
      CONCLUSIONS: This series compares favorably with similar published reports with
      regard to the safety and feasibility of robotic assistance in total mesorectal
      excision for rectal cancer. The lower conversion rates reported for robotic
      rectal resection compared with laparoscopy require validation in large randomized
      trials.

PMID- 21178855
TI  - The Altemeier procedure for rectal prolapse: an operation for all ages.
AB  - PURPOSE: Perineal rectosigmoidectomy was the most popular operation performed for
      rectal prolapse in the first half of the 20th century. However, high recurrence
      rates relegated it to a back-up role for elderly or other high-risk patients who
      were not candidates for an abdominal operation. Recent series (combined with
      levatorplasty = Altemeier procedure) revealed excellent results across a broader
      spectrum of patients and inspired this ongoing consecutive series of cases.
      METHODS: This is a review of 103 (99 women) consecutive patients (mean age, 68.9
      y; range, 20-97 y) who underwent the Altemeier procedure between 2000 and 2009.
      Patients were placed in the prone jackknife position: 93 patients (90%) with the
      use of general anesthesia and 10 patients (10%) with the use of spinal
      anesthesia. The mean follow-up was 43 months (range, 3 mo to 10 y). RESULTS: The
      mean time for the operation was 97.7 minutes (range, 50-180 min) with a mean 7.2
      cm of rectum resected (range, 2.5-26.7 cm). The mean blood loss was 66.9 mL
      (range, 0-350 mL). The mean time to tolerating a diet was 2.3 days (100% within 4
      d) and mean postoperative length of hospital stay was 4.2 days (93% within 6 d).
      There was no mortality, minimal morbidity (14%), and no recurrence. Preoperative
      constipation (61% of patients) improved in 94% and preoperative fecal
      incontinence (47% of patients) improved in 85%, whereas 15% developed new onset
      of seepage or incontinence to flatus. CONCLUSIONS: The Altemeier procedure for
      rectal prolapse provided excellent results across all age groups with minimal
      morbidity, allowing for short hospital stays and periods of convalescence. To
      this point, there has been no evidence of recurrence in this group of patients,
      pending longer periods of follow-up, especially among patients from the younger
      age groups.

PMID- 21178856
TI  - Is local excision after complete pathological response to neoadjuvant
      chemoradiation for rectal cancer an acceptable treatment option?
AB  - PURPOSE: The role of local excision in patients with good histological response
      to neoadjuvant chemoradiation for locally advanced rectal cancer is unclear,
      mainly because of possible regional nodal involvement. This study aims to
      evaluate the correlation between pathological T and N stages following
      neoadjuvant chemoradiation for locally advanced rectal cancer and the outcome of
      patients with mural pathological complete response undergoing local excision.
      METHODS: This investigation was conducted as a retrospective analysis. Between
      January 1997 and December 2007, 320 patients with T3 to 4Nx, TxN+ or distal (<= 6
      cm from the anus) T2N0 rectal cancer underwent neoadjuvant concurrent
      chemoradiation followed by surgery. Radiotherapy was standard and chemotherapy
      consisted of common fluoropyrimidine-based regimens. RESULTS: After
      chemoradiation, 93% patients had radical surgery, 6% had local excision, and 3%
      did not have surgery. In the 291 patients undergoing radical surgery, the
      pathological T stage correlated with the N stage (P = .036). We compared the
      outcome of patients with mural complete pathological response (n = 37) who
      underwent radical surgery (group I) and those (n = 14) who had local excision
      only (group II). With a median follow-up of 48 months, 4 patients in group I had
      a recurrence and none in group II had a recurrence; one patient died in group I
      and none died in group II. Disease-free survival, pelvic recurrence-free
      survival, and overall survival rates were similar in both groups. CONCLUSION: In
      this retrospective study, nodal metastases were rare in patients with mural
      complete pathological response following neoadjuvant chemoradiation (3%), and
      local excision did not compromise their outcome. Therefore, local excision may be
      an acceptable option in these patients.

PMID- 21178857
TI  - Permanent stoma after low anterior resection for rectal cancer.
AB  - BACKGROUND AND OBJECTIVES: A low anterior resection procedure for removing a
      rectal tumor aims to preserve the sphincter and avoid a permanent stoma.
      Permanent stomas are primarily necessary in cases of poor anorectal function and
      local recurrence. The aim of this study was to clarify whether anastomosis
      related complications and local recurrence influenced the rate of permanent
      stomas in a long-term follow-up. METHODS: Of 1032 consecutive patients with
      rectal cancer, 397 were treated by low anterior resection (R0 and R1 resections)
      between 1985 and 2007 at the Department of General and Abdominal Surgery of the
      University Hospital, Mainz (Germany). All patient data were collected
      prospectively. A retrospective, multivariate analysis was conducted to determine
      factors that influenced the occurrence of delayed and nonreversal of
      defunctioning stoma, the rate of repeat stoma after closure, and the need for a
      permanent stoma in patients whose stomas were not initially defunctioning.
      RESULTS: A defunctioning stoma was created in 292 of 397 patients (74%); 12% of
      stomas were not reversible (33/279 that survived the operation >90 d); 11%
      (28/246) required a repeat stoma after stoma closure; 10% (10/105) of patients
      whose stomas were not initially defunctioning received a late permanent stoma.
      The overall rate of a permanent stoma was 18%. The main reasons for a permanent
      stoma were anastomosis-related complications and local recurrence. Risk factors
      for anastomosis-related complication were male gender, low tumor site, and tumor
      stage. Despite a significant reduction in local recurrence rates from 1997 to
      2007, the rate of creating a permanent stoma did not change. CONCLUSIONS: The
      possibility of a permanent stoma should be considered when planning surgery for
      treating rectal cancer. It might be preferable in older patients, in poor
      condition and with more advanced rectal cancers, to consider an abdominoperineal
      resection or Hartmann procedure instead of a low anterior resection.

PMID- 21178858
TI  - Anatomical lymph node mapping in normal mesorectal adipose tissue.
AB  - PURPOSE: In view of divergent outcomes of surgery for rectal cancer despite
      standard protocols, the aim of this study was to provide a basis for improving
      lymph node assessment by defining the number, shape, and distribution of all
      lymphatic structures in the mesorectum. METHODS: Cadavers from 6 males and 6
      females who died from causes other than colorectal or neoplastic pathologies were
      studied. Rectum and mesorectum were excised en bloc. The adipose tissue was
      separated from the rectum and divided into 9 sections before fixing the specimen
      in paraffin, cutting into smaller portions, and staining with hematoxylin and
      eosin. Slides were analyzed with an optical microscope, and identified lymph
      nodes were counted in each section. RESULTS: The mean age of the deceased was
      52.7 (range, 26-65) years. No evidence of previous history of neoplastic
      pathology or any type of premortal colorectal inflammatory process was found. A
      total of 412 lymph nodes were identified, with a mean of 34.3 (SD, 2.1; range, 31
      37) lymph nodes per cadaver. The mean number of lymph nodes differed
      significantly across levels of the mesorectum, with 22.2 lymph nodes in the
      upper, 9.8 in the middle, and 2.3 in the lower sections; 266 (64.6%) of all lymph
      nodes were located in the upper third of the mesorectum. Distribution density was
      higher in the proximal posterior sections, with 197 lymph nodes (47.8%) in the
      upper 2 thirds of the posterior mesorectum. Node diameter was less than 5 mm in
      330 (80%) of 412 nodes. CONCLUSIONS: Our study confirmed that more than 30 lymph
      node units normally exist in the mesorectal area. In view of previous studies
      demonstrating advantages of increasing the number of lymph nodes evaluated,
      staging of rectal cancer might be improved by counting more than 12 lymph nodes
      per specimen.

PMID- 21178859
TI  - The rate of abdominoperineal resections for rectal cancer in the state of
      Victoria, Australia: a population-based study.
AB  - PURPOSE: The aim of this study was to document a population-based rate of
      abdominoperineal resections for adenocarcinoma of the rectum in the state of
      Victoria, Australia. It also determined whether surgeon caseload or specialist
      colorectal training affects this rate. METHODS: All resections for adenocarcinoma
      of the rectum (International Classification of Diseases for Oncology, 3rd edition
      C20) that were performed in Victoria in the year 2005 were included. Procedures
      for rectosigmoid or colon cancer were excluded. The sample was taken from the
      Victorian Cancer Registry. The rate of abdominoperineal resections was calculated
      by dividing the total number of abdominoperineal resections by the total number
      of procedures for rectal cancer. Mixed-effects logistic regression was used to
      estimate the odds ratio for surgeon caseload and specialist colorectal training.
      RESULTS: There were 582 resections available for analysis. Patients were mostly
      males (66%) and over 60 years of age (67.7%). The overall rate of
      abdominoperineal resection was 23.4%. The rate of abdominoperineal resections for
      low rectal cancers was lower (42.8%) among surgeons who had specialist colorectal
      training compared with those who did not (60.6%) (OR = 2.06; 95% CI, 1.24-3.42).
      CONCLUSION: The rate of abdominoperineal resection in Victoria for 2005 was
      23.4%. Patients with low rectal cancer operated on by surgeons who had had
      specialist colorectal training were significantly less likely to undergo an
      abdominoperineal resection compared with patients undergoing an operation by
      surgeons who did not have specialist colorectal training.

PMID- 21178860
TI  - Sphincter-preserving fistula management: what patients want.
AB  - PURPOSE: The purpose of this study was to determine how patients with anal
      fistulas would rank clinical scenarios describing various management options for
      anal fistulas. METHOD: A survey was administered to 74 consecutive patients with
      anal fistulas. On each survey, 10 clinical scenarios describing various treatment
      options for anal fistulas were scored from 1 (most likely to select) to 10 (least
      likely to select). Mean scores for each scenario were calculated and compared by
      use of a Student t test. RESULTS: When combined, 74% of patients selected a
      sphincter-preserving technique as their primary choice compared with 26% who
      chose a fistulotomy (P < .0001). Compared with the highest ranking sphincter
      preserving techniques, the mean scores of the scenarios involving a fistulotomy
      were significantly (P < .05) lower (less likely to select). The mean score of a
      traditional fistulotomy was the same as the mean score of a sphincter-preserving
      technique with a 50% success rate but no risk of diminished continence.
      CONCLUSIONS: These data suggest that the majority of patients with an anal
      fistula will select a sphincter-preserving technique to manage their fistula.
      This finding may indicate that, within limits, it is of greater importance for
      most patients to minimize their risk of diminished continence than to have a
      highly successful treatment strategy for their fistula.

PMID- 21178861
TI  - The digital rectal examination scoring system (DRESS).
AB  - PURPOSE: Assessment of anal sphincter tone is a critical part of anorectal
      examination, yet no standardized, quantifiable method for describing anal
      sphincter tone on digital rectal examination exists. We developed a novel scoring
      system for anal sphincter tone using a scale of 0 to 5 for both resting pressure
      and squeeze pressure. The score ranges from 0 = no discernable pressure to 5 =
      extremely tight and 3 = normal. We hypothesized that the digital rectal
      examination scoring system (DRESS) score would correlate with anorectal manometry
      pressures. METHODS: Three hundred three patients (mean age, 51 y; range, 28-86 y)
      who had a DRESS score and a concurrent manometry test (1998-2008) were identified
      from a prospective database. Means of 4 quadrant manometry at rest and with
      squeeze were compared with the resting pressure and squeeze pressure DRESS scores
      at each point from 0 to 5. Box plots for manometry results by DRESS score were
      graphed. ANOVA using a significance level of alpha = .05 tested whether each of
      the DRESS scores were different from one another. Spearman rank correlation
      coefficients assessed associations between manometry and DRESS results. RESULTS:
      Manometric pressures (mmHg; mean +/- SEM) for DRESS resting pressure values 0 to
      5 were 20.6 +/- 2.1, 38.5 +/- 2.0, 47.8 +/- 1.6, 72.3 +/- 1.5, 94.4 +/- 2.9, and
      128.0 +/- 6.7, respectively. Pressures for DRESS squeeze pressure values 0 to 5
      were 45.9 +/- 5.6, 66.5 +/- 3.2, 108.2 +/- 4.9, 156.3 +/- 4.5, 238.6 +/- 9.8, and
      368.2 +/- 49.1. Box plots demonstrated clear differences between each DRESS score
      and positive progression from 0 to 5 for both resting pressure and squeeze
      pressure. ANOVA analysis showed a significant difference in mean manometry
      measurements at all levels of digital rectal examination, both for resting
      pressure and squeeze pressure (P < .001). Spearman rank correlations showed a
      strong positive correlation between the DRESS values and manometry pressures with
      coefficients of 0.82 for resting pressure and 0.81 for squeeze pressure.
      CONCLUSIONS: The DRESS score correlated very well with manometry pressures for
      resting pressure and squeeze pressure. The DRESS system may be a useful
      description of anal sphincter resting pressure and squeeze pressure in the
      clinical setting. Further validation may support adoption of the DRESS system as
      part of the standard anorectal examination.

PMID- 21178862
TI  - Sacral neuromodulation for the treatment of fecal incontinence: analysis of cost
      effectiveness.
AB  - PURPOSE: The cost-effectiveness and budget impact of introducing sacral nerve
      modulation (SNM) as a treatment for fecal incontinence in Italy were evaluated in
      a simulation model. METHODS: A decision-analysis model with a Markov submodel was
      used to represent clinical pathways for treatment of patients with fecal
      incontinence in a scenario with SNM and a scenario without SNM. Data were
      obtained from published studies and from an expert panel. Evaluation of resource
      consumption was conducted from the perspective of the Italian National Health
      Service, and costs were retrieved from the Italian NHS procedures reimbursement
      list. The time horizon was 5 years, and a 3% discount rate was applied to costs
      and outcomes. Effectiveness was measured in symptom-free years and in quality
      adjusted life-years (QALYs). Fecal incontinence prevalence data and SNM usage
      forecasts were used to estimate budget impact over the next 5 years. RESULTS: The
      incremental cost-effectiveness ratio for introducing SNM was ?28,285 per QALY
      gained for patients with a structurally deficient anal sphincter and ?38,662 per
      QALY gained for patients with intact anal sphincters. If a threshold of ?40,000
      per QALY gained is set as the level that a decision-maker would regard as cost
      effective, the probability that the introduction of SNM will be cost-effective
      would be 99% for patients with a structurally deficient sphincter and 53% for
      patients with an intact sphincter. Budget impact analysis showed that introducing
      SNM would have an estimated budget impact of 0.56% over 5 years on the budget
      allocated for fecal incontinence treatment. CONCLUSION: Our data show SNM to be
      an efficient investment with an acceptable incremental cost-effectiveness ratio
      and a limited impact on the total allocated budget for fecal incontinence.

PMID- 21178863
TI  - Rectum-sparing surgery may be appropriate for biallelic MutYH-associated
      polyposis.
AB  - PURPOSE: The risk of cancer or severe polyposis of the rectal stump after total
      colectomy for MutYH-associated polyposis is scarcely defined. To evaluate this
      risk, we describe the findings of endoscopic surveillance of the rectal stump in
      a series of patients with biallelic MutYH mutations and polyposis. METHODS: This
      is a retrospective, observational, multicenter case series derived from 2
      familial cancer registries. Biallelic, germ-line MutYH mutations were found in 14
      patients with no adenomatous polyposis coli gene mutations. Eleven of them
      underwent total colectomy with ileorectal anastomosis and yearly proctoscopic
      surveillance thereafter. Phenotype and histology of rectal polyps were recorded
      at diagnosis and during follow-up. Development of adenomas and carcinomas during
      endoscopic surveillance of the rectal stump was observed. RESULTS: At diagnosis,
      6 patients had attenuated polyposis (10-100 adenomas), 5 patients had classical
      polyposis, 8 patients had colon carcinoma, and no patient had rectal carcinoma.
      The mean number of rectal polyps at diagnosis was 2.64 +/- 2.11 (range, 0-6). No
      patients had rectal cancer. The most frequent MutYH mutations were Y165C/Y165C
      and G382D/G382D in 6 and 2 patients, respectively. During surveillance of the
      rectal stump after surgery (median duration, 5 y; range, 2-23 y), no patient
      developed rectal cancer. The mean number of adenomas per proctoscopy was 1.23 +/-
      2.19 (range, 0-10 adenomas per proctoscopy). This study was limited by the small
      size and retrospective nature of the case series. CONCLUSION: Total colectomy
      with ileorectal anastomosis may be appropriate for patients with MutYH-associated
      polyposis, provided that they have no rectal cancer or severe rectal polyposis at
      presentation and that they undergo yearly endoscopic surveillance thereafter.

PMID- 21178864
TI  - E durans strain M4-5 isolated from human colonic flora attenuates intestinal
      inflammation.
AB  - PURPOSE: The aim of this study was to evaluate in vitro and in vivo effects of a
      unique high-butyrate-producing bacterial strain from human colonic flora,
      Enterococcus durans, in prevention and treatment of intestinal inflammation.
      METHODS: A compartmentalized Caco-2/leukocyte coculture model was used to examine
      the in vitro effects of E durans and its metabolite butyrate on basal and
      Escherichia coli-stimulated secretion of proinflammatory immune factors (IL-8, IL
      6, and TNF-alpha) and the anti-inflammatory cytokine IL-10. A murine model of
      dextran sodium sulfate-induced colitis was used to examine in vivo effects of
      prevention and therapy with E durans on clinical, biochemical, and histologic
      parameters of inflammation. RESULTS: In the coculture model, treatment with E
      durans and with butyrate reduced basal as well as E coli stimulated secretion of
      IL-8, IL-6, and TNF-alpha and increased secretion of IL-10. In the in vivo murine
      model, preventive administration of E durans significantly ameliorated clinical
      disease activity index (weight loss, fecal bleeding, and stool consistency),
      reduced myeloperoxidase concentration in colon tissue extracts, improved
      histologic scores of colonic inflammation, and inhibited colonic transcription of
      proinflammatory immune factors. The effect of therapeutic treatment alone on
      these parameters was more moderate but still significant. CONCLUSIONS: We
      conclude that E durans strain M4 to 5 and its metabolic product butyrate induce
      significant anti-inflammatory effects, mediated by regulation of pro- and anti
      inflammatory immune factors as well as preservation of intestine epithelial
      integrity, suggesting that this novel anti-inflammatory bacterium may be
      preferentially a useful prophylactic treatment to avoid inflammatory bowel
      disease.

PMID- 21178865
TI  - Expression of estrogen and progesterone receptors in the anal canal of women
      according to age and menopause.
AB  - PURPOSE: Fecal incontinence is highly prevalent, especially in menopausal women.
      The aim of this study was to analyze the expression of estrogen and progesterone
      receptors in the anal canal of women in relation to menopausal status and age.
      METHODS: Samples of hemorrhoidal tissue were obtained from 34 women undergoing
      hemorrhoidectomy. The patients were divided into 2 groups: group 1 consisted of
      women with a menstrual cycle (n = 17) and group 2 consisted of postmenopausal
      women (n = 17). Immunostaining of hormone receptors was performed using specific
      antibodies (DAKO, Copenhagen, Denmark) in cells from the internal anal sphincter,
      the vascular epithelium, and the squamous epithelium. The percentage of
      positivity of receptors and the association between age and receptor positivity
      were compared between the 2 groups. RESULTS: Estrogen receptors were found in the
      internal anal sphincter in 23.5% in group 1 vs 11.8% in group 2 (P = .656).
      Progesterone receptors were found in 41.2% in group 1 vs 11.8% of group 2 (P =
      .118). Squamous epithelium showed estrogen receptors in 52.9% in group 1 vs 64.7%
      of group 2 (P = .388) and progesterone receptors in 17.6% and 0% in groups 1 and
      2, respectively (P = .227). Vascular endothelium showed no receptors. Receptor
      positivity was not associated with age. CONCLUSION: No significant differences
      were found in the detection of estrogen and progesterone receptors in structures
      of the anal canal in women in relation to menopausal status and age.

PMID- 21178866
TI  - Complete clinical response after neoadjuvant chemoradiation therapy for distal
      rectal cancer: characterization of clinical and endoscopic findings for
      standardization.
AB  - BACKGROUND: Complete tumor regression may develop after neoadjuvant
      chemoradiation therapy for distal rectal cancer. Studies have suggested that
      selected patients with complete clinical response may avoid radical surgery and
      close surveillance may provide good outcomes with no oncologic compromise.
      However, definition of complete clinical response is often imprecise and may vary
      between different studies. The aim of this study is to provide a clear definition
      for a complete clinical response after neoadjuvant chemoradiation therapy in
      patients with distal rectal cancer in addition to actual endoscopic videos from
      patients managed nonoperatively. METHODS: Patients with nonmetastatic distal
      rectal cancer treated by neoadjuvant chemoradiation therapy, including 50.4 Gy
      and concomitant 5-fluorouracil and leucovorin, were assessed for tumor response
      at least 8 weeks after chemoradiation therapy completion. Complete and incomplete
      clinical responses were defined based on clinical and endoscopic findings.
      Patients with complete clinical response were not immediately operated on and
      were closely followed. Early and late endoscopic findings were recorded. RESULTS:
      Definition of a complete clinical response should be based on very strict
      clinical and endoscopic criteria. The finding of any residual superficial
      ulceration, irregularity, or nodule should prompt surgical attention, including
      transanal full-thickness excision or even a radical resection with total
      mesorectal excision. Standard or incisional biopsies should be avoided in this
      setting. Complete clinical responders should harbor no more than whitening of the
      mucosa, teleangiectasia with mucosal integrity to be considered for a
      nonoperative approach. In the presence of these findings, regularly scheduled
      reassessments may provide a safe alternative to these patients with early
      detection of recurrent disease. CONCLUSION: Strict definition of the clinical and
      endoscopic findings of patients experiencing complete clinical response after
      neoadjuvant chemoradiation therapy may provide a useful tool for the
      understanding of outcomes of patients managed with no immediate surgery allowing
      standardization of classifications and comparison between the experiences of
      different institutions.

PMID- 21178867
TI  - Diverticulitis in transplant patients and patients on chronic corticosteroid
      therapy: a systematic review.
AB  - BACKGROUND: The clinical course of diverticular disease in immunosuppressed
      patients is widely believed to be more severe than in the general population. In
      this study we systematically reviewed the literature regarding the epidemiology
      and clinical course of diverticulitis in immunosuppressed patients. Our goal was
      to develop recommendations regarding the care of this group of patients. METHODS:
      Using PubMed and Web of Knowledge we systematically reviewed all studies
      published between 1970 and 2009 that analyzed the epidemiology, clinical
      manifestation, or outcomes of treatment of diverticulitis in immunosuppressed
      patients. Keywords of "transplantation," "corticosteroid," "HIV," "AIDS," and
      "chemotherapy" were used. RESULTS: Twenty-five studies met our inclusion
      criteria. All of these studies focused on the impact of diverticulitis in
      patients with transplants or on chronic corticosteroid therapy. The reported
      incidence of acute diverticulitis in these patients was approximately 1%
      (variable follow-up periods). Among patients with known diverticular disease the
      incidence was 8%. Mortality from acute diverticulitis in these patients was 23%
      when treated surgically and 56% when treated medically. Overall mortality was
      25%. CONCLUSIONS: Our study summarizes evidence that patients with transplants or
      patients on chronic corticosteroid therapy 1) have a rate of acute diverticulitis
      that is higher than the baseline population and 2) a mortality rate with acute
      diverticulitis that is high. Further research is needed to define whether these
      risks constitute a mandate for screening and prophylactic sigmoid colectomy.

PMID- 21178869
TI  - The anal fistula plug as an adjunct to transanal advancement flap repair.

PMID- 21178872
TI  - [Prostate cancer: the importance of tumor mapping].

PMID- 21178873
TI  - [Splenic artery aneurysm: diagnosis and endovascular therapy].
AB  - Splenic artery aneurysms are now diagnosed more frequently thanks to the increase
      and improvement in different imaging techniques. In case of rupture they are
      potentially life threatening and thus in certain cases may require appropriate
      preventive treatment. This treatment should be offered to patients with suspected
      pseudoaneurysms, with an aneurysm larger than 20mm in diameter, or which is
      progressing. The development of interventional endovascular radiology has
      provided new therapeutic options for the management of aneurysms, by excluding
      the sac from the arterial circulation with coil embolisation or with a covered
      stent. The success rate of these treatments is between 75 and 100% with
      significantly less morbidity and mortality than with surgical techniques.

PMID- 21178874
TI  - [Imaging of cranial gunshot traumas].
AB  - Cranial traumas from gunshot wounds are characterised by the impact of a high
      velocity projectile. There are therefore serious, life threatening traumas. CT
      Scan is essential in the emergency setting for initial evaluation of traumatic
      bone and parenchymatous injuries to determine the indication for neurosurgery and
      appropriate medical management. In case of survival, CT Scan and MRI can be used
      to monitor progress and any possible complications, in particular vascular or
      infectious complications which are specific to this type of injury.

PMID- 21178875
TI  - [The role of diffusion 3-Tesla MRI in detecting prostate cancer before needle
      biopsy: multiparametric study of 111 patients].
AB  - AIM: Evaluate diffusion MRI in the multiparametric assessment of prostate cancer
      before needle biopsy. MATERIALS AND METHODS: One hundred eleven patients with
      suspected prostate cancer (mean age: 63 years old, median PSA: 7 ng/mL) were
      examined before undergoing needle biopsy (59 patients with a history of a
      negative biopsy and 52 without a history of biopsy). A diffusion sequence type SS
      SE-EPI (TR/TE: 5357/58, fEPI: 73, b 0 and 1000 s/mm2, axial) with a qualitative
      analysis of the ADC map was performed in addition to T2 and T1 gadolinium
      enhanced sequences on 3 T MRI with an endorectal coil. The histological
      correlations were obtained by ultrasound guided needle biopsy (85 patients) or
      radical prostatectomy (26 patients). RESULTS: The correlation of the results of
      the diffusion sequence in the series of the 111 patients and the biopsies of the
      entire prostate or the hemiprostate had a sensitivity of: 92%, 77%; a specificity
      of: 55%, 70%; a positive predictive value of: 77%, 62%; a negative predictive
      value of: 84%, 80% and an efficacy of 78%, 75% respectively. The agreement of the
      three sequences had a specificity of 84.3%. CONCLUSION: The sensitivity of
      diffusion MRI is high for the detection of cancer of the prostate. Specificity of
      sequences is good. The results of simple visual assessment of the ADC map are
      good.

PMID- 21178876
TI  - [The outcome of children presenting with a prenatally diagnosed arachnoid cyst].
AB  - AIM: Evaluate the outcome of children with prenatally diagnosed arachnoid cysts.
      MATERIAL AND METHODS: Retrospective study of seventeen cases of children who were
      diagnosed with an arachnoid cyst during prenatal MRI between July 1994 and
      January 2007 and followed up for a mean 6 years and 6 months. Follow-up was based
      on evaluation of clinical files and contacts with the physicians who were
      following the children. The children were divided into three groups: group 1
      normal development, group 2: minor clinical signs, normal schooling, group 3:
      major clinical symptoms, schooling disturbed. RESULTS: Eight of the 17 patients
      included in this study underwent derivation surgery for the cyst. Eight of the 17
      children were in group 1, and 3 in group 2. Four of the 6 children in group 3 had
      associated symptoms. Two of the children in group 3 present with a supratentorial
      cyst, and 4 with a cyst of the posterior fossa. CONCLUSION: The prenatal
      diagnosis of a arachnoid cyst should be accompanied by a search for associated
      lesions. The risk of hydroencephalitis should be explained to the parents.

PMID- 21178877
TI  - [Vascular ischemic lesions of the kidney in multiple trauma patients: incidence
      and management, a report of 7 cases].
AB  - AIMS: Study the incidence, type and outcome of traumatic ischemic arterial
      lesions of the kidney in multiple trauma patients. MATERIALS AND METHODS:
      Retrospective study of 500 multiple trauma patients who underwent whole body 64
      slice CT Scan (mean age 34 years old, sex ratio 4M/1W, mean ISS 29). RESULTS:
      There were seven cases of vascular lesions of the left kidney 1.4% of patients
      (men, median age 25 years old, mean ISS43.9). These were closed traumas with
      sudden deceleration and dissection of the renal artery trunk in three cases and
      injury to its branches in four cases with preserved excretion. Three patients
      died of associated injuries, including one patient who received a stent on D0.
      One patient underwent a nephrectomy and the three other patients were not treated
      which did not affect renal function or pressure (follow-up 19 months).
      CONCLUSION: We found a high incidence of traumatic renal dissection in multiple
      trauma patients. Multidetector scan appears to provide the best results for the
      diagnosis of these lesions as well as the many associated lesions resulting in a
      very poor prognosis for these patients. Treatment is not well defined and
      management of these lesions is often of secondary importance because of the
      severity of associated injuries.

PMID- 21178878
TI  - [Magnetic Resonance Imaging for ischemic cholangitis in the presence of
      hereditary hemorrhagic telangiectasia].

PMID- 21178879
TI  - [Paradoxical embolus of the carotid bifurcation].

PMID- 21178880
TI  - [Myometrial and perisigmoid abscess on sigmoiditis: treatment by radiological
      draining].

PMID- 21178881
TI  - [Primary non-Hodgkin's lymphoma of the breast: a case report].

PMID- 21178882
TI  - [Intraosseous epitheloid hemangioma of the femur].

PMID- 21178883
TI  - [A rare tumor: endometrial stromal nodule].

PMID- 21178884
TI  - [Extra-lobar pulmonary sequestration associated with a bronchogenic cyst: a case
      report].

PMID- 21178885
TI  - [Answer September to e-quid. Chondroid chordoma].

PMID- 21178888
TI  - [The issues of radiation protection in medical imaging].

PMID- 21178889
TI  - [Basic concepts of radiology physics].
AB  - An x-ray tube mainly emits low-energy X-rays, with few maximum energy E0 (equal
      in keV to the voltage U in kV) x-rays. Aluminium filtration (mandatory minimum
      thickness of 1.5 to 2.5 mm based on tube voltage) reduces soft X-rays and
      provides a mean energy equal to 2/3 E0. The half value layer of a reference
      material characterizes the spectrum. X-ray attenuation in tissues is due to
      secondary electron interactions: photoelectric effect at low-energy, especially
      in dense materials with high Z number; compton effect at intermediate-energy,
      proportional to density. The optimization of acquisition parameters of a
      medically necessary examination is based on appropriate selection of the highest
      voltage (U in kV) providing the best contrast and lowest tube current (Q in mAs)
      providing a diagnostic image.

PMID- 21178890
TI  - [Concepts of dosimetry].
AB  - The effects of exposure to ionizing radiation are determined by the absorbed dose
      D. The equivalent dose H takes into consideration the variation in probability of
      a stochastic effect (cancer, leukemia, genetic mutation) based on the quality of
      the exposure. The effective dose E takes into account the sensitivity of tissues
      (T) to stochastic effects from radiation exposure. Optimization of radiation
      exposure to patients in diagnostic radiology in based on diagnostic reference
      levels (DRL): entrance surface dose or dose-area product for conventional
      radiology; CT dose index and DLP for CT.

PMID- 21178891
TI  - [Typical patient radiation doses in diagnostic imaging].
AB  - Radiologists should be able to appreciate the radiation dose delivered to
      patients for routine diagnostic procedures. The radiology report should include
      data necessary to calculate the patient dose in Gray. Using the effective dose,
      it is possible to compare with other source of radiation exposure. Simple
      formulas, taking into account different anatomical regions, derived from dose
      area product (conventional radiography) or dose-length product (CT) are provided
      to calculate the effective dose in Sievert. For conventional (non-interventional)
      radiography, the effective dose for a given exam is inferior or equal to the
      yearly background radiation. For CT, the effective dose corresponds to 1 to 10
      years of yearly background radiation.

PMID- 21178892
TI  - [The framework of radiation protection in France].
AB  - Over the last 10 years, the framework of radiation protection in France has
      undergone significant modifications. This has mainly been the result of
      implementation of European directives, which are based on new data and evolving
      concepts at the international level. As a practical matter, public health laws
      and labor laws have evolved to strengthen the radiation protection to both
      patients and workers. For patients, the indication for the examination must be
      better justified and the exposure should be optimized and recorded. For workers,
      the maximum exposure limits have been reduced while monitoring and risk
      assessment have been reinforced. In addition, the equipment is subject to
      additional quality control evaluations while the facilities are assessed for
      safety.

PMID- 21178893
TI  - [The radiologist's responsibilities for the radiation protection of patients].
AB  - The obligations of the radiologist for the radiation protection of patients
      include a review of the appropriateness of the examination and optimization of
      the protocol. Both internal and external quality assurance programs are
      mandatory. The specific tasks and their frequency are defined by the AFSSAPS. The
      radiology report of procedures performed over radiosensitive regions must include
      the delivered dose. The imaging technique must be optimized based on published
      guidelines or law for the most frequent examinations. All radiologists should be
      familiar with radiation protection. Incidents should be reported to the Nuclear
      Safety Authority.

PMID- 21178894
TI  - [Duties of the radiologist for the radiation protection of radiation workers].
AB  - After a risk analysis has been completed by the radiation safety officer, all
      entities where a source of ionizing radiation is present must established a
      monitored or controlled zone containing the source. When exposure exceeds the
      maximum regulatory dose, a dedicated color-coded controlled (yellow or orange) or
      restricted zone must be established. All assessments performed by the RSO should
      reflect normal working conditions. From these results, workers can be divided
      into two categories, A or B, based on their level of exposure. The workers should
      undergo medical and dosimetric follow-up with the use of passive dosimetry. The
      use of operational dosimetry should be added when working in a controlled zone. A
      radiation dosimetry report for each worker should be available to the
      occupational medicine provider to ensure appropriate dosimetric monitoring.

PMID- 21178895
TI  - [Dose reduction during CT coronary angiography].
AB  - Dose delivery during CT coronary angiography with retrospective ECG gating is
      high especially due to the important slice overlapping. Optimization of the
      acquisition parameters is necessary to reduce patient exposure. First, the height
      of the scan field should be limited to the heart. Both kV and mA should be
      adjusted based on patient morphology. ECG gated exposure modulation with mA
      reduction during systole, a technique most applicable for patients with slow and
      regular heart rate, can result in a dose reduction up to 50%. The use of
      prospective ECG gating can also reduce patient dose. This technique also requires
      patients with slow and regular heart rate.

PMID- 21178896
TI  - [Technical parameters to decrease the radiation dose from conventional and
      digital radiographs].
AB  - Reducing radiation dose while maintaining adequate image quality on conventional
      and digital radiographs requires optimal use of the unit. Additional filtration
      avoids unnecessary tissue exposure and improves photon transmission. Automatic
      exposure control may reduce exposure and dose. The volume of tissue imaged must
      be limited by the use of diaphragms and shutters or compression. Sensitive
      detectors with increased photon detection also contribute to reduce dose.
      Radiographic films combined to rare-earth screens also afford a good photon
      conversion efficiency. Large area flat panel amorphous silicon x-ray sensors may
      also reduce dose up to 50% compared to films. Finally, calculation of the Kerma
      area product independent of the source distance constitutes an important
      indicator of radiation dose.

PMID- 21178897
TI  - [Radiation protection of patients in interventional radiology].
AB  - The purpose of this article is to provide radiologists with key elements of
      radiation protection for interventional radiology patients. The following points
      will be discussed: standards of the fluoroscopy units, dedicated dosimetry, risks
      (especially cutaneous) and means to reduce them, optimization of interventional
      radiology dose protocols, and national and international regulations.
      Appropriateness criteria in interventional radiology are national guidelines that
      should be implemented.

PMID- 21178898
TI  - [Radiation protection for technologists and radiologists in interventional
      radiology].

PMID- 21178899
TI  - Application of cycloaddition reactions to the syntheses of novel boron compounds.
AB  - This review covers the application of cycloaddition reactions in forming the
      boron-containing compounds such as symmetric star-shaped boron-enriched dendritic
      molecules, nano-structured boron materials and aromatic boronic esters. The
      resulting boron compounds are potentially important reagents for both materials
      science and medical applications such as in boron neutron capture therapy (BNCT)
      in cancer treatment and as drug delivery agents and synthetic intermediates for
      carbon-carbon cross-coupling reactions. In addition, the use of boron cage
      compounds in a number of cycloaddition reactions to synthesize unique aromatic
      species will be reviewed briefly.

PMID- 21178900
TI  - Seasonal variation in total phenolic and flavonoid contents and DPPH scavenging
      activity of Bellis perennis L. flowers.
AB  - Variations in total phenolic and flavonoid contents as well as antioxidant
      activity of Bellis perennis (common daisy) flowers were investigated. The flowers
      were collected monthly (from March to October, i.e., during the usual flowering
      season of the plant) at three localities in three different years. Total
      flavonoids were determined spectrophotometrically by two methods: by formation of
      a complex with aluminium chloride after acidic hydrolysis of flower extracts
      (method 1) and by reaction with boric and oxalic acids in extracts without their
      modification (method 2). Total phenolics were determined spectrophotometrically
      using the Folin-Ciocalteu reagent. The antioxidant activity was determined
      spectrophotometrically by a 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical
      scavenging assay. The contents of flavonoids varied from 0.31 to 0.44 mg
      quercetin equivalent/100 mg dry weight (method 1) and from 1.37 to 2.20 mg
      pigenin-7-glucoside equivalent/100 mg dry weight (method 2). Total phenolics
      ranged from 2.81 to 3.57 mg gallic acid equivalent/100 mg dry weight. The
      antioxidant activity expressed as IC(50) values varied from 66.03 to 89.27 ug/mL;
      it is about 50, 30, 20, and 10 times lower as compared with quercetin, ascorbic
      acid, Trolox(r), and butylhydroxytoluene, respectively, and about five times
      higher in comparison with apigenin-7-glucoside. There is a significant
      correlation between antioxidant activity and total phenolics. No correlation
      between total flavonoid contents and antioxidant activity was observed. Contents
      of phenolics and flavonoids as well as antioxidant activity of daisy flowers vary
      to a relatively small extent during the year and are not dependant on the time of
      collection. Thus, the flowers possess comparable quality as to these
      characteristics over the whole flowering season of Bellis perennis. Effects of
      environmental factors on the amounts of secondary metabolites in plants are also
      discussed.

PMID- 21178901
TI  - Aristolactams and Alkamides of Aristolochia gigantea.
AB  - A new aristolactam, aristolactam 9-O-beta-D-glucopyranosyl-(1->2)-beta-D
      glucoside, and two alkamides, N-cis- and N-trans-p-coumaroyl-3-O-methyldopamine,
      were isolated from stems of Aristolochia gigantea, together with the known
      compounds allantoin, E-nerolidol, beta-sitosterol, (+)-kobusin, (+)-eudesmin,
      trans-N-feruloyltyramine, trans-N-coumaroyltyramine, trans-N-feruloyl-3-O
      methyldopamine, aristolactam Ia-N-beta-D-glucoside, aristolactam Ia 8-beta-D
      glucoside, aristolactam IIIa, and magnoflorine. Their structures were determined
      by spectroscopic analyses.

PMID- 21178902
TI  - A general synthetic procedure for 2-chloromethyl-4(3H)-quinazolinone derivatives
      and their utilization in the preparation of novel anticancer agents with 4
      anilinoquinazoline scaffolds.
AB  - In our ongoing research on novel anticancer agents with 4-anilinoquinazoline
      scaffolds, a series of novel 2-chloromethyl-4(3H)-quinazolinones were needed as
      key intermediates. An improved one-step synthesis of 2-chloromethyl-4(3H)
      quinazolinones utilizing o-anthranilic acids as starting materials was described.
      Based on it, 2-hydroxy-methyl-4(3H)-quinazolinones were conveniently prepared in
      one pot. Moreover, two novel 4-anilinoquinazoline derivatives substituted with
      chloromethyl groups at the 2-position were synthesized and showed promising
      anticancer activity in vitro.

PMID- 21178903
TI  - Efficient Lewis acid ionic liquid-catalyzed synthesis of the key intermediate of
      coenzyme Q10 under microwave irradiation.
AB  - An efficient synthesis of a valuable intermediate of coenzyme Q(10) by microwave
      assisted Lewis acidic ionic liquid (IL)-catalyzed Friedel-Crafts alkylation is
      reported. The acidity of six [Etpy]BF(4)-based ionic liquids was characterized by
      means of the FT-IR technique using acetonitrile as a molecular probe. The
      catalytic activities of these ionic liquids were correlated with their Lewis
      acidity. With increasing Lewis acid strength of the ionic liquids, their
      catalytic activity in the Friedel-Crafts reaction increased, except for
      [Etpy]BF(4)-AlCl(3). The effects of the reaction system, the molar fraction of
      Lewis acid in the Lewis acid ILs and heating techniques were also investigated.
      Among the six Lewis acid ionic liquids tested [Etpy]BF(4)-ZnCl(2) showed the best
      catalytic activity, with a yield of 89% after a very short reaction time (150
      seconds). This procedure has the advantages of higher efficiency, better
      reusability of ILs, energy conservation and eco-friendliness. The method has
      practical value for preparation of CoQ(10) on an industrial scale.

PMID- 21178904
TI  - Does esophageal dysfunction affect the course of treadmill stress test in
      patients with recurrent angina-like chest pain?
AB  - INTRODUCTION: cardioesophageal reflex may increase severity of chest pain and
      signs of myocardial ischemia on electrocardiogram (ECG), both in patients with
      and without significant coronary artery stenosis. OBJECTIVES: the aim of the
      study was to evaluate the relationships between esophageal pH and pressure and
      clinical and electrocardiographic signs of myocardial ischemia. PATIENTS AND
      METHODS: in 129 consecutive patients with recurrent chest pain, 77 without
      significant coronary artery lesions in coronary angiography and 52 with
      myocardial ischemia, panendoscopy, pH-metry, manometry, and treadmill stress test
      were performed. RESULTS: The prevalence of esophageal disorders was similar in
      patients with and without significant coronary artery narrowing. Subjects with
      significant ST interval depression in the stress test had a higher rate of
      simultaneous esophageal contractions. There were no differences in the results of
      the treadmill test between patients with and without esophageal disorders. Forty
      percent of patients with significant coronary artery lesions, who had to stop the
      test because of chest pain, did not present significant ST interval depression on
      ECG; however, such depression was observed in 60% of patients with normal
      coronary angiography. Patients with exercise-provoked chest pain had more
      pronounced abnormalities in esophageal pH, together with the amplitude and
      coordination of esophageal contractions. Demographic and clinical factors
      associated with chest pain and changes in exercise ECG were not evaluated.
      CONCLUSIONS: esophageal disorders are an important cause of chest pain,
      potentially affecting the results of the treadmill stress test. However, further
      research is needed to determine the predictors of the cardioesophageal loop
      activity.

PMID- 21178905
TI  - C-reactive protein and chronic hepatitis C virus infection in diabetic patients.
AB  - INTRODUCTION: C-reactive protein (CRP) is one of the most widely used risk
      markers of cardiovascular disease in clinical practice. The contribution of
      hepatitis C virus (HCV) infection to low-grade inflammation in diabetic patients
      and its significance for cardiovascular risk scoring remain unclear. OBJECTIVES:
      The aim of the study was to investigate the relationship between HCV infection
      and CRP levels as one of the markers of cardiovascular risk in diabetic patients.
      PATIENTS AND METHODS: we compared patients with HCV infection and diabetes (n =
      46) with HCV-negative type 1 (n = 56) or type 2 diabetic patients (n = 54), as
      well as HCV patients without diabetes (n = 54). RESULTS: CRP levels in diabetic
      HCV patients were lower than in type 2 diabetic patients (P <0.001), similar to
      those in the type 1 diabetic group (P = 0.747), and higher than in nondiabetic
      HCV subjects (P = 0.002). The median values were 1.07, 2.58, 0.91, and 0.45 mg/l,
      respectively. White blood cell count in diabetic HCV subjects was lower than in
      those with type 2 diabetes (P = 0.029) and similar to that found in type 1
      diabetic (P = 0.064) and nondiabetic HCV patients (P = 0.279). There was
      difference in erythrocyte sedimentation rate between diabetic and nondiabetic HCV
      groups (P = 0.025); the respective medians were 10 and 5 mm/h. CONCLUSIONS: these
      findings indicate that HCV hepatitis may modulate chronic inflammatory state in
      diabetic patients. Moreover, these results suggest that screening for HCV should
      be considered prior to assessment of cardiovascular risk in diabetic patients,
      because the results may affect the cardiovascular risk scoring.

PMID- 21178906
TI  - Management of cardiac electrical implantable devices in patients nearing the end
      of life or requesting withdrawal of therapy: review of the Heart Rhythm Society
      2010 consensus statement.
AB  - Cardiac implantable electrical devices (CIEDs) are increasingly common
      interventions for a wide spectrum of cardiovascular diseases. Caring for patients
      with life-sustaining devices such as CIEDs at the end of life raises legal and
      ethical challenges. In 2010, the Heart Rhythm Society (HRS) published an expert
      consensus statement to review the principles and practice of CIED deactivation.
      This statement addressed a wide range of ethical and legal principles while
      providing guidance for communication, decision-making, and procedures in a
      variety of settings. In this article, we provide a summary of the HRS guidelines
      and highlight the most important features of CIED deactivation for the practicing
      clinician.

PMID- 21178907
TI  - European guidelines for the management of malignant pleural mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is nearly invariably lethal tumor of the
      pleura. Significant therapeutic nihilism exists among health professionals.
      Recent progress has reshaped the clinical landscape in the treatment of MPM. Two
      European guidelines have been published, one from the task force of the European
      Respiratory Society and the European Society of Thoracic Surgery, and the other
      from the European Society of Medical Oncology. With these guidelines and
      recommendations as a guidepost, this review discusses the major changes and their
      impact on the management of MPM.

PMID- 21178908
TI  - Global guidelines for asthma management: summary of the current status and future
      challenges.
AB  - The Global Initiative for Asthma (GINA) is an initiative started in the early
      1990s to develop guidelines for asthma diagnosis and management that were
      applicable to both developed and developing countries. GINA now recommends that
      achieving overall asthma control is the goal of therapy. Overall asthma control
      consists of 2 domains: to achieve day-to-day (or current) asthma control and to
      minimize future risk measured by the absence of asthma exacerbations, the
      prevention of accelerated decline in lung function over time, and no side effects
      from medications. The GINA treatment paradigm consists of 5 treatment steps. At
      each step a preferred option and other alternatives are identified. Step 1 is as
      needed (prn) rapid-acting inhaled beta2-agonist. The other 4 treatment steps
      include a controller option, ranging from low-dose inhaled corticosteroids (ICSs)
      as the preferred treatment option at Step 2, to high-dose ICSs plus long-acting
      inhaled beta2-agonist combinations together with oral corticosteroids at Step 5.
      Once the level of asthma control has been established, consideration should be
      given to reducing the amount of treatment. By contrast, if asthma is
      uncontrolled, treatment needs to be increased to the next step. In an effort to
      remain current, a yearly update, based on an extensive review of the previous
      year's peer-reviewed literature on asthma management, is available on the web
      version of the GINA guidelines.

PMID- 21178909
TI  - Electrical impedance tomography to guide ventilation in ALI-ARDS patients: a
      research tool for zealous physiologists or an imminent support for the real world
      intensivist?

PMID- 21178910
TI  - Extracorporeal membrane oxygenation in H1N1 pandemic: a double edged sword.

PMID- 21178911
TI  - A comparison of spinal anesthesia with low-dose hyperbaric levobupivacaine and
      hyperbaric bupivacaine for transurethral surgery: a randomized controlled trial.
AB  - BACKGROUND: The aim of this study was to compare spinal anesthesia effects of low
      dose hyperbaric levobupivacaine and low-dose hyperbaric bupivacaine for
      transurethral procedures. METHODS: In this double-blind, randomized, controlled
      study, a total of 60 patients who were ASA I-III were randomized into two groups.
      Group B received 7.5 mg hyperbaric bupivacaine plus 25 ug fentanyl, and Group L
      received 7.5 mg hyperbaric levobupivacaine plus 25 ug fentanyl intrathecally. The
      onset time to T10 dermatome, times to maximum sensory and motor block levels,
      time to two-segment regression of sensory block, time to Bromage score zero, time
      to full recovery of sensory block, and hemodynamic values, as well as adverse
      effects, were recorded. The primary outcome was the time to complete regression
      of motor block. RESULTS: The onset time of block to T10, time to maximum sensory
      block, and time to two-segment regression were similar in both groups. The time
      to maximum motor block was shorter in Group B (7 +/- 3 min) than in Group L (12+/
      5 min), (P<0.001). The time to a Bromage score of zero (recovery of motor block)
      was shorter in Group L (105+/-19 min) than in Group B (113+/-7 min), (P=0.04).
      The time to full recovery of sensory block was shorter in Group B (127+/-14 min)
      than in Group L (157+/-34 min), (P<0.001). The requirement for analgesia was
      earlier in Group B (305+/-50 min) than in Group L (389+/-146 min), (P=0.004).
      CONCLUSION: Although both techniques provide adequate spinal block and have few
      similar side effects for transurethral surgery, the use of low-dose hyperbaric
      levobupivacaine plus fentanyl may be preferable to low-dose hyperbaric
      bupivacaine plus fentanyl because of the reduced motor block, shorter duration of
      motor block, longer duration of sensory block and longer time to the first
      requirement for analgesia.

PMID- 21178912
TI  - Regional intratidal gas distribution in acute lung injury and acute respiratory
      distress syndrome assessed by electric impedance tomography.
AB  - BACKGROUND: Regional tidal volume distribution and end-expiratory lung volume
      (EELV) distribution in patients with acute lung injury and acute respiratory
      distress syndrome (ALI, ARDS) have previously been investigated using computed
      tomograpy and electric impedance tomography (EIT). In the present study, we
      utilized the high temporal resolution of EIT to assess intratidal gas
      distribution. METHODS: Sixteen ventilator patients with ALI/ARDS were studied.
      EIT was used for analysis of intertidal, intratidal and EELV regional
      distribution. Intratidal regional gas distribution (ITV) was analyzed by dividing
      the regional tidal impedance signal into eight iso-volume parts. Alveolar
      pressure/volume curves during ongoing ventilation and volume-dependent compliance
      during the initial inspiration (Cini) were calculated. A low-pressure (~32 cm
      H2O) recruitment maneuver and a decremental PEEPtrial were implemented. RESULTS:
      The increase in EELV was preferentially distributed to non-dependent lung
      regions. The intratidal gas distribution pattern was similar to the tidal volume
      distribution following increased PEEP; non-dependent distribution decreased and
      dependent distribution increased during inspiration. Cini increased, indicating
      successful recruitment. The distribution varied widely among individual patients.
      In one patient with a low EELV, the ITV pattern showed that non-dependent
      distribution increased and dependent distribution decreased. This coincided with
      minimal improvement in volume-dependent compliance. This patient probably needed
      higher recruitment pressure. In one patient with a high baseline EELV, there was
      very little change in regional ITV, and non-dependent Cini decreased. This was
      probably a patient with low potential recruitability, who required only moderate
      PEEP. CONCLUSION: On-line intratidal gas distribution monitoring offers
      additional information on recruitability and optimal PEEP.

PMID- 21178913
TI  - Extracorporeal membrane oxygenation for pandemic H1N1 2009 respiratory failure.
AB  - BACKGROUND: Severe respiratory failure related to infection with the pandemic
      influenza A/H1N1 2009 virus is uncommon but possibly life-threatening. If, in
      spite of maximal conventional critical care, the patient's condition
      deteriorates, extracorporeal membrane oxygenation (ECMO) may be a life-saving
      procedure. METHODS: An observational study approved by the local ethics committee
      was carried out. Data from all patients treated with ECMO at the ECMO Center
      Karolinska for influenza A/H1N1 2009-related severe respiratory failure were
      analyzed. The main outcome measure was survival three months after discharge from
      our department. RESULTS: Between July 2009 and January 2010, 13 patients with
      H1N1 2009 respiratory failure were treated with ECMO. Twelve patients were
      cannulated for veno-venous ECMO at the referring hospital and transported to
      Stockholm. One patient was cannulated in our hospital for veno-arterial support.
      The median ratio of the arterial partial oxygen pressure to the fraction of
      inspired oxygen (P/F ratio: PaO2 /FiO2) before cannulation was 52.5
      (interquartile range 38-60). Four patients were converted from veno-venous to
      veno-arterial ECMO because of right heart failure (three) or life-threatening
      cardiac arrhythmias (one). The median maximum oxygen consumption via ECMO was 251
      ml/min (187-281 ml/min). Twelve patients were still alive three months after
      discharge; one patient died four days after discharge due to intracranial
      hemorrhage. CONCLUSION: Patients treated with veno-venous or veno-arterial ECMO
      for H1N1 2009-related respiratory failure may have a favorable outcome.
      Contributing factors may include the possibility of transport on ECMO, conversion
      from veno-venous (v-v) or veno-arterial (v-a) ECMO if necessary, high-flow ECMO
      to meet oxygen requirements and active surgery when needed.

PMID- 21178914
TI  - Traumatic brain injury in pediatric patients.
AB  - Traumatic brain injury (TBI) in children is frequent, sometimes lethal, and may
      have life-long consequences in survivors. Prevention at school and in sports,
      including both kids and families, is of paramount importance. Scarce data are
      available in terms of epidemiology, physiopathology, management and prognosis.
      This non-systematic review suggests that rational organization of rescue and
      transport to designated hospitals, linked with early diagnosis/removal of
      surgical masses and comprehensive monitoring and intensive care, offer the best
      chances for reducing mortality and morbidity in severe cases. After the acute
      phase rehabilitation and families play a fundamental role.

PMID- 21178916
TI  - Genetics of premature ovarian failure.
AB  - Premature ovarian failure (POF) is defined as a primary ovarian insufficiency
      before the age of 40 years. It is characterized by a cessation of menstruation
      for at least 4 months associated with the elevation of serum follicle-stimulating
      hormone (FSH) concentration (FSH>40 IU/L). It affects approximately 1% of women
      under 40. Known causes of premature ovarian failure can be classified as genetic,
      autoimmune, environmental, iatrogenic (after chemotherapy, radiations, surgery)
      and idiopathic. It is estimated that up to 40% of POF can be attributed to
      genetic causes. Classification of genetic causes can be different. We present
      here review of genetic causes of POF based on classification : non-syndromic POF
      and syndromic causes of POF. The list of the candidate genes related to POF is
      still increasing. Elucidation of genetic determination of POF has a critical
      significance for identification the possible marker of POF or possible new kind
      of POF therapy.

PMID- 21178915
TI  - Local anesthetic toxicity in interscalene block: clinical series.
AB  - We experienced two cases of local anesthetic toxicity by interscalene block. A 62
      year-old man received interscalene block with lidocaine 1% 30 mL and bupivacaine
      0.25% 20 mL under light sedation followed by general anesthesia. He was not awake
      at one hour after surgery with his pupils dilated. Three hours after interscalene
      block, he became awake with no complication. A 73-year-old female received
      interscalene block with lidocaine 1% 15 mL and ropivacaine 0.75% 15 mL under
      light sedation. After the injection, a catheter was inserted 5 cm. About 7-8 min
      after catheter insertion, generalized tonic seizure occurred. Seizure stopped in
      two min after anesthesia induction. She had no complication after surgery. These
      two cases showed neurological toxicity by interscalene block with lidocaine and
      bupivacaine or with ropivacaine without hemodynamic complication.

PMID- 21178917
TI  - Infertility and pregnancy in women with polycystic ovary syndrome.
AB  - Management of polycystic ovary syndrome (PCOS) usually spans a woman's
      reproductive years. While treatment of androgenic symptoms is often a primary
      concern, periodically, the regimen has to be modified because of a desire for
      pregnancy. At this time the couple should be evaluated for factors that may
      contribute to infertility and this should include semen analysis. However, for
      many, anovulation is likely to be the cause of infertility and ovulation
      induction is generally required. The premise on which ovulation induction in PCOS
      is based is two-fold: increasing ovarian exposure to follicle stimulating hormone
      (FSH) and/or correcting hormonal derangements. Potential differences in
      pathogenesis, evidenced clinically by phenotypic diversity, would suggest that
      treatment should be individualized. After a brief overview of factors relating to
      infertility, this paper outlines treatments available for ovulation induction in
      women with PCOS and provides a critical appraisal of management options. These
      options include the use of clomiphene citrate, insulin sensitizers, and the
      combination. Protocols for ovulation induction with FSH injections are outlined
      and the relative risks of multiple gestation and severe ovarian hyperstimulation
      syndrome of these various protocols discussed. The use of aromatase inhibitors
      and the occasional use of glucocorticoids are briefly reviewed, and indications
      for in vitro fertilization and laparoscopic ovarian diathermy outlined. Pregnancy
      outcome in this patient population is also discussed.

PMID- 21178918
TI  - The future trends of induction of ovulation.
AB  - The aim of this paper was to discuss future trends of induction of ovulation in
      women with ovulatory disorders who are not trying to intentionally make multiple
      follicles for the purpose of in vitro fertilization. Modern methods of correcting
      ovulatory disorders are compared historically to older techniques. Older
      techniques include the use of the selective estrogen receptor modulators, e.g.,
      clomiphene citrate and relatively impure gonadotropin preparations, e.g., human
      menopausal gonadotropins. The "newer" drugs include other ways to temporarily
      lower estrogen to induce a rise in endogenous gonadotropin, e.g., aromatase
      inhibitors. Though purported to have less adverse effect on endometrial thickness
      and/or cervical mucus no clear-cut advantages have emerged. Though there was
      promise that higher pregnancy rates would be obtained by replacing impure
      gonadotropins with either all follicle stimulating hormone (FSH) products
      especially recombinant FSH if anything there is a trend to add luteinizing
      hormone (LH) back. New drugs are merely more convenient, i.e., present
      subcutaneous vs. intramuscular injection with trends for less frequent
      injections. New trends include more emphasis on maximizing efficacy of follicle
      maturing drugs, e.g., luteal phase support with progesterone, and carefully
      striving to find techniques to avoid over stimulation. Multiple gestations are
      much less tolerated today than yesterday. Cumulative evidence suggests diminished
      oocyte reserve does not indicate diminished oocyte quality and pregnancy can be
      achieved by consideration of the biologically adverse effect of elevated serum
      FSH on FSH receptors.

PMID- 21178919
TI  - Assisted reproductive technology and ovarian cancer.
AB  - Ovarian cancer has the highest mortality among all gynaecological cancers, being
      multiparity and oral contraceptive use the most important protective factors.
      According to both the "incessant ovulation" and "increased gonadotrophin"
      theories, fertility drugs might have an association with the development of
      ovarian cancer, as has been reported by some studies. However, infertility and
      nulliparity may act as confounding factors and most studies regarding this issue
      are hampered by methodological limitations. It seems that female infertility may
      be associated with a modest increase in ovarian cancer risk in those patients who
      remain nulligravid despite long periods of unprotected intercourse. Globally,
      most studies are reassuring in not showing a link between the use of fertility
      drugs and an increased risk of ovarian cancer. Nonetheless, further research in
      well-designed studies is warranted.

PMID- 21178920
TI  - Measuring ovarian function in young cancer survivors.
AB  - It is known that young female cancer survivors are at higher risk for decreased
      fertility and early menopause. Because the risk of these outcomes varies by age,
      cancer type, treatment regimen and other patient-specific characteristics, there
      is a need for valid tools for measuring and predicting reproductive function in
      this population. Ovarian reserve tests (ORT) include serum and ultrasound
      biomarkers used in characterizing healthy ovarian aging and predicting ovarian
      reserve prior to fertility treatment. This review summarizes efforts to translate
      ORT to use in female cancer patients. To date, small longitudinal and cross
      sectional studies of young cancer patients demonstrate that gonadotoxic
      chemotherapy impact ORT. While follicle stimulating hormone (FSH), anti-Mullerian
      hormone (AMH), inhibin B, antral follicle count (AFC) and ovarian volume have all
      been demonstrated to change with exposure to gonadotoxic therapy, FSH, AMH and
      AFC appear to be the most sensitive. More data are needed to determine the long
      term effect of hormonal agents from tamoxifen to GnRH agonists on ORT. The effect
      of unilateral oophorectomy acutely or in the long-term on ORT is not known. There
      are some early data postulating that cancer itself may impair ovarian reserve.
      Among cancer survivors, ORT correlate with amenorrhea. Even in young survivors
      with normal menstrual cycles, hormone and ultrasound measures of ovarian reserve
      suggest decreased underlying ovarian reserve than age-matched healthy women. More
      studies are needed to determine the optimal time to test ORT in the large number
      of young survivors on combined estrogen and progesterone contraceptives. A
      significant utility of ORT would be to be able to predict fertility for young
      survivors, and there are no data on this outcome to date. The goal of future
      studies of ORT in young girls and women with cancer is to determine their utility
      as surrogate measures of ovarian function or predictors of infertility or ovarian
      failure. To do so, large-scale data need to be collected through cooperative
      group mechanisms. Epidemiologically, studies need to move from association
      studies to develop ORT into appropriate screening and predictive tests.

PMID- 21178922
TI  - Normal weight men and women overestimate exercise energy expenditure.
AB  - AIM: The limited potential of exercise to induce weight loss could be partly due
      to the overestimation of the energy cost of exercise. The objectives of this
      study were twofold: 1) to investigate whether men and women are able to
      accurately estimate exercise energy expenditure (EE); and 2) to determine whether
      they have the ability to accurately compensate for the EE of exercise during a
      buffet-type meal. METHODS: Sixteen (8 men, 8 women) moderately active (VO2
      peak=45.4+/-7.7 mL.kg-1.min-1), normal weight (BMI=22.8+/-3.3 kg/m2) individuals,
      aged 20-35 years, were studied. They were blinded to two randomly assigned
      experimental conditions: a 200 and a 300 kcal (measured by indirect calorimetry)
      exercise sessions that were performed on a treadmill at the same intensity (50%
      of VO2 peak). At the end of each exercise session individuals were asked to
      estimate EE of the exercise sessions and to then eat the caloric equivalent of
      their estimated exercise EE from a buffet-type meal. RESULTS: Estimated EE was
      higher than measured EE for both the 200 kcal (825.0+/-1061.8 vs. 200.1+/-0.7
      kcal, P<0.05) and 300 kcal (896.9+/-952.4 vs. 300.2+/-0.7 kcal, P<0.05) sessions.
      Further, post-exercise energy intake was higher than measured EE for the 200 kcal
      (556.8+/-204.4 vs. 200.1+/-0.7 kcal, P<0.001) and the 300 kcal (607.2+/-166.5 vs.
      300.2+/-0.7 kcal, P<0.001) sessions. Although post-exercise energy intake was
      lower than estimated EE, no significant differences were noted. CONCLUSION: These
      results suggest that normal weight individuals overestimate EE during exercise by
      3-4 folds. Further, when asked to precisely compensate for exercise EE with food
      intake, the resulting energy intake is still 2 to 3 folds greater than the
      measured EE of exercise.

PMID- 21178921
TI  - Sex hormone-binding globulin genetic variation: associations with type 2 diabetes
      mellitus and polycystic ovary syndrome.
AB  - Sex hormone-binding globulin (SHBG) is the primary plasma transport protein for
      sex steroid hormones and regulates the bioavailability of these hormones to
      target tissues. The gene encoding SHBG is complex and any of several
      polymorphisms in SHBG have been associated with alterations in circulating SHBG
      levels. Epidemiological studies have revealed that low plasma SHBG levels are an
      early indicator of insulin resistance and predict the development of type 2
      diabetes mellitus (T2DM) in both men and women. Although associations between low
      SHBG levels and risk of diabetes could be explained by the observation that
      elevations in insulin suppress hepatic SHBG production, recent studies
      documenting that the transmission of SHBG-altering polymorphisms are associated
      with risk of T2DM suggest that SHBG may have a more direct physiologic role in
      glucose homeostasis. However, the exact mechanism(s) underlying this association
      is not known. Non-diabetic women with the polycystic ovary syndrome (PCOS), a
      common endocrine disorder that is associated with insulin resistance, similarly
      demonstrate lower levels of SHBG. In light of studies investigating polymorphisms
      in SHBG and T2DM, our group and others have hypothesized that SHBG may represent
      a candidate gene for PCOS. In this manuscript, we review studies investigating
      the association between SHBG polymorphisms and PCOS. In summary, multiple studies
      in women with PCOS confirm that certain genetic polymorphisms are associated with
      circulating SHBG levels, but they are not consistently associated with PCOS per
      se.

PMID- 21178923
TI  - Accuracy of polar F6 in estimating the energy cost of aerobic dance bench
      stepping in college-age females.
AB  - AIM: This study: 1) examined the accuracy of the Polar F6 for estimating energy
      expenditure (EE) in a sample of college-age women during aerobic dance bench
      stepping (ADBS) using predicted maximal oxygen consumption (VO2max) and maximal
      heart rate (HRmax), and 2) determined whether the use of actual measures of
      VO2max and HRmax improves the accuracy of the Polar F6 for estimating EE.
      METHODS: Thirty-two females had their VO2max and HRmax predicted by the Polar F6
      heart rate monitor (HRM), and then performed a graded maximal exercise treadmill
      test to determine their actual VO2max and HRmax. The participants then followed a
      20-min ADBS routine while stepping up and down off of a 15.24-cm bench at a
      cadence of 126 beats.min-1. During ADBS, the participants wore two F6 HRM that
      simultaneously collected data. To estimate EE, one HRM utilized their predicted
      VO2max and HRmax (PHRM) while the other HRM utilized their actual VO2max and
      HRmax (AHRM). RESULTS: The predicted HRmax significantly overestimated actual
      HRmax by 3.75 beats.min-1 on average, and the predicted VO2max overestimated
      actual VO2max by 2.63 ml.kg-1.min-1 on average (P<0.01). However, there were no
      significant differences between the PHRM and AHRM (P>=0.05). When compared to
      indirect calorimetry, the PHRM and AHRM significantly overestimated average EE by
      28% (2.4 kcal.min-1) and 27% (2.0 kcal.min-1), respectively (P<0.05).
      CONCLUSIONS: Even when using actual measures of VO2max and HRmax, the Polar F6 is
      inaccurate in estimating EE during ADBS for college-age females.

PMID- 21178924
TI  - Aerobic capacity of male professional futsal players.
AB  - AIM: The aim of this study was to evaluate the aerobic capacity of male
      professional futsal players. METHODS: A total of 186 players (22 goalkeepers and
      164 on-court players) of three Brazilian futsal teams from first division
      performed ergospirometric evaluations (incremental test protocol) in a motorized
      treadmill. Data from maximal oxygen uptake (VO2max) and second ventilatory
      threshold (VT2), as well as speed, heart rate (HR) and BORG scale were presented
      in relation to total of sample and isolated by two main futsal tactical
      positions: goalkeepers and on-court players. RESULTS: The mean values to VO2max
      and VT2 observed in futsal players were respectively 58.00+/-6.37 mL/kg/min and
      51.25+/-5.84 mL/kg/min. Players reached the VO2max at 96.95+/-4.66% of HRmax and
      the VT2 at 90.07+/-5.02%. Goalkeepers presented higher values (P<0.01) of body
      mass and height than on-court players. On-court players presented higher VO2max
      and VT2 in comparison to goalkeepers, and reached these levels at higher exercise
      levels (speed) than goalkeepers. CONCLUSIONS: We conclude that goalkeepers are
      significantly differents than on-court players regarding aerobic capacity. In
      this perspective, these differences are relevant to coaches when planning aerobic
      training sessions in futsal teams.

PMID- 21178925
TI  - Energy cost and efficiency of ski mountaineering. A laboratory study.
AB  - AIM: The purpose of this study is to estimate the energy cost of ski
      mountaineering at different speeds under laboratory conditions. METHODS: By using
      roller skis on a motorized treadmill we have estimated the energy cost and
      biomechanics parameters of ski mountaineering as a function of climbing speed at
      the gradient of 21%. RESULTS: The metabolic energy spent for unit mass and
      distance, C, shows a broad minimum of about 10.6+/-0.2 J kg-1m-1 at roughly 3.5
      km h-1. In addition we find a size-dependent effect: tall subjects spend less
      metabolic energy for unit mass and distance than small subjects at the same
      speed. CONCLUSION: The value of C measured in laboratory agrees with that
      obtained in the field at the preferred speed. This shows that skiers self select
      a speed that minimizes their metabolic cost. The dependence of C on the subject's
      size is explained by a simple model of the skier's dynamics. In addition we have
      calculated the ratio between mechanical work and metabolic energy, which may give
      some hints on the efficiency as a function of the speed. It turns out that
      efficiency increases with the speed up to a maximum located at around 4.5 km/h.

PMID- 21178926
TI  - Effects of the different frequencies of whole-body vibration during the recovery
      phase after exhaustive exercise.
AB  - AIM: This study was to investigate the effects of vibration exercise on the
      oxygen consumption (VO2) and heart rate variability (HRV) during the recovery
      phase after exhaustive exercise. METHODS: Twenty male college students
      volunteered as subjects to participate in the study. The subjects were randomly
      crossover assigned to perform three 10 min vibration exercises, namely non
      vibration (CON, 0 Hz, 0 mm), low-frequency (LFT, 20 Hz, 0.4 mm) and high
      frequency (HFT, 36 Hz, 0.4 mm) treatments immediately after an incremental
      exhaustive cycling exercise in separated days. The beat-to-beat HRV, blood
      lactate concentration and VO2 were measured during the 1-hour recovery phase. The
      time- and frequency-domain indices of HRV were analyzed to confirm the effects of
      vibration exercises on the cardiac autonomic modulation. RESULTS: There were no
      significant differences on the VO2, HRV and blood lactate concentrations at 30th
      minute (post-30 min) or 60th minute (post-60 min) during the recovery phase among
      the three treatments. There were also no significant differences on the excess
      post-exercise oxygen consumption (EPOC) during the recovery phase among the
      treatments. However, the VO2 at post-30 min in CON and LFT were significantly
      higher than the baseline values, whereas the VO2 in HFT returned to resting
      condition at the post-30 min. CONCLUSIONS: The results indicate that both low and
      high frequency vibration exercises could not improve the physiological recovery
      after exhaustive cycling exercise. However, the high frequency vibration exercise
      probably has a potential to facilitate the VO2 to return to the resting level
      during the recovery phase.

PMID- 21178927
TI  - Comparison of the take-off ground reaction force patterns of the pole vault and
      the long jump.
AB  - AIM: The take-off is probably the most important phase of the pole vault. The
      kinematics of pole vault take-off is often described in comparison to the long
      jump take-off. If a kinetic similarity were also evidenced, the extra loading of
      carrying the pole could be avoided by using the long jump style take-off drills
      in pole vault take-off training. However, to our knowledge, a direct comparison
      of the take-off ground reaction force (GRF) pattern of the two types of jump has
      not been reported in the scientific or coaching literature. The purpose of this
      study was to compare the take-off GRF patterns of the support leg in the pole
      vault and the long jump. METHODS: Twelve elite women jumpers undertook pole vault
      and long jump trials. The take-off GRF patterns were recorded by a force plate
      (Kistler-9286AA). Temporal and force parameters were determined for all three GRF
      components. Trials were videotaped to determine the take-off kinematics. Paired
      sample t-tests (SPSS 13.0) were applied (P<=0.05) for comparison between jumps.
      RESULTS: No significant differences were found in kinematics (P>0.05). Overall,
      the GRF patterns were similar, although there were particular significant
      (P<=0.05) differences in contact times, impulses and force peaks. CONCLUSION:
      This study provides scientific support for potential use of the long jump take
      off drills during technical preparation for the pole vault take-off.

PMID- 21178928
TI  - Functional knee brace use by non-injured subjects while performing an anaerobic
      capacity task: preliminary study.
AB  - AIM: The objective of this paper was to investigate if performance was hindered
      in non-injured braced athletes during an anaerobic task. If performance was
      affected, could accommodation to wearing a knee brace occur and thus decreasing
      performance hindrance concern while using a functional knee brace (FKB). METHODS:
      A 2x3 non-braced (NBr) and braced repeated measure factorial design. Five healthy
      athletes completed all testing. Subjects performed the Repeated High Intensity
      Shuttle Test (RHIST) over six days (three days NBr and three days braced).
      Running times were recorded each testing day to determine performance measures
      and percent fatigue levels while using a FKB and if accommodation to FKB use was
      possible. RESULTS: Non significant (F1,4=1.42, P=0.299) faster group mean
      performance time, was recorded for braced subjects relative to the non-braced
      condition. Although relatively faster performance levels were noted during the
      braced testing conditions during days 1 and 3 compared to the non-braced
      condition, these results were also not significant (F2,8=2.82, P=0.118). Lower
      percent fatigue level was recorded during all three braced days compared to non
      braced days. Further, a tendency for accommodation to knee brace trend use was
      noted as the percentage performance difference between the two conditions had
      decreased by the last day of testing. CONCLUSION: Use of a knee brace did not
      hinder performance once accommodation to using the knee brace occurred and
      fatigue was not a factor while using a knee brace. Additional research, using a
      larger sample size and longer testing duration, is required to confirm the
      potential accommodation trend.

PMID- 21178929
TI  - Effect of active stretch on hip flexion range of motion in female professional
      futsal players.
AB  - AIM: The purpose of this study was to determine the hamstring flexibility
      progression through hip flexion passive range of motion before (baseline hip
      flexion PROM, lasting 6 weeks), during (effect of stretching program, lasting 8
      weeks) and after (flexibility retention, lasting 4 weeks) an 8-week active
      stretching program in female professional futsal players. METHODS: Eighteen young
      adult professional female futsal players completed this study. An uninterrupted,
      longitudinal repeated-measures design was employed with participants randomly
      assigned into two groups: control and stretching group. The stretching group
      performed an 8-week active stretching program. The unilateral passive straight
      leg raise test was used to assess hip flexion PROM (hamstring extensibility) at
      2, 4, and 6 weeks before the stretching program, at 2, 4, 6, and 8 weeks during
      the stretching program and at 2 and 4 weeks after the stretching program.
      RESULTS: The analysis of the initial phase revealed that baseline hip flexion
      PROM had an irregular tendency with positive and negative peak hamstring ROM. An
      8-week active stretching program improved hip flexion ROM 26.0+/-8.8% (P<0.05).
      Four weeks after the stretching program ended, hip flexion PROM retention showed
      a significant decrease (P<0.05). CONCLUSION: The effect of acute stretching prior
      to intensive physical activities should be considered by strength and
      conditioning specialists before using this active stretching program as part of a
      pre-exercise warm up routine.

PMID- 21178930
TI  - The cardiovascular and metabolic responses to Wii Fit video game playing in
      middle-aged and older adults.
AB  - AIM: The purpose of this study was (a) to assess the cardiovascular and metabolic
      responses to Wii Fit video games and (b) to determine if Wii Fit video games meet
      the American College of Sports Medicine guidelines for improving and maintaining
      cardiorespiratory fitness. METHODS: Twenty men and women (mean+/-SD age, height,
      and weight: = 58.1+/-8.8 years, 172.1+/-10.5 cm, 87.1+/-22.8 kg, respectively)
      completed a 20-min Wii Fit testing session consisting of six separate aerobic and
      balance games. Cardiovascular and metabolic data were collected via a portable
      calorimetric measurement system. RESULTS: Mean relative exercise intensity was
      43.4+/-16.7% of heart rate reserve. Absolute exercise intensity in metabolic
      equivalents (METS) was 3.5+/-0.96. Total net energy expenditure for the Wii Fit
      video game playing session was 116.2+/-40.9 kcal/session. CONCLUSION: Results
      indicate that playing Wii Fit video games is a feasible alternative to more
      traditional aerobic exercise modalities for middle-aged and older adults that
      fulfills the American College of Sports Medicine guidelines for improving and
      maintaining cardiorespiratory fitness.

PMID- 21178931
TI  - High aerobic fitness is associated with lower total and regional adiposity in 12
      year-old overweight boys.
AB  - AIM: The objective of the present study was to determine relationship between
      aerobic (cardiovascular) fitness and body composition in both non-overweight and
      overweight 12-year-old school boys. METHODS: A cross-sectional study was
      conducted in a random sample of 10 elementary schools. The study participants
      were a 170 healthy fifth-grade elementary school boys aged 11.9+/-0.4 years.
      Anthropometric data (height, body mass, waist circumference, abdominal skinfold
      thickness) were collected according to standard procedure. Total body fat and
      muscle mass percentage were assessed by bioimpedance analysis. Body Mass Index
      (BMI) age-specific cutoff points were used for overweight definition and boys
      were placed in two groups overweight and non-overweight. Aerobic fitness (VO2max)
      was assessed with the multistage shuttle-run fitness test. Boys were grouped into
      high (upper two quintiles) and low (lower two quintiles) aerobic fitness based on
      age distribution. RESULTS: Waist circumference, abdominal skinfold thickness and
      total body fat were lower while muscle mass percentage was higher in overweight
      boys with high aerobic fitness in comparison with boys at the same BMI category
      with low fitness level (P<0.05). Aerobic fitness was inversely correlated with
      body fat in the whole group of subjects (r=-0,57, P<0.05), with particularly high
      correlation between VO2max and muscle mass in overweight boys (r=0.68, P<0.05).
      CONCLUSION: Indicators of local and total adiposity were lower in boys with high
      aerobic fitness. It seems that high aerobic fitness has is positively associated
      with body composition in overweight boys.

PMID- 21178932
TI  - Changes in total body and limb composition and muscle strength after a 6-8 weeks
      sojourn at extreme altitude (5000-8000 m).
AB  - AIM: Weight loss at extreme altitudes affects quantitative changes in fat-free
      mass (FFM), muscle mass and fat mass. No studies to date have focused on regional
      body composition and physical performance using reference methods after stays at
      extreme altitudes. The aim of this study was to investigate the changes in total
      and regional body composition, and muscle strength induced by the extreme
      altitudes. METHODS: Eight men aged 38.8+/-5.8 who took part in two different
      Italian expeditions on Mt. Everest (group A) and on Gasherbrum II (group B).
      Before and after the expedition all participants underwent anthropometric
      measurements, total and regional body composition assessment by DEXA, and
      handgrip and knee extensor strength measurements by dynamometry. RESULTS: The
      variations in body composition mainly involved FFM, with a similar loss in group
      A (-2.4+/-1.9 kg; P<0.05) and group B (-2.4+/-1.2 kg; P<0.05). Most of the FFM
      loss involved the limbs (-2.1+/-1.4 kg; P<0.01), and especially the upper limbs (
      1.6+/-1.1 kg; P<0.01). The isotonic knee extensor strength declined in 6 of the 8
      study participants, with a mean drop of -4.4+/-6.1 kg. CONCLUSIONS: In
      conclusion, our study evidence that extreme altitudes induce weight loss due
      mainly to a loss of fat-free mass in the limb.

PMID- 21178933
TI  - Effects of caffeine on repeated sprint ability, reactive agility time, sleep and
      next day performance.
AB  - AIM: This study assessed the effects of caffeine on repeated sprint ability
      (RSA), reactive agility time (RAT), sleep and next day exercise performance.
      METHODS: Ten moderately trained male athletes (single-blind, randomized,
      crossover design) ingested either caffeine (6 mg.kg-1 bm) or placebo 1 h before
      exercise. Trials were performed on the same day one week apart. Performance
      measures included a RAT test (10 trialsY10.2 m, separated by 30 s), followed by 7
      min of active recovery and then a RSA test (five sets of 6Y20 m sprints with 25
      or 60 s of recovery). The RSA was then followed by 5 min of active recovery and
      another RAT. That night, participants wore a wrist sleep actigraph to bed. Next
      day, participants repeated the RAT and the first set of the RSA tests. RESULTS:
      Significant improvements were demonstrated after caffeine ingestion compared to
      placebo for the combined total time of each set (TT; combined sets 1, 3, 5;
      58.947+/-1.88 vs. 59.683+/-2.54 s, respectively; P=0.05), best sprint time (BT;
      next day performance; 3.176+/-0.10 vs. 3.230+/-0.12 s, respectively, P=0.01), and
      % decrement (combined sets 2, 4; 2.866+/-1.24 vs. 3.801+/-1.69 s, respectively;
      P=0.02). Moderate to strong effect sizes were found for % decrement for set 2
      (Cohen's d=-0.82; 1.312+/-0.65 vs. 2.110+/-1.20 s for caffeine and placebo
      conditions, respectively) and for sets 2 and 4 combined (Cohen's d=-0.63; 2.866+/
      1.24 vs. 3.801+/-1.69 for caffeine and placebo conditions, respectively). No
      significant differences were found for RAT or for sleep measures (P>0.05).
      CONCLUSION: Caffeine improved RSA, including next day performance, but had little
      effect on RAT or sleep parameters.

PMID- 21178934
TI  - Multivariate isokinetic strength asymmetries of the knee and ankle in
      professional soccer players.
AB  - AIM: Soccer players possess various degrees of functional footedness. Their lower
      limbs are subjected to consistent asymmetrical workloads and neuromuscular
      adaptations, and as a result develop asymmetrical patterns of musculoskeletal
      function. This study focused on the myodynamic profile of the knee and ankle
      joint in professional soccer players. Special emphasis was put on the
      multivariate quantification of three types of asymmetry: directional (left vs.
      right), fluctuating (dominant vs. non dominant) and absolute (left vs. right).
      METHODS: One-hundred professional soccer players (mean age 23.4 years, weight
      73.3, height 177.6) were tested isokinetically for concentric and eccentric
      isokinetic muscle strength (1) of the knee flexors and extensors, and (2) of the
      ankle dorsal and plantar flexors. Knee flexion-extension was tested at 60o, 180o
      and 300o/s for the concentric mode of contraction and at 60o and 180o/s for the
      eccentric. The ankle joint was tested only at 60o/s for both the concentric and
      eccentric action. RESULTS: MANOVA showed significances for all three types of
      strength asymmetry (joint and action combined): directional (Wilks' Lambda=0.66,
      F=2.957, P=0.001), fluctuating (Wilks' Lambda=0.61, F=2.957, P=0.007), and
      absolute asymmetry (Wilks' Lambda=0.47, F=116.26, P=0.000). Several significant
      asymmetries were also revealed at the univariate level of analysis (P<0.05).
      CONCLUSION: It seems that the lower limbs of professional soccer players are
      characterized by significant compound muscle strength asymmetries. These findings
      substantiate the idea of asymmetry in the myodynamic adaptations that take place
      at the knee and ankle joint of soccer players during the game. Individual
      modification of the training load, targeting in strength asymmetry correction,
      should be taken into consideration for injury prevention.

PMID- 21178935
TI  - Training patterns and negative health outcomes in triathlon: longitudinal
      observations across a full competitive season.
AB  - AIM: Despite heavy training requirements, triathlon is a sport that is rapidly
      increasing in popularity. Yet, there is limited research detailing the
      relationship between training, the incidence of injuries and illness,
      psychological stress, overtraining and athlete burnout amongst triathletes. Six
      hypotheses relating inter-individual differences to training factors were
      generated to evaluate change in self-reported measures of these negative health
      outcomes over a training year. METHODS: Thirty, well-trained, triathletes (males
      n=20: age=27.1+/-9.1 years and females n=10: age=27.4+/-6.6 years) from a local
      triathlon club participated in this study. The study commenced during pre-season
      training, and involved weekly monitoring of each athlete until the end of the
      competitive season 45 weeks later. Linear Mixed Modelling was used for the
      analysis. RESULTS: Signs and symptoms of injury and illness (SAS) were
      significantly associated with increases in training factors (P<=0.05); however,
      greatest impact on SAS was produced by psychological stressors (P<=0.001). Common
      symptoms of overtraining were significantly affected by increases in exposure to
      both training and psychological stressors (P<=0.05). Mood disturbance was not
      significantly affected by training factors (P>0.05) but rather increases in
      psychological stressors (P<=0.001). Finally, each of the three athlete burnout
      subscales were significantly affected by both psychological (P<=0.001) stressors
      as well as varying combinations of training factors (P<=0.05). CONCLUSIONS:
      Exposure to stressors (either training or psychological) had significant effects
      on all negative health outcomes assessed.

PMID- 21178936
TI  - Growth factors in the management of sport-induced tendinopathies: results after
      24 months from treatment. A pilot study.
AB  - AIM: The efficacy of PRP in the treatment of tendinopathies has been already
      studied both in in vitro and in clinical studies. This paper describes the local
      and the systemic effects of US-guided autologous PRP (Platelet Rich Plasma)
      injections in chronic tendinopathies in sportspersons. METHODS: Fifteen patients
      (13 male, 2 female) between 17 and 68 years old, affected by chronic
      tendinopathies at different sites were treated with an echographically guided
      injection of autologous PRP within the pathological area of the tendons. VISA
      score and MRI data were collected pre interventions and after 90 days and 24
      months from treatment. Changes in different inteleukins (ILs), tumour necrosis
      factor alpha (TNF alpha), interferon gamma, vascular endothelial growth factor
      (VEGF), endothelial growth factor (EGF), chemokine (C-C motif) ligand 2 (CCL2),
      were analysed at four time points in the peripheral blood of five patients.
      RESULTS: After 90 days the VISA score significantly improved from 36+/-12 (range
      21-64) to 74+/-17 (range 40-92). Reduction of irregularities was found in 80% of
      the tendons. After 24 months patients reported an average VISA score of 73+/-16
      (range 42-100). No changes in IL, TNF alpha and interferon gamma were observed.
      VEGF, EGF and CCL2 decreased progressively from 30m to 3 h after the treatment
      and returned to near the baselines after 24 h. CONCLUSION: PRP injection allow an
      improvement of the clinical symptomatology, which is well maintained at least for
      two years from treatment. The PRP-based local therapy could influence systems
      homeostasis and antidoping evaluations, but, in our opinion, it doesn't represent
      a doping substance in itself.

PMID- 21178937
TI  - The effect of aerobic exercise on glycosylated hemoglobin values in type 2
      diabetes patients.
AB  - AIM: The changes of glycosylated hemoglobin A1c values have been considered as an
      important marker of glucose control over time. On the other hand, benefit of
      exercise in the control of glycemia is well known. The purpose of the present
      study was to investigate the influence of aerobic exercise program on A1c values
      and glycemic control in type 2 diabetic patients. METHODS: In this randomized,
      controlled trial, 65 participants aged 40 to 65 years with type 2 diabetes were
      randomly divided into 2 groups (30 controls and 35 exercises). The exercise
      training group performed aerobic training for 16 weeks (3 days/week, 90 min, 50
      80%VO2max) and the control group did not perform any exercise. Finally, 60
      subjects completed the program, and their results were analyzed to assess the A1c
      changes. RESULTS: After a 16-week aerobic exercise program the mean A1c value
      significantly reduced in the exercise training group in comparison with the
      control group (-0.73+/-1.4% vs. +0.28+/-0.60%, P<0.001). No serious adverse event
      was observed in the training sessions. As secondary outcomes, changes of baseline
      parameters (i.e. fasting blood glucose, body mass index, and blood pressure) were
      statistically significant. The reduction of blood pressure in control group was
      also significant. CONCLUSION: In patients with type 2 diabetes, significant
      improvement in A1c value and better glycemic control could be achieved by a
      regular exercise program as an intervention.

PMID- 21178938
TI  - One year follow-up in a group of half-marathon runners with type-1 diabetes
      treated with insulin analogues.
AB  - AIM: The objective was to describe the strategies that type-1 diabetic runners
      treated with insulin analogues apply in a half-marathon race and the changes
      after a year of experience participating in long-distance athletic competitions.
      METHODS: Fourteen male amateur athletes with type-1 diabetes treated with insulin
      analogues, participating in two consecutive editions of the same half-marathon
      were assessed. Data about insulin dosage and carbohydrate intake from their
      regular daily training and from the two half-marathons were compared. Capillary
      glycemic values from throughout the competition and in the following 24 h period
      were monitored and the frequency of hypoglycemia and glucose fluctuations was
      compared, using MAGE method. RESULTS: During the half-marathon day, athletes
      reduced total insulin doses a 18.3% in 2006 and 14.2% in 2007, with a reduction
      of basal insulin (23.3% in 2006 vs 20.4% in 2007, P<0.05) and of short-insulin at
      breakfast prior to the competition (31.7% in 2006 vs 15.3% in 2007, P<0.001).
      Carbohydrate consumption during competition was higher in second edition (49.0+/
      16.4 g vs 59.1+/-11.2 g, P<0.05). Glycaemic excursions, assessed by MAGE, were
      higher in the first edition (108.1+/-47.3 mg/dL vs 62.2+/-45.6 mg/dL, P<0.05).
      CONCLUSION: Type-1 diabetes athletes, treated with insulin analogues,
      participating in half-marathon competitions exhibited less insulin reduction in
      comparison with traditional guidelines and they needed to take an important
      quantity of carbohydrate supplements to avoid hypoglycemia during and after the
      competition. We suggest reconsidering traditional recommendations of insulin
      therapy and carbohydrate supplementation (amount and timing) to athletes treated
      with current insulin analogues participating in long-distance competitions.

PMID- 21178939
TI  - Effects of a supervised exercise program on the physical fitness and
      immunological function of HIV-infected patients.
AB  - AIM: Exercise effects in subjects with HIV/AIDS are not entirely understood. The
      study aimed to investigate the effects of a supervised exercise program on the
      physical fitness and immunological function of HIV-infected subjects. METHODS:
      Twenty-seven highly active antiretroviral therapy treated HIV-infected patients
      (age: 45+/-2 years; CD4-T: 21.3+/-2.2%) were assigned to a control (CG, n=8) or
      experimental (EG, n=19) group. The EG participated in a 12-week exercise program,
      consisting of aerobic training, strength, and flexibility exercises (3 times/wk;
      aerobic-30min: PWC 150; strength-50min: 3 sets of 12 reps of 5 exercises at 60
      80% 12 RM; flexibility-10min: 2 sets of 30 s at maximal range of motion of 8
      exercises). RESULTS: Prior to training there was no significant difference in any
      variable between the EG and the CG. Flexibility (23%, P<0.05), 12 repetition
      maximum in the leg press and seated bilateral row exercises (54% and 65%
      respectively, P<0.05) increased, while the heart rate at a given cycle ergometer
      workload declined (19% for slope and 12% for intercept, P<0.05) in the EG, but
      not in the CG. No significant differences were found for the relative and
      absolute CD4 T-cell counts between groups prior to or after training, but there
      was a slight enhancement trend in the EG (16%, P=0.19). CONCLUSION: Overall
      training can improve the muscle and aerobic fitness of HIV-infected patients with
      no negative effect on their immunological function.

PMID- 21178940
TI  - The effect of high level tennis matches on urine steroid profiles in professional
      tennis players.
AB  - AIM: Modern day, tennis matches are characterized by shorter and more intense
      efforts with players enduring great physical and psychological stress. The aim of
      this study was to evaluate acute changes in the urinary steroid profile of elite
      tennis players following professional tournament matches. METHODS: Eight
      professional male tennis players participated in this study. Urine samples were
      collected before and after tennis matches corresponding to the quarter finals of
      the Spanish Tennis Masters. RESULTS: After the match, there was a significant
      fall (P<0.05) in testosterone, androsterone, etiocholanolone, and
      dehydroepiandrosterone (DHEA). Cortisone increased whereas tetrahydrocortisone
      (THE) decreased. The anabolic/catabolic hormone ratio also decreased, although
      only the fall in total suprarenal androgen (TSA)/total corticosteroid (TC) and
      DHEA/(THE+THF) ratios had a significant decrease (P<0.05). CONCLUSION: These
      results indicate that a professional tennis match modifies the urine steroid
      profiles of players, increasing corticosteroid and decreasing androgen excretion
      in urine, suggesting an important adrenal activation.

PMID- 21178941
TI  - Performance improvement is associated with higher postexercise responses in
      interleukin-6 and tumor necrosis factor concentrations.
AB  - AIM: The aim of this study was to investigate the postexercise concentrations in
      IL-6 and TNF-alpha during maximal 6000 meter time trial in conditions with
      improved performance capacity. METHODS: Nine highly trained male rowers (age
      19.67+/-1.0; height 190.67+/-4.24 cm; weight 91.07+/-6.24 kg) participated.
      Subjects were asked for body composition measurement and two 6000 meter all-out
      rowing ergometer trial separated by one year. RESULTS: The 6000 meter rowing
      ergometer performance was significantly improved during one year period from from
      Test 1 to Test 2 (from 330.3+/-21.9 W to 349.2+/-20.3 W, P<0.05). No significant
      changes were observed in the anthropometrical parameters. Postexercise cortisol
      and IL-6 were significantly increased during both testing sessions, while TNF
      alpha was only increased after Test 2 when compared to pretest values.
      Postexercise and post 30 values of TNF-alpha were significantly higher at Test 2
      compared to Test 1, while only Post 30 values of IL-6 were significantly higher
      at Test 2 compared to Test 1. There were no significant relationship between
      postexercise IL-6 and TNF-alpha concentrations and the 6000 meter rowing
      ergometer performance (r=-0.101 - -0.617; P>0.05) and no signigficant
      relationships between the measured body compositional and blood biochemical
      parameters. Postexercise changes in IL-6 concentration were significantly related
      to changes in performance (r=-0.667 and r=-0.865 for POST and POST 30,
      respectively; P<0.05). CONCLUSION: In conclusion improvements in performance
      resulted in higher postexercise concentrations of IL-6 and TNF-alpha in highly
      trained male rowers.

PMID- 21178942
TI  - IGF-1 abuse in sport: clinical and medico-legal aspects.
AB  - The frequent revisions of prohibited substances list established by WADA are
      aimed at keeping up with those drugs that, being increasingly used in medicine
      and in sports, play on one side a therapeutic role and, on the other, a doping
      role. Among the various hormone substances widely used in sports, the authors
      draw particular attention on IGF-1, a growth factor that is rapidly widespreading
      among athletes. Moreover, IGF-1 diffusion is not exclusively correlated with the
      doping phenomenon, being various the pathological conditions that may require the
      therapeutic use of this substance. As a consequence, during pathologies or
      medical treatments of various nature, the athletes should be informed of the IGF
      1 administration because, if they are not duly apprised, they risk undergoing
      unjust sanctions from the competent authority. In fact, the athlete is given the
      possibility of communicating, before using, he is taking a medication of the WADA
      list for therapeutic reasons by applying for a TUE (Therapeutic Use Exemption).
      If this application is accepted on certified clinical grounds, the athlete will
      be allowed to use that substance even during sports competitions. However, the
      IGF-1 detection in the athlete's body shows, at the present state-of-art, two
      different problems: the first one has a technical character and concerns the
      differential diagnosis between the quantity of the physiologically produced
      substance and the quantity of the exogenously administrated substance; the second
      problem has an economic character and regards to the high cost of the analysis
      and, consecutively, the necessity of finding a well-equipped laboratory centre.

PMID- 21178943
TI  - The cortisol awakening response and autonomic nervous system activity during
      nocturnal and early morning periods.
AB  - The current study focuses on autonomic nervous system activity during sleep as a
      physiological aspect of sleep quality, and investigated the associations between
      the cortisol awakening response (CAR) and autonomic activity during sleep and
      after awakening. Ambulatory electrocardiograms were obtained from 20
      participants, who also provided saliva samples (at the time of awakening, and 30,
      45, and 60 min after awakening) and rated the subjective quality of their sleep
      at home. Autonomic activity was assessed with the Lorenz plot indices, cardiac
      sympathetic index (CSI) and cardiac vagal index. Total salivary cortisol
      secretion after awakening was calculated as area under the curve with respect to
      ground (AUC(G)) and increase (AUC(I)). After controlling for confounding factors,
      including sleep duration and awakening time, cortisol AUC(G) and AUC(I) were both
      found to be negatively correlated with CSI during the 30 min before and after
      awakening: before (r = -0.526 and -0.601 respectively) and after (r = -0.540 and 
      0.493 respectively). Self-reported sleep quality was not associated with the CAR.
      These results suggest that the CAR is negatively affected by basal sympathetic
      activity immediately before and after awakening, but not affected by subjective
      sleep quality. Physiological arousals around the time of awakening might inhibit
      the CAR.

PMID- 21178944
TI  - Stress hormones predict hyperbolic time-discount rates six months later in
      adults.
AB  - OBJECTIVES: Stress hormones have been associated with temporal discounting.
      Although time-discount rate is shown to be stable over a long term, no study to
      date examines whether individual differences in stress hormones could predict
      individuals' time-discount rates in the relatively distant future (e.g., six
      month later), which is of interest in neuroeconomics of stress-addiction
      association. METHODS: We assessed 87 participants' salivary stress hormone
      (cortisol, cortisone, and alpha-amylase) levels and hyperbolic discounting of
      delayed rewards consisting of three magnitudes, at the time-interval of six
      months. For salivary steroid assays, we employed a liquid chromatography/ mass
      spectroscopy (LC/MS) method. The correlations between the stress hormone levels
      and time-discount rates were examined. RESULTS: We observed that salivary alpha
      amylase (sAA) levels were negatively associated with time-discount rates in never
      smokers. Notably, salivary levels of stress steroids (i.e., cortisol and
      cortisone) negatively and positively related to time-discount rates in men and
      women, respectively, in never-smokers. Ever-smokers' discount rates were not
      predicted from these stress hormone levels. CONCLUSIONS: Individual differences
      in stress hormone levels predict impulsivity in temporal discounting in the
      future. There are sex differences in the effect of stress steroids on temporal
      discounting; while there was no sex defference in the relationship between sAA
      and temporal discounting.

PMID- 21178945
TI  - Results and effects in the diagnosis and treatment of diseases received in
      medical practice from "Complex medical expert" (CME).

PMID- 21178946
TI  - An open-label trial of L-5-hydroxytryptophan in subjects with romantic stress.
AB  - This open-label trial assessed the clinical efficacy of L-5-hydroxytryptophan (5
      HTP), a natural serotonin precursor, in nondepressed young subjects with high
      levels of romantic stress. Since both neurotrophins and serotonin have been
      linked to human romantic attachment, we sought to investigate the changes in
      serum brain-derived neurotrophic factor (BDNF) levels and platelet serotonin
      content in relation to the changes in romantic stress throughout the study. A
      total of 15 healthy subjects (11 females and 4 males, mean age: 23.3 +/- 2.1
      years) who experienced a recent romantic break-up or reported recent romantic
      problems took part in the study. The participants were treated openly for 6 weeks
      with L-5-hydroxytryptophan (60 mg Griffonia simplicifolia extract containing 12.8
      mg 5-HTP b.i.d., Amorex, Coropharm, Villach, Austria). The subjects were
      evaluated at baseline, at 3 weeks and at the end of the 6-week trial using an
      adapted version of the Seiffge-Krenke's Problem Questionnaire. BDNF and platelet
      serotonin content were determined at baseline, at 3 weeks, and after the
      completion of the 6-week trial. We observed significant improvements in romantic
      stress scores from weeks 0 through 3 (p=0.007) but no further significant
      improvement was evident from weeks 3 through 6 (p=0.19). At 6 weeks, subjects had
      a significant increase from baseline in both BDNF and platelet serotonin values.
      Our data suggest that direct modulation of the serotonergic system may have use
      for the treatment of psychological suffering associated with unreciprocated
      romantic love.

PMID- 21178947
TI  - Update on cholera --- Haiti, Dominican Republic, and Florida, 2010.
AB  - On October 21, 2010, a cholera outbreak was confirmed by the Haitian National
      Public Health Laboratory. By November 19, the outbreak had reached every
      department of the country, and by December 17, a total of 121,518 cases of
      cholera, resulting in 63,711 hospitalizations and 2,591 deaths, had been
      reported. By November 16, additional cases of cholera had been confirmed in the
      neighboring Dominican Republic and in Florida. Several confirmed cases in the
      Dominican Republic and all confirmed U.S. cases were among travelers from Haiti.
      This report describes cases of cholera identified in the Dominican Republic and
      United States and provides recommendations to physicians regarding management of
      travel-related cases. Travelers who develop watery diarrhea within 5 days after
      returning from cholera-affected areas should seek health care and report their
      travel histories. Clinicians should enquire about recent travel when evaluating
      patients with diarrhea. When cholera is suspected, rehydration should be
      initiated immediately, a stool specimen should be collected for culture of Vibrio
      cholerae, and public health authorities should be notified.

PMID- 21178948
TI  - Transmission of multidrug-resistant Escherichia coli through kidney
      transplantation --- California and Texas, 2009.
AB  - On July 6, 2009, the Organ Procurement and Transplantation Network received
      notification of possible disease transmission. A transplant center in California
      (TCA) reported a kidney transplant recipient with Escherichia coli urinary tract
      infection and sepsis suspected to have been contracted from the donated kidney.
      Upon further investigation, a transplant center in Texas (TCB) reported that the
      recipient of the other kidney from the same donor developed a perinephric abscess
      caused by E. coli. The kidney grafts failed in both recipients; however, both
      recipients survived. E. coli isolates from both recipients demonstrated similar
      antimicrobial susceptibility profiles. Molecular typing studies conducted at CDC
      showed that the E. coli isolates from both kidney recipients were identical to an
      isolate from the donor's urine. On October 30, 2009, the Texas Department of
      State Health Services requested assistance from CDC to investigate this
      transplant-associated E. coli transmission and make recommendations to prevent
      future transmissions. The investigation identified gaps in communicating
      important donor information that might have adversely affected transplant
      outcomes. Each organ procurement organization (OPO) should establish protocols
      that clearly assign responsibilities for receiving, reviewing, and conveying any
      relevant donor information that becomes available subsequent to organ
      procurement.

PMID- 21178949
TI  - Salmonella montevideo infections associated with salami products made with
      contaminated imported black and red pepper --- United States, July 2009-April
      2010.
AB  - In August and September 2009, PulseNet, the national molecular subtyping network
      for foodborne disease surveillance, detected a multistate cluster of Salmonella
      Montevideo infections with an indistinguishable pulse-field gel electrophoresis
      (PFGE) pattern (XbaI PFGE pattern JIXX01.0011). Cases were geographically
      dispersed, and the age and sex distributions were typical for reported Salmonella
      cases. Montevideo is the seventh most common Salmonella serotype in the United
      States; of 1,225 PFGE patterns in the PulseNet Montevideo database, the outbreak
      strain pattern is the most common. PulseNet monitored this pattern and detected
      an increase in the number of isolates in November 2009, leading CDC to begin
      coordinating a multistate investigation. This report summarizes the results of
      that investigation, which identified 272 cases from 44 states and the District of
      Columbia, with illness onset from July 1, 2009, to April 14, 2010. In a
      multistate case-control study, consumption of salami was associated with illness.
      Purchase information from membership card records helped determine specific
      brands of Italian-style meat products associated with cases. The outbreak strain
      was identified in salami products, one company A facility environmental sample,
      and sealed containers of black and red pepper used to produce company A salami
      products. This outbreak highlights the importance of preventing post-processing
      contamination of ready-to-eat products from raw ingredients such as spices.

PMID- 21178950
TI  - Update: influenza activity --- United States, October 3-December 11, 2010.
AB  - During October 3-December 11, 2010, influenza activity remained low in most
      regions of the United States. Influenza viruses characterized thus far in the
      influenza season are well matched to the strains included in the 2010-11
      influenza vaccine. This report summarizes U.S. influenza activity during this
      period.

PMID- 21178951
TI  - Enzyme-linked immunospot assay (ELISPOT): Quantification of Th-1 cellular immune
      responses against microbial antigens.
AB  - Adaptive immunity is an important component to clearance of intracellular
      pathogens. The ability to detect and quantify these responses in humans is an
      important diagnostic tool. The enzyme-linked immunospot assay (ELISPOT) is
      gaining popularity for its ability to identify cellular immune responses against
      microbial antigens, including immunosuppressed populations such as those with HIV
      infection, transplantation, and steroid use. This assay has the capacity to
      quantify the immune responses against specific microbial antigens, as well as
      distinguish if these responses are Th1 or Th2 in character. ELISPOT is not
      limited to the site of inflammation. It is versatile in its ability to assess for
      immune responses within peripheral blood, as well as sites of active involvement
      such as bronchoalveolar lavage, cerebral spinal fluid, and ascites. Detection of
      immune responses against a single or multiple antigens is possible, as well as
      specific epitopes within microbial proteins. This assay facilitates detection of
      immune responses over time, as well as distinctions in antigens recognized by
      host T cells. Dual color ELISPOT assays are available for detection of
      simultaneous expression of two cytokines. Recent applications for this technique
      include diagnosis of extrapulmonary tuberculosis, as well as investigation of the
      contribution of infectious antigens to autoimmune diseases.

PMID- 21178952
TI  - Alphavirus transducing system: tools for visualizing infection in mosquito
      vectors.
AB  - Alphavirus transducing systems (ATSs) are important tools for expressing genes of
      interest (GOI) during infection. ATSs are derived from cDNA clones of mosquito
      borne RNA viruses (genus Alphavirus; family Togaviridae). The Alphavirus genus
      contains about 30 different mosquito-borne virus species. Alphaviruses are
      enveloped viruses and contain single-stranded RNA genomes (~11.7 Kb).
      Alphaviruses transcribe a subgenomic mRNA that encodes the structural proteins of
      the virus required for encapsidation of the genome and maturation of the virus.
      Alphaviruses are usually highly lytic in vertebrate cells, but persistently
      infect susceptible mosquito cells with minimal cytopathology. These attributes
      make them excellent tools for gene expression in mosquito vectors. The most
      common ATSs in use are derived from Sindbis virus (SINV). The broad species
      tropism of SINV allows for infection of insect, avian, and mammalian cells8.
      However, ATSs have been derived from other alphaviruses as well. Foreign gene
      expression is made possible by the insertion of an additional viral subgenomic
      RNA initiation site or promoter. ATSs in which an exogenous gene sequence is
      positioned 5' to the viral structural genes is used for stable protein expression
      in insects. ATSs, in which a gene sequence is positioned 3' to the structural
      genes, is used to trigger RNAi and silence expression of that gene in the insect.
      ATSs have proven to be valuable tools for understanding vector-pathogen
      interactions, molecular details of viral replication and maintenance infectious
      cycles. In particular, the expression of fluorescent and bioluminescent reporters
      has been instrumental tracking the viral infection in the vector and virus
      transmission. Additionally, the vector immune response has been described using
      two strains of SINV engineered to express GFP(2,9). Here, we present a method for
      the production of SINV containing a fluorescent reporter (GFP) from the cDNA
      infectious clone. Infectious, full-length RNA is transcribed from the linearized
      cDNA clone. Infectious RNA is introduced into permissive target cells by
      electroporation. Transfected cells generate infectious virus particles expressing
      the GOI. Harvested virus is used to infect mosquitoes, as described here, or
      other host species (not shown herein). Vector competence is assessed by detecting
      fluorescence outside the midgut or by monitoring virus transmission. Use of a
      fluorescent reporter as the GOI allows for convenient estimation of virus spread
      throughout a cell culture, for determination of rate of infection, dissemination
      in exposed mosquitoes, virus transmission from the mosquito and provides a rapid
      gauge of vector competence.

PMID- 21178953
TI  - Generation of RNA/DNA hybrids in genomic DNA by transformation using RNA
      containing oligonucleotides.
AB  - Synthetic short nucleic acid polymers, oligonucleotides (oligos), are the most
      functional and widespread tools of molecular biology. Oligos can be produced to
      contain any desired DNA or RNA sequence and can be prepared to include a wide
      variety of base and sugar modifications. Moreover, oligos can be designed to
      mimic specific nucleic acid alterations and thus, can serve as important tools to
      investigate effects of DNA damage and mechanisms of repair. We found that Thermo
      Scientific Dharmacon RNA-containing oligos with a length between 50 and 80
      nucleotides can be particularly suitable to study, in vivo, functions and
      consequences of chromosomal RNA/DNA hybrids and of ribonucleotides embedded into
      DNA. RNA/DNA hybrids can readily form during DNA replication, repair and
      transcription, however, very little is known about the stability of RNA/DNA
      hybrids in cells and to which extent these hybrids can affect the genetic
      integrity of cells. RNA-containing oligos, therefore, represent a perfect vector
      to introduce ribonucleotides into chromosomal DNA and generate RNA/DNA hybrids of
      chosen length and base composition. Here we present the protocol for the
      incorporation of ribonucleotides into the genome of the eukaryotic model system
      yeast /Saccharomyces cerevisiae/. Yet, our lab has utilized Thermo Scientific
      Dharmacon RNA-containing oligos to generate RNA/DNA hybrids at the chromosomal
      level in different cell systems, from bacteria to human cells.

PMID- 21178954
TI  - Experimental metastasis and CTL adoptive transfer immunotherapy mouse model.
AB  - Experimental metastasis mouse model is a simple and yet physiologically relevant
      metastasis model. The tumor cells are injected intravenously (i.v) into mouse
      tail veins and colonize in the lungs, thereby, resembling the last steps of tumor
      cell spontaneous metastasis: survival in the circulation, extravasation and
      colonization in the distal organs. From a therapeutic point of view, the
      experimental metastasis model is the simplest and ideal model since the target of
      therapies is often the end point of metastasis: established metastatic tumor in
      the distal organ. In this model, tumor cells are injected i.v into mouse tail
      veins and allowed to colonize and grow in the lungs. Tumor-specific CTLs are then
      injected i.v into the metastases-bearing mouse. The number and size of the lung
      metastases can be controlled by the number of tumor cells to be injected and the
      time of tumor growth. Therefore, various stages of metastasis, from minimal
      metastasis to extensive metastasis, can be modeled. Lung metastases are analyzed
      by inflation with ink, thus allowing easier visual observation and
      quantification.

PMID- 21178955
TI  - Production of chick embryo extract for the cultivation of murine neural crest
      stem cells.
AB  - The neural crest arises from the neuro-ectoderm during embryogenesis and persists
      only temporarily. Early experiments already proofed pluripotent progenitor cells
      to be an integral part of the neural crest(1). Phenotypically, neural crest stem
      cells (NCSC) are defined by simultaneously expressing p75 (low-affine nerve
      growth factor receptor, LNGFR) and SOX10 during their migration from the neural
      crest(2,3,4,5). These progenitor cells can differentiate into smooth muscle
      cells, chromaffin cells, neurons and glial cells, as well as melanocytes,
      cartilage and bone(6,7,8,9). To cultivate NCSC in vitro, a special neural crest
      stem cell medium (NCSCM) is required(10). The most complex part of the NCSCM is
      the preparation of chick embryo extract (CEE) representing an essential source of
      growth factors for the NCSC as well as for other types of neural explants. Other
      NCSCM ingredients beside CEE are commercially available. Producing CCE using
      laboratory standard equipment it is of high importance to know about the
      challenging details as the isolation, maceration, centrifugation, and filtration
      processes. In this protocol we describe accurate techniques to produce a
      maximized amount of pure and high quality CEE.

PMID- 21178956
TI  - An orthotopic model of serous ovarian cancer in immunocompetent mice for in vivo
      tumor imaging and monitoring of tumor immune responses.
AB  - BACKGROUND: Ovarian cancer is generally diagnosed at an advanced stage where the
      case/fatality ratio is high and thus remains the most lethal of all gynecologic
      malignancies among US women. Serous tumors are the most widespread forms of
      ovarian cancer and the Tg-MISIIR-TAg transgenic represents the only mouse model
      that spontaneously develops this type of tumors. Tg-MISIIR-TAg mice express SV40
      transforming region under control of the Mullerian Inhibitory Substance type II
      Receptor (MISIIR) gene promoter. Additional transgenic lines have been identified
      that express the SV40 TAg transgene, but do not develop ovarian tumors. Non-tumor
      prone mice exhibit typical lifespan for C57Bl/6 mice and are fertile. These mice
      can be used as syngeneic allograft recipients for tumor cells isolated from Tg
      MISIIR-TAg-DR26 mice. OBJECTIVE: Although tumor imaging is possible, early
      detection of deep tumors is challenging in small living animals. To enable
      preclinical studies in an immunologically intact animal model for serous ovarian
      cancer, we describe a syngeneic mouse model for this type of ovarian cancer that
      permits in vivo imaging, studies of the tumor microenvironment and tumor immune
      responses. METHODS: We first derived a TAg+ mouse cancer cell line (MOV1) from a
      spontaneous ovarian tumor harvested in a 26 week-old DR26 Tg-MISIIR-TAg female.
      Then, we stably transduced MOV1 cells with TurboFP635 Lentivirus mammalian vector
      that encodes Katushka, a far-red mutant of the red fluorescent protein from sea
      anemone Entacmaea quadricolor with excitation/emission maxima at 588/635 nm. We
      orthotopically implanted MOV1(Kat) in the ovary of non-tumor prone Tg-MISIIR-TAg
      female mice. Tumor progression was followed by in vivo optical imaging and tumor
      microenvironment was analyzed by immunohistochemistry. RESULTS: Orthotopically
      implanted MOV1(Kat) cells developed serous ovarian tumors. MOV1(Kat) tumors could
      be visualized by in vivo imaging up to three weeks after implantation (fig. 1)
      and were infiltrated with leukocytes, as observed in human ovarian cancers (fig.
      2). CONCLUSIONS: We describe an orthotopic model of ovarian cancer suitable for
      in vivo imaging of early tumors due to the high pH-stability and photostability
      of Katushka in deep tissues. We propose the use of this novel syngeneic model of
      serous ovarian cancer for in vivo imaging studies and monitoring of tumor immune
      responses and immunotherapies.

PMID- 21178957
TI  - Surgical management of meatal stenosis with meatoplasty.
AB  - Meatal stenosis is a common urologic complication after circumcision. Children
      present to their primary care physicians with complaints of deviated urinary
      stream, difficult-to-aim, painful urination, and urinary frequency. Clinical exam
      reveals a pinpoint meatus and if the child is asked to urinate, he will usually
      have an upward, thin, occasionally forceful urinary stream with incomplete
      bladder emptying. The mainstay of management is meatoplasty (reconstruction of
      the distal urethra /meatus). This educational video will demonstrate how this is
      performed.

PMID- 21178958
TI  - Targeting of deep brain structures with microinjections for delivery of drugs,
      viral vectors, or cell transplants.
AB  - Microinjections into the brain parenchyma are important procedures to deliver
      drugs, viral vectors or cell transplants. The brain lesion that an injecting
      needle produces during its trajectory is a major concern especially in the mouse
      brain for not only the brain is small but also sometimes multiple injections are
      needed. We show here a method to produce glass capillary needles with a 50-MUm
      lumen which significantly reduces the brain damage and allows a precise targeting
      into the rodent brain. This method allows a delivery of small volumes (from 20 to
      100 nl), reduces bleeding risks, and minimizes passive diffusion of drugs into
      the brain parenchyma. By using different size of capillary glass tubes, or
      changing the needle lumen, several types of substances and cells can be injected.
      Microinjections with a glass capillary tube represent a significant improvement
      in injection techniques and deep brain targeting with minimal collateral damage
      in small rodents.

PMID- 21178959
TI  - IP-FCM: immunoprecipitation detected by flow cytometry.
AB  - Immunoprecipitation detected by flow cytometry (IP-FCM) is an efficient method
      for detecting and quantifying protein-protein interactions. The basic principle
      extends that of sandwich ELISA, wherein the captured primary analyte can be
      detected together with other molecules physically associated within multiprotein
      complexes. The procedure involves covalent coupling of polystyrene latex
      microbeads with immunoprecipitating monoclonal antibodies (mAb) specific for a
      protein of interest, incubating these beads with cell lysates, probing captured
      protein complexes with fluorochrome-conjugated probes, and analyzing bead
      associated fluorescence by flow cytometry. IP-FCM is extremely sensitive, allows
      analysis of proteins in their native (non-denatured) state, and is amenable to
      either semi-quantitative or quantitative analysis. As additional advantages, IP
      FCM requires no genetic engineering or specialized equipment, other than a flow
      cytometer, and it can be readily adapted for high-throughput applications.

PMID- 21178960
TI  - Expression, detergent solubilization, and purification of a membrane transporter,
      the MexB multidrug resistance protein.
AB  - Multidrug resistance (MDR), the ability of a cancer cell or pathogen to be
      resistant to a wide range of structurally and functionally unrelated anti-cancer
      drugs or antibiotics, is a current serious problem in public health. This
      multidrug resistance is largely due to energy-dependent drug efflux pumps. The
      pumps expel anti-cancer drugs or antibiotics into the external medium, lowering
      their intracellular concentration below a toxic threshold. We are studying
      multidrug resistance in Pseudomonas aeruginosa, an opportunistic bacterial
      pathogen that causes infections in patients with many types of injuries or
      illness, for example, burns or cystic fibrosis, and also in immuno-compromised
      cancer, dialysis, and transplantation patients. The major MDR efflux pumps in P.
      aeruginosa are tripartite complexes comprised of an inner membrane proton-drug
      antiporter (RND), an outer membrane channel (OMF), and a periplasmic linker
      protein (MFP). The RND and OMF proteins are transmembrane proteins. Transmembrane
      proteins make up more than 30% of all proteins and are 65% of current drug
      targets. The hydrophobic transmembrane domains make the proteins insoluble in
      aqueous buffer. Before a transmembrane protein can be purified, it is necessary
      to find buffer conditions containing a mild detergent that enable the protein to
      be solubilized as a protein detergent complex (PDC). In this example, we use an
      RND protein, the P. aeruginosa MexB transmembrane transporter, to demonstrate how
      to express a recombinant form of a transmembrane protein, solubilize it using
      detergents, and then purify the protein detergent complexes. This general method
      can be applied to the expression, purification, and solubilization of many other
      recombinantly expressed membrane proteins. The protein detergent complexes can
      later be used for biochemical or biophysical characterization including X-ray
      crystal structure determination or crosslinking studies.

PMID- 21178961
TI  - Profiling of pre-micro RNAs and microRNAs using quantitative real-time PCR (qPCR)
      arrays.
AB  - Quantitative real-time PCR (QPCR) has emerged as an accurate and valuable tool in
      profiling gene expression levels. One of its many advantages is a lower detection
      limit compared to other methods of gene expression profiling while using smaller
      amounts of input for each assay. Automated qPCR setup has improved this field by
      allowing for greater reproducibility. Its convenient and rapid setup allows for
      high-throughput experiments, enabling the profiling of many different genes
      simultaneously in each experiment. This method along with internal plate controls
      also reduces experimental variables common to other techniques. We recently
      developed a qPCR assay for profiling of pre-microRNAs (pre-miRNAs) using a set of
      186 primer pairs. MicroRNAs have emerged as a novel class of small, non-coding
      RNAs with the ability to regulate many mRNA targets at the post-transcriptional
      level. These small RNAs are first transcribed by RNA polymerase II as a primary
      miRNA (pri-miRNA) transcript, which is then cleaved into the precursor miRNA (pre
      miRNA). Pre-miRNAs are exported to the cytoplasm where Dicer cleaves the hairpin
      loop to yield mature miRNAs. Increases in miRNA levels can be observed at both
      the precursor and mature miRNA levels and profiling of both of these forms can be
      useful. There are several commercially available assays for mature miRNAs;
      however, their high cost may deter researchers from this profiling technique.
      Here, we discuss a cost-effective, reliable, SYBR-based qPCR method of profiling
      pre-miRNAs. Changes in pre-miRNA levels often reflect mature miRNA changes and
      can be a useful indicator of mature miRNA expression. However, simultaneous
      profiling of both pre-miRNAs and mature miRNAs may be optimal as they can
      contribute nonredundant information and provide insight into microRNA processing.
      Furthermore, the technique described here can be expanded to encompass the
      profiling of other library sets for specific pathways or pathogens.

PMID- 21178962
TI  - Analysis of mRNA nuclear export kinetics in mammalian cells by microinjection.
AB  - In eukaryotes, messenger RNA (mRNA) is transcribed in the nucleus and must be
      exported into the cytoplasm to access the translation machinery. Although the
      nuclear export of mRNA has been studied extensively in Xenopus oocytes and
      genetically tractable organisms such as yeast and the Drosophila derived S2 cell
      line, few studies had been conducted in mammalian cells. Furthermore the kinetics
      of mRNA export in mammalian somatic cells could only be inferred indirectly. In
      order to measure the nuclear export kinetics of mRNA in mammalian tissue culture
      cells, we have developed an assay that employs the power of microinjection
      coupled with fluorescent in situ hybridization (FISH). These assays have been
      used to demonstrate that in mammalian cells, the majority of mRNAs are exported
      in a splicing dependent manner, or in manner that requires specific RNA sequences
      such as the signal sequence coding region (SSCR). In this assay, cells are
      microinjected with either in vitro synthesized mRNA or plasmid DNA containing the
      gene of interest. The microinjected cells are incubated for various time points
      then fixed and the sub-cellular localization of RNA is assessed using FISH. In
      contrast to transfection, where transcription occurs several hours after the
      addition of nucleic acids, microinjection of DNA or mRNA allows for rapid
      expression and allows for the generation of precise kinetic data.

PMID- 21178963
TI  - Orthotopic aortic transplantation: a rat model to study the development of
      chronic vasculopathy.
AB  - Research models of chronic rejection are essential to investigate pathobiological
      and pathophysiological processes during the development of transplant
      vasculopathy (TVP). The commonly used animal model for cardiovascular chronic
      rejection studies is the heterotopic heart transplant model performed in
      laboratory rodents. This model is used widely in experiments since Ono and
      Lindsey published their technique. To analyze the findings in the blood vessels,
      the heart has to be sectioned and all vessels have to be measured. Another method
      to investigate chronic rejection in cardiovascular questionings is the aortic
      transplant model. In the orthotopic aortic transplant model, the aorta can easily
      be histologically evaluated. The PVG-to-ACI model is especially useful for CAV
      studies, since acute vascular rejection is not a major confounding factor and
      Cyclosporin A (CsA) treatment does not prevent the development of CAV, similar to
      what we find in the clinical setting. A7-day period of CsA is required in this
      model to prevent acute rejection and to achieve long-term survival with the
      development of TVP. This model can also be used to investigate acute cellular
      rejection and media necrosis in xenogeneic models.

PMID- 21178964
TI  - Non-invasive imaging of leukocyte homing and migration in vivo.
AB  - Two-photon (2P) microscopy is a high resolution imaging technique that has been
      broadly adapted by biologists. The value of 2P microscopy is that it provides
      rich spatiotemporal information regarding cell behaviors within intact tissues
      and in live mice. Leukocyte recruitment plays a significant role in host defense
      against infection and when unchecked, can contribute to inflammatory and
      autoimmune diseases. Studying leukocyte recruitment in vivo is technically
      challenging since cells are moving rapidly within vessels located deep within
      light scattering tissues. To date, most intravital imaging studies require
      surgical preparation to expose the blood vessels and tissues. To avoid the tissue
      damage and inflammation induced by surgery itself, here, we describe a non
      invasive single-cell imaging approach that can be used to study leukocyte
      trafficking in the mouse footpad and phalanges. We discuss the technical aspects
      of our 2P imaging preparation and walk the reader through a typical experiment
      from initial set up to execution and data collection.

PMID- 21178965
TI  - Immunofluorescent detection of two thymidine analogues (CldU and IdU) in primary
      tissue.
AB  - Accurate measurement of cell division is a fundamental challenge in experimental
      biology that becomes increasingly complex when slowly dividing cells are
      analyzed. Established methods to detect cell division include direct
      visualization by continuous microscopy in cell culture, dilution of vital dyes
      such as carboxyfluorescein di-aetate succinimidyl ester (CFSE), immuno-detection
      of mitogenic antigens such as ki67 or PCNA, and thymidine analogues. Thymidine
      analogues can be detected by a variety of methods including radio-detection for
      tritiated thymidine, immuno-detection for bromo-deoxyuridine (BrdU), chloro
      deoxyuridine (CldU) and iodo-deoxyuridine (IdU), and chemical detection for
      ethinyl-deoxyuridine (EdU). We have derived a strategy to detect sequential
      incorporation of different thymidine analogues (CldU and IdU) into tissues of
      adult mice. Our method allows investigators to accurately quantify two successive
      rounds of cell division. By optimizing immunostaining protocols our approach can
      detect very low dose thymidine analogues administered via the drinking water,
      safe to administer to mice for prolonged periods of time. Consequently, our
      technique can be used to detect cell turnover in very long-lived tissues. Optimal
      immunofluoresent staining results can be achieved in multiple tissue types,
      including pancreas, skin, gut, liver, adrenal, testis, ovary, thyroid, lymph
      node, and brain. We have also applied this technique to identify oncogenic
      transformation within tissues. We have further applied this technique to
      determine if transit-amplifying cells contribute to growth or renewal of tissues.
      In this sense, sequential administration of thymidine analogues represents a
      novel approach for studying the origins and survival of cells involved in tissue
      homeostasis.

PMID- 21178966
TI  - Analysis of pluripotent stem cells by using cryosections of embryoid bodies.
AB  - Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass
      of blastocyst-stage early mammalian embryos. A crucial stage in the
      differentiation of ES cells is the formation of embryoid bodies (EBs) aggregates.
      EB formation is based on spontaneous aggregation when ES cells are cultured in
      non adherent plates. Three-dimensional EB recapitulates many aspects of early
      mammalian embryogenesis and differentiate into the three germ layers: ectoderm,
      mesoderm and endoderm. Immunofluorescence and in situ hybridization are widely
      used techniques for the detection of target proteins and mRNA present in cells of
      a tissue section. Here we present a simple technique to generate high quality
      cryosections of embryoid bodies. This approach relies on the spatial orientation
      of EB embedding in OCT followed by the cryosection technique. The resulting
      sections can be subjected to a wide variety of analytical procedures in order to
      characterize populations of cells containing certain proteins, RNA or DNA. In
      this sense, the preparation of EB cryosections (10 MUm) are essential tools for
      histology staining analysis (e.g. Hematoxilin and Eosin, DAPI),
      immunofluorescence (e.g. Oct4, nestin) or in situ hybridization. This technique
      can also help to understand aspects of embryogenesis with regards to the
      maintenance of the tri-dimensional spherical structure of EBs.

PMID- 21178967
TI  - Dual-mode imaging of cutaneous tissue oxygenation and vascular function.
AB  - Accurate assessment of cutaneous tissue oxygenation and vascular function is
      important for appropriate detection, staging, and treatment of many health
      disorders such as chronic wounds. We report the development of a dual-mode
      imaging system for non-invasive and non-contact imaging of cutaneous tissue
      oxygenation and vascular function. The imaging system integrated an infrared
      camera, a CCD camera, a liquid crystal tunable filter and a high intensity fiber
      light source. A Labview interface was programmed for equipment control,
      synchronization, image acquisition, processing, and visualization. Multispectral
      images captured by the CCD camera were used to reconstruct the tissue oxygenation
      map. Dynamic thermographic images captured by the infrared camera were used to
      reconstruct the vascular function map. Cutaneous tissue oxygenation and vascular
      function images were co-registered through fiduciary markers. The performance
      characteristics of the dual-mode image system were tested in humans.

PMID- 21178968
TI  - Methods development for blood borne macrophage carriage of nanoformulated
      antiretroviral drugs.
AB  - Nanoformulated drugs can improve pharmacodynamics and bioavailability while
      serving also to reduce drug toxicities for antiretroviral (ART) medicines. To
      this end, our laboratory has applied the principles of nanomedicine to simplify
      ART regimens and as such reduce toxicities while improving compliance and drug
      pharmacokinetics. Simple and reliable methods for manufacturing nanoformulated
      ART (nanoART) are shown. Particles of pure drug are encapsulated by a thin layer
      of surfactant lipid coating and produced by fractionating larger drug crystals
      into smaller ones by either wet milling or high-pressure homogenization. In an
      alternative method free drug is suspended in a droplet of a polymer. Herein, drug
      is dissolved within a polymer then agitated by ultrasonication until individual
      nanosized droplets are formed. Dynamic light scattering and microscopic
      examination characterize the physical properties of the particles (particle size,
      charge and shape). Their biologic properties (cell uptake and retention,
      cytotoxicity and antiretroviral efficacy) are determined with human monocyte
      derived macrophages (MDM). MDM are derived from human peripheral blood monocytes
      isolated from leukopacks using centrifugal elutriation for purification. Such
      blood-borne macrophages may be used as cellular transporters for nanoART
      distribution to human immunodeficiency virus (HIV) infected organs. We posit that
      the repackaging of clinically available antiretroviral medications into
      nanoparticles for HIV-1 treatments may improve compliance and positively affect
      disease outcomes.

PMID- 21178969
TI  - Registered bioimaging of nanomaterials for diagnostic and therapeutic monitoring.
AB  - Nanomedications can be carried by blood borne monocyte-macrophages into the
      reticuloendothelial system (RES; spleen, liver, lymph nodes) and to end organs.
      The latter include the lung, RES, and brain and are operative during human
      immunodeficiency virus type one (HIV-1) infection. Macrophage entry into tissues
      is notable in areas of active HIV-1 replication and sites of inflammation. In
      order to assess the potential of macrophages as nanocarriers, superparamagnetic
      iron-oxide and/or drug laden particles coated with surfactants were parenterally
      injected into HIV-1 encephalitic mice. This was done to quantitatively assess
      particle and drug biodistribution. Magnetic resonance imaging (MRI) test results
      were validated by histological coregistration and enhanced image processing. End
      organ disease as typified by altered brain histology were assessed by MRI. The
      demonstration of robust migration of nanoformulations into areas of focal
      encephalitis provides '"proof of concept" for the use of advanced bioimaging
      techniques to monitor macrophage migration. Importantly, histopathological
      aberrations in brain correlate with bioimaging parameters making the general
      utility of MRI in studies of cell distribution in disease feasible. We posit that
      using such methods can provide a real time index of disease burden and
      therapeutic efficacy with translational potential to humans.

PMID- 21178970
TI  - Peptides from phage display library modulate gene expression in mesenchymal cells
      and potentiate osteogenesis in unicortical bone defects.
AB  - Two novel synthetic peptides accelerate bone formation and can be delivered using
      a collagen matrix. The aim of this study was to investigate the effects on bone
      repair in a unicortical defect model. Treatment of mesenchymal cells produced an
      increase in alkaline phosphatase activity, showed nodule formation by the cells,
      and increased the expression of genes for runx2, osterix, bone sialoprotein, and
      osteocalcin. A collagen sponge soaked with peptide promoted repair of bone
      defects, whereas the control was less effective. The results from this study
      demonstrated that mesenchymal cells treated with peptide in vitro differentiate
      towards osteogenesis, and, that peptides delivered in vivo using a collagen
      sponge promote the repair of unicortical defects.

PMID- 21178971
TI  - Fabrication of micro-tissues using modules of collagen gel containing cells.
AB  - This protocol describes the fabrication of a type of micro-tissues called
      modules. The module approach generates uniform, scalable and vascularized
      tissues. The modules can be made of collagen as well as other gelable or
      crosslinkable materials. They are approximately 2 mm in length and 0.7 mm in
      diameter upon fabrication but shrink in size with embedded cells or when the
      modules are coated with endothelial cells. The modules individually are small
      enough that the embedded cells are within the diffusion limit of oxygen and other
      nutrients but modules can be packed together to form larger tissues that are
      perfusable. These tissues are modular in construction because different cell
      types can be embedded in or coated on the modules before they are packed together
      to form complex tissues. There are three main steps to making the modules:
      neutralizing the collagen and embedding cells in it, gelling the collagen in the
      tube and cutting the modules and coating the modules with endothelial cells.

PMID- 21178972
TI  - Preparation of complaint matrices for quantifying cellular contraction.
AB  - The regulation of cellular adhesion to the extracellular matrix (ECM) is
      essential for cell migration and ECM remodeling. Focal adhesions are
      macromolecular assemblies that couple the contractile F-actin cytoskeleton to the
      ECM. This connection allows for the transmission of intracellular mechanical
      forces across the cell membrane to the underlying substrate. Recent work has
      shown the mechanical properties of the ECM regulate focal adhesion and F-actin
      morphology as well as numerous physiological processes, including cell
      differentiation, division, proliferation and migration. Thus, the use of cell
      culture substrates has become an increasingly prevalent method to precisely
      control and modulate ECM mechanical properties. To quantify traction forces at
      focal adhesions in an adherent cell, compliant substrates are used in conjunction
      with high-resolution imaging and computational techniques in a method termed
      traction force microscopy (TFM). This technique relies on measurements of the
      local magnitude and direction of substrate deformations induced by cellular
      contraction. In combination with high-resolution fluorescence microscopy of
      fluorescently tagged proteins, it is possible to correlate cytoskeletal
      organization and remodeling with traction forces. Here we present a detailed
      experimental protocol for the preparation of two-dimensional, compliant matrices
      for the purpose of creating a cell culture substrate with a well-characterized,
      tunable mechanical stiffness, which is suitable for measuring cellular
      contraction. These protocols include the fabrication of polyacrylamide hydrogels,
      coating of ECM proteins on such gels, plating cells on gels, and high-resolution
      confocal microscopy using a perfusion chamber. Additionally, we provide a
      representative sample of data demonstrating location and magnitude of cellular
      forces using cited TFM protocols.

PMID- 21178973
TI  - Isolation and culture of pulmonary endothelial cells from neonatal mice.
AB  - Endothelial cells provide a useful research model in many areas of vascular
      biology. Since its first isolation, human umbilical vein endothelial cells
      (HUVECs) have shown to be convenient, easy to obtain and culture, and thus are
      the most widely studied endothelial cells. However, for research focused on
      processes like angiogenesis, permeability or many others, microvascular
      endothelial cells (ECs) are a much more physiologically relevant model to study.
      Furthermore, ECs isolated from knockout mice provide a useful tool for analysis
      of protein function ex vivo. Several approaches to isolate and culture
      microvascular ECs of different origin have been reported to date, but consistent
      isolation and culture of pure ECs is still a major technical problem in many
      laboratories. Here, we provide a step-by-step protocol on a reliable and
      relatively simple method of isolating and culturing mouse lung endothelial cells
      (MLECs). In this approach, lung tissue obtained from 6- to 8-day old pups is
      first cut into pieces, digested with collagenase/dispase (C/D) solution and
      dispersed mechanically into single-cell suspension. MLECS are purified from cell
      suspension using positive selection with anti-PECAM-1 antibody conjugated to
      Dynabeads using a Magnetic Particle Concentrator (MPC). Such purified cells are
      cultured on gelatin-coated tissue culture (TC) dishes until they become
      confluent. At that point, cells are further purified using Dynabeads coupled to
      anti-ICAM-2 antibody. MLECs obtained with this protocol exhibit a cobblestone
      phenotype, as visualized by phase-contrast light microscopy, and their
      endothelial phenotype has been confirmed using FACS analysis with anti-VE
      cadherin and anti-VEGFR2 antibodies and immunofluorescent staining of VE
      cadherin. In our hands, this two-step isolation procedure consistently and
      reliably yields a pure population of MLECs, which can be further cultured. This
      method will enable researchers to take advantage of the growing number of
      knockout and transgenic mice to directly correlate in vivo studies with results
      of in vitro experiments performed on isolated MLECs and thus help to reveal
      molecular mechanisms of vascular phenotypes observed in vivo.

PMID- 21178974
TI  - Vasopressin-dependent coupling between sodium transport and water flow in a mouse
      cortical collecting duct cell line.
AB  - Water balance is achieved through the ability of the kidney to control water
      reabsorption in the connecting tubule and the collecting duct. In a mouse
      cortical collecting duct cell line (mCCD(c11)), physiological concentrations of
      arginine vasopressin increased both electrogenic, amiloride-sensitive, epithelial
      sodium channel (ENaC)-mediated sodium transport measured by the short-circuit
      current (Isc) method and water flow (Jv apical to basal) measured by gravimetry
      with similar activation coefficient K(1/2) (6 and 12 pM, respectively). Jv
      increased linearly according to the osmotic gradient across the monolayer. A
      small but highly significant Jv was also measured under isoosmotic conditions. To
      test the coupling between sodium reabsorption and water flow, mCCD(c11) cells
      were treated for 24 h under isoosmotic condition with either diluent, amiloride,
      vasopressin or vasopressin and amiloride. Isc, Jv, and net chemical sodium fluxes
      were measured across the same monolayers. Around 30% of baseline and 50% of
      vasopressin-induced water flow is coupled to an amiloride-sensitive, ENaC
      mediated, electrogenic sodium transport, whereas the remaining flow is coupled to
      an amiloride-insensitive, nonelectrogenic sodium transport mediated by an unknown
      electroneutral transporter. The mCCD(c11) cell line is a first example of a
      mammalian tight epithelium allowing quantitative study of the coupling between
      sodium and water transport. Our data are consistent with the 'near isoosmotic'
      fluid transport model.

PMID- 21178975
TI  - Renalase deficiency aggravates ischemic myocardial damage.
AB  - Chronic kidney disease (CKD) leads to an 18-fold increase in cardiovascular
      complications not fully explained by traditional risk factors. Levels of
      renalase, a recently discovered oxidase that metabolizes catecholamines, are
      decreased in CKD. Here we show that renalase deficiency in a mouse knockout model
      causes increased plasma catecholamine levels and hypertension. Plasma blood urea
      nitrogen, creatinine, and aldosterone were unaffected. However, knockout mice had
      normal systolic function and mild ventricular hypertrophy but tolerated cardiac
      ischemia poorly and developed myocardial necrosis threefold more severe than that
      found in wild-type mice. Treatment with recombinant renalase completely rescued
      the cardiac phenotype. To gain insight into the mechanisms mediating this
      cardioprotective effect, we tested if gene deletion affected nitrate and
      glutathione metabolism, but found no differences between hearts of knockout and
      wild-type mice. The ratio of oxidized (NAD) to reduced (NADH) nicotinamide
      adenine dinucleotide in cardiac tissue, however, was significantly decreased in
      the hearts of renalase knockout mice, as was plasma NADH oxidase activity. In
      vitro studies confirmed that renalase metabolizes NADH and catecholamines. Thus,
      renalase plays an important role in cardiovascular pathology and its replacement
      may reduce cardiac complications in renalase-deficient states such as CKD.

PMID- 21178976
TI  - Protein-energy wasting modifies the association of ghrelin with inflammation,
      leptin, and mortality in hemodialysis patients.
AB  - Ghrelin abnormalities contribute to anorexia, inflammation, and cardiovascular
      risk in hemodialysis patients, leading to worse outcome. However, ghrelin levels
      are influenced by the nutritional status of the individual. We hypothesized that
      the consequences of ghrelin alterations in hemodialysis patients are context
      sensitive and dependent on the presence of protein-energy wasting (PEW). In this
      cross-sectional study of 217 prevalent hemodialysis patients followed for 31
      months, we measured ghrelin, leptin, PEW (subjective global assessment), and C
      reactive protein (an index of inflammation). Compared to patients in the middle
      and upper tertile of ghrelin levels, those in the lowest tertile were older, had
      higher leptin levels and body mass index, and presented an increased mortality
      risk that persisted after adjustment for age, gender, and dialysis vintage. This
      risk was lost after correction for comorbidities. Patients with PEW and low
      ghrelin values had abnormally high C-reactive protein and leptin by multivariate
      analysis of variance, and the highest mortality risk compared to non-PEW with
      high ghrelin from all-cause and cardiovascular-related mortality (adjusted hazard
      ratios of 3.34 and 3.54, respectively). Low ghrelin values in protein-energy
      wasted hemodialysis patients were linked to a markedly increased cardiovascular
      mortality risk. Thus, since these patients were more anorectic, our results
      provide a clinical scenario where ghrelin therapies may be particularly useful.

PMID- 21178978
TI  - Focal segmental glomerulosclerosis plays a major role in the progression of IgA
      nephropathy. II. Light microscopic and clinical studies.
AB  - It is well known that lesions morphologically identical with focal segmental
      glomerulosclerosis (FSGS) may appear in IgA nephropathy (IgAN). Capsular
      adhesions without underlying abnormalities in the tuft, often the first sign of
      FSGS, are frequent in IgAN. In this retrospective study, a new cohort of 128
      adult patients with IgAN was used to validate the new Oxford classification
      system of IgAN, and shown to have highly significant associations with clinical
      and outcome parameters. We then used these patients to determine the extent to
      which IgAN could be accounted for in terms of FSGS. Some form of lesion
      consistent with FSGS, notably hyalinosis and collapsing glomerulopathy, was found
      in 101 of these patients. No glomerular lesions were found in 16 patients, and 11
      had mild lesions not definable as FSGS. Those with FSGS had significantly worse
      renal survival at 80 months than those without. Comparison of pure forms of FSGS
      (excluding collapsing glomerulopathy) with cases of FSGS having other glomerular
      lesions (mesangial hyperplasia, endocapillary hypercellularity, glomerular
      necroses, extracapillary proliferation) revealed that those with FSGS and other
      superimposed lesions did significantly worse than cases of pure FSGS at 80 months
      following diagnosis. Importantly, patients with pure FSGS had relatively poor
      survival even without other superimposed glomerular abnormalities. Thus, the
      majority of cases of IgAN can be interpreted as representing one or another
      variant of FSGS. Hence, interpreting IgAN in terms of FSGS emphasizes the role
      that podocyte lesions may play in the pathogenesis and progression of this
      disease.

PMID- 21178977
TI  - Clinical trials treating focal segmental glomerulosclerosis should measure
      patient quality of life.
AB  - Optimal therapy of patients with steroid-resistant primary focal segmental
      glomerulosclerosis (FSGS) remains controversial. This report describes the
      initial study design, baseline characteristics, and quality of life of patients
      enrolled in the FSGS Clinical Trial, a large multicenter randomized study of this
      glomerulopathy comparing a 12-month regimen of cyclosporine to the combination of
      mycophenolate mofetil and oral dexamethasone. Patients with age ranging 2-40
      years, with an estimated glomerular filtration rate > 40 ml/min per 1.73 m2, a
      first morning urine protein-to-creatinine ratio over one, and resistant to
      corticosteroids were eligible. The primary outcome was complete or partial
      remission of proteinuria over 52 weeks after randomization. In all, 192 patients
      were screened, of whom 138 were randomized for treatment. Ethnic distributions
      were 53 black, 78 white, and 7 other. By self- or parent-proxy reporting, 26 of
      the 138 patients were identified as Hispanic. The baseline glomerular filtration
      rate was 112.4 (76.5, 180.0) ml/min per 1.73 m2, and urine protein was 4.0 (2.1,
      5.3) g/g. Overall, the quality of life of the patients with FSGS was lower than
      healthy controls and similar to that of patients with end-stage renal disease.
      Thus, the impact of FSGS on quality of life is significant and this measurement
      should be included in all trials.

PMID- 21178979
TI  - Prevention and management of catheter-related infection in hemodialysis patients.
AB  - Central venous catheter-related infections have been associated with high
      morbidity, mortality, and costs. Catheter use in chronic hemodialysis patients
      has been recognized as distinct from other patient populations who require
      central venous access, leading to recent adaptations in guidelines-recommended
      diagnosis for catheter-related bacteremia (CRB). This review will discuss the
      epidemiology and pathogenesis of hemodialysis CRB, in addition to a focus on
      interventions that have favorably affected CRB outcomes. These include: (1) the
      use of prophylactic topical antimicrobial ointments at the catheter exit site,
      (2) the use of prophylactic catheter locking solutions for the prevention of CRB,
      (3) strategies for management of the catheter in CRB, and (4) the use of vascular
      access managers and quality initiative programs.

PMID- 21178980
TI  - Abdominal obesity modifies the risk of hypertriglyceridemia for all-cause and
      cardiovascular mortality in hemodialysis patients.
AB  - Hypertriglyceridemia is the most prevalent lipid alteration in end-stage renal
      disease, and we studied the relationship between serum triglycerides and all
      cause and cardiovascular death in these patients. Since abdominal fat modifies
      the effect of lipids on atherosclerosis, we analyzed the interaction between
      serum lipids and waist circumference (WC) as a metric of abdominal obesity. In a
      cohort of 537 hemodialysis patients, 182 died, 113 from cardiovascular causes,
      over an average follow-up of 29 months. In Cox models that included traditional
      and nontraditional risk factors, there were significant strong interactions
      between triglycerides and WC to both all-cause and cardiovascular death. A fixed
      (50 mg/dl) excess in triglycerides was associated with a progressive lower risk
      of all-cause and cardiovascular mortality in patients with threshold WC <95 cm
      but with a progressive increased risk in those above this threshold. A
      significant interaction between cholesterol and WC with all-cause and
      cardiovascular death emerged only in models excluding the triglycerides-WC
      interaction. Neither high-density lipoprotein (HDL) nor non-HDL cholesterol or
      their interaction terms with WC were associated with study outcomes. Thus, the
      predictive value of triglycerides and cholesterol for survival and
      atherosclerotic complications in hemodialysis patients is critically dependent on
      WC. Hence, intervention studies in end-stage renal disease should specifically
      target patients with abdominal obesity and hyperlipidemia.

PMID- 21178981
TI  - Early adolescence as a critical window during which social stress distinctly
      alters behavior and brain norepinephrine activity.
AB  - Many neural programs that shape behavior become established during adolescence.
      Adverse events at this age can have enduring consequences for both adolescent and
      adult mental health. Here we show that repeated social stress at different stages
      of adolescent development differentially affects rat behavior and neuronal
      activity. Early-adolescent (PND 28, EA), mid-adolescent (PND 42, MA), and adult
      (PND 63) rats were subjected to resident-intruder social stress (7 days) and
      behavior was examined 24-72 h later. In EA rats selectively, resident-intruder
      stress increased proactive responses in the defensive burying and forced swim
      tests. In adult rats, resident-intruder stress decreased burying behavior
      regardless of whether the animal was stressed as an adult or during early
      adolescence. As the locus coeruleus (LC)-norepinephrine system has been
      implicated in proactive defense behaviors, LC neuronal activity was quantified in
      separate cohorts. Stressed EA rats had elevated spontaneous LC discharge rates
      and diminished responses to sensory stimuli compared with controls.
      Microinjection of a CRF antagonist into the LC selectively inhibited neurons of
      stressed EA rats, suggesting that EA social stress induces tonic CRF release onto
      LC neurons, shifting the mode of discharge to an activated state that promotes
      active defensive behaviors. In all adult groups, resident-intruder stress
      resulted in an increased phasic response to sensory stimuli with no change in
      spontaneous rates. MA was a transition period during which social stress did not
      affect behavior or LC activity. The results suggest that social stress interacts
      with the brain norepinephrine system to regulate defensive strategies in an age
      dependent manner.

PMID- 21178982
TI  - In vivo binding of antipsychotics to D3 and D2 receptors: a PET study in baboons
      with [11C]-(+)-PHNO.
AB  - Measuring the in vivo occupancy of antipsychotic drugs at dopamine D(2) and D(3)
      receptors separately has been difficult because of the lack of selective
      radiotracers. The recently developed [(11)C]-(+)-PHNO is D(3)-preferring,
      allowing estimates of the relative D(2) and D(3) binding of antipsychotic drugs.
      We used positron emission tomography (PET) imaging in baboons with [(11)C]-(+)
      PHNO to examine the binding of clozapine and haloperidol to D(2) and D(3)
      receptors. Four animals were scanned with dynamically acquired PET and arterial
      plasma input functions. Test and retest scans were acquired in single scanning
      sessions for three subjects to assess the reproducibility of [(11)C]-(+)-PHNO
      scans. Four additional scans were acquired in each of three subjects following
      single doses of antipsychotic drugs (clozapine 0.5534 mg/kg, haloperidol 0.0109
      mg/kg, two administrations per drug per subject) and compared with baseline
      scans. The percent change in binding (DeltaBP(ND)) following challenges with
      antipsychotic drugs was measured. A regression model, based on published values
      of regional D(2) and D(3) fractions of [(11)C]-(+)-PHNO BP(ND) in six brain
      regions, was used to infer occupancy at D(2) and D(3) receptors. BP(ND) following
      antipsychotic challenge decreased in all regions. Estimated D(2) : D(3)
      selectivity was 2.38 for haloperidol and 5.25 for clozapine, similar to published
      in vitro values for haloperidol (3.03), but slightly higher for clozapine (2.82).
      These data suggest that acute doses of clozapine and haloperidol bind to D(3)
      receptors in vivo, and that the lack of D(3) occupancy by antipsychotics observed
      in some recent imaging studies may be because of other phenomena.

PMID- 21178983
TI  - Homeostatic control of conjunctival mucosal goblet cells by NKT-derived IL-13.
AB  - Although the effects of the interleukin 13 (IL-13) on goblet cell (GC)
      hyperplasia have been studied in the gut and respiratory tracts, its effect on
      regulating conjunctival GC has not been explored. The purpose of this study was
      to determine the major IL-13-producing cell type and the role of IL-13 in GC
      homeostasis in normal murine conjunctiva. Using isolating techniques, we
      identified natural killer (NK)/natural killer T (NKT) cells as the main producers
      of IL-13. We also observed that IL-13 knockout (KO) and signal transducer and
      activator of transcription 6 knockout (STAT6KO) mice had a lower number of
      periodic acid Schiff (PAS)+GCs. We observed that desiccating stress (DS)
      decreases NK population, GCs, and IL-13, whereas it increases interferon-gamma
      (IFN-gamma) mRNA in conjunctiva. Cyclosporine A treatment during DS maintained
      the number of NK/NKT cells in the conjunctiva, increased IL-13 mRNA in NK+ cells,
      and decreased IFN-gamma and IL-17A mRNA transcripts in NK+ and NK- populations.
      C57BL/6 mice chronically depleted of NK/NKT cells, as well as NKT cell-deficient
      RAG1KO and CD1dKO mice, had fewer filled GCs than their wild-type counterparts.
      NK depletion in CD1dKO mice had no further effect on the number of PAS+ cells.
      Taken together, these findings indicate that NKT cells are major sources of IL-13
      in the conjunctival mucosa that regulates GC homeostasis.

PMID- 21178984
TI  - Histamine: new thoughts about a familiar mediator.
AB  - Any health-care provider knows that the sneezing, wheezing, and itching that are
      commonplace most often involve a small molecule, namely, histamine. In addition
      to its inherent physiologic role, this seemingly small "actor" is of profound
      historical and fiscal significance. This is evidenced in part by the awarding of
      the 1936 Nobel Prize in physiology or Medicine to Sir Henry Hallett Dale and Dr
      Otto Loewi who discovered the actions of histamine and the 1957 Nobel Prize in
      physiology or medicine to pharmacologist Dr Daniel Bovet who discovered the first
      antihistamine, pyrilamine (neoantergan)(1). (see Supplementary Data for full
      reference).

PMID- 21178986
TI  - Differential impacts of CYP2C19 gene polymorphisms on the antiplatelet effects of
      clopidogrel and ticlopidine.
AB  - We examined the influence of CYP2C19 polymorphisms on the antiplatelet effects of
      clopidogrel and ticlopidine. The platelet aggregation induced by 20 umol/l
      adenosine diphosphate (ADP) and CYP2C19 single-nucleotide polymorphisms (*2 and
      *3) was determined in patients with coronary artery disease (CAD) who were taking
      aspirin alone (n = 21), aspirin plus clopidogrel (n = 97), or aspirin plus
      ticlopidine (n = 47). The degree of platelet aggregation in the clopidogrel
      group, although not in the ticlopidine group, depended on the CYP2C19
      polymorphism, and the maximal platelet aggregation in poor metabolizers (PMs)
      taking clopidogrel was equivalent to that in the group taking aspirin alone.
      After being switched from clopidogrel to ticlopidine, all seven of the PMs showed
      markedly lower platelet aggregation. These results suggest that CYP2C19
      polymorphisms have a profound impact on the antiplatelet effect of clopidogrel
      but not on that of ticlopidine. Ticlopidine may be an effective therapeutic
      option for CYP2C19 PMs.

PMID- 21178987
TI  - Current challenges with supply-chain integrity and the threat to the quality of
      marketed drugs.

PMID- 21178985
TI  - Common nonsynonymous substitutions in SLCO1B1 predispose to statin intolerance in
      routinely treated individuals with type 2 diabetes: a go-DARTS study.
AB  - SLCO1B1 gene variants are associated with severe statin-induced myopathy. We
      examined whether these variants are also associated with general statin
      intolerance in a large population of patients with type 2 diabetes receiving
      statins as part of routine clinical care. A total of 4,196 individuals were
      genotyped for rs4149056 (Val174Ala) and rs2306283 (Asp130Asn). Intolerance was
      defined by serum biochemistry and also by discontinuation, switching, or
      reduction in dose of the prescribed statin drug. Ala174 was associated with
      higher intolerance (odds ratio = 2.05, P = 0.043), whereas Asp130 was associated
      with lower intolerance (odds ratio = 0.71, P = 0.026). Ala174 was associated with
      a lower low-density lipoprotein cholesterol (LDLc) response to statins (P = 0.01)
      whereas 130D was associated with a greater LDLc response to statins (P = 0.048),
      as previously reported; however, this association was no longer present when data
      for statin-intolerant individuals were removed from the analysis. This study
      suggests that common genetic variants selected for an extreme phenotype of statin
      induced myopathy also predispose to more common milder statin intolerance and
      may, for this reason, impact lipid-lowering efficacy.

PMID- 21178988
TI  - Portfolio selection and management in pharmaceutical research and development:
      issues and challenges.

PMID- 21178989
TI  - A randomized, placebo-controlled trial of sustained-release dextroamphetamine for
      treatment of methamphetamine addiction.
AB  - Sixty treatment-seeking individuals with methamphetamine (MA) dependence entered
      a randomized, placebo-controlled, double-blind clinical trial of oral
      dextroamphetamine (d-AMP) as a replacement therapy for MA dependence. The
      subjects took 60 mg sustained-release d-AMP for 8 weeks, during which time they
      received eight 50-min sessions of individual psychotherapy. Adverse events and
      urine toxicology for MA were assessed two times a week. There were no serious
      adverse events. Urine samples containing <1,000 ng/ml of MA were classified as
      negative for MA. The MA-negative scores in the d-AMP group (3.1 +/- SD 4.6) were
      no higher than those in the placebo group (3.3 +/- SD 5.3; P > 0.05). However,
      withdrawal and craving scores were significantly lower in the d-AMP group (P <
      0.05 for both). Although subjects taking d-AMP did not reduce their use of MA,
      the significant reductions observed in withdrawal and craving scores in this
      group support the need for further exploration of d-AMP as a pharmacologic
      intervention for MA dependence, possibly at higher doses.

PMID- 21178991
TI  - What constitutes an optimal portfolio of pharmaceutical compounds?

PMID- 21178990
TI  - Application of the BRAT framework to case studies: observations and insights.
AB  - The BRAT Framework is a set of flexible processes and tools that provides a
      structured approach to pharmaceutical benefit-risk decision making in drug
      development and post approval settings. A work in progress, it consists of six
      steps that produce representations of key tradeoffs, with appropriate
      documentation of the rationale for decisions and the assumptions made in their
      development. This article describes insights, gained from case studies, into the
      Framework's performance in a variety of constructed benefit-risk scenarios,
      focusing on a hypothetical example of a triptan for migraine. The scenarios
      described illustrate the challenges inherent in arriving at many of the
      regulatory decisions, including obtaining data for matching populations for all
      outcomes, finding data of consistent quality, addressing correlated outcomes
      (e.g., elevated liver function tests and hepatitis rates), dealing with rare but
      serious adverse events (AEs), and understanding and making decisions based on
      information for many outcomes simultaneously. The Framework provides a structure
      for organizing, interpreting, and communicating relevant information, including
      heterogeneity in results and the quality and level of uncertainty of data, in
      order to facilitate benefit-risk decisions.

PMID- 21178992
TI  - Changes to ICH guideline M3: new and revised guidance on nonclinical safety
      studies to support human clinical trials and marketing authorization.

PMID- 21178993
TI  - Clinical value, normative retinal sensitivity values, and intrasession
      repeatability using a combined spectral domain optical coherence
      tomography/scanning laser ophthalmoscope microperimeter.
AB  - PURPOSE: To establish normative values for macular light sensitivity and to
      determine the intrasession fluctuation of perimetric responses using the OPKO/OTI
      microperimeter. METHODS: A total of 32 visually normal subjects participated in
      the study. A standardized grid pattern was used for testing, which consisted of
      28 points arranged concentrically in three circles that occupied an area of 11
      degrees  (in diameter) within the central macula. Each subject participated in at
      least two tests. Parameters evaluated included: overall mean macular sensitivity
      for test 1 and 2, overall difference in mean macular sensitivity between tests,
      and the mean sensitivity for each circle. The relationship between sensitivity
      and age was also examined. RESULTS: The overall median sensitivity for test 1 was
      16.8 decibels (dB) and for test 2 was 16.9 dB. The median sensitivities for test
      1 and test 2 were not significantly different (P = 0.72). The mean intrasession
      sensitivity difference was 0.13 dB. The variability of the sensitivity difference
      between tests decreased as mean sensitivity increased. The sensitivity values
      averaged across the two tests for inner, middle, and outer circles ranged from
      14.3 to 18.8 dB (median value of 16.9 dB), 13.8-18.3 dB (median value of 17.2
      dB), and 11.3-18.3 dB (median value of 16.6 dB), respectively. Linear regression
      analysis showed a 0.5 dB sensitivity loss for each decade of life. CONCLUSION: We
      documented a narrow range of intrasession fluctuation using the OPKO/OTI
      microperimeter. The establishment of normative sensitivity values will facilitate
      monitoring the loss of macular visual function in patients with retinal disease.

PMID- 21178994
TI  - Accidental self-induced chemical eye injury in patients with low vision.

PMID- 21178996
TI  - Addisonian crisis in a young man with atypical anorexia nervosa.
AB  - BACKGROUND: A 22-year-old man was admitted to an intensive care unit with severe
      hyponatremia, hypotension and somnolence. He had a 9-month history of weight loss
      and vomiting that had led to a previous diagnosis of atypical anorexia, and he
      had been transferred from a psychiatric clinic. INVESTIGATIONS: Generalized
      hyperpigmentation and dehydration were noted on physical examination. Baseline
      concentrations of plasma adrenocorticotropic hormone, serum cortisol, plasma
      renin and serum aldosterone were analyzed. Determination of antibodies against
      adrenal steroid 21-hydroxylase, measurement of very-long-chain fatty acids and
      thyroid function tests were performed. DIAGNOSIS: Primary adrenal insufficiency
      caused by isolated autoimmune adrenalitis and adrenal crisis. MANAGEMENT:
      Immediate administration of hydrocortisone (100 mg bolus dose followed by 100 mg
      over 24 h per continuous infusion) and physiological saline infusions (initially
      4 l over 24 h). After stabilization, initiation of chronic hormone replacement
      therapy with hydrocortisone (initially 30 mg per day) and fludrocortisone (0.1 mg
      daily). The patient was instructed on how to adjust hydrocortisone doses in
      stressful situations and provided with an emergency card.

PMID- 21178995
TI  - Retinal light toxicity.
AB  - The ability of light to enact damage on the neurosensory retina and underlying
      structures has been well understood for hundreds of years. While the eye has
      adapted several mechanisms to protect itself from such damage, certain exposures
      to light can still result in temporal or permanent damage. Both clinical
      observations and laboratory studies have enabled us to understand the various
      ways by which the eye can protect itself from such damage. Light or
      electromagnetic radiation can result in damage through photothermal,
      photomechanical, and photochemical mechanisms. The following review seeks to
      describe these various processes of injury and many of the variables, which can
      mitigate these modes of injury.

PMID- 21178998
TI  - Fetal microchimerism as an explanation of disease.
AB  - Fetal cell microchimerism is defined as the persistence of fetal cells in the
      mother after birth without any apparent rejection. Fetal microchimeric cells
      (FMCs) engraft into the maternal bone marrow for decades after delivery and are
      able to migrate to blood and tissues. This phenomenon was hypothesized to have a
      detrimental role in autoimmune diseases, but data are still controversial and
      debated. In malignant tumors, fetal cell microchimerism has been postulated to
      have a positive effect on tumor burden, although some evidence suggests that FMCs
      may be involved in neoplastic progression. At the peripheral level, circulating
      FMCs are less frequently detected in patients with thyroid cancer, breast cancer
      or other solid, hematologic malignancies than in healthy individuals, which
      suggests a protective role for fetal cell microchimerism. In tissues, FMCs have
      been found in tumor sections from malignancies such as thyroid, breast, cervix,
      lung cancers and melanomas and have been shown to differentiate into epithelial,
      hematopoietic, endothelial and mesenchymal cells. FMCs with hematopoietic
      differentiation have been postulated to have a role in destroying the tumor,
      whereas mesenchymal and epithelial cells could participate in repair processes.
      Endothelial cells, on the other hand, are believed to play a part in tumor
      progression. This Review provides an overview of the role of fetal cell
      microchimerism in autoimmune and benign or malignant nonautoimmune diseases.
      Moreover, the mechanisms by which fetal cell microchimerism is believed to
      modulate the protection against cancer or tumor progression will be discussed,
      together with future research directions.

PMID- 21178999
TI  - Neoadjuvant radiotherapy for locally advanced and high-risk prostate cancer.
AB  - Men presenting with high-risk or locally advanced prostate cancer may benefit
      from a combination of radiotherapy and surgery to maximize local control.
      Adjuvant radiotherapy following surgery has improved biochemical progression-free
      survival, metastasis-free survival, lengthened the time to hormone therapy use
      and improved overall survival in three randomized-phase III trials. One
      surprising result of the Southwest Oncology Group (SWOG) 8794 trial and the
      European Organisation for Research and Treatment of Cancer (EORTC) 22911 trial is
      that treatment failure was mainly a result of lack of local control. This finding
      has led to a new appreciation of local control as a determinant of survival and
      the role for combined modality approaches within a multidisciplinary team in the
      treatment of high-risk and locally advanced prostate cancer. One emerging novel
      approach is the use of preoperative or intraoperative radiotherapy in addition to
      best surgical and systemic treatments. Preliminary results from clinical trials
      indicate low rates of intraoperative toxic effects, an advantage of short
      treatment times and smaller image-guided radiotherapy treatment volumes when
      compared with postoperative radiotherapy. Potential disadvantages include over
      treatment of patients and lack of data on long-term toxic effects. We present the
      published treatment approaches and rational for preoperative and intraoperative
      radiotherapy and compare these methods to the utility of postoperative
      radiotherapy.

PMID- 21178997
TI  - Prospective influences of circadian clocks in adipose tissue and metabolism.
AB  - Circadian rhythms make a critical contribution to endocrine functions that
      involve adipose tissue. These contributions are made at the systemic, organ and
      stem cell levels. The transcription factors and enzymes responsible for the
      maintenance of circadian rhythms in adipose depots and other peripheral tissues
      that are metabolically active have now been identified. Furthermore, the
      circadian regulation of glucose and lipid metabolism is well-established. Animal
      and human models provide strong evidence that disturbances in circadian pathways
      are associated with an increased risk of type 2 diabetes mellitus, obesity and
      their comorbidities. Thus, circadian mechanisms represent a novel putative target
      for therapy in patients with metabolic diseases.

PMID- 21179001
TI  - Combined amylin-leptin treatment lowers blood pressure and adiposity in lean and
      obese rats.
AB  - OBJECTIVE: To examine the cardiovascular effects of combined amylin (AMN) and
      leptin (LEP) treatment in lean and obese rats. RESEARCH DESIGN: Rats were
      instrumented for telemetry and given LEP (300 MUg kg(-1) day(-1)), AMN (100 MUg
      kg(-1) day(-1)), AMN+LEP or vehicle (VEH; 0.9% normal saline) via a subcutaneous
      mini-osmotic pump for 7 days. The VEH group was subdivided into ad libitum fed
      and pair-fed to the amount of food AMN+LEP animals ate daily. Rats were housed in
      metabolic chambers for analysis of cardiovascular physiology and metabolism.
      SUBJECTS: Male Fisher 344 * Brown Norway (FBNF1; Harlan; age=3-5 months; n=72)
      rats were placed on standard rodent chow (LEAN, n=41) or moderately high-fat diet
      (OBESE; n=31) to produce obesity. RESULTS: AMN+LEP potently reduced food intake
      (LEAN: 57% OBESE: 59%) and abdominal fat mass (LEAN: 56% OBESE: 41%). Pair-fed
      rats displayed bradycardia and metabolic suppression. In contrast, AMN+LEP
      increased heart rate and oxygen consumption above levels in LEP or AMN-treated
      rats. LEP reduced blood pressure in both lean and obese rats but AMN had no
      effect. LEP-induced reductions in blood pressure were not altered by AMN+LEP
      treatment. Thus, AMN+LEP treatment decreased food intake, body fat and blood
      pressure in lean and obese rats. CONCLUSION: We conclude that the potent anti
      adiposity actions of AMN+LEP are due in part to prevention of the bradycardia and
      metabolic suppression typically observed with negative energy balance.
      Furthermore, the hypotensive actions of peripheral LEP treatment are observable
      in spite of the potent AMN+LEP activation of anorexic and thermogenic mechanisms
      in the central nervous system.

PMID- 21179003
TI  - Association between fat intake, physical activity and mortality depending on
      genetic variation in FTO.
AB  - OBJECTIVE: We wanted to explore if FTO genotype interacts with fat intake, or
      leisure-time physical activity, on fat mass, lean mass and mortality. SUBJECTS
      AND METHODS: Among 22,799 individuals (44-74 years) in the population-based Malmo
      diet and cancer cohort that were genotyped for rs9939609 in FTO and had
      information on dietary intake (from a modified diet history method) and no
      history of diabetes, cancer or cardiovascular disease, 2255 deaths (including
      1100 cancer and 674 cardiovascular deaths) occurred during 12.0 years of follow
      up. Leisure-time physical activity was determined from a list of 17 different
      physical activities in a questionnaire. Body composition was measured using
      bioelectric impedance method. RESULTS: FTO genotype associated strongly with both
      fat mass and lean mass (P(trend) <1 * 10(-16) for both) but we found only
      significant interactions with fat intake, or physical activity, on fat mass
      (P(interaction)=0.01 and 0.004). No significant interaction between FTO genotype
      and fat intake (P(interaction)=0.72), or leisure-time physical activity
      (P(interaction)=0.07), on total mortality were observed. However, we observed a
      significant interaction between leisure-time physical activity and FTO genotype
      on cardiovascular mortality (P(interaction)=0.03). The highest vs lowest quintile
      of physical activity was associated with 46% (95% confidence interval, 17-64%)
      reduced cardiovascular mortality among TT-carriers (P(trend)=0.004), and 11%
      reduced cardiovascular mortality among A-allele carriers (P(trend)=0.68).
      CONCLUSION: Our results indicate that FTO genotype associates with both fat mass
      and lean mass, but the level of fat intake and physical activity only modify the
      association with fat mass. In addition, FTO genotype may modify the association
      between physical activity and cardiovascular mortality.

PMID- 21179000
TI  - Reproducibility of glucose, fatty acid and VLDL kinetics and multi-organ insulin
      sensitivity in obese subjects with non-alcoholic fatty liver disease.
AB  - OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is associated with
      abnormalities in basal glucose and free fatty acid (FFA) metabolism, multi-organ
      insulin resistance and alterations in lipoprotein kinetics. These metabolic
      outcomes can be evaluated in vivo by using stable isotopically labeled tracer
      methods. An understanding of the reproducibility of these measures is necessary
      to ensure adequate statistical power in studies designed to evaluate metabolic
      function in subjects with NAFLD. METHODS: We determined the degree of intra
      individual variability of skeletal muscle, adipose tissue, and hepatic insulin
      sensitivity and basal plasma glucose, FFA, and very-low-density lipoprotein
      triglyceride and apolipoprotein B-100 (apoB-100) kinetics in eight obese subjects
      with NAFLD (age: 44 +/- 3 years; body mass index: 38.2 +/- 1.7 kg m(-2);
      intrahepatic triglyceride content: 24.5 +/- 3.9%), by using the hyperinsulinemic
      euglycemic clamp technique and stable isotope-labeled tracer methods and
      mathematical modeling on two separate occasions ~2 months apart. RESULTS: The
      intra-individual variability (coefficient of variation) ranged from 6% for basal
      glucose production to 21% for insulin-stimulated glucose disposal (percentage
      increase from basal). We estimated that a 25% difference in any outcome measure
      can be detected with a sample size of <= 8 subjects for paired studies and <= 15
      subjects per group for unpaired studies, assuming an alpha value of 0.05 and a
      beta value of 0.20 (that is, 80% power). CONCLUSION: These results demonstrate
      that only a small number of subjects are needed to detect clinically relevant
      effects in insulin sensitivity and hepatic lipoprotein metabolism in obese
      subjects with NAFLD, and will be useful to determine appropriate sample size for
      future metabolic studies.

PMID- 21179004
TI  - Differential genomic targeting of the transcription factor TAL1 in alternate
      haematopoietic lineages.
AB  - TAL1/SCL is a master regulator of haematopoiesis whose expression promotes
      opposite outcomes depending on the cell type: differentiation in the erythroid
      lineage or oncogenesis in the T-cell lineage. Here, we used a combination of ChIP
      sequencing and gene expression profiling to compare the function of TAL1 in
      normal erythroid and leukaemic T cells. Analysis of the genome-wide binding
      properties of TAL1 in these two haematopoietic lineages revealed new insight into
      the mechanism by which transcription factors select their binding sites in
      alternate lineages. Our study shows limited overlap in the TAL1-binding profile
      between the two cell types with an unexpected preference for ETS and RUNX motifs
      adjacent to E-boxes in the T-cell lineage. Furthermore, we show that TAL1
      interacts with RUNX1 and ETS1, and that these transcription factors are
      critically required for TAL1 binding to genes that modulate T-cell
      differentiation. Thus, our findings highlight a critical role of the cellular
      environment in modulating transcription factor binding, and provide insight into
      the mechanism by which TAL1 inhibits differentiation leading to oncogenesis in
      the T-cell lineage.

PMID- 21179005
TI  - Asf1b, the necessary Asf1 isoform for proliferation, is predictive of outcome in
      breast cancer.
AB  - Mammalian cells possess two isoforms of the histone H3-H4 chaperone anti
      silencing function 1 (Asf1), Asf1a and Asf1b. However to date, whether they have
      individual physiological roles has remained elusive. Here, we aim to elucidate
      the functional importance of Asf1 isoforms concerning both basic and applied
      aspects. First, we reveal a specific proliferation-dependent expression of human
      Asf1b unparalleled by Asf1a. Strikingly, in cultured cells, both mRNA and protein
      corresponding to Asf1b decrease upon cell cycle exit. Depletion of Asf1b severely
      compromises proliferation, leads to aberrant nuclear structures and a distinct
      transcriptional signature. Second, a major physiological implication is found in
      the applied context of tissue samples derived from early stage breast tumours in
      which we examined Asf1a/b levels. We reveal that overexpression of Asf1b mRNA
      correlate with clinical data and disease outcome. Together, our results highlight
      a distribution of tasks between the distinct Asf1 isoforms, which emphasizes a
      specialized function of Asf1b required for proliferation capacity. We discuss the
      implications of these results for breast cancer diagnosis and prognosis.

PMID- 21179006
TI  - Dysregulated gene expression during hematopoietic differentiation from human
      embryonic stem cells.
AB  - The generation of hematopoietic cells from human embryonic stem cells (hESC) has
      raised the possibility of using hESC as an alternative donor source for
      transplantation. However, functional defects identified in hESC-derived cells
      limit their use for full lymphohematopoietic reconstitution. The purpose of the
      present study was to define and quantitate key functional and molecular
      differences between CD34(+) hematopoietic progenitor subsets derived from hESC
      and CD34(+) subsets from umbilical cord blood (UCB) representing definitive
      hematopoiesis. Two distinct sub-populations were generated following mesodermal
      differentiation from hESC, a CD34(bright) (hematoendothelial) and CD34(dim)
      (hematopoietic-restricted) subset. Limiting dilution analysis revealed profound
      defects in clonal proliferation relative to UCB particularly in B lymphoid
      conditions. Transcription factors normally expressed at specific commitment
      stages during B lymphoid development from UCB-CD34(+) cells were aberrantly
      expressed in hESC-derived CD34(+) cells. Moreover, strong negative regulators of
      lymphopoiesis such as the adaptor protein LNK and CCAAT/enhancer-binding protein
      alpha (CEBPalpha), were exclusively expressed in hESC-CD34(+) subsets. Knockdown
      of LNK lead to an increase in hematopoietic progenitors generated from hESCs. The
      aberrant molecular profile seen in hESC-CD34(+) cells represents persistence of
      transcripts first expressed in undifferentiated hESC and/or CD326-CD56(+)
      mesoderm progenitors, and may contribute to the block in definitive hematopoiesis
      from hESC.

PMID- 21179007
TI  - One-year treatment of morpholino antisense oligomer improves skeletal and cardiac
      muscle functions in dystrophic mdx mice.
AB  - Antisense therapy has been successful to skip targeted dystrophin exon with
      correction of frameshift and nonsense mutations of Duchenne muscular dystrophy
      (DMD). Systemic production of truncated but functional dystrophin proteins has
      been achieved in animal models. Furthermore, phase I/II clinical trials in United
      Kingdom and the Netherlands have demonstrated dystrophin induction by local and
      systemic administrations of antisense oligomers. However, long-term efficacy and
      potential toxicity remain to be determined. The present study examined 1-year
      systemic effect of phosphorodiamidate morpholino oligomers (PMO) treatment
      targeting mutated dystrophin exon 23 in mdx mice. PMO induced dystrophin
      expression dose-dependently and significantly improved skeletal muscle pathology
      and function with reduced creatine kinase (CK) levels by a regimen of 60 mg/kg
      biweekly administration. This regimen induced <2% dystrophin expression in the
      heart, but improved cardiac functions demonstrated by hemodynamics analysis. The
      results suggest that low levels of dystrophin induction may be able to provide
      detectable benefit to cardiac muscle with limited myopathy. Body weight, serum
      enzyme tests, and histology analysis showed no sign of toxicity in the mice
      treated with up to 1.5 g/kg PMO for 6 months. These results indicate that PMO
      could be used safely as effective drugs for long-term systemic treatment of DMD.

PMID- 21179008
TI  - Mechanistically probing lipid-siRNA nanoparticle-associated toxicities identifies
      Jak inhibitors effective in mitigating multifaceted toxic responses.
AB  - A major hurdle for harnessing small interfering RNA (siRNA) for therapeutic
      application is an effective and safe delivery of siRNA to target tissues and
      cells via systemic administration. While lipid nanoparticles (LNPs) composed of a
      cationic lipid, poly-(ethylene glycol) lipid and cholesterol, are effective in
      delivering siRNA to hepatocytes via systemic administration, they may induce
      multi-faceted toxicities in a dose-dependent manner, independently of target
      silencing. To understand the underlying mechanism of toxicities, pharmacological
      probes including anti-inflammation drugs and specific inhibitors blocking
      different pathways of innate immunity were evaluated for their abilities to
      mitigate LNP-siRNA-induced toxicities in rodents. Three categories of rescue
      effects were observed: (i) pretreatment with a Janus kinase (Jak) inhibitor or
      dexamethasone abrogated LNP-siRNA-mediated lethality and toxicities including
      cytokine induction, organ impairments, thrombocytopenia and coagulopathy without
      affecting siRNA-mediated gene silencing; (ii) inhibitors of PI3K, mammalian
      target of rapamycin (mTOR), p38 and IkappaB kinase (IKK)1/2 exhibited a partial
      alleviative effect; (iii) FK506 and etoricoxib displayed no protection.
      Furthermore, knockout of Jak3, tumor necrosis factor receptors (Tnfr)p55/p75,
      interleukin 6 (IL-6) or interferon (IFN)-gamma alone was insufficient to
      alleviate LNP-siRNA-associated toxicities in mice. These indicate that activation
      of innate immune response is a primary trigger of systemic toxicities and that
      multiple innate immune pathways and cytokines can mediate toxic responses. Jak
      inhibitors are effective in mitigating LNP-siRNA-induced toxicities.

PMID- 21179009
TI  - MicroRNA-regulated, systemically delivered rAAV9: a step closer to CNS-restricted
      transgene expression.
AB  - Recombinant adeno-associated viruses (rAAVs) that can cross the blood-brain
      barrier and achieve efficient and stable transvascular gene transfer to the
      central nervous system (CNS) hold significant promise for treating CNS disorders.
      However, following intravascular delivery, these vectors also target liver,
      heart, skeletal muscle, and other tissues, which may cause untoward effects. To
      circumvent this, we used tissue-specific, endogenous microRNAs (miRNAs) to
      repress rAAV expression outside the CNS, by engineering perfectly complementary
      miRNA-binding sites into the rAAV9 genome. This approach allowed simultaneous
      multi-tissue regulation and CNS-directed stable transgene expression without
      detectably perturbing the endogenous miRNA pathway. Regulation of rAAV expression
      by miRNA was primarily via site-specific cleavage of the transgene mRNA,
      generating specific 5' and 3' mRNA fragments. Our findings promise to facilitate
      the development of miRNA-regulated rAAV for CNS-targeted gene delivery and other
      applications.

PMID- 21179010
TI  - Replication-competent lentivirus analysis of clinical grade vector products.
AB  - Lentiviral vectors are now in clinical trials for a variety of inherited and
      acquired disorders. A challenge for moving any viral vector into the clinic is
      the ability to screen the vector product for the presence of replication
      competent virus. Assay development for replication-competent lentivirus (RCL) is
      particularly challenging because recombination of vector packaging plasmids and
      cellular DNA leading to RCL has not been reported with the current viral vector
      systems. Therefore, the genomic structure of a RCL remains theoretical. In this
      report, we describe a highly sensitive RCL assay suitable for screening vector
      product and have screened large-scale vector supernatant, cells used in vector
      production, and cells transduced with clinical grade vector. We discuss the
      limitations and challenges of the current assay, and suggest modifications that
      may improve the suitability of this assay for screening US Food and Drug
      Administration (US FDA)-licensed products.

PMID- 21179011
TI  - Expressed cell-penetrating peptides can induce a bystander effect, but passage
      through the secretory pathway reduces protein transduction activity.
AB  - Despite advances in vector technology, inefficient gene transfer still limits
      clinical efficacy of cancer gene therapy. Cell-penetrating peptides (CPPs), such
      as the basic domain of the transactivator of transcription (Tat) protein of HIV
      1, are internalized by intact cells and have been used to deliver purified
      recombinant proteins. A combination of gene therapy with protein transduction
      technology could induce a strong bystander effect and represent a platform to
      deliver proteins to target cells. However, whether expressed CPP can facilitate
      intercellular trafficking, i.e., a bystander effect, is controversial. Our data
      suggest that expressed fusion proteins that contain the basic domain of Tat do
      not induce a detectable bystander effect. However, Tat-fusion proteins that also
      contain a secretory signal peptide (SP) can induce a bystander effect in vitro,
      although the in vivo effect is small. Surprisingly, despite the presence of a SP,
      the bystander effect does not seem to be related to secretion of the fusion
      protein. In fact, Tat-fusion proteins are secreted very inefficiently, and
      protein transduction seems largely mediated by fusion proteins that are released
      by cell lysis. Modification of Tat can improve secretion efficacy and prevent
      cleavage by the endoprotease furin, but passage through the secretory pathway is
      associated with reduced transduction activity of Tat-fusion proteins.

PMID- 21179012
TI  - Refractory heartburn: comparison of intercellular space diameter in documented
      GERD vs. functional heartburn.
AB  - OBJECTIVES: Refractory heartburn despite acid suppression may be explained by
      ongoing gastroesophageal reflux disease (GERD) or functional heartburn (FH),
      i.e., symptoms without evidence of GERD. Impedance-pH monitoring (impedance-pH)
      detects acid and nonacid reflux and is useful for evaluating acid-suppressed,
      refractory patients. Intercellular space diameter (ISD) of esophageal epithelium
      measured by transmission electron microscopy (TEM) is a marker of epithelial
      damage present in both erosive and nonerosive reflux disease. ISD has not been
      used to study refractory heartburn or FH. Our aim was to compare ISD in healthy
      controls and refractory heartburn patients with GERD and FH. METHODS: In
      refractory heartburn patients (heartburn more than twice/week for at least 2
      months despite proton pump inhibitor (PPI) b.i.d.), erosive esophagitis and/or
      abnormal impedance-pH (increased acid exposure or positive symptom index) defined
      GERD; normal esophagogastroduodenoscopy (EGD)/impedance-pH defined FH.
      Asymptomatic, healthy controls had normal EGD and pH-metry. Mean ISD in each
      subject, determined by blinded TEM of esophageal biopsies, was the average of 100
      measurements (10 measurements in each of 10 micrographs). RESULTS: In all, 11
      healthy controls, 11 FH, and 15 GERD patients were studied. Mean ISD was
      significantly higher in GERD compared with controls (0.87 vs. 0.32 MUm, P=0.003)
      and FH (0.87 vs. 0.42 MUm, P=0.012). Mean ISD was similar in FH and controls
      (0.42 vs. 0.32 MUm, P=0.1). The proportion of patients with abnormal ISD was
      significantly higher for GERD compared with FH (60 vs. 9%, P=0.014). CONCLUSIONS:
      ISD is increased in refractory heartburn patients with GERD but not those with
      FH. Our findings suggest that measurement of ISD by TEM might be a useful tool to
      distinguish GERD from FH in patients with refractory heartburn.

PMID- 21179013
TI  - Hepatic and extrahepatic cancer in cirrhosis: a longitudinal cohort study.
AB  - OBJECTIVES: We conducted a retrospective cohort study in cirrhotic patients to
      understand (i) the risk of developing hepatocellular carcinoma (HCC) after an
      initial negative screening computed tomography (CT) scan and its relationship
      with underlying etiology and (ii) the risk of extrahepatic cancers (EHCs).
      METHODS: Our cohort consisted of 952 cirrhotics who had at least one contrast
      enhanced CT scan over a 5-year period from 1997 to 2002. We assessed their risk
      of HCC and EHC until the study closure (31 December 2007). Using data from the
      Indiana State Cancer Registry (ISCR), standardized incidence ratios (SIRs) were
      calculated for HCC and EHC. RESULTS: The cohort's follow-up was 4.7+/-3.0 years.
      The frequency of HCC at baseline and during follow-up was 6.9 and 7.2%,
      respectively. The 1-, 3-, and 5-year HCC incidence after an initial negative CT
      scan was 1.2, 4.4, and 7.8%, respectively. The 1-, 3-, and 5-year EHC incidence
      was 2.2, 4.5, and 6.8%, respectively. The most common EHCs were breast, lung, and
      lymphoma. Incidence of both HCC (P=0.016) and EHC (P=0.004) varied significantly
      by the etiology of underlying cirrhosis. The SIRs for HCC and EHC were 186 (95%
      confidence interval (CI) 140-238) and 1.83 (95% CI 1.36-2.36), respectively.
      Compared with adjusted ISCR data, cirrhosis due to alcohol (SIR 2.73, 95% CI 1.14
      4.33) but not other etiologies had significantly higher incidence of EHC.
      CONCLUSIONS: This study furthers our understanding of HCC and EHC risk in
      cirrhosis. If confirmed by other studies, these data will assist in developing
      optimal strategies for monitoring of cancer in individuals with cirrhosis.

PMID- 21179014
TI  - Metabonomic, transcriptomic, and genomic variation of a population cohort.
AB  - Comprehensive characterization of human tissues promises novel insights into the
      biological architecture of human diseases and traits. We assessed metabonomic,
      transcriptomic, and genomic variation for a large population-based cohort from
      the capital region of Finland. Network analyses identified a set of highly
      correlated genes, the lipid-leukocyte (LL) module, as having a prominent role in
      over 80 serum metabolites (of 134 measures quantified), including lipoprotein
      subclasses, lipids, and amino acids. Concurrent association with immune response
      markers suggested the LL module as a possible link between inflammation,
      metabolism, and adiposity. Further, genomic variation was used to generate a
      directed network and infer LL module's largely reactive nature to metabolites.
      Finally, gene co-expression in circulating leukocytes was shown to be dependent
      on serum metabolite concentrations, providing evidence for the hypothesis that
      the coherence of molecular networks themselves is conditional on environmental
      factors. These findings show the importance and opportunity of systematic
      molecular investigation of human population samples. To facilitate and encourage
      this investigation, the metabonomic, transcriptomic, and genomic data used in
      this study have been made available as a resource for the research community.

PMID- 21179015
TI  - Nonsense-mediated decay targets have multiple sequence-related features that can
      inhibit translation.
AB  - Nonsense-mediated mRNA decay (NMD) is a surveillance system that eliminates
      transcripts with premature termination codons. In this study, we show that mRNAs
      targeted by NMD are also suppressed at the translational level. The low
      translational efficiency (TE) is a consequence of multiple features acting in
      concert, including low translation initiation rate, mediated by 5' secondary
      structure and by use of weak initiation sites, and low translation elongation
      speed, mediated by low codon usage bias. Despite low elongation rates, NMD
      transcripts show low ribosome density in the coding sequence, probably owing to
      low initiation rates, high abortion rates or rapid transit of the ribosome
      following initiation failure. The low TE is observed in the absence of NMD and is
      not explained by low transcript abundance. Translational inefficiency is
      flexible, such that NMD targets have increased TE upon starvation. We propose
      that the low TE predisposes to NMD and/or that it is part of a mechanism for
      regulation of NMD transcripts.

PMID- 21179016
TI  - A tunable dual-promoter integrator for targeting of cancer cells.
AB  - Precise discrimination between similar cellular states is essential for
      autonomous decision-making scenarios, such as in vivo targeting of diseased
      cells. Discrimination could be achieved by delivering an effector gene expressed
      under a highly active context-specific promoter. Yet, a single-promoter approach
      has linear response and offers limited control of specificity and efficacy. Here,
      we constructed a dual-promoter integrator, which expresses an effector gene only
      when the combined activity of two internal input promoters is high. A tunable
      response provides flexibility in choosing promoter inputs and effector gene
      output. Experiments using one premalignant and four cancer cell lines, over a
      wide range of promoter activities, revealed a digital-like response of input
      amplification following a sharp activation threshold. The response function is
      cell dependent with its overall magnitude increasing with degree of malignancy.
      The tunable digital-like response provides robustness, acts to remove input noise
      minimizing false-positive identification of cell states, and improves targeting
      precision and efficacy.

PMID- 21179017
TI  - Single-gene tuning of Caulobacter cell cycle period and noise, swarming motility,
      and surface adhesion.
AB  - Sensor histidine kinases underlie the regulation of a range of physiological
      processes in bacterial cells, from chemotaxis to cell division. In the gram
      negative bacterium Caulobacter crescentus, the membrane-bound histidine kinase,
      DivJ, is a polar-localized regulator of cell cycle progression and development.
      We show that DivJ localizes to the cell pole through a dynamic diffusion and
      capture mechanism rather than by active localization. Analysis of single C.
      crescentus cells in microfluidic culture demonstrates that controlled expression
      of divJ permits facile tuning of both the mean and noise of the cell division
      period. Simulations of the cell cycle that use a simplified protein interaction
      network capture previously measured oscillatory protein profiles, and
      recapitulate the experimental observation that deletion of divJ increases the
      cell cycle period and noise. We further demonstrate that surface adhesion and
      swarming motility of C. crescentus in semi-solid media can also be tuned by divJ
      expression. We propose a model in which pleiotropic control of polar cell
      development by the DivJ-DivK-PleC signaling pathway underlies divJ-dependent
      tuning of cell swarming and adhesion behaviors.

PMID- 21179018
TI  - Design principles of nuclear receptor signaling: how complex networking improves
      signal transduction.
AB  - The topology of nuclear receptor (NR) signaling is captured in a systems
      biological graphical notation. This enables us to identify a number of 'design'
      aspects of the topology of these networks that might appear unnecessarily complex
      or even functionally paradoxical. In realistic kinetic models of increasing
      complexity, calculations show how these features correspond to potentially
      important design principles, e.g.: (i) cytosolic 'nuclear' receptor may shuttle
      signal molecules to the nucleus, (ii) the active export of NRs may ensure that
      there is sufficient receptor protein to capture ligand at the cytoplasmic
      membrane, (iii) a three conveyor belts design dissipating GTP-free energy,
      greatly aids response, (iv) the active export of importins may prevent
      sequestration of NRs by importins in the nucleus and (v) the unspecific nature of
      the nuclear pore may ensure signal-flux robustness. In addition, the models
      developed are suitable for implementation in specific cases of NR-mediated
      signaling, to predict individual receptor functions and differential sensitivity
      toward physiological and pharmacological ligands.

PMID- 21179019
TI  - Emergence of tissue polarization from synergy of intracellular and extracellular
      auxin signaling.
AB  - Plant development is exceptionally flexible as manifested by its potential for
      organogenesis and regeneration, which are processes involving rearrangements of
      tissue polarities. Fundamental questions concern how individual cells can
      polarize in a coordinated manner to integrate into the multicellular context. In
      canalization models, the signaling molecule auxin acts as a polarizing cue, and
      feedback on the intercellular auxin flow is key for synchronized polarity
      rearrangements. We provide a novel mechanistic framework for canalization, based
      on up-to-date experimental data and minimal, biologically plausible assumptions.
      Our model combines the intracellular auxin signaling for expression of PINFORMED
      (PIN) auxin transporters and the theoretical postulation of extracellular auxin
      signaling for modulation of PIN subcellular dynamics. Computer simulations
      faithfully and robustly recapitulated the experimentally observed patterns of
      tissue polarity and asymmetric auxin distribution during formation and
      regeneration of vascular systems and during the competitive regulation of shoot
      branching by apical dominance. Additionally, our model generated new predictions
      that could be experimentally validated, highlighting a mechanistically
      conceivable explanation for the PIN polarization and canalization of the auxin
      flow in plants.

PMID- 21179020
TI  - Defining the budding yeast chromatin-associated interactome.
AB  - We previously reported a novel affinity purification (AP) method termed modified
      chromatin immunopurification (mChIP), which permits selective enrichment of DNA
      bound proteins along with their associated protein network. In this study, we
      report a large-scale study of the protein network of 102 chromatin-related
      proteins from budding yeast that were analyzed by mChIP coupled to mass
      spectrometry. This effort resulted in the detection of 2966 high confidence
      protein associations with 724 distinct preys. mChIP resulted in significantly
      improved interaction coverage as compared with classical AP methodology for ~75%
      of the baits tested. Furthermore, mChIP successfully identified novel binding
      partners for many lower abundance transcription factors that previously failed
      using conventional AP methodologies. mChIP was also used to perform targeted
      studies, particularly of Asf1 and its associated proteins, to allow for a
      understanding of the physical interplay between Asf1 and two other histone
      chaperones, Rtt106 and the HIR complex, to be gained.

PMID- 21179021
TI  - Evolution, genomic analysis, and reconstruction of isobutanol tolerance in
      Escherichia coli.
AB  - Escherichia coli has been engineered to produce isobutanol, with titers reaching
      greater than the toxicity level. However, the specific effects of isobutanol on
      the cell have never been fully understood. Here, we aim to identify genotype
      phenotype relationships in isobutanol response. An isobutanol-tolerant mutant was
      isolated with serial transfers. Using whole-genome sequencing followed by gene
      repair and knockout, we identified five mutations (acrA, gatY, tnaA, yhbJ, and
      marCRAB) that were primarily responsible for the increased isobutanol tolerance.
      We successfully reconstructed the tolerance phenotype by combining deletions of
      these five loci, and identified glucosamine-6-phosphate as an important
      metabolite for isobutanol tolerance, which presumably enhanced membrane
      synthesis. The isobutanol-tolerant mutants also show increased tolerance to n
      butanol and 2-methyl-1-butanol, but showed no improvement in ethanol tolerance
      and higher sensitivity to hexane and chloramphenicol than the parental strain.
      These results suggest that C4, C5 alcohol stress impacts the cell differently
      compared with the general solvent or antibiotic stresses. Interestingly, improved
      isobutanol tolerance did not increase the final titer of isobutanol production.

PMID- 21179022
TI  - Defining the transcriptome and proteome in three functionally different human
      cell lines.
AB  - An essential question in human biology is how cells and tissues differ in gene
      and protein expression and how these differences delineate specific biological
      function. Here, we have performed a global analysis of both mRNA and protein
      levels based on sequence-based transcriptome analysis (RNA-seq), SILAC-based mass
      spectrometry analysis and antibody-based confocal microscopy. The study was
      performed in three functionally different human cell lines and based on the
      global analysis, we estimated the fractions of mRNA and protein that are cell
      specific or expressed at similar/different levels in the cell lines. A highly
      ubiquitous RNA expression was found with >60% of the gene products detected in
      all cells. The changes of mRNA and protein levels in the cell lines using SILAC
      and RNA ratios show high correlations, even though the genome-wide dynamic range
      is substantially higher for the proteins as compared with the transcripts. Large
      general differences in abundance for proteins from various functional classes are
      observed and, in general, the cell-type specific proteins are low abundant and
      highly enriched for cell-surface proteins. Thus, this study shows a path to
      characterize the transcriptome and proteome in human cells from different
      origins.

PMID- 21179023
TI  - Cross-species chemogenomic profiling reveals evolutionarily conserved drug mode
      of action.
AB  - We present a cross-species chemogenomic screening platform using libraries of
      haploid deletion mutants from two yeast species, Saccharomyces cerevisiae and
      Schizosaccharomyces pombe. We screened a set of compounds of known and unknown
      mode of action (MoA) and derived quantitative drug scores (or D-scores),
      identifying mutants that are either sensitive or resistant to particular
      compounds. We found that compound-functional module relationships are more
      conserved than individual compound-gene interactions between these two species.
      Furthermore, we observed that combining data from both species allows for more
      accurate prediction of MoA. Finally, using this platform, we identified a novel
      small molecule that acts as a DNA damaging agent and demonstrate that its MoA is
      conserved in human cells.

PMID- 21179024
TI  - Evolving a robust signal transduction pathway from weak cross-talk.
AB  - We have evolved a robust two-component signal transduction pathway from a sensor
      kinase (SK) and non-partner response regulator (RR) that show weak cross-talk in
      vitro and no detectable cross-talk in vivo in wild-type strains. The SK, CpxA, is
      bifunctional, with both kinase and phosphatase activities for its partner RR. We
      show that by combining a small number of mutations in CpxA that individually
      increase phosphorylation of the non-partner RR OmpR, phosphatase activity against
      phospho-OmpR emerges. The resulting circuit also becomes responsive to input
      signal to CpxA. The effects of combining these mutations in CpxA appear to
      reflect complex intragenic interactions between multiple sites in the protein.
      However, by analyzing a simple model of two-component signaling, we show that the
      behavior can be explained by a monotonic change in a single parameter controlling
      protein-protein interaction strength. The results suggest one possible mode of
      evolution for two-component systems with bifunctional SKs whereby the remarkable
      properties and competing reactions that characterize these systems can emerge by
      combining mutations of the same effect.

PMID- 21179027
TI  - Integrative model of genomic factors for determining binding site selection by
      estrogen receptor-alpha.
AB  - A major question in transcription factor (TF) biology is why a TF binds to only a
      small fraction of motif eligible binding sites in the genome. Using the estrogen
      receptor-alpha as a model system, we sought to explicitly define parameters that
      determine TF-binding site selection. By examining 12 genetic and epigenetic
      parameters, we find that an energetically favorable estrogen response element
      (ERE) motif sequence, co-occupancy by the TF FOXA1, the presence of the H3K4me1
      mark and an open chromatin configuration in the pre-ligand state provide
      specificity for ER binding. These factors can model estrogen-induced ER binding
      with high accuracy (ROC-AUC=0.95 and 0.88 using different genomic backgrounds).
      Moreover, when assessed in another estrogen-responsive cell line, this model was
      highly predictive for ERalpha binding (ROC-AUC=0.86). Variance in binding site
      selection between MCF-7 and T47D resides in sites with suboptimal ERE motifs, but
      modulated by the chromatin configuration. These results suggest a definable
      interplay between sequence motifs and local chromatin in selecting TF binding.

PMID- 21179025
TI  - A comprehensive map of the mTOR signaling network.
AB  - The mammalian target of rapamycin (mTOR) is a central regulator of cell growth
      and proliferation. mTOR signaling is frequently dysregulated in oncogenic cells,
      and thus an attractive target for anticancer therapy. Using CellDesigner, a
      modeling support software for graphical notation, we present herein a
      comprehensive map of the mTOR signaling network, which includes 964 species
      connected by 777 reactions. The map complies with both the systems biology markup
      language (SBML) and graphical notation (SBGN) for computational analysis and
      graphical representation, respectively. As captured in the mTOR map, we review
      and discuss our current understanding of the mTOR signaling network and highlight
      the impact of mTOR feedback and crosstalk regulations on drug-based cancer
      therapy. This map is available on the Payao platform, a Web 2.0 based community
      wide interactive process for creating more accurate and information-rich
      databases. Thus, this comprehensive map of the mTOR network will serve as a tool
      to facilitate systems-level study of up-to-date mTOR network components and
      signaling events toward the discovery of novel regulatory processes and
      therapeutic strategies for cancer.

PMID- 21179028
TI  - Replication study of SNP associations for colorectal cancer in Hong Kong Chinese.
AB  - BACKGROUND: Recent genome-wide association studies of colorectal cancer (CRC)
      have identified common single-nucleotide polymorphisms (SNPs) mapping to 10
      independent loci that confer modest increased risk. These studies have been
      conducted in European populations and it is unclear whether these observations
      generalise to populations with different ethnicities and rates of CRC. METHODS:
      An association study was performed on 892 CRC cases and 890 controls recruited
      from the Hong Kong Chinese population, genotyping 32 SNPs, which were either
      associated with CRC in previous studies or are in close proximity to previously
      reported risk SNPs. RESULTS: Twelve of the SNPs showed evidence of an
      association. The strongest associations were provided by rs10795668 on 10p14,
      rs4779584 on 15q14 and rs12953717 on 18q21.2. There was significant linear
      association between CRC risk and the number of independent risk variants
      possessed by an individual (P=2.29 * 10(-5)). CONCLUSION: These results indicate
      that some previously reported SNP associations also impact on CRC risk in the
      Chinese population. Possible reasons for failure of replication for some loci
      include inadequate study power, differences in allele frequency, linkage
      disequilibrium structure or effect size between populations. Our results suggest
      that many associations for CRC are likely to generalise across populations.

PMID- 21179029
TI  - Attenuated reovirus displays oncolysis with reduced host toxicity.
AB  - BACKGROUND: Although the naturally occurring reovirus causes only mild symptoms
      in humans, it shows considerable potential as an oncolytic agent because of its
      innate ability to target cancer cells. In immunocompromised hosts, however, wild
      type reovirus can target healthy tissues, including heart, liver, pancreas and
      neural structures. METHODS: We characterized an attenuated form of reovirus (AV)
      derived from a persistently infected cell line through sequence analysis, as well
      as western blot and in vitro transcription and translation techniques. To examine
      its pathogenesis and oncolytic potential, AV reovirus was tested on healthy
      embryonic stem cells, various non-transformed and transformed cell lines, and in
      severe combined immunodeficiency (SCID) mice with tumour xenografts. RESULTS:
      Sequence analysis of AV reovirus revealed a premature STOP codon in its sigma 1
      attachment protein. Western blot and in vitro translation confirmed the presence
      of a truncated sigma1. In comparison to wild-type reovirus, AV reovirus did not
      kill healthy stem cells or induce black tail formation in SCID mice. However, it
      did retain its ability to target cancer cells and reduce tumour size. CONCLUSION:
      Despite containing a truncated attachment protein, AV reovirus still
      preferentially targets cancer cells, and compared with wild-type reovirus it
      shows reduced toxicity when administered to immunodeficient hosts, suggesting the
      potential use of AV reovirus in combination cancer therapy.

PMID- 21179030
TI  - CXCL9 induces chemotaxis, chemorepulsion and endothelial barrier disruption
      through CXCR3-mediated activation of melanoma cells.
AB  - BACKGROUND: Metastasis is associated with poor prognosis for melanoma. The
      formation of metastases is a multi-step process, in which cancer cells can
      subsequently acquire the potential to intravasate into the blood or lymph
      vessels, disseminate through the circulation, extravasate through the endothelium
      and invade the connective tissue. There is increasing evidence that chemokines
      have a pivotal role in the dissemination and establishment of melanoma
      metastasis. METHODS: We isolated melanoma cells from melanoma metastasis and
      performed different migration assays and transendothelial resistance measurements
      of endothelial monolayers co-cultured with melanoma cells, in order to monitor
      barrier function and diapedesis and confirmed these results by confocal
      microscopy. RESULTS: We observed that tumour endothelial cells (ECs) secrete high
      levels of CXCL9 in all, and CXCL10 in most melanoma metastases. Migration studies
      revealed that low concentrations of these chemokines induce chemotaxis, whereas
      high concentrations induce spontaneous migration of melanoma cells
      (chemokinesis/chemorepulsion) and the disruption of the endothelial barrier,
      resulting in an accelerated transendothelial migration (TEM). Addition of anti
      CXCL9 or anti-CXCR3 antibodies to the co-cultures delayed the TEM of melanoma
      cells. CONCLUSION: Our data represent novel mechanisms by which tumour cells in
      melanoma metastases might use the chemokine-expressing endothelium to leave the
      tumour and eventually to form additional metastases at distinct sites.

PMID- 21179031
TI  - Single agent and combination studies of pralatrexate and molecular correlates of
      sensitivity.
AB  - BACKGROUND: Pralatrexate is a dihydrofolate reductase (DHFR) inhibitor with high
      affinity for reduced folate carrier 1 (RFC-1) and folylpolyglutamate synthetase
      (FPGS), resulting in extensive internalization and accumulation in tumour cells.
      Pralatrexate is approved in the US for the treatment of relapsed or refractory
      peripheral T-cell lymphoma and is being investigated in various malignancies.
      Here, we evaluated molecular correlates of sensitivity to pralatrexate and
      explored combinations with a variety of anticancer agents. METHODS:
      Antiproliferative effects of pralatrexate were evaluated in 15 human-cancer cell
      lines using the MTT assay. Gene expression was evaluated using qRT-PCR. RESULTS:
      Pralatrexate and methotrexate had a similar pattern of cytotoxicity, pralatrexate
      being more potent. Pralatrexate potentiated the effects of platinum drugs,
      antimetabolites and EGFR inhibitors. Dose- and time-dependent cytotoxicity of
      pralatrexate correlated with high mRNA expression of FPGS. Acquired resistance to
      pralatrexate was associated with decreased RFC-1 expression, whereas methotrexate
      resistance correlated with increased DHFR expression, suggesting different
      mechanisms of acquired resistance. CONCLUSION: Pralatrexate was more potent than
      methotrexate in a panel of solid tumour lines. Our findings support the further
      clinical development of pralatrexate in combination with certain cytotoxics and
      targeted therapies, and suggest that RFC-1, FPGS and DHFR may be potential
      biomarkers of outcome.

PMID- 21179032
TI  - Diabetogenic glucose and insulin concentrations modulate transcriptome and
      protein levels involved in tumour cell migration, adhesion and proliferation.
AB  - BACKGROUND: During the last decade, epidemiological studies uncovered the
      tremendous impact of metabolic syndrome/diabetes mellitus type 2 (DM T2) as risk
      factors of the progression of cancer. Therefore, we studied the impact of
      diabetogenic glucose and insulin concentrations on the activities of tumour
      cells, because little is known about how high glucose and insulin levels are
      influencing gene activities causing changes in the signal cascade activities with
      respect to kinases involved in the proliferation and migration of cancer cells.
      METHODS: To address this question we analysed the activity of more than 400 gene
      signatures related to (i) cell cycle, (ii) cell movement as well as (iii) signal
      transduction. We examined transcriptomes of kinases (PKCalpha, PI3K), cadherins
      (E-, N- VE-), integrins and cyclins by comparing physiological (5.5 mM) vs
      diabetogenic (11 mM) glucose concentrations (without and with insulin). RESULTS:
      Proliferation assays revealed that high levels of glucose (11 mM) and insulin
      (100 ng ml(-1)) did promote the proliferation of the tumour cell lines HT29,
      SW480, MCF-7, MDA MB468, PC3 and T24. Using a 3D-migration assay, we have shown
      that high glucose concentrations caused increased motility rates of the tumour
      cells. The increase in migratory activity at high glucose and insulin
      concentrations was mediated by an activation of PI3K, PKCalpha and MLCK, as
      figured out by the pharmacological inhibitors wortmannin, Go6976 and ML-7.
      CONCLUSION: We present molecular and functional data, which could help to
      understand how hyperglycaemia and hyperinsulinemia might trigger tumour cell
      proliferation and motility in patients, too.

PMID- 21179034
TI  - Identification of HLA-A2-restricted CTL epitopes of a novel tumour-associated
      antigen, KIF20A, overexpressed in pancreatic cancer.
AB  - BACKGROUND: Identification of tumour-associated antigens (TAAs) that induce
      cytotoxic T lymphocytes (CTLs) specific to cancer cells is critical for the
      development of anticancer immunotherapy. In this study, we aimed at identifying a
      novel TAA of pancreatic cancer for immunotherapy. METHODS: On the basis of the
      genome-wide cDNA microarray analysis, we focused on KIF20A (also known as
      RAB6KIFL/MKlp2) as a candidate TAA in pancreatic cancer cells. The HLA-A2
      (A*02:01)-restricted CTL epitopes of KIF20A were identified using HLA-A2
      transgenic mice (Tgm) and the peptides were examined to check whether they could
      generate human CTLs exhibiting cytotoxic responses against KIF20A(+), HLA-A2(+)
      tumour cells in vitro. RESULTS: KIF20A was overexpressed in pancreatic cancer and
      in some other malignancies, but not in their non-cancerous counterparts and many
      normal adult tissues. We found that KIF20A-2 (p12-20, LLSDDDVVV), KIF20A-8 (p809
      817, CIAEQYHTV), and KIF20A-28 (p284-293, AQPDTAPLPV) peptides could induce HLA
      A2-restricted CTLs in HLA-A2 Tgm without causing autoimmunity. Peptide-reactive
      human CTLs were generated from peripheral blood mononuclear cells of HLA-A2(+)
      healthy donors by in vitro stimulation with the three peptides, and those CTLs
      successfully exhibited cytotoxic responses to cancer cells expressing both KIF20A
      and HLA-A2. CONCLUSION: KIF20A is a novel promising candidate for anticancer
      immunotherapeutic target for pancreatic cancers.

PMID- 21179035
TI  - Toll-like receptor 2 is present in the microenvironment of oral squamous cell
      carcinoma.
AB  - BACKGROUND: The aim of this study was to investigate the expression of toll-like
      receptor 2 (TLR2) on cells associated with oral squamous cell carcinoma,
      epithelial dysplasia and irritative hyperplasia, using immunohistochemistry.
      RESULTS: More immune cells expressed TLR2 in carcinoma and dysplasia than in
      hyperplasia (P<0.001). No hyperplastic samples showed positive TLR2 staining on
      keratinocytes, whereas keratinocytes in 64% of cases of carcinoma and 74% of
      cases of dysplasia were TLR2 positive. CONCLUSION: Positive TLR2 expression in
      the microenvironment suggests activation of immune surveillance against the
      altered epithelium, whereas TLR2 expression by malignant keratinocytes may be
      indicative of resistance to apoptosis as a pro-survival mechanism.

PMID- 21179033
TI  - Long-term psychosocial impact of alternative management policies in women with
      low-grade abnormal cervical cytology referred for colposcopy: a randomised
      controlled trial.
AB  - BACKGROUND: The debate continues regarding the best management for women with low
      grade abnormal cervical cytology attending colposcopy. We compared psychosocial
      outcomes of alternative management policies in these women. METHODS: In all, 989
      women, aged 20-59 years, with low-grade abnormal cytology, were randomised to
      immediate large loop excision (LLETZ) or two to four targeted punch biopsies
      taken immediately with recall for LLETZ if these showed cervical intra-epithelial
      neoplasia 2/3. At 6 weeks after the last procedure, women completed the hospital
      anxiety and depression scale (HADS) and the impact of event scale (IES). At 12,
      18, 24 and 30 months post recruitment, women completed the HADS and process
      outcome specific measure (POSM). Prevalence of significant depression (>= 8),
      significant anxiety (>= 11) and distress (>= 9) and median POSM scores were
      compared between arms. Multivariate odds ratios (ORs) for immediate LLETZ vs
      biopsy and recall were computed. RESULTS: Over the entire follow-up, there was no
      significant difference between arms in cumulative prevalence or risk of
      significant depression (OR=0.78, 95% CI 0.52-1.17) or significant anxiety
      (OR=0.83, 95% CI 0.57-1.19). At 6 weeks post procedure, distress did not differ
      significantly between arms. At later time points, 8-11% had significant
      depression and 14-16% had significant anxiety but with no differences between
      arms. The POSM scores did not differ between the arms. CONCLUSIONS: There is no
      difference in long- or short-term psychosocial outcomes of immediate LLETZ and
      punch biopsies with selective recall.

PMID- 21179036
TI  - A prospective study of chemotherapy-induced febrile neutropenia in the South West
      London Cancer Network. Interpretation of study results in light of NCAG/NCEPOD
      findings.
AB  - BACKGROUND: Chemotherapy-induced febrile neutropenia is a medical emergency
      complicating the treatment of many cancer patients. It is associated with
      considerable morbidity and mortality, as well as impacting on healthcare
      resources. METHODS: A prospective study of all cases of chemotherapy-induced
      febrile neutropenia in the South West London Cancer Network was conducted over a
      4-month period. Factors including demographics, treatment history, management of
      febrile neutropenia and outcome were recorded. RESULTS AND CONCLUSION: Our
      results reflect those of the recent National Chemotherapy Advisory Group (NCEPOD,
      2008)/National Confidential Enquiry into Patient Outcomes and Death reports
      (NCAG, 2009) and highlight the need for network-wide clinical care pathways to
      improve outcomes in this area.

PMID- 21179037
TI  - PBOX-15, a novel microtubule targeting agent, induces apoptosis, upregulates
      death receptors, and potentiates TRAIL-mediated apoptosis in multiple myeloma
      cells.
AB  - BACKGROUND: In recent years, much progress has been made in the treatment of
      multiple myeloma. However, a major limitation of existing chemotherapeutic drugs
      is the eventual emergence of resistance; hence, the development of novel agents
      with new mechanisms of action is pertinent. Here, we describe the activity and
      mechanism of action of pyrrolo-1,5-benzoxazepine-15 (PBOX-15), a novel
      microtubule-targeting agent, in multiple myeloma cells. METHODS: The anti-myeloma
      activity of PBOX-15 was assessed using NCI-H929, KMS11, RPMI8226, and U266 cell
      lines, and primary myeloma cells. Cell cycle distribution, apoptosis, cytochrome
      c release, and mitochondrial inner membrane depolarisation were analysed by flow
      cytometry; gene expression analysis was carried out using TaqMan Low Density
      Arrays; and expression of caspase-8 and Bcl-2 family of proteins was assessed by
      western blot analysis. RESULTS: Pyrrolo-1,5-benzoxazepine-15 induced apoptosis in
      ex vivo myeloma cells and in myeloma cell lines. Death receptor genes were
      upregulated in both NCI-H929 and U266 cell lines, which displayed the highest and
      lowest apoptotic responses, respectively, following treatment with PBOX-15. The
      largest increase was detected for the death receptor 5 (DR5) gene, and
      cotreatment of both cell lines with tumour necrosis factor-related apoptosis
      inducing ligand (TRAIL), the DR5 ligand, potentiated the apoptotic response. In
      NCI-H929 cells, PBOX-15-induced apoptosis was shown to be caspase-8 dependent,
      with independent activation of extrinsic and intrinsic apoptotic pathways. A
      caspase-8-dependent decrease in expression of Bim(EL) preceded downregulation of
      other Bcl-2 proteins (Bid, Bcl-2, Mcl-1) in PBOX-15-treated NCI-H929 cells.
      CONCLUSION: PBOX-15 induces apoptosis and potentiates TRAIL-induced cell death in
      multiple myeloma cells. Thus, PBOX-15 represents a promising agent, with a
      distinct mechanism of action, for the treatment of this malignancy.

PMID- 21179038
TI  - The effect of self-sampled HPV testing on participation to cervical cancer
      screening in Italy: a randomised controlled trial (ISRCTN96071600).
AB  - BACKGROUND: In Italy, cervical cancer screening programmes actively invite women
      aged 25-64 years. Programmes are hindered by low participation. METHODS: A sample
      of non-responder women aged 35-64 years, belonging to three different programmes
      (in Rome, Florence and Teramo), was randomly split into four arms: two control
      groups received standard recall letters to perform either Pap-test (first group)
      or human papillomavirus (HPV) test (second group) at the clinic. A third arm was
      sent letters offering a self-sampler for HPV testing, to be requested by phone,
      whereas a fourth group was directly sent the self-samplers home. RESULTS:
      Compliance with standard recall was 13.9% (N619). Offering HPV test at the clinic
      had a nonsignificant effect on compliance (N616, relative risk (RR)=1.08; 95%
      CI=0.82-1.41). Self-sampler at request had the poorest performance, 8.7% (N622,
      RR=0.62; 95% CI=0.45-0.86), whereas direct mailing of the self-sampler registered
      the highest compliance: 19.6% (N616, RR=1.41; 95% CI=1.10-1.82). This effect on
      compliance was observed only in urban areas, Florence and Rome (N438, RR=1.69;
      95% CI=1.24-2.30), but not in Abruzzo (N178, RR=0.95; 95% CI=0.61-1.50), a
      prevalently rural area. CONCLUSIONS: Mailing self-samplers to non-responders may
      increase compliance as compared with delivering standard recall letters.
      Nevertheless, effectiveness is context specific and the strategy costs should be
      carefully considered.

PMID- 21179045
TI  - Phenalinolactones A-D, terpenoglycoside antibiotics from Streptomyces sp. Tu
      6071.
AB  - Four new terpenoglycoside antibiotics, phenalinolactones A-D were isolated from
      Streptomyces sp. Tu 6071. The structures were elucidated on the basis of detailed
      NMR and MS analyses. Phenalinolactones combine a diterpenoid tricycle, a 2,3,6
      trideoxysugar, a pyrrole-carboxylic acid and an uncommonly oxidized unsaturated
      gamma-lactone in a unique manner. Phenalinolactones show an inhibitory activity
      against gram-positive bacteria.

PMID- 21179039
TI  - Epstein-Barr virus as a marker of biological aggressiveness in breast cancer.
AB  - PURPOSE: Although a potential role of the Epstein-Barr virus (EBV) in the
      pathogenesis of breast cancer (BC) has been underlined, results remain
      conflicting. Particularly, the impact of EBV infection on biological markers of
      BC has received little investigation. METHODS: In this study, we established the
      frequency of EBV-infected BC using real-time quantitative PCR (RT-PCR) in 196 BC
      specimens. Biological and pathological characteristics according to EBV status
      were evaluated. RESULTS: EBV DNA was present in 65 of the 196 (33.2%) cases
      studied. EBV-positive BCs tended to be tumours with a more aggressive phenotype,
      more frequently oestrogen receptor negative (P=0.05) and with high histological
      grade (P=0.01). Overexpression of thymidine kinase activity was higher in EBV
      infected BC (P=0.007). The presence of EBV was weakly associated with HER2 gene
      amplification (P=0.08). CONCLUSION: Our study provides evidence for EBV
      associated BC undergoing distinct carcinogenic processes, with more aggressive
      features.

PMID- 21179046
TI  - Xylaropyrone, a new gamma-pyrone from the endophytic fungus Xylaria feejeensis
      MU18.

PMID- 21179047
TI  - A novel class of geldanamycin derivatives as HCV replication inhibitors targeting
      on Hsp90: synthesis, structure-activity relationships and anti-HCV activity in
      GS4.3 replicon cells.
AB  - A novel class of geldanamycin (GA) derivatives as hepatitis C virus (HCV)
      replication inhibitors has been synthesized and their anti-HCV activities were
      evaluated in GS4.3 HCV replicon cells. Most of the synthesized compounds
      demonstrated potential activities against HCV in vitro. Substitution with an
      aliphatic cyclic group (2b) and polar phosphate group (2f) at the 17 position of
      GA resulted in more potent inhibitory activity. The configurations of the
      tetrahydrofurfurylamino (THFM) substituents obviously affected their antiviral
      activities. The 2b with a 2'-(R)-THFM group at the 17 position showed much potent
      activity and higher selectivity than its 2'-(S) and 2'-(R, S) epimers. In the
      tested GA derivatives, 2b and 2f show the most potential leading compounds for
      development of novel anti-HCV agents.

PMID- 21179048
TI  - Association of maternal folate nutrition and serum C-reactive protein
      concentrations with gestational age at delivery.
AB  - BACKGROUND/OBJECTIVES: C-reactive protein (CRP) is the most extensively studied
      inflammatory risk marker, and elevated serum CRP concentrations in pregnant women
      are known to be associated with subsequent development of preeclampsia and
      preterm delivery. Researchers have suggested that folate intake may help to
      control the inflammation process. We examined whether folate nutrition modifies
      the relationship between serum CRP concentration and gestational age at delivery.
      SUBJECTS/METHODS: Serum CRP concentrations were analyzed in 815 pregnant women
      between 12 and 28 weeks of gestation. Dietary intakes were assessed using a 24-h
      dietary recall. The serum folate and high-sensitivity CRP concentrations were
      analyzed by radioassay and latex agglutination tests, respectively. RESULTS:
      Serum CRP concentration was negatively correlated (P < 0.001) with gestational
      age at delivery. Serum folate concentration was negatively correlated (P < 0.01)
      with serum CRP concentration, and total dietary folate intake was positively
      correlated (P < 0.001) with serum folate concentration. Multiple regression
      analysis after adjustment for covariates revealed that maternal CRP
      concentrations were negatively associated with gestational age at delivery; these
      negative associations existed only when folate intake during pregnancy was below
      the Korean estimated average requirements (520 MUg dietary folate equivalent per
      day), and serum folate concentrations were above the normal (6 ng/ml).
      CONCLUSIONS: We found that adequate maternal folate intake during pregnancy may
      have a beneficial role against shorter gestational age at delivery, which is
      associated with higher serum CRP concentrations in pregnant women.

PMID- 21179049
TI  - Dietary patterns, bone resorption and bone mineral density in early post
      menopausal Scottish women.
AB  - BACKGROUND/OBJECTIVES: Several nutrients affect bone turnover. Dietary patterns
      may provide insights into which foods are important and how nutrition affects
      bone health. The aim of this study was to investigate the associations between
      dietary patterns, bone turnover and bone mineral density (BMD). SUBJECTS/METHODS:
      This cross-sectional study examined 3236 Scottish women age 50-59 years, who were
      members of the Aberdeen Prospective Osteoporosis Screening Study. They had hip
      and spine BMD measurements (dual-energy X-ray absorptiometry) and provided
      samples for bone turnover markers. Diet was assessed by a validated food
      frequency questionnaire encompassing 98 foods, from which 35 food groups were
      systematically created. Dietary patterns were defined by principal components
      analysis. The bone measures were regressed onto the dietary pattern and adjusted
      for potential confounders. RESULTS: Five dietary patterns were identified, three
      of which were associated with bone health. The 'healthy' pattern was associated
      with decreased bone resorption (r = 0.081, P < 0.001). Two other patterns
      (processed foods and snack food) were associated with lower BMD (femoral neck r =
      -0.056, r = -0.044, P < 0.001, respectively). CONCLUSIONS: Dietary pattern may
      influence bone turnover and BMD. A healthy dietary pattern with high intakes of
      fruit and vegetables may lead to less bone resorption, and a poor dietary pattern
      rich in processed foods is associated with a decrease in BMD. This study confirms
      that a healthy diet is required for strong bones, and highlights that a nutrient
      poor diet is a risk factor for osteoporosis.

PMID- 21179050
TI  - Effects of body size and sociodemographic characteristics on differences between
      self-reported and measured anthropometric data in middle-aged men and women: the
      EPIC-Norfolk study.
AB  - BACKGROUND/OBJECTIVES: To investigate the effects of body size and
      sociodemographic characteristics on differences between self-reported (SR) and
      measured anthropometric data in men and women. SUBJECTS/METHODS: This study
      comprises 9933 men and 11,856 women aged 39-79 years at baseline survey (1993
      1997) in the EPIC-Norfolk study (Norfolk arm of the European Investigation into
      Cancer and Nutrition Study). The effects of sex, measured height, weight, age
      group, educational level and social class on differences between SR and measured
      weight, height, body mass index (BMI), waist, hip and waist-to-hip ratio (WHR)
      were examined. RESULTS: There were systematic differences between SR and measured
      anthropometric measurements by sex, measured height, weight and sociodemographic
      characteristics. Height was overestimated in both sexes while weight, waist, hip,
      and consequently, BMI and WHR were underestimated. Being male, shorter, heavier,
      older, and having no educational qualifications and manual occupation were
      independently associated with overreporting of height, and underreporting of
      weight was associated independently with being female, shorter, heavier, younger
      age, and higher education level and social class. Underreporting of waist
      circumference was strongly associated with being female and higher measured waist
      circumference, while underreporting of hip circumference was associated with
      being male and higher measured hip circumference. Furthermore, there was
      substantial degree of misclassification of BMI and waist circumference categories
      for both general and central obesity associated with SR data. CONCLUSIONS: These
      findings suggest that errors in SR anthropometric data, especially waist and hip
      circumference are influenced by actual body size as well as sociodemographic
      characteristics. These systematic differences may influence associations between
      SR anthropometric measures and health outcomes in epidemiological studies.

PMID- 21179051
TI  - Fine bakery wares with label claims in Europe and their categorisation by
      nutrient profiling models.
AB  - BACKGROUND/OBJECTIVES: This study assesses a range of commercially available fine
      bakery wares with nutrition or health related on-pack communication against the
      criteria of selected nutrient profiling models. Different purposes of the
      application of nutrient profiles were considered, including front-of-pack
      signposting and the regulation of claims or advertising. SUBJECTS/METHODS: More
      than 200 commercially available fine bakery wares carrying claims were identified
      in Germany, France, Spain, Sweden and United Kingdom and evaluated against five
      nutrient profiling models. All models were assessed regarding their underlying
      principles, generated results and inter-model agreement levels. RESULTS: Total
      energy, saturated fatty acids, sugars, sodium and fibre were critical parameters
      for the categorisation of products. The Choices Programme was the most
      restrictive model in this category, while the Food and Drug Administration model
      allowed the highest number of products to qualify. According to all models, more
      savoury than sweet products met the criteria. On average, qualifying products
      contained less than half the amounts of nutrients to limit and more than double
      the amount of fibre compared with all the products in the study. None of the
      models had a significant impact on the average energy contents. CONCLUSIONS:
      Nutrient profiles can be applied to identify fine bakery wares with a
      significantly better nutritional composition than the average range of products
      positioned as healthier. Important parameters to take into account include
      energy, saturated fatty acids, sugars, sodium and fibre. Different criteria sets
      for subcategories of fine bakery wares do not seem necessary.

PMID- 21179052
TI  - Vitamin D deficiency in Spain: a population-based cohort study.
AB  - BACKGROUND: Vitamin D deficiency is common worldwide. No homogenous reference
      values have yet been established and no studies of values have been conducted in
      Spain involving a large number of participants. OBJECTIVE: To study the
      population concentrations of vitamin D in a representative sample of the Spanish
      population. SUBJECTS/METHODS: The study involved two cohorts from Spain, the
      Asturias study and the Pizarra study, which are two prospective, population-based
      studies involving 2260 participants. In 1262 subjects (age: 20-83 years) we
      studied 25-hydroxyvitamin D, intact parathyroid hormone (iPTH), calcium,
      phosphorus and creatinine. RESULTS: The median population values of 25
      hydroxyvitamin D and iPTH were 22.46 ng/ml and 42.29 pg/ml, respectively. The
      values of 25-hydroxyvitamin D were significantly higher in summer and correlated
      with age (beta = -0.05 +/- 0.01, P < 0.0001), creatinine (beta = 6.42 +/- 1.17, P
      < 0.0001) and iPTH (-0.07 +/- 0.01, P < 0.0001), but not with calcium, phosphorus
      or sex. The increase in iPTH with age was seen whatever the values of 25
      hydroxyvitamin D, and was greater in the older persons. The concentration of iPTH
      rose continuously with effect from 25-hydroxyvitamin D values below ~30 ng/ml.
      Values above ~35 ng/ml were associated with a significantly lower concentration
      of iPTH. CONCLUSIONS: One-third (33.9%) of the Spanish population may be at risk
      for Vitamin D deficiency. The 25-hydroxyvitamin D values above 30 ng/ml can
      safely discard 'hyper PTH'. The increase in iPTH concentration is greater in
      older persons for similar values of 25-hydroxyvitamin D.

PMID- 21179053
TI  - Validation of a food frequency questionnaire to measure intakes of inulin and
      oligofructose.
AB  - BACKGROUND AND OBJECTIVES: Inulin and oligofructose are prebiotic carbohydrates
      associated with numerous health benefits. The aim of this study was to accurately
      measure inulin and oligofructose intakes and to develop and validate a food
      frequency questionnaire (FFQ). SUBJECTS AND METHODS: A 7-d semi-weighed food
      diary (FD) was used to measure intakes in 66 healthy subjects. A 23-item FFQ was
      developed to measure short-term inulin and oligofructose intakes over the same 7
      days and was completed twice on 2 separate days. RESULTS: There were no
      significant differences in inulin intake (4.0 +/- 1.3 vs 4.0 +/- 1.4 g/d, P =
      0.646) or oligofructose intake (3.8 +/- 1.2 vs 3.8 +/- 1.3 g/d, P = 0.864) when
      measured using the 7-d FD or the FFQ. Bland-Altman analysis demonstrated low mean
      differences between the FD and FFQ in measuring intakes of inulin (-0.09 g/d) and
      oligofructose (-0.03 g/d). The FFQ categorised 89% of subjects into the same or
      adjacent tertiles of intakes as the 7-d FD. For the majority of food items, kappa
      values indicated 'substantial' or 'almost perfect' agreement for assignment of
      'portion size' and 'frequency of consumption' between the FFQs completed on
      separate days. CONCLUSIONS: The FFQ is a valid and reliable method for measuring
      short-term inulin and oligofructose intakes for use in dietary surveys and
      clinical trials.

PMID- 21179054
TI  - Hematology: Bortezomib and dexamethasone induction for multiple myeloma.

PMID- 21179055
TI  - Endocytosis: Sorting the recycling.

PMID- 21179056
TI  - Mitosis: Good housekeeping.

PMID- 21179057
TI  - Protein synthesis: an expressive couple.

PMID- 21179058
TI  - Mechanisms of mitophagy.
AB  - Autophagy not only recycles intracellular components to compensate for nutrient
      deprivation but also selectively eliminates organelles to regulate their number
      and maintain quality control. Mitophagy, the specific autophagic elimination of
      mitochondria, has been identified in yeast, mediated by autophagy-related 32
      (Atg32), and in mammals during red blood cell differentiation, mediated by NIP3
      like protein X (NIX; also known as BNIP3L). Moreover, mitophagy is regulated in
      many metazoan cell types by parkin and PTEN-induced putative kinase protein 1
      (PINK1), and mutations in the genes encoding these proteins have been linked to
      forms of Parkinson's disease.

PMID- 21179059
TI  - Inventory control: cytochrome c oxidase assembly regulates mitochondrial
      translation.
AB  - Mitochondria maintain genome and translation machinery to synthesize a small
      subset of subunits of the oxidative phosphorylation system. To build up
      functional enzymes, these organellar gene products must assemble with imported
      subunits that are encoded in the nucleus. New findings on the early steps of
      cytochrome c oxidase assembly reveal how the mitochondrial translation of its
      core component, cytochrome c oxidase subunit 1 (Cox1), is directly coupled to the
      assembly of this respiratory complex.

PMID- 21179060
TI  - Open chromatin in pluripotency and reprogramming.
AB  - Pluripotent stem cells can be derived from embryos or induced from adult cells by
      reprogramming. They are unique among stem cells in that they can give rise to all
      cell types of the body. Recent findings indicate that a particularly 'open'
      chromatin state contributes to maintenance of pluripotency. Two principles are
      emerging: specific factors maintain a globally open chromatin state that is
      accessible for transcriptional activation; and other chromatin regulators
      contribute locally to the silencing of lineage-specific genes until
      differentiation is triggered. These same principles may apply during
      reacquisition of an open chromatin state upon reprogramming to pluripotency, and
      during de-differentiation in cancer.

PMID- 21179062
TI  - Genetics of cuticular hydrocarbon differences between males of the parasitoid
      wasps Nasonia giraulti and Nasonia vitripennis.
AB  - Many insects rely on cuticular hydrocarbons (CHCs) as major recognition signals
      between individuals. Previous research on the genetics of CHCs has focused on
      Drosophila in which the roles of three desaturases and one elongase were
      highlighted. Comparable studies in other insect taxa have not been conducted so
      far. Here, we explore the genetics of CHCs in hybrids of the jewel wasps Nasonia
      giraulti and Nasonia vitripennis. We analyzed the CHC profiles of pure strain and
      of F(2) hybrid males using gas chromatography coupled with mass spectrometry and
      distinguished 54 peaks, of which we identified 52 as straight-chain,
      monounsaturated, or methyl-branched CHCs. The latter compound class proved to be
      particularly abundant and diverse in Nasonia. Quantitative trait locus (QTL)
      analysis suggests fixed genetic differences between the two strains in 42 of the
      54 studied traits, making Nasonia a promising genetic model for identifying genes
      involved in CHC biosynthesis. QTL for methyl-branched CHCs partly clustered in
      genomic regions with high recombination rate: a possible indication for
      pleiotropic genes that control their biosynthesis, which is largely unexplored so
      far. Finally, we identified and mapped genes in the Nasonia genome with high
      similarity to genes that have been implicated in alkene biosynthesis in
      Drosophila and discuss those that match in their position with predicted QTL for
      alkenes.

PMID- 21179063
TI  - Are males the more 'sensitive' sex?

PMID- 21179061
TI  - A structural overview of the plasma membrane Na+,K+-ATPase and H+-ATPase ion
      pumps.
AB  - Plasma membrane ATPases are primary active transporters of cations that maintain
      steep concentration gradients. The ion gradients and membrane potentials derived
      from them form the basis for a range of essential cellular processes, in
      particular Na(+)-dependent and proton-dependent secondary transport systems that
      are responsible for uptake and extrusion of metabolites and other ions. The ion
      gradients are also both directly and indirectly used to control pH homeostasis
      and to regulate cell volume. The plasma membrane H(+)-ATPase maintains a proton
      gradient in plants and fungi and the Na(+),K(+)-ATPase maintains a Na(+) and K(+)
      gradient in animal cells. Structural information provides insight into the
      function of these two distinct but related P-type pumps.

PMID- 21179064
TI  - Effects of human perturbation on the genetic make-up of an island population: the
      case of the Sardinian wild boar.
AB  - Game species are often manipulated by human beings, whose activities can deeply
      affect their genetic make-up and population structure. We focused on a
      geographically isolated wild boar population (Sardinia, Italy), which is
      classified, together with the Corsican population, as a separate subspecies (Sus
      scrofa meridionalis). Two hundred and ten wild boars collected across Sardinia
      were analysed with a set of 10 microsatellites and compared with 296 reference
      genotypes from continental wild populations and to a sample of domestic pigs. The
      Sardinian population showed remarkable diversity and a high proportion of private
      alleles, and strongly deviated from the equilibrium. A Bayesian cluster analysis
      of only the Sardinian sample revealed a partition into five subpopulations.
      However, two different Bayesian approaches to the assignment of individuals,
      accounting for different possible source populations, produced consistent results
      and proved the admixed nature of the Sardinian population. Indeed, introgressive
      hybridization with boars from multiple sources (Italian peninsula, central
      Europe, domestic stocks) was detected, although poor evidence of crossbreeding
      with free-ranging domestic pigs was unexpectedly found. After excluding
      individuals who carried exotic genes, the population re-entered Hardy-Weinberg
      proportions and a clear population structure with three subpopulations emerged.
      Therefore, the inclusion of introgressed animals in the Bayesian analysis implied
      an overestimation of the number of clusters. Nonetheless, two of them were
      consistent between analyses and corresponded to highly pure stocks, located,
      respectively, in north-west and south-west Sardinia. This work shows the critical
      importance of including adequate reference samples when studying the genetic
      structure of managed wild populations.

PMID- 21179065
TI  - A locus-wide approach to assessing variation in the avian MHC: the B-locus of the
      wild turkey.
AB  - Studies of major histocompatibility complex (MHC) diversity in non-model
      vertebrates typically focus on structure and sequence variation in the antigen
      presenting loci: the highly variable and polymorphic class I and class IIB genes.
      Although these studies provide estimates of the number of genes and
      alleles/locus, they often overlook variation in functionally related and co
      inherited genes important in the immune response. This study utilizes the
      sequence of the MHC B-locus derived from a commercial turkey to investigate MHC
      variation in wild birds. Sequences were obtained for nine interspersed MHC
      amplicons (non-class I/II) from each of 40 birds representing 3 subspecies of
      wild turkey (Meleagris gallopavo). Analysis of aligned sequences identified 238
      single-nucleotide variants approximately one-third of which had minor allele
      frequencies >0.2 in the sampled birds. PHASE analysis identified 70 prospective
      MHC haplotypes in the wild turkeys, whereas a combined analysis with commercial
      birds identified almost 100 haplotypes in the species. Denaturing gradient gel
      electrophoresis (DGGE) of the class IIB loci was used to test the efficacy of
      single-nucleotide polymorphism (SNP) haplotyping to capture locus-wide variation.
      Diversity in SNP haplotypes and haplotype sharing among individuals was directly
      reflected in the DGGE patterns. Utilization of a reference haplotype to sequence
      interspersed regions of the MHC has significant advantages over other methods of
      surveying diversity while identifying high-frequency SNPs for genotyping. SNP
      haplotyping provides a means to identify both divergent haplotypes and homozygous
      individuals for assessment of immunological variation in wild and domestic
      populations.

PMID- 21179066
TI  - Splicing mutations in glycogen-storage disease type II: evaluation of the full
      spectrum of mutations and their relation to patients' phenotypes.
AB  - Glycogen-storage disease type II is an autosomal recessive-inherited disorder due
      to the deficiency of acid alpha-glucosidase. A large number of mutations in the
      acid alpha-glucosidase gene have been described to date. Among them, ~15% are
      variations that may affect mRNA splicing process. In this study, we have for the
      first time comprehensively reviewed the available information on splicing
      mutations of the acid alpha-glucosidase gene and we have evaluated their possible
      impact on the splicing process using different in silico approaches. Out of the
      39 different GAA-sequence variations described, an in silico analysis using seven
      different programs showed that 97% of them are predicted to have an impact on the
      splicing process. Moreover, this analysis showed a quite good correlation between
      the impact of the mutation on the splicing process and the clinical phenotype. In
      addition, we have performed the functional characterization of three novel
      sequence variants found in Italian patients and still uncharacterized. Using a
      minigene system, we have confirmed their pathogenic nature. In conclusion, this
      study has shown that in silico analysis represents a useful tool to select
      mutations that affect the splicing process of the acid alpha-glucosidase gene and
      provides an updated picture of all this kind of mutations reported till now.

PMID- 21179068
TI  - Temporal dynamics and spatial specificity of arterial and venous blood volume
      changes during visual stimulation: implication for BOLD quantification.
AB  - Determination of compartment-specific cerebral blood volume (CBV) changes is
      important for understanding neurovascular physiology and quantifying blood
      oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI).
      In isoflurane-anesthetized cats, we measured the spatiotemporal responses of
      arterial CBV (CBV(a)) and total CBV (CBV(t)) induced by a 40-second visual
      stimulation, using magnetization transfer (MT)-varied BOLD and contrast-agent
      fMRI techniques at 9.4 T. To determine the venous CBV (CBV(v)) change, we
      calculated the difference between CBV(t) and CBV(a) changes. The dynamic response
      of CBV(a) was an order of magnitude faster than that of CBV(v), while the
      magnitude of change under steady-state conditions was similar between the two.
      Following stimulation offset, DeltaCBV(a) showed small poststimulus undershoots,
      while DeltaCBV(v) slowly returned to baseline. The largest CBV(a) and CBV(t)
      response occurred after 10 seconds of simulation in cortical layer 4, which we
      identified as the stripe of Gennari by T(1)-weighted MRI. The CBV(v) response,
      however, was not specific across the cortical layers during the entire
      stimulation period. Our data indicate that rapid, more-specific arterial
      vasodilation is followed by slow, less-specific venous dilation. Our finding
      implies that the contribution of CBV(v) changes to BOLD signals is significant
      for long, but not short, stimulation periods.

PMID- 21179067
TI  - A candidate gene study of the type I interferon pathway implicates IKBKE and IL8
      as risk loci for SLE.
AB  - Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease in which the
      type I interferon pathway has a crucial role. We have previously shown that three
      genes in this pathway, IRF5, TYK2 and STAT4, are strongly associated with risk
      for SLE. Here, we investigated 78 genes involved in the type I interferon pathway
      to identify additional SLE susceptibility loci. First, we genotyped 896 single
      nucleotide polymorphisms in these 78 genes and 14 other candidate genes in 482
      Swedish SLE patients and 536 controls. Genes with P<0.01 in the initial screen
      were then followed up in 344 additional Swedish patients and 1299 controls. SNPs
      in the IKBKE, TANK, STAT1, IL8 and TRAF6 genes gave nominal signals of
      association with SLE in this extended Swedish cohort. To replicate these findings
      we extracted data from a genomewide association study on SLE performed in a US
      cohort. Combined analysis of the Swedish and US data, comprising a total of 2136
      cases and 9694 controls, implicates IKBKE and IL8 as SLE susceptibility loci
      (P(meta)=0.00010 and P(meta)=0.00040, respectively). STAT1 was also associated
      with SLE in this cohort (P(meta)=3.3 * 10-5), but this association signal appears
      to be dependent of that previously reported for the neighbouring STAT4 gene. Our
      study suggests additional genes from the type I interferon system in SLE, and
      highlights genes in this pathway for further functional analysis.

PMID- 21179069
TI  - Microvascular oxygen tension and flow measurements in rodent cerebral cortex
      during baseline conditions and functional activation.
AB  - Measuring cerebral oxygen delivery and metabolism microscopically is important
      for interpreting macroscopic functional magnetic resonance imaging (fMRI) data
      and identifying pathological changes associated with stroke, Alzheimer's disease,
      and brain injury. Here, we present simultaneous, microscopic measurements of
      cerebral blood flow (CBF) and oxygen partial pressure (pO(2)) in cortical
      microvessels of anesthetized rats under baseline conditions and during
      somatosensory stimulation. Using a custom-built imaging system, we measured CBF
      with Fourier-domain optical coherence tomography (OCT), and vascular pO(2) with
      confocal phosphorescence lifetime microscopy. Cerebral blood flow and pO(2)
      measurements displayed heterogeneity over distances irresolvable with fMRI and
      positron emission tomography. Baseline measurements indicate O(2) extraction from
      pial arterioles and homogeneity of ascending venule pO(2) despite large variation
      in microvessel flows. Oxygen extraction is linearly related to flow in ascending
      venules, suggesting that flow in ascending venules closely matches oxygen demand
      of the drained territory. Oxygen partial pressure and relative CBF transients
      during somatosensory stimulation further indicate arteriolar O(2) extraction and
      suggest that arterioles contribute to the fMRI blood oxygen level dependent
      response. Understanding O(2) supply on a microscopic level will yield better
      insight into brain function and the underlying mechanisms of various
      neuropathologies.

PMID- 21179070
TI  - Arterial spin labeling and dynamic susceptibility contrast CBF MRI in
      postischemic hyperperfusion, hypercapnia, and after mannitol injection.
AB  - Arterial spin labeling (ASL) and dynamic susceptibility contrast (DSC) magnetic
      resonance imaging (MRI) are widely used to image cerebral blood flow (CBF) in
      stroke. This study examined how changes in tissue spin-lattice relaxation-time
      constant (T(1)), blood-brain barrier (BBB) permeability, and transit time affect
      CBF quantification by ASL and DSC in postischemic hyperperfusion in the same
      animals. In Group I (n=6), embolic stroke rats imaged 48 hours after stroke
      showed regional hyperperfusion. In normal pixels, ASL- and DSC-CBF linearly
      correlated pixel-by-pixel. In hyperperfusion pixels, ASL-CBF was significantly
      higher than DSC-CBF pixel-by-pixel (by 25%). T(1) increased from 1.76+/-0.14
      seconds in normal pixels to 1.93+/-0.17 seconds in hyperperfusion pixels.
      Arterial transit time decreased from 300 milliseconds in normal pixels to 200
      milliseconds in hyperperfusion pixels. DeltaR(2)(*) profiles showed contrast
      agent leakages in the hyperperfusion regions. In Group II (n=3) in which
      hypercapnic inhalation was used to increase CBF without BBB disruption, CBF
      increased overall but ASL- and DSC-CBF remained linearly correlated. In Group III
      (n=3) in which mannitol was used to break the BBB, ASL-CBF was significantly
      higher than DSC-CBF. We concluded that in normal tissue, ASL and DSC provide
      comparable quantitative CBF, whereas in postischemic hyperperfusion, ASL-CBF and
      DSC-CBF differed significantly because ischemia-induced changes in T(1) and BBB
      permeability affected the two methods differently.

PMID- 21179071
TI  - Endothelium-dependent hyperpolarization: out of the dish and into the brain.

PMID- 21179072
TI  - Endothelial SK(Ca) and IK(Ca) channels regulate brain parenchymal arteriolar
      diameter and cortical cerebral blood flow.
AB  - Calcium-sensitive potassium (K(Ca)) channels have been shown to modulate the
      diameter of cerebral pial arteries; however, little is known regarding their
      roles in controlling cerebral parenchymal arterioles (PAs). We explored the
      function and cellular distribution of small-conductance (SK(Ca)) and intermediate
      conductance (IK(Ca)) K(Ca) channels and large-conductance K(Ca) (BK(Ca)) channels
      in endothelial cells (ECs) and smooth muscle cells (SMCs) of PAs. Both SK(Ca) and
      IK(Ca) channels conducted the outward current in isolated PA ECs (current
      densities, ~20 pA/pF and ~28 pA/pF at +40 mV, respectively), but these currents
      were not detected in PA SMCs. In contrast, BK(Ca) currents were prominent in PA
      SMCs (~154 pA/pF), but were undetectable in PA ECs. Pressurized PAs constricted
      to inhibition of SK(Ca) (~16%) and IK(Ca) (~16%) channels, but were only modestly
      affected by inhibition of BK(Ca) channels (~5%). Blockade of SK(Ca) and IK(Ca)
      channels decreased resting cortical cerebral blood flow (CBF) by ~15%. NS309 (6,7
      dichloro-1H-indole-2,3-dione3-oxime), a SK(Ca)/IK(Ca) channel opener,
      hyperpolarized PA SMCs by ~27 mV, maximally dilated pressurized PAs, and
      increased CBF by ~40%. In conclusion, these data show that SK(Ca) and IK(Ca)
      channels in ECs profoundly modulate PA tone and CBF, whereas BK(Ca) channels in
      SMCs only modestly influence PA diameter.

PMID- 21179074
TI  - The whole and the parts, development and aging, life and death.

PMID- 21179073
TI  - Anaerobic function of CNS white matter declines with age.
AB  - The mammalian central nervous system (CNS) is generally believed to be completely
      dependent on the presence of oxygen (O(2)) to maintain energy levels necessary
      for excitability. However, previous studies on CNS white matter (WM) have shown
      that a large subset of CNS-myelinated axons of mice aged 4 to 6 weeks remains
      excitable in the absence of O(2). We investigated whether this surprising WM
      tolerance to anoxia varied with age. Acutely isolated mouse optic nerve (MON), a
      purely myelinated WM tract, was studied electrophysiologically. Excitability in
      the MONs from 1-month-, 4-month-, and 8-month-old mice was assessed
      quantitatively as the area under the supramaximal compound action potential
      (CAP). Anoxia-resistant WM function declined with age. After 60  minutes of
      anoxia, ~23% of the CAP remained in 1-month-old mice, 8% in 4-month-old mice, and
      ~0 in the 8-month-old group. Our results indicated that although some CNS axons
      function anaerobically in young adult animals, they lose this ability in later
      adulthood. This finding may help explain the clinical impression that favorable
      outcome after stroke and other brain injuries declines with age.

PMID- 21179075
TI  - Nutrigenomics.

PMID- 21179076
TI  - Health: Edible advice.

PMID- 21179077
TI  - Diversity: Of beans and genes.

PMID- 21179078
TI  - History: The changing notion of food.

PMID- 21179079
TI  - Taste: More than meets the mouth.

PMID- 21179080
TI  - Interdisciplinary research: Big science at the table.

PMID- 21179081
TI  - Epigenetics: Tales of adversity.

PMID- 21179082
TI  - Technology: A flavour of the future.

PMID- 21179083
TI  - Development: Mother's milk: A rich opportunity.

PMID- 21179084
TI  - Evolution: The first supper.

PMID- 21179085
TI  - Cortical representations of olfactory input by trans-synaptic tracing.
AB  - In the mouse, each class of olfactory receptor neurons expressing a given odorant
      receptor has convergent axonal projections to two specific glomeruli in the
      olfactory bulb, thereby creating an odour map. However, it is unclear how this
      map is represented in the olfactory cortex. Here we combine rabies-virus
      dependent retrograde mono-trans-synaptic labelling with genetics to control the
      location, number and type of 'starter' cortical neurons, from which we trace
      their presynaptic neurons. We find that individual cortical neurons receive input
      from multiple mitral cells representing broadly distributed glomeruli. Different
      cortical areas represent the olfactory bulb input differently. For example, the
      cortical amygdala preferentially receives dorsal olfactory bulb input, whereas
      the piriform cortex samples the whole olfactory bulb without obvious bias. These
      differences probably reflect different functions of these cortical areas in
      mediating innate odour preference or associative memory. The trans-synaptic
      labelling method described here should be widely applicable to mapping
      connections throughout the mouse nervous system.

PMID- 21179086
TI  - Evidence for a spin-aligned neutron-proton paired phase from the level structure
      of (92)Pd.
AB  - Shell structure and magic numbers in atomic nuclei were generally explained by
      pioneering work that introduced a strong spin-orbit interaction to the nuclear
      shell model potential. However, knowledge of nuclear forces and the mechanisms
      governing the structure of nuclei, in particular far from stability, is still
      incomplete. In nuclei with equal neutron and proton numbers (N = Z), enhanced
      correlations arise between neutrons and protons (two distinct types of fermions)
      that occupy orbitals with the same quantum numbers. Such correlations have been
      predicted to favour an unusual type of nuclear superfluidity, termed isoscalar
      neutron-proton pairing, in addition to normal isovector pairing. Despite many
      experimental efforts, these predictions have not been confirmed. Here we report
      the experimental observation of excited states in the N = Z = 46 nucleus (92)Pd.
      Gamma rays emitted following the (58)Ni((36)Ar,2n)(92)Pd fusion-evaporation
      reaction were identified using a combination of state-of-the-art high-resolution
      gamma-ray, charged-particle and neutron detector systems. Our results reveal
      evidence for a spin-aligned, isoscalar neutron-proton coupling scheme, different
      from the previous prediction. We suggest that this coupling scheme replaces
      normal superfluidity (characterized by seniority coupling) in the ground and low
      lying excited states of the heaviest N = Z nuclei. Such strong, isoscalar neutron
      proton correlations would have a considerable impact on the nuclear level
      structure and possibly influence the dynamics of rapid proton capture in stellar
      nucleosynthesis.

PMID- 21179087
TI  - Oncogenically active MYD88 mutations in human lymphoma.
AB  - The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL)
      remains the least curable form of this malignancy despite recent advances in
      therapy. Constitutive nuclear factor (NF)-kappaB and JAK kinase signalling
      promotes malignant cell survival in these lymphomas, but the genetic basis for
      this signalling is incompletely understood. Here we describe the dependence of
      ABC DLBCLs on MYD88, an adaptor protein that mediates toll and interleukin (IL)-1
      receptor signalling, and the discovery of highly recurrent oncogenic mutations
      affecting MYD88 in ABC DLBCL tumours. RNA interference screening revealed that
      MYD88 and the associated kinases IRAK1 and IRAK4 are essential for ABC DLBCL
      survival. High-throughput RNA resequencing uncovered MYD88 mutations in ABC DLBCL
      lines. Notably, 29% of ABC DLBCL tumours harboured the same amino acid
      substitution, L265P, in the MYD88 Toll/IL-1 receptor (TIR) domain at an
      evolutionarily invariant residue in its hydrophobic core. This mutation was rare
      or absent in other DLBCL subtypes and Burkitt's lymphoma, but was observed in 9%
      of mucosa-associated lymphoid tissue lymphomas. At a lower frequency, additional
      mutations were observed in the MYD88 TIR domain, occurring in both the ABC and
      germinal centre B-cell-like (GCB) DLBCL subtypes. Survival of ABC DLBCL cells
      bearing the L265P mutation was sustained by the mutant but not the wild-type
      MYD88 isoform, demonstrating that L265P is a gain-of-function driver mutation.
      The L265P mutant promoted cell survival by spontaneously assembling a protein
      complex containing IRAK1 and IRAK4, leading to IRAK4 kinase activity, IRAK1
      phosphorylation, NF-kappaB signalling, JAK kinase activation of STAT3, and
      secretion of IL-6, IL-10 and interferon-beta. Hence, the MYD88 signalling pathway
      is integral to the pathogenesis of ABC DLBCL, supporting the development of
      inhibitors of IRAK4 kinase and other components of this pathway for the treatment
      of tumours bearing oncogenic MYD88 mutations.

PMID- 21179088
TI  - Preplay of future place cell sequences by hippocampal cellular assemblies.
AB  - During spatial exploration, hippocampal neurons show a sequential firing pattern
      in which individual neurons fire specifically at particular locations along the
      animal's trajectory (place cells). According to the dominant model of hippocampal
      cell assembly activity, place cell firing order is established for the first time
      during exploration, to encode the spatial experience, and is subsequently
      replayed during rest or slow-wave sleep for consolidation of the encoded
      experience. Here we report that temporal sequences of firing of place cells
      expressed during a novel spatial experience occurred on a significant number of
      occasions during the resting or sleeping period preceding the experience. This
      phenomenon, which is called preplay, occurred in disjunction with sequences of
      replay of a familiar experience. These results suggest that internal neuronal
      dynamics during resting or sleep organize hippocampal cellular assemblies into
      temporal sequences that contribute to the encoding of a related novel experience
      occurring in the future.

PMID- 21179089
TI  - Comprehensive analysis of the chromatin landscape in Drosophila melanogaster.
AB  - Chromatin is composed of DNA and a variety of modified histones and non-histone
      proteins, which have an impact on cell differentiation, gene regulation and other
      key cellular processes. Here we present a genome-wide chromatin landscape for
      Drosophila melanogaster based on eighteen histone modifications, summarized by
      nine prevalent combinatorial patterns. Integrative analysis with other data (non
      histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by
      engaged polymerase, short/long RNA products) reveals discrete characteristics of
      chromosomes, genes, regulatory elements and other functional domains. We find
      that active genes display distinct chromatin signatures that are correlated with
      disparate gene lengths, exon patterns, regulatory functions and genomic contexts.
      We also demonstrate a diversity of signatures among Polycomb targets that include
      a subset with paused polymerase. This systematic profiling and integrative
      analysis of chromatin signatures provides insights into how genomic elements are
      regulated, and will serve as a resource for future experimental investigations of
      genome structure and function.

PMID- 21179092
TI  - Chemistry on a global stage. The international year of chemistry gives chemists a
      chance to raise the profile of their subject.

PMID- 21179091
TI  - A TALE nuclease architecture for efficient genome editing.
AB  - Nucleases that cleave unique genomic sequences in living cells can be used for
      targeted gene editing and mutagenesis. Here we develop a strategy for generating
      such reagents based on transcription activator-like effector (TALE) proteins from
      Xanthomonas. We identify TALE truncation variants that efficiently cleave DNA
      when linked to the catalytic domain of FokI and use these nucleases to generate
      discrete edits or small deletions within endogenous human NTF3 and CCR5 genes at
      efficiencies of up to 25%. We further show that designed TALEs can regulate
      endogenous mammalian genes. These studies demonstrate the effective application
      of designed TALE transcription factors and nucleases for the targeted regulation
      and modification of endogenous genes.

PMID- 21179093
TI  - Science in the service of citizens and consumers.

PMID- 21179090
TI  - The developmental transcriptome of Drosophila melanogaster.
AB  - Drosophila melanogaster is one of the most well studied genetic model organisms;
      nonetheless, its genome still contains unannotated coding and non-coding genes,
      transcripts, exons and RNA editing sites. Full discovery and annotation are pre
      requisites for understanding how the regulation of transcription, splicing and
      RNA editing directs the development of this complex organism. Here we used RNA
      Seq, tiling microarrays and cDNA sequencing to explore the transcriptome in 30
      distinct developmental stages. We identified 111,195 new elements, including
      thousands of genes, coding and non-coding transcripts, exons, splicing and
      editing events, and inferred protein isoforms that previously eluded discovery
      using established experimental, prediction and conservation-based approaches.
      These data substantially expand the number of known transcribed elements in the
      Drosophila genome and provide a high-resolution view of transcriptome dynamics
      throughout development.

PMID- 21179095
TI  - Scanning tunnelling microscopy: closing in on molecular junctions.

PMID- 21179096
TI  - Nanoelectronics: graphene gets a better gap.

PMID- 21179097
TI  - Quantum computing: Solid-state spins survive.

PMID- 21179098
TI  - Nanobiotechnology: nanoparticle coronas take shape.

PMID- 21179099
TI  - Chronic blockade of the (pro)renin receptor ameliorates the kidney damage in the
      non-clipped kidney of Goldblatt hypertension.

PMID- 21179100
TI  - Association of elevated inflammatory and endothelial biomarkers with
      prehypertension among Mongolians in China.
AB  - Chronic inflammation and endothelial dysfunction may be associated with
      hypertension and cardiovascular disease. We examined associations between
      inflammatory and endothelial dysfunction biomarkers and the risk of
      prehypertension among Mongolians. A cross-sectional study was conducted among
      2589 Mongolians aged 20 years and older in Inner Mongolia, China. Three blood
      pressure measurements, body weight, height and lifestyle factors were obtained
      for all participants. Overnight fasting blood samples were obtained to measure
      the biomarkers, including C-reactive protein (CRP), soluble intercellular
      adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin) and angiotensin
      II. The average levels of CRP (7.43 vs. 5.86), sICAM-1 (339.38 vs. 328.05), sE
      selectin (19.11 vs. 18.32) and angiotensin II (52.00 vs. 47.00) were all
      significantly higher in hypertensives than that in prehypertensives (all P<0.05);
      prehypertensives had higher levels of CRP (5.86 vs. 4.85) and sICAM-1 (328.05 vs.
      314.14) compared with normotensives (both P<0.05). Hypertension (odds ratio (OR):
      1.50, 95% confidence interval (CI): 1.07, 2.11) and prehypertension (OR: 1.38,
      95% CI: 1.02, 1.85) were positively and significantly associated with elevated
      CRP adjusted for multivariable. Hypertension (OR: 1.56, 95% CI: 1.18, 2.06) and
      prehypertension (OR: 1.32, 95% CI: 1.02, 1.71) were also positively and
      significantly associated with higher sICAM-1 adjusted for age and gender.
      Elevated CRP and sICAM-1 were associated with prehypertension among Mongolian
      population. This study suggests that inflammation and endothelial dysfunction may
      have a role in the development of hypertension.

PMID- 21179101
TI  - Fibrinolysis and insulin sensitivity in imidapril and candesartan (FISIC study)
      recipients with hypertension.
AB  - The aim of this study was to evaluate the effects of imidapril and candesartan on
      fibrinolysis and insulin sensitivity in normoweight hypertensive patients. After
      a 2-week wash-out period, 61 patients with mild-to-moderate hypertension were
      randomized to imidapril or candesartan for 12 weeks. Blood pressure (BP), plasma
      tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1)
      antigen activities were evaluated at baseline and during treatment. The patients
      underwent a euglycemic-hyperinsulinemic clamp (insulin sensitivity was evaluated
      as glucose infusion rate during the last 30 min) and a desmopressin test (with
      desmopressin infusion in the brachial artery) to evaluate endothelial ability to
      release t-PA. Imidapril and candesartan induced similar systolic/diastolic BP
      reductions (-16/12.6 and -16.1/12.2 mm Hg, respectively, P<0.001 vs. baseline).
      Imidapril increased glucose infusion rate (+1.1 mg min(-1) per kg, P<0.02),
      whereas candesartan did not change it. Both drugs decreased PAI-1 antigen
      activity after 4 weeks of treatment; subsequently, only the decreasing effect of
      imidapril was sustained throughout the 12 weeks, whereas candesartan increased
      PAI-1 activity at week 12 (P<0.05 vs. baseline, P<0.01 vs. imidapril). Activity
      of t-PA decreased with candesartan (from 0.48+/-0.16 to 0.43+/-0.14 IU ml(-1),
      P<0.05) but not with imidapril. Activity of t-PA in response to desmopressin was
      increased more by imidapril (+4.45 IU ml(-1)) than by candesartan (+2.73 IU ml(
      1), P<0.01 vs. imidapril). These results indicate that in normoweight
      hypertensive patients, despite similar BP reduction, imidapril but not
      candesartan improved the fibrinolytic balance, suggesting that mechanisms other
      than Ang II inhibition, possibly including bradykinin-mediated effects on insulin
      sensitivity and endothelial function, may be responsible for these different
      effects.

PMID- 21179102
TI  - Association of ADAM33 gene polymorphisms with asthma in Indian children.
AB  - Asthma is the most common chronic disorder in childhood, and asthma exacerbation
      is an important cause of childhood morbidity and hospitalization. In the present
      study, the relationship between single-nucleotide polymorphisms (SNPs) of the
      ADAM33 gene and asthma in Indian children has been examined using a case-control
      study. Five SNPs of the ADAM33 gene, F+1(rs511898) G/A, S2 (rs528557) G/C, ST+4
      (rs44707) A/C, ST+5 (rs597980) C/T and V4 (rs2787094) C/G, were analyzed in 211
      asthma cases and 137 controls aged 1-15 years using the PCR-restriction fragment
      length polymorphism method. Data were statistically analyzed using the chi(2)
      test and logistic regression model. Haplotype estimation and linkage
      disequilibrium were conducted using the expectation-maximization algorithm. The
      genotypes and allele frequencies of SNPs S2 and ST+5 of the ADAM33 gene were
      significantly associated with asthma risk (P = 0.020 - < 0.001), whereas F+1,
      ST+4, V4 homozygous mutant genotypes and mutant alleles were significantly
      associated with increased asthma risk (P = 0.031 - < 0.001). A positive
      association was also found with haplotypes AGCCT, GGACT and AGCCC (P = < 0.001,
      odds ratio (OR) = 6.10-6.50), whereas ACAGT, AGCGC, AGCGT, GCAGC and GCCGT showed
      protective association with asthma (P = 0.019-0.000, OR = 0.50-0.20). Taken
      together, out results suggest that ADAM33 gene polymorphisms may modify
      individual susceptibility to develop childhood asthma in the Indian population.

PMID- 21179104
TI  - Prevalence of c.1559delT in ALPL, a common mutation resulting in the perinatal
      (lethal) form of hypophosphatasia in Japanese and effects of the mutation on
      heterozygous carriers.
AB  - Hypophosphatasia (HPP) is an inherited disorder caused by mutations in ALPL that
      encodes an isozyme of alkaline phosphatase (ALP), TNSALP. One of the most
      frequent ALPL mutations is c.1559delT, which causes the most severe HPP, the
      perinatal (lethal) form (pl-HPP). c.1559delT has been found only in Japanese and
      its prevalence is suspected to be high; however, the allele frequency of
      c.1559delT in Japanese remains unknown. We designed a screening system for the
      mutation based on high-resolution melting curve analysis, and examined the
      frequency of c.1559delT. We found that the c.1559delT carrier frequency is 1/480
      (95% confidence interval, 1/1562-1/284). This indicates that ~1 in 900 000
      individuals to have pl-HPP caused by a homozygous c.1559delT mutation. In our
      analysis, the majority of c.1559delT carriers had normal values of HPP
      biochemical markers, such as serum ALP and urine phosphoethanolamine. Our results
      indicate that the only way to reliably detect whether individuals are pl-HPP
      carriers is to perform the ALPL mutation analysis.

PMID- 21179103
TI  - Positive selection on mitochondrial M7 lineages among the Gelong people in
      Hainan.
AB  - Selections on human mitochondrial variations are difficult to examine. In this
      study, we found possible signs of selection on mitochondrial M7 lineages among
      the Gelong people who migrated from Guizhou to Hainan (the hottest province in
      China) throughout the last 1000 years. The genetic structure of the Gelong people
      shows an obvious sex-biased population admixture pattern with only 4.9% paternal
      contribution but 30.7% maternal contribution from indigenous Hlai people.
      According to frequency spectrum tests for deviation from neutrality and mismatch
      tests of demographic expansion, part of the maternal mitochondrial M7 lineages
      among the Gelong came from the Hlai had spread quickly and therefore might have
      undergone positive selection. In the future, whole mitochondrial genome
      sequencing might reveal the functional advantage of the M7 lineages.

PMID- 21179105
TI  - Familial Mediterranean fever with a single MEFV mutation: can a deletion
      resulting in alpha-thalassemia be the cause?

PMID- 21179106
TI  - Association of HLA-A*02:06 and HLA-DRB1*04:05 with clinical subtypes of juvenile
      idiopathic arthritis.
AB  - Juvenile idiopathic arthritis (JIA) is one of the most common forms of pediatric
      chronic arthritis. JIA is a clinically heterogeneous disease. Therefore, the
      genetic background of JIA may also be heterogeneous. The aim of this study was to
      investigate associations between human leukocyte antigen (HLA) and susceptibility
      to JIA and/or uveitis, which is one of the most devastating complications of JIA.
      A total of 106 Japanese articular JIA patients (67 with polyarthritis and 39 with
      oligoarthritis) and 678 healthy controls were genotyped for HLA-A, -B and -DRB1
      by PCR-sequence-specific oligonucleotide probe methodology. HLA-A(*)02:06 was the
      risk factor for JIA accompanied by uveitis after adjustment for clinical factors
      (corrected P-value < 0.001, odds ratio (OR) 11.7, 95% confidence interval (CI)
      3.2-43.0). On the other hand, HLA-DRB1(*)04:05 was associated with polyarticular
      JIA (corrected P-value < 0.001, OR 2.9, 95% CI 1.7-4.8). We found an association
      of HLA-A(*)02:06 with susceptibility to JIA accompanied by uveitis, which might
      be considered a separate clinical JIA entity. We also found an association
      between HLA-DRB1(*)04:05 and polyarticular JIA. Thus, clinical subtypes of JIA
      can be classified by the presence of the specific HLA alleles, HLA-A(*)02:06 and
      DRB1(*)04:05.

PMID- 21179107
TI  - A Japanese case of ichthyosis follicularis with atrichia and photophobia syndrome
      with an MBTPS2 mutation.
AB  - Ichthyosis follicularis with atrichia and photophobia (IFAP) syndrome is a rare
      genetic disorder characterized by the triad of ichthyosis follicularis, alopecia
      and photophobia. Previous studies have identified five missense mutations in the
      membrane-bound transcription factor protease, site 2 (MBTPS2) gene in European
      patients with this syndrome. In this study, we detected the 1286G > A (Arg429His)
      mutation in MBTPS2 in a Japanese patient with IFAP syndrome. This mutation has
      previously been detected in a German family with this syndrome. Functional
      analysis revealed that this mutation was the most severe mutation identified to
      date for this syndrome. None of the male German patients had been tested for the
      mutation because they had several visceral and bone anomalies, and had died as
      neonates or infants. The clinical features of our 5-year-old patient are less
      severe than those of the German patients. Although he has neurological
      abnormalities, such as retarded psychomotor development and seizures, he does not
      have bone or visceral anomalies, except cryptorchidism. This case indicates the
      existence of other factor(s) that influence the clinical features of this
      syndrome. Further clinical and genetic studies are required to clarify the
      relationship between phenotypes and genotypes and to identify such modifying
      factors.

PMID- 21179109
TI  - Stopwatch-assessed duration of erection: a new measure of the efficacy of
      erectile dysfunction treatments.
AB  - Results are reported from the first two adequate trials of the PDE-5 inhibitor
      vardenafil using a stopwatch to precisely measure erection duration in men with
      ED. Two randomized, multicenter, double-blind, placebo-controlled trials were
      conducted: a crossover 4-week treatment in men with ED (ENDURANCE) and a parallel
      group, 12-week treatment in men with ED and dyslipidemia (the dyslipidemia
      study). Stopwatch-assessed duration of erection leading to successful intercourse
      measured by Sexual Encounter Profile question-3 (SEP-3) was the primary end point
      in ENDURANCE and one of the secondary end points in the dyslipidemia study. Other
      efficacy end points included responses to SEP-2, SEP-3 and International Index of
      Erectile Function-Erectile Function (IIEF-EF) domain scores. Adverse events were
      recorded. Duration of erection (least squares mean +/- s.e.) leading to
      successful intercourse was statistically superior in men receiving vardenafil
      versus placebo (12.8 +/- 1.0 versus 5.5 +/- 1.0 min; p<0.001 in ENDURANCE and
      10.0 +/- 0.8 versus 3.4 +/- 0.8; p<0.001 in the dyslipidemia study), with a
      difference of 7.4 and 6.6 min, respectively, between treatment groups. Results
      for SEP-2, SEP-3 and IIEF-EF domain scores were consistent across studies and
      with stopwatch-assessed measures for duration of erection. Vardenafil was well
      tolerated. Duration of erection leading to successful intercourse is an important
      indicator of the efficacy of ED treatment. The stopwatch approach offers an
      alternative, precise and reproducible measure of efficacy. We propose this
      approach as a potential new paradigm for assessing the efficacy of ED treatments.

PMID- 21179108
TI  - Knowledge gaining by human genetic studies on tuberculosis susceptibility.
AB  - Tuberculosis (TB) is a serious health issue in the developing world. Lack of
      knowledge on the etiological mechanisms of TB hinders the development of
      effective strategies for the treatment or prevention of TB disease. Human genetic
      study is an indispensable approach to understand the molecular basis of common
      diseases. Numerous efforts were made to screen the human genome for TB
      susceptibility by linkage mapping. A large number of candidate-based association
      studies of TB were conducted to examine the association of predicted functional
      DNA variations in candidate genes. Recently, the first genome-wide association
      study (GWAS) on TB was reported. The GWAS is a proof-of-principle evidence that
      justifies the genetic approach to understand TB. Further hypothesis-free efforts
      on TB research may renovate the traditional idea of TB genetic susceptibility as
      none of the candidate genes with important roles in containing Mycobacterium
      tuberculosis (MTB) infection was identified of association with active TB,
      whereas the TB-associated loci in the GWAS harbors no gene with function in MTB
      infection.

PMID- 21179110
TI  - Bone morphogenetic protein 5 regulates the number of keratinocyte stem cells from
      the skin of mice.
AB  - Understanding keratinocyte stem cell regulation is important in understanding the
      pathogenesis of wound healing and nonmelanoma skin cancer. We previously used a
      sensitive and quantitative assay for in vitro keratinocyte colony formation and
      mapped the keratinocyte stem cell locus (Ksc1) on mouse chromosome 9. Examination
      of the candidate genes in this locus disclosed a sequence variant in the gene for
      bone morphogenetic protein 5 (Bmp5). In this report, we used a naturally
      occurring mouse with a null mutation in this gene to probe stem cell properties
      in mouse epidermis. We found that the mutant keratinocytes had a significant
      reduction in the size and number of clonogenic keratinocytes. The mutant mice had
      a 50% reduction in the number of label-retaining cells when compared with their
      littermates. Addition of exogenous Bmp5 protein increased the number and size of
      keratinocyte colonies in the mutant as well as their wild-type littermates.
      Surprisingly, the mutant mice showed at least a 2-fold increase in skin tumor
      susceptibility over their littermates. We conclude that a naturally occurring
      mutation in Bmp5 affects keratinocyte stem cell proliferation, and skin tumor
      susceptibility, and is a candidate stem cell regulatory gene in the Ksc1 locus.

PMID- 21179111
TI  - Angioid streaks in Pseudoxanthoma Elasticum: role of the p.R1268Q mutation in the
      ABCC6 gene.

PMID- 21179112
TI  - Exploring the CLEC16A gene reveals a MS-associated variant with correlation to
      the relative expression of CLEC16A isoforms in thymus.
AB  - Genomewide association studies have implicated the CLEC16A gene in several
      autoimmune diseases, including multiple sclerosis (MS) and type 1 diabetes.
      However, the most associated single-nucleotide polymorphism (SNP) varies, and
      causal variants are still to be defined. In MS, two SNPs in partial linkage
      disequilibrium with each other, rs6498169 and rs12708716, have been validated at
      genomewide significance level. To explore the CLEC16A association in MS in more
      detail, we genotyped 57 SNPs in 807 Norwegian MS patients and 1027 Norwegian
      controls. Six highly associated SNPs emerged and were then replicated in two
      large independent sample sets (Norwegian and British), together including 1153 MS
      trios, 2308 MS patients and 4044 healthy controls. In combined analyses, SNP
      rs12708716 gave the strongest association signal in MS (P=5.3 x 10-8, odds ratio
      1.18, 95% confidence interval=1.11-1.25), and was found to be superior to the
      other SNP associations in conditional logistic regression analyses. Expression
      analysis revealed that rs12708716 genotype was significantly associated with the
      relative expression levels of two different CLEC16A transcripts in thymus
      (P=0.004), but not in blood, possibly implying a thymus- or cell-specific splice
      regulation.

PMID- 21179114
TI  - A genome-wide admixture scan for ancestry-linked genes predisposing to
      sarcoidosis in African-Americans.
AB  - Genome-wide linkage and association studies have uncovered variants associated
      with sarcoidosis, a multiorgan granulomatous inflammatory disease. African
      ancestry may influence disease pathogenesis, as African-Americans are more
      commonly affected by sarcoidosis. Therefore, we conducted the first sarcoidosis
      genome-wide ancestry scan using a map of 1384 highly ancestry-informative single
      nucleotide polymorphisms genotyped on 1357 sarcoidosis cases and 703 unaffected
      controls self-identified as African-American. The most significant ancestry
      association was at marker rs11966463 on chromosome 6p22.3 (ancestry association
      risk ratio (aRR)=1.90; P=0.0002). When we restricted the analysis to biopsy
      confirmed cases, the aRR for this marker increased to 2.01; P=0.00007. Among the
      eight other markers that demonstrated suggestive ancestry associations with
      sarcoidosis were rs1462906 on chromosome 8p12, which had the most significant
      association with European ancestry (aRR=0.65; P=0.002), and markers on
      chromosomes 5p13 (aRR=1.46; P=0.005) and 5q31 (aRR=0.67; P=0.005), which
      correspond to regions we previously identified through sib-pair linkage analyses.
      Overall, the most significant ancestry association for Scadding stage IV cases
      was to marker rs7919137 on chromosome 10p11.22 (aRR=0.27; P=2 * 10(-5)), a region
      not associated with disease susceptibility. In summary, through admixture mapping
      of sarcoidosis we have confirmed previous genetic linkages and identified several
      novel putative candidate loci for sarcoidosis.

PMID- 21179115
TI  - Characterization of the macrophage transcriptome in glomerulonephritis
      susceptible and -resistant rat strains.
AB  - Crescentic glomerulonephritis (CRGN) is a major cause of rapidly progressive
      renal failure for which the underlying genetic basis is unknown. Wistar-Kyoto
      (WKY) rats show marked susceptibility to CRGN, whereas Lewis rats are resistant.
      Glomerular injury and crescent formation are macrophage dependent and mainly
      explained by seven quantitative trait loci (Crgn1-7). Here, we used microarray
      analysis in basal and lipopolysaccharide (LPS)-stimulated macrophages to identify
      genes that reside on pathways predisposing WKY rats to CRGN. We detected 97 novel
      positional candidates for the uncharacterized Crgn3-7. We identified 10
      additional secondary effector genes with profound differences in expression
      between the two strains (>5-fold change, <1% false discovery rate) for basal and
      LPS-stimulated macrophages. Moreover, we identified eight genes with
      differentially expressed alternatively spliced isoforms, by using an in-depth
      analysis at the probe level that allowed us to discard false positives owing to
      polymorphisms between the two rat strains. Pathway analysis identified several
      common linked pathways, enriched for differentially expressed genes, which affect
      macrophage activation. In summary, our results identify distinct macrophage
      transcriptome profiles between two rat strains that differ in susceptibility to
      glomerulonephritis, provide novel positional candidates for Crgn3-7 and define
      groups of genes that play a significant role in differential regulation of
      macrophage activity.

PMID- 21179116
TI  - An autoimmune-associated variant in PTPN2 reveals an impairment of IL-2R
      signaling in CD4(+) T cells.
AB  - The IL-2/IL-2R signaling pathway has an important role in autoimmunity. Several
      genes identified in genome-wide association (GWA) studies encode proteins in the
      IL-2/IL-2R signaling cascade that are associated with autoimmune diseases. One of
      these, PTPN2, encodes a protein tyrosine phosphatase that is highly expressed in
      T cells and regulates cytokine signaling. An intronic risk allele in PTPN2,
      rs1893217(C), correlated with decreased IL-2R signaling in CD4(+) T cells as
      measured by phosphorylation of STAT5 (phosphorylated STAT5 (pSTAT5)). We modeled
      an additive single nucleotide polymorphism (SNP) genotype, in which each copy of
      the risk allele conferred a decrease in IL-2R signaling (P=4.4 * 10(-8)).
      Decreased pSTAT5 impacted IL-2Rbeta chain signaling resulting in reduced FOXP3
      expression in activated cells. This phenotype was not due to overt differences in
      expression of the IL-2R, molecules in the IL-2R signaling cascade or defects in
      STAT5. However, the rs1893217(C) risk variant did correlate with decreased PTPN2
      expression in CD4(+)CD45RO T cells (P=0.0002). Thus, the PTPN2rs1893217(C) risk
      allele associated with reduced pSTAT5 in response to IL-2 and reduced PTPN2
      expression. Together, these data suggest that decreased expression of PTPN2 may
      indirectly modulate IL-2 responsiveness. These findings, identified through
      genotype/phenotype relationships, may lead to identification of novel mechanisms
      underlying dysregulation of cytokine signaling in autoimmunity.

PMID- 21179117
TI  - HLA (A-B-C and -DRB1) alleles and brain MRI changes in multiple sclerosis: a
      longitudinal study.
AB  - Several major histocompatibility complex (MHC) alleles have been postulated to
      influence the susceptibility to multiple sclerosis (MS), as well as its
      clinical/radiological course. In this longitudinal observation, we further
      explored the impact of human leukocyte antigen (HLA) class I/II alleles on MS
      outcomes, and we tested the hypothesis that HLA DRB1*1501 might uncover different
      strata of MS subjects harboring distinct MHC allele associations with magnetic
      resonance imaging (MRI) measures. Five hundred eighteen MS patients with two
      digit HLA typing and at least one brain MRI were recruited for the study. T2
      weighted hyperintense lesion volume (T2LV) and brain parenchymal fraction (BPF)
      were acquired at each time point. The association between allele count and MRI
      values was determined using linear regression modeling controlling for age,
      disease duration and gender. Analyses were also stratified by the
      presence/absence of HLA DRB1*1501. HLA DRB1*04 was associated with higher T2LV
      (P=0.006); after stratification, its significance remained only in the presence
      of HLA DRB1*1501 (P=0.012). The negative effect of HLA DRB1*14 on T2LV was
      exerted in DRB1*1501-negative group (P=0.012). Longitudinal analysis showed that
      HLA DRB1*10 was significantly protective on T2LV accrual in the presence of HLA
      DRB1*1501 (P=0.002). Although the majority of our results did not withstand
      multiple comparison correction, the differential impact of several HLA alleles in
      the presence/absence of HLA DRB1*1501 suggests that they may interact in
      determining the different phenotypic expressions of MS.

PMID- 21179120
TI  - Turbines and turbulence.

PMID- 21179121
TI  - Assessment time.

PMID- 21179118
TI  - Imaging techniques for assaying lymphocyte activation in action.
AB  - Imaging techniques have greatly improved our understanding of lymphocyte
      activation. Technical advances in spatial and temporal resolution and new
      labelling tools have enabled researchers to directly observe the activation
      process. Consequently, research using imaging approaches to study lymphocyte
      activation has expanded, providing an unprecedented level of cellular and
      molecular detail in the field. As a result, certain models of lymphocyte
      activation have been verified, others have been revised and yet others have been
      replaced with new concepts. In this article, we review the current imaging
      techniques that are used to assess lymphocyte activation in different contexts,
      from whole animals to single molecules, and discuss the advantages and potential
      limitations of these methods.

PMID- 21179122
TI  - Save university arts from the bean counters.

PMID- 21179119
TI  - Experimental human challenge infections can accelerate clinical malaria vaccine
      development.
AB  - Malaria is one of the most frequently occurring infectious diseases worldwide,
      with almost 1 million deaths and an estimated 243 million clinical cases
      annually. Several candidate malaria vaccines have reached Phase IIb clinical
      trials, but results have often been disappointing. As an alternative to these
      Phase IIb field trials, the efficacy of candidate malaria vaccines can first be
      assessed through the deliberate exposure of participants to the bites of
      infectious mosquitoes (sporozoite challenge) or to an inoculum of blood-stage
      parasites (blood-stage challenge). With an increasing number of malaria vaccine
      candidates being developed, should human malaria challenge models be more widely
      used to reduce cost and time investments? This article reviews previous
      experience with both the sporozoite and blood-stage human malaria challenge
      models and provides future perspectives for these models in malaria vaccine
      development.

PMID- 21179135
TI  - Integrity policy unveiled at last.

PMID- 21179137
TI  - UK science faces facilities freeze.

PMID- 21179138
TI  - Love thy lab neighbour.

PMID- 21179139
TI  - 2010 Gallery: images of the year.

PMID- 21179140
TI  - Fossil genome reveals ancestral link.

PMID- 21179141
TI  - Deep lab denied funding.

PMID- 21179142
TI  - 2010: The year in which ....

PMID- 21179143
TI  - Newsmaker of the year: In the eye of the storm.

PMID- 21179144
TI  - Keep it complex.

PMID- 21179151
TI  - Economic growth: a gross measure.

PMID- 21179152
TI  - Misreporting: hippo stories off-target.

PMID- 21179153
TI  - Brazil's renewable energy success.

PMID- 21179154
TI  - No crisis in supply of peer reviewers.

PMID- 21179155
TI  - Brian Marsden (1937-2010).

PMID- 21179157
TI  - Quantum technology: Electrons spin in the field.

PMID- 21179156
TI  - Human origins: Shadows of early migrations.

PMID- 21179158
TI  - Structural biology: Proteins in dynamic equilibrium.

PMID- 21179159
TI  - Behavioural neuroscience: A gene for impulsivity.

PMID- 21179160
TI  - Drug discovery: Reader's block.

PMID- 21179161
TI  - Genetic history of an archaic hominin group from Denisova Cave in Siberia.
AB  - Using DNA extracted from a finger bone found in Denisova Cave in southern
      Siberia, we have sequenced the genome of an archaic hominin to about 1.9-fold
      coverage. This individual is from a group that shares a common origin with
      Neanderthals. This population was not involved in the putative gene flow from
      Neanderthals into Eurasians; however, the data suggest that it contributed 4-6%
      of its genetic material to the genomes of present-day Melanesians. We designate
      this hominin population 'Denisovans' and suggest that it may have been widespread
      in Asia during the Late Pleistocene epoch. A tooth found in Denisova Cave carries
      a mitochondrial genome highly similar to that of the finger bone. This tooth
      shares no derived morphological features with Neanderthals or modern humans,
      further indicating that Denisovans have an evolutionary history distinct from
      Neanderthals and modern humans.

PMID- 21179162
TI  - A population-specific HTR2B stop codon predisposes to severe impulsivity.
AB  - Impulsivity, describing action without foresight, is an important feature of
      several psychiatric diseases, suicidality and violent behaviour. The complex
      origins of impulsivity hinder identification of the genes influencing it and the
      diseases with which it is associated. Here we perform exon-focused sequencing of
      impulsive individuals in a founder population, targeting fourteen genes belonging
      to the serotonin and dopamine domain. A stop codon in HTR2B was identified that
      is common (minor allele frequency > 1%) but exclusive to Finnish people.
      Expression of the gene in the human brain was assessed, as well as the molecular
      functionality of the stop codon, which was associated with psychiatric diseases
      marked by impulsivity in both population and family-based analyses. Knockout of
      Htr2b increased impulsive behaviours in mice, indicative of predictive validity.
      Our study shows the potential for identifying and tracing effects of rare alleles
      in complex behavioural phenotypes using founder populations, and indicates a role
      for HTR2B in impulsivity.

PMID- 21179164
TI  - Spin-orbit qubit in a semiconductor nanowire.
AB  - Motion of electrons can influence their spins through a fundamental effect called
      spin-orbit interaction. This interaction provides a way to control spins
      electrically and thus lies at the foundation of spintronics. Even at the level of
      single electrons, the spin-orbit interaction has proven promising for coherent
      spin rotations. Here we implement a spin-orbit quantum bit (qubit) in an indium
      arsenide nanowire, where the spin-orbit interaction is so strong that spin and
      motion can no longer be separated. In this regime, we realize fast qubit
      rotations and universal single-qubit control using only electric fields; the
      qubits are hosted in single-electron quantum dots that are individually
      addressable. We enhance coherence by dynamically decoupling the qubits from the
      environment. Nanowires offer various advantages for quantum computing: they can
      serve as one-dimensional templates for scalable qubit registers, and it is
      possible to vary the material even during wire growth. Such flexibility can be
      used to design wires with suppressed decoherence and to push semiconductor qubit
      fidelities towards error correction levels. Furthermore, electrical dots can be
      integrated with optical dots in p-n junction nanowires. The coherence times
      achieved here are sufficient for the conversion of an electronic qubit into a
      photon, which can serve as a flying qubit for long-distance quantum
      communication.

PMID- 21179163
TI  - Driving the cell cycle with a minimal CDK control network.
AB  - Control of eukaryotic cell proliferation involves an extended regulatory network,
      the complexity of which has made it difficult to understand the basic principles
      of the cell cycle. To investigate the core engine of the mitotic cycle we have
      generated a minimal control network in fission yeast that efficiently sustains
      cellular reproduction. Here we demonstrate that orderly progression through the
      major events of the cell cycle can be driven by oscillation of an engineered
      monomolecular cyclin-dependent protein kinase (CDK) module lacking much of the
      canonical regulation. We show further that the CDK oscillator acts as the primary
      organizer of the cell cycle, imposing timing and directionality to a system of
      two CDK activity thresholds that define independent cell cycle phases. We propose
      that this simple core architecture forms the basic control of the eukaryotic cell
      cycle.

PMID- 21179165
TI  - Mantle superplasticity and its self-made demise.
AB  - The unusual capability of solid crystalline materials to deform plastically,
      known as superplasticity, has been found in metals and even in ceramics. Such
      superplastic behaviour has been speculated for decades to take place in
      geological materials, ranging from surface ice sheets to the Earth's lower
      mantle. In materials science, superplasticity is confirmed when the material
      deforms with large tensile strain without failure; however, no experimental
      studies have yet shown this characteristic in geomaterials. Here we show that
      polycrystalline forsterite + periclase (9:1) and forsterite + enstatite +
      diopside (7:2.5:0.5), which are good analogues for Earth's mantle, undergo
      homogeneous elongation of up to 500 per cent under subsolidus conditions. Such
      superplastic deformation is accompanied by strain hardening, which is well
      explained by the grain size sensitivity of superplasticity and grain growth under
      grain switching conditions (that is, grain boundary sliding); grain boundary
      sliding is the main deformation mechanism for superplasticity. We apply the
      observed strain-grain size-viscosity relationship to portions of the mantle where
      superplasticity has been presumed to take place, such as localized shear zones in
      the upper mantle and within subducting slabs penetrating into the transition zone
      and lower mantle after a phase transformation. Calculations show that
      superplastic flow in the mantle is inevitably accompanied by significant grain
      growth that can bring fine grained (<=1 MUm) rocks to coarse-grained (1-10 mm)
      aggregates, resulting in increasing mantle viscosity and finally termination of
      superplastic flow.

PMID- 21179166
TI  - mTORC1 controls fasting-induced ketogenesis and its modulation by ageing.
AB  - The multi-component mechanistic target of rapamycin complex 1 (mTORC1) kinase is
      the central node of a mammalian pathway that coordinates cell growth with the
      availability of nutrients, energy and growth factors. Progress has been made in
      the identification of mTORC1 pathway components and in understanding their
      functions in cells, but there is relatively little known about the role of the
      pathway in vivo. Specifically, we have little knowledge regarding the role mTOCR1
      has in liver physiology. In fasted animals, the liver performs numerous functions
      that maintain whole-body homeostasis, including the production of ketone bodies
      for peripheral tissues to use as energy sources. Here we show that mTORC1
      controls ketogenesis in mice in response to fasting. We find that liver-specific
      loss of TSC1 (tuberous sclerosis 1), an mTORC1 inhibitor, leads to a fasting
      resistant increase in liver size, and to a pronounced defect in ketone body
      production and ketogenic gene expression on fasting. The loss of raptor
      (regulatory associated protein of mTOR, complex 1) an essential mTORC1 component,
      has the opposite effects. In addition, we find that the inhibition of mTORC1 is
      required for the fasting-induced activation of PPARalpha (peroxisome proliferator
      activated receptor alpha), the master transcriptional activator of ketogenic
      genes, and that suppression of NCoR1 (nuclear receptor co-repressor 1), a co
      repressor of PPARalpha, reactivates ketogenesis in cells and livers with
      hyperactive mTORC1 signalling. Like livers with activated mTORC1, livers from
      aged mice have a defect in ketogenesis, which correlates with an increase in
      mTORC1 signalling. Moreover, we show that the suppressive effects of mTORC1
      activation and ageing on PPARalpha activity and ketone production are not
      additive, and that mTORC1 inhibition is sufficient to prevent the ageing-induced
      defect in ketogenesis. Thus, our findings reveal that mTORC1 is a key regulator
      of PPARalpha function and hepatic ketogenesis and suggest a role for mTORC1
      activity in promoting the ageing of the liver.

PMID- 21179167
TI  - The histone variant macroH2A suppresses melanoma progression through regulation
      of CDK8.
AB  - Cancer is a disease consisting of both genetic and epigenetic changes. Although
      increasing evidence demonstrates that tumour progression entails chromatin
      mediated changes such as DNA methylation, the role of histone variants in cancer
      initiation and progression currently remains unclear. Histone variants replace
      conventional histones within the nucleosome and confer unique biological
      functions to chromatin. Here we report that the histone variant macroH2A (mH2A)
      suppresses tumour progression of malignant melanoma. Loss of mH2A isoforms,
      histone variants generally associated with condensed chromatin and fine-tuning of
      developmental gene expression programs, is positively correlated with increasing
      malignant phenotype of melanoma cells in culture and human tissue samples.
      Knockdown of mH2A isoforms in melanoma cells of low malignancy results in
      significantly increased proliferation and migration in vitro and growth and
      metastasis in vivo. Restored expression of mH2A isoforms rescues these malignant
      phenotypes in vitro and in vivo. We demonstrate that the tumour-promoting
      function of mH2A loss is mediated, at least in part, through direct
      transcriptional upregulation of CDK8. Suppression of CDK8, a colorectal cancer
      oncogene, inhibits proliferation of melanoma cells, and knockdown of CDK8 in
      cells depleted of mH2A suppresses the proliferative advantage induced by mH2A
      loss. Moreover, a significant inverse correlation between mH2A and CDK8
      expression levels exists in melanoma patient samples. Taken together, our results
      demonstrate that mH2A is a critical component of chromatin that suppresses the
      development of malignant melanoma, a highly intractable cutaneous neoplasm.

PMID- 21179168
TI  - S-glutathionylation uncouples eNOS and regulates its cellular and vascular
      function.
AB  - Endothelial nitric oxide synthase (eNOS) is critical in the regulation of
      vascular function, and can generate both nitric oxide (NO) and superoxide (O(2)(*
      )), which are key mediators of cellular signalling. In the presence of
      Ca(2+)/calmodulin, eNOS produces NO, endothelial-derived relaxing factor, from l
      arginine (l-Arg) by means of electron transfer from NADPH through a flavin
      containing reductase domain to oxygen bound at the haem of an oxygenase domain,
      which also contains binding sites for tetrahydrobiopterin (BH(4)) and l-Arg. In
      the absence of BH(4), NO synthesis is abrogated and instead O(2)(*-) is
      generated. While NOS dysfunction occurs in diseases with redox stress, BH(4)
      repletion only partly restores NOS activity and NOS-dependent vasodilation. This
      suggests that there is an as yet unidentified redox-regulated mechanism
      controlling NOS function. Protein thiols can undergo S-glutathionylation, a
      reversible protein modification involved in cellular signalling and adaptation.
      Under oxidative stress, S-glutathionylation occurs through thiol-disulphide
      exchange with oxidized glutathione or reaction of oxidant-induced protein thiyl
      radicals with reduced glutathione. Cysteine residues are critical for the
      maintenance of eNOS function; we therefore speculated that oxidative stress could
      alter eNOS activity through S-glutathionylation. Here we show that S
      glutathionylation of eNOS reversibly decreases NOS activity with an increase in
      O(2)(*-) generation primarily from the reductase, in which two highly conserved
      cysteine residues are identified as sites of S-glutathionylation and found to be
      critical for redox-regulation of eNOS function. We show that eNOS S
      glutathionylation in endothelial cells, with loss of NO and gain of O(2)(*-)
      generation, is associated with impaired endothelium-dependent vasodilation. In
      hypertensive vessels, eNOS S-glutathionylation is increased with impaired
      endothelium-dependent vasodilation that is restored by thiol-specific reducing
      agents, which reverse this S-glutathionylation. Thus, S-glutathionylation of eNOS
      is a pivotal switch providing redox regulation of cellular signalling,
      endothelial function and vascular tone.

PMID- 21179169
TI  - Transcriptional activation of polycomb-repressed genes by ZRF1.
AB  - Covalent modification of histones is fundamental in orchestrating chromatin
      dynamics and transcription. One example of such an epigenetic mark is the mono
      ubiquitination of histones, which mainly occurs at histone H2A and H2B.
      Ubiquitination of histone H2A has been implicated in polycomb-mediated
      transcriptional silencing. However, the precise role of the ubiquitin mark during
      silencing is still elusive. Here we show in human cell lines that ZRF1 (zuotin
      related factor 1) is specifically recruited to histone H2A when it is
      ubiquitinated at Lys 119 by means of a novel ubiquitin-interacting domain that is
      located in the evolutionarily conserved zuotin domain. At the onset of
      differentiation, ZRF1 specifically displaces polycomb-repressive complex 1 (PRC1)
      from chromatin and facilitates transcriptional activation. A genome-wide mapping
      of ZRF1, RING1B and H2A-ubiquitin targets revealed its involvement in the
      regulation of a large set of polycomb target genes, emphasizing the key role ZRF1
      has in cell fate decisions. We provide here a model of the molecular mechanism of
      switching polycomb-repressed genes to an active state.

PMID- 21179170
TI  - Neurotransmitter/sodium symporter orthologue LeuT has a single high-affinity
      substrate site.
AB  - Neurotransmitter/sodium symporters (NSSs) couple the uptake of neurotransmitter
      with one or more sodium ions, removing neurotransmitter from the synaptic cleft.
      NSSs are essential to the function of chemical synapses, are associated with
      multiple neurological diseases and disorders, and are the targets of therapeutic
      and illicit drugs. LeuT, a prokaryotic orthologue of the NSS family, is a model
      transporter for understanding the relationships between molecular mechanism and
      atomic structure in a broad range of sodium-dependent and sodium-independent
      secondary transporters. At present there is a controversy over whether there are
      one or two high-affinity substrate binding sites in LeuT. The first-reported
      crystal structure of LeuT, together with subsequent functional and structural
      studies, provided direct evidence for a single, high-affinity, centrally located
      substrate-binding site, defined as the S1 site. Recent binding, flux and
      molecular simulation studies, however, have been interpreted in terms of a model
      where there are two high-affinity binding sites: the central, S1, site and a
      second, the S2 site, located within the extracellular vestibule. Furthermore, it
      was proposed that the S1 and S2 sites are allosterically coupled such that
      occupancy of the S2 site is required for the cytoplasmic release of substrate
      from the S1 site. Here we address this controversy by performing direct
      measurement of substrate binding to wild-type LeuT and to S2 site mutants using
      isothermal titration calorimetry, equilibrium dialysis and scintillation
      proximity assays. In addition, we perform uptake experiments to determine whether
      the proposed allosteric coupling between the putative S2 site and the S1 site
      manifests itself in the kinetics of substrate flux. We conclude that LeuT
      harbours a single, centrally located, high-affinity substrate-binding site and
      that transport is well described by a simple, single-substrate kinetic mechanism.

PMID- 21179172
TI  - Construction of a novel expression cassette for increasing transgene expression
      in vivo in endothelial cells of large blood vessels.
AB  - The success of gene therapy hinges on achievement of adequate transgene
      expression. To ensure high transgene expression, many gene-therapy vectors
      include highly active virus-derived transcriptional elements. Other vectors
      include tissue-specific eukaryotic transcriptional elements, intended to limit
      transgene expression to specific cell types, avoid toxicity and prevent immune
      responses. Unfortunately, tissue specificity is often accompanied by lower
      transgene expression. Here, we use eukaryotic (murine) transcriptional elements
      and a virus-derived posttranscriptional element to build cassettes designed to
      express a potentially therapeutic gene (interleukin (IL)-10) in large-vessel
      endothelial cells (ECs) at levels as high as obtained with the cytomegalovirus
      (CMV) immediate early promoter, while retaining EC specificity. The cassettes
      were tested by incorporation into helper-dependent adenoviral vectors, and
      transduction into bovine aortic EC in vitro and rabbit carotid EC in vivo. The
      murine endothelin-1 promoter showed EC specificity, but expressed only 3% as much
      IL-10 mRNA as CMV. Inclusion of precisely four copies of an EC-specific enhancer
      and a posttranscriptional regulatory element increased IL-10 expression to a
      level at or above the CMV promoter in vivo, while retaining--and possibly
      enhancing--EC specificity, as measured in vitro. The cassette reported here will
      likely be useful for maximizing transgene expression in large-vessel EC, while
      minimizing systemic effects.

PMID- 21179173
TI  - Down-modulation of cancer targets using locked nucleic acid (LNA)-based antisense
      oligonucleotides without transfection.
AB  - Usually, small interfering RNAs and most antisense molecules need mechanical or
      chemical delivery methods to down-modulate the targeted mRNA. However, these
      delivery approaches complicate the interpretations of biological consequences. We
      show that locked nucleic acid (LNA)-based antisense oligonucleotides (LNA-ONs)
      readily down-modulate genes of interest in multiple cell lines without any
      delivery means. The down-modulation of genes was quick, robust, long-lasting and
      specific followed by potent down-modulation of protein. The efficiency of the
      effect varied among the 30 tumor cell lines investigated. The most robust effects
      were found in those cells where nuclear localization of the LNA-ON was clearly
      observed. Importantly, without using any delivery agent, we demonstrated that
      HER3 mRNA and protein could be efficiently down-modulated in cells and a tumor
      xenograft model. These data provide a simple and efficient approach to identify
      potential drug targets and animal models. Further elucidation of the mechanism of
      cellular uptake and trafficking of LNA-ONs may enhance not only the therapeutic
      values of this platform but also antisense molecules in general.

PMID- 21179174
TI  - Immunoresponse against the transgene limits hematopoietic engraftment of mice
      transplanted in utero with virally transduced fetal liver.
AB  - In utero cell and gene therapies constitute alternative strategies to the
      postnatal treatment of inherited diseases. Fetal hematopoietic progenitors could
      be a potential source of donor cells for these strategies. In this study,
      hematopoietic lineage-negative fetal liver cells from 14.5-day-old fetuses were
      transduced under different cytokine and culture combinations using a lentiviral
      vector expressing the enhanced green fluorescent protein (EGFP). When cells were
      transduced for 6 h in the presence of mSCF, hTPO and FLT3-L in retronectin-coated
      dishes at a multiplicity of infection of 10 transduction units/cell, up to 70% of
      granulo-macrophage colony-forming cells expressed the EGFP reporter gene. In
      utero transplantation experiments revealed that conditions leading to high
      transduction efficiencies were associated with poor engraftments of syngeneic
      recipients. Significantly, this effect was associated with the detection of a
      humoral and cellular immunoresponse against the transgenic protein. Moreover, the
      humoral response against EGFP was detected not only in in utero transplanted
      recipients but also in the operated mothers, suggesting the maternal origin of
      the anti-EGFP immunoresponse. These observations reinforce the necessity of
      carefully studying the potential immunoresponses in future prenatal gene therapy
      protocols.

PMID- 21179175
TI  - Evaluation of delivery conditions for cutaneous plasmid electrotransfer using a
      multielectrode array.
AB  - Electroporation (EP) is a simple in vivo method to deliver normally impermeable
      molecules, such as plasmid DNA, to a variety of tissues. Delivery of plasmid DNA
      by EP to a large surface area is not practical because the distance between the
      electrode pairs, and therefore the applied voltage, must be increased to
      effectively permeabilize the cell membrane. The design of the multielectrode
      array (MEA) incorporates multiple electrode pairs at a fixed distance to allow
      for delivery of plasmid DNA to the skin, potentially reducing the sensation
      associated with in vivo EP. In this report, we evaluate the effects of field
      strength and pulse width on transgene expression and duration using a plasmid
      encoding the luciferase reporter gene delivered by intradermal injection in a
      guinea pig model followed by EP with the MEA. As expected, the level of
      luciferase expression increased with the magnitude and duration of the voltage
      applied. In addition to adjusting transgene expression levels by altering
      fielding strength, levels could also be controlled by adjusting the plasmid dose.
      Our results indicate that the design of the MEA is a viable option for cutaneous
      plasmid DNA delivery by in vivo EP to a large surface area.

PMID- 21179177
TI  - An old disease, a new disease or something in between: evidence from China.

PMID- 21179176
TI  - Inside the human cancer tyrosine phosphatome.
AB  - Members of the protein tyrosine phosphatase (Ptp) family dephosphorylate target
      proteins and counter the activities of protein tyrosine kinases that are involved
      in cellular phosphorylation and signalling. As such, certain PTPs might be tumour
      suppressors. Indeed, PTPs play an important part in the inhibition or control of
      growth, but accumulating evidence indicates that some PTPs may exert oncogenic
      functions. Recent large-scale genetic analyses of various human tumours have
      highlighted the relevance of PTPs either as putative tumour suppressors or as
      candidate oncoproteins. Progress in understanding the regulation and function of
      PTPs has provided insights into which PTPs might be potential therapeutic targets
      in human cancer.

PMID- 21179178
TI  - Cancer is an ancient disease: the case for better palaeoepidemiological and
      molecular studies.

PMID- 21179180
TI  - Choroidal neovascularization secondary to congenital toxoplasmosis in an infant.

PMID- 21179181
TI  - Anterior lens capsule rupture following non-penetrating ocular injury in elderly
      patients.

PMID- 21179182
TI  - Regeneration of cornea long after amniotic membrane grafting to treat corneal
      perforation.

PMID- 21179183
TI  - Autopsy causes of death in HIV-positive individuals in sub-Saharan Africa and
      correlation with clinical diagnoses.
AB  - Despite the persistently high HIV-related mortality in sub-Saharan Africa,
      limited information on the causes of death is available. Pathological autopsies
      are the gold standard to establish causes of death. In this review we describe
      the autopsy series performed among HIV-infected individuals in sub-Saharan Africa
      over the last two decades. We identified nine complete and 11 partial or
      minimally invasive autopsy series. Complete autopsies were performed in 593 HIV
      positive adults and 177 HIV-positive children. Postmortem diagnoses were mainly
      infectious diseases. Tuberculosis was the most frequent, present in 21-54% of HIV
      positive adults and was considered the cause of death in 32-45%. Overall,
      pulmonary infections accounted for approximately 66% of pathology and central
      nervous system infections for approximately 20%. A high discordance between
      clinical and postmortem diagnoses was observed. This review emphasizes the need
      for reliable information on causes of death in order to improve HIV patient care,
      guide further research, and inform health policy.

PMID- 21179184
TI  - Dried blood spots for HIV-1 drug resistance and viral load testing: A review of
      current knowledge and WHO efforts for global HIV drug resistance surveillance.
AB  - HIV-1 drug resistance genotyping is an essential component of the World Health
      Organization global HIV Drug Resistance (HIVDR) prevention and assessment
      strategy. Plasma is considered to be the most appropriate specimen type for HIV-1
      drug resistance genotyping. However, use of plasma may not be feasible in rural,
      remote areas in resource-limited settings since its preparation and storage
      requires personnel and laboratory infrastructure that is often lacking. An
      alternative specimen type for HIVDR genotyping is dried blood spots (DBS). DBS
      can be made from blood drawn for routine clinical or surveillance purposes
      without special laboratory processing. The filter paper used is relatively
      inexpensive, easily obtained and stored, and although procedures for making DBS
      must be followed precisely, the training required is less intensive than that
      required for plasma separation. HIV nucleic acids are generally stable over long
      periods of time and freezing is not required unless storage over two weeks is
      planned. In addition, DBS are more easily transported than plasma because they
      can be shipped as non-hazardous materials using regular mail or courier services.
      Many studies have reported the successful genotyping of HIV-1 from DBS and some
      have shown a high genotypic concordance with plasma genotypes despite potential
      DNA interferences. During the past few years DBS have started to be widely used
      for HIV-1 drug resistance testing, and an increased number of reports from
      resource-limited areas have indicated DBS as the preferred specimen type for
      transmitted HIV-1 drug resistance surveillance where plasma collection is not
      feasible. The World Health Organization has brought together a group of experts
      (WHO HIVResNet DBS working group) to review current data on DBS preparation,
      storage, and transport conditions, and provide a reference protocol, which is
      also summarized in this article.

PMID- 21179185
TI  - HIV vaccine efficacy trials: A brief history, and options for going forward.
AB  - HIV vaccine research has recently produced a number of efficacy results, in
      addition to some promising preclinical developments. Some of these have been
      surprising, leading to parallel calls for a better understanding of HIV
      pathogenesis and immunity, while accelerating the number of candidates that can
      be tested empirically in clinical trials. In this review, we describe the
      development of three HIV vaccine efficacy trials to date, and highlight some of
      the possible avenues available for the field of biomedical HIV prevention to
      proceed.

PMID- 21179186
TI  - HIV infection and aging.
AB  - The median age of HIV-infected patients is increasing all over the world. Age has
      a significant impact on some aspects of HIV-infection when compared to younger
      patients. Diagnostic delay and late presentation are more frequent in older
      patients because some of the initial symptoms are masked by age and because older
      people are not considered to be a risk group for HIV infection. Despite the
      clinical, immunological, and virologic benefits of HAART, most studies suggest
      that older patients have a poorer immunological and clinical response to HAART
      than younger patients, despite a similar virologic response. Other problems
      include the frequent presence of comorbid conditions and medications that can
      affect the efficacy and safety of HAART as well as its pharmacokinetics and
      pharmacodynamics. Because no guidelines recommend a specific HAART regimen for
      older people, specific clinical trials and pharmacological studies should be
      designed to optimize HAART in these patients.

PMID- 21179187
TI  - Management of metabolic complications and cardiovascular risk in HIV-infected
      patients.
AB  - As result of the great benefit of HAART, AIDS-related deaths have dramatically
      declined during the last decade in HIV-infected individuals. However, mortality
      due to non-AIDS conditions and particularly cardiovascular events seems to be on
      the rise in this population. Metabolic complications and other conditions
      responsible for increased cardiovascular risk are common in HIV persons.
      Moreover, antiretroviral medications and HIV itself might play a role in further
      increasing cardiovascular risk. As the HIV population is aging, a growing impact
      of cardiovascular events on survival can be expected. Therefore, early diagnosis
      and treatment of predisposing cardiovascular risk factors is warranted in this
      population. In this way, all HIV-infected individuals should be evaluated
      regularly for lipid abnormalities, hyperglycemia, arterial hypertension,
      overweight, renal disease, and smoking. The individual's absolute risk for
      coronary heart disease must be defined, and comprehensive therapeutic measures
      should be undertaken in order to minimize future complications in subjects with
      significant cardiovascular risk. Lifestyle habits must be encouraged, including
      healthy diet and exercise. Switches in antiretroviral regimens using metabolic
      friendly agents should also be considered for managing mild metabolic
      abnormalities in lipids and glucose, as long as suppression of viral replication
      is not compromised. The management of overt lipid disorders, diabetes, and
      hypertension basically must follow the guidelines applied to the general
      population and specific drugs administered, taking into account the potential for
      drug interactions with antiretroviral agents. In summary, efforts for reducing
      the increased cardiovascular risk characteristically seen in HIV-infected
      individuals are warranted, and preventable factors, including adequate management
      of metabolic abnormalities and hypertension, along with promotion of lifestyle
      habits and smoke cessation, should no longer be neglected.

PMID- 21179189
TI  - Biodiversity trends along the western European margin.

PMID- 21179188
TI  - Zebrafish numb and numblike are involved in primitive erythrocyte
      differentiation.
AB  - BACKGROUND: Notch signaling is an evolutionarily conserved regulatory circuitry
      implicated in cell fate determination in various developmental processes
      including hematopoietic stem cell self-renewal and differentiation of blood
      lineages. Known endogenous inhibitors of Notch activity are Numb-Nb and Numblike
      Nbl, which play partially redundant functions in specifying and maintaining
      neuronal differentiation. Nb and Nbl are expressed in most tissues including
      embryonic and adult hematopoietic tissues in mice and humans, suggesting possible
      roles for these proteins in hematopoiesis. METHODOLOGY AND PRINCIPAL FINDINGS: We
      employed zebrafish to investigate the possible functional role of Numb and
      Numblike during hematopoiesis, as this system allows a detailed analysis even in
      embryos with severe defects that would be lethal in other organisms. Here we
      describe that nb/nbl knockdown results in severe reduction or absence of
      embryonic erythrocytes in zebrafish. Interestingly, nb/nbl knocked-down embryos
      present severe downregulation of the erythroid transcription factor gata1. This
      results in erythroblasts which fail to mature and undergo apoptosis. Our results
      indicate that Notch activity is increased in embryos injected with nb/nbl
      morpholino, and we show that inhibition of Notch activation can partially rescue
      the hematopoietic phenotype. CONCLUSIONS AND SIGNIFICANCE: Our results provide
      the first in vivo evidence of an involvement of Numb and Numblike in zebrafish
      erythroid differentiation during primitive hematopoiesis. Furthermore, we found
      that, at least in part, the nb/nbl morphant phenotype is due to enhanced Notch
      activation within hematopoietic districts, which in turn results in primitive
      erythroid differentiation defects.

PMID- 21179191
TI  - An in situ, individual-based approach to quantify connectivity of marine fish:
      ontogenetic movements and residency of lingcod.
AB  - As modern fishery assessments change in an effort to be more accurate and
      encompass the range of potential ecosystem interactions, critical information on
      the ecology of species including life history, intra and inter-specific
      competitive interactions and habitat requirements must be added to the standard
      fishery-dependent and independent data sets. One species whose movements and
      habitat associations greatly affects exploitation patterns is lingcod, Ophiodon
      elongatus, which support an economically important fishery along the coastal
      waters of the Pacific Coast of North America. High site fidelity and limited
      movements within nearshore areas are hypothesized to have resulted in high
      catchability, a major factor that has contributed to overfished stocks. Thus,
      assessing the level of movement and connectivity among lingcod subpopulations
      inhabiting nearshore habitats is a prerequisite to determining the condition of
      lingcod stocks. We used the Pacific Ocean Shelf Tracking (POST) Project acoustic
      receiver array in Alaska's Prince William Sound to monitor movements and
      residency of 21 acoustic-tagged lingcod for up to 16 months. Eight of sixteen
      lingcod (50%) initially aged at 2.5- to 3.5- years-old dispersed from their tag
      site. Dispersal was highly seasonal, occurring in two, five-week periods from mid
      December through January and from mid-April through May. Dispersal in winter may
      be related to sexually immature lingcod or newly-mature male lingcod being
      displaced by territorial males. Spring dispersal may be indicative of the onset
      of migratory behavior where lingcod move out into Prince William Sound and
      possibly the offshore waters of the Gulf of Alaska. Our results reveal a pattern
      of ontogenetic dispersal as lingcod approach 4-years-old and exceed 50 cm total
      length. The large proportion of tagged fish migrating out of Port Gravina, their
      tagging site, reflects a high level of connectivity among Prince William Sound
      subpopulations. Our results also support the hypotheses that these subpopulations
      may be highly susceptible to overfishing because most fish show long residence
      times.

PMID- 21179190
TI  - Accurate protein structure annotation through competitive diffusion of enzymatic
      functions over a network of local evolutionary similarities.
AB  - High-throughput Structural Genomics yields many new protein structures without
      known molecular function. This study aims to uncover these missing annotations by
      globally comparing select functional residues across the structural proteome.
      First, Evolutionary Trace Annotation, or ETA, identifies which proteins have
      local evolutionary and structural features in common; next, these proteins are
      linked together into a proteomic network of ETA similarities; then, starting from
      proteins with known functions, competing functional labels diffuse link-by-link
      over the entire network. Every node is thus assigned a likelihood z-score for
      every function, and the most significant one at each node wins and defines its
      annotation. In high-throughput controls, this competitive diffusion process
      recovered enzyme activity annotations with 99% and 97% accuracy at half-coverage
      for the third and fourth Enzyme Commission (EC) levels, respectively. This
      corresponds to false positive rates 4-fold lower than nearest-neighbor and 5-fold
      lower than sequence-based annotations. In practice, experimental validation of
      the predicted carboxylesterase activity in a protein from Staphylococcus aureus
      illustrated the effectiveness of this approach in the context of an increasingly
      drug-resistant microbe. This study further links molecular function to a small
      number of evolutionarily important residues recognizable by Evolutionary Tracing
      and it points to the specificity and sensitivity of functional annotation by
      competitive global network diffusion. A web server is at
      http://mammoth.bcm.tmc.edu/networks.

PMID- 21179192
TI  - Membrane Permeabilization by Oligomeric alpha-Synuclein: In Search of the
      Mechanism.
AB  - BACKGROUND: The question of how the aggregation of the neuronal protein alpha
      synuclein contributes to neuronal toxicity in Parkinson's disease has been the
      subject of intensive research over the past decade. Recently, attention has
      shifted from the amyloid fibrils to soluble oligomeric intermediates in the alpha
      synuclein aggregation process. These oligomers are hypothesized to be cytotoxic
      and to permeabilize cellular membranes, possibly by forming pore-like complexes
      in the bilayer. Although the subject of alpha-synuclein oligomer-membrane
      interactions has attracted much attention, there is only limited evidence that
      supports the pore formation by alpha-synuclein oligomers. In addition the
      existing data are contradictory. METHODOLOGY/PRINCIPAL FINDINGS: Here we have
      studied the mechanism of lipid bilayer disruption by a well-characterized alpha
      synuclein oligomer species in detail using a number of in vitro bilayer systems
      and assays. Dye efflux from vesicles induced by oligomeric alpha-synuclein was
      found to be a fast all-or-none process. Individual vesicles swiftly lose their
      contents but overall vesicle morphology remains unaltered. A newly developed
      assay based on a dextran-coupled dye showed that non-equilibrium processes
      dominate the disruption of the vesicles. The membrane is highly permeable to
      solute influx directly after oligomer addition, after which membrane integrity is
      partly restored. The permeabilization of the membrane is possibly related to the
      intrinsic instability of the bilayer. Vesicles composed of negatively charged
      lipids, which are generally used for measuring alpha-synuclein-lipid
      interactions, were unstable to protein adsorption in general.
      CONCLUSIONS/SIGNIFICANCE: The dye efflux from negatively charged vesicles upon
      addition of alpha-synuclein has been hypothesized to occur through the formation
      of oligomeric membrane pores. However, our results show that the dye efflux
      characteristics are consistent with bilayer defects caused by membrane
      instability. These data shed new insights into potential mechanisms of toxicity
      of oligomeric alpha-synuclein species.

PMID- 21179193
TI  - The management of Staphylococcus aureus bacteremia in the United Kingdom and
      Vietnam: a multi-centre evaluation.
AB  - BACKGROUND: Staphylococcus aureus bacteremia is a common and serious infection
      worldwide and although treatment guidelines exist, there is little consensus on
      optimal management. In this study we assessed the variation in management and
      adherence to treatment guidelines of S. aureus bacteremia. METHODOLOGY/PRINCIPAL
      FINDINGS: We prospectively recorded baseline clinical characteristics,
      management, and in-hospital outcome of all adults with S. aureus bacteremia
      treated consecutively over one year in eight centres in the United Kingdom, three
      in Vietnam and one in Nepal. 630 adults were treated for S. aureus bacteremia:
      549 in the UK (21% methicillin-resistant), 80 in Vietnam (19% methicillin
      resistant) and 1 in Nepal. In the UK, 41% had a removable infection focus (50%
      intravenous catheter-related), compared to 12% in Vietnam. Significantly
      (p<0.001) higher proportions of UK than Vietnamese patients had an echocardiogram
      (50% versus 28%), received more than 14 days antibiotic therapy (84% versus 44%),
      and received >50% of treatment with oral antibiotics alone (25% versus 4%). UK
      centres varied significantly (p<0.01) in the proportions given oral treatment
      alone for >50% of treatment (range 12-40%), in those treated for longer than 28
      days (range 13-54%), and in those given combination therapy (range 14-94%). 24%
      died during admission: older age, time in hospital before bacteremia, and an
      unidentified infection focus were independent predictors of in-hospital death
      (p<0.001). CONCLUSIONS/SIGNIFICANCE: The management of S. aureus bacteremia
      varies widely between the UK and Vietnam and between centres in the UK with
      little adherence to published guidelines. Controlled trials defining optimal
      therapy are urgently required.

PMID- 21179194
TI  - UEV-1 is an ubiquitin-conjugating enzyme variant that regulates glutamate
      receptor trafficking in C. elegans neurons.
AB  - The regulation of AMPA-type glutamate receptor (AMPAR) membrane trafficking is a
      key mechanism by which neurons regulate synaptic strength and plasticity. AMPAR
      trafficking is modulated through a combination of receptor phosphorylation,
      ubiquitination, endocytosis, and recycling, yet the factors that mediate these
      processes are just beginning to be uncovered. Here we identify the ubiquitin
      conjugating enzyme variant UEV-1 as a regulator of AMPAR trafficking in vivo. We
      identified mutations in uev-1 in a genetic screen for mutants with altered
      trafficking of the AMPAR subunit GLR-1 in C. elegans interneurons. Loss of uev-1
      activity results in the accumulation of GLR-1 in elongated accretions in neuron
      cell bodies and along the ventral cord neurites. Mutants also have a
      corresponding behavioral defect--a decrease in spontaneous reversals in
      locomotion--consistent with diminished GLR-1 function. The localization of other
      synaptic proteins in uev-1-mutant interneurons appears normal, indicating that
      the GLR-1 trafficking defects are not due to gross deficiencies in synapse
      formation or overall protein trafficking. We provide evidence that GLR-1
      accumulates at RAB-10-containing endosomes in uev-1 mutants, and that receptors
      arrive at these endosomes independent of clathrin-mediated endocytosis. UEV-1
      homologs in other species bind to the ubiquitin-conjugating enzyme Ubc13 to
      create K63-linked polyubiquitin chains on substrate proteins. We find that
      whereas UEV-1 can interact with C. elegans UBC-13, global levels of K63-linked
      ubiquitination throughout nematodes appear to be unaffected in uev-1 mutants,
      even though UEV-1 is broadly expressed in most tissues. Nevertheless, ubc-13
      mutants are similar in phenotype to uev-1 mutants, suggesting that the two
      proteins do work together to regulate GLR-1 trafficking. Our results suggest that
      UEV-1 could regulate a small subset of K63-linked ubiquitination events in
      nematodes, at least one of which is critical in regulating GLR-1 trafficking.

PMID- 21179195
TI  - Developing pulmonary vasculopathy in systemic sclerosis, detected with non
      invasive cardiopulmonary exercise testing.
AB  - BACKGROUND: Patients with systemic sclerosis (SSc) may develop exercise
      intolerance due to musculoskeletal involvement, restrictive lung disease, left
      ventricular dysfunction, or pulmonary vasculopathy (PV). The latter is
      particularly important since it may lead to lethal pulmonary arterial
      hypertension (PAH). We hypothesized that abnormalities during cardiopulmonary
      exercise testing (CPET) in patients with SSc can identify PV leading to overt
      PAH. METHODS: Thirty SSc patients from the Harbor-UCLA Rheumatology clinic, not
      clinically suspected of having significant pulmonary vascular disease, were
      referred for this prospective study. Resting pulmonary function and exercise gas
      exchange were assessed, including peakVO2, anaerobic threshold (AT), heart rate
      VO2 relationship (O2-pulse), exercise breathing reserve and parameters of
      ventilation-perfusion mismatching, as evidenced by elevated ventilatory
      equivalent for CO2 (VE/VCO2) and reduced end-tidal pCO2 (PETCO2) at the AT.
      RESULTS: Gas exchange patterns were abnormal in 16 pts with specific
      cardiopulmonary disease physiology: Eleven patients had findings consistent with
      PV, while five had findings consistent with left-ventricular dysfunction (LVD).
      Although both groups had low peak VO2 and AT, a higher VE/VCO2 at AT and
      decreasing PETCO2 during early exercise distinguished PV from LVD. CONCLUSIONS:
      Previously undiagnosed exercise impairments due to LVD or PV were common in our
      SSc patients. Cardiopulmonary exercise testing may help to differentiate and
      detect these disorders early in patients with SSc.

PMID- 21179196
TI  - Multisite phosphorylation provides an effective and flexible mechanism for switch
      like protein degradation.
AB  - Phosphorylation-triggered degradation is a common strategy for elimination of
      regulatory proteins in many important cell signaling processes. Interesting
      examples include cyclin-dependent kinase inhibitors such as p27 in human and Sic1
      in yeast, which play crucial roles during the G1/S transition in the cell cycle.
      In this work, we have modeled and analyzed the dynamics of multisite
      phosphorylation-triggered protein degradation systematically. Inspired by
      experimental observations on the Sic1 protein and a previous intriguing
      theoretical conjecture, we develop a model to examine in detail the degradation
      dynamics of a protein featuring multiple phosphorylation sites and a threshold
      site number for elimination in response to a kinase signal. Our model explains
      the role of multiple phosphorylation sites, compared to a single site, in the
      regulation of protein degradation. A single-site protein cannot convert a graded
      input of kinase increase to much sharper output, whereas multisite
      phosphorylation is capable of generating a highly switch-like temporal profile of
      the substrate protein with two characteristics: a temporal threshold and rapid
      decrease beyond the threshold. We introduce a measure termed temporal response
      coefficient to quantify the extent to which a response in the time domain is
      switch-like and further investigate how this property is determined by various
      factors including the kinase input, the total number of sites, the threshold site
      number for elimination, the order of phosphorylation, the kinetic parameters, and
      site preference. Some interesting and experimentally verifiable predictions
      include that the non-degradable fraction of the substrate protein exhibits a more
      switch-like temporal profile; a sequential system is more switch-like, while a
      random system has the advantage of increased robustness; all the parameters,
      including the total number of sites, the threshold site number for elimination
      and the kinetic parameters synergistically determine the exact extent to which
      the degradation profile is switch-like. Our results suggest design principles for
      protein degradation switches which might be a widespread mechanism for precise
      regulation of cellular processes such as cell cycle progression.

PMID- 21179197
TI  - The combined effects of amino acid substitutions and indels on the evolution of
      structure within protein families.
AB  - BACKGROUND: In the process of protein evolution, sequence variations within
      protein families can cause changes in protein structures and functions. However,
      structures tend to be more conserved than sequences and functions. This leads to
      an intriguing question: what is the evolutionary mechanism by which sequence
      variations produce structural changes? To investigate this question, we focused
      on the most common types of sequence variations: amino acid substitutions and
      insertions/deletions (indels). Here their combined effects on protein structure
      evolution within protein families are studied. RESULTS: Sequence-structure
      correlation analysis on 75 homologous structure families (from SCOP) that contain
      20 or more non-redundant structures shows that in most of these families there
      is, statistically, a bilinear correlation between the amount of substitutions and
      indels versus the degree of structure variations. Bilinear regression of percent
      sequence non-identity (PNI) and standardized number of gaps (SNG) versus RMSD was
      performed. The coefficients from the regression analysis could be used to
      estimate the structure changes caused by each unit of substitution (structural
      substitution sensitivity, SSS) and by each unit of indel (structural indel
      sensitivity, SIDS). An analysis on 52 families with high bilinear fitting
      multiple correlation coefficients and statistically significant regression
      coefficients showed that SSS is mainly constrained by disulfide bonds, which
      almost have no effects on SIDS. CONCLUSIONS: Structural changes in homologous
      protein families could be rationally explained by a bilinear model combining
      amino acid substitutions and indels. These results may further improve our
      understanding of the evolutionary mechanisms of protein structures.

PMID- 21179198
TI  - Purification and in situ immobilization of papain with aqueous two-phase system.
AB  - Papain was purified from spray-dried Carica papaya latex using aqueous two-phase
      system (ATPS). Then it was recovered from PEG phase by in situ immobilization or
      preparing cross-linked enzyme aggregates (CLEAs). The Plackett-Burman design and
      the central composite design (CCD) together with the response surface methodology
      (RSM) were used to optimize the APTS processes. The highly purified papain (96
      100%) was achieved under the optimized conditions: 40% (w/w) 15 mg/ml enzyme
      solution, 14.33-17.65% (w/w) PEG 6000, 14.27-14.42% (w/w) NaH2PO4/K2HPO4 and pH
      5.77-6.30 at 20 degrees C. An in situ enzyme immobilization approach, carried out
      by directly dispersing aminated supports and chitosan beads into the PEG phase,
      was investigated to recover papain, in which a high immobilization yield (>90%)
      and activity recovery (>40%) was obtained. Moreover, CLEAs were successfully used
      in recovering papain from PEG phase with a hydrolytic activity hundreds times
      higher than the carrier-bound immobilized papain.

PMID- 21179199
TI  - Effects of inhibition of interleukin-6 signalling on insulin sensitivity and
      lipoprotein (a) levels in human subjects with rheumatoid diseases.
AB  - BACKGROUND: Interleukin-6 (IL-6) is a pro-inflammatory cytokine that has been
      found to be increased in type 2 diabetic subjects. However, it still remains
      unclear if these elevated IL-6 levels are co-incidental or if this cytokine is
      causally related to the development of insulin resistance and type 2 diabetes in
      humans. Therefore, in the present study we examined insulin sensitivity, serum
      adipokine levels and lipid parameters in human subjects before and after
      treatment with the IL-6 receptor antibody Tocilizumab. METHODOLOGY/PRINCIPAL
      FINDINGS: 11 non-diabetic patients with rheumatoid disease were included in the
      study. HOMA-IR was calculated and serum levels for leptin, adiponectin,
      triglycerides, LDL-cholesterol, HDL-cholesterol and lipoprotein (a) (Lp (a)) were
      measured before as well as one and three months after Tocilizumab treatment. The
      HOMA index for insulin resistance decreased significantly. While leptin
      concentrations were not altered by inhibition of IL-6 signalling, adiponectin
      concentrations significantly increased. Thus the leptin to adiponectin ratio, a
      novel marker for insulin resistance, exhibited a significant decrease. Serum
      triglycerides, LDL-cholesterol and HDL-cholesterol tended to be increased whereas
      Lp (a) levels significantly decreased. CONCLUSIONS/SIGNIFICANCE: Inhibition of IL
      6 signalling improves insulin sensitivity in humans with immunological disease
      suggesting that elevated IL-6 levels in type 2 diabetic subjects might be
      causally involved in the pathogenesis of insulin resistance. Furthermore, our
      data indicate that inhibition of IL-6 signalling decreases Lp (a) serum levels,
      which might reduce the cardiovascular risk of human subjects.

PMID- 21179200
TI  - Genetic inactivation of Trpml3 does not lead to hearing and vestibular impairment
      in mice.
AB  - TRPML3, a member of the transient receptor potential (TRP) family, is an inwardly
      rectifying, non-selective Ca2+-permeable cation channel that is regulated by
      extracytosolic Na+ and H+ and can be activated by a variety of small molecules.
      The severe auditory and vestibular phenotype of the TRPML3(A419P) varitint
      waddler mutation made this protein particularly interesting for inner ear
      biology. To elucidate the physiological role of murine TRPML3, we conditionally
      inactivated Trpml3 in mice. Surprisingly, lack of functional TRPML3 did not lead
      to circling behavior, balance impairment or hearing loss.

PMID- 21179201
TI  - Safety and T cell modulating effects of high dose vitamin D3 supplementation in
      multiple sclerosis.
AB  - BACKGROUND: A poor vitamin D status has been associated with a high disease
      activity of multiple sclerosis (MS). Recently, we described associations between
      vitamin D status and peripheral T cell characteristics in relapsing remitting MS
      (RRMS) patients. In the present study, we studied the effects of high dose
      vitamin D3 supplementation on safety and T cell related outcome measures.
      METHODOLOGY/PRINCIPAL FINDINGS: Fifteen RRMS patients were supplemented with
      20,000 IU/d vitamin D3 for 12 weeks. Vitamin D and calcium metabolism were
      carefully monitored, and T cell characteristics were studied by flowcytometry.
      All patients finished the protocol without side-effects, hypercalcaemia, or
      hypercalciuria. The median vitamin D status increased from 50 nmol/L (31-175) at
      week 0 to 380 nmol/L (151-535) at week 12 (P<0.001). During the study, 1 patient
      experienced an exacerbation of MS and was censored from the T cell analysis. The
      proportions of (naive and memory) CD4+ Tregs remained unaffected. Although Treg
      suppressive function improved in several subjects, this effect was not
      significant in the total cohort (P=0.143). An increased proportion of IL-10+ CD4+
      T cells was found after supplementation (P=0.021). Additionally, a decrease of
      the ratio between IFN-gamma+ and IL-4+ CD4+ T cells was observed (P=0.035).
      CONCLUSION/SIGNIFICANCE: Twelve week supplementation of high dose vitamin D3 in
      RRMS patients was well tolerated and did not induce decompensation of calcium
      metabolism. The skewing towards an anti-inflammatory cytokine profile supports
      the evidence on vitamin D as an immune-modulator, and may be used as outcome
      measure for upcoming randomized placebo-controlled trials. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT00940719.

PMID- 21179202
TI  - Zinc downregulates HIF-1alpha and inhibits its activity in tumor cells in vitro
      and in vivo.
AB  - BACKGROUND: Hypoxia inducible factor-1alpha (HIF-1alpha) is responsible for the
      majority of HIF-1-induced gene expression changes under hypoxia and for the
      "angiogenic switch" during tumor progression. HIF-1alpha is often upregulated in
      tumors leading to more aggressive tumor growth and chemoresistance, therefore
      representing an important target for antitumor intervention. We previously
      reported that zinc downregulated HIF-1alpha levels. Here, we evaluated the
      molecular mechanisms of zinc-induced HIF-1alpha downregulation and whether zinc
      affected HIF-1alpha also in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Here we report
      that zinc downregulated HIF-1alpha protein levels in human prostate cancer and
      glioblastoma cells under hypoxia, whether induced or constitutive. Investigations
      into the molecular mechanisms showed that zinc induced HIF-1alpha proteasomal
      degradation that was prevented by treatment with proteasomal inhibitor MG132. HIF
      1alpha downregulation induced by zinc was ineffective in human RCC4 VHL-null
      renal carcinoma cell line; likewise, the HIF-1alphaP402/P564A mutant was
      resistant to zinc treatment. Similarly to HIF-1alpha, zinc downregulated also
      hypoxia-induced HIF-2alpha whereas the HIF-1beta subunit remained unchanged. Zinc
      inhibited HIF-1alpha recruitment onto VEGF promoter and the zinc-induced
      suppression of HIF-1-dependent activation of VEGF correlated with reduction of
      glioblastoma and prostate cancer cell invasiveness in vitro. Finally, zinc
      administration downregulated HIF-1alpha levels in vivo, by bioluminescence
      imaging, and suppressed intratumoral VEGF expression. CONCLUSIONS/SIGNIFICANCE:
      These findings, by demonstrating that zinc induces HIF-1alpha proteasomal
      degradation, indicate that zinc could be useful as an inhibitor of HIF-1alpha in
      human tumors to repress important pathways involved in tumor progression, such as
      those induced by VEGF, MDR1, and Bcl2 target genes, and hopefully potentiate the
      anticancer therapies.

PMID- 21179203
TI  - T tubules and surface membranes provide equally effective pathways of carbonic
      anhydrase-facilitated lactic acid transport in skeletal muscle.
AB  - We have studied lactic acid transport in the fast mouse extensor digitorum longus
      muscles (EDL) by intracellular and cell surface pH microelectrodes. The role of
      membrane-bound carbonic anhydrases (CA) of EDL in lactic acid transport was
      investigated by measuring lactate flux in muscles from wildtype, CAIV-, CAIX- and
      CAXIV-single ko, CAIV-CAXIV double ko and CAIV-CAIX-CAXIV-triple ko mice. This
      was complemented by immunocytochemical studies of the subcellular localization of
      CAIV, CAIX and CAXIV in mouse EDL. We find that CAXIV and CAIX single ko EDL
      exhibit markedly but not maximally reduced lactate fluxes, whereas triple ko and
      double ko EDL show maximal or near-maximal inhibition of CA-dependent lactate
      flux. Interpretation of the flux measurements in the light of the
      immunocytochemical results leads to the following conclusions. CAXIV, which is
      homogeneously distributed across the surface membrane of EDL fibers, facilitates
      lactic acid transport across this membrane. CAIX, which is associated only with T
      tubular membranes, facilitates lactic acid transport across the T tubule
      membrane. The removal of lactic acid from the lumen of T tubuli towards the
      interstitial space involves a CO2-HCO3- diffusional shuttle that is maintained
      cooperatively by CAIX within the T tubule and, besides CAXIV, by the CAIV, which
      is strategically located at the opening of the T tubules. The data suggest that
      about half the CA-dependent muscular lactate flux occurs across the surface
      membrane, while the other half occurs across the membranes of the T tubuli.

PMID- 21179204
TI  - c-kitpos GATA-4 high rat cardiac stem cells foster adult cardiomyocyte survival
      through IGF-1 paracrine signalling.
AB  - BACKGROUND: Resident c-kit positive (c-kitpos) cardiac stem cells (CSCs) could be
      considered the most appropriate cell type for myocardial regeneration therapies.
      However, much is still unknown regarding their biological properties and
      potential. METHODOLOGY/PRINCIPAL FINDINGS: We produced clones of high and low
      expressing GATA-4 CSCs from long-term bulk-cultured c-kitpos CSCs isolated from
      adult rat hearts. When c-kitpos GATA-4 high expressing clonal CSCs (cCSCs) were
      co-cultured with adult rat ventricular cardiomyocytes, we observed increased
      survival and contractility of the cardiomyocytes, compared to cardiomyocytes
      cultured alone, co-cultured with fibroblasts or c-kitpos GATA-4 low expressing
      cCSCs. When analysed by ELISA, the concentration of IGF-1 was significantly
      increased in the c-kitpos GATA-4 high cCSC/cardiomyocyte co-cultures and there
      was a significant correlation between IGF-1 concentration and cardiomyocyte
      survival. We showed the activation of the IGF-1 receptor and its downstream
      molecular targets in cardiomyocytes co-cultured with c-kitpos GATA-4 high cCSCs
      but not in cardiomyocytes that were cultured alone, co-cultured with fibroblasts
      or c-kitpos GATA-4 low cCSCs. Addition of a blocking antibody specific to the IGF
      1 receptor inhibited the survival of cardiomyocytes and prevented the activation
      of its signalling in cardiomyocytes in the c-kitpos GATA-4 high
      cCSC/cardiomyocyte co-culture system. IGF-1 supplementation or IGF-1 high
      conditioned medium taken from the co-culture of c-kitpos GATA-4 high cCSCs plus
      cardiomyocytes did extend the survival and contractility of cardiomyocytes
      cultured alone and cardiomyocytes co-cultured with c-kitpos GATA-4 low cCSCs.
      CONCLUSION/SIGNIFICANCE: c-kitpos GATA-4 high cCSCs exert a paracrine survival
      effect on cardiomyocytes through induction of the IGF-1R and signalling pathway.

PMID- 21179205
TI  - Thermodynamics of competitive molecular channel transport: application to
      artificial nuclear pores.
AB  - In an analytical model channel transport is analyzed as a function of key
      parameters, determining efficiency and selectivity of particle transport in a
      competitive molecular environment. These key parameters are the concentration of
      particles, solvent-channel exchange dynamics, as well as particle-in-channel- and
      interparticle interaction. These parameters are explicitly related to
      translocation dynamics and channel occupation probability. Slowing down the
      exchange dynamics at the channel ends, or elevating the particle concentration
      reduces the in-channel binding strength necessary to maintain maximum transport.
      Optimized in-channel interaction may even shift from binding to repulsion. A
      simple equation gives the interrelation of access dynamics and concentration at
      this transition point. The model is readily transferred to competitive transport
      of different species, each of them having their individual in-channel affinity.
      Combinations of channel affinities are determined which differentially favor
      selectivity of certain species on the cost of others. Selectivity for a species
      increases if its in-channel binding enhances the species' translocation
      probability when compared to that of the other species. Selectivity increases
      particularly for a wide binding site, long channels, and fast access dynamics.
      Recent experiments on competitive transport of in-channel binding and inert
      molecules through artificial nuclear pores serve as a paradigm for our model. It
      explains qualitatively and quantitatively how binding molecules are favored for
      transport at the cost of the transport of inert molecules.

PMID- 21179206
TI  - Induction of heme oxygenase-1 can halt and even reverse renal tubule-interstitial
      fibrosis.
AB  - BACKGROUND: The tubule-interstitial fibrosis is the hallmark of progressive renal
      disease and is strongly associated with inflammation of this compartment. Heme
      oxygenase-1 (HO-1) is a cytoprotective molecule that has been shown to be
      beneficial in various models of renal injury. However, the role of HO-1 in
      reversing an established renal scar has not yet been addressed. AIM: We explored
      the ability of HO-1 to halt and reverse the establishment of fibrosis in an
      experimental model of chronic renal disease. METHODS: Sprague-Dawley male rats
      were subjected to unilateral ureteral obstruction (UUO) and divided into two
      groups: non-treated and Hemin-treated. To study the prevention of fibrosis,
      animals were pre-treated with Hemin at days -2 and -1 prior to UUO. To
      investigate whether HO-1 could reverse established fibrosis, Hemin therapy was
      given at days 6 and 7 post-surgery. After 7 and/or 14 days, animals were
      sacrificed and blood, urine and kidney tissue samples were collected for
      analyses. Renal function was determined by assessing the serum creatinine, inulin
      clearance, proteinuria/creatininuria ratio and extent of albuminuria. Arterial
      blood pressure was measured and fibrosis was quantified by Picrosirius staining.
      Gene and protein expression of pro-inflammatory and pro-fibrotic molecules, as
      well as HO-1 were performed. RESULTS: Pre-treatment with Hemin upregulated HO-1
      expression and significantly reduced proteinuria, albuminuria, inflammation and
      pro-fibrotic protein and gene expressions in animals subjected to UUO.
      Interestingly, the delayed treatment with Hemin was also able to reduce renal
      dysfunction and to decrease the expression of pro-inflammatory molecules, all in
      association with significantly reduced levels of fibrosis-related molecules and
      collagen deposition. Finally, TGF-beta protein production was significantly lower
      in Hemin-treated animals. CONCLUSION: Treatment with Hemin was able both to
      prevent the progression of fibrosis and to reverse an established renal scar.
      Modulation of inflammation appears to be the major mechanism behind HO-1
      cytoprotection.

PMID- 21179207
TI  - FYVE-dependent endosomal targeting of an arrestin-related protein in amoeba.
AB  - BACKGROUND: Visual and beta-arrestins are scaffolding proteins involved in the
      regulation of receptor-dependent intracellular signaling and their trafficking.
      The arrestin superfamilly includes several arrestin domain-containing proteins
      and the structurally related protein Vps26. In Dictyostelium discoideum, the
      arrestin-domain containing proteins form a family of six members, namely AdcA to 
      F. In contrast to canonical arrestins, Dictyostelium Adc proteins show a more
      complex architecture, as they possess, in addition to the arrestin core, other
      domains, such as C2, FYVE, LIM, MIT and SAM, which potentially mediate selective
      interactions with either lipids or proteins. METHODOLOGY AND PRINCIPAL FINDINGS:
      A detailed analysis of AdcA has been performed. AdcA extends on both sides of the
      arrestin core, in particular by a FYVE domain which mediates selective
      interactions with PI(3)P, as disclosed by intrinsic fluorescence measurements and
      lipid overlay assays. Localization studies showed an enrichment of tagged- and
      endogenous AdcA on the rim of early macropinosomes and phagosomes. This vesicular
      distribution relies on a functional FYVE domain. Our data also show that the
      arrestin core binds the ADP-ribosylation factor ArfA, the unique amoebal Arf
      member, in its GDP-bound conformation. SIGNIFICANCE: This work describes one of
      the 6 arrestin domain-containing proteins of Dictyostelium, a novel and atypical
      member of the arrestin clan. It provides the basis for a better understanding of
      arrestin-related protein involvement in trafficking processes and for further
      studies on the expanding roles of arrestins in eukaryotes.

PMID- 21179208
TI  - The spinal cord expression of neuronal and inducible nitric oxide synthases and
      their contribution in the maintenance of neuropathic pain in mice.
AB  - BACKGROUND: Nitric oxide generated by neuronal (NOS1), inducible (NOS2) or
      endothelial (NOS3) nitric oxide synthases contributes to pain processing, but the
      exact role of NOS1 and NOS2 in the maintenance of chronic peripheral neuropathic
      pain as well as the possible compensatory changes in their expression in the
      spinal cord of wild type (WT) and NOS knockout (KO) mice at 21 days after total
      sciatic nerve ligation remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: The
      mechanical and thermal allodynia as well as thermal hyperalgesia induced by
      sciatic nerve injury was evaluated in WT, NOS1-KO and NOS2-KO mice from 1 to 21
      days after surgery. The mRNA and protein levels of NOS1, NOS2 and NOS3 in the
      spinal cord of WT and KO mice, at 21 days after surgery, were also assessed.
      Sciatic nerve injury led to a neuropathic syndrome in WT mice, in contrast to the
      abolished mechanical allodynia and thermal hyperalgesia as well as the decreased
      or suppressed thermal allodynia observed in NOS1-KO and NOS2-KO animals,
      respectively. Sciatic nerve injury also increases the spinal cord expression of
      NOS1 and NOS2 isoforms, but not of NOS3, in WT and NOS1-KO mice respectively.
      Moreover, the presence of NOS2 is required to increase the spinal cord expression
      of NOS1 whereas an increased NOS1 expression might avoid the up-regulation of
      NOS2 in the spinal cord of nerve injured WT mice. CONCLUSIONS/SIGNIFICANCE: These
      data suggest that the increased spinal cord expression of NOS1, regulated by
      NOS2, might be responsible for the maintenance of chronic peripheral neuropathic
      pain in mice and propose these enzymes as interesting therapeutic targets for
      their treatment.

PMID- 21179209
TI  - Co-conserved features associated with cis regulation of ErbB tyrosine kinases.
AB  - BACKGROUND: The epidermal growth factor receptor kinases, or ErbB kinases, belong
      to a large sub-group of receptor tyrosine kinases (RTKs), which share a conserved
      catalytic core. The catalytic core of ErbB kinases have functionally diverged
      from other RTKs in that they are activated by a unique allosteric mechanism that
      involves specific interactions between the kinase core and the flanking
      Juxtamembrane (JM) and COOH-terminal tail (C-terminal tail). Although extensive
      studies on ErbB and related tyrosine kinases have provided important insights
      into the structural basis for ErbB kinase functional divergence, the sequence
      features that contribute to the unique regulation of ErbB kinases have not been
      systematically explored. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we use a
      Bayesian approach to identify the selective sequence constraints that most
      distinguish ErbB kinases from other receptor tyrosine kinases. We find that
      strong ErbB kinase-specific constraints are imposed on residues that tether the
      JM and C-terminal tail to key functional regions of the kinase core. A conserved
      RIxKExE motif in the JM-kinase linker region and a glutamine in the inter-lobe
      linker are identified as two of the most distinguishing features of the ErbB
      family. While the RIxKExE motif tethers the C-terminal tail to the N-lobe of the
      kinase domain, the glutamine tethers the C-terminal tail to hinge regions
      critical for inter-lobe movement. Comparison of the active and inactive crystal
      structures of ErbB kinases indicates that the identified residues are
      conformationally malleable and can potentially contribute to the cis regulation
      of the kinase core by the JM and C-terminal tail. ErbB3, and EGFR orthologs in
      sponges and parasitic worms, diverge from some of the canonical ErbB features,
      providing insights into sub-family and lineage-specific functional
      specialization. CONCLUSION/SIGNIFICANCE: Our analysis pinpoints key residues for
      mutational analysis, and provides new clues to cancer mutations that alter the
      canonical modes of ErbB kinase regulation.

PMID- 21179210
TI  - No detectable fertility benefit from a single additional mating in wild stalk
      eyed flies.
AB  - BACKGROUND: Multiple mating by female insects is widespread, and the
      explanation(s) for repeated mating by females has been the subject of much
      discussion. Females may profit from mating multiply through direct material
      benefits that increase their own reproductive output, or indirect genetic
      benefits that increase offspring fitness. One particular direct benefit that has
      attracted significant attention is that of fertility assurance, as females often
      need to mate multiply to achieve high fertility. This hypothesis has never been
      tested in a wild insect population. METHODOLOGY/PRINCIPAL FINDINGS: Female
      Malaysian stalk-eyed flies (Teleopsis dalmanni) mate repeatedly during their
      lifetime, and have been shown to be sperm limited under both laboratory and field
      conditions. Here we ask whether receiving an additional mating alleviates sperm
      limitation in wild females. In our experiment one group of females received a
      single additional mating, while a control group received an interrupted, and
      therefore unsuccessful, mating. Females that received an additional mating did
      not lay more fertilised eggs in total, nor did they lay proportionately more
      fertilised eggs. Female fertility declined significantly through time,
      demonstrating that females were sperm limited. However, receipt of an additional
      mating did not significantly alter the rate of this decline.
      CONCLUSIONS/SIGNIFICANCE: Our data suggest that the fertility consequences of a
      single additional mating were small. We discuss this effect (or lack thereof),
      and suggest that it is likely to be attributed to small ejaculate size, a high
      proportion of failed copulations, and the presence of X-linked meiotic drive in
      this species.

PMID- 21179211
TI  - Cytokine profiles in asthma families depend on age and phenotype.
AB  - BACKGROUND: Circulating cytokine patterns may be relevant for the diagnosis of
      asthma, for the discrimination of certain phenotypes, and prognostic factors for
      exacerbation of disease. METHODOLOGY/PRINCIPAL FINDINGS: In this study we
      investigated serum samples from 944 individuals of 218 asthma-affected families
      by a multiplex, microsphere based system detecting at high sensitivity eleven
      asthma associated mediators: eotaxin (CCL11), granulocyte macrophage stimulating
      factor (GM-CSF), interferon gamma (IFNgamma), interleukin-4 (IL-4), IL-5, IL-8,
      IL-10, IL-12 (p40), IL-13, IL-17 and tumor necrosis factor alpha (TNFalpha).
      Single cytokine levels were largely similar between asthmatic and healthy
      individuals when analysing asthma as single disease entity. Regulatory
      differences between parental and pediatric asthma were reflected by six of the
      eleven mediators analyzed (eotaxin, IL-4, IL-5, IL-10, IL-12, TNFalpha). IL-12
      (p40) and IL-5 were the best predictor for extrinsic asthma in children with an
      increased odds ratio of 2.85 and 1.96 per log pg/ml increase (IL-12 (p40): 1.2
      6.8, p=0.019, and IL-5: 1.2-2.5, p=0.025). Frequent asthma attacks in children
      are associated with elevated IL-5 serum levels (p=0.013). Cytokine patterns seem
      to be individually balanced in both, healthy and diseased adults and children,
      with various cytokines correlating among each other (IL-17 and IFNgamma
      (rs=0.67), IL-4 and IL-5 (rs=0.55), IFNgamma and GM-CSF (rs=0.54)).
      CONCLUSION/SIGNIFICANCE: Our data support mainly an age- but also an asthma
      phenotype-dependent systemic immune regulation.

PMID- 21179212
TI  - Fiber type conversion by PGC-1alpha activates lysosomal and autophagosomal
      biogenesis in both unaffected and Pompe skeletal muscle.
AB  - PGC-1alpha is a transcriptional co-activator that plays a central role in the
      regulation of energy metabolism. Our interest in this protein was driven by its
      ability to promote muscle remodeling. Conversion from fast glycolytic to slow
      oxidative fibers seemed a promising therapeutic approach in Pompe disease, a
      severe myopathy caused by deficiency of the lysosomal enzyme acid alpha
      glucosidase (GAA) which is responsible for the degradation of glycogen. The
      recently approved enzyme replacement therapy (ERT) has only a partial effect in
      skeletal muscle. In our Pompe mouse model (KO), the poor muscle response is seen
      in fast but not in slow muscle and is associated with massive accumulation of
      autophagic debris and ineffective autophagy. In an attempt to turn the therapy
      resistant fibers into fibers amenable to therapy, we made transgenic KO mice
      expressing PGC-1alpha in muscle (tgKO). The successful switch from fast to slow
      fibers prevented the formation of autophagic buildup in the converted fibers, but
      PGC-1alpha failed to improve the clearance of glycogen by ERT. This outcome is
      likely explained by an unexpected dramatic increase in muscle glycogen load to
      levels much closer to those observed in patients, in particular infants, with the
      disease. We have also found a remarkable rise in the number of lysosomes and
      autophagosomes in the tgKO compared to the KO. These data point to the role of
      PGC-1alpha in muscle glucose metabolism and its possible role as a master
      regulator for organelle biogenesis - not only for mitochondria but also for
      lysosomes and autophagosomes. These findings may have implications for therapy of
      lysosomal diseases and other disorders with altered autophagy.

PMID- 21179213
TI  - Receptor-mediated enhancement of beta adrenergic drug activity by ascorbate in
      vitro and in vivo.
AB  - RATIONALE: Previous in vitro research demonstrated that ascorbate enhances
      potency and duration of activity of agonists binding to alpha 1 adrenergic and
      histamine receptors. OBJECTIVES: Extending this work to beta 2 adrenergic systems
      in vitro and in vivo. METHODS: Ultraviolet spectroscopy was used to study
      ascorbate binding to adrenergic receptor preparations and peptides. Force
      transduction studies on acetylcholine-contracted trachealis preparations from
      pigs and guinea pigs measured the effect of ascorbate on relaxation due to
      submaximal doses of beta adrenergic agonists. The effect of inhaled albuterol
      with and without ascorbate was tested on horses with heaves and sheep with
      carbachol-induced bronchoconstriction. MEASUREMENTS: Binding constants for
      ascorbate binding to beta adrenergic receptor were derived from concentration
      dependent spectral shifts. Dose- dependence curves were obtained for the
      relaxation of pre-contracted trachealis preparations due to beta agonists in the
      presence and absence of varied ascorbate. Tachyphylaxis and fade were also
      measured. Dose response curves were determined for the effect of albuterol plus
      and-minus ascorbate on airway resistance in horses and sheep. MAIN RESULTS:
      Ascorbate binds to the beta 2 adrenergic receptor at physiological
      concentrations. The receptor recycles dehydroascorbate. Physiological and supra
      physiological concentrations of ascorbate enhance submaximal epinephrine and
      isoproterenol relaxation of trachealis, producing a 3-10-fold increase in
      sensitivity, preventing tachyphylaxis, and reversing fade. In vivo, ascorbate
      improves albuterol's effect on heaves and produces a 10-fold enhancement of
      albuterol activity in "asthmatic" sheep. CONCLUSIONS: Ascorbate enhances beta
      adrenergic activity via a novel receptor-mediated mechanism; increases potency
      and duration of beta adrenergic agonists effective in asthma and COPD; prevents
      tachyphylaxis; and reverses fade. These novel effects are probably caused by a
      novel mechanism involving phosphorylation of aminergic receptors and have
      clinical and drug-development applications.

PMID- 21179214
TI  - VKORC1 pharmacogenetics and pharmacoproteomics in patients on warfarin
      anticoagulant therapy: transthyretin precursor as a potential biomarker.
AB  - BACKGROUND: Recognizing specific protein changes in response to drug
      administration in humans has the potential for the development of personalized
      medicine. Such changes can be identified by pharmacoproteomics approach based on
      proteomic technologies. It can also be helpful in matching a particular target
      based therapy to a particular marker in a subgroup of patients, in addition to
      the profile of genetic polymorphism. Warfarin is a commonly prescribed oral
      anticoagulant in patients with prosthetic valve disease, venous thromboembolism
      and stroke. METHODS AND FINDING: We used a combined pharmacogenetics and iTRAQ
      coupled LC-MS/MS pharmacoproteomics approach to analyze plasma protein profiles
      of 53 patients, and identified significantly upregulated level of transthyretin
      precursor in patients receiving low dose of warfarin but not in those on high
      dose of warfarin. In addition, real-time RT-PCR, western blotting, human IL-6
      ELISA assay were done for the results validation. CONCLUSION: This combined
      pharmacogenomics and pharmacoproteomics approach may be applied for other target
      based therapies, in matching a particular marker in a subgroup of patients, in
      addition to the profile of genetic polymorphism.

PMID- 21179215
TI  - The effects of nutrient enrichment and herbivore abundance on the ability of turf
      algae to overgrow coral in the Caribbean.
AB  - Turf algae are multispecies communities of small marine macrophytes that are
      becoming a dominant component of coral reef communities around the world. To
      assess the impact of turf algae on corals, we investigated the effects of
      increased nutrients (eutrophication) on the interaction between the Caribbean
      coral Montastraea annularis and turf algae at their growth boundary. We also
      assessed whether herbivores are capable of reducing the abundance of turf algae
      at coral-algae boundaries. We found that turf algae cause visible (overgrowth)
      and invisible negative effects (reduced fitness) on neighbouring corals. Corals
      can overgrow neighbouring turf algae very slowly (at a rate of 0.12 mm 3 wk(-1))
      at ambient nutrient concentrations, but turf algae overgrew corals (at a rate of
      0.34 mm 3 wk(-1)) when nutrients were experimentally increased. Exclusion of
      herbivores had no measurable effect on the rate turf algae overgrew corals. We
      also used PAM fluorometry (a common approach for measuring of a colony's
      "fitness") to detect the effects of turf algae on the photophysiology of
      neighboring corals. Turf algae always reduced the effective photochemical
      efficiency of neighbouring corals, regardless of nutrient and/or herbivore
      conditions. The findings that herbivores are not capable of controlling the
      abundance of turf algae and that nutrient enrichment gives turf algae an overall
      competitive advantage over corals together have serious implications for the
      health of Caribbean coral reef systems. At ambient nutrient levels, traditional
      conservation measures aimed at reversing coral-to-algae phase shifts by reducing
      algal abundance (i.e., increasing herbivore populations by establishing Marine
      Protected Areas or tightening fishing regulations) will not necessarily reduce
      the negative impact of turf algae on local coral communities. Because turf algae
      have become the most abundant benthic group on Curacao (and likely elsewhere in
      the Caribbean), new conservation strategies are required to mitigate their
      negative impact on coral communities.

PMID- 21179217
TI  - Case of primary diffuse large B-cell lymphoma of lacrimal sac in a Japanese
      patient.
AB  - The purpose of this study was to determine the characteristics of primary diffuse
      large B-cell lymphoma (DLBCL) of the lacrimal sac. A 77-year-old man had epiphora
      of the right eye for three years. After visiting five clinics and hospitals, he
      was referred to our hospital, and the preoperative magnetic resonance imaging
      findings suggested a lacrimal sac mass. Dacryocysteography showed an obstruction
      of the right nasolacrimal duct, so we performed dacryocystectomy. After a
      histopathologic examination of the specimen, the patient was diagnosed with a
      DLBCL. Positron emission tomography scanning excluded metastases, and the final
      diagnosis was made of a primary DLBCL of the right lacrimal sac. He underwent
      radiotherapy with 30.6 Gray in total to the right lacrimal sac. After
      radiotherapy, no recurrence has been observed anywhere in his body for one year.
      Although a malignant lymphoma of the lacrimal sac is rare, clinicians should
      consider a primary malignant lymphoma in the differential diagnosis in patients
      with chronic dacryocystitis.

PMID- 21179216
TI  - Chromatin remodeling pathways in smooth muscle cell differentiation, and evidence
      for an integral role for p300.
AB  - BACKGROUND: Phenotypic alteration of vascular smooth muscle cells (SMC) in
      response to injury or inflammation is an essential component of vascular disease.
      Evidence suggests that this process is dependent on epigenetic regulatory
      processes. P300, a histone acetyltransferase (HAT), activates crucial muscle
      specific promoters in terminal (non-SMC) myocyte differentiation, and may be
      essential to SMC modulation as well. RESULTS: We performed a subanalysis
      examining transcriptional time-course microarray data obtained using the A404
      model of SMC differentiation. Numerous chromatin remodeling genes (up to 62% of
      such genes on our array platform) showed significant regulation during
      differentiation. Members of several chromatin-remodeling families demonstrated
      involvement, including factors instrumental in histone modification, chromatin
      assembly-disassembly and DNA silencing, suggesting complex, multi-level systemic
      epigenetic regulation. Further, trichostatin A, a histone deacetylase inhibitor,
      accelerated expression of SMC differentiation markers in this model. Ontology
      analysis indicated a high degree of p300 involvement in SMC differentiation, with
      60.7% of the known p300 interactome showing significant expression changes.
      Knockdown of p300 expression accelerated SMC differentiation in A404 cells and
      human SMCs, while inhibition of p300 HAT activity blunted SMC differentiation.
      The results suggest a central but complex role for p300 in SMC phenotypic
      modulation. CONCLUSIONS: Our results support the hypothesis that chromatin
      remodeling is important for SMC phenotypic switching, and detail wide-ranging
      involvement of several epigenetic modification families. Additionally, the
      transcriptional coactivator p300 may be partially degraded during SMC
      differentiation, leaving an activated subpopulation with increased HAT activity
      and SMC differentiation-gene specificity.

PMID- 21179218
TI  - Efficacy, safety, and tolerability of travoprost 0.004% BAK-free versus prior
      treatment with latanoprost 0.005% in Japanese patients.
AB  - OBJECTIVE: To examine the efficacy, safety, and tolerability of travoprost 0.004%
      benzalkonium chloride (BAK)-free compared with previous use of latanoprost 0.005%
      in Japanese patients living in the US who had primary open-angle glaucoma or
      ocular hypertension. METHODS: This was an open-label, multicenter, bilateral,
      intraindividual, and active-controlled study in which 20 Japanese American
      patients with primary open-angle glaucoma or ocular hypertension who had been on
      latanoprost 0.005% monotherapy were changed to monotherapy with travoprost 0.004%
      BAK-free daily for 12 weeks. Patients were administered the same series of tests
      to evaluate the efficacy, safety, and tolerability of latanoprost at the baseline
      visit and of travoprost BAK-free at the week 12 visit. RESULTS: No significant
      difference in mean intraocular pressure (IOP) was observed between latanoprost
      monotherapy at baseline and travoprost BAK-free monotherapy after 12 weeks (P =
      0.76), nor were significant differences noted in mean ocular hyperemia, visual
      acuity, corneal fluorescein staining, or overall scores from the Ocular Surface
      Disease Index. Patients had a significantly shorter mean tear breakup time while
      on latanoprost compared with travoprost BAK-free (P = 0.0094). Significantly more
      patients preferred travoprost BAK-free monotherapy over latanoprost monotherapy
      (14 versus 6; P = 0.011). CONCLUSION: The results of this study suggest that
      Japanese American patients transitioned from latanoprost 0.005% monotherapy to
      travoprost 0.004% BAK-free can expect similar IOP control and some improvement in
      anterior segment signs. This transition study showed a strong patient preference
      for travoprost BAK-free over latanoprost, at a ratio of more than 2:1.

PMID- 21179219
TI  - International vision requirements for driver licensing and disability pensions:
      using a milestone approach in characterization of progressive eye disease.
AB  - OBJECTIVE: Low vision that causes forfeiture of driver's licenses and collection
      of disability pension benefits can lead to negative psychosocial and economic
      consequences. The purpose of this study was to review the requirements for
      holding a driver's license and rules for obtaining a disability pension due to
      low vision. Results highlight the possibility of using a milestone approach to
      describe progressive eye disease. METHODS: Government and research reports,
      websites, and journal articles were evaluated to review rules and requirements in
      Germany, Spain, Italy, France, the UK, and the US. RESULTS: Visual acuity limits
      are present in all driver's license regulations. In most countries, the visual
      acuity limit is 0.5. Visual field limits are included in some driver's license
      regulations. In Europe, binocular visual field requirements typically follow the
      European Union standard of >=120 degrees . In the US, the visual field
      requirements are typically between 110 degrees  and 140 degrees . Some countries
      distinguish between being partially sighted and blind in the definition of legal
      blindness, and in others there is only one limit. CONCLUSIONS: Loss of driving
      privileges could be used as a milestone to monitor progressive eye disease.
      Forfeiture could be standardized as a best-corrected visual acuity of <0.5 or
      visual field of <120 degrees , which is consistent in most countries. However,
      requirements to receive disability pensions were too variable to standardize as
      milestones in progressive eye disease. Implementation of the World Health
      Organization criteria for low vision and blindness would help to establish better
      comparability between countries.

PMID- 21179220
TI  - Central corneal thickness in black Cameroonian ocular hypertensive and
      glaucomatous subjects.
AB  - PURPOSE: To evaluate central corneal thickness (CCT) in a black Cameroonian
      population of ocular hypertensive and glaucomatous subjects. MATERIAL AND
      METHODS: This was a prospective study undertaken with an ultrasonic pachymeter
      from January 2009 to December 2009 in an eye clinic (INNEL Medical center) in
      Yaounde, Cameroon. RESULTS: One hundred subjects (200 eyes) were enrolled in the
      study. Sixty subjects were glaucomatous (primary open angle glaucoma, POAG
      group), and 40 ocular hypertensive (OHT group). The mean age of the sample was
      52.60 +/- 12.23 years. For the whole sample, CCT was 534.71 +/- 37.95 MUm in the
      right eye and 533.61 +/- 37.67 MUm in the left eye, with no statistically
      significant difference between the 2 eyes (P = 0.446). CCT in the POAG group was
      526.30 +/- 37.34 MUm in the right eye and 524.90 +/- 35.92 MUm in the left eye.
      CCT in the OHT group was 547.32 +/- 35.71 MUm in the right eye and 546.67 +/-
      36.85 MUm in the left eye. There was a statistically significant difference
      between CCT of the 2 groups (right eye: P = 0.013; left eye: P = 0.007).
      CONCLUSION: Mean CCT of ocular hypertensive subjects was thicker than CCT of
      glaucomatous ones in our Cameroonian sample. However, in both ocular hypertensive
      or glaucomatous patients, CCT of black Cameroonians is thinner than that reported
      in other studies in Caucasian populations.

PMID- 21179221
TI  - Central serous papillopathy by optic nerve head drusen.
AB  - We report a 38-year-old man with a complaint of blurred vision in his right eye
      for the previous 5 days. He had bilateral optic disc drusen. Fluorescein
      angiography revealed multiple hyperfluorescent foci within temporal optic discs
      and temporal inferior arcade in late phase. Optical coherence tomography showed
      bilateral peripapillary serous detachment as well as right macular detachment.
      This is the first reported case of a concurrent peripapillary and macular
      detachment in a patient with central serous papillopathy by optic disc drusen.
      Central serous papillopathy is an atypical form of central serous
      chorioretinopathy that should be considered as a potential cause of acute loss of
      vision in patients with optic nerve head drusen.

PMID- 21179222
TI  - Doppler ultrasound and giant cell arteritis.
AB  - OBJECTIVE: To evaluate the utility of ultrasound in aiding the diagnosis of giant
      cell arteritis (GCA), in monitoring the response to corticotherapy, and in
      detecting early relapses. METHODS: A pilot study, prospective, included 10
      patients with suspected GCA. All patients underwent ultrasound examination of
      both temporal arteries before temporal artery biopsy (TAB), 3 weeks after
      starting treatment, and 3 months after diagnosis. For this study, the
      histological findings alone were used to define if patients were suffering from
      GCA. The findings on ultrasound were compared with the results of biopsy. The
      best place to perform TAB was observed by ultrasound. RESULTS: All patients with
      positive biopsy were detected with ultrasound. No false positives were observed
      on ultrasound. The results presented give a sensibility, specificity, and
      positive predictive value of 100% for the use of ultrasound in the diagnosis of
      GCA. Two relapses were detected early by ultrasound during the follow-up.
      CONCLUSIONS: This pilot study suggests that eco-doppler may be a useful tool in
      diagnosis and clinic follow-up in patients with suspected GCA.

PMID- 21179223
TI  - Association between assisted reproductive technology and advanced retinopathy of
      prematurity.
AB  - PURPOSE: To investigate the associations between assisted reproductive technology
      (ART) and severe retinopathy of prematurity (ROP) requiring treatment. METHODS:
      Retrospective analyses of inborn preterm infants screened for severe ROP at the
      Weill Cornell Medical Center Neonatal Intensive Care Unit at the New York
      Presbyterian Hospital by single factor logistic regression and multifactor
      models. RESULTS: Of 399 ethnically diverse infants, 253 were conceived naturally
      and 146 by ART. Eight (3.16%) patients conceived naturally, and 11 (7.53%) with
      ART required laser treatment. In multifactor analyses, significant risks for
      severe ROP requiring treatment included both gestational age (odds ratio [OR]
      0.34; 95% confidence interval [CI] 0.23-0.52; P < 0.001) and ART ([OR] 4.70;
      [CI], 1.52-4.57; P = 0.007). CONCLUSIONS: ART is associated with severe ROP
      requiring treatment in this cohort. This is the first report that demonstrates a
      statistically significant association between ART and severe ROP requiring
      treatment in infants in the US.

PMID- 21179224
TI  - Intraocular pressure changes following the use of silicone oil or Densiron 68 as
      endotamponade in pars plana vitrectomy.
AB  - OBJECTIVE: To compare the effects of standard silicone oil 5700 (SSO) and heavy
      silicone oil (HSO) such as Densiron((r)) 68 on intraocular pressure (IOP).
      MATERIALS AND METHODS: Retrospective case series including 180 eyes (105 treated
      with SSO and 75 with HSO). IOP was measured before surgery, 1 day after, and then
      at 1-, 3-, 6-, and 12-month follow-ups. RESULTS: In the SSO group, a significant
      increase in IOP occurred in 14% of the eyes (15/105) at 1 day postoperatively,
      and persisted in 11.4% (12/105) at 1-month follow-up. In the HSO group, a
      persistent elevated IOP was recorded in 20% of the eyes (15/75) at 1 day
      postoperatively, and in 16% (12/75) at 1-month follow-up. At 12-month follow-up,
      mean IOP was 16.7 +/- 8.7 mmHg and 19.7 +/- 3.8 mmHg, respectively, in the SSO
      and HSO groups. The difference between the 2 groups was always not significant.
      CONCLUSION: Overall, the use of Densiron 68 was not associated with higher IOP
      values as compared with SSO.

PMID- 21179225
TI  - Japanese case of follicular lymphoma of ocular adnexa diagnosed by
      clinicopathologic, immunohistochemical, and molecular genetic techniques.
AB  - BACKGROUND: Follicular lymphomas of the ocular adnexa are very rare in Japan,
      with only two reported cases. CASE: A 44-year-old woman visited our clinic for
      treatment of ocular adnexal tumors in both eyes. FINDINGS: Histologic examination
      showed that the neoplastic lesions consisted of atypical lymphoid cells, and the
      tentative diagnosis was malignant lymphoma. Immunophenotypic analyses by flow
      cytometry and immunohistochemistry showed that the atypical lymphoid cells
      expressed CD45, bcl-2, CD10, CD19, CD20, IgM, and kappa light chains. The cells
      were negative for CD5 and other T, natural killer, or myelomonocyte antigens.
      Southern blot hybridization demonstrated gene rearrangement bands in the
      immunoglobulin JH region. Fluorescence in situ hybridization studies showed a
      translocation at t(14,18)(q32,q21). Systemic evaluations detected enlargements of
      both the inguinal lymph nodes and parabronchial lymph nodes. CONCLUSION: Our
      results show that flow cytometry, molecular genetic analyses, and chromosomal
      examination can be useful in differentiating follicular lymphoma from marginal
      zone B cell lymphoma of mucosa-associated lymphoid tissue and reactive lymphoid
      hyperplasia.

PMID- 21179226
TI  - Ocular pharmacokinetics of 0.45% ketorolac tromethamine.
AB  - PURPOSE: A new carboxymethylcellulose (CMC)-containing ophthalmic formulation of
      0.45% ketorolac, pH 6.8 (Acuvail((r))) was recently developed for treatment of
      inflammation and pain after cataract surgery. This study compared
      pharmacokinetics of the new formulation with that of a prior formulation, 0.4%
      ketorolac, pH 7.4 (Acular LS((r))). METHODS: Ketorolac formulations were
      administered bilaterally (35 MUL) to female New Zealand White rabbits. Samples
      from aqueous humor and iris-ciliary body were collected at multiple time points,
      and ketorolac was quantified using liquid chromatography-tandem mass
      spectrometry. RESULTS: In aqueous humor, the peak concentration (C(max)) and area
      under the concentration-time curve (AUC(0-tau)) of ketorolac were, respectively,
      389 ng/mL and 939 ng.h/mL following administration of the CMC-containing 0.45%
      ketorolac, pH 6.8, and 211 ng/mL and 465 ng.hr/mL following administration of the
      0.4% ketorolac, pH 7.4. In iris-ciliary body, C(max) and AUC(0-tau) of ketorolac
      were, respectively 450 ng/g and 2040 ng.h/g after administration of the CMC
      containing 0.45% ketorolac, pH 6.8, and 216 ng/g and 699 ng.h/g after
      administration of the 0.4% ketorolac, pH 7.4. PK simulations predicted an AUC(0
      tau) of 2910 ng.h/g for twice daily, CMC-containing 0.45% ketorolac, pH 6.8,
      compared to 725 ng.h/g for 4 times daily, 0.4% ketorolac, pH 7.4. CONCLUSIONS:
      The CMC-containing formulation of 0.45% ketorolac, pH 6.8, increased ketorolac
      bioavailability by 2-fold in aqueous humor and by 3-fold in iris-ciliary body in
      comparison to the 0.4% ketorolac, pH 7.4, allowing a reduced dosing schedule from
      4 times daily to twice daily.

PMID- 21179227
TI  - Preparation and characterization of microporous poly(D,L-lactic acid) film for
      tissue engineering scaffold.
AB  - We prepared a series of microporous films based on poly(d,l-lactic acid) (PLA)
      via phase separation. According to scanning electron microscopy (SEM), a 3
      dimensional foamy structure with multimicrometer scale pores on the air surface
      of film could be observed. As the morphology of PLA film could not be stabilized
      using solvent-nonsolvent phase separation, we investigated the effect of
      temperature, air movement, and concentration on the properties of microporous PLA
      films. The results show that when the temperature was 25 degrees C in a vacuum,
      it was easy to prepare PLA film with micropores, and it was stable. As the
      relationship between the morphology and formation factors was clear and the
      morphology of the PLA film was controllable, we studied the PLA film's potential
      use for cell culture. SEM results showed that NIH3T3 cell could be adhered on the
      surface of film well after incubation for 2 days. Meanwhile, in vitro culture
      experiments revealed the great biocompatibility of the scaffold for adsorption
      and proliferation of fibroblasts.

PMID- 21179228
TI  - Evaluation of the Learning Environment for Diploma in Family Medicine with the
      Dundee Ready Education Environment (DREEM) Inventory.
AB  - The primary healthcare system is at a turning point in Saudi Arabia. However, the
      sustainability of family medicine as the core element of that system is
      increasingly being called into question because of lack of family physicians. In
      keeping view this problem; a postgraduate diploma program in family medicine has
      started in 2008. A validated measure of educational environment i.e., Dundee
      Ready Education Environment (DREEM) questionnaire consisting of 50 questions
      having five domains of perception was administered to all 13 trainees of the
      diploma course at the completion of the program to check their perception about
      learning evironment. The trainees comprised of 4 males (40%) and 6 females (60%).
      The overall score showed more positive than negative side (147/200). There is no
      significant difference (P > 0.05) in the mean scores of five different domains of
      perception. The subclasses of five domains showed that teaching perceived as
      positive by 50%, moving towards right direction by 80%, feeling more positive by
      50%, positive attitude by 80% and the 70% scored the course as not too bad. The
      overall high score and positive attitude towards the course assures the better
      teaching environment. However, there are areas to improve and it requires
      continuous evaluation.

PMID- 21179229
TI  - Senior Resident Training on Educational Principles (STEP): A Proposed Innovative
      Step from a Developing Nation.
AB  - Resident-as-teacher courses are pretty common in Western medical schools however
      they are a rarity in Asian and developing countries. The current report is a
      scholarly analysis of a three day orientation program for senior residents in
      order to improve their functioning by providing new template either for
      supplementing basic workshops for faculty or to advocate a change in system. The
      experience gained by Medical Education Unit of University College of Medical
      Sciences can be used to conduct training breeding grounds at national or regional
      levels. Resident as teachers educational interventions need to be designed taking
      into account their impact on education system.

PMID- 21179230
TI  - Introduction and administration of the clinical skill test of the medical
      licensing examination, republic of Korea (2009).
AB  - The first trial of the clinical skill test as part of the Korean Medical
      Licensing Examination was done from September 23 to December 1, 2009, in the
      clinical skill test center located in the National Health Personnel Licensing
      Examination Board (NHPLEB) building, Seoul. Korea is the first country to
      introduce the clinical skill test as part of the medical licensing examination in
      Asia. It is a report on the introduction and administration of the test. The
      NHPLEB launched researches on the validity of introducing the clinical skill test
      and on the best implementation methods in 2000. Since 2006, lists of subjects of
      test items for the clinical skill test has been developed. The test consisted of
      two types of evaluation, i.e., a clinical performance examination (CPX) with a
      standardized patient (SP) and objective structured clinical examination (OSCE).
      The proctor (medical faculty member) and SP rate the examinees' proficiency for
      the OSCE and CPX respectively. Out of 3,456 applicants, 3,289 examinees (95.2%)
      passed the test. Out of 167 examinees who failed the clinical skill test, 142
      passed the written test. This means that the clinical skill test showed
      characteristics independent from the written test. This successful implementation
      of the clinical skill test is going to improve the medical graduates' performance
      of clinical skills.

PMID- 21179231
TI  - Failed Examinees' Legal Challenge over the Clinical Skill Test in the Korean
      Medical Licensing Examination.

PMID- 21179232
TI  - Stability of active zone components at the photoreceptor ribbon complex.
AB  - PURPOSE: Photoreceptor ribbon synapses translate light-dependent changes of
      membrane potential into graded transmitter release over several orders of
      magnitude in intensity. A specialized organelle at the active zone--the synaptic
      ribbon--is a key player in this process, and it is well known that the ribbon
      undergoes illumination and thus activity-dependent structural changes. However,
      the molecular basis for these changes is unknown. The aim of this study was to
      correlate the known ultrastructural ribbon changes to the distribution of
      proteins of the presynaptic ribbon complex. METHODS: In an in vitro assay, two
      distinct structural ribbon states--club-shaped and spherical-shaped--were
      enriched and the distribution of presynaptic proteins at the rod photoreceptor
      ribbon complex was analyzed with immunocytochemistry and light and electron
      microscopy. RESULTS: We show that structural changes of the ribbon correlate with
      the redistribution of selected presynaptic proteins. The disassembly of the
      ribbon complex seems to be a multistep process, which starts with the removal of
      spherical ribbon material while arciform density and active zone plasma membrane
      proteins remain largely unchanged at their synaptic location. Only later, in a
      second phase following the removal of ribbon material, the arciform density and
      plasma membrane proteins are redistributed from their synaptic localization and
      active zones disappear. CONCLUSIONS: The results of our study show that
      photoreceptor ribbon and arciform density/plasma membrane components might be
      influenced differentially by activity-driven processes, thus providing a
      molecular basis for further investigation of regulatory and adaptive processes in
      photoreceptor ribbon synaptic transmission.

PMID- 21179233
TI  - Clinical and genetic characterization of a Danish family with North Carolina
      macular dystrophy.
AB  - PURPOSE: To describe the phenotype of a family with an autosomal dominant macular
      dystrophy and identify the chromosomal location of the gene that causes this
      phenotype. METHODS: Twelve members of a three-generation family underwent routine
      clinical examination, including fundus photography. Four of the patients
      underwent extended examination with Goldmann perimetry, full-field
      electroretinogram, dark adaptation, and color vision testing, and two patients
      underwent optical coherence tomography and fundus autofluorescence examination.
      DNA samples were obtained from 12 family members and 3 spouses and genotyped at
      the known North Carolina Macular Dystrophy (NCMD) locus on chromosome 6q (MCDR1:
      OMIM 136550) using short tandem repeat polymorphisms. DNA samples were
      subsequently examined with a genome-wide scan of single nucleotide polymorphisms
      and the genotypes that were produced were studied with linkage and haplotype
      analyses. RESULTS: The 10 affected family members had clinical findings of
      macular lesions that are typical for NCMD. The small drusen-like yellowish
      lesions of mild NCMD were hyperautofluorescent. Hyperpigmented foveal lesions
      were surrounded by a zone of confluent hyperautofluorescence. Linkage analysis of
      short tandem repeat polymorphism genetic markers excluded the NCMD locus on
      chromosome 6. However, analysis of single nucleotide polymorphism genotypes from
      a genome-wide scan showed that NCMD in our pedigree is linked to a region on
      chromosome 5p that overlaps the previously mapped macular dystrophy (MCDR3) locus
      with a maximum log of the odds (LOD) score of 2.69 at a recombination fraction of
      0.00 (markers D5S406, D5S1987, and D5S2505). DISCUSSION: We report the first
      pedigree with NCMD from Scandinavia, and the first confirmation that a gene for
      this condition is located on chromosome 5p13-p15. The bright elements or lesions
      typical of NCMD differed from drusen in that no sign of accumulation of material
      between the retinal pigment epithelium and Bruch's membrane was seen. While the
      present study has found indications that the elements are located in the
      outermost layers of the retina, their precise location remains to be identified
      directly.

PMID- 21179234
TI  - Adipose-derived stem cells differentiate to keratocytes in vitro.
AB  - PURPOSE: Adipose-derived stem cells (ADSC) are an abundant population of adult
      stem cells with the potential to differentiate into several specialized tissue
      types, including neural and neural crest-derived cells. This study sought to
      determine if ADSC express keratocyte-specific phenotypic markers when cultured
      under conditions inducing differentiation of corneal stromal stem cells to
      keratocytes. METHODS: Human subcutaneous adipose tissue was obtained by
      lipoaspiration. ADSC were isolated by collagenase digestion and differential
      centrifugation. Side population cells in ADSC were demonstrated using
      fluorescence-activated cell sorting after staining with Hoechst 33342.
      Differentiation to keratocyte phenotype was induced in fibrin gels or as pellet
      cultures with serum-free or reduced-serum media containing ascorbate. Keratocyte
      specific gene expression was characterized using western blotting, quantitative
      RT-PCR, and immunostaining. RESULTS: ADSC contained a side population and
      exhibited differentiation to adipocytes and chondrocytes indicating adult stem
      cell potential. Culture of ADSC in fibrin gels or as pellets in reduced-serum
      medium with ascorbate and insulin induced expression of keratocan, keratan
      sulfate, and aldehyde dehydrogenase 3 family, member A1 (ALDH3A1), products
      highly expressed by differentiated keratocytes. Expression of differentiation
      markers was quantitatively similar to corneal stromal stem cells and occurred in
      both serum-free and serum containing media. CONCLUSIONS: ADSC cultured under
      keratocyte-differentiation conditions express corneal-specific matrix components.
      Expression of these unique keratocyte products suggests that ADSC can adopt a
      keratocyte phenotype and therefore have potential for use in corneal cell therapy
      and tissue engineering.

PMID- 21179235
TI  - Advanced glycation end products of bovine serum albumin-induced endothelial-to
      mesenchymal transition in cultured human and monkey endothelial cells via protein
      kinase B signaling cascades.
AB  - PURPOSE: Advanced glycation end products of BSA (AGE-BSA) participate in the
      pathogenesis of diabetic vascular disease. However, the role of AGE-BSA in
      diabetic retinopathy, especially in retinal neovascularization, remains
      incomplete. This study aimed to determine the contributions of AGE-BSA in the
      endothelial-to-mesenchymal transition (EnMT) of cultured human and monkey
      endothelial cell lines and the mechanism that may be related with the transition.
      METHODS: Monkey choroid-retinal endothelial cells (RF/6A) and human umbilical
      vein endothelial cells (HUVEC) were cultured in Dulbecco's modified Eagle's
      Medium (DMEM) and Ham's F12 medium containing 200 mg/l AGE-BSA. The expression of
      VE-cadherin, beta-catenin, vimentin, N-cadherin, and protein kinase B (AKT2) was
      observed by immunocytochemistry and flow cytometry. Cell motility was determined
      by migration assays; the endothelial function of the formatting tube was measured
      by tube formation assays, while the change in the polarity was measured using
      resistance instruments. RESULTS: The characteristics of EnMT included loss of
      endothelial markers of VE-cadherin and beta-catenin, which were replaced by
      mesenchymal markers of vimentin and N-cadherin, enhanced migration and tube
      formation, and diminished polarity. AGE-BSA contributed to upregulation of the
      protein expression of VE-cadherin and beta-catenin and downregulation of protein
      expression of vimentin and N-cadherin, leading to enhanced migration and tube
      formation and diminished polarity. During this process, expression of AKT2 was
      upregulated. CONCLUSIONS: AGE-BSA can induce EnMT of cultured human and monkey
      endothelial cells. The signal pathway involving AKT2 may play a role in this
      process.

PMID- 21179236
TI  - Analysis of candidate genes for macular telangiectasia type 2.
AB  - PURPOSE: To find the gene(s) responsible for macular telangiectasia type 2
      (MacTel) by a candidate-gene screening approach. METHODS: Candidate genes were
      selected based on the following criteria: those known to cause or be associated
      with diseases with phenotypes similar to MacTel, genes with known function in the
      retinal vasculature or macular pigment transport, genes that emerged from
      expression microarray data from mouse models designed to mimic MacTel phenotype
      characteristics, and genes expressed in the retina that are also related to
      diabetes or hypertension, which have increased prevalence in MacTel patients.
      Probands from eight families with at least two affected individuals were screened
      by direct sequencing of 27 candidate genes. Identified nonsynonymous variants
      were analyzed to determine whether they co-segregate with the disease in
      families. Allele frequencies were determined by TaqMan analysis of the large
      MacTel and control cohorts. RESULTS: We identified 23 nonsynonymous variants in
      27 candidate genes in at least one proband. Of these, eight were known single
      nucleotide polymorphisms (SNPs) with allele frequencies of >0.05; these variants
      were excluded from further analyses. Three previously unidentified missense
      variants, three missense variants with reported disease association, and five
      rare variants were analyzed for segregation and/or allele frequencies. No variant
      fulfilled the criteria of being causal for MacTel. A missense mutation,
      p.Pro33Ser in frizzled homolog (Drosophila) 4 (FZD4), previously suggested as a
      disease-causing variant in familial exudative vitreoretinopathy, was determined
      to be a rare benign polymorphism. CONCLUSIONS: We have ruled out the exons and
      flanking intronic regions in 27 candidate genes as harboring causal mutations for
      MacTel.

PMID- 21179237
TI  - The expression of Wnt2b in the optic cup lip requires a border between the
      pigmented and nonpigmented epithelium.
AB  - PURPOSE: Wnt2b is normally expressed at the optic cup lip and is implicated in
      ciliary body induction. The lens has often been considered an organizer for the
      anterior eye, but recent studies demonstrate that the anterior cell fates are
      correctly specified in the absence of the lens. This study uses Wnt2b as a marker
      to reveal the mechanism behind the specification of the anterior domain of the
      optic cup. METHODS: Developing chick embryos were used as a model system. Eyes
      were microsurgically manipulated to assess the role of the lens in the
      development of the anterior optic cup. Eyes were molecularly manipulated, using
      fibroblast growth factor expressing replication-incompetent retrovirus,
      introduced into the retinal pigmented epithelium (RPE) domain. Ectopic fibroblast
      growth factor transformed the RPE into nonpigmented epithelium (NPE; ciliary
      body). As the virus does not spread, discrete borders between RPE and NPE were
      experimentally created. Wnt2b expression was assessed after surgical and
      molecular manipulation. RESULTS: Contrary to expectations, we found that the lens
      is not able to induce Wnt2b expression in optic cup tissue: When the optic cup
      lip is experimentally misspecified such that it no longer contains the
      juxtaposition of pigmented and nonpigmented tissue, Wnt2b is not expressed. In
      addition, if the prelens ectoderm is removed from the optic vesicle before
      morphogenesis, the resulting lensless optic cup expresses Wnt2b even though it
      was not in contact with lens tissue. We also show that ectopic lenses do not
      induce Wnt2b in optic cup tissue. The ciliary body/anterior eye domain is
      specified at the border of RPE and the NPE of the ciliary body. During
      development, this border is normally found at the optic cup lip. We can
      manipulate tissue specification using retroviral-mediated gene transfer, and
      create ectopic borders between nonpigmented and pigmented tissue. At such
      borders, Wnt2b is ectopically expressed in the absence of lens contact. Finally,
      we describe a role for the lens in maintenance of Wnt2b expression and
      demonstrate support for this in two ways: First, we show that if the lens is
      removed from the formed optic cup, endogenous Wnt2b expression is specifically
      lost from the optic cup lip; and second, we show that while ectopic Wnt2b
      expression is initially found in the majority of ectopic borders, as eye
      development proceeds ectopic expression is maintained only in those borders that
      are close to the lens. CONCLUSIONS: Taken together, the results provide support
      for a model in which the anterior optic cup domain, as described in part by Wnt2b
      expression, is specified through the elaboration of a border within the optic
      neuroepithelium rather than through interactions with the surrounding
      environment.

PMID- 21179238
TI  - Subepithelial corneal fibrosis partially due to epithelial-mesenchymal transition
      of ocular surface epithelium.
AB  - PURPOSE: To determine whether epithelial-mesenchymal transition is involved in
      the development of corneal subepithelial fibrosis (pannus). METHODS: Frozen
      samples of pannus tissue removed from human corneas with a diagnosis of total
      limbal stem cell deficiency were characterized by immunostaining for both
      epithelial and mesenchymal markers. We selected transformation-related protein 63
      (p63) and pancytokeratin as epithelial markers and vimentin and alpha-smooth
      muscle actin (alpha-SMA) as mesenchymal markers. Immunostaining for beta-catenin
      and E-cadherin was performed to determine wingless-Int (Wnt)-pathway activation.
      RT-PCR analysis was also performed on epithelial tissue obtained from pannus
      samples after dispase digestion. RESULTS: Immunohistochemistry revealed strong
      nuclear expression of p63 and weak intercellular expression of E-cadherin in
      epithelial basal cells of pannus tissue. Furthermore, translocation of beta
      catenin from intercellular junctions to the nucleus and cytoplasm was also
      observed. Double-positive cells for both p63 and alpha-SMA were observed in the
      subepithelial stroma of pannus tissue, which was supported by RT-PCR and cytospin
      analysis. CONCLUSIONS: Epithelial-mesenchymal transition may be partially
      involved in the development of subepithelial corneal fibrosis due to total limbal
      stem cell deficiency.

PMID- 21179239
TI  - Mapping of a new locus associated with autosomal recessive congenital cataract to
      chromosome 3q.
AB  - PURPOSE: To localize the disease interval for autosomal recessive congenital
      cataracts in a consanguineous Pakistani family. METHODS: All affected individuals
      underwent detailed ophthalmologic examination. Blood samples were collected and
      genomic DNA was extracted. A genome-wide scan was performed with fluorescently
      labeled microsatellite markers on genomic DNA from affected and unaffected family
      members and logarithm of odds (LOD) scores were calculated. RESULTS: Clinical
      records and ophthalmological examinations suggested that affected individuals
      have bilateral congenital cataracts. Genome-wide linkage analysis localized the
      critical interval to chromosome 3q with a maximum LOD score of 3.87 at theta=0;
      with marker D3S3609. Haplotype analyses refined the critical interval to a 23.39
      cM (18.01 Mb) interval on chromosome 3q, flanked by D3S1614 proximally and
      D3S1262, distally. CONCLUSIONS: Here, we report a new locus for autosomal
      recessive congenital cataract localized to chromosome 3q in a consanguineous
      Pakistani family.

PMID- 21179240
TI  - Overexpressed or intraperitoneally injected human transferrin prevents
      photoreceptor degeneration in rd10 mice.
AB  - PURPOSE: Retinal degeneration has been associated with iron accumulation in age
      related macular degeneration (AMD), and in several rodent models that had one or
      several iron regulating protein impairments. We investigated the iron
      concentration and the protective role of human transferrin (hTf) in rd10 mice, a
      model of retinal degeneration. METHODS: The proton-induced X-ray emission (PIXE)
      method was used to quantify iron in rd10 mice 2, 3, and 4 weeks after birth. We
      generated mice with the beta-phosphodiesterase mutation and hTf expression by
      crossbreeding rd10 mice with TghTf mice (rd10/hTf mice). The photoreceptor loss
      and apoptosis were evaluated by terminal deoxynucleotidyl transferase dUTP nick
      end labeling in 3-week-old rd10/hTf mice and compared with 3-week-old rd10 mice.
      The neuroprotective effect of hTf was analyzed in 5-day-old rd10 mice treated by
      intraperitoneal administration with hTf for up to 25 days. The retinal hTf
      concentrations and the thickness of the outer nuclear layer were quantified in
      all treated mice at 25 days postnatally. RESULTS: PIXE analysis demonstrated an
      age-dependent iron accumulation in the photoreceptors of rd10 mice. The rd10/hTf
      mice had the rd10 mutation, expressed high levels of hTf, and showed a
      significant decrease in photoreceptor death. In addition, rd10 mice
      intraperitoneally treated with hTf resulted in the retinal presence of hTf and a
      dose-dependent reduction in photoreceptor degeneration. CONCLUSIONS: Our results
      suggest that iron accumulation in the retinas of rd10 mutant mice is associated
      with photoreceptor degeneration. For the first time, the enhanced survival of
      cones and rods in the retina of this model has been demonstrated through
      overexpression or systemic administration of hTf. This study highlights the
      therapeutic potential of Tf to inhibit iron-induced photoreceptor cell death
      observed in degenerative diseases such as retinitis pigmentosa and age-related
      macular degeneration.

PMID- 21179241
TI  - Effectiveness of topical caffeine in cataract prevention: studies with galactose
      cataract.
AB  - PURPOSE: The primary objective of the study was to investigate the possible
      inhibition of cataract formation by topical administration of caffeine using the
      galactosemic rat model. It was hypothesized that caffeine will do so by acting as
      scavenger of reactive oxygen species known to be generated under hyperglycemic
      conditions. METHODS: Cataract was induced by feeding young rats a diet containing
      24% galactose for a period of 25 days. A control group of such rats was treated
      with a placebo eye drop preparation containing hydroxy propyl methyl cellulose as
      a wetting agent. In the experimental group, the rats were treated with the above
      preparation mixed with 72 mM caffeine. RESULTS: Administration of caffeine eye
      drops was found to significantly inhibit the onset as well as the progress of
      cataract formation. By day 25 on the galactose diet, all the animals in the
      control group developed advanced white opacity spread over the entire area of the
      lens. In the caffeine group, the formation of such opacity remained strikingly
      inhibited. The lenses remained largely transparent. The transparency data
      paralleled the higher concentration of glutathione maintained by caffeine
      treatment. Its levels in the placebo group were 0.8, 0.5, and 0.4 umoles/g lens
      wt. on days 5, 15, and 25 against a consistent basal control value of ~3 umoles/g
      over the entire period. In the caffeine group, the corresponding values were
      nearly 3 umoles/g till day 15, but decreasing to ~2 umoles/g on day 25. The
      levels were hence significantly higher than in the caffeine untreated group,
      remaining relatively closer to the basal controls. In addition, the compound was
      found effective in inhibiting morphological changes induced by galactose.
      CONCLUSIONS: Micromolar amounts of topical caffeine have been found to be
      significantly effective in inhibiting the formation of galactose cataract,
      strongly suggesting its possible usefulness against diabetic cataracts. The
      effects are attributed to its ability to prevent oxidative stress and consequent
      maintenance of tissue metabolic and transport functions, in addition to
      preventing the induction of apoptosis.

PMID- 21179242
TI  - Light-induced photoreceptor and RPE degeneration involve zinc toxicity and are
      attenuated by pyruvate, nicotinamide, or cyclic light.
AB  - PURPOSE: Light-induced damage can be a problem after surgery or sun exposure.
      Short-duration, intense light causes preferential photoreceptor death in the
      superior central retina of albino mice and rats and serves as a model of
      oxidation-induced neurodegeneration. Previous work on retinal ischemia-induced
      neuronal death suggests the involvement of zinc (Zn(2+)) toxicity in the death
      and collapse of many retinal cell layers and demonstrates the protective efficacy
      of pyruvate. Retinal pigment epithelial (RPE) cells were shown to be sensitive to
      oxidative stress, and zinc, causing loss of nicotinamide adenine dinucleotide
      (NAD+) and adenine triphosphate (ATP), which was prevented by pyruvate and
      nicotinamide. We previously showed similar results in cortical neurons exposed to
      oxidative stress or Zn(2+). In vivo, Zn(2+) is normally present in the inner and
      outer segments (associated with rhodopsin), Bruch's membrane and sclera
      (elastin), RPE, and the outer plexiform layer of the eye (synaptic). In this
      study, we examine the role of Zn(2+) in oxidative stress and light-induced damage
      in vitro and in vivo. METHODS: We modeled retinal toxicity in cell-culture lines
      derived from retinal tissue: Muller and human retinal pigment epithelial (ARPE
      19) cells and a cone photoreceptor-derived line (661W). These cultures were
      exposed to Zn(2+) and OS, and the therapeutic efficacy of pyruvate, nicotinamide,
      and NAD(+) was determined. Sprague Dawley albino rats were exposed to 18 kLux of
      white fluorescent light for 1-4 h in the presence and absence of pyruvate,
      nicotinamide, lactate, and cyclic light. The intracellular free zinc
      concentration ([Zn(2+)](i)) and cell damage were assessed 0.5 and 7 days later,
      respectively. RESULTS: We show that Zn(2+) and oxidative stress results in
      increased [Zn(2+)](i) and that Zn(2+) therapeutic compounds (pyruvate,
      nicotinamide, and NAD(+)) and inhibitors of previously implicated pathways
      (sirtuin) are efficacious in vitro. Exposure to 18 kLux of cool white fluorescent
      light for 1 h induced a large increase in Zn(2+) staining 4-14 h later,
      particularly in the superior outer nuclear layer and RPE of dark-maintained
      Sprague Dawley albino rats; 4 h of light was required to induce similar damage in
      cyclic light-maintained rats. Photoreceptors and RPE cells died in untreated
      animals at 3-7 days. However, nicotinamide and pyruvate (intraperitoneal), but
      not lactate, attenuated this death in treated animals, as measured using optical
      coherence tomography and confirmed by counting photoreceptor nuclei. CONCLUSIONS:
      Zn(2+) plays a role in this injury, as suggested by the increased Zn(2+) staining
      and the efficacy of Zn(2+) therapeutics. These results suggest that cyclic light
      maintenance, Zn(2+) chelation, pyruvate, and nicotinamide promote RPE and
      photoreceptor survival after injury and could be effective for various forms of
      retinal neurodegeneration. These results could have immediate clinical
      applications in surgery- or sun exposure- induced light damage to the retina.

PMID- 21179243
TI  - A novel nonsense mutation in the NDP gene in a Chinese family with Norrie
      disease.
AB  - PURPOSE: Norrie disease (ND), a rare X-linked recessive disorder, is
      characterized by congenital blindness and, occasionally, mental retardation and
      hearing loss. ND is caused by the Norrie Disease Protein gene (NDP), which codes
      for norrin, a cysteine-rich protein involved in ocular vascular development.
      Here, we report a novel mutation of NDP that was identified in a Chinese family
      in which three members displayed typical ND symptoms and other complex
      phenotypes, such as cerebellar atrophy, motor disorders, and mental disorders.
      METHODS: We conducted an extensive clinical examination of the proband and
      performed a computed tomography (CT) scan of his brain. Additionally, we
      performed ophthalmic examinations, haplotype analyses, and NDP DNA sequencing for
      26 individuals from the proband's extended family. RESULTS: The proband's
      computed tomography scan, in which the fifth ventricle could be observed,
      indicated cerebellar atrophy. Genome scans and haplotype analyses traced the
      disease to chromosome Xp21.1-p11.22. Mutation screening of the NDP gene
      identified a novel nonsense mutation, c.343C>T, in this region. CONCLUSIONS:
      Although recent research has shown that multiple different mutations can be
      responsible for the ND phenotype, additional research is needed to understand the
      mechanism responsible for the diverse phenotypes caused by mutations in the NDP
      gene.

PMID- 21179244
TI  - The PluriNetWork: an electronic representation of the network underlying
      pluripotency in mouse, and its applications.
AB  - BACKGROUND: Analysis of the mechanisms underlying pluripotency and reprogramming
      would benefit substantially from easy access to an electronic network of genes,
      proteins and mechanisms. Moreover, interpreting gene expression data needs to
      move beyond just the identification of the up-/downregulation of key genes and of
      overrepresented processes and pathways, towards clarifying the essential effects
      of the experiment in molecular terms. METHODOLOGY/PRINCIPAL FINDINGS: We have
      assembled a network of 574 molecular interactions, stimulations and inhibitions,
      based on a collection of research data from 177 publications until June 2010,
      involving 274 mouse genes/proteins, all in a standard electronic format, enabling
      analyses by readily available software such as Cytoscape and its plugins. The
      network includes the core circuit of Oct4 (Pou5f1), Sox2 and Nanog, its periphery
      (such as Stat3, Klf4, Esrrb, and c-Myc), connections to upstream signaling
      pathways (such as Activin, WNT, FGF, BMP, Insulin, Notch and LIF), and epigenetic
      regulators as well as some other relevant genes/proteins, such as proteins
      involved in nuclear import/export. We describe the general properties of the
      network, as well as a Gene Ontology analysis of the genes included. We use
      several expression data sets to condense the network to a set of network links
      that are affected in the course of an experiment, yielding hypotheses about the
      underlying mechanisms. CONCLUSIONS/SIGNIFICANCE: We have initiated an electronic
      data repository that will be useful to understand pluripotency and to facilitate
      the interpretation of high-throughput data. To keep up with the growth of
      knowledge on the fundamental processes of pluripotency and reprogramming, we
      suggest to combine Wiki and social networking software towards a community
      curation system that is easy to use and flexible, and tailored to provide a
      benefit for the scientist, and to improve communication and exchange of research
      results. A PluriNetWork tutorial is available at http://www.ibima.med.uni
      rostock.de/IBIMA/PluriNetWork/.

PMID- 21179245
TI  - TIA-1 cytotoxic granule-associated RNA binding protein improves the prognostic
      performance of CD8 in mismatch repair-proficient colorectal cancer.
AB  - BACKGROUND: Evidence suggests a confounding effect of mismatch repair (MMR)
      status on immune response in colorectal cancer. The identification of innate and
      adaptive immune cells, that can complement the established prognostic effect of
      CD8 in MMR-proficient colorectal cancers patients, representing 85% of all cases,
      has not been performed. METHODOLOGY/PRINCIPAL FINDINGS: Colorectal cancers from a
      test (n=1197) and external validation (n=209) cohort of MMR-proficient colorectal
      cancers were mounted onto single and multiple punch tissue microarrays.
      Immunohistochemical quantification (score 0-3) was performed for CD3, CD4, CD8,
      CD45RO, CD68, CD163, FoxP3, GranzymeB, iNOS, mast cell tryptase, MUM1, PD1 and
      TIA-1 tumor-infiltrating (TILs) reactive cells. Coexpression experiments on fresh
      colorectal cancer specimens using specific cell population markers were
      performed. In the test group, higher numbers of CD3+ (p<0.001), CD4+ (p=0.029),
      CD8+ (p<0.001), CD45RO+ (p=0.048), FoxP3+ (p<0.001), GranzymeB+ (p<0.001), iNOS+
      (p=0.035), MUM1+ (p=0.014), PD1+ (p=0.034) and TIA-1+ TILs (p<0.001) were linked
      to favourable outcome. Adjusting for age, gender, TNM stage and post-operative
      therapy, higher CD8+ (p<0.001; HR (95%CI): 0.66 (0.64-0.68)) and TIA-1+ (p<0.001;
      HR (95%CI): 0.56 (0.5-0.6)) were independent prognostic factors. Moreover, among
      patients with CD8+ infiltrates, TIA-1 further stratified 355 (35.6%) patients
      into prognostic subgroups (p<0.001; HR (95%CI): 0.89 (95%CI: 0.8-0.9)). Results
      were confirmed on the validation cohort (p=0.006). TIA-1+ cells were mostly CD8+
      (57%), but also stained for TCRgammadelta (22%), CD66b (13%) and only rarely for
      CD4+, macrophage and NK cell markers. CONCLUSIONS: TIA-1 adds prognostic
      information to TNM stage and adjuvant therapy in MMR-proficient colorectal cancer
      patients. The prognostic effect of CD8+ TILs is confounded by the presence of TIA
      1+ which translates into improved risk stratification for approximately 35% of
      all patients with MMR-proficient colorectal cancers.

PMID- 21179246
TI  - Toxoplasma gondii lysine acetyltransferase GCN5-A functions in the cellular
      response to alkaline stress and expression of cyst genes.
AB  - Parasitic protozoa such as the apicomplexan Toxoplasma gondii progress through
      their life cycle in response to stimuli in the environment or host organism. Very
      little is known about how proliferating tachyzoites reprogram their expressed
      genome in response to stresses that prompt development into latent bradyzoite
      cysts. We have previously linked histone acetylation with the expression of stage
      specific genes, but the factors involved remain to be determined. We sought to
      determine if GCN5, which operates as a transcriptional co-activator by virtue of
      its histone acetyltransferase (HAT) activity, contributed to stress-induced
      changes in gene expression in Toxoplasma. In contrast to other lower eukaryotes,
      Toxoplasma has duplicated its GCN5 lysine acetyltransferase (KAT). Disruption of
      the gene encoding for TgGCN5-A in type I RH strain did not produce a severe
      phenotype under normal culture conditions, but here we show that the TgGCN5-A
      null mutant is deficient in responding to alkaline pH, a common stress used to
      induce bradyzoite differentiation in vitro. We performed a genome-wide analysis
      of the Toxoplasma transcriptional response to alkaline pH stress, finding that
      parasites deleted for TgGCN5-A fail to up-regulate 74% of the stress response
      genes that are induced 2-fold or more in wild-type. Using chromatin
      immunoprecipitation, we verify an enrichment of TgGCN5-A at the upstream regions
      of genes activated by alkaline pH exposure. The TgGCN5-A knockout is also
      incapable of up-regulating key marker genes expressed during development of the
      latent cyst form, and is impaired in its ability to recover from alkaline stress.
      Complementation of the TgGCN5-A knockout restores the expression of these stress
      induced genes and reverses the stress recovery defect. These results establish
      TgGCN5-A as a major contributor to the alkaline stress response in RH strain
      Toxoplasma.

PMID- 21179247
TI  - Remote library access for pharmacy preceptors.
AB  - OBJECTIVE: To institute and evaluate the response to a program providing access
      to electronic library resources for pharmacy preceptors. DESIGN: The pharmacy
      experiential office and the library collaborated using existing programs and
      technology to provide and market secure remote access for preceptors. ASSESSMENT:
      Preceptor participation was tracked in the experiential office, and response to
      the program was assessed using an online survey instrument that included
      questions about use of and preference for specific library resources. Three
      hundred thirty-four adjunct faculty members registered, representing 34% of all
      preceptors with active e-mail accounts. CONCLUSION: Preceptor participation in
      the program exceeded expectations. Some minor flaws in the logistics of
      delivering the service were identified and remedied.

PMID- 21179248
TI  - Active-learning strategies to develop health literacy knowledge and skills.
AB  - OBJECTIVE: To implement active-learning exercises in a required pharmacy course
      and assess their impact on students' knowledge and confidence in identifying and
      communicating with patients with low health literacy, as part of a required
      course in cultural competency, health literacy, and health beliefs. DESIGN:
      Active-learning activities including administering health literacy assessments,
      identifying informal signs of low health literacy, conducting mock patient
      counseling sessions, rating the readability of drug information, analyzing
      information in drug advertisements, and writing patient education materials were
      incorporated into the 6-sesssion health literacy portion of the course.
      ASSESSMENT: A pretest and posttest showed that students' knowledge of health
      literacy increased, and a retrospective pretest found improvement in students'
      confidence in their ability to care for patients with low health literacy. In
      class discussions provided informal evidence that students gained new knowledge
      from the active-learning activities. CONCLUSION: The addition of active-learning
      activities was effective in teaching health literacy concepts to pharmacy
      students.

PMID- 21179249
TI  - The impact of student-faculty ratio on pharmacy faculty scholarship.
AB  - OBJECTIVE: To determine the relationship and impact of student-faculty ratio on
      scholarship of pharmacy faculty members. METHODS: The number and rank of faculty
      members, pharmacy program characteristics, and faculty productivity data were
      collected to determine the impact of student-faculty ratio on faculty
      scholarship. RESULTS: Faculty scholarship was not predicted by student-faculty
      ratio. Factors impacting positively on faculty productivity included National
      Institutes of Health funding; presence of clinical associate professors,
      instructors, and lecturers; and programs located in public universities.
      CONCLUSIONS: Faculty productivity is not related to the student-faculty ratio,
      wherein more faculty members and fewer students equates to increased scholarship.
      However, public universities may have different infrastructures which are
      associated with greater academic productivity compared to private institutions.
      Additionally, utilizing instructors and clinical or nontenure-track faculty
      members can significantly increase scholarship among faculty members.

PMID- 21179250
TI  - Pharmacy students provide care comparable to pharmacists in an outpatient
      anticoagulation setting.
AB  - OBJECTIVE: To evaluate whether student participation in ambulatory clinics
      influenced the percentage of therapeutic international normalized ratio (INR)
      results among patients on chronic warfarin therapy. METHODS: Medical records in
      outpatient anticoagulation clinics managed by pharmacists under physician
      protocol were reviewed retrospectively in 2 university-affiliated clinics in
      Amarillo and Lubbock, TX. Pharmacy student activities included patient
      interviews, vital sign measurements, fingersticks, counseling, and documentation.
      Patient visits were conducted by a precepted pharmacy student or a pharmacist
      without a student, and the INR was measured at the subsequent patient visit.
      RESULTS: Records of 1,958 anticoagulation patient visits were reviewed; 865
      patients were treated by pharmacists, and 1093 were treated by precepted
      students. The follow-up INR was therapeutic for 48.5% of third-year (P3)
      students' patients, 45.6% of fourth-year (P4) students' patients, 51.2% of
      residents' patients, and 44.7% of pharmacists's patients (p = 0.23). Eight
      variables were associated with the follow-up INR (baseline INR, warfarin
      noncompliance, held warfarin doses, a warfarin dosage adjustment, diet change,
      alcohol use, tobacco use, and any medication changes). CONCLUSION: Student
      participation in the patient-care process did not compromise patient care and no
      significant difference in patient outcomes was found between patients in an
      anticoagulation clinic cared for by precepted students and those cared for by
      pharmacists.

PMID- 21179252
TI  - Presenting and evaluating qualitative research.
AB  - The purpose of this paper is to help authors to think about ways to present
      qualitative research papers in the American Journal of Pharmaceutical Education.
      It also discusses methods for reviewers to assess the rigour, quality, and
      usefulness of qualitative research. Examples of different ways to present data
      from interviews, observations, and focus groups are included. The paper concludes
      with guidance for publishing qualitative research and a checklist for authors and
      reviewers.

PMID- 21179251
TI  - Benchmarking in academic pharmacy departments.
AB  - Benchmarking in academic pharmacy, and recommendations for the potential uses of
      benchmarking in academic pharmacy departments are discussed in this paper.
      Benchmarking is the process by which practices, procedures, and performance
      metrics are compared to an established standard or best practice. Many businesses
      and industries use benchmarking to compare processes and outcomes, and ultimately
      plan for improvement. Institutions of higher learning have embraced benchmarking
      practices to facilitate measuring the quality of their educational and research
      programs. Benchmarking is used internally as well to justify the allocation of
      institutional resources or to mediate among competing demands for additional
      program staff or space. Surveying all chairs of academic pharmacy departments to
      explore benchmarking issues such as department size and composition, as well as
      faculty teaching, scholarly, and service productivity, could provide valuable
      information. To date, attempts to gather this data have had limited success. We
      believe this information is potentially important, urge that efforts to gather it
      should be continued, and offer suggestions to achieve full participation.

PMID- 21179253
TI  - Cooperation in pharmacy education in Canada and the United States.
AB  - Although the education of student pharmacists and the practice of pharmacy in
      Canada have many similarities with that in the United States, there also are
      differences. The planning of curricula in pharmacy education is of particular
      importance to the advancement of pharmacy in Canada because of significant
      changes in the scope of practice in several provinces, and in how community
      pharmacy is reimbursed for the services it can, or should, provide. Greater
      dialog between Canadian and American pharmacists has the potential not only to
      impact practice on both sides of the border but also to improve collaborations
      among Canadian and American pharmacy educators. This article provides background
      information and some suggestions on how to build partnerships in pharmacy
      education between Canada and the United States. Consortia-like arrangements have
      some particular promise, as does engaging border-states and provinces in regional
      meetings and other activities. By working together, Canadian and US pharmacy
      educators have the opportunity to implement the best of what each has to offer
      and to devise new and better ways to educate future and existing pharmacists.

PMID- 21179254
TI  - Virtual patients and problem-based learning in advanced therapeutics.
AB  - OBJECTIVE: To enhance student learning of a complex therapeutic concept through
      the incorporation of 2 case-based, active-learning strategies with lecture in a
      required advanced therapeutics course. DESIGN: A virtual patient session using a
      branched-outcome decision-making model and a problem-based learning (PBL)
      practica were developed from the course learning objectives for severe sepsis and
      septic shock. Following lecture of this material, students were required to
      complete the simulation session and attend the PBL. ASSESSMENT: Student learning
      was assessed through review of examination scores, as well as quality and
      accuracy of the pharmaceutical care plan developed as part of the PBL.
      Satisfaction of the teaching format was assessed through a course evaluation
      survey. For questions pertaining to sepsis or septic shock on the final
      examination, the class average was 90%, despite an average of 76% on the
      examination as a whole. Class average for the pharmacuetical care plan was 90%.
      Sixty-three percent of students stated the simulation contributed to their
      learning, and 93% stated the PBL contributed to their learning. CONCLUSION: Using
      a multifaceted teaching approach, combining active- and passive-learning
      strategies, was well received by students and fostered an effective learning
      environment.

PMID- 21179255
TI  - A pharmacy practice laboratory exercise to apply biochemistry concepts.
AB  - OBJECTIVES: To develop exercises that allow pharmacy students to apply
      foundational knowledge discussed in a first-professional year (P1) biochemistry
      course to specific disease states and patient scenarios. DESIGN: A pharmacy
      practice laboratory exercise was developed to accompany a lecture sequence
      pertaining to purine biosynthesis and degradation. The assignment required
      students to fill a prescription, provide patient counseling tips, and answer
      questions pertaining to the disease state, the underlying biochemical problem,
      and the prescribed medication. ASSESSMENT: Students were graded on the accuracy
      with which they filled the prescription, provided patient counseling, and
      answered the questions provided. Overall, students displayed mastery in all of
      these areas. Additionally, students completed a course survey on which they rated
      this exercise favorably, noting that it helped them to integrate basic science
      concepts and pharmacy practice. CONCLUSION: A laboratory exercise provided an
      opportunity for P1 students to apply foundational pharmacy knowledge to a patient
      case and can serve as a template for the design of additional exercises.

PMID- 21179256
TI  - Using facebook within a geriatric pharmacotherapy course.
AB  - OBJECTIVE: To evaluate using an Internet-based social networking site within an
      elective geriatric pharmacotherapy course. DESIGN: Thirty pharmacy students
      enrolled in a geriatric pharmacotherapy elective course were invited to join a
      closed Facebook (Facebook Inc, Palo Alto, CA) group to enhance communication
      among students and faculty members within the course. Creating a discussion board
      was the primary activity in the course. Each week, 3 students were assigned to
      post a healthy aging topic, and other students in the class were expected to post
      their comments and reactions. The healthy aging topics also were discussed during
      class. ASSESSMENT: Students wrote reflections about their experiences using
      Facebook for the activities within this course. A survey instrument also measured
      students' opinions about using Facebook for educational purposes. CONCLUSION:
      Using Facebook allowed students to discuss topics more openly and encouraged
      classroom discussions of healthy aging topics.

PMID- 21179257
TI  - Simulation-based learning about medication management difficulties of low-vision
      patients.
AB  - OBJECTIVE: To implement and evaluate a simulation activity and related
      assignments within a geriatric elective to teach pharmacy students about the
      medication management difficulties experienced by low-vision patients. DESIGN:
      Students wore low-vision simulation goggles while engaging in medication
      management tasks. Students also reflected on their experiences in journals and
      developed modalities to improve low-vision patients' access to prescription
      information. ASSESSMENT: Results of a perception survey indicated that students
      were able to identify and differentiate among various low-vision medication
      management difficulties. Students' reflections suggested that they recognized the
      challenges encountered by low-vision patients. All patient assistance project
      submissions were suitable for the targeted populations and medication management
      difficulties. Peer review and student feedback of the activities were favorable.
      CONCLUSION: Through this low-vision goggle simulation exercise and other
      activities, students were able to identify the medication management difficulties
      encountered by low-vision patients and propose solutions to their drug
      information access problems.

PMID- 21179258
TI  - Active-learning exercises to teach drug-receptor interactions in a medicinal
      chemistry course.
AB  - OBJECTIVE: To incorporate structural biology, enzyme kinetics, and visualization
      of protein structures in a medicinal chemistry course to teach fundamental
      concepts of drug design and principles of drug action. DESIGN: Pedagogy for
      active learning was incorporated via hands-on experience with visualization
      software for drug-receptor interactions and concurrent laboratory sessions.
      Learning methods included use of clicker technology, in-class assignments, and
      analogies. ASSESSMENT: Quizzes and tests that included multiple-choice and open
      ended items based on Bloom's taxonomy were used to assess learning. Student
      feedback, classroom exercises, and tests were used to assess teaching methods and
      effectiveness in meeting learning outcomes. CONCLUSION: The addition of active
      learning activities increased students' understanding of fundamental medicinal
      chemistry concepts such as ionization state of molecules, enzyme kinetics, and
      the significance of protein structure in drug design.

PMID- 21179259
TI  - Objective structured clinical examinations in doctor of pharmacy programs in the
      United States.
AB  - OBJECTIVES: To describe current objective structured clinical examination (OSCE)
      practices in doctor of pharmacy (PharmD) programs in the United States. METHODS:
      Structured interviews were conducted with PharmD faculty members between
      September 2008 and May 2010 to collect information about awareness of and
      interest in OSCE, current OSCE practices, and barriers to OSCEs. RESULTS: Of 108
      US colleges and schools of pharmacy identified, interviews were completed for a
      representative sample of 88 programs (81.5% participation rate). Thirty-two
      pharmacy programs reported using OSCEs; however, practices within these programs
      varied. Eleven of the programs consistently administered examinations of 3 or
      more stations, required all students to complete the same scenario(s), and had
      processes in place to ensure consistency of standardized patients' role
      portrayal. Of the 55 programs not using OSCEs, approximately half were interested
      in using the technique. Common barriers to OSCE implementation or expansion were
      cost and faculty members' workloads. CONCLUSIONS: There is wide interest in using
      OSCEs within pharmacy education. However, few colleges and schools of pharmacy
      conduct OSCEs in an optimal manner, and most do not adhere to best practices in
      OSCE construction and administration.

PMID- 21179260
TI  - Theoretical and conceptual framework for a high school pathways to pharmacy
      program.
AB  - OBJECTIVES: To determine whether participation in the University of Illinois at
      Chicago College of Pharmacy (UIC-COP) Pathways to Pharmacy, an early urban
      pipeline program, motivated underrepresented minority students to pursue a
      prepharmacy curriculum in college and choose pharmacy as a career. METHODS: Over
      a 4-year period, underrepresented minority high school students participated in a
      comprehensive 6-week program that included 3 weeks of prepharmacy curriculum and
      intensive socialization and 3 weeks working as a pharmacy technician in a chain
      pharmacy. The High School Survey of Student Engagement (HSSSE) was administered 3
      times to 120 program participants from 2005-2008, with 4 open-ended questions
      added to the pretest, 3 open-ended questions added to the test administered at
      the midpoint of the program, and 7 open-ended questions added to the posttest.
      RESULTS: After completing the program, 88 (75%) of the 120 students enrolled in
      the college's prepharmacy curriculum and planned to pursue a career in pharmacy,
      10 (8%) were not interested in pursuing a career in pharmacy, and 20 (17%) were
      undecided, compared to the pretest data which showed that 40 (33%) were
      interested in a career in pharmacy, and 80 (67%) were undecided (p < 0.0001).
      CONCLUSIONS: Participation in a Pathways to Pharmacy program grounded in both a
      theoretical and conceptual socialization model framework increased the number of
      underrepresented minority students in the pipeline to pharmacy schools.

PMID- 21179261
TI  - Cultural competence knowledge and confidence after classroom activities.
AB  - OBJECTIVES: To determine change in cultural competency knowledge and perceived
      confidence of second-year pharmacy students to deliver culturally competent care
      after completing a required cultural competency curriculum. DESIGN: Cultural
      competence material was covered in the second-year PharmD curriculum through
      lectures, laboratories, and an experiential/out-of-class assignment. ASSESSMENT:
      Eighty-five second-year (P2) pharmacy students completed a survey which assessed
      influence of classroom activities related to cultural competence. Mean values for
      knowledge and perceived confidence were significantly higher for posttest
      compared to pretest (p < 0.01), after cultural competency activities. Focus
      groups were used to solicit students' opinions on instructional effectiveness,
      relevance of activities, and areas for enhancement. CONCLUSION: The cultural
      competency curriculum increased pharmacy students' awareness of and confidence in
      addressing cultural diversity issues that affect pharmaceutical care delivery.

PMID- 21179262
TI  - Use of laptops and other technology in the classroom.

PMID- 21179263
TI  - Why certain types of technology have been "banned".

PMID- 21179265
TI  - Including motivational interviewing skills in the PharmD curriculum.

PMID- 21179266
TI  - Encouraging the development of emotional intelligence in pharmacy schools.

PMID- 21179267
TI  - Preprofessional curriculum: is it time for another look?

PMID- 21179268
TI  - Bulimic learning.

PMID- 21179269
TI  - Benchmarking for quality improvement.

PMID- 21179270
TI  - The role of photodynamic therapy for hilar cholangiocarcinoma.
AB  - The prognosis for hilar cholangiocarcinoma is limited by tumor spread along the
      biliary tree leading to refractory obstructive cholestasis, cholangitis, and
      liver failure. Palliation with biliary endoprostheses results in median survival
      times of 4-6 months for advanced bile duct cancer. Photodynamic therapy (PDT) is
      a local photochemical tumor treatment consisting of a photosensitizing agent
      combined with laser irradiation of a distinct wavelength. Tumor ablation with PDT
      combined with biliary stenting reduces cholestasis and significantly improves
      median survival time. However, the treatment is not widely available, and the
      photosensitizers used for PDT cause prolonged photosensitivity. Optimum control
      of tumor spread along the bile ducts and control of cholestasis and cholangitis
      will prolong survival in one to two thirds of patients, and renders them suitable
      for other antitumor therapies.

PMID- 21179271
TI  - Effect of statin on the reference segments after bare-metal stent implantation.

PMID- 21179272
TI  - Usual dose of simvastatin does not inhibit plaque progression and lumen loss at
      the peri-stent reference segments after bare-metal stent implantation: a serial
      intravascular ultrasound analysis.
AB  - BACKGROUND/AIMS: The aim of this study was to assess the effects of a usual dose
      of simvastatin (20 mg/day) on plaque regression and vascular remodeling at the
      peri-stent reference segments after bare-metal stent implantation. METHODS: We
      retrospectively investigated serial intravascular ultrasound (IVUS) findings in
      380 peri-stent reference segments (184 proximal and 196 distal to the stent) in
      196 patients (simvastatin group, n = 132 vs. non-statin group, n = 64).
      Quantitative volumetric IVUS analysis was performed in 5-mm vessel segments
      proximal and distal to the stent. RESULTS: IVUS follow-up was performed at a mean
      of 9.4 months after stenting (range, 5 to 19 months). No significant differences
      were observed in the changes in mean plaque plus media (P&M) area, mean lumen
      area, and mean external elastic membrane (EEM) area from post-stenting to follow
      up at both proximal and distal edges between the simvastatin and non-statin
      group. Although lumen loss within the first 3 mm from each stent edge was
      primarily due to an increase in P&M area rather than a change in EEM area, and
      lumen loss beyond 3 mm from each stent edge was due to a combination of increased
      P&M area and decreased EEM area, no significant differences in changes were
      observed in P&M, EEM, and lumen area at every 1-mm subsegment between the
      simvastatin and non-statin group. CONCLUSIONS: A usual dose of simvastatin does
      not inhibit plaque progression and lumen loss and does not affect vascular
      remodeling in peri-stent reference segments in patients undergoing bare-metal
      stent implantation.

PMID- 21179273
TI  - Increased expression of cyclooxygenase-2 is associated with the progression to
      cirrhosis.
AB  - BACKGROUND/AIMS: To investigate the degree of cyclooxygenase-2 (COX-2) protein
      expression in chronic hepatitis and cirrhosis. METHODS: COX-2 protein expression
      was evaluated in 43 cases of chronic hepatitis and 24 cases of cirrhosis using
      immunohistochemical techniques. The COX-2 immunohistochemical staining score was
      assessed using the scoring systems of Pazirandeh et al and Qiu et al. and each
      scoring system was based on a sum of the parameters of staining intensity and
      distribution. RESULTS: The mean COX-2 expression scores in chronic hepatitis and
      cirrhosis were 2.5 +/- 1.3 vs. 3.3 +/- 1.1 (p = 0.008), and 3.2 +/- 2.0 vs. 4.5
      +/- 1.7 (p = 0.006), respectively, based on the Pazirandeh et al. and Qiu et al.
      scoring systems. The percentage samples of high COX-2 expression score (4 to 5)
      in chronic hepatitis and cirrhosis were 16.3% vs. 45.8% (p = 0.022), and 23.3%
      vs. 50% (p = 0.021), respectively, based on the two scoring systems. The mean COX
      2 expression scores based on the severity of hepatic fibrosis scored using
      Ishak's modified staging system (fibrosis score 0 to 3 vs. 4 to 6) were 2.4 +/-
      1.3 vs. 3.2 +/- 1.1 (p = 0.009), and 3.1 +/- 2.0 vs. 4.3 +/- 1.8 (p = 0.009),
      respectively, based on the two scoring systems. CONCLUSIONS: COX-2 expression was
      significantly higher in liver cirrhosis group than in chronic hepatitis. COX-2
      expression scores according to Ishak's staging was significantly higher in the
      advanced fibrosis group. COX-2 may play a role in the progression of hepatic
      fibrosis.

PMID- 21179274
TI  - Efficacy of initial treatment with clevudine in naive patients with chronic
      hepatitis B.
AB  - BACKGROUND/AIMS: Clevudine, a pyrimidine nucleoside analogue, has potent
      antiviral effects in patients with chronic viral hepatitis B (CHB). We report the
      efficacy of initial treatment with clevudine in naive patients with CHB living in
      Daejeon and Chungcheong Province, South Korea. METHODS: One hundred five adults
      with CHB were administered 30 mg of clevudine per day for an average of 51 weeks.
      We evaluated viral markers and liver biochemistry retrospectively every 3 months.
      RESULTS: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and
      hepatitis B virus (HBV) DNA before the treatment were 184 +/- 188 IU/L, 150 +/-
      138 IU/L, and 7.1 +/- 1.2 log copies/mL, respectively. Undetectable rates (< 60
      IU/mL) of DNA were 36.2%, 68.9%, 83.6%, 76.2%, and 75.8% at 12, 24, 36, 48, and
      60 weeks, respectively. Seroconversion rates were 9.1%, 13.6%, 24.6%, 26.5%, and
      26.1% and ALT normalization rates were 64.5%, 78.1%, 87.9%, 90.0% at 12, 24, 36,
      and 48 weeks, respectively. Six patients (5.7%) had a viral breakthrough.
      CONCLUSIONS: Clevudine is a useful drug in the initial treatment of patients with
      CHB, with a potent antiviral effect and low incidence of viral breakthrough.

PMID- 21179275
TI  - Remodeling of ion channel expression in patients with chronic atrial fibrillation
      and mitral valvular heart disease.
AB  - BACKGROUND/AIMS: Underlying cardiac pathology and atrial fibrillation (AF) affect
      the molecular remodeling of ion channels in the atria. Changes in the expression
      of these molecules have not been demonstrated in Korean patients with mitral
      valvular heart disease. Thus, the purpose of this study was to analyze ion
      channel expression in patients with chronic AF and mitral valvular heart disease.
      METHODS: A total of 17 patients (eight males and nine females; mean age, 57 +/-
      14 years [range, 19 to 77]) undergoing open-heart surgery were included in the
      study. Twelve patients (seven with coronary artery disease and five with aortic
      valvular disease) had sinus rhythm, and five patients (all with mitral valvular
      disease) had chronic, permanent AF. A piece of right atrial appendage tissue (0.5
      g) was obtained during surgery. RT-PCR was used to evaluate the expression of L
      type Ca(2+) channels, ryanodine receptor (RyR2), sarcoplasmic reticular Ca(2+)
      ATPase (SERCA2), gene encoding the rapid component of the delayed rectifier I(kr)
      (HERG), gene encoding calcium-independent transient outward current I(to1)
      (Kv4.3), gene encoding the ultrarapid component of the delayed rectifier I(ku)
      (Kv1.5), K(+) channel-interacting protein 2 (KChIP2), hyperpolarization-activated
      cation channel 2 associated with the pacemaker current I(f) (HCN2), and gene
      encoding Na(+) channel (SCN5A). RESULTS: Reduced L-type Ca(2+) channel, RyR2,
      SERCA2, Kv1.5, and KChIP2 expression and borderline increased HCN2 expression
      were observed in the patients with AF and mitral valvular heart disease. Left
      atrial diameter was negatively correlated with RyR2 and KChIP2 expression.
      Fractional area shortening of the left atrium was positively correlated with RyR2
      and KChIP2 expression. CONCLUSIONS: Alterations in ion channel expression and the
      anatomical substrate may favor the initiation and maintenance of AF in patients
      with mitral valvular heart disease.

PMID- 21179276
TI  - Role of (68)Ga-DOTATOC PET/CT in the evaluation of primary pulmonary carcinoids.
AB  - BACKGROUND/AIMS: Although carcinoid tumors usually have good prognosis, early and
      specific diagnosis is important. Computed tomography and magnetic resonance
      imaging do not provide findings that are specific for carcinoids, and
      somatostatin receptor scintigraphy suffers from low spatial resolution. 18
      Fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG
      PET/CT) has limited sensitivity for carcinoids due to low uptake of the marker. A
      PET/CT system that uses the somatostatin receptor-based PET tracer 1,4,7,10
      tetraazacyclododecane-N(I),N(II),N(III),N(IIII)-tetraacetic acid (D)-Phe(1)
      thy(3)-octreotide ((68)Ga-DOTATOC) has also been used in the evaluation of
      carcinoids, although information regarding its use for the detection of primary
      pulmonary carcinoids is limited. Thus, we investigated the value of (68)Ga
      DOTATOC PET/CT for the diagnosis of primary pulmonary carcinoid tumors. METHODS:
      This was a retrospective analysis of patients with primary pulmonary tumors who
      underwent (68)Ga-DOTATOC PET/CT. All the patients had a histopathologic diagnosis
      of carcinoid. The rate of detection of primary pulmonary carcinoid tumors using
      (68)Ga-DOTATOC PET/CT was assessed. RESULTS: Twenty patients were diagnosed as
      having carcinoid, and 19 tumors showed significant uptake on (68)Ga-DOTATOC
      (detection rate, 95%). The maximal standardized uptake value (SUV(max)) ranged
      from 1.1 to 66, with a median value of 21.6. In one patient, (68)Ga-DOTATOC
      PET/CT revealed additional lesions. CONCLUSIONS: Our results demonstrate that
      (68)Ga-DOTATOC PET/CT is useful in the evaluation of primary pulmonary carcinoids
      and should be included in the diagnostic work-up of these patients.

PMID- 21179277
TI  - Influence of additional post-bronchoscopy visit on patient satisfaction after
      flexible bronchoscopy.
AB  - BACKGROUND/AIMS: Many patients undergoing a flexible bronchoscopy (FB) experience
      anxiety and discomfort during the procedure. We assessed whether an additional
      patient visit after a FB would improve patient satisfaction. METHODS: The study
      patients were randomly assigned to a control and post-visit groups. The
      physicians who were scheduled to perform the FB visited the study patients. The
      control group had one visit before the FB and the post-visit group had a before
      and after FB visit. The post-visit group received additional information and
      support during the second visit. Twenty-four hours after the FB, the participants
      completed questionnaires about discomfort and satisfaction with the procedure.
      RESULTS: The control and post-visit groups included 151 and 153 patients,
      respectively. The post-visit group reported having more information after the FB
      than the control group. The additional post-bronchoscopy visit improved the
      general patient tolerability of the procedure. The willingness to return for
      another FB was not affected by the post-bronchoscopy patient visit. CONCLUSIONS:
      The post-bronchoscopy visit improved patient satisfaction and general
      tolerability to the procedure. Subjective patient tolerability with the FB may be
      improved through a post-bronchoscopy visit by providing more information and
      emotional support to patients.

PMID- 21179278
TI  - Microarray analysis of papillary thyroid cancers in Korean.
AB  - BACKGROUND/AIMS: Papillary thyroid cancer (PTC) is the most common malignancy of
      the thyroid gland. It involves several molecular mechanisms. The BRAF V600E
      mutation has been identified as the most common genetic abnormality in PTC.
      Moreover, it is known to be more prevalent in Korean PTC patients than in
      patients from other countries. We investigated distinct genetic profiles in
      Korean PTC through cDNA microarray analysis. METHODS: Transcriptional profiles of
      five PTC samples and five paired normal thyroid tissue samples were generated
      using cDNA microarrays. The tumors were genotyped for BRAF mutations. The results
      of the cDNA microarray gene expression analysis were confirmed by real-time PCR
      and immunohistochemistry analysis of 35 PTC patients. RESULTS: Four of the five
      patients whose PTC tissues were subjected to microarray analysis were found to
      carry the BRAF V600E mutation. Microarrays analysis of the five PTC tissue
      samples showed the expression of 96 genes to be increased and that of 16 genes
      decreased. Real-time reverse transcription-polymerase chain reaction (RT-PCR)
      confirmed increased expression of SLC34A2, TM7SF4, COMP, KLK7, and KCNJ2 and
      decreased expression of FOXA2, SLC4A4, LYVE-1, and TFCP2L1 in PTC compared with
      normal tissue. Of these genes, TFCP2L1, LYVE-1, and KLK7 were previously
      unidentified in PTC microarray analysis. Notably, Foxa2 activity in PTC was
      reduced, as shown by its cytoplasmic localization, in immunohistochemical
      analyses. CONCLUSIONS: These findings demonstrate both similarities and
      differences between our results and previous reports. In Korean cases of PTC,
      Foxa2 activity was reduced with its cytoplasmic accumulation. Further studies are
      needed to confirm the relationship between FOXA2 and BRAF mutations in Korean
      cases of PTC.

PMID- 21179279
TI  - Clinical significance of observation without repeated radioiodine therapy in
      differentiated thyroid carcinoma patients with positive surveillance whole-body
      scans and negative thyroglobulin.
AB  - BACKGROUND/AIMS: Currently, there is no consensus on the necessity of repeated
      radioiodine therapy (RAI) in patients who show iodine uptake in the thyroid bed
      on a diagnostic whole-body scan (DxWBS) despite undetectable thyroglobulin (Tg)
      levels after remnant ablation. The present study investigated the clinical
      outcomes of scan-positive, Tg-negative patients (WBS+Tg-) who did or did not
      receive additional RAI. METHODS: We retrospectively reviewed 389 differentiated
      thyroid carcinoma patients who underwent a total thyroidectomy and received high
      dose RAI from January 2003 through December 2005. The patients were classified
      according to surveillance DxWBS findings and TSH-stimulated Tg levels 6 to 12
      months after the initial RAI. RESULTS: Forty-four of the 389 patients (11.3%)
      showed thyroid bed uptake on a DxWBS despite negative Tg levels (WBS+Tg-). There
      was no difference in clinical and pathological parameters between WBS+Tg- and WBS
      Tg- patients, except for an increased frequency of thyroiditis in the WBS+Tg-
      group. Among the 44 WBS+Tg- patients, 27 subjects were treated with additional
      RAI; 25 subjects showed no uptake in subsequent DxWBS. Two patients were
      evaluated only by ultrasonography (US) and displayed no persistent/recurrent
      disease. The other 17 patients received no further RAI; Eight patients and two
      patients showed no uptake and persistent uptake, respectively, on subsequent
      DxWBS. Six patients presented negative subsequent US findings, and one was lost
      to follow-up. Over the course of 53.2 +/- 10.1 months, recurrence/persistence was
      suspicious in two patients in the treatment group. CONCLUSIONS: There were no
      remarkable differences in clinical outcomes between observation and treatment
      groups of WBS+Tg- patients. Observation without repeated RAI may be an
      alternative management option for WBS+Tg- patients.

PMID- 21179280
TI  - Serum globotriaosylceramide assay as a screening test for fabry disease in
      patients with ESRD on maintenance dialysis in Korea.
AB  - BACKGROUND/AIMS: Fabry disease is an X-linked recessive and progressive disease
      caused by alpha-galactosidase A (alpha-GaL A) deficiency. We sought to assess the
      prevalence of unrecognized Fabry disease in dialysis-dependent patients and the
      efficacy of serum globotriaosylceramide (GL3) screening. METHODS: A total of 480
      patients of 1,230 patients among 17 clinics were enrolled. Serum GL3 levels were
      measured by tandem mass spectrometry. Additionally, we studied the association
      between increased GL3 levels and cardiovascular disease, cerebrovascular disease,
      or left ventricular hypertrophy. RESULTS: Twenty-nine patients had elevated serum
      GL3 levels. The alpha-GaL A activity was determined for the 26 patients with high
      GL3 levels. The mean alpha-GaL A activity was 64.6 nmol/hr/mg (reference range,
      45 to 85), and no patient was identified with decreased alpha-GaL A activity.
      Among the group with high GL3 levels, 15 women had a alpha-GaL A genetics
      analysis. No point mutations were discovered among the women with high GL3
      levels. No correlation was observed between serum GL3 levels and alpha-GaL A
      activity; the Pearson correlation coefficient was 0.01352 (p = 0.9478). No
      significant correlation was observed between increased GL3 levels and the
      frequency of cardiovascular disease or cerebrovascular disease. CONCLUSIONS:
      Fabry disease is very rare disease in patients with end-stage renal disease.
      Serum GL3 measurements as a screening method for Fabry disease showed a high
      false-positive rate. Thus, serum GL3 levels determined by tandem mass
      spectrometry may not be useful as a screening method for Fabry disease in
      patients with end stage renal disease.

PMID- 21179281
TI  - Association of the superoxide dismutase (V16A) and catalase (C262T) genetic
      polymorphisms with the clinical outcome of patients with acute paraquat
      intoxication.
AB  - BACKGROUND/AIMS: Many patients with acute paraquat (PQ) intoxication die even at
      low PQ concentrations, whereas others with similar concentrations recover.
      Therefore, it is possible that individual differences in antioxidant capacity are
      responsible for the variable clinical outcome in patients with acute PQ
      intoxication. METHODS: We investigated whether there was a relationship between
      the genetic polymorphisms of SOD (V16A), catalase (C262T), and GPX1 (C593T) in 62
      patients with acute PQ intoxication and the clinical outcomes of these patients.
      RESULTS: The frequency of the Mn-SOD V/V, V/A, and A/A genotypes were 56.3, 43.5,
      and 0% in survivors and 86.9, 13.1, and 0% in non-survivors (p > 0.05). The GPX1
      C/C, C/T, and T/T genotypes were present in 100, 0, and 0% of all subjects. The
      catalase C/C, C/T, and T/T genotypes were present in 100, 0, and 0% of survivors,
      and in 82.6, 17.4, and 0% of non-survivors. Neither erythrocyte SOD activity nor
      catalase activity were significantly different between survivors and non
      survivors. CONCLUSIONS: No association was found between clinical outcome of
      acute PQ intoxication and the genetic polymorphism of GPX1 (C593T) or the genetic
      polymorphisms or enzyme activity of superoxide dismutase (V16A) or catalase
      (C262T).

PMID- 21179282
TI  - Engagement of toll-like receptor 3 induces vascular endothelial growth factor and
      interleukin-8 in human rheumatoid synovial fibroblasts.
AB  - BACKGROUND/AIMS: Angiogenesis, which is a critical step in the initiation and
      progression of rheumatoid arthritis (RA), involves pro-angiogenic factors,
      including interleukin (IL)-8 and vascular endothelial growth factor (VEGF). We
      investigated the role of Toll-like receptor 3 (TLR3) in the regulation of pro
      angiogenic factors in RA fibroblast-like synoviocytes (FLS). METHODS: FLS were
      isolated from RA synovial tissues and stimulated with the TLR3 ligand, poly
      (I:C). The levels of VEGF and IL-8 in the culture supernatants were measured
      using enzyme-linked immunosorbent assays, and the mRNA levels were assessed by
      semiquantitative reverse transcription-polymerase chain reaction. The expression
      patterns of VEGF and IL-8 in the RA synovium and osteoarthritis (OA) synovium
      were compared using immunohistochemistry. RESULTS: The expression levels of TLR3,
      VEGF, and IL-8 were significantly higher in the RA synovium than in the OA
      synovium. VEGF and IL-8 production were increased in the culture supernatants of
      RA FLS stimulated with poly (I:C), and the genes for these proteins were up
      regulated at the transcriptional level after poly (I:C) treatment. Treatment with
      inhibitors of nuclear factor-kappaB (NF-kappaB), i.e., pyrrolidine
      dithiocarbamate and parthenolide, abrogated the stimulatory effect of poly (I:C)
      on the production of VEGF and IL-8 in RA FLS. CONCLUSIONS: Our results suggest
      that the activation of TLR3 in RA FLS promotes the production of proangiogenic
      factors, in a process that is mediated by the NF-kappaB signaling pathway.
      Therefore, targeting the TLR3 pathway may be a promising approach to preventing
      pathologic angiogenesis in RA.

PMID- 21179283
TI  - A comparison of three different guidelines for osteoporosis treatment in patients
      with rheumatoid arthritis in Korea.
AB  - BACKGROUND/AIMS: Osteoporotic fractures are an important comorbidity with
      rheumatoid arthritis (RA). We determined the overall fracture risk as assessed by
      the World Health Organization (WHO)'s FRAX(r) tool in Korean patients with
      seropositive RA. Additionally, we compared treatment eligibility according to the
      criteria of the Korean Health Insurance Review Agency (HIRA), FRAX, and the
      National Osteoporosis Foundation (NOF). METHODS: Postmenopausal women and men >=
      50 years of age with seropositive RA were recruited from one rheumatism center in
      Korea. The FRAX score was estimated using the Japanese model. Patients were
      classified as eligible for treatment using the HIRA, NOF, and FRAX thresholds for
      intervention. RESULTS: The study of 234 patients included 40 men (17%). The mean
      age was 60 +/- 9 years, and 121 (52%) patients had osteoporosis according to the
      WHO criteria. The overall median 10-year fracture risk was 13% for major
      osteoporotic fractures and 3.5% for hip fractures. HIRA guidelines identified 130
      patients (56%) eligible for treatment, FRAX included 126 patients (54%), and 151
      patients (65%) were included according to NOF guidelines. Older patients with a
      greater number of risk factors were included by FRAX compared to HIRA. The
      overall concordance between HIRA and FRAX, expressed as the kappa index, was
      0.67, but was as low as 0.44 when limited to patients >= 60 years of age.
      CONCLUSIONS: One-half of the patients had osteoporosis requiring treatment. RA
      patients have a high risk of fracture, and the adoption of a risk-scoring system
      should be considered.

PMID- 21179284
TI  - Thalidomide induced nonspecific interstitial pneumonia in patient with relapsed
      multiple myeloma.
AB  - A 63-year-old female diagnosed with relapsed multiple myeloma visited our
      hospital complaining of a persistent cough. Since July 2006, she had been taking
      100 mg thalidomide daily and gradually developed shortness of breath and a
      persistent dry cough. A chest X-ray and computed tomography showed ground glass
      opacities in both lungs. An open lung biopsy of the right middle lobe under
      general anesthesia revealed chronic peribronchial inflammation, mild interstitial
      fibrosis, and intra-alveolar macrophage infiltration, with some hemosiderin
      features, compatible with non-specific interstitial pneumonia (NSIP). After
      discontinuing the thalidomide, the patient's symptoms did not deteriorate,
      although the radiographs did not improve. The patient is alive and well with
      regular outpatient follow-up without progression of the NSIP.

PMID- 21179285
TI  - Anaplastic thyroid carcinoma initially presented with abdominal cutaneous mass
      and hyperthyroidism.
AB  - A 63-year-old female was admitted to our hospital with a tender abdominal wall
      mass about 15 cm in diameter, which she had for 1 month. About 1 week earlier,
      the patient had also perceived a mass in the neck area. Computed tomography
      revealed huge thyroid and periumbilical masses. The thyroid hormone levels were
      consistent with a hyperthyroid state. Pathological examination of the thyroid
      mass was compatible with anaplastic thyroid carcinoma (ATC) and the abdominal
      cutaneous mass was shown to be metastatic ATC. Despite palliative radiotherapy
      and chemotherapy, the patient died of respiratory failure on her 63rd day of
      hospitalization. This case demonstrates that abdominal cutaneous metastasis and
      hyperthyroidism can occur as initial manifestations of ATC. To our knowledge,
      this is the first reported case.

PMID- 21179286
TI  - Postoperative high-dose intravenous iron sucrose with low dose erythropoietin
      therapy after total hip replacement.
AB  - Erythropoietin combined with parenteral iron sucrose therapy is an alternative to
      blood transfusion in anemic patients. It was shown to be effective in surgical
      patients in several previous studies when used in conjunction with other methods.
      However, there are no guidelines about safety limits in dosage amounts or
      intervals. In this study, we report a case of significant postoperative
      hemorrhage managed with high dose parenteral iron sucrose, low dose
      erythropoietin, vitamin B(12), vitamin C, and folic acid. An 80-year-old female
      patient presented for severe anemia after a total hip arthroplasty and refused an
      allogenic blood transfusion as treatment. The preoperative hemoglobin of 12.2
      g/dL decreased to 5.3 g/dL postoperatively. She received the aforementioned
      combination of iron sucrose, erythropoietin, and vitamins. A total of 1,500 mg of
      intravenous iron sucrose was given postoperatively for 6 consecutive days.
      Erythropoietin was also administered at 2,000 IU every other day for a total of
      12,000 IU. The patient was discharged in good condition on the twelfth
      postoperative day with a hemoglobin of 8.5 g/dL. Her hemoglobin was at 11.2 g/dL
      on the twentieth postoperative day.

PMID- 21179287
TI  - A case of spontaneous hemoperitoneum presenting as the initial manifestation of
      systemic lupus erythematosus.
AB  - Thrombocytopenia is included in the classification criteria for systemic lupus
      erythematosus (SLE). However, severe thrombocytopenia causing spontaneous
      bleeding is rare. Here, we describe a 22-year-old woman who presented with
      spontaneous hemoperitoneum as the first manifestation of SLE. Laboratory findings
      compatible with SLE included positive antinuclear antibody and a false-positive
      venereal disease research laboratory. Symptoms suggesting the disease were not
      prominent early after admission, but headache and seizures that developed on the
      3rd day of admission led to the diagnosis of SLE. The brain magnetic resonance
      imaging and angiography findings were compatible with the neuropsychiatric
      manifestations of SLE. High-dose steroid and monthly intravenous cyclophosphamide
      pulse therapy were effective at improving the headache and seizure, as well as
      the hemoperitoneum.

PMID- 21179288
TI  - Pain on injection with propofol.

PMID- 21179289
TI  - Therapeutic hypothermia.
AB  - Pioneer works on therapeutic hypothermia (TH) half a century ago already showed
      promising results but clinical application was limited by a lack of understanding
      of the underlying pathophysiology, lack of reliable method for temperature
      control and lack of intensive care facilities to deal with possible
      complications. More recently, 2 studies in 2002 supported the application of
      moderate TH (32.0-34.0C) in post-cardiac arrest patients. Although the studies
      included only patients suffering from out-of-hospital VF, many ICUs world-wide
      are applying the therapy to all post-cardiac arrest patients irrespective of site
      or presenting rhythm. While primary coagulopathy and cardiogenic shock are
      usually stated as relative contraindications, evidences are accumulating to
      support the application of TH in patients with cardiogenic shock. TH can be
      divided into 4 phases: Induction, maintenance, de-cooling and normothermia.
      Induction is usually achieved by infusion of cold isotonic fluid. The precautions
      included avoidance of over-cooling, hypokalaemia, hyperglycaemia, and shivering.
      TH can be maintained by many different methods, varying in their level of
      invasiveness, cost and effectiveness. Issues including changes in
      pharmacokinetics and haemodynamics, and susceptibility to infection need to the
      addressed. The optimal duration of maintenance is unknown but the usual practice
      is 12-24 hours. De-cooling and rewarming is especially challenging because
      complications can be serious if temperature rise by more than 1C every 3-5 hours.
      Life-theatening hyperkalaemia can occur especially if patient suffers from renal
      insufficiency. Fever is a frequent complication either due to infection or post
      cardiac arrest syndrome but patient must be kept normothermic for 72 hours.

PMID- 21179290
TI  - Efficacy of the combination of cold propofol and pretreatment with remifentail on
      propofol injection pain.
AB  - BACKGROUND: Pain upon the injection of propofol is a common adverse effect. This
      study was conducted to evaluate the analgesic effect of remifentanil and cold
      propofol during propofol injection for the induction of anesthesia and to
      determine if a combination of cold propofol and remifentanil produced additional
      analgesic efficacy. METHODS: A total of 160 patients aged 20-65 years old were
      randomly allocated into one of four groups (n = 40, in each). Control and
      remifentanil group patients received 2 mg/kg propofol that had been stored at
      room temperature (20-23C), while the cold and combination group received cold
      (4C) propofol. The patients received remifentanil 0.5 ug/kg IV in the
      remifentanil and combination groups or saline in the control and cold groups.
      Ninety seconds after administration the patients were administered propofol over
      a 30 second period. The pain intensity and incidence were then evaluated using a
      4-point verbal rating scale. RESULTS: The incidence of pain was significantly
      reduced in groups that received remifentanil in the cold and combination groups
      when compared with the control group (27.5%, 30%, and 2.5% vs. 70%,
      respectively). Moreover, the severity of pain was significantly lower in groups
      that received remifentanil in the cold and combination groups when compared with
      the control group. The incidence and severity of pain from the propofol injection
      in the combination group was significantly lower than that in the remifentanil
      and cold groups. CONCLUSIONS: The combination of cold propofol and pretreatment
      with remifentanil more effectively reduced the incidence of pain upon the
      injection of propofol than either treatment alone.

PMID- 21179291
TI  - Prevention of pain during injection of microemulsion propofol: application of
      lidocaine mixture and the optimal dose of lidocaine.
AB  - BACKGROUND: Similar to lipid emulsion propofol, microemulsion propofol also
      causes a high incidence of pain during intravenous injection. Various methods
      have been used to minimize the incidence and severity of pain on injection of
      lipid emulsion propofol. In this study, we investigated the effect of a lidocaine
      mixture on pain induced by microemulsion propofol injection, and sought to
      determine the optimal dose of lidocaine that could reduce pain on injecting a
      propofol-lidocaine mixture. METHODS: One hundred sixty (n = 160) patients of
      American Society of Anesthesiologists physical status class I or II were randomly
      allocated to four groups: Group A, control; Group B, 20 mg lidocaine; Group C, 30
      mg lidocaine; Group D, 40 mg lidocaine. In each patient, pain on microemulsion
      propofol solution injection was graded as none, mild, moderate, or severe.
      RESULTS: The incidence of pain in groups A, B, C, and D was 97.5%, 80%, 65%, and
      50%, respectively. Increasing the lidocaine dose significantly reduced pain (P <
      0.05). One patient in Group D (2.5%) had moderate to severe pain, which was
      significantly lower than groups B (42.5%) and C (32.5%) (P < 0.05). CONCLUSIONS:
      The lidocaine and propofol mixture is effective in alleviating pain associated
      with microemulsion propofol injection. Within this dose range and in this
      patients population, increasing lidocaine dosage significantly reduced pain
      during injection of microemulsion propofol.

PMID- 21179292
TI  - Comparison of the laryngeal view during intubation using Airtraq and Macintosh
      laryngoscopes in patients with cervical spine immobilization and mouth opening
      limitation.
AB  - BACKGROUND: For patients suspicious of cervical spine injury, a Philadelphia
      cervical collar is usually applied. Application of Philadelphia cervical collar
      may cause difficult airway. The aim of this study was to evaluate the laryngeal
      view and the success rate at first intubation attempt of the Airtraq and
      conventional laryngoscopy in patients with simulated cervical spine injury after
      application of a Philadelphia cervical collar. METHODS: Anesthesia was induced
      with propofol, remifentanil, and rocuronium. After a Philadelphia cervical collar
      applied, patients were randomly assigned to tracheal intubation with an Airtraq
      (Group A, n = 25) or with conventional laryngoscopy (Group L, n = 25).
      Measurements included intubation time, success rate of first intubation attempt,
      number of intubation attempts, and percentage of glottic opening (POGO) score.
      Mean blood pressure and heart rate were also recorded at baseline, just before
      and after intubation. RESULTS: The success rate of the first attempt in Group A
      (96%) was significantly greater than with the Group L (40%). POGO score was
      significantly greater in Group A (84 +/- 20%) than in Group L (6 +/- 11%). The
      duration of successful intubation at first tracheal intubation attempt and
      hemodynamic changes were not significantly different between the two groups.
      CONCLUSIONS: The Airtraq offers a better laryngeal view and higher success rate
      at first intubation attempt in patients who are applied with a Philadelphia
      cervical collar due to suspicion of cervical spine injury.

PMID- 21179293
TI  - Comparison of the effectiveness of lidocaine and salbutamol on coughing provoked
      by intravenous remifentanil during anesthesia induction.
AB  - BACKGROUND: Coughing is a side effect of opioids that is rarely studied. Here, we
      evaluated the incidence of remifentanil induced coughing during anesthesia
      induction in an attempt to identify its risk factors and to examine the
      preventive effects of lidocaine and salbutamol. METHODS: A total of 237 patients
      scheduled to undergo general anesthesia were allocated randomly into three
      groups. Group C received no medication, while Group L received 2% lidocaine at
      0.5 mg/kg intravenously 1 minute prior to remifentanil infusion and Group S
      inhaled one metered aerosol puff of salbutamol 15 minutes prior to entering the
      operating room. Remifentanil was infused at 5 ng/ml by target controlled infusion
      and coughing was measured for five minutes and graded as none, mild, moderate, or
      severe based on the number of coughs. RESULTS: The incidences of coughing were
      30.4%, 25.3%, and 35.4% in Groups C, L, and S, respectively. The incidences,
      onset times, and severity of coughing did not differ significantly among groups.
      In addition, multivariate analysis showed that non-smoking and a lower body
      weight were risk factors of remifentanil-induced coughing (odds ratio, 8.13; P =
      0.024, 1.11, and 0.004, respectively). CONCLUSIONS: The incidence of remifentanil
      induced coughing was 30%. A total of 0.5 mg/kg lidocaine and 1 metered aerosol
      puff of salbutamol did not prevent coughing. Non-smoking and low body weight were
      found to be risk factors of remifentanil-induced coughing.

PMID- 21179294
TI  - The effect on respiratory mechanics when using a Jackson surgical table in the
      prone position during spinal surgery.
AB  - BACKGROUND: Respiratory dynamics may be monitored and evaluated indirectly by
      measuring the peak inspiratory pressure and plateau pressure. In this study, the
      respiratory dynamics of patients undergoing spinal surgery using a Jackson
      surgical table were observed with a device after converting their position from
      supine to prone. The effects of the dynamic compliance and airway resistance were
      observed from the changes in peak inspiratory pressure and plateau. METHODS:
      Twenty five patients were selected as subjects scheduled to undergo lumbar spine
      surgery. After intubation, the patients were ventilated mechanically with a tidal
      volume of 10 ml/kg and a respiration rate of 10/min. Anesthesia was maintained
      with sevoflurane 1.5%, nitrous oxide 2 L/min and oxygen 2 L/min. The peak
      inspiratory pressure, plateau pressure, resistance, compliance, arterial oxygen
      tension, carbon dioxide tension, heart rate and arterial blood pressure were
      measured at 10 minutes after the induction of anesthesia. These parameters were
      measured again 10 minutes after placing the patient in the prone position.
      RESULTS: The prone position did not significantly affect the arterial oxygen
      tension, carbon dioxide tension, blood pressure and heart rate, but significantly
      increased the peak inspiratory pressure and resistance and decreased the dynamic
      compliance. CONCLUSIONS: The peak inspiratory pressure was increased using a
      Jackson surgical table to minimize the abdominal pressure when converting from
      the supine to prone position. This might be due to a decrease in lung and chest
      compliance as well as an increase in airway resistance.

PMID- 21179295
TI  - The effect of pneumoperitoneum and Trendelenburg position on respiratory
      mechanics during pelviscopic surgery.
AB  - BACKGROUND: Conventional pelviscopic surgery requires pneumoperitoneum with CO(2)
      gas insufflation and lithotomy-Trendelenburg position. Pneumoperitoneum and
      Trendelenburg position may influence intraoperative respiratory mechanics in
      anesthetic management. This study was conducted to investigate the influence of
      pneumoperitoneum and Trendelenburg position on respiratory compliance and
      ventilation pressure. METHODS: Twenty-five patients scheduled for elective
      gynecologic laparoscopy were evaluated. The patients had no preexisting lung or
      heart disease or pathologic lung function. Conventional general anesthesia with
      thiopental sodium, lidocaine, rocuronium, and sevoflurane was administered. The
      peak inspiratory pressure, plateau pressure, and end-tidal CO(2) were measured
      before and after creation of pneumoperitoneum with an intraabdominal pressure of
      12 mmHg, then after 10 minutes and 30 minutes in the 20 degrees  Trendelenburg
      position, and after deflation of pneumoperitoneum. The dynamic lung compliance
      was then calculated. RESULTS: Following creation of pneumoperitoneum, there was a
      significant increase in peak inspiratory pressure (6 cmH(2)O), plateau pressure
      (7 cmH(2)O), and end-tidal CO(2) (5 mmHg), while dynamic lung compliance
      decreased by 12 ml/cmH(2)O. Overall, the Trendelenburg position induced no
      significant hemodynamic or pulmonary changes. CONCLUSIONS: The effects of
      pneumoperitoneum significantly reduced dynamic lung compliance and increased peak
      inspiratory and plateau pressures. The Tredelenburg position did not change these
      parameters.

PMID- 21179296
TI  - Prophylactic antiemetic effects in gynecologic patients receiving fentanyl IV
      patient controlled analgesia: comparison of combined treatment with ondansetron
      and dexamethasone with metoclopramide and dexamethasone.
AB  - BACKGROUND: This study was conducted to compare the efficacy of a combination of
      ondansetron and dexamethasone with that of metoclopramide and dexamethasone for
      prevention of postoperative nausea and vomiting (PONV) in gynecologic patients
      receiving fentanyl IV-patient controlled analgesia. METHODS: One hundred patients
      were divided into two groups at random. In Group O, 5 mg of dexamethsone was
      administered after tracheal intubation, while 4 mg of ondansetron was
      administered at the end of surgery. In Group M, 5 mg of dexamethsone was
      administered after tracheal intubation and 20 mg metoclopromide was administered
      at the end of surgery. During the experiment, the PONV was evaluated at regular
      intervals. In addition, the incidence of nausea, and vomiting and the numerical
      rating scale (NRS) of nausea was measured (range, 0-10). RESULTS: The overall
      incidence of PONV in Group O was 22/50 (44%) while that in Group M was 19/50
      (38%). There were no significant differences in the incidence of nausea, moderate
      to severe nausea (NRS of nausea, 4-10), or vomiting between groups. CONCLUSIONS:
      Treatment with a combination of 20 mg metoclopramide and 5 mg dexamethasone is an
      effective, safe, and inexpensive way to prevent PONV when compared to treatment
      with 4 mg ondansetron and 5 mg dexamethasone.

PMID- 21179297
TI  - Anesthetic experience of methemoglobinemia detected during general anesthesia for
      gastrectomy of advanced gastric cancer -A case report-.
AB  - Methemoglobinemia is an uncommon but potentially fatal disorder. Most cases have
      no adverse clinical consequence and require no treatment, but methemoglobinemia
      is often overlooked as a cause of low oxygen saturation, and often mistaken for
      the more common causes of hypoxia by anesthesiologists despite simple bedside
      tests that indicate the presence of this treatable abnormality. We present a 68
      year-old female patient who underwent gastrectomy for advanced gastric cancer
      with bleeding. In the preoperative period, the patient showed cyanosis and oxygen
      saturation was 85% by pulse oximeter, but oxygen saturation by arterial blood gas
      analysis was 100%. After tracheal intubation, the methemoglobin level was 18.3%.
      Ascorbic acid and methylene blue were administered. During preanesthetic
      evaluation, the patient had not informed the anesthesiologist that she had been
      taking dapsone.

PMID- 21179298
TI  - Intercostal misplacement of a thoracic epidural catheter -A case report-.
AB  - Epidural block is useful for chronic pain and thoracic surgery. However, there
      are several complications, which include vessels or dural puncture, pleural
      puncture, misplacement of epidural catheter and trauma to the spinal cord. We
      report a case of intercostal misplacement of an epidural catheter in a 66-year
      old patient who scheduled for left thoracotomy.

PMID- 21179299
TI  - Two-stage liver transplantation in a surgically complicated liver failure patient
      after hepatic tumor resection -A case report-.
AB  - Two-stage liver transplantation, involving a total hepatectomy with a temporary
      portocaval shunt followed by liver transplantation, requires intensive
      perioperative care, especially during the prolonged anhepatic period. The
      pathophysiology and management of this prolonged anhepatic state is not fully
      elucidated and the proper management during this period is a great challenge to
      clinicians in the intensive care unit and anesthesiologists. We report a case and
      management of a total hepatectomy with a temporary portocaval shunt followed by
      living-donor liver transplantation in a patient with a surgically complicated
      liver failure after a hepatic tumor resection.

PMID- 21179300
TI  - Combined epidural anesthesia and ultrasound guided peripheral nerve block for
      wound revision in a patient with peripartum cardiomyopathy -A case report-.
AB  - Peripartum cardiomyopathy (PPCM) is a rare complication that occurs between the
      late stage of pregnancy and six months after delivery. PPCM presents as symptoms
      of left ventricular dysfunction and it can be fatal unless treated promptly.
      Furthermore, anesthesia and surgery in such patients is a large challenge to
      anesthesiologists. First and foremost, the maintenance of stable hemodynamics is
      a major concern. We report a case of combined lumbar epidural anesthesia and both
      ilioinguinal and iliohypogastric nerve block under ultrasound guided for a wound
      revision in a 37-year-old woman diagnosed with PPCM after an emergency cesarean
      section.

PMID- 21179301
TI  - Anesthetic management of the emergency laparotomy for a patient with multiple
      sclerosis -A case report-.
AB  - A 33-year-old male patient with multiple sclerosis (MS) received an emergency
      laparotomy because of perforated appendicitis. He had been suffering from MS for
      2 years and the symptoms of MS were paraplegia and urinary incontinence.
      Anesthesia was induced with propofol and remifentanil and maintained with nitrous
      oxide, sevoflurane and remifentanil. Rocuronium was used for tracheal intubation.
      Train of four ratio and bispectral index scale were also monitored for adequate
      muscle relaxation and anesthetic depth. The patient emerged from general
      anesthesia smoothly and was extubated without any complication. Postoperative
      exacerbation of MS symptoms did not appear. However, he was rehospitalized
      because deep vein thrombosis (DVT) occurred after discharge and he received
      heparinization immediately. Eventually, he was discharged after a full recovery
      from DVT. We report a safe anesthetic management of the patient with MS, with the
      use of sevoflurane and with no the aggravation of MS during postoperative period.

PMID- 21179302
TI  - Role of dendritic cells in cardiovascular diseases.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells that bridge innate and
      adaptive immune responses. Recent work has elucidated the DC life cycle,
      including several important stages such as maturation, migration and homeostasis,
      as well as DC classification and subsets/locations, which provided etiological
      insights on the role of DCs in disease processes. DCs have a close relationship
      to endothelial cells and they interact with each other to maintain immunity. DCs
      are deposited in the atherosclerotic plaque and contribute to the pathogenesis of
      atherosclerosis. In addition, the necrotic cardiac cells induced by ischemia
      activate DCs by Toll-like receptors, which initiate innate and adaptive immune
      responses to renal, hepatic and cardiac ischemia reperfusion injury (IRI).
      Furthermore, DCs are involved in the acute/chronic rejection of solid organ
      transplantation and mediate transplant tolerance as well. Advancing our knowledge
      of the biology of DCs will aid development of new approaches to treat many
      cardiovascular diseases, including atherosclerosis, cardiac IRI and
      transplantation.

PMID- 21179303
TI  - Linking inflammation and thrombosis: Role of C-reactive protein.
AB  - C-reactive protein (CRP) is a biomarker of inflammation. Increased plasma levels
      of CRP are associated with an increased risk of myocardial infarction. However,
      the correlation between plasma CRP concentration and atherosclerotic plaque
      burden is poor. Based on these observations, it has been hypothesized that CRP
      increases the risk of myocardial infarction by promoting thrombosis. This article
      reviews available data that link enhanced CRP expression to increased risk of
      thrombosis, with a focus on the effects of CRP on hemostasis, platelet function,
      and fibrinolysis. Overall, the available data support the hypothesis that CRP is
      an important mechanistic link between inflammation and thrombosis.

PMID- 21179304
TI  - Emerging role of adipokines as mediators in atherosclerosis.
AB  - Atherosclerotic cardiovascular disease is a major health problem around the
      world. Obesity is a primary risk factor for atherosclerosis and is associated
      with increased morbidity and mortality of cardiovascular diseases. However, the
      precise molecular pathways underlying this close association remain poorly
      understood. Adipokines are cytokines, chemokines and hormones secreted by adipose
      tissue that couple the regulation of lipid accumulation, inflammation, and
      atherogenesis, and therefore serve to link obesity with cardiovascular disorders.
      Obesity-related disorders including metabolic syndrome, diabetes,
      atherosclerosis, hypertension, and coronary artery disease are associated with
      dysregulated adipokine(s) expression. Recent studies demonstrate the
      proinflammatory effects as well as atherogenic properties of adipokines.
      Adipokines also participate in the regulation of endothelial function, which is
      an early event in atherosclerosis. By contrast, adiponectin, an adipocyte-derived
      hormone, exerts anti-inflammatory, anti-atherogenic and vascular protective
      effects. Furthermore, there is an interactive association among adipokines, by
      which adipokines reciprocally regulate each other's expression. Understanding
      this interplay may reveal plausible mechanisms for treating atherosclerosis and
      coronary heart disease by modulating adipokine(s) expression. In this review, we
      discuss insights into the role and the therapeutic potential of adipokines as
      mediators of atherosclerosis.

PMID- 21179305
TI  - Coronary microvascular dysfunction in diabetes mellitus: A review.
AB  - The exploration of coronary microcirculatory dysfunction in diabetes has
      accelerated in recent years. Cardiac function is compromised in diabetes.
      Diabetic patients manifest accelerated atherosclerosis in coronary arteries.
      These data are confirmed in diabetic animal models, where lesions of small
      coronary arteries have been described. These concepts are epitomized in the
      classic microvascular complications of diabetes, i.e. blindness, kidney failure
      and distal dry gangrene. Most importantly, accumulating data indicate that
      insights gained from the link between inflammation and diabetes can yield
      predictive and prognostic information of considerable clinical utility. This
      review summarizes the evidence for the predisposing factors and the mechanisms
      involved in diabetes, and assesses the current state of knowledge regarding the
      triggers for inflammation in this disease. We evaluate the roles of
      hyperglycemia, oxidative stress, polyol pathway, protein kinase C, advanced
      glycation end products, insulin resistance, peroxisome proliferator-activated
      receptor-gamma, inflammation, and diabetic cardiomyopathy as a "stem cell
      disease". Furthermore, we discuss the mechanisms responsible for impaired
      coronary arteriole function. Finally, we consider how new insights in diabetes
      may provide innovative therapeutic strategies.

PMID- 21179306
TI  - Mediastinitis in pediatric cardiac surgery: Prevention, diagnosis and treatment.
AB  - In spite of advances in the management of mediastinitis following sternotomy,
      mediastinitis is still associated with significant morbidity. The prognosis is
      much better in pediatric surgery compared to adult surgery, but the prolonged
      hospital stays with intravenous therapy and frequent required dressing changes
      that occur with several therapeutic approaches are poorly tolerated. Prevention
      includes nasal decontamination, skin preparation, antibioprophylaxis and air
      filtration in the operating theater. The expertise of the surgical team is an
      additional factor that is difficult to assess precisely. Diagnosis is often very
      simple, being made on the basis of a septic state with wound modification, while
      retrosternal puncture and CT scan are rarely useful. Treatment of mediastinitis
      following sternotomy is always a combination of surgical debridement and
      antibiotic therapy. Continued use of numerous surgical techniques demonstrates
      that there is no consensus and the best treatment has yet to be determined.
      However, we suggest that a primary sternal closure is the best surgical option
      for pediatric patients. We propose a simple technique with high-vacuum Redon's
      catheter drainage that allows early mobilization and short term antibiotherapy,
      which thus decreases physiological and psychological trauma for patients and
      families. We have demonstrated the efficiency of this technique, which is also
      cost-effective by decreasing intensive care and hospital stay durations, in a
      large group of patients.

PMID- 21179307
TI  - Walking with Gianluca Di Bella during the development of clinical cardiac
      imaging.
AB  - Cardiac magnetic resonance imaging (MRI) for the diagnosis and management of many
      cardiac diseases has been established in clinical practice. It provides anatomic
      and functional information and is the most precise technique for quantification
      of ventricular volume, function and mass. Among cardiac MRI sequences used in
      clinical practice, delayed contrast enhancement is an accurate and reliable
      method used in the diagnosis of ischemic and nonischemic cardiomyopathies. In
      addition, new technology applied in echocardiographic imaging has permitted
      quantification of myocardial deformations with 2-dimensional strain imaging
      (longitudinal, circumferential and radial strain). Cardiac MRI and
      echocardiography therefore both play a crucial role in the diagnosis and
      management of cardiovascular disease. Dr. Di Bella and colleagues have defined
      the roles of cardiac MRI and echocardiography in many clinical and experimental
      settings.

PMID- 21179309
TI  - Technological innovations in digital data management and changing roles of
      imaging specialists in Japan.
AB  - Technical innovations in digital data management pose a threat to radiologists in
      that can we remain in the process of clinical decision making or be assigned to a
      secondary role in future clinical practice. The value added to the imaging
      studies by diagnostic radiologists, or imaging specialists, has never been
      questioned more seriously.

PMID- 21179308
TI  - Radiofrequency ablation of hepatocellular carcinoma: Current status.
AB  - Ablation therapy is one of the best curative treatment options for malignant
      liver tumors, and can be an alternative to resection. Radiofrequency ablation
      (RFA) of primary and secondary liver cancers can be performed safely using
      percutaneous, laparoscopic, or open surgical techniques, and RFA has markedly
      changed the treatment strategy for small hepatocellular carcinoma (HCC).
      Percutaneous RFA can achieve the same overall and disease-free survival as
      surgical resection for patients with small HCC. The use of a laparoscopic or open
      approach allows repeated placements of RFA electrodes at multiple sites to ablate
      larger tumors. RFA combined with transcatheter arterial chemoembolization will
      make the treatment of larger tumors a clinically viable treatment alternative.
      However, an accurate evaluation of treatment response is very important to secure
      successful RFA therapy. Since a sufficient safety margin (at least 0.5 cm) can
      prevent local tumor recurrences, an accurate evaluation of treatment response is
      very important to secure successful RFA therapy. To minimize complications of
      RFA, clinicians should be familiar with the imaging features of each type of
      complication. Appropriate management of complications is essential for successful
      RFA treatment.

PMID- 21179310
TI  - Pathophysiology of nephrogenic systemic fibrosis: A review of experimental data.
AB  - Since the association between nephrogenic systemic fibrosis (NSF) and gadolinium
      contrast agents (Gd-CAs) was suggested in 2006, several experimental studies have
      been published to elucidate the role of these agents in the pathogenesis of NSF.
      Low stability Gd-CAs have a stimulant effect on human skin and fibroblasts in
      culture and modulate the production of collagen by these cells. Low stability
      agents have also induced NSF-like skin changes in a rat model with normal renal
      function after multiple repeat administrations. The role of the 5/6 subtotal
      nephrectomy rat model in investigating NSF remains under evaluation.

PMID- 21179311
TI  - Peripheral dose measurement in high-energy photon radiotherapy with the
      implementation of MOSFET.
AB  - AIM: To study the peripheral dose (PD) from high-energy photon beams in
      radiotherapy using the metal oxide semiconductor field effect transistor (MOSFET)
      dose verification system. METHODS: The radiation dose absorbed by the MOSFET
      detector was calculated taking into account the manufacturer's Correction Factor,
      the Calibration Factor and the threshold voltage shift. PD measurements were
      carried out for three different field sizes (5 cm * 5 cm, 10 cm * 10 cm and 15 cm
      * 15 cm) and for various depths with the source to surface distance set at 100
      cm. Dose measurements were realized on the central axis and then at distances (1
      to 18 cm) parallel to the edge of the field, and were expressed as the percentage
      PD (% PD) with respect to the maximum dose (d(max)). The accuracy of the results
      was evaluated with respect to a calibrated 0.3 cm(3) ionization chamber. The
      reproducibility was expressed in terms of standard deviation (s) and coefficient
      of variation. RESULTS: % PD is higher near the phantom surface and drops to a
      minimum at the depth of d(max), and then tends to become constant with depth.
      Internal scatter radiation is the predominant source of PD and the depth
      dependence is determined by the attenuation of the primary photons. Closer to the
      field edge, where internal scatter from the phantom dominates, the % PD increases
      with depth because the ratio of the scatter to primary increases with depth. A
      few centimeters away from the field, where collimator scatter and leakage
      dominate, the % PD decreases with depth, due to attenuation by the water. The %
      PD decreases almost exponentially with the increase of distance from the field
      edge. The decrease of the % PD is more than 60% and can reach up to 90% as the
      measurement point departs from the edge of the field. For a given distance, the %
      PD is significantly higher for larger field sizes, due to the increase of the
      scattering volume. Finally, the measured PD obtained with MOSFET is higher than
      that obtained with an ionization chamber with percentage differences being from
      0.6% to 34.0%. However, when normalized to the central d(max) this difference is
      less than 1%. The MOSFET system, in the early stage of its life, has a dose
      measurement reproducibility of within 1.8%, 2.7%, 8.9% and 13.6% for 22.8, 11.3,
      3.5 and 1.3 cGy dose assessments, respectively. In the late stage of MOSFET life
      the corresponding values change to 1.5%, 4.8%, 11.1% and 29.9% for 21.8, 2.9, 1.6
      and 1.0 cGy, respectively. CONCLUSION: Comparative results acquired with the
      MOSFET and with an ionization chamber show fair agreement, supporting the
      suitability of this measurement for clinical in vivo dosimetry.

PMID- 21179312
TI  - Multislice CT virtual intravascular endoscopy of aortic dissection: A pictorial
      essay.
AB  - AIM: To present our experience of using 3D virtual intravascular endoscopy (VIE)
      to characterize and evaluate the intraluminal appearances of aortic dissection.
      METHODS: Ten patients with known aortic dissection underwent dual-source computed
      tomography angiography and were included in the study. In addition to 2D axial
      and multiplanar reformatted images as well as 3D reconstructions, VIE images were
      created in each patient to demonstrate intraluminal views of the aorta and its
      branches, origin of artery branches and artery branch involvement by aortic
      dissection. RESULTS: Stanford A dissection was found in 8 patients and B
      dissection in the remaining 2 patients. VIE images were successfully generated in
      all of the patients with excellent visualization of the normal anatomical
      structures, intimal flap and intimal entrance tear, communication between true
      and false lumens, as well as assessment of the extent of aortic dissection.
      CONCLUSION: Our preliminary experience suggests that VIE could be used as a
      complementary tool to assist radiologists accurately evaluate aortic dissection
      so that better patient management can be achieved.

PMID- 21179313
TI  - Perfusion characterization of liver metastases from endocrine tumors: Computed
      tomography perfusion.
AB  - AIM: To assess prospectively parameters of computed tomography perfusion (CT p)
      for evaluation of vascularity of liver metastases from neuroendocrine tumors.
      METHODS: This study was approved by the hospital's institutional review board.
      All 18 patients provided informed consent. There were 30 liver metastases from
      neuroendocrine tumors. Patients were divided into three groups depending on the
      appearance of the liver metastases at the arterial phase of morphological CT
      (hyperdense, hypodense and necrotic). Sequential acquisition of the liver was
      performed before and for 2 min after intravenous injection of 0.5 mg/kg contrast
      medium, at 4 mL/s. Data were analyzed using deconvolution analysis to calculate
      blood flow (BF), blood volume (BV), mean transit time (MTT), hepatic arterial
      perfusion index (HAPI) and a bi-compartmental analysis was performed to obtain
      vascular permeability-surface area product (PS). Post-treatment analysis was
      performed by a radiologist and regions of interest were plotted on the
      metastases, normal liver, aorta and portal vein. RESULTS: At the arterial phase
      of the morphological CT scan, the aspects of liver metastases were hyperdense (n
      = 21), hypodense (n = 7), and necrotic (n = 2). In cases of necrotic metastases,
      none of the CT p parameters were changed. Compared to normal liver, a significant
      difference in all CT p parameters was found in cases of hyperdense metastases,
      and only for HAPI and MTT in cases of hypodense metastases. No significant
      difference was found for MTT and HAPI between hypo- and hyperdense metastases. A
      significant decrease of PS, BV and BF was demonstrated in cases of patients with
      hypodense lesions PS (23 +/- 11.6 mL/100 g per minute) compared to patients with
      hyperdense lesions; PS (13.5 +/- 10.4 mL/100 g per minute), BF (93.7 +/- 75.4 vs
      196.0 +/- 115.6 mL/100 g per minute) and BV (9.7 +/- 5.9 vs 24.5 +/- 10.9 mL/100
      g). CONCLUSION: CT p provides additional information compared to the
      morphological appearance of liver metastases.

PMID- 21179314
TI  - Synthesis and antimicrobial activity of long-chain 3,4-Epoxy-2-alkanones.
AB  - 3,4-Epoxy-2-dodecanone, a major component in the preorbital gland of the African
      grey duiker (Sylvicapra grimmia), showed antimicrobial activity in preliminary
      tests. The C(11) to C(17) homologues of this compound were prepared and their
      activity against several pathogenic dermal bacteria and fungi was tested. 3,4
      Epoxy-2-dodecanone and 3,4-epoxy-2-tridecanone inhibited the growth of
      Trichophyton mentagrophytes at 25 Ig/mL. Moderate inhibition of the growth of the
      bacteria Propionibacterium acnes and the lipophilic yeast, Pityrosporum ovale,
      was seen for several of the homologues.

PMID- 21179315
TI  - New 4-thiazolidinones of nicotinic acid with 2-Amino-6-methylbenzothiazole and
      their biological activity.
AB  - The title compounds 6aaj, 2-[(6-methyl-1,3-benzothiazol-2-yl)amino]-N-[2
      (substituted phenyl/furan-2-yl)-4-oxo-1,3-thiazolidin-3-yl]nicotinamides, were
      prepared from 2-chloropyridine-3-carboxylic acid (1) and 2-amino-6-methyl
      benzothiazole (2) by known methods. All the compounds have been established by
      IR, (1)H NMR, (13)C NMR and elemental analyses. The in vitro antimicrobial
      screening of the compounds were carried out against two Gram positive (S. aureus,
      S. pyogenes), two Gram negative (E. coli, P. aeruginosa) bacteria and three
      fungal species (C. albicans, A. niger, A. clavatus) using the broth microdilution
      method. Some of the compounds are comparable with standard drugs.

PMID- 21179316
TI  - Synthesis, photochemical and photoinduced antibacterial activity studies of meso
      Tetra(pyren-1-yl)porphyrin and its Ni, Cu and Zn complexes.
AB  - The synthesis of the meso-tetra(pyren-1-yl)porphyrin (1) was successfully
      accomplished by means of the pyrrole condensation with pyrene-1-carb-aldehyde in
      acidic media. Its metallization was carried out in an almost quantitative yield
      to obtain the corresponding complexes of Ni(II) (2), Cu(II) (3) and Zn (4). Their
      photophysical properties such as fluorescence quantum yield and energy transfer
      to oxygen for an efficient generation of singlet oxygen were determined. Their
      photophysical and photochemical properties were compared with those of other
      similar porphyrin derivatives such as tetraphenylporphyrin and
      tetranaphthylporphyrin. Photochemical studies on their effectiveness as
      photosensitizer were carried out by means of the photoinduced oxidation of
      aromatic alcohols like I-naphthol to naphthoquinone. The antibacterial
      photoactivity assay for compounds 1a4 was testeted against Escherichia coli (ATCC
      8739) and its proliferation and viability were measured by chemiluminescence. An
      efficient inactivation of E. coli was observed. This was more efficient for
      compounds 2 and 3, following the direct relationship to high generation of
      singlet oxygen by these compounds.

PMID- 21179318
TI  - Simultaneous quantitative determination of metoprolol, atorvastatin and ramipril
      in capsules by a validated stability-indicating RP-UPLC method.
AB  - A simple ultra performance liquid chromatographic (UPLC) method has been
      developed for the simultaneous estimation of Metoprolol (MT), Atorvastatin (AT)
      and Ramipril (RM) from capsule dosage form. The method was developed using
      ZorbaxA XDB-C18 (4.6 mm A 50 mm, 1.8 Im) column with a mobile phase consisting of
      0.06% ortho phosphoric acid in Milli QA water having an ion pair reagent, 0.0045
      M Sodium lauryl sulphate as buffer, at ratio of buffer: Acetonitrile (50:50 v/v),
      at 55AC column temperature with a flow rate of 1.0 ml/min. Detection was carried
      out with ultra-violet detection at 210 nm for RM, MT and AT respectively. The
      retention times were about 1.3, 2.1 and 2.6 min for MT, AT and RM respectively,
      the method was validated for linearity, accuracy, precision, specificity,
      robustness and ruggedness. The % mean recoveries are 101.9, 102.1 and 101.4 for
      MT, AT and RM respectively. The method was found to be rugged and robust and can
      be successfully used to determine the three drugs and its combinations.

PMID- 21179317
TI  - Models for antitubercular activity of 5a-O-[(N-Acyl)sulfamoyl]adenosines.
AB  - The relationship between topological indices and antitubercular activity of 5a-O
      [(N-Acyl)sulfamoyl]adenosines has been investigated. A data set consisting of 31
      analogues of 5a-O-[(N-Acyl)sulfamoyl]adenosines was selected for the present
      study. The values of numerous topostructural and topochemical indices for each of
      31 differently substituted analogues of the data set were computed using an in
      house computer program. Resulting data was analyzed and suitable models were
      developed through decision tree, random forest and moving average analysis (MAA).
      The goodness of the models was assessed by calculating overall accuracy of
      prediction, sensitivity, specificity and Mathews correlation coefficient.
      Pendentic eccentricity index a a novel highly discriminating, non-correlating
      pendenticity based topochemical descriptor a was also conceptualized and
      successfully utilized for the development of a model for antitubercular activity
      of 5a-O-[(N-Acyl)sulfamoyl]adenosines. The proposed index exhibited not only high
      sensitivity towards both the presence as well as relative position(s) of
      pendent/heteroatom(s) but also led to significant reduction in degeneracy. Random
      forest correctly classified the analogues into active and inactive with an
      accuracy of 67.74%. A decision tree was also employed for determining the
      importance of molecular descriptors. The decision tree learned the information
      from the input data with an accuracy of 100% and correctly predicted the cross
      validated (10 fold) data with accuracy up to 77.4%. Statistical significance of
      proposed models was also investigated using intercorrelation analysis. Accuracy
      of prediction of proposed MAA models ranged from 90.4 to 91.6%.

PMID- 21179319
TI  - Determination of residual epichlorohydrin in sevelamer hydrochloride by static
      headspace gas chromatography with flame ionization detection.
AB  - A sensitive static headspace gas chromatographic method was developed and
      validated for the determination of residual epichlorohydrin (ECH) in sevelamer
      hydrochloride (SVH) drug substance. This method utilized a Phenomenex Zebron ZB
      WAX GC column, helium as carrier gas with flame ionization detection. The
      critical experimental parameters, such as, headspace vial incubation time and
      incubation temperature were studied and optimized. The method was validated as
      per United States Pharmacopoeia (USP) and International Conference on
      Harmonization (ICH) guidelines in terms of detection limit (DL), quantitation
      limit (QL), linearity, precision, accuracy, specificity and robustness. A linear
      range from 0.30 to 10 Ig/mL was obtained with the coefficient of determination
      (r(2)) 0.999. The DL and QL of ECH were 0.09 Ig/mL and 0.30 Ig/mL, respectively.
      The recovery obtained for ECH was between 91.7 and 96.6%. Also, the specificity
      of the method was proved through gas chromatography mass spectrometry (GC-MS).
      This method was applied successfully to determine the content of residual ECH in
      SVH bulk drug.

PMID- 21179320
TI  - Sensitive and rapid HPLC method for determination of memantine in human plasma
      using OPA derivatization and fluorescence detection: application to
      pharmacokinetic studies.
AB  - A rapid, sensitive and reproducible HPLC method was developed and validated for
      the analysis of memantine in human plasma after derivatization with o
      phthaldialdehyde (OPA) and fluorescence detection. Amantadine was used as
      internal standard. The derivatized memantine and amantadine were eluted in less
      than 10 min with no interference from endogenous plasma peaks. The analysis was
      carried out on a monolithic silica column (Chromolith Performance RP-18e, 100A4.6
      mm). The mobile phase was composed of a mixture of acetonitrile and 0.025 M
      phosphate buffer (50:50, v/v, pH=4.6) with a flow rate of 2.5 mLmin(a1). The
      excitation and emission wavelengths were set at 335 nm and 440 nm respectively.
      The assay enables the measurement of memantine for therapeutic drug monitoring
      with a lower quantification limit of 2 ngmL(a1). The method involves simple
      extraction procedure and analytical recovery was 82.8A 0.9%. The calibration
      curve was linear over the concentration range 2a80 ngmL(a1). The coefficients of
      variation for inter-day and intra-day assay were found to be less than 8%. The
      method was successfully applied to pharmacokinetic studies in humans.

PMID- 21179321
TI  - Development and validation of a stability-indicating RP-HPLC method for
      duloxetine hydrochloride in its bulk and tablet dosage form.
AB  - The objective of the present work was to develop a stability-indicating RP-HPLC
      method for duloxetine hydrochloride (DUL) in the presence of its degradation
      products generated from forced decomposition studies. The drug substance was
      found to be susceptible to stress conditions of acid hydrolysis. The drug was
      found to be stable to dry heat, photodegradation, oxidation and basic condition
      attempted. Successful separation of the drug from the degradation products formed
      under acidic stress conditions was achieved on a Hypersil C-18 column (250 mm A
      4.6 mm id, 5Im particle size) using acetonitrile: 0.01 M potassium dihydrogen
      phosphate buffer (pH 5.4 adjusted with orthophosphoric acid) (50:50, v/v) as the
      mobile phase at a flow rate of 1.0 ml/min. Quantification was achieved with
      photodiode array detection at 229 nm over the concentration range 1a25 Ig/ml with
      range of recovery 99.8a101.3 % for DUL by the RP-HPLC method. Statistical
      analysis proved the method to be repeatable, specific, and accurate for
      estimation of DUL. It can be used as a stability-indicating method due to its
      effective separation of the drug from its degradation products.

PMID- 21179322
TI  - Interaction of bioactive coomassie brilliant blue g with protein: insights from
      spectroscopic methods.
AB  - The binding of coomassie brilliant blue G (CBB) to bovine serum albumin (BSA) was
      investigated under simulative physiological conditions employing different
      optical spectroscopic techniques viz., fluorescence emission, UVavisible
      absorption and FTIR. Fluorescence quenching data obtained at different
      temperatures suggested the presence of dynamic type of quenching mechanism. The
      binding constant of CBB-BSA and the number of binding sites (n) for CBB in BSA
      were calculated and found to be 4.20 A 10(4) M(a1) and 0.96 respectively, at 302
      K. The value of n close to unity indicated that the protein has a single class of
      binding sites for CBB. The thermodynamic parameters revealed that the hydrophobic
      forces played a major role in the interaction of CBB to BSA. The distance between
      the CBB and protein was calculated using the theory of FAsteras Resonance Energy
      Transfer (FRET). The conformational change in the secondary structure of BSA upon
      interaction with dye was investigated by synchronous fluorescence and FTIR
      techniques. Competitive binding studies were also carried out to know the
      location of binding of CBB on BSA.

PMID- 21179323
TI  - Protective effect of L-carnitine and coenzyme Q10 on CCl4-induced liver injury in
      rats.
AB  - This study provides an information about the mechanisms of liver injury induced
      by CCl(4), and determines the influence of administration of L-carnitine or/and
      CoQ10 as prophylactic agents against CCl(4) deteriorative effect. The study was
      carried out on 80 adult male albino rats divided into eight groups, 10 animals
      each, as follows: four normal groups (control, treated with L-carnitine, treated
      with CoQ10, and treated with a combination of Lcarnitine and CoQ10) and four
      liver injury groups treated with CCl(4) (control, treated with L-carnitine,
      treated with CoQ10, and treated with a combination of L-carnitine and CoQ10).
      Liver injury was induced by s.c. injection of a single dose of CCl(4) (1 ml/kg).
      L-carnitine (50 mg/kg/day) was given i.p. for four successive days 24 hours
      before CCl(4) injection, and CoQ10 (200 mg/kg) was given as a single i.p. dose 24
      hours before CCl(4) injection. Animals were sacrificed 24 hours after CCl(4)
      injection, blood samples were withdrawn and liver tissue samples were
      homogenized. The levels of the following parameters were determined: hepatic
      reduced glutathione, serum ALT and AST, hepatic lipid peroxides, hepatic vitamin
      C, hepatic and serum total protein, serum albumin, serum sialic acid, serum
      nitrite, and serum and hepatic total LDH activities and LDH isoenzymes. The
      obtained data revealed that CCl(4) injection produced a significant decrease in
      reduced glutathione content, vitamin C, total protein and albumin levels.
      However, there was a significant increase in serum ALT and AST activities, lipid
      peroxides, sialic acid, nitric oxide, serum and hepatic total LDH activities. On
      the other hand, groups treated with L-carnitine or/and CoQ10 prior to CCl(4)
      injection showed an improvement in most parameters when compared with cirrhotic
      control group. It has been concluded that L-carnitine and coenzyme Q10 have a
      pronounced prophylactic effect against liver damage induced by halogenated
      alkanes such as carbon tetrachloride.

PMID- 21179324
TI  - Polyphenols from Ginkgo biloba.
AB  - By Sephadex LH-20 gel chromatography of an extract from Gingko biloba leaves,
      polymeric proanthocyanidins were eluted after the fractions of flavonol
      glycosides and biflavone glycosides. A purified proanthocyanidin polymer
      accounted for 86.6% of the total proanthocyanidins, and for 37.7% of the total
      antioxidant activity of this leaf extract. For structure elucidation, the polymer
      was submitted to acidic depolymerization in the presence of phloroglucinol. The
      structures of the resulting flavan-3-ols and phloroglucinol adducts were
      determined on the basis of 1D-and reverse 2D-NMR (HSQC, HMBC) spectra of their
      peracetylated derivatives, MALDI-TOF-MS and CD-spectroscopy. The observations
      resulting from the degradation with phloroglucinol were confirmed by (13)C-NMR
      spectroscopy of the polymer. The mean molecular weight of the polymeric fraction
      was estimated to be 9a10 flavan-3-ol-units.

PMID- 21179325
TI  - Development and evaluation of cefadroxil drug loaded biopolymeric films based on
      chitosan-furfural schiff base.
AB  - Cefadroxil drug loaded biopolymeric films of chitosan-furfural schiff base were
      prepared by reacting chitosan with furfural in presence of acetic acid and
      perchloric acid respectively for the external use. Prepared films were evaluated
      for their strength, swelling index, thickness, drug content, uniformity, tensile
      strength, percent elongation, FTIR spectral analysis and SEM. The results of in
      vitro diffusion studies revealed that the films exhibited enhanced drug diffusion
      as compared to the films prepared using untreated chitosan. The films also
      demonstrated good to moderate antibacterial activities against selective gram
      positive and gram negative bacteria.

PMID- 21179326
TI  - Floating matrix dosage form for propranolol hydrochloride based on gas formation
      technique: development and in vitro evaluation.
AB  - Gastroretentive tablets of propranolol hydrochloride were developed by direct
      compression method using citric acid and sodium bicarbonate as the effervescent
      base. Hydroxypropyl methylcellulose; HPMC K15M was used to prepare the floating
      tablets to retard the drug release for 12h in stomach. Na-carboxymethyl cellulose
      (NaCMC) or carbopol 934P was added to alter the drug release profile or the
      dimensional stability of the formulation. Dicalcium phosphate (DCP) was used as
      filler. Formulations were evaluated for floating lag time, duration of floating,
      dimensional stability, drug content and in vitro drug release profile. The
      formulations were found to have floating lag time less than 1min. It was found
      that the dimensional stability of the formulations increase with increasing
      concentration of the swelling agent. The release mechanism of propranolol
      hydrochloride from floating tablets was evaluated on the basis of Peppas and
      Higuchi model. The ana value of the formulations ranged from 0.5201 to 0.7367
      (0.5<n<1.0) which indicated anomalous (non-Fickian) transport mechanism.
      Formulation containing 27.5% HPMC K15M, 29% DCP, 3.75% citric acid and 18.75%
      sodium bicarbonate seemed most desirable. FTIR, DSC and XRPD studies indicated
      the absence of any significant chemical interaction within dug and excipients.
      Stability study of optimized formulation revealed no significant change and found
      to be stable.

PMID- 21179327
TI  - Sodium alginate based mucoadhesive system for gatifloxacin and its in vitro
      antibacterial activity.
AB  - The objective of this study was to formulate sodium alginate based ophthalmic
      mucoadhesive system of gatifloxacin and its in vitro antibacterial potential on
      pathogenic microorganisms, Staphylococcus aureus and Escherichia coli. Sodium
      carboxymethylcellulose (NaCMC) was added to the formulations to enhance the gel
      bioadhesion properties. The prepared formulations were evaluated for their in
      vitro drug release, gelation behaviour, rheological behavior, and mucoadhesion
      force. All formulations in non-physiological and physiological condition showed
      pseudo plastic behavior. Increase in the concentration of sodium alginate and
      sodium CMC enhanced the mucoadhesive force significantly. In vitro release of
      gatifloxacin from the system in simulated tear fluid (STF, pH a 7.4), was
      influenced significantly by the properties and concentration of sodium alginate,
      NaCMC. Significant reduction in total bacterial count was observed between
      control and treatment groups with both the test organisms.

PMID- 21179328
TI  - Carbopol/chitosan based pH triggered in situ gelling system for ocular delivery
      of timolol maleate.
AB  - The poor bioavailability and therapeutic response exhibited by conventional
      ophthalmic preparations due to rapid precorneal elimination, dilution and
      nasolacrimal drainage of the drug may be vanquished by the use of in situ gelling
      systems that are instilled as drops in to the eye and undergo a sol-gel
      transition in the cul-de-sac. Timolol eye drops may cause systemic side effects
      in glaucoma patients due to absorption of the drug into systemic circulation. In
      situ gelling system of this drug can provide localized effect with reduced
      contraindications, improved patient compliance and better therapeutic index. The
      present work describes the formulation and evaluation of an ophthalmic delivery
      system of an antiglaucoma drug, timolol maleate (TM) based on the concept of pH
      triggered in situ gelation. Polyacrylic acid (carbopol) was used as the gelling
      agent in combination with chitosan (amine polysaccharide), which was acted as a
      viscosity-enhancing agent. Formulations were evaluated for pH, viscosity, gelling
      capacity and drug content. The 0.4% w/v carbopol/0.5% w/v chitosan based in situ
      gelling system was in liquid state at room temperature and at the pH formulated
      (pH 6.0) and underwent rapid transition into the viscous gel phase at the pH of
      the tear fluid (lacrimal fluid) (pH 7.4). The in vitro drug release and in vivo
      effects of the developed in situ gelling system were compared with that of
      GlucomolA (a 0.25% TM ophthalmic solution), 0.4% w/v carbopol solution as well as
      liposomal formulation. The results clearly demonstrated that developed carbopol
      chitosan based formulation was therapeutically efficacious and showed a fickian
      (diffusion controlled) type of release behaviour over 24 h periods. The developed
      system is thus a viable alternative to conventional eye drops and can also
      prevent the rapid drainage as in case of liposomes.

PMID- 21179329
TI  - Permeability evaluation through chitosan membranes using taguchi design.
AB  - In the present study, chitosan membranes capable of imitating permeation
      characteristics of diclofenac diethylamine across animal skin were prepared using
      cast drying method. The effect of concentration of chitosan, concentration of
      cross-linking agent (NaTPP), crosslinking time was studied using Taguchi design.
      Taguchi design ranked concentration of chitosan as the most important factor
      influencing the permeation parameters of diclofenac diethylamine. The flux of the
      diclofenac diethylamine solution through optimized chitosan membrane (T9) was
      found to be comparable to that obtained across rat skin. The mathematical model
      developed using multilinear regression analysis can be used to formulate chitosan
      membranes that can mimic the desired permeation characteristics. The developed
      chitosan membranes can be utilized as a substitute to animal skin for in vitro
      permeation studies.

PMID- 21179330
TI  - Quality of life of women with urinary incontinence: a systematic literature
      review.
AB  - PURPOSE: The purpose of this study was to review studies that have examined the
      quality of life of women with urinary incontinence. MATERIALS AND METHODS: A
      review was conducted that used the databases PubMED, Proquest, CINAHL, and
      Sciencedirect. Articles were included that were published in English between 2005
      and 2010 the key words use were urinary incontinence, women, and quality of life.
      RESULTS: A total of 18 studies were identified, and the prevalence of urinary
      incontinence varied depending on the definition of incontinence used and the age
      of the population studied. The Incontinence Quality of Life (I-QoL), Incontinence
      Impact Questionnaire-short form (IIQ-7), and King's Health Questionnaire (KHQ)
      were the most commonly used instruments. Demographic, medical, physical,
      psychological, health, and intervention factors were reported as influencing
      factors on the quality of life of women with incontinence. Age, severity of
      urinary incontinence, type of urinary incontinence, number of urinary
      incontinence episodes, body weight, stress, and help-seeking behavior were
      statistically significant variables influencing quality of life. CONCLUSION:
      Future studies are needed to identify factors related to quality of life among
      women with incontinence and to use validated instruments according to specific
      subjects.

PMID- 21179331
TI  - Effect of Treadmill Exercise on Leak-point pressure and Neuronal Activation in
      Brain of Rats with Stress Urinary Incontinence.
AB  - PURPOSE: Stress urinary incontinence (SUI) commonly occurs in women, and it
      causes enormous impact on quality of life. Surgery, drugs, and exercise have been
      recommended for the treatment of this disease. Among these exercise is also known
      to be effective for relieving thesymptoms of SUI, however, the efficacy and
      underlying mechanisms of exercise on SUI are poorly understood. In the present
      study, we investigated the effect of treadmill exercise on abdominal leak-point
      pressure and neuronal activity in the medial preoptic nucleus (MPA),
      ventrolateral periaqueductal gray (vlPAG), and pontine micturition center (PMC)
      following urethrolysis in rats. MATERIALS AND METHODS: Adult female Sprague
      Dawley rats, weighing 250+/-10 g (9 weeks old), were used in this study. After
      having undergone transabdominal urethrolysis to induce SUI, the rats were divided
      into three groups (n=6 in each group): a sham operation group, an SUI-induced
      group, and an SUI-induced and treadmill exercise group. The rats in the exercise
      group performed treadmill running for 30 min once a day starting 2 weeks after
      the induction of SUI and continuing for 4 weeks after surgery. For this study,
      determination of abdominal leak point pressure and immunohistochemistry for c-Fos
      in the brain were performed. RESULTS: Induction of transabdominal urethrolysis
      significantly reduced the abdominal leak point pressure, thereby contributing to
      the induction of SUI. In contrast, abdominal leak point pressure was
      significantly improved by treadmill exercise. The expression of c-Fosin the MPA,
      vlPAG, and PMC, the brain areas relating to micturition, was enhanced by the
      induction of SUI, whereas treadmill exercise significantly suppressed SUI-induced
      c-Fos expression, suggesting that neuronal activation in the micturition centers
      was suppressed by treadmill exercise. CONCLUSION: The present results suggest
      that treadmill exercise may be an effective therapeutic modality for ameliorating
      the symptoms of SUI.

PMID- 21179332
TI  - Expression of nitric oxide synthase and aquaporin-3 in cyclophosphamide treated
      rat bladder.
AB  - PURPOSE: The expression of Nitric oxide Synthase (NOS) and aquaporin (AQP) water
      channels in rat bladder is recently reported. The aim of this study is to
      evaluate the expression of inducible NOS (iNOS), aquaporin-3 (AQP-3) in
      cyclophosphamide (CYP) induced rat bladder. MATERIALS AND METHODS: The 32 Sprague
      Dawley rats were divided into cystitis group (n=20) and control group (n=12). In
      cystitis group, 100mg/kg CYP was injected every second day for 1 week whereas in
      control group, normal saline was injected. After extracting of the bladder and
      dividing dome, body and trigone of the bladder, independently H&E staining and
      immunohistochemical staining for iNOS and AQP-3 were performed. Expressions of
      iNOS and AQP-3 were analyzed with a confocal laser scanning microscope and an
      image analyzer. RESULTS: The expression of iNOS significantly increased in the
      mucosa, submucosa layer of dome in cystitis group (p<0.05). The expression of AQP
      3 significantly increased in the mucosa, submucosa, vessel layer of dome in
      cystitis group (p<0.05). CONCLUSIONS: These results suggest that inflammatory
      change activates NOS and AQP-3 expression in the bladder tissue of rats. These
      may imply that NOS and AQP-3 have a pathophyiological role in the cyclophophamide
      induced interstitial cystitis. Further study on the NOS and AQP-3 in bladder is
      needed for clinical application.

PMID- 21179333
TI  - Changes in Awake Cystometry and Expression of Bladder beta-adrenoceptors after
      Partial Bladder Outlet Obstruction in Male Rats.
AB  - PURPOSE: To explore possible changes in awake cystometry and expression of beta
      adrenoceptors (ARs) as a cause for bladder dysfunction in a male rat model of
      partial bladder outlet obstruction (pBOO). MATERIALS AND METHODS: Awake
      cystometry was performed in rats with pBOO (16) and sham-operated rats (16), 8
      weeks after the operation. The expression of mRNA and protein of beta-ARs was
      assessed by real-time PCR and western blot. RESULTS: The bladders with pBOO
      (1030mg) were increased compared to those in control rats (230mg). In the
      cystometric studies, the maximum intravesical pressure significantly increased in
      the pBOO group compared to control group rats (p=0.001). The time to reach
      maximal intravesical pressure during micturition in the pBOO group was
      significantly longer than the sham group (p=0.003). The frequency of non-void
      contraction in the pBOO group was significantly more than the sham group
      (p=0.006). The mRNA expressions of beta2- and 3-ARs were increased
      insignificantly in pBOO group compared to sham group. The data of pBOO group
      expressed as folds of corresponding expression in sham group were 1.28 and 1.46
      respectively in beta2- and 3-ARs. Compared to the sham groups, the density of
      60Kda protein band recognized by beta2-AR antibodies and the density of 45Kda
      protein band recognized by beta3-AR antibodies were higher in the bladder from
      pBOO group rats. CONCLUSION: PBOO of male rats increase the maximal intravesical
      pressure and contraction time during micturition and the frequency of non-void
      contraction as well as weight of bladder. The expression of beta2- and 3-ARs
      subtypes was increased insignificantly compared to sham operated group. This
      study demonstrates that the changes of cystometric or non-void contraction
      parameters in pBOO is one of the pathophysiologic processes potentially
      associated with the alterations of bladder beta-ARs.

PMID- 21179334
TI  - Tape Shortening for Recurrent Stress Urinary Incontinence After Transobturator
      Tape Sling: 3-Year Follow-up Results.
AB  - PURPOSE: Recently, as the number of transobturator tape (TOT) procedures has
      increased, recurrence after this procedure has been frequently reported. However,
      there are no standard guidelines for treatment. We describe our experience with
      shortening the previously implanted tape in patients with recurrent stress
      urinary incontinence after the TOT procedure. MATERIALS AND METHODS: We enrolled
      10 women who underwent shortening of the previously implanted tape and were
      followed up for 3 years. Shortening of the previously implanted tape was done by
      a figure-eight suture with 1-0 Prolene. One year after TOT shortening, we
      investigated continence status, patient satisfaction by means of a questionnaire,
      maximal flow rate (Qmax), and postvoid residual urine volume. Three years after
      TOT shortening, we evaluated continence status and patient satisfaction. RESULTS:
      The mean period of TOT shortening was 4.2 months (range, 1-12 months) after the
      TOT procedure. One year after TOT shortening, 7 patients showed complete dryness,
      2 patients showed improvement, and 1 patient reported failure. Eight patients
      were very satisfied or satisfied with the 1-year result after TOT shortening. The
      mean preoperative and postoperative Qmax were 23.8 and 26.7ml/s, respectively,
      and there was no significant difference. Three years after TOT shortening, 6
      patients showed complete dryness, 2 patients showed improvement, and 2 patients
      reported failure. Among them,1 had failed from 1 year after TOT shortening and
      the other had shown 1 year of complete dryness. Eight patients were very
      satisfied or satisfied and 2 patients were dissatisfied with the 3-year result
      after TOT shortening. CONCLUSION: Most of the patients who underwent TOT
      shortening reported satisfaction as well as improvement of incontinence after a 3
      year follow up. Therefore, we suggest that TOT shortening may be recommended
      primarily in patients with recurrent stress urinary incontinence after the TOT
      sling procedure.

PMID- 21179335
TI  - Changes in Sexual Function after the Midurethral Sling Procedure for Stress
      Urinary Incontinence: Long-term Follow-up.
AB  - PURPOSE: It is known that 50% to 68% of women with stress urinary incontinence
      (SUI) have sexual function impairment and avoid sexual intercourse. Reports of
      sexual function after SUI surgery vary, with reports of both improved function
      and deteriorated function. The goal of this study was to evaluate the impact of
      midurethral sling procedures on the sexual function of women suffering from SUI
      preoperatively and 36 months postoperatively. MATERIALS AND METHODS: Among 75
      patients who were diagnosed with SUI and underwent the midurethral procedure, 47
      patients who answered the Korean version of the Female Sexual Function Index
      (FSFI) Questionnaire were analyzed prospectively. The retropubic route (RPR) was
      used in 26 patients, whereas the transobturator route (TOR) was used in 21
      patients. Fifteen patients underwent concomitant posterior colporrhaphy. The FSFI
      was completed before surgery and 36 months after surgery. RESULTS: The patients'
      mean age was 44.9 years (range, 30-59 years) and their mean parity was 2.8
      (range, 0-6). There were no significant differences in the individual FSFI domain
      scores between before surgery and 36 months (36.8+/-4.57) after surgery. There
      were no significant differences in sexual satisfaction between the patients with
      concomitant posterior colporrhaphy and patients with the midurethral sling
      procedure only. There were no significant differences in domain score between the
      TOR and the RPR, but patients experienced less pain after the RPR than after the
      TOR. CONCLUSION: There was no significant change in overall sexual function in
      women undergoing the midurethral sling procedure. Attention must be paid when
      performing the TOR procedure because it can cause pain during intercourse.

PMID- 21179336
TI  - The effect of posterior colporrhaphy performed concurrently with midurethral
      sling surgery on the sexual function of women with stress urinary incontinence.
AB  - PURPOSE: Some women choose to undergo posterior colporrhaphy (PC) concurrently
      with procedures for SUI to regain sexual confidence and improve sexual function.
      We determine the effect of PC on sexual function in women requiring a midurethral
      sling for SUI. MATERIALS AND METHODS: A total of 119 women were retrospectively
      reviewed 81 women had the midurethral sling alone (Group A), and 38 women
      voluntarily had PC concurrently with the midurethral sling (Group B). Sexual
      function was evaluated using the FSFI before and after surgery. RESULTS: THE
      POSTOPERATIVE COMPOSITE SCORES WERE SIGNIFICANTLY INCREASED IN BOTH GROUPS (GROUP
      A: p=0.02; Group B: p=0.04), and significant increases were observed in 'desire,'
      'arousal' and 'satisfaction'. However, there were no significant differences in
      the composite score or six domainscores between the two groups. CONCLUSION: PC
      performed concurrently with midurethral sling for treatment of SUI does not
      provide any additional benefits towards improving the sexual function.

PMID- 21179337
TI  - Acute and serious myositis with abscess in thigh muscle after transobturator tape
      implantation.
AB  - The complications of transobturator tape (TOT) were known as lower urinary tract
      injury, postoperative urinary retention, urge incontinence, vaginal erosion, and
      etc. A 63-year-old woman presented with new onset of severe pain, heating, and
      swelling of the left thigh and perineum. She had undergone TOT implantation for
      stress urinary incontinence (SUI) 4 days previously in an outside clinic. Painful
      left thigh swelling and skin erythema were noted on the physical examination. A
      computed tomography (CT) scan showed multiple, large left medial thigh and
      obturator abscesses. Removal of the implanted tape and abscess drainage were
      performed immediately and two additional operations were needed for proper
      abscess drainage. We believe this case to be one of the most serious
      complications to occur since the introduction of the TOT procedure. Here we
      report this case and discuss its initial management along with a review of the
      literature.

PMID- 21179338
TI  - Unusual foreign bodies in the urinary bladder and urethra due to autoerotism.
AB  - Most foreign bodies in the lower genitourinary tract are self-inserted via the
      urethra as the result of exotic impulses, psychometric problems, sexual
      curiosity, or sexual practice while intoxicated. Diagnosis of these foreign
      bodies can be done by clinical history, physical examination, and image studies
      of the patient. The treatment of foreign bodies is determined by their size,
      location, shape, and mobility. In most cases, minimally invasive procedures such
      as endoscopic removal are recommended to prevent bladder and urethral injuries.
      In some cases, however, surgical treatment should be done if the foreign bodies
      cannot be removed by the endoscopic procedure or further injuries are expected as
      a result of the endoscopic procedures. Herein we present 2 cases of self-inserted
      lower genitourinary foreign bodies with a brief review of the literature.

PMID- 21179339
TI  - Acute administration of clozapine and risperidone altered dopamine metabolism
      more in rat caudate than in nucleus accumbens: a dose-response relationship.
AB  - The present study compares the extrapyramidal and neurochemical effects of
      clozapine and risperidone in rat caudate (corpus striatum) and nucleus accumbens
      (ventral striatum) dose-dependently. Animals injected with clozapine (2.5, 5.0
      and 10.0 mg/kg IP) or risperidone (1.0, 2.5 and 5.0 mg/kg IP) in acute were
      sacrificed 1 h later to collect brain samples. Extrapyramidal side effects (EPS)
      in terms of locomotor activity and catalepsy were monitored in each animal after
      the drug or vehicle administration. Maximum cataleptic potentials were found only
      at high doses of clozapine (10.0 mg/kg; 60%) and risperidone (5.0 mg/kg; 100%).
      Neurochemical estimations were carried out by HPLC-EC. Both drugs at all doses
      significantly (p<0.01) increased the concentration of homovanillic acid (HVA), a
      metabolite of DA, in the caudate nucleus and decreased in nucleus accumbens.
      Levels of Dihydroxyphenylacetic acid (DOPAC) significantly (p<0.01) increased in
      the caudate by clozapine administration and decreased in the nucleus accumbens by
      the administration of both drugs in a dose-dependent manner. 5
      Hydroxyindoleacetic acid (5-HIAA), the predominant metabolite of serotonin
      significantly decreased in the caudate and nucleus accumbens in a similar
      fashion. Levels of tryptophan (TRP) were remained insignificant in caudate and
      nucleus accumbens by the injections of two drugs. In caudate, clozapine and
      risperidone administrations significantly (p<0.01) decreased HVA/DA ratio and
      increased DOPAC/DA ratio in nucleus accumbens at all doses. The findings suggest
      the evidence for DA/5-HT receptor interaction as an important link in the lower
      incidence of EPS. The possible role of serotonin(1A) receptors in the
      pathophysiology of schizophrenia is also discussed.

PMID- 21179340
TI  - Oleuropein in olive and its pharmacological effects.
AB  - Olive from Olea europaea is native to the Mediterranean region and, both the oil
      and the fruit are some of the main components of the Mediterranean diet. The main
      active constituents of olive oil include oleic acid, phenolic constituents, and
      squalene. The main phenolic compounds, hydroxytyrosol and oleuropein, give extra
      virgin olive oil its bitter, pungent taste. The present review focuses on recent
      works that have analyzed the relationship between the major phenolic compound
      oleuropein and its pharmacological activities including antioxidant, anti
      inflammatory, anti-atherogenic, anti-cancer activities, antimicrobial activity,
      antiviral activity, hypolipidemic and hypoglycemic effect.

PMID- 21179342
TI  - Synthesis and antimicrobial activity of 3-(1,3,4-Oxadiazol-2-yl)quinazolin-4(3H)
      ones.
AB  - In attempt to find new pharmacologically active molecules, we report here the
      synthesis and in vitro antimicrobial activity of various 3-(1,3,4-oxadiazol-2-yl)
      quinazolin-4(3H)-ones. The antimicrobial activity of title compounds were
      examined against two gram positive bacteria (S. aureus, S. pyogenes), two gram
      negative bacteria (E. coli, P. aeruginosa) and three fungi (C. albicans, A.
      niger, A. clavatus) using the broth microdilution method. Some derivatives
      bearing a bromo or iodo group exhibited very good antimicrobial activity.

PMID- 21179341
TI  - Antidepressant/anxiolytic and anti-nociceptive effects of novel 2-substituted 1,4
      benzodiazepine-2-ones.
AB  - Oxazepam (4a) has been used as overall starting material in the synthesis of
      novel 2-substituted 1,4-benzodiazepines.By reacting Oxazepam 4a with commercially
      available hydrazines, hydrazides, semicarbazide, aminoguanidine and N,N
      dimethylamino aniline in ethanol under acetic conditions, a series of diazenyl
      1,4-benzodiazepines 5aa5i and 2-amino-1,4-benzodiazepine 5k were obtained in good
      yields.These novel compounds served as new chemical entities (NCE) for testing in
      mice. The diazo-benzodiazepine 5d has shown a promising antidepressant effect in
      initial experiments in vivo at a dose of 5 mg/kg. The highly coloured 2
      aminobenzodiazepine derivative 5k showed over a dose range from 5a50 mg/kg an
      analgesic effect in mice.

PMID- 21179343
TI  - Pharmacophore elucidation and molecular docking studies on 5-phenyl-1-(3-pyridyl)
      1h-1,2,4-triazole-3-carboxylic acid derivatives as COX-2 inhibitors.
AB  - A set of 5-phenyl-1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic acid derivatives
      (16a32) showing anti-inflammatory activity was analyzed using a three-dimensional
      qualitative structure-selectivity relationship (3D QSSR) method. The
      CatalystHipHop approach was used to generate a pharmacophore model for
      cyclooxygenase-2 (COX-2) inhibitors based on a training set of 15 active
      inhibitors (1a15). The degree of fitting of the test set compounds (16a32) to the
      generated hypothetical model revealed a qualitative measure of the more or less
      selective COX-2 inhibition of these compounds. The results indicate that most
      derivatives (16, 18, 20a25, and 30a32) are able to effectively satisfy the
      proposed pharmacophore geometry using energy accessible conformers (E(conf) < 20
      kcal/mol). In addition, the triazole derivatives (16a32) were docked into COX-1
      and COX-2 X-ray structures, using the program GOLD. Based on the docking results
      it is suggested that several of these novel triazole derivatives are active COX
      inhibitors with a significant preference for COX-2. In principle, this work
      presents an interesting, comprehensive approach to theoretically predict the mode
      of action of compounds that showed anti-inflammatory activity in an in vivo
      model.

PMID- 21179344
TI  - Evaluation of the pharmaceutical quality of docetaxel injection using new
      stability indicating chromatographic methods for assay and impurities.
AB  - New stability indicating chromatographic methods have been developed for
      estimation of Assay and Impurities of Docetaxel in Docetaxel injection for
      evaluation of pharmaceutical quality. With this method, the process related
      impurities and degradants are well separated from the peaks due to placebo. The
      relative retention times and relative response factors of the known impurities
      have been established. The LOQ of the known impurities and docetaxel are found to
      be less than 0.2 Ig /ml and the recovery falls in the range of 90a110%. Peak
      purities demonstrated the stability indicating nature of the methods. The methods
      developed in the present study overcome the lacunae of the existing published
      methodologies in evaluation of the quality of Docetaxel injection. In essence,
      the present study provides an improved methodology for evaluation of the
      pharmaceutical quality of Docetaxel injection.

PMID- 21179345
TI  - 3D-QSAR design of new escitalopram derivatives for the treatment of major
      depressive disorders.
AB  - Antidepressants are psychiatric agents used for the treatment of different types
      of depression being at present amongst the most commonly prescribed drug, while
      their effectiveness and adverse effects are the subject of many studies and
      competing claims. Having studied five QSAR models predicting the biological
      activities of 18 antidepressants, already approved for clinical treatment, in
      interaction with the serotonin transporter (SERT), we attempted to establish the
      membrane ionsa contributions (sodium, potassium, chlorine and calcium) supplied
      by donor/acceptor hydrogen bond character and electrostatic field to the
      antidepressant activity. Significant cross-validated correlation q(2) (0.5a0.6)
      and the fitted correlation r(2) (0.7a0.82) coefficients were obtained indicating
      that the models can predict the antidepressant activity of compounds. Moreover,
      considering the contribution of membrane ions (sodium, potassium and calcium) and
      hydrogen bond donor character, we have proposed a library of 24 new escitalopram
      structures, some of them probably with significantly improved antidepressant
      activity in comparison with the parent compound.

PMID- 21179346
TI  - Simultaneous determination of different polyamines and their mono-acetylated
      derivatives in gastric tissue by HPLC with post-column derivatization.
AB  - A simple and highly sensitive procedure is described enabling the simultaneous
      determination of biogenic polyamines (PAs) and their related monoacetyl
      derivatives in stomach tissue. The method is based on HPLC using octane sulfonate
      as an ion-pairing agent employed in acetate buffers at pH 4.5. The application is
      accompanied with fluorescence detection followed by post-column derivatization
      with o-phthaldialdehyde at room temperature (20A0.5AC). N(1)- and N(8)
      acetylspermidines (ASPD) can be determined with this method in the same run
      without performing any special procedures or pre-purification in concentrations
      exceeding 8.5 pmoles. The variability in reproducibility of the day-today
      precision and duplicate determination, and simultaneous determination of standard
      mixture and biological samples were found < 2%. The mean (A s.e.mean) retention
      times (n=12) for putrescine (Put), N(1)-ASPD, N(8)-ASPD, spermidine (Spd) and
      spermine (Spm) are 8.97A0.025; 17.64A0.063; 18.99A0.133; 28.20A0.070 and
      39.81A0.098 min, respectively. The method was applied to determine PAs and
      specifically N(1)- and N(8)-ASPD in glandular part of stomach tissue of fasting
      rats (STFR) without any interference with endogenous aminoacids, histamine, and
      other reactive moieties. PAs and both mono-ASPD have been successfully determined
      in the STFR and the values are as follows: Put 37.2A10.1; N(1)-ASPD 5.88A0.48;
      N(8)-ASPD 4.43A0.94; Spd 750.7A22.7 and Spm 618.2A37.4 nmole/g of wet tissue.
      Information on gastric tissue polyamines and their acetylated derivatives may be
      useful in understanding the mechanism of drugs or agents that play some part in
      gastric ulcer production or its repair mechanisms.

PMID- 21179347
TI  - Traditional medicine in the pristine village of ProkoAko Lake on Vranica
      Mountain, Bosnia and Herzegovina.
AB  - The results of an ethnobotanical study conducted in the pristine village of
      ProkoAko Lake (Vranica Mountain, Bosnia and Herzegovina) in summer 2007 is
      presented. Informal interviews involving 12 informants known as atraditional
      healersa provided data from 43 plants used in 82 prescriptions. The applied
      plants were used for a broad spectrum of indications. The most frequent were
      gastro-intestinal tract ailments, blood system disorders, skin ailments,
      respiratory tract ailments and urinary-genital tract ailments. The most frequent
      preparation was an infusion. Other often used preparations were ointments or
      balms and decocts. The special Bosnian balms known as amehlemsa were prepared
      from freshly chopped or freshly pressed herbal parts of various plant species.
      Warmed resins from Abies or Picea species, raw cow or pig lard, olive oil and
      honey served as basis. The traditional doctors, who usually worked as a team,
      enjoyed such a good reputation that people from all over the country were
      visiting in search of alternative ways to cure their ailments and diseases. The
      practical techniques applied by the healers and some of their attitudes and
      values are reported.

PMID- 21179348
TI  - Formulation and in vitro evaluation of rifampicin loaded porous microspheres.
AB  - Rifampicin (RIF) is a major component in fixed dose combination therapy for the
      treatment of tuberculosis. RIF has low solubility and high permeability with high
      dose and hence it is classified as class II drug in Biopharmaceutical
      Classification System (BCS). RIF has poor and variable bioavailability because of
      its poor solubility, acid decomposition and, drug and food interaction. The
      present investigation was aimed to develop RIF loaded porous microspheres as a
      controlled release dosage form. Eudragit based porous microspheres of RIF were
      prepared by emulsion solvent diffusion method. Prepared porous microspheres were
      evaluated for its entrapment efficacy, morphology, thermal behavior, crystalline
      nature, in-vitro drug release and stability in simulated gastric fluid. The
      entrapment efficacy of drug loaded microspheres was found to be in the range of
      19.04a74.57%. Surface morphology revealed the porous and spherical structure of
      microspheres. Differential scanning calorimetric studies confirmed that
      formulation process altered the crystalline nature of RIF. In vitro drug release
      studies indicated that drug to polymer ratio of 2:1 showed more than 85% drug
      release over the period of 3 h. Stability studies in simulated gastric fluid
      (SGF) indicated that low relative decomposition of 18.5% was achieved with high
      drug to low polymer ratio of 1:4. The results obtained from the present
      investigation concluded that RIF loaded porous microspheres are suitable for
      developing oral controlled release dosage form of RIF that can prevent acid
      decomposition and provide better biopharmaceutical properties. Further more the
      microspheres can be evaluated for preventing the interaction with isoniazid,
      other drugs and foodstuffs.

PMID- 21179349
TI  - Formulation optimization of hydrodynamically balanced oral controlled release
      bioadhesive tablets of tramadol hydrochloride.
AB  - The directly compressible floating-bioadhesive tablets of tramadol were
      formulated using varying amounts Carbopol 971P (CP) and hydroxy-propylmethyl
      cellulose (HPMC), along with other requisite excipients. In vitro drug release
      profile, floatational characteristics and ex vivo bioadhesive strength using
      texture analyzer were determined, and systematically optimized using a 3(2)
      central composite design (CCD). The studies indicated successful formulation of
      gastroretentive compressed matrices with excellent controlled release,
      mucoadhesion and hydrodynamic balance. Comparison of the dissolution profiles of
      the optimized formulation, with optimal composition of CP:HPMC :: 80.0:125.0,
      with that of the marketed controlled release formulation other indicated analogy
      of drug release performance with each other. Validation of optimization study
      using eight confirmatory experimental runs indicated very high degree of
      prognostic ability of CCD with mean A SEM of a0.06% A 0.37. Further, the study
      successfully unravels the effect of the polymers on the selected response
      variables.

PMID- 21179350
TI  - Liquisolid systems to improve the dissolution of furosemide.
AB  - A liquisolid system has the ability to improve the dissolution properties of
      poorly water soluble drugs. Liquisolid compacts are flowing and compactable
      powdered forms of liquid medications. The aim of this study was to enhance the in
      vitro dissolution properties of the practically water insoluble loop diuretic
      furosemide, by utilising liquisolid technique. Several liquisolid tablets were
      prepared using microcrystalline cellulose (AvicelA pH-101) and fumed silica (Cab
      O-SilA M-5) as the carrier and coating materials, respectively. Polyoxy-ethylene
      polyoxypropylene-polyoxyethylene block copolymer (SynperonicA PE/L 81); 1,2,3
      propanetriol, homopolymer, (9Z)-9-octadecenoate (CaprolA PGE-860) and
      polyethylene glycol 400 (PEG 400) were used as non- volatile water-miscible
      liquid vehicles. The liquid loading factors for such liquid vehicles were
      calculated to obtain the optimum amounts of carrier and coating materials
      necessary to produce acceptable flowing and compactible powder admixtures viable
      to produce compacts. The ratio of carrier to coating material was kept constant
      in all formulations at 20 to 1. The formulated liquisolid tablets were evaluated
      for post compaction parameters such as weight variation, hardness, drug content
      uniformity, percentage friability and disintegration time. The in-vitro release
      characteristics of the drug from tablets formulated by direct compression (as
      reference) and liquisolid technique, were studied in two different dissolution
      media. Differential scanning calorimetry (DSC) and Fourier-Transform infrared
      spectroscopy (FT-IR) were performed. The results showed that all formulations
      exhibited higher percentage of drug dissolved in water (pH 6.4a6.6) compared to
      that at acidic medium (pH 1.2). Liquisolid compacts containing SynperonicA PE/L
      81 demonstrated higher release rate at the different pH values. Formulations with
      PEG 400 displayed lower drug release rate, compared to conventional and
      liquisolid tablets. DSC and FT-IR indicated a possible interaction between
      furosemide and tablet excipients that could explain the dissolution results.
      CaprolA PGE-860, as a liquid vehicle, failed to produce furosemide liquisolid
      compacts.

PMID- 21179351
TI  - Cyclosporine a-nanosuspension: formulation, characterization and in vivo
      comparison with a marketed formulation.
AB  - Cyclosporine A-nanosuspensions were prepared using zirconium oxide beads as a
      milling media, Poloxamer 407 as a stabilizer and distilled water as an aqueous
      medium using the Pearl Milling technique. The optimized formulation was
      characterized in terms of particle size distribution, surface morphology, drug
      surfactant interaction, drug content, saturation solubility, osmolarity, and
      stability. The nanoparticles consisting of Poloxamer-bound cyclosporin A with a
      mean diameter of 213 nm revealed a spherical shape and 5.69 fold increased
      saturation solubility as compared to the parent drug. The formulation was found
      to be iso-osmolar with blood and stable up to 3 months at 2a8AC. In-vivo studies
      were carried out in albino rats and the pharmacokinetic parameters were compared
      with a marketed formulation, which indicated better results of the prepared
      formulation than the marketed one.

PMID- 21179352
TI  - Preparation and in vitro/in vivo characterization of porous sublingual tablets
      containing ternary kneaded solid system of vinpocetine with i-cyclodextrin and
      hydroxy Acid.
AB  - The demand for sublingual tablets has been growing during the previous decades
      especially for drugs with extensive hepatic first-pass metabolism. Vinpocetine, a
      widely used neurotropic agent, has low oral bioavailability due to its poor
      aqueous solubility and marked first-pass metabolism. Accordingly, the aim of this
      work was to develop tablets for the sublingual delivery of vinpocetine.
      Initially, the feasibility of improving vinpocetineas poor aqueous solubility by
      preparing kneaded solid systems of the drug with I-Cyclodextrin and hydroxy acids
      (citric acid and tartaric acid) was assessed. The solid system with improved
      solubility and dissolution properties was incorporated into porous tablets that
      rapidly disintegrate permitting fast release of vinpocetine into the sublingual
      cavity. The pores were induced into these tablets by directly compressing the
      tabletsa excipients with a sublimable material, either camphor or menthol, which
      was eventually sublimated leaving pores. The obtained results demonstrated that
      the tablets prepared using camphor attained sufficient mechanical strength for
      practical use together with rapid disintegration and dissolution. In vivo
      absorption study performed in rabbits indicated that the sublingual
      administration of the proposed porous tablets containing vinpocetine solid system
      with I-Cyclodextrin and tartaric acid could be useful for therapeutic
      application.

PMID- 21179353
TI  - Austrian pharmacy in the 18 and 19th century.
AB  - This overview reflects the extensive changes in the health care system which had
      significant effects on the apothecaryas profession and education. In the 18(th)
      century Maria Theresia assigned Gerard van Swieten to modernize the medical
      curriculum and to work out reforms for health care. The resulting sanitary bill
      released in 1770 and amended in 1773 became effective for the whole empire and
      influenced greatly the apothecaryas profession. The Viennese Medical Faculty
      continued to be the supervisory body for the apothecaries, a situation which
      prolonged the conflicts between the faculty and the apothecaries. The financial
      and social distress prevalent in the 19(th) century also affected the apothecary
      business and led to a crisis of the profession. Furthermore, the apothecariesa
      missing influence over the sanitary authorities delayed the release of a badly
      needed new apothecary bill until 1906. The introduction of a specific
      pharmaceutical curriculum at the university in 1853 was a great step forward to
      improve the pharmaceutical education. Nevertheless, the secondary school exam was
      not compulsory for the studies until 1920 and, therefore, the graduates were not
      on a par with other university graduates before that date. Women, except nuns,
      were not allowed to work as pharmacists until 1900.

PMID- 21179354
TI  - Method development and validation of montelukast in human plasma by HPLC coupled
      with ESI-MS/MS: application to a bioequivalence study.
AB  - A simple, sensitive, and specific LC-ESIaMS/MS method for quantification of
      Montelukast (MO) in human plasma using Montelukast-d(6) (MOD6) as an internal
      standard (IS) is discussed here. Chromatographic separation was performed on YMC
      pack pro C(18), 50 x 4.6 mm, S-3 Im column with an isocratic mobile phase
      composed of 10mM ammonium formate (pH 4.0):acetonitrile (20:80 v/v), at a flow
      rate of 0.8 mL min(a1). MO and MOD6 were detected with proton adducts at m/z
      586.2a568.2 and 592.3a574.2 in multiple reaction monitoring (MRM) positive mode
      respectively. MO and MOD6 were extracted using acetonitrile as precipitating
      agent. The method was validated over a linear concentration range of 1.0a800.0 ng
      mL(a1) with correlation coefficient (r(2)) a 0.9996. The intraday precision and
      accuracy were within 1.91a7.10 and 98.32a99.17. The inter-day precision and
      accuracy were within 3.42a4.41% and 98.14a99.27% for MO. Both analytes were found
      to be stable throughout three freeze-thawing cycles, bench top, and autosampler
      stability studies. This method was utilized successfully for the analysis of
      plasma samples following oral administration of MO (5 mg) in 31 healthy Indian
      male human volunteers under fasting conditions.

PMID- 21179355
TI  - Production, quality control and pharmacokinetic studies of Ho-EDTMP for
      therapeutic applications.
AB  - (166)Ho-EDTMP is a major therapeutic agent which is widely used in bone
      palliation therapy. In this study, a (166)Ho-EDTMP complex was prepared
      successfully using an in-house synthesized EDTMP ligand and (166)HoCl(3). Ho-166
      chloride was obtained by thermal neutron irradiation (1 A 10(13) ncm(a2)s(a1)) of
      natural Ho(NO(3))(3) samples (specific activity = 3a5 GBq/mg), dissolved in
      acidic media. The radiochemical purity of (166)Ho-EDTMP was checked by ITLC
      (>99%) and stability studies in presence of human serum and final preparation
      were performed. The biodistribution of (166)Ho-EDTMP and (166)HoCl(3) in wild
      type rats was checked by scarification. SPECT imaging of (166)Ho-EDTMP was also
      performed in wild-type rats. A comparative accumulation study for (166)Ho-EDTMP
      and (166)HoCl(3) was performed for vital organs up to 48h. Significant bone
      accumulation (>70%) of the tracer in 48h was observed.

PMID- 21179356
TI  - Contribution of thromboxane a2 in rat common carotid artery response to
      serotonin.
AB  - Serotonin is a vasoactive substance that in different blood vessels mostly
      induces vasoconstriction. Considering the important role of common carotid artery
      in brain blood supply, the aims of this study were to investigate the effect of
      serotonin on isolated rat common carotid artery and also to examine participation
      of intact endothelium, cyclooxygenase products, Ca(++) channels and 5-HT(2)
      receptors in serotonin-evoked action. Endothelium was mechanically removed from
      some vascular rings. Circular artery segments were placed in organ baths
      containing KrebsaRinger bicarbonate solution. Cumulative concentration
      contraction curves for serotonin were obtained in rings previously equilibrated
      at basal tone. Serotonin produced concentration-dependent contraction, which was
      unaltered by endothelial denudation. Serotonin-induced effect was notably and
      comparably reduced by indomethacin (cyclooxygenase inhibitor) or OKYa046
      (thromboxane A(2)-synthase inhibitor) on intact or denuded rings. Nifedipine
      (Ca(++) channel blocker) or ketanserin (5-HT(2) receptor antagonist) strongly
      reduced serotonin-evoked effect. Our results suggest that serotonin produced
      concentration-dependent and endothelium-independent contraction of carotid
      artery, which was initiated by activation of 5-HT(2) receptors located on smooth
      muscle cells and mediated via L-type Ca(++) channels. Thromboxane A(2) from
      smooth muscle cells notably contributed to the overall contraction of carotid
      artery induced by serotonin.

PMID- 21179357
TI  - Absorption, distribution and excretion of 14C-probimane in mice bearing lewis
      lung carcinoma.
AB  - Spontaneous neoplasm metastasis, a fatalist pathological feature of cancer, is a
      long-evolving, multi-steps process that can now only be treated or controlled by
      drugs or immuno-modulators. Probimane (Pro), as a representative of the well
      known class of antimetastatic agents aBisdioxopiperazine compounds (Biz)a, is
      systematically studied for its absorption, distribution and excretion in mice
      bearing Lewis lung carcinoma by a radioactivity-detective method in this
      investigation. It is found that the (14)C-Pro concentrations in different normal
      organs of mice at 2 hrs are very high and dramatically declined at 24 and 48 hrs.
      However, Pro concentrations in metastatic foci are slightly changed at the same
      time. Almost no change of Pro concentrations is observed in pulmonary metastatic
      nodules within 48 hrs. This evidence can be used to explain the characteristics
      of good metastatic inhibition by Biz compounds. The radioactivity in brain is
      relatively low because Pro can hardly penetrate into the blood-brain-barrier to
      eliminate brain tumors. The excretion of (14)C-Pro is observed at the same ratios
      from both urine and feces and also at constant rates. These data are much useful
      for better understanding of the general pharmacological characters and possible
      antimetastatic mechanisms of actions of probimane and other Biz compounds from a
      new perspective and research angles.

PMID- 21179358
TI  - Behavioral and developmental changes in rats with prenatal exposure of
      mirtazapine.
AB  - Mirtazapine is an often used antidepressant drug; however insufficient
      information is available regarding its safety during pregnancy. Therefore, this
      work was initiated to study the effect of prenatal exposure of mirtazapine on
      postnatal developments of rats. The study was conducted on pregnant rats to
      observe the safety profile of mirtazapine in comparison to control. The
      percentage weight gain, gestation period and litter size of the rats treated with
      double therapeutic dose (DTD) was significantly lower than the rats treated with
      therapeutic dose (TD) and rats of control group. However the litter size of the
      TD treated rats was also found smaller than the control. The offspring were
      examined through battery of test in order to evaluate their developmental
      neurotoxicity. The test includes the assessment of postnatal growth, reflex
      ontogeny, neuromotor abilities, activity level, emotional reactivity and learning
      ability. The DTD exposure negatively affected on overall growth of pups in
      comparison to TD exposed pups and control group. Further, the amine concentration
      in brain was also found significantly lower in DTD exposed pups. Therefore, this
      study reveals that the treatment of pregnant rats with TD and DTD decreases their
      litter size. In addition the prenatal exposure of DTD of mirtazapine negatively
      affects on neurodevelopment of rats.

PMID- 21179359
TI  - Effect of itraconazole on the pharmacokinetics of diclofenac in beagle dogs.
AB  - The objective of this study was to investigate the potential effect of
      itraconazole on the pharmacokinetics of diclofenac potassium in beagle dogs after
      oral coadministration. Five male beagle dogs received a single oral 50 mg dose of
      diclofenac potassium alone in phase I, and along with a single oral 100 mg dose
      of itraconazole in phase II. Blood samples obtained for 8.0 hours post dose were
      analysed for diclofenac concentration using a validated high performance liquid
      chromatography (HPLC) assay method. The area under plasma concentration-time
      curve (AUC(0aa)), maximum plasma concentration (C(max)), time to reach C(max)
      (T(max)) and elimination half-life (t(1/2)), were calculated for diclofenac
      before and after itraconazole administration. The coadministration of
      itraconazole with diclofenac potassium has resulted in a significant reduction in
      AUC(0aa) and C(max) of diclofenac, which was about 31 and 42%; respectively. No
      statistically significant differences were observed for T(max) and t(1/2) of
      diclofenac between the two phases. Therefore, it could be concluded that oral
      coadministration of itraconazole may have the potential to affect the absorption
      of diclofenac as indicated by the significant reduction in its AUC and C(max) in
      beagle dogs.

PMID- 21179360
TI  - Investigation of the volatile fraction of rosemary infusion extracts.
AB  - The relative proportions of chemical classes (hydrocarbons, oxides, alcohols,
      ketones, esters) in the essential oil of rosemary (Rosmarinus officinalis L.,
      Lamicaeae) and in the volatile fraction of the infusion extracts were examined
      and showed remarkable differences.The volatile compounds of the infusion were
      isolated by two different methods, hydrodistillation and solid phase extraction
      (SPE). The main constituents of the volatile fraction of the infusion were
      (hydrodistillation/SPE): 1,8-cineole (42.4%/44.7%), camphor (31.4%/31.8%), I
      terpineol (8.6%/8.1%) and borneol (8.3%/7.8%). The qualitative and quantitative
      composition of the volatile compounds of the infusion was compared to the
      essential oil isolated by hydrodistillation directly from the leaves. The major
      constituents of the essential oil of the leaves were 1,8-cineole (41.6%), camphor
      (17.0%), I-pinene (9.9%), I-terpineol (4.9%) and borneol (4.8%). Comparison of
      the total essential oil yield quantified by hydrodistillation of the infusion
      (0.36% v/w) with the essential oil yield of the leaves (1.84% v/w) revealed that
      only 19.6% of the initial oil could be extracted by infusion.

PMID- 21179361
TI  - Assessment of insulin stability inside diblock copolymer PEG-PLA microspheres.
AB  - Insulin-loaded PEG2-PLA40 and PEG5-PLA20 microspheres containing 5% bovine
      insulin were manufactured using single emulsion and w/o/w multiple emulsion
      solvent evaporation techniques. Microspheres were characterized for their insulin
      encapsulation efficiency and release characteristics in phosphate-buffered saline
      (PBS) at pH 7.4 and 37 AC. Moreover, the stability of the peptide during 18 days
      of release was evaluated using HPLC and HPLC-MS techniques. The results showed
      that the loading efficiencies were higher in case of insulin loaded PEG2-PLA40
      and PEG5-PLA20 microspheres prepared by single emulsion emulsion-solvent
      evaporation technique. Insulin release was characterized by an initial burst,
      which was attributed to the amount of protein located on or close to the
      microsphere surface. The total ion chromatogram (TIC) of insulin samples
      extracted after 6, 12 and 18 days of PEG2-PLA40 microspheres erosion showed that
      insulin was intact inside the eroding microspheres. In addition, only small
      amounts of protein undergo degradation under these conditions (only 11.69% A 1.13
      of the initially loaded insulin loading were detected as degradation products
      after 18 days. Mass spectra recorded at these retention times confirmed the
      presence of insulin with a molar mass of 5734 Da and other two products of molar
      masses of 5587 Da and 5487 Da.

PMID- 21179362
TI  - Tamoxifen citrate encapsulated sustained release liposomes: preparation and
      evaluation of physicochemical properties.
AB  - The present study was designed for the development of a stable sustained release
      liposomal drug delivery system for tamoxifen citrate (TC) using soya
      phosphatidylcholine (SPC), cholesterol (CH) and span 20 as main ingredients.
      Liposomes were prepared by formation of thin lipid film followed by hydration.
      The mean vesicle diameter was found to be 203.5 A 19.5 nm with 21% of the
      liposomal population having average diameter below 76.72 A 6.7 nm. There was a
      good vesicular distribution with the polydispersity index of 0.442 A 0.03. The
      maximum loading of drug was determined to be 53.60% of the initial amount that is
      34.58 Ig of drug per mg of lipid. Amongst the different storage conditions,
      liposomes stored at 2a8AC were found to be most stable and only 4% of the drug
      was lost over the storage period of 5 weeks. In vitro release studies of
      liposomes showed that 50% of drug was released within 3 hours (h) whereas 95%
      drug was released in 30 h. This indicates the usefulness of the liposomal
      delivery system for sustaining the in vitro release of tamoxifen citrate.

PMID- 21179366
TI  - Studies on the reactivity of (9-Methyl-5,6-dihydronaphtho[1a,2a:4,5]-thieno[2,3
      d]pyrimidin-11-yl)hydrazine towards some reagents for biological evaluation.
AB  - (9-Methyl-5,6-dihydronaphtho[1a,2a:4,5]thieno[2,3-d]pyrimidin-11-yl)hydrazine (1)
      was used as a precursor for preparation of some novel 1-(9-methyl-5,6
      dihydronaphtho[1a,2a:4,5]thieno[2,3-d]pyrimidin-11-yl)-1H-pyrazoles 2a7, -1H
      isoindole-1,3(2H)-dione 8, and -pyridazin-3(2H)-one 9. Moreover, the acyclic C
      nucleosides 10 and 11 were prepared by treating compound 1 with D-glucose. The in
      vitro antimicrobial activity of the tested compounds was evaluated by measuring
      the zone diameters and some of the prepared products showed potent antimicrobial
      activity in compared with those of well known drugs (standard). In general, the
      non-acetylated sugar hydrazone derivative 10 showed the highest antibacterial and
      antifungal potency among the tested compounds and standard with IZ = 22, 21 and
      22 mm and MIC = 62.5 and 31.25 Ig/ml, respectively.

PMID- 21179367
TI  - Different spontaneous pulmonary metastasis inhibitions against lewis lung
      carcinoma in mice by bisdioxopiperazine compounds of different treatment
      schedules.
AB  - Spontaneous neoplasm metastasis, a fatalist pathological feature of cancer, is a
      long-evolving, multi-steps process that can now only be treated or controlled by
      drugs or immuno-modulators. As we have previously hypothesized, each drug or
      immuno-modulator might act differently within various stages of a metastasis.
      Therefore any researches helping to determine these differences will be
      beneficial for updating therapeutics for metastasis. In this work, we have
      testified this hypothesis by using a series of well-known anti-metastatic agents
      a Bisdioxopiperazine compounds.

PMID- 21179368
TI  - Antioxidant and immunomodulatory activity of the alkaloidal fraction of
      Cissampelos pareira linn.
AB  - The alkaloidal fraction (AFCP) of roots of Cissampelos pareira Linn. was screened
      for in-vitro antioxidant activity and immunomodulatory activity in mice. The
      HPTLC finger print profile was also established for the identification of AFCP
      which was found to contain 0.176 % of berberine. AFCP possess strong antioxidant
      activity which was revealed by its ability to scavenge the stable free radical
      DPPH, superoxide ion and to inhibit lipid peroxidation in rat liver homogenate
      induced by iron/ADP/Ascorbate complex. AFCP was found to have significant
      immunosuppressive activity at lower doses (25 and 50 mg/kg) while no activity was
      observed at higher doses (75 and 100 mg/kg). Humoral antibody titre was
      significantly (p<0.01) lowered by AFCP at the doses of 25 and 50 mg/kg. Delayed
      type hypersensitivity response was also significantly (p<0.01) suppressed by the
      AFCP at the dose of 75 mg/kg. Thus the present study revealed the
      immunosuppressive and antioxidant activities of the alkaloidal fraction of C.
      pareira roots.

PMID- 21179369
TI  - Preparation and in vivo evaluation of indomethacin loaded true nanoemulsions.
AB  - Indomethacin, a potent nonsteroidal anti-inflammatory drug, has been used in the
      treatment of various kinds of pains, inflammation and arthritis. However, oral
      administration of indomethacin produces serious gastrointestinal adverse effects.
      Therefore the aim of the present investigation was to evaluate the anti
      inflammatory effects, skin irritation, activation energy and histopathology of
      indomethacin from transdermally applied true nanoemulsion. The anti-inflammatory
      effects of true nanoemulsions were compared with marketed Indobene(A) gel on
      carrageenan-induced paw edema in rats. Skin irritation tests were performed on
      Wistar rats for 14 days. The % inhibition value after 12 h application was
      significant for optimized formulation F6 (83) as compared to marketed Indobene(A)
      gel (P<0.01). Results of skin irritation test indicated that developed true
      nanoemulsion is safe for human use. The significant decrease in activation energy
      (1.396 kcal/mol) for indomethacin across rat skin indicated that the stratum
      corneum lipid bilayers were significantly disrupted (P<0.05). From these results
      it was concluded that the developed nanoemulsion have great potential for
      transdermal application of indomethacin.

PMID- 21179370
TI  - Chitosan-carboxymethyl tamarind kernel powder interpolymer complexation:
      investigations for colon drug delivery.
AB  - The present study was aimed at evaluating the possible use of inter polymer
      complexed (IPC) films of chitosan (CH) and carboxymethyl tamarind kernel powder
      (CMTKP) for colon release of budesonide. Viscosity analysis of the supernatant
      liquid obtained after reacting CH and CMTKP in different proportions revealed
      40:60 to be the optimum stoichiometric ratio. The FTIR spectra of IPC films
      formed from 50:50 or 40:60 ratio of CH:CMTKP did not reveal any reduction in the
      peaks at 1560cm(a1) and 1407cm(a1) after exposure to pH 1.2, suggesting
      resistance of the interaction between aCOO(a) groups of CMTKP and aNH(3) (+)
      groups of CH to gastric pH. Tablets containing Avicel pH 102 as diluent and
      coated to a weight gain of 10%, w/w with aqueous solutions of 40:60 or 50:50
      ratio of CH:CMTKP did not release budesonide in pH 1.2 buffer. Histopathology of
      the rat colon after oral administration of these IPC film coated tablets revealed
      significantly greater (p<0.05) reduction in TNBS-induced ulcerative colitis as
      compared to that after administration of uncoated tablets. The Cmax of budesonide
      achieved after oral administration of these IPC film coated tablets was
      comparable to that observed after administration of uncoated tablets. The results
      strongly indicate versatility of CH-CMTKP IPC films to deliver budesonide in the
      colon.

PMID- 21179371
TI  - Evaluation of ketorolac tromethamine microspheres by chitosan/gelatin B complex
      coacervation.
AB  - Microspheres (MS) of Ketorolac Tromethamine (KT) for oral delivery were prepared
      by complex coacervation (method-1) and simple coacervation (method-2) methods
      without the use of chemical crossalinking agent (glutaraldehyde) to avoid the
      toxic reactions and other undesirable effects of the chemical cross-linking
      agents. Alternatively, ionotropic gelation was employed by using sodium
      tripolyphosphate (Na-TPP) as cross linking agent. Chitosan and gelatin B were
      used as polymer and copolymer respectively. All the prepared microspheres were
      subjected to various physico-chemical studies, such as drug-polymer compatibility
      by Thin Layer Chromatography (TLC) and Fourier Transform Infra Red Spectroscopy
      (FTIR), surface morphology by Scanning Electron Microscopy (SEM), frequency
      distribution, encapsulation efficiency, in-vitro drug release characteristics and
      release kinetics. The physical state of drug in the microspheres was determined
      by Differential Scanning Calorimetry (DSC) and X-ray powder Diffractometry (XRD).
      TLC and FTIR studies indicated no drug-polymer incompatibility. All the MS showed
      release of drug by a fickian diffusion mechanism. DSC and XRD analysis indicated
      that the KT trapped in the microspheres existed in an amorphous or disordered
      crystalline status in the polymer matrix. It is possible to design a controlled
      drug delivery system for the prolonged release of KT, improving therapy by
      possible reduction of time intervals between administrations.

PMID- 21179372
TI  - Release kinetic studies of aspirin microcapsules from ethyl cellulose, cellulose
      acetate phthalate and their mixtures by emulsion solvent evaporation method.
AB  - The present study was oriented towards microencapsulation of aspirin and the
      study of its release kinetics. The desired encapsulation was achieved by emulsion
      solvent evaporation method using ethyl cellulose (EC), cellulose acetate
      phthalate (CAP) and their mixture (1:1) of polymeric constituents.
      Characterization of the formulations was performed by size, shape, drug loading
      efficiency and in-vitro drug release analysis. The in-vitro release profiles from
      different polymeric microcapsules were applied on different kinetic models. The
      prepared microcapsules were found free flowing and almost spherical in shape with
      particle sizes ranging from 300a700Im, having a loading efficiency of 75a85%. The
      best fit model with the highest correlation coefficient was observed in Higuchi
      model, indicating diffusion controlled principle. The n value obtained from
      Korsemeyer-Peppas model varied between 0.5a0.7, confirming that the mechanism of
      drug release was diffusion controlled. Comparative studies revealed that the
      release of aspirin from EC microcapsules was slower as compared to that of CAP
      and their binary mixture.

PMID- 21179373
TI  - Antiproliferative activity of plant extracts used against cancer in traditional
      medicine.
AB  - Forty four extracts from sixteen plants used traditionally as anticancer agents
      were evaluated in vitro for their antiproliferative activity against Hep-2, MCF
      7, and Vero cell lines. Plants were fractionated using ethanol, methanol,
      chloroform, n-hexane, distilled water, and butanol. The antiproliferative
      activity was measured by MTT assay. TLC was used to identify active fractions.
      The apoptotic activity of active fractions was determined using TUNEL
      colorimetric assay. 20 of these extracts demonstrated significant
      antiproliferative activity against one or more of the cell lines. These extracts
      were prepared from Ononis hirta, Inula viscosa, Salvia pinardi, Verbascum
      sinaiticum and Ononis sicula. Methanol fractions of Ononis hirta (aerial parts)
      and Inula viscosa (flowers) were the most active fractions against MCF-7 cells
      with IC(50) of 27.96 and 15.78 Ig/ml respectively and they were less toxic
      against other cell lines. Other extracts showed lower activity against cancer
      cell lines. TLC analysis showed the presence of flavonoids and terpenoids in
      active plants while alkaloids were detected in Ononis hirta (aerial parts)
      extracts. Ononis hirta (aerial parts) and Inula viscosa (flowers) extracts
      exerted their antiproliferative activity by inducing apoptosis in cancer cell
      lines. Further studies are necessary for detailed chemical characterization and
      more extensive biological evaluation of the most active ingredients.

PMID- 21179374
TI  - In vivo bioavailability and therapeutic assessment of host-guest inclusion
      phenomena for the hydrophobic molecule etodolac: pharmacodynamic and
      pharmacokinetic evaluation.
AB  - The aim of present investigation was 1) to evaluate the in vivo bioavailability
      of an Etodolac (ETD)-I-cyclodextrin (I-CD) inclusion complex system prepared by
      kneading and spray drying techniques in rats, 2) to study the pharmacodynamic
      parameters in various animal models for analyzing the therapeutic response and,
      3) to evaluate the pharmacokinetic profile of the drug administered. Inclusion
      complexation with I-CD enhanced the solubility of the drug, improved
      bioavailability and reduced ulcerogenicity of ETD in rats. Pharmacodynamic
      studies were carried out in normal LACA mice and pharmacokinetic evaluation was
      done in male Wistar rats. Pharmacokinetic parameters evaluated for the inclusion
      complexes revealed good correlation. The minimum dose necessary to produce
      analgesic or anti-arthritic activity was also decreased, indicating that the host
      guest strategy that uses I-CD and ETD was very effective and could be
      successfully employed in the preparation of pharmaceutical formulations of anti
      arthritics and analgesics.

PMID- 21179375
TI  - Retraction.

PMID- 21179376
TI  - Centennial- to decadal scale environmental shifts in and around Lake Pannon
      (Vienna Basin) related to a major Late Miocene lake level rise.
AB  - A detailed ultra-high-resolution analysis of a 37-cm-long core of Upper Miocene
      lake sediments of the long-lived Lake Pannon has been performed. Despite a
      general stable climate at c. 11-9 Ma, several high-frequency oscillations of the
      paleoenvironments and depositional environments are revealed by the analysis over
      a short time span of less than 1000 years. Shifts of the lake level, associated
      with one major 3rd order flooding are reflected by all organisms by a cascade of
      environmental changes on a decadal scale. Within a few decades, the pollen record
      documents shifting vegetation zones due to the landward migration of the coast;
      the dinoflagellate assemblages switch towards "offshore-type" due to the
      increasing distance to the shore; the benthos is affected by low oxygen
      conditions due to the deepening. This general trend is interrupted by smaller
      scale cycles, which lack this tight interconnection. Especially, the pollen data
      document a clear cyclicity that is expressed by iterative low pollen
      concentration events. These "negative" cycles are partly reflected by
      dinoflagellate blooms suggesting a common trigger-mechanism and a connection
      between terrestrial environments and surface waters of Lake Pannon. The benthic
      fauna of the core, however, does not reflect these surface water cycles. This
      forcing mechanism is not understood yet but periodic climatic fluctuations are
      favoured as hypothesis instead of further lake level changes. Short phases of low
      precipitation, reducing pollen production and suppressing effective transport by
      local streams, might be a plausible mechanism. This study is the first hint
      towards solar activity related high-frequency climate changes during the
      Vallesian (Late Miocene) around Lake Pannon and should encourage further ultra
      high-resolution analyses in the area.

PMID- 21179377
TI  - Similarity-Based Searching in Multi-Parameter Time Series Databases.
AB  - We present a similarity-based searching and pattern matching algorithm that
      identifies time series data with similar temporal dynamics in large-scale, multi
      parameter databases. We represent time series segments by feature vectors that
      reflect the dynamical patterns of single and multi-dimensional physiological time
      series. Features include regression slopes at varying time scales, maximum
      transient changes, auto-correlation coefficients of individual signals, and cross
      correlations among multiple signals. We model the dynamical patterns with a
      Gaussian mixture model (GMM) learned with the Expectation Maximization algorithm,
      and compute similarity between segments as Mahalanobis distances. We evaluate the
      use of our algorithm in three applications: search-by-example based data
      retrieval, event classification, and forecasting, using synthetic and real
      physiologic time series from a variety of sources.

PMID- 21179379
TI  - Pensions and Retirement Among Black Union Army Veterans.
AB  - I examine the effects of an unearned income transfer on the retirement rates and
      living arrangements of black Union Army veterans. I find that blacks were more
      than twice as responsive as whites to income transfers in their retirement
      decisions and 6 to 8 times as responsive in their choice of independent living
      arrangements. My findings have implications for understanding racial differences
      in rates of retirement and independent living at the beginning of the twentieth
      century, the rise in retirement prior to 1930, and the subsequent convergence in
      black-white retirement rates and living arrangements.

PMID- 21179378
TI  - Burn trauma in skeletal muscle results in oxidative stress as assessed by in vivo
      electron paramagnetic resonance.
AB  - Using a mouse model, we tested the hypotheses that severe burn trauma causes
      metabolic disturbances in skeletal muscle, and that these can be measured and
      repeatedly followed by in vivo electron paramagnetic resonance (EPR). We used a
      1.2-GHz (L-band) EPR spectrometer to measure partial pressure of oxygen (pO(2))
      levels, redox status and oxidative stress following a non-lethal burn trauma
      model to the left hind limbs of mice. Results obtained in the burned mouse
      gastrocnemius muscle indicated a significant decrease in tissue pO(2) immediately
      (P=0.032) and at 6 h post burn (P=0.004), compared to the gastrocnemius of the
      unburned hind limb. The redox status of the skeletal muscle also peaked at 6 h
      post burn (P=0.027) in burned mice. In addition, there was an increase in the EPR
      signal of the nitroxide produced by oxidation of the hydroxylamine (CP-H) probe
      at 12 h post burn injury, indicating a burn-induced increase in mitochondrial
      reactive oxygen species (ROS). The nitroxide signal continued to increase between
      12 and 24 h, suggesting a further increase in ROS generation post burn. These
      results confirm genomic results, which indicate a downregulation of antioxidant
      genes and therefore strongly suggest the dysfunction of the mitochondrial
      oxidative system. We believe that the direct measurement of tissue parameters
      such as pO(2), redox and ROS by EPR may be used to complement measurements by
      nuclear magnetic resonance (NMR) in order to assess tissue damage and the
      therapeutic effectiveness of antioxidant agents in severe burn trauma.

PMID- 21179380
TI  - 3D Multi-spectral Image-guided Near-infrared Spectroscopy using Boundary Element
      Method.
AB  - Image guided (IG) Near-Infrared spectroscopy (NIRS) has the ability to provide
      high-resolution metabolic and vascular characterization of tissue, with clinical
      applications in diagnosis of breast cancer. This method is specific to
      multimodality imaging where tissue boundaries obtained from alternate modalities
      such as MRI/CT, are used for NIRS recovery. IG-NIRS is severely limited in 3D by
      challenges such as volumetric meshing of arbitrary anatomical shapes and
      computational burden encountered by existing models which use finite element
      method (FEM). We present an efficient and feasible alternative to FEM using
      boundary element method (BEM). The main advantage is the use of surface
      discretization which is reliable and more easily generated than volume grids in
      3D and enables automation for large number of clinical data-sets. The BEM has
      been implemented for the diffusion equation to model light propagation in tissue.
      Image reconstruction based on BEM has been tested in a multi-threading
      environment using four processors which provides 60% improvement in computational
      time compared to a single processor. Spectral priors have been implemented in
      this framework and applied to a three-region problem with mean error of 6% in
      recovery of NIRS parameters.

PMID- 21179381
TI  - Vascular Health and Cognitive Function in Older Adults with Cardiovascular
      Disease.
AB  - BACKGROUND: We hypothesized that changes in vascular flow dynamics resulting from
      age and cardiovascular disease (CVD) would correlate to neurocognitive
      capacities, even in adults screened to exclude dementia and neurological disease.
      We studied endothelial-dependent as well as endothelial-independent brachial
      responses in older adults with CVD to study the associations of vascular
      responses with cognition. Comprehensive neurocognitive testing was used to
      discern which specific cognitive domain(s) correlated to the vascular responses.
      METHODS: Eighty-eight independent, community-dwelling older adults (70.02+7.67
      years) with mild to severe CVD were recruited. Enrollees were thoroughly screened
      to exclude neurological disease and dementia. Flow-mediated (endothelial
      dependent) and nitroglycerin-mediated (endothelial-independent) brachial artery
      responses were assessed using 2-d ultrasound. Cognitive functioning was assessed
      using comprehensive neuropsychological testing. Linear regression analyses were
      used to evaluate the relationships between the endothelial-dependent and
      endothelial-independent vascular flow dynamics and specific domains of
      neurocognitive function. RESULTS: Endothelial-dependent and endothelial
      independent brachial artery responses both correlated with neurocognitive testing
      indices. The strongest independent relationship was between endothelial function
      and measures of attention-executive functioning. CONCLUSIONS: Endothelial
      dependent and endothelial-independent vascular responsiveness correlate with
      neurocognitive performance among older CVD patients, particularly in the
      attention-executive domain. While further study is needed to substantiate causal
      relationships, our data demonstrate that brachial responses serve as important
      markers of risk for common neurocognitive changes. Learning and behavior
      modifying therapeutic strategies that compensate for such common, insidious
      neurocognitive limitations will likely improve caregiving efficacy.

PMID- 21179382
TI  - INTERNATIONAL MIGRATION AND EDUCATION OF LEFT BEHIND CHILDREN IN FUJIAN, CHINA.
AB  - This study examines the educational consequences for those children of emigrants
      who are left behind in Fujian Province, China. Specifically, we compare the
      school enrollment for children from emigrant households with the school
      enrollment for children from non-emigrant households. The data are drawn from the
      1995 China 1% Population Sample Survey. We find consistent evidence that
      emigration affects educational opportunity for children in a positive way. First,
      children from emigrant households are more likely to be enrolled in schools than
      children from non-emigrant households. Second, emigration also has positive
      consequences in reducing gender gap in education. Although girls from non
      emigrant households still experience a lower enrollment rate, for the emigrant
      households the overall school enrollment for boys and girls has been approaching
      convergence.

PMID- 21179383
TI  - EVIDENCE OF SELF-SCHEMATIC COGNITIVE PROCESSING IN WOMEN WITH DIFFERING SEXUAL
      SELF-VIEWS.

PMID- 21179384
TI  - The Role of Emotion Regulation and Children's Early Academic Success.
AB  - This study investigated the role of children's emotion regulation skills and
      academic success in kindergarten, using a sample of 325 five-year-old children. A
      mediational analysis addressed the potential mechanisms through which emotion
      regulation relates to children's early academic success. Results indicated that
      emotion regulation was positively associated with teacher reports of children's
      academic success and productivity in the classroom and standardized early
      literacy and math achievement scores. Contrary to predictions, child behavior
      problems and the quality of the student teacher relationship did not mediate
      these relations. However, emotion regulation and the quality of the student
      teacher relationship uniquely predicted academic outcomes even after accounting
      for IQ. Findings are discussed in terms of how emotion regulation skills
      facilitate children's development of a positive student-teacher relationship and
      cognitive processing and independent learning behavior, both of which are
      important for academic motivation and success.

PMID- 21179386
TI  - A System for Automated Extraction of Metadata from Scanned Documents using Layout
      Recognition and String Pattern Search Models.
AB  - One of the most expensive aspects of archiving digital documents is the manual
      acquisition of context-sensitive metadata useful for the subsequent discovery of,
      and access to, the archived items. For certain types of textual documents, such
      as journal articles, pamphlets, official government records, etc., where the
      metadata is contained within the body of the documents, a cost effective method
      is to identify and extract the metadata in an automated way, applying machine
      learning and string pattern search techniques.At the U. S. National Library of
      Medicine (NLM) we have developed an automated metadata extraction (AME) system
      that employs layout classification and recognition models with a metadata pattern
      search model for a text corpus with structured or semi-structured information. A
      combination of Support Vector Machine and Hidden Markov Model is used to create
      the layout recognition models from a training set of the corpus, following which
      a rule-based metadata search model is used to extract the embedded metadata by
      analyzing the string patterns within and surrounding each field in the recognized
      layouts.In this paper, we describe the design of our AME system, with focus on
      the metadata search model. We present the extraction results for a historic
      collection from the Food and Drug Administration, and outline how the system may
      be adapted for similar collections. Finally, we discuss some ongoing enhancements
      to our AME system.

PMID- 21179385
TI  - Single-molecule fluorescence characterization in native environment.
AB  - Single-molecule detection (SMD) with fluorescence is a widely used microscopic
      technique for biomolecule structure and function characterization. The modern
      light microscope with high numerical aperture objective and sensitive CCD camera
      can image the brightly emitting organic and fluorescent protein tags with
      reasonable time resolution. Single-molecule imaging gives an unambiguous bottom
      up biomolecule characterization that avoids the "missing information" problem
      characteristic of ensemble measurements. It has circumvented the diffraction
      limit by facilitating single-particle localization to ~1 nm. Probes developed
      specifically for SMD applications extend the advantages of single-molecule
      imaging to high probe density regions of cells and tissues. These applications
      perform under conditions resembling the native biomolecule environment and have
      been used to detect both probe position and orientation. Native, high density SMD
      may have added significance if molecular crowding impacts native biomolecule
      behavior as expected inside the cell.

PMID- 21179387
TI  - Prolonged Exposure Therapy and Irritable Bowel Syndrome: A Case Study Examining
      the Impact of a Trauma-Focused Treatment on a Physical Condition.
AB  - Previous research has shown that psychological treatments, particularly those
      employing cognitive techniques, are particularly effective in the treatment of
      irritable bowel syndrome (IBS). It is presumed that these psychological
      interventions are effective at ameliorating the IBS by treating an underlying
      psychological disorder (often an anxiety disorder), which may be contributing to
      the autonomic reactivity. This case study examined the change in the physical
      symptoms of IBS for a patient seeking treatment for rape-related PTSD with
      comorbid conditions of major depression and panic. At posttreatment, the patient
      no longer met criteria for PTSD, major depression, or panic. In addition, her
      primary symptom of IBS, diarrhea frequency, was significantly improved. These
      findings were maintained at 3 and 9 months posttreatment. Implications for the
      assessment and treatment of IBS patients with PTSD are discussed.

PMID- 21179388
TI  - Increased expression and co-localization of ACE, angiotensin II AT(1) receptors
      and inducible nitric oxide synthase in atherosclerotic human coronary arteries.
AB  - Using immunohistochemistry and quantitative in vitro autoradiography, the present
      study was undertaken to examine whether co-expression of pro-atherosclerotic
      factors, ACE, the AT(1) receptor, and iNOS, is increased in early and advanced
      atherosclerotic lesions of human coronary arteries. In normal coronary arteries,
      ACE and eNOS were strongly co-expressed in endothelial cells (ECs), whereas the
      AT(1) receptor was expressed in medial smooth muscle cells (SMCs). By contrast,
      iNOS was not expressed in ECs and SMCs. In early atherosclerotic lesions and
      atheromatous plaques, ACE, the AT(1) receptor and iNOS immunostaining were
      primarily co-localized in infiltrated macrophages and SMCs adjacent to
      macrophages. eNOS expression was lower in ECs than in normal arteries, and absent
      in accumulated macrophages and SMCs. In fibrosclerotic plaques, ACE, the AT(1)
      receptor, and iNOS immunostaining were still positive in macrophages as well as
      new microvessels within the plaques. Interestingly, SMCs in vasa vasorum of the
      adventitia in atheromatous and fibrosclerotic plaques were also strongly positive
      for AT(1) receptor and iNOS, while ECs of the vasa vasorum were positive for ACE
      and eNOS. The present study demonstrates that multiple pro-atherosclerotic
      factors ACE, AT(1) receptor and iNOS are co-localized almost exclusively in
      infiltrated macrophages and SMCs that have accumulated in or adjacent to early
      and advanced atherosclerotic plaques, while the anti-atherosclerotic enzyme eNOS
      is reduced in ECs. These data therefore suggest that increased formation of Ang
      II and iNOS in infiltrated macrophages and medial SMCs might well play important
      roles in the development and progression of human coronary atherosclerosis.

PMID- 21179390
TI  - Role of the BCA2 ubiquitin E3 ligase in hormone responsive breast cancer.
AB  - The BCA2 protein contains a RING H2 finger and a Zn finger near the N-terminus
      and has E3 ligase activity. RING finger proteins play critical roles in mediating
      the transfer of ubiquitin and ubiquitin like modifiers to heterologous substrates
      as well as to the RING finger proteins themselves. Protein modification by
      ubiquitin and small ubiquitin-related modifier (SUMO) plays a pivotal role in
      protein homeostasis and is critical to regulating basic cellular processes such
      as proliferation, differentiation, apoptosis, intracellular signaling, and gene
      transcriptional regulation. The addition of ubiquitin or SUMO can modulate the
      ability of proteins to interact with their partners, alter their patterns of sub
      cellular localization and control their stability. It is clear that SUMO
      influences many different biological processes however recent data suggest that
      it is specifically important in the regulation of transcription. BCA2 is an E3
      ligase that interacts with the SUMO conjugating enzyme Ubc9. It could therefore
      function as an E3 in the sumoylation of various transcription factors. We have
      found that the BCA2 is co-expressed with the estrogen receptor in 74% of ER
      positive invasive ductal carcinomas from a 635 member breast cancer cohort (p =
      0.004). At the cellular level, BCA2 co-localizes with ER and it appears that at
      the transcriptional level BCA2 mRNA expression is regulated by estrogen.
      Bioinformatic analysis of the BCA2 promoter region revealed ER and PR binding
      sites as well as that of other more general transcription factors. The data
      presented here provides an overview of the potential involvement of the BCA2 in
      hormone responsive breast cancer and opens up avenues that should be exploited to
      better understand the regulation of ER expression, growth of breast cancer cells,
      and the importance of BCA2.

PMID- 21179391
TI  - An RFID-Based Closed-Loop Wireless Power Transmission System for Biomedical
      Applications.
AB  - This brief presents a standalone closed-loop wireless power transmission system
      that is built around a commercial off-the-shelf (COTS) radio-frequency
      identification (RFID) reader (TRF7960) operating at 13.56 MHz. It can be used for
      inductively powering implantable biomedical devices in a closed loop. Any changes
      in the distance and misalignment between transmitter and receiver coils in near
      field wireless power transmission can cause a significant change in the received
      power, which can cause either a malfunction or excessive heat dissipation. RFID
      circuits are often used in an open loop. However, their back telemetry capability
      can be utilized to stabilize the received voltage on the implant. Our
      measurements showed that the delivered power to the transponder was maintained at
      11.2 mW over a range of 0.5 to 2 cm, while the transmitter power consumption
      changed from 78 mW to 1.1 W. The closed-loop system can also oppose voltage
      variations as a result of sudden changes in the load current.

PMID- 21179392
TI  - A simple regularizer for B-spline nonrigid image registration that encourages
      local invertibility.
AB  - Nonrigid image registration is an important task for many medical imaging
      applications. In particular, for radiation oncology it is desirable to track
      respiratory motion for thoracic cancer treatment. B-splines are convenient for
      modeling nonrigid deformations, but ensuring invertibility can be a challenge.
      This paper describes sufficient conditions for local invertibility of
      deformations based on B-spline bases. These sufficient conditions can be used
      with constrained optimization to enforce local invertibility. We also incorporate
      these conditions into nonrigid image registration methods based on a simple
      penalty approach that encourages diffeomorphic deformations. Traditional Jacobian
      penalty methods penalize negative Jacobian determinant values only at grid
      points. In contrast, our new method enforces a sufficient condition for
      invertibility directly on the deformation coefficients to encourage invertibility
      globally over a 3D continuous domain. The proposed penalty approach requires
      substantially less compute time than Jacobian penalties per iteration.

PMID- 21179394
TI  - BAYESIAN MODEL SEARCH AND MULTILEVEL INFERENCE FOR SNP ASSOCIATION STUDIES.
AB  - Technological advances in genotyping have given rise to hypothesis-based
      association studies of increasing scope. As a result, the scientific hypotheses
      addressed by these studies have become more complex and more difficult to address
      using existing analytic methodologies. Obstacles to analysis include inference in
      the face of multiple comparisons, complications arising from correlations among
      the SNPs (single nucleotide polymorphisms), choice of their genetic
      parametrization and missing data. In this paper we present an efficient Bayesian
      model search strategy that searches over the space of genetic markers and their
      genetic parametrization. The resulting method for Multilevel Inference of SNP
      Associations, MISA, allows computation of multilevel posterior probabilities and
      Bayes factors at the global, gene and SNP level, with the prior distribution on
      SNP inclusion in the model providing an intrinsic multiplicity correction. We use
      simulated data sets to characterize MISA's statistical power, and show that MISA
      has higher power to detect association than standard procedures. Using data from
      the North Carolina Ovarian Cancer Study (NCOCS), MISA identifies variants that
      were not identified by standard methods and have been externally "validated" in
      independent studies. We examine sensitivity of the NCOCS results to prior choice
      and method for imputing missing data. MISA is available in an R package on CRAN.

PMID- 21179393
TI  - Translocation events in a single walled carbon nanotube.
AB  - Translocation of DNA oligomers through a single walled carbon nanotube was
      demonstrated recently. Translocation events are accompanied by giant current
      pulses, the origin of which remains obscure. Here, we show that introduction of a
      nucleotide alone, guanosine triphosphate into the input reservoir of a carbon
      nanotube nanofluidic also gives giant current pulses. Taken together with data on
      oligomer translocation, theses new results suggest that pulse width has a non
      linear, power-law dependence on the number of nucleotides in a DNA molecule. We
      have also measured the time for the onset of DNA translocation pulses after bias
      reversal, finding that the time for the onset of translocation is directly
      proportional to the period of bias reversal.

PMID- 21179395
TI  - Nanotexture Optimization by Oxygen Plasma of Mesoporous Silica Thin Film for
      Enrichment of Low Molecular Weight Peptides Captured from Human Serum.
AB  - This study investigated the optimization of mesoporous silica thin films by
      nanotexturing using oxygen plasma versus thermal oxidation. Calcination in oxygen
      plasma provides superior control over pore formation with regard to the pore
      surface and higher fidelity to the structure of the polymer template. The
      resulting porous film offers an ideal substrate for the selective partitioning of
      peptides from complex mixtures. The improved chemico-physical characteristics of
      porous thin films (pore size distribution, nanostructure, surface properties and
      pore connectivity) were systematically characterized with XRD, Ellipsometry,
      FTIR, TEM and N(2) adsorption/desorption. The enrichment of low molecular weight
      proteins captured from human serum on mesoporous silica thin films fabricated by
      both methodologies were investigated by comparison of their MALDI-TOF MS
      profiles. This novel on-chip fractionation technology offers advantages in
      recovering the low molecular weight peptides from human serum, which has been
      recognized as an informative resource for early diagnosis of cancer and other
      diseases.

PMID- 21179396
TI  - Systems of Care and the Prevention of Mental Health Problems for Children and
      their Families: Integrating Counseling Psychology and Public Health Perspectives.
AB  - The purpose of this paper is to present systems of care as an example of how
      counseling psychology and public health overlap with regards to prevention and
      intervention approaches for children's mental health. A framework for prevention
      is presented as is the state of children's mental health promotion, with a
      particular focus on ecological and systemic approaches to children's mental
      health and how these approaches cut across multiple perspectives. Systems of care
      are highlighted as an example of the congruence of prevention and ecological or
      systemic approaches to address the mental health promotion of children and their
      families, with the potential to impact at the universal, selective, and indicated
      levels of risk. Results from a longitudinal outcome study of a school-based
      system of care are presented to exemplify the positive outcomes experienced by
      children. An increase in the awareness and implementation of systems of care
      across mental health perspectives is recommended, along with continued research
      from the public health and counseling psychology communities focused on which
      prevention and intervention services within systems of care work, why they work,
      and how they can be improved upon.

PMID- 21179397
TI  - Fine Mapping of a Deafness Mutation hml on Mouse Chromosome 10.
AB  - OBJECTIVE: to map a mouse deafness gene, identify the underlying mutation and
      develop a mouse model for human deafness. METHODS: genetic linkage cross and
      genome scan were used to map a novel mutation named hypoplasia of the membranous
      labyrinth (hml), which causes hearing loss in mutant mice. RESULTS: 1. hml was
      mapped on mouse Chr 10 (~43 cM from the centromere) suggests that the homologous
      human gene is on 12q22-q24, which was defined on the basis of known mouse-human
      homologies (OMIM, 2004). 2. This study has generated 25 polymorphic
      microsatellite markers, placed 3 known human genes in the correct order in a high
      resolution mouse map and narrowed the hml candidate gene region to a 500kb area.

PMID- 21179398
TI  - PI3Kalpha inhibitors that inhibit metastasis.
AB  - Previous genetic analyses have suggested that mutations of the genes encoding
      PI3Kalpha facilitate invasion and metastasis but have less effect on primary
      tumor growth. These findings have major implications for therapeutics but have
      not been factored into pre-clinical drug development designs. Here we show that
      the inhibition of PI3Kalpha by newly designed small molecule inhibitors prevented
      metastasis formation in mice but had much less effect on the growth of
      subcutaneous xenografts or primary intra-abdominal tumors. These data support the
      idea that PI3Kalpha plays an important role in the metastatic process and suggest
      a more informed strategy for selecting drugs worthy of further development for
      clinical application.

PMID- 21179400
TI  - Neuron, Glia and Reciprocal Relationships in Pain Processing.

PMID- 21179399
TI  - Localized Intervertebral Disc Injury Leads to Organ Level Changes in Structure,
      Cellularity, and Biosynthesis.
AB  - A literature review and new data are presented to evaluate the influence of
      intervertebral disc (IVD) injury on biomechanics, cellularity, inflammation, and
      biosynthesis. Literature and new experimental evidence support the hypothesis
      that localized injury in the disc can lead to immediate and long-term organ level
      changes in biomechanics and biology of the IVD. Biomechanical properties defining
      motion segment bending behaviors sensitive to injuries that affect anulus
      fibrosus (AF) integrity and nucleus pulposus (NP) pressurization. Axial mechanics
      and IVD height measurements show sensitivity to puncture and other injuries that
      reduce NP pressurization. Torsional biomechanics are strongly affected by the
      extent and location of AF lesions but are less sensitive to reduced NP
      pressurization. IVD injuries such as puncture and stab incisions may also lead to
      a cascade of biological changes consistent with degeneration, including loss of
      cellularity, altered biosynthesis and inflammation. New results on effects of 25G
      needle injection of saline into a bovine IVD organ culture model demonstrated a
      loss of cellularity and down-regulation of matrix gene expression, providing a
      specific example of how a minor injury affects the IVD organ response. We
      conclude that localized injuries in the IVD can induce an organ level
      degenerative cascade through biomechanical and biological mechanisms, and their
      interactions. Attempts at IVD repair should target the dual biomechanical roles
      of the anulus of maintaining nucleus pressurization and transmitting loads across
      the vertebrae. Biologically, it remains important to maintain IVD cellularity and
      biosynthesis rates following injury to prevent downstream degenerative changes.

PMID- 21179401
TI  - Feedback Control for Steering Needles Through 3D Deformable Tissue Using Helical
      Paths.
AB  - Bevel-tip steerable needles are a promising new technology for improving accuracy
      and accessibility in minimally invasive medical procedures. As yet, 3D needle
      steering has not been demonstrated in the presence of tissue deformation and
      uncertainty, despite the application of progressively more sophisticated planning
      algorithms. This paper presents a feedback controller that steers a needle along
      3D helical paths, and varies the helix radius to correct for perturbations. It
      achieves high accuracy for targets sufficiently far from the needle insertion
      point; this is counterintuitive because the system is highly under-actuated and
      not locally controllable. The controller uses a model predictive control
      framework that chooses a needle twist rate such that the predicted helical
      trajectory minimizes the distance to the target. Fast branch and bound techniques
      enable execution at kilohertz rates on a 2GHz PC. We evaluate the controller
      under a variety of simulated perturbations, including imaging noise, needle
      deflections, and curvature estimation errors. We also test the controller in a 3D
      finite element simulator that incorporates deformation in the tissue as well as
      the needle. In deformable tissue examples, the controller reduced targeting error
      by up to 88% compared to open-loop execution.

PMID- 21179402
TI  - The social context of cannibalism in migratory bands of the Mormon cricket.
AB  - Cannibalism has been shown to be important to the collective motion of mass
      migratory bands of insects, such as locusts and Mormon crickets. These mobile
      groups consist of millions of individuals and are highly destructive to
      vegetation. Individuals move in response to attacks from approaching conspecifics
      and bite those ahead, resulting in further movement and encounters with others.
      Despite the importance of cannibalism, the way in which individuals make attack
      decisions and how the social context affects these cannibalistic interactions is
      unknown. This can be understood by examining the decisions made by individuals in
      response to others. We performed a field investigation which shows that adult
      Mormon crickets were more likely to approach and attack a stationary cricket that
      was side-on to the flow than either head- or abdomen-on, suggesting that
      individuals could reduce their risk of an attack by aligning with neighbours. We
      found strong social effects on cannibalistic behaviour: encounters lasted longer,
      were more likely to result in an attack, and attacks were more likely to be
      successful if other individuals were present around a stationary individual. This
      local aggregation appears to be driven by positive feedback whereby the presence
      of individuals attracts others, which can lead to further crowding. This work
      improves our understanding of the local social dynamics driving migratory band
      formation, maintenance and movement at the population level.

PMID- 21179403
TI  - Iota-carrageenan is a potent inhibitor of influenza A virus infection.
AB  - The 2009 flu pandemic and the appearance of oseltamivir-resistant H1N1 influenza
      strains highlight the need for treatment alternatives. One such option is the
      creation of a protective physical barrier in the nasal cavity. In vitro tests
      demonstrated that iota-carrageenan is a potent inhibitor of influenza A virus
      infection, most importantly also of pandemic H1N1/2009 in vitro. Consequently, we
      tested a commercially available nasal spray containing iota-carrageenan in an
      influenza A mouse infection model. Treatment of mice infected with a lethal dose
      of influenza A PR8/34 H1N1 virus with iota-carrageenan starting up to 48 hours
      post infection resulted in a strong protection of mice similar to mice treated
      with oseltamivir. Since alternative treatment options for influenza are rare, we
      conclude that the nasal spray containing iota-carrageenan is an alternative to
      neuraminidase inhibitors and should be tested for prevention and treatment of
      influenza A in clinical trials in humans.

PMID- 21179404
TI  - Equivalence of ELISpot assays demonstrated between major HIV network
      laboratories.
AB  - BACKGROUND: The Comprehensive T Cell Vaccine Immune Monitoring Consortium (CTC
      VIMC) was created to provide standardized immunogenicity monitoring services for
      HIV vaccine trials. The ex vivo interferon-gamma (IFN-gamma) ELISpot is used
      extensively as a primary immunogenicity assay to assess T cell-based vaccine
      candidates in trials for infectious diseases and cancer. Two independent, GCLP
      accredited central laboratories of CTC-VIMC routinely use their own standard
      operating procedures (SOPs) for ELISpot within two major networks of HIV vaccine
      trials. Studies are imperatively needed to assess the comparability of ELISpot
      measurements across laboratories to benefit optimal advancement of vaccine
      candidates. METHODS: We describe an equivalence study of the two independently
      qualified IFN-g ELISpot SOPs. The study design, data collection and subsequent
      analysis were managed by independent statisticians to avoid subjectivity. The
      equivalence of both response rates and positivity calls to a given stimulus was
      assessed based on pre-specified acceptance criteria derived from a separate pilot
      study. FINDINGS: Detection of positive responses was found to be equivalent
      between both laboratories. The 95% C.I. on the difference in response rates, for
      CMV (-1.5%, 1.5%) and CEF (-0.4%, 7.8%) responses, were both contained in the pre
      specified equivalence margin of interval [-15%, 15%]. The lower bound of the 95%
      C.I. on the proportion of concordant positivity calls for CMV (97.2%) and CEF
      (89.5%) were both greater than the pre-specified margin of 70%. A third CTC-VIMC
      central laboratory already using one of the two SOPs also showed comparability
      when tested in a smaller sub-study. INTERPRETATION: The described study procedure
      provides a prototypical example for the comparison of bioanalytical methods in
      HIV vaccine and other disease fields. This study also provides valuable and
      unprecedented information for future vaccine candidate evaluations on the
      comparison and pooling of ELISpot results generated by the CTC-VIMC central core
      laboratories.

PMID- 21179405
TI  - Immunospecific responses to bacterial elongation factor Tu during Burkholderia
      infection and immunization.
AB  - Burkholderia pseudomallei is the etiological agent of melioidosis, a disease
      endemic in parts of Southeast Asia and Northern Australia. Currently there is no
      licensed vaccine against infection with this biological threat agent. In this
      study, we employed an immunoproteomic approach and identified bacterial
      Elongation factor-Tu (EF-Tu) as a potential vaccine antigen. EF-Tu is membrane
      associated, secreted in outer membrane vesicles (OMVs), and immunogenic during
      Burkholderia infection in the murine model of melioidosis. Active immunization
      with EF-Tu induced antigen-specific antibody and cell-mediated immune responses
      in mice. Mucosal immunization with EF-Tu also reduced lung bacterial loads in
      mice challenged with aerosolized B. thailandensis. Our data support the utility
      of EF-Tu as a novel vaccine immunogen against bacterial infection.

PMID- 21179407
TI  - Sex, ecology and the brain: evolutionary correlates of brain structure volumes in
      Tanganyikan cichlids.
AB  - Analyses of the macroevolutionary correlates of brain structure volumes allow
      pinpointing of selective pressures influencing specific structures. Here we use a
      multiple regression framework, including phylogenetic information, to analyze
      brain structure evolution in 43 Tanganyikan cichlid species. We analyzed the
      effect of ecological and sexually selected traits for species averages, the
      effect of ecological traits for each sex separately and the influence of sexual
      selection on structure dimorphism. Our results indicate that both ecological and
      sexually selected traits have influenced brain structure evolution. The patterns
      observed in males and females generally followed those observed at the species
      level. Interestingly, our results suggest that strong sexual selection is
      associated with reduced structure volumes, since all correlations between
      sexually selected traits and structure volumes were negative and the only
      statistically significant association between sexual selection and structure
      dimorphism was also negative. Finally, we previously found that monoparental
      female care was associated with increased brain size. However, here cerebellum
      and hypothalamus volumes, after controlling for brain size, associated negatively
      with female-only care. Thus, in accord with the mosaic model of brain evolution,
      brain structure volumes may not respond proportionately to changes in brain size.
      Indeed selection favoring larger brains can simultaneously lead to a reduction in
      relative structure volumes.

PMID- 21179408
TI  - hSAGEing: an improved SAGE-based software for identification of human tissue
      specific or common tumor markers and suppressors.
AB  - BACKGROUND: SAGE (serial analysis of gene expression) is a powerful method of
      analyzing gene expression for the entire transcriptome. There are currently many
      well-developed SAGE tools. However, the cross-comparison of different tissues is
      seldom addressed, thus limiting the identification of common- and tissue-specific
      tumor markers. METHODOLOGY/PRINCIPAL FINDINGS: To improve the SAGE mining
      methods, we propose a novel function for cross-tissue comparison of SAGE data by
      combining the mathematical set theory and logic with a unique "multi-pool method"
      that analyzes multiple pools of pair-wise case controls individually. When all
      the settings are in "inclusion", the common SAGE tag sequences are mined. When
      one tissue type is in "inclusion" and the other types of tissues are not in
      "inclusion", the selected tissue-specific SAGE tag sequences are generated. They
      are displayed in tags-per-million (TPM) and fold values, as well as visually
      displayed in four kinds of scales in a color gradient pattern. In the fold
      visualization display, the top scores of the SAGE tag sequences are provided,
      along with cluster plots. A user-defined matrix file is designed for cross-tissue
      comparison by selecting libraries from publically available databases or user
      defined libraries. CONCLUSIONS/SIGNIFICANCE: The hSAGEing tool provides a
      combination of friendly cross-tissue analysis and an interface for comparing SAGE
      libraries for the first time. Some up- or down-regulated genes with tissue
      specific or common tumor markers and suppressors are identified computationally.
      The tool is useful and convenient for in silico cancer transcriptomic studies and
      is freely available at http://bio.kuas.edu.tw/hSAGEing.

PMID- 21179406
TI  - Minimal peroxide exposure of neuronal cells induces multifaceted adaptive
      responses.
AB  - Oxidative exposure of cells occurs naturally and may be associated with cellular
      damage and dysfunction. Protracted low level oxidative exposure can induce
      accumulated cell disruption, affecting multiple cellular functions. Accumulated
      oxidative exposure has also been proposed as one of the potential hallmarks of
      the physiological/pathophysiological aging process. We investigated the
      multifactorial effects of long-term minimal peroxide exposure upon SH-SY5Y neural
      cells to understand how they respond to the continued presence of oxidative
      stressors. We show that minimal protracted oxidative stresses induce complex
      molecular and physiological alterations in cell functionality. Upon chronic
      exposure to minimal doses of hydrogen peroxide, SH-SY5Y cells displayed a
      multifactorial response to the stressor. To fully appreciate the peroxide
      mediated cellular effects, we assessed these adaptive effects at the genomic,
      proteomic and cellular signal processing level. Combined analyses of these
      multiple levels of investigation revealed a complex cellular adaptive response to
      the protracted peroxide exposure. This adaptive response involved changes in
      cytoskeletal structure, energy metabolic shifts towards glycolysis and selective
      alterations in transmembrane receptor activity. Our analyses of the global
      responses to chronic stressor exposure, at multiple biological levels, revealed a
      viable neural phenotype in-part reminiscent of aged or damaged neural tissue. Our
      paradigm indicates how cellular physiology can subtly change in different
      contexts and potentially aid the appreciation of stress response adaptations.

PMID- 21179409
TI  - Arrhythmia caused by a Drosophila tropomyosin mutation is revealed using a novel
      optical coherence tomography instrument.
AB  - BACKGROUND: Dilated cardiomyopathy (DCM) is a severe cardiac condition that
      causes high mortality. Many genes have been confirmed to be involved in this
      disease. An ideal system with which to uncover disease mechanisms would be one
      that can measure the changes in a wide range of cardiac activities associated
      with mutations in specific, diversely functional cardiac genes. Such a system
      needs a genetically manipulable model organism that allows in vivo measurement of
      cardiac phenotypes and a detecting instrument capable of recording multiple
      phenotype parameters. METHODOLOGY AND PRINCIPAL FINDINGS: With a simple heart, a
      transparent body surface at larval stages and available genetic tools we chose
      Drosophila melanogaster as our model organism and developed for it a dual en
      face/Doppler optical coherence tomography (OCT) instrument capable of recording
      multiple aspects of heart activity, including heart contraction cycle dynamics,
      ostia dynamics, heartbeat rate and rhythm, speed of heart wall movement and light
      reflectivity of cardiomyocytes in situ. We applied this OCT instrument to a model
      of Tropomyosin-associated DCM established in adult Drosophila. We show that DCM
      pre-exists in the larval stage and is accompanied by an arrhythmia previously
      unidentified in this model. We also detect reduced mobility and light
      reflectivity of cardiomyocytes in mutants. CONCLUSION: These results demonstrate
      the capability of our OCT instrument to characterize in detail cardiac activity
      in genetic models for heart disease in Drosophila.

PMID- 21179410
TI  - Alpha-syntrophin modulates myogenin expression in differentiating myoblasts.
AB  - BACKGROUND: alpha-Syntrophin is a scaffolding protein linking signaling proteins
      to the sarcolemmal dystrophin complex in mature muscle. However, alpha-syntrophin
      is also expressed in differentiating myoblasts during the early stages of muscle
      differentiation. In this study, we examined the relationship between the
      expression of alpha-syntrophin and myogenin, a key muscle regulatory factor.
      METHODS AND FINDINGS: The absence of alpha-syntrophin leads to reduced and
      delayed myogenin expression. This conclusion is based on experiments using muscle
      cells isolated from alpha-syntrophin null mice, muscle regeneration studies in
      alpha-syntrophin null mice, experiments in Sol8 cells (a cell line that expresses
      only low levels of alpha-syntrophin) and siRNA studies in differentiating C2
      cells. In primary cultured myocytes isolated from alpha-syntrophin null mice, the
      level of myogenin was less than 50% that from wild type myocytes (p<0.005) 40 h
      after differentiation induction. In regenerating muscle, the expression of
      myogenin in the alpha-syntrophin null muscle was reduced to approximately 25%
      that of wild type muscle (p<0.005). Conversely, myogenin expression is enhanced
      in primary cultures of myoblasts isolated from a transgenic mouse over-expressing
      alpha-syntrophin and in Sol8 cells transfected with a vector to over-express
      alpha-syntrophin. Moreover, we find that myogenin mRNA is reduced in the absence
      of alpha-syntrophin and increased by alpha-syntrophin over-expression.
      Immunofluorescence microscopy shows that alpha-syntrophin is localized to the
      nuclei of differentiating myoblasts. Finally, immunoprecipitation experiments
      demonstrate that alpha-syntrophin associates with Mixed-Lineage Leukemia 5, a
      regulator of myogenin expression. CONCLUSIONS: We conclude that alpha-syntrophin
      plays an important role in regulating myogenesis by modulating myogenin
      expression.

PMID- 21179411
TI  - Liposome-coupled antigens are internalized by antigen-presenting cells via
      pinocytosis and cross-presented to CD8 T cells.
AB  - We have previously demonstrated that antigens chemically coupled to the surface
      of liposomes consisting of unsaturated fatty acids were cross-presented by
      antigen-presenting cells (APCs) to CD8+ T cells, and that this process resulted
      in the induction of antigen-specific cytotoxic T lymphocytes. In the present
      study, the mechanism by which the liposome-coupled antigens were cross-presented
      to CD8+ T cells by APCs was investigated. Confocal laser scanning microscopic
      analysis demonstrated that antigens coupled to the surface of unsaturated-fatty
      acid-based liposomes received processing at both MHC class I and class II
      compartments, while most of the antigens coupled to the surface of saturated
      fatty-acid-based liposomes received processing at the class II compartment. In
      addition, flow cytometric analysis demonstrated that antigens coupled to the
      surface of unsaturated-fatty-acid-liposomes were taken up by APCs even in a 4
      degrees C environment; this was not true of saturated-fatty-acid-liposomes. When
      two kinds of inhibitors, dimethylamiloride (DMA) and cytochalasin B, which
      inhibit pinocytosis and phagocytosis by APCs, respectively, were added to the
      culture of APCs prior to the antigen pulse, DMA but not cytochalasin B
      significantly reduced uptake of liposome-coupled antigens. Further analysis of
      intracellular trafficking of liposomal antigens using confocal laser scanning
      microscopy revealed that a portion of liposome-coupled antigens taken up by APCs
      were delivered to the lysosome compartment. In agreement with the reduction of
      antigen uptake by APCs, antigen presentation by APCs was significantly inhibited
      by DMA, and resulted in the reduction of IFN-gamma production by antigen-specific
      CD8+ T cells. These results suggest that antigens coupled to the surface of
      liposomes consisting of unsaturated fatty acids might be pinocytosed by APCs,
      loaded onto the class I MHC processing pathway, and presented to CD8+ T cells.
      Thus, these liposome-coupled antigens are expected to be applicable for the
      development of vaccines that induce cellular immunity.

PMID- 21179412
TI  - Alpha-galactosylceramide analogs with weak agonist activity for human iNKT cells
      define new candidate anti-inflammatory agents.
AB  - CD1d-restricted natural killer T cells with invariant T cell receptor alpha
      chains (iNKT cells) are a unique lymphocyte subset that responds to recognition
      of specific lipid and glycolipid antigens. They are conserved between mice and
      humans and exert various immunoregulatory functions through their rapid secretion
      of a variety of cytokines and secondary activation of dendritic cells, B cells
      and NK cells. In the current study, we analyzed the range of functional
      activation states of human iNKT cells using a library of novel analogs of alpha
      galactosylceramide (alphaGalCer), the prototypical iNKT cell antigen. Measurement
      of cytokines secreted by human iNKT cell clones over a wide range of glycolipid
      concentrations revealed that iNKT cell ligands could be classified into
      functional groups, correlating with weak versus strong agonistic activity. The
      findings established a hierarchy for induction of different cytokines, with
      thresholds for secretion being consistently lowest for IL-13, higher for
      interferon-gamma (IFNgamma), and even higher for IL-4. These findings suggested
      that human iNKT cells can be intrinsically polarized to selective production of
      IL-13 by maintaining a low level of activation using weak agonists, whereas
      selective polarization to IL-4 production cannot be achieved through modulating
      the strength of the activating ligand. In addition, using a newly designed in
      vitro system to assess the ability of human iNKT cells to transactivate NK cells,
      we found that robust secondary induction of interferon-gamma secretion by NK
      cells was associated with strong but not weak agonist ligands of iNKT cells.
      These results indicate that polarization of human iNKT cell responses to Th2-like
      or anti-inflammatory effects may best be achieved through selective induction of
      IL-13 and suggest potential discrepancies with findings from mouse models that
      may be important in designing iNKT cell-based therapies in humans.

PMID- 21179413
TI  - Beta-amyloid 1-42 oligomers impair function of human embryonic stem cell-derived
      forebrain cholinergic neurons.
AB  - Cognitive impairment in Alzheimer's disease (AD) patients is associated with a
      decline in the levels of growth factors, impairment of axonal transport and
      marked degeneration of basal forebrain cholinergic neurons (BFCNs). Neurogenesis
      persists in the adult human brain, and the stimulation of regenerative processes
      in the CNS is an attractive prospect for neuroreplacement therapy in
      neurodegenerative diseases such as AD. Currently, it is still not clear how the
      pathophysiological environment in the AD brain affects stem cell biology.
      Previous studies investigating the effects of the beta-amyloid (Abeta) peptide on
      neurogenesis have been inconclusive, since both neurogenic and neurotoxic effects
      on progenitor cell populations have been reported. In this study, we treated
      pluripotent human embryonic stem (hES) cells with nerve growth factor (NGF) as
      well as with fibrillar and oligomeric Abeta1-40 and Abeta1-42 (nM-uM
      concentrations) and thereafter studied the differentiation in vitro during 28-35
      days. The process applied real time quantitative PCR, immunocytochemistry as well
      as functional studies of intracellular calcium signaling. Treatment with NGF
      promoted the differentiation into functionally mature BFCNs. In comparison to
      untreated cells, oligomeric Abeta1-40 increased the number of functional neurons,
      whereas oligomeric Abeta1-42 suppressed the number of functional neurons.
      Interestingly, oligomeric Abeta exposure did not influence the number of hES cell
      derived neurons compared with untreated cells, while in contrast fibrillar Abeta1
      40 and Abeta1-42 induced gliogenesis. These findings indicate that Abeta1-42
      oligomers may impair the function of stem cell-derived neurons. We propose that
      it may be possible for future AD therapies to promote the maturation of
      functional stem cell-derived neurons by altering the brain microenvironment with
      trophic support and by targeting different aggregation forms of Abeta.

PMID- 21179414
TI  - Characterization of protective human CD4CD25 FOXP3 regulatory T cells generated
      with IL-2, TGF-beta and retinoic acid.
AB  - BACKGROUND: Protective CD4+CD25+ regulatory T cells bearing the Forkhead Foxp3
      transcription factor can now be divided into three subsets: Endogenous thymus
      derived cells, those induced in the periphery, and another subset induced ex-vivo
      with pharmacological amounts of IL-2 and TGF-beta. Unfortunately, endogenous
      CD4+CD25+ regulatory T cells are unstable and can be converted to effector cells
      by pro-inflammatory cytokines. Although protective Foxp3+CD4+CD25+ cells
      resistant to proinflammatory cytokines have been generated in mice, in humans
      this result has been elusive. Our objective, therefore, was to induce human naive
      CD4+ cells to become stable, functional CD25+ Foxp3+ regulatory cells that were
      also resistant to the inhibitory effects of proinflammatory cytokines.
      METHODOLOGY/PRINCIPAL FINDINGS: The addition of the vitamin A metabolite, all
      trans retinoic acid (atRA) to human naive CD4+ cells suboptimally activated with
      IL-2 and TGF-beta enhanced and stabilized FOXP3 expression, and accelerated their
      maturation to protective regulatory T cells. AtRA, by itself, accelerated
      conversion of naive to mature cells but did not induce FOXP3 or suppressive
      activity. The combination of atRA and TGF-beta enabled CD4+CD45RA+ cells to
      express a phenotype and trafficking receptors similar to natural Tregs. AtRA/TGF
      beta-induced CD4+ regs were anergic and low producers of IL-2. They had potent in
      vitro suppressive activity and protected immunodeficient mice from a human-anti
      mouse GVHD as well as expanded endogenous Tregs. However, treatment of endogenous
      Tregs with IL-1beta and IL-6 decreased FOXP3 expression and diminished their
      protective effects in vivo while atRA-induced iTregs were resistant to these
      inhibitory effects. CONCLUSIONS/SIGNIFICANCE: We have developed a methodology
      that induces human CD4(+) cells to rapidly become stable, fully functional
      suppressor cells that are also resistant to proinflammatory cytokines. This
      methodology offers a practical novel strategy to treat human autoimmune diseases
      and prevent allograft rejection without the use of agents that kill cells or
      interfere with signaling pathways.

PMID- 21179415
TI  - Zinc overload enhances APP cleavage and Abeta deposition in the Alzheimer mouse
      brain.
AB  - BACKGROUND: Abnormal zinc homeostasis is involved in beta-amyloid (Abeta) plaque
      formation and, therefore, the zinc load is a contributing factor in Alzheimer's
      disease (AD). However, the involvement of zinc in amyloid precursor protein (APP)
      processing and Abeta deposition has not been well established in AD animal models
      in vivo. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, APP and presenilin
      1 (PS1) double transgenic mice were treated with a high dose of zinc (20 mg/ml
      ZnSO4 in drinking water). This zinc treatment increased APP expression, enhanced
      amyloidogenic APP cleavage and Abeta deposition, and impaired spatial learning
      and memory in the transgenic mice. We further examined the effects of zinc
      overload on APP processing in SHSY-5Y cells overexpressing human APPsw. The zinc
      enhancement of APP expression and cleavage was further confirmed in vitro.
      CONCLUSIONS/SIGNIFICANCE: The present data indicate that excess zinc exposure
      could be a risk factor for AD pathological processes, and alteration of zinc
      homeostasis is a potential strategy for the prevention and treatment of AD.

PMID- 21179416
TI  - C-terminal moiety of Tudor contains its in vivo activity in Drosophila.
AB  - BACKGROUND: In early Drosophila embryos, the germ plasm is localized to the
      posterior pole region and is partitioned into the germline progenitors, known as
      pole cells. Germ plasm, or pole plasm, contains the polar granules which form
      during oogenesis and are required for germline development. Components of these
      granules are also present in the perinuclear region of the nurse cells, the
      nuage. One such component is Tudor (Tud) which is a large protein containing
      multiple Tudor domains. It was previously reported that specific Tudor domains
      are required for germ cell formation and Tud localization. METHODOLOGY/PRINCIPAL
      FINDINGS: In order to better understand the function of Tud the distribution and
      functional activity of fragments of Tud were analyzed. These fragments were fused
      to GFP and the fusion proteins were synthesized during oogenesis. Non-overlapping
      fragments of Tud were found to be able to localize to both the nuage and pole
      plasm. By introducing these fragments into a tud mutant background and testing
      their ability to rescue the tud phenotype, I determined that the C-terminal
      moiety contains the functional activity of Tud. Dividing this fragment into two
      parts reduces its localization in pole plasm and abolishes its activity.
      CONCLUSIONS/SIGNIFICANCE: I conclude that the C-terminal moiety of Tud contains
      all the information necessary for its localization in the nuage and pole plasm
      and its pole cell-forming activity. The present results challenge published data
      and may help refining the functional features of Tud.

PMID- 21179417
TI  - Accuracy of Doppler-echocardiographic mean pulmonary artery pressure for
      diagnosis of pulmonary hypertension.
AB  - BACKGROUND: The validity of Doppler echocardiographic (DE) measurement of
      systolic pulmonary artery pressure (sPAP) has been questioned. Recent studies
      suggest that mean pulmonary artery pressure (mPAP) might reflect more accurately
      the invasive pressures. METHODOLOGY/PRINCIPAL FINDINGS: 241 patients were
      prospectively studied to evaluate the diagnostic accuracy of mPAP for the
      diagnosis of PH. Right heart catheterization (RHC) and DE were performed in 164
      patients mainly for preoperative evaluation of heart valve dysfunction. The
      correlation between DE and RHC was better when mPAP (r=0.93) and not sPAP
      (r=0.81) was assessed. Bland-Altman analysis revealed a smaller variation of mPAP
      than sPAP. The following ROC analysis identified that a mPAP>=25.5 mmHg is useful
      for the diagnosis of PH. This value was validated in an independent cohort of
      patients (n=50) with the suspicion of chronic-thromboembolic pulmonary
      hypertension. The calculated diagnostic accuracy was 98%, based on excellent
      sensitivity of 98% and specificity of 100%. The corresponding positive and
      negative predictive values were 100%, respectively 88%. CONCLUSION: mPAP has been
      found to be highly accurate for the initial diagnosis of PH. A cut-off value of
      25.5 mmHg might be helpful to avoid unnecessary RHC and select patients in whom
      RHC might be beneficial.

PMID- 21179418
TI  - Modeling effects of local extinctions on culture change and diversity in the
      paleolithic.
AB  - The persistence of early stone tool technologies has puzzled archaeologists for
      decades. Cognitively based explanations, which presume either lack of ability to
      innovate or extreme conformism, do not account for the totality of the empirical
      patterns. Following recent research, this study explores the effects of
      demographic factors on rates of culture change and diversification. We
      investigate whether the appearance of stability in early Paleolithic technologies
      could result from frequent extinctions of local subpopulations within a
      persistent metapopulation. A spatially explicit agent-based model was constructed
      to test the influence of local extinction rate on three general cultural patterns
      that archaeologists might observe in the material record: total diversity,
      differentiation among spatially defined groups, and the rate of cumulative
      change. The model shows that diversity, differentiation, and the rate of
      cumulative cultural change would be strongly affected by local extinction rates,
      in some cases mimicking the results of conformist cultural transmission. The
      results have implications for understanding spatial and temporal patterning in
      ancient material culture.

PMID- 21179420
TI  - Role of the Yersinia pestis yersiniabactin iron acquisition system in the
      incidence of flea-borne plague.
AB  - Plague is a flea-borne zoonosis caused by the bacterium Yersinia pestis. Y.
      pestis mutants lacking the yersiniabactin (Ybt) siderophore-based iron transport
      system are avirulent when inoculated intradermally but fully virulent when
      inoculated intravenously in mice. Presumably, Ybt is required to provide
      sufficient iron at the peripheral injection site, suggesting that Ybt would be an
      essential virulence factor for flea-borne plague. Here, using a flea-to-mouse
      transmission model, we show that a Y. pestis strain lacking the Ybt system causes
      fatal plague at low incidence when transmitted by fleas. Bacteriology and
      histology analyses revealed that a Ybt-negative strain caused only primary
      septicemic plague and atypical bubonic plague instead of the typical bubonic form
      of disease. The results provide new evidence that primary septicemic plague is a
      distinct clinical entity and suggest that unusual forms of plague may be caused
      by atypical Y. pestis strains.

PMID- 21179419
TI  - A method for generation of bone marrow-derived macrophages from cryopreserved
      mouse bone marrow cells.
AB  - The broad use of transgenic and gene-targeted mice has established bone marrow
      derived macrophages (BMDM) as important mammalian host cells for investigation of
      the macrophages biology. Over the last decade, extensive research has been done
      to determine how to freeze and store viable hematopoietic human cells; however,
      there is no information regarding generation of BMDM from frozen murine bone
      marrow (BM) cells. Here, we establish a highly efficient protocol to freeze
      murine BM cells and further generate BMDM. Cryopreserved murine BM cells maintain
      their potential for BMDM differentiation for more than 6 years. We compared BMDM
      obtained from fresh and frozen BM cells and found that both are similarly able to
      trigger the expression of CD80 and CD86 in response to LPS or infection with the
      intracellular bacteria Legionella pneumophila. Additionally, BMDM obtained from
      fresh or frozen BM cells equally restrict or support the intracellular
      multiplication of pathogens such as L. pneumophila and the protozoan parasite
      Leishmania (L.) amazonensis. Although further investigation are required to
      support the use of the method for generation of dendritic cells, preliminary
      experiments indicate that bone marrow-derived dendritic cells can also be
      generated from cryopreserved BM cells. Overall, the method described and
      validated herein represents a technical advance as it allows ready and easy
      generation of BMDM from a stock of frozen BM cells.

PMID- 21179421
TI  - Minor and unsystematic cortical topographic changes of attention correlates
      between modalities.
AB  - In this study we analyzed the topography of induced cortical oscillations in 20
      healthy individuals performing simple attention tasks. We were interested in
      qualitatively replicating our recent findings on the localization of attention
      induced beta bands during a visual task [1], and verifying whether significant
      topographic changes would follow the change of attention to the auditory
      modality. We computed corrected latency averaging of each induced frequency
      bands, and modeled their generators by current density reconstruction with Lp
      norm minimization. We quantified topographic similarity between conditions by an
      analysis of correlations, whereas the inter-modality significant differences in
      attention correlates were illustrated in each individual case. We replicated the
      qualitative result of highly idiosyncratic topography of attention-related
      activity to individuals, manifested both in the beta bands, and previously
      studied slow potential distributions [2]. Visual inspection of both scalp
      potentials and distribution of cortical currents showed minor changes in
      attention-related bands with respect to modality, as compared to the theta and
      delta bands, known to be major contributors to the sensory-related potentials.
      Quantitative results agreed with visual inspection, supporting to the conclusion
      that attention-related activity does not change much between modalities, and
      whatever individual changes do occur, they are not systematic in cortical
      localization across subjects. We discuss our results, combined with results from
      other studies that present individual data, with respect to the function of
      cortical association areas.

PMID- 21179422
TI  - Exosomes communicate protective messages during oxidative stress; possible role
      of exosomal shuttle RNA.
AB  - BACKGROUND: Exosomes are small extracellular nanovesicles of endocytic origin
      that mediate different signals between cells, by surface interactions and by
      shuttling functional RNA from one cell to another. Exosomes are released by many
      cells including mast cells, dendritic cells, macrophages, epithelial cells and
      tumour cells. Exosomes differ compared to their donor cells, not only in size,
      but also in their RNA, protein and lipid composition. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, we show that exosomes, released by mouse mast cells
      exposed to oxidative stress, differ in their mRNA content. Also, we show that
      these exosomes can influence the response of other cells to oxidative stress by
      providing recipient cells with a resistance against oxidative stress, observed as
      an attenuated loss of cell viability. Furthermore, Affymetrix microarray analysis
      revealed that the exosomal mRNA content not only differs between exosomes and
      donor cells, but also between exosomes derived from cells grown under different
      conditions; oxidative stress and normal conditions. Finally, we also show that
      exposure to UV-light affects the biological functions associated with exosomes
      released under oxidative stress. CONCLUSIONS/SIGNIFICANCE: These results argue
      that the exosomal shuttle of RNA is involved in cell-to-cell communication, by
      influencing the response of recipient cells to an external stress stimulus.

PMID- 21179423
TI  - Eu-social science: the role of internet social networks in the collection of bee
      biodiversity data.
AB  - BACKGROUND: Monitoring change in species diversity, community composition and
      phenology is vital to assess the impacts of anthropogenic activity and natural
      change. However, monitoring by trained scientists is time consuming and
      expensive. METHODOLOGY/PRINCIPAL FINDINGS: Using social networks, we assess
      whether it is possible to obtain accurate data on bee distribution across the UK
      from photographic records submitted by untrained members of the public, and if
      these data are in sufficient quantity for ecological studies. We used Flickr and
      Facebook as social networks and Flickr for the storage of photographs and
      associated data on date, time and location linked to them. Within six weeks, the
      number of pictures uploaded to the Flickr BeeID group exceeded 200. Geographic
      coverage was excellent; the distribution of photographs covered most of the
      British Isles, from the south coast of England to the Highlands of Scotland.
      However, only 59% of photographs were properly uploaded according to
      instructions, with vital information such as 'tags' or location information
      missing from the remainder. Nevertheless, this incorporation of information on
      location of photographs was much higher than general usage on Flickr (~13%),
      indicating the need for dedicated projects to collect spatial ecological data.
      Furthermore, we found identification of bees is not possible from all
      photographs, especially those excluding lower abdomen detail. This suggests that
      giving details regarding specific anatomical features to include on photographs
      would be useful to maximise success. CONCLUSIONS/SIGNIFICANCE: The study
      demonstrates the power of social network sites to generate public interest in a
      project and details the advantages of using a group within an existing popular
      social network site over a traditional (specifically-designed) web-based or paper
      based submission process. Some advantages include the ability to network with
      other individuals or groups with similar interests, and thus increasing the size
      of the dataset and participation in the project.

PMID- 21179425
TI  - Diversity of beetle genes encoding novel plant cell wall degrading enzymes.
AB  - Plant cell walls are a heterogeneous mixture of polysaccharides and proteins that
      require a range of different enzymes to degrade them. Plant cell walls are also
      the primary source of cellulose, the most abundant and useful biopolymer on the
      planet. Plant cell wall degrading enzymes (PCWDEs) are therefore important in a
      wide range of biotechnological processes from the production of biofuels and food
      to waste processing. However, despite the fact that the last common ancestor of
      all deuterostomes was inferred to be able to digest, or even synthesize,
      cellulose using endogenous genes, all model insects whose complete genomes have
      been sequenced lack genes encoding such enzymes. To establish if the apparent
      "disappearance" of PCWDEs from insects is simply a sampling problem, we used 454
      mediated pyrosequencing to scan the gut transcriptomes of beetles that feed on a
      variety of plant derived diets. By sequencing the transcriptome of five beetles,
      and surveying publicly available ESTs, we describe 167 new beetle PCWDEs
      belonging to eight different enzyme families. This survey proves that these
      enzymes are not only present in non-model insects but that the multigene families
      that encode them are apparently undergoing complex birth-death dynamics. This
      reinforces the observation that insects themselves, and not just their microbial
      symbionts, are a rich source of PCWDEs. Further it emphasises that the apparent
      absence of genes encoding PCWDEs from model organisms is indeed simply a sampling
      artefact. Given the huge diversity of beetles alive today, and the diversity of
      their lifestyles and diets, we predict that beetle guts will emerge as an
      important new source of enzymes for use in biotechnology.

PMID- 21179424
TI  - A second-generation device for automated training and quantitative behavior
      analyses of molecularly-tractable model organisms.
AB  - A deep understanding of cognitive processes requires functional, quantitative
      analyses of the steps leading from genetics and the development of nervous system
      structure to behavior. Molecularly-tractable model systems such as Xenopus laevis
      and planaria offer an unprecedented opportunity to dissect the mechanisms
      determining the complex structure of the brain and CNS. A standardized platform
      that facilitated quantitative analysis of behavior would make a significant
      impact on evolutionary ethology, neuropharmacology, and cognitive science. While
      some animal tracking systems exist, the available systems do not allow automated
      training (feedback to individual subjects in real time, which is necessary for
      operant conditioning assays). The lack of standardization in the field, and the
      numerous technical challenges that face the development of a versatile system
      with the necessary capabilities, comprise a significant barrier keeping molecular
      developmental biology labs from integrating behavior analysis endpoints into
      their pharmacological and genetic perturbations. Here we report the development
      of a second-generation system that is a highly flexible, powerful machine vision
      and environmental control platform. In order to enable multidisciplinary studies
      aimed at understanding the roles of genes in brain function and behavior, and aid
      other laboratories that do not have the facilities to undergo complex engineering
      development, we describe the device and the problems that it overcomes. We also
      present sample data using frog tadpoles and flatworms to illustrate its use.
      Having solved significant engineering challenges in its construction, the
      resulting design is a relatively inexpensive instrument of wide relevance for
      several fields, and will accelerate interdisciplinary discovery in pharmacology,
      neurobiology, regenerative medicine, and cognitive science.

PMID- 21179426
TI  - The therapeutic implications of plasticity of the cancer stem cell phenotype.
AB  - The cancer stem cell hypothesis suggests that tumors contain a small population
      of cancer cells that have the ability to undergo symmetric self-renewing cell
      division. In tumors that follow this model, cancer stem cells produce various
      kinds of specified precursors that divide a limited number of times before
      terminally differentiating or undergoing apoptosis. As cells within the tumor
      mature, they become progressively more restricted in the cell types to which they
      can give rise. However, in some tumor types, the presence of certain extra- or
      intracellular signals can induce committed cancer progenitors to revert to a
      multipotential cancer stem cell state. In this paper, we design a novel
      mathematical model to investigate the dynamics of tumor progression in such
      situations, and study the implications of a reversible cancer stem cell phenotype
      for therapeutic interventions. We find that higher levels of dedifferentiation
      substantially reduce the effectiveness of therapy directed at cancer stem cells
      by leading to higher rates of resistance. We conclude that plasticity of the
      cancer stem cell phenotype is an important determinant of the prognosis of
      tumors. This model represents the first mathematical investigation of this tumor
      trait and contributes to a quantitative understanding of cancer.

PMID- 21179427
TI  - CyclinD1 protein expressed in pterygia is associated with beta-catenin protein
      localization.
AB  - BACKGROUND: The Wnt (Wg/Wnt) signaling cascade plays an important role in
      tumorigenesis. Our previous report indicated that aberrant localization of beta
      catenin proteins was a feature of pterygia. Therefore, this study aimed to
      analyze the association of beta-catenin protein and expression of a downstream
      gene, cyclin D1, in pterygial tissues. METHODS: Using immunohistochemistry, beta
      catenin and cyclin D1 protein expression was studied, in 150 pterygial specimens
      and 30 normal conjunctivas. RESULTS: Seventy-three (48.7%) and 60 (40.0%)
      pterygial specimens tested positive for beta-catenin and cyclin D1 protein
      expression, respectively. Cyclin D1protein expression was significantly higher in
      beta-catenin-nuclear/cytoplasmic positive groups than in beta-catenin membrane
      positive and negative groups (p < 0.0001). In addition, cyclin D1 expression was
      significantly higher in the fleshy group than in the atrophic and intermediate
      groups (p = 0.006). CONCLUSIONS: Our study demonstrated that beta-catenin
      expressed in nuclei/cytoplasm increases cyclinD1 protein expression, which
      invokes pterygial cell proliferation.

PMID- 21179428
TI  - The effect of nerve growth factor on differentiation of corneal limbal epithelial
      cells to conjunctival goblet cells in vitro.
AB  - PURPOSE: To evaluate in vitro the effect of nerve growth factor (NGF) on the
      differentiation of mouse corneal limbal progenitor cells into goblet cells and to
      observe the expression of mucin-5AC (MUC5AC) mRNA. METHODS: Mouse limbal
      epithelial cells were cultured in a 1:1 mixture of Dulbecco's modified Eagle's
      medium/Ham's nutrient mixture F12 in vitro, and 63-kDa protein (p63) in cultured
      cells was identified with immunofluorescence staining. Different groups of the
      cultured cells were exposed to NGF at different concentrations (0 ng/ml, 10
      ng/ml, 100 ng/ml, and 250 ng/ml). MUC5AC gene expression (real-time PCR) and
      goblet cell differentiation (MUC5AC immunofluorescence staining) were analyzed at
      different time points (24 h, 72 h, and 5 d). RESULTS: In primary culture, the
      limbal epithelial cells were compact, uniform, and cobblestone pavement in shape.
      Some limbal epithelial cells were positive for p63. The MUC5AC-positive cells
      were detected when the cells were treated with 100 ng/ml NGF at each time point
      and with 250 ng/ml NGF at 5 d. The expression of MUC5AC mRNA increased when using
      100 ng/ml NGF. The MUC5AC-positive cells were not detected when 0 ng/ml and 10
      ng/ml NGF were used at each time point. CONCLUSIONS: The results of this study
      suggest that NGF might promote the differentiation of corneal limbal progenitor
      cells into conjunctival goblet cells and upregulate the expression of MUC5AC mRNA
      in primary culture. Further studies using an animal model in vivo are needed.

PMID- 21179429
TI  - Physiological expression of lens alpha-, beta-, and gamma-crystallins in murine
      and human corneas.
AB  - PURPOSE: How corneal transparency is formed/maintained remains largely unclear. A
      group of enzymes which are referred to as enzymatic crystallins were proposed to
      contribute to corneal transparency in various animals. This study investigated
      whether the three classical lens crystallins, namely alpha-, beta-, and gamma
      crystallins, exist in mouse and human corneas. METHODS: Mice, human tissues, and
      cultured corneal cells were studied. The expression of lens crystallins in
      corneas or in cultured corneal cells were detected at the mRNA level by
      quantitative reverse transcription-PCR (QRT-PCR) and at the protein level by
      immunohistochemistry or western blotting. To check the effect of exogenous factor
      on expression of lens crystallins, cultured corneal cells were challenged with
      lipopolysaccharide or hydrogen peroxide and the expression of lens crystallins
      was monitored. RESULTS: QRT-PCR revealed that the relative expression level of
      lens crystallins in C57BL/6 corneas were higher than in Balb/c corneas.
      Immunohistochemistry study showed that expression of alphaA-crystallin started
      from the embryonic stage, lasted untill old age, and was largely restricted to
      the epithelium or endothelium of the corneas. beta- and gamma-crystallins also
      were found in murine corneal epithelium. Upon treatment with lipopolysaccharide
      or hydrogen peroxide of cultured corneal epithelial cells, lens crystallins
      expression was significantly increased as detected by QRT-PCR or western blot
      assay. Further, both fetal corneal epithelial cultures and limbal stem cell
      cultures from adult human tissues were positive for lens crystallin
      immunofluorescence or immunohistochemistry staining. CONCLUSIONS: Lens
      crystallins are expressed in mammalian corneas and cultured corneal cells. The
      expression levels depended on the animal strains or cell status. The physiologic
      and pathological significance of lens crystallins in corneas deserves more
      investigation.

PMID- 21179430
TI  - Missense mutations at homologous positions in the fourth and fifth laminin A G
      like domains of eyes shut homolog cause autosomal recessive retinitis pigmentosa.
AB  - PURPOSE: To describe two novel mutations in the eyes shut homolog (EYS) gene in
      two families with autosomal recessive retinitis pigmentosa (arRP) from Pakistan
      and Indonesia. METHODS: Genome-wide linkage and homozygosity mapping were
      performed using single nucleotide polymorphism microarray analysis in affected
      members of the two arRP families. Sequence analysis was performed to identify
      genetic changes in protein coding exons of EYS. RESULTS: In the Indonesian and
      Pakistani families, homozygous regions encompassing the EYS gene at 6q12 were
      identified, with maximum LOD scores of 1.8 and 3.6, respectively. Novel missense
      variants in the EYS gene (p.D2767Y and p.D3028Y) were found in the Pakistani and
      Indonesian families, respectively, that co-segregate with the disease phenotype.
      Interestingly, the missense variants are located at the same homologous position
      within the fourth and fifth laminin A G-like domains of EYS. CONCLUSIONS: To
      date, mostly protein-truncating mutations have been described in EYS, while only
      few patients have been described with pathogenic compound heterozygous missense
      mutations. The mutations p.D2767Y and p.D3028Y described in this study affect
      highly conserved residues at homologous positions in laminin A G-like domains and
      support the notion that missense mutations in EYS can cause arRP.

PMID- 21179432
TI  - Protein keeps adjacent tissues growing in synchrony.

PMID- 21179431
TI  - Genes but not genomes reveal bacterial domestication of Lactococcus lactis.
AB  - BACKGROUND: The population structure and diversity of Lactococcus lactis subsp.
      lactis, a major industrial bacterium involved in milk fermentation, was
      determined at both gene and genome level. Seventy-six lactococcal isolates of
      various origins were studied by different genotyping methods and thirty-six
      strains displaying unique macrorestriction fingerprints were analyzed by a new
      multilocus sequence typing (MLST) scheme. This gene-based analysis was compared
      to genomic characteristics determined by pulsed-field gel electrophoresis (PFGE).
      METHODOLOGY/PRINCIPAL FINDINGS: The MLST analysis revealed that L. lactis subsp.
      lactis is essentially clonal with infrequent intra- and intergenic recombination;
      also, despite its taxonomical classification as a subspecies, it displays a
      genetic diversity as substantial as that within several other bacterial species.
      Genome-based analysis revealed a genome size variability of 20%, a value typical
      of bacteria inhabiting different ecological niches, and that suggests a large pan
      genome for this subspecies. However, the genomic characteristics
      (macrorestriction pattern, genome or chromosome size, plasmid content) did not
      correlate to the MLST-based phylogeny, with strains from the same sequence type
      (ST) differing by up to 230 kb in genome size. CONCLUSION/SIGNIFICANCE: The gene
      based phylogeny was not fully consistent with the traditional classification into
      dairy and non-dairy strains but supported a new classification based on
      ecological separation between "environmental" strains, the main contributors to
      the genetic diversity within the subspecies, and "domesticated" strains, subject
      to recent genetic bottlenecks. Comparison between gene- and genome-based analyses
      revealed little relationship between core and dispensable genome phylogenies,
      indicating that clonal diversification and phenotypic variability of the
      "domesticated" strains essentially arose through substantial genomic flux within
      the dispensable genome.

PMID- 21179433
TI  - A dp53-dependent mechanism involved in coordinating tissue growth in Drosophila.
AB  - Coordination of growth between and within organs contributes to the generation of
      well-proportioned organs and functionally integrated adults. The mechanisms that
      help to coordinate the growth between different organs start to be unravelled.
      However, whether an organ is able to respond in a coordinated manner to local
      variations in growth caused by developmental or environmental stress and the
      nature of the underlying molecular mechanisms that contribute to generating well
      proportioned adult organs under these circumstances remain largely unknown. By
      reducing the growth rates of defined territories in the developing wing
      primordium of Drosophila, we present evidence that the tissue responds as a whole
      and the adjacent cell populations decrease their growth and proliferation rates.
      This non-autonomous response occurs independently of where growth is affected,
      and it is functional all throughout development and contributes to generate well
      proportioned adult structures. Strikingly, we underscore a central role of
      Drosophila p53 (dp53) and the apoptotic machinery in these processes. While
      activation of dp53 in the growth-depleted territory mediates the non-autonomous
      regulation of growth and proliferation rates, effector caspases have a unique
      role, downstream of dp53, in reducing proliferation rates in adjacent cell
      populations. These new findings indicate the existence of a stress response
      mechanism involved in the coordination of tissue growth between adjacent cell
      populations and that tissue size and cell cycle proliferation can be uncoupled
      and are independently and non-autonomously regulated by dp53.

PMID- 21179434
TI  - Antibiotic selection pressure and macrolide resistance in nasopharyngeal
      Streptococcus pneumoniae: a cluster-randomized clinical trial.
AB  - BACKGROUND: It is widely thought that widespread antibiotic use selects for
      community antibiotic resistance, though this has been difficult to prove in the
      setting of a community-randomized clinical trial. In this study, we used a
      randomized clinical trial design to assess whether macrolide resistance was
      higher in communities treated with mass azithromycin for trachoma, compared to
      untreated control communities. METHODS AND FINDINGS: In a cluster-randomized
      trial for trachoma control in Ethiopia, 12 communities were randomized to receive
      mass azithromycin treatment of children aged 1-10 years at months 0, 3, 6, and 9.
      Twelve control communities were randomized to receive no antibiotic treatments
      until the conclusion of the study. Nasopharyngeal swabs were collected from
      randomly selected children in the treated group at baseline and month 12, and in
      the control group at month 12. Antibiotic susceptibility testing was performed on
      Streptococcus pneumoniae isolated from the swabs using Etest strips. In the
      treated group, the mean prevalence of azithromycin resistance among all monitored
      children increased from 3.6% (95% confidence interval [CI] 0.8%-8.9%) at
      baseline, to 46.9% (37.5%-57.5%) at month 12 (p = 0.003). In control communities,
      azithromycin resistance was 9.2% (95% CI 6.7%-13.3%) at month 12, significantly
      lower than the treated group (p < 0.0001). Penicillin resistance was identified
      in 0.8% (95% CI 0%-4.2%) of isolates in the control group at 1 year, and in no
      isolates in the children-treated group at baseline or 1 year. CONCLUSIONS: This
      cluster-randomized clinical trial demonstrated that compared to untreated control
      communities, nasopharyngeal pneumococcal resistance to macrolides was
      significantly higher in communities randomized to intensive azithromycin
      treatment. Mass azithromycin distributions were given more frequently than
      currently recommended by the World Health Organization's trachoma program.
      Azithromycin use in this setting did not select for resistance to penicillins,
      which remain the drug of choice for pneumococcal infections. TRIAL REGISTRATION:
      www.ClinicalTrials.gov NCT00322972. Please see later in the article for the
      Editors' Summary.

PMID- 21179435
TI  - Impact of reference gene selection for target gene normalization on experimental
      outcome using real-time qRT-PCR in adipocytes.
AB  - BACKGROUND: With the current rise in obesity-related morbidities, real-time
      quantitative reverse transcription polymerase chain reaction (qRT-PCR) has become
      a widely used method for assessment of genes expressed and regulated by
      adipocytes. In order to measure accurate changes in relative gene expression and
      monitor intersample variability, normalization to endogenous control genes that
      do not change in relative expression is commonly used with qRT-PCR
      determinations. However, historical evidence has clearly demonstrated that the
      expression profiles of traditional control genes (e.g., beta-actin, GAPDH, alpha
      tubulin) are differentially regulated across multiple tissue types and
      experimental conditions. METHODOLOGY/PRINCIPAL FINDINGS: Therefore, we validated
      six commonly used endogenous control genes under diverse experimental conditions
      of inflammatory stress, oxidative stress, synchronous cell cycle progression and
      cellular differentiation in 3T3-L1 adipocytes using TaqMan qRT-PCR. Under each
      study condition, we further evaluated the impact of reference gene selection on
      experimental outcome using examples of target genes relevant to adipocyte
      function and differentiation. We demonstrate that multiple reference genes are
      regulated in a condition-specific manner that is not suitable for use in target
      gene normalization. CONCLUSION/SIGNIFICANCE: Data are presented demonstrating
      that inappropriate reference gene selection can have profound influence on study
      conclusions ranging from divergent statistical outcome to inaccurate data
      interpretation of significant magnitude. This study validated the use of
      endogenous controls in 3T3-L1 adipocytes and highlights the impact of
      inappropriate reference gene selection on data interpretation and study
      conclusions.

PMID- 21179436
TI  - Alien hand syndrome: neural correlates of movements without conscious will.
AB  - BACKGROUND: The alien hand syndrome is a striking phenomenon characterized by
      purposeful and autonomous movements that are not voluntarily initiated. This
      study aimed to examine neural correlates of this rare neurological disorder in a
      patient with corticobasal degeneration and alien hand syndrome of the left hand.
      METHODOLOGY/PRINCIPAL FINDINGS: We employed functional magnetic resonance imaging
      to investigate brain responses associated with unwanted movements in a case
      study. Results revealed that alien hand movements involved a network of brain
      activations including the primary motor cortex, premotor cortex, precuneus, and
      right inferior frontal gyrus. Conscious and voluntary movements of the alien hand
      elicited a similar network of brain responses but lacked an activation of the
      inferior frontal gyrus. The results demonstrate that alien and unwanted movements
      may engage similar brain networks than voluntary movements, but also imply
      different functional contributions of prefrontal areas. Since the inferior
      frontal gyrus was uniquely activated during alien movements, the results provide
      further support for a specific role of this brain region in inhibitory control
      over involuntary motor responses. CONCLUSIONS/SIGNIFICANCE: We discuss the
      outcome of this study as providing evidence for a distributed neural network
      associated with unwanted movements in alien hand syndrome, including brain
      regions known to be related to movement execution and planning as well as areas
      that have been linked to inhibition control (inferior frontal gyrus) and
      experience of agency (precuneus).

PMID- 21179437
TI  - Expression QTL modules as functional components underlying higher-order
      phenotypes.
AB  - Systems genetics studies often involve the mapping of numerous regulatory
      relations between genetic loci and expression traits. These regulatory relations
      form a bipartite network consisting of genetic loci and expression phenotypes.
      Modular network organizations may arise from the pleiotropic and polygenic
      regulation of gene expression. Here we analyzed the expression QTL (eQTL)
      networks derived from expression genetic data of yeast and mouse liver and found
      65 and 98 modules respectively. Computer simulation result showed that such
      modules rarely occurred in randomized networks with the same number of nodes and
      edges and same degree distribution. We also found significant within-module
      functional coherence. The analysis of genetic overlaps and the evidences from
      biomedical literature have linked some eQTL modules to physiological phenotypes.
      Functional coherence within the eQTL modules and genetic overlaps between the
      modules and physiological phenotypes suggests that eQTL modules may act as
      functional units underlying the higher-order phenotypes.

PMID- 21179438
TI  - Hijacking of the pleiotropic cytokine interferon-gamma by the type III secretion
      system of Yersinia pestis.
AB  - Yersinia pestis, the causative agent of bubonic plague, employs its type III
      secretion system to inject toxins into target cells, a crucial step in infection
      establishment. LcrV is an essential component of the T3SS of Yersinia spp, and is
      able to associate at the tip of the secretion needle and take part in the
      translocation of anti-host effector proteins into the eukaryotic cell cytoplasm.
      Upon cell contact, LcrV is also released into the surrounding medium where it has
      been shown to block the normal inflammatory response, although details of this
      mechanism have remained elusive. In this work, we reveal a key aspect of the
      immunomodulatory function of LcrV by showing that it interacts directly and with
      nanomolar affinity with the inflammatory cytokine IFNgamma. In addition, we
      generate specific IFNgamma mutants that show decreased interaction capabilities
      towards LcrV, enabling us to map the interaction region to two basic C-terminal
      clusters of IFNgamma. Lastly, we show that the LcrV-IFNgamma interaction can be
      disrupted by a number of inhibitors, some of which display nanomolar affinity.
      This study thus not only identifies novel potential inhibitors that could be
      developed for the control of Yersinia-induced infection, but also highlights the
      diversity of the strategies used by Y. pestis to evade the immune system, with
      the hijacking of pleiotropic cytokines being a long-range mechanism that
      potentially plays a key role in the severity of plague.

PMID- 21179439
TI  - VKORC1 common variation and bone mineral density in the Third National Health and
      Nutrition Examination Survey.
AB  - Osteoporosis, defined by low bone mineral density (BMD), is common among
      postmenopausal women. The distribution of BMD varies across populations and is
      shaped by both environmental and genetic factors. Because the candidate gene
      vitamin K epoxide reductase complex subunit 1 (VKORC1) generates vitamin K
      quinone, a cofactor for the gamma-carboxylation of bone-related proteins such as
      osteocalcin, we hypothesized that VKORC1 genetic variants may be associated with
      BMD and osteoporosis in the general population. To test this hypothesis, we
      genotyped six VKORC1 SNPs in 7,159 individuals from the Third National Health and
      Nutrition Examination Survey (NHANES III). NHANES III is a nationally
      representative sample linked to health and lifestyle variables including BMD,
      which was measured using dual energy x-ray absorptiometry (DEXA) on four regions
      of the proximal femur. In adjusted models stratified by race/ethnicity and sex,
      SNPs rs9923231 and rs9934438 were associated with increased BMD (p=0.039 and
      0.024, respectively) while rs8050894 was associated with decreased BMD (p=0.016)
      among non-Hispanic black males (n=619). VKORC1 rs2884737 was associated with
      decreased BMD among Mexican-American males (n=795; p=0.004). We then tested for
      associations between VKORC1 SNPs and osteoporosis, but the results did not mirror
      the associations observed between VKORC1 and BMD, possibly due to small numbers
      of cases. This is the first report of VKORC1 common genetic variation associated
      with BMD, and one of the few reports available that investigate the genetics of
      BMD and osteoporosis in diverse populations.

PMID- 21179440
TI  - Genetic history of hepatitis C virus in Venezuela: high diversity and long time
      of evolution of HCV genotype 2.
AB  - BACKGROUND: The subtype diversity of the hepatitis C virus (HCV) genotypes is
      unknown in Venezuela. METHODOLOGY/PRINCIPAL FINDINGS: Partial sequencing of the
      NS5B region was performed in 310 isolates circulating in patients from 1995 to
      2007. In the samples collected between 2005 and 2007, HCV genotype 1 (G1) was the
      most common genotype (63%), composed as expected of mainly G1a and G1b. G2 was
      the second most common genotype (33%), being G2a almost absent and G2j the most
      frequent subtype. Sequence analysis of the core region confirmed the subtype
      assignment performed within the NS5b region in 63 isolates. The complete genome
      sequence of G2j was obtained. G2j has been described in France, Canada and
      Burkina Fasso, but it was not found in Martinique, where several subtypes of G2
      circulate in the general population. Bayesian coalescence analysis indicated a
      most recent common ancestor (MRCA) of G2j around 1785, before the introduction of
      G1b (1869) and G1a (1922). While HCV G1a and G1b experienced a growth reduction
      since 1990, coincident with the time when blood testing was implemented in
      Venezuela, HCV G2j did not seem to reach growth equilibrium during this period.
      CONCLUSIONS/SIGNIFICANCE: Assuming the introduction of G2j from Africa during the
      slave trade, the high frequency of G2j found in Venezuela could suggest: 1- the
      introduction of African ethnic groups different from the ones introduced to
      Martinique or 2- the occurrence of a founder effect. This study represents an in
      depth analysis of the subtype diversity of HCV in Venezuela, which is still
      unexplored in the Americas and deserves further studies.

PMID- 21179441
TI  - Effects of an alpha-4 integrin inhibitor on restenosis in a new porcine model
      combining endothelial denudation and stent placement.
AB  - Restenosis remains the main complication of balloon angioplasty and/or stent
      implantation. Preclinical testing of new pharmacologic agents preventing
      restenosis largely rely on porcine models, where restenosis is assessed after
      endothelial abrasion of the arterial wall or stent implantation. We combined
      endothelial cell denudation and implantation of stents to develop a new
      clinically relevant porcine model of restenosis, and used this model to determine
      the effects of an alpha4 integrin inhibitor, ELN 457946, on restenosis. Balloon
      angioplasty endothelial cell denudation and subsequent implantation of bare metal
      stents in the left anterior descending coronary, iliac, and left common carotid
      arteries was performed in domestic pigs, treated with vehicle or ELN 457946, once
      weekly via subcutaneous injections, for four weeks. After 1 month, histopathology
      and morphometric analyses of the arteries showed complete healing and robust,
      consistent restenotic response in stented arteries. Treatment with ELN 457946
      resulted in a reduction in the neointimal response, with decreases in area
      percent stenosis between 12% in coronary arteries and 30% in peripheral vessels.
      This is the first description of a successful pig model combining endothelial
      cell denudation and bare metal stent implantation. This new double injury model
      may prove particularly useful to assess pharmacological effects of drug
      candidates on restenosis, in coronary and/or peripheral arteries. Furthermore,
      the ELN 457946 alpha4 integrin inhibitor, administered subcutaneously, reduced
      inflammation and restenosis in stented coronary and peripheral arteries in pigs,
      therefore representing a promising systemic therapeutic approach in reducing
      restenosis in patients undergoing angioplasty and/or stent implantation.

PMID- 21179442
TI  - MiR-886-3p down regulates CXCL12 (SDF1) expression in human marrow stromal cells.
AB  - Stromal Derived Factor 1 (SDF1 or CXCL12), is a chemokine known to be critical
      for the migration of cells in several tissue systems including the homing of the
      hematopoietic stem cell (HSC) to its niche in the bone marrow. A comparative
      analysis of miRNA expression profiles of two stromal cell lines, distinguishable
      by function and by CXCL12 expression (CXCL12+ and CXCL12-), revealed that the
      CXCL12- cells expressed>40 fold more miR-886-3p than the CXCL12+ cells. Screening
      studies showed that when miR-886-3p was transfected into the CXCL12+ stromal
      cells, the expression of CXCL12 was down-regulated by as much as 85% when
      compared to appropriate controls, and results in the loss of CXCL12-directed
      chemotaxis. Similar reductions in CXCL12 were obtained with the transfection of
      miR-886-3p into primary stromal cell cultures. Additional studies showed that miR
      886-3p specifically targeted the 3' untranslated region (UTR) of CXCL12 mRNA.
      These data suggest a role for miRNA in modulating the expression of CXCL12, a
      gene product with a critical role in hematopoietic regulation.

PMID- 21179443
TI  - Three novel downstream promoter elements regulate MHC class I promoter activity
      in mammalian cells.
AB  - BACKGROUND: MHC CLASS I TRANSCRIPTION IS REGULATED BY TWO DISTINCT TYPES OF
      REGULATORY PATHWAYS: 1) tissue-specific pathways that establish constitutive
      levels of expression within a given tissue and 2) dynamically modulated pathways
      that increase or decrease expression within that tissue in response to hormonal
      or cytokine mediated stimuli. These sets of pathways target distinct upstream
      regulatory elements, have distinct basal transcription factor requirements, and
      utilize discrete sets of transcription start sites within an extended core
      promoter. METHODOLOGY/PRINCIPAL FINDINGS: We studied regulatory elements within
      the MHC class I promoter by cellular transfection and in vitro transcription
      assays in HeLa, HeLa/CIITA, and tsBN462 of various promoter constructs. We have
      identified three novel MHC class I regulatory elements (GLE, DPE-L1 and DPE-L2),
      located downstream of the major transcription start sites, that contribute to the
      regulation of both constitutive and activated MHC class I expression. These
      elements located at the 3' end of the core promoter preferentially regulate the
      multiple transcription start sites clustered at the 5' end of the core promoter.
      CONCLUSIONS/SIGNIFICANCE: Three novel downstream elements (GLE, DPE-L1, DPE-L2),
      located between +1 and +32 bp, regulate both constitutive and activated MHC class
      I gene expression by selectively increasing usage of transcription start sites
      clustered at the 5' end of the core promoter upstream of +1 bp. Results indicate
      that the downstream elements preferentially regulate TAF1-dependent, relative to
      TAF1-independent, transcription.

PMID- 21179444
TI  - Regulation of granulocyte and macrophage populations of murine bone marrow cells
      by G-CSF and CD137 protein.
AB  - BACKGROUND: Granulocytes and monocytes/macrophages differentiate from common
      myeloid progenitor cells. Granulocyte colony-stimulating factor (G-CSF) and CD137
      (4-1BB, TNFRSF9) are growth and differentiation factors that induce granulocyte
      and macrophage survival and differentiation, respectively. This study describes
      the influence of G-CSF and recombinant CD137-Fc protein on myelopoiesis.
      METHODOLOGY/PRINCIPAL FINDINGS: Both, G-CSF and CD137 protein support
      proliferation and survival of murine bone marrow cells. G-CSF enhances
      granulocyte numbers while CD137 protein enhances macrophage numbers. Both growth
      factors together give rise to more cells than each factor alone. Titration of G
      CSF and CD137 protein dose-dependently changes the granulocyte/macrophage ratio
      in bone marrow cells. Both factors individually induce proliferation of
      hematopoietic progenitor cells (lin-, c-kit+) and differentiation to granulocytes
      and macrophages, respectively. The combination of G-CSF and CD137 protein further
      increases proliferation, and results in a higher number of macrophages than CD137
      protein alone, and a lower number of granulocytes than G-CSF alone demonstrating
      that CD137 protein-induced monocytic differentiation is dominant over G-CSF
      induced granulocytic differentiation. CD137 protein induces monocytic
      differentiation even in early hematopoietic progenitor cells, the common myeloid
      progenitors and the granulocyte macrophage progenitors. CONCLUSIONS/SIGNIFICANCE:
      This study confirms earlier data on the regulation of myelopoiesis by CD137
      receptor - ligand interaction, and extends them by demonstrating the restriction
      of this growth promoting influence to the monocytic lineage.

PMID- 21179445
TI  - Surface phenotype and functionality of WNV specific T cells differ with age and
      disease severity.
AB  - West Nile virus (WNV) infection can result in severe neuroinvasive disease,
      particularly in persons with advanced age. As rodent models demonstrate that T
      cells play an important role in limiting WNV infection, and strong T cell
      responses to WNV have been observed in humans, we postulated that inadequate
      antiviral T cell immunity was involved in neurologic sequelae and the more severe
      outcomes associated with age. We previously reported the discovery of six HLA
      A*0201 restricted WNV peptide epitopes, with the dominant T cell targets in
      naturally infected individuals being SVG9 (Env) and SLF9 (NS4b). Here, memory
      phenotype and polyfunctional CD8+ T cell responses to these dominant epitopes
      were assessed in 40 WNV seropositive patients displaying diverse clinical
      symptoms. The patients' PBMC were stained with HLA-I multimers loaded with the
      SVG9 and SLF9 epitopes and analyzed by multicolor flow cytometry. WNV-specific
      CD8+ T cells were found in peripheral blood several months post infection. The
      number of WNV-specific T cells in older individuals was the same, if not greater,
      than in younger members of the cohort. WNV-specific T cells were predominantly
      monofunctional for CD107a, MIP-1beta, TNFalpha, IL-2, or IFNgamma. When CD8+ T
      cell responses were stratified by disease severity, an increased number of
      terminally differentiated, memory phenotype (CD45RA+ CD27- CCR7- CD57+) T cells
      were detected in patients suffering from viral neuroinvasion. In conclusion, T
      cells of a terminally differentiated/cytolytic profile are associated with
      neuroinvasion and, regardless of age, monofunctional T cells persist following
      infection. These data provide the first indication that particular CD8+ T cell
      phenotypes are associated with disease outcome following WNV infection.

PMID- 21179446
TI  - Trans-cellular introduction of HIV-1 protein Nef induces pathogenic response in
      Caenorhabditis elegans.
AB  - BACKGROUND: Caenorhabditis elegans has emerged as a very powerful model for
      studying the host pathogen interactions. Despite the absence of a naturally
      occurring viral infection for C. elegans, the model is now being exploited
      experimentally to study the basic aspects of virus-host interplay. The data
      generated from recent studies suggests that the virus that infects mammalian
      cells does infect, replicate and accumulate in C. elegans. METHODOLOGY/PRINCIPAL
      FINDINGS: We took advantage of the easy-to-achieve protein introduction in C.
      elegans and employing the methodology, we administered HIV-1 protein Nef into
      live worms. Nef is known to be an important protein for exacerbating HIV-1
      pathogenesis in host by enhancing viral replication. The deletion of nef from the
      viral genome has been reported to inhibit its replication in the host, thereby
      leading to delayed pathogenesis. Our studies, employing Nef introduction into C.
      elegans, led to creation of an in-vivo model that allowed us to study, whether or
      not, the protein induces effect in the whole organism. We observed a marked
      lipodystrophy, effect on neuromuscular function, impaired fertility and reduced
      longevity in the worms exposed to Nef. The observed effects resemble to those
      observed in Nef transgenic mice and most interestingly the effects also relate to
      some of the pathogenic aspects exhibited by human AIDS patients.
      CONCLUSIONS/SIGNIFICANCE: Our studies underline the importance of this in vivo
      model for studying the interactions of Nef with host proteins, which could
      further be used for identifying possible inhibitors of such interactions.

PMID- 21179447
TI  - Methamphetamine-induced dopamine-independent alterations in striatal gene
      expression in the 6-hydroxydopamine hemiparkinsonian rats.
AB  - Unilateral injections of 6-hydroxydopamine into the medial forebrain bundle are
      used extensively as a model of Parkinson's disease. The present experiments
      sought to identify genes that were affected in the dopamine (DA)-denervated
      striatum after 6-hydroxydopamine-induced destruction of the nigrostriatal
      dopaminergic pathway in the rat. We also examined whether a single injection of
      methamphetamine (METH) (2.5 mg/kg) known to cause changes in gene expression in
      the normally DA-innervated striatum could still influence striatal gene
      expression in the absence of DA. Unilateral injections of 6-hydroxydopamine into
      the medial forebrain bundle resulted in METH-induced rotational behaviors
      ipsilateral to the lesioned side and total striatal DA depletion on the lesioned
      side. This injection also caused decrease in striatal serotonin (5-HT) and 5
      hydroxyindoleacetic acid (5-HIAA) levels. DA depletion was associated with
      increases in 5-HIAA/5-HT ratios that were potentiated by the METH injection.
      Microarray analyses revealed changes (+/-1.7-fold, p<0.025) in the expression of
      67 genes on the lesioned side in comparison to the intact side of the saline
      treated hemiparkinsonian animals. These include follistatin, neuromedin U, and
      tachykinin 2 which were up-regulated. METH administration caused increases in the
      expression of c-fos, Egr1, and Nor-1 on the intact side. On the DA-depleted side,
      METH administration also increased the expression of 61 genes including Pdgf-d
      and Cox-2. There were METH-induced changes in 16 genes that were common in the DA
      innervated and DA-depleted sides. These include c-fos and Nor-1 which show
      greater changes on the normal DA side. Thus, the present study documents, for the
      first time, that METH mediated DA-independent changes in the levels of
      transcripts of several genes in the DA-denervated striatum. Our results also
      implicate 5-HT as a potential player in these METH-induced alterations in gene
      expression because the METH injection also caused significant increases in 5
      HIAA/5-HT ratios on the DA-depleted side.

PMID- 21179448
TI  - Factors associated with self and informant ratings of the quality of life of
      people with dementia living in care facilities: a cross sectional study.
AB  - BACKGROUND: There is no consensus regarding the optimal approach to assessment of
      the quality of life of people with dementia. We undertook the present study to
      describe and determine the factors associated with ratings of the quality of life
      of a cohort of people with dementia living in a residential care facility.
      METHODOLOGY/PRINCIPAL FINDINGS: 351 people with dementia living in residential
      care facilities, and their staff and family informants participated in this cross
      sectional observational study. Quality of life was measured using self (Quality
      of Life in Alzheimer's Disease [QoL-AD] scale), and informant (QoL-AD and
      Alzheimer's Disease Related QoL Scale) reports. 226 people (64%) with dementia
      (median MMSE 17; 12-21) were able to self rate the QoL-AD scale and these
      subjects' ratings were compared to ratings by staff and family. Both staff and
      family informant ratings of the QoL-AD underestimated self ratings (mean
      difference -7.8, 95% CI -8.8, -6.7 for staff rated QoL-AD; and mean difference 
      7.2, 95% CI -8.5, -6.0 for family rated QoL-AD). Self ratings of QoL were lower
      among people who were restrained, had fallen or had pain. Informant ratings of
      the QoL of the participants with dementia were consistently and significantly
      lower for people with severe cognitive impairment, who had fallen, had presence
      of neuropsychiatric symptoms, or where care giver distress was present.
      Documented restraint, reported pain and neuropsychiatric symptoms were
      independently associated with lower self rating of the QoL-AD in multivariate
      models. Cognitive impairment, case conferencing, hospitalizations and
      neuropsychiatric symptoms were found to be independently associated with staff
      rated ADRQL. CONCLUSIONS: The majority of people with dementia living in
      residential care facilities can rate their own QoL. Informant ratings
      underestimate self ratings of QoL of people with dementia, and appear to be
      associated with factors which are not associated with self ratings.

PMID- 21179449
TI  - Soft substrates promote homogeneous self-renewal of embryonic stem cells via
      downregulating cell-matrix tractions.
AB  - Maintaining undifferentiated mouse embryonic stem cell (mESC) culture has been a
      major challenge as mESCs cultured in Leukemia Inhibitory Factor (LIF) conditions
      exhibit spontaneous differentiation, fluctuating expression of pluripotency
      genes, and genes of specialized cells. Here we show that, in sharp contrast to
      the mESCs seeded on the conventional rigid substrates, the mESCs cultured on the
      soft substrates that match the intrinsic stiffness of the mESCs and in the
      absence of exogenous LIF for 5 days, surprisingly still generated homogeneous
      undifferentiated colonies, maintained high levels of Oct3/4, Nanog, and Alkaline
      Phosphatase (AP) activities, and formed embryoid bodies and teratomas
      efficiently. A different line of mESCs, cultured on the soft substrates without
      exogenous LIF, maintained the capacity of generating homogeneous undifferentiated
      colonies with relatively high levels of Oct3/4 and AP activities, up to at least
      15 passages, suggesting that this soft substrate approach applies to long term
      culture of different mESC lines. mESC colonies on these soft substrates without
      LIF generated low cell-matrix tractions and low stiffness. Both tractions and
      stiffness of the colonies increased with substrate stiffness, accompanied by
      downregulation of Oct3/4 expression. Our findings demonstrate that mESC self
      renewal and pluripotency can be maintained homogeneously on soft substrates via
      the biophysical mechanism of facilitating generation of low cell-matrix
      tractions.

PMID- 21179450
TI  - Environmental and lifestyle factors associated with perceived facial age in
      Chinese women.
AB  - Perceived facial age has been proposed as a biomarker of ageing with 'looking
      young for one's age' linked to physical and cognitive functioning and to
      increased survival for Caucasians. We have investigated the environmental and
      lifestyle factors associated with perceived facial ageing in Chinese women.
      Facial photographs were collected from 250 Chinese women, aged 25-70 years in
      Shanghai, China. Perceived facial age was determined and related to chronological
      age for each participant. Lifestyle and health information was collected by
      questionnaire. Bivariate analyses (controlling for chronological age) identified
      and quantified lifestyle variables associated with perceived facial age.
      Independent predictors of perceived age were identified by multivariate
      modelling. Factors which significantly associated with looking younger for one's
      chronological age included greater years of education (p<0.001), fewer household
      members (p=0.027), menopausal status (p=0.020), frequency of visiting one's
      doctor (p=0.013), working indoors (p<0.001), spending less time in the sun
      (p=0.015), moderate levels of physical activity (p=0.004), higher frequency of
      teeth cleaning (p<0.001) and more frequent use of facial care products: cleanser
      (p<0.001); moisturiser (p=0.016) or night cream (p=0.016). Overall, 36.5% of the
      variation in the difference between perceived and chronological age could be
      explained by a combination of chronological age and 6 independent lifestyle
      variables. We have thus identified and quantified a number of factors associated
      with younger appearance in Chinese women. Presentation of these factors in the
      context of facial appearance could provide significant motivation for the
      adoption of a range of healthy behaviours at the level of both individuals and
      populations.

PMID- 21179451
TI  - Galanin receptor 1 deletion exacerbates hippocampal neuronal loss after systemic
      kainate administration in mice.
AB  - BACKGROUND: Galanin is a neuropeptide with a wide distribution in the central and
      peripheral nervous systems and whose physiological effects are mediated through
      three G protein-coupled receptor subtypes, GalR1, GalR2, and GalR3. Several lines
      of evidence indicate that galanin, as well as activation of the GalR1 receptor,
      is a potent and effective modulator of neuronal excitability in the hippocampus.
      METHODOLOGY/PRINCIPAL FINDINGS: In order to test more formally the potential
      influence of GalR1 on seizure-induced excitotoxic cell death, we conducted
      functional complementation tests in which transgenic mice that exhibit decreased
      expression of the GalR1 candidate mRNA underwent kainate-induced status
      epilepticus to determine if the quantitative trait of susceptibility to seizure
      induced cell death is determined by the activity of GalR1. In the present study,
      we report that reduction of GalR1 mRNA via null mutation or injection of the
      GalR1 antagonist, galantide, prior to kainate-induced status epilepticus induces
      hippocampal damage in a mouse strain known to be highly resistant to kainate
      induced neuronal injury. Wild-type and GalR1 knockout mice were subjected to
      systemic kainate administration. Seven days later, Nissl and NeuN immune-
      staining demonstrated that hippocampal cell death was significantly increased in
      GalR1 knockout strains and in animals injected with the GalR1 antagonist.
      Compared to GalR1-expressing mice, GalR1-deficient mice had significantly larger
      hippocampal lesions after status epilepticus. CONCLUSIONS/SIGNIFICANCE: Our
      results suggest that a reduction of GalR1 expression in the C57BL/6J mouse strain
      renders them susceptible to excitotoxic injury following systemic kainate
      administration. From these results, GalR1 protein emerges as a new molecular
      target that may have a potential therapeutic value in modulating seizure-induced
      cell death.

PMID- 21179452
TI  - Maternal undernutrition significantly impacts ovarian follicle number and
      increases ovarian oxidative stress in adult rat offspring.
AB  - BACKGROUND: We have shown recently that maternal undernutrition (UN) advanced
      female pubertal onset in a manner that is dependent upon the timing of UN. The
      long-term consequence of this accelerated puberty on ovarian function is unknown.
      Recent findings suggest that oxidative stress may be one mechanism whereby early
      life events impact on later physiological functioning. Therefore, using an
      established rodent model of maternal UN at critical windows of development, we
      examined maternal UN-induced changes in offspring ovarian function and determined
      whether these changes were underpinned by ovarian oxidative stress.
      METHODOLOGY/PRINCIPAL FINDINGS: Our study is the first to show that maternal UN
      significantly reduced primordial and secondary follicle number in offspring in a
      manner that was dependent upon the timing of maternal UN. Specifically, a
      reduction in these early stage follicles was observed in offspring born to
      mothers undernourished throughout both pregnancy and lactation. Additionally,
      antral follicle number was reduced in offspring born to all mothers that were UN
      regardless of whether the period of UN was restricted to pregnancy or lactation
      or both. These reductions were associated with decreased mRNA levels of genes
      critical for follicle maturation and ovulation. Increased ovarian protein
      carbonyls were observed in offspring born to mothers UN during pregnancy and/or
      lactation and this was associated with peroxiredoxin 3 hyperoxidation and reduced
      mRNA levels; suggesting compromised antioxidant defence. This was not observed in
      offspring of mothers UN during lactation alone. CONCLUSIONS: We propose that
      maternal UN, particularly at a time-point that includes pregnancy, results in
      reduced offspring ovarian follicle numbers and mRNA levels of regulatory genes
      and may be mediated by increased ovarian oxidative stress coupled with a
      decreased ability to repair the resultant oxidative damage. Together these data
      are suggestive of maternal UN potentially contributing to premature ovarian
      ageing in offspring.

PMID- 21179453
TI  - TogoDoc server/client system: smart recommendation and efficient management of
      life science literature.
AB  - In this paper, we describe a server/client literature management system
      specialized for the life science domain, the TogoDoc system (Togo, pronounced Toe
      Go, is a romanization of a Japanese word for integration). The server and the
      client program cooperate closely over the Internet to provide life scientists
      with an effective literature recommendation service and efficient literature
      management. The content-based and personalized literature recommendation helps
      researchers to isolate interesting papers from the "tsunami" of literature, in
      which, on average, more than one biomedical paper is added to MEDLINE every
      minute. Because researchers these days need to cover updates of much wider topics
      to generate hypotheses using massive datasets obtained from public databases or
      omics experiments, the importance of having an effective literature
      recommendation service is rising. The automatic recommendation is based on the
      content of personal literature libraries of electronic PDF papers. The client
      program automatically analyzes these files, which are sometimes deeply buried in
      storage disks of researchers' personal computers. Just saving PDF papers to the
      designated folders makes the client program automatically analyze and retrieve
      metadata, rename file names, synchronize the data to the server, and receive the
      recommendation lists of newly published papers, thus accomplishing effortless
      literature management. In addition, the tag suggestion and associative search
      functions are provided for easy classification of and access to past papers
      (researchers who read many papers sometimes only vaguely remember or completely
      forget what they read in the past). The TogoDoc system is available for both
      Windows and Mac OS X and is free. The TogoDoc Client software is available at
      http://tdc.cb.k.u-tokyo.ac.jp/, and the TogoDoc server is available at
      https://docman.dbcls.jp/pubmed_recom.

PMID- 21179454
TI  - Comprehensive gene-expression survey identifies wif1 as a modulator of
      cardiomyocyte differentiation.
AB  - During chicken cardiac development the proepicardium (PE) forms the epicardium
      (Epi), which contributes to several non-myocardial lineages within the heart. In
      contrast to Epi-explant cultures, PE explants can differentiate into a
      cardiomyocyte phenotype. By temporal microarray expression profiles of PE-explant
      cultures and maturing Epi cells, we identified genes specifically associated with
      differentiation towards either of these lineages and genes that are associated
      with the Epi-lineage restriction. We found a central role for Wnt signaling in
      the determination of the different cell lineages. Immunofluorescent staining
      after recombinant-protein incubation in PE-explant cultures indicated that the
      early upregulated Wnt inhibitory factor-1 (Wif1), stimulates cardiomyocyte
      differentiation in a similar manner as Wnt stimulation. Concordingly, in the
      mouse pluripotent embryogenic carcinoma cell line p19cl6, early and late Wif1
      exposure enhances and attenuates differentiation, respectively. In ovo exposure
      of the HH12 chicken embryonic heart to Wif1 increases the Tbx18-positive cardiac
      progenitor pool. These data indicate that Wif1 enhances cardiomyogenesis.

PMID- 21179455
TI  - The neurotoxicity of DOPAL: behavioral and stereological evidence for its role in
      Parkinson disease pathogenesis.
AB  - BACKGROUND: The etiology of Parkinson disease (PD) has yet to be fully
      elucidated. We examined the consequences of injections of 3,4
      dihydroxyphenylacetaldehyde (DOPAL), a toxic metabolite of dopamine, into the
      substantia nigra of rats on motor behavior and neuronal survival.
      METHODS/PRINCIPAL FINDINGS: A total of 800 nl/rat of DOPAL (1 ug/200 nl) was
      injected stereotaxically into the substantia nigra over three sites while control
      animals received similar injections of phosphate buffered saline. Rotational
      behavior of these rats was analyzed, optical density of striatal tyrosine
      hydroxylase was calculated, and unbiased stereological counts of the substantia
      nigra were made. The rats showed significant rotational asymmetry ipsilateral to
      the lesion, supporting disruption of dopaminergic nigrostriatal projections. Such
      disruption was verified since the density of striatal tyrosine hydroxylase
      decreased significantly (p<0.001) on the side ipsilateral to the DOPAL injections
      when compared to the non-injected side. Stereological counts of neurons stained
      for Nissl in pars compacta of the substantia nigra significantly decreased
      (p<0.001) from control values, while counts of those in pars reticulata were
      unchanged after DOPAL injections. Counts of neurons immunostained for tyrosine
      hydroxylase also showed a significant (p=0.032) loss of dopaminergic neurons. In
      spite of significant loss of dopaminergic neurons, DOPAL injections did not
      induce significant glial reaction in the substantia nigra. CONCLUSIONS: The
      present study provides the first in vivo quantification of substantia nigra pars
      compacta neuronal loss after injection of the endogenous toxin DOPAL. The results
      demonstrate that injections of DOPAL selectively kills SN DA neurons, suggests
      loss of striatal DA terminals, spares non-dopaminergic neurons of the pars
      reticulata, and triggers a behavioral phenotype (rotational asymmetry) consistent
      with other PD animal models. This study supports the "catecholaldehyde
      hypothesis" as an important link for the etiology of sporadic PD.

PMID- 21179456
TI  - Vaccinia-related kinase 1 is required for the maintenance of undifferentiated
      spermatogonia in mouse male germ cells.
AB  - Vaccinia-related kinase 1 (VRK1) is a crucial protein kinase for mitotic
      regulation. VRK1 is known to play a role in germ cell development, and its
      deficiency results in sterility. Here we describe that VRK1 is essential for the
      maintenance of spermatogonial stem cells. To determine whether VRK1 plays a role
      in these cells, we assessed the population size of undifferentiated
      spermatogonia. Flow cytometry analyses showed that the number of undifferentiated
      spermatogonia was markedly reduced in VRK1-deficient testes. VRK1 was highly
      expressed in spermatogonial populations, and approximately 66% of
      undifferentiated spermatogonia that were sorted as an Ep-CAM+/c-kit-/alpha-6
      integrin+ population showed a positive signal for VRK1. Undifferentiated stem
      cells expressing Plzf and Oct4 but not c-kit also expressed VRK1, suggesting that
      VRK1 is an intrinsic factor for the maintenance of spermatogonial stem cells.
      Microarray analyses of the global testicular transcriptome and quantitative RT
      PCR of VRK1-deficient testes revealed significantly reduced expression levels of
      undifferentiated spermatogonial marker genes in early postnatal mice. Together,
      these results suggest that VRK1 is required for the proliferation and
      differentiation of undifferentiated spermatogonia, which are essential for
      spermatogenic cell maintenance.

PMID- 21179457
TI  - An improved chamber for direct visualisation of chemotaxis.
AB  - There has been a growing appreciation over the last decade that chemotaxis plays
      an important role in cancer migration, invasion and metastasis. Research into the
      field of cancer cell chemotaxis is still in its infancy and traditional
      investigative tools have been developed with other cell types and purposes in
      mind. Direct visualisation chambers are considered the gold standard for
      investigating the behaviour of cells migrating in a chemotactic gradient. We
      therefore drew up a list of key attributes that a chemotaxis chamber should have
      for investigating cancer cell chemotaxis. These include (1) compatibility with
      thin cover slips for optimal optical properties and to allow use of high
      numerical aperture (NA) oil immersion objectives; (2) gradients that are
      relatively stable for at least 24 hours due to the slow migration of cancer
      cells; (3) gradients of different steepnesses in a single experiment, with
      defined, consistent directions to avoid the need for complicated analysis; and
      (4) simple handling and disposability for use with medical samples. Here we
      describe and characterise the Insall chamber, a novel direct visualisation
      chamber. We use it to show GFP-lifeact transfected MV3 melanoma cells chemotaxing
      using a 60x high NA oil immersion objective, which cannot usually be done with
      other chemotaxis chambers. Linear gradients gave very efficient chemotaxis,
      contradicting earlier results suggesting that only polynomial gradients were
      effective. In conclusion, the chamber satisfies our design criteria, most
      importantly allowing high NA oil immersion microscopy to track chemotaxing cancer
      cells in detail over 24 hours.

PMID- 21179458
TI  - Resveratrol induces growth arrest and apoptosis through activation of FOXO
      transcription factors in prostate cancer cells.
AB  - BACKGROUND: Resveratrol, a naturally occurring phytopolyphenol compound, has
      attracted extensive interest in recent years because of its diverse
      pharmacological characteristics. Although resveratrol possesses chemopreventive
      properties against several cancers, the molecular mechanisms by which it inhibits
      cell growth and induces apoptosis have not been clearly understood. The present
      study was carried out to examine whether PI3K/AKT/FOXO pathway mediates the
      biological effects of resveratrol. METHODOLOGY/PRINCIPAL FINDINGS: Resveratrol
      inhibited the phosphorylation of PI3K, AKT and mTOR. Resveratrol, PI3K inhibitors
      (LY294002 and Wortmannin) and AKT inhibitor alone slightly induced apoptosis in
      LNCaP cells. These inhibitors further enhanced the apoptosis-inducing potential
      of resveratrol. Overexpression of wild-type PTEN slightly induced apoptosis. Wild
      type PTEN and PTEN-G129E enhanced resveratrol-induced apoptosis, whereas PTEN
      G129R had no effect on proapoptotic effects of resveratrol. Furthermore,
      apoptosis-inducing potential of resveratrol was enhanced by dominant negative
      AKT, and inhibited by wild-type AKT and constitutively active AKT. Resveratrol
      has no effect on the expression of FKHR, FKHRL1 and AFX genes. The inhibition of
      FOXO phosphorylation by resveratrol resulted in its nuclear translocation, DNA
      binding and transcriptional activity. The inhibition of PI3K/AKT pathway induced
      FOXO transcriptional activity resulting in induction of Bim, TRAIL, p27/KIP1, DR4
      and DR5, and inhibition of cyclin D1. Similarly, resveratrol-induced FOXO
      transcriptional activity was further enhanced when activation of PI3K/AKT pathway
      was blocked. Over-expression of phosphorylation deficient mutants of FOXO
      proteins (FOXO1-TM, FOXO3A-TM and FOXO4-TM) induced FOXO transcriptional
      activity, which was further enhanced by resveratrol. Inhibition of FOXO
      transcription factors by shRNA blocked resveratrol-induced upregulation of Bim,
      TRAIL, DR4, DR5, p27/KIP1 and apoptosis, and inhibition of cyclin D1 by
      resveratrol. CONCLUSION/SIGNIFICANCE: These data suggest that FOXO transcription
      factors mediate anti-proliferative and pro-apoptotic effects of resveratrol, in
      part due to activation of extrinsic apoptosis pathway.

PMID- 21179459
TI  - A reliability-generalization study of journal peer reviews: a multilevel meta
      analysis of inter-rater reliability and its determinants.
AB  - BACKGROUND: This paper presents the first meta-analysis for the inter-rater
      reliability (IRR) of journal peer reviews. IRR is defined as the extent to which
      two or more independent reviews of the same scientific document agree.
      METHODOLOGY/PRINCIPAL FINDINGS: Altogether, 70 reliability coefficients (Cohen's
      Kappa, intra-class correlation [ICC], and Pearson product-moment correlation [r])
      from 48 studies were taken into account in the meta-analysis. The studies were
      based on a total of 19,443 manuscripts; on average, each study had a sample size
      of 311 manuscripts (minimum: 28, maximum: 1983). The results of the meta-analysis
      confirmed the findings of the narrative literature reviews published to date: The
      level of IRR (mean ICC/r2=.34, mean Cohen's Kappa=.17) was low. To explain the
      study-to-study variation of the IRR coefficients, meta-regression analyses were
      calculated using seven covariates. Two covariates that emerged in the meta
      regression analyses as statistically significant to gain an approximate
      homogeneity of the intra-class correlations indicated that, firstly, the more
      manuscripts that a study is based on, the smaller the reported IRR coefficients
      are. Secondly, if the information of the rating system for reviewers was reported
      in a study, then this was associated with a smaller IRR coefficient than if the
      information was not conveyed. CONCLUSIONS/SIGNIFICANCE: Studies that report a
      high level of IRR are to be considered less credible than those with a low level
      of IRR. According to our meta-analysis the IRR of peer assessments is quite
      limited and needs improvement (e.g., reader system).

PMID- 21179460
TI  - Shift work is not associated with high blood pressure or prevalence of
      hypertension.
AB  - BACKGROUND: Working mostly at night has been suggested to be associated with
      upset of chronobiological rhythms and high blood pressure, but the evidence from
      epidemiological studies is weak. METHODS: In a cross-sectional survey, we
      evaluated the association between shift work and blood pressure, pre-hypertension
      and hypertension. In total, 493 nurses, nurse technicians and assistants, were
      selected at random in a large general hospital setting. Hypertension was
      diagnosed by the mean of four automatic blood pressure readings>=140/90 mmHg or
      use of blood pressure lowering agents, and pre-hypertension by systolic blood
      pressure>=120-139 or diastolic blood pressure>=80-89 mmHg. Risk factors for
      hypertension were evaluated by a standardized questionnaire and anthropometric
      measurements. The association between the shift of work and blood pressure, pre
      hypertension and hypertension was explored using univariate and multivariate
      analyses that controlled for risk factors for hypertension by covariance analysis
      and modified Poisson regression. RESULTS: The mean age of the participants was
      34.3+/-9.4 years and 88.2% were women. Night shift workers were older, more
      frequently married or divorced, and less educated. The prevalence of hypertension
      in the whole sample was 16%, and 28% had pre-hypertension. Blood pressure (after
      adjustment for confounding) was not different in day and night shift workers. The
      prevalence of hypertension and pre-hypertension by shift work was not different
      in the univariate analysis and after adjustment for confounding (all risk
      ratios=1.0). CONCLUSION: Night shift work did not increase blood pressure and was
      not associated with hypertension or pre-hypertension in nursing personnel working
      in a large general hospital.

PMID- 21179461
TI  - Physician attitudes towards pharmacological cognitive enhancement: safety
      concerns are paramount.
AB  - The ethical dimensions of pharmacological cognitive enhancement have been widely
      discussed in academic circles and the popular media, but missing from the
      conversation have been the perspectives of physicians - key decision makers in
      the adoption of new technologies into medical practice. We queried primary care
      physicians in major urban centers in Canada and the United States with the aim of
      understanding their attitudes towards cognitive enhancement. Our primary
      hypothesis was that physicians would be more comfortable prescribing cognitive
      enhancers to older patients than to young adults. Physicians were presented with
      a hypothetical pharmaceutical cognitive enhancer that had been approved by the
      regulatory authorities for use in healthy adults, and was characterized as being
      safe, effective, and without significant adverse side effects. Respondents
      overwhelmingly reported increasing comfort with prescribing cognitive enhancers
      as the patient age increased from 25 to 65. When asked about their comfort with
      prescribing extant drugs that might be considered enhancements (sildenafil,
      modafinil, and methylphenidate) or our hypothetical cognitive enhancer to a
      normal, healthy 40 year old, physicians were more comfortable prescribing
      sildenafil than any of the other three agents. When queried as to the reasons
      they answered as they did, the most prominent concerns physicians expressed were
      issues of safety that were not offset by the benefit afforded the individual,
      even in the face of explicit safety claims. Moreover, many physicians indicated
      that they viewed safety claims with considerable skepticism. It has become
      routine for safety to be raised and summarily dismissed as an issue in the debate
      over pharmacological cognitive enhancement; the observation that physicians were
      so skeptical in the face of explicit safety claims suggests that such a
      conclusion may be premature. Thus, physician attitudes suggest that greater
      weight be placed upon the balance between safety and benefit in consideration of
      pharmacological cognitive enhancement.

PMID- 21179462
TI  - Evidence of simultaneous circulation of West Nile and Usutu viruses in mosquitoes
      sampled in Emilia-Romagna region (Italy) in 2009.
AB  - BACKGROUND: In recent years human diseases due to mosquito-borne viruses were
      increasingly reported in Emilia-Romagna region (Italy), from the chikungunya
      virus in 2007 to the West Nile virus (WNV) in 2008. An extensive entomological
      survey was performed in 2009 to establish the presence and distribution of
      mosquito arboviruses in this region, with particular reference to flaviviruses.
      METHODOLOGY/PRINCIPAL FINDINGS: From May 6 to October 31, a total of 190,516
      mosquitoes were sampled in georeferenced stations, grouped in 1,789 pools
      according date of collection, location, and species, and analyzed by reverse
      transcription polymerase chain reaction (RT-PCR) to detect the presence of RNA
      belong to Flavivirus genus. WNV was detected in 27 mosquito pools, producing
      sequences similar to those of birds and human strains obtained in 2008 outbreak,
      pointed out the probable virus overwintering. Isolation of WNV was achieved from
      one of these pools. Moreover 56 pools of mosquitoes tested positive for Usutu
      virus (USUV). Most PCR positive pools consisted of Culex pipiens, which also was
      the most analyzed mosquito species (81.4% of specimens); interestingly, USUV RNA
      was also found in two Aedes albopictus mosquito pools. Simultaneous circulation
      of WNV and USUV in the survey area was highlighted by occurrence of 8 mosquito
      WNV- and USUV-positive pools and by the overlaying of the viruses "hot spots",
      obtained by kernel density estimation (KDE) analysis. Land use of sampled
      stations pointed out a higher proportion of WNV-positive Cx. pipiens pool in
      rural environments respect the provenience of total sampled pool, while the USUV
      positive pools were uniformly captured in the different environments.
      CONCLUSIONS/SIGNIFICANCE: Obtained data highlighting the possible role of Cx.
      pipiens mosquito as the main vector for WNV and USUV in Northern Italy, and the
      possible involvement of Ae. albopictus mosquito in USUV cycle. The described
      mosquito-based surveillance could constitute the foundation for a public health
      alert system targeting mosquito borne arboviruses.

PMID- 21179463
TI  - Polyphosphate kinase from M. tuberculosis: an interconnect between the genetic
      and biochemical role.
AB  - The enzyme Polyphosphate Kinase (PPK) catalyses the reversible transfer of the
      terminal gamma-Pi of ATP to form a long chain Polyphosphate (PolyP). Using an
      IPTG inducible mycobacterial vector, the vulnerability of this gene has been
      evaluated by antisense knockdown experiments in M. tuberculosis. Expression
      profiling studies point to the fact that down regulation of PPK caused cidality
      during the late phase in contrast to its bacteriostatic mode immediately
      following antisense expression. PPK thus seems to be a suitable anti-tubercular
      drug target. The enzyme which is a tetramer has been cloned in E. coli and
      purified to homogeneity. An enzyme assay suitable for High Throughput Screening
      was optimized by using the statistical Taguchi protocol and the kinetic
      parameters determined. The enzyme displayed a strong product inhibition by ADP.
      In order to accurately estimate the product inhibition, progress curve analysis
      of the enzyme reaction was monitored. The kinetic equation describing the
      progress curve was suitably modified by taking into account the product
      inhibition. The reversible nature of the enzyme indicated a possibility of a two
      way ATP<->ADP switch operating in the bacteria as a response to its growth
      requirement.

PMID- 21179464
TI  - Neural correlates of behavioural olfactory sensitivity changes seasonally in
      European starlings.
AB  - BACKGROUND: Possibly due to the small size of the olfactory bulb (OB) as compared
      to rodents, it was generally believed that songbirds lack a well-developed sense
      of smell. This belief was recently revised by several studies showing that
      various bird species, including passerines, use olfaction in many respects of
      life. During courtship and nest building, male European starlings (Sturnus
      vulgaris) incorporate aromatic herbs that are rich in volatile compounds (e.g.,
      milfoil, Achillea millefolium) into the nests and they use olfactory cues to
      identify these plants. Interestingly, European starlings show seasonal
      differences in their ability to respond to odour cues: odour sensitivity peaks
      during nest-building in the spring, but is almost non-existent during the non
      breeding season. METHODOLOGY/PRINCIPAL FINDINGS: This study used repeated in vivo
      Manganese-enhanced MRI to quantify for the first time possible seasonal changes
      in the anatomy and activity of the OB in starling brains. We demonstrated that
      the OB of the starling exhibits a functional seasonal plasticity of certain plant
      odour specificity and that the OB is only able to detect milfoil odour during the
      breeding season. Volumetric analysis showed that this seasonal change in activity
      is not linked to a change in OB volume. By subsequently experimentally elevating
      testosterone (T) in half of the males during the non-breeding season we showed
      that the OB volume was increased compared to controls. CONCLUSIONS/SIGNIFICANCE:
      By investigating the neural substrate of seasonal olfactory sensitivity changes
      we show that the starlings' OB loses its ability during the non-breeding season
      to detect a natural odour of a plant preferred as green nest material by male
      starlings. We found that testosterone, applied during the non-breeding season,
      does not restore the discriminatory ability of the OB but has an influence on its
      size.

PMID- 21179465
TI  - Uterine epithelial cell regulation of DC-SIGN expression inhibits
      transmitted/founder HIV-1 trans infection by immature dendritic cells.
AB  - BACKGROUND: Sexual transmission accounts for the majority of HIV-1 infections. In
      over 75% of cases, infection is initiated by a single variant
      (transmitted/founder virus). However, the determinants of virus selection during
      transmission are unknown. Host cell-cell interactions in the mucosa may be
      critical in regulating susceptibility to infection. We hypothesized in this study
      that specific immune modulators secreted by uterine epithelial cells modulate
      susceptibility of dendritic cells (DC) to infection with HIV-1.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we report that uterine epithelial cell
      secretions (i.e. conditioned medium, CM) decreased DC-SIGN expression on immature
      dendritic cells via a transforming growth factor beta (TGF-beta) mechanism.
      Further, CM inhibited dendritic cell-mediated trans infection of HIV-1 expressing
      envelope proteins of prototypic reference. Similarly, CM inhibited trans
      infection of HIV-1 constructs expressing envelopes of transmitted/founder
      viruses, variants that are selected during sexual transmission. In contrast,
      whereas recombinant TGF- beta1 inhibited trans infection of prototypic reference
      HIV-1 by dendritic cells, TGF-beta1 had a minimal effect on trans infection of
      transmitted/founder variants irrespective of the reporter system used to measure
      trans infection. CONCLUSIONS/SIGNIFICANCE: Our results provide the first direct
      evidence for uterine epithelial cell regulation of dendritic cell transmission of
      infection with reference and transmitted/founder HIV-1 variants. These findings
      have immediate implications for designing strategies to prevent sexual
      transmission of HIV-1.

PMID- 21179466
TI  - Presenilin controls CBP levels in the adult Drosophila central nervous system.
AB  - BACKGROUND: Dominant mutations in both human Presenilin (Psn) genes have been
      correlated with the formation of amyloid plaques and development of familial
      early-onset Alzheimer's disease (AD). However, a definitive mechanism whereby
      plaque formation causes the pathology of familial and sporadic forms of AD has
      remained elusive. Recent discoveries of several substrates for Psn protease
      activity have sparked alternative hypotheses for the pathophysiology underlying
      AD. CBP (CREB-binding protein) is a haplo-insufficient transcriptional co
      activator with histone acetly-transferase (HAT) activity that has been proposed
      to be a downstream target of Psn signaling. Individuals with altered CBP have
      cognitive deficits that have been linked to several neurological disorders.
      METHODOLOGY/PRINCIPAL FINDINGS: Using a transgenic RNA-interference strategy to
      selectively silence CBP, Psn, and Notch in adult Drosophila, we provide evidence
      for the first time that Psn is required for normal CBP levels and for maintaining
      specific global acetylations at lysine 8 of histone 4 (H4K8ac) in the central
      nervous system (CNS). In addition, flies conditionally compromised for the adult
      expression of CBP display an altered geotaxis behavior that may reflect a
      neurological defect. CONCLUSIONS/SIGNIFICANCE: Our data support a model in which
      Psn regulates CBP levels in the adult fly brain in a manner that is independent
      of Notch signaling. Although we do not understand the molecular mechanism
      underlying the association between Psn and CBP, our results underscore the need
      to learn more about the basic relationship between Psn-regulated substrates and
      essential functions of the nervous system.

PMID- 21179467
TI  - Identification of genes and networks driving cardiovascular and metabolic
      phenotypes in a mouse F2 intercross.
AB  - To identify the genes and pathways that underlie cardiovascular and metabolic
      phenotypes we performed an integrated analysis of a mouse C57BL/6JxA/J F2 (B6AF2)
      cross by relating genome-wide gene expression data from adipose, kidney, and
      liver tissues to physiological endpoints measured in the population. We have
      identified a large number of trait QTLs including loci driving variation in
      cardiac function on chromosomes 2 and 6 and a hotspot for adiposity, energy
      metabolism, and glucose traits on chromosome 8. Integration of adipose gene
      expression data identified a core set of genes that drive the chromosome 8
      adiposity QTL. This chromosome 8 trans eQTL signature contains genes associated
      with mitochondrial function and oxidative phosphorylation and maps to a
      subnetwork with conserved function in humans that was previously implicated in
      human obesity. In addition, human eSNPs corresponding to orthologous genes from
      the signature show enrichment for association to type II diabetes in the DIAGRAM
      cohort, supporting the idea that the chromosome 8 locus perturbs a molecular
      network that in humans senses variations in DNA and in turn affects metabolic
      disease risk. We functionally validate predictions from this approach by
      demonstrating metabolic phenotypes in knockout mice for three genes from the
      trans eQTL signature, Akr1b8, Emr1, and Rgs2. In addition we show that the
      transcriptional signatures for knockout of two of these genes, Akr1b8 and Rgs2,
      map to the F2 network modules associated with the chromosome 8 trans eQTL
      signature and that these modules are in turn very significantly correlated with
      adiposity in the F2 population. Overall this study demonstrates how integrating
      gene expression data with QTL analysis in a network-based framework can aid in
      the elucidation of the molecular drivers of disease that can be translated from
      mice to humans.

PMID- 21179469
TI  - Altered chromosomal positioning, compaction, and gene expression with a lamin A/C
      gene mutation.
AB  - BACKGROUND: Lamins A and C, encoded by the LMNA gene, are filamentous proteins
      that form the core scaffold of the nuclear lamina. Dominant LMNA gene mutations
      cause multiple human diseases including cardiac and skeletal myopathies. The
      nuclear lamina is thought to regulate gene expression by its direct interaction
      with chromatin. LMNA gene mutations may mediate disease by disrupting normal gene
      expression. METHODS/FINDINGS: To investigate the hypothesis that mutant lamin A/C
      changes the lamina's ability to interact with chromatin, we studied gene
      misexpression resulting from the cardiomyopathic LMNA E161K mutation and
      correlated this with changes in chromosome positioning. We identified clusters of
      misexpressed genes and examined the nuclear positioning of two such genomic
      clusters, each harboring genes relevant to striated muscle disease including LMO7
      and MBNL2. Both gene clusters were found to be more centrally positioned in LMNA
      mutant nuclei. Additionally, these loci were less compacted. In LMNA mutant heart
      and fibroblasts, we found that chromosome 13 had a disproportionately high
      fraction of misexpressed genes. Using three-dimensional fluorescence in situ
      hybridization we found that the entire territory of chromosome 13 was displaced
      towards the center of the nucleus in LMNA mutant fibroblasts. Additional
      cardiomyopathic LMNA gene mutations were also shown to have abnormal positioning
      of chromosome 13, although in the opposite direction. CONCLUSIONS: These data
      support a model in which LMNA mutations perturb the intranuclear positioning and
      compaction of chromosomal domains and provide a mechanism by which gene
      expression may be altered.

PMID- 21179468
TI  - Transcriptional activation of REST by Sp1 in Huntington's disease models.
AB  - In Huntington's disease (HD), mutant huntingtin (mHtt) disrupts the normal
      transcriptional program of disease neurons by altering the function of several
      gene expression regulators such as Sp1. REST (Repressor Element-1 Silencing
      Transcription Factor), a key regulator of neuronal differentiation, is also
      aberrantly activated in HD by a mechanism that remains unclear. Here, we show
      that the level of REST mRNA is increased in HD mice and in NG108 cells
      differentiated into neuronal-like cells and expressing a toxic mHtt fragment.
      Using luciferase reporter gene assay, we delimited the REST promoter regions
      essential for mHtt-mediated REST upregulation and found that they contain Sp
      factor binding sites. We provide evidence that Sp1 and Sp3 bind REST promoter and
      interplay to fine-tune REST transcription. In undifferentiated NG108 cells, Sp1
      and Sp3 have antagonistic effect, Sp1 acting as an activator and Sp3 as a
      repressor. Upon neuronal differentiation, we show that the amount and ratio of
      Sp1/Sp3 proteins decline, as does REST expression, and that the transcriptional
      role of Sp3 shifts toward a weak activator. Therefore, our results provide new
      molecular information to the transcriptional regulation of REST during neuronal
      differentiation. Importantly, specific knockdown of Sp1 abolishes REST
      upregulation in NG108 neuronal-like cells expressing mHtt. Our data together with
      earlier reports suggest that mHtt triggers a pathogenic cascade involving Sp1
      activation, which leads to REST upregulation and repression of neuronal genes.

PMID- 21179470
TI  - Photodynamic therapy of tumors can lead to development of systemic antigen
      specific immune response.
AB  - BACKGROUND: The mechanism by which the immune system can effectively recognize
      and destroy tumors is dependent on recognition of tumor antigens. The molecular
      identity of a number of these antigens has recently been identified and several
      immunotherapies have explored them as targets. Photodynamic therapy (PDT) is an
      anti-cancer modality that uses a non-toxic photosensitizer and visible light to
      produce cytotoxic reactive oxygen species that destroy tumors. PDT has been shown
      to lead to local destruction of tumors as well as to induction of anti-tumor
      immune response. METHODOLOGY/PRINCIPAL FINDINGS: We used a pair of equally lethal
      BALB/c colon adenocarcinomas, CT26 wild-type (CT26WT) and CT26.CL25 that
      expressed a tumor antigen, beta-galactosidase (beta-gal), and we treated them
      with vascular PDT. All mice bearing antigen-positive, but not antigen-negative
      tumors were cured and resistant to rechallenge. T lymphocytes isolated from cured
      mice were able to specifically lyse antigen positive cells and recognize the
      epitope derived from beta-galactosidase antigen. PDT was capable of destroying
      distant, untreated, established, antigen-expressing tumors in 70% of the mice.
      The remaining 30% escaped destruction due to loss of expression of tumor antigen.
      The PDT anti-tumor effects were completely abrogated in the absence of the
      adaptive immune response. CONCLUSION: Understanding the role of antigen
      expression in PDT immune response may allow application of PDT in metastatic as
      well as localized disease. To the best of our knowledge, this is the first time
      that PDT has been shown to lead to systemic, antigen- specific anti-tumor
      immunity.

PMID- 21179471
TI  - Down-regulation of mir-424 contributes to the abnormal angiogenesis via MEK1 and
      cyclin E1 in senile hemangioma: its implications to therapy.
AB  - BACKGROUND: Senile hemangioma, so-called cherry angioma, is known as the most
      common vascular anomalies specifically seen in the aged skin. The pathogenesis of
      its abnormal angiogenesis is still unclear. METHODOLOGY/PRINCIPAL FINDINGS: In
      this study, we found that senile hemangioma consisted of clusters of proliferated
      small vascular channels in upper dermis, indicating that this tumor is
      categorized as a vascular tumor. We then investigated the mechanism of
      endothelial proliferation in senile hemangioma, focusing on microRNA (miRNA).
      miRNA PCR array analysis revealed the mir-424 level in senile hemangioma was
      lower than in other vascular anomalies. Protein expression of MEK1 and cyclin E1,
      the predicted target genes of mir-424, was increased in senile hemangioma
      compared to normal skin or other anomalies, but their mRNA levels were not. The
      inhibition of mir-424 in normal human dermal microvascular ECs (HDMECs) using
      specific inhibitor in vitro resulted in the increase of protein expression of
      MEK1 or cyclin E1, while mRNA levels were not affected by the inhibitor. Specific
      inhibitor of mir-424 also induced the cell proliferation of HDMECs significantly,
      while the cell number was decreased by the transfection of siRNA for MEK1 or
      cyclin E1. CONCLUSIONS/SIGNIFICANCE: Taken together, decreased mir-424 expression
      and increased levels of MEK1 or cyclin E1 in senile hemangioma may cause abnormal
      cell proliferation in the tumor. Senile hemangioma may be the good model for
      cutaneous angiogenesis. Investigation of senile hemangioma and the regulatory
      mechanisms of angiogenesis by miRNA in the aged skin may lead to new treatments
      using miRNA by the transfection into senile hemangioma.

PMID- 21179473
TI  - Thermal acclimation of heart rates in reptilian embryos.
AB  - In many reptiles, the thermal regimes experienced by eggs in natural nests vary
      as a function of ambient weather and location, and this variation has important
      impacts on patterns of embryonic development. Recent advances in non-invasive
      measurement of embryonic heart rates allow us to answer a long-standing puzzle in
      reptilian developmental biology: Do the metabolic and developmental rates of
      embryos acclimate to local incubation regimes, as occurs for metabolic
      acclimation by post-hatching reptiles? Based on a strong correlation between
      embryonic heart rate and oxygen consumption, we used heart rates as a measure of
      metabolic rate. We demonstrate acclimation of heart rates relative to temperature
      in embryos of one turtle, one snake and one lizard species that oviposit in
      relatively deep nests, but found no acclimation in another lizard species that
      uses shallow (and hence, highly thermally variable) nests. Embryonic thermal
      acclimation thus is widespread, but not ubiquitous, within reptiles.

PMID- 21179472
TI  - Histone deacetylase inhibitors downregulate checkpoint kinase 1 expression to
      induce cell death in non-small cell lung cancer cells.
AB  - BACKGROUND: Histone deacetylase inhibitors (HDACis) are promising anticancer
      drugs; however, the molecular mechanisms leading to HDACi-induced cell death have
      not been well understood and no clear mechanism of resistance has been elucidated
      to explain limited efficacy of HDACis in clinical trials. METHODS AND FINDINGS:
      Here, we show that protein levels of checkpoint kinase 1 (Chk1), which has a
      major role in G(2) cell cycle checkpoint regulation, was markedly reduced at the
      protein and transcriptional levels in lung cancer cells treated with pan-and
      selective HDACis LBH589, scriptaid, valproic acid, apicidin, and MS-275. In HDACi
      treated cells Chk1 function was impaired as determined by decreased inhibitory
      phosphorylation of cdc25c and its downstream target cdc2 and increased expression
      of cdc25A and phosphorylated histone H3, a marker of mitotic entry. In time
      course experiments, Chk1 downregulation occurred after HDACi treatment, preceding
      apoptosis. Ectopic expression of Chk1 overcame HDACi-induced cell death, and
      pretreating cells with the cdc2 inhibitor purvalanol A blocked entry into mitosis
      and prevented cell death by HDACis. Finally, pharmacological inhibition of Chk1
      showed strong synergistic effect with LBH589 in lung cancer cells. CONCLUSIONS:
      These results define a pathway through which Chk1 inhibition can mediate HDACi
      induced mitotic entry and cell death and suggest that Chk1 could be an early
      pharmacodynamic marker to assess HDACi efficacy in clinical samples.

PMID- 21179474
TI  - Mathematical modeling for the pathogenesis of Alzheimer's disease.
AB  - Despite extensive research, the pathogenesis of neurodegenerative Alzheimer's
      disease (AD) still eludes our comprehension. This is largely due to complex and
      dynamic cross-talks that occur among multiple cell types throughout the aging
      process. We present a mathematical model that helps define critical components of
      AD pathogenesis based on differential rate equations that represent the known
      cross-talks involving microglia, astroglia, neurons, and amyloid-beta (Abeta). We
      demonstrate that the inflammatory activation of microglia serves as a key node
      for progressive neurodegeneration. Our analysis reveals that targeting microglia
      may hold potential promise in the prevention and treatment of AD.

PMID- 21179475
TI  - A key role for E-cadherin in intestinal homeostasis and Paneth cell maturation.
AB  - BACKGROUND: E-cadherin is a major component of adherens junctions. Impaired
      expression of E-cadherin in the small intestine and colon has been linked to a
      disturbed intestinal homeostasis and barrier function. Down-regulation of E
      cadherin is associated with the pathogenesis of infections with enteropathogenic
      bacteria and Crohn's disease. METHODS AND FINDINGS: To genetically clarify the
      function of E-cadherin in intestinal homeostasis and maintenance of the
      epithelial defense line, the Cdh1 gene was conditionally inactivated in the mouse
      intestinal epithelium. Inactivation of the Cdh1 gene in the small intestine and
      colon resulted in bloody diarrhea associated with enhanced apoptosis and cell
      shedding, causing life-threatening disease within 6 days. Loss of E-cadherin led
      cells migrate faster along the crypt-villus axis and perturbed cellular
      differentiation. Maturation and positioning of goblet cells and Paneth cells, the
      main cell lineage of the intestinal innate immune system, was severely disturbed.
      The expression of anti-bacterial cryptidins was reduced and mice showed a
      deficiency in clearing enteropathogenic bacteria from the intestinal lumen.
      CONCLUSION: These results highlight the central function of E-cadherin in the
      maintenance of two components of the intestinal epithelial defense: E-cadherin is
      required for the proper function of the intestinal epithelial lining by providing
      mechanical integrity and is a prerequisite for the proper maturation of Paneth
      and goblet cells.

PMID- 21179476
TI  - Human antibody responses to the Anopheles salivary gSG6-P1 peptide: a novel tool
      for evaluating the efficacy of ITNs in malaria vector control.
AB  - To optimize malaria control, WHO has prioritised the need for new indicators to
      evaluate the efficacy of malaria vector control strategies. The gSG6-P1 peptide
      from gSG6 protein of Anopheles gambiae salivary glands was previously designed as
      a specific salivary sequence of malaria vector species. It was shown that the
      quantification of human antibody (Ab) responses to Anopheles salivary proteins in
      general and especially to the gSG6-P1 peptide was a pertinent biomarker of human
      exposure to Anopheles. The present objective was to validate this indicator in
      the evaluation of the efficacy of Insecticide Treated Nets (ITNs). A longitudinal
      evaluation, including parasitological, entomological and immunological
      assessments, was conducted on children and adults from a malaria-endemic area
      before and after the introduction of ITNs. Significant decrease of anti-gSG6-P1
      IgG response was observed just after the efficient ITNs use. Interestingly,
      specific IgG Ab level was especially pertinent to evaluate a short-time period of
      ITNs efficacy and at individual level. However, specific IgG rose back up within
      four months as correct ITN use waned. IgG responses to one salivary peptide could
      constitute a reliable biomarker for the evaluation of ITN efficacy, at short- and
      long-term use, and provide a valuable tool in malaria vector control based on a
      real measurement of human-vector contact.

PMID- 21179477
TI  - A dual platform approach to transcript discovery for the planarian Schmidtea
      mediterranea to establish RNAseq for stem cell and regeneration biology.
AB  - The use of planarians as a model system is expanding and the mechanisms that
      control planarian regeneration are being elucidated. The planarian Schmidtea
      mediterranea in particular has become a species of choice. Currently the
      planarian research community has access to this whole genome sequencing project
      and over 70,000 expressed sequence tags. However, the establishment of massively
      parallel sequencing technologies has provided the opportunity to define genetic
      content, and in particular transcriptomes, in unprecedented detail. Here we apply
      this approach to the planarian model system. We have sequenced, mapped and
      assembled 581,365 long and 507,719,814 short reads from RNA of intact and mixed
      stages of the first 7 days of planarian regeneration. We used an iterative
      mapping approach to identify and define de novo splice sites with short reads and
      increase confidence in our transcript predictions. We more than double the number
      of transcripts currently defined by publicly available ESTs, resulting in a
      collection of 25,053 transcripts described by combining platforms. We also
      demonstrate the utility of this collection for an RNAseq approach to identify
      potential transcripts that are enriched in neoblast stem cells and their progeny
      by comparing transcriptome wide expression levels between irradiated and intact
      planarians. Our experiments have defined an extensive planarian transcriptome
      that can be used as a template for RNAseq and can also help to annotate the S.
      mediterranea genome. We anticipate that suites of other 'omic approaches will
      also be facilitated by building on this comprehensive data set including RNAseq
      across many planarian regenerative stages, scenarios, tissues and phenotypes
      generated by RNAi.

PMID- 21179478
TI  - A low percent ethanol method for immobilizing planarians.
AB  - Planarians have recently become a popular model system for the study of adult
      stem cells, regeneration and polarity. The system is attractive for both
      undergraduate and graduate research labs, since planarian colonies are low cost
      and easy to maintain. Also in situ hybridization, immunofluorescence and RNA
      interference (RNAi) gene knockdown techniques have been developed for planarian
      studies. However, imaging of live worms (particularly at high magnifications) is
      difficult because animals are strongly photophobic; they quickly move away from
      light sources and out of frame. The current methods available to inhibit movement
      in planarians include RNAi injection and exposure to cold temperatures. The
      former is labor and time intensive, while the latter precludes the use of many
      fluorescent reporter dyes. Here, we report a simple, inexpensive and reversible
      method to immobilize planarians for live imaging. Our data show that a short 1
      hour treatment with 3% ethanol (EtOH) is sufficient to inhibit both the fine and
      gross movements of Schmidtea mediterranea planarians, of the typical size used (4
      6 mm), with full recovery of movement within 3-4 hours. Importantly, EtOH
      treatment did not interfere with regeneration, even after repeated exposure, nor
      lyse epithelial cells (as assayed by H&E staining). We demonstrate that a short
      exposure to a low concentration of EtOH is a quick and effective method of
      immobilizing planarians, one that is easily adaptable to planarians of all sizes
      and will increase the accessibility of live imaging assays to planarian
      researchers.

PMID- 21179479
TI  - Angiopoietin-1 treatment reduces inflammation but does not prevent ventilator
      induced lung injury.
AB  - BACKGROUND: Loss of integrity of the epithelial and endothelial barriers is
      thought to be a prominent feature of ventilator-induced lung injury (VILI). Based
      on its function in vascular integrity, we hypothesize that the angiopoietin (Ang)
      Tie2 system plays a role in the development of VILI. The present study was
      designed to examine the effects of mechanical ventilation on the Ang-Tie2 system
      in lung tissue. Moreover, we evaluated whether treatment with Ang-1, a Tie2
      receptor agonist, protects against inflammation, vascular leakage and impaired
      gas exchange induced by mechanical ventilation. METHODS: Mice were anesthetized,
      tracheotomized and mechanically ventilated for 5 hours with either an inspiratory
      pressure of 10 cmH2O ('low' tidal volume ~7.5 ml/kg; LVT) or 18 cmH2O ('high'
      tidal volume ~15 ml/kg; HVT). At initiation of HVT-ventilation, recombinant human
      Ang-1 was intravenously administered (1 or 4 ug per animal). Non-ventilated mice
      served as controls. RESULTS: HVT-ventilation influenced the Ang-Tie2 system in
      lungs of healthy mice since Ang-1, Ang-2 and Tie2 mRNA were decreased. Treatment
      with Ang-1 increased Akt-phosphorylation indicating Tie2 signaling. Ang-1
      treatment reduced infiltration of granulocytes and expression of keratinocyte
      derived chemokine (KC), macrophage inflammatory protein (MIP)-2, monocyte
      chemotactic protein (MCP)-1 and interleukin (IL)-1beta caused by HVT-ventilation.
      Importantly, Ang-1 treatment did not prevent vascular leakage and impaired gas
      exchange in HVT-ventilated mice despite inhibition of inflammation, vascular
      endothelial growth factor (VEGF) and Ang-2 expression. CONCLUSIONS: Ang-1
      treatment downregulates pulmonary inflammation, VEGF and Ang-2 expression but
      does not protect against vascular leakage and impaired gas exchange induced by
      HVT-ventilation.

PMID- 21179480
TI  - Observing the observer (I): meta-bayesian models of learning and decision-making.
AB  - In this paper, we present a generic approach that can be used to infer how
      subjects make optimal decisions under uncertainty. This approach induces a
      distinction between a subject's perceptual model, which underlies the
      representation of a hidden "state of affairs" and a response model, which
      predicts the ensuing behavioural (or neurophysiological) responses to those
      inputs. We start with the premise that subjects continuously update a
      probabilistic representation of the causes of their sensory inputs to optimise
      their behaviour. In addition, subjects have preferences or goals that guide
      decisions about actions given the above uncertain representation of these hidden
      causes or state of affairs. From a Bayesian decision theoretic perspective,
      uncertain representations are so-called "posterior" beliefs, which are influenced
      by subjective "prior" beliefs. Preferences and goals are encoded through a "loss"
      (or "utility") function, which measures the cost incurred by making any
      admissible decision for any given (hidden) state of affair. By assuming that
      subjects make optimal decisions on the basis of updated (posterior) beliefs and
      utility (loss) functions, one can evaluate the likelihood of observed behaviour.
      Critically, this enables one to "observe the observer", i.e. identify (context-
      or subject-dependent) prior beliefs and utility-functions using psychophysical or
      neurophysiological measures. In this paper, we describe the main theoretical
      components of this meta-Bayesian approach (i.e. a Bayesian treatment of Bayesian
      decision theoretic predictions). In a companion paper ('Observing the observer
      (II): deciding when to decide'), we describe a concrete implementation of it and
      demonstrate its utility by applying it to simulated and real reaction time data
      from an associative learning task.

PMID- 21179481
TI  - Enumeration of functional T-cell subsets by fluorescence-immunospot defines
      signatures of pathogen burden in tuberculosis.
AB  - BACKGROUND: IFN-gamma and IL-2 cytokine-profiles define three functional T-cell
      subsets which may correlate with pathogen load in chronic intracellular
      infections. We therefore investigated the feasibility of the immunospot platform
      to rapidly enumerate T-cell subsets by single-cell IFN-gamma/IL-2 cytokine
      profiling and establish whether immunospot-based T-cell signatures distinguish
      different clinical stages of human tuberculosis infection. METHODS: We used
      fluorophore-labelled anti-IFN-gamma and anti-IL-2 antibodies with digital overlay
      of spatially-mapped colour-filtered images to enumerate dual and single cytokine
      secreting M. tuberculosis antigen-specific T-cells in tuberculosis patients and
      in latent tuberculosis infection (LTBI). We validated results against established
      measures of cytokine-secreting T-cells. RESULTS: Fluorescence-immunospot
      correlated closely with single-cytokine enzyme-linked-immunospot for IFN-gamma
      secreting T-cells and IL-2-secreting T-cells and flow-cytometry-based detection
      of dual IFN-gamma/IL-2-secreting T-cells. The untreated tuberculosis signature
      was dominated by IFN-gamma-only-secreting T-cells which shifted consistently in
      longitudinally-followed patients during treatment to a signature dominated by
      dual IFN-gamma/IL-2-secreting T-cells in treated patients. The LTBI signature
      differed from active tuberculosis, with higher proportions of IL-2-only and IFN
      gamma/IL-2-secreting T-cells and lower proportions of IFN-gamma-only-secreting T
      cells. CONCLUSIONS: Fluorescence-immunospot is a quantitative, accurate measure
      of functional T-cell subsets; identification of cytokine-signatures of pathogen
      burden, distinct clinical stages of M. tuberculosis infection and long-term
      immune containment suggests application for treatment monitoring and vaccine
      evaluation.

PMID- 21179482
TI  - Evaluating the relationship between spermatogenic silencing of the X chromosome
      and evolution of the Y chromosome in chimpanzee and human.
AB  - Chimpanzees and humans are genetically very similar, with the striking exception
      of their Y chromosomes, which have diverged tremendously. The male-specific
      region (MSY), representing the greater part of the Y chromosome, is inherited
      from father to son in a clonal fashion, with natural selection acting on the MSY
      as a unit. Positive selection might involve the performance of the MSY in
      spermatogenesis. Chimpanzees have a highly polygamous mating behavior, so that
      sperm competition is thought to provide a strong selective force acting on the Y
      chromosome in the chimpanzee lineage. In consequence of evolution of the
      heterologous sex chromosomes in mammals, meiotic sex chromosome inactivation
      (MSCI) results in a transcriptionally silenced XY body in male meiotic prophase,
      and subsequently also in postmeiotic repression of the sex chromosomes in haploid
      spermatids. This has evolved to a situation where MSCI has become a prerequisite
      for spermatogenesis. Here, by analysis of microarray testicular expression data
      representing a small number of male chimpanzees and men, we obtained information
      indicating that meiotic and postmeiotic X chromosome silencing might be more
      effective in chimpanzee than in human spermatogenesis. From this, we suggest that
      the remarkable reorganization of the chimpanzee Y chromosome, compared to the
      human Y chromosome, might have an impact on its meiotic interactions with the X
      chromosome and thereby on X chromosome silencing in spermatogenesis. Further
      studies will be required to address comparative functional aspects of MSCI in
      chimpanzee, human, and other placental mammals.

PMID- 21179483
TI  - Perturbation of host nuclear membrane component RanBP2 impairs the nuclear import
      of human immunodeficiency virus -1 preintegration complex (DNA).
AB  - HIV-1 is a RNA virus that requires an intermediate DNA phase via reverse
      transcription (RT) step in order to establish productive infection in the host
      cell. The nascent viral DNA synthesized via RT step and the preformed viral
      proteins are assembled into pre-integration complex (PIC) in the cell cytoplasm.
      To integrate the viral DNA into the host genome, the PIC must cross cell nuclear
      membrane through the nuclear pore complex (NPC). RanBP2, also known as Nup358, is
      a major component of the cytoplasmic filaments that emanates from the nuclear
      pore complex and has been implicated in various nucleo-cytoplasmic transport
      pathways including those for HIV Rev-protein. We sought to investigate the role
      of RanBP2 in HIV-1 replication. In our investigations, we found that RanBP2
      depletion via RNAi resulted in profound inhibition of HIV-1 infection and played
      a pivotal role in the nuclear entry of HIV DNA. More precisely, there was a
      profound decline in 2-LTR DNA copies (marker for nuclear entry of HIV DNA) and an
      unchanged level of viral reverse transcription in RanBP2-ablated HIV-infected
      cells compared to RanBP3-depleted or non-specific siRNA controls. We further
      demonstrated that the function of Rev was unaffected in RanBP2-depleted latently
      HIV infected cells (reactivated). We also serendipitously found that RanBP2
      depletion inhibited the global ectopic gene expression. In conclusion, RanBP2 is
      a host factor that is involved in the nuclear import of HIV-1 PIC (DNA), but is
      not critical to the nuclear export of the viral mRNAs or nucleo-cytoplasmic
      shuttling of Rev. RanBP2 could be a potential target for efficient inhibition of
      HIV.

PMID- 21179484
TI  - Observing the observer (II): deciding when to decide.
AB  - In a companion paper [1], we have presented a generic approach for inferring how
      subjects make optimal decisions under uncertainty. From a Bayesian decision
      theoretic perspective, uncertain representations correspond to "posterior"
      beliefs, which result from integrating (sensory) information with subjective
      "prior" beliefs. Preferences and goals are encoded through a "loss" (or
      "utility") function, which measures the cost incurred by making any admissible
      decision for any given (hidden or unknown) state of the world. By assuming that
      subjects make optimal decisions on the basis of updated (posterior) beliefs and
      utility (loss) functions, one can evaluate the likelihood of observed behaviour.
      In this paper, we describe a concrete implementation of this meta-Bayesian
      approach (i.e. a Bayesian treatment of Bayesian decision theoretic predictions)
      and demonstrate its utility by applying it to both simulated and empirical
      reaction time data from an associative learning task. Here, inter-trial
      variability in reaction times is modelled as reflecting the dynamics of the
      subjects' internal recognition process, i.e. the updating of representations
      (posterior densities) of hidden states over trials while subjects learn
      probabilistic audio-visual associations. We use this paradigm to demonstrate that
      our meta-Bayesian framework allows for (i) probabilistic inference on the
      dynamics of the subject's representation of environmental states, and for (ii)
      model selection to disambiguate between alternative preferences (loss functions)
      human subjects could employ when dealing with trade-offs, such as between speed
      and accuracy. Finally, we illustrate how our approach can be used to quantify
      subjective beliefs and preferences that underlie inter-individual differences in
      behaviour.

PMID- 21179485
TI  - Profiling of VEGFs and VEGFRs as prognostic factors in soft tissue sarcoma: VEGFR
      3 is an independent predictor of poor prognosis.
AB  - BACKGROUND: In non-gastrointestinal stromal tumor soft tissue sarcoma (non-GIST
      STS) optimal treatment is surgery with wide resection margins. Vascular
      endothelial growth factors (VEGFs) and receptors (VEGFRs) are known to be key
      players in the initiation of angiogenesis and lymphangiogenesis. This study
      investigates the prognostic impact of VEGFs and VEGFRs in non-GIST STS with wide
      and non-wide resection margins. METHODS: Tumor samples from 249 patients with non
      GIST STS were obtained and tissue microarrays were constructed for each specimen.
      Immunohistochemistry was used to evaluate the expressions of VEGF-A, -C and -D
      and VEGFR-1, -2 and -3. RESULTS: In the univariate analyses, VEGF-A (P=0.040) in
      the total material, and VEGF-A (P=0.018), VEGF-C (P=0.025) and VEGFR-3 (P=0.027)
      in the subgroup with wide resection margins, were significant negative prognostic
      indicators of disease-specific survival (DSS). In the multivariate analysis, high
      expression of VEGFR-3 (P=0.042, HR=1.907, 95% CI 1.024-3.549) was an independent
      significant negative prognostic marker for DSS among patients with wide resection
      margins. CONCLUSION: VEGFR-3 is a strong and independent negative prognostic
      marker for non-GIST STSs with wide resection margins.

PMID- 21179486
TI  - Molecular phylogeny restores the supra-generic subdivision of homoscleromorph
      sponges (Porifera, Homoscleromorpha).
AB  - BACKGROUND: Homoscleromorpha is the fourth major sponge lineage, recently
      recognized to be distinct from the Demospongiae. It contains <100 described
      species of exclusively marine sponges that have been traditionally subdivided
      into 7 genera based on morphological characters. Because some of the
      morphological features of the homoscleromorphs are shared with eumetazoans and
      are absent in other sponges, the phylogenetic position of the group has been
      investigated in several recent studies. However, the phylogenetic relationships
      within the group remain unexplored by modern methods. METHODOLOGY/PRINCIPAL
      FINDINGS: Here we describe the first molecular phylogeny of Homoscleromorpha
      based on nuclear (18S and 28S rDNA) and complete mitochondrial DNA sequence data
      that focuses on inter-generic relationships. Our results revealed two robust
      clades within this group, one containing the spiculate species (genera Plakina,
      Plakortis, Plakinastrella and Corticium) and the other containing aspiculate
      species (genera Oscarella and Pseudocorticium), thus rejecting a close
      relationship between Pseudocorticium and Corticium. Among the spiculate species,
      we found affinities between the Plakortis and Plakinastrella genera, and between
      the Plakina and Corticium. The validity of these clades is furthermore supported
      by specific morphological characters, notably the type of spicules. Furthermore,
      the monophyly of the Corticium genus is supported while the monophyly of Plakina
      is not. CONCLUSIONS/SIGNIFICANCE: As the result of our study we propose to
      restore the pre-1995 subdivision of Homoscleromorpha into two families:
      Plakinidae Schulze, 1880 for spiculate species and Oscarellidae Lendenfeld, 1887
      for aspiculate species that had been rejected after the description of the genus
      Pseudocorticium. We also note that the two families of homoscleromorphs exhibit
      evolutionary stable, but have drastically distinct mitochondrial genome
      organizations that differ in gene content and gene order.

PMID- 21179487
TI  - Metabolic activity and mRNA levels of human cardiac CYP450s involved in drug
      metabolism.
AB  - BACKGROUND: Tissue-specific expression of CYP450s can regulate the intracellular
      concentration of drugs and explain inter-subject variability in drug action. The
      overall objective of our study was to determine in a large cohort of samples,
      mRNA levels and CYP450 activity expressed in the human heart. METHODOLOGY: CYP450
      mRNA levels were determined by RTPCR in left ventricular samples (n = 68) of
      explanted hearts from patients with end-stage heart failure. Samples were
      obtained from ischemic and non-ischemic hearts. In some instances (n = 7),
      samples were available from both the left and right ventricles. A technique for
      the preparation of microsomes from human heart tissue was developed and CYP450
      dependent activity was determined using verapamil enantiomers as probe-drug
      substrates. PRINCIPAL FINDINGS: Our results show that CYP2J2 mRNA was the most
      abundant isoform in all human heart left ventricular samples tested. Other CYP450
      mRNAs of importance were CYP4A11, CYP2E1, CYP1A1 and CYP2C8 mRNAs while CYP2B6
      and CYP2C9 mRNAs were present at low levels in only some of the hearts analyzed.
      CYP450 mRNAs did not differ between ischemic and non-ischemic hearts and appeared
      to be present at similar levels in the left and right ventricles. Incubation of
      verapamil with heart microsomes led to the formation of nine CYP450-dependent
      metabolites: a major finding was the observation that stereoselectivity was
      reversed compared to human liver microsomes, in which the R-enantiomer is
      metabolized to a greater extent. CONCLUSIONS: This study determined cardiac mRNA
      levels of various CYP450 isozymes involved in drug metabolism and demonstrated
      the prevalent expression of CYP2J2 mRNA. It revealed that cardiomyocytes can
      efficiently metabolize drugs and that cardiac CYP450s are highly relevant with
      regard to clearance of drugs in the heart. Our results support the claim that
      drug metabolism in the vicinity of a drug effector site can modulate drug
      effects.

PMID- 21179488
TI  - Coxiella burnetii, the agent of Q fever, replicates within trophoblasts and
      induces a unique transcriptional response.
AB  - Q fever is a zoonosis caused by Coxiella burnetii, an obligate intracellular
      bacterium typically found in myeloid cells. The infection is a source of severe
      obstetrical complications in humans and cattle and can undergo chronic evolution
      in a minority of pregnant women. Because C. burnetii is found in the placentas of
      aborted fetuses, we investigated the possibility that it could infect
      trophoblasts. Here, we show that C. burnetii infected and replicated in BeWo
      trophoblasts within phagolysosomes. Using pangenomic microarrays, we found that
      C. burnetii induced a specific transcriptomic program. This program was
      associated with the modulation of inflammatory responses that were shared with
      inflammatory agonists, such as TNF, and more specific responses involving genes
      related to pregnancy development, including EGR-1 and NDGR1. In addition, C.
      burnetii stimulated gene networks organized around the IL-6 and IL-13 pathways,
      which both modulate STAT3. Taken together, these results revealed that
      trophoblasts represent a protective niche for C. burnetii. The activation program
      induced by C. burnetii in trophoblasts may allow bacterial replication but seems
      unable to interfere with the development of normal pregnancy. Such
      pathophysiologocal processes should require the activation of immune placental
      cells associated with trophoblasts.

PMID- 21179489
TI  - Dispersal of biofilms by secreted, matrix degrading, bacterial DNase.
AB  - Microbial biofilms are composed of a hydrated matrix of biopolymers including
      polypeptides, polysaccharides and nucleic acids and act as a protective barrier
      and microenvironment for the inhabiting microbes. While studying marine biofilms,
      we observed that supernatant produced by a marine isolate of Bacillus
      licheniformis was capable of dispersing bacterial biofilms. We investigated the
      source of this activity and identified the active compound as an extracellular
      DNase (NucB). We have shown that this enzyme rapidly breaks up the biofilms of
      both Gram-positive and Gram-negative bacteria. We demonstrate that bacteria can
      use secreted nucleases as an elegant strategy to disperse established biofilms
      and to prevent de novo formation of biofilms of competitors. DNA therefore plays
      an important dynamic role as a reversible structural adhesin within the biofilm.

PMID- 21179490
TI  - Vitamin D induction of the human antimicrobial Peptide cathelicidin in the
      urinary bladder.
AB  - The urinary tract is frequently being exposed to potential pathogens and rapid
      defence mechanisms are therefore needed. Cathelicidin, a human antimicrobial
      peptide is expressed and secreted by bladder epithelial cells and protects the
      urinary tract from infection. Here we show that vitamin D can induce cathelicidin
      in the urinary bladder. We analyzed bladder tissue from postmenopausal women for
      expression of cathelicidin, before and after a three-month period of
      supplementation with 25-hydroxyvitamin D3 (25D3). Cell culture experiments were
      performed to elucidate the mechanisms for cathelicidin induction. We observed
      that, vitamin D per se did not up-regulate cathelicidin in serum or in bladder
      tissue of the women in this study. However, when the bladder biopsies were
      infected with uropathogenic E. coli (UPEC), a significant increase in
      cathelicidin expression was observed after 25D3 supplementation. This observation
      was confirmed in human bladder cell lines, even though here, cathelicidin
      induction occurred irrespectively of infection. Vitamin D treated bladder cells
      exerted an increased antibacterial effect against UPEC and colocalization to
      cathelicidin indicated the relevance of this peptide. In the light of the rapidly
      growing problem of resistance to common urinary tract antibiotics, we suggest
      that vitamin D may be a potential complement in the prevention of UTI.

PMID- 21179491
TI  - CSPG is a secreted factor that stimulates neural stem cell survival possibly by
      enhanced EGFR signaling.
AB  - Understanding how autocrine/paracrine factors regulate neural stem cell (NSC)
      survival and growth is fundamental to the utilization of these cells for
      therapeutic applications and as cellular models for the brain. In vitro, NSCs can
      be propagated along with neural progenitors (NPs) as neurospheres (nsphs). The
      nsph conditioned medium (nsph-CM) contains cell-secreted factors that can
      regulate NSC behavior. However, the identity and exact function of these factors
      within the nsph-CM has remained elusive. We analyzed the nsph-CM by mass
      spectrometry and identified DSD-1-proteoglycan, a chondroitin sulfate
      proteoglycan (CSPG), apolipoprotein E (ApoE) and cystatin C as components of the
      nsph-CM. Using clonal assays we show that CSPG and ApoE are responsible for the
      ability of the nsph-CM to stimulate nsph formation whereas cystatin C is not
      involved. Clonal nsphs generated in the presence of CSPG show more than four-fold
      increase in NSCs. Thus CSPG specifically enhances the survival of NSCs. CSPG also
      stimulates the survival of embryonic stem cell (ESC)-derived NSCs, and thus may
      be involved in the developmental transition of ESCs to NSCs. In addition to its
      role in NSC survival, CSPG maintains the three dimensional structure of nsphs.
      Lastly, CSPG's effects on NSC survival may be mediated by enhanced signaling via
      EGFR, JAK/STAT3 and PI3K/Akt pathways.

PMID- 21179492
TI  - Neural correlates of experience-induced deficits in learned vocal communication.
AB  - Songbirds are one of the few vertebrate groups (including humans) that evolved
      the ability to learn vocalizations. During song learning, social interactions
      with adult models are crucial and young songbirds raised without direct contacts
      with adults typically produce abnormal songs showing phonological and syntactical
      deficits. This raises the question of what functional representation of their
      vocalizations such deprived animals develop. Here we show that young starlings
      that we raised without any direct contact with adults not only failed to
      differentiate starlings' typical song classes in their vocalizations but also
      failed to develop differential neural responses to these songs. These deficits
      appear to be linked to a failure to acquire songs' functions and may provide a
      model for abnormal development of communicative skills, including speech.

PMID- 21179493
TI  - Male circumcision in the general population of Kisumu, Kenya: beliefs about
      protection, risk behaviors, HIV, and STIs.
AB  - Using a population-based survey we examined the behaviors, beliefs, and HIV/HSV-2
      serostatus of men and women in the traditionally non-circumcising community of
      Kisumu, Kenya prior to establishment of voluntary medical male circumcision
      services. A total of 749 men and 906 women participated. Circumcision status was
      not associated with HIV/HSV-2 infection nor increased high risk sexual behaviors.
      In males, preference for being or becoming circumcised was associated with
      inconsistent condom use and increased lifetime number of sexual partners.
      Preference for circumcision was increased with understanding that circumcised men
      are less likely to become infected with HIV.

PMID- 21179494
TI  - A porcine adenovirus with low human seroprevalence is a promising alternative
      vaccine vector to human adenovirus 5 in an H5N1 virus disease model.
AB  - Human adenovirus 5 (AdHu5) vectors are robust vaccine platforms however the
      presence of naturally-acquired neutralizing antibodies may reduce vector efficacy
      and potential for re-administration. This study evaluates immune responses and
      protection following vaccination with a replication-incompetent porcine
      adenovirus 3 (PAV3) vector as an alternative vaccine to AdHu5 using an avian
      influenza H5N1 disease model. Vaccine efficacy was evaluated in BALB/c mice
      following vaccination with different doses of the PAV3 vector expressing an
      optimized A/Hanoi/30408/2005 H5N1 hemagglutinin antigen (PAV3-HA) and compared
      with an AdHu5-HA control. PAV3-HA rapidly generated antibody responses, with
      significant neutralizing antibody titers on day 21, and stronger cellular immune
      responses detected on day 8, compared to AdHu5-HA. The PAV3-HA vaccine,
      administered 8 days before challenge, demonstrated improved survival and lower
      virus load. Evaluation of long-term vaccine efficacy at 12 months post
      vaccination showed better protection with the PAV3-HA than with the AdHu5-HA
      vaccine. Importantly, as opposed to AdHu5, PAV3 vector was not significantly
      neutralized by human antibodies pooled from over 10,000 individuals. Overall,
      PAV3-based vector is capable of mediating swift, strong immune responses and
      offer a promising alternative to AdHu5.

PMID- 21179495
TI  - Nuclear receptor expression defines a set of prognostic biomarkers for lung
      cancer.
AB  - BACKGROUND: The identification of prognostic tumor biomarkers that also would
      have potential as therapeutic targets, particularly in patients with early stage
      disease, has been a long sought-after goal in the management and treatment of
      lung cancer. The nuclear receptor (NR) superfamily, which is composed of 48
      transcription factors that govern complex physiologic and pathophysiologic
      processes, could represent a unique subset of these biomarkers. In fact, many
      members of this family are the targets of already identified selective receptor
      modulators, providing a direct link between individual tumor NR quantitation and
      selection of therapy. The goal of this study, which begins this overall strategy,
      was to investigate the association between mRNA expression of the NR superfamily
      and the clinical outcome for patients with lung cancer, and to test whether a
      tumor NR gene signature provided useful information (over available clinical
      data) for patients with lung cancer. METHODS AND FINDINGS: Using quantitative
      real-time PCR to study NR expression in 30 microdissected non-small-cell lung
      cancers (NSCLCs) and their pair-matched normal lung epithelium, we found great
      variability in NR expression among patients' tumor and non-involved lung
      epithelium, found a strong association between NR expression and clinical
      outcome, and identified an NR gene signature from both normal and tumor tissues
      that predicted patient survival time and disease recurrence. The NR signature
      derived from the initial 30 NSCLC samples was validated in two independent
      microarray datasets derived from 442 and 117 resected lung adenocarcinomas. The
      NR gene signature was also validated in 130 squamous cell carcinomas. The
      prognostic signature in tumors could be distilled to expression of two NRs, short
      heterodimer partner and progesterone receptor, as single gene predictors of NSCLC
      patient survival time, including for patients with stage I disease. Of equal
      interest, the studies of microdissected histologically normal epithelium and
      matched tumors identified expression in normal (but not tumor) epithelium of
      NGFIB3 and mineralocorticoid receptor as single gene predictors of good
      prognosis. CONCLUSIONS: NR expression is strongly associated with clinical
      outcomes for patients with lung cancer, and this expression profile provides a
      unique prognostic signature for lung cancer patient survival time, particularly
      for those with early stage disease. This study highlights the potential use of
      NRs as a rational set of therapeutically tractable genes as theragnostic
      biomarkers, and specifically identifies short heterodimer partner and
      progesterone receptor in tumors, and NGFIB3 and MR in non-neoplastic lung
      epithelium, for future detailed translational study in lung cancer. Please see
      later in the article for the Editors' Summary.

PMID- 21179496
TI  - Clinical benefits, costs, and cost-effectiveness of neonatal intensive care in
      Mexico.
AB  - BACKGROUND: Neonatal intensive care improves survival, but is associated with
      high costs and disability amongst survivors. Recent health reform in Mexico
      launched a new subsidized insurance program, necessitating informed choices on
      the different interventions that might be covered by the program, including
      neonatal intensive care. The purpose of this study was to estimate the clinical
      outcomes, costs, and cost-effectiveness of neonatal intensive care in Mexico.
      METHODS AND FINDINGS: A cost-effectiveness analysis was conducted using a
      decision analytic model of health and economic outcomes following preterm birth.
      Model parameters governing health outcomes were estimated from Mexican vital
      registration and hospital discharge databases, supplemented with meta-analyses
      and systematic reviews from the published literature. Costs were estimated on the
      basis of data provided by the Ministry of Health in Mexico and World Health
      Organization price lists, supplemented with published studies from other
      countries as needed. The model estimated changes in clinical outcomes, life
      expectancy, disability-free life expectancy, lifetime costs, disability-adjusted
      life years (DALYs), and incremental cost-effectiveness ratios (ICERs) for
      neonatal intensive care compared to no intensive care. Uncertainty around the
      results was characterized using one-way sensitivity analyses and a multivariate
      probabilistic sensitivity analysis. In the base-case analysis, neonatal intensive
      care for infants born at 24-26, 27-29, and 30-33 weeks gestational age prolonged
      life expectancy by 28, 43, and 34 years and averted 9, 15, and 12 DALYs, at
      incremental costs per infant of US$11,400, US$9,500, and US$3,000, respectively,
      compared to an alternative of no intensive care. The ICERs of neonatal intensive
      care at 24-26, 27-29, and 30-33 weeks were US$1,200, US$650, and US$240, per DALY
      averted, respectively. The findings were robust to variation in parameter values
      over wide ranges in sensitivity analyses. CONCLUSIONS: Incremental cost
      effectiveness ratios for neonatal intensive care imply very high value for money
      on the basis of conventional benchmarks for cost-effectiveness analysis. Please
      see later in the article for the Editors' Summary.

PMID- 21179497
TI  - Connecting variability in global transcription rate to mitochondrial variability.
AB  - Populations of genetically identical eukaryotic cells show significant cell-to
      cell variability in gene expression. However, we lack a good understanding of the
      origins of this variation. We have found marked cell-to-cell variability in
      average cellular rates of transcription. We also found marked cell-to-cell
      variability in the amount of cellular mitochondrial mass. We undertook fusion
      studies that suggested that variability in transcription rate depends on small
      diffusible factors. Following this, in vitro studies showed that transcription
      rate has a sensitive dependence on [ATP] but not on the concentration of other
      nucleotide triphosphates (NTPs). Further experiments that perturbed populations
      by changing nutrient levels and available [ATP] suggested this connection holds
      in vivo. We found evidence that cells with higher mitochondrial mass, or higher
      total membrane potential, have a faster rate of transcription per unit volume of
      nuclear material. We also found evidence that transcription rate variability is
      substantially modulated by the presence of anti- or prooxidants. Daughter studies
      showed that a cause of variability in mitochondrial content is apparently
      stochastic segregation of mitochondria at division. We conclude by noting that
      daughters that stochastically inherit a lower mitochondrial mass than their
      sisters have relatively longer cell cycles. Our findings reveal a link between
      variability in energy metabolism and variability in transcription rate.

PMID- 21179498
TI  - High-throughput chemical screen identifies a novel potent modulator of cellular
      circadian rhythms and reveals CKIalpha as a clock regulatory kinase.
AB  - The circadian clock underlies daily rhythms of diverse physiological processes,
      and alterations in clock function have been linked to numerous pathologies. To
      apply chemical biology methods to modulate and dissect the clock mechanism with
      new chemical probes, we performed a circadian screen of ~120,000 uncharacterized
      compounds on human cells containing a circadian reporter. The analysis identified
      a small molecule that potently lengthens the circadian period in a dose-dependent
      manner. Subsequent analysis showed that the compound also lengthened the period
      in a variety of cells from different tissues including the mouse suprachiasmatic
      nucleus, the central clock controlling behavioral rhythms. Based on the prominent
      period lengthening effect, we named the compound longdaysin. Longdaysin was
      amenable for chemical modification to perform affinity chromatography coupled
      with mass spectrometry analysis to identify target proteins. Combined with siRNA
      mediated gene knockdown, we identified the protein kinases CKIdelta, CKIalpha,
      and ERK2 as targets of longdaysin responsible for the observed effect on
      circadian period. Although individual knockdown of CKIdelta, CKIalpha, and ERK2
      had small period effects, their combinatorial knockdown dramatically lengthened
      the period similar to longdaysin treatment. We characterized the role of CKIalpha
      in the clock mechanism and found that CKIalpha-mediated phosphorylation
      stimulated degradation of a clock protein PER1, similar to the function of
      CKIdelta. Longdaysin treatment inhibited PER1 degradation, providing insight into
      the mechanism of longdaysin-dependent period lengthening. Using larval zebrafish,
      we further demonstrated that longdaysin drastically lengthened circadian period
      in vivo. Taken together, the chemical biology approach not only revealed CKIalpha
      as a clock regulatory kinase but also identified a multiple kinase network
      conferring robustness to the clock. Longdaysin provides novel possibilities in
      manipulating clock function due to its ability to simultaneously inhibit several
      key components of this conserved network across species.

PMID- 21179499
TI  - A genetic and functional relationship between T cells and cellular proliferation
      in the adult hippocampus.
AB  - Neurogenesis continues through the adult life of mice in the subgranular zone of
      the dentate gyrus in the hippocampus, but its function remains unclear. Measuring
      cellular proliferation in the hippocampus of 719 outbred heterogeneous stock mice
      revealed a highly significant correlation with the proportions of CD8+ versus
      CD4+ T lymphocyte subsets. This correlation reflected shared genetic loci, with
      the exception of the H-2Ea locus that had a dominant influence on T cell subsets
      but no impact on neurogenesis. Analysis of knockouts and repopulation of TCRalpha
      deficient mice by subsets of T cells confirmed the influence of T cells on adult
      neurogenesis, indicating that CD4+ T cells or subpopulations thereof mediate the
      effect. Our results reveal an organismal impact, broader than hitherto suspected,
      of the natural genetic variation that controls T cell development and
      homeostasis.

PMID- 21179500
TI  - Cancer courts immune response to aid growth.

PMID- 21179501
TI  - Live imaging of innate immune cell sensing of transformed cells in zebrafish
      larvae: parallels between tumor initiation and wound inflammation.
AB  - It has not previously been possible to live image the earliest interactions
      between the host environment and oncogene-transformed cells as they initiate
      formation of cancers within an organism. Here we take advantage of the
      translucency of zebrafish larvae to observe the host innate immune cell response
      as oncogene-transformed melanoblasts and goblet cells multiply within the larval
      skin. Our studies indicate activation of leukocytes at very early stages in
      larvae carrying a transformed cell burden. Locally, we see recruitment of
      neutrophils and macrophages by 48 h post-fertilization, when transformed cells
      are still only singletons or doublets, and soon after this we see intimate
      associations between immune and transformed cells and frequent examples of
      cytoplasmic tethers linking the two cell types, as well as engulfment of
      transformed cells by both neutrophils and macrophages. We show that a major
      component of the signal drawing inflammatory cells to oncogenic HRAS(G12V)
      transformed cells is H(2)O(2), which is also a key damage cue responsible for
      recruiting neutrophils to a wound. Our short-term blocking experiments show that
      preventing recruitment of immune cells at these early stages results in reduced
      growth of transformed cell clones and suggests that immune cells may provide a
      source of trophic support to the transformed cells just as they do at a site of
      tissue repair. These parallels between the inflammatory responses to transformed
      cells and to wounds reinforce the suggestion by others that cancers resemble non
      healing wounds.

PMID- 21179502
TI  - Sex, subdivision, and domestic dispersal of Trypanosoma cruzi lineage I in
      southern Ecuador.
AB  - BACKGROUND: Molecular epidemiology at the community level has an important
      guiding role in zoonotic disease control programmes where genetic markers are
      suitably variable to unravel the dynamics of local transmission. We evaluated the
      molecular diversity of Trypanosoma cruzi, the etiological agent of Chagas
      disease, in southern Ecuador (Loja Province). This kinetoplastid parasite has
      traditionally been a paradigm for clonal population structure in pathogenic
      organisms. However, the presence of naturally occurring hybrids, mitochondrial
      introgression, and evidence of genetic exchange in the laboratory question this
      dogma. METHODOLOGY/PRINCIPAL FINDINGS: Eighty-one parasite isolates from
      domiciliary, peridomiciliary, and sylvatic triatomines and mammals were genotyped
      across 10 variable microsatellite loci. Two discrete parasite populations were
      defined: one predominantly composed of isolates from domestic and peridomestic
      foci, and another predominantly composed of isolates from sylvatic foci. Spatial
      genetic variation was absent from the former, suggesting rapid parasite dispersal
      across our study area. Furthermore, linkage equilibrium between loci, Hardy
      Weinberg allele frequencies at individual loci, and a lack of repeated genotypes
      are indicative of frequent genetic exchange among individuals in the
      domestic/peridomestic population. CONCLUSIONS/SIGNIFICANCE: These data represent
      novel population-level evidence of an extant capacity for sex among natural
      cycles of T. cruzi transmission. As such they have dramatic implications for our
      understanding of the fundamental genetics of this parasite. Our data also
      elucidate local disease transmission, whereby passive anthropogenic domestic
      mammal and triatomine dispersal across our study area is likely to account for
      the rapid domestic/peridomestic spread of the parasite. Finally we discuss how
      this, and the observed subdivision between sympatric sylvatic and
      domestic/peridomestic foci, can inform efforts at Chagas disease control in
      Ecuador.

PMID- 21179503
TI  - The potential economic value of a Trypanosoma cruzi (Chagas disease) vaccine in
      Latin America.
AB  - BACKGROUND: Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi),
      is the leading etiology of non-ischemic heart disease worldwide, with Latin
      America bearing the majority of the burden. This substantial burden and the
      limitations of current interventions have motivated efforts to develop a vaccine
      against T. cruzi. METHODOLOGY/PRINCIPAL FINDINGS: We constructed a decision
      analytic Markov computer simulation model to assess the potential economic value
      of a T. cruzi vaccine in Latin America from the societal perspective. Each
      simulation run calculated the incremental cost-effectiveness ratio (ICER), or the
      cost per disability-adjusted life year (DALY) avoided, of vaccination.
      Sensitivity analyses evaluated the impact of varying key model parameters such as
      vaccine cost (range: $0.50-$200), vaccine efficacy (range: 25%-75%), the cost of
      acute-phase drug treatment (range: $10-$150 to account for variations in acute
      phase treatment regimens), and risk of infection (range: 1%-20%). Additional
      analyses determined the incremental cost of vaccinating an individual and the
      cost per averted congestive heart failure case. Vaccination was considered highly
      cost-effective when the ICER was <=1 times the GDP/capita, still cost-effective
      when the ICER was between 1 and 3 times the GDP/capita, and not cost-effective
      when the ICER was >3 times the GDP/capita. Our results showed vaccination to be
      very cost-effective and often economically dominant (i.e., saving costs as well
      providing health benefits) for a wide range of scenarios, e.g., even when risk of
      infection was as low as 1% and vaccine efficacy was as low as 25%. Vaccinating an
      individual could likely provide net cost savings that rise substantially as risk
      of infection or vaccine efficacy increase. CONCLUSIONS/SIGNIFICANCE: Results
      indicate that a T. cruzi vaccine could provide substantial economic benefit,
      depending on the cost of the vaccine, and support continued efforts to develop a
      human vaccine.

PMID- 21179504
TI  - Responses of human endothelial cells to pathogenic and non-pathogenic Leptospira
      species.
AB  - Leptospirosis is a widespread zoonotic infection that primarily affects residents
      of tropical regions, but causes infections in animals and humans in temperate
      regions as well. The agents of leptospirosis comprise several members of the
      genus Leptospira, which also includes non-pathogenic, saprophytic species.
      Leptospirosis can vary in severity from a mild, non-specific illness to severe
      disease that includes multi-organ failure and widespread endothelial damage and
      hemorrhage. To begin to investigate how pathogenic leptospires affect endothelial
      cells, we compared the responses of two endothelial cell lines to infection by
      pathogenic versus non-pathogenic leptospires. Microarray analyses suggested that
      pathogenic L. interrogans and non-pathogenic L. biflexa triggered changes in
      expression of genes whose products are involved in cellular architecture and
      interactions with the matrix, but that the changes were in opposite directions,
      with infection by L. biflexa primarily predicted to increase or maintain cell
      layer integrity, while L. interrogans lead primarily to changes predicted to
      disrupt cell layer integrity. Neither bacterial strain caused necrosis or
      apoptosis of the cells even after prolonged incubation. The pathogenic L.
      interrogans, however, did result in significant disruption of endothelial cell
      layers as assessed by microscopy and the ability of the bacteria to cross the
      cell layers. This disruption of endothelial layer integrity was abrogated by
      addition of the endothelial protective drug lisinopril at physiologically
      relevant concentrations. These results suggest that, through adhesion of L.
      interrogans to endothelial cells, the bacteria may disrupt endothelial barrier
      function, promoting dissemination of the bacteria and contributing to severe
      disease manifestations. In addition, supplementing antibiotic therapy with
      lisinopril or derivatives with endothelial protective activities may decrease the
      severity of leptospirosis.

PMID- 21179505
TI  - Ecology and transmission of Buruli ulcer disease: a systematic review.
AB  - Buruli ulcer is a neglected emerging disease that has recently been reported in
      some countries as the second most frequent mycobacterial disease in humans after
      tuberculosis. Cases have been reported from at least 32 countries in Africa
      (mainly west), Australia, Southeast Asia, China, Central and South America, and
      the Western Pacific. Large lesions often result in scarring, contractual
      deformities, amputations, and disabilities, and in Africa, most cases of the
      disease occur in children between the ages of 4-15 years. This environmental
      mycobacterium, Mycobacterium ulcerans, is found in communities associated with
      rivers, swamps, wetlands, and human-linked changes in the aquatic environment,
      particularly those created as a result of environmental disturbance such as
      deforestation, dam construction, and agriculture. Buruli ulcer disease is often
      referred to as the "mysterious disease" because the mode of transmission remains
      unclear, although several hypotheses have been proposed. The above review reveals
      that various routes of transmission may occur, varying amongst epidemiological
      setting and geographic region, and that there may be some role for living agents
      as reservoirs and as vectors of M. ulcerans, in particular aquatic insects, adult
      mosquitoes or other biting arthropods. We discuss traditional and non-traditional
      methods for indicting the roles of living agents as biologically significant
      reservoirs and/or vectors of pathogens, and suggest an intellectual framework for
      establishing criteria for transmission. The application of these criteria to the
      transmission of M. ulcerans presents a significant challenge.

PMID- 21179507
TI  - Does collocation inform the impact of collaboration?
AB  - BACKGROUND: It has been shown that large interdisciplinary teams working across
      geography are more likely to be impactful. We asked whether the physical
      proximity of collaborators remained a strong predictor of the scientific impact
      of their research as measured by citations of the resulting publications.
      METHODOLOGY/PRINCIPAL FINDINGS: Articles published by Harvard investigators from
      1993 to 2003 with at least two authors were identified in the domain of
      biomedical science. Each collaboration was geocoded to the precise three
      dimensional location of its authors. Physical distances between any two coauthors
      were calculated and associated with corresponding citations. Relationship between
      distance of coauthors and citations for four author relationships (first-last,
      first-middle, last-middle, and middle-middle) were investigated at different
      spatial scales. At all sizes of collaborations (from two authors to dozens of
      authors), geographical proximity between first and last author is highly
      informative of impact at the microscale (i.e. within building) and beyond. The
      mean citation for first-last author relationship decreased as the distance
      between them increased in less than one km range as well as in the three
      categorized ranges (in the same building, same city, or different city). Such a
      trend was not seen in other three author relationships. CONCLUSIONS/SIGNIFICANCE:
      Despite the positive impact of emerging communication technologies on scientific
      research, our results provide striking evidence for the role of physical
      proximity as a predictor of the impact of collaborations.

PMID- 21179506
TI  - Matched sizes of activating and inhibitory receptor/ligand pairs are required for
      optimal signal integration by human natural killer cells.
AB  - It has been suggested that receptor-ligand complexes segregate or co-localise
      within immune synapses according to their size, and this is important for
      receptor signaling. Here, we set out to test the importance of receptor-ligand
      complex dimensions for immune surveillance of target cells by human Natural
      Killer (NK) cells. NK cell activation is regulated by integrating signals from
      activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1.
      Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell
      activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to
      inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting
      activation by normal-length MICA, only elongated HLA-C could inhibit activation
      by elongated MICA. Moreover, HLA-C and MICA that were matched in size co
      localised, whereas HLA-C and MICA that were different in size were segregated.
      These results demonstrate that receptor-ligand dimensions are important in NK
      cell recognition, and suggest that optimal integration of activating and
      inhibitory receptor signals requires the receptor-ligand complexes to have
      similar dimensions.

PMID- 21179508
TI  - Evidence of key tinnitus-related brain regions documented by a unique combination
      of manganese-enhanced MRI and acoustic startle reflex testing.
AB  - Animal models continue to improve our understanding of tinnitus pathogenesis and
      aid in development of new treatments. However, there are no diagnostic biomarkers
      for tinnitus-related pathophysiology for use in awake, freely moving animals. To
      address this disparity, two complementary methods were combined to examine
      reliable tinnitus models (rats repeatedly administered salicylate or exposed to a
      single noise event): inhibition of acoustic startle and manganese-enhanced MRI.
      Salicylate-induced tinnitus resulted in wide spread supernormal manganese uptake
      compared to noise-induced tinnitus. Neither model demonstrated significant
      differences in the auditory cortex. Only in the dorsal cortex of the inferior
      colliculus (DCIC) did both models exhibit supernormal uptake. Therefore, abnormal
      membrane depolarization in the DCIC appears to be important in tinnitus-mediated
      activity. Our results provide the foundation for future studies correlating the
      severity and longevity of tinnitus with hearing loss and neuronal activity in
      specific brain regions and tools for evaluating treatment efficacy across
      paradigms.

PMID- 21179509
TI  - Projecting global land-use change and its effect on ecosystem service provision
      and biodiversity with simple models.
AB  - BACKGROUND: As the global human population grows and its consumption patterns
      change, additional land will be needed for living space and agricultural
      production. A critical question facing global society is how to meet growing
      human demands for living space, food, fuel, and other materials while sustaining
      ecosystem services and biodiversity [1]. METHODOLOGY/PRINCIPAL FINDINGS: We
      spatially allocate two scenarios of 2000 to 2015 global areal change in urban
      land and cropland at the grid cell-level and measure the impact of this change on
      the provision of ecosystem services and biodiversity. The models and techniques
      used to spatially allocate land-use/land-cover (LULC) change and evaluate its
      impact on ecosystems are relatively simple and transparent [2]. The difference in
      the magnitude and pattern of cropland expansion across the two scenarios
      engenders different tradeoffs among crop production, provision of species
      habitat, and other important ecosystem services such as biomass carbon storage.
      For example, in one scenario, 5.2 grams of carbon stored in biomass is released
      for every additional calorie of crop produced across the globe; under the other
      scenario this tradeoff rate is 13.7. By comparing scenarios and their impacts we
      can begin to identify the global pattern of cropland and irrigation development
      that is significant enough to meet future food needs but has less of an impact on
      ecosystem service and habitat provision. CONCLUSIONS/SIGNIFICANCE: Urban area and
      croplands will expand in the future to meet human needs for living space,
      livelihoods, and food. In order to jointly provide desired levels of urban land,
      food production, and ecosystem service and species habitat provision the global
      society will have to become much more strategic in its allocation of intensively
      managed land uses. Here we illustrate a method for quickly and transparently
      evaluating the performance of potential global futures.

PMID- 21179510
TI  - Histidine domain-protein tyrosine phosphatase interacts with Grb2 and GrpL.
AB  - BACKGROUND: Histidine domain-protein tyrosine phosphatase (HD-PTP) plays a key
      role in vesicle trafficking and biogenesis. Although it is a large protein with
      at least five distinct structural domains, only a few of its interactors are
      presently known, and the significance of these interactions is largely obscure.
      METHODOLOGY AND RESULTS: In this study we performed a yeast two-hybrid screening
      using a human colon cDNA library and found that Grb2 and GrpL are binding
      partners of HD-PTP. Co-immunoprecipitation, pull-down and immunocytochemistry
      experiments confirmed the interactions. We also discovered that the central
      proline-rich and histidine-rich domain of HD-PTP is responsible for these
      interactions. SIGNIFICANCE: The interaction of HD-PTP with two adapters of the
      Grb2 family, essential for numerous signaling pathways, suggests that HD-PTP
      might be important for signaling through a plethora of receptors.

PMID- 21179511
TI  - A novel dimeric inhibitor targeting Beta2GPI in Beta2GPI/antibody complexes
      implicated in antiphospholipid syndrome.
AB  - BACKGROUND: beta2GPI is a major antigen for autoantibodies associated with
      antiphospholipid syndrome (APS), an autoimmune disease characterized by
      thrombosis and recurrent pregnancy loss. Only the dimeric form of beta2GPI
      generated by anti-beta2GPI antibodies is pathologically important, in contrast to
      monomeric beta2GPI which is abundant in plasma. PRINCIPAL FINDINGS: We created a
      dimeric inhibitor, A1-A1, to selectively target beta2GPI in beta2GPI/antibody
      complexes. To make this inhibitor, we isolated the first ligand-binding module
      from ApoER2 (A1) and connected two A1 modules with a flexible linker. A1-A1
      interferes with two pathologically important interactions in APS, the binding of
      beta2GPI/antibody complexes with anionic phospholipids and ApoER2. We compared
      the efficiency of A1-A1 to monomeric A1 for inhibition of the binding of
      beta2GPI/antibody complexes to anionic phospholipids. We tested the inhibition of
      beta2GPI present in human serum, beta2GPI purified from human plasma and the
      individual domain V of beta2GPI. We demonstrated that when beta2GPI/antibody
      complexes are formed, A1-A1 is much more effective than A1 in inhibition of the
      binding of beta2GPI to cardiolipin, regardless of the source of beta2GPI.
      Similarly, A1-A1 strongly inhibits the binding of dimerized domain V of beta2GPI
      to cardiolipin compared to the monomeric A1 inhibitor. In the absence of anti
      beta2GPI antibodies, both A1-A1 and A1 only weakly inhibit the binding of
      pathologically inactive monomeric beta2GPI to cardiolipin. CONCLUSIONS: Our
      results suggest that the approach of using a dimeric inhibitor to block beta2GPI
      in the pathological multivalent beta2GPI/antibody complexes holds significant
      promise. The novel inhibitor A1-A1 may be a starting point in the development of
      an effective therapeutic for antiphospholipid syndrome.

PMID- 21179512
TI  - Targeting and anchoring Tudor in the pole plasm of the Drosophila oocyte.
AB  - BACKGROUND: Germline formation is a highly regulated process in all organisms. In
      Drosophila embryos germ cells are specified by the pole plasm, a specialized
      cytoplasmic region containing polar granules. Components of these granules are
      also present in the perinuclear ring surrounding nurse cells, the nuage. Two such
      molecules are the Vasa and Tudor proteins. How Tudor localizes and is maintained
      in the pole plasm is, however, not known. METHODOLOGY/PRINCIPAL FINDINGS: Here,
      the process of Tudor localization in nuage and pole plasm was analyzed. The
      initial positioning of Tudor at the posterior pole of stage 9 oocytes was found
      to occur in the absence of a structurally detectable nuage. However, in mutants
      for genes encoding components of the nuage, including vasa, aubergine, maelstrom,
      and krimper, Tudor was detached from the posterior cortex in stage 10 oocytes,
      suggesting a prior passage in the nuage for its stability in the pole plasm.
      Further studies indicated that Valois, which was previously shown to bind in
      vitro to Tudor, mediates the localization of Tudor in the pole plasm by
      physically interacting with Oskar, the polar granule organizer. An association
      between Tudor and Vasa mediated by RNA was also detected in ovarian extracts.
      CONCLUSIONS/SIGNIFICANCE: The present data challenge the view that the assembly
      of the polar granules occurs in a stepwise and hierarchical manner and,
      consequently, a revised model of polar granule assembly is proposed. In this
      model Oskar recruits two downstream components of the polar granules, Vasa and
      Tudor, independently from each other: Vasa directly interacts with Oskar while
      Valois mediates the recruitment of Tudor by interacting with Oskar and Tudor.

PMID- 21179513
TI  - A new troodontid theropod dinosaur from the lower Cretaceous of Utah.
AB  - BACKGROUND: The theropod dinosaur family Troodontidae is known from the Upper
      Jurassic, Lower Cretaceous, and Upper Cretaceous of Asia and from the Upper
      Jurassic and Upper Cretaceous of North America. Before now no undisputed
      troodontids from North America have been reported from the Early Cretaceous.
      METHODOLOGY/PRINCIPAL FINDINGS: Herein we describe a theropod maxilla from the
      Lower Cretaceous Cedar Mountain Formation of Utah and perform a phylogenetic
      analysis to determine its phylogenetic position. The specimen is distinctive
      enough to assign to a new genus and species, Geminiraptor suarezarum.
      Phylogenetic analysis places G. suarezarum within Troodontidae in an unresolved
      polytomy with Mei, Byronosaurus, Sinornithoides, Sinusonasus, and
      Troodon+(Saurornithoides+Zanabazar). Geminiraptor suarezarum uniquely exhibits
      extreme pneumatic inflation of the maxilla internal to the antorbital fossa such
      that the anterior maxilla has a triangular cross-section. Unlike troodontids more
      closely related to Troodon, G. suarezarum exhibits bony septa between the dental
      alveoli and a promaxillary foramen that is visible in lateral view.
      CONCLUSIONS/SIGNIFICANCE: This is the first report of a North American troodontid
      from the Lower Cretaceous. It therefore contributes to a fuller understanding of
      troodontid biogeography through time. It also adds to the known dinosaurian fauna
      of the Cedar Mountain Formation.

PMID- 21179514
TI  - Does foraging behaviour affect female mate preferences and pair formation in
      captive zebra finches?
AB  - BACKGROUND: Successful foraging is essential for survival and reproductive
      success. In many bird species, foraging is a learned behaviour. To cope with
      environmental change and survive periods in which regular foods are scarce, the
      ability to solve novel foraging problems by learning new foraging techniques can
      be crucial. Although females have been shown to prefer more efficient foragers,
      the effect of males' foraging techniques on female mate choice has never been
      studied. We tested whether females would prefer males showing the same learned
      foraging technique as they had been exposed to as juveniles, or whether females
      would prefer males that showed a complementary foraging technique.
      METHODOLOGY/PRINCIPAL FINDINGS: We first trained juvenile male and female zebra
      finches (Taeniopygia guttata) to obtain a significant proportion of their food by
      one of two foraging techniques. We then tested whether females showed a
      preference for males with the same or the alternative technique. We found that
      neither a male's foraging technique nor his foraging performance affected the
      time females spent in his proximity in the mate-choice apparatus. We then
      released flocks of these finches into an aviary to investigate whether
      assortative pairing would be facilitated by birds taught the same technique
      exploiting the same habitat. Zebra finches trained as juveniles in a specific
      foraging technique maintained their foraging specialisation in the aviary as
      adults. However, pair formation and nest location were random with regard to
      foraging technique. CONCLUSIONS/SIGNIFICANCE: Our findings show that zebra
      finches can be successfully trained to be foraging specialists. However, the
      robust negative results of the conditions tested here suggest that learned
      foraging specializations do not affect mate choice or pair formation in our
      experimental context.

PMID- 21179515
TI  - Prescription drugs associated with reports of violence towards others.
AB  - CONTEXT: Violence towards others is a seldom-studied adverse drug event and an
      atypical one because the risk of injury extends to others. OBJECTIVE: To identify
      the primary suspects in adverse drug event reports describing thoughts or acts of
      violence towards others, and assess the strength of the association. METHODOLOGY:
      From the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS)
      data, we extracted all serious adverse event reports for drugs with 200 or more
      cases received from 2004 through September 2009. We identified any case report
      indicating homicide, homicidal ideation, physical assault, physical abuse or
      violence related symptoms. MAIN OUTCOME MEASURES: Disproportionality in reporting
      was defined as a) 5 or more violence case reports, b) at least twice the number
      of reports expected given the volume of overall reports for that drug, c) a chi2
      statistic indicating the violence cases were unlikely to have occurred by chance
      (p<0.01). RESULTS: We identified 1527 cases of violence disproportionally
      reported for 31 drugs. Primary suspect drugs included varenicline (an aid to
      smoking cessation), 11 antidepressants, 6 sedative/hypnotics and 3 drugs for
      attention deficit hyperactivity disorder. The evidence of an association was
      weaker and mixed for antipsychotic drugs and absent for all but 1
      anticonvulsant/mood stabilizer. Two or fewer violence cases were reported for
      435/484 (84.7%) of all evaluable drugs suggesting that an association with this
      adverse event is unlikely for these drugs. CONCLUSIONS: Acts of violence towards
      others are a genuine and serious adverse drug event associated with a relatively
      small group of drugs. Varenicline, which increases the availability of dopamine,
      and antidepressants with serotonergic effects were the most strongly and
      consistently implicated drugs. Prospective studies to evaluate systematically
      this side effect are needed to establish the incidence, confirm differences among
      drugs and identify additional common features.

PMID- 21179516
TI  - The comparison between circadian oscillators in mouse liver and pituitary gland
      reveals different integration of feeding and light schedules.
AB  - The mammalian circadian system is composed of multiple peripheral clocks that are
      synchronized by a central pacemaker in the suprachiasmatic nuclei of the
      hypothalamus. This system keeps track of the external world rhythms through
      entrainment by various time cues, such as the light-dark cycle and the feeding
      schedule. Alterations of photoperiod and meal time modulate the phase coupling
      between central and peripheral oscillators. In this study, we used real-time
      quantitative PCR to assess circadian clock gene expression in the liver and
      pituitary gland from mice raised under various photoperiods, or under a temporal
      restricted feeding protocol. Our results revealed unexpected differences between
      both organs. Whereas the liver oscillator always tracked meal time, the pituitary
      circadian clockwork showed an intermediate response, in between entrainment by
      the light regimen and the feeding-fasting rhythm. The same composite response was
      also observed in the pituitary gland from adrenalectomized mice under daytime
      restricted feeding, suggesting that circulating glucocorticoids do not inhibit
      full entrainment of the pituitary clockwork by meal time. Altogether our results
      reveal further aspects in the complexity of phase entrainment in the circadian
      system, and suggest that the pituitary may host oscillators able to integrate
      multiple time cues.

PMID- 21179517
TI  - Hospitalized children with 2009 pandemic influenza A (H1N1): comparison to
      seasonal influenza and risk factors for admission to the ICU.
AB  - BACKGROUND: Limited data are available describing the clinical presentation and
      risk factors for admission to the intensive care unit for children with 2009 H1N1
      infection. METHODS: We conducted a retrospective chart review of all hospitalized
      children with 2009 influenza A (H1N1) and 2008-09 seasonal influenza at The
      Children's Hospital, Denver, Colorado. RESULTS: Of the 307 children identified
      with 2009 H1N1 infections, the median age was 6 years, 61% were male, and 66% had
      underlying medical conditions. Eighty children (26%) were admitted to the ICU.
      Thirty-two (40%) of the ICU patients required intubation and 17 (53%) of the
      intubated patients developed acute respiratory distress syndrome (ARDS). Four
      patients required extracorporeal membrane oxygenation. Eight (3%) of the
      hospitalized children died. Admission to the ICU was significantly associated
      with older age and underlying neurological condition. Compared to the 90 children
      admitted during the 2008-09 season, children admitted with 2009 H1N1 influenza
      were significantly older, had a shorter length of hospitalization, more use of
      antivirals, and a higher incidence of ARDS. CONCLUSIONS: Compared to the 2008-09
      season, hospitalized children with 2009 H1N1 influenza were much older and had
      more severe respiratory disease. Among children hospitalized with 2009 H1N1
      influenza, risk factors for admission to the ICU included older age and having an
      underlying neurological condition. Children under the age of 2 hospitalized with
      2009 H1N1 influenza were significantly less likely to require ICU care compared
      to older hospitalized children.

PMID- 21179519
TI  - New microsatellite markers for examining genetic variation in peripheral and core
      populations of the Coastal Giant Salamander (Dicamptodon tenebrosus).
AB  - The Coastal Giant Salamander (Dicamptodon tenebrosus) is classified as threatened
      at the northern periphery of its range in British Columbia (BC), Canada,
      primarily due to forestry practices and habitat fragmentation. Characterising
      dispersal behaviour and population connectivity is therefore a priority for this
      region, while genetic differentiation in core versus peripheral locations remains
      unstudied in this wide-ranging species. We present seven new polymorphic
      microsatellite markers for use in population genetic analyses of D. tenebrosus.
      We examine locus characteristics and genetic variation in 12 streams at the
      species' northern range limit in BC, and within two regions representing sub
      peripheral (North Cascades) and core localities (South Cascades) in Washington
      State, United States. In BC, the number of alleles per locus ranged from 2-5 and
      observed heterozygosity ranged from 0.044-0.825. Genetic differentiation was
      highest between BC and the South Cascades, and intermediate between BC and the
      North Cascades. Across loci, mean allelic richness was similar across regions,
      while private allelic richness was highest in the core locality (corrected for
      sample size). These new microsatellite loci will be a valuable addition to
      existing markers for detailed landscape and population genetic analyses of D.
      tenebrosus across its range.

PMID- 21179518
TI  - Localization of mineralocorticoid receptors at mammalian synapses.
AB  - In the brain, membrane associated nongenomic steroid receptors can induce fast
      acting responses to ion conductance and second messenger systems of neurons.
      Emerging data suggest that membrane associated glucocorticoid and
      mineralocorticoid receptors may directly regulate synaptic excitability during
      times of stress when adrenal hormones are elevated. As the key neuron signaling
      interface, the synapse is involved in learning and memory, including traumatic
      memories during times of stress. The lateral amygdala is a key site for synaptic
      plasticity underlying conditioned fear, which can both trigger and be coincident
      with the stress response. A large body of electrophysiological data shows rapid
      regulation of neuronal excitability by steroid hormone receptors. Despite the
      importance of these receptors, to date, only the glucocorticoid receptor has been
      anatomically localized to the membrane. We investigated the subcellular sites of
      mineralocorticoid receptors in the lateral amygdala of the Sprague-Dawley rat.
      Immunoblot analysis revealed the presence of mineralocorticoid receptors in the
      amygdala. Using electron microscopy, we found mineralocorticoid receptors
      expressed at both nuclear including: glutamatergic and GABAergic neurons and
      extra nuclear sites including: presynaptic terminals, neuronal dendrites, and
      dendritic spines. Importantly we also observed mineralocorticoid receptors at
      postsynaptic membrane densities of excitatory synapses. These data provide direct
      anatomical evidence supporting the concept that, at some synapses, synaptic
      transmission is regulated by mineralocorticoid receptors. Thus part of the stress
      signaling response in the brain is a direct modulation of the synapse itself by
      adrenal steroids.

PMID- 21179520
TI  - Regulation and functions of the lms homeobox gene during development of embryonic
      lateral transverse muscles and direct flight muscles in Drosophila.
AB  - BACKGROUND: Patterning and differentiation of developing musculatures require
      elaborate networks of transcriptional regulation. In Drosophila, significant
      progress has been made into identifying the regulators of muscle development and
      defining their interactive networks. One major family of transcription factors
      involved in these processes consists of homeodomain proteins. In flies, several
      members of this family serve as muscle identity genes to specify the fates of
      individual muscles, or groups thereof, during embryonic and/or adult muscle
      development. Herein, we report on the expression and function of a new Drosophila
      homeobox gene during both embryonic and adult muscle development.
      METHODOLOGY/PRINCIPAL FINDINGS: The newly described homeobox gene, termed lateral
      muscles scarcer (lms), which has yet uncharacterized orthologs in other
      invertebrates and primitive chordates but not in vertebrates, is expressed
      exclusively in subsets of developing muscle tissues. In embryos, lms is expressed
      specifically in the four lateral transverse (LT) muscles and their founder cells
      in each hemisegment, whereas in larval wing imaginal discs, it is expressed in
      myoblasts that develop into direct flight muscles (DFMs), which are important for
      proper wing positioning. We have analyzed the regulatory inputs of various other
      muscle identity genes with overlapping or complementary expression patterns
      towards the cell type specific regulation of lms expression. Further we
      demonstrate that lms null mutants exhibit reduced numbers of embryonic LT
      muscles, and null mutant adults feature held-out-wing phenotypes. We provide a
      detailed description of the pattern and morphology of the direct flight muscles
      in the wild type and lms mutant flies by using the recently-developed
      ultramicroscopy and show that, in the mutants, all DFMs are present and present
      normal morphologies. CONCLUSIONS/SIGNIFICANCE: We have identified the homeobox
      gene lms as a new muscle identity gene and show that it interacts with various
      previously-characterized muscle identity genes to regulate normal formation of
      embryonic lateral transverse muscles. In addition, the direct flight muscles in
      the adults require lms for reliably exerting their functions in controlling wing
      postures.

PMID- 21179521
TI  - Dogs' expectation about signalers' body size by virtue of their growls.
AB  - Several studies suggest that dogs, as well as primates, utilize a mental
      representation of the signaler after hearing its vocalization and can match this
      representation with other features provided by the visual modality. Recently it
      was found that a dogs' growl is context specific and contains information about
      the caller's body size. Whether dogs can use the encoded information is as yet
      unclear. In this experiment, we tested whether dogs can assess the size of
      another dog if they hear an agonistic growl paired with simultaneous video
      projection of two dog pictures. One of them matched the size of the growling dog,
      while the other one was either 30% larger or smaller. In control groups, noise,
      cat pictures or projections of geometric shapes (triangles) were used. The
      results showed that dogs look sooner and longer at the dog picture matching the
      size of the caller. No such preference was found with any of the control stimuli,
      suggesting that dogs have a mental representation of the caller when hearing its
      vocalization.

PMID- 21179522
TI  - The TonB dimeric crystal structures do not exist in vivo.
AB  - The TonB system energizes transport of nutrients across the outer membrane of
      Escherichia coli using cytoplasmic membrane proton motive force (PMF) for energy.
      Integral cytoplasmic membrane proteins ExbB and ExbD appear to harvest PMF and
      transduce it to TonB. The carboxy terminus of TonB then physically interacts with
      outer membrane transporters to allow translocation of ligands into the
      periplasmic space. The structure of the TonB carboxy terminus (residues ~150 to
      239) has been solved several times with similar results. Our previous results
      hinted that in vitro structures might not mimic the dimeric conformations that
      characterize TonB in vivo. To test structural predictions and to identify
      irreplaceable residues, the entire carboxy terminus of TonB was scanned with Cys
      substitutions. TonB I232C and N233C, predicted to efficiently form disulfide
      linked dimers in the crystal structures, did not do so. In contrast, Cys
      substitutions positioned at large distances from one another in the crystal
      structures efficiently formed dimers. Cys scanning identified seven functionally
      important residues. However, no single residue was irreplaceable. The phenotypes
      conferred by changes of the seven residues depended on both the specific assay
      used and the residue substituted. All seven residues were synergistic with one
      another. The buried nature of the residues in the structures was also
      inconsistent with these properties. Taken together, these results indicate that
      the solved dimeric crystal structures of TonB do not exist. The most likely
      explanation for the aberrant structures is that they were obtained in the absence
      of the TonB transmembrane domain, ExbB, ExbD, and/or the PMF.

PMID- 21179523
TI  - Fixed-dose Sumatriptan/Naproxen Sodium Compared with each Monotherapy Utilizing
      the Novel Composite Endpoint of Sustained Pain-free/no Adverse Events.
AB  - A novel composite endpoint, sustained pain-free/no adverse events, was recently
      proposed as a more rigorous means of capturing in a single measure the attributes
      of migraine pharmacotherapy that patients consider most important: rapid and
      sustained pain-free response with no side-effects. Using pooled data from two
      replicate randomized, double-blind, parallel-group, placebo-controlled studies,
      this post hoc analysis compared the fixed-dose combination tablet
      sumatriptan/naproxen sodium (n = 726) with sumatriptan monotherapy (n = 723),
      naproxen sodium monotherapy (n = 720), and placebo (n = 742) with respect to
      sustained pain-free/no adverse events and closely related composite measures.
      Sustained pain-free/no adverse events was defined as having both a sustained pain
      free response from 2 through 24 hours post-dose with no use of rescue medication
      and having no adverse events within up to 5 days after dosing with study
      medication. The percentage of patients with sustained pain-free/no adverse events
      was 16% with sumatriptan/naproxen sodium compared with 11%, 9% and 7% for
      sumatriptan, naproxen sodium and placebo, respectively (p<0.01
      sumatriptan/naproxen sodium versus each other treatment). Sumatriptan/naproxen
      sodium was also significantly more effective than sumatriptan, naproxen sodium,
      and placebo for other composite endpoints including the percentages of patients
      with (1) sustained pain-free/no adverse events within 1 day; (2) sustained pain
      free/no drug-related adverse events within up to 5 days; (3) sustained pain
      free/no drug-related adverse events within 1 day; (4) sustained pain relief/no
      adverse events within up to 5 days; and (5) sustained pain relief/no adverse
      events within 1 day. The results demonstrate the superiority of
      sumatriptan/naproxen sodium to sumatriptan monotherapy, naproxen sodium
      monotherapy and placebo with respect to the rigorous and clinically relevant
      endpoint of sustained pain-free/no adverse events and reinforce the usefulness of
      utilizing this new composite endpoint.

PMID- 21179524
TI  - Progress in Enzyme Replacement Therapy in Glycogen Storage Disease Type II.
AB  - Glycogen storage disease type II (GSDII) is an autosomal recessive lysosomal
      disorder caused by mutations in the gene encoding alpha-glucosidase (GAA). The
      disease can be clinically classified into three types: a severe infantile form, a
      juvenile and an adultonset form. Cases with juvenile or adult onset GSDII mimic
      limb-girdle muscular dystrophy or polymyositis and are often characterized by
      respiratory involvement. GSDII patients are diagnosed by biochemical assay and by
      molecular characterization of the GAA gene. Ascertaining a natural history of
      patients with heterogeneous late-onset GSDII is useful for evaluating their
      progressive functional disability. A significant decline is observed over the
      years in skeletal and respiratory muscle function. Enzyme replacement therapy
      (ERT) has provided encouraging results in the infantile form. It is not yet known
      if ERT is effective in late-onset GSDII. We examined a series of 11 patients
      before and after ERT evaluating muscle strength by MRC, timed and graded
      functional tests, 6-minute walk test (6MWT), respiratory function by spirometric
      parameters and quality of life. We observed a partial improvement during a
      prolonged follow-up from 3 to 18 months. The use of different clinical parameters
      in the proposed protocol seems crucial to determine the efficacy of ERT, since
      not all late-onset patients respond similarly to ERT.

PMID- 21179525
TI  - Drug and Nondrug Treatment in Tension-type Headache.
AB  - Tension-type headache (TTH) is a common primary headache with tremendous
      socioeconomic impact. Establishment of an accurate diagnosis is important before
      initiation of any treatment. Nondrug management is crucial. Information,
      reassurance and identification of trigger factors may be rewarding. Psychological
      treatments with scientific evidence for efficacy include relaxation training, EMG
      biofeedback and cognitive-behavioural therapy. Physical therapy and acupuncture
      are widely used, but the scientific evidence for efficacy is sparse. Simple
      analgesics are the mainstays for treatment of episodic TTH. Combination
      analgesics, triptans, muscle relaxants and opioids should not be used, and it is
      crucial to avoid frequent and excessive use of simple analgesics to prevent the
      development of medication-overuse headache. The tricyclic antidepressant
      amitriptyline is drug of first choice for the prophylactic treatment of chronic
      TTH. The efficacy is modest and treatment is often hampered by side effects.
      Thus, treatment of frequent TTH is often difficult and multidisciplinary
      treatment strategies can be useful. The development of specific
      nonpharmacological and pharmacological managements for TTH with higher efficacy
      and fewer side effects is urgently needed. Future studies should also examine the
      relative efficacy of the various treatment modalities; for example,
      psychological, physical and pharmacological treatments, and clarify how treatment
      programs should be optimized to best suit the individual patient.

PMID- 21179527
TI  - Comparing drug treatments in epilepsy.
AB  - The great majority of randomised controlled trials (RCTs) that compare
      antiepileptic drugs are industry sponsored and have the objective of obtaining a
      monotherapy license for a drug. Such trials do not inform everyday clinical
      practice as they tend to be too short and to depart from clinical practice by
      restricting clinicians in their choice of actions. The data that exists provides
      evidence that drugs with actions on voltage-gated sodium channels provide best
      seizure control for localised onset seizures and epilepsy syndromes, while
      valproate provides best seizure control for generalised epilepsy and unclassified
      syndromes. Drugs do, however, vary in their tolerability over the short term and
      in their risk for rare serious idiosyncratic adverse events, chronic toxicity and
      teratogenicity; issues that cannot be examined within the scope of RCTs.

PMID- 21179526
TI  - Therapy for Alzheimer's Disease: How Effective are Current Treatments?
AB  - Available symptomatic therapies for the treatment of Alzheimer's disease (AD)
      have been based on known neurotransmitter dysfunctions associated with the
      illness. The second-generation cholinesterase inhibitors and the N-methyl D
      aspartate receptor antagonist memantine have been widely prescribed and studied.
      Meta-analyses of these therapies were reviewed, focusing on effectiveness and
      tolerability. Although many of the meta-analyses demonstrate statistically
      significant improvements, some question if these benefits are sufficient to
      justify their current widespread and protracted use. This has spurred the
      development of new disease-modifying therapies that aim to have a greater impact
      on this debilitating illness.

PMID- 21179528
TI  - Monoclonal antibodies in multiple sclerosis treatment: current and future steps.

PMID- 21179529
TI  - The 39-Item Parkinson's Disease Questionnaire (PDQ-39): Is it a Unidimensional
      Construct?
AB  - The 39-item Parkinson's Disease Questionnaire, and particularly its summary index
      (PDQ-39SI) is a widely used patient-reported clinical trial endpoint. A basic
      assumption when summing items into a total score is that they represent a common
      variable. We therefore assessed the unidimensionality of the PDQ-39SI using Rasch
      and confirmatory factor analysis. Both analyses showed model misfit. Adjustment
      for differential item functioning and disordered response category thresholds did
      not improve model fit, and residual analyses showed deviation from
      unidimensionality. These data indicate multidimensionality and challenge the
      interpretation and validity of PDQ-39SI scores. Clinicians and investigators
      should use and interpret the PDQ-39SI with caution.

PMID- 21179530
TI  - Diagnosis and management of essential tremor and dystonic tremor.
AB  - Essential tremor (ET) is the most common adult movement disorder. Traditionally
      considered as a benign disease, it can cause an important physical and
      psychosocial disability. Drug treatment for ET remains poor and often
      unsatisfactory. Current therapeutic strategies for ET are reviewed according to
      the level of discomfort caused by tremor. For mild tremor, nonpharmacological
      strategies consist of alcohol and acute pharmacological therapy; for moderate
      tremor, pharmacological therapies (propranolol, gabapentin, primidone,
      topiramate, alprazolam and other drugs); and for severe tremor, the role of
      functional surgery is emphasised (thalamic deep brain stimulation, thalamotomy).
      The more specific treatment of head tremor with the use of botulinum toxin is
      also discussed. Several points are discussed to guide the immediate research into
      this disease in the near future. Dystonic tremor is a common symptom in dystonia.
      Diagnostic criteria for dystonic tremor and differential diagnosis with
      psychogenic tremor and ET are described. Treatment of dystonic tremor matches the
      treatment of dystonia. In cases of symptomatic dystonic tremor similar to ET,
      therapeutic strategies would be the same as for ET.

PMID- 21179531
TI  - Current treatment of vestibular, ocular motor disorders and nystagmus.
AB  - Vertigo and dizziness are among the most common complaints with a lifetime
      prevalence of about 30%. The various forms of vestibular disorders can be treated
      with pharmacological therapy, physical therapy, psychotherapeutic measures or,
      rarely, surgery. In this review, the current pharmacological treatment options
      for peripheral and central vestibular, cerebellar and ocular motor disorders will
      be described. They are as follows for peripheral vestibular disorders. In
      vestibular neuritis recovery of the peripheral vestibular function can be
      improved by treatment with oral corticosteroids. In Meniere's disease a recent
      study showed long-term high-dose treatment with betahistine has a significant
      effect on the frequency of the attacks. The use of aminopyridines introduced a
      new therapeutic principle in the treatment of downbeat and upbeat nystagmus and
      episodic ataxia type 2 (EA 2). These potassium channel blockers presumably
      increase the activity and excitability of cerebellar Purkinje cells, thereby
      augmenting the inhibitory influence of these cells on vestibular and cerebellar
      nuclei. A few studies showed that baclofen improves periodic alternating
      nystagmus, and gabapentin and memantine, pendular nystagmus. However, many other
      eye movement disorders such as ocular flutter opsoclonus, central positioning, or
      see-saw nystagmus are still difficult to treat. Although progress has been made
      in the treatment of vestibular neuritis, downbeat and upbeat nystagmus, as well
      as EA 2, state-of-the-art trials must still be performed on many vestibular and
      ocular motor disorders, namely Meniere's disease, bilateral vestibular failure,
      vestibular paroxysmia, vestibular migraine, and many forms of central eye
      movement disorders.

PMID- 21179532
TI  - Blood pressure and dementia - a comprehensive review.
AB  - Alzheimer's disease (AD) and vascular dementia (VaD) are important causes of
      cognitive decline in the elderly. As a result of an ageing population worldwide,
      the incidence of dementia is expected to rise exponentially over the coming
      decades. Vascular risk factors are implicated in the pathogenesis of both AD and
      VaD. Hypertension in midlife is particularly associated with an increased risk of
      developing dementia. One might hope the treatment of high blood pressure in
      midlife would reduce the risk of developing dementia, as it does the risk of
      stroke. Divergent results have been reported in studies examining this effect,
      with the evidence suggesting that certain antihypertensives confer benefits
      beyond others. This implies that certain drugs may have neuroprotective
      properties separate to their blood pressure lowering capabilities. Recent trials
      have added to our understanding of these relationships.

PMID- 21179534
TI  - Genetic variants in toll-like receptors are not associated with rheumatoid
      arthritis susceptibility or anti-tumour necrosis factor treatment outcome.
AB  - BACKGROUND: Several studies point to a role of Toll-like receptors (TLRs) in the
      development of rheumatoid arthritis (RA). We investigated if genetic variants in
      TLR genes are associated with RA and response to tumour necrosis factor blocking
      (anti-TNF) medication. METHODOLOGY AND PRINCIPAL FINDINGS: 22 single nucleotide
      polymorphisms (SNPs) in seven TLR genes were genotyped in a Dutch cohort
      consisting of 378 RA patients and 294 controls. Significantly associated variants
      were investigated in replication cohorts from The Netherlands, United Kingdom and
      Sweden (2877 RA patients and 2025 controls). 182 of the Dutch patients were
      treated with anti-TNF medication. Using these patients and a replication cohort
      (269 Swedish patients) we analysed if genetic variants in TLR genes were
      associated with anti-TNF outcome. In the discovery phase of the study we found a
      significant association of SNPs rs2072493 in TLR5 and rs3853839 in TLR7 with RA
      disease susceptibility. Meta-analysis of discovery and replication cohorts did
      not confirm these findings. SNP rs2072493 in TLR5 was associated with anti-TNF
      outcome in the Dutch but not in the Swedish population. CONCLUSION: We conclude
      that genetic variants in TLRs do not play a major role in susceptibility for
      developing RA nor in anti-TNF treatment outcome in a Caucasian population.

PMID- 21179533
TI  - Pathogenesis and treatment of immune-mediated neuropathies.
AB  - Immune-mediated neuropathies represent a heterogeneous spectrum of peripheral
      nerve disorders that can be classified according to time course, predominant
      involvement of motor/sensory fibers, distribution of deficits and paraclinical
      parameters such as electrophysiology and serum antibodies. In the last few years,
      significant advances have been achieved in elucidating underlying
      pathomechanisms, which made it possible to identify potential therapeutic
      targets. In this review, we discuss the latest development in pathogenesis and
      treatment of immune-mediated neuropathies.

PMID- 21179535
TI  - Inhibition of the nuclear import of cubitus interruptus by roadkill in the
      presence of strong hedgehog signal.
AB  - Hedgehog (Hh) signalling plays an important role in various developmental
      processes by activating the Cubitus interruptus (Ci)/Glioblastoma (Gli) family of
      transcription factors. In the process of proper pattern formation, Ci activity is
      regulated by multiple mechanisms, including processing, trafficking, and
      degradation. However, it remains elusive how Ci distinctly recognizes the strong
      and moderate Hh signals. Roadkill (Rdx) induces Ci degradation in the anterior
      region of the Drosophila wing disc. Here, we report that Rdx inhibited Ci
      activity by two different mechanisms. In the region abutting the
      anterior/posterior boundary, which receives strong Hh signal, Rdx inhibited the
      nuclear import of Ci by releasing importin alpha3 from Ci. In this region, Rdx
      negatively regulated the expression of transcription factor Knot/Collier. In
      farther anterior regions receiving moderate levels of Hh signal, Rdx induced Ci
      degradation, as reported previously. Thus, two different mechanisms by which Rdx
      negatively regulates Ci may play an important role in the fine-tuning of Hh
      responses.

PMID- 21179536
TI  - An alternate method of classifying allergic bronchopulmonary aspergillosis based
      on high-attenuation mucus.
AB  - BACKGROUND AND AIM: Allergic bronchopulmonary aspergillosis (ABPA) is classified
      radiologically based on the findings of central bronchiectasis (CB) and other
      radiologic features (ORF). However, the long-term clinical significance of these
      classifications remains unknown. We hypothesized that the immunological activity
      and outcomes of ABPA could be predicted on HRCT chest finding of high-attenuation
      mucus (HAM), a marker of inflammatory activity. In this study, we evaluate the
      severity and clinical outcomes of ABPA with different radiological
      classifications. METHODS: PATIENTS WERE CLASSIFIED BASED ON CT CHEST FINDINGS AS:
      (a) serologic ABPA (ABPA-S) and ABPA-CB; (b) ABPA-S, ABPA-CB, and ABPA-CB-ORF;
      and, (c) ABPA-S, ABPA-CB and ABPA-CB-HAM. The clinical, spirometric and
      serological (total and A fumigatus specific IgE levels, eosinophil count)
      severity of the disease and clinical outcomes in various classifications were
      analyzed. RESULTS: Of the 234 (123 males, 111 females; mean age, 34.1 years)
      patients, 55 (23.5%) had normal HRCT, 179 (76.5%) had CB, 49 (20.9%) had HAM, and
      27 (11.5%) had ORF. All immunological markers were consistently higher in the HAM
      classification, while in other classifications these findings were inconsistent.
      On multivariate analysis, the factors predicting frequent relapses were presence
      of HAM (OR 7.38; 95% CI, 3.21-17.0) and CB (OR 3.93; 95% CI, 1.63-9.48) after
      adjusting for ORF. CONCLUSIONS: The classification scheme based on HAM most
      consistently predicts immunological severity in ABPA. Central bronchiectasis and
      HAM are independent predictors of recurrent relapses in ABPA. Hence, HAM should
      be employed in the radiological classification of ABPA.

PMID- 21179537
TI  - Evolution of an agriculture-associated disease causing Campylobacter coli clade:
      evidence from national surveillance data in Scotland.
AB  - The common zoonotic pathogen Campylobacter coli is an important cause of
      bacterial gastroenteritis worldwide but its evolution is incompletely understood.
      Using multilocus sequence type (MLST) data of 7 housekeeping genes from a
      national survey of Campylobacter in Scotland (2005/6), and a combined population
      genetic-phylogenetics approach, we investigated the evolutionary history of C.
      coli. Genealogical reconstruction of isolates from clinical infection, farm
      animals and the environment, revealed a three-clade genetic structure. The
      majority of farm animal, and all disease causing genotypes belonged to a single
      clade (clade 1) which had comparatively low synonymous sequence diversity, little
      deep branching genetic structure, and a higher number of shared alleles providing
      evidence of recent clonal decent. Calibration of the rate of molecular evolution,
      based on within-species genetic variation, estimated a more rapid rate of
      evolution than in traditional estimates. This placed the divergence of the clades
      at less than 2500 years ago, consistent with the introduction of an agricultural
      niche having had an effect upon the evolution of the C. coli clades. Attribution
      of clinical isolate genotypes to source, using an asymmetric island model,
      confirmed that strains from chicken and ruminants, and not pigs or turkeys, are
      the principal source of human C. coli infection. Taken together these analyses
      are consistent with an evolutionary scenario describing the emergence of
      agriculture-associated C. coli lineage that is an important human pathogen.

PMID- 21179538
TI  - Engineering the chloroplast targeted malarial vaccine antigens in Chlamydomonas
      starch granules.
AB  - BACKGROUND: Malaria, an Anopheles-borne parasitic disease, remains a major global
      health problem causing illness and death that disproportionately affects
      developing countries. Despite the incidence of malaria, which remains one of the
      most severe infections of human populations, there is no licensed vaccine against
      this life-threatening disease. In this context, we decided to explore the
      expression of Plasmodium vaccine antigens fused to the granule bound starch
      synthase (GBSS), the major protein associated to the starch matrix in all starch
      accumulating plants and algae such as Chlamydomonas reinhardtii. METHODS AND
      FINDINGS: We describe the development of genetically engineered starch granules
      containing plasmodial vaccine candidate antigens produced in the unicellular
      green algae Chlamydomonas reinhardtii. We show that the C-terminal domains of
      proteins from the rodent Plasmodium species, Plasmodium berghei Apical Major
      Antigen AMA1, or Major Surface Protein MSP1 fused to the algal granule bound
      starch synthase (GBSS) are efficiently expressed and bound to the polysaccharide
      matrix. Mice were either immunized intraperitoneally with the engineered starch
      particles and Freund adjuvant, or fed with the engineered particles co-delivered
      with the mucosal adjuvant, and challenged intraperitoneally with a lethal
      inoculum of P. Berghei. Both experimental strategies led to a significantly
      reduced parasitemia with an extension of life span including complete cure for
      intraperitoneal delivery as assessed by negative blood thin smears. In the case
      of the starch bound P. falciparum GBSS-MSP1 fusion protein, the immune sera or
      purified immunoglobulin G of mice immunized with the corresponding starch
      strongly inhibited in vitro the intra-erythrocytic asexual development of the
      most human deadly plasmodial species. CONCLUSION: This novel system paves the way
      for the production of clinically relevant plasmodial antigens as algal starch
      based particles designated herein as amylosomes, demonstrating that efficient
      production of edible vaccines can be genetically produced in Chlamydomonas.

PMID- 21179539
TI  - Listeria monocytogenes infection affects a subset of Ly49-expressing NK cells in
      the rat.
AB  - NK cells are protective against certain bacterial and viral infections, and their
      production of IFN-gamma is important for the early innate immune defence against
      L. monocytogenes. We have previously shown that depletion of NK cells in rats
      leads to increased bacterial burden upon L. monocytogenes infection, and that a
      subset of NK cells encompassing the majority of Ly49 receptors (Ly49s3+ NK cells)
      contributed to this effect. In this study, we have further investigated how the
      Ly49s3+ NK cell subset is affected by L. monocytogenes infection. We observed an
      increased percentage of Ly49s3+ NK cells in the spleen and a reduction in the
      bone marrow within the first 48 hrs of L. monocytogenes infection. Concomitantly,
      we observed increased expression levels of the inflammatory chemokine receptors
      CCR5 and CXCR3 by Ly49s3+ bone marrow NK cells, as compared to Ly49s3- NK cells,
      suggesting involvement of Ly49s3+ NK cells in the early phase of infection.
      However, NK cell production of IFN-gamma was independent of Ly49 receptor
      expression. Furthermore, we observed increased expression levels of MHC class I
      molecules on both macrophages and NK cells during the first 48 hrs of infection,
      paralleled by a reduction in the surface expression of Ly49s3 on NK cells. In
      conclusion, L. monocytogenes infection modulates the tissue distribution of
      Ly49s3+ NK cells, and induces increased MHC class I expression and hence reduced
      surface expression of Ly49 receptors on NK cells. These changes indicate that L.
      monocytogenes infection may have multiple effects on NK cells in vivo, and
      suggests the involvement of Ly49-expressing NK cells in the immune responses
      towards L. monocytogenes.

PMID- 21179540
TI  - High diversity of the fungal community structure in naturally-occurring
      Ophiocordyceps sinensis.
AB  - BACKGROUND: Ophiocordyceps sinensis (syn. Cordyceps sinensis), which is a
      parasite of caterpillars and is endemic to alpine regions on the Tibetan Plateau,
      is one of the most valuable medicinal fungi in the world. "Natural O. sinensis
      specimens" harbor various other fungi. Several of these other fungi that have
      been isolated from natural O. sinensis specimens have similar chemical components
      and/or pharmaceutical effects as O. sinensis. Nevertheless, the mycobiota of
      natural O. sinensis specimens has not been investigated in detail.
      METHODOLOGY/PRINCIPAL FINDINGS: Based on the technique of PCR-single-strand
      conformation polymorphism (PCR-SSCP), the mycobiota of three different sections
      (stromata, sclerotia, and mycelial cortices) from natural O. sinensis specimens
      were investigated using both culture-dependent and -independent methods. For the
      culture-dependent method, 572 fungal strains were isolated, and 92 putative
      operational taxonomic units (OTUs) were identified from 226 sequenced strains
      with the threshold of 97%. For the culture-independent method, 490 fungal clones
      were identified from about 3000 clones of ITS fragments from the whole-community
      DNA; based on PCR-SSCP analyses, 266 of these clones were selected to be
      sequenced, and 118 putative OTUs were detected. The overwhelming majority of
      isolates/clones and OTUs were detected from mycelial cortices; only a few were
      detected from stromata and sclerotia. The most common OTUs detected with both
      methods belonged to Ascomycota; however, only 13 OTUs were detected
      simultaneously by both methods. Potential novel lineages were detected by each of
      the two methods. CONCLUSIONS/SIGNIFICANCE: A great number of fungal species
      present in the mycobiota of naturally-occurring O. sinensis specimens were
      detected, and many of them may represent undescribed lineages. That only a few of
      the same OTUs were detected by both methods indicated that different methods
      should be used. This study increased our understanding about the fungal community
      structure of this valuable medicinal herb.

PMID- 21179541
TI  - Both geography and ecology contribute to mating isolation in guppies.
AB  - Local adaptation to different environments can promote mating isolation--either
      as an incidental by-product of trait divergence, or as a result of selection to
      avoid maladaptive mating. Numerous recent empirical examples point to the common
      influence of divergent natural selection on speciation based largely on evidence
      of strong pre-mating isolation between populations from different habitat types.
      Accumulating evidence for natural selection's influence on speciation is
      therefore no longer a challenge. The difficulty, rather, is in determining the
      mechanisms involved in the progress of adaptive divergence to speciation once
      barriers to gene flow are already present. Here, we present results of both
      laboratory and field experiments with Trinidadian guppies (Poecilia reticulata)
      from different environments, who do not show complete reproductive isolation
      despite adaptive divergence. We investigate patterns of mating isolation between
      populations that do and do not exchange migrants and show evidence for both by
      product and reinforcement mechanisms depending on female ecology. Specifically,
      low-predation females discriminate against all high-predation males thus implying
      a by-product mechanism, whereas high-predation females only discriminate against
      low-predation males from further upstream in the same river, implying selection
      to avoid maladaptive mating. Our study thus confirms that mechanisms of adaptive
      speciation are not necessarily mutually exclusive and uncovers the complex
      ecology-geography interactions that underlie the evolution of mating isolation in
      nature.

PMID- 21179542
TI  - Genetic evidence highlights potential impacts of by-catch to cetaceans.
AB  - Incidental entanglement in fishing gear is arguably the most serious threat to
      many populations of small cetaceans, judging by the alarming number of captured
      animals. However, other aspects of this threat, such as the potential capture of
      mother-offspring pairs or reproductive pairs, could be equally or even more
      significant but have rarely been evaluated. Using a combination of demographic
      and genetic data we provide evidence that i) Franciscana dolphin pairs that are
      potentially reproductive and mother-offspring pairs form temporal bonds, and ii)
      are entangled simultaneously. Our results highlight potential demographic and
      genetic impacts of by-catch to cetacean populations: the joint entanglement of
      mother-offspring or reproductive pairs, compared to random individuals, might
      exacerbate the demographic consequences of by-catch, and the loss of groups of
      relatives means that significant components of genetic diversity could be lost
      together. Given the social nature of many odontocetes (toothed cetaceans), we
      suggest that these potential impacts could be rather general to the group and
      therefore by-catch could be more detrimental than previously considered.

PMID- 21179543
TI  - Decreased exploratory activity in a mouse model of 15q duplication syndrome;
      implications for disturbance of serotonin signaling.
AB  - Autism spectrum disorders (ASDs) have garnered significant attention as an
      important grouping of developmental brain disorders. Recent genomic studies have
      revealed that inherited or de novo copy number variations (CNVs) are
      significantly involved in the pathophysiology of ASDs. In a previous report from
      our laboratory, we generated mice with CNVs as a model of ASDs, with a duplicated
      mouse chromosome 7C that is orthologous to human chromosome 15q11-13. Behavioral
      analyses revealed paternally duplicated (patDp/+) mice displayed abnormal
      behaviors resembling the symptoms of ASDs. In the present study, we extended
      these findings by performing various behavioral tests with C57BL/6J patDp/+ mice,
      and comprehensively measuring brain monoamine levels with ex vivo high
      performance liquid chromatography. Compared with wild-type controls, patDp/+ mice
      exhibited decreased locomotor and exploratory activities in the open field test,
      Y-maze test, and fear-conditioning test. Furthermore, their decreased activity
      levels overcame increased appetite induced by 24 hours of food deprivation in the
      novelty suppressed feeding test. Serotonin levels in several brain regions of
      adult patDp/+ mice were lower than those of wild-type control, with no concurrent
      changes in brain levels of dopamine or norepinephrine. Moreover, analysis of
      monoamines in postnatal developmental stages demonstrated reduced brain levels of
      serotonin in young patDp/+ mice. These findings suggest that a disrupted brain
      serotonergic system, especially during postnatal development, may generate the
      phenotypes of patDp/+ mice.

PMID- 21179544
TI  - Proteochemometric modeling of the susceptibility of mutated variants of the HIV-1
      virus to reverse transcriptase inhibitors.
AB  - BACKGROUND: Reverse transcriptase is a major drug target in highly active
      antiretroviral therapy (HAART) against HIV, which typically comprises two
      nucleoside/nucleotide analog reverse transcriptase (RT) inhibitors (NRTIs) in
      combination with a non-nucleoside RT inhibitor or a protease inhibitor.
      Unfortunately, HIV is capable of escaping the therapy by mutating into drug
      resistant variants. Computational models that correlate HIV drug susceptibilities
      to the virus genotype and to drug molecular properties might facilitate selection
      of improved combination treatment regimens. METHODOLOGY/PRINCIPAL FINDINGS: We
      applied our earlier developed proteochemometric modeling technology to analyze
      HIV mutant susceptibility to the eight clinically approved NRTIs. The data set
      used covered 728 virus variants genotyped for 240 sequence residues of the DNA
      polymerase domain of the RT; 165 of these residues contained mutations; totally
      the data-set covered susceptibility data for 4,495 inhibitor-RT combinations.
      Inhibitors and RT sequences were represented numerically by 3D-structural and
      physicochemical property descriptors, respectively. The two sets of descriptors
      and their derived cross-terms were correlated to the susceptibility data by
      partial least-squares projections to latent structures. The model identified more
      than ten frequently occurring mutations, each conferring more than two-fold loss
      of susceptibility for one or several NRTIs. The most deleterious mutations were
      K65R, Q151M, M184V/I, and T215Y/F, each of them decreasing susceptibility to most
      of the NRTIs. The predictive ability of the model was estimated by cross
      validation and by external predictions for new HIV variants; both procedures
      showed very high correlation between the predicted and actual susceptibility
      values (Q2=0.89 and Q2ext=0.86). The model is available at www.hivdrc.org as a
      free web service for the prediction of the susceptibility to any of the
      clinically used NRTIs for any HIV-1 mutant variant. CONCLUSIONS/SIGNIFICANCE: Our
      results give directions how to develop approaches for selection of genome-based
      optimum combination therapy for patients harboring mutated HIV variants.

PMID- 21179545
TI  - GSK3 regulates mitotic chromosomal alignment through CRMP4.
AB  - BACKGROUND: Glycogen Synthase Kinase 3 (GSK3) has been implicated in regulating
      chromosomal alignment and mitotic progression but the physiological substrates
      mediating these GSK3-dependent effects have not been identified. Collapsin
      Response Mediator Protein 4 (CRMP4) is a cytosolic phosphoprotein known to
      regulate cytoskeletal dynamics and is a known physiological substrate of GSK3. In
      this study, we investigate the role of CRMP4 during mitosis. METHODOLOGY AND
      PRINCIPAL FINDINGS: Here we demonstrate that during mitosis CRMP4 phosphorylation
      is regulated in a GSK3-dependent manner. We show that CRMP4 localizes to spindle
      microtubules during mitosis and loss of CRMP4 disrupts chromosomal alignment and
      mitotic progression. The effect of CRMP4 on chromosomal alignment is dependent on
      phosphorylation by GSK3 identifying CRMP4 as a critical GSK3 substrate during
      mitotic progression. We also provide mechanistic data demonstrating that CRMP4
      regulates spindle microtubules consistent with its known role in the regulation
      of the microtubule cytoskeleton. CONCLUSION AND SIGNIFICANCE: Our findings
      identify CRMP4 as a key physiological substrate of GSK3 in regulating chromosomal
      alignment and mitotic progression through its effect on spindle microtubules.

PMID- 21179546
TI  - Patterns of spatial variation of assemblages associated with intertidal rocky
      shores: a global perspective.
AB  - Assemblages associated with intertidal rocky shores were examined for large scale
      distribution patterns with specific emphasis on identifying latitudinal trends of
      species richness and taxonomic distinctiveness. Seventy-two sites distributed
      around the globe were evaluated following the standardized sampling protocol of
      the Census of Marine Life NaGISA project (www.nagisa.coml.org). There were no
      clear patterns of standardized estimators of species richness along latitudinal
      gradients or among Large Marine Ecosystems (LMEs); however, a strong latitudinal
      gradient in taxonomic composition (i.e., proportion of different taxonomic groups
      in a given sample) was observed. Environmental variables related to natural
      influences were strongly related to the distribution patterns of the assemblages
      on the LME scale, particularly photoperiod, sea surface temperature (SST) and
      rainfall. In contrast, no environmental variables directly associated with human
      influences (with the exception of the inorganic pollution index) were related to
      assemblage patterns among LMEs. Correlations of the natural assemblages with
      either latitudinal gradients or environmental variables were equally strong
      suggesting that neither neutral models nor models based solely on environmental
      variables sufficiently explain spatial variation of these assemblages at a global
      scale. Despite the data shortcomings in this study (e.g., unbalanced sample
      distribution), we show the importance of generating biological global databases
      for the use in large-scale diversity comparisons of rocky intertidal assemblages
      to stimulate continued sampling and analyses.

PMID- 21179547
TI  - HIV tropism and decreased risk of breast cancer.
AB  - BACKGROUND: During the first two decades of the U.S. AIDS epidemic, and unlike
      some malignancies, breast cancer risk was significantly lower for women with
      human immunodeficiency virus (HIV) infection compared to the general population.
      This deficit in HIV-associated breast cancer could not be attributed to
      differences in survival, immune deficiency, childbearing or other breast cancer
      risk factors. HIV infects mononuclear immune cells by binding to the CD4 molecule
      and to CCR5 or CXCR4 chemokine coreceptors. Neoplastic breast cells commonly
      express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has
      been shown to induce apoptosis of neoplastic breast cells. Based on these
      observations, we hypothesized that breast cancer risk would be lower among women
      with CXCR4-tropic HIV infection. METHODS AND FINDINGS: We conducted a breast
      cancer nested case-control study among women who participated in the WIHS and
      HERS HIV cohort studies with longitudinally collected risk factor data and
      plasma. Cases were HIV-infected women (mean age 46 years) who had stored plasma
      collected within 24 months of breast cancer diagnosis and an HIV viral load>=500
      copies/mL. Three HIV-infected control women, without breast cancer, were matched
      to each case based on age and plasma collection date. CXCR4-tropism was
      determined by a phenotypic tropism assay. Odds ratios (OR) and 95% confidence
      intervals (CI) for breast cancer were estimated by exact conditional logistic
      regression. Two (9%) of 23 breast cancer cases had CXCR4-tropic HIV, compared to
      19 (28%) of 69 matched controls. Breast cancer risk was significantly and
      independently reduced with CXCR4 tropism (adjusted odds ratio, 0.10, 95% CI 0.002
      0.84) and with menopause (adjusted odds ratio, 0.08, 95% CI 0.001-0.83).
      Adjustment for CD4+ cell count, HIV viral load, and use of antiretroviral therapy
      did not attenuate the association between infection with CXCR4-tropic HIV and
      breast cancer. CONCLUSIONS: Low breast cancer risk with HIV is specifically
      linked to CXCR4-using variants of HIV. These variants are thought to exclusively
      bind to and signal through a receptor that is commonly expressed on hyperplastic
      and neoplastic breast duct cells. Additional studies are needed to confirm these
      observations and to understand how CXCR4 might reduce breast cancer risk.

PMID- 21179548
TI  - Grifonin-1: a small HIV-1 entry inhibitor derived from the algal lectin,
      Griffithsin.
AB  - BACKGROUND: Griffithsin, a 121-residue protein isolated from a red algal
      Griffithsia sp., binds high mannose N-linked glycans of virus surface
      glycoproteins with extremely high affinity, a property that allows it to prevent
      the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We
      used the sequence of a portion of griffithsin's sequence as a design template to
      create smaller peptides with antiviral and carbohydrate-binding properties.
      METHODOLOGY/RESULTS: The new peptides derived from a trio of homologous beta
      sheet repeats that comprise the motifs responsible for its biological activity.
      Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8+/
      11.0 nM in in vitro TZM-bl assays and an EC(50) of 546.6+/-66.1 nM in p24gag
      antigen release assays. GRFN-1 showed considerable structural plasticity,
      assuming different conformations in solvents that differed in polarity and
      hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on
      intermolecular beta-sheet interactions. Like its parent protein, GRFN-1 bound
      viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface.
      CONCLUSION: Its substantial antiviral activity and low toxicity in vitro suggest
      that GRFN-1 and/or its derivatives may have therapeutic potential as topical
      and/or systemic agents directed against HIV-1.

PMID- 21179550
TI  - Synergistic effect of hyaluronate fragments in retinaldehyde-induced skin
      hyperplasia which is a Cd44-dependent phenomenon.
AB  - BACKGROUND: CD44 is a polymorphic proteoglycan and functions as the principal
      cell-surface receptor for hyaluronate (HA). Heparin-binding epidermal growth
      factor (HB-EGF) activation of keratinocyte erbB receptors has been proposed to
      mediate retinoid-induced epidermal hyperplasia. We have recently shown that
      intermediate size HA fragments (HAFi) reverse skin atrophy by a CD44-dependent
      mechanism. METHODOLOGY AND PRINCIPAL FINDINGS: Treatment of primary mouse
      keratinocyte cultures with retinaldehyde (RAL) resulted in the most significant
      increase in keratinocyte proliferation when compared with other retinoids,
      retinoic acid, retinol or retinoyl palmitate. RAL and HAFi showed a more
      significant increase in keratinocyte proliferation than RAL or HAFi alone. No
      proliferation with RAL was observed in CD44-/- keratinocytes. HA synthesis
      inhibitor, 4-methylumbelliferone inhibited the proliferative effect of RAL. HB
      EGF, erbB1, and tissue inhibitor of MMP-3 blocking antibodies abrogated the RAL-
      or RAL- and HAFi-induced keratinocyte proliferation. Topical application of RAL
      or RAL and HAFi for 3 days caused a significant epidermal hyperplasia in the back
      skin of wild-type mice but not in CD44-/- mice. Topical RAL and HAFi increased
      epidermal CD44 expression, and the epidermal and dermal HA. RAL induced the
      expression of active HB-EGF and erbB1. However, treatment with RAL and HAFi
      showed a more significant increase in pro-HB-EGF when compared to RAL or HAFi
      treatments alone. We then topically applied RAL and HAFi twice a day to the
      forearm skin of elderly dermatoporosis patients. After 1 month of treatment, we
      observed a significant clinical improvement. CONCLUSIONS AND SIGNIFICANCE: Our
      results indicate that (i) RAL-induced in vitro and in vivo keratinocyte
      proliferation is a CD44-dependent phenomenon and requires the presence of HA, HB
      EGF, erbB1 and MMPs, (ii) RAL and HAFi show a synergy in vitro and in vivo in
      mouse skin, and (iii) the combination of RAL and HAFi seems to have an important
      therapeutic effect in dermatoporosis.

PMID- 21179549
TI  - Dynamic emotional and neural responses to music depend on performance expression
      and listener experience.
AB  - Apart from its natural relevance to cognition, music provides a window into the
      intimate relationships between production, perception, experience, and emotion.
      Here, emotional responses and neural activity were observed as they evolved
      together with stimulus parameters over several minutes. Participants listened to
      a skilled music performance that included the natural fluctuations in timing and
      sound intensity that musicians use to evoke emotional responses. A mechanical
      performance of the same piece served as a control. Before and after fMRI
      scanning, participants reported real-time emotional responses on a 2-dimensional
      rating scale (arousal and valence) as they listened to each performance. During
      fMRI scanning, participants listened without reporting emotional responses.
      Limbic and paralimbic brain areas responded to the expressive dynamics of human
      music performance, and both emotion and reward related activations during music
      listening were dependent upon musical training. Moreover, dynamic changes in
      timing predicted ratings of emotional arousal, as well as real-time changes in
      neural activity. BOLD signal changes correlated with expressive timing
      fluctuations in cortical and subcortical motor areas consistent with pulse
      perception, and in a network consistent with the human mirror neuron system.
      These findings show that expressive music performance evokes emotion and reward
      related neural activations, and that music's affective impact on the brains of
      listeners is altered by musical training. Our observations are consistent with
      the idea that music performance evokes an emotional response through a form of
      empathy that is based, at least in part, on the perception of movement and on
      violations of pulse-based temporal expectancies.

PMID- 21179551
TI  - Polyploidization altered gene functions in cotton (Gossypium spp.).
AB  - Cotton (Gossypium spp.) is an important crop plant that is widely grown to
      produce both natural textile fibers and cottonseed oil. Cotton fibers, the
      economically more important product of the cotton plant, are seed trichomes
      derived from individual cells of the epidermal layer of the seed coat. It has
      been known for a long time that large numbers of genes determine the development
      of cotton fiber, and more recently it has been determined that these genes are
      distributed across At and Dt subgenomes of tetraploid AD cottons. In the present
      study, the organization and evolution of the fiber development genes were
      investigated through the construction of an integrated genetic and physical map
      of fiber development genes whose functions have been verified and confirmed. A
      total of 535 cotton fiber development genes, including 103 fiber transcription
      factors, 259 fiber development genes, and 173 SSR-contained fiber ESTs, were
      analyzed at the subgenome level. A total of 499 fiber related contigs were
      selected and assembled. Together these contigs covered about 151 Mb in physical
      length, or about 6.7% of the tetraploid cotton genome. Among the 499 contigs, 397
      were anchored onto individual chromosomes. Results from our studies on the
      distribution patterns of the fiber development genes and transcription factors
      between the At and Dt subgenomes showed that more transcription factors were from
      Dt subgenome than At, whereas more fiber development genes were from At subgenome
      than Dt. Combining our mapping results with previous reports that more fiber QTLs
      were mapped in Dt subgenome than At subgenome, the results suggested a new
      functional hypothesis for tetraploid cotton. After the merging of the two diploid
      Gossypium genomes, the At subgenome has provided most of the genes for fiber
      development, because it continues to function similar to its fiber producing
      diploid A genome ancestor. On the other hand, the Dt subgenome, with its non
      fiber producing D genome ancestor, provides more transcription factors that
      regulate the expression of the fiber genes in the At subgenome. This hypothesis
      would explain previously published mapping results. At the same time, this
      integrated map of fiber development genes would provide a framework to clone
      individual full-length fiber genes, to elucidate the physiological mechanisms of
      the fiber differentiation, elongation, and maturation, and to systematically
      study the functional network of these genes that interact during the process of
      fiber development in the tetraploid cottons.

PMID- 21179552
TI  - Stochastic resonance modulates neural synchronization within and between cortical
      sources.
AB  - Neural synchronization is a mechanism whereby functionally specific brain regions
      establish transient networks for perception, cognition, and action. Direct
      addition of weak noise (fast random fluctuations) to various neural systems
      enhances synchronization through the mechanism of stochastic resonance (SR).
      Moreover, SR also occurs in human perception, cognition, and action. Perception,
      cognition, and action are closely correlated with, and may depend upon,
      synchronized oscillations within specialized brain networks. We tested the
      hypothesis that SR-mediated neural synchronization occurs within and between
      functionally relevant brain areas and thus could be responsible for behavioral
      SR. We measured the 40-Hz transient response of the human auditory cortex to
      brief pure tones. This response arises when the ongoing, random-phase, 40-Hz
      activity of a group of tuned neurons in the auditory cortex becomes synchronized
      in response to the onset of an above-threshold sound at its "preferred"
      frequency. We presented a stream of near-threshold standard sounds in various
      levels of added broadband noise and measured subjects' 40-Hz response to the
      standards in a deviant-detection paradigm using high-density EEG. We used
      independent component analysis and dipole fitting to locate neural sources of the
      40-Hz response in bilateral auditory cortex, left posterior cingulate cortex and
      left superior frontal gyrus. We found that added noise enhanced the 40-Hz
      response in all these areas. Moreover, added noise also increased the
      synchronization between these regions in alpha and gamma frequency bands both
      during and after the 40-Hz response. Our results demonstrate neural SR in several
      functionally specific brain regions, including areas not traditionally thought to
      contribute to the auditory 40-Hz transient response. In addition, we demonstrated
      SR in the synchronization between these brain regions. Thus, both intra- and
      inter-regional synchronization of neural activity are facilitated by the addition
      of moderate amounts of random noise. Because the noise levels in the brain
      fluctuate with arousal system activity, particularly across sleep-wake cycles,
      optimal neural noise levels, and thus SR, could be involved in optimizing the
      formation of task-relevant brain networks at several scales under normal
      conditions.

PMID- 21179553
TI  - Excess mortality rate during adulthood among Danish adoptees.
AB  - BACKGROUND AND OBJECTIVE: Adoption studies have been used to disentangle the
      influence of genes from shared familial environment on various traits and disease
      risks. However, both the factors leading to adoption and living as an adoptee may
      bias the studies with regard to the relative influence of genes and environment
      compared to the general population. The aim was to investigate whether the cohort
      of domestic adoptees used for these studies in Denmark is similar to the general
      population with respect to all-cause mortality and cause-specific mortality
      rates. METHODS: 13,111 adoptees born in Denmark in 1917, or later, and adopted in
      1924 to 1947 were compared to all Danes from the same birth cohorts using
      standardized mortality ratios (SMR). The 12,729 adoptees alive in 1970 were
      similarly compared to all Danes using SMR as well as cause-specific SMR. RESULTS:
      The excess in all-cause mortality before age 65 years in adoptees was estimated
      to be 1.30 (95% CI 1.26-1.35). Significant excess mortality before age 65 years
      was also observed for infections, vascular deaths, cancer, alcohol-related deaths
      and suicide. Analyses including deaths after age 65 generally showed slightly
      less excess in mortality, but the excess was significant for all-cause mortality,
      cancer, alcohol-related deaths and suicides. CONCLUSION: Adoptees have an
      increased all-cause mortality compared to the general population. All major
      specific causes of death contributed, and the highest excess is seen for alcohol
      related deaths.

PMID- 21179554
TI  - Inhibition of stearoyl-CoA desaturase 1 expression induces CHOP-dependent cell
      death in human cancer cells.
AB  - BACKGROUND: Cancer cells present a sustained de novo fatty acid synthesis with an
      increase of saturated and monounsaturated fatty acid (MUFA) production. This
      change in fatty acid metabolism is associated with overexpression of stearoyl-CoA
      desaturase 1 (Scd1), which catalyses the transformation of saturated fatty acids
      into monounsaturated fatty acids (e.g., oleic acid). Several reports demonstrated
      that inhibition of Scd1 led to the blocking of proliferation and induction of
      apoptosis in cancer cells. Nevertheless, mechanisms of cell death activation
      remain to be better understood. PRINCIPAL FINDINGS: In this study, we
      demonstrated that Scd1 extinction by siRNA triggered abolition of de novo MUFA
      synthesis in cancer and non-cancer cells. Scd1 inhibition-activated cell death
      was only observed in cancer cells with induction of caspase 3 activity and PARP
      cleavage. Exogenous supplementation with oleic acid did not reverse the Scd1
      ablation-mediated cell death. In addition, Scd1 depletion induced unfolded
      protein response (UPR) hallmarks such as Xbp1 mRNA splicing, phosphorylation of
      eIF2alpha and increase of CHOP expression. However, the chaperone GRP78
      expression, another UPR hallmark, was not affected by Scd1 knockdown in these
      cancer cells indicating a peculiar UPR activation. Finally, we showed that CHOP
      induction participated to cell death activation by Scd1 extinction. Indeed,
      overexpression of dominant negative CHOP construct and extinction of CHOP
      partially restored viability in Scd1-depleted cancer cells. CONCLUSION: These
      results suggest that inhibition of de novo MUFA synthesis by Scd1 extinction
      could be a promising anti-cancer target by inducing cell death through UPR and
      CHOP activation.

PMID- 21179555
TI  - The role of climate variability in the spread of malaria in Bangladeshi
      highlands.
AB  - BACKGROUND: Malaria is a major public health problem in Bangladesh, frequently
      occurring as epidemics since the 1990s. Many factors affect increases in malaria
      cases, including changes in land use, drug resistance, malaria control programs,
      socioeconomic issues, and climatic factors. No study has examined the
      relationship between malaria epidemics and climatic factors in Bangladesh. Here,
      we investigate the relationship between climatic parameters [rainfall,
      temperature, humidity, sea surface temperature (SST), El Nino-Southern
      Oscillation (ENSO), the normalized difference vegetation index (NDVI)], and
      malaria cases over the last 20 years in the malaria endemic district of
      Chittagong Hill Tracts (CHT). METHODS AND PRINCIPAL FINDINGS: Monthly malaria
      case data from January 1989 to December 2008, monthly rainfall, temperature,
      humidity sea surface temperature in the Bay of Bengal and ENSO index at the Nino
      Region 3 (NINO3) were used. A generalized linear negative binomial regression
      model was developed using the number of monthly malaria cases and each of the
      climatic parameters. After adjusting for potential mutual confounding between
      climatic factors there was no evidence for any association between the number of
      malaria cases and temperature, rainfall and humidity. Only a low NDVI was
      associated with an increase in the number of malaria cases. There was no evidence
      of an association between malaria cases and SST in the Bay of Bengal and NINO3.
      CONCLUSION AND SIGNIFICANCE: It seems counterintuitive that a low NDVI, an
      indicator of low vegetation greenness, is associated with increases in malaria
      cases, since the primary vectors in Bangladesh, such as An. dirus, are associated
      with forests. This relationship can be explained by the drying up of rivers and
      streams creating suitable breeding sites for the vector fauna. Bangladesh has
      very high vector species diversity and vectors suited to these habitats may be
      responsible for the observed results.

PMID- 21179556
TI  - So different, yet so similar: meta-analysis and policy modeling of willingness to
      participate in clinical trials among Brazilians and Indians.
AB  - BACKGROUND: With the global expansion of clinical trials and the expectations of
      the rise of the emerging economies known as BRICs (Brazil, Russia, India and
      China), the understanding of factors that affect the willingness to participate
      in clinical trials of patients from those countries assumes a central role in the
      future of health research. METHODS: We conducted a systematic review and meta
      analysis (SRMA) of willingness to participate in clinical trials among Brazilian
      patients and then we compared it with Indian patients (with results of another
      SRMA previously conducted by our group) through a system dynamics model. RESULTS:
      Five studies were included in the SRMA of Brazilian patients. Our main findings
      are 1) the major motivation for Brazilian patients to participate in clinical
      trials is altruism, 2) monetary reimbursement is the least important factor
      motivating Brazilian patients, 3) the major barrier for Brazilian patients to not
      participate in clinical trials is the fear of side effects, and 4) Brazilian
      patients are more likely willing to participate in clinical trials than Indians.
      CONCLUSION: Our study provides important insights for investigators and sponsors
      for planning trials in Brazil (and India) in the future. Ignoring these results
      may lead to unnecessary fund/time spending. More studies are needed to validate
      our results and for better understanding of this poorly studied theme.

PMID- 21179557
TI  - A rare myelin protein zero (MPZ) variant alters enhancer activity in vitro and in
      vivo.
AB  - BACKGROUND: Myelin protein zero (MPZ) is a critical structural component of
      myelin in the peripheral nervous system. The MPZ gene is regulated, in part, by
      the transcription factors SOX10 and EGR2. Mutations in MPZ, SOX10, and EGR2 have
      been implicated in demyelinating peripheral neuropathies, suggesting that
      components of this transcriptional network are candidates for harboring disease
      causing mutations (or otherwise functional variants) that affect MPZ expression.
      METHODOLOGY: We utilized a combination of multi-species sequence comparisons,
      transcription factor-binding site predictions, targeted human DNA re-sequencing,
      and in vitro and in vivo enhancer assays to study human non-coding MPZ variants.
      PRINCIPAL FINDINGS: Our efforts revealed a variant within the first intron of MPZ
      that resides within a previously described SOX10 binding site is associated with
      decreased enhancer activity, and alters binding of nuclear proteins.
      Additionally, the genomic segment harboring this variant directs tissue-relevant
      reporter gene expression in zebrafish. CONCLUSIONS: This is the first reported
      MPZ variant within a cis-acting transcriptional regulatory element. While we were
      unable to implicate this variant in disease onset, our data suggests that similar
      non-coding sequences should be screened for mutations in patients with
      neurological disease. Furthermore, our multi-faceted approach for examining the
      functional significance of non-coding variants can be readily generalized to
      study other loci important for myelin structure and function.

PMID- 21179558
TI  - Detection of heteroplasmic mitochondrial DNA in single mitochondria.
AB  - BACKGROUND: Mitochondrial DNA (mtDNA) genome mutations can lead to energy and
      respiratory-related disorders like myoclonic epilepsy with ragged red fiber
      disease (MERRF), mitochondrial myopathy, encephalopathy, lactic acidosis and
      stroke (MELAS) syndrome, and Leber's hereditary optic neuropathy (LHON). It is
      not well understood what effect the distribution of mutated mtDNA throughout the
      mitochondrial matrix has on the development of mitochondrial-based disorders.
      Insight into this complex sub-cellular heterogeneity may further our
      understanding of the development of mitochondria-related diseases. METHODOLOGY:
      This work describes a method for isolating individual mitochondria from single
      cells and performing molecular analysis on that single mitochondrion's DNA. An
      optical tweezer extracts a single mitochondrion from a lysed human HL-60 cell.
      Then a micron-sized femtopipette tip captures the mitochondrion for subsequent
      analysis. Multiple rounds of conventional DNA amplification and standard
      sequencing methods enable the detection of a heteroplasmic mixture in the mtDNA
      from a single mitochondrion. SIGNIFICANCE: Molecular analysis of mtDNA from the
      individually extracted mitochondrion demonstrates that a heteroplasmy is present
      in single mitochondria at various ratios consistent with the 50/50 heteroplasmy
      ratio found in single cells that contain multiple mitochondria.

PMID- 21179559
TI  - Rat hypocretin/orexin neurons are maintained in a depolarized state by TRPC
      channels.
AB  - In a previous study we proposed that the depolarized state of the wake-promoting
      hypocretin/orexin (hcrt/orx) neurons was independent of synaptic inputs as it
      persisted in tetrodotoxin and low calcium/high magnesium solutions. Here we show
      first that these cells are hyperpolarized when external sodium is lowered,
      suggesting that non-selective cation channels (NSCCs) could be involved. As
      canonical transient receptor channels (TRPCs) are known to form NSCCs, we looked
      for TRPCs subunits using single-cell RT-PCR and found that TRPC6 mRNA was
      detectable in a small minority, TRPC1, TRPC3 and TRPC7 in a majority and TRPC4
      and 5 in the vast majority (~90%) of hcrt/orx neurons. Using intracellular
      applications of TRPC antibodies against subunits known to form NSCCs, we then
      found that only TRPC5 antibodies elicited an outward current, together with
      hyperpolarization and inhibition of the cells. These effects were blocked by co
      application of a TRPC5 antigen peptide. Voltage-clamp ramps in the presence or
      absence of TRPC5 antibodies indicated the presence of a current with a reversal
      potential close to -15 mV. Application of the non-selective TRPC channel blocker,
      flufenamic acid, had a similar effect, which could be occluded in cells pre
      loaded with TRPC5 antibodies. Finally, using the same TRPC5 antibodies we found
      that most hcrt/orx cells show immunostaining for the TRPC5 subunit. These results
      suggest that hcrt/orx neurons are endowed with a constitutively active non
      selective cation current which depends on TRPC channels containing the TRPC5
      subunit and which is responsible for the depolarized and active state of these
      cells.

PMID- 21179560
TI  - Uptake of aggregating transthyretin by fat body in a Drosophila model for TTR
      associated amyloidosis.
AB  - BACKGROUND: A functional link has been established between the severe
      neurodegenerative disorder Familial amyloidotic polyneuropathy and the enhanced
      propensity of the plasma protein transthyretin (TTR) to form aggregates in
      patients with single point mutations in the TTR gene. Previous work has led to
      the establishment of an experimental model based on transgenic expression of
      normal or mutant forms of human TTR in Drosophila flies. Remarkably, the severity
      of the phenotype was greater in flies that expressed a single copy than with two
      copies of the mutated gene. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we
      analyze the distribution of normal and mutant TTR in transgenic flies, and the
      ultrastructure of TTR-positive tissues to clarify if aggregates and/or amyloid
      filaments are formed. We report the formation of intracellular aggregates of 20
      nm spherules and amyloid filaments in thoracic adipose tissue and in brain glia,
      two tissues that do not express the transgene. The formation of aggregates of
      nanospherules increased with age and was more considerable in flies with two
      copies of mutated TTR. Treatment of human neuronal cells with protein extracts
      prepared from TTR flies of different age showed that the extracts from older
      flies were less toxic than those from younger flies. CONCLUSIONS/SIGNIFICANCE:
      These findings suggest that the uptake of TTR from the circulation and its
      subsequent segregation into cytoplasmic quasi-crystalline arrays of nanospherules
      is part of a mechanism that neutralizes the toxic effect of TTR.

PMID- 21179561
TI  - Similarity and familiarity: Second language sentence recognition in first- and
      second-language multi-talker babble.
AB  - The intelligibility of speech in noisy environments depends not only on the
      functionality of listeners' peripheral auditory systems, but also on cognitive
      factors such as their language learning experience. Previous studies have shown,
      for example, that normal-hearing listeners attending to a non-native language
      have more difficulty identifying speech targets in noisy conditions than do
      native listeners. Furthermore, native listeners have more difficulty
      understanding speech targets in the presence of speech noise in their native
      language versus a foreign language. The present study addresses the role of
      listener language experience with both the target and noise languages by
      examining second-language sentence recognition in first- and second-language
      noise. Native English speakers and non-native English speakers whose native
      language is Mandarin were tested on English sentence recognition in English and
      Mandarin 2-talker babble. Results show that both listener groups experienced
      greater difficulty in English versus Mandarin babble, but that native Mandarin
      listeners experienced a smaller release from masking in Mandarin babble relative
      to English babble. These results indicate that both the similarity between the
      target and noise and the language experience of the listeners contribute to the
      amount of interference listeners experience when listening to speech in the
      presence of speech noise.

PMID- 21179562
TI  - Real-Time Nonlinear Finite Element Computations on GPU - Application to
      Neurosurgical Simulation.
AB  - Application of biomechanical modeling techniques in the area of medical image
      analysis and surgical simulation implies two conflicting requirements: accurate
      results and high solution speeds. Accurate results can be obtained only by using
      appropriate models and solution algorithms. In our previous papers we have
      presented algorithms and solution methods for performing accurate nonlinear
      finite element analysis of brain shift (which includes mixed mesh, different non
      linear material models, finite deformations and brain-skull contacts) in less
      than a minute on a personal computer for models having up to 50.000 degrees of
      freedom. In this paper we present an implementation of our algorithms on a
      Graphics Processing Unit (GPU) using the new NVIDIA Compute Unified Device
      Architecture (CUDA) which leads to more than 20 times increase in the computation
      speed. This makes possible the use of meshes with more elements, which better
      represent the geometry, are easier to generate, and provide more accurate
      results.

PMID- 21179563
TI  - A Perceptual Phonetic Similarity Space for Languages: Evidence from Five Native
      Language Listener Groups.
AB  - The goal of the present study was to devise a means of representing languages in
      a perceptual similarity space based on their overall phonetic similarity. In
      Experiment 1, native English listeners performed a free classification task in
      which they grouped 17 diverse languages based on their perceived phonetic
      similarity. A similarity matrix of the grouping patterns was then submitted to
      clustering and multidimensional scaling analyses. In Experiment 2, an independent
      group of native English listeners sorted the group of 17 languages in terms of
      their distance from English. Experiment 3 repeated Experiment 2 with four groups
      of non-native English listeners: Dutch, Mandarin, Turkish and Korean listeners.
      Taken together, the results of these three experiments represent a step towards
      establishing an approach to assessing the overall phonetic similarity of
      languages. This approach could potentially provide the basis for developing
      predictions regarding foreign-accented speech intelligibility for various
      listener groups, and regarding speech perception accuracy in the context of
      background noise in various languages.

PMID- 21179564
TI  - Affective response to a loved one's pain: insula activity as a function of
      individual differences.
AB  - Individual variability in emotion processing may be associated with genetic
      variation as well as with psychological predispositions such as dispositional
      affect styles. Our previous fMRI study demonstrated that amygdala reactivity was
      independently predicted by affective-cognitive styles (phobic prone or eating
      disorders prone) and genotype of the serotonin transporter in a discrimination
      task of fearful facial expressions. Since the insula is associated with the
      subjective evaluation of bodily states and is involved in human feelings, we
      explored whether its activity could also vary in function of individual
      differences. In the present fMRI study, the association between dispositional
      affects and insula reactivity has been examined in two groups of healthy
      participants categorized according to affective-cognitive styles (phobic prone or
      eating disorders prone). Images of the faces of partners and strangers, in both
      painful and neutral situations, were used as visual stimuli. Interaction analyses
      indicate significantly different activations in the two groups in reaction to a
      loved one's pain: the phobic prone group exhibited greater activation in the left
      posterior insula. These results demonstrate that affective-cognitive style is
      associated with insula activity in pain empathy processing, suggesting a greater
      involvement of the insula in feelings for a certain cohort of people. In the
      mapping of individual differences, these results shed new light on variability in
      neural networks of emotion.

PMID- 21179565
TI  - Microarray-based maps of copy-number variant regions in European and sub-Saharan
      populations.
AB  - The genetic basis of phenotypic variation can be partially explained by the
      presence of copy-number variations (CNVs). Currently available methods for CNV
      assessment include high-density single-nucleotide polymorphism (SNP) microarrays
      that have become an indispensable tool in genome-wide association studies (GWAS).
      However, insufficient concordance rates between different CNV assessment methods
      call for cautious interpretation of results from CNV-based genetic association
      studies. Here we provide a cross-population, microarray-based map of copy-number
      variant regions (CNVRs) to enable reliable interpretation of CNV association
      findings. We used the Affymetrix Genome-Wide Human SNP Array 6.0 to scan the
      genomes of 1167 individuals from two ethnically distinct populations (Europe,
      N=717; Rwanda, N=450). Three different CNV-finding algorithms were tested and
      compared for sensitivity, specificity, and feasibility. Two algorithms were
      subsequently used to construct CNVR maps, which were also validated by processing
      subsamples with additional microarray platforms (Illumina 1M-Duo BeadChip,
      Nimblegen 385K aCGH array) and by comparing our data with publicly available
      information. Both algorithms detected a total of 42669 CNVs, 74% of which
      clustered in 385 CNVRs of a cross-population map. These CNVRs overlap with 862
      annotated genes and account for approximately 3.3% of the haploid human genome.We
      created comprehensive cross-populational CNVR-maps. They represent an extendable
      framework that can leverage the detection of common CNVs and additionally assist
      in interpreting CNV-based association studies.

PMID- 21179566
TI  - Consistent robustness analysis (CRA) identifies biologically relevant properties
      of regulatory network models.
AB  - BACKGROUND: A number of studies have previously demonstrated that "goodness of
      fit" is insufficient in reliably classifying the credibility of a biological
      model. Robustness and/or sensitivity analysis is commonly employed as a secondary
      method for evaluating the suitability of a particular model. The results of such
      analyses invariably depend on the particular parameter set tested, yet many
      parameter values for biological models are uncertain. RESULTS: Here, we propose a
      novel robustness analysis that aims to determine the "common robustness" of the
      model with multiple, biologically plausible parameter sets, rather than the local
      robustness for a particular parameter set. Our method is applied to two published
      models of the Arabidopsis circadian clock (the one-loop [1] and two-loop [2]
      models). The results reinforce current findings suggesting the greater
      reliability of the two-loop model and pinpoint the crucial role of TOC1 in the
      circadian network. CONCLUSIONS: Consistent Robustness Analysis can indicate both
      the relative plausibility of different models and also the critical components
      and processes controlling each model.

PMID- 21179567
TI  - A fluorescence reporter model defines "Tip-DCs" as the cellular source of
      interferon beta in murine listeriosis.
AB  - Production of type I interferons, consisting mainly of multiple IFNalpha subtypes
      and IFNbeta, represents an essential part of the innate immune defense against
      invading pathogens. While in most situations, namely viral infections, this class
      of cytokines is indispensable for host survival they mediate a detrimental effect
      during infection with L. monocytogenes by rendering macrophages insensitive
      towards IFNgamma signalling which leads to a lethal bacterial pathology in mice.
      Due to a lack of suitable analytic tools the precise identity of the cell
      population responsible for type I IFN production remains ill-defined and so far
      these cells have been described to be macrophages. As in general IFNbeta is the
      first type I interferon to be produced, we took advantage of an IFNbeta
      fluorescence reporter-knockin mouse model in which YFP is expressed from a
      bicistronic mRNA linked by an IRES to the endogenous ifnb mRNA to assess the
      IFNbeta production on a single cell level in situ. Our results showed highest
      frequencies and absolute numbers of IFNbeta+ cells in the spleen 24 h after
      infection with L. monocytogenes where they were located predominately in the
      white pulp within the foci of infection. Detailed FACS surface marker analyses,
      intracellular cytokine stainings and T cell proliferation assays revealed that
      the IFNbeta+ cells were a phenotypically and functionally further specialized
      subpopulation of TNF and iNOS producing DCs (Tip-DCs) which are known to be
      essential for the early containment of L. monocytogenes infection. We proved that
      the IFNbeta+ cells exhibited the hallmark characteristics of Tip-DCs as they
      produced iNOS and TNF and possessed T cell priming abilities. These results point
      to a yet unappreciated ambiguous role for a multi-effector, IFNbeta producing
      subpopulation of Tip-DCs in controlling the balance between containment of L.
      monocytogenes infection and effects detrimental to the host driven by IFNbeta.

PMID- 21179568
TI  - A transient transgenic RNAi strategy for rapid characterization of gene function
      during embryonic development.
AB  - RNA interference (RNAi) is a powerful strategy for studying the phenotypic
      consequences of reduced gene expression levels in model systems. To develop a
      method for the rapid characterization of the developmental consequences of gene
      dysregulation, we tested the use of RNAi for "transient transgenic" knockdown of
      mRNA in mouse embryos. These methods included lentiviral infection as well as
      transposition using the Sleeping Beauty (SB) and PiggyBac (PB) transposable
      element systems. This approach can be useful for phenotypic validation of
      putative mutant loci, as we demonstrate by confirming that knockdown of Prdm16
      phenocopies the ENU-induced cleft palate (CP) mutant, csp1. This strategy is
      attractive as an alternative to gene targeting in embryonic stem cells, as it is
      simple and yields phenotypic information in a matter of weeks. Of the three
      methodologies tested, the PB transposon system produced high numbers of
      transgenic embryos with the expected phenotype, demonstrating its utility as a
      screening method.

PMID- 21179569
TI  - FMR1 genotype with autoimmunity-associated polycystic ovary-like phenotype and
      decreased pregnancy chance.
AB  - The FMR1 gene partially appears to control ovarian reserve, with a specific
      ovarian sub-genotype statistically associated with a polycystic ovary (PCO)- like
      phenotype. Some forms of PCO have been associated with autoimmunity. We,
      therefore, investigated in multiple regression analyses associations of ovary
      specific FMR1 genotypes with autoimmunity and pregnancy chances (with in vitro
      fertilization, IVF) in 339 consecutive infertile women (455 IVF cycles), 75 with
      PCO-like phenotype, adjusted for age, race/ethnicity, medication dosage and
      number of oocytes retrieved. Patients included 183 (54.0%) with normal (norm) and
      156 (46%) with heterozygous (het) FMR1 genotypes; 133 (39.2%) demonstrated
      laboratory evidence of autoimmunity: 51.1% of het-norm/low, 38.3% of norm and
      24.2% het-norm/high genotype and sub-genotypes demonstrated autoimmunity
      (p=0.003). Prevalence of autoimmunity increased further in PCO-like phenotype
      patients with het-norm/low genotype (83.3%), remained unchanged with norm (34.0%)
      and decreased in het-norm/high women (10.0%; P<0.0001). Pregnancy rates were
      significantly higher with norm (38.6%) than het-norm/low (22.2%, p=0.001). FMR1
      sub-genotype het-norm/low is strongly associated with autoimmunity and decreased
      pregnancy chances in IVF, reaffirming the importance of the distal long arm of
      the X chromosome (FMR1 maps at Xq27.3) for autoimmunity, ovarian function and,
      likely, pregnancy chance with IVF.

PMID- 21179570
TI  - MicroRNA-related cofilin abnormality in Alzheimer's disease.
AB  - Rod-like structures composed of actin and the actin-binding protein cofilin are
      found in Alzheimer's disease (AD) patients. However, the mechanisms underlying
      formation of these structures and their pathological consequences are still
      largely unknown. We found that microRNAs 103 and 107 repress translation of
      cofilin, and that reduced levels of miR-103 or miR-107 are associated with
      elevated cofilin protein levels and formation of rod-like structures in a
      transgenic mouse model of AD. These results suggest that microRNAs may play an
      important role in cytoskeletal pathology in AD.

PMID- 21179571
TI  - Defining clinical malaria: the specificity and incidence of endpoints from active
      and passive surveillance of children in rural Kenya.
AB  - BACKGROUND: Febrile malaria is the most common clinical manifestation of P.
      falciparum infection, and is often the primary endpoint in clinical trials and
      epidemiological studies. Subjective and objective fevers are both used to define
      the endpoint, but have not been carefully compared, and the relative incidence of
      clinical malaria by active and passive case detection is unknown. METHODS: We
      analyzed data from cohorts under active and passive surveillance, including
      19,462 presentations with fever and 5,551 blood tests for asymptomatic
      parasitaemia. A logistic regression model was used to calculate Malaria
      Attributable Fractions (MAFs) for various case definitions. Incidences of febrile
      malaria by active and passive surveillance were compared in a subset of children
      matched for age and location. RESULTS: Active surveillance identified three times
      the incidence of clinical malaria as passive surveillance in a subset of children
      matched for age and location. Objective fever (temperature>=37.5 degrees C) gave
      consistently higher MAFs than case definitions based on subjective fever.
      CONCLUSION: The endpoints from active and passive surveillance have high
      specificity, but the incidence of endpoints is lower on passive surveillance.
      Subjective fever had low specificity and should not be used in primary endpoint.
      Passive surveillance will reduce the power of clinical trials but may cost
      effectively deliver acceptable sensitivity in studies of large populations.

PMID- 21179572
TI  - Targeting the IL-6 dependent phenotype can identify novel therapies for
      cholangiocarcinoma.
AB  - BACKGROUND: The need for new therapies for cholangiocarcinoma is highlighted by
      their poor prognosis and refractoriness to chemotherapy. Increased production of
      Interleukin-6 promotes cholangiocarcinoma growth and contributes to
      chemoresistance by activating cell survival mechanisms. We sought to identify
      biologically active compounds capable of ameliorating the phenotypic effects of
      IL-6 expression and to explore their potential therapeutic use for
      cholangiocarcinoma. METHODOLOGY: A genomic signature associated with Interleukin
      6 expression in Mz-ChA-1 human malignant cholangiocytes was derived.
      Computational bioinformatics analysis was performed to identify compounds that
      induced inverse gene changes to the signature. The effect of these compounds on
      cholangiocarcinoma growth was then experimentally verified in vitro and in vivo.
      Interactions with other therapeutic agents were evaluated using median effects
      analysis. PRINCIPAL FINDINGS: A group of structurally related compounds,
      nitrendipine, nifedipine and felodipine was identified. All three compounds were
      cytotoxic to Mz-ChA-1 cells with an IC50 for felodipine of 26 uM, nitrendipine,
      44 uM and nifedipine, 15 uM. Similar results were observed in KMCH-1, CC-LP-1 and
      TFK-1 cholangiocarcinoma cell lines. At a fractional effect of 0.5, all three
      agents were synergistic with either camptothecin or gemcitabine in Mz-ChA-1 cells
      in vitro. Co-administration of felodipine and gemcitabine decreased the growth of
      Mz-ChA-1 cell xenografts in nude athymic mice. CONCLUSIONS: Computational
      bioinformatics analysis of phenotype-based genomic expression can be used to
      identify therapeutic agents. Using this drug discovery approach based on
      targeting a defined tumor associated phenotype, we identified compounds with the
      potential for therapeutic use in cholangiocarcinoma.

PMID- 21179573
TI  - Irradiation-induced up-regulation of HLA-E on macrovascular endothelial cells
      confers protection against killing by activated natural killer cells.
AB  - BACKGROUND: Apart from the platelet/endothelial cell adhesion molecule 1 (PECAM
      1, CD31), endoglin (CD105) and a positive factor VIII-related antigen staining,
      human primary and immortalized macro- and microvascular endothelial cells (ECs)
      differ in their cell surface expression of activating and inhibitory ligands for
      natural killer (NK) cells. Here we comparatively study the effects of irradiation
      on the phenotype of ECs and their interaction with resting and activated NK
      cells. METHODOLOGY/PRINCIPAL FINDINGS: Primary macrovascular human umbilical vein
      endothelial cells (HUVECs) only express UL16 binding protein 2 (ULBP2) and the
      major histocompatibility complex (MHC) class I chain-related protein MIC-A (MIC
      A) as activating signals for NK cells, whereas the corresponding immortalized
      EA.hy926 EC cell line additionally present ULBP3, membrane heat shock protein 70
      (Hsp70), intercellular adhesion molecule ICAM-1 (CD54) and HLA-E. Apart from MIC
      B, the immortalized human microvascular endothelial cell line HMEC, resembles the
      phenotype of EA.hy926. Surprisingly, primary HUVECs are more sensitive to Hsp70
      peptide (TKD) plus IL-2 (TKD/IL-2)-activated NK cells than their immortalized EC
      counterpatrs. This finding is most likely due to the absence of the inhibitory
      ligand HLA-E, since the activating ligands are shared among the ECs. The co
      culture of HUVECs with activated NK cells induces ICAM-1 (CD54) and HLA-E
      expression on the former which drops to the initial low levels (below 5%) when NK
      cells are removed. Sublethal irradiation of HUVECs induces similar but less
      pronounced effects on HUVECs. Along with these findings, irradiation also induces
      HLA-E expression on macrovascular ECs and this correlates with an increased
      resistance to killing by activated NK cells. Irradiation had no effect on HLA-E
      expression on microvascular ECs and the sensitivity of these cells to NK cells
      remained unaffected. CONCLUSION/SIGNIFICANCE: These data emphasize that an
      irradiation-induced, transient up-regulation of HLA-E on macrovascular ECs might
      confer protection against NK cell-mediated vascular injury.

PMID- 21179574
TI  - Crystal structure of EHEC intimin: insights into the complementarity between EPEC
      and EHEC.
AB  - Enterohaemorrhagic E. coli (EHEC) O157:H7 is a primary food-borne bacterial
      pathogen capable of causing life-threatening human infections which poses a
      serious challenge to public health worldwide. Intimin, the bacterial outer
      membrane protein, plays a key role in the initiating process of EHEC infection.
      This activity is dependent upon translocation of the intimin receptor (Tir), the
      intimin binding partner of the bacteria-encoded host cell surface protein.
      Intimin has attracted considerable attention due to its potential function as an
      antibacterial drug target. Here, we report the crystal structure of the Tir
      binding domain of intimin (Int188) from E. coli O157:H7 at 2.8 A resolution,
      together with a mutant (IntN916Y) at 2.6 A. We also built the structural model of
      EHEC intimin-Tir complex and analyzed the key binding residues. It suggested that
      the binding pattern of intimin and Tir between EHEC and Enteropathogenic E. coli
      (EPEC) adopt a similar mode and they can complement with each other. Detailed
      structural comparison indicates that there are four major points of structural
      variations between EHEC and EPEC intimins: one in Domain I (Ig-like domain), the
      other three located in Domain II (C-type lectin-like domain). These variations
      result in different binding affinities. These findings provide structural insight
      into the binding pattern of intimin to Tir and the molecular mechanism of EHEC
      O157: H7.

PMID- 21179575
TI  - A universal approach to eliminate antigenic properties of alpha-gliadin peptides
      in celiac disease.
AB  - Celiac disease is caused by an uncontrolled immune response to gluten, a
      heterogeneous mixture of wheat storage proteins, including the alpha-gliadins. It
      has been shown that alpha-gliadins harbor several major epitopes involved in the
      disease pathogenesis. A major step towards elimination of gluten toxicity for
      celiac disease patients would thus be the elimination of such epitopes from alpha
      gliadins. We have analyzed over 3,000 expressed alpha-gliadin sequences from 11
      bread wheat cultivars to determine whether they encode for peptides potentially
      involved in celiac disease. All identified epitope variants were synthesized as
      peptides and tested for binding to the disease-associated HLA-DQ2 and HLA-DQ8
      molecules and for recognition by patient-derived alpha-gliadin specific T cell
      clones. Several specific naturally occurring amino acid substitutions were
      identified for each of the alpha-gliadin derived peptides involved in celiac
      disease that eliminate the antigenic properties of the epitope variants. Finally,
      we provide proof of principle at the peptide level that through the systematic
      introduction of such naturally occurring variations alpha-gliadins genes can be
      generated that no longer encode antigenic peptides. This forms a crucial step in
      the development of strategies to modify gluten genes in wheat so that it becomes
      safe for celiac disease patients. It also provides the information to design and
      introduce safe gluten genes in other cereals, which would exhibit improved
      quality while remaining safe for consumption by celiac disease patients.

PMID- 21179576
TI  - Selective induction of DNA repair pathways in human B cells activated by CD4+ T
      cells.
AB  - Greater than 75% of all hematologic malignancies derive from germinal center (GC)
      or post-GC B cells, suggesting that the GC reaction predisposes B cells to
      tumorigenesis. Because GC B cells acquire expression of the highly mutagenic
      enzyme activation-induced cytidine deaminase (AID), GC B cells may require
      additional DNA repair capacity. The goal of this study was to investigate whether
      normal human B cells acquire enhanced expression of DNA repair factors upon AID
      induction. We first demonstrated that several DNA mismatch repair, homologous
      recombination, base excision repair, and ATR signaling genes were overexpressed
      in GC B cells relative to naive and memory B cells, reflecting activation of a
      process we have termed somatic hyperrepair (SHR). Using an in vitro system, we
      next characterized activation signals required to induce AID expression and SHR.
      Although AID expression was induced by a variety of polyclonal activators, SHR
      induction strictly required signals provided by contact with activated CD4+ T
      cells, and B cells activated in this manner displayed reduced levels of DNA
      damage-induced apoptosis. We further show the induction of SHR is independent of
      AID expression, as GC B cells from AID-/-mice retained heightened expression of
      SHR proteins. In consideration of the critical role that CD4+ T cells play in
      inducing the SHR process, our data suggest a novel role for CD4+ T cells in the
      tumor suppression of GC/post-GC B cells.

PMID- 21179577
TI  - Amyloid-beta triggers the release of neuronal hexokinase 1 from mitochondria.
AB  - Brain accumulation of the amyloid-beta peptide (Abeta) and oxidative stress
      underlie neuronal dysfunction and memory loss in Alzheimer's disease (AD).
      Hexokinase (HK), a key glycolytic enzyme, plays important pro-survival roles,
      reducing mitochondrial reactive oxygen species (ROS) generation and preventing
      apoptosis in neurons and other cell types. Brain isozyme HKI is mainly associated
      with mitochondria and HK release from mitochondria causes a significant decrease
      in enzyme activity and triggers oxidative damage. We here investigated the
      relationship between Abeta-induced oxidative stress and HK activity. We found
      that Abeta triggered HKI detachment from mitochondria decreasing HKI activity in
      cortical neurons. Abeta oligomers further impair energy metabolism by decreasing
      neuronal ATP levels. Abeta-induced HKI cellular redistribution was accompanied by
      excessive ROS generation and neuronal death. 2-deoxyglucose blocked Abeta-induced
      oxidative stress and neuronal death. Results suggest that Abeta-induced cellular
      redistribution and inactivation of neuronal HKI play important roles in oxidative
      stress and neurodegeneration in AD.

PMID- 21179578
TI  - Assortative mixing in close-packed spatial networks.
AB  - BACKGROUND: In recent years, there is aroused interest in expressing complex
      systems as networks of interacting nodes. Using descriptors from graph theory, it
      has been possible to classify many diverse systems derived from social and
      physical sciences alike. In particular, folded proteins as examples of self
      assembled complex molecules have also been investigated intensely using these
      tools. However, we need to develop additional measures to classify different
      systems, in order to dissect the underlying hierarchy. METHODOLOGY AND PRINCIPAL
      FINDINGS: In this study, a general analytical relation for the dependence of
      nearest neighbor degree correlations on degree is derived. Dependence of local
      clustering on degree is shown to be the sole determining factor of assortative
      versus disassortative mixing in networks. The characteristics of networks
      constructed from spatial atomic/molecular systems exemplified by self-organized
      residue networks built from folded protein structures and block copolymers,
      atomic clusters and well-compressed polymeric melts are studied. Distributions of
      statistical properties of the networks are presented. For these densely-packed
      systems, assortative mixing in the network construction is found to apply, and
      conditions are derived for a simple linear dependence. CONCLUSIONS: Our analyses
      (i) reveal patterns that are common to close-packed clusters of atoms/molecules,
      (ii) identify the type of surface effects prominent in different close-packed
      systems, and (iii) associate fingerprints that may be used to classify networks
      with varying types of correlations.

PMID- 21179579
TI  - Distinct functions for the Drosophila piRNA pathway in genome maintenance and
      telomere protection.
AB  - Transposons and other selfish DNA elements can be found in all phyla, and
      mobilization of these elements can compromise genome integrity. The piRNA (PIWI
      interacting RNA) pathway silences transposons in the germline, but it is unclear
      if this pathway has additional functions during development. Here we show that
      mutations in the Drosophila piRNA pathway genes, armi, aub, ago3, and rhi, lead
      to extensive fragmentation of the zygotic genome during the cleavage stage of
      embryonic divisions. Additionally, aub and armi show defects in telomere
      resolution during meiosis and the cleavage divisions; and mutations in lig-IV,
      which disrupt non-homologous end joining, suppress these fusions. By contrast,
      lig-IV mutations enhance chromosome fragmentation. Chromatin immunoprecipitation
      studies show that aub and armi mutations disrupt telomere binding of HOAP, which
      is a component of the telomere protection complex, and reduce expression of a
      subpopulation of 19- to 22-nt telomere-specific piRNAs. Mutations in rhi and
      ago3, by contrast, do not block HOAP binding or production of these piRNAs. These
      findings uncover genetically separable functions for the Drosophila piRNA
      pathway. The aub, armi, rhi, and ago3 genes silence transposons and maintain
      chromosome integrity during cleavage-stage embryonic divisions. However, the aub
      and armi genes have an additional function in assembly of the telomere protection
      complex.

PMID- 21179580
TI  - Striatal spine plasticity in Parkinson's disease.
AB  - Striatal dopamine (DA) denervation results in a significant loss of dendritic
      spines on medium spiny projection neurons in Parkinson's disease. In 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine-treated parkinsonian monkeys, spines contacted
      either by cortical or thalamic glutamatergic terminals are severely affected on
      both direct and indirect striatofugal neurons. In rodents, indirect pathway
      neurons appear to be more sensitive, at least in early stages of acute dopamine
      denervation. The remaining corticostriatal and thalamostriatal axo-spinous
      synapses undergo complex ultrastructural remodeling consistent with increased
      synaptic activity in the DA-denervated primate striatum, which may explain the
      pathophysiological overactivity of the corticostriatal system reported in various
      animal models of parkinsonism. The calcium-mediated regulation of the
      transcription factor myocyte enhancer factor 2 was recognized as a possible
      underlying mechanism for striatal spine plasticity. Future studies to determine
      how alterations in striatal spine plasticity contribute to the symptomatology of
      parkinsonism are warranted.

PMID- 21179581
TI  - Memory formation in reversal learning of the honeybee.
AB  - In reversal learning animals are first trained with a differential learning
      protocol, where they learn to respond to a reinforced odor (CS+) and not to
      respond to a non-reinforced odor (CS-). Once they respond correctly to this rule,
      the contingencies of the conditioned stimuli are reversed, and animals learn to
      adjust their response to the new rule. This study investigated the effect of a
      protein synthesis inhibitor (emetine) on the memory formed after reversal
      learning in the honeybee Apis mellifera. Two groups of bees were studied: summer
      bees and winter bees, each yielded different results. Blocking protein synthesis
      in summer bees inhibits consolidation of the excitatory learning following
      reversal learning whereas it blocked the consolidation of the inhibitory learning
      in winter bees. These findings suggest that excitatory and inhibitory learning
      may involve different molecular processes in bees, which are seasonally
      dependent.

PMID- 21179582
TI  - Vocalization Induced CFos Expression in Marmoset Cortex.
AB  - All non-human primates communicate with conspecifics using vocalizations, a
      system involving both the production and perception of species-specific vocal
      signals. Much of the work on the neural basis of primate vocal communication in
      cortex has focused on the sensory processing of vocalizations, while relatively
      little data are available for vocal production. Earlier physiological studies in
      squirrel monkeys had shed doubts on the involvement of primate cortex in vocal
      behaviors. The aim of the present study was to identify areas of common marmoset
      (Callithrix jacchus) cortex that are potentially involved in vocal communication.
      In this study, we quantified cFos expression in three areas of marmoset cortex -
      frontal, temporal (auditory), and medial temporal - under various vocal
      conditions. Specifically, we examined cFos expression in these cortical areas
      during the sensory, motor (vocal production), and sensory-motor components of
      vocal communication. Our results showed an increase in cFos expression in
      ventrolateral prefrontal cortex as well as the medial and lateral belt areas of
      auditory cortex in the vocal perception condition. In contrast, subjects in the
      vocal production condition resulted in increased cFos expression only in dorsal
      premotor cortex. During the sensory-motor condition (antiphonal calling),
      subjects exhibited cFos expression in each of the above areas, as well as
      increased expression in perirhinal cortex. Overall, these results suggest that
      various cortical areas outside primary auditory cortex are involved in primate
      vocal communication. These findings pave the way for further physiological
      studies of the neural basis of primate vocal communication.

PMID- 21179583
TI  - To head or to heed? Beyond the surface of selective action inhibition: a review.
AB  - To head rather than heed to temptations is easier said than done. Since tempting
      actions are often contextually inappropriate, selective suppression is invoked to
      inhibit such actions. Thus far, laboratory tasks have not been very successful in
      highlighting these processes. We suggest that this is for three reasons. First,
      it is important to dissociate between an early susceptibility to making stimulus
      driven impulsive but erroneous actions, and the subsequent selective suppression
      of these impulses that facilitates the selection of the correct action. Second,
      studies have focused on mean or median reaction times (RT), which conceals the
      temporal dynamics of action control. Third, studies have focused on group means,
      while considering individual differences as a source of error variance. Here, we
      present an overview of recent behavioral and imaging studies that overcame these
      limitations by analyzing RT distributions. As will become clear, this approach
      has revealed variations in inhibitory control over impulsive actions as a
      function of task instructions, conflict probability, and between-trial
      adjustments (following conflict or following an error trial) that are hidden if
      mean RTs are analyzed. Next, we discuss a selection of behavioral as well as
      imaging studies to illustrate that individual differences are meaningful and help
      understand selective suppression during action selection within samples of young
      and healthy individuals, but also within clinical samples of patients diagnosed
      with attention deficit/hyperactivity disorder or Parkinson's disease.

PMID- 21179584
TI  - A reinforcement learning model of precommitment in decision making.
AB  - Addiction and many other disorders are linked to impulsivity, where a suboptimal
      choice is preferred when it is immediately available. One solution to impulsivity
      is precommitment: constraining one's future to avoid being offered a suboptimal
      choice. A form of impulsivity can be measured experimentally by offering a choice
      between a smaller reward delivered sooner and a larger reward delivered later.
      Impulsive subjects are more likely to select the smaller-sooner choice; however,
      when offered an option to precommit, even impulsive subjects can precommit to the
      larger-later choice. To precommit or not is a decision between two conditions:
      (A) the original choice (smaller-sooner vs. larger-later), and (B) a new
      condition with only larger-later available. It has been observed that
      precommitment appears as a consequence of the preference reversal inherent in non
      exponential delay-discounting. Here we show that most models of hyperbolic
      discounting cannot precommit, but a distributed model of hyperbolic discounting
      does precommit. Using this model, we find (1) faster discounters may be more or
      less likely than slow discounters to precommit, depending on the precommitment
      delay, (2) for a constant smaller-sooner vs. larger-later preference, a higher
      ratio of larger reward to smaller reward increases the probability of
      precommitment, and (3) precommitment is highly sensitive to the shape of the
      discount curve. These predictions imply that manipulations that alter the
      discount curve, such as diet or context, may qualitatively affect precommitment.

PMID- 21179585
TI  - Time to go our separate ways: opposite effects of study duration on priming and
      recognition reveal distinct neural substrates.
AB  - Amnesic patients have difficulties recognizing when stimuli are repeated, even
      though their responses to stimuli can change as a function of repetition in
      indirect tests of memory - a pattern known as priming without recognition.
      Likewise, experimental manipulations can impair recognition in healthy
      individuals while leaving priming relatively unaffected, and priming and
      recognition have been associated with distinct neural correlates in these
      circumstances. Does this evidence necessarily indicate that priming and
      recognition rely on distinct brain systems? An alternative explanation is that
      recognition is merely more sensitive to amnestic insults and experimental
      manipulations than is priming, and that both priming and recognition are produced
      by a single brain system. If so, then experimental manipulations would tend to
      drive priming and recognition in the same direction, albeit to a greater extent
      for one versus the other in some circumstances. We found evidence to the contrary
      - that manipulating study duration has opposite effects on priming versus
      recognition. Studying objects for one-quarter second led to worse recognition
      than studying objects for 2 s, whereas the opposite was true for priming (greater
      for one-quarter-second study than two-second study). Furthermore, distinct
      electrophysiological repetition effects were associated with priming versus
      recognition. We therefore conclude that study duration had opposite effects on
      priming and recognition, and on the engagement of implicit versus explicit memory
      systems. These findings call into question single-process accounts of priming and
      recognition, and substantiate previous behavioral, neuropsychological, and
      neuroimaging dissociations between implicit and explicit memory.

PMID- 21179586
TI  - Reactivation, retrieval, replay and reconsolidation in and out of sleep:
      connecting the dots.
AB  - The neurobiology of memory has taken on a new look over the past decade. Re
      discovery of cue-dependent amnesia, wide availability of functional imaging tools
      and increased dialog among clinicians, cognitive psychologists, behavioral
      neuroscientists, and neurobiologists have provided impetus for the search for new
      paradigms for the study of memory. Memory is increasingly viewed as an open-ended
      process, with retrieval being recognized as an intricate part of the encoding
      process. New memories are always made on the background of past experience, so
      that every consolidation is, in fact reconsolidation, serving to update and
      strengthen memories after retrieval. Spontaneous reactivation of memory circuits
      occurs during sleep and there is converging evidence from rodent and human
      studies that this is an important part of the extended off-line memory
      processing. The noradrenergic neuromodulatory system is engaged at retrieval,
      facilitating recall. The noradrenergic system is also activated during sleep
      after learning and noradrenergic neurons fire in concert with cortical
      oscillations that are associated with reactivation of memory circuits. We suggest
      that the noradrenergic system and perhaps other neuromodulatory systems, may be a
      key to linking off-line memory reactivation, retrieval, and memory
      reconsolidation processes at both synaptic and systems levels, in and out of
      sleep.

PMID- 21179587
TI  - Applications of patient-specific induced pluripotent stem cells; focused on
      disease modeling, drug screening and therapeutic potentials for liver disease.
AB  - The recent advances in the induced pluripotent stem cell (iPSC) research have
      significantly changed our perspectives on regenerative medicine by providing
      researchers with a unique tool to derive disease-specific stem cells for study.
      In this review, we describe the human iPSC generation from developmentally
      diverse origins (i.e. endoderm-, mesoderm-, and ectoderm- tissue derived human
      iPSCs) and multistage hepatic differentiation protocols, and discuss both basic
      and clinical applications of these cells including disease modeling, drug
      toxicity screening/drug discovery, gene therapy and cell replacement therapy.

PMID- 21179589
TI  - Analysis of microsatellite DNA markers reveals no genetic differentiation between
      wild and hatchery populations of Pacific threadfin in Hawaii.
AB  - Pacific threadfin, Polydactylus sexfilis, is popular fish in recreational
      fishing, as well as aquaculture in Hawaii. Its natural population has been
      continuously declining in the past several decades. Microsatellite DNA markers
      are useful DNA-based tool for monitoring Pacific threadfin populations. In this
      study, fifteen Microsatellite (MS) DNA markers were identified from a partial
      genomic Pacific threadfin DNA library enriched in CA repeats, and six highly
      polymorphic microsatellite loci were employed to analyze genetic similarity and
      differences between the wild population and hatchery population in Oahu Island. A
      total of 37 alleles were detected at the six MS loci in the two populations.
      Statistical analysis of fixation index (F(ST)) and analysis of molecular variance
      (AMOVA) showed no genetic differentiation between the wild and hatchery
      populations (F(ST) = 0.001, CI(95%) = -0.01-0.021). Both high genetic diversity
      (H(o) = 0.664-0.674 and H(e) = 0.710-0.715) and Hardy-Weinberg equilibrium were
      observed in the wild and hatchery populations. Results of genetic bottleneck
      analysis indicated that the hatchery was founded with sufficient numbers of
      brooders as inbreeding coefficient is very low (F(IS) = 0.052-0.072) in both wild
      and hatchery populations. Further studies are needed for comprehensive
      determinations of genetic varieties of primary founder broodstocks and successive
      offspring of the hatchery and wild populations with increased number of Pacific
      threadfin sample collections.

PMID- 21179588
TI  - SRp20 is a proto-oncogene critical for cell proliferation and tumor induction and
      maintenance.
AB  - Tumor cells display a different profile of gene expression than their normal
      counterparts. Perturbations in the levels of cellular splicing factors can alter
      gene expression, potentially leading to tumorigenesis. We found that splicing
      factor SRp20 (SFRS3) is highly expressed in cancers. SRp20 regulated the
      expression of Forkhead box transcription factor M1 (FoxM1) and two of its
      transcriptional targets, PLK1 and Cdc25B, and controlled cell cycle progression
      and proliferation. Cancer cells with RNAi-mediated reduction of SRp20 expression
      exhibited G2/M arrest, growth retardation, and apoptosis. Increased SRp20
      expression in rodent fibroblasts promoted immortal cell growth and
      transformation. More importantly, we found that SRp20 promoted tumor induction
      and the maintenance of tumor growth in nude mice and rendered immortal rodent
      fibroblasts tumorigenic. Collectively, these results suggest that increased SRp20
      expression in tumor cells is a critical step for tumor initiation, progression,
      and maintenance.

PMID- 21179590
TI  - Microbial and bioconversion production of D-xylitol and its detection and
      application.
AB  - D-Xylitol is found in low content as a natural constituent of many fruits and
      vegetables. It is a five-carbon sugar polyol and has been used as a food additive
      and sweetening agent to replace sucrose, especially for non-insulin dependent
      diabetics. It has multiple beneficial health effects, such as the prevention of
      dental caries, and acute otitis media. In industry, it has been produced by
      chemical reduction of D-xylose mainly from photosynthetic biomass hydrolysates.
      As an alternative method of chemical reduction, biosynthesis of D-xylitol has
      been focused on the metabolically engineered Saccharomyces cerevisiae and Candida
      strains. In order to detect D-xylitol in the production processes, several
      detection methods have been established, such as gas chromatography (GC)-based
      methods, high performance liquid chromatography (HPLC)-based methods, LC-MS
      methods, and capillary electrophoresis methods (CE). The advantages and
      disadvantages of these methods are compared in this review.

PMID- 21179591
TI  - Guardian ad litem, a potentially expensive invitation to either the mismanagement
      or management of patients with cognitive disorders.
AB  - The children of a multiple sclerosis (MS) patient filed a guardian ad litem case
      to be brought against the patient. The basis for the petition was that the MS
      patient had a significant reduction is his mental competence. The children were
      not aware that hyperthermia could adversely affect the brain of MS patients. The
      patient's urologist recommended he have a suprapubic cystostomy done in a
      hospital. Passage of the two channel Foley catheter into his bladder immediately
      resolved his urinary tract infection, fever, and difficulty in communicating.
      Despite this dramatic improvement in his health from the urologic treatment, he
      was now faced with resolving his children's petition for a guardian ad litem that
      would allow them to control his estate including his residence and financial
      retirement assets. A judge supported this petition by requesting that the patient
      with MS pay for his children's attorney fees, 24 hour nursing home services that
      duplicated his own hired personal care assistants, the salary of the guardian ad
      litem, the attorney fees for the guardian ad litem, and payment for a
      psychological evaluation. The state law should be changed to require that the
      petitioner have adequate income to pay for his/her attorney as well as the salary
      of the guardian ad litem to prevent mismanagement of patients with cognitive
      disorders. In addition, the guardian ad litem should be an attorney or a
      registered nurse. The care of disabled individuals subjected to litigation should
      be coordinated by an attorney or registered nurse.

PMID- 21179592
TI  - Variable Selection for Qualitative Interactions.
AB  - In this article we discuss variable selection for decision making with focus on
      decisions regarding when to provide treatment and which treatment to provide.
      Current variable selection techniques were developed for use in a supervised
      learning setting where the goal is prediction of the response. These techniques
      often downplay the importance of interaction variables that have small predictive
      ability but that are critical when the ultimate goal is decision making rather
      than prediction. We propose two new techniques designed specifically to find
      variables that aid in decision making. Simulation results are given along with an
      application of the methods on data from a randomized controlled trial for the
      treatment of depression.

PMID- 21179593
TI  - Angular Synchronization by Eigenvectors and Semidefinite Programming.
AB  - The angular synchronization problem is to obtain an accurate estimation (up to a
      constant additive phase) for a set of unknown angles theta(1), ..., theta(n) from
      m noisy measurements of their offsets theta(i) - theta(j) mod 2pi. Of particular
      interest is angle recovery in the presence of many outlier measurements that are
      uniformly distributed in [0, 2pi) and carry no information on the true offsets.
      We introduce an efficient recovery algorithm for the unknown angles from the top
      eigenvector of a specially designed Hermitian matrix. The eigenvector method is
      extremely stable and succeeds even when the number of outliers is exceedingly
      large. For example, we successfully estimate n = 400 angles from a full set of
      m=(4002) offset measurements of which 90% are outliers in less than a second on a
      commercial laptop. The performance of the method is analyzed using random matrix
      theory and information theory. We discuss the relation of the synchronization
      problem to the combinatorial optimization problem Max-2-Lin mod L and present a
      semidefinite relaxation for angle recovery, drawing similarities with the Goemans
      Williamson algorithm for finding the maximum cut in a weighted graph. We present
      extensions of the eigenvector method to other synchronization problems that
      involve different group structures and their applications, such as the time
      synchronization problem in distributed networks and the surface reconstruction
      problems in computer vision and optics.

PMID- 21179594
TI  - The role of pramipexole in a severe Parkinson's disease model in mice.
AB  - BACKGROUND: Pramipexole is one of a new generation of dopamine agonists. Recently
      there have been questions regarding its neuroprotective effects. These effects
      have been tested against various insults, which have yielded conflicting results.
      METHODS: In this study, we introduced a combination of 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)/paraquat to induce a severe Parkinson's disease model.
      The mice, after receiving the combination of toxins, were evaluated using
      mortality rates and immunohistochemistry for degenerating tyrosine hydroxylase
      positive neurons. RESULTS AND CONCLUSIONS: Pramipexole was tested for its
      capacity to offer protection against neurotoxic the effects of MPTP/paraquat in
      this model; however, the results showed no improvement with pramipexole therapy.

PMID- 21179595
TI  - Quetiapine in the treatment of psychosis in Parkinson's disease.
AB  - Psychosis (delusions and/or hallucinations) is a common nonmotor feature of
      Parkinson's disease (PD). Use of the older 'typical' antipsychotic drugs led to
      worsening of motor symptoms. The introduction of 'atypical' antipsychotics opened
      up a range of therapeutic options. These agents include clozapine, risperidone,
      olanzapine, aripiprazole and quetiapine. All have been used to treat psychosis in
      PD with varying success. Clozapine is the only drug with proven efficacy. We
      review the evidence for the efficacy of quetiapine. Eight open-label studies have
      assessed quetiapine use in 191 patients, with improvement in psychosis recorded
      in 152 (80%). In addition to the open-label studies, there have been two single
      blind, randomized trials comparing quetiapine and clozapine. These studies
      suggest that quetiapine has similar efficacy to clozapine in controlling
      psychosis. Following the promising results of the open-label and clozapine
      comparison studies, five randomized, controlled trials (RCTs) have been performed
      to further establish the efficacy of quetiapine. Unfortunately, the results have
      been disappointing. The only positive placebo-controlled study excluded patients
      with delusions, which seem to be harder to treat than hallucinations. The four
      negative RCTs discussed seriously undermine the evidence from the open-label
      studies. The differences in design and interpretation of the RCTs emphasizes the
      need for further large, well-controlled trials, using strict inclusion criteria,
      appropriate psychosis rating scales, carer input and clinical significance.
      Currently, many physicians continue to cautiously offer a trial of low-dose
      quetiapine empirically. Clozapine should be considered in patients who can
      tolerate the required blood monitoring.

PMID- 21179596
TI  - Evolving expectations around early management of multiple sclerosis.
AB  - Multiple sclerosis is a progressive inflammatory disease of the central nervous
      system. With prevention or at least delay of disease progression as a key target
      in the management of multiple sclerosis, current opinion on treatment encourages
      early intervention with well-tolerated disease-modifying treatments in order to
      optimize long-term clinical outcomes. Patients presenting with a clinically
      isolated syndrome (CIS) may progress to clinically definite multiple sclerosis,
      and clinical trials have demonstrated that early treatment with interferon beta
      can reduce the conversion rate. Cognitive impairment may already be present in
      patients with CISs. Today there is evolving evidence that cognitive impairment
      may be relevant for prognosis and that early treatment with interferon beta may
      also have a protective effect on the cognitive function. As an accumulation of
      neuronal loss is now considered to underlie the development of persistent
      disability in multiple sclerosis, it is crucial that treatment can protect
      against neuronal damage. In addition to its anti-inflammatory activity,
      interferon beta may have direct and indirect neuroprotective effects, and several
      studies have explored the role of interferon beta in regulating neuroprotective
      factors. With over 15 years of clinical experience as evidence, the long-term
      safety and efficacy of interferon beta treatment is unquestionable. Results from
      the CIS studies have demonstrated the high percentage of patients converting to
      clinically definite multiple sclerosis without treatment and the short- and long
      term benefits of an early use of disease-modifying treatments. These findings
      support starting disease-modifying treatment as soon as the diagnosis of MS is
      reasonably formulated.

PMID- 21179598
TI  - Aminoglycoside-induced mutation suppression (stop codon readthrough) as a
      therapeutic strategy for Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is the most common, lethal, X-linked genetic
      disease, affecting 1 in 3500 newborn males. It is caused by mutations in the DMD
      gene. Owing to the large size of the gene, the mutation rate in both germline and
      somatic cells is very high. Nearly 13-15% of DMD cases are caused by nonsense
      mutations leading to premature termination codons in the reading frame that
      results in truncated dystrophin protein. Currently there is no cure for DMD. The
      only available treatment is the use of glucocorticoids that have modest
      beneficial effects accompanied by significant side effects. Different therapeutic
      strategies have been developed ranging from gene therapy to exon skipping and
      nonsense mutation suppression to produce the full-length protein. These
      strategies have shown promise in the mdx mouse model of muscular dystrophy where
      they have been reported to ameliorate the dystrophic phenotype and correct the
      physiological defects in the membrane. Each of these molecular approaches are
      being investigated in clinical trials. Here we review nonsense mutation
      suppression by aminoglycosides as a therapeutic strategy to treat DMD with
      special emphasis on gentamicin-induced readthrough of disease-causing premature
      termination codons.

PMID- 21179597
TI  - Possible sites of action of the new calcitonin gene-related peptide receptor
      antagonists.
AB  - Migraine is considered a neurovascular disease affecting more than 10% of the
      general population. Currently available drugs for the acute treatment of migraine
      are vasoconstrictors, which have limitations in their therapeutic use. The
      calcitonin gene-related peptide (CGRP) has a key role in migraine, where levels
      of CGRP are increased during acute migraine attacks. CGRP is expressed throughout
      the central and peripheral nervous system, consistent with control of
      vasodilatation and transmission of nociceptive information. In migraine, CGRP is
      released from the trigeminal system. At peripheral synapses CGRP results in
      vasodilatation via receptors on the smooth muscle cells. At central synapses,
      CGRP acts postjunctionally on second-order neurons to transmit pain centrally via
      the brainstem and midbrain to higher cortical pain regions. The recently
      developed CGRP-receptor antagonists have demonstrated clinical efficacy in the
      treatment of acute migraine attacks. A remaining question is their site of
      action. The CGRP-receptor components (calcitonin receptor-like receptor, receptor
      activity modifying protein 1 and receptor component protein) are found to
      colocalize in the smooth muscle cells of intracranial arteries and in large-sized
      neurons in the trigeminal ganglion. The CGRP receptor has also been localized
      within parts of the brain and the brainstem. The aim of this paper is to review
      recent localization studies of CGRP and its receptor components within the
      nervous system and to discuss whether these sites could be possible targets for
      the CGRP-receptor antagonists.

PMID- 21179600
TI  - New treatment option for partial-onset seizures: efficacy and safety of
      lacosamide.
AB  - More than 30% of epilepsy patients remain refractory despite the advent of new
      antiepileptic drugs (AEDs) over two decades. Although a small percentage of these
      refractory patients may become seizure free when a new AED is added, combined
      administration of AEDs or the application of novel AEDs is the most common
      therapeutic option when surgical treatment cannot be offered. The most recently
      approved AED in Europe and the USA is lacosamide (LCM), which offers new
      mechanisms of action and favorable safety profiles. This article reviews LCM's
      molecular mechanisms of action, pharmacokinetic profiles as well as efficacy and
      safety from phase II and III clinical trials. In addition, comparison between LCM
      and other existing AEDs is discussed.

PMID- 21179601
TI  - Treating epilepsy across its different stages.
AB  - Epilepsy is a chronic condition requiring long-term treatment with drugs that
      have intrinsic limitations. Antiepileptic drugs (AEDs) are effective in
      suppressing seizures but do not alter the disease process. They have a suboptimal
      tolerability profile and can be teratogenic. Second-generation compounds may be
      better tolerated but no more effective than traditional AEDs. In this light, as
      drug therapy is purely symptomatic, acute symptomatic seizures (i.e. seizures
      occurring in close temporal relationship with acute CNS insults) may require
      treatment only until recovery or stabilization of the injury. Treatment of the
      first unprovoked seizure may be considered in patients with abnormal EEG and
      imaging findings and in those in whom the relapse has severe social, emotional
      and personal implications. In these cases and in patients with epilepsy (i.e.
      repeated unprovoked seizures), drugs for partial seizures supported by class I
      regulatory trials or pragmatic trials are oxcarbazepine in children,
      carbamazepine or lamotrigine in adults, and lamotrigine or gabapentin in the
      elderly. Pragmatic trials support use of valproate for generalized seizures,
      except for women of childbearing age for whom the drug should be tailored to the
      individual patient. The lowest maintenance dose should be chosen, based on the
      efficacy and tolerability of the assigned drug. If the first monotherapy fails,
      the safety profile of a drug is important when opting for another monotherapy or
      for an add-on therapy. The epilepsy syndrome and the social, psychological and
      emotional profile of the patient all contribute to the individualization of
      treatment discontinuation after long-term seizure remission.

PMID- 21179602
TI  - Practical considerations on the use of rituximab in autoimmune neurological
      disorders.
AB  - Rituximab (Mabthera, Rituxan) is a chimeric human/murine monoclonal antibody
      against CD-20 surface antigen expressed on B-cells. Rituximab, by causing B-cell
      depletion, appears to be effective in several autoimmune disorders; it has been
      approved for rheumatoid arthritis and is a promising new agent in the treatment
      of several autoimmune neurological disorders. A controlled study in patients with
      relapsing remitting multiple sclerosis has shown that rituximab significantly
      reduces the number of new MRI lesions and improves clinical outcome; it also
      showed some promise in a subset of patients with primary progressive MS. The drug
      is also effective in a number of patients with Devic's disease, myasthenia
      gravis, autoimmune neuropathies, and inflammatory myopathies. The apparent
      effectiveness of rituximab has moved B-cells into the center stage of clinical
      and laboratory investigation of autoimmune neurological disorders. We review the
      evidence-based effectiveness of rituximab in neurological disorders based on
      controlled trials and anecdotal reports, including our own experience, and
      address the immunobiology of B-cells in autoimmune central nervous system (CNS)
      and peripheral nervous system (PNS) disorders. In addition, we provide practical
      guidelines on how best to use this drug in clinical practice and highlight its
      potential toxicity.

PMID- 21179603
TI  - Treatment options in trigeminal neuralgia.
AB  - The incidence of trigeminal neuralgia (TN) is 4.3 per 100,000 persons per year,
      with a slightly higher incidence for women (5.9/100,000) compared with men
      (3.4/100,000). There is a lack of certainty regarding the aetiology and
      pathophysiology of TN. The treatment of TN can be very challenging despite the
      numerous options patients and physicians can choose from. This multitude of
      treatment options poses the question as to which treatment fits which patient
      best. The preferred medical treatment for TN consists of anticonvulsant drugs,
      muscle relaxants and neuroleptic agents. Large-scale placebo-controlled clinical
      trials are scarce. For patients refractory to medical therapy, Gasserian ganglion
      percutaneous techniques, gamma knife surgery and microvascular decompression are
      the most promising invasive treatment options.

PMID- 21179604
TI  - Pharmacotherapy in Parkinson's disease: case studies.
AB  - Parkinson's disease is a common neurodegenerative disorder with the particular
      feature of having various available treatments with proven efficacy. However, no
      treatment is curative. Recent trial results provided data for the discussion
      about the potential disease-modifying effect of new drugs as well as of other
      therapeutic strategies. The changing clinical phenotype following the progression
      of the disease multiplies the number of treatment targets and makes the
      application of recommendations from guidelines or other treatment algorithms to
      the individual patient a complex task. In the present manuscript, we discuss the
      treatment management of three case studies illustrating different stages of
      disease with distinct phenomenology. The proposed therapeutic alternatives are
      discussed based on the best data available; that is, treatment guidelines,
      clinical trial results or observational data.

PMID- 21179605
TI  - A preclinical trial of sialic acid metabolites on distal myopathy with rimmed
      vacuoles/hereditary inclusion body myopathy, a sugar-deficient myopathy: a
      review.
AB  - Distal myopathy with rimmed vacuoles (DMRV), also called hereditary inclusion
      body myopathy (hIBM), is a moderately progressive hereditary muscle disorder
      affecting young adults. DMRV/hIBM is characterized clinically by muscle atrophy
      and weakness initially involving the distal muscles, and pathologically by the
      presence of small angular fibers, formation of rimmed vacuoles and deposition of
      various proteins in the muscle fibers. This disease is known to be caused by
      mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
      gene, which encodes the essential enzyme in sialic acid biosynthesis, leading to
      a reduction of sialic acid levels in the serum and skeletal muscles of affected
      patients. As it is a metabolic disease, metabolite supplementation is
      theoretically one of the therapeutic options. In this review, recent animal
      models for DMRV/hIBM are briefly characterized followed by a focus on the
      administration of sialic acid metabolites as a reliable therapeutic option to
      DMRV/hIBM with the following points highlighted: the property of compounds, the
      pharmacokinetic metabolism in vivo, and the therapeutic effects on the DMRV/hIBM
      mouse model.

PMID- 21179606
TI  - Antiviral agents in Alzheimer's disease: hope for the future?

PMID- 21179607
TI  - Optical coherence tomography as a potential readout in clinical trials.
AB  - Optical coherence tomography (OCT) is a noninvasive tool used for measuring
      tissue at micrometer resolution. It has been extensively applied to ocular
      pathologies and is now being studied as a biomarker in various neurologic
      conditions. The retina represents a unique environment for study, with
      unmyelinated axons that directly synapse into the central nervous system. When
      trying to quantify axonal degradation in neurologic disease, the currently used
      imaging modalities are limited in sensitivity and specificity. Early data suggest
      that several neurologic conditions have pathologic changes in the retinal nerve
      fiber layer of the eye, creating a potential surrogate marker for
      neurodegeneration. OCT has the potential to become a noninvasive, reproducible
      test for axonal degeneration that could become an invaluable tool for measuring
      the efficacy of potential neuroprotective agents. If the natural history of
      neurodegeneration, as measured by OCT, can be documented in diseases such as
      Alzheimer's, Parkinson's and multiple sclerosis, then OCT can be used to measure
      alterations in the rate of degeneration when treatment is applied. Thus, OCT
      represents a new, promising technology for documenting outcomes in
      neuroprotection trials.

PMID- 21179608
TI  - Reversible cerebral vasoconstriction syndrome: an under-recognized clinical
      emergency.
AB  - Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by
      recurrent thunderclap headaches and reversible cerebral vasoconstrictions. RCVS
      is more common than previously thought and should be differentiated from
      aneurismal subarachnoid hemorrhage. RCVS can be spontaneous or evoked by
      pregnancy or exposure to vasoactive substances. Patients tend to be middle-aged
      women but pediatric patients have been seen. Up to 80% of sufferers have
      identifiable triggers. Thunderclap headaches tend to recur daily and last for a
      period of around 2 weeks, while the vasoconstrictions may last for months. About
      one-third of patients have blood pressure surges accompanying headache attacks.
      The potential complications of RCVS include posterior reversible encephalopathy
      syndrome, ischemic strokes over watershed zones, cortical subarachnoid hemorrhage
      and intracerebral hemorrhage. Magnetic resonance images including angiography and
      venography and lumbar punctures are the studies of choice, whereas catheter
      angiography should not be implemented routinely. Patients with a mean flow
      velocity of the middle cerebral artery greater than 120 cm/s shown by
      transcranial color-coded sonography have a greater risk of ischemic complications
      than those without. The pathophysiology of RCVS remains unknown; sympathetic
      hyperactivity may play a role. Open-label trials showed calcium channel blockers,
      such as nimodipine may be an effective treatment in prevention of thunderclap
      headache attacks. In severe cases, intra-arterial therapy may be considered. Most
      patients with RCVS recover without sequelae; however, relapse has been reported
      in a small proportion of patients.

PMID- 21179609
TI  - Therapeutic developments in spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA), a potentially devastating disease marked by
      progressive weakness and muscle atrophy resulting from the dysfunction and loss
      of motor neurons of the spinal cord, has emerged in recent years as an attractive
      target for therapeutic intervention. Caused by a homozygous mutation to the
      Survival of Motor Neurons 1 (SMN1) gene on chromosome 5q, the severity of the
      clinical phenotype in SMA is modulated by the function of a related protein,
      Survival of Motor Neurons 2 (SMN2). SMN2 predominantly produces an unstable SMN
      transcript lacking exon 7; only about 10% of the transcription product produces a
      full-length, functional SMN protein. Several therapeutic strategies have targeted
      this gene with the goal of producing increased full-length SMN transcript,
      thereby modifying the underlying mechanism. Drugs that have increased SMN2
      function, in vitro, are now explored for potential therapeutic benefit in this
      disease. Alternative approaches, including neuroprotective, muscle anabolic, gene
      and cell replacement strategies, also hold promise. The recent advances in
      preclinical research and the development of a wider range of animal models for
      SMA continue to provide cautious optimism that effective treatments for SMA will
      eventually emerge.

PMID- 21179610
TI  - Hypothalamic deep brain stimulation in the treatment of chronic cluster headache.
AB  - Cluster headache (CH) is a short-lasting unilateral headache associated with
      ipsilateral craniofacial autonomic manifestations. A positron emission tomography
      (PET) study has shown that the posterior hypothalamus is activated during CH
      attacks, suggesting that hypothalamic hyperactivity plays a key role in CH
      pathophysiology. On this basis, stimulation of the ipsilateral posterior
      hypothalamus was hypothesized to counteract such hyperactivity to prevent
      intractable CH. Ten years after its introduction, hypothalamic stimulation has
      been proved to successfully prevent attacks in more than 60% of 58 hypothalamic
      implanted drug-resistant chronic CH patients. The implantation procedure has
      generally been proved to be safe, although it carries a small risk of brain
      haemorrhage. Long-term stimulation is safe, and nonsymptomatic impairment of
      orthostatic adaptation is the only noteworthy change. Microrecording studies will
      make it possible to better identify the target site. Neuroimaging investigations
      have shown that hypothalamic stimulation activates ipsilateral trigeminal
      complex, but with no immediate perceived sensation within the trigeminal
      distribution. Other studies on the pain threshold in chronically stimulated
      patients showed increased threshold for cold pain in the distribution of the
      first trigeminal branch ipsilateral to stimulation. These studies suggest that
      activation of the hypothalamus and of the trigeminal system are both necessary,
      but not sufficient to generate CH attacks. In addition to the hypothalamus, other
      unknown brain areas are likely to play a role in the pathophysiology of this
      illness. Hypothalamus implantation is associated with a small risk of
      intracerebral haemorrhage and must be performed by an expert neurosurgical team,
      in selected patients.

PMID- 21179612
TI  - Atacicept: targeting B cells in multiple sclerosis.
AB  - Multiple sclerosis (MS) has traditionally been considered to be a T-cell-mediated
      disease. However, there is an increasing body of evidence for the involvement of
      B cells and autoantibodies in the pathology of this disease, providing a
      rationale for treatments directed against B cells. In this paper we summarize
      evidence for the key role of B cells in the immunopathology of MS and review data
      supporting the use of a novel B-cell targeted therapy, atacicept, in this
      condition. Atacicept is a human recombinant fusion protein that comprises the
      binding portion of a receptor for both BLyS (B-Lymphocyte Stimulator) and APRIL
      (A PRoliferation-Inducing Ligand), two cytokines that have been identified as
      important regulators of B-cell maturation, function and survival. Atacicept has
      shown selective effects on cells of the B-cell lineage, acting on mature B cells
      and blocking plasma cells and late stages of B-cell development while sparing B
      cell progenitors and memory cells. The efficacy of atacicept in animal models of
      autoimmune disease and the biological activity of atacicept in patients with
      systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) has been
      demonstrated. Clinical studies were initiated to investigate the safety,
      tolerability and efficacy of atacicept in patients with MS. An unexpected
      increase in inflammatory activity in one of the trials, however, led to
      suspension of all atacicept trials in MS.

PMID- 21179613
TI  - Therapeutic strategies in childhood multiple sclerosis.
AB  - Multiple sclerosis (MS) in children and adolescents accounts for 3-10% of the
      whole MS population, and is characterized by a relapsing course in almost all
      cases. The frequency of relapses is higher than in adult onset MS, at least in
      the first years of evolution. The objective of treatment is to speed the recovery
      after a relapse, to prevent the occurrence of relapses, and to prevent disease
      progression and neurodegeneration. The use of drugs for MS in children and
      adolescents has not been studied in clinical trials, so their use is mainly based
      on results from trials in adults and from observational studies. There is a
      consensus to treat acute relapses with intravenous high-dose corticosteroids. The
      possibility of preventing relapses and disease progression is based on the use of
      immunomodulatory agents. Interferon-beta (IFNB) and glatiramer acetate (GA) have
      been demonstrated to be safe and well tolerated in pediatric MS patients, and
      also to reduce relapse rate and disease progression. Cyclophosphamide and
      natalizumab could be offered as second-line treatment in patients with a poor
      response to IFNB or GA. New oral and injectable drugs will be available in the
      near future: if safe and well tolerated in the long-term follow up of adults with
      MS, they could be tested in the pediatric MS population.

PMID- 21179614
TI  - Possible clinical outcome measures for clinical trials in patients with multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease
      with both clinical and pathological heterogeneity. The complexity of the MS
      population has offered challenges to the measurement of MS disease progression in
      therapeutic trials. The current standard clinical outcome measures are relapse
      rate, Expanded Disability Severity Scale (EDSS), and the MS Functional Composite
      (MSFC). These measures each have strengths and some weakness. Two additional
      measures, the six-minute walk and accelerometry, show promise in augmenting
      current measures. MS therapeutics is a quickly advancing field which requires
      sensitive clinical outcome measures that can detect small changes in disability
      that reliably reflect long-term changes in sustained disease progression in a
      complex population. A single clinical outcome measure of sustained disease
      progression may remain elusive. Rather, an integration of current and new outcome
      measures may be most appropriate and utilization of different measures depending
      on the MS population and stage of the disease may be preferred.

PMID- 21179615
TI  - The use of rotigotine in the treatment of restless legs syndrome.
AB  - Restless legs syndrome (RLS) is a neurological disorder characterized by an urge
      to move the legs often accompanied by unpleasant sensations. Symptoms appear
      during periods of rest or inactivity, particularly in the evening and at night,
      and are usually relieved by movement. The prevalence of RLS among Whites is
      approximately 5-15%. RLS can be distinguished into primary and secondary forms.
      Most patients (70-80%) are affected by the primary form of RLS. The uncomfortable
      sensations related to RLS often cause a minimal discomfort, thus a therapeutic
      approach is not necessary. However, almost 3% of the general population reports
      to be affected by severe symptoms of RLS, requiring pharmacological treatment.
      Secondary forms of RLS are relieved by the remission of the underlying clinical
      condition. Dopamine agonists are considered to be first-line treatments for
      primary RLS. Rotigotine is a nonergoline dopamine agonist with selectivity for
      D1, D2 and D3 receptors. It is administered once a day in the form of an adhesive
      matrix patch. The efficacy and safety of the drug in patients with primary RLS
      has been demonstrated by four clinical trials using dosages of 0.5, 1, 2, 3 and 4
      mg/24 h. A dose-response relationship was observed between the dosages of 0.5 and
      3 mg/24 h. Side effects were usually mild, the most frequent being skin reaction
      at the site of patch application. More trials are ongoing and results will soon
      be published for the long-term (5 years) treatment of RLS with rotigotine
      transdermal patches. Rotigotine is a promising drug for the treatment of RLS. Its
      continuous delivery throughout 24 h makes it especially indicated for those cases
      also presenting daytime symptoms, and for those presenting the so-called
      augmentation syndrome after prolonged treatment with L-dopa or dopamine agonists.

PMID- 21179617
TI  - The use of gabapentin enacarbil in the treatment of restless legs syndrome.
AB  - Restless legs syndrome (RLS) is a common sleep-related neurological disorder that
      is characterized by the urge to move, worsening at rest, improvement with
      activity, and worsening in the evening and night. Dopamine agonists are usually
      the first-line therapy. Other agents including benzodiazepines, narcotics, and
      anticonvulsants have been used to treat RLS. Gabapentin has been shown to improve
      RLS in a small number of clinical studies, but is limited by its short half-life
      and variable bioavailability. Gabapentin enacarbil is a novel prodrug of
      gabapentin designed to overcome these pharmacokinetic limitations. In vitro and
      in vivo studies have demonstrated that gabapentin enacarbil has improved
      absorption, bioavailability and pharmacokinetics compared with gabapentin. Phase
      II and III studies have demonstrated that gabapentin enacarbil is generally well
      tolerated and is useful in the treatment of RLS.

PMID- 21179616
TI  - Multiple system atrophy: current and future approaches to management.
AB  - Multiple system atrophy (MSA) is a rare neurodegenerative disorder without any
      effective treatment in slowing or stopping disease progression. It is
      characterized by poor levodopa responsive Parkinsonism, cerebellar ataxia,
      pyramidal signs and autonomic failure in any combination. Current therapeutic
      strategies are primarily based on dopamine replacement and improvement of
      autonomic failure. However, symptomatic management remains disappointing and no
      curative treatment is yet available. Recent experimental evidence has confirmed
      the key role of alpha-synuclein aggregation in the pathogenesis of MSA. Referring
      to this hypothesis, transgenic and toxic animal models have been developed to
      assess candidate drugs for MSA. The standardization of diagnosis criteria and
      assessment procedures will allow large multicentre clinical trials to be
      conducted. In this article we review the available symptomatic treatment, recent
      results of studies investigating potential neuroprotective drugs, and future
      approaches for the management in MSA.

PMID- 21179618
TI  - Chemotherapeutics in the treatment of multiple sclerosis.
AB  - The likely pathogenic mechanisms of multiple sclerosis (MS) provide a sound
      rationale for investigating the efficacy of drugs possessing immunosuppressive or
      immunomodulatory properties. With proven efficacy, safety and tolerability,
      interferon beta formulations and glatiramer acetate have become the mainstay of
      initial treatment for patients with relapsing forms of MS. More recently,
      natalizumab, a humanized monoclonal antibody (mAb) against the cellular adhesion
      molecule alpha4-integrin, has been employed for patients with an inadequate
      response or lack of tolerability to an alternate MS therapy, or as initial
      therapy for patients with severe disease. Various agents initially developed for
      oncological indications, either as chemotherapeutics or mAbs, may also have
      current or future uses in MS treatment. Mitoxantrone is currently the only
      chemotherapeutic agent approved for treatment of MS in the United States, while
      in parts of Europe azathioprine is approved and widely used for MS treatment.
      Other chemotherapeutics that have been tested in MS to date include
      cyclophosphamide, methotrexate, cladribine, and the mAbs alemtuzumab and
      rituximab. While there has been varying evidence of efficacy for these compounds,
      each appears to be associated with serious risks that require careful
      consideration and management. Given the risks that have been demonstrated for
      available chemotherapeutic agents and while long-term postmarketing safety data
      are still not available for those agents in development, it seems prudent to
      carefully assess the possible use of chemotherapeutics in the treatment of MS. A
      thorough risk-benefit analysis is becoming increasingly important in the
      assessment of therapeutic options for this disabling disease.

PMID- 21179619
TI  - Natalizumab in pediatric multiple sclerosis patients.
AB  - Pediatric multiple sclerosis (MS) comprises 2-5% of all cases of MS. Although
      first-line disease-modifying therapy (DMT) including interferons and glatiramer
      acetate appear to be well tolerated in this population, recent work has suggested
      that a growing number of children suffer from disease which is resistant to
      treatment with these therapies. Natalizumab is a therapy which, although
      associated with a 1 : 1000 risk for progressive multifocal leukoencephalopathy
      (PML), has been shown to be well tolerated in the adult population and may lead
      to disease remission in adults with highly active disease. Reports of use of this
      therapy in the pediatric population with highly active disease have been
      published. This paper reviews current experience with the use of natalizumab in
      the pediatric MS population, with attention to potential risks and possible long
      term outcomes in this population.

PMID- 21179620
TI  - An update on the treatment of Sydenham's chorea: the evidence for established and
      evolving interventions.
AB  - Over 320 years after Thomas Sydenham described the condition labelled Sydenham's
      chorea, it remains poorly understood. The disorder is an antineuronal antibody
      mediated neuropsychiatric disorder caused by a poststreptococcal, autoimmune
      condition affecting control of movement, mood, behaviour and potentially the
      heart. The treatment remains empirical, and is less than optimal. There are few
      large clinically controlled trials. Recommendations for optimal management remain
      inconsistent and are hampered by the side effects from pharmacotherapy. Care for
      patients should be targeted at primary treatment (penicillin and bed rest),
      secondary palliation (symptomatic medication) and supportive (social) care. Small
      studies have demonstrated trends to support the use of immunoglobulins and
      steroids as therapeutic interventions for children affected by Sydenham's chorea.

PMID- 21179622
TI  - Acute stroke and cytomegalovirus encephalitis: a coincidence?

PMID- 21179623
TI  - Consistency of the Borderline Diagnosis at Admission vs. Discharge: Among
      Psychiatric Inpatients.

PMID- 21179621
TI  - Anti-aquaporin-4 antibodies in Devic's neuromyelitis optica: therapeutic
      implications.
AB  - Devic's neuromyelitis optica (DNMO) is a demyelinating and inflammatory disease
      of the central nervous system (CNS) essentially restricted to the spinal cord and
      the optic nerves. It is a rare disorder with a prevalence estimated at less than
      1/100,000 in Western countries. Since the first description by Eugene Devic in
      1894, the relationship between DNMO and multiple sclerosis (MS) has been
      controversial. Recent clinical, epidemiological, pathological and immunological
      data demonstrate that MS and DNMO are distinct entities. This distinction between
      DNMO and MS is crucial, as prognosis and treatment are indeed different. DNMO is
      now considered to be an autoimmune, antibody-mediated disease especially since
      the identification of a specific serum autoantibody, named NMO-IgG and directed
      against the main water channel of the CNS, aquaporin-4 (AQP4). The assessment of
      AQP4 antibodies (Abs) has initially been proposed to differentiate DNMO and MS.
      It has also enlarged the clinical spectrum of DNMO and proved to be helpful in
      predicting relapses and conversion to DNMO after a first episode of
      longitudinally extensive transverse myelitis or isolated optic neuritis. Lastly,
      the discovery of the pathogenic role of AQP4 Abs in DNMO leads to a better
      understanding of detailed DNMO immunopathology and the elaboration of relevant
      novel treatment strategies specific to DNMO. In this review, we summarize the
      present and future therapeutic implications generated by the discovery of the
      various pathogenic mechanisms of AQP4 Abs in DNMO pathophysiology.

PMID- 21179624
TI  - On split treatment.

PMID- 21179625
TI  - On Psychiatrists being Doctors.

PMID- 21179626
TI  - The biopsychosocial consequences of pathological gambling.

PMID- 21179627
TI  - Validity of the parent young mania rating scale in a community mental health
      setting.
AB  - The objective of this study was to examine the potential of using the Parent
      Young Mania Rating Scale (P-YMRS) to distinguish pediatric bipolar disorder from
      other psychiatric conditions. The design of the study was a retrospective chart
      review. The setting of the study was community mental health. Participants
      included 130 children and adolescents. Measurements were based on P-YMRS scores.
      An ANOVA revealed a significant difference between mean scores of patients with
      and without bipolar disorder. A receiver operating characteristic (ROC) analysis
      revealed that the P-YMRS is very good at predicting group membership and
      suggested a cutoff of 18 or higher for the presence of bipolar disorder. The
      authors conclude that the P-YMRS should be useful to differentiate pediatric
      bipolar disorder from other mental health conditions.

PMID- 21179628
TI  - Antipsychotic-induced movement disorders: evaluation and treatment.

PMID- 21179629
TI  - Normalization of risperidone-induced hyperprolactinemia with the addition of
      aripiprazole.
AB  - The objective of this study was to monitor metabolic changes, including
      hyperprolactinemia, in adolescents medicated with atypical antipsychotics,
      especially when polypharmacy is involved. This study specifically followed
      risperidone-induced hyperprolactinemia in adolescents (14 male patients and 2
      female patients) after aripiprazole was added to begin transitioning to another
      atypical antipsychotic. No other changes were made in the medication regimen.
      Risperidone was continued at the previous dose during the transition. This sample
      consists of 16 adolescents, 13 to 18 years old, treated in long-term residential
      care for behavior problems. Diagnoses included bipolar disorder, schizoaffective
      disorder, psychotic depression, and post-traumatic stress disorder. In
      retrospective chart review, all 16 of the adolescents (100%) experienced complete
      normalization of prolactin levels. Thirteen of the adolescents had normal
      prolactin levels within two weeks and the other three normalized within three
      months of the addition of aripiprazole while still on risperidone and other
      previous medications at the original doses. The authors concluded the addition of
      aripiprazole rapidly normalizes risperidone-induced hyperprolactinemia.

PMID- 21179630
TI  - Aripiprazole augmentation of clozapine: in refractory schizophrenia.

PMID- 21179631
TI  - Pharmacotherapy for alcohol dependence.
AB  - Alcoholism is a major public health problem that is detrimental to the affected
      individuals as well as to society as a whole. It has been popular belief that
      alcohol dependence can be controlled through will power, skill building, and
      support. Therefore, psychosocial therapies have historically been the most
      utilized treatments for alcohol use disorders.(1).

PMID- 21179632
TI  - Community service models for schizophrenia: evidence-based implications and
      future directions.
AB  - Schizophrenia is a chronic relapsing and remitting mental illness with lifetime
      prevalence between 0.40 to 1.4 percent. Most people with schizophrenia are
      treated in psychiatric units of local general hospitals for short periods of time
      when acutely ill. With the worldwide trend toward closure of asylums and
      institutions in the 1950s, there has been an increasing focus on treatment in the
      community. Community mental health teams (CMHT) are the kernel of community
      treatment. Although their composition and modus operandi differ according to
      patient need, all models claim superiority over outcomes of long inpatient stay.
      Case management, assertive outreach, and crisis resolution sometimes compete for
      resources. What is the evidence for their efficacy? What is the right mix of
      their use? As we discuss these, we propose that there may be room for the
      application of established industry models of service delivery, such as Just-in
      Time (JIT), in the treatment of patients with schizophrenia.

PMID- 21179633
TI  - Dietary intake of patients with schizophrenia.

PMID- 21179634
TI  - Long-acting risperidone in the treatment of schizophrenia: an evidence-based
      approach.

PMID- 21179636
TI  - Psychiatrists are Doctors, too: A Call for Mutual Respect and Communication Among
      all Treating Physicians.

PMID- 21179635
TI  - A primer on psychotherapy treatment of anorexia nervosa in adolescents.

PMID- 21179637
TI  - Aripiprazole augmentation of combination escitalopram and sertraline in the
      treatment of refractory obsessive-compulsive disorder.

PMID- 21179638
TI  - Lofexidine for opioid detoxification.

PMID- 21179639
TI  - Seasonal affective disorder: an overview and update.
AB  - Seasonal affective disorder (SAD), characterized by fall/winter major depression
      with spring/summer remission, is a prevalent mental health problem. SAD etiology
      is not certain, but available models focus on neurotransmitters, hormones,
      circadian rhythm dysregulation, genetic polymorphisms, and psychological factors.
      Light therapy is established as the best available treatment for SAD. Alternative
      and/or supplementary approaches involving medications, cognitive-behavioral
      therapy, and exercise are currently being developed and evaluated. Given the
      complexity of the disorder, interdisciplinary research stands to make a
      significant contribution to advancing our understanding of SAD conceptualization
      and treatment.

PMID- 21179640
TI  - Attention deficit/hyperactivity disorder: pharmacotherapy.
AB  - Pharmacotherapy, one of the effective modalities of treatment for attention
      deficit/hyperactivity disorder (ADHD), was discovered serendipitously and, until
      recently, consisted primarily of short-acting methylphenidate and
      dextroamphetamine compounds. The US Food and Drug Administration's (FDA) approval
      of Concerta in 2000 followed by approval of additional long-acting
      methylphenidate (Ritalin LA; Metadate CD) and amphetamine formulations (Adderall
      XR) expanded the repertoire. By providing sustained efficacy for most of the
      school day, mid-day administration is avoided, privacy is preserved, and
      adherence to treatment improves. In 2001, an isomer preparation of
      methylphenidate, Focalin, was approved, and in 2002, Strattera, a selective
      noradrenergic agent expanded treatment options to non-controlled agents. At this
      time, stimulant preparations continue to remain the first-line agents due to
      their unparalleled efficacy and safety record. However, current treatment remains
      empirical due to lack of scientific data guiding the choice of agent as well as
      dose.

PMID- 21179641
TI  - Psychotropic-induced weight gain and potential pharmacologic treatment
      strategies.

PMID- 21179642
TI  - Split treatment: a measurement of coordination between psychiatrists.
AB  - The objective of this study was to examine the adherence rates of psychiatrists
      with APA standards for coordination of care in split treatment. Coordination of
      care in split treatment is monitored from claims paid data in an academic MBHO as
      an ongoing quality improvement activity. For an 18-month period, 93 psychiatrists
      were identified with 559 patients in split treatment and were mailed a survey.
      Surveys were controlled for change of providers. Self-report survey results were
      obtained from 69 psychiatrists for 295 patients in split treatment. The average
      rate of coordination was 66 percent; however, the distribution was bimodal with
      36 percent of psychiatrists always coordinating and 26 percent never
      coordinating. Not obtaining a release accounted for 87 percent of non
      coordination. In conclusion, while coordination of care in split treatment is an
      APA standard of practice, only 36 percent of psychiatrists fully complied. That
      one third of patients in split treatment did not receive coordinated care
      suggests a need for improvement to meet the APA standards of practice and avoid
      legal exposure.

PMID- 21179643
TI  - Evaluating the use of the wilbarger intervention with schizophrenic patients: a
      pilot study.
AB  - Individuals with schizophrenia have difficulty processing sensory information.
      The authors hypothesized that the Wilbarger intervention, an occupational therapy
      technique successfully used to treat children with sensory integration deficits,
      might prove beneficial if used with schizophrenic patients. Thirty inpatients
      diagnosed with schizophrenia or schizoaffective disorders voluntarily
      participated. Each was evaluated using the sensory integration subscale of the
      Neurological Evaluation Scale (NES) both pre- and post-intervention. The
      Wilbarger was scheduled to be administered five times per day for seven days per
      week for four weeks. Participants averaged 19.5 days (mean) in the study
      (median=27.5 days) and received 80.4 (mean) (106.5 median) interventions.Those
      receiving 90 or more interventions improved significantly on the graphesthesia
      subtest (t(28)=2.498; p<0.019), the right/left confusion subtest (t(28)=2.373;
      p<0.025) and the post-total score (t(28)=2.184; p<0.037). Sensory subscales of
      the NES statistically improved after use of the Wilbarger intervention. Further
      studies are planned to determine the duration and clinical significance of the
      noted changes.

PMID- 21179644
TI  - Non-psychotic hallucinations.

PMID- 21179645
TI  - Psychiatrists are Doctors Too (Revisited).

PMID- 21179646
TI  - Kudos to psychiatry 2005.

PMID- 21179647
TI  - Antipsychotic-induced movement disorders.

PMID- 21179648
TI  - Post-traumatic stress disorder and acute stress disorder I: their nature and
      assessment considerations.
AB  - POST-TRAUMATIC STRESS DISORDER (PTSD) is a common and often chronic and disabling
      anxiety disorder that can develop after exposure to highly stressful events
      characterized by actual or threatened harm to the self or others. This is the
      first of two articles summarizing the nature and treatment of PTSD and the
      associated condition of acute stress disorder (ASD). The present article presents
      the diagnostic criteria for PTSD and ASD, summarizes the epidemiology of exposure
      to trauma and resulting PTSD/ASD, discusses implications of these data for
      assessment and treatment, and provides a summary of several useful assessment
      instruments. A companion paper to be published in a future issue of Psychiatry
      2005 will provide a summary of empirically supported treatments, both
      psychological and pharmacological, for PTSD and ASD.

PMID- 21179650
TI  - The vulnerable faces of pathological gambling.
AB  - Pathological gambling is an emerging psychiatric disorder that has medical,
      psychiatric, and social consequences. Recently, research has been focusing on
      identifying which portions of the population are most vulnerable to developing
      problems related to ongoing gambling. Specific populations of interest have
      included adolescents, elderly, minorities, those with comorbid psychiatric or
      substance use disorders, and gender differences. Each group possesses unique
      biological, psychological, and/or social characteristics that confer a
      vulnerability to develop pathological gambling behaviors. Being able to recognize
      those who are at risk to become pathological gamblers is the first step toward
      developing effective prevention and early intervention programs. This is Part Two
      of a three-part series on pathological gambling. Part One appeared in the March
      issue of Psychiatry 2005.

PMID- 21179649
TI  - Evidence for frontal-subcortical circuit abnormalities in bipolar affective
      disorder.
AB  - Most of the literature on bipolar disorder has focused on abnormalities of
      neurotransmitters rather than brain circuits. The few discussions of circuits
      have primarily focused on the limbic system. Evidence is accumulating, however,
      that basal ganglia-thalamic-cortical reentrant circuits play a major role in the
      affective, motor and cognitive symptoms of a number of neuropsychiatric
      conditions including bipolar disorder. In this paper, the authors argue that
      there is compelling direct and indirect evidence of frontal-subcortical circuit
      abnormalities in patients with bipolar affective disorder.

PMID- 21179651
TI  - Use of antipsychotics in the treatment of post-traumatic stress disorder.
AB  - Post-traumatic stress disorder (PTSD) is a severe and disabling psychiatric
      syndrome. With the advent of selective serotonin reuptake inhibitors (SSRIs),
      major strides have been made in the realms of pharmacotherapy. The multiplicity
      of symptom complex includes specific target symptoms, such as intrusiveness,
      aggression, sleep disturbances, and co-existing psychotic symptoms. Consequently,
      atypical antipsychotics gradually have been gaining ground in terms of adjunctive
      utilization. The purpose of this review is to look into the available evidence
      for their adjunctive use in this chronic disorder.

PMID- 21179652
TI  - Augmenting traditional psychotherapy with computer-based technology for a
      selectively mute girl.

PMID- 21179653
TI  - Effective cardiac rehab focuses on burning calories and reducing risks.  New
      research supports the value of walking slower, but longer, among other lifestyle
      changes meant to keep you from developing further heart problems.

PMID- 21179654
TI  - Stroke treatment window widens, but a fast response is still crucial.  Research
      shows the clotbusting drug rt-PA can work if given after four and a half hours,
      but its more effective the sooner it is administered.

PMID- 21179655
TI  - Intensive blood glucose control may lower heart disease risk.  Recent research
      underscores the importance of glycemic control in preventing cardiac events.

PMID- 21179656
TI  - Know the risks when blood pressure is too low. The idea that lower is always
      better when it comes to blood pressure doesn't hold true, especially for patients
      with manifest coronary artery disease.

PMID- 21179657
TI  - Do you need aspirin therapy?  Your risks of heart attack and stroke based upon
      your current and past medical history must be weighed against the chances of
      internal bleeding.

PMID- 21179658
TI  - We hear about arteries getting blocked and needing treatment, but what about
      veins?

PMID- 21179659
TI  - [Medical and psychiatric comorbidity at psychiatric beds in general hospitals: a
      cross-sectional study in Tokyo].

PMID- 21179660
TI  - [Blood levels of brain-derived neurotrophic factor (BDNF) in major depressive
      disorder].
AB  - Brain-derived neurotrophic factor (BDNF) is a neurotrophin that has been linked
      to the viability of neurons in brain circuits that regulate emotion, memory,
      learning, sleep, and appetite. BDNF has been most extensively studied in relation
      to depression. Depressed patients show reduced levels of hippocampal and cortical
      BDNF in postmortem studies. Recently, to the best of our knowledge, there are at
      least three meta-analyses regarding blood BDNF levels in depressed patients,
      suggesting that blood BDNF levels are decreased in depressive state, and those
      are recovered after treatment with biological treatments such as antidepressants,
      ECT, and rTMS. From these findings into account, it is possible that blood
      (plasma and serum) BDNF level is a biological marker for depressive state. We
      have recently demonstrated that a significantly negative correlation was observed
      between the HAMD scores and serum BDNF levels. In addition, responders to
      fluvoxamine, paroxetine, milnacipran, and sertraline all increased serum BDNF
      levels. Blood BDNF levels did not distinguish between responders and remitters to
      the treatment. In conclusion, blood BDNF levels partially reflect those in the
      brain, and there is also strong and consistent evidence indicating that these
      levels normalize following the biological intervention for depression.

PMID- 21179661
TI  - [Epigenetic mechanism of depression].
AB  - Numerous epigenetic studies have revealed that the acetylated status of histone
      as well as methylated status of cytosine is closely involved in gene
      transcription. Preclinical and clinical studies demonstrate that changes in
      levels of various genes in the brain including BDNF, play a role in the
      pathophysiology of depression. It is well known that the levels of BDNF mRNA and
      protein in the rat brain, such as frontal cortex and hippocampus, was decreased
      in response to stress, but the precise mechanism of stress-induced downregulation
      of BDNF has yet to be characterized. In this context, we examined the influence
      of a single immobilization stress (SIS) on the levels of total BDNF mRNA with
      each exon mRNA by real-time PCR and acetylated histone at the promoters of the
      BDNF gene by chromatin immunoprecipitaion assay in the rat hippocampus. SIS
      significantly decreased the levels of total BDNF mRNA with significant reduced
      levels of exon I and IV mRNA. Significant decreases in acetylated histone H3, but
      not H4, were found at the promoters of exons I, IV, and VI. On the other hand,
      antidepressant-like effects has been reported with sodium butylate (SB), a
      histone deacetylase (HDAC) inhibitor, promoting gene transcription. We also found
      antidepressant-like effect of repeated administration of SB in the forced swim
      test using rats. In addition, we found that upregulation in transthyretin mRNA in
      the rat hippocampus is, at least in part, associated with this effect using DNA
      microarray and real-time PCR. Based on these findings, it is postulated that
      epigenetic regulation of the BDNF gene by stress and antidepressants may be
      involved in the pathophysiology of depression.

PMID- 21179662
TI  - [Involvement of neurogenesis in the action of psychotropic drugs].
AB  - Recent studies clearly showed that neurogenesis continued to occur in the certain
      brain regions including hippocampus. The stem or progenitor cells are divided
      equally (proliferation) or unequally, survive apoptosis and differentiate to
      mature neuron and glia. Such newborn cells integrate into existing neuronal
      networks, make synaptic contacts and finally change the plasticity. The
      proliferation is decreased by stress, but chronic treatment of antidepressants
      increases it. We have shown the involvement of cAMP-CREB cascade in mature
      granule cells of dentate gyrus (DG) around stem/progenitor cells in the drug
      action. And to see the direct effect of some psychotropic drugs, we established
      the culture system of adult rat DG-derived neural precursor cell (ADP). Several
      antidepressants did not affect the proliferation. Moreover 5-HT did not promote
      the proliferation of ADPs. On the other hand, noradrenaline and lithium directly
      increase the proliferation. Further investigation is needed to develop new
      antidepressant drugs.

PMID- 21179663
TI  - [A consideration for the mechanism of the transition from depression to
      dementia].
AB  - Epidemiological studies have demonstrated that a history of depression increases
      the risk of developing dementia, in particular Alzheimer's disease (AD). It has
      been suggested that cerebral vascular changes in elderly depression may be a
      biological basis for developing dementia. However, the recent large cohort study
      showed that a history of early-onset depression also increases the risk of
      developing dementia. On the other hand, recent studies have suggested that an
      amyloid protein 40 (A40) to A42 ratio may be associated with the future onset of
      AD. Higher plasma A40/A42 ratio have been reported in elderly depression
      suggesting as a subtype of elderly depression representing a prodromal
      manifestation of AD. To reveal further relationship between depression and AD, we
      compared serum A between patients with major depressive disorder (MDD) and
      healthy controls by age. The result demonstrated that the serum A40/A42 ratio was
      significantly higher in MDD patients than in controls, and this difference was
      seen for both elderly and young subjects. This finding may suggests that even
      young subjects with MDD undergo pathological changes similar to the very early
      stage of AD, and possibly answer the question of why even early-onset depression
      is a risk factor for developing AD.

PMID- 21179664
TI  - [The contributions of psychiatrists to cancer patients].
AB  - In recent years, the Ministry of Health, Labour, and Welfare has promoted the
      dissemination of palliative care services in Japan. In 2006, the Cancer Control
      Act was approved and this law has been implemented since April 2007. Based on
      this law, the Japanese government established the Basic Plan to promote Cancer
      Control Programs. This plan reflected the opinions of cancer patients and their
      families, and aimed to reduce their burdens and improve their quality of life.
      According to the Basic Plan, the Japanese government designated prefectural and
      local cancer hospitals, and required the creation of palliative care teams in
      each designated cancer hospital. The role of palliative care teams is to assess
      the physical, psychological, social, and existential needs of patients with
      advanced illness and their families. On the other hand, the training programs for
      palliative care (Palliative care Emphasis program on symptom management and
      Assessment for Continuous medical Education: PEACE Project) and communication
      skills (SHARE-CST) were developed and implemented. The psychiatrist has a role in
      the education of nonpsychiatric members, especially in the training of palliative
      medicine fellows.

PMID- 21179665
TI  - [Mental care for cancer patients in the clinical practice of consultation-liaison
      psychiatry].
AB  - Psycho-oncology is one of the most important fields of consultation-liaison
      psychiatry (CLP), and it can be said that there is a substantial overlap between
      both fields. In recent years, there has been a particular focus on medical care
      for cancer patients provided by palliative care teams. This type of medical care
      has the following two characteristics from the perspective of the organizational
      theory of CPL. One is that this type of medical care has elements of both medical
      care of a consultation model and medical care of a liaison model. The other is
      that dual team medicine combining team medicine within a palliative care team and
      team medicine between the palliative care team and a primary doctor and floor
      nurses is performed. Such an understanding is important in order to enrich
      medical care provided by palliative care teams in the future. Moreover, in
      clinical CLP, there are some characteristics that are frequently and specifically
      observed in cancer patients. Among those, patients may have a feeling of
      helplessness due to the absence of effective self-care and limitations on the
      ability of the patients to act by themselves. An empowerment approach is
      effective for this, and we have described the actual methods for carrying out
      such an approach.

PMID- 21179666
TI  - [Education for medical professionals who deal with mental care of cancer
      patients].
AB  - With the recent enactment of the Cancer Control Act, mental care for cancer
      patients has become the focus of increasing interest. For the practice of such
      mental care, it is essential not only to depend on psychiatrists but also to
      utilize the collaboration of all healthcare professionals concerned with cancer
      patients, in other words, employ the concept of team medical care. Put in another
      way, it is of prime importance for all healthcare professionals concerned with
      cancer patients to understand the state of mind and psychological aspects of a
      patient and to try to cope with the situation from their respective standpoints,
      in order to maintain and improve the QOL of the patient. Nevertheless, it is not
      uncommon that healthcare professionals not specialized in mental care are
      somewhat at a loss how to identify, understand and cope with the mental problems
      and psychological aspects facing cancer patients. One of the major roles to be
      assumed by psychiatrists for this purpose is to provide knowledge and techniques
      for other healthcare professionals who are involved with cancer patient mental
      care. Effective educational tools currently available for this objective include
      books, the internet and in-service training. However, as tasks for the future,
      training up psychiatrists for the active education of other healthcare
      professionals, the formulation of pertinent educational programs, and
      refurbishing of the relevant educational system are yet to be fulfilled.

PMID- 21179667
TI  - [Essential psychological care in palliative medicine].
AB  - Because of progress in cancer treatment, the development of cancer is not
      necessarily a death sentence. On the other hand, approximately half of patients
      actually die from cancer even today, and many cancer patients require care for
      psychological distress. From the viewpoint of psychiatric diagnosis, the most
      common psychiatric conditions experienced by cancer patients are adjustment
      disorders and/or major depression. From the viewpoint of psychological status,
      however, cancer patients without psychiatric disorders may still suffer from
      fears of recurrence during the survival period and psycho-existential distress or
      death denial during the terminally ill phase. Concerning psychological symptoms
      related to cancer treatment, anticipatory nausea and vomiting is a well
      documented condition among patients receiving high doses of emetogenic
      chemotherapeutic agents. Thus, most cancer patients experience some form of
      psychiatric disorder and/or psychological distress and should receive appropriate
      management and care during the course of their illness. Mental health
      professionals are expected to play a role in managing patients' distress. In
      general, because cancer patients are more likely to prefer psychotherapeutic
      intervention to pharmacological therapy for the management of their distress,
      mental health professionals must rely on psychotherapeutic approaches. Thus,
      mental health professionals need to provide care for cancer patients based on an
      understanding of the course of disease. This review focuses on the psychological
      distress experienced by cancer patients and provides an overview of essential
      psychological care, focusing on psychological interventions for ameliorating the
      psychological distress of cancer patients. Furthermore, the novel system of
      registered psycho-oncologists established by the Japan Psycho-oncology Society to
      foster psycho-oncology professionals who can provide appropriate specialized care
      to cancer patients and/or their families is also introduced.

PMID- 21179668
TI  - [Access to, and exit from, medical treatment for depression: issues related to
      diagnosis and rehabilitation].
AB  - The number of persons in Japan visiting a medical institution for depression in
      2009 exceeded one million, a fact that is attracting particular attention in the
      context of the more than 30000 completed suicides that take place in Japan every
      year. There has never been a time when it was more urgent to address issues
      related to healthcare for depression. While it is true that the consultation rate
      for mood disorders has been increasing annually, it is not known whether this
      reflects an actual increase in the incidence of mood disorders, or whether it is
      simply due to an increase in the number of people seeking treatment. An
      epidemiologic survey of this shift has not been conducted, and therefore accurate
      figures are not available, but a 2002 epidemiologic survey indicated that 74% of
      people experiencing a major depressive episode did not consult a physician. In
      order to promote "entry to treatment" for depression-i.e., early diagnosis and
      early treatment-it is necessary to enhance access to healthcare for those who
      have not consulted a physician. At the same time, if the number of people seeking
      to consult a physician for depression increases from where it currently stands,
      psychiatrists alone will not be able to handle the load. Cooperation with primary
      care physicians and treatment by psychologists will become inevitable. This
      article discusses what information psychiatrists should provide when seeking the
      cooperation of primary care physicians, and also looks at recent research trends
      related to objective indicators, with a focus on NIRS, which are expected to be
      great aids to diagnosis. Concerning "exit from depression," or the reintegration
      of patients into society, major corporations have traditionally been encouraged
      to establish schemes that are primarily supportive in nature, but over the past
      10 years the Ministry of Health, Labour and Welfare has also been promoting other
      measures. One product of these efforts is the "2004 Manual on Workplace Reentry
      Support for Workers Returning from Leave Due to Mental Health Issues," which was
      issued in 2004. This manual was revised and improved in 2009, and highlights the
      significant issue of employees who have taken long leaves of absence, or who have
      left their jobs due to depression, not being accommodated upon their return to
      work. This paper therefore also introduces a number of recent systems that
      support workplace reentry.

PMID- 21179669
TI  - [First record of species Dicranotaenia synsacculata Macko, 1988 (Cestoda,
      Hymenolepididae) of the goldeneye Bucephala clangula (Linneus, 1758) in Poland].
AB  - During parasitological studies of 32 specimens of the goldeneye Bucephala
      clangula L., twenty seven cestode specimens were found. Four of them, isolated
      from the jejunum of two young female hosts, were determinated as Dicranotaenia
      synsacculata Macko, 1988. We based on the shape of cirrus fused with sacculus
      accessorius internus, shape and size of scolex and other organs. This is the
      first record of this species in Poland.

PMID- 21179670
TI  - [Occurrence of parasites in the alimentary canal of cats from Szczecin area,
      Poland].
AB  - The aim of this work was to determine the average prevalence of cats with
      parasites in their alimentary canal in the area of Szczecin and to identify the
      parasite species in the alimentary canal in these animals. This research was
      carried on: domestic cats, stray cats and cats from the Animal Shelter and from
      the Animal Protection Society. Approximately, 3 grams of weight faeces was
      collected, and each sample was homogenized with a glass rod, examined with
      microscope, and then processed by flotation method of Willis-Schlaf. The average
      prevalence of cats with parasites in their alimentary canal was 33.65%. The
      highest prevalence was observed among stray cats (i. e., 57.14%) and among cats
      from the Animal Shelter (i. e., 42.18%); the lowest among domestic cats (i. e.,
      5.68%). The prevalence of infection among cats from the Animal Protection Society
      was 29.62%. The following parasites were observed: Toxocara cati, Toxascaris
      leonina, Dipylidium caninum, Isospora sp. Toxocara cati was the most common
      parasite in cats from the Animal Shelter (i. e., 24.21%) and stray cats (i. e.,
      26.1%). The occurrence of this parasite was lowest among domestic cats (i. e.,
      1.13%). Toxascaris leonina occurred more frequently in domestic cats (i. e.,
      3.4%), while Dipylidium caninum was predominant in cats from the Animal
      Protection Society (i. e., 18.5%). The high prevalence of infections among cats
      from Animal Shelter was caused by the fact that these animals have been rarely de
      wormed. De-worming of animals once a year is not effective. The low prevalence of
      infection among domestic cats can be explained by the facts that these cats were
      routinely de-wormed and had only limited access to outdoor environment. In order
      to prevent transmission of cat parasites it is mandatory to undertake preventive
      actions, such as: regular de-worming of animals, removal animals' faeces, and
      advertisement of de-worming among cat owners by distribution leaflets and
      brochures.

PMID- 21179671
TI  - [Interspecies differentiation of Candida albicans (Robin, 1853) Berkhout, 1923
      strains from multifocal invasions--their identity or similarity parameters].
AB  - The subject of analysis is a pathogenic species of fungi that has the highest
      prevalence in the word--Candida albicans. The aim of this study was to determine
      the identity and similarity of strains for the diagnosis of multifocal
      (concerning two or more organs) invasions. The material was comprised of 210
      strains isolated from 83 women from 6 various ontocenoses: in group I--from the
      vagina, oral cavity and rectum, in group II--from the vagina and oral cavity, in
      group III--from the oral cavity, oesophagus, stomach, duodenum and rectum. Three
      tests were used in this study; API 20 C and API 20 AUX tests were used to
      differentiate interspecies biochemical features, and identify the codes of
      individual strains, while the API ZYM test was used to evaluate extracellular
      hydrolase activity and compare their enzymograms. Strain biotyping was also
      conducted with the use of binomial distribution 1:4:6:4:1. Comparing the codes of
      strains from successive sections of the alimentary tract identified pentafocal,
      tetrafocal, trifocal and bifocal invasions. The analysis of the enzymograms from
      all strains allowed the diagnosis of trifocal and bifocal candidosis. Consecutive
      hydrolase activity and biotyping evaluation demonstrated the similarity of
      strains from various ontocenoses. Interspecies differentiation of Candida
      albicans strains is relevant for the determination of the identity and similarity
      of strains, leading to multifocal infection diagnosis and localization, as well
      as choosing appropriate treatment.

PMID- 21179672
TI  - [The last data concerning fungal, bacterial and viral infections after cell,
      tissue and organ transplantations and other problems concerning mycology and
      parasitology presented at 49th Clinical Day of Medical Parasitology].

PMID- 21179673
TI  - [Digital diagnosis and treatment system for facial prostheses].
AB  - Conventional diagnosis and treatment for facial prostheses have setbacks and
      limitations, including complicated procedure, inefficiency, low accuracy and poor
      esthetics, which could not meet the demand for high quality of the prostheses of
      the patients. With the technology of the computer aided design and computer aided
      manufacture (CAD/CAM), the new era for diagnosis and treatment for facial
      prostheses has been started since the 1990's. The digital diagnosis and treatment
      system for facial prostheses has been formed during these ten years, which
      including the digital data acquisition of the facial defect, CAD for facial
      prostheses, rapid fabrication of the prostheses. This new system will be the
      development direction and mainstream technology in the future.

PMID- 21179674
TI  - [Study on osteogenic ability of chitosan/beta-tricalcium phosphate scaffold
      combined with human bone morphogenetic protein].
AB  - OBJECTIVE: Using chitosan (CS)/beta-tricalcium phosphate (TCP)/recombinant human
      bone morphogenetic protein (rhBMP)-2 for the reconstruction of rabbits' mandible
      defect, to prove the feasibility of CS/beta-TCP as an injectable bone tissue
      engineering scaffold material. METHODS: Twenty-four New Zealand white rabbits
      were randomized into 4 groups on average: Experimental group 1 embedding CS/beta
      TCP/rhBMP-2, experimental group 2 embedding CS/ beta-TCP, control group 1
      embedding autograft bone group, control group 2 embedding nothing. At 2, 4 and 8
      weeks after surgery, all rabbits were executed group by group. The new bone
      growth situations were observed with hematoxylin-eosin staining and
      immunofluorescence microscopy, the bone mineral density was detected by bone
      sonometers. RESULTS: After 2, 4, 8 weeks, there was significant difference among
      the areas of bone regeneration of all groups. The effect of experimental group 1
      was better than experimental group 2. There was significant difference at
      different times, the areas of bone regeneration was gradually increased with
      time. The area of stained yellow in experimental group 1 was larger, the area of
      stained red was smaller. The quantities of bone density in experimental group 1
      at every time after surgery were significantly higher than experimental group 1
      and control group 2, but had no statistical significance with control group 1.
      CONCLUSION: CS/beta-TCP/rhBMP-2 has good biocompatibility, degradability and the
      capacity of guided and inducing osteogenesis. CS/beta-TCP as a good injection of
      carrier could become a promising carrier for rhBMP-2 and potential new degradable
      biological material for repairing bone defect in clinical application.

PMID- 21179675
TI  - [Expression of CD133+ endothelial progenitor cell in rat periodontal tissue
      during tooth movement].
AB  - OBJECTIVE: To investigate the expression patterns of CD133+ endothelial
      progenitor cell (EPC) on Wister rats during experimental tooth movement. METHODS:
      40 Wistar rats' teeth movement models were established and divided into
      experiment group and control group. After loading 1, 3, 5, 7, 14 days killed them
      respectively. The histological sections were stained with hematoxylin-eosin and
      rabbit anti-rat CD133 polyclonal antibody to express CD133 immunoreactivity.
      RESULTS: Expression of CD133 in the new vessels did not appear in control group.
      In the early experiment, the expression of CD133 was discovered in the new
      vascular endothelial cells of periodontium in experiment group. Expression of
      CD133 got the maximum after loading 1 day in experiment group, then decreased
      gradually, but it was not significantly higher than control group (P > 0.05).
      CONCLUSION: CD133+ EPC participated vascularized reaction in periodontal tissue
      of rat during the experimental tooth movement, direct participation was few and
      indirect effects possibly existed.

PMID- 21179676
TI  - [Torque resistance of three different types of nickel-titanium rotary
      instruments].
AB  - OBJECTIVE: To compare torsional fracture of three different types of nickel
      titanium rotary instruments ProTaper, Hero642 and Mtwo by making a stimulate
      models in vitro. METHODS: Through the establishment of model in vitro, compared
      the different time with 3 kinds of nickel titanium file in cutting-edge bound
      occurs, and to observe the section of fractured instruments by scanning electron
      microscope. RESULTS: The resistence to torque was different from three types of
      nickel titanium instruments. The time to fracture of Mtwo was significantly
      longer than ProTaper's and Hero642's, but ProTaper's and Hero642's had no
      significant difference. Three kinds cross-sectional design were different, a lot
      of toughness nests were seen in broken surface. Most of them were ductile
      fracture. Time to fracture was influenced by the quality disfigurement.
      CONCLUSION: The resistance to torque of Mtwo was better than ProTaper and
      Hero642. The lifespan was influenced by the design of cross-section. The quality
      disfigurement of the files reduced the resistance to flexual fatigue.

PMID- 21179677
TI  - [Suppression to ameloblastoma xenografts of chicken embryo chorioallantoic
      membrane by tissue inhibitor of metalloproteinases-2].
AB  - OBJECTIVE: To explore the invasiveness of xenografts on chicken embryo
      chorioallantoic membrane (CAM) after tissue inhibitor of metalloproteinase-2
      (TIMP-2) gene transfection. METHODS: Fresh ameloblastoma tissues were minced into
      1-2 mm3 and transplanted on the CAM. There were three groups named as control
      group (Empt), plasma transfection group (Lipo), and TIMP-2 gene transfection
      group (P). The specimens were respectively investigated by microscope indifferent
      spots after implanting. The volume of the xenografts and the weight of xenografts
      in the termination time of the experiment were recorded. The invasiveness of
      xenografts was divided into four grades by pathological examination. Western blot
      analysis was performed to investigate matrix metalloproteinase-2 (MIMP-2) and
      TIMP-2 protein in xenografts. RESULTS: Ameloblastoma tissues can survive on CAM
      and the tumor cells may invade it on 5-7 days after implanting. At 9 d after
      implanting, the invasiveness grades in P group were 7 in grade 0, 1 in grade 2, 0
      in grade 3. The expression of TIMP-2 protein in P group was significantly higher
      than that in Empt group (P < 0.05). The expression of MMP-2 protein in P group
      was lower than that in Empt group (P < 0.05). CONCLUSION: The xenotransplanted
      tumor model of human ameloblastoma on CAM was successfully established. The
      invasiveness of ameloblastoma xenografts was suppressed might be due to TIMP-2
      gene transfection.

PMID- 21179678
TI  - [The activation of p38MAPK in hypoglossal necleus and the effect of nerve growth
      factor on regeneration following hypoglossal nerve crush in rat].
AB  - OBJECTIVE: To explore the activation of phospho-p38 mitogen activated protein
      kinases (p-p38MAPK) and to evaluate the possible role of nerve growth factor
      (NGF) on neuronal protection and regeneration of injured nerve in a model of
      hypoglossal nerve injury in rats. METHODS: Sixty healthy adult SD rats were
      divided randomly into three groups: NC control group, NS control group and NGF
      treatment group. The rats were allowed to survive for 1, 3, 5, 7 and 14 days
      after operation respectively. Frozen sections were processed for
      immunohistochemistry (IHC) to decide the p-p38MAPK expression level in the
      motoneurons of hypoglossal nucleus. Nissi's staining was used to evaluate
      cellular morphological and architectural changes in the hypoglossal nucleus.
      Transmission electron microscope (TEM) study was employed to investigate the
      subcellular structural alternations of the hypoglossal nerve distal to the injury
      site. RESULTS: The expression level of p-p38MAPK was low in NC group and elevated
      in all operated animals. However, p-p3SMAPK immunoreactivity in the hypoglossal
      motoneurons in NGF group was lower than NS control group after injury. The
      survival rate of motoneurons in hypoglossal nucleus of injured side in NGF group
      was higher than that in NS group. Ultrastructural study revealed more
      regenerating myelinated axons which distributed homogenously in the distal site
      of the lesioned hypoglossal nerve from the NGF group than NS group. CONCLUSION: p
      p38MAPK was slightly expression in normal hypoglossal nucleus but intensively
      expression after injury. NGF can down-regulate p-p38MAPK expression in the
      motoneurons of hypoglossal nucleus after hypoglossal nerve was crushed. Exogenous
      NCF can protect damaged neurons and promote nerve regeneration after hypoglossal
      nerve crush injury in rats.

PMID- 21179679
TI  - [The effect of firing times on the chroma of tetragonal zirconia polycrystal by
      adding rare-earth oxides].
AB  - OBJECTIVE: The aim of this study is to evaluate whether the firing times affect
      the chroma of zirconia by adding rare-earth oxides. METHODS: Six kinds (S1, S2,
      S3, S4, S5, S6) of tooth-like yttria stabilized tetragonal zirconia polycrystal
      (Y-TZP) were available by introducing internal colorating technology, the color
      were gauged with ShadeEye NCC chromatometry instrument, and one-way ANOVA was
      used to analysis the color of each kind of tooth-like zirconia after 1, 2, 3, 4,
      5 times firing individually. RESULTS: After 1, 2, 3, 4, 5 times firing
      respectively, the chromatic aberration ranged between 0.10-1.47 merely. The
      luminosity of three kinds (S1, S2, S6) of tooth-like zirconia were decreased (P <
      0.05), the luminosity of the other three kinds (S3, S4, S5) of tooth-like
      zirconia were not obviously changed (P > 0.05), as for the hue and chroma, no
      significant differences were found (P > 0.05). CONCLUSION: There are no
      significant influence on the color of tooth-like Y-TZP after 1, 2, 3, 4, 5 times
      firing respectively, the chroma of yttria stabilized tetragonal zirconia
      polycrystal by adding rare-earth oxides are with high stability.

PMID- 21179680
TI  - [The effect of basic fibroblast growth factor on the mRNA expression of beta1
      integrin subunit by periodontal ligament fibroblasts in culture].
AB  - OBJECTIVE: To study the effect of basic fibroblast growth factor on the mRNA
      expression of beta1 integrin subunit by periodontal ligament fibroblasts in
      culture; to discuss the effect of basic fibroblast growth factor in periodontal
      regeneration. METHODS: Human periodontal ligament fibroblasts were cultured and
      stimulated by basic fibroblast growth factor (0.1, 1.0, 10.0 ng x mL(-1)) for 24,
      48, 72 h respectively, and then mRNA expression of beta1 integrin subunit was
      assessed by fluorescent quantitative real-time reverse transcription polymerase
      chain reaction. RESULTS: Basic fibroblast growth factor enhanced the mRNA
      expression of beta1 integrin subunit, and there was optimal effect when the
      concentration of basic fibroblast growth factor was 1.0 ng x mL(-1) at 24, 48, 72
      h respectively; the mRNA expression of beta1 integrin subunit at 72 h was higher
      than that at 24, 48 h. CONCLUSION: Basic fibroblast growth factor can strengthen
      human periodontal ligament fibroblasts' adhesion and may be one of important
      factors which participate in the periodontal regeneration.

PMID- 21179681
TI  - [Preliminary investigation about incisor inclination and dental compensation of
      normal occlusion and angle's class II division 1 malocclusion with different
      growth patterns].
AB  - OBJECTIVE: To investigate characteristics of incisors inclination and dental
      compensation in normal occlusion and Angle's Class II division 1 malocclusion
      with different growth patterns. METHODS: 158 cephalometric films of normal
      occlusion and 246 cephalometric films of Angle's Class II division 1 malocclusion
      were selected and the data of relevant variables were compiled to analyze the
      inclination of incisors. RESULTS: The upper and lower incisors were lingually
      inclined in normal occlusion with vertical growth pattern while labially inclined
      in horizontal growth pattern. Compared with the average value of normal occlusion
      with different growth patterns, the upper incisors of Class II division 1
      malocclusion were relatively labially inclined in different growth patterns and
      the lower incisors were labially inclined in vertical and average growth
      patterns, while there were no obvious changes in horizontal growth pattern.
      CONCLUSION: When treating patients with Angle's Class II division 1 malocclusion,
      we should choose a specific method according to patients' growth patterns and
      characteristics of dental compensation.

PMID- 21179682
TI  - [The analysis of lip contour of class II division 1 malocclusion in the early
      permanent dentition].
AB  - OBJECTIVE: To study the lip contour of Class II division 1 malocclusion in the
      early permanent dentition with different growth patterns and gender. METHODS: 145
      patients with Class II division 1 malocclusion in the early permanent dentition
      were included in this study. Their pre-treatment cephalometric X-rays were
      measured to analyze the influence of gender and growth pattern on the lateral lip
      contour. One-way analysis of variance was used to analyze the influence of growth
      pattern on the lip contour of patients in the early permanent dentition, and t
      test was used to analyze the influence of gender on the lip contour of patients.
      RESULTS: The lip vertical extension values of male patients were larger than that
      of female (P < 0.05); the lip sagittal extension value of male seems to be larger
      too, but no significant difference was found (P > 0.05). The upper lip extension
      patterns of patients with different growth patterns were the same, but patients
      of horizontal growth pattern had more everted and protrusive lower lips than
      patients of vertical growth pattern. CONCLUSION: Gender and growth pattern both
      have influences on the lip contour of Class II division 1 malocclusion in the
      early permanent dentition.

PMID- 21179683
TI  - [Relationship between beta amyloid protein 1-40 and post-operative delirium after
      oral and maxillofacial surgery in elderly patients].
AB  - OBJECTIVE: To determine the incidence of post-operative delirium after oral and
      maxillofacial surgery under general anesthesia in elderly patients, and to
      examine its association with plasma concentrations of beta amyloid protein 1-40
      (Abeta1-40). METHODS: Fifty patients underwent elective oral and maxillofacial
      surgery were divided into two groups: Group C (n=20) aged from 20 to 60 years
      old, and Group T (n=30) aged from 62 to 78 years old. The two group received the
      same general anesthesia. Delirium rating scale-revised-98 (DRS-R-98) was used as
      an instrument to diagnose and access the postoperative delirium of the two
      groups. The scores of DRS-R-98 were recorded before operation (T0) and at 24 h
      (T1), 48 h (T2), 72 h(T3) and 96 h(T4) after the operation. Serial measurements
      of serum concentrations of Abeta1-40 were also performed at the same time.
      RESULTS: The incidence of post-operative delirium after oral and maxillofacial
      surgery in Group T was 20.0%. The concentrations of plasma Abeta1-40 in group T
      were much higher than group C at TO, T1, T2 and T3 significantly (P < 0.01). The
      concentrations of plasma Abeta1-40 at T1 and T2 were higher than those at TO in
      the same group (P < 0.05). The scores of DRS-R-98 in Group T at T3 and T4 were
      much higher than those at T1 and Group C significantly (P < 0.01). CONCLUSION:
      The constant increase of plasma Abeta1-40 may be one of the important factors
      related to post-operative delirium in elderly patients underwent oral and
      maxillofacial surgery.

PMID- 21179684
TI  - [Comparative effects of the maltitol chewing gums on reducing plaque].
AB  - OBJECTIVE: To estimate the clinical effect of the maltitol chewing gums in plaque
      control. METHODS: Thirty 13-15 years old susceptible adolescent were divided into
      three groups randomly, group A (maltitol chewing gums), group B (xylitol chewing
      gums) and group C (gum base chewing gums). Subjects chewed gums 5 times each day,
      10 min each time. At baseline and at 4-week, subjects were evaluated for
      supragingival plaque. SPSS 17.0 software package was used for statistical
      analysis. RESULTS: Four weeks later, plaque index of the three groups
      continuously step down. Significant difference was observed between baseline and
      4-week (P = 0.000, 0.000, 0.006). Four weeks later, there was statistically
      significant difference in clearance rate of plaque among the three groups (P =
      0.015). There was still no statistically significant difference between group A
      and group B (P = 0.687), but they were both different from C group(P = 0.019,
      0.007). CONCLUSION: Maltitol chewing gum can lead to similar effect on reduction
      of plaque as xylitol chewing gum.

PMID- 21179685
TI  - [The effect of the metallic dental materials on magnetic resonance imaging].
AB  - OBJECTIVE: To explore the influence of conventional metal materials in oral
      cavity on brain magnetic resonance imaging (MRI). METHODS: Four kinds of metal
      materials (metal ligature wire, forging hard and slotless denture, casting
      nichrome denture, casting copper alloy denture) in oral cavity were scanned
      through MRI. FSE sequence T1 weighted imaging (FSE T1), EPI diffusion-weighted
      imaging (DWI) sequence of ordinary, Propeller DWI imaging were used. RESULTS: In
      FSE T1 sequence, metal ligature wire and forging hard and slotless denture
      produced serious false image, casting nichrome denture produced moderate false
      image, casting copper alloy denture produced only little false image. In EPI DWI
      sequence, obvious magnetic-sensitive false image were produced in the dissection
      tissue of the brain by metal ligature wire. While in Propeller DWI sequence,
      magnetic-sensitive false image were greatly reduced and satisfactory images were
      formed. CONCLUSION: Different metal materials in oral cavity have different
      influence on the MRI. The false images produced by different metal materials are
      closely related to the type of the material. Magnetic-sensitive false images can
      be eliminated by Propeller DWI technique.

PMID- 21179686
TI  - [Effect of laser surface hardening technology on the corrosion resistance of
      dental casting alloy].
AB  - OBJECTIVE: To investigate the effect of the laser surface hardening technology on
      the corrosion resistance of dental casting alloy. METHODS: Twenty-three cobalt
      chromium alloy specimens were made in this study. Twenty-two specimens were
      equally divided into two groups randomly. One was experimental group for laser
      surface hardening processing and the other was control group without any
      treatment. In each group, ten specimens were used for corrosion analysis by
      electrochemical method, and one for surface metallographical structure and
      morphology observation by scanning electron microscope. Remaining one specimen
      was partially processed on limited area for surface metallographical structure
      and morphology comparison. RESULTS: Metal grains distributed uniformly and
      achieved a good refinement with mainly the same size in experimental group. Metal
      grains in specimen which processed in its partial surface area also achieved a
      good refinement in the laser processing area. There was statistical difference in
      electric potential of corrosion and logarithmic value of current of corrosion
      between experimental group and control group (P < 0.01). CONCLUSION: Laser
      surface hardening technology has a positive effect in improving the corrosion
      resistance of dental casting alloy in artificial saliva.

PMID- 21179687
TI  - [Assessment research on the inter-proximal mesial papilla height of single
      implant-supported maxillary central incisor].
AB  - OBJECTIVE: This prospective study was to observe the correlation between the
      mesial papilla's height of single implant-supported maxillary central incisor and
      the distance from the base of the contact point to the alveolar bone crest.
      METHODS: 56 patients involved in single implant-supported maxillary central
      incisor were included in this study. The distances from the base of the contact
      point to the alveolar bone crest in the digital periapical film of maxillary
      central incisor were measured using the software Planmeca Dimaxis Version 3.3.2.
      The time of measurements were as follows: The pre-surgical and post-surgical
      periods, before and after the crown installation, the follow-up examination of
      more than 0.5 year. To analyze the factor of influencing distance, and the
      correlation between the distance and the height of gingival papilla during the
      whole restored period. Correlation analysis between the distance and the height
      of gingival papilla during the whole restoration was done by the statistical
      software SPSS 12.0. RESULTS: The results demonstrated that the ratio of esthetic
      papilla can achieve 54.5% at the crown installation and 95.5% at the follow-up
      examination when the distance was between 3 mm and 5 mm. When the distance was
      between 5 mm and 6 mm, they dropped to 30.0% and 75.0%, respectively. However,
      when the distance increased to above 7 mm, the papilla could hardly be in an
      esthetic outcome. There was a significant change of the distance was found during
      the periods from the post-surgery to pre-restoration, and the scope of the
      changes was between -0.13 mm and 0.46 mm. A negative correlation was found
      between the distance and the index of papilla. The correlation coefficient r was 
      0.715 (P < 0.01). CONCLUSION: It is proposed that the pre-surgery distance of
      maxillary central incisor from the base of the contact point to the alveolar bone
      crest can be used as one of the important reference indexes to assess and predict
      the height conditions of gingival papilla.

PMID- 21179688
TI  - [Accuracy evaluation of computer aided design and computer aided manufacture
      template for implant placement].
AB  - OBJECTIVE: The computer aided design and computer aided manufacture (CAD/CAM)
      template was fabricated basing on CT data of completely edentulous jaws, and the
      accuracy of template was evaluated by assessment of the deviation between the
      actual and planning position of the implant after the registration of pre- and
      post-operative CT images. METHODS: The CAD/CAM templates for 4 completely
      edentulous jaws were designed and fabricated basing on the pre-operative CT data
      and the stone models of the jaws sample. And 14 implants were placed in the
      posterior region of the jaws aided by the CAD/CAM template. The pre- and post
      operative CT was registered by the point to point method, and the deviation
      between actual and virtual implants was measured to assess the accuracy of the
      template. RESULTS: With the aid of CAD/CAM template, the deviations of the
      position at the tail of the implant, at the tip of the implant and the projected
      deviation of angle were (0.19 +/- 0.07) mm, (0.47 +/- 0.12) mm, and 1.790 +/-
      0.68 degrees respectively, and the deviations of the position at the bucco
      palatal, disto-mesial, vertical direction were (0.22 +/- 0.08) mm, (0.25 +/-
      0.06) mm, (0.30 +/- 0.11) mm at the tip respectively. CONCLUSION: Within the
      limits of this study, the results verify the accuracy of CAD/CAM template and
      support its use for safety implant placement.

PMID- 21179689
TI  - [Repairing effects of low-intensity pulsed ultrasound on alveolar bone defects in
      Beagle dogs].
AB  - OBJECTIVE: To evaluate the potential repairing effects of low-intensity pulsed
      ultrasound (LIPUS) irradiation on acute horizontal alveolar bone defects at the
      mandibular pre-molar areas in Beagle dogs. METHODS: Horizontal alveolar bone
      defect models were established under enamelo-cemental junction 6 mm at the
      mandibular third and forth pre-molar buccal regions on both sides in 4 beagle
      dogs, and bilateral sides of each dog were randomly divided into two groups:
      Experimental groups with LIPUS irradiation (I(SATA) 30 mW X cm(-2), 20 min x d(
      1)) and control groups without opening power source of LIPUS radiation. Dual
      energy X-ray bone densitometer was used to detect the bony density after an 8
      weeks' irradiation. Meanwhile, decalcified bone tissue sections were used to
      assess the histological effects of new alveolar bone. RESULTS: The results of new
      bony density detection in experimental group and control group were (0.6053 +/-
      0.0566) g x cm(-2), (0.6047 +/- 0.0552) g x cm(-2), respectively, and there was
      no statistical significance between the differences of the two groups (P =
      0.9839). Hematoxylin-eosin staining of decalcified bone tissue sections
      demonstrated that there were more osteoblasts lining at the edge of new alveolar
      bone in the experimental groups than that scattered in the control groups, and
      Masson staining revealed that collagens in new alveolar bone stained bright red
      indicating higher maturity in the experimental groups, while in the control
      groups mainly stained blue with some virescent areas indicating lower maturity.
      CONCLUSION: LIPUS irradiation on acute horizontal alveolar bone defects has
      potential repairing effects.

PMID- 21179690
TI  - [Root resection by Er:YAG laser: a scanning electron microscope study].
AB  - OBJECTIVE: To compare the difference of the surface of root resection by Er:YAG
      laser, ultrasonic or high-speed handpiece with scanning electron microscope
      (SEM), and to evaluate the possibility of using Er:YAG laser on the root
      resection in clinical application. METHODS: Thirty maxillary central incisors
      were divided into three groups (Er:YAG laser group, ultrasonic group, high-speed
      handpiece group), and the root resection were made at root tip 3 mm with Er:YAG
      laser, ultrasonic instrument or long needle diamond bur according to grouping.
      The surface of the root resection by SEM in the aspects of debris, smear layer,
      opened dentinal tubules, cracks and ablation characteristics were compared.
      RESULTS: The examination revealed that Er:YAG laser group and ultrasonic group
      had no or little debris and smear layer and with opened dentinal tubules. High
      speed handpiece group had great amount of debris and smear layer and without
      opened dentinal tubules. Cracks were observed in ultrasonic group and high-speed
      handpiece group, no in Er:YAG laser group. There were ablation characteristics in
      ultrasonic group and high-speed handpiece group, but no in Er:YAG laser group.
      CONCLUSION: From the morphological aspect, Er:YAG laser has much more advantage
      than ultrasonic instrument and diamond bur for the root resection.

PMID- 21179691
TI  - [Comparison of color reappearance between metal-ceram restoration and foundry
      ceram restoration using crystaleye spectrophotometer].
AB  - OBJECTIVE: To study the color reappearance effect of metal-ceram restoration and
      foundry-ceram restoration using Crystaleye spectrophotometer. METHODS: 58 metal
      ceram restorations and 58 foundry-ceram restorations according to the result of
      the Crystaleye spectrophotometer were made respectively. The deltaE between
      restorations and natural teeth as referenced were analyzed. And satisfaction of
      dentists and patients were evaluated. RESULTS: The deltaE between metal-ceram
      restorations and natural teeth was 7.13 +/- 0.74. The deltaE between foundry
      ceram restorations and teeth was 1.47 +/- 0.84. There were statistical
      differences between the deltaE (P < 0.01). The satisnatural faction of dentists
      and patients to the foundry-ceram restorations were higher than to the metal
      ceram restorations (P < 0.05). CONCLUSION: Crystaleye spectrophotometer can
      provide accurate reference for foundry-ceram restoration, but for metal-ceram
      restoration it is not accurate.

PMID- 21179692
TI  - [PTEN tumor suppressor gene combined with doxycycline inhibites telomerase
      activity in human mucoepidermoid carcinoma cell line].
AB  - OBJECTIVE: To investigate the effect of PTEN tumor suppressor gene combined with
      doxycycline on telomerase activity in human mucoepidermoid carcinoma cell line.
      METHODS: The wild-type PTEN tumor suppressor gene or empty vector was introduced
      into mucoepidermoid carcinoma cell line in vitro, then the cancer cells were
      treated with doxycycline. Cancer cell survival was determined by MTT assay.
      Telomerase activity was determined using telomerase repeat amplification protocol
      enzyme-linked immunosorbent assay (TRAP-ELISA). RESULTS: Compared to the control
      cells, cancer cells transfected with the wild-type PTEN gene showed growth
      inhibition and increased sensitivity to doxycycyline, and the ratio of augment of
      drug sensitivity was 1.65-4.75. The telomerase activity in cancer cells treared
      with PTEN gene transfection or doxycycline alone decreased, however, telomerase
      activity in combined group decreased more remarkably. CONCLUSION: PTEN gene in
      combination with doxycycline has significant inhibitory effect on telomerase
      activity in cancer cells.

PMID- 21179693
TI  - [Analysis of relationship between the detection of Enterococcus faecalis in post
      treatment endodontic disease and clinical symptom or sign].
AB  - OBJECTIVE: To detect the Enterococcus faecalis (E. faecalis) in post-treatment
      endodontic disease, and to analyze the relationship between the occurrence of E.
      faecalis and clinical symptom. METHODS: 108 teeth which need root canal
      retreatment were collected, and the clinical symptoms and physical signs were
      recorded. Bacterium samples from root canal were taken, and genome DNA from
      bacterial samples were extracted. The occurrence of E. faecalis by means of the
      polymerase chain reaction was investigated. RESULTS: The detection rate of E.
      faecalis in cases of root canal retreatment was 47.2%, while in cases with
      symptoms or signs, or cases with both symptoms and signs, the root canal E.
      faecalis detection rates were 52.6%, 57.9%, 62.5%. The detection rates of E.
      faecalis between cases with clinical symptom and without clinical symptom
      demonstrated statistical significance (P < 0.05). The detection rates between
      cases with both clinical symptom and manifestly aneretic root and cases without
      clinical symptom and manifestly aneretic root had statistical significance (P <
      0.05). In the group of clinical symptom, the detection rate of E. faecalis in
      cases with biting pain was 66.7%, clearly higher than those without biting pain
      (P < 0.05). CONCLUSION: The occurrence of E. faecalis in cases of root canal
      retreatment correlates with clinical symptoms.

PMID- 21179694
TI  - [Role of protein kinase C-delta in hyperthermia-induced apoptosis in tongue
      squamous cell carcinoma Tca8113 cells].
AB  - OBJECTIVE: To study the role of protein kinase C-delta (PKC-delta) in
      hyperthermia-induced apoptosis in human tongue squamous cell carcinoma Tca8113
      cells. METHODS: Tca8113 cells were treated at 43 degrees C in a heating water
      bath for 0, 40, 80, 120 min after pretreatment with Rottlerin, a specific
      inhibitor of PKC-delta, and equal volume dimethyl sulfoxide (DMSO) for 30 min,
      respectively. The cells were stained by propidium iodide (PI) and Rhodamine 123
      to analysis apoptotic rate and the changes of mitochondrial transmembrane
      potential by flow cytometry (FCM). The total proteins were extracted for Western
      blotting analysis of activation and proteolysis of PKC-delta, and for
      colorimetric assay of relative activity of Caspase-3. RESULTS: Hyperthermia could
      induce proteolysis and activation of PKC-delta, and this was attenuated by
      Rottlerin. Apoptotic rate, decreasing of mitochondrial transmembrane potential
      and activity of Caspase-3 which being induced by hyperthermia in Tca8113 cells
      were inhibited by PKC-delta specific inhibitor Rottlerin. There were
      significantly statistical differences in apoptosis rates, mitochondrial
      transmembrane potential and activity of Caspase-3 between Rottlerin- and non
      Rottlerin-pretreated cells after hyperthermia for 40, 80, 120 min (P < 0.01).
      CONCLUSION: Activated PKC-delta may facilitate hyperthermia-induced apoptosis in
      Tca8113 cells, and may be one of the mechanisms of apoptosis induced by
      hyperthermia.

PMID- 21179695
TI  - [Influence of deposition time on chromatics during nitrogen-doped diamond like
      carbon coating on pure titanium].
AB  - OBJECTIVE: The aim of this study was to observed the influence of deposition time
      on chromatics during nitrogen-doped diamond like carbon coating (N-DLC) on pure
      titanium by multi impulse are plasma plating machine. METHODS: Applying multi
      impulse are plasma plating machine to produce TiN coatings on pure titanium in
      nitrogen atmosphere, then filming with nitrogen-doped DLC on TiN in methane (10
      80 min in every 5 min). The colors of N-DLC were evaluated in the CIE1976 L*a*b*
      uniform color scale and Mussell notation. The surface morphology of every
      specimen was analyzed using scanning electron microscope (SEM) and X-ray
      photoelectron spectroscopy (XPS). RESULTS: When changing the time of N-DLC
      coating deposition, N-DLC surface showed different color. Golden yellow was
      presented when deposition time was 30 min. SEM showed that crystallization was
      found in N-DLC coatings, the structure changed from stable to clutter by varying
      the deposition time. CONCLUSION: The chromatics of N-DLC coatings on pure
      titanium could get golden yellow when deposition time was 30 min, then the
      crystallized structure was stable.

PMID- 21179696
TI  - [Expression of Ki67 and P53 proteins in gingival tissue after wearing casting
      alloy crowns].
AB  - OBJECTIVE: The aim of the study was to detect the expression of Ki67 and P53
      proteins in the gingival tissue before and after wearing three kinds of dental
      casting alloy crowns. METHODS: The three kinds of dental casting alloys (58%
      golden alloy, NiCr alloy, NiCr alloy excluding Be) were used to make full crowns
      for 3 dogs in each group. Another 3 dogs were taken as control. The
      immunohistochemistry Envision method was used to measure the expression of Ki67
      and P53 proteins in the gingival tissue before wearing the crowns, 2 weeks, 1
      month, 2 months, 3 months after wearing the crowns. RESULTS: The expression of
      Ki67 and P53 proteins in gingival tissue increased 1 month after wearing NiCr
      alloy and NiCr alloy excluding Be, then decreased gradually. And the expression
      of Ki67 and P53 proteins in 58% golden alloy group was similar to that in
      control. No pathological change was observed in all samples. CONCLUSION: Two
      kinds of NiCr alloy crowns both can increase the expression of Ki67 and P53
      proteins in gingival tissue, but 58% golden alloy crowns can not. So compared
      with NiCr alloy crowns, 58% golden alloy crowns have better biological
      properties. And none of three kinds of dental alloy crowns may induce long-term
      abnormal proliferation in gingival tissue.

PMID- 21179697
TI  - [Effects of dexamethasone and vitamin B12 on expression of fibroblast growth
      factor 10 and fibroblast growth factor receptor 2b during early palatogenesis].
AB  - OBJECTIVE: To observe the alteration of fibroblast growth factor 10 (Fgf10) and
      fibroblast growth factor receptor 2 (Fgfr2b) signal in mouse embryonic palate
      after dexamethasone and vitamin B12 exposure. METHODS: Dams were divided
      teratogenetic group, antagomistic group and control group and were respectively
      injected dexamethasone, dexamethasone and vitamin B12, and normal sodium. Dams
      were killed and fetus was collected at embryo 12.5 and 13.5 day. The expression
      of Fgf10 and Fgfr2b and mesenchymal cells proliferation of mouse embryonic by
      western blotting and BrdU assay were checked. RESULTS: Fgf10 and Fgfr2b
      expression was down-regulated and mesenchymal cells proliferation was inhibited
      significantly after dexamethasone exposure. After vitamin B12 treatment, Fgf10
      and Fgfr2b expression did not restore, but cells proliferation was recovered.
      CONCLUSION: Dexamethasone and vitamin B12 affected the expression of Fgf10 and
      Fgfr2b of mouse embryonic palate and mesenchyme cells proliferation, but the
      change was disaccord.

PMID- 21179698
TI  - [Effect of astragalus membranaceus on the proliferation, osteogenic capacity and
      structure of periodontal ligament cells in vitro].
AB  - OBJECTIVE: To investigate the effect of Astragalus membranaceus (APS) on the
      proliferation, osteogenic capacity and structure of periodontal ligament cells
      (PDLCs) in vitro. METHODS: PDLCs were cultured in vitro with APS of 0.08, 0.1,
      0.2, 0.4 mg x mL(-1). Methyl thiazolyl tetrazolium (MTr), alkaline phosphatase
      (ALP) and cell structure were detected to determine the proliferation and
      differentiation of PDLCs proliferation and differentiation. RESULTS: When the APS
      was 0.2 mg x mL(-1), the absorbance of MTT and ALP exhibit significantly
      increased as compared to the control (P < 0.05). The cells cultured in vitro with
      APS of 0.2 mg x mL(-1) had the normal structure. CONCLUSION: APS with proper
      concentration in short-term culture may promote the proliferation and
      differentiation of PDLCs.

PMID- 21179699
TI  - [Biological characteristics of CD133+ subpopulation in tongue squamous cell
      carcinoma Tca8113 cell line].
AB  - OBJECTIVE: To detect the expression of CD133 in human tongue squamous cell
      carcinoma Tea8113 cell line and observe proliferation ability of CD133 groups in
      vitro. METHODS: Limiting dilution assay was employed to observe the proliferating
      character of Tca8113 single cell in vitro. The ability of growing as cancer
      spheroids was observed with ultra-low attachment plates. The flow cytometry was
      used to detect the expression of putative tumor-initiating cell marker CD133 in
      human tongue squamous cell carcinoma Tca8113 cell line. The selective technique
      of immunomagnetic beads was applied to purify CD133 tumor cells, CD133 tumor
      cells were cultured and their ability of proliferation were observed in vitro.
      RESULTS: After 12 days, the result of single cell culture in vitro revealed that
      about 5.23% of cultured Tca8113 cells possessed the capacity of continue
      proliferation. The cells line fromed floating clusters with one week of passaging
      cells into non-adherent plates. Approximately 0.95% of cells in Tca8113 cell line
      expressed CD133. Compared with CD133- cells and control Tca8113 cells, CD133+
      cells demonstrated increased proliferation capacity. The proportion of CD133
      cells decreased in culture as days passed. The percentage of CD133+ cells
      decreased from 92.45% to 1.62% in twelve days' culture. CONCLUSION: Tumor stem
      cells have the character of heterogenity and lower proportion of CD133 but higher
      ability of proliferation, and the diferentiation in human tongue squamous cell
      carcinoma Tca8113 cell line in vitro, CD133 may be one of makers for tumor
      initiating cell of human tongue squamous cell carcinoma Tca8113 cell line.

PMID- 21179700
TI  - [Purification of mutacin].
AB  - OBJECTIVE: To purify mutacin produced from isolated Streptococcus mutans (S.
      mutans) strains in order to, contribute to molecular biological research of
      mutacin. METHODS: The antibacterial activity of 80 isolated strains was tested by
      the stab culture technique against Streptococcus oralis ATCC 10557. The mutacin
      produced by strain 1G, was initially purified by solid-phase extraction (SPE)
      after crude extraction by chloroform. And then the active substances were
      purified by twice reversed-phase high performance liquid chromatography (RP
      HPLC). The purified target peptide (mutacin) was collected and freeze-dried for
      further study. RESULTS: The greatest active strain of these S. mutans isolates,
      the strain 1G was obtained. Roughly 15 microg crude mutacin was extracted from
      200 mL liquid medium of this strain 1G. The purified mutacin through SPE and
      twice RP-HPLC was obtained. CONCLUSION: It was much complex to separate and
      purify mutacin due to its small molecular mass, and extracting and purifying of
      mutacin may make an important contribution to the further research of mutacin.

PMID- 21179701
TI  - [Lipoma in deep neck: a case report].
AB  - Lipoma is one of the most common benign tumors derived from mesenchymal tissues.
      However, it is seldom to be found in deep neck. A case of lipoma in deep neck
      involving the epidural space was reported. The incidence, histopathology,
      diagnosis and treatment of this kind of disease were discussed.

PMID- 21179702
TI  - [Application of Cochrane systematic reviews in diagnosis and treatment for oral
      mucosal diseases].
AB  - OBJECTIVE: To collect evidence in diagnosis and treatment of oral mucosal
      diseases. METHODS: The Cochrane library (Issue 3, 2009) was searched to get the
      full texts of published related Cochrane systematic reviews. The results were
      summarized for recommendation to dentists. The current status of evidence based
      medicine in this field was analyzed. RESULTS: Reliable evidence for management of
      oral submucous fibrosis is still limited; amifostine, hydrolytic enzymes, ice
      chips and Chinese medicine may be effective in preventing oral mucositis for
      patients with cancer receiving radiotherapy or chemotherapy; the evidence in
      treating oral mucositis with allopurinol mouthwash, granulocyte macrophage-colony
      stimulating factor, immunoglobulin or human placentral extract for patients with
      cancer receiving treatment is weak and unreliable yet; there is evidence that
      acyclovir is efficacious in prevention and treatment of herpes simplex virus
      infections in patients being treated for cancer; there is strong evidence that
      drugs absorbed or partially absorbed from the gastrointestinal tract prevent oral
      candidiasis in patients receiving treatment for cancer; relapses and adverse
      effects are common in using beta carotene, lycopene, vitamin A or retinoids to
      treat oral leukoplakia; only some weak evidence is provided in using
      cyclosporines, retinoids, steroids or phototherapy for treating oral lichen
      planus; the evidence about acyclovir for treating primary herpetic
      gingivostomatitis is insufficient; there is little research evidence for
      treatment of burning mouth syndrome. CONCLUSION: It is essential to raise the
      quality of design and conduction of clinical trials in the field of oral mucosal
      disease to provide solid bases for systematic review, so that to improve evidence
      based treatment of these diseases.

PMID- 21179703
TI  - [Recognition of Chinese character on electrotactile vision substitution system].
AB  - In this paper, we used the eletrotactile vision substitution system designed by
      ourselves to display Chinese characters on the 16x16 electrode array through some
      simple image processing algorithms and multiplexing technology. Based on this,
      simple Chinese character recognition experiment was conducted. The result of the
      experiment shows that the electrotactile vision substitution is a feasible
      solution for the blind to read simple Chinese characters and the result also
      solidifies the foundation of further study about more complex real-time image
      electrotactile display.

PMID- 21179704
TI  - [Mobile phone based liquid crystal thermal imaging method and its medical
      implementation].
AB  - In this paper, a new medical imaging strategy based on mobile phone is developed
      to obtain the quantitative temperature mappings of human skin. The visual images
      reflected by the TLC pre-painted on human skin are captured by the camera of
      mobile phone and transformed to the thermographies of human skin through digital
      image processing method according to the Temperature-Hue curve pre-established in
      the calibration experiment. The mobile phone acquired imaging is then applied to
      reconstruct the temperature distribution of dorsal hand and for thermodynamic
      check. Additional thermal parameters related to body health status are calculated
      based on the bioheat transfer model of human body. The present method is expected
      to be developed as a pervasive and low cost way to map the skin temperature
      imaging of human body.

PMID- 21179705
TI  - [Preparation of anodic oxidation layer on the surface of pure titanium and its
      biological activity study].
AB  - This paper introduces how TiO2 film was prepared on pure titanium by anodic
      oxidation. Surface morphology and composition of the oxide film were analyzed by
      SEM coupled with EDAX. The deposition ability of hydroxyapatite of the anodized
      titanium in simulated body fluid (SBF) at 37 degrees C was evaluated. The results
      indicated that the oxide film was rough and honeycomb holes, connecting with each
      other, could be found on the surface. The holes with the diameter of 1-2 microm
      were distributed uniformly, which was typical for anodic oxidation. After
      alkaline treatment, hydroxyapatite deposition on the oxidized specimens in SBF
      was improved significantly.

PMID- 21179706
TI  - [Rapid detection device of bacteria drug-sensitivity using electrical impedance
      method].
AB  - Since the bacteria metabolites in the process of growth and reproduction of can
      lower the resistivity characteristics of the medium, the electrical impedance
      method can develop a rapid detection device of bacterial drug sensitivity. The
      device consists of micro-organisms impedance sensors, computer systems, signal
      generator, resistance Anti-detection circuit, the time allocation controller,
      constant temperature incubator and auxiliary circuits and other components. It
      measures the electrical impedance of the medium, and bacteria in the culture
      period to obtain the impedance value of the monitor into the impedance curve.
      Drug sensitivity of bacteria can be determined, using this form of differential
      impedance curve. This detection device significantly shortened the time of
      bacterial drug susceptibility testing, achieving rapid drug susceptibility
      testing of clinical medicine, drug susceptibility testing automation and
      intelligence.

PMID- 21179707
TI  - [Shearwave-based ultrasound viscoelasticity measurement system for evaluation of
      liver fibrosis].
AB  - This paper describes a liver elasticity and viscosity measurement system based on
      existing medical ultrasound platforms. This system relies on acoustic radiation
      force to invoke transient response on soft tissue, and employs displacement
      estimation algorithms to detect the propagation of shear wave. The research
      proves that the velocity of the shear wave may serve as a reliable estimation of
      the Young's modulus and viscosity coefficient of the liver tissue, and existing
      commercial products may be easily adapted to support this technique without extra
      hardware cost.

PMID- 21179708
TI  - [Assessment of parotid gland dose variations by helical tomotherapy adaptive
      system in head and neck cancer].
AB  - The paper introduces a helical tomotherapy (HT) adaptive system in assessment of
      parotid gland dose variation in head and neck cancer. The system, which helical
      therapy unit is equipped with, is based on megavoltage computed tomography (MVCT)
      images to calculate the actual volume and dose of region of interest (ROI).
      Whether to change plan is judged on the fact for the realization of adaptive
      radiotherapy. One case of nasopharyngeal carcinoma was as a sample to evaluate
      parotid gland dose variation during the treatment. On every week and last time,
      patient was scanned by MVCT before treatment, a total of eight MVCT images. As
      the treatment progressed, the parotid gland volume was shrinking and the dose was
      increasing. The parotids volume variation was negatively related with D50 and V1
      (both P < 0.05).

PMID- 21179709
TI  - [Study and design of spectral domain optical coherence tomography-based high
      resolution ophthalmic imaging system].
AB  - According to the mechanism of spectral domain optical coherence tomography, this
      paper gives a design and development of a practical OCT imaging device based on
      slit-lamp microscopic widely-used in ophthalmology. The paper details the
      device's architecture and three key points in design: communication between PC
      and MCU, how to design modules of fixation lamp and reference arm and anti
      interference measures.

PMID- 21179710
TI  - [Design of portable HGB measurement system].
AB  - This paper proposes a portable dual-wavelength HGB measurement system to avoid
      the defect that the single-wavelength HGB (Hemoglobin) admeasuring apparatus
      needs to measure the blank solution for comparison and correction, The system
      consists of constant light sources, residual, core controller based on ARM, data
      processing unit, LCD part and so on. Compared with the methods of single
      wavelength measurement, the system is proved to be high-efficiency and can work
      at a high speed, and well meet the need of clinical medicine, The technology and
      methods adopted in the system are practical and can be extensively used.

PMID- 21179711
TI  - [Development of cellular-I portable field anesthesia machine].
AB  - OBJECTIVE: To develop a portable field anesthesia machine system suitable for the
      medical first-aid on the spot. METHODS: The three-dimensional structure of PFAM
      was designed with modeling software of Pro/E and manufactured according to the
      GB9706.29 and other national standards. RESULT: Due to its small footprint and
      very light weight, PFAM is completely portable and convenient on different
      occasions within or outside a hospital environment. It can support breathing of
      patients and delivery anesthetic gas, fitted for both adult and children
      patients. All of the safety alarm systems required are employed on board.
      CONCLUSION: PFAM may play an important role in the first-aid in the field or
      outside the hospital.

PMID- 21179712
TI  - [Development on measuring method for the parameters of orthopaedic biomechanics].
AB  - This paper introduces the development on the research of measuring theory for
      orthopaedic biomechanics in detail. Then, the measuring method and corresponding
      measuring device are also mentioned. Advantages, disadvantages and development
      for the device are also introduced. Finally, the research prospect for it is
      introduced.

PMID- 21179713
TI  - [The research progress on microelectrode array (MEA) of retinal prosthesis].
AB  - This review paper presents the current research progress, challenges and future
      development on microelectrode array of retinal prosthesis, including epi-retinal
      and sub-retinal implants.

PMID- 21179715
TI  - [The electromagnetic compatibility test requirements for cardiac pacemaker in
      international standards].
AB  - Based on the latest international standards about implantable pacemakers,
      describing the main test requirements, especially for the EMC test requirements
      in details, and comparing the differences between the different standards, making
      readers having a clear understanding for the tests on pacemakers, especially for
      the EMC tests.

PMID- 21179714
TI  - [Comparison of the software safety evaluation methods in medical devices].
AB  - The article intends to analyze the software safety problems in high-risk medical
      devices based on the investigation of software R & D Quality control procedures
      in Shanghai medical device manufacturing enterprises. The idea of improving the
      software pre-market safety evaluation method in China is also explored through
      the way of comparing those in U.S. and Europe.

PMID- 21179716
TI  - [Discussion on the determination of bicarbonate in hemodialysis].
AB  - During the routine tests, it's found that the testing method related to
      Hemodialysis mentioned in the industry standard YY0598-2006 cannot reflect the
      real bicarbonate concentration in Hemodialysis. To discuss the reaction principle
      and its interference factors deeply by studying the assay determination of
      bicarbonate in Hemodialysis, and it could be cited as reference for amending the
      quality standard or troubleshooting. The improved way of determining bicarbonate
      concentration in Hemodialysis is also put up.

PMID- 21179717
TI  - [Testing of initial contamination for three kinds of surgical implants producted
      in Beijing].
AB  - The initial contamination of femoral head, femoral stem and femoral component
      producted by seven factories in Beijing is tested, all of the initial
      contamination values are 580 in total. Then these data is analyzed on statistics.
      The result indicates that the initial contamination values of three kinds of
      products according with normal distribution; The initial contamination values
      have not significant difference between femoral head and femoral component of the
      same factory; and the season has not significant effect on initial contamination
      in Beijing. According to the experimental data, the level of initial
      contamination is undulatory, so the factories should control the initial
      contamination and maintain the stability of initial contamination.

PMID- 21179718
TI  - [Comparative study of device labeling regulation in U.S.A. and China].
AB  - OBJECTIVE: To provide references for the evolvement of medical devices labeling
      and manual administration in China, METHODS: By content analysis, 10 juristic
      documents relevant to device labeling and manual were collected from FDA website,
      compared to which, the federal regulation was mainly analyzed. RESULTS: There are
      five main differences of device labeling regulation between U.S.A. and China:
      juristic system, administrative scope, administrative target, characteristics and
      practice, CONCLUSIONS: A set of comprehensive juristic system for device labeling
      has been established by FDA. from which China should draw experience, to
      administrate the prescription devices and the over-the-counter devices in
      classification, and set up device labeling guidance, thus guarantee the safety
      and efficacy of device.

PMID- 21179719
TI  - [Research on SOA for hospital information system].
AB  - Integration of heterogeneous systems in hospital is an important subject. The
      loose-coupling and efficient data interaction can be realized with SOA, the
      complexity of cross-point can be avoided with ESB and Service-Oriented when
      system integration, the unified control can come for information management.
      Finally it will meet a variety of needs related with management and business in
      hospital, adapting quickly to changes.

PMID- 21179720
TI  - [Optimization of doctor's order inputs interface and functions of electronic
      anamnesis].
AB  - The doctor's order system of electronic anamnesis is the bridge between HIS
      system and a much better service, especially when the HIS system is focused on
      its billing function. In practice, we continuously perfect and better the
      interface and functions of medical advising inputs to effectively standardize
      doctors' orders and lessen mistakes. It can also enhance working efficiency, and
      set a valid platform for medical billing management, rationalized drug use
      management, antibiotic classification management, clinical application, etc.

PMID- 21179721
TI  - [The application of operating room quality backward system in instrument place
      management].
AB  - OBJECTIVE: Improvement of the surgery instrument's clean quality, the optimized
      preparation way, reasonable arrangement in groups, raising the working
      efficiency. METHOD: We use the quality backward system into the instrument clean,
      the pack and the preparation way's question, carry on the analysis and the
      optimization, and appraise the effect after trying out 6 months. RESULTS: After
      finally the way optimized, instrument clean quality distinct enhancement; The
      flaws in the instrument clean, the pack way and the total operating time reduce;
      the contradictory between nurses and the cleans arising from the unclear
      connection reduces, the satisfaction degree of nurse and doctor to the instrument
      enhances. CONCLUSIONS: Using of operating room quality backward system in the
      management of the instrument clean, the pack and the preparation way optimized,
      may reduce flaws in the work and the waste of human resources, raise the working
      efficiency.

PMID- 21179722
TI  - [Investigation and study on pictogram commonly used in medical equipment].
AB  - Investigated and analyzed the graphical symbols commonly used in medical
      equipment, their benefits and drawbacks. From the perspective of human factors
      engineering, some root causes of poor pictogram as well as their relations with
      medical equipment adverse events were addressed. Furthermore, how to deal with
      the problems with current pictogram aiming at reducing use error was also
      discussed.

PMID- 21179723
TI  - [A thoracentesis needle with spring-loaded valve].
AB  - With the new-style thoracentesis needles with spring-loaded valve designed by
      ourselves, thoracentesis were carried out in 60 patients with ages ranging from 2
      to 74 years. The successful rate for the operation was 100% (198/198), without
      any major complications such as pneumothorax, hemothorax, pleural shock or
      infection. The results show that this kind of puncture needle is multi-purpose
      and easy to operate, with high safety and reliability.

PMID- 21179724
TI  - [Effect of Chinese drugs for benefiting-qi, activating-blood, dissolving-phlegm
      and removing-toxin combined with conventional treatment in preventing and
      treating post-operative vascular restenosis in patients with diabetic lower
      extremity arterial disease underwent percutaneous transluminal angioplasty].
AB  - OBJECTIVE: To verify the clinical efficacy of Chinese drugs for benefiting-qi,
      activating-blood, dissolving phlegm and removing-toxin (CDs) Combined with
      Conventional Treatment on post-operative vascular restenosis in patients with
      diabetic lower extremity arterial disease (DLEAD) underwent percutaneous
      transluminal angioplasty (PTA). METHODS: Fifty-six DLEAD patients underwent PTA
      of below-knee artery were assigned to the treatment group (32 patients) treated
      by basic therapy combined with CDs and the control group (24 patients) treated by
      basic therapy only. The changes in symptoms and signs, ankle/brachial index (ABI)
      and transcutaneous oxygen pressure (TCPO2) of affected limb, and blood flow (BF)
      in operated vessels checked with color Doppler examination were monitored and
      analyzed with SPSS software 16. 0. RESULTS: Overall effectiveness, including
      symptom score, ABI, TCPO2 and BF in patients after operation were all better in
      both groups significantly (P < 0.05), the improvements began to reveal in 3-6
      months, and be stabilized in the treatment group, but declined gradually in the
      control group after then. So, the effective rate in the treatment group became
      significantly higher than that in the control group (75.00% vs. 41.67%, P < 0.01)
      at the end of the 6th month, meanwhile levels of ABI (0.65 +/- 0.12), TCPO2
      (68.00 +/- 4.21 mm Hg), and BF (35.00 +/- 2.11 cm/s) in the former were better
      than those in the control group, respectively (0.44 +/- 0.12, 41.00 +/- 2.02 mm
      Hg and 21.00 +/- 1.85 cm/s, P < 0.05). CONCLUSION: CDs shows definite effect in
      post-PTA prevention of vascular restenosis in DLEAD patients.

PMID- 21179725
TI  - [Effect of Xuefu Zhuyu decoction in preventing complications of rib fracture in
      patients with blunt chest injury].
AB  - OBJECTIVE: To evaluate the clinical effect of Xuefu Zhuyu Decoction (XFZYD) on
      the incidence of complications of rib fracture in patients with blunt chest
      injury. METHODS: One hundred and twenty patients with rib fracture stratified
      according to the AIS scale in three layers (1-3) were equally assigned to two
      groups, the treated group and the control group, all received conventional
      treatment, but XFZYD was administered to patients in the treated group
      additionally. The incidence of complications in patients, including atelectasis,
      pleural effusion, pulmonary contusion, pleurocentesis and closed thoracic
      drainage, were observed. RESULTS: The incidence of pleural effusion in patients
      of AIS-1 and -2 in the treated group was 20% and 45% respectively, which was
      remarkable lower than that in the control group (55% and 85%) respectively (P <
      0.05); in the treated group, 10% patients of AIS-3, for whom close thoracic
      drainage was applied, while in the control group, the percentage reached 60%,
      showing significant difference between groups (P < 0.05). CONCLUSION: XFZYD could
      reduce the incidence of pleural effusion in patients with blunt chest injured rib
      fracture of AIS-1 or -2, and reduce the utilization of close thoracic drainage in
      those of AIS-3, so it is good for clinical practice.

PMID- 21179726
TI  - [Analysis on relationship of Chinese medicine syndrome pattern with urinary
      albumin excretion rate and its related factors in early stage diabetic
      nephropathy].
AB  - OBJECTIVE: To investigate the relationship of Chinese medicine syndrome pattern
      with urinary albumin excretion rate (UAER) and its related factors in patients
      with diabetic nephropathy (DN). METHODS: Sixty-three early stage DN patients were
      subjected to the study, the Chinese medicine syndrome patterns were
      differentiated, and their condition of methylene tetrahydrofolate reductase
      (MTHFR) C677T mutation was detected (shown by gene polymorphism of 677 base
      pairs). Meantime, plasma levels of homocysteine (Hcy), folic acid, fasting and
      postprandial glucose (FG and PG), glycohemoglobin (HbA1c), blood lipids as well
      as UAER were measured. RESULTS: Syndrome pattern was differentiated as yin
      deficiency with heat-flourishing in 17 patients, qi-yin deficiency in 24, and yin
      yang deficiency in 22; while accompanied blood stasis syndrome (BSS) was found in
      35. Gene polymorphism detection indicated that 19 patients were of CC-type, 17 of
      TT-type, and 27 of CT-type. Analysis showed that higher UAER level often revealed
      in patients with BSS, as compared with that in patients of non-BS pattern, the
      difference was statistically significant (P < 0.05). UAER levels in patients of
      different genotypes were insignificantly different (P > 0.05), but showed a
      linear regressive relation, namely positively correlated with Hcy level in
      patients of isogeneic type (r = 0.674, P < 0.05). No statistical significance was
      found between levels of UAER and other related factors (P > 0.05). CONCLUSION:
      UAER level in early stage DN patients of BSS pattern is rather higher, and it
      shows a linear regression relationship (positive correlation) with Hcy level in
      patients of isogeneic type.

PMID- 21179727
TI  - [Retrospective study on Chinese medicine syndrome patterns and their associated
      factors in patients with type 2 diabetic nephropathy stage III].
AB  - OBJECTIVE: To explore the relationship between Chinese medicine syndrome patterns
      (CMSP) and their associated factors in patients with type 2 diabetic nephropathy
      stage III (DN2-3). METHODS: Retrospective analysis was conducted on 209 patients
      with type 2 diabetes mellitus (T2DM). The patients were allocated into two
      groups, the DN2-3 group and the control group. Some related clinical materials
      and laboratory indexes, including age, course of disease, body mass index (BMI),
      glycosylated hemoglobin A1c (HbA1c), systolic blood pressure (SBP), diastolic
      blood pressure (DBP), blood levels of total cholesterol (TC), triglyceride (TG),
      high and low density lipoprotein (HDL and LDL), serum creatinine (Scr) and
      microalbuminuria (MALB) as well as their CMSP (both the essential syndrome and
      the superficial syndrome) in the DN2-3 group were collected and compared.
      RESULTS: Significant differences were found between the DN2-3 group and the
      control group in aspects of course of disease (months, 107.74 +/- 96.19 vs. 82.03
      +/- 79.10), BMI (kg/m2, 26.25 +/- 4.02 vs. 24.95 +/- 3.56) and Scr level (mmoL/L,
      71.93 +/- 24.24 vs. 65.91 +/- 13.70, P < 0.05). The qi-yin deficiency SP (38
      cases, 36.19%), and the blood stasis (51 cases, 48.58%) presented as the dominant
      essential and superficial CM-SP respectively in DN2-3 patients, holding the
      highest proportion. Analysis on the relationship of associated indices among
      patients with different CMSP showed statistical differences presented in level of
      MALB, i.e. which in pi-shen qi-deficiency SP (128.77 +/- 103.59 mg/24 h) was
      higher than in yin-deficiency dryness-fire SP and qi-yin deficiency SP (88.43 +/-
      68.93 mg/24h and 82.60 +/- 55.22 mg/24 h, P < 0.05); it also presented in HbA1c
      (%) and TG levels(mmol/L), those in stasis SP were 10.73 +/- 2.71 and 2.29 +/-
      1.58 ), in dampness SP were 8.80 +/- 2.19% and 4.37 +/- 5.92, and in stasis
      phlegm SP were 8.83 +/- 2.09 and 2.40 +/- 2.18 (all P < 0.05). CONCLUSIONS: The
      risk factors for occurrence of DN2-3 may be the course of disease, BMI and Scr.
      Qi-yin deficiency with blood-stasis is the most commonly encountered syndrome in
      patients with DN2-3. Relations of MALB with Pi-Shen qi-deficiency pattern; HbA1c
      with blood-stasis pattern, and TG with dampness syndrome are distinctly exhibited
      in them.

PMID- 21179728
TI  - [Relationship of Chinese medicine syndrome pattern with heart function and brain
      natriuretic peptide in patients with heart failure].
AB  - OBJECTIVE: To observe the relationship of Chinese medicine (CM) syndrome pattern
      with heart function detected by ultrasonic cardiography and brain natriuretic
      peptide (BNP) level in patients with heart failure (HF). METHODS: One hundred and
      sixteen inpatients of HF hospitalized in Dongfang Hospital from January, 2007 to
      January, 2009 were assigned to three groups according to their CM syndrome
      pattern differentiated, the qi-yin deficiency group (QYD), the qi-deficiency and
      blood-stasis group (QDBS) and the yang-deficiency with water overflowing group
      (YDWO). Ultrasonic cardiographic (USCG) parameters, including left ventricular
      end-systolic diameter (LVEDs), left ventricular end-diastolic diameter (LVEDd)
      and left ventricular ejection fraction (LVEF) were detected, and blood level of
      BNP was measured. RESULTS: LVEF was decreased while BNP was increased in patients
      with syndrome patterns in the order of QYD --> QDBS --> YDWO, and showed
      significant difference between groups (P < 0.01); CM syndrome patterns was
      related with all the USCG parameters and BNP level, especially the BNP (r = 0.71,
      P < 0.05) and LVEF (r = -0.34, P < 0.05). CONCLUSION: LVEF and BNP can reflect
      the severity of heart failure, and they could be taken as the beneficial
      objective and quantitative indices for syndrome pattern differentiation.

PMID- 21179729
TI  - [Influence of Shengxue mixture on the expression of T-bet/GATA-3, their relevant
      signal transduction molecules, cytokines, and Th1/Th2 balance in patients with
      chronic aplastic anemia].
AB  - OBJECTIVE: To study the actions of transcription factors, T-bet and GATA-3, and
      their relevant signal transduction pathways on the immune-related pathogenesis
      with chronic aplastic anemia (CAA), and to investigate the immunological
      regulation mechanism of Shengxue Mixture (SXM) in regulating levels of Th cell
      imbalance, transcriptional factor and relevant signal pathways. METHODS: All CAA
      patients selected from Yueyang Hospital of Shanghai University of traditional
      Chinese medicine were equally randomized into the treated group and the control
      group, 20 patients in each group, and 20 healthy persons were selected as normal
      group, the former was treated with SXM according to patients' syndrome patterns,
      namely, SXM-1 was given to patients of Pi-Shen yang-deficiency pattern, and SXM-2
      to those of Pi-Shen yin-deficiency pattern. Patients in the control group were
      treated with cyclosporin A (CsA). The mRNA expressions of T-bet, GATA-3, signal
      transducers and activators of transcription 4 (STAT4) and 6 (STAT6) in peripheral
      blood mononuclear cell (PBMNC) of patients were determined using real-time
      fluorescent quantitation polymerase chain reaction before and after treatment,
      meantime, the Th1/Th2 proportion in peripheral blood, and levels of IFN-gamma, IL
      12 and IL-4 in PBMNC-cultured supernatant were detected by flow cytometry and
      enzyme linked immunosorbent assay. RESULTS: The mRNA expressions of PBMNC T-bet
      and STAT4, ratios of T-bet/GATA-3, Th1 proportion and Th1/Th2 ratio, levels of
      IFN-gamma and IL-12 in PBMNC-cultured supernatant were all significantly higher
      in CAA patients than in healthy controls (P < 0.01), which were lowered after
      treatment but didn't reach the normal range (all P < 0.01), excepting for IL-12
      level. Comparisons of the changes between the two treated groups showed
      insignificant difference (P > 0.05). While the difference between patients and
      healthy persons in terms of GATA-3, STAT6, Th2 proportion, and IL-4 were
      insignificant (P > 0.05), either before or after treatment. CONCLUSIONS: Abnormal
      activation of IFN-gamma/T-bet and IL-12/ STAT4 pathways, as well as Th1/Th2
      balance deviating to Th1 excursion play vital roles in the immunological
      pathogenesis of CAA. SXM and CsA could lower the aforesaid abnormal activation
      and correct Th1 hyper-polarization, so as to alleviate the over-activated cell
      mediated immunity to eliminate hematopoietic depression in CAA patients.

PMID- 21179730
TI  - [Comparative research and follow-up study on treatment of spastic cerebral palsy
      with Jiaji (EX-B2) point needling].
AB  - OBJECTIVE: To observe the clinical effects of Jiaji (EX-B2) needling for
      treatment of spastic cerebral palsy (SCP). METHODS: Sixty-two SCP patients were
      randomized into two groups, the treatment group treated by needling, and the
      control group treated by sham-acupuncture, once every day for 60 times totally.
      The clinical effect was assessed with scoring by the modified Ashworth's scale
      (MAS), gross motor function measuring scale (GMFM) and WeeFIM at the end of
      treatment (T1), half-year (T2) and 1-year (T3) after treatment. RESULTS: Clinical
      effectiveness assessment showed that MAS scores in the treatment group reduced
      significantly and steadily at all the time points (P < 0.01), while in the
      control group, it reduced significantly at T1 (P < 0.01), but raised again at T2
      and T3 to higher than that in the treatment group (P < 0.05, P < 0.01),
      approaching the baseline level (P > 0.05). GMFM and WeeFIM scores increased in
      both groups at all the three assessing time points (P < 0.01), but the increments
      in the treatment group were higher than those in the control group respectively
      (P < 0.01, P < 0.05). CONCLUSION: Jiaji (EX-B2) needling could achieve good
      clinical therapeutic effects on SCP.

PMID- 21179731
TI  - [Application and effect of auricular acupoint pressing for analgesia in
      perioperative period of total knee joint replacement].
AB  - OBJECTIVE: To observe the effect of auricular acupoint pressing (AAP) for
      analgesia during perioperative period of total knee joint replacement. METHODS:
      Sixty patients with osteoarthritis of ASA grade I - III scheduled to receive
      unilateral total knee joint replacement were equally randomized into the AAP
      group and the control group, 30 in each group. The general anesthesia on all
      patients was implemented by physicians of an identical group through endotracheal
      intubation. To the patients in the AAP group, AAP with Vaccaria seed was applied
      before operation, and the local analgesia on affected limb with acupoint pasting
      was used after operation. Besides, administering of celecoxib 400 mg on the day
      before operation, and celecoxib 200 mg twice daily post-operation was given to
      all patients. When the visual analogue scales (VAS) reached more than 7 points,
      0.1 g of bucinnazine hydrochloride was given for supplement. Meantime, same post
      operative training methods were adopted in both groups. The resting VAS pain
      scores, contentment of sedation, incidence of adverse event, postoperative range
      of motion (ROM) of knee joint and Hospital for Special Surgery (HSS) score were
      recorded. RESULTS: The resting VAS pain scores at 6 h and 24 h after operation
      was 5.99 +/- 0.67 scores and 4.26 +/- 0.59 scores in the AAP group respectively,
      which was significantly lower than that in the control group at the corresponding
      time (7.02 +/- 0.85 scores and 4.92 +/- 0.43 scores, P < 0.01); but it showed
      insignificant difference between the two groups at 1 h and 48 h after operation
      (P > 0.05); sedation contentment in the two groups was similar; incidence of
      adverse event in the AAP groups seemed lower (4 cases vs. 11 cases), but the
      intergroup difference was statistically insignificant (P > 0.05). ROM before
      surgery were 75.63 degrees +/- 5.74 degrees and 75.43 degrees +/- 5.63 degrees in
      the two groups respectively, showing no significant difference (P > 0.05), two
      weeks after operation, the initiative ROM raised to 96.50 degrees +/- 3.79
      degrees and 93.50 degrees +/- 3.50 degrees, and the passive ROM reached 107.8
      degrees +/- 3.37 degrees and 105.27 degrees +/- 3.25 degrees in the two groups
      respectively, with statistical significance between them (P < 0.05). HSS score
      was similar between groups before operation (60.23 +/- 3.44 scores vs. 61.70 +/-
      2.83 scores, P > 0.05); while it became 86.97 +/- 2.33 scores and 85.37 +/- 2.30
      scores after operation, showing significant difference between groups (P < 0.05).
      CONCLUSION: Applying auricular acupoint pressing in perioperative period of knee
      joint replacement is favorable for alleviating postoperative pain, decreasing
      narcotic consumption, and promoting early rehabilitation, and it has the
      advantages of low cost, less complication, simple manipulation and high safety.

PMID- 21179732
TI  - [Effects of mild warming moxibustion on acupoints Shenque (RN8) and Guanyuan
      (RN4) for prevention and treatment of recurrent respiratory tract infection in
      children with cerebral palsy].
AB  - OBJECTIVE: To investigate the clinical effect of mild warming moxibustion (MWM)
      on acupoints Shenque (RN8) and Guanyuan (RN4) for treatment of recurrent
      respiratory tract infection (RRTI) in children with cerebral palsy (CP). METHODS:
      Sixty-four CP patients with RRTI were randomly and equally assigned to two
      groups, all received conventional rehabilitation treatment, but in acute
      infection stage, MWM was applied on the treated group, and intravenous dripping
      of immunoglobulin was given to the control group, all for 3 months. The frequency
      of RRTI attacking (Fre), the mean cough alleviating time (T-CA) and rale
      disappearing time (T-RA) during infection, as well as the serum levels of immune
      globulins during the post-treatment 1-year follow-up period were observed.
      RESULTS: The effectiveness in the treated group was better than that in the
      control group, showing in aspects of Fre (2.38 +/- 0.64 times vs. 6.50 +/- 0.84
      times), T-CA (3.92 +/- 1.32 days vs. 6.48 +/- 2.18 days) and T-RA (4.66 +/- 1.82
      days vs. 7.64 +/- 1.44 days), significant difference was shown between groups (P
      < 0.01). The serum levels of IgG, IgM and IgA all raised in both two groups (P <
      0.05), comparison of immunoglobulin levels between groups showed that they were
      lower immediately after treatment, but higher at the end of the 1-year follow-up
      in the treated group than those in the control group. CONCLUSION: MWM on
      acupoints Shengue and Guanyuan has a better and long-term clinical effect for
      treatment of RRTI in children with CP.

PMID- 21179733
TI  - [Effect of Tangzhiping granule on blood lipids and free fatty acids in rats with
      insulin resistant diabetes].
AB  - OBJECTIVE: To investigate the effects of Tangzhiping Granule (TZPG) on blood
      lipids and free fatty acids (FFA) in rats with insulin resistant diabetes (IRD).
      METHODS: A blank control group consisted of randomly selected normal rats was set
      up. The remaining rats were established to IRD model by high-fat high-sugar diet
      feeding and streptozotocin injection. Then the 32 successfully modeled rats were
      randomized into the model group (treated by saline), the Tangmaikang group
      (treated with Tangmaikang Granule 1.35 g/kg), and the two TZPG groups treated
      with high dose (2.70 g/kg) and low dose TZPG (1.35 g/kg) respectively through
      intragastric infusion for 4 weeks. The body weight (BW), fasting blood glucose
      (FBG), insulin (INS), blood lipids including triglyceride (TG), total cholesterol
      (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein
      cholesterol (HDL-C), and FFA were detected, and the insulin sensitivity index
      (ISI) calculated. RESULTS: Compared with the blank control group, BW, FBG and INS
      increased while ISI decreased in the model group (P < 0.05 or P < 0.01). All the
      above-mentioned abnormal indices were improved in the three treated groups
      (Tangmaikang, high and low dose TZPG group), but the improvements in the high
      dose TZPG group were more significant than those in the other two groups (P <
      0.05 or P < 0.01). Similar outcomes were also seen in blood lipids detection, in
      which TG, TC, LDL-C and FFA were higher and HDL-C were lower in model rats than
      those in blank controls, they were improved in the three treated groups (P <
      0.05), and the best improvements were seen in the high dose TZPG group (P <
      0.05). CONCLUSION: TZPG could reduce levels of BW, FBG, INS, TC, TG, LDL-C and
      FFA, and increase levels of ISI and HDL-C in rat model of insulin resistant type
      2 diabetes, so as to improve the insulin resistance in them.

PMID- 21179734
TI  - [Effect of Qingyi Huaji formula for inhibition of pancreatic cancer cell growth
      through down-regulating Ski expression].
AB  - OBJECTIVE: To explore the action mechanism of action of Qingyi Huaji Formula
      (QYHJ), whether its inhibition on the growth of the tumor is by way of down
      regulating Ski expression. METHODS: SW1990 tumor cell with low Ski expression was
      created by lenti-virus mediated RNA interfering technique. Tumor cells with
      different levels of Ski expression were subcutaneously transplanted to nude mice,
      and the response of cancer cells to QYHJ treatment was detected. RESULTS: After
      QYHJ treatment, the tumor growth slowed-down significantly, with the Ski mRNA and
      protein expressions in tumor reduced by 39.6% and 41.3% of that in untreated
      tumor respectively (P < 0.05). Ski mRNA and protein expressions in the created
      high and low Ski expression tumor cells were 105%, 123% and 46%, 30% respectively
      of that in parental cells (P < 0.05). The tumor weight inhibitory rates of QYHJ
      on high Ski expression cells were 29.6% and 32.2%, while on low Ski expression
      cells, it was 16.0% to 17.8% (P < 0.05). CONCLUSION: Ski acts as an important
      therapeutic target of QYHJ in treating SW1990 pancreatic cancer, and its
      expression status mediates different response of tumor cells to QYHJ treatment.

PMID- 21179735
TI  - [Experimental study on extracts from ginseng, notoginseng and chuanxiong for
      delaying vascular aging in senescent mice].
AB  - OBJECTIVE: To explore the vascular structural and functional change in aged mice,
      and the intervention roles of extracts from ginseng, notoginseng and chuanxiong
      (Exs) on it. METHODS: The mice model of natural aging was built, and all model
      mice were divided into 5 groups, the model group, the Vitamin E group treated
      with vitamin E, and the three Exs groups treated with high, middle and low dose
      Exs respectively. Besides, a normal control group was set up with young rats.
      Morphological change of aorta was observed by HE and Masson staining, levels of
      plasma angiotensin-II (Ang II), anti-superoxide anion, advanced glycation end
      products (AGEs), matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of
      metalloproteinase 2 (TIMP-2) in vascular tissue, as well as the MMP-2/TIMP-2 were
      detected. RESULTS: Aged aortic morphologic change in model rats was ameliorated
      in the Exs treated groups, decreased vascular endothelial exfoliative cells and
      vascular smooth muscle cell (5MG) proliferation were shown in HE staining. Masson
      staining analysis showed relative content of collagen fibers reduced in all Exs
      treated groups (P < 0.05) and that of SMC decreased in high-dose Exs group (P <
      0.05). Moreover, levels of vascular tissue anti-superoxide anion, TIMP-2 and MMP
      2/TIM-2 ratio were obviously higher, AGEs and MMP-2 were significantly lower in
      all Exs treated groups than those in the model group respectively, showing
      statistical significance (P < 0.05). CONCLUSION: Exs can ameliorate the aged
      changes in aortic morphology, reduce the production of reactive oxygen species
      (ROS) and AGEs in vascular tissue, inhibit MMP-2 activity and regulate MMP-2/TIMP
      2 equilibrium, so it reduces the vascular stiffness degree of senescent mice,
      decreases vascular remodeling and delays the occurrence of vascular aging
      ultimately.

PMID- 21179736
TI  - [Effects of Shenshuai Yangzhen capsule on hypothalamic leptin-neuropeptide and
      proopiomelanocortin axes in chronic renal failure rats with malnutrition].
AB  - OBJECTIVE: To investigate the effect of Shenshuai Yangzhen Capsule (SYC) on
      hypothalamic leptin-neuropeptide Y (NPY) and proopiomelanocortin (POMC) axes in
      chronic renal failure (CRF) rats with malnutrition (MN). METHODS: Forty-two male
      SD rats of SPF grade were established into CRF-MN model by 5/6 nephrectomy and 4%
      casein diet, the happening time of MN in them was recorded. Rats successfully
      modeled were randomized into three groups, 11 rats in Group A treated with SYC,
      11 in group B treated with composite alpha-keto acid and 12 in Group C was
      untreated. Besides, a normal control group was set up with 8 healthy rats. After
      being treated for 4 weeks, the renal function related indices, including serum
      creatinine (Scr), blood urea nitrogen (BUN), 24 hour urine protein (24 h Upro),
      albumin (ALB), haemoglobin (Hb) insulin like growth factor-1 (IGF-1), total
      cholesterol (TC) and triglyeride (TG) were measured, and body weight, food intake
      in rats were observed dynamically, blood leptin and NPY level in rats were
      determined by radioimmunoassay; mRNA expressions of OB-Rb, NPY and POMC in
      hypothalamus were detected with RT-PCR. RESULTS: CRF rats revealed MN at the end
      of 10th week after modeling. Compared with Group C, the condition of MN in Group
      A was significantly improved, showing increase of food intake and body weight (P
      < 0.05), marked improvement of renal function (P < 0.05), decrease of LP and NPY
      levels in plasma (P < 0.05), as well as up-regulated NPY mRNA expression and down
      regulated mRNA expressions of OB-Rb and POMC in hypothalamus (P < 0.01).
      CONCLUSION: SYC can improve the malnutrition condition in rats with CRF, which is
      possibly by way of depressing OB-Rb and POMC mRNA expression and upgrading NPY
      mRNA expression in hypothalamus.

PMID- 21179737
TI  - [Protective effects of Paecilomyces hepiali Cs-4 on rats with adriamycin-induced
      nephropathy].
AB  - OBJECTIVE: To study the renal protective effect of Paecilomyces hepiali Cs-4
      (Abbr. to Cs-4) on rats with adriamycin-induced nephropathy (AIN). METHODS:
      Twenty-four male SD rats were randomly divided into four groups: the control
      group (A), the model group (B), the Benazepril group (C), and the Cs-4 group (D).
      AIN rat model was established by left unilateral nephrectomy and repeated caudal
      vein injection of adriamycin. Gastric perfusion of Cs-4 [500 mg/( kg x d)] and
      Benazepril [4 mg/( kg x d)] was given respectively to the groups D and C,
      starting from 1 week after modeling. Blood biochemical indices including blood
      urea nitrogen (BUN), serum creatine (Scr) and 24-hour urinary protein excretion
      (24 h-UP) were assessed 4 and 8 weeks after medication. Rats were sacrificed at
      the end of 8-week medication, their renal tissue was get for pathological
      examination with electric microscopy, the expressions of fibronection (FN),
      collagen IV (COL-IV ) and osteopont (OPN) in renal tissue were assessed by
      immunohistochemistry. RESULTS: Levels of 24h-UP, BUN, Scr, mesengial matrix
      percentage, as well OPN, FN, COL-IV were significantly lower in group D than in
      group B (P < 0.05); and the fat metabolic disorder was improved in group D (P <
      0.05). CONCLUSION: Cs-4 displays its renal protective action in rats with AIN
      through reducing the urinary protein excretion, correcting lipid metabolic
      disturbance, inhibiting the over accumulation of extracellular matrix, improving
      the pathological damage of kidney, thus restoring the renal function.

PMID- 21179738
TI  - [Effect of muscovite on non-steroidal anti-inflammatory drug associated
      intestinal injury and its influences on tumor necrosis factor-alpha and nuclear
      factor-kappaB in rats].
AB  - OBJECTIVE: To examine the efficacy of muscovite on non-steroidal anti
      inflammatory drug (NSAID) associated intestinal injury in rats, and its
      influences on the expressions of inflammatory factors, tumor necrosis factor
      alpha (TNF-alpha) and nuclear factor-kappaB (NF-kappaB), for researching its
      possible mechanism of intestinal mucosal protection. METHODS: NSAID associated
      intestinal injury in rat was induced by intra-gastric infusion of diclofenac.
      Twenty-four male Sprague-Dawley rats were randomly and equally assigned to three
      groups: normal control group, model control group and Muscovite group, 8 in each
      group. The normal control group received physiological saline 1 mL/100 g and the
      other two groups received diclofenac 7.8 mg/kg respectively every day for 5 days;
      while to the Muscovite group, Muscovite 120 mg/kg was gastric infused once on the
      day before modeling, followed with 120 mg/kg per day, given an hour before
      diclofenac infusion in the modeling days. All rats were killed on the 6th day,
      their gross changes and histological injury of intestinal mucosa were observed
      and scored, serum level of TNF-alpha was assayed in radioimmunoassay and NF
      kappaB activity was determined by immunohistochemistry. RESULTS: The small dosage
      diclofenac administration can cause intestinal damage, revealing obviously
      erythema, erosion, multiple ulcer, intestinal stricture, even perforation, etc.
      Intestinal injury in the Muscovite group was obviously milder than that in the
      model control group, only showed changes of local congestion, edema and erosion.
      The scores of gross and histological intestinal features in the model control
      group were 4.38 +/- 1.41 and 4.00 +/- 1.85, while in the Muscovite group were
      1.25 +/- 1.58 and 1.75 +/- 0.71, respectively, all higher than those in the
      normal control group (0.00 +/- 0.00 and 0.00 +/- 0.00, P < 0.01 and P < 0.05),
      respectively, but the elevation in the model control group were more significant
      (P < 0.05). Similar results were shown in comparisons of TNF-alpha and NF-kappaB
      levels between groups, the values were 6.19 +/- 2.76 and 1.38 +/- 1.19 in normal
      control; 22.20 +/- 5.42 and 5.75 +/- 0.46 in model control; 9.61 +/- 4.02 and
      0.13 +/- 0.35 in the Muscovite group, respectively (all P < 0.01). CONCLUSION:
      Muscovite could effectively reduce the NSAID associated intestinal mucosal injury
      by inhibiting the activity of NF-kappaB in intestinal mucosa, and down-regulating
      the expression of TNF-alpha in blood plasma, so muscovite is proved to have
      protective function for intestine.

PMID- 21179739
TI  - [Effects of Jiangu granule containing serum on the cyclins in rat's osteoblast at
      G1 phase].
AB  - OBJECTIVE: To investigate the effects of Jiangu granule containing serum (JGG
      serum) on the cyclins in rat's osteoblast at G1 phase. METHODS: Osteoblasts
      isolated by enzymatic digestion from SD rats were cultured and intervened with
      JGG-serum or normal saline (as control) respectively. Cell generation cycle was
      detected by flow cytometry, and expressions of Cyclin D1, cyclin-dependent kinase
      4 (CDK4), oncogene protein (P21) in the osteoblast were detected dynamically
      using immuno-cytochemical and RT-PCR technique. RESULTS: As compared with the
      control, the cell generation cycle and cell proliferation were proceeding quicker
      in the JGG-serum (20%) intervention group; with higher protein and mRNA
      expressions of Cyclin D1 and CDK4, as well as much lowered expressions of P21 in
      nuclei of osteoblast detected at all time points (24 h, 48 h and 72 h after
      treatment, P < 0.05 or P < 0.01). CONCLUSION: JGG-serum can adjust the G1 phase
      cyclins in osteoblast cultured in vitro, increase the mRNA and protein
      expressions of Cyclin D1 and CDK4, and inhibit P21 expression, so as to
      accelerate the proliferation of osteoblast.

PMID- 21179740
TI  - [Dynamic physiologic and pathologic changes in brain of rat with middle cerebral
      artery obstruction and effects of acupuncture in different frequencies on them].
AB  - OBJECTIVE: To study the dynamic changes of capillaries and inflammatory cells in
      different regions of brain in rat with middle cerebral artery obstruction (MCAO),
      and the effects of acupuncture in different frequencies on them. METHODS: In
      reference to Zea-Longa's method, rat model of MCAO was established by thread
      ligation. Shuigou point (DU26), the main acupoint for "awakening brain and
      opening apertures", was stimulated by high (180 times/s) or low (60 times/s)
      frequency puncturing 5 s every 12 h for 6 times totally. The amount of
      capillaries (AC) and inflammatory cells (AIC) in brain cortex (BC), hippocampus
      (Hp) and corpus striatum (CS) was counted. RESULTS: Changes in AC and AIC of all
      brain regions (except for CS) in rats immediately after modeling were
      statistically insignificant (P > 0.05). But 72 h later, AC in CS decreased, AC in
      Hp, AIC in BC and AIC in Hp increased significantly in the modeled rats, showing
      significant difference to the normal level, but AIC reduced to approach the
      normal. As compared with the rats un-intervened, AIC in BC and Hp was decreased
      in rats intervened with high frequency puncturing, AC and AIC in CS were
      increased in rats intervened by slow frequency puncturing (both P < 0.05).
      CONCLUSION: Amount of capillaries and inflammation cells are changed dynamically
      in MCAO rats after brain ischemia, showing evident brain regional specificity;
      the ischemic improving effects of acupuncture in different frequencies are
      various in their action rings, also showing brain regional specificity.

PMID- 21179741
TI  - [Evaluation of blood-stasis pattern related information in myocardial ischemic
      rat model].
AB  - OBJECTIVE: To investigate the syndrome property of myocardial ischemic (MI) model
      rats, and to objectively evaluate the blood stasis pattern related information in
      them. METHODS: SD rats were established to MI model by left anterior descending
      coronary artery (LAD) ligation. Global physical signs observation, colorimetric
      analysis on images of auricle, plantar and tongue, as well as the hemorrheologic
      indices detection were conducted dynamically at various time points after
      modeling. LARS regression was subjected to calculate the correlation between the
      color and hemorrheologic indices. RESULTS: Both colorimetric and hemorrheologic
      indices in MI rats were significantly different to those in sham-operated rats
      (control) on day 7-28 after operation, showing significant difference between
      them in terms of plantar R on day 7 (176.29 +/- 4.96 vs. 182.04 +/- 6.35, P <
      0.05); R, G and B values of plantar on day 14, 21 and 28; G and R values of
      tongue on day 14 and G value of auricle on day 21 (130.38 +/- 7.52 vs. 138.02 +/-
      9.32, P < 0.05), as well as B value of tongue on day 28 (93.70 +/- 4.79 vs. 85.80
      +/- 6.60, P < 0.01). Results of hemorrheologic indices showed that hematocrit in
      MI rats was higher than that in control on day 14 and 28 (P < 0.05), it was even
      higher on day 21 (45.38 +/- 1.96 vs. 41.50 +/- 2.12, P < 0.01); and platelet
      aggregation rate (PAR) was significantly higher in MI on day 7 (49.35 +/- 6.74
      vs. 37.83 +/- 9.94, P < 0.01) and day 14 (58.19 +/- 7.57 vs. 48.00 +/- 10.44, P <
      0.05). Besides, various degree of changes could also be seen in whole blood
      apparent viscosity and reduced viscosity at different shear rate on day 7-28 in
      the model group. LARS regression showed there existed correlation of local
      colorimetric indices with levels of hematocrit and PAR. CONCLUSION: MI model rat
      induced by LAD ligation can be diagnosed as the qi-deficiency and blood stasis
      syndrome, indications of the syndromes could be seen on 7-28 days after
      operation; the change of colorimetric indices of local images in MI rats might be
      related with their levels of hematocrit and PAR.

PMID- 21179742
TI  - [Effect of Pingtang recipe containing drug-serum on INS-1 pancreatic beta cells
      lipoapoptosis].
AB  - OBJECTIVE: To observe the effect and mechanism of Pingtang Recipe containing drug
      serum (DS-PTR) in improving INS-1 beta pancreatic cells lipoapoptosis. METHODS:
      Experimental INS-1 beta cells were divided into 5 groups (6 pools for each
      group), namely, the blank control group treated with rat's serum (C), the other 4
      model groups induced into lipoapoptosis by palmitic acid and treated respectively
      by rat's serum (M), high, middle and low dose DS-PTR (DSh, DSm and DSI). Cell
      apoptosis was detected by TUNEL staining; Caspase-3 activity of cells was
      measured by chemiluminescence method; intracellular production of reactive oxygen
      species (ROS) was detected by DCHF-DA incorporation, and expressions of
      uncoupling protein-2 (UCP-2) was determined by RT-PCR. RESULTS: INS-1 beta cell
      apoptosis in Group M was significantly higher than that in Group C (P < 0.01),
      while that showed a decreased trend in the three DS-PTR treated groups. Caspase-3
      activity was enhanced in Group M, it decreased significantly in Group DSm (P <
      0.05). The over-produced ROS in cells after modeling was inhibited in Groups DSm
      and DSI (P < 0.05), meantime, expression of UCP-2 excited by PA (2.244 +/- 0.421)
      was reduced significantly in Group DSI and Group DSm to 1.286 +/- 0.373 (P <
      0.01) and 1.627 +/- 0.348 (P < 0.05) respectively. CONCLUSION: DS-PTR shows a
      protective effect on INS-1 beta pancrentic cells against lipoapoptosis, which is
      possibly play its mechanism through regulating ROS and UCP-2.

PMID- 21179744
TI  - [Medical data mining on cases of diabetic peripheral neuropathy from professor
      Wei Zi-Xiao].

PMID- 21179743
TI  - [Phenotype change of airway smooth muscle cell in bronchial asthma rats and the
      intervention of Zhichuan capsule on it].
AB  - OBJECTIVE: To investigate the phenotype change of airway smooth muscle cell (SMC)
      in bronchial asthma and the effect of Zhichuan Capsule (ZCC) on it. METHODS:
      Sixty male SD rats were randomized into 5 groups equally, the normal control
      group, the model group, and three treated groups treated with ZCC, Western
      medicine (WM) and ZCC + WM respectively. Excepting rats in the control group,
      they were all made into bronchial asthma model rats and received respective
      treatment. Histomorphology of the airway SMC was observed by electron microsope
      at the 4th week, and the expressions of smalpha-actin and sm-MHC were examined at
      the 2nd and the 4th week after provocation. RESULTS: As compared with the control
      group, moyfilaments in SMC were lesser, secretive organelles were more and levels
      of smalpha-actin and sm-MHC expressions at the 4th week were lower in the model
      group (P < 0.05). While histomorphology of SMC in the WM group was as narmal, but
      some hypoxia changes were seen, such as the fracture of mitochondria cristae and
      deplation of matrix; histomorphology of SMC in the ZCC treated group and the ZCC
      + WM treated group were similar to that in the normal control group, and their
      expressions of smalpha-actin and sm-MHC were enhanced as compared to those in the
      model group (P < 0.05). CONCLUSION: Airway SMC changes from contractile phenotype
      to synthetic phenotype in asthma rats, but the progress of change may be
      inhibited by ZCC.

PMID- 21179745
TI  - [Indirect and direct effects of absorption components of composite for activating
      blood and removing stasis on coronary microvascular dysfunction and myocardial
      cell apoptosis].
AB  - It has been found that in case of targeted for coronary microvascular dysfunction
      and myocardial cell apoptosis, the anti-apoptosis effect of Guanxin No. 2, a
      Chinese herbal composite for activating blood and removing stasis (ABRS), is
      identical to that of its three absorption components (ferulic acid, Danshensu and
      hydroxylcarthamin yellow), and there exists a dose/myocardial flow-dependent
      direct or indirect acting path. Based on which, a hypothesis regarding the
      dose/myocardial flow related direct/indirect action of Chinese ABRS composite,
      with the same targets as before, was put forward by the authors in this paper,
      that is, the myocardial protective effect of acute high dose administration of
      the composite is acted through indirectly path by increasing the myocardial flow
      (MF); while that of chronic low dose administration is realized directly without
      change of MF. The evidence and significance of this hypothesis were discussed.

PMID- 21179746
TI  - [Deliberation on some titles in the textbook of Science of Exogenous Febrile
      Diseases].

PMID- 21179747
TI  - [Progress in study of prevention and treatment of podocyte injury with Chinese
      medicine and its effective composition].

PMID- 21179748
TI  - [Progress in prevention and treatment of liver precancerous lesions].

PMID- 21179749
TI  - [Effects of sinomenine on intracellular free calcium concentration and the
      activity of protein kinase in cultured rabbit aortic smooth muscle cells].
AB  - AIM: To explore the effects of sinomenine(Sin) on intracellular free calcium
      ([Ca2+]i) and the activity of PKC (protein kinase C) of the cultured aortic
      vascular smooth muscle cells (VSMC) during ischemia and hypoxia. METHODS: The
      effect of Sin on changes in [Ca2+]i were determined in cultured rabbit VSMC after
      exposure to high K+, norepinephrine (NE) and caffeine (Caf). Fluorescent Ca2+ 
      indicater fura-2/AM was used. The effects of Sin were compared with that of
      verapamil (Ver). The hypoxia model was made, then the activity of PKC was
      measured by y scintillation counting instrument. RESULTS: Sin (10 x 10(-6) mol x
      L(-1), 3 x 10(-5) mol x L(-1) 10(-4) mol x L(-1)) inhibited the elevation of
      [Ca2+]i induced by high K+ -depolarization in a concentration dependent manner.
      In addition, Sin inhibited the elevation of [Ca2+]i induced by NE in the presence
      of extracellular Ca2+. In the absence of extracellular Ca2+, Sin (3 x 10(-5)
      mol.L(-1)) also had no blocking effect on the NE-induced [Ca2+]i increase. It was
      found that the activity of PKC treated with Sin in VSMC cytoplasm and cell
      membrane in normal condition increased, the activity of PKC in cytoplasm in
      ischemia and hypoxia situation increased, but the activity of PKC in cell
      membrane decreased. When VSMC was treated with Sin, the activity of PKC in
      cytoplasm decreased and that of cell membrane increased. CONCLUSION: The results
      suggest that Sin might decrease the[Ca2+] i of VSMC by blocking both VDC and ROC,
      could regulate the PKC activities induced by ischemia and hypoxia.

PMID- 21179750
TI  - [Study on effects of pUDKH administration locally on physiological and
      biochemical changes in dogs with limb ischemia].

PMID- 21179751
TI  - [Effect of ligustrazine and L-arginine on function of mitochondria in myocardium
      after ischemia/reperfusion injury of myocardium in rabbits].
AB  - AIM: To study the effect of ligustrazine (LGT) and L-arginine(L-Arg)on function
      of mitochondria in myocardium after myocardial ischemia/reperfusion injury
      (MI/RI). METHODS: 50 rabbits were randomly divided into five groups (n=10):
      Control group(A), MI/R group(B), MI/R + LGT group (C), MI/R+ L-Arg group (D),
      MI/R+ LGT + L-Arg group (E). The mitochondrial respiratory function, Ca2+
      concentration ([Ca2+]m), malondialdehyde (MDA) content and superoxide dismutase
      (SOD) activity were deter mined. Meanwhile, the contents of ATP and EC in the
      myocardial tissue were measured, respectively. RESULTS: It was found that
      mitochondrial respiratory control rate (RCR), state 3 (ST3), SOD in C, D, E group
      were higher than those of B group, state 4 (ST4), [Ca2+]m, MDA were lower than
      those of B group, ATP and EC levels of myocardial tissue were higher than those
      in B group; and there were not significant differences between E and A group of
      above. CONCLUSION: LGT and IL-Arg can improve function of mitochondria in
      myocardium after ischemia/reperfusion injury of myocardium in rabbits by
      decreasing oxygen free radical level and Ca" overload in the mitochondria.

PMID- 21179752
TI  - [Effect of EGb and quercetin on culture neonatal rat cardiomyocytes hypertrophy
      and mechanism].
AB  - AIM: To investigate the effect of extract of ginkgo biloba (EGb) and quercetin
      (Que) on the hypertrophic response induced by angiotensin II (Ang II) in the
      primary culture of neonatal rat cardiomyocytes and its mechanism. METHODS: Total
      protein content of cardiomyocytes was measured by lowry's method. Superoxide
      dismutase (SOD) activity and malondialdehyde (MDA) content were measured by SOD
      and MDA assay kits. The expression of phospho-ERK1/2, phospho-JNK and phospho-P38
      were detected by Western blot. The expression of c-fos mRNA was checked by RT
      PCR. RESULTS: (1) The total protein content and cell size of cardiomyocytes
      increased significantly after Ang II treatment, EGb and Oue inhibited these
      effects of Ang II. (2) EGb and Que were able to enhance the SOD activity and
      reduce the production of MDA. (3) Ang II significantly activated ERK1/2, JNK and
      P38, only JNK activation was inhibited by Que and DPI but not ERK1/2 and P38
      activation. (4) EGb, Que, Captopril and DPI all decreased Ang II-stimulated early
      response gent c-fos mnRNA expression. CONCLUSION: EGb and Que could inhibit AngII
      induced cardiomyocyte hypertrophy through a ROS-dependent pathway, the effect of
      Que might be related to the JNK and c-fos cascade.

PMID- 21179753
TI  - [The protective effect of polysaccharide extracted from Laminaria japonica Aresch
      on vessels endothelial cell injury inducing by adrenaline].
AB  - AIM: To study the protective effect of Polysaccharide of Laminaria L01 on
      endothelial cell injury inducing by adrenaline. METHODS: In order to observe the
      influence of L01 on the release of vWF in endothelial injured rats and HUVEC
      stimulated by adrenaline, a rat model of endothelial injury was established via
      injecting adrenaline, the damaged degree of vascular endothelial was evaluated by
      aortic immunity histochemistry, HUVEC was cultured in vitro, the content of vWF
      in rat plasma and in supernatant was measured by ELISA. RESULTS: The measure of
      intact endodermis lengths (microm) stained by immunohistochemistry demonstrated
      the length in L01 high-dose group and low-dose group was obviously longer than
      that of model group (P < 0.05) in the 4th and 5th day during the model made. The
      content of vWF in rat plasma of L01 high-dose group was lower than that of model
      group (P < 0.05) in the 4th day, there were significant differences between this
      two groups, and the content of vWF in rat plasma of both L01 high-dose group and
      low-dose group was lower than that of model group (P < 0.05) in the 4th and 5th
      days. In the study of cultured HUVEC, on the 24 h, L01 groups (0.01 mg/ml and 0.1
      mg/ml) decreased the supernatant vWF level, and on the 48 h, high-dose group (0.1
      mg/ml) also decreased the supernatant vWF level, with significant difference
      compared with adrenaline group (10 microg/ml, P < 0.05). CONCLUSION: L01
      presented the protective effect on vascular endothelial cell.

PMID- 21179754
TI  - [Determination of maternal serum alpha-fetoprotein and free beta human chorionic
      gonadotropin in twin pregnancies comparing to single pregnancies in the second
      trimester].

PMID- 21179755
TI  - [Intervention of nutritional status and hypoxia endurance by a nutritional
      supplement in young adults living at high altitude].
AB  - AIM: To investigate the effects of a nutritional supplement on nutritional status
      and hypoxia endurance in young adults living at high altitude. METHODS: Forty
      healthy male young adults were recruited and randomly assigned to control and
      intervention groups. The nutrition survey was carried out using weighing method.
      The intervention group was given a nutritional supplement specifically designed
      for use at high altitude, while the control group was treated with a supplement
      made of stir-fried flour. After 20 days of supplementation, they marched from the
      altitude of 3700 m to 5100 m. The changes in HR, SaO2, serum concentrations of VA
      and VB2 and some minerals were measured. RESULTS: The results of nutrition survey
      showed that the ratio of three macronutrients was not adequate and the intakes of
      calcium, VA and VB2 were below Chinese RNI. The serum concentrations of calcium,
      magnesium and VA were below normal references. The serum VB2 concentration was at
      the low level o f normal reference. The nutritional supplement could increase the
      serum concentrations of calcium, magnesium, VA and VB2, indicating an improved
      nutritional status. The changes in HR and SaO2 were diminished in intervention
      group compared with control group. CONCLUSION: The nutritional supplement can
      improve nutritional status and increase the hypoxia endurance in young adults
      living at high altitude.

PMID- 21179756
TI  - [Sema4C expresses in neural stem cells].

PMID- 21179757
TI  - [Effects of ginkgolide B against damage of cultured hippocampal neurons caused by
      glutamate].
AB  - AIM: To investigate protective effects of ginkgolide B (GB) in different
      administration modes on glutamate-induced neuronal damage. METHODS: Essential GB
      were obtained by supercritical CO2 fluid extraction. Glutamate excitotoxicity
      were examined in primary cultures from neonatal Wistar rat, by using of Trypan
      blue dye staining, testing the lactate dehydrogenase leakage from cultured
      neurons and terminal deoxynucleotidyl transferase-mediated nick end labeling
      (TUNEL) method. The protective effects of GB in different administration modes
      (pre-treatment and post-treatment) were adopted and compared with the NMDA
      receptor uncompetitive antagonist-MK-801 in acute-treatment. RESULTS: Treatment
      with GB in two administration modes both could increase ratio of surviving
      neuron, decrease LDH efflux and reduce ratio of neuron apoptosis in different
      degree, depended on dose in certain range. The protective effect of pre-treatment
      was superior to post-treatment, but inferior to MK-801. CONCLUSION: GB can
      protect neurons against glutamate damage, and preventive using has more
      efficiency. The potential mechanism of its neural protection may be not only
      related to PAF receptor. If the predominant protection effect of GB in
      pretreatment is considered, precautionary intervention to high-risk population
      could have more value.

PMID- 21179758
TI  - [Neural stem cells transplantation improved learning and memory abilities in
      Alzheimer's disease rat].
AB  - AIM: To investigate whether transplantation of neural stem cells can ameliorate
      learning and memory abilities in Alzheimer's disease (AD) rats. METHODS: Neural
      stem cells were isolated from dentate gyrus of hippocampus of newborn rats. After
      labeled with Hoechst33258, neural stem cells were grafted into the hippocampus of
      AD rats. 2 or 4 weeks post transplantation, the rats underwent behavioral testing
      using Y-maze trial. Fluorescence observation and immunohistochemistry were used
      after the rats were sacrificed. RESULTS: Neural stem cells grafted into
      hippocampus of AD rats could not only survive well, but also possessed the
      capacity of continuous proliferation and migrate along the hippocampus.
      CONCLUSION: Neural stem cells grafted into hippocampus of AD rats can not only
      survive well, possess the capacity of continuous proliferation, but also
      ameliorate memory defects in Alzheimer's disease rats.

PMID- 21179759
TI  - [Decrease of extracellular pH modulates the whole cell voltage-gated potassium
      currents in rat pulmonary artery smooth muscle cells].
AB  - AIM: To study the modulation of extracellular pH on the voltage-gated potassium
      currents (I(Kv)) in isolated pulmonary artery smooth muscle cells (PASMCs).
      METHODS: I(Kv) was recorded using whole-cell patch clamp technique under the
      external solutions with different pH. The electrophysiological characteristics of
      I(Kv) were then analyzed. RESULTS: (1) As compared to the normoxic group, I(K),
      decreased under acidic condition. When the extracellular pH were 7.0, 6.5, 6.0,
      the peak currents at a potential of +60 mV were inhibited by 16.93% +/- 2.47% (P
      < 0.01), 33.03% +/- 2.13% (P < 0.01), 41.59% +/- 6.53% (P < 0.01) respectively,
      and the current-voltage relationship (I/V) curve shifted to the right. (2) When
      the extracellular pH was 7.0, 6.5, 6.0, the voltage-depended Gk-Em was shifted to
      the direction of positive and the activation was sped up. CONCLUSION: The results
      suggest that with the development of hypoxic pulmonary vasoconstriction (HPV),
      extracellular pH may take part in the modulation of Kv channels partly, then make
      the cell depolarized and decrease the Kv currents, this will lead to open the L
      type calcium channel and contract the pulmonary artery smooth muscle. It may be
      one of the mechanisms that hypoxic leads to HPV and finally accelerate the
      development of HPV.

PMID- 21179760
TI  - [Effect of hypoxia preconditioning on the expression of Bcl-2 and Bax in the
      neonatal rats with hypoxic-ischemic brain damage].

PMID- 21179761
TI  - [Roles of the histaminergic receptors in the locus ceruleus in stress-induced
      carotid baroreflex resetting in rats].
AB  - AIM: To explore the roles of H1 and H2 receptors in the locus ceruleus (LC) in
      the carotid baroreflex (CBR) resetting resulted from foot-shock stress. METHODS:
      Male SD rats were divided into two groups (n=18) at random: unstressed and
      stressed group. The latter were subjected to unavoidable electric foot-shock
      twice daily for a week and each session of foot-shock lasted 2 hours. The left
      and right carotid sinus regions were isolated from the systemic circulation in
      all animals anesthetized with pentobarbital sodium. The intracarotid sinus
      pressure (ISP) was altered in a stepwise manner in vivo. ISP-mean arterial
      pressure (MAP), ISP-Gain relationship curves and reflex characteristic parameters
      were constructed by fitting to the logistic function with five parameters. The
      changes in CBR performance induced by stress and the effects of microinjection
      with histaminergic receptors antagonists into the LC on the responses of CBR to
      stress were examined. RESULTS: Stress significantly shifted the ISP-MAP
      relationship curve upwards (P < 0.05) and obviously moved the middle part of ISP
      Gain relationship curve downwards (P < 0.05), and decreased the value of the MAP
      range and maximum gain (P < 0.05), but increased the threshold pressure,
      saturation pressure, set point and ISP at maximum gain (P < 0.05). Microinjection
      of selective H1 or H2 receptor antagonist, chlorpheniramine (CHL, 0.5
      microg/microl) or cimetidine (CIM, 1.5 microg/microl) into the LC, significantly
      attenuated the above-mentioned changes in CBR performance induced by stress and
      the alleviate effect of CIM was less remarkable than that of CHL (P < 0.05). The
      responses of CBR under stress to H1 or H2 receptor antagonist generally occurred
      20 min after the administration and lasted approximately for 16 min.
      Microinjection with the same dose of CHL or CIM into the LC in the unstressed
      group did not change CBR performance significantly (P > 0.05). However,
      microinjection of CHL or CIM into the LC could not completely abolish the stress
      induced changes in CBR. CONCLUSION: The stress results in a resetting of CBR and
      a decrease in reflex sensitivity. The stress-induced changes in CBR may be
      mediated, at least in part, by activating the brain histaminergic system. The H1
      and H2 receptors in the LC, especially, Hi receptors may play an important role
      in the resetting of CBR under stress. The descending histaminergic pathway from
      the hypothalamus to LC may be involved in these effects. Moreover, the effects of
      stress on CBR also have other mechanisms.

PMID- 21179762
TI  - [Changes of expression and distribution of prohibitin in oxidative stressed
      cardiomyocyte and its biological significance].
AB  - AIM: To approach the expression of prohibitin in oxidative stressed
      cardiomyocytes. METHODS: The oxidative stress model was established by treating
      neonatal cardiomyocytes with H2O2. Injury of cardiomyocytes were evaluated by
      detecting the LDH activity and MTT cell survival rate.The expression level of
      prohibitin was examined via the Western-blotting. The ability of mitochondrial
      oxidative phosphorylation was determined by measuring ATP synthesis via H+ 
      ATPase. Mitochondrial membrane potential was detected by flow cytometry using
      Rhl23. RESULTS: LDH activity increased significantly after exposure to H202,
      while the cell survival rate decreased by 34.51%-65.5%. The contents of
      mitochondrial prohibitin in stress group was much higher than that in control
      group. At the same time, the ability of ATP synthesis decreased by 60% and
      mitochondrial transmembrane potential decreased too. CONCLUSION: Express of
      prohibitin in oxidative stress cardiomyocytes was compensated increase.
      Prohibitin translocated to mitochondria after oxidative stress. Oxidative stress
      led to mitochondrial dysfunction.

PMID- 21179763
TI  - [The effect of intermittent moderate hypoxia on mouse nutritive metabolism].

PMID- 21179764
TI  - [Cardioprotective effects of NOS and PKC under hemin induced ischemia/reperfusion
      injury in rat hearts].
AB  - AIM: Whether hemin, a heme oxygenase 1 (HO-1) inducer, reduces
      ischemia/reperfusion injury and whether NO synthase (NOS) and PKC are involved in
      the cardioprotective effects were investigated in the present study. METHODS: The
      Langendorff model of isolated rat heart was used. The ventricular function,
      infarct size, LDH and CK during ischemia/reperfusion period were also observed.
      RESULTS: (1) After intraperitoneal injection of hemin (50 mg/kg) for 24 h, COHb
      concentration in rat blood enhanced. He-min preconditioning prevented the
      increase in LVEDP, decrease in LVDP and +/- dP/dt(max) in the isolated
      ischemia/reperfusion (ischemia for 30 main and subsequent reperfusion for 2 h)
      rat hearts. The leakage of LDH and CK in the coronary effluent was significantly
      declined in hemin-treated rat hearts. And the infarct size was als reduced. (2)
      By using an inhibitor of NOS NG-nitro-L-arginine methyl ester before the
      administration of hemin could inhibit the protection induced by hemin. (3)
      Administration of an inhibitor of protein kinase C chelerythrine (1 mg/kg) before
      hemin preconditioning could also abolish the cardioprotection induced by hemin.
      CONCLUSION: These data suggest that the involvement of NO synthase and protein
      kinase C have been implicated in hemin-induced delayed cardioprotection in
      isolated rat hearts.

PMID- 21179765
TI  - [The relationship between the effects of curcumin on cerebral
      ischemia/reperfusion injury and immediately genic expressions of fos, Jun and NF
      kappaB in hippocampal CA1 area and its significance in gerbils].
AB  - AIM: To explore the relationship between the effects of curcumin on cerebral
      ischemic/reperfusion injury and immediately genic expressions of Fos, Jun and NF
      kappaB in hippocampal CA1 area. METHODS: Gerbils were randomly divided into sham
      group (SH), ischemia/reperfusion group (I/R), curcumin group (CU) and solvent
      control group (SC). Forebrain ischemia was induced by occlusion of bilateral
      common carotid arteries. Observations were carried out in each group 15 min, 1 h,
      2 h, 6 h, 1 d, 3 d, 5 d and 7 d after ischemia: open field test was used to
      examine the behavioral change, the apoptosis neurons in hippocampal CA1 region
      was counted, the expression of Fos, Jun and NF-kappaB in hippocampal CA1 was
      detected by SABC immunocytochemical technique. RESULTS: The behavioral mark and
      the number of apoptosis neurons in hippocampal (CA1 region was much less in CU
      group than in I/R group (P < 0.01) The expression of Fos was more and the
      expression of Jun and NF-kappaB was less in CA1 area in CU group than in I/R
      group (P < 0.01). CONCLUSION: Curcumin can significantly protect neurons against
      cerebral ischemia, increasing the expression Fos and decreasing the expression of
      Jun and NF-kappaB may be the protective mechanisms.

PMID- 21179766
TI  - [The fluctuation of estrogen on the auditory evoked potential P50 in the rat
      striatum in estrus cycl].

PMID- 21179767
TI  - [Mechanisms of cardioprotection induced by preconditioning after activation of
      MITOK(ATP) channel].
AB  - AIM: To determine mechanisms of cardioprotection induced by combination
      angiotensin-converting enzyme inhibitors (ACEI) with subthreshold preconditioning
      after activation of mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel.
      METHODS: The Langendorff model of isolated rat heart was used. The time of the
      onset of uncoupling, the activities of sarcolemmal Na+/K+ -ATPase and Ca2+/Mg2+ 
      ATPase were measured. RESULTS: The subthreshold preconditioning (2 min of
      ischemia and 10 min reperfusion) or captopril (an ACEI) alone did not protect
      hearts against injury of sustained ischemia. However combination captopril with
      subthreshold preconditioning increased LVDP. Pretreatment hearts with mitoK(ATP)
      channel inhibitor 5-HD abolished the protection effect. Combination captopril
      with subthreshold preconditioning delayed the onset of uncoupling, and enhanced
      the activities of sarcolemmal Na+/K+ ATPase and Ca2+/Mg2+ -ATPase in
      ischemia/reperfusion hearts. But 5-HD cancelled these cardioprotection effects.
      CONCLUSION: Combination ACEI with subthreshold preconditioning delays the onset
      of cellular uncoupling induced by acute ischemia, and promotes the stability of
      sarcolemmal ion channels, in which activation of the mitoK(ATP) channels may be
      involved.

PMID- 21179769
TI  - [Evidence for the existence of P2X purinoceptors in the follicular oocytes of
      Xenopus laevis].

PMID- 21179768
TI  - [The alterations of nitric oxide synthase activity of ventricular cardiac muscle
      of rats in two septic shock models].
AB  - AIM: To observe the differences of hemodynamics and nitric oxide synthase(NOS)
      activity of ventricular cardiac muscle in two septic shock models and explore the
      possible mechanism. METHODS: Two rat models of septic
      shock[lipopolysaccharide(LPS)-induced and cecal ligation and puncture (CLP)
      induced septic shock] were used. The hemodynamic parameters and nitric oxide
      synthase activity of ventricular cardiac muscle were measured. RESULTS: The
      hemodynamic parameters in CLP-induced model were increased in the early stage and
      decreased in the late stage while in LPS-induced model the parameters showed the
      same change of the CLP late stage. Both LPS model and CLP model (late stage)
      showed significant increase in NOS activity, but there was no difference between
      the two models. After treatment of the NOS inhibitor N-nitro-L-arginine methyl
      ester (L-NAME), the parameters of CLP-late stage and LPS model increased
      significantly. The NOS activity reached the highest level in the CLP-middle
      stage. The production of nitrite/nitrate decreased significantly in LPS model and
      CLP model(late stage) after treatment of L-NAME, but the nitrite/nitrate produced
      by constitutive NOS in LPS model was higher than CLP model(late stage).
      CONCLUSION: The increase of the NOS activity may be the main reason to lead to
      the depression of the hemodynamic parameters. Inducible NOS may play the leading
      role in the LPS model while cNOS and iNOS have the same effect in the CLP model.

PMID- 21179770
TI  - [Dynamics of calcium in the hippocampal neuronal culture model of epilepsy].
AB  - AIM: To observe the intracellular calcium ion spatio-temporal and dynamic changes
      in the hippocampal neuronal culture model of epilepsy induced by low magnesium
      ion medium, and to explore the relationship between calcium ion and epilepsy.
      METHODS: Applying both laser scanning confocal microscope and patch clamp to
      timely observe the changes of [Ca2+]i and electrophysiological in the hippocampal
      neuronal culture model of epilepsy, and the influence of NMDA receptor-gated
      channels retarder and non-NMDA receptor-gated channels retarder. RESULTS: After
      the hippocampal nerve cell broken into epileptiform discharges, [(Ca2+]i rapidly
      ascended to (620 +/- 70) nmol/L, NMIDA acceptor retarder (MK-801, 10 micromol/L)
      and non-NMDA acceptor retarder (NBQX, 10 micromol/L) reduced [Ca2+]i ascendance.
      Recovery of the elevated [Ca2+]i was obviously delay, after 90 min and 150 min
      epileptiform discharges, it took (114.8 +/- 5.2) min and (135.0 +/- 22.7) min (P
      < 0.05) respectively. CONCLUSION: In vitro status epilepticus causes sustained
      elevation of intracellular calcium levels in hippocampal neurons

PMID- 21179771
TI  - [Treatment with interleukin-2 ameliorates endothelium-dependent vasorelaxation of
      aorta in streptozotocin-induced diabetic rats].
AB  - AIM: To investigate the changes in aortic functions in streptozotocin(STZ)
      induced diabetic rats and the effect of interleukin-2 (IL-2) on them, we observed
      the vasorelaxation of aorta to acetylcholine(ACh) and sodium nitroprusside(SNP).
      METHODS: Male Sprague-Dawley rats were randomly divided into a normal control
      group, an IL-2 control group, a diabetic group, and diabetic groups administered
      with a low dose (5 x 10(3) U x kg(-1) x d(-1), s.c.) or a high dose of IL-2 (5 x
      10(4) U x kg(-1) x d(-1), s.c.) for five weeks. Aortic rings were isolated for
      use in vitro isometric force recording studies, and endothelium-dependent
      relaxation induced by ACh and endothelium-independent relaxation induced by SNP
      were measured. The serum nitric oxide (NO) levels and the activities of serum
      superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were measured.
      RESULTS: ACh caused a dose-dependent relaxation that was weakened in the diabetic
      group. The IL-2 treated groups were less weakened. However, the endothelium
      independent relaxation induced by SNP was not significantly different in aortae
      of all groups. The serum NO levels were significantly increased in diabetic rats
      treated with IL-2 when compared with diabetic group, but the serum SOD and GSH-PX
      activities were not improved in diabetic group with IL-2. CONCLUSION: IL-2 can
      improve the aortic endothelium-dependent relaxation in diabetic rats, which
      involved the improvement of endothelial function in aorta, other than the
      alteration of anti-oxidative capacity.

PMID- 21179772
TI  - [Effect of propofol on iNOS expression in hippocampus after global cerebral
      ischemia/reperfusion injury of rats].

PMID- 21179773
TI  - [Effects of CGRP on LPS-induced MMP-9 secretion by alveolar macrophages].
AB  - AIM: To explore the effects of calcitonin-gene-related peptide (CGRP) on LPS
      induced MMP-9 secretion by alveolar macrophages (AM) in vitro. METHODS: The
      supernatant of LPS-induced Wistar rat AM from different intervention groups were
      collected to measure the activity by gelatin zymography. RESULTS: (Only secreting
      a small amount of MMP-9 with unstimulated AM, LPS stimulated MMP-9 production in
      a concentration-dependent manner (p < 0.01). (2) The activity of MMP-9 in CGRP
      intervention groups at different levels were significantly lower than those in
      non-intervention group (p < 0.01). (3) The inhibiting effects of CGRP were
      diminished by H-7 and W-7, an antagonist of protein kinase C (PKC) and calmodulin
      (CaM) (p < 0.05). CONCLUSION: These data suggested that CGRP involved in the MMP
      9 secretion by AM, partly, via PKC and CaM pathway.

PMID- 21179774
TI  - [Natriuresis induced by brain cholinergic stimuli and the change of ChAT-iR in
      kidney].

PMID- 21179775
TI  - [Effect of acute exhaustive exercise on gastrointestinal transit rate and
      nitrergic nerves in myenteric plexus in rats ileum].
AB  - AIM: To investigate the effect of acute exhaustive exercise on gastrointestinal
      motility and its enteric nervous mechanisms. METHODS: 24 rats were randomly
      divided into control group (C) and acute exhaustive exercise group (AEE). The
      rate of gastrointestinal transit was measured and histologic changes of
      nitriergic nerves in ileum myenteric plexus were observed with enzymatic
      histochemical and image analytic technique. RESULTS: In the rats of AEE group,
      the rate of gastrointestinal transit was delayed comparing with C group (P <
      0.05), the numbers of nitrergic neurons and expression levels of nitric oxide
      synthase (NOS) in the ileum myenteric plexus significantly increased comparing
      with C group (P < 0.01). CONCLUSION: It is possible that increase of nitrergic
      neurons and expression levels of NOS in the myenteric plexus of small intestine
      are one of the mechanisms of delay of gastrointestinal transit rate in acute
      exhaustive exercise rats.

PMID- 21179776
TI  - [Effect of protooncogene c-myb on progesterone-induced mouse germinal vesicle
      stage oocyte maturation in vitro].
AB  - AIM: To investigate the effects of c-myb on progesterone-induced mouse germinal
      vesicle(GV) stage denuded oocyte (DO) maturation in vitro. METHODS: We used mouse
      GV stage oocyte cultured with special concentration progesterone, or/and
      antisense c-myb ODN, or/and db-cAMP, or/and heparin for 24 h, and observed oocyte
      maturation and analysed the relationship among them. RESULTS: We cultured DO in
      the medium 199 for 24 h, and found 10 micromol/L progesterone had more
      significant effect than 5 micromol/L progesterone (2 h GVBD% P < 0.05, 8 h PB 1%
      P < 0.05), but had not more significant effect than 20 micromol/L progesterone.
      We found that 16 micromol/L antisense c-myb ODN significantly inhibited
      progesterone (10 micromol/L)-induced mouse germinal vesicle stage oocyte
      maturation in vitro (2 h GVBD% P < 0.05, 8 h PBI% P < 0.01). 1 x 10(-4)
      micromol/L dbcAMP, 100 microg/ml heparin could single significantly inhibited
      progesterone-induced mouse GV stage oocyte maturation in vitro (2 h PBI% all P <
      0.01, 8 h PBI% all P < 0.01), and could enhanced the inhibition of 16 micromol/L
      antisense c-myb ODN (2 h GVBD% all P < 0.01, 8h PBI% all P < 0.01). CONCLUSION:
      Progesterone, protooncogene c-myb,cAMP and calcium all pay important role in
      regulating oocyte maturation and the mechanism of progesterone, cAMP and calcium
      in regulating oocyte maturation may be through the expression of protooncogene c
      myb.

PMID- 21179777
TI  - [Effects of exposure to simulate unpressurised and dry state of disable submarine
      on the distributions of CD55 and CD59 on blood cellular membrane].

PMID- 21179778
TI  - [Identification of genes that are differentially expressed in omental fat of
      normal weight subjects, obese subjects and obese diabetic patients].
AB  - AIM: To identify genes that are differentially expressed in omental fat of normal
      weight subjects, obese subjects and obese type 2 diabetic patients. METHODS:
      Using a home-made high-density cDNA microarray, we compared gene expression
      profile of omental fat from normal weigh subjects, obese subjects and obese type
      2 diabetic patients, to identify adipose-specific genes associated with obesity
      and diabetes. RESULTS: 119 and 257 genes were up-regulated in obese patients and
      obese diabetic patients respectively, while 46 and 58 genes were down-regulated
      in obese patients and obese diabetic patients respectively. 77 genes, including
      metabolism related genes (PDK4), and caveolin 2, metallo thionein 1B, were up
      regulated in both obese and obese diabetic patients, while 8 genes, including key
      enzymes in lipid synthesis, such as HMG-CoA synthase, fatty acid synthase and
      stearoyl-CoA desaturase, were down-regulated in both groups. Another interesting
      finding was that tyrosine-3-monooxygenase/ tryptophan 5-monooxygenase activation
      protein theta (YWHAZ), a negative regulator for insulin signal transduction, was
      up-regulated only in obese diabetic patient, but not in normal-glycemic obese
      subjects. CONCLUSION: Our study demonstrated that decrease of lipogenesis along
      with increase of fatty acids oxidation of adipose tissue could be a common cause
      of insulin resistance in obesity and type 2 diabetes, while functional changes of
      other genes, such as immune regulation genes,might also be involved in the
      pathogenesis of obesity and type 2 diabetes. Block of insulin signal transduction
      might trigger the transition from obesity to diabetes. Further exploration of
      these genes will greatly help us in the understanding of the pathogenesis of
      obesity and type 2 diabetes.

PMID- 21179779
TI  - [Protective effect of 3,6-dimethylamino-dibenzopyriodonium gluconate on the
      injury of myocardial cells].

PMID- 21179780
TI  - [Effects of vitamin E on expression of PS-1 and production of Abeta in the
      hippocampus of female senile rats].
AB  - AIM: To observe the expression of Presenilin-1 (PS-1) and production of amyloid
      beta-protein (Abeta) in hippocampus of female senile rats and to investigate the
      effect of vitamin E(VE) on preventing Alzheimer's disease after menopause.
      METHODS: The animal model was established using female senile rats. Experimental
      groups (n=8) were respectively given different doses of VE(5 mg/kg, 15 mg/kg, 60
      mg/kg) per day. The expression of PS-1 in hippocampus was detected by
      immunohistochemistry, the level of Abeta in hippocampus was measured by
      Radioimmunoassay, and neuronal ultrastructure in hippocampal DG area was observed
      using transmission electron microscope. RESULTS: The expression of PS-1 in rat
      hippocampus of senile control group was stronger than that of adult control
      group. PS-1 expressed weakly in three medication groups along with augmentation
      of dosage. The levels of Abeta were found to correlate statistically with the
      expression of PS-1. The content of Abeta in VE groups was significantly decreased
      compared to that in senile control group (P < 0.01). There were some changes in
      the neuronal ultrastructure of senile rats. Neurons were gradually recovered in
      VE groups. CONCLUSION: VE may depress the production of Abeta by regulating the
      expression of PS-1, reducing neuronal injuries. VE may play a role in neuronal
      protection.

PMID- 21179781
TI  - [Influence of recombined human growth hormone on sIgA and EGF in rats with
      obstructive jaundice].
AB  - AIM: To study the effect of the recombined human growth hormone(rhGH) on
      secretory immunoglobulin A (sIgA), epidermal growth factor (EGF) in rats with
      obstructive jaundice. METHODS: Sixty Wistar rats were randomly divided into four
      groups, sham-operated (group A), common biliary duct-ligated (group B), biliary
      duct-ligated plus rhGH-treat for one week (group C), biliary duct-ligated plus
      rhGH-treat for two weeks (group D), each group had 15 rats. Except group A, the
      rats of other groups were operated with biliary duct-ligated. Until two weeks
      after operation, the rats of group A and B were killed. After operation, the rats
      of group C were treated with rhGH hypodermic injection (0.75 U x kg(-1) x d(-1))
      for one week, and then killed. The rats of D group were treated with rhGH
      hypodermic injection (0.75 U x kg(-1) x d(-1)) for two weeks, and then killed.
      All procedures were performed aseptically. Total bilirubin (TB), alkaline
      phosphatase (ALP), prealbumin(PA), insulin-like growth factor (IGF-1), sIgA, EGF
      were measured. RESULTS: Compared with group A, in group B, C, D, serum level of
      PA, IGF-1 and sIgA, EGF level of gastric and intestinal juice were lower, but TB,
      ALP were higher, there were significant difference. Compared with group B, the
      rats with treatment of rhGH in group C and D had higher sIgA and EGF and lower
      intestinal bacterial translocation. CONCLUSION: In objective jaundice rats, rhGH
      can protect their hepatic function, intestinal physical-barrier function and
      immune-barrier function, and reduce intestinal bacterial translocation.

PMID- 21179782
TI  - [Effects of different temperature diet on weight, plasma glucose, plasma lipids
      and anti-oxidation in rats].

PMID- 21179783
TI  - [The effect of simvastatin on the regeneration of sciatic nerve with crush injury
      in rats].
AB  - AIM: To explore the effect of Simvastatin on the regeneration of sciatic nerve
      with crush injury in rats. METHODS: Animals were randomized into the following
      experimental groups: Simvastatin-treated, vehicle and sham-operated groups.
      Sciatic nerves with crush injury were performed. After surgery, the functional
      evaluation of nerve recovery, electrophysiologic assessment, histological
      assessment, serum IL-6 and lipid were performed. RESULTS: The toe spread index of
      Simvastatin-treated rats after operation was higher significantly than vehicle
      rats at 5 d and 8 d (P<0.05). CMAP was higher and NCV was faster (P < 0.05). The
      serum IL-6 at 5 d of post-operation was significant lower (P < 0.05). Total serum
      cholesterol of Simvastatin-treated animals was higher than that of other animals
      (P < 0.05) at 2 weeks of post-operation. The histological analysis showed that
      the numbers of myelinated axons and the thickness of myelin sheath of Simvastatin
      treated crush injury animals at 4 weeks of post-operation were more than that of
      vehicle animals. CONCLUSION: The present study showed that Simvastatin could
      promote the regeneration of the sciatic nerve after crush injury in rats, partly
      through inhibiting immune and inflammatory responses and making the balance of
      serum cholesterol during these processes.

PMID- 21179784
TI  - [Evaluation about measurement of mice tidal volume by measuring thoracic
      inflating volume].

PMID- 21179785
TI  - [A modified intracellular labelling technique for high-resolution staining of
      neuron in 500 microm-thickness brain slice].
AB  - AIM: To develop simple but reliable intracellular labelling method for high
      resolution visualization of the fine structure of single neurons in brain slice
      with thickness of 500 microm. METHODS: Biocytin was introduced into neurons in
      500 microm-thickness brain slices while blind whole cell recording. Following
      processed for histochemistry using the avidin-biotin-complex method, stained
      slices were mounted in glycerol on special glass slides. Labelled cells were
      digital photomicrographed every 30 microm and reconstructed with Adobe Photoshop
      software. RESULTS: After histochemistry, limited background staining was
      produced. The resolution was so high that fine structure, including branching,
      termination of individual axons and even spines of neurons could be identified in
      exquisite detail with optic microscope. With the help of software, the neurons of
      interest could be reconstructed from a stack of photomicrographs. CONCLUSION: The
      modified method provides an easy and reliable approach to revealing the detailed
      morphological properties of single neurons in 500 microm-thickness brain slice.
      Without requisition of special equipment, it is suited to be broadly applied.

PMID- 21179786
TI  - [Effects of temperature on the burst opening of voltage-dependent K+ channels in
      hypothalamic neurons].
AB  - AIM AND METHODS: To observe the effect of temperature on burst opening of voltage
      dependent K+ channels(Kv) in hypothalamic neurons by cell-attached mode of patch
      clamp technique. RESULTS: With temperature raising, the number of burst opening
      increased, so did its average burst duration. B1 and B2 raised from 1.5 ms and
      6.6 ms at 32 degrees C to 8.1 ms and 83.2 ms (P < 0.05) respectively while the
      open number of inter-burst, from 1-2 to 8 (P < 0.05) too. Instead of SB, CB
      displayed predominantly a kind of burst opening. CONCLUSION: More burst opening
      of Kv in hypothalamic neurons with temperature raising, this was benefited to the
      body temperature regulation of neurons on hypothalamus.

PMID- 21179787
TI  - [Study of the effects of Bu Yang Huan Wu Tang on SOD and MDA brain tissue in
      cerebral ischemia and reperfusion of rats].

PMID- 21179788
TI  - [Ischemic tolerance of hippocampus induced by global ischemic preconditioning in
      rats].
AB  - AIM AND METHODS: To investigate the role of the duration of ischemic
      preconditioning and the interval between the ischemic preconditioning and the
      following injured ischemia in induction of ischemic tolerance of the hippocampus,
      using 4 vessel occlusion (4VO) global ischemic model of rats. RESULTS: Ischemia
      for 6 min resulted in a apparent delayed neuron death (DND) in the hippocampus,
      while ischemia for 3 min did not cause DND in the hippocampus. Ischemic
      preconditioning for 3 min could apparently decrease DND caused by ischemia for 6
      min followed the preconditioning at intervals of reperfusion 1 or 3 d (P < 0.01),
      indicating the protective effect of the ischemic preconditioning against the
      following severe ischemia. However, ischemic preconditioning for 1 min did not
      produce any apparent protective effect. The DND could not be decreased not only,
      but increased in a condition of ischemic preconditioning for 5 min followed by 6
      min injured ischemia at a interval of 1 d or ischemic preconditioning for 3 min
      followed by ischemia for 6 min at a interval of 1 h. CONCLUSION: Global ischemic
      preconditioning could induce tolerance of the hippocampus to ischemic injury. The
      proper duration of ischemic preconditioning and the interval between the
      preconditioning and the following injured ischemia might be 3 min and 1 to 3
      days, respectively, in the 4VO rat model.

PMID- 21179789
TI  - [Influence of eugenol on PEG2 and cAMP levels in PO/AH and arcuate nuclei in
      feverish rabbits].

PMID- 21179790
TI  - [Changes of the brain NSE, S100 and effect of ligustrazine in rats of chronic
      hypoxia and hypercapnia].
AB  - AIM: To investigate the changes of the brain NSE, S100 and ultrastructure and
      effect of ligustrazine in rats of chronic hypoxia and hypercapnia. METHODS:
      Thirty rats were randomly divided into three groups: control group (A), hypoxia
      hypercapnia group (B), hypoxia hypercapnia added ligustrazine group (C). The
      brain NSE, S100 and ultrastructure were observed in rats using the technique of
      immunohistochemistry and electronic microscope. RESULTS: (1) The mPAP was
      significantly higher in rats of group B than that of group A and it was much
      lower in rats of group C than that of group B. Differences of mCAP were not
      significant in three groups. (2) Serum NO of group B was significantly lower than
      that of group A, Serum NO of group C was higher than that of group B. (3)
      Immunohistochemistry showed the average value of integral light density (LD) of
      NSE and S100 was significantly much lower in rats of group B than that of group A
      and it was higher in rats of group C than that of group B. (4) The neuron and
      astrocyte of group B showed vacuolar degeneration and the myelin sheath showed
      separate. Damage of neuron is alleviated in rats of group C. CONCLUSION: The
      hypoxia hypercapnia could induce damage of neuron and astrocyte in rats. The
      ligustrazine may be useful in protecting against hypoxia hypercapnia brain
      damage.

PMID- 21179791
TI  - [Study of DNA damage with neuronal ischemia/reperfusion in vitro].
AB  - AIM AND METHODS: To investigate DNA strand damage in a model of cerebral
      ischemia/reperfusion injury in vitro, model of ischemia/reperfusion was produced
      by incubating the primary neuronal cultures to various durations of hypoxia and
      glucose deprivation (HGD). DNA single and double strand breaks were detected
      using PANT and TUNEL staining respectively. RESULTS: A few cell death occurred
      after 2 h of HGD. Less than 30 percent of cell died after 4 h of HGD, whereas 6-8
      h of HGD resulted in cell death in 80 percent of neurons. Neuronal cell death
      reached the peak 10-18 h after 6 h of HGD, while it took as early as 2 h after 8
      h of HGD. Following HGD, PANT positive cells were remarkably increased, which was
      proportional to the duration of HGD. At 5 minutes after 2, 4, 6 or 8 h of HGD,
      PANT positive cells were 30%, 50%, 80%, 90% respectively. Meanwhile, no
      determined in another cultures, DNA double strain breaks were not significantly
      increased. CONCLUSION: DNA strain breaks is a very early event of DNA damage
      following in vitro ischemia/reperfusion, especially DNA single strain breaks.

PMID- 21179793
TI  - [Mechanisms of morphine-evoked changes of intracellular calcium in primarily
      cultured hippocampal neurons].
AB  - AIM: In order to explore the neurobiological mechanism of morphine addiction and
      treatment methods, the acute and chronic effects of morphine on the intracellular
      free calcium concentration ([Ca2+]i) in cultured hippocampal neurons were
      investigated. METHODS: Changes of [Ca2+]i induced by morphine in primarily
      cultured hippocampal neurons were measured by confocal laser scanning microscopy
      using Ca(2+) -sensitive dye fluo-4 as the calcium fluorescent probe. RESULTS:
      Morphine actually induced the increase in [Ca2+]i of hippocampal neurons. This
      process could be blocked by naltrindole (delta opioid receptor antagonist)
      pretreatment, but not by CTOP (micro opioid receptor antagonist) pretreatment.
      Pretreatment of the cells with thapsigargin almost completely blocked morphine
      evoked response; while pretreatment of the cells with verapamil partially
      inhibited this response. After exposure to 100 micromol/L morphine for 24 h,
      intracellular [Ca2+]i increased and the increase could be intensified after
      adding 10 micromol/L naloxone to the medium. CONCLUSION: Morphine induced the
      release of Ca2+ is mainly from inositol 1, 4, 5-trisphosphate (IP3) sensitive
      stores in hippocampal neuron of rats through activation of delta2 subtype opioid
      receptor.

PMID- 21179792
TI  - [Experimental study of pituitary adenylate cyclase activating polypeptide on
      relieving brain edema induced by ischemia in rats].
AB  - AIM: In order to study the effects of pituitary adenylate cyclase activating
      polypeptide(PACAP) on brain edema induced by ischemia in rats and its underlying
      receptor mechanism. METHODS: Brain ischemia model in rats was established by
      ligaturing four--vessels. The percentage ratio of wet over dry tissue weight,
      sodium and potassium contents of dry brain tissue were measured by weighing and
      enzymatic analysis methods. RESULTS: The brain water contents significantly
      increased after rats exposed to 1 h of reperfusion following 30 - minute
      ischemia. Furthermore, sodium contents in brain tissue increased and potassium
      contents decreased following perfusion. Changes of brain water contents, sodium
      and potassium contents were relieved by lateral ventricular injection of PACAP in
      the concentration of 1 x 10(-9), 1 x 10(-10) or 1 x 10(-11) mol respectively
      before ischemia. The effect of PACAP could be blocked by MCAP6 - 38 (specific
      type I PACAP receptor antagonist) lateral ventricular injection prior to PACAP
      administration. CONCLUSION: Exogenous PACAP may act as a protective effect in
      brain edema induced by ischemia in rats, which is mediated by type I receptor.

PMID- 21179794
TI  - [Effect of electroacupuncture with different frequencies on neuropathic pain in a
      rat model].
AB  - AIM: Our previous studies showed that electroacupuncture (EA) could inhibited
      radiant heat induced pain and acute or chronic inflammatory pain in rats. In the
      present study, we observed whether EA with different frequencies could suppress
      neuropathic pain. METHODS: L5/L6 nerve ligation model was used to assess the
      effect of EA on neuropathic pain. Mechanical allodynia was represented by 50%
      withdrawal threshold, while cold-induced ongoing pain was detected by the number
      of paw lift in 5 min when the rat was put on a 5 degrees cold plate. Han's
      acupoint nerve stimulator (HANS) was connected to needles inserted into acupoints
      "jiaji" and "Zusanli" in both sides. The parameters were: (intensity: 0.5-1-2 mA,
      10 min each; frequency 2 Hz or 100 Hz; pulse width: 0.6 ms for 2 Hz, 0.2 ms for
      100 Hz). RESULTS: EA of both 2 Hz and 100 Hz could relieve the mechanical
      allodynia, where 2 Hz could induce the effect with shorter latency; they could
      also relieve the cold-induced ongoing pain, where the effect of 2 Hz outlasted
      the EA session by up to 48 h after repetitive stimulations over several weeks; a
      significant relieving effect on cold-induced ongoing pain could also be induced
      by needle insertion without stimulation. CONCLUSION: EA could relieve neuropathic
      pain, the analgesic effect of 2 Hz EA is higher than 100 Hz EA.

PMID- 21179795
TI  - [Effects of adrenergic receptor agonists injected into hippocampus on cellular
      immune function].
AB  - AIM AND METHODS: The effect of intrahippocampal microinjection of noradrenaline
      (NA) and its receptors antagonists and agonists on cellular immune functions were
      investigated in normal and adrenalectomy rat by determine the proliferative
      activity of Con A-stimulated splenic lymphocytes in MTT method and natural killer
      (NK) cell activity. RESULTS: (1) In normal group, the proliferative activity of
      Con A-Stimulated splenic lymphocytes were inhibited and the activity of NK cell
      were reduced with microinjection NA and beta1-, beta2-adrenergic receptor
      agonists Dobutamine (Dob, 4 microl, 6.0 x 10(-3) moL/L), Metaproterenol (Met, 4
      microl, 8.0 x 10(-3) mol/L), compared with their intensity of effect, NA > Met >
      Dob; the immunosuppression effect induced by NA was partly hindered by alpha- and
      beta-receptor antagonists, phentolamine (Phen, 2 microl, 1.6 x 10(-2) mol/L) and
      propranolol (Prop, 2 microl, 1.6 x 10(-3) mol/L), and the action of Prop was more
      evident. (2) In adrenalectomy group, immunosuppression effect induced by NA was
      unconspicuous. CONCLUSION: The results suggested that NA in hippocampus could
      inhibit distinctly cellular immune functions, which was predominantly mediated by
      beta2- adrenergic receptor with a minor contribution of beta1- and alpha-
      adrenergic receptors. Moreover, keeping intact construction and function of
      adrenal gland have an important role in the effect of NA on cellular immune
      function.

PMID- 21179797
TI  - [The research on monoamine neurotransmitters changes in plasma and cerebrospinal
      fluid in patients with persistent vegetative state].
AB  - AIM: To study the relationships between the pathogenesis of persistent vegetative
      state (PVS) and the levels of monoamine neurotransmitters in plasmas and
      cerebrospinal fluids (CSFs) in patients with PVS. METHODS: The high-pressure
      liquid chromatography (HPLC) was used to detect. RESULTS: It was found that the
      level of dopamine (1.95 +/- 0.99) was significantly increased in plasma compared
      with the control (1.16 +/- 0.47) (P < 0.05), but the levels of 5-HT, TYR, TRP,
      GABA of plasma were insignificantly changed. In cerebrospinal fluid, the level of
      DA was insignificantly changed, and the level of 5-HT (0.49 +/- 0.32) was
      significantly decreased compared with the control (1.02 +/- 0.35) (P < 0.05), but
      the levels of TYR (1.36 +/- 0.11), TRP (0.63 +/- 0.40), GABA (1.15 +/- 0.61) were
      significantly increased respectively compared with the controls (0.40 +/- 0.24;
      0.29 +/- 0.22; 0.37 +/- 0.45) (P < 0.05; P < 0.05; P < 0.01). The levels of GABA
      and DA in plasma were significant correlated (P < 0.05), and GABA and DA in CSF
      were also significant correlated (P < 0.01). CONCLUSION: The results of this
      study suggested that PVS is related to the decrease of 5-HT in CSF and the
      increase of DA in plasma.

PMID- 21179798
TI  - [Effects of baicalin on contents of PGE2 and cAMP in hypothalamus of fever rats].
AB  - AIM AND METHODS: Both PGE2 and cAMP are important neural mediator of fever. In
      order to discuss if PGE2 and cAMP are involved in the antipyretic mechanism of
      baicalin, fever models of rats were made by i.v. injection of endotoxin (ET). The
      antipyretic action and effects of baicalin on contents of PGE2 and cAMP in
      hypothalamus were observed. RESULTS: Baicalin possessed obvious antipyretic
      effect on fever rats and reversed the effect of ET on contents of PGE2 and cAMP
      in hypothalamus. Correlation analysis showed that contents of PGE2 and cAMP in
      hypothalamus were positively correlated with the change of body temperature of
      rats. CONCLUSION: Baicalin may exert its antipyretic effect on fever rats by
      inhibiting increase of contents of PGE2 and cAMP in hypothalamus.

PMID- 21179799
TI  - [The protection of vitamin E on LTP in hippocampal dentate gyrus of rats under
      stress].
AB  - AIM: To study the effects of vitamin E on stress-induced impairments in
      hippocampus of rats. METHODS: Twenty four male Wistar rats were randomly
      allocated into four groups: control, stress, control+ VE, stress+ VE. The rat
      stress model was built by restraining for 6 h/d,21 d. The long-term potentiation
      was induced in rat hippocampal dentate gyrus (DG) by high-frequency test
      stimulation. RESULTS: Compared with control group, the rats suffered from
      restraint stress showed that the number of crossing in open-field test and the
      content of glucocorticoids in plasma was significantly increased, the changes of
      amplitude of population spike (PS) were significantly lower. After VE
      supplementation in stress rats, the indices mentioned above were significantly
      improved. CONCLUSION: Opportune supplementation of vitamin E may improve the
      brain function under stress.

PMID- 21179800
TI  - [Activation of PACAP receptor could protect cultured hippocampal neurons against
      beta amyloid peptide induced neurotoxicity].
AB  - AIM: To observe the protective role of pituitary adenylate cyclase activating
      polypeptide (PACAP) on hippocampal neuronal apoptosis induced by beta amyloid
      peptide in the culture. METHODS: Hippocampal neurons were isolated from 1d old SD
      rat and neuronal survival and apoptosis were measured by MTT assay and DNA
      ladder. RESULTS: 25 micromol/L Abeta could induce neuron apoptosis while co
      treatment with PACAP could increase the survival of hippocampal neurons. The
      antagonist of PACAP receptor, P6-27, could reverse the effect of PACAP.
      CONCLUSION: PACAP could protects cultured neurons from the neurotoxicity of Abeta
      through the activation of PACAP receptor and may have a bright use in treatment
      of neurodegenerative disease.

PMID- 21179801
TI  - [Influence of cold exposure on some biochemical indexes and gastrointestinal
      tract mucosal hyperaemia in hailan chickens].

PMID- 21179802
TI  - [Effect and mechanism of interleukin-2 on the rhythm of isolated rat heart and
      neonatal myocytes].
AB  - AIM: To explore the effect and mechanism of interleukin-2 (IL-2) on the rhythm of
      isolated rat heart and neonatal myocytes. METHODS: Cultured neonatal rat
      cardiomyocytes and isolated perfused rat heart were used. RESULTS: (1) IL-2 (2.5
      200 u/ml) reduced the spontaneous beating rate of cultured neonatal rat
      cardiomyocytes in a dose-dependent manner. (2) IL-2 at 50 u/ml increased both the
      heart rate and the number of premature ventricular excitation in the isolated
      heart. (3) Pretreatment with propranolol abolished the effect of 50 u/ml IL-2 on
      the isolated heart. (4) Heat inactivated IL-2 had no significant effect on the
      cultured cardiomyocytes and isolated hearts. CONCLUSION: IL-2 inhibited the auto
      rhythmic of cultured cardiomyocyte directly while the positive chronotropic and
      arrhythmogenic effects of IL-2 in the isolated rat heart may be mediated by
      endogenous catecholamine.

PMID- 21179803
TI  - [Effect of NO on automaticity of rabbit sino-atrial node].
AB  - AIM: To investigate the effects of exogenous NO donors sodium nitroprusside (SNP)
      and 3-morpholinosydnonimine (SIN-1) on automaticity of the rabbit sino-atrial
      node in vitro and the action mechanism. METHODS: The intracellular microelectrode
      technique is used to record the action potentials of rabbit sino-atrial node and
      APA (amplitude of AP), V(max) (maximal rate of depolarization), VDD (velocity of
      diastolic depolarization), RPF (rate of pacemaker firing) are analyzed. RESULTS:
      SNP(10(-5) - 10(-2) mol/L) increased its RPF and VDD dose-dependently. 10(-3)
      mol/L SNP increased RPF (beats/min) from 163 +/- 10.8 to 195.0 +/- 13.1 increased
      VDD (mV/s) from 50.3 +/- 9.6 to 70.2 +/- 12.1 (P < 0.01). SIN-1(10(-3) - 10(-2)
      mol/L) also increased RPF and VDD (P < 0.01).10(-4) mo/L Methylene blue (MB), a
      blocker of GMP cyclase, prevented the positive chronotropic effect and
      increasement of VDD induced by 10(-3) mol/L SNP totally (P < 0.01). 2. CsCl (2
      mmol/L), a blocker of I(f) prevented the increasement of RPF and VDD in part (P <
      0.05). 3. NIF (0.46 micromol/L), a blocker of I(Ca-L, had no significant effects
      on chronotropic effect and increasement of VDD (P < 0.01). CONCLUSION: Exogenous
      NO can increase the automaticity of rabbit sino-atrial node in vitro. The
      chronotropic effect is involved in NO-cGMP pathway and results from increasement
      of I(f) in the sino-atrial node at least in part; I(ca-L) is unlikely to play a
      major role in this effect.

PMID- 21179804
TI  - [Effect of Puerarin on K+ channel of isolated ventricular myocyte in guinea pig].
AB  - AIM AND METHODS: To observe the effects of Puerarin on K+ channel of isolated
      ventricular myocyte in guinea pig. METHODS: Using inside-out configuration of
      patch-clamp single channel recording technique. RESULTS: Puerarin 20 micromol/L,
      40 micromol/L, 80 microml/L could inhibit the open-close rate of K+ channel of
      isolated ventricular myocyte in guinea pig. At 80 micromol/L, Po was decreased
      from 0.867 +/- 0.13 to 0.019 +/- 0.01 (n = 5, P < 0.05). CONCLUSION: Puerarin can
      inhibit K+ channel of isolated ventricular myocyte in guinea pig. It may be the
      mechanism of Puerarin against arrhythmias in molecular level.

PMID- 21179805
TI  - [Effect of taurine on thyroid hormone and second messenger in myocardium of rats
      after exhaustive exercise].
AB  - AIM: Probe into protective action of taurine against exercise-induced myocardial
      damage in rats after exhaustive exercise. METHODS: Using the model of exhaustive
      exercise, the present study researches into effects of taurine on the content of
      triiodothyronine (T3) and tetraiodothyronine (T4) in serum and myocardium as well
      as the activity of T(4) 5' deiodinase (T(4)5'-DI) and second messenger cAMP in
      myocardium of rats. RESULTS: The content of T3 in serum and myocardium, T(4)5'-DI
      activity, second messenger cAMP in myocardium increased significantly (P < 0.01)
      while that of T4 in serum and myocardium did not change significantly after
      exhaustive swimming. The supplement of taurine might significantly inhibit above
      changes caused by exhaustive exercise. CONCLUSION: Taurine could protect
      myocardium from exhaustive exercise induced damage by inhibiting hypermetabolism
      of thyroid hormone and change of second messenger.

PMID- 21179806
TI  - [1, 25-Dihydroxyvitamin D3 increases in vitro vascular calcification through
      calcified blood vessel cells].
AB  - AIM: Accumulated evidence suggest that the development of vascular calcification
      is similar to osteogenesis. Here we want to elucidate the effect of the common
      used osteo-regulatory factor 1,25(OH)2D3 on vascular calcification. METHODS AND
      RESULTS: Adding 10(-9) mol/L to the culture media 1,25(OH)2D3 time dependently
      increased the calcium deposition on the in vitro calcification of bovine vascular
      smooth muscle cells (BVSMCs) induced by beta-GP. It also increased cellular
      alkaline phosphatase activity by 301.1% during the calcified process.
      Osteocalcin, one of the osteogenic specific metric proteins, was dramatically
      elevated by 58.3% during the calcified processes, which indicate the
      transformation of BVSMCs to osteoblastic cell. 1,25(OH)2D3 had no such effect on
      non-calcified BVSMCs. CONCLUSION: These data suggest that 1,25(OH)2D3 exerts a
      stimulatory effect on vascular calcification through increasing the synthesis of
      ALP. This effect shares the same character as osteoblast cells. This effect is
      limited to the calcified prone vascular cell.

PMID- 21179807
TI  - [TGF-beta and HSP70 expression in human skin fibroblasts after ultraviolet B
      irradiation].
AB  - AIM AND METHODS: For further understanding the signal transduction pathway of the
      inducible HSP70 expression the expression of TGF-betamRNA and HSP70 in
      fibroblasts after 5, 10 and 20 mJ/cm2 of UVB irradiation, and the content of TGF
      beta protein in culture supernatants and HSP70 expression in fibroblasts by
      10mJ/cm2 UVB irradiation after preincubation with the anti-human TGF-beta
      receptor II antibody were observed. RESULTS: (1) TGF-betamRNA expression
      positively correlated with HSP70 expression in UVB irradiation of different doses
      (r = 0. 906). (2) TGF-beta content in the culture supernatants negatively
      correlated with the HSP70 expression induced in adding anti-human TGF-beta
      receptor II antibody and UVB treatment condition (r = - 0.995). CONCLUSION:
      TheTGF-beta play an important action in HSP70 inducing by UVB irradiation.

PMID- 21179808
TI  - [Effects of clenbuterol on the metabolism of nitrogen and IGF-I level in isolated
      perfused rat liver].
AB  - AIM: To examine the liver mechanism with which clenbuterol is explained how to
      affect growth metabolism. METHODS: Twenty-four adult SD rats were randomly
      divided into three groups, a control and two treatment groups. The technique of
      isolated perfused rat liver in vitro was used to study the effects of clenbuterol
      on urea nitrogen concentration of perfused medium, GPT activity and synthesis and
      secretion of IGF-I in isolated perfused rat liver. RESULTS: Urea-nitrogen
      concentration of perfused medium was significantly affected by clenbuterol in a
      dose-dependent and time-dependent manner. The urea-nitrogen level was decreased
      by 15.02% (P > 0.05),17.97% (P > 0.05), 26.76% (P < 0.05) and 30.08% (P < 0.01)
      for 1 h, 2 h, 3 h, 4 h after administering clenbuterol at the dose of 1 x 10(-6)
      mol/L, respectively, compared to that of control. 1 x 10(-8) mol/L CL had the
      similar effect on urea-nitrogen level. GTP activity of isolated perfused rat
      liver was inhibited by clenbuterol. The enzyme activity was decreased by 24.65%
      (P < 0.05) at the dose of 1 10(-6) mol/L CL in clenbuterol-treated 4h. The
      production and secretion of IGF-I were also influenced by clenbuterol in isolated
      perfused rat liver. IGF-I concentration of rat liver was increased by 19.77% (P <
      0.05) in 4 h clenbuterol treatment (1 x 10(-6) mol/L). Meanwhile, IGF-I
      concentration of perfusion medium was also elevated though the difference was not
      significant compared with control. CONCLUSION: It is suggested that clenbuterol
      may improve growth metabolism by means of increasing nitrogen retention and
      enhancing IGF-I production and secretion of rat liver.

PMID- 21179809
TI  - [Research of resisted function of L-arginine on BP in stress rats].

PMID- 21179811
TI  - [Effect of sex hormones on secretion of lysozyme in alveolar macrophage].
AB  - AIM AND METHODS: To further explore the functions of alveolar macrophage and
      their modulation mechanisms, the activity of lysozyme in rat alveolar macrophage
      assessed by electrophoresis was determined. The effects of androsterone and
      estradiol on lysozyme secretion and their mechanisms were also studied. RESULTS:
      The results showed that androsterone and estradiol increased activity of lysozyme
      significantly (P < 0.01), indomethacin abolished those effects. This suggests
      that the insufficiency of sex hormones secretion as the retrogression of gonads
      is involved in the decrease of immunological functions, and the susceptibility to
      infectious diseases. CONCLUSION: Sex hormones increased activity of lysozyme, and
      those effects related to prostaglandin.

PMID- 21179810
TI  - [Effects of ligustrazin on lipid peroxidation during hepatic ischemia reperfusion
      injury].
AB  - AIM: To explore the role of ligustrazin on dynamic changes of lipid peroxidation
      in hepatic ischemia/reperfusion injury (HIRI) and its mechanism. METHODS: The
      HIRI model was used. Twenty rabbits were randomly divided into control group (n =
      10) and ligustrazin group (n = 10). The xanthine oxidase (XO) activity,
      superoxide dismutase (SOD) activity,malondialdehyde (MDA) content and glutamic
      pyruvic transaminase (GPT) activity in plasma were observed before ischemia and
      at ischemia 25 min, reperfusion 25 min, reperfusion 60 min and reperfusion 120
      min. RESULTS: The XO activity, SOD activity, MDA content and GPT activity of
      ligustrazin group, as compared with control group, showed significant differences
      (P < 0.05 or P < 0.01) at total time points of reperfusion. CONCLUSION:
      Ligustrazin has notable anti-lipid peroxidation effect on HIRI, which is due to
      its inhibiting the generation of oxygen free radicals and its strengthening
      scavenging of oxygen free radicals.

PMID- 21179812
TI  - [Heat shock response in guinea pigs cochlea with gentamicin ototoxicity].
AB  - AIM: To explore the effects of gentamicin ototoxicity on the expression of heat
      shock protein 70 in guinea pigs cochlea. METHODS: We used immunohistochemistry
      staining and image quantitative analysis system, combined with auditory brainstem
      response (ABR) measurement to investigate the change on the expression of HSP70
      in guinea pigs cochlea of gentamicin ototoxicity. RESULTS: The levels of HSP70
      immunoreactivity in guinea pigs cochlea of experimental animals were high
      including Corti's organ, stria vascularis, medial spiral limbus, spiral ganglion
      cells and the threshold of ABR was in high correlation with the expression of
      HSP70 ([ r] > 0.8, P < 0.01). CONCLUSION: Gentamicin can induce expression of HSP
      70 in guinea pigs cochlea and protect hearing function.

PMID- 21179813
TI  - [Overlapping properties of blood supplication of medulla by medullary branches of
      basilar artery in cats].

PMID- 21179814
TI  - [Effects of cryopreservation length on the proliferative potential of cord blood
      hematopoietic cells in vitro].
AB  - AIM: To study the effects of cryopreservation length on the proliferative
      potential of hematopoietic cells derived from cord blood. METHODS: Using Dextran
      40 and 10% DMSO as cryoprotectants, separated nuclear cells were stored in liquid
      nitrogen after they were freezed according programme. One month or 4 months
      later, they were thawed and expanded in serum-free medium for culture and
      expansion of hematopoietic cell (SFEM) for 5 weeks. Dynamic results were detected
      every week. RESULTS: At the 5th week of expanding, TNC were expanded for 1499.0
      +/- 115.6-folds and 1513.0 +/- 110.4-folds, respectively. CD34+ cells and CFCs
      reached to their highest level at the 2nd week and at the 3rd week. CD34+ cells
      were expanded for 63.8 +/- 6.1-folds and 62.4 +/- 5.7-folds, respectively. CFCs
      were expanded for 53.8 +/- 6.3-folds and 54.8 +/- 6.7-folds, respectively.
      Between the two kinds of cells, statistical significant difference in
      proliferative potential wasn't detected. CONCLUSION: In ideal cryopreservative
      condition, the cryopreservation length would do not affect the proliferative
      potential of cord blood hematopoietic cells.

PMID- 21179815
TI  - [Effects of different temperature and time on the quality of blood preservation
      in liquid blood].
AB  - AIM: To explore the effects of different temperature and time on preservation
      damages in liquid blood. METHODS: Take blood sample from 10 healthy blood donors,
      put the fresh blood into CP2D-A liquid at 0 degrees C and 4 degrees C, and take
      the samples after 1 week, 2 weeks and 3 weeks, and then measured the contents of
      GSH-Px, TSH, LPO, the contracting protein of RBC, and membrane fluidity. RESULTS:
      At the same temperature, when the preservation time is prolonged, peroxidation is
      increased, the preservation damages are also augmented; the damages are declined
      when the temperature is lower during the same period, the aging of blood was more
      evident at 4 degrees C. CONCLUSION: Blood peroxidation temperature is lower. The
      0 degrees C group is better than 4 degrees C group.

PMID- 21179816
TI  - [The expression of mRNAs encoding subunits of NMDA during postnatal development
      in rat inferior colliculus].

PMID- 21179818
TI  - [Zymography identification of the matrix metalloproteinases synthesized by
      cultured hepatic stellate cells].
AB  - AIM: To establish a method for identification of the activities of matrix
      metalloproteinases (MMPs) synthesized by cultured hepatic stellate cells (HSC).
      METHODS: SDS-gelatin polyacrylamide gels electrophoresis was used for the
      identification of MMPs synthesized by cultured HSC. RESULTS: MMP-2 and MMP-9 in
      culture medium and HSC were sensitively identified, and MMP-2 activity was higher
      than MMP-9 in culture medium, the changes of MMPs in culture medium and HSC were
      also observed after 24h medicine treatment. CONCLUSION: Zymography is suitable
      for the studies on the role of HSC in the regulation of extracellular matrix
      turnover.

PMID- 21179817
TI  - [A simple and convenient method for assaying human RBCs glycolysis rate without
      oxygen].
AB  - AIM: To convenience of the methods for assaying red blood cell glycolysis without
      oxygen condition in the studies. METHODS: Reagent kit of glucose, perchloric
      acid, visible light prismatic photometer, battle of nitrogen and rocking bed are
      used in the studies. The process includes 4 steps prepare Tris- HCI solution and
      so on, assay of red blood cell glycolysis without oxygen condition and account of
      glycolysis rate. RESULTS: Human red blood cells stored at 4 degrees C for 75 d,
      in SOD solution, the glycolysis rate is 86.2% +/- 5.0%, distinctly better than
      GMA solution (39.2% +/- 8.9%). CONCLUSION: The methods of assaying glycolysis
      without oxygen condition not use Habea's apparatus. The operation is convenient
      and simple and its determinations can be performed in ordinary laboratory and is
      is accurate.

PMID- 21179819
TI  - [Determination of reactive oxygen species in mitochondria by fluorometric probe].
AB  - AIM AND METHODS: Based on the reaction that 2',7'-dichlorodihydrofluorescein
      (DCFH) can be oxidized by reactive oxygen species (ROS) to yield the highly
      fluorescent 2',7'-dichlorofluorescin (DCF), ROS production in mitochondria can be
      observed dynamically as well as quantified directly by spectrofluorometer.
      RESULTS AND CONCLUSION: DCF fluorescence showed linear increase in State 4
      mitochondria, which suggest ROS produced at constant rate. The slopes of the
      linear increase in fluorescence with time were computed performing a linear
      regression that took into account all relevant data points in selected time
      windows. The slopes were proportional to ROS production in mitochondria. Addition
      of sodium azide and malonic acid increased and decreased the rate of ROS
      production respectively during measurement. DCF fluorescence varied linearly with
      increasing concentration of mitochondria, which showed quantitative relations in
      definite range. Repeated measures showed low coefficients of variation. This
      method is reliable and efficient for determining ROS in mitochondria.

PMID- 21179820
TI  - [Method of recording intestine electric and motility activity with recording
      electrode superposition on strain gauge].
AB  - AIM: In order to decrease the destruction on the intestine wall, increase the
      same pace of the recording electric and mechanic activity and make the method
      simple during recording of intestine activity. METHODS: Silver ball electrode was
      held upon the strain gauge plate by silica gel which was a 2 mm 5 mm 9 mm
      recording device to be sewed only through the four corner point on to the
      intestine. RESULTS AND CONCLUSION: It had little destruction on the intestine and
      was more easy and the recording electric activity was in almost the same pace of
      the motion.

PMID- 21179821
TI  - [Evaluation of pulmonary microvascular permeability in isolated perfused rabbit
      lungs].
AB  - AIM: To quantity and accurately evaluate pulmonary microvascular permeability.
      METHODS: To measure capillary fluid filtration coefficient (Kf) by using the
      gravimetric method in isolated perfused rabbit lungs. RESULTS: The amount of Kf
      is 4.78 +/- 0.73 mg x min(-1) x cmH2O(-1) x g(-1). CONCLUSION: The advantage of
      this method is exactly and directly. This method shows the important effect on
      realizing the pulmonary physiologic condition and evaluating the extent of acute
      lung edema and injury.

PMID- 21179823
TI  - [Culture of airway smooth muscle cells from human].

PMID- 21179822
TI  - [Changes of myocardial mitochondrial Ca2+ transport and effects of ATP on them in
      the early stage after severe burns].

PMID- 21179824
TI  - [Change of GABA immunoreactivity in area tempestas of epileptic sensitive rats].

PMID- 21179825
TI  - [Protein synthesis and characterization in isolated mitochondria from rat brain].
AB  - AIM: To establish a system of mitochondrial translation in vitro of rat brain and
      identify it's production of protein by molecular weight. METHODS: Mitochondria
      isolated from hemisphere of rat brain by differential centrifugations. The
      optimization of mitochondrial translation in vitro by 3H-Lencine incorporation
      was explored. 35S-methionine labeled products of mitochondrial protein synthesis
      were identified by SDS-PAGE and fluorography. RESULTS: Isolated mitochondria had
      a highly activity oxidative phosphorylation and respiratory control ratio (RCR)
      was between 3.5 and 5.5. The activity of 3H-Lencine incorporation in isolated
      mitochondria in vitro increased with time of incubation in 60 min and maintained
      a steady level. The maximal activity of 3H-Lencine incorporation per milligram
      mitochondria protein occured at 1 mg mitochondria/ml of incubation mix.The major
      auto radiographic bands could be observed at 86, 68, 56, 43, 33, 29, 25 and
      18(kD) molecular weight separated on SDS-PAGE. CONCLUSION: The translation system
      of rat brain mitochondria in vitro is faithful and high activity, can be used to
      study mtDNA expression and regulation in mammalian brain at the level of
      translation.

PMID- 21179826
TI  - [The effect of nitric oxide on electroacupuncture analgesia in central nervous
      system of rats].

PMID- 21179827
TI  - [Research of regulation on calcium-activated potassium channel in hypothalamic
      neurons by nitric oxide].
AB  - AIM: To study the effects of nitric oxide on calcium-activated potassium channels
      (KCa) in hypothalamus neurons. METHODS: The data was recorded by adopting cell
      attached or inside-out configuration of patch-clamp technique. RESULTS: Nitric
      oxide was found to increase the open probability of the channels directly or
      through increasing cGMP, which resulted from both the prolongation of open period
      and increase of open frequency. CONCLUSION: Nitric oxide could regulate calcium
      activated potassium channels in hypothalamic neurons through alternative
      pathways.

PMID- 21179828
TI  - [Roles of ACh receptors in the effects of corticosterone on presympathetic
      neurons in the ventrolateral medulla of rats].
AB  - AIM: To investigate the roles of acetylcholine (ACh) receptors in the rapid
      effects of corticosterone (CORT) on the presympathetic neurons in the rostral
      ventrolateral medulla (RVLM) of rats, and study the non-genomic mechanism of
      glucocorticoid (GC) in the integration of sympathetic cardiovascular activity.
      METHODS: The effects of microelectrophoresis of CORT on the discharge of the
      presympathetic neurons in the RVLM were observed by extracellular recording in
      urethane-anaesthetized rats. The responses of atropine (a blocker for M type of
      ACh receptor, ATR), d-tubocurarine (a blocker for N1 type of ACh receptor, d-TC)
      and hexamethonium (a blocker for N2 type of ACh receptor, C6) to the effects of
      CORT on the presympathetic neurons were investigated respectively. RESULTS:
      Totally 33 presympathetic neurons in the RVLM were recorded. Among them the
      firing rate of 25 (76%) presympathetic neurons was increased by
      microelectrophoresis of CORT. The effects of CORT were also positively correlated
      with the currents. In the other 8 presympathetic neurons, had was shown no effect
      after microelectrophoresis of CORT. In 10 presympathetic neurons, which discharge
      was increased by CORT, microelectrophoresis of ATR decreased the firing rate of
      these presympathetic neurons (P < 0.05), and did not fully block the excitatory
      effect induced by CORT. In both 7 and 6 presympathetic neurons, application of d
      TC and C6 had no effect on these neurons respectively, and did not fully block
      the excitatory effect induced by CORT. CONCLUSION: CORT had rapid excitatory
      effects on the presympathetic neurons in the RVLM, which effect might be
      independent on ACh receptors.

PMID- 21179829
TI  - [The apoptosis of adult cardiomyocytes induced by ischemia/ reperfusion and the
      inhibited effect of Rb1 on the apoptosis].

PMID- 21179830
TI  - [Changes of motor evoked potentials after spinal cord injuries in rats].
AB  - AIM: Study on the relationship between the degraded spinal cord injuries and the
      changes of the motor evoked potentials (MEP) to prove the diagnosis and prognosis
      value of MEP. METHODS: After injury at T8-T9 cord using modified Allen's weight
      drop method, 27 male SD rats were divided randomly into control group (n = 5),
      group A (50 gcf, n = 8), group B (70 gcf, n = 8) and group C (100 gcf, n = 6).
      MEPs elicited by monopolar transcortical stimulation were recorded continuously
      before injury, just after injury, 15 minutes, 1 hour, 3 hours and 6 hours after
      injury. The rate of the size of the bleeding or necrosis area to the total cord
      was also calculated. RESULTS: MEP had no significant change in the control group.
      The amplitude of MEP's early components in group A or group B decreased or even
      obliterated after SCI, and then partially recovered, while the late components
      were lost without any recovery signals. All animals in group C showed no MEP
      waves excepting 2 rats had recovery signals. The size of the cord injuries area
      increased according to the dropping force and was correlated significantly with
      the amplitude of the largest peaks of scMEP 1 hour after SCI (r = -0.821).
      CONCLUSION: The scMEP changes after SCI are correlated with the injury forces and
      the pathological changes in the cord, which indicates that scMEP can be used as
      an objective index for the cord functional monitoring.

PMID- 21179831
TI  - [Effects of D-galactose combined with lesions of nucleus basalis of Meynert on
      hippocampal long-term potentiation and synaptic morphology].
AB  - AIM: To study the changes of synaptic plasticity in rat model with Alzheimer
      disease (AD). METHODS: AD rat model was conducted by D-galactose intraperitoneal
      injection combined with lesions of nucleus basalis of Meynert (nbM). Behavioral
      performance, LTP in dentate gyrus and synaptic morphology in hippocampal CA1 were
      observed. RESULTS: (1) Escape latencies in place test in model rats were longer
      than that in control rats, and swimming time and distance between the two groups
      in platform quadrant were significant differently (P < 0.01). (2) The numerical
      density (Nu) and surface density (Su) of synaptic contact zones markedly
      decreased (P < 0.01) in model rats. (3) Augment of population spike (PS) in
      perforant path-dentate gyrus of model rats after high frequency stimulation was
      smaller than that of the control (P < 0.05). CONCLUSION: The results suggest that
      the decreased synaptic plasticity in hippocampus could responsible for the
      impairment of spatial learning of model rats.

PMID- 21179832
TI  - [The distribution of DVC on regulation of the motility of biliary system after
      microinjection of TRH].

PMID- 21179833
TI  - [Effect of losartan on arterial blood pressure and unit discharging of neurons in
      LHb and MHb of rat].
AB  - AIM AND METHODS: To investigate the effect of 2 mg/kg and 10 mg/kg losartan
      intraperitoneally (i.p) on arterial blood pressure (AP) and heart rate (HR) in
      rat and the involvement in the activity of habenulas neurons. Glass micropipette
      was used to record any changes of unit discharging of neurons in LHb and MHb
      before and after losartan was intraperitoneally injected. RESULTS: AP and HR were
      not significantly changed by 2 mg/kg losartan (i.p). However, AP was apparently
      decreased by 10 mg/kg losartan (i.p), but HR was unchanged. After 10 mg/kg
      losartan (i.p), 66.66% (12/18) unit discharging of neurons in LHb were increased
      in frequency, and 61.90% (13/21) in MHb were decreased. CONCLUSION: AP of rat was
      significantly decreased by 10 mg/kg losartan (i.p). Depressor effect of losartan
      (i.p) was involved in the excision of neurons in LHb and the inhibition in MHb.

PMID- 21179834
TI  - [Effects of hypoxic-preconditioning on anoxic-tolerance and Jun expression in
      cultured rat hippocampal neurons].
AB  - AIM: To study the effects of hypoxic preconditioning on anoxic tolerance and Jun
      expression in cultured rat hippocampal neurons after anoxia/reoxygenation.
      METHODS: 12 day cultured hippocampal neurons in control and hypoxic
      preconditioning group were exposed to anoxic environment (0.90L/L N2 + 0.10 L/L
      CO2) for 4 h, and then reoxygenated for either 24 h or 72 h. The neurons were
      immunocytochemically stained using the antiserum against Jun. The number of
      survival neurons and the percentage of Jun expressing neurons were investigated.
      RESULTS: The percentage of Jun expressing neurons induced by anoxia in hypoxic
      preconditioning group was significantly less than that in control group. The
      number of survival neurons was more in the hypoxic-preconditioning group than
      that in control group after anoxic reoxygenation. CONCLUSION: Hypoxic
      preconditioning can induce the development of anoxic-tolerance in cultured
      hippocampal neurons. The decrease in Jun expressing neurons in hippocampus may be
      an adaptive reaction to acute anoxia.

PMID- 21179835
TI  - [Effect of activity changes of Ca2+, Mg(2+)-ATPase and SDH in myocardial ischemic
      preconditioning in rats].

PMID- 21179836
TI  - [Relationship between enhanced anoxic tolerance induced by hypoxic
      preconditioning and Na+, K+ currents in cultured hypothalamic cells].
AB  - AIM: To investigate the relationship between enhanced anoxic tolerance induced by
      hypoxic preconditioning and Na+, K+ currents. METHODS: After hypoxic
      preconditioning and acute anoxia the I(Na), I(K) were measured in cultured
      hypothalamic cells by patch-clamp whole cell recording technique. RESULTS: The
      amplification of Na+ currents did not been significantly changed, but the
      amplification of K+ currents was in hypoxic preconditioning neurons; acute anoxia
      lead to the inhibition of Na+, K+ currents in the two groups, while Na+, K+
      currents in non-preconditioned control group were inhibited severity than hypoxic
      preconditioning group. CONCLUSION: It is presumed enhanced anoxia tolerance
      induced by hypoxic preconditioning may be related to the opening of K+ channels.

PMID- 21179837
TI  - [Effects of simulated high altitude hypoxia on cognitive performance].
AB  - AIM: To investigate the effects of mild and moderate hypoxia on human cognitive
      performance. METHODS: Eighteen healthy young male volunteers performed a set of
      tests of human ergonomics at sea level (300 m in Xi'an) and simulated high
      altitude of 2 800 m, 3 600 m and 4 400 m for 1 h in hypobaric chamber,
      respectively. RESULTS: The performance of continuous recognition memory tests
      compared with the controls' was deteriorated significantly (P < 0.01) after
      exposure to 2 800 m for 1 h. After exposure to 3 600 m for 1 h, in all test, the
      reaction time was much longer, the accurate rates were lower and the performance
      was worse than that of control (P < 0.05). All the parameters were deteriorated
      with the increment of altitude and the performance of all tests were much worse
      at 4 300 m for 1 h (P < 0.01). CONCLUSION: Different parameters of human
      cognitive performance may have different susceptible thresholds to hypoxia
      according to the results from our studies. The cognitive performance after
      exposure to 3 600 m for 1 h was not sufficiently effective for the demands of
      human ergonomics due to its significant deteriorating changes. However, the
      performance can be effectively restored after exposure to enough oxygen supply
      for 1 h.

PMID- 21179838
TI  - [An experimental study on the regulation of pulmonary arterial remodeling by
      protein kinase C in chronic hypoxic rats].
AB  - AIM: To investigate the effect of protein kinase C regulating pulmonary arterial
      remodeling in chronic hypoxic rats. METHODS: Electron microscope, radioactivity,
      immunohistochemistry and image analyser were used. RESULTS: (1) Mean pulmonary
      arterial pressure (mPAP) and weight ratio of RV to LV + S were significantly
      higher than that of control group (P < 0.01). (2) WA/TA and SMC were
      significantly higher than that of control group (P < 0.01). Electron microscopy
      showed the proliferation of smooth muscle cells and the disposition of
      collagenous fiber in pulmonary arterioles induced by hypoxia. (3) The total,
      cytosolic, particulate fraction PKC activity and the ratio of particulate
      fraction to total PKC activity were significantly higher than that of control
      group (P < 0.01). (4) Expression of PKC, collagen I were significantly higher
      than that of control group (P < 0.01), the difference of collagen III was not
      significant between two groups (P > 0.05). (5) There were good correlation
      between the total, particulate fraction PKC activity, the ratio of particulate
      fraction to total PKC activity, expression of PKC and SMC, collagen I in
      pulmonary arterioles. CONCLUSION: The PKC regulates the proliferation of
      pulmonary artery smooth muscle cells and expression of pulmonary arterial
      collagen in chronic hypoxic rats, which may play an important role in the
      pathogenesis of pulmonary hypertension and structural remodeling of pulmonary
      arteries.

PMID- 21179839
TI  - [Comparison of ryanodine binding to cardiac sarcoplasmic reticulum and nuclear
      envelope of rat].
AB  - AIM: The characteristics of ryanodine receptor in rat cardiac sarcoplasmic
      reticulum (SR) and nuclear envelope (NE) were studied. METHODS: Velocity and
      isopyknic gradient centrifugation was employed to fractionate rat SR and NE.
      Ryanodine receptor was assayed with [3H] ryanodine saturate binding to the
      preparations. RESULTS: The maximal binding (Bmax) and dissociating constant (Kd)
      of ryanodine receptor in rat cardiac NE were, 1.7% and 60% of those in SR
      respectively. Phosphorylation in vitro by PKA and PKC increased Bmax of the
      receptors in SR by 372% and 121%, and augmented those in NE by 221% and 306%,
      without any effects on Kd. CONCLUSION: Ryanodine receptors were present in rat
      myocardial NE, with lower density and higher affinity than those located in SR,
      which can be activated by PKA and PKC.

PMID- 21179840
TI  - [Nongenomic action of corticosterone to calcium rise induced by high-K+ in PC12
      cells].
AB  - AIM: To analyse the mechanism of corticosterone on the elevation of cytosolic
      free calcium ([Ca2+]i) induced by high-K+ in pheochromocytoma PC12 cells,
      METHODS: The [Ca2+]i was real-time checked by fluorescence image system. RESULTS:
      (1) When the cells were preincubated at 37 degrees C for 5 min in the presence of
      various concentration corticosterone and stimulated with 55 mmol/L KCl , an
      inhibitory effect of corticosterone on delta[Ca2+]i was observed in a
      concentration-dependent manner. (2) When PC12 cells were preincubated with
      various concentration of B-BSA at 37 degrees C for 5 min and stimulated with 55
      mmol/L KCl, an inhibitory effect of B-BSA on delta[Ca2+]i was observed, which is
      also concentration-dependent manner. (3) The inhibitory effect of corticosterone
      and B-BSA could not be antagonized by RU38486 at 10(-4) mol/L. (4) cycloheximide
      could not block the inhibitory effect of corticosterone after pretreating cells
      at 10(-5) mol/L at 37 degrees C for 3 hours. CONCLUSION: It is obvious that the
      locus of corticosterone action is on the plasmic membrane. The inhibitory effect
      of corticosterone is independent of protein synthesis and intracellular
      glucocorticoid receptor. The effect of corticosterone on [Ca2+]i is nongenomic
      action in PC12 cells.

PMID- 21179841
TI  - [Effects of L-arginine on the damage of myocardia induced by ischemia/reperfusion
      in rabbits].

PMID- 21179842
TI  - [Effects of mitochondrial L-arginine/nitric oxide system on mitochondrial Ca2+
      transport in rat myocardium].
AB  - AIM AND METHODS: To observe the effect of myocardial mitochondrial L-arginine (L
      Arg)/nitric oxide (NO) system on mitochondrial Ca2+ transport by using purified
      rat mitochondria and incubation of them in vitro. RESULTS: Compared with control
      group, incubation of mitochondria with L-Arg (10(-4) mol/L, NO substrate) or
      sodium nitroprusside (5 x 10(-7) mol/L, the donor of exogenous NO, SNP) increased
      significantly mitochondrial NO2- (66% and 89%, P < 0.01), respectively, and
      decreased the Ca2+ content (40% and 54%, P < 0.01). After L-Arg or SNP treatment,
      mitochondrial Ca2+ uptake were decreased by 67% and 85%, respectively (P < 0.01),
      vs control. The rate of mitochondrial Ca2+ release decreased by 11% and 8%,
      respectively (P < 0.01). When L-NAME (NO synthase inhibitor) was incubated with
      mitochondria and the L-Arg together, it inhibited the effects of L-Arg, NO2 on
      the mitochondrial NO2 formation, Ca2+ content descending, and decrease of Ca2+
      uptake and release. CONCLUSION: The data suggest that myocardial mitochondrial L
      Arg /NO systems take part in the regulation of cardiomyocytes Ca2+
      transportation.

PMID- 21179843
TI  - [Change of mitogen-activated protein kinase phosphatase-1 in heart and aorta of
      SHR and its effect on proliferation of vascular smooth muscle cells stimulated by
      angiotensin II].
AB  - AIM AND METHODS: To investigate the role of mitogen-activated protein kinase
      phosphatase-1 (MKP-1) in the regulation of cells proliferation, the expression of
      MKP-1 and extracellular signal-regulated kinase-1 (ERK-1) in heart and aorta of
      spontaneous hypertensive rat (SHR) and WKY were studied. We also investigated the
      effect of MKP-1 genes,which were transfected into vascular smooth muscle cells
      (VSMC) using the classical calcium phosphate coprecipitation technique, on the
      incorporation of 3H-TdR in VSMC stimulated by angiotensin II (Ang II). RESULTS:
      (1) Compared with that of WKY, MKP-1 expression in heart and aorta were
      significantly decreased by 53% (P < 0.01) and 45% (P < 0.01) in SHR,
      respectively. While the expression of ERK-1 in heart and aorta of SHR were higher
      than that of WKY (P < 0.01). The ratio of ERK-1/MKP-1 in heart and aorta of SHR
      were significantly higher than that of WKY. (2) 3H-TdR incorporation in VSMC
      stimulated by Ang II (10(-7) mol/L) was increased by 207% (P < 0.01), compared
      with control group. In the transfected cells with wild MKP-1 gene, Ang II-induced
      incorporation of 3H-TdR lowered 63%, compared with untransfected cells (P <
      0.05). There were no marked inhibitive role between mutant MKP-1-transfected
      cells and blank vector-transfected cells in response to Ang II, compared with Ang
      II group (P > 0.05). CONCLUSION: These results showed that the expression of ERK
      1 in heart and aorta isolated from SHR, which stimulated proliferation and
      hypertrophy of cells, is higher than that of MKP-1 which dephosphorylates and
      inactivated ERK-1. In addition, MKP-1 significantly inhibits Ang II-stimulated
      proliferation of VSMC.

PMID- 21179844
TI  - [The effects of different postoperative analgesic procedure on stress response].

PMID- 21179845
TI  - [Biomembrane damages induced by in vivo and in vitro myocardial ischemia and
      reperfusion in rats].
AB  - AIM AND METHODS: Using in vivo myocardial injury model induced by Isoproterenol
      (ISO) and the model induced by in vitro global heart ischemia/reperfusion (I/R)
      in rats, we observed the effects of myocardial ischemia and ischemia/reperfusion
      on bio-membranes of mitochondria and sarcolemma injury. RESULTS: ISO (5 mg/kg,
      s.c.) and I/R (20 min/20 min) damaged myocardial bio-membranes of rat, in which
      the lipid peroxidation of mitochondria was significantly increased, the activity
      of phospholipase A2 was activated and the contents of phospholipid and free fat
      acid were decreased and increased significantly, respectively. The membrane lipid
      fluidity and the activities of Ca(2+) -ATPase of mitochondria and Na+, K(+) 
      ATPase of sarcolemma were significantly lowered. In addition, the respiration
      function of mitochondria was declined and the oxidative phosphorylation of
      respiratory chain was uncoupled, which resulted in the decrease in the production
      of high energy phosphoric acid compounds. CONCLUSION: Myocardial injuries caused
      by ISO or I/R injured the structure and function of rat myocardial mitochondria
      and sarcolemma.

PMID- 21179846
TI  - [Relation of intramyocardial collagen remodeling to the changes of myocardial
      systolic property and angiotensin II on the overtraining rats].
AB  - AIM: To investigate the relation of intramyocardial collagen (IMC) remodeling to
      the changes of myocardial systolic property (MSP) and angiotensin II (Ang II) on
      the overtraining rats. METHODS: Morphologic remodeling of IMC and changes of
      contents of IMC and Ang II in myocardium local and circulation, and MSP in SD rat
      overtraining models were observed and determined by RM-6200 polygraph, Beckman-42
      automatic biochemistry analyser, and gamma automatic radio-immunity analyzer and
      S-570 scanning electron microscope under the conditions. RESULTS: IMC forms a
      spatial three-dimensional network structure, consisting of collagenous fiber
      connection among myocardial bundles, cardiac muscle cell group, cardiac muscle
      cells, endocardium and capillary. There are some regularities in its interlacing.
      CONCLUSION: Overtraining could lead to over hyperplasia of IMC in myocardial
      bundles, cardiac muscle cell group, cardiac muscle cell, endocardium and
      capillary, and serious injury of MLSP. The relation closes to remodeling of IMC
      and MSP and Ang II on the overtraining.

PMID- 21179847
TI  - [Current alteration of K(V) channel in SLE patient's peripheral blood lymphocytes
      and it's significant].
AB  - AIM: To observe the property alteration of K(v) channel in SLE patient's
      peripheral blood lymphocyte and its significant. METHODS: The patch-clamp
      technique was used to record the current of K(V) channel in SLE patient's
      peripheral lymphocyte. RESULTS: The current amplitude of K(V) channel in the SLE
      patient's lymphocytes decreased, it was (258.6 +/- 112.5) pA in healthy people,
      but in SLE patient it was (139.4 +/- 58.5) pA (P < 0.05). There was no other
      changes in the property of channel, include activation potential, inactivation
      property, channel closing kinetics and its pharmacological property. CONCLUSION:
      The decline of SLE patient's cell immunity may be related to the decrease of the
      amplitude of K(V) channel current.

PMID- 21179848
TI  - [Study of atria-His bundle sequential pacing on cardiac electrophysiology and
      heamodynamics in dogs].
AB  - AIM: To evaluate the effects of atria-His bundle sequential pacing on cardiac
      electrophysiology and heamodynamics in dogs. METHODS: In 20 opening chest
      anesthetized dogs, platinum electrodes were fixed at the epicardium of right
      atria (RA) and the right ventricular apex (RVA) respectively, pacing right atria
      and the right ventricle. A special lead was located at His bundle (based on a
      optical "H" wave and narrow duration of the QRS complexes recorded in ECG),
      pacing His bundle. Cardiac electrophysiology and hemodynamics parameters were
      compared in the different pacing models RA(AAI, RVA-(VVI), HisB-(VVI) single
      chamber pacing and RA-RVA(DDI), RA-HisB(DDI) dual chamber pacing. RESULTS: The
      threshold of His B pacing is similar to that of RVA pacing. Cardiac output (CO)
      is increased in pacing of RA(AAI), His B-(VVI) and RA-His B(DDI). It is increased
      by 29.64% in pacing of RA-His B(DDI) (P < 0.01) and by 0.25% (P > 0.05) in pacing
      of RA-RVA(DD1) While CO is decreased by 5.41% in RVA-VVI) pacing (P > 0.05). SV,
      LVSW and RVSW of RA-HisB(DDI) pacing are superior to those in RVA-VVI) and RA
      RVA(DDI) pacing. CONCLUSION: Right atria-His bundle sequence pacing significantly
      improves cardiac function compared with the other model pacing because it
      maintains normal physiological electronic activity sequence and systolic
      synchrony. It will be adapted to clinical application.

PMID- 21179849
TI  - [Effect and mechanism of chimonin on pulmonary hypertention of chronic hypoxia
      and hypercapnic rats].
AB  - AIM: To study the effect of chimonin on chronic hypoxia and hypercapnic pulmonary
      hypertension and to explore its mechanism. METHODS: SD rats were randomly divided
      into normal control group (A), hypoxic hypercapnic group(B), hypoxic hypercapnia
      + chimonin group (C). HO-1 and HO-1 mRNA was observed in pulmonary arterioles of
      rats by the technique of immunohistochemistry and in situ hybridization. RESULTS:
      (1) mPAP was significantly higher in rats of B group than that of A and C group.
      Differences of mCAP were not significant in three groups. (2) Blood CO
      concentration was significantly higher in rats of B group than that of A group,
      it was significantly higher in rats of C group than that of B group. (3) Light
      microscopy showed that WA/TA (vessel wall area/total area), SMC (the density of
      medial smooth muscle cell) and PAMT (the thickness of medial smooth cell layer)
      were significantly higher in rats of B group than those of A and C group. (4)
      Electron microscopy showed proliferation of medial smooth muscle cells and
      collagenous fibers of pulmonary arterioles in rats of B group, and chimonin could
      reverse the changes mentioned above. (5) HO-1 and HO-1 mRNA in pulmonary
      arterioles was significantly higher in rats of B group than that of A group, they
      were significantly higher in rats of C group than that of B group. CONCLUSION:
      Chimonin can inhibit hypoxic hypercapnia pulmonary hypertension and pulmonary
      vessel remodeling by further increasing the expression of HO-1 mRNA.

PMID- 21179850
TI  - [Studies of protective effect of SOD on damage of human RBCs stored at 4 degrees
      C].
AB  - AIM: To investigate the mechanism of protective effect of SOD (superoxide
      dismutase) on damage of RBCs stored at 4 degrees C, the studies of erythrocyte
      glucose and energy metabolism were performed. METHODS: whole blood collected from
      healthy donors and stored at 4 degrees C in ACD, GMA and SOD solutions. Before
      and post storage, some parameters were assayed. Standard methods were used for
      the in vitro tests. The 24-hour in vivo recoveries were measured by FTTC
      (Fluorescein 5-isothiocyanate) from SIGMA Company. RESULTS: All parameters of red
      blood cell glucolysis rate without oxygen condition, ATP, PK (pyruvic kinase) and
      24 h recoveries level were 86.2%, 56.4%, 64.3% and 86.2% of normal respectively
      stored in SOD solution at 4 degrees C for 75 days, distinctly more than in ACD
      and GMA groups at 75 days stored. The 24 h recovery at 75d in group SOD was near
      the recovery at 42d in group GMA. CONCLUSION: Whole blood in SOD solution can be
      stored satisfactorily for 75 days at 4 degrees C, and furnished theoretical
      evidence for RBCs survival.

PMID- 21179852
TI  - [Research on establishing a rabbit model with sudden cardiac arrest].

PMID- 21179851
TI  - [Neuropathologic investigation of area tempestas sclerosis in epileptic sensitive
      rats].
AB  - AIM AND METHODS: The relation between AT sclerosis (loss of neurons and
      proliferation of astrocytes) and long-lasting epileptic susceptibility was
      investigated by thionine staining, GFAP immunohistochemistry and observing the
      behavior of rats, after scorpion venom (SV) or normal saline (NS) administrated
      for three week. RESULTS: Compared with NS+ NS group, both the loss of neurons and
      proliferation of astrocytes were very marked in KA+ NS group (epileptic
      susceptible rats) (P < 0.05), but those changes were not visible in KA+ NS group
      (epileptic nonsusceptible rats). CONCLUSIONS: It suggested that AT sclerosis may
      be one of important reasons of the long-lasting epileptic susceptibility.

PMID- 21179853
TI  - [Expression of c-fos in various functional state of rat ovaries].
AB  - AIM AND METHODS: The method of labeled streptavidin biotin was used to study the
      expression of c-fos in various functional state of rat ovaries and its
      relationship with the levels of serum estradiol and progesterone. RESULTS: (1) In
      the mature rat, c-fos expression was found higher in interstitial gland and
      stroma of proestrous ovaries and lower in estrous ovaries, and was found higher
      in luteal cells and stroma of pregnant ovaries and lower in diestrous ovaries.
      There was a positive correlation between the area and optical density of c-fos
      expression and the levels of serum E2 and P. (2) In the immature rats, c-fos
      expression was not found in the ovaries containing preantral follicles from DES
      treated rats,and was found both in interstitial gland and stroma of the ovaries
      containing preovulatory follicles from PMSG-treated rats ,and the expression was
      higher in day 4 luteinized ovaries and lower in day 9 luteinized ovaries from
      PMSG with hCG treated rats. There also was a positive correlation between the
      area and optical density of c-fos expression and the levels of serum E2 and P.
      CONCLUSION: The results suggested in rat ovaries and might play an important role
      in follicles development, ovulation, luteum formation and regression.

PMID- 21179855
TI  - [Effects of clenbuterol on the hepatic flux of nitrogen, VFA and glucose in
      sheep].
AB  - AIM: To examine the liver mechanism with which clenbuterol (CL) is explained how
      to affect growth metabolism. METHODS: The technique of chronic poly catheter was
      used to study the effects of CL (0.8 mg/kg b w) on the hepatic flux of nitrogen,
      VFA and glucose in 4 sheep. RESULTS: The urea-nitrogen flux in CL-treated period
      always was lower than that in control during 24 h. The average flux of urea
      nitrogen in hepatic and portal vein were decreased by 16.86% (P < 0.01) and
      15.51% (P < 0.05), respectively, compared with that of control. The peptide level
      in hepatic vein was decreased with the treatment of CL, average flux of peptide
      was decreased by 38.71% (P < 0.01). But the peptide level of portal vein in CL
      treatment period was similar to control. Moreover, VFA level in the portal vein
      was enhanced by CL, the average flux of acetate in portal vein was increased by
      19.49% (P < 0.01). No difference of VFA level in hepatic vein was noted between
      CL-treated period and control. In addition, the glucose flux in hepatic vein was
      obviously increased with CL treatment, the average flux of glucose was increased
      by 25.96% (P < 0.01). And glucose flux in portal vein was also elevated during CL
      treated period. CONCLUSION: CL can affect growth metabolism of animal with
      increasing nitrogen deposition, improving absorption and utilization of VFA and
      enhancing glucose synthesis in sheep liver.

PMID- 21179856
TI  - [Insulin resistance model induced by dexamethasone in rats].
AB  - AIM: To build a easy and reliable rat model of insulin resistance. METHODS:
      Changes concerning sugar metabolism were observed in experimental rats injected
      intraperitoneally by different doses of dexamethasone. RESULTS: The changes by
      dexamethasone in fasting blood insulin and insulin resistance prior to that of
      fasting blood glucose were dose and time dependent. CONCLUSION: It was
      convenience to set up a insulin resistance model induced by dexamethasone in rats
      which would favor other related research.

PMID- 21179858
TI  - [Delayed rectifier K+ channel in neuron of rat cerebral cortex].

PMID- 21179859
TI  - [Sedation therapy which shortens life--homicide or adequate treatment?].

PMID- 21179860
TI  - [Whether compulsory measures are per definition always a deviation that should be
      analyzed: "We want to continue the dialogue"].

PMID- 21179861
TI  - [Homocysteine can contribute with another piece to the dementia puzzle. Vitamin B
      supplementation seems to reduce the progression of brain atrophy].

PMID- 21179862
TI  - [Diabetes type 2. Better prevention and treatment in sight].

PMID- 21179863
TI  - [The interplay between environment and genetics determines who gets diabetes].

PMID- 21179864
TI  - [Comeback for the beta cells in the pathogenesis of diabetes].

PMID- 21179865
TI  - [Molecular mechanisms underlying insulin resistance in skeletal muscle].

PMID- 21179866
TI  - [Diet in diabetes--strong opinions but poor knowledge].

PMID- 21179867
TI  - [Tough glucose reduction necessary in newly diagnosed diabetes].

PMID- 21179868
TI  - [Intensive efforts for future antidiabetic agents].

PMID- 21179869
TI  - [Guidelines for care of young people with anxiety and depression should be
      revised].

PMID- 21179870
TI  - [We need fairer measures of hospital physicians' work with the patients].

PMID- 21179871
TI  - [Biosimilars attack...].

PMID- 21179872
TI  - [A vermiform appendix beneficial for the human being].

PMID- 21179873
TI  - [Children from skin cells--a future alternative to surrogate motherhood?].

PMID- 21179874
TI  - [Increased number of multimorbidity patients put demands on health care].

PMID- 21179875
TI  - [Frail aging and multimorbidity affect more and more. Focus must be moved from
      isolated diseases to complex health problems].

PMID- 21179876
TI  - [Treatment of sleep disorders in adults. Summary of a systematic literature
      review from SBU].

PMID- 21179877
TI  - [Tonsillitis in young people--consider Fusobacterium necrophorum].

PMID- 21179878
TI  - [Clinical eye for blue-coloured ears lead to the correct diagnosis:
      alkaptonuria].

PMID- 21179879
TI  - [Heart arrest in our fathers' tracks. Three successfully treated cases during the
      Vasa Ski Race 2010].

PMID- 21179880
TI  - [Safer drug administration with computerized drug records. Solution for many of
      the old-time problems--but new risks appear].

PMID- 21179881
TI  - [Health services of today benefit from increased patient centered care. Focus on
      the patient yields effective care--but there is also room for paternalism].

PMID- 21179882
TI  - [The backside of success: Late adverse effects of radiotherapy in Hodgkin
      lymphoma].

PMID- 21179883
TI  - [Reduce VAT for bicycles and pay newly diagnosed diabetics to keep themselves
      healthy. Obesity strategies downunder].

PMID- 21179884
TI  - [Alternative Nobel Prize to Israeli medical association].

PMID- 21179885
TI  - [Ethics police or appeal to ethical reflection?].

PMID- 21179886
TI  - [Swedish hospital in Korea--humanitarian aid in the war].

PMID- 21179887
TI  - A non-invasive method based on saliva to characterize transthyretin in familial
      amyloidotic polyneuropathy patients using FT-ICR high-resolution MS.
AB  - PURPOSE: To identify, characterize and perform a relative quantification of human
      transthyretin (TTR) variants in human saliva. EXPERIMENTAL DESIGN: Serum and
      saliva samples were collected from healthy and familial amyloidotic
      polyneuropathy (FAP) patients, proteins separated by SDS-PAGE, TTR bands excised,
      in-gel digested and analyzed by MALDI-FTICR. RESULTS: We identified and performed
      a relative quantification of mutated and native TTR forms in human saliva, based
      on FTICR-MS. The results are quantitatively identical to the ones obtained with
      human serum. In FAP patients subjected to cadaveric liver transplant, the TTR
      mutant form is no longer detected in saliva, while in patients receiving a domino
      liver from a FAP donor the mutant form of TTR becomes detectable in saliva, thus
      demonstrating the serum origin of TTR in saliva. CONCLUSIONS AND CLINICAL
      RELEVANCE: Saliva TTR originates in serum and the ratio of mutant to native TTR
      is preserved. The method provides a non-invasive detection of mutated TTR and a
      relative quantification of TTR forms. Diagnostic and disease prognosis of FAP is
      crucial at early stages of the disease and after liver transplantation, the only
      curative therapy. A suitable non-invasive method was developed for monitoring the
      most important FAP biomarker in human saliva.

PMID- 21179888
TI  - Optimization protocol for amyloid-beta peptides detection in human cerebrospinal
      fluid using SELDI TOF MS.
AB  - PURPOSE: The aim of the present work was to set up an optimized protocol for
      human cerebrospinal fluid amyloid-beta (Abeta) profiling. EXPERIMENTAL DESIGN: We
      devised an immunoproteomic assay that employs monoclonal antibodies (mAbs) on
      Preactivated Surface (PS20) chip array followed by SELDI TOF MS. A comparison of
      a number of factors was performed, and the impact of these differences was noted.
      Each variable was tested using in parallel two different mAbs, 6E10 and 4G8. In
      addition, we tested whether the combined use of these two mAbs could improve the
      capture of N and C-terminally truncated Abeta peptides and then the quality of
      spectra. RESULTS: The best results were obtained using a mixture of Abeta mAbs
      (0.125 MUg/MUL 6E10+4G8): 15 Abeta peptides (including 3 N-terminally truncated
      forms) were detected. CONCLUSIONS AND CLINICAL RELEVANCE: This approach has many
      potential advantages in speed, sensitivity and economy of reagents and could be
      helpful in order to define the role played by specific Abeta truncated forms in
      cognitive decline.

PMID- 21179889
TI  - Report from the Wellcome Trust/EBA "Perspectives in Clinical Proteomics" retreat-
      a strategy to implement next-generation proteomic analyses to the clinic for
      patient benefit: pathway to translation.
AB  - Proteomics has long been thought to hold the promise of producing results of
      clinical utility which will influence patient treatment and outcomes. A recent
      Wellcome Trust/EBI meeting and retreat--"Perspectives in Clinical Proteomics"-
      brought together experts from a broad range of stakeholder groups with an
      interest in ensuring proteomics achieves this aim. This viewpoint presents views
      derived from these forums, proposing a pathway for the development of next
      generation proteomic analyses in the clinical setting from selection of
      candidates through to their validation and ultimate demonstration of utility
      through health technology assessments. Although not meant to be all encompassing,
      important elements for proteomics researchers to consider are presented.

PMID- 21179890
TI  - Basic and clinical proteomics from the EU Health Research perspective.
AB  - The European Union (EU) is one of the main public funders of research in Europe
      and its major instrument for funding is the Seventh Framework Programme for
      research and technological development (FP7). The bulk of funding in FP7 goes to
      collaborative research, with the objective of establishing excellent research
      projects and networks. Understanding the functions of proteins is essential for
      the rational development of disease prevention, diagnosis and treatment,
      therefore the EU has largely invested in proteomics, in particular for technology
      development, data standardisation and sharing efforts, and the application of
      proteomics in the clinic. The scientific community, including both academia and
      industry, is encouraged to apply for FP7 funding so that the EU can even more
      efficiently support innovative health research and ultimately, bring better
      healthcare to patients.

PMID- 21179891
TI  - Biomarkers as disease definition: mantle cell lymphoma as an example.
AB  - The introduction in pathology practice of a new biomarker that is contributing to
      define a disease requires a series of investigations. Now that new biomarkers are
      being discovered continuously it is important to learn from successful examples
      of markers that are presently widely used. In this historical account the steps
      are described that have led to the use of immunohistochemical staining of tissue
      samples with an antibody against cyclinD1 to diagnose mantle cell lymphoma.
      Furthermore, a short outlook is given on the introduction of proteomics as a tool
      in the diagnosis of lymphoma and the potential route to be taken for introducing
      this technology into clinical practice.

PMID- 21179893
TI  - Veterinary students raise AIDS awareness.

PMID- 21179892
TI  - Hemoglobin depletion from plasma: considerations for proteomic discovery in
      sickle cell disease and other hemolytic processes.
AB  - PURPOSE: Hemoglobin (Hb) depletion with nickel affinity chromatography has been
      shown to increase the number of proteins identified in proteomic studies of
      erythrocytes, but limited data exist on the application of this technique in
      depletion of Hb from plasma or serum required for clinical biomarker studies. The
      aim of this study was to explore the potential of using nickel-beads for Hb
      depletion of plasma. EXPERIMENTAL DESIGN: Nickel-nitrilotriacetic acid (Ni-NTA)
      affinity chromatography was used to deplete Hb from hemolyzed plasma samples
      obtained from children with sickle cell disease (SCD, n=7) and normal human
      plasma (n=4). Ni-NTA-bound proteins were analyzed by one-dimensional GE, followed
      by in-gel digestion for characterization using an LTQ-Orbitrap hybrid mass
      spectrometer. In addition, the loss of two non-Hb-related plasma proteins,
      thrombospondin1 and L-selectin, by Ni-NTA was determined by ELISA (SCD n=6, non
      SCD controls n=2). RESULTS: Ni-NTA resulted in an average 60% decrease in plasma
      protein concentration, which was not hemolysis dependent. Specifically, Hb (7
      peptides) and the top three proteins, -2-macroglobulin (75 peptides),
      apolipoprotein B-100 (73 peptides), and albumin (42 peptides) were Ni-NTA bound.
      In addition, using an ELISA assay two non-Hb-associated plasma proteins
      thrombospondin1 and L-selectin were decreased by Ni-NTA. CONCLUSIONS AND CLINICAL
      RELEVANCE: Hb depletion with Ni-NTA is effective for Hb removal but is not
      specific. There is a potential for deleterious depletion of potential biomarkers
      that may limit the applicability of this method. Consideration of alternate
      methods of Hb depletion for clinical proteomics may be warranted.

PMID- 21179894
TI  - Appellate court gives mixed ruling on Ohio rBST labeling rules. Judges strike,
      uphold aspects of dairy labeling regulations.

PMID- 21179895
TI  - Catholic action and the development of the Irish welfare state in the 1930s and
      1940s.

PMID- 21179896
TI  - Bhutan: from the Mediaeval to the millennium.

PMID- 21179897
TI  - [Wolff's empirical psychology and Kant's pragmatic anthropology: the beginnings
      of anthropology in the 18th century].

PMID- 21179898
TI  - [Status quo of malaria occurrence].

PMID- 21179899
TI  - [Strategy for prevention of infectious complications during surgery at a cancer
      hospital].

PMID- 21179900
TI  - [Clinical rationale for using dabigatran etexilate in the complex treatment of
      venous thromboembolism].

PMID- 21179901
TI  - [Effect of infusion hepatoprotectors on hepatic function in experimental
      cholestasis].

PMID- 21179902
TI  - [Aortic coarctation in newborn].

PMID- 21179903
TI  - [Treatment tactics by small lung tumors].

PMID- 21179904
TI  - The Third International Congress on Physical Activity and Public Health: Toronto,
      May 5-8, 2010.

PMID- 21179906
TI  - To customise or not to customise: that is the question.

PMID- 21179907
TI  - Addressing loneliness in a retirement village community: a pilot test of a print
      delivered intervention.
AB  - AIM: To explore perceptions of a self-help print-delivered intervention aimed at
      encouraging social well-being and addressing loneliness in a retirement village
      community. METHOD: A total of 58 residents of an Australian retirement village
      received a series of five factsheets addressing various dimensions of loneliness.
      RESULTS: The factsheets raised awareness of the importance of social well-being
      and loneliness. However, the approach was considered difficult to update and was
      not appropriate for those from a non-English speaking background or with vision
      impairments. The non-face-to-face approach also was unable to address issues of
      loneliness associated with bereavement. CONCLUSION: This form of intervention
      offers a cost-effective way to raise awareness of loneliness and social well
      being in a retirement village community when issues of updating and presentation
      of information are taken into consideration.

PMID- 21179908
TI  - No recurrence in otoplasty: is that possible?
AB  - INTRODUCTION: Otoplasty or correction of prominent ears, is one of most commonly
      performed surgeries in plastic surgery both in children and adults. Until
      nowadays, there have been more than 150 techniques described, but all with
      certain percentage of recurrence which varies from just a few up to 24.4%.
      OBJECTIVE: The authors present an otoplasty technique, a combination of
      Mustarde's original procedure with other techniques, which they have been using
      successfully in their everyday surgical practice for the last 9 years. The
      technique is based on posterior antihelical and conchal approach. METHODS: The
      study included 102 patients (60 males and 42 females) operated on between 1999
      and 2008. The age varied between 6 and 49 years. Each procedure was tailored to
      the aberrant anatomy which was analysed after examination. Indications and the
      operative procedure are described in step-by-step detail accompanied by drawings
      and photos taken during the surgery. RESULTS: All patients had bilateral ear
      deformity. In all cases was performed a posterior antihelical approach. The
      conchal reduction was done only when necessary and also through the same
      incision. The follow-up was from 1 to 5 years. There were no recurrent cases. A
      few minor complications were presented. Postoperative care, complications and
      advantages compared to other techniques are discussed extensively. CONCLUSION:
      All patients showed a high satisfaction rate with the final result and there was
      no necessity for further surgeries. The technique described in this paper is easy
      to reproduce even for young surgeons.

PMID- 21179909
TI  - Relationship between sociodemographic, anthropometric and biochemical
      characteristics and degree of peripheral arterial disease.
AB  - INTRODUCTION: Peripheral arterial disease (PAD) is a severe atherosclerotic
      condition. The relationship between various risk factors and severity of PAD,
      measured by Ankle Brachial Index (ABI), has been the subject of a relatively
      small number of studies. OBJECTIVE: The aim of the present study was to
      investigate whether there was any relationship between severity of PAD, expressed
      as ABI, and anthropometric, clinical and biochemical characteristics of patients,
      including inflammatory markers. METHODS: The cross-sectional study, involving 388
      consecutive patients with verified PAD, was performed at the Dedinje Vascular
      Surgery Clinic in Belgrade. The diagnosis of PAD was defined by Doppler
      sonography as ABI < 0.9, and by symptoms. Data on cardiovascular risk factors,
      anthropometric parameters, clinical and biochemical characteristics were
      collected for all participants. In the analysis, chi2 test, t-test and
      multivariate logistic regressions were used. RESULTS: According to the results of
      multivariate analysis (the model of which included age, percentage of body fat,
      average value of uric acid, high sensitivity C-reactive protein--hsCRP > or = 3
      mg/L, fibrinogen > or = 4 g/L, Baecke index of physical activity at work and
      Baecke index of leisure-time physical activity), the patients with more severe
      form of peripheral arterial disease (ABI < or = 0.40) had more frequently
      increased high sensitivity C-reactive protein (p = 0.002), lower Baecke index of
      physical activity at work (p = 0.050) and lower Baecke index of leisure-time
      physical activity (p = 0.024). Average value of body fat was significantly higher
      in the patients with a less severe form of disease (p = 0.006). CONCLUSION:
      According to the results obtained, the increased values of hsCRP and physical
      inactivity are associated with a more severe form of PAD (ABI < or = 0.40).

PMID- 21179910
TI  - Preoperative administration of cephalosporins for elective caesarean delivery.
AB  - INTRODUCTION: Antibiotic prophylaxis means administration of antibiotics in
      prevention of infections. OBJECTIVE: To investigate the efficacy of a single dose
      preoperative administration of ceftriaxone and cefazolin in the prevention of
      intra- and postoperative infections in the parturients without high risk of
      inflammation. METHODS: The first group of 45 pregnant and 4 non-pregnant women
      were preoperatively administered ceftriaxone in a dose of 2 g, i.v., 10 minutes
      before the planned surgery. The second group of 45 pregnant and 4 non-pregnant
      women were preoperatively administered cefazolin in a dose of 2 g i.v., 10
      minutes before the planned surgery. The concentrations of antibiotics were
      estimated immediately and 6 hours following the operation, as well as in the
      amniotic fluid and umbilical cord in the group of pregnant women. The estimation
      of antibiotic concentration was done by the method of liquid chromatography.
      RESULTS: The mean concentrations of antibiotics in the patients following the
      elective caesarean section were as follows: ceftriaxone--22.7 microg/I. vs
      cefazolin--44.8 microg/l. Six hours later, the concentration of antibiotic
      decreased, but the concentration of cefazolin was still over the MIC for
      sensitive bacteria. The mean concentrations of antibiotics following
      gynaecological surgery in the non-pregnant patients were as follows: ceftriaxone-
      12.0 microg/I vs cefazolin--30.1 microg/l. Six hours later, the concentration of
      antibiotic decreased. CONCLUSION: It is most optimal to administer a single-dose
      of the first generation cephalosporins -cefazolin- immediately following the
      clamping of the umbilical cord as well as in preoperative prophylaxis in
      gynaecological operations.

PMID- 21179911
TI  - Analysis of salt content in meals in kindergarten facilities in Novi Sad.
AB  - INTRODUCTION: Investigations have brought evidence that salt intake is positively
      related to systolic blood pressure and that children with higher blood pressure
      are more susceptible to hypertension in adulthood. In developed countries the
      main source of salt is processed food. OBJECTIVE: The aim of this paper was to
      determine total sodium chloride (NaCl) in average daily meal (breakfast, snack
      and dinner) and in each of three meals children receive in kindergarten. METHODS:
      From kindergarten, in the meal time, 88 samples of daily meals (breakfast, snacks
      and dinner) offered to children aged 4-6 years were taken. Standardized
      laboratory methods were applied to determine proteins, fats, ash and water in
      order to calculate energy value of meal. The titrimetric method with AgNO3, and
      K2CrO4 as indicator, was applied in order to determine chloride ion. Content of
      NaCl was calculated as %NaCl = mlAgNO3 x 0.05844 x 5 x 100/g tested portion. NaCl
      content in total daily meal and each meal and in 100 kcal of each meal was
      calculated using descriptive statistical method. Student's t-test was applied to
      determine statistical differences of NaCl amount among meals. RESULTS: NaCl
      content in average daily meal was 5.2 +/- 1.7 g (CV 31.7%), in breakfast 1.5 +/-
      0.6 g (CV 37.5%), in dinner 3.5 +/- 1.6 g (CV 46.1%) and in snack 0.3 +/- 0.4 g
      (CV 163.3%). NaCl content per 100 kcal of breakfast was 0.4 +/- 0.1 g (CV 29.5%),
      dinner 0.7 +/- 0.2 g (CV 27.8%) and snack 0.13 +/- 0.19 g (CV 145.8%). The
      difference of NaCl content among meals was statistically significant (p < 0.01).
      CONCLUSION: Children in kindergarten, through three meals, received NaCl in a
      quantity that exceeded internationally established population nutrient goal for
      daily salt intake. The main source of NaCl was dinner, a meal that is cooked at
      place.

PMID- 21179912
TI  - Rehabilitation in diabetic patients.
AB  - Physical activity is very important for diabetic patients. In normal subjects
      physical activity postpones diabetes mellitus and in diabetic patients postpones
      the cardiovascular complications. In diabetic patients with cardiovascular
      disease, physical training increases exercise capacity, decreases complications
      and prolongs survival. Physical activity can be applied in diabetic patients as
      physical activity counseling or physical training, the second being recommended
      to be ambulatory and supervised but, sometimes, also home rehabilitation can be
      useful. Aerobic exercises, but also resistance exercises will be applied for a 30
      60 min duration at least 3x/ week, recommended 5x/ week, and optimal every day.
      Some specific aspects of diabetic patients as hyper or hypoglycemia, autonomic or
      peripheral neuropathy, retinopathy, have to be considered during physical
      rehabilitation and sometimes physical training has to be modulated according to
      them. In conclusion, physical activity and training represent a real chance for
      every diabetic patient and has to be recommended and applied in all of them.

PMID- 21179913
TI  - Calcific aortic valve disease and aortic atherosclerosis--two faces of the same
      disease?
AB  - Calcific (degenerative) aortic valve disease is the most common etiology of
      acquired aortic valve stenosis. Historically, it was seen as a degenerative,
      "senile-like" process, resulting from aging--"wearing and tearing"--of the aortic
      valve. However, several lines of evidence suggest that calcific valve disease is
      not simply due to age-related degeneration but, rather, it is an active disease
      process with identifiable initiating factors, clinical and genetic risk factors,
      and cellular and molecular pathways that mediate disease progression.
      Histopathologically, the early lesions of aortic valve sclerosis resemble
      arterial atherosclerotic plaques. Furthermore, atherosclerotic risk factors and
      clinical atherosclerotic cardiovascular disease are independently associated with
      aortic sclerosis suggesting that it represents an atherosclerosis-like process
      involving the aortic valve. Until now, the only established treatment for
      symptomatic aortic valve stenosis has been valve replacement. Newer therapies
      that may modify or reduce the likelihood of developing aortic valve disease are
      highly desirable and are currently under investigation. In this article we tried
      to review the available data on calcific aortic valve disease, starting from
      histological and pathogenic aspects and finishing with therapeutic implications,
      in order to characterize its relationship with the atherosclerotic process.

PMID- 21179914
TI  - Liver biopsy versus noninvasive methods--fibroscan and fibrotest in the diagnosis
      of non-alcoholic fatty liver disease: a review of the literature.
AB  - The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing in
      general population so it is impossible to perform liver biopsy in such a large
      number of patients to identify those with advanced fibrosis or non-alcoholic
      steatohepatitis. Liver biopsy has a potential sampling error, it is invasive and
      prone to complications, so it is no longer considered as mandatory as first line
      screening tools for chronic liver disease. The development of non-invasive
      biomarkers, FibroTest-ActiTest in 2001 and more recently FibroMax, as well as
      transient elastography (TE) has changed the management of chronic liver disease.
      The aim of this review is to summarize the advantages and limits of the available
      non-invasive biomarkers of liver fibrosis, in comparison with liver biopsy in
      NAFLD patients.

PMID- 21179915
TI  - Helicobacter pylori: pathological mechanism involved in gastric colonization.
AB  - Since 1982, when Marshall and Warren highlighted the presence of H. pylori at the
      apical pole of the epithelial gastric cells, the medical literature has
      registered a cascade of subsequent researches concerning this amazing bacterium,
      its action on the human body and the body response. The apogee of these studies
      and conclusions about the pathogenic role of HP was touched with its certain
      recognition as class one carcinogenic agent (Peura 1997, WHO), becoming the first
      bacteria with such an action. The data gathered in the last period identify
      different virulence factors of HP, but fail to fully explain the relatively low
      incidence of gastric cancer in HP carriers; therefore, it is now considered that
      the carcinogenic potential related to HP infection in humans is due to the
      synergic and complementary association of the bacterial genetic equipment with
      diet and host response.

PMID- 21179916
TI  - Peptic upper gastrointestinal bleeding: diagnosis and treatment. A monocentric
      experience on a 5 years period.
AB  - AIM: We evaluated all the cases of upper gastrointestinal hemorrhages admitted in
      the Department of Endoscopy of our Clinic during a 5 years period. MATERIAL AND
      METHOD: 810 patients were included in our study, 64.3% males and 36.7% females,
      mean age 58.7 +/- 15.2 years (17-96 years). The main cause of the upper digestive
      hemorrhage was peptic ulcer (82.6%), equally divided in gastric and duodenal. All
      the ulcers were assessed according to the Forrest classification. RESULTS:
      Endoscopic haemostasis was performed in 40% of all cases, only epinephrine
      injection (1/10,000) in 44.4% of cases; combined therapy (injection + clip or
      thermocoagulation) in 40.3% of the cases and clip or thermocoagulation alone in
      15.3% of the cases. A marked reduction of haemostasis using epinephrine injection
      alone (as monotherapy) was observed during the period of study. Postendoscopic
      treatment rebleeding occurred in 19.8% of cases; 3.6% of the patients have had a
      fatal outcome and surgical treatment was needed in 2.7% of cases. CONCLUSION: In
      an experienced Department of Endoscopy, the majority of upper gastrointestinal
      hemorrhages can be endoscopically treated with good results. In the last years,
      endoscopical haemostatic bitherapy (adrenaline injection+clipping or bipolar
      coagulation) replaced injection of adrenaline like monotherapy for ulcer
      hemostasis.

PMID- 21179917
TI  - Bedtime versus at awakening administration of BP lowering drugs--is it the way to
      success?
AB  - The "manometric" way of considering the complex management of high blood pressure
      (HBP) must remain ancient history. The huge therapeutical armamentarium existing
      nowadays allows us to select the drug/s most appropriate for the
      comorbidities/particularities of each case. The BP level target, unanimously
      considered a very important element of HBP management, must not be the only one.
      The so-called pleiotropic effects of the different classes of antihypertensive
      drugs must always influence our way of thinking. Another important possibility to
      improve the therapeutical efficacy of the antihypertensive treatment is
      chronotherapy. The aim of the present study is to demonstrate the possibility of
      some benefic effects by imposing, by chronotherapy, a "normal" "dipping" status
      of the BP values. Among the surrogate end-points that can be used to demonstrate
      the benefits of this kind of HBP management we chose the structural and
      functional cardiac parameters, echocardiographically determined--using the
      criteria of the American Society of Echocardiography. We studied the evolution of
      these parameters of the left ventricle (LV) and we have evaluated them after 3
      months of once-a-day morning (at awakening) administration, and respectively
      after 3 months of once-a-day administration in the evening (at bedtime) of:
      Prestarium (perindopril) cp 10 mg Tarka (cp 180 mg verapamil hydrochloride/2 mg
      trandolapril) Norvasc (amlodipine besilat) cp 10 mg as monotherapy, in 60
      patients. We studied the anatomical parameters of the left ventricle (dimensions
      measured enddiastolically: the thickness of the interventricular septum, the
      thickness of the posterior wall, the internal diameter of the LV), the LV mass
      (which has a cutedge value for hypertrophy of the LV-LVH--of 134 g/m2 for men and
      110 g/m2 for women) and the functional parameters, systolic as diastolic of the
      LV. We noticed a statistically significant reduction (p < 0.05) in all the 3
      subgroups, of the functional parameters, these ones becoming similar to those in
      normotensive subjects only after the evening (at bedtime) administration of the
      studied drugs. The differences between the 3 subgroups for all the studied
      parameters, also in comparison with the normotensive subjects, have not been
      statistically significant after vesperal (at bedtime) administration of the
      studied drugs. It is, thus, possible that by an optimal treatment,
      chronotherapeutically "tailored", to obtain a normalisation of the anatomical and
      functional parameters of the LV and a significant improvement of the prognosis of
      these patients.

PMID- 21179918
TI  - The prevalence of peripheral arterial disease in relationship with cardiovascular
      risk factors in Romania.
AB  - Peripheral arterial disease (PAD) represents a disease with high prevalence and
      related mortality and morbidity. However, there are spearing epidemiological
      information regarding PAD in Romania. The objective of our study was to evaluate
      the prevalence of PAD in relationship with cardiovascular risk factors (RF) in
      Romania. MATERIAL AND METHODS: In the study we randomly enrolled a number of 796
      patients aged over 40 from those persons presenting during a 3 month period at
      the warding rooms in The Emergency Hospital in Bucharest. For every patient a
      questionnaire was completed containing demographical data, information about
      personal RF and history of atherothrombotic cardio-vascular disease and also
      information about patient's treatment. For each patient the height, the weight,
      waist circumference and ankle-brachial index (ABI) have been measured. RESULTS:
      The prevalence of PAD was 18.7%, 79.19% from patients being newly diagnosed.
      Multivascular atherothrombotic disease was noted in 16.1% of PAD patients. FR
      related with the presence of PAD were age, diabetes mellitus (DM), smoking and
      former coronary disease. Smoking and DM represented the most unfavourable risk
      factors association in respect with PAD. CONCLUSIONS: We found a high prevalence
      of PAD but comparable with that one reported in other European countries. The
      majority of the patients were newly diagnosed. The RF most frequented encountered
      have been DM and smoking, their association conducing to further increase in risk
      of having PAD. We appreciate the necessity of active identification of PAD by
      means of ABI measurement in patients with RF or other cardiovascular disease.

PMID- 21179919
TI  - Risk profile in women with acute myocardial infarction.
AB  - The studies in the literature of the past years have noticed the particular
      characteristics of the ischemic heart disease in women, who seem to be lacking
      early diagnosis and invasive treatment of coronary heart disease. They especially
      emphasize that the evolution, complications and mortality in myocardial
      infarction in women are more severe. THE GOAL OF THE STUDY: The evaluation of
      clinical, investigational and therapeutic aspects in a lot of women with acute
      myocardial infarction (AMI) versus a lot of men with the same pathology,
      hospitalised in the same period. MATERIAL AND METHODS: 78 women hospitalised in
      the Emergency Institute of Cardiovascular Diseases between 1st January 1999 and
      30th October 2001 with acute myocardial infarction. 109 men hospitalised in the
      Emergency Institute of Cardiovascular Diseases with acute myocardial infarction
      in the same period. INCLUSION CRITERIA: acute myocardial infarction, coronary
      angiography +/=left ventriculography. The lot of study and the witness lot were
      divided into 3 subgroups based on the severity of coronary lesions: Group I: left
      main stenoses, Group II: stenoses >60% on the other epicardial coronary vessels,
      Group III: stenoses <60% on the other epicardial coronary vessels. The risk
      factors, clinical data, cardiac performance indices and medical and invasive
      treatment were compared between the two groups. RESULTS/CONCLUSIONS: The women
      hospitalised with AMI were older than men, had more diabetes and hypertension as
      main risk factors than men, with the exception of smoking, had more frequent
      heart failure and diastolic dysfunction of left ventricle. The favorite invasive
      treatment in women was the angioplasty with application of stent and in men-
      coronary bypass.

PMID- 21179920
TI  - Are systemic inflammatory profiles different in patients with COPD and metabolic
      syndrome as compared to those with COPD alone?
AB  - BACKGROUND: Metabolic Syndrome (MS) is frequent in patients with COPD, almost 50%
      of patients with COPD had one or more components of metabolic syndrome (MS).
      Moreover, it was demonstrated that BMI might be one of the determinants of COPD
      phenotype. Chronic comorbid diseases affect health outcomes in COPD, in fact,
      patients with COPD mainly die of non-respiratory disorders such as cardiovascular
      disease. Inflammation plays a key role in COPD and MS but we do not know the real
      inflammatory profile of these patients. A better understanding of the origin and
      consequences of systemic and local inflammation, and of potential therapies, will
      most likely lead to better care of patients with COPD. METHODS: We compared 64
      consecutive, consenting smoker patients with COPD and MS (mean age: 62.7 +/- 0.7
      years) with this serum inflammatory profile (hsCRP: 1.9 +/- 0.01 mg/dL, TNF
      alpha: 6,4 +/- 0.1 pg/mL, adiponectin: 4.7 +/- 0.01 mg/L) versus 69 COPD smoker
      patients matched for age (mean age 61.4 +/- 0.4 years) with following serum
      inflammatory cytokine (CRP: 0.9 +/- 0.01 mg/dL, TNF-alpha: 3.9 pg/mL +/- 0.01,
      adiponectin: 9.3 +/- 0.01 mg/L). COPD and MS was diagnosed according to the GOLD
      criteria respectively IFD 2005 criteria. Data were expressed as mean +/- SE
      (standard error). Comparisons of parameters among the two groups were made by
      Student unpaired t test. The level of statistical significance was set as p <
      0.05. RESULTS: Serum TNF-alpha and high-sensitivity CRP levels in patients with
      COPD and MS were significantly higher (p < 0.05) than those of COPD alone. Plasma
      adiponectin levels in patients with COPD were significantly higher (p < 0.05)
      than in subjects with COPD and MS. CONCLUSIONS: Patients with COPD and MS have a
      more exacerbated systemic inflammatory profile and a significantly reduced
      specific adipose response represented by adiponectin than patients with COPD
      alone. These results help us to better understand the inflammatory pattern in
      patients with COPD with metabolic disorders and permit us to sustain the
      regulatory role of adiponectin in metabolism balance. It is possible that this
      association between COPD and MS with a specific inflammatory pattern (high serum
      levels of CRP and TNF-a but with low plasma levels of adiponectin) to explain the
      high rate of death adjudicated as due to cardiovascular causes.

PMID- 21179921
TI  - The prognosis of glycoregulation disturbances and insulin secretion in alcoholic
      and C virus liver cirrhosis.
AB  - We studied 49 alcoholic and viral C liver cirrhosis, over a period of 5 years, we
      evaluated OGTT, HOMA-IR, HOMA-beta, child score, diabetes mellitus and liver
      cirrhosis complications and survival. Both insulin resistance and lower insulin
      secretion in liver cirrhosis are important determinants of the degree of oral
      glucose tolerance. There is a correlation between the bad prognosis in patients
      with cirrhosis and glycoregulation disturbances, especially in those with
      alcoholic etiology.

PMID- 21179922
TI  - Expression of IL-6 activity in patients with acute ischemic stroke.
AB  - Cerebral ischemia initiates an inflammatory response in the brain and periphery.
      Inflammatory mechanisms, including IL-6, are suspected to play a role in arterial
      thrombogenesis. Their presence in the periphery is still controversial. The
      question arises as to whether IL-6 might directly contribute to cerebral infarct
      pathogenesis. IL-6 has several pro-inflammatory effects which may contribute to
      the induction and evolution of early inflammatory injury in the brain and its
      vasculature. The objective of this study was to test the hypothesis that there is
      a relationship between inflammation and the ischemic stroke measuring the levels
      of IL-6 in the blood of acute ischemic stroke patients. Plasma IL-6 was measured
      in 46 patients in the first 24 hours after acute ischemic stroke and in 98
      controls matched for sex and age. Forty-five out of 46 acute ischemic stroke
      patients presented high IL-6 values. Fourteen out of 98 controls presented IL-6
      values higher than normal. Mean level of circulating IL-6 was in acute ischemic
      stroke patients 26.5 +/- 2.3 pg/mL (range 6.4-161.3 pg/mL), significantly higher
      as compared to that in controls 3.9 +/- 1.5 pg/mL (range 2.3-5.9 pg/mL) [p <
      0.0001, 95% CI (9.186 to 457.53)]. In our study, IL-6 levels were significantly
      elevated in the first 24 hours after ischemic stroke. This observation supports
      the hypothesis that IL-6 production is an inflammatory response to acute hypoxic
      ischemic injury. IL-6 may serve as warning sign, because it increases early in
      inflammation.

PMID- 21179923
TI  - Risk factors for diabetic nephropathy: intrinsic or extrinsic renal?
AB  - Diabetic nephropathy (DN) is the result of numerous risk factors, such as
      hyperglycaemia, several genetic polymorphisms, offering susceptibility or
      individual resistance to DN. There are numerous, well-studied risk factors for
      DN, the majority being renal extrinsic, but there have been identified and
      studied renal intrinsic factors (the number of glomeruli, the volume of
      glomeruli) which can be structural determinants of the risk for the development
      of DN and may be precocious markers of DN. The clarification of the role of
      genetic factors in the pathogeny of DN may contribute to the evaluation of DN
      risk, allowing the selection of patients eligible to new precocious therapies
      (primary prevention) and the prevention of ESRD (secondary prevention).

PMID- 21179924
TI  - Cardiovascular autonomic neuropathy in diabetes mellitus.
AB  - Diabetes mellitus (DM) is a disease of modem world, with a great impact on the
      life of the affected individual. Autonomic neuropathy (AN), also called visceral
      neuropathy, is a disease of the autonomic nervous system affecting mostly the
      internal organs. The diagnosis of AN can be made in early stages, and is called
      sub-clinical neuropathy. Cardiovascular autonomic neuropathy (CAN) correlates
      with a lot of signs and symptoms, which are more or less specific. CAN is
      associated with poor prognosis and may result in severe symptomatic diseases, but
      it is also associated with silent ischemia. In conclusion, CAN is a very
      important complication of both type 1 and type 2 diabetes which can be early
      diagnosed by some specific test and should be taken into account in all the
      cases, even in the asymptomatic ones.

PMID- 21179925
TI  - Health-related quality of life of diabetic patients.
AB  - Health-related quality of life (HRQOL) provides a multidimensional perspective
      that encompasses a patient's physical, emotional, and social functioning.
      Generally, patients with more than one co-morbid condition report the poorest
      level of HRQOL, but some chronic conditions, like diabetes mellitus, are strongly
      associated with poor HRQOL. Diabetes mellitus permanently changes a patient's
      life. Measures of QOL in chronically ill patients provide an important source of
      medical information in addition to laboratory or diagnostic tests and are
      becoming increasingly relevant to controlled clinical trials. Different
      instruments (questionnaires) have been developed to measure the psychological,
      physical, and social aspects of QOL for diabetes patients.

PMID- 21179926
TI  - Hyposplenism associating long-term asbestos exposure.
AB  - I report a case of functional hyposplenism in a patient with history, and typical
      radiological findings, of asbestos-related lung disease and presenting with
      recurrent pneumococcal pneumonia. Functional hyposplenism is not rare and is
      suspected in cases of recurrent pneumococcal pneumonia and/or sepsis. The two
      most time-honored diseases associated with hyposplenism are celiac disease and
      sickle cell anemia. No cases of functional hyposplenism associating pleural
      and/or parenchymal lung diseases secondary to asbestos exposure have been
      reported to date. Asbestos bodies were reported in the spleen, and multiple other
      extra-pulmonary organs, yet their significance remains uncertain. Asbestos
      exposure may be associated with the development of functional hyposplenism and,
      subsequently, an increased risk of invasive pneumococcal disease.

PMID- 21179927
TI  - An unwanted burden.

PMID- 21179928
TI  - Dental dilemmas: Endodontics or dental implants?
AB  - This narrative review explores treatment planning options in restorative
      dentistry. The growth of dental implants, as an accessible and predictable
      treatment option, gives practitioners a useful tool for managing the missing
      tooth or teeth with a hopeless prognosis. Traditionally, endodontics and fixed
      prosthodontics have been used to restore teeth and spaces where the outlook for
      such treatment appears reasonable. Practitioners may, however, question the
      predictability and cost effectiveness of such an approach where, at times, it
      might appear that replacement of a compromised tooth with a dental implant could
      be a more predictable option. The evidence base for these treatment options is
      explored and discussed, and suggestions are made for future management
      strategies. CLINICAL RELEVANCE: A clear knowledge and understanding of the
      scientific literature for implants and endodontic treatment is necessary if
      practitioners are to make an evidence-based approach when treatment planning
      these modalities for their patients. This is particularly true in cases where
      there may appear to be a reasonable choice between the two of these.

PMID- 21179929
TI  - Why fluoride?
AB  - Fluoride has been used in dentistry for over 100 years for the purpose of
      preventing dental caries. During this time there has been great debate over the
      mode of action, the optimum method of delivery, and the potential risks
      associated with its use. This, the first of three papers, will provide a summary
      of the history of the use of fluoride, the mode of action, benefits and different
      methods of delivery. It will also discuss the potential risk of dental fluorosis.
      CLINICAL RELEVANCE: This article aims to provide a background for general
      practitioners for the appropriate use of fluorides in dentistry, enable them to
      understand the wider significance of fluoride in dentistry and to be able to
      answer non-clinical questions raised by patients.

PMID- 21179930
TI  - Systemic diseases and the elderly.
AB  - Although systemic diseases can occur at any age, they are more common in older
      patients. Accurate and detailed medical and drug histories are important in
      dental practice as many conditions and medications can influence oral health and
      dental care in patients. Not only can these conditions influence patient care in
      the surgery and oral hygiene at home, but access to dental services may also be
      adversely affected. CLINICAL RELEVANCE: The systemic diseases can impact upon
      oral care or can have oral manifestations. Many of the pharmacological
      interventions prescribed for chronic conditions can have multiple and diverse
      adverse effects on the oral environment.

PMID- 21179931
TI  - Occlusal considerations in implantology: good occlusal practice in implantology.
AB  - This article is concerned with implants that are being used for fixed crown and
      bridgework rather than removable prostheses. The huge increase in the provision
      of implants over the past two decades is set to continue. Most of the research is
      related to avoiding failures in implants. This research, in the main, has
      concentrated on the essential interface between the artificial implant and living
      bone: osseointegration. The other interface, which is worthy of our full
      attention, is the one between the implant-supported crown and the antagonist
      tooth: the occlusion. CLINICAL RELEVANCE: This article aims to provide the basis
      for guidelines for good occlusal practice in implantology. It will consider these
      under two headings: those which could be considered as basic occlusal principles;
      and those occlusal considerations that are specific to implants.

PMID- 21179932
TI  - Coronectomy of a third molar with cyst lining enucleation in the management of a
      dentigerous cyst.
AB  - A dentigerous cyst was treated with enucleation and coronectomy of the associated
      tooth to minimize the risk of inferior alveolar nerve damage, resulting from
      direct surgical trauma or indirectly from intra-operative or post-operative jaw
      fracture. Radiographic monitoring over 33 months confirmed migration of the roots
      through healed bone and progressive obliteration of the residual pulp canal
      chamber. These observations are not associated with failure of the technique but
      are, in fact, commonly observed in successful cases of coronectomy. A brief
      discussion of the risks versus benefits of this treatment modality is presented
      with reference to the literature available. CLINICAL RELEVANCE: In selected
      cases, coronectomy with cyst enucleation as a one stage procedure may reduce the
      risk of perioperative nerve damage.

PMID- 21179933
TI  - First aid for orthodontic retainers.
AB  - The need for long-term retention to prevent post-treatment tooth movement is now
      widely accepted by orthodontists. This may be achieved with removable retainers
      or permanent bonded retainers. This article aims to provide simple guidance for
      the dentist on how to maintain and repair both removable and fixed retainers.
      CLINICAL RELEVANCE: The general dental practitioner is more likely to review
      patients over time and needs to be aware of the need for long-term retention and
      how to maintain and repair the retainers.

PMID- 21179934
TI  - Magnifying loupes in modern dental practice: an update.
AB  - There are three principal reasons for adopting magnifying loupes for operative
      dentistry: to enhance visualization of fine detail, to compensate for the loss of
      near vision (presbyopia) and to ensure maintenance of correct posture. The
      wearing of loupes is becoming an accepted norm amongst qualified practitioners
      and increasingly in the undergraduate population. However, further research is
      required before evidence-based recommendations can be made about their
      effectiveness in achieving the three principles. Compared to the medical
      literature, there is a paucity of studies on the use of loupes in dentistry. This
      article presents an overview of the well-documented (but under-researched)
      optical and ergonomic benefits of wearing loupes and highlights special
      circumstances where the use of loupes would be inadvisable. The article concludes
      with a review of the small number of studies on magnifying loupes specifically
      for restorative dentistry. CLINICAL RELEVANCE: The reader should consider the
      information in this article prior to the purchase of magnifying loupes.

PMID- 21179935
TI  - Comprehending the condition, causes, controversies, control and consequences. 1.
      General principles.

PMID- 21179936
TI  - Physical signs for the general dental practitioner. Case 79. 'Venous', 'stasis'
      or 'varicose' ulceration.

PMID- 21179937
TI  - Potential use of nanoparticle based contrast agents in MRI: a molecular imaging
      perspective.
AB  - The development of molecular imaging technologies represents the opportunity to
      differentiate tissues based upon their metabolic and functional activity rather
      than structural and anatomic characteristics. The goal of molecular imaging is to
      reveal the pathophysiology underlying the observed anatomy and to diagnose
      disease based upon early biochemical processes. Detection of pathologic
      biomarkers can lead to early recognition of diseases, better therapeutic
      management, and improved monitoring for recurrence. Among the current clinical
      imaging modalities, MRI is uniquely suited for molecular imaging applications,
      offering a non-invasive means to obtain both anatomic and metabolic/functional
      information with high spatial and temporal resolution. Site-specific MRI contrast
      agents have been developed to target biologic processes that occur early in the
      development of diseases such as atherosclerotic plaques, tumor angiogenesis, and
      disease specific biosignatures. Furthermore, early disease recognition, prompting
      therapeutic intervention and drug delivery evaluation are possible using targeted
      contrast agents.

PMID- 21179938
TI  - Lipid-core nanocapsules as a nanomedicine for parenteral administration of
      tretinoin: development and in vitro antitumor activity on human myeloid leukaemia
      cells.
AB  - Tretinoin-loaded conventional nanocapsules have showed a significant protection
      of this drug against UVC radiation. However, this formulation presents a limited
      stability on storage. We hypothesized that the association of tretinoin to lipid
      core nanocapsules could increase the physicochemical stability of such
      formulations, focusing on the development of a reliable nanomedicine for
      parenteral administration. However, this advantage should still be accompanied by
      the known photoprotective effect of conventional polymeric nanocapsules against
      the exposure of tretinoin to UV radiation. Results showed that tretinoin-loaded
      lipid-core nanocapsules improved the physicochemical stability of formulations
      under storage, without changing their ability to protect tretinoin either against
      UVA or UVC radiation. In addition, the effect of nanoencapsulation on the
      antiproliferative and differentiation properties of tretinoin was studied on
      human myeloid leukemia cells (HL60 cells) showing that tretinoin-loaded lipid
      core nanocapsules presents a longer antitumor efficiency compared to the free
      tretinoin. These results allow us to propose the current formulation (tretinoin
      loaded lipid-core nanocapsules) as a promising parenteral nanomedicine for the
      treatment of acute promyelocytic leukaemia.

PMID- 21179939
TI  - Nuclear translocation of Nrf2 and expression of antioxidant defence genes in THP
      1 cells exposed to carbon nanotubes.
AB  - Carbon nanotubes have a wide range of applications in various industries and
      their use is likely to rise in the future. Currently, a major concern is that
      with the increasing use and production of these materials, there may be increased
      health risks to exposed workers. Long (> 15 microm) straight nanotubes may
      undergo frustrated phagocytosis which is likely to result in reduced clearance.
      We examine here the effects of multiwalled carbon nanotubes of different sizes on
      monocytic THP-1 cells, with regard to their ability to stimulate increased
      expression of the HO-1 and GST genes and their ability to produce nuclear
      translocation of the transcription factor, Nrf2, as well as the release of
      several pro-inflammatory cytokines and mediators of inflammation. Our results
      suggest that long (50 microm) carbon nanotubes (62.5 microg/ml for 4 hours)
      produce increased nuclear translocation of Nrf2 and increased HO-1 gene
      expression compared with shorter entangled nanotubes. There was no increased gene
      expression for GST. The long nanotubes (NT1) caused increased release of the
      proinflammatory cytokine IL-1beta, an effect which was diminished by the
      antioxidant trolox, suggesting a role of oxidative stress in the upregulation of
      this cytokine. Tentatively, our study suggests that long carbon nanotubes may
      exert their effect in THP-1 cells in part via an oxidative stress mechanism.

PMID- 21179940
TI  - Global gene expression analysis of the effects of gold nanoparticles on human
      dermal fibroblasts.
AB  - In order to investigate the molecular effects of gold nanoparticles (GNPs) and
      cell interaction, after human dermal fibroblasts-fetal (HDF-f) treated with GNPs
      for 1, 4 and 8 h, the cytotoxicity was evaluated with methylthiazoltetrazolium
      (MTT) assay. Flow cytometry experiment was used to assess effects of GNPs on cell
      cycle and apoptosis. Differentially expressed genes in HDF-f treated with GNPs
      were obtained using gene expression profile microarray. The gene differential
      expression profile was analyzed by clustering, Gene Ontology (GO) and biological
      pathway. The results from these analyses were integrated to comprehensively
      interpret the data gained from microarray. It suggests that the exposure of HDF-f
      to GNPs might lead to the disturbance of cell cycle regulation, cellular
      oxidative stress and affect regulation of actin cytoskeleton, and other cellular
      activities such as cell adhesion, energy metabolism and signal transduction may
      be also affected. Compared with the cytotoxicological mechanisms induced by Ni2+
      from our previous research and by GNPs from the present study, different
      underlying biological processes and gene regulations were found. The integration
      of microarray and bioinformatics analysis can provide a specific and efficient
      routine to discuss molecular effects of cellular response to biomaterials.

PMID- 21179941
TI  - Effects of chitosan-carboxymethyl dextran nanoparticles on cell proliferation and
      on serum cytokine regulation.
AB  - The bioactivity of chitosan-carboxymethyl dextran nanoparticles (CDNP) made using
      chitosans with different degrees of deacetylation (DA) (CDNP98: CDNP made with
      98% DA chitosan; CDNP78: CDNP made with 78% DA chitosan) were tested by analysis
      of their in vitro effects on HeLa tumor cell and mouse fibroblast proliferation,
      and their in vivo effects on the regulation of mouse serum cytokine levels. CDNPs
      (50 to 100 microg/ml) induced higher fibroblast proliferation than chitosans
      (CDNP98 > CDNP78 > chitosan), and were also more effective than chitosans in
      inhibition of HeLa cell proliferation in a dose-dependent manner (25 to 100
      microg/ml) (CDNP78 > CDNP98 > chitosans). CDNPs also induced a higher serum IL-5
      level than chitosans (CDNP98 > CDNP78 > chitosans) within 3 h, and CDNP78 had a
      greater impact on IL-6 regulation but regulated IL-10 over a shorter duration
      than CDNP98 within the first 3 h. Combined with their ability to reduce serum IL
      17 at 24 h, these biocompatible, immuno-active CDNPs demonstrated the potential
      to be applied as biomedical materials.

PMID- 21179942
TI  - Study on chitosan/polycaprolactone blending vascular scaffolds by
      electrospinning.
AB  - The chitosan/polycaprolactone (CS/PCL) vascular scaffolds were prepared by
      electrospinning in order to combine the advantage of CS and PCL into the vascular
      scaffolds. The obtained CS/PCL vascular scaffolds were dried with ethanol, and
      then characterized by SEM and electronic universal testing machine. The
      endothelial progenitor cells (EPCs) were implanted in the scaffolds with various
      mass ratios of CS to PCL. The vascular scaffolds were examined by adhesion rate
      in different culturing times and the cells growth was observed. Micro/nano
      structured surface of CS/PCL vascular scaffolds are more stable after dealing
      with ethanol. The obtained CS/PCL vascular scaffolds showed porous, micro/nano
      structured surfaces which were similar to natural extracellular matrix. When the
      mass ratio of CS to PCL is 0.5, the breaking elongation of CS/PCL vascular
      scaffolds was 31.64%, and the curves of stress-strain indicate that the obtained
      vascular scaffolds possess good elastic deformation. The adhesion rates of EPCs
      on CS/PCL vascular scaffolds increase to 95.1% in 24 h, the observation of EPCs
      labeled with CM-Dil (chlormethylbenzamido-1,1dioctadecyl-3,3,3',3'
      tetramethylindocarbocyamine) after culturing 72 h by fluorescence microscopy also
      illustrates that CS/PCL vascular scaffolds are beneficial to cell growth and cell
      adhesion.

PMID- 21179943
TI  - Multiwalled carbon nanotubes inhibit fluorescein extrusion and reduce plasma
      membrane potential in in vitro human glioma cells.
AB  - In the study on the interactions of carbon nanotubes with living cells, the cell
      membrane deserves particular attention as it provides the first interface to
      initiate CNTs-cell interactions. In the present study, the inhibiting effect of
      multiwalled carbon nanotubes on the extrusion of fluorescein in human glioma
      cells was demonstrated using two procedures. To provide clues to explanation of
      this effect, intracellular glutathione content and reactive oxygen species
      production were determined as fluorescein is a specific substrate of cell
      membrane multidrug resistance-related protein whose transport activity requires
      glutathione which can be depleted under oxidative stress. The plasma membrane
      potential was also probed as the susceptibility of fluorescein efflux to
      modulation of the plasma membrane potential has been documented. Results showed a
      remarkable decrease in cellular glutathione level as well as an increase in
      reactive oxygen species production. Probe staining also indicated decreased
      plasma membrane potential. The data suggested that multiwalled carbon nanotubes
      may affect the transport activity of cell membrane multidrug resistance-related
      protein through reduction of intracellular glutathione content. Hypopolarization
      of the plasma membrane may also contribute to MWCNTs' effect. Implications of
      these findings are discussed.

PMID- 21179944
TI  - RNA interference-mediated silencing of focal adhesion kinase inhibits growth of
      human colon carcinoma xenograft in nude mice.
AB  - Focal adhesion kinase (FAK), which plays a pivotal role in mediating cell
      proliferation, survival and migration, is frequently overexpressed in human colon
      cancer. In the present study, we utilized the short hairpin RNA (shRNA) to knock
      down the expression of FAK in SW480 human colon cancer cells in vitro.
      Furthermore, nude mice bearing human colon carcinoma SW480 were established and
      treated with plasmids encoding FAK shRNA encapsulated in DOTAP: Chol cationic
      liposome through tail vein injection. Tumor growth and potential side effect were
      observed during the treatment. Assessments of angiogenesis, cell proliferation,
      and apoptosis were performed by using immunohistochemistry against CD31,
      proliferating cell nuclear antigen (PCNA) and TUNEL assays, respectively. The
      results indicated that DOTAP: Chol could efficiently deliver the therapeutic
      plasmids systemically to tumor xenografts, resulting in suppression of tumor
      growth. Treatment with plasmid encoding FAK-targeted shRNA reduced mean tumor
      volume by approximately 86% compared with control groups (p < 0.01), accompanied
      with angiogenesis inhibition (p < 0.05), tumor cell proliferation suppression (p
      < 0.05) and apoptosis induction (p < 0.05). Taken together, our data demonstrated
      that shRNA-mediated silencing of FAK might be a potential therapeutic approach
      against human colon carcinoma.

PMID- 21179945
TI  - Transportation of drug-(polystyrene bead) conjugate by actomyosin motor system.
AB  - The Nanorobotics and cargo transportation application of molecular motors is of
      recent intent. The present study explores the transportation of Mesalamine/5
      aminosalicylic acid/5-ASA drug by molecular motors. Mesalamine is an anti
      inflammatory drug used to treat Crohn's disease and ulcerative colitis. Conjugate
      of mesalamine and polystyrene (Dia.: 3 microm) beads was prepared by amide
      linkage between amine (-NH2) group of drug and carboxyl (-COOH) group of the
      bead. In Fourier Transform Infrared spectra, peaks were observed at 3428.1 and
      1654.0 cm(-1) for N-H and C=O stretching bond respectively confirming the amide
      bond formation between drug and microbeads. Quantification of 5-ASA attached to
      polystyrene bead was done by UV-vis spectroscopy and it was ascertained that 93%
      of 5-ASA was loaded on polystyrene beads. Conjugate of drug-polystyrene beads
      were then covalently attached to actin filaments. Velocity of actin filaments
      attached to drug loaded beads in in-vitro motility assay reduced to 0.89 microm/s
      as compared to free actin velocity (4.64 microm/s). This further ascertains the
      microcomposites formation. The present study provides an insight into the actin
      myosin based molecular motor systems for an efficient tool for drug
      transportation.

PMID- 21179946
TI  - Preparation of magnetic microspheres based on poly(epsilon-caprolactone)
      poly(ethylene glycol)-poly(epsilon-caprolactone) copolymers by modified solvent
      diffusion method.
AB  - Magnetic microspheres have promising application in biomedical field. In this
      paper, biodegradable poly(epsilon-caprolactone)-poly(ethylene glycol)
      poly(epsilon-caprolactone) (PCEC) triblock copolymers were synthesized by ring
      opening polymerization method. Through adjusting the epsilon-CL/PEG weight ratio
      in feed, PCEC copolymers with different block ratio were obtained. A novel
      modified solvent diffusion method was described to prepare magnetic PCEC
      composite microspheres containing magnetite nanoparticles. The particle size of
      microsphere decreased with increase in the PEG/PCL block ratio. The obtained
      microspheres could response to external magnetic field. This study described a
      novel method to prepare magnetic microspheres. The obtained magnetic polymeric
      microspheres might have potential application in drug delivery system or disease
      diagnosis field.

PMID- 21179947
TI  - Development and performance evaluation of amphotericin B transfersomes against
      resistant and sensitive clinical isolates of visceral leishmaniasis.
AB  - The present study was aimed to assess the efficacy of developed transfersome (TF
      3) formulation bearing amphotericin B (AmB) against sensitive and resistant
      clinical isolates of L donovani and compared with conventional liposomal
      formulation (F-2) and free AmB (F-1). The skin permeation of AmB from TF-3 was
      performed using Franz diffusion cell using rat skin which showed fickian
      diffusion across the skin. When tested against L. donovani (intramacrophagic
      amastigotes), it has been observed that TF was more effective than F-1 and F-2
      formulation in sensitive and resistant clinical isolates. The data provides
      evidences that the TF formulation owing to its fluidized behaviour imparted by
      sodium deoxycholate, enables to penetrate well in the infected cells and thus
      provide enhanced activity. The permeation study also supports this data as the
      flux value of AmB through TF formulation was 1.5 fold higher compared to
      conventional liposomes suggesting improved penetration and better partitioning in
      skin layers. Implicit to this preliminary data it is evident that the AmB loaded
      TF formulation has potential as alternate chemotherapeutic approach to control of
      VL. Potential utilities of novel formulation as a transdermal delivery of AmB for
      leishmaniasis necessitates further elaborated investigations which is underway in
      our laboratory.

PMID- 21179948
TI  - Total mercury in wild fish in Guizhou reservoirs, China.
AB  - The health hazard of mercury (Hg) compounds is internationally recognized, and
      the main pathways for methylmercury (MeHg) intake in humans are through
      consumption of food, especially fish. Given the large releases of Hg to the
      environment in China, combined with the fast development of hydropower, this
      issue deserves attention. Provided similar mobilization pathways of Hg in China
      as seen in reservoirs in North America and Europe one should expect increased Hg
      contamination in relation to future hydropower reservoir construction in this
      country. This study presents total Hg (THg) concentrations in wild fish from six
      Guizhou reservoirs, China. The THg concentrations in fish were generally low
      despite high background levels in the bedrock and depositions from local point
      sources. The over all mean +/- SD concentration of THg was (0.066 +/- 0.078)
      microg/g (n = 235). After adjusting for among-reservoir variation in THg, there
      were significant differences in THg among functional groups of the fish, assumed
      to reflect trophic levels. Predicted THg-concentration ratios, retrieved from a
      mixed linear model, between the functional groups were 9:4:4:1 for carnivorous,
      omnivorous, planktivorous and herbivorous fish. This result indicated that MeHg
      accumulation may prevail even under circumstances with short food chains as in
      this Chinese water system. No fish exceeded recommended maximum THg limit for
      human consumption set by World Health Organization and the Standardization
      Administration of China (0.5 microg/g fish wet weight (ww)). Only six fish (2.5%)
      exceeded the maximum THg limit set by US Environmental Protection Agency (0.3
      microg/g fish ww).

PMID- 21179949
TI  - Assessment of mercury(II) bioavailability using a bioluminescent bacterial
      biosensor: practical and theoretical challenges.
AB  - Critical methodological challenges in the microbial biosensor approach to
      assessing Hg(II) bioavailability were evaluated from the perspective of
      analytical chemists. The main challenge stems from the fact that the chemical
      speciation of Hg(II) in natural waters exerts a major control on its
      bioavailability, yet its natural complexation equilibria are extensively altered
      during conventional bioassays. New data, obtained using a bioluminescent Hg(II)
      biosensor, that illustrate these challenges are presented and potential solutions
      proposed.

PMID- 21179950
TI  - Distribution of mercury in different environmental compartments in the aquatic
      ecosystem of the coastal zone of the Southern Baltic Sea.
AB  - The aim of this study was to characterize mercury (Hg) contamination in the
      coastal waters of the Southern Baltic Sea, and to investigate transformations of
      Hg in the initial links of the marine food chain. Concentrations of Hg in water,
      particulate matter, plankton and macrophytes at various stations in the coastal
      zone (a bay with restricted water exchange, near an industrial city, river
      mouths, and the open sea) were measured in 2006-2008. Hg concentrations observed
      in the Southern Baltic varied greatly, showing the highest average values in all
      environmental compartments near the river mouths. In shallow, sheltered parts of
      the gulf, where water exchange is restricted, Hg concentrations in the water and
      in macrophytes were elevated relative to those in the coastal zone of the deeper
      part of the bay and in the open Baltic. Distance to the river mouth, terrestrial
      runoff, and quantity and quality of organic matter were more important than
      seasonal variations in controlling Hg and HgSPM concentrations in water samples.
      Mercury concentrations in the surface microlayer at the air/sea interface were
      over 10 times higher than those in the bulk surface water. Concentrations of Hg
      in macrophytes in the winter were significantly higher than those in the warm
      seasons (spring, summer, autumn). This was probably the combined effect of higher
      availability of Hg in porewaters and leaf growth inhibition.

PMID- 21179951
TI  - Mercury in sediments and vegetation in a moderately contaminated salt marsh
      (Tagus Estuary, Portugal).
AB  - Depth variations of total mercury (Hg) and methylmercury (MeHg) concentrations
      were studied in cores from non-colonized sediments, sediments colonized by
      Halimione portulacoides, Sarcocorniafruticosa and Spartina maritima and
      belowground biomass, in a moderately contaminated salt marsh (Tagus Estuary,
      Portugal). Concentrations in belowground biomass exceeded up to 3 (Hg) and 15
      (MeHg) times the levels in sediments, and up to 198 (Hg) and 308 (MeHg) times
      those found in aboveground parts. Methylmercury in colonized sediments reached 3%
      of the total Hg, 50 times above the maximum values found in non-colonized
      sediments. The absence of correlations between total Hg concentrations in
      sediments and the corresponding MeHg levels suggested that methylation was only
      dependent on the environmental and microbiological factors. The analysis of
      belowground biomass at high-depth resolution (2 cm) provided evidence that Hg and
      MeHg were actively absorbed from sediments, with higher enrichment factors at
      layers where higher microbial activity was probably occurring. The results
      obtained in this study indicated that the biotransformation of Hg to the toxic
      MeHg could increase the toxicity of plant-colonized sediments.

PMID- 21179952
TI  - Factors influencing mercury accumulation in three species of forage fish from
      Caddo Lake, Texas, USA.
AB  - Most studies that have examined mercury (Hg) contamination of fish have focused
      on game species feeding near the top of the food web, while studies that examine
      forage fish that feed near the base of the food web are rare. We conducted a
      survey of Hg contamination in three species of forage fish, brook silverside
      (Labidesthes sicculus), threadfin shad (Dorosoma petenense) and gizzard shad
      (Dorosoma cepedianum), from Caddo Lake, Texas, USA and found species-specific
      differences in Hg concentrations. We examined total length, age, trophic position
      (determined using delta15N), and growth rate of forage fish as factors that could
      have influenced within- and between-species differences in Hg concentration.
      Total length and age were the best predictors of within-species differences in Hg
      concentration. Between-species differences in Hg concentrations were most
      strongly influenced by trophic position.

PMID- 21179953
TI  - Mercury contamination and accumulation in sediments of the East China Sea.
AB  - Mercury (Hg) concentrations in sediment samples collected from the inner and
      middle shelves of the East China Sea (ECS) were analyzed to evaluate Hg
      contamination levels and to calculate Hg sedimentation rates and total
      accumulation in the ECS. The range of Hg concentrations in surface sediments of
      the inner shelf was 26.5-47.6 ng/g, and that for the middle shelf was 4.1-13.9
      ng/g. Hg concentrations correlated well with organic carbon contents but varied
      inversely with sediment grain size. Enrichment factors indicated that the whole
      inner shelf and a small portion of the middle shelf were slightly contaminated by
      Hg. Hg accumulation rates in the ECS ranged between 0.42-48.7 ng/(cm2 x yr), with
      higher values observed in the inner shelf. Total Hg accumulation in the
      calculated area (accounting for 80% of the ECS continental shelf area) ranged
      from 25 to 30 tons/yr; approximately 51% and 17% of the accumulated Hg mass was
      deposited in the Yangtze estuarine zone and the inner shelf, respectively.

PMID- 21179954
TI  - Mercury in an ultraoligotrophic North Patagonian Andean lake (Argentina):
      concentration patterns in different components of the water column.
AB  - The deep, ultraoligotrophic piedmont lakes of Northern Patagonia (Argentina) are
      located in pristine and barely impacted areas, along a wide latitudinal range.
      Several studies have reported moderate to high total mercury (Hg) concentrations
      and contrasting methylmercury (CH3Hg+) production in different lake compartments.
      Sources of Hg for western Patagonian terrestrial and aquatic ecosystems are still
      not clear; while point sources can be ruled out and atmospheric deposition is a
      plausible source, along with contribution from active volcanic areas of the
      Andes. In this investigation, we reported a noticeably seasonal, spatial (between
      lake branches), and vertical (between water column strata) heterogeneity in the
      total Hg concentrations found in the pelagic zone of Lake Moreno. Sterile water
      samples taken in a depth profile of the lake showed moderate to high
      concentrations of CH3Hg+ in autumn with a decreasing trend with depth. Our
      results indicated that Hg is largely allocated in the plankton fraction between
      10-53 microm; which dominated within the euphotic (epilimnetic) zone of the lake
      due to the high densities attained by two species of the dinoflagellate
      Gymnodinium. The 53-200 microm planktonic size fraction (comprising rotifers,
      ciliates and immature stages of crustaceans) and the > 200 microm fraction
      (calanoid copepods and cladocerans) were found to bear strikingly lower total Hg
      concentrations, suggesting that the magnification of Hg at the planktonic
      consumer level is negligible.

PMID- 21179955
TI  - Mercury distribution and bioaccumulation up the soil-plant-grasshopper-spider
      food chain in Huludao City, China.
AB  - The purpose of this study is to investigate total mercury (THg) distribution and
      its bioaccumulation up the soil-plant-grasshopper-spider in the Huludao City,
      which is polluted seriously by chlor-alkali and zinc smelting industry in
      Northeast of China. Results indicated that average THg concentrations in soil,
      plant leaves, grasshopper Locusta migratoria manilensis and Acrida chinensis, and
      spider were 0.151, 0.119, 0.167 and 0.134 mg/kg, respectively. THg spatial
      distribution suggested that most of mercury came from the chlor-alkali plant and
      the two zinc smelteries. The highest mercury concentration was found in the wings
      among different grasshoppers' organs. Although spiders are the predatory, THg
      concentrations in their bodies were not high, and only on the same level as in
      grasshoppers, which might be due to spiders' special living habits. In the light
      of the mercury transportation at every stage of the soil-plant-grasshopper-spider
      food chain, the bioaccumulation factors were 0.03, 0.79-1.11 and 0.80-1.13
      respectively. It suggested that mercury biomagnification up terrestrial food
      chains was not so large and obvious as it was in the aquatic food chain.

PMID- 21179956
TI  - Mercury in some chemical fertilizers and the effect of calcium superphosphate on
      mercury uptake by corn seedlings (Zea mays L.).
AB  - Mercury (Hg) contents in ten chemical fertilizers were determined, and the effect
      of calcium superphosphate (CSP) on the uptake and translocation of Hg in corn
      seedlings was investigated by pot experiments. CSP was applied at the levels of
      0, 66.7, and 133.4 mg P2O5/kg to Hg-treated (2 mg/kg) and untreated soils. CSP
      had the highest Hg content (5.1 mg/kg), followed by the NPK compound fertilizer
      15-5-5 (15% N, 5% P2O5, 5% K2O) (1.2 mg/kg), then by nitrogen fertilizers (except
      for ammonia sulfate) and potassium fertilizers. Application of CSP did not
      obviously influence the biomass of corn roots, but it significantly increased the
      biomass of corn shoots in Hg-treated soil. Application of CSP at the levels of
      66.7 and 133.4 mg P2O5/kg did not obviously influence the uptake of Hg by corn
      seedlings on soils without Hg treatment, but it decreased the Hg uptake of corn
      seedlings significantly on Hg-treated soils. The transfer coefficient of Hg in
      corn seedlings improved slightly on soils without Hg treatment, but decreased
      slightly on Hg-treated soils with the application of CSP. These results implied
      that CSP could ameliorate Hg toxicity to corn seedlings by inhibiting the uptake
      and the translocation of Hg in plants on Hg-polluted soils.

PMID- 21179957
TI  - Trophic transfer of mercury and methylmercury in an aquatic ecosystem impacted by
      municipal sewage effluents in Beijing, China.
AB  - Gaobeidian Lake, located in Beijing, China, serves as a recipient lake for
      effluents from a large municipal sewage treatment plant (MSTP). In order to
      evaluate the effects of discharging MSTP effluent on the mercury contamination of
      the local aquatic ecosystem, sediment cores, water, plankton, fish, and turtle
      samples were collected from Gaobeidian Lake for mercury speciation analysis. High
      concentrations of total mercury (T-Hg) were detected in sediment cores (5.24-17.0
      microg/g dry weight (dw), average: 10.1 microg/g). The ratio of methylmercury
      (MeHg) to T-Hg was less than 0.3% in sediments and ranged from 35% to 76% in
      biota samples. The highest level of T-Hg and MeHg were found in aquatic bryophyte
      and crucian carp (3673 and 437 ng/g dw, respectively). The relative contents of
      MeHg were significantly correlated with trophic levels (R2 = 0.5506, p < 0.001),
      which confirmed that MeHg can be bio-transferred and biomagnified via food chain
      in this aquatic ecosystem.

PMID- 21179958
TI  - Adsorption of atrazine by natural organic matter and surfactant dispersed carbon
      nanotubes.
AB  - The aggregation and dispersion behaviors of carbon nanotubes (CNTs) can regulate
      the environmental spread and fate of CNTs, as well as the organic pollutants
      adsorbed onto them. In this study, multi-walled carbon nanotubes (MWNTs) and
      single-walled carbon nanotubes (SWNTs) were surface modified with humic acids
      from different sources and with surfactants of different ionic types. The
      dispersion stability of surface modified CNTs was observed by UV-Vis
      spectrophotometry. The effect of humic acid and surfactant dispersion on the
      adsorption of atrazine by CNTs was investigated by batch equilibrium experiments.
      Both humic acid and surfactant could effectively disperse MWNTs, but not SWNTs,
      into stable suspensions under the studied conditions. Surface modified CNTs had a
      greatly reduced capacity for adsorption of atrazine. The inhibitory effect of
      peat humic acid was relatively stronger than that of soil humic acid, but the two
      surfactants had a similar inhibitory effect on atrazine adsorption by the two CNT
      types. Increases in surfactant concentration resulted in rapid decreases in the
      adsorption of atrazine by CNTs when the surfactant concentration was less than
      0.5 critical micelle concentration.

PMID- 21179959
TI  - Bacteriological challenges to asbestos cement water distribution pipelines.
AB  - Asbestos cement (AC) pipes were commonly installed in the drinking water
      distribution systems from the mid 1920s to the late 1980s. In recent years, an
      increase in the number of water main breaks has occurred in the AC portions of
      some pipe networks, which can be partially attributed to the corrosion of the
      aged pipes. This study evaluated the potential role that microorganisms may have
      played in the degeneration and failure of AC pipes. In this study, a fresh AC
      pipe section was collected from the distribution network of the City of Regina,
      Canada and examined for microbiological activities and growth on inside surfaces
      of pipe sample. Black slime bacterial growths were found to be attached to inner
      pipe surfaces and a distinctively fibrous internal coating (patina) with iron
      oxides was formed over the time. The microbial populations inside the patina and
      the black slime were tested with BART testers. Heterotrophic aerobic bacteria
      (HAB) and slime forming bacteria (SLYM) dominated in both the black growths and
      inside the patina. Iron related bacteria, denitrification bacteria and sulfate
      reducing bacteria were also commonly present. Microbial challenge assays were
      conducted by submerging the cut segments of the AC pipe into selected bacterial
      cultures for a period of 10 days under both aerobic and anaerobic environments.
      Weight changes were determined and the surface morphology was examined for each
      of the assayed pipe segments. Results indicated that acid producing bacteria,
      SLYM and HAB could facilitate the pipe weight loss under anaerobicenvironments.

PMID- 21179960
TI  - Decolorization of molasses melanoidins and palm oil mill effluent phenolic
      compounds by fermentative lactic acid bacteria.
AB  - Lactobacillus plantarum SF5.6 is one of the lactic acid bacteria (LAB) that has
      the highest ability of molasses melanoidin (MM) decolorization among the 2114
      strains of LAB. The strains were isolated from spoilage, pickle fruit and
      vegetable, soil and sludge from the wastewater treatment system by using
      technical step of enrichment, primary screening and secondary screening. This LAB
      strain SF5.6 was identified by 16S rDNA analysis and carbohydrate fermentation
      (API 50 CH). The top five LAB strains having high MM decolorization (> 55%),
      namely TBSF5.8-1, TBSF2.1-1, TBSF2.1, FF4A and SF5.6 were selected to determine
      the optimal condition. It was found that the temperature at 30 degrees C under
      facultative conditions in GPY-MM medium (0.5% glucose, 0.1% peptone, 0.1% yeast
      extract, 0.1% sodium acetate, 0.05% MgSO4 and 0.005% MnCl2 in MM solution at pH
      6) giving a high microbial growth and MM decolorization for all five strains. It
      was noticed that the decolorization of MM by LAB strains might be cell growth
      associated. L. plantarum SF5.6 grew rapidly within one day while the other
      strains took 2-3 days. This L. plantarum SF5.6 could rapidly decolorize MM to
      60.91% without any lag phase, and it also had the ability to remove 34.00%
      phenolic compounds and 15.88% color from treated palm oil mill effluent.

PMID- 21179961
TI  - Modeling of secondary treated wastewater disinfection by UV irradiation: effects
      of suspended solids content.
AB  - This work aimed to study UV-resistant strains of Pseudomonas aeruginosa, to
      propose a formulation of the kinetics of secondary treated wastewater
      disinfection and to underline the influence of suspended solids on the
      inactivation kinetics of these strains. Some investigations were carried out for
      the validation of some simulation models, from the simplest, the kinetics model
      of Chick-Watson reduced to first order, to rather complex models such as multi
      kinetic and Collins-Selleck models. Results revealed that the involved processes
      of UV irradiation were too complex to be approached by a simplified formulation,
      even in the case of specific strains of microorganisms and the use of nearly
      constant UV radiation intensity. In fact, the application of Chick-Watson model
      in its original form is not representative of the kinetics of UV disinfection.
      Modification, taking into account the speed change during the disinfection
      process, has not significantly improved results. On the other hand, the
      application of Collins-Selleck model demonstrates that it was necessary to exceed
      a least dose of critical radiation to start the process of inactivation. To
      better explain the process of inactivation, we have assumed that the action of
      disinfectant on the survival of lonely microorganisms is faster than its action
      on suspended solids protected or agglomerated to each others. We can assume in
      this case the existence of two inactivation kinetics during the processes
      (parallel and independent) of the first-order. For this reason, the application
      of a new kinetic model by introducing a third factor reflecting the influence of
      suspended solids in water on disinfection kinetics appeared to be determinant for
      modeling UV inactivation of P. aeruginosa in secondary treated wastewater.

PMID- 21179962
TI  - Microbial community variation in phytoremediation of triazophos by Canna indica
      Linn. in a hydroponic system.
AB  - Phytoremediation of triazophos (O,O-diethyl-O-(1-phenyl-1,2,4-triazole-3-base)
      sulfur phosphate, TAP) pollution by Canna indica Lim. in a hydroponic system has
      been well studied, whereas the microbial mechanism on TAP degradation is still
      unknown. The variation in microbial community compositions was investigated by
      analyzing phospholipid fatty acids (PLFAs) profiles in microbes under TAP
      exposure. The TAP exposure resulted in an increase in proportions of fatty acid
      16:0 and decrease in fatty acid 18:2omega9,12c, indicating that TAP may stimulate
      the reproduction of microorganisms and inhibit the growth of fungi to some
      degree. Significant correlation was found between the ratio of fungi to bacteria
      and TAP removal (r2 = 0.840, p < 0.01). In addition, the microbial community in
      the phytoremediation system with C. indica was dominated by Gram negative
      bacteria, which possibly contributed to the degradation of TAP. These results
      indicated that TAP might induce the colonization of bacteria in the hydroponic
      system planted with C. indica, and lead to a discrimination of microbial
      community, which might be one of the mechanisms on TAP dissipation in
      phytoremediation system.

PMID- 21179963
TI  - Diversity of methanotrophs in Zoige wetland soils under both anaerobic and
      aerobic conditions.
AB  - Zoige wetland is one of the most important methane emission centers in China. The
      oxidation of methane in the wetland affects global warming, soil ecology and
      atmospheric chemistry. Despite their global significance, microorganisms that
      consume methane in Zoige wetland remain poorly characterized. In this study, we
      investigated methanotrophs diversity in soil samples from both anaerobic site and
      aerobic site in Zoige wetland using pmoA gene as a molecular marker. The cloning
      library was constructed according to the pmoA sequences detected. Four clusters
      of methanotrophs were detected. The phylogenetic tree showed that all four
      clusters detected were affiliated to type I methanotrophs. Two novel clusters
      (cluster 1, cluster 2) were found to relate to none of the recognized genera of
      methanotrophs. These clusters have no cultured representatives and reveal an
      ecological adaptation of particular uncultured methanotrophs in Zoige wetland.
      Two clusters were belonging to Methylobacter and Methylococcus separately.
      Denaturing gradient gel electrophoresis gel bands pattern retrieved from these
      two samples revealed that the community compositions of anaerobic soil and
      aerobic soil were different from each other while anaerobic soil showed a higher
      metanotrophs diversity. Real-time PCR assays of the two samples demonstrated that
      aerobic soil sample in Zoige wetland was 1.5 times as much copy numbers as
      anaerobic soil. These data illustrated that methanotrophs are a group of
      microorganisms influence the methane consumption in Zoige wetland.

PMID- 21179964
TI  - Growth and photosynthesis responses of Phaeodactylum tricornutum to dissolved
      organic matter from salt marsh plant and sediment.
AB  - The effects of allochthonous dissolved organic matter (DOM) on the growth and
      photosynthesis of Phaeodactylum tricornutum were investigated. P. tricornutum
      incubated in f/2 medium was exposed to DOM additives, which were extracted from
      the plant and sediment samples of a salt marsh in North Branch of the Yangtze
      estuary, China. During 12 days incubation, the chlorophyll fluorescence
      parameters of P tricornutum were measured by a Phyto-PAM phytoplankton analyzer.
      Spectral properties of DOM in algae filtrates were also observed. The
      concentrations of chlorophyll a, active chlorophyll a, and the maximum quantum
      yield of photosystem II significantly decreased after four days of incubation,
      suggesting that the growth and photosynthetic efficiency of P. tricornutum were
      inhibited. After adding sediment-DOM extract, both a250/a365 (the ratio of the
      absorption coefficients at 250 and 365 nm) and S values (spectral slope
      coefficients) of algae filtrates declined in the first two days, which
      demonstrated a loss of low molecular weight DOM. Parallel factor analysis of
      fluorescence spectra of DOM in algae filtrates revealed that DOM could be
      classified into two humic-like and two protein-like components. The fluorescence
      intensity of tyrosine-like component originating from algae increased
      significantly during incubation. This study supports the hypothesis that
      allochthonous DOM derived from salt marsh plant and sediment have a strong
      influence on the adjacent aquatic ecosystems.

PMID- 21179965
TI  - Genotypic variations in the accumulation of Cd exhibited by different vegetables.
AB  - It is an important approach to use the Cd-contaminated soils properly by growing
      low accumulator or excluder plants for Cd to produce safe foods. To find the
      suitable vegetable species for growing in Cd-contaminated soils, in the present
      study the variations in the Cd accumulation for twenty eight vegetable species
      and several cultivars of five common vegetables (cowpea, kidney pea, bitter
      gourd, cucumber and squash) were investigated in two soil Cd levels (1 and 2
      mg/kg Cd). Experimental results showed that highly significant differences in Cd
      concentration were evident among 28 vegetables. For example, spinach Cd
      concentrations were 110-fold and 175-fold higher than that of sweet pea under the
      1 and 2 mg/kg Cd exposures, respectively. For Cd accumulation, the order of
      vegetable species was: leafy vegetables > solanaceous vegetables > kale
      vegetables > root vegetables > allimus > melon vegetables > legumes. Distinctive
      differences were also identified when comparing different cultivars of the five
      common vegetables with an average range of 0.003-0.094 mg/kg Cd. Our results
      indicated that a large genotypic variation existed among vegetable species or
      cultivars when subjected to Cd exposure. Therefore, it is important and feasible
      to elect/breed vegetable species/cultivars with low accumulation of Cd,
      especially in mildly Cd-contaminated soils.

PMID- 21179966
TI  - Effect of lime application on microbial community in acidic tea orchard soils in
      comparison with those in wasteland and forest soils.
AB  - Lime application is a conventional technology to control acidification in tea
      orchard soils. We investigated the effect of lime application on soil microbial
      community diversity in the soils of three tea orchards, wasteland and forest. The
      BIOLOG data showed that both the average well color development of all carbon
      sources and the functional diversity index increased with the liming rate in the
      tea orchards and the forest, but decreased in the wasteland. The phospholipid
      fatty acid (PLFA) analysis showed that the structural diversity index of soil
      microbial community increased with the liming rate in all the tea orchards, the
      wasteland and the forest. Lime application also increased the soil-bacterial PLFA
      content in all the soils. Soil fungal and actinomycete PLFAs in the tea orchards
      showed an increasing trend from 0 to 3.2 g CaCO3/kg application and then a
      decreasing trend from 3.2 to 6.4 g CaCO3/kg application. The principal component
      analysis of BIOLOG and PLFA data suggested that lime application had a
      significant effect on soil microbial community structure, and land use had a
      greater effect on soil microbial community structure compared to lime
      application.

PMID- 21179967
TI  - Simultaneous detection of enteroviruses from surface waters by real-time RT-PCR
      with universal primers.
AB  - In order to realize simultaneous quantitative detection of various enteroviruses
      from water samples, a real-time reverse transcription-polymerase chain reaction
      (real-time RT-PCR) method was developed with universal primer pairs designed
      based on the highly conserved non-coding region sequences of genome targeting
      poliovirus, coxsackievirus and enterovirus 71. The recombinant plasmid was
      constructed as enterovirus DNA standard by cloning poliovirus cDNA into a pMD18-T
      vector. The real-time RT-PCR method utilizing SYBR Green I was optimized. As a
      result of a series of examinations, the detection limit of the method was found
      to be 2.31 genome equivalent copy (GEC)/microL, the intra- and inter-assay
      variations were lower than 2% and 5%, respectively, and enteroviruses were well
      distinguished from other microorganisms. There was a good linear relationship (r2
      = 0.997) between the logarithm of viral density and cycle threshold in a wide
      range of 2.31 x 10(0) to 2.31 x 10(9) GEC/microL. The validity of the method was
      further proved by its application for the detection of enteroviruses from various
      practical water samples.

PMID- 21179968
TI  - Preparation and characterization of biomimetic adsorbent from poly-3
      hydroxybutyrate.
AB  - Biomimetic adsorbent named as PHBBMA was prepared from lipophilic poly-3
      hydroxybutyrate (PHB) by a modified double emulsion solvent evaporation method.
      PHBBMA, characterized by using scanning electron microscope and nitrogen
      adsorption/desorption measurements, is porous spherical particles. The
      characterization with the thermal gravimetric analysis and differential scanning
      calorimetry, 1H nuclear magnetic resonance and Fourier transform infrared
      spectroscopy showed that PHBBMA preparation was a physical process without
      chemical reaction. The adsorption of PHBBMA for o-nitrochlorobenzene (o-NCB) was
      fitted better by Langmuir model than by Freundlich model, while the pseudo second
      order model fitting was better than the pseudo first-order model fitting. The
      maximal adsorption capacity of PHBBMA for o-NCB was 57.83 mg/g at 30 degrees C,
      although its specific surface area (S(BET)) was only 8.45 m2/g. PHBBMA is a safe
      and environmental friendly adsorbent with high adsorption capacity because its
      component is innocuous and biodegradable PHB produced reusing wastes and
      contaminants, no byproduct can produced, and its ester and hydrocarbyl groups
      have strong affinity with organochlorine compounds. The further work will focus
      on the modification and improvement of PHBBMA in order to increase its SBET and
      adsorption capacity.

PMID- 21179969
TI  - Application of activated carbon derived from scrap tires for adsorption of
      Rhodamine B.
AB  - Activated carbon derived from solid hazardous waste scrap tires was evaluated as
      a potential adsorbent for cationic dye removal. The adsorption process with
      respect to operating parameters was investigated to evaluate the adsorption
      characteristics of the activated pyrolytic tire char (APTC) for Rhodamine B
      (RhB). Systematic research including equilibrium, kinetics and thermodynamic
      studies was performed. The results showed that APTC was a potential adsorbent for
      RhB with a higher adsorption capacity than most adsorbents. Solution pH and
      temperature exert significant influence while ionic strength showed little effect
      on the adsorption process. The adsorption equilibrium data obey Langmuir isotherm
      and the kinetic data were well described by the pseudo second-order kinetic
      model. The adsorption process followed intra-particle diffusion model with more
      than one process affecting the adsorption process. Thermodynamic study confirmed
      that the adsorption was a physisorption process with spontaneous, endothermic and
      random characteristics.

PMID- 21179970
TI  - Optimization of parameters on photocatalytic degradation of chloramphenicol using
      TiO2 as photocatalyst by response surface methodology.
AB  - The experimental design methodology was applied for modeling and optimizing the
      operation parameters on photocatalytic degradation of chloramphenicol (CAP) using
      TiO2 as photocatalyst in a photoreactor. Three experimental parameters (including
      pH, TiO2 concentration and CAP initial concentration) were adopted to obtain the
      preliminary information. The multivariate experimental design was employed to
      establish a quadratic model as a functional relationship between the degradation
      rate of CAP and three experimental parameters. The interaction effects and
      optimal parameters were obtained by using Design Expert software. The optimal
      values of the operation parameters under the related constraint conditions were
      found at pH 6.4, TiO2 concentration of 0.94 g/L and CAP initial concentration of
      19.97 mg/L, respectively. The degradation rate of CAP approached 85.97% under
      optimal conditions. The regression analysis with R2 value of 0.9519 had a good
      agreement between the experimental results and the predictive values. In
      addition, pH and TiO2 concentration had a significant influence on the
      degradation rate of CAP.

PMID- 21179971
TI  - Activated carbon supported TiO2-photocatalysis doped with Fe ions for continuous
      treatment of dye wastewater in a dynamic reactor.
AB  - Fe-doped TiO2 coated on activated carbon (Fe-TiO2/AC, FTA) composites were
      prepared by an improved sol-gel method and characterized by scanning electron
      microscopy, X-ray photoelectron spectroscopy, X-ray diffractometry, inductively
      coupled plasma mass spectrometry and BET surface area analysis. Obtained FTA
      composites were applied to the continuous treatment of dye wastewater in a
      dynamic reactor. The effects of Fe ion content, catalyst content, UV-lamp power
      and flowrate of the continuous treatment of dye wastewater on degradation
      efficiency were analyzed to determine the optimum operating conditions of dye
      wastewater degradation. Continuous photocatalytic experiments provided
      interesting results that VIFTA had a high chemical oxygen demand (COD) removal
      rate compared with TiO2, Fe doped TiO2 (FT) and TiO2 coated on activated carbon
      (TA). In particular, when using the FTA catalyst with a Fe ion content of 0.33%,
      the kinetic content (k = 0.0376) of COD removal was more than the sum of both TA
      (0.0205) and 0.33% FT (0.0166). FTA showed a high photoactivity because of a
      synergistic effect between Fe ions and AC on TiO2, which is higher than the
      individual effects of AC or Fe ions on TiO2. Additionally, for the photocatalytic
      degradation of dye wastewater, the optimum Fe ion content, catalyst content, UV
      lamp power and flowrate were 0.33%, 6 g/L, 60 W (two lamps) and 300 mL/hr,
      respectively. An investigation of catalyst reuse revealed that the 0.33% FTA
      showed almost no deactivation in photocatalytic degradation of naturally treated
      wastewater.

PMID- 21179972
TI  - Evaluating Beijing's human carrying capacity from the perspective of water
      resource constraints.
AB  - As the demands on limited water resources intensify, concerns are being raised
      about the human carrying capacity of these resources. However, few researchers
      have studied the carrying capacity of regional water resources. Beijing, the
      second-largest city in China, faces a critical water shortage that will limit the
      city's future development. We developed a method to quantify the carrying
      capacity of Beijing's water resources by considering water-use structures based
      on the proportions of water used for agricultural, industrial, and domestic
      purposes. We defined a reference structure as 45:22:33 (% of total,
      respectively), an optimized structure as 40:20:40, and an ideal structure as
      50:15:35. We also considered four domestic water quotas: 55, 75, 95, and 115
      m3/(person x yr). The urban carrying capacity of 10-12 million was closest to
      Beijing's actual 2003 population for all three water-use structures with urban
      domestic water use of 75 m3/(person x yr). However, after accounting for our
      underlying assumptions, the adjusted carrying capacity is closer to 5-6 million.
      Thus, Beijing's population in 2003 was almost twice the adjusted carrying
      capacity. Based on this result, we discussed the ecological and environmental
      problems created by Beijing's excessive population and propose measures to
      mitigate these problems.

PMID- 21179973
TI  - Prognostic significance of ambulatory arterial stiffness index in hypertensives
      followed for 8.2 years: its relation with new events and cardiovascular risk
      estimation.
AB  - INTRODUCTION: The ambulatory arterial stiff ness index (AASI) is a new method for
      estimating arterial stiffness, which is associated with cardiovascular (CV)
      prognosis. Our aim was to evaluate the prognostic significance of AASI for new CV
      events. METHODS: Casual and ambulatory blood pressure (BP) measurements were
      obtained in 1200 hypertensive patients (645 female, age 51 +/- 12 years, BMI 27
      +/- 5 kg/m2), 53% under stabilized therapy, 47% untreated, all without previous
      CV events. The occurrence of CV events was determined for 9833 patient-years and
      analyzed by a Cox proportional hazard model adjusted for confounding variables.
      AASI was calculated from 24h ABPM data and all patients were classified from very
      high to average CV risk. RESULTS: There were 62 deaths and 152 new fatal and non
      fatal CV events (79 strokes, 51 coronary events, 22 other CV events) during the
      15.2 years of follow-up (mean 8.2 +/- 3.0 years). AASI correlated significantly
      (p < 0.001) with pulse wave velocity (PWV), casual and 24h ambulatory BP, age and
      BMI. In subjects with very high or high CV risk (n = 401), AASI was 0.338 +/-
      0.178, while in those with low or moderate CV risk (n = 715), it was 0.291 +/-
      0.173 and in those with average CV risk (n = 84), it was 0.219 +/- 0.170) (p <
      0.002, ANOVA). The probability of event-free and stroke-free survival (Kaplan
      Meier) was better for AASI values below vs. above the median. The adjusted
      relative risk (HR 95% CI) for CV events, stroke and coronary events associated
      with a 1-SD increment in AASI values was respectively 1.27 (1.01-1.59), 1.36 (95%
      CI 1.02-1.89) (p < 0.02) and 0.99 (95% CI 0.67-1.48) (NS), similar to that of 24h
      pulse pressure (PP) and PWV. AASI hazard ratios were no longer significant after
      additional adjustment for 24h PP, whereas the converse did not occur. However,
      AASI above the median increases the predictive value of 24h PP for CV events and
      stroke. CONCLUSIONS: AASI correlates with PWV, stratifies CV risk and predicts
      total cardiovascular events and stroke but not coronary events. AASI may add
      predictive value to 24h PP for CV events and stroke.

PMID- 21179975
TI  - Contribution of CPET to prognostic assessment of patients with left ventricular
      systolic dysfunction.

PMID- 21179974
TI  - Combining ventilatory efficiency and peak oxygen consumption in the prognostic
      assessment of patients with chronic heart failure.
AB  - Cardiopulmonary exercise testing (CPET) is an objective method for assessment of
      functional capacity and for prognostic stratification of patients with chronic
      heart failure (CHF). In this study, we analyzed the prognostic value of a
      recently described CPET-derived parameter, the minute ventilation to carbon
      dioxide production slope normalized for peak oxygen consumption (VE/VCO2
      slope/pVO2). METHODS: We prospectively studied 157 patients with stable CHF and
      dilated cardiomyopathy who performed maximal CPET using the modified Bruce
      protocol. The prognostic value of VE/VCO2 slope/pVO2 was determined and compared
      with traditional CPET parameters. RESULTS: During follow-up 37 patients died and
      12 were transplanted. Mean follow-up in surviving patients was 29.7 months (12
      36). Cox multivariate analysis revealed that VE/VCO2 slope/pVO2 had the greatest
      prognostic power of all the parameters studied. A VE/VCO2 slope/pVO2 of > or =
      2.2 signaled cases at higher risk. CONCLUSION: Normalization of the ventilatory
      response to exercise for peak oxygen consumption appears to increase the
      prognostic value of CPET in patients with CHF.

PMID- 21179976
TI  - Impact of renal function on mortality and incidence of major adverse
      cardiovascular events following acute coronary syndromes.
AB  - BACKGROUND: Renal failure patients have a dismal prognosis in the setting of
      acute coronary syndromes (ACS). Several studies have shown that this population
      is undertreated, benefiting less frequently from cardiovascular agents and
      interventions. The aim of our study was to evaluate patients hospitalized for ACS
      who also presented renal dysfunction, identifying baseline clinical
      characteristics, treatment options and prognosis. We also assessed whether renal
      failure was an independent predictor of mortality and cardiovascular events.
      METHODS: We performed an observational, longitudinal, prospective and continuous
      study, including 1039 consecutive patients hospitalized in a single center for
      ACS. Two groups were compared according to estimated glomerular filtration rate
      (eGFR): eGFR > or = 60 ml/min (group A) and eGFR < 60 ml/min (group B). The mean
      follow-up was twelve months after discharge. Multivariate analysis was used to
      identify predictors of mortality and major adverse cardiovascular events (MACE)
      in this population. RESULTS: Group B patients were older and more frequently
      female, and presented a higher prevalence of cardiovascular risk factors and
      previous cardiovascular disease, and more severe coronary artery disease. Group B
      also had more cases of non-ST-elevation acute myocardial infarction, as well as
      higher blood glucose, higher heart rate on admission, and lower left ventricular
      ejection fraction. Patients in group B were less frequently treated with the main
      cardiovascular drugs or by an invasive strategy; this group also presented higher
      in-hospital mortality (9.1 vs. 2.5%, p < 0.001). During clinical follow-up,
      survival and MACE-free rates were significantly lower in group B patients (86.6
      vs. 93.6%, p < 0.001, and 76.2 vs. 86.2%, p < 0.001, respectively). Multivariate
      analysis showed that eGFR of < 30 ml/min was an independent predictor of in
      hospital mortality (OR 6.92; C statistic = 0.87) and that eGFR of < 60 ml/min was
      an independent predictor of MACE during follow-up (OR 2.19; C statistic = 0.71).
      CONCLUSION: We found that moderate to severe renal dysfunction is common in ACS
      patients, and this variable was an independent predictor of mortality and MACE.
      However, we also found that these patients are undertreated, which may contribute
      to their poor prognosis. Early identification of these high-risk patients is
      important so that the procedures recommended in the international guidelines can
      be more consistently implemented.

PMID- 21179977
TI  - Renal dysfunction in acute coronary syndrome--an epidemic for the 21st century?

PMID- 21179978
TI  - Impact of intraoperative transesophageal echocardiography in cardiac surgery:
      retrospective analysis of a series of 850 examinations.
AB  - OBJECTIVE: To evaluate the impact of intraoperative transesophageal
      echocardiography (TEE) on surgical decisions patients undergoing cardiac surger
      in a Portuguese hospital. METHODS: The authors retrospectively analyzed a series
      of 850 examinations performed between 2003 and 2009 in patients who underwent
      different cardiac surgical procedures. Medical records and TEE reports were
      reviewed to determine whether new information was found and whether this changed
      the surgical plan. RESULTS: Intraoperative TEE revealed new information in 32% of
      the study population and had surgical impact in 29% of all patients. TEE had the
      greatest impact in class I indications, but its use in class II indications also
      had a significant impact. No cases of morbidity or mortality were found.
      CONCLUSIONS: Our findings suggest that intraoperative TEE should be used
      routinely in all patients undergoing cardiac surgery.

PMID- 21179979
TI  - Female gender: an independent factor in ST-elevation myocardial infarction.
AB  - INTRODUCTION: Cardiovascular disease is the leading cause of death in women. In
      ST-elevation myocardial infarction (STEMI) in particular, the question has been
      raised whether specific characteristics of women confer a worse prognosis.
      OBJECTIVE: To evaluate the differences in STEMI patients between the genders in
      cardiovascular risk profile, clinical presentation, therapeutic approach and in
      hospital and 6-month mortality rates. METHODS: We analyzed 1578 patients admitted
      consecutively with STEMI during a 7-year period (from January 13, 2002 to
      December 31, 2008). The patients were divided into two groups according to
      gender, and compared in terms of baseline clinical and demographic
      characteristics, pre-hospital and in-hospital delay, clinical presentation on
      admission, reperfusion therapy, severity of coronary disease and in-hospital and
      6-month mortality. RESULTS: Of the 1578 patients, 26% were female. Women were
      older (by 8 years), and had a higher cardiovascular risk profile. On admission,
      their clinical presentation was more severe, with a higher frequency of anterior
      myocardial infarction and acute heart failure symptoms. Women had longer ischemic
      times and lower rates of reperfusion therapy. Mortality in women was
      significantly higher than in men, both in-hospital (17.5 vs. 5.3%) and at 6
      months (23.5% vs. 8.2%). After adjustment in multivariate analysis, mortality in
      women remained higher. CONCLUSIONS: The adverse demographic and clinical profile
      could partially explain the worse prognosis of STEMI in women. This, together
      with longer pre-hospital delays, led to underuse of reperfusion therapy. Even so,
      female gender by itself had a negative and independent influence on mortality in
      STEMI patients.

PMID- 21179980
TI  - The importance of echocardiography in the diagnosis and treatment of ostium
      secundum-type atrial septal defect.
AB  - Ostium secundum-type atrial septal defect (osASD) is one of the most common
      congenital heart defects. Treatment of these defects was revolutionized by the
      introduction of percutaneous closure. Echocardiography has a major role in the
      evaluation and treatment of this disease. The authors review the role of this
      imaging technique in diagnosis and in treatment decisions, as well as its
      advantages in monitoring and follow-up of percutaneous closure. In this context,
      we present our center's experience with different types of echocardiography,
      namely transthoracic, transesophageal and intracardiac, in closure of osASD.

PMID- 21179981
TI  - Giant interatrial septal aneurysms mimicking quistic masses. Two cases with
      different therapeutic options.
AB  - With the recent technical improvement in echocardiography imaging (second
      harmonics) the number of interatrial septum aneurysms (ASA) increased and are
      easily recognized. We assist to an overdiagnosing number of cases and diagnostic
      criteria emerged to face this problem. In the great majority of the cases ASA are
      small and inoffensive, but as ASA is considered a risk factor for cardioembolism
      when associated with persistence of foramen oval (PFO), an examination by
      transesophageal echocardiography (TEE) for exclusion of PFO makes the sense and
      is a common testing in patients with cryptogenic stroke. Besides these frequent
      ASA, other forms exist; the authors describe two cases of uncommon and huge ASA,
      one mimicking a right atrial tumor and the other a quistic, hipoechoic mass. The
      first case was associated with mitral stenosis and was submitted to surgery and
      the second was closed with an Amplatzer occluder device usually used in atrial
      septal defect (ASD).

PMID- 21179982
TI  - A review of the imaging and intervention of liver transplant complications.
AB  - Liver transplantation has become a successful surgical solution to a variety of
      medical and oncological parenchymal liver diseases. As a result, these patients
      are being encountered more frequently within diagnostic imaging departments which
      may be remote from the transplant centre. Radiologists must therefore be
      proficient in identifying normal post-transplant anatomy which involves the
      anastomosis of four structures between the donor and recipient, namely the
      hepatic artery, the main portal vein, the retro-hepatic inferior vena cava and
      the extra-hepatic bile ducts. A number of potential complications can arise
      involving any or all of these structures, which can be potentially devastating
      and lead to graft failure. Radiologists must familiarise themselves with the
      normal post-operative appearances of liver transplantation and become competent
      in diagnosing post-transplant complications. Where possible, complications should
      be treated using interventional radiological techniques, thus avoiding the need
      for repeat surgical intervention or retransplantation.

PMID- 21179983
TI  - Pathologic assessment of non-palpable probably benign breast masses at
      sonography: can instant intervention be avoided and is follow-up adequate?
AB  - AIM OF THE STUDY: To evaluate the pathologic results, determine the negative
      predictive value of non-palpable probably benign lesions at ultrasound and asses
      whether follow-up is adequate and immediate biopsy can be avoided. MATERIALS AND
      METHODS: Four hundred and eight cases which were referred to our breast imaging
      unit between 2004 and 2008 for biopsy evaluation were enrolled into the study.
      Two hundred and thirteen probably benign solid masses are classified as BI-RADS 3
      in 205 of the enrollees. All masses were sonographically detectable and were
      classified through the guidelines of BI-RADS lexicon for sonography before the
      final pathological examination. All pathologic results were evaluated and the
      negative predictive value, false negativity rate and 95% confidence interval were
      calculated. RESULTS: Of the 213 masses, fine needle aspiration cytology was
      performed in 120. US-guided wire localization and eventual surgery were carried
      out in the remaining 93 masses. Finally, 211 of the punctured lesions turned out
      to be benign and only two malignant lesions were detected. The resulting negative
      predictive value was found to be 99.1% while the false negative rate value was
      0.9%. CONCLUSION: With the results provided, we think that in the patients with
      sonographically detected probably benign breast lesions, short-term follow-up
      seems to be a strong alternative to immediate biopsy with its reliable high
      negative predictivity as well as low false negativity.

PMID- 21179984
TI  - MR imaging findings of haemophilic arthropathy of the elbow in children.
AB  - Haemophilic arthropathy of the elbow is a rare cause of elbow pain in children
      and adolescents. The purpose of this study is to determine the MR appearance of
      the spectrum of lesions found in haemophilic arthropathy of the elbow at initial
      MR imaging. It is important to be aware of the early changes in this entity,
      since early diagnosis and treatment of the disease may prevent progressive joint
      destruction.

PMID- 21179985
TI  - CT angiography evaluation of the renal vascular pathologies: a pictorial review.
AB  - The emergence of CT angiography (CTA) has a groundbreaking impact on the
      evaluation of renal vessels and is gradually replacing the conventional catheter
      angiography as the standard imaging procedure. In this review, we aimed to
      describe the renal CTA technique and imaging findings of several renal arterial
      (i.e. atherosclerosis, fibromuscular dysplasia, aneurysms of the renal arteries,
      dissection, vasculitidis, follow-up of patients with renal arterial stent) and
      venous (i.e. nut-cracker syndrome, pelvic congestion syndrome) pathologies.

PMID- 21179986
TI  - Familial renal retroperitoneal lymphangiomatosis: personal experience and review
      of literature.
AB  - Lymphangiomatosis of the kidneys and perirenal-retroperitoneal tissues is a rare
      disease of unknown etiology. We present two cases affecting members of the same
      family, supporting the familial nature of the disease. The natural history and
      related urological and systematic complications of the disease during a long-term
      follow-up are highlighted, while a comprehensive literature review is presented.

PMID- 21179987
TI  - Metallic staples line mimicking a retained surgical sponge.
AB  - The inadvertent loss of surgical sponges remains a dreadful hazard of surgery. We
      report the case of a patient with a medical history of myotonic dystrophy type 1
      who had received a right upper lobectomy for the treatment of a stage IIA
      (pT1N1M0) well differentiated neuroendocrine carcinoma. In the early
      postoperative period, aspiration of gastric contents occurred and the patient
      underwent endotracheal intubation and mechanical ventilation. A follow-up multi
      detector computed tomography (MDCT) scan of the chest showed a complex mass in
      interlobar position with an internal radiopaque serpiginous thread of metallic
      density which was assumed to represent a retained surgical sponge. Upon surgical
      exploration, no retained foreign body was found and a zone of recent hemorrhagic
      infarction, bordered by the line of the mechanical staples used to complete the
      minor fissure, was removed from the middle lobe. When evaluating patients
      suspected of having a retained surgical sponge, thoracic surgeons and
      radiologists should be aware of this potential source of confusion.

PMID- 21179988
TI  - Wegener granulomatosis masquerading as pneumonia.
AB  - We report a case of an elderly patient with a limited form of Wegener
      granulomatosis, which simulated the clinical and imaging features of organizing
      pneumonia. Here we call attention to this atypical case presentation that
      eloquently illustrates the many faces of Wegener granulomatosis.

PMID- 21179989
TI  - The roots of radiology in Greece.
AB  - This article presents as reliably as possible the roots of the Radiology
      specialty in Greece, from the time of the discovery of X-rays by WC Roentgen. It
      mentions the most important dates relevant to the foundation of the specialty of
      Radiology in Greece.

PMID- 21179990
TI  - Epiploic appendagitis within a Spigelian hernia.

PMID- 21179991
TI  - Extra-adrenal retroperitoneal ganglioneuroma.

PMID- 21179992
TI  - Unusual vacuum phenomenon suggesting occult vertebral instability.

PMID- 21179993
TI  - Terson's syndrome.

PMID- 21179994
TI  - Pellegrini Stieda disease.

PMID- 21179995
TI  - Diagnostic, interventional and therapeutic procedures of the musculoskeletal
      system applicable in open magnetic resonance units.

PMID- 21179996
TI  - The art and evidence?

PMID- 21179997
TI  - Three-year clinical evaluation of cuspal coverage with combined composite-amalgam
      in endodontically-treated maxillary premolars.
AB  - This clinical study evaluated the clinical performance of cuspal coverage with
      combined composite-amalgam restorations in endodontically-treated maxillary
      premolars over a three-year period. Thirty-six maxillary premolars, each with a
      Class II cavity in 36 patients ranging in age between 28 and 52 years, were
      selected after endodontic treatment. After reduction of the buccal and palatal
      cusps, internal coverage and veneering of the reduced buccal cusp was performed
      with composite. The remaining cavity and reduced palatal cusp were restored with
      high-copper amalgam. The restorations were evaluated at baseline and in one-, two
      and three-year recalls with USPHS criteria. Changes in characteristics of the
      restorations were analyzed with the Cochran Q-test at a significance level of p <
      0.05. Most of the restorations received an overall score of alpha, except two
      restorations, which showed a slight discrepancy at the composite-amalgam
      interface after one year (p > 0.05). Four restorations exhibited slight
      discoloration of the composite veneering after three years (p < 0.05). No
      restoration exhibited fracture after three years. It was concluded that combined
      composite-amalgam cusp coverage of endodontically-treated maxillary premolars
      showed acceptable clinical performance after three years.

PMID- 21179998
TI  - Effect of accelerated aging on the color and opacity of resin cements.
AB  - STATEMENT OF THE PROBLEM: The color stability of resin cements plays a major role
      in the esthetic performance of porcelain laminate veneers. Some dual
      polymerizable resin cements used to bond porcelain laminates were shown to
      undergo color changes during service. Some recently produced cements are
      described as being color stable, but scientific data are not available. PURPOSE:
      The current study evaluated the effect of accelerated aging on the color and
      opacity of resin cements. The hypothesis was that the auto-polymerizing cements
      would show less color and opacity stability. MATERIALS AND METHODS: Forty (0.7 x
      18 mm) feldspathic porcelain disks were prepared and divided into four equal
      groups. The resin cements were bonded to the disks by application of an identical
      load of 2.5 kilograms, and they were polymerized according to the manufacturer's
      instructions. The groups were: Variolink Veneer (light-polymerizing), Variolink
      II (light-polymerizing), Variolink II (dual-polymerizing) and Multilink (auto
      polymerizing). A spectrophotometer was used to measure the following color
      parameters in the CIE L*a*b* color space on a black and white background:
      deltaa*, deltab*, deltaL*, deltaC, deltaH, deltaE and deltaCR (contrast ratio).
      The measurements were performed before and after aging. Paired t- and one-way
      ANOVA tests were used to analyze the data (alpha = .05). RESULTS: None of the
      groups showed significant differences in deltaE before and after aging (p > .05);
      deltaE remained in the range of clinical acceptance (deltaE < 3.3). All of the
      cements became more opaque, while deltaCR (difference in contrast ratio) was
      significantly different (p = .004). The auto-polymerized cement showed an
      increase in opacity. CONCLUSIONS: The studied cements behaved acceptably
      according to deltaE, but they became more opaque after aging. CLINICAL
      IMPLICATIONS: The studied cements can ensure color stability when used to cement
      porcelain laminate veneers, but the change in opacity can affect clinical
      results. Auto polymerizing cements become more opaque with aging; therefore,
      porcelain restorations may lose their match with other teeth.

PMID- 21179999
TI  - Effect of oxalate desensitizer on the durability of resin-bonded interfaces.
AB  - Potassium oxalate desensitizers were previously shown to effectively reduce the
      immediate permeability of resin-bonded dentin. The current study evaluated
      whether the effect of the combined application of oxalate with etch-and-rinse
      adhesives interferes with the durability of resin-dentin bonds when using etch
      and-rinse adhesives. The bond strength of resin-bonded dentin specimens composed
      of two-step or three-step etch-and-rinse adhesives (Single Bond, One-Step and
      Scotchbond Multi-Purpose, respectively) was tested immediately (24 hours) and
      after 12 months of water storage. The adhesives were used either according to the
      manufacturers' instructions (control groups) or after treating acid-etched dentin
      with a potassium oxalate gel (BisBlock, BISCO, Inc). The treatment of dentin with
      potassium oxalate was shown to negatively affect the baseline bond strength of
      resin-bonded dentin specimens, regardless of the adhesive used (p < 0.05). After
      storage, the bond strength of the resin-bonded interfaces was significantly
      reduced for all the tested groups (p < 0.001). Nevertheless, the rate of
      decreasing bond strength was significantly lower for oxalate-treated specimens
      than for the controls (p < 0.05).

PMID- 21180000
TI  - Effect of chlorhexidine application methods on microtensile bond strength to
      dentin in Class I cavities.
AB  - OBJECTIVE: To evaluate the influence of chlorhexidine with different application
      methods on the microtensile bond strength (microTBS) to dentin in Class I
      cavities. METHODS: Flat dentinal surfaces with Class I cavities (4 mm long, 4 mm
      wide, 2 mm deep) in 50 molars were bonded with Adper Single Bond 2 etch-and-rinse
      adhesive system after: 1) Chlorhexidine (CHX) + rinsing + etching; 2) CHX + no
      rinsing + etching; 3) Etching + CHX + rinsing; 4) Etching + CHX + no rinsing; 5)
      Etching only as a control group. Resin composite buildups were constructed with Z
      350 (3M ESPE) using a bulk method and they were polymerized for 40 seconds. For
      each condition, half of the specimens were immediately submitted to microtensile
      bond strength and half of the same group was submitted to 10,000 cycles of
      thermocycling between 5 degrees C and 55 degrees C before testing. The data were
      analyzed using the two-way ANOVA and Student t-test at a 95% significance level.
      RESULTS: Chlorhexidine pretreatment did not affect the bond strength of specimens
      tested at the immediate testing period, regardless of the application method
      used, compared to the control group. However, after 10,000 thermocycles, a
      significant bond strength reduction was found in the control group. In general,
      the chlorhexidine application method did not demonstrate a significant difference
      among the groups treated with chlorhexidine. However, there was a significant
      difference after thermocycling in the groups treated with chlorhexidine before
      etching and no significant difference in the groups treated with chlorhexidine
      after etching. CONCLUSION: Considering the amount of reduction in bond strength
      after thermocycling, the current study showed improved dentin bond strength with
      chlorhexidine when used after etching.

PMID- 21180001
TI  - Effect of surface preparation on bond strength of resin luting cements to dentin.
AB  - This study examined the effects of using two different burs for dentin surface
      preparation on the microtensile bond strength (microTBS) of three resin luting
      cements. Flat, deep dentin surfaces from 45 extracted human third molars were
      divided into three groups (n = 15) according to bur type: (i) diamond bur and
      (ii) tungsten carbide bur. The controls were abraded with #600-grit SiC paper.
      Both burs operated in a high-speed handpiece under water-cooling. Composite
      blocks were luted onto the dentin using one of three cements: RelyX ARC (ARC, 3M
      ESPE), Panavia F2.0 (PF, Kuraray) and RelyX Unicem (UN, 3M ESPE) following the
      manufacturers' instructions. For ARC, the dentin surface was treated with 32%
      phosphoric acid. The bonded specimens were stored at 37 degrees C for 24 hours
      and sectioned into 0.9 x 0.9 mm beams for microTBS testing. The data were
      analyzed using the two-way ANOVA and Student-Newman-Keuls tests. Representative
      fractured beams from each group were prepared for fractographic analysis under
      SEM. Two-way ANOVA revealed that the effects of "dentin surface preparation" and
      "luting cement" were statistically significant (p < 0.001); however, the
      interaction of these two factors was not significant (p > 0.05). ARC showed no
      significant difference in microTBS among the three differently prepared dentin
      surfaces. The microTBS of PF and UN was significantly lower when bonding to
      dentin prepared with a diamond bur (p < 0.05), compared to the control. For
      Panavia F2.0, higher bond strengths were achieved on the dentin surface prepared
      with a tungsten carbide bur. Proper bur selection is essential to optimizing the
      dentin adhesion of self-etch resin luting cements.

PMID- 21180002
TI  - Protective effect of resin coating on the microleakage of Class V restorations
      following treatment with carbamide peroxide in vitro.
AB  - This in vitro study evaluated the effects of a resin coating on the microleakage
      of Class V restorations due to bleaching. One-hundred and sixty Class V cavities
      were randomly restored with one of four different restorative materials (n = 40):
      a compomer (Dyract AP), a conventional glass-ionomer cement (Ketac Molar
      Easymix), a resin modified glass-ionomer cement (Fuji II LC) and a resin
      composite (Filtek Z350). For each kind of material, 40 restorations were divided
      into four subgroups: bleached with resin coating (group BC), bleached without
      resin coating (group B), immersed in artificial saliva with resin coating (group
      SC), immersed in artificial saliva without resin coating (group S). In groups B
      and BC, the specimens were bleached with 10% carbamide peroxide gel for eight
      hours daily, while groups SC and S were stored in artificial saliva instead.
      After 28-day treatment, all the samples were subjected to a dye penetration test
      using the multiple-sectioning technique. In addition, one more test was performed
      to investigate the color difference between the coated and uncoated tooth surface
      after bleaching. There was a statistically significant increase in cervical
      microleakage in the group B specimens of Fuji II LC and Ketac Molar Easymix
      compared to their respective control specimen (group S). These effects on
      microleakage were not found in the bleached specimens with resin coating (group
      BC). There was also no visually-detectable color difference between the coated
      and uncoated tooth surface. In conclusion, resin coating is an effective method
      for avoiding the bleaching-induced microleakage of glass-ionomer cement.

PMID- 21180003
TI  - In vivo and in vitro evaluations of microleakage around Class I amalgam and
      composite restorations.
AB  - This study evaluated and compared microleakage values of in vivo and in vitro
      placed Class I amalgam restorations with or without three different lining
      materials and posterior composite restorations with two dentin bonding agents.
      For the in vivo group, 72 standardized Class I cavities were prepared on the
      occlusal surfaces of molars scheduled for extraction. The test groups (n = 12)
      were: amalgam without lining (A), amalgam with cavity varnish (A+C), amalgam with
      Clearfil SE Bond (A+CSE), amalgam with Clearfil 2V (A+C2V), composite with
      Clearfil SE Bond (C+CSE) and composite with Protect Bond (C+PB). The restored
      teeth were extracted after seven days. The same grouping, materials and
      techniques were used in 72 extracted molars for the in-vitro part of the study.
      The specimens were immersed in basic fuchsin for 24 hours and sectioned.
      Microleakage was examined and scored at 20x magnification. Statistical analyses
      were performed with the Kruskal-Wallis and Mann-Whitney U-tests with the 5% level
      of significance. Overall, the in vivo and in vitro test groups were not different
      from each other. No significant differences in microleakage values were observed
      between the unlined and lined amalgam groups (p > 0.05). However, since lined
      amalgam restorations did not reveal any marginal leakage, the application of an
      adhesive bonding material under the amalgam restorations can be considered. In
      general, cavity varnish was not as effective as adhesive bonding agents in
      preventing microleakage in amalgam restorations. Composite restorations
      demonstrated higher leakage values than amalgam restorations (p < 0.05), except
      for A+C (p > 0.05) in the in vivo group. There was no significant difference
      between the two composite groups for in vitro and in vivo conditions (p > 0.05).

PMID- 21180004
TI  - Degree of conversion of etch-and-rinse and self-etch adhesives light-cured using
      QTH or LED.
AB  - In the current study, the degree of conversion (DC) of bonding agents
      photoactivated using QTH or LED light-curing units (LCUs) was evaluated by
      Fourier Transform infrared spectroscopy with an attenuated total reflectance
      (ATR) device. Four LCUs were evaluated: one QTH (Optilux 501; Demetron Kerr) and
      three LEDs: Radii Cal (SDI), Elipar FreeLight 2 (3M ESPE) and Bluephase (Ivoclar
      Vivadent). Two etch-and-rinse (Scotchbond Multi-Purpose-SBMP and Single Bond 2
      SB2) and two self-etch adhesives (Clearfil SE Bond-CSE, and Clearfil S3 Bond-CS3)
      were tested. For SBMP and CSE, the primer was not used. The irradiance and
      spectral emission of the LCUs were obtained with a radiometer and spectrometer.
      The materials were placed onto the ATR cell as thin films, the solvent was
      evaporated (when necessary) and photoactivation was carried out for 20 seconds.
      The DC (%) was evaluated after five minutes (n = 5). The data were statistically
      analyzed (p < 0.05). The irradiance for Optilux, Radii, FreeLight 2 and Bluephase
      was 760, 600, 1000 and 1100 mW.cm(-2), respectively. The wavelength of emission
      for Optilux was between 375 and 520 nm (peak at 496 nm), while for Radii, it was
      between 420 and 520 nm (peak at 467 nm). Freelight 2 presented an emission
      spectrum between 415 and 520 nm, and for Bluephase, it was between 410 and 530
      nm, both having a peak at 454 nm. SB2 generally showed higher DC compared with
      the other bonding agents. When cured using the QTH unit, the DC results were SB2
      = CS3 > CSE > SBMP; for all LEDs, the DC results showed SB2 > CSE > SBMP > CS3.
      For SB2, the highest DC was observed when the material was cured with Radii,
      while there were no significant differences among the other LCUs. CSE and CS3
      showed higher DC when cured using the QTH unit, but similar results were observed
      among the LEDs. For SBMP, no significant differences among the LCUs were
      detected. In conclusion, the combination bonding agent vs curing unit had a
      significant effect on DC, mainly for the self-etch adhesives.

PMID- 21180005
TI  - Bond strength comparison of amalgam repair protocols using resin composite in
      situations with and without dentin exposure.
AB  - The replacement of defective amalgam restorations leads to loss of tooth material
      and weakens the tooth, creating an increased risk of cusp fracture. The repair of
      such defects is a minimal intervention technique. The current study compared the
      repair bond strengths of a resin composite to amalgam and an amalgam-dentin
      complex after various surface conditioning methods. The specimens (N = 50)
      consisted of sound human canines with cylindrical preparations (diameter: 2.3 mm,
      depth: 3 mm) with amalgam-dentin complex (N = 30, n = 10/per group) and two
      groups with amalgam only (N = 20, n = 10/per group). The teeth were embedded in
      auto-polymerized polymethylmethacrylate (PMMA). The preparations were filled with
      non-Gamma 2 amalgam. The enamel was removed to expose dentin. The specimens with
      the amalgam-dentin complex were randomly assigned to one of the following
      conditioning methods: Group 1: Silicacoating amalgam, etching dentin, silane
      application on amalgam, primer/bonding on dentin, opaquer on amalgam, resin
      composite on both; Group 2: Etching dentin, silicacoating amalgam, silane
      application on amalgam, primer/bonding on dentin, opaquer on amalgam, resin
      composite on both and Group 3: Etching dentin, primer/bonding on dentin, opaquer,
      resin composite. The specimens with only amalgam were assigned to one of the
      following conditioning methods: Group 4: Silicacoating, silane application,
      opaquer, resin composite and Group 5: Opaquer, resin composite. For the two
      control groups, where no dentin was involved (Groups 4 and 5), bonding was
      achieved only on amalgam and Group 5 had no conditioning. The specimens were kept
      in water at 37 degrees C for five weeks before bond strength (MPa +/- SD) testing
      (Universal Testing Machine). After debonding, the failure types were analyzed.
      The results were significantly affected by the surface conditioning method
      (ANOVA). Only dentin conditioning (Group 3) showed the highest bond strength
      (39.9 +/- 14). The unconditioned control group (Group 5) showed the least
      favorable results (1.4 +/- 0.5). Multiple comparisons (Tukey-Kramer adjustment)
      showed that the mean values of Group 1 (34.1 +/- 11.4), 3 (39.9 +/- 14) and 4
      (35.5 +/- 4) were not significantly different (p > 0.05), but between Groups 2
      (22.8 +/- 6.6) and 3 (39.9 +/- 14), significant differences were observed (p =
      0.0027). For reliable repair of amalgam restorations, including dentin fractures,
      the amalgam surface should first be silica coated, then the dentin/enamel should
      be etched, washed and rinsed thoroughly. Finally, the amalgam should be silanized
      and primer/bonding applied onto the dentin.

PMID- 21180006
TI  - Effect of pre-heated composites and flowable liners on Class II gingival margin
      gap formation.
AB  - PURPOSE: To evaluate the effect of preheated composites (PHC) and flowable liners
      (FL) on the gingival margin gap formation of Class II composite restorations
      compared to the placement of room temperature composites (RTC). MATERIALS AND
      METHODS: Class II composite restorations were prepared on 40 extracted mandibular
      third molars, with the gingival margin located 1 mm below the CEJ in dentin.
      Optibond FL (Kerr), microhybrid Filtek Z-250 (3M ESPE) and Flow-It (Jeneric
      Pentron) were used to evaluate five study groups: 1) PHC, 130 degrees F/54.4
      degrees C; 2) PHC, 155 degrees F/68.3 degrees C; 3) FL cured prior to the first
      increment composite; 4) FL cured simultaneously with the first increment
      composite and 5) RTC (Control). Impressions were taken with quick set polyvinyl
      siloxane impression material, and epoxy resin replicas were evaluated under SEM
      (200x). Gingival margin adaptation was quantitatively evaluated in terms of
      percentage of gap formation according to a modified ordinal scoring criteria. All
      margins were evaluated twice for reliability assessment. A non-parametric Kruskal
      Wallis test was used to determine whether significant differences in gap
      formation existed among the study groups. RESULTS: A high level of agreement was
      observed between duplicate measurements of the percentage of gap formation (intra
      class correlation = 0.956, p < 0.0001). There was no evidence of a difference
      among groups defined by placement technique (p = 0.82). Overall, the mean gap
      percentage for the 40 margins evaluated was 6.3 (Median = 1.1; SD = 14.8).
      CONCLUSIONS: Gingival margin adaptation was not improved relative to the control
      by any of the placement techniques tested. No significant differences in gap
      formation were found among the study groups. A high degree of intra-examiner
      reliability was confirmed.

PMID- 21180007
TI  - Influence of prolonged light-curing time on the shear bonding strength of resin
      to bleached enamel.
AB  - This study evaluated the effect of prolonged light-curing time using a light
      emitting diode unit (LED) on the shear bond strength of a resin composite to
      enamel immediately after bleaching. The enamel surfaces of human molars were
      divided into four groups: one control and three bleaching groups. One bleaching
      group (CP) was exposed to a 10% carbamide peroxide bleaching agent and bonded
      after 24 hours. The other two bleaching groups (HP) were bleached with a 38%
      hydrogen peroxide bleaching agent, then bonded either within one hour (HPA) or
      after 24 hours (HPB). All groups were subdivided into two subgroups and cured for
      two different times (20 or 40 seconds) with an LED unit. Shear bond strength
      (SBS) was tested with a universal-testing machine and the data were analyzed by
      ANOVA and post-hoc tests. Scanning electron micrographs of representative
      specimens were taken. A significant difference was seen between the control and
      HPA groups for both curing times (p = 0.000). However, neither the CP nor HPB
      groups showed any significant differences compared with the control groups (p >
      0.05). Two-way ANOVA showed that a significant effect of the curing time factor
      was recorded for all groups (p = 0.000). Prolonged curing time, using an LED unit
      with a light intensity of 500 mW/cm2, increased resin-enamel bonding strengths
      for the control and bleached groups when bonding was performed after 24 hours of
      immersion in deionized water. However, the SBS was still compromised when bonding
      was performed immediately to enamel bleached with 38% HP.

PMID- 21180008
TI  - The effect of oxalate desensitizers on the microleakage of resin composite
      restorations bonded by etch and rinse adhesive systems.
AB  - This in vitro study evaluated the effect of an oxalate desensitizer (OX) on the
      marginal microleakage of resin composite restorations bonded by two three-step
      and two two-step etch and rinse adhesives. Class V cavities were prepared on the
      buccal surfaces of 126 extracted premolars at the cementoenamel junction and
      randomly divided into nine groups of 14 each. In the control groups (1-4), four
      adhesives were applied, respectively, including Adper Scotchbond Multi-Purpose
      (SBMP), Optibond FL (OBFL), One-Step Plus (OS) and Excite (EX). In the
      experimental groups (5-8), the same adhesives, in combination with OX (BisBlock),
      were applied. And, in one group, OX was applied without any adhesive, as the
      negative control group (9). All the groups were restored with a resin composite.
      After 24 hours of storage in distilled water and thermocycling, the samples were
      placed in 1% methylene blue dye solution. The dye penetration was evaluated using
      a stereomicroscope. The data were analyzed using non-parametric tests. The OX
      application, in combination with OBFL and EX, resulted in significantly
      increasing microleakage at the gingival margins (p < 0.05), while it had no
      effect on OS and SBMP (p > 0.05). At the occlusal margins, no significant
      difference in microleakage was observed after OX application for each of four
      adhesives (p > 0.05).

PMID- 21180010
TI  - The view from Austin. Vascular lesions.

PMID- 21180009
TI  - Adhesive quality of self-adhesive and conventional adhesive resin cement to Y-TZP
      ceramic before and after aging conditions.
AB  - PURPOSE: This study evaluated the adhesive quality of simplified self-adhesive
      and conventional resin cements to Y-TZP in dry and aged conditions. METHODS: Y
      TZP ceramic blocks (N = 192) (5 x 5 x 2 mm) were embedded in acrylic resin and
      randomly divided into two groups, based on surface conditioning: 96% isopropanol
      or chairside tribochemical silica coating and silanization. Conditioned ceramics
      were divided into four groups to receive the resin cements (Panavia F 2.0,
      Variolink II, RelyX U100 and Maxcem). After 24 hours, half of the specimens (n =
      12) from each group were submitted to shear bond strength testing (0.5
      mm/minute). The remaining specimens were tested after 90 days of water storage at
      37 degrees C and thermocycling (12,000x, 5 degrees C-55 degrees C). Failure types
      were then assessed. The data were analyzed using three-way ANOVA and the Tukey's
      test (alpha = 0.05). RESULTS: Significant effects of ceramic conditioning, cement
      type and storage conditions were observed (p < 0.0001). The groups cleaned using
      alcohol only showed low bond strength values in dry conditions and the bond
      strength was reduced dramatically after aging. Groups conditioned using silica
      coating and silanization showed higher bond strengths both in dry and aged
      conditions. A high number of specimens failed prematurely prior to testing when
      they were cleaned using 96% isopropanol. CONCLUSION: Overall, silica coating and
      silanization showed higher, stable bond strengths with and without aging. The
      durability of resin-ceramic adhesion varied, depending on the adhesive cement
      type.

PMID- 21180011
TI  - Influential teachers in our educational experience.

PMID- 21180012
TI  - Moving from cottage industry to a corporate organization.

PMID- 21180013
TI  - Vascular lesions of the maxillofacial region: a case report and review of the
      literature.
AB  - There is frequently lack of understanding and apprehension among dental
      practitioners treating patients with vascular lesions of the oral and
      maxillofacial region. Arteriovenous malformations are rare lesions which can
      easily be misdiagnosed yet produce the very dramatic clinical presentation of
      severe life threatening oral bleeding. Much of this apprehension likely stems
      from a lack of understanding of these anomalies, including lesion behavior/
      characteristics, clinical work-up, and treatment paradigms. A comprehensive, in
      depth review of the full spectrum of vascular lesions of the maxillofacial
      complex is beyond the scope of this review. The purpose of this article is to
      provide a comprehensive review of the diagnosis, treatment, and risks associated
      with these complex vascular anomalies and provide a case report. In 1982,
      Mulliken and Glowacki published a landmark article proposing characterization of
      vascular defects based on biologic and pathologic differences. Their work
      differentiated between two major categories of vascular lesions: hemangiomas and
      vascular malformations. Different categories, names, and treatment options have
      been advocated over the years with multiple outcomes. They can occur in various
      areas throughout the body, with 60 percent being located in the head and neck.
      The true mechanism of pathogenesis of vascular anomalies is still unclear.
      Embolization and surgery is often combined for extended cases to improve their
      facial contour and oral function. We present the case of a 29-year-old female
      that is 36 weeks pregnant and presented to University Hospital after having
      significant bleeding from her oral cavity. She was found to have a gingival
      lesion associated with a radiolucency in the right posterior mandible. During her
      stay she had an episode of acute bleeding that required an emergent exploration,
      embolization, and resection secondary to an Arteriovenous Malformation associated
      with the Inferior Alveolar Artery. We will discuss the presentation, treatment
      provided, and outcome of this patient. We will also cover the diverse group of
      congenital vascular malformations, and their pathologic, clinical, and radiologic
      diagnosis and management.

PMID- 21180014
TI  - Oral health care for the pregnant patient.
AB  - Pregnancy is a unique time in a woman's life, accompanied by a variety of
      physiologic, anatomic, and hormonal changes that can affect how oral health care
      is provided. However, these patients are not medically compromised and should not
      be denied dental treatment simply because they are pregnant. This article
      discusses the normal changes associated with pregnancy, general considerations in
      the care of pregnant patients, and possible dental complications of pregnancy and
      their management.

PMID- 21180015
TI  - Dentists and politics.

PMID- 21180016
TI  - 2011 legislative landscape.

PMID- 21180017
TI  - A view from the Capitol.

PMID- 21180018
TI  - Delivering dental care to Texas' at-risk children: TDA members are heeding the
      call.

PMID- 21180019
TI  - Mandatory dental exams for school children ... healthy mouth and healthy child.

PMID- 21180020
TI  - The national legislative picture.

PMID- 21180021
TI  - The State Board of Dental Examiners update.

PMID- 21180022
TI  - Advocacy for the future: TDA 2014.

PMID- 21180023
TI  - The comprehensive new patient experience: from "thank you for calling" to "when
      can we start?".

PMID- 21180024
TI  - How much with shipping?

PMID- 21180025
TI  - Value for your profession. Three quick fixes for broken appointments.

PMID- 21180026
TI  - Case of the month. Periapical cemento-osseous dysplasia.

PMID- 21180027
TI  - Bisoprolol and heart failure: new frontiers.
AB  - Clinical trials have consistently shown the benefits of beta-blocker treatment in
      patients with chronic heart failure (HF). As a result, bisoprolol, carvedilol,
      and metoprolol succinate are now indicated for the treatment of all patients with
      chronic HF who do not have major contraindications. In the Cardiac Insufficiency
      Bisoprolol Study II (CIBIS-II), all-cause mortality and sudden death were reduced
      in patients treated with bisoprolol when compared with those on placebo (11.8%
      vs. 17.3%; p < 0.0001 and 3.6% vs. 6.3%, p < 0.002; respectively) regardless of
      age, New York Heart Association (NYHA) functional class and co-morbidities. More
      recently, CIBIS-III has shown similar efficacy and safety of the initiation of HF
      treatment with either bisoprolol or enalapril, with a tendency to a survival
      advantage with bisoprolol. Nowadays, the role of bisoprolol, as well as that of
      carvedilol and metoprolol succinate, in HF treatment is firmly established and
      research is mainly focused on implementation of treatment and better dosing. This
      article will summarize evidence for the efficacy of bisoprolol in the treatment
      of HF.

PMID- 21180028
TI  - Central aortic blood pressure assessment and cardiovascular risk.
AB  - Peripheral brachial blood pressure measurements may not provide an accurate
      representation of degenerative changes that characterize cardiovascular disease.
      Evidence is mounting that antihypertensive treatment strategies with apparently
      similar effects on brachial blood pressure may have different effects on central
      aortic pressure, which in turn may lead to overestimation or underestimation of
      therapeutic efficacy. The relative importance of central and brachial blood
      pressure for predicting cardiovascular risk and clinical outcomes has been
      examined in several clinical studies. These studies have reported that a large
      proportion of individuals considered to have normal blood pressure values based
      on brachial systolic pressures had high-normal blood pressure based on central
      aortic pressure measurements. As additional evidence suggesting the superiority
      of central aortic pressure over peripheral assessments becomes more abundant,
      measurement of central aortic pressure may be the next important advancement in
      the management of hypertension.

PMID- 21180029
TI  - Percuteneous mitral balloon valvuloplasty in patients with post surgical mitral
      restenosis: result of 70 cases.
AB  - OBJECTIVE: To evaluate the immediate results of balloon mitral valvulplasty in
      mitral restenosis patients with previous surgical mitral commissurotomy. METHODS:
      Percuteneous balloon mitral valvuloplasty (BMV) was done in 145 cases of which
      70patients had the history of previous surgical commissurotomy (Group I) and 75
      patients were the new cases for the BMV (Group II). RESULTS: In group I the age
      range was 35-65 years. In group I the duration of surgical commissurotomy (SC)
      was of 2-18 years past. In this group the result of balloon mitral valvuloplasty
      (BMV) was successful in 69 cases. Mitral valve area (MVA) before the procedure
      was 0.5-0.9 sq cm with mean 0.7 +/- 0.2 sq cm. Following procedure the MVA was
      1.2-2.0 cm2 with a mean of 1.6 +/- 0.4 cm2. Mean gradient across mitral valve
      (MV) before the procedure was 15-25 mm of Hg with a mean 20 +/- 5 mm of Hg and
      after the procedure was 3-5 mm Hg with a mean of 4 +/- 1 mm Hg. In Group I, MVA >
      1.8 cm2 was achieved in 25 cases & > 1.2-1.8 cm2 in 44 cases. Mitral
      regurgitation > or = grade 1 occurred in 8 cases (compared to previous
      echocardiography). In group II the age range was between 35-60 years. The result
      of BMV was successful in 74 cases. MVA before the procedure was 0.4-1.2 cm2 with
      a mean of 0.8 +/- 0.4 cm2. Following the procedure MVA was 1.3-2.1 cm2 with a
      mean of 1.7 +/- 0.4 cm2. Mean gradient across the mitral valve before the
      procedure was 15-29 mm of Hg with a mean of 22 +/- 7 mm of Hg. Mean gradient
      across the mitral valve after the procedure was 2-4 mm of Hg with a mean of 3 +/-
      1 mm of Hg. MVA more than 1.8 cm2 was achieved in 29 cases and between 1.3-1.8 in
      45 cases. CONCLUSION: BMVin patients with mitral restenosis following Surgical
      mitral commissurtomy can be performed with almost similar success rate like that
      of BMV for the first time with low risk of major cardiac complication.

PMID- 21180030
TI  - Diagnosis and management of failed thrombolytic therapy for acute myocardial
      infarction.
AB  - Thrombolytic therapy continues to remain the most frequently adopted treatment
      for patients of acute myocardial infarction. Despite our best efforts,
      thrombolytic therapy is not uniformly successful. In this review we have
      discussed the incidence, diagnosis and management of failed thrombolysis. The
      different meta-analysis of rescue angioplasty and various nuances of this
      treatment are presented.

PMID- 21180031
TI  - Myocardial perfusion single photon emission computed tomography in asymptomatic
      diabetics.
AB  - BACKGROUND: Coronary artery disease (CAD) is the most important cause of
      mortality in diabetic patients. Diabetes mellitus (DM) due to autonomic
      neuropathy leads to asymptomatic CAD. Hence, it is important to screen the
      patients with DM for CAD. AIM: To study the prevalence of asymptomatic CAD by
      Myocardial Perfuision SPECT (Single Photon Emission Computed Tomography) (MPS) in
      diabetics. METHODS: This prospective study included 88 asymptomatic patients (58
      males and 30 females) of Type 2 DM of more than 5 years duration in the age group
      of 40-65 years. Risk factors like hypertension, dyslipidemia, smoking, family
      history of CAD and Body Mass Index > or = 25 kg/sq.m were assessed. All these
      patients underwent MPS study as two day standard protocol. Thirty eight patients
      underwent invasive Coronary Angiography (CAG) and stenosis greater than 50% was
      considered significant. RESULTS: Abnormal perfusion was detected in 38 (43%)
      diabetics and 4 (11%) controls. A total of 81 perfusion defects were identified
      (19 fired and 62 reversible). CAG showed significant coronary stenosis in 26
      (68.4%), insignificant in 8 (21%) and no stenosis in 4 (10.6%) patients. A total
      of 114 coronaries were analysed, significant stenosis in 67 (58.8%) coronaries,
      21 (18.4%) had insignificant lesions and 26(22.8%) were normal. In comparison to
      CAG, MPS had sensitivity of 86.6% and specificity of 51%. CONCLUSION: The
      Myocardial Perfusion SPECT is a sensitive diagnostic tool to identify ischemia in
      asymptomatic diabetics. MPS can be used as screening test for risk
      stratification. It has a prognostic value in predicting the outcome of CAD and
      can be useful for long-term follow up too.

PMID- 21180032
TI  - NT-pro-BNP levels as a marker of success of percutaneous transvenous mitral
      commissurotomy.
AB  - BACKGROUND: Brain natriureticpeptide (BNP) levels are elevated in patients with
      rheumatic mitral stenosis (MS) and decrease after a successful percutaneous
      transvenous mitral commissurotomy (PTMC). METHODS: In 37 consecutive patients of
      symptomatic MS (mean age 30 +/- 8.6 years) NTpro BNP levels were determined pre
      and 24-hours post PTMC. We seek to determine whether NT-pro-BNP levels be used as
      a marker of success of PTMC. RESULTS: PTMC was successful orpartial successful in
      33 (89 %) cases. The mean NT-pro- BNP levels decreasedfrom 771 +/- 456 pg/ml to
      700 +/- 595 pg/ml (p < 0.05) following PTMC. The mean NT-pro-BNP levels decreased
      by 20.6% in patients with a successful PTMC and decreased by 10.8% in patients
      with a partially successful PTMC, while the levels increased by 33.4% in patients
      with an unsuccessful procedure. Patients with associated aortic regurgitation
      failed to show a decline in NT-pro-BNP levels despite a successful procedure.
      CONCLUSION: NT-pro-BNP levels fall significantly after a successful PTMC, and a
      significant decrease in levels is a good marker of success of PTMC. It may not
      decrease in patients with associated aortic regurgitation despite a successfiul
      PTMC.

PMID- 21180033
TI  - Importance of ischaemic time as a predictor of LV systolic function in Indians.
AB  - OBJECTIVE: Sucessful reperfusion therapy in AMI improves LV systolic function.
      Success in thrombolytic therapy is directly related to the ischaemic time. Our
      aim in the present study was to observe the importance of ischaemic time as a
      predictor of left ventricular systolic function in patients undergoing PPCI. In
      addition, the contribution of presentation delay in determining the ischaemic
      time in the Indian scenario was also observed. MATERIALS & METHODS: The present
      pilot study was carried out on 48 Indian patients (Male-40) of STEMI (Killip
      class I & II) undergoing primary PCI in last 2 yrs. Suggestive chest pain, ECG
      evidence of STEMI coming within 12 hrs were the inclusion criteria. Patients
      coming after 12 hours without ongoing chest pain, Killip class III & IV, the
      patients who were thrombolysed outside and the patients with prior PCland/or CABG
      were excluded from the study. Cardiac echodoppler study was done in every patient
      during followup at one month.Every patient received pre and peri procedural
      abciximab infusion and thrombosuction was done in all before deployment of BMS
      during the transfemoral primary PCI. RESULTS: Data analysis revealed mean age was
      57.6 yrs, male preponderance (80%),diabetes (35%),hypertension (61%), Smoking
      (61%), average total ischaemic time 7.6 +/- 3.78 hours, average presentation
      delay 6.26 +/- 3.77 hrs, average door to balloon time 60 +/- 14 mins, SVD (69%),
      LAD involvement(60%). Multivariate regression analysis without considering any
      other factor showed predicted LV Systolic function one month post PPCI to be
      74.08%. Mean LVEF: 58.2%. Most interesting observation is 0.63% reduction of
      predicted LVEF for each hour increment of ischaemic time. Also LAD occlusion is
      associated with 4.91% reduction of predicted LVEF compared to other vessel(s)
      involvement. All the 48 patients who underwent PPCI not only survived but also
      had good LV Systolic function one month post PPCI. CONCLUSION: Ischaemic time is
      an important predictor of LV Systolic function even after PPCI. lncrease in
      ischaemic time by one hour reduces predicted LVEF by 0.63%.Presentation delay is
      mostly responsible for total ischaemic time in India.

PMID- 21180034
TI  - Tansplantation of autologous bone marrow derived mesenchymal stem cells trans
      epicardially in patients undergoing coronary bypass surgery.
AB  - BACKGROUND: Myocardial Infarction (MI) hampers cardiac performance by ventricular
      remodeling which is a major cause of heart failure or death. Conventional drug
      therapies like beta blockers, angiotensin-converting enzyme may delay remodeling
      but there is no single therapeutic regimen available that can prevent or reverse
      the process of myocardial injury. Interventional therapies and surgical
      procedures improve or normalize coronary blood flow greatly. Experimental data
      suggests that bone marrow derived Mesenchymal Stem Cells (MSCs) may contribute to
      the healing of Myocardial infarction. We present our findings on the use of bone
      marrow derived MSCs for Myocardial Infarction wherein the cells were injected in
      and around the infarct region epicardially during coronary bypass surgery.
      METHODS & MATERIALS: 31 patients selected to undergo Coronary Artery Bypass Graft
      (CABG) as a treatment option for myocardial infarction formed the subject matter
      of our study. One patient withdrew consent before receiving our therapy and was
      excluded from the study. 15 patients (all men, average age 57) formed the test
      arm who underwent CABG plus Bone Marrow Mesenchymal Stem Cells (BMMSCs)
      transplantation whereas another 15 patients underwent conventional CABG only (14
      men and 1 woman, mean age 57) served as the control arm. The cell transplantation
      consisted of injecting BMMSCs in the border zone of the clearly visible infarcted
      area transepicardially. The absolute number of MSCs injected ranged between 3
      million and 26 million cells. RESULTS: The data for change from baseline in the
      area of infarct was collected at 3 months and 6 months during the study and
      analyzed using paired t-tests. The mean percentage perfusion improvement from
      baseline in the area of infarct supplied by the Left Anterior Descending Artery
      (LAD) was higher in the cases (35.8%) as compared to the controls (11.3%) at 3
      months post treatment (p value < 0.05). There were three cases of arrhythmia, and
      none of the adverse events recorded were due to the investigational product.
      Improvement in the ejection fraction was similar in the cases and controls.
      CONCLUSIONS: This study demonstrates that trans-epicardial uses of mesenchymal
      stem cells are very safe and feasible. Correction of perfusion defect is very
      encouraging. Larger studies using higher doses of mesenchymal stem cells may
      bring about better understanding.

PMID- 21180035
TI  - First orally active DRI Aliskiren--a new prospect in management of hypertension
      and beyond.
AB  - Hypertension is a major public health problem and leading cause for diseases
      involving cardiovascular & renal system. It is fourth largest contributor for
      premature deaths in developed countries and seventh largest in developing world.
      The major pharmacological strategies currently utilized for hypertension
      management include volume control with diuretics, suppression of central and
      peripheral sympathetic nervous system activity, vasodilatation with ion channel
      manipulation and blockade of renin-angiotensin-aldosterone system. Activation of
      the renin-angiotensin-aldosterone system in the pathogenesis of cardiovascular
      diseases and renal disease is well established. It also has been established that
      inhibition of renin-angiotensin-aldosterone system, is an effective way to
      intervene with pathogenesis of these disorders. Therapies like beta blockers,
      renin inhibitors, angiotensin converting enzyme inhibitors, angiotensin receptor
      blockers and aldosterone inhibitors, that inhibit renin-angiotensin-aldosterone
      system have proven to be highly successful for treatment of hypertension &
      related cardiovascular diseases. Renin inhibitors block the renin-angiotensin
      aldosterone system at its origin, and thus offer a new approach to
      pharmacotherapy of Hypertension. Aliskiren is the first in a new class of orally
      active, non-peptide, low molecular weight direct renin inhibitor available for
      clinical use and potential new approach to the blockade of the renin-angiotensin
      aldosterone system. Studies in humans demonstrate to an effectual blood Pressure
      lowering effect of aliskiren with placebo like tolerability, when used as
      monotherapy or in combination with other agents and has the potential to be
      useful in this wide spectrum of conditions

PMID- 21180036
TI  - Soluble levels of cell adhesion molecules (CAMs) in coronary artery disease.
AB  - AIMS: To analyze soluble levels ofcell adhesion molecules (CAM) such as
      Intercellular CAM (ICAM), vascular CAM (VCAM-1), platelet endothelial CAM (PECAM
      1), Endothelial (E)-selectin, and Platelet (P)-selectin in coronary artery
      disease patients and correlate with degree of severity of the disease. METHODS:
      Study population included patients who suffered myocardial infarction at
      presentation (N=49) and those with unstable angina (N=79) and stable angina
      (N=14). Soluble levels of CAMs were measured by ELISA. RESULTS: At acute event in
      AMI patients, there was significant rise of soluble (s) E-selectin (4.5 fold, P =
      0.001), sVCAM-1 (65.6%, p = 0.001), sPECAM-1 (46.2%, p = 0.02), sP-selectin
      (42.7%, p = 0.001) and sICAM-1 (20.1%, p = 0.003) as compared to controls. In
      unstable angina group as compared to AMI there was significant decrease in the
      levels observed in, sE-selectin (62.7%, p = 0.001), sPECAM-1 (47.5%, p = 0.001)
      as well as sVCAM-1 (17.9%, p = 0.04) and insignificant decrease with respect to
      sICAM-1 and no change with respect to sP-selectin levels. Stable angina group as
      compared to unstable angina group demonstrated no significant difference in sCAMs
      and the trend with AMI group was similar to that seen between unstable angina and
      AMI group. Significantly elevated levels of sE-selectin, sVCAM-1 and sPECAM-1 at
      acute event suggest them to be causal molecules as well as markers of plaque
      destabilization. Levels of sP-selectin in stable angina were similar to that
      observed in AMI and unstable angina groups suggesting elevated platelet
      activation in stable angina as well.

PMID- 21180037
TI  - Evaluation of maternal myocardial performance during normal pregnancy and post
      partum.
AB  - AIMS: Little information exists about the use of noninvasive methods to
      characterized left ventricular mechanical adaptation during normal pregnancy. The
      aim of this study was to evaluate left ventricular performance during normal
      pregnancy and study the effect of maternal factors. METHODS AND RESULTS: The
      study was conducted at Govt. Medical College and New Civil Hospital, Surat
      between February 2006 to March 2008. M-mode and Doppler echocardiography was
      performed in 31 normal pregnant women at 30-40 weeks and 8-12 weeks postpartum.
      Heart rate, stroke volume, cardiac output and left ventricular mass increased
      significantly, while total vascular resistance decreased significantly during
      last trimester of pregnancy. Left ventricular contractility indices (percentage
      ejection fraction and fraction shortening) were within normal limit during
      pregnancy but fractional shortening was significantly higher post-partum than in
      the last trimester of pregnancy (p < 0.05). Maternal age was related to the
      transmitral peak velocity of early filling (E, p = 0.001) and the E to A ratio (p
      < 0.001), while height was related to heart rate (p < 0.001), stroke volume (p =
      0.003), cardiac output (p < 0.001) and left ventricular mass (<0.005).
      CONCLUSION: This study express that along with gestation, maternal anthropometric
      profile may affect cardiac performance. Systolic performance was better in tall
      individuals and diastolic performance was better in younger individuals.

PMID- 21180038
TI  - Takotsubo cardiomyopathy.
AB  - Takotsubo cardiomyopathy is a cardiac dysfunction characterized by transient
      segmented ballooning of the left ventricle, usually the apical region. It mainly
      affects postmenopausal women and represents 1 to 2% of all cases of suspected
      myocardial infarction. Clinical presentation is similar to that of an acute
      coronary syndrome, with chest pain and dyspnea as the main symptoms. Cardiac
      biomarkers and ECG are unable to differentiate Takotsubo from myocardial
      infarction. The diagnosis is suggested by the coexistence ofabnormal regional
      left ventricle kinetics, often severe, together with the absence of significant
      coronary disease. MRI imaging may be useful to confirm the diagnosis. Management
      mainly focuses on stabilising the patient's hemodynamics during the acute phase.
      Prognosis is usually excellent, and complete recovery of cardiac function is the
      norm. We report five cases of Takotsubo cardiomyopathy recently seen in our
      institution and review the literature.

PMID- 21180039
TI  - Cardiac manifestation of lymphoma.

PMID- 21180040
TI  - Early coronary artery aneurysm formation after drug-eluting stent implantation: a
      case report.

PMID- 21180041
TI  - Coronary artery-cameral fistula under cardiovascular image.
AB  - Coronary cameralfistula, a congenital uncommon clinical entity, is a
      communication between the coronary artery or arteries and the chambers of the
      heart usually encountered occasionally during detailed Echocardiography or
      Cardiac intervention. The functional significance and management of these
      fistulas remain uncertain.

PMID- 21180042
TI  - Echo of the month. Likely diagnosis: glycogen storage disorder, e.g., pompe's
      disease.

PMID- 21180043
TI  - The case of disappearing coronary stenosis.

PMID- 21180044
TI  - Left atrial extension of lung malignancy with ECG changes resembling STEMI.
AB  - Lung malignancy extending into left atrium is seen very infrequently. We had a
      patient with a fast growing symptomatic lung mass and electrocardiogram showing
      persistent coving ST elevation without any biomarker change. Transthoracic
      echocardiography showed a large left atrial mass which was fixed to the free
      walls and extended into the appendage. There was also a large lung mass that was
      compressing the heart from its lateral aspect. CT-scan of chest corroborated the
      lung mass & CT-guided FNAC showed small cell carcinoma.

PMID- 21180045
TI  - Catecholaminergic polymorphic ventricular tachycardia with associated sinus node
      dysfunction.
AB  - An 11-year-old Nepalese male child presented with history of recurrent abrupt
      episodes of syncope for the last one year. There was no family history of sudden
      death at a young age in his family. ECG at base-line revealed an isorhythmic AV
      dissociation with a heart rate of 50 bpm and a normal QTc. Echocardiography of
      the heart was normal. His 24 hour holter study revealed frequent VPC's and
      episodes of polymorphic ventricular tachycardia. Exercise stress test provoked a
      polymorphic VT. On EP study, sinus node recovery time (SNRT) was prolonged and
      ventricular tachycardia (VT) was induced on Isoproterenol infusion. He was
      treated with a permanent pacemaker and beta-blocker.

PMID- 21180046
TI  - Percutaneous balloon pericardiotomy in a patient with end stage renal disease
      with recurrent pericardial effusion & pericardial tamponade.
AB  - A case report of 37-year-old female with end stage renal disease presented with
      recurrent pericardial effusion and cardiac tamponade, who underwent percutaneous
      balloon pericardiotomy using an Inoue balloon dilating catheter, to create a non
      surgical pericardial window. The procedure of non-surgical pericardial window is
      safe and effective alternative to conventional more invasive surgical pericardial
      window. It is concluded that percutaneous balloon pericardiotomy is helpful in
      the management of massive pericardial effusions particularly in patients with
      chronic renal failure and poor clinical condition.

PMID- 21180047
TI  - Primary PCI for acute anterior wall MI with pulmonary edema and left anterior
      descending artery ostial stenosis.

PMID- 21180048
TI  - Evaluating status of thrombolysis in pulmonary embolism.

PMID- 21180049
TI  - [Drinking behavior and c-fos expression induced by chemical or electrical
      stimulation of SFO in rat brain].
AB  - AIM: To compare the drinking behavior and c-fos expression induced by chemical or
      electrical stimulation of subfornical organ (SFO) in rat brain. METHODS: L
      glutamic acid microinjection and constant electrical current were used as
      chemical and electrical stimulation of SFO, respectively. The water intake over 1
      h was recorded and Fos expression was examined immunohistochemically. RESULTS: A
      similar volume of water intake and Fos expression pattern were induced by both
      methods of stimulation of SFO. These include 11 forebrain areas (organum
      vasculosum of the lamina terminalis, median preoptic nucleus, hypothalamic
      paraventricular nucleus, supraoptic nucleus and lateral hypothalamic area,
      paraventricular nucleus, reunions nucleus and central medial nucleus of thalamus,
      bed nucleus of the stria terminalis, perifornical dorsal area and substantia
      innominata) and 4 areas of hindbrain (area postrema, nucleus solitary tract,
      lateral parabrachial nucleus and dorsal raphe nucleus). CONCLUSION: The drinking
      behavior and Fos expression in brain induced by SFO stimulation are the results
      of activation of the neuronal bodies in SFO.

PMID- 21180050
TI  - [Effect of tetramethylpyrazine on voltage-dependent channels in aortic smooth
      muscle of rat].

PMID- 21180051
TI  - [Effects of anoxia/reoxygenation on Fos and Jun expression and apoptosis in
      cultured rat hippocampal neurons].
AB  - AIM: To investigate the effects of anoxia/reoxygenation on Fos and Jun expression
      and apoptosis in cultured rat hippocampal neurons. METHODS: The hippocampal
      neurons cultured for 12 d were exposed to anoxia environment (90% N2 + 10% CO2)
      for 4 h and then reoxygenated for 24 h and 72 h. The neurons were
      immunocytochemically stained using the antiserum against Fos and Jun, and the
      apoptosis were detected by using the terminal deoxynucleotidyl transferase
      mediated biotinylated deoxyuridine triphosphate nickel end labeling (TUNEL)
      method and flow cytometric analysis. RESULTS: The percentage of Fos and Jun
      positive neurons and apoptosis neurons in cultured hippocampal neurons after
      anoxia/reoxygenation increased than those in control. CONCLUSION: The occurrence
      of neurons apoptosis is related to the increase in Fos and Jun expression in
      cultured hippocampal neurons after anoxia/reoxygenation.

PMID- 21180052
TI  - [Studies on properties of depotentiation of long-term potentiation induced by low
      frequency stimulation in CA1 neurons of rat hippocampal slices].
AB  - AIM AND METHODS: The parameters of low frequency stimulation (LFS) were altered
      systematically (frequencies of 1, 3 or 5 Hz; number of pulses of pulses of 300 or
      900; and time lag after high frequency stimulation (HFS) of 20 or 100 min) and
      examined their effects on depotentiation (DP) of long-term potentiation (LTP) of
      synaptic transmission in CA1 neurons in hippocampal slices of rat. RESULTS: LTP
      could be induced by HFS (two trains of 100 Hz, 100 pulses, separated by 30 s) and
      be reversed to produce DP by a train of LFS of 900 pulses at 3 Hz given 20 min
      after HFS. DP induced by LFS could be blocked by NMDA receptor antagonist AP5 (50
      micromol/L). And significantly reduced effect was observed for LFS at 1 Hz or 5
      Hz, with smaller numbers of pulses or a longer time lag from LFS to HFS.
      CONCLUSION: The above results indicate that DP induced in CA1 neurons of rat
      hippocampal slices is strongly dependent on the parameters of LFS, and the
      process may be mediated through the NMDA receptor.

PMID- 21180053
TI  - [Approach to the relationship between the changes of the content of free zinc in
      hippocampus and ischemic neuronal damage].
AB  - AIM: To make approach to the relationship between the changes of free zinc and
      ischemic neuronal damage in hippocampus after forebrain ischemia/reperfusion.
      METHODS: The models of forebrain ischemia/reperfusion were established in rats.
      The contents of free Zn2+ were measured by TSQ fluorescence method. The Zn2+
      chelator (CaEDTA) was injected into lateral ventricles in order to evaluate the
      effect of free Zn2+ on ischemic neuronal damage. RESULTS: (1) Zn2+ fluorescence
      in the hilus of dentate gyrus, CA3 region and the stratum radiatum and stratum
      oriens of CA1 decreased slightly at forty-eight hours after reperfusion. From
      seventy-two hours to ninety-six hour after reperfusion, the decreased
      fluorescence gradually returned to the normal level, but some fluorescence dots
      were found in pyramidal neurons of CA1 and the hilus of dentate gyrus. Seven days
      after reperfusion, all the changes of the fluorescence almost recovered. (2) The
      cell membrane-impermeable Zn2+ chelator CaEDTA could reduce the intracellular
      concentration of free Zn2+ and reduced neuronal damage after forebrain
      ischemia/reperfusion. CONCLUSION: (1) The synaptic vesicle Zn2+ released and then
      translocated into postsynaptic neurons after forebrain ischemia/reperfusion and
      played a role in ischemic neuronal damage. (2) The cell membrane-impermeable
      chelator CaEDTA could provide neuroprotection.

PMID- 21180054
TI  - [The NGF mRNA expression in the myocardium of rats during postnatal various
      period].

PMID- 21180055
TI  - [Effects of morphine on K+ currents in caudate nucleus of neonatal rat].
AB  - AIM: The effects of morphine on the potassium ionic currents of caudate nucleus
      neurons of neonatal rat were studied. METHODS: Using of whole cell voltage clamp
      technique on caudate nucleus neurons, applied morphine chronically or acutely on
      it. In order to research the effects of morphine for voltage-gated of potassium
      ionic currents. RESULTS: The amplitude of potassium ionic currents are increased
      by applied morphine acutely in caudate nucleus from (2.6 +/- 0.4) nA to (3.3 +/-
      0.5) Na, naloxone can block the effect of morphine on K+ current and the currents
      are decreased to (2.4 +/- 0.4) nA. If applied morphine in caudate nucleus
      chronically, the amplitude of potassium ionic currents are increased from (2.6 +/
      0.4) nA to (3.1 +/- 0. 5) nA. After applied naloxone, the currents are decreased
      to (2.4 +/- 0.4) nA. CONCLUSION: The effects of morphine increased potassium
      ionic currents by micro-opioid receptor mediated and induced the hyper
      polarization of neurons, leading to inhibition of neural activity.

PMID- 21180056
TI  - [The role of dorsomedial hypothalamic nucleus in the cardiovascular responses
      induced by habenular nucleus stimulation and inhibitory effect of deep peroneal
      nerve].
AB  - AIM: To explore whether dorsomedial hypothalamic nucleus (DMH) is involved in the
      cardiovascular responses induced by habenular nucleus (Hb) stimulation and
      inhibitory effect of deep peroneal nerve (DPN) stimulation on above responses or
      not and to analysis transmitter mechanism. METHODS: Experiments were performed on
      white male rabbits anesthetised with chloralose and urethan. Experimental data
      were collected by means of stimulating Hb and DPN, recording arterial blood
      pressure and ectal electrocardiogram (EECG) and microinjecting transmitter
      blocker. RESULTS: Prominent pressor and ischemic EECG segment changes were
      elicited by Hb stimulation (P < 0.01) Microinjecting kynurenic acid into
      ipsilateral DMH had partial blocking effect on pressor and ischemic EECG-ST
      segment changes induced by Hb stimulation (P < 0.01). Stimulation of bilateral
      DPN prominently inhibited the pressor and ischemic EECG-ST changes induced by Hb
      stimulation (P < 0.01, P < 0.05). Microinjecting naloxone into ipsilateral DMH
      decreased the inhibitory effect of DPN stimulation on above cardiovascular
      responses elicited by Hb stimulation (P < 0.01, P < 0.05). CONCLUSION: Glutamic
      acid receptor in DMH is involved in pressor and ischemic changes induced by Hb
      stimulation. DMH and opiate peptide receptors in DMH are involved in the
      inhibitory effect of DPN stimulation on pressor and ischemic changes induced by
      Hb stimulation.

PMID- 21180057
TI  - [Changes of contents of plasma ET and CGRP after resuscitation in rabbit sudden
      cardiac arrest].

PMID- 21180058
TI  - [Blind patch clamp studying on the properties of calcium channel of pyramidal
      neurons in the rat hippocampal slices].
AB  - AIM AND METHODS: By using blind whole-cell recording techniques, the dynamic
      properties of voltage-gated Ca2+ channel of CA1 pyramidal neuron in rat
      hippocampal slices were investigated. RESULTS: The voltage-gated Ca2+ channel of
      CA1 pyramidal neuron in rat hippocampal slices has following features: (1) The
      threshold potential of activation is relatively lower. The mean value is -49.3 +/
      8.6 mV with range from -65 to -30 mV (n = 23). (2) Current decay is Ca(2+) 
      dependent and its time constant (tau) is longer with a wide range from 100 to 700
      ms (n = 12). (3) The steady-state inactivation is voltage-dependent and the half
      inactivation potential (V1/2) is -55.4 +/- 9.7 mV, slope factor (k) is 5.3 +/-
      0.9 (n = 10). (4) The reversal potential (E(rev)) of Ca2+ channel is 55 +/- 13 mV
      (n = 10) when extracellular Ca2+ concentration is 2.5 mmol/L. (5) Tail current,
      which is voltage-independent, primarily has only one component. In addition, Ca2+
      channel is insensitive to verapamil and nifedipine. CONCLUSION: N-type Ca2+
      channel is strongly suggested in CA1 pyramidal neuron in rat hippocampal slices.

PMID- 21180059
TI  - [The central exciting role of galanin antagonist M40 at low concentration].

PMID- 21180060
TI  - [Effects of tetanization of the right caudate-putamen on the depth electrographs
      in the hippocampus or medial temporal lobe neocortex electrographs in rats].
AB  - AIM: To study the role of the caudate-putamen (CPu)-hippocampus (HPC)-medial
      temporal lobe neocortex (MTNC) neural pathway in re-establishment of
      pathophysiological neural networks related to epileptogenesis. METHODS:
      Experiments were performed under anaesthesia on 45 SD rats. The right HPC, the
      right MTNC, bilateral HPC, the right HPC and the right MTNC depth electrographs
      were recorded with bipolar concentric electrodes. Tetanization (60 Hz, 2 s, 0.4 -
      0.6 mA) of the right CPu or of the right HPC trains were used to establish acute
      rat epilepsy model. These depth electrographs were detected before or after
      tetani were delivered about 10 times at 10 min intervals. RESULTS: Tetanization
      of the right CPu induced (1) primary afterdischarges and unilateral or bilateral
      HPC electrographic afterdischarges and kindling effect or inhibition-rebound
      kindling effect were induced by repetitive tetani into the right CPu. (2) After
      injection of scopolamine (0.05 mg/kg i.p.), 3 Hz slow oscillations in HPC
      electrographs exhibited long-term potentiation followed by repetitive tetani into
      the right CPu. (3) After administration of scopolamine (i.p.) electrographic
      oscillations at 3Hz with synaptic modification in bilateral HPC were induced and
      epileptiform activities in the RHPC were synchronized with those in the RMTNC.
      CONCLUSION: Pathophysiological neural networks from the Cpu into the HPC might be
      reestablished by overactivation of the right CPu, in which two hemispheres are
      involved while temporal lobe epileptogenesis was facilitated.

PMID- 21180061
TI  - [Changes of ultrastructure in cardiovascular endothelium and its ICAM-1
      expression in rat after repetitive positive acceleration exposures].
AB  - AIM: To observe the change of cardiovascular endothelium's ultrastructure and its
      intercellular adhesion molecules-1 (ICAM-1) expression in rat after repetitive
      high positive acceleration (+ Gz) exposures and further to explore the mechanisms
      of myocardial injuries induced by high + Gz stress. METHODS: Thirty male Wistar
      rats were randomly divided into three groups: control group, + 1Gz group and +
      10Gz group (n = 10 for each). The rats of + 10Gz group were exposed to five
      plateaus at + 10Gz for 30s with + 1Gz 1 min intervals, 3 times a week, for 3
      weeks, while rats of + 1Gz group subjected to + 1Gz for 5 mim daily. The control
      group didn't undergo acceleration stress. The rats were decapitated in the next
      day after the last centrifuge run and myocardium were immediately dissected from
      left ventricles for ultrastructural examination using transmission electron
      microscope and immunohistochemical staining of ICAM-1. RESULTS: The
      ultrastructural changes of the cardiovascular endothelium were observed in rats
      of 10Gz group, including endothelium edema and platelet aggregating in lumen of
      blood vessel. Also, the expression of ICAM-1 in + 10Gz stressed rats increased
      significantly (P < 0.05). While there was no difference between control group and
      + 1Gz group in ultrastructure of cardiovascular endothelium and its ICAM-1
      expression. CONCLUSION: The results suggested that repeated high + Gz exposures
      could injury cardiovascular endothelium of rat and increase ICAM-1 expression,
      which indicated cell adhesion molecules (CAMs) inducing inflammation took part in
      myocardial injuries induced by high + Gz stress.

PMID- 21180062
TI  - [Effect of changes in pH on intracellular Ca2+ and cell length of myocytes].
AB  - AIM: To examine the effects of pHi on [Ca2+]i, cell length and Ca2+ sensitivity
      of myofilaments in rat myocyte. METHODS: We used microscopic spectral imaging
      approach to monitor simultaneously [Ca2+]i, pHi and cell length with fluorescent
      indicator indo-1 and SNARF-1 in isolated single rat myocyte. RESULTS: Exposure of
      cell to 20 mmol/L Sodium Propionate induced an intracellular acidosis which
      increased slightly systolic and diastolic [Ca2+]i, decreased the cell shortening
      (CS) and Ca2+ sensitivity of myofilament (P < 0.01). Exposure of cell to 15
      mmol/L NH4Cl induced an intracellular alkalosis which decreased systolic and
      diastolic [Ca2+]i, increased the cell shortening and Ca2+ sensitivity of
      myofilament (P < 0.01). CONCLUSIONS: In the early time of acidosis, [Ca2+]i, as
      well as cell length increases respectively. While alkalosis, [Ca2+]i and cell
      length decreases respectively. The effect of acidosis and alkalosis on Ca2+
      sensitivity presents non-linear relationship, i.e. the effect of acidosis on
      sensitivity, caused by pHi change, is less than that of alkalosis.

PMID- 21180063
TI  - [Comparison of pharmacological characteristics of the endothelial target for
      acetylcholine between big artery and small artery].
AB  - AIM: To compare the differences of pharmacological characteristics of the
      endothelial target for acetylcholine (ETA) between rat aorta and tail artery.
      METHODS: Differences in the endothelium-dependent relaxation induced by
      acetylcholine (ACh: 10(-8) - 10(-4) mol/L) were studied using isolated rat tail
      artery helical strips and aortic rings, so that the pharmacological
      characteristics of ETA in small artery can be observed. RESULTS: ACh-induced
      endothelium-dependent relaxation was observed both in rat tail artery strips and
      in aortic rings precontracted with potassium chloride (60 mmol/L) in a
      concentration-dependent manner. In tail artery this effect was partially blocked
      by L-N(omega)-Nitro-arginine methyl ester (L-NAME: 10(-4) mol/L) or methylene
      blue (MB: 10(-5) mol/L), together with indomethacin (Indo: 10(-4) mol/L), but in
      aorta it was completely blocked by L-NAME or MB. CONCLUSION: It is different of
      the pharmacological characteristics of ETA between big artery and small artery. A
      non-NO and non-PGI2 relaxing factor, together with nitric oxide (NO) and
      prostacyclin (PGI2), mediates endothelium-dependent vasorelaxation induced by ACh
      in small artery, but NO may be the principal endothelial vasodilator substance in
      big artery.

PMID- 21180064
TI  - [The effect of carbon monoxide on the proliferation of PASMCs under hypoxia and
      the mechanism].
AB  - AIM AND METHODS: MTT colorimetric assay, in situ hybridization and
      immunocytochemistry were performed to investigate the effect of endogenous and
      exogenous CO on the proliferation of PASMCs and the expression of PDGF-B and
      protooncogene bcl-2, P53 (mutant type) in PASMCs, in order to elucidate the
      mechanism by which CO suppressed the proliferation of PASMC in hypoxic
      environment. RESULTS: The results of in situ hybridization of PDGF-B mRNA and
      immunocytochemical staining of PDGF-B were negative. Hypoxia could upregulate the
      expression of Bcl-2, mutant P53 protein in comparison with the control group (P <
      0.01). Compared with the hypoxic group, the expression of Bcl-2 and mutant P53
      were decreased after treated with hemin or CO, but increased after treated with
      hemoglobin (P < 0.01). CONCLUSION: CO could suppress the expression of oncogene
      bcl-2 and mutant P53. This partially explained how CO suppressed the
      proliferation of PASMCs in hypoxic environment.

PMID- 21180065
TI  - [The roles of carbon monoxide on hypoxic pulmonary vasoconstriction].
AB  - AIM AND METHODS: To study the roles of carbon monoxide on hypoxic pulmonary
      vasoconstriction (HPV) by investigating the effects of exogenous carbon monoxide
      and heme oxygenase inhibitor ZnPPIX on hypoxic vasoconstriction reaction of
      isolated rat pulmonary arterial rings (PAR). RESULTS: Hypoxia caused constriction
      in PAR preconstricted by PE. Both ZnPPIX and carbon monoxide inhibited hypoxic
      pulmonary constriction significantly by increasing the cGMP level after hypoxia.
      CONCLUSION: ZnPPIX and exogenous carbon monoxide can inhibit HPV. The reduction
      of cGMP induced by the decreased of CO may be one of reasons of HPV.

PMID- 21180066
TI  - [Studying the mechanism of heart rate slowing down after birth by the method of
      HRV power spectrum analysis].
AB  - AIM: To explore the neurological mechanism of heart rate slowing down after birth
      and to investigate if the heart itself participates in the process. METHODS: With
      the method of HRV power spectrum analysis, the regulatory mechanisms of autonomic
      nerves over heart rate were studied on different age groups of human beings and
      rabbits. Similar experiments were carried out on isolated perfused rabbit hearts
      in order to study if the heart itself were involved in the process of heart rate
      slowing down as they grew up. RESULTS: The ratio of parasympathetic tone to
      sympathetic one is significantly increased as a child or rabbit grows up while
      the heart rate becomes slower. The spontaneous beating of isolated rabbit heart
      also slows down as the rabbit becomes older. CONCLUSION: Both of the nerve factor
      and heart itself are involved in the process of slowing down of heart rate as a
      child grows up.

PMID- 21180067
TI  - [Alterations of erythrocyte deformability and membrane protein after high
      intensity training and recovery in rats].
AB  - AIM AND METHODS: The purpose of this investigation was to determine the changes
      of erythrocyte deformability, band-3 protein and actin in the definite volume of
      erythrocyte membrane after high intensity running training and recovery in rats.
      RESULTS: Long-term training could significantly improve erythrocyte deformability
      and the quantity of membrane proteins. Erythrocyte deformability, band-3 protein
      and actin decreased transitorily at varying degrees after inadaptable high
      intensity exercise. One and two week training could improve erythrocyte
      deformability, the quantity of band-3 protein and actin after recovery.
      CONCLUSION: Alterations of erythrocyte membrane protein after high intensity
      training could cause the change in erythrocyte membrane structure and hence
      influenced erythrocyte deformability. That was maybe one of mechanisms of
      training effecting erythrocyte deformability.

PMID- 21180068
TI  - [The influence on the expression of mRNAs encoding subunits of the NMDA receptor
      during postnatal development of rat by continued one-side block of hearing air
      conduction].

PMID- 21180069
TI  - [Effect of PDGF-AA on [Ca2+]i in vascular smooth muscle cells in SHRs].
AB  - AIM: To explore the relationship between proliferation and hypertrophy of
      vascular smooth muscle cells and PDGF-AA and PDGFR-alpha expression in SHRs and
      the role of [Ca2+]i in it. METHODS: Express difference of PDGF-AA, PDGFR-alpha,
      PDGFR-beta in SHR/WKY-VSMC was observed by Western blot. The effect of Ca2+
      inhibitor (nimodipine) on proliferation, hypertrophy and free Ca2+ concentration
      of SHR-VSMC induced by PDGF-AA was observed by Western blot, [3H] incorporation
      and fluorescent digital image technique. RESULTS: PDGF-AA and PDGFR-alpha
      expression was markedly increased in SHR-VSMC than in WKY-VSMC, but PDGFR-beta
      was not different in SHR and WKY-VSMC. PDGF-AA-stimulated PCNA expression, [3H]
      incorporation and [Ca2+]i increasing were observed in SHR-VSMC. Dose-dependent
      nimodipine-inhibited PCNA expression, [3H] incorporation and [Ca2+]i increasing
      induced by PDGF-AA also were observed in SHR-VSMC. CONCLUSIONS: Spontaneously
      expression increasing of PDGF-AA and PDGFR-alpha in spontaneously hypertension
      rats (SHRs) may be one of the important factors on vascular reactivity and
      vascular modeling mediated through proliferation and hypertrophy in SHR-VSMC, and
      [Ca2+]i play an important role in this process.

PMID- 21180070
TI  - [Study on construction of a plasmid vector carrying human hepatocyte growth
      factor gene and activity of its expression product].
AB  - AIM: To construct a plasmid carrying hepatocyte growth factor gene and
      investigate its effects in vitro. METHODS: A complementary DNA (cDNA) clone for
      human HGF was isolated from human placental cDNA, then subcloned into pUDK
      vector, which was constructed by ourselves, to form the pUDKH plasmid. The
      transfection efficiency and the expression level of HGF and VEGF were evaluated
      by transfecting pUDK or pUDKH into primary rat skeletal muscle cells. The
      biological effects of HGF-expressing product at different doses on endothelial
      cells were investigated in vitro, and assessed by MTT. RESULTS: The primary rat
      skeletal muscle cells could be transfected efficiently with pUDKH (0.057%), and
      secreted HGF(16 -18 ng/4 x 10(5) cells) and VEGF proteins. The expressing product
      could significantly stimulate proliferation of human umbilical vein endothelial
      cells, in a dose-dependent manner (P < 0.05). CONCLUSION: pUDKH has the potential
      application in vivo to treat ischemic diseases.

PMID- 21180071
TI  - [Influence of rhIL and rhTPO on the number and quality of platelet and
      coagulability of whole blood in monkeys].

PMID- 21180072
TI  - [Effects of free fatty acids on insulin signaling proteins in rat islet cells].
AB  - AIM: To investigate whether free fatty acid impair insulin signaling proteins to
      inhibit insulin action in rat islet cells. METHODS: After rat islet cells were
      incubated with palmitate (0.25 mmol/L) or oleate (0.125 mmol/L) for 12 hours, 24
      hours and 36 hours, western bolt was used to assess the protein abundance of
      cPKCalpha, Grb2 and FERK2. RESULTS: The protein content of cPKCalpha were
      significantly upregulated and the protein abundance of Grb2 and ERK2 was
      decreased comparing with control in rat islet cells after incubated with free
      fatty acids. CONCLUSIONS: Free fatty acids may inhibit insulin activity in rat
      islet cells through up-regulating the expression of cPKCalpha or down-regulating
      the expression of Grb2 and ERK2.

PMID- 21180073
TI  - [Expression of interleukin-2 receptors on breast cancer cell line MCF-7 cells].
AB  - AIM: To investigate the expression of interleukin-2 receptors (IL-2Rs) on MCF-7
      cells, estradiol's regulation of IL-2Rs expression and the influence of IL-2 on
      the proliferation of MCF-7 cells. METHODS: Immunocytochemistry and flow
      cytometric analysis were used to investigate the expression of interleukin-2
      receptors (IL-2Rs) by using of specific IL-2R polyclonal antibody; MTT method and
      3H-TdR incorporation method were used to examine the changes of proliferation of
      MCF-7 cells. RESULTS: IL-2Ralpha, beta, gamma like immunoreactive substances can
      be found on MCF-7 cells and the IL-2Rgamma immunostaining was more strong than
      the other two. Estradiol of 10(-6) mol/L can increase the percentage of
      immunoreactive cells of IL-2Ralpha, beta and the expression of IL-2Rgamma.
      Exogenous addition of recombinant IL-2 of 100 U/ml to 1 000 U/ml can
      significantly increase the proliferation of MCF-7 cells. CONCLUSION: MCF-7 cell
      can express IL-2R and estradiol can regulate their expression, IL-2 can influence
      the proliferation of MCF-7 cells.

PMID- 21180074
TI  - [Effects of irradiation and W11 - a12 on Ca(2+) -activated K+ channel in 3T3
      cells].

PMID- 21180075
TI  - [Effects of Momordica saponins on endocrine function in senile mice].
AB  - AIM: To study the regulation effects of Momordica saponins on endocrine function
      in senile mice. METHODS: 15-month Kunming mice (female), were divided into senile
      control group (SC), experimental group 1 and 2 (E1 and E2). 10 4-month mice were
      as young control group (YC). All mice were fed with general foodstuff, SC and YC
      drank tap water, while two experimental groups drank tap water supplied to 100
      mg/L and 200 mg/L Momordica saponins respectively. Serum was assayed after 5
      weeks. At the same time, levels of estrogen receptor and its mRNA were assayed in
      cultured thymocyte from 12-month rat. RESULTS: Serum ACTH and estradiol levels
      declined markedly in senile mice compared with young mice. ACTH levels increased
      in some extent in two experimental groups, while there had significant difference
      only in E2. Serum estradiol increased obviously, but there was no significant
      distinct between E1 and E2. The most important was that ER levels increased
      obviously, and there was no any change of ER mRNA levels in rat thymocyte
      cultured in medium contained different content of Momordica saponins. CONCLUSION:
      Momordica saponins could improve endocrine function in senile mice by increasing
      ACTH level and expression of ER.

PMID- 21180076
TI  - [Modulation with bupleurum root on brain electrical activities in epileptic
      model].
AB  - AIM: To study the effect of bupleurum root on epileptic seizure. METHODS: The
      rabbits and rats were injected by pilocarpine as epileptic models, and observed
      the effect of bupleurum on the electroencephalogram (EEG) and hippocampal slice
      by electroencephalograph and glass microelectrode extracellularly. RESULTS: The
      seizure time and duration of each major seizure of epilepsy were significantly
      shortened and the interval of seizure significantly prolonged (P < 0.05) after
      intraabdominal injection of bupleurum root. After instilling the injection of
      bupleurum root onto the slices could reduce the amplitude of evoked field
      potential in epileptic hippocampal slices remarkably, the average of fall is
      20.41%, and restore in 6.86 minutes on average (P < 0.001). CONCLUSION: Bupleurum
      root can inhibit the brain electrical activities in epileptic model, it is
      suggest that bupleurum has the distinct effect of antiepilepsy.

PMID- 21180077
TI  - [Effect of cysteamine on the pancreatic secretion and enzymatic activity in
      geese].
AB  - AIM: To know the effect of cysteamine on the pancreatic secretion and enzyme
      activity in geese. METHODS: Eight adult geese fitted chronic pancreatic and
      duodenal cannulas were used to evaluate the effect of cysteamine (CS) on the
      pancreatic secretion and enzyme activity. The experiment was consist of control
      and treated phase. CS was added in the diet at the dosage of 100 mg/kg bw on the
      first day of treated phase. The birds were free fed at daytime (8:00-20:00) and
      fasted at nighttime (20:00-8:00). The pancreatic juice samples were collected
      continuously for three days in each phase. RESULTS: CS increased the average rate
      of pancreatic secretion by 240.16% (P < 0.01), in which that of daytime was
      elevated by 234.45% (P < 0.01), while that of nighttime elevated by 253.70% (P <
      0.01). The secretion volume at daytime was more than that of night. CS increased
      trypsin activity by 49.05% (P < 0.01), whereas lipase and amylase activity was
      reduced by 25.44% (P < 0.01) and 21.95% (P < 0.01) separately. The one hour total
      activity of trypsin, lipase and amylase were elevated by 406.88% (P < 0.01),
      153.58% (P < 0.01) and 166.59% (P < 0.01) respectively. Ratios of pancreatic
      secretion were different between day and night. CONCLUSION: These results
      indicate that CS can affect the pancreatic juice secretion and pancreatic enzyme
      activity by depleting the somatostatin, so that benefits to improve the digestive
      foundation and supply more nutrition for quickly growing in geese.

PMID- 21180078
TI  - [Activation of the Mauthner cell by direct stimulation on vagus nerve in crucian
      carp].
AB  - AIM: To investigate the influence of the vagus nerve on the electrophysiological
      properties in the Mauthner cell soma and the relationship between soma and
      viscus. METHODS: The microelectrode recording technique was used to explore the
      electrophysiological properties in the Mauthner cell when stimulating the right
      vagus. RESULTS: At lower stimulation strength a graded and compound excitatory
      postsynaptic potentials (EPSP), formed by two components with lower amplitude,
      were recorded on the Mauthner cell in a crucian carp. As the intensity of
      stimulus increased, the amplitude became larger and lasting time longer. With the
      stimulations high enough, action potentials (AP) were evoked on the EPSP.
      CONCLUSION: (1) Action potential can be induced on M cell by a direct stimulation
      on vagus nerve, which is in controversy with previous reports. (2) The neural
      pathway projecting from vagus to M cell is composed of a set of neuronal chains
      with excitatory and/or inhibitory members, the activation of M cell depends on
      the relationship between excitatory and inhibitory neuron.

PMID- 21180079
TI  - [Simultaneously optical recording of membrane potential in population vestibular
      ganglion neurons].
AB  - AIM: To investigate membrane electro-physiological features in vestibular
      ganglion neuronal population using a voltage-sensitive dye and optical recording
      technique. METHODS: Dissociated and cultured mouse vestibular ganglion neurons
      were stained with an absorption voltage-sensitive dye, RH 155, and were imaged in
      16 x 16 elements Photodiode arrays (PDA) optical recording system. RESULTS: When
      the cells were depolarized during perfusion with 150 mmol/L potassium solution,
      optical absorption of the dye that bound to the external surface of neuron
      membranes increased. The relative ratio (delta I/I) of optical absorption change
      was 0.23% +/- 0.08% (x +/- s, n = 28). These optical responses were wavelength
      dependent. Under our experimental conditions, photo toxicity and pharmacological
      effects of the dye were either absent or insignificant. CONCLUSION: Our results
      suggest that optical recording provides a new, practical and less toxic method to
      simultaneously monitor changes in membrane potential from several cultured
      vestibular ganglion cells.

PMID- 21180081
TI  - [Improvement on experimental equipment of mouse asthma model on determination of
      ventilative function].

PMID- 21180082
TI  - [Effect of Qingkailing Injection on children with respiratory syncytial virus
      pneumonia of phlegm-heat obstructing Fei syndrome pattern at different time
      points].
AB  - OBJECTIVE: To evaluate the curative effect of Qingkailing Injection (QKL) for
      treatment of children's respiratory syncytial virus pneumonia of phlegm-heat
      obstructing Fei syndrome pattern (SVP-PH) depending upon main symptom assessment.
      METHODS: A Chinese-Western medicine comparative trial was conducted on 206
      children with SVP-PH in two groups treated with Ribavirin injection plus compound
      guaiacol potassium sul-fonale oral solution (as control group) and QKL injection
      plus Ertong Qingfei oral liquid (as treated group) respectively, for 10 days. The
      curative effectiveness on four main symptoms (fever, cough, sputum and short
      breath) were evaluated at different time-points. RESULTS: The effectiveness in
      the treated group at various time-points was superior to that in the control
      group, showing the earlier initiating time (on the 4th day) and the
      preponderances on cough and sputum ran all through the whole course. CONCLUSION:
      Chinese medicine shows a multi-target effect in treating children's SVP-HP.

PMID- 21180083
TI  - [Scanning electron microscopy investigation of canal cleaning after canal
      preparation with nickel titanium files].
AB  - INTRODUCTION: Root canal preparation is the most important phase of endodontic
      procedure and it consists of adequate canal space cleaning and shaping. In recent
      years, rotary instruments and techniques have gained importance because of the
      great efficacy, speed and safety of the preparation procedure. OBJECTIVE: The aim
      of this research was to investigate the influence of different NiTi files on the
      canal wall cleaning quality, residual dentine debris and smear layer. METHODS:
      The research was conducted on extracted human teeth in vitro conditions. Teeth
      were divided in 7 main groups depending on the kind of instruments used for root
      canal preparation: ProTaper, GT, ProFile, K-3, FlexMaster, hand ProTaper and hand
      GT. Root canal preparation was accomplished by crown-down technique. Prepared
      samples were assessed on scanning electron microscopy JEOL, JSM-6460 LV. The
      evaluation of dentine debris was done with 500x magnification, and the evaluation
      of smear layer with 1,000 times magnification. Quantitive assessment of dentine
      debris and smear layer was done according to the criteria of Hulsmann. RESULTS:
      The least amount of debris and smear layer has been found in canals shaped with
      ProFile instruments, and the largest amount in canals shaped with FlexMaster
      instruments. Canal cleaning efficacy of hand GTand ProTaperfiles has been similar
      to cleaning efficacy of rotary NiTi files. Statistic analysis has shown a
      significant difference in amount of dentine debris and smear layer on the canal
      walls between sample groups. shaped with different instruments. CONCLUSION:
      Completely clean canals have not been found in any tested group of instruments.
      The largest amount of debris and smear layer has been found in the apical third
      of all canals. The design and the type of endodontic instruments influence the
      efficacy of the canal cleaning.

PMID- 21180084
TI  - [Chlorhexidine as a root canal irrigant--antimicrobial and scanning electron
      microscopic evaluation].
AB  - INTRODUCTION: Selection of irrigant is very important for long-term success of
      root canal therapy. OBJECTIVE: This study was undertaken to evaluate the
      antimicrobial effects of 2% chlorhexidine digluconate solution (CHX) against five
      selected microorganisms and to evaluate its efficacy in root canal cleaning.
      METHODS: In this study, by agar diffusion test, were evaluated antimicrobial
      effects of three root canal irrigants: 5.25% NaOCl, 2.5% NaOCl and 2% CHX. The
      microorganisms tested in this study were Staphylococcus aureus, Streptococcus
      mutans, Enterococcus faecalis, Escherichia coli and Candida albicans. A scanning
      electron microscope was used to evaluate root canal cleaning ability of 5.25%
      NaOCl, 2.5% NaOCl, 2% CHX and 15% EDTA. Twelve extracted single-root human teeth
      were divided into four groups depending on the irrigant used during
      instrumentation. Mechanical preparation was performed with Step back technique
      and K files. Data were analysed statistically by Student's t-test. RESULTS: 5.25%
      NaOCl was the most effective against all tested microorganisms. 2.5% NaOCl and 2%
      CHX showed antimicrobial effects against all tested microorganisms but zones of
      inhibition were smaller.The best results in root canal walls cleaning were
      obtained in the group where the irrigant was 15% EDTA (score 2.33). In 5.25%
      NaOCl, 2.5% NaOCl and 2% CHX groups, there was more smear layer (score 4 and 5).
      CONCLUSION: 2% chlorhexidine digluconate showed strong antimicrobial effect on
      the tested microorganisms, but was not effective in cleaning root canal walls.

PMID- 21180085
TI  - [Oral lesions in patients with psychiatric disorders].
AB  - INTRODUCTION: Oral diseases in psychiatric patients are usually a result of bad
      oral hygiene and psychopharmaceutical side-effects. OBJECTIVE: The aim of this
      study was to detect oral lesions in patients hospitalized in psychiatric
      institutions with the confirmed diagnosis of psychiatric illness and mood
      disorder with psychotic characteristics, as well as to discover the factors that
      can influence these oral lesions. METHODS: Cross-section study consisted of 186
      hospitalized patients with psychiatric disorders in the experimental group, out
      of whom 87 were males and 99 females. Patients were aged from 18 to 59 years,
      mean age 46.0 +/- 8.0 years. The control group consisted of 186 healthy persons
      matched for age and gender. Data on oral lesions were obtained within history and
      clinical examination of the oral cavity. Other medical data were collected from
      medical documentation. Statistical analysis was performed by Student's t-test,
      chi-square test and logistic regression. RESULTS: Dry mouth was registered in
      78.5% of patients. The difference in tongue and lip lesions, burning and stinging
      symptoms, bruxism, facial pain, low saliva rates, halitosis, taste changes and
      swallowing difficulties between the patients and healthy persons was highly
      statistically significant (p < 0.001). Age and gender, as well as the factors of
      main disease, influence burning and stinging, bruxism, low saliva rates,
      swallowing difficulties, taste changes and facial pain of the psychiatric
      patients. CONCLUSION: Results imply that psychiatric patients are more frequently
      involved with oral lesions than healthy persons. It is necessary to organize
      specific preventive and educational oral health programmes with these patients,
      as well as with doctors who treat the basic illness.

PMID- 21180086
TI  - [Trends of risk factors in coronary surgery].
AB  - INTRODUCTION: In current era of widespread use of percutaneous coronary
      interventions (PCI), it is debatable whether coronary artery by-pass graft (CABG)
      patients are at higher risk. OBJECTIVE: The aim of the study was to evaluate
      trends in risk profile of isolated CABG patients. METHODS: By analysing the
      EuroSCORE and its risk factors, we reviewed a consecutive group of 4675 isolated
      CABG patients, operated on during the last 8 years (2001-2008) at our Clinic. The
      number of PCI patients was compared to the number of CABG patients. For
      statistical analyses, Pearson's chi-square and ANOVA tests were used. RESULTS:
      The number of PCI increased from 159 to 1595 (p < 0.001), and the number of CABG
      from 557 to 656 (p < 0.001). The mean EuroSCORE increased from 2.74 to 2.92 (p =
      0.06). The frequency of the following risk factors did not change over years:
      female gender, previous cardiac surgery, serum creatinine > 200 micromol/l, left
      ventricular dysfunction and postinfarct ventricular septal rupture. Chronic
      pulmonary disease, neurological dysfunction, and unstable pectoral angina
      declined significantly (p < 0.001). Critical preoperative care declined from 3.1%
      in 2001 to 0.5% in 2005, than increased and during the last 3 years did not
      change (2.3%). The mean age increased from 56.8 to 60.7 (p < 0.001) and
      extracardiac arteriopathy increased from 9.2% to 22.9% (p < 0.001). Recent
      preoperative myocardial infarction increased from 11% to 15.1% (p = 0.021), while
      emergency operations increased from 0.9% to 4.0% (p = 0.001). CONCLUSION: The
      number of CABG increases despite the enlargement of PCI. The risk for isolated
      CABG given by EuroSCORE increases over years. The risk factors, significantly
      contributing to higher EuroSCORE are: older age, extracardiac arteriopathy,
      recent myocardial infarction and emergency operation.

PMID- 21180087
TI  - [Influence of metabolism modifiers of cyclic nucleotides on contractility of
      right ventricle of rat heart with intact and removed endocardial endothelium].
AB  - INTRODUCTION: Endocardial endothelium, a natural biological barrier between
      circulating blood in heart ventricle and cells, creates a complex yet finely
      tuned balance of interactions with the immediate environment. OBJECTIVE: We
      investigated the roles of theophylline, nonspecific phosphodiesterase inhibitor,
      and imidazole, an activator of phosphodiesterase on contractility of the right
      ventricle of rat heart, with intact and removed endocardial endothelium. METHODS:
      Adult rats, of both sexes, type Wistar albino, were used in this experiment. All
      experiments were conducted on the preparations of the right ventricle using two
      experimental models. In the first experimental model, an endocardial endothelium
      (EE) was preserved, and in the second model, an endocardial endothelium (-EE) was
      removed using 1% solution Triton X-100. RESULTS: Theophylline (1 x 10(-2) mol/l)
      expressed the positive inotropic effect on the heart, regardless of the presence
      of the endocardial endothelium. Inotropic response as multiple process can be
      induced by inhibition of phosphodiesterase, accumulation of cyclic nucleotides
      and activation of Ca2+ channels. Imidazole (2 x 10(-3) mol/l) increased the
      contractility of the right ventricle of the heart with EE. The modulator effect
      of endocardial endothelium on contractility of imidazole proved to be
      significant. As imidazole influenced the contractility of the right ventricle
      only in the presence of the endocardial endothelium, it is assumed that its
      effect is mediated via deliverance of endothelial mediators with positive
      inotropic effect. CONCLUSION: An intact endocardial endothelium is necessary for
      completion of contractile performance of the heart.

PMID- 21180088
TI  - [Sudden cardiac death and acute drunken state--autopsy study].
AB  - INTRODUCTION: Sudden natural death occurs unexpectedly in apparently healthy
      subjects, or in persons during an apparent benign phase in the course of disease.
      The most common cause is sudden cardiac death, which is sometimes the first and
      last manifestation of coronary heart disease. Alcohol directly influences
      excitation of myocytes, and therefore provokes arrhythmias and possibly, sudden
      cardiac death. OBJECTIVE: To establish the frequency of sudden cardiac death in
      cases of acute alcohol intoxication, to determine blood alcohol concentration at
      the moment of death, and to determine frequency and level of ethanol intoxication
      in chronic alcohol abusers, as well as causes of sudden death in those cases.
      METHOD: Retrospective autopsy study was performed for a three-year-period. We
      analyzed cases of sudden natural death, in relation to age and gender, cause of
      death, and blood alcohol concentration (at least 0.5 g/L). We considered the
      person to be a chronic alcoholic abuser if gross examination of organs during
      autopsy showed changes typical for excessive and habitual alcohol consumption.
      RESULTS: Our sample consisted of 997 cases: 720 men and 277 women, average age
      62.0 +/- 15.2 years (min = 11; max = 98). Total of 753 of them died of sudden
      cardiac death: much more men (chi2 = 167.364; p = 0.000), significantly younger
      than women (t = 6.203; p = 0.000). We determined acute alcohol intoxication in 73
      persons--average blood alcohol concentration 1.85 +/- 1.01 g/L (min = 0.55; max =
      3.85), and 61 of them died of cardiovascular diseases (chi2 = 236.781; df = 5; p
      = 0.000). CONCLUSION: In our observed sample, not many persons were under acute
      alcohol intoxication (around 7%). Most commonly, they were chronic alcohol
      abusers who died due to exacerbation of chronic heart disease, mildly or
      moderately intoxicated--the younger, the drunker.

PMID- 21180089
TI  - [Importance of early detection of lung cancers with initial paraneoplastic
      manifestations].
AB  - INTRODUCTION: Lung cancers are mostly detected in the developed clinical stages,
      with clearly manifested pulmonary, extrapulmonary or metastatic manifestations.
      In the early disease stages, radiographic and clinical manifestations may be
      absent or mimicked. OBJECTIVE: The aim of this study was the timely detection of
      early pulmonary, extrapulmonary and paraneoplastic manifestations of lung cancers
      in order to apply the most appropriate treatment protocols. METHODS: We examined
      230 patients with lung cancer, among them 125 of the working study group with
      minimal pulmonary and/or initial paraneoplastic symptoms, and 105 patients in the
      control group with clear tumour manifestations. RESULTS: The symptom analysis
      revealed a statistically significantly lesser presence of the respiratory
      symptoms in the working study group (68%) in comparison with the control group of
      patients (97%) (chi2 = 29.996; p < 0.001). The analysis of radiographic
      presentations of lung cancer showed that there were significantly more patients
      with normal findings in the working group (6.4%) than in the control group--1.9%
      (p > 0.05), and a positive bronchoscopic finding of the centrally localized
      tumour (mainly right upper lobe) was confirmed in patients of both groups with
      normal radiographic findings. The number of diagnosed patients in earlier
      clinical disease stages (I, II, IIIa) with better prognosis in non-small cell
      lung cancer was significantly higher (chi2 = 19.149; p < 0.001) in the working
      group (71.1%) in comparison with the control group (38.1%). Small cell lung
      cancer was more frequently diagnosed in the stage of limited disease in the
      working (80%) than in the control group (38.1%) (chi2 = 10.039; p < 0.05). With
      regard to treatment administration, there is a statistically significant
      difference (chi2 = 4.013; p = 0.0452) in the frequency between the use of
      chemotherapy and highly significant difference (chi2 = 22.044; p < 0.001) in the
      frequency of use of surgical treatment in the working group in comparison with
      the control group--both chemotherapy and surgery treatment were more frequent in
      the patients of the working group. CONCLUSION: Recognizing the initial pulmonary,
      extrapulmonary or paraneoplastic manifestations as well as performing diagnostic
      procedures in due time represent the most important guidelines in early detection
      and the most efficacious therapeutic choice in lung cancer.

PMID- 21180090
TI  - [Transitory hypothermia as early prognostic factor in term newborns with
      intrauterine growth retardation].
AB  - INTRODUCTION: According to numerous researches, transitory hypothermia is a part
      of the neonatological energetic triangle and represents a significant prognostic
      factor within morbidity and mortality in newborns with intrauterine growth
      retardation (IUGR), that are, due to their characteristics, more inclined to
      transitory hypothermia. OBJECTIVE: The aim of the study was an analysis of
      frequency of transitory hypothermia in term newborns with IUGR, as well as an
      analysis of frequency of the most frequent pathological conditions typical of
      IUGR newborns depending on the presence of transitory hypothermia after birth
      (hypoglycaemia, perinatal asphyxia, hyperbilirubinaemia and hypocalcaemia).
      METHODS: The study included 143 term newborns with IUGR treated at the
      Neonatology Ward of the Gynaecology-Obstetrics Clinic "Narodni front", Belgrade.
      The newborns were divided into two groups: the one with registered transitory
      hypothermia--the observed group, and the one without transitory hypothermia--the
      control group. The data analysis included the analysis of the frequency of
      transitory hypothermia depending on gestation and body mass, as well as the
      analysis of pathological conditions (perinatal asphyxia, hypoglycaemia,
      hypocalcaemia, hyperbilirubinaemia) depending on the presence of hypothermia. The
      analysis was done by statistical tests of analytic and descriptive statistics.
      RESULTS: In morbidity structure dominate hypothermia (65.03%), hypoglycaemia
      (43.36%), perinatal asphyxia (37.76%), hyperbilirubinaemia (30.77%),
      hypocalcaemia (25.17%). There were 93 newborns in the observed group, and 50 in
      the control one. Mean value of the measured body temperature was 35.9 degrees C.
      20 newborns (32.26%) had moderate hypothermia, and 73 newborns (67.74%) had mild
      hypothermia. In the observed group, average gestation was 39.0 weeks, and 39.6 (p
      < 0.01) in the control group. Average body mass at birth in the whole group was
      2339 g: 2214 g in the observed and 2571 g in the control group. The frequency of
      hypoglycaemia in the observed group was 53.8%, and 24% in the control group (p <
      0.01). In the observed group, the frequency of pH < 7.25 was 38.71%, and 14% in
      the control group (p < 0.05). The frequency of hyperbilirubinaemia was 38.71% in
      the observed group, and 16% in the control group (p < 0.01). The frequency of
      hypocalcaemia was 32.26% in the observed, and 12% in the control group (p <
      0.01). CONCLUSION: Transitory hypothermia in the first ten hours of life
      represents a significant risk factor for deepening hypoglycaemia, asphyxia,
      hyperbilirubinaemia and hypocalcaemia in term newborns with IUGR.

PMID- 21180091
TI  - [Neonatal hip dysplasia--differential diagnosis].
AB  - INTRODUCTION: Hip dysplasia is the elementary form of the developmental dysplasia
      of the hip (DDH). The diagnosis may be made by the ultrasound examination (types
      II a-, II b). OBJECTIVE: The aim of the authors was to define the congenital
      structural neonatal hip dysplasia, and to differentiate hip hypoplasia, hip
      dysplasia and teratogenic anomalies. METHODS: In all the cases, the uniform
      clinical and ultrasound tests were performed. All the patients were examined in
      the neonatal period of life (the first six weeks). The following clinical tests
      were used: Le Damany-Ortolany, Coleman-Barlow-Palmen and Weissman-Strinovic. For
      the ultrasound examination, the Graph's method was used. RESULTS: The
      investigation was performed in the period 2007-2008. 2,878 neonates were
      included. The distribution of the sonotypes, according to Graph, was as follows:
      Ia in 16.17%. Ib in 65.08%; IIa+ in 18.17%, IIc in 0.28%, IId in 0.19%; IIIa in
      0.009%, IIIb in 0.02%; and IV in 0.01%. It was found that DDH was 8 times more
      frequent in girls; located more frequently at the left side than bilaterally.
      CONCLUSION: Hip sonoscreening has to be performed in all newborns in the first 72
      hours. The suggested follow-up period is six weeks: for the diagnosis--the first
      three weeks, and for the prevention and treatment--all six weeks.

PMID- 21180092
TI  - [JAK2-V617F mutation in patients with myeloproliferative neoplasms: association
      with FLT3-ITD mutation].
AB  - INTRODUCTION: An acquired somatic mutation V617F in Janus kinase 2 gene (JAK2) is
      the cause of uncontrolled proliferation in patients with myeloproliferative
      neoplasms. It is known that uncontrolled myeloid cell proliferation is also
      provoked by alteration in other genes, e.g. mutations in receptor tyrosine kinase
      FLT3 gene. FLT3 represents the most frequently mutated gene in acute myeloid
      leukaemia. Interestingly, mutated FLT3-ITD (internal tandem duplication) protein
      is a member of the same signalling pathway as JAK2 protein, the STATS signalling
      pathway. STAT5 activation is recognized as important for self-renewal of
      haematopoetic stem cells. OBJECTIVE: The aim of this study was the detection of
      JAK2-V617F mutation in patients with myeloproliferative neoplasms. Additionally,
      we investigated the presence of FLT3-ITD mutation in JAK2-V617F-positive patients
      in order to shed the light on the hypothesis of a similar role of these two
      molecular markers in haematological malignancies. METHODS: Using allele-specific
      PCR, 61 patients with known or suspected diagnosis of myeloproliferative
      neoplasms were tested for the presence of JAK2-V617F mutation. Samples that were
      positive for JAK2 mutation were subsequently tested for the presence of FLT3-ITD
      mutation by PCR. RESULTS: Eighteen of 61 analysed patients were positive for JAK2
      V617F mutation. Among them, 8/18 samples were diagnosed as polycythaemia vera,
      and 10/18 as essential thrombocythaemia. None of JAK2-V617F-positive patient was
      positive for FLT3-ITD mutation. CONCLUSION: This study suggests that one
      activating mutation is sufficient for aberrant cell proliferation leading to
      malignant transformation of haematopoetic stem cell.

PMID- 21180093
TI  - [Descriptive analysis of work and trends in anaesthesiology from 2005 to 2006:
      quantitative and qualitative aspects of effects and evaluation of anaesthesia].
AB  - INTRODUCTION: In anaesthesiology, economic aspects have been insufficiently
      studied. OBJECTIVE: The aim of this paper was the assessment of rational choice
      of the anaesthesiological services based on the analysis of the scope,
      distribution, trend and cost. METHODS: The costs of anaesthesiological services
      were counted based on "unit" prices from the Republic Health Insurance Fund. Data
      were analysed by methods of descriptive statistics and statistical significance
      was tested by Student's t-test and chi2-test. RESULTS: The number of general
      anaesthesia was higher and average time of general anaesthesia was shorter,
      without statistical significance (t-test, p = 0.436) during 2006 compared to the
      previous year. Local anaesthesia was significantly higher (chi2-test, p = 0.001)
      in relation to planned operation in emergency surgery. The analysis of total
      anaesthesiological procedures revealed that a number of procedures significantly
      increased in ENT and MFH surgery, and ophthalmology, while some reduction was
      observed in general surgery, orthopaedics and trauma surgery and cardiovascular
      surgery (chi2-test, p = 0.000). The number of analgesia was higher than other
      procedures (chi2-test, p = 0.000). The structure of the cost was 24% in
      neurosurgery, 16% in digestive (general) surgery,14% in gynaecology and
      obstetrics, 13% in cardiovascular surgery and 9% in emergency room.
      Anaesthesiological services costs were the highest in neurosurgery, due to the
      length anaesthesia, and digestive surgery due to the total number of general
      anaesthesia performed. CONCLUSION: It is important to implement pharmacoeconomic
      studies in all departments, and to separate the anaesthesia services for
      emergency and planned operations. Disproportions between the number of
      anaesthesia, surgery interventions and the number of patients in surgical
      departments gives reason to design relation database.

PMID- 21180094
TI  - [Neuroborreliosis in patient with aplastic anaemia secondary to therapy with
      ticlopidine].
AB  - INTRODUCTION: Aplastic anaemia is a rare but potentially fatal complication of
      treatment with ticlopidine. CASE OUTLINE: We present a 55-year-old male with
      aplastic anaemia which developed after 45 days of the therapy with 200 mg
      ticlopidine to prevent coronary thrombosis. The treatment with ticlopidine was
      withdrawn and broad spectrum antibiotics as well as transfusion of packed red
      cells, platelets and G-CSF were administered. Two weeks after the onset of the
      disease, the number of white blood cells dropped to 0.5 x 10(9)/l, along with
      drop of both haemoglobin concentration and the number of platelets. At that time,
      weakness of facial muscles due to bilateral facial nerve paralysis with Bell's
      phenomenon and after that weakness of muscles of both legs and signs of
      polyradiculoneuritis were developed. Western blot analysis of blood and liquor
      showed a high concentration of IgG and IgM antibodies against Borrelia
      burgdorferi. The treatment with cephtriaxone resulted in normalization of body
      temperature and gradual recovery of neurological findings. Blood picture became
      normal two months after the onset of the disease. CONCLUSION: The treatment with
      ticlopidine may result in different haematological complications such as
      agranulocytosis/ granulocytopaenia, thrombotic trombocytopenic purpura and rarely
      aplastic anaemia. Due to these complications blood pictures in patients on this
      therapy should be closely followed up and in case of complications, the treatment
      with ticlopidine has to be stopped and introduce the therapeutic procedures
      depending on the sort of the complications and clinical presentation.

PMID- 21180095
TI  - [Pseudopacemaker syndrome and marked first-degree atrioventricular block: case
      report].
AB  - INTRODUCTION: Pacemaker syndrome consists of the symptoms and signs present in
      the single chamber (VVI) pacemaker patient with electrode placed in the right
      ventricular apex. It is caused by inadequate timing of atrial and ventricular
      contractions. Pacemaker syndrome without a pacemaker (or pseudopacemaker
      syndrome) refers to occurrence of symptoms in the presence of marked first-degree
      atrioventricular (AV) block, when P wave is too close to the preceding QRS
      complex producing the same haemodynamic disturbance as artificial pacemaker
      cardiac stimulation with retrograde VA conduction. CASE OUTLINE: We present the
      patient with acute inferior myocardial infarction due to late bare metal stent
      thrombosis, treated with primary pectutaneous coronary intervention. Hospital
      course was complicated by complete heart block which was treated with temporary
      pacing. During the stand-by mode of temporary pacing, sinus rythm with marked
      first-degree AV block (PQ interval 480 ms) was observed while the patients re
      experienced the symptoms that were present prior to pacemaker implantation.
      Temporary pacing was continued for the next 24 hours when spontaneous shorteninig
      of PQ interval (250-270 ms) was noticed; since the patient was asymptomatic
      during the stand-by mode, the pacemaker electrodes were removed and the patient
      discharged 11 days after admission. CONCLUSION: Conduction disturbances, such as
      the varying degrees of AV blocks, are relatively common in acute inferior
      myocardial infarction. The first degree AV blok is usually asymptomatic and does
      not require treatment, unless when it is associated with pseudopacemaker
      syndrome. In that case, temporary pacing provides haemodynamic stability until
      conduction system recovers.

PMID- 21180096
TI  - [Pre-excitation pattern associated with accessory pathway related tachycardia:
      case report].
AB  - INTRODUCTION: Pre-excitation is based on an accessory conduction pathway between
      the atrium and ventricle. The term Wolff-Parkinson-White (WPW) syndrome is used
      for patients with the pre-excitation/WPW pattern associated with AP-related
      tachycardia. CASE OUTLINE: We present a 52-year-old man with severe palpitation,
      fatigue, lightheadedness and difficulty breathing. The initial ECG showed
      tachyarrhythmia with heart rate between 240 and 300/min. He was treated with
      antiarrhythmics (Digitalis, Verapamil, Lidocaine) with no response. Then, the
      patient was treated with electrical cardioversion and was referred to our Clinic
      for further evaluation with the diagnosis: "Ventricular tachycardia". During in
      hospital stay, the previously undiagnosed WPW pattern had been seen. Additional
      diagnostic tests confirmed permanent pre-excitation pattern (ECG Holter
      recording, exercises test). The patient was referred to an electrophysiologist
      for further evaluation. Mapping techniques provided an accurate assessment of the
      position of the accessory pathway which was left lateral. The elimination of the
      accessory pathway by radiofrequent catheter ablation is highly effective in
      termination and elimination of tacchyarrhythmias. CONCLUSION: Symptomatic, life
      threatening arrhythmia, first considered as ventricular tachycardia, reflected
      atrial fibrillation with ventricular pre-excitation over an accessory pathway in
      a patient with previously undiagnosed WPW syndrome.

PMID- 21180097
TI  - [Treatment of septic pseudoarthrosis of tibia by Ilizarov method: case report].
AB  - INTRODUCTION: Septic pseudoarthroses of the tibia represent a relatively frequent
      complication of open fractures with a large soft tissue damage. They may be
      localized: in the proximal metaphysis, between the proximal and middle thirds,
      between middle and distal thirds, in the distal metaphysis. CASE OUTLINE: A case
      of a 52-year-old man with open fracture of the left tibia is presented. He fell
      from the height of 30 meters. The external fixation according to Mitkovic was
      performed in another institution. The patient was referred to our hospital nine
      months after the accident, with clear clinical and radiological signs of septic
      pseudoarthrosis of the tibia. The resection of septic pseudoarthrosis was done
      two weeks after admission. Three weeks later, another operation was performed,
      bilocal alternating distractive-compressive osteosynthesis according to Ilizarov.
      After eleven months Ilizarov frame was removed, with clinical, radiological signs
      of healing of pseudoarthrosis and complete curing of the infection. Five months
      after removal of the frame, the patient was fully anatomically and functionally
      recovered. CONCLUSION: Being satisfied with the achieved results and encouraged
      with the data from the literature, we recommend this method as the method of
      choice for the treatment of pseudoarthrosis of the tibia. The advantage consists
      of curing the infection using the natural bactericide power of the tissue and
      curing the bone defect, at the same time, and finally, producing the equalization
      of the legs.

PMID- 21180098
TI  - [Mother's filicide with suicide attempt].
AB  - INTRODUCTION: Filicide is the killing of a son or daughter by a parent. The paper
      examines interaction between stress and maternal psychopathology that led to the
      killing. CASE OUTLINE: After prolonged conflict with her ex-husband and father of
      her only child, the respondent committed filicide. Two years before committing
      filicide, after she had divorced the father of the child, the respondent
      attempted suicide and had to be hospitalized. On that occasion, she was diagnosed
      with depressive disorder, which was not treated after hospitalization. Having
      killed her daughter by cutting her throat, she tried to commit suicide in the
      same manner, by slitting her throat. During further observation, the respondent
      was found to suffer from acute psychotic disorder, depressive disorder and
      histrionic personality disorder. These disorders in interaction with stress do
      not provide us with an explanation for an unusual and psychopathological
      motivation analysis of killing the child. CONCLUSION: Filicide is a violent act,
      most frequently multifactorial in its nature. Histrionic personality disorder in
      mother cannot explain the filicide act. Only interactive and dynamic evaluation
      of this psychiatric disorder in its longitudinal, development aspects and its
      potentiality to enable the expression of some other psychiatric disorders,
      especially dissociative states, as well as the importance of prolonged and acute
      stress and its subjective importance for the individual can shed some more light
      on the mental state of the mother at the time of filicide.

PMID- 21180099
TI  - [Antiphospholipid syndrome in neurology].
AB  - Antiphospholipid syndrome (APS) is an autoimmune disease with recurrent
      thromboses and pregnancy complications (90% are female patients) that can be
      primary and secondary (with concomitant autoimmune disease). Antiphospholipid
      antibodies are prothrombotic but also act directly with brain tissue. One
      clinical and one laboratory criterion is necessary for the diagnosis of APS.
      Positive serological tests have to be confirmed after at least 12 weeks. Clinical
      picture consists of thromboses in many organs and spontaneous miscarriages,
      sometimes thrombocytopaenia and haemolytic anaemia, but neurological cases are
      the most frequent: headaches, stroke, encephalopathy, seizures, visual
      disturbances, Sneddon syndrome, dementia, vertigo, chorea, balism, transitory
      global amnesia, psychosis, transversal myelopathy and Guillain-Barre syndrome.
      About 50% of strokes below 50 years of age are caused by APS. The first line of
      therapy in stroke is anticoagulation: intravenous heparin or low-weight heparins.
      In chronic treatment, oral anticoagulation and antiplatelet therapy are used,
      warfarin and aspirin, mostly for life. In resistant cases, corticosteroids,
      intravenous immunoglobulins and plasmapheresis are necessary. Prognosis is good
      in most patients but some are treatment-resistant with recurrent thrombotic
      events and eventually death.

PMID- 21180100
TI  - [Pelvic inflammatory disease: contemporary diagnostic and therapeutic approach].
AB  - Pelvic inflammatory disease (PID) is polymicrobial infection in women
      characterized by inflammation of the upper genital tract, including endometritis,
      salpingitis, pelvic peritonitis, occasionally leading to the formation of tubo
      ovarian abscess (TOA). PID primarily affects young, sexually active women, and it
      is highly correlated with having several sexual partners, intrauterine
      contraceptive device and sexually transmitted diseases. The spectrum of disease
      is caused most commonly by Chlamydia trachomatis and Neisseria gonorrhoeae in 30
      50% of cases. PID is responsible for severe acute morbidity and significant long
      term sequelae, including tubal factor infertility, ectopic pregnancy, and chronic
      pelvic pain. The following clinical features are suggestive of a diagnosis of
      PID: bilateral lower abdominal tenderness, abnormal vaginal or cervical
      discharge, fever (higher than 38 degrees C), abnormal vaginal bleeding,
      dyspareunia, cervical motion tenderness and adnexal tenderness, with or without a
      palpable mass. In laboratory findings, there is presence of excess leucocytes,
      elevated erythrocyte sedimentation rate or C-reactive protein. Transvaginal
      ultrasound scanning may be helpful, and its sensitivity is up to 85%. It can
      identify inflamed and dilated tubes and tubo-ovarian masses. Magnetic resonance
      imaging can be helpful in a final diagnosis in 95% of cases. In 15-30% of
      suspected cases, there is no laparoscopic evidence of disease. Treatment regimens
      for PID include broad-spectrum antibiotics, including coverage for Neisseria
      gonorrhoeae and Chlamydia trachomatis. The usage of parenteral or oral therapy,
      inpatient or outpatient regimens, depends on the patient's clinical condition.
      Considering the potential complications of disease, there is a need for good
      health educational programmes in reproductive period.

PMID- 21180101
TI  - [Social aspects of left-handedness].
AB  - Throughout human history left-handedness has been considered as sinful. It has
      been associated with the devil, weakness, female gender, unhealthiness, evil,
      something that has to be turned to a "good"--right side by force. Left-handedness
      is being more and more acceptable at rational level, but in everyday life it is
      still considered to be unusual if someone writes with the left hand. Lessening of
      the number of lefthanders is associated with ageing. There are about 13%
      lefthanders among people in twenties and less than 1% lefthanders among those in
      eighties. This finding may be explaned with more pronounced socio-cultural
      pressure on left-handed people in the past, compared to nowadays. On the other
      hand, this may also support the hypothesis about a reduced life span of
      lefthanded people. With cross-exercising of left-handedness, certain typical
      characteristics and behavioural patterns appear in these people. This was a sort
      of provoked behaviour and an attack on the integrity of an emotional attitude
      toward oneself. Stuttering may also appear as a consequence of unsuccessful cross
      exercising of left-handedness. The hypothesis about left-handedness as an
      advantage is supported with the reports about relatively more lefthanders in some
      specific groups such as: mathematicians, sculptors, architects, painters,
      musicians, actors, tennis players, as well as famous army commanders and rulers.

PMID- 21180102
TI  - [Specific features of written medical English language].
AB  - Medical language is a special language used by experts in mutual communication.
      One of the characteristics of medical discourse community is writing research
      papers in English. When writing a research paper, it is necessary to apply
      appropriate rules based on the IMRAD structure. This structure has its own
      clearly defined style which is clear, precise, exact and objective. This style of
      writing reflects the characteristics of medical language. The most frequent
      problems that doctors encounter in this context predominantly refer to linguistic
      elements of English. Namely, a very common dilemma is related to the use of
      English tenses in specific parts of the IMRAD structure. Another problem is the
      use of specific expressions for introducing a research, presenting results and
      methods used, developing discussion and stating conclusions. This work aims to
      point out the specific style and structure of medical research papers in English
      with an outline of the linguistic elements used in this context.

PMID- 21180103
TI  - [Application of hair analysis of selected psychoactive substances for medico
      legal purposes. Part II. Cases of complex fatal poisonings: interactions of
      heroine - cocaine - amphetamines].
AB  - The study represents an attempt at employing segmental hair analysis in complex
      poisonings with xenobiotic mixtures of heroine - cocaine - amphetamines in the
      context of the cause of death as a consequence of complex interaction mechanisms
      which occurred prior to death. Two cases of complex poisonings: heroine - cocaine
      and heroine - cocaine - amphetamines were analyzed and documented with macro- and
      microscopic examinations and complex toxicological examinations, including the
      analysis of classic biological material, i.e. samples of selective blood, and
      alternative material, i.e. hair samples. Determinations of opioids, cocaine and
      its metabolite and amphetamines in the hair biological matrix were performed
      using high performance liquid chromatography--atmospheric pressure chemical
      ionization--tandem mass spectrometry (HPLC-APCI-MS-MS). Segmental hair analysis
      of the investigated cases indicated a prolonged intake of similar psychoactive
      substances and a developed adaptation of the addicted to interaction mechanisms,
      which, however, led gradually to multiorgan anatomopathological changes, and in
      consequence to death.

PMID- 21180104
TI  - [Pulmonary microscopic lesions in drug addicts--a preliminary report].
AB  - BACKGROUND: A sudden death of drug addicts is generally attributed to the
      depressive effect of substances in question on the respiratory center in the CNS.
      Microscopic morphology of lungs is relatively rarely dealt with. PURPOSE: This
      study probes into the morphology of individuals who were intoxicated by
      amphetamine and/or heroin and suddenly died. MATERIAL AND METHODS: The
      investigated group comprised lung specimens collected in the files of the
      Department of Forensic Medicine of Medical University of Warsaw in the years 2002
      2004. A total of 41 autopsied drug addicts suddenly succumbed without any medical
      intervention. Formol-fixed paraffin blocks were stained with HE. The presence of
      opiates and/or amphetamine was investigated in body fluids at autopsy and
      recorded. The control group of 50 non-addicts originated from the files of the
      Department of Pathomorphology of the Rheumatologic Institute of Warsaw.
      Immunohistochemistry for alpha-1-antitripsin was performed in both groups.
      RESULTS: The microscopic image of the lungs in the investigated group showed a
      pronounced hyperemia of the thickened interalveolar septa. The alveoli and
      alveolar ductules were enormously expanded by fluid, which contained numerous air
      bubbles of variable, rather striking sizes. The fluid showed multiple hemosiderin
      loaded macrophages. The reaction for alpha-1-antitripsin was negative. Microscopy
      of the lungs from the control group failed to demonstrate any essential
      abnormalities. The reaction for alpha-1-antitripsin was positive. CONCLUSIONS:
      Microscopy of the lungs of drug addicts is characteristic and attributed to drug.
      The pathologist facing such a picture is obliged to review and discuss with the
      clinician the possibility of drug addiction, if it has not been indicated so far.
      The investigation into the contribution of alpha-1 -antitripsin deficit should be
      continued.

PMID- 21180105
TI  - [Identification of a murderer on the basis of a biting pattern on body of the
      victim].
AB  - The authors present a case of identification of a a murderer on the basis of his
      dentition pattern, reflected by a biting wound on the breast of the victim. The
      case is exceptional not only from the viewpoint of the authors, but also in view
      of very sporadic reports on this subject in forensic literature. Cases of biting
      by humans are not frequent in the forensic/ medical practice, and instances of
      identification of the perpetrator by his dental pattern reflected in the biting
      wound are very rare. In Poland, such problems have been the domain of mainly
      criminologists and only occasionally of forensic medics in collaboration with
      dentists and anthropologists. Due to the very low number of such cases in Poland,
      no experts in the matter are available. For this reason, we deemed it purposeful
      to present respective investigative principles and techniques for identification
      of a human perpetrator on the basis of the dental pattern reflected in a biting
      wound on the victim's body.

PMID- 21180106
TI  - [Usefulness of preliminary evaluation of postmortem CT as an extension of
      diagnostic capabilities of conventional forensic autopsy].
AB  - Based on material from their studies, the authors discuss how the initial
      evaluation of data obtained through the acquisition of postmortem CT prior to
      autopsy may point to traumatic changes that could be difficult to find in
      conventional medico-legal autopsy.

PMID- 21180107
TI  - [Value of postmortem CT examinations in cases of extensive mechanical injuries
      causing considerable corpse destruction].
AB  - The authors present three-dimensional reconstructions based on acquisition of
      postmortem CT examinations in cases of extensive mechanical injuries. The data
      may be helpful in identification of the examined fragment of the body, as well as
      useful for further analysis of the mechanism of injuries. An additional aspect of
      the analyzed data refers to possible obtaining information that may confirm the
      identity of the deceased.

PMID- 21180108
TI  - [The evolution of autopsy technique--from Virchow to Virtopsy].
AB  - The autopsy technique evolves with extending knowledge and technical and
      technological progress in medical sciences. The objective of this report is to
      present the main autopsy techniques and an outline of transformations that
      occurred in the methodology of post mortem examinations with a focus on the
      Polish literature. Additionally, we present examples of paintings inspired by
      autopsy.

PMID- 21180109
TI  - [Polish forensic entomology--the past, present and future perspectives].
AB  - Forensic medicine increasingly more often benefits from the achievements of other
      biological sciences, which may be used in post mortem investigation. One of them
      is forensic entomology--the science based on the knowledge about biology of
      insects preying on cadavers. The objective of this article is to present the
      history of Polish forensic entomology, its present state and possibilities and
      directions of further development.

PMID- 21180110
TI  - [Medico-legal autopsy--selected legal issues: regulation concerning the
      performance of medico-legal autopsy of July 15, 1929].
AB  - Polish literature on law and forensic pathology abounds with opinions that the
      Regulation of the Minister of Justice and of the Minister of Internal Affairs
      Concerning the Performance of Medico-Legal Autopsy of 15 July 15, 1929, continues
      to remain in force. The authors thoroughly analyse the provisions of the Criminal
      Procedure Code of 19 April, 1969 and the Act on Enactment of the Provisions of
      the Criminal Procedure Code of 19 April, 1969. The results of semiotic and
      systematic interpretations of the aforementioned acts leave no doubt that the
      regulation of 1929 has been derogated. Nonetheless, the authors stress that,
      despite the lack of legal force, the regulation of the interwar years can still
      be considered a useful guide for less experienced doctors who perform medico
      legal autopsies on an ad hoc basis.

PMID- 21180111
TI  - [Medico-legal autopsy--selected legal issues: the autopsy protocol].
AB  - The majority of experts in the field of forensic medicine maintain that the
      minutes of the medicolegal autopsy should be taken by the forensic pathologist.
      The authors argue that it is the public prosecutor who is obliged to draw up the
      minutes, whereas the forensic pathologist issues the expert opinion. To support
      their stance, the authors make frequent references to several provisions of the
      Criminal Procedure Code of 1997. The authors also imply that due to
      organizational reasons and the ratio legis of the aforementioned code, the
      forensic pathologist should not be assigned the role of the minutes-taker,
      despite the lack of a specific exclusion rule governing such a case. Possible
      consequences caused by the lack of the properly drawn up minutes are briefly
      discussed as well.

PMID- 21180112
TI  - [Effect of intestinal lymphatic pathway on free radical and inflammatory mediator
      of myocardium in shock rats].
AB  - AIM: To observe the effect of mesenteric lymph duct ligation on free radical and
      inflammatory mediator of myocardium with severe hemorrhagic shock in rats at
      different period, and explore the effect of intestinal lymphatic pathway on
      myocardium injury pathogenesis in shock rats. METHODS: 78 male Wistar rats were
      divided into the sham group, shock group and ligation group. The model of serious
      hemorrhagic shock was established in shock group, ligation group, and mesenteric
      lymph was blocked by ligating mesenteric lymph duct in ligation group after
      resuscitate. All rats were executed and taken out heart making for homogenate of
      10 percent to determine the MDA, SOD, tumor necrosis factor-alpha (TNFalpha),
      interleukin-6 (IL-6), myeloperoxidase (MPO), NO and NOS at after shock 90 min,
      after transfusion and resuscitate 0 h, 1 h, 3 h, 6 h, 12 h and 24 h etc.
      different times, and the expression of inducible nitric oxide synthase (iNOS)
      mRNA in myocardium was detected by RT-PCR. RESULTS: The contents of MDA,
      TNFalpha, IL-6, MPO, NO, NOS and iNOS expression in myocardium of shock group
      were rising after transfusion and resuscitate, and that was higher level at 3 h
      to 12 h, and that was significantly higher than sham group, the activity of SOD
      was significantly lower than sham group. The contents of MDA, TNFalpha, IL-6,
      MPO, NO, NOS and iNOS expression in myocardium of ligation group were
      significantly lower than that of shock group at sameness points, and the SOD
      activity was higher. CONCLUSION: The mesenteric lymph duct ligation and blocking
      mesenteric lymph could reduce the PMN detaining, decrease the discharging of TNFa
      and IL-6, reduce the NO and expression of iNOS mRNA, and reduce the releasing of
      free radical and consuming of SOD.

PMID- 21180113
TI  - [Assessment of cardiac structure and function by echocardiographic values for
      male Balb/c mice].
AB  - AIM: To assess the parameters of cardiac structure and function of male Balb/c
      mice by the echocardiography. METHODS: A total of 27 male Balb/c mice (from five
      to seven week old) were examined with a 13-MHz transthoracic linear-array
      transducer, hearts were removed from mice anesthetized with Nembutal, and the
      left ventricular (LV) mass were weighed. RESULTS: Complete 2-dimensional
      echocardiography for cardiac structure and function were obtained. Hemodynamic
      parameters were recorded. A correlation existed between LV weight (x) and
      echocardiographic LV mass (y) with the 2D) guided M-mode method: y = 1.15x +
      3.26, (r = 0.80). CONCLUSION: Echocardiography appears to be a promising approach
      for noninvasively assessing LV mass and function in mice.

PMID- 21180114
TI  - [Effect of PAF on the expression of PACAP mRNA in the granulosa cells of rat
      ovary].

PMID- 21180115
TI  - [Study on calcium-activated potassium channel of mesentery artery smooth muscle
      cells of hypertension patients].
AB  - AIM: To study the functional activity of K(cA) on human mesenteric artery smooth
      muscle cells (SMC) from essential hypertension (EH) patients. METHODS: Patch
      clamp technique with Inside-out mode was used for recording channel activity.
      RESULTS: (1) K(CA) from human mesenteric artery SMC was voltage dependent. Single
      channel conductance was 191.4 pS and 197.7 pS in EH group and normal group
      respectively. The channel activity was blocked by TEA in cytoplastic side. (2)
      With the increasing of Ca2+ concentration in the bath solution (fron 0 to 10(-8),
      10(-7), 5 x 10(-7), 10(-6) mol/L), the K(Ca) channel open probability (Po) of two
      groups were increased, Po of EH group increased from 0.016 to 0.023, 0.031,
      0.0153, 0.094, Po of normal group increased from 0.004 to 0.023, 0.041, 0.072,
      0.184. The mean open time lengthened and the mean close time shortened. (3) Po of
      K(Ca) of EH group was higher than that of normal group when Ca2+ concentration
      was 0, but it was equal with or lower than normal group at the other Ca2+
      concentrations. CONCLUSION: K(Ca) of mesenteric artery SMC from EH group has a
      lower Ca2+ sensitivity than that of normal person. This might be an active factor
      for the onset of EH.

PMID- 21180116
TI  - [Experimental studies on antiarrhythmic effect of jumi extraction].
AB  - AIM: To investigate the antiarrhythmic effect of jumi (JM) extraction. METHODS:
      The conventional antiarrhythmic methods were used. RESULTS: Administration of JM
      extraction reduced the occurrence of ventricular fibrillation induced by
      chloroform in a dose-dependent manner in mice. Quinidine significantly decreased
      the number of ventricular premature beats and ventricular tachycardia, shortened
      the duration of arrhythmia in aconitine-treated rats. But JM extraction had no
      effect on aconitine-induced arrhythmia. Compared with control, arrhythmia score
      was lower in ischemia/reperfusion rats which pretreated with 2.0 g/kg of JM
      extraction. CONCLUSION: JM extraction has obvious protection effects in
      chloroform- and ischemia-induced arrhythmia, but has no effect in aconitine
      induced arrhythmia.

PMID- 21180117
TI  - [Effect of allicin on hippocampal neuronal apoptosis induced by globe cerebral
      ischemia/reperfusion].

PMID- 21180119
TI  - [The effects of endurance exercise on NOS activity in hyperlipidemia mice].

PMID- 21180118
TI  - [Electrophysiological effect of levofloxacin on ventricular myocytes in guinea
      pig].
AB  - AIM: To learn the electrophysiological interference of levofloxacin (LVFX) to
      heart in guinea pig. METHODS: High, moderate and low doses of LVFX were given to
      the anesthetic guinea pig via i.p., and QT interval span and corrected QT
      interval span in the II leading lines of ECG were recorded and analyzed from 5
      min to 360 min after the drug administration. Single ventricular myocytes were
      obtained and impacted by LVFX solution of different concentrations. Then delayed
      rectifier potassium currents (I(K)) on single cells were recorded with whole-cell
      patch clamp technique, and compared with control group(without impact of LVFX).
      RESULTS: (1) After the administration of LVFX, at the dose of 200 mg/kg. QT
      interval span was significantly elongated, and the increasing rate is 19.38% +/-
      3.15% (P < 0.05). While at the relatively lower doses of 50 mg/kg and 100 mg/kg,
      the elongation is of low/no significance (P > 0.05). (2) LVFX inhibited I(K) dose
      dependently and time-dependently. CONCLUSION: LVFX might prolong the QT-interval
      span by the mechanism of inhibiting I(K), which implies a potential risk in
      clinical application.

PMID- 21180120
TI  - [Effects of overexpression of beta2-adrenoceptor on contraction in cardiac
      myocytes isolated from failure hearts of rats].
AB  - AIM: To investigate the role of overexpression of beta2-adrenoceptor on
      contraction in cardiac myocytes isolated from failure hearts of rats and
      primarily analyses its mechanisms. METHODS: Primarily cultured cardiac myocytes
      were infected with adenovirus containing the sequence for human beta2
      adrenoceptors. The expression of beta2-adrenoceptors was tested by Western blot.
      The contraction amplitudes induced by isoprenaline stimulation were measured.
      RESULTS: Overexpression of beta2-adrenoceptor increased the content in failure
      cardiac myocytes. The contraction amplitudes in failure cardiac myocytes were
      lower than that in the control (P < 0.01). Overexpression of beta2 adrenoceptor
      improved the contraction of failure cardiac myocytes (P < 0.01, Failure+
      Adv.Beta2 group vs. Failure group). Selective beta2-adrenoceptor antagonist ICI
      118,551 partially reversed the effects (P < 0.05, Failure+ Adv.beta2 + ICI group
      vs Failure + Adv.beta2 group), but the contraction amplitudes in this Failure +/-
      Adv.beta2 + ICI 118,551 group were still higher than that in only heart failure
      group (P < 0.05). Selective beta1 adrenoceptor antagonist CGP20712A completely
      inhibited the effects of overexpression of beta2 adrenoceptor on contraction
      amplitude in failure cardiac myocytes. CONCLUSION: Overexpression of beta2
      adrenoceptors improves the contraction of cardiac myocytes isolated from failure
      hearts of rats. The effect is related to beta1-adrenoceptor.

PMID- 21180121
TI  - [Effects of omapatrilat on endothelin-1-induced proliferation and synthesis of
      cardiac fibroblasts].
AB  - AIM: To investigate the effects of omapatrilat (OMA) on endothelin-1-induced
      proliferation of cardiac fibroblasts (CFs). METHODS: Isolated and cultured CFs
      from neonatal Sprague-Dawley rats (SD) were randomly divided into 7 groups: (1)
      Control, (2) ET-1, (3) OMA, (4) ET-1 + OMA 10(-9) mol/L, (5) ET-1 + OMA 10(-8)
      mol/L, (6) ET-1 + OMA 10(-7) mol/L and (7) ET-1 + OMA 10(-6) mol/L. CFs were
      counted by MTT assay. Cell cycle distribution was determined with a flow
      cytometer (FCM). [3H]-Proline incorporation was evaluated by scintillation
      counting. Nitric oxide (NO) was measured by colorimetry. RESULTS: 10(-7) mol/L ET
      1 significantly increased A490 value and [3H]-Pro incorporation and decreased NO
      secretion compared with the control group (P < 0.01). 10(-9)-10(-6) mol/L OMA
      inhibited the effects of ET-1 on CFs in a concentration-dependent manner (P <
      0.01 vs. ET-1). In the ET-1 group, the percentage of cells in the S phase was
      higher than control, which was inhibited by l0(-6) mol/L OMA (P < 0.01 vs. ET-1
      and control). CONCLUSION: OMA can restrain the proliferation and collagen
      synthesis of cardiac fibroblasts induced by endothelin-1, and this effect may be
      partially mediated by NO.

PMID- 21180122
TI  - [Distribution and expression of p38 MAPK in the distal cerebrospinal fluid
      contacting neurons in brain of rat by noise stress].
AB  - AIM: To observe the distribution and expression of p-p38MAPK in the distal
      cerebrospinal fluid contacting neurons in brain of rat by noise stress. METHODS:
      By a double-labelled method combing the tracing of CB-HRP and the
      immunohistochemical technique p-p38MAPK, the distribution and expression of p
      p38MAPK in the distal cerebrospinal fluid contacting neurons(csf cn) were
      observed following noise stress. Expression of p-p38MAPK and double-labelled of
      CB-HRP/p-p38MAPK were also observed in rat brain after noise stress. RESULTS: Two
      groups of CB-HRP labeled neuron clusters consistently appeared in certain regions
      of the brainstem but none in other regions of the brain. Without noise stress
      exposure, only a few neurons were found double-labeled by CB-HRP/p-p38MAPK. After
      1 day noise stress exposure, only few neurons double-labeled by CB-HRP/p-p38MAPK
      were observed in the above-mentioned regions. After 5 days, the number of neurons
      double-labeled by CB-HRP/p-p38MAPK increased significantly compared with the
      control group (P < 0.05). After 10 days, the number of neurons double-labeled by
      CB-HRP/p-p38MAPK increased significantly compared with the control group (P <
      0.05). After 20 days, both of the numbers of neurons double-labeled by CB-HRP/p
      p38MAPK increased significantly compared with that of the control group (P <
      0.01). CONCLUSION: Two groups of distal cerebrospinal fluid contacting neuron
      clusters consistently existed in certain regions of the brain parenchyma, and in
      these clusters only a few neurons con rained p-p38MAPK. After noise stress
      exposure of different durations (days 1, 5, 10, 20), the number of distal
      cerebrospinal fluid contacting neurons with p-p38MAPK increased significantly
      with increasing days. The results indicate that distal cerebrospinal fluid
      contacting neurons are special neurons existing consistently in brain, including
      distal cerebrospinal fluid contacting neurons with p-p38MAPK which may
      participate in the whole procedure of signal transduction or central modulation
      in noise stress response and play greater roles with increasing days.

PMID- 21180123
TI  - [Cyclical theta oscillation induced by acute weak electrical stimulation of the
      rat vagus nerve central end].

PMID- 21180124
TI  - [The protective effect of nicotine on dopaminergic neuron of Parkinson's disease
      mice].
AB  - AIM: To investigate the protective effect of nicotine on dopaminergic neurons and
      its mechanisms in mice with Parkinson's disease (PD) induced by 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP). METHODS: C57BL/6J mice were injected with MPTP
      for 8 days to establish PD model. Nicotine was given for 10 days in the
      pretreatment group. Animals were examined behaviorally with the pole test and
      traction test. Tyrosine hydroxylase (TH) and gamma-aminobutyric acid (GABA) were
      investigated by the immunocytochemistry (ICC) method. The ultrastructural changes
      of caudate nucleus(CN) were observed by electron microscope. RESULTS: The results
      showed that pretreatment nicotine could improve the dyskinesia of PD mice
      markedly. Simultaneously, TH (P < 0.01) neurons and GABA (P < 0.05) neurons were
      much more in the pretreatment group when compared with those in the model group.
      The ultrastructural injury of the pretreatment group was also ameliorated.
      CONCLUSION: Nicotine has a protective effect on the dopaminergic neurons in the
      MPTP-treated mice.

PMID- 21180125
TI  - [Expression of HIF-1alpha induced by ginkgolides in primary cultured cortical
      neurons and the relationship with ERK signal pathway].
AB  - AIM: To study the effects of ginkgolides (Gin) on the expression of hypoxia
      inducible factor-1alpha (H1F-1alpha) in primary cultured cortical neurons treated
      with CoCl2 and the relationship with ERK signal pathway. METHODS: We observed the
      effects of Gin (37.5 mg/L) on morphology and viability on primary cultured
      cortical neurons with treatment of CoCl2 (125 micromol/L). The expression of HIF
      1alpha and p-ERK of neurons induced by CoCl2 pretreated with Gin were assessed by
      Western-blot. We analyzed the relationship between HIF-1alpha expression
      activated by Gin and ERK signal pathway with treatment of PD98059 (100
      micromol/L), a selective inhibitor of ERK. RESULTS: It was shown that Gin had
      protective effects on CoCl2 damaged neurons by raising the neuronal viability.
      Some basic expression of HIF-1alpha and p-ERK were observed in normal cultured
      cortical neurons. The expression of HIF-1alpha and p-ERK increased strikingly
      when treated with CoCl2 for 4 h. The levels of HIF-1alpha and p-ERK increased
      even more in the neurons pretreated with Gin for 24 h before CoCl2. The levels of
      HIF-1alpha and p-ERK were notably inhibited with pretreatment of PD98059, while
      Gin could prevent this inhibition. CONCLUSION: Gin has protective effects on
      neurons damaged by CoCl2 which might be related to the increase of the level of
      HIF-1alpha and the activation of ERK signal pathway.

PMID- 21180126
TI  - [Effects of chronic hypoxic hypercapnia on spatial learning-memory and expression
      of NMDAR1 in rats].
AB  - AIM: To explore the effect of chronic hypoxic hypercapnia on learning-memory and
      the possible mechanisms involved. METHODS: Fifty-eight male SD rats were randomly
      divided into three groups: Normal control group (NC, n=18), 2-week (2HH, n=18),
      and 4-week hypoxic hypercapnia (4HH, n=20) group. The rats, spatial learning
      memory tasks were assessed by the Morris water maze. The expression of NMDAR1mRNA
      was determined by hybridization in situ. RESULTS: Compared with NC group, rats
      exposed to chronic hypoxic hypercapnia displayed significant impairment in their
      performance assessed by two measures: mean escape latencies (2HH: 38.59 +/- 8.35
      s, 4HH: 60.59 +/- 17.28 s) and swim path distances(2HH: 9893.45 +/- 1958.16 mm,
      4HH: 18077.57 +/- 6878.85 mm). The expression level of NMDAR1mRNA in the
      hippocampus and cortex were lower than those in the NC group, especially, the
      NMDAR1mRNA expression of hippocampus CA1 in 4HH decreased by 21.4% (P < 0.01).
      CONCLUSION: Chronic hypoxic hypercapnia could impair the rat spatial learning
      memory and the decrease in expression of NMDAR1mRNA might be involved in.

PMID- 21180127
TI  - [The protective effects of group I mGluRs antisense oligonucleotides against
      neurotoxicity of sodium glutamate on cultured mouse cerebral cortical neurons].
AB  - AIM: To investigate the protective effect of mGluR1 antisense oligonucleotides
      and mGluR5 antisense oligonucleotides on impairment of cultured mouse cerebral
      cortical neurons induced by sodium glutamate (Glu). METHODS: Neuron damage
      induced by Glu as well as the action of mGluR1 antisense oligonucleotides and
      mGluR5 antisense oligonucleotides were measured by determining the leakage of
      lactate dehydrogenase (LDH) from neurons. Immunocytochemistry method was used to
      detect the expression of anti-mGluRl a and anti-mGluR5. Morphological changes of
      primary cortical neurons were observed by phase contrast microscope. RESULTS:
      Following the exposure of the cells to 0.1 mmol x L(-1) Glu for 15 min, LDH
      leakage from neurons increased. mGluR1 antisense oligonucleotides and mGluR5
      antisense oligonucleotides(6 or 8 micromol x L(-1)) as well as 50 micromol x L(
      1) LY367385 reduced the LDH leakage. mGluR1alpha and mGluR5 immunopositive cells
      showed in cultured neurons. CONCLUSION: The protective effects of mGluR1
      antisense oligonucleotides and mGluR5 antisense oligonucleotides on neurons
      damaged by Glu may relate to antagonizing mGluR1a or mGItlR5.

PMID- 21180128
TI  - [Effects and possible mechanism of cocaine on the neurons of lateral habenular
      nucleus].
AB  - AIM: To investigate the effects and the possible mechanism of cocaine on the
      neurons of lateral habenular nucleus (LHb). METHODS: We observed the effects on c
      Fos protein expression in lateral habenular nucleus and medial habenular nucleus
      after injecting cocaine into a belly cavity and spontaneous and evoked discharge
      of pain-correlative unit through iontophoresis of cocaine into LHb. The delayed
      rectifier K+ current was recorded in the acute isolated LHb neuron in whole-cell
      mode. RESULTS: (1) The c-Fos protein expression was increased by cocaine
      treatment in LHb, but little effect in MHb. (2) Iontophoresis of cocaine into LHb
      increased the discharges of pain excitation unit and enhanced excitation response
      to noxious stimulation, but it decreased the discharges of pain inhibition unit
      and its responses to noxious stimulation in LHb. Cocaine inhibited the delayed
      rectifier K+ current. CONCLUSION: Cocaine can excite the LHb and increase its
      sensitivity. The probable mechanism is that cocaine inhibits the delayed
      rectifier K+ channels.

PMID- 21180129
TI  - [Effect of N(G)-nitro-L-arginine on inflammatory factor and neuronal apoptosis
      after focal cerebral ischemic injury in rats].
AB  - AIM: To evaluate the effect of NG-nitro-L-arginine (L-NA) on inflammatory factor
      and neuronal apoptosis after focal cerebral ischemic injury in rats and the
      possible mechanism of protective effect of L-NA against cerebral ischemic injury.
      METHODS: Thirty male SD rats weighing 250-280 g were randomly divided into three
      groups (n=10): (1) Sham operated group (SH), (2) Ischemic group (IS), (3) L-NA
      group. In L-NA group L-NA 20 mg/kg was given intraperitoneally twice a day for 3
      consecutive days. In IS group normal saline was given instead of L-NA. Focal
      cerebral ischemia was produced by middle cerebral artery occlusion (MCAO) for 12
      h. A nylon thread with rounded tip which was inserted into left internal carotid
      artery cranially until resistance was felt. The distance from bifurcation of
      common carotid artery to the tip of the thread was about 18-19 mm. Focal cerebral
      ischemia was confirmed by left Horner's syndrome and right side hemiplegia. In SH
      group the carotid artery was exposed but no thread was inserted. The expression
      of TNF-alpha was determined by immunochemistry and the content of IL-1beta was
      measured by radio immunity. The Bcl-2 and Bax protein expression were detected by
      flow cytometry. RESULTS: The expression of TNF-alpha and the content of IL-1 beta
      were markedly increased after MCAO. Significantly increased DNA fragmentation
      indication of apoptosis was detected after MCAO. The expression of TNF-alpha and
      the content of IL-1 beta was significantly lower in L-NA group than in IS group.
      The percentage of apoptosis cells and expression of Bax protein were markedly
      lower in L-NA group than in IS group but still significantly higher than in SH
      group. The expression of Bcl-2 protein was markedly higher in L-NA group than in
      IS group. There was no significant difference in the expression of Bcl-2 protein
      between IS and SH group. CONCLUSION: L-NA could inhibit the increase in the
      expression of TNF-alpha and the content of IL-1beta, and protect neurons from
      apoptosis induced by focal cerebral ischemia through increasing the Bcl-2 protein
      expression and inhibiting the Bax protein expression.

PMID- 21180130
TI  - [Study of the neuropsychology and aural event related evoked potential on
      patients with the infarction in basal ganglia region].
AB  - AIM: To learn the condition of the memory and the visual space of the patient who
      has suffered from the infarction in basal ganglia region, and to analyze its
      impact on and the characteristics of the patients' cognition. METHODS: By testing
      respectively on 21 subjects who were initially infarcted in basal ganglia with
      single focus on one side, and 21 healthy volunteers with corresponding age,
      gender and educational background with Rey-Osterrieth Complex Figure Scale (Rey),
      Clinical Memory Scale (CMS), Hospital Anxiety-Depression Scale (HAD), National
      Institute of Health Stroke Scale (NIHSS), Oxford Handicap Scale (OHS), Barthel
      Index (BI), and Aural Event Related Evoked Potential (AERP) as well. RESULTS:
      Compared with the control group, the patient group got higher scores of anxiety
      and depression in HAD), which showed absolutely statistical significance; they
      demonstrated longer reaction time in AERP, which also showed statistical
      significance; and in CMS. they displayed inferior performance in the free picture
      recall and the memory quotient (MQ), which again had statistical significance.
      However, compared with the control group, the patient group got scores with no
      significance in copy, immediate recall and delayed recall in Rey. CONCLUSION: The
      infarction in basal ganglia region with single focus on one side may impact on
      the patient's executive function, memory function and emotion. But no impact is
      showed on patient's visual space function.

PMID- 21180131
TI  - [Effects of HANS' influence on the learning and memory and expression of
      hippocampal SYP of heroin-dependent rats].

PMID- 21180132
TI  - [The affection and significance of NO on the expression of P-selectin in renal
      injury following hind limb ischemia/reperfusion in rats].
AB  - AIM: To probe into the affection and significance of NO on the expression of P
      selectin in renal injury following hind limb ischemia/reperfusion in rats.
      METHODS: In accordance with the conventional approaches of our department, the
      model rats were prepared after they were made to undergo 4 hours or ischemia
      followed by 4 hours of reperfusion of hind limbs. The Wistar rats were divided
      into four groups randomly: Control group, LI/R group, L-Arg group and L-NAME
      group. And then in those four groups of Wistar rats, a series of values of
      measurement were determined such as: Plasma concentrations of nitric oxide (NO),
      blood urea nitrogen (BUN) and creatinine (Cr). Furthermore, biochemically there
      came to the assessment of the values including myeloperoxidase (MPO), NO, total
      nitric oxide synthase (tNOS), inducible NOS (iNOS) and constitutive NOS (cNOS) of
      renal tissue in different groups. By the methods of electrophoresis and
      biochemistry, the urine protein was mensurated. The immunohistochemical method
      was used to detect the expression of P-selectin protein. The morphologic changes
      were observed with a microscope. RESULTS: After hind limbs had suffered from
      ischemia/reperfusion for 4 hours, there was the occurrence of a series of results
      such as in the following which were based on the comparison between plasm of LI/R
      group and control group. The values of NO, BUN and Cr increased significantly,
      and the trend of indexes such as NO in renal tissue was similar to that in
      plasma. The values of MPO, tNOS and iNOS in renal tissue all increased
      significantly after reperfusion, while cNOS decreased distinctly. The urine
      protein appeared, especially large molecular weight protein. Renal pathology
      revealed that after LI/R there were edema and infiltration of polymorphonuclear
      neutrophil (PMN). Immunohistochemically, the expression of P-selectin was
      upregulated significantly. Compared with LI/R rats, all injury changes were
      alleviated in L-Arg group. Morphologic changes were mild. Both the content of
      urine protein and the percentage of apoptosis cell decreased. The expression of P
      selectin was downregulated. In L-NAME group, all injury changes got worse.
      Immunohistochemical results showed strong positive staining of P-selectin.
      CONCLUSION: The renal injury after LI/R may relate to the strong expression of P
      selectin. NO may have protective affection by decreasing the expression of P
      selectin and alleviating the adhesion, aggregation and infiltration of
      neutrophils.

PMID- 21180133
TI  - [Amiloride attenuates hypoxia-induced proliferation of rats pulmonary artery
      smooth muscle cells by suppressing Na+/ H+ exchanger-1].
AB  - AIM: To study the influence of Na+/H+ exchange inhibitor amiloride on hypoxia
      induced proliferation in rats pulmonary artery smooth muscle cells (PASMCs), also
      observe the change of Na+/H+ exchanger-1 (NHE-1) activity and expression.
      METHODS: Rats PASMGs were cultured in normoxia (21% O2) or hypoxia (2%O2) for 24
      hours, as well as administered amiloride with various concentrations, cultured
      for 24 hours, then determined MTT OD values and rates of PCNA positive cells to
      investigate cells proliferation, moreover intracellular pH was determined by
      interactive Laser Cytometer, and Na+/H+ exchanger-1 mRNA expression was
      determined by RT-PCR. RESULTS: Hypoxic exposure heightened intracellular pH and
      mRNA expression of NHE-1 in PASMCs, however, 3.123-50 micromol/L amiloride
      depressed them gradually. Additionally, hypoxic exposure raised MTT OD value and
      rates of PCNA positive cells, similarly, the above two indexes descended
      gradually with presence of 3.125-50 micromol/L amiloride. CONCLUSION: Na+/H+
      exchange inhibitor amiloride can suppress hypoxia-induced proliferation in
      pulmonary artery smooth muscle cells, which is due to depress activity and
      expression of NHE-1.

PMID- 21180134
TI  - [Effects of taurine on the changes of PLA2 during acute lung injury following
      limbs ischemia/reperfusion of rats].

PMID- 21180135
TI  - [Changes of adrenomedullin 2/intermedin in the lung of rats with chronic hypoxic
      pulmonary hypertension].
AB  - AIM: To investigate the changes and probable roles of adrenomedullin2/intermedin
      (AIDM2/IMD), a novel micromolecular bioactive peptide, in the lungs of rats with
      chronic hypoxic pulmonary hypertension. METHODS: Twenty male SD rats were
      randomly divided into normal control group (NC) and normobaric hypoxia group
      (4H). The protein levels of ADM and ADM2/IMD) in the plasma and lung were
      measured by radioimmunoassay and immunohistochemistry. The mRNA expressions of
      ADM, ADM2/IMD and their receptors C (RLR, RAMP1, RAMP2 and RAMP3 in the lung
      tissue were determined by reverse transcription-polymerase chain reaction (RT
      PCR). RESULTS: (1) The rat model of chronic pulmonary hypertension was confirmed
      by the increased mean pulmonary arterial pressure (mPAP) and weight ratio of
      right ventricle to left ventricle plus septum [RV/(LV + S)] in 4H group compared
      to NC group. (2) The concentrations of ADM in the plasma and lung homogenate of
      4H group were 2.3 and 3.2 folds of NC group, respectively (all P < 0.01). The
      levels of ADM2/IMD were higher 89.6% and 45.0% in the plasma and lung homogenate
      of 4H group than those of NC group (respectively, P < 0.01, P < 0.05). (3) The
      mRNA expressions of ADM2/IMD and ADM in the lung of 4H group were up-regulated
      (respectively, P < 0.01, P < 0.05 vs. NC group). The expressions of CRLR and
      RAMP1 mRNAs were down-regulated (all P < 0.01 vs. NC group), while the levels of
      RAMP2 and RAMP3 mRNAs were no significant difference between the two groups. (4)
      The strong ADM2/IMD immunostaining was detected in the endothelial and
      adventitial cells of the rat pulmonary arteriole. CONCLUSION: ADM2/IMD, like its
      paralog ADM, might be closely related to the chronic hypoxic pulmonary
      hypertension in rats. The disorders of the gene expression and/or the synthesis
      and metabolism of ADM2/IMD and its receptor CRLR/RAMP1 possibly take part in the
      pathogenesis of chronic hypoxic pulmonary hypertension in rats.

PMID- 21180136
TI  - [Effect of Fructus Gardeniae-zhizi on isolated gastric muscle strips in rabbits].

PMID- 21180137
TI  - [Study on relativity of hypoxic pulmonary hypertension with levels of endothelin
      1 and vascular endothelial growth factor in plasma of pulmonary artery and
      carotid artery].
AB  - AIM: To study the effects of endothelin-1 (ET-1) and vascular endothelial growth
      factor (VEGF) on the mechanism of hypoxic pulmonary hypertension (HPH). METHODS:
      We studied 4 groups of age-controlled male rats, i.e., normal control for 2 weeks
      group (N2), normal control for 3 weeks group (N3), exposed to hypoxia for 2 weeks
      group (H2) and for 3 weeks group (H3). Chronic HPH rat models were established by
      chronic hypobaric hypoxia [(10.0% +/- 0.5% O2] for 2 and 3 weeks, respectively.
      The rats were anesthetized and fixed, and the levels of mean pulmonary artery
      pressure (mPAP) and carotid arterial pressure (CAP) were measured using catheters
      by a microcomputer via transducers. The weight ratio of right ventricle (RV) and
      left ventricle and septum (LV + S) [RV/ (LV+S)] were determined. The contents of
      ET-1 in plasma of pulmonary artery and carotid artery and in homogenates of lung
      and systemic arteries were determined by radioimmunoassay, and the contents of
      VEGF in serum of pulmonary artery and carotid artery were determined by ABC
      ELISA. RESULTS: HPH rat models were established successfully. Compared with
      control groups, the values of ET-1 were both enhanced in carotid artery and
      pulmonary artery plasma in model groups (P < 0.01). In the HPH groups, the level
      of pulmonary artery plasma ET-1 was significantly lower than that of carotid
      artery plasma, but just the reverse was ET-1 in control rats. The levels of ET-1
      in homogenates of lungs from HPH models were significantly higher than those in
      homogenates of lungs from control groups (P < 0.01), and markedly higher than
      those in homogenates of systemic arteries from HPH rats (P < 0.01) SThe values of
      VEGF in serum of pulmonary artery from H3 group were significantly higher than
      those from control groups and H2 group (P < 0.01). In serum of carotid artery,
      the values of VEGF from the HPH models were higher than those from the control
      groups (P < 0.01). CONCLUSION: ET-1 and VEGF play important roles in the
      pathogenesis of HPH. The result that ET-1 concentration around pulmonary arteries
      was significantly higher than that around systemic arteries may be one of the
      mechanisms accounting for the different reaction of them to hypoxia.

PMID- 21180138
TI  - [Effects of splenic B lymphocyte proliferation and response and intracellular
      Ca2+ of hsBAFF in mice].
AB  - AIM: To investigate effects of hsBAFF synthesized in Escherichia coli on spleen B
      lymphocyte immune response and its intracellular free Ca2+ ([Ca2]i]) signaling in
      mice. METHODS: Twenty ICR mice, half males-half females, were chosen and randomly
      divided into a normal control group (n=10) and a hsBAFF treatment group (n-10).
      The mice in hsBAFF treatment group were given abdominal cavity injection of
      hsBAFF solution which was diluted with phosphate buffered saline (PBS) at dosage
      of 0.1 mg/kg body weight once each day for over eight days. The mice in control
      group were received abdominal injection of PBS at the same dose and frequency.
      Spleen B lymphocyte proliferation and its immune response to LPS stimulation in
      mice were evaluated using an MTT assay, and change of spleen B lymphocyte [Ca2+]i
      was assayed under a laser scanning confocal microscope. RESULTS: B lymphocyte
      proliferation and its immune response to LPS stimulation were significantly
      higher in hsBAFF-treated mice than in control mice (P < 0.05). The B lymphocyte
      [Ca2+]i fluorescence intensity in hsBAFF-treated mice maintained at a relatively
      high level fluctuation, and its average intensity was significantly higher to
      that of control mice (P < 0.01), but change rate of the intensity was lower
      compared to that of control group. CONCLUSION: hsBAFF synthesized in Escherichia
      coli can enhance immune function in the body by increasing B lymphocyte
      proliferation and its immune response. hsBAFF-activated B lymphocyte function may
      be associated with increasing B lymphocytes [Ca2+]i.

PMID- 21180139
TI  - [Effect of Salvia miltiorrhiza monomer IH764-3 on MMP-13 and TIMP-1 by
      downregulating the expression of focal adhesion kinase in hepatic stellate cell
      stimulated by H2O2].
AB  - AIM: To investigate the effect of IH764-3 on the expression of MMP-13 and TIMP-1
      by H2O2-stimulated hepatic stellate cell and the alteration of FAK during this
      process. METHODS: The expression of MMP-13 and FAK mRNA was examined by RT-PCR.
      TIMP-1 mRNA was analyzed by in-situ hybridization. FAK and TIMP-1 were evaluated
      at protein level through Western blotting method. RESULTS: Being incubated for 2
      h, compared with control group, MMP-13 mRNA was upregulated by IH764-3, but TIMP
      1 transcription was reduced in a dose-dependent manner, accompanied with the
      decrease of FAK mRNA. The expression of TIMP-1 and FAK protein in HSC also
      decreased after being exposed by IH764-3 for 24 h. CONCLUSION: IH764-3 can induce
      the expression of MMP-13 and inhibit the expression of TIMP-1. Down-regulating
      the expression of FAK mRNA may be one of its mechanisms.

PMID- 21180140
TI  - [Effect of glucose-6-phosphate dehydrogenase on intracellular gsh level in Raji
      cells during oxidative stress].
AB  - AIM: To explore a role of G6PD in replenishment of intracellular GSH during
      oxidative stress. METHODS: In vitro Raji cell was cultured, intracellular GSH
      levels and G6PD, GR, GPX activities were determined at different time points
      after PMS treatment when G6PD activity was inhibited or not by DHEA. RESULTS:
      Intracellular GR, GPX, G6PD activities elevated significantly combined with GSH
      level decreased dramatically before 30 minutes, replenished gradually after 30
      minutes and restore normal levels about 6 h after PMS treatment when G6PD was not
      inhibited. No change in GR and significant increase in GPX activity were shown
      following depleted GSH after PMS treatment when G6PD was inhibited by DHEA.
      CONCLUSION: G6PD contributes to replenish intracellular GSH and is a critical
      factor regulating GSH levels during oxidative stress.

PMID- 21180141
TI  - [Effects of coenzyme Q10 supplementation on liver mitochondrial function and
      aerobic capacity in adolescent athletes].
AB  - AIM: To investigate the effects of CoQlo supplementation on liver mitochondrial
      function and aerobic capacity in adolescent athletes. METHODS: Based on a single
      blinded study design, 18 male adolescent swimming athletes were randomized into
      two groups, supplement CoQ10 100 mg/d (Q group), or placebo (P group) for 28 days
      respectively. RESULTS: (1) After supplementation, the plasma CoQ10 concentration
      in Q group was significantly elevated and significantly higher compared to P
      group. (2) After supplementation, the rest plasma MDA level in Q group remained
      unchanged and was significantly lower compared to P group. (3) The plasma CoQ10
      concentration of the 18 athletes was significantly decreased during the first
      constant endurance exercise. (4) The baseline plasma CoQ10 of the 18 subjects
      showed significantly positive correlation with VO2max measured in the first
      incremental exercise. (5) No significant difference of increased level of AKBR
      between Q group and P group. (6) No significant difference of increase level of
      VO2max, individual lactate threshold and exercise economy between Q and P group.
      CONCLUSION: Although there is an increased demand for plasma CoQ10 during
      endurance exercise and CoQ10 supplement can depress lipid peroxidation, there is
      no effect of CoQ10 supplementation on liver mitochondrial function and aerobic
      capacity in adolescent athletes.

PMID- 21180142
TI  - [Experimental study on inhibition of restenosis by osteopontin oligopeptide
      antagonist after de-endothelium].
AB  - AIM: Osteopontin 13-peptide(Gly158-Lys170), containing multi-function domains was
      used to inhibit the VSMC adhesion, migration. The mechanism of 13-peptide
      inhibiting neointima formation was investigated. METHODS: The effect of 13
      peptide on VSMC adhesion was tested by adhesion assay. The restenosis model was
      prepared balloon injury after administration of 13-peptide for 1 h, and then the
      13-peptide was given by an intravenous drip for 7 days. The expression changes of
      OPN, FAK, ILK in vessel wall were detected by immunohistochemistry and Western
      blot. RESULTS: The 13-peptide dose-dependently reduced adhesion of VSMC in OPN
      matrix, and the infiltration of macrophage in vessel wall also was reduced in the
      treatment group after balloon injury. The expression of OPN, FAK, ILK was down
      regulated following with the inhibition of neointima thickening. CONCLUSION: The
      OPN 13-peptide can inhibit inflammation and neointima formation by blocking the
      binding of OPN to it's receptors.

PMID- 21180143
TI  - [Effects of morphine on the development of chick embryos].
AB  - AIM: To investigate the effect of morphine on fetal movement, heart rate, hatch
      weight, hatch days and hatch rate. METHODS: Morphine was injected into airspace
      of eggs and fetal movement, heart rate, hatch weight, hatch days and hatch rates
      were recorded. RESULTS: Hatch days were shorter, hatch rates were lower and some
      chicks became motor disorder for morphine. Chicks with morphine exposure 20 mg/kg
      from E 12 to E 16 had highest hatch rate and lowest disable rate. Morphine
      reduced fetal movement, increased heart rate (P < 0.05). CONCLUSION: The
      development of chick embryo is impaired by morphine exposure and the magnitude of
      these effects depends on the drug dose and the length of time that the developing
      organism is exposed to morphine.

PMID- 21180144
TI  - [Comparison between anti-ouabain egg yolk(IgY) and rabbit antibody(IgG) in enzyme
      linked immunosorbent assay].
AB  - AIM: To improve specificity and accuracy of endogenous ouabain measurement assay.
      METHODS: Anti-ouabain polyclonal antibody egg yolk (IgY) and anti-ouabain rabbit
      antibody (IgG) were prepared respectively. In the presence of two kinds of
      antibody, then the specificity and accuracy of enzyme-linked immunosorbent assay
      (ELISA) were compared. RESULTS: The ELISA, in the presence of IgY, provided a
      sensitivity of the average intraassay coefficient of variation(CV) was 2.03%, and
      the inter-assay CV was 2.34% respectively. In contrast, IgG were 2.83% and 3.29%.
      No significant interferences were observed with hydrocortisone and dexamethasone.
      There was 3.45% vs. 5.95%, 3.20% vs. 5.20% of crossreaction with cedilanid and
      digoxin. CONCLUSION: The specificity and accuracy of ELISA, in which IgY was
      used, were more better than IgG.

PMID- 21180145
TI  - [Establishment of the coculture systems of rabbit aortic endothelial cells and
      smooth muscle cells].
AB  - AIM: In order to establish a coculture system of ECs and SMCs and by which
      further study can be done. METHODS: ECs in primary culture were grown on a side
      of Transwell membrane, and SMCs were grown on an other side of it or the bottom
      of culture well, so that two kinds of coculture systems were established, and
      detail observation on the coculture systems was carried out by transmission and
      scanning electron microscope. RESULTS: ECs in primary culture were positive of VI
      factor by immunocytochemistry staining. ECs and SMCs were grown well on both
      sides of Transwell membrane, relative to ECs monolayer of "cobblestone
      appearance", SMCs were multilayer of "hills and valleys appearance". ECs and SMCs
      on both sides of Transwell membrane could form the gap junctions by micropores.
      CONCLUSION: The coculture systems of ECs and SMCs were established successfully
      by modeling the structural relationship of vascular wall.

PMID- 21180146
TI  - [The regulation of area postrema in cardiovascular function in rabbit].
AB  - AIM: To determine the role of area postrema (AP) of rabbit in the regulation of
      cardiovascular function. METHODS: The rabbits were anesthetized with intravenous
      injection of 10% urethane and 1% chloralose, and were artificially ventilated.
      The changes of mean arterial pressure (MAP) and heart rate (HR) were observed
      when AP was electrically stimulated with different frequency (10 Hz -80 Hz) and
      after chemical lesion of CVLM or RVLM, respectively. RESULTS: Electrical
      stimulation of AP with low frequency (10 Hz, 20 Hz) decreased MAP and HR.
      Stimulation with high frequency(60 Hz, 80 Hz) increased MAP but decreased HR. The
      changes in MAP and HR were significantly lower (P < 0.01) after CVLM was
      destroyed when electrical stimulation of AP with 20 Hz, and both changes of MAP
      and HR were disappeared (P < 0.01) after RVLM was destroyed when electrical
      stimulation with 20 and 80 Hz. CONCLUSION: Electrical stimulation of AP with low
      frequency decreases MAP and HR, stimulation with high frequency induces an
      increase in MAP and decreases in HR. The former is probably related to excitation
      of CVLM, the cardiovascular effects induced by different frequency of electrical
      stimulation are all resulted from the activation of RVLM.

PMID- 21180147
TI  - [Effects of leptin on RNA content of LHA, VMH, PVN and the body fat].

PMID- 21180148
TI  - [Adaptation of myofibrilla, MHC and metabolic enzyme of rabbit diaphragm muscle
      to different frequency chronic electrical stimulation].
AB  - AIM: To detect effect of the different frequency of chronic electrical
      stimulation (CES) on myofibrillar isoform, myosin heavy chain (MHC) and metabolic
      enzyme activities. METHODS: The histochemical method and SDS-polyacrylamide gel
      electrophoresis were respectively employed. RESULTS: (1)There were a significant
      increase in I myo-fibrillar isoform and I MHC isoform and decrease in II B
      myofibrillar isoform and II B MHC isoforms in the chronic low frequency
      electrical stimulation (CLFES) 10 Hz and 20 Hz groups, but opposite results were
      found in the chronic high frequency electrical stimulation (CHFES) 50 Hz and 100
      Hz groups. (2) There were a significant increase in the aerobic-oxidative enzyme
      activities and capacity, and a concomitant significant drop in glycolysis enzyme
      activities in CLFES groups, but opposite results were found in CHFES 50 Hz and
      100 Hz groups. CONCLUSION: It was suggested that there was a significant
      dependent relation between chronic electrical stimulation frequency and
      myofibrilla isoforms, myosin heavy chain (MHC) and metabolic enzyme activities.

PMID- 21180149
TI  - [Enhanced reporter gene transfer and expression in cardiac myocytes mediated by
      ultrasonic destruction of the microbubbles].
AB  - AIM: To determine if the diagnostic ultrasound and self-made microbubbles could
      be used to increase gene transfection and expression in cardiac myocytes by means
      of the ultrasound-mediated microbubbles destruction. METHODS: The
      perfluoropropane-exposed sonicated dextrose albumin(PESDA) microbubbles were made
      and mixed with indicated volume reporter gene encoding beta-galactosidase prior
      to gene transfection. Gene transfection into the cultured cardiac myocytes was
      performed by exposure to the various intense diagnostic ultrasound (1.3 MHz) in
      the presence of the gene-attached microbubbles. The calcium phosphate
      precipitation gene transfection was carried out alone or in combination with
      ultrasound-mediated destruction microbubbles. The cells were harvested 48 h after
      transfection and beta-galactosidase expression was detected by in situ staining
      and quantitive assay. RESULTS: Cardiac myocytes exposed to ultrasound with PESDA
      induced significantly increase in gene expression (60-fold compared with naked
      plasmids transfection, P < 0.01). Moreover, it was found that the reporter gene
      expression not only related with ultrasound intension but also with the
      microbubbles concentration. In combination with calcium phosphate precipitation
      gene transfection, ultrasound-mediated destruction microbubbles resulted in more
      intense gene expression even 6 hours after calcium phosphate precipitation gene
      transfection. CONCLUSION: The ultrasonic destruction of gene-loaded microbubble
      is a highly effective gene transfer method, and it not only acts on the gene
      entry into cells, but also on the intracellular exogenous DNA expression.

PMID- 21180150
TI  - [Effects of conotoxin SO3 on free calcium ion concentration in rat cultured
      hippocampal neurons induced by hypoxia].

PMID- 21180151
TI  - [Dynamic changes of urotensin II receptor in pulmonary artery and arterioles of
      rats chronically exposed to hypoxia-hypercapnia].
AB  - AIM: To investigate the dynamic changes and functions of urotensin II (U lI)
      receptor (UT) in pulmonary arteries of rats chronically exposed to hypoxia
      hypercapnia. METHODS: In rats with hypoxia-hypercapnia at 1, 2 and 4 weeks U II
      receptor binding of pulmonary arteries sarcolemma was determined by radioligand
      assay. U II mRNA and UTmRNA in various grades of pulmonary arterioles were
      measured by in situ hybridization. RESULTS: (1) Mean pulmonary pressure (mPAP)
      and weight ratio of right ventricle to left ventricle and septum (RV/LV + S) of 1
      week group were higher than those of normal control (NC) group by 26.2% and 21.6%
      (P < 0.01), respectively, and 2-week group higher than 1-week group by 22.5% and
      14.1% (respectively, P < 0.01). However, no significant changes were found
      between 4-week and 2-week group. (2) U Il receptor (Bmax) of 1-week group was
      higher than NC group by 38.8%, 2-week group higher than 1-week group by 23.2%,
      and 4-week group increased 7.3% compared with 2-week group (respectively, P <
      0.01). The UT changes were time-dependent, while the affinity to U II (Kd) was no
      different among each group. (3) UII mRNA in each grade of pulmonary arterioles of
      2-week group and 4-week group were higher than NC group (respectively, P < 0.01),
      and those of 2-week group were higher than 1-week group by 5.9% (P > 0.05), 16.4%
      and 9.1% (respectively, P < 0.01), while no differences existed between 2-week
      group and 4-week group. (4) UT mRNA in each grade of pulmonary arterioles of all
      hypoxia-hypercapnia groups was higher than NC group (respectively, P < 0.01), and
      those of two abaxial grade vessels in 1-week group were the highest. No
      differences existed between 2-week group and 4-week group. (5) The pulmonary
      vessels remodeling were time-dependently aggravated by hypoxia-hypercapnia.
      CONCLUSION: The dynamic changes of UT in pulmonary arterioles might have
      important contribution to the development of pulmonary hypertension and pulmonary
      arteriole remodeling induced by chronic hypoxia-hypercapnia in rats.

PMID- 21180152
TI  - [Excitatory characteristics of glutamate on hippocampus neurons cultured in
      vitro].

PMID- 21180153
TI  - [Effects of proanthocyanidins on contractile activity of aortic smooth muscle and
      platelet aggregation in experimental animals].
AB  - AIM: To study effects of proanthocyanidins (PA) on contractile activity of
      isolated aortic smooth muscle in rats and rabbit platelet aggregation. METHODS:
      Isolated rat aortic muscle rings were adopted to observe the effects of PA on
      their contraction induced by noradrenaline (NA) or KCl, and their tensions were
      recorded by BL-310 experimental system of biological function. Rabbit platelet
      aggregation induced by arachidonic acid (AA), adenosine diphosphate (ADP), and
      collagen (Coll) was assayed by turbidimetry. RESULTS: PA could significantly
      inhibit the contraction induced by NA (10(-6) mol/L), low the concentration
      response curves of NA and the maximal response on the endothelium-intact or
      endothelium-denuded aortic rings. But PA couldn't relax the aortic rings
      precontracted with KCl and had no influence on rabbit platelet aggregation
      induced by AA, ADP, and Coll. CONCLUSION: PA can inhibit the contraction induced
      by NA but not by KCl on isolated rat aortic rings. It also has no influence on
      rabbit platelet aggregation.

PMID- 21180154
TI  - [Role of heme oxygenase-1 in the ischemic preconditioning of isolated rat heart].

PMID- 21180155
TI  - [Role of MAPK in the migration of human coronary artery smooth muscle cell into
      three-dimensional fibrin gel].
AB  - AIM: To investigate the role of MAPK in the migration of human coronary artery
      smooth muscle cells(HCASMC ) into three-dimensional fibrin gels. METHODS: HCASMC
      were primarily cultured. HCASMC migration was measured with a phase-contrast
      microscope in the presence or absence of PD98059, SB203580, and SP600125, the
      inhibitors of ERK, p38, and JNK, respectively. Phosphorylation of ERK, p38 and
      JNK were analyzed by Western blotting in the presence or absence of PD98059,
      SB203580 or SP600125. RESULTS: HCASMC that migrated into the three-dimensional
      fibrin gel exhibited a characteristic elongated spindle-shaped appearance and
      formed vessel-like structure. The number of migrated HCASMC increased with
      incubation time and concentration of fibrinogen in the range between 0.8 g/L and
      6.4 g/L. Western blot showed that fibrin induced phosphorylation of ERK, p38 and
      JNK time dependently and PD98059, SB203580 and SP600125 could inhibit their
      activation, respectively. Migration of HCASMC into the fibrin gels was inhibited
      by SP600125 20 micromol/L and SB203580 10 micromol/L, respectively. Furthermore,
      inhibition of SP600125 20 micromol/L had a more profound effect. PD98059 50
      ,mol/L, however, failed to influence migration of HCASMC. Hence, migration of
      HCASMC into the fibrin gels is JNK- and p38-dependent, but not ERK-dependent.
      CONCLUSION: Fibrin gel induces HCASMC migration into itself by activation of JNK
      and p38, but not ERK, which may play an important role in pathogenesis of
      atherothrombosis and restenosis.

PMID- 21180156
TI  - [Role of TNF-alpha in vascular endothelial cells injury mediated by frozen/thawed
      PMN].
AB  - AIM: To investigate the role of TNF-alpha in vascular endothelial cells injury
      mediated by freezing/thaw ing PMN. METHODS: Freezing/thawing cell model was
      founded using rat PMN isolated by dextran sedimentation technique and VEC
      cultured in vitro. The injury level of VEC was indicated by measuring activity of
      LDH in medium. The number of frozen/thawed PMN adhering to VEC was counted with
      Phagocytizing reactive dyes the degree of frozen/thawed PMN and VEC adhesion.
      Expression of LFA-1 on the surface of frozen/thawed PMN was analyzed with flow
      cytometry. RESULTS: TNF-alpha could obviously upregulate expression of LFA-1 on
      surfaced of frozen/thawed PMN. Upregulation of LFA-1 expression promoted adhesion
      of frozen/thawed PMN and normal VEC,and aggravated VEC injury. Monoclonal
      antibody against LFA-1 could partly block adhesion of frozen/thawed PMN and
      normal VEC,and attenuate VEC injury. CONCLUSION: TNF-alpha can promote expression
      of LFA-1 on surface of frozen/thawed PMN adhering of frozen/thawed PMN to normal
      VEC and VEC injury increase, monoclonal antibody against LFA-1 could partly block
      PMN-VEC adhesion and attenuate VEC injury.

PMID- 21180157
TI  - [Protecting effect of human-derived neurotrophin-6 on retrogradely degenerated
      motoneurons of facial nucleus of rats].
AB  - AIM: The protecting effect of human-derived neurotrophin-6 (NT-6) on injured
      neurons was investigated to test the neurobiological characteristics of human
      derived NT-6. METHODS: Adult SD rats were used and divided into two groups,
      normal control group and experiment group. The right facial nerve of the
      experimental rats was sectioned. The experimental animals were subdivided into
      three groups, blank control group, NT-6 group and saline control group. The rats
      were raised for two weeks. Brain stem of the rats was removed and transversely
      sliced. Nissle stain and ChAT immunohistochemical stain of the slices were
      carried out to observe the role of NT-6 in protecting facial motoneurons.
      RESULTS: The number of the ChAT positive neurons and the intensity of Nissle
      stain in the facial nucleus of NT-6 group were significantly augmented compared
      with that of the blank and saline control groups. CONCLUSION: The human-derived
      NT-6 could partially protect the facial motoneurons from retrograde degeneration
      induced by their axon damage.

PMID- 21180158
TI  - [Treatment of hypoxic ischemic encephalopathy of newly born rats by acupuncture].

PMID- 21180159
TI  - [Effects of Chinese herbs on glucocorticoid receptor in rat brain regions with
      chronic immobilization stress].
AB  - AIM: To investigate the changes of glucocorticoid receptor (GR) in rat brain
      regions with chronic immobilization stress and the influence of Chinese herbs.
      METHODS: We copied the rat model of chronic immobilization stress (180 min daily,
      repeated 7 days or 21 days), and characterized the changes of GR in hippocampus
      CA1, cortex, dentate gyrus via immunohistochemistry integrated image analysis.
      RESULTS: The contents of glucocorticoid receptors in hippocampus CA1 , cortex,
      dentate gyrus were increased and the intensity of immunity reaction was
      significantly stronger in the model group of 7 days than that in the normal
      control group (P < 0.05). The contents of GR were significantly decreased and the
      intensity of immunity reaction was weaken in the model group of 21 days (P <
      0.05). CONCLUSION: Compared with the model group of 21 days, the contents of GR
      were significantly increased and immunity reaction was intensified in three
      groups of treatment with Chinese herbs (P < 0.05), in which the group treated
      with soothing-liver herbs Xiaoyaopowder was the best.

PMID- 21180160
TI  - [Regulatory network of hippocampal-systemic arterial blood pressure during
      epileptic network reestablishment].
AB  - AIM: To investigate the regulatory network of hippocampal-systemic arterial blood
      pressure during epileptic network reestablishment. METHODS: 7.2 microg picrotoxin
      (PTX) was microinjected into the right HPC (RHPC) to induce rat epilepsy.
      Contralateral hippocampal EEG, single unit discharges, femoral artery blood
      pressure and ECG were recorded simultaneously. RESULTS: PTX might induce: (1) A
      resemblance interspike intervals (ISI) spot distribution of long duration
      neuronal burst and unit after discharges in contralateral HPC. (2) Delayed the
      initiation time of hippocampal neuronal bursts coupled with arterial blood
      pressure depression. (3) Hippocampal neuronal burst or unit after discharges
      coupled complexly with arterial blood pressure depression. (4) Resemblance
      hippocampal EEG interpeak intervals (IPI) and neuronal firing ISI spot
      distribution coupled with arterial blood pressure depression. CONCLUSION: During
      contralateral hippocampal epileptic network reestablishment after microinjection
      of PTX to the RHPC, the function of the hippocampal-arterial blood pressure
      regulatory network could be modulated by characteristic network and neuronal
      temporal code patterning.

PMID- 21180161
TI  - [The effect of chronic intermittent hypoxia to hypothalamus-pituitary-adrenal
      axis and growth hormone level in rats during sleep].
AB  - AIM: To research the effect of intermittent hypoxia during sleep on hypothalamus
      pituitary-adrenal (HPA) axis and growth hormone (GH) level. METHODS: Rats were
      respectively exposed to intermittent hypoxia, room air and continuous hypoxia,
      after 1 day, 3 days, 7 days and 30 days, mRNA levels of corticotropin-releasing
      hormone (CRH) and growth hormone releasing hormone (GHRH) in hypothalamus of rats
      were detected using RT-PCR, and the levels of CRH, GHRH, corticotropin(ACTH),
      cortex ketone, and growth hormone in plasma were measured. RESULTS: After 30
      days, the CRH mRNA levels in rats hypothalamus which exposed to intermittent
      hypoxia were increased significantly than those exposed to continuous hypoxia as
      well as normal control but GHRH decreased, there was no difference between
      continuous hypoxia and normal control. After 1 day, 3 days, and 7 days, there was
      no difference between continuous hypoxia and intermittent hypoxia. After 30 days,
      the plasmic level of CRH,ACTH and cortex ketone increased, GHRH decreased and GH
      had no obvious change. CONCLUSION: The rats' HPA axis level increases and GHRH
      restrained with chronic intermittent hypoxia during sleep, feedback regulation
      disorders.

PMID- 21180162
TI  - [Research of relationship between lower body strain and G-tolerance].

PMID- 21180163
TI  - [The response of hypothalamic CRF and AVP neurons of neonatal rats to simulated
      acute hypoxia].
AB  - AIM: To investigate the response of hypothalamic corticotropin releasing factor
      (CRF) and arginine vasopressin (AVP) of adrenalectomized neonatal rats to
      hypoxia. METHODS: The hypoxia was simulated in hypobaric cabin. The amount of
      arginine vasopressin (AVP) and corticotropin releasing factor (CRF) was assayed
      by RIA method. RESULTS: When neonatal rats exposed to acute hypoxia (simulated
      altitude of 5 000 m and 7 000 m, 24 h), their hypothalamic CRF was not changed in
      3 d and 7 d rats, lower than control in 14 d, 21 d and 28 d rats, while
      hypothalamic AVP had no change in 3 d rats, was lower than control in 14 d and
      higher in 7 d, 21 d and 28 d rats. The responsive pattern of those two
      neuropeptides to acute hypoxia changed with the growth of rats. Adrenalectomy
      reduced the amount of hypothalamic CRF and AVP in 14 d, 21 d and 28 d rats,
      except AVP in 28 d rats. When adrenalectomized neonates exposed to hypoxia, there
      was no further change in CRF and AVE, means adrenalectomy not only removed the
      negative regulation of corticosteroid on CRF and AVE, but also inhibited the
      normal development of CRF and AVP neurons and thus, their responsive ability to
      hypoxia.

PMID- 21180164
TI  - [Changes in expression of apoptosis correlative proteins and HIF-1 during acute
      hypoxia and hypoxic preconditioning in cultured cardiomyocyte of rat].
AB  - AIM: To investigate the relationship between the hypoxia-inducible factor 1(HIF
      1) and apoptosis correlative proteins in the cardiomyocyte during hypoxia.
      METHODS: Rat cardiomyocytes cultured in vitro were divided into normoxia, hypoxia
      and hypoxic preconditioning groups. The cardiomyocytes in hypoxic preconditioning
      group were cultured in 1% O2, 5% CO2, 94% N2 for 5 days, 12 h daily before
      exposed to 0% O2 hypoxia with the hypoxic group. The protein expression of HIF
      1alpha, Bcl-2, P53 and Bax in the cardiomyocytes were analysis with Western blot
      after 48 h 0% O2 hypoxia. RESULTS: With the increment of HIF-1 expression, the
      Bcl-2 expression was inhibited, the Bax and P53 expression were increased as well
      during hypoxia. Hypoxic preconditioning could suppress the HIF-1 expression,
      meanwhile the Bcl-2 expression was elevated, and the Bax expression was
      decreased. CONCLUSION: HIF-1 may contribute to the regulation of the
      cardiomyocyte apoptosis with the Bcl-2 family during hypoxia.

PMID- 21180165
TI  - [Effect of ligustrazine on the expression and activity of heme oxygenase-1 in the
      pulmonary ischemia/reperfusion injury in rabbits].
AB  - AIM: To explore the effect of ligustrazine injection on the expression of heme
      oxygenase-1 (HO-1) in rabbits with pulmonary ischemia/reperfusion injury after.
      METHODS: Single lung ischemia/reperfusion injury animal model was used in vivo.
      Twenty rabbits were randomly divided into two groups( n = 10, in each), pulmonary
      ischemia/reperfusion injury (I/R) group and I/R + ligustrazine injection (LGT)
      group. The tissue slides were stained by immunohistochemistry (IHC) and in situ
      hybridization (ISH) for HO-1 to detect the expression of HO-1 in lung and to
      analyze the absorbance, wet to dry ratio of lung tissue weight (W/D) and the
      injured alveoli rate (IAR) were measured at 180 minutes after lung reperfusion.
      Meanwhile the lung tissue slide was prepared for electron microscopic observation
      at 180 minutes after reperfusion. RESULTS: HO-1 expression was upregulated in two
      groups in the pulmonary endothelial cells, part of pulmonary vascular smooth
      muscle cells, extima of vessels and epithelial cells of airway, the absorbance
      was 0.168 +/- 0.016 (0.148 +/- 0.013), 0.186 +/- 0.014 (0.158 +/- 0.012)
      respectively.The LGTI group showed higher absorbance than those of the I/R group
      (P < 0.01), lower W/D and IAR values than those of the I/R group (P < 0.01)
      significantly and lighter abnormal changes of the lung tissue in morphology than
      those of the I/R group. CONCLUSION: Ligustrazine injection possesses notable
      protective effects on I/R in rabbits by increasing the expression of HO-1 in
      lung.

PMID- 21180166
TI  - [Electrophysiological effects of estradiol with progesterone on action potential
      and contraction of guinea pig papillary muscle].

PMID- 21180167
TI  - [Study on the changes of the leptin receptor expression and neuronal damage
      following focal ischemia/reperfusion in rats].
AB  - AIM: To study the expression of leptin receptor (OB-R) and neuronal damage
      following focal ischemia/reperfusion in rats. METHODS: 20 adult male Wistar rats
      were divided into four groups randomly: sham-operated 24 h,72 h control group and
      ischemic/reperfusion 24 h, 72 h experiment group. Focal ischemia/reperfusion
      model was made with MCAO. Immunohistochemistry and immunoelectron microscope were
      used to observe the expression of OB-R of the cortex and neuronal damage.
      RESULTS: The positive cells of OB-R were found in pyramidal cells of the parietal
      cortex, choroid plexus and blood vessel endothelium. Compared with sham-operated
      group, significant reduction of OB-R positive cells in the pyramidal cells was
      observed in the ischemia/reperfusion rats 24 hours after cerebral ischemia (P <
      0.05). The positive cells of OB-R of sham-operated 72 h group reduced further (P
      < 0.01). Histochemistry and electron microscope showed neuronal damage in the
      core area of cerebral ischemia in the late period was more obvious than in the
      early period. CONCLUSION: The early and delayed ischemia/reperfusion neuronal
      damage were accompanied with reduction of OB-R expression. Thus, it is worth to
      study the effect of OB-R in cerebral ischemia.

PMID- 21180168
TI  - [Effects of PKC activation on apoptosis during ischemia/reperfusion in L-6TG rat
      skeletal myoblasts].
AB  - AIM: To study the effects of PKC activation on apoptosis during
      ischemia/reperfusion in L-6TG rat skeletal myoblasts. METHODS: Cultured L-6TG
      cells were divided into 3 groups: control group (C), ischemia/reperfusion group
      (I/R), PMA + ischemia/ reperfusion group (PMA), SOD, XOD and free calcium and
      mitochondrial respiration in L-6TG cell were evaluated in each group. Apoptosis
      was detected by flow cytometer with PI staining method and agarose gel
      electrophoresis, the immunohistochemical method was used to determine the
      expression of caspase-3. RESULTS: Compared with I/R group, in PMA group, XOD ,
      free calcium in L-6TG cell and apoptotic percentage all decreased significantly,
      while SOD and mitochondrial respiration in L-6TG cell increased. DNA
      fragmentation analysis of L-6TG cell showed no laddering pattern. The expression
      of caspase-3 was down regulated significantly. CONCLUSION: Activation of PKC can
      lessen ischemia/reperfusion injury and apoptosis through lessening oxidative
      injury and mitochondrial injury, adjusting calcium dyshomeostasis and down
      expression of caspase-3.

PMID- 21180169
TI  - [Adenosine release in human endothelial cells].

PMID- 21180170
TI  - [Antagonistic effect of metallothionein against homocysteine-induced vascular
      endothelial cell's lipid hyper oxidative injury].

PMID- 21180171
TI  - [Establishment of heterologous expression model of hSERT in Xenopus laevis
      oocytes].
AB  - AIM: To determine the feasibility of establishing the heterologous expression
      model of human- serotonin transporter(hSERT or 5-HTT). METHODS: cRNA of SERT was
      transcribed from cDNA, which was cloned in the pOTV vector. Each oocyte of mature
      xenopus laevis was injected with transcribed cRNA in vivo and incubated at room
      temperature for 4-9 days. Recording the current induced by 5-HT with voltage
      clamp technique tested the function of the expressed 5-HT transporter. RESULTS:
      The transporter current could be observed in Ringer's solution containing 5-HT,
      and the 5-HT induced current were concentration-dependent. Norepinephrine and
      dopamine could not induce the transporter current while the 5-HT induced current
      could be specifically inhibited by 5-HTT blocker, desipramine. CONCLUSION: The
      results demonstrate that the heterologous expression product in xenopus laevis
      oocytes is human 5-HT transporter.

PMID- 21180172
TI  - [Non-specific effect of myosin inhibitor BDM on skeletal muscle contractile
      function].
AB  - AIM: In order to elucidate the underlying mechanism of depressed maximal
      isometric twitch tension normalized by cross sectional area of muscle strip in
      unloaded soleus. METHODS: The soleus and extensor digitorum longus (EDL) muscle
      strips were perfused in vitro and treated by 2,3-Butanedione monoxime (BDM).
      RESULTS: The BDM decreased Pt of soleus and EDL in a concentration-dependent
      manner. The Pt could restored completely to normal level after washing out BDM.
      The isometric twitch duration was not altered during 1 mmol/L BDM of perfusion,
      but was shortened at 10 mmol/L dose. The time from maximal to half Pt in EDL was
      shorter than that in soleus during 10 mmol/L BDM of perfusion. The inhibitory
      effects of BDM on myosin ATPase activity were higher in EDL than in soleus. The
      inhibitory extent of BDM on myosin ATPase activity of soleus and EDL was lower
      than that on Pt. CONCLUSION: These results suggest that reduction in cross-bridge
      function of skeletal muscle may be one of reasons induced a decrease in its Pt.
      BDM is not a specific inhibitor on myosin ATPase activity and can affect multiple
      parts of excitation-contraction coupling in skeletal muscle.

PMID- 21180173
TI  - [Study of the gene deletions and the immunofluorescence of muscle in patients
      with DMD/BMD].
AB  - AIM: To detect the deletion distribution of dystrophin gene and dystrophin
      changes in muscle cells of the patients with Duchenne/Becker muscular dystrophy
      (DMD/BMD), furthermore to investigate the relationship between them and clinical
      symptoms. METHODS: 42 patients with DMD/BMD were screened by 9 primers multiplex
      PCR. The patients from 5 DMD and 2 BMD were detected by immunofluorescence
      technique for analyzing dystrophin located in muscle cell membrane, compared with
      2 normal males. RESULTS: The deletion of one or more exons was found in 21
      patients. 16 cases (76.2%) were detected in the central region and 5 patients
      (23.8%) in the 5' extreme region, especially in exon 48 (6 patients). Negative
      result of staining was seen in 5 DMD patients. Of these, one case of DMD had no
      detectable levels of dystrophin, but no deletion of DMD gene. Dystrophin
      immunostaining from two BMD patients consisted of a discontinuous staining
      pattern around most fibers. CONCLUSION: It might be possible that some
      correlation existed between the type of gene deletion and the degree of severity
      of the disease. The amount and size of exon deletion may not affect the symptoms.
      DMD/BMD are highly heterogeneous in clinical manifestation and in inheritance
      pattern. The pathologic foundation of DMD and BMD is the absence or abnormal
      expression of dystrophin. The consequence of that depends not only on the degree,
      but also on the function.

PMID- 21180174
TI  - [The influence of acetylcholine on N receptor beta-subunit of the gastric
      epithelia and the gastric adenocarcinoma cells].
AB  - AIM: To study the influence of acetylcholine (ACh) on nicotinic receptor(N
      receptor) beta-subunit of the gastric epithelia and the gastric adenocarcinoma
      cells, and the difference of both cells. METHODS: Immunohistochemistry method was
      used to examine the number, number density and surface density of N receptor beta
      subunit in both cells cultured in vitro. RESULTS: The number and number density
      of N receptor beta-subunit in the gastric adenocarcinoma cells were much more
      than that in the gastric epithelia (P < 0.05). But surface density of N receptor
      beta-subunit in the gastric adenocarcinoma cells were lower than that in the
      gastric epithelia (P < 0.05). ACh at 10(6) mol/L could increase the number,
      number density and surface density of N receptor beta-subunit in the gastric
      epithelia (P < 0.01). The increase effect could not be blocked by atropine. ACh
      had no effect on N receptor beta-subunit in the gastric adenocarcinoma cells.
      CONCLUSION: ACh at low concentration initiates N receptor desensitization in the
      gastric epithelia. ACh has no effect on sensitivity of N receptor beta-subunit in
      the gastric adenocarcinoma cells.

PMID- 21180175
TI  - [Experimental study on the effect of low and moderate exercise workload on IL-2
      and beta-EP in stressed rats].

PMID- 21180176
TI  - [The mechanism of protection by sound conditioning from acoustic trauma].
AB  - AIM: To investigate the mechanism of protection by sound conditioning from
      acoustic trauma. METHODS: Sound conditioning experimental model of animals was
      established. The expression of CaM, HSP70 and F-actin in hair cells were examined
      with the method of immunohistochemistry. Free calcium concentration in hair cells
      was observed by LSCM at the same time. Quantitative investigation was devised to
      assess the changes of F-actin, CaM, HSP70 and intracellular calcium concentration
      in hair cells. RESULTS: The expression of CaM, HSP70 and F-actin all showed an
      increased trend after noise exposure. HSP70 and F-actin expressed significantly
      more in group CH than that expressed in group H. Compared with group H, the
      expression of CaM showed an increased trend in group CH. Elevation of
      intracellular calcium concentration could be resulted from noise exposure. The
      calcium concentration in group H was significantly higher than that in group C
      and group CH. CONCLUSION: A suitable sound conditioning can make the auditory
      system of guinea pig more resistant to noise trauma. The strengthened
      cytoskeleton system and the intracellular calcium homeostasis play a critical
      role in the protective mechanism of sound conditioning.

PMID- 21180177
TI  - [Inhibitory effect of triptolide on proliferation of PC12 cells].
AB  - AIM: To investigate the effect of triptolide on proliferation of PC12 cells and
      the mechanism involved in the effect, and provide evidence for clinical use of
      triptolide in treatment of tumor. METHODS: By means of morphological observation,
      MTT assay, flow cytometry (FCM) and RT-PCR, the effect of triptolide on the
      proliferation of PC12 cells was observed in vitro. RESULTS: The proliferation
      inhibition was found on PC12 cells incubated with triptolide (5 x 10(3) or 25 x
      10(3) g/L) for 24 h, 48 h and 72 h, and with the higher concentration of
      triptolide, the inhibition was stronger. Low concentration of triptolide (1 x
      10(3) g/L) showed no significant effect on proliferation of PC12 cells. After
      treatment of PC12 cells with triptolide (5 x 10(3) g/L) for 24 h, increased
      percentage of G0-G1 phase and decreased percentage of S phase were found.
      Expression of translational elongation factor 2A3-2 was reduced after treatment
      of PC12 cells with triptolide (5 x 10(3) g/L). The expression of 2A3-2 was weaker
      in PC12 cells treated with triptolide for 48 h than for 24 h. CONCLUSION:
      Triptolide inhibits the proliferation of PC12 cells. The inhibition may be
      realized by changing the expression of 2A3-2 and preventing the transition from
      G0-G1 phase to S phase.

PMID- 21180178
TI  - [The effects of aging on high frequency oscillations of median nerve
      somatosensory-evoked potentials in human].

PMID- 21180179
TI  - [Establishment of a method for determining the sphingosine kinase activity and
      its initial application].
AB  - AIM: To establish the methods for determining the activity of sphingosine
      kinase(SPK) and the content of sphingosine 1-phosphate (S1P) in biological
      samples. METHODS: The ECV304 cells were transfected with pcDNA3 vector encoding
      Flag-labeled SPK gene. The expression of SPK was measured by Western blot assay
      and the activity of SPK was determined by enzymatic reaction, isotope
      incorporation and thin-layer chromatography methods. The S1P in biological
      samples was extracted, digested by alkaline phosphatase and then catalyzed by
      SPK. The S1P contents were determined according to the amounts of products.
      RESULTS: SPK gene transfection could enhance the expression and activity of SPK
      in cells markedly, and the cellular S1P was also increased obviously. HGF
      stimulation could increase the activity of SPK and cellular S1P in ECV304 cells.
      CONCLUSION: Methods for determining the activity of SPK and the content of SPK in
      biological samples were established.

PMID- 21180180
TI  - [Adult rat cardiomyocytes isolated by constant flow perfusion at low pressure].
AB  - AIM: In order to get high-yield and high-quality cardiomyocytes from adult rat.
      We needed to clarify the optimal perfusion pressure in a constant flow condition
      and stopping digestion pressure. METHODS: The rat was injected with heparin (1
      000 IU/kg, i. p.) 20 minutes prior to the experimental protocol. The heart was
      excised and the aorta was cannulated rapidly. The cannulated heart was mounted on
      a Langendorff perfusion apparatus with constant flow and perfusion pressure was
      monitored. The initial perfusion pressure was maintained at 15 kPa or 10 kPa by
      regulating the flow rate. The heart was digested by 0.08 % collagenase I at 37
      degrees C and the enzymatic digestion was terminated immediately when the
      perfusion pressure was lowered to 10 kPa, 7.5 kPa or 5 kPa. RESULTS: While the
      initial perfusion pressure was 15 kPa (n = 4), enzymatic digestion induced great
      extent increment in perfusion pressure (maximal pressure > 25 kPa). The left
      ventricle was enlarged significantly and the contractility of myocytes was
      decreased. While the initial perfusion pressure was kept at 10 kPa, the digestion
      only resulted in less extent increment in perfusion pressure (maximal pressure <
      18.75 kPa). The left ventricle was enlarged slightly. In the same initial
      perfusion pressure, if the digestion was stopped at 10 kPa (n = 3), or 5 kPa (n =
      4), myocytes appeared over much or insufficiency digestion, respectively. The
      viability of freshly isolated cardiomyocytes was less than 10%. The most of
      myocytes died after restoration of extracellular Ca2+ concentration. If the
      digestion was stopped at 7.5 kPa (n = 15). The viability of cardiomyocytes was
      82.6% +/- 4.8% in fresh isolation, 30.4% +/- 4.5% after restoration of normal
      extracellular Ca2+ concentration, or 24.8% +/- 5.4% after 4 h standing. The most
      of rod-shaped cardiomyocytes were quiescent and had visible cross striations,
      sharp edges, and normal contractility. CONCLUSION: When the initial perfusion
      pressure is kept at 10 kPa (low pressure) and the enzymatic digestion is stopped
      at 7.5 kPa, high yield and high quality cardiomyocytes can be obtained.

PMID- 21180181
TI  - [Effects on the RBC-AchE and anti-seasickness capacity in cabin environment].

PMID- 21180182
TI  - [Intensive cholesterol drug lowering: how to be sure about their safety].
AB  - Cholesterol drug lowering is a paradig on how to best apply clinical evidence to
      clinical practice. Considering the available options, it is essential that
      statins have a clear safety and tolerability profile and a favourable
      benefit/risk relationship. Intensive cholesterol drug lowering is not associated
      with deleterious consequences, dependent on a greater efficacy or on serious side
      effects. Statins are not hepatotoxic. Enzyme fluctuation is common in
      dyslipidemia. The risk of increased transaminases is directly and closely related
      to the dosage (and type of statin used). Minor changes in baseline liver profile
      are not regarded as contraindications to their use (in patients with a
      cardiovascular justifiable risk). Iterative monitoring of the liver profile is
      not necessary. The etiology of miotoxicity with statins is not completely clear.
      The risk of myopathy or rhabdomyolysis is not related to the absolute or percent
      change in the LDL-C (or with the achieved LDL-C value). The adverse effects of
      statins may depend on the physical and chemical characteristics of the molecule
      and its pharmacokinetic characteristics. On a pharmacovigilance strategy the
      patient also has his say. The sharing of a common goal makes the patient divide
      responsibilities with his Health Team, encouraging safer treatments and better
      cardiovascular prevention. The grounds for treatment and intensive effective
      reduction of dyslipidemias must be made through a better adherence to quality
      Health Programs and through improving treatment and achieved goals.

PMID- 21180183
TI  - [Troponins can fool].
AB  - The development of troponins dramatically changed the diagnosis of cardiac
      injury. Cardiac troponins are the most sensitive and specific biochemical markers
      of myocardial damage. In 2000. it was elaborated the new definition of miocardial
      infarction that reflected the importance of that biomarker. The rationale of
      including troponin assay in the diagnosis pathway was based on the assumption
      that myocardial necrosis, regardless of its magnitude, should be characterized as
      myocardial infarction. However, if the patient's clinical picture do no match an
      elevated troponin result we shoud suspect a false positive value caused by
      analytical interferences. This article ilustrates, by presentation of a case
      report, that in spite of its importance in the diagnosis of myocardial
      infarction, troponin positivity should't be the sole criterion for establishing
      such a diagnosis.

PMID- 21180184
TI  - [Value of exercise echocardiography in aortic recoarctation--case report].
AB  - In this article the authors present a case study of a young man with coarctation
      of the aorta that underwent surgical correction at 4 months old, for whom the
      exercise echocardiogram was important in determining the functional importance of
      recoarctation and the decision of the timing for re-intervention, demonstrating
      the importance of this technique to discriminate the functional significance of
      this pathology.

PMID- 21180185
TI  - [Double orifice mitral valve: an incidental finding in a patient with other
      congenital malformations].

PMID- 21180186
TI  - [Stress perfusion cardiac MRI: a new tool in the evaluation of myocardial
      ischemia].

PMID- 21180187
TI  - [Nursing profession, future reforms].

PMID- 21180188
TI  - [First look and early attachment of the newborn].

PMID- 21180189
TI  - [Accompanying maternal breast feeding].

PMID- 21180190
TI  - [Caring for children in the face of social mutations].
AB  - In 50 years, as a result of works on hospitalism, attachment and intelligence of
      babies, the latter have gradually gone from being considered as vegetative beings
      to being seen as a person. A new model of socialisation has appeared which sees a
      wide variety of players confronted with contemporary social mutations and which
      is changing professional and parenting practices.

PMID- 21180191
TI  - [Parenting, a concept in question].
AB  - Since the 1980s, a number of parenting support actions have been developed, with
      significant involvement from those working in early child care and education.
      This notion is based on the construction of a parent-professional partnership
      around the child, in which everyone is involved.

PMID- 21180192
TI  - [Child care nurse, looking back at the past in order to build the future].
AB  - Child care nurses, just like other nursing specialities, are involved in a
      descriptive as well as a prospective reflection of the contribution they make in
      the area of healthcare. A look back at this nursing speciality provides a better
      understanding of the issues involved and opens up the perspectives of this
      reflection.

PMID- 21180193
TI  - [Training of child care nurses, evolution and challenges].
AB  - The novelty of the reform of the nursing training programme lies in the fact that
      it focuses on skills development. The training of child care nurses is also due
      to be reformed in the months to come. A different concept, an evolution, the
      influence of pedagogical trends: an assessment of the reform in progress.

PMID- 21180194
TI  - [The development of home visiting by child care nurses].
AB  - Child care nurses play a crucial role in the care of children and their families
      at home. In addition to carrying out prescribed technical care, they also have a
      role to play in health promotion and education. An important part of the
      healthcare provision, the independent child care nurses' work is part of a
      multidisciplinary approach.

PMID- 21180195
TI  - [Development of experienced pediatric nurses, accounts of experiences].

PMID- 21180196
TI  - [What is the outlook for specialization in child care?].

PMID- 21180197
TI  - [Elements of bibliography. Books].

PMID- 21180198
TI  - [The role of the nurse in paediatric haemodialysis].
AB  - The care provided in paediatric haemodialysis is highly technical. The relational
      and educational aspect is also essential for the success of the considerable and
      almost daily monitoring of the children. Support is given to these children by
      nurses working within a multi-disciplinary team.

PMID- 21180199
TI  - [Burns in a child].

PMID- 21180200
TI  - [The regulatory framework of adoption].

PMID- 21180201
TI  - Models of nursing/midwifery and patterns of work.

PMID- 21180202
TI  - Why have workload management tools?

PMID- 21180206
TI  - Information about articles retraction.

PMID- 21180204
TI  - An end to witch trials in Austria: reconsidering the enlightened state.

PMID- 21180207
TI  - Consultation meeting on tuberculosis and diabetes mellitus:  meeting summary and
      recommendations.
AB  - The steadily growing epidemic of diabetes mellitus (DM) poses a threat for global
      tuberculosis (TB) control. Previous studies have identified an important
      association between DM and TB. However, these studies have limitations: very few
      were carried out in low-income countries, and none in Africa, raising uncertainty
      about the strength of the DM-TB association in these settings, and many critical
      questions remain unanswered. As a result of these questions and uncertainties,
      the International Union Against Tuberculosis and Lung Disease (The Union), the
      World Diabetes Foundation and the World Health Organization Stop TB Department
      undertook a series of consultations as of January 2009. A systematic review and
      meta-analysis was undertaken by the Department of Epidemiology, Harvard School of
      Public Health between May and August 2009, and a consultation meeting involving
      the experts who reviewed the report took place at The Union Headquarters in Paris
      on 6 and 7 November 2009. This paper constitutes a summary report of the
      findings, the research gaps and prioritised areas of research, and the
      recommendations from that meeting.

PMID- 21180208
TI  - Answer quiz vil 12 no.1. Left laterocervical mass in a 2 month old newborn.
      Diagnosis: Fibromatosis colli.

PMID- 21180209
TI  - [The 18th International Congress of Endoscopic Surgery. Geneva, June 16-19,
      2010].

PMID- 21180210
TI  - Is routine conventional biopsy sufficient for thorough histological evaluation of
      a neoplastic lesion?

PMID- 21180211
TI  - Pattern of breast cancer in a tertiary care center.
AB  - INTRODUCTION: Breast Cancer is the second commonest cause of cancer death in
      women. Almost all women survive breast cancer if it is detected before it starts
      to spread. The aim of the study is to analyze the demographical profile, stage of
      presentation, histological type, and treatment modalities of breast cancer in a
      tertiary care setting. METHODS: Total 1141 cases of breast cancer had been
      followed retrospectively from 1999 to 2006 A.D. in a tertiary care center and
      their patterns were analyzed. RESULTS: The mean age of presentation of breast
      cancer was 47.30 +/- 11.57 years in female and 59.03 +/- 14.63 in male, 31 (2.1%)
      cases of breast cancer were male. There were 123 (10.78%) stage I, 281 (24.62%)
      stage II, 466 (40.84%) stage III, and 271 (23.75%) stage IV patients.
      Infiltrating ductal carcinoma was the commonest variety 610 (53.5%). Chemotherapy
      was the mainstay for treatment of breast cancer 341 (29.9%) followed by surgery
      287 (25.2%). CONCLUSIONS: Breast cancer trend is rising with more in late and
      advanced stages, mostly due to lack of awareness. Infiltrating ductal carcinoma
      is the commonest variety. Chemotherapy is the most commonly used modality of
      treatment. Male breast cancer present late and is not so uncommon.

PMID- 21180212
TI  - Practices and results of two years service from a single U.K. renal transplant
      center.
AB  - INTRODUCTION: End stage renal failure is a common condition requiring renal
      replacement therapy in the form of haemodialysis or peritoneal dialysis as a
      short-term measure with renal transplantation as a more definitive treatment
      option. The aim of this study was to evaluate the set up of a renal transplant
      unit in a developed country and compare its results with other centers of the
      world. METHODS: A retrospective observational study was conducted to see the
      results of two years activities of a well known renal transplant unit in the
      United Kingdom. A description of the setup of a renal transplant unit has been
      made and its results have been discussed. RESULTS: Of the total patients, who had
      transplants in the renal transplant unit in year 2006 and 2007, 209 were renal,
      14 were simultaneous kidney pancreas and two were pancreas after kidney
      transplants. Our one year graft survival rate was 93%, delayed graft function was
      15%, early rejection rate was 11% and mortality rate was 3% in one year follow
      up. CONCLUSIONS: To attain good results in renal transplantation surgery, a multi
      disciplinary team approach is crucial. Our set up is an example where the results
      are comparable to published and unpublished data from other established units
      world-wide.

PMID- 21180213
TI  - Trend of complete hydatidiform mole.
AB  - INTRODUCTION: Complete Hydatidiform mole is one of the most frequent abnormal
      pregnancies. This review studies the trend of complete mole in Paropakar
      Maternity and Women's hospital and clinical ability to detect it. METHODS: This
      is a retrospective study of 504 cases of complete hydatidiform mole recorded at
      Paropakar maternity and women's hospital, Kathmandu, during 2058-2065 B.S.
      Medical records were reviewed and incidence, clinical presentation and method of
      diagnosis were studied. RESULTS: During the study period, there were 13,9117
      births and 504 complete moles, 12 partial moles, 48 persistent gestational
      tumours, six choriocarcinoma and four invasive moles recorded in the hospital.
      The incidence of complete mole was one per 276 births. It was prevalent among
      women younger than 29 years (80%) and among the primigravidae (36.7%). More than
      90% women presented in the first half of their pregnancy and vaginal bleeding was
      the main complaint (68.3%). Suction evacuation, dilation and evacuation followed
      by sharp curettage and abdominal hysterectomy were performed in 80.6%, 17.6% and
      1.2% of the women respectively. Persistent mole and choriocarcinoma developed in
      9.5% and 0.4% respectively. CONCLUSIONS: Complete mole has the highest incidence.
      It affects mostly younger women and presents with vaginal bleeding most of the
      time, usually in the first half of their pregnancy.

PMID- 21180214
TI  - Stress, autonomic reactivity and blood pressure among undergraduate medical
      students.
AB  - INTRODUCTION: Medical training is highly stressful particularly for those who are
      beginning their medical education. The present study was undertaken to find out
      the level of stress, hypertension and its etiological factors among undergraduate
      medical students. METHOD: One hundred and seventeen undergraduate medical
      students between 17-21 years of age got examined for blood pressure and stress
      level. Twelve hypertensives selected from the above subjects and twenty
      normotensives underwent cold pressure test to assess autonomic reactivity to
      laboratory induced stress. RESULTS: 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
      both the hypertensive and normotensive group but came back to basal levels within
      5 minutes indicating normal autonomic response. Rise of BP was higher in
      hypertensive group. The diastolic and mean BP increased significantly on CPT in
      subjects having family history of hypertension. The subjects taking more of junk
      and oily foods had a higher systolic BP. Forty percent of normotensive subjects
      had more than 20 mm Hg rise in systolic BP on CPT. CONCLUSIONS: Adolescents must
      be routinely screened to detect asymptomatic hypertension. Advice on risk factor
      modification by appropriate lifestyle changes may prevent long term effects of
      hypertension on target organs.

PMID- 21180215
TI  - Unsafe abortion: a tragic saga of maternal suffering.
AB  - INTRODUCTION: Unsafe abortion is a significant cause of maternal morbidity and
      mortality in developing countries despite provision of adequate care and
      legalization of abortion. The aim of this study was to find out the contribution
      of unsafe abortion in maternal mortality and its other consequences. METHODS: A
      retrospective study was carried out in the Department of Obstetrics and
      Gynecology in BPKIHS between 2005 April to 2008 September analyzing all the
      unsafe abortion related admissions. RESULTS: There were 70 unsafe abortion
      patients. Majority of them (52.8%) were of high grade. Most of them recovered but
      there were total 8 maternal deaths. CONCLUSIONS: Unsafe abortion is still a
      significant medical and social problem even in post legalization era of this
      country.

PMID- 21180216
TI  - Comparison of bolus phenylephrine, ephedrine and mephentermine for maintenance of
      arterial pressure during spinal anesthesia in cesarean section.
AB  - INTRODUCTION: Hypotension is common following spinal anesthesia. Various
      vasopressors have been indicated to prevent it. The study compares three such
      agents namely phenylephrine, ephedrine and mephentermine. METHODS: The study
      included 90 patients undergoing elective and emergency cesarean section who
      developed hypotension following subarachnoid blockade. Parturient were randomly
      divided into three groups each group had 30 patients. Group P received bolus of
      Phenylephrine 25 microgram, where as group E received Ephedrine 5mg and Group M
      received Mephentermine 6mg. RESULTS: It was found that rise of blood pressure was
      significantly higher in case of phenylephrine group in first six minutes, after
      the bolus, there was significant reduction in the heart rate in phenylephrine
      group, but there was tachycardia following administration of bolus ephedrine and
      mephenteramine. Neonatal APGAR score were similar in all three groups.
      CONCLUSIONS: All three drugs maintained hemodynamics within 20 percent of the
      baseline values on intravenous administration.

PMID- 21180217
TI  - Ocular morbidity among orphanages.
AB  - INTRODUCTION: The study assesses the spectrum of ocular morbidity and predictors
      of morbidity in children living in orphanages in the Kathmandu Valley. METHODS: A
      descriptive, cross-sectional survey was performed at 12 orphanages over a period
      of three months. The survey included a questionnaire and a complete eye
      examination, which included measurement of refraction, ocular deviation, and a
      fundus exam. Prevalence of ocular morbidity was calculated. Factors associated
      with ocular morbidity were examined using logistic regression. RESULTS: A total
      of 660 children were included in the study (median age nine years [range 0.25
      15]; 53% male). The prevalence of ocular morbidity was 17.9% (118). Of those with
      ocular morbidity, 88.1% (104) had similar ocular problems bilaterally. The most
      common type of morbidity was refractive error, found in 70.3% (83) of those with
      ocular morbidity (12.6% overall). CONCLUSIONS: Refractive errors, which are
      largely correctable, are the greatest source of morbidity. In order to reduce
      childhood blindness, children living in orphanages are an appropriate group to
      target for future ocular screening in Nepal.

PMID- 21180218
TI  - Safety and efficacy of misoprostol and dinoprostone as cervical ripening agents.
AB  - INTRODUCTION: The study compares safety and efficacy of misoprostol and
      dinoprostone as cervical ripening agents. METHODS: Patients with term, vertex,
      singleton pregnancy and Bishop score of 4 or less were randomly assigned to
      receive misoprostol pessary (n=35, 50 microg intravaginally) or dinoprostone gel
      (n=31, 0.5 mg intracervically) at 6 hourly intervals. If there were no progress
      in cervical dilatation or effective uterine contraction even after maximum dose,
      patients were taken for cesarean section. Patients who achieved Bishop's score
      more than 7 but the delivery was not progressing, were augmented with oxytocin
      drip. RESULTS: No uterine hyperstimulation was observed in both groups. However,
      abnormal fetal heart rate was observed in 3(8.6%) cases in misoprostol group and
      2 (6.5%) in dinoprostone group. There was no statistically significant difference
      in meconium passage in two groups. Apgar score less than 7 at 1 minute was seen
      in 6 (19.4%) and 11 (31.4%) neonates in dinoprostone and misoprostol group
      respectively. However Apgar score less than 7 at 5 minutes was found in only one
      neonate of dinoprostone treated patient. Both drugs were found to be equally
      effective in improving Bishops score with no significant difference in mean
      induction to delivery time. Cesarean section was done among 32.3% and 28.6%
      respectively in dinoprostone and misoprostol groups. There was significant
      reduction in the need for oxytocin augmentation in misoprostol (37.1%) group than
      in dinoprostone (67.7%) group. CONCLUSIONS: Vaginal misoprostol is an effective,
      safer and cheaper alternative to dinoprostone as a cervical ripening agent in
      underdeveloped countries.

PMID- 21180219
TI  - Outcome of extracorporeal shock wave lithotripsy at B and B Hospital.
AB  - INTRODUCTION: Extracorporeal Shock Wave Lithotripsy is an effective noninvasive
      method to treat urolithiasis. This study aims to evaluate its outcome and
      determine appropriate management strategies for urolithiasis. METHODS: It was a
      prospective study which included one hundred patients who underwent ESWL for the
      management of solitary urolithiasis during a period of eight months (December
      2007-August 2008). Status of stone and complications were observed and managed
      accordingly within a period of six postoperative weeks. RESULTS: Out of 100
      patients, 93% had complete clearance of stone by the end of six postoperative
      weeks. Seven percent of the patients required adjunct invasive intervention
      including open surgery in 3%. Number of sessions of ESWL was found to increase as
      the size of stone increased. However, in three patients stones were completely
      refractory to ESWL even after two consecutive sessions. CONCLUSIONS: ESWL is
      highly effective noninvasive modality in the management of urolithiasis in
      appropriately selected patients.

PMID- 21180220
TI  - Refractive error, strabismus and amblyopia in congenital ptosis.
AB  - INTRODUCTION: Congenital ptosis is often associated with visual impairment. The
      aim of the study is to find out the pattern of refractive error, strabismus and
      amblyopia in patients with congenital ptosis in a hospital setting. METHODS: This
      is a hospital based prospective and descriptive study conducted at Tribhuvan
      University, B P Koirala Lion's Centre for Ophthalmic studies in Nepal from
      February 2003 to July 2004. All the consecutive cases with congenital ptosis were
      included and cases with pseudoptosis were excluded from the study. RESULTS: Among
      the 78 cases (95 eyes) of congenital ptosis, refractive error was present in 13
      cases (16.7%) with astigmatism as the commonest refractive error (8.9%).
      Strabismus was found in 23 cases (26.9%) of congenital ptosis. Among the
      strabismus, combined exotropia with hypotropia was found in the majority of cases
      (16.7%). Visual impairment due to amblyopia was found in 15 cases (19.2%) of
      congenital ptosis with mixed strabismic and refractive etiology as the commonest
      one (46.7%) followed by pure strabismic (26.7%), pure refractive (20%) and
      stimulus deprivation amblyopia (6.7%). CONCLUSIONS: Patients with congenital
      ptosis have higher rate of amblyopia due to greater prevalence of strabismus and
      refractive errors although stimulus deprivation amblyopia is less common. Early
      ophthalmic evaluation and timely treatment of these conditions may help prevent
      the irreversible visual impairment in case of congenital ptosis.

PMID- 21180221
TI  - Endoscopic grading of adenoid in otitis media with effusion.
AB  - INTRODUCTION: Adenoid is thought to be one of the causes of otitis media with
      effusion, though it is controversial. Grading the adenoid by rigid nasal
      endoscope in patients with otitis media with effusion may justify adenoidectomy
      in otitis media with effusion in the future. METHODS: A prospective study was
      carried out at GMS Memorial Academy of ENT and head neck studies from 15th
      December 2005-April 2007. Study group comprised of 32 children with otitis media
      with effusion and control group of 28 children with clinically normal ear and
      nose. Rigid nasal endoscope was used for grading of adenoid in study and control
      group. The severity of otitis media with effusion was assessed by preoperative
      air-bone gap and thickness of the fluid aspirated from middle ear during
      ventilation tube insertion. RESULTS: In the study group 13 out of 32 had grade 4
      adenoid hypertrophy. This grade 4 adenoid hypertrophy was found to be
      statistically significant in children with otitis media with effusion (P <
      0.0002). In control group 15 out of 28 had grade 1 adenoid hypertrophy which was
      significant in the same group (P < 0.002). Air-bone gap and thickness of fluid
      did not correlate with the increasing grade of adenoid hypertrophy. CONCLUSIONS:
      Grade 4 adenoid hypertrophy was statistically found to be significant with otitis
      media with effusion but severity of hypertrophy were not reflected by hearing
      loss and thickness of fluid.

PMID- 21180222
TI  - Ovarian pregnancy: a rare ectopic pregnancy.
AB  - Primary ovarian pregnancy is a rare entity, the incidence being 1 in 25,000 to
      40,000 pregnancies. The diagnosis is difficult and still continues to challenge
      the clinicians. A case of ovarian pregnancy is reported here. The patient
      underwent laparotomy with right sided oophorectomy. Histopathological examination
      confirmed it to be an ovarian pregnancy.

PMID- 21180223
TI  - Deep vein thrombosis in protein S deficiency.
AB  - Protein S is a vitamin K-dependent anticoagulant protein. It functions as a
      cofactor of activated protein C to inactivate activated factor V (FVa) and
      activated factor VIII (FVIIIa). Its deficiency is a rare condition and can lead
      to deep vein thrombosis, pulmonary embolism or stroke. It is often treated with
      long-term anti-coagulant therapy. Protein S deficiency may be hereditary or
      acquired; the latter is usually due to hepatic diseases or a vitamin K
      deficiency. Protein S deficiency manifests as an autosomal dominant trait;
      manifestations of thrombosis are observed in both heterozygous and homozygous
      genetic deficiencies of protein S. This case report is of DVT due to Protein S
      deficiency in a 53 year old male. Venous Doppler was used to diagnose DVT and
      free Protein S level measured by ELISA. IVC filter was placed on the third day of
      admission.

PMID- 21180224
TI  - Intracranial aneurysm with systemic lupus erythematosus treated by endovascular
      intervention.
AB  - Systemic lupus erythematosus (SLE) is a chronic disease with multiple pathologies
      that can affect every organ system of the body including central nervous system.
      Intracerebral aneurysms and subarachnoid hemorrhage (SAH) are one of
      comparatively rarer manifestations of central nervous system SLE. Here we present
      a case of known SLE complicated by the rupture of intra cerebral aneurysm at
      basilar artery tip which was successfully treated with endovascular coiling.

PMID- 21180225
TI  - Tamoxifen for breast cancer.
AB  - Breast cancer is one of the common cancers. Hormonal therapy along with surgery,
      chemotherapy, radiotherapy and targeted therapy are vital modalities for the
      management of breast cancer. Tamoxifen has been the most widely used hormonal
      therapy for more than two decades. In this article we review the benefits, dose,
      duration and timing of Tamoxifen therapy in patients with breast cancer.

PMID- 21180226
TI  - Learning pelvic examination with professional patients.
AB  - Performing pelvic examination is a vital skill to learn during gynecological and
      obstetrical training. It's a difficult maneuver to master as there is very little
      to see and more to feel and interpret. In addition, learning PE in usual clinical
      set-up has been found to induce lot of stress and anxiety among both the patients
      and the students. Students fear of hurting the patients and being judged inept,
      whereas patients feel embarrassed having to expose their most intimate body parts
      for learning purpose. This hampers effective learning. Learning PE on sedated
      women before surgery or on mannequins has been practiced as alternative learning
      models. But, they have been found to miss out on teaching the communication
      skills, which are as important as the palpation skills. However, there exists
      another model of learning PE--the professional patients, who are specially
      trained to act as patients and also guide the students on how to make a proper
      PE. They provide stress-free environment for the students to learn PE and at the
      same time, provide immediate feedback on each of their maneuvers. They form a
      complete learning model and help students to see patients as partner and not just
      a person seeking help.

PMID- 21180227
TI  - Ten PM note of organophosphate poisoning: successful outcome of a medical audit
      with complete seven steps.
AB  - Medical audit in general consists of seven steps like choosing topic, setting
      criterion and standard, collecting first data, comparing data with standard,
      introducing change, collecting second data and reflecting. Its three basic
      premise are improvement of patient care by using existing knowledge, team work
      with ongoing educational process and change management and promotion of blame
      free culture maintaining confidentiality. Audit mostly relates to a particular
      practice and is therefore not generalisable. An audit of residents' late evening
      routine notes of organophosphate poisoning patients is reported here, as the
      change introduced appears relevant to the situation of developing countries.
      Organophosphate poisoning patients should be managed in intensive care unit with
      close monitoring, as inadvertent stoppage or slowing of atropine infusion may
      occur, particularly at night, leading to reappearance of poisoning
      manifestations, which may cause respiratory failure and death. If they are
      managed in wards, residents-on-duty can check the clinical and intravenous drip
      status in the late evening and communicate with nurses and relatives to be
      particularly vigilant. In the audit done, such regular ten pm notes of
      organophosphate poisoning about the clinical and drip status and communication by
      residents were increased from 15.5% in the first to 81.7% in the second data
      collection (p < 0.01) after the introduction of the change. The ten pm note is
      being continued for about two years now. Implementation of ten pm note of
      organophosphate poisoning patients admitted in medical wards is feasible and
      appears useful to improve the quality of health care delivery and learning of
      residents.

PMID- 21180228
TI  - Risk factors associated with still births.
AB  - INTRODUCTION: Still birth is a common adverse outcome of pregnancy, associated
      with many risk factors like prematurity, infection, birth injury, eclamptic
      disorders. METHODS: A hospital based, retrospective study was conducted at Patan
      Hospital in the year 2064. The number of still births and their associated risk
      factors were assessed. RESULTS: There were three thousand and five hundred and
      eighty eight deliveries. Among all deliveries, still birth cases were counted
      forty seven with a rate of 14 per thousand deliveries. The major risk factors
      were prematurity, low birth weight, fetal distress and maternal jaundice.
      CONCLUSIONS: Prematurity was the commonest risk factor for still birth.

PMID- 21180229
TI  - Education of adolescents on reproductive health: which way to go?
AB  - INTRODUCTION: The study was done to assess the educational needs of the
      adolescent girl students regarding their reproductive health. METHODS: The data
      were collected by administering an open-ended self-administered questionnaire to
      the participating students seeking their opinion on several issues related to
      adolescent reproductive health. RESULTS: The students preferred their teachers
      next only to doctors as health educator. Their health problems included menstrual
      problems, weakness, eye problems, headache and weight gain. Other problems were
      tension with studies, inability to concentrate, depression and irritability. Two
      most important areas of their concern are safe motherhood and AIDS. CONCLUSIONS:
      Need exists for reproductive health education.

PMID- 21180230
TI  - SILCAAT and ESPRIT: taking stock.

PMID- 21180231
TI  - HIV immunology: what lessons can we learn from recent vaccine trials?

PMID- 21180232
TI  - Lymphocyte activation in HIV-1 infection: time for quality control.

PMID- 21180233
TI  - A review of the use of activation markers in Africa.

PMID- 21180234
TI  - Implications of the SILCAAT and ESPRIT trials and the future for HIV
      immunotherapy.

PMID- 21180235
TI  - Treatment of extrahepatic manifestations of chronic hepatitis C viral infection-
      a challenge.
AB  - Often, chronic hepatitis C infection is clinically manifested as extra hepatic
      disease. Therapy of the extra hepatic manifestations (EHM) is always difficult
      and based on the optimal and individual association of antiviral treatment,
      immunosuppressant and plasma cleaning techniques. We observed for 4 years 246
      patients admitted to "Colentina" Internal Medicine Clinic, of whom 168 were
      diagnosed as chronic C hepatitis. 130 of those patients have had at least one
      EHM. In our experience, the presence of an EHM is significantly correlated with
      lack of early viral response and sustained viral response, as well.
      Cryoglobulinemic vasculitis needs to be treated with oral or pulse corticotherapy
      associated to plasmapheresis. When present, peripheral neuropathy and cryocrit
      greater than 10% are indicators of need of more than 3 plasmapheresis sessions.

PMID- 21180236
TI  - Functional dyspepsia: a pragmatic approach.
AB  - Functional dyspepsia includes one or more of four cardinal symptoms: postprandial
      fullness, early satiety, pain or burning in the epigastrum. According to the Rome
      III diagnostic criteria for functional dyspepsia, these symptoms must be present
      for the last 3 months with symptom onset at least 6 months prior to diagnosis.
      Functional dyspepsia is not the result of an underlying structural abnormality,
      but rather the consequence of multiple pathophysiological mechanisms such as
      abnormal gastric motility, gastric and duodenal hypersensitivity to acid,
      Helicobacter pylori infection. Dyspeptic patients over 50 or those with alarm
      symptoms should be investigated to detect any structural abnormality such as
      cancer, peptic ulcer or esophagitis. After structural abnormalities and
      gastroesophageal reflux disease are excluded the management of functional
      dyspepsia consists of either a test and treat approach (non invasive detection of
      Helicobacter pylori infection followed by eradication therapy) or empirical
      therapy. Although endoscopy was traditionally reserved for those patients without
      symptom relief after 6-8 weeks of therapy, the significant percentage of patients
      with functional dyspepsia with symptom breakthrough or relapse after
      antisecretory or prokinetic therapy discontinuation makes an initial endoscopic
      study a logical choice. Therapy with proton pump inhibitors yields results
      especially in those patients with regurgitation and epigastric burning sensation,
      while prokinetic agents with no extrapyramidal side effects (such as Domperidone
      and Itopride) alleviate satiation, bloating and nausea by accelerating gastric
      emptying. Second-line drugs with encouraging results in clinical trials which can
      be used in functional dyspepsia are low-dose tricyclic antidepressants as well as
      selective serotonine reuptake inhibitors.

PMID- 21180237
TI  - Immune compartments of the nephron in relation to the immune system.
AB  - The paper presents data regarding the compartmentalization of the nephron related
      to immune processes taking place at this level. The morphofunctional compartments
      of the nephron (glomerular, tubulo-interstitial and juxtaglomerular) become
      immune compartments during immune processes. The paper shows the immune cells
      located in the morphofunctional compartments of the nephron and the relationship
      between them. It is considered that the presence of immune cells in these
      compartments is a dynamic process; the number of infiltrating cells is reduced
      under physiological conditions and increases during pathological immune
      processes. The paper presents also the resident cells of the nephron and their
      immune capabilities. It also presents the professional immune cells originating
      in the bone marrow, which are involved in immune processes. The complex
      relationship between these cells by means of the cytokine network, chemokines as
      well as other mediators, as well as the role of immune receptors, mainly Toll
      like receptors is outlined. During an immune aggression immune aggregates defined
      as tertiary lymphoid organs are formed at the level of the nephron. These
      lymphoid follicle-like structures might represent an intrarenal immune system.
      The compartmentalization of the nephron is part of the recently described concept
      of compartmentalization of the immune system.

PMID- 21180238
TI  - Four hundred meters walking test in the evaluation of heart failure patients.
AB  - The best evaluation of the severity and prognosis of heart failure patients is
      obtained by the maximal exercise stress testing, but for the very large number of
      HF patients and for evaluation of their daily effort capacity submaximal stress
      testing, mainly 6 minutes walking test are used. The limit of 6mWT is that during
      it the patients are not motivated to walk and also, the periphery, so important
      for heart failure patients, is not equally involved. OBJECTIVE: To compare a new
      fixed walking test-400m walking test with 6MWT and maximal exercise testing.
      METHODS: There were investigated 20 patients with dilated cardiomyopathy (DCM).
      The patients were included in the study after the relief of the congestive
      syndrome. Each patient was submitted in three consecutive days to a maximal
      symptom-limited exercise stress test on cycloergometer, a six minutes walking
      test, a 400 meters walking test. The last one consisted of walking on a corridor
      40 meters long, at a speed chosen by the patient himself. The results were
      expressed in seconds representing the necessary time to cover the established 400
      meters of distance. RESULTS: During cycloergometer exercise stress test the
      calculated mean peak VO2 was 15.2 +/- 1.4 mlO2/kg/min (4.32 METs). The mean
      distance walked during 6MWT was 350 +/- 34m and the mean time needed to walk 400m
      (400mWT) was 300 +/- 27 seconds. The correlation between peak VO2 and distance
      walked during 6MWT was -0.40, a similar but negative value (r = -0.42) being
      registered between peak VO2 and time registered during 400mWT. Only weak
      correlation was registered between LVEF and all the three tests. In turn the
      correlation between distance registered during 6MWT and time registered during
      400mWT was excellent: r = -0.60. CONCLUSION: 400mWT is a useful tool for the
      evaluation of submaximal effort capacity of CHF patients. Its value to evaluate
      exercise capacity is similar with that of the 6 MWT, but 400mWT can assure a
      better evaluation of peripheral involvement.

PMID- 21180239
TI  - The effect of very short duration acute physical exercise upon adiponectin and
      leptin in overweight subjects.
AB  - BACKGROUND: Adiponectin is decreased and leptin increased in overweight subjects.
      In turn, exercise has controversial effect upon adiponectin and leptin plasmatic
      levels. PURPOSE: To study the effect of acute exercise upon plasmatic levels of
      adiponectin and leptin in normal and overweight subjects. METHOD: We studied 79
      subjects, 42 males and 37 females, aged 56 +/- 9 years, divided into two groups.
      Group I consisted of 19 patients with body mass index (BMI) < 25 kg/(m)2 and
      group II consisted of 60 overweight subjects (BMI > 25 kg/(m)2). All subjects
      were submitted to a maximal symptom limited exercise stress testing on
      cycloergometer, upon classical protocols (mean effort 103 +/- 27 Ws). Venous
      blood samples were obtained before exercise (sample I) and at 30 minutes after
      the effort was stopped (sample II); adiponectin and leptin levels were
      determined, using ELISA method. RESULTS: At rest adiponectin is significantly
      decreased and leptin increased in overweight subjects. In turn, during exercise
      the values of the two adipokines were not significantly different from those
      registered at rest in both groups, even if the adiponectin remained at a low
      level and leptin decreased at the limit of significance in overweight subjects.
      Considering men and women, the data are similar for men but, after exercise,
      overweight women registered a significant reduction of the leptin values. Also at
      rest adiponectin levels are more increased in overweight women (p = 0.01). This
      suggests that overweight women can be protected in comparison with men and
      exercise could add a supplementary benefice. CONCLUSION: Acute exercise has
      little effect upon adiponectin and leptin levels, but rest adiponectin is
      increased and leptin significantly decreased during exercise in overweight women
      and could be beneficial to this category of subjects.

PMID- 21180240
TI  - Evaluation at patients with ventricular arrhythmias and coronary artery disease
      of myocardial revascularization effects.
AB  - The aim of this study was to determine the relations between myocardial
      revascularization therapy--coronary artery bypass graft (CABG) and coronary
      angioplasty (PTCA)--and ventricular potentially malignant arrhythmia (VPMA)
      (coupled VPC, VPC > 10/hour, NSVT--Morganroth classification), in patients (pts)
      with stable CAD. METHODS: 765 patients with stable angina and ventricular
      potentially malignant arrhythmia were evaluated angiochoronarographically,
      echographically, by programmed electrical stimulation (PES), standard ECG, Holter
      ECG, radiologically, and by stress test. From 765 patients with CAD and VPMA 169
      pts. (22.9% of cases) were revascularized, 77 pts. (10.06% of cases) by CABG
      surgery and 82 pts. (10.71% of cases) by PTCA with or without stenting. RESULTS:
      From pts. with inducible sustained ventricular tachycardia by programmed
      electrical stimulation PES + (129 pts. 16.86% of cases), 19 pts. (2.5% of cases)
      were with CABG vs 9 pts. (1.17% of cases) with PTCA (p > 0.05). In 333 pts. with
      arrhythmogenic myocardic ischemia detected by Holter ECG/24 hours (Holter +) the
      distribution of myocardial revascularization was similar (40 pts., 5.22% of cases
      with CABG vs 46 pts., 6.01% of cases with PTCA) (p > 0.05). The study included
      225 pts. with positive stress test, 45 pts. were revascularized, 18 pts. (2.35%
      of cases) with CABG and 27 pts. (3.52% of cases) with PTCA (p > 0.05).
      Revascularized pts. represent an increased percent with prior myocardial
      infarction in the subgroup with CABG vs. PTCA (39% of cases, p < 0.05 vs. 25% of
      cases, p < 0.05). Revascularized pts. presented similar distributions of VPMA in
      subgroups with CABG and PTCA. CONCLUSIONS: VPMA was not influenced by myocardial
      revascularization, CABG or PTCA, the incidence being similar (50.94% vs 47.2%; p
      < 0.05) with pts. drug treated.

PMID- 21180241
TI  - Platelet histogram indices and cardiovascular disease in patients with rheumatoid
      arthritis.
AB  - BACKGROUND; Previous studies reported the increased prevalence of cardiovascular
      disease (CVD) in patients with rheumatoid arthritis (RA) compared to the general
      population. However, the predictors for the development of CVD in patients with
      RA were not clearly established, and the role of thrombosis mechanisms was
      inconsistently characterized in these patients. The aim of this study was to
      evaluate the platelet histogram indices, as markers of platelet activation, in
      patients with RA with or without CVD. MATERIAL AND METHODS: In 64 pts with RA
      (mean age: 58.0 +/- 12.7 yrs) we performed the standard clinical evaluation and
      biochemical workup with platelet histogram, including mean platelet volume (MPV)
      and platelet distribution width (PDW) as markers of platelet activation. We
      divided the study population into two groups: A - 41 patients with RA without CVD
      and B - 23 patients with RA and CVD (ischemic heart disease, peripheral artery
      disease or cerebrovascular disease). The values of MPV and PDW were also analyzed
      in an age- and sex-mached control group of 20 subjects without RA and CVD and in
      a group of 62 patients with CVD without RA (stable angina). RESULTS: The
      platelets number was similar in both groups, but the platelet histogram showed
      higher values for MPV (9.6 vs. 8.6 fL, p < 0.01) and PDW (16.1 vs. 14.0, p <
      0.01) in patients with RA and CVD, reflecting greater platelet activation in
      these patients. MPV values were lower in patients with RA, but the values of PDW
      were higher in these patients comparing to control. Patients with RA with CVD
      have higher values of PDW than patients with CVD, but without RA, showing an
      increased platelet activation in RA. The PDW values correlate with fibrinogen
      (0.63; p = 0.003) but not with CRP or ESR, while the MPV was not correlated with
      the inflammatory markers in patients with RA. CONCLUSIONS: The pathogensis of CVD
      in patients with RA may be linked to an increased prothrombotic activity which
      might be evaluated by platelet histogram indices.

PMID- 21180242
TI  - Professional stress and inflammatory markers in physicians.
AB  - Recent changes in society might increase stress perception in physicians. The Job
      Content Questionnaire (JCQ) is a widely used self-reported instrument to measure
      psychosocial characteristics of jobs. The biological pathways through which
      professional stress might increase cardiovascular disease risk are better
      explained nowadays. The objectives of this study were: to determine the
      connection between professional stress evaluated with Job Content Questionnaire,
      in a group of physicians, and some bioumoral markers, including cortisol, and to
      analyse gender differences. MATERIAL AND METHODS: There were included 118
      presumed healthy physicians from Cluj county, aged between 30 and 60 years, with
      medical specialites. All the results were analyzed and compared by means,
      standard deviations and alpha coefficients of validity. Were measured the
      following bioumoral markers: total cholesterol, triglycerides, HDL-cholesterol,
      fasting plasma glucose, fibrinogen, high sensitivity-CRP, and serum cortisol.
      Serum cortisol levels were measured in the morning (between 8.00-9.00 am).
      RESULTS AND DISCUSSION: 12% of the total group had fasting plasma glucose over
      the normal range, 26% had total cholesterol over 200 mg/dl, 8% had triglycerides
      over 150 mg/dl, 6% had HDL-cholesterol under the protection limits, 24% had
      elevated fibrinogen values, 14% had elevated hs-CRP, and 20% had slightly
      elevated morning cortisol levels. We found that low coworker support affects more
      men than women, and that there are positive correlations between depression and
      serum cortisol both in men and in women, and also in the total group. There are
      no significant correlations in total group between depression and other
      inflamatory markers; only in women there are some positive correlations with
      fibrinogen and CRP. CONCLUSION: Professional stress is connected with
      inflammation and this could be a pathway through cardiovascular disease. There
      are some gender differences in stress perception which should be taken into
      account.

PMID- 21180243
TI  - The plasma homocysteine concentrations and prior myocardial infarction.
AB  - Elevated plasma homocysteine levels are associated with increased risk of
      vascular disease and with a relationship between homocysteine values and disease
      severity. Several studies have shown that the high plasma level of homocysteine
      is an important predictor for risk of cardiovascular events. We analysed the
      relationship between homocysteine concentrations and other risk factors into CAD
      progression in patients of prior myocardial infarction. METHODS: We performed a
      study including 208 patients (100 men and 108 women) divided into two groups: 104
      patients with prior myocardial infarction and 104 without coronary artery
      disease. RESULTS: The patients with prior myocardial infarction had higher mean
      values of plasma homocysteine than the controls (18.98 +/- 4.72 vs. 14.09 +/-
      3.32 micromol/L, p < or = .001). Multivariate analysis after the adjustment for
      age, gender and cardiovascular risk factors has identified homocysteine over 15
      micromol/L as significant and independent cardiovascular risk factors (odds ratio
      2.05; 95% CI 1.56-2.54). The correspondent Receiver Operator Curve shape
      suggested a good reliability in diagnosis of coronary artery disease for
      homocysteine (under curve area = 0.671, p < or = 001). CONCLUSION: Our results
      showed a positive correlation between plasma homocysteine levels and severity of
      coronary lesions (r = 0.765, p < .005). We suggest the use of homocysteine in
      clinical practice as marker of cardiovascular risk assessment.

PMID- 21180244
TI  - Chronic myeloid leukemia--from the National to the European Registry--limited
      experience of a single center.
AB  - Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder in which the
      diagnosis is confirmed by detection of a genetic marker: Philadelphia (Ph)
      chromosome in almost 90% of cases. Some of Ph1 negative patients, nevertheless,
      test positive for the abnormal gene, or the abnormal protein associated with this
      chromosome, when more sensitive studies, such as PCR or FISH are used and
      nowadays the diagnosis of CML is based, not only on cytogenetic, but also on
      molecular analysis. The better understanding of the CML biology provided by the
      latest researches requires a deeper knowledge about the epidemiologic data in
      each geographic area, so the compiling of a National and/or European Registry for
      CML patients, that represents one of the aims of this study, became a stringent
      matter in our days; it can offer valuable data concerning the real incidence of
      this disease in Romania and can provide the basics for establishing long-term
      budgetary strategies.

PMID- 21180245
TI  - Polymorphism of catalase gene promoter in Romanian patients with diabetic kidney
      disease and type 1 diabetes.
AB  - Hyperglycaemia leads to ROS (Reactive oxygen species) generation, affecting the
      cells that cannot decrease glucose uptake such as: glomerular epithelial cells,
      mesangial cells and proximal tubule cells. ROS excess seems to activate important
      pathogenic pathways of development of diabetic nephropathy. The decrease of CAT
      activity, one of the most important antioxidant enzymes, following to some
      genetic defects, may be a risk factor for diabetic nephropathy. The purpose of
      this study is to investigate the association of 21A/T (rs7943316) polymorphism of
      CAT gene with advanced diabetic nephropathy in patients with type 1 diabetes in
      Romania. There have been studied 238 patients with T1D (type 1 diabetes), divided
      into the group with diabetic nephropathy (DN) (106 patients) and the group
      without renal affectation (132 patients). The genotyping has been made by using
      PCR-RFLP technique. The analysis of association has been made by using DeFinetti
      programme. The value considered significant has been p < 0.05. There has been a
      deviation from Hardy-Weinberg equilibrium in the group with diabetic nephropathy
      (p = 0.019), the equilibrium being preserved by the control group (p = 0.771). T
      allele does not confer a risk for advanced diabetic nephropathy (ORT = 0.757, 95%
      C.I. = 0.405-1.414; P = 0.381), the result being statistically insignificant even
      taking into consideration the risk allele A (ORA = 0.793, 95% C.I. = 0.465-1.350;
      P = 0.392). The results remain concordant too after applying the Cochran 
      Armitage test. Our data do not suggest an effect of 21A/T (rs7943316)
      polymorphism in the susceptibility for diabetic nephropathy in Romanian patients
      with type 1 diabetes. Further studies are necessary in order to demonstrate or
      exclude the role of CAT gene in diabetic nephropathy in patients with type 1
      diabetes.

PMID- 21180246
TI  - Regression of precancerous epithelial alteration in patients with Helicobacter
      pylori chronic gastritis.
AB  - As a Group 1 carcinogen for gastric cancer, Helicobacter pylori (H. pylori) was
      involved in many studies and researches focused on physiopathology and
      morphopathologic changes induced by this bacterium. The study included 3069
      gastric endoscopies performed between January 2005 and December 2009 in
      "Colentina" Clinical Hospital. During upper endoscopy biopsies from antro-pyloric
      and corporeo-fundic region were collected. Histopathologic diagnosis of these
      biopsies was made using Sydney criteria. The patients were divided in two groups,
      based on the presence or absence of H. pylori: group A included 1414 H. pylori
      positive patients and group B included 1653 H. pylori negative patients. We
      evaluated several histopathological parameters, correlating the degree of
      inflammation, atrophy, metaplasia, regenerative hyperplasia and dysplasia with
      the presence of H. pylori infection. Our study identifies an overall tendency
      towards regression of premalignant lesions of gastric epithelium (regenerative
      epithelial hyperplasia, atrophy and intestinal metaplasia) after H. pylori
      eradication, as well an increasing number of patients diagnosed with early
      gastric cancer, thus consolidating the results of studies who foretell the
      significant decrease of gastric cancer mortality. These lesions are present years
      before becoming clinically manifest, and consequently treatable. In respect of
      carcinogenic mechanisms, some of our results confirm the carcinogenic cascade
      triggered by the H. pylori infection, as it was proposed by Correa et al. in
      1975. However, we obtained data leading to the idea that the "precursor lesions"
      could appear (and subsequently histopathologically evaluated) independent one to
      the other, through other steps then Correa's model.

PMID- 21180247
TI  - Plasma myeloperoxidase levels in patients with acute ischemic stroke.
AB  - Myeloperoxidase (MPO) is a glycoprotein released by activated polymorphonuclear
      neutrophils, which takes part in the defence of the organism through production
      of hypochlorous acid (HOCl), a potent oxidant. MPO has a role in pathogenesis of
      atherosclerosis. The aim of the study was to evaluate the time course of MPO
      plasma levels in the early stage of ischemic stroke. The study included 78
      patients with acute ischemic stroke, 46 females and 32 males, mean age 74.3 +/-
      6.8 years. Blood samples for MPO measurement were taken within 24 hours after the
      onset of ischemic stroke. Seventy-two patients served as matched controls 43
      females and 29 males, mean age 71.3 +/- 6.4 years. MPO was measured in plasma
      using the Abbott Architect platform (Abbott Diagnostics Inc., Abbott Parck IL).
      Comparisons between patients and controls and patients group were expressed as
      relative risk with its 95% confidence interval (RR [95% CI]), where a lower limit
      > 1.0 was considered significant. All p values were determined by Fischer's exact
      test. A value of p < 0.05 was considered statistically significant. Mean plasma
      MPO level was in patients with acute ischemic stroke 583 +/- 48 pmol/L. Seventy
      one patients out of seventy-eight patients with ischemic stroke presented mean
      plasma MPO levels greater than the upper of normal (425 +/- 36 pmol/L, p <
      0.0001, (RR 8.188, [95% CI 4.038 to 16.600]). Twelve controls presented mean
      plasma MPO level greater than the upper of normal. In conclusion, plasma MPO
      levels were statistically significantly higher in patients after ischemic stroke
      as compared to controls. MPO has been associated with acute ischemic stroke but
      its direct role in its pathogenesis has not been established. MPO could be
      proposed as a potential prognostic marker of such lesions rather than a marker of
      diagnosis. MPO is a new biomarker and a possible future therapeutic target.

PMID- 21180248
TI  - An adult case with onset of celiac disease during chronic hepatitis C antiviral
      treatment.
AB  - We present the case of young women who developed celiac disease during the
      treatment for chronic hepatitis C. Celiac disease is now considered to be an
      immune disorder that is triggered by an environmental agent in genetically
      predisposed persons. Many studies have shown that the total prevalence of gluten
      sensitive-enteropathy has increased over last decades, and advances in
      serological screening leads to the idea that there are more celiac disease cases
      that are asymptomatic and undiagnosed. Actually, pegylated interferonum (IFN) in
      combination with ribavirine provides the most effective treatment for patient
      with chronic hepatitis C. However, interferon and ribavirin therapy are
      associated with induction or exacerbation of preexistent autoimmune disorders.

PMID- 21180249
TI  - Iowa collaborative achieves improvement across the board.
AB  - Participants learn from each other, sharing successes and failures. Founders of
      collaborative embrace public reporting. Initiatives have different levels of
      engagement.

PMID- 21180250
TI  - Readmission rates for HF reduced by 30%.
AB  - Continuity of care a critical consideration. Advanced learning assessment
      conducted within 24 hours of admission. "Teach back" method employed with
      patients, family members.

PMID- 21180251
TI  - Where do EDs remain challenged?
AB  - Among those standards The Joint Commission reports offer the most difficult
      compliance challenges for hospitals, the three that have the greatest impact on
      EDs involve complete lab records, complete and accurate patient records, and
      egress. Install an electronic medical record, and verify that results have been
      reviewed. If you use a paper system, ensure that all final printed results are
      filed in the paper record. Involve clinicians who understand the standards in the
      selection of equipment.

PMID- 21180252
TI  - Medication reconciliation: another change planned.

PMID- 21180253
TI  - Actual legal risks if you did it but didn't document.

PMID- 21180254
TI  - Effects of retinoic acid and hydrogen peroxide on sterol regulatory element
      binding protein-1a activation during adipogenic differentiation of 3T3-L1 cells.
AB  - Both retinoic acid (RA) and oxidative stress (H2O2) increased transcription and
      cleavage of membrane-bound sterol regulatory element-binding protein (SREBP)-1,
      leading to enhanced transcription of fatty acid synthase (FAS) in hepatoma cells.
      On the other hand, RA and H2O2 decreased and increased lipogenesis in adipocytes,
      respectively, although roles of SREBP-1 activation in these effects remain to be
      elucidated. To elucidate its involvement, we examined the activation of SREBP-la,
      expression of FAS genes and lipid accumulation in 3T3-L1 cells in the presence of
      RA and/or H2O2. RA (1 microM) treatment suppressed expression of SREBP-1a and FAS
      genes and lipid accumulation. H2O2 (2 microM) treatment induced increased
      cleavage of SREBP-1a, without affecting amounts of SREBP-1a mRNA and precursor
      protein, and enhanced expression of FAS gene and lipid accumulation. Increased
      cleavage of SREBP-1a by H2O2 was also observed even in the presence of RA. These
      results suggest that H2O2, enhances a cleavage of SREBP-1a precursor protein,
      which independently occurs with the RA suppression of SREBP-1a gene expression,
      and that RA itself has no role in the SREBP-1a activation in adipocytes.

PMID- 21180255
TI  - Reduced transcript levels of the heat shock protein 70 gene in diminazene
      aceturate-resistant Babesia gibsoni variants under low concentrations of
      diminazene aceturate.
AB  - In our previous report, we developed a diminazene aceturate (DA)-resistant
      Babesia gibsoni strain that was maintained in culture with 200 ng/ml DA. While
      developing this strain, we also obtained DA-resistant B. gibsoni variants, which
      were maintained in culture with DA from 1 to 175 ng/ml for more than 8 weeks.
      Because heat shock protein 70 (Hsp70) seems to play important roles in adaptation
      to a stress environment in protozoan parasites, in the present study, we examined
      the copy number of B. gibsoni Hsp70 (BgHsp70) transcripts of those DA-resistant
      variants using quantitative real-time reverse transcription-polymerase chain
      reaction. We found that when wild-type B. gibsoni was exposed to 1 ng/ml DA, the
      level of BgHsp70 transcripts was decreased at day 14. The copy number of BgHsp70
      transcripts in the DA-resistant variant cultured with 1 ng/ml DA was
      significantly lower than in wild-type B. gibsoni, while those in DA-resistant
      variants increased with escalating doses of DA from 1 to 75 ng/ml, although they
      were lower than in wild-type B. gibsoni. However, those in DA-resistant variants
      cultured with >125 ng/ml DA were almost the same as wild-type B. gibsoni. These
      results indicated that the transcript levels of the BgHsp70 gene might be reduced
      when the parasites are exposed to a low concentration of DA, and then might
      recover to the normal level after achieving resistance against DA. We expect that
      further study of the function of BgHsp70 will elucidate the mechanism of drug
      resistance against DA in B. gibsoni.

PMID- 21180256
TI  - Dermal melanocytoma-acanthoma in an adult mixed breed dog.
AB  - A cutaneous melanocytoma-acanthoma was diagnosed in a 7-year-old intact female
      mixed breed dog. Grossly, this tumor was a solitary and darkly pigmented nodule
      located in the face. Histologically, the lesions consisted of melanocytic and
      epithelial tumor cells. The melanocytic component consisted predominantly of
      large round-to-polygonal and heavily pigmented melanocytic cells arranged in
      nests and clusters. These melanocytes were positive for S-100 and vimentin. The
      epithelial component was composed of multiple small horn cysts with concentric
      keratin within the cyst lumina and was positive for cytokeratin. Atypism was not
      observed in both components. Since this tumor has previously been reported in
      only two dogs, this report adds to the data that will help determing
      predilections of age, breed, sex and site.

PMID- 21180257
TI  - Effects of feeding buffering mineral mixture on subacute rumen acidosis and some
      production traits in dairy cows.
AB  - This trial was designed in order to evaluate the incidence of subacute rumen
      acidosis (SARA) during early lactation and to investigate the possibilities for
      its prevention by use of a buffering mineral mixture. On the beginning of the
      trial it was found that the pH value of rumen fluid in 4 animals was lower than
      normal (pH < 6.0) and that 20% of animals have had SARA. The control and the
      experimental group of cows were fed the same meal with exception of concentrated
      feed which in the experimental group contained the mineral mix with buffering
      activity in amount of 1%. Continuous addition of buffering mineral mixture in the
      amount of 1% in concentrated feed for early lactation cows successfully prevents
      SARA formation and leads to increased milk production, as well as increased milk
      fat and protein content.

PMID- 21180258
TI  - Inactivation strategy for pseudorabies virus in milk for production of
      biopharmaceuticals.
AB  - By selecting pseudorabies virus (PrV) as a model virus, this study assessed the
      feasibility of applying viral inactivation strategies to manufacturing medicinal
      products from the milk of transgenic sows. The efficacy of heat, acidic/alkaline
      and detergent treatments was also evaluated with respect to their ability to
      inactivate PrV in milk samples. Experimental results indicate that PrV was
      inactivated obviously at least 7.125 log10 for 30 min at 60 degrees C. At
      alkaline values of pH 10 and acidic value of pH 4, PrV infectivity was reduced to
      3.625 log10 and exceeded 5 log10, respectively. Moreover, PrV virus was
      inactivated efficiently (> 3.875 log10) by using 0.25-1% of Triton X-100
      treatment and without a loss of biological activity of the recombinant human
      coagulation factor IX (rhFIX). RESULTS: of this study demonstrate the
      effectiveness of the proposed detergent inactivation method for PrV inactivation
      of rhFIX production from transgenic products, especially in milk materials.

PMID- 21180259
TI  - Effects of estrogen replacement therapy on vascular endothelial growth factor
      expression in choroidal and retinal vasculature.
AB  - PURPOSE: To investigate the effects of estrogen replacement therapy (ERT) on
      vascular endothelial growth factor (VEGF) expression in choroidal and retinal
      vasculature in experimental rat model. METHODS: Forty female Wistar rats were
      randomized in 4 groups in the study. Subcutaneous ERT (17beta-estradiol, 10
      microg/kg/day) was administered for three months to first group without
      ovariectomy and to second group with ovariectomy. Rats in third group had only
      ovariectomy and fourth group had sham operation. At the end of the third month,
      all rats were sacrificed in estrous cycles determined by vaginal smear test and
      their right eyes were enucleated. Enucleated eyes were analyzed by
      immunohistochemical method for expression of VEGF. RESULTS: Only ovariectomy
      (group 3) in rats did not change VEGF expression than the sham operated (group 4)
      rats. However, there was more VEGF expression in groups receiving ERT than the
      group 3 and 4, but increased VEGF expression was statistically significant in
      group 1 in comparison to group 3, and 4 in both, choroidal and retinal
      vasculature. CONCLUSION: It was shown that ERT increases VEGF expression in
      choroidal and retinal vasculature, in particular in non-ovariectomized rats. Our
      findings suggest that ERT may be a risk factor for choroidal and retinal
      angiogenesis. Further studies are needed to evaluate the risks or benefits of
      exogenous estrogen supplementation for the choroidal and retinal angiogenesis in
      women (Fig. 2, Ref. 25).

PMID- 21180260
TI  - The oxidative by-product, hydroxyl radical, damaged immunoglobulin-G in patients
      with non-insulin dependent diabetes mellitus.
AB  - BACKGROUND AND OBJECTIVE: Free radical-mediated oxidative damage and consequent
      protein modifications are important mediators of cell toxicity and disease
      pathogenesis. Earlier investigations from our laboratory revealed an increased
      oxidative damage in diabetes patients and hydroxyl radicals (OH) caused an
      extensive damage to immunoglobulin G (IgG) and oxidatively modified IgG was found
      to be highly immunogenic in rabbits. Here, for the first time, we evaluated the
      role of hydroxyl radical-damaged IgG (OH-IgG) in non insulin dependent (Type 2)
      diabetes patients. METHODS: IgG was isolated from normal human serum by affinity
      chromatography and modified by hydroxyl radicals, generated by UV irradiation of
      hydrogen peroxide. Type 2 diabetes patients (n = 38) were accessed by direct
      binding and competitive inhibition ELISAs and the results were compared to
      healthy age and sex matched human subjects (n = 22). RESULTS: A high degree of
      specific binding by 31.6% of diabetes sera antibodies towards OH-IgG was
      observed, in comparison to its native analog (p < 0.01). Antibodies from normal
      human subjects showed negligible binding with either of antigens (p > 0.05).
      CONCLUSION: Our results suggest that hydroxyl radicals' modification of IgG
      causes structural perturbations, resulting in the generations of neo-epitopes,
      and making it a potential immunogen. The IgG modified with hydroxyl radicals may
      be one of the factors for the induction of circulating type 2 diabetes
      autoantibodies. The OH-IgG may proves one of the best markers to determine the
      oxidative stress in type 2 diabetes patients (Tab. 1, Fig. 4, Ref. 44).

PMID- 21180261
TI  - Circulating levels of VEGF family and their receptors in hepatocellular
      carcinoma.
AB  - To analyze the serum levels and prognostic significance of vascular endothelial
      growth factor (VEGF) family (VEGF-A, -C and -D) and their receptors (VEGFR-1 and 
      2) in patients with hepatocellular carcinoma. The serum levels of VEGF family
      members were measured in 56 control subjects and 68 patients with hepatocellular
      carcinoma using an enzyme-linked immunosorbent assay (ELISA). These measurements
      were correlated with clinic pathological features. The serum levels of VEGF-A and
      its receptor, VEGFR-1, were significantly higher in patients with hepatocellular
      carcinoma than in controls (p < 0.001). There was no significant difference in
      serum levels of VEGF-C and VEGFR-2 between patients and controls. VEGF-A levels
      were associated with advanced tumor stage and presence of metastases. VEGFR-1 was
      associated with metastases, advanced overall stage, tumor differentiation. VEGFR
      2 levels were associated with poor tumor differentiation. Serum VEGF levels are
      significantly in the same cohort of patients with variable clinic pathological
      features and prognostic values. The measurement of VEGF-A and its VEGFR-1 levels
      in sera may reflect the development of tumor, metastasis and angiogenesis (Tab.
      2, Ref. 20).

PMID- 21180262
TI  - Time course of nontyphoid salmonellosis in Slovakia 1957-2008.
AB  - AIM: To test in time salmonellosis data the hypothesis respecting the Moon
      gravity. METHODS: Daily numbers of admissions at Clinic of Infectology 2005-2006
      were processed on significance level alpha = 0.05, after finding out their non
      Poisson distribution, by cosinor regression in relation to the cycle new moon-
      full moon--new moon, lasting in average 29.53 days. In yearly incidence of this
      disease in Slovakia 1957-2008, presence of 18.6-year periodicity, connected with
      nutation of Moon axis, was tested. RESULTS: In agreement with our results 20
      years ago, statistically significant 14.76-day rhythm was revealed,with
      pronounced swings downwards and upwards near full and new moon again. It is
      matching the cycling of lunar gravity. In the yearly data, statistically
      significant 18.6-yearly period, roughly reciprocal against the lunisolar
      gravitation, is apparent. It has been confirmed by cross-linear regression.
      CONCLUSIONS: This study may testify to a causal relationship between the gravity
      and the occurrence of salmonellosis. The 18.6-years' cycling could explain the
      allegedly global phenomenon--steep decrease of incidence since about 2000.
      Nevertheless, it succeeds to an equally long and steep increase since 1990,
      corresponding so far to the found periodicity without proving a supposed new
      trend.The next years will decide whether the decrease will continue in the sense
      of this trend towards eradication of this disease or repeated increase will occur
      in the frame of continuing periodicity. Our findings are indirectly supported by
      the laboratory documentation of increased virulence of Salmonella in
      microgravity, published from NASA laboratories 10 years ago. Its practical
      exploitation for protecting the health of crew of cosmic flights is expected
      (Fig. 4, Ref. 15).

PMID- 21180263
TI  - The effects of E-cadherin and bcl-2 on prognosis in patients with breast cancer.
AB  - BACKGROUND: Breast cancer is the most common malignancy in women. Axillary lymph
      node involvement and tumor size are the most significant prognostic factors in
      breast cancer. However, more factors are needed for evaluating the prognosis and
      individualizing the treatment in these patients. Intracellular adhesion molecule
      E-cadherin, antiapopitotic protein bcl-2, and p53 might have predictive and
      prognostic properties in breast cancer. OBJECTIVE: We have investigated the
      effects of E-cadherin, bcl-2, and p53 on disease free survival and overall
      survival in patients with breast cancer. METHODS: Positivity of aforementioned
      genes was detected with immunohistochemistry staining. Seventy-six women patients
      with invasive ductal and lobular breast cancer who had received adjuvant therapy
      were included in the study. RESULTS: Bcl-2, E-cadherin, and p53 expression in
      tumor tissue specimens were found in 26.31%, 35.52%, and 9.21%, respectively.
      Mean duration of follow-up was 93.58 +/- 3.40 months. In multivariate analyses,
      axillary lymph node presence and C-erb-B2 overexpression were a strong negative
      prognostic factor of disease free survival and overall survival. E-cadherin and
      bcl-2 failed to have an effect on disease free survival and overall survival in
      our study. In addition, p53 overexpression was determined in a limited number of
      patients. CONCLUSIONS: The results of this study showed that E-cadherin, bcl-2,
      and p53 did not have any significant prognostic value for our patients. In order
      to arrive at a decision, we need studies, which include more patients and long
      follow-up periods (Tab. 2, Fig. 2, Ref. 24).

PMID- 21180264
TI  - An evaluation of the tuberculin skin test for anti TNF alpha prophylaxis in
      patients with ankylosing spondylitis and rheumatoid arthritis.
AB  - AIM: The tuberculin skin test (TST) has recently been proposed as a screening
      procedure for latent TB prior to anti-tumor necrosis factor (TNF) alpha therapy.
      Our aim was to evaluate TST levels in patients receiving anti TNF alpha due to
      ankylosing spondylitis (AS) and rheumatoid arthritis (RA). MATERIALS AND METHODS:
      73 AS patients (52 male, 21 female) and 33 RA patients (11 male, 22 female) were
      enrolled in the study. Patients' clinical and demographic characteristics were
      recorded. Average age +/- standard deviation was 38.8 +/- 7.2 years for AS and
      40.7 +/- 13 for RA. Median number of immunosuppressive agents used was 1 (min
      max) (0-2) in AS and 2 (2-3) in RA. To determine the activity of the disease,
      BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) was measured in AS
      patients, and DAS 28 (Disease Activity Index) was used in RA patients. TST was
      performed using the Mantoux method in all patients. RESULTS: Mean BASDAI was 5.1
      +/- 0.8 in AS, and DAS 28 score in RA was 5.7 +/- 0.5. Both, AS and RA patients
      had active disease. TST values were higher in AS than in RA patients. TST values
      were 11.5 +/- 6.5 mm in AS patients, compared to 7.0 +/- 6.4 mm in RA patients. A
      positive correlation between disease duration and TST was determined in AS
      patients. There was also a weak correlation in RA patients between
      immunosuppressive use and TST (r = 0.37, p = 0.032). No correlation was
      determined with disease activation in AS or RA patients. CONCLUSION: This is the
      first study to evaluate the correlation between the use of multiple
      immunosuppressive agents and TST. We determined that TST is correlated with
      disease duration in AS and with the use of multiple immunosuppressive agents in
      RA (Tab. 3, Ref. 21).

PMID- 21180265
TI  - Pralidoxime--the gold standard of acetylcholinesterase reactivators--reactivation
      in vitro efficacy.
AB  - OBJECTIVE: In this work, we aim to summarize the universality of this compound,
      its reactivation potential when different cholinesterase inhibitors are used.
      BACKGROUND: Pralidoxime is considered as a gold standard of acetylcholinesterase
      reactivators--antidotes used in case of nerve agent poisonings. It has been
      commercially available for many years. However, several studies deem this oxime
      an old-fashion antidote. METHODS: Pralidoxime was synthesized at our department.
      The reactivating efficacy was tested on 10% (w/v) rat brain homogenate that had
      been incubated with appropriate inhibitor for 30 minutes to reach 96% inhibition
      of AChE. Then, pralidoxime was added for 10 minutes. Measurements were performed
      at 25 degrees C, pH 8, and 10(-3) and 10(-5) M concentrations of AChE
      reactivators. The activities of brain AChE were measured by a potentiostatic
      method. RESULTS: No sufficient reactivation was achieved at the concentration of
      10(-5) M, which is a concentration that can be reached after administration of
      therapeutic doses. At a higher dose (10(-3) M), pralidoxime reactivated AChE
      inhibited by paraoxon, chlorpyrifos, Russian VX, VX and sarin. CONCLUSION: From
      the obtained results, it is clear that pralidoxime seems to be a poor reactivator
      of AChE inhibited by organophosphorous AChE inhibitors and thus cannot be labeled
      as a universal reactivator (Tab. 1, Fig. 3, Ref. 31).

PMID- 21180266
TI  - The relationship between histomorphological characteristics and Ki-67
      proliferation index in meningiomas.
AB  - OBJECTIVES: This study had two aims. The first was to use the Ki 67 proliferation
      index (Ki-67 PI) to study the relationship between the proliferation potential
      and histopathological features such as mitosis, necrosis, loss of architecture,
      small cell change, hypercellularity, pleomorphism, brain invasion, dura invasion,
      bone invasion, and histological grade. The second aim was to compare primary and
      recurrent meningioma with respect to morphological characteristics and Ki-67 PI
      values. BACKGROUND: Meningiomas are tumors whose histological features do not
      predict their biological behavior. Despite their slow growth and even after total
      resection, recurrence may occur METHODS: A total of 245 meningioma cases in whom
      Ki-67 PI was studied were included in the study. The cases were assessed with
      respect to 10 morphological characteristics, and a possible significant
      relationship between these and Ki 67 PI was statistically tested. RESULTS: We
      found a statistically significant relationship between Ki-67 PI and mitotic
      activity, necrosis, loss of architecture, small cell change, brain invasion. In
      contrast to brain invasion, no significant relationship was present between dura
      or bone invasion and Ki-67 PI. We identified asignificant increase in the
      histological grade, mitotic activity and Ki-67 PI value of recurrent tumors, as
      compared to primary ones CONCLUSION: Ki-67 PI values overlap in different grades.
      This overlapping might be due to the heterogeneity of biological activity within
      the tumor tissue (Tab. 2, Fig. 7, Ref. 21).

PMID- 21180267
TI  - Digital mammography--a new trend in breast carcinoma diagnostics.
AB  - OBJECTIVES: To determine the advantages of digital mammography in early detection
      of breast carcinoma. BACKGROUND: A new full field digital mammograph was
      installed at St. Elisabeth Oncology Institute in Bratislava 13 months ago. During
      this period we gained experience using this equipment and compared it to the
      foreign countries. METHOD: Comparison of digital and conventional mammography.
      RESULTS: During the period of 13 months 11 799 patients were examined, 5664 with
      conventional and 6135 with digital mammograph. We diagnosed 98 cases of breast
      carcinoma (1.6%, p = 0.67) with digital mammography, out of which 17 (17.3%, p =
      0.47) were in stage of carcinoma in situ. Using a conventional mammography 68
      cases (1.2%) of breast carcinoma were diagnosed, 9 cases (13.2%) as carcinoma in
      situ. Recall rate differed significantly--for digital mammography it reached 6.9%
      in comparison to conventional mammography where the recall rate was 9.5%, p <
      0.05. Digital mammography seems to be more sensitive in the detection of early
      stages of breast carcinoma as well as it is selectively advantageous in women
      with dense breast, perimenopausal women, patients with hormonal replacement
      therapy. CONCLUSION: Digital mammography is the state-of-the-art method of the
      early stages breast carcinoma detection especially when enhanced with a CAD
      system. A considerable contribution of digital mammography will find its use in
      interventional mammodiagnostic methods (Tab. 1, Fig.5, Ref. 7).

PMID- 21180268
TI  - Retinopathy of prematurity--epidemics, incidence, prevalence, blindness.
AB  - Currently, there are enough financial resources in industrial most developed
      countries to provide quality health care to the risk population of premature
      children. Neonatological units are equipped with state-of-the-art technological
      background, and highly qualified personnel are employed at the units. This as
      well allows providing optimum care of extremely immature newborns. ROP prevalence
      in these countries reaches approximately 5-8%. Today, a boom of surviving
      premature newborns can be seen in countries with medium-developed economy.
      Nevertheless, limited financing resources do not allow for standard high-level
      care. In such countries, the prevalence reaches up to 30%. In this respect, the
      "third ROP epidemic" is mentioned. Birth weight and gestational age parameters
      achieve significantly lower values in ROP-infants than in those not affected by
      the disease. Higher number of surviving immature newborns correlates with an
      increased risk of advanced ROP stages occurrence, while the frequency and degree
      of the disease are of inverse nature to the gestational age and birth weight
      (Tab. 1, Ref. 39).

PMID- 21180269
TI  - Thrombelastography during an acute normovolemic hemodilution in patient
      undergoing radical retropubic prostatectomy.
AB  - The aim of our study was to monitor a patient undergoing radical prostatectomy
      (RP) with an extraordinary large blood loss of 3600 ml. The perioperative
      bleeding was minimalized through an acute normovolemic hemodilution (ANH). During
      the procedure we monitored the patient's hemocoagulation profile. ANH is one of
      the possibilities for practical and pragmatic hemotherapy. It is a safe and
      effective method when facing massive blood loss or when it is necessary to
      temporarily replace or substitute the blood with a fluid during the operation
      (through a transfusion of allogeneic blood); and the patient benefits from the
      procedure. We argue that during ANH, the hypercoagulatory state appears in the
      patient--and even during the introduction of a combined solution of both
      crystalloids and colloids. In fact, during ANH it should not be recommended to
      provide a substitute for the patient's blood using only a single crystalloid
      solution alone (Tab. 2, Ref. 16).

PMID- 21180270
TI  - Relation between personality dimensions and depressive symptoms in patients on
      hemodialysis.
AB  - The aim of the study was to investigate the relationship between the presence of
      depressive symptoms and certain dimensions of personality in hemodialysis
      patients. The study included 93 subjects of both sexes, aged 24-78 years. All
      subjects were undergoing hemodialysis treatment for terminal stage renal
      insufficiency. The presence of depressive symptoms was operationally defined by
      the factor scores for the first principal components on the Beck Depression
      Inventory. Five personality dimensions were operationally defined by the factor
      scores for the first principal components on each of the five scales of the Big
      Five Inventory. The following dimensions of personality were assessed:
      neuroticism, extraversion, openness, agreeableness, and conscientiousness. The
      relationship between the five dimensions of personality and the presence of
      depressive symptoms was analyzed by the multiple regression analysis. The results
      showed that personality dimensions are significantly connected with the
      occurrence of depressive symptoms (R = 0.729; R2 = 0.532; F (5,87) = 19.822; p =
      0.000). Two partial predictors were significantly connected with depressive
      symptoms. They were higher degree of neuroticism (beta = 0.082, p = 0.000) and a
      lower degree of openness (beta = -0.235, p = 0.016).

PMID- 21180271
TI  - Non-atherosclerotic arteriopathy as the cause of ischemic stroke among young
      adults.
AB  - The study comprised 100 ischemic stroke patients of both sexes aged 15-45 years
      who were treated at the Clinic of Neurology of the Clinical Center of Vojvodina
      in the period January 2001-September 2004. All study subjects were divided into
      three age groups: 15-25, 26-35 and 36-45 years. Sex, age and risk factors for
      cerebrovascular disease were determined in all patients. Diagnostic procedures
      applied in all patients included brain computed tomography and/or magnetic
      resonance imaging, routine laboratory tests, Doppler imaging of extra and
      endocranial blood vessels and coagulation tests. Contrast and/or transesophageal
      echocardiography, immunological blood assays, magnetic resonance angiography
      and/or computed tomography angiography and/or conventional angiography,
      thrombophilia markers, antiphospholipid antibodies and toxicological examination,
      etc. were performed in selected patients. Non-atherosclerotic arteriopathies were
      found in 8% of all study subjects, and were the most frequent cause of stroke in
      the age group 15-25. Carotid artery dissection was the most frequent diagnosis
      overall, found in 6% of all patients. Fibromuscular dysplasia and systemic
      vasculitis were diagnosed in one patient each. Moyamoya disease, Takayasu
      disease, infectious and isolated vasculitis of the CNS were not found in our
      patients.

PMID- 21180272
TI  - Clinical and pathological features of Riedel's thyroiditis.
AB  - OBJECTIVE: To evaluate the clinical and pathological features of Riedel's
      thyroiditis (RT), and current diagnostic and treatment methods for that disease.
      METHODS: Five RT cases identified by surgery and pathological examinations at
      Peking Union Medical College Hospital from 1985 to 2009 were analyzed and
      compared with the cases reported in the literature in terms of clinical and
      pathological features. Immunohistochemical staining of kappa and lambda light
      chains was carried out for RT tissues from all the five patients. RESULTS: All
      the five cases were females, aged 45-55 years. Elevation of serum thyroid
      autoantibodies was found in only one patient, who had longer disease duration
      than the others. Pathological examination revealed invasive fibrosclerosis of the
      thyroid follicles, thyroid capsule, and the surrounding tissues. In RT tissues,
      the number of cells containing lambda chains was a little higher than those
      containing kappa chains. CONCLUSIONS: RT is a rare disease which might be more
      common in middle-aged females than in other populations. Pathological features
      include the destruction of thyroid follicle, extension into surrounding tissues
      by inflammatory cells and fibrous tissues. Immunohistochemical staining of kappa
      and lambda chains could help diagnose RT.

PMID- 21180273
TI  - Diagnosis and treatment of infective endocarditis in chronic hemodialysis
      patients.
AB  - OBJECTIVE: To analyze the clinical features of hemodialysis patients complicated
      by infective endo carditis. METHODS: The clinical features of six such patients
      admitted to Peking Union Medical College Hospital during the year 1990 to 2009
      were analyzed. All of them were diagnosed based on Chinese Children Diagnostic
      Criteria for Infective Endocarditis. RESULTS: The average age of the six patients
      was 52.3 +/- 19.3 years old. Four were males. Vascular accesses at the onset of
      infective endocarditis were as follows: permanent catheters in three, temporary
      catheters in two, and arteriovenous fistula in one. Three were found with mitral
      valve involvement, two with aortic valve involvement, and one with both. Five
      vegetations were found by transthoracic echocardiography, and one by
      transesophageal echocardiography. Four had positive blood culture results. The
      catheters were all removed. Four of the patients were improved by antibiotics
      treatment, in which two were still on hemodialysis in the following 14-24 months
      and the other two were lost to follow-up. One patient received surgery, but died
      of heart failure after further hemodialysis for three months. One was well on
      maintenance hemodialysis for three months after surgery. CONCLUSIONS: Infective
      endocarditis should be suspected when hemodialysis patients suffer from long-term
      fever, for which prompt blood culture and transthoracic echocardiography
      confirmation could be performed. Transesophageal echocardiography could be
      considered even when transthoracic echocardiography produces negative findings.
      With catheters removed, full course of appropriate sensitive antibiotics and
      surgery if indicated could improve the outcome of chronic hemodialysis patients
      complicated by infective endocarditis.

PMID- 21180274
TI  - The St. George's Respiratory Questionnaire in lymphangioleiomyomatosis.
AB  - OBJECTIVE: To examine the correlation between the health-related quality of life
      measured by the St. George's Respiratory Questionnaire (SGRQ) and the commonly
      used physiological measures in lymphangioleiomyomatosis (LAM). METHODS: This
      study retrospectively analyzed the SGRQ scores and other measures (the Borg scale
      of breathlessness at rest, 6-minute walking distance, blood oxygen levels, and
      pulmonary function) of patients diagnosed and confirmed with LAM. Altogether 38
      patients between June 2007 and November 2009 were included. RESULTS: The mean
      values of the SGRQ three components (symptoms, activity, and impacts) and total
      scores in the LAM patients were 46.95 +/- 28.90, 58.47 +/- 25.41, 47.89 +/-
      29.66, and 51.11 +/- 26.35, respectively. The SGRQ total or component scores were
      correlated well with the Borg scale of breathlessness, 6-minute walking distance,
      partial pressure of oxygen in arterial blood, spirometry and diffusion capacity
      of lung. There were poor correlations between SGRQ score and residual volume or
      total lung capacity. In our preliminary observation, sirolimus improved the SGRQ
      total and three component scores and the Borg scale of breathlessness
      significantly after 101-200 days of treatment (n = 6). CONCLUSIONS: The SGRQ
      score in LAM is correlated well with physiological measures (Borg scale of
      breathlessness, 6-minute walking distance, blood oxygen levels, and pulmonary
      function tests). The SGRQ could therefore be recommended in baseline and follow
      up evaluation of patients with LAM. Treatment with sirolimus, an inhibitor of
      mammalian target of rapamycin, may improve the quality of life and patient's
      perception of breathlessness in LAM.

PMID- 21180275
TI  - Effects of acute normovolemic hemodilution on perioperative coagulation and
      fibrinolysis in elderly patients undergoing hepatic carcinectomy.
AB  - OBJECTIVE: To observe the effects of acute normovolemic hemodilution (ANH) on
      coagulation function and fibrinolysis in elderly patients undergoing hepatic
      carcinectomy. METHODS: Thirty elderly patients (aged 60-70 years) with liver
      cancer (American Society of Anesthesiologists physical status I-II) scheduled for
      hepatic carcinectomy from February 2007 to February 2008 were randomly divided
      into ANH group (n = 15) and control group (n = 15). After tracheal intubation,
      patients in ANH group and control group were infused with 6% hydroxyethyl starch
      (HES) (130/0.4), and basic liquid containing 6% HES and routine Ringer's
      solution, respectively. In all the studied patients, blood samples were drawn at
      five different time points: before anesthesia induction (T1), 30 minutes after
      ANH (T2), 1 hour after start of operation (T3), immediately after operation (T4),
      and 24 hours after operation (T5). Then coagulation function, soluble fibrin
      monomer complex (SFMC), prothrombin fragment (F1+2), and platelet membrane
      glycoprotein (activated GPIIb/GPIIIa and P-selectin) were measured. RESULTS: The
      perioperative blood loss was not significantly different between the two groups
      (P > 0.05). The volume of allogeneic blood transfusion in ANH group was
      significantly smaller than that in control group (350.5 +/- 70.7 mL vs. 457.8 +/-
      181.3 mL, P < 0.01). Compared with the data of T1, prothrombin time (PT) and
      activated partial thromboplastin time in both groups prolonged significantly
      after T3 (P < 0.05), but still within normal range. There were no significant
      changes in thrombin time and D-dimer between the two groups and between different
      time points in each group (all P > 0.05). SFMC and F1 + 2 increased in both
      groups, but without statistical significance. P-selectin expression on the
      platelet surface of ANH group was significantly lowered at T2 and T3 compared
      with the level at T1 (P < 0.05). Compared with control group, P-selectin was
      significantly lower in ANH group at T2-T5 (all P < 0.05). CONCLUSIONS: In elderly
      patients undergoing resection of liver cancer, ANH may not hamper fibrinolysis
      and coagulation function. It could therefore be safe to largely reduce allogeneic
      blood transfusion.

PMID- 21180276
TI  - Ultrasonographic characteristics of intraductal papillary mucinous neoplasm of
      the pancreas.
AB  - OBJECTIVE: To analyze the clinical and ultrasonographic imaging features of
      intraductal papillary mucinous neoplasm (IPMN) of the pancreas. METHODS: Twelve
      patients with IPMN underwent surgery between May 2005 and December 2008,
      including 4 (33.3%) with adenoma and 8 (66.7%) with adenocarcinoma. IPMN was
      classified preoperatively into 3 types based on sonographic findings of different
      sites: main duct, branch duct, and combined type. All clinical presentations and
      ultrasonographic findings of those patients were reviewed and the correlation
      between ultrasonographic findings and histopathological results was analyzed.
      RESULTS: There were 9 men and 3 women with a mean age of 60.1 +/- 9.6 years
      (range, 32-73). Of all the 12 patients with IPMN, 9 (75.0%) had experienced some
      symptoms of epigastric discomfort and/or pain as well as backache; 7 cases were
      with medical history of acute pancreatitis, 5 cases with diabetes, 4 cases with
      elevated CA19-9, and 2 cases with steatorrhea. All lesions of IPMN have been
      revealed by transabdominal ultrasonography. The mean diameters of the lesions
      were 1.4 +/- 0.8 cm (range, 0.5-2.0) and 6.3 +/- 6.0 cm (range, 2.0-20.0) in
      adenomas and adenocarcinomas, respectively. And the mean diameters of the main
      duct in adenomas and adenocarcinomas were 1.0 +/- 0.8 cm and 1.6 +/- 1.0 cm,
      respectively. Among the 4 adnomas, 3 (75.0%) cases were classified as branch type
      based on sonographic findings, and 2 were demonstrated as mural nodules in which
      no color signals was detected. Among the 8 adenocarcinomas, 5 (62.5%) cases were
      classified as main duct type, and 3 (37.5%) as combined type. In 7 of the 8
      adenocarcinomas, mural nodules were detected within the dilated ducts or cysts of
      the lesions in which color flow signals were detected. CONCLUSIONS:
      Transabdominal ultrasonography can reveal the pancreatic cystic lesions of IPMN
      as well as dilated pancreatic ducts. Some characteristics should be noticed as
      suggesting the possibility of malignancy: clinical symptoms of pancreatic
      insufficiency, large tumor size, and mural nodules with color Doppler flow
      signals. Transabdominal ultrasonography could be a useful tool to help diagnose
      and make appropriate management of IPMN.

PMID- 21180277
TI  - Postoperative disc wedging in adolescent idiopathic thoracolumbar/lumbar
      scoliosis: a comparison of anterior and posterior approaches.
AB  - OBJECTIVE: To evaluate the different influences of anterior and posterior
      correction and fusion approaches upon disc wedging in adolescent idiopathic
      thoracolumbar/lumbar scoliosis. METHODS: The retrospective study was conducted
      with the medical records and radiographs of adolescent idiopathic
      thoracolumbar/lumbar scoliosis patients that underwent anterior (group A) or
      posterior (group B) correction and fusion surgery from December 1998 to May 2008.
      The correction of the main curve and changes of the disc wedging were analyzed.
      RESULTS: Fifty-three patients were included, 26 in group A and 27 in group B. The
      mean coronal Cobb angles of the main curve in group A and group B were
      significantly corrected after surgery (P < 0.05), with an average correction rate
      of 75.2% and 88.2%, respectively. Upon final follow-up, the coronal Cobb angles
      of the two groups were 18.90 +/- 11.1 degrees and 7.70 +/- 5.6 degrees,
      respectively, with an average correction loss of 6.8 degrees +/- 6.5 degrees and
      2.7 degrees +/- 3.3 degrees, respectively. The coronal Cobb angle after operation
      and at final follow-up, and the correction rate were significantly better in
      group B than those in group A (P < 0.05), while the coronal Cobb angle loss in
      group A was greater than that in group B (P < 0.05). The disc wedging before
      operation, after operation, and at final follow-up were 3.2 degrees +/- 3.0
      degrees, 5.7 degrees +/- 3.0 degrees, and 8.6 degrees +/- 4.4 degrees in group A,
      and 2.4 degrees +/- 3.2 degrees, 3.3 degrees +/- 3.4 degrees, and 3.7 degrees +/-
      3.6 degrees in group B, respectively. Postoperative disc wedging was
      significantly larger compared with preoperative measurements in group A (P <
      0.05), but not in group B (P > 0.05). The difference between disc wedging at
      final follow-up and that after surgery was significant in group A (P < 0.05), but
      not in group B (P > 0.05). Between the two groups, group A had larger disc angles
      after operation and at final follow-up (P < 0.05), and a greater loss of disc
      angle (P < 0.05). CONCLUSION: For adolescent idiopathic thoracolumbar/lumbar
      scoliosis, posterior approach using all pedicle screws might produce a better
      result in terms of disc wedging compared with anterior approach.

PMID- 21180278
TI  - mRNA expression of chemokine receptors on peripheral blood mononuclear cells and
      correlation with clinical features in systemic lupus erythematosus patients.
AB  - OBJECTIVE: To investigate the expressions of chemokine receptors and interleukin
      (IL) receptors on the peripheral blood mononuclear cells (PBMCs) from systemic
      lupus erythematosus (SLE) patients and their correlations with clinical features
      as well as SLE disease activity index (SLEDAI). METHODS: The mRNA expressions of
      chemokine receptors and IL receptors on PBMCs of 93 SLE patients and 30 healthy
      controls were detected by reverse transcription-polymerase chain reaction,
      including CCR2, CCR3, CCR4, CCR5, CCR6, CCR8, CXCR3, CXCRS, CX3CR1, XCR1, IL-4R,
      and IL-10R. The clinical features of SLE patients were recorded. The correlations
      of chemokine receptors and IL receptors mRNA expressions with clinical features
      as well as SLEDAI were assayed using linear regression analysis. RESULTS: The
      level of CCR5 mRNA in SLE patients (including active and inactive SLE) was
      significantly higher than that in healthy controls (P < 0.05), and there was no
      significant difference between active and inactive patients in this respect (P >
      0.05). CX3CR1 mRNA expression significantly increased from healthy control to
      inactive SLE to active SLE in sequence. The others (except for CCR8, CXCR3, and
      IL-10R) in active SLE patients were significantly higher than those in both
      inactive SLE patients and healthy controls (all P < 0.05). There were positive
      correlations between SLEDAI and CCR2 (r = 0.424, t = 4.313, P < 0.001), CCR3 (r =
      0.518, t = 5.410, P < 0.001), CCR4 (r = 0.376, t = 3.851, P < 0.001), CCR6 (r =
      0.457, t = 4.513, P < 0.001), CXCR5 (r = 0.455, t = 4.629, P < 0.001), CX3CR1 (r
      = 0.445, t = 4.523, P < 0.001), as well as XCR1 (r = 0.540, t = 5.445, P <
      0.001). And CCR5 mRNA expression level was positively correlated with IL-4R mRNA
      (r = 0.313, t = 2.353, P < 0.05). The patients with myositis and cutaneous
      vasculitis simultaneously showed lower levels of CCR5 and CX3CR1, and CCR5
      expression was negatively correlated with the scores of SLEDAI in SLE cases
      accompanied by photosensitivity (r = 0.426, t = -2.155, P < 0.05). CONCLUSION:
      Increased expressions of CCR5 and CX3CR1 on PBMCs may be indicators in clinical
      survey for SLE.

PMID- 21180279
TI  - Fatty acid synthase and hormone-sensitive lipase expression in liver are involved
      in zinc-alpha2-glycoprotein-induced body fat loss in obese mice.
AB  - OBJECTIVE: To explore the effects of zinc-alpha2-glycoprotein (ZAG) on body
      weight and body fat in high-fat-diet (HFD)-induced obesity in mice and the
      possible mechanism. METHODS: Thirty-six male mice were fed with standard food
      (SF) (n = 9) and HFD (n = 27), respectively. Five weeks later, 9 mice fed with
      HFD were subjected to ZAG expression plasmid DNA transfection by liposome
      transfection method, and another 9 mice to negative control plasmid transfection.
      Two weeks later, serum ZAG level in the mice was assayed by Western blot, and the
      effects of ZAG over-expression on body weight, body fat, serum biochemical
      indexes, and adipose tissue of obese mice were evaluated. The mRNA expressions of
      fatty acid synthase (FAS) and hormone-sensitive lipase (HSL) in liver tissue were
      determined by reverse transcription-polymerase chain reaction. RESULTS: Serum ZAG
      level significantly lowered in simple HFD-fed mice in comparison to SF-fed mice
      (0.51 +/- 0.10 AU vs. 0.75 +/- 0.07 AU, P < 0.01). Further statistical analysis
      demonstrated that ZAG level was negatively correlated with body weight (r = 
      0.56, P < 0.001), epididymal fat mass (r = -0.67, P < 0.001), percentage of
      epididymal fat (r = -0.65, P < 0.001), and increased weight (r = -0.57, P <
      0.001) in simple SF- and HFD-fed mice. ZAG over-expression in obese mice reduced
      body weight and the percentage of epididymal fat. Furthermore, FAS mRNA
      expression decreased (P < 0.01) and HSL mRNA expression increased (P < 0.001) in
      the liver in ZAG over-expressing mice. CONCLUSIONS: ZAG is closely related to
      obesity. Serum ZAG level is inversely correlated with body weight and percentage
      of body fat. The action of ZAG is associated with reduced FAS expression and
      increased HSL expression in the liver of obese mice.

PMID- 21180280
TI  - Effect of intracoronary infusion of bone marrow mononuclear cells or peripheral
      endothelial progenitor cells on myocardial ischemia-reperfusion injury in mini
      swine.
AB  - OBJECTIVE: To simulate and assess the clinical effect of intracoronary infusion
      of bone marrow mononuclear cells or peripheral endothelial progenitor cells on
      myocardial reperfusion injury in mini-swine model. METHODS: Twenty-three mini
      swine with myocardial reperfusion injury were used as designed in the study
      protocol. About (3.54 +/- 0.90) x 10(8) bone marrow mononuclear cells (MNC group,
      n = 9) or (1.16 +/- 1.07) x 10(7) endothelial progenitor cells (EPC group, n = 7)
      was infused into the affected coronary segment of the swine. The other mini-swine
      were infused with phosphate buffered saline as control (n = 7). Echocardiography
      and hemodynamic studies were performed before and 4 weeks after cell infusion.
      Myocardium infarction size was calculated. Stem cell differentiation was analyzed
      under a transmission electromicroscope. RESULTS: Left ventricular ejection
      fraction dropped by 0% in EPC group, 2% in MNC group, and 10% in the control
      group 4 weeks after cell infusion, respectively (P < 0.05). The systolic
      parameters increased in MNC and EPC groups but decreased in the control group.
      However, the diastolic parameters demonstrated no significant change in the three
      groups (P > 0.05). EPC decreased total infarction size more than MNC did (1.60 +/
      0.26 cm2 vs. 3.71 +/- 1.38 cm2, P < 0.05). Undermature endothelial cells and
      myocytes were found under transmission electromicroscope. CONCLUSIONS:
      Transplantation of either MNC or EPC may be beneficial to cardiac systolic
      function, but might not has obvious effect on diastolic function. Intracoronary
      infusion of EPC might be better than MNC in controlling infarction size. Both MNC
      and EPC may stimulate angiogenesis, inhibit fibrogenesis, and differentiate into
      myocardial cells.

PMID- 21180281
TI  - Cicatricial pemphigoid in accompany with rheumatoid arthritis: a case report.

PMID- 21180282
TI  - Non-Hodgkin's lymphoma primarily presenting with Fanconi syndrome and acute
      kidney injury.

PMID- 21180283
TI  - Laparoscopic partial splenectomy for giant hemangioma misdiagnosed as splenic
      cyst: a case report.

PMID- 21180284
TI  - Dental Protection Limited.

PMID- 21180285
TI  - A review of the diagnosis and management of the cracked tooth.
AB  - A cracked tooth is a common presentation in general dental practice. It may be
      difficult to diagnose, owing to the variations in the clinical presentation. The
      symptoms that result from a cracked tooth have given rise to the term Cracked
      Tooth Syndrome (CTS). This article reviews and discusses the clinical signs,
      symptoms and the management of CTS. An early diagnosis is important to relieve
      pain, restore function and improve the prognosis for the tooth. The prognosis can
      be unpredictable and this needs to be understood by patients before embarking on
      definitive treatment.

PMID- 21180286
TI  - Is orthodontics an option in the management of bimaxillary protrusion?
AB  - Successful orthodontic treatment is based on a clear perception by the clinician
      of a patient's facial preference and treatment needs. Bimaxillary protrusion is a
      normal facial trait seen in the Black population and the most acceptable
      bimaxillary facial profile in a sample of Black subjects was determined by Beukes
      et al in 2007. Variations from this ideal profile may require extractions as part
      of orthodontic treatment in order to attain the ideal. The objective of this
      study was to determine whether Black subjects with bimaxillary protrusion would
      want to change their facial profile to the ideal and at what financial cost. A
      sample of 586 school learners and 321 university students were presented with
      four silhouetted profiles of varying degrees of bimaxillary protrusion. One of
      the silhouette profiles represented the ideal and treatment procedures required
      to achieve this ideal were explained to the sample. They were then requested to
      answer a questionnaire that would assist in identifying their perception of their
      own profile and their desire to change their appearance. The ideal silhouette was
      confirmed to be the most attractive (91.51%) and the sample felt that any severe
      deviations from this ideal profile should be treated. The financial cost of
      treatment was found to be a concern, as more subjects (62.84%) would undergo the
      required treatment if it were free. Many subjects (43.55%) would be prepared to
      pay for the necessary treatment to achieve the ideal profile. Females were found
      to be more definite in their decision making, reflecting a greater awareness
      about their aesthetic appearance than their male counterparts. Findings from this
      study can serve as an essential tool to assist both orthodontists and
      maxillofacial surgeons in the treatment planning and management of Black patients
      with bimaxillary protrusion.

PMID- 21180287
TI  - Properties of a new mouthrinse for patients receiving radiation therapy.
AB  - INTRODUCTION: Patients receiving radiation therapy due to oral cancer develop
      complications such as hyposalivation, mucositis, oral infections, dental
      hypersensitivity and caries. Mouthrinses can alleviate some of these problems.
      AIMS AND OBJECTIVES: To investigate the in vitro antimicrobial properties and
      cytotoxicity of an experimental mouthrinse. METHODS: The mouthrinse contained 30%
      hexylene glycol (glycerine), 7% potassium nitrate and 0.025% sodium fluoride. The
      minimal inhibitory concentration (MIC) of these ingredients and the mixture was
      determined for C. albicans, S. aureus and S. mutans over 24 hours at different
      concentrations. The MICs of two commercial mouthrinses, Corsodyl and Plax, were
      also determined using the same organisms. All mouthrinses were then tested to
      determine the percentage kill over 1, 2, and 3 minutes. RESULTS: The MICs for
      hexylene glycol were 10%, 30% and 10% for C. albicans, S. aureus and S. mutons
      respectively. Potassium nitrate and sodium fluoride had no antimicrobial effects.
      The MIC of Corsodyl was 0.016 mg/ml for all the test organisms. The MIC for Plax
      varied from 0.0002 mg/ml to 0.001 mg/ml. The kill rates for all mouthrinses were
      acceptable, with no statistical differences between them. The experimental
      mouthrinse was not toxic to human oesophageal SCC cells after 1 minute exposure.
      At the time of the experiment, the costs of a similar quantity of the
      experimental mouthrinse, Corsodyl and Plax were R5.24, R30.00 and R10.00
      respectively. CONCLUSIONS: The experimental mouthrinse was cost-effective and
      proved to have an antimicrobial effect and could be used safely to alleviate oral
      infections, desensitize teeth, improve oral hygiene and control dental caries in
      cancer patients after radiation therapy.

PMID- 21180288
TI  - Root canal complications: 'the hypochlorite accident'.
AB  - Root canal treatment is performed routinely in dental practice, using sodium
      hypochlorite which serves as an effective irrigant. The literature reviewed shows
      that several complications following irrigation with sodium hypochlorite may
      occur, but few practitioners are aware of it and its management. Such
      complications include injury to skin, oral mucosa and eyes, damage to clothing,
      air emphysema, allergic reactions, and injection beyond the foramen. In this
      article, a case report of injection with sodium hypochlorite beyond the foramen
      is presented, together with a review of the recent literature regarding common
      manifestations and case histories. The literature shows no standard management of
      this condition, but symptomatic therapies are discussed. It is important to
      minimize the risk of sodium-hypochlorite-induced damage during root canal therapy
      by use of protective measures, appropriate instrumentation and techniques, and
      consider alternate irrigation solutions.

PMID- 21180289
TI  - Focal cemento-osseous dysplasia: review and a case report.
AB  - Focal cemento-osseous dysplasia is a benign fibro-osseous condition that can be
      seen in dentate and edentulous patients. It is an asymptomatic lesion and needs
      no treatment; however follow-up is essential due to the possibility that focal
      cemento-osseous dysplasia can progress to a condition called florid osseous
      dysplasia that involves multiple sites. A case report is presented here, along
      with a review of the differential diagnoses considered in order to reach a final
      diagnosis of focal cemento-osseous dysplasia.

PMID- 21180290
TI  - Oral cancer-associated paraneoplastic syndromes.
AB  - Paraneoplastic syndromes are cancer-associated endocrinological, haematological,
      dermatological or neurological disorders, which are directly related neither to
      the physical effects of the tumour mass, nor to invasion by the primary tumour,
      nor to metastasis of the tumour; nor are they associated either with the side
      effects of anticancer treatment or with any of the complications of cancer. These
      syndromes are brought about by the ectopic production of biological mediators by
      the malignant tumour cells, or by immunological responses to the malignancy.
      Certain cancers are typically associated with specific paraneoplastic disorders.
      Though uncommonly, oral carcinomata have reportedly been associated with
      paraneoplastic pemphigus, humoral hypercalcaemia of malignancy, syndrome of
      inappropriate antidiuretic hormone, and paraneoplastic leukocytosis syndrome.

PMID- 21180291
TI  - General practitioner's radiology case 87. Amelogenesis imperfecta.

PMID- 21180292
TI  - Emergency treatment.

PMID- 21180293
TI  - Oral medicine case book 31. Verrucous carcinoma.

PMID- 21180294
TI  - Dental ethics case 6. Stalled payment for ongoing orthodontic treatment-
      balancing responsibilities.
AB  - It is not always easy for an orthodontist to strike the right balance between a
      caring, supportive and patient-centered approach, and the need to make a living
      and to run a profitable business in order to achieve this. Striving to act
      ethically and professionally at all times will help find this elusive balance and
      ultimately it will be more rewarding and professionally satisfying. Especially
      when dealing with children whose lives may be dramatically affected by the
      interruption or cessation of treatment, orthodontists have a duty to reassure
      themselves about the financial stability of their contractual relationships with
      patients or parents. Having consistent financial policies and flexible payment
      options may assist in this regard. Even in the face of non-payment of fees,
      treatments that have begun must in some form continue if their cessation would
      compromise the best interests of patients.

PMID- 21180295
TI  - Students' guide to complete denture construction.

PMID- 21180296
TI  - Beta blockers and CVD protection; new frontriers.

PMID- 21180297
TI  - Beta blockers and CVD protection: new frontiers.

PMID- 21180298
TI  - Beta-blockers and heart failure.
AB  - The life-time risk of developing HF is about 20% (40% if hypertension present).
      With increasing longevity in the developed world the burden of HF
      (hospitalisation) is set to increase over the next 10-20 years. CAD and
      hypertension are the two main causes of HF; CAD (and obesity) in the case of
      systolic HF and hypertension in the case of diastolic HF (mainly in the elderly).
      BB have become the corner-stone (alongside ACE-inhibitors) in the treatment of
      systolic HF. Bisoprolol, metoprolol and carvedilol (on an ACE-inhibitor
      background) have reduced all-cause death by 34-5%. The presence of intrinsic
      sympathomemetic activity (xamoterol, bucindolol, nebivolol) diminishes efficacy
      in the treatment of systolic HF. First-line bisoprolol has proved "non-inferior"
      to first-line enalapril in reducing all-cause death and is probably superior in
      reducing sudden death. The main mode of action of BB in treating systolic HF is
      inhibition of chronic beta-1 stimulation-induced myocardial
      apoptosis/necrosis/inflammation. The combination of pure beta-1 blockade (low
      dose bisoprolol) and pure beta-2 blockade (clenbuterol) may prove invaluable in
      the treatment of end-stage systolic HF (thus avoiding cardiac transplantation).
      The appropriate treatment of diastolic HF has yet to be determined. Beta-blockade
      is effective in the prevention of HF i) in the post-MI period and ii) as first
      line agents in the treatment of young/middle-aged hypertension and as second-line
      agents (to first-line diuretics) in the treatment of elderly systolic
      hypertension. BB are highly effective in reversing LVH in young/middle-aged
      hypertensives (LVH pre-disposes to HF in young/middle-aged hypertension) and are
      (bisoprolol) at least as good as ACE-inhibitors. Choice of BB is important as
      benefit is not a class-effect. ISA (xamoterol, bucindolol, nebivolol) markedly
      diminishes efficacy. The choice is between bisoprolol, metoprolol succinate and
      carvedilol for optimal efficacy. Adverse reactions are associated, mainly, with
      beta-2 blockade and alpha-blockade. Thus non-selective (e.g. propranolol) or
      modestly beta-1 selective (e.g. metoprolol, atenolol) are associated with
      metabolic disturbance, bronchospasm, epinephrine/hypertensive interaction (with
      cigarette-smoking or insulin-induced hypoglycaemia), while the possession of
      alpha-blocking activity (e.g. carvedilol) is associated with dizziness and
      postural hypotension. The possession of beta-2 blockade, particularly if combined
      with alpha-blockade, is associated with an increased occurrence of sexual
      dysfunction. Lipophilic BB like propranolol and metoprolol appear in high
      concentrations in human brain tissue and are associated with side-effects such as
      insomnia, dreams and nightmares.

PMID- 21180299
TI  - The current state of beta blockers in hypertension therapy.
AB  - Beta adrenergic blockers have had a long history as frontline agents in
      hypertension therapy. They are the mainstay of treatment in ischemic heart
      disease, heart failure, high risk coronary artery disease and arrhythmias, as
      their importance in these compelling indications are well-established. However,
      the efficacy and relevance of beta blockers in the treatment of uncomplicated
      hypertension have been questioned because the traditional agents were deemed not
      atpar with drugs from other classes in terms of cardiovascular outcomes. Although
      atenolol and other traditional agent s have lost favor, the other cardioselective
      agents have been shown to be at least as efficacious in hypertension as the other
      classes of drugs. Their use in hypertension therapy should continue, especially
      in young and diabetic individuals where high sympathetic tone and high renin
      levels are the primary features. The newer-generation vasodilating beta blockers
      have favorable hemodynamic and metabolic properties, better side effect profile
      and improved efficacy in treating uncomplicated hypertension. With the advent of
      these new agents, the beta blocker class should remain as a viable first-line
      option in antihypertensive therapy.

PMID- 21180300
TI  - Perioperative beta-blockers: is it still useful?

PMID- 21180301
TI  - Beta blockers in cardiomyopathy: status report 2010.

PMID- 21180302
TI  - Beta blockers in coronary artery disease with and without hypertension.
AB  - Beta-adrenergic blockers (BB) were developed to treat angina. Trials of BB with
      myocardial infarction (MI) setting were highly successful in the pre-thrombolytic
      era. Subsequently BB proved to be beneficial in post-thrombolytic MI in long-term
      use. In stable angina BB gives good symptomatic relief primarily by reducing
      myocardial oxygen demand. In the set-up of unstable angina/non-ST elevation MI
      they prevent arrhythmia and progression to ST elevation MI. BB have also been
      shown to retard the progression of atherosclerosis. In congestive cardiac failure
      (CCF) they are now the first-line drugs with ACE inhibitors to impart prognostic
      benefit. Their role in improving outcome of cardiac and non-cardiac surgeries has
      found good evidence and recommendation. But in the field where BB have scored
      maximally, ie, in hypertension, their role is recently debated. But the
      unchallenged fact remains that in presence of any form of coronary artery
      disease, BB are the most preferred class of drugs to treat hypertension.

PMID- 21180303
TI  - Safety and tolerability of beta-blockers: prejudices & reality.
AB  - Beta-blockers (BB) substantially improve survival in chronic heart failure and
      after myocardial infarction. However, concern about side-effects may deter
      clinicians from prescribing these life-saving drugs. In reality, absolute
      contraindications are rare. Only 3-5% of patients are intolerant because of
      hypotension or bradycardia. Data from randomized controlled trials and
      retrospective studies show that most patients eligible to receive BB tolerate
      them well. BB are not contraindicated in chronic obstructive pulmonary disease
      (COPD); in fact, these patients also benefit because of their high cardiovascular
      risk. In patients with COPD, as in the elderly, BB should be started at a low
      dose and uptitrated slowly. Monitoring of lung function during initiation is
      important, as undiagnosed coexistent asthma could be revealed. When patients are
      unaware of the drug in use, erectile dysfunction (ED) is reported no more often
      with BB than with any other drug prescribed for heart failure or hypertension.
      However, when patients are aware of the potential side-effects of BB, the
      resultant anxiety may cause ED. Patients should be reassured that BB prolong life
      and in the great majority are not the cause of ED, which may rather be related to
      the underlying disease (diabetes, hypertension, and atherosclerosis).

PMID- 21180304
TI  - Beta blockers in arrhythmias: when and where to use?
AB  - Beta blockers are often the first line of medications used in treatment of
      arrhythmias. Their role has been established in treatment of Supraventricular
      tachycardia (SVT) and Ventricular tachyarrhythmias (VT). Beta Blockers are also
      used as prophylactic medications in SVT, VT and Sudden Cardiac Arrest survivors.
      They are important components of treatment in the management of VT storms, Atrial
      Fibrillation, arrhythmias during pregnancy, arrhythmias associated with
      congenital heart disease, Long QT syndrome, arrhythmias in cardiomyopathies and
      post-cardiac surgery arrhythmias.The choice of drug, dose and route of
      administration depends on the type of arrhythmia and clinical presentation and
      demographics of the patient.

PMID- 21180305
TI  - Beta blockers & left ventricular hypertrophy regression.
AB  - Left ventricular hypertrophy (LVH) particularly in hypertensive patients is a
      strong predictor of adverse cardiovascular events. Identifying LVH not only helps
      in the prognostication but also in the choice of therapeutic drugs. The
      prevalence of LVH is age linked and has a direct correlation to the severity of
      hypertension. Adequate control of blood pressure, most importantly central aortic
      pressure and blocking the effects of cardiomyocyte stimulatory growth factors
      like Angiotensin II helps in regression of LVH. Among the various
      antihypertensives ACE-inhibitors and angiotensin receptor blockers are more
      potent than other drugs in regressing LVH. Beta blockers especially the newer
      cardio selective ones do still have a role in regressing LVH albeit a minor one.
      A meta-analysis of various studies on LVH regression shows many lacunae. There
      have been no consistent criteria for defining LVH and documenting LVH regression.
      This article reviews current evidence on the role of Beta Blockers in LVH
      regression.

PMID- 21180307
TI  - Betablockers in combination with other antihypertensives.
AB  - Betablockers (BB) have been recognized as effective antihypertensive agents.
      Recent meta analysis of various hypertension trials have brought to light the
      inferiority of BB compared to other antihypertensives as a first line monotherapy
      agent. Combination of BB with dihydropyridine Calcium Channel Blocker (CCB) has
      been especially effective in smooth control of BP. Combination of diuretics with
      BB should be avoided in patients with dyslipidaemia and in those prone to develop
      diabetes. BB can be combined with vasodilators and alpha blockers with good
      therapeutic benefit. BB with angiotensin converting enzyme inhibitors/angiotensin
      receptor blockers (ACEI/ARB) is not an ideal combination as both the drugs act in
      the renin-angiotensin system. However, in hypertension with certain specific
      clinical situation this combination is useful. BB as a monotherapy agent is being
      less preferred in the treatment of hypertension based on recent evidence while in
      suitable combination it is a valuable antihypertensive.

PMID- 21180306
TI  - Chirally pure S-metoprolol--place in therapy.

PMID- 21180308
TI  - Beta blockers in acute myocardial infarction.

PMID- 21180309
TI  - Non cardiac effects of beta blockers.

PMID- 21180311
TI  - A strategy to cross radial fore-arm loop during coronary angiogram using trans
      radial approach.

PMID- 21180310
TI  - Peri-operative cardiac assessment & rationale for use of beta-blockers.

PMID- 21180312
TI  - Sgarbossa criteria and acute myocardial infarction.
AB  - Diagnosis of acute ST-elevation myocardial infarction in the presence of left
      bundle branch block is difficult. present a case of acute myocardial infarction
      with LBBB diagnosed and treated using the Sgarbossa criteria.

PMID- 21180313
TI  - "A case of cardiac amyloidosis with syncope".
AB  - A 56 year gentleman referred to our hospital for evaluation of syncope. He was
      seen previously at a local clinic and treated for cardiac failure with diuretics
      and was doing well on medication. He started having recurrent episode of syncope.
      He had his last visit to the local physician three days prior to admission when
      he had palpitation and was prescribed digoxin in addition to the usual medicine.
      Patient started having syncope from 3rd day and was referred to our hospital for
      evaluation. Patient's electrocardiogram as well as echocardiography was a
      classical finding of cardiac amyloidosis and a fat pad biopsy confirmed the
      diagnosis. After withdrawing digoxin and after two days on pacemaker, the patient
      regained normal heart rate and was discharged on diuretics.

PMID- 21180316
TI  - Intercoronary communication between right and left coronary artery with
      bidirectional flow--a rare angiographic finding.
AB  - Intercoronary artery continuity is a rare variant of coronary circulation. Here
      we report a case where we found an intercoronary communication between the left
      and the right coronary artery. Right coronary angiogram showed filling of the
      left coronary artery and the left coronary angiogram showed filling of the distal
      right coronary artery, demonstrating bidirectional flow. The coronary arteries
      were free of atherosclerotic occlusive disease. The case is reported for its
      rarity.

PMID- 21180314
TI  - Thrombosuction with export aspiration catheter during PCI in acute MI.
AB  - The angiographic demonstration of thrombus laden LAD in a ventilated young man
      with IABP (to combat cardiogenic shock) demanded thrombosuction. Following
      thrombosuction no significant lesion was visible that could have mandated PTCA
      Stenting. Follow-up coronary angiography in this hyperhomocysteinaemic young
      subject after one and a half month revealed normal coronaries. Thrombosuction
      alone unaccompanied by any other additional intervention is infrequently
      reported.

PMID- 21180315
TI  - Percutaneous balloon mitral valvuloplasty with bilateral carotid protection in 2
      cases of left atrial thrombus.
AB  - We present 2 cases of mitral stenosis with left atrial thrombus who underwent
      Balloon Mitral Valvotomy with bilateral carotid protection using SpiderFX, distal
      protection devices to minimize the risk of neuroembolic stroke. One patient was
      critical MS in congestive heart failure with a highly mobile left atrial
      appendage clot (LAA) and the second patient was a young female who declined
      surgery and had an LAA clot which did not respond to warfarin therapy.

PMID- 21180317
TI  - Managing competition in the medical profession.

PMID- 21180318
TI  - An ounce of prevention: using employment agreements to curb litigation costs.
AB  - This article is offered as food for thought in light of current Delaware case
      law. The reader is cautioned that the law varies by jurisdiction and that it
      evolves over time. This article is not intended as, and should not be construed
      as, legal advice. Rather, it discusses considerations which may be addressed with
      legal counsel in the course of drafting individualized employment agreements.
      Physicians and employers are urged to seek legal counsel to ensure that their
      agreement reflects the intent of each party and the law as it exists when the
      contract is executed.

PMID- 21180319
TI  - Why hospitalists? Why not you?

PMID- 21180320
TI  - Primary health care.

PMID- 21180321
TI  - Nursing on the edge of despair.

PMID- 21180322
TI  - Nurse led pressure injury research centre.

PMID- 21180323
TI  - Student errors on clinical placement: who takes the rap?

PMID- 21180324
TI  - Love of nursing and film combined makes for an interesting story.

PMID- 21180325
TI  - Revolution road: the challenging journey to primary health care.

PMID- 21180327
TI  - Male socialisation and health care behaviour.

PMID- 21180326
TI  - Managing deterioration through high fidelity simulation.

PMID- 21180328
TI  - The condom credit card (CCCard) strategy.

PMID- 21180329
TI  - Research offers support for gay men.

PMID- 21180330
TI  - Screening for depression in general practice.

PMID- 21180331
TI  - Wellbeing and happiness--worth striving for.

PMID- 21180332
TI  - Time to care must not be jeopardised by NHS job cuts.

PMID- 21180333
TI  - Complaints rise in wake of media focus.

PMID- 21180334
TI  - Veterinary surgeons receive more pain relief education than nurses.

PMID- 21180335
TI  - Postoperative pain 1: understanding the factors affecting patients' experiences
      of pain.
AB  - Management of postoperative pain is complex and multidimensionalandits effective
      management presents challenges to nurses. Failure to control pain can result in
      long term complications, including chronic post surgical pain. This first
      article, in a two part series, explores the physiological mechanism involved in
      the perception of pain and the role of psychological and environmental influences
      on how patients respond to it. Part 2, to be published next week, explores the
      principles of patient assessment and management of postoperative pain.

PMID- 21180336
TI  - Using a campaign to promote safer medicines practice among healthcare
      professionals.
AB  - The Chesterfield Royal Hospital Foundation Trust has a work plan to improve the
      safe administration of medicines throughout the hospital. This includes measures
      to raise nurses' awareness of the risks associated with the administration of
      medicines, and initiatives to improve safety. Last year, two focus groups were
      held with qualified nurses from across the hospital to find out how they felt
      that practice could be made safer and more effective for patients. The nurses
      suggested that an educational campaign be organised to highlight best practice
      and to encourage nurses to think differently about medicines administration. This
      paper summarises the content and outcome of the campaign.

PMID- 21180337
TI  - Caring for adults with chronic heart failure: rapid diagnosis and enhanced
      management.

PMID- 21180338
TI  - Using home telehealth to empower patients to monitor and manage long term
      conditions.
AB  - This article describes a pilot telehealth project in Swansea where patients with
      heart failure and chronic obstructive pulmonary disease were provided with
      telehealth monitoring equipment. While early evaluation points to some potential
      economic benefits, supporting patient empowerment was a significant outcome.

PMID- 21180339
TI  - Developing nursing practice, treatment and support services for ageing drug
      users.
AB  - BACKGROUND: Ageing drug users are a growing population who have problems
      accessing services and support. AIM: To inform practice, service development and
      further research on ageing drug users. METHOD: Qualitative interviews with 11
      people aged 49-61 who were in contact with voluntary sector drug
      treatmentservices. RESULTS: Individuals reported mixed experiences of the primary
      and hospital care they received. Some felt stigmatised by healthcare
      professionals, but others said their drug use was acknowledged and people were
      compassionate towards them. CONCLUSION: Nurses and other care professionals
      working with older people must be sensitive to the needs of this population, and
      attempt to tailor care and services to their needs.

PMID- 21180340
TI  - We cannot commission without your expertise.

PMID- 21180341
TI  - The X factor is not the only thing making people cross.

PMID- 21180342
TI  - Nuclear energy.
AB  - The technical principles and practices of the civil nuclear industry are
      described with particular reference to fission and its products, natural and
      artificial radioactivity elements principally concerned and their relationships,
      main types of reactor, safety issues, the fuel cycle, waste management, issues
      related to weapon proliferation, environmental considerations and possible future
      developments.

PMID- 21180343
TI  - State of the art of photovoltaic technologies.
AB  - Our sun is the only sustainable energy source large enough to supply carbon
      neutral energy to meet humanity's entire energy demand. However there is a large
      gap between Europe's solar energy use (less than 1% of the total) and the
      enormous, untapped potential of the sun. There could be several reasons listed
      why it is so-social, political, technological--but the fundamental reason is
      insufficient efficiency of sunlight-to-energy conversion devices manufactured
      from inexpensive materials thus preventing large scale uptake. Along with thermal
      and photoelectrochemical sunlight-to-energy conversion, photovoltaics--an
      approach of converting sunlight directly into electricity--is probably most
      mature for contributing to the increasing renewable energy use. This review
      details the general operating principles of the main types of photovoltaic
      devices, device efficiencies and the limitations of each technology with due
      consideration of the commercial requirements and uptake within the global
      renewable energy sector. There is also a section dedicated to emerging research,
      particularly within the European academic research base, focussing on overcoming
      some of the limitations associated with current photovoltaic technology.

PMID- 21180344
TI  - The overlooked link between non-virus microbes and cancer.
AB  - For more than a hundred years every generation of microbiologists has isolated so
      called "cancer germs" from animal and human tumours and some cancer researchers
      have claimed that these organisms cause cancer and also that in some cases,
      vaccines could be developed from them to treat this dreaded disease. Despite this
      longstanding evidence linking microbes and cancer, today's cancer experts believe
      that, except in the case of a limited number of virus-cancers, microbes do not
      play an important causative role in cancer Here, the evidence linking non-virus
      microorganisms with cancer is discussed and a plea is made that more research
      interest and funding be directed towards the cancer germ hypothesis.

PMID- 21180345
TI  - The human mind: origin in geometry.
AB  - Within 53 years after the public acceptance of Mendel's laws (in 1900), the
      genetic material was identified and described (by Watson and Crick). Today, 53
      years after the modern era began in the scientific study of language (with
      Chomsky's Syntactic structures), there is no agreement as to whether universal
      grammar exists, or whether language as such exists at all, that is, there is no
      agreement as to which square is square-one. Under the circumstances, a new
      approach is justified. It is the goal of this paper to place the scientific study
      of mind, language and brain onto a theoretical basis, beginning with naturally
      occurring human language. The human mind has two major components, one with its
      antecedents in biology and behaviour the other with its antecedents in geometry.
      It is the geometric component, consisting of language, tool-use, the mathematical
      sense, and the sense of truth and falsity, that distinguishes and defines the
      human being. Thus the constructions of language conform to the commutative,
      associative and distributive laws, and have their ultimate source in geometry.
      Equations have a symmetrical deep-structure based on the fact that one side is
      "equal" to the other: The "equals" symbol represents the axis of symmetry, and
      functions as a kind of main verb. The deep structure of the ordinary sentence is
      derived by moving the attachment for the "equals" to one of the branches,
      generating the asymmetrical Subject-Verb-Object relationship. Tool-use, with its
      Subject (the tool), Verb (movement of the tool), and Object (the workpiece), and
      manipulation of mental images, is an extension of the sentence. The sense of
      truth and falsity shares a common source with the right and wrong answers of
      arithmetic.

PMID- 21180346
TI  - The art of writing good research proposals.
AB  - Whilst scientists are by default motivated by intellectual challenges linked to
      the area of their interest rather than have an interest in the financial
      component related to their work, the reality of today is that funding for their
      work does not come automatically More and more governments provide project
      related funding rather than multipurpose funding that covers the total annual
      costs of a research performing entity (such as a university department). So, like
      it or not, researchers have to present their research ideas and convince funding
      bodies about the usefulness and importance of their intended research work.
      Writing the research proposal is not simply typing words and punctuation. It
      requires succinctly and clearly chronicling the facts, as well as crafting a
      convincing line of reasoning for funding the project. For the best result, both
      the logical, verbal left side of the brain and the intuitive, creative right side
      of the brain need to work as a team. This article covers the process of writing a
      proposal, from research idea to submission to the funding body. The key to good
      writing is linking the text into a logical project flow. Therefore, in the early
      stage of writing an RTD proposal, developing the chain of reasoning and creating
      a flow chart is recommended to get a clear overview of the entire project and to
      visualise how the many work packages are connected.

PMID- 21180347
TI  - Risk assessment of repetitive movements in the citrus fruit industry.
AB  - Musculoskeletal disorders are injuries of the muscles, nerves, tendons,
      ligaments, joints, cartilage, or spinal discs and are often classified as soft
      tissue injuries. They are the result of chronic or gradual development and are
      not caused by acute incidents such as slips, trips, or falls. The significance of
      this phenomenon prompted us to carry out a broader study of pathologies
      attributable to repetitive movements in the upper limbs within the citrus growing
      industry. Calabria, a very important region for citrus fruit growing in Italy,
      was chosen as the study area. The study analyzed the risks of repetitive
      movements for 180 workers on 35 different farms using the OCRA (Occupational
      Repetitive Actions) checklist method By analyzing the scores obtained in the
      different work phases, it was possible to determine the tasks that incur more
      risk in the citrus fruit industry. The OCRA checklist considers all the
      repetitive tasks involved in a complex job and estimates the level of exposure to
      each worker. In support of the specific aims of the present study, it is possible
      to identify a series of working conditions for which the level of risk may be
      reasonably estimated and for which it is possible to adopt a checklist system.
      The results of this study suggest that there must be a significant increase in
      the use of effective ergonomic interventions in the workplace in order to attain
      reductions in the number of local musculoskeletal complaints.

PMID- 21180348
TI  - The farm apprentice: agricultural college students recollections of learning to
      farm "safely".
AB  - A consistent message in the farm safety literature is the need to develop
      effective interventions to manage the unacceptably high rate of injury and death
      among farm children. To better understand the influence of childhood farm
      experiences on safety beliefs, attitudes, and practices, semi-structured
      interviews were conducted with 24 farm youth attending the Nova Scotia
      Agricultural College. The interviews were designed to elicit information
      pertaining to participants' earliest memories of involvement in farm activities,
      the decision-making processes that led them to assume work-related
      responsibilities, and the roles that their parents played in their safety
      training. A common theme of experiencing childhood as a "farm apprentice" emerged
      across all narratives whereby farm activities were learned primarily through
      observational learning and modeling of parents and then mastered through
      repetition. As "farm apprentices," the youths' involvement in dangerous
      activities such as tractor driving and livestock handling began at early ages,
      with very little formal training and supervision. Although participants clearly
      described themselves as being exposed to dangerous activities, they believed that
      they had the capacity to control the risks and farm safely. Based on our
      findings, the concept of the "farm apprentice" appears to be integral to the
      social context of the farming community and should be considered in the design of
      interventions to reduce child injury and death.

PMID- 21180349
TI  - Operator assessment of tractor roll angle with and without a tractor stability
      visual feedback device.
AB  - According to a 2004 National Institute for Occupational Safety and Health (NIOSH)
      report, approximately 250 to 350 fatalities occur each year due to incidents
      involving production agriculture workers and tractors. Tractor overturns account
      for about 150 to 200 of these deaths. The goals of this project were to study
      operators' understanding of tractor roll angles and test a device to effectively
      deliver stability information to the tractor operator. This project required the
      design and construction of a full-scale tractor cab roll simulator that was used
      to identify lateral roll angles at which volunteer participants felt
      uncomfortable, as well as lateral roll angles at which they would no longer
      operate a tractor. In addition, the participants performed a series of tasks to
      test the functionality of a visual slope indicator that was designed to help them
      estimate slope angles. The project tested 231 tractor operators' perceptions of
      safe operation on side slopes and 128 participants' interactions with the visual
      slope indicator. Testing showed that the visual slope indicator was able to
      influence the angle estimations of the novice tractor operator population and
      helped the entire population of participants more accurately rank the simulator
      scenarios.

PMID- 21180350
TI  - Factors associated with the prevalence of non-ROPS tractors on farms in the U.S.
AB  - Rollover protective structures (ROPS) are an effective engineering control known
      to prevent tractor overturn deaths, the leading cause of occupational fatalities
      for farmers and farm workers in the U.S. However, the use of ROPS is known to
      vary greatly from farm to farm. A national sample of 11,458 farm operators from
      the 2004 Occupational Injury Surveillance of Production Agriculture (OISPA)
      survey was used to assess the association between the prevalence of ROPS and ten
      farm operator and farm demographic variables using logistic regression. The
      variable were: operator's age, operator's sex, operator's education, farm sales,
      full- or part-time farming, acreage, type of operation, number of hired workers,
      number of injuries, and region. All ten variables were found to have significant
      associations with the prevalence of non-ROPS tractors on farms in the univariate
      logistic regressions. For the multivariate model, all variables except for the
      sex of the farm operator remained significant. Farms with less than three adult
      injuries, no hired workers, less than 300 acres in size, a Midwest location, and
      a primary farm type of tobacco, fruit and nuts, dairy, or poultry and eggs all
      had adjusted odds ratios of 2 or greater. Increasing the prevalence of ROPS
      equipped tractors is essential for reducing the leading cause of death on farms,
      tractor overturns. Economic factors play a major role in the prevalence and
      distribution of non-ROPS tractors on farms. The identified associations can be
      used to effectively target areas of the U.S. for ROPS promotion activities.

PMID- 21180351
TI  - Injury surveillance for youth on farms in the U.S., 2006.
AB  - In order to provide injury surveillance for youth on farms in the U.S., the
      National Institute for Occupational Safety and Health (NIOSH), in partnership
      with the USDA, developed the Childhood Agricultural Injury Survey (CAIS). CAIS
      data for all youth less than 20 years of age on farms have been collected for the
      calendar years of 1998, 2001, 2004, and 2006. CAIS data from 2006 indicated that
      an estimated 30.7 million youth lived on, worked on, or visited U.S. farms. These
      youth experienced almost 23,000 injuries while on the farm. The majority of these
      injuries occurred to males (15,223) and youth between the ages of 10 and 15 years
      (10,158). Approximately 25% (5,773) of the injuries were related to work being
      done on the farm. Youth living on the farm incurred 51% (11,654) of the injuries,
      hired youth sustained 6% (1,363), and 40% were to visiting youth (9,729).
      Although youth injuries on farms have declined by 30% since 1998, the numbers are
      still unacceptably high. Further indepth evaluation of subsets of the youth
      population may serve to better direct safety intervention programs and research.

PMID- 21180352
TI  - Vestibular stimulation affects optic-flow sensitivity.
AB  - Typically, multiple cues can be used to generate a particular percept. Our area
      of interest is the extent to which humans are able to synergistically combine
      cues that are generated when moving through an environment. For example, movement
      through the environment leads to both visual (optic-flow) and vestibular
      stimulation, and studies have shown that non-human primates are able to combine
      these cues to generate a more accurate perception of heading than can be obtained
      with either cue in isolation. Here we investigate whether humans show a similar
      ability to synergistically combine optic-flow and vestibular cues. This was
      achieved by determining the sensitivity to optic-flow stimuli while physically
      moving the observer, and hence producing a vestibular signal, that was either
      consistent with the optic-flow signal, eg a radially expanding pattern coupled
      with forward motion, or inconsistent with it, eg a radially expanding pattern
      with backward motion. Results indicate that humans are more sensitive to motion
      in-depth optic-flow stimuli when they are combined with complementary vestibular
      signals than when they are combined with conflicting vestibular signals. These
      results indicate that in humans, like in nonhuman primates, there is perceptual
      integration of visual and vestibular signals.

PMID- 21180353
TI  - Enhancing implicit change detection through action.
AB  - Implicit change detection demonstrates how the visual system can benefit from
      stored information that is not immediately available to conscious awareness. We
      investigated the role of motor action in this context. In the first two
      experiments, using a one-shot implicit change-detection paradigm, participants
      responded to unperceived changes either with an action (jabbing the screen at the
      guessed location of a change) or with words (verbal report), and sat either 60 cm
      or 300 cm (with a laser pointer) away from the display. Our observers guessed the
      locations of changes at a reachable distance better with an action than with a
      verbal judgment. At 300 cm, beyond reach, the motor advantage disappeared. In
      experiment 3, this advantage was also unavailable when participants sat at a
      reachable distance but responded with hand-held laser pointers near their bodies.
      We conclude that a motor system specialized for real-time visually guided
      behavior has access to additional visual information. Importantly, this system is
      not activated by merely executing an action (experiment 2) or presenting stimuli
      in one's near space (experiment 3). It is activated only when both conditions are
      fulfilled, which implies that it is the actual contact that matters to the visual
      system.

PMID- 21180354
TI  - The potential hedonic role of olfaction in sexual selection and its dominance in
      visual cross-modal interactions.
AB  - Perfumes are commonly used to cover body odour, or to provide a positive,
      attracting, and interesting impact, or a smell that belongs to a social group. A
      role in sexual communication of such non-pheromonal olfactory cues has been
      suggested in the literature. However, there remain the questions whether these
      stimuli are involved in human chemosexual communication and, if so, at what
      level, and whether they interact with other sensorial modalities, in particular
      vision. To answer these, we investigated the influence of male and female
      perfumes as nonconscious stimulation during visual assessments of a range of
      facial qualities across and within the sexes. The female subjects were in their
      ovulatory phase, to avoid changes in perception across the menstrual cycle. Our
      data indicate that non-pheromonal olfactory cues are potentially involved in mate
      choice and may elicit strong hedonic responses that can dominate visual signs,
      with a cross-modal interaction.

PMID- 21180355
TI  - Lateral masking in cycling displays: the relative importance of separation,
      flanker duration, and interstimulus interval for object-mediated updating.
AB  - A central bar repeatedly presented in alternation with two flanking bars can lead
      to the disappearance of the central bar. Recently it has been suggested that this
      masking effect could be explained by object-mediated updating: the information
      from the central bar is integrated into the representation of the flankers,
      leading not only to the disappearance of the central bar as a separate object,
      but also to the perception of the flankers in apparent motion between their real
      position and the position of the central bar. This account suggests that the
      visibility of the central bar should depend on the same factors as those that
      influence the construction and maintenance of object representations. Therefore
      separation between central bar and flankers should not influence visibility as
      long as the time interval between them is adequate to make an interpretation of
      the scene in terms of one object moving from one location to the other possible
      location. We found that if the time interval between the central bar and the
      flankers is neither too short nor too long, the central bar becomes invisible
      even at large separations. These findings are inconsistent with traditional
      accounts of the cycling lateral masking displays in terms of local inhibitory
      mechanisms.

PMID- 21180356
TI  - Performance and ease influence perceived speed.
AB  - According to the action-specific perception account, perception is a function of
      optical information and the perceiver's ability to perform the intended action.
      While most of the evidence for the action-specific perception account is on
      spatial perception, in the current experiments we examined similar effects in the
      perception of speed. Tennis players reproduced the time the ball traveled from
      the feeder machine to when they hit it. The players judged the ball to be moving
      faster on trials when they hit the ball out-of-bounds than on trials where they
      successfully hit the ball in-bounds. Follow-up experiments in the laboratory
      showed that participants judged virtual balls to be moving slower when they
      played with a bigger paddle in a modified version of Pong. These studies suggest
      that performance and task ease influence perceived speed.

PMID- 21180357
TI  - Rapid learning by walking observers wearing a reversing or inverting prism.
AB  - We measured the initial rapid learning of walking observers who wore an up-down
      inverting or left-right reversing prism. This prism-walking version of the
      'mirror-drawing' experiment revealed that the learning curve as a function of the
      trial number was the same as that typically acquired from a traditional mirror
      drawing experiment. We suggest that the initial short-term learning process
      involved in prism walking is similar to that in mirror drawing and is related to
      the high-level decision-making process involved in visuo-motor planning of
      actions with feedback from transformed vision.

PMID- 21180358
TI  - The role of expectation and probabilistic learning in auditory boundary
      perception: a model comparison.
AB  - Grouping and boundary perception are central to many aspects of sensory
      processing in cognition. We present a comparative study of recently published
      computational models of boundary perception in music. In doing so, we make three
      contributions. First, we hypothesise a relationship between expectation and
      grouping in auditory perception, and introduce a novel information-theoretic
      model of perceptual segmentation to test the hypothesis. Although we apply the
      model to musical melody, it is applicable in principle to sequential grouping in
      other areas of cognition. Second, we address a methodological consideration in
      the analysis of ambiguous stimuli that produce different percepts between
      individuals. We propose and demonstrate a solution to this problem, based on
      clustering of participants prior to analysis. Third, we conduct the first
      comparative analysis of probabilistic-learning and rule-based models of
      perceptual grouping in music. In spite of having only unsupervised exposure to
      music, the model performs comparably to rule-based models based on expert musical
      knowledge, supporting a role for probabilistic learning in perceptual
      segmentation of music.

PMID- 21180359
TI  - Head-body ratio as a visual cue for stature in people and sculptural art.
AB  - Body size is crucial for determining the outcome of competition for resources and
      mates. Many species use acoustic cues to measure caller body size. Vision is the
      pre-eminent sense for humans, but visual depth cues are of limited utility in
      judgments of absolute body size. The reliability of internal body proportion as a
      potential cue to stature was assessed with a large sample of anthropometric data,
      and the ratio of head height to body height (HBR) was found to be highly
      correlated with stature. A psychophysical experiment was carried out to
      investigate whether the cue actually influences stature judgments. Participants
      were shown pairs of photographs of human figures in which HBR had been
      manipulated systematically, and asked to select the figure that appeared taller.
      Results showed that figures with a relatively small HBR were consistently
      perceived as taller than figures with a relatively large HBR. Many classical
      statues such as Michelangelo's David depart from the classical proportions
      defined in Leonardo's Vitruvian Man. A supplementary experiment showed that
      perceived stature in classical statues also depends on HBR. Michelangelo's David
      was created with the HBR of a man 165 cm (5 ft 5 in) tall.

PMID- 21180360
TI  - Ouch! My phantom leg jumps/hurts when you stab "my" virtual hand.
AB  - Pain synaesthetes experience pain in a presensitised region when observing or
      imagining another person in pain. We conducted an upper-limb embodiment study
      using a modified rubber-hand illusion in which lower-limb amputees originally
      participated as control subjects for the upper-limb amputees. While we found all
      subjects experienced topographic illusory sensations, we also serendipitously
      found that lower-limb amputee pain synaesthetes experienced pain or a motor
      response in their phantom leg when the embodied hand was threatened (e.g., with a
      retractable knife, mousetrap, or syringe) or submitted to high-frequency
      stimulation (e.g., vibration). Embodiment illusions were brought about by
      touching, manipulating, or threatening a rubber or real hand which was observed
      through a mirror so that it was superimposed upon the target hand (phantom hand
      for upper-limb amputees, or real hand in others). Participants included eight
      pain synaesthetes (six lower-limb amputees, one upper-limb amputee, and one
      nonamputee), and thirty-one controls (eight lower-limb amputees, twelve upper
      limb amputees, and eleven nonamputees). We documented participant's subjective
      reports, together with quantitative measures including the Questionnaire Measure
      of Emotional Empathy. We found no association between pain synaesthesia and
      empathy scores. On the basis of related literature we suggest that pain
      synaesthetes likely experienced phantom-leg pain because (a) the motor system was
      already engaged during visual capture; (b) threatening stimuli, to which they are
      hyper-vigilant, triggered avoidance or 'escape' motor schemata; and (c) there
      could be no feedback confirming that initiated motor schemata for the phantom
      limb were successfully performed. Ultimately, we have further defined this new
      condition, synaesthesia for pain, as not only having a sensory pain component,
      but also a key motor component, manifesting itself in avoidance, contraction, and
      withdrawal 'actions'.

PMID- 21180361
TI  - Eyes pursue moving objects, not retinal motion signals.
AB  - For smooth-pursuit eye movements, a moving target is necessary, but we show that
      it is not sufficient. Observers pursued targets that appeared to move in one
      direction even though they really moved in another. Changes in perceived
      direction did not disrupt pursuit eye movements, but motion-based failures in
      object parsing did.

PMID- 21180362
TI  - The brightness of diamonds.
AB  - A brightness illusion and transparency effects are described for configurations
      comprising alternating black and white bars on which are superimposed mid
      luminance shapes (diamonds and hexagons). The resulting phenomena are predictable
      by Anderson's 'scission theory', which is thus given further support.

PMID- 21180363
TI  - Judging a book by its cover: the unconscious influence of pupil size on consumer
      choice.
AB  - Past research suggests that men perceive women with large pupils as especially
      attractive. We employed an innovative methodology to examine whether this effect
      influences consumer decision-making. A popular psychology book was published with
      two slightly different front covers. Both covers contained the same photograph of
      a woman; however, the woman's pupils on one cover were digitally enlarged.
      Readers indicated whether they were male or female, and whether they possessed
      the cover with small or large pupils. A significantly greater percentage of men
      than women had chosen the cover with the large pupils. None of the participants
      who attempted to guess the nature of the experiment was correct, suggesting that
      the influence exerted by pupil size was unconscious. These findings provide
      further support for the notion that people's judgments are unconsciously swayed
      by pupil size, and demonstrate that this effect operates in a real world setting.

PMID- 21180364
TI  - Using the CLOX drawing task to educate the public of the effects of hearing loss.
AB  - We describe a task used to educate the public on the importance of hearing and
      the experience of hearing loss. During an open day at Nottingham University,
      participants were presented with verbal instructions (with or without a
      background masker) and asked to draw the image of a clock face as accurately as
      possible. Poorest performance was observed when the instructions were presented
      with a background masker. We suggest that the task could be applied effectively
      by healthcare professionals who aim to educate younger individuals of the
      difficulties associated with hearing loss.

PMID- 21180365
TI  - Sex difference in subjective duration of looming and receding sounds.
AB  - Looming sounds (sounds increasing in intensity over time) are more salient than
      receding sounds (a looming sound reversed in time). For example, they are
      estimated as being longer, louder, and more changing in loudness than receding
      sounds. Some authors interpret the looming salience as evolutionarily adaptive,
      because it increases the margins of safety of the perceiver in the case of
      preparatory behaviours (e.g., a motor reaction to an approaching sound source).
      Recently, Neuhoff et al (2009, Journal of Experimental Psychology: Human
      Perception and Performance 35 225-234) found that females more than males show
      overestimation of the spatiotemporal properties of virtually simulated looming
      sound sources. Here, I investigated whether the sex difference could be observed
      for the subjective duration of looming and receding sounds, and found that
      females more than males overestimate the duration of looming sounds in comparison
      to receding sounds.

PMID- 21180366
TI  - Did Venus have long legs? Beauty standards from various historical periods
      reflected in works of art.
AB  - Research on perception of attractiveness of leg-to-body ratio (LBR) described
      here has shown that people prefer relatively long-legged silhouettes
      (particularly while assessing women). The LBR of attractive women over historical
      periods (analyses of attractive silhouettes from paintings, sculptures, etc) has
      been more changeable than that of men. The findings reported here might represent
      evidence against the cross-cultural universality of the attractiveness of long
      legs.

PMID- 21180367
TI  - Making a difference.

PMID- 21180368
TI  - Tolvaptan: any evidence of efficacy in SIADH?
AB  - The cornerstone of treatment for syndrome of inappropriate antidiuretic hormone
      secretion (SIADH) is fluid restriction. Demeclocycline is sometimes used but its
      efficacy is based solely on laboratory endpoints. This drug also has the adverse
      effects shared by all tetracyclines. Tolvaptan antagonises receptors for arginine
      vasopressin, a hormone that regulates blood sodium levels by stimulating renal
      water resabsorption. Tolvaptan is now authorised in the European Union for the
      treatment of hyponatraemia due to SIADH. Clinical evaluation of tolvaptan in this
      setting is based on two comparative double-blind placebo-controlled trials
      including a total of 448 patients with SIADH or hyponatraemia from various other
      causes. The two trials were combined for analysis. However, because of major
      methodological flaws, no firm conclusions can be drawn concerning the efficacy in
      SIADH patients. It remains to be shown that tolvaptan improves symptoms of
      hyponatraemia (especially neuropsychiatric disorders) or even that it corrects
      hyponatraemia in these patients. The adverse effects observed in clinical trials
      were predictable, given the mechanism of action, and included thirst and dry
      mouth (respectively 16% and 8.4% of patients), hypernatraemia (1.7%), pollakiuria
      and polyuria. Tolvaptan is metabolised by the cytochrome P450 isoenzyme CYP 3A4,
      hence a high risk of pharmacokinetic interactions. In summary, there is no reason
      to use tolvaptan to treat the syndrome of inappropriate antidiuretic hormone
      secretion: its efficacy on symptoms or even on sodium levels has not been
      demonstrated, and its adverse effect profile is poorly documented. It is better
      to concentrate on non-drug management.

PMID- 21180369
TI  - Ofatumumab: chronic lymphocytic leukaemia: a last resort.
AB  - About 50% of patients with symptomatic chronic lymphocytic leukaemia in whom
      chlorambucil and fludarabine have failed die within 6 to 9 months. In addition to
      appropriate palliative care, alemtuzumab may offer patients a few extra months of
      life, but at a cost of several serious adverse effects. Ofatumumab, a monoclonal
      antibody similar to rituximab, has been authorised in the United States for the
      treatment of patients with chronic lymphocytic leukaemia refractory to
      fludarabine and alemtuzumab. The European Medicines Agency has issued a
      favourable opinion on marketing authorisation of ofatumumab in this setting.
      Clinical assessment of ofatumumab is based on an interim subgroup analysis of a
      non-comparative trial in 154 patients. Fludarabine and alemtuzumab therapy had
      failed in 59 patients. The median overall survival time in this subgroup of 59
      patients was 13.7 months, and the time to progression was 5.7 months. Thirty-one
      of these 59 patients had non-specific symptoms of leukaemia, which disappeared
      for at least 2 and 6 months in respectively 48% and 23% of cases. The adverse
      effect profile of ofatumumab appears similar to that of rituximab, and includes
      hypersensitivity reactions, infections, cardiac disorders and neutropenia. In
      practice, despite the scarcity of data, the use of ofatumumab seems to be
      justified for patients who have no other valid therapeutic options, but more data
      are needed.

PMID- 21180370
TI  - Parecoxib and fatal skin reactions: when will this drug be withdrawn from the
      European Union market?

PMID- 21180371
TI  - Ketoprofen gels: unfortunately back on the French market.
AB  - Ketoprofen gels are more harmful than beneficial, and their withdrawal from the
      French market in late 2009 was a welcome measure. Unfortunately, they were back
      on the market in early 2010 following legal action. Healthcare professionals and
      patients should rely on solid evidence rather than decisions made by regulatory
      agencies or the judiciary.

PMID- 21180372
TI  - INN common stems: -mab, -ermin.

PMID- 21180373
TI  - Sildenafil and mild pulmonary arterial hypertension: unjustified risks, with no
      tangible benefit.

PMID- 21180374
TI  - Catumaxomab: malignant ascites: unjustified marketing authorisation.
AB  - The only treatment for malignant ascites in patients with refractory cancer is
      paracentesis, a procedure to relieve symptoms. Catumaxomab, a monoclonal
      antibody, is now authorised in the European Union for intraperitoneal
      administration to patients with epithelial cancers that overexpress epithelial
      cellular adhesion molecule (EpCAM) and provoke ascites unresponsive to
      chemotherapy. Clinical evaluation of catumaxomab in this setting is based on a
      comparative, randomised but unblinded trial including 258 patients. Patients in
      the catumaxomab group had four paracenteses over a 10-day period, followed by a 6
      hour intraperitoneal catumaxomab infusion, while patients in the control group
      had a single paracentesis. Catumaxomab did not extend median survival time, which
      was about two months. Methodological biases rule out any conclusions as to
      whether catumaxomab reduced the number of paracenteses needed during this short
      survival period. In this trial, 80% of patients treated with catumaxomab
      experienced serious adverse events, versus 29% of controls, resulting in
      hospitalisation in respectively about 29% versus 16% of patients. Two-thirds of
      patients had reactions linked to intraperitoneal catumaxomab infusion.
      Gastrointestinal disorders were frequent, and included abdominal pain, nausea and
      vomiting. Catumaxomab is hepatotoxic. In addition, most patients develop anti
      catumaxomab antibodies, although the clinical consequences are unclear.
      Catumaxomab therapy is inconvenient: it lasts 10 days and requires 4
      intraperitoneal infusions that last 6 hours each and require 24-hour monitoring.
      In practice, catumaxomab has more harms than benefits. It is better to focus on
      individually tailored palliative care for these terminally ill patients.

PMID- 21180375
TI  - Elderly dementia patients and neuroleptics: excess mortality.
AB  - In 2005, a meta-analysis conducted by the US Food and Drug Administration showed
      a 1% to 2% increase in mortality, in absolute values, in elderly dementia
      patients treated with so-called atypical neuroleptics than in patients not
      receiving neuroleptics. One placebo-controlled trial, two new meta-analyses, and
      several cohort studies of various sizes and designs have been published since
      2005. The double-blind placebo-controlled trial showed a statistically
      significant decline in mortality when neuroleptic therapy (risperidone or
      haloperidol in most cases) was withdrawn. One of the meta-analyses showed excess
      mortality in patients receiving atypical neuroleptics compared with those not
      receiving neuroleptics. The other meta-analysis, focusing solely on risperidone,
      showed a higher risk of vascular death than in placebo-treated patients. Four
      very large cohort studies also showed a trend towards excess mortality with
      conventional neuroleptics. In practice, as all neuroleptics have negative risk
      benefit balances in elderly dementia patients, it is best to avoid using them in
      these patients, if possible. If a neuroleptic is nonetheless prescribed,
      treatment should be for the shortest possible duration, at the minimum effective
      dose.

PMID- 21180376
TI  - High-dose methotrexate during pregnancy: risk of malformations.
AB  - Methotrexate is a cytotoxic and immunosuppressant drug mainly used in oncology
      and rheumatology. It is sometimes used at high doses to treat unruptured ectopic
      pregnancy. Methotrexate is teratogenic. Malformations reported after exposure in
      utero include: abnormalities of the skull and face, limb defects, failure of
      ossification, and congenital cardiopathy.The risk of malformations is probably
      dose-dependent and seems to be relatively low at the low weekly doses used in
      rheumatology. Three cases of malformations have been reported after failure of
      high-dose methotrexate in pregnancies that were misdiagnosed as ectopic. Two
      newborns had scoliosis, facial dysmorphism, limb malformations, or
      cardiopathy.The third newborn had minor malformations. In practice, high-dose
      methotrexate must only be used to treat ectopic pregnancy if the diagnosis has
      been confirmed. The woman should be informed of the risks to her unborn child in
      case of diagnostic error or treatment failure.

PMID- 21180377
TI  - Methotrexate during the first trimester of pregnancy.

PMID- 21180378
TI  - Drug-induced acneiform rash.
AB  - Acne is a generally mild skin condition, common among adolescents and young
      adults. Certain toxins and drugs can aggravate pre-existing acne or cause
      acneiform rash. Various pharmacological classes can cause acneiform rash.The
      eruptions usually subside after drug withdrawal, but sometimes only after several
      months.

PMID- 21180379
TI  - Tocilizumab: intestinal perforations.

PMID- 21180380
TI  - Injectable paracetamol in children: fatal confusion between milligrams and
      millilitres.

PMID- 21180381
TI  - Anaesthetic ointments: fatal overdose in adults.
AB  - Caution must be used when applying anaesthetic ointments to large areas of skin
      prior to cosmetic procedures such as laser hair removal. Overdose can have
      arrhythmogenic and proconvulsant effects. The deaths of two young women have been
      reported.

PMID- 21180382
TI  - Chemotherapy of metastatic colorectal cancer.
AB  - Without treatment, patients with inoperable or metastatic colorectal cancer have
      a median life expectancy of about 8 months. The following article is an update of
      our 2005 review of chemotherapy regimens used in metastatic colorectal cancer,
      based on the standard Prescrire methodology. In 2005, the de Gramont protocol,
      based on fluorouracil (always combined with folinic acid) plus either oxaliplatin
      (Folfox protocol) or irinotecan (Folfiri protocol), was the standard first-line
      chemotherapy in this setting. Four trials comparing monotherapy versus
      combination therapy in previously untreated patients showed that initial
      fluorouracil (or fluorouracil precursor) monotherapy, followed by the Folfox or
      Folfiri protocol in case of failure, was not associated with shorter overall
      survival. Two trials compared first-line treatment with the Folfiri regimen
      versus the Folfoxiri regimen (fluorouracil + oxaliplatin + irinotecan). One of
      these studies showed an increase in median survival with the Folfoxiri protocol
      (24 versus 17 months), but at a cost of greater neurotoxicity. The only tangible
      advantage of capecitabine and tegafur, two oral fluorouracil precursors, is their
      convenience of use. Pemetrexed was less effective and more toxic than the Folfiri
      protocol in one trial. Bevacizumab and panitumumab have yielded disappointing
      results in previously untreated patients. Neither of these monoclonal antibodies
      has yet been shown to improve overall survival. Three trials have assessed the
      addition of cetuximab to combinations consisting of fluorouracil or capecitabine
      plus oxaliplatin or irinotecan. In two of these trials, the median survival time
      of patients whose tumours carried the wild-type KRAS gene was about 3 months
      longer in the cetuximab arms, although the increase was statistically significant
      in only one trial. Cetuximab had no impact on survival time in the third trial.
      In two trials, an anti-EGFR antibody (panitumumab or cetuximab) reduced median
      survival when added to bevacizumab in previously untreated patients. When
      progression occurs after treatment with the Folfiri protocol (or equivalent), a
      combination of the Folfox protocol and bevacizumab seems to increase median
      survival time by about 2 months versus Folfox alone, but it is also more toxic.
      In patients who progress after receiving the fluorouracil + oxaliplatin
      combination (Folfox) or the fluorouracil+ irinotecan combination (Folfiri),
      neither panitumumab nor cetuximab has been shown to provide a clinically
      meaningful increase in overall survival. It remains to be shown whether these
      drugs are more effective in patients with the wild-type KRAS gene than in
      patients with KRAS mutations. In early 2010, the standard cytotoxic drugs for
      treatment of metastatic colorectal cancer are fluorouracil (combined with folinic
      acid), oxaliplatin and irinotecan. Initial combination therapy may be beneficial
      when the metastases are borderline operable. When the metastases are inoperable
      and are unlikely to become operable after chemotherapy, it seems best to begin
      treatment with single-agent fluorouracil (+ folinic acid) or capecitabine. The
      use of monoclonal antibodies in first-line treatment of patients with colorectal
      cancer is not justified. Further trials of these drugs are warranted as second
      line treatment for patients with KRAS wild-type tumours.

PMID- 21180383
TI  - Ambulatory blood pressure measurement.
AB  - Ambulatory blood pressure measurement (ABPM) consists of wearing a portable
      device connected to an armband that automatically measures blood pressure at
      regular intervals. What advantages does ambulatory blood pressure monitoring
      provide over measurement in the doctor's office, and what are the risks? To
      answer these questions, we reviewed the literature using the standard Prescrire
      methodology. Mean blood pressure recorded over 24 hours is generally lower than
      office blood pressure measurement: a value of 140/90 mmHg obtained during an
      office visit usually corresponds to a 24-hour average of 125/80 to 130/80 mmHg.
      Several cohort studies have examined the possible added prognostic value of
      ambulatory blood pressure measurement, but only one study included an appropriate
      comparator. There is no evidence that ambulatory blood pressure measurement is
      more reliable than repeated measurement during several office visits for
      predicting cardiovascular events. Only one trial has compared antihypertensive
      treatment adjustment based on ambulatory recording versus office measurements in
      terms of cardiovascular prevention. The results, which favoured ambulatory
      recording, are undermined by methodological flaws. White coat hypertension refers
      to elevated blood pressure only in the presence of a healthcare professional. A
      white coat effect suggested by a first ambulatory blood pressure measurement is
      not confirmed by a second ambulatory blood pressure measurement in over 50% of
      patients, who in fact have permanent hypertension. Ambulatory blood pressure
      measurement is inconvenient for the patient and sometimes painful. Between 2% and
      7% of patients report local adverse effects such as skin reactions and oedema. In
      practice, ambulatory recording can be a useful second-line method for measuring
      blood pressure, especially when a white coat effect is suspected, or when
      considering treatment modification for a patient with what appears to be
      refractory hypertension. When office measurements and ambulatory recording yield
      conflicting results, it should not be assumed that ambulatory blood pressure
      measurement is more reliable.

PMID- 21180384
TI  - Cardiac arrest in the out-of-hospital setting: when to halt resuscitation.
AB  - In out-of-hospital settings, when is it reasonable to halt attempts to
      resuscitate a victim of sudden cardiac arrest? To answer these questions, we
      reviewed the relevant literature using the standard Prescrire methodology.
      Retrospective studies of several thousand cases suggest that the chances of
      survival depend on how rapidly survival measures are implemented, how quickly
      medical help arrives, the type of cardiac arrhythmia, early defibrillation, and
      return of spontaneous circulation. The chances of survival without neurological
      sequelae are virtually nil when medical assistance does not arrive within 8
      minutes and when the patient is already in asystole. Unless spontaneous
      circulation resumes after 30 minutes of medical resuscitation, the survival
      chances are also considered to be nil, except in case of hypothermia or
      persistent ventricular fibrillation (or tachycardia): it is then reasonable to
      cease resuscitation attempts. However, it may be appropriate to continue
      resuscitation procedures beyond 30 minutes in order to help relatives come to
      terms with the patient's death. In practice, when sudden cardiac arrest occurs in
      the community, those present must implement a chain of survival in order to
      optimise the patient's chances of survival. Physicians called to the scene must
      assess the victim's chances of survival in order to decide when to halt
      resuscitation attempts.

PMID- 21180386
TI  - The French medical sales charter: ineffective.

PMID- 21180385
TI  - Reporting of errors by healthcare professionals.
AB  - The realisation that an error has been committed, and the courage to discuss it
      openly, opens the way to a constructive process to improve one's professional
      practices, in interaction with healthcare organisations. Reporting errors to
      adverse events programmes is influenced by the impact of errors on healthcare
      professionals and their fears about the outcome and disclosure.The low rate of
      spontaneous reporting results from the obstacles encountered by healthcare
      professionals and reflects their attitudes towards their own errors. The way in
      which individuals make errors and handle adverse events reveals a lot about their
      personality and how they view themselves as professionals. It is not easy to
      report errors and it depends on the individuals concerned. Healthcare
      professionals' "reflexivity" (their ability to reflect on their own actions) is
      an integral part of their professional skills; it is an essential resource for
      analysing errors and improving quality of care. Reporting an error to a programme
      such as Prescrire's Preventing the Preventable is a conscious, professional act.
      It is both lucid and responsible, and part of a commitment to improving
      professional practice and skills, at the individual and institutional level.
      Learning from errors in order to prevent them from happening again supports the
      development of a quality and safety culture that should be encouraged among
      healthcare professionals.

PMID- 21180387
TI  - Medical research centres: deceptive press releases.

PMID- 21180388
TI  - Hypertension in adults without diabetes or complications: what is the target
      blood pressure?

PMID- 21180389
TI  - Characterization of Suid herpesvirus 1 field isolates from Argentina.
AB  - The genomic characterization of Suid herpesvirus 1 (SHV-1) isolates from
      Argentina was accomplished by restriction pattern analysis using the BamHI,
      BstEII and XhoI enzymes. Type II genome has been described only once in
      Argentina. This study revealed considerable homogeneity of BamHI endonuclease
      sites in all the strains analyzed, according to the number and size of the
      fragments. No deletion of BamHI fragment #7 among the Argentinean isolates
      suggests that these strains are wild-type. In addition, the main antigenic domain
      of glycoprotein E of all the Argentinean strains, as well as the reference
      strains and sequences available in the GenBank, were characterized. The
      similarity percent oscillated between 99 and 100%.

PMID- 21180390
TI  - HPV detection and genotyping in males from the city of Cordoba, Argentina.
AB  - A wide range of human papillomavirus (HPV) types can infect the anogenital region
      of males. Although there is a vast knowledge on HPV infections in women as well
      as on their association with cervical cancer, the study of HPV infections in
      males is scarce and controversial. The aim of the present work was to detect and
      typify HPV infections of the anogenital region in males and analyze the
      associated risk factors in the population studied. Anogenital samples from 37
      patients (30 of whom were HIV carriers) attending the Infectology Service at the
      Hospital Nacional de Clinicas in C6rdoba, Argentina, were studied. Nine of these
      patients tested HPV-positive and five out of these nine were found to have mixed
      infections, being 18 and 61 the most frequent genotypes. There was a significant
      correlation between the HPV-positive patients and those having an HPV-compatible
      lesion or AIDS. The present work is the first study in the city of Cordoba which
      contributes relevant results to the knowledge of HPV infection and to the
      possible implementation of measures for its prevention.

PMID- 21180392
TI  - Comparing in vitro activity of tigecycline by using the disk diffusion test, the
      manual microdilution method, and the VITEK 2 automated system.
AB  - Tigecycline is a broad spectrum antibiotic having activity against multiresistant
      isolates. In vitro susceptibility testing is difficult to perform with the use of
      traditional microbiological techniques. The aim of this study was to evaluate the
      disk diffusion test with three different Mueller-Hinton agar brands, and the
      Vitek 2 automated system in comparison with the standard broth microdilution
      method against 200 gram-negative isolates (Escherichia coil, Klebsiella
      pneumoniae, Enterobacter cloacae, Serratia marcescens and Acinetobacter
      baumannii). Among Enterobacteriaceae, the Becton Dickinson agar had the lowest
      rate of minor (32.5%) and major errors (3.8%). No very major errors were found.
      For A. baumanni, the rate of minor and major errors was lower. A high rate of
      agreement (94%) was found between the broth microdilution method and the Vitek 2
      system. Our results show that there are important differences between agars used
      for the disk diffusion test, and that Vitek 2 is a valid tool for susceptibility
      testing in clinical laboratories.

PMID- 21180393
TI  - Enterotoxigenic gene profiles of Bacillus cereus and Bacillus megaterium isolates
      recovered from honey.
AB  - One hundred and thirty two Bacillus cereus and 52 Bacillus megaterium isolates
      from honeys were evaluated for the presence of genes encoding enterotoxin HBL,
      enterotoxin-T, cytotoxin K and the NHE complex, respectively. The relationship
      between hemolytic and coagulase activity and its correlation with the presence of
      the four mentioned enterotoxins was determined by principal component analysis
      (PCA). PCA in B. cereus revealed a positive correlation among free coagulase,
      hemolysis and the presence of genes hblA, hblB, hblC, hblD (HBL complex) and bceT
      (enterotoxin-T), but no correlation with the clumping factor (bound coagulase)
      and the presence of sequences of the NHE complex. On the other hand, PCA in B.
      megaterium showed a high positive correlation between coagulase (bound and free)
      and the haemolytic activity but no correlation in relation to the presence of
      genes of the HBL complex, cytotoxin K, enterotoxin T and the NHE complex. To our
      knowledge, this is the first report of the detection of cytotoxin K and of the
      NHE complex genes in B. megaterium. The relationship between the coagulase
      activity and the presence of virulence factors has not been described before in
      the genus Bacillus, being this work the first report of this correlation.
      Interestingly, the presence of the cytK gene was almost independent of the
      presence of the rest of virulence factors herein analyzed both in B. cereus and
      B. megaterium populations. Our results suggest that honey could be a possible
      vehicle for foodborne illness due to the presence of toxigenic B. cereus and B.
      megaterium strains containing different virulence factors.

PMID- 21180394
TI  - Effects of using mixed wine yeast cultures in the production of Chardonnay wines.
AB  - The effect of using mixed cultures of non-Saccharomyces and Saccharomyces
      cerevisiae yeasts in the physicochemical and sensory qualities of the wines were
      analyzed in this study. Based on growth curves, sugar consumption and glycerol
      production in synthetic must, Candida membranifaciens L1805 was selected from a
      group of four Candidas spp. isolates from Chile and Argentina. This yeast was
      subsequently used in combination with S. cerevisiae in Chardonnay must. A
      monoculture of S. cerevisiae was used as control. The wines fermented with mixed
      cultures had lower volatile acidity and ethanol concentration than the control.
      Furthermore, the chromatographic analysis showed that the wines from mixed
      cultures presented differences in the concentration of esters and propanol. These
      characteristics positively influenced the sensory qualities of the wines produced
      with mixed cultures, which was reflected in the preference for these wines by a
      panel of enologists. This study shows that the use of non-Saccharomyces yeasts
      could be a strategy to obtain distinctive wines using the native microorganisms
      from each winemaking area.

PMID- 21180395
TI  - Impact of inappropriate antimicrobial therapy on patients with bacteremia in
      intensive care units and resistance patterns in Latin America.
AB  - Patient care in an intensive care unit (ICU) is associated with an increased risk
      of developing nosocomial infections. Bacteremia is responsible for a great number
      of cases, 23% of which have attributable mortality in developed countries and can
      affect up to 52% of ICU patients. The main cause of mortality is inadequate and
      inappropriate antimicrobial empirical therapy. The incorrect use of
      antimicrobials is a major risk for identifying multidrug resistant
      microorganisms, thereby involving increased morbidity, mortality and costs.
      Implementing several surveillance systems and becoming acquainted with resistance
      patterns represent a valuable tool for identifying, preventing and treating this
      infectious complication. There is paucity of data regarding antimicrobial
      resistance in bacteremic patients in Latin America, and the available data
      reveals a worrying scenario.

PMID- 21180396
TI  - Investigation of wear in manual toothbrushes from different price categories.
AB  - This clinical study examined differences in wear in manual toothbrushes from
      different price categories. 140 volunteers (14 groups of 10) brushed twice daily
      for 2-3 minutes over a period of three or six months using the modified Bass
      technique and seven different toothbrushes (TB) from three price categories. A: 2
      TB for under 1 Euro; B: 2 TB priced between 1 and 2 Euro; C: 3 TB priced at over
      2 Euro. After a period of three or six months the increase in the bristle surface
      field was determined and the brush heads were rated macroscopically, by light
      microscopy and scanning electron microscopy (SEM) (grades 1-4: new, small, clear
      or very clear signs of use). The statistical analysis was performed with the Mann
      Whitney U-test and Error Rates method (p < or = 0.05). All bristle fields showed
      an increase in surface area over the period of use. When examined macroscopically
      and under light microscopy, very little difference was found between three and
      six months of use, or between brushes from the same price category. The clearest
      distinction was found between categories B and C, whereby C was rated worse. In
      SEM it was difficult to separate the findings according to price categories.
      Here, the scores most often awarded were 3 and 4. The results of the three test
      methods differed markedly from one another. Thus no conclusions on the state of
      the bristles can be drawn from a marked increase in bristle field surface area.
      The category B TB tended to perform best.

PMID- 21180391
TI  - Fluoroquinolone-resistant Streptococcus agalactiae isolates from Argentina.
AB  - Fluoroquinolone resistance is a growing problem that has only recently emerged in
      S. agalactiae. Between 2005-2007, WHONET--Argentina network evaluated
      levofloxacin susceptibility in 1128 clinical S. agalactiae isolates, 10 (0.9%) of
      which proved to be resistant. Nine of them had come from 5 hospitals (in Buenos
      Aires City and 4 Argentinean provinces) and recovered from urine (n=7) and
      vaginal screening cultures (n=2). Three strains were also resistant to
      macrolides, lincosamides and B streptogramins due to the ermA gene. All nine
      fluoroquinolone-resistant isolates bore the same two mutations, Ser79Phe in ParC
      and Ser81Leu in GyrA proteins. Genetic relationships were analyzed by Apal-PFGE
      and two clones were determined, A (n=6) and B (n=3). To our knowledge, these are
      the first fluoroquinolone-resistant S. agalactiae isolates detected in Latin
      America.

PMID- 21180397
TI  - Meet the new boss...same as the old boss? Female supervisors and subordinate
      career prospects.
AB  - Whereas prior research has focused on women's access to managerial authority, an
      equally important question is the effect on subordinates' careers when they
      report to a female boss. One line of thought suggests that female bosses act as
      change agents by fostering the careers of female subordinates, whereas the cog in
      the machine perspective suggests that female bosses either willingly or are
      constrained to promote men's careers. Using data from the 2002 National Study of
      the Changing Workforce, analytic models of subordinates' perceived job-related
      support from supervisors and advancement prospects were developed. Results were
      consistent with the cog in the machine perspective in that in contrast to women,
      men received more job-related support and were more optimistic about their
      careers when they reported to a female supervisor. Yet, given the paucity of
      research on this topic, more research (especially longitudinal studies) is needed
      to fully understand how supervisors affect subordinates' careers.

PMID- 21180398
TI  - SPATIAL AND TEMPORAL DIMENSIONS OF NEIGHBORHOOD EFFECTS ON HIGH SCHOOL
      GRADUATION.
AB  - Research into the effects of neighborhood characteristics on children's behavior
      has burgeoned in recent years, but these studies have generally adopted a limited
      conceptualization of the spatial and temporal dimensions of neighborhood effects.
      We use longitudinal data from the Panel Study of Income Dynamics and techniques
      of spatial data analysis to examine how both the socioeconomic characteristics of
      extralocal neighborhoods-neighborhoods surrounding the immediate neighborhood of
      residence-and the duration of exposure to disadvantaged neighborhoods throughout
      the childhood life course influence the likelihood of graduating from high
      school. Among blacks and whites, socioeconomic advantage in the immediate
      neighborhood increases the likelihood of completing high school, but among whites
      higher levels of socioeconomic advantage in extralocal neighborhoods decrease
      high school graduation rates. Extralocal neighborhood advantage suppresses the
      influence of advantage in the immediate neighborhood so that controlling for
      extralocal conditions provides stronger support for the neighborhood effects
      hypothesis than has previously been observed. Exposure to advantaged
      neighborhoods over the childhood life course exerts a stronger effect than point
      in-time measures on high school graduation, and racial differences in exposure to
      advantaged neighbors over the childhood life course help to suppress a net black
      advantage in the likelihood of completing high school.

PMID- 21180399
TI  - Promises and pitfalls in cell replacement therapy for heart failure.
AB  - Symptomatic heart failure is a complex clinical syndrome with a poor prognosis.
      Many efforts have been made to develop new therapeutic strategies to improve
      prognosis associated with heart failure. In this context, different stem cell
      populations for cardiac regenerative therapy have been examined recently. Here we
      discuss the potential strategies for using stem cells in cardiac regenerative
      therapy and the barriers that remain before an effective cell-based cardiac
      regenerative therapy can be employed clinically.

PMID- 21180400
TI  - Engineering the Properties of Metal Nanostructures via Galvanic Replacement
      Reactions.
AB  - In this review, we will bring the reader up to date with recent advances in the
      use of galvanic replacement reactions to engineer highly tunable nanostructures
      for a variety of applications. We will begin by discussing the variety of
      templates that have been used for such reactions and how the structural details
      (e.g., shape, size, and defects, among others) have interesting effects on the
      ultimate product, beyond serving as a simple site for deposition. This will be
      followed by a discussion of how we can manipulate the processes of alloying and
      dealloying to produce novel structures and how the type of precursor affects the
      final properties. Finally, the interesting optical properties of these materials
      and some innovative applications in areas of biomedical engineering and catalysis
      will be discussed, completing our overview of the state of the art in galvanic
      replacement.

PMID- 21180402
TI  - Primary prevention for offspring of parents with mental illness.

PMID- 21180401
TI  - Electrothermal Fluid Manipulation of High-Conductivity Samples for Laboratory
      Automation Applications.
AB  - Electrothermal flow is a promising technique in microfluidic manipulation toward
      laboratory automation applications, such as clinical diagnostics and high
      throughput drug screening. Despite the potential of electrothermal flow in
      biomedical applications, relative little is known about electrothermal
      manipulation of highly conductive samples, such as physiological fluids and
      buffer solutions. In this study, the characteristics and challenges of
      electrothermal manipulation of fluid samples with different conductivities were
      investigated systematically. Electrothermal flow was shown to create fluid motion
      for samples with a wide range of conductivity when the driving frequency was
      above 100 kHz. For samples with low conductivities (below 1 S/m), the
      characteristics of the electrothermal fluid motions were in quantitative
      agreement with the theory. For samples with high conductivities (above 1 S/m),
      the fluid motion appeared to deviate from the model as a result of potential
      electrochemical reactions and other electrothermal effects. These effects should
      be taken into consideration for electrothermal manipulation of biological samples
      with high conductivities. This study will provide insights in designing
      microfluidic devices for electrokinetic manipulation of biological samples toward
      laboratory automation applications in the future.

PMID- 21180403
TI  - Coercion in psychiatric care: Global and Indian perspective.

PMID- 21180404
TI  - Deprivation, discrimination, human rights violation, and mental health of the
      deprived.

PMID- 21180405
TI  - Fourth revolution in psychiatry - Addressing comorbidity with chronic physical
      disorders.
AB  - The moral treatment of mental patients, Electro Convulsive therapy (ECT), and
      Psychotropic medications constitute the first, second, and third revolution in
      psychiatry, respectively. Addressing comorbidities of mental illnesses with
      chronic physical illnesses will be the fourth revolution in psychiatry. Mind and
      body are inseparable; there is a bidirectional relationship between psyche and
      soma, each influencing the other. Plausible biochemical explanations are
      appearing at an astonishing rate. Psychiatric comorbidity with many chronic
      physical disorders has remained neglected. Such comorbidity with cardiac,
      respiratory, Gastrointestinal, endocrinal, and neurological disorders, trauma,
      and other conditions like HIV and so on, needs to be addressed too. Evidence base
      of prevalence and causal relationship of psychiatric comorbidities in these
      disorders has been highlighted and strategies to meet the challenge of
      comorbidity have been indicated.

PMID- 21180406
TI  - Evidence of altered DNA integrity in the brain regions of suicidal victims of
      Bipolar Depression.
AB  - Deoxyribonucleic acid (DNA) integrity plays a significant role in cell function.
      There are limited studies with regard to the role of DNA damage in bipolar
      affective disorder (BP). In the present study, we have assessed DNA integrity,
      conformation, and stability in the brain region of bipolar depression (BD)
      patients (n=10) compared to age-matched controls (n=8). Genomic DNA was isolated
      from 10 postmortem BD patients' brain regions (frontal cortex, Pons, medulla,
      thalamus, cerebellum, hypothalamus, Parietal, temporal, occipital lobe, and
      hippocampus) and from the age-matched control subjects. DNA from the frontal
      cortex, pons, medulla, and thalamus showed significantly higher number of strand
      breaks in BD (P<0.01) compared to the age-matched controls. However, DNA from the
      hippocampus region was intact and did not show any strand breaks. The stability
      studies also indicated that the melting temperature and ethidium bromide binding
      pattern were altered in the DNA of BD patients' brain regions, except in the
      hippocampus. The conformation studies showed B-A or secondary B-DNA conformation
      (instead of the normal B-DNA) in BD patients' brain regions, with the exception
      of the hippocampus. The levels of redox metals such as Copper (Cu) and Iron (Fe)
      were significantly elevated in the brain regions of the sufferers of BD, while
      the Zinc (Zn) level was decreased. In the hippocampus, there was no change in the
      Fe or Cu levels, whereas, the Zn level was elevated. There was a clear
      correlation between Cu and Fe levels versus strand breaks in the brain regions of
      the BD. To date, as far as we are aware, this is a new comprehensive database on
      stability and conformations of DNA in different brain regions of patients
      affected with BD. The biological significance of these findings is discussed
      here.

PMID- 21180407
TI  - Clinical correlates of thalamus volume deficits in anti-psychotic-naive
      schizophrenia patients: A 3-Tesla MRI study.
AB  - BACKGROUND: Thalamus, the sensory and motor gateway to the cortex, plays an
      important role in cognitive and perceptual disturbances in schizophrenia. Studies
      examining the volume of the thalamus in schizophrenia have reported conflicting
      findings due to the presence of potential confounding factors such as low
      resolution imaging and anti-psychotics. The thalamus volume in anti-psychotic
      naive patients determined using high-resolution 3-Tesla magnetic resonance
      imaging (MRI) has not yet been examined. MATERIALS AND METHODS: Using 3-Tesla
      MRI, this study for the first time examined anti-psychotic-naive schizophrenia
      patients (n=18; M:F:11:7) in comparison with healthy controls (n=19;M:F:9:10)
      group-matched for age, sex, handedness, education, and socioeconomic status. The
      volume of the thalamus was measured using a three-dimensional, interactive, semi
      automated analysis with good inter-rater and intra-rater reliability.
      Psychopathology was assessed using the Scale for Assessment of Negative Symptoms
      (SANS) and the Scale for Assessment of Positive Symptoms (SAPS). RESULTS: Right,
      left, and total thalamus volumes of patients were significantly smaller than
      those of controls after controlling for the potential confounding effect of
      intracranial volume. Thalamus volumes had significant positive correlation with
      positive symptoms score (SAPS) and significant negative correlation with negative
      symptoms score (SANS). CONCLUSIONS: Thalamus volume deficits in anti-psychotic
      naive schizophrenia patients support a neurodevelopmental pathogenesis. The
      contrasting correlation of thalamus volume deficits with psychopathology scores
      suggests that contrasting pruning aberrations underlie symptom genesis in
      schizophrenia.

PMID- 21180408
TI  - Cannabis dependence: Effects of cannabis consumption on inter-regional cerebral
      metabolic relationships in an Indian population.
AB  - BACKGROUND: The effects of cannabis consumption on neurophysiological function
      have been a matter of considerable debate. With the legalization of medical
      marijuana, understanding the consequences of cannabis dependence has become
      extremely important. AIM: We attempted to understand the influence of cannabis on
      cerebral glucose metabolism in certain predetermined regions of interest (ROIs).
      Furthermore, we also explored inter-regional metabolic relationships between ROIs
      forming the "addiction" and "cognitive dysmetria" circuit. MATERIALS AND METHODS:
      2-fluoro, 2-deoxy-glucose positron emission tomography (FDG PET) scans were
      carried out in 16 male patients (age: 25.3+/-10.38 years) with cannabis
      dependence, 8-12 hours after the last cannabis consumption. Resting glucose
      uptake in 14 pre-determined ROIs was compared with glucose uptake in 16 non-drug
      using volunteers (age: 29.2+/-8.39 years). RESULTS: The two groups differed in
      their lateral and medial temporal glucose uptakes by approximately 16-24%. The
      relationships between inter-regional glucose uptakes in the two circuits were
      compared using the Chow Test. Significant differences in inter-regional
      correlations in the medial temporo-frontal and parieto-thalamic were noted
      between the two groups. CONCLUSION: The altered metabolic relationships among
      various brain regions can have potentially important implications for
      understanding cannabis dependence and cannabis-induced psychopathology.

PMID- 21180409
TI  - Severity of alcoholism in Indian males: Correlation with age of onset and family
      history of alcoholism.
AB  - BACKGROUND: Family History of Alcoholism and earlier Age of Onset are found to
      predict Severity of alcoholism. Previous Indian studies in this regard have
      methodological issues related to the definition of alcoholism and reliability of
      information obtained. AIMS: To study the relationship between the Age of
      onset/Family History and Severity of alcoholism. SETTINGS AND DESIGN:
      Consecutively admitted, 20 to 50 year old men, with alcohol-related problems at
      an urban teaching hospital, were recruited. MATERIALS AND METHODS: After
      detoxification, alcohol use detection inventory test, severity of alcohol
      dependence questionnaire, schedule for clinical assessment in neuropsychiatry,
      and family interview for genetic studies were administered. Family history
      density was computed. STATISTICS: Pearson's correlations, linear regression, and
      ANOVA tests were used. RESULTS: Family history density and severity of alcoholism
      were positively correlated. Age of onset of initiation had a significant negative
      correlation with severity. The effect of family history on the rapidity of
      development of Problem-drinking did not reach statistical significance among
      those with early age of onset. The variance explained by the 'family history
      status' and 'age of onset' for the severity of alcoholism was similar to that
      reported in earlier western studies. CONCLUSION: This study, with enhanced
      methodology, using a general hospital sample of problem drinkers concludes that
      the age of onset of initiation is a better predictor of severity of alcoholism,
      than family history of alcoholism alone. Postponing the use of alcohol till the
      age of 25 years could be explored as a primary prevention strategy in genetically
      vulnerable adolescents.

PMID- 21180410
TI  - Pattern of buprenorphine abuse among opioid abusers in Nepal.
AB  - BACKGROUND: Although buprenorphine abusers are a common clinical entity,
      literature on them is rare in Nepal. AIM: To assess whether injectable opioid
      abusers are any different a subgroup vis-a-vis brown sugar abusers in relation to
      their demographic and clinical profiles. MATERIALS AND METHODS: Seventy-six
      opioid abusers, who were admitted over a period of one year, in our de-addiction
      center, were included in the present study. They were divided into two groups
      based on the history of the presence or absence of buprenorphine injection abuse
      in them. The demographic and clinical profiles of these two groups were studied
      and compared. RESULTS: The most characteristic opioid abuse pattern was the abuse
      of brown sugar through inhalation (chasing). A total of 32 (42.1%) among them had
      a history of injectable drug abuse (IDU). Most characteristic buprenorphine abuse
      pattern seen was an evolution from injectable buprenorphine to triple injection
      to brown sugar abuse (Reverse Transition). Injection buprenorphine abusers, who
      attended our clinic, were older in age and had a history of a longer duration of
      abuse than their counterparts who abused opioid drugs through the inhalational
      route only. Their lifetime diagnosis revealed a polysubstance abuse pattern. They
      were more unstable, impulsive, and disorganized in their behavior pattern,
      suggestive of the presence of inadequate personality traits. There were high
      instances of injection-related side effects in the form of the presence of
      thrombophlebitis, HIV positivity, and clinical AIDS in them. CONCLUSION: Findings
      of the current research indicate the presence of a subgroup of patient population
      among opioid abusers with a history of injectable buprenorphine abuse, with
      characteristic personality traits, pattern of drug abuse, and associated physical
      complications resulting from it.

PMID- 21180411
TI  - Validation of the Geriatric Depression Scale for an elderly Sri Lankan clinic
      population.
AB  - BACKGROUND: Geriatric Depression Scale (GDS) has not been validated for the
      elderly population in Sri Lanka. AIM: To translate, validate, and examine the
      effectiveness of GDS and to suggest the optimal cut-off scores for elderly Sri
      Lankans attending a psychogeriatric clinic. MATERIALS AND METHODS: The Sinhalese
      translation of GDS (GDS-S) was administered to people aged 55 years and above,
      attending a psychogeriatric outpatient clinic. The diagnostic performance of the
      instrument was compared against the ICD 10 diagnosis of a consultant
      psychiatrist, which was considered the 'gold standard'. Receiver operating
      characteristic (ROC) analysis was carried out to compare the diagnostic
      performance of the GDS-S. Optimal cut-off scores for depression and sensitivity
      and the specificity of the instrument was determined. RESULTS: A total of 60
      subjects formed the final sample (male/female=16/44) of which 30 were depressed,
      while 30 were age- and sex-matched controls. The optimal cut-off score for GDS-S
      was 8 for differentiating non-depressed from mildly depressed, while the cut-off
      score for moderate depression was 10. Sensitivity and specificity of GDS-S was
      73.3% for differentiating depressed from non-depressed. CONCLUSION: GDS is
      culturally acceptable, easy to use, sensitive, and a valid instrument to diagnose
      depression and to differentiate mild from moderate depression in an elderly Sri
      Lankan clinic population.

PMID- 21180412
TI  - Anti-psychotic prescription pattern: A preliminary survey of Psychiatrists in
      India.
AB  - Although anti-psychotic medications are available in India since a long time,
      little is known about the prescription patterns of Indian psychiatrists. An email
      survey was sent to 1100 psychiatrists, of which 168 responded. The three most
      commonly prescribed anti-psychotics were risperidone, olanzapine, and
      haloperidol. It was also found that typical anti-psychotics comprise of 25.15%
      (SD=21.66; range 0-100) of all prescriptions and in about 22.36% of the cases the
      psychiatrists were using more than one anti-psychotic in the same patient.

PMID- 21180413
TI  - Familial vulnerability to an unusual cognitive adverse effect of topiramate:
      Discussion of mechanisms.
AB  - BACKGROUND: Some patients experience cognitive disturbances with topiramate. CASE
      HISTORIES: A 19-year-old bipolar woman and her 46-year-old mother with paranoid
      personality disorder both used topiramate (25-50 mg/day) off-label for weight
      loss. Both women suffer from learning disorders, and both are excessively
      sensitive to the sedative adverse effects of psychotropic medications. RESULTS:
      Within days of starting topiramate, the women began to exhibit troublesome word-
      and phrase-repetition and word substitution, both occurring only in their written
      expression. The symptoms were associated with mild sedation, persisted during two
      weeks of topiramate treatment, and remitted days after topiramate was withdrawn.
      DISCUSSION: The presence of the learning disorders and the sensitivity to the
      sedative adverse effects of drugs may explain why cognitive adverse effects,
      known to occur with topiramate, developed at the low dose of 25-50 mg/day. The
      proclivity of topiramate to affect language functions and a possible familial
      vulnerability herein may explain why the women explained similar, language
      specific symptoms. An investigation of topiramate-induced cognitive impairments
      in family members with epilepsy may throw light on the subject.

PMID- 21180414
TI  - Resolution of symptoms in neuroleptic malignant syndrome.
AB  - Although neuroleptic malignant syndrome (NMS) manifests consistently with
      hyperthermia, muscle rigidity, altered mental state, and autonomic instability,
      heterogeneity exists in the onset, initial manifestations, course, laboratory
      findings, response to treatment, and pattern of resolution. Comorbid physical
      conditions tend to confuse the picture. We report a case of NMS with such a
      presentation.

PMID- 21180415
TI  - Treatment of severe borderline personality disorder with clozapine.
AB  - Patients with borderline personality disorder (BPD) show significant impairment
      in the domain of interpersonal and social functioning and may use the resources
      of health and social services extensively, with little beneficial outcome. At
      present there are no clear guidelines in literature for the use of
      pharmacotherapy in the management of BPD. According to the scanty literature
      available in the form of case reports and small studies, clozapine has been
      demonstrated to be effective in the management of BPD. The case presented here
      describes the effectiveness of clozapine in a young female patient with severe
      BPD (without psychotic features), who had repeated and prolonged periods of
      hospitalization and was successfully treated with a moderate dose of clozapine,
      following a failure to improve with other psychotropic medications. More studies
      are suggested to evaluate the efficacy of clozapine in patients with BPD, both
      with and without psychotic features, to find out the optimum dose and to weigh
      the risk and benefits of clozapine.

PMID- 21180417
TI  - Dose calculation with brief-pulse ECT demystified.

PMID- 21180416
TI  - Relevance of psychiatry in dermatology: Present concepts.
AB  - Skin is an organ that has a primary function in tactile receptivity and reacts
      directly upon emotional stimuli. Dermatological practice involves a psychosomatic
      dimension. A relationship between psychological factors and skin diseases has
      long been hypothesized. Psychodermatology addresses the interaction between mind
      and skin. It is divided into three categories according to the relationship
      between skin diseases and mental disorders. This article reviews different
      dermatological conditions under each of the three categories namely psychosomatic
      disorders, dermatological conditions due to primary and secondary psychiatric
      disorders. Dermatological conditions resulting from psychiatric conditions like
      stress/depression and those caused by psychiatric disorders are discussed. This
      review intends to present the relationship between the 'skin' and the 'mind'
      specifically from the dermatology point of view. The effects on the quality of
      life as a result of psychodermatological conditions are highlighted. A
      multidisciplinary approach for treatment from both dermatologic and psychiatric
      viewpoints are suggested.

PMID- 21180418
TI  - Cognitive impairment and symptoms of depression among geriatric patients in a
      tertiary care unit in Sri Lanka.

PMID- 21180419
TI  - Anti-psychotic drug prescription pattern for schizophrenia: Observation from a
      general hospital psychiatry unit.

PMID- 21180420
TI  - Why do mentally ill patients seek religious places for treatment?

PMID- 21180421
TI  - Psychological support for fathers of artificial insemination donor children.

PMID- 21180422
TI  - Creativity, psychosis and human evolution: The exemplar case of neuregulin 1
      gene.

PMID- 21180423
TI  - Facets of morbid jealousy: With an anecdote from a historical Tamil romance.
AB  - Morbid jealousy is a symptom which occurs in many psychiatric conditions. The
      complex emotional aspects of jealousy have been discussed by earlier authors. The
      clinical, cultural, social, and forensic aspects, are touched upon. Morbid
      jealousy is a favourite topic among novelists and dramatists. "Othello" is a
      classic example. This topic is covered in one of the famous historical romances
      of the Tamil author, Kalki.

PMID- 21180424
TI  - Anxiety disorders in ancient Indian literature.
AB  - In western literature, the oldest description of symptoms of PTSD, an anxiety
      group of disorder, is seen in Homer's Iliad written around 720 BC. According to
      Shay, Achilles was suffering from symptoms of PTSD. However, in the Indian
      literature it was mentioned around 5000 BC. The description of a PTSD-like
      syndrome is seen in the Ramayana, although it was not described as PTSD or by any
      other similar name. Ravana's brother Marrich was having symptoms of PTSD after he
      was grievously hurt by Lord Rama's arrow and was almost dead. This traumatic
      event threatened his physical integrity. He developed all the symptoms of PTSD,
      like hyper-arousal, re-experiencing the events and avoidance. He also gave up his
      natural work of harassing the monk and got engaged in meditation and austerities.
      His symptoms lasted for many years till Lord Rama killed him, while he was
      masquerading as a golden deer to deceive Sita. In another ancient epic Shrimad
      Bhagavatam, Maharshi Ved Vyasa described the symptoms of Generalized Anxiety
      Disorder (GAD). The demon King Kansha developed GAD-like symptoms, when Lord
      Krishna killed all his demons and threatened to kill him. He developed symptoms
      of GAD, like excessive worry about the attack from his arch foe Krishna,
      difficulty in concentration and difficulty in falling asleep. Like Marrich, the
      symptoms of Kansha also lasted until Lord Krishna killed him.

PMID- 21180425
TI  - Childhood Visual Impairment and other Challenges in the Middle East and African
      Region.

PMID- 21180426
TI  - Ab interno trabeculectomy.
AB  - Anterior chamber drainage angle surgery, namely trabeculotomy and goniotomy, has
      been commonly utilized in children for many years. Its' reported success has
      ranged between 68% and 100% in infants and young children with congenital
      glaucoma. However, the long-term success of these procedures has been limited in
      adults presumably due to the formation of anterior synechiae (AS) in the
      postoperative phase. Recently, ab interno trabeculectomy with the TrabectomeTM
      has emerged as a novel surgical approach to effectively and selectively remove
      and ablate the trabecular meshwork and the inner wall of the Schlemm's canal in
      an attempt to avoid AS formation or other forms of wound healing with resultant
      closure of the cleft. This procedure seems to have an appealing safety profile
      with respect to early hypotony or infection if compared to trabeculectomy or
      glaucoma drainage device implantation. This might be advantageous in some of the
      impoverish regions of the Middle East and Africa where patients experience
      difficulties keeping up with their postoperative visits. It is important to note
      that no randomized trial comparing the Trabectome to other glaucoma procedures
      appears to have been published to date. Trabectome surgery is not a panacea,
      however, and it is associated with early postoperative intraocular pressure
      spikes that may require additional glaucoma surgery as well as a high incidence
      of hyphema. Reported results show that postoperative intraocular pressure (IOP)
      remains, at best, in the mid-teen range making it undesirable in patients with
      low-target IOP goals. A major advantage of Trabectome surgery is that it does not
      preclude further glaucoma surgery involving the conjunctiva, such as a
      trabeculectomy or drainage device implantation. As prospective randomized long
      term clinical data become available, we will be better positioned to elucidate
      the exact role of this technique in the glaucoma surgical armamentarium.

PMID- 21180427
TI  - Adalimumab (humiraTM) in ophthalmology: a review of the literature.
AB  - Tumor Necrosis Factor alpha (TNF-alpha) is a pleiotropic cytokine which plays a
      primary role in the induction of inflammation in autoimmune diseases. The newest
      anti-TNF-alpha agent is adalimumab (Humira, Abbott Pharmaceutical Inc.), a human
      derived antibody. This review summarizes the characteristics of adalimumab,
      highlighting its clinical use in systemic and ocular inflammatory disorders, and
      the possible therapeutic strategies. Adalimumab has been successfully used for
      the treatment of rheumatoid arthritis, ankylosing spondylitis, and psoriasis
      arthritis. More recently, adalimumab has shown promising qualities in controlling
      intraocular inflammations, even though this has been used prevalently as a rescue
      therapy for unresponsive cases. This biologic agent was also used in pediatric
      cases, showing a good safety and efficacy profile. Albeit no direct comparison
      with other biologics has been done, and adalimumab seems to be equivalent to the
      other anti-TNF-alpha, the switching to adalimumab can offer a better uveitic
      control. Adalimumab is a promising drug for the treatment of uveitis, even though
      further studies are needed on its application as a primary therapy in uveitis.

PMID- 21180428
TI  - Refractive error and visual functions in children with special needs compared
      with the first grade school students in oman.
AB  - BACKGROUND: We evaluated the refractive status and visual function of children
      with special needs (other handicap) in 2010 and compared them with healthy 1(st)
      grade school students in Oman. MATERIALS AND METHODS: This was a cohort study.
      Optometrists recorded vision using a logarithm of minimum angle of resolution
      (LogMAR) chart. Preferential looking method was used for testing 31 children.
      Cycloplegic refraction was performed on all children. Contrast sensitivity was
      tested using 2.5%, 10%, and 100% contrast charts. Ocular movement, alignment, and
      anterior segment were also assessed. A pediatrician reviewed the health records
      of all the children at the time of their enrollment in this study to determine if
      the child had been diagnosed with a systemic condition or syndromes. The visual
      functions were assessed by study investigators. We estimated the rates and the
      risk of different visual function defects in children with special needs. RESULT:
      The prevalence of refractive error in 70 children (4.7 +/- 0.8 years) with
      special needs (group 1) and 175 normal healthy first grade students (group 2)
      were 58.5% and 2.9%, respectively. The risk of refractive error was significantly
      higher in children with special needs [relative risk, 48.1 (95% confidence
      interval, 17.54-131.8)]. Hyperopia (>1.00 D), myopia (>= 1.00D) and astigmatism
      (>= +/-1.00 D) were found in 18.6%, 24.3%, and 27.1%, respectively, in group 1.
      Six children in this group had defective near vision. Sixteen (80%) children with
      Down syndrome had refractive error. Seven (50%) children with developmental
      disorder showed decreased contrast sensitivity. CONCLUSION: Prevalence of
      uncorrected refractive error was much higher in children with special needs.
      Prevalence of strabismus, nystagmus, and reduced contrast sensitivity was also
      higher in children with special needs. Early vision screening, visual function
      assessment, correction of refractive error, and frequent follow-up are
      recommended.

PMID- 21180429
TI  - Case-control studies and risk factors for cataract in two population studies in
      Nigeria.
AB  - PURPOSE: The aim of this study was to determine and investigate the risks
      associated with cataract in South Western and North Central Nigeria. MATERIALS
      AND METHODS: A hospital-based, case-control study was conducted in Lagos (Lagos
      group), South Western Nigeria, and Kano (Kano group), North Central Nigeria. In
      this study, 530 subjects with visually impairing cataracts (study group) and 530
      age(-) and sex-matched controls (control group) were recruited from patients aged
      40 to 89 years attending the ophthalmology clinics at the same hospital. All
      subjects were examined for the presence/absence of cataract and interviewed about
      their educational achievements, diarrhea/dehydration crises, urban/rural
      residence, and ophthalmological conditions. A standardized questionnaire was
      administered to all subjects. Logistic regression analysis with age adjustment,
      literacy, outdoor work, body mass index, crowding, regular vegetable intake,
      heavy alcohol, and cigarette intake was performed. P < 0.05 was considered
      statistically significant. RESULTS: Using multivariate regression analysis, after
      adjustment for age and other demographics factors, low education and no education
      [adjusted odds ratios (OR) = 2.42 for the Lagos group and 4.10 for Kano group]
      and a positive history of diarrhea or dehydration crises (adjusted OR = 1.31 for
      the Lagos group and 2.12 for Kano group) were associated with an increased risk
      for cataract. Senile cataracts were more common among the Fulani ethnic group
      (adjusted OR = 2.21) of North Central Nigeria. However, rural or urban residence
      did not reveal any positive risk for cataract. CONCLUSION: The risk of cataract
      in North Central Nigeria is similar to that in South Western Nigeria. Cataracts
      were strongly associated with increasing age, with peak age of 55 years and were
      more common in those with lower education, severe diarrhea and among the members
      of Fulani in North Central Nigeria.

PMID- 21180430
TI  - Perception and attitude of people toward onchocerciasis (river blindness) in
      South Western Nigeria.
AB  - BACKGROUND: Onchocerciasis (river blindness) is a major cause of bilateral
      blindness with devastating socioeconomic consequences. Since Nigeria is the most
      heavily onchocerciasis endemic country in the world, the information on people's
      knowledge about this disease is significant. This could influence their response
      to current preventive measures of the African Programme for Onchocerciasis
      Control. AIM: This study was designed to estimate the level of knowledge and
      attitudes of rural/semi-urban communities in Ife North Local Government Area of
      Osun State toward onchocerciasis. MATERIALS AND METHODS: Cluster random sampling
      was used to select 500 adults for the study. Semi-structured questionnaires were
      administered to subjects. Data on knowledge of the local name, cause, mode of
      transmission, manifestation, severity, treatment, and prevention of
      onchocerciasis were collected and analysed. Statistical analysis included
      frequency distribution of the responses and a Chi-square test for comparison of
      variables with the P value for statistical significance set at 0.05. RESULTS:
      Onchocerciasis was well known by its local name among 458 (91.6%) of the
      respondents. Only seven (1.4%) knew that it affects both the eyes and skin. The
      cause was commonly attributed to impure blood by 114 (22.8%), whereas
      transmission was thought to be through fomites by 161 (32.2%). Only 12 (2.4%)
      respondents attributed the disease to blackfly bites. The level of education and
      the association of onchocerciasis with a river were significantly associated (P =
      0.001). Subcutaneous nodules were felt to contain water (85.4%), baby worms
      (3.2%), and fat (0.6%). There was a negative attitude toward sufferers of the
      disease. CONCLUSION: Adequate information transfer in simple local dialect by
      trained personnel to the communities at risk of onchocerciasis is essential for
      better uptake of all aspects of the onchocerciasis control programme.

PMID- 21180431
TI  - Incidence and complications of traditional eye medications in Nigeria in a
      teaching hospital.
AB  - PURPOSE: The aim of this study was to determine the types and nature of
      traditional eye medications (TEMs), their sources, and the ocular complications
      that may arise from use in a teaching hospital in Nigeria. MATERIALS AND METHODS:
      A prospective study of consecutive subjects who used TEM before presentation to
      the Eye Clinic of the University of Benin Teaching Hospital, Benin City, Nigeria
      between July 1, 2004 and June 30, 2008. P < 0.05 was considered statistically
      significant. RESULTS: A total of 113 subjects were evaluated of which 64 were
      males (56.6%), females (43.4%) were females. There was no significant difference
      in the number of males and females (P > 0.05). Rural dwellers were more likely to
      use TEM than urban dwellers (P < 0.0001). The mean age of the subjects was 47.9
      +/- 22.3 years (range, 4-90 years). The most common traditional medication was
      derived from plant extracts (54.9%) followed by concoctions (21.2%).
      Complications occurred in 54.8% of the subjects. Ocular complications included
      corneal opacities in 13.35% of subjects, staphyloma in 9%, and corneal ulcers in
      8%. Other complications were panophthalmitis, endophthalmitis, uveitis, cataract,
      and bullous keratopathy. Eleven subjects underwent evisceration or enucleation of
      the affected eye. There was no significant difference in the type of medication
      used and ocular complications (P = 0.956). Sources of TEM were self-medication in
      38.9% of subjects, relatives in 27.4%, and traditional healers in 17.7%.
      CONCLUSION: The use of TEM is a common practice that could be harmful and lead to
      blindness. Proper health education of the public and traditional healers can
      reduce the prevalence of preventable blindness.

PMID- 21180432
TI  - Computerized motion sensitivity screening tests in a multicountry rural
      onchocercal community survey in Africa.
AB  - PURPOSE: To determine whether the Wu-Jones Motion Sensitivity Screening Test
      (MSST) accurately reflects the burden of optic nerve disease in several
      onchoendemic communities in Africa. MATERIALS AND METHODS: The MSST was used to
      evaluate subjects in the communities of Raja in Sudan, Bushenyi in Uganda,
      Morogoro in Tanzania, and Ikon, Olomboro, and Gembu in Nigeria. Motion
      sensitivity was expressed as a percentage of motion detected in the individual
      eye, and this was averaged for the community. A perfectly normal eye would detect
      all motion and score 100%. RESULTS: In this study, 3858 eyes of 2072 subjects
      were tested. The test was completed in 76% of respondents. Acceptability was
      high. Average test time was 120.4 s. The overall mean motion sensitivity of all
      eyes tested was 88.49%, +/-17.49. Using a cutoff level of 50%, 6.4% of all
      subjects tested were subnormal. The highest proportion of subnormals recorded was
      in Morogoro at 12.7%. Severe defects in a community best correlated with optic
      nerve disease prevalence, while the proportion of the defect from a higher cutoff
      level best correlated with overall ocular morbidity. A repeat examination in the
      next 5 years following ivermectin treatment will show the influence, if any, on
      community-wide MSST performance. CONCLUSION: A wide range in community scores
      reflected disease diversity. The MSST appears to be a useful test in community
      wide screening and diagnosis as it reflects the general level of ocular pathology
      and specifically, optic nerve disease.

PMID- 21180433
TI  - Ophthalmic manifestations of leukemia in a tertiary hospital population of adult
      nigerian africans.
AB  - PURPOSE: To determine the prevalence and pattern of leukemic ophthalmopathy among
      adults at the University of Nigeria Teaching Hospital (UNTH), Enugu, south
      eastern, Nigeria. MATERIALS AND METHODS: This prospective, observational case
      series surveyed adult leukemia patients presenting at UNTH's departments of
      Hematology/Immunology and Ophthalmology from July 2003 to August 2008. The
      demographic profile, clinical data from for each individual in the cohort were
      statistically collated and analyzed. A P <0.05 was considered as statistically
      significant. RESULTS: There were 72 participants (45 males and 27 females), aged
      32.7 +/- 9.8 years (range, 18 years to 72 years). Leukemic ophthalmopathy was
      present in 77.8% of subjects. The leading ophthalmic manifestations of leukemia
      were retinal vascular abnormalities in 50.0% of subjects, conjunctival pallor in
      27.8% of subjects, sub-conjunctival hemorrhage in 19.4% of subjects, and retinal
      hemorrhage in 16.7% of subjects. Ocular co-morbidity was present in 47.2% of
      subjects. Vision loss occurred in 37.5% of subjects, of which 32.1% was leukemia
      related, and the remaining due to ocular co-morbidity. Leukemic ophthalmopathy
      was more prevalent in chronic leukemia (P <0.05), frequently affected the ocular
      posterior segment (P < 0.05), and often resulted from secondary hematologic
      complications (P <0.05). There was no gender difference in the prevalence of
      leukemia (P = 0.0822) or leukemic ophthalmopathy (P = 0.6624). CONCLUSION: The
      prevalence of leukemic ophthalmopathy in Enugu is high. It is often associated
      with significant ocular co-morbidity and vision loss. These have implications for
      clinicians involved in leukemia management. Early diagnosis and regular
      ophthalmic examinations are recommended to optimize treatment outcomes.

PMID- 21180434
TI  - Tracing children with blindness and visual impairment using the key informant
      survey in a district of north-Western Nigeria.
AB  - PURPOSE: To identify children with irreversible blindness in a district of
      northern Nigeria for enrolment into an inclusive education pilot project.
      MATERIALS AND METHODS: Using key informants (KIs) working and residing within the
      communities, children with blindness and visual impairment in Gwadabawa local
      government area (LGA) were identified and then examined by a team of
      ophthalmologists/optometrists. Data analysis was performed manually using simple
      percentages and proportions. RESULTS: Sixty children were reported with visual
      problems by parents/guardians of whom 58 (97%) were examined. Twenty children
      (35%) were blind, 17 (29%) were irreversibly blind, and 9 (16%) had low vision
      (<6/18 to 3/60) with presenting vision. The major causes of childhood blindness
      were corneal opacity/phthisis bulbi (75%), and cataract (15%). The cause of
      irreversible blindness in these children was largely preventable (80%) as it was
      due to childhood-related illnesses, such as vitamin A deficiency and measles.
      CONCLUSIONS: The major causes of childhood blindness in the study area were
      avoidable and the use of KI survey in this study provided an opportunity for
      service delivery.

PMID- 21180435
TI  - Psychosocial characteristics of totally blind people in a nigerian city.
AB  - PURPOSE: To characterize the demographic and psychosocial problems of a group of
      blind people as a way of attracting more attention to and providing data that can
      improve the psychosocial care of the visually impaired. MATERIALS AND METHOD: A
      cross-sectional descriptive study of a population of totally blind people in
      Ilorin, Nigeria using a self-report questionnaire (SRQ). The questionnaire was
      verbally administered by the study personnel in the local language. Simple
      frequency tables were obtained and the Chi-square test was performed to determine
      significant differences between variables. P value <0.05 was considered
      statistically significant. RESULTS: Sixty one blind patients consented to
      participate. Most participants were engaged in street begging for their
      livelihood. Most subjects desired a job change, signifying dissatisfaction with
      the present occupation. Up to 80% of the cohort was married and had spouses who
      were also blind in at least one eye. Approximately two-thirds had five or more
      children and majority lived with family members who were responsible for taking
      care of their personal hygiene, cooking and mobility. The majority developed
      blindness in childhood and 16% had a family history of blindness and 77% had
      never used conventional eye care, with corneal disease being the most frequent
      cause of blindness. Many feared that their children may also become blind. Thirty
      one (51%) scored >=5 on SRQ and were classified as probable cases of
      psychological disorder. CONCLUSION: Blindness in a majority of cases that started
      in childhood was probably preventable. Inaccessibility to or failure of the
      formal rehabilitation and social welfare systems may have caused this
      psychosocial dilemma. The high level of social and family interaction provides
      opportunity for organized preventive ophthalmology, community health care
      services and psychosocial care.

PMID- 21180436
TI  - A forecast of ophthalmology practice trends in saudi arabia: a survey of junior
      residents.
AB  - PURPOSE: The aim of this study is to identify the trends in practice pattern
      among current ophthalmology residents in Saudi Arabia. MATERIALS AND METHODS:
      Ophthalmology residents in Saudi Arabia responded anonymously to a written survey
      between November 2007 and February 2008. The survey contained questions on
      demographic information, medical education, residency training, career goals and
      factors influencing their career choice. The data were categorized by gender. The
      influence of gender on outcome was assessed in a univariate fashion using the Chi
      square or Fisher exact test when appropriate. A P-value of 0.05 or less was
      considered statistically significant for all analyses. RESULTS: A total of 68 out
      of 85 residents (80%) responded to the survey. Over one-half of the residents
      preferred to pursue a fellowship within Saudi Arabia (53%), while others (25%)
      planned to train in North America. The majority of respondents wished to practice
      in an urban setting (63%). Anterior segment was the most desired subspecialty,
      while general ophthalmology and glaucoma were not a popular choice. Most
      residents were interested in refractive surgery (77%) and research (75%). The
      main factor influencing the decision to pursue ophthalmology was the ability to
      combine medicine and surgery (97%), while a positive elective experience was also
      an important factor, particularly for female respondents (91% vs. 57%; P <
      0.001). CONCLUSION: Concerted efforts are required to encourage adoption to
      ophthalmic practice in public institutions rather than in private practice. In
      addition training in underrepresented subspecilaties should be encouraged to
      ensure adequate ophthalmic care for all citizens of Saudi Arabia.

PMID- 21180437
TI  - Reasons for not performing keratorefractive surgery in patients seeking
      refractive surgery in a hospital-based cohort in "yemen".
AB  - BACKGROUND: To determine and analyze the reasons why keratorefractive surgery,
      laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) were
      not performed in patients who presented for refractive surgery consultation.
      MATERIALS AND METHODS: A retrospective observational study was performed between
      January 2006 and December 2007 in the Yemen Magrabi Hospital. The case records of
      2,091 consecutive new patients who presented for refractive surgery were
      reviewed. Information from the pre-operative ophthalmic examination, such as
      refractive error, corneal topography and visual acuity, were analyzed. The
      reasons for not performing LASIK and PRK in the cases that were rejected were
      recorded and analyzed. RESULTS: In this cohort, 1,660 (79.4%) patients were
      advised to have LASIK or PRK from the 2,091 patients examined. LASIK and PRK were
      not advised in 431 (21%) patients. The most common reasons for not performing the
      surgery were high myopia >-11.00 Diopters (19%), keratoconus (18%), suboptimal
      central corneal thickness (15%), cataract (12%) and keratoconus suspect (forme
      fruste keratoconus) (10%). CONCLUSION: Patients who requested keratorefractive
      surgery have a variety of problems and warrant comprehensive attention to
      selection criteria on the part of the surgeon. Corneal topographies and
      pachymetry of refractive surgery candidates need to be read cautiously. High
      refractive error, keratoconus and insufficient corneal thickness were found to be
      the leading reasons for not performing keratorefractive surgery in this study.

PMID- 21180438
TI  - The effects of blunt trauma and cataract surgery on corneal endothelial cell
      density.
AB  - PURPOSE: This study was designed to investigate the effects of trauma and
      cataract surgery on corneal endothelial cell density (ECD) in patients with a
      traumatic cataract due to blunt trauma without globe laceration. MATERIALS AND
      METHODS: In this prospective study, 31 subjects with traumatic cataract
      (traumatic cataract group) and 30 subjects with a senile cataract (control group)
      were enrolled. The subjects with traumatic cataract were subdivided into two
      groups: uncomplicated surgery subgroup (n = 19) in which subjects underwent
      standard phacoemulsification with intraocular lens implantation and complicated
      surgery subgroup (n = 12) in which subjects underwent cataract surgery other than
      standard phacoemulsification. The ECD of the traumatic cataract group and the
      control group was compared preoperatively and at 3 months or later
      postoperatively. A P value less than 0.05 was considered statistically
      significant. RESULTS: The ECD in the eyes with traumatic cataract was 13.1% lower
      than that for healthy eyes preoperatively (P = 0.043). Postsurgical ECD decreased
      by 16.7% in complicated surgery subgroup and 11.9% in uncomplicated surgery
      subgroup (P = 0.049) after 3 months postoperatively. The ECD decreased by 10.8%
      in the control group (P = 0.489). CONCLUSIONS: Patients with cataracts due to
      blunt trauma had a decreased endothelial cell count, which was significantly
      aggravated by cataract surgery. The loss of corneal endothelium cells due to
      surgery depends on the surgical approach.

PMID- 21180439
TI  - Combined 23-gauge transconjunctival sutureless vitrectomy and cataract surgery in
      cases with cataract and posterior segment diseases.
AB  - BACKGROUND: Combined cataract surgery and transconjunctival sutureless vitrectomy
      are a good option in patients with cataract and vitreoretinal diseases. AIM: To
      evaluate the effectiveness, outcomes, and complications of combined 23-gauge
      transconjunctival sutureless vitrectomy and cataract surgery. SETTINGS AND
      DESIGN: A retrospective case series was conducted at the Beyoglu Eye Education
      and Research Hospital. MATERIALS AND METHODS: In this study, 28 eyes of 28
      patients underwent combined 23-gauge transconjunctival sutureless vitrectomy and
      phacoemulsification and IOL implantation for cataract and various posterior
      segment diseases. The outcome measures included, visual acuity, intraocular
      pressure changes, and anatomical success were evaluated. RESULTS: The mean follow
      up was 4.8 months (range, 3-15 months). Mean overall preoperative visual acuity
      was 20/333, and final acuity was 20/95 (P < 0.001). Mean intraocular pressure
      (IOP) on the preoperative and first postoperative day was 15.6 +/- 7.5 and 13.8
      +/- 3.3 mmHg, respectively (P > 0.05). Three eyes (10.7%) had postoperative
      hypotony (<6 mmHg)that all recovered spontaneously within the first postoperative
      week. Three eyes (10.7%) required laser treatment for iatrogenic retinal tears.
      Anatomical success was obtained in all cases. No serious complications such as
      endophthalmitis were observed during the follow-up period. CONCLUSION: Combined
      transconjunctival sutureless vitrectomy and phacoemulsification was effective and
      safe in patients with significant lens opacities and vitreoretinal pathology.
      Although the anatomic and visual outcomes were satisfactory, the outcomes
      depended mainly on underlying vitreoretinal pathology.

PMID- 21180440
TI  - Corneal Crosslinking for Keratoconus in Iranian Patients: Outcomes at 1 year
      following treatment.
AB  - AIM AND DESIGN: A retrospective, nonrandomized, single-center clinical study was
      designed to evaluate the outcomes of corneal collagen crosslinking (CXL) for
      progressive keratoconus in Iranian patients 12 months after CXL. SETTINGS: This
      study was carried out at Navid Didegan Eye Center, a private clinic, Mashhad,
      Iran. MATERIALS AND METHODS: Ninety-two eyes of 53 subjects with progressive
      keratoconus were evaluated in this study. All eyes completed 1-year follow-up.
      The outcome measures were uncorrected visual acuity (UCVA), best spectacle
      corrected visual acuity (BSCVA), sphere and cylinder refraction, keratometry, and
      corneal thickness. Comparison of baseline and 1-year postoperative data is
      reported in this study. The Wilcoxon signed-ranked and Student's t-tests were
      used for statistical analyses. P < 0.05 was statistically significant. RESULTS:
      The mean age was 21.5 +/- 3.4 years (range, 16 -30 years). Thirty-one (58.5%) of
      the subjects were men and 22 (41.5%) were women. Mean baseline UCVA and BSCVA
      were 0.61 +/- 0.31 and 0.06 +/- 0.12 logarithm of minimal angle of resolution
      (logMAR), respectively. One year postoperatively UCVA was 0.31 +/- 0.25 logMAR
      and BSCVA was 0.0 +/- 0.01 logMAR. UCVA and BSCVA were statistically higher
      postoperatively (P < 0.001, both parameters). The mean astigmatism decreased by
      0.78 +/- 1.49 diopter (D) with significant variation during the follow-up period
      (P < 0.001). Mean baseline simulated keratometry (SIM K) was 46.94 +/- 2.37 D and
      decreased to 46.0 +/- 2.33 D on year postoperatively (P < 0.001). CONCLUSION:
      Corneal CXL seems to be efficient in stabilization of progressive keratoconus
      progression in Iranian patients at 1 year of followup.

PMID- 21180441
TI  - Mitomycin-C needle bleb revision in congenital glaucoma.
AB  - PURPOSE AND SETTINGS: This study was designed to evaluate the efficacy and safety
      of mitomycin-C (MMC) augmented needling procedure in the management of failed
      bleb after trabeculectomy in congenital glaucoma. This study was carried out at
      Ain Shams University Hospital. PATIENTS AND METHODS: A retrospective study was
      carried on 30 eyes of 25 patients with congenital glaucoma with bleb failure
      after trabeculectomy. The mean age of the subjects was 7.3 +/- 3.4 years (range,
      1-12 years). Under general anesthesia, needling procedure was performed with
      adjunctive use of a mixture of 0.1 mL of MMC (0.04 mg/mL) and 0.2 mL of lidocaine
      1% injected subconjunctivally. Needling was performed with a 30-gauge needle to
      dissect the areas of subconjunctival fibrosis and re-establish aqueous outflow.
      RESULTS: Follow-up ranged from 6 to 20 months (mean, 9.23 +/- 5.25 months). One
      needling revision was performed in 22 eyes (73.3%) and eight eyes (26.7%)
      received two needle revisions. The mean intraocular pressure (IOP) decreased from
      26.9 +/- 2.85 mmHg (range, 21-34 mmHg) before surgery to 15.63 +/- 3.15 mmHg
      (range, 10-24 mmHg) at last follow-up. Complications included significant
      subconjunctival hemorrhage in six eyes, intraoperative bleb leak in two eyes,
      choroidal detachment in one eye, and minimal hyphema in one eye. CONCLUSION: MMC
      needle bleb revision appears to be an effective method to revive failed
      filtration surgery after trabeculectomy in patients with congenital glaucoma.
      This technique is effective in reducing IOP with preservation of the remaining
      conjunctiva for further surgery.

PMID- 21180442
TI  - Malignant nodular hidradenoma of the eyelid: a rare sweat gland tumor.
AB  - We report a case of malignant nodular hidradenoma in a middle-aged man, who
      presented with a nodular swelling in the eyelid. The tumor was similar to its
      benign counterpart but had additional features such as surface ulceration,
      numerous mitiotic figures, and an infiltrative growth pattern. Malignant forms of
      hidradenomas are unusual and the possibility this variant should be considered in
      the differential diagnosis of eyelid tumors.

PMID- 21180443
TI  - Transcorneal tube erosion of an ahmed valve implant in an adult.
AB  - Ahmed valve implants are currently used to manage high-risk complicated adults
      and pediatric glaucoma when standard filtration surgery is unsuccessful. Despite
      its success, the Ahmed valve shunt has significant complications particularly in
      the anterior segment. We report an unusual case of transcorneal tube erosion of
      an Ahmed valve implant in an adult that resulted from long-standing tube-corneal
      touch. Periodic observation of tube position is recommended.

PMID- 21180444
TI  - Progressive posterior lenticonus in a patient with alport syndrome.
AB  - We report a rare case of Alport syndrome with progressive posterior lenticonus. A
      24-year-old male presented to our tertiary eye care center with history of poor
      vision. At initial presentation, the patient had bilateral anterior lenticonus,
      posterior subcapsular cataract, and renal failure. The patient was diagnosed with
      Alport syndrome based on a positive family history of the disease and clinical
      findings. Further examination revealed progressive posterior lenticonus that was
      not present initially. The presence of such finding is important because it
      influences the surgical approach to avoid complications during cataract surgery.

PMID- 21180445
TI  - Acute ocular complications from self-administered topical kermes.
AB  - To report severe ocular complications and their management after self
      administered topical kermes dye eye drops. A case report of a 55-year-old man who
      suffered severe ocular surface damage after application of topical kermes eye
      drops to his left eye. Active compounds of the kermes eye drops were studied for
      their composition. Patient reported decreased vision in the affected eye and the
      external eye examination revealed complete corneal abrasion, cicatrization of the
      conjunctiva, and symblepharon formation. The patient required immediate cleansing
      of the ocular surface along with irrigation. He was treated with topical
      corticosteroids and frequent lubrication. Gas chromatography/mass spectrometry
      analysis of the retrieved topical material revealed the presence of acid. The
      patient's visual acuity improved from 20/200 before treatment to 20/25 after
      treatment. Topically administered kermes eye drops may cause severe ocular
      injuries. Public education, early recognition of such injuries, and timely
      intervention may prevent permanent damage to the ocular adnexae.

PMID- 21180446
TI  - Conjunctival Necrosis due to Subconjunctival Methylprednisolone (Depo-MedrolTM)
      Acetate Injection.
AB  - We report a case of conjunctival necrosis due to subconjunctival
      methylprednisolone (Depo-MedrolTM) acetate injection after phacoemulsification
      surgery. This case report highlights a serious complication of the inadvertent
      use of methylprednisolone as a subconjunctival agent. To report a case of
      conjunctival necrosis due to subconjunctival methylprednisolone (Depo-MedrolTM)
      acetate injection after phacoemulsification. Case report a single case presenting
      to a tertiary ophthalmic unit. An 82-year-old patient underwent uncomplicated
      phacoemulsification in the right eye. Postoperatively, she was given a
      subconjunctival injection of methylprednisolone. Two weeks later, she presented
      with a painful ulcerated lesion of the conjunctiva proximal to the injection
      site. The ulcerated lesion was surgically excised and she made a complete
      recovery. In this reported case, methylprednisolone was used in error with
      significant resultant morbidity. This preparation is not registered for the off
      label use in ophthalmology, and this case report highlights the danger of its
      inadvertent use as a subconjuctival agent.

PMID- 21180447
TI  - Intravitreal avastin for choroidal neovascularization associated with stargardt
      like retinal abnormalities in pseudoxanthoma elasticum.
AB  - The aim of the study was to describe a patient with pseudoxanthoma elasticum
      (PXE), showing Stargardt-like retinal abnormalities, who underwent treatment with
      intravitreal bevacizumab for subfoveal choroidal neovascularization (CNV) of the
      right eye (RE). A 57-year-old woman with diagnosis of angioid streaks, retinal
      flecks, and chorioretinal Stargardt-like atrophy due to PXE was referred to our
      department for sudden decreased vision in her RE (20/160). Upon a complete
      ophthalmologic examination, including fluorescein angiography (FA), and optical
      coherence tomography (OCT), the patient was diagnosed with subfoveal CNV of the
      RE. Owing to the subfoveal localization of the CNV, the patient was submitted to
      intravitreal bevacizumab injection. At the 1-month follow-up, visual acuity (VA)
      improved (20/40), and FA and OCT revealed the CNV closure. Twelve months after
      the treatment, the patient's VA remained stable with no recurrence of active CNV.
      On the basis of our findings, a single intravitreal bevacizumab injection seems
      to induce total regression of CNV complicating PXE, in a patient showing
      Stargardt-like retinal abnormalities. Further investigations are required to
      confirm our results.

PMID- 21180448
TI  - Ophthalmic disorders in adult lymphoma patients.

PMID- 21180449
TI  - Authors' reply.

PMID- 21180450
TI  - Xylene: An overview of its health hazards and preventive measures.
AB  - Xylene is an aromatic hydrocarbon known for its wide usage in tissue processing,
      staining and cover slipping in the histology laboratory. The hazards of xylene
      are well documented, making it a potential occupational hazard for the
      histopathological technicians. As every other profession became cautious of the
      occupational hazards, the very speciality that identifies the illnesses became
      one of the last to become aware and remedy its own hazards. This review article
      aims to discuss the toxicity of xylene and safety measures to counteract the
      hazards and enlists the pros and cons of using various substitutes that claim to
      be much safer, better and faster.

PMID- 21180451
TI  - Kikuchi's disease.
AB  - Kikuchi disease is an idiopathic, generally self-limiting cause for lymphadenitis
      that can be clinically and histologically mistaken for lymphoma or systemic lupus
      erythematosus. Differentiating this disease from common lymphatic disorder is
      extremely important from the pathologist's point of view, which is highlighted in
      the article.

PMID- 21180452
TI  - Glandular odontogenic cyst mimicking central mucoepidermoid carcinoma.
AB  - Glandular odontogenic cyst (GOC) is a rare developmental cyst of the jaws. The
      most common site of occurrence is the anterior mandible, and it is most commonly
      seen in middle-aged people. It is a destructive lesion with a high rate of
      recurrence. A predilection for men is observed. Clinical and radiographic
      findings are not specific, and it can mimic as any other destructive lesion of
      the jaw. The histopathological features of GOC and those of low-grade central
      mucoepidermoid carcinoma (MEC) are similar. Often, they are misdiagnosed as MEC.
      We present a case of GOC in the posterior maxilla, which is a rare site. The
      similarities and differences between GOC and central MEC are also discussed.

PMID- 21180453
TI  - Oral myiasis caused by Chrysomya bezziana.
AB  - Oral myiasis is a rare disease caused by larvae of certain dipteran flies. It is
      mostly reported in developing countries and in the tropics. Herein, a case of
      oral myiasis in the maxillary anterior region of a 14-year-old mentally
      challenged boy is being reported. The myiasis was caused by the larvae of
      Chrysomya bezziana species. The clinical findings are presented. Etiology and the
      importance of oral health in special people are also discussed.

PMID- 21180454
TI  - Odontogenic myxoma of the maxilla: A report of a rare case and review of the
      literature.
AB  - Odontogenic myxoma represents an uncommon benign neoplasm comprising of 3-6% of
      all odontogenic tumors. This article presents a rare case of odontogenic myxoma
      occurring in the maxilla of a 7-year-old male patient with a brief review of the
      pathogenesis, clinical, radiological, histopathological, ultrastructural and
      immunohistochemical characteristics of odontogenic myxoma.

PMID- 21180455
TI  - Adenomatoid odontogenic tumor associated with dentigerous cyst of the maxillary
      antrum: A rare entity.
AB  - Adenomatoid odontogenic tumor (AOT) is an uncommon tumor of odontogenic origin
      composed of odontogenic epithelium in a variety of histoarchitectural patterns.
      Most cases are in females and have a striking tendency to occur in the anterior
      maxilla. However, AOT of the maxillary antrum is extremely rare. A 25-year-old
      female presented with a large radiolucent lesion associated with the crown of an
      unerupted canine located in the maxillary antrum, which was clinically diagnosed
      as dentigerous cyst. The microscopic examination revealed the presence of AOT in
      the fibrous capsule of a dentigerous cyst. Very few cases of AOT associated with
      dentigerous cyst have been reported till date. A case of gigantic AOT that
      occupied the maxillary sinus and associated with dentigerous cyst is described.
      Also, an attempt has been made to determine whether the AOT derived from the
      dentigerous cyst could represent a distinct hybrid variety.

PMID- 21180456
TI  - Melanotic neuroectodermal tumor of infancy: Presentation of a case affecting the
      maxilla.
AB  - Melanotic neuroectodermal tumor of infancy is a rare, distinctive neoplasm of
      early infancy with rapid expansile growth and a high rate of recurrence. Most
      commonly, the lesion affects the maxilla of infants during the first year of
      life. One such case was diagnosed in the Department of Oral Pathology and
      Microbiology in Subharti Dental College, Meerut.

PMID- 21180458
TI  - Journal of pharmacy and bioallied sciences.

PMID- 21180457
TI  - An audit of ranulae occurring with the human immunodeficiency virus infecton.
AB  - Currently, published literature has increasingly projected the ranula as a lesion
      that may be closely associated with exposure to the human immunodeficiency virus
      (HIV). In this report, we document 28 patients who presented with ranulae, among
      whom 19 were HIV infected. In some, this was the only lesion that was the
      sentinel sign of HIV infection. Most probably, this lesion could be considered as
      one of the clinical markers of this infection.

PMID- 21180459
TI  - Introduction to metallic nanoparticles.
AB  - Metallic nanoparticles have fascinated scientist for over a century and are now
      heavily utilized in biomedical sciences and engineering. They are a focus of
      interest because of their huge potential in nanotechnology. Today these materials
      can be synthesized and modified with various chemical functional groups which
      allow them to be conjugated with antibodies, ligands, and drugs of interest and
      thus opening a wide range of potential applications in biotechnology, magnetic
      separation, and preconcentration of target analytes, targeted drug delivery, and
      vehicles for gene and drug delivery and more importantly diagnostic imaging.
      Moreover, various imaging modalities have been developed over the period of time
      such as MRI, CT, PET, ultrasound, SERS, and optical imaging as an aid to image
      various disease states. These imaging modalities differ in both techniques and
      instrumentation and more importantly require a contrast agent with unique
      physiochemical properties. This led to the invention of various nanoparticulated
      contrast agent such as magnetic nanoparticles (Fe(3)O(4)), gold, and silver
      nanoparticles for their application in these imaging modalities. In addition, to
      use various imaging techniques in tandem newer multifunctional nanoshells and
      nanocages have been developed. Thus in this review article, we aim to provide an
      introduction to magnetic nanoparticles (Fe(3)O(4)), gold nanoparticles,
      nanoshells and nanocages, and silver nanoparticles followed by their synthesis,
      physiochemical properties, and citing some recent applications in the diagnostic
      imaging and therapy of cancer.

PMID- 21180460
TI  - Orphan drug: Development trends and strategies.
AB  - The growth of pharma industries has slowed in recent years because of various
      reasons such as patent expiries, generic competition, drying pipelines, and
      increasingly stringent regulatory guidelines. Many blockbuster drugs will loose
      their exclusivity in next 5 years. Therefore, the current economic situation plus
      the huge generic competition shifted the focus of pharmaceutical companies from
      the essential medicines to the new business model - niche busters, also called
      orphan drugs. Orphan drugs may help pharma companies to reduce the impact of
      revenue loss caused by patent expiries of blockbuster drugs. The new business
      model of orphan drugs could offer an integrated healthcare solution that enables
      pharma companies to develop newer areas of therapeutics, diagnosis, treatment,
      monitoring, and patient support. Incentives for drug development provided by
      governments, as well as support from the FDA and EU Commission in special
      protocols, are a further boost for the companies developing orphan drugs.
      Although there may still be challenges ahead for the pharmaceutical industry,
      orphan drugs seem to offer the key to recovery and stability within the market.
      In our study, we have compared the policies and orphan drug incentives worldwide
      alongwith the challenges faced by the pharmaceutical companies. Recent
      developments are seen in orphan drug approval, the various drugs in orphan drug
      pipeline, and the future prospectives for orphan drugs and diseases.

PMID- 21180461
TI  - Contribution of CNS cells in NeuroAIDS.
AB  - NeuroAIDS is becoming a major health problem among AIDS patients and long-term
      HIV survivors. As per 2009 estimates of UNAIDS report, more than 34 million
      people have been infected with HIV out of which >= 50% show signs and symptoms of
      neuropsychiatric disorders. These disorders affect central nervous system (CNS)
      and peripheral nervous systems (PNS). CNS is one of the most protected organ
      systems in body which is protected by blood-brain barrier (BBB). Not only this,
      most of the cells of CNS are negative for receptors and co-receptors for HIV
      infections. Neurons have been found to be completely nonpermissive for HIV
      infection. These facts suggest that neurotoxicity could be an indirect mechanism
      responsible for neuropsychiatric complications. In this review, we will discuss
      the importance of different cell types of CNS and their contribution toward
      neurotoxicity.

PMID- 21180462
TI  - Food and drug administration's critical path initiative and innovations in drug
      development paradigm: Challenges, progress, and controversies.
AB  - During the last decade, despite increased investment in drug research and
      development related activity, stagnation in new drug discovery has been
      documented. Despite a 70% increase in investment in research and development
      related activities, a 40% fall in launch of new chemical entities was seen during
      1994-2004. A steep rise in the attrition rate of drug development has complicated
      the matter. Rising cost and increased attrition rates proved major barriers to
      investment in higher risk drugs or in therapies for uncommon diseases or diseases
      that predominantly afflict the poor. This prompted Food and Drug Administration
      (FDA) to highlight this problem in a 2004 white paper classified as "Critical
      Path Initiative" (CPI) and to initiate steps to target stagnation and rise in
      attrition rates. Many new drug development projects have started worldwide taking
      cue from CPI; adopting microdosing, adaptive designs and taking advantage of
      newly developed biomarkers under the CPI. This review discusses the various
      strategies adopted under CPI to decrease attrition rate and stagnation of new
      drug development, and the challenges and controversies associated with CPI.

PMID- 21180463
TI  - Emerging fungal infections among children: A review on its clinical
      manifestations, diagnosis, and prevention.
AB  - The incidence of fungal infections is increasing at an alarming rate, presenting
      an enormous challenge to healthcare professionals. This increase is directly
      related to the growing population of immunocompromised individuals especially
      children resulting from changes in medical practice such as the use of intensive
      chemotherapy and immunosuppressive drugs. Although healthy children have strong
      natural immunity against fungal infections, then also fungal infection among
      children are increasing very fast. Virtually not all fungi are pathogenic and
      their infection is opportunistic. Fungi can occur in the form of yeast, mould,
      and dimorph. In children fungi can cause superficial infection, i.e., on skin,
      nails, and hair like oral thrush, candida diaper rash, tinea infections, etc.,
      are various types of superficial fungal infections, subcutaneous fungal infection
      in tissues under the skin and lastly it causes systemic infection in deeper
      tissues. Most superficial and subcutaneous fungal infections are easily diagnosed
      and readily amenable to treatment. Opportunistic fungal infections are those that
      cause diseases exclusively in immunocompromised individuals, e.g., aspergillosis,
      zygomycosis, etc. Systemic infections can be life-threatening and are associated
      with high morbidity and mortality. Because diagnosis is difficult and the
      causative agent is often confirmed only at autopsy, the exact incidence of
      systemic infections is difficult to determine. The most frequently encountered
      pathogens are Candida albicans and Aspergillus spp. But other fungi such as non
      albicans Candida spp. are increasingly important.

PMID- 21180464
TI  - Transdermal drug delivery of labetalol hydrochloride: Feasibility and effect of
      penetration enhancers.
AB  - OBJECTIVES: The objective of this study is to investigate the feasibility of
      transdermal drug delivery of Labetalol Hydrochloride (LHCl) and to study the
      effect of different penetration enhancers on the skin permeability of LHCl.
      METHODS: The permeability experiments were conducted using a horizontal glass
      diffusion cell with a diffusional area of 2.37 cm-(2) on albino rat skin. The
      effect of various penetration enhancers namely turpentine oil, dimethyl formamide
      (DMF), menthol, dimethyl sulfoxide, pine oil, and 2-pyrollidone, and the effect
      of the concentration of drug and enhancer in the donor phase on the skin
      permeability of LHCl was studied. RESULTS: The apparent partition coefficient of
      the drug was found to be 6.95, suggesting it to be a lipophilic drug. The
      preliminary skin permeation studies revealed that the permeation of LHCL through
      albino rat skin was moderate (K(p) = 6.490 * 10(-2) cm hr(-1)) from isotonic
      phosphate buffer of pH 7.4. An appreciable increase in the LHCl permeability
      coefficient was observed on using a co-solvent (ethanol 95%) with the penetration
      enhancers in the donor phase. DMSO (10% v/v) was found to be the most effective
      enhancer for Labetalol hydrochloride (Enhancement Factor = 1.165). An increase in
      the concentration of drug and enhancer in the donor cell accentuated the
      permeability coefficient of LHCl. CONCLUSIONS: It was concluded that LHCl could
      be delivered via the dermal route with the use of 10% DMSO as the penetration
      enhancer.

PMID- 21180465
TI  - Fast dissolving strips: A novel approach for the delivery of verapamil.
AB  - OBJECTIVE: Fast dissolving drug delivery system offers a solution for those
      patients having difficulty in swallowing tablets/capsules etc. Verapamil is a
      calcium channel blocker used as an antianginal, antiarrhythmic, and
      antihypertensive agent with extensive first pass metabolism which results in less
      bioavailability. This work investigated the possibility of developing verapamil
      fast dissolving strips allowing fast, reproducible drug dissolution in the oral
      cavity; thus bypassing first pass metabolism. MATERIALS AND METHODS: The fast
      dissolving strips were prepared by solvent casting technique with the help of
      HPMC E6 and maltodextrin. The strips were evaluated for drug content uniformity,
      film thickness, folding endurance, in vitro disintegration time, in vitro
      dissolution studies, surface pH study, and palatability study. RESULTS: Official
      criteria for evaluation parameters were fulfilled by all formulations.
      Disintegration time showed by formulations was found to be in range of 20.4-28.6
      sec. Based on the evaluation parameters, the formulation containing 2% HPMC E6
      and 3.5% maltodextrin showed optimum performance against other formulations.
      CONCLUSION: It was concluded that the fast dissolving strips of verapamil can be
      made by solvent casting technique with enhanced dissolution rate, taste masking,
      and hence better patient compliance and effective therapy.

PMID- 21180466
TI  - Neuropharmacological safety evaluation of jigrine: A polyherbal hepatoprotective
      formulation.
AB  - OBJECTIVE: Jigrine is a herbal hepatoprotective formulation containing aqueous
      extracts of 14 medicinal plants. Present study was designed to evaluate per se
      neuropharmacological effects of jigrine in mice. MATERIALS AND METHODS: Jigrine
      was evaluated in a number of pharmacological test paradigms, viz. open field
      arena, actophotometer, hole board, rotarod, traction test, grip strength test,
      spontaneous alternation behavior, passive avoidance task, and phenobarbital
      sleeping time. RESULTS AND CONCLUSIONS: Jigrine pretreatment (1 and 2 ml/kg,
      p.o.) did not produce any significant effect as compared to normal saline treated
      animals and was found to be free from any acute undesirable central effects at
      these two dose levels.

PMID- 21180468
TI  - Assessment of asthma and chronic obstructive pulmonary disorder in relation to
      reversibility, IgE, eosinophil, and neutrophil count in a University Teaching
      Hospital in South Delhi, India.
AB  - OBJECTIVES: The physiological and clinical similarities between asthma and
      chronic obstructive pulmonary disorder (COPD) make their differentiation
      difficult. In the present study, we compared reversibility to bronchodilator,
      immunoglobulin E (IgE), blood eosinophil and neutrophil levels among asthma and
      COPD patients to differentiate these diseases. MATERIALS AND METHODS: The study
      was carried on 20 asthmatics and 29 patients of COPD that reported to the
      outpatient and inpatient department in University Teaching Hospital, Jamia
      Hamdard, New Delhi, India. The parameters evaluated included pulmonary function
      (FEV(1), FVC, and FEV(1)/FVC), IgE levels, and eosinophil and neutrophil count.
      RESULTS: It was observed that reversibility was significantly higher in asthmatic
      patients, while irreversibility predominates in COPD patients. There was no
      significant difference in pre- and post-FEV(1) and pre- and post-FVC and in their
      percentage predicted. However the percentage change in FEV(1) significantly
      varies in asthma and COPD patients. No significant changes in neutrophil and
      eosinophil levels were observed in these patients. The serum IgE levels were
      found significantly higher in asthmatic patients. CONCLUSIONS: We conclude that
      reversibility in FEV(1) levels or percentage change in FEV(1) and serum IgE
      levels are promising lab parameter to distinguish these two conditions. However,
      further research is required to fully understand the role of neutrophil and
      eosinophil in the onset and development of asthma and COPD.

PMID- 21180467
TI  - A pharmacovigilance study on patients of bronchial asthma in a teaching hospital.
AB  - OBJECTIVE: The present study was conducted to monitor adverse drug reactions in
      patients of bronchial asthma in outpatient department and inpatient department of
      a university teaching hospital in South Delhi. MATERIALS AND METHODS: About 200
      patients irrespective of age and sex with established asthma were interviewed
      during the time period of January 2006 to April 2006 using structured
      questionnaire. Naranjo's adverse drug reaction probability scale was used to
      assess the adverse drug reactions. RESULTS: A total of 15 adverse drug reactions
      were reported in 13 out of 200 asthmatic patients. Among the 13 patients reported
      with adverse drug reactions, 5 (38.5%) were male and 8 (61.5%) patients were
      female. Maximum percentage of ADRs (2 in 15 prescriptions, 13.3%) observed with
      montelukast, followed by beclomethasone (1 in 12 prescriptions, 8.3%), salbutamol
      (6 in 109 prescriptions, 5.5%), and ipratropium (3 in 63 prescriptions, 4.8%).
      CONCLUSIONS: Montelukast was found to be associated with greater percentage of
      adverse drug reactions as compared to other antiasthamatics. The above findings
      are constrained by a small sample size and need to be corroborated by conducting
      long-term studies using a larger sample size.

PMID- 21180469
TI  - Hepatoprotective potential of Decalepis hamiltonii (Wight and Arn) against carbon
      tetrachloride-induced hepatic damage in rats.
AB  - Hepatoprotective activity of the roots of Decalepis hamiltonii (Wight and Arn)
      was studied using carbon tetrachloride (CCl(4)) induced liver injury model in
      albino rats. The hepatotoxicity produced by acute CCl(4) administration was found
      to be inhibited by pretreating the rats with crude methanolic extract of the
      roots of D. hamiltonii (Dh) prior to CCl(4) induction. Hepatotoxic inhibition was
      measured with the decreased levels of hepatic serum marker enzymes (glutamate
      pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT), alkaline
      phosphatase (ALP), and lactate dehydrogenase (LDH) and lipid peroxide formation.
      Imbalance level of glutathione (GSH) and antioxidant enzymes such as catalase,
      glutathione peroxidase, and glutathione reductase were normalized in rats
      pretreated with Dh extract followed by CCl(4) administration. Pathological
      changes of hepatic lesions caused by CCl(4) were also improved by pretreatment
      with the Dh root extract. The results of this study indicate that roots of D.
      hamiltonii could afford a significant protective action in the alleviation of
      CCl(4)-induced hepatic damage in rats.

PMID- 21180470
TI  - Evaluation of immunomodulatory potential of ethanolic extract of Roscoea procera
      rhizomes in mice.
AB  - PURPOSE: The aim of present study was to evaluate immunomodulatory potential of
      ethanolic extract of Roscoea procera (Zingiberaceae) rhizomes by using delayed
      type hypersensitivity (DTH) and carbon clearance method in comparison to standard
      established immunosuppressant drug, cyclophosphamide (30 mg/kg, i.p.) in mice.
      MATERIAL AND METHODS: The extract was comprised to acute toxicity (OECD-423
      guideline), DTH and carbon clearance method for their immunomodulatory potential.
      Ethanolic extract of Roscoea procera rhizomes administered orally at doses 300
      mg/kg and 600 mg/kg, p.o. to mice. RESULT AND CONCLUSION: Result of our study
      revealed that, the foot pat thickness of ethanolic extract group (P<0.05)
      significantly enhanced the production of circulating antibody titre in response
      to Sheep red blood cells (SRBC) and phagocytic functions of mononuclear
      macrophages and non-specific immunity. Result were also supported by serological
      and haematological tests data. Hence, the present investigation reveals that,
      ethanolic extract of Roscoea procera rhizomes possesses immunostimulant
      properties. Further studies to identify the active moieties and elucidation of
      the mechanism of action are recommended.

PMID- 21180472
TI  - Monitorization of drug content in furosemide and lorazepam tablets stored in
      multidose pill boxes.
AB  - BACKGROUND: Therapeutic nonadherence is a major health problem, particularly when
      therapeutic regimens are complex and long-lasting. Therefore, tools such as
      multidose pill boxes have been designed to provide the means for higher
      therapeutic compliance. However, no studies are available reporting on their
      capacity to keep the drug content of the stored tablets unaltered. OBJECTIVE:
      This work aimed at monitoring the drug content of tablets stored in multidose
      boxes for a period of two weeks. MATERIALS AND METHODS: Furosemide and lorazepam
      were selected as model drugs, given their frequent chronic use, which is coherent
      with the profile of medicines susceptible of storage in the referred boxes.
      Variations of the tablets drug content were assessed as a function of temperature
      (25 degrees C and 40 degrees C) and the presence of blister. RESULTS AND
      DISCUSSION: The obtained results allowed concluding that concerning temperature,
      only lorazepam tablets registered drug content alterations and only when stored
      at 40 degrees C. On the other side, it was concluded that the absence of blister
      does not compromise the drug content of the studied tablets. CONCLUSION: In the
      specific conditions of this study, the storage of these medicines in multidose
      boxes is considered reliable and adequate.

PMID- 21180471
TI  - Effect of Erythrina variegata seed extract on hyperlipidemia elicited by high-fat
      diet in wistar rats.
AB  - OBJECTIVE: To investigate the effect of the methanolic extract of Erythrina
      variegata (Linn.) var Orientalis (Fabaceae) seeds (MEEV) in reducing the
      cholesterol levels and as well as antioxidant in experimentally induced
      hyperlipidemic rats. MATERIALS AND METHODS: Doses of 200 and 400 mg/kg of the
      extract were evaluated for its effect on lipid profile, HMG-CoA reductase, and on
      antioxidant enzymes in high-fat diet (HFD) induced hyperlipidemia. RESULTS AND
      CONCLUSION: The elevated levels of total cholesterol, triglycerides, low-density
      lipoprotein, and very low density lipoprotein due to HFD was reduced by
      concurrent treatment with MEEV (200 and 400 mg/kg) significantly (P<0.001). A
      significant reduction (P<0.001) in high-density lipoprotein was noticed in HFD
      fed groups; however, a nonsignificant increment was produced by the
      administration of MEEV (200 and 400 mg/kg). The HMG-CoA reductase activity was
      increased in HFD fed animals significantly (P<0.001) and was reduced by MEEV 400
      mg/kg significantly (P<0.001). There was a noticed increase in the body weight
      and mesenteric fat pad weight in HFD fed group (P<0.001), which was reduced by
      the administration of MEEV (200 and 400 mg/kg). The antioxidant enzymes such as
      superoxide dismutase and catalase were reduced significantly in the HFD fed
      group, whose levels were increased significantly (P<0.001) by the administration
      of MEEV (200 and 400 mg/kg). Lipid peroxidation was increased in HFD fed animals,
      which was reduced significantly (P<0.001) by the treatment with MEEV (200 and 400
      mg/kg).

PMID- 21180473
TI  - Sensitive and selective method for the analysis of menthol from pharmaceutical
      products by RP-HPLC with refractive index detector.
AB  - OBJECTIVE: Liquid chromatography with refractive index (RI) detection has been
      found to be very useful for the determination of menthol from pharmaceutical
      products. A simple and rapid HPLC method has been developed for this purpose
      compared to conventional GC methods, requiring no special sample pretreatment for
      the determination of menthol from pharmaceutical products. MATERIALS AND METHODS:
      A chromatographic separation was achieved on a Inertsil ODS 3V (4.6mm*250mm,
      5MUm) column using water : methanol (30:70 v/v) as a mobile phase, at a flow rate
      of 1.0 ml/min. RESULTS: Method was validated as per ICH guidelines for various
      parameters such as precision, linearity, accuracy, solution stability,
      robustness, limit of detection and quantification. Results were found to be
      within acceptable limits. CONCLUSION: The method has been successfully applied
      for the quantification of menthol from syrup formulations. The developed method
      can be conveniently used by the quality control department to determine assay of
      menthol from pharmaceutical preparations.

PMID- 21180474
TI  - Spectrophotometric methods for determination of zolpidem tartrate in tablet
      formulation.
AB  - AIM: The study aims to develop simple, sensitive, rapid, accurate and precise
      spectrophotometric method for estimation of Zolpidem tartrate in tablet dosage
      forms. MATERIALS AND METHODS: For method I, II, III and IV in a series of 10 ml
      volumetric flask, aliquots of standard drug solution (100 ug/ml) in 0.1N HCl were
      transferred and diluted with same so as to give several dilutions in
      concentration range of 5-30 ug/ml, 5-30 ug/ml, 10-50 ug/ml and 5-40 ug/ml
      respectively of zolpidem tartrate. To 5 ml of each dilution taken in a separating
      funnel, (5 ml of bromo phenol red, bromo cresol purple, bromo cresol green and
      bromo phenol blue for method I, II, III and IV respectively) reagent and 5 ml of
      chloroform was added. Reaction mixture was shaken gently for 5 min and allowed to
      stand so as to separate aqueous and chloroform layer. Absorbance maxima measured
      at 407 nm, 417 nm, 412 nm and 415 nm for method I, II, III and IV respectively.
      RESULTS: The recovery studies were found close to 100 % that indicates accuracy
      and precision of the proposed methods. The statistical analysis was carried out
      and results of which were found satisfactory. Standard deviation values were
      found low that indicated reproducibility of the proposed methods. CONCLUSION:
      Based on results the developed methods could be used for routine estimation of
      zolpidem tartrate from tablet formulations.

PMID- 21180475
TI  - Fluorescent labeling of human albumin using the new aromatic dialdehyde labels
      and the study of innerfilter effect.
AB  - The labels naphthalene-2,3-dicarboxaldehyde (NDA), 1-phenylnaphthalene-2,3
      dialdehyde (PhiNDA), and anthracene-2,3-dialdehyde (ADA) have been used as
      fluorigenic reagents. They formed fluorescent derivatives with proteins. The
      derivatives formed are in fact isoindoles. The fluorescence decay of the labels
      antibody was found to extend over a period of 4, 8, and 10 h for PhiNDA, ADA, and
      NDA-derivative, respectively. Protein formed is comparatively less stable as
      compared to simple amino acids. In relation to innerfilter effect, the addition
      of cytochrome C, myoglobin, and ATP as absorbers to label-human albumin
      fluorophores appeared to have quenched the fluorescence. In the case of using NDA
      as label, the fluorescence was quenched roughly 70%, 24%, and 58% for addition of
      cytochrome C, myoglobin, and ATP, respectively. The labels used were found to
      give rapid, reproducible, and reliable results.

PMID- 21180476
TI  - Spectrophotometric method for simultaneous estimation of atenolol in combination
      with losartan potassium and hydrochlorothiazide in bulk and tablet formulation.
AB  - AIM: To develop a simple, accurate, rapid and precise UV spectrophotometric
      method for the estimation of atenolol in combination with losartan potassium and
      hydrochlorothiazide. MATERIALS AND METHODS: The method employs formation and
      solving simultaneous equation using 251.60 nm and 224.20 nm for losartan
      potassium and atenolol, 224.20 and 271.60 for atenolol and hydrochlorothiazide as
      two analytical wavelengths, using methanol water as a solvent. RESULTS AND
      CONCLUSION: The linearity was observed in the concentration range of 5-30 ug/ml
      (r=0.9991) for losratan pottassium, 2 - 12 ug/ml (r = 0.9995) for atenolol and 2 
      14 ug/ml (r = 0.9993) for hydrochlorothiazide. The results of the method were
      validated statistically and by recovery studies.

PMID- 21180477
TI  - Bacterial virulence traits: A potential area of study for drug development.

PMID- 21180478
TI  - Periodontitis leads to VAP in ICU patients: A dental note.

PMID- 21180479
TI  - Urbanization and mental health.

PMID- 21180480
TI  - Prevalence of obsessive compulsive symptoms among patients with schizophrenia.
AB  - BACKGROUND: Obsessive compulsive symptoms in schizophrenia are well recognized
      but are a less-researched entity. These symptoms have important implications for
      management and prognosis. AIM: To find out the prevalence of obsessive compulsive
      symptoms among patients with schizophrenia. MATERIALS AND METHODS: A total of 90
      hospitalized patients with schizophrenia diagnosed according to DCR of ICD-10
      criteria were selected for the study. Padua inventory and Yale-Brown Obsessive
      Compulsive Scale were applied to find out the prevalence and nature of obsessive
      compulsive symptoms. RESULTS: It was found that 10% of schizophrenic patients had
      obsessive compulsive symptoms. CONCLUSION: Obsessive compulsive symptoms are
      prevalent in patients with schizophrenia. The presence of comorbidity should be
      explored for adequate management.

PMID- 21180481
TI  - Impact of age and level of experience on occupational stress experienced by non
      gazetted officers of the central reserve police force.
AB  - BACKGROUND: The study explores the effect of demographic variables such as age
      and level of experience on the level of stress experienced by non-gazette
      officers of the Central Reserve Police Force (CRPF). MATERIALS AND METHODS: A
      purposive sample of 163 CRPF personnel was chosen. The Police Stress Inventory
      developed for use among CRPF personnel was administered. Various statistical
      parameters such as mean, standard deviation, standard error, mean difference and
      single-factor ANOVA were used to analyze the data. CONCLUSION: The study strongly
      indicates the relationship between stress and demographic variables such as age
      and level of experience.

PMID- 21180482
TI  - Comorbid psychiatric disorders in substance dependence patients: A control study.
AB  - BACKGROUND: The purpose of this study was to investigate the comorbidity of
      mental disorders among a random sample of substance dependence patients from a
      psychiatric inpatients department and the general population. MATERIALS AND
      METHODS: Comprehensive data was collected from inpatients with substance
      abuse/dependence and comorbidity of mental disorders at the Ranchi Institute of
      Neuropsychiatry and Allied Sciences (RINPAS) and from normal controls from the
      general population during the period January 2007 to May 2007. RESULTS: The
      results show that the most prevalent comorbid disorders in substance dependence
      patients and substance abusers were depressive disorders. CONCLUSIONS: The
      majority of substance dependence patients suffered from comorbid mental
      disorders. Comorbidity needs to be taken into account when analyzing the
      relationship between substance dependence and depression and in planning
      treatment strategies for comorbid conditions.

PMID- 21180483
TI  - Intracranial (structural) changes in obsessive- compulsive disorder: A
      computerized tomography scan study.
AB  - OBJECTIVE: To assess intracranial structural changes in obsessive-compulsive
      disorder (OCD) with CT scan. MATERIALS AND METHODS: Thirty patients of OCD
      between 21 and 40 years of age and fulfilling various inclusion and exclusion
      criteria were compared with control group. CT scans of all the patients and
      controls were taken and compared with regard to ventricular size, Evan's ratio
      and ventricular brain ratio (VBR). RESULTS: Patients of OCD were found to have
      greater cortical atrophy and scored significantly higher in frontal and parietal
      area. Only 4 patients had enlarged ventricles, and there were none with a smaller
      ventricle. Mean Evan's ratio of patients was lower than that of the control group
      but the difference was statistically nonsignificant. The mean VBR of patients was
      lower than that of the control group and the difference was highly significant.
      CONCLUSIONS: The evidence of neuro-radiological abnormalities in patients with
      OCD suggests that these disorders should not be considered merely functional in
      the traditional sense.

PMID- 21180484
TI  - Students' perception about mental illness.
AB  - BACKGROUND: In developing countries like India, there are evidences that stigma
      associated with mental illness is increasing. As in parts of the developing
      world, with advancement of urbanization and rapid industrialization, people tend
      to react in a very peculiar and biased way when they confront a mentally ill
      person. MATERIALS AND METHODS: The present study aimed to find out students'
      opinion about mental illness. A total of 100 students (50 male and 50 female)
      from Ranchi University were purposively recruited for the study, and the 51-item
      Opinion about Mental Illness (OMI) Scale was administered. RESULTS: Majority of
      the students were from Hindu families, of whom 42 (84%) were males and 38 (68%)
      were females. With regard to OMI scale, the item, viz., 'The law should allow a
      woman to divorce her husband as soon as he has been confined in mental hospital
      with a severe mental illness', both male (46%) and female (56%) students were
      neutral (significant at 0.014, P < 0.05). CONCLUSION: Overall no significant
      level of difference emerged between male and female students with regard to
      opinion about mental illness.

PMID- 21180485
TI  - Subjective burden on spouses of schizophrenia patients.
AB  - BACKGROUND: There is limited information from India on subjective burden on
      spouses of schizophrenia patients. The aim of the present study was to assess and
      compare patterns of subjective burden on spouses of schizophrenia patients.
      MATERIALS AND METHODS: The present study was conducted at the OPD level, and
      follow-up was done at the Ranchi Institute of Neuropsychiatry and Sciences
      (RINPAS) during the period May 2008 to November 2008. Tools utilized were
      sociodemographic data sheet, Family Burden Interview Schedule developed by Pai
      and R. L. Kapur (1981). The sample comprised of 50 samples of spouses (25 male
      and 25 female spouses of schizophrenia patients). METHODS: The present study was
      conducted at the OPD level, and follow-up was done at the Ranchi Institute of
      Neuropsychiatry and Sciences (RINPAS) during the period May 2008 to November
      2008. Tools utilized were sociodemographic data sheet, Family Burden Interview
      Schedule developed by Pai and R. L. Kapur (1981). The sample comprised of 50
      samples of spouses (25 male and 25 female spouses of schizophrenia patients).
      RESULTS: The findings suggest that both the groups, viz., male and female spouses
      of schizophrenia patients, showed moderate level of subjective burden, i.e., 13
      (52%) and 15 (60%) male and female spouses, respectively, which was statistically
      found to be insignificant. CONCLUSION: No significant difference was found
      between male and female spouses of schizophrenia patients with regard to the
      level of subjective burden.

PMID- 21180486
TI  - Innovative work behavior of managers: Implications regarding stressful challenges
      of modernized public- and private-sector organizations.
AB  - BACKGROUND: The present study was firstly aimed to find out the nature of
      stressful life events arising out of the innovative challenges in modernized
      organizations; and secondly, it tried to identify the relationship between
      innovative work behavior of managers and the levels of stress arising out of
      stressful events in modernized organizations (public and private) in West Bengal.
      MATERIALS AND METHODS: Data was collected from a sample of 200 managers, by using
      3 tools (General Information Schedule, Life Event Inventory and Innovative Work
      Behavior Scale) through a face-to-face interview. Responses were subjected to
      both quantitative and qualitative analyses. The data was statistically treated
      for 't' and ANOVA. RESULTS: Data highlighted the fact that the qualitative
      profile of stressful events in the lives of managers expressed specificity in
      terms of their organizational type (public- and private-sector modernized
      organizations), and levels of stress from stressful life events were
      significantly higher among the modernized private-sector managers than those
      among public-sector managers. The prevalence of innovative work behavior was
      moderately higher among managers of private-sector modernized organizations than
      their counterparts in public-sector organizations. The trends of innovative work
      behavior of the managers indicated much variability due to interaction of their
      level of perceived stressful challenges for innovation and the global forces of
      change that have unleashed dynamic, systematic and higher expectation level from
      them.

PMID- 21180487
TI  - Occupational stress and mental health of cardiac and noncardiac patients.
AB  - BACKGROUND: Much of the research studies have shown that occupational stress is
      one of the strong determinant factors of coronary heart diseases among people in
      general. However, exploring the extent to which the type or nature of ailments
      and its subsequent risk factors have an effect on the onset of mental health will
      help evolve suitable preventive measures. The present study attempts to explore
      the status of mental health and occupational stress with respect to 2 categories
      of patients: Those who are suffering from cardiac problems and those suffering
      from noncardiac health problems. MATERIALS AND METHODS: Occupational Stress
      Questionnaire and Mental Health Questionnaire were administered to both cardiac
      and noncardiac patients. The cardiac group consisted of 40 patients who were
      being treated at the cardiology department of a reputed hospital, and noncardiac
      group (40 patients) consisted of outpatients of the same hospital being treated
      for noncardiac problems like knee pain, headache, etc. Responses to these self
      reported questionnaires were subjected to statistical analysis to find out the
      difference between cardiac and noncardiac groups. RESULTS: The results revealed
      that cardiac patients tend to have lower levels of mental health than noncardiac
      patients. Similarly, cardiac patients were reported to have higher levels of
      stress due to role ambiguity, powerlessness, intrinsic impoverishment and
      unprofitability. CONCLUSIONS: The implications of the study were implementation
      of interventions to improve the internal strength of cardiac patients to overcome
      various aspects of occupational stress.

PMID- 21180488
TI  - Neurocognitive psychotherapy for adult attention deficit hyperactive disorder.
AB  - Previously thought as a childhood disorder, attention-deficit hyperactivity
      disorder (ADHD) is reported to be spreading at an increasing rate and affecting
      4% to 5% of the adult population. It is characterized by persistent problems of
      inattention, hyperactivity and impulsivity. We present the case of an adult ADHD
      patient intervened with neurocognitive psychotherapy.

PMID- 21180489
TI  - Partial Kluver-Bucy syndrome as a delayed manifestation of head injury.
AB  - After traumatic brain injury (TBI), the most disabling problems are generally
      related to neuropsychiatric sequelae, including personality change and cognitive
      impairment, rather than neurophysical sequelae. Kluver-Bucy syndrome (KBS) is a
      rare neurobehavioral condition, first described in 1937 as an experimental
      neurobehavioral syndrome in monkeys with bitemporal brain lesions. The syndrome
      in man was subsequently observed to be transient or permanent in a variety of
      neurodegenerative disorders and after traumatic, nontraumatic and infectious
      brain injury. However, partial KBS may occur in the absence of the classic
      bilateral temporal lesion, though rare. Pharmacological treatment of post-TBI
      neuropsychiatric sequelae consists of symptomatic, functional and hypothetical
      approaches. Specific pharmacological treatment consists of antipsychotics, anti
      kindling anticonvulsants or a combination thereof. A case of partial KBS
      presenting as delayed manifestation of traumatic brain injury that improved with
      carbamazapine and antipsychotics is presented.

PMID- 21180490
TI  - Hallucinations: Etiology and clinical implications.
AB  - The literature on hallucinations is reviewed, including history; theoretical
      background from physiological, biochemical and psychological points of view;
      classification; causation; presentation in different psychiatric and neurological
      disorders and in normal persons. The available evidence suggests that
      hallucinations result from a failure of the metacognitive skills involved in
      discriminating between self-generated and external sources of information.
      Management of hallucinations is briefly discussed.

PMID- 21180491
TI  - Hypothesis testing, type I and type II errors.
AB  - Hypothesis testing is an important activity of empirical research and evidence
      based medicine. A well worked up hypothesis is half the answer to the research
      question. For this, both knowledge of the subject derived from extensive review
      of the literature and working knowledge of basic statistical concepts are
      desirable. The present paper discusses the methods of working up a good
      hypothesis and statistical concepts of hypothesis testing.

PMID- 21180492
TI  - Possible psychosocial strategies for controlling violence against women.
AB  - Women, the fair sex, are considered to be the weaker sex and one of the most
      powerless and marginalized sections of our society. Violence against women and
      girls continues to be a global epidemic. It is present in every country, cutting
      across boundaries of culture, class, education, income, ethnicity and age. A
      growing body of research studies indicates that 20% to 50% (varying from country
      to country) of women have experienced domestic violence. A multilayered strategy
      that addresses the structural causes of violence against women is needed.
      Strategies and interventions attempting to address violence against women should
      be guided by 5 underlying principles: Prevention, protection, early intervention,
      rebuilding the lives of victims/survivors and accountability. When planning
      interventions, there are a variety of stakeholders who should be borne in mind.
      Key areas for intervention include encouraging women empowerment; advocacy and
      awareness raising; education for building a culture of nonviolence; encouraging
      active participation of women in political system; resource development; direct
      service provision to victims, survivors and perpetrators; networking and
      community mobilization; direct intervention to help victims/survivors rebuild
      their lives; legal reform; monitoring interventions and measures; early
      identification of 'at risk' families, communities, groups and individuals; and
      data collection and analysis.

PMID- 21180493
TI  - Model of organizational stress for use within an occupational health
      education/promotion or well-being of members of the organization.
AB  - This paper introduces a simple model of organizational stress which can be used
      to educate or inform employees, personnel and health professionals about the
      relationship between potential work-related stress hazards, individual and
      organizational symptoms of stress, negative outcomes and financial costs. The
      components of the model relate directly to a recent Health and Safety Executive
      publication (Cox, 1993) which focuses on improving and maintaining employee
      health and well-being.

PMID- 21180494
TI  - Hyponatremia-induced psychosis in an industrial setting.

PMID- 21180495
TI  - Portal hypertensive biliopathy: Can we prevent it?

PMID- 21180496
TI  - Minimally invasive surgery in neonates and infants.
AB  - Minimally invasive surgery (MIS) has significantly improved the field of surgery,
      with benefits including shorter operating time, improved recovery time,
      minimizing stress and pain due to smaller incisions, and even improving
      mortality. MIS procedures, including their indications, impact, limitations, and
      possible future evolution in neonates and infants, are discussed in this article.

PMID- 21180497
TI  - Surgical management and outcome analysis of stage III pediatric empyema thoracis.
AB  - AIM: Report of 125 pediatric patients of empyema thoracis treated by open
      decortication, highlighting the presentation, delay in referral, operative
      findings, the response to surgical intervention and follow-up. MATERIALS AND
      METHODS: All the children who underwent open decortication for stage III empyema
      thoracis during the study period were included. Preoperative workup included
      hemogram, serum protein, chest radiographs and contrast-enhanced computed
      tomographic (CECT) scan of the chest. RESULTS: One hundred and twenty-five
      patients (81 males, 44 females) (age 3 months-12 years, mean 4.9 years) were
      operated during a 4.5-year period. Among them, two children underwent bilateral
      thoracotomies. Also, 81.6% patients were referred 3 weeks after the onset of
      disease (mean duration 9 weeks). Intercostal chest drainage (ICD) had been
      inserted in (119) 95% cases. Thickened pleura, multiloculated pus and lung
      involvement were invariably seen on CECT scan. Bronchopleural fistula was present
      in 10 patients and empyema necessitatis in 2. Decortication, removal of necrotic
      tissue and closure of air leaks was performed in all the patients. Necrotizing
      pneumonia was seen in (35) 27.5% cases. Mean duration of postoperative ICD was 7
      days. Follow-up ranged from 3 months to 4 years (mean 12 months). There was no
      mortality. Six patients had proven tuberculosis. CONCLUSIONS: The duration of the
      disease had a direct relationship with the thickness of the pleura and injury to
      the underlying lung. Delayed referral causes irreversible changes in the lung
      prolonging recovery. Only 18% presented within the early period of the disease.
      Meticulous open surgical debridement gives gratifying results. The status of the
      lung at the end of surgery is a major prognostic factor.

PMID- 21180498
TI  - Psychosocial burden and quality of life in parents of children with anorectal
      malformation.
AB  - AIM: To assess the psychosocial burden and quality of life in parents of children
      with anorectal malformation. SUBJECTS AND METHODS: This is a prospective study
      conducted in a tertiary care specialty hospital. Sample consisted of 50 parents
      (care givers), having children with anorectal malformation in the age group of 0
      14 years. Data were collected through a semi structured interview with the care
      givers, using Zarit Burden Interview for assessing extent of burden and WHOQOL
      BREF for assessing different aspects of quality of life. STATISTICAL ANALYSIS
      USED: frequencies, percentages, mean and standard deviations were calculated for
      analyzing the data. RESULTS: The study reveals greater psychosocial burden and
      poor quality of life, in terms of the psychological and environmental aspects as
      compared to the physical and social aspects, among the care givers. CONCLUSIONS:
      The study found increased psychosocial burden and negative impact on the quality
      of life of parents, which varies with the stages of management and proper
      continuous counseling is recommended.

PMID- 21180499
TI  - Vaginal agenesis: Experience with sigmoid colon neovaginoplasty.
AB  - AIM: Objective of this study is to report our experience with sigmoid
      vaginoplasty in adolescents. MATERIALS AND METHODS: A retrospective study of
      children with vaginal atresia and Mayer-Rokitansky-Kuster-Hauser syndrome. The
      sigmoid segment was used for vaginoplasty in all the cases. RESULTS: Eight
      children were studied over a period of 7 years. The postoperative complications
      were ileus in 2, mucosal prolapse of the neovagina in 1, and minor wound
      infection in 1 patient. Seven patients are on regular follow-up. All the
      neovaginas were patent and functional. One patient had unacceptable perineal
      appearance, that is, badly scarred perineum as a late complication. None of the
      patients had vaginal stenosis or excessive mucus discharge, during follow-up
      visits. Out of the 7 patients, 2 patients are sexually active and satisfied.
      CONCLUSIONS: Sigmoid vaginoplasty is a safe and acceptable procedure for vaginal
      agenesis with good cosmetic results and acceptable complications rate. Sigmoid
      colon vaginoplasty is the treatment of choice because of its large lumen, thick
      walls resistant to trauma, adequate secretion allowing lubrication, not
      necessitating prolonged dilatation, and short recovery time.

PMID- 21180500
TI  - Epidermoid cyst of clitoris mimicking clitoromegaly.
AB  - Clitoromegaly in pediatric and adolescent age group is usually indicative of a
      disorder of sexual differentiation. We report a girl child presenting with
      clitoral enlargement due to an epidermoid cyst. The cyst was excised with
      complete cosmetic recovery.

PMID- 21180501
TI  - Gastric, pancreatic, and ureteric duplication.
AB  - We report a case of an 8-month-old, asymptomatic child who was incidentally
      detected to have two cystic structures in the abdomen. Surgical exploration
      revealed a gastric and pancreatic duplication cyst along with a blind-ending
      duplication of the right ureter. Excision of the duplications was relatively
      straightforward, and the child made an uneventful recovery. This constellation of
      duplications has not been reported before.

PMID- 21180502
TI  - Acute gastric volvulus in operated cases of tracheoesophageal fistula.
AB  - A report of two neonates of esophageal atresia with tracheoesophageal fistula who
      had acute gastric volvulus in the postoperative period and required gastropexy
      after correction of the volvulus. Such postoperative complication has not been
      reported in the literature so far.

PMID- 21180503
TI  - Coeliac disease in a child with anorectal malformation: The importance of
      considering other causes of diarrhea.
AB  - We present the case of an Indian child with a high anorectal malformation (ARM)
      who postoperatively had troublesome fecal incontinence. Based on a dietary
      history, weight loss, and diarrhea, a duodenal biopsy was performed that revealed
      coeliac disease. Since being on a gluten-free diet, her symptoms have improved
      dramatically. To the best of our knowledge this is the first report in the
      English literature of such an association between ARMs and coeliac disease.
      Dietary modification alone can dramatically improve symptoms in these children.

PMID- 21180504
TI  - Spontaneous duodenal fistulization of pseudocyst of pancreas: A rare entity in
      children.
AB  - The spontaneous resolution of pseudopancreatic cyst due to internal fistulization
      into the duodenum in a 4-year-old male child is described here. This is rare and
      the child presented initially with features of duodenal obstruction. Upper
      gastrointestinal endoscopy and computed tomography scan confirmed the diagnosis
      and the unusual mode of resolution of this entity.

PMID- 21180505
TI  - Esophageal perforation following bite of inner tube of automobile tyre: An
      unusual cause of barotrauma.
AB  - An 8-year-old child presented with severe chest pain and respiratory distress
      after he accidentally bit an automobile tyre tube which burst into his mouth. The
      chest radiograph revealed left-sided pneumothorax. Both esophagogram and computed
      tomogram (CT) scan revealed a perforation of the distal third of esophagus with
      extravasation of contrast on left side. The patient was treated conservatively
      with gastrostomy feeds and antibiotics for 5 weeks with a good response.

PMID- 21180506
TI  - Recurrent plunging ranula.
AB  - We report two cases of plunging ranula, which had recurred after
      marsupialization. Both were successfully treated by removal of the ipsilateral
      sublingual gland. A brief review of the literature regarding the treatment
      options is presented.

PMID- 21180507
TI  - 3D multidetector CT angiographic evaluation of intralobular bronchopulmonary
      sequestration.
AB  - We report a case of intralobar pulmonary sequestration with special emphasis on
      computed tomography (CT) angiography in determining the arterial supply and
      venous drainage, thus providing a detailed knowledge of the vasculature, which is
      of vital importance in surgery. The 3D volume rendering technique and maximum
      intensity projection images provide the vascular road map for the surgeon.

PMID- 21180508
TI  - Esophageal atresia with tracheo-esophageal fistula.

PMID- 21180509
TI  - Undergraduate medical education and pediatric surgery.

PMID- 21180510
TI  - Editorial.

PMID- 21180511
TI  - Chemoprevention of esophageal adenocarcinoma.
AB  - The incidence of esophageal adenocarcinoma (EAC) is rising rapidly in Western
      countries, and effective chemoprevention for this malignancy is lacking.
      Endoscopic surveillance of patients with Barrett's esophagus is currently
      employed to diagnose EAC at earlier stages, but this strategy has several
      limitations. Non-steroidal anti-inflammatory drugs and proton pump inhibitors are
      the most promising agents for prevention of EAC, and a randomized controlled
      trial of aspirin and esomeprazole is ongoing. Other agents under investigation
      include green tea, berries, and antioxidants. Cost-effectiveness analyses have
      shown that chemopreventive agents need to be highly effective at preventing EAC
      in order to have benefit beyond endoscopic surveillance.

PMID- 21180512
TI  - Systemic treatment of advanced colorectal cancer: tailoring therapy to the tumor.
AB  - Colorectal cancer is a prevalent disease in Western countries. While prevention
      through screening is the best approach to combat the development of colorectal
      cancer through the removal of precursor adenomas, many patients present with
      advanced disease that will require surgery and systemic therapy to improve
      survival. With reference to systemic therapy, the median survival of patients
      with metastatic colorectal cancer (those with tumor spread to lymph nodes or
      distant sites) has improved over the past three decades due to the introduction
      of 5-fluorouracil (5-FU), its subsequent biomodulation, and the addition other
      chemotherapeutic agents. There is now evidence that the biology of the colorectal
      tumor, in addition to the stage of colorectal cancer, may predict response to 5
      FU-based therapy. More recently, systemic biological therapies that target
      signaling processes for tumor growth, such as epidermal growth factor receptor,
      and vascular endothelial growth factor, are also effective in improving patient
      survival with metastatic colorectal cancer. The use of a combination of systemic
      therapies that include chemotherapy and biologic therapy should continue to
      increase patient survival with metastatic colorectal cancer through appropriately
      designed clinical trials. Treatments based on the biology of the colorectal tumor
      also need to be examined through clinical trials.

PMID- 21180513
TI  - Efficacy and safety of adalimumab in Crohn's disease.
AB  - Adalimumab (ADA) is a subcutaneously (SC) self-administered fully human Ig G1
      monoclonal antibody directed against tumor necrosis factor alpha (TNFce). In the
      CLASSIC dose-ranging trial, ADA was superior to placebo for inducing remission in
      patients with moderate-to-severe Crohn's disease (CD) naive to TNFa inhibitor
      therapy. In CLASSIC II, patients in remission following CLASSIC I maintained
      remission for up to 56 weeks while on ADA. In CHARM, approximately 40% of the 499
      patients with moderate-to-severe CD who responded to ADA, maintained remission at
      26 and 52 weeks, thus confirming long-term efficacy. ADA demonstrated steroid
      sparing properties, beneficial effects in patients with perianal fistulas, and
      decreases in rates of hospitalization and surgery. Sub-group analyses
      demonstrated similar remission rates irrespective of concomitant
      immunosuppressive use or previous exposure to other TNFa inhibitor therapy. In
      the GAIN trial, 325 patients who had either lost response or become intolerant to
      infliximab (IFX) were randomized to recieve ADA induction therapy or placebo. In
      this difficult-to-treat patient population, 21% achieved remission and half
      demonstrated clinical benefit from ADA induction therapy. Injection site
      reactions may occur with SC ADA (2-5% of patients), which are generally less
      dramatic in nature than infusion reactions experienced with intravenous IFX.
      Immunogenicity occurs with all monoclonal antibodies; however, in the CD
      development program anti-ADA antibodies were detected at low rates (0.7 and 2.6%
      of patients in the CLASSIC I and CLASSIC II studies, respectively). Based on
      robust short- and long-term efficacy data from large randomized controlled trials
      and a favorable safety signal, ADA has become a key addition to the therapeutic
      armamentarium in the treatment of moderate-to-severe CD.

PMID- 21180514
TI  - Enteroendocrine cells: neglected players in gastrointestinal disorders?
AB  - Enteroendocrine cells (EEC) form the basis of the largest endocrine system in the
      body. They secrete multiple regulatory molecules which control physiological and
      homeostatic functions, particularly postprandial secretion and motility. Their
      key purpose is to act as sensors of luminal contents, either in a classical
      endocrine fashion, or by a paracrine effect on proximate cells, notably vagal
      afferent fibres. They also play a pivotal role in the control of food intake, and
      emerging data add roles in mucosal immunity and repair. We propose that EEC are
      fundamental in several gastrointestinal pathologies, notably Post-infectious
      Irritable Bowel Syndrome, infectious enteritis, and possibly inflammatory bowel
      disease. Further work is needed to fully illustrate the importance, detailed
      biology and therapeutic potential of these frequently overlooked cells.

PMID- 21180515
TI  - Current status of antiviral therapy for hepatitis B.
AB  - Chronic hepatitis B (CHB) is a major public health problem affecting up to 400
      million people globally. Complications of CHB including liver failure and
      hepatocellular carcinoma result in 1.2 million deaths per year, making CHB the
      10th leading cause of mortality worldwide. The natural history of CHB is variable
      and complex. The past decade witnessed important developments for the therapy of
      hepatitis B and marked the new era of oral therapy. The ultimate goal of CHB
      therapy is to arrest the progression of liver injury and to prevent the
      development of liver failure and hepatocellular carcinoma. Currently, six agents
      are approved for the treatment of CHB. Each of these agents, given as
      monotherapy, has been shown to produce virological, biochemical, and histological
      benefits for both HBeAg positive and negative CHB. There are, however,
      limitations in spite of their efficacy. The significant side-effect profile of
      interferon, for example, limits its long-term use. The approved oral agents are
      tolerable with prolonged use but drug resistance could limit long-term
      monotherapy. To date, combination therapy with nucleoside analogue and pegylated
      interferon or two nucleos(t)ide analogues given for one year does not show
      superiority in durability of response compared to monotherapy. Ongoing research
      effort is critical to identify the ideal hepatitis B therapy that is safe,
      effective, and produces durable response with a finite course of therapy. It is
      equally important to conduct a well designed, prospective natural history study
      to identify predictors of disease progression. This will accurately guide
      treatment strategy for this important disease.

PMID- 21180516
TI  - What are the therapeutic advances in gastroenterology? opinions from world
      experts.

PMID- 21180517
TI  - Phlegmonous gastritis after endoscopic submucosal dissection for early gastric
      cancer.
AB  - A 74-year-old man with diabetic nephropathy developed epigastric pain and high
      fever after endoscopic submucosal dissection (ESD) for early gastric cancer.
      Gastroscopy, endoscopic ultrasonography and computed tomography showed ulceration
      with a purulent lake, thickened entire gastric mucosal layers suggesting focal
      abscess formation, leading to the diagnosis of phlegmonous gastritis. He
      underwent total gastrectomy as an emergency. Histological findings of the
      resected specimen showed severe inflammatory cell infiltration and multiple focal
      abscess formation spreading to the entire gastric wall. In patients with poorer
      general conditions, phlegmonous gastritis should be considered as a serious
      complication after ESD, indicating a requirement of antibiotic prophylaxis.

PMID- 21180518
TI  - Upper gastrointestinal dieulafoy's lesions and endoscopie treatment: first report
      from a mexican centre.
AB  - The aim was to evaluate the initial success, rebleeding rate, need for emergent
      surgery, and mortality rates of patients with Dieulafoy's lesion (DL) and
      endoscopic treatment (ET). Patients with DL from a tertiary center were included.
      We included 20 patients with follow-up of 90 (60-550) days. The lesser curvature
      was the most common localization. Initial success, rebleeding, and emergent
      surgery requirement were observed in 90%, 10%, and 15%, respectively. No
      objective variables were related with response to ET. In conclusion, ET is secure
      and useful in patients with DL and it must be considered as the first-line
      treatment modality.

PMID- 21180519
TI  - Endoscopic ultrasound-guided fine needle injection for cancer therapy: the
      evolving role of therapeutic endoscopic ultrasound.
AB  - Endoscopic ultrasound (EUS) is central to the diagnosis and staging of many
      malignancies, but now has an evolving role in cancer therapy. EUS-guided fine
      needle injection (FNI) is already used for palliative interventions such as
      treatment of pain through nerve blockade and to guide biliary decompression when
      conventional ERCP is not possible. More recently, EUS-FNI has been used to
      deliver specific anti-tumor agents for pancreatic cyst ablation and local control
      of tumor growth in patients with unresectable solid malignancies. The agents used
      to date include ethanol, brachytherapy seeds, and chemotherapeutic agents such as
      paclitaxel. In addition, FNI of new immunomodulating cell cultures such as mixed
      lymphocyte and dendritic cell cultures has also been reported, as has FNI of
      several different viral vectors for antitumor therapy. Although experience with
      these agents remains preliminary, EUS-FNI is a minimally invasive approach to
      deliver local antitumor agents, and is likely to have an expanding role in cancer
      therapy.

PMID- 21180520
TI  - Eradication of helicobacter pylori to prevent gastroduodenal diseases: hitting
      more than one bird with the same stone.
AB  - Helicobacter pylori (H. pylori) are gram-negative bacteria that selectively
      colonizes the gastric mucosa. The prevalence of H. pylori infection varies from
      20 to 50% in industrialized countries to over 80% in developing countries. The
      infection may persist lifelong without specific treatment. Prolonged infection
      and inflammation due to bacterial virulence and host genetic factors will lead to
      chronic gastritis. A certain portion of infected patients then develop more
      severe pathologies such as peptic ulcer (10-15%), gastric cancer (1%), and mucosa
      associated lymphoid tissue lymphoma (50.01%). Although the majority of infected
      patients remain asymptomatic, much of the evidence has shown that eradication of
      H. pylori infection can reduce the recurrence of peptic ulcer and benefit a
      substantial portion of patients with nonulcer dyspepsia. Though controversial in
      population-based clinical trials, several cost-effectiveness analyses also reveal
      that H. pylori eradication is cost effective in the primary prevention of gastric
      cancer. Therefore, the discovery of H. pylori offers the chance to prevent
      several gastroduodenal diseases by means of their eradication. In other words,
      gastroenterologists could hit more than one bird with one stone. However, there
      are concerns regarding application of a 'test and treat' strategy in the general
      population. In this review, we will focus on current evidence of H. pylori
      eradication in the primary and secondary prophylaxis of gastric cancer and peptic
      ulcer disease.

PMID- 21180524
TI  - How should We Classify and Treat Patients with Functional Gastrointestinal
      Disorders?

PMID- 21180521
TI  - Barrett's esophagus and the increasing role of endoluminal therapy.
AB  - Barrett's esophagus, or the presence of specialized intestinal mucosa in the
      esophagus that has a malignant potential, has experienced a rapid increase in
      diagnosis and prevalence over the past few decades. Once thought to progress to
      adenocarcinoma in an orderly sequence of increasing dysplasia, recent data
      suggest the process can be more random. In combination with targeted surveillance
      endoscopy, recent improvements in technology have aided endoluminal therapy in
      becoming a cost-effective adjunct to medication. When used in combination, in
      particular, these ablative therapies have become suitable, if not preferable,
      alternatives to surgery in many patients.

PMID- 21180525
TI  - Perception of Colorectal Cancer Risk does not Enhance Participation in Screening.
AB  - High participation is a key requirement for effective cancer screening. Many
      strategies to improve participation hold that a person's knowledge and beliefs
      dictate screening behavior. We compared perception of colon cancer risk in
      participants and nonparticipants in a population-based study of screening
      colonoscopy, and also assessed past screening behavior. Surprisingly, while past
      screening behavior was a predictor of participation, we found that participants
      perceived their risk of colorectal cancer to be significantly and substantially
      lower than the real figure and that of nonparticipants. Our data suggest that
      health promotion strategies aimed at improving health knowledge may not be
      effective in improving population screening rates.

PMID- 21180526
TI  - Autoimmune diseases in coeliac disease: effect of gluten exposure.
AB  - INTRODUCTION: the prevalence of autoimmune diseases is increased in patients with
      coeliac disease. Duration of gluten exposure seems to predispose adolescents with
      coeliac disease to autoimmune diseases. AIM: In a retrospective cohort study, we
      assessed the relationship between autoimmune disorders and actual gluten exposure
      in patients with coeliac disease. PATIENTS AND METHODS: the frequency of
      autoimmune disorders was evaluated in 64 patients (53 females, 11 males, mean age
      29 years, range 16-63) with coeliac disease. The effect of age at the end of
      follow up, age at diagnosis of coeliac disease, actual gluten-exposure time,
      gender and diagnostic delay was assessed. RESULTS: the prevalence of autoimmune
      diseases was 17%. Mean duration of gluten exposure was 26 and 25 years for
      patients with and without autoimmunity, respectively. Logistic regression showed
      that a longer mean follow up (P1/40.044) was related to the prevalence of
      autoimmune disorders while actual gluten exposure was not predictive. CONCLUSION:
      in this study, the prevalence of autoimmune diseases in patients with late
      coeliac disease diagnosis does not correlate with duration of gluten intake.
      Confirmatory prospective, multicentre studies of the effect of gluten-free diet
      are needed in adults.

PMID- 21180528
TI  - Causes of, and therapeutic approaches for, proton pump inhibitor-resistant
      gastroesophageal reflux disease in Asia.
AB  - Proton pump inhibitors (PPIs) are the most widely used drugs for treatment of
      gastroesophageal reflux disease. However, approximately 20% of patients with
      reflux esophagitis and 40% of those with nonerosive reflux diseases complain of
      troublesome symptoms, even during treatment with PPIs. In patients with reflux
      esophagitis, dose escalation and co-administration with a histamine H(2)-receptor
      antagonist are potential approaches, since the major cause of PPI resistance is
      incomplete suppression of gastric acid secretion. On the other hand, for patients
      with nonerosive reflux disease, switching from PPIs to pain modulators is often
      necessary for improvement of symptoms, since 25% of patients with nonerosive
      reflux disease have symptoms not caused by gastroesophageal acid reflux.
      Therapeutic approaches for PPI-resistant patients with reflux esophagitis and
      nonerosive reflux diseases are considered according to pathogenesis.

PMID- 21180527
TI  - Treatment options for nonalcoholic Fatty liver disease.
AB  - Nonalcoholic fatty liver disease comprises a range of disorders from steatosis
      and steatohepatitis through to cirrhosis. Nonalcoholic steatohepatitis can
      progress to cirrhosis and liver-related death. Therefore, managing this common
      disorder is becoming an important public health issue. Lifestyle measures are
      commonly suggested but robust data are lacking. Trials with antioxidants (vitamin
      E, betaine) as well as cytoprotectants (ursodeoxycholic acid) have been
      disappointing. While data for insulin sensitizers such as metformin are less
      conclusive, thiazolidinediones appear promising. However, not all patients
      respond to thiazolidinediones. Moreover, issues related to weight gain,
      cardiovascular risk need to be addressed. The use of endocannabinoid antagonists
      and insulin secretagogues are novel strategies to combat this disorder.

PMID- 21180530
TI  - Individualizing HCV Treatment with Peginterferon and Ribavirin: What needs to be
      Done?

PMID- 21180532
TI  - Current status of therapy in nonalcoholic Fatty liver disease.
AB  - The obesity epidemic has now spread worldwide. With increase in weight, there is
      an increase in dysregulated energy metabolism ultimately leading to dysfunction
      of multiple organ systems recognized as the metabolic syndrome. Nonalcoholic
      fatty liver disease (NAFLD) is the most common form of chronic liver disease
      worldwide, and is thought to be the hepatic manifestation of metabolic syndrome.
      It is a nondiscriminating disease affecting both children and adults and no
      socioeconomic class is spared. There is a well-defined increase in both liver
      related and all-cause mortality. Current projections foresee a continued
      worsening in prevalence, especially with the increased rate of childhood obesity.
      Prevention would be the ultimate goal, but with continued trends in obesity,
      therapeutic options are needed to manage this chronic liver disease and prevent
      its complications of cirrhosis and even hepatocellular carcinoma. Therapies will
      need to be affordable, tolerable, and safe to be useful on such a large scale.
      This article will discuss some of the basic understanding of NAFLD, as well as
      review the currently tested therapies, some novel therapies, and potential future
      therapeutic options.

PMID- 21180531
TI  - Current status of therapy in autoimmune liver disease.
AB  - Therapeutic strategies for autoimmune liver diseases are increasingly
      established. Although proportionately uncommon, specialist centers have with time
      refined the best approaches for each disease, based on an improved understanding
      of the spectrum of presentation. The major treatment aims are to prevent end
      stage liver disease and its associated complications. As a result of drugs such
      as ursodeoxycholic acid, predniso(lo)ne and azathioprine, both primary biliary
      cirrhosis and autoimmune hepatitis are now less commonly indications for liver
      transplantation. Unfortunately, the same inroads in treatment efficacy have as
      yet not been made for primary sclerosing cholangitis, although the recognition
      that a subset of patients may have a treatable secondary sclerosing cholangitis
      (IgG4 related) is helping a proportion. With better biological understanding,
      more specific interventions are expected that will benefit all those with
      autoimmune liver diseases.

PMID- 21180533
TI  - Current status of therapy for hepatocellular carcinoma.
AB  - The incidence of hepatocellular carcinoma (HCC) is increasing worldwide. A multi
      disciplinary approach is required for its management. Screening high-risk
      patients allows for earlier diagnosis and the use of potentially curative
      therapies. Current recommendations for HCC screening for patients with cirrhosis
      are an abdominal ultrasound and serum alpha fetoprotein level every 6 to 12
      months. Treatment choice depends on tumor stage, liver function and the patient's
      overall functional status. Curative therapies include surgical resection, liver
      transplantation (LT), transarterial chemoembolization, and radiofrequency
      ablation (RFA). Surgical resection, either primary resection or LT, is the
      treatment most likely to result in cure of HCC. Which option to pursue is based
      on multiple factors. LT has the potential benefit of treating both HCC and the
      underlying cirrhosis; however, long wait times incur the risk of tumor
      progression. Firm recommendations regarding the role of living donor LT for HCC
      are not yet possible because of conflicting data. HCC recurrence after LT is 8
      11% and several adjuvant therapies have been investigated to reduce this.
      Bridging therapy and tumor downsizing are techniques that also may be considered
      to deal with long waiting periods and qualification for LT, respectively. If
      neither LT nor primary resection is possible, loco-regional therapies such as RFA
      and TACE should be considered. Systemic chemotherapies have proved disappointing
      for the treatment of HCC; however, newer targeted therapies such as sorafenib and
      cetuximab have provided new hope for the future.

PMID- 21180534
TI  - Eradication of H. pylori Infection: the Challenge is on if Standard Therapy
      Fails.
AB  - The recommended standard triple therapy for Helicobacter pylori infection,
      consisting of a proton pump inhibitor, clarithromycin and amoxicillin or
      metronidazole, can reach eradication rates in over 90%. However, in recent years
      resistance to antibiotics has increased and eradication rates have declined.
      Approximately one in five patients need a second-line therapy because eradication
      therapy fails. Second-line treatment with a bismuth-based quadruple therapy leads
      to satisfactory eradication rates, but bismuth is not available in many
      countries. Modern second- and third-line treatments can only be successful if
      they are adapted to the current resistance situation and they need to evolve
      continuously. Moreover, pharmacodynamic effects due to polymorphisms of the
      cytochrome P450 system are important. Because therapy adherence is significantly
      associated with therapy success, modern regimens if possible should be easy to
      take and well tolerated. In recent years, various novel salvage-therapy regimens
      have been investigated that significantly improve treatment options.

PMID- 21180535
TI  - Are We Making Progress in Preventing Barrett's-Related Esophageal Cancer?

PMID- 21180536
TI  - sPECAM-1 and sVCAM-1: Role in Pathogenesis and Diagnosis of Chronic Hepatitis C
      and Association with Response to Antiviral Therapy.
AB  - AIM: To analyze the relationship between pretreatment clinical or histological
      features and the levels of soluble platelet-endothelial cell adhesion molecule-1
      (sPECAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), to determine
      their serum concentration in responders and nonresponders, to evaluate the
      behavior under antiviral therapy, to explain their relationship in response to
      therapy and to assess the association between these two molecules in chronic
      hepatitis C (CHC). METHODS: The study analyzed 65 CHC patients, including 50
      patients (Group 1) with marked fibrosis treated with peginterferon plus
      ribavirin, 15 patients without fibrosis (Group 2) and 13 healthy volunteers (the
      control group, Group 3). sPECAM-1 and sVCAM-1 levels were assessed by an
      immunoenzymatic method (ELISA) before and after therapy. RESULTS: sVCAM-1 and
      sPECAM-1 serum concentrations increased significantly in CHC patients (p<001).
      sPECAM-1 levels corresponded to inflammatory grade (p = 0.03) and fibrosis stage
      (p =0.01). sVCAM-1 increased only in advanced fibrosis. After therapy, sPECAM-1
      levels decreased significantly (p<001) with no difference between responders and
      nonre-sponders. sPECAM-1 correlated positively with inflammatory activity (p =
      0.02), fibrosis stage (p<001), sVCAM-1 (r=0.56, p<001) and alanine
      aminotransferase activity (r = 0.30, p = 0.05). Receiver operating characteristic
      curve analysis showed a good discriminant power of serum sPECAM-1 concentrations
      for detection of liver fibrosis - stage 0 versus stage 1-3, AUC 0.81; cut-off
      221.0 ng/ml and a fair discriminant power for distinguishing bridging fibrosis,
      AUC 0.78; cut-off 237.1 ng/ml. CONCLUSIONS: Hepatitis C virus (HCV) infection
      results in upregulation of sPECAM-1 and sVCAM-1. sPECAM-1 levels are related to
      necroinflammatory activity and may also identify patients with advanced fibrosis.
      The sPECAM-1 value was decreased by therapy but its measurement cannot predict
      therapy outcome and confirm HCV persistence. sPECAM-1 may influence VCAM-1
      expression.

PMID- 21180537
TI  - Rapid virological response to peginterferon alfa and ribavirin treatment of
      chronic hepatitis C predicts sustained virological response and relapse in
      genotype 1 patients.
AB  - The treatment of chronic hepatitis C is a rapidly changing arena with new
      medications, new guidelines, and an evolving understanding of the virus, host
      factors and natural history. With the explosion of new information, the
      educational infrastructure to update clinicians has been outpaced; many feel
      uncertain if the tools they are using to care for patients are meeting the
      standard of practice. This review focuses on the most common genotype of the
      hepatitis C virus and the rules of engagement when treating with pegylated
      interferon and ribavirin. Viral assessment guideposts are evaluated and put into
      context for a clinical audience. The expected arrival of newer antiviral
      therapies is still years away, and maximizing the current treatment regimens is
      of utmost importance to eradicate virus when feasible, while minimizing toxicity.

PMID- 21180538
TI  - Ulcerative colitis: current treatment strategies and future prospects.
AB  - Ulcerative colitis (UC) is a disease of unknown etiology characterized by
      inflammation of the mucosa and occasionally the submucosa of the colon.
      Conventional drug therapy for UC involves use of aminosalicylates,
      corticosteroids, azathioprine/6-mercaptopurine, cyclosporine and anti-tumor
      necrosis factor therapy. Alternative therapies include probiotics, nicotine and
      fish oil. Drugs like tacrolimus, rosiglitazone and Trichuris suis ova are being
      evaluated for use in UC patients. With the new biologic agents, new treatment
      options for UC continue to evolve. In this article we will discuss the
      conventional drugs, the alternative therapies and the management strategies
      according to the severity and extent of UC.

PMID- 21180539
TI  - Diagnosis and management of mid-gastrointestinal bleeding by double-balloon
      endoscopy.
AB  - The new methods of capsule endoscopy (CE) and double-balloon endoscopy (DBE) have
      revolutionized the diagnostic approach to middle (mid) gastrointestinal bleeding
      (MGIB) in recent years. DBE also has therapeutic options and enables us to treat
      the MGIB endoscopically. In this review, we discuss endoscopic diagnosis and
      management of three major categories of sources of MGIB - vascular lesions,
      ulcers/erosions and tumors/polyps.

PMID- 21180540
TI  - Assessing the risks and benefits of treating Helicobacter pylori infection.

PMID- 21180541
TI  - The Effect of Metformin and Standard Therapy versus Standard Therapy alone in
      Nondiabetic Patients with Insulin Resistance and Nonalcoholic Steatohepatitis
      (NASH): A Pilot Trial.
AB  - Nonalcoholic steatohepatitis (NASH) is increasing in prevalence and is related to
      underlying insulin resistance. The aim of this study was to assess the efficacy
      of metformin on the characteristic histopathologic lesions of NASH. This was a 12
      month prospective, randomized, placebo-controlled trial comparing diet and
      exercise alone to diet, exercise and metformin in nondiabetic patients with
      insulin resistance and NASH. Patients were randomized to either group A or B.
      Group A received placebo, dietary counseling, recommendations for weight loss and
      exercise four times per week. Group B received long-acting metformin 500 mg daily
      (titrated to 1000 mg daily) plus dietary counseling, recommendations for weight
      loss and exercise four times per week. Histopathology was assessed at 12 months
      and biopsies were scored by two pathologists who were blinded to all data. Twenty
      three subjects were screened and 19 were randomized to either group A (n 1/410)
      or group B (n1/4 9). Seven of the 10 subjects in group A completed the study
      including repeat liver biopsy while all patients in group B completed the study.
      Body mass index improved in both groups decreasing by 1.7 kg/m(2) in group A and
      0.9 kg/m(2) in group B (not significant, control versus treatment). Homeostasis
      model assessment of insulin resistance scores improved in both groups decreasing
      by 1.14 in group A and 1.58 in group B (not significant, control versus
      treatment). No significant difference in histopathology was seen between groups
      on follow-up liver biopsy. Metformin appeared to have little effect in
      improvement in liver function tests or liver histology in nondiabetic patients
      with insulin resistance and NASH. Decrease in BMI through diet and exercise
      significantly improved HOMA-IR scores, serum aminotransferases and liver
      histology.

PMID- 21180542
TI  - Acute pancreatitis secondary to hemobilia after percutaneous liver biopsy.
AB  - Percutaneous liver biopsy (PLB) is a valuable diagnostic tool. Complication rates
      vary depending on the technique used, experience of the physician, number of
      passes, bleeding parameters and other factors. Hemorrhage is a common
      complication after PLB and can present as intraperitoneal bleeding, intrahepatic
      or subcapsular hematoma, or rarely as hemobilia. Acute pancreatitis is a rare
      complication of hemobilia. We describe a single case of acute pancreatitis caused
      by biliary obstruction due to hemobilia following PLB. The obstruction was
      successfully managed with biliary stent drainage.

PMID- 21180543
TI  - The challenge of developing new therapies for irritable bowel syndrome.

PMID- 21180544
TI  - Therapeutic implications of hepatitis C virus resistance to antiviral drugs.
AB  - Treatment of chronic hepatitis C is currently based on a combination of pegylated
      interferon-o! and ribavirin. Neither drug exerts direct selective pressure on
      viral functions, meaning that interferon-a/ribavirin treatment failure is not due
      to selection of interferon-a- or ribavirin-resistant viral variants. Several
      novel antiviral approaches are currently in preclinical or clinical development,
      and most target viral enzymes and functions, such as hepatitis C virus protease
      and polymerase. These new drugs all potentially select resistant viral variants
      both in vitro and in vivo, and resistance is therefore likely to become an
      important issue in clinical practice.

PMID- 21180546
TI  - Tailoring the treatment to the individual in Crohn's disease.
AB  - Crohn's disease is a heterogeneous disease with approximately 30-40% of patients
      having a simple benign history and the rest having a chronic progressive disease
      leading to complications, surgeries and potentially socio-professional
      marginalisation. Recent studies have shown that an early treatment with
      immunosuppressive treatment and/or anti-tumour necrosis factor agents could
      change the natural history of the disease and avoid the development of such
      disabling disease. The therapy should thus be tailored according to the risk of
      developing such disabling disease. Recent cohort studies have shown that clinical
      factors such as age at diagnosis, disease extent, disease location and behaviour
      at diagnosis were predictive for the development of severe or disabling disease
      and could be used in helping the physician to tailor therapy.

PMID- 21180545
TI  - The treatment of irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a highly prevalent functional bowel disorder
      routinely encountered by healthcare providers. Although not life-threatening,
      this chronic disorder reduces patients' quality of life and imposes a significant
      economic burden to the healthcare system. IBS is no longer considered a diagnosis
      of exclusion that can only be made after performing a battery of expensive
      diagnostic tests. Rather, IBS should be confidently diagnosed in the clinic at
      the time of the first visit using the Rome III criteria and a careful history and
      physical examination. Treatment options for IBS have increased in number in the
      past decade and clinicians should not be limited to using only fiber supplements
      and smooth muscle relaxants. Although all patients with IBS have symptoms of
      abdominal pain and disordered defecation, treatment needs to be individualized
      and should focus on the predominant symptom. This paper will review therapeutic
      options for the treatment of IBS using a tailored approach based on the
      predominant symptom. Abdominal pain, bloating, constipation and diarrhea are the
      four main symptoms that can be addressed using a combination of dietary
      interventions and medications. Treatment options include probiotics, antibiotics,
      tricyclic antidepressants, selective serotonin reuptake inhibitors and agents
      that modulate chloride channels and serotonin. Each class of agent will be
      reviewed using the latest data from the literature.

PMID- 21180547
TI  - Predicting response to Anti-TNF Agents for the treatment of crohn's disease.
AB  - The arrival of anti-tumor necrosis factor (TNF) agents has led to a dramatic
      improvement in the care of patients with Crohn's disease. Since these medications
      do not work in everyone, and are associated with rare, but serious side effects,
      we want to selectively treat patients who have the highest chance of responding.
      A number of variables have been studied to determine their association with
      response to anti-TNF agents. Clinical parameters include patient characteristics,
      smoking status and disease phenotype, and biologic markers include C-reactive
      protein, serum TNF levels and immune responses to microbial antigens. More
      recently, research has focused on genetics to identify polymorphisms associated
      with treatment response. Results from individual studies of these factors have
      not yet allowed for solid clinical applicability. However, further work in this
      area along with multivariate clinical prediction modeling may soon allow us to
      deliver 'personalized medicine' by predicting individualized treatment response
      in patients with Crohn's disease.

PMID- 21180549
TI  - Altering the gastrointestinal flora in patients with functional bowel disorders:
      a way ahead?
AB  - Functional gastrointestinal disorders are very common in the Western world, but
      unfortunately the underlying mechanisms behind these disorders are incompletely
      understood. Treatment options are limited and the economic consequences for
      society are profound. Recent data suggest an involvement of bacteria in the
      pathogenesis of functional gastrointestinal disorders. Probiotics are promising
      new treatment alternatives, which will be reviewed in this supplement.

PMID- 21180550
TI  - Tools for the tract: understanding the functionality of the gastrointestinal
      tract.
AB  - The human gastrointestinal tract comprises a series of complex and dynamic organs
      ranging from the stomach to the distal colon, which harbor immense microbial
      assemblages that are known to be vital for human health. Until recently, most of
      the details concerning our gut microbiota remained obscure. Over the past several
      years, however, a number of crucial technological and conceptual innovations have
      been introduced to shed more light on the composition and functionality of human
      gut microbiota. Recently developed high throughput approaches, including next
      generation sequencing technologies and phylogenetic microarrays targeting
      ribosomal RNA gene sequences, allow for comprehensive analysis of the diversity
      and dynamics of the gut microbiota composition. Nevertheless, most of the
      microbes especially in the human large intestine still remain uncultured, and the
      in situ functions of distinct groups of the gut microbiota are therefore largely
      unknown, but pivotal to the understanding of their role in human physiology.
      Apart from functional and metagenomics approaches, stable isotope probing is a
      promising tool to link the metabolic activity and diversity of microbial
      communities, including yet uncultured microbes, in a complex environment.
      Advancements in current stable isotope probing approaches integrated with the
      application of high-throughput diagnostic microarray-based phylogenetic profiling
      and metabolic flux analysis should facilitate the understanding of human
      microbial ecology and will enable the development of innovative strategies to
      treat or prevent intestinal diseases of as yet unknown etiology.

PMID- 21180551
TI  - Do Patients with Functional Gastrointestinal Disorders have an Altered Gut Flora?
AB  - The description of the de novo development of irritable bowel syndrome (IBS)
      following an episode of bacterial gastroenteritis (postinfectious IBS)
      illustrated the potential for a luminal factor (a bacterial pathogen) to cause
      this common gastrointestinal ailment. As a consequence of these and other
      observations as well as results of experiments involving animal models, the
      enteric flora and the immune response that it generates in the host have,
      somewhat surprisingly, come centre-stage in IBS research with their potential to
      induce the pathophysiological changes that are associated with IBS. While
      evidence for immune dysfunction both in the mucosa and systemically continues to
      accumulate, methodological limitations have hampered a full delineation of the
      nature of the microbiota in IBS. The latter is eagerly awaited and may yet
      provide a firm rationale for the use of certain probiotics and antibiotics in
      IBS, whose benefits have now been described with some consistency.

PMID- 21180552
TI  - Effect of probiotics on gastrointestinal function: evidence from animal models.
AB  - The digestive tract works through a complex net of integrative functions. At the
      level of the gut, this integration occurs between the immune, neuromotor and
      endocrine systems, the intestinal barrier and gut luminal contents.
      Gastrointestinal function is controlled and coordinated by the central nervous
      system to ensure effective motility, secretion, absorption and mucosal immunity.
      Thus, it is clear that the gut keeps a tightly regulated equilibrium between
      luminal stimuli, epithelium, immunity and neurotransmission in order to maintain
      homeostasis. It follows that perturbations of any of these systems may lead to
      gut dysfunction. While we acknowledge that the gut-brain axis is crucial in
      determining coordinated gut function, in this review we will focus on peripheral
      mechanisms that influence gastrointestinal physiology and pathophysiology. We
      will discuss the general hypothesis that the intestinal content is crucial in
      determining what we consider normal gastrointestinal physiology, and consequently
      that alteration in luminal content by dietary, antibiotic or probiotic
      manipulation can result in changes in gut function. This article focuses on
      lessons learned from animal models of gut dysfunction.

PMID- 21180554
TI  - Endoluminal Treatment of Barrett's Esophagus: Current and Future Prospects.
AB  - Endoluminal treatment of Barrett's esophagus has become the preferred option for
      initial intervention for advanced neoplasia without invasive carcinoma. Data from
      abstracts presented at Digestive Disease Week 2008 provide greater insight into
      optimal use of existing techniques and an early look at potential next generation
      therapies. Results from the AIM Dysplasia trial describe a larger study with
      longer post-treatment surveillance highlighting the efficacy and tolerability of
      radiofrequency ablation, while early results from liquid nitrogen cryotherapy
      studies suggest a potential to obtain similar eradication results with very high
      tolerability. Endoscopic resection, despite its risks, remains a popular option
      for focal as well as more widespread resection of Barrett's mucosa. Additional
      abstracts highlight novel approaches to ablation and resection. Enhanced imaging
      techniques and molecular marker analysis also appear to improve treatment
      outcomes. However, time and further studies of combined approaches to diagnosis
      and eradication are necessary to optimize treatment algorithms.

PMID- 21180553
TI  - Do probiotics improve symptoms in patients with irritable bowel syndrome?
AB  - There is increasing evidence that inflammation or a disturbance of the flora
      within the gut might contribute to the pathogenesis of irritable bowel syndrome
      (IBS), at least in a proportion of cases. As a consequence it has been speculated
      that, as some probiotic bacteria have a range of anti-inflammatory and
      immunomodulatory properties, the administration of such organisms might prove to
      be beneficial in this condition. It has to be acknowledged that the quality and
      design of trials of probiotics in IBS has been somewhat variable but the majority
      have shown benefit, although some bacteria appear to be more effective than
      others. More recent studies using Bifidobacterium infantis 35624 and
      Bifidobacterium lactis DN-173-010 have given particularly encouraging results.
      Issues for the future include determining which organisms are most effective,
      defining optimal doses, comparing methods of delivery and assessing the role of
      mixtures or the addition of prebiotics.

PMID- 21180555
TI  - Improving compliance with helicobacter pylori eradication therapy: when and how?
AB  - Compliance with therapy is the single most important factor in Helicobacter
      pylori (H. pylori) eradication. Poorer levels of compliance with therapy are
      associated with significantly lower levels of eradication. Numerous factors can
      contribute to achieving good levels of compliance. These include the complexity
      and duration of treatment. It is also important that the physician is motivated
      to ensure eradication is confirmed and the patient is sufficiently informed to
      empower him or her to achieve high levels of compliance. Compliance is also
      contingent on medication regimes that are simple, safe, tolerable and
      efficacious. The opportunity to improve compliance exists at every point of
      contact between the patient and the medical services. Experts and opinion leaders
      in the field can play a role by ensuring that physicians are educated and
      motivated enough to encourage and support compliance with H. pylori eradication
      therapy. Both patients and physicians need to be aware of the importance of the
      bacterium in causing disease. The importance of the doctor-patient relationship
      is paramount. Pragmatic strategies that may be of assistance may come in the form
      of polypills, combined Blister Packs, adjuvant therapies and modified release
      compounds. Colleagues such as pharmacists and nurse specialists can also play an
      important role and should be actively engaged. Structured aftercare and follow up
      offers the best chance for ensuring compliance and subsequent eradication of the
      H. pylori pathogen.

PMID- 21180556
TI  - Portopulmonary hypertension: challenges in diagnosis and management.
AB  - Portopulmonary hypertension is defined as the combination of pulmonary arterial
      hypertension with portal hypertension and presents management complications in
      patients awaiting liver transplantation. The combination of these vascular
      disorders has a marked impact on mortality. At present the recommendations for
      management are limited because of the paucity of definitive clinical trials. We
      have reviewed the available data on prevalence, diagnosis and treatment. It is
      clearly time to more formally approach the study of this patient population.

PMID- 21180559
TI  - Editorial.

PMID- 21180557
TI  - Predicting the probable outcome of treatment in HCV patients.
AB  - Hepatitis C virus (HCV) is a major cause of chronic liver disease infecting more
      than 170 million people worldwide. HCV produces a wide gamut of manifestations
      varying from mild self-limiting disease to cirrhosis and hepatocellular
      carcinoma. A variety of viral, environmental and host genetic factors contribute
      to the clinical spectrum of patients infected with HCV and influence response to
      interferon (IFN) therapy. Predicting the probable outcome of treatment in
      patients with HCV infection has always been a challenging task. Treatment of HCV
      by pegylated interferon (peg-IFN) plus ribavirin eradicates the virus in
      approximately 60% of patients - HCV genotype 1 (42-51% response rates) and
      genotypes 2 and 3 (76-84% response rates); however, a significant number of
      patients do not respond to therapy or relapse following discontinuation of
      treatment or have significant side effects that preclude further treatment.
      Accurately predicting the patients who will respond to therapy is becoming
      increasingly important, both from the point of patient care and also with respect
      to the healthcare cost as clinicians need to continue treatment in patients who
      will respond and stop treatment in patients who are unlikely to respond. Viral
      RNA measurements and genotyping are used to optimize treatment as a low viral
      load and nongenotype 1 is more likely to be associated with sustained virological
      response (SVR). Rapid virological response (RVR) defined by undetectable HCV RNA
      at 4 weeks of treatment is increasingly being recognized as a powerful tool for
      predicting treatment response. A variety of host factors including single nuclear
      polymorphisms (SNPs) of IFN response genes, insulin resistance, obesity,
      ethnicity, human leukocyte antigens and difference in T-cell immune response has
      been found to modulate the response to antiviral treatment. The presence of
      severe fibrosis/cirrhosis on pretreatment liver biopsy predicts a poor response
      to treatment. Recent studies on gene expression profiling and characterization of
      the liver and serum proteome provide options to accurately predict the outcome of
      patients infected with HCV in the future. Future studies on the factors that
      predict treatment response and tailoring treatment based on this is required if
      we are to conquer this disease.

PMID- 21180558
TI  - New and developing therapies for celiac disease.
AB  - The treatment for celiac disease, a removal of gluten in the diet, is safe and
      effective for the vast majority of patients. There is a large body of evidence
      that the diagnosis and treatment of those with celiac disease ensures
      considerable health benefits. Although a gluten-free diet is the principal
      treatment for celiac disease, it is relatively expensive, inconvenient and
      difficult to adhere to. For these reasons, there is interest in developing
      alternative therapies. Emerging research for the treatment of celiac disease has
      focused on three areas: to decrease gluten exposure, to modify intestinal
      permeability and to modulate immune activation. Therapies developed thus far
      consist of enzymes designed to digest gluten and the use of inhibitors of
      paracellular permeability to decrease the migration of gluten peptides into the
      lamina propria. Other potential therapeutic maneuvers include the binding of
      gluten by polymers, the use of tissue transglutaminase (TTG) inhibitors and DQ2
      or DQ8 blockers, or modulation of cytokine production. While all represent new
      and exciting therapies, an ideal therapy should have virtually no side effects
      similar to a gluten-free diet. A pharmaceutical agent may be used on an
      intermittent basis, such as following occasional gluten exposure or on a chronic
      basis to mitigate the effects of potential inadvertent ingestion of gluten.

PMID- 21180560
TI  - Treatment of neuromyelitis optica: current debate.
AB  - Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that largely
      affects optic nerves and spinal cord. Recent studies have identified an elevation
      of serum anti-aquaporin 4 antibody as a hallmark of NMO. Typical cases of NMO
      significantly differ from multiple sclerosis (MS) in immunological markers,
      histopathology, and responses to therapy. In fact, plasma exchange may be more
      efficacious for NMO than MS, whereas interferon-beta is recommended for MS but
      not for NMO. An emerging idea that pathogenesis of NMO may involve an interaction
      of the newly identified helper T cell subset, Th17, with B cells offers potential
      targets of therapy.

PMID- 21180562
TI  - What are the Therapeutic Advances in Neurology? Opinions from World Experts.

PMID- 21180561
TI  - Is levetiracetam different from other antiepileptic drugs? Levetiracetam and its
      cellular mechanism of action in epilepsy revisited.
AB  - Levetiracetam (LEV) is a new antiepileptic drug that is clinically effective in
      generalized and partial epilepsy syndromes as sole or add-on medication.
      Nevertheless, its underlying mechanism of action is poorly understood. It has a
      unique preclinical profile; unlike other antiepileptic drugs (AEDs), it modulates
      seizure-activity in animal models of chronic epilepsy with no effect in most
      animal models of acute seizures. Yet it is effective in acute in-vitro 'seizure'
      models. A possible explanation for these dichotomous findings is that LEV has
      different mechanisms of actions, whether given acutely or chronically and in
      'epileptic' and control tissue. Here we review the general mechanism of action of
      AEDs, give an updated and critical overview about the experimental findings of
      LEV's cellular targets (in particular the synaptic vesicular protein SV2A) and
      ask whether LEV represents a new class of AED.

PMID- 21180565
TI  - Challenges in developing new multiple sclerosis therapies.

PMID- 21180563
TI  - Recent and future advances in the treatment of status epilepticus.
AB  - Status epilepticus (SE) is one of the most frequent neurological emergencies with
      an incidence of 20/100,000 per year and a mortality between 3% and 40% depending
      on etiology, age, SE type and duration. Generalized convulsive forms of SE
      (GTCSE), in particular, require aggressive treatment. Presently, only 55-80% of
      cases of GTCSE are controlled by initial therapy. Therefore, there is a need for
      new options for the treatment of SE. Here we review the current standard
      treatment including recent advances and provide a summary of preclinical and
      clinical data regarding treatment options which may become available in the near
      future. The initial treatment of SE usually consists of a benzodiazepine
      (preferably lorazepam 0.1 mg/kg) followed by phenytoin or fosphenytoin or
      valproic acid (where approved for SE therapy). With intravenous formulations of
      levetiracetam, available since 2006, and lacosamide, which is expected for autumn
      of 2008, new treatment options have become available, that should be evaluated in
      prospective controlled trials. If SE remains refractory, the induction of general
      anaesthesia using propofol, midazolam, thiopental, or pentobarbital is warranted
      in GTCSE.

PMID- 21180564
TI  - Innovative monoclonal antibody therapies in multiple sclerosis.
AB  - The recent years have witnessed great efforts in establishing new therapeutic
      options for multiple sclerosis (MS), especially for relapsing-remitting disease
      courses. In particular, the application of monoclonal antibodies provide
      innovative approaches allowing for blocking or depleting specific molecular
      targets, which are of interest in the pathogenesis of MS. While natalizumab
      received approval by the US Food and Drug Administration and the European
      Medicines Agency in 2006 as the first monoclonal antibody in MS therapy,
      rituximab, alemtuzumab, and daclizumab were successfully tested for relapsing
      remitting MS in small cohorts in the meantime. Here, we review the data available
      from these recent phase II trials and at the same time critically discuss
      possible pitfalls which may be relevant for clinical practice. The results of
      these studies may not only broaden our therapeutic options in the near future,
      but also provide new insights into disease pathogenesis.

PMID- 21180566
TI  - Diagnosis and treatment of paroxysmal dyskinesias revisited.
AB  - Paroxysmal dyskinesias (PDs) are a rare group of hyperkinetic movement disorders
      mainly characterized by their episodic nature. Neurological examination may be
      entirely normal between the attacks. Three main types of PDs can be distinguished
      based on their precipitating events - (i) paroxysmal kinesigenic dyskinesias
      (PKD), (ii) paroxysmal non-kinesigenic dyskinesias (PNKD) and (iii) paroxysmal
      exercise-induced (exertion-induced) dyskinesias (PED). The diagnosis of PDs is
      based on their clinical presentation and precipitating events. Substantial
      progress has been made in the field of genetics and PDs. Treatment options mainly
      include anticonvulsants and benefit of treatment is depending on the type of PD.
      Most important differential diagnosis are non-epileptic psychogenic, non
      epileptic organic and epileptic attack disorders, especially nocturnal frontal
      lobe epilepsy.

PMID- 21180568
TI  - Progress in the treatment of myasthenia gravis.
AB  - Substantial therapeutic progress has been made in myasthenia gravis (MG) even
      before the era of molecular medicine. Here we characterize modern treatment
      algorithms that are adapted to disease severity and introduce the principle of
      escalating treatment strategies for MG. In very mild cases and in some ocular
      forms of MG, treatment with acetylcholinesterase inhibitors may be sufficient, at
      least temporarily, but commonly some kind of immunologically active treatment is
      needed. In generalized MG, a wide array of immunosuppressive treatments has been
      established through observational studies, some prospective, but most of them
      have never been tested in a double-blind, prospective and randomized trial.
      Within the immunologically active drugs, glucocorticosteroids (GCS) and the
      immunosuppressive drug azathioprine (Aza) have been studied the longest. Aza is
      still the standard base-line treatment, in particular in cases where high doses
      of GCS would be needed to maintain remission. If Aza is not tolerated, several
      alternatives are available including cyclosporine A (Cic A), mycophenolate
      mofetil, cyclophosphamide, and methotrexate, all of them off-label in most
      western countries. Tacrolimus is under investigation. More severe cases may
      profit from drug combinations in which compounds with more rapidly acting drugs
      (GCS, Cic A) are combined with others showing a more delayed action (Aza). All
      such combination therapies need to be supervised by an experienced
      neuroimmunological center because of potentially serious adverse reactions.
      Serial measurements of anti-acetylcholine receptor antibodies, once these are
      elevated, is a useful adjunct for monitoring long-term treatment success and may
      help in weaning from higher to lower doses or to single drugs rather than
      combinations. For very severe and treatment-resistant cases, co-treatment with
      intravenous immunoglobulins or different modalities of plasmapheresis may be
      considered on the short term while the humanized monoclonal anti-CD 20 antibody
      (rituximab) is a candidate for the long term. In highly refractory cases also
      immuno-ablation via high-dose cyclophosphamide, followed by hematologic trophic
      factors such as G-CSF, has been tried successfully. Future developments may
      include other immunologically active monoclonal antibodies (e.g., anti-CD 52,
      Campath-1). Up to 10% of patients with MG are associated with a malignant
      thymoma, often referred to as paraneoplastic MG, as detected by CT scan or MRI,
      and these patients require thymomectomy and sometimes postsurgical chemotherapy
      and radiation treatment. In nonthymoma patients with generalised MG, including
      older children and adults up to the 5th decade, a complete transsternal
      thymectomy is recommended based on available open trials and expert opinion,
      preferentially during the first year of disease. Endoscopic surgery may also be
      effective. Before surgery, pretreatment with immunosuppressive medication or
      plasmapheresis is usually recommended to ameliorate MG and subsequently reduce
      perioperative morbidity and mortality which is now near zero in experienced
      centers. Myasthenic crisis is the life-threatening exacerbation of MG and is best
      treated by plasmapheresis, mostly combined with immunoadsorption techniques.
      Intravenous immunoglobulins are a reasonable alternative, but a shortage in
      supplies and high prices limit its use.

PMID- 21180567
TI  - Therapeutic applications of hypothermia in cerebral ischaemia.
AB  - There is considerable experimental evidence that hypothermia is neuroprotective
      and can reduce the severity of brain damage after global or focal cerebral
      ischaemia. However, despite successful clinical trials for cardiac arrest and
      perinatal hypoxia-ischaemia and a number of trials demonstrating the safety of
      moderate and mild hypothermia in stroke, there are still no established
      guidelines for its use clinically. Based upon a review of the experimental
      studies we discuss the clinical implications for the use of hypothermia as an
      adjunctive therapy in global cerebral ischaemia and stroke and make some
      suggestions for its use in these situations.

PMID- 21180569
TI  - New advances in the treatment of neurological diseases using high dose
      intravenous immunoglobulins.
AB  - Since the incidental discovery in 1981 that intravenous immunoglobulins (IVIg)
      are immunomodulatory, they have been investigated in a large number of putative
      autoimmune diseases. This has led to licensing for idiopathic thrombocytopenic
      purpura, Kawasaki disease, and in neurological disorders for Guillain-Barre
      syndrome (GBS). Although not licensed, randomized controlled trials have also
      shown IVIg efficacy in other neuroimmunological diseases such as multifocal motor
      neuropathy (MMN), chronic inflammatory demyelinating neuropathy (CIDP),
      myasthenia gravis, dermatomyositis, and stiff-person syndrome. However, other
      indications are currently being explored including Alzheimer's disease, postpolio
      syndrome, and narcolepsy. There are even reports from experimental studies in
      stroke. The results of recently published clinical trials in both the classical
      neuroimmunological disorders as well as for new indications are reported and
      their role in clinical practice is discussed.

PMID- 21180572
TI  - Natalizumab: benefit outweighs risk in selected patients with multiple sclerosis.

PMID- 21180573
TI  - Natalizumab: Increased Vigilance is Required in Treating Patients with Multiple
      Sclerosis.

PMID- 21180570
TI  - Neutralizing antibodies against interferon-Beta.
AB  - The development of neutralizing antibodies (NAbs) is a major problem in multiple
      sclerosis (MS) patients treated with interferon-beta (IFN-beta). Whereas binding
      antibodies (BAbs) can be demonstrated in the vast majority of patients, only a
      smaller proportion of patients develop NAbs. The principle in NAb in vitro assays
      is the utilization of cultured cell lines that are responsive to IFN-beta. The
      cytopathic effect (CPE) assay measures the capacity of NAbs to neutralize IFN-
      beta's protective effect on cells challenged with virus and the MxA induction
      assay measures the ability of NAbs to reduce the IFN-beta-induced expression of
      MxA, either at the mRNA or the protein level. A titer of >20 neutralizing
      units/ml traditionally defines NAb posi-tivity. NAbs in high titers completely
      abrogate the in vivo response to IFN-beta, whereas the effect of low and
      intermediate titers is unpredictable. As clinically important NAbs appear only
      after 9-18 months IFN- beta0 therapy, short-term studies of two years or less are
      unsuitable for evaluation of clinical NAb effects. All long-term trials of three
      years or more concordantly show evidence of a detrimental effect of NAbs on
      relapses, disease activity on MRI, or on disease progression. Persistent high
      titers of NAbs indicate an abrogation of the biological response and, hence,
      absence of therapeutic efficacy, and this observation should lead to a change of
      therapy. As low and medium titers are ambiguous treatment decisions in patients
      with low NAb titres should be guided by determination of in vivo mRNA MxA
      induction and clinical disease activity.

PMID- 21180574
TI  - Therapeutic advances and future prospects in immune-mediated inflammatory
      myopathies.
AB  - THE INFLAMMATORY MYOPATHIES INCLUDE THREE DISTINCT ENTITIES: polymyositis (PM),
      dermatomyositis (DM), and inclusion body myositis (IBM). A T-cell-mediated
      cytotoxic process in PM and IBM and a complement-mediated microangiopathy in DM
      are the hallmarks of the underlying autoimmune processes. The most consistent
      therapeutic problem remains the distinction of PM from the difficult-to-treat
      mimics such as s-IBM, necrotizing myopathies and inflammatory dystrophies. This
      review provides a step-by-step approach to the treatment of inflammatory
      myopathies, highlights the common pitfalls and mistakes in therapy, and
      identifies the emerging new therapies. In uncontrolled studies, PM and DM respond
      to prednisone to some degree and for some period of time, while a combination
      with one immu-nosuppressive drug (azathioprine, cyclosporine, mycophenolate,
      methotrexate) offers additional benefit or steroid-sparing effect. In contrast,
      IBM is resistant to most of these therapies, most of the time. Controlled studies
      have shown that IVIg is effective and safe for the treatment of DM, where is used
      as a second, and at times first, line therapy. IVIg seems to be also effective in
      the majority of patients with PM based on uncontrolled series, but it offers
      transient help to a small number of patients with IBM especially those with
      dysphagia. Bona fide patients with PM and DM who become resistant to the
      aforementioned therapies, may respond to rituximab, tacrolimus or rarely to an
      tumor necrosis factor alpha inhibitor. For IBM patients, experience with
      alemtuzumab, a T-cell-depleting monoclonal antibody, is encouraging.

PMID- 21180575
TI  - Future Perspectives for Brain Pharmacotherapies: Implications of Drug Transport
      Processes at the Blood-brain Barrier.
AB  - Years ago, ischemic stroke was regarded as a model disease for the development of
      neuroprotective therapies by the pharmacological industry. Results were
      disappointing. There are still no treatments available allowing the rescue of
      brain tissue once a stroke has occurred. Study failure is not only a problem in
      the stroke field. In other neurodegenerative conditions and in non-degenerative
      brain disorders, progress in drug development was also rather scarce until
      recently. An important factor in drug failure is the blood-brain barrier, which
      expresses active transporters that eliminate drugs from the brain. These
      transporters exhibit strong variations between different animals, which make it
      difficult to predict brain concentrations of drugs over species barriers. This
      paper claims that more detailed knowledge about: (1) the biology of blood-brain
      barrier transporters; (2) their regulation in brain disease, (3) the affinity of
      transporters to candidate drugs; and (4) the accumulation of drugs in brain
      tissue is needed for the overall success of clinical trials to be improved. An
      alternative strategy could be the use of disease-modifying treatments that do not
      have to enter the brain to exert their function. As such, restorative and anti
      inflammatory strategies acting at the blood-brain interface might gain
      therapeutic potential in the future.

PMID- 21180576
TI  - Escalating immunotherapy of multiple sclerosis.
AB  - Basic disease-modifying treatment for relapsing forms of active multiple
      sclerosis (MS) is now available in many countries with high prevalence rates, for
      this chronic inflammatory disease of the central nervous system. Several lines of
      evidence support early immunomodulatory treatment with either recombinant
      interferon-beta or glatiramer acetate, and positive results from phase III trials
      encourage start of treatment even in patients with clinically isolated syndromes
      (CIS). However, currently available drugs for basic therapy are only partially
      effective and patients may still encounter relapses or disease progression. As
      treatment-refractory, clinically active MS can quickly lead to irreversible
      neurological disability there is an urgent need for effective escalating
      strategies. Patients with suboptimal treatment response to basic therapy have
      been treated with combination therapies, cytotoxic drugs (such as mitoxantrone
      and cyclophosphamide) or autologous hematopoietic stem cell transplantation.
      Recently, the monoclonal antibody, natalizumab, was added to this armamentarium.
      None of these strategies have been vigorously evaluated in large randomized,
      controlled phase III trials with patients who failed basic therapy. Therefore,
      the decision to escalate immunotherapy is still based on limited evidence. This
      article will review potential candidates for intensified immunosuppression and
      call for innovative study designs to better evaluate escalating immunotherapy in
      MS.

PMID- 21180579
TI  - Sequential Therapy for Helicobacter Pylori Eradication: The Time is Now!

PMID- 21180577
TI  - Recombinant Human Erythropoietin: Novel Strategies for Neuroprotective/Neuro
      regenerative Treatment of Multiple Sclerosis.
AB  - Treatment of multiple sclerosis (MS) is still unsatisfactory and essentially non
      existing for the progressive course of the disease. Recombinant human
      erythropoietin (EPO) may be a promising neuroprotective/neuroregenerative
      treatment of MS. In the nervous system, EPO acts anti-apoptotic, antioxidative,
      anti-inflammatory, neurotrophic and plasticity-modulating. Beneficial effects
      have been shown in animal models of various neurological and psychiatric
      diseases, including different models of experimental autoimmune
      encephalomyelitis. EPO is also effective in human brain disease, as shown in
      double-blind placebo-controlled clinical studies on ischemic stroke and chronic
      schizophrenia. An exploratory study on chronic progressive MS yielded lasting
      improvement in motor and cognitive performance upon high-dose long-term EPO
      treatment.

PMID- 21180580
TI  - Endoscopic Resection with Ligation Using a Multi-Band Mucosectomy System in
      Barrett's Esophagus with High-Grade Dysplasia and Intramucosal Carcinoma.
AB  - BACKGROUND: Endoscopic therapy for early neoplasia in Barrett's esophagus (BE) is
      evolving. Endoscopic resection has an increasing role. We wanted to evaluate the
      safety and efficacy of multi-band ligation/resection [ER-L] without pre-injection
      in BE with high-grade dysplasia [HGD] and intramucosal carcinoma [IMCA]. METHODS:
      A cohort of 65 consecutive patients from a single academic medical center, who
      underwent ER-L as part of endoscopic eradication therapy for BE with HGD/IMCA
      were studied. ER-L was performed afterendoscopic mapping and endoscopic
      ultrasound (EUS). Subsequently, adjunctive ablative therapies including
      photodynamic therapy, argon plasma coagulation and radiofrequency ablation were
      applied to achieve complete eradication of all BE. Thereafter biopsy surveillance
      was performed per protocol. All patients were prescribed a proton-pump inhibitor.
      MAIN OUTCOME MEASUREMENTS: Change in histopathological stage; eradication of BE
      and HGD/IMCA; adverse events. RESULTS: The median number of ER-L applications in
      each session was 4 (range 1-6) and the mean total number of ER-L sessions was
      1.5. Compared with prior forceps biopsy, histopathology from the ER-L specimen
      changed in 24 (37.5%, p = <0.0001). With median follow-up of 15 months (range 8
      42), complete and durable BE eradication was achieved with ER-L alone in 36 (60%)
      and the remainder with adjunctive ablation therapies. There were nine
      complications (four (6%) acute bleeding, five (7.5%) strictures, zero
      perforations). CONCLUSIONS: ER-L without submucosal (SM) pre-injection is safe
      and effective when applied selectively for eradication of BE with HGD/IMCA. There
      is significant change in pathological stage after ER-L conferring a diagnostic
      and staging advantage. ER-L may be used adjunctively with ablation therapies.

PMID- 21180582
TI  - Advances in the diagnosis and treatment of small bowel lesions with Crohn's
      disease using double-balloon endoscopy.
AB  - With the recent development of double-balloon endoscopy (DBE) and capsule
      endoscopy (CE), it has become possible to observe the entire small bowel
      endoscopically. DBE enables us to make detailed observations and at the same time
      takes biopsy samples. Single-balloon endoscopy (SBE), which has a balloon only at
      the tip of the overtube, has also been introduced. Since DBE and SBE are similar
      in the concept of insertion method, a general term 'balloon-assisted endoscopy'
      (BAE) is used when referring to these methods. Characteristic small bowel lesions
      observed with BAE in Crohn's disease are aphthoid ulcers, round ulcers, irregular
      ulcers and longitudinal ulcers. These ulcers tend to be located on the mesenteric
      side of the small bowel. Since BAE can determine the location (mesenteric or
      antimesenteric side) of the ulceration, it is useful in distinguishing Crohn's
      disease from other diseases that have ulcers in the small bowel. Strictures are a
      major clinical problem in the course of Crohn's disease. Traditionally, surgery
      was the main choice for small bowel strictures. In some cases, strictures located
      in distal ileum or proximal jejunum have been dilated using standard
      enteroscopes. DBE now enables balloon dilatation to be performed endoscopically
      even in the deep small bowel.

PMID- 21180581
TI  - Second-line rescue therapy of helicobacter pylori infection.
AB  - Helicobacter pylori infection is the main known cause of gastritis,
      gastroduodenal ulcer disease and gastric cancer. After more than 20 years of
      experience in H. pylori treatment, however, the ideal regimen to treat this
      infection has still to be found. Nowadays, apart from having to know well first
      line eradication regimens, we must also be prepared to face treatment failures.
      Therefore, in designing a treatment strategy we should not focus on the results
      of primary therapy alone, but also on the final (overall) eradication rate. The
      choice of a 'rescue' treatment depends on which treatment is used initially. If a
      first-line clarithromycin-based regimen was used, a second-line metronidazole
      based treatment (quadruple therapy) may be used afterwards, and then a
      levofloxacin-based combination would be a third-line 'rescue' option.
      Alternatively, it has recently been suggested that levofloxacin-based 'rescue'
      therapy constitutes an encouraging second-line strategy, representing an
      alternative to quadruple therapy in patients with previous PPI-clarithromycin
      amoxicillin failure, with the advantage of efficacy, simplicity and safety. In
      this case, quadruple regimen may be reserved as a third-line 'rescue' option.
      Finally, rifabutin-based 'rescue' therapy constitutes an encouraging empirical
      fourth-line strategy after multiple previous eradication failures with key
      antibiotics such as amoxicillin, clarithromycin, metronidazole, tetracycline, and
      levofloxacin. Even after two consecutive failures, several studies have
      demonstrated that H. pylori eradication can finally be achieved in almost all
      patients if several 'rescue' therapies are consecutively given. Therefore, the
      attitude in H. pylori eradication therapy failure, even after two or more
      unsuccessful attempts, should be to fight and not to surrender.

PMID- 21180583
TI  - Management of the returning traveler with diarrhea.
AB  - Traveler's diarrhea (TD) strikes 20-60% of travelers visiting developing
      countries. It occurs shortly after the return and can be distinguished into two
      categories: acute and persistent TD. Acute TD, mostly caused by bacterial and
      viral pathogens, is usually mild and self-limited, and deserves empirical
      symptomatic and/or antibiotic therapy in selected cases. Fluoroquinolones are
      progressively superseded in this indication by azithromycin, a well tolerated
      macrolide active against most bacteria responsible for TD, including the
      quinolone-resistant species of Campylobacter jejuni that are now pervasive,
      especially in Southeast Asia and India. Persistent TD in the returning traveler
      is much rarer than its acute counterpart and may be associated with three types
      of causes. Persistent infections, among which Giardia and possibly Entamoeba
      predominate, account for a significant proportion of cases. Postinfectious
      processes represent a second cause and comprise temporary lactose malabsorption
      and postinfectious irritable bowel syndrome, now considered a major cause of
      persistent TD. Finally, apparently unrelated chronic diseases causing diarrhea
      are occasionally unmasked by TD and represent a third type of persistent TD,
      among which the well established case of incident inflammatory bowel disease
      poses intriguing pathogenesis questions. This review discusses recent advances in
      the field and provides practical recommendations for the management of TD in
      adult, immunocompetent returning travelers.

PMID- 21180585
TI  - Possible interactions between dietary fibres and 5-aminosalicylic acid
      [corrected].
AB  - BACKGROUND: Potentially, a binding of 5-aminosalicylic acid (5-ASA) to dietary
      fibres could reduce the systemic absorption and increase the intraluminal amount
      [corrected]. The purposes of the study were to investigate if: (1) dietary fibres
      can bind 5-ASA in vitro, and (2) consumption of dietary fibres is related to
      disease activity in patients with ulcerative colitis (UC) treated with 5-ASA.
      METHODS: In vitro: 15 g of Ispaghula Husk, wheat bran, citrus-pectin, or wheat
      flour were incubated in a 37 degrees C buffered solutions of 5-ASA (1 g/l) for 3
      hours at pH 6 and 7. The concentrations of 5-ASA were determined before and after
      the incubation using HPLC. In vivo: patients with UC were interviewed two to
      three times during 6 months. The fibre consumption was estimated and related to
      the disease activity (CAI, CRP, Faecal-calprotectin) and quality of life (IBDQ).
      RESULTS: In vitro: 5-ASA was bound to Ispaghula Husk (5.3-10.0 mg/g) and wheat
      bran (4.6-5.5 mg/g), and to a minor degree to citrus-pectin. No differences were
      found in relation to pH. In vivo: 29 patients completed the scheduled interviews.
      No significant changes in fibre consumption were observed over time; however,
      patients consuming a diet high in fibre (>20 g/day) had significantly lower CRP
      (p <0.01) and faecal-calprotectin (p <0.01) than those consuming less fibre (<20
      g/dg). CONCLUSIONS: Patients with a high intake of fibre had a lower disease
      activity than those with low intake. Ispaghula Husk bound 5-ASA in vitro,
      independent of pH. The effect might be clinically relevant in patients with UC
      treated with 5-ASA.

PMID- 21180586
TI  - A clinical guide to using intravenous proton-pump inhibitors in reflux and peptic
      ulcers.
AB  - Intravenous (IV) proton-pump inhibitors (PPIs) are potent gastric acid
      suppressing agents, and their use is popular in clinical practice. Both IV and
      oral PPIs have similarly short half-lives, and their effects on acid secretion
      are similar, thus their dosing and dosage intervals appear to be interchangeable.
      The possible exception is when sustained high pHs are required to promote clot
      stabilization in bleeding peptic ulcers. Continuous infusion appears to be the
      only form of administration that reliably achieves these high target pHs. IV PPI
      is indicated in the treatment of high-risk peptic ulcers, complicated
      gastroesophageal reflux, stress-induced ulcer prophylaxis, Zollinger-Ellison
      syndrome, and whenever it is impossible or impractical to give oral therapy. The
      widespread use of PPIs has been controversial. IV PPIs have been linked to the
      development of nosocomial pneumonia in the intensive care setting and to
      spontaneous bacterial peritonitis in cirrhotic patients. This review discusses
      the use of IV PPI in different clinical scenarios, its controversies, and issues
      of appropriate use.

PMID- 21180587
TI  - Oral administration of Alequel, a mixture of autologous colon-extracted proteins
      for the treatment of Crohn's disease.
AB  - The pathogenesis of Crohn's disease involves an immune-mediated damage to the gut
      mucosa. Current developed therapies are based on the use of immunosuppressive
      drugs that can lead to significant drug-related adverse responses. There is a
      need for a therapeutic strategy that is more specific and less global in its
      effect on the immune system. Oral tolerance is an active process wherein oral
      administration of antigens is associated with the induction of regulatory cells
      and the suppression of effector cells directed toward specific and nonspecific
      antigens. Studies in animal models of experimental colitis suggest that oral
      administration of proteins extracted from the gut can induce tolerance and
      alleviate the disease symptoms. Recent clinical trials showed that oral
      administration of Alequel, an autologous protein-containing colon extract, to
      patients with Crohn's disease is safe and may be effective as a therapeutic
      modality for treating the disease. This treatment was associated with disease
      associated antigen alterations of the immune response in the patients. Oral
      administration of Alequel could provide a patient-tailored approach that is side
      effect-free for the treatment of patients with Crohn's disease.

PMID- 21180588
TI  - Immunomodulators for all patients with inflammatory bowel disease?
AB  - Recent insight into the pathogenesis of Crohn's disease (CD) and ulcerative
      colitis (UC) have led to the development of new treatment options, with a
      progressive shift to more evidence-based strategies based on sound
      pathophysiological rationales. A better understanding of inflammatory bowel
      disease (IBD) pathophysiology has progressively resulted in a more frequent use
      of immunomodulators. We review the recommended or suggested use of conventional
      immunomodulators such as azathioprine, 6-mercaptopurine, methotrexate in the
      treatment of IBD. Moreover, an effort is made to explore some critical areas in
      which early and more diffuse use of these agents may be advocated.

PMID- 21180589
TI  - Hepatitis C virus replication and potential targets for direct-acting agents.
AB  - We finally stand at the brink of novel, oral, direct-acting antivirals for the
      treatment of hepatitis C virus (HCV) infection. Basic science research has lead
      to a greater understanding of the viral life cycle and identified numerous
      potential targets for therapy. Early compounds were plagued by inconsistent in
      vivo activity and side effects that led to discontinuation of investigational
      efforts. However, several agents have now progressed to phase 2 human studies and
      two protease inhibitors have completed enrolment for their phase 3 clinical
      trials and look promising. Thus, while it appears that protease inhibitors will
      likely be the next available drugs for the treatment of HCV infection, the quest
      for additional therapeutic agents will continue. The future of HCV therapy lies
      in multidrug cocktails of several agents targeted against a variety of targets.
      In the near future these agents will be added to the current standard therapy
      consisting of pegylated interferon and ribavirin; however, the ultimate and
      probably realistic goal will be to develop multidrug oral regiments to replace
      the need for interferon.

PMID- 21180591
TI  - Oral proton-pump inhibitors and step-down therapy for nonulcer dyspepsia: is this
      the right approach?

PMID- 21180590
TI  - Hepatocellular carcinoma: review of current treatment with a focus on targeted
      molecular therapies.
AB  - The treatment of hepatocellular carcinoma (HCC) remains a challenge, with 1- and
      3-year survival rates of 20% and 5%, respectively, and a median survival of 8
      months. However, a better understanding of the pathogenesis of HCC, and advances
      in targeted molecular therapies provide physicians treating this disease with new
      hope. The treatment of HCC is multidisciplinary, requiring surgeons,
      hepatologists, interventional radiologists and oncologists. Thus, there is
      enormous potential to combine various treatment modalities to improve survival
      for patients. This review will describe what is currently known about the
      molecular pathogenesis of HCC, explore current and future treatments based on
      these pathways, and describe how these new therapies fit into existing approaches
      to HCC treatment.

PMID- 21180592
TI  - Current trends in inflammatory bowel disease: the natural history.
AB  - The description of the prognosis of inflammatory bowel disease (IBD) is based on
      systematic follow-up of population-based cohorts. A steady increase in incidence
      of IBD has occurred. The distribution of ulcerative colitis (UC) is fairly
      uniform with a preponderance of left-sided disease. One-third of Crohn's disease
      (CD) patients present with colonic disease, one-third with ileocolonic disease
      and one-third with small bowel disease. IBD is associated with extra-intestinal
      manifestations (EIMs) in up to 36% of patients. Uveitis and episcleritis are the
      most common. The cumulative probability of a relapsing course in UC is 90% after
      25 years. In CD disease behaviour varies substantially with time. At diagnosis
      behaviour is inflammatory in 70% of patients. At follow-up there is a change to
      either stricturing or penetrating disease. Most patients with CD will eventually
      require surgery. Risk factors for CD recurrence after surgery include
      penetrating/fistulizing disease behaviour, young age, short duration of disease
      before first surgery and ileocolonic disease. The incidence of colorectal cancer
      (CRC) in UC seems to be decreasing. The risk of CRC in CD seems to be equivalent
      to the risk in UC. Patients with small bowel CD are also at increased risk of
      small bowel adenocarcinoma. CD is associated with a mortality rate 20-70% higher
      than expected, whereas mortality in UC is equivalent to that of the general
      population. The improved prognosis of IBD, especially UC, could be due to a
      chemopreventive effect of the medications used. Further studies are needed to
      develop the best strategy for the reduction of mortality and cancer risk in IBD.

PMID- 21180593
TI  - Evaluation and management of dyspepsia.
AB  - Dyspepsia is a common clinical problem seen by both primary care physicians and
      gastroenterologists. Initial evaluation should focus on the identification and
      treatment of potential causes of symptoms such as gastroesophageal reflux disease
      (GERD), peptic ulcer disease, and medication side effects but also on recognizing
      those at risk for more serious conditions such as gastric cancer. This manuscript
      discusses the evaluation and management of dyspepsia including the role of proton
      pump inhibitors, treatment of Helicobacter pylori, and endoscopy. Finally,
      treatment of refractory functional dyspepsia is addressed.

PMID- 21180594
TI  - Current directions of biologic therapies in inflammatory bowel disease.
AB  - Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel
      diseases which can be difficult to control with conventional therapies. A greater
      understanding of their pathophysiology has led to new therapies that target
      specific molecules of the inflammatory cascade. Three anti-tumor necrosis factor
      (TNF) monoclonal antibodies have been developed. Infliximab and adalimumab can
      induce clinical response and sustained remission in CD. Infliximab is also
      effective in UC. Certolizumab pegol gives good short-term results but long-term
      efficacy has yet to be determined in other clinical trials. Therapies that target
      leucocyte trafficking (anti-integrins) have also been developed and are
      associated with good clinical response in CD. Natalizumab (anti-alpha4 integrin
      antibody) is associated with important side effects and is not used anymore in
      gastroenterology in Europe but is still used in the USA. Vedolizumab (MLN0002),
      an anti-alpha4beta7 integrin antibody, has a good efficacy and safety profile.
      Monoclonal antibodies targeting other cytokines are also under development. For
      example, ustekinumab (CNTO 1275) inhibits interleukins 12 and 23. It is
      associated with a good clinical response in CD.

PMID- 21180595
TI  - Efficacy and safety of tenofovir disoproxil fumarate in patients with chronic
      hepatitis B.
AB  - Chronic hepatitis B (CHB) is prevalent worldwide. It may cause cirrhosis and
      hepatocellular carcinoma. Treatment for this condition may need to be lifelong,
      thus the drugs used must be both efficacious and safe. Clinical trials of
      tenofovir have demonstrated a good safety profile for this drug and it has potent
      antiviral properties. However, to better characterize the safety of this drug,
      the postmarketing surveillance must be taken into account. Clinicians need to be
      vigilant, as infrequent adverse events may be revealed during this phase. The
      current review presents a detailed expose of preclinical and clinical data on
      tenofovir to increase awareness of possible adverse events and drug-drug
      interactions, based on the large experience of this drug in human
      immunodeficiency virus (HIV) treatment (and to date in patients with CHB).
      Several recommendations that may help the clinician to prevent the development of
      adverse events associated with tenofovir disoproxil fumarate (TDF) treatment are
      outlined, along with a suggested surveillance protocol for the timely and proper
      identification of possible renal and bone toxicity.

PMID- 21180598
TI  - Optimizing outcomes with alosetron hydrochloride in severe diarrhea-predominant
      irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal
      disorder that causes a range of symptoms. Currently, alosetron hydrochloride
      (Lotronex(r)), a selective serotonin type 3 receptor antagonist, is the only
      medication approved for the treatment of severe diarrhea-predominant irritable
      bowel syndrome (IBS-D) in women who have inadequately responded to conventional
      therapy. Alosetron has demonstrated efficacy compared with placebo in clinical
      trials and has been shown to improve overall health-related quality of life
      (HRQoL). However, rare instances of ischemic colitis and severe complications of
      constipation have been reported. As a result, in 2000 alosetron was voluntarily
      withdrawn from the market but was reintroduced in 2002 with a more restricted
      indication and a requirement that clinicians and patients follow a prescribing
      program. Although the efficacy and benefit of alosetron has been clearly
      demonstrated, it has been used sparingly since its reintroduction. This brief
      review describes the history of alosetron, efficacy of alosetron in the treatment
      of IBS, the impact of severe IBS on HRQoL, safety considerations, the risk
      evaluation and mitigation strategy program under which alosetron is now
      prescribed, and an update on postmarketing surveillance data.

PMID- 21180596
TI  - Treatment options for nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) has become increasingly recognized as
      the most common cause of abnormal liver enzymes in the last few decades and is
      among the most common forms of chronic liver disease in the Western world and
      across the globe. With the growing epidemic of obesity and diabetes, NAFLD is
      estimated to affect about one-quarter of the US population. Although most
      patients with NAFLD have nonprogressive bland steatosis, a minority of patients
      develop the histological subtype of nonalcoholic steatohepatitis (NASH), which
      may progress to cirrhosis, hepatocellular carcinoma, and liver-related death.
      This is especially true when NASH patients have type 2 diabetes. Treatment of
      NAFLD should therefore be directed towards patients with established NASH.
      Sustained weight loss seems to improve insulin resistance and associated NASH. In
      fact, weight loss with bariatric surgery leads to biochemical and histological
      improvement in morbidly obese patients with NASH. Several pharmacologic agents
      have been studied in an effort to improve insulin resistance and pro-inflammatory
      mediators potentially responsible for the development and progression of NASH.
      While some studies have shown initial promise, none has established long-term
      efficacy using randomized clinical trials. This paper briefly reviews the
      epidemiology, natural history, and pathophysiology of NAFLD and NASH and then
      focuses on the clinical trials of various therapeutic modalities for NAFLD. These
      include weight loss agents, bariatric surgery, insulin-sensitizing agents, lipid
      lowering agents, antioxidants, probiotics, anti-tumor necrosis factor agents,
      cytoprotective and other novel agents.

PMID- 21180597
TI  - Functional dyspepsia.
AB  - Dyspepsia is a common term used for a heterogeneous group of abdominal symptoms.
      Functional dyspepsia (FD) is the focus of this review. The 2006 Rome III criteria
      defined FD and its subgroups, postprandial distress syndrome (PDS) and epigastric
      pain syndrome (EPS). FD is a very common condition with a high prevalence
      throughout the world, adversely affecting the quality of life of patients. The
      pathophysiology of FD has been under investigation during the past two decades.
      Multiple mechanisms such as abnormal gastric emptying, visceral hypersensitivity,
      impaired gastric accommodation, and central nervous system factors are likely
      involved. Several tests are available for the assessment of various physiologic
      functions possibly involved in the pathogenesis of FD, and some of these could be
      used in clinical practice, helping to understand the abnormalities underlining
      patients' complaints. Currently, the possibilities of pharmacological therapy for
      FD are still limited, however, experience of using prokinetics, tricyclic
      antidepressants, selective serotonin-reuptake inhibitors (SSRIs), proton-pump
      inhibitors (PPIs), and several alternative techniques has been accumulated. The
      different combinations of alterations in physiologic gastrointestinal and central
      nervous system functions result in the very heterogeneous nature of FD so
      combined approaches to these patients could be beneficial in challenging cases.

PMID- 21180599
TI  - Anti-tumor necrosis factor therapy and influenza: keeping it in perspective.
AB  - The association of opportunistic infections in the context of anti-tumor necrosis
      factor (TNF) antibody therapies have attracted widespread attention. The recent
      H1N1 influenza pandemic brought this into sharp focus with numerous patient
      queries and physician anxieties. The following short review gives a scientific
      perspective to this issue including the role of vaccination.

PMID- 21180601
TI  - New direct-acting antivirals in the development for hepatitis C virus infection.
AB  - A large number of new therapies are in development for chronic hepatitis C
      including direct-acting antiviral drugs (DAA), which target specific hepatitis C
      virus enzymes. Two of these compounds have already advanced into phase 3
      development in the USA and EU, and many more are in phase 2 trials and likely to
      advance. In this review, the results of recent studies on ribavirin analogues,
      nonstructural (NS) 3/4 serine protease inhibitors, NS5B polymerase inhibitors,
      cyclophilin inhibitors, silimarin components, and thiazolides have been updated.
      Each compound includes a brief summary of its proposed mechanism of action,
      results of early clinical trials, and more advanced trial data where available.
      These compounds are likely to be the first approved in the USA and EU and will
      initially be used in combination with the current standard of care. It is
      possible that future treatment paradigms with these agents will offer the
      potential of interferon-free regimens. It is most likely that patients for these
      new therapies will be selected carefully by identifying and treating first those
      who have excellent sustained virologic response rates with 24 weeks of pegylated
      interferon and ribavirin, the current standard of care. It is also likely that
      there will be a need to identify those patients who are not likely to have a
      sustained virologic response with the addition of a protease inhibitor to the
      current standard of care and delaying their therapy until combination viral
      suppression therapy becomes an option. The cost and side effects of the DAA will
      be important considerations for treating physicians. This review is current
      through 2009; however, data are rapidly changing.

PMID- 21180600
TI  - Optimal use of biologics in the management of Crohn's disease.
AB  - Crohn's disease (CD) is a chronic relapsing and remitting disorder of the
      gastrointestinal tract with no known cure. The inflammation that drives the
      disease can lead to debilitating symptoms and a number of complications that may
      lead to surgery. The introduction of biologic therapy a decade ago has offered a
      new option for patients failing conventional therapy. Over time, biologic therapy
      has also led to the desire to achieve treatment goals beyond the control of
      symptoms. In order to achieve short-term and long-term goals with these new
      agents, it is important to review how these therapies may be optimized for the
      best results.

PMID- 21180602
TI  - Ulcerative colitis, infliximab, and hepatic epithelioid hemangioendothelioma: who
      is to blame? Case Report.

PMID- 21180603
TI  - Are we making progress in diagnosing and preventing gastrointestinal cancers?

PMID- 21180604
TI  - Rifaximin therapy for metronidazole-unresponsive Clostridium difficile infection:
      a prospective pilot trial.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is a recent epidemic in the
      United States, particularly in the hospital setting. Oral metronidazole is
      standard therapy for C. difficile infection, but resistance to metronidazole is
      becoming a clinical challenge. METHODS: We evaluated the efficacy of the
      nonsystemic oral antibiotic rifaximin for the treatment of metronidazole
      resistant C. difficile infection. Twenty-five patients with C. difficile
      infection were enrolled in the study. All had mild-to-moderate C. difficile
      infection (5-10 bowel movements a day without sepsis) unresponsive to
      metronidazole (i.e. stools positive for toxins A and B after oral metronidazole
      500 mg three times daily [t.i.d.] for 5 days). After discontinuation of
      metronidazole, rifaximin 400 mg t.i.d. for 14 days was prescribed. Patients were
      followed for 56 days and stool was tested for C. difficile using polymerase chain
      reaction (PCR) to assess the effect of treatment. A negative PCR test result was
      interpreted as a favorable response to rifaximin. RESULTS: Sixteen of 22 patients
      (73%) were eligible for study inclusion and completed rifaximin therapy
      experienced eradication of infection (stool negative for C. difficile)
      immediately after rifaximin therapy and 56 days post-treatment. Three patients
      (12%) discontinued therapy because of abdominal distention. Rifaximin was
      generally well tolerated. CONCLUSIONS: In conclusion, rifaximin may be considered
      for treatment of mild-to-moderate C. difficile infection that is resistant to
      metronidazole. Larger randomized trials are needed to confirm these positive
      findings.

PMID- 21180605
TI  - Diagnosis and management of Barrett's esophagus for the endoscopist.
AB  - In Barrett's esophagus, the stratified squamous epithelium lining the esophagus
      is replaced by specialized intestinal-type columnar epithelium. The prevalence of
      Barrett's esophagus has ranged from 0.9% to 4.5%. The rate of progression from
      Barrett's esophagus to esophageal adenocarcinoma is 0.5% per patient-year. Proton
      pump inhibitors are the mainstay of symptom control in Barrett's patients.
      Nondysplastic Barrett's and Barrett's with low-grade dysplasia (LGD) are
      typically managed by periodic surveillance. Radiofrequency ablation is being
      evaluated as a modality for managing nondysplastic Barrett's and Barrett's with
      LGD. The options for the management of Barrett's patients with high-grade
      dysplasia (HGD) include endoscopic therapy, surgery, and intensive surveillance
      until biopsy reveals adenocarcinoma. Endoscopic therapy involves endoscopic
      mucosal resection (EMR) and ablation. More aggressive techniques such as
      endoscopic submucosal dissection and larger segment endoscopic mucosal resection
      are under study. In this review, we discuss the diagnosis and management of
      Barrett's esophagus. The recommendations from the major gastroenterologic
      societies and the current and investigational endoscopic modalities for the
      management of Barrett's esophagus with and without dysplasia are reviewed.

PMID- 21180607
TI  - Hepatocellular carcinoma: the place of new medical therapies.
AB  - Medical therapies have entered center stage in the treatment of hepatocellular
      carcinoma (HCC) little more than a year after the positive results of a large
      phase III trial of sorafenib showed a clear survival benefit with sorafenib, a
      targeted agent, in this setting. Even though this marks a breakthrough in the
      treatment of HCC, the narrow patient profile necessary for the study to be
      successful has generated a number of questions regarding the efficacy of this
      approach in other clinical settings. New studies aiming to define the role of
      sorafenib from in the adjuvant setting, through patients with more advanced liver
      disease, all the way to combination treatments of HCC have been initiated. The
      success of one targeted drug has stimulated enormously the efforts of competitors
      to develop additional and better drugs, either in a first-line or a second-line
      setting. These are exciting times for the treatment of HCC, both for physicians
      and patients. In the years to come we will see an extension of treatment options
      in different clinical situations in patients with HCC, and survival will be
      improved in many stages of the disease, except for the most advanced. The rapid
      increase in knowledge about the molecular mechanisms underlying the development
      and progression of HCC will lead to a more tailored approach to treatment
      depending on the molecular characteristics of the tumor and the disease stage.

PMID- 21180608
TI  - Optimizing therapy with 6-mercaptopurine and azathioprine: to measure or not to
      measure?

PMID- 21180606
TI  - Anti-adhesion molecule therapy for inflammatory bowel disease.
AB  - Although biologic agents directed against tumor necrosis factor alpha (TNFalpha)
      continue to be an effective therapeutic strategy for patients with inflammatory
      bowel disease (IBD), approximately 30% of patients with Crohn's disease (CD) who
      are refractory to standard treatment do not respond to induction therapy with
      TNFalpha inhibitors and, of those who initially respond, 50% or more cease to
      respond within a year. Moreover, their use can be associated with significant
      safety issues. Clearly, there is a need to target alternative pathways involved
      in the inflammatory process. IBD is driven by the trafficking of lymphocytes from
      the circulation into the gut tissue that is mediated by adhesive interactions
      between the lymphocytes and endothelial cells. The adhesion molecules involved
      represent attractive targets for the development of new therapeutics which should
      aid in the resolution of existing inflammation, prevent recurrence of
      inflammation, and may potentially lead to long-term control of disease. In this
      article we review current opportunities and challenges facing anti-adhesion
      therapy in IBD, and discusses recent clinical development efforts that have
      focused on having an impact on two particular adhesive interactions: alpha(4)
      integrin/MAdCAM-1 and beta(2)-integrin/ICAM-1. Of particular interest is
      natalizumab, a humanized monoclonal antibody against human alpha(4) integrin that
      is approved for the treatment of patients with moderately-to-severely active CD
      and evidence of active inflammation. This agent represents an efficacious
      therapeutic option for patients who do not respond to, or have failed, a TNF
      alpha inhibitor.

PMID- 21180609
TI  - Chemopreventive effects of Coltect, a novel dietary supplement, alone and in
      combination with 5-aminosalicylic acid in 1,2-dimethylhydrazine-induced colon
      cancer in rats.
AB  - OBJECTIVES: Coltect is a novel dietary supplement containing curcumin, green tea
      and selenomethionine. Previous reports have suggested that these agents can
      prevent colorectal cancer (CRC). The present study examined the chemopreventive
      effect of Coltect alone or combined with 5-aminosalicylic acid (5-ASA) using the
      1,2-dimethylhydrazine (DMH) model in rats. METHODS: The effect of Coltect was
      examined on HT-29 CRC cells by growth inhibition assay. Apoptosis was determined
      by annexin V-FITC/PI staining. Male rats were injected with DMH in vivo and
      treated with Coltect 150 mg/kg, 5-ASA 50 mg/kg or their combination, by oral
      gavage. Aberrant crypt foci (ACF) were identified by methylene blue staining.
      RESULTS: HT-29 cells exhibited a dose-dependent response to Coltect. Part of the
      growth inhibition can be explained by the induction of mild-moderate apoptosis in
      cancer cells (28%) compared with the untreated cells (10%). In the in vivo model,
      the average number of ACF was divided into small (1-3 crypts) or large (>=4
      crypts). The Coltect compound reduced the number of small and large ACF similarly
      to 5-ASA (40% reduction). This reduction was amplified by combining the two
      agents (70% reduction). CONCLUSION: Coltect inhibits the growth of colon cancer
      cells, induces apoptosis and inhibits ACF development. Furthermore, it augments
      the growth inhibitory effect of 5-ASA in vivo. This may be clinically important
      since this safe dietary supplement-drug combination can be administered as a
      chemopreventive regimen for the treatment of CRC.

PMID- 21180610
TI  - Challenges and prospects for pharmacotherapy in functional gastrointestinal
      disorders.
AB  - Functional gastrointestinal disorders, such as irritable bowel syndrome and
      functional dyspepsia, are complex conditions with multiple factors contributing
      to their pathophysiology. As a consequence they are difficult to treat and have
      posed significant challenges to the pharmaceutical industry when trying to
      develop new and effective treatments. This review provides an overview of these
      difficulties and how the industry is reshaping its drug developmental strategies.
      It describes some of the more significant and encouraging advances that have
      occurred, and discusses how future research might embrace the opportunities
      provided by advances in genetic and in particular, epigenetic research.

PMID- 21180612
TI  - Review of the safety and efficacy of ustekinumab.
AB  - Ustekinumab is a subcutaneously and intravenously administered fully human
      monoclonal immunoglobulin (IgG1) antibody targeting the interleukin (IL)-12/23
      shared P40 subunit. The pivotal role of IL-12/23 inflammatory-mediated pathways
      is increasingly recognized in a plethora of immune-mediated inflammatory
      disorders including Crohn's disease, psoriasis, and multiple sclerosis. In a
      randomized controlled trial of ustekinumab in moderate-to-severe Crohn's disease,
      clinical response was achieved most notably in infliximab-experienced primary and
      secondary nonresponders and suboptimal responders.

PMID- 21180611
TI  - Use of probiotics in gastrointestinal disorders: what to recommend?
AB  - Perturbation of bacterial microflora of the gastrointestinal (GI) tract may play
      an important role in the pathophysiology of some GI disorders. Probiotics have
      been used as a treatment modality for over a century. They may restore normal
      bacterial microflora and effect the functioning of the GI tract by a variety of
      mechanisms. Probiotics are not currently regulated and only few randomized
      controlled trials exist investigating their efficacy in different GI disorders.
      They are available in a variety of formulations and delivery systems making
      interpretation and comparison of studies even more difficult. The efficacy of
      probiotics, either as a single strain or a combination of probiotics, has been
      tested in antibiotic-associated diarrhea, Clostridium difficile colitis,
      infectious diarrhea, ulcerative colitis, Crohn's disease, pouchitis, and
      irritable bowel syndrome, among other disorders. Results of the studies are
      reviewed in this article and recommendations for probiotic use in these disorders
      are made. Although probiotics appear to be generally safe in an outpatient
      setting, the situation may be different in immunocompromised, hospitalized
      patients who may be at a greater risk of developing probiotic sepsis. No studies
      exist addressing the issue of safety specifically. Many questions regarding use
      of probiotics in GI disorders remain to be answered in future studies, such as
      most optimal doses, duration of treatment, physiological and immunological
      effects, efficacy of specific probiotics in specific disease states, and safety
      in debilitated patients.

PMID- 21180613
TI  - The bacterial pathogenesis and treatment of pouchitis.
AB  - Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis is the
      operation of choice for patients with ulcerative colitis. Pouchitis is the most
      common cause of pouch dysfunction. Although the pathogenesis of this disease is
      not well understood, bacteria have been implicated in the disease process.
      Numerous bacterial studies have been reported over the last 25 years with few
      unifying findings. In addition, many different treatments for pouchitis have been
      reported with varying results. Antibiotic treatment remains the most studied and
      is the mainstay of treatment. In this article we review the aetiology of
      pouchitis and the evidenced-based treatment options.

PMID- 21180614
TI  - Managing bile acid diarrhoea.
AB  - Bowel symptoms including diarrhoea can be produced when excess bile acids (BA)
      are present in the colon. This condition, known as bile acid or bile salt
      malabsorption, has been under recognized, as the best diagnostic method, the
      (75)Se-homocholic acid taurine (SeHCAT) test, is not available in many countries
      and is not fully utilized in others. Reduced SeHCAT retention establishes that
      this is a complication of many other gastrointestinal diseases. Repeated studies
      show SeHCAT tests are abnormal in about 30% of patients otherwise diagnosed as
      diarrhoea-predominant irritable bowel syndrome or functional diarrhoea, with an
      estimated population prevalence of around 1%. Recent work suggests that the
      condition previously called idiopathic bile acid malabsorption (BAM) is not in
      fact due to a defect in absorption, but results from an overproduction of BA
      because of defective feedback inhibition of hepatic bile acid synthesis, a
      function of the ileal hormone fibroblast growth factor 19 (FGF19). The approach
      to treatment currently depends on binding excess BA, to reduce their secretory
      actions, using colestyramine, colestipol and, most recently, colesevelam.
      Colesevelam has a number of potential advantages that merit further investigation
      in trials directed at patients with bile acid diarrhoea.

PMID- 21180615
TI  - Chronic radiation proctitis: issues surrounding delayed bowel dysfunction post
      pelvic radiotherapy and an update on medical treatment.
AB  - Late onset bowel dysfunction post-pelvic radiotherapy is an increasingly common
      clinical scenario which is related to improved oncological treatments and cancer
      survival. 50% of patients develop bowel symptoms after pelvic radiotherapy which
      affects quality of life. Historically, bowel symptoms post-pelvic radiotherapy
      have been labelled 'chronic radiation proctitis', although it is increasingly
      recognised that these symptoms are due to dysfunction of the gastrointestinal
      (GI) tract at numerous points. The evidence-base is poor and comprises often
      small, heterogenous, single centre unblinded studies. This article critically
      reviews the evidence for the medical treatment options for 'chronic radiation
      proctitis', which include anti-inflammatory drugs, antibiotics, sucralfate,
      formalin and hyperbaric oxygen. The difficulties in extrapolation from the
      literature to clinical practise are also explored. From the available evidence,
      rectal sucralfate appears to have greater efficacy than anti-inflammatory agents,
      which are more effective if used with oral metronidazole. Furthermore, hyperbaric
      oxygen is emerging as promising treatment for radiation toxicity. However, bowel
      dysfunction post-pelvic radiotherapy is a complex clinical condition which
      reflects multi-site GI tract pathologies both related and unrelated to previous
      oncological treatments. From this review article a clear need for an adjustment
      to both diagnosis and treatment of these patients, as well as for further
      research, emerges.

PMID- 21180617
TI  - The therapeutic strategy for autoimmune pancreatitis is subject to the endoscopic
      features of the duodenal papilla.
AB  - Autoimmune pancreatitis (AIP) often presents with a swollen duodenal papilla,
      however, the clinical significance of the duodenal papilla in AIP has not been
      fully elucidated. Data have shown swollen duodenal papillae shaped like a pear
      and/or with a submucosal tumor having IgG4-bearing plasma cells.
      Immunohistopathology has potentially verified duodenal papillitis associated with
      AIP. FOXP3-positive lymphocytes are also recognized in AIP. AIP has shown
      spontaneous remission and relapse irrelevance to corticosteroid therapy. The
      results of a multivariate analysis revealed the absence of a swollen duodenal
      papilla as the only significant independent factor predictive of spontaneous
      remission in AIP cases. In addition, the results of another multivariate analysis
      revealed the presence of a swollen duodenal papilla and the presence of
      extrapancreatic lesions as the significant independent factors predictive of
      relapse in these cases. Results suggest that the lack of a swollen duodenal
      papilla is a predictive factor for spontaneous remission, and thus negates the
      need to administer corticosteroids in those AIP patients. In contrast, a swollen
      duodenal papilla and the presence of extrapancreatic lesions are risk factors for
      relapse, and those AIP patients are candidates for maintenance corticosteroid
      therapy to reduce relapse. Therefore, the therapeutic strategy such as the
      indication for corticosteroid administration is subject to the endoscopic
      features of the duodenal papilla.

PMID- 21180616
TI  - What is the role of endotherapy in chronic pancreatitis?
AB  - Chronic pancreatitis (CP) can have debilitating clinical course due to chronic
      abdominal pain, malnutrition and related complications. Medical, endoscopic and
      surgical treatment of CP should aim at control of symptoms, prevention of
      progression of the disease and correction of complications. Endoscopic management
      plays a specific role in carefully selected patients as primary interventional
      therapy when medical measures fail or in high-risk surgical candidates.
      Endotherapy for CP is utilized also as a bridge to surgery or to assess potential
      response to pancreatic surgery. In this review we address the role of endotherapy
      for the relief of obstruction of the pancreatic duct (PD) and bile duct, closure
      of PD leaks and drainage of pseudocysts in the setting of CP. In addition,
      endotherapy for relief of pancreatic pain by endoscopic ultrasound-guided celiac
      plexus block for CP is discussed.

PMID- 21180619
TI  - Long-term daclizumab therapy in relapsing-remitting multiple sclerosis.
AB  - We performed a retrospective review of side effects and clinical outcomes in
      relapsing-remitting (RR) multiple sclerosis (MS) patients receiving long-term
      treatment with daclizumab. Twelve patients with RR MS were initially treated with
      daclizumab at 1 mg/kg IV, again 14 days later and then monthly treatments
      (average duration 42.1 months). Daclizumab dose (0.85 mg/kg to 1.5 mg/kg) was
      adjusted based on clinical response. Daclizumab was generally well tolerated.
      There was a significant reduction in relapse rate and improvement in Expanded
      Disability Status Scores (EDSSs) (p < 0.0001). Long-term treatment with
      daclizumab in RR MS patients has apparent benefit that will require formal
      confirmation.

PMID- 21180620
TI  - Implementation of computer-based language therapy in aphasia.
AB  - A first step in evaluating the use of computers in language therapy for
      individuals with aphasia is to establish the treatment as active in small groups
      prior to large-scale clinical trials. The present study evaluated a comprehensive
      computer-based language therapy program in a group of eight individuals with
      chronic in aphasia varying broadly in age, time post onset and aphasia type.
      Results revealed an overall therapeutic benefit in auditory comprehension, as
      well as positive trends in functional communication. Findings suggest that
      comprehensive therapy programs may be beneficial for many individuals with
      aphasia, and computer-based therapy may be one feasible avenue of providing this
      intervention.

PMID- 21180621
TI  - A review of the use of zonisamide in Parkinson's disease.
AB  - Although zonisamide was previously only used to treat epilepsy, recently more
      applications have been forthcoming. Due to a good side effect profile, a lower
      frequency of interactions and a more comfortable posology, there are several
      studies regarding its uses in other pathologies such as migraine, neuropathic
      pain, essential tremor and various psychiatric diseases. A multicentered,
      randomized, double-blind, placebo-controlled study conducted in Japan suggested
      that zonisamide, as an add-on treatment, has efficacy in treating motor symptoms
      in patients with Parkinson's disease. In addition, other studies support the
      utility of zonisamide in other symptoms of this disease. The therapeutic doses of
      zonisamide for the treatment of Parkinson's disease are considerably lower than
      those for the treatment of epilepsy. This antiepileptic drug has been used in
      Japan for more than 15 years and so it is expected that it will be safe and well
      tolerated in patients with Parkinson's disease. However, the pharmacological
      mechanisms of the antiparkinsonian actions of zonisamide remain unclear and more
      basic investigation is warranted. The aim of this paper is to review the
      structure, mechanisms of action, pharmacokinetics and antiparkinsonian action of
      zonisamide.

PMID- 21180622
TI  - Evidence-based drug treatment in amyotrophic lateral sclerosis and upcoming
      clinical trials.
AB  - Amyotrophic Lateral sclerosis/motor neuron disease is a severe neurodegenerative
      disease characterized by upper and Lower motor neuron degeneration for which
      there is no truly effective treatment. Several therapies have shown promise in
      preclinical models of motor neuron disease; however, most of them failed in human
      studies, so that the noticeable progress in understanding the cellular mechanisms
      of motor neuron degeneration has not been matched with the development of
      therapeutic strategies to prevent disease progression or to extend survival
      longer than achieved by riluzole. We review treatment development in motor neuron
      disease and discuss the strengths and limitations of past as well as upcoming
      clinical trials.

PMID- 21180623
TI  - Menstrual migraine: therapeutic approaches.
AB  - The development of diagnostic criteria has enabled greater recognition of
      menstrual migraine as a highly prevalent and disabling condition meriting
      specific treatment. Although few therapeutic trials have yet been undertaken in
      accordance with the criteria, the results of those published to date confirm the
      efficacy of acute migraine drugs for symptomatic treatment. If this approach is
      insufficient, the predictability of attacks provides the opportunity for
      perimenstrual prophylaxis. Continuous contraceptive strategies provide an
      additional option for management, although clinical trial data are limited.
      Future approaches to treatment could explore the genomic and nongenomic actions
      of sex steroids.

PMID- 21180624
TI  - Depression in epilepsy: mechanisms and therapeutic approach.
AB  - In patients with epilepsy, mood disorders represent a frequent psychiatric
      comorbidity but they often remain unrecognized and untreated. However, comorbid
      depression may have a major impact on the quality of life of patients with
      epilepsy, sometimes even more than the seizures. Among the potential
      neurobiological and psychosocial determinants, epilepsy-related variables (age at
      onset of seizures, temporal lobe epilepsy and frequency of seizures) and the
      antiepileptic drug treatment have been associated with depression. Nonetheless,
      data on treatment strategies are still limited with a lack of controlled trials
      on the use of antidepressant drugs. Moreover, the issue of psychotropic drug
      treatment of depression in epilepsy is interlinked with that of worsening
      seizures. This paper is aimed at discussing all these subjects in the light of
      current literature on the neurobiology of depression in epilepsy.

PMID- 21180625
TI  - Pathophysiology and treatment of bacterial meningitis.
AB  - Bacterial meningitis is a medical emergency requiring immediate diagnosis and
      immediate treatment. Streptococcus pneumoniae and Neisseria meningitidis are the
      most common and most aggressive pathogens of meningitis. Emerging antibiotic
      resistance is an upcoming challenge. Clinical and experimental studies have
      established a more detailed understanding of the mechanisms resulting in brain
      damage, sequelae and neuropsychological deficits. We summarize the current
      pathophysiological concept of acute bacterial meningitis and present current
      treatment strategies.

PMID- 21180626
TI  - Identifying patient subtypes in multiple sclerosis and tailoring immunotherapy:
      challenges for the future.
AB  - The accelerating pace of technological and analytical development in the fields
      of genetic and phenotypic profiling has ushered in an era of great promise for
      multiple sclerosis (MS) research. As we continue to identify modest but
      meaningful associations to MS susceptibility, disease course, treatment response,
      and other clinical or paraclinical phenotypes, we must begin to (1) embark on the
      challenging set of studies that will integrate disparate observations into
      clinical algorithms, and (2) validate their clinical utility. Genetic data are
      receiving muchofthe attention today, but they are unlikelytobesufficienttooffer a
      personalized approach to disease management in MS. Rather, the genetic
      architecture of the disease, once uncovered, will offer a fixed platform upon
      which more dynamic molecular profiles can be assembled to deconstruct the
      structure of the patient population that we label with a diagnosis of MS. The
      tools and methods to gain insight into the heterogeneity of MS patients are
      available today; we must now realize their potential in enhancing the care of MS
      patients.

PMID- 21180627
TI  - Deep brain stimulation in Parkinson's disease.
AB  - During the last 15 years deep brain stimulation (DBS) has been established as a
      highly-effective therapy for advanced Parkinson's disease (PD). Patient
      selection, stereotactic implantation, postoperative stimulator programming and
      patient care requires a multi-disciplinary team including movement disorders
      specialists in neurology and functional neurosurgery. To treat medically
      refractory levodopa-induced motor complications or resistant tremor the preferred
      target for high-frequency DBS is the subthalamic nucleus (STN). STN-DBS results
      in significant reduction of dyskinesias and dopaminergic medication, improvement
      of all cardinal motor symptoms with sustained long-term benefits, and significant
      improvement of quality of life when compared with best medical treatment. These
      benefits have to be weighed against potential surgery-related adverse events,
      device-related complications, and stimulus-induced side effects. The mean disease
      duration before initiating DBS in PD is currently about 13 years. It is presently
      investigated whether the optimal timing for implantation may be at an earlier
      disease-stage to prevent psychosocial decline and to maintain quality of life for
      a longer period of time.

PMID- 21180628
TI  - Improving symptom control in early Parkinson's disease.
AB  - Motor symptoms in Parkinson's disease (PD) are caused by a severe loss of
      pigmented dopamine-producing nigro-striatal neurons. Symptomatic therapies
      provide benefit for motor features by restoring dopamine receptor stimulation.
      Studies have demonstrated that delaying the introduction of dopaminergic medical
      therapy is associated with a rapid decline in quality of life. Nonmotor symptoms,
      such as depression, are common in early PD and also affect quality of life.
      Therefore, dopaminergic therapy should typically be initiated at, or shortly
      following, diagnosis. Monamine oxidase-B inhibitors provide mild symptomatic
      benefit, have excellent side effect profiles, and may improve long-term outcomes,
      making them an important first-line treatment option. Dopamine agonists (DAs)
      provide moderate symptomatic benefit but are associated with more side effects
      than levodopa. However, they delay the development of motor complications by
      delaying the need for levodopa. Levodopa (LD) is the most efficacious medication,
      but its chronic use is associated with the development of motor complications
      that can be difficult to resolve. Younger patients are more likely to develop
      levodopa-induced motor complications and they are therefore often treated with a
      DA before levodopa is added. For older patients, levodopa provides good motor
      benefit with a relatively low-risk of motor complications. Using levodopa with a
      dopa-decarboxylase inhibitor lessens adverse effects, and further adding a
      catechol-O-methyl transferase inhibitor can improve symptom control.

PMID- 21180629
TI  - Benefit of repetitive intrathecal triamcinolone acetonide therapy in
      predominantly spinal multiple sclerosis: prediction by upper spinal cord atrophy.
AB  - Intrathecal injection of triamcinolone acetonide (TCA) has been shown to provide
      substantial benefit in a subset of progressive multiple sclerosis (MS) patients
      with predominant spinal symptoms. We examined whether atrophy of the upper spinal
      cord (USC) as measured by MRI can serve as a predictive marker for response to
      repetitive intrathecal TCA application. Repetitive administration of 40 mg TCA
      was performed in 31 chronic progressive MS patients up to six times within 3
      weeks. Expanded Disability Status Scale (EDSS) and maximum walking distance (WD)
      were assessed before and after the treatment cycle. Cervical 3D T1-weighted
      images were acquired on a 1.5T scanner at baseline. Mean cross-sectional area of
      the USC was determined using a semi-automated volumetry method. Results were
      compared with a group of 29 healthy controls to group patients into those with
      and without atrophy. Results show a negative correlation between the degree of
      USC atrophy and treatment benefit. A higher treatment benefit in patients with
      little USC atrophy but short initial maximum WD was observed. Absence of USC
      atrophy as measured on MRI is a predictive marker for intrathecal TCA therapy
      outcome in progressive MS. Patients with initial poor walking abilities, but only
      little or no atrophy, benefited most from TCA therapy.

PMID- 21180630
TI  - Cyclophosphamide in multiple sclerosis: scientific rationale, history and novel
      treatment paradigms.
AB  - For patients with relapsing-remitting multiple sclerosis (RRMS), there are
      currently six approved medications that have been shown to alter the natural
      course of the disease. The approved medications include three beta interferon
      formulations, glatiramer acetate, natalizumab and mitoxantrone. Treating
      aggressive forms of RRMS and progressive disease forms of MS still presents a
      great challenge to neurologists. Intense immunosuppression has long been thought
      to be the only feasible therapeutic option. In patients with progressive forms of
      MS, lymphoid tissues have been detected in the central nervous system (CNS) that
      may play a critical role in perpetuating local inflammation. Agents that are
      currently approved for patients with MS have no or very limited bioavailability
      in the brain and spinal cord. In contrast, cyclophosphamide (CYC), an alkylating
      agent, penetrates the blood-brain barrier and CNS parenchyma well. However, while
      CYC has been used in clinical trials and off-label in clinical practice in
      patients with MS for over three decades, data on its efficacy in very
      heterogeneous groups of study patients have been conflicting. New myeloablative
      treatment paradigms with CYC may provide a therapeutic option in patients that do
      not respond to other agents. In this article we review the scientific rationale
      that led to the initial clinical trials with CYC. We will also outline the
      safety, tolerability and efficacy of CYC and provide neurologists with guidelines
      for its use in patients with MS and other inflammatory disorders of the CNS,
      including neuromyelitis optica (NMO). Finally, an outlook into relatively novel
      treatment approaches is provided.

PMID- 21180632
TI  - A one-year prospective, randomized, placebo-controlled, quadruple-blinded, phase
      II safety pilot trial of combination therapy with interferon beta-1a and
      mycophenolate mofetil in early relapsing-remitting multiple sclerosis (TIME MS).
AB  - BACKGROUND: Mycophenolate mofetil (MMF) is an oral DNA base synthesis inhibitor
      with immunomodulatory effects on B cells, T cells, and macrophages. OBJECTIVE: To
      conduct a safety and tolerability pilot study of interferon beta-1a (IFN-b1a) in
      combination with either placebo or oral MMF in multiple sclerosis (MS). METHODS:
      Twenty-four treatment-naive R-RMS patients participated in a one-year
      prospective, placebo-controlled, blinded, safety pilot clinical trial. Every
      patient injected weekly intramuscular interferon beta-1a. The cohort was then
      randomized (1 : 1) to either active oral MMF or identical-appearing placebo
      tablets. Clinical evaluations were assessed every 3 months, along with brain MRI
      scans performed at baseline and repeated every 60 days for one year.
      Comprehensive laboratory assessments were monitored for safety, along with
      adverse events. RESULTS: In this small pilot investigation, no differences were
      identified between the two treatment groups with respect to patient-reported
      adverse events, MRI metrics, or laboratory abnormalities. Notwithstanding these
      observations, and the limited number of patients treated, trends appeared to
      favor the combination therapy regimen. CONCLUSIONS: The combination treatment
      regimen of interferon beta-1a and MMF appeared to be well tolerated in this pilot
      study. Despite the small sample size, therapeutic trends were observed in favor
      of combination therapy. An adequately powered controlled trial of MMF in MS
      appears warranted.

PMID- 21180633
TI  - A randomized, blinded, parallel-group, pilot trial of mycophenolate mofetil
      (CellCept) compared with interferon beta-1a (Avonex) in patients with relapsing
      remitting multiple sclerosis.
AB  - BACKGROUND: Mycophenolate mofetil (MMF, CellCept(r)) has been utilized as an
      antirejection agent in transplant recipients and in patients with myriad
      autoimmune disorders including multiple sclerosis (MS). OBJECTIVE: To investigate
      radiographic and clinical safety involving monotherapy use of daily oral MMF (1 g
      b.i.d.) versus weekly intramuscular interferon beta 1a (Avonex(r) at 30 mcg) in
      relapsing-remitting MS (RRMS). METHODS: We organized a randomized, serial, 6
      monthly, MRI-blinded, parallel-group multicenter pilot study to determine the
      safety of MMF versus interferon beta monotherapy in 35 untreated patients with
      RRMS, all of whom exhibited evidence of gadolinium (Gd) enhancement on a
      screening MRI of the brain. The primary outcome was the reduction in the
      cumulative mean number of combined active lesions (CAL), new Gd-enhancing
      lesions, and new T2 lesions on MRI analyses. RESULTS: Both interferon beta and
      MMF appeared safe and well tolerated in the majority of patients. There was no
      difference between MMF therapy and the standard regimen of interferon beta
      therapy on the primary safety MRI endpoints of the study. However, the MMF group
      showed a trend toward a lower accumulation of combined active lesions, CAL, Gd
      and T2 lesions when compared with interferon beta treated patients. CONCLUSIONS:
      The results from this pilot study suggest that the application of MMF monotherapy
      in MS deserves further exploration.

PMID- 21180634
TI  - Diagnosis and treatment of cerebral vasculitis.
AB  - Vasculitides are characterized by inflammation and necrosis of the blood vessel
      wall. Large vessels including the aorta are affected in giant-cell arteritis,
      medium-size arteries in classic polyarteritis nodosa. The small-vessel
      vasculitides are separated in those with antineutrophil cytoplasm antibodies
      (ANCA) and those without. The primary angiitis of the central nervous system
      (PACNS) is a rare disorder affecting both medium- and small-sized vessels. Major
      symptoms of cerebral vasculitis are stroke, headache and encephalopathy.
      Diagnosis is based on laboratory and imaging findings. When cerebral affection
      occurs in systemic vasculitis an acute inflammatory response with raised
      erythrocyte sedimentation rate and increased values of C-reactive protein is
      present. In many cerebral vasculitides including PACNS, CSF studies reveal
      inflammatory findings. Magnetic resonance imaging, including ADC maps, diffusion
      and gradient echo sequences, is the investigation of choice to detect and monitor
      cerebral involvement. Certain MRI techniques and 18-fluorodeoxyglucose positron
      emission tomography allow the visualization of vessel wall inflammation when the
      lumen is still unaffected on angiography. The treatment recommendations for
      cerebral angitis are derived from protocols for systemic vasculitides. In
      general, a combination of steroids and pulse cyclophosphamide (CYC) is
      recommended for induction treatment. An alternative option is the use of the anti
      CD20 antibody rituximab. Methotrexate, azathioprine and mycophenolate mofetil
      are recommended as alternatives to CYC once remission is achieved.

PMID- 21180635
TI  - Progress in the management of paraneoplastic neurological disorders.
AB  - Paraneoplastic neurological disorders (PNDs) are a rare and diverse group of
      neurological conditions that can involve any part of the nervous system.
      Diagnosis is facilitated by finding well-recognized autoantibodies directed
      against neural antigens in the sera and the cerebrospinal fluid. Identifying and
      eliminating the underlying malignancy is the mainstay of treatment.
      Immunomodulatory treatment is gaining more acceptance especially, where a
      malignancy could not be identified, oncology treatment is completed, or along
      with cancer treatment. Literature review shows only a handful of systematic
      prospective case series. Multicenter, prospective controlled clinical trials are
      needed for future therapeutic advances.

PMID- 21180637
TI  - Discordant findings in color-coded duplex-sonography and magnetic resonance
      angiography in symptomatic internal carotid artery stenosis: implications for
      diagnostic work-up and early intervention.
AB  - BACKGROUND: Magnetic resonance angiography (MRA) is supposed to be the new 'gold
      standard' in the diagnosis of atherosclerotic disease of the extracranial
      arteries. METHODS: A case report is presented on a patient in whom discordant
      findings of the status of the left internal carotid artery (ICA) were identified
      in color-coded duplex-sonography and MRA. RESULTS: Left ICA stenosis was
      suspected in duplex-sonography, yet not confirmed in contrast-enhanced (CE) MRA
      reconstruction. Diagnosis was confirmed after surgery and in subsequent analysis
      of the original CE-MRI data. CONCLUSIONS: The analysis of source images must not
      be missed in MRA examinations. Conventional duplex-sonography may be superior in
      the estimation of the embolic potential of vascular lesions. Advanced CE
      techniques may therefore be adequate tools in differentiating patients eligible
      for carotid endarterectomy (CEA) or carotid stenting, avoiding the risk of peri
      interventional iatrogenic complications. It should urgently be further improved
      and validated.

PMID- 21180638
TI  - Do amyloid-lowering strategies work clinically?

PMID- 21180636
TI  - Treatment of dysautonomia in extrapyramidal disorders.
AB  - Although extrapyramidal diseases are commonly thought to solely affect the
      extrapyramidal motor system, nonmotor symptoms such as behavioural abnormalities,
      dysautonomia, sleep disturbances and sensory dysfunctions are also frequently
      observed. Autonomic dysfunction as an important clinical component of
      extrapyramidal disease (idiopathic Parkinson's disease, multiple system atrophy,
      progressive supranuclear palsy, dementia with Lewy bodies) is often not formally
      assessed and thus frequently misdiagnosed. Symptoms of autonomic dysfunction in
      general impact more on quality of life than motor symptoms. Appropriate symptom
      oriented diagnosis and symptomatic treatment as part of an interdisciplinary
      approach can greatly benefit the patient. Unfortunately, double-blind,
      randomized, controlled studies are scarce with the consequence that most
      recommendations are not based on the highest level of evidence. This review
      elaborates a limited overview on the treatment of cardiovascular,
      gastrointestinal, urogenital and sudomotor autonomic dysfunction in various
      extrapyramidal syndromes.

PMID- 21180639
TI  - Immunomodulation and postpartum relapses in patients with multiple sclerosis.
AB  - Multiple sclerosis (MS) mainly affects young women during a life period with
      desire for children. Relapse rate decreases during pregnancy and rises after
      delivery. Therefore, studies on satisfactory postpartum relapse prevention and
      its efficacy are essential. Previous smaller and uncontrolled studies suggested
      that intravenous immunoglobulin (IVIG) administration reduced the relapse rate
      following delivery. The objective of our observational study was to compare the
      efficacy of IVIG application, treatment with other immunomodulatory compounds or
      no treatment at all on the postpartal relapse rate in female MS patients from our
      pregnancy database. One hundred and twenty four pregnancies were followed in a
      partly prospective design. Relapse rate was reduced during pregnancy (p50.001)
      and increased during the initial 3 months after delivery in all MS patients
      (p50.001). The relapse rate reduction showed only a trend in favour of the IVIG
      treated women, probably due to the small number of patients. However, analysing
      the expected number of relapses, IVIG treated patients had significantly less
      relapses postpartum than the untreated control group matched for disease activity
      before and during pregnancy (chi(2), p= 0.013). The results suggest that IVIG
      could be an option to prevent postpartum relapse of MS.

PMID- 21180641
TI  - Cellular repair strategies in Parkinson's disease.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder
      after Alzheimer's disease, affecting 0.7% of the elderly population (defined as
      over 65 years of age). PD is clinically characterized by resting tremor, muscular
      rigidity, hypokinesia and postural instability. These motor symptoms result
      largely from the deficiency or dysfunction of dopaminergic neurons in the
      substantia nigra. Histopathological analysis reveals depletion of dopaminergic
      neurons as well as eosinophilic intracytoplasmic inclusions (Lewy bodies) in
      surviving neurons of the substantia nigra and other brain regions. The molecular
      pathogenesis is linked to protein misfolding by compromised alpha-synuclein
      and/or related proteins (synucleinopathy). Therefore, successful therapy of motor
      symptoms aims for the restoration of dopaminergic neurotransmission.
      Pharmacological drug treatment is usually effective only at an early stage of the
      disease but cannot halt progressive neuronal degeneration. With recent
      developments in stem cell technology, cell repair or replacement approaches came
      into focus. Here, we review new therapeutic strategies resulting from the innate
      propensity of the adult brain to generate new neurons, either by pharmacological
      stimulation of endogenous adult stem cell population or exogenous cell
      transplantation modalities.

PMID- 21180640
TI  - Psychopathology in multiple sclerosis: diagnosis, prevalence and treatment.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous
      system. Demyelinization of nerve fibres not only affects the motor and sensory
      systems functionally, but may also cause psychopathological signs and symptoms.
      In addition to the psychiatric manifestations of MS, many patients have reactive
      psychological problems that are often hard to distinguish from the 'organic'
      causation of psychopathology. In any event, psychiatric comorbidity in MS
      deserves greater clinical attention than has been previously paid, because the
      presence of psychopathology may have deleterious effects on the disease process
      and impair coping with disability.

PMID- 21180642
TI  - Subcutaneous Interferon Beta-1a Has a Positive Effect on Cognitive Performance in
      Mildly Disabled Patients with Relapsing-Remitting Multiple Sclerosis: 2-Year
      Results from the COGIMUS Study.
AB  - The effect of interferon (IFN) beta-1a (44 and 22 MUg subcutaneously [sc] three
      times weekly [tiw]) on cognition in mildly disabled patients with relapsing
      remitting multiple sclerosis (McDonald criteria; Expanded Disability Status Scale
      =4.0) was assessed by validated neuropsychological testing at baseline and at
      regular intervals for up to 2 years in this ongoing open-label, 3-year study.
      Year-2 data were available for 356 patients (22 MUg, n = 175; 44MUg, n = 181).
      The proportion of patients with impaired cognitive function was stable during the
      study: 21.4% at baseline and 21.6% at 2 years. At 2 years, the proportion of
      patients with =3 impaired cognitive tests was significantly lower in the 44 MUg
      treatment group (17.0%) compared with the 22 MUg group (26.5%; p = 0.034),
      although there was already a trend towards a higher proportion of patients with
      cognitive impairment in the 22 MUg group at baseline. Factors associated with
      impairment in = three cognitive tests after 2 years were age (odds ratio [OR]:
      1.05; 95% confidence interval [CI]: 1.00-1.09), verbal intelligence quotient (OR:
      0.95; 95% CI: 0.92-0.98), and having = three impaired cognitive tests at baseline
      (OR: 11.60; 95% CI: 5.94-22.64). These interim results show that IFN beta-1a sc
      tiw may have beneficial effects on cognitive function as early as 2 years after
      treatment initiation, but the final 3-year data of the study are required to
      confirm these results.

PMID- 21180643
TI  - New treatment options in status epilepticus: a critical review on intravenous
      levetiracetam.
AB  - The effectiveness of Levetiracetam (LEV) in the treatment of focal and
      generalised epilepsies is well established. LEV has a wide spectrum of action,
      good tolerability and a favourable pharmacokinetic profile. An injectable
      formulation has been released as an intravenous (IV) infusion in 2006 for
      patients with epilepsy when oral administration is temporarily not feasible.
      Bioequivalence to the oral preparation has been demonstrated with good
      tolerability and safety enabling a smooth transition from oral to parenteral
      formulation and vice versa. Although IV LEV is not licensed for treatment of
      status epilepticus (SE), open-label experience in retrospective case series is
      accumulating. Until now (August 2008) 156 patients who were treated with IV LEV
      for various forms of SE have been reported with an overall success rate of 65.4%.
      The most often used initial dose was 2000-3000 mg over 15 minutes. Adverse events
      were reported in 7.1%, and were mild and transient. Although IV LEV is an
      interesting alternative for the treatment of SE due to the lack of centrally
      depressive effects and low potential of drug interactions, one has to be aware of
      the nonrandomised retrospective study design, the heterogenous patient population
      and treatment protocols, and the publication bias inherent in these type of
      studies. Only a large randomised controlled trial with an adequate comparator
      will reveal the efficacy and effectiveness of this promising new IV formulation.

PMID- 21180644
TI  - Primary CNS lymphoma.
AB  - Primary CNS Lymphoma (PCNSL) accounts for 3% of all primary brain tumors with a
      median age at onset of about 62 years. In the vast majority of cases, PCNSL
      presents as unifocal or multifocal enhancing lesions on MRI, frequently adjacent
      to the ventricles. Stereotactic biopsy is the diagnostic procedure of choice
      revealing high-grade malignant non-Hodgkin's B-cell lymphoma in more than 90% of
      cases. Therapy is not evidence based. When eligible, patients should be included
      in clinical trials. In patients younger than 60 years cure is the aim.
      Polychemotherapy based on high-dose methotrexate (MTX) or alternatively high-dose
      chemotherapy with autologous stem cell rescue should be offered to patients
      eligible for this regimens. For patients over 60 years of age no curative regimen
      with acceptable toxicity has yet been established. An MTX-based chemotherapy, for
      example, in combination with temozolomide, is recommended. The role of
      radiotherapy as part of the initial treatment is not established; however, the
      combination of radiotherapy with MTX-based chemotherapy potentially leads to
      severe long-term neurotoxic sequelae. Therefore, radiotherapy as part of the
      initial therapy is not recommended by the author outside clinical trials. At
      relapse or in cases of refractory disease, patients will frequently benefit of
      salvage therapy, which depends on the initial treatment.

PMID- 21180645
TI  - Therapeutic options for continuous dopaminergic stimulation in Parkinson's
      disease.
AB  - Treatment of Parkinson's disease aims to replace dopaminergic transmission at
      striatal synapses. In the normal state, nigral neurons fire continuously,
      exposing striatal dopamine receptors to relatively constant levels of dopamine.
      In the disease state, periodic dosing and the short half-life of antiparkinsonian
      drugs leads to more intermittent stimulation. Abnormal pulsatile stimulation of
      striatal dopamine receptors may lead to dysregulation of genes and proteins in
      downstream neurons and consequently, alterations in neuronal firing patterns.
      This may ultimately lead to motor complications. In order to prevent the
      development of motor complications a therapy that provides continuous
      dopaminergic stimulation as observed in the normal state would be ideal.
      Different routes of administration of levodopa and other dopaminergic drugs have
      been tried to achieve continuous dopaminergic stimulation (CDS). This review
      discusses the various methods available to achieve this goal with particular
      emphasis on duodenal dopa administration.

PMID- 21180647
TI  - The significance of GlgE as a new target for tuberculosis.
AB  - Largely neglected by the industrialized world for decades, tuberculosis (TB),
      caused by the bacterium Mycobacterium tuberculosis, has made a fulminant return
      to the public health agenda as a major global health threat. The worsening of the
      TB pandemic is driven by the rapid emergence of multidrug-resistant and
      extensively drug-resistant M. tuberculosis strains, which are virtually
      untreatable with current chemotherapies. The search for new strategies to combat
      such resistant strains is of paramount importance for control of the TB pandemic.
      In searching for new vulnerable processes in M. tuberculosis to enable the
      rational design of more efficient anti-TB chemotherapy, a novel class of
      antimycobacterial drug targets has recently been discovered; it is represented by
      GlgE, an essential maltosyltransferase that elongates linear alpha-glucans as
      part of a synthetic lethal biosynthetic pathway. Inactivation of GlgE causes
      accumulation of a toxic phosphosugar intermediate, maltose 1-phosphate, which
      drives the bacilli into a suicidal self-poisoning cycle that elicits a complex
      stress profile, eventually resulting in DNA damage and death of M. tuberculosis.
      GlgE combines many favorable properties that make it a highly attractive novel
      drug target for chemotherapy of TB.

PMID- 21180646
TI  - Natalizumab in the treatment of multiple sclerosis.
AB  - Natalizumab reduced the rate of clinical relapse at one year by 68% and the risk
      of sustained progression of disability by 42-54% over 2 years in its pivotal
      phase III trial (AFFIRM) in relapsing-remitting multiple sclerosis (RRMS).
      Natalizumab is generally well tolerated, but due to rare and potentially fatal
      side-effects, it was approved with a restricted-distribution format in 2006.
      Expert statements and the European Medical Agency recommend the use of
      natalizumab after failure of first-line disease-modifying therapies in patients
      with relapsing forms of MS. As part of the risk management plan, worldwide
      extensive safety programmes aim to provide more data on natalizumab safety in
      clinical practice. At the end of September 2008, 48 000 patients have received
      natalizumab and 18000 patients are on treatment for at least 1 year. The
      assessment of risk and benefit is still ongoing.

PMID- 21180649
TI  - Trioxaquines: hybrid molecules for the treatment of malaria.
AB  - Artemisinin, with its 1,2,4-trioxane as active motif, is now the first-line
      treatment for multidrug-resistant malaria. The endoperoxide ring is essential for
      the antimalarial activity of artemisinin. Based on its mechanism of action, new
      hybrid molecules named trioxaquines with a dual mode of action have been
      designed. Trioxaquines are made by the covalent attachment of a trioxane, having
      alkylating ability, to a quinoline, known to easily penetrate within infected
      erythrocytes. This review discusses the importance of various hybrid molecules of
      artemisinin and 4-aminoquinoline in the treatment of malaria and the evolution of
      a trioxaquine hybrid as a promising antimalarial drug candidate.

PMID- 21180648
TI  - Inhibition of potassium currents as a pharmacologic target for investigation in
      chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) represents 22-30% of all leukemia cases, thus
      being the most commonly diagnosed form of adult leukemia in the Western world. On
      a cellular level, the disease progresses due to the prolonged survival of B-cell
      CLL cells arrested in the G0 stage of the cell cycle. The current standard
      treatment for CLL is a combination regimen containing purine analogues and
      monoclonal antibodies. Although response rates to such regimens in previously
      untreated patients are high, patients with CLL invariably experience relapse and
      often acquire high-risk chromosomal abnormalities. Therefore, the search for
      novel avenues in CLL treatment is warranted. In this manuscript, we will describe
      theoretical premises and some preliminary data making the case for inhibitors of
      the potassium currents as possible proapoptotic agents that warrant investigation
      as a potential pharmacologic target in CLL.

PMID- 21180650
TI  - Electroporation: a promising method for the nonviral delivery of DNA vaccines in
      humans?
AB  - The without a doubt major obstacle for making DNA vaccines a commercial success
      is delivery. If delivery cannot be made simple, cheap and effective, DNA vaccines
      may not become a viable option for human use. Numerous clinical trials have
      confirmed that a standard needle and syringe simply do not do the job, i.e.,
      delivering the DNA payload inside the cell. Having recognized this shortcoming,
      investigators have developed several new approaches for DNA vaccine delivery. In
      particular, new types of delivery devices, originally intended for in vitro use,
      have been applied for in vivo delivery. These include particle bombardment or
      biolistic delivery, and in vivo electroporation (EP). Importantly, both
      techniques seem to overcome the size barrier, meaning that they work in both mice
      and larger animals. In vivo EP has the key features of improved DNA uptake,
      increased antigen expression and a local inflammation. These factors are
      essential to make DNA vaccines effective in a larger host. Early data from
      clinical trials with DNA vaccines delivered by in vivo EP are cautiously
      promising. Thus, we may be entering a new era of DNA vaccination where we start
      to see clinical effects in humans; however, these may also be accompanied by side
      effects, as the vaccines become more effective.

PMID- 21180651
TI  - Epigenetic alterations of tumor marker microRNAs: towards new cancer therapies.
AB  - MicroRNAs (miRNAs) are a class of short noncoding RNAs that participate in
      mastering the balance of gene-regulating networks. By targeting and controlling
      expression of messenger RNA, miRNAs can control highly complex signal
      transduction pathways and other biological pathways. Unique aberrant expression
      of miRNA at each stage of cancer development suggests that miRNA could play a
      novel role in cancer diagnosis and therapeutic strategies. Accumulated
      information on epigenetic modification of miRNA suggests a promising platform for
      miRNA in cancer therapy. Clinical applications exploiting the understanding of
      miRNA's function will be the next great challenge in cancer research.

PMID- 21180652
TI  - Molecule of the Month. TAK-875.

PMID- 21180653
TI  - Are we living in the end of the blockbuster drug era?
AB  - For the last two decades, we have seen remarkable growth in the pharmaceutical
      industry. This growth has mainly been due to the approximately 100 new
      blockbuster drugs, such as Lipitor(r) (atorvastatin) and Plavix(r) (clopidogrel).
      More than half of the revenue of major pharmaceutical companies and above one
      third of the total pharmaceutical revenues came from the sales of these
      blockbuster drugs. Questions concerning the fate of these blockbuster drugs are
      beginning to surface as they are approaching their patent expiration dates, and
      as they are expected to face significant competition from generic versions.
      Branded drugs with more than USD 120 billion in sales (as of 2008) are expected
      to lose their patent protection in the next 3 to 4 years, while the less
      expensive generic versions are ready to enter the market. It is plausible that a
      major paradigm shift in our thinking is needed to stay innovative, competitive
      and economically feasible in this new era of drug development. A new wave of
      innovations is expected to boost the blockbuster regime. Herein, we discuss the
      different threats facing the branded monopoly, as well as some of the hopeful
      expectations for the blockbuster drug.

PMID- 21180654
TI  - Primary psychiatric prevention in children and adolescents.
AB  - BACKGROUND: Approximately 21% of US children age 9 to 17 have a diagnosable
      mental illness with some degree of impairment. As early-onset mental illness may
      persist throughout the life span, effective primary mental health prevention
      programs are of paramount importance. METHODS: We conducted a literature review
      of various preventive programs targeting childhood-onset psychopathology. We
      attempted to select those programs that present the strongest data on efficacy
      and those that are most commonly cited. RESULTS: Modifiable and nonmodifiable
      risk factors and different primary prevention strategies with positive outcomes
      have been identified for anxiety disorders, eating disorders, substance abuse,
      disruptive behavior disorders, and suicide in children. The reported results for
      attention-deficit/hyperactivity disorder (ADHD) and early-onset schizophrenia are
      neither uniform nor encouraging. CONCLUSIONS: Based on our review, there is ample
      evidence to conclude that primary preventive intervention has the potential to be
      effective for some mental health disorders, promoting positive development,
      particularly in children of all ages in high-risk environments. Additional
      research is needed to further investigate the validity and reliability of various
      preventive strategies.

PMID- 21180655
TI  - Primary prevention in psychiatry--adult populations.
AB  - BACKGROUND: The concept of prevention in psychiatry is unique. It includes
      promotion of mental health, identification of risk factors across the life cycle,
      and appropriate early interventions. Recent emphasis on intervention early in the
      development of mental illness has resulted in several preventive programs with
      varying degrees of success. METHODS: We reviewed the literature on primary
      prevention in mental health, categorizing reports as evidence of universal,
      selective, or indicated prevention. RESULTS: Indicated prevention through early
      intervention is the best-researched area of prevention in the spectrum of
      psychotic disorders, especially schizophrenia. Pharmacotherapy for ultra high
      risk individuals combined with cognitive-behavioral therapy (CBT) has shown
      promising results in several studies. Strategies that teach younger individuals
      to cope with stress and provide psychosocial support have been effective in
      preventing mood and anxiety disorders. CONCLUSIONS: There is evidence that
      primary prevention may delay the onset of mental illness. Future research on the
      etiologies of mental illnesses is required to facilitate development of
      additional primary prevention strategies. These efforts may contribute to
      reallocation of resources and enactment of public policies that curb the
      staggering effects of mental illness on society.

PMID- 21180656
TI  - Primary prevention in geriatric psychiatry.
AB  - BACKGROUND: It is estimated that the number of older adults with mental illness
      will increase from 4 million in 1970 to 15 million by 2030. The cost of untreated
      mental illness in the United States is estimated to be >$100 billion annually and
      nearly half of that cost can be attributed to persons age >=60. In this paper we
      present a comprehensive review of empiric data available on primary prevention
      for the most common psychiatric illnesses in this patient population. METHODS: We
      did an English language literature review of published studies and selected only
      those with the strongest emphasis on primary prevention for the most common
      psychiatric illnesses in older adults. RESULTS: Modifiable and nonmodifiable risk
      factors and several primary prevention strategies have been described, several of
      them with positive outcomes mainly for depressive disorders and suicide. In
      conditions such as bipolar disorder, dementias, and geriatric schizophrenia,
      there is either a paucity of studies or no robust primary prevention strategies
      identified. CONCLUSIONS: Modification of risk factors, a healthy lifestyle that
      includes a healthy diet, exercise, socialization, and education are important
      aspects of primary prevention in elderly patients. Genetic engineering and
      vaccine therapies may open new and exciting opportunities for prevention of many
      psychiatric illnesses in the near future.

PMID- 21180657
TI  - Primary prevention of psychiatric illness in special populations.
AB  - BACKGROUND: Some populations appear to be particularly vulnerable to the
      development of psychiatric symptomatology related to life events and biologic or
      social/cultural factors. Such groups include individuals who have experienced
      traumatic events, military personnel, individuals with serious medical
      conditions, postpartum women, and immigrants. This study reviews the literature
      regarding primary prevention of psychiatric disorders in special populations and
      identifies a variety of universal, selective, and indicated prevention measures
      aimed at minimizing the psychiatric sequelae in these groups. METHODS: The
      authors reviewed the literature regarding the prevention of psychiatric symptoms
      in trauma/abuse victims, individuals in the military, oncology patients, patients
      with diabetes, pregnant/postpartum women, and immigrants. RESULTS: The literature
      on primary prevention of psychiatric illness in the special populations
      identified is rather limited. Universal prevention may be beneficial in some
      instances through public awareness campaigns and disaster planning. In other
      instances, more specific and intensive interventions for individuals at high risk
      of psychiatric illness may improve outcomes, for example, crisis counseling for
      those who have experienced severe trauma. CONCLUSIONS: Primary prevention of
      psychiatric illness may be an attainable goal via implementation of specific
      universal, selected, and indicated primary prevention measures in special
      populations.

PMID- 21180658
TI  - Effects of exogenous glucocorticoid on combat-related PTSD symptoms.
AB  - BACKGROUND: Very few systematic human studies focus on changing the underlying
      traumatic memory after posttraumatic stress disorder (PTSD) has been established.
      Evidence from animal and human studies indicates that cortisol can be used to
      address traumatic memories. This translational pilot study is based on our
      previous rodent research in which extinction of fear memories was enhanced by
      glucocorticoids. The current study aims to assess the effectiveness of
      glucocorticoids in augmenting memory extinction and reducing clinical symptoms in
      veterans with combat-related PTSD. METHODS: In a double-blind, placebo-controlled
      study, veterans with combat-related PTSD were exposed to a memory reactivation
      task using well established imagery and psychophysiology assessment technique
      followed by administration of either glucocorticoid or placebo. RESULTS: One week
      after glucocorticoid or placebo administration, participants who received the
      study medication showed significant PTSD-related symptom (cluster C) improvement
      compared with control participants who received placebo only. However, reduction
      of symptoms degraded at a 1-month postadministration assessment. CONCLUSIONS:
      These findings are consistent with a glucocorticoid-mediated enhancement of
      extinction to ameliorate PTSD symptoms. The use of traumatic memory reactivation
      temporally paired with glucocorticoid administration holds potential for
      developing a viable therapeutic option.

PMID- 21180659
TI  - Effect of omega-3 fatty acids on valproate plasma protein binding.

PMID- 21180660
TI  - Stuttering onset associated with streptococcal infection: a case suggesting
      stuttering as PANDAS.

PMID- 21180661
TI  - Differential diagnosis and therapeutic management of schizoaffective disorder.

PMID- 21180662
TI  - Transcranial magnetic stimulation for major depressive disorder: introduction.

PMID- 21180663
TI  - Transcranial magnetic stimulation for major depressive disorder: a pragmatic
      approach to implementing TMS in a clinical practice.
AB  - Another option for managing major depressive disorder (MDD) became available in
      October 2008 with the Food and Drug Administration's (FDA) market clearance of
      NeuroStar TMS (transcranial magnetic stimulation) Therapy System. A panel of
      psychiatrists who have been treating patients with NeuroStar TMS Therapy in their
      clinics assembled for a virtual roundtable discussion regarding their
      experiences. In this supplement, the panel addresses the following issues: the
      FDA-cleared indication for use of NeuroStar TMS Therapy; logistic and staffing
      considerations in the outpatient setting; selecting the right patient for TMS
      Therapy; talking with patients and family about TMS Therapy. To give the overview
      a meaningful context, each panelist shares a personal account of a patient case,
      describing the treatment course and outcomes achieved with TMS Therapy.

PMID- 21180664
TI  - Major depressive disorder and other medical illness: a two-way street.

PMID- 21180665
TI  - Switch or augment? Lessons from STAR*D.

PMID- 21180666
TI  - Switching, combination, and augmentation strategies for major depressive
      disorder.

PMID- 21180667
TI  - PRECEDE-PROCEED model modification in community-based oral health promotion by
      using the linear structural relations programme.
AB  - PURPOSE: The PRECEDE-PROCEED (P-P) model is a framework for designing health
      education/promotion programmes. While the P-P model has been used to design
      community-based oral health programmes, outcome assessments of the model are
      seldom reported. The aim of the present study was to explore whether pathways in
      the P-P model accurately reflect the current status of environmental/behavioural
      assessment in a Japanese community and to examine whether using the linear
      structural relations (LISREL) programme would improve the model. MATERIALS AND
      METHODS: In a community health centre in Japan, a questionnaire with 29 items
      regarding oral health was distributed to 824 mothers with 3-year-old children.
      The items were compiled into eight variables that were tested using the LISREL
      programme. Goodness-of-fit index (GFI), adjusted goodness-of-fit index (AGFI) and
      root mean square error of approximation (RMSEA) were statistically analysed
      before and after P-P model modification. RESULTS: The GFI, AGFI and RMSEA were
      0.913, 0.776 and 0.161 before, and 0.975, 0.939 and 0.075 after P-P model
      modification, respectively. Indirect effects on the quality of life from the
      predisposing, reinforcing and enabling factors became stronger than those in the
      initial P-P model. The overall fit of the modified P-P model was significantly
      better than that of the P-P model without modification, which did not accurately
      reflect the status of environmental/behavioural assessment in the community.
      CONCLUSIONS: The modified P-P model reflected the current status of
      environmental/behavioural assessment in the community. Health education models
      should be tested rigorously to ensure that they fit the reality of people's
      behaviour.

PMID- 21180668
TI  - Associations among sleep disturbance, vitality, fatigue and oral health.
AB  - PURPOSE: The objective of the present study was to explore the moderating effects
      of sleep disturbance, fatigue and vitality on self-reported oral-health status
      and oral-health related behaviours. MEASUREMENTS AND RESULTS: The present study
      sample consisted of 213 first-year dental students at the University of Medicine
      and Pharmacy 'Carol Davila', Bucharest, Romania. The questionnaire included
      information about sociodemographic factors, behavioural variables and self
      reported oral-health status. Subjective Vitality Scale, Fatigue Assessment Scale
      and Karolinska Sleep Questionnaire were used to assess quality of sleep, vitality
      and fatigue. The duration of sleep in 41.2% of students was < 7 h per night. It
      was revealed that 11.7% of the students experienced daily disturbed sleep, 20.4%
      had daily premature awakening and 50.5% presented frequent difficulties
      awakening. Significant differences were found among disturbed sleep, impaired
      awakening, vitality and fatigue scales according to several variables: perceived
      dental health, satisfaction by appearance of own teeth, self-reported gingival
      condition, mouth rinse frequency and reason for the dental visit, while multiple
      linear regression analyses revealed that vitality and impaired awakening were
      independent determinants of self-rated oral and gingival health status. Disturbed
      sleep index, impaired awakening, fatigue and vitality were positively associated
      with oral-health related behaviours. CONCLUSIONS: The authors concluded that the
      disturbed sleep index, impaired awakening, fatigue and vitality were associated
      with oral-health status and behaviour.

PMID- 21180669
TI  - Prevalence and distribution of tooth wear among Sri Lankan adolescents.
AB  - PURPOSE: The aim of the present study was to assess the prevalence, distribution
      and sociodemographic factors associated with tooth wear among Sri Lankan
      adolescents. MATERIALS AND METHODS: A total of 1200 17-year-olds were selected
      from government, private and international schools in the Colombo district of Sri
      Lanka using a two-stage cluster sampling technique. The data were collected using
      a pretested, validated self-administered questionnaire and by conducting a
      clinical examination. Tooth wear was recorded using a modified version of Smith
      and Knight's tooth wear index. RESULTS: The prevalence of tooth wear among Sri
      Lankan adolescents was found to be 22.4%. In nearly 13.7%, tooth wear was
      confined to the enamel, whereas 8.7% had wear lesions extending up to the
      dentine. Occlusal surface was the most frequently affected surface, while the
      first molar was the most frequently affected tooth. Tooth wear was significantly
      associated with the type of school attended, father's occupational status and
      mother's level of education. CONCLUSIONS: The present study found that nearly one
      fourth of the adolescents were affected by tooth wear. These findings are in
      agreement with those from developed countries where tooth wear has been shown to
      be an emerging oral health problem.

PMID- 21180670
TI  - Prevalence of malocclusion and index of orthodontic treatment need in children in
      Tehran.
AB  - PURPOSE: The aim of the present study was to determine the prevalence of
      malocclusion among schoolgirls and to assess malocclusion using the Index of
      Orthodontic Treatment Need (IOTN). MATERIALS AND METHODS: A total of 350 subjects
      were selected by a multistage randomised cluster sampling method. All of the
      selected subjects were schoolgirls aged 14 to 17 years. Malocclusion was
      determined using the IOTN. A chi-square test was performed to evaluate the data
      obtained. RESULTS: The present study reported that 16.3% of subjects had no
      treatment need, 35.7% had a mild treatment need, 35.4% had a moderate treatment
      need and a further 5.2% to 7.4% had a severe to extreme treatment need,
      respectively. Therefore, the prevalence of malocclusion was found to be 83.7%
      among Tehranian schoolgirls of age 14 to 17 years. CONCLUSIONS: The prevalence of
      malocclusion is very high among Tehranian schoolgirls; therefore, greater care is
      required to reduce this prevalence.

PMID- 21180671
TI  - Prevalence of allergy to latex gloves among dental professionals in Udaipur,
      Rajasthan, India.
AB  - PURPOSE: Nowadays, gloves are worn routinely by most general dental practitioners
      while treating patients, with latex being the most commonly used glove material
      worldwide. The aim of the present study was to determine the prevalence of
      allergy to latex gloves among dental professionals of Udaipur, Rajasthan, India.
      MATERIALS AND METHODS: In this cross-sectional study, a total of 163 dental
      professionals (73% males and 27% females) were surveyed using a pre-tested self
      administered questionnaire. The questionnaire was comprised of a total of 12
      items and gave information about the participants and their glove use, namely
      demographic profile, working habits and glove use, signs and symptoms related to
      glove use, any other type of allergy, as well as precautions taken to minimise
      it. The statistical analysis was performed using chi-square and Fisher's exact
      tests to compare frequency and percentage. The level of significance was set at P
      u 0.05. RESULTS: A total of 26 (16%) dental professionals reported allergy to
      latex gloves, of which females (27.3%) reported significantly greater allergy
      than males (11.8%) (P = 0.016). The number of years of glove use was
      significantly associated with allergy to latex gloves (P = 0.000). The prevalence
      of allergy to latex gloves was significantly greater for those who had allergy to
      pollen grains, foodstuffs and rubber dam, those who had asthma or history of
      eczema and those with family history of allergy. However, allergy to latex gloves
      was independent of age, type of gloves used, hours of use per day as well as
      number of patients seen per day. CONCLUSIONS: The present study showed a high
      rate of allergy to latex gloves among dental professionals in Udaipur, Rajasthan,
      India.

PMID- 21180673
TI  - Assessment of caries experience in 12-year-old adolescents in Piracicaba, Sao
      Paulo, Brazil.
AB  - PURPOSE: The aim of the present study was to analyse the association between
      socioeconomic and behavioural factors and the presence of active non-cavitated
      caries lesions in 12-year-old adolescents in Piracicaba, Sao Paulo, Brazil.
      MATERIALS AND METHODS: A cross-sectional study was carried out in 1001, 12-year
      old adolescents who were selected by the cluster sampling method. A modified
      version of the World Health Organization criteria for identifying lesions
      including white lesions (WL) in enamel was used. Information on behavioural and
      socioeconomic factors was obtained using a semi-structured questionnaire. The
      outcome variables were DMFS, DMFS+WL and WL. The data obtained were analysed
      using the chi-square test and a logistic regression model. RESULTS: The mean DMFS
      was 1.87 (SD = 3.05) and DMFS+WL was 2.27 (SD = 3.66). The logistic regression
      model showed that income was statistically significantly associated with DMFS,
      DMFS+WL and WL, whereas educational level of the father, number of residents in
      the house and number of dental visits were associated with DMFS and DMFS+WL. The
      onset of toothbrushing was associated with WL. CONCLUSIONS: The present study
      showed that economic factors are associated with all stages of caries
      development. In addition to these factors, family size, number of dental visits,
      educational level of the father and onset of toothbrushing could be considered
      markers of dental health risk.

PMID- 21180674
TI  - Comparative evaluation of garlic extract mouthwash and chlorhexidine mouthwash on
      salivary Streptococcus mutans count - an in vitro study.
AB  - PURPOSE: The aim of the present study was to assess and compare the antibacterial
      effect of garlic extract with those of chlorhexidine and negative control
      mouthwashes against Streptococcus mutans. MATERIALS AND METHODS: The present
      study was carried out in two phases. In Phase 1, the zone of inhibition of
      various concentrations of garlic extract against S. mutans was determined using
      the cup and plate method. The minimum concentration at which a zone of inhibition
      appeared was further employed to prepare a mouthwash that was used in Phase 2.
      This phase included 45 dental students whose baseline salivary S. mutans level
      was assessed. They were randomly divided into three groups: '1' representing
      students using garlic extract mouthwash (garlic extract + water + sorbitol +
      spearmint oil), '2' representing those using chlorhexidine (0.2%) mouthwash and
      '3' representing those using a negative control (water + sorbitol + spearmint
      oil). All of the subjects were advised to use 10 ml of the assigned mouthwash
      once daily after their last meal for a duration of 7 days. On day 8, the post
      treatment salivary S. mutans counts were assessed, and the data were analysed and
      compared by performing appropriate statistical tests. RESULTS: Phase 1: the 3%
      concentration was the minimum concentration at which a zone of inhibition was
      observed. Phase 2: a reduction in post-test S. mutans counts in all three groups
      was found. The mean difference that was observed in the garlic extract group was
      5.23 x 105 CFU/ml, in the chlorhexidine group 2.63 x 105 CFU/ml and in the
      negative control group 1.18 x 105 CFU/ml. The differences among all three groups
      were statistically significant (P < 0.05) and that between the negative control
      and the garlic group was highly significant (P < 0.001). CONCLUSIONS: Garlic
      extract is effective against S. mutans when tested both in vitro and in vivo. As
      S. mutans is one of the primary aetiological organisms in dental caries
      development (Loesche, 1986), and in the present study garlic extract has been
      shown to be effective against S. mutans, garlic extract mouth rinse might be used
      as an effective remedy in the prevention of dental caries.

PMID- 21180675
TI  - Evaluating an experimental dentifrice containing chloramine-T: a preliminary
      study.
AB  - PURPOSE: The aim of the present study was to evaluate the clinical efficacy of an
      experimental dentifrice (CH) containing an antimicrobial agent (1% chloramine-T).
      MATERIALS AND METHODS: A clinical, fully randomised, double-blind comparative
      study was designed for 30 selected patients aged 15 to 50 years, with no
      periodontal disease, decay or other oral diseases, good general health and the
      presence of dental plaque and sulcus bleeding. Baseline Turesky modified plaque
      index (PI) and sulcus bleeding index (SBI) were scored for all patients.
      Volunteers randomly received the experimental dentifrice (CH) or a commercial
      brand dentifrice containing triclosan (TR). Both dentifrices were provided in
      identical, number-labelled tubes, and the subjects were instructed to use the
      supplied dentifrice only for their usual oral hygiene, three times a day for a
      duration of 7 days. After 7-day use of dentifrices, the PI and SBI were assessed
      again. The data obtained were subjected to the Kruskal- Wallis test, followed by
      Dunn's post hoc test. RESULTS: After 7-day use of dentifrices, the PI scores
      diminished significantly for both evaluated dentifrices. The SBI values decreased
      significantly for both experimental and commercial-brand dentifrices.
      CONCLUSIONS: Both dentifrices reduced PI and SBI. By comparing the experimental
      and gold-standard dentifrice, it was found that there was no statistically
      significant difference between the PI and SBI scores after their use, suggesting
      that they exerted a similar effect on the oral health indexes.

PMID- 21180672
TI  - Use of caries-preventive agents in children: findings from the dental practice
      based research network.
AB  - PURPOSE: Scientific evidence supports the application of caries-preventive agents
      in children and adolescents, and this knowledge must be applied to the practice
      of dentistry. There are few multi-region data that allow for comparisons of
      practice patterns between types of dental practices and geographical regions. The
      objective of the present study was to characterise the use of specific caries
      preventive agents for paediatric patients in a large multi-region sample of
      practising clinicians. METHODS: The present study surveyed clinicians from the
      Dental Practice-based Research Network who perform restorative dentistry in their
      practices. The survey consisted of a questionnaire that presented a range of
      questions about caries risk assessment and the use of preventive techniques in
      children aged 6 to 18 years. RESULTS: Dental sealants (69%) or in-office fluoride
      (82%) were the most commonly used caries-preventive agents of the caries
      preventive regimens. The recommendation of at-home caries-preventive agents
      ranged from 36% to 7%,with the most commonly used agent being non-prescription
      fluoride rinse. Clinicians who practised in a large group practice model and
      clinicians who come from the Scandinavian region use caries risk assessment more
      frequently compared to clinicians who come from regions that had, predominantly,
      clinicians in private practice. Whether or not clinicians used caries risk
      assessment with their paediatric patients was poorly correlated with the
      likelihood of actually using caries-preventive treatments on patients.
      CONCLUSIONS: Although clinicians reported the use of some form of in-office
      caries-preventive agent, there was considerable variability across practices.
      These differences could represent a lack of consensus across practising
      clinicians about the benefits of caries-preventive agents, or a function of
      differing financial incentives, or patient pools with differing levels of overall
      caries risk.

PMID- 21180676
TI  - Microbiological profiles in saliva and supragingival plaque from caries-active
      adolescents before and after a short-term daily intake of milk supplemented with
      probiotic bacteria - a pilot study.
AB  - PURPOSE: The aim of the present pilot study was to investigate the microbial
      profile in saliva and supragingival plaque samples collected from caries-active
      adolescents before and after a daily short-term intake of milk supplemented with
      the probiotic bacteria. MATERIALS AND METHODS: The present study group consisted
      of 18 caries-active adolescents of both sexes who volunteered for participation
      giving an informed consent. The study has a randomised placebo-controlled double
      blind pilot design with two parallel arms. After a 2-week run-in period, the
      subjects were instructed to drink 2.5 dl of milk supplemented with Lactobacillus
      rhamnosus LB21 (107 CFU/ml) (test) or standard control milk (placebo) once daily
      for a period of 2 weeks (intervention period). Samples of stimulated whole saliva
      and supragingival plaque were collected at baseline (after run-in) and
      immediately after the end of the intervention period (follow-up). The salivary
      levels of mutans streptococci and lactobacilli were estimated by conventional
      culturing on selective agar plates. The presence and level of 19 oral species
      associated with the caries process were determined using the checkerboard DNA-DNA
      hybridisation technique. Differences between the groups were assessed using the
      non-parametric Wilcoxon-Mann-Whitney and chi-square tests. RESULTS: The mean
      caries experience was high with an average of 7.0 +/- 3.8 proximal enamel
      lesions. The most prevalent dominating species in the plaque samples were
      Streptococcus mitis, Veillonella parvula and Streptococcus gordonii. The saliva
      samples displayed a more mixed profile, with Streptococcus mitis, Rothia
      dentocariosa, Lactobacillus casei and Lactobacillus curvata being frequently
      identified species. All of the subjects harboured mutans streptococci in their
      saliva, with 61% of them colonised with salivary lactobacilli. No statistically
      significant differences in the microbial profiles or the estimated counts between
      the baseline and follow-up samples, or between the two study groups, were
      observed. CONCLUSIONS: The present study showed that a short-term daily intake of
      milk supplemented with the probiotic bacterium L. rhamnosus LB21 did not
      significantly affect the microbial profiles or the levels of caries-associated
      bacteria in saliva and supragingival plaque samples collected from caries-active
      adolescents.

PMID- 21180678
TI  - Periodontal and gingival parameters in young adults with acute myeloid leukaemia
      in Kerala, South India.
AB  - PURPOSE: Patients presenting with leukaemic blast crisis with acute myeloid
      leukaemia (AML) may have gingival enlargements that interfere with oral hygiene.
      Few large cohort studies of gingival lesions have been carried out on AML
      patients. The aim of the present study was to assess gingival and periodontal
      pathology at the time of presentation, prior to chemotherapy, in a cohort of
      adult patients presenting at a cancer hospital in Kerala, a region located in
      southern India. MATERIALS AND METHODS: A total of 73 young adult patients (mean
      age 20.6 +/- 2.3) who were diagnosed with AML were examined. These patients did
      not suffer from any other systemic disorder. The oral hygiene status, gingival
      overgrowth (GO) and periodontal status were assessed using traditional clinical
      indices. RESULTS: Around three-quarters of the patients had either fair or poor
      oral hygiene. A statistically significant association between dental plaque
      levels and both GO and periodontal index (P < 0.001) was observed. CONCLUSIONS:
      Poor oral hygiene is a risk factor for leukaemic GO and for destructive
      periodontal disease. Both conditions add to the microbial burden these patients
      are exposed to. In patients showing high levels of oral hygiene, the GO tends to
      be mild and does not seem to be problematic, especially with respect to
      mechanical tooth cleaning.

PMID- 21180677
TI  - Hyaluronan-containing mouthwash as an adjunctive plaque-control agent.
AB  - PURPOSE: Hyaluronan, commonly known as hyaluronic acid, has been shown to have
      anti-inflammatory action, bacteriostatic effect and antioxidant properties, thus
      making its use as a long-term anti-plaque and anti-gingivitis agent an appealing
      proposition. The aim of the present study was to evaluate the efficacy of 0.025%
      hyaluronan-containing mouthwash in comparison with 0.2% chlorhexidine and a water
      based mouthwash and also to evaluate its antibacterial efficacy on isolated
      strains of periodontopathogens. MATERIALS AND METHODS: Forty-five volunteers in a
      hospital setting were recruited. A single-blinded, parallel design, randomised
      controlled trial was carried out and the 4-day plaque re-growth model was used to
      study the efficacy of the three mouthwashes. Microbiological and clinical
      evaluation was performed by culturing and using dental indices, respectively. The
      three mouthwashes used in the present study were commercially available 0.025%
      sodium hyaluronate, 0.2% chlorhexidine and a water-based rinse (negative
      control). Effects of the three mouthwashes were tested on the growth of isolated
      strains of Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans
      (Aa) and Prevotella intermedia (Pi). RESULTS: In vitro, hyaluronan had a distinct
      effect on the growth of Aa and Pi with no effect on the growth of Pg. In vivo,
      the differences between the individual rinse solutions and the water-based
      solution showed significantly less plaque regrowth with respect to both
      chlorhexidine (P = 0.033) and hyaluronan (P = 0.045) when compared to the
      negative control. The difference between chlorhexidine and hyaluronan was not
      statistically significant (P = 0.69). CONCLUSIONS: Hyaluronan (0.025%)-containing
      mouthwash was comparable to chlorhexidine (0.2%) in inhibiting plaque growth in
      vivo, and it significantly reduced the growth of Aa and Pi in vitro

PMID- 21180679
TI  - Furcation entrance dimensions of the first and second mandibular molars among
      Jordanians.
AB  - PURPOSE: The complexity of molar furcation areas provides a challenge for
      periodontal treatment that leads to more tooth loss when compared to other tooth
      types. Furcation entrance dimension (FED) of molar teeth affects treatment
      outcomes and prognosis considerably. The aim of the present study was to
      determine the FED in first and second mandibular molars among Jordanian adults
      and to assess the relationship to gender. MATERIALS AND METHODS: The sample
      consisted of 430 first and second mandibular molars that were extracted in four
      dental clinics of the Ministry of Health. The teeth were sorted according to
      gender after extraction and those meeting the following conditions were selected:
      intact crowns with completely preserved cementoenamel junction, intact furcation
      areas and roots lacking restorations. The FEDs were measured under magnification
      using a computer system (AutoCad 2005) equipped with a digital camera (HP
      Photosmart). RESULTS: A high percentage (63.5%) of FEDs were wider than 0.75 mm,
      with buccal furcations wider than lingual ones and first molar furcations having
      wider furcations than those of second molars among Jordanian adults. A
      significant difference in the mean FEDs between male and female patients was
      observed in the second molar. CONCLUSIONS: Furcation involvements in Jordanian
      adults are more suitable for treatment with standard hand curettes than those
      reported in other cultures, as a high percentage (63.5%) of the FEDs were wider
      than the width of a standard Gracey curette blade. A significant difference
      between sexes in the second molar was observed. The use of other instruments,
      such as ultrasonic devices, should be taken into account during scaling and root
      planing as about 37.5% of the furcation would not be adequately instrumented with
      standard curettes.

PMID- 21180681
TI  - Immediate positioning of a definitive abutment versus repeated abutment
      replacements in post-extractive implants: 3-year follow-up of a randomised
      multicentre clinical trial.
AB  - PURPOSE: The aim of this randomised clinical trial was to evaluate the influence
      of restoration on marginal bone loss (MBL) using immediately definitive abutments
      (one abutment-one time concept) versus provisional abutments later replaced by
      definitive abutments. MATERIALS AND METHODS: In three private clinics, 32
      patients with 32 hopeless maxillary premolars were selected for post-extractive
      implant-supported immediate restoration and randomised to provisional abutment
      (PA) and definitive abutment (DA) groups, 16 sites in each group. After tooth
      extraction, 7 patients had to be excluded for buccal wall fracture at tooth
      extraction or lack of sufficient primary implant stability (< 35 Ncm). The
      remaining 25 patients (10 PA, 15 DA) received a post-extractive wide-diameter
      implant. Immediately after insertion, the PA group were immediately restored
      using a platform-switched provisional titanium abutment. In the DA group,
      definitive platform-switched titanium abutments were tightened. In both groups,
      provisional crowns were adapted, avoiding occlusal contacts. All implants were
      definitively restored after 3 months. In the PA group, a traditional impression
      technique with coping transfer was adopted, dis/reconnecting abutments several
      times; in the DA group, metal prefabricated copings were used and final
      restorations were seated, avoiding abutment disconnection. Digital standardised
      periapical radiographs using a customised film holder were recorded at baseline
      (T0 = implant insertion), final restoration (T1 = 3 months later), and at 18
      month (T2) and 3-year (T3) follow-ups. The MBL was evaluated with a computerised
      measuring technique and digital subtraction radiography (DSR) software was used
      to evaluate radiographic density. RESULTS: At the 3-year follow-up a success rate
      of 100% in both groups was reported. In the PA group, peri-implant bone
      resorption was 0.36 mm at T1, 0.43 mm at T2, and 0.55 mm at T3. In the DA group,
      peri-implant bone resorption was 0.35 mm at T1, 0.33 mm at T2, and 0.34 mm at T3.
      Statistically significant lower bone losses were found at T2 (0.1 mm) and T3 (0.2
      mm) for the DA group. At T3, significantly higher DSR values around implant necks
      were recorded in the DA group (72 +/- 5.0) when compared with the PA group (52 +/
      9.5). CONCLUSIONS: The current trial suggests that the 'one abutment-one time'
      concept might be a possible additional strategy in post-extraction immediately
      restored platform-switched single implants to further minimise peri-implant
      crestal bone resorption, although a 0.2 mm difference may not have any clinical
      effect. Additional clinical trials with larger groups of patients should be
      performed to better investigate this hypothesis.

PMID- 21180682
TI  - Sinus lift with guided bone regeneration or anorganic bovine bone: 1-year post
      loading results of a pilot randomised clinical trial.
AB  - PURPOSE: To compare the efficacy of two different techniques for maintaining the
      space beneath a maxillary lining lifted using a lateral window approach: rigid
      synthetic resorbable barriers versus granular anorganic bovine bone. MATERIALS
      AND METHODS: Ten partially edentulous patients having bilaterally 1 to 5 mm of
      residual bone height and at least 5 mm bone width below the maxillary sinuses,
      were randomised in a split-mouth study design, to receive a rigid Inion GTR
      Biodegradable Membrane System barrier without any graft on one side and 100%
      loosely packed granular Bio-Oss on the contralateral side following a lateral
      window, two-stage, sinus lift procedure. After 6 months, two or three implants
      were inserted at each side and submerged for 4 months. Implants were loaded with
      provisional acrylic prostheses and replaced, after 4 months, by definitive metal
      ceramic prostheses cemented with provisional cement. Outcome measures were
      implant and prosthetic failures, any complication and peri-implant marginal bone
      level changes assessed by a blinded outcome assessor. All patients were followed
      up to 1 year after loading. RESULTS: One patient dropped out after implant
      placement. One distal implant failed at the Inion side just before delivery of
      the definitive prosthesis, which was cut and maintained as a single crown. Four
      complications occurred in three patients at Inion sites (two sinus lining
      perforations, one fracture of the ceramic cusp of the definitive prosthesis, one
      iatrogenic peri-implantitis) versus two complications at Bio-Oss sites (one sinus
      lining perforation and one iatrogenic peri-implantitis). There were no
      differences for failures or complications between groups; however, in one of the
      patients where a perforation occurred at the Inion site, at implant placement,
      the sinus was filled two-thirds with soft tissue and the site was retreated with
      Bio-Oss. There were no statistically significant differences in bone loss between
      groups. One year after loading, Inion sides lost an average of 1.5 mm of
      periimplant bone and Bio-Oss sides about 1.7 mm. CONCLUSIONS: A bone graft may
      not be needed to augment atrophic maxillary sinuses since it is sufficient to
      keep space with a rigid barrier; however, it may be simpler to fill sinuses with
      a bone substitute than positioning a rigid barrier to maintain space.

PMID- 21180683
TI  - Outcome of dental implants in patients with and without a history of
      periodontitis: a 5-year pragmatic multicentre retrospective cohort study of 1727
      patients.
AB  - AIM: To evaluate the outcome of dental implants placed in patients with a history
      of periodontitis. Patients with no or mild history of periodontitis served as
      controls. MATERIALS AND METHODS: A total of 1727 patients were consecutively
      treated in four private practices. Patients were divided into three groups
      according to their initial periodontal conditions assessed with a modified
      periodontal screening and recording (PSR) index: 630 patients were in the severe
      periodontitis (SP) group, 839 in the moderate periodontitis (MP) group, and 258
      had no periodontitis (NP). Patients requiring periodontal treatment were treated
      prior to implantation. Various implant systems and procedures were used. In
      total, 3260 implants and 1707 implant-supported prostheses were placed in the SP
      group, 2813 implants and 1744 implant-supported prostheses in the MP group, and
      647 implants and 424 implant-supported prostheses in the NP group. Mixed implant
      tooth supported prostheses (98 prostheses in 89 patients) were not considered.
      Outcome measures were prosthesis and implant survival. RESULTS: Two-hundred and
      fifty patients were lost to follow-up 5 years after loading. Regarding prosthesis
      failures, 13 prostheses could not be placed or failed in 13 patients of the SP
      group (0.8%), 11 prostheses could not be placed or failed in 9 patients of the MP
      group (0.7%), and 3 prostheses failed in 3 patients of the NP group (0.9%). For
      implant failures, 130 (4.5%) implants failed in the SP group, 74 (3.1%) implants
      failed in the MP group, and 15 (3.0%) implants failed in the NP group. Most of
      the implant failures (90%) occurred before implant loading. Fitting a logistic
      regression for early implant failures and total implant failures, taking into
      account the clustering of implants in patients, there were no statistically
      significant differences between the three PSR groups (P > 0.05). CONCLUSIONS:
      Owing to the retrospective nature of this study, conclusions need to be
      interpreted with caution. A previous history of periodontal disease may not have
      a significant impact on implant failures up to 5 years after loading.

PMID- 21180684
TI  - Clinical evaluation of Tiny(r) 2.5- and 3.0-mm narrow-diameter implants as
      definitive implants in different clinical situations: a retrospective cohort
      study.
AB  - AIM: The aim of the present study was to assess retrospectively the survival of
      narrow-diameter implants (2.5 and 3 mm in diameter) in patients with insufficient
      bone ridge thickness for placement of standard-diameter implants. MATERIAL AND
      METHODS: Fifty-one patients with 89 inserted narrow-diameter implants (2.5 and
      3.0 mm) were included. Patients were treated with one or more narrow-diameter
      implants between June 2004 and December 2005. The observation period for all
      included implants was at least 3 years after implant loading. Outcome measures
      were implant survival, complications and marginal bone level changes evaluated on
      panoramic radiographs. RESULTS: The mean follow-up period for all implants was 48
      months. Only one implant was lost, yielding survival rates of 98.9% and 98.0% for
      the implant- and subject-based analyses, respectively. Six complications were
      reported. Twenty-four months after implant insertion, mean bone loss was 1.26 mm
      (SD 0.51). CONCLUSIONS: Narrow-diameter implants can be successfully used to
      treat narrow bone ridges up to 3 years after loading.

PMID- 21180685
TI  - Immediate function of four zygomatic implants: a 1-year report of a prospective
      study.
AB  - PURPOSE: To evaluate the clinical outcome of maxillary prostheses supported by
      four immediately loaded zygomatic implants after 1 year of function. MATERIALS
      AND METHODS: Seventeen patients were consecutively included and followed up to 1
      year after prosthetic loading. Patients had severely atrophic maxillae (Cawood
      and Howell classification C-VI and D-V or D-VI) and were rehabilitated using four
      immediately loaded zygomatic implants, two in each zygoma bone. Outcome measures
      were success rates of the prostheses, of the zygomatic implants, complications
      and oral health-related quality of life (OHRQoL). RESULTS: No patients dropped
      out. No zygomatic implants were lost, although one implant could not be used
      because it was placed in an unfavourable position. The orbital cavity was
      penetrated during the drilling procedure in one patient with no relevant clinical
      consequences. One patient experienced an infection followed by a fistula in one
      zygomatic implant, which was successfully treated. The average score from the
      OHIP-14 questionnaire was 3.4, which is similar to that of the general
      population. CONCLUSIONS: The present study suggests that four immediately loaded
      zygomatic implants can be used to rehabilitate patients with severely atrophied
      maxillae.

PMID- 21180690
TI  - The ab initio calculation of molecular electric, magnetic and geometric
      properties.
AB  - We give an account of some recent advances in the development of ab initio
      methods for the calculation of molecular response properties, involving electric,
      magnetic, and geometric perturbations. Particular attention is given to
      properties in which the basis functions depend explicitly both on time and on the
      applied perturbations such as perturbations involving nuclear displacements or
      external magnetic fields when London atomic orbitals are used. We summarize a
      general framework based on the quasienergy for the calculation of arbitrary-order
      molecular properties using the elements of the density matrix in the atomic
      orbital basis as the basic variables. We demonstrate that the necessary perturbed
      density matrices of arbitrary order can be determined from a set of linear
      equations that have the same formal structure as the set of linear equations
      encountered when determining the linear response equations (or time-dependent
      self-consistent-field equations). Additional components needed to calculate
      properties involving perturbation-dependent basis sets are flexible one- and two
      electron integral techniques for geometric or magnetic-field differentiated
      integrals; in Kohn-Sham density-functional theory (KS-DFT), we also need to
      calculate derivatives of the exchange-correlation functional. We describe a
      recent proposal for evaluating these contributions based on automatic
      differentiation. Within this framework, it is now possible to calculate any
      molecular property for an arbitrary self-consistent-field reference state,
      including two- and four-component relativistic self-consistent-field wave
      functions. Examples of calculations that can be performed with this formulation
      are presented.

PMID- 21180691
TI  - The impact of a rice based diet on urinary arsenic.
AB  - Rice is elevated in arsenic (As) compared to other staple grains. The Bangladeshi
      community living in the United Kingdom (UK) has a ca. 30-fold higher consumption
      of rice than white Caucasians. In order to assess the impact of this difference
      in rice consumption, urinary arsenicals of 49 volunteers in the UK (Bangladeshi n
      = 37; white Caucasians n = 12) were monitored along with dietary habits. Total
      urinary arsenic (As(t)) and speciation analysis for dimethylarsinic acid (DMA),
      monomethylarsonic acid (MA) and inorganic arsenic (iAs) was conducted. Although
      no significant difference was found for As(t) (median: Bangladeshis 28.4 ug L(
      1)) and white Caucasians (20.6 ug L(-1)), the sum of medians of DMA, MA and iAs
      for the Bangladeshi group was found to be over 3-fold higher (17.9 ug L(-1)) than
      for the Caucasians (3.50 ug L(-1)). Urinary DMA was significantly higher (p <
      0.001) in the UK Bangladeshis (median: 16.9 ug DMA L(-1)) than in the white
      Caucasians (3.16 ug DMA L(-1)) as well as iAs (p < 0.001) with a median of 0.630
      ug iAs L(-1) for Bangladeshi and 0.250 ug iAs L(-1) for Caucasians. Cationic
      compounds were significantly lower in the Bangladeshis (2.93 ug L(-1)) than in
      Caucasians (14.9 ug L(-1)). The higher DMA and iAs levels in the Bangladeshis are
      mainly the result of higher rice consumption: arsenic is speciated in rice as
      both iAs and DMA, and iAs can be metabolized, through MA, to DMA by humans. This
      study shows that a higher dietary intake of DMA alters the DMA/MA ratio in urine.
      Consequently, DMA/MA ratio as an indication of methylation capacity in
      populations consuming large quantities of rice should be applied with caution
      since variation in the quantity and type of rice eaten may alter this ratio.

PMID- 21180693
TI  - BET specific surface area and pore structure of MOFs determined by hydrogen
      adsorption at 20 K.
AB  - Low-pressure high-resolution hydrogen adsorption for the metal-organic framework
      MIL-101 are measured at 19.5 K and pressures below 57 kPa. The BET specific
      surface area and micropore volume are determined and compared to results from
      nitrogen adsorption at 77 K. Steps in the hydrogen adsorption isotherm are
      correlated to the pore structure of MIL-101.

PMID- 21180694
TI  - Preparation of a specific monoclonal antibody to asiaticoside for the development
      of an enzyme-linked immunosorbent assay.
AB  - Asiaticoside (AS), the major active component of Centella asiatica (L.) Urban, is
      used as a memory enhancer and for wound healing. We have successfully prepared
      monoclonal antibodies (MAbs) against AS, and developed an enzyme-linked
      immunosorbent assay (ELISA) system for its determination. AS was conjugated to
      the carrier protein bovine serum albumin (BSA), which acted as an immunogen. In
      order to confirm its immunogenicity, the ratio of hapten in the AS-BSA conjugate
      was determined by matrix-assisted laser desorption/ionization time of flight mass
      spectrometry (MALDI-TOF MS). After immunization, hybridomas secreting MAbs
      against AS were produced by fusing splenocytes with the mouse myeloma cell line,
      SP2/0-Ag14. After the screening, anti-asiaticoside MAb 2B4 was obtained. Weak
      cross-reactivities occurred with madecassoside (7.08%), but no cross-reactivities
      were observed with other related triterpenoid glycosides (<0.01%). The assay was
      suitable for quantitating AS in the range of 0.78 to 50 ug mL(-1). A good
      correlation of AS concentrations in crude extracts of C. asiatica between ELISA
      and HPLC methods was obtained (r(2) = 0.999). The contents of AS in various
      cultivated C. asiatica samples were assayed by the newly established ELISA. The
      recovery rates of AS in the samples were in the range of 95-103% with
      coefficients of variation of <10%. The intra- and inter-assay variations were 3.9
      and 4.5%, respectively. The ELISA method described should prove useful as an
      analytical tool for quality control and standardization of medicinal plants and
      pharmaceutical products containing AS.

PMID- 21180695
TI  - Mixed-valence manganese calcium oxides as efficient catalysts for water
      oxidation.
AB  - Incorporation of calcium to mixed-valence manganese oxides improved the water
      oxidation activity of these manganese oxides.

PMID- 21180696
TI  - Polyoxometalate (POM)-based, multi-functional, inorganic-organic, hybrid
      compounds: syntheses and molecular structures of silanol- and/or siloxane bond
      containing species grafted on mono- and tri-lacunary Keggin POMs.
AB  - Using 3-mercaptopropyltrimethoxysilane (HS(CH2)3Si(OMe)3) as a silane-coupling
      agent (SCA), mono- and tri-lacunary Keggin polyoxometalate (POM)-based, multi
      functional, inorganic-organic, hybrid compounds, (Et4N)3[alpha
      PW11O39{(HS(CH2)3Si)2O}] EtN-1 (the 1 : 2 complex of a POM unit and organosilyl
      groups), (Bu4N)3[A-PW9O34(HS(CH2)3SiOH)3] BuN-2 (the 1 : 3 complex) and (Bu4N)3[A
      alpha-PW9O34(HS(CH2)3SiO)3(Si(CH2)3SH)] BuN-3 (the 1 : 4 complex) were
      synthesized and unequivocally characterized by elemental analysis,
      thermogravimetric and differential thermal analyses (TG/DTA), FTIR, solid-state
      (29Si and 31P) CPMAS NMR, solution (29Si, 31P, 1H and 13C) NMR, and X-ray
      crystallography. [Note: The moieties of their polyoxoanions are abbreviated
      simply as 1-3, respectively.] The X-ray molecular structures of EtN-1 and BuN-3
      were determined. In EtN-1, two organic groups connected through a siloxane bond (
      Si-O-Si- bond) were grafted on a mono-lacunary site of a Keggin POM, whereas in
      BuN-3 four organic groups connected through siloxane bonds were grafted on a tri
      lacunary site of a Keggin POM. In BuN-2, three organic groups were grafted in the
      form of silanol (-SiOH) on a tri-lacunary site, i.e., in BuN-2 there was no
      siloxane bond. BuN-3 was synthesized as BuN-3a and BuN-3b by two methods,
      respectively; (1) BuN-3a was obtained by a 1 : 1 molar-ratio reaction of BuN-2
      and an SCA in CH3CN, and (2) BuN-3b was prepared by a direct 1 : 4 molar-ratio
      reaction of a tri-lacunary Keggin POM and SCA in water-CH3CN. X-Ray
      crystallography revealed that BuN-3a is the same as BuN-3b. It is probable that
      BuN-2 is an intermediate in the formation of BuN-3. Terminal -SH groups in 1-3,
      as well as -OH groups in 2, can be utilized for immobilization of POMs and, also,
      as building blocks for the formation of novel hybrid compounds.

PMID- 21180697
TI  - A molecular clip throws new light on the complexes formed by a family of cyclam
      cored dendrimers with Zn(II) ions. Efficient energy transfer in the heteroleptic
      complexes.
AB  - Complexation of Zn(II) ions by cyclam cored dendrimers appended with four (G0),
      eight (G1) and 16 naphthyl chromophores (G2) at the periphery have been
      investigated in CH3CN-CH2Cl2 1 : 1 (v/v) solution by absorption and emission, ESI
      mass and 1H NMR spectroscopy. The results obtained can be interpreted by the
      formation of complexes of 2 : 1 dendrimer to metal stoichiometry, at low metal
      ion concentration, and 1 : 1 complexes upon further addition of Zn(II) ions, for
      all the dendrimer generations. Upon addition of a molecular clip C2- consisting
      of two anthracene sidewalls bridged by a benzene group with two sulfate
      substituents in the para positions, heteroleptic complexes of general formula
      [GnZnC] are formed. Interestingly, in these complexes, a very efficient quenching
      (practically 100%) of the dendrimer naphthyl luminescence and sensitization (ca.
      90%) of the clip anthracene emission take place. The complex [G2ZnC] exhibits a
      very high molar absorption coefficient in the UV spectral region owing to the 16
      naphthyl chromophores of the dendrimer and the two anthracene units of the clip
      (epsilon = 1.7 * 105 M-1 cm-1 at 263 nm). Furthermore, the excitation energy
      absorbed by the naphthyl chromophores is efficiently funneled to the two
      anthracene units of the clip, which emits in the blue spectral region.

PMID- 21180698
TI  - Toward sensitive, quantitative point-of-care testing (POCT) of protein markers:
      miniaturization of a homogeneous time-resolved fluoroimmunoassay for prostate
      specific antigen detection.
AB  - Point-of-care testing (POCT) systems which allow for a sensitive, quantitative
      detection of protein markers are extremely useful for the early detection and
      therapy progress monitoring of cancer. However, currently commercially available
      POCT devices are mainly limited to the qualitative detection of protein markers.
      In this study we demonstrate the successive miniaturization of a sensitive and
      fast assay for the quantitative detection of prostate-specific antigen (PSA)
      using a well established and clinically approved homogeneous time-resolved
      fluoroimmunoassay technology (TRACE(r)) on a commercial plate-reader system
      (KRYPTOR(r)). Regarding the initial requirements for the development of POCT
      devices we applied a 30-fold assay volume reduction (150 uL to 5 uL) to achieve a
      reasonable lab-on-a-chip volume and a 24-fold and 120-fold excitation pulse
      energy reduction to achieve reasonable pulse energies for low-cost miniature
      excitation sources. Due to highly efficient optimization of key POCT parameters
      our miniaturized PSA assay achieved a 30% increased sensitivity and a 2-fold
      improved limit of detection compared to the standard plate-reader method. Our
      results demonstrate the successful implementation of key parameters for a
      significant miniaturization and for cost reduction in the clinically approved
      KRYPTOR(r) platform for protein detection. The technological alterations required
      are easy-to-implement and can be immediately adapted for more than 30 diagnostic
      protein markers already available for the KRYPTOR(r) platform. These features
      strongly recommend our assay format to be utilized in innovative, sensitive,
      quantitative POCT of protein markers.

PMID- 21180699
TI  - Diffusion in ternary aqueous systems containing human serum albumin and
      precipitants of different classes.
AB  - The mutual diffusion coefficients for two aqueous ternary systems, both
      containing a protein, human serum albumin (HSA, component 1), were measured. The
      first system contained a neutral polymer, polyethylene glycol (PEG, component 2),
      and the second an "organic solvent", 2-methyl-2,4-pentanediol (MPD, component 3).
      Both PEG and MPD are used as co-precipitants in HSA crystallization protocols.
      Measurements were performed at constant protein concentration, with increasing
      precipitant content. The results obtained for the two systems were discussed and
      compared. In both cases, the two main diffusion coefficients, relative to the
      motion of the protein and of the precipitant under their own concentration
      gradient, can be interpreted in terms of non-specific volume interactions between
      the solutes. Particularly, it was showed that any possible direct HSA-MPD
      interaction may not have a significant effect on the values of these two
      diffusion coefficients. Differences arise between the cross precipitant's
      diffusion coefficients, relative to the motion of the precipitant under the
      protein concentration gradient, D(i1) with i = 2, 3. In the case of PEG, the
      D(21) trend vs. c(2) can be simply interpreted in terms of an "exclude volume"
      effect. In contrast, in the case of MPD, the D(31)vs. c(3) trend seems to
      indicate a more complex mechanism of transport. Because the cross precipitant's
      diffusion coefficient plays an important role in the crystallization process, the
      implication of the observed difference on the crystallization procedure was also
      discussed.

PMID- 21180700
TI  - Dichloro organosilicon bismuthanes as precursors for rare compounds with a
      bismuth-pnictogen or bismuth-tellurium bond.
AB  - The chloro-bridged interpnictogen compounds [tBu2PhSiE{BiClCH(SiMe3)2}2] (E = P
      (4), As (5)) can be synthesized by the reaction of [tBu2PhSiELi2] (E = P (2), As
      (3)) with (Me3Si)2CHBiCl2 in a molar ratio of 1 : 2. The reaction of
      iPr3SiAs(SiMe3)2 with (Me3Si)2CHBiCl2 yields the analogous compound
      [iPr3SiAs{BiClCH(SiMe3)2}2] (6) as well as the diarsine species
      [As{BiClCH(SiMe3)2}2]2 (7). Preparation of 7 is also possible in the reaction of
      As(SiMe3)3 with (Me3Si)2CHBiCl2. Starting from (Me3Si)3SiTeSiMe3, the Bi/Te
      compounds [{(Me3Si)3SiTe}2BiR] (R = CH(SiMe3)2 (8), C(SiMe3)3 (9)) are obtained
      by the reaction with RBiCl2 (R = CH(SiMe3)2, C(SiMe3)3 (1)). The intermediate and
      final products are characterized by multinuclear NMR spectroscopy and IR
      spectroscopy. Furthermore, crystal structures determined by X-ray diffraction are
      described for compounds 1 and 3-9.

PMID- 21180702
TI  - First metal complexes of 6,6'-dihydroxy-2,2'-bipyridine: from molecular wires to
      applications in carbonylation catalysis.
AB  - The first square planar rhodium(I) complexes containing the 6,6'-dihydroxy-2,2'
      bipyridine ligand have been prepared. The complexes form molecular wires in the
      solid state and are active catalysts for the carbonylation of methyl acetate.

PMID- 21180701
TI  - A novel asymmetric di-Ni(II) system as a highly efficient functional model for
      phosphodiesterase: synthesis, structures, physicochemical properties and
      catalytic kinetics.
AB  - A novel asymmetric phenol-based 'end-off' dinucleating ligand 2-{[(2
      piperidylmethyl)amino]methyl}-4-bromo-6-[(1-methylhomopiperazine-4
      yl)methyl]phenol (HL) and three dinuclear nickel(II) complexes, [Ni2L(MU-OH)]
      (ClO4)2 (1), [Ni2L(DNBA)2(CH3CN)2]BPh4 (2) and [Ni2L(BPP)2(CH3CN)2]BPh4 (3) have
      been synthesized and characterized by a variety of techniques including: NMR,
      infrared and UV-vis spectroscopies, mass spectrometry, elemental analysis, molar
      conductivity, thermal analysis, magnetochemistry and single-crystal X-ray
      diffractometry. The UV-vis spectrum of complex 1 exhibits a strong peak at 510
      nm, a characteristic absorption of a d-d transition of the square-planar four
      coordinated Ni(II) center. Utilizing this feature, the stepwise formation of mono
      and dinickel centers in solution can be monitored. Phosphodiesterase activity of
      a dinuclear Ni(II) system (complex 1), formed in situ by a 2 : 1 mixture of
      Ni(2+) ions and the ligand HL, was investigated using bis(4-nitrophenyl)phosphate
      (BNPP) as the substrate. The pH dependence of the BNPP cleavage in water-ethanol
      (1 : 1, v/v) reveals a bell-shaped pH-k(obs) profile with an optimum at about pH
      8.3 which is parallel to the formation of the dinuclear species [Ni2L(MU
      OH)](2+), according to the increase of the peak at 510 nm in the UV-vis
      absorption spectrum . These studies reveal that the di-Ni(II) system shows the
      highest catalytic activity reported so far, with an acceleration rate 1.28 * 107
      times faster than the uncatalyzed reaction. The bridging hydroxyl group in
      [Ni2L(MU-OH)](2+) is responsible for the hydrolysis reaction. The possible
      mechanism for the BNPP cleavage promoted by di-Ni(II) system is proposed on the
      basis of kinetic and spectral analyses. This study provides a less common example
      of the asymmetric phosphodiesterase model, which is like the active sites of most
      native metallohydrolases.

PMID- 21180703
TI  - Suspended microchannel resonators with piezoresistive sensors.
AB  - Precision frequency detection has enabled the suspended microchannel resonator
      (SMR) to weigh single living cells, single nanoparticles, and adsorbed protein
      layers in fluid. To date, the SMR resonance frequency has been determined
      optically, which requires the use of an external laser and photodiode and cannot
      be easily arrayed for multiplexed measurements. Here we demonstrate the first
      electronic detection of SMR resonance frequency by fabricating piezoresistive
      sensors using ion implantation into single crystal silicon resonators. To
      validate the piezoresistive SMR, buoyant mass histograms of budding yeast cells
      and a mixture of 1.6, 2.0, 2.5, and 3.0 um diameter polystyrene beads are
      measured. For SMRs designed to weigh micron-sized particles and cells, the mass
      resolution achieved with piezoresistive detection (~3.4 fg in a 1 kHz bandwidth)
      is comparable to what can be achieved by the conventional optical-lever detector.
      Eliminating the need for expensive and delicate optical components will enable
      new uses for the SMR in both multiplexed and field deployable applications.

PMID- 21180704
TI  - Alkene isomerization/enamide-ene and diene metathesis for the construction of
      indoles, quinolines, benzofurans and chromenes with a chiral cyclopropane
      substituent.
AB  - A synthetic method for bicyclic heterocycles, such as indole, benzofuran and
      chromene derivatives bearing a chiral cyclopropane at the 2-position, was
      established using isomerization of a terminal olefin and enamide-ene or diene
      metathesis. This route can also be applied to chiral 2-cyclopropylquinoline
      synthesis (both cis and trans).

PMID- 21180705
TI  - Identification of methicillin-resistant Staphylococcus aureus-specific peptides
      for targeted photoantimicrobial chemotherapy.
AB  - The increasing prevalence of multi-drug resistant bacteria, such as methicillin
      resistant Staphylococcus aureus (MRSA), necessitates development of alternative
      modes of bacterial targeting which are not hindered by antibiotic resistance and
      minimise collateral damage. To achieve this, the FliTrxTM bacterially-displayed
      peptide library was panned against MRSA and randomly selected clones (n = 20)
      were DNA sequenced. One selected peptide was synthesised as both cyclic and
      linear constructs. Binding of the cyclic construct was observed by flow cytometry
      against isolates of MRSA whilst the linear construct showed low affinity. Low
      reactivity was observed with other Staphylococcal sp., gram-negative bacteria and
      human keratinocytes. The selected peptide was also cloned in-frame, within the
      thioredoxin gene into the pPROTet.E 6xHN vector for protein expression. A
      porphyrin photosensitiser (5-(4-isothiocyanatophenyl)-10,15,20-tris(4-N
      methylpyridiniumyl)porphyrin trichloride) was conjugated to the recombinant
      protein and the in vitro cytotoxic effect of the resulting bioconjugate was
      determined against MRSA and other non-specific bacterial and mammalian cell
      lines. Photoantimicrobial chemotherapy (PACT) using the bioconjugate showed a 66%
      reduction in MRSA growth in comparison with non-irradiated cells. This work
      demonstrates the potential to isolate peptides with binding specificity against
      MRSA that can be used for targeted PACT, providing an effective alternative to
      antibody targeting.

PMID- 21180706
TI  - Blue fluorescent dye-protein complexes based on fluorogenic cyanine dyes and
      single chain antibody fragments.
AB  - Fluoromodules are complexes formed upon the noncovalent binding of a fluorogenic
      dye to its cognate biomolecular partner, which significantly enhances the
      fluorescence quantum yield of the dye. Previously, several single-chain, variable
      fragment (scFv) antibodies were selected from a yeast cell surface-displayed
      library that activated fluorescence from a family of unsymmetrical cyanine dyes
      covering much of the visible and near-IR spectrum. The current work expands our
      repertoire of genetically encodable scFv-dye pairs by selecting and
      characterizing a group of scFvs that activate fluorogenic violet-absorbing, blue
      fluorescing cyanine dyes, based on oxazole and thiazole heterocycles. The dye
      binds to both yeast cell surface-displayed and soluble scFvs with low nanomolar
      K(d) values. These dye-protein fluoromodules exhibit high quantum yields,
      approaching unity for the brightest system. The promiscuity of these scFvs with
      other fluorogenic cyanine dyes was also examined. Fluorescence microscopy
      demonstrates that the yeast cell surface-displayed scFvs can be used for
      multicolor imaging. The prevalence of 405 nm lasers on confocal imaging and flow
      cytometry systems make these new reagents potentially valuable for cell
      biological studies.

PMID- 21180707
TI  - Defining rules of aromaticity: a unified approach to the Huckel, Clar and Randic
      concepts.
AB  - The molecular structure of any system may be unambiguously described by its
      adjacency matrix, A, in which bonds are assigned entry a(ij) = 1 and non-bonded
      pairs of atoms entry a(ij) = 0. For pi-electron-containing conjugated
      hydrocarbons, this matrix may be modified in order to represent one of the
      possible Kekule structures by assigning entry 1 to double bonds and entry 0 to
      single bonds, leading to the Kekule matrix K which can be obtained from the A
      matrix by subtracting 1 from elements a(pq) that represent single bonds in the
      Kekule structure. The A and K matrices are the boundary cases of a general matrix
      A(epsilon), named perturbation matrix, in which from elements a(pq) that
      represent single bonds is subtracted a value epsilon?<0,1> representing the
      magnitude of the perturbation. The determinant of the A(epsilon) matrix is
      unambiguously represented by an appropriate polynomial that, in turn, can be
      written in a form containing terms +/-(1-epsilon)(N/2) that identify types of pi
      electron conjugated cycles (N is the corresponding number of pi-electrons). If
      the sign before the term is (+), then the contribution is stabilizing, but if it
      is (-) the contribution is destabilizing. The approach shows why and how the
      Huckel rule works, how the Randic conjugated circuits result from the analysis of
      canonical structures, and also how the Clar rule may be extended to include
      aromatic cycles larger than six-membered (aromatic sextet).

PMID- 21180708
TI  - Progress on lanthanide-based organic-inorganic hybrid phosphors.
AB  - Research on organic-inorganic hybrid materials containing trivalent lanthanide
      ions (Ln(3+)) is a very active field that has rapidly shifted in the last couple
      of years to the development of eco-friendly, versatile and multifunctional
      systems, stimulated by the challenging requirements of technological applications
      spanning domains as diverse as optics, environment, energy, and biomedicine. This
      tutorial review offers a general overview of the myriad of advanced Ln(3+)-based
      organic-inorganic hybrid materials recently synthesised, which may be viewed as a
      major innovation in areas of phosphors, lighting, integrated optics and optical
      telecommunications, solar cells, and biomedicine.

PMID- 21180709
TI  - Dynamics and origin of PM2.5 during a three-year sampling period in Beijing,
      China.
AB  - Systematic sampling and analysis were performed to investigate the dynamics and
      the origin of suspended particulate matter smaller than 2.5 MUm in diameter
      (PM(2.5)), in Beijing, China from 2005 to 2008. Identifying the source of PM(2.5)
      was the main goal of this project, which was funded by the German Research
      Foundation (DFG). The concentrations of 19 elements, black carbon (BC) and the
      total mass in 158 weekly PM(2.5) samples were measured. The statistical
      evaluation of the data from factor analysis (FA) identifies four main sources
      responsible for PM(2.5) in Beijing: (1) a combination of long-range transport
      geogenic soil particles, geogenic-like particles from construction sites and the
      anthropogenic emissions from steel factories; (2) road traffic, industry
      emissions and domestic heating; (3) local re-suspended soil particles; (4) re
      suspended particles from refuse disposal/landfills and uncontrolled dumped waste.
      Special attention has been paid to seven high concentration "episodes", which
      were further analyzed by FA, enrichment factor analysis (EF), elemental
      signatures and backward-trajectory analysis. These results suggest that long
      range transport soil particles contribute much to the high concentration of
      PM(2.5) during dust days. This is supported by mineral analysis which showed a
      clear imprint of component in PM(2.5). Furthermore, the ratios of Mg/Al have been
      proved to be a good signature to trace back different source areas. The Pb/Ti
      ratio allows the distinction between periods of predominant anthropogenic and
      geogenic sources during high concentration episodes. Backward-trajectory analysis
      clearly shows the origins of these episodes, which partly corroborate the FA and
      EF results. This study is only a small contribution to the understanding of the
      meteorological and source driven dynamics of PM(2.5) concentrations.

PMID- 21180710
TI  - Biophysical alteration of the secretory track in beta-cells due to molecular
      overcrowding: the relevance for diabetes.
AB  - Recent data demonstrate that accumulation of misfolded proteins within the early
      part of the secretory track of beta-cells causes impaired insulin synthesis and
      development of diabetes. The molecular mechanism of this cellular dysfunction
      remains largely unknown. Using basic molecular principles and computer
      simulations, we suggested recently that hyperglycemic conditions can generate
      substantial molecular crowding effects in the secretory track of beta-cells
      leading to significant alterations of the insulin biosynthesis capabilities.
      Here, we review the major molecular mechanisms that may be implicated in the
      alteration of insulin synthesis in susceptible beta-cells. Steric repulsions and
      volume exclusion in the endoplasmic reticulum (ER) increase the propensity of
      misfolding of proinsulin (the precursor molecule of insulin). In addition,
      similar forces might act in the next secretory compartments (Golgi and vesicles)
      leading to (i) altered packaging of proinsulin in vesicles (ii) entrapment of
      proinsulin convertases and/or restricted accessibility for these convertases to
      the cleavage sites on the surface of the proinsulin and (iii) depressed kinetic
      rate of the transformation of the native proinsulin in active insulin and C
      peptide. These concepts are expressed in simple mathematical terms relating the
      kinetic coefficient of proinsulin to insulin conversion to the levels of
      proinsulin misfolding and hyperglycemic stress. The present approach is useful
      for understanding molecular phenomena associated with the pathogenesis of
      diabetes. It also offers practical means for predicting the state of pancreatic
      beta-cells from measurements of the insulin to proinsulin ratio in the blood.
      This is of immediate clinical relevance and may improve the diagnosis of
      diabetes.

PMID- 21180714
TI  - Vitalising porous inorganic silica networks with organic functions--PMOs and
      related hybrid materials.
AB  - Mesoporous organic-inorganic hybrid materials are an interesting class of
      materials, which combine the advantages of two worlds; the inorganic part builds
      a robust substrate while organic functions make them alive in a way that they can
      be potentially used in a number of applications. In this tutorial review, we
      provide an overview of how mesoporous materials are synthesised via the 'soft
      template' path and how the incorporation of organic functions can be achieved.
      Furthermore, a colourful survey full of examples is presented, providing a small
      overview of field of applications that can potentially benefit from the use of
      periodic mesoporous organosilicas (PMOs) and related materials.

PMID- 21180715
TI  - A proteomic approach to study parathyroid glands.
AB  - Parathyroid tumours are heterogeneous and in some cases the diagnosis may be
      difficult using histological features. In this study we used a two-dimensional
      electrophoresis (2D)/mass spectrometry (MS)-based approach to examine the global
      changes of parathyroid adenoma tissues protein profile compared to the
      parathyroid normal tissues. Validation of protein expression was performed by
      immunoblotting using specific antibodies. Ingenuity software was used to identify
      the biological processes to which these proteins belong and to construct a
      potential network. A total of 30 proteins were found to be differentially
      expressed, of which 22 resulted in being over-expressed. Proteins identified by
      2D/MS/MS proteomics were classified into functional categories and a major change
      (>= 2-fold) in terms of expression was found in proteins involved in response to
      biotic stimuli, cell organization and signal transduction. After Ingenuity
      analysis, 14-3-3 zeta/delta appears to be a key protein in the network of
      parathyroid adenoma, where it is linked to other proteins such as annexin A2, B
      box and SPRY domain-containing protein (BSPRY), p53 and epidermal growth factor
      receptor (EGFR). Our results suggest that the proteomic approach was able to
      differentiate the protein profiles of normal parathyroid and parathyroid adenoma
      and identify a panel of proteins which are differentially expressed. The
      functional role of these proteins in the network of intracellular pathways is
      discussed.

PMID- 21180716
TI  - Amino functionalized zeolitic tetrazolate framework (ZTF) with high capacity for
      storage of carbon dioxide.
AB  - A three dimensional -NH(2) functionalized Zeolitic Tetrazolate Framework (ZTF-1)
      has been reported. The framework adopts a dia topology (M-L-M angle is close to
      156 degrees ). ZTF-1 shows high CO(2) (273 K) and H(2) (77 K) uptake due to the
      presence of the free -NH(2) group and uncoordinated tetrazolate nitrogen.

PMID- 21180717
TI  - The tightly regulated copper window in yeast.
AB  - The two opposing yeast copper regulators, Ace1 and Mac1, were converted into two
      fluorescent probes, Ace1-FRET and Mac1-FRET, which selectively and sensitively
      respond to Cu(+). The Cu(+)-binding curves obtained for both regulators as well
      as for the copper storage proteins Cup1 and Crs5 show that free copper(i) is
      maintained in a narrow window inside yeast.

PMID- 21180718
TI  - Synthesis and characterization of small circular double-stranded RNAs.
AB  - Small circular double-stranded RNAs (dsRNAs) were synthesized. The structural
      analysis by atomic force microscopy gave direct images for the interpretation of
      the structural strain present in circular dsRNAs. Finally, we demonstrated that
      circular dsRNA caused RNAi effect in cells.

PMID- 21180719
TI  - Hollow polymer particles that are pH-responsive and redox sensitive: two simple
      steps to triggered particle swelling, gelation and disassembly.
AB  - A new, simple, two-step method is introduced for preparing hollow particles that
      are both pH-responsive and redox sensitive. Hollow poly(methyl methacrylate-co
      methacrylic acid) particles swell at moderate pH values, form gels in
      concentrated dispersions and can be disassembled by adding reducing agents.

PMID- 21180720
TI  - Ammonium ylides for the diastereoselective synthesis of glycidic amides.
AB  - A highly trans-selective protocol for the synthesis of glycidic amides was
      developed. This approach gave access to oxiranes by reacting stabilised ammonium
      ylides bearing an alpha-carbonyl group and aromatic aldehydes in moderate to good
      yields.

PMID- 21180721
TI  - The role of hydrogen bonding in water-metal interactions.
AB  - The hydrogen bond interaction between water molecules adsorbed on a Pd <111>
      surface, a nucleator of two dimensional ordered water arrays at low temperatures,
      is studied using density functional theory calculations. The role of the exchange
      and correlation density functional in the characterization of both the hydrogen
      bond and the water-metal interaction is analyzed in detail. The effect of non
      local correlations using the van der Waals density functional proposed by Dion et
      al. [M. Dion, H. Rydberg, E. Schroder, D. C. Langreth and B. I. Lundqvist, Phys.
      Rev. Lett., 2004, 92, 246401] is also studied. We conclude that the choice of
      this potential is critical in determining the cohesive energy of water-metal
      complexes. We show that the interaction between water molecules and the metal
      surface is as sensitive to the density functional choice as hydrogen bonds
      between water molecules are. The reason for this is that the two interactions are
      very similar in nature. We make a detailed analogy between the water-water bond
      in the water dimer and the water-Pd bond at the Pd <111> surface. Our results
      show a strong similarity between these two interactions and based on this we
      describe the water-Pd bond as a hydrogen bond type interaction. These results
      demonstrate the need to obtain an accurate and reliable representation of the
      hydrogen bond interaction in density functional theory.

PMID- 21180722
TI  - Electrochemical control of adsorption dynamics of surface layer proteins on gold.
AB  - The kinetics and mechanism of the adsorption of the surface layer proteins of
      Lysinibacillus sphaericus CCM2177 on gold depend on the charging conditions of
      the electrochemical double layer and the addition of Ca(2+) ions. The electrical
      and mass charging was monitored by an in situ electrochemical quartz
      microbalance. Adsorption and monolayer formation of the protein molecules occur
      in the positive potential region where solvated anions form the electrochemical
      double layer. The crystalline character of the surface layer was diagnosed by an
      atomic force microscope. Negative of the point of zero charge, multilayer island
      structures were found.

PMID- 21180723
TI  - Fullerene derivative acceptors for high performance polymer solar cells.
AB  - Polymer solar cells (PSCs) are composed of a blend film of a conjugated polymer
      donor and a soluble fullerene derivative acceptor sandwiched between a PEDOT :
      PSS coated ITO positive electrode and a low workfunction metal negative
      electrode. The conjugated polymer donor and the fullerene derivative acceptor are
      the key photovoltaic materials for high performance PSCs. For the acceptors,
      although [6,6]-phenyl-C(61)-butyric acid methyl ester (PC(60)BM) and its
      corresponding C(70) derivative PC(70)BM are dominantly used as the acceptors in
      PSC at present, several series of new fullerene derivatives with higher-lying
      LUMO energy level and better solubility were reported in recent years for further
      improving the power conversion efficiency of the PSCs. In this perspective paper,
      we reviewed the recent research progress on the new fullerene derivative
      acceptors, including various PC(60)BM-like C(60) derivatives, PC(60)BM bisadduct,
      PC(70)BM bisadduct, indene-C(60) bisadduct and indene-C(70) bisadduct,
      trimetallic nitride endohedral fullerenes and other C(60) derivatives with multi
      side chains. The synthesis and physicochemical properties of PC(60)BM and
      PC(70)BM were also introduced considering the importance of the two fullerene
      acceptors.

PMID- 21180724
TI  - Are ab initio quantum chemistry methods able to predict vibrational states up to
      the dissociation limit for multi-electron molecules close to spectroscopic
      accuracy?
AB  - The aim of the study was to explore the limits of ab initio methods towards the
      description of excited vibrational levels up to the dissociation limit for
      molecules having more than two electrons. To this end a high level ab initio
      potential energy function was constructed for the four-electron LiH molecule in
      order to accurately predict a complete set of bound vibrational levels
      corresponding to the electronic ground state. It was composed from: (a) an ab
      initio non-relativistic potential obtained at the MR-CISD level including size
      extensivity corrections and quintuple-sextuple zeta extrapolation of the basis,
      (b) MVD relativistic corrections obtained at icMR-CISD/cc-pwCV5Z level, and (c)
      DBOC obtained at the MR-CISD/cc-pwCVTZ level. Finally, the importance of non
      adiabatic effects was also tested by using atomic masses in the vibrational
      kinetic energy operator. The calculated vibrational levels were compared with
      those obtained from experimental data [J. A. Coxon and C. S. Dickinson, J. Chem.
      Phys., 2004, 121, 9378]. Our best estimate of the potential curve results in
      vibrational energies with a RMS deviation of only ~1 cm(-1) for the entire set of
      all empirically determined vibrational levels known so far. These results
      represent a drastic improvement over previous theoretical predictions of
      vibrational levels of (7)LiH up to dissociation, D(0), which was predicted to be
      19,594 cm(-1).

PMID- 21180725
TI  - Kinetic studies of atmospherically relevant silicon chemistry. Part III:
      Reactions of Si+ and SiO+ with O3, and Si+ with O2.
AB  - Silicon ions are generated in the Earth's upper atmosphere by hyperthermal
      collisions of material ablated from incoming meteoroids with atmospheric
      molecules, and from charge transfer of silicon-bearing neutral species with major
      atmospheric ions. Reported Si(+) number density vs. height profiles show a sharp
      decrease below 95 km, which has been commonly attributed to the fast reaction
      with H(2)O. Here we report rate coefficients and branching ratios of the
      reactions of Si(+) and SiO(+) with O(3), measured using a flow tube with a laser
      ablation source and detection of ions by quadrupole mass spectrometry. The
      results obtained are (2sigma uncertainty): k(Si(+) + O(3), 298 K) = (6.5 +/- 2.1)
      * 10(-10) cm(3) molecule(-1) s(-1), with three product channels (branching
      ratios): SiO(+) + O(2) (0.52 +/- 0.24), SiO + O(2)(+) (0.48 +/- 0.24), and
      SiO(2)(+) + O (<0.1); k(SiO(+) + O(3), 298 K) = (6 +/- 4) * 10(-10) cm(3)
      molecule(-1) s(-1), where the major products (branching ratio >= 0.95) are SiO(2)
      + O(2)(+). Reactions (1) and (2) therefore have the unusual ability to neutralise
      silicon directly, as well as forming molecular ions which can undergo
      dissociative recombination with electrons. These reactions, along with the
      recently reported reaction between Si(+) and O(2)((1)Delta(g)), largely explain
      the disappearance of Si(+) below 95 km in the atmosphere, relative to other major
      meteoric ions such as Fe(+) and Mg(+). The rate coefficient of the Si(+) + O(2) +
      He reaction was measured to be k(298 K) = (9.0+/-1.3) * 10(-30) cm(6) molecule(
      2) s(-1), in agreement with previous measurements. The SiO(2)(+) species produced
      from this reaction, which could be vibrationally excited, is observed to charge
      transfer at a relatively slow rate with O(2), with a rate constant of k(298 K) =
      (1.5 +/- 1.0) * 10(-13) cm(3) molecule(-1) s(-1).

PMID- 21180726
TI  - The active site structure of nitrided and oxynitrided graphite as a cathode
      catalyst in a fuel cell.
AB  - The first-principles studies were performed for the modified graphites with
      various edge conformations, which revealed that the NH edge facilitates easy
      transfer of an electron into the adsorbed O(2).

PMID- 21180727
TI  - New insight in the template decomposition process of large zeolite ZSM-5
      crystals: an in situ UV-Vis/fluorescence micro-spectroscopy study.
AB  - A combination of in situ UV-Vis and confocal fluorescence micro-spectroscopy was
      used to study the template decomposition process in large zeolite ZSM-5 crystals.
      Correlation of polarized light dependent UV-Vis absorption spectra with confocal
      fluorescence emission spectra in the 400-750 nm region allowed extracting
      localized information on the nature and amount of chemical species formed upon
      detemplation at the single particle level. It has been found by means of
      polarized light dependent UV-Vis absorption measurements that the progressive
      growth of molecules follows the orientation of the straight channels of ZSM-5
      crystals. Oligomerizing template derivatives lead to the subsequent build-up of
      methyl-substituted benzenium cations and more extended coke-like species, which
      are thermally stable up to ~740 K. Complementary confocal fluorescence emission
      spectra showed nearly equal distribution of these molecules within the entire
      volume of the thermally treated zeolite crystals. The strongest emission bands
      were appearing in the orange/red part of the visible spectrum, confirming the
      presence of large polyaromatic molecules.

PMID- 21180728
TI  - Why hybrid porous solids capture greenhouse gases?
AB  - Hybrid porous solids, with their tunable structures, their multifunctional
      properties and their numerous applications, are currently topical, particularly
      in the domain of adsorption and storage of greenhouse gases. Most of the data
      reported so far concern the performances of these solids in this domain,
      particularly in terms of adsorbed amounts of gas but do not explain at the atomic
      level why and how adsorption and storage occur. From a combination of structural,
      spectroscopic, thermodynamic experiments and of molecular simulations, this
      tutorial review proposes answers to these open questions with a special emphasis
      on CO(2) and CH(4) storage by some rigid and flexible hybrid porous materials.

PMID- 21180729
TI  - Facile synthesis of metal oxide/reduced graphene oxide hybrids with high lithium
      storage capacity and stable cyclability.
AB  - We report an environment-friendly approach to synthesize transition metal oxide
      nanoparticles (NPs)/reduced graphene oxide (rGO) sheets hybrids by combining the
      reduction of graphene oxide (GO) with the growth of metal oxide NPs in one step.
      Either Fe2O3 or CoO NPs were grown onto rGO sheets in ethanol solution through a
      solvothermal process, during which GOs were reduced to rGO without the addition
      of any strong reducing agent, e.g. hydrazine, or requiring any post-high
      temperature annealing process. The GO or rGO during the precipitation of metal
      oxide NPs may act as heterogeneous nucleation seeds to facilitate the formation
      of small crystal grains. This may allow more efficient diffusion of Li ions and
      lead to high specific capacities. These metal oxide NPs-rGO hybrids were used as
      anodes for Li-ion batteries, which showed high capacities and excellent charge
      discharge cycling stability in the voltage window between 0.01 and 3.0 V. For
      example, Fe2O3 NPs/rGO hybrids showed specific capacity of 881 mA h g(-1) in the
      90th cycle at a discharge current density of 302 mA g(-1) (0.3 C), while CoO
      NPs/rGO hybrids showed a lower capacity of 600 mA h g(-1) in the 90th cycle at a
      discharge current density of 215 mA g(-1) (0.3 C). These nanohybrids also show
      excellent capacities at high C rate currents, e.g. 611 mA h g(-1) for Fe2O3/rGO
      sample in the 300th cycle at 2014 mA g(-1) (2 C). Such synthesis technique can be
      a promising route to produce advanced electrode materials for Li-ion batteries.

PMID- 21180730
TI  - Catalytic dioxygen activation by Co(II) complexes employing a coordinatively
      versatile ligand scaffold.
AB  - The ligand bis(2-isobutyrylamidophenyl)amine has been prepared and used to
      stabilize both mononuclear and dinuclear cobalt(II) complexes. The nuclearity of
      the cobalt product is regulated by the deprotonation state of the ligand. Both
      complexes catalytically oxidize triphenylphosphine to triphenylphosphine oxide in
      the presence of O(2).

PMID- 21180731
TI  - Ionogels, ionic liquid based hybrid materials.
AB  - The current interest in ionic liquids (ILs) is motivated by some unique
      properties, such as negligible vapour pressure, thermal stability and non
      flammability, combined with high ionic conductivity and wide electrochemical
      stability window. However, for material applications, there is a challenging need
      for immobilizing ILs in solid devices, while keeping their specific properties.
      In this critical review, ionogels are presented as a new class of hybrid
      materials, in which the properties of the IL are hybridized with those of another
      component, which may be organic (low molecular weight gelator, (bio)polymer),
      inorganic (e.g. carbon nanotubes, silica etc.) or hybrid organic-inorganic (e.g.
      polymer and inorganic fillers). Actually, ILs act as structuring media during the
      formation of inorganic ionogels, their intrinsic organization and physicochemical
      properties influencing the building of the solid host network. Conversely, some
      effects of confinement can modify some properties of the guest IL, even though
      liquid-like dynamics and ion mobility are preserved. Ionogels, which keep the
      main properties of ILs except outflow, while allowing easy shaping, considerably
      enlarge the array of applications of ILs. Thus, they form a promising family of
      solid electrolyte membranes, which gives access to all-solid devices, a topical
      industrial challenge in domains such as lithium batteries, fuel cells and dye
      sensitized solar cells. Replacing conventional media, organic solvents in lithium
      batteries or water in proton-exchange-membrane fuel cells (PEMFC), by low-vapour
      pressure and non flammable ILs presents major advantages such as improved safety
      and a higher operating temperature range. Implementation of ILs in separation
      techniques, where they benefit from huge advantages as well, relies again on the
      development of supported IL membranes such as ionogels. Moreover,
      functionalization of ionogels can be achieved both by incorporation of organic
      functions in the solid matrix, and by encapsulation of molecular species (from
      metal complexes to enzymes) in the immobilized IL phase, which opens new routes
      for designing advanced materials, especially (bio)catalytic membranes, sensors
      and drug release systems (194 references).

PMID- 21180733
TI  - Magnetic field effects on exciplex-forming systems: the effect on the locally
      excited fluorophore and its dependence on free energy.
AB  - This study addresses magnetic field effects in exciplex forming donor-acceptor
      systems. For moderately exergonic systems, the exciplex and the locally excited
      fluorophore emission are found to be magneto-sensitive. A previously introduced
      model attributing this finding to excited state reversibility is confirmed.
      Systems characterised by a free energy of charge separation up to approximately 
      0.35 eV are found to exhibit a magnetic field effect on the fluorophore. A simple
      three-state model of the exciplex is introduced, which uses the reaction distance
      and the asymmetric electron transfer reaction coordinate as pertinent variables.
      Comparing the experimental emission band shapes with those predicted by the
      model, a semi-quantitative picture of the formation of the magnetic field effect
      is developed based on energy hypersurfaces. The model can also be applied to
      estimate the indirect contribution of the exchange interaction, even if the
      perturbative approach fails. The energetic parameters that are essential for the
      formation of large magnetic field effects on the exciplex are discussed.

PMID- 21180732
TI  - Nanoscale morphology dependent pseudocapacitance of NiO: Influence of
      intercalating anions during synthesis.
AB  - Three nano-porous NiO samples with high specific surface area were prepared by a
      simple hydrothermal method under homogeneous precipitation conditions using CTAB
      as a template and urea as the hydrolysis controlling agent. This study was done
      to determine the effect of different anions (acetate, nitrate and chloride)
      present in the precursor salts on the morphology and pseudocapacitance behavior
      of NiO. The samples were characterized by thermogravimetry (TG), differential
      scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Brunauer-Emmet
      Teller (BET) isotherm and field emission scanning electron microscopy (FESEM).
      The final NiO samples showed different hierarchical surface morphologies and
      their effect on the electrochemical pseudocapacitance behavior was carefully
      studied by cyclic voltammetry, galvanostatic charge-discharge cycles
      (chronopotentiometry) and impedance spectroscopic techniques. The specific
      capacitance of NiO sample synthesized by NO3- ion intercalation showed higher
      surface area, intermediate porosity and a novel pine-cone morphology with nano
      wire surface attachments. This sample exhibits the highest pseudocapacitance of
      279 F g(-1) at a scan rate of 5 mV s(-1), calculated from the cyclic voltammetry
      measurements. The sample synthesized by Cl- intercalation shows a nano-flower
      morphology with lower surface area, porosity and pseudocapacitance behaviour. The
      NiO sample prepared in the presence of CH3COO- ions showed a honeycomb type
      surface morphology with an intermediate pseudocapacitance value but higher
      reversibility. The galvanostatic charge-discharge and impedance spectroscopic
      measurements on these NiO electrodes were consistent with CV results. The
      Coulombic efficiency of all the three NiO samples was found to be high (~85 to
      ~99%) after 100 galvanostatic charge-discharge cycles. This study shows that the
      surface morphology and porosity of NiO are strongly influenced by the anions in
      the precursor salts, and in turn affect significantly the pseudocapacitance
      behavior and the power performance of NiO powders.

PMID- 21180734
TI  - An outsider's perspective--ecotaxis revisited: an integrative review of cancer
      environment, iron and immune system cells.
AB  - Lymphoid cell and tumor cell migration share similarities: 1. migration to
      specific microenvironments; 2. increased microvasculature with increased growth;
      3. cell division. At the same time, contrasting aspects between the two merit
      attention: 1. failure of tumors to return to microvasculature quiescence; 2.
      failure of malignant cells to stop dividing; 3. failure of tumor cells to re
      enter the circulation after returning to a non-activated phenotype. Analysis of
      these contrasting aspects leads to the reviewing of unexpected roles of immune
      cells in the tumor environment, recent work on ferroportin expression with lack
      of iron export by tumor cells, iron export by M2 macrophages, and deficient
      dendritic cells (DCs) in the tumor environment. DCs in lymph nodes have recently
      been found to bring lymph node vasculature to quiescence after antigen
      stimulation. Contrary to current dogma, the evidence is that some immune system
      cells in the tumor environment may be favoring regulators instead of diminishing
      tumor growth. In addition, recent data herein reviewed will make it difficult not
      to consider iron and iron gene expression as relevant components of the tumor
      environment. Finally, I conclude with wondering how much longer what I call the
      'Hunter Paradigm' will dominate cancer research and immunology and how timely it
      is to acknowledge in the first decade of a new century, Mina Bissell as a pioneer
      in the change of that paradigm in Cancer Research. "Suppose he'd listened to the
      erudite committee; He would have only found where not to look" WH Auden.

PMID- 21180735
TI  - Crystal structure and carrier transport properties of a new 3D mixed-valence
      Cu(I)-Cu(II) coordination polymer including pyrrolidine dithiocarbamate ligand.
AB  - A novel mixed-valence Cu(i)-Cu(ii) coordination polymer having an infinite three
      dimensional (3D) structure, {[Cu(I)(4)Cu(II)(2)Br(4)(Pyr-dtc)(4)].CHCl(3)}(n) (1)
      (Pyr-dtc(-) = pyrrolidine dithiocarbamate), has been prepared and structurally
      characterized via X-ray diffraction. This complex consists of 1D Cu(i)-Br chains
      and bridging mononuclear copper(ii) units of Cu(II)(Pyr-dtc)(2), which form an
      infinite 3D network. A magnetic study indicates that this complex includes
      copper(ii) ions exhibiting a weak antiferromagnetic interaction (theta = -0.086
      K) between the unpaired electrons of the copper(ii) ions present in the
      diamagnetic Cu(i)-Br chains. The carrier transport properties of 1 are
      investigated using an impedance spectroscopy technique and flash-photolysis time
      resolved microwave conductivity measurement (FP-TRMC). The impedance spectroscopy
      reveals that this complex exhibits intriguing semiconducting properties at a
      small activation energy (E(a) = 0.29 eV (bulk)). The sum of the mobilities of the
      negative and positive carriers estimated via FP-TRMC is SigmaMU~ 0.4 cm(2) V(-1)
      s(-1).

PMID- 21180737
TI  - A versatile reagent to synthesize diverse ionic liquids ranging from small
      molecules and dendrimers to functionalized proteins.
AB  - An ionic liquid "reagent" bearing a succinimidyl activated ester is reported that
      can be used to synthesize a variety of small molecule and macromolecular ionic
      liquids. In addition, the ionic liquid reagent was used to modify lysozyme, and
      the protein retained its structure and function after modification. This study
      describes a facile and reliable route to new ionic liquid compositions.

PMID- 21180738
TI  - Fullerene-templated synthesis of a cyclic porphyrin trimer using olefin
      metathesis.
AB  - An olefination approach to the construction of covalently linked cyclic
      metalloporphyrin trimers is presented using fullerenes such as C(60) or C(70) as
      a template. Yields of the trimer approach 60%. In the absence of a template, the
      major product is the cyclic dimer (50% yield) with only a small amount of trimer
      (<10%) formed, indicating this is a template-directed approach.

PMID- 21180739
TI  - A convenient, high-sensitivity approach to multiple-resonance NMR at nanolitre
      volumes with inductively-coupled micro-coils.
AB  - We propose using singly-tuned MU-coils and (1)H-detection to obtain high
      sensitivity in lieu of miniaturizing cumbersome multi-resonance circuits, with
      the existing MAS probe circuitry/coil providing RF at other frequencies. We
      demonstrate two key building blocks in solid-state NMR: cross-polarization and
      heteronuclear decoupling. As well, a (1)H-detected 2D HMQC is obtained.

PMID- 21180740
TI  - High performance single-crystal field-effect transistors based on twisted
      polyaromatic semiconductor pyreno[4,5-a]coronene.
AB  - A novel p-channel semiconductor pyreno[4,5-a]coronene has been synthesized and
      characterized. The highly fused pi-conjugated framework has a twisted geometry
      with an excellent on-top cofacial pi-pi stacking in the crystal structure and
      with a centroid-to-centroid distance of 3.808 A. Single-crystal field effect
      transistors based on the molecule exhibit a high mobility of ~0.89 cm(2) V(-1) s(
      1) and an on/off ratio of ~6 * 10(4).

PMID- 21180741
TI  - Carbohydrate assisted fluorescence turn-on gluco-imino-anthracenyl conjugate as a
      Hg(II) sensor in milk and blood serum milieu.
AB  - A new anthracenyl-imino-glucosyl conjugate (L) selectively senses Hg(2+) by turn
      on fluorescence with a 13 +/- 1 fold enhancement by forming a 2 : 1 complex in pH
      5 to 10 even in the presence of several biologically and ecologically relevant
      metal ions, with a 25 +/- 2% fluorescence enhancement at the EPA limit of 2 ppb.
      L is equally sensitive towards Hg(2+) in the presence of albumin proteins and in
      blood serum and milk.

PMID- 21180742
TI  - Density functional modelling of silicate and aluminosilicate dimerisation
      solution chemistry.
AB  - Common throughout sol-gel chemistry, including zeolite synthesis, aluminosilicate
      glass formation and geopolymerisation, is the process of inorganic oxide
      polymerisation and deprotonation. In this investigation, some of the fundamental
      reactions occurring during zeolite synthesis and geopolymerisation at high pH are
      investigated using density functional theory (DFT), and are compared with: (i)
      existing values reported in the literature, and (ii) new and previously published
      DFT-derived data for similar silicate reactions at near-neutral pH. From the
      results it is seen that the energetics of deprotonation and dimerisation
      reactions depend greatly on the pH value, and these results correlate well with
      existing experimental values and trends. Hence, this investigation exemplifies
      that an accurate replication of the solution environment is crucial for obtaining
      useful theoretical results for species dissolved in non-ideal environments.

PMID- 21180743
TI  - Purification-free synthesis of a highly efficient ruthenium dye complex for dye
      sensitised solar cells (DSSCs).
AB  - A novel Ru(II) sensitiser A597 containing the 4,4'-dioctylamido-2,2'-bipyridine
      ancillary ligand is synthesised without the need for purification steps. It shows
      an irreversible oxidation at 0.92 V in the cyclic voltammogram and an absorbtion
      at 539 nm in the UV-vis spectrum corresponding to an (1)MLCT transition.
      Preliminary DFT calculations reveal that the HOMO is localised on the ruthenium
      metal centre and the thiocyanate ligands, whereas the LUMO is predominantly on
      the 4,4'-carboxy-2,2'-bipyridine ligand. The ruthenium complex exhibits a maximum
      power conversion efficiency (7.25%) compared with the known Z907 (8.32%) in dye
      sensitised solar cells.

PMID- 21180744
TI  - A stable droplet reactor for high temperature nanocrystal synthesis.
AB  - We report a versatile capillary-based droplet reactor for the controlled
      synthesis of nanoparticles over a wide range of flow conditions and temperatures.
      The reactor tolerates large flow-rate differentials between individual reagent
      streams, and allows droplet composition to be varied independently of residence
      time and volume. The reactor was successfully applied to the synthesis of metal
      (Ag), metal-oxide (TiO(2)) and compound semiconductor (CdSe) nanoparticles, and
      in each case exhibited stable droplet flow over many hours of operation without
      fouling, even for reactions involving solid intermediates. For CdSe formed by the
      reaction of Cd oleate and Se, highly controlled growth could be achieved at
      temperatures of up to 250  degrees C, with emission spectra varying smoothly and
      reproducibly with temperature and flow-rate. The droplet reactor showed
      exceptional stability when operated under constant flow-rate and temperature
      conditions, yielding particles with well-defined band-edge emission spectra that
      did not vary over the course of a full day's continuous operation.

PMID- 21180745
TI  - Transition metal mediated construction of pyrrole ring on 2,3-dihydroquinolin
      4(1H)-one: synthesis and pharmacological evaluation of novel tricyclic
      heteroarenes.
AB  - A facile two-step method for the construction of fused pyrrole ring leading to 5
      substituted 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinolin-1-ones via C-C followed by
      intramolecular C-N bond forming reaction is described. In vitro pharmacological
      evaluation and molecular modelling studies of some of the compounds synthesized
      are presented.

PMID- 21180747
TI  - Observation of a two-dimensional halogen-bonded cocrystal at sub-monolayer
      coverage using synchrotron X-ray diffraction.
AB  - The formation of two-dimensional halogen-bonded layers of 4,4'-bipyridyl and 1,4
      diiodotetrafluorobenzene was observed on a graphite surface at sub-monolayer
      coverage using synchrotron X-ray diffraction; the use of the diffraction
      technique enabled, for the first time, the measurement of I...N halogen bonding
      distances in a two-dimensional cocrystal and the identification of the halogen
      bonding interaction in the monolayer.

PMID- 21180746
TI  - Solar UV exposure of primary schoolchildren in Valencia, Spain.
AB  - To quantify schoolchildren's exposure to ultraviolet erythemal radiation (UVER),
      personal dosimeters (VioSpor) were used to measure biologically effective
      ultraviolet (UV) radiation received in the course of their daily school
      activities. The study took place in two primary schools in Valencia (39 degrees
      28'N), Spain, for several weeks from March 2008 until May 2009, with two age
      groups (6-8 years and 10-11 years) and involved about 47 schoolchildren. The
      median daily UV exposure values for all age groups and solar height intervals
      considered in the study ranged from 1.31 to 2.11 standard erythemal doses (SEDs).
      Individual UV exposure was analyzed as a function of age, gender and dosimeter
      position. Significant statistical differences were found between different age
      groups, with the younger age group receiving higher statistically significant
      UVER exposure. It was also found that boys received significantly higher UVER
      exposure than girls. It was also noted that shoulder dosimeters registered higher
      readings than wrist dosimeters. Exposure ratio (ER) is defined as the ratio
      between the personal dose on a selected anatomical site and the corresponding
      ambient dose on a horizontal plane. The median ER for all age groups and solar
      height intervals in the study range from 4.5% to 10.7%, with higher values at
      lower solar heights.

PMID- 21180748
TI  - Functional, star polymeric molecular carriers, built from biodegradable
      microgel/nanogel cores.
AB  - Acid and disulfide biodegradable cross-linkers have been employed to generate
      microgel star polymers, using RAFT-polymer arms. RAFT end-groups were then
      exploited to attach functional compounds via both thiol-ene and thiol-pyridyl
      disulfide exchange reactions.

PMID- 21180749
TI  - C-H activation of 2,4,6-triphenylphosphinine: unprecedented formation of
      cyclometalated [(P^C)Ir(III)] and [(P^C)Rh(III)] complexes.
AB  - An unprecedented C-H activation of 2,4,6-triphenylphosphinine by Ir(III) and
      Rh(III) has been observed. Time-dependent (31)P{(1)H} NMR spectroscopy gave
      insight into the cyclometalation reaction and the corresponding coordination
      compounds were characterized by means of X-ray crystallography. In contrast,
      2,4,6-triphenylpyridine does not show any ortho-metalation, demonstrating a
      remarkable difference in reactivity between these two structurally related
      aromatic heterocycles.

PMID- 21180750
TI  - The competitive adsorption of counter-ions at the surface of anionic surfactants
      solution.
AB  - We have determined the surface excess of surface active anion and counter-ions in
      a non-aqueous polar solution of anionic surfactants blends, as well as their
      distributions near the solution surface. The blends of two anionic surfactants,
      sodium dodecyl sulfate (SDS) and cesium dodecyl sulfate (CDS), with different
      contents were used as solutes to prepare the solutions. According to the
      isotherms that are separately fitted to the pure SDS and the pure CDS solutions
      (C. Wang and H. Morgner, Langmuir, 2010, 26, 3121), CDS has a slightly but
      significantly higher surface excess than SDS (CDS is 14.8% higher) at the
      concentration of 0.04 molal kg(-1) solvent. Therefore, in this work we chose 0.04
      molal kg(-1) solvent as total anion concentration and varied the contents of
      surfactants. From present experimental results, we found that the surface excess
      of anion increases slightly with the CDS in the bulk content. Importantly, the
      fractions of Cs(+) in cationic surface excess are higher than its contents in the
      bulk for all three solutions. This demonstrates that Cs(+) is more competitive
      than Na(+) in the adsorption. The surface structure of the solutions have been
      characterized by concentration-depth profiles, of Cs(+), Na(+) and of sulfur
      which is used to identify dodecyl sulfate. Those profiles evidence that Cs ions
      penetrate deeper than sodium ions into the layer formed by the heads of the
      anions, reducing the electrical potential of the surface more efficiently. This
      can be used to explain the adsorption competition between those two counter-ions.
      The cause that makes Cs(+) more competitive than Na(+) in the adsorption can be
      attributed to its less tightly bound solvation shell, and thus, to its
      effectively smaller ion size.

PMID- 21180751
TI  - Templated growth of platinum nanowheels using the inhomogeneous reaction
      environment of bicelles.
AB  - Novel platinum nanowheels were synthesized by the reduction of aqueous platinum
      complex with ascorbic acid in the presence of disk-like bicelles. The platinum
      nanowheels possess thickened centers and flared edges that are connected by
      dendritic platinum nanosheets. This structural complexity can be attributed to
      the inhomogeneous micro-environment of the templating bicelles consisting of a
      central bi-layer region and a high curvature rim. The formation mechanism of the
      nanowheels was investigated by imaging nanostructures at different stages of the
      reaction. The templating bicelles were also imaged by TEM with the aid of
      negative staining. The variation of reaction parameters including platinum
      concentration, temperature, and total concentration of surfactants (CTAB + FC7)
      led to other types of platinum nanostructures, such as circular dendritic
      nanosheets with a tunable diameter and rectangular dendritic nanosheets.
      Interestingly, under irradiation by a TEM electron beam, the dendritic nanosheet
      portion of the nanowheels transforms into a metastable holey sheet. In addition,
      the platinum nanowheels have an electrochemical active surface area comparable to
      that of ETEK platinum black and thus are expected to have potential applications
      in catalysis.

PMID- 21180752
TI  - [1,2,3]Triazolo[1,5-a]pyridyl phosphines reflecting the influence of phosphorus
      lone pair orientation on spectroscopic properties.
AB  - A series of new triazolopyridine-based phosphines has been prepared. These
      compounds revealed unexpected spectroscopic patterns. In particular, the NMR
      spectra are highly dependent on the relative conformational preference of the
      phosphine substituent at C7. Here, we report on their complete NMR analysis, X
      ray structures and DFT calculations that confirm the particular arrangement of
      the phosphorus lone pair orbital related to the substituent pattern of the chosen
      phosphine.

PMID- 21180753
TI  - Synthesis, crystal structure and magnetic properties of an oxalato-bridged
      Re(IV)Mo(VI) heterobimetallic complex.
AB  - The Re(IV)-Mo(VI) compound of formula (PPh(4))(2)[ReCl(4)(MU-ox)MoO(2)Cl(2)] (1)
      constitutes the first example of a heterodinuclear oxalato-bridged complex in the
      coordination chemistry of molybdenum.

PMID- 21180754
TI  - Reactive spin state dependent enantiospecific photocyclization of axially chiral
      alpha-substituted acrylanilides.
AB  - The enantiomeric ratio (e.r.) in the 3,4-dihydroquinolin-2-one photoproduct
      during 6pi-photocyclization of alpha-substituted axially chiral ortho-tert-butyl
      acrylanilides depends on the nature of the reactive spin state (singlet or
      triplet), where the singlet-spin state reactivity gives a racemic mixture and the
      triplet reactivity gives an e.r. value >95 : 5.

PMID- 21180755
TI  - Ag nanosheet-assembled micro-hemispheres as effective SERS substrates.
AB  - Large-scale Ag nanosheet-assembled micro-hemispheres, with sufficient hot spots
      on their surfaces, have been achieved on an indium tin oxide substrate via
      electrodeposition. Surface-enhanced Raman scattering (SERS) measurements
      demonstrate that the Ag nanosheet-assembled micro-hemispheres can serve as
      sensitive and reproducible SERS substrates.

PMID- 21180756
TI  - Nitrogen-doped TiO2 thin films: photocatalytic applications for healthcare
      environments.
AB  - N-doped TiO(2) has for many years received interest as visible light
      photocatalytic materials. Here we give our perspective on the subject with
      special consideration towards the use of visible light photocatalysts in the
      field of antimicrobial materials with applications in healthcare environments.
      The subject is reviewed and critiqued from synthetic techniques to
      characterisation and assessment of functional properties. N-doped TiO(2) has huge
      potential to form commercially viable antimicrobial surfaces that are easily
      implemented within the healthcare environment. We aim to shed light on the
      illusive nature of the mechanism of the different types of N-doping and comment
      on how these affect the properties of the catalysts themselves. Small
      concentrations of nitrogen doped under mild conditions lead to interstitial
      doping, which also promotes the creation of oxygen vacancies. Many believe that
      it is these oxygen vacancies that actually promote the formation of visible light
      photocatalysis and hence there is an indirect correlation between the
      interstitial doping and the photocatalysis. As the concentration of interstitial
      nitrogen increases the oxygen vacancies increase, however the presence of oxygen
      vacancies in turn encourages substitutional doping which then fills the oxygen
      vacancies. This cyclic relationship leads to photocatalysts that are very
      sensitive to changing nitrogen concentration.

PMID- 21180757
TI  - Tristhienylphenylamine--extended dithiafulvene hybrids as bifunctional
      electroactive species.
AB  - Extended hybrid conjugated systems based on a trithienylphenylamine core with 1,
      2 and 3 peripheral dithiafulvenyl units have been synthesized and studied by
      cyclic voltammetry and UV-Vis. absorption spectroscopy. Theoretical calculations
      have also been undergone. The behaviour of these derivatives which depends on the
      number of dithiafulvene moieties grafted of the central core is cleared up. One
      polymer, obtained from derivative 3 presents polyelectrochromic properties.

PMID- 21180761
TI  - Porous structured SnSb/C nanocomposites for Li-ion battery anodes.
AB  - Here, we report a simple, cheap, and rapid synthesis method combined with
      physical and chemical routes for porous structured metal-based carbon
      nanocomposites, which can be applicable to anode materials for high performance
      Li-ion batteries.

PMID- 21180762
TI  - Effects of local electric fields on the redox free energy of single stranded DNA.
AB  - Influence of external electric field as well as base substitution effects on the
      reduction/oxidation free energies of single stranded DNA suggest that base
      sequencing via measuring redox properties might be feasible under the conditions
      that (i) a difference of ~ 230 kJ mol(-1) in the oxidation potentials is enough
      to discriminate between nucleobases conductance signals and (ii) the strand is
      long enough to reduce end effects.

PMID- 21180763
TI  - Chemical trend of Ln-M exchange couplings in heterometallic complexes with Ln =
      Gd, Tb, Dy, Ho, Er and M = Cu, V.
AB  - The 4f-3d exchange couplings were definitively and precisely determined in the
      dinuclear complexes (Ln-M) involving double MU-oxo-bridges, by means of combined
      high-frequency electron paramagnetic resonance and pulsed-field magnetization
      techniques, revealing a monotonic decrease of ferromagnetic J(Ln-Cu) in the order
      of the atomic number, (64)Gd to (68)Er.

PMID- 21180764
TI  - Optical chemical sensors based on hybrid organic-inorganic sol-gel nanoreactors.
AB  - Sol-gel porous materials with tailored or nanostructured cavities have been
      increasingly used as nanoreactors for the enhancement of reactions between
      entrapped chemical reactants. The domains of applications issued from these
      designs and engineering are extremely wide. This tutorial review will focus on
      one of these domains, in particular on optical chemical sensors, which are the
      subject of extensive research and development in environment, industry and
      health.

PMID- 21180765
TI  - Crystal structure of NdSi(6-z)Al(1+z)O(z)N(10-z) (z = 0.4) determined by single
      crystal X-ray diffraction.
AB  - Single crystals of JEM-phase NdSi(6-z)Al(1+z)O(z)N(10-z) were successfully
      prepared from starting powders of Si3N4, AlN and Nd2O3 at 1700  degrees C for 3 h
      under nitrogen atmosphere. The z value of Nd-doped JEM-phase was determined to be
      0.4 via determination of oxygen and nitrogen by elemental analysis. This result
      may be beneficial for overcoming the difficulty on preparation of single-phase
      JEM-phase Sialon materials and further characterization on their properties. The
      detailed crystal structure of Nd-Sialon was solved on the basis of single-crystal
      X-ray diffraction data for the first time. The space group is Pbcn (no. 60); a =
      9.3060(6) A, b = 9.7224(6) A, c = 8.8777(5) A; Z = 4; V = 803.22(8) A3; D(c) =
      3.971 g cm-3; R1 = 0.0297 and wR2 = 0.0739 for all reflections refined against
      F2, with GooF value of 1.031.

PMID- 21180766
TI  - RAF kinase inhibitory protein (RKIP) modulates cell cycle kinetics and motility.
AB  - RKIP-1 is a metastasis suppressor that is frequently downregulated in aggressive
      cancers. However, the consequences of RKIP loss in primary or immortalized cells
      have not yet been explored. Using HEK-293 RKIP depleted (termed HEK-499) and Flp
      In T-Rex-293 RKIP inducible cell lines combined with whole transcriptome
      analysis, we show that RKIP-1 silencing accelerates DNA synthesis and G1/S
      transition entry by inducing the expression of cdc6, MCM 2, 4, 6, 7, cdc45L,
      cyclin D2, cyclin E2, cyclin D1, SKP2 and the downregulation of p21(cip1).
      Moreover, RKIP depletion accelerates the time from nuclear envelop breakdown
      (NEB) to anaphase markedly, while the upregulation of RKIP shortened the NEB to
      anaphase time. We show that RKIP depletion induces the expression of NEK6, a
      molecule known to enhance G2/M transition, and down-regulates G2/M checkpoint
      molecules like Aurora B, cyclin G1 and sertuin that slow the G2/M transition
      time. These subtle changes in the kinetics of the cell cycle culminate in a
      higher proliferation rate of HEK-499 compared to control cells. Finally, we show
      that RKIP depletion enhances cellular motility by inducing the
      expression/stabilization of beta-catenin, vimentin, MET and PAK1. Overall, our
      data suggest that modulation of the cell cycle checkpoints and motility by RKIP
      may be fundamental to its metastasis suppressive function in cancer and that RKIP
      role in a cell is more intricate and diverse than previously thought.

PMID- 21180767
TI  - Identification of the gene cluster involved in muraymycin biosynthesis from
      Streptomyces sp. NRRL 30471.
AB  - Muraymycin, a potent translocase I inhibitor with clinical potential, is produced
      by Streptomyces sp. NRRL 30471. The structure of muraymycin is highly unusual and
      contains the hexahydro-2-imino-4-pyrimidylglycyl moiety (epicapreomycidine) and
      an ureido bond. Here we report the identification of the muraymycin gene cluster
      from Streptomyces sp. NRRL 30471. Sequencing analysis of a 43.4-kb contiguous
      region revealed 33 ORFs, 26 of which were proposed to be involved in muraymycin
      biosynthesis. Independent targeted inactivation of mur16 and mur17 directly
      abolished muraymycin production, demonstrating the role of the genes essential
      for muraymycin biosynthesis. These data provide insights into the molecular
      mechanisms for muraymycin biosynthesis, and lay a foundation for the generation
      of muraymycin derivatives with enhanced bioactivity via the strategies of
      combinatorial biosynthesis.

PMID- 21180768
TI  - Biocompatible dispersions of carbon nanotubes: a potential tool for intracellular
      transport of anticancer drugs.
AB  - The use of the biocompatible amphiphilic diblock copolymer poly(ethylene glycol-b
      propylene sulfide) (PEG44PPS20) allows a tuned loading of doxorubicin onto the
      surface of non-functionalized multi-walled carbon nanotubes and an efficient cell
      internalization. The obtained multi-walled carbon nanotube-based systems show
      enhanced cytotoxic activity with respect to non-vehicled doxorubicin.

PMID- 21180769
TI  - Thickness dependent self limiting 1-D tin oxide nanowire arrays by nanosecond
      pulsed laser irradiation.
AB  - Fast, sensitive and discriminating detection of hydrogen at room temperature is
      crucial for storage, transportation, and distribution of hydrogen as an energy
      source. One dimensional nanowires of SnO2 are potential candidates for improved
      H2 sensor performance. The single directional conducting continuous nanowires can
      decrease electrical noise, and their large active surface area could improve the
      response and recovery time of the sensor. In this work we discuss synthesis and
      characterization of nanowire arrays made using nanosecond ultraviolet wavelength
      (266 nm) laser interference processing of ultrathin SnO2 films on SiO2
      substrates. The laser energy was chosen to be above the melting point of the
      films. The results show that the final nanowire formation is dominated by
      preferential evaporation as compared to thermocapillary flow. The nanowire height
      (and hence wire aspect ratio) increased with increasing initial film thickness h0
      and with increasing laser energy density Eo. Furthermore, a self-limiting effect
      was observed where-in the wire formation ceased at a specific final remaining
      thickness of SnO2 that was almost independent of h0 for a given Eo. To understand
      these effects, finite element modeling of the nanoscale laser heating was
      performed. This showed that the temperature rise under laser heating was a strong
      non-monotonic function of film thickness. As a result, the preferential
      evaporation rate varies as wire formation occurs, eventually leading to a shut
      off of evaporation at a characteristic thickness. This results in the stoppage of
      wire formation. This combination of nanosecond pulsed laser experiments and
      thermal modeling shows that several unique synthesis approaches can be utilized
      to control the nanowire characteristics.

PMID- 21180770
TI  - Catalytic activity of gold supported on ZnO tetrapods for the preferential
      oxidation of carbon monoxide under hydrogen rich conditions.
AB  - It is reported that 3 nm gold nanoparticles deposited on ZnO tetrapods show high
      activity for the selective oxidation of carbon monoxide in hydrogen rich streams;
      the catalytic activity of this system is at least twice as high as the values
      hither to observed on any conventional support for this reaction.

PMID- 21180772
TI  - GPCR-2L: predicting G protein-coupled receptors and their types by hybridizing
      two different modes of pseudo amino acid compositions.
AB  - G protein-coupled receptors (GPCRs) are among the most frequent targets of
      therapeutic drugs. With the avalanche of newly generated protein sequences in the
      post genomic age, to expedite the process of drug discovery, it is highly
      desirable to develop an automated method to rapidly identify GPCRs and their
      types. A new predictor was developed by hybridizing two different modes of pseudo
      amino acid composition (PseAAC): the functional domain PseAAC and the low
      frequency Fourier spectrum PseAAC. The new predictor is called GPCR-2L, where
      "2L" means that it is a two-layer predictor: the 1st layer prediction engine is
      to identify a query protein as GPCR or not; if it is, the prediction will be
      automatically continued to further identify it as belonging to one of the
      following six types: (1) rhodopsin-like (Class A), (2) secretin-like (Class B),
      (3) metabotropic glutamate/pheromone (Class C), (4) fungal pheromone (Class D),
      (5) cAMP receptor (Class E), or (6) frizzled/smoothened family (Class F). The
      overall success rate of GPCR-2L in identifying proteins as GPCRs or non-GPCRs is
      over 97.2%, while identifying GPCRs among their six types is over 97.8%. Such
      high success rates were derived by the rigorous jackknife cross-validation on a
      stringent benchmark dataset, in which none of the included proteins had >=40%
      pairwise sequence identity to any other protein in a same subset. As a user
      friendly web-server, GPCR-2L is freely accessible to the public at
      http://icpr.jci.edu.cn/, by which one can obtain the 2-level results in about 20
      s for a query protein sequence of 500 amino acids. The longer the sequence is,
      the more time it may usually need. The high success rates reported here indicate
      that it is a quite effective approach to identify GPCRs and their types with the
      functional domain information and the low-frequency Fourier spectrum analysis. It
      is anticipated that GPCR-2L may become a useful tool for both basic research and
      drug development in the areas related to GPCRs.

PMID- 21180771
TI  - Proteolytic Activity Matrix Analysis (PrAMA) for simultaneous determination of
      multiple protease activities.
AB  - Matrix metalloproteinases (MMPs) and A Disintegrin and Metalloproteinases (ADAMs)
      are two related protease families that play key roles in matrix remodeling and
      growth factor ligand shedding. Directly ascertaining the proteolytic activities
      of particular MMPs and ADAMs in physiological environments in a non-invasive,
      real-time, multiplex manner remains a challenge. This work describes Proteolytic
      Activity Matrix Analysis (PrAMA), an integrated experimental measurement and
      mathematical analysis framework for simultaneously determining the activities of
      particular enzymes in complex mixtures of MMPs and ADAMs. The PrAMA method
      interprets dynamic signals from panels of moderately specific FRET-based
      polypeptide protease substrates to deduce a profile of specific MMP and ADAM
      proteolytic activities. Deconvolution of signals from complex mixtures of
      proteases is accomplished using prior data on individual MMP/ADAM cleavage
      signatures for the substrate panel measured with purified enzymes. We first
      validate PrAMA inference using a compendium of roughly 4000 measurements
      involving known mixtures of purified enzymes and substrates, and then demonstrate
      application to the live-cell response of wildtype, ADAM10-/-, and ADAM17-/-
      fibroblasts to phorbol ester and ionomycin stimulation. Results indicate PrAMA
      can distinguish closely related enzymes from each other with high accuracy, even
      in the presence of unknown background proteolytic activity. PrAMA offers a
      valuable tool for applications ranging from live-cell in vitro assays to high
      throughput inhibitor screening with complex enzyme mixtures. Moreover, our
      approach may extend to other families of proteases, such as caspases and
      cathepsins, that also can lack highly-specific substrates.

PMID- 21180773
TI  - A ratiometric fluorescent probe for oxalate based on alkyne-conjugated
      carboxamidoquinolines in aqueous solution and imaging in living cells.
AB  - A novel ratiometric fluorescent probe for oxalic acid was designed and
      synthesized, based on the zinc-containing [DAQZ@2Zn(2+)] complex. It shows highly
      selective "on-off" fluorescence changes with a more than 20 nm blue shift in
      wavelength for oxalic acids in aqueous solution. Moreover, it can fluorescently
      respond to oxalic acid in living cells.

PMID- 21180774
TI  - Lab-on-a-chip based immunosensor principles and technologies for the detection of
      cardiac biomarkers: a review.
AB  - This review examines the current state of the art lab-on-a-chip and microfluidic
      based biosensor technologies used in the detection of cardiac biomarkers. The
      determination and quantification of blood based, cardiac biomarkers are crucial
      in the triage and management of a range of cardiac related conditions, where time
      delay has a major impact on short and longer-term outcomes of a patient. The
      design and manufacturing of biomarker detection systems are multi-disciplinary in
      nature and require researchers to have knowledge of both life sciences and
      engineering for the full potential of this field to be realised. This review will
      therefore provide a comprehensive overview of chip based immunosensing technology
      as applied to cardiac biomarker detection, while discussing the potential
      suitability and limitations of each configuration for incorporation within a
      clinical diagnostics device suitable for point-of-care applications.

PMID- 21180775
TI  - Luminescent multifunctional lanthanides-based metal-organic frameworks.
AB  - Metal-organic frameworks based on trivalent lanthanides (LnMOFs) are a very
      promising class of materials for addressing the challenges in engineering of
      luminescent centres. Lanthanide-bearing phosphors find numerous applications in
      lighting, optical communications, photonics and biomedical devices. In this
      critical review we discuss the potential of LnMOFs as multifunctional systems,
      which combine light emission with properties such as microporosity, magnetism,
      chirality, molecule and ion sensing, catalysis and activity as multimodal imaging
      contrast agents. We argue that these materials present a unique chance of
      observing synergy between several of these properties, such as the coupling
      between photoluminescence and magnetism. Moreover, an integrated approach towards
      the design of efficient, stable, cheap, environmentally-friendly and
      multifunctional luminescent LnMOFs is still missing. Although research into
      LnMOFs is at its early stage and much basic knowledge is still needed, the field
      is ripe for new ideas, which will enable sensor devices and photonic prototypes
      to become a commercial reality (81 references).

PMID- 21180776
TI  - Structural diversity and magnetic properties in 1D and 2D azido-bridged
      cobalt(II) complexes with 1,2-bis(2-pyridyl)ethylene.
AB  - By utilizing a flexible co-ligand 1,2-bis(2-pyridyl)ethylene (2,2'-bpe), two new
      azido-bridged cobalt(II) complexes with the formulae [Co3(N3)6(OH2)2(2,2'
      bpe)2](n)(2,2'-bpe)(n) (1) and [Co(N3)2(2,2'-bpe)2](n) (2) have been synthesized
      and structurally characterized. Compound 1 shows an uncommon 1D chain comprised
      of double EO azido bridged five- and six-coordinated Co(II) geometries in a
      unique (-5-5-6-)(n) sequence of the coordination number. The 2,2'-bpe acts as a
      terminal co-ligand and an uncoordinated molecule in the crystal lattice. Moreover
      the adjacent 1D chain is assembled by C-Hpi interactions and the intermolecular
      hydrogen bonding between uncoordinated 2,2'-bpe and coordinated water molecules
      building a 2D layer. Whereas, compound 2 is a 2D coordination network containing
      the alternating double EO and double EE bridging modes of azides and ditopic 2,2'
      bpe bridges. The magnetic investigation of 1 reveals dominant intra-chain
      ferromagnetic interactions, with the double EO azide-bridge and weak inter-chain
      antiferromagnetic interactions, with overall metamagnetic behaviour, having
      magnetic ordering at 6 K. The magnetic behaviour of 2 shows spin-canted
      antiferromagnetism below a T(N) of 12 K.

PMID- 21180777
TI  - Synthesis and cytotoxicity of a bimetallic ruthenocene dicobalt-hexacarbonyl
      alkyne peptide bioconjugate.
AB  - Organometallic conjugates of receptor-targeting peptides are proposed as
      interesting candidates for novel cancer therapies since they are capable of
      targeting a specific kind of cell. Here, we have synthesised a dicobalt
      hexacarbonyl alkyne compound linked to the neurotensin peptide hormone. In order
      to circumvent synthetic difficulties encountered when adding a cobalt carbonyl
      moiety onto the hydrophilic alkyne peptide, and to enhance the cellular uptake we
      functionalised the alkyne neurotensin(8-13) fragment (NT) first N-terminally by
      ruthenocene carboxylic acid to form the metallocene-alkyne-NT conjugate 3, before
      adding Co2(CO)8 to a propargyl glycine residue to form the Co-alkyne derivative
      4. Compound 4 represents the first heterobimetallic organometallic peptide
      conjugate reported to date. It shows moderate cytotoxicity against HeLa, PT45 and
      HepG2 cell lines.

PMID- 21180778
TI  - Long-term home oxygen therapy in children and adolescents: analysis of clinical
      use and costs of a home care program.
AB  - OBJECTIVES: To describe the clinical and laboratory characteristics of patients
      on long-term home oxygen therapy followed up by the home care program of Hospital
      das Clinicas, School of Medicine, Universidade de Sao Paulo, during a period of 8
      years; to compare groups with and without secondary pulmonary hypertension; and
      to estimate the cost of the program using oxygen concentrators vs. oxygen
      cylinders provided by the hospital. METHODS: A descriptive, retrospective cohort
      study of patients on long-term home oxygen therapy followed up from 2002 to 2009
      at the Unit of Pulmonology, Children's Institute, Hospital das Clinicas, School
      of Medicine, Universidade de Sao Paulo. RESULTS: We studied 165 patients, of whom
      53% were male, with the following medians: age at the beginning of oxygen therapy
      -3.6 years; duration of oxygen therapy--7 years; and survival time after
      beginning of oxygen therapy--3.4 years. The main diagnoses were: cystic fibrosis
      (22%), bronchopulmonary dysplasia (19%), and bronchiolitis obliterans (15%). Of
      the 33 patients who underwent spirometry, 70% had severe obstructive lung
      disease. Echocardiogram was performed in 134 patients; 51% of them had secondary
      pulmonary hypertension. There was a statistically significant association between
      pulmonary hypertension and need of higher oxygen flows (chi-square, p = 0.011),
      and between pulmonary hypertension and longer duration of oxygen therapy
      (Logrank, p = 0.0001). There was no statistically significant difference between
      survival time after the beginning of oxygen therapy and pulmonary hypertension.
      The average monthly costs of the program were US$ 7,392.93 for concentrators and
      US$ 16,630.92 for cylinders. CONCLUSIONS: Long-term home oxygen therapy was used
      to treat different chronic diseases, predominantly in infants and preschool
      children. There was a high frequency of pulmonary hypertension associated with
      longer periods of oxygen use and greater oxygen flow, without association with
      survival rate. The use of concentrators instead of cylinders may reduce costs
      significantly.

PMID- 21180779
TI  - [Takayasu's disease with severe heart and arterial involvement in a preschool-age
      child].
AB  - The authors describe a case of Takayasu's arteritis in a child of only 3 years of
      age, emphasizing the rarity of this disease in this age group. The child was
      admitted to the emergency room in a post-convulsive state after a tonic-clonic
      seizure. After a detailed clinical examination, extensive diagnostic tests, and
      observation of the clinical evolution, the diagnosis was Takayasu's disease with
      severe cardiac and arterial involvement. The report warns pediatricians and
      cardiologists to awareness of the possibility of this disease in very small
      infants, in countries where it is underdiagnosed.

PMID- 21180780
TI  - [Critical analysis of criteria for the evaluation of low-molecular weight heparin
      biosimilars].

PMID- 21180781
TI  - [Digoxin: the results of the DIG study in the XXI century].
AB  - After the report that there was no statistical significance in the general
      mortality of the DIG study, the indication of digoxin in the treatment regimens
      for congestive heart failure (CHF) drastically decreased. Post hoc studies that
      reassessed the DIG study data, indicated that an aspect that was not considered
      in this multicenter study has a critical influence on the prognosis of patients:
      the serum levels of digoxin. Regarding those that received a placebo, the general
      mortality and hospitalization were decreased in patients with a digoxin level <
      0.9 ng/ml. At the first study that assessed the influence of digitalis in an
      experimental model of CHF, we verified in our lab that female rats with
      congestive syndrome secondary to myocardial infarction have a prolonged survival
      when undergoing treatment with digitoxin. The current information recommends that
      the merits of digoxin continue to be analyzed in order to adequately establish
      its importance in the treatment of CHF.

PMID- 21180782
TI  - [Case 6/2010 - 14 months female infant with double aortic isthmus coarctation].

PMID- 21180783
TI  - [Thrombolysis in massive pulmonary embolism based on the volumetric capnography].
AB  - This is the first report of a patient submitted to chemical thrombolysis due to
      massive pulmonary embolism (PE) during the postoperative period of neurosurgery,
      in whom due to the lack of adequate clinical conditions, no imaging assessment
      was performed. Clinical, gasometric and capnographic data allowed the decision to
      perform the thrombolysis with safety. The P(a-et)CO2 gradient decreased from 46.4
      mmHg to 11.8 mmHg (normal < 5 mmHg) and the end-tidal alveolar dead space
      fraction decreased from 0.85 to 0.37 (normal < 0.15) from the pre-thrombolysis
      period to the 7th day post-thrombolysis. We conclude that the volumetric
      capnography (VC) was useful in the patient's diagnosis and clinical follow-up.

PMID- 21180784
TI  - [Therapeutic inertia].

PMID- 21180785
TI  - [Cardiovascular responses to resistance exercise are affected by workload and
      intervals between sets].
AB  - BACKGROUND: the control of cardiovascular responses during resistance exercise
      (RE) is important for patient safety. OBJECTIVE: to investigate the influence of
      repetition maximum (RM) and rest interval between sets (RI) on heart rate (HR),
      systolic blood pressure (SBP) and rate-pressure product (RPP) during RE. METHODS:
      twenty healthy subjects (26 +/- 5 years of age) underwent RE protocols involving
      three sets of leg press (6 and 12 RM) and RI proportional to the contraction time
      (1:3 and 1:5). The HR was checked on a continuous basis by using a
      cardiotachometer and the SBP was checked at the end of the sets, via a protocol
      validated by the auscultatory method. RESULTS: the HR was influenced by the
      workload (p = 0.008) and sets (p < 0.001), but not by the RI (p = 0.087). The SBP
      suffered from the isolated effect of the number of sets (p < 0.001) and RI (p =
      0.017), but not from the workload (p = 0.95). The RPP rose in direct proportion
      to the workload (p = 0.036) and sets (p < 0.001), but in inverse proportion to
      the RI (p = 0.006). In 6 RM protocols, the variation in the HR was higher for RI
      = 1:3 (Delta = 11.2 +/- 1.1 bpm) than for RI = 1:5 (Delta = 4.5 +/- 0.2 bpm; p =
      0.002), but there was no difference for 12 RM (Delta 1:3 = 21.1 +/- 2.2 bpm;
      Delta 1:5 = 18.9 +/- 2.0 bpm, p = 0.83). The RI influenced the variation in SBP
      in all loads (6 RM - Delta 1:3 = 10.6 +/- 0.9 mmHg, Delta 1:5 = 6.6 +/- 0.7 mmHg;
      p = 0.02 and 12 RM - Delta 1:3 = 15.2 +/- 1.1 mmHg, Delta 1:5 = 8.4 +/- 0.7 mmHg;
      p = 0.04). The RPP rose in proportion to the workload (p = 0.036) and to the sets
      (p < 0.001), but in inverse proportion to the RI (p = 0.006). With RI = 1:3,
      there was difference in RPP for 6 RM (Delta = 2,892 +/- 189 mmHg.bpm) and 12 RM
      (Delta = 4,587 +/- 300 mmHg.bpm; p = 0.018), but not with RI = 1:5 (6 RM: Delta =
      1,224 +/- 141 mmHg.bpm, 12 RM: Delta = 2,332 +/- 194 mmHg.bpm; p = 0.58).
      CONCLUSION: regardless of the workload, an increased RI was associated with lower
      cardiovascular responses during RE, especially of SBP.

PMID- 21180786
TI  - [Severe aortic stenosis in asymptomatic patients: the dilemma of clinical versus
      surgical treatment].
AB  - Aortic valve stenosis has become increasingly prevalent, in agreement with the
      aging of the population. Thus, it has become increasingly common to treat
      asymptomatic patients with severe aortic stenosis. Although the patients with
      asymptomatic aortic stenosis belong to the same group, they are heterogeneous
      from a clinical, laboratory and echocardiographic point of view. The treatment of
      these patients raises the dilemma of the clinical versus the surgical treatment:
      should we submit the patient to the risks of surgery or keep the patient under
      clinical observation, running the risk of irreversible myocardial damage or even
      sudden death? Under this perspective and based on the current literature, this
      study supplies tools that help to stratify the patients. The valvular area,
      degree of calcification, transvalvular aortic flow velocity, left ventricular
      hypertrophy and stress test alterations are the factors that place asymptomatic
      individuals with severe aortic stenosis in a group called very-high risk, in
      which the surgical approach starts to be considered.

PMID- 21180787
TI  - [Myocardial scintigraphy at rest in chest pain].

PMID- 21180788
TI  - [Is ejection fraction the best parameter for the assessment of ventricular
      function?].

PMID- 21180789
TI  - [Concerns on generic enoxaparin use in acute coronary syndrome].

PMID- 21180791
TI  - Bone response to biosilicates with different crystal phases.
AB  - The aim of this study was to investigate the histological and histomorphometrical
      bone response to three Biosilicates with different crystal phases comparing them
      to Bioglass 45S5 implants used as control. Ceramic glass Biosilicate and Bioglass
      45S5 implants were bilaterally inserted in rabbit femurs and harvested after 8
      and 12 weeks. Histological examination did not revealed persistent inflammation
      or foreign body reaction at implantation sites. Bone and a layer of soft tissue
      were observed in close contact with the implant surfaces in the medullary canal.
      The connective tissue presented few elongated cells and collagen fibers located
      parallel to implant surface. Cortical portion after 8 weeks was the only area
      that demonstrated significant difference between all tested materials, with
      Biosilicate 1F and Biosilicate 2F presenting higher bone formation than Bioglass
      45S5 and Biosilicate vitreo (p=0.02). All other areas and periods were
      statistically non-significant (p>0.05). In conclusion, all tested materials were
      considered biocompatible, demonstrating surface bone formation and a satisfactory
      behavior at biological environment.

PMID- 21180792
TI  - Effect of an acid diet allied to sonic toothbrushing on root dentin permeability:
      an in vitro study.
AB  - This study quantified alterations in root dentin permeability after exposure to
      different acid beverages. Twenty-five third molars were sectioned below the
      cementoenamel junction, the root segment was collected, and the pulp tissue was
      removed. The root segments were connected to a hydraulic pressure apparatus to
      measure the permeability of root dentin after the following sequential steps,
      with 5 specimens in each: 1) phosphoric acid etching for 30 s (maximum
      permeability), 2) root planning to create new smear layer, 3) exposure to
      different acid substances for 5 min (orange, cola drink, vinegar, white wine,
      lemon juice), 4) toothbrushing with sonic toothbrush for 3 min, 5) toothbrushing
      with sonic toothbrush plus dentifrice for 3 min. Considering step I as 100%, the
      data were converted into percentage and each specimen was its own control. Data
      were analyzed statistically by Kruskal-Wallis and Dunn's post test at 5%
      significance level. All acidic substances increased dentin permeability
      significantly after scraping (p< 0.05). Toothbrushing after exposure to acid
      substances decreased dentin permeability and the association with dentifrice
      accentuated the decrease (p< 0.05), except for the specimens treated with cola
      drink. Thus, it may be concluded that all tested acid fruit juices increased
      dentin permeability, and toothbrushing with or without dentifrice can decrease
      root dentin permeability after dentin exposure to acid diet.

PMID- 21180793
TI  - Available fluoride in toothpastes used by Brazilian children.
AB  - Toothpastes should have a minimum concentration of 1000 ppm of fluoride (F) to
      control caries and also the active F agent must be chemically free (soluble) in
      the formulation. Thus, the aim of this study was to evaluate the concentration of
      soluble F in dentifrices used by 206 Brazilian children. The concentrations of
      total fluoride (TF), total soluble fluoride (TSF) and fluoride ion were
      determined. From these analyses, the concentrations of F as sodium
      monofluorophosphate (MFP) and % of insoluble F were calculated. F was analyzed
      with an ion specific electrode in duplicates. The majority of dentifrices used
      (96%) contained F and in 84% of them, TF concentration was according to that
      declared by the manufacturers. In the F-toothpastes, 78% showed TSF concentration
      >= 1000 ppm, varying from 422.3 to 1432.3 ppm F (mean +/- SD of 1017.6 +/-
      239.4). These findings suggest that most dentifrices used by Brazilian children
      present available fluoride concentration for caries control.

PMID- 21180794
TI  - Use of graduated syringes for measuring salivary flow rate: a pilot study.
AB  - The evaluation of the salivary flow rate is important in several situations of
      dental practice. However, weighing the collected salivary volume it is not a
      practical method in public health services. This work evaluated the use of
      hypodermic graduated syringes as a simpler alternative method to measure the
      salivary flow rate. Saliva samples were obtained from 50 individuals (31 females
      and 19 males) aged 8 to 32 years (mean age: 12.4 years), recruited at the
      outpatient dental clinics of two public health centers. After collection, the
      saliva was weighed in a graduated scale and the results compared with the volume
      obtained through its measurement, in mL, in graduated hypodermic syringes. There
      was a positive and significant relationship between the two methods of measuring
      salivary flow rates as demonstrated by the Pearson's correlation coefficient (r =
      0.996, with p<0.05). Measurement of the salivary flow rate using graduated
      syringes demonstrated to be a reliable method, with lower cost and more practical
      than the traditional method of salivary weighing.

PMID- 21180795
TI  - Effect of drying on the reproducibility of DIAGNOdent to detect caries-like
      lesions.
AB  - The aim of this study was to verify the drying effect on the reproducibility of
      DIAGNOdent (Dd) devices to detect caries-like lesions. Three areas were created
      in each of the 34 bovine incisors: sound (S), demineralized (DE) and
      remineralized (RE). One examiner measured each area with two Dd devices
      (denominated X and Y), twice under humid, and twice under dry condition. Intra
      rater agreement according each device and inter-device agreement were estimated
      by kappa statistics (k). Intra-rater agreement for device Y was substantial under
      humid (kappa (DE)=0.68 and kappa (RE+S)=0.68) and dry condition (k DE=0.64 and k
      RE+S=0.67). For device X, it was substantial under humid condition (k DE=0.57 and
      k RE+S=0.49), and it was almost perfect after air drying (kappa (DE)=1.0 and
      kappa (RE+S)=1.0). Inter-device agreement was slight (k =0.17) under humid
      condition, and it was substantial under dry condition (k =0.62). As
      reproducibility increased under dry condition, drying is advised to detect caries
      like lesions on free smooth surfaces when different devices are used.

PMID- 21180796
TI  - Evaluation of single root canals filled using the lateral compaction, tagger's
      hybrid, microseal and guttaflow techniques.
AB  - The aim of this study was to determine the percentage of voids, gutta-percha and
      root canal sealer using 4 different filling techniques. Fifty-two extracted
      maxillary lateral incisors were prepared using the crown-down pressureless
      technique. The teeth were randomly divided in 4 groups (n=13): Lateral compaction
      (LC), Tagger's hybrid (TH), MicroSeal (MS) and GuttaFlow (GF) techniques.
      Horizontal cross-sections were made at the 2, 10 and 15 mm levels from the apex.
      Digital images of the root canal areas were acquired using a stereomicroscope and
      examined using the Image Tool 3.0 software. Statistical analysis was performed
      using the Kruskal-Wallis test (alpha=0.05). In general, a significant decrease in
      the gutta-percha filled area and increase of sealer area were observed at the
      apical level for all the evaluated techniques (p<0.05). With regard to the
      presence of voids, no significant difference was found. MS and TH techniques
      showed a larger gutta-percha filled area than LC and GF techniques at the coronal
      and middle third level (p<0.05). From the results of the present study, it may be
      concluded that the gutta-percha filled area of fillings decrease at the apical
      level, regardless of the filling technique used.

PMID- 21180797
TI  - Sealing ability of MTA and amalgam in different root-end preparations and
      resection bevel angles: an in vitro evaluation using marginal dye leakage.
AB  - This in vitro study evaluated the effect of different apicoectomy angles,
      instruments used in root-end preparation, and dental materials used in
      retrofilling on apical sealing. Root ends were resected at 45 or 90 degrees in 80
      single-rooted teeth. For each type of apicoectomy, root-end cavities were
      prepared with either a round carbide #2 bur or an S12/90D ultrasonic tip. The
      root-end cavities in each subgroup (apicoectomy + root-end preparation) were
      filled with silver amalgam without zinc (Am) or with gray mineral trioxide
      aggregate -Angelus (MTA), and the specimens were immediately immersed in 0.2%
      rhodamine B for 24 h. Sealing was evaluated based on the dyed cross-sectional
      dentin area. Data were analyzed statistically by the Kruskal-Wallis test at 5%
      significance level. No group showed complete sealing of root-end areas. The only
      significant factor affecting microleakage was dental material, with MTA
      exhibiting less leakage.

PMID- 21180798
TI  - Fracture process characterization of fiber-reinforced dental composites evaluated
      by optical coherence tomography, SEM and optical microscopy.
AB  - This study used optical coherence tomography (OCT) compared to scanning electron
      microscopy (SEM) and optical microscopy (OM) to evaluate qualitatively crack
      propagation and final fracture in restorative composite materials - Filtek Z250
      and Filtek Z350 (3M ESPE) - with fiber reinforcement after cyclic loading.
      Samples were made using a split mold. Initially, 3-point bending tests were
      performed to determine the maximum force and tension at the fracture moment using
      samples without fiber reinforcement. Then, mechanical cycling tests were
      performed using samples with glass fiber embedded internally. The failures were
      analyzed using the 3 methods described before. OCT permitted good
      characterization of internal crack propagation of the dental composites, which,
      however, could not be visualized by either SEM or OM. OCT was proven to be
      laboratory research tool that is easy to use, does not require any specific
      preparation of the samples, and is less expensive than SEM.

PMID- 21180799
TI  - Comparison of isthmus detection methods in the apical third of mesial roots of
      maxillary and mandibular first molars: macroscopic observation versus operating
      microscope.
AB  - The aims of this study were to assess the presence and the frequency of isthmuses
      in the mesial roots of the maxillary and mandibular first molars (at two
      resection levels from the apex), and to compare the findings obtained by
      macroscopic observation (MO) and operating microscope (OM). Forty maxillary and
      40 mandibular mesial roots were observed at 3 and 5 mm from the apex initially
      macroscopically and then with the use of an OM. The presence of an isthmus and
      the number of root canals detected were recorded. Data were analyzed
      statistically by Fisher's exact test for isthmus evaluation and Wilcoxon signed
      rank-test for number of root canals at a confidence interval of 95%. Comparison
      between MO and OM regarding the number of roots with isthmuses provided the
      following results: Mandibular group: At 3 mm level: MO 19 ?s. OM 27; at 5 mm
      level: MO 31 ?s. OM 32. Maxillary group: At 3 mm level: MO 9 ?s. OM 14; at 5 mm
      level: MO 19 ?s. OM 21. Significant differences (p<0.05) were found concerning
      the accuracy of the isthmus detection methods at both resection levels (3 and 5
      mm) and both types of roots, as well as for the number of the canals inspected
      under the OM between the two resection levels of the mesial roots of the
      maxillary first molars. Under the tested conditions, OM increased the diagnostic
      accuracy of isthmus detection at both resection levels and root types.

PMID- 21180800
TI  - Sorption, solubility and residual monomers of a dental adhesive cured by
      different light-curing units.
AB  - The aim of this study was to assess polymerization ability of three light-curing
      units by evaluating the influence of the light source, curing regimen and
      permeant (water or ethanol) on sorption, solubility and amount of residual
      monomers of a dental adhesive. Specimens of Adper Single Bond 2 were fabricated
      using a stainless steel circular matrix (8 mm x 1 mm). One quartz-tungsten
      halogen (QTH) lamp and two light-emitting diode (LED) device at three different
      curing regimes (L1 = 12 J; L2 = 24 J; L3 = 24 J) were used to cure the specimens.
      Specimens were stored in two types of permeants - deionized water or 75% ethanol 
      for two storage times (G1 =7 days; G2 = 30 days). The specimens underwent water
      sorption and solubility tests, according to ISO 4049:2000 standard. After
      storage, residual monomers were identified and quantified by high performance
      liquid chromatography (HPLC). For sorption, L1 showed the highest values and QTH,
      the lowest. For solubility, in ethanol-stored groups, L1 had also the highest
      values, and QTH, the lowest, and findings were significantly different from the
      other curing regimens. L1 leached significantly more monomers than the others,
      and QTH had the lowest results. In conclusion, the type of light source, the
      curing regimen and the permeant affected sorption, solubility and amount of
      residual monomers of the adhesive under study.

PMID- 21180801
TI  - Effect of insertion method on knoop hardness of high viscous glass ionomer
      cements.
AB  - The aim of this study was to assess the Knoop hardness of three high viscous
      glass ionomer cements: G1 - Ketac Molar; G2 - Ketac Molar Easymix (3M ESPE) and
      G3 - Magic Glass ART (Vigodent). As a parallel goal, three different methods for
      insertion of Ketac Molar Easymix were tested: G4 - conventional spatula; G5 -
      commercial syringe (Centrix) and G6 - low-cost syringe. Ten specimens of each
      group were prepared and the Knoop hardness was determined 5 times on each
      specimen with a HM-124 hardness machine (25 g/30 s dwell time) after 24 h, 1 and
      2 weeks. During the entire test period, the specimens were stored in liquid
      paraffin at 37oC. Significant differences were found between G3 and G1/G2 (two
      way ANOVA and Tukey's post hoc test; p<0.01). There was no significant difference
      in the results among the multiple ways of insertion. The glass ionomer cement
      Magic Glass ART showed the lowest hardness, while the insertion technique had no
      significant influence on hardness.

PMID- 21180802
TI  - Enamel remineralization by fluoride-releasing materials: proposal of a pH-cycling
      model.
AB  - This study proposes a pH-cycling model for verifying the dose-response
      relationship in fluoride-releasing materials on remineralization in vitro. Sixty
      bovine enamel blocks were selected for the surface microhardness test (SMH1).
      Artificial caries lesions were induced and surface microhardness test (SMH2) was
      performed. Forty-eight specimens were prepared with Z 100, Fluroshield, Vitremer
      and Vitremer 1/4 diluted - powder/liquid, and subjected to a pH-cycling model to
      promote remineralization. After pH-cycling, final surface microhardness (SMH3)
      was assessed to calculate percent recovery of surface microhardness (%SMHR).
      Fluoride present in enamel (MUg F/mm3) and in the pH-cycling solutions (MUg F)
      was measured. Cross-sectional microhardness was used to calculate mineral content
      (?Z). There was no significant difference between Z 100 and control groups on
      analysis performed on - %SMHR, ?Z, MUg F and mg F/mm3 (p>0.05). Results showed a
      positive correlation between %SMHR and MUg F/mm3 (r=0.9770; p=0.004), %SMHR and
      MUg F (r=0.9939; p=0.0000001), ? and MUg F/mm3 (r=0.9853; p=0.0002), ? and MUg F
      (r=0.9975; p=0.0000001) and between MUg F/mm3 and MUg F (r=0.9819; p=0.001). The
      pH-cycling model proposed was able to verify in vitro dose-response relationship
      of fluoride-releasing materials on remineralization.

PMID- 21180804
TI  - Evaluation of the panoramic image formation in different anatomic positions.
AB  - The aim of this study was to determine size, shape and position of the image
      layer by evaluation of the radiographic image formation in different anatomic
      positions. A customized phantom was made of a rectangular acrylic plate measuring
      14 cm2 and 0.3 cm thick, with holes spaced 0.5 cm away and arranged in rows and
      columns. Each column was separately filled with 0.315 cm diameter metal spheres
      to acquire panoramic radiographs using the Orthopantomograph OP 100 unit. The
      customized phantom was placed on the mental support of the device, with its top
      surface kept parallel to the horizontal plane, and was radiographed at three
      different heights from the horizontal plane, i.e., the orbital, occlusal and
      mandibular symphysis levels. The images of the spheres were measured using a
      digital caliper to locate the image layer. The recorded data were analyzed
      statistically by the Student'-t test, ANOVA and Tukey' test (?=0.05). When the
      image size of spheres in horizontal and vertical axes were compared,
      statistically significant differences (p<0.05) were observed in all areas,
      portions of the image layer and heights of horizontal plane evaluated. In the
      middle portion of the image layer, differences in the image size of spheres were
      observed only along the horizontal axis (p<0.05), whereas no differences were
      observed along the vertical axis (p>0.05). The methodology used in this
      determined the precise size, shape and position of the image layer and
      differences in magnification were observed in both the horizontal and vertical
      axes.

PMID- 21180803
TI  - Effect of zoledronic acid used in the root surface treatment of late replanted
      teeth: a study in rats.
AB  - This study evaluated the use of zoledronic acid, a resorption inhibitor, as a
      medication for root resorption treatment of late replanted teeth. Twenty-four
      maxillary right central incisors of rats were avulsed and kept dry for 30 min.
      Then, the teeth were divided into 2 groups. In group I, root surface was treated
      with 2% sodium fluoride for 20 min; in group II, 10-6M zoledronic acid solution
      was used for 20 min. All root canals were filled with calcium hydroxide. Next,
      teeth were replanted in their respective sockets. After 15 and 60 days post
      replantation, the animals were killed and the anatomic pieces were obtained and
      prepared for microscopic and morphometric analyses. The results showed that
      zoledronic acid was capable of limiting the occurrence of root resorption and
      preserving cementum resorption. Further research must be performed to confirm the
      use of zoledronic acid in root surface treatment of late replanted teeth.

PMID- 21180805
TI  - A rare case of multiple talon cusps in three siblings.
AB  - Talon cusp is an uncommon anomaly, whose etiology may be disturbances in the
      morphodifferentiation stage. Dens in dente is also a rare anomaly that is
      challenging in clinic as it may cause pulp necrosis or periapical lesions due to
      the communication with the oral cavity. This article reports multiple talon cusps
      on permanent maxillary and mandibular incisors and molars in 3 siblings. A 9-year
      old boy presented with structures like nodules, shaped as cylindrical cones with
      a sharp point or a raindrop with deep developmental fissures on the palatal
      aspect of the maxillary central incisors, lingual aspect of the mandibular
      central incisors and labial aspect of both mandibular first molars. The buccal
      surface of the maxillary right central incisor was also affected. Some of them
      exhibited dens in dente. His 15-year-old sister had prominent talon cusps on the
      palatal surface of maxillary central incisors and buccal surface of the
      mandibular first molars and mandibular left second molar. His 7-year-old brother
      had only one trace talon on the maxillary left central incisor. No syndrome was
      identified in the patients. In conclusion, genetic inheritance may be a causative
      factor in talon cusp.

PMID- 21180806
TI  - Antinociceptive effect on mice of the hydroalcoholic fraction and (-) epicatechin
      obtained from Combretum leprosum Mart & Eich.
AB  - Previous studies on Combretum leprosum, a tree growing in the Northeastern states
      of Brazil, have shown antinociceptive effects of the ethanol extract of its
      leaves and bark, but studies examining its constituents are rare. The objective
      of this study was to evaluate the antinociceptive effect of the hydroalcoholic
      fraction (HF) of one of its constituents, the flavonoid (-) epicatechin (EPI),
      administered orally to mice (20-30 g) in models of chemical nociception, and the
      possible mechanisms involved. Different doses of HF (62.5 to 500 mg/kg) and EPI
      (12.5 to 50 mg/kg) were evaluated in models of abdominal writhing, glutamate,
      capsaicin, and formalin in animals pretreated with different antagonists:
      naloxone, ondansetron, yohimbine, ketanserin, pindolol, atropine, and caffeine in
      the abdominal writhing test. To determine the role of nitric oxide, the animals
      were pretreated with L-arginine (600 mg/kg, ip) in the glutamate test. The HF was
      effective (P < 0.05) in all protocols at different doses and EPI was effective in
      the abdominal writhing, capsaicin and glutamate tests (P < 0.05) at doses of 25
      and 50 mg/kg. However, in the formalin test it was only effective in the second
      phase at a dose of 25 mg/kg. The antinociceptive effect of HF was inhibited when
      HF was associated with yohimbine (0.15 mg/kg), ketanserine (0.03 mg/kg), and L
      arginine (600 mg/kg), but not with the other antagonists. HF and EPI were
      effective in models of chemical nociception, with the suggested participation of
      the adrenergic, serotonergic and nitrergic systems in the antinociceptive effect
      of HF.

PMID- 21180807
TI  - [Food and Nutrition in Public Health: constitution, contours and scientific
      status].
AB  - This paper aims to examine the route on which Food and Nutrition in Public Health
      was build in the Brazilian context, from its fields of origin, identifying
      tensions and convergences, seeking to demarcate its boundaries and to
      characterize its status within the scientific field. We seek to evince the
      existence of a movement marked by the fruitful encounter between the field of
      "Public Health" and a portion of the field of "Food and Nutrition", or more
      precisely, one of their cores, starring actors oriented by knowledge
      distinguished from other nuclei in this field. Such phenomena, that we postulate
      as outcomes of the contact nuclei of knowledge that identify the Public Health
      with the field of "Food and Nutrition", led to a specific core of distinct
      knowledge and praxis in this context corresponds to what we call "Food and
      Nutrition in Public Health". This is a process marked from the outset by tensions
      between the biological and social paradigms, becoming the one hand, as a major
      challenge to be faced, and secondly, as a promising way for the approach between
      different fields of science, both the more practical, such as those targeted to
      conceptual reflection.

PMID- 21180808
TI  - [(Inter)disciplinary spaces: Food/Nutrition/Health/Public Health].

PMID- 21180809
TI  - [Let us not forget what is singular and contingent...].

PMID- 21180810
TI  - [In defense of the epistemological pluralism].

PMID- 21180811
TI  - [A fertile field for Food and Nutrition in Public Health].

PMID- 21180813
TI  - [The field of Food and Nutrition from the perspective of comprehensive theories].
AB  - The present article is a brief reflection on the field of Food and Nutrition as
      it interconnects with the humanities. Relevant theorists' thinking as well as the
      experience of the authors were used as references. The main purpose is to
      stimulate the discussion on the food-and-nutrition issue, taking into account the
      complexities involved in the relations between food consumption and dietetics.
      Also it is expected to motivate nutritionists to reflect upon their professional
      practice. Incorporating the use of hermeneutics for the comprehension of the
      subject is justified in terms of its methodological significance. The importance
      of taking action in guiding food consumption through the association of the
      technical knowledge of the field with various perspectives of comprehensive
      theories is also discussed.

PMID- 21180814
TI  - [An overview of studies on nutrition and neglected diseases in Brazil].
AB  - The objective of this paper is to review the literature on the relationship
      between nutrition and neglected infectious disease in Brazilian populations, in
      particular Chagas' Disease, malaria, schistosomiasis and visceral leishmaniasis.
      The literature review was performed in January 2010 by searching the databases
      SciELO, LILACS and Medline. Two-hundred and ninety-three abstracts were
      retrieved, 66 of them were selected for full-text analysis and 43 were included
      in the review. This review reinforces the relevance of nutritional studies in
      public health for better understanding the aspects involved in the risk and
      prognosis of malaria, schistosomiasis, visceral leishmaniasis and Chagas'
      Disease. It was possible to detect an unbalance in the literature about the
      theme, with much more experimental studies than population-based studies.
      Although the first are essential for helping to understand the pathophysiological
      mechanisms underlying the association between nutritional deficits and those
      diseases, well designed population-based studies are fundamental for the
      translation of scientific research into effective actions for controlling
      neglected diseases.

PMID- 21180815
TI  - [The role of civil society in building the field of Food and Nutrition in Brazil:
      elements for reflection].
AB  - The inclusion of Food and Nutrition (FN) issues on the public agenda has gained
      progressive relevance in Brazil and the civil society (CS) has an important role
      in this process. This article examines how CS affects policies in this field
      based on a historical perspective of their influence in political arenas of the
      Federal Government. The analysis was based on the following questions: (1) the
      political and institutional participatory approaches; (2) the related issues and
      political demands; (3) the implications of this process in developing public
      policies. The research instruments have combined literature review and
      documentary analysis. It was concluded that the role of the civil society was
      crucial for the consolidation of the National Policy of FN and the National
      Policy of Food and Nutrition Security. The institutional engineering and the
      profile of social organizations were very different, ranging from social
      movements to policy networks. The topics on the agenda have changed over the
      period studied, with the strengthening of ethnic, racial and gender issues. The
      gains of this process depend on public sector capacity to regulate and support
      the functioning of these institutional arenas and to involve governmental
      segments that actually has decision making power.

PMID- 21180816
TI  - [National policies and the field of Food and Nutrition in Collective Health: the
      current scenario].
AB  - It is presented a review of the guidelines implementation of the National Food
      and Nutrition Policy (PNAN) contextualizing the actions in the Brazilian Unified
      Health System (SUS) scenario. At ten years of its publication, PNAN faces
      challenges both to expand and qualify the shares of food and nutrition on health.
      It is challenging to stand as interlocutor and legitimate representative of the
      area of health, political and institutional context of food security and
      nutrition. Issues related to the articulation of PNAN and future National Policy
      on Food and Nutrition Security will be analyzed to demonstrate the convergence of
      agendas among the priorities for the guarantee of the SAN. The authors identify
      the potential of this field of action, from the current institutional setting,
      and the need for comprehensive solutions that address the complexity of food and
      nutrition in health.

PMID- 21180817
TI  - [History of the scientific field of Food and Nutrition in Public Health in
      Brazil].
AB  - This paper aims to trace the history of the scientific field of Food and
      Nutrition in Public Health in Brazil (FNPH), trying to describe the contexts that
      allowed the construction, consolidation and redefinition of the field, to
      identify the Brazilian scientists who contributed to this process and address the
      scientific concepts or paradigms that guided the actions of these scientists. As
      methodological criteria of analysis three cross sections corresponding to
      contexts of history in this field were established: the first one covers the
      period from 1930 to 1963, the second one between 1964 and 1984 and the third one
      considers the period from 1985 to 2010. We conclude that the field of FNPH
      assumed the current configuration from the mid-1970's, within the so-called
      Brazilian health movement, whose main ideas were the achievement of health reform
      and the construction of the Unified Health System. We reaffirm the importance of
      multidisciplinary character and the premise of the important role of the field of
      FNPH in ensuring the human right to healthy food, a component of the set of
      conditions necessary for health promotion, disease prevention, surveillance and
      health recovery and improvement of quality of life for all Brazilians.

PMID- 21180818
TI  - [Culinary as an object of study and intervention in the field of Food and
      Nutrition].
AB  - Culinary is approached here as an object of food and nutritional studies and
      interventions aimed at dietary changes. In order to explore the culinary
      potential, two studies are presented: one qualitative, focusing on dietary
      intake, with subjects from two socioeconomic sectors submitted to salt
      restrictions; the other uses cooking as structural axis of an educational method
      for promoting healthy eating. In both studies one can observe the potential of
      culinary: in the first, as a medium which allows access to information about food
      procedures that can improve the quality of information about food intake and food
      practices and, in the second, as an effective space for interventions aimed at
      food habit changes by addressing their sensorial, cognitive, symbolic and
      procedural dimensions.

PMID- 21180819
TI  - [Food in the contemporary context: consumption, political action and
      sustainability].
AB  - The interdisciplinary field of reflections on food as politics goes through a
      process of expansion and overflow to the private sphere, and routine daily food
      consumption. This process seems to be a reflection of transformations in the
      global agrifood markets, the wide publicity and awareness of food hazards and the
      politicization of consumption. To the extent that individuals are to assume
      responsibility for the environmental and social consequences of their everyday
      choices, the specificity of political power in contemporary societies goes beyond
      the institutional level (food security and nutrition, social inequalities in
      access to food, agricultural policies and regulations advertising of food) to
      meet the private sphere. This paper shows, initially, some of the recent debates
      about the process of politicization of consumption and then explores a
      theoretical reflection on the ethical, political and ideological habits that
      relate to food consumption, including the locations and ways of acquiring and
      food preparation, the values of environmental preservation, solidarity with local
      producers and reflexive caution against food risks. Finally, points to a research
      agenda capable of capturing the processes of politicization of food and consumer
      practices in the field of political power.

PMID- 21180820
TI  - [Research on Food in Brazil: sustaining the autonomy of the Food and Nutrition
      field].
AB  - Based on Bourdieu's thoughts about the scientific fields, we visited the Research
      Groups Directory of the National Council for Scientific and Technological
      Development (CNPq), seeking to invest in critical and reflective approach on the
      segment of Brazilian research work concerned with "food". We identified a stable
      and growing set of research groups whose visibility is compromised, once its name
      is not included in the institutional taxonomies within the agencies that support
      research and researchers' formation. Its epistemological foundations, its
      theoretical and methodological bases are located in the sphere of Humanities and
      include a wide range of interacting disciplines, forming a significant complexity
      around its central object: food. The study of feeding phenomena calls for
      interdisciplinarity and makes the challenge of facing the tensions inherent to
      democratic life in which we have a glimpse in which the growing and collaborative
      coexistence among different epistemic references must take institutional place.

PMID- 21180821
TI  - [Risk behaviors for eating disorders among female adolescents from different
      social strata in the Brazilian Northeastern].
AB  - This study sought to estimate the prevalence of eating disorders (ED) and
      identify risk factors among female adolescents in Fortaleza, Ceara, Brazil. It
      was conducted a sectional study with 652 high school students (14-20 years) using
      the Bulimic Investigatory Test of Edinburgh (BITE). A logistic regression model
      was applied. Approximately one quarter of participants showed risk eating pattern
      and control weight practices, among 1.2% signs of an installed ED were found.
      Fear of weight gain was reported by 62% of adolescents, independently if studying
      at public or private schools (p>0.05), but the use of risk practices was higher
      among private schools students (p<0.05). Not having a religion (OR: 2.2, 95%CI:
      1.1-4.2) and studying in private school (OR: 1.7, 95%CI: 1.2-2.5) were associated
      with an increased risk of ED. The ED emerge as a public health problem even in
      the poor areas of Brazil and the desire for a thin body was not differentiated
      between different social strata, although the risk practices are significantly
      higher among respondents from private schools. Subjective and cultural aspects
      are presented not only as risk factors, but also as protectors.

PMID- 21180822
TI  - [Prevalence and determinants of obesity and overweight among reproductive age
      women living in the semi-arid region of Brazil].
AB  - The study estimated the prevalence and determinants of overweight and obesity in
      women of reproductive age in the Semi-Arid Region of Brazil. In the cluster
      sampling of 8,000 households of the state of Ceara, 6,845 women were surveyed.
      Overweight and obesity were measured by the body mass index and risk factors
      identified by multivariate analysis. The prevalences of overweight and obesity
      were 32.6% and 16.1%, respectively. After adjusted analysis, obesity was
      positively associated with age>30 years (PR=1.55), marital status, married
      (PR=1.36), elementary education (PR=1.40), age at menarche<12 years (OR=1.59),
      having >1 child (PR=1.65) and contraceptive use (PR=1.31). Specific health and
      nutritional conditions were identified as highly associated to morbid obesity:
      hypertension (PR=3.11), diabetes (PR=2.08), dissatisfaction with body image
      (PR=4.26) and procedures for weight loss (PR=2.73). The study concluded that
      overweight and obesity are highly prevalent in the Semi-Arid Region of Brazil.
      Education was the only socioeconomic determinant considered as amenable to
      change. The reproductive risk factors identified enforce the need to mobilize the
      services of prenatal and postpartum care and family planning to prevent and
      control obesity.

PMID- 21180823
TI  - [Symbolism on "natural" in food].
AB  - The incorporated senses represent a set of possibilities for future life able to
      build individual and collective identities. This work deepens the habitus, in
      Bourdieu's terms, associated with "natural" and fast-food styles, making an
      interpretative analysis of symbolic exchanges of elements reproduced in feeding
      practices. We believe that this bricolage arrangement of elements enables
      bartering and hybridism, marked by a tension that reflects the insecurity of
      technological innovations. The "natural" style represents an ideal of self
      sustainability, non-polluting production, which faces the sanitary and ecologic
      crisis of the planet, against the large-scale industrialization and fast
      urbanization, defined as depredation factors of basic living conditions. The
      exchanges happen in a symbolic game connected with the global economic game, in
      which social actors make bets, illusio, according to particular intentions in
      concrete action. There is a chance to reformulate the rules of the game in the
      "game", although with a precarious balance of forces, in which the weaker side
      loses, an agent may have the possibility of not reproducing the pressures of
      globalized feeding, which is far from what might seem supernatural.

PMID- 21180824
TI  - [Eating, nourishment and nutrition: instrumental analytic categories in the
      scientific research field].
AB  - Eating, nourishment or nutrition circulate in our culture as synonyms and thus do
      not account for the changes that occur in nourishment, which intended or
      unintended, have a hybridization pattern that represents a change of rules and
      food preferences. This paper aims to take these common sense conceptions as
      analytic categories for analyzing and interpreting research for the Humanities
      and Health Sciences in a theoretical perspective, through conceptualization. The
      food is associated with a natural function (biological), a concept in which
      nature is opposed to culture, and nourishment takes cultural meanings (symbolic),
      expressing the division of labor, wealth, and a historical and cultural creation
      through which one can study a society. One attributes to Nutrition a sense of
      rational action, derived from the constitution of this science in modernity,
      inserted in a historical process of scientific rationalization of eating and
      nourishing. We believe that through the practice of conceptualization in
      interdisciplinary research, which involves a shared space of knowledge, we can be
      less constrained by a unified theoretical model of learning and be freer to think
      about life issues.

PMID- 21180825
TI  - Nanotechnology and in situ remediation: a review of the benefits and potential
      risks.
AB  - In this review, we focus on environmental cleanup and provide a background and
      overview of current practice; research findings; societal issues; potential
      environment, health, and safety implications; and future directions for
      nanoremediation. We also discuss nanoscale zero-valent iron in detail. We
      searched the Web of Science for research studies and accessed recent publicly
      available reports from the U.S. Environmental Protection Agency and other
      agencies and organizations that addressed the applications and implications
      associated with nanoremediation techniques. We also conducted personal interviews
      with practitioners about specific site remediations. We aggregated information
      from 45 sites, a representative portion of the total projects under way, to show
      nanomaterials used, types of pollutants addressed, and organizations responsible
      for each site. Nanoremediation has the potential not only to reduce the overall
      costs of cleaning up large-scale contaminated sites but also to reduce cleanup
      time, eliminate the need for treatment and disposal of contaminated soil, and
      reduce some contaminant concentrations to near zero--all in situ.

PMID- 21180826
TI  - [Consumption to feed of resident adult population in rural area of the city of
      Ibatiba (ES, Brazil)].
AB  - It is a transverse study where a questionnaire of alimentary frequency was
      applied (QAF) in 150 adults resident of the rural area of the city of Ibatiba
      (ES, Brazil). QAF classified the alimentary consumption as: habitual (>4 times in
      the week), not habitual (<4 times in the week) and rarely (1 time a month), with
      objective of correlating the alimentary consumption with the chronic-degenerative
      diseases. The results evidenced a habitual consumption of rice, breads, stalk,
      bean, cow milk, animal fat, margarine, sugar and coffee, and a non habitual
      consumption of cake, potato, cookies, manioc, sweet potato, chayote, carrot,
      beet, pumpkin, juice of fruits, banana, orange, guava, mango and tangerine. It
      can be concluded that the feeding habit presented by the studied population it
      can come to increase in a medium or long period the prevalence and occurrences of
      chronic-degenerative diseases as hypertension, diabetes, obesity and coronary
      diseases. The alimentary consumption of this population needs concern, because
      when compared with the national patterns, it is observed some inadequacies, and
      it is known that this picture comes to every day causing damages the public
      health.

PMID- 21180827
TI  - [Conceptualizing and measuring food and nutrition security].
AB  - An interdisciplinary conceptual framework of food security is presented that
      identifies determinants at the macro-socioeconomic, regional-local, and household
      levels. Food insecurity is described as having consequences for health and well
      being that may or may not be expressed in the form of physical-biological
      consequences such as underweight or nutritional deficiencies. The implications of
      this perspective for measurement of food security are addressed. A comparative
      review of indicators commonly used to assess food security is presented, with
      special focus on the Brazilian Food Insecurity Scale, which was included in the
      2004 National Household Survey (PNAD). The history of the development of the
      scale in the U.S. and its validation in Brazil are described. Characterized as a
      direct measure of household food insecurity, this psychometric scale can be used
      together with indicators and measurement instruments from diverse fields to
      broaden understanding of this complex phenomenon.

PMID- 21180828
TI  - [Undergraduate education and health practices of speech and language pathologists
      working in public health services].
AB  - Comprehensive health care is still a challenge for all who participate in the
      transformation of undergraduate education and health care practices. Among health
      professionals, speech and language pathologists are also invited to reflect on
      these questions. The aim of this study was to investigate some aspects of the
      undergraduate education and health care practices of speech and language
      pathologists (graduates of the Federal University of Rio de Janeiro) working in
      public health units. A descriptive cross study was carried out with ten subjects
      who responded to a questionnaire and were interviewed. The transcribed data were
      analyzed based on their content and the frequency of the answers. The results
      showed that most of the interviewed professionals considered the traineeships as
      one of the most important experiences of the undergraduate course, had
      extracurricular experience in public health services, attended specialization
      courses, and worked in more than one public health unit. Also, the study found
      that individual therapy was the main activity carried out in the public health
      services by the professionals. The study identified relevant points to be
      discussed about undergraduate education and public health care practices for
      these health professionals.

PMID- 21180829
TI  - [Analysis of the progress of the oral health teams inserted in the Family Health
      Strategy in Pernambuco, Northeast Region, Brazil, 2002 until 2005].
AB  - The aim of this study was to analyze the implementation of oral health care in
      the Family Health Strategy in the State of Pernambuco, Brazil, 2002 until 2005.
      It was observed aspects regarding the expansion of the teams, the percentage of
      population covered and the rise in the quantitative of oral primary procedures.
      It was a descriptive and quantitative study, focusing on the 185 cities included
      in the Family Health Strategy and all cities that included an oral health care in
      the program. The results showed that the evaluation of the oral health teams was
      204.22%, while the percentage of the evolution of oral health care procedures
      19.19%. It was observed that the expansion of the type I (327,14%) was higher
      than type II (125,92%). The estimation of the population covered by oral health
      team was about 29.56% to 3.450 inhabitants (Decree n. 673/03). The financing of
      oral health care primary had an increase in the same period of 389.50%. At last,
      it was verified, in practice, the oral care existent service to oral primary care
      procedures were changed in oral health teams.

PMID- 21180831
TI  - [Disclosing the work processes of the community health agents on the Family
      Health Strategy in Vitoria (ES, Brazil)].
AB  - The community health agent (CHA) has a singular role as a "link" between the
      community and the health service. The main purpose of this
      descriptive/qualitative study is to evaluate the production of the CHA work
      processes in the Family Health Strategy in the county of Vitoria (ES, Brazil).
      The research was developed in the health region of Maruipe, a district in the
      county of Vitoria. The researchers invited 14 CHAs to use a half structured
      interview based on a guide script containing 24 questions. The process of work in
      health was considered as "a prevention and promotion of health", and the
      domiciliary visits were considered as being an everyday basic activity. The CHAs
      withhold several interpretations concerning to the work process and associated to
      the concept of unit the team has. It is also possible to notice a kind of
      idealism of the competences concerning to the CHA work, thus, causing a feeling
      of impotence and limitation when facing the challenges imposed by it. It is
      possible to conclude that the CHA needs tools and abilities that overcome their
      technical knowledge in order to act in a social scope and also to deal with the
      health needs of each user.

PMID- 21180830
TI  - [Pain and functionality in primary health care].
AB  - Musculoskeletal pain and functionality are linked to the individual health and,
      thus, influence the mode of interaction between individuals and between them and
      the environment that surrounds them. However, there are not many studies that
      question such health issues concerning the population in general, especially when
      we look at these issues from the basic care point of view. The aim of this
      article is to present initial data on the subject of pain and functionality in
      individuals with musculoskeletal complaints enrolled in a primary care unit and
      prompt a discussion on how complete the services provided by these units are.
      This study was carried out in a primary care unit and various households, among
      subjects aging 20 years or older. A functionality assessment tool and a Visual
      Analogue Scale were applied, and social and demographic issues were also
      considered. By using these tools, it was made an attempt to evaluate the profile
      of individuals in association with their degree of musculoskeletal pain and the
      degree of functionality in the activities of their daily lives, ages and
      occupations. We found a predominance of women in both groups: 84.37% and 81.25%,
      respectively. Nearly half of all people with musculoskeletal pain were
      housewives, and the average age between groups was over 55.

PMID- 21180832
TI  - [The dynamic binding of resources for health in Brazil: 1995 to 2004].
AB  - The aim of this study is to discuss the Brazilian Federal participation in the
      financing health sector from 1995 to 2004, having the basis the resources of the
      institutional initiatives related to the indexation of expenses, considering the
      macroeconomic adjustment practiced in that period and the institutions role to
      protect the cash flow. Examining the performances of the institutional mechanism
      actually adopted with the purpose of guarantee the flow regularity and extension
      of the values, by the analisys of the Temporary Contribution on the Financial
      Movement (TCFM) and the Constitutional Amendment Number 29 (CA 29) whose
      initiatives has their efficiency questioned. It demonstrates the impact of the
      destination of such measures from the statistics analysis of the use of the
      resources of the TCFM regarding its levies and the indexation of Union resources
      effects measures from the CA 29 before and after the application of its
      determinations.

PMID- 21180833
TI  - [Phenomenological extension of Heidegger's concepts of health and illness].
AB  - In the Zollikon seminars Heidegger gave an extraordinary contribution to the
      phenomenological study of health and disease. Throughout his life, this was the
      only chance the philosopher had to deal in depth with these questions. Disease
      was then determined as an ontological privation of health. Heidegger, however,
      did not develop an explicit concept of health. The author intends to develop to
      their full consequences some theses expounded in these seminars taking as
      reference two determinations then sketched: the essence of human health is
      identical with Dasein's unfolding essence in its opening to being; any disease is
      a "limitation of the possibility of living".

PMID- 21180834
TI  - [Evaluation of the cost of treating pressure ulcers in hospitalized patients
      using industrialized dressings].
AB  - This work evaluated wound dresses used in the Neurosurgery Department of
      Restauracao Hospital: polyurethane, hydrogel and activated carbon wound dresses
      and hydrogel with alginate used for pressure ulcer care. This work aimed to
      identify a critical factor that increases demand and cost of wound dresses. The
      evaluation conducted at the Neurosurgery Department identified individuals at
      risk of pressure ulcer development. Sixty-two patients were evaluated and the
      prevalence of pressure ulcer was 22.6% according to the Braden scale. Comparative
      evaluation between patients that didn't receive preventive measures and others
      that received, showed that the average daily cost of hospitalization for the
      first group was 45% higher than the mean for the second group. The Wilcoxon-Mann
      Withiney test compared the population at risk to develop pressure ulcer and
      population at low risk showing that the evaluation of Braden Scale scores between
      the groups presents statistically significant differences and confidence limits
      of 95%. Pressure ulcer is a key quality indicator in health services.It is
      possible to reduce costs and offer higher quality public health services by
      implementing a training program of nursing staff using a preventive measure
      protocol based on a test to evaluate risk as Braden Scale.

PMID- 21180835
TI  - [Evaluation of the capacity for governance of a State Health Department in
      monitoring and evaluation of basic health care provision--lessons learned].
AB  - The decentralization of the SUS requires state health departments to assume new
      powers as the monitoring and evaluation of Basic Care. This article aims to
      evaluate the "capacity for governance" of a State Health Northeastern Brazilian
      Department in monitoring and evaluation of Basic Care. From the technical
      cooperation held via component III of Proesf, key health care managers were
      interviewed, strategical documents were analyzed, and participatory observation
      of activities was carried out at a training centre, with a "contend analysis"
      procedure. Among the results, are: absence of "government project", problems of
      physical infrastructure, human resources and material, with low professional
      qualification in the use of information systems, monitoring and evaluation, and
      strategic planning, promoting and fragile bureaucratic work use of
      epidemiological data. In 2006, the Department used federal resources to
      strengthen the monitoring and evaluation of primary care by expanding its
      physical infrastructure, acquiring equipment and training for staff, without
      investing its own resource. To conclude, the Health Department has experienced
      difficulties in adjusting to decentralization, with the introduction of new
      working procedures into the institution.

PMID- 21180836
TI  - [The impasses of unconditional poverty: the experience of Collective Ombudsman in
      the Leopoldina region, Rio de Janeiro (RJ, Brazil)].
AB  - The experience of Collective Ombudsman developed in the Leopoldina region, city
      of Rio de Janeiro, enlarges the traditional vision of health vigilance and
      consists in organizing a system of qualitative evaluation of the sanitary
      vigilance able to identify the health problems of the population and the methods
      utilized in the attempt to overcome these problems. Health professionals,
      religious and community leaders congregated in monthly forums to present and
      discuss living conditions perceived in the communities in which they carry on
      their activities. From the point of view of the social dimensions involved in the
      health-illness processes, this work aims to discuss the way that poverty
      compromises the popular classes' health, especially for the mental health and the
      "diffuse suffering". The methodology allowed us to organize, in a systematic way,
      the listening and favored the recognition of local knowledge, constructed from
      the life experiences of the people who deal with the suffering, the illness and
      their determinants on the life conditions of the poor population. The precarious
      living conditions for a significant part of the population were perceived as
      generating impasses in the resolution of their health problems. The results point
      towards the importance of understanding the health problems of the population,
      the resources utilized to face them and proposals for possible solutions in the
      field of health.

PMID- 21180837
TI  - [The construction of care by the health team and the caretaker within a home-care
      program for bedridden patients in Porto Alegre (RS, Brazil)].
AB  - The main objective of this case study was to understand the construction of care
      in the Homecare Program for Bedridden Patients (PADA) of a basic health unit
      (UBS) in Porto Alegre, RS. Data were obtained from 13 caretaker groups in the
      UBS, and participating observation recorded in field diary in the patient's
      homes. An analysis of the discourse practices was performed inspired in
      Foucault's discourse concepts speeches and in studies on ethics and self-care. In
      the groups, the caretaker occupied a space that we metaphorically called the
      Delphic Oracle, a place for acceptance, listening and support. Hearing the
      dialogues that took place between the team and the caretakers made us face the
      contradiction present in the institutional discourse, which both stimulates self
      care, and imposes rules, duties, tasks. Care as a citizenship right opposite to
      care as submission and subjugation created tension inside the group several
      times. Foucault's notion of care comprises a synthesis of the exercise of a
      person over his- or herself, making him or her better as a human being and, at
      the same time, capacitating him or her to become a better citizen.

PMID- 21180838
TI  - [Representations and use intention of phytotherapy in primary health care].
AB  - The current observational study of investigative characteristics aimed to
      identify the representations and the use of phytotherapy on the primary health
      care and the factors related to the intention of use of this therapy. The
      population for this study was composed by 27 physicians from the Family Health
      Program in the city of Canoas, Rio Grande do Sul State, Brazil. This quality
      approach research was developed through a semi structured interviewing process
      embracing: conceptualization, experiences with phytotherapics and phytotherapy on
      primary health care. Such topics have brought up subcategories like attitudes,
      peers perception, control over prescription and intention of use of
      phytotherapics on primary care. The results have shown that the physicians do not
      have an institutional knowledge about the subject; a greater intention of use is
      related to the knowledge of the professionals on this therapeutic modality, based
      on the belief of its scientific evidence. In order to institutionalize
      phytotherapy in primary health care a more spread promotion of the studies on
      scientific evidences is necessary, as well as investments in improvements of
      professional skills. Thus, the general population will be able to benefit from
      phytotherapy as a more accessible alternative to health care.

PMID- 21180839
TI  - [Health education practices and Family Health Strategy].
AB  - This study evaluated health education, and particularly popular health education,
      as a methodological approach used in the Brazilian basic healthcare network and
      in the Family Health Strategy, a family health program of the Brazilian
      government. The literature on health education, educational practices in
      healthcare services, and popular health education was reviewed. We found that
      educational practices in healthcare services follow traditional methods and do
      not prioritize the establishment of links between healthcare workers and the
      population. To be consolidated as an educational practice, popular health
      education should be incorporated into the routine of health-care services. For
      this purpose, the preparation of healthcare workers should focus on actions to
      promote collective health and critical reflections on healthcare teaching and
      learning by all the individuals involved in these processes.

PMID- 21180840
TI  - [Risk assessment of genetically modified organisms].
AB  - Since the commercial approve in 1996, the global area of transgenic crops has
      raised more than 50 times. In the last two decades, governments have been
      planning strategies and protocols for safety assessment of food and feed
      genetically modified (GM). Evaluation of food safety should be taken on a case-by
      case analysis depending on the specific traits of the modified crops and the
      changes introduced by the genetic modification, using for this the concept of
      substantial equivalence. This work presents approaches for the risk assessment of
      GM food, as well as some problems related with the genetic construction or even
      with the expression of the inserted gene.

PMID- 21180841
TI  - [Popular participation in Ipatinga (MG, Brazil): achievements and challenges of
      the health sector].
AB  - Since the SUS implementation in the 90's, it has been possible to observe the
      change from a political, administrative, and financially centered system to a
      scene where thousands of agents started to constitute fundamental citizens in the
      field of health. The objective of this work is to understand how these different
      actors have absorbed and guaranteed the community the right to participate in the
      decision of public health policies. This research also tries to investigate the
      democratic speech and the participative practice implemented by the Worker's
      Party (PT) in the city of Ipatinga (MG, Brazil). This work uses as theoretical
      referential the Communicative Action Theory of Habermas and, from this theory, a
      model of democracy which is understood as the institutionalization of the
      discursive processes of opinion and will formation. The results obtained indicate
      that there is an important democratic history in the city, but with indications,
      however, of retrocessions in the participative practices of the health sector, as
      the reproduction of traditional practices of government is verified.

PMID- 21180842
TI  - [A case study of the Community Health Agents Program in Uruburetama, Ceara
      (Brazil)].
AB  - The program of community health agents institutionalized by the Department of
      Health in 1991 was the first strategy of its kind on national scale to bring
      attention to improving health in Brazil. In Ceara, this program exists since
      1986. The aim of this study is to identify and discuss the practices of health
      agents within the community. Interactions between a specific group of 19 infants
      in their first year of life from August 2004 to August 2005 and community health
      agents were followed and examined through individual interviews, focus groups,
      and field observations to gain a greater understanding of the common practices
      and the obstacles faced by these health agents. The study took place in
      Uruburetama, Ceara. Fifteen agents were the main source of information of this
      study. By looking at the analytical category of the health agent as an educator,
      it was empirically identified that they have an insufficient knowledge of the
      root causes and consequences of the social-economic determinants; and that the
      health practices themes and information are taken out of context of reality. This
      study points out the need to reinforce the training of health agents and, more
      importantly, strengthen their action as health educators in the community.

PMID- 21180845
TI  - Spatial distribution of mortality by homicide and social inequalities according
      to race/skin color in an intra-urban Brazilian space.
AB  - INTRODUCTION: In Brazil, deaths by external causes rank first in the mortality
      statistics. Nevertheless, studies which investigate the relationship between
      mortality by external causes and race/skin color are scarce. OBJECTIVES: To
      evaluate the relative contribution of race/skin color to the spatial distribution
      of mortality by homicide in Salvador, state of Bahia, Brazil, in the period 1998 
      2003. MATERIAL AND METHODS: This is a spatial aggregate study including
      secondary data on 5,250 subjects, using a unit of analysis called the "weighting
      area" (WA). Annual average death rates by homicide were estimated. The Global and
      Local Moran Index were used to evaluate the presence of spatial autocorrelation
      and the Conditional Auto Regressive (CAR) model was employed to evaluate the
      referred effect, using the R statistical package. RESULTS: Global and Local
      Moran's I tests were significant. CAR regression showed that the predicted
      mortality rate increases when there is a growth in the proportion of black males
      aged between 15 and 49 years. Geometrically weighted regression (GWR) showed a
      very small variation of the local coefficients for all predictors. CONCLUSION: We
      demonstrated that the interrelation between race, violence and space is a
      phenomenon which results from a long process of social inequality. Understanding
      these interactions requires interdisciplinary efforts that contribute to
      advancement of knowledge that leads to more specific Public Health interventions.

PMID- 21180846
TI  - [Death and its epidemiological investigation: considerations about some relevant
      aspects].
AB  - This article addresses death and issues related to its investigation, as
      important components for Epidemiology/Public Health. It highlights aspects linked
      to the improvement of quality of investigation and surveillance of death, as well
      as the advance of scientific/epidemiological research in this area, analyzed in
      view of current legislation and ethical principles in Brazil. We discuss the
      problem related to knowing "whom the health information belongs to and which are
      the limits of its utilization", considering also the possibility of using
      identified databases. At the end, we suggest competent ways, as a "Term of
      Responsibility/Confidentiality" signed by the researcher in order to enable
      scientific/epidemiological research to continue in the country, in a more
      opportune and agile manner.

PMID- 21180847
TI  - [Mapping of information on worker's health].
AB  - Geographic studies and spatial analyses have been recognized in Brazilian public
      health papers. It is still, however, very little explored by researchers. In a
      survey of the leading scientific journals covering issues related to Brazilian
      worker's health, we found the predominant use of charts and tables as a way to
      organize and present results with a small number of maps. This survey was
      conducted by examining all papers published in four journals, covering the period
      from 1967 to 2009 (Revista de Saude Publica, Cadernos de Saude Publica, Revista
      Saude e Sociedade, and Revista Brasileira de Epidemiologia). After analyzing the
      set of papers selected for the study, the papers that used maps were given
      special attention. The tools of geoprocessing and geostatistics with GIS support,
      although little used, open new possibilities to use thematic cartography in the
      field of workers' health. However, it is recommended that editors of scientific
      journals have detailed technical standards as well as specific reports for the
      publication of cartographic figures aimed at facilitating the modifications
      necessary for the improvement of the visual quality of maps and of the spatial
      correlations through cartography.

PMID- 21180848
TI  - [Profile of elderly admitted to public hospitals of Niteroi (RJ) due to falls].
AB  - OBJECTIVE: to describe the common characteristics of elderly people admitted to
      public hospitals of Niteroi (RJ) due to falls. METHODS: Cross-sectional study
      with 110 elderly patients (60 years and more) admitted to public hospitals in
      Niteroi - RJ, with fractures after falls. Data were collected by a
      multidimensional questionnaire. Multiple correspondence and cluster analysis were
      used to describe the characteristics of this population. RESULTS: The results
      indicated four groups. The first group was formed by individuals with better
      physical conditions who did not have a hip fracture, were more independent, used
      to go out more than twice a week, had good vision, had a short hospital stay, and
      were discharged to their homes. There was a group with worse conditions including
      those who were less independent, had a long hospital stay (more than 30 days),
      and died at the hospital. A third group was formed by those who had had a hip
      fracture, had poor vision, and used to go out less than once a week. The fourth
      group was comprised of those who stayed in the hospital from 11 to 30 days and
      used to go out once or twice a week. CONCLUSIONS: The multiple correspondence
      analysis proved to be a good technique to identify subgroups with common
      characteristics, which provides tools for the creation of strategies for fall
      prevention programs.

PMID- 21180849
TI  - [Comparison of simple and multiple imputation methods using a risk model for
      surgical mortality as example].
AB  - INTRODUCTION: It is common for studies in health to face problems with missing
      data. Through imputation, complete data sets are built artificially and can be
      analyzed by traditional statistical analysis. The objective of this paper is to
      compare three types of imputation based on real data. METHODS: The data used came
      from a study on the development of risk models for surgical mortality. The sample
      size was 450 patients. The imputation methods applied were: two single
      imputations and one multiple imputation and the assumption was MAR (Missing at
      Random). RESULTS: The variable with missing data was serum albumin with 27.1% of
      missing rate. The logistic models adjusted by simple imputation were similar, but
      differed from models obtained by multiple imputation in relation to the inclusion
      of variables. CONCLUSIONS: The results indicate that it is important to take into
      account the relationship of albumin to other variables observed, because
      different models were obtained in single and multiple imputations. Single
      imputation underestimates the variability generating narrower confidence
      intervals. It is important to consider the use of imputation methods when there
      is missing data, especially multiple imputation that takes into account the
      variability between imputations for estimates of the model.

PMID- 21180850
TI  - [Adjustment of evaluation criteria of adverse drug events for use in a public
      hospital in the State of Rio de Janeiro].
AB  - OBJECTIVES: To adapt the methodology, criteria and instruments for tracing
      adverse drug events proposed by the Institute for Healthcare Improvement and to
      evaluate the occurrence of adverse drug events in a specialized hospital.
      METHODS: The method selected for the identification of adverse drug events was an
      adjustment proposed by the Institute for Healthcare Improvement based on the
      retrospective review of medical charts conducted through explicit tracing
      criteria. The adjustment process for tracing criteria for adverse drug events was
      carried out by a panel of specialists based on the analysis of aspects related to
      validation, viability and relevance. This analysis was carried out from a sample
      of 112 patients. RESULTS: 21 tracing criteria for the detection of adverse drug
      events were selected. The incidence of adverse drug events in the analyzed
      hospital was 14.3%. In 25% of the cases there was a need for life-support
      intervention. CONCLUSION: Tracing criteria for adverse drug events enable
      monitoring events through time, allowing to evaluate if the strategies
      implemented in the medication system could show results for a better quality of
      care.

PMID- 21180851
TI  - [Prevalence of depressive symptoms and associated factors among southern
      Brazilian adults: cross-sectional population-based study].
AB  - To identify the prevalence of depressive symptoms and examine associated factors
      in a Southern Brazilian adult population, a cross-sectional population-based
      study was carried out, including 972 subjects, men and women, aged 20 to 69
      years, living in the urban area of Pelotas, Rio Grande do Sul. The sampling
      strategy relied on the census tracts of the city as primary sampling units and
      households as the secondary units. The questionnaire included socio-demographic,
      behavioral and nutritional variables. The prevalence of sadness, anxiety, loss of
      energy, lack of will to do things, thinking about the past, and wishing to stay
      at home were 29.4%, 57.6%, 37.4%, 40.4%, 33.8%, and 54.3%, respectively. Female
      gender, older ages, smokers and obese individuals showed association with
      depressive symptoms. Population-based studies using longitudinal designs may help
      to clarify the relationship between biopsychosocial variables and depressive
      symptoms.

PMID- 21180852
TI  - Prevalence of common mental disorders among the residents of urban areas in Feira
      de Santana, Bahia.
AB  - OBJECTIVE: To describe the prevalence of common mental disorders according to
      sociodemographic characteristics, lifestyle and medical conditions among
      residents of urban areas of Feira de Santana, Bahia. METHODS: A cross-sectional
      study was carried out, including a random sample of the urban population over the
      age of 15 years of Feira de Santana, Bahia, Brazil. We used a form to attain
      information on sociodemographic factors, lifestyle and disease frequency. The SRQ
      20 was used to measure common mental disorders (CMD). Statistical analysis
      adopted the p< 0.05 significance level; prevalence ratios and respective 95%
      confidence intervals were calculated. RESULTS: We studied 3,597 individuals,
      71.4% female. The global prevalence of CMD was 29.9%. Data analysis revealed that
      sociodemographic characteristics (sex, education, income), lifestyle and clinical
      conditions were associated with the prevalence of CMD. CONCLUSION: The study
      allowed us to estimate the prevalence of CMD among the urban population of a
      municipality located in Northeastern Brazil and to identify the characteristics
      associated with CMD prevalence that may interfere with mental health. In this
      sense, municipal healthcare policies should include actions aimed to encourage
      participation in leisure activities as well as campaigns to control smoking and
      chronic diseases.

PMID- 21180853
TI  - Prevalence of patients with respiratory symptoms through active case finding and
      diagnosis of pulmonary tuberculosis among prisoners and related predictors in a
      jail in the city of Carapicuiba, Brazil.
AB  - BACKGROUND: Prisons offer a fertile setting for the transmission of tuberculosis
      due to the presence of many classic risk factors for both infection and disease:
      overcrowding, poor ventilation, and little sunlight. Prisoners are often
      malnourished and have poor hygiene and are more likely to have a background of
      alcohol and drug abuse. OBJECTIVES: To determine the prevalence of prisoners with
      respiratory symptoms and pulmonary tuberculosis (PTB) through active case finding
      in a prisoner population of the county jail of Carapicuiba, and to study possible
      related variables. METHODS: This was a cross-sectional study, and respiratory
      symptomatic individuals (RSI) were detected through active case finding. Socio
      demographic data were collected from inmates' judicial history using a specific
      questionnaire. The RSI provided sputum specimens for detection of acid fast
      bacilli and culture for mycobacterium identification. RESULTS: Among the 397
      prisoners studied, 154 reported respiratory symptoms for more than three weeks,
      and were considered RSI; the variables associated with RSI were: having already
      been tried and incarcerated for more than six months and seven were diagnosed as
      PTB (1,763 cases/ 100,000 inhabitants). CONCLUSIONS: The prevalence of RSI and
      PTB cases were respectively 39 and 35 times greater than the general population.

PMID- 21180854
TI  - [Anemia, hypovitaminosis A and food insecurity in children of municipalities with
      Low Human Development Index in the Brazilian Northeast].
AB  - The objective of this study was to determine the prevalence of anemia and vitamin
      A deficiency and to analyze the association of food insecurity with hemoglobin
      levels and serum retinol in children under 5 years of age. This was a cross
      sectional study with 501 families from Gameleira and 458 families from Sao Joao
      do Tigre. Food insecurity was assessed according to the Brazilian Food Insecurity
      Scale. Hemoglobin and serum retinol levels were classified according to the WHO.
      Socioeconomic and environmental conditions and biological indicators of children
      were analyzed as hemoglobin and serum retinol determinants. The prevalence of
      anemia and vitamin A was higher in Gameleira compared to Sao Joao do Tigre.
      Moderate and severe food insecurity of families was 75% in Gameleira and 64% in
      Sao Joao do Tigre. Maternal education, per capita family income, not having a
      color TV, untreated water supply, type of flooring (dirt), and child age (< 2
      years) in Gameleira were associated with hemoglobin levels in the linear
      regression analysis. In Sao Joao do Tigre the association with hemoglobin levels
      was only for (no) motorcycle and child age. Variables per capita family income
      and sex in Gameleira and no mobile phone and lack of sanitation in Sao Joao do
      Tigre were statistically associated with serum retinol levels. The nutritional
      status of these populations is similar in terms of food insecurity but may
      present great differences in terms of the prevalence of specific nutritional
      deficits and their determinants.

PMID- 21180855
TI  - Influence of socioeconomic, behavioral and nutritional factors on dissatisfaction
      with body image among female university students in Florianopolis, SC.
AB  - This study aimed to estimate the prevalence of dissatisfaction with body image
      and associated socio-economic, behavioral and dietary factors in female
      university students from a public university in Florianopolis, SC. Body image was
      assessed by the Body Shape Questionnaire (BSQ-34) in a sample of 220 students.
      Nutritional status was investigated by body mass index (BMI), waist circumference
      (WC), and body fat percentage (%BF). Socio-economic characteristics (age, monthly
      household income, and parental schooling) as well as energy intake and going on
      restrictive diets were also investigated. Factors associated with dissatisfaction
      with body image were analyzed by multivariate Poisson regression analysis. The
      prevalence of dissatisfaction with body image was 47.3% (95% CI 40.7; 53.9).
      Nutritional status by BMI and going on a diet to lose weight were the variables
      associated with body dissatisfaction. Results showed a high prevalence of
      indicators of rejection of their physical fitness among university students,
      which signals toward the need for nutritional education actions at universities
      in order to clarify and prevent abnormal eating attitudes among students.

PMID- 21180856
TI  - Nutritional and clinical status, and dietary patterns of people living with
      HIV/AIDS in ambulatory care in Sao Paulo, Brazil.
AB  - INTRODUCTION: Nutrition currently plays a key role in the treatment of people
      living with HIV/AIDS (PLHA), especially in the case of metabolic alterations due
      to highly active antiretroviral therapy (HAART), which could be related to
      cardiovascular diseases (CD). OBJECTIVE: to describe the nutritional and clinical
      status, and the quality of diet of PLHA. METHODS: It is a cross-sectional study
      involving a network of ambulatory care facilities for PLHA in the city of Sao
      Paulo, Brazil. Patients, in use of HAART or not, were selected from December 2004
      to may 2006, through routine clinic visits. We collected: socio-demographic,
      clinical, biochemical, anthropometric measures and dietary data. Diet quality was
      evaluated according to a "protecting" or "non-protecting" pattern of consumption
      scores for CD. RESULTS: The sample had 238 patients on HAART and 76 without
      treatment. Mean serum levels of total cholesterol, triglycerides and glucose were
      higher in the HAART group (p < 0.001). The majority of patients of both the
      treated and untreated group were eutrophic with a mean body mass index (BMI) of
      24.4 (+/- 4.3) kg/m2 and 24.3 (+/- 3.5), respectively. The waist-hip ratio was
      higher among men on HAART (0.90 +/- 0.06 versus 0.87 +/- 0.05) (p < 0.001). The
      HAART group showed a mean food pattern score indicating a higher consumption of
      "non-protecting" foods for CD (p = 0.001). CONCLUSION: The results showed
      undesired nutritional and metabolic conditions among patients on HAART associated
      with CD. It is necessary to manage health intervention programs for PLHA in order
      to control cardiovascular risk factors before final outcomes.

PMID- 21180857
TI  - [Factors associated with insufficient physical activity: a population-based study
      in southern Brazil].
AB  - The aim of this study was to estimate the prevalence of insufficient physical
      activity and to find the factors associated to this outcome in Lages, Santa
      Catarina, Brazil (2007). A cross-sectional population-based study was carried out
      in a representative sample of individuals between 20 and 59 years of age
      (n=2,051). Physical activity was estimated using the short version of the
      International Physical Activity Questionnaire. Insufficient physical activity was
      defined as less than 150 minutes per week spent in moderate or vigorous physical
      activity. The prevalence of insufficient physical activity was 29.6% (95%CI:
      27.6; 31.7). The associated factors were to be male, obese, have high income, and
      negative self-perception of health status. The prevalence of insufficient
      physical activity was lower than reported by other Brazilian studies. Studies
      that distinguish different types of physical activity can contribute to a better
      understanding of the problem. The implementation of public policies that
      encourage the practice of regular exercises is required.

PMID- 21180858
TI  - [Sitting-time means and correlates in adults living in Ribeirao Preto-SP, Brazil,
      in 2006: OBEDIARP project].
AB  - This study aimed to estimate mean daily sitting-time and to identify correlates
      of sitting-time in adults living in the urban area of Ribeirao Preto-SP, in 2006.
      A cross-sectional population-based epidemiological study was carried out using
      three-stage cluster sampling. From a sample of 1,205 individuals, 930 attended
      the interviews. The variability introduced in the third sampling fraction was
      corrected by attributing sampling weights taking into account the non-response
      rate and the number of eligible units in each household, resulting in a weighted
      sample of 2,197 participants. To identify sitting time correlates, multiple
      linear regression models were used. The design effect was considered when
      calculating all estimates. The reported overall mean sitting-time/day was 280.9
      minutes. In the multivariate analysis, the following correlates were kept in the
      final model: gender; years of education; smoking; metabolic waste (Mets* . min* .
      week(-1)); working/day hours, and number of familial antecedents of obesity. The
      results pointed out sitting-time correlates and the need for health planning
      related to promotion and prevention policies.

PMID- 21180860
TI  - The COFFITO/BJPT partnership.

PMID- 21180859
TI  - [Association between malocclusion and dissatisfaction with dental and gingival
      appearance: study with Brazilian adolescents].
AB  - In spite of the high prevalence of malocclusion in adolescents reported
      worldwide, there are few studies that have investigated the association between
      normative malocclusion and self-rated dental and gingival appearance among
      adolescents. The aim of this study was to identify the association between
      normative malocclusion and dissatisfaction with dental and gingival appearance
      among Brazilian adolescents. A cross-sectional study was carried out with
      adolescents aged 15 to 19 years (n= 16,126) living in 250 towns of all five
      Brazilian regions. Dissatisfaction with dental and gingival appearance was the
      outcome. The main explanatory variable was malocclusion assessed by using the
      Dental Aesthetic Index - DAI. The other explanatory variables included were per
      capita family income, schooling delay, study conditions, sex, age, skin color,
      dental outcomes (untreated dental caries, missing teeth due dental caries, dental
      calculus, fluorosis, and dental pain) and use of dental services. Simple and
      multivariable Poisson regression analyses were performed. Dissatisfaction with
      dental appearance reached 11.4% (95%CI: 10.4-12.5) of the entire sample. All
      levels of malocclusion were associated with dissatisfaction with dental
      appearance. Adjusted multivariable analysis showed that dissatisfaction with
      dental appearance among individuals affected by severe or very severe
      malocclusion was respectively 40% and 80% higher than among those with normal
      occlusion. Malocclusion was associated with dissatisfaction with dental and
      gingival appearance. The results contribute to include self-rated dental
      appearance criteria in orthodontic treatment decision, mainly within the National
      Health System - SUS.

PMID- 21180861
TI  - The reality of open access and the search for financial stability.

PMID- 21180863
TI  - Heart rate responses during isometric exercises in patients undergoing a phase
      III cardiac rehabilitation program.
AB  - BACKGROUND: the magnitude of cardiovascular responses is dependent on the static
      and dynamic components as well as the duration and intensity of the contraction
      performed. OBJECTIVE: to evaluate the heart rate responses to different
      percentages of isometric contractions in 12 patients (63 +/- 11.6 years) with
      coronary artery disease and/or risk factors for coronary artery disease that were
      participating in a phase III cardiac rehabilitation program. METHODS: heart rate
      variation (DeltaHR) was evaluated during maximum (MVC, five and ten seconds in
      duration) and submaximal (SMVC, 30 and 60% of MVC-5, until muscle exhaustion)
      voluntary contraction, using a handgrip dynamometer. Additionally, the
      representative index of cardiac vagal modulation (RMSSD index) was calculated at
      rest (pre-contraction), at the final 30 seconds of SMVC and during recovery (post
      contraction). RESULTS: DeltaHR showed higher values in MVC-10 versus MVC-5 (17 +/
      5.5 vs 12 +/- 4.2 bpm, p<0.05) and the SMVC-60 vs SMVC-30 (19 +/- 5.8 vs 15 +/-
      5.1 bpm, p<0.05). However, results for CVM-10 showed similar DeltaHR compared to
      results for CVSM (p> 0.05). RICVM at rest decreased (p<0.05) during SMVC-30 (30%
      = 27.9 +/- 17.1 vs 12.9 +/- 8.5 ms) and SMVC-60 (60% =25.8 +/- 18.2 vs 9.96 +/-
      4.2 ms), but returned to the baseline values when the contraction was
      interrupted. CONCLUSIONS: in patients with coronary artery disease and/or risk
      factors for coronary heart disease, low intensity isometric contraction,
      maintained over long periods of time, presents the same effect on the responses
      of HR, compared to a high intensity or maximal isometric contraction of briefly
      duration.

PMID- 21180862
TI  - A systematic review about the effects of the vestibular rehabilitation in middle
      age and older adults.
AB  - OBJECTIVE: to summarize the results of clinical trials on vestibular
      rehabilitation (VR) in middle-aged and elderly people with vestibular disorders.
      METHODS: a search for relevant trials was performed in the databases LILACS,
      EMBASE, MEDLINE, SciELO, Cochrane, ISI Web of Knowledge and virtual libraries of
      theses and dissertations. Randomized controlled trials published in the last 10
      years and written in English, Portuguese or Spanish were included. The
      methodological quality of the studies was assessed by the PEDro scale. Results
      from the included studies were analyzed through a critical review of content.
      RESULTS: nine studies were included in the review. Four studies reported on
      participants aged over 40 years (middle-aged and elderly) and five studies
      consisted exclusively of elderly subjects (over 60 years). Findings of vestibular
      dysfunction were diverse and the most common complaints were body imbalance or
      postural instability (3 studies), and vertigo or dizziness (3 studies). The
      Visual Analogue Scale (VAS) was the most commonly used instrument to assess
      subjective perception of symptoms of vestibular dysfunction (4 studies).
      According to the PEDro scale, four studies were considered to be of good quality.
      The most common experimental intervention was the Cawthorne & Cooksey protocol (4
      studies). For most outcome measures, the studies comparing VR with another type
      of intervention showed no differences between the groups after the therapy.
      CONCLUSIONS: the studies included in this review provide evidence for the
      positive effects of VR in elderly and middle-aged adults with vestibular
      disturbances.

PMID- 21180864
TI  - Effects of physical exercise in the perception of life satisfaction and
      immunological function in HIV-infected patients: Non-randomized clinical trial.
AB  - BACKGROUND: there is a lack of research about the relationship between exercise
      and the psychological well-being of HIV-infected (Human Immunodeficiency Virus)
      patients. OBJECTIVE: the objective of this study was to investigate the influence
      of a physical training program on life satisfaction and on the immunological
      function in HIV-patients. METHODS: a total of 29 HIV-seropositive patients [age:
      45 +/- 2 yrs; Body Mass Index (BMI): 22.8 +/- 1.0 kg/m2 ; TCD4: 20.5 +/- 2.0%]
      were allocated to the control (CG, n=10) and to the experimental groups (EG,
      n=19). The EG participated in an exercise program combining aerobic, strength,
      and flexibility exercises for a period of 12 weeks [3 times/week of 30 min of
      aerobic exercise (workload corresponding to 150 bpm-PWC150); 50 min of strength
      exercises (3 sets of 12 repetitions in 5 exercises at 60-80% 12 RM); and 10 min
      of flexibility exercises (2 sets of 30 seconds at maximal range of motion of 8
      exercises)]. The immunological function was assessed by flow citometry [absolute
      and relative TCD4 cells counting] and the life satisfaction was assessed by the
      Life Satisfaction Index (LSI). RESULTS: the analysis of variance (ANOVA) showed
      no significant differences for relative and absolute CD4 T counts for both
      groups, however, a slight enhancement trend in the EG [16%, p=0.19] was observed.
      There was a significant improvement of LSI [approximately 15%; P<0.05] in EG, but
      not for CG. CONCLUSION: a physical activity program of moderate intensity
      improved life satisfaction perception in HIV-infected patients with no
      immunological function impairment.

PMID- 21180865
TI  - Pattern and rate of motor skill acquisition among preterm infants during the
      first four months corrected age.
AB  - OBJECTIVES: this study aimed to characterize the pattern and rate of motor skill
      acquisition among preterm infants from newborn to four months corrected age, in
      comparison with a group of full-term infants. METHODS: twelve healthy preterm
      infants (mean gestational age=33.6 weeks +/- 1.25) and 10 healthy full-term
      infants (mean gestational age=39.1 weeks +/- 0.73) participated in the study.
      These infants were assessed monthly (0-4 months of age) using the Test of Infant
      Motor Performance (TIMP). RESULTS: the motor performance pattern increased over
      the months in both groups, with variability in the total scores at all ages. The
      preterm group presented a higher mean score than shown by the full-term group
      between one and four months of age. In the full-term group, the motor acquisition
      rate was higher from age newborn to one month than from age three to four months.
      It was also found that the caregivers of the preterm infants began toy
      stimulation earlier than did the caregivers of the full-term infants. Both groups
      presented mean scores below the TIMP values. CONCLUSIONS: the preterm infants
      presented a pattern of motor development similar to the typical pattern regarding
      the sequence of abilities achieved. The preterm infants also presented a faster
      rate during the neonate period at one month of age. This suggests that correction
      for prematurity is unnecessary for preterm infants with these characteristics and
      that follow-up programs should instruct parents and caregivers to begin
      stimulation with toys at one month of age, thereby providing early exploration of
      various motor skills.

PMID- 21180866
TI  - Analysis of partial body weight support during treadmill and overground walking
      of children with cerebral palsy.
AB  - OBJECTIVE: to analyze the spatial-temporal characteristics and joint angles
      during overground walking without body weight support (BWS) and with 0% and 30%
      BWS, and during treadmill walking with the same BWS in children with cerebral
      palsy. METHODS: six children with hemiplegic and spastic cerebral palsy (7.70 +/-
      1.04 years old) were videotaped during overground walking at a comfortable speed
      with no BWS, with 0% and 30% BWS, and during treadmill walking with 0% and 30%
      BWS. Reflective markers were placed over main bony landmarks in both body sides
      to register the coordinates "x", "y", "z". RESULTS: during overground walking,
      children walked faster and presented longer and faster strides, longer duration
      of single-stance and swing periods, and shorter duration of double-stance period,
      than treadmill walking, regardless of BWS use. The hip was the only joint that
      presented a difference between body sides and experimental conditions; i.e. range
      of motion (ROM) was reduced in the plegic side when compared to the nonplegic
      side, and during overground walking without BWS when compared to 30% BWS.
      CONCLUSION: children with hemiplegic and spastic cerebral palsy were able to walk
      overground and on a treadmill with different percentages of BWS, and their
      performance was superior during overground walking, regardless of BWS use.

PMID- 21180867
TI  - Breathing pattern and thoracoabdominal motion in healthy individuals: influence
      of age and sex.
AB  - OBJECTIVE: to describe the breathing pattern and thoracoabdominal motion of
      healthy individuals, taking age and sex into consideration. METHODS: the study
      included 104 individuals aged 20 to 39, 40 to 59, and 60 to 80 years (41 males
      and 63 females), with normal body mass index and spirometric values. Participants
      were evaluated at rest in the supine position, by means of respiratory inductive
      plethysmography. The following variables were measured: tidal volume (Vt),
      respiratory frequency (f), minute ventilation (VE), inspiratory duty cycle
      (Ti/Ttot), mean inspiratory flow (Vt/Ti), rib cage motion (%RC), inspiratory
      phase relation (PhRIB), expiratory phase relation (PhREB), and phase angle
      (PhaseAng). Comparisons between the age groups were performed using one-way ANOVA
      or Kruskal-Wallis H, while comparisons between the sexes were performed using
      Student's t test or the Mann-Whitney U test, depending on the data distribution;
      p<0.05 was taken to be significant. RESULTS: comparison between the sexes showed
      that, in the age groups 20 to 39 and 60 to 80 years, women presented
      significantly lower values for Vt, VE, and Ti/Ttot than men, and there was no
      significant difference in the age group 40 to 59 years. Comparisons between the
      age groups showed that participants aged 60 to 80 presented significantly greater
      PhRIB and PhaseAng than participants aged 20 to 39 years, without significant
      differences in the breathing pattern. CONCLUSION: the data suggest that breathing
      pattern is influenced by sex whereas thoracoabdominal motion is influenced by
      age.

PMID- 21180868
TI  - Caracterization of adults with cerebral palsy.
AB  - BACKGROUND: cerebral Palsy (CP) is a group of permanent disorders of the
      development of movement and posture that cause functional limitation and are
      attributed to non-progressive disorders which occur in the fetal or infant brain.
      In recent years, with the increase in life expectancy of individuals with CP,
      several studies have described the impact of musculoskeletal disabilities and
      functional limitations over the life cycle. OBJECTIVE: to characterize adults
      with CP through sociodemographic information, classifications, general health,
      associated conditions, physical complications and locomotion. METHODS: twenty-two
      adults with CP recruited from local rehabilitation centers in an inner town of
      Brazil participated in this study. A questionnaire was used to collect data on
      sociodemographic characteristics, comorbities, and physical complications. A
      brief physical therapy evaluation was carried out, and the Gross Motor Function
      Classification System (GMFCS) and the Manual Ability Classification System (MACS)
      were applied. Data were analyzed through descriptive statistics. RESULTS: the
      mean age was 28.7 (SD 10.6) years, 86.4% of participants lived with parents, and
      4.5% were employed. Most of the sample consisted of spastic quadriplegic
      subjects, corresponding to levels IV and V of the GMFCS and MACS. Different
      comorbidities and important physical complications such as scoliosis and muscle
      contractures were present. More than half of the participants were unable to
      walk. CONCLUSIONS: Most participants demonstrated important restrictions in
      social participation and lower educational level. Adults with CP can be affected
      by several physical complications and progressive limitations in gait.

PMID- 21180869
TI  - Comparison between a national and a foreign manovacuometer for nasal inspiratory
      pressure measurement.
AB  - BACKGROUND: the measurement of nasal inspiratory pressure, known as the sniff
      test, was developed as a new test of inspiratory muscle strength, mainly used in
      neuromuscular conditions. The test is easy to be performed and noninvasive.
      Despite the clinical importance of assessment of nasal inspiratory pressure a
      national equipment is not available to assess it. OBJECTIVES: to compare a
      national with a foreign manovacuometer in assessing the nasal inspiratory
      pressure (sniff test) in healthy subjects. METHODS: 18 subjects were evaluated
      (age 21.44 +/- 2.8 years, BMI 23.4 +/- 2.5 kg/m2 , FVC 102.1 +/-1 0.3% pred, FEV1
      98.4 +/- 1% pred). We performed two measures of nasal inspiratory pressure using
      two different manovacuometer: a national and a foreign. All subjects performed
      the tests at the same time of day, in different days being the order of the
      testes established randomly. It was used the paired t test, Pearson correlation
      and the Bland-Altman plots for statistical analysis considering a 5% significance
      level. RESULTS: The averages observed for the two measures of nasal pressures
      were 125 +/- 42.4 cmH2O for the foreign equipment, and 131.7 +/- 2 8.7 cmH2O for
      the national equipment. The Pearson correlation showed significant correlation
      between the means with a coefficient of r=0.63. The t test showed no significant
      differences between both measurements (p>0,05). The BIAS +/- SD found in Bland
      Altman plot analysis was 7 cmH2O with limits of agreement between -57.5 cmH2O and
      71.5 cmH2O. CONCLUSION: the results suggest that the national electronic device
      is feasible and safe to the sniff test measurement in healthy subjects.

PMID- 21180870
TI  - Pain Locus of control scale: adaption and reliability for elderly.
AB  - BACKGROUND: pain is considered a multidimensional experience and is very common
      in the elderly. The pain locus of control has become essential to understand how
      the perceptions, expectations and beliefs are related to individual behavior,
      attitudes, coping and adherence of the elderly with regards to the health
      conditions and with the proposed treatment. Studies focused on adaptation and
      reliability of instruments are necessary for health professionals. OBJECTIVES:
      the present study performed the cross-cultural adaptation of the Pain Locus of
      Control Scale (C form of Multidimensional Health Locus of Control) for Brazil and
      assessed its intra and inter-examiner reliability among a sample of 68 elderly
      individuals with non-oncological pain living in the community. METHODS: the cross
      cultural adaptation of the scale was performed using the methodology standardized
      by Beaton et al. (2000)*. Pearson's correlation coefficient (PCC) and the
      intraclass correlation coefficient (ICC) were used for the statistical analysis
      (p<0.05). RESULTS: average age of the subjects was 69.6 +/- 5.5 years; most were
      women, with low levels of income and education. The average pain duration was
      10.2 years and the main clinical diagnosis was osteoarthritis. The reliability of
      the scale was adequate, with a regular to very strong correlations (PCC = 0.60 to
      0.93) and a moderate to nearly perfect ICC (0.60 to 0.93), in mainly the chance
      locus of control and medical and healthcare professionals locus of control
      subscales. CONCLUSION: an adequate reliability and applicability was observed in
      our sample after adjustments and adaptations of the scale for use in elderly

PMID- 21180871
TI  - [Diagnostic methods for cervical cancer screening].

PMID- 21180872
TI  - [Agreement between cytology, colposcopy and cervical histopathology].
AB  - PURPOSE: to evaluate the agreement between conventional cytology using the
      Papanicolaou test, repeated at the time of colposcopy, with colposcopic and
      histopathological findings. METHODS: the study was carried out at the central
      public health laboratory of the state of Pernambuco between January and July,
      2008, involving 397 women referred for colposcopic evaluation following an
      abnormal cervical smear test. Cytology was repeated at the time of colposcopy
      using conventional method, with particular attention being paid to the presence
      of abnormal colposcopic findings. The nomenclature used for cytology was the 2001
      Bethesda system terminology, while that used for histology was the World Health
      Organization 1994 classification. Cytology performed at the time of colposcopy
      was compared with colposcopy and with histopathology obtained by colposcopy
      directed biopsy. The Kappa coefficient was used to evaluate the agreement between
      methods, as well as the chi2 test, with the level of significance set at 5%.
      RESULTS: poor agreement was found between cytology performed at the time of
      colposcopy and colposcopic findings (K=0.33; 95%CI=0.21-0.45) and between
      colposcopy and histopathology (K=0.35; 95%CI=0.39-0.51). Cytology performed at
      the time of colposcopy compared with histopathology revealed a Kappa of 0.41
      (95%CI=0.29-0.530), which was considered to reflect moderate agreement.
      CONCLUSIONS: agreement was better between cytology and histopathology than
      between colposcopy and cytology or between colposcopy and histopathology.

PMID- 21180874
TI  - [Clinical and cytogenetic aspects of the Turner syndrome in the Brazilian Western
      region].
AB  - PURPOSE: to examine the association between cytogenetic characteristics and
      clinical and epidemiological changes in patients with Turner syndrome (TS).
      METHODS: Forty-two patients were included. Data were collected using a
      standardized questionnaire in interviews conducted with the responsible person
      and, when possible, with the patient. A detailed physical examination was
      performed. The association between karyotype, stigmata and clinical disorders
      were examined using the chi2 test. RESULTS: Sixty-four percent of TS patients
      were 45,X; 26,2% 45,X/46,X;7% 45,X/46Xi(Xq), and 2,3% 45,X/46,X,Del(Xq).
      Regardless of the karyotype, all patients had short stature. Low hair
      implantation was more frequent in patients with 45,X (p=0.03). Cardiovascular
      abnormalities (45%), otitis (43%), thyroid dysfunction (33%) and hypertension
      (26.6%) were the most frequent clinical disorders, but without correlation with
      the karyotype. Anthropometric measurements revealed a positive linear correlation
      of waist and hip circumference with age (r=0.9, p=0.01). Thirty-one patients
      (74%) were using or had previously used growth hormone (43%), sex steroids (30%),
      thyroxine (11.9%) or oxandrolone (9.5%). Comparison between gestational age at
      birth and learning difficulties showed a prevalence ratio of 1.71 (p>0.05).
      CONCLUSION: Low hair implantation is the most prevalent stigma in patients with a
      45,X karyotype and the most common clinical changes were cardiovascular problems,
      otitis, thyroid dysfunction and hypertension; however, they did not show any
      correlation with the karyotype.

PMID- 21180873
TI  - [Melatonin action in apoptosis and vascular endothelial growth factor in adrenal
      cortex of pinealectomized female rats].
AB  - PURPOSE: to evaluate the reactivity of VEGF-A and cleaved caspase-3 in the
      adrenal gland cortex of female pinealectomized rats treated with melatonin.
      METHODS: forty adult female rats were divided into 4 groups (G) of 10 animals: GI
      - no surgical intervention, with vehicle administration; GII - sham
      pinealectomized with vehicle administration; GIII - pinealectomized with vehicle
      administration; GIV - pinealectomized with melatonin administration (10
      ug/animal) during the night. After 60 days of treatment, all animals were
      anesthetized, and the adrenal glands were removed and fixed in 10% formaldehyde
      (phosphate buffered) for histological processing and paraffin embedding. Sections
      (5 um thick) were collected on silanized slides and submitted to
      imunnohistochemical methods for the detection of cleaved caspase-3 (apoptosis)
      and of vascular endothelial growth factor (VEGF-A) in the adrenal cortex. The
      data obtained were submitted to analysis of variance (ANOVA) complemented by the
      Tukey-Kramer test (p<=0.05). RESULTS: reactivity to cleaved Caspase-3 was noted
      in the zona glomerulosa of the adrenal glands in all studied groups. There were
      no significant differences in the zona glomerulosa; however, the zona fasciculata
      (15.51+/-3.12*, p<=0.05) and the zona reticularis (8.11+/-1.90*, p<=0.05)
      presented the smallest percentage of apoptosis in the pinealectomized group
      (GIII). The reactivity to the VEGF-A was stronger in the zona glomerulosa and
      weaker in the zona reticularis in all groups. We found a stronger VEGF-A
      reactivity in the zona fasciculata in the pinealectomized group (GIII).
      CONCLUSIONS: the pineal gland affects the arrangement of the zona glomerulosa and
      reticularis of the adrenal glands, which are related to the production of sex
      hormones.

PMID- 21180875
TI  - [Epidemiology and economic impact of cervical cancer in Roraima, a Northern state
      of Brazil: the public health system perspective].
AB  - PURPOSE: to evaluate the incidence and direct economic impact of cervical cancer
      (CC) in Roraima, in 2009, and to analyze the epidemiological profile of patients
      with this disease. METHODS: the histopathologic reports issued in Roraima in 2009
      were reviewed, as were hospital records of female patients under treatment for
      cancer. Clinical data and medical procedures related to CC were recorded. CC
      carriers were treated under expenses of the public Brazilian health system (SUS)
      in Roraima underwent an interview dealing with socio-economic topics. RESULTS: we
      registered 90 cases of CC and high grade pre-invasive lesions. Roraima has the
      highest incidence of CC of Brazil (46.21 cases/100,000 women), which is 3 times
      higher than that of breast cancer, comparable to low-income developing countries.
      The epidemiological profile shows patients with economic deprivation, social
      disadvantage, low education, early first intercourse (mean age is 13.8 years),
      and high parity (medium of 5.5 gestations). Among the patients included in this
      report, 71.7% had never been submited to a Pap smear, and ignorance about it was
      the main reported reason (47.4%). As a public health problem, the management of
      CC generates direct annual expenditures of more than R$ 600,000, with an average
      cost per patient of R$ 8,711. CONCLUSIONS: CC is the most common cancer among
      women from Roraima, and represents a serious public health problem in Roraima.
      Its high economic impact favors the implementation of preventive strategies from
      the standpoint of cost-effectiveness. The profile of patients reveals the
      ineffectiveness of preventive services in reaching patients with a socio-economic
      exclusion profile at high risk for cervical cancer.

PMID- 21180876
TI  - [Hysteroscopic evaluation in patients with infertility].
AB  - PURPOSE: to describe hysteroscopy findings in infertile patients. METHODS: this
      was a retrospective series of 953 patients with diagnosis of infertility
      evaluated by hysteroscopy. A total of 957 patients investigated for infertility
      were subjected to hysteroscopy, preferentially during the first phase of the
      menstrual cycle. When necessary, directed biopsies (under direct visualization
      during the exam) or guided biopsies were obtained using a Novak curette after
      defining the site to be biopsied during the hysteroscopic examination. Outcome
      frequencies were determined as percentages, and the chi2 test was used for the
      correlations. The statistical software EpiInfo 2000 (CDC) was used for data
      analysis. RESULTS: a normal uterine cavity was detected in 436 cases (45.8%).
      This was the most frequent diagnosis for women with primary infertility and for
      women with one or no abortion (p<0.05). Abnormal findings were obtained in 517 of
      953 cases (54.2%), including intrauterine synechiae in 185 patients (19.4%),
      endometrial polyps in 115 (12.1%), endocervical polyps in 66 (6.0%), submucosal
      myomas in 47 (4.9%), endometrial hyperplasia in 39 (4.1%), adenomyosis in five
      (0.5%), endometritis (with histopathological confirmation) in four (0.4%),
      endometrial bone metaplasia in two (0.4%), and cancer of the endometrium in one
      case (0.1%). Morphological and functional changes of the uterus were detected in
      5.6% of the cases, including uterine malformations in 32 (3.4%) and isthmus
      cervical incompetence in 21 (2.2%). CONCLUSIONS: intrauterine synechiae were the
      most frequent abnormal findings in patients evaluated for infertility. Patients
      with a history of abortion and infertility should be submitted to hysteroscopy in
      order to rule out intrauterine synechiae as a possible cause of infertility.

PMID- 21180877
TI  - [Maternal and perinatal outcomes in Bolivian pregnant women in the city of Sao
      Paulo: a cross-sectional case-control study].
AB  - PURPOSE: to evaluate the characteristics regarding care of Bolivian pregnant
      women and their outcomes in Hospital Municipal Vereador Jose Storopolli. METHODS:
      a cross-sectional retrospective case-control study comparing two groups of
      pregnant women from 2003 to 2007. The Study Group included 312 Bolivian pregnant
      women and the Control Group, 314 Brazilian women. The groups were compared with
      respect to demographic variables, the presence of maternal complications and
      perinatal outcomes. Statistical analysis was performed by chi2 test and, when
      necessary, by applying Yates' correction. RESULTS: compared to Brazilian mothers,
      a smaller number of Bolivian women received prenatal care (16.4 versus 5.1%,
      p<0.001) and among those that did, the percentage of those who had less than five
      visits was higher (50 versus 19.3%, p<0.001). Compared to the Brazilian group,
      the Bolivian group had fewer unwed mothers (12.1 versus 25.4%, p<0.001) and a
      lower number of nulliparous women (34.1 versus 43.6%, p=0.017). Congenital
      syphilis had a higher incidence in the Bolivian group (2.9 versus 0.5%, p<0.05),
      as well as a higher number of newborns classified as large for gestational age
      (14.6 versus 5.8%, p <0.001). CONCLUSIONS: the failure to attend prenatal care or
      its completion with an inadequate number of consultations, and the higher number
      of cases of congenital syphilis observed among the Bolivian women show the great
      vulnerability of this ethnic minority group to health problems. Consequently, it
      is necessary a strategic planning of the sectors responsible for coordinating
      assistance in our country, in order to reduce this disparity, either through
      socio-economic improvements or by the implementation of health care tailored to
      the needs of this group.

PMID- 21180878
TI  - [Maternal and perinatal outcomes in pregnancies complicated by sickle cell
      diseases].
AB  - PURPOSE: the aim of this study was to describe perinatal and maternal outcomes of
      pregnancies complicated by sickle cell disease (SCD), comparing to pregnancies of
      women with sickle cell trait (SCT). METHODS: this was a retrospective cohort
      study, covering the period from March 2001 to April 2008, which included all
      pregnant women with SCD (n=42) followed up at a university hospital in the
      Southeast region of Brazil. The maternal and perinatal outcomes were compared to
      those of pregnant women with SCT (n=56) who were followed up at the same service.
      RESULTS: SCD-SS was diagnosed in 42 (82.4%) pregnant women and SC in 9 (17.6%).
      Mean (+/-SD) maternal age was significantly lower in the SCD group (26.0 years)
      compared to SCT women (28.7+/-7.1 years; p=0.018). The following maternal
      complications were more common among women with SCD in comparison to SCT: urinary
      tract infection (25.5 versus 8.9%; p=0.04), pneumonia (23.5 versus 1.8%;
      p=0.002), pulmonary hypertension (15.7 versus 0%; p=0.002), and blood transfusion
      during delivery or postpartum (33.3 versus 5.4%; p=0.001). Adverse perinatal
      outcome was more frequent in the SCD group compared to the SCT group: prematurity
      (49 versus 25%, p=0.01); mean gestational age at delivery (35.2 versus 37.9
      weeks, p<0.001); fetal distress (56.9 versus 28.6%, p=0.006); birth weight <2,500
      g (62.7 versus 17.9%, p<0.001); mean birth weight (2,183 versus 2,923 g,
      p<0.001), and small for gestational age infants (29.4 versus 10.7%, p=0.029). Two
      maternal deaths (3.9%) occurred in the group with SCD. CONCLUSION: Pregnant women
      with SCD are at greater risk for maternal morbidity and for adverse perinatal
      outcomes than women with SCT.

PMID- 21180879
TI  - Transcriptional regulation of bidirectional gene pairs by 17-beta-estradiol in
      MCF-7 breast cancer cells.
AB  - Using cDNA microarray analysis, we previously identified a set of differentially
      expressed genes in primary breast tumors based on the status of estrogen and
      progesterone receptors. In the present study, we performed an integrated computer
      assisted and manual search of potential estrogen response element (ERE) binding
      sites in the promoter region of these genes to characterize their potential to be
      regulated by estrogen receptors (ER). Publicly available databases were used to
      annotate the position of these genes in the genome and to extract a 5'flanking
      region 2 kb upstream to 2 kb downstream of the transcription start site for
      transcription binding site analysis. The search for EREs and other binding sites
      was performed using several publicly available programs. Overall, approximately
      40% of the genes analyzed were potentially able to be regulated by estrogen via
      ER. In addition, 17% of these genes are located very close to other genes
      organized in a head-to-head orientation with less than 1.0 kb between their
      transcript units, sharing a bidirectional promoter, and could be classified as
      bidirectional gene pairs. Using quantitative real-time PCR, we further
      investigated the effects of 17beta-estradiol and antiestrogens on the expression
      of the bidirectional gene pairs in MCF-7 breast cancer cells. Our results showed
      that some of these gene pairs, such as TXNDC9/EIF5B, GALNS/TRAPPC2L, and
      SERINC1/PKIB, are modulated by 17beta-estradiol via ER in MCF-7 breast cancer
      cells. Here, we also characterize the promoter region of potential ER-regulated
      genes and provide new information on the transcriptional regulation of
      bidirectional gene pairs.

PMID- 21180880
TI  - Three-year follow-up study of respiratory and systemic manifestations of chronic
      obstructive pulmonary disease.
AB  - Few studies show patient outcomes over time in chronic obstructive pulmonary
      disease (COPD). In the present study, we monitored forced expiratory volume in
      the first second (FEV1) and other manifestations of the disease over 3 years in
      133 COPD patients (69% males, age = 65 +/- 9 years, FEV1 = 59 +/- 25%) evaluated
      at baseline. During follow-up, 15 patients (11%) died and 23 (17%) dropped out.
      Measurements for 95 (72%) COPD patients alive after 3 years were analyzed. FEV1,
      body mass index (BMI), 6-min walking distance (6MWD), Medical Research Council
      scale (MRC), Saint George's Respiratory Questionnaire (SGRQ), Charlson
      Comorbidity index, and BODE index were obtained at baseline and after 3 years. At
      baseline, 17 patients (18%) presented mild, 39% moderate, 19% severe, and 24%
      very severe COPD. Predicted FEV1 % and BMI did not change over the period (P >
      0.05). FEV1 in liters [1.25 (0.96-1.72) vs 1.26 (0.88-1.60) L; P < 0.001], 6MWD
      (438 +/- 86 vs 412 +/- 100 m; P < 0.001), MRC [1 (1-2) vs 2 (1-3); P = 0.002],
      Charlson index [3 (3-4) vs 4 (3-5); P = 0.009], BODE index (2.2 +/- 1.8 vs 2.6 +/
      2.3; P = 0.008), and total SGRQ (42 +/- 19 vs 44 +/- 19%; P = 0.041) worsened
      after 3 years compared to baseline measurements. These data show that COPD
      patients deteriorated during the 3-year follow-up despite the fact that they had
      only minor modifications in airway obstruction and body composition. They support
      the need for comprehensive patient assessment to better identify disease
      progression.

PMID- 21180881
TI  - Inactivation of capsaicin-sensitive nerves reduces pulmonary remodeling in guinea
      pigs with chronic allergic pulmonary inflammation.
AB  - Pulmonary remodeling is an important feature of asthma physiopathology that can
      contribute to irreversible changes in lung function. Although neurokinins
      influence lung inflammation, their exact role in the extracellular matrix (ECM)
      remodeling remains to be determined. Our objective was to investigate whether
      inactivation of capsaicin-sensitive nerves modulates pulmonary ECM remodeling in
      animals with chronic lung inflammation. After 14 days of capsaicin (50 mg/kg, sc)
      or vehicle administration, male Hartley guinea pigs weighing 250-300 g were
      submitted to seven inhalations of increasing doses of ovalbumin (1, 2.5, and 5
      mg/mL) or saline for 4 weeks. Seventy-two hours after the seventh inhalation,
      animals were anesthetized and mechanically ventilated and the lung mechanics and
      collagen and elastic fiber content in the airways, vessels and lung parenchyma
      were evaluated. Ovalbumin-exposed animals presented increasing collagen and
      elastic fiber content, respectively, in the airways (9.2 +/- 0.9; 13.8 +/- 1.2),
      vessels (19.8 +/- 0.8; 13.4 +/- 0.5) and lung parenchyma (9.2 +/- 0.9; 13.8 +/-
      1.2) compared to control (P < 0.05). Capsaicin treatment reduced collagen and
      elastic fibers, respectively, in airways (1.7 +/- 1.1; 7.9 +/- 1.5), vessels (2.8
      +/- 1.1; 4.4 +/- 1.1) and lung tissue (2.8 +/- 1.1; 4.4 +/- 1.1) of ovalbumin
      exposed animals (P < 0.05). These findings were positively correlated with lung
      mechanical responses to antigenic challenge (P < 0.05). In conclusion,
      inactivation of capsaicin-sensitive nerve fibers reduces pulmonary remodeling,
      particularly collagen and elastic fibers, which contributes to the attenuation of
      pulmonary functional parameters.

PMID- 21180882
TI  - Effects of 174 G/C polymorphism in the promoter region of the interleukin-6 gene
      on plasma IL-6 levels and muscle strength in elderly women.
AB  - We investigated the effect of -174 G/C single-nucleotide polymorphism in the
      promoter region of the IL6 gene on plasma IL-6 levels and muscle strength, and
      the relationship between IL-6 levels and muscle strength in elderly women. The
      sample consisted of 199 elderly residents (73.0 +/- 7.8 years old) from rest
      homes and the community in Belo Horizonte, MG, Brazil. -174 G/C polymorphism was
      determined by direct sequencing of the product by PCR, and plasma IL-6
      concentrations were measured by ELISA. Muscle strength in the knee joint was
      evaluated using a Biodex System 3 Pro(r) isokinetic dynamometer. ANCOVA was used
      to determine the effect of polymorphism on IL-6 levels and muscle strength, and
      the Pearson correlation coefficient to assess the relationship between IL-6
      levels and muscle strength. -174 G/C polymorphism was associated with the plasma
      IL-6 levels of elderly women (P < 0.01) since homozygotes for the G allele showed
      high IL-6 levels (GG 3.85 pg/mL, GC + CC 2.13 pg/mL). There was no association of
      polymorphism on muscle strength (P > 0.05). No association was found between IL-6
      levels and knee extensor muscle (r = 0.087, P = 0.306) or flexor (r = -0.011, P =
      0.894) strength. An interaction between -174 G/C polymorphism and housing
      conditions of the sample of elderly women was identified, with the effect of
      genotype on IL-6 levels being higher in the institutionalized elderly. These
      results support the evidence that -174 G/C polymorphism of the IL6 gene
      associates with individual variability of plasma IL-6 levels in elderly women.

PMID- 21180883
TI  - Manipulating Greek musical modes and tempo affects perceived musical emotion in
      musicians and nonmusicians.
AB  - The combined influence of tempo and mode on emotional responses to music was
      studied by crossing 7 changes in mode with 3 changes in tempo. Twenty-four
      musicians aged 19 to 25 years (12 males and 12 females) and 24 nonmusicians aged
      17 to 25 years (12 males and 12 females) were required to perform two tasks: 1)
      listening to different musical excerpts, and 2) associating an emotion to them
      such as happiness, serenity, fear, anger, or sadness. ANOVA showed that
      increasing the tempo strongly affected the arousal (F(2,116) = 268.62, mean
      square error (MSE) = 0.6676, P < 0.001) and, to a lesser extent, the valence of
      emotional responses (F(6,348) = 8.71, MSE = 0.6196, P < 0.001). Changes in modes
      modulated the affective valence of the perceived emotions (F(6,348) = 4.24, MSE =
      0.6764, P < 0.001). Some interactive effects were found between tempo and mode (F
      (1,58) = 115.6, MSE = 0.6428, P < 0.001), but, in most cases, the two parameters
      had additive effects. This finding demonstrates that small changes in the pitch
      structures of modes modulate the emotions associated with the pieces, confirming
      the cognitive foundation of emotional responses to music.

PMID- 21180884
TI  - Surfactant protein B gene polymorphism in preterm babies with respiratory
      distress syndrome.
AB  - The etiology of respiratory distress syndrome (RDS) is multifactorial and
      multigenic. Studies have suggested that polymorphisms and mutations in the
      surfactant protein B (SP-B) gene are associated with the pathogenesis of RDS. The
      objectives of this study were to determine and compare the frequencies of SP-B
      gene polymorphisms in preterm babies with and without RDS. We studied 151
      neonates: 79 preterm babies without RDS and 72 preterm newborns with RDS. The
      following four SP-B gene polymorphisms were analyzed: A/C at -18, C/T at 1580,
      A/G at 9306, and G/C at nucleotide 8714. The polymorphisms were detected by PCR
      amplification of genomic DNA and genotyping. The genotypes were determined using
      PCR-based converted restriction fragment length polymorphisms. The control group
      consisted of 42 (53%) girls and 37 (47%) boys. Weight ranged from 1170 to 3260 g
      and mean gestational age (GA) was 33.9 weeks (range: 29 to 35 weeks and 6 days).
      The RDS group consisted of 31 (43%) girls and 41 (57%) boys. Weight ranged from
      614 to 2410 g and mean GA was 32 weeks (range: 26 to 35 weeks). The logistic
      regression model showed that GA was the variable that most contributed to the
      occurrence of RDS. The AG genotype of the A/G polymorphism at position 9306 of
      the SP-B gene was a protective factor in this population (OR = 0.1681; 95%CI =
      0.0426-0.6629). We did not detect differences in the frequencies of the other
      polymorphisms between the two groups of newborns.

PMID- 21180885
TI  - Classification of brain tumor extracts by high resolution 1H MRS using partial
      least squares discriminant analysis.
AB  - High resolution proton nuclear magnetic resonance spectroscopy (1H MRS) can be
      used to detect biochemical changes in vitro caused by distinct pathologies. It
      can reveal distinct metabolic profiles of brain tumors although the accurate
      analysis and classification of different spectra remains a challenge. In this
      study, the pattern recognition method partial least squares discriminant analysis
      (PLS-DA) was used to classify 11.7 T 1H MRS spectra of brain tissue extracts from
      patients with brain tumors into four classes (high-grade neuroglial, low-grade
      neuroglial, non-neuroglial, and metastasis) and a group of control brain tissue.
      PLS-DA revealed 9 metabolites as the most important in group differentiation:
      gamma-aminobutyric acid, acetoacetate, alanine, creatine, glutamate/glutamine,
      glycine, myo-inositol, N-acetylaspartate, and choline compounds. Leave-one-out
      cross-validation showed that PLS-DA was efficient in group characterization. The
      metabolic patterns detected can be explained on the basis of previous multimodal
      studies of tumor metabolism and are consistent with neoplastic cell abnormalities
      possibly related to high turnover, resistance to apoptosis, osmotic stress and
      tumor tendency to use alternative energetic pathways such as glycolysis and
      ketogenesis.

PMID- 21180886
TI  - E3 ubiquitin ligase Cbl-b potentiates the apoptotic action of arsenic trioxide by
      inhibiting the PI3K/Akt pathway.
AB  - Arsenic trioxide (ATO) is a strong inducer of apoptosis in malignant
      hematological cells. Inducible phosphatidyl inositol 3 kinase (PI3K)-Akt
      activation promotes resistance to ATO. In the present study, we evaluated whether
      E3 ubiquitin ligase Cbl-b, a negative regulator of PI3K activation, is involved
      in the action of ATO. The effect of ATO on cell viability was measured by the
      Trypan blue exclusion assay or by the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. Apoptosis was determined by flow
      cytometry and protein expression was assayed by Western blotting. ATO decreased
      the viability of HL60 cells and induced cellular apoptosis, which was accompanied
      by transient activation of Akt. The PI3K/Akt inhibitor, LY294002, significantly
      increased ATO-induced apoptosis (P < 0.05). In addition, ATO up-regulated the
      expression of Cbl-b proteins. Furthermore, ATO inhibited cell viability with an
      IC50 of 18.54 MUM at 24 h in rat basophilic leukemia-2H3 cells. ATO induced
      cellular apoptosis with transient activation of Akt and Cbl-b was also up
      regulated. Rat basophilic leukemia-2H3 cells transfected with a dominant negative
      (DN) Cbl-b mutation showed overexpression of Cbl-b (DN) and enhanced Akt
      activation. Compared with cells transfected with vector, ATO-induced apoptosis
      was decreased and G2/M phase cells were increased at the same concentration (P <
      0.05). The PI3K/Akt inhibitor, LY294002, re-sensitized Cbl-b (DN) overexpressing
      cells to ATO and reversed G2/M arrest (P < 0.05). Taken together, these results
      suggest that Cbl-b potentiates the apoptotic action of ATO by inhibition of the
      PI3K/Akt pathway.

PMID- 21180887
TI  - Characterization of alpha thalassemic genotypes by multiplex ligation-dependent
      probe amplification in the Brazilian population.
AB  - Alpha-thalassemia is the most common inherited disorder of hemoglobin synthesis.
      Genomic deletions involving the alpha-globin gene cluster on chromosome 16p13.3
      are the most frequent molecular causes of the disease. Although common deletions
      can be detected by a single multiplex gap-PCR, the rare and novel deletions
      depend on more laborious techniques for their identification. The multiplex
      ligation-dependent probe amplification (MLPA) technique has recently been used
      for this purpose and was successfully used in the present study to detect the
      molecular alterations responsible for the alpha-thalassemic phenotypes in 8
      unrelated individuals (3 males and 5 females; age, 4 months to 30 years) in whom
      the molecular basis of the disease could not be determined by conventional
      methods. A total of 44 probe pairs were used for MLPA, covering approximately 800
      kb from the telomere to the MSLN gene in the 16p13.3 region. Eight deletions were
      detected. Four of these varied in size from 240 to 720 kb and affected a large
      region including the entire alpha-globin gene cluster and its upstream regulatory
      element (alpha-MRE), while the other four varied in size from 0.4 to 100 kb and
      were limited to a region containing this element. This study is the first in
      Brazil to use the MLPA method to determine the molecular basis of alpha
      thalassemia. The variety of rearrangements identified highlights the need to
      investigate all cases presenting microcytosis and hypochromia, but without iron
      deficiency or elevated hemoglobin A2 levels and suggests that these
      rearrangements may be more frequent in our population than previously estimated.

PMID- 21180888
TI  - Expression of TERT in precancerous gastric lesions compared to gastric cancer.
AB  - The objective of this study was to determine the levels of TERT mRNA and TERT
      protein expression in stomach precancerous lesions such as intestinal metaplasia
      (IM) and gastric ulcer (GU) and compare them to gastric cancer (GC). Real-time
      PCR was performed to detect TERT mRNA expression levels in 35 biopsies of IM, 30
      of GU, and 22 of GC and their respective normal mucosas. TERT protein was
      detected by immunohistochemistry in 68 samples, 34 of IM, 23 of GU, and 11 of GC.
      Increased TERT mRNA expression levels were observed in a significant number of
      cases, i.e., 46% of IM, 50% of GU, and 79% of GC. The relative mean level of TERT
      mRNA after normalization with the beta-actin reference gene and comparison with
      the respective adjacent normal mucosa was slightly increased in the IM and GU
      groups, 2.008 +/- 2.605 and 2.730 +/- 4.120, respectively, but high TERT mRNA
      expression was observed in the GC group (17.271 +/- 33.852). However, there were
      no statistically significant differences between the three groups. TERT protein
      positive immunostaining was observed in 38% of IM, 39% of GU, and 55% of GC. No
      association of TERT mRNA and protein expression with Helicobacter pylori
      infection or other clinicopathological variables was demonstrable, except for the
      incomplete type vs the complete type of IM. This study confirms previous data of
      the high expression of both TERT mRNA and protein in gastric cancer and also
      demonstrates this type of changed expression in IM and GU, thus suggesting that
      TERT expression may be deregulated in precursor lesions that participate in the
      early stages of gastric carcinogenesis.

PMID- 21180889
TI  - Enhanced inhibition of murine prostatic carcinoma growth by immunization with or
      administration of viable human umbilical vein endothelial cells and CRM197.
AB  - Vaccination with xenogeneic and syngeneic endothelial cells is effective for
      inhibiting tumor growth. Nontoxic diphtheria toxin (CRM197), as an immunogen or
      as a specific inhibitor of heparin-binding EGF-like growth factor, has shown
      promising antitumor activity. Therefore, immunization with or administration of
      viable human umbilical vein endothelial cells (HUVECs) combined with CRM197 could
      have an enhanced antitumor effect. Six-week-old C57BL/6J male mice were
      vaccinated with viable HUVECs, 1 x 10(6) viable HUVECs combined with 100 MUg
      CRM197, or 100 MUg CRM197 alone by ip injections once a week for 4 consecutive
      weeks. RM-1 cells (5 x 10(5)) were inoculated by sc injection as a preventive
      procedure. During the therapeutic procedure, 6-week-old male C57BL/6J mice were
      challenged with 1 x 10(5) RM-1 cells, then injected sc with 1 x 10(6) viable
      HUVECs, 1 x 10(6) viable HUVECs + 100 MUg CRM197, and 100 MUg CRM197 alone twice
      a week for 4 consecutive weeks. Tumor volume and life span were monitored. We
      also investigated the effects of immunization with HUVECs on the aortic arch wall
      and on wound healing. Vaccination with or administration of viable HUVECs+CRM197
      enhanced the inhibition of RM-1 prostatic carcinoma by 24 and 29%, respectively,
      and prolonged the life span for 3 and 4 days, respectively, compared with those
      of only vaccination or administration with viable HUVECs of tumor-bearing
      C57BL/6J mice. Furthermore, HUVEC immunization caused some damage to the aortic
      arch wall but did not have remarkable effects on the rate of wound healing; the
      wounds healed in approximately 13 days. Treatment with CRM197 in combination with
      viable HUVECs resulted in a marked enhancement of the antitumor effect in the
      preventive or therapeutic treatment for prostatic carcinoma in vivo, suggesting a
      novel combination for anti-cancer therapy.

PMID- 21180890
TI  - Cardiovascular risks in adolescents with different degrees of obesity.
AB  - BACKGROUND: There have been few studies on cardiovascular risk factors in
      adolescents with different degrees of obesity. OBJECTIVE: To evaluate metabolic
      effects associated with different degrees of obesity in adolescents and their
      impact on cardiovascular risks. METHODS: Cross-sectional study of 80 obese
      adolescents, divided in two groups: 2<z-BMI<2.5 and z-BMI >2.5, classified as
      obese with lower or higher degree of obesity, respectively. Physical examination
      was carried out, as well as biochemical and body composition assessment. The
      statistical analysis was performed with t-Student and Chi-square tests, aiming at
      comparing both groups. A multiple logistic model was used to verify the
      associations between the biochemical variables and the degree of obesity. Risk
      scores were developed for cardiovascular disease, according to the number of
      alterations found in the following variables: fasting glycemia, triglycerides,
      HDL and blood pressure. Association between these scores and degree of obesity
      were verified. RESULTS: The two groups differed regarding weight, waist
      circumference, fasting glycemia and insulin, HOMA-IR, triglycerides, HDL, blood
      pressure (BP) and body composition measurements (p<0.05). The adolescents with
      the higher degree of obesity presented higher frequencies of alterations for
      glycemia, HOMA-IR, triglycerides, HDL and BP (p<0.05). The logistic model showed
      associations between the degree of obesity and the variables: HDL (OR=5.43), BP
      (OR=4.29), TG (OR=3.12). The risk score demonstrated that 57.7% of the
      adolescents with higher degrees of obesity had two or more metabolic alterations
      versus 16.7% from the other group (p<0.001). CONCLUSION: The degree of obesity
      influenced the onset of alterations that comprise the metabolic syndrome,
      increasing the cardiovascular risk.

PMID- 21180891
TI  - Intramyocardial adrenergic activation in chagasic cardiomyopathy and coronary
      artery disease.
AB  - BACKGROUND: Myocardial norepinephrine is altered in left ventricular impairment.
      In patients with Chagas' cardiomyopathy (CC), this issue has not been addressed.
      OBJECTIVE: To determine the level of myocardial norepinephrine in patients with
      CC and compare it in patients with coronary artery disease, and to relate
      myocardial norepinephrine to left ventricular ejection fraction (LVEF). METHODS:
      We studied 39 patients with CC, divided into group 1: 21 individuals with normal
      LVEF and group 2: 18 individuals with decreased LVEF. Seventeen patients with
      coronary artery disease were divided into group 3: 12 individuals with normal
      LVEF and group 4: 5 individuals with decreased LVEF. Two-dimensional
      echocardiography was used to measure LVEF. Myocardial norepinephrine was
      determined by high-performance liquid chromatography. RESULTS: Myocardial
      norepinephrine in CC with and without ventricular dysfunction was 1.3+/-1.3 and
      6.1+/-4.2 pg/MUg noncollagen protein, respectively (p<0.0001); in coronary artery
      disease with and without ventricular dysfunction, it was 3.3+/-3.0 and 9.8+/-4.2
      pg/MUg noncollagen protein, respectively (p<0.0001). A positive correlation was
      found between LVEF and myocardial norepinephrine concentration in the patients
      with Chagas' cardiomyopathy (p<0.01, r = 0.57) and also in those with coronary
      artery disease (p<0.01, r=0.69). A significant difference was demonstrated
      between norepinephrine concentrations in patients with normal LVEF (groups 1 and
      3; p = 0.0182), but no difference was found in patients with decreased LVEF
      (groups 2 and 4; p = 0.1467). CONCLUSION: In patients with Chagas' cardiomyopathy
      and normal global ejection fraction there is an early cardiac denervation, when
      compared to coronary artery disease patients.

PMID- 21180892
TI  - Sidestream cigarette smoke exposure effects on baroreflex in adult rats.
AB  - BACKGROUND: It has been evidenced in the literature that exposure to cigarette
      smoke causes hypertension in rats; however, it has not been demonstrated if the
      baroreflex function is impaired before the animal becomes hypertensive.
      OBJECTIVE: We evaluated short-term effects of sidestream cigarette smoke (SSCS)
      exposure on baroreflex function in Wistar normotensive rats. METHODS: Rats were
      exposed to SSCS during three weeks, 180 minutes, five days per week, at a
      concentration of monoxide carbon between 100-300 ppm. Mean arterial pressure
      (MAP) and heart rate (HR) were evaluated through cannulation of the femoral vein
      and artery. RESULTS: There was no significant difference between control and SSCS
      groups regarding basal mean arterial pressure and heart rate, sympathetic and
      parasympathetic components of the baroreflex function. CONCLUSION: Our data
      suggest that three weeks of exposure to SSCS is not enough to significantly
      impair cardiovascular parameters and baroreflex sensitivity in normotensive
      Wistar rats.

PMID- 21180893
TI  - Association between inflammatory markers and cardiovascular risk factors in women
      from Kolkata, W.B, India.
AB  - BACKGROUND: Recent research has focused on the use of inflammatory biomarkers in
      the prediction of cardiovascular risk. However, information is scant regarding
      the association between these inflammatory markers with other cardiovascular risk
      factors in Asian Indians, particularly in women. OBJECTIVE: To explore the
      association between inflammatory markers such as high-sensitivity C-reactive
      protein (hs-CRP) and white blood cell (WBC) count and cardiovascular risk factors
      such as overall and central adiposity, blood pressure, lipid and lipoprotein
      variables and fasting glucose. METHODS: We conducted a cross-sectional analysis
      on 100 women aged 35-80 years. Participants were selected following cluster
      sampling methodology from 12 different randomly selected urban wards of Kolkata
      Municipal Corporation. RESULTS: Hs-CRP has a significant association with body
      mass index (BMI) ( p < 0.001) and waist circumference (WC) (p = 0.002).
      Significant inverse associations were observed between high-density lipoprotein
      cholesterol (HDL-C) and both inflammatory markers, hs-CRP (p = 0.031) and WBC
      count, (p = 0.014). Apolipoprotein A1 (Apo A1) was also negatively associated
      with hs-CRP. WBC count has significant correlation with fasting glucose and total
      cholesterol (TC) /HDL-C ratio. Using logistic regression, adjusting for age, BMI
      (odds ratio/OR, 1.186; confidence interval/CI, 1.046-1.345; p = 0.008) and WC
      (OR, 1.045; CI, 1.005-1.087; p = 0.027) were the covariates significantly
      associated with hs-CRP. CONCLUSION: In the present study, risk factors like BMI,
      WC, and HDL-C and apo A1 show significant association with hs-CRP. WBC count was
      significantly correlated with HDL-C, fasting glucose, TC/HDL-C ratio in women.

PMID- 21180894
TI  - Combining multiple models to predict the geographical distribution of the Baru
      tree (Dipteryx alata Vogel) in the Brazilian Cerrado.
AB  - The Brazilian Cerrado is a biome of great biodiversity, but detailed information
      about the diversity and distribution of species in this region is still
      insufficient for both testing ecological hypotheses and for conservation
      purposes. Among native plants in the Cerrado, Dipteryx alata Vogel (commonly
      known as the "Baru" tree), has a high potential for exploitation. The aims of
      this paper were to predict the potential spatial distribution of D. alata in the
      Brazilian Cerrado utilising five different niche modelling techniques. These
      techniques usually provide distinct results, so it may be difficult to choose
      amongst them. To adjust for this uncertainty, we employ an ensemble forecasting
      approach to predict the spatial distribution of the Baru tree. We accumulated a
      total of 448 occurrence points and modelled the subsequent predicted occurrences
      using seven climatic variables. Five different presence-only ecological niche
      modelling techniques (GARP, Maxent, BIOCLIM, Mahalanobis Distance and Euclidean
      Distance) were used and the performance of these models was compared using
      Receiver Operating Characteristics (ROC) and the Area Under the Curve (AUC). All
      models presented AUC values higher than 0.68, and GARP presented the highest AUC
      value, whereas Euclidean Distance presented the lowest. The ensemble forecasting
      approach suggested a high suitability for the occurrence of the Baru tree in the
      Central-Western region of the Brazilian Cerrado. Our study demonstrated that
      modelling species distribution using ensemble forecasting can be an important
      computational tool for better establishing sampling strategies and for improving
      our biodiversity knowledge to better identify priority areas for conservation.
      For the Baru tree, we recommend priority actions for conservation in the central
      region of the Cerrado Biome.

PMID- 21180895
TI  - Epipsammic diatoms in streams influenced by urban pollution, Sao Carlos, SP,
      Brazil.
AB  - Epipsammic diatoms have important implications for ecosystem processes in lotic
      environments. Most of the studies on benthic diatoms concentrate on epilithic
      diatoms and very little is known about epipsammic diatoms. The objective of this
      study was to assess epipsammic diatom communities in streams in relation to
      environmental conditions. Epipsammic diatoms and water quality sampling was done
      at 7 sites during summer base flow period (2008). Forward stepwise multiple
      regression and canonical correspondence analysis (CCA) were used to determine
      environmental gradients along which species vary with physical and chemical
      variables. A total of 112 diatom species distributed among 44 genera were
      recorded. Altitude and the process of eutrophication played a significant role in
      structuring diatom communities in the study region.

PMID- 21180896
TI  - Potential of Metarhizium anisopliae (Metsch.) Sorokin (Ascomycetes, hypocreales)
      in the control of Bonagota salubricola (Meyrick) (Lepidoptera, Tortricidae) and
      its compatibility with chemical insecticides.
AB  - Several insects are harmful to apples grown in Brazil, especially the leafroller
      Bonagota salubricola (Lepidoptera, Tortricidae), usually controlled with chemical
      insecticides. The purpose of the present study was to investigate the use of
      Metarhizium anisopliae strains in the control of the apple leafroller, by
      assessing their virulence to B. salubricola larvae in bioassays with suspensions
      of 2 x 105 to 2 x 109 conidia/mL as well as their relationship with protease
      expression. The most effective strain underwent a compatibility test with
      chemical insecticides. The M. anisopliae E6 strain showed a good performance,
      with up to 88% mortality and a LT50 of 1.66 days. The virulence was positively
      correlated with a higher enzymatic activity. The E6 strain was compatible with
      tebufenozide, evidencing its potential to control B. salubricola.

PMID- 21180897
TI  - Time and seasonal patterns of activity of phyllostomid in fragments of a
      stational semidecidual forest from the Upper Parana River, Southern Brazil.
AB  - Bats may exhibit different patterns of activity, considering aspects concerning
      niche dynamics as well as the establishment and permanence of the communities in
      the ecosystems. In this way, the present study analyzed the time and seasonal
      patterns of activity in different species of frequent phyllostomid bats in
      remnants of the stational semidecidual forest from the Upper Parana River,
      Southern Brazil. Captures were performed between January and December, 2006,
      using 32 mist nets set above the soil along the nocturnal period during the four
      seasons of the year. The daily and seasonal patterns of activity of each species
      was modeled using generalized linear models with Poisson error. The best model
      was selected using Akaike's Information Criterion (AICc). Artibeus planirostris
      (Spix, 1823) did not exhibit a conspicuous time pattern, whereas A. lituratus
      (Olfers, 1818) was more frequent after the sixth hour and A. fimbriatus Gray,
      1838 had an activity increase along the night. Platyrrhinus lineatus (E.
      Geoffroy, 1810) was registered during all sampling hours. Carollia perspicillata
      (Linnaeus, 1758) and Sturnira lilium (E. Geoffroy, 1810) were the most active
      during the first four hours. Concerning seasonal pattern, the highest activity of
      these species was verified during the summer. These data contribute to the
      information about the ecology of bats in the region, highlighting the high
      adaptive potential of the species studied in relation to the use of space
      throughout the night and in to variations in environmental conditions.

PMID- 21180898
TI  - Small-scale marine fisheries in the municipal district of Florianopolis, Santa
      Catarina, Brazil.
AB  - The objective of this paper is to describe the main characteristics of small
      scale marine fisheries in the municipal district of Florianopolis (SC), the
      capital city of the state of Santa Catarina. We give information about the most
      captured species, the fishing fleet and fishing gear used. The dynamics of the
      activity is described, considering the kind of operation of the boats, alongside
      post-capture procedures. The analyses were accomplished in two types of fishing
      communities: the one composed of fishers that fish in bays (North and South) and
      those who fish in the open sea. Numeric differences were observed among these two
      fishing areas, indicating the existence of two different fleets operating in the
      area. Differences between the two fishing areas were detected, considering the
      species caught, the harvest time and the fishing gear used. The open sea fishers
      have boats with dimensions, engine power, number of crew and fuel consumption
      numerically higher than those working in bays, indicating the existence of two
      distinct fleets operating in the region.

PMID- 21180899
TI  - Living together, sometimes feeding in a similar way: the case of the syntopic
      hylid frogs Hypsiboas raniceps and Scinax acuminatus (Anura: Hylidae) in the
      Pantanal of Miranda, Mato Grosso do Sul State, Brazil.
AB  - We studied the feeding ecology of two Hylinae anurans (Hypsiboas raniceps and
      Scinax acuminatus), living sympatrically and syntopically in the Pantanal of
      Miranda, Mato Grosso do Sul State, Brazil. The two hylid species had similar
      relative mouth width but differed in body size. The diet of the two frog species
      were composed of arthropodan prey. Both species consumed 11 different prey types,
      of which seven were common among them. Hypsiboas raniceps had a larger niche
      breadth (B(A) = 0.64) than S. acuminatus (B(A) = 0.48). Trophic niche overlap
      among frog species was 60.7 %. Our data are suggestive that although for many
      anurans the diet simply tend to reflect prey availability in the microhabitat,
      these two frog species, despite sharing similar microhabitat and period of
      activity (thus potentially exposed to a similar array of preys), tends to differ
      somewhat in diet (about 40%) which may result from some intrinsic ecological
      aspects to each of them (e.g. ecophysiology) and/or differences in body size.

PMID- 21180900
TI  - Distribution of populations of broad-snouted caiman (Caiman latirostris, Daudin
      1802, Alligatoridae) in the Sao Francisco River basin, Brazil.
AB  - We surveyed populations of the broad-snouted caiman, Caiman latirostris,
      throughout the Sao Francisco River basin, from Tres Marias reservoir, State of
      Minas Gerais, to the river delta, at the boarder of Sergipe and Alagoas states.
      We registered the occurrence of crocodilians in 61% of all surveyed localities (n
      = 64), in which the presence of C. latirostris was confirmed in 44% of the
      surveyed sites. Caimans occurred in both lentic and lotic habitats, although
      there was a preference for small dams, oxbow lakes and wetlands. Despite the
      hunting pressure and human impact on natural habitats, our results indicate that
      the populations of C. latirostris in the Sao Francisco basin are not fragmented.

PMID- 21180901
TI  - Anthropization on the Cerrado biome in the Brazilian Urucui-Una Ecological
      Station estimated from orbital images.
AB  - In this study we analysed the dynamics of deforestation and burnings during the
      dry seasons from 2003 to 2008 in the Urucui-Una Ecological Station (UUES) and its
      buffer zone, located in the Cerrado biome of the southwest of Piaui, a Brazil's
      State, based on images from the orbital sensors CCD/CBERS-2 and TM/Landsat-5. Two
      dates from each of the years were interpreted and analysed: one in the middle of
      the dry season and one at the end. The deforested areas were expanded through the
      period analysed and were larger in the buffer zone, suggesting a relative
      protection of the UUES. New cut-offs were predictable because of the early
      opening of roads that would become their limits. The burning scars were larger at
      the end of the dry season as a consequence of the management and implementation
      of agricultures and pastures. In 2004 and 2007 these scars were larger probably
      because of the increase of dry phytomass that every three years is big enough to
      spread the fire originated in the anthropogenic burnings through the native
      vegetation. This scenario reaffirms the need for: stronger enforcement in order
      to stop anthropisation in the UUES and a management plan, absent for this unit so
      far. These proceedings are urgent also because the UUES is located in one of the
      most preserved regions of the Cerrado and controversially where intense
      anthropisation in ongoing, which stresses the lack, need and urgency of
      biological conservation proceedings for the Piaui's southeastern Cerrado.

PMID- 21180902
TI  - Germination and initial growth of Campomanesia xanthocarpa O. Berg. (Myrtaceae),
      in petroleum-contaminated soil and bioremediated soil.
AB  - In 2000 there was an oil spill at the Getulio Vargas Refinery (REPAR) in Parana.
      Nearly five years after contamination and the use of bioremediation, a study was
      carried out to identify the effects of the contaminated soil and the
      bioremediated soil on the germination and initial growth of C. xanthocarpa. The
      experiment was established with soil from REPAR, with three treatment groups:
      contaminated soil (C), bioremediated soil (B) and uncontaminated soil (U); with
      five repetitions of 50 seeds each. There was no significant difference in the
      percentage of germination and the speed of germination index. The production of
      total biomass (30 - 60 days) and shoot biomass (60 days) was greater in the
      bioremediated soil compared to the other treatments. The averages for the root
      biomass were lower in the contaminated soil than in the bioremediated soil. The
      shoot length and the total length of the seedling in the contaminated soil and
      uncontaminated soil were lower than in the bioremediated soil.

PMID- 21180903
TI  - Domestic dogs in a fragmented landscape in the Brazilian Atlantic Forest:
      abundance, habitat use and caring by owners.
AB  - This study aimed at estimating the population size and attitudes of residents
      towards caring for domestic dogs, through questionnaire surveys, as well as the
      frequency of these animals in different habitats (anthropic and forest patch),
      using scent stations. The study was conducted in a severely fragmented area of
      the Brazilian Atlantic Forest. A large number of unrestricted dogs was recorded,
      averaging 6.2 ind/km2. These dogs have owners and are regularly fed. Dog records
      decreased from the anthropogenic matrix to the forest patch edge, which suggests
      that dogs act as an edge effect on forest patches. Encounters between domestic
      dog and wild animals can still be frequent in severely fragmented landscapes,
      mainly at the forest edges. However the fact that most dogs have an owner and are
      more frequent in the anthropic habitat suggests that their putative effects are
      less severe than expected for a carnivore of such abundance, but the
      reinforcement of responsible ownership is needed to further ameliorate such
      effects.

PMID- 21180904
TI  - Diversity of larvae of littoral Chironomidae (Diptera: Insecta) and their role as
      bioindicators in urban reservoirs of different trophic levels.
AB  - The Chironomidae (Diptera: Insecta) have a high species richness, with species
      adapted to live under widely different environmental conditions. The study of the
      taxonomic composition of chironomid larvae and the percentage of occurrence of
      deformities in mouthparts, mainly in the mentum, are used in biomonitoring
      programmes in order to obtain information on the levels of organic and chemical
      pollution of aquatic ecosystems. The objective of this study was to evaluate the
      abundance of chironomid larvae and to quantify the occurrence of mentum
      deformities in the specimens collected in three urban reservoirs with different
      trophic levels. The reservoirs are located in the hydrographic basin of the
      Paraopeba River, an affluent of the Sao Francisco River basin (Minas Gerais
      State, southeastern Brazil). The Serra Azul Reservoir is oligotrophic, the Vargem
      das Flores Reservoir is mesotrophic, and the Ibirite Reservoir is eutrophic.
      Along the littoral zone of each reservoir, 30 samples were collected during each
      sampling campaign. Sampling was carried out every three months for one year, with
      two sampling campaigns during the wet season and two during the dry season in
      2008. Physical and chemical parameters measured in the water column included the
      water depth, Secchi depth, air and water temperature, electrical conductivity,
      total dissolved solids, redox potential, dissolved oxygen, pH, turbidity, Total
      N, Total-P, P-ortho, and chlorophyll-a. The chironomid larvae were identified to
      the genus level. The structure of the chironomid assemblages was evaluated based
      on taxonomic richness (24 genera), density, equitability, and diversity. The
      potential indicator taxa for each reservoir were established through an Indicator
      Species Analysis. The values for taxonomic richness (20 taxa), equitability
      (0.737), and Shannon-Wiener diversity (2.215) were highest in the Serra Azul
      Reservoir. Fissimentum was the indicator taxon in Serra Azul, the oligotrophic
      reservoir; whereas Pelomus was the indicator taxon in Vargem das Flores, and
      Chironomus in Ibirite. The highest percentage of mentum deformities was found
      during the dry season in Serra Azul (6.9%), while the lowest percentage was found
      during the wet season in Vargem das Flores (0.8%). The results of this study
      evidenced significant differences in the taxonomic composition, richness,
      equitability, and diversity of the chironomid assemblages in these three
      reservoirs of different trophic levels.

PMID- 21180905
TI  - Toxic cyanobacteria in reservoirs in northeastern Brazil: detection using a
      molecular method.
AB  - Cyanobacterial blooms are a frequent occurrence in northeastern Brazil and
      constitute a serious public health problem. Using the polymerase chain reaction
      (PCR) method, eleven environmental samples with cyanobacteria from seven
      reservoirs were used to determine the presence of the gene involved in
      microcystin biosynthesis (mcyB). Two sets of oligonucleotide primers were
      designed from the sequencing of Brazilian populations of microcystin producing
      cyanobacteria (mcyB-F/R and mcyB-F/R-A). The presence of the mcyB gene involved
      in microcystin biosynthesis was found in all samples, indicating the potential of
      this gene for producing the toxin. The PCR method proved sensitive and
      appropriate for the detection of potential producers of microcystins in
      environmental samples. Its ability to reveal potentially toxic cyanobacteria
      demonstrates that it can be a valuable tool in the monitoring of blooms.

PMID- 21180906
TI  - Foraging activity of the free-tailed bat Molossus molossus (Chiroptera;
      Molossidae) in southeastern Brazil.
AB  - Sunset and sunrise regulate the activities of most studied bat species. To verify
      patterns of foraging activity, 29 bat sampling nights were carried out over a dam
      in Rio de Janeiro city, which resulted in 363 hours with 730 captures,
      representing 13 species of insectivorous bats. Molossus molossus constituted the
      bulk of the captures (79.9%) and was present in 82.8% of the sampling nights.
      This bat species exhibited crepuscular and nocturnal activity (from -6 minutes to
      900 minutes after the time of sunset). A bimodal activity pattern was observed,
      and two non-overlapping capture peaks. The first peak lasted from 6 minutes
      before sunset to 420 minutes after sunset. The second peak began at 564 minutes
      after sunset and ended just after sunrise. The first capture peak was observed in
      75.9% of the nights, and the second peak in 62.1% of the nights. The time of the
      first capture exhibited a positive linear relationship with sunset and the time
      of the last capture, a positive linear relationship with sunrise. The existence
      of a relationship between night length and the difference between first and last
      captures of each night shows that M. molossus has longer activity the longer the
      night, showing a seasonal variation in the activity period.

PMID- 21180907
TI  - Seed germination and seedling emergence of the invasive exotic species, Clausena
      excavata.
AB  - The aims of this study were to evaluate the effects of light and temperature on
      seed germination and the effect of light on seedling emergence of Clausena
      excavata, an invasive exotic species. Seeds were incubated at constant
      temperatures (10 to 40 oC), under continuous white light and darkness. Seedling
      emergence was evaluated under full sun and canopy shade. There was no significant
      difference between seeds germinated in the presence or absence of light at
      temperatures between 20 and 35 oC. Seeds maintained at 20 oC germinated more
      slowly than other temperatures. Independent of temperature, seed germination was
      much more synchronised under white light than under darkness. In the field,
      emergence occurred in both environments, but a greater percentage was observed
      under full sun. Seedling emergence occurred at the same rate and synchronisation
      index under both conditions. C. excavata has a high invader potential in open
      areas and shaded environments.

PMID- 21180908
TI  - Cage culture with tilapia induces alteration in the diet of natural fish
      populations: the case of Auchenipterus osteomystax.
AB  - Fish rearing in cages installed in reservoirs has developed rapidly in Brazil
      over the last decade. However, this type of aquaculture induces some changes in
      the environment because of the high quantity of nutrients released into the
      surroundings. This study evaluated trophic changes resulting from these nutrient
      inputs into the diet, feeding activity and nutritional condition of Auchenipterus
      osteomystax, an insectivore that alternatively feeds on zooplankton. Fish were
      sampled with gillnets in two tilapia (Oreochromis niloticus) experimental caging
      aquaculture areas of the Rosana reservoir (Paranapanema River), at different
      distances from the cages. Samplings were carried out for 90 days (before the
      cages were installed and 30 and 60 days after installation). Diet analysis was
      based on 250 stomach contents evaluated with occurrence and volumetric methods,
      combined into a Feeding Index. The spatial and temporal variations in feeding
      activity were inferred by the stomach repletion index (stomach weight). The
      relative condition factor was used to evaluate the individual nutritional
      condition of the sampled fish. Insects and zooplankton accounted for more than
      85% of the diet in any sample. Insects predominated before caging culture started
      and at the end of the sampling period, whereas zooplankton predominated 30 days
      after caging began. The repletion index increased at 30 days after caging in both
      areas when the condition factor was the lowest, with some recovery at the end of
      this period. The input of nutrients near caging areas caused a short elevation in
      zooplankton availability, which promoted changes in the diet of this opportunist
      species, increasing its feeding activity. However, these changes appeared to be
      unsustainable due to the poor nutritional condition of the individuals.

PMID- 21180909
TI  - Potential heterogeneity in crustacean zooplankton assemblages in southern chilean
      saline lakes.
AB  - The Chilean saline lakes are distributed mainly in the Atacama desert in northern
      Chile and the southern Patagonian plains. The scarce studies are restricted
      mainly to northern Chilean saline lakes, and these revealed that the main
      component in these ecosystems are the halophylic copepod Boeckella poopoensis
      Marsh 1906, or the brine shrimp Artemia franciscana (Kellog, 1906), and both
      species do not coexist. The present study consisted of field observations in
      zooplankton assemblages in southern Chilean saline lakes (51-53 oS). These first
      observations revealed three different patterns, one saline lake only with A.
      persimilis (Piccinelli and Prosdocimi, 1968), a second lake only with B.
      poopensis, and a third lake with A. persimilis, B. poopoensis and unidentified
      harpacticoid copepod. These results are different in comparison with the
      observations in the literature that described the non-coexistence between B.
      poopoensis with brine shrimps. Ecological and biogeographical topics were
      discussed.

PMID- 21180910
TI  - Seasonal and ontogenetic variations in the diet of Cichla kelberi Kullander and
      Ferreira, 2006 introduced in an artificial lake in southeastern Brazil.
AB  - The diet of Cichla kelberi introduced in an artificial lake in Leme-SP was
      predominantly composed of common fish species (Oreochromis niloticus and C.
      kelberi). In the spring and summer, the most consumed item was O. niloticus.
      However, cannibalism was very common for this species. The high frequencies of O.
      niloticus and C. kelberi reveal that this species is adapted to a seasonal cycle,
      feeding on the most common prey in each period of the year, with a reduction of
      foraging activity during the winter. The diets were different among the immature
      and mature individuals suggesting that there are ontogenetic differences, mainly
      related to prey type, such as: Ephemeroptera consumed by the immature peacock
      bass and fish by the mature ones, besides the size of the prey.

PMID- 21180911
TI  - Bacillus thuringiensis isolates entomopathogenic for Culex quinquefasciatus
      (Diptera: Culicidae) and Anticarsia gemmatalis (Lepidoptera: Noctuidae).
AB  - Samples of the Bacillus thuringiensis (Bt) were collected from soil and insects.
      Eight isolates were selected from rural soil, 15 from urban soil and 11 from
      insects. These were evaluated for entomopathogenicity against larvae of
      Anticarsia gemmatalis and Culex quinquefasciatus. The pathogenicity tests showed
      that a higher percentage of isolates were active against A. gemmatalis (60%)
      compared to C. quinquefasciatus (31%). Probit analysis (LC50) indicated that
      against A. gemmatalis four of the isolates presented values similar to the
      reference strain against A. gemmatalis, while against C. quinquefasciatus one
      isolate showed an LC50 similar to the reference strain (IPS-82). SDS-PAGE
      characterisation of two isolates showed a 27 kDa protein fraction related to the
      Bt subspecies israelensis cytolytic toxin (cyt) gene. One 130 kDa protein,
      possibly related to the Bt crystal inclusions (cry1) gene, was identified in the
      other two isolates, which were more toxic for lepidoptera; another isolate
      presented a protein of 100 kDa. Some new local Bt isolates had similar LC50
      probit values to the reference strains.

PMID- 21180912
TI  - Colony size, sex ratio and cohabitation in roosts of Phyllostomus hastatus
      (Pallas) (Chiroptera: Phyllostomidae).
AB  - Phyllostomus hastatus bat is species broadly distributed over the Neotropical
      region, which uses as diurnal roosts caves, hollow trees, palm leaves and human
      buildings. Thirteen diurnal roosts of P. hastatus were analysed from 1990 to 2009
      in several localities of Rio de Janeiro State, regarding environment (rural,
      urban or protected area), type of roost (hollow tree, basement or roof), sex
      ratio and cohabitation. A nocturnal roost was also analysed. Sex ratio of P.
      hastatus varied considerably among roosts what may be explained by the fact this
      species can roost alone, in couples, in harems or in groups of bachelor males.
      Phyllostomus hastatus was observed in cohabitation with three other species:
      Molossus rufus, Molossus molossus and Myotis nigricans. Due to the frequency of
      cohabitation observed between P. hastatus and species of the genus Molossus, one
      or more advantages for the members of this association may be expected. The
      simultaneous usage of a feeding roost by a group of bachelor males is unknown
      information in the literature, and may suggest that this kind of group may
      interact with each other even when away from their diurnal roosts.

PMID- 21180913
TI  - Occurrence of Chaetogaster limnaei K. von Baer, 1927 (Oligochaeta, Naididae)
      associated with Gastropoda mollusks in horticultural channels in Southeastern
      Brazil.
AB  - The aim of this study was to evaluate the presence of Chaetogaster limnaei K. von
      Baer, 1927 in four species of mollusks collected in irrigation channels of a
      horticultural garden in the city of Juiz de Fora, Minas Gerais State,
      Southeastern Brazil. The collections were made from June 2005 to January 2006. Of
      the four species of mollusks analysed, we could not detect the presence of C.
      limnaei in Pomacea lineata (Spix, 1827). There were recorded 320 specimens of C.
      limnaei in association with Aplexa rivalis Mastou & Rackett, 1898, Lymnaea
      columella Say, 1818 and Biomphalaria sp., the latter having the highest number of
      associated Naididae.

PMID- 21180914
TI  - Description of the female, pupa and gall of Pisphondylia brasiliensis Couri and
      Maia, 1992 (Diptera: Cecidomyiidae, Schizomyiina) with new records.
AB  - The gall of Pisphondylia brasiliensis on Guapira opposita, its female and pupa
      are described and illustrated. The geographic distribution of this species is now
      widened to Minas Gerais and Rio Grande do Sul (Brazil). For the first time, a
      female of the genus is described.

PMID- 21180915
TI  - Antimicrobial potential of some plant extracts against Candida species.
AB  - The increase in the resistance to antimicrobial drugs in use has attracted the
      attention of the scientific community, and medicinal plants have been extensively
      studied as alternative agents for the prevention of infections. The Candida genus
      yeast can become an opportunistic pathogen causing disease in immunosuppressive
      hosts. The purpose of this study was to evaluate dichloromethane and methanol
      extracts from Mentha piperita, Rosmarinus officinalis, Arrabidaea chica, Tabebuia
      avellanedae, Punica granatum and Syzygium cumini against Candida species through
      the analysis of Minimum Inhibitory Concentration (MIC). Results presented
      activity of these extracts against Candida species, especially the methanol
      extract.

PMID- 21180916
TI  - Nuclear activity in Apis mellifera L. (Hymenoptera, Apidae) queen ovary cells
      demonstrated by silver nitrate impregnation and ultrastructure.
AB  - The present paper shows through conventional light microscopy, silver nitrate
      impregnation and Transmission Electron Microscopy, the changes in nuclear
      activity that occurs in the ovary cells during vitellogenesis of Apis mellifera
      (Linnaeus, 1758). The material impregnated by silver nitrate was detected in
      nurse cells, oocyte germinal vesicle and follicular cells, whose amounts are
      greater in phases corresponding to ovarian cells more intense activity. The
      silver impregnation permitted to demonstrate that the oocyte germinal vesicle
      synthezises ribonucleoproteins (RNP) during the beginning of the vitellogenesis.
      The ultrastructure show nucleolar-like material corresponding to nuclear sites
      impregnated by silver.

PMID- 21180917
TI  - Apis mellifera (Hymenoptera: Apidae) as a potential Brassica napus pollinator
      (cv. Hyola 432) (Brassicaceae), in Southern Brazil.
AB  - Brassica napus Linnaeus is considered a self-compatible crop; however, studies
      show that bee foraging elevates their seed production. Considering bee food
      shortages during the winter season and that the canola is a winter crop, this
      study aimed to evaluate the foraging behaviour of Apis mellifera Linnaeus, 1758
      regarding those flowers, and to verify if it presents adequate behaviour for
      successfully pollinating this crop in Rio Grande do Sul State. The study was
      carried out in a canola field, in Southern Brazil. The anthesis stages were
      morphologically characterised and then related to stigma receptivity and pollen
      grain viability. Similarly, the behaviour of A. mellifera individuals on flowers
      was followed, considering the number of flowers visited per plant, the amount of
      time spent on the flowers, touched structures, and collected resources. Floral
      fidelity was inferred by analysing the pollen load of bees collected on flowers.
      The bees visited from 1-7 flowers/plant (x = 2.02; sd = 1.16), the time spent on
      the flowers varied between 1-43 seconds (x = 3.29; sd = 2.36) and, when seeking
      nectar and pollen, they invariably touched anthers and stigmas. The pollen load
      presented 100% of B. napus pollen. The bees' attendance to a small number of
      flowers/plants, their short permanence on flowers, their contact with anthers and
      stigma and the integral floral constancy allows their consideration as potential
      B. napus pollinators.

PMID- 21180918
TI  - What is the influence of ordinary epidermal cells and stomata on the leaf
      plasticity of coffee plants grown under full-sun and shady conditions?
AB  - Stomata are crucial in land plant productivity and survival. In general, with
      lower irradiance, stomatal and epidermal cell frequency per unit leaf area
      decreases, whereas guard-cell length or width increases. Nevertheless, the
      stomatal index is accepted as remaining constant. The aim of this paper to study
      the influence of ordinary epidermal cells and stomata on leaf plasticity and the
      influence of these characteristics on stomata density, index, and sizes, in the
      total number of stomata, as well as the detailed distribution of stomata on a
      leaf blade. As a result, a highly significant positive correlation (R2(a) = 0.767
      p <= 0.001) between stomatal index and stomatal density, and with ordinary
      epidermal cell density (R2(a) = 0.500 p <= 0.05), and a highly negative
      correlation between stomatal index and ordinary epidermal cell area (R2(a) = 
      0.571 p <= 0.001), were obtained. However in no instance was the correlation
      between stomatal index or stomatal density and stomatal dimensions taken into
      consideration. The study also indicated that in coffee, the stomatal index was
      19.09% in shaded leaves and 20.08% in full-sun leaves. In this sense, variations
      in the stomatal index by irradiance, its causes and the consequences on plant
      physiology were discussed.

PMID- 21180919
TI  - Larval nematodes found in amphibians from northeastern Argentina.
AB  - Five species of amphibians, Leptodactylus podicipinus, Scinax acuminatus, S.
      nasicus, Rhinella fernandezae and Pseudis paradoxa, were collected in Corrientes
      province, Argentina and searched for larval nematodes. All larval nematodes were
      found as cysts in the serous of the stomach of hosts. Were identified one
      superfamily, Seuratoidea; one genus, Spiroxys (Superfamily Gnathostomatoidea) and
      one family, Rhabdochonidae (Superfamily Thelazioidea). We present a description
      and illustrations of these taxa. These nematodes have an indirect life cycle and
      amphibians are infected by consuming invertebrate, the intermediate hosts. The
      genus Spiroxys and superfamily Seuratoidea were reported for the first time for
      Argentinean amphibians.

PMID- 21180920
TI  - Growth and mortality of Cichla spp. (Perciformes, Cichlidae) introduced in Volta
      Grande Reservoir (Grande River) and in a small artificial lake in Southeastern
      Brazil.
AB  - The growth and mortality parameters were estimated through the analysis of length
      frequency distribution for species of Cichla spp. introduced into a lake in Leme
      (SP), and in Volta Grande reservoir (SP-MG). In Leme, Cichla kelberi presented
      larger frequency in the inferior classes of lengths, larger instantaneous rate of
      natural mortality, and smaller number of cohorts than C. kelberi and C. piquiti
      in Volta Grande. The values of growth performance obtained for the species were
      similar, corroborating the validity of the estimated growth and mortality
      parameters. The increase of the growth rate in small and less diverse
      environments occurs due to predation. The genus Cichla adapts well in locations
      in which it is introduced, however this adaptation shows itself to be strongly
      adjusted to each particular location, determining great plasticity and
      establishment capacity.

PMID- 21180921
TI  - Two new species of Pedinotus Szepligeti 1902 (Hymenoptera: Braconidae:
      Doryctinae) from the Savannah in Sao Paulo state, Brazil.
AB  - Two new species of Pedinotus genus are described from the Brazilian savannah
      area, providing a new key to identify the species.

PMID- 21180922
TI  - Evaluation of a new formulation of Bacillus thuringiensis israelensis.
AB  - The aim of this study was to determine the potency (ITU) and efficacy of a liquid
      formulation of Bacillus thuringiensis israelensis developed by the State
      University of Londrina named BioUel, against early fourth instar larvae of Aedes
      aegypti and Culex quinquefasciatus. The ITU/mg of BioUel was 960, the LC50 was of
      0.271 (+/- 0.39) ppm, and the LC95 was 0.634 (+/- 0.099) ppm, in larvae of C.
      quinquefasciatus. In A. aegypti larvae, LC50 was 0.332 (+/- 0.042) ppm and LC95
      was 0.694 (+/- 0.073) ppm. The ITU level of BioUel and its control results were
      similar to most commercial products tested. Stability was of approximately 90
      days, which allows for local production.

PMID- 21180923
TI  - Haplotype characterization of the COI mitochondrial gene in Chrysoperla externa
      (Neuroptera: Chrysopidae) from different environments in Jaboticabal, state of
      Sao Paulo, southeastern Brazil.
AB  - The green lacewings (Chrysopidae) belong to the Order Neuroptera and are
      described as voracious predators in the larval stage and sometimes also in their
      adulthood. They are an important group used in integrated biological control in
      field and horticultural crops. Individuals of Chrysoperla externa were collected
      during 2007 until March 2008 in five different locations in Jaboticabal, SP, with
      all the seasons sampled. Thirty six sequences with 805 pairs of bases for the
      gene mitochondrial Citochrome Oxidase I (COI) were analysed. The genetic
      parameters revealed 24 haplotypes for this population, a total of 36 mutations
      and haplotype diversity of 0.956. The data of genetic distance and population
      structure calculated for this population considering the different areas and
      seasons, revealed a great genetic similarity and high degree of genetic sharing
      between individuals sampled. It showed that the species Chrysoperla externa from
      Jaboticabal, SP, is a single population, without genetic structure neither due to
      the area of origin nor to the seasons of the year.

PMID- 21180924
TI  - Diet and feeding daily rhythm of Pimelodella lateristriga (Osteichthyes,
      Siluriformes) in a coastal stream from Serra do Mar - RJ.
AB  - The present study was carried out in Mato Grosso fluvial system, a costal
      drainage from Serra do Mar. We analysed the diet and the feeding daily rhythm of
      Pimelodella lateristriga from samples carried out during 24 hours over a 4 hour
      fishing interval, in June, July and September, 2006 as well as in January and
      February, 2007. Diet was described from the Feeding Index (IAi) and feeding daily
      rhythm was verified through the Gut Fullness Index (GFI). Pimelodella
      lateristriga diet was composed of 37 items, being aquatic insects the most
      important ones. IAi analysis revealed that Diptera, Trichoptera and Ephemeroptera
      amounted to 90% of the diet. Autochthonous invertebrates were the most important
      consumed items. Pimelodella lateristriga concentrated its feeding activities in
      the nocturnal period (10:00 PM to 2:00 AM) with marked significant differences (F
      = 16.11; gl = 5; p < 0.05) between each diurnal and nocturnal periods. Between
      6:00 AM and 6:00 PM, foraging activity was gradually reduced. We concluded that
      P. lateristriga has an insectivorous diet and a nocturnal feeding habit with
      greater activity between 10:00 PM to 2:00 AM.

PMID- 21180925
TI  - Prevention strategies for methicillin-resistant S taphylococcus aureus (MRSA) in
      Latin America.
AB  - After the first reports of the emergence of methicillin-resistant Staphylococcus
      aureus (MRSA) in the 1970s, numerous measures intended to prevent its
      transmission were initiated in hospitals. However, in most cases, large-scale
      measures failed to be implemented and the transmission of MRSA has since led to a
      global pandemic. Presently, doubts still remain about the best approach to
      prevent and control MRSA and more often than not, control measures are not
      implemented. Therefore, we review here the current situation in Latin America
      with respect to existing policies for control of MRSA, and evaluate the evidence
      for control measures in hospitals and the community. We look at the risk factors
      for infection and transmission of MRSA between hospital patients and within
      specific populations in the community, and at the effect of antibiotic usage on
      the spread of MRSA in these settings. Finally, we summarize recommendations for
      the prevention and control of MRSA, which can be applied to the Latin American
      hospital environment and community setting.

PMID- 21180926
TI  - Treatment of methicillin-resistant Staphylococcus aureus in Latin America.
AB  - The global spread of methicillin-resistant Staphylococcus aureus (MRSA) means it
      is now a pathogen of worldwide public health concern. Within Latin America, MRSA
      is highly prevalent, with the proportion of S. aureus isolates that are
      methicillin-resistant on the rise, yet resources for managing the infection are
      limited. While several guidelines exist for the treatment of MRSA infections,
      many are written for the North American or European setting and need adaptation
      for use in Latin America. In this article, we aim to emphasize the importance of
      appropriate treatment of MRSA in the healthcare and community settings of Latin
      America. We present a summary of the available guidelines and antibiotics, and
      discuss particular considerations for clinicians treating MRSA in Latin America.

PMID- 21180927
TI  - Current status and recommendations on methicillin-resistant Staphylococcus aureus
      infection in Latin America.

PMID- 21180928
TI  - Epidemiology and surveillance of methicillin-resistant staphylococcus aureus in
      Latin America.
AB  - Surveillance systems monitoring the spread and divergence of methicillin
      resistant Staphylococcus aureus (MRSA) strains are critical if preventive and
      therapeutic measures targeting MRSA infection are to be employed optimally.
      Surveillance provides information on the spread of MRSA, on the emergence of new
      strains within hospitals and communities, on the antibiotic resistance profile
      and virulence of strains, and on the risk factors associated with infection.
      These data help clinicians to provide appropriate empiric treatment of infections
      circulating in their region, leading to improved patient outcomes. While
      information on MRSA epidemiology in Latin America is growing, significant gaps
      exist in the available data, especially in local areas where fewer resources are
      available for characterizing and reporting MRSA strains. Here, we describe
      current knowledge of healthcare- and community-associated MRSA epidemiology in
      the region, and provide recommendations for future development of surveillance
      systems with a view to providing robust data at regional, national and local
      levels.

PMID- 21180929
TI  - The changing pattern of methicillin-resistant staphylococcus aureus clones in
      Latin America: implications for clinical practice in the region.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) clones belonging to the
      Brazilian, Pediatric, Cordobes/Chilean and New York/Japan clonal complexes are
      widely distributed across Latin America, although their individual distribution
      patterns and resistance to antimicrobial drugs are constantly changing.
      Furthermore, clones with increased virulence are beginning to appear more
      frequently both in hospital and community settings, and there is evidence that
      virulence factors can be transferred between hospital- and community-associated
      clones through recombination. These changing patterns have significant
      implications for clinical practice in the region. Most importantly, clinicians
      need to be aware of the changing antimicrobial resistance profile of circulating
      MRSA clones in their region in order to choose the most appropriate empiric
      antimicrobial therapy. Thus, regional molecular epidemiology programs are
      required across the region to provide accurate identification and
      characterization of circulating MRSA clones.

PMID- 21180930
TI  - Diagnosis and susceptibility testing of methicillin-resistant Staphylococcus
      aureus in Latin America.
AB  - Strategies to monitor and control the spread of methicillin-resistant
      Staphylococcus aureus (MRSA) infections are dependent on accurate and timely
      diagnosis of MRSA in both hospital and community settings. In Latin America,
      significant diversity in diagnostic and susceptibility testing procedures exists
      at the regional, national and local levels. Various tests for S. aureus and MRSA
      are available in clinical settings, but the application of these techniques
      differs between and within countries, and quality control measures are not
      uniformly applied to verify diagnoses. To optimize the diagnosis of MRSA
      infections across Latin America, a more consistent approach is required. This may
      include: adoption and appropriate adaption of specific guidelines for MRSA
      testing, depending on local resources; establishment of a coordinated system for
      quality control; regional access to central reference facilities; education of
      medical and healthcare professionals in best practices; and development of
      systems to evaluate the implementation of guidelines and best practices.

PMID- 21180932
TI  - Postural alterations and pulmonary function of mouth-breathing children.
AB  - Mouth-breathing children have changes in their stomatognathic system, which
      result in head projection, stress increase in the scapular belt muscles and
      postural adaptations. Although thoracic shape and posture can influence
      ventilatory dynamics, we didn't find studies addressing pulmonary function of
      mouth-breathing children. AIMS: this study aimed at analyzing the posture of
      mouth-breathing children, and studying the existence of correlations between
      posture and pulmonary volumes. MATERIAL AND METHODS: prospective, observational
      and cross-sectional study, where the posture and pulmonary function of 17 mouth
      breathing children and of 17 nasal-breathing children were evaluated by means of
      photogrammetry and forced spirometry. RESULTS: when compared to nasal-breathing,
      mouth-breathing subjects presented an increment in head projection and cervical
      lordosis, forwarded gravity center and reduced pulmonary volumes. There was an
      association between head projection and forced vital capacity, and between
      postural alterations and age. CONCLUSION: mouth-breathing children have postural
      alterations which increases with age and also reduced spirometry values. The
      vital capacity reduction correlates negatively with head projection.

PMID- 21180933
TI  - High-frequency audiometry in normal hearing military firemen exposed to noise.
AB  - The study of high frequencies has proven its importance for detecting inner ear
      damage. In some cases, conventional frequencies are not sensitive enough to pick
      up early changes to the inner ear. AIM: To analyze the results of threshold high
      frequency analysis of individuals exposed to noise with normal conventional
      audiometry. MATERIALS AND METHODS: This was a retrospective cross-sectional
      cohort study, in which we studied 47 firefighters of the Fire Department of Rio
      de Janeiro, based on Santos Dumont airport and 33 military men without noise
      exposure. They were broken down into two age groups: 30-39years and 40-49years.
      The high frequencies were studied immediately after conventional audiometry.
      RESULTS: The results were most significant in the 40 to 49 years of age range,
      where the experimental group showed significantly higher threshold values than
      the control group 14000Hz (p = 0.008) and 16,000Hz (p = 0.0001). CONCLUSIONS: We
      concluded that noise interfered with high frequency thresholds, where all the
      mean values found in the experimental group were higher than those in the control
      group. We suggest that these data reinforce the importance of studying high
      frequencies, even with normal conventional audiometry in the early detection of
      noise-induced hearing loss.

PMID- 21180934
TI  - Applicability of the University of Pennsylvania Smell Identification Test (SIT)
      in Brazilians: pilot study.
AB  - The University of Pennsylvania Smell Identification Test (SIT) is the most cited
      olfactory test in the literature because it is easy to perform and there is high
      test-retest reliability. There were no standardized olfaction values in a normal
      Brazilian population. AIM: To measure the SIT score in a group of Brazilians, and
      to assess the level of difficulty when implementing the test. STUDY DESIGN: A
      cross-sectional study. MATERIALS AND METHODS: The SIT was applied in 25 Brazilian
      volunteers of various income levels who presented no olfactory complaints.
      Following the test, subjects answered a questionnaire with a visual analog scale
      (VAS) for the level of difficulty. RESULTS: The mean in the sample of Brazilians
      was 32.5 (SD: 3.48) our of 40; this is below what is considered normal for US
      citizens. The level of difficulty was on average 26 mm (SD: 24.68) in the VAS,
      but it trended towards easy; 4(16%) participants did not recognize some of the
      odors under 'alternatives'. CONCLUSION: In this pilot study, there was evidence
      of good test applicability; the score of the sample of Brazilians was just below
      normosmia. Further studies are needed to confirm the existence of differences
      between people of different income levels.

PMID- 21180935
TI  - Diagnostic and therapeutic delay in patients with larynx cancer at a reference
      public hospital.
AB  - Laryngeal squamous cell carcinoma is very often diagnosed at advanced stages. The
      time interval between the specialist consultation and the start of treatment may
      contribute to better outcomes. AIM: the interval assessment between the first
      specialist evaluation and the treatment of patients with laryngeal squamous cell
      carcinoma. STUDY DESIGN: longitudinal historical cohort. MATERIALS AND METHODS:
      272 consecutive patients with laryngeal squamous cell carcinoma seen between
      January, 1996 and December of 2004. Clinical and epidemiological data were
      evaluated, as well as their association with the time interval between the first
      specialist visit and the start of treatment. RESULT: the median time between
      first evaluation and treatment was 49 days. There was no relationship with
      gender, age, birth place, disease stage or education. CONCLUSION: the treatment
      median delay was 49 days, similar to what has been reported in other studies.

PMID- 21180936
TI  - Effect of Epley's maneuver on the quality of life of paroxismal positional benign
      vertigo patients.
AB  - Quality of life (QoL) is significantly impaired by vertigo. The effect of
      specific treatments on QoL deserves investigation. AIM: To assess the effect of
      repositioning maneuvers on the QoL of benign paroxysmal positioning vertigo
      (BPPV) patients. MATERIALS AND METHODS: A retrospective study design consiting of
      reviews of charts of BPPV patients in a vestibular rehabilitation unit at a
      teaching institution in Belo Horizonte, MG, Brazil, from 2007 to 2008. Pre- and
      post-therapy (Epley's repositioning maneuver) scores on the physical, functional
      and emotional dimensions of the Dizziness Handicap Inventory (DHI) were analyzed.
      RESULTS: Twenty-one patients were included, eighteen (86%) were females; the
      average age was 53.2 years. Ten patients presented bilateral BPPV; in eleven it
      was unilateral. The mean interval between assessments (pre- and post-treatment)
      was 21 days. The average number of required maneuvers was 2.3 (+/-1.1). Pre
      treatment DHI results showed a significant impact of BPPV on quality of life.
      Initial scores for physical (17.5), functional (17.3), emotional (13.2)
      dimensions decreased with therapy: respectively 3.7, 3.9, and 3.2 (p<0.001).
      CONCLUSION: In the present sample, Epley's maneuver had a positive and
      significant effect on emotional, physical and functional dimensions of quality of
      life, as measured by the DHI scores before and after therapy.

PMID- 21180937
TI  - Demineralization of teeth in mouth-breathing patients undergoing maxillary
      expansion.
AB  - Mouth breathing may cause deformities on the dental arch and be a risk factor for
      caries and periodontal disease; fixed orthodontic appliances compound the
      problem. AIM: to evaluate mineralization of tooth enamel and the oral cariogenic
      microbiota of mouth breathers that are using maxillary expanders. MATERIAL AND
      METHOD: a prospective study of 20 mouth-breathing patients with maxillary
      atresia, aged from 09 to 13 years. Enamel mineralization was measured using a
      fluorescence technique, before installing the expander and after its removal. The
      cariogenic microbiota was evaluated by the No Caries(r). The t test (p<0.05) was
      applied for the statistical analysis, and the oral microbiota was analyzed by
      incidence. RESULTS: there was a statistically significant difference in the
      enamel mineralization level after maxillary expansion; the mean value was 3.08.
      The colorimetric test showed that the caries development potential was reduced in
      45%, increased in 15%, and unaltered in 40% after maxillary expander use.
      CONCLUSION: there was a statistically significant difference in enamel
      mineralization after maxillary expansion; this difference was within the
      clinically normal range; the cariogenic potential increased in a small number of
      patients during orthodontic treatment.

PMID- 21180938
TI  - Efficacy of cidofovir in recurrent juvenile respiratory papillomatosis.
AB  - The efficacy of cidofovir in juvenile recurrent respiratory papillomatosis (JRRP)
      remains uncertain due to the lack of published case-control studies. AIM: To
      establish factors affecting the progression of JRRP prognosis, and to evaluate
      cidofovir for eradicating JRRP. STUDY DESIGN: Retrospective. METHODS: 22 children
      with JRRP were evaluated at a referral center. All children underwent surgical
      debulking, followed by cidofovir injection (Group 2) or not (Group 1). Age at
      diagnosis was correlated with the Derkay score and disease outcome. Disease
      progression was compared between groups 1 and 2. RESULTS: fifteen children were
      considered disease-free; 8 were in Group 2 and 7 in Group 1. Age and total and
      clinical scores (P<0.05) were negatively correlated. The mean number of surgeries
      required to control the disease was identical in both groups; the duration of
      treatment until remission was significantly higher in Group 1 (P<0,05).
      CONCLUSION: JRRP is more aggressive in earlier onset disease. The duration of
      treatment was significantly lower in patients treated with cidofovir until
      eradication of JRRP compared to patients treated with surgery only.

PMID- 21180939
TI  - Auditory processing in children with normal and disordered speech.
AB  - Phonological speech disorders are characterized by abnormal development towards
      the adult target pattern; its etiology is unknown. It is thought the this
      condition results from auditory processing disorders involving the abilities
      required for human beings to understand what is heard. AIM: To investigate the
      relationship between auditory processing and the acquisition of disordered or
      normal speech, drawing comparisons between these profiles. MATERIAL AND METHOD: A
      prospective, contemporary, cross-sectional study comprising a sample of 44
      subjects aged 5 to 7 years; two groups were formed: a study group (SG) comprising
      children with disordered speech acquisition, and a control group (CG) consisting
      of children with normal speech acquisition. A simplified evaluation of auditory
      processing was undertaken: the PSI test in Portuguese; the speech-in-noise test;
      the binaural fusion test; the dichotic digit test; and the staggered spondaic
      word test (SSW). RESULTS: There was a statistically significant difference
      between the two groups; the SG scored worse than the CG in all the tests. The PSI
      test only - with a 100% success rate - scored equally in both groups. CONCLUSION:
      Auditory processing may affect speech development.

PMID- 21180940
TI  - Auditory steady state response in pediatric audiology.
AB  - The main issue regarding pediatric audiology diagnosis is determining procedures
      to configure reliable results which can be used to predict frequency-specific
      hearing thresholds. AIM: To investigate the correlation between auditory steady
      state response (ASSR) with other tests in children with sensorineural hearing
      loss. METHODS: Prospective cross-sectional contemporary cohort study. Twenty
      three children (ages 1 to 7; mean, 3 years old) were submitted to ASSR,
      behavioral audiometry, click audiometry brain stem response (ABR), tone burst
      ABR, and predicting hearing level from the acoustic reflex. RESULTS: the
      correlation between behavioral thresholds and ASSR was (0.70- 0.93), for the ABR
      tone burst it was (0.73 -0.93), for the ABR click it was (0.83-0.89) only at 2k
      and 4 kHz. The match between the ASSR and the hearing threshold prediction rule
      was considered moderate. CONCLUSION: there was a significant correlation between
      the ASSR and audiometry, as well as between ABR click (2k and 4 kHz) and for the
      ABR tone burst. The acoustic reflex can be used to add information to diagnosis
      in children.

PMID- 21180941
TI  - Auditory Brainstem Evoked Response: response patterns of full-term and premature
      infants.
AB  - Auditory Brainstem Response (ABR) is important for the early diagnosis of hearing
      impairment in infants. AIM: To compare ABR responses in full-term and premature
      infants; gender and ear were taken into account. METHODS: A cross-sectional
      prospective cohort study was carried out. We evaluated 36 full-term and 30
      premature infants that had passed the Transient Otoacoustic Emissions test, had
      type A tympanometric curves, and had no risk factor for hearing loss besides
      prematurity. The evaluations were done from the time of hospital discharge to the
      third month of life, and consisted of a clinical history, acoustic immittance
      testing and ABR evaluation. RESULTS: The comparison of absolute and interpeak
      wave I, III and V latencies in right and left ears revealed a statistically
      significant difference at the interpeak I-III. There was no significant gender
      differences in the comparison of results. Significant difference in wave I, III
      and V absolute latencies at 80 dB and in wave V at 60 db and 20 db were observed
      in a comparison of absolute and interpeak latencies between full-term and
      premature infants. An inverse correlation was found between age and absolute
      latencies. CONCLUSIONS: The maturity of the auditory system influences ABR
      responses in infants. To avoid misinterpretation of results, gestational age must
      be taken into account in the analysis of ABR in pediatric population.

PMID- 21180942
TI  - Prevalence of hearing impairment in children at risk.
AB  - Hearing impairment is prevalent in the general population; early intervention
      facilitates proper development. AIM: To establish the prevalence of hearing
      impairment in infants at risk, born between June 2006 and July 2008, and to
      correlate the variables with hearing loss. TYPE OF STUDY: descriptive and cross
      sectional. MATERIALS AND METHODS: 188 newborns were evaluated using evoked
      otoacoustic emissions and distortion product and auditory behavior. Tests were
      repeated if the results were altered. If altered results persisted, the child was
      referred for impedance testing and, when necessary, for medical evaluation.
      Infants with normal conduction were referred for brainstem auditory evoked
      potential testing. RESULTS: Of 188 children two (1.1%) were excluded, and 174
      (92.6%) had results within normal limits. Hearing impairment was found in 12
      children (6.3%); hearing loss was retrocochlear in three infants (25%).
      Unilateral hearing loss was present in two infants (16.7%); bilateral hearing
      loss was present in 10 infants (83.3%). CONCLUSION: The high prevalence of
      hearing impairment in this population underlines the importance of early
      audiological testing.

PMID- 21180943
TI  - Temporal resolution: performance of school-aged children in the GIN - Gaps-in
      noise test.
AB  - Time resolution hearing skill is the minimum time necessary to solve acoustic
      events, which is fundamental for speech understanding, and which may be assessed
      by gap-detection tests, such as the Gaps-in-noise test (GIN). AIM: the purpose of
      this study was to verify the performance of time processing ability in children
      with no hearing and/or education difficulties by applying the GIN test in both
      genders and ages from 8 to 10 years. STUDY DESIGN: a prospective cross-sectional
      contemporary cohort. MATERIAL AND METHOD: The GIN test was applied to 75 school
      aged children separated into three groups by age. RESULTS: The findings showed no
      statistical differences among age groups or ears. Males had slightly better
      responses than females on the percentage of correct responses only. CONCLUSION:
      The gap threshold and percentage of correct responses were calculated regardless
      of the ear, gender or age, and were respectively 4.7ms and 73.6%. Based on a 95%
      confidence interval, the cut-off criterion for normal and abnormal performance
      was 6.1ms for the mean gap detection threshold and 60% for the percentage of
      correct responses.

PMID- 21180944
TI  - Auditory processing, acoustic reflex and phonological expression.
AB  - It is thought that a close relationship exists between auditory processing, the
      acoustic reflex and speech. AIM: A retrospective study to evaluate these three
      aspects in children with and without phonological disorders and seek any
      relationship among them. MATERIAL METHODS: 46 children were enrolled: 24 had
      normal speech abilities and 22 had phonological disorders. All children underwent
      auditory processing and acoustic reflex threshold testing. DESIGN: Cross
      sectional contemporary. RESULTS: Auditory processing and acoustic reflex
      thresholds were abnormal in all children with phonological disorders. This was
      not the case in children with normal speech development. CONCLUSION: Changes in
      the auditory processing and acoustic reflex thresholds are closely related to
      speech difficulties.

PMID- 21180945
TI  - Evaluation of auditory processing and phonemic discrimination in children with
      normal and disordered phonological development.
AB  - Auditory processing and phonemic discrimination are essential for communication.
      TYPE OF STUDY: Retrospective. AIM: To evaluate auditory processing and phonemic
      discrimination in children with normal and disordered phonological development.
      MATERIAL AND METHODS: An evaluation of 46 children was carried out: 22 had
      phonological disorders and 24 had normally developing speech. Diotic , monotic
      and dichotic tests were applied to assess auditory processing and a test to
      evaluate phonemic discrimination abilities. DESIGN: Cross-sectional,
      contemporary. RESULTS: The values of normally-developing children were within the
      normal range in all auditory processing tests; these children attained maximum
      phonemic discrimination test scores. Children with phonological disorders
      performed worse in the latter, and presented disordered auditory processing.
      CONCLUSION: Auditory processing and phonemic discrimination in children with
      phonological disorders are altered.

PMID- 21180946
TI  - Quality of life in elderly with dizziness.
AB  - Dizziness is frequent in elderly people. AIMS: To evaluate the Quality of Life
      (QoL) in elderly subjects with dizziness, relate it with gender and age. MATERIAL
      AND METHOD: A prospective study comprising 120 elderly patients with dizziness
      evaluated with Brazilian versions of the Whoqol-bref and the dizziness handicap
      inventory (DHI). The factor analysis (FA), the Mann Whitney and Kruskal Wallis
      tests, and the Spearman correlation were applied to study the results. RESULTS:
      The most compromised domains were the DHI physical domain and the Whoqol-bref
      physical and environment domains. FA resulted in 3 factors in the DHI and 5
      factors in the Whoqol-bref. There was a moderate correlation (-0.596) in the
      total scores of both instruments. Males had a better QoL in the "environment
      perception and introspectivity" and "health perception" factors of the Whoqol
      bref test. Females had a better QoL in the "functionality perception" factor of
      the Whoqol-bref test. There were no significant age differences. CONCLUSIONS:
      Elderly patients with dizziness have a worse QoL. Elderly females with dizziness
      have worse QoL scores in "environment perception and introspectivity" and "health
      perception" and better QoL in the "functionality perception" factor compared to
      elderly males.

PMID- 21180947
TI  - Polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene and risk of head
      and neck squamous cell carcinoma.
AB  - Methylenetetrahydrofolate reductase gene (MTHFR) C677T polymorphism may be a risk
      factor for head and neck squamous cell carcinoma due to changes in folate levels
      that can induce disorders in the methylation pathway, which results in
      carcinogenesis. AIM: To evaluate MTHFR C677T polymorphism in patients with head
      and neck squamous cell carcinoma and in individuals with no history of cancer,
      and to assess the association of this disease with clinical histopathological
      parameters. SERIES AND METHODS: A retrospective study that assessed gender, age,
      tobacco, alcohol consumption and clinical histopathological parameters in 200
      patients (100 with disease and 100 with no history of cancer). PCR-RFLP molecular
      analysis was carried out and the chi-square test and multiple logistic regression
      were applied for the statistical analysis. RESULTS: There was no association
      between MTHFR C677T polymorphism and head and neck cancer (p = 0.50). Significant
      differences between the study and control groups were observed at age over 50
      years, tobacco use, and male gender (p <0.001). There was no association of
      disease with clinical-histopathological parameters. CONCLUSION: No association
      between the MTHFR C677T polymorphism and head and neck squamous cell carcinoma
      was possible in this study.

PMID- 21180948
TI  - Analysis of static postural balance using a 3d electromagnetic system.
AB  - Early detection of postural disorders is essential for timely interventions in
      patients with imbalance. AIM: A pilot study describing a new tool for evaluating
      static postural balance. STUDY DESIGN: A cross-sectional study of a contemporary
      series. MATERIAL AND METHOD: Twenty-five volunteers (15 women and 10 men) were
      evaluated. The mean age was 25.8 +/- 4.2 years, the mean weight was 63.9 +/-
      13.1Kg, the mean height was 1.68 +/- 0.08 m and the body mass index was 22.3+/
      3.3kg/m2. Posturography was done by analysing postural sway with an
      electromagnetic system; a sensor was attached to the skin over the spinous
      process of the first thoracic vertebra. Tests were carried out with the subjects
      in the orthostatic position for 90 seconds, with eyes opened(EO) and closed(EC)
      on stable and unstable surfaces. RESULTS: When the influence of the surface was
      analyzed (stable x unstable) in the EO condition, there were significant
      differences in the middle-lateral parameters (m-l) (p=0.004) and total path
      (p=0.01), and in the m-l (p=0.004) and total (p=0.014) speed. In the EC
      condition, there were significant differences in all parameters (p<0.001). The
      influence of the vision was observed in all parameters only on unstable surfaces
      (p<0.05). CONCLUSION: The new tool was efficient for analysing postural sway.

PMID- 21180949
TI  - Osteochondroplastic tracheobronchopathy: report on 02 cases and bibliographic
      review.
AB  - Osteochondroplastic tracheobronchopathy (OT) is a rare benign disorder of the
      lower part of the trachea and the upper part of the main bronchus characterized
      by numerous submucosal calcified nodules, sessile, cartilaginous and/or osseous
      with laryngotracheobronchial lumen projection. There are less than 400 cases
      reported in the word literature. AIM: to report and discuss 02 cases of OT with a
      bibliography review. MATERIALS AND METHODS: we report on 02 cases with
      bibliography revision from MEDLINE, LILACS and PUBMED data. STUDY DESIGN:
      observational, descriptive, case reports. CONCLUSION: the symptoms result from
      airway obstruction, causing dry cough, dyspnea and recurrent respiratory tract
      infections. The diagnostic hypothesis is established by endoscopy of the upper
      airway (laryngo-tracheo-bronchoscopy), and the trachea/chest computed tomography
      is the best image exam to define tracheal nodule alterations. The differential
      diagnoses are papillomatosis, amyloidosis and sarcoidosis chondrosarcoma
      hamartoma and calcified paratracheal lymph nodes. There is no specific treatment
      and the prognosis is good. Surgery is restricted to moderate or severe airway
      obstructions. Otorhinolaryngologists must include OT in the differential
      diagnosis of cases of upper airway and tracheobronchial tree suggestive symptoms.

PMID- 21180950
TI  - Johanson-Blizzard syndrome.

PMID- 21180951
TI  - Rosai-Dorfman disease as a differential diagnosis in vocal cord ulceration.

PMID- 21180952
TI  - Foreign body in the tonsillary region as a complication of tonsillectomy.

PMID- 21180953
TI  - Malignant lymphoepithelioma of the submandibular gland: a rare entity.

PMID- 21180956
TI  - A novel bioactive glass-ceramic for treating dentin hypersensitivity.
AB  - Dentin hypersensitivity (DH) is a painful response to stimulus applied to the
      open dentinal tubules of a vital tooth. It's a common oral condition, however,
      without an ideal treatment available yet. This work evaluated in vitro the effect
      of micron-sized particles from a novel bioactive glass-ceramic (Biosilicate) in
      occluding open dentinal tubules. A dentin disc model was employed to observe
      comparatively, using scanning electron microscopy (SEM), dentinal tubule
      occlusion by different products and deposition of hydroxyl carbonate apatite
      (HCA) on dentin surface by Biosilicate, after a single application: G1 -
      Dentifrice with potassium nitrate and fluoride; G2 - Two-step calcium phosphate
      precipitation treatment; G3 - Water-free gel containing Biosilicate particles
      (1%); G4 - Biosilicate particles mixed with distilled water in a 1:10 ratio; all
      of them after 1, 12 and 24 hours of immersion in artificial saliva. Fourier
      transform infrared spectroscopy (FTIR) was performed to detect HCA formation on
      dentin discs filled with Biosilicate after 2 minutes, 30 minutes and 12 hours of
      immersion in artificial saliva. SEM showed a layer of HCA formed on dentin
      surface after 24 hours by G4. G1, G2 and G3 promoted not total occlusion of open
      dentinal tubules after 24 hours. FTIR showed HCA precipitation on the dentin
      surface induced by Biosilicate after 30 minutes. The micron-sized particles from
      the bioactive glass-ceramic thus were able to induce HCA deposition in open
      dentinal tubules in vitro. This finding suggests that Biosilicate may provide a
      new option for treating DH.

PMID- 21180957
TI  - Effect of different frequencies of fluoride dentifrice and mouthrinse
      administration: an in situ study.
AB  - The effect of a combination of topical fluoridation methods for inhibition of
      enamel demineralization in the face of a cariogenic challenge has not been
      clearly established. This in situ crossover study aimed to assess whether the
      addition of daily use of fluoride mouthrinse (FR) to that of fluoride dentifrice
      (FD) is equivalent to increasing the frequency of FD application in terms of the
      effect on enamel demineralization and fluoride content. Over 3 phases of 14 days
      each, 12 volunteers wore appliances containing enamel blocks exposed to a 20 %
      sucrose solution 8 times/day. During each phase the blocks underwent one of the
      following treatments: 2x/day FD, 2x/day FD + 1x/day FR, and 3x/day FD. The blocks
      were assessed for hardness and fluoride content. Three x/day FD did not differ
      from 2x/day + 1x/day FR, however it enhanced demineralization protection when
      compared to 2x/day FD. All treatments produced an increase in enamel fluoride
      content compared to no treatment (sound blocks) (p < 0.05), but the differences
      between them were not significant. The results of this study suggest that the
      daily use of fluoride mouthrinse combined with that of fluoride dentifrice has
      similar effects on enamel demineralization and fluoride content when compared to
      increasing the frequency of fluoride dentifrice use.

PMID- 21180958
TI  - Accuracy of three electronic apex locators in the presence of different
      irrigating solutions.
AB  - The present study compared the accuracy of three electronic apex locators (EALs) 
      Elements Diagnostic(r), Root ZX(r) and Apex DSP(r) - in the presence of
      different irrigating solutions (0.9% saline solution and 1% sodium hypochlorite).
      The electronic measurements were carried out by three examiners, using twenty
      extracted human permanent maxillary central incisors. A size 10 K file was
      introduced into the root canals until reaching the 0.0 mark, and was subsequently
      retracted to the 1.0 mark. The gold standard (GS) measurement was obtained by
      combining visual and radiographic methods, and was set 1 mm short of the apical
      foramen. Electronic length values closer to the GS (+/- 0.5 mm) were considered
      as accurate measures. Intraclass correlation coefficients (ICCs) were used to
      verify inter-examiner agreement. The comparison among the EALs was performed
      using the McNemar and Kruskal-Wallis tests (p < 0.05). The ICCs were generally
      high, ranging from 0.8859 to 0.9657. Similar results were observed for the
      percentage of electronic measurements closer to the GS obtained with the Elements
      Diagnostic(r) and the Root ZX(r) EALs (p > 0.05), independent of the irrigating
      solutions used. The measurements taken with these two EALs were more accurate
      than those taken with Apex DSP(r), regardless of the irrigating solution used (p
      < 0.05). It was concluded that Elements Diagnostic(r) and Root ZX(r) apex
      locators are able to locate the cementum-dentine junction more precisely than
      Apex DSP(r). The presence of irrigating solutions does not interfere with the
      performance of the EALs.

PMID- 21180959
TI  - Evaluation of bone ingrowth into porous titanium implant: histomorphometric
      analysis in rabbits.
AB  - A porous material for bone ingrowth with adequate pore structure and appropriate
      mechanical properties has long been sought as the ideal bone-implant interface.
      This study aimed to assess in vivo the influence of three types of porous
      titanium implant on the new bone ingrowth. The implants were produced by means of
      a powder metallurgy technique with different porosities and pore sizes: Group 1 =
      30 % and 180 um; Group 2 = 30% and 300 um; and Group 3 = 40% and 180 um;. Six
      rabbits received one implant of each type in the right and left tibiae and were
      sacrificed 8 weeks after surgery for histological and histomorphometric analyses.
      Histological analysis confirmed new bone in contact with the implant, formed in
      direction of pores. Histomorphometric evaluation demonstrated that the new bone
      formation was statistically significantly lower in the group G1 than in group G3,
      (P = 0.023). Based on these results, increased porosity and pore size were
      concluded to have a positive effect on the amount of bone ingrowth.

PMID- 21180961
TI  - Susceptibility of planktonic cultures of Streptococcus mutans to photodynamic
      therapy with a light-emitting diode.
AB  - The objective of this study was to evaluate the effect of photodynamic therapy
      with erythrosine and rose bengal using a light-emitting diode (LED) on planktonic
      cultures of S. mutans. Ten S. mutans strains, including nine clinical strains and
      one reference strain (ATCC 35688), were used. Suspensions containing 106 cells/mL
      were prepared for each strain and were tested under different experimental
      conditions: a) LED irradiation in the presence of rose bengal as a
      photosensitizer (RB+L+); b) LED irradiation in the presence of erythrosine as a
      photosensitizer (E+L+); c) LED irradiation only (P-L+); d) treatment with rose
      bengal only (RB+L-); e) treatment with erythrosine only (E+L-); and f) no LED
      irradiation or photosensitizer treatment, which served as a control group (P-L-).
      After treatment, the strains were seeded onto BHI agar for determination of the
      number of colony-forming units (CFU/mL). The results were submitted to analysis
      of variance and the Tukey test (p <= 0.05). The number of CFU/mL was
      significantly lower in the groups submitted to photodynamic therapy (RB+L+ and
      E+L+) compared to control (P-L-), with a reduction of 6.86 log10 in the RB+L+
      group and of 5.16 log10 in the E+L+ group. Photodynamic therapy with rose bengal
      and erythrosine exerted an antimicrobial effect on all S. mutans strains studied.

PMID- 21180960
TI  - Inhibitory activity of root canal irrigants against Candida albicans,
      Enterococcus faecalis and Staphylococcus aureus.
AB  - The present study evaluated the antimicrobial activity of three root canal
      irrigants against Enterococcus faecalis, Candida albicans, and Staphylococcus
      aureus. These microorganisms were incubated in the presence of citric acid (6 and
      10%), EDTA (17%), and NaOCl (0.5, 1.0, 2.5, and 5.25%). Agar diffusion tests were
      performed and redox indicator resazurin was used to evaluate the inhibitory
      effect of the irrigants on the metabolic activity of these microorganisms. The
      mean diameters of the inhibition zones for the C. albicans cultures were 11.6 mm
      (17% EDTA), 5.5 mm (0.5% NaOCl), 12.9 mm (1% NaOCl), 22.1 mm (2.5% NaOCl), and
      28.5 mm (5.25% NaOCl). The mean diameters of the inhibition zones for E. faecalis
      were 2.8 mm (1% NaOCl), 5.4 mm (2.5% NaOCl), and 8.3 mm (5.25% NaOCl). For S.
      aureus, the mean values were 8.0 mm (17% EDTA), 3.0 mm (1% NaOCl), 8.8 mm (2.5%
      NaOCl), and 10.0 mm (5.25% NaOCl). Most of the irrigant solutions presented
      effective antimicrobial activity against C. albicans. A high inhibitory effect on
      the metabolic activity of E. faecalis was detected when the microorganisms were
      incubated with 17% EDTA. The same result was reached when S. aureus was incubated
      in the presence of > 2.5% NaOCl. Altogether, these results indicate that 2.5% and
      5.25% NaOCl are microbicides against S. aureus while 0.5% and 1% NaOCl are only
      microbiostatic against the tested bacteria. The 6% and 10% citric acid as well as
      17% EDTA did not affect the viability of any of the assayed microorganisms.

PMID- 21180963
TI  - Association between overbite and craniofacial growth pattern.
AB  - The purpose of the present study was to assess the association between overbite
      and craniofacial growth pattern. The sample comprised eighty-six cephalograms
      obtained during the orthodontic pretreatment phase and analyzed using the
      Radiocef program to identify the craniofacial landmarks and perform orthodontic
      measurements. The variables utilized were overbite, the Jarabak percentage and
      the Vert index, as well as classifications resulting from the interpretation of
      these measurements. In all the statistical tests, a significance level of 5% was
      considered. Measurement reliability was checked by calculating method error.
      Weighted Kappa analysis showed that agreement between the facial types defined by
      the Vert index and the direction of growth trend established by the Jarabak
      percentage was not satisfactory. Owing to this lack of equivalency, a potential
      association between overbite and craniofacial growth pattern was evaluated using
      the chi-square test, considering the two methods separately. No relationship of
      dependence between overbite and craniofacial growth pattern was revealed by the
      results obtained. Therefore, it can be concluded that the classification of
      facial growth pattern will not be the same when considering the Jarabak and the
      Ricketts anayses, and that increased overbite cannot be associated with a
      braquifacial growth pattern, nor can openbite be associated with a dolichofacial
      growth pattern.

PMID- 21180962
TI  - Relationship among malocclusion, number of occlusal pairs and mastication.
AB  - This study evaluated the relationship among malocclusion, number of occlusal
      pairs, masticatory performance, masticatory time and masticatory ability in
      completely dentate subjects. Eighty healthy subjects (mean age = 19.40 +/- 4.14
      years) were grouped according to malocclusion diagnosis (n = 16): Class I, Class
      Class II-2, Class III and Normocclusion (control). Number of occlusal pairs was
      determined clinically. Masticatory performance was evaluated by the sieving
      method, and the time used for the comminute test food was registered as the
      masticatory time. Masticatory ability was measured by a dichotomic self
      perception questionnaire. Statistical analysis was done by one-way ANOVA, ANOVA
      on ranks, Chi-Square and Spearman tests. Class II-1 and III malocclusion groups
      presented a smaller number of occlusal pairs than Normocclusion (p < 0.0001),
      Class I (p < 0.001) and II-2 (p < 0.0001) malocclusion groups. Class I, and III
      malocclusion groups showed lower masticatory performance values compared to
      Normocclusion (p < 0.05) and Class II-2 (p < 0.05) malocclusion groups. There
      were no differences in masticatory time (p = 0.156) and ability (chi2 = 3.58/p=
      0.465) among groups. Occlusal pairs were associated with malocclusion (rho =
      0.444/p < 0.0001) and masticatory performance (rho = 0.393/p < 0.0001), but
      malocclusion was not correlated with masticatory performance (rho = 0.116/p=
      0.306). In conclusion, masticatory performance and ability were not related to
      malocclusion, and subjects with Class I, II-1 and III malocclusions presented
      lower masticatory performance because of their smaller number of occlusal pairs.

PMID- 21180964
TI  - Determining skeletal maturation stage using cervical vertebrae: evaluation of
      three diagnostic methods.
AB  - The aim of the present study was to compare the use of three cervical vertebral
      evaluation methods (Hassel-Farman, Baccetti et al., and Seedat-Forsberg) for
      determinating skeletal maturation stage in orthodontic patients. Twenty-three
      radiographs were randomly selected from a private orthodontic practice. Each
      radiograph was analyzed on three separate occasions by four evaluators (one
      radiologist and three orthodontists), who determined the skeletal maturation
      stage using the references established by each of the three methods.
      Intraevaluator and interevaluator comparisons were performed, and the degree of
      agreement was established using the weighted Kappa coefficient (95% CI). Good
      agreement (Kappa between 0.61 and 0.80) was observed between the determinations
      of most of the evaluators. The three methods demonstrated clinical applicability.
      However, the method proposed by Baccetti et al. achieved the best results,
      followed by the Hassel-Farman and the Seedat-Forsberg methods.

PMID- 21180965
TI  - Metallographic analysis of the internal microstructure of orthodontic mini
      implants.
AB  - Effective orthodontic anchorage may be obtained by miniimplants inserted into the
      maxillary bones. However, the risk of miniimplant failure is one of the most
      important issues, especially the rupture of its structure referred to as
      fracture, mainly due to metal deficiencies. This study analyzed the internal
      microstructure of orthodontic mini-implants, ascertaining the composition of the
      metal to detect possible discontinuities from the surface to the core of the
      screws. Eighteen samples of mini-implants, of 3 different brands, were obtained.
      The samples were cold-embedded in methyl methacrylate polymer, and were sectioned
      both longitudinally (3 samples of each brand) and transversely (the other 3
      screws of each brand). After preparation, the samples were observed using a light
      microscope at up to 2,000 x magnification. The results showed that the mini
      implants thus analyzed were composed of an Alpha-Beta globular phase of titanium
      alloy, patterns A1 and A9 (in accordance with the "Technical Committee of
      European Titanium Producers"). The miniimplants did not present any defects such
      as bubbles, imperfections or fissures, in either longitudinal or transverse
      sections, in their internal microstructure. All samples met the requirements of
      international norms. Orthodontists must be aware of the metal composition and
      internal microstructure of mini-implants, to decrease the risk of fractures.

PMID- 21180966
TI  - Comparison of different methods involved in the planning of clinical crown
      lengthening surgery.
AB  - There is little material in the literature that compares biological width
      measurements in periapical and bite-wings radiographs with clinical measurements.
      The purpose of this study was to compare measurements of biological width taken
      by three different methods which are frequently used for planning periodontal
      surgery - periapical radiograph, bite-wing radiograph and transperiodontal
      probing - with the trans-surgical measurements. Thirty-four sites from twenty-one
      subjects were analyzed. The intra-class correlation coefficients between
      measurements obtained trans-surgically (gold standard) and those obtained by
      transperiodontal probing, periapical radiography and bite-wing radiography were
      determined. Average measurements were compared using the Wilcoxon test at a
      significance level of 0.05. Also, the frequency distribution of differences
      between test measurements and the gold standard was calculated. The results
      showed that transperiodontal probing (mean 2.05 mm) was the most accurate
      measurement, as compared to the gold standard (mean 1.97 mm), with no
      statistically significant difference observed. On the other hand, periapical and
      bite-wing radiographic mean values (1.56 mm and 1.72 mm, respectively) were
      smaller than the gold standard, with statistically significant differences (p <
      0.05). It was concluded that transperiodontal probing was the most accurate
      measurement, as compared to the gold standard, followed by that obtained with the
      bite-wing radiograph. The clinical relevance of these results could be that
      planning for crown lengthening surgery should, preferably, include
      transperiodontal probing.

PMID- 21180967
TI  - Effect of non-surgical periodontal treatment on chronic kidney disease patients.
AB  - Chronic kidney disease (CKD) is a debilitating systemic condition. Our working
      hypothesis is that CKD predialysis patients with periodontitis would respond
      poorly to periodontal treatment owing to immunologic compromise. Twenty-one
      predialysis patients (group 1) and 19 individuals without clinical evidence of
      kidney disease (group 2) with chronic periodontitis were subjected to non
      surgical periodontal treatment with no antibiotics. Clinical periodontal and
      systemic parameters were evaluated at baseline and 3 months after treatment. Both
      groups showed significant and similar post-treatment improvements in all
      periodontal parameters examined. Most interestingly, periodontal treatment had a
      statistically significant positive effect on the glomerular filtration rate of
      each individual (group 1, p = 0.04; group 2, p = 0.002). Our results indicate
      that chronic periodontitis in predialysis kidney disease patients improved
      similarly in patients with chronic periodontitis and no history of CKD after
      receiving non-surgical periodontal therapy. This study demonstrates that CKD
      predialysis patients show a good response to non-surgical periodontal treatment.

PMID- 21180968
TI  - Methodological model of chronic stress associated with ligature-induced
      periodontitis in rats: a radiographic study.
AB  - This study evaluated the time efficiency of stress associated with ligature
      induced periodontitis in rats. Sixty adult Wistar rats, housed in temperature
      controlled rooms and receiving water and food ad libitum, were randomly separated
      into stress (n = 30) or control groups (n = 30). All animals were anesthetized,
      and nylon ligatures were placed at the gingival margin level of the maxillary
      right second molars. After the induction of periodontitis, rats in the stress
      group were subjected to physical restraint for 12 hours daily. The animals were
      euthanized after 7, 15 and 30 days by anesthetic overdose (10 animals per group
      per period). The right hemimaxillae were stored in formalin solution for 48
      hours. Parallel radiographic images of the hemimaxillae were taken and processed
      following standard procedures. Radiographic examination was performed by a
      blinded and previously calibrated investigator. Bone height level was measured,
      and data were submitted to analysis of variance and post hoc Bonferroni tests (p
      < 0.05). Rats in the stress group had greater bone loss than those in the control
      group at 7 and 15 days post-induction (p < 0.05). After 30 days, there was no
      statistically significant difference between the groups (p > 0.05). Restraint
      stress modulates the short-term progression of periodontal disease in rats.
      Therefore, the 12-hour daily physical restraint stress model in rats applied for
      up to 15 days is suitable for the investigation of the combined effect of
      ligation and restraint stress on periodontal degradation.

PMID- 21180969
TI  - In vitro effect of low intensity laser on the cytotoxicity produced by substances
      released by bleaching gel.
AB  - This in vitro study aimed to analyze the effect of different parameters of
      phototherapy with low intensity laser on the viability of human dental pulp
      fibroblasts under the effect of substances released by bleaching gel. Cells were
      seeded into 96 wells plates (1 x 103 cells/well) and placed in contact with
      culture medium conditioned by a 35 % hydrogen peroxide bleaching gel for 40
      minutes, simulating the clinical condition of the in-office bleaching treatment.
      Cells cultured in ideal growth conditions served as positive control group (PC),
      and the cells grown in conditioned medium and non-irradiated served as negative
      control group (NC). Cells grown in conditioned medium were submitted to a single
      irradiation with a diode laser (40 mW, 0.04 cm2) emitting at visible red (660 nm;
      RL) or near infrared (780 nm; NIR) using punctual technique, in contact mode and
      energy densities of 4, 6 or 10 J/cm2. The cell viability was analyzed through the
      MTT reduction assay immediately and 24 hours after the irradiation. The data was
      compared by ANOVA followed by the Tukey's test (p <= 0.05). The cell viability
      increased significantly in 24 hours within each group. The PC presented cell
      viability significantly higher than NC in both experimental times. Only the
      NIR/10 J/cm2 group presented cell viability similar to that of PC in 24 hours.
      The phototherapy with low intensity laser in defined parameters is able to
      compensate the cytotoxic effects of substances released by 35 % hydrogen peroxide
      bleaching gel.

PMID- 21180970
TI  - Assessment of simulated mandibular condyle bone lesions by cone beam computed
      tomography.
AB  - There are many limitations to image acquisition, using conventional radiography,
      of the temporomandibular joint (TMJ) region. The Computed Tomography (CT) scan is
      a better option, due to its higher accuracy, for purposes of diagnosis, surgical
      planning and treatment of bone injuries. The aim of the present study was to
      analyze two protocols of cone beam computed tomography for the evaluation of
      simulated mandibular condyle bone lesions. Spherical lesions were simulated in 30
      dry mandibular condyles, using dentist drills and drill bits sizes 1, 3 and 6.
      Each of the mandibular condyles was submitted to cone beam computed tomography
      (CBCT) using two protocols: 1) axial, coronal and sagittal multiplanar
      reconstruction (MPR); and 2) sagittal plus coronal slices throughout the
      longitudinal axis of the mandibular condyles. For these protocols, 2 observers
      analyzed the CBCT images independently, regarding the presence or not of
      injuries. Only one of the observers, however, performed on 2 different occasions.
      The results were compared to the gold standard, evaluating the percentage of
      agreement, degree of accuracy of CBCT protocols and observers' examination. The z
      test was used for the statistical analysis. The results showed there were no
      statistically significant differences between the 2 protocols. There was greater
      difficulty in the assessment of small-size simulated lesions (drill # 1). From
      the results of this study, it can be concluded that CBCT is an accurate tool for
      analyzing mandibular condyle bone lesions, with the MPR protocol showing slightly
      better results than the sagittal plus coronal slices throughout the longitudinal
      axis.

PMID- 21180971
TI  - Influence of the photoinitiator system and light photoactivation units on the
      degree of conversion of dental composites.
AB  - The aim of this study was to observe the influence of two light polymerization
      units (LED or halogen light) on the degree of conversion (DC) of three dental
      composites with lighter shades and a different photoinitiator system. The top (T)
      and bottom (B) surfaces of 60 discs of composite resin (FiltekTM Supreme,
      FiltekTM Z250, TetricTM Ceram Bleach) cured either by LED or by halogen lamp (HL)
      were studied using an FT-Raman spectrometer. The degree of conversion (DC) was
      evaluated by following the changes in the intensity of the methacrylate C=C
      stretching mode at 1640 cm-1. The calculated DC ranged from 54.2% (B) to 73.4%
      (T) and from 60.2% (B) to 76.6% (T) for the LED and HL, respectively. LED and
      halogen devices were able to produce an adequate DC for all the resins tested.

PMID- 21180972
TI  - Where and how are Brazilian dental students using Glass lonomer Cement?
AB  - Glass Ionomer Cements (GICs) have a wide range of uses in Dentistry, and the
      manipulation technique used can influence the results obtained. This study aimed
      at assessing the knowledge held by Dental School students from a city in Southern
      Brazil regarding the use of GIC, and the clinical technique chosen for its use
      and its applications. A structured questionnaire was applied to 60 advanced
      dental students. Descriptive statistics was used to analyze the quantitative
      data. All students had already used the material. Regarding the purpose for which
      the material was used, all students (100%) had used it as a dental cavity liner,
      83.3% had used it as a temporary restorative material after endodontic treatment,
      and 73.3% had used it as a permanent restoration in primary teeth. Regarding the
      clinical technique used, 86.7% said that they insert the material while it still
      has a shiny surface, 33% said that they finish and polish the restoration in a
      following session, and only 28.3% said that they apply a surface protection
      immediately after the restoration is placed. Although students generally seem to
      be acquainted with the fundamental knowledge and main techniques involved in GIC
      use, they occasionally fail to follow all the technical steps required during
      clinical application, which may affect treatment outcome. Therefore, professors
      should stress that all the clinical procedures required during GIC application
      must be followed strictly to improve the performance of this material.

PMID- 21180973
TI  - Methodological advances in population studies of food and nutrition.

PMID- 21180974
TI  - [International cooperation: initiatives in graduate studies in public health].

PMID- 21180975
TI  - Recommendations for folate intake in women: implications for public health
      strategies.
AB  - Folate deficiency has been associated with anemia and other adverse outcomes in
      pregnancy such as neural tube defects. The current recommendations for prevention
      of such outcomes are difficult to achieve through diet only, and folic acid
      supplementation and food fortification are feasible public health strategies.
      However, it is necessary to determine the usual diet and supplement use among
      women of reproductive age, including an accurate assessment of other dietary
      micronutrients. In addition to the beneficial effects observed in randomized
      clinical trials, health risks to the population have also been widely evaluated
      and discussed in the scientific community: for a minority to benefit from
      fortification programs, many are exposed to high folic acid intake levels.

PMID- 21180976
TI  - Applying the triads method in the validation of dietary intake using biomarkers.
AB  - The triads method is applied in validation studies of dietary intake to evaluate
      the correlation between three measurements (food frequency questionnaire,
      reference method and biomarker) and the true intake using validity coefficients
      (A). The main advantage of this technique is the inclusion of the biomarker,
      which presents independent errors compared with those of the traditional methods.
      The method assumes the linearity between the three measurements and the true
      intake and independence between the three measurement errors. Limitations of this
      technique include the occurrence of rho > 1, known as "Heywood case", and the
      existence of negative correlations, which do not allow the calculation of A. The
      objective of this review is to present the concept of the method, describe its
      application and examine the validation studies of dietary intake that use the
      triads method. We also conceptualize the "bootstrap" method, used to estimate the
      confidence intervals of the validity coefficients.

PMID- 21180977
TI  - A new classification of foods based on the extent and purpose of their
      processing.
AB  - This paper describes a new food classification which assigns foodstuffs according
      to the extent and purpose of the industrial processing applied to them. Three
      main groups are defined: unprocessed or minimally processed foods (group 1),
      processed culinary and food industry ingredients (group 2), and ultra-processed
      food products (group 3). The use of this classification is illustrated by
      applying it to data collected in the Brazilian Household Budget Survey which was
      conducted in 2002/2003 through a probabilistic sample of 48,470 Brazilian
      households. The average daily food availability was 1,792 kcal/person being 42.5%
      from group 1 (mostly rice and beans and meat and milk), 37.5% from group 2
      (mostly vegetable oils, sugar, and flours), and 20% from group 3 (mostly breads,
      biscuits, sweets, soft drinks, and sausages). The share of group 3 foods
      increased with income, and represented almost one third of all calories in higher
      income households. The impact of the replacement of group 1 foods and group 2
      ingredients by group 3 products on the overall quality of the diet, eating
      patterns and health is discussed.

PMID- 21180978
TI  - Dietary recommendations: comparing dietary guidelines from Brazil and the United
      States.
AB  - The Brazilian dietary guidelines are based in part on mainstream United States'
      recommendations, in spite of the criticisms and shortcomings of the American
      guidelines. In this paper, Brazilian food guidelines are summarized and discussed
      in comparison with the USA recommendations. American and Brazilian dietary
      recommendations are quite similar in many aspects, particularly those related to
      variety in the diet, the importance of physical activity and weight management.
      Different to American guidelines, those from Brazil advise people to choose fresh
      foods, to prefer healthier types of fat, to limit trans fat intake and to eat
      good sources of protein, but does not recommend the consumption of whole grains.
      Besides the challenges related to their implementation, indicators for the
      evaluation of the effectiveness of these guidelines should be established from
      the beginning, particularly those related to changes in dietary habits and the
      prevalence of obesity.

PMID- 21180979
TI  - Assessing the validity of a food frequency questionnaire among low-income women
      in Sao Paulo, southeastern Brazil.
AB  - This study describes the validity of a food frequency questionnaire (FFQ) in 93
      low-income women (20-65 years), participating in a case-control study in Sao
      Paulo, Brazil. Two FFQ (FFQ1 and FFQ2, 12 months apart) and three 24-hour dietary
      recalls (24hR) were conducted between 2003 and 2004 to estimate dietary intake
      during the past year. The Pearson correlation coefficients (crude, energy
      adjusted and de-attenuated) were used for comparisons between FFQ and 24hR. The
      agreement between the methods was further examined by the Bland-Altman analysis.
      For the assessment of long-term reliability, the energy-adjusted intra-class
      correlation coefficients were mostly around 0.40, but higher for vitamin A and
      folate (0.50-0.56). Energy-adjusted, attenuation-corrected Pearson validity
      correlations between FFQ and DR ranged from 0.30-0.54 for macronutrients to 0.20
      0.48 for micronutrients, with higher value for calcium (0.75). There were small
      proportions of grossly misclassified nutrient intakes, while Bland-Altman plots
      indicated that the FFQ is accurate in assessing nutrient intake at a group level.

PMID- 21180980
TI  - Development and validation of a food frequency questionnaire (FFQ-Porto Alegre)
      for adolescent, adult and elderly populations from Southern Brazil.
AB  - This study assessed the validity of a food frequency questionnaire (FFQ-Porto
      Alegre), covering 135 food items, in comparison with the average of two
      consecutive 24-hour dietary recall questionnaires for adolescents, adults, and
      elderly who were randomly selected from a population-based survey. The Pearson
      correlation coefficients and cross-classification by quartiles of intake were
      used. The nutrients were log transformed and energy adjusted. The mean of
      adjusted de-attenuated correlation coefficient for adolescents was 0.44 and
      ranged from 0.18 (zinc) to 0.69 (folate) and for adult and elderly participants
      they were, respectively, 0.42, ranging from 0.16 (iron) to 0.73 (energy) and
      0.52, ranging from 0.25 (vitamin E) to 0.84 (energy). The average classification
      percentage into the same or adjacent quartile for the two methods was 74.6% for
      adolescents, 74.9% for adults, and 81.2% for the elderly population. The FFQ
      showed fair relative validity for adolescents and adults, and may be used to
      study the dietary determinants of obesity and non-transmissible diseases in
      epidemiological surveys.

PMID- 21180981
TI  - Dietary assessment in the 1993 Pelotas (Brazil) birth cohort study: comparing
      energy intake with energy expenditure.
AB  - The study aims to describe and compare two methods of energy intake assessment
      and one measure of energy expenditure applied in adolescents from a birth cohort.
      In a sub-sample of the 1993 Pelotas (Brazil) birth cohort, followed up in 2006-7,
      information on intake was obtained through a food-frequency questionnaire (FFQ)
      and three 24-hour-recalls (24hR), while energy expenditure was assessed using an
      accelerometer. Bland & Altman plots were used in the analyses in order to compare
      the methods. The mean difference between FFQ and 24hR was 592 +/- 929cal/day.
      Compared to energy expenditure, intake was overestimated when measured by FFQ
      (357 +/- 968cal/day) and underestimated by 24hR (-278 +/- 714cal/day). In spite
      of the great differences between energy intake obtained using the two methods,
      lower differences were observed when these methods were compared to expenditure.

PMID- 21180982
TI  - Validation of a food frequency questionnaire to assess the consumption of
      carotenoids, fruits and vegetables among adolescents: the method of triads.
AB  - The aim of this study was to validate the intake of carotenoids, fruits and
      vegetables estimated by the Food Frequency Questionnaire for Adolescents (FFQA)
      using the method of triads. Blood samples were collected from 80 elementary
      school adolescents to assess serum levels of beta-carotene. Partial correlation
      coefficients (r) were calculated between an estimated intake of carotenoids,
      fruits and vegetables and the serum levels of beta-carotene. Validity
      coefficients were calculated using the method of triads. With the exception of
      carotenoids, partial r from the food frequency questionnaire (FFQ) were greater
      than those of the 24-hour recall (24hR). The fruit/vegetable group showed the
      highest partial r for the FFQ (r = 0.235) and the 24hR (r = 0.137). The highest
      validity coefficient was obtained for the vegetable group, as assessed by the FFQ
      (r = 0.873). On average, the validity coefficient values for the FFQ were greater
      than those obtained for the 24hR or the beta-carotene serum levels. The FFQA is
      an accurate tool for estimating the intake of carotenoids, fruits and vegetables
      in this population group.

PMID- 21180983
TI  - How many 24-hour recalls or food records are required to estimate usual energy
      and nutrient intake?
AB  - For dietary intake assessments, one needs to know the minimum 24-hour recall or
      food record replications that are required to estimate usual energy and nutrient
      intake and to classify subjects correctly according to their nutrient intake.
      Data from two different studies on dietary intake that were carried out with 300
      adults and 169 adolescents in the Rio de Janeiro Metropolitan area, Brazil, were
      analyzed. To estimate the number of replications two methods were applied: one
      based on the variances ratio, the other based on the within-subject variance
      alone. The most important results found were the requirement for 14 replications
      for boys and men, 15 for girls, and 23 for women in order to estimate energy
      intake with a precision of 90%. Also four replications for boys and seven for
      men, girls and women are required to classify individuals' energy intake with a
      correlation coefficient of 0.9. Due to the within variance in food intake, a
      larger number of replications is required to obtain estimates of usual intakes
      than is needed to classify subjects according to levels of dietary intake.

PMID- 21180984
TI  - Assessment of protein intake during pregnancy using a food frequency
      questionnaire and the effect on postpartum body weight variation.
AB  - The aim of this study was to investigate the effect of protein intake during
      pregnancy on postpartum weight variation. This was a prospective cohort study
      with 421 women interviewed at 15 days (baseline) and 2, 6, and 9 months
      postpartum. Data on diet were obtained using the food frequency questionnaire,
      focusing on the second and third trimesters. Protein intake was considered
      adequate when women consumed >= 1.2g of protein per kg body weight, and
      inadequate when < 1.2g/kg. The study adopted the mixed effects model for repeated
      measurements over time. The results showed a mean postpartum weight loss of
      0.409kg/month (+/-0.12) (p < 0.01). Women with adequate protein intake during
      pregnancy lost an additional 0.094kg/month (+/-0.04) during postpartum (p = 0.03)
      when compared to women with inadequate intake. The model was adjusted for energy,
      % body fat, stature, age, schooling, skin color, and smoking. Recommended protein
      intake during pregnancy favored postpartum weight reduction.

PMID- 21180985
TI  - Diet quality index adjusted for energy requirements in adults.
AB  - This study aimed to develop a diet quality index (DQI-a) adjusted for energy
      requirement. Dietary intake of adults was assessed using 24-hour food recall. The
      DQI was developed for scores evenly distributed across ten items characterizing
      different aspects of diet: food groups, nutrients, and variety. The components
      categorized under the food groups from the Dietary Guide for Brazilians were
      adjusted according to the estimated energy requirements of the population
      studied. Index consistency and correlation with nutrients of the diet was
      analyzed by Cronbach's alpha. A total of 737 individuals were assessed and energy
      requirements ranged from 1,800 to 2,500kcal among women and 2,500 to 3,400kcal in
      men. The food group with greatest variation in total portions was cereals and
      tubers. Cronbach's alpha of the DQI-a was 0.643 and the index correlated with
      most of the nutrients. The DQI-a can be considered a valuable instrument for
      assessing diet quality of the Brazilian population.

PMID- 21180986
TI  - Sources of variation of energy and nutrient intake among adolescents in Sao
      Paulo, Brazil.
AB  - The aim of the current study was to describe the sources of variation of energy
      and nutrient intake and to calculate the number of repetitions of diet
      measurements to estimate usual intake in adolescents from Sao Paulo, Brazil. Data
      was collected using 24-hour dietary recalls (24hR) in 273 adolescents between
      2007 and 2008. Individuals completed a repeat 24hR around two months later. The
      sources of variation were estimated using the random effect model. Variance
      ratios (within-person to between-person variance ratio) and the number of
      repetitions of 24hR to estimate usual intake were calculated. The principal
      source of variation was due to within-person variance. The contribution of day of
      week and month of year was less than 8%. Variations ranged from 1.15 for calcium
      to 7.31 for vitamin E. The number of 24hR repeats required to estimate usual
      intake varied according to nutrient and gender, numbering 15 for males and 8 for
      females.

PMID- 21180987
TI  - A comparison of three statistical methods applied in the identification of eating
      patterns.
AB  - This work aimed to compare the results of three statistical methods applied in
      the identification of dietary patterns. Data from 1,009 adults between the ages
      of 20 and 65 (339 males and 670 females) were collected in a population-based
      cross-sectional survey in the Metropolitan Region of Rio de Janeiro, Brazil.
      Information on food consumption was obtained using a semi-quantitative food
      frequency questionnaire. A factor analysis, cluster analysis, and reduced rank
      regression (RRR) analysis were applied to identify dietary patterns. The patterns
      identified by the three methods were similar. The factor analysis identified
      "mixed", "Western", and "traditional" eating patterns and explained 35% of the
      data variance. The cluster analysis identified "mixed" and "traditional"
      patterns. In the RRR, the consumption of carbohydrates and lipids were included
      as response variables and again "mixed" and "traditional" patterns were
      identified. Studies comparing these methods can help to inform decisions as to
      which procedures best suit a specific research scenario.

PMID- 21180988
TI  - Focused Principal Component Analysis: a graphical method for exploring dietary
      patterns.
AB  - The aim of the present study was to introduce Focused Principal Component
      Analysis (FPCA) as a novel exploratory method for providing insight into dietary
      patterns that emerge based on a given characteristic of the sample. To
      demonstrate the use of FPCA, we used a database of 1,968 adults. Food intake was
      obtained using a food frequency questionnaire covering 26 food items. The focus
      variables used for analysis were age, income, and schooling. All analyses were
      carried out using R software. The graphs generated show evidence of socioeconomic
      inequities in dietary patterns. Intake of whole-wheat foods, fruit, and
      vegetables was positively correlated with income and schooling, whereas for
      refined cereals, animal fats (lard), and white bread this correlation was
      negative. Age was inversely associated with intake of fast-food and processed
      foods and directly associated with a pattern that included fruit, green salads,
      and other vegetables. In an easy and direct fashion, FPCA allowed us to visualize
      dietary patterns based on a given focus variable.

PMID- 21180989
TI  - Assessing food dietary intakes in Japanese-Brazilians using factor analysis.
AB  - We describe the use of factor analysis for assessing food habits in Japanese
      Brazilians. Dietary data from 1,283 participants of a cross-sectional study were
      used. Besides statistical criteria, we also used the conceptual meaning of
      identified profiles to obtain scores for dietary patterns (Japanese or Western
      profile). Paired Student t test, linear regression and Poisson models were used
      to verify the existence of relationship between these scores and generation, body
      mass index (BMI), waist circumference and presence of metabolic syndrome,
      respectively. First generation subjects had higher mean Japanese profile scores
      and lower Western profile scores than those of second generation. The Western
      dietary pattern was associated with BMI (p = 0.001), waist circumference (p =
      0.023) and metabolic syndrome (p < 0.05). We concluded that these scores were
      able to discriminate subjects who maintained their traditional Japanese lifestyle
      or otherwise, and that the incorporation of a Western lifestyle is associated to
      high values of BMI, waist circumference and presence of metabolic syndrome.

PMID- 21180990
TI  - Discrepancies among ecological, household, and individual data on fruits and
      vegetables consumption in Brazil.
AB  - Information on fruits and vegetables consumption in Brazil in the three levels of
      dietary data was analyzed and compared. Data about national supply came from Food
      Balance Sheets compiled by the FAO; household availability information was
      obtained from the Brazilian National Household Budget Survey (HBS); and actual
      intake information came from a large individual dietary intake survey that was
      representative of the adult population of Sao Paulo city. All sources of
      information were collected between 2002 and 2003. A subset of the HBS,
      representative of Sao Paulo city, was used in our analysis in order to improve
      the quality of the comparison with actual intake data. The ratio of national
      supply to household availability of fruits and vegetables was 2.6 while the ratio
      of national supply to actual intake was 4.0. The discrepancy ratio in the
      comparison between household availability and actual intake was smaller, 1.6.
      While the use of supply and availability data has advantages, as lower cost, must
      be taken into account that these sources tend to overestimate actual intake of
      fruits and vegetables.

PMID- 21180991
TI  - Seasonal effect on nutrient intake in adults living in Southern Brazil.
AB  - The objective of this study was to investigate the effect of seasonality on
      nutrient intake in healthy adults from the southernmost metropolitan area of
      Brazil. The dietary intake (24-hour dietary recall on six different days) in a
      sample of 162 adults (114 women), aged 20 to 69, was obtained during the year
      2007. The nutrient intake was averaged for each season and adjusted for energy
      intake using the residual method. The effect of season on energy, macro and micro
      nutrient intake was investigated based on the Generalized Estimate Equations
      (GEE) model. There were statistically significant differences between seasons for
      carbohydrate and total fat intake after controlling for gender, age, education,
      and interactions. In summer carbohydrate intake was higher than other seasons
      while the total fat intake was lower. These findings highlight the importance of
      considering seasonal variations not only for evaluating dietary intake but also
      nutrition and public health policy recommendations, particularly in adult
      populations living in temperate regions.

PMID- 21180992
TI  - Per capita versus adult-equivalent estimates of calorie availability in household
      budget surveys.
AB  - This study aims to estimate an adult-equivalent scale for calorie requirements
      and to determine the differences between adult-equivalent and per capita
      measurements of calorie availability in the Brazilian population. The study used
      data from the 2002-2003 Brazilian Household Budget Survey. The calorie
      requirement for a reference adult individual was based on the mean requirements
      for adult males and females (2,550kcal/day). The conversion factors were defined
      as the ratios between the calorie requirements for each age group and gender and
      that of the reference adult. The adult-equivalent calorie availability levels
      were higher than the per capita levels, with the largest differences in rural and
      low-income households. Differences in household calorie availability varied from
      22kcal/day (households with adults and an adolescent) to 428kcal/day (households
      with elderly individuals), thus showing that per capital measurements can
      underestimate the real calorie availability, since they overlook differences in
      household composition.

PMID- 21180993
TI  - Development of a food frequency questionnaire in a probabilistic sample of adults
      from Niteroi, Rio de Janeiro, Brazil.
AB  - With the purpose of generating a list of foods for a food-frequency
      questionnaire, data from 24h dietary recalls on a typical day from a
      probabilistic sample of 1,724 adults of Niteroi, Rio de Janeiro, Brazil, were
      analyzed. The frequency of food intake, the total intake of energy and
      macronutrients and the relative contribution of each food item to total energy
      and macronutrient intake were calculated. The most frequently reported food items
      (> 50% of adults) were rice, coffee, beans, refined canesugar, and bread. Whole
      milk was consumed more frequently then skimmed milk or semi-skimmed milk. Beef
      was consumed by more adults than chicken, pork or fish. Approximately 90% of
      energy and macronutrients intake was explained by 65 food items. The list of food
      items generated in the present analysis is similar to those found in other
      samples of adults from urban areas in Brazil. It may be possible to generate a
      core list of common foods with addition of regional foods to be used nationally
      in urban areas of the country.

PMID- 21180994
TI  - Reverse approach: a new paradigm in the treatment of synchronous liver metastasis
      from colorectal cancer.

PMID- 21180996
TI  - Cox-2 and its association with prognostic factors and response to primary
      chemotherapy in patients with breast cancer.
AB  - OBJECTIVE: To evaluate the immunohistochemical expression of cox-2 before primary
      chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and its
      association with initial tumor size, lymph node status, hormone receptors,
      expression of HER2 and the clinical and pathological response in patients with
      breast cancer. METHODS: We conducted a retrospective study with 41 women with
      histopathological diagnosis of ductal breast carcinoma. They underwent primary
      chemotherapy with FEC regimen (5-fluorouracil, epirubicin and cyclophosphamide)
      at 500mg/m2, 75mg/m2 and 500 mg/m2, respectively. Inclusion criteria were age
      range between 30 and 70 years, stage II to IIIA, absence of metastasis, primary
      tumor of the breast, single, unilateral, with ductal invasion at histology and
      absence of heart disease and pregnancy. To evaluate the expression of HER2/neu
      protein we used rabbit monoclonal antibodies. To visualize the expression of cox
      2 protein we used polyclonal antibodies obtained from goats' serum. The
      evaluation of clinical response to treatment was performed during physical
      examination by measuring the major tumor axis with a pachymeter. Measurements
      were taken at admission and after primary chemotherapy cycles. After three
      chemotherapy sessions at intervals of 21 days the surgical procedure was carried
      out. We adopted the criteria of RECIST. After the operation we evaluated the
      local pathological response, which was considered complete when there was absence
      of invasive neoplasia and of the in situ component. In immunohistochemical
      assessing of estrogen receptors we used estrogen receptor NCL-ER6F11 and, for
      progesterone, progesterone receptor NCL-PGR-312, considering positive the
      staining of 10% or more tumor cells. RESULTS: The distribution according to UICC
      clinical stage classified six patients in stage IIA (14.6%), 22 in stage IIB
      (53.6%) and 13 stage IIIA (31.8%). The initial clinical evaluation of the major
      tumor axis ranged from 2.5 to 15 cm and a median of 5 cm. We identified 14
      patients (34.1%) with negative lymph node status, and 27 positive (65.9%). It was
      observed that 19 (46.3%) were in premenopause and 22 (53.6%) in menopause.
      CONCLUSION: There was an association of the expression of Cox-2 to the factors
      associated with poor prognosis in breast cancer, such as positive lymph node
      status, negative hormone receptors and HER2 expression.

PMID- 21180995
TI  - Cytophotometric expression of Caspase-3 in papillary thyroid carcinoma in nodular
      goiter colloid.
AB  - OBJECTIVE: To describe quantitative cytophotometric expression of the marker
      caspase-3 in colloid goiter and in papillary carcinoma of the thyroid, comparing
      the immunoexpression between them. METHODS: An immunohistochemistry study has
      been made on the protein caspase-3 in 17 of paraffin blocks of papillary
      carcinoma of the thyroid and 20 cases of colloid goiter, using SAMBA 4000 (r)
      (System of Microscopic Analysis of Automatic Search), aiming analysis of the two
      variables: marker index and optical density. RESULTS: Statistic analysis
      indicated a significant difference for marker index between colloid goiter and
      papillary carcinoma, being this difference larger in the carcinoma. Significant
      difference in optical density hasn't been found. For colloid goiter, the
      estimated correlation coefficient between the marker index and optical density
      was 0,72, indicating the rejection of the null hypothesis (p <0,001), affirming
      that positive and significant association exists between them. For the papillary
      carcinoma of the thyroid, the same correlation was 0,34 and so, it is not
      possible to affirm that there's an association between them. CONCLUSION: For
      colloid goiter there is a positive and significant association between the two
      variables - marker index and optical density -, while for the papillary
      carcinoma, this is not proved. The quantitative analysis for caspase-3
      demonstrates that apoptosis is larger in the papillary carcinoma of the thyroid
      than in colloid goiter.

PMID- 21180997
TI  - Multidisciplinary approach to morbidly obese patients undergoing surgical
      treatment by adjustable gastric banding.
AB  - OBJECTIVE: To evaluate the outcome of the surgical treatment of morbidly obese
      patients by Adjustable Gastric Banding (ABG) followed in a multidisciplinary
      clinic. METHODS: We studied 20 patients with BMI ranging from 36.6 to 72 kg/m2 (X
      = 47.51 + / - 6.1) and aged between 36 to 60 years, undergoing placement of AGB.
      Preoperative comorbidities were hypertension (nine), type II diabetes (four),
      severe sleep apnea (one), hypertriglyceridemia (four) and severe orthopedic
      problems (three). In the post-operative period patients were followed at a
      multidisciplinary clinic (surgeon, endocrinologist, psychiatrist and
      nutritionist). In the first six months, the orientation was of monthly visits for
      band adjustments and nutritional counseling. After six months the visits occurred
      every two or three months, as needed. RESULTS: The operative time ranged from 40
      to 180 minutes; hospital stay varied from one to ten days (X = 36 hours). Two
      patients required surgical reintervention for late complications: a rotation of
      the portal and a band superior slippage. Follow-up ranged from 28 to 36 months.
      The average weight loss was 29.26 kg +/- 8.8, or 24.37% +/- 6.1 of the original
      weight and 49.16% +/- 11.3 overweight. The average BMI ranged from 47.51 to
      34.88. There was global improvement of comorbidities, markedly in the patients
      with greater weight loss. CONCLUSION: The results were satisfactory for most
      patients on the variables weight loss and improvement of comorbidities.

PMID- 21180998
TI  - Evaluation of the cytokines IL-10 and IL-13 as mediators in the progression of
      Symmers fibrosis in patients with hepatosplenic schistosomiasis mansoni.
AB  - OBJECTIVE: To investigate the serum levels of IL-10 and IL-13 in patients with
      hepatosplenic schistosomiasis mansoni (HSM), evaluating the role of these
      cytokines in the development of hepatic fibrosis. METHODS: The study was
      prospective and analytical, developed at the Department of Surgery, Federal
      University of Pernambuco, Keizo Asami Laboratory of Immunology. We studied three
      groups: Group I - 25 patients with hepatosplenic schistosomiasis mansoni who were
      not submitted to surgery; Group II - 30 individuals who underwent splenectomy and
      ligature of left gastric vein; Group III - 33 subjects without hepatosplenic
      schistosomiasis mansoni or any other disease or condition that could compromise
      the hepatic functional reserve. Serum concentrations of IL-10 and IL-13 were
      obtained through ELISA. Considering their non-parametric nature, all
      concentrations were analyzed by Kruskal-Wallis test, with p<0.05 used to reject
      the null hypothesis. RESULTS: The mean concentrations of IL-10 in ng/mL in serum
      were GI: 50.0 +/- 59.0; GII: 38.0 +/- 270; GIII: 38.0 +/- 20.0. Concentrations of
      IL-13 in ng/mL in the serum of patients were respectively: 41.0 +/- 93.0 in GI,
      16.0 +/- 17.0 in GII and 18.0 +/- 34.0 in GIII. There was no significant
      difference between the mean concentrations of IL-10 and IL-13 between the study
      groups (p> 0.05). CONCLUSION: The mean serum concentrations of IL-10 and IL-13
      were similar in all three groups, indicating that possibly the presence of these
      cytokines in serum is not associated with different degrees of Symmers fibrosis
      in patients with hepatosplenic schistosomiasis mansoni.

PMID- 21180999
TI  - Immunohistochemistry expression of tumor markers CD34 and P27 as a prognostic
      factor of clinically localized prostate adenocarcinoma after radical
      prostatectomy.
AB  - OBJECTIVE: to analyze the immunohistochemical expression of P27 and CD34 markers
      as prognostic factors in patients with localized prostate cancer. METHODS:
      analysis of 100 patients with localized prostate cancer submitted to curative
      surgery. We carried out the usual histological preparation, followed by
      immunohistochemistry to detect the accumulation of P27 and CD34 protein followed
      by statistical analysis. RESULTS: in the evaluation of P27 marker and on the
      correlation with the variables we found significant difference in Gleason score
      with positive expression (positive P27) related to lower mean PSA (p = 0.091),
      lower Gleason score (p < 0.0001) and smaller tumor area in CD34 (p = 0.036).
      Regarding the CD34 marker at the tumor area, it was observed that the smaller the
      positive CD34, the lower the PSA value (p < 0.0001) and lower the Gleason score
      (r = 0.5726, p < 0.0001), and the higher the positive CD34, the higher the
      staging (r = 0.3305, p <0.0001) and the chance of recurrence (p = 0.002).
      Patients with higher stage also displayed larger positive CD34 areas (p <
      0.0001). CONCLUSION: the markers CD34 and P27 are associated with events specific
      to prostate cancer, however, only CD34 was able to determine the possibility of
      biochemical recurrence.

PMID- 21181000
TI  - Laser treatment of venous malformations.
AB  - OBJECTIVE: To evaluate whether treatment of venous congenital vascular
      malformations with the use of laser technology provides lightening or
      disappearance of lesions with a high degree of satisfaction reported by patients
      and observed by the physician. METHODS: A retrospective study gathered 26
      patients suffering from vascular malformation, of which 73.07% were female and
      were treated with the PhotoDerm(r) device. The treatment of vascular
      malformations needed an average of 6.43 sessions, with intervals of six to eight
      weeks. Patients included in this study had skin type II (57.40%) and type III
      (42.30%), according to the Fitzpatric's classification. The mean age ranged from
      14 to 61 years, averaging 36.70 years. Data were obtained through the completion
      of an informed protocol by the patient. RESULTS: High satisfaction rates were
      reported (96.16%) and only one case (3.84%) was partially satisfied when
      considering lightening or disappearance of lesions. When evaluated by medical
      professionals, lesions disappeared in 80.76% and became lighter in 19.24%.
      CONCLUSION: The treatment of venous vascular malformations with Photo-Derm(r) is
      safe and effective as it offered a high degree of patient satisfaction and good
      results in the disappearance of the lesions.

PMID- 21181001
TI  - Effects of fatty acids on liver regeneration in rats.
AB  - OBJECTIVE: To study the effects of polyunsaturated fatty acids (PUFA) omega-3 and
      omega-6 in the oxidative stress and in liver regeneration in rats subjected to
      70% partial hepatectomy (PH, 70% hepatectomy, Higgins-Anderson partial
      hepatectomy). METHODS: 72 young male Wistar rats were randomly divided into four
      equal-sized groups: control (G1), partially hepatectomized (G2), partially
      hepatectomized with two weeks daily intraperitoneal infusion of omega-3 (G3) and
      partially hepatectomized with two weeks daily intraperitoneal infusion of omega-6
      (G4). In moments 36 h (T1), 168 h (T2) and 336 h (T3) post-PH, thiobarbituric
      acid reactive substances (TBARS) and reduced glutathione (GSH) were measured in
      plasma and liver tissue, while glucose and total bilirubin were measured in
      blood. The mass of the residual liver in the same moments was the parameter used
      to estimate the evolution of liver regeneration. RESULTS: omega-3 PUFA inhibited
      liver regeneration and induced reduction of hepatic GSH concentration seven days
      post-PH. Omega-6 PUFA, in contrast, showed no inhibitory effect on regeneration.
      There was an increase of lipid peroxidation both in blood and liver with
      administration of omega-6. CONCLUSION: Omega-3 PUFA retarded post-PH liver
      regeneration, probably through inhibition of oxidative stress. Omega-6 PUFA
      increased TBARS concentrations in blood and liver but did not alter the evolution
      of the liver regenerative process.

PMID- 21181002
TI  - Evaluation of topical metronidazole in the healing wounds process: an
      experimental study.
AB  - OBJECTIVE: To assess the efficacy of a topical 4% metronidazole solution in wound
      healing by secondary intention in rats. METHODS: We made circular wounds two
      inches in diameter at the back of rats and studied healing at 3, 7, 14 and 21
      days. The wound contraction and epithelialization were assessed by peripheral
      digital planimetry and myofibroblasts by immunohistochemistry with a-SMA.
      RESULTS: There was no difference between groups regarding wound contraction. In
      wounds treated with metronidazole peripheral epithelialization was evident early
      on day 3 (p <0.001) and there were no differences in other periods. In the
      control group, the number of myofibroblasts was higher on day 7 (p = 0.003) and
      day 14 (p = 0.001) and in the experimental group it was suggestively higher on
      day 3 (p = 0.06). CONCLUSION: Metronidazole 4% solution at a dose of 50 mg/kg
      applied topically to wounds healing by secondary intention facilitates early
      peripheral epithelialization, does not interfere with wound contraction and
      delays the appearance of myofibroblasts.

PMID- 21181003
TI  - Effectiveness of the combined use of lactic acid film and polypropylene mesh in
      the formation of intraperitoneal adhesions--an experimental model in rats.
AB  - OBJECTIVE: To evaluate the efficacy of a lactic acid biomaterial (SurgiWrap(r))
      as a protector of the polypropylene mesh (Marlex(r)) regarding the formation of
      intraperitoneal adhesions in rats. METHODS: Forty Wistar rats formed the
      following groups: Group 0 (Sham)--only laparotomy; Group I--polypropylene mesh;
      Group II--polypropylene mesh protected by a film of lactic acid. These animals
      were submitted to laparotomy and placement (or not) of the meshes at closing.
      After 21 days they were sacrificed for analysis of the adhesion type (0-3),
      percentage of affected area and strength needed to rupture. RESULTS: Group 0
      showed no intraperitoneal adhesions. Regarding classification, type 3 adhesions
      had the highest prevalence in both groups 1 and 2. As for the strength to break
      adhesions, Group 1 had an average of 1.58 N and Group 2, 1.23 N. The mesh was
      surrounded by adhesions in more than 50% of their surface area in 87% of Group 1
      subjects and in 84% of Group 2 individuals. Through different statistical methods
      we found that there was no significant difference between groups for both
      variables. CONCLUSION: The combined use of polypropylene mesh and lactic acid
      bioprotector showed similar results in relation to intraperitoneal adhesion
      formation when compared to the sole use of the same mesh.

PMID- 21181004
TI  - Hepatectomy preoperative planning.
AB  - Hepatectomy can comprise excision of peripheral tumors as well as major surgeries
      like trisegmentectomies or central resections. Patients can be healthy, have
      localized liver disease or possess a cirrhotic liver with high operative risk.
      The preoperative evaluation of the risk of postoperative liver failure is
      critical in determining the appropriate surgical procedure. The nature of liver
      disease, its severity and the operation to be performed should be considered for
      correct preparation. Liver resection should be evaluated in relation to residual
      parenchyma, especially in cirrhotic patients, subjects with portal hypertension
      and when large resections are needed. The surgeon should assess the rationale for
      the use of hepatic volumetry. Child-Pugh, MELD and retention of indocyanine green
      are measures for assessing liver function that can be used prior to hepatectomy.
      Extreme care should be taken regarding the possibility of infectious
      complications with high morbidity and mortality in the postoperative period.
      Several centers are developing liver surgery in the world, reducing the number of
      complications. The development of surgical technique, anesthesia, infectious
      diseases, oncology, intensive care, possible resection in patients deemed
      inoperable in the past, will deliver improved results in the future.

PMID- 21181005
TI  - New technique for dynamic closure of the abdominal wall.
AB  - Advances in care of trauma patients and severe abdominal infections are
      responsible for an increasing number of laparostomies. The management of this
      entity is complex and several techniques have been described for its treatment.
      Recently the concept of dynamic closure of the abdominal wall was introduced in
      the literature with high success rates. The objective of this report is to serve
      as a foreword for a new approach for the treatment of laparostomy developed at
      the University Hospital of the University of Sao Paulo. This is a simple and low
      cost method, easily performed by a general surgeon. The procedure was also used
      prophylactically as reinforcement in tight abdominal closures. It is described in
      detail as well as the results in the first patients. Although promising,
      refinements and further studies are needed to validate the technique.

PMID- 21181006
TI  - Extended external hemipelvectomy for sigmoid adenocarcinoma treatment.
AB  - Surgery is the most effective way of treating a locally advanced colorectal
      carcinoma and an extended en bloc resection is necessary to achieve the best
      overall survival rate. In this rare case, a multi-visceral resection was
      performed along with the entire lower left limb and left iliac bone for a sigmoid
      carcinoma. The T4N0M0 (B3) tumor involved the left iliac vessels, left pelvic
      wall, small bowel and both rectus muscles, besides presenting with a skin
      fistula. A Hartmann colostomy was also performed. Chemotherapy was interrupted
      because of toxicity. The patient is free of disease after 38 months. There are
      very few cases that describe an extended hemipelvectomy as part of a colorectal
      carcinoma treatment.

PMID- 21181007
TI  - Gastric trichobezoar: case report.
AB  - Bezoars are foreign bodies impacted in the digestive tract resulting of their
      ingestion and accumulation, involving mainly the stomach. The most common types
      are phytobezoars, containing vegetables, fiber and seed, and the trichobezoar,
      made of hair. The present case is the description of a 25-year-old female with
      nonspecific dyspeptic symptoms associated to intestinal habit change. The
      diagnosis was suggested by computerized tomography in association with clinical
      history--initially omitted by the patient--of trichophagia for 10 years.
      Treatment consisted of anterior gastrotomy and remotion of the bezoar.

PMID- 21181008
TI  - Predictors of adherence to influenza vaccination for healthcare workers from a
      teaching hospital: a study in the prepandemic era.
AB  - INTRODUCTION: Even before the 2009 pandemics, influenza in healthcare workers
      (HCW) was a known threat to patient safety, while Influenza vaccine coverage in
      the same group was generally low. Identification of predictors for HCW adherence
      to Influenza vaccination has challenged infection control committees. METHODS:
      Our group conducted a cross-sectional survey in December 2007, interviewing 125
      HCWs from a teaching hospital to identify adherence predictors for Influenza
      vaccination. The outcomes of interest were: A - adherence to the 2007 vaccination
      campaign; B - adherence to at least three yearly campaigns in the past five
      years. Demographic and professional data were assessed through univariate and
      multivariate analysis. RESULTS: Of the HCWs interviewed, 43.2% were vaccinated
      against Influenza in 2007. However, only 34.3% of HCWs working in healthcare for
      more than five years had adhered to at least three of the last five vaccination
      campaigns. Multivariate analysis showed that working in a pediatric unit (OR =
      7.35, 95%CI = 1.90-28.44, p = 0.004) and number of years in the job (OR = 1.32,
      95%CI = 1.00-1.74, p = 0.049) were significant predictors of adherence to the
      2007 campaign. Physicians returned the worst outcome performances in A (OR =
      0.40, 95%CI = 0.16-0.97, p = 0.04) and B (OR = 0.17, 95%CI = 0.05-0.60, p =
      0.006). CONCLUSIONS: Strategies to improve adherence to Influenza vaccination
      should focus on physicians and newly-recruited HCWs. New studies are required to
      assess the impact of the recent Influenza A pandemics on HCW-directed
      immunization policies.

PMID- 21181009
TI  - Decline in prevalence and asymmetric distribution of human T cell lymphotropic
      virus 1 and 2 in blood donors, State of Minas Gerais, Brazil, 1993 to 2007.
AB  - INTRODUCTION: Human T cell lymphotropic virus types 1 and 2 (HTLV-1/2) are
      endemic in Brazil and are screened for in transfusion services since 1993. This
      study evaluated the evolution of the prevalence of HTLV-1 and 2 in blood donors
      of the Hemominas Foundation from 1993 to 2007, and its geographical distribution
      in State of Minas Gerais, Brazil. METHODS: The Hemominas Foundation is a
      centralized blood center in Minas Gerais, Brazil. The sources of data were the
      Hemominas Foundation Technical Bulletin and files from the centralized
      serological laboratory. Donors were tested in the period using enzyme linked
      immuno sorbent assays (ELISA), followed by Western blot, when repeatedly
      reactive. The data were analyzed by EPIINFO 6.2 and TABWIN 3.5 softwares.
      RESULTS: The average seroprevalence in the period 1993-2007 was 0.1%. A steady
      decline occurred from 0.4% in 1993 to below 0.1% in 2002 and later, with a
      transient peak of 0.5% in 1994. HTLV reactivity distribution was asymmetrical in
      the state, with regions of higher prevalence, interspersed with low prevalence
      areas. Comparison of positive and negative donors verified that increasing age
      was proportional to virus positivity. Odds ratio for age ranged from 1.43 (30 to
      39 years-old) to 3.09 (50 to 65 years-old). Women had a greater chance of being
      positive (OR-1.64), as previously described. CONCLUSIONS: Possible explanations
      for HTLV-1/2 prevalence decline are the exclusion of positive donors from the
      donor pool, an increase in repeat donors and ELISA test improvement, with
      reduction in the number of false positive results.

PMID- 21181010
TI  - PCR detection of multiple human herpesvirus DNA in saliva from HIV-infected
      individuals in Teresina, State of Piaui, Brazil.
AB  - INTRODUCTION: Human herpesviruses are frequently associated with orofacial
      diseases in humans (HSV-1, EBV, CMV and HHV-8), some can also cause systemic
      disease (CMV and HHV-8). The transmission of these viruses occurs by contact with
      infected secretions, especially saliva. Human immunodeficiency virus infection is
      associated with an increased risk of HHVs and related diseases. METHODS: This
      work aimed to detect HSV-1, EBV, CMV and HHV-8 DNA in saliva of HIV-infected
      patients from Teresina, northeast Brazil, by PCR and compare these findings with
      age and sex matched HIV-seronegative individuals. RESULTS: No difference in
      prevalence was verified between HHV detection in the saliva of HIV-seropositive
      individuals and controls. The individual frequencies of these viruses in these
      two populations were different. HIV seropositivity correlated positively with the
      presence of CMV (OR: 18.2, p= 0.00032) and EBV (OR: 3.44, p= 0.0081). No
      association between CD4 counts and the prevalence of HHVs in the saliva was
      observed; however, a strong association was determined between seropositivity and
      the presence of multiple HHV DNAs in saliva (OR: 4.83, p = 0.0028). CONCLUSIONS:
      These findings suggest the asymptomatic salivary shedding of HHVs is a common
      event between HIV-seropositive and seronegative individuals from Teresina, Piaui,
      Brazil, and, especially for HIV-seropositive patients, saliva is a risk factor
      for the acquisition/transmission of multiple HHVs.

PMID- 21181011
TI  - Antituberculosis drug-induced hepatotoxicity: a comparison between patients with
      and without human immunodeficiency virus seropositivity.
AB  - INTRODUCTION: The prevalence and risk factors for rifampin, isoniazid and
      pyrazinamide hepatotoxicity were evaluated in HIV-infected subjects and controls.
      METHODS: Patients with tuberculosis (30 HIV positive and 132 HIV negative), aged
      between 18 and 80 years-old, admitted to hospital in Brazil, from 2005 to 2007,
      were selected for this investigation. Three definitions of hepatotoxicity were
      used: I) a 3-fold increase in the lower limit of normal for alanine
      aminotransferase (ALT); II) a 3-fold increase in the upper limit of normal (ULN)
      for ALT, and III) a 3-fold increase in the ULN for ALT plus a 2-fold increase in
      the ULN of total bilirubin. RESULTS: In groups with and without HIV infection the
      frequency of hepatotoxicity I was 77% and 46%, respectively (p < 0.01). Using
      hepatotoxicity II and III definitions no difference was observed in the
      occurrence of antituberculosis drug-induced hepatitis. Of the 17 patients with
      hepatotoxicity by definition III, 3 presented no side effects and treatment was
      well tolerated. In 8 (36.4%) out of 22, symptoms emerged and treatment was
      suspended. Alcohol abuse was related to hepatotoxicity only for definition I.
      CONCLUSIONS: Depending on the definition of drug-induced hepatitis, HIV infection
      may or may not be associated with hepatotoxicity. The impact that minor
      alterations in the definition had on the results was impressive. No death was
      related to drug-induced hepatotoxicity. The emergence of new symptoms after
      initiating antituberculosis therapy could not be attributed to hepatotoxicity in
      over one third of the cases.

PMID- 21181012
TI  - Antimicrobial use and incidence of multidrug-resistant Pseudomonas aeruginosa in
      a teaching hospital: an ecological approach.
AB  - INTRODUCTION: Multidrug-resistant Pseudomonas aeruginosa is a major threat in
      healthcare settings. The use of antimicrobials can influence the incidence of
      resistant strains by direct and indirect mechanisms. The latter can be addressed
      by ecological studies. METHODS: Our group attempted to analyze the relation
      between the use of antipseudomonal drugs and the incidence of MDR-PA among 18
      units from a 400-bed teaching hospital. The study had a retrospective, ecological
      design, comprising data from 2004 and 2005. Data on the use of four
      antimicrobials (amikacin, ciprofloxacin, ceftazidime and imipenem) were tested
      for correlation with the incidence of MDR-PA (defined as isolates resistant to
      the four antimicrobials of interest) in clinical cultures. Univariate and
      multivariate linear regression analyses were performed. RESULTS: Significant
      correlations were determined between use and resistance for all antimicrobials in
      the univariate analysis: amikacin (standardized correlation coefficient = 0.73, p
      = 0.001); ciprofloxacin (0.71, p = 0.001); ceftazidime (0.61, p = 0.007) and
      imipenem (0.87, p < 0.001). In multivariate analysis, only imipenem (0.67, p =
      0.01) was independently related to the incidence of multidrug-resistant strains.
      CONCLUSIONS: These findings share similarities with those reported in individual
      based observational studies, with possible implications for infection control.

PMID- 21181013
TI  - Nosocomial infections in a Brazilian neonatal intensive care unit: a 4-year
      surveillance study.
AB  - INTRODUCTION: Report the incidence of nosocomial infections, causative
      microorganisms, risk factors associated with and antimicrobial susceptibility
      pattern in the NICU of the Uberlandia University Hospital. METHODS: Data were
      collected through the National Healthcare Safety Network surveillance from
      January 2006 to December 2009. The patients were followed five times/week from
      their birth to their discharge or death. RESULTS: The study included 1,443
      patients, 209 of these developed NIs, totaling 293 NI episodes, principally
      bloodstream infections (203; 69.3%) and conjunctivitis (52; 17.7%). Device
      associated infection rates were as follows: 17.3 primary bloodstream infections
      per 1,000 central line-days and 3.2 pneumonias per 1000 ventilator-days. The
      mortality rate in neonates with NI was 11.9%. Mechanical ventilation, total
      parenteral nutrition, orogastric tube, previous antibiotic therapy, use of CVC
      and birth weight of 751-1,000g appeared to be associated with a significantly
      higher risk of NI (p < 0.05). In multiple logistic regression analysis for NI,
      mechanical ventilation and the use of CVC were independent risk factors (p <
      0.05). Coagulase- negative Staphylococcus (CoNS) (36.5%) and Staphylococcus
      aureus (23.6%) were the most common etiologic agents isolated from cultures. The
      incidences of oxacillin-resistant CoNS and S. aureus were 81.8% and 25.3%,
      respectively. CONCLUSIONS: Frequent surveillance was very important to evaluate
      the association of these well-known risk factors with NIs and causative
      organisms, assisting in drawing the attention of health care professionals to
      this potent cause of morbidity.

PMID- 21181014
TI  - Glomerulonephritis in schistosomiasis mansoni: a time to reappraise.
AB  - INTRODUCTION: The current prevalence of glomerulonephritis in patients with
      hepatosplenic schistosomiasis mansoni in Brazil was evaluated. METHODS: Sixty
      three patients (mean age 45.5 +/- 11 years) attending the outpatient infectious
      disease clinic of a University Hospital in Belo Horizonte, Brazil, from 2007 to
      2009, were consecutively examined and enrolled in the present investigation.
      Diagnosis of hepatosplenic schistosomiasis was based on epidemiological, clinical
      and parasitological data and imaging techniques. Eight patients, who presented
      >30 mg/day albuminuria, were submitted to percutaneous ultrasound guided renal
      biopsy. Kidney tissue fragments were examined under light, direct
      immunofluorescence and electron microscopy. RESULTS: All patients showed
      mesangial enlargement. In five, mesangial hypercellularity was observed and four
      presented duplication of the glomerular basement membrane. Areas of glomerular
      sclerosis were diagnosed in four. Deposits of immunoglobulin M and C3 were
      present in six samples; deposits of IgG in four, IgA in three and C1q in two
      samples. In all patients, immunoglobulin A was reported in the lumen of renal
      tubules. Deposits of kappa and lambda were observed in six samples. Electron
      microscopy revealed dense deposits in the glomerular tissue of three patients.
      Arterial hypertension, small esophageal varices, slight increases in serum
      creatinine and decreases in serum albumin were associated with glomerular
      disease. CONCLUSIONS: Renal disease associated with hepatosplenic schistosomiasis
      was verified in 12.7% of patients and type I membranoproliferative
      glomerulonephritis was observed in 50% of them. Schistosomal glomerulopathy still
      is an important problem in patients with hepatosplenic schistosomiasis in Brazil.

PMID- 21181015
TI  - Dynamics of Capillaria-hepatica-induced hepatic septal fibrosis in rats.
AB  - INTRODUCTION: The pathogenesis of septal hepatic fibrosis, induced in rats by
      Capillaria hepatica infection, was studied with the aid of a large collection of
      stored paraffin blocks, representative of the different evolutive phases of
      fibrosis which appeared in 100% of infected rats. METHODS: Studies were conducted
      involving histology, immunohistochemistry, immunofluorescence and morphometric
      methods, in order to observe the dynamic behavior of the cellular and matrix
      components of fibrosis, over a one year period of evolution. RESULTS: Observation
      verified that septal fibrosis originates from several portal spaces
      simultaneously. Its origin and progression involve blood vessel proliferation
      (angiogenesis), multiplication of actin-positive cells (pericytes and
      myofibroblasts) and progressive collagen deposition. By the end of 4-5 months, a
      progressive decrease in all these components was observed, when signs of
      regression of septal fibrosis became more evident over time. CONCLUSIONS: Besides
      indicating the fundamental role played by angiogenesis in the pathogenesis of
      fibrosis, these morphological data concerning the dynamics of this C. hepatica
      experimental model proved to be adequate for future investigations regarding the
      functional aspects of fibrosis induction, progression and regression.

PMID- 21181016
TI  - Evaluation of an enzyme immunoassay for clinical diagnosis of neurocysticercosis
      in symptomatic patients.
AB  - INTRODUCTION: Neurocysticercosis is an infection of the human central nervous
      system caused by the metacestode larvae of Taenia solium. Neurocysticercosis is
      the most common parasitic disease in developing countries. Epilepsy is the most
      common clinical manifestation. Difficulties in confirming the diagnosis motivated
      the evaluation of the enzyme-linked immunosorbent assay on cerebral spinal fluid
      (CSF). METHODS: Twenty-two patients with NCC and 44 control patients were
      studied. CSF was analyzed using a commercial ELISA kit developed for NCC.
      Sensitivity and specificity were measured and a multivariate logistic regression
      was performed. RESULTS: Sensitivity and specificity of ELISA were 31.8% and 100%,
      respectively, with accuracy of 77.3%. Only the size of the lesions proved to be
      important for performance of the test. CONCLUSIONS: The results showed that ELISA
      contributes to the diagnosis of neurocysticercosis if the result is negative or
      if the patient has a lesion of 2 cm or more.

PMID- 21181017
TI  - Pulmonary paracoccidioidomycosis: radiology and clinical-epidemiological
      evaluation.
AB  - INTRODUCTION: The purpose of this study was to compare respiratory signs and
      symptoms between patients with and without chest X-ray abnormalities in order to
      establish the meaning of radiographic findings in pulmonary PCM diagnosis.
      METHODS: The epidemiological, clinical and radiological lung findings of 44
      patients with paracoccidioidomycosis (PCM) were evaluated. Patients were divided
      into two groups of 23 and 21 individuals according to the presence (group 1) or
      absence (group 2) of chest X-ray abnormalities, respectively, and their clinical
      data was analyzed with the aid of statistical tools. RESULTS: As a general rule,
      patients were rural workers, young adult males and smokers - group 1 and 2,
      respectively: males (91.3% and 66.7%); mean age (44.4 and 27.9 year-old); smoking
      (34.7% and 71.4 %); acute/subacute presentation (38.1% and 21.7%); chronic
      presentation (61.9% and 78.3%). The most frequent respiratory manifestations were
      - group 1 and 2, respectively: cough (25% and 11.4%) and dyspnea (22.7% and
      6.8%). No statistical difference was observed in pulmonary signs and symptoms
      between patients with or without radiographic abnormalities. The most frequent
      radiological finding was nodular (23.8%) or nodular-fibrous (19%), bilateral
      (90.5%) and diffuse infiltrates (85.7%). CONCLUSIONS: Absence of statistical
      difference in pulmonary signs and symptoms between these two groups of patients
      with PCM indicates clinical-radiological dissociation. A simplified
      classification of radiological lung PCM findings is suggested, based on
      correlation of these data and current literature review.

PMID- 21181018
TI  - Comparison of Bothropoides jararaca bites with and without envenoming treated at
      the Vital Brazil Hospital of the Butantan Institute, State of Sao Paulo, Brazil.
AB  - INTRODUCTION: This study analyses the cases of all bites (including dry bites)
      caused by Bothropoides jararaca attended at the Vital Brazil Hospital of the
      Butantan Institute, State of Sao Paulo, Brazil. METHODS: A retrospective study
      was conducted of patients bitten by Bothropoides jararaca (n=792) from January
      1990 to December 2004. The characteristics of the snake specimen, data related to
      the accident and clinical manifestations on admission were obtained from patient
      medical records. RESULTS: The majority of the cases in this study were caused by
      female and juvenile snakes. No stomach contents were found in 93.4% of the snake
      specimens after dissection. No statistical difference was observed between the
      occurrence of dry bites and the maturity or sex of the snake. The median SVL of
      snakes in mild and moderate cases was 40.5 cm and in severe cases, SVL increased
      to 99 cm. Necrosis was more common in the digits of the feet and hands (4.8%)
      compared to the other body regions (1.8%). A significant difference was verified
      between severity and a time interval greater than six hours from the bite to
      hospital admission. A significant association was verified between gingival
      bleeding and abnormal blood coagulability. In accidents caused by adult snakes,
      necrosis was more frequent (7.2%) compared to accidents caused by juvenile snakes
      (1%). CONCLUSIONS: In this work, the association between certain epidemiological
      data and the evolution of biological parameters in the clinical course of
      Bothrops sensu latu accidents were highlighted, contributing to the improvement
      of snake bite assistance.

PMID- 21181019
TI  - Accidents caused by Bothrops and Bothropoides in the State of Paraiba:
      epidemiological and clinical aspects.
AB  - INTRODUCTION: Bothrops and Bothropoides snakes cause 70% of the ophidic accidents
      in Brazil. The species that cause ophidic accidents in State of Paraiba are
      Bothropoides erythromelas, Bothrops leucurus and Bothropoides neuwiedi. METHODS:
      This is a prospective and transverse study, following a quantitative approach of
      accidents involving Bothrops and Bothropoides admitted to the Toxicological
      Assistance and Information Centers of Campina Grande and Joao Pessoa (Ceatox-CG
      and Ceatox-JP), aimed at identifying the epidemiological and clinical profile of
      such accidents. All of the patients admitted had medical diagnoses and were
      monitored at Ceatox-CG or Ceatox-JP. RESULTS: The genera Bothrops and
      Bothropoides caused 91.7% of the ophidic accidents reported. Snake bites were
      frequent in men (75.1%), rural workers (65.1%), literate individuals (69%)
      between 11 and 20 years-old (21.7%), and toes the most common area attacked
      (52.7%). Most (86.6%) patients were admitted within 6 hours after the
      accident/bite, with a predominance of mild cases (64.6%). The annual occurrence
      in Paraiba was 5.5 accidents/100,000 inhabitants and lethality was 0.2%.
      CONCLUSIONS: Positive changes in the profiles of these accidents were verified,
      such as the non-application of inadequate solutions, including the use of
      tourniquet, coffee grounds, garlic, suction and/or cutting the bitten area.
      Moreover, the Itinerant Laboratory project, linked to Paraiba State University in
      partnership with Ceatox-CG, has contributed positively, providing several cities
      of the state with information regarding the prevention of accidents involving
      venomous animals. The local press has also contributed, reporting the educational
      work developed by the centers.

PMID- 21181020
TI  - [HTLV-1 associated myelopathy: clinical and epidemiological profile in a 10-year
      case series study].
AB  - INTRODUCTION: Human T cell lymphotropic virus type 1 (HTLV-I) myelopathy
      (HAM/TSP) is a progressive disabling disorder. This work aimed to analyze
      clinical features and epidemiology in a sample of HAM/TSP. METHODS: All HTLV-1
      infected patients with diagnostic criteria for HAM/TSP, consecutively admitted to
      the Sarah Hospital from 1998 to 2007, were included in the study. RESULTS: 206
      patients (67% females; mean age: 53.8 years-old) were diagnosed with HAM/TSP. The
      mean time of evolution was 9.0 years. The most common neurological symptoms were
      chronic progressive spastic paraparesis, spasticity, pain, neurogenic bladder and
      neurogenic bowel. The neurological findings were hyperreflexia, Babinsky, Hoffman
      and peripheral neuropathy. Pain, spasticity and spinal cord atrophy, observed in
      MRI, were associated with time of disease (p<0.05). CONCLUSIONS: HAM/TSP is a
      very disabling disorder, in which pain is reported early, while spasticity and
      thoracic spinal cord atrophy appear in a later phase of the disease. Cases of
      HAM/TSP exist with a probable vertical viral transmission.

PMID- 21181021
TI  - [Mycological aspects and susceptibility in vitro the yeast of the genus Candida
      from HIV-positive patients in the State of Mato Grosso].
AB  - INTRODUCTION: Candidiasis is one of the most common fungal infections among
      patients infected by human immunodeficiency virus. The present study aimed to
      characterize yeasts of the genus Candida from distinct clinical samples from HIV
      positive patients and determine the in vitro susceptibility profile to five
      antifungal drugs. METHODS: Characterization of Candida sp was achieved using the
      classic methodology: biochemical (zymogram and auxanogram) and micromorphology
      (germinative tube growth test and slide microculture) tests. Genotypic technique
      (PCR) and identification by the commercial method API 20C AUX (Biomerieux) were
      also performed. To determine the in vitro susceptibility profile, five antifungal
      drugs were used (ketoconazole, fluconazole, itraconazole, voriconazole and
      amphotericin-B) following a commercially available method, the Etest. RESULTS:
      The procedure isolated 105 yeasts of the genus Candida from 102 HIV-infected
      patients. Of these, 82 (78.1%) were characterized as Candida albicans, 8 (7.6%)
      as C. parapsilosi s, 8 (7.6%) C. tropicalis, 4 (3.8%) C. krusei, 2 (1.9%) C.
      glabrata, and 1 (1%) as C. guiilliermondii. CONCLUSIONS: Considering the general
      profile of sensitivity, 60% of isolates were susceptible to all the antifungal
      drugs tested; however, the species C. tropicalis and C. krusei showed a tendency
      toward higher MICs to azoles than those obtained for C. albicans, suggesting
      resistance.

PMID- 21181022
TI  - [Evaluation of APRI score in liver disease following the introduction of
      antiretroviral therapy in HIV and HCV coinfected versus HIV monoinfected
      patients].
AB  - INTRODUCTION: The impact of highly active antiretroviral therapy (HAART) on
      hepatic fibrosis progression in HIV and hepatitis C virus coinfected patients is
      not completely understood. Noninvasive hepatic fibrosis markers show great
      promise in determining liver fibrosis staging and monitoring disease progression.
      METHODS: Twenty-four patients divided equally into two groups: 12 HIV
      monoinfected and 12 with HIV/HCV coinfected patients, were followed from July
      2008 to August 2009, after initiating HAART, with clinical, epidemiological and
      laboratorial assessments every 3 months and calculation of the aspartate
      aminotransferase to platelet ratio index (APRI). This study aimed to compare the
      progression of APRI, a noninvasive hepatic fibrosis marker, among populations
      with HIV and HIV/HCV coinfection. RESULTS: No differences were observed between
      the groups regarding age, sex, measurement of CD4 and HIV viral load in all
      consultations, type of HAART and APRI before initiating HAART. Coinfected
      patients showed a significantly higher APRI than the monoinfected group in month
      3 (0.57 +/- 0.31 x 0.27 +/- 0.105, p = 0.02) and 6 (0.93 +/- 0.79 x 0.28 +/-
      0.11, p = 0.04). CONCLUSIONS: In the present study, HAART was associated with
      APRI increases over six months follow-up in HIV/HCV coinfected patients,
      suggesting that these may be experiencing cumulative hepatotoxicity and immune
      reconstitution inflammatory syndrome after initiating antiretroviral drugs.

PMID- 21181023
TI  - [Bacterial contamination on platelet concentrates: identification, antimicrobial
      susceptibility profile and transfusion-related sepsis].
AB  - INTRODUCTION: Bacterial sepsis associated with the transfusion of platelet
      concentrates (PCs) results in serious clinical implications for patients. Given
      these implications, certain procedures have been integrated into the preparation
      and quality control of blood components to reduce the risk of bacterial
      contamination. This article describes the prevalence of bacterial contamination
      on transfused PCs, the bacterial spectrum detected and their antimicrobial
      susceptibility profile and transfusion reactions in receptors. METHODS: A total
      of 292 PCs (278 random and 14 per apheresis) from the Blood Center of the State
      of Rio Grande do Sul (HEMORGS), located in the city of Santa Maria, were tested.
      Quantities of 100 MUL and 200 MUL were collected from platelet bag tubing and
      seeded using two methodologies. RESULTS: Using the qualitative methodology,
      bacteria were isolated in five units (1.7%; 5/292), while only one was isolated
      using the quantitative methodology. Staphylococcus epidermidis was the
      microorganism identified in all samples. Two patients died of transfusion-related
      sepsis. CONCLUSIONS: Bacterial contamination due to PC transfusion is considered
      a major public health problem due to its association with high rates of morbidity
      and mortality. In this study only gram-positive microorganisms were isolated and
      none of the samples obtained by apheresis presented contamination.

PMID- 21181024
TI  - [Oxacillin-resistant coagulase-negative Staphylococci bacteremia at a teaching
      hospital in Santa Maria, State of Rio Grande do Sul, Brazil].
AB  - INTRODUCTION: This study aimed to characterize the prevalence and susceptibility
      profile to oxacillin-resistant Coagulase-negative Staphylococci strains isolated
      from blood cultures in a teaching hospital, located in Santa Maria, RS. In
      addition, different methodologies for phenotypic characterization of mecA
      mediated oxacillin resistance were compared with genotypic reference testing.
      METHODS: After identification (MicroScan - Siemens), the isolates were tested for
      antimicrobial sensitivity using disk diffusion and automation (MicroScan -
      Siemens). The presence of mecA gene was identified by the polymerase chain
      reaction molecular technique. RESULTS: The most common species was Staphylococcus
      epidermidis (n=40, 67%). The mecA gene was detected in 54 (90%) strains, while
      analysis of the sensitivity profiles revealed a high rate of resistance to
      multiple classes of antimicrobial drugs. However, all isolates were uniformly
      sensitive to vancomycin and tigecycline. The cefoxitin disk was the phenotypic
      method that best correlated with the gold standard. CONCLUSIONS: Analysis of the
      clinical significance of CoNS isolated from hemocultures and the precise
      detection of oxacillin resistance represent decisive factors for the correct
      choice of antibiotic therapy. Although vancomycin constitutes the normal
      treatment in most Brazilian hospitals, reduction in its use is recommended.

PMID- 21181025
TI  - [Leprosy in Buriticupu, State of Maranhao: active search for cases in the adult
      population].
AB  - INTRODUCTION: This study aimed to analyze the leprosy situation, focusing on the
      adult population of the town of Buriticupu, State of Maranhao. METHODS: An active
      search was conducted to identify new cases from 2005 to 2007. All patients with
      injuries suggestive of leprosy were submitted to cutaneous bacilloscopy and
      biopsies were performed when defining the clinical presentation was difficulty.
      RESULTS: 15,409 individuals participated in the study and 62 were diagnosed with
      leprosy which represents a detection coefficient of 40.23/10,000. Bacilloscopy
      showed positive results in six patients. The predominant clinical form was
      tuberculoid, 31 cases, followed by the indeterminate form (20 cases), the
      dimorphous form (10 cases) and the lepromatous form (1 case). The study also
      identified other skin diseases, including pityriasis versicolor, scabies,
      mycosis, vitiligo and carcinoma. CONCLUSIONS: The high detection coefficient
      defines the town of Buriticupu, MA, as hyperendemic for leprosy. Active cases
      search is an important method for disease control.

PMID- 21181026
TI  - [Evaluation years in leprosy patients treated with single dose alternative scheme
      ROM (rifampin, ofloxacin, minocycline), after seven to nine].
AB  - INTRODUCTION: In 1997, after obtaining a combined multi-state double-blind
      randomly controlled clinical trial study from nine Indian centers involved in the
      treatment of Hansen's Disease, the Ministry of Health adapted the single dose ROM
      Therapy approach in those cases involving the treatment of a single skin lesion,
      paucibacillary leprosy without evidence of peripheral nerve trunk involvement and
      indication of negative baciloscope, in the Referral Centers in Brazil. The study
      aimed to evaluate the effectiveness of the single dose ROM Therapy approach in
      those patients who were treated from the period of 1997 to 1999 in the Ambulatory
      Dermatologic Unit in the Hospital in Vitoria, ES. METHODS: Fifty-four patients
      with tuberculoid and indeterminate leprosy were selected and treated with the
      single dose ROM Therapy approach. These patients were contacted from March 2006
      up and until October 2006 for further clinical reevaluation. RESULTS: From the
      studies conducted, the following results were found to exist: 29 patients (85,2%;
      95%CI: 70-100,4) were cured, 5 patients (14,7%; 95%CI: 7,4-22,0) relapsed, and 20
      patients didn't return; however, there are no additional records of any
      notification of other treatment(s) in the State Department of Health's
      informational data banks. CONCLUSIONS: The study demonstrated a rate of cure of
      90.8% and a rate of relapse of 9.2% after a period of seven to nine years using
      the single dose ROM Therapy approach. Additionally, this alternative treatment
      further demonstrated a better effectiveness for a single skin lesion smaller than
      four centimeters and with an appearance in less than five years.

PMID- 21181027
TI  - [Tuberculosis among Brazilian indigenous individuals aged less than 15 years-old
      in State of Mato Grosso do Sul, Brazil].
AB  - INTRODUCTION: This study describes the epidemiological aspects of TB among
      Brazilian Native Indians aged less than 15 years-old in Mato Grosso do Sul,
      Brazil, between 2000 and 2006. METHODS: A retrospective observational study based
      on secondary data collected from the health system of Brazilian indigenous
      peoples, Special Indigenous Sanitary District (DSEI), and National System of
      Notifiable Diseases (SINAN) databases. The variables analyzed were: frequency of
      TB according to sex, age, clinical presentation and outcome. The Fisher test and
      the incidence tendency curve were calculated (p<0.01). RESULTS: TB prevalence was
      20.4% (224/1,096). The incidence rate decreased 14% per year during the study
      period. TB was more prevalent among Brazilian indigenous individuals aged less
      than 5 years-old and among those aged less than one year-old. More than half of
      TB cases were male and the most common clinical presentation was pulmonary TB
      (92.9%). Cure was the most common outcome (91.1%), followed by abandoned
      treatment (3.6%) and death (2.2%). CONCLUSIONS: The high cure rate, reduced
      mortality and the progressive decrease in TB incidence rate during the study
      period indicate the effectiveness of supervised treatment of the new TB control
      model implemented among Brazilian indigenous peoples on 2000.

PMID- 21181028
TI  - [Chagas' disease in the State of Maranhao, Brazil: record of acute cases from
      1994 to 2008].
AB  - INTRODUCTION: Chagas' disease is not considered an endemic disease in the State
      of Maranhao. However, entomological surveys showed high natural vector infection
      indices and acute cases have been identified in the last few decades. This study
      aimed to analyze the social, demographic and environmental conditions involved in
      transmission. METHODS: The study describes acute Chagas' disease identified from
      1994 to 2008. Information regarding the cases was obtained from the Information
      System for Notifiable Diseases (Sinan), National Health Foundation (Funasa)
      database and medical records. Entomological surveys were conducted from 2002.
      RESULTS: Data analysis identified 32 cases from 17 municipal districts, with
      84.4% of patients from rural areas. The disease was more frequent in men (67%).
      The most frequent occupation was student, 38.9% of cases, followed by farmer and
      hunter, 27.8%. CONCLUSIONS: The study suggests that transmission was vectorial
      and occurred in the wild or peridomicile.

PMID- 21181029
TI  - [Apical lesions in Chagas' heart disease patients: an autopsy study].
AB  - INTRODUCTION: The presence of an apical ventricular lesion increases the risk of
      intracardiac thrombosis and thromboembolic phenomena. The study evaluated the
      incidence of apical lesions and intracardiac thrombosis in Chagas' heart disease
      patients at autopsy. METHODS: A retrospective review of autopsies of Chagas'
      heart disease patients was conducted. Statistical analysis included comparison of
      clinical variables and autopsy findings between two groups: group A (apical
      lesions) and group B (no apical lesions). RESULTS: A total of 51 cases of Chagas'
      disease patients were studied: 25 in group A (mean age 53 years-old; 64% male)
      and 26 in group B. Apical lesions were verified in the left ventricle in 80% of
      cases. The prevalent clinical subtype in both groups was myopathic, but
      significant cardiac arrhythmia was present in 57.9% of patients in group A, while
      76.9% in group B did not present arrhythmias. Mean heart weight was 500.9 g in
      group A and 408.4 g in group B. The presence of thrombosis occurred in 60% of
      group A with 8 (53.3%) thrombi occurring in the apical lesion. CONCLUSIONS: The
      myopathic subtype was the most common clinical form in group A and the mean heart
      weight was statistically higher in this group. Clear prevalence of thrombosis was
      verified in group A, with 50% located in the apical lesion, whose main
      differential factor was a greater incidence of arrhythmias. Myopathy (heart
      weight above 500 g) was primordial for the presence of thrombosis in both groups.

PMID- 21181030
TI  - [Canine tegumentar leishmaniasis in the town of Balneario Camboriu in the State
      of Santa Catarina].
AB  - INTRODUCTION: The increase in American tegumentary leishmaniasis (ATL) cases in
      2005 was due to an outbreak that occurred in the towns of Itapema and Balneario
      Camboriu. This study aimed to determine the possible presence of infection by
      Leishmania sp in domestic dogs living in an endemic focus of ATL in the town of
      Balneario Camboriu and verify the existence of a correlation between the humoral
      and cellular immune responses, the presence of suggestive lesions and positivity
      in direct parasitological exams. METHODS: A total of 275 dogs were evaluated,
      examined according to clinic aspects, the development of delayed hypersensitivity
      to Immunoleish antigens and serological responses to the indirect
      immunofluorescence reaction and immunoenzymatic assay. RESULTS: Seven dogs
      presented suspect lesions, but Leishmania was not detected using the direct
      parasitological method. The serological result was 5.8% positivity using the IIFR
      technique, 6.2% by ELISA and 1.8% using the intradermal test. The total number of
      dogs positive for ATL using the serological exams and/or intradermal test was 24,
      indicating prevalence of 8.7% for ATL. CONCLUSIONS: Further studies are required
      to evaluate the participation of dogs in the epidemiological chain of ATL in
      Balneario Camboriu.

PMID- 21181031
TI  - [Clinical and radiological study of Surui indigenous children and adolescents,
      Amazon Region, Brazil].
AB  - INTRODUCTION: The average incidence coefficient of tuberculosis in Surui Indians
      from Rondonia was 2.500/100.000 inhabitants in 1991-2002. About 50% of these
      cases were reported in children < 15 years-old. METHODS: This study aimed to
      describe the clinical and radiological characteristics of children and
      adolescents identified as TB case contacts. A score system for the diagnosis of
      childhood TB was used and the procedures adopted by local health services were in
      accordance with national guidelines. RESULTS: 52 chest X-rays of 37 indigenous
      subjects were analyzed; of these, 51.9% were abnormal. Some X-rays showed more
      than two lesions, making a total of 36 independent events. Infiltrates (38.9%),
      calcifications (38.9%), cavitations (11.1%) and atelectasis/pleural effusion
      (11.1%) were observed. Among the abnormal images, 22.2% were probably indicated
      active TB and 33.3% showed sequelae. Confrontation with the guidelines revealed
      52.6% of divergent procedures. CONCLUSIONS: The presence of latent tuberculosis
      infection (LTBI) and active TB between children and adolescents are indicators of
      active and progressive transmission of Mycobacterium tuberculosis. The X-rays
      showed high frequencies of infiltrates and calcifications, which are compatible
      with primary infection in early childhood. However, these lesions are not
      different from those observed among other groups and do not suggest immune
      deficiencies. The divergences presented show that the best moment for the
      treatment of LTBI went unnoticed by local personnel. In conclusion, the use of a
      score system is fundamental for the correct diagnosis of TB in childhood, as is
      conducting bacilloscopy and sputum culture in adolescents able to expectorate.

PMID- 21181032
TI  - [Ecological aspects of Phlebotomines (Diptera: Psychodidae) in the urban area of
      Ponta Pora municipality, State of Mato Grosso do Sul, Brazil].
AB  - INTRODUCTION: The aim of this study was to carry out an analysis of urban
      phlebotomine fauna and a survey of infestations (intradomiciliary and
      peridomiciliary) in Ponta Pora municipality State of Mato Grosso do Sul. METHODS:
      Sand flies were collected with automatic CDC light traps, installed monthly on
      three consecutive nights, from 18 h to 6h, from September 2005 to September 2007.
      RESULTS: A total of 3,946 phlebotomines, representing eight species, were
      captured, among which was a large predominance of Lutzomyia longipalpis,
      presenting high indexes of frequency, constancy, abundance and dominance. Of the
      total, 82.9% were males and 17.1% females. The monthly average number (136.29 +/-
      152.01) of males captured being, much larger than that of females. Although the
      average number of phlebotomines in the intradomicile was much larger than that in
      the peridomicile, there was no significant statistical difference. A positive
      correlation was found between the abundance of phlebotomines and the average
      daily maximum temperature, precipitation and relative atmospheric humidity.
      CONCLUSIONS: The predominance of Lutzomyia longipalpis in Ponta Pora municipality
      is a reason for concern as regards the possibility of outbreaks of visceral
      leishmaniasis in the area, because this species is the main Leishmania chagasi
      vector not only in Mato Grosso do Sul but also nationwide.

PMID- 21181033
TI  - A semi-nested PCR assay for molecular detection of Paracoccidioides brasiliensis
      in tissue samples.
AB  - INTRODUCTION: Paracoccidioidomycosis is a systemic infection caused by
      Paracoccidioides brasiliensis. METHODS: In this study, a semi-nested PCR for
      paracoccidioidomycosis diagnosis was developed. The primers ITS1 and ITS4 were
      used in the first reaction, while the primers MJ03 and ITS1 primer were used in
      the second reaction. The semi-nested PCR was used to investigate biopsies of five
      patients with oral lesions that resembled paracoccidioidomycosis. RESULTS: The
      semi-nested PCR was positive for four samples and negative for a sample from a
      patient later diagnosed with leishmaniasis. CONCLUSIONS: The new semi-nested PCR
      describe is useful for paracoccidioidomycosis diagnosis.

PMID- 21181035
TI  - Phlebotomine sand flies (Diptera: Psychodidae: Phlebotominae) in the State of
      Pernambuco.
AB  - INTRODUCTION: Phlebotomine sand flies are small insects of great medical
      relevance. This article presents an updated list of the phlebotomine sand flies
      occurring in the State of Pernambuco, Brazil. METHODS: A review of literature
      published since the 1940s up to May 2010 was conducted and voucher material
      deposited in reference collections were studied. RESULTS: A total of 37
      phlebotomine species have previously been reported as occurring in Pernambuco,
      but the record of six species needs confirmation. CONCLUSIONS: This work provides
      an updated list of phlebotomine sand flies of Pernambuco, with some notes on
      their taxonomy, ecology, distribution and epidemiological relevance.

PMID- 21181034
TI  - Humoral immune response of patients bitten by the snake Bothrops erythromelas.
AB  - INTRODUCTION: Snake envenomings are a health problem in rural areas of tropical
      and subtropical countries, but little is known regarding the immune response
      presented by bitten individuals. The IgM production of patients bitten by
      Bothrops erythromelas snake was analyzed to identify the effectiveness of
      treatment in this type of envenomation. METHODS: Bothrops erythromelas venom was
      submitted to electrophoresis and transferred to a nitrocellulose sheet, following
      incubation with patients' sera. RESULTS: A 38 KDa protein was detected before and
      24 h after therapy. CONCLUSIONS: The result suggests that this protein could be
      used as a marker for individuals envenomed by Bothrops. erythromelas.

PMID- 21181036
TI  - [Leprosy reactions in discharged patients following cure by multidrug therapy].
AB  - INTRODUCTION: Reactional states are the main cause of nerve lesions and
      incapacities provoked by leprosy. METHODS: Retrospective study aimed at verifying
      the frequency of leprosy reactions in discharged patients following cure by
      multidrug therapy (MDT). RESULTS: Among patients who presented reactions during
      treatment, 35.5% continued after MDT; of those that did not present during
      treatment, only 12.7% presented after discharge; 63.4% multibacillary patients
      presented during and 31.7% after; 27.7% paucibacillary patients presented during
      and 8.3% after. CONCLUSIONS: A direct proportional relation exists between the
      presence of reactions during and after treatment. Multibacillary clinical forms
      present a greater frequency of reactions during and after cure.

PMID- 21181037
TI  - [Hepatite A outbreak in an urban area of Luziania, State of Goias, Brazil, 2009].
AB  - INTRODUCTION: This paper describes the investigation to confirm an outbreak of
      hepatitis A, presents the case distribution by person, time and place, formulates
      a hypothesis concerning the mode of transmission and presents the recommended
      measures for prevention and control. METHODS: A descriptive study of a case
      series and an environmental research were conducted. RESULTS: An outbreak of
      hepatitis A was confirmed beginning in March 2009. Forty one (71%) individuals in
      the town received untreated water in their households. Thermotolerant coliform
      bacteria were detected in 20/58 (34%) water samples. CONCLUSIONS: Consumption of
      contaminated water was the main hypothesis of virus transmission.

PMID- 21181038
TI  - Neurological involvement in visceral leishmaniasis: case report.
AB  - Visceral leishmaniasis is a severe and potentially fatal vector-borne disease.
      The most typical symptoms are fever, hepatosplenomegaly, weight loss, bleeding
      and bacterial infections. Neurological changes are rarely reported. This paper
      describes a child who presented with neurological signs as the first symptoms of
      leishmaniasis; tone was diminished and tremors in the extremities were observed.
      A diagnosis of visceral leishmaniasis was confirmed by parasite detection in the
      bone marrow. Symptoms were reversed by specific treatment. The nature of a
      possible mechanism of neurological involvement in visceral leishmaniasis remains
      unexplained.

PMID- 21181039
TI  - Cryptococcus gattii molecular type VGII as agent of meningitis in a healthy child
      in Rio de Janeiro, Brazil: report of an autochthonous case.
AB  - Cryptococcus gattii causes meningoencephalitis in immunocompetent hosts,
      occurring endemically in some tropical and subtropical regions. Recently, this
      fungus was involved in an outbreak in Vancouver Island and British Columbia
      (Canada). In this temperate region, the VGII type is predominant. The paper
      describes an autochthonous case of meningoencephalitis by C. gattii VGII in a
      previously health child in Rio de Janeiro, considered nonendemic region of
      Brazil. The fungus was identified by biochemical tests and the molecular type was
      determined by URA5-RFLP. The present report highlights the need for clinical
      vigilance for primary cryptococcal meningitis in nonendemic areas.

PMID- 21181040
TI  - Subdoses of primaquine in overweight patients and malaria vivax relapses: report
      of two cases in the Federal District, Brazil.
AB  - Two cases of malaria by Plasmodium vivax relapsed after treatment with drugs in
      doses recommended by the Ministry of Health are presented. Both patients were
      overweight and were followed in the Federal District, an area considered free
      from vector transmission of the disease. Radical cure was obtained after
      medication with the same drugs in weight proportional doses.

PMID- 21181041
TI  - [Stroke in a chronic autochthonous chagasic patient from the Brazilian Amazon].
AB  - An episode of stroke in a chronic autochthonous chagasic patient from the
      Brazilian Amazon is reported. This is the first documented case of a
      predominantly thromboembolic form of chronic Chagasic cardiopathy in the region.

PMID- 21181042
TI  - [Is it possible to control dengue?].

PMID- 21181043
TI  - [How to implement the airborne infection isolation room in health-care settings
      with occupational risk for Mycobacterium tuberculosis transmission?].

PMID- 21181044
TI  - Images in infectious diseases. Concomitant progressive multifocal
      leukoencephalopathy and disseminated paracoccidioidomycosis in an AIDS patient.

PMID- 21181048
TI  - Use of health information systems in small municipalities in Southern Brazil.
AB  - OBJECTIVE: To describe the use of health information systems in towns with fewer
      than 10,000 inhabitants. METHODS: Study conducted in the state of Rio de Grande
      do Sul, Southern Brazil, between 2003 and 2004. A self-administered questionnaire
      was sent to municipal managers, containing 11 single-choice questions, three
      multiple-choice questions and three open questions on the structure available,
      use of information, indicators valued and satisfaction with the systems. The
      questionnaire was answered by managers in 127 of the municipalities in this state
      with fewer than 10,000 inhabitants (37.7%). The responses were tabulated in an
      electronic spreadsheet and the differences between respondent and non-respondent
      municipalities were evaluated using the chi-square test, taking the significance
      level to be p < 0.05. RESULTS: All the municipalities had computers available
      (mean of three per municipality) and 94% had internet access. The personnel
      responsible for information system inputs and analysis were public employees
      (59%) who also performed other tasks. The systems most used related to budget
      control and transfer of funds. Data analysis and generation of information used
      in local planning was carried out in 59.1% of the municipalities. The indicators
      cited as important for local planning were the same ones used in arrangements
      agreed with the state, but there was difficulty in understanding the terms
      "indicators" and "statistical data". Only 4.7% were fully satisfied with the
      information obtained from the health information systems. CONCLUSIONS: Two
      realities coexisted: municipalities that perceived that inputs to health
      information systems were a task to be complied with because of orders from
      central levels, in contrast with municipalities that saw the potential for these
      systems but had difficulty in using them.

PMID- 21181047
TI  - Challenges of postgraduate human health programs in Brazil.
AB  - Recognition for the growing role of extra-academic demands and players in the
      dynamics of human resource training for the market and, in particular, for
      research is discussed. Their synergies with the movement towards maturation of
      the sectoral system of healthcare innovation and with the priorities of the
      Sistema Unico de Saude (Brazilian National Health System) are discussed. The
      methodological adequacy of the process for evaluating these trends used by the
      Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (Coordination Office
      for Advancement of University-level Personnel) is analyzed. In a general manner,
      these trends mean adding new indicators for technological and social productivity
      to the predominantly academic criteria that already exist. The continuation and
      deepening of ongoing initiatives aimed at bringing in new formats for
      postgraduate programs and courses and new courses customized for the demands of
      the extra-academic market, among other markets, either of a social or
      technological-business nature, are discussed. In addition, the deepening of
      initiatives for stimulating postdoctoral training work, which is scarce in
      Brazil, is discussed.

PMID- 21181049
TI  - Unnotified deaths and hospital admissions for tuberculosis in the municipality of
      Rio de Janeiro.
AB  - OBJECTIVE: To analyze underreporting of deaths and hospital admissions from
      tuberculosis to the Information System for Notifiable Diseases (SINAN). METHODS:
      Cases with tuberculosis as basic or associated cause of death were selected from
      the Brazilian Mortality Information System (SIM) and hospital admissions for
      tuberculosis as main or secondary cause from the Hospital Information System of
      the Brazilian Unified Health System (SIH-SUS), for residents in the municipality
      of Rio de Janeiro in 2004. Probabilistic record linkage was carried out between
      the SIM and SIH-SUS databases and the SINAN for the years 2002 to 2004. RESULTS:
      Out of the 542 deaths from tuberculosis in the period, 234 (43.2%) were not
      registered in the SINAN for the two previous years. As for the 1,079 admissions,
      238 (22.1%) failed to be notified. Seventy-one deaths were related to these
      admissions: 47 were registered out of the SIH-SUS by death, 24 occurred after
      discharge and seven remained unnotified in the SINAN. The elderly were 1.6 times
      (95%CI 1.074;2.516) less likely to be notified than younger patients, and those
      with at least a college education were 3.6 times (95%CI 1.384;11.022) less likely
      to be notified than those with no formal education. Patients under 15 were 4.8
      times (95%CI 2.757;8.452) less likely to be notified than those aged between 15
      and 59 years. Some regional health administration divisions showed a percentage
      of unnotified deaths of over 50% and this percentage ranged from 37.8% to 12.7%
      for hospital admissions. CONCLUSIONS: The data suggest problems in the detection
      of cases and point to obstacles in adequate and timely treatment, as well as to
      quality flaws in the information system, with differences among regions in the
      municipality.

PMID- 21181050
TI  - Evaluation of an obesity prevention program in adolescents of public schools.
AB  - OBJECTIVE: To evaluate the effects of an obesity prevention program on the
      dietary practices of public school adolescents. METHODS: An intervention was
      conducted with 331 students aged between 11 and 17 years, enrolled in the 5th and
      6th grades of two state public schools in the city of Niteroi, Southeastern
      Brazil, in 2005. These schools were categorized into "intervention schools" (IS)
      and "control schools" (CS) for comparison. Dietary practices were analyzed using
      self-administered questionnaires before and after the intervention period: fast
      food consumption; soft drink consumption; replacement of meals for snacks;
      consumption of fruits and vegetables; and type of food consumed during school
      breaks. Chi-square test and McNemar's test were applied to compare proportions,
      considering a value of p <0.05. RESULTS: In the baseline, 185 students
      participated in the IS (82.2% of those eligible) and 146 students participated in
      the CS (70.5% of those eligible). In the post-intervention phase, there was a
      loss of 10.3% of IS adolescents and 27.4% of CS ones. There were no significant
      changes in dietary practices in CS. In contrast, IS showed an increase in the
      proportion of students who reported not consuming snacks sold by street vendors
      (from 36.7% to 50.6%; p = 0.02) and adolescents who reported not replacing their
      lunch (from 44.5% to 65.2%; p<0.01) and dinner (from 38.4% to 54.3%; p<0.01) for
      snacks. The main favorable change was the reduction in the frequency of
      consumption of fast food snacks in IS, when compared to CS (from 72.7% to 54.4%;
      p = 0.001). CONCLUSIONS: Favorable changes in the adolescents' dietary practices
      were found and they encourage the implementation of programs of this nature.
      However, long-lasting interventions need to be implemented and evaluated in terms
      of their effectiveness.

PMID- 21181051
TI  - Contextual determinants of neonatal mortality using two analysis methods, Rio
      Grande do Sul, Brazil.
AB  - OBJECTIVE: To analyze neonatal mortality determinants using multilevel logistic
      regression and classic hierarchical models. METHODS: Cohort study including
      138,407 live births with birth certificates and 1,134 neonatal deaths recorded in
      2003, in the state of Rio Grande do Sul, Southern Brazil. The Information System
      on Live Births and mortality records were linked for gathering information on
      individual-level exposures. Sociodemographic data and information on the
      pregnancy, childbirth care and characteristics of the children at birth were
      collected. The associated factors were estimated and compared by traditional and
      multilevel logistic regression analysis. RESULTS: The neonatal mortality rate was
      8.19 deaths per 1,000 live births. Low birth weight, 1- and 5-minute Apgar score
      below eight, congenital malformation, pre-term birth and previous fetal loss were
      associated with neonatal death in the traditional model. Elective cesarean
      section had a protective effect. Previous fetal loss did not remain significant
      in the multilevel model, but the inclusion of a contextual variable (poverty
      rate) showed that 15% of neonatal mortality variation can be explained by varying
      poverty rates in the microregions. CONCLUSIONS: The use of multilevel models
      showed a small effect of contextual determinants on the neonatal mortality rate.
      There was found a positive association with the poverty rate in the general
      model, and the proportion of households with water supply among preterm newborns.

PMID- 21181052
TI  - Predictive validity of a questionnaire to identify older adults at risk for
      hospitalization.
AB  - OBJECTIVE: To test the predictive validity of the Probability of Repeated
      Hospital Admissions questionnaire among older adults. METHODS: A population-based
      cohort study with a 6-month follow-up was implemented with 515 non
      institutionalized older people (>60 years) cared for by the Family Health
      Strategy in the city of Progresso, Southern Brazil, in 2005. Participants
      answered eight objective questions that were entered in a logistic regression
      model to estimate the risk of future hospital admission, by risk strata. Survival
      analysis and the receiver operating characteristics curve were utilized to assess
      instrument validity. RESULTS: Among participants, 56.1% were women and 10.1% were
      hospitalized. The high-risk group had a 6.5 times greater frequency of
      hospitalization in comparison to the low-risk category. CONCLUSIONS: The
      instrument is effective in assessing the risk of hospitalization among older
      adults attended by the Family Health Program of the National Unified Health Care
      System.

PMID- 21181053
TI  - Combined use of job stress models and self-rated health in nursing.
AB  - OBJECTIVE: To identify combinations of two models of psychosocial stress at work
      among nursing teams and their associations with self-rated health. METHODS: This
      was a cross-sectional study among workers at three public hospitals in the
      municipality of Rio de Janeiro, Southeastern Brazil (N = 1307). In 2006, a
      multidimensional questionnaire including two scales for measuring stress at work
      (demand-control and effort-reward imbalance models) was administered. Partial and
      complete (including social support at work) demand-control models were
      considered, along with partial and complete (including excessive commitment to
      work) effort-reward models. Multiple logistic regression models were used to
      estimate adjusted odds ratios and their respective 95% confidence intervals.
      RESULTS: The dimensions of both models were independently associated with self
      rated health, with odds ratios between 1.70 and 3.37. The partial demand-control
      model was less associated with health (OR = 1.79; 95%CI 1.26;2.53) than was the
      partial effort-reward imbalance model (OR = 2.27; 95%CI 1.57;3.30). Incorporation
      of social support and excessive commitment to work increased the strength of the
      demand-control and effort-reward imbalance models, respectively. Increased
      strength of association was observed when the two partial models were combined.
      CONCLUSIONS: The results indicate that the effort-reward imbalance model
      performed better for this specific group and for the outcome evaluated, and that
      there was an advantage in using complete models or combinations of partial
      models.

PMID- 21181054
TI  - Brazilian validation of the Quality of Life Instrument/spirituality, religion and
      personal beliefs.
AB  - OBJECTIVE: To analyze the psychometric properties of the World Health
      Organization's Quality of Life Instrument--Spirituality, Religion and Personal
      Beliefs module (WHOQOL-SRPB). METHODS: The WHOQOL-SRPB, the Brief
      Spiritual/Religious Coping Scale (Brief-SRCOPE Scale), the WHOQOL-BREF and the
      Beck Depression Inventory (BDI) were consecutively applied in a convenience
      sample of 404 patients and workers of a university hospital and workers of a
      university, in the city of Porto Alegre, Southern Brazil, between 2006 and 2009.
      The sample was stratified by sex, age, health status and religion/belief. The
      retest of the two first instruments was conducted with 54 participants.
      Exploratory factorial analyses of the WHOQOL-SRPB with the method of main
      components were performed, without limiting the number of factors, and requiring
      eight factors concomitantly with the WHOQOL-BREF items. RESULTS: The Brazilian
      Portuguese version of the WHOQOL-SRPB (General SRPB-Domain) showed construct
      validity, with a discriminatory validity between believers and non-believers (t =
      7.40; p = 0.0001); concurrent criterion-related validity, distinguishing
      depressed individuals from non-depressed ones (t = 5.03; p = 0.0001); convergent
      validity with the WHOQOL-BREF (physical r = 0.18; psychological r = 0.46; social
      r = 0.35; environmental r = 0.29; global r = 0.23; p = 0.0001) and with the SRPB
      Domain of the WHOQOL-100 (r = 0.78; p = 0.0001); and convergent/discriminatory
      validity with the brief SRCOPE Scale (with positive SRCOPE r = 0.64; p =
      0.0001/negative SRCOPE r = -0.03; p = 0.554). Excellent test-retest reliability
      (t = 0.74; p = 0.463) and internal consistency (alpha = 0.96; intrafactorial
      correlation 0.87 > r > 0.60; p = 0.0001) were observed. The exploratory factorial
      analyses performed corroborated the eight-factor structure of the WHOQOL-SRPB
      multicenter study. CONCLUSIONS: The Brazilian Portuguese version of the WHOQOL
      SRPB showed good psychometric qualities and use valid and reliable in Brazil. It
      is suggested that new studies be conducted with specific populations, such as
      different religions, cultural groups and/or diseases.

PMID- 21181055
TI  - Surveillance of adverse effects following vaccination and safety of immunization
      programs.
AB  - The aim of the review was to analyze conceptual and operational aspects of
      systems for surveillance of adverse events following immunization. Articles
      available in electronic format were included, published between 1985 and 2009,
      selected from the PubMed/Medline databases using the key words "adverse events
      following vaccine surveillance", "post-marketing surveillance", "safety vaccine"
      and "Phase IV clinical trials". Articles focusing on specific adverse events were
      excluded. The major aspects underlying the Public Health importance of adverse
      events following vaccination, the instruments aimed at ensuring vaccine safety,
      and the purpose, attributes, types, data interpretation issues, limitations, and
      further challenges in adverse events following immunization were describe, as
      well as strategies to improve sensitivity. The review was concluded by discussing
      the challenges to be faced in coming years with respect to ensuring the safety
      and reliability of vaccination programs.

PMID- 21181056
TI  - Models of childbirth care and cesarean rates in different countries.
AB  - The paper reports the results of a literature review on cesarean rates and models
      of childbirth care in different countries according to their utilization of
      technology. There were reviewed 60 studies published between 1999 and 2010
      retrieved from the Brazilian Federal Agency for Support and Evaluation of
      Graduate Education (CAPES) and ProQuest databases. The Brazilian model of
      childbirth care relies on the physician-patient relationship, level of technology
      utilization and cesarean delivery.

PMID- 21181057
TI  - Hansen's disease control in the State of Sao Paulo: a historical analysis.
AB  - Leprosy is an infectious contagious disease known since Biblical times. Global
      effort for disease control reveals intricate convergences of national history and
      of medical, governmental, and international policies. The study describes the
      history of Hansen's disease and control actions undertaken in the state of Sao
      Paulo starting in the 19th century and its connection with the development of
      public health in that state, by means of a bibliographic and documental analysis.

PMID- 21181058
TI  - Regionalization and political dynamics of Brazilian health federalism.
AB  - The implications from the Brazilian federal structure on the regionalization of
      health actions and services in the National Unified Health System (SUS) were
      analyzed, considering that the regional health planning in Brazil takes place
      within the context of intergovernmental relations as an expression of cooperative
      federalism in health. The analysis was based on a historical approach to
      Brazilian health federalism, recognizing two development periods,
      decentralization and regionalization. Regional health planning of SUS was
      explored in light of the theoretical framework of federalism. It is concluded
      that relative centralization of the process is needed in intergovernmental
      committees to actualize federal coordination and that it is essential to consider
      formalizing opportunities for dissent, both in regional management boards and in
      the intergovernmental committees, so that the consensus decision-making can be
      accomplished in healthcare regionalization.

PMID- 21181059
TI  - Analysis of advertising material distributed through pharmacies and drugstores.
AB  - A documental analysis was conducted to evaluate advertising material distributed
      through pharmacies and drugstores according to their compliance with Resolutions
      n. 102/2000 and 96/2008 of the Collegiate Board of Brazil's National Agency for
      Sanitary Surveillance. Brochures distributed through five pharmacies and
      drugstores in the city of Tubarao, Southern Brazil, were collected between May
      and November 2008. The 17 analyzed brochures advertised 2,444 products, of which
      680 were medicines. Of these, 13.7% were controlled drugs, half of them had no
      registration number with the Ministry of Health and 77.9% had a registration
      number that did not match. Information on drug indications and safety were
      omitted. The results showed that the drug advertising materials were not in
      accordance with the aforementioned resolutions.

PMID- 21181060
TI  - [Prediction of risk of death with the use of the Charlson Comorbidity Index].

PMID- 21181062
TI  - Right to health and not to be harmed: a definition from evidence-based medicine.

PMID- 21181063
TI  - Medical teaching beyond graduation: undergraduate study groups.

PMID- 21181064
TI  - Serum cytokine levels in patients with chronic low back pain due to herniated
      disc: analytical cross-sectional study.
AB  - CONTEXT AND OBJECTIVE: the role of immune response and proinflammatory cytokines
      in the pathogenesis of chronic pain has been of growing interest. In order to
      evaluate whether there is any association between disc herniation and elevated
      cytokine levels, we measured cytokine levels in patients with chronic low back
      pain and in healthy subjects. DESIGN AND SETTING: analytical cross-sectional
      study at the Pain Clinic of Universidade Federal da Bahia (UFBA). METHODS:
      cytokine levels were measured using the enzyme-linked immunosorbent assay (ELISA)
      technique on 23 patients with low back pain (G1) and on 10 healthy subjects (G2).
      RESULTS: the levels of tumor necrosis factor-alpha [TNF-alpha] (G1 = 5.6 +/- 2.3
      pg/ml; G2 = 1.6 +/- 0.5 pg/ml; P = 0.01) and interleukin-6 [IL-6] (G1 = 4.1 +/-
      3.0 pg/ml; G2 = 0.9 +/- 0.4 pg/ml; P = 0.01) were higher in G1. There were no
      statistically significant differences in relation to interleukin-1 [IL-1] (G1 =
      0.5 +/- 0.3 pg/ml; G2 = 0.5 +/- 0.1 pg/ml; P = 1) or soluble tumor necrosis
      factor receptor [sTNF-R] (G1 = 572 pg/ml +/- 36; G2 = 581 +/- 50 pg/ml; P =
      0.87). CONCLUSION: The patients with chronic low back pain due to disc herniation
      presented higher levels of TNF-alpha and IL-6, but not of IL-1 or sTNF-R.

PMID- 21181065
TI  - Prevalence of common thrombophilia markers and risk factors in Indian patients
      with primary venous thrombosis.
AB  - CONTEXT AND OBJECTIVE: venous thrombosis occurs as a result of interaction of
      genetic and acquired factors including activated protein C resistance (APC-R),
      fibrinogen levels, antithrombin, protein C, protein S, lupus anticoagulants and
      anticardiolipin antibodies. This study was aimed at determining the prevalence of
      these common thrombophilia markers in Asian Indians with primary venous
      thrombosis. DESIGN AND SETTING: this was a cross-sectional study carried out in
      Mumbai. METHODS: samples from 78 patients with a confirmed diagnosis of venous
      thrombosis and 50 controls were tested. Semi-quantitative estimation (functional
      assays) of protein C, protein S and antithrombin was performed. Quantitative
      estimation of fibrinogen was done using the Clauss method. Lupus anticoagulants
      were screened using lupus-sensitive activated partial thromboplastin time and
      beta2-glycoprotein-I dependent anticardiolipin antibodies were estimated by
      ELISA. APC-R was measured using a clotting-based method with factor V deficient
      plasma and Crotalus viridis venom. Statistical analysis was performed using Epi
      info (version 6). RESULTS: the popliteal vein was the most commonly involved
      site. Forty-four samples (56%) gave abnormal results. The commonest were elevated
      fibrinogen and APC-R (17.9% each), followed by low protein S (16.6%).
      CONCLUSIONS: this study confirms the literature findings that fibrinogen level
      estimation and screening for APC-R are important for the work-up on venous
      thrombosis patients since these, singly or in combination, may lead to a primary
      thrombotic episode. The frequency of the other thrombophilia markers was higher
      among the patients than among the controls, but without statistically significant
      difference.

PMID- 21181066
TI  - Evolution of blood magnesium and phosphorus ion levels following thyroidectomy
      and correlation with total calcium values.
AB  - CONTEXT AND OBJECTIVE: magnesium ion concentration is directly related and
      phosphorus ion concentration is inversely related to calcemia. The aim of this
      study was to evaluate the evolution of magnesium and phosphorus ion levels in
      patients undergoing thyroidectomy and correlate these with changes to calcium
      concentration. DESIGN AND SETTING: prospective study at the Alpha Institute of
      Gastroenterology, Hospital das Clinicas, Universidade Federal de Minas Gerais.
      METHODS: the study included 333 patients, of both genders and mean age 45 +/- 15
      years, who underwent thyroidectomy between 2000 and 2005. Total calcium,
      phosphorus and magnesium were measured in the blood preoperatively and 24 and 48
      hours postoperatively. Ionic changes were evaluated according to the presence or
      absence of postoperative hypocalcemia. RESULTS: there were statistically
      significant drops in blood phosphorus levels 24 and 48 hours after thyroidectomy,
      compared with preoperative values, in the patients without hypocalcemia. In the
      patients who developed hypocalcemia, there was a significant drop in plasma
      phosphorus on the first postoperative day and an increase (also statistically
      significant) on the second day, in relation to preoperative phosphorus levels. A
      significant drop in postoperative magnesium was also observed on the first and
      second days after thyroidectomy in the patients with hypocalcemia, in relation to
      preoperative levels. In the patients without hypocalcemia, the drop in magnesium
      was significant on the first day, but there was no difference on the second day.
      CONCLUSION: despite the postoperative changes, neither magnesium nor phosphorus
      ion levels had any role in post-thyroidectomy calcemia.

PMID- 21181067
TI  - Causes of discontinuity of blood donation among donors in Shiraz, Iran: cross
      sectional study.
AB  - CONTEXT AND OBJECTIVE: the adequacy of blood depends on blood donation rates and
      numbers of blood donors. To prepare adequate blood supplies, it is essential to
      investigate the barriers and factors that stop individuals from donating. This
      study aimed to identify the causes of lapsed donation at our center. DESIGN AND
      SETTING: cross-sectional study of volunteer blood donors in Shiraz, Iran.
      METHODS: we selected 850 donors who had donated between January 1, 2005 and June
      1, 2005, but had not donated again by June 2008. The participants were recruited
      by letter and telephone, and were interviewed using a specially designed
      questionnaire that contained items on demographic characteristics, donor
      motivations and reasons for not returning to donate. We used the chi-square test
      to identify associations between lapsed donor characteristics and reasons for
      declining to donate. RESULTS: the greatest motivation for donation was altruism.
      The most frequent reasons for lapsed donation were lack of time because of work
      and self-exclusion for medical reasons. Among first-time donors, the most
      frequent reasons were unsuitability for donation and lack of time. CONCLUSIONS:
      the reasons for not returning to donate are varied and may correlate with
      demographic characteristics. In this study, the main reason for not returning was
      lack of time. Changing donation hours so that donors can donate after work,
      providing mobile teams at workplaces, and shortening the duration of the donation
      process may help increase repeat donation rates.

PMID- 21181068
TI  - The effect of poverty on developmental screening scores among infants.
AB  - CONTEXT AND OBJECTIVE: child development is negatively influenced by multiple
      risk factors associated with poverty, thus indicating the importance of
      identifying the most vulnerable groups within populations that are apparently
      homogeneous regarding their state of socioeconomic deprivation. This study aimed
      to identify different levels of poverty in a population of low socioeconomic
      condition and to ascertain their influence on infants' neuropsychomotor
      development. DESIGN AND SETTING: cross-sectional study conducted at four Family
      Health Units in the Health District IV in the city of Recife, Brazil. METHODS:
      the sample comprised 136 infants aged 9 to 12 months, which represented 86% of
      all the infants in this age group, registered at the units studied. Socioeconomic
      status was assessed through a specific index and child development through the
      Bayley III screening test. RESULTS: around 20% of the families were in the lowest
      quartile of the socioeconomic level index and these presented the highest
      frequency of infants with suspected delay in receptive communication. Maternal
      and paternal unemployment negatively influenced receptive communication and
      cognition, respectively. Not possessing a cell phone (a reflection of low
      socioeconomic status) was associated with worse cognitive performance and gross
      motricity. Male infants showed a higher frequency of suspected delay in receptive
      communication. CONCLUSIONS: infants of more precarious socioeconomic status more
      frequently present suspected developmental delay. Development monitoring and
      intervention programs should be encouraged for this subgroup, thereby providing
      these children with a better chance of becoming productive citizens in the
      future.

PMID- 21181069
TI  - Narrative competence among hearing-impaired and normal-hearing children:
      analytical cross-sectional study.
AB  - CONTEXT AND OBJECTIVE: oral narrative is a means of language development
      assessment. However, standardized data for deaf patients are scarce. The aim here
      was to compare the use of narrative competence between hearing-impaired and
      normal-hearing children. DESIGN AND SETTING: analytical cross-sectional study at
      the Department of Speech-Language and Hearing Sciences, Universidade Federal de
      Sao Paulo. METHODS: twenty-one moderately to profoundly bilaterally hearing
      impaired children (cases) and 21 normal-hearing children without language
      abnormalities (controls), matched according to sex, age, schooling level and
      school type, were studied. A board showing pictures in a temporally logical
      sequence was presented to each child, to elicit a narrative, and the child's
      performance relating to narrative structure and cohesion was measured. The
      frequencies of variables, their associations (Mann-Whitney test) and their 95%
      confidence intervals was analyzed. RESULTS: the deaf subjects showed poorer
      performance regarding narrative structure, use of connectives, cohesion
      measurements and general punctuation (P < 0.05). There were no differences in the
      number of propositions elaborated or in referent specification between the two
      groups. The deaf children produced a higher proportion of orientation-related
      propositions (P = 0.001) and lower proportions of propositions relating to
      complicating actions (P = 0.015) and character reactions (P = 0.005). CONCLUSION:
      hearing-impaired children have abnormalities in different aspects of language,
      involving form, content and use, in relation to their normal-hearing peers.
      Narrative competence was also associated with the children's ages and the school
      type.

PMID- 21181071
TI  - The bicuspid aortic valve and related disorders.
AB  - Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation,
      affecting 1-2% of the population, with strong male predominance. Individuals may
      have a normally functioning BAV, and may be unaware of its presence and the
      potential risk of complications. However, they may easily develop aortic valve
      disorders: either stenotic or regurgitant, or both. Today, BAV is recognized as a
      syndrome incorporating aortic valve disorders and aortic wall abnormalities,
      including aortic dilation, dissection or rupture. Congenital or hereditary
      diseases such as ventricular septal defect, patent ductus arteriosus, coarctation
      of the aorta, Turner's syndrome, Marfan's syndrome etc., may frequently be
      associated with BAV. Infective endocarditis and occasionally thrombus formation
      may develop during the lives of BAV patients. Elevated cholesterol or C-reactive
      protein may be seen in laboratory findings of these patients. Beta-blockers and
      statins are the possibilities for medical treatment, and aortic valve
      repair/replacement and ascending aorta replacement are indicated for patients
      with a severely diseased aortic valve and aorta. Rigorous follow-up throughout
      life is mandatory after BAV has been diagnosed. The aim of the present article
      was to describe the implications of BAV and its associated disorders, and to
      discuss diagnostic and treatment strategies.

PMID- 21181070
TI  - Use of albumin as a risk factor for hospital mortality among burn patients in
      Brazil: non-concurrent cohort study.
AB  - CONTEXT AND OBJECTIVE: among burn patients, it is common to use colloidal
      substances under the justification that it is necessary to correct the oncotic
      pressure of the plasma, thereby reducing the edema in the burnt area and the
      hypotension. The aim here was to assess the risk of hospital mortality, comparing
      the use of albumin and crystalloid solutions for these patients. DESIGN AND
      SETTING: non-concurrent historical cohort study at Faculdade de Medicina de
      Marilia; within the Postgraduate program on Internal and Therapeutic Medicine,
      Universidade Federal de Sao Paulo; and at the Brazilian Cochrane Center. METHODS:
      burn patients hospitalized between 2000 and 2001, with registration in the
      Hospital Information System, who received albumin, were compared with those who
      received other types of volume replacement. The primary outcome was the hospital
      mortality rate. The data were collected from files within the Datasus software.
      RESULTS: 39,684 patients were included: 24,116 patients with moderate burns and
      15,566 patients with major burns. Among the men treated with albumin, the odds
      ratio for the risk of death was 20.58 (95% confidence interval, CI: 11.28-37.54)
      for moderate burns and 6.24 (CI 5.22-7.45) for major burns. Among the women, this
      risk was 40.97 for moderate burns (CI 21.71-77.30) and 7.35 for major burns (CI
      5.99-9.01). The strength of the association between the use of albumin and the
      risk of death was maintained for the other characteristics studied, with
      statistical significance. CONCLUSION: the use of albumin among patients with
      moderate and major burns was associated with considerably increased mortality.

PMID- 21181072
TI  - Extensive parapharyngeal and skull base neuroglial ectopia; a challenge for
      differential diagnosis and treatment: case report.
AB  - CONTEXT: neuroglial ectopia has been defined as a mass composed of differentiated
      neuroectodermal tissue isolated from the spinal canal or cranial cavity and
      remains rare. This lesion has to be considered in the differential diagnosis
      among newborn infants with classical symptoms of respiratory distress, neck mass
      and feeding difficulties. We present a rare case of extensive parapharyngeal and
      skull base neuroglial ectopia in 6-month-old girl who presented respiratory and
      feeding obstruction at birth. CASE REPORT: a six-month-old girl who presented
      upper respiratory and feeding obstruction at birth and was using tracheostomy and
      gastrostomy tubes was referred to our institution. Complete surgical excision of
      the mass consisted of a transcervical-transparotid approach with extension to the
      infratemporal fossa by means of a lateral transzygomatic incision, allowing
      preservation of all vital neurovascular structures. The anatomopathological
      examination showed a solid mass with nests of neural tissue, with some neurons
      embedded in poorly encapsulated fibrovascular stroma, without mitotic areas, and
      with presence of functioning choroid plexus in the immunohistochemistry assay.
      Neurovascular function was preserved, thus allowing postoperative decannulation
      and oral feeding. Despite the large size of the mass, the child has completed one
      year and six months of follow-up without complications or recurrence. Neuroglial
      ectopia needs to be considered in diagnosing airway obstruction among newborns.
      Surgical treatment is the best choice and should be performed on clinically
      stable patients. An algorithm to guide the differential diagnosis and improve the
      treatment was proposed.

PMID- 21181073
TI  - Association of anti-glomerular basement membrane antibody disease with
      dermatomyositis and psoriasis: case report.
AB  - CONTEXT: anti-glomerular basement membrane (anti-GBM) antibody syndrome is
      characterized by deposition of anti-GBM antibodies on affected tissues,
      associated with glomerulonephritis and/or pulmonary involvement. This syndrome
      has been described in association with other autoimmune disorders, but as far as
      we know, it has not been described in association with dermatomyositis and
      psoriasis. CASE REPORT: a 51-year-old man with a history of dermatomyositis and
      vulgar psoriasis presented with a condition of sensitive-motor polyneuropathy of
      the hands and feet, weight loss of 4 kg, malaise and fever. On admission, he had
      been making chronic use of cyclosporin and antihypertensive drugs for three
      months because of mild arterial hypertension. Laboratory tests showed anemia and
      leukocytosis, elevated serum urea and creatinine and urine presenting
      proteinuria, hematuria, leukocyturia and granular casts. The 24-hour proteinuria
      was 2.3 g. Renal biopsy showed crescentic necrotizing glomerulonephritis with
      linear immunoglobulin G (IgG) deposits on the glomerular basement membrane by
      means of direct immunofluorescence, which were suggestive of anti-GBM antibodies.
      The patient was then treated initially with methylprednisolone and with monthly
      cyclophosphamide in the form of pulse therapy.

PMID- 21181074
TI  - Biologics for rheumatoid arthritis: an overview of Cochrane reviews.
AB  - BACKGROUND: the biologic disease-modifying anti-rheumatic drugs (DMARDs) are very
      effective in treating rheumatoid arthritis (RA), however there is a lack of head
      to-head comparison studies. OBJECTIVES: to compare the efficacy and safety of
      abatacept, adalimumab, anakinra, etanercept, infliximab, and rituximab in
      patients with RA. METHODS: this 'Overview of Reviews' was done by including all
      Cochrane Reviews on Biologics for RA available in The Cochrane Library. We
      included only data on standard dosing regimens for these biologic DMARDs from
      placebo-controlled trials. The primary efficacy and safety outcomes were ACR50
      and withdrawals due to adverse events. We calculated Risk Ratios (RR) for
      efficacy, Odds Ratio (OR) for safety and combined estimates of events across the
      placebo groups as the expected Control Event Rate (CER). Indirect comparisons of
      biologics were performed for efficacy and safety using a hierarchical linear
      mixed model incorporating the most important study level characteristic (i.e.
      type of biologic) as a fixed factor and study as a random factor; reducing the
      between study heterogeneity by adjusting for the interaction between the
      proportion of patients responding on placebo and the duration of the trial. MAIN
      RESULTS: from the six available Cochrane reviews, we obtained data from seven
      studies on abatacept, eight on adalimumab, five on anakinra, four on etanercept,
      four on infliximab, and three on rituximab. The indirect comparison estimates
      showed similar efficacy for the primary efficacy outcome for all biologics with
      three exceptions. Anakinra was less efficacious than etanercept with a ratio of
      RRs (95% CI; P value) of 0.44 (0.23 to 0.85; P = 0.014); anakinra was less
      efficacious than rituximab, 0.45 (0.22 to 0.90; P = 0.023); and likewise
      adalimumab was more efficacious than anakinra, 2.34 (1.32 to 4.13; P = 0.003). In
      terms of safety, adalimumab was more likely to lead to withdrawals compared to
      etanercept, with a ratio of ORs of 1.89 (1.18 to 3.04; P = 0.009); anakinra more
      likely than etanercept, 2.05 (1.27 to 3.29; P = 0.003); and likewise etanercept
      less likely than infliximab, 0.37 (0.19 to 0.70; P = 0.002). AUTHORS'
      CONCLUSIONS: based upon indirect comparisons, anakinra seemed less efficacious
      than etanercept, adalimumab and rituximab and etanercept seemed to cause fewer
      withdrawals due to adverse events than adalimumab, anakinra and infliximab.
      Significant heterogeneity in characteristics of trial populations imply that
      these finding must be interpreted.

PMID- 21181075
TI  - Regular treatment with formoterol and an inhaled corticosteroid versus regular
      treatment with salmeterol and an inhaled corticosteroid for chronic asthma:
      serious adverse events.
AB  - BACKGROUND: an increase in serious adverse events with both regular formoterol
      and regular salmeterol in chronic asthma has been demonstrated in comparison with
      placebo in previous Cochrane reviews. This increase was significant in trials
      that did not randomise participants to an inhaled corticosteroid, but less
      certain in the smaller numbers of participants in trials that included an inhaled
      corticosteroid in the randomised treatment regimen. OBJECTIVES: we set out to
      compare the risks of mortality and non-fatal serious adverse events in trials
      which have randomised patients with chronic asthma to regular formoterol versus
      regular salmeterol, when each are used with an inhaled corticosteroid as part of
      the randomised treatment SEARCH STRATEGY: trials were identified using the
      Cochrane Airways Group Specialised Register of trials. Manufacturers' web sites
      of clinical trial registers were checked for unpublished trial data and Food and
      Drug Administration (FDA) submissions in relation to formoterol and salmeterol
      were also checked. The date of the most recent search was July 2009. SELECTION
      CRITERIA: controlled clinical trials with a parallel design, recruiting patients
      of any age and severity of asthma were included if they randomised patients to
      treatment with regular formoterol versus regular salmeterol (each with a
      randomised inhaled corticosteroid), and were of at least 12 weeks duration. DATA
      COLLECTION AND ANALYSIS: two authors independently selected trials for inclusion
      in the review and extracted outcome data. Unpublished data on mortality and
      serious adverse events were sought from the sponsors and authors. MAIN RESULTS:
      eight studies met the eligibility criteria of the review recruiting 6,163 adults
      and adolescents. There were seven studies (involving 5,935 adults and
      adolescents) comparing formoterol and budesonide to salmeterol and fluticasone.
      All but one study administered the products as a combined inhaler, and most used
      formoterol 50 mcg and budesonide 400 mcg twice daily versus salmeterol 50 mcg and
      fluticasone 250 mcg twice daily. There were two deaths overall (one on each
      combination) and neither were thought to be related to asthma. There was no
      significant difference between treatment groups for non-fatal serious adverse
      events, either all-cause (Peto OR 1.14; 95% CI 0.82 to 1.59, I2 = 26%) or asthma
      related (Peto OR 0.69; 95% CI 0.37 to 1.26, I2 = 33%). Over 23 weeks the rates
      for all-cause serious adverse events were 2.6% on formoterol and budesonide and
      2.3% on salmeterol and fluticasone, and for asthma-related serious adverse
      events, 0.6% and 0.8% respectively. There was one study (228 adults) comparing
      formoterol and beclomethasone to salmeterol and fluticasone, but there were no
      deaths or hospital admissions. No studies were found in children. AUTHORS'
      CONCLUSIONS: the seven identified studies in adults did not show any significant
      difference in safety between formoterol and budesonide in comparison with
      salmeterol and fluticasone. Asthma-related serious adverse events were rare, and
      there were no reported asthma-related deaths. There was a single small study
      comparing formoterol and beclomethasone to salmeterol and fluticasone in adults,
      but no serious adverse events occurred in this study. No studies were found in
      children. Overall there is insufficient evidence to decide whether regular
      formoterol and budesonide or beclomethasone have equivalent or different safety
      profiles from salmeterol and fluticasone.

PMID- 21181076
TI  - Pattern of care and results of radiotherapy in patients 80 years old and over.
AB  - BACKGROUND AND AIMS: Cancer incidence increases with age and several cancer types
      are observed in older patients, so the need for radiotherapy (RT) in treatment of
      older patients with cancer is also on the rise. This study's aims to evaluate
      retrospectively the pattern of care and the feasibility of RT in elderly patients
      (80 years old and over) treated with different intents, and the impact of RT
      prescription on survival. MATERIALS AND METHODS: We reviewed 191 patient charts
      from the years 2005-2007, recording age, intent of treatment, site, and type of
      RT. Crude and actuarial survival were estimated. RESULTS: One hundred patients
      were males (M) and 91 females (F); 162 were seen on an outpatient basis, 29 as
      inpatients. A total of 138 patients were recruited for RT; 113 were treated, 112
      completed RT. The ratio to all treated patients was 113/2125 (5.3%). Overall
      (treated and non-treated) cumulative survival probability was 71% for the first
      year, 45% for the second and 27% for the third. For treated patients, the
      cumulative survival probability was 67% for the first year, 43% for the second
      year and 23% for the third year, while for untreated patients it was 76% for the
      first year, 47% for the second year and 32% for the third year (Log-rank test: p
      = 0.23). CONCLUSIONS: RT did not decrease survival in elderly patients.

PMID- 21181077
TI  - [Obesity and outcomes in the ICU: an observational study].
AB  - OBJECTIVES: We examined the relationships among Body Mass Index (BMI) with or
      without Metabolic Syndrome (MetS), ICU length of stay (ICU-LOS), duration of
      mechanical ventilation and mortality among ICU patients. MATERIALS AND METHODS:
      This prospective observational study included all patients hospitalized in a 10
      bed polyvalent ICU over a period of one year and seven months. We divided the
      studied population into 4 groups by BMI values: group A: between 18.5 and 24.9
      (n=369); group B1: 25-39.9 without MetS (n=86); B2 group: 25-39.9 with MetS
      (n=72); group C: >40 (n=42). Major exclusion criteria were: age <18 years, death
      or cerebral death within 24 hours from ICU admission. The chi square test and the
      variance analysis were used to compare groups. Variables significantly associated
      with ICU mortality were entered in a multiple regression model, allowing the
      determination of independent predictors. RESULTS: 620 patients were included in
      the study. Their SOFA score was between 8 and 15. Significant differences between
      B1 and B2 subgroups were observed in ICU-LOS (p <0.01), duration of mechanical
      ventilation (p <0.01) and ICU mortality (p <0.01). We found no statistically
      significant differences in mortality between B2 and C groups, as well as between
      A and B1 groups (42.34%/45.15% vs 16.27%/19.07%, respectively). We found that a
      BMI >25 with MetS was an independent predictive factor of: lower ICU-LOS, lower
      duration of mechanical ventilation, higher mortality rate. CONCLUSIONS: In our
      study, a BMI >25 with MetS was significantly associated with increased morbidity
      and mortality in ICU patients.

PMID- 21181078
TI  - Burnout, hopelessness and suicide risk in medical doctors.
AB  - OBJECTIVES: The aim of the present study was to investigate the association
      between burnout and hopelessness in medical doctors. MATERIALS AND METHODS: We
      conducted an investigation of 133 medical doctors working either in a hospital
      setting or in general practice to explore the relationship between the level of
      burnout and hopelessness, a psychometric marker for suicide risk. The
      participants were administered the Oldenburg Burnout Inventory (OBI) and Beck's
      Hopelessness Scale (BHS). RESULTS: Burnout is an important issue in mediating the
      level of hopelessness. Doctors with high hopelessness had higher scores on the
      disengagement factor (2.61+/-0.47 vs 2.14+/-0.41; t131=-4.37; p<0.001; Cohen
      D=1.07), and on the exhaustion factor (2.68+/-0.65 vs 2.19+/-0.54; t131=-3.39;
      p<0.001; Cohen D=0.82) than doctors with low hopelessness. A multivariate
      regression analysis confirmed that disengagement and exhaustion are significant
      predictors of the BHS scores. CONCLUSIONS: People in charge of workers' health
      should pay particular attention to the level of burnout in doctors, intervene
      with changes in the work environment and evaluate the impact of such procedures.

PMID- 21181079
TI  - Comparison of Chlorella vulgaris dressing and sodium alginate dressing: an
      experimental study in rats.
AB  - BACKGROUND AND AIMS: Chlorella vulgaris (CV) is a green microalgae enriched with
      nutrients, vitamins, minerals and chlorophyll. The aim of our study was to
      evaluate the potential wound healing effects of CV as a dressing while comparing
      it to sodium alginate dressing. MATERIALS AND METHODS: Fifteen Sprague-Dawley
      rats were divided into three groups consisting of control (normal-wound with no
      dressing), CV and sodium alginate dressings. Wound was created on the dorsal
      surface of rats using a 6-mm sterilized punch biopsy. The wounds were examined on
      days 3, 6, 9 and 12 for dryness, exudation, contraction, period of
      epithelialization, complete wound closure and scar formation. All rats were
      sacrificed on day 12 and the granulation tissue formed on the wound was excised
      for the histological examination using Hematoxylin and Eosin stain (H&E).
      RESULTS: The wound's size treated with CV dressing was significantly reduced
      (p<0.05) compared to the control and sodium alginate treated wounds. H&E staining
      showed that CV dressing minimized the formation of scar tissue during the healing
      process. Although there was no statistically significant difference in the
      complete wound closure and period of epithelialization among the groups, a
      significant difference was observed regarding the dryness, exudation and scar
      formation in the wound. CONCLUSION: CV extract can be used as an effective
      supplement for wound dressing.

PMID- 21181080
TI  - Setting up an emergency stock for metabolic diseases.
AB  - INTRODUCTION: Therapeutic management of inborn errors of metabolism (IEMs) is
      complicated. The drugs involved are classified as orphan, and their supply
      depends on whether they are orphan medicines, investigational drugs, or need to
      be prepared as a compounded formula. MATERIALS AND METHODS: We analyzed emergency
      criteria, availability, and permanent location of metabolic drugs within the
      hospital. Information on therapeutic usage, administration, and dosage was also
      recorded. RESULTS: A stock for treating IEMs should include chelating agents,
      drugs to treat deficiencies, enzyme supplements, and other specific treatments.
      Hyperammonemia was considered to be life-threatening; therefore, an emergency
      supply of drugs to treat this condition should be kept permanently in the
      hospitalization unit. CONCLUSIONS: Emergency drug stocks are highly recommended
      in tertiary hospitals in order to improve care for patients susceptible to IEM.

PMID- 21181081
TI  - Massive heterotopic ossification in Guillain-Barre syndrome: a rare case report.
AB  - Heterotopic ossification (HO) is the abnormal development of bone within soft
      tissue and a rare complication in Guillain-Barre syndrome (GBS). Only a few cases
      had been reported so far. We present the case of a 39-year-old man who had been
      diagnosed to have GBS about 10 years ago, presenting with severe limitation of
      both active and passive range of motion in bilateral shoulder, elbow and hip
      joints and was found to have massive heterotopic ossification. In our patient, it
      could be a myriad of factors such as prolonged ICU stay with mechanical
      ventilation and hypoxia, long-standing immobilization and hypomobility with
      incomplete flaccid paralysis.

PMID- 21181082
TI  - Internal hernia through the mesosalpinx: a lesson to learn.
AB  - An internal hernia through the mesosalpinx is a rare condition which is often
      overlooked. We report the case of a 65-year-old lady who presented with features
      of small bowel obstruction. At laparotomy, a gangrenous ileum was found to have
      herniated through a defect in the right mesosalpinx. We discuss this rare cause
      of a small bowel obstruction and its diagnostic dilemma.

PMID- 21181083
TI  - Clinico-anatomical description of an accessory flexor pollicis longus.
AB  - Several instances of accessory musculature of the upper extremity are now
      recognized. During regular dissection class of undergraduate medical students, we
      observed an important anatomic variation pertaining to the flexor pollicis longus
      muscle (FPL) in the left upper limb of an adult male cadaver. An accessory muscle
      belly extending from the deep aspect of flexor digitorum superficialis (FDS) to
      the tendon of the FPL was observed in the flexor surface of the antebrachium. The
      description of Gantzer's muscle (GM) is well elucidated in anatomical archives
      and is described as an accessory muscle extending from the superficial to the
      deep flexors of the digits.

PMID- 21181084
TI  - The role of physical activity in the prevention and treatment of chronic
      diseases.
AB  - The aim of this review is to assess the current evidence in scientific literature
      that supports the use of physical activity as a fundamental tool for primary and
      secondary prevention and to encourage its use conscientiously. Observational
      studies and international guidelines have been examined to evaluate the positive
      effects of physical activity as primary prevention on some of the most common
      diseases. We have also evaluated those studies which demonstrate that the
      association of physical activity with drug therapy in chronic diseases results in
      a better prognosis. We researched the Cochrane Controlled Trials Register,
      MEDLINE, PubMed up to January 2009. Furthermore, we screened references in
      relevant reviews and clinical trials. Sixty four studies were included in the
      review and cited as giving consistent evidence for the utilization of physical
      activity to improve health. There is strong evidence that, according to
      international guidelines, physical activity should be adopted as a tool in the
      prevention and treatment of many chronic diseases.

PMID- 21181085
TI  - Sublingual immunotherapy for treating respiratory allergy: a review on its
      effectiveness and suitability.
AB  - Sublingual immunotherapy (SLIT) was introduced in the treatment of respiratory
      allergy as an option to subcutaneous immunotherapy (SCIT), which is clinically
      effective but has the problem of adverse systemic reactions, quite rare but
      sometimes life-threatening. A large number of trials, globally evaluated in
      several meta-analyses, demonstrated that SLIT is an efficacious treatment for
      allergic rhinitis and allergic asthma and has a satisfactory safety profile,
      severe reactions being extremely rare, though an increased risk is apparent in
      subjects undergoing SLIT because of previous systemic reactions to SCIT. The
      suitability of SLIT is ensured by a good compliance, higher than reported for
      SCIT, the injections being a major factor for noncompliance with the latter, and
      by its cost-effectiveness performances. In fact, a number of studies showed that
      SLIT may be very beneficial to the healthcare system, especially after its
      stopping, when there is no more the cost of the treatment but its efficacy on
      symptoms persists.

PMID- 21181086
TI  - [Near Infrared Spectroscopy for cerebral monitoring during cardiovascular
      surgery].
AB  - Near-infrared spectroscopy (NIRS) is an optical imaging technique for medical
      applications, able to monitor the variation of hemoglobin saturation into the
      tissues. The NIR photon passes through the biological tissue following a path
      similar to a more or less complex split. The NIR absorption of photons is
      proportional to the concentration of chromophores (pigments that absorb the light
      in the spectral region of interest). NIRS probes are used as the light source on
      the same side of the source receiver, being this last able to capture the photons
      after their journey into the tissues. The NIRS methodology may be applied as an
      imaging technique for various organs. In this review the authors describe the use
      of NIRS for the continuous monitoring of regional cerebral oxygen saturation in
      the course of cardiovascular surgical procedures. Thanks to the NIRS technique,
      changes in cerebral oximetry can be monitored continuously during cardiovascular
      surgery. A desaturation greater than 20% of baseline or an rSO2 absolute value
      less than 50%, are associated with a reduction of the cortical somatosensory
      evoked potentials and an increase of neurological damage and / or cognitive
      impairment. During carotid surgery, reduction and / or asymmetries of rSO2 value
      are encountered in the course of intraoperative clamping causing cerebral
      hypoperfusion. Instead, rSO2 increase may predict hyperperfusion syndrome after
      carotid stenting or endarterectomy. Cerebral hyperperfusion syndrome is rare, but
      often fatal once it has established. The NIRS may represent an added value in
      those patients. The NIRS is also applied during surgery performed with
      cardiopulmonary bypass, including aortic arch surgery with cardiocirculatory
      arrest. Continuous monitoring of any changes in cerebral rSO2 allows a rapid
      treatment in the aim to improve the psycho-neurological outcome of patients
      undergoing this type of surgery.

PMID- 21181088
TI  - TACT glossary: technology.
AB  - The term technology is derived from the Greek words tekhne and logos. Technique
      and technic(s) also come from tekhne. This Greek word and its Latin equivalent
      ars both belong to the same semantic field, referring primarily to a skill or
      practical process, a know-how and its products, be they objects or actions.
      Technology can, therefore, mean two things: i) either a scientific knowledge of
      tekhne or ii) a tekhne accompanied by science, that is, a know-how accompanied by
      a know-why. We shall normally understand technology to have this second meaning,
      as tekhne accompanied by or derived from science.

PMID- 21181087
TI  - White matter hyperintensities, suicide risk and late-onset affective disorders:
      an overview of the current literature.
AB  - White matter hyperintensities (WMHs) refer to areas of hyperintense signal on T2-
      or proton density-weighted brain magnetic resonance imaging. Although WMHs are a
      common finding in patients with bipolar disorder (BD), particularly with a later
      disease onset, some studies report a higher frequency of WMHs only in unipolar
      affective disorders. We reviewed the literature examining examining both the
      severity and presence of WMHs in late life and particularly in individuals with
      late-onset BD (LOBD). Studies investigating white matter lesions in LOBD were
      systematically retrieved and the reference lists of these studies were scanned
      for additional relevant studies of neuroimaging in LOBD. The majority of
      neuroimaging studies reported an association between older age and LOBD and the
      presence of WMHs in LOBD. Also, we found in a small sample of patients
      preliminary evidence of a significant relationship between older age with late
      onset BD and WMHs having a higher prevalence of cardiovascular and
      cerebrovascular risk factors. In conclusion over 60 years older individuals with
      LOBD and WMHs might have a type of illness characterized by more
      neuropathological changes and biologically different compared to non LOBD. This
      is consistent with the hypothesis of vascular mania. WMHs could be a reliable
      biological risk marker for late onset mood disorders.

PMID- 21181089
TI  - TACT glossary: technoscience.
AB  - The term technoscience (T) indicates the complex interactions between
      contemporary science and technology, that have become practically inseparable.
      From an epistemological point of view, T only considers the quantitative
      knowledge in a reductionist way. Nature has been reduced to a machine that works
      according to laws learnt through the experimental science. At present, technical
      efficiency represents an operational dominion on Nature; it gives the power to
      those who possess it. Scientists, considered as visionaries, have the assignment
      to lead society. They create new cosmos-visions that are technocentric, thus Ts
      use the human being as subject of experimentation and they transform some
      essential dimensions of the human being. All this suggests the necessity of an
      ethical evaluation of the action integration of different subjects in what we
      call integrated action. This configuration involves ethical obligations for the
      agent: he/she has to act preserving and allowing the collaboration, and
      respecting the professional's individual responsibility.

PMID- 21181090
TI  - TACT glossary: toys.
AB  - Toys denote objects used in playing. From the first examples of toys made of
      materials available in the environment and manufactured by parents or by children
      themselves only for recreational purpose, toys have evolved into more
      sophisticated devices which integrate mechanics, electronics and informatics
      (mechatronic toys) used in several different application fields. There are two
      main kinds of mechatronic toys: sensorized toys are passive toys equipped with a
      set of sensors used to record user/toy interactions; robotic toys are artefacts
      or computers, usually self-propelled with the help of motors, which collect
      information from the surrounding environment by sensors, and decode this
      information into behaviors consistent with them. This entry explores the use of
      the word "toys" from a technological point of view focussing on mechatronic toys
      and their applications.

PMID- 21181091
TI  - Regulation of p38 MAPK phosphorylation inhibits chondrocyte apoptosis in response
      to heat stress or mechanical stress.
AB  - Activation of p38 MAPK has been associated with a stress response and with
      apoptotic processes. However, the function of p38 MAPK in chondrocytes is not
      clearly understood. In this study, we analyzed the expression of p38 MAPK in
      chondrocytes and investigated the function of p38 MAPK in response to heat stress
      and mechanical stress. Chondrocytes were isolated from human cartilage and
      cultured. Expression of p38 and phosphorylated p38 in cartilage of patients with
      osteoarthritis (OA) was compared to those in normal cartilage by
      immunohistochemistry and Western blotting. Human knee chondrocytes were exposed
      to heat stress or mechanical stress. Normal knee chondrocytes were pre-treated
      with SB203580 or p38 small interfering RNA (siRNA) before induction of heat
      stress or mechanical stress. Chondrocyte apoptosis was detected by TUNEL staining
      and Western blotting of cleaved caspases. OA and normal chondrocytes expressed
      p38; however, OA chondrocytes showed much higher phosphorylated p38 compared to
      normal chondrocytes. Heat stress or mechanical stress induced apoptosis and
      increased phosphorylated p38 in normal chondrocytes. The TUNEL positive cells and
      expression levels of phosphorylated p38 in response to stress decreased when
      chondrocytes were incubated with SB203580 or transfected with siRNA against p38.
      In conclusion, we have demonstrated that heat stress or mechanical stress
      increased chondrocyte apoptosis via phosphorylation of p38. Stress-induced
      chondrocyte apoptosis decreased due to inhibition of p38 MAPK activation. In
      contrast, the phosphorylation of p38 MAPK increased in OA chondrocytes. Our
      results show that down-regulation of p38 MAPK activation inhibits chondrocyte
      death induced by heat stress or mechanical stress.

PMID- 21181092
TI  - Glutathione S-transferase P1 (GSTP1) suppresses cell apoptosis and its regulation
      by miR-133alpha in head and neck squamous cell carcinoma (HNSCC).
AB  - The glutathione S-transferase P1 (GSTP1) protein plays several critical roles in
      both normal and neoplastic cells, including phase II xenobiotic metabolism,
      stress responses, signaling and apoptosis. Overexpression of GSTP1 has been
      observed in many types of cancer, including head and neck squamous cell carcinoma
      (HNSCC). However, the role of GSTP1 in HNSCC is not well understood. We
      investigated the role of GSTP1 in two HNSCC cell lines, HSC3 and SAS. Silencing
      of GSTP1 revealed that cancer cell proliferation was significantly decreased in
      both cell lines. In addition, the frequency of apoptotic cells increased
      following si-GSTP1 transfection of HSC3 and SAS cell lines. Growing evidence
      suggests that microRNAs (miRNAs) negatively regulate gene expression and can
      function as oncogenes or tumor suppressors in human cancer. Based on the results
      of web-based searches, miR-133alpha is a candidate miRNA targeting GSTP1. Down
      regulation of miR-133alpha has been reported in many types of human cancer,
      including HNSCC. Transient transfection of miR-133alpha repressed the expression
      of GSTP1 at both the mRNA and protein levels. The signal from a luciferase
      reporter was significantly decreased at one miR-133alpha target site at the 3'UTR
      of GSTP1, suggesting that miR-133alpha directly regulates GSTP1. Our data
      indicate that GSTP1 may have an oncogenic function and may be regulated by miR
      133alpha, a tumor suppressive miRNA in HNSCC. The identification of a novel
      oncogenic pathway could provide new insights into potential mechanisms of HNSCC
      carcinogenesis.

PMID- 21181093
TI  - Exosomes in the ascites of ovarian cancer patients: origin and effects on anti
      tumor immunity.
AB  - This study was performed to identify the origin of the ascites-derived exosomes
      from patients with ovarian cancer and to observe the effect of exosomes on anti
      tumor immunity. Exosomes were isolated from the ascites of patients with ovarian
      epithelial cancer by ultracentrifugation plus density gradient centrifugation.
      The origin of exosomes was identified by immunoelectronmicroscopy (IEM). The
      growth curve of the tumor cell line SKOV3 cultured with or without exosomes was
      analyzed. The apoptosis of autogeneic tumor cells (ATCs) and SKOV3 cells affected
      by exosomes was measured by flow cytometry (FCM) and light phase contrast
      microscopy. The cytotoxic effect of the peripheral blood mononuclear cells
      (PBMCs) stimulated by exosomes and/or dendritic cells (DCs) on ovarian cancer
      cells was measured using a CCK-8 assay. The levels of IFN-gamma released by PBMCs
      stimulated by exosomes and/or DCs were measured by ELISA. The apoptosis of PBMCs
      and DCs affected by exosomes was measured by FCM and light microscopy. Whether
      the mature process of DCs was affected by exosomes was studied by FCM. The ratio
      of CD4+ T cell and CD8+ T cell were measured by FCM. FasL and TRAIL molecules on
      exosomes were detected by western blot analysis. The human FasL antagonistic
      antibody was used to block the apoptosis of DCs and PBMCs induced by exosomes.
      The receptors of TRAIL DR4 and DR5 on PBMCs and DCs were detected by FCM. In 41
      patients examined, we isolated exosomes from the ascites of 35 patients. We
      detected TCR, CD20, HLA-DR, B7-2, HER2/neu, CA125 and Histone H2A on exosomes. We
      found that exosomes might impair the cytotoxic activity of PBMCs when DCs are
      present. We found that exosomes had no effect on the growth and apoptosis of
      SKOV3 cells. However, exosomes may induce apoptosis of precursors, mature DCs and
      PBMCs. We found that FasL and TRAIL were present in the exosome suspension and
      addition of an anti-FasL antibody may decrease the percentage of apoptosis of DCs
      and PBMCs. We conclude that exosomes exist in ascites of 85.4% of patients with
      ovarian cancer. Moreover, these exosomes may be of multi-origin. Exosomes had no
      effect on the growth and apoptosis of tumor cells but impaired the cytotoxic
      activity of PBMCs in the presence of DCs. Exosomes also may induce apoptosis of
      the precursors of DCs, DCs and PBMCs. FasL and TRAIL on exosomes may partly
      account for the apoptosis of cells of the immune system.

PMID- 21181094
TI  - Downregulation of uPA/uPAR inhibits intermittent hypoxia-induced epithelial
      mesenchymal transition (EMT) in DAOY and D283 medulloblastoma cells.
AB  - Hypoxia is known to induce overexpression of the urokinase plasminogen activator
      (uPA) and its receptor (uPAR) and thus overexpression promotes uPAR-mediated
      survival signaling in various cancers. Moreover, hypoxia/ overexpression of uPAR
      in cancer cells promote the epithelial-mesenchymal transition (EMT) and thereby
      invasiveness and metastasis. In this study, we show that intermittent hypoxia has
      a more pronounced effect than chronic hypoxia and contributes to EMT, invasion
      and migration in medulloblastoma cells. Intermittent hypoxia induced expression
      of mesenchymal markers (i.e., SNAIL, Vimentin and N-cadherin) and reduced
      expression of epithelial markers (i.e., Zo-1, E-cadherin) in medulloblastoma
      cells. Further, intermittent hypoxia also leads to enhancement in cell invasion,
      migration and angiogenesis in medulloblastoma cells. Intermittent hypoxia also
      inhibited expression of pro-anti-apoptotic proteins (Bax and Bad), and induced
      expression of anti-pro-apoptotic proteins (Bcl2 and Bcl-xL), and activation of
      ERK in medulloblastoma cells. Transcriptional inactivation of either uPA or uPAR
      inhibits the intermittent hypoxia-induced invasion and migration, and expression
      of Vimentin. uPA/ uPAR downregulation also induces E-cadherin expression and
      inhibits activation of ERK. Thus, transcriptional inactivation of either uPA or
      uPAR enhances the apoptotic response in medulloblastoma cells exposed to
      intermittent hypoxia. This study provides evidence of the anti-tumor efficacy of
      down-regulation of uPA or uPAR in medulloblastoma tumors to target hypoxia
      induced cell EMT, invasion and migration, to achieve better therapeutic outcomes
      in the treatment of malignant medulloblastoma.

PMID- 21181095
TI  - Na+/K+-ATPase alpha3 mediates sensitivity of hepatocellular carcinoma cells to
      bufalin.
AB  - Bufalin, a major bioactive component of the Chinese medicine Chansu, has been
      reported to exhibit significant antitumor activity against various cancer cell
      lines. However, the exact mechanism remains unclear. In this study, we
      demonstrated that bufalin inhibited the growth of hepatocellular carcinoma (HCC)
      cells in a dose-dependent manner, which correlated with the expression level of
      Na+/K+-ATPase alpha3 in HCC cells. The IC50 of bufalin markedly increased when
      Na+/K+-ATPase alpha3 was silenced by RNA interference. Furthermore, we show that
      bufalin increased the phosphorylation of Akt and ERK1/2 while inhibited FoxO3a
      expression. Thus, our study suggests that Na+/K+-ATPase alpha3 might serve as a
      therapeutic target for bufalin in HCC, and its expression status may help predict
      sensitivity of HCC cells to bufalin treatment.

PMID- 21181096
TI  - [Home monitoring of an incessant VT in an ICD patient].
AB  - Due to the increasing number of patients and complexity of modern tachycardia
      devices, efficient therapy monitoring as offered by telemedicine monitoring is of
      increasing importance. The potential advantages of remote control for patient
      management include early detection of device-related technical problems and
      arrhythmias. We report the case of an ICD patient with incessant ventricular
      tachycardia in whom immediate arrhythmia transmission was monitored by remote
      control.

PMID- 21181097
TI  - [Coronary artery disease in HIV-infected subjects. Results of 101 coronary
      angiographies].
AB  - BACKGROUND: The introduction of antiretroviral therapy has brought cardiac
      disease as a comorbidity in HIV-infected patients in particular into focus. The
      present study analyses the results of coronary angiography in this patient
      population. METHODS: Over a time period of 12 years, 101 coronary angiographies
      were performed in HIV-infected patients. A retrospective analysis included
      demographic parameters, cardiac history, cardiovascular risk factors, HIV
      specific parameters including antiretroviral therapy and the results of coronary
      angiographies. RESULTS: Of the subjects included in the study, 89% were men. The
      mean age in the analysed population was 50.2 years at the time of coronary
      angiography. Patients had an elevated rate of cardiovascular risk factors
      including diabetes mellitus (15.9%), arterial hypertension (65.9%),
      hyperlipidemia (56.8 %) and smoking (68.2 %). Primary coronary angiography
      demonstrated coronary disease in 59.1%. Of all patients with coronary artery
      disease, 70% underwent coronary intervention. Subjects who underwent coronary
      intervention exhibited hyperlipidemia significantly more often (77.8% vs. 42.3%,
      p=0.02). Cardiovascular risk factors play a prominent role in the development of
      premature arteriosclerosis in HIV-infected patients. Furthermore, our data
      highlight the importance of invasive diagnostics in this patient group.

PMID- 21181098
TI  - [Infusion therapy for neonates, infants and children].
AB  - Intravenous administration of fluids, electrolytes and glucose are the most
      common interventions in hospitalized pediatric patients. Parenteral fluid
      administration can be life-saving, however, if used incorrectly it also carries
      substantial risks. Perioperatively, adequate hydration, prevention of electrolyte
      imbalances and maintenance of normoglycemia are the main goals of parenteral
      fluid therapy. Conceptionally, the distinction between maintenance requirements,
      deficits and ongoing loss is helpful. Although the pathophysiological basis for
      parenteral fluid therapy was clarified in the first half of the 20th century,
      some aspects still remain controversial. In newborn infants, rational parenteral
      fluid therapy must take into account large insensible fluid losses, adaptive
      changes of renal function in the first days of life and the fact that neonates do
      not tolerate prolonged periods of fasting. In older infants the occurrence of
      iatrogenic hyponatremia with the use of hypotonic solutions has led to a critical
      reappraisal of the validity of the Holliday-Segar method for calculating
      maintenance fluid requirements in the postoperative period. Pragmatically, only
      isotonic solutions should be used in clinical situations which are known to be
      associated with increases in antidiuretic hormone (ADH) secretion. In this
      context, it is important to realize that in contrast to lactated Ringer's
      solution, the use of normal saline can lead to hyperchloremic acidosis in a dose
      dependent fashion. Although there is no convincing evidence that colloids are
      better than crystalloids, there are clinical situations where the use of the more
      expensive colloids seems justified. It may be reasonable to choose a solution for
      fluid replacement which has a composition comparable to the composition of the
      fluid which must be replaced. Although hypertonic saline can reduce an elevated
      intracranial pressure, this therapy cannot be recommended as a routine procedure
      because there is currently no evidence that this intervention improves long-term
      outcome in pediatric patients with traumatic brain injury.

PMID- 21181099
TI  - [Diffuse brown discoloration of skin, mucosa and urine].
AB  - A 45-year-old woman presented with diffuse melanosis, icteric sclera and
      melanuria. Physical examination revealed a massive nodular melanoma with
      ulceration and satellite metastases on the back. Further investigation showed
      distant cutaneous and visceral metastasis. After palliative debulking along with
      postoperative multidrug chemotherapy, the patient has shown objective disease
      regression for more than 11 months. However, it remains to be seen if disease
      regression will translate into increased survival.

PMID- 21181100
TI  - [On the article: "Psoriasis. Natural versus artificial balneophototherapy].

PMID- 21181101
TI  - [Cutaneous amyloidosis].
AB  - Amyloids are common protein aggregates in nature. Some amyloids fulfill important
      biological tasks while others are known to cause diseases. Despite the fact that
      the ultrastructure of amyloid is highly conserved, the mechanism of
      amyloidogenesis remains a challenging research topic. In humans, amyloidoses may
      develop in the skin or lead to skin signs due to secondary cutaneous involvement.
      An accurate diagnostic procedure is crucial for planning the therapy of this
      heterogeneous group of diseases. Therefore, the aim of this paper is to give an
      overview on the different kinds of amyloidoses as well as on diagnostic and
      therapeutic approaches. Furthermore, the discrimination between functional and
      disease-causing amyloid is briefly presented.

PMID- 21181102
TI  - [New surgical approaches for the treatment of anogenital HPV infections].
AB  - HPV infections in the anogenital region may have very heterogeneous clinical
      features. Most often typical papillomatous condylomata acuminata are observed
      that usually present no differential diagnostic difficulty. In contrast, the
      clinical findings of higher grade intraepithelial dysplasias with flat papules
      and erythematous/ eczematous lesions are often quite inconspicuous and hardly
      characteristic. The goal of therapy is to prevent further progression to
      carcinoma, removal of bothersome tumors and avoidance of complications. Surgical
      methods are preferentially employed for extensive lesions, unfavorable locations
      and higher grade dysplasia. Options include removal with scissors or scalpel,
      laser therapy and electrocautery. For purely intraepithelial alterations,
      superficial ablative techniques are usually preferable over excision. Further
      developments such as argon plasma coagulation reduce the risk of unwanted deep
      thermal destruction with the accompanying complications. The risks for the
      surgeon and the surgical team during treatment should also not be neglected. With
      consideration of all relevant aspects, the combination of different methods may
      reduce the risk of complications and frequency of recurrences. Due to the high
      recurrence rate independent of the selected therapy, consistent follow-up after
      primary therapy is crucial for the long-term success.

PMID- 21181103
TI  - [Atypical cutaneous infections with genital HPV].
AB  - Not only does genital "high risk HPV 16" play a significant role in cervical
      carcinomas, it is also the most commonly found mucosal virus in groups of well
      defined but atypical infections on the skin. In this group are included 1. Bowen
      disease, 2. squamous cell carcinomas on fingertips and nail units, 3. squamous
      cell carcinomas of eyelids and conjunctiva, 4. papillomas and squamous cell
      carcinoma of the external auditory canal. Bowen disease is a carcinoma in situ
      with a good prognosis and usually does not turn into a Bowen carcinoma. There is
      a close relation to genital high risk HPV, but integration of HPV 16 DNA into the
      cellular genome is rarely found in Bowen disease, and seems to appear only when
      there is a development into Bowen carcinoma. It is unclear how mucosal HPV infect
      the skin. Most authors assume that genito-digital inoculation occurs. However, in
      many cases of cutaneous Bowen disease there is no evidence of genital change and
      in most reported cases there is no immunosuppression. Similarly, in the case of
      rare carcinomas of fingers and nail units HPV 16 and HPV 16 - related types seem
      implicated. There is an almost universal assumption that infection here occurs
      via genital-digital contact. Immunosuppression, for example due to organ
      transplant or HIV infection, accelerates the emergence and spread of carcinomas.
      The mechanism of these types of carcinogenesis appears to be similar to that of
      the formation of cervical carcinomas. Although the central role in triggering
      carcinogenesis is played by persistent HPV infection, as is the case in cervical
      carcinoma, further factors must play a part, for example the condition of the
      immune system. Loss of immunological control can lead to a lasting proliferation
      of HPV infected cells. Additional factors such as UV light and toxic substances
      may enhance carcinogenesis, by lowering local tissue immunity and thus reducing
      intra-cellular control.

PMID- 21181104
TI  - [HPV-induced diseases].

PMID- 21181105
TI  - [What is palliative medicine?].

PMID- 21181106
TI  - [Complementary therapy in palliative medicine].
AB  - Even in the palliative context complementary therapy has a high value for
      patients and their relatives. In contrast to the methods of conventional medicine
      naturopathy as a holistic system has positive meanings for patients and their
      family. Complementary medicine in the palliative setting can be used as a
      supportive therapy in carefully selected cases. Doctors and patients should be
      careful regarding effect and side effects and should make sure that supportive
      therapy is given adequately and in effective doses. Complementary therapy should
      not be used in order to avoid the question of life and death. An adequate
      approach to the topic is mandatory, which acknowledges the needs of patients but
      also looks for their safety. Patients following alternative therapies sometimes
      neglect helpful therapeutic options. Carefully providing information on these
      therapies is mandatory. Physicians should avoid losing patients' confidence in
      their competence and attention in their final course of disease. Also in
      palliative medicine a sensitive approach to the topic of complementary medicine
      is mandatory, which accounts for the eligible wishes of patients and their
      relatives but puts the patients safety first.

PMID- 21181107
TI  - [Palliative medicine and advanced incurable illness].
AB  - Advanced incurable and life-threatening diseases of internal organs such as
      chronic obstructive pulmonary disease (COPD), heart failure, and terminal kidney
      failure are associated with considerable burden for the patients caused by
      pronounced symptoms (e.g., dyspnea, anxiety, depression) and unmet psychosocial
      needs. Nevertheless, in Germany addressing palliative medicine in the context of
      these disorders and co-treatment of these patients by cross-sector partnership
      with specialized palliative care physicians are not very developed. Against the
      background of an international perspective and current guidelines, general
      aspects of palliative care needs (symptom control, communication, advance care
      planning, etc.) are discussed together with the resultant implications for
      potential cooperation between internal medicine and palliative care as well as
      special aspects of the individual diseases (e.g., prognosis or implications of
      certain treatment options such as "automatic implantable cardioverter
      defibrillator", AICD). Timely involvement of the specific expertise of palliative
      care medicine can ensure that the workload of the primary providers (and their
      teams) is reduced and better cross-sector management (hospital and home) of the
      severely ill patients and their families is achieved.

PMID- 21181108
TI  - [Oncology and palliative medicine].
AB  - Approximately one half of patients who receive the diagnosis of cancer still die
      as the result of their disease. To be able to adequately meet the patients and
      their families needs, it is essential that oncologists and palliative care
      physicians cooperate closely. How the recommendations of international
      institutions are concerning the cooperation between the fields of oncology and
      palliative care medicine can be approached is exemplified by the concepts
      developed in the Center for Integrated Oncology (CIO Cologne/Bonn) at the
      University Hospital in Cologne and discussed critically.

PMID- 21181109
TI  - A structural intermediate between triisodontids and mesonychians (Mammalia,
      Acreodi) from the earliest Eocene of Portugal.
AB  - A new mammal, Mondegodon eutrigonus gen. et sp. nov., is described from the
      earliest Eocene locality of Silveirinha, Portugal. This species shows dental
      adaptations indicative of a carnivorous diet. M. eutrigonus is referred to the
      order Acreodi and considered, along with the early Paleocene North American
      species Oxyclaenus cuspidatus, as a morphological intermediate between two groups
      of ungulate-like mammals, namely, the triisodontids and mesonychians. Considering
      that triisodontids are early to early-late Paleocene North American taxa,
      Mondegodon probably belongs to a group that migrated from North America towards
      Europe during the first part of the Paleocene. Mondegodon could represent thus a
      relict genus, belonging to the ante-Eocene European mammalian fauna. The
      occurrence of such a taxon in Southern Europe may reflect a period of isolation
      of this continental area during the Paleocene/Eocene transition. In this context,
      the non-occurrence of closely allied forms of Mondegodon in the Eocene North
      European mammalian faunas is significant. This strengthens the hypothesis that
      the mammalian fauna from Southern Europe is characterized by a certain degree of
      endemism during the earliest Eocene. Mondegodon also presents some striking
      similarities with an unnamed genus from the early Eocene of India which could
      represent the first Asian known transitional form between the triisodontids and
      mesonychians.

PMID- 21181110
TI  - Age-related predictors of institutionalization: results of the German study on
      ageing, cognition and dementia in primary care patients (AgeCoDe).
AB  - BACKGROUND: In the last decades, many community-based studies have addressed
      predictors of nursing home placement (NHP) among the elderly. So far, predictors
      have not been analyzed separately for different age groups. METHODS: For a German
      GP-sample of 3,208 subjects aged 75 years and older, socio-demographic, clinical,
      and psychometric parameters were requested every 1.5 years over three waves.
      Logistic regression models determined predictors of NHP for total sample and for
      two different age groups. A CART analysis identified factors discriminating best
      between institutionalized and non-institutionalized individuals. RESULTS: Of the
      overall sample, 4.7% of the sample (n = 150) was institutionalized during the
      study period. Baseline characteristics associated with a higher risk of NHP for
      the total sample were age, living without spouse, cognitive and functional
      impairment and depression. In the CART analysis, age was the major discriminator
      at the first level (at age 81). In subgroup regression analyses, for the younger
      elderly (age 75-81) being single as well as cognitive and functional impairment
      increased the risk of NHP; in the advanced elderly (age 82+) being widowed and
      subjective memory impairment were significant predictors for NHP, and cognitive
      and functional impairment became non-significant as predictors of NHP.
      CONCLUSIONS: Predictors of NHP may differ in old age groups. The fact that many
      predictors show inconsistent results as predictors of NHP in the international
      literature may be attributed to the lack of differentiation in age groups.

PMID- 21181111
TI  - Suicidal behaviour and psychosocial problems in veterinary surgeons: a systematic
      review.
AB  - PURPOSE: Rates of suicide are elevated among veterinary surgeons in several
      countries, yet little is known about contributory factors. We have conducted a
      systematic review of studies investigating suicidal behaviour and psychosocial
      problems in veterinary surgeons. METHODS: A systematic search of the
      international research literature was performed in May 2008. Data from 52 studies
      of non-fatal suicidal behaviour, mental health difficulties, stress and burnout,
      occupational difficulties, and psychological characteristics of veterinary
      surgeons were extracted by two independent reviewers and analysed. Studies were
      rated for quality and greater emphasis placed on findings from higher quality
      studies. RESULTS: The majority of studies were of stress and occupational
      difficulties experienced by veterinary surgeons. Occupational stressors included
      managerial aspects of the job, long working hours, heavy workload, poor work-life
      balance, difficult client relations, and performing euthanasia. Few studies
      investigated suicidal behaviour or mental health difficulties in the profession.
      Some studies suggested that young and female veterinarians are at greatest risk
      of negative outcomes such as suicidal thoughts, mental health difficulties, and
      job dissatisfaction. CONCLUSIONS: The review highlights the difficulties faced by
      veterinary surgeons that may contribute to poor mental wellbeing and suicidal
      behaviour. Future research might include further examination of the influence of
      euthanasia on attitudes towards suicide and more direct examination of the impact
      that occupational risk factors might have on suicidal behaviour. Suggestions
      about the review's implications for suicide prevention in this group are also
      made.

PMID- 21181112
TI  - Prevalence and childhood antecedents of depersonalization syndrome in a UK birth
      cohort.
AB  - PURPOSE: Depersonalization syndrome is characterised by a sense of unreality
      about the self [depersonalization (DP)] and/or the outside world [derealization
      (DR)]. Prevalence estimates vary widely. Little is known about childhood
      antecedents of the disorder although emotional abuse is thought to play a role.
      METHODS: Longitudinal data from 3,275 participants of a UK population-based birth
      cohort (the MRC National Survey of Health and Development) were used to: (1)
      assess the prevalence of DP syndrome at age 36, measured by the Present State
      Examination (PSE); and (2) examine the effects of a range of socio-demographic,
      childhood adversity and emotional responses as potential risk factors for DP.
      RESULTS: Thirty three survey members were classified with DP, yielding a
      prevalence of 0.95% [95% confidence intervals (CI) 0.56-1.34]. There were no
      associations with socio-economic status, parental death or divorce; self-reported
      accidents, childhood depression, tendency to daydream or reactions to criticism.
      However, teacher-estimated childhood anxiety was a strong independent predictor
      of adult depersonalization, and there were strong cross-sectional relationships
      between DP and anxiety and depression caseness. CONCLUSIONS: To our knowledge
      this is the first study assessing nationwide prevalence of the DP syndrome and
      uses longitudinal data to explore childhood risk factors for adult DP. The
      prevalence of adult DP was slightly lower than reported by other surveys. The
      study found that childhood anxiety was the only significant predictor of the
      adult DP syndrome, supporting the view that depersonalisation disorder forms part
      of the spectrum of responses to anxiety.

PMID- 21181113
TI  - Hexavalent chromium reduction by Bacillus sp. strain FM1 isolated from heavy
      metal contaminated soil.
AB  - A Cr(VI) reducing bacterial strain FM1 was isolated from heavy metal contaminated
      agricultural soil irrigated with tannery effluents of Jajmau, Kanpur (India), and
      was identified as Bacillus sp. on the basis of biochemical methods and 16S rDNA
      gene sequence analysis. FM1 strain was found to be resistant to some toxic heavy
      metals (Cr(VI), Cr(III), Cu2+, Co2+, Cd2+, Ni2+ and Zn2+) up to several fold
      concentrations to the normal levels occurring in highly polluted region. FM1 was
      resistant to very high concentration of Cr(VI) (1,000 mg/L) and completely
      reduced 100 mg/L Cr(VI) within 48 h. Factors (pH, temperature, initial Cr(VI)
      concentration) affecting Cr(VI) reduction under culture condition were also
      evaluated. Reduction was optimum at 37  degrees C and pH 8. Cr(VI) reduction was
      enhanced by addition of glucose. The presence of heavy metal cations, such as
      Cu2+, Co2+, Cd2+, Ni2+ and Zn2+ showed differential effect on reduction. Since
      strain FM1 could grow in the presence of significant concentrations of metals and
      due to high Cr(VI) reduction ability, this bacterium may be potentially
      applicable in Cr(VI) detoxification.

PMID- 21181114
TI  - Determination of pesticide residues in rice grain by solvent extraction, column
      cleanup, and gas chromatography-electron capture detection.
AB  - A simple, easy, cheap and efficient analytical method for determination of
      multiple pesticide residues including organochlorine, organophosphorus, synthetic
      pyrethroids and herbicides in rice grain by capillary gas chromatography is
      developed. The quantification of residues was done by capillary gas
      chromatography with a MU-ECD detector and a HP-5MS capillary column. Known
      amounts of a mixture of pesticides were added to grain prior to extraction,
      cleanup and GC-determination. Recoveries were checked at two fortification
      levels; 0.1 and 0.5 MUg/g. Qualitative and quantitative analysis were carried out
      based on the retention time and peak area basis. The results show that the
      average recovery of the analytical method for the fortified rice samples was in
      the range of 74%-111% and %RSD in the range of 2.41-12.42. The analytical method
      was used to analyze commercial rice grain samples.

PMID- 21181115
TI  - Anti-inflammatory effects of limb ischaemic preconditioning are mediated by
      sensory nerve activation in rats.
AB  - We have shown that ischaemic preconditioning ameliorates both the local
      periosteal and the systemic leukocyte activation evoked by limb ischaemia
      reperfusion. We hypothesized that the activation of chemosensitive afferent
      nerves by transient ischaemia contributes to the protective mechanisms of
      ischaemic preconditioning via a calcitonin gene-related peptide (CGRP)-dependent
      mechanism. In Sprague-Dawley rats, 60-min complete limb ischaemia was followed by
      180 min of reperfusion. In further experiments, the CGRP analogue hCGRP (0.3 MUg
      kg(-1)) or ischaemic preconditioning (2 * 10-min ischaemia/10-min reperfusion)
      was applied prior to the ischaemia-reperfusion insult. Ischaemic preconditioning
      was performed in three subgroups in which animals received the CGRP receptor
      antagonist CGRP(8-37) (30 MUg kg(-1) h(-1)), the chemosensitive afferent nerve
      inactivator resiniferatoxin (3 * 15 MUg kg(-1), sc), or vehicle. The effects of
      CGRP(8-37) and resiniferatoxin on ischaemia-reperfusion without ischaemic
      preconditioning were also evaluated. In the tibial periosteum of rats, intravital
      fluorescence microscopy and immunohistochemistry revealed significant
      attenuations of ischaemia-reperfusion-induced post-ischaemic leukocyte
      endothelial interactions (rolling and adherence in the postcapillary venules) and
      tissue intracellular adhesion molecule expression following ischaemic
      preconditioning or hCGRP administration. Administration of CGRP(8-37) or
      pretreatment of animals with resiniferatoxin reversed the anti-inflammatory
      effects of limb ischaemic preconditioning, but failed to affect the
      microcirculatory consequences of ischaemia-reperfusion without ischaemic
      preconditioning. The results suggest that activation of the chemo- (capsaicin-)
      sensitive afferent nerves is involved in the mechanisms of microcirculatory anti
      inflammatory protection provided by limb ischaemic preconditioning. Controlled
      activation of chemosensitive C-fibres or the CGRP receptors by the induction of
      ischaemic preconditioning or other means may furnish therapeutic benefit by
      ameliorating the periosteal microcirculatory consequences of tourniquet
      ischaemia.

PMID- 21181116
TI  - Regulation of opioid gene expression in the rat brainstem by 3,4
      methylenedioxymethamphetamine (MDMA): role of serotonin and involvement of CREB
      and ERK cascade.
AB  - The amphetamine analogue 3,4-methylendioxymetamphetamine (MDMA, Ecstasy) causes
      complex adaptations at the molecular and cellular levels altering the activity of
      different brain neurotransmitters. The present study aims to verify the effects
      of single and repeated injections of MDMA on dynorphin and nociceptin systems
      gene regulation in the brainstem, an area rich in neurons containing serotonin.
      Both acute and chronic (twice a day for 7 days) MDMA (8 mg/kg) induced a marked
      increase in prodynorphin mRNA levels as well as in cAMP response element-binding
      protein (CREB) and extracellular signal-regulated kinase-1/2 (ERK1/2)
      phosphorylation, without causing any effect on kappa opioid receptor or
      nociceptin system (both pronociceptin and its receptor) genes expression, in this
      brain region. The blockade of 5HT1/5HT2 receptors by methysergide abolished the
      acute MDMA-induced increase in prodynorphin. Moreover, the concomitant chronic
      administration of both methysergide and MDMA (7 days) induced a significant
      increase in all the dynorphin or nociceptin system genes expression and in CREB
      and ERK phosphorylation. Our data suggest the involvement of dynorphin in the
      effects evoked by MDMA in the brainstem, possibly via CREB and ERK1/2 cascade
      activation, since the ERK inhibitor PD98059 prevented the MDMA-induced
      prodynorphin gene expression, and, acutely, also through the involvement of
      serotoninergic mechanisms. Chronically, it is also possible to hypothesize a
      general inhibitor role of serotonin in the effects evoked by MDMA. Moreover,
      these findings strengthen the hypothesis, already proposed, of a neuroprotective
      role for both CREB and dynorphin.

PMID- 21181117
TI  - Antidepressant response to chronic citalopram treatment in eight inbred mouse
      strains.
AB  - RATIONALE: The antidepressant response exhibits a characteristic delay. BALB/cJ
      mice respond to chronic, but not subchronic, treatment with selective serotonin
      reuptake inhibitors (SSRIs), providing a model of antidepressant onset.
      Identification of other mouse strains exhibiting this phenotype will provide
      additional tools for studying mechanisms of the antidepressant response.
      OBJECTIVES: We aimed to identify inbred mouse strains that respond to chronic,
      but not subchronic, SSRI treatment in the forced swim test (FST). We also
      assessed whether response correlated with genotype at the functional C1473G
      polymorphism in tryptophan hydroxylase-2 (Tph2). METHODS: BALB/cJ, three closely
      related strains (BALB/cByJ, SEA/GnJ, A/J), and four distantly related strains
      (C57BL/6J, C57BL/10J, CAST/EiJ, SM/J) received the SSRI citalopram (0-30
      mg/kg/day in drinking water) for ~4 weeks and were assessed for locomotion and
      FST behavior. Citalopram-responsive strains were assessed identically following
      ~1 week of treatment. C1473G genotypes were determined. RESULTS: BALB/cJ and
      related strains carried the 1473G allele and responded to chronic citalopram
      treatment in the FST. BALB/cJ, BALB/cByJ, and SEA/GnJ mice showed either no
      response or an attenuated response to subchronic treatment. Distantly related
      strains carried the 1473C allele and showed no response to citalopram. No
      relationship was found between the antidepressant response and baseline
      immobility or locomotion. CONCLUSIONS: BALB/cJ and related strains exhibit an
      antidepressant response to chronic SSRI treatment that emerges over time and is
      likely a heritable trait. This antidepressant response is associated with
      carrying the 1473G allele in Tph2. In conclusion, BALB/cJ and related strains
      provide valuable models for studying the therapeutic mechanisms of SSRIs.

PMID- 21181118
TI  - Serotonin revisited.

PMID- 21181120
TI  - Chronic treatment with fluoxetine prevents the return of extinguished auditory
      cued conditioned fear.
AB  - RATIONALE: We have recently shown that post-extinction exposure of rats to a sub
      threshold reminder shock can reactivate extinguished context-related freezing and
      found that chronic treatment with fluoxetine before fear extinction prevents this
      phenomenon. OBJECTIVES: In the present study, we examined whether these findings
      would be confirmed with auditory fear conditioning. METHODS: Rats were initially
      submitted to a session of five tone-shock pairings with either a 0.7- or 0.1-mA
      shock and underwent, 3 days later, a session of 20 tone-alone trials. RESULTS: At
      the beginning of this latter session, we observed cue-conditioned freezing in
      rats that received the strong, but not the weak, shock. At the end, both groups
      (strong and weak shocks) displayed similar low levels of freezing, indicating
      fear extinction in rats exposed to the strong shock. These rats exhibited again
      high levels of cue-evoked freezing when exposed to three tone-shock pairings with
      0.1-mA shock. This reemergence of cue-conditioned fear was completely abolished
      by chronic (over a 21-day period) fluoxetine treatment which spared, when
      administered before the initial fear conditioning, the original tone-shock
      association. CONCLUSIONS: These data extend our previous findings and suggest
      that chronic fluoxetine treatment favor extinction memory by dampening the
      reactivation of the original tone-shock association.

PMID- 21181121
TI  - Early continuous inhibition of group 1 mGlu signaling partially rescues dendritic
      spine abnormalities in the Fmr1 knockout mouse model for fragile X syndrome.
AB  - RATIONALE: Abnormal dendritic spine morphology is a significant neuroanatomical
      defect in fragile X mental retardation. It has been suggested that overactive
      group 1 metabotropic glutamate receptor (mGlu) signaling is associated with the
      spine dysmorphology occurring in fragile X syndrome (FXS). Thus, group 1 mGlu
      became a new therapeutic target for the treatment of FXS. OBJECTIVE: The purpose
      of this study was to identify the effect of inhibition of mGlu signaling in FXS.
      METHODS: We observed the changes in dendritic spines after pharmacological
      modulation of mGlu signaling in an Fmr1 knockout (KO) mouse model. RESULTS: The
      activation of group 1 mGlu resulted in elongation of dendritic spines in the
      cultured neurons derived from Fmr1 KO mice and wild-type (WT) mice. Antagonism of
      group 1 mGlu reduced the average spine length of Fmr1 KO neurons. Furthermore,
      systemic administration of the selective group 1 mGlu5 antagonist 2-methyl-6
      phenylethynyl pyridine (MPEP) reduced the average spine length and density in the
      cortical neurons of Fmr1 KO mice at developmental age. For the adult mice, MPEP
      administration was less effective for the restoration of spine length. The
      percentage of immature spines showed a similar reduction in parallel to the
      changes of spine length. Temporary MPEP intervention with single-dose treatment
      did not show any effect. CONCLUSION: These results show that MPEP administration
      could partially rescue the morphological deficits of dendritic spines in Fmr1 KO
      mice at developmental age.

PMID- 21181122
TI  - Modulation of neuroplastic molecules in selected brain regions after chronic
      administration of the novel antidepressant agomelatine.
AB  - RATIONALE: Neuronal plasticity is associated with depression, probably as a
      result of modified expression of proteins important for cellular resiliency. It
      is therefore important to establish if and how antidepressant drugs may be able
      to regulate these mechanisms in order to achieve relevant clinical effects.
      OBJECTIVE: We investigated the effects of chronic treatment with agomelatine (an
      MT(1)/MT(2) receptor agonist and 5-HT(2C) receptor antagonist) on the brain
      derived neurotrophic factor (BDNF), fibroblast growth factor (FGF-2), and
      activity-regulated cytoskeleton-associated protein (Arc). METHODS: Animals were
      treated for 21 days with agomelatine, venlafaxine, or a vehicle and sacrificed 1
      h (6 p.m.) or 16 h after the last injection (9 a.m.) to evaluate the messenger
      RNA (mRNA) and protein expression of these neuroplastic markers in the
      hippocampus and prefrontal cortex. RESULTS: Agomelatine, but not venlafaxine,
      produced major transcriptional changes in the hippocampus, where significant up
      regulations of BDNF and FGF-2 were observed. Both drugs up-regulated the Arc
      transcription levels. No effects were observed in the prefrontal cortex. Instead,
      the levels of BDNF protein were elevated by agomelatine in both regions: the
      effects of the drug on mRNA levels in the hippocampus and cortex are different,
      while the effects on the protein seem to have the same cumulative result,
      suggesting different modulatory mechanisms in the two regions. CONCLUSIONS: Our
      data provide new information regarding the molecular mechanisms that contribute
      to the chronic effects of the new antidepressant agomelatine on brain function.
      The ability of agomelatine to modulate the expression of these neuroplastic
      molecules, which follows a circadian rhythm, may contribute to its antidepressant
      action.

PMID- 21181123
TI  - Selective blockade of the orexin-2 receptor attenuates ethanol self
      administration, place preference, and reinstatement.
AB  - RATIONALE: Orexin-1 receptor antagonists have been shown to block the reinforcing
      effects of drugs of abuse and food. However, whether blockade of orexin-2
      receptor has similar effects has not been determined. We have recently described
      the in vitro and in vivo effects of JNJ-10397049, a selective and brain penetrant
      orexin-2 receptor antagonist. OBJECTIVE: The goal of these studies was to
      evaluate whether systemic administration of JNJ-10397049 blocks the rewarding
      effects of ethanol and reverses ethanol withdrawal in rodents. As a comparison,
      SB-408124, a selective orexin-1 receptor antagonist, was also evaluated. METHODS:
      Rats were trained to orally self-administer ethanol (8% v/v) or saccharin (0.1%
      v/v) under a fixed-ratio 3 schedule of reinforcement. A separate group of rats
      received a liquid diet of ethanol (8% v/v) and withdrawal signs were evaluated 4
      h after ethanol discontinuation. In addition, ethanol-induced increases in
      extracellular dopamine levels in the nucleus accumbens were tested. In separate
      experiments, the acquisition, expression, and reinstatement of conditioned place
      preference (CPP) were evaluated in mice. RESULTS: Our results indicate that JNJ
      10397049 (1, 3, and 10 mg/kg, sc) dose-dependently reduced ethanol self
      administration without changing saccharin self-administration, dopamine levels,
      or withdrawal signs in rats. Treatment with JNJ-10397049 (10 mg/kg, sc)
      attenuated the acquisition, expression, and reinstatement of ethanol CPP and
      ethanol-induced hyperactivity in mice. Surprisingly, SB-408124 (3, 10 and 30
      mg/kg, sc) did not have any effect in these procedures. CONCLUSIONS:
      Collectively, these results indicate, for the first time, that blockade of orexin
      2 receptors is effective in reducing the reinforcing effects of ethanol.

PMID- 21181125
TI  - T-pattern analysis of diazepam-induced modifications on the temporal organization
      of rat behavioral response to anxiety in hole board.
AB  - RATIONALE: By means of t-pattern analysis, it has been observed that the
      different events, characterizing rat behavior in hole board (HB), present close
      interrelationships which occur sequentially and with significant constraints on
      the interval lengths separating them. OBJECTIVES: The aim of present research was
      to study, by means of descriptive and multivariate t-pattern analyses, the
      effects of the reference anxiolytic drug diazepam (DZP) on temporal structure of
      a rat's anxiety-related behavior in HB. METHODS: Fifty-six male Wistar rats were
      tested for 10 min in HB. Video files, collected for each animal, were coded by
      means of a software coder, and event log files, generated for each subject, were
      analyzed by means of a specific software for temporal pattern analysis (t-pattern
      analysis). RESULTS: Significant diazepam-induced modifications were observed for
      durations of walking, climbing, edge-sniff, and face grooming. Dose-dependent
      decreases of t-patterns' total amount, of their mean occurrences and of their
      mean length for each group were detected. Also, t-patterns' mean occurrences, in
      terms of different composition, were reduced. Percent distributions showed a
      significant increase of t-patterns including walking for all administered groups,
      and significant reductions of t-patterns including climbing, immobile sniffing,
      and edge-sniff. Front-paw licking and face grooming were reduced at the higher
      DZP dose. CONCLUSIONS: Present study demonstrates, for the first time, that the
      temporal structure of Wistar rats' behavioral response to anxiety in HB changes
      following pharmacological manipulation of anxiety condition. Moreover, t-pattern
      analysis is suggested to represent a useful tool to evaluate and compare
      different classes of anti-anxiety molecules.

PMID- 21181124
TI  - AVE1625, a cannabinoid CB1 receptor antagonist, as a co-treatment with
      antipsychotics for schizophrenia: improvement in cognitive function and reduction
      of antipsychotic-side effects in rodents.
AB  - RATIONALE: The psychotomimetic effects of cannabis are believed to be mediated
      via cannabinoid CB1 receptors. Furthermore, studies have implicated CB1 receptors
      in the pathophysiology of schizophrenia. OBJECTIVE: These studies investigated
      the effects of the CB1 receptor antagonist, AVE1625, in acute pharmacological and
      neurodevelopmental models of schizophrenia. AVE1625 was administered to rodents
      alone or as a co-treatment with clinically used antipsychotic drugs (APDs).
      METHODS: The antipsychotic potential of AVE1625 was tested using psychotomimetic
      induced hyperactivity and latent inhibition (LI) deficit models. The procognitive
      profile was assessed using hole board, novel object recognition, auditory evoked
      potential, and LI techniques. In addition, the side-effect profile was
      established by measuring catalepsy, antipsychotic-induced weight gain, plasma
      levels of prolactin, and anxiogenic potential. RESULTS: AVE1625 (1, 3, and 10
      mg/kg ip), reversed abnormally persistent LI induced by MK-801 or neonatal nitric
      oxide synthase inhibition in rodents, and improved both working and episodic
      memory. AVE1625 was not active in positive symptom models but importantly, it did
      not diminish the efficacy of APDs. It also decreased catalepsy and weight gain
      induced by APDs, suggesting that it may decrease APD-induced extrapyramidal side
      effects (EPS) and compliance. Unlike other CB1 antagonists, AVE1625 did not
      produce anxiogenic-like effects. CONCLUSIONS: These preclinical data suggest that
      AVE1625 may be useful to treat the cognitive deficits in schizophrenia and as a
      co-treatment with currently available antipsychotics. In addition, an improved
      side-effect profile was seen, with potential to ameliorate the EPS and weight
      gain issues with currently available treatments.

PMID- 21181126
TI  - Fluoxetine reverses the memory impairment and reduction in proliferation and
      survival of hippocampal cells caused by methotrexate chemotherapy.
AB  - RATIONALE: Adjuvant cancer chemotherapy can cause long-lasting, cognitive
      deficits. It is postulated that these impairments are due to these drugs
      targeting neural precursors within the adult hippocampus, the loss of which has
      been associated with memory impairment. OBJECTIVES: The present study
      investigates the effects of the chemotherapy, methotrexate (MTX) on spatial
      working memory and the proliferation and survival of the neural precursors
      involved in hippocampal neurogenesis, and the possible neuroprotective properties
      of the antidepressant fluoxetine. METHODS: Male Lister hooded rats were
      administered MTX (75 mg/kg, two i.v. doses a week apart) followed by leucovorin
      rescue (i.p. 18 h after MTX at 6 mg/kg and at 26, 42 and 50 h at 3 mg/kg) and/or
      fluoxetine (10 mg/kg/day in drinking water for 40 days). Memory was tested using
      the novel location recognition (NLR) test. Using markers, cell proliferation
      (Ki67) and survival (bromodeoxyuridine/BrdU), in the dentate gyrus were
      quantified. RESULTS: MTX-treated rats showed a cognitive deficit in the NLR task
      compared with the vehicle and fluoxetine-treated groups. Cognitive ability was
      restored in the group receiving both MTX and fluoxetine. MTX reduced both the
      number of proliferating cells in the SGZ and their survival. This was prevented
      by the co-administration of fluoxetine, which alone increased cell numbers.
      CONCLUSIONS: These results demonstrate that MTX induces an impairment in spatial
      working memory and has a negative long-term effect on hippocampal neurogenesis,
      which is counteracted by the co-administration of fluoxetine. If translatable to
      patients, this finding has the potential to prevent the chemotherapy-induced
      cognitive deficits experienced by many cancer survivors.

PMID- 21181127
TI  - Repeated administration of the GABAB receptor positive modulator BHF177 decreased
      nicotine self-administration, and acute administration decreased cue-induced
      reinstatement of nicotine seeking in rats.
AB  - RATIONALE: gamma-Aminobutyric acid (GABA) is the major inhibitory
      neurotransmitter in the brain and is implicated in the modulation of central
      reward processes. Acute or chronic administration of GABA(B) receptor agonists or
      positive modulators decreased self-administration of various drugs of abuse.
      Furthermore, GABA(B) receptor agonists inhibited cue-induced reinstatement of
      nicotine- and cocaine-seeking behavior. Because of their fewer adverse side
      effects compared with GABA(B) receptor agonists, GABA(B) receptor positive
      modulators are potentially improved therapeutic compounds for the treatment of
      drug dependence compared with agonists. OBJECTIVES AND METHODS: We examined
      whether the acute effects of the GABA(B) receptor positive modulator N
      [(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-2-methyl-5-[4-(trifluoromethyl)phenyl]-4
      pyrimidinamine (BHF177) on nicotine self-administration and food-maintained
      responding under a fixed-ratio 5 schedule of reinforcement were maintained after
      repeated administration. The effects of acute BHF177 administration on cue
      induced nicotine- and food-seeking behavior, a putative animal model of relapse,
      were also examined. RESULTS: Repeated administration of BHF177 for 14 days
      decreased nicotine self-administration, with small tolerance observed during the
      last 7 days of treatment, whereas BHF177 minimally affected food-maintained
      responding. Acute BHF177 administration dose-dependently blocked cue-induced
      reinstatement of nicotine-, but not food-, seeking behavior after a 10-day
      extinction period. CONCLUSIONS: These results showed that BHF177 selectively
      blocked nicotine self-administration and prevented cue-induced reinstatement of
      nicotine seeking, with minimal effects on responding for food and no effect on
      cue-induced reinstatement of food seeking. Thus, GABA(B) receptor positive
      modulators could be useful therapeutics for the treatment of different aspects of
      nicotine dependence by facilitating smoking cessation by decreasing nicotine
      intake and preventing relapse to smoking in humans.

PMID- 21181128
TI  - Growth hormone responses to GABAB receptor challenge with baclofen and
      impulsivity in healthy control and personality disorder subjects.
AB  - BACKGROUND: The role of abnormal GABAergic neural transmission in impulsive
      aggression is not well understood. We have previously shown that central levels
      of GABA are positively correlated with impulsivity in adult humans with and
      without personality disorder. An important regulator of GABAergic function is the
      GABA(B) receptor, a presynaptic autoreceptor and heteroreceptor. GABA(B) receptor
      sensitivity may be tested by measuring the growth hormone response to the
      receptor-agonist baclofen. The purpose of this investigation is to test the
      hypothesis that dimensional measures of impulsivity and impulsive aggression are
      negatively correlated with growth hormone response. METHODS: Twenty healthy
      volunteers (without Axis I or II disorder) and 20 personality-disordered subjects
      (meeting DSM-IV general criteria for personality disorder) underwent challenge
      with 20 mg baclofen administered orally, followed by a time series of blood
      samples for measure of growth hormone response analyzed by repeated measures
      ANOVA. RESULTS: An expected significant effect for drug and drug * time
      interaction verified that baclofen caused a surge in growth hormone level. There
      was no effect of group (healthy volunteer or personality disorder) or interaction
      with group on the time series or peak growth hormone response. As hypothesized,
      peak growth hormone response was negatively correlated with impulsivity as
      measured by the Barratt Impulsivity Scale (BIS-11; r = -0.39, n = 37, p < 0.02).
      The relationship remained significant when examining the healthy volunteer and
      personality disorder groups separately, indicating that the relationship with
      impulsivity was not merely due to the presence or absence of personality
      disorder. The relationship with impulsive aggression was only at a trend level of
      significance. CONCLUSION: The magnitude of growth hormone response to baclofen,
      an index of GABA(B) receptor function, was negatively correlated with a
      dimensional measure impulsivity, but not related to the categorical diagnosis of
      personality disorder. Further work is necessary to understand how GABAergic
      dysfunction may play a role in impulsive aggression.

PMID- 21181129
TI  - Second-generation antidepressants in social anxiety disorder: meta-analysis of
      controlled clinical trials.
AB  - RATIONALE: A growing number of controlled clinical trials suggest that different
      second-generation antidepressants (SGA) may be effective in the treatment of
      social anxiety disorder (SAD). OBJECTIVES: The aim of the present study is to
      evaluate the effectiveness of SGA in SAD and to investigate possible differences
      in their efficacy. METHODS: We performed a systematic review and meta-analysis of
      all double-blind, randomized, controlled clinical trials involving second
      generation antidepressants in adult patients with SAD published on
      PubMed/MEDLINE, PsycINFO, and Current Controlled Trials databases until July
      2009. Our analyses were based on changes in Liebowitz Social Anxiety Scale
      (LSAS), Clinical Global Impression (CGI), and standardized mean difference (SMD).
      RESULTS: Twenty-seven controlled clinical trials, comprising ten different SGA,
      were selected. When comparing the reduction of LSAS scores, the group receiving
      active drugs showed a significantly greater reduction compared to those observed
      in the placebo group [pooled weighted mean -11.9 (IC 95% -14.5 to -9.4)]. The
      combined relative risk (RR) for the different drugs revealed a 62% increase in
      treatment response (final CGI <=2) for those using SGAs, compared to those
      receiving placebo [RR 1.62 (95% CI 1.44-1.81)]. The combined SMD for the SGAs was
      -0.43 (IC 95% -0.49 to -0.37). CONCLUSION: Second-generation antidepressants are
      efficacious treatment for patients with SAD. However, our results do not suggest
      differences of efficacy among different drugs.

PMID- 21181130
TI  - Oral cortisol impairs implicit sequence learning.
AB  - RATIONALE: Glucocorticoids have been shown to affect declarative memory, an
      explicit form of memory for facts and events operated by medial temporal lobe
      structures. Recent neuroimaging data suggest that the medial temporal lobe
      (including the hippocampus) is also active in implicit sequence learning.
      OBJECTIVES: The aim of the present study was to investigate whether implicit
      sequence learning may also be affected by glucocorticoid administration. METHODS:
      Oral cortisol (30 mg) was given to 29 healthy subjects whereas 31 control
      subjects received placebo. One hour after treatment all volunteers performed five
      consecutive blocks of a five-choice serial reaction time task by responding to
      colored lights by pressing buttons of the same color. The subjects responded
      without knowing to a quasi-randomized stimulus sequence, including higher-order
      sequential regularities (a combination of two colors that predicted the following
      target color). The reaction speed of every button-press (100 per block) was
      determined and difference scores were calculated as a proof of learning. RESULTS:
      Both groups showed significant implicit sequence learning throughout the
      experiment. However, we found an impaired learning performance of the cortisol
      group compared with the placebo group. Further analysis revealed that a delayed
      learning in the cortisol group occurred at the very beginning of the task.
      CONCLUSIONS: This study is the first human investigation indicating impaired
      implicit memory function after exogenous administration of the stress hormone
      cortisol. This effect may depend on hippocampus engagement in implicit sequence
      learning, but the involvement of other brain structures is also discussed.

PMID- 21181131
TI  - Effects of delta opioid receptors activation on a response inhibition task in
      rats.
AB  - RATIONALE: Response inhibition, a primary symptom of many psychiatric disorders,
      is mediated through a complex neuropharmacological network that involves
      dopamine, serotonin, glutamate, noradrenaline, and cannabinoid mechanisms.
      Recently, we identified an opioidergic contribution to response inhibition by
      showing that deletion of mu or delta opioid receptors in mice alters motor
      impulsivity. OBJECTIVES: We investigated this phenomenon further by testing
      whether pharmacological activation of opioid receptors disrupts the ability to
      inhibit a motor response. METHODS: Long-Evans rats were trained to withhold a
      lever-pressing response for sucrose until a discriminative stimulus (lever light)
      was presented. The delay to the discriminative stimulus (1 to 60 s) was varied,
      so animals could not predict, on any given trial, the length of the pre-response
      phase. Motor impulsivity was assessed as the inability to inhibit lever pressing
      prior to the discriminative stimulus. Rats were tested following an injection of
      the mu opioid receptor agonist morphine (0, 0.5, 1, 2, 4, 6, 8, or 10 mg/kg) or
      the delta receptor agonist SNC80 (0, 2.5, 5, or 10 mg/kg). RESULTS: SNC80 (10
      mg/kg) increased premature responses and locomotor activity, but had no effect on
      the speed of responding or non-reinforced presses. The SNC80-induced decrease in
      accuracy was blocked by the delta opioid receptor antagonist naltrindole.
      Morphine had no effect on accuracy but increased locomotor activity (2 mg/kg).
      CONCLUSIONS: These findings point to a role for delta, but not mu, opioid
      receptors in disinhibition as measured in the response inhibition task. The
      results appear to contradict those of previous opioid receptor deletion studies;
      possible sources of these discrepant results are discussed.

PMID- 21181133
TI  - Real-time electrical impedance-based measurement to distinguish oral cancer cells
      and non-cancer oral epithelial cells.
AB  - In this study, electrical impedance-based measurements were used to distinguish
      oral cancer cells and non-cancer oral epithelial cells based on their cellular
      activities on the microelectrodes in a real-time and label-free manner. CAL 27
      and Het-1A cell lines were used as the models of oral cancer cells and non-cancer
      oral epithelial cells, respectively. Various cellular activities, including cell
      adhesion, spreading, and proliferation were monitored. We found that both the
      kinetics of cell spreading and the static impedance-based cell index were
      feasible to distinguish the two cell types. At each given cell number, CAL 27
      cell spreading produced a smaller cell index change rate that was 60-70% of those
      of Het-1A cells. When cells were fully spread, CAL 27 cells generated a cell
      index more than four times greater than that of Het-1A cells. Since cell
      spreading and attachment occurs in the first few hours when they were cultured on
      the microelectrodes, this impedance-based method could be a rapid label-free and
      non-invasive approach to distinguish oral cancer cells from non-cancer oral
      epithelial cells. Cell viability analysis was performed along with the impedance
      based analysis. Confocal microscopic imaging analysis showed the difference in
      cell morphology and the thickness of cell monolayers between the two cell types.

PMID- 21181134
TI  - Chip electrophoresis of active banana ingredients with label-free detection
      utilizing deep UV native fluorescence and mass spectrometry.
AB  - In the present work, we report on a rapid and straightforward approach for the
      determination of biologically active compounds in bananas applying microchip
      electrophoresis (MCE). For this purpose, we applied label-free detection
      utilizing deep UV fluorescence detection with excitation at 266 nm. Using this
      approach, we could identify dopamine and serotonin, their precursors tryptophan
      and tyrosine and also the isoquinoline alkaloid salsolinol in less than 1 min. In
      bananas, after 10 days of ripening, we additionally found the compound levodopa
      which is a metabolite of the tyrosine pathway. Quantitative analysis of extracts
      by external calibration revealed concentrations of serotonin, tryptophan, and
      tyrosine from 2.7 to 7.6 MUg/mL with relative standard deviations of less than
      3.5%. The corresponding calibration plots showed good linearity with correlation
      coefficients higher than 0.985. For reliable peak assignment, the compounds were
      also analyzed by coupling chip electrophoresis with mass spectrometry. This paper
      demonstrates exemplarily the applicability of MCE with native fluorescence
      detection for rapid analysis of natural compounds in fruits and reveals the
      potential of chip-based separation systems for the analysis of complex mixtures.

PMID- 21181135
TI  - Formation of pyranoanthocyanins in red wines: a new and diverse class of
      anthocyanin derivatives.
AB  - Pyranoanthocyanins constitute one of the most important classes of anthocyanin
      derived pigments occurring naturally in red wine. Nonetheless, correct assignment
      of their structures and pathways of formation in red wine has been relatively
      recent--less than two decades. Study of these newly discovered pigments is
      progressively unfolding the chemical pathways that drive the evolution of red
      wine colour during ageing. The objective of this paper is to review current
      knowledge regarding the pathway of formation in red wine of a great variety of
      pyranoanthocyanin structures, namely carboxypyranoanthocyanins,
      methylpyranoanthocyanins, pyranoanthocyanin-flavanols, pyranoanthocyanin-phenols,
      portisins, oxovitisins, and pyranoanthocyanin dimers. The chromatic features of
      some of the compounds, for example their colour expression and acid-base
      equilibria in aqueous media, are also discussed.

PMID- 21181136
TI  - Capillary electrophoresis with electrochemiluminescence detection: fundamental
      theory, apparatus, and applications.
AB  - This review presents a comprehensive survey of recent progress on
      electrochemiluminescence (ECL) detection coupled with capillary electrophoresis
      (CE). The fundamental theories involved in CE-ECL, e.g., the mechanism involving
      both coreactant-based and inhibitor-based ECL, as well as the possible analytes
      to be detected by CE-ECL are summarized. Different schemes for the construction
      of CE-ECL apparatus, including methods for preparing the working electrode,
      approaches for addition of ECL reagents, ways to fabricate electrical decouplers,
      and factors affecting ECL efficiency are reviewed. Discussion of the literature
      related to the application of CE-ECL from January 2005 to September 2010 is
      sorted by the corresponding analyte matrixes, namely, the standard solution,
      urine, serum and plasma, and other matrixes. Finally, possible trends for CE-ECL
      in the near future are discussed.

PMID- 21181137
TI  - Size separations of starch of different botanical origin studied by asymmetrical
      flow field-flow fractionation and multiangle light scattering.
AB  - Asymmetrical-flow field-flow fractionation combined with multiangle light
      scattering and refractive index detection has been revealed to be a powerful tool
      for starch characterization. It is based on size separation according to the
      hydrodynamic diameter of the starch components. Starch from a wide range of
      different botanical sources were studied, including normal starch and high
      amylose and high-amylopectin starch. The starch was dissolved by heat treatment
      at elevated pressure in a laboratory autoclave. This gave clear solutions with no
      granular residues. Amylose retrogradation was prevented by using freshly
      dissolved samples. Programmed cross flow starting at 1.0 mL min(-1) and
      decreasing exponentially with a half-life of 4 min was utilised. The starches
      showed two size populations representing mainly amylose and mainly amylopectin
      with an overlapping region where amylose and amylopectin were possibly co-eluted.
      Most of the first population had molar masses below 10(6) g mol(-1), and most of
      the second size population had molar masses above 10(7) g mol(-1). Large
      differences were found in the relative amounts of the two populations, the molar
      mass, and hydrodynamic diameters, depending on the plant source and its
      varieties.

PMID- 21181138
TI  - Analysis of genetic variations in the dopamine D1 receptor (DRD1) gene and
      antipsychotics-induced tardive dyskinesia in schizophrenia.
AB  - BACKGROUND: Dyskinesia is a kind of abnormal involuntary movement disorder that
      increases with age. The pathogenesis of dyskinesia may result from divergent
      changes in dopamine D1 receptors (DRD1) and dopamine D2 receptors (DRD2) in the
      brain while aging. Tardive dyskinesia (TD), a kind of dyskinesia, may develop
      after long-term antipsychotic treatment. Because the prevalence of TD also
      steadily increased with age, TD has been suggested to be the consequence of an
      imbalance between DRD1 and DRD2. We supposed that patients who develop TD may
      have genetic variants of DRD1 that cause the excitatory effects of DRD1
      overwhelming the attenuated inhibitory effects of DRD2 after antipsychotic
      treatment. METHODS: In the present study, schizophrenic inpatients receiving long
      term antipsychotic treatment were first assessed using the Abnormal Involuntary
      Movement Scale (AIMS), and only patients who were either free of any abnormal
      involuntary movements (non-TD group, AIMS =0) or who showed persistent TD (TD
      group) were enrolled. Finally, 382 patients were recruited (TD=220, non-TD=162)
      and three single nucleus polymorphisms (SNPs; rs5326, rs4532 and rs265975) of
      DRD1 were genotyped for each subject. RESULTS: Genotype frequency (%; AA/AG/GG)
      of rs4532 (TD: non-TD) was 61.4/35.8/2.8: 74.2/24.5/1.3. After genetic analyses,
      genotype GG showed significant association with TD (if OR=2.0, power (%)=98.5; if
      OR=1.5, power (%)=63.7; P=0.033). Haplotype frequency (%) CGC of rs5326-rs4532
      rs265975 (TD: non-TD) was 19.0:13.7; and after haplotype-based analyses,
      haplotype CGC also showed significant association with TD (OR=1.4, permutation
      P=0.027). CONCLUSION: Our results indicate that the genotypic variants of DRD1
      might play a role in the susceptibility of TD. Further replication in other
      countries or other populations is highly expected.

PMID- 21181139
TI  - Lack of effect of hydrochlorothiazide and low-dose aspirin on the renal clearance
      of urate and oxypurinol after a single dose of allopurinol in normal volunteers.
AB  - AIMS: To determine whether low-dose aspirin and hydrochlorothiazide (HCTZ) affect
      the renal clearance of oxypurinol and/or urate. METHODS: Healthy volunteers (n =
      8) were treated with allopurinol (600 mg, control), and allopurinol (600 mg) co
      administered with single doses of aspirin (100 mg) or HCTZ (25 mg) or a
      combination of the two. RESULTS: Hydrochlorothiazide, low-dose aspirin or a
      combination of the two, when co-administered with allopurinol, did not
      significantly alter (P > 0.05) the renal clearance of oxypurinol or urate. In
      particular, aspirin and HCTZ, when taken together and with allopurinol, did not
      change (P > 0.05) oxypurinol fractional renal clearance (allopurinol alone:
      0.217, 0.173-0.262; combined: 0.202, 0.155-0.250) or urate fractional renal
      clearance (allopurinol alone: 0.066, 0.032-0.099; combined: 0.058, 0.038-0.078).
      CONCLUSIONS: A single, low-dose of aspirin or an anti-hypertensive dose of
      hydrochlorothiazide, when administered alone or together with allopurinol, are
      unlikely to alter the hypouricaemic effect of allopurinol. The effect of chronic
      aspirin and HCTZ dosing taken together upon the efficacy of chronic allopurinol
      therapy in patients with hyperuricaemia needs to be investigated.

PMID- 21181140
TI  - New year's greeting from the ESNR.

PMID- 21181141
TI  - A venographic operational classification for transvenous embolization of dural
      carotid-cavernous fistula.
AB  - INTRODUCTION: It is hypothesized that a venographic-based operational
      classification of dural carotid-cavernous fistula (DCCF) will facilitate early
      selection of the optimal venous route and enhance the efficacy of transvenous
      catheterization and embolization of the cavernous sinus. METHODS: This was a
      retrospective study on 97 patients who presented with symptomatic DCCF.
      Definition of classification type 1: both the anterior and posterior compartments
      of the cavernous sinus were opacified, type 2: only the anterior compartment was
      opacified, type 3: only the posterior compartment was opacified. Subtype a: the
      facial vein (FV) draining the superior ophthalmic vein (SOV) was opacified,
      subtype b: only the inferior petrosal sinus (IPS) was opacified, subtype c:
      neither the FV nor the IPS were opacified, subtype d: both the FV and the IPS
      were opacified. The SOV route was recommended for subtype 1a and type 2. The IPS
      route was recommended for subtype 1b, 1c, 1d, and type 3. Success rates of
      catheterization by the recommended routes and non-recommended routes were
      calculated. RESULTS: Number of DCCF lesions were 20 (1a), 28 (1b), 23 (1c), 26
      (1d), 16 (2a), 10 (2c), 2 (3b). Of 145 attempted catheterization, 91 and 54 were
      performed with a recommended route and un-recommended route, respectively.
      Success rate for catheterization and embolization performed with the recommended
      route and un-recommended route was 71/91 (78%) and 20/54 (37%), respectively (Chi
      Square test P = 0.0024). CONCLUSIONS: Venographic operational classification is
      useful for guiding the selection of optimal venous route which enhances the
      efficacy of transvenous embolization of the DCCF.

PMID- 21181142
TI  - Genotype is a stronger determinant than sex of the mouse gut microbiota.
AB  - The mammalian gut microbiota is considered to be determined mostly by diet, while
      the effect of genotype is still controversial. Here, we examined the effect of
      genotype on the gut microbiota in normal populations, exhibiting only natural
      polymorphisms, and evaluated this effect in comparison to the effect of sex. DNA
      fingerprinting approaches were used to profile the gut microbiota of eight
      different recombinant inbred mouse lines of the collaborative cross consortium,
      whose level of genetic diversity mimics that of a natural human population.
      Analyses based on automated ribosomal internal transcribed spacer analysis
      demonstrated significant higher similarity of the gut microbiota composition
      within mouse lines than between them or within same-gender groups. Thus, genetic
      background significantly impacts the microbiota composition and is a stronger
      determinant than gender. These findings imply that genetic polymorphisms help
      shape the intestinal microbiota of mammals and consequently could affect host
      susceptibility to diseases.

PMID- 21181143
TI  - Peptide model helices in lipid membranes: insertion, positioning, and lipid
      response on aggregation studied by X-ray scattering.
AB  - Studying membrane active peptides or protein fragments within the lipid bilayer
      environment is particularly challenging in the case of synthetically modified,
      labeled, artificial, or recently discovered native structures. For such samples
      the localization and orientation of the molecular species or probe within the
      lipid bilayer environment is the focus of research prior to an evaluation of
      their dynamic or mechanistic behavior. X-ray scattering is a powerful method to
      study peptide/lipid interactions in the fluid, fully hydrated state of a lipid
      bilayer. For one, the lipid response can be revealed by observing membrane
      thickening and thinning as well as packing in the membrane plane; at the same
      time, the distinct positions of peptide moieties within lipid membranes can be
      elucidated at resolutions of up to several angstroms by applying heavy-atom
      labeling techniques. In this study, we describe a generally applicable X-ray
      scattering approach that provides robust and quantitative information about
      peptide insertion and localization as well as peptide/lipid interaction within
      highly oriented, hydrated multilamellar membrane stacks. To this end, we have
      studied an artificial, designed beta-helical peptide motif in its homodimeric and
      hairpin variants adopting different states of oligomerization. These peptide
      lipid complexes were analyzed by grazing incidence diffraction (GID) to monitor
      changes in the lateral lipid packing and ordering. In addition, we have applied
      anomalous reflectivity using synchrotron radiation as well as in-house X-ray
      reflectivity in combination with iodine-labeling in order to determine the
      electron density distribution rho(z) along the membrane normal (z axis), and
      thereby reveal the hydrophobic mismatch situation as well as the position of
      certain amino acid side chains within the lipid bilayer. In the case of multiple
      labeling, the latter technique is not only applicable to demonstrate the
      peptide's reconstitution but also to generate evidence about the relative peptide
      orientation with respect to the lipid bilayer.

PMID- 21181144
TI  - GGDEF proteins YeaI, YedQ, and YfiN reduce early biofilm formation and swimming
      motility in Escherichia coli.
AB  - The second messenger 3'-5'-cyclic diguanylic acid (c-di-GMP) promotes biofilm
      formation, and c-di-GMP is synthesized by diguanylate cyclases (characterized by
      a GGDEF domain) and degraded by phosphodiesterases. Here, we evaluated the effect
      of the 12 E. coli GGDEF-only proteins on biofilm formation and motility.
      Deletions of the genes encoding the GGDEF proteins YeaI, YedQ, YfiN, YeaJ, and
      YneF increased swimming motility as expected for strains with reduced c-di-GMP.
      Alanine substitution in the EGEVF motif of YeaI abolished its impact on swimming
      motility. In addition, extracellular DNA (eDNA) was increased as expected for the
      deletions of yeaI (tenfold), yedQ (1.8-fold), and yfiN (3.2-fold). As a result of
      the significantly enhanced motility, but contrary to current models of decreased
      biofilm formation with decreased diguanylate cyclase activity, early biofilm
      formation increased dramatically for the deletions of yeaI (30-fold), yedQ (12
      fold), and yfiN (18-fold). Our results indicate that YeaI, YedQ, and YfiN are
      active diguanylate cyclases that reduce motility, eDNA, and early biofilm
      formation and contrary to the current paradigm, the results indicate that c-di
      GMP levels should be reduced, not increased, for initial biofilm formation so c
      di-GMP levels must be regulated in a temporal fashion in biofilms.

PMID- 21181145
TI  - Microbial production of polyhydroxyalkanoate block copolymer by recombinant
      Pseudomonas putida.
AB  - Polyhydroxyalkanoate (PHA) synthesis genes phaPCJ(Ac) cloned from Aeromonas
      caviae were transformed into Pseudomonas putida KTOY06DeltaC, a mutant of P.
      putida KT2442, resulting in the ability of the recombinant P. putida KTOY06DeltaC
      (phaPCJ(A.c)) to produce a short-chain-length and medium-chain-length PHA block
      copolymer consisting of poly-3-hydroxybutyrate (PHB) as one block and random
      copolymer of 3-hydroxyvalerate (3HV) and 3-hydroxyheptanoate (3HHp) as another
      block. The novel block polymer was studied by differential scanning calorimetry
      (DSC), nuclear magnetic resonance, and rheology measurements. DSC studies showed
      the polymer to possess two glass transition temperatures (T(g)), one melting
      temperature (T(m)) and one cool crystallization temperature (T(c)). Rheology
      studies clearly indicated a polymer chain re-arrangement in the copolymer; these
      studies confirmed the polymer to be a block copolymer, with over 70 mol%
      homopolymer (PHB) of 3-hydroxybutyrate (3HB) as one block and around 30 mol%
      random copolymers of 3HV and 3HHp as the second block. The block copolymer was
      shown to have the highest tensile strength and Young's modulus compared with a
      random copolymer with similar ratio and a blend of homopolymers PHB and PHVHHp
      with similar ratio. Compared with other commercially available PHA including PHB,
      PHBV, PHBHHx, and P3HB4HB, the short-chain- and medium-chain-length block
      copolymer PHB-b-PHVHHp showed differences in terms of mechanical properties and
      should draw more attentions from the PHA research community.

PMID- 21181146
TI  - Weedy lignocellulosic feedstock and microbial metabolic engineering: advancing
      the generation of 'Biofuel'.
AB  - Lignocellulosic materials are the most abundant renewable organic resources (~200
      billion tons annually) on earth that are readily available for conversion to
      ethanol and other value-added products, but they have not yet been tapped for the
      commercial production of fuel ethanol. The lignocellulosic substrates include
      woody substrates such as hardwood (birch and aspen, etc.) and softwood (spruce
      and pine, etc.), agro residues (wheat straw, sugarcane bagasse, corn stover,
      etc.), dedicated energy crops (switch grass, and Miscanthus etc.), weedy
      materials (Eicchornia crassipes, Lantana camara etc.), and municipal solid waste
      (food and kitchen waste, etc.). Despite the success achieved in the laboratory,
      there are limitations to success with lignocellulosic substrates on a commercial
      scale. The future of lignocellulosics is expected to lie in improvements of plant
      biomass, metabolic engineering of ethanol, and cellulolytic enzyme-producing
      microorganisms, fullest exploitation of weed materials, and process integration
      of the individual steps involved in bioethanol production. Issues related to the
      chemical composition of various weedy raw substrates for bioethanol formation,
      including chemical composition-based structural hydrolysis of the substrate, need
      special attention. This area could be opened up further by exploring genetically
      modified metabolic engineering routes in weedy materials and in biocatalysts that
      would make the production of bioethanol more efficient.

PMID- 21181147
TI  - Identification, cloning, heterologous expression, and characterization of a NADPH
      dependent 7beta-hydroxysteroid dehydrogenase from Collinsella aerofaciens.
AB  - A gene encoding an NADPH-dependent 7beta-hydroxysteroid dehydrogenase (7beta
      HSDH) from Collinsella aerofaciens DSM 3979 (ATCC 25986, formerly Eubacterium
      aerofaciens) was identified and cloned in this study. Sequence comparison of the
      translated amino acid sequence suggests that the enzyme belongs to the short
      chain dehydrogenase superfamily. This enzyme was expressed in Escherichia coli
      with a yield of 330 mg (5,828 U) per liter of culture. The enzyme catalyzes both
      the oxidation of ursodeoxycholic acid (UDA) forming 7-keto-lithocholic acid (KLA)
      and the reduction of KLA forming UDA acid in the presence of NADP(+) or NADPH,
      respectively. In the presence of NADPH, 7beta-HSDH can also reduce dehydrocholic
      acid. SDS-PAGE and gel filtration of the expressed and purified enzyme revealed a
      dimeric nature of 7beta-HSDH with a size of 30 kDa for each subunit. If used for
      the oxidation of UDA, its pH optimum is between 9 and 10 whereas for the
      reduction of KLA and dehydrocholic acid it shows an optimum between pH 4 to 6.
      Usage of the enzyme for the biotransformation of KLA in a 0.5-g scale showed that
      this 7beta-HSDH is a useful biocatalyst for producing UDA from suitable
      precursors in a preparative scale.

PMID- 21181148
TI  - Lactobacillus acidophilus as a live vehicle for oral immunization against chicken
      anemia virus.
AB  - The AcmA binding domains of Lactococcus lactis were used to display the VP1
      protein of chicken anemia virus (CAV) on Lactobacillus acidophilus. One and two
      repeats of the cell wall binding domain of acmA gene were amplified from L.
      lactis MG1363 genome and then inserted into co-expression vector, pBudCE4.1. The
      VP1 gene of CAV was then fused to the acmA sequences and the VP2 gene was cloned
      into the second MCS of the same vector before transformation into Escherichia
      coli. The expressed recombinant proteins were purified using a His-tag affinity
      column and mixed with a culture of L. acidophilus. Whole cell ELISA and
      immunofluorescence assay showed the binding of the recombinant VP1 protein on the
      surface of the bacterial cells. The lactobacilli cells carrying the CAV VP1
      protein were used to immunize specific pathogen-free chickens through the oral
      route. A moderate level of neutralizing antibody to CAV was detected in the serum
      of the immunized chickens. A VP1-specific proliferative response was observed in
      splenocytes of the chickens after oral immunization. The vaccinated groups also
      showed increased levels of Th1 cytokines interleukin (IL)-2, IL-12, and IFN
      gamma. These observations suggest that L. acidophilus can be used in the delivery
      of vaccines to chickens.

PMID- 21181149
TI  - Light requirements in microalgal photobioreactors: an overview of biophotonic
      aspects.
AB  - In order to enhance microalgal growth in photobioreactors (PBRs), light
      requirement is one of the most important parameters to be addressed; light should
      indeed be provided at the appropriate intensity, duration, and wavelength.
      Excessive intensity may lead to photo-oxidation and -inhibition, whereas low
      light levels will become growth-limiting. The constraint of light saturation may
      be overcome via either of two approaches: increasing photosynthetic efficiency by
      genetic engineering, aimed at changing the chlorophyll antenna size; or
      increasing flux tolerance, via tailoring the photonic spectrum, coupled with its
      intensity and temporal characteristics. These approaches will allow an increased
      control over the illumination features, leading to maximization of microalgal
      biomass and metabolite productivity. This minireview briefly introduces the
      nature of light, and describes its harvesting and transformation by microalgae,
      as well as its metabolic effects under excessively low or high supply.
      Optimization of the photosynthetic efficiency is discussed under the two
      approaches referred to above; the selection of light sources, coupled with recent
      improvements in light handling by PBRs, are chronologically reviewed and
      critically compared.

PMID- 21181150
TI  - Fermentation and microencapsulation of the nematophagous fungus Hirsutella
      rhossiliensis in a novel type of hollow beads.
AB  - In this work, fermentation and formulation aspects of the nematophagous fungus
      Hirsutella rhossiliensis BBA were investigated. When incubated in 2% (w/w)
      glucose and 0.5% (w/w) yeast extract medium in a 1-L Erlenmeyer flask without
      baffles, heavy pellet formation was observed. Only 40% of the mycelium had a size
      less than 500 MUm. When a flask with three baffles was used, the portion of
      mycelium <500 MUm rose to 95%. In the next step, the influence of aeration rate
      and stirrer speed on production of finely dispersed mycelium in a stirred tank
      reactor was investigated. The best fermentation results were obtained at 0.4 vvm
      and 400 rpm stirrer speed with 90% mycelium <500 MUm and 5 g/L biomass. Then,
      mycelium was microencapsulated in hollow beads based on sulfoethylcellulose
      (SEC). Experiments on the capsule nutrient reservoir showed that 15% (w/w) corn
      gluten and 0.5% (w/w) yeast extract could be replaced with 3% (w/w) autoclaved
      baker's yeast which was never used as capsule additive before. Radial growth of
      mycelium out of dried hollow beads containing 1% (w/w) biomass and 3% (w/w)
      baker's yeast was faster than for alginate beads containing equivalent amounts of
      biomass and yeast indicating a higher bio-control potential.

PMID- 21181151
TI  - C-terminal processing of tyrosinase is responsible for activation of Pholiota
      microspora proenzyme.
AB  - Tyrosinase is expressed as a 67-kDa protein in Pholiota microspora (synonym
      Pholiota nameko), whereas the same enzyme purified from fruiting bodies of P.
      microspora is a 42-kDa protein that is cleaved with a C-terminal 25-kDa
      polypeptide from the 67-kDa protein. To confirm the role of C-terminal processing
      in enzyme activity, we expressed a recombinant 67-kDa tyrosinase in Escherichia
      coli cells. To obtain a soluble protein, the recombinant tyrosinase was expressed
      as a thioredoxin fusion protein with an enterokinase-cleavable site. Enterokinase
      digestion of the fusion protein produced a recombinant 67-kDa tyrosinase that did
      not have any catalytic activity. However, chymotrypsin digestion of the fusion
      protein produced a recombinant 44-kDa tyrosinase that was catalytically active
      and had a 25-kDa cleaved C-terminal. Kinetic parameters of the 44-kDa tyrosinase
      were similar to those of the 42-kDa tyrosinase purified from the fruiting bodies.
      These results suggest that tyrosinase is expressed in P. microspora as a latent
      67-kDa proenzyme and is converted to the mature active 42-kDa enzyme by
      proteolytic processing of the C-terminal.

PMID- 21181152
TI  - Ceramic honeycomb as support for covalent immobilization of laccase from Trametes
      versicolor and transformation of nuclear fast red.
AB  - The covalent immobilization of laccase on an inorganic ceramic support was
      investigated. The intention was to find a system of enzyme and reactor for a
      universal immobilization procedure. Laccase from Trametes versicolor as model
      enzyme was chosen. The special honeycomb structure of the monolith can be applied
      for intensive mixing of the reaction compounds. An appropriate reactor with
      ceramic material was constructed allowing different setup for enzyme
      immobilization and its application. To test the success of the immobilization,
      2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) was used. The immobilized
      laccase was found to be stable over a time period of over 3 months. As an example
      for possible application for treatment of wastewater containing dyes, the
      conversion of nuclear fast red as model substrate was tested.

PMID- 21181153
TI  - Growth and recombinant protein expression with Escherichia coli in different
      batch cultivation media.
AB  - Parallel operated milliliter-scale stirred tank bioreactors were applied for
      recombinant protein expression studies in simple batch experiments without pH
      titration. An enzymatic glucose release system (EnBase), a complex medium, and
      the frequently used LB and TB media were compared with regard to growth of
      Escherichia coli and recombinant protein expression (alcohol dehydrogenase (ADH)
      from Lactobacillus brevis and formate dehydrogenase (FDH) from Candida boidinii).
      Dissolved oxygen and pH were recorded online, optical densities were measured at
      line, and the activities of ADH and FDH were analyzed offline. Best growth was
      observed in a complex medium with maximum dry cell weight concentrations of 14 g
      L(-1). EnBase cultivations enabled final dry cell weight concentrations between 6
      and 8 g L(-1). The pH remained nearly constant in EnBase cultivations due to the
      continuous glucose release, showing the usefulness of this glucose release system
      especially for pH-sensitive bioprocesses. Cell-specific enzyme activities varied
      considerably depending on the different media used. Maximum specific ADH
      activities were measured with the complex medium, 6 h after induction with IPTG,
      whereas the highest specific FDH activities were achieved with the EnBase medium
      at low glucose release profiles 24 h after induction. Hence, depending on the
      recombinant protein, different medium compositions, times for induction, and
      times for cell harvest have to be evaluated to achieve efficient expression of
      recombinant proteins in E. coli. A rapid experimental evaluation can easily be
      performed with parallel batch operated small-scale stirred tank bioreactors.

PMID- 21181154
TI  - Functional characterization of a gene cluster involved in gentisate catabolism in
      Rhodococcus sp. strain NCIMB 12038.
AB  - Rhodococcus sp. strain NCIMB 12038 utilizes naphthalene as a sole source of
      carbon and energy, and degrades naphthalene via salicylate and gentisate. To
      identify the genes involved in this pathway, we cloned and sequenced a 12-kb DNA
      fragment containing a gentisate catabolic gene cluster. Among the 13 complete
      open reading frames deduced from this fragment, three (narIKL) have been shown to
      encode the enzymes involved in the reactions of gentisate catabolism. NarI is
      gentisate 1,2-dioxygenase which converts gentisate to maleylpyruvate, NarL is a
      mycothiol-dependent maleylpyruvate isomerase which catalyzes the isomerization of
      maleylpyruvate to fumarylpyruvate, and NarK is a fumarylpyruvate hydrolase which
      hydrolyzes fumarylpyruvate to fumarate and pyruvate. The narX gene, which is
      divergently transcribed with narIKL, has been shown to encode a functional 3
      hydroxybenzoate 6-monooxygenase. This led us to discover that this strain is also
      capable of utilizing 3-hydroxybenzoate as its sole source of carbon and energy.
      Both NarL and NarX were purified to homogeneity as His-tagged proteins, and they
      were determined by gel filtration to exist as a trimer and a monomer,
      respectively. Our study suggested that the gentisate degradation pathway was
      shared by both naphthalene and 3-hydroxybenzoate catabolism in this strain.

PMID- 21181155
TI  - Structure and dynamics of nitrifier populations in a full-scale submerged
      membrane bioreactor during start-up.
AB  - Changes of microbial characteristics in a full-scale submerged membrane
      bioreactor system (capacity, 60,000 m(3) day(-1)) treating sewage were monitored
      over the start-up period (96 days). Fluorescence in situ hybridization analysis
      showed that the percentages of ammonia-oxidizing bacteria (AOB) and nitrite
      oxidizing bacteria (nitrobacter-related population) in total bacteria counted
      with DAPI staining increased significantly from 1.9% and 0.9% to 4.5% and 2.8%,
      corresponding to an increase of the specific ammonium oxidizing rate (from 0.06
      to 0.12 kg N kg(-1) mixed liquor suspended solids (MLSS) per day) and the
      specific nitrate forming rate (from 0.05 to 0.10 kg N kg(-1) MLSS day(-1)). Both
      the denaturing gradient gel electrophoresis of polymerase chain reaction and
      clone library results showed that the AOB was dominated by the genus
      Nitrosomonas, the diversity of which increased markedly with operational time.
      Most of the day 2 clones were closely related with the uncultured Nitrosomonas
      sp. clone Ninesprings-49S amoA gene (AY356450.1) originated from activated
      sludge, while the day 96 clone library showed a more diverse distribution
      characterized by the appearance of the oligotrophic nitrifiers like the
      Nitrosomonas oligotropha- and Nitrosomonas ureae-like bacteria, perhaps due to
      the interception by membrane and the low food-to-microorganisms ratio
      environment. The above results show that the membrane bioreactor system was
      characterized by the increased diversity and percentage of nitrifiers, which made
      it possible to achieve a stable and high efficient nitrification. Ammonia
      oxidizing archaea with the changing population structures were also detected, but
      their roles for ammonia oxidation in the system need further studies.

PMID- 21181156
TI  - Identification of a GH62 alpha-L-arabinofuranosidase specific for arabinoxylan
      produced by Penicillium chrysogenum.
AB  - An arabinoxylan arabinofuranohydrolase (AXS5) was purified from the culture
      filtrate of Penicillium chrysogenum 31B. A cDNA encoding AXS5 (axs5) was isolated
      by in vitro cloning using the N-terminal amino acid sequence of the native enzyme
      as a starting point. The deduced amino acid sequence of the axs5 gene has high
      similarities with those of arabinoxylan arabinofuranohydrolases of Aspergillus
      niger, Aspergillus tubingensis, and Aspergillus sojae. Module sequence analysis
      revealed that a "Glyco_hydro_62" was present at position 28-299 of AXS5. This is
      a family of alpha-L-arabinofuranosidases which are all members of glycoside
      hydrolase family 62. Recombinant AXS5 (rAXS5) expressed in Escherichia coli was
      highly active on arabinoxylan but not on branched sugar beet arabinan. (1)H-NMR
      analysis revealed that the rAXS5 cleaved arabinosyl side-chains linked to C-2 and
      C-3 of single-substituted xylose residues in arabinoxylan. Semi-quantitative RT
      PCR analysis indicated that expression of the axs5 gene in P. chrysogenum 31B was
      strongly induced by adding D-xylose and arabinoxylan to the culture medium.
      Moreover, two binding sites of XlnR, a transcriptional activator that regulates
      the expression of the genes encoding xylanolytic enzymes, are present in the
      upstream region of the axs5 gene. These results suggest that AXS5 is involved in
      xylan degradation.

PMID- 21181157
TI  - Intrabiliary rupture of hepatic hydatid cyst: multidetector-row CT demonstration.
AB  - Rupture of a hydatid cyst into the biliary tract, also known as cystobiliary
      communication, is the most common complication of hepatic hydatid cyst. This may
      lead to obstructive jaundice, pancreatitis, cholangitis, and sepsis with high
      mortality. Imaging plays an important role in the preoperative diagnosis of this
      condition which facilitates its management. We studied six patients with rupture
      of hepatic hydatid cyst into a large bile duct in whom multidetector-row CT
      (MDCT) suggested the diagnosis. The imaging findings included a single hepatic
      cyst less than 10 cm in diameter in all the cases; interruption of the cyst wall
      adjacent to a bile duct signifying cyst-bile duct communication was seen in five
      patients. The common bile duct was dilated in all the patients, with linear
      membranes in four and diffuse irregular high dense intrabiliary material observed
      within the common bile duct in two of them. Intrahepatic ducts were dilated in
      all the six cases and two patients showed linear dense contents within distended
      gallbladder. Subcapsular and intrathoracic rupture was associated in one patient
      each. MDCT demonstration of hydatid cyst in the liver together with a dilated
      common bile duct and distended gallbladder containing high density hydatid
      material suggest rupture of the cyst into biliary tree. MDCT enhances
      demonstration of the dilated common bile duct with hydatid material inside. The
      diagnosis is reinforced by the demonstration of the cystobiliary communication
      itself.

PMID- 21181159
TI  - Disparities in injury mortality between Uganda and the United States: comparative
      analysis of a neglected disease.
AB  - BACKGROUND: The burden of global injury-related deaths predominantly affects
      developing countries, which have little infrastructure to evaluate these
      disparities. We describe injury-related mortality patterns in Kampala, Uganda and
      compare them with data from the United States and San Francisco (SF), California.
      METHODS: We created a database in Kampala of deaths recorded by the City
      Mortuary, the Mulago Hospital Mortuary, and the Uganda Ministry of Health from
      July to December 2007. We analyzed the rate and odds ratios and compared them to
      data from the U.S. Centers for Disease Control and Prevention and the California
      Department of Public Health. RESULTS: In Kampala, 25% of all deaths were due to
      injuries (812/3303) versus 6% in SF and 7% in the United States. The odds of
      dying of injury in Kampala were 5.0 times higher than in SF and 4.2 times higher
      than in the United States. Age-standardized death rates indicate a 93% greater
      risk of dying from injury in Kampala than in SF. The mean age was lower in
      Kampala than in SF (29 vs. 44 years). The adult injury death rate (rate ratio, or
      RR) was higher in Kampala than in SF (2.3) or the United States (1.5). Head/neck
      injury was reported in 65% of injury deaths in Kampala compared to 34% in SF
      [odds ratio (OR) 3.7] and 28% in the US (OR 4.8). CONCLUSIONS: Urban injury
      related mortality is significantly higher in Uganda than in the United States.
      Injury preferentially affects adults in the prime of their economically
      productive years. These findings serve as a call for stronger injury prevention
      and control policies in Uganda.

PMID- 21181158
TI  - Mechanisms of T-cell protection from death by IRX-2: a new immunotherapeutic.
AB  - OBJECTIVES: IRX-2 is a novel immunotherapeutic containing physiologic quantities
      of several cytokines which protects human T lymphocytes from tumor-induced or
      drug-induced apoptosis. Here, we investigate the mechanisms responsible for IRX-2
      mediated protection of T lymphocytes exposed to tumor-derived microvesicles
      (TMV). METHODS: Jurkat cells or primary human T cells +/- IRX-2 were co-incubated
      with TMV and then examined by flow cytometry or Western blots for expression of
      molecules regulating cell survival (FLIP, Bcl-2, Bcl-xL, Mcl-1) or death (Fas,
      caspase 8, caspase 9, Bax, Bid). ANX V binding, caspase activation or cytochrome
      c release were also measured +/- cycloheximide (CHX) or +/- the Akt-specific
      inhibitor. Jurkat cells transfected with the cFLIP gene were used to evaluate the
      role of cFLIP in IRX-2-mediated protection. Effects of CHX on IRX-2-mediated
      protection and activation of NF-kappaB upon the TMV/IRX-2 treatment were also
      measured. RESULTS: IRX-2 protected T cells from apoptosis by preventing Fas
      overexpression induced by TMV and blocking caspase 8 activation by up-regulating
      cFLIP. Jurkat cells overexpressing cFLIP were more resistant to TMV-induced
      apoptosis than the mock-transfected cells (p < 0.02). Signaling via the PI3K/Akt
      pathway, IRX-2 corrected the imbalance of pro- versus anti-apoptotic proteins
      induced by TMV and promoted NF-kappaB translocation to the nucleus. CHX abolished
      IRX-2-mediated protection in T cells, suggesting that IRX-2 induces de novo
      synthesis of one or more proteins that are required for protection. CONCLUSIONS:
      This biologic may be therapeutically useful for protection of activated T cells
      from tumor-induced immune suppression and death.

PMID- 21181160
TI  - Anatomical changes due to pneumoperitoneum analyzed by MRI: an experimental study
      in pigs.
AB  - PURPOSE: Different effects on cardiovascular and respiratory systems and liver
      are associated with pneumoperitoneum. This study aimed to determine the
      morphological changes in the abdominal anatomy as a result of increased intra
      abdominal pressure due to pneumoperitoneum using MRI. METHODS: Ten healthy female
      pigs were used in this study. MRI studies of the abdomen in supine position were
      made before the creation of pneumoperitoneum and 1 h after increasing the
      pressure to 14 mmHg. Changes in area, volume, and longitudinal and transverse
      length of the liver were measured. The diameters of the lumen of the abdominal
      aorta, the inferior vena cava and portal vein were observed in three positions
      along the abdominal cavity. The position of the diaphragm after the induction of
      pneumoperitoneum was also analyzed. RESULTS: After induction of pneumoperitoneum,
      volume and transverse length of the liver was significantly increased, while peak
      area was decreased. Stenosis in the aortic lumen was observed (P < 0.05).
      Longitudinal and transverse diameters of the portal lumen were reduced, but
      significant differences were only found in the longitudinal diameter. Alterations
      in the diameter of the inferior vena cava lumen were obtained in three analyzed
      positions, but differences were significant only in two of them. A mean cranial
      displacement of the diaphragm equal to 25 mm was also observed. CONCLUSION:
      Increasing abdominal pressure up to laparoscopic pressure (14 mmHg) provokes
      morphological changes in the liver, vascular structures and diaphragm. These
      changes could be related to functional alterations that different organs
      experience after the induction of pneumoperitoneum.

PMID- 21181161
TI  - Additional erythrocytic and reticulocytic parameters helpful for diagnosis of
      hereditary spherocytosis: results of a multicentre study.
AB  - Hereditary spherocytosis (HS) is characterised by weakened vertical linkages
      between the membrane skeleton and the red blood cell's lipid bilayer, leading to
      the release of microparticles. All the reference tests suffer from specific
      limitations. The aim of this study was to develop easy to use diagnostic tool for
      screening of hereditary spherocytosis based on routinely acquired haematological
      parameters like percentage of microcytes, percentage of hypochromic cells,
      reticulocyte counts, and percentage of immature reticulocytes. The levels of
      haemoglobin, mean cell volume, mean corpuscular haemoglobin concentration,
      reticulocytes (Ret), immature reticulocytes fraction (IRF), hypochromic
      erythrocytes (Hypo-He) and microcytic erythrocytes (MicroR) were determined on
      EDTA samples on Sysmex instruments from a cohort of 45 confirmed SH. The HS group
      was then compared with haemolytical disorders, microcytic anaemia, healthy
      individuals and routine samples (n = 1,488). HS is characterised by a high Ret
      count without an equally elevated IRF. All 45 HS have Ret >80,000/MUl and
      Ret(10(9)/L)/IRF (%) greater than 7.7 (rule 1). Trait and mild HS had a Ret/IRF
      ratio greater than 19. Moderate and severe HS had increased MicroR and
      MicroR/Hypo-He (rule 2). Combination of both rules gave predictive positive value
      and negative predictive value of respectively 75% and 100% (n=1,488), which is
      much greater than single parameters or existing rules. This simple and fast
      diagnostic method could be used as an excellent screening tool for HS. It is also
      valid for mild HS, neonates and ABO incompatibilities and overcomes the lack of
      sensitivity of electrophoresis in ankyrin deficiencies.

PMID- 21181162
TI  - Pegylated liposomal doxorubicin in combination with dexamethasone and bortezomib
      (VMD) or lenalidomide (RMD) in multiple myeloma pretreated patients.

PMID- 21181163
TI  - Limited role of interim PET/CT in patients with diffuse large B-cell lymphoma
      treated with R-CHOP.
AB  - Positron emission tomography (PET) has been found useful in monitoring response
      to treatment of malignant lymphoma. We investigated the ability of interim PET to
      monitor response to standard dose R-CHOP chemotherapy in chemotherapy-naive
      patients with diffuse large B-cell lymphoma (DLBCL). Between March 2004 and April
      2009, 155 DLBCL patients treated with R-CHOP and available for interim and post
      treatment PET/CT were identified and included in this analysis. Response,
      progression-free survival (PFS), and overall survival (OS) were compared between
      interim PET/CT-negative and positive group, and among three patient groups which
      were categorized based on their interim and post-treatment PET/CT: those with
      early metabolic complete response (mCR), delayed mCR, and never mCR. Interim
      PET/CT-negative patients (n=100) showed superior CR rates to interim PET/CT
      positive patients (n=55; 93% vs 62%, P<0.001). However, there was no difference
      in PFS (P=0.07) and OS (P=0.24) between interim PET/CT-negative and positive
      group. We categorized patients into three groups, with 100 (64%) in the early mCR
      group, 35 (23%) in the delayed mCR group, and 20 (13%) in the never mCR group.
      Early mCR and delayed mCR group did not differ significantly in PFS (P=0.84) or
      OS (P=0.20). However, the survival outcome in the never mCR group was
      significantly inferior to the combined early and delayed mCR group. The result
      from this study suggests that interim PET/CT might be an inappropriate tool for
      designing risk-adaptive therapy in chemotherapy-naive DLBCL patients treated with
      R-CHOP. Prospective trials should be performed to clearly determine the role of
      interim PET/CT.

PMID- 21181164
TI  - Primary bone marrow diffuse large B cell lymphoma: a case series and review.
AB  - Diffuse large cell lymphoma involving bone marrow is not uncommon, but primary,
      de novo, bone marrow diffuse large B cell lymphoma (DLBCL) is rare. To understand
      the clinical features and outcomes of this distinct entity, we collected 12 cases
      in 5 years from a single-center database. They accounted for 1.16% of lymphoma,
      or 2.65% of diffuse large B cell lymphoma. Nine cases presented with fever of
      unknown origin. Lactate dehydrogenase levels were elevated in all but one case.
      Nine cases belonged to the high-risk group according to their international
      prognosis indexes (score 4 or 5). Four patients received no chemotherapy, all of
      whom died within 1 month. Four patients received cyclophosphamide, adriamycin,
      vincristine, and prednisolone (CHOP)-like chemotherapy, and their median survival
      was 13 months. Finally, four patients received rituximab 375 mg/m(2) in addition
      to CHOP-like chemotherapy. All of them had complete remission and three are still
      alive without relapse. We concluded that primary bone marrow DLBCL is a rare but
      distinctive subtype of lymphoma. The prognosis for this entity is poor but
      rituximab-based treatment is promising for improving its outcomes.

PMID- 21181165
TI  - [Sarcomas: classification with morphologic and genetic criteria].

PMID- 21181166
TI  - Proinflammatory cytokines, IL-1beta and TNF-alpha, induce expression of
      interleukin-34 mRNA via JNK- and p44/42 MAPK-NF-kappaB pathway but not p38
      pathway in osteoblasts.
AB  - The aim of this study is to investigate the induction of interleukin-34 (IL-34)
      and macrophage colony-stimulating factor (M-CSF) mRNA by inflammatory cytokines
      and the involvement of mitogen-activated protein kinases (MAPKs) in this
      signaling pathway in human osteoblasts as both IL-34 and M-CSF bind to the same
      receptor c-FMS. Among four inflammatory cytokines [(IL-1beta, IL-6, IL-17, and
      tumor necrosis factor-alpha (TNF-alpha)], IL-34 mRNA expression level was
      dramatically induced by IL-1beta (17-fold) and TNF-alpha (74-fold). IL-1beta and
      TNF-alpha activated the intracellular mitogen-activated protein kinases (MAPKs):
      p44/42 MAPK, p38, and c-Jun N-terminal kinase (JNK) as well as nuclear factor
      kappaB (NF-kappaB) in osteoblasts. IL-1beta- and TNF-alpha-mediated induction of
      IL-34 mRNA expression was decreased by JNK inhibitor. Interestingly, although
      treatment of MEK-1/2 inhibitor showed no reduction in the increase of IL-34 mRNA
      expression by cytokines, combination of MEK-1/2 inhibitor and JNK inhibitor
      significantly inhibited IL-1beta- and TNF-alpha-mediated IL-34 mRNA expression
      level compared to those by each inhibitor alone. On the other hand, M-CSF mRNA
      expression level was significantly induced by both IL-1beta and TNF-alpha by up
      to 7- and 11-fold, respectively. IL-1beta- and TNF-alpha-mediated induction of M
      CSF mRNA was not affected by p38, JNK, and MEK-1/2 inhibitors. However, NF-kappaB
      inhibitor completely inhibited the elevation of M-CSF mRNA expression by these
      cytokines. These results showed that proinflammatory cytokines, IL-1beta and TNF
      alpha, induced the expression of IL-34 mRNA via JNK and p44/42 MAPK but not p38
      in human osteoblasts while p38, JNK, and p44/42 MAPK were not involved in the
      induction of M-CSF mRNA expression by these cytokines.

PMID- 21181167
TI  - [Basic principles, planning and implementation of non-commercial clinical
      trials].
AB  - The proof of a drug's efficacy in randomized controlled trials is fundamental to
      therapeutic concepts determined by evidence-based medicine. Clinical trials
      according to the German Medicinal Products Act are performed by the
      pharmaceutical industry as company-sponsored trials (CST) driven by commercial
      interests or by non-commercial facilities as investigator-initiated trials (IIT),
      typically implemented by University Hospitals. In areas with no commercial
      interest, IITs are the driving force that generate scientific progress leading to
      treatment optimization. Therefore, non-commercial or investigator-initiated
      clinical trials are indispensable for improving medical care. To ensure the
      safety of trial participants and the quality of the data obtained, clinical
      trials are controlled by many legal regulations and internationally accepted
      quality standards. Therefore implementation of a clinical trial requires profound
      knowledge, qualified personnel, appropriate infrastructure, and substantial
      financial resources. In IITs unlike CSTs this has to be accomplished by the
      University without the assistance of the pharmaceutical industry. Since teaching
      of skills needed to perform clinical trials is still largely neglected in medical
      school and during residency this review addresses the (in clinical trials)
      inexperienced physician and outlines the characterization of a clinical trial,
      the range and division of responsibilities and the performance of clinical trials
      according to the German Medicinal Products Act.

PMID- 21181168
TI  - [Monotherapy of exudative age-related macular degeneration with ranibizumab in
      patients at cardiovascular risk. Advantages of ranibizumab compared to a
      combination with pegaptanib].
AB  - BACKGROUND: Intravitreal ranibizumab (Lucentis(r)) and pegaptanib (Macugen(r))
      are effective treatment options for exudative age-related macular degeneration
      (AMD). There might be some differences regarding effectiveness (higher with
      ranibizumab) and safety issues (presumed to be higher with pegaptanib), which led
      to the question whether these advantages might be combined. To clarify this
      question the current study was performed. METHODS: All patients treated for
      exudative AMD between February 2007 and May 2010 were evaluated for a potential
      cardiovascular risk profile. Patients with a positive history of coronary heart
      disease, proven by medical treatment, history of myocardial infarction, stent
      implantation or bypass operation or a history of stroke were classified as risk
      patients, while others without such a history were classified as non-risk
      patients. Risk patients were treated with a combination therapy (first injection:
      ranibizumab, second and third injections pegaptanib--combination group) when
      presenting between February 2008 and September 2009 or standard care (first,
      second and third injections ranibizumab--standard group) during upload. All
      patients were evaluated for best-corrected visual acuity on the day of diagnosis,
      injections during the upload phase and first follow-up visit after upload.
      RESULTS: Both groups did no differ regarding age, gender, subtype of choroidal
      neovascularization or waiting time between first visit and first injection.
      Visual acuity changes showed no differences up to the third injection and control
      visit. Visual acuity continued to improve within the standard group but rapidly
      declined in the combination group. CONCLUSIONS: Even patients at risk for
      cardiovascular accidents should not be treated with a combination therapy of
      ranibizumab and pegaptanib as this combination results in a decline of visual
      acuity during upload.

PMID- 21181170
TI  - Impaired carotid artery elastic function in patients with tetralogy of Fallot.
AB  - Complex congenital heart diseases with abnormal formation of the aorticopulmonary
      septum are also associated with defective large artery elastogenesis. In the
      current study, we tested the hypothesis that carotid artery elastic function was
      impaired in patients with tetralogy of Fallot (ToF). The study included 45 Fallot
      patients (male:female 27:18; age 21.0 +/- 11.8 years) and 45 age- and gender
      matched healthy control individuals. Carotid artery diameter, pulsatile
      distension, and intima-media thickness (IMT) were measured by echotracking
      device, and carotid blood pressure was determined using applanation tonometry.
      Carotid artery elasticity was characterized by compliance and distensibility
      coefficients, stiffness index beta, and incremental elastic modulus. All carotid
      artery elastic parameters showed significant differences between groups. The
      compliance coefficient was 36%, and the distensibility coefficient was 33%
      smaller, whereas stiffness index beta was 46% and incremental elastic modulus was
      40% larger in Fallot-patients. Fallot-patients also had larger carotid artery IMT
      as compared to that of healthy individuals. Carotid artery is markedly stiffer in
      Fallot-patients suggesting that impaired elastogenesis is a component of the
      congenital abnormality. Increased large artery stiffness might contribute
      directly and indirectly (through impairment of baroreflex function) to the higher
      mortality found in ToF patients.

PMID- 21181169
TI  - [Anti-TNF-alpha treatment for uveitis. Analysis of the current situation].
AB  - Biologicals are selectively acting proteins that demonstrated high efficacy in
      the treatment of chronic disorders. In particular, biologicals blocking tumor
      necrosis factor alpha (TNF-alpha), an essential cytokine in chronic inflammatory
      diseases, have demonstrated great promise. Experimental and clinical data
      indicate that TNF-alpha plays an important role in intraocular inflammation.
      Neutralization of TNF-alpha might therefore be a promising strategy for
      prevention and treatment of uveitis. Here we review the principle effects,
      therapeutic value, and potential side effects of anti-TNF agents in uveitis.

PMID- 21181171
TI  - Effect of intravascular ultrasound-guided adjuvant high-pressure non-compliant
      balloon post-dilation after drug-eluting stent implantation.
AB  - Drug-eluting stent (DES) expansion characteristics after aggressive high-pressure
      post-dilation using a non-compliant (NC) balloon have not been fully
      investigated. We evaluated 58 patients with native coronary lesions treated with
      DESs [24 paclitaxel eluting stents (PES) and 34 sirolimus-eluting stents (SES)].
      After post-dilation (12-14 atm) using a stent-mounted semi-compliant balloon to
      reduce stent edge injury, adjuvant high-pressure post-dilation using NC balloon
      was performed within the stents. Stent size, stent length, and NC balloon size
      were selected based on preinterventional intravascular ultrasound (IVUS)
      assessment. Stent underexpansion was defined according to criteria of the
      Multicenter Ultrasound Stenting in Coronaries (MUSIC) study as a minimal stent
      cross-sectional area <90% of the average reference lumen area. Resultant endpoint
      was to obtain optimal stent expansion. Serial changes of stent expansion and
      stent symmetry were calculated in each group. After stent-mounted semi-compliant
      balloon post-dilation, both stents could not achieve adequate percent stent
      expansion (PES 73 +/- 18% vs. SES 67 +/- 9%, p = 0.38). After high-pressure post
      dilation using an NC balloon, percent stent expansion was 97 +/- 14% in PES and
      91 +/- 13% in SES, respectively (p = 0.25). Axial stent symmetry indices also
      significantly improved in both groups. Although radial stent symmetry indices
      improved significantly in PES group, those in the SES group had no significant
      changes. Finally, frequency of stent underexpansion significantly reduced, 87-20%
      in PES and 92-15% in SES, respectively (p = 0.01) without any significant stent
      edge injury. DES expansion improved safely after adjuvant high-pressure post
      dilation using an NC balloon under IVUS guidance.

PMID- 21181172
TI  - Simultaneous and spontaneous multivessel coronary artery dissection presenting as
      congestive heart failure.
AB  - Spontaneous coronary artery dissection (SCAD) is a rare cause of myocardial
      ischemia. Multivessel SCAD is much rarer than single vessel involvement and acute
      coronary syndrome is the most frequent clinical presentation of a patient with
      SCAD. The patient in this report had SCAD in both the left anterior descending
      and right coronary arteries at the same time. However, the clinical manifestation
      was not acute coronary syndrome but rather congestive heart failure. Successful
      angioplasty and stent placement was performed and the symptoms of congestive
      heart failure were successfully resolved with medical treatment.

PMID- 21181173
TI  - Measurement of platelet reactivity of patients with cardiovascular disease on
      treatment with acetyl salicylic acid: a prospective study.
AB  - Acetyl salicylic acid (ASA) and clopidogrel are extensively used in the
      prevention of cardiovascular disease. However, the responsiveness to ASA
      treatment may vary among individuals. This study was conducted to investigate the
      profile and prevalence of ASA resistance in cardiac patients. From August 2007 to
      August 2008, a total of 282 cardiac patients were enrolled. Two study groups were
      identified: patients taking 100 mg ASA daily but without clopidogrel, and
      patients taking both 100 mg ASA and 75 mg clopidogrel daily. Platelet function
      was determined with the Multiplate analyzer to determine platelet responsiveness.
      Salicylate blood level was measured for all patients on ASA. Seventy-three
      patients (26%) were determined to be nonresponsive to ASA, and 45 patients (16%)
      were partially responsive, whereas 164 patients (58.2%) were responsive to ASA.
      Myocardial infarction and coronary obstruction were both strongly associated with
      ASA nonresponsiveness (p < 0.001). ASA resistance occurred more in female
      patients (p = 0.002). The salicylate blood level was found to be low in ASA
      resistant patients (35.33 +/- 50.22 mg/l) and higher in sensitive patients (54.26
      +/- 18.7 mg/l; p < 0.001). Quantitative assessment of platelet functions is
      predictive of ASA treatment failure in individual patients. Dual antiplatelet
      treatment with clopidogrel and ASA was found to have greater inhibitory effects
      on platelet aggregation than either agent alone. Non-adherence may be a
      significant mediator of poor outcome.

PMID- 21181174
TI  - Absence of left ventricular concentric hypertrophy: a prerequisite for zero
      coronary calcium score.
AB  - The identification and intervention of factors associated with a coronary artery
      calcification (CAC) score of zero, suggesting the absence of significant coronary
      artery disease (CAD) with high probability, would be meaningful in the clinical
      setting. Thus far, the relationship between CAC and left ventricular (LV)
      hypertrophy has not been documented. We identified factors associated with a CAC
      score of zero and evaluated the relationship between this score and LV concentric
      hypertrophy in 309 consecutive patients with suspected CAD who were clinically
      indicated to undergo multislice computed tomography angiography for coronary
      artery evaluation. The quantitative CAC score was calculated according to
      Agatston's method. The total coronary calcium score (TCS) was defined as the sum
      of the scores for each lesion. Four absolute TCS categories were considered:
      zero, mild (0-100), moderate (100-400), and severe (>400). LV hypertrophy was
      classified into concentric (LV mass index >104 g/m(2) in women or >116 g/m(2) in
      men; LV end-diastolic volume index <=109.2 mL/m(2)) and eccentric (LV end
      diastolic volume index >109.2 mL/m(2)) patterns. In the zero-TCS group, the
      frequency of LV concentric hypertrophy was extremely low (zero 6%, mild 17%,
      moderate 26%, severe 19%). Multivariate analysis revealed that age,
      hypercholesterolemia, diabetes mellitus, LV concentric hypertrophy, and LV mass
      index, but not hypertension, were the independent factors associated with a CAC
      score of zero. The present study demonstrated that the absence of LV concentric
      hypertrophy was a prerequisite for a CAC score of zero. That is, the presence of
      LV concentric hypertrophy, which indicated more severe underlying hypertension,
      long duration, or poor control of blood pressure, implicates the presence of CAC.

PMID- 21181175
TI  - Placement of Ommaya reservoir following endoscopic third ventriculostomy in
      pediatric hydrocephalic patients: a critical reappraisal.
AB  - PURPOSE: Endoscopic third ventriculostomy (ETV) has become standard for
      obstructive hydrocephalus. Even a successful ETV can obstruct, leading to
      recurrence of symptoms and even death. A possible solution to this problem is
      leaving an Ommaya reservoir (OR) following the ETV. OR can be tapped in an
      emergency and for diagnostic purposes. No specific complications have been
      attributed to OR in this setting. We present our experience with OR in children
      undergoing ETV for hydrocephalus. MATERIALS AND METHODS: A retrospective study
      was conducted in hydrocephalic children that underwent ETV with OR insertion over
      13 years (1997-2010) from a single institution. Data were collected from charts
      and follow-ups. RESULTS: Twelve patients (from 200 patients who had an ETV)
      underwent placement of OR with ETV. OR was reserved for a subgroup of patients in
      whom we anticipated complications-in children that presented with acute
      hydrocephalus and were in deteriorating condition, for pathologies believed to
      have a low predicted ETV success rate, or when the surgeon felt that the ETV
      procedure was suboptimal. OR was tapped in eight patients. Complications occurred
      in four patients: two cases of subdural effusion, one case of chronic subdural
      hematoma, and one CSF leak. Four ORs were removed due to complications, and four
      were converted to shunts. CONCLUSIONS: OR should be considered in selected
      patients undergoing ETV. Despite its obvious advantages, OR may be associated
      with a relatively high risk of extraaxial fluid collections. This association
      requires further investigation.

PMID- 21181176
TI  - Late-breaking clinical trials presented at the American Heart Association
      Congress in Chicago 2010.
AB  - This article gives an overview on the late-breaking clinical trials in the field
      of cardiovascular medicine which were presented during the hotline sessions at
      the American Heart Association Congress, held in Chicago, USA, from 13 to 17th
      November 2010. The data have been presented by leading experts in the field with
      relevant positions in the trials. The summaries provided in the manuscript were
      generated from the oral presentations and the webcasts of the American Heart
      Association (Laufs in Clin Res Cardiol 97:1-11, 2008; Mollmann in Clin Res
      Cardiol 98:1-7, 2009). The following papers are discussed in alphabetical order:
      ACT, ADVANCE, ASCEND-HF, ASCOT-CRP, CLOSURE I, DEFINE, EMPHASIS-HF, GRAVITAS, P
      OM3, RAFT, ROCKET-AF, SMART-AV, SYMPLICITY HTN-2, TELE-HF, TIM-HF.

PMID- 21181177
TI  - Exercise-induced modulation of cardiac lipid content in healthy lean young men.
AB  - Cardiac lipid accumulation is associated with decreased cardiac function and
      energy status (PCr/ATP). It has been suggested that elevated plasma fatty acid
      (FA) concentrations are responsible for the cardiac lipid accumulation.
      Therefore, the aim of the present study was to investigate if elevating plasma FA
      concentrations by exercise results in an increased cardiac lipid content, and if
      this influences cardiac function and energy status. Eleven male subjects (age
      25.4 +/- 1.1 years, BMI 23.6 +/- 0.8 kg/m2) performed a 2-h cycling protocol,
      once while staying fasted and once while ingesting glucose, to create a state of
      high versus low plasma FA concentrations, respectively. Cardiac lipid content was
      measured by proton magnetic resonance spectroscopy (1H-MRS) at baseline, directly
      after exercise and again 4 h post-exercise, together with systolic function (by
      multi-slice cine-MRI) and cardiac energy status (by 31P-MRS). Plasma FA
      concentrations were increased threefold during exercise and ninefold during
      recovery in the fasted state compared with the glucose-fed state (p < 0.01).
      Cardiac lipid content was elevated at the end of the fasted test day (from 0.26
      +/- 0.04 to 0.44 +/- 0.04%, p = 0.003), while it did not change with glucose
      supplementation (from 0.32 +/- 0.03 to 0.26 +/- 0.05%, p = 0.272). Furthermore,
      PCr/ATP was decreased by 32% in the high plasma FA state compared with the low FA
      state (n = 6, p = 0.014). However, in the high FA state, the ejection fraction 4
      h post-exercise was higher compared with the low FA state (63 +/- 2 vs. 59 +/-
      2%, p = 0.018). Elevated plasma FA concentrations, induced by exercise in the
      fasted state, lead to increased cardiac lipid content, but do not acutely hamper
      systolic function. Although the lower cardiac energy status is in line with a
      lipotoxic action of cardiac lipid content, a causal relationship cannot be
      proven.

PMID- 21181179
TI  - Effects of neck muscle vibration on subjective visual vertical: comparative
      analysis with effects on nystagmus.
AB  - In patients with unilateral vestibular dysfunction, vibratory stimulation to the
      neck muscles not only induces shift of the subjective visual vertical (SVV), but
      also enhances the generation of nystagmus. In the present study, the effects of
      neck vibration on the SVV were compared with those on nystagmus in patients with
      unilateral vestibular schwannoma (14 patients; 6 males and 8 females, mean age
      54.2 years). The results indicated that the presence of nystagmus and magnitude
      of the SVV were generally correlated, neck vibration significantly increased the
      abnormal shift of the SVV and the presence of nystagmus, and the effects of
      vibration to the ipsilateral dorsal neck were significantly larger than those to
      the contralateral dorsal neck on the SVV, whereas no significant difference was
      observed in slow phase velocity of nystagmus. The present study suggests that
      both SVV and nystagmus induced by vibration have many similar clinical features
      and may be important in assessing the unilateral vestibular dysfunction.

PMID- 21181178
TI  - The physiological impact of high altitude on nasal and lower airway parameters.
AB  - The aim of this study was to investigate the impact of high altitude on nasal and
      lower airway parameters in a healthy population. This was a prospective study of
      61 individuals who climbed to the summit of Mount Kackar, at 3,937 m. Peak nasal
      inspiratory flow rates were recorded in all participants at sea level and at the
      summit. In 32 participants who ascended to the summit, sea-level and summit peak
      expiratory flow rates and olfactory function were evaluated. A rise in altitude
      significantly decreased peak nasal inspiratory flow by a mean of 27.43%. Mean
      peak expiratory flow values measured at the summit were 8.94% lower than basal
      values. Between-value differences were statistically significant (p < 0.001, p <
      0.05). At high altitude, there was a significant decrease in olfactory function,
      as determined by a significant reduction in smell detection (p < 0.05) and smell
      identification (p < 0.05). The effect of high altitude on nasal function was
      found to parallel that of the effect on lower airway function, together
      accounting for an adverse effect on airway flow rates. The nasal mucosa responded
      to high altitude with an increase in airway resistance and a consequent impaired
      sense of smell.

PMID- 21181180
TI  - The importance of metric view for photodocumentation of facial reconstructive
      surgery: a single blinded survey.
AB  - Photodocumentation is an essential part of dermatooncology and reconstructive
      surgery. The purpose of this study is to suggest an imaging technique named
      metric view (photograph of the lesion with a surgical ruler) and to assess the
      accuracy of different views. Frontal, close-up and metric views were taken from
      the lesions of ten different cases. All the photographs were showed to 30 medical
      professionals and a prediction about the size of the lesion was requested
      individually. The relationship between the prediction values for three views and
      the exact size of the lesions were statistically analysed. The precise prediction
      of the exact size was only achieved in metric view of one case. In addition, the
      most approximate prediction values were obtained in metric views. The statistical
      analysis demonstrated that there was no statistically significant difference
      between the prediction values for metric view and exact size of the lesions in
      half of the cases. In contrast, statistically significant differences were
      detected in almost all of the prediction values for frontal and close-up views.
      Frontal and close-up views are not adequate to represent the size of the lesions.
      Metric view may enable a rational solution for a better representation.

PMID- 21181182
TI  - Recognition of Professor Thomas Brandt.

PMID- 21181181
TI  - Predictors of clinical and social outcomes following involuntary hospital
      admission: a prospective observational study.
AB  - The Study aimed to assess clinical and social outcomes following involuntary
      admissions over 1 year and identify socio-demographic and clinical patient
      characteristics associated with more or less favourable outcomes. Seven hundred
      and seventy-eight involuntary patients admitted to one of 22 hospitals in England
      were assessed within the first week after admission and at 1 month, 3 month and
      12 month follow-ups. Outcome criteria were symptom levels, global functioning,
      objective social outcomes, and subjective quality of life (SQOL). Baseline
      characteristics and patients' initial experience were tested as predictors.
      Symptom levels and global functioning improved moderately. Objective social
      outcomes showed a small, but statistically significant deterioration, and SQOL a
      small, but significant improvement at 1 year. In multivariable analyses,
      admission due to risk to oneself and receiving benefits predicted poorer symptom
      outcomes. Female gender and higher perceived coercion were associated with better
      objective social outcomes, whilst higher initial satisfaction with treatment
      predicted more positive SQOL at follow-ups. Over a 1-year period following
      involuntary hospital admission, patients on average showed only limited health
      and social gains. Different types of outcomes are associated with different
      predictor variables. Patients' initial experience of treatment, in the form of
      perceived coercion or satisfaction with treatment, has predictive value for up to
      a year following the admission.

PMID- 21181183
TI  - Thrombolytic therapy and visuoperceptual functions in right hemisphere infarct
      patients.
AB  - This study examines the association between thrombolysis and visuoperceptual
      functions in right hemisphere (RH) infarct patients. Fifty-six consecutive
      patients with first acute RH infarct were matched for age, years of education and
      stroke severity at the time of admission to the emergency department (baseline
      NIHSS; National Institute of Health Stroke Scale), compared according to whether
      (T+) or not (T-) they received thrombolysis. Neurological (NIHSS at hospital
      ward; Barthel index; BI) and neuropsychological examinations were conducted 4
      days after onset. Visuoconstructive abilities were assessed with the block design
      and visual search and reasoning with the picture completion subtests of the
      Wechsler Adult Intelligence Scale revised. Visual neglect was assessed with the
      conventional subtests of the Behavioural Inattention test and visual memory with
      the visual reproduction subtest of the Wechsler Memory Scale Revised. T+ and T-
      patients did not differ in baseline NIHSS, age, years of education, hemianopia,
      hemiparesis, or in basic ADL (BI). T- patients had more severe strokes (NIHSS at
      hospital ward) and poorer visuoconstructive abilities than T+ patients. Our
      results indicate that thrombolysis has a favourable effect on visuoperceptual
      functions in acute stroke.

PMID- 21181184
TI  - Validation of the caregivers' satisfaction with Stroke Care Questionnaire: C-SASC
      hospital scale.
AB  - To date, researchers have lacked a validated instrument to measure stroke
      caregivers' satisfaction with hospital care. We adjusted a validated patient
      version of satisfaction with hospital care for stroke caregivers and tested the
      11-item caregivers' satisfaction with hospital care (C-SASC hospital scale) on
      caregivers of stroke patients admitted to nine stroke service facilities in the
      Netherlands. Stroke patients were identified through the stroke service
      facilities; caregivers were identified through the patients. We collected
      admission demographic data from the caregivers and gave them the C-SASC hospital
      scale. We tested the instrument by means of structural equation modeling and
      examined its validity and reliability. After the elimination of three items, the
      confirmatory factor analyses revealed good indices of fit with the resulting
      eight-item C-SASC hospital scale. Cronbach's alpha was high (0.85) and
      correlations with general satisfaction items with hospital care ranged from 0.594
      to 0.594 (convergent validity). No significant relations were found with health
      and quality of life (divergent validity). Such results indicate strong construct
      validity. We conclude that the C-SASC hospital scale is a promising instrument
      for measuring stroke caregivers' satisfaction with hospital stroke care.

PMID- 21181186
TI  - Rhabdomyolysis/myoglobinemia and NSAID during 48 h ultra-endurance exercise
      (adventure racing).
AB  - Our purpose is to determine whether rhabdomyolysis with myoglobinemia exists
      during a 48+ h adventure race and if there is a correlation with NSAID use, race
      time and perceived pain or exertion. Blood samples for analyses of myoglobin (Mb)
      were collected, and perception of exertion and pain was registered on the Borg
      RPE and CR scales, from 20 subjects (3 female, 17 male) Pre-, Mid- and Post-race.
      Subjects were asked about NSAID use at each sampling and within 12 h pre-race.
      The result observed was a significant rise in Mb throughout the race, with the
      NSAID group (n = 6) having significantly lower Mb-Post than the no-NSAID group (n
      = 14). High Mb-Pre and Post correlated to shorter race time and high Mb-Pre to
      lower Pain-post. Race time also correlated to NSAID use, with the NSAID group
      having significantly longer race time than the no-NSAID group. Rhabdomyolysis
      with myoglobinemia, which might be reduced with NSAID use, exists during a 48+ h
      adventure race. Indications that high Mb-levels correlate with shorter race time
      and less pain, and the reasons for the NSAID groups longer race time, warrants
      further investigation.

PMID- 21181185
TI  - Magnetic resonance imaging in progressive supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is a tauopathy, presenting clinically most
      often with a symmetrical akinetic-rigid syndrome, postural instability,
      supranuclear gaze palsy and frontal dementia. In the absence of reliably
      validated biomarkers, the diagnosis of PSP in vivo is presently based on clinical
      criteria, which to date do not include supporting imaging findings, as is
      accepted for other neurodegenerative diseases. However, data from conventional
      magnetic resonance imaging (MRI) and various advanced MRI techniques including
      magnetic resonance volumetry, voxel-based morphometry, diffusion-weighted and
      diffusion-tensor imaging, magnetization transfer imaging and proton resonance
      spectroscopy suggest that MRI can contribute valuable information for the
      differential diagnosis of PSP. We review here the presently published literature
      concerning MRI in PSP and discuss the potential role of MRI in differentiating
      PSP from other parkinsonian syndromes.

PMID- 21181188
TI  - Evaluation of indigenous plant extracts against the malarial vector, Anopheles
      stephensi (Liston) (Diptera: Culicidae).
AB  - Since ancient times, plant and microbial products were used in various aspects.
      However, their use against insects decreased when chemical products became
      developed. Recently, concerns increased with respect to public health and
      environmental security requiring detection of natural products that may be used
      against insects. In this study, mosquito Larvicidal and ovicidal activity of
      crude hexane, ethyl acetate, benzene, chloroform, and methanol extracts of the
      leaf of three plants, Eclipta alba, Cardiospermum halicacabum, and Andrographis
      paniculata, were tested against the early third-instar larvae of Anopheles
      stephensi (Liston) (Diptera: Culicidae). The larval mortality was observed after
      24 h of exposure. All extracts showed moderate larvicidal effects; however, the
      highest larval mortality was found in methanol extract of A. paniculata, E. alba,
      and C. halicacabum against the larvae of A. stephensi (LC(50) = 79.68, 112.56,
      and 133.01 ppm; LC(90) = 154.66, 220.68, and 270.72 ppm), respectively. Mean
      percent hatchability of the ovicidal activity was observed 48 h post-treatment.
      The percent hatchability was inversely proportional to the concentration of
      extract and directly proportional to the eggs. Mortality of 100% with methanol
      and ethyl acetate extract of A. paniculata and methanol extract of E. alba were
      exerted at 200 ppm and methanol and benzene extract of C. halicacabum exerted at
      150 ppm. This is an ideal eco-friendly approach for the control of the malaria
      vector, A. stephensi. Therefore, this study provides first report on the
      larvicidal and ovicidal activities against malaria vector, A. stephensi of E.
      alba plant extracts.

PMID- 21181189
TI  - Comparison of faecal techniques including FLOTAC for copromicroscopic detection
      of first stage larvae of Angiostrongylus vasorum.
AB  - Angiostrongylus vasorum is a metastrongylid nematode that resides in the
      pulmonary arteries and the right heart chambers. In dogs, infection results in
      respiratory, bleeding and neurological disorders and further clinical signs. In
      the present study, FLOTAC was evaluated for the detection of first-stage larvae
      (L1) of A. vasorum in canine faecal samples. This technique is based on the
      counting of parasitic stages (eggs, larvae, oocysts and cysts) in chambers after
      spinning of faecal samples onto a surface. In a first step, nine flotation
      solutions were evaluated using faeces of two experimentally infected dogs. Zinc
      sulphate (specific gravity (s.g.) 1.2) and zinc sulphate plus potassium
      iodomercurate (s.g. 1.45) gave good results. However, with the latter technique,
      the larvae were slightly deformed. Subsequently, FLOTAC, using zinc sulphate, was
      compared through a randomisation technique with McMaster, flotation in tube and
      Baermann-Wetzel technique. The mean larvae per gramme (LPG) obtained by the
      FLOTAC for both dogs was significantly higher (P < 0.05) than those obtained by
      the other three techniques (the means of the other techniques all lie below the
      95% CI of the mean LPG of the FLOTAC technique). In addition, the FLOTAC results
      were consistent across replicates with only Poisson (or random) variation between
      individual replicates. The other techniques appear to be less consistent with
      evidence of extra-Poisson variation in at least one of the two dogs across the
      replicates within each technique. The FLOTAC technique may contribute to an
      improvement of the ability to diagnose canine lungworm infections and represent a
      valuable alternative for larval counting of A. vasorum in faecal samples,
      especially following transport or storage where there may be limited larvae
      viability, and larval migration techniques cannot be used.

PMID- 21181190
TI  - Spermatological characters of bothriocephalideans (Cestoda) inferred from an
      ultrastructural study on Oncodiscus sauridae and Senga sp.
AB  - Spermiogenesis and ultrastructure of the spermatozoon of two bothriocephalidean
      cestodes, Oncodiscus sauridae from the lizardfish Saurida nebulosa Valenciennes,
      1850 and Senga sp. from the eel Mastacembelus armatus (Lacepede, 1800), have been
      studied using transmission electron microscopy. Spermiogenesis included the
      formation of a zone of differentiation, where two centrioles associated with the
      striated rootlets occur. An intercentriolar body composed of one thick central
      electron-dense plate and two thinner plates on each side appears between two
      centrioles. Two flagella of unequal length grow and undergo a vertical rotation
      and proximodistal fusion with the median cytoplasmic process. Subsequently, the
      nucleus penetrates into the median cytoplasmic extension. The electron-dense
      material in the early stages of spermiogenesis is characteristic for the apical
      region of the differentiation zone. This electron-dense material is typical for
      basal tapeworms, e.g., Bothriocephalidea, Caryophyllidea, Diphyllobothriidea, and
      Spathebothriidea. The mature spermatozoon of O. sauridae and Senga sp. is
      filiform and possesses two axonemes of the 9 + "1" trepaxonematan pattern, a
      nucleus, cortical microtubules, and electron-dense granules. The anterior part of
      the gamete contains a single electron-dense crested body. The most interesting
      character found is the presence of a ring of cortical microtubules encircling the
      axoneme in the anterior part of the spermatozoon. This feature has been detected
      only for species of the order Bothriocephalidea and may represent a synapomorphy
      of these tapeworms. A classical pattern for spermatological characters
      (spermiogenesis of type I with dense material in early stages and sperm of type
      II with a characteristic ring of cortical microtubules in the anterior part) in
      Bothriocephalidea is discussed.

PMID- 21181191
TI  - Evidence of congenital transmission of Neospora caninum in naturally infected
      water buffalo (Bubalus bubalis) fetus from Brazil.
AB  - The aim of this study was to determine the congenital infection by Neospora
      caninum in the water buffalo (Bubalus bubalis), a natural intermediate host. Nine
      pregnant water buffalos, raised under free-grazing condition, were slaughtered,
      and their fetuses were collected. Samples of brain and thoracic fluid were
      obtained from those fetuses, with gestational ages ranging from 2 to 5 months.
      The DNA of N. caninum was detected and identified in the brain of one of those
      fetuses, using two PCR assays, one directed to the Nc5 gene and the other, to the
      common toxoplasmatiid ITS1 sequence. The DNA fragments produced on PCR were
      sequenced, and N. caninum was confirmed in the samples. No antibodies to N.
      caninum were detected on any sample of thoracic fluid by immunofluorescent
      antibody test (IFAT < 25). This is the first confirmation of congenital
      transmission of N. caninum in water buffalos.

PMID- 21181192
TI  - Evaluation of green synthesized silver nanoparticles against parasites.
AB  - Green nanoparticle synthesis has been achieved using environmentally acceptable
      plant extract and eco-friendly reducing and capping agents. The present study was
      based on assessments of the antiparasitic activities to determine the efficacies
      of synthesized silver nanoparticles (AgNPs) using aqueous leaf extract of Mimosa
      pudica Gaertn (Mimosaceae) against the larvae of malaria vector, Anopheles
      subpictus Grassi, filariasis vector Culex quinquefasciatus Say (Diptera:
      Culicidae), and Rhipicephalus (Boophilus) microplus Canestrini (Acari: Ixodidae).
      Parasite larvae were exposed to varying concentrations of aqueous extract of M.
      pudica and synthesized AgNPs for 24 h. AgNPs were rapidly synthesized using the
      leaf extract of M. pudica and the formation of nanoparticles was observed within
      6 h. The results recorded from UV-vis spectrum, Fourier transform infrared, X-ray
      diffraction, scanning electron microscopy, and transmission electron microscopy
      support the biosynthesis and characterization of AgNPs. The maximum efficacy was
      observed in synthesized AgNPs against the larvae of A. subpictus, C.
      quinquefasciatus, and R. microplus (LC(50) = 13.90, 11.73, and 8.98 mg/L, r (2) =
      0.411, 0.286, and 0.479), respectively. This is the first report on antiparasitic
      activity of the plant extract and synthesized AgNPs.

PMID- 21181193
TI  - Serodiagnosis of experimental sparganum infections of mice and human sparganosis
      by ELISA using ES antigens of Spirometra mansoni spargana.
AB  - We conducted a study of serodiagnosis of experimental sparganum infections of
      mice and human sparganosis by enzyme-linked immunosorbent assay (ELISA) using
      excretory-secretory (ES) antigens of Spirometra mansoni spargana and compared the
      sensitivity and specificity of crude and ES antigens for detecting the specific
      anti-sparganum IgG antibodies. By crude antigen ELISA and ES antigen ELISA, anti
      sparganum IgG was detected in all of 30 serum samples of the infected mice; no
      cross-reactions were observed in serum samples of the mice infected with
      Trichinella spiralis, Schistosoma japanicum, Toxoplasma gondii, and normal mice.
      Anti-sparganum IgG was detected by ES antigen ELISA in sera of mice infected with
      one, two, four, six, and eight spargana at 3 weeks post-infection (wpi), with a
      detection rate of 100%, and lasted to 18 wpi when the experiment was ended. The
      difference in anti-sparganum antibody levels among five groups of the infected
      mice was statistically significant (F=245.296, p<0.05); the antibody levels were
      correlated with infecting doses of spargana (r=0.323, p<0.05). The sensitivity of
      both ELISA in detecting the serum samples of patients with sparganosis was 100%
      (20/20), but 96.72% (59/61) of specificity of ES antigen ELISA in detecting serum
      samples of patients with cysticercosis, echinococcosis, paragonimiosis,
      clonorchiosis, and schistosomiasis, and healthy persons was significantly greater
      than 72.13% (44/61) of crude antigen ELISA (chi (2) = 14.027, p<0.05). Our
      finding indicates that ELISA using ES antigens of S. mansoni spargana may be
      applied to the specific early serodiagnosis of sparganosis.

PMID- 21181194
TI  - Changes in the activity and kinetics of mouse intestinal glutathione transferase
      during experimental trichinellosis.
AB  - The glutathione S-transferases (GSTs) are a group of multifunctional enzymes,
      which play a critical role in cellular detoxification. Our investigations deal
      with the contribution of GST in the biochemical defense against Trichinella
      spiralis infection. The aim of this study was to examine the effect of T.
      spiralis infection on the total activity and kinetic properties of cytosolic GST
      in the intestine during the intestinal phase of experimental trichinellosis in
      mice. Our results showed a statistically significant increase (relative to the
      uninfected control) in the total GST activity both in the small and large
      intestines of the infected mice. Moreover, we observed changes in the kinetics of
      substrate saturation of GST. Trichinellosis in the small intestine caused a 12
      fold decrease in the low K (m) value and a sixfold increase in the high K (m)
      value. In the large intestine, infection with T. spiralis caused only a fivefold
      increase in the low K (m) value, whereas the high K (m) value remained unchanged.
      We suggest that GST from the mouse small intestine could be involved in the
      detoxification of parasite excretory-secretory products released to the host
      intestine during trichinellosis and that these products influence the quaternary
      structure of this enzyme.

PMID- 21181195
TI  - First detection and genotyping of Encephalitozoon cuniculi in a new host species,
      gyrfalcon (Falco rusticolus).
AB  - Recently, the pathogenic species of microsporidia of the genus Encephalitozoon
      have been detected increasingly, also in representatives of the Aves class. Our
      study presents laboratory proof of Encephalitozoon cuniculi (E. cuniculi)
      genotype II in a new host, gyrfalcon (Falco rusticolus), with suspect
      microsporidiosis. E. cuniculi is an obligate intracellular microsporidian
      parasite that infects a wide range of mammalian hosts, including humans.
      Characterization of the internal transcribed spacer of the rRNA gene has
      identified three genotypes of E. cuniculi based on the number of 5'-GTTT-3'
      repeats present: a genotype I from rabbits and mice, containing three repeats; a
      genotype II from mice and dogs, containing two repeats; and a genotype III from
      dogs and fox, containing four repeats. Samples of faeces from 30 gyrfalcons were
      examined for the presence of microsporidia spores, using microscopical, molecular
      methods and sequencing. Microscopic analysis showed presence of brightly
      fluorescing oval shapes of size 1.5 * 3 MUm, characteristic of the strain
      Microsporidia in five samples. The PCR method, using species non-specific
      (530F/580R) and species-specific (ECUNR/ECUNF) primers, proved the presence of E.
      cuniculi spores in two samples. After sequencing were confirmed, E. cuniculi
      genotype II which implies new host species for this parasite.

PMID- 21181196
TI  - Characterization of ectoparasites in an urban cat (Felis catus Linnaeus, 1758)
      population of Rio de Janeiro, Brazil.
AB  - Ectoparasites are capable of transmitting infectious diseases and, therefore, are
      of zoonotic concern. Cats submitted to a spay/neuter program in the city of Rio
      de Janeiro were examined to determine the distribution of ectoparasites in cats
      from a city with a tropical climate. Independent of gender, breed, or age, 292
      cats were combed and subjected to otoscopic examination. Ectoparasites were
      collected, and blood samples were taken to determine packed cell volume. The
      majority of the 292 cats were female (71%), and most of them were categorized as
      domestic short hair cats (92%). Different species of ectoparasites that produced
      both single agent and multi-agent infestations were detected in these cats. Most
      cats were infested by Ctenocephalides felis (60%); however, other ectoparasites
      were found to a lesser degree in the sampled population (Felicola subrostratus
      (5.4%), Rhipicephalus sanguineus (1.4%), Lynxacarus radovskyi (1%), and Otodectes
      cynotis (6.2%)). Within the infested cats, 16.3% were also anemic, and there was
      a significant association between the occurrence of anemia and flea infestation.
      Of all sampled cats, 65% were infested by at least one species of ectoparasites,
      which suggests both a heavy infestation of the environment and owner negligence.
      Ectoparasites are not only nuisances to both cats and owners, but they are also
      significant carriers of disease. Therefore, the implementation of rigorous, safe
      preventive measures is of great importance.

PMID- 21181197
TI  - The evaluation of gnathiid (Crustacea: Isopoda: Gnathidae) parasitism in
      goldblotch grouper (Epinephelus costae Staindahner, 1878) in the northeastern
      Mediterranean Sea using the self-organizing map (SOM).
AB  - The self-organizing map (SOM), which is widely used in economics and engineering
      applications, is a type of artificial neural network trained without supervision.
      SOM is used to represent multidimensional data in much lower dimensional spaces
      usually in two dimensions (2D)-while preserving the topological properties of the
      input space. In this study, 2D maps were produced by using SOM to display the
      relationship between seasons, length, weight, and isopod infestation of
      goldblotch grouper (Epinephelus costae Staindahner, 1878). This is first study of
      gnathiid isopod praniza larvae infesting goldblotch grouper (E. costae
      Staindahner, 1878) in the northeast Mediterranean Sea (36 degrees 36' N-36
      degrees 07' E, 35 degrees 52' N-36 degrees 25' E) in Iskenderun Bay. Fish were
      sampled monthly from Iskenderun Bay for a period of 12 months from 2006 May to
      2007 April (Nt=331, Wt+/-SD (range)=392.92+/-72.76 g (169-927 g) TLt+/-SD
      (range)=30.85+/-3.88 cm)). Gnathia sp. was only extracted from the epithelium of
      the buccal cavity and internal side of the gills arch. The monthly patterns in
      infested fish samples (Np=109, Wp+/-SD (range)=349.25+/-182.79 g (169-853 g)
      TLt+/-SD (range)=26.05+/-12.68 cm (18.2-45.0 cm)) infestation rates (mean
      prevalence, P=28.12% (0-60) and mean intensity (MI+/-SD=23.69+/-14.78 (4-82), the
      relationship between length-weight and infested/non-infested fish were
      calculated. Although the gnathiid parasite high intensities were observed in
      fish, there was no significant effect on the growth and general health condition
      of infested fish.

PMID- 21181198
TI  - DFNB89, a novel autosomal recessive nonsyndromic hearing impairment locus on
      chromosome 16q21-q23.2.
AB  - DFNB89 is a novel autosomal recessive nonsyndromic hearing impairment (ARNSHI)
      locus that was mapped to 16q21-q23.2. Linkage to the region was established by
      carrying out genome-wide linkage scans in two unrelated, consanguineous Pakistani
      families segregating ARNSHI. The maximum multipoint LOD score is 9.7 for both
      families and for each family, a significant maximum LOD score of 6.0 and 3.7 were
      obtained. The 3-unit support interval and the region of homozygosity for the two
      families extend from rs717293 (chr16: 62.1 Mb) to rs728929 (chr16: 78.2 Mb) and
      contain 16.1 Mb of sequence. A total of 146 genes are within the DFNB89 interval.
      Eight candidate genes, CALB2, CDH1, CDH3, CDH11, HAS3, NOB1, PLEKHG4 and SMPD3,
      were sequenced, but no potentially causal variants were discovered. DFNB89 is the
      second ARNSHI locus mapped to chromosome 16.

PMID- 21181199
TI  - Expression of lymphatic endothelium-specific hyaluronan receptor LYVE-1 in the
      developing mouse kidney.
AB  - Our knowledge of the embryonic development of the lymphatic vessels within the
      kidney is limited. The aim of this study was to establish the time of appearance
      and the distribution of intra-renal lymphatic vessels in the developing mouse
      kidney by using the lymphatic marker, LYVE-1. Kidneys from embryonic day 12 (E12)
      to E18, from neonates at post-natal day 1 (P1) to P21, and from adults were
      studied. In the adult mouse kidney, LYVE-1 was expressed mainly in the lymphatic
      endothelial cells (LECs) and in a subset of endothelial cells in the glomerular
      capillaries. However, in the developing mouse kidney, LYVE-1 was also expressed
      transiently in F4/80(+)/CD11b(-) immature macrophages/dendritic cells and in the
      developing renal vein. LYVE-1(+) lymphatic vessels connected with extra-renal
      lymphatics were detected in the kidney at E13. F4/80(+)/CD11b(-)/LYVE-1(+)
      immature macrophages/dendritic cells appeared prior to the appearance of LYVE
      1(+) renal lymphatic vessels and were closely intermingled or even formed part of
      the lymphatic vascular wall. Prox1 was expressed only in the LYVE-1(+) LECs from
      fetus to adult-hood, but not in LYVE-1(+) endothelial cells of the developing
      renal vein and macrophages/dendritic cells. Thus, lymphatic vessels of the kidney
      might originate by extension of extra-renal lymphatics through an active
      branching process possibly associated with F4/80(+)/CD11b(-)/LYVE-1(+)
      macrophages/dendritic cells.

PMID- 21181200
TI  - Video-assisted thoracoscopic solitary pulmonary nodule resection after CT-guided
      hookwire localization: 43 cases report and literature review.
AB  - BACKGROUND: Peripheral subpleural solitary pulmonary nodules can be visualized
      and resected easily at thoracoscopy, but it is very difficult to localize deep
      nonpalpable pulmonary nodules that lie in lung parenchyma. The purpose of this
      article was to study the effectiveness of video-assisted thoracoscopic solitary
      pulmonary nodules resection after computed tomography (CT)-guided hookwire
      localization and to review the literature related to solitary pulmonary nodule
      diagnosis and treatment. METHODS: From April 2008 to June 2009, 43 patients with
      a solitary pulmonary nodule who had undergone CT-guided hookwire localization and
      video-assisted thoracoscopic surgery (VATS) were studied. RESULTS: Two cases were
      considered unsuccessful, other patients underwent CT-guided hookwire localization
      successfully, and ten patients had an asymptomatic minimal pneumothorax that did
      not require any intervention. The diameter of nodules ranged from 5 to 30 mm as
      measured by CT (mean 17.2+/-7.5 mm). The distance between the center of nodule
      and visceral pleural ranged from 2 to 40 mm (mean 18.5+/-9.3 mm). Of the 41
      scheduled VATS procedures, 38 patients underwent thoracoscopic wedge resection.
      Twenty-two of 41 patients who revealed primary lung cancer after frozen-section
      examination underwent VATS lobectomy and lymphadenectomy. Three patients were
      converted to thoracotomy, and a major postoperative hemothorax occurred in one
      patient. No intra- or postoperative mortality or morbidity was recorded.
      CONCLUSIONS: Video-assisted thoracoscopic solitary pulmonary nodule resection
      after CT-guided hookwire localization is a safe and effective procedure for
      accurate diagnosis and resection of indeterminate solitary pulmonary nodules.

PMID- 21181201
TI  - Transvesical peritoneoscopy with rigid scope: feasibility study in human male
      cadaver.
AB  - BACKGROUND: Transvesical port refers to the method of accessing the abdominal
      cavity through a natural orifice (i.e., urethra) under endoscopic visualization.
      Since its introduction in 2006, various reports have been published describing
      different surgical interventions using a rigid ureteroscope in a porcine model.
      The aim of this study was to test the access and feasibility of peritoneoscopy by
      using a rigid ureteroscope in a human male cadaver. METHODS: Two adult male
      cadavers were used to perform the procedures. A rigid ureteroscope was used for
      the creation of transvesical access into the peritoneal cavity. Peritoneoscopy,
      liver biopsy, and identification and manipulation of the ileocecal appendix were
      performed. RESULTS: Transvesical access into the peritoneal cavity was quickly
      established. The rigid ureteroscope easily allowed visualization of the abdominal
      cavity with good image quality. Liver biopsy and manipulation of ileocecal
      appendix were carried out without difficulties. CONCLUSIONS: Peritoneoscopy,
      liver biopsy, and ileocecal appendix manipulation using a rigid ureteroscope
      through a transvesical port is feasible in a cadaver model. The development of a
      specific rigid scope for the transvesical port might herald a promising future
      for this NOTES access.

PMID- 21181202
TI  - Downregulation of leptin and resistin expression in blood following bariatric
      surgery.
AB  - BACKGROUND: Type 2 diabetes (T2D) resolves rapidly after bariatric surgery, even
      before substantial weight is lost. However, the molecular pathways underlying
      this phenomenon remain unclear. Microarray data has shown that numerous genes are
      differentially expressed in blood after bariatric surgery, including resistin and
      leptin. Resistin and leptin are circulating hormones derived from adipose tissue,
      which are associated with obesity and insulin resistance. This study examined
      expression of these genes before and after bariatric surgery in diabetic and
      nondiabetic obese patients. METHODS: The study included 16 obese patients who
      underwent bariatric surgery, either Roux-en-Y gastric bypass (RYGB) or adjustable
      gastric banding. Eight patients had T2D. Preoperative blood samples were
      collected in PAXgene tubes to stabilize mRNA. Postoperative samples were
      collected 3 months after surgery. Total RNA was isolated and cDNA was
      synthesized. Real-time quantitative PCR was used to quantify mRNA. Results were
      analyzed using Student's t test with a P<0.05 considered significant. RESULTS:
      Postoperatively, five diabetic patients had discontinued hypoglycemic medications
      and one showed improved glycemic control. Both leptin and resistin mRNA levels
      were elevated in the diabetic group but decreased after surgery to levels near
      those of the nondiabetic group. Greater downregulation of resistin and leptin
      expression occurred in patients who lost more excess body weight (EBW), while
      patients who lost less than 10% EBW had a mean increase in expression of the two
      genes. Downregulation of both genes was more pronounced after RYGB compared to
      gastric banding. CONCLUSIONS: Downregulation of resistin and leptin gene
      expression after bariatric surgery may play a role in normalizing obesity
      associated insulin resistance. Interestingly, downregulation is greater after
      RYGB and in patients who lose a greater proportion of EBW. Targeted therapies for
      obesity and diabetes may be developed by understanding the pathways by which
      these adipocytokines contribute to obesity and T2D.

PMID- 21181203
TI  - Plasma levels of angiostatin and endostatin remain unchanged for the first 3
      weeks after colorectal cancer surgery.
AB  - INTRODUCTION: Angiostatin and endostatin are endogenous inhibitors of
      angiogenesis with anticancer effects. After minimally invasive colorectal
      resection (MICR), blood levels of the proangiogenic factors vascular endothelial
      growth factor (VEGF) and angiopoetin 2 (Ang-2) are elevated for 2-4 weeks. Also,
      postoperative human plasma from weeks 2 and 3 after MICR has been shown to
      stimulate endothelial cell proliferation and migration, which are critical to
      angiogenesis. This proangiogenic state may stimulate tumor growth early after
      MICR. Surgery's impact on angiostatin and endostatin is unknown. This study's
      purpose is to determine perioperative plasma levels of these two proteins in
      colorectal cancer (CRC) patients undergoing MICR. METHODS: Endostatin levels were
      assessed in 34 CRC patients and angiostatin levels in 30 CRC patients. Blood
      samples were taken preoperatively and on postoperative day (POD) 1 and 3 in all
      patients; in a subset, samples were taken between POD 7 and 20. The late samples
      were bundled into 7-day blocks (POD 7-13, POD 14-20) and considered as single
      time points. Angiostatin and endostatin plasma levels were determined via enzyme
      linked immunosorbent assay (ELISA) in duplicate. Wilcoxon signed-rank test and
      Student's t test were used to analyze endostatin and angiostatin data,
      respectively. Significance was set at P<0.0125 (after Bonferroni correction).
      RESULTS: There was a significant decrease in median plasma endostatin levels on
      POD 1, which returned to the preoperative level by POD 3. There was no
      significant difference between pre- and postoperative plasma angiostatin levels.
      CONCLUSIONS: MICR has a very transient impact on plasma levels of endostatin and
      no impact on angiostatin during the first 21 days following surgery. Thus,
      angiostatin and endostatin do not likely contribute to or inhibit the persistent
      proangiogenic changes noted after MICR.

PMID- 21181204
TI  - NOTES cholecystectomy: matched-pair analysis comparing the transvaginal hybrid
      and conventional laparoscopic techniques in a series of 216 patients.
AB  - BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) is currently
      a very important topic for both gastroenterologists and surgeons. We have
      developed a technique of transvaginal hybrid NOTES cholecystectomy (TVC) that
      leaves no visible scar and is applicable to daily use. This technique is compared
      to the conventional laparoscopic cholecystectomy (CLC) in a matched-pair
      analysis. METHODS: From June 2007 until February 2009, 108 NOTES
      cholecystectomies were performed. For a matched-pair analysis we first selected a
      group of 192 female patients who had undergone CLC and who were operated on by
      the same group of surgeons in the same time period. Then 108 pairs who had TVC
      were matched according to the degree of inflammation of the gallbladder and age.
      We were able to contact 208 patients at least 3 months after surgery. Hence, the
      study analysis was performed with 100 complete pairs. RESULTS: All 200
      cholecystectomies were performed successfully without conversion. The TVC
      procedure was significantly longer than CLC (52 vs. 35 min, p<0.001). There were
      no intraoperative complications in either group. There were no significant
      differences with respect to reoperations, wound infections, consumption of
      analgesic drugs, length of hospital stay, and sick leave. Seventy-five TVC and 73
      CLC patients had sexual intercourse after the operation without any complaints.
      CONCLUSION: We present here the largest series of NOTES for cholecystectomy
      published to date and the first comparative study with the gold standard. The TVC
      technique is as successful as the CLC, it causes no more complications than CLC,
      especially with respect to the vaginal approach, it is more time-consuming to
      perform, but has an ideal cosmetic result, i.e., no visible scar.

PMID- 21181205
TI  - Favorable outcomes with laparoscopic surgery for rectal cancer.

PMID- 21181206
TI  - Influenza vaccine after pediatric kidney transplant: a Midwest Pediatric
      Nephrology Consortium study.
AB  - The main aim of this study was to compare the response to trivalent inactivated
      influenza vaccine in children who received a kidney transplant and were on
      steroid-free versus steroid-based immunosuppression. Groups: 1. Kidney transplant
      recipients on steroid-free immunosuppression (n=27); 2. Kidney transplant
      recipients on steroid-based immunosuppression (n=39); 3. Healthy controls (n=21).
      Hemagglutination inhibition titers against 2007-2008 A/H1N1 and A/H3N2 and B
      strains were measured before and 8 weeks postvaccination. Postvaccination
      geometric mean titers to A/H1N1 were significantly lower among both transplant
      groups than controls (p=0.025 and 0.015, respectively). Postvaccination titers to
      H3N2 and B strains were not statistically different between groups. Proportions
      of participants developing seroprotection were not different among groups. Both
      kidney transplant groups seroconverted less than controls for A/H1N1 (p=0.0002)
      and were no different from controls for B. For A/H3N2, the steroid-free group had
      the weakest seroconversion (p=0.008), possibly due to mycophenolate-enhanced
      exposure and a younger age. Overall, children after kidney transplantation
      demonstrated a good serologic response to the inactivated influenza vaccine
      although somewhat lower than controls. Steroid-free immunosuppression did not
      seem to present an advantage in antibody response. Data on inactivated influenza
      vaccine safety and efficacy was collected and demonstrated absence of acute
      rejection or laboratory-proven influenza for 6 months postvaccination.

PMID- 21181208
TI  - Pathogenesis, diagnosis and management of hyperkalemia.
AB  - Hyperkalemia is a potentially life-threatening condition in which serum potassium
      exceeds 5.5 mmol/l. It can be caused by reduced renal excretion, excessive intake
      or leakage of potassium from the intracellular space. In addition to acute and
      chronic renal failure, hypoaldosteronism, and massive tissue breakdown as in
      rhabdomyolysis, are typical conditions leading to hyperkalemia. Symptoms are non
      specific and predominantly related to muscular or cardiac dysfunction. Treatment
      has to be initiated immediately using different therapeutic strategies to
      increase potassium shift into the intracellular space or to increase elimination,
      together with reduction of intake. Knowledge of the physiological mechanisms of
      potassium handling is essential in understanding the causes of hyperkalemia as
      well as its treatment. This article reviews the pathomechanisms leading to
      hyperkalemic states, its symptoms, and different treatment options.

PMID- 21181210
TI  - Breakthrough pain: a qualitative study involving patients with advanced cancer.
AB  - CONTEXT: Breakthrough cancer pain is associated with a high burden of physical,
      psychological and social problems in quantitative studies. Individual experiences
      of living with breakthrough pain have not been studied. OBJECTIVES: This study
      aims to explore the individual experience of living with breakthrough cancer pain
      using a qualitative methodology. METHODS: In depth semi-structured interviews
      were conducted in ten patients with breakthrough cancer pain, and a qualitative
      content analysis was performed. RESULTS: The overarching themes that emerged were
      daily living, communication with health care professionals and management of
      breakthrough pain. CONCLUSIONS: Recognising the impact of breakthrough pain and
      the issues expressed by patients regarding communication and medication gives the
      clinician a framework for assessment and intervention.

PMID- 21181207
TI  - Markers of childhood lupus nephritis indicating disease activity.
AB  - Current treatment regimens for childhood lupus nephritis (LN) are associated with
      significant side-effects and toxicity in vulnerable phases of growth and
      development. The paucity of biomarkers particularly in childhood impedes the
      appropriate clinical management and the development of new therapeutics. We
      analyzed markers of immune system (BAFF, RANTES), complement (Bb, C1q, C3d-CIC,
      C5a) and endothelial cell activation (sVCAM-1) in children with LN (n=22, mean
      age 14.8+/-4.7 years), nephrotic syndrome (n=13) and age-matched healthy controls
      (n=20) to define parameters that correlate with LN activity. Complement fragments
      of the alternative (Bb, p=0.0004) classical (C3d-CIC, p<0.0001) and common
      pathway (C5a, p<0.0001) and the levels of BAFF (p<0.0001), RANTES (p=0.0002) and
      sVCAM-1 (p=0.0004) were significantly higher in active compared to inactive LN.
      Activation of complement was associated with the occurrence of anti-C1q
      antibodies and reduced complement C1q. Complement-activation fragments highly
      correlated with the markers for immune system and endothelial cell activation.
      The ensemble of these parameters may be of great value in identifying early
      flares or remissions of childhood LN, and moreover may prove useful in the
      assessment of new treatments and in determining the optimization of their use.

PMID- 21181211
TI  - Induction of microsomal triglyceride transfer protein expression is a candidate
      mechanism by which ezetimibe therapy might exert beneficial effects in patients
      with nonalcoholic steatohepatitis.

PMID- 21181212
TI  - Clevudine-induced viral response, associated with continued reduction of HBsAg
      titer, was durable after the withdrawal of therapy.
AB  - BACKGROUND: This study was conducted to evaluate the durability of clevudine
      induced viral response after the withdrawal of treatment. METHODS: Patients who
      showed a complete response [alanine aminotransferase (ALT) normalization and
      hepatitis B virus (HBV) DNA <4,700 copies/mL for hepatitis B envelope antigen
      (HBeAg)-negative patients; ALT normalization, HBV DNA <4,700 copies/mL, and HBeAg
      seroconversion for HBeAg-positive patients] in the previous clevudine phase III
      trials were followed for an additional 96 weeks without any treatment for
      hepatitis B. RESULTS: Of the 63 patients in the study cohort, 73% and 35% of the
      patients had HBV DNA <141,500 and <4,700 copies/mL, respectively, and 75% of the
      patients had normal ALT at the end of follow-up. HBeAg seroconversion was
      maintained in 81% of the patients and hepatitis B surface antigen (HBsAg) loss
      occurred in 3 patients. Continued HBsAg titer decrease (-0.5 log IU/mL) was
      observed in the sustained viral responders, suggesting the reduction of
      covalently closed circular DNA in hepatocytes. CONCLUSIONS: The clevudine-induced
      viral response was durable in the majority of patients for 2 years after the
      withdrawal of treatment.

PMID- 21181213
TI  - Mini-open anterior instrumentation with diaphragm sparing for thoracolumbar
      idiopathic scoliosis: its technique and clinical results.
AB  - The traditional method of thoracoabdominal retroperitoneal approach requires
      dissection of diaphragm which bears potential complications such as
      postoperatively weakened abdominal breathing and dysfunction of diaphragm. Mini
      open anterior instrumentation with diaphragm sparing is designed to minimize the
      damage to diaphragm and improve cosmesis. This study compared the traditional
      anterior instrumentation and mini-open anterior instrumentation under the
      hypothesis that both results in similar surgical outcomes in treating
      thoracolumbar scoliosis. In Group A, 38 patients with an average age of 16.5
      years underwent mini-open anterior instrumentation with diaphragm sparing. The
      average standing coronal Cobb angle was 56.4 degrees  in Group A. Thirty-eight
      patients with average age of 16.7 years in Group B received traditional open
      approach. The preoperative average Cobb angle was 55.8 degrees  in Group B. The
      average correction rate of coronal curve was 78% in group A while 75% in group B.
      No statistical difference between the two groups in terms of coronal curve
      correction, sagittal profile restoration and estimated blood loss was observed.
      The operation time was significantly higher in Group A than that in Group B. All
      patients in the two groups had good healing of incisions without neurological and
      instrumental complications during minimal 2 year follow-up. In Groups A and B,
      two patients suffered from pleural effusion, respectively. The wedging of the
      vertebral discs distal to the lowest fused level occurred in three and four
      patients in Group A and B, respectively. One case in group B was found to be
      suspicious pseudoarthrosis without loss of correction. Mini-open anterior
      instrumentation with diaphragm sparing could minimize the surgical invasion as
      well as achieve similar clinical outcomes compared with classical anterior
      approach.

PMID- 21181214
TI  - Proliferative and mineralogenic effects of insulin, IGF-1, and vanadate in fish
      osteoblast-like cells.
AB  - Fish have recently been recognized as a suitable model and a promising
      alternative to mammalian systems to study skeletogenesis. In this regard, several
      fish bone-derived cell lines have been developed and are being used to
      investigate mechanisms associated with insulin-like action of vanadium on
      extracellular matrix (ECM) mineralization. Although proliferative and
      mineralogenic effects of vanadate, insulin-like growth factor 1 (IGF-1), and
      insulin have recently been evaluated in a fish prechondrocyte cell line, no data
      are available in fish bone-forming cells, the osteoblasts. Using fish
      preosteoblast cells, we showed that IGF-1, but not insulin or vanadate,
      stimulated cell proliferation through the mitogen-activated protein kinase (MAPK)
      pathway, while both IGF-1 and vanadate inhibited cell differentiation/ECM
      mineralization through the same mechanism. Our data also indicated that the
      phosphatidyl inositol-3 kinase (PI-3K) pathway stimulates differentiation/ECM
      mineralization in osteoblasts and could represent a way to balance MAPK pathway
      action. The comparison of these new data obtained in fish with those available in
      mammals clearly evidenced a conservation of regulatory mechanisms among
      vertebrate bone-derived systems, although different players are involved.

PMID- 21181215
TI  - Bond of acrylic teeth to different denture base resins after various surface
      conditioning methods.
AB  - The study examined the bond between different denture base resins and highly
      cross-linked acrylic denture teeth with different base surface-conditioning
      methods. One hundred fifty highly cross-linked resin denture teeth (SR-Antaris,
      No. 11, Ivoclar-Vivadent, FL) were divided into five groups with different
      surface-conditioning methods of the base surfaces of the teeth (C = control, no
      surface conditioning, MM = application of methyl methacrylate monomer, SB = sand
      blasting, SBB = sand blasting + bonding agent, TSS = tribochemical silica coating
      + silanization). Teeth were bonded to either a cold-cured denture base resin
      (ProBase Cold, Ivoclar-Vivadent, FL) or heat-cured denture base resins (SR Ivocap
      Plus, Ivoclar-Vivadent, FL and Lucitone 199, Dentsply, USA). After 24 h of
      storage in distilled water, compressive load was applied at 90 degrees  on the
      palatal surface of each tooth until fracture. Median failure load ranged between
      103 and 257 N for Probase Cold groups, 91 to 261 N for Lucitone 199, and 149 to
      320 N for SR Ivocap Plus. For Probase Cold, significant highest failure loads
      resulted when teeth were treated with SB, SBB, or TSS. For Lucitone 199,
      significant highest failure loads has been found with MM and TSS treatment. For
      SR Ivocap Plus, highest failure loads resulted using SBB and TSS. Conditioning of
      the base surfaces of the teeth prior to denture base processing is highly
      recommended. Tooth bond is significantly affected by the surface-conditioning
      method and applied denture base resin. Tribochemical silica coating +
      silanization method can be recommended for pre-treatment of teeth applying either
      heat-cured or cold-cured denture base resin.

PMID- 21181216
TI  - A molecular dynamics study on opioid activities of biphalin molecule.
AB  - Molecular dynamics simulations of the biphalin molecule, (Tyr-D-Ala-Gly-Phe
      NH)(2), and the active tetrapeptide hydrazide, Tyr-D-Ala-Gly-Phe-NH-NH(2) were
      performed to investigate the cause of the increased MU and delta receptor binding
      affinities of the former over the latter. The simulation results demonstrate that
      the acylation of the two equal tetrapeptide fragments of biphalin produces the
      constrained hydrazide bridges [Formula: see text] and [Formula: see text], which
      in turn increase the opportunity of conformations for binding to MU or delta
      receptors. Meanwhile, the connection of the two active tetrapeptide fragments of
      biphalin also results in the constrained side chain torsion angle chi(2) at one
      of the two residues Phe. This constrained side chain torsion angle not only
      significantly increases the delta receptor binding affinity but also makes most
      of the delta receptor binding conformations of biphalin bind to the delta
      receptor through the fragment containing the mentioned residue Phe.

PMID- 21181217
TI  - Open inguinal hernia repair with the use of a polyglycolic acid-trimethylene
      carbonate absorbable mesh: a pilot study.
AB  - PURPOSE: Tension-free repair with mesh placement has become the gold standard for
      open inguinal hernia surgery. Traditionally, non absorbable materials have been
      used for mesh manufacture. The purpose of this pilot study was to evaluate the
      efficacy of using a totally absorbable prosthetic mesh for open inguinal hernia
      repair. METHODS: Ten patients with elective inguinal hernias were set to undergo
      open tension-free inguinal hernia repair with the use of polyglycolic acid
      trimethylene carbonate absorbable mesh. In this pilot study, we looked primarily
      at recurrence and chronic pain assessed 1 year after the operation, while
      immediate postoperative complications were also recorded. RESULTS: All patients
      were discharged from the hospital the day after surgery. In three patients (30%),
      a Foley catheter was inserted to relieve symptoms of urinary retention. None of
      the patients had any immediate postoperative complication. At the 1st year follow
      up, none of the patients had clinical signs of recurrence. However, one patient
      experienced intermittent pain in the operated inguinal area. CONCLUSIONS: Open
      inguinal hernia repair with the use of polyglycolic acid-trimethylene absorbable
      mesh proved efficient in the given patient sample. Further studies with a larger
      number of patients and longer follow up are needed in order to confirm the
      possible favourable effects of this mesh type.

PMID- 21181218
TI  - Gender and age impacts on the correlations between hyperuricemia and metabolic
      syndrome in Chinese.
AB  - Prevalence of both metabolic syndrome (MS) and hyperuricemia are increasing.
      However, findings regarding their relationships are inconsistent. We aimed to
      explore correlations between MS and hyperuricemia in a large Chinese population,
      emphasizing the impacts from gender and age. Data analyses were performed in
      17,762 subjects randomly recruited from Tianjin municipality in China.
      Hyperuricemia was defined as serum uric acid (SUA) >420 MUmol/L for men, >360
      MUmol/L for women. MS was diagnosed by the consensus criterion released in 2009
      from a joint collaboration between American Heart Association and other
      organizations. MS was also diagnosed by Chinese Diabetes Society (CDS) criterion.
      Total hyperuricemic prevalence was 12.16%, with male significantly higher than
      female. Total MS prevalence by consensus criterion was much higher than by CDS
      criterion (25.56% versus 14.09%). Correlation coefficients were much greater in
      women than in men. SUA was significantly positively related with body mass index
      and waist circumference. Generally, binary logistic regression models disclosed
      females with high SUA were twice likely to suffer from MS than males. Young
      females (<=44 years old) with hyperuricemia had the highest odd ratio of 7.857 by
      consensus criterion; and after further adjustment by body mass index, this odd
      ratio was 3.040. SUA and MS were much more closely related in females than in
      males. Young women with hyperuricemia had the highest risk of MS.

PMID- 21181219
TI  - Delivery of paediatric rheumatology care in the UK--the projected shortfall.
AB  - Adult rheumatologists in the UK have historically provided a significant
      contribution to clinical care for children with rheumatic disease. However,
      changes in postgraduate training have resulted in adult rheumatology trainees no
      longer being trained in paediatric rheumatology (PRh), and accordingly, they will
      be ill-equipped to manage children when incumbent adult rheumatology specialists
      retire. The objectives of this work were to ascertain the number of UK adult
      rheumatologists currently involved in PRh care and to inform future workforce
      planning. As part of the British Society for Rheumatology annual consultant
      workforce survey, additional questions relating to PRh were included. A
      questionnaire was sent to 584 adult rheumatologists, of whom 403 (69%) responded
      to questions about PRh; of these, 75 of 403 (19%) reported seeing children and
      many will retire in the next 5 and 10 years (13/75 (18%) and 35/75 (48%),
      respectively). The majority (58/75, 78%) reported having separate clinics for
      children, often alongside other health care professionals (mostly consultant
      paediatrician, paediatric rheumatologist, or allied health professional).
      Notably, 4 of 75 (5%) adult rheumatologists had clinical sessions seeing children
      without any paediatric input. The median (IQR) number of paediatric consultations
      by adult rheumatologists per month was 10 (6, 15), equating to a total 931
      paediatric consultations per average month. Many UK adult rheumatologists are
      involved in managing paediatric rheumatic disease and many will retire over the
      next 10 years. This will result in a shortfall in clinical provision as their
      replacements in adult rheumatology will not have had appropriate PRh training.
      This projected shortfall needs to be addressed in future workforce planning.

PMID- 21181220
TI  - Th-17 associated cytokines in patients with reactive arthritis/undifferentiated
      spondyloarthropathy.
AB  - We and others have previously shown that IL-17 is elevated in the synovial fluid
      of patients with reactive arthritis (ReA)/undifferentiated spondyloarthropathy
      (uSpA) having acute synovitis. Major source for IL-17 is Th17 cells, which
      differentiate from Th0 cells under the influence of TGF-beta and IL-6, IL1-beta
      and are maintained by IL-21 and 23. There is a paucity of data on these cytokines
      in ReA/uSpA. Thus, we measured the levels of Th-17 differentiating and
      maintaining cytokines in synovial fluid of patients with ReA and uSpA. Fifty
      patients with ReA/uSpA (ReA 24, uSpA 26), 19 patients with rheumatoid arthritis
      (RA) and 11 patients with osteoarthritis (OA) were included in the study.
      Synovial fluid (SF) were collected from knee joint and stored at -80 degrees C
      until analysis. Cytokines were assayed using ELISA in SF specimens. The median IL
      17A levels were significantly elevated in ReA (48.3 pg/ml) and uSpA (32.5 pg/ml)
      as compared to non-inflammatory OA controls (<7.8 pg/ml; p < 0.0001), while
      comparable to RA (57.9 pg/ml). Further, IL-6 median values were higher in ReA
      (25.2 ng/ml) and uSpA (13.6 ng/ml) as compared to OA (0.76 ng/ml; p < 0.0001),
      and comparable to RA (15.8 ng/ml). The median levels of IL-1beta, IL-21 levels
      were elevated in ReA, uSpA and RA as compared to OA but were not statistically
      significant. TGF-beta levels in ReA and uSpA were similar to OA but lower than in
      RA (4340 pg/ml; p < 0.05). IL-23 was not detectable in any synovial fluid sample.
      However, levels of these cytokines did not correlate with disease activity
      parameters. Significant positive correlation was observed between IL-17 and IL
      1beta (r = 0.38, p < 0.005), IL-17 and IL-6 (r = 0.659, p < 0.0001), and IL-1beta
      and IL-6 (r = 0.391, p < 0.0001) in ReA and uSpA group. Inflammatory synovitis in
      ReA/uSpA is mediated by pro-inflammatory cytokines like IL-17, IL-6, IL-1beta,
      and IL-21. However, IL-23 was not detectable in SF. Good correlation between IL
      17, IL-6, and IL 1beta suggest that either they are co-regulated or they regulate
      each other.

PMID- 21181221
TI  - Observational studies: a valuable source for data on the true value of RA
      therapies.
AB  - The validity of observational studies is sometimes questioned because of the
      limitations of non-randomly assigned controls, various biases such as channeling
      bias, confounding by indication, and other pitfalls. Yet, (post-marketing)
      observational data can provide important information regarding not only drug
      safety but also the effectiveness and appropriate use of agents in the real
      world, outside of clinical trials. Observational studies also provide data
      regarding the wider value of these agents in terms of, for example, reducing the
      need for surgical procedures, reducing absenteeism and increasing productivity.
      Importantly, data from some observational registry studies have subsequently been
      confirmed by clinical trials, supporting the overall validity of the registry
      based approach. Observational studies also allow measures such as health
      assessment questionnaire scores, disease activity scores, and glucocorticoid use
      over time to be monitored for longer periods. Furthermore, observational data in
      real, less strictly selected patients without the constraints of formal study
      populations may produce findings not observed in clinical trials but that warrant
      further investigation in a controlled trial environment. For example, recent data
      from the Stockholm tumor necrosis factor follow-up registry in Sweden showed
      increases in the time people worked after initiation of biologics that,
      surprisingly, continued into the fourth and fifth years of treatment--a finding
      not observed with standardized outcomes. Observational studies are truly an
      underappreciated and valuable source of data on the real value of anti-rheumatic
      therapies, and these data are essential for making sound decisions regarding
      coverage and reimbursement.

PMID- 21181222
TI  - Significant pathogens in peritonsillar abscesses.
AB  - Peritonsillar abscesses (PTA) are polymicrobial infections, with a diverse
      aerobic and anaerobic flora. The aim of the present study is to compare
      bacteriologic culture results from patients with PTA to those from patients
      undergoing elective tonsillectomy (clinically non-infected tonsils), to better
      elucidate the pathogenic significance of various isolates. A prospective study
      was conducted on 36 PTA patients undergoing acute tonsillectomy and on 80
      electively tonsillectomised patients. Fusobacterium necrophorum (FN) and
      Streptococcus group A (GAS) were isolated significantly more frequently from the
      tonsillar cores of PTA patients, from both the abscessed (p = 0.001 and p =
      0.046, respectively) and non-abscessed sides (p < 0.001 and p = 0.046,
      respectively), than from the tonsillar cores of electively tonsillectomised
      patients. Our findings indicate that FN and GAS are the prominent pathogens in
      PTA. In patients with PTA, the incidence of FN and GAS isolated from the
      abscessed tonsil was the same as from the non-abscessed contralateral side, and
      the growth was comparable by a semi-quantitative approach. Our findings suggest
      that FN is also of pathogenic importance in acute tonsillitis, and that FN growth
      is not a subsequent phenomenon once an abscess has formed. Our findings further
      suggest that other factors influence the development of PTA.

PMID- 21181223
TI  - CT in post-traumatic hypoperfusion complex--a pictorial review.
AB  - Hypoperfusion complex is an uncommon entity found on computed tomography (CT) of
      blunt trauma. It is more common in children compared to adults. Everyone should
      be aware of this entity to interact with clinicians to aid in triage and
      management of patients in view of poor prognosis. It is also important to prevent
      unnecessary laparotomies by confusing abdominal organ injuries. There are certain
      visceral and vascular findings described on abdominal CT that would alert the
      radiologist for this entity. This pictorial review should increase radiologists'
      awareness and recognition of the CT manifestations of hypoperfusion complex
      before an irreversible state of shock occurs in blunt abdominal trauma.

PMID- 21181224
TI  - Intercellular adhesion molecule-1 plays a critical role in glomerulosclerosis
      after subtotal nephrectomy.
AB  - BACKGROUND: Hyperfiltration in the glomeruli have been considered to be an
      important cause of glomerular injury; however, the role of intercellular adhesion
      molecule (ICAM)-1 in the pathogenesis of glomerulosclerosis is not known.
      METHODS: To elucidate the effects of ICAM-1 depletion on hyperfiltration-induced
      glomerular disorder, we used subtotally nephrectomized ICAM-1(+/+) and ICAM-1(-/
      ) mice. We evaluated macrophage infiltration, mesangial matrix expansion,
      transforming growth factor (TGF)-beta and type IV collagen accumulation in
      glomeruli. RESULTS: Macrophage infiltration into the glomeruli and mesangial
      matrix expansion coincident with increased expression of both ICAM-1 and TGF
      beta, and accumulation of type IV collagen were ameliorated in subtotally
      nephrectomized ICAM-1(-/-) mice compared to ICAM-1(+/+) mice. ICAM-1 depletion
      significantly reduced hyperfiltration-induced glomerular injury after renal
      ablation. CONCLUSIONS: Our present findings suggest that glomerular
      hyperfiltration is the leading cause of glomerulosclerosis, and it is mediated,
      at least in part, by ICAM-1 expression and macrophage infiltration.

PMID- 21181225
TI  - Forward masking in the amplitude-modulation domain for tone carriers:
      psychophysical results and physiological correlates.
AB  - Wojtczak and Viemeister (J Acoust Soc Am 118:3198-3210, 2005) demonstrated
      forward masking in the amplitude-modulation (AM) domain. The present study
      examined whether this effect has correlates in physiological responses to AM at
      the level of the auditory midbrain. The human psychophysical experiment used 40
      Hz, 100% AM (masker AM) that was imposed on a 5.5-kHz carrier during the first
      150 ms of its duration. The masker AM was followed by a 50-ms burst of AM of the
      same rate (signal AM) imposed on the same (uninterrupted) carrier, either
      immediately after the masker or with a delay. In the physiological experiment,
      single-unit extracellular recordings in the awake rabbit inferior colliculus (IC)
      were obtained for stimuli designed to be similar to the uninterrupted-carrier
      conditions used in the psychophysics. The masker AM was longer (500 ms compared
      with 150 ms in the psychophysical experiment), and the carrier and modulation
      rate were chosen based on each neuron's audio- and envelope-frequency
      selectivity. Based on the average discharge rates of the responses or on the
      temporal correlation between neural responses to masked and unmasked stimuli,
      only a small subset of the population of IC cells exhibited suppression of signal
      AM following the masker. In contrast, changes in the discharge rates between the
      temporal segments of the carrier immediately preceding the signal AM and during
      the signal AM varied as a function of masker-signal delay with a trend that
      matched the psychophysical results. Unless the physiological observations were
      caused by species differences, they suggest that stages of processing higher than
      the IC must be considered to account for the AM-processing time constants
      measured perceptually in humans.

PMID- 21181226
TI  - Graft selection in arthroscopic anterior cruciate ligament reconstruction.
AB  - BACKGROUND: anterior cruciate ligament (ACL) surgical reconstruction is performed
      with the use of an autogenic, allogenic or synthetic graft. The document issued
      by the Italian National Guidelines System (SNLG, Sistema Nazionale Linee Guida)
      at the National Institute of Health aims to guide orthopaedic surgeons in
      selecting the optimal graft for ACL reconstruction using an evidence-based
      approach. MATERIALS AND METHODS: A monodisciplinary panel was formed to define a
      restricted number of clinical questions, develop specific search strategies and
      critically appraise the literature using the grading of recommendations
      assessment, development, and evaluation (GRADE) method. The final draft was
      shared by the panel and then sent to four external referees to assess its
      readability and clarity, its clinical relevance and the feasibility of
      recommendations. RESULTS: autograft shows moderate superiority compared with
      allograft, in relation to the relevant outcomes and the quality of selected
      evidence, after an appropriate risk-benefit assessment. Allograft shows higher
      failure rate and higher risk of infection. The panel recommends use of
      autografts; patellar tendon should be the first choice, due to its higher
      stability, while use of hamstring is indicated for subjects for whom knee pain
      can represent a particular problem (e.g., some categories of workers).
      CONCLUSIONS: autograft shows better performance compared with allograft and no
      significant heterogeneity in relation to relevant outcomes. The GRADE method
      allowed collation of all the information needed to draw up the recommendations,
      and to highlight the core points for discussion.

PMID- 21181227
TI  - Analyzing the interplay between single cell rheology and force generation through
      large deformation finite element models.
AB  - In this study, experimental results of single cell spreading between two parallel
      microplates are exploited through finite element modeling. Axisymmetric
      computations at finite strains are performed to extract the mechanical properties
      of the cell which can account for cell shape evolution and traction force
      generation. Our model includes two distinct components representing the cortex
      associated with the bilayer membrane on the one hand, and the rest of the cell on
      the other hand. The former is modeled as a homogeneous hyperelastic material
      described by a slightly compressible Gent strain energy function, while the
      latter is idealized either as a quasi-incompressible Newtonian fluid or as
      another homogeneous hyperelastic material. The kinetics of spreading is ensured
      by a stapling procedure defined from experimental observations. Material
      parameters are then optimized to match the simulation closely with the
      experimental data. In particular, the elastic modulus of the cortex is estimated
      at about 1,000 Pa in both models, while the cell interior is characterized by a
      viscosity of 1,000 Pa.s in the biphasic model, or by an elastic modulus of about
      100 Pa in the hyperelastic one. These results are in good agreement with G(') and
      G('') measurements carried out previously in the same parallel plates setup and
      estimated at the typical rate of cell straining. Moreover, stresses are found to
      concentrate at the edge of the cell-substrate contact area. These observations
      allow explaining the relationship between cell spreading and force increase since
      spreading and the consequent straining of the cell mechanical structure could be
      the source of the force applied by the cell on its substrate. They could also
      explain, in a very simple manner, why force-sensitive focal contacts concentrate
      at the cell edges.

PMID- 21181228
TI  - Recall of tobacco pack health warnings by the population in Ukraine and its
      association with the perceived tobacco health hazard.
AB  - OBJECTIVES: After years of prevalence of smoking increase, Ukraine observes its
      decline. Recent tobacco control measures included smoke-free policies, new
      textual health warnings (THW) since late 2006, ban of outdoor tobacco advertising
      since January 2009 and tobacco tax increase since late 2008. The objective was to
      estimate potential contribution of THW to smoking decline process in Ukraine.
      METHODS: The study is based on a nationwide omnibus survey of 2008 Ukrainian
      adults (18+). OUTCOME MEASURES: quitting smoking after 2006 and perception of
      tobacco-related hazards. To measure the exposure to THW respondents were asked to
      describe the warnings they recall. Multivariate regression analysis was performed
      in SPSS 15.0. RESULTS: Those who considered health hazard of smoking as serious
      were significantly more likely to quit. Male smokers were more likely to perceive
      health hazard if they recalled health warnings 'Smoking is addictive, do not
      start to smoke!' and 'Smokers die early'. CONCLUSIONS: THW reach those groups of
      the population they are aimed to and may potentially result in consequent
      quitting smoking in male smokers.

PMID- 21181229
TI  - Functional and structural determinants of reverse operation in the pH-dependent
      oligopeptide transporter PepT1.
AB  - The functional and structural basis of reverse operation of PepT1 has been
      studied in Xenopus oocytes expressing the wild-type and mutated forms of this
      protein. Using brief pulses from a negative holding potential, wild-type and
      Arg282 mutants exhibit outward currents in the presence of Gly-Gln. The reversal
      potential of these currents is affected by both pH and substrate concentration,
      confirming coupled transport in the wild type and in the mutants as well. Long
      lasting voltage and current-clamp experiments show that the outward currents are
      only temporary, and reflect accumulation and/or depletion effects near the
      membrane. The ability to operate in reverse mode was confirmed in all isoforms by
      intracellular injection of substrate. The role of Arg282 and Asp341 in the
      reverse transport was also investigated using charged substrates. Positive Lys
      Gly (but not Gly-Lys) showed enhanced transport currents in the Arg282 mutants.
      In contrast, negative Gly-Asp and Asp-Gly elicited modest currents in all
      isoforms.

PMID- 21181230
TI  - Evaluation of antioxidative and anti-inflammatory potential of hesperidin and
      naringin on the rat air pouch model of inflammation.
AB  - BACKGROUND: Anti-inflammatory and antioxidative potential of hesperidin and
      naringin was carried out considering the rat air pouch model of inflammation.
      METHODS: Reference dose of hesperidin (H) or naringin (N) or indomethacin (I) was
      administered to the rat air pouches. The pouches were induced by injecting
      sterile air into the intra-scapular region of the rats followed by carrageenan
      (AP + C) administration. Rats injected only with air (AP) served as controls.
      RESULTS: The AP + C group, showed an increase in the exudate lipid peroxidation
      (LPO), reduced glutathione (GSH), TNF-alpha, activity of catalase (CAT), total
      leukocytes and neutrophils along with tissue edema and infiltration of
      inflammatory cells. Increases in tissue nitrite, LPO, GSH, SOD (superoxide
      dismutase) and CAT were recorded. Increased CAT and SGPT with concomitant
      decrease in ALP were observed in serum. When treated with indomethacin (AP + C +
      I), all the alterations in the exudate, tissue and serum shifted towards
      normalcy, except LPO in exudate and nitrite in tissue, while, hesperidin (AP + C
      + H) or naringin (AP + C + N) treatment normalized all the alterations.
      CONCLUSION: It seems that both naringin and hesperidin are anti-inflammatory and
      antioxidative in nature, but hesperidin proved to be better than indomethacin and
      naringin because of more pronounced pharmacological actions without tissue
      toxicity.

PMID- 21181231
TI  - Selective estrogen receptor modulators regulate stromal proliferation in human
      benign prostatic hyperplasia by multiple beneficial mechanisms--action of two new
      agents.
AB  - The existing drugs for benign prostatic hyperplasia (BPH) are partially effective
      with undesirable side-effects; hence new agents acting by different mechanism(s)
      are required as supplements. Modulation of estrogen receptor signaling using
      selective estrogen receptor modulators (SERMs) offers an alternative approach for
      BPH management. Using human BPH-derived stromal cells and tissue explants in
      culture we evaluated two SERMs, DL-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2 H
      1-benzopyran (BP) and Ormeloxifene (Orm) in comparison to Tamoxifen (Tam) and 4
      hydroxytamoxifen (OHT). BP, OHT and Tam were more effective than Orm in reducing
      stromal cell proliferation of human BPH. BP was either equipotent or more
      effective than OHT and Tam in increasing estrogen receptor(ER)-beta, TGFbeta1,
      Fas and FasL, and in decreasing ER-alpha, AR, EGF-R and IGF-I expressions in BPH
      stromal cells. BP, Tam and Orm (1.0 mg/Kg) reduced rat prostate weights by almost
      same extent as Finasteride (Fin, 5.0 mg/Kg); however combination treatment
      (SERM+Fin) was more effective. BP was exceptionally efficient in reducing IGF-1
      and cleaving PARP while combination treatments more effectively increased bax:bcl
      2 ratio. Fin reduced acinar diameter and prostatic DHT level but increased
      testosterone, estradiol (E(2)) and E(2)/T+DHT ratio. SERMs, especially BP,
      reduced epithelial cell height drastically without significantly altering steroid
      hormone levels and E(2)/T+DHT ratio. Combination treatment reduced both acinar
      diameter and epithelial cell height with modest increase in E(2), T and
      E(2)/T+DHT. The study reveals the potential of SERMs per se for BPH management,
      and more effectively in combination with a 5alpha-reductase inhibitor. BP appears
      promising for further evaluation as a drug candidate for BPH and prostate cancer.

PMID- 21181232
TI  - The curcuminoid CLEFMA selectively induces cell death in H441 lung adenocarcinoma
      cells via oxidative stress.
AB  - CLEFMA or 4-[3,5-bis(2-chlorobenzylidene-4-oxo-piperidine-1-yl)-4-oxo-2-butenoic
      acid] is a curcuminoid being developed as an anticancer drug. We recently
      reported that it potently inhibits proliferation of various cancer cells. In this
      project, we investigated the effect of CLEFMA on gene expression profile in H441
      lung adenocarcinoma cells, and studied its mechanism of action. In microarray
      data, we observed a deregulation of genes involved in redox and glutamate
      metabolism. Based on the affected ontologies, we hypothesized that
      antiproliferative activity of CLEFMA could be a result of the induction of
      reactive oxygen species (ROS). We tested this hypothesis by determining the
      levels of glutathione (GSH) and ROS in H441 cells treated with CLEFMA. We
      observed a rapid depletion of intracellular GSH/GSSG ratio. Using a cell
      permeable fluorogenic substrate, we found that CLEFMA significantly induced ROS
      in a time- and dose-dependent manner (p < 0.05). Flow-cytometry with a
      mitochondria-selective fluorescent reporter of ROS indicated that the CLEFMA
      induced ROS was of mitochondrial origin. In contrast to the cancer cells, the
      normal lung fibroblasts (CCL-151) did not show any increase in ROS and were
      resistant to CLEFMA-induced cell death. Furthermore, the addition of
      antioxidants, such as catalase, superoxide dismutase and N-acetylcysteine,
      rescued cancer cells from CLEFMA-induced cell death. Gene expression pathway
      analysis suggested that a transcription factor regulator Nrf2 is a pivotal
      molecule in the CLEFMA-induced deregulation of redox pathways. The immunoblotting
      of Nrf2 showed that CLEFMA treatment resulted in phosphorylation and nuclear
      translocation of Nrf2 in a time-dependent fashion. Based on these results, we
      conclude that induction of ROS is critical for the antiproliferative activity of
      CLEFMA and the Nrf2-mediated oxidative stress response fails to salvage H441
      cells.

PMID- 21181233
TI  - Radiotherapy and temozolomide for newly diagnosed glioblastoma and anaplastic
      astrocytoma: validation of Radiation Therapy Oncology Group-Recursive
      Partitioning Analysis in the IMRT and temozolomide era.
AB  - Since the development of the Radiation Therapy Oncology Group-Recursive
      Partitioning Analysis (RTOG-RPA) risk classes for high-grade glioma, radiation
      therapy in combination with temozolomide (TMZ) has become standard care. While
      this combination has improved survival, the prognosis remains poor in the
      majority of patients. Therefore, strong interest in high-grade gliomas from basic
      research to clinical trials persists. We sought to evaluate whether the current
      RTOG-RPA retains prognostic significance in the TMZ era or alternatively, if
      modifications better prognosticate the optimal selection of patients with similar
      baseline prognosis for future clinical protocols. The records of 159 patients
      with newly-diagnosed glioblastoma (GBM, WHO grade IV) or anaplastic astrocytoma
      (AA, WHO grade III) were reviewed. Patients were treated with intensity-modulated
      radiation therapy (IMRT) and concurrent followed by adjuvant TMZ (n = 154) or
      adjuvant TMZ only (n = 5). The primary endpoint was overall survival. Three
      separate analyses were performed: (1) application of RTOG-RPA to the study cohort
      and calculation of subsequent survival curves, (2) fit a new tree model with the
      same predictors in RTOG-RPA, and (3) fit a new tree model with an expanded
      predictor set. All analyses used a regression tree analysis with a survival
      outcome fit to formulate new risk classes. Overall median survival was 14.9
      months. Using the RTOG-RPA, the six classes retained their relative prognostic
      significance and overall ordering, with the corresponding survival distributions
      significantly different from each other (P < 0.01, chi(2) statistic = 70). New
      recursive partitioning limited to the predictors in RTOG-RPA defined four risk
      groups based on Karnofsky Performance Status (KPS), histology, age, length of
      neurologic symptoms, and mental status. Analysis across the expanded predictors
      defined six risk classes, including the same five variables plus tumor location,
      tobacco use, and hospitalization during radiation therapy. Patients with
      excellent functional status, AA, and frontal lobe tumors had the best prognosis.
      For patients with newly-diagnosed high-grade gliomas, RTOG-RPA classes retained
      prognostic significance in patients treated with TMZ and IMRT. In contrast to
      RTOG-RPA, in our modified RPA model, KPS rather than age represented the initial
      split. New recursive partitioning identified potential modifications to RTOG-RPA
      that should be further explored with a larger data set.

PMID- 21181234
TI  - Primer extension based quantitative polymerase chain reaction reveals consistent
      differences in the methylation status of the MGMT promoter in diffusely
      infiltrating gliomas (WHO grade II-IV) of adults.
AB  - Diffusely infiltrating gliomas (WHO grade II-IV) are the most common primary
      brain tumours in adults. These tumours are not amenable to cure by surgery alone,
      so suitable biomarkers for adjuvant modalities are required to guide therapeutic
      decision-making. Epigenetic silencing of the O(6)-methylguanine-DNA
      methyltransferase (MGMT) gene by promoter methylation has been associated with
      longer survival of patients with high-grade gliomas who receive alkylating
      chemotherapy; and molecular testing for the methylation status of the MGMT
      promoter sequence is regarded as among the most relevant of such markers. We have
      developed a primer extension-based assay adapted to formalin-fixed paraffin
      embedded tissues that enables quantitative assessment of the methylation status
      of the MGMT promoter. The assay is very sensitive, highly reproducible, and
      provides valid test results in nearly 100% of cases. Our results indicate that
      oligodendrogliomas, empirically known to have a relatively favourable prognosis,
      are also the most homogeneous entities in terms of MGMT promoter methylation.
      Conversely, astrocytomas, which are more prone to spontaneous progression to
      higher grade malignancy, are significantly more heterogeneous. In addition, we
      show that the degree of promoter methylation correlates with the prevalence of
      loss of heterozygosity on chromosome arm 1p in the oligodendroglioma group, but
      not the astrocytoma group. Our results may have potentially important
      implications for clinical molecular diagnosis.

PMID- 21181235
TI  - Primary central nervous system primitive neuroectodermal tumors (CNS-PNETs) of
      the spinal cord in children: four cases from the German HIT database with a
      critical review of the literature.
AB  - Approximately 30-50% of patients with intracranial primitive neuroectodermal
      tumors (PNETs) of the central nervous system (CNS) develop spinal metastases. In
      contrast, primary spinal CNS-PNETs are extremely uncommon. The database and study
      records of the German/Austrian brain tumor trials HIT 91, HIT SKK 92, and HIT
      2000 were retrospectively reviewed to describe clinical features, treatment
      modalities, and outcome of children with primary CNS-PNETs of the spinal cord who
      were registered as observational patients. Out of 1,248 patients with
      medulloblastomas or CNS-PNETs registered in the HIT database four patients
      (female, n = 3) with primary CNS-PNETs of the spinal cord were identified. Age at
      diagnosis was 10, 16, 23, and 174 months. Location of primary tumors was medulla
      oblongata-T3, C2-T1, T10-L2, T7-T10. Two patients had metastatic disease at
      diagnosis. Complete and incomplete resection was performed in one patient each,
      whereas two patients underwent a biopsy only. Two patients received chemotherapy
      only, in accordance with the HIT 91 trial (sandwich chemotherapy arm). They
      developed disease progression and died six months after diagnosis. One patient
      was given chemotherapy in accordance with the HIT 2000 trial followed by
      craniospinal radiotherapy and four courses of maintenance chemotherapy. The
      patient is in complete remission almost four years after diagnosis. The fourth
      patient developed disease progression while receiving induction chemotherapy.
      Hence, chemotherapy was switched to a modified Head Start protocol. After three
      cycles he underwent double autologous stem cell transplantation and craniospinal
      irradiation. Forty months after diagnosis the patient is alive and well, but
      surveillance MRIs still show nodular enhancing lesions in the area of the primary
      tumor and intracranial meningeal enhancement. Primary CNS-PNETs of the spinal
      cord probably require multimodal treatment including radiotherapy to achieve
      sustained tumor control.

PMID- 21181236
TI  - The clinical impact of bleeding during oral anticoagulant therapy: assessment of
      morbidity, mortality and post-bleed anticoagulant management.
AB  - Although the risk for bleeding during long-term warfarin therapy is established,
      little is known about the clinical impact following warfarin-associated bleeding
      and the management of anticoagulant resumption after a bleed. We performed a
      retrospective chart review of patients who suffered a warfarin-associated bleed
      that required hospitalization or that occurred during hospitalization. We
      determined the proportion of patients who required a blood product transfusion, a
      surgical or other invasive procedure or admission to an intensive care unit, and
      the duration of hospitalization. We also determined the case-fatality rate of
      bleeding and described post-bleed resumption of anticoagulation. We studied 142
      patients (70 women) hospitalized with warfarin-associated bleeding with a mean
      age of 73 years. The most prevalent sites of bleeding were the gastrointestinal
      tract (40.8%) and urinary tract (14.1%). Of all bleeding episodes, 72 (50.1%)
      were classified as major bleeds. There were 66 (46.4%) patients who required
      either endoscopy, surgery or admission to an intensive care unit, and the mean
      duration of hospitalization was 23 days. The case fatality rate of major bleeding
      was 9.5%. Among patients in whom warfarin was restarted, 8.3% suffered recurrent
      bleeding. Warfarin-associated bleeding appears to confer considerable morbidity
      related to transfusion and hospitalization, approximately 1 in 10 major bleeds
      are fatal, and 1 in 12 patients will re-bleeding after warfarin resumption.

PMID- 21181237
TI  - Induction and suppression of RNA silencing: insights from plant viral infections-
      a BARD workshop report.
AB  - An international workshop on ''Induction and Suppression of RNA Silencing:
      Insights from Plant Viral Infections'' was sponsored by the United States-Israel
      Binational Agricultural Research and Development Fund (BARD) and organized in
      Eilat, Israel in March 2010. The focus of this workshop was on molecular
      mechanisms employed by viruses or their hosts, and their interactions, for the
      regulation of virus-induced silencing and suppression. Several of the talks also
      served as potent reminders of scientific hubris and the need to be attentive to
      earlier results, both for analyses and perspective regarding new findings.

PMID- 21181238
TI  - Icariin induces mouse embryonic stem cell differentiation into beating functional
      cardiomyocytes.
AB  - Icariin, the primary active component of Epimedium extracts, has recently been
      shown to induce cardiomyocyte differentiation of murine embryonic stem (mES)
      cells in vitro. However, as these cardiomyocytes were not functionally
      characterized, the potential application of icariin-induced cardiomyocytes in
      clinical practice remains unclear. Therefore, in this study, we characterized the
      structure and function of icariin-induced cardiomyocytes to evaluate their
      potential application in transplantation for cardiac failure treatment. mES cells
      were cultured as embryoid bodies (EBs) via the direct suspension method in the
      presence of icariin. The protein expression profiles and ultrastructural
      characteristics of mES cell-derived cardiomyocytes were then characterized by
      immunofluorescence and transmission electron microscopy, respectively. In
      addition, the expression of cardiac-specific and calcium handling genes was
      detected by semi-quantitative reverse transcription-polymerase chain reaction (RT
      PCR). Cardiomyocytes induced by icariin treatment expressed the cardiac-specific
      proteins myosin light chain-1v (MLC1v), atrial natriuretic polypeptide (ANP), and
      cardiac troponin I (cTnI). Furthermore, these cells appeared to possess
      myofibrils organized into mature sarcomeres that had formed A and I bands. In
      addition, icariin treatment upregulated the mRNA levels of MLC1v, ANP, cTnI,
      calsequestrin (CSQ), and sodium-calcium exchanger (NCX) in these cells. Icariin
      induces the differentiation of mES cells into beating cardiomyocytes with normal
      structure and function. Therefore, these cells may have promising applications in
      cardiac cell therapy or tissue engineering.

PMID- 21181240
TI  - Effect of ZrN coating by magnetron sputtering and sol-gel processed silica
      coating on titanium/porcelain interface bond strength.
AB  - In this study, a coating technique was applied to improve the bond strength of
      titanium (Ti) porcelain. ZrN coating was prepared by magnetron sputtering, and
      silica coating was processed by a sol-gel method. The treated surfaces of the
      specimens were analyzed by X-ray diffraction, and the Ti/porcelain interface was
      investigated by scanning electron microscopy (SEM) and energy dispersive
      spectroscopy. The coated specimens appeared fully coherent to the Ti substrate.
      The fractured bonding surface was also investigated by SEM. The residual
      porcelain on the metal surface could be observed in the ZrN group and silica
      group, but there was no obvious porcelain remaining in the control group. A three
      point-bending test showed that the bonding strength of the ZrN group (45.99 +/-
      0.65 MPa) was higher than the silica group (37.77 +/- 0.78 MPa) (P < 0.001) and
      control group (29.48 +/- 1.01 MPa) (P < 0.001), while that of the silica group
      was significantly higher than the control group (P < 0.001). In conclusion,
      conditioning the ceramic surface with ZrN and silica coatings resulted in a
      stronger Ti/porcelain bond. ZrN coating by magnetron sputtering was a more
      effective way to improve the bond strength between Ti and porcelain compared with
      sol-gel processed silica coating in this study.

PMID- 21181239
TI  - Joint immobilization inhibits spontaneous hyaline cartilage regeneration induced
      by a novel double-network gel implantation.
AB  - We have recently discovered that spontaneous hyaline cartilage regeneration can
      be induced in an osteochondral defect in the rabbit, when we implant a novel
      double-network (DN) gel plug at the bottom of the defect. To clarify whether
      joint immobilization inhibits the spontaneous hyaline cartilage regeneration, we
      conducted this study with 20 rabbits. At 4 or 12 weeks after surgery, the defect
      in the mobile knees was filled with a sufficient volume of the hyaline cartilage
      tissue rich in proteoglycan and type-2 collagen, while no cartilage tissues were
      observed in the defect in the immobilized knees. Type-2 collagen, Aggrecan, and
      SOX9 mRNAs were expressed only in the mobile knees at each period. This study
      demonstrated that joint immobilization significantly inhibits the spontaneous
      hyaline cartilage regeneration induced by the DN gel implantation. This fact
      suggested that the mechanical environment is one of the significant factors to
      induce this phenomenon.

PMID- 21181241
TI  - Male Phyllotreta striolata (F.) produce an aggregation pheromone: identification
      of male-specific compounds and interaction with host plant volatiles.
AB  - The chrysomelid beetle Phyllotreta striolata is an important pest of Brassicaceae
      in Southeast Asia and North America. Here, we identified the aggregation
      pheromone of a population of P. striolata from Taiwan, and host plant volatiles
      that interact with the pheromone. Volatiles emitted by feeding male P. striolata
      attracted males and females in the field. Headspace volatile analyses revealed
      that six sesquiterpenes were emitted specifically by feeding males. Only one of
      these, however, elicited an electrophysiological response from antennae of both
      sexes. A number of host plant volatiles, e.g., 1-hexanol, (Z)-3-hexen-1-ol, and
      the glucosinolate hydrolysis products allyl isothiocyanate (AITC), 3-butenyl
      isothiocyanate, and 4-pentenyl isothiocyanate also elicited clear responses from
      the antenna. The active male-specific compound was identified as (+)-(6R,7S)
      himachala-9,11-diene by chiral stationary phase gas-chromatography with coupled
      mass spectrometry, and by comparison with reference samples from Abies
      nordmanniana, which is known to produce the corresponding enantiomer. The
      pheromone compound was synthesized starting from (-)-alpha-himachalene isolated
      from Cedrus atlantica. Under field conditions, the activity of the synthetic
      pheromone required concomitant presence of the host plant volatile allyl
      isothiocyanate. However, both synthetic (+)-(6R,7S)-himachala-9,11-diene alone
      and in combination with AITC were attractive in a two-choice laboratory assay
      devoid of other natural olfactory stimuli. We hypothesize that P. striolata
      adults respond to the pheromone only if specific host volatiles are present. In
      the same laboratory set up, more beetles were attracted by feeding males than by
      the synthetic stimuli. Thus, further research will be necessary to reveal the
      components of a more complex blend of host or male-produced semiochemicals that
      might enhance trap attractiveness in the field.

PMID- 21181242
TI  - Pheromone communication in Nasonia vitripennis: abdominal sex attractant mediates
      site fidelity of releasing males.
AB  - Males of the parasitic wasp Nasonia vitripennis (Hymenoptera: Pteromalidae) use a
      substrate-borne sex pheromone to attract virgin females. The pheromone is
      synthesized in the rectal vesicle and deposited via the anus by dabbing movements
      of the abdominal tip. The chemicals attracting the females are composed of a
      mixture (4R,5R- and (4R,5 S)-5-hydroxy-4-decanolides (HDL) being synergized by
      the trace component 4-methylquinazoline (4-MeQ) which is not attractive for
      females when offered alone. Here we show that male pheromone deposits are not
      only attractive to virgin females but also for the releasing males themselves. In
      an olfactometer bioassay, males were strongly attracted by their own pheromone
      markings but were unable to discriminate between their own markings and those
      deposited by other males. Polar fractions of pheromone gland extracts containing
      the HDLs and 4-MeQ were also highly attractive for males. Bioassays using
      synthetic pheromones in natural doses revealed that combinations of HDL/4-MeQ and
      4-MeQ alone attracted males whereas the HDLs alone were behaviorally inactive.
      Furthermore, males did not discriminate between HDL/4-MeQ and 4-MeQ alone. We
      conclude that the trace component 4-MeQ mediates site fidelity of N. vitripennis
      males at sites previously marked with the abdominal sex pheromone. The use of 4
      MeQ to stay at and to return to scent-marked patches rather than marking new ones
      might be a strategy to economize semiochemical use in N. vitripennis males.

PMID- 21181244
TI  - Redactable signatures for signed CDA Documents.
AB  - The Clinical Document Architecture, introduced by Health Level Seven, is a XML
      based standard intending to specify the encoding, structure, and semantics of
      clinical documents for exchange. Since the clinical document is in XML form, its
      authenticity and integrity could be guaranteed by the use of the XML signature
      published by W3C. While a clinical document wants to conceal some personal or
      private information, the document needs to be redacted. It makes the signed
      signature of the original clinical document not be verified. The redactable
      signature is thus proposed to enable verification for the redacted document. Only
      a little research does the implementation of the redactable signature, and there
      still not exists an appropriate scheme for the clinical document. This paper will
      investigate the existing web-technologies and find a compact and applicable model
      to implement a suitable redactable signature for the clinical document viewer.

PMID- 21181243
TI  - Volatile emissions from Alnus glutionosa induced by herbivory are quantitatively
      related to the extent of damage.
AB  - Plant volatile organic compounds (VOCs) elicited in response to herbivory serve
      as cues for parasitic and predatory insects. Knowledge about quantitative
      relationships between the extent of herbivore-induced damage and the quantities
      of VOCs released is scarce. We studied the kinetics of VOC-emissions from foliage
      of the deciduous tree Alnus glutinosa induced by feeding activity of larvae of
      the geometrid moth Cabera pusaria. Quantitative relationships between the
      intensity of stress and strength of plant response were determined. Intensity of
      biotic stress was characterized by herbivore numbers (0-8 larvae) and by the
      amount of leaf area eaten. The strength of plant response was characterized by
      monitoring (i) changes in photosynthesis, (ii) leaf ultrastructure, and (iii)
      plant volatiles. Net assimilation rate displayed compensatory responses in
      herbivore-damaged leaves compared with control leaves. This compensatory response
      was associated with an overall increase in chloroplast size. Feeding-induced
      emissions of products of the lipoxygenase pathway (LOX products; (E)-2-hexenal,
      (Z)-3-hexenol, 1-hexanol, and (Z)-3-hexenyl acetate) peaked at day 1 after larval
      feeding started, followed by an increase of emissions of ubiquitous monoterpenes
      peaking on days 2 and 3. The emission of the monoterpene (E)-beta-ocimene and of
      the nerolidol-derived homoterpene 4,8-dimethyl-nona-1,3,7-triene (DMNT) peaked on
      day 3. Furthermore, the emission kinetics of the sesquiterpene (E,E)-alpha
      farnesene tended to be biphasic with peaks on days 2 and 4 after start of larval
      feeding. Emission rates of the induced LOX products, of (E)-beta-ocimene and
      (E,E)-alpha-farnesene were positively correlated with the number of larvae
      feeding. In contrast, the emission of DMNT was independent of the number of
      feeders. These data show quantitative relationships between the strength of
      herbivory and the emissions of LOX products and most of the terpenoids elicited
      in response to feeding. Thus, herbivory-elicited LOX products and terpenoid
      emissions may convey both quantitative and qualitative signals to antagonists of
      the herbivores. In contrast, our data suggest that the feeding-induced
      homoterpene DMNT conveys the information "presence of herbivores" rather than
      information about the quantities of herbivores to predators and parasitoids.

PMID- 21181246
TI  - Synthesis, characterization luminiscence studies and microbial activity of
      ethylenediamine ruthenium (II) complexes with dipyridophenazine ligands.
AB  - Three symmetric ligands 7-methyl dipyrido-[3,2-a;2',3'-c]phenazine (dppz-CH(3)),
      7-nitro dipyrido-[3,2-a;2',3'-c]phenazine (dppz-NO(2)) and benzo[i]dipyrido-[3,2
      a;2',3'-c]phenazine (dppn) and their ruthenium(II) complexes
      [Ru(en)(2)(L)][ClO(4)](2) (en= ethylenediamine), L= dppz-CH(3), dppz-NO(2) and
      dppn have been synthesized and characterized by IR, (1)H, (13)C NMR and Mass
      spectra. The interactions of these complexes with calf thymus DNA have been
      investigated by spectrophotometric, spectrofluorimetric, circular dichroism,
      viscosity and thermal denaturation studies. As the planar extension of the
      intercalative ligand increases, the interaction of the complex with DNA
      increases, indicating that the size and shape of the intercalalative ligand has a
      marked effect on the strength of interaction. The plot of log K versus log
      [Na(+)] yield a slope of -1.26, -1.53, -1.60 for the complexes 1, 2 and 3
      respectively. These three complexes have been found to promote the cleavage of
      plasmid pBR 322 DNA upon irradiation.

PMID- 21181247
TI  - Seat belt use among overweight and obese adolescents.
AB  - Motor vehicle crashes are the leading cause of death for adolescents. Previous
      studies with adults found an association between weight status and decreased use
      of seat belts. Research has also found significantly higher morbidity and
      mortality rates in obese individuals who are involved in motor vehicle crashes.
      If these relationships hold true in obese adolescents they represent additional
      risk factors for complications from motor vehicle trauma. Given the prevalence of
      obesity in adolescents (17.4%) and the increased risk of harm associated with
      obese individuals involved in motor vehicle crashes, this study explored whether
      there was an association between obesity in adolescents and their use of seat
      belts. Initial investigation found that rarely/never wearing seat belts was
      significantly greater for African Americans (22.6%), 18 years of age or older
      (19.4%), lived with adults other than both parents (15.7%), and males (15.4%).
      Bivariate logistic regression analysis controlling for demographic variables
      found that there was no statistically significant difference between overweight
      and normal weight adolescents. However, obese students were 1.72 times as likely
      as normal weight students to never or rarely wear their seat belts when riding in
      a car as a passenger. In particular, obese females and obese students in the
      middle school age ranges were statistically significantly more likely than normal
      weight students to never or rarely wear their seat belts.

PMID- 21181248
TI  - Assessment of state measures of risk-appropriate care for very low birth weight
      infants and recommendations for enhancing regionalized state systems.
AB  - The goal of this study was to examine state measurements and improvements in risk
      appropriate care for very low birth weight (VLBW) infants. The authors reviewed
      state perinatal regionalization models and levels of care to compare varying
      definitions between states and assess mechanisms of measurement and areas for
      improvement. Seven states that presented at a 2009 Association of Maternal &
      Child Health Programs Perinatal Regionalization Meeting were included in the
      assessment. Information was gathered from meeting presentations, presenters,
      state representatives, and state websites. Comparison of state levels of care and
      forms of regulation were outlined. Review of state models revealed variability in
      the models themselves, as well as the various mechanisms for measuring and
      improving risk-appropriate care. Regulation of regionalization programs, data
      surveillance, review of adverse events, and consideration of geography and
      demographics were identified as mechanisms facilitating better measurement of
      risk-appropriate care. Antenatal or neonatal transfer arrangements, telemedicine
      networks, acquisition of funding, provision of financial incentives, and patient
      education comprised state actions for improving risk-appropriate care. The void
      of explicit and updated national standards led to the current variations in
      definitions and models among states. State regionalization models and measures of
      risk-appropriate care varied greatly. These variations arose from inconsistent
      definitions and models of perinatal regionalization. Guidelines should be
      collaboratively developed by healthcare providers and public health officials for
      consistent and suitable measures of perinatal risk-appropriate care.

PMID- 21181249
TI  - Control of firing patterns by two transient potassium currents: leading spike,
      latency, bistability.
AB  - Transient potassium currents distinctively affect firing properties, particularly
      in regulating the latency before repetitive firing. Pyramidal cells of the dorsal
      cochlear nucleus (DCN) have two transient potassium currents, I(Kif) and I(Kis),
      fast and slowly inactivating, respectively, and they exhibit firing patterns with
      dramatically variable latencies. They show immediate repetitive firing, or only
      after a long latency with or without a leading spike, the so-called pauser and
      buildup patterns. We consider a conductance-based, ten-variable, single
      compartment model for the DCN pyramidal cells (Kanold and Manis 2001). We develop
      and analyze a reduced three-variable integrate-and-fire model (KM-LIF) which
      captures the qualitative firing features. We apply dynamical systems methods to
      explain the underlying biophysical and mathematical mechanisms for the firing
      behaviors, including the characteristic firing patterns, the latency phase, the
      onset of repetitive firing, and some discontinuities in the timing of latency
      duration (e.i. first spike latency and first inter spike interval). Moreover, we
      obtain new insights associated with the leading spike by phase plane analysis. We
      further demonstrate the effects of possible heterogeneity of I(Kis). The latency
      before repetitive firing can be controlled to cover a large range by tuning of
      the relative amounts of I(Kif) and I(Kis). Finally, we find for the full system
      robust bistability when enough I(Kis) is present.

PMID- 21181250
TI  - Functional assessment and behavioural intervention for eating difficulties in
      children with autism: a study conducted in the natural environment using parents
      and ABA tutors as therapists.
AB  - Two functional assessments (interview and direct observation) were used with
      three children with autism to identify the functions maintaining mealtime
      behaviour including acceptance, mouth clean, refusal, and other disruptive
      behaviours such as crying and pushing the spoon. Based on results of the
      functional assessments it was hypothesized that appropriate and disruptive
      mealtime behaviour was maintained by different contingencies. A non-concurrent
      multiple baseline design across participants was utilized to validate the
      effectiveness of the intervention. Intervention for all participants included
      presentation of food on a spoon for 30 s unless acceptance occurred. Acceptance
      resulted in putative reinforcement. The meal ended after 20 presentations. For
      all participants, acceptance and mouth cleans increased while disruptive
      behaviour decreased, and effects were maintained at follow-up.

PMID- 21181251
TI  - Emotion perception in music in high-functioning adolescents with Autism Spectrum
      Disorders.
AB  - Individuals with Autism Spectrum Disorders (ASD) succeed at a range of musical
      tasks. The ability to recognize musical emotion as belonging to one of four
      categories (happy, sad, scared or peaceful) was assessed in high-functioning
      adolescents with ASD (N = 26) and adolescents with typical development (TD, N =
      26) with comparable performance IQ, auditory working memory, and musical training
      and experience. When verbal IQ was controlled for, there was no significant
      effect of diagnostic group. Adolescents with ASD rated the intensity of the
      emotions similarly to adolescents with TD and reported greater confidence in
      their responses when they had correctly (vs. incorrectly) recognized the
      emotions. These findings are reviewed within the context of the amygdala theory
      of autism.

PMID- 21181252
TI  - Comparison of antiretroviral adherence questions.
AB  - Our objective was to compare antiretroviral adherence questions to better
      understand concordance between measures. Among 53 methadone maintained HIV
      infected drug users, we compared five measures, including two single item
      measures using qualitative Likert-type responses, one measure of percent
      adherence, one visual analog scale, and one multi-item measure that averaged
      responses across antiretrovirals. Responses were termed inconsistent if
      respondents endorsed the highest adherence level on at least one measure but
      middle levels on others. We examined ceiling effects, concordance, and
      correlations with VL. Response distributions differed markedly between measures.
      A ceiling effect was less pronounced for the single-item measures than for the
      measure that averaged responses for each antiretroviral: the proportion with 100%
      adherence varied from 22% (single item measure) to 58% (multi-item measure).
      Overall agreement between measures ranged from fair to good; 49% of participants
      had inconsistent responses. Though responses correlated with VL, single-item
      measures had higher correlations. Future studies should compare single-item
      questions to objective measures.

PMID- 21181253
TI  - An international quality of life instrument to assess wellbeing in adults who are
      HIV-positive: a short form of the WHOQOL-HIV (31 items).
AB  - Few cross-cultural measures are available to assess quality of life (QoL) in
      HIV/AIDS. A short form of the WHOQOL-HIV-the WHOQOL-HIV BREF-was developed and
      tested. Survey data from 1,923 HIV-positive adults (selected for age, gender and
      disease stage) were collected in 8 culturally diverse centres. The 'best' HIV
      specific item was extracted from five HIV facets of the WHOQOL-HIV long form
      using information about item correlations with QoL, health and domains, item
      discriminant validity and centre problems. The five identified items were then
      integrated with the WHOQOL-BREF to complete the 31 item WHOQOL-HIV BREF. This
      short form shows good internal consistency reliability and discriminant validity
      for 'known' disease stages. Confirmatory Factor Analysis showed an overall good
      fit for a six domains model (Comparative Fit Index = 0.97), supporting scoring.
      Quality of life in different cultures is reported. A value of the WHOQOL-HIV
      short form is in monitoring QoL in multi-national clinical trials, and in
      clinical practice.

PMID- 21181255
TI  - Community psychology and global climate change: introduction to the special
      section.
AB  - Global climate change is not just a distant environmental or future problem but a
      crisis that has a clear human face already causing the suffering of millions
      around the globe. It is an issue of high relevance for community psychologists
      and the communities we work with but has received little attention within the
      field of community psychology. This special section is intended to promote more
      thinking and dialogue on this important topic. Six articles are presented that
      feature both theoretical consideration and empirical research related to global
      climate change and related environmental issues.

PMID- 21181254
TI  - Nuclear proteins: finding and binding target sites in chromatin.
AB  - Fluorescent protein labelling, as well as impressive progress in live cell
      imaging have revolutionised the view on how essential nuclear functions like gene
      transcription regulation and DNA repair are organised. Here, we address questions
      like how DNA-interacting molecules find and bind their target sequences in the
      vast amount of DNA. In addition, we discuss methods that have been developed for
      quantitative analysis of data from fluorescence recovery after photobleaching
      experiments (FRAP).

PMID- 21181256
TI  - Composition of heavy metals and airborne fibers in the indoor environment of a
      building during renovation.
AB  - The renovation of a building will certainly affect the quality of air in the
      vicinity of where associated activities were undertaken, this includes the
      quality of air inside the building. Indoor air pollutants such as particulate
      matter, heavy metals, and fine fibers are likely to be emitted during renovation
      work. This study was conducted to determine the concentration of heavy metals,
      asbestos and suspended particulates in the Biology Building, at the Universiti
      Kebangsaan, Malaysia (UKM). Renovation activities were carried out widely in the
      laboratories which were located in this building. A low-volume sampler was used
      to collect suspended particulate matter of a diameter size less than 10 MUm
      (PM10) and an air sampling pump, fitted with a cellulose ester membrane filter,
      were used for asbestos sampling. Dust was collected using a small brush and
      scope. The concentration of heavy metals was determined through the use of
      inductively coupled plasma-mass spectroscopy and the fibers were counted through
      a phase contrast microscope. The concentrations of PM10 recorded in the building
      during renovation action (ranging from 166 to 542 MUg m-3) were higher than the
      value set by the Department of Safety and Health for respirable dust (150 MUg m
      3). Additionally, they were higher than the value of PM10 recorded in indoor
      environments from other studies. The composition of heavy metals in PM10 and
      indoor dust were found to be dominated by Zn and results also showed that the
      concentration of heavy metals in indoor dust and PM10 in this study was higher
      than levels recorded in other similar studies. The asbestos concentration was
      0.0038 +/- 0.0011 fibers/cc. This was lower than the value set by the Malaysian
      Department of Occupational, Safety and Health (DOSH) regulations of 0.1
      fibers/cc, but higher than the background value usually recorded in indoor
      environments. This study strongly suggests that renovation issues need to be
      considered seriously by relevant stakeholders within the university in order to
      ensure that the associated risks toward humans and indoor environment are
      eliminated, or where this is not feasible, minimized as far as possible.

PMID- 21181257
TI  - Monitoring and validating spatio-temporal dynamics of biogeochemical properties
      in Mersin Bay (Turkey) using Landsat ETM+.
AB  - The objective of this study was to devise and validate simple models for
      estimating spatio-temporal dynamics of seven optically (in)active biogeochemical
      properties in Mersin Bay using Landsat 7 Enhanced Thematic Mapper Plus (ETM+)
      data and GIS. Spatio-temporal dynamics of Secchi depth (S (depth)), dissolved
      oxygen (DO), nitrite nitrogen (NO(2)-N), nitrate nitrogen (NO3-N), silicate
      (SiO4), 5-day biological oxygen demand (BOD5), and chlorophyll-a (Chl-a) were
      estimated using best-fit multiple linear regression (MLR) models as a function of
      Landsat 7 ETM+ and ground data in 2007 and 2008, latitude, longitude, and day of
      year. Validation of the MLR models against Landsat and ground data in 2005 led to
      r values ranging from 0.39 for NO2-N (P = 0.008) to 0.79 for S (depth) (P <
      0.001). Parsimonious MLR models built in this study appear to be promising for
      monitoring and predicting spatio-temporal dynamics of optically (in)active water
      quality characteristics in Mersin Bay.

PMID- 21181258
TI  - Monitoring the local distribution of striped hyenas (Hyaena hyaena L.) in the
      Eastern Mediterranean Region of Turkey (Hatay) by using GIS and remote sensing
      technologies.
AB  - Striped hyenas (Hyaena hyaena L.) are one of the large carnivores whose numbers
      have rapidly decreased in Turkey. To monitor and assess the distribution of
      striped hyenas in Mediterranean region of Turkey, geographical information
      systems (GIS) and remote sensing technologies were implemented. For this purpose,
      the GIS database was generated and digital maps were produced in ArcGIS 9.2
      program, considering some of the main factors including signs of striped hyenas,
      elevation, slope, land use types, feeding sources, and road network. The land use
      types in the distribution area of striped hyenas were classified by using ERDAS
      Imagine program. The results from the land use classification indicated that the
      signs of striped hyenas mostly distributed over the agricultural areas especially
      with olive groves, and followed by maquis. It was found that there was a spatial
      relationship between the signs of striped hyenas and feeding sources such as
      organic waste centers and a chicken farm in the region.

PMID- 21181259
TI  - Indoor pesticide application practices and levels in homes of Bangkok
      Metropolitan Region.
AB  - This study investigated the indoor application practices of pesticides in
      different homes located in urban, suburban, and rural areas of the Bangkok
      Metropolitan Region (BMR). A multi-stage stratified-judgmental sampling was
      applied to select 280 representative households in BMR for an in-depth
      questionnaire survey. We found about 71% of these households having mosquitoes as
      their main indoor nuisance. An inventory on the types and active ingredients was
      obtained through a shop-shelf survey. Among 22 available commercial products, 12
      different active ingredients were observed with the pyrethroid containing
      pesticides are the most common. The stepwise regression analysis was conducted to
      reveal the statistical association between indoor levels of total pyrethriods (in
      the air and on the floor surface of homes) and the household application
      practices such as the overlap time period since the last application, application
      and storage locations, and frequency of applications, for instances.

PMID- 21181260
TI  - Surveying drainage culvert use by carnivores: sampling design and cost-benefit
      analyzes of track-pads vs. video-surveillance methods.
AB  - Environmental assessment studies often evaluate the effectiveness of drainage
      culverts as habitat linkages for species, however, the efficiency of the sampling
      designs and the survey methods are not known. Our main goal was to estimate the
      most cost-effective monitoring method for sampling carnivore culvert using track
      pads and video-surveillance. We estimated the most efficient (lower costs and
      high detection success) interval between visits (days) when using track-pads and
      also determined the advantages of using each method. In 2006, we selected two
      highways in southern Portugal and sampled 15 culverts over two 10-day sampling
      periods (spring and summer). Using the track-pad method, 90% of the animal tracks
      were detected using a 2-day interval between visits. We recorded a higher number
      of crossings for most species using video-surveillance (n = 129) when compared
      with the track-pad technique (n = 102); however, the detection ability using the
      video-surveillance method varied with type of structure and species. More
      crossings were detected in circular culverts (1 m and 1.5 m diameter) than in box
      culverts (2 m to 4 m width), likely because video cameras had a reduced vision
      coverage area. On the other hand, carnivore species with small feet such as the
      common genet Genetta genetta were detected less often using the track-pad
      surveying method. The cost-benefit analyzes shows that the track-pad technique is
      the most appropriate technique, but video-surveillance allows year-round surveys
      as well as the behavior response analyzes of species using crossing structures.

PMID- 21181261
TI  - Mercury levels and health parameters in the threatened Olrog's Gull (Larus
      atlanticus) from Argentina.
AB  - Mercury (Hg) exposure was investigated through feathers of Olrog's Gull and
      related to health parameters in adults (hematocrit, total plasma proteins,
      morphometric measures, sex) and chicks (hematocrit, total plasma proteins,
      immunoglobulins G and M) from a colony located in estuary of Bahia Blanca,
      Argentina. Mercury concentrations were 5.50 +/- 2.59 MUg g-1 (n = 44) in live
      adults, 1.85 +/- 0.45 MUg g-1 (n = 45) in live chicks and 1.81 +/- 0.41 MUg g-1
      (n = 41) in dead chicks. Large differences were observed between live adults and
      live or dead chicks and small differences between live and dead chicks. In the
      adults, the sex of the birds was the variable that best explained Hg
      concentrations. Male birds had higher concentrations than females; this suggests
      that the clutch provides a sink for mercury during egg laying. Hg concentrations
      in both adults and live chicks were associated with higher hematocrits. This
      could be associated with upregulated erythropoiesis to compensate for increased
      rate of destruction of prematurely senescent, Hg-contaminated erythrocytes. Based
      on our results, on the levels of Hg pollution in the past in the study area, and
      on the dietary specialization of Olrog's Gull, we must be vigilant about
      potential negative effects of Hg pollution on this population and recommend
      continued monitoring on this threatened species.

PMID- 21181262
TI  - Toxicity evaluation of natural samples from the vicinity of rice fields using two
      trophic levels.
AB  - An ecotoxicological screening of environmental samples collected in the vicinity
      of rice fields followed a combination of physical and chemical measurements and
      chronic bioassays with two freshwater trophic levels (microalgae:
      Pseudokirchneriella subcapitata and Chlorella vulgaris; daphnids: Daphnia
      longispina and Daphnia magna). As so, water and sediment/soil elutriate samples
      were obtained from three sites: (1) in a canal reach crossing a protected wetland
      upstream, (2) in a canal reach surrounded by rice fields and (3) in a rice paddy.
      The sampling was performed before and during the rice culture. During the rice
      cropping, the whole system quality decreased comparatively to the situation
      before that period (e.g. nutrient overload, the presence of pesticides in
      elutriates from sites L2 and L3). This was reinforced by a significant inhibition
      of both microalgae growth, especially under elutriates. Contrary, the life
      history traits of daphnids were significantly stimulated with increasing
      concentrations of water and elutriates, for both sampling periods.

PMID- 21181263
TI  - Convergent synthesis of a common pentasaccharide corresponding to the O-antigen
      of Escherichia coli O168 and Shigella dysenteriae type 4.
AB  - A convenient synthetic strategy of the common acidic pentasaccharide repeating
      unit corresponding to the O-antigen of enterotoxigenic E. coli O168 and Shigella
      dysenteriae type 4 has been successfully developed. A stereoselective [2 + 3]
      block glycosylation method has been exploited to get the target pentasaccharide
      derivative. Most of the synthetic intermediates were solid and prepared in high
      yields from commercially available reducing sugars following a series of
      protection-deprotection reactions. A alpha-D-mannose moiety has been used as the
      source of alpha-D-glucosamine moiety. A late-stage TEMPO mediated selective
      oxidation reaction finally resulted in the pentasaccharide containing a
      glucuronic acid unit.

PMID- 21181264
TI  - Molecular responses transduced by serial oxidative stress in the retinal pigment
      epithelium: feedback control modeling of gene expression.
AB  - The purpose of this study was to characterize the early molecular responses to
      quantified levels of serial oxidative stress (OS) in the human retinal pigment
      epithelium (RPE). Confluent ARPE-19 cells were cultured for 3 days in defined
      medium to stabilize gene expression. The cells were serially exposed to high
      levels of OS (500 MUM H(2)O(2)) with up to 3 distinct stimuli presented 4 h
      apart. Gene expression was followed for at least 8 h following initiation of each
      OS. Using real time qPCR, we quantified the expression of immediate early genes
      from the AP-1 and EGR transcription factor families and other genes involved in
      regulating the redox status of the cells. Significant and quantitative changes
      were seen in the expression of five AP-1 transcription factor genes. The peak
      level of induced transcription from OS varied from two-fold to >64-fold over the
      first 4 h, depending on the gene and magnitude of OS. Serial responses were
      characterized and distinct types of quantifiable OS-specific responses were
      observed. The responses manifested controlled serial increases in expression of
      these genes in a manner dependent upon the rate of increase in transcription, the
      relative duration of the transcriptional stimulus, and the characteristic
      relaxation to the initial steady state. This complexity suggests a mechanism
      whereby the rate of increase in transcription directs alternative paths to effect
      downstream gene-specific responses to OS. The molecular mechanisms by which these
      signals are transduced and controlled in the RPE are speculative. However, the
      rapidity of the TF response, and the known autoregulation of TF promoters by
      their gene products suggests that the early control is likely mediated by
      phosphorylation and activation of existing AP-1 and EGR protein pools within the
      cell, modulated by the opposing activity of kinase and phosphatase enzymes.
      Because of the differences in both initial and serial responses to the input
      stresses, it appears that control theory may provide a useful characterization of
      the distinctions.

PMID- 21181266
TI  - Fas and FasL expression in the spinal cord following cord hemisection in the
      monkey.
AB  - The changes of endogenous Fas/FasL in injured spinal cord, mostly in primates,
      are not well known. In this study, we investigated the temporal changes in the
      expression of Fas and FasL and explored their possible roles in the ventral horn
      of the spinal cord and associated precentral gyrus following T(11) spinal cord
      hemisection in the adult rhesus monkey. A significant functional improvement was
      seen with the time going on in monkeys subjected to cord hemisection. Apoptotic
      cells were also seen in the ventral horn of injured spinal cord with TUNEL
      staining, and a marked increase presents at 7 days post operation (dpo).
      Simultaneously, the number of Fas and FasL immunoreactive neurons in the spinal
      cords caudal and rostral to injury site and their intracellular optical density
      (OD) in the ipsilateral side of injury site at 7 dpo increased significantly more
      than that of control group and contralateral sides. This was followed by a
      decrease and returned to normal level at 60 dpo. No positive neurons were
      observed in precentral gyrus. The present results may provide some insights to
      understand the role of Fas/FasL in the spinal cord but not motor cortex with
      neuronal apoptosis and neuroplasticity in monkeys subjected to hemisection spinal
      cord injury.

PMID- 21181267
TI  - Discrete wavelet-aided delineation of PCG signal events via analysis of an area
      curve length-based decision statistic.
AB  - The aim of this study is to describe a robust unified framework for segmentation
      of the phonocardiogram (PCG) signal sounds based on the false-alarm probability
      (FAP) bounded segmentation of a properly calculated detection measure. To this
      end, first the original PCG signal is appropriately pre-processed and then, a
      fixed sample size sliding window is moved on the pre-processed signal. In each
      slid, the area under the excerpted segment is multiplied by its curve-length to
      generate the Area Curve Length (ACL) metric to be used as the segmentation
      decision statistic (DS). Afterwards, histogram parameters of the nonlinearly
      enhanced DS metric are used for regulation of the alpha-level Neyman-Pearson
      classifier for FAP-bounded delineation of the PCG events. The proposed method was
      applied to all 85 records of Nursing Student Heart Sounds database (NSHSDB)
      including stenosis, insufficiency, regurgitation, gallop, septal defect, split
      sound, rumble, murmur, clicks, friction rub and snap disorders with different
      sampling frequencies. Also, the method was applied to the records obtained from
      an electronic stethoscope board designed for fulfillment of this study in the
      presence of high-level power-line noise and external disturbing sounds and as the
      results, no false positive (FP) or false negative (FN) errors were detected. High
      noise robustness, acceptable detection-segmentation accuracy of PCG events in
      various cardiac system conditions, and having no parameters dependency to the
      acquisition sampling frequency can be mentioned as the principal virtues and
      abilities of the proposed ACL-based PCG events detection-segmentation algorithm.

PMID- 21181265
TI  - Remodeling of sphingolipids by plasma membrane associated enzymes.
AB  - The sphingolipid plasma membrane content and pattern is the result of several
      processes, among which the main, in term of quantity, are: neo-biosynthesis in
      endoplasmic reticulum and Golgi apparatus, membrane turnover with final
      catabolism in lysosomes and membrane shedding. In addition to this, past and
      recent data suggest that the head group of sphingolipids can be opportunely
      modified at the plasma membrane level, probably inside specific membrane lipid
      domains, by the action of enzymes involved in the sphingolipids metabolism,
      working directly at the cell surface. The number of membrane enzymes, hydrolases
      and transferases, acting on membrane sphingolipids is growing very rapidly. In
      this report we describe some properties of these enzymes.

PMID- 21181268
TI  - Psychological distress in refugee children: a systematic review.
AB  - Nearly one-quarter of the refugees worldwide are children. There have been
      numerous studies reporting their levels of psychological distress. The aim of
      this paper is to review systematically and synthesize the epidemiological
      research concerning the mental health of refugee children residing in Western
      countries. A Cochrane Collaboration style review was conducted searching nine
      major databases, bibliographies, and grey literature from 2003 to 2008. Included
      studies had to meet the reporting standards of STROBE and investigate mental
      health in non-clinical samples of asylum seeking and refugee children residing in
      OECD countries. A total of twenty-two studies were identified of 4,807 retrieved
      citations, covering 3,003 children from over 40 countries. Studies varied in
      definition and measurement of problems, which included levels of post-traumatic
      stress disorder from 19 to 54%, depression from 3 to 30%, and varying degrees of
      emotional and behavioral problems. Significant factors influencing levels of
      distress appear to include demographic variables, cumulative traumatic pre
      migration experiences, and post-migration stressors. Importantly, the research
      base demands greater contextual and methodological refining such that future
      research would have greater generalizability and clinical implications.

PMID- 21181270
TI  - Inter-ethnic variability of three functional polymorphisms affecting the IMPDH2
      gene.
AB  - Human type II inosine monophosphate dehydrogenase (IMPDH2) is a key enzyme in the
      purine nucleotide biosynthetic pathway and constitutes a pivotal biological
      target for immunosuppressant and antiviral drugs. Several Single Nucleotide
      Polymorphisms (SNP) affecting the IMPDH2 gene sequence have been reported with
      potential functional relevance and could impact drugs response. We aimed to
      determine the frequency of three of these polymorphisms, namely g.3375C>T
      (Leu(263)Phe), c.-95T>G and IVS7+10T>C, in Caucasians, Tunisians, Peruvians and
      Black Africans (Gabonese and Senegalese). The g.3375C>T and c.-95T>G
      polymorphisms are rare with a Minor Allele Frequency <=1.0% in our populations,
      whereas the third variant, IVS7+10T>C, is more frequent and displays large
      interethnic variations, with an allelic frequency ranging from 14.6% in the
      French Caucasian population studied to less than 2% in Black African and Peruvian
      populations. This ethnic-related data might contribute to a better understanding
      of the variability in clinical outcome and/or dose adjustments of drugs that are
      IMPDH inhibitors such as mycophenolic acid.

PMID- 21181271
TI  - Using COI gene sequence to barcode two morphologically alike species: the cotton
      bollworm and the oriental tobacco budworm (Lepidoptera: Noctuidae).
AB  - Due to limited morphological difference, the two closely related sister species,
      the cotton bollworm, Helicoverpa armigera (Hubner) and the oriental tobacco
      budworm, H. assulta (Guenee) (Lepidoptera: Noctuidae), are very difficult to
      distinguish, especially at the larvae stage. Recently, DNA sequence has been
      widely used as a bio-barcode for species identification. In this study, we
      attempted to distinguish H. armigera and H. assulta using the mitochondrial
      cytochrome C oxidase subunit I gene (COI) gene sequence as the barcode. We
      determined a 658 bp segment of the COI gene for 28 individuals of H. armigera, 8
      individuals of H. assulta, and 10 individuals of Mamestra brassicae (as the
      outgroup) in Yunnan Province, southwest of P. R. China, together with one H.
      assulta and two H. armigera reported sequences from GenBank. Twenty-three
      haplotypes were identified in all 49 samples. As expected, network analysis of
      the haplotypes of the three species presented a clustering pattern consistent
      with the respective species status. Haplotypes of the same species differed from
      each other by no more than three nucleotide substitutions. However, each
      haplotype of H. armigera differed from that of H. assulta by at least 22
      nucleotide substitutions. Both species differed from M. brassicae by more than 50
      nucleotide substitutions. 17 unique diagnostic nucleotides were also used to
      discriminate the two species. The finding of large COI sequence differences
      between H. armigera and H. assulta suggested that it could be used to distinguish
      the two morphologically alike species and be employed for quick species
      identification during pest control.

PMID- 21181272
TI  - Histonedeacetylase inhibitor Oxamflatin increase HIV-1 transcription by inducing
      histone modification in latently infected cells.
AB  - HIV-1 latency represents a major problem in the eradication of HIV-1 in infected
      individuals treated with highly active anti-retroviral therapy. Histone
      deacetylase (HDAC) inhibits HIV-1 gene expression and virus production and may
      contribute to quiescence of HIV-1 within resting CD4+ T cells. Here, we evaluated
      the effect of Oxamflatin, a class I HDAC inhibitor, on the epigenetic change at
      HIV-1 long terminal repeat (LTR) and the induction of the latent viruses in the
      latency Jurkat T cell line. Flow cytometry assay showed that Oxamflatin activate
      HIV-1 gene expression in these latently infected cells by 2-17 fold than
      background levels. Chromatin immunoprecipitation (ChIP) assays further revealed
      that Oxamflatin increase the acetylation level of histone H3 and histone H4 at
      the nucleosome 1(nuc-1) site of the HIV-1 LTR compared to mock treatment. We also
      found that Oxamflatin had a synergization with prostratin, or 5-azacytidine or
      tumor necrosis factor-alpha to activate the HIV-1 promoter. Taken together, our
      results suggest that the histone acetylation plays an important role in
      regulating HIV-1 LTR gene expression, and Oxamflatin has potential as drug
      candidates as antilatency therapies.

PMID- 21181273
TI  - Proteomic response of barley leaves to salinity.
AB  - Drought and salinity stresses are adverse environmental factors that affect crop
      growth and yield. Proteomic analysis offers a new approach to identify a broad
      spectrum of genes that are expressed in living system. We applied this technique
      to investigate protein changes that were induced by salinity in barley genotypes
      (Hordeum vulgare L.), Afzal, as a salt-tolerant genotype and L-527, as a salt
      sensitive genotype. The seeds of two genotypes were sown in pot under controlled
      condition of greenhouse, using a factorial experiment based on a randomized
      complete block design with three replications. Salt stress was imposed at
      seedling stage and leaves were collected from control and salt-stressed plant.
      The Na(+) and K(+) concentrations in leaves changed significantly in response to
      short-term stress. About 850 spots were reproducibly detected and analyzed on 2
      DE gels. Of these, 117 proteins showed significant change under salinity
      condition in at least one of the genotypes. Mass spectrometry analysis using
      MALDI-TOF/TOF led to the identification some proteins involved in several salt
      responsive mechanisms which may increase plant adaptation to salt stress
      including higher constitutive expression level and upregulation of antioxidant,
      upregulation of protein involved in signal transduction, protein biosynthesis,
      ATP generation and photosynthesis. These findings may enhance our understanding
      of plant molecular response to salinity.

PMID- 21181274
TI  - Inducible expression of calreticulin-N58 in Pichia pastoris by high density cell
      culture.
AB  - Calreticulin-N58 (CRT-N58), an active fragment of calreticulin with anti
      angiogenesis activity, was expressed in P. pastoris by high density cell culture.
      Calreticulin-N58 DNA was synthesized by PCR and cloned to plasmid pPIC9 K
      resulting in the plasmid pPIC9 K-crt-N58 which was then transformed into P.
      pastoris GS115. The fermentation was carried out in a 50 l bioreactor with 20 l
      modified growth medium recommended by Invitrogen at 30 degrees C. The cells were
      first grown in glycerol-PTM4 trace salts for 24 h. When the cell density was
      grown to A(600) = 135, methanol-PTM4 trace salts was added to induce the
      expression of calreticulin-N58. During the fermentation, dissolved oxygen level
      was maintained at 20-30%, pH was controlled at 5 by adding 7 M NH(4)OH. After 52
      h of induction, the yield of secreted calreticulin-N58 was 70 mg/l and biomass
      growth was 293 as measured by absorption of 600 nm. The secreted calreticulin-N58
      was purified to a purity of 100% by the use of SP-Sepharose FF ion-exchange
      chromatography (Pharmacia Biotech. NJ, USA) and desalted with ultrafiltration
      device (Millipore, Bedford, MA, USA). The recombinant calreticulin-N58 induced
      endothelial cell apoptosis and inhibited the angiogenesis on the CAM.

PMID- 21181276
TI  - Prevalence of HBV genotypes among Egyptian hepatitis patients.
AB  - Phylogenetic analysis has led to the classification of hepatitis B virus into
      eight genotypes, designated A to H. The genotypes have differences in biological
      properties and show heterogeneity in their global distribution. These attributes
      of the genotypes may account not only for differences in the prevalence of
      hepatitis B virus mutants in various geographic regions, but also makes them
      responsible for differences in the clinical outcome and response to antiviral
      treatment in different population groups. Africa is one of the highly endemic
      regions of HBV with five genotypes (A-E) identified. Almost all patients in the
      Mediterranean area are infected with genotype D. However, there is little
      information of genotype distribution in Egypt. A total of 140 Egyptian patients
      with hepatitis B surface antigen (HBsAg) positive were enrolled in this study. Of
      the 140 patients, only 100 patients were HBV DNA positive and only these were
      included in the study. They were classified into 20 patients with acute hepatitis
      (AH), 75 patients with chronic active hepatitis (CAH) and 5 patients with
      hepatocellular carcinoma (HCC). HBV genotypes were determined using INNO-LiPA
      methodology which is based on the reversed hybridization principle. This study
      showed that genotype D constituted 87% of the total infections (75 CAH cases, 7
      AH cases and 5 HCC cases). The other 13% showed mixed infections of D/F. These
      findings show that the most prevalent genotype in Egypt is genotype D especially
      in CAH and HCC patients while the mixed type D/F is only encountered in AH.

PMID- 21181275
TI  - Association study of single nucleotide polymorphisms in pre-miRNA and rheumatoid
      arthritis in a Han Chinese population.
AB  - The aim of this study was to perform an association study between two single
      nucleotide polymorphisms (SNPs) rs2910164 G>C and rs3746444 T>C in pre-miRNA (hsa
      mir-146a and hsa-mir-499) and rheumatoid arthritis (RA) in the Han Chinese
      population. 208 Han Chinese patients with RA and 240 healthy controls were
      recruited in this study. The SNPs was genotyped by polymerase chain reaction
      restriction fragment length polymorphism. Anti-cyclic citrullinated peptide (anti
      CCP) antibody was measured by enzyme linked immunosorbent assay and rheumatoid
      factor (RF) was measured by rate nephelometry. The genotype frequencies between
      cases and controls were compared by chi(2) analysis. No significant association
      between the SNPs (rs2910164 and rs3746444) and RA was observed (P = 0.631 and
      0.775, respectively), and the SNPs did not show any association with the RF
      positive (P = 0.631 and 0.775, respectively). However, there was a significant
      difference on the level of anti-CCP antibody between different genotypes in
      rs3746444 (P = 0.007). The heterozygote CT had significantly higher level of anti
      CCP antibody compared with homozygote CC and TT (P = 0.054 and 0.003,
      respectively). We first investigated the association between the SNPs (rs2910164
      G>C and rs3746444 T>C) in the pre-miRNA (hsa-mir-146a and hsa-mir-499) and RA in
      a Han Chinese population. We did not find a significant association between the
      SNPs and the susceptibility to RA, while the SNP rs3746444 may affect anti-CCP
      antibody production.

PMID- 21181277
TI  - Intrapituitary cytokines in Cushing's disease: do they play a role?
AB  - A large body of in vitro evidence shows that cytokines influence the hypothalamic
      pituitary-adrenal axis both in physiological conditions and in Cushing's disease
      (CD). In order to study in vivo the role of intrapituitary cytokines in CD, we
      assayed two cytokines known for their action on the pituitary, i.e. interleukin-1
      beta (IL-1beta) and interleukin-6 (IL-6), and also soluble interleukin-6 receptor
      (sIL-6R), important for the neural activities of IL-6, in a carefully selected
      sample of subjects affected by CD undergoing bilateral inferior petrosal sinus
      sampling. Similarly to ACTH, all cytokines basally showed a higher concentration
      in the ipsilateral sinus compared to the controlateral one and to that of
      peripheral blood; after CRH infusion, both ipsilaterally and controlaterally, IL
      6 and sIL-6R values increased compared to basal ones, while IL-1beta increased
      significantly up to 5 min after CRH and then decreased significantly compared to
      basal values in subsequent measurements; peripherically no significant variations
      in the cytokines were observed after CRH. Again similarly to ACTH, the three
      cytokines presented a higher increase ipsilaterally than controlaterally;
      moreover all three interleukins in the ipsilateral sinuses showed positive and
      significant correlations between their basal value and that of basal ACTH. These
      findings allow us to hypothesize that the central production of IL-1beta and IL-6
      could be involved in ACTH hypersecretion which occurs in CD: more specifically,
      we hypothesize that these cytokines are produced directly by the corticotroph
      adenoma and have the task of enhancing tumoral secretion of ACTH with an
      autocrine-paracrine mechanism.

PMID- 21181278
TI  - Endoscopic endonasal approach for pituitary adenoma: surgical complications in
      301 patients.
AB  - The authors investigate the complications of transnasal transsphenoidal
      endoscopic surgery in the treatment of 301 patients with pituitary adenomas. A
      retrospective analysis of complications in 301 patients submitted to
      transsphenoidal transnasal endoscopic surgery at the General Hospital of
      Fortaleza, Brazil between January 1998 and December 2009. The complications were
      divided in two groups: anatomical (oronasofacial, sphenoid sinus, intrasellar,
      suprasellar and parasellar) and endocrinological complications (anterior and
      posterior pituitary dysfunctions). We observed a total of 81 complications
      (26.9%) in our series. Anatomical complications occurred in 8.97% (27 cases): 8
      CSF postoperative leaks (2.6%), 6 cases (1.9%) of delayed nasal bleeding, 5 cases
      (1.6%) of sphenoidal sinusitis, 3 cases (0.9%) of carotid artery lesion, 2 cases
      of meningitis (0.6%) and one case (0.3%) of each of the uncommon following
      complications: intrasella-suprasella hematoma, pontine hematoma and chiasmaplexy.
      Endocrinological complications occurred in 17.9% (54 cases): additional
      postoperative anterior lobe insufficiency in 35 cases (11.6%), and postoperative
      diabetes insipidus in 19 cases (6.3%). In our series, 3 cases of deaths (not
      directly related to the procedure) were also observed. Endoscopic transsphenoidal
      surgery represents an effective option for the treatment of patients with
      pituitary tumor. Complications still occur and must be reduced as much as
      possible. Successful endoscopic pituitary surgery requires extensive training in
      the use of an endoscope and careful planning of the surgery. Additional
      improvement can be expected with greater experience and new technical
      developments.

PMID- 21181280
TI  - Continuous occlusion of hepatic artery proper for prevention of blood loss in
      partial hepatectomy for ruptured hepatocellular carcinoma: a case-matched
      comparative study.
AB  - BACKGROUND: To investigate the efficacy and safety of adding continuous occlusion
      of hepatic artery proper to intermittent Pringle maneuver in partial hepatectomy
      for ruptured hepatocellular carcinoma. MATERIALS AND METHODS: This is a
      retrospective study on data that were prospectively collected and entered into a
      computer database. A total of 36 patients who underwent partial hepatectomy for
      ruptured HCC by adding continuous occlusion of hepatic artery proper to
      intermittent Pringle maneuver at a tertiary care university hospital were
      compared with a historical case-matched control group of 36 patients who received
      intermittent Pringle maneuver only. RESULTS: The patient characteristics were
      comparable for the 2 groups of patients. The mean hepatic artery occlusion time
      was 58 min (range 36-98 min). Intraoperative blood loss and blood transfusion
      rate in the study group were significantly lower than the control group (P < .001
      and P = .004, respectively). There were no significant differences in the
      postoperative serum aspartate transaminase and total bilirubin levels (P = .087,
      P = .135, respectively), and in the postoperative hospital stay and surgical
      complications according to Clavien's classification between the two groups (P =
      0.213, P = 1.000, respectively). The disease-free survival rates in the study
      group was significantly better than the control group (P = .023). Overall, HCC
      patients with rupture had poor prognosis. CONCLUSIONS: The addition of continuous
      occlusion of hepatic artery proper to intermittent Pringle maneuver significantly
      reduced intraoperative blood loss for partial hepatectomy in patients with
      ruptured HCC when compared with intermittent Pringle maneuver alone. The
      procedure was found to be safe even for patients with liver cirrhosis.

PMID- 21181281
TI  - Lower uterine segment involvement is associated with poor outcomes in early-stage
      endometrioid endometrial carcinoma.
AB  - BACKGROUND: The clinicopathologic significance of lower uterine segment
      involvement (LUSI) in endometrial cancer patients remains unclear. Although LUSI
      has been reported to be a prognostic indicator, literature is limited. METHODS:
      We studied 481 surgically staged endometrioid endometrial cancers with disease
      confined to the uterus (FIGO 1988 stage I or II). Primary outcomes were overall
      survival (OS) and disease-free survival (DFS). The relationships between LUSI and
      OS and DFS were assessed using the Kaplan-Meier method and Cox proportional
      hazard models. The t test or Fisher exact test was used for evaluating
      relationships between variables of interest. RESULTS: LUSI was present in 223
      cases (46.4%), and was associated with both decreased disease free survival (P =
      0.02) and overall survival (P = 0.01) in univariate analysis. Multivariate
      analysis confirmed the association between LUSI and increased risk for recurrence
      [hazard ratio (HR) 2.27; 95% confidence interval (95% CI) 1.09-4.7; P = 0.03] and
      increased mortality (HR 1.76; 95% CI 1.12-2.78; P = 0.01). CONCLUSIONS: LUSI in
      patients with early-stage endometrioid endometrial cancer is associated with
      decreased survival.

PMID- 21181282
TI  - Tight binding of proteins to membranes from older human cells.
AB  - The lens is an ideal model system for the study of macromolecular aging and its
      consequences for cellular function, since there is no turnover of lens fibre
      cells. To examine biochemical processes that take place in the lens and that may
      also occur in other long-lived cells, membranes were isolated from defined
      regions of human lenses that are synthesised at different times during life, and
      assayed for the presence of tightly bound cytosolic proteins using quantitative
      iTRAQ proteomics technology. A majority of lens beta crystallins and all gamma
      crystallins became increasingly membrane bound with age, however, the chaperone
      proteins alpha A and alpha B crystallin, as well as the thermally-stable protein,
      betaB2 crystallin, did not. Other proteins such as brain-associated signal
      protein 1 and paralemmin 1 became less tightly bound in the older regions of the
      lens. It is evident that protein-membrane interactions change significantly with
      age. Selected proteins that were formerly cytosolic become increasingly tightly
      bound to cell membranes with age and are not removed even by treatment with 7 M
      urea. It is likely that such processes reflect polypeptide denaturation over time
      and the untoward binding of proteins to membranes may alter membrane properties
      and contribute to impairment of communication between older cells.

PMID- 21181283
TI  - [Drug therapy of patients with recurrent glioblastoma: is there any evidence?].
AB  - SYSTEMIC THERAPY IN PATIENTS WITH RELAPSED GLIOBLASTOMA: For patients with
      relapsed GBM there is currently no standard systemic therapy. TEMOZOLOMIDE
      RECHALLENGE: Wick et al. treated 64 patients with TMZ 150 mg/m(2), one week on,
      one week off and observed PFS-6 of 43.8%, and OAS of 8.4 months after the
      diagnosis of relapse. Strik et al. reported on 13 patients treated 5 days in a
      week and observed a PFS-6 of 39%, OAS of 7.8 months, Perry et al. reported on 50
      mg/m(2). BEVACIZUMAB: Vredenburgh et al. reported prospectively rapid symptomatic
      relief, PFS-6 of 46% and OAS of 8 months in 35 patients with relapsed GBM. The
      BRAIN study evaluated 167 patients with Avastin/Irinotecan vs. Avastin alone in
      patients with relapsed GBM, showing PFS-6 of 50 vs. 42% and OAS of 8.7 vs. 9.2
      months. EXPERIMENTAL TREATMENT: More than 40 drugs are currently investigated in
      patients with relapsed gliomas. BEST SUPPORTIVE CARE: Should be part of all
      interactions with a neuro-oncologist. CONCLUSIONS: Thorough consideration of the
      individual patient's characteristics to evaluate the best fitted treatment is
      warranted, preferentially in the context of an interdisciplinary tumour board.

PMID- 21181284
TI  - Five condensed furanocoumarins from the root of Heracleum candicans Wall.
AB  - Three new spirotrifuranocoumarins, canditririns C-E (1-3), a new
      spirotetrafuranocoumarin, canditetrarin A (4), and a new tetrafuranocoumarin,
      canditetrarin B (5), were isolated from the roots of Heracleum candicans Wall.
      Their structures were established using spectral methods.

PMID- 21181285
TI  - Aerobic training in rats increases skeletal muscle sphingomyelinase and serine
      palmitoyltransferase activity, while decreasing ceramidase activity.
AB  - Sphingolipids are important components of cell membranes that may also serve as
      cell signaling molecules; ceramide plays a central role in sphingolipid
      metabolism. The aim of this study was to examine the effect of 5 weeks of aerobic
      training on key enzymes and intermediates of ceramide metabolism in skeletal
      muscles. The experiments were carried out on rats divided into two groups: (1)
      sedentary and (2) trained for 5 weeks (on a treadmill). The activity of serine
      palmitoyltransferase (SPT), neutral and acid sphingomyelinase (nSMase and
      aSMase), neutral and alkaline ceramidases (nCDase and alCDase) and the content of
      sphingolipids was determined in three types of skeletal muscle. We also measured
      the fasting plasma insulin and glucose concentration for calculating HOMA-IR
      (homeostasis model assessment) for estimating insulin resistance. We found that
      the activities of aSMase and SPT increase in muscle in the trained group. These
      changes were followed by elevation in the content of sphinganine. The activities
      of both isoforms of ceramidase were reduced in muscle in the trained group.
      Although the activities of SPT and SMases increased and the activity of CDases
      decreased, the ceramide content did not change in any of the studied muscle.
      Although ceramide level did not change, we noticed increased insulin sensitivity
      in trained animals. It is concluded that training affects the activity of key
      enzymes of ceramide metabolism but also activates other metabolic pathways which
      affect ceramide metabolism in skeletal muscles.

PMID- 21181286
TI  - COX-2 inhibition and inhibition of cytosolic phospholipase A2 increase CD36
      expression and foam cell formation in THP-1 cells.
AB  - Cardiovascular safety of cyclooxygenase (COX)-2-selective inhibitors and
      nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) is of worldwide
      concern. COX-2 inhibitors and NSAIDs act by inhibiting arachidonic acid
      metabolism to prostaglandins. They confer a cardiovascular hazard manifested as
      an elevated risk of myocardial infarction. Mechanisms underlying these
      cardiovascular effects are uncertain. Here we determine whether interference with
      cytosolic phospholipase A2 (cPLA-2) or COX-2 through pharmacologic blockade or
      silencing RNA impacts expression of scavenger receptor CD36 and scavenger
      receptor A, both involved in cholesterol uptake in monocytes and macrophages. THP
      1 human monocytes and human peripheral blood mononuclear cells were exposed to
      celecoxib, a COX-2 selective inhibitor currently in clinical use, and to
      arachidonyl trifluoromethyl ketone (AACOCF3), an arachidonic acid analog that
      selectively inhibits cPLA-2. Celecoxib and AACOCF3 each upregulated expression of
      CD36, but not scavenger receptor A, as determined by quantitative PCR and
      immunoblotting. Silencing of cPLA-2 or COX-2 had comparable effects to
      pharmacologic treatments. Oil red O staining revealed a profound increase in foam
      cell transformation of THP-1 macrophages exposed to either celecoxib or AACOCF3
      (both 25 MUM), supporting a role for the COX pathway in maintaining macrophage
      cholesterol homeostasis. Demonstration of disrupted cholesterol balance by
      AACOCF3 and celecoxib provides further evidence of the possible mechanism by
      which COX inhibition may promote lipid overload leading to atheromatous lesion
      formation and increased cardiovascular events.

PMID- 21181287
TI  - The impact of health plan physician-tiering on access to care.
AB  - BACKGROUND: In an attempt to improve quality and control costs, health plans are
      creating tiered products that encourage enrollees to seek care from "high-value"
      physicians. However, tiered products may limit access to care because patients
      may have to travel unreasonable distances to visit the nearest high-value
      physician. OBJECTIVE: To assess geographic access to high-value physicians,
      particularly for disadvantaged populations. DESIGN: Cross-sectional observational
      study. PARTICIPANTS: Physicians and adult patients in Massachusetts. MAIN
      MEASURES: Travel time from census block centroid to nearest physician address
      under two scenarios: patients can see (1) any physician or (2) only high-value
      physicians. KEY RESULTS: Among the physicians, 768 (20.9%) primary care
      physicians (PCPs), 225 (26.6%) obstetricians/gynecologists, 69 (10.3%)
      cardiologists, and 31 (6.0%) general surgeons met the definition of high-value.
      Statewide mean travel times to the nearest PCP, obstetrician/gynecologist,
      cardiologist, or general surgeon under the two scenarios (any physician vs. only
      high-value physicians) were 2.8 vs. 4.8, 6.0 vs. 7.2, 7.0 vs. 12.4, and 6.6 vs.
      14.8 minutes, respectively. Across the four specialties, between 89.4%-99.4% of
      the population lived within 30 minutes of the nearest high-value physician. Rural
      populations had considerably longer travel times to see high-value physicians,
      but other disadvantaged populations generally had shorter travel times than
      comparison groups. CONCLUSIONS: Most patients in Massachusetts are likely to have
      reasonable geographic access to high-value physicians in tiered health plans.
      However, local demographics, especially rural residence, should be taken into
      consideration when applying tiered health plans broadly. Future work should
      investigate whether patients can and will switch to receive care from high-value
      physicians.

PMID- 21181289
TI  - Control of health care-associated infections.

PMID- 21181291
TI  - Preoperative 4-week low-calorie diet reduces liver volume and intrahepatic fat,
      and facilitates laparoscopic gastric bypass in morbidly obese.
AB  - BACKGROUND: The aim of this study was to explore changes in liver volume and
      intrahepatic fat in morbidly obese patients during 4 weeks of low-calorie diet
      (LCD) before surgery and to investigate if these changes would facilitate the
      following laparoscopic gastric bypass. METHODS: Fifteen female patients (121.3
      kg, BMI 42.9) were treated preoperatively in an open study with LCD (800-1,100
      kcal/day) during 4 weeks. Liver volume and fat content were assessed by magnetic
      resonance imaging and spectroscopy before and after the LCD treatment. RESULTS:
      Liver appearance and the complexity of the surgery were scored at the operation.
      Eighteen control patients (114.4 kg, BMI 40.8), without LCD were scored
      similarly. Average weight loss in the LCD group was 7.5 kg, giving a mean weight
      of 113.9 kg at surgery. Liver volume decreased by 12% (p < 0.001) and
      intrahepatic fat by 40% (p < 0.001). According to the preoperative scoring, the
      size of the left liver lobe, sharpness of the liver edge, and exposure of the
      hiatal region were improved in the LCD group compared to the controls (all p <
      0.05). CONCLUSIONS: The overall complexity of the surgery was perceived lower in
      the LCD group (p < 0.05), due to improved exposure and reduced psychological
      stress (both p < 0.05). Four weeks of preoperative LCD resulted in a significant
      decrease in liver volume and intrahepatic fat content, and facilitated the
      subsequent laparoscopic gastric bypass as scored by the surgeon.

PMID- 21181290
TI  - Routine abdominal drains after laparoscopic sleeve gastrectomy: a retrospective
      review of 353 patients.
AB  - Complications after laparoscopic sleeve gastrectomy (LSG) are usually silent and
      difficult to interpret. Our purpose was to evaluate the utility of routine
      placement of intraperitoneal drains at the end of LSG in detection and management
      of postoperative complications. This is a retrospective study of all patients
      that underwent LSG by a standard operative team in a 3-year period. Patients were
      enrolled in Group A when an intraperitoneal drain was placed and Group B when
      not. Three hundred and fifty-three patients underwent LSG with a median
      preoperative BMI of 46.4 k/m2. Two hundred and one patients were enrolled in
      group A and 152 in group B; the two groups were comparable in their
      characteristics. Staple line leak, bleeding, and abscess were observed in 4%,
      2.9%, and 2.5% of group A and 2.6%, 1.9%, and 1.9% of group B and the differences
      did not reach statistical significance. In 50% of patients with drain and leak,
      per os blue de methylene test was negative and in another 50% leak took place
      after the fourth postoperative day when drain was already taken off. Abscesses
      were observed significantly more often in patients that had suffered
      postoperative bleeding (p < 0.001) or had undergone laparoscopic adjustable
      gastric banding (LAGB) in the past (p = 0.02). Placement of drains does not
      facilitate detection of leak, abscess, or bleeding. Furthermore, they don't seem
      to eliminate the reoperation rates for these complications. Maybe patients with
      previous LAGB and intraperitoneal bleeding could benefit from placement of a
      drain that will remain for more than 5 days.

PMID- 21181292
TI  - Chemical form of selenium affects its uptake, transport, and glutathione
      peroxidase activity in the human intestinal Caco-2 cell model.
AB  - Determining the effect of selenium (Se) chemical form on uptake, transport, and
      glutathione peroxidase activity in human intestinal cells is critical to assess
      Se bioavailability at nutritional doses. In this study, we found that two sources
      of L-selenomethionine (SeMet) and Se-enriched yeast each increased intracellular
      Se content more effectively than selenite or methylselenocysteine (SeMSC) in the
      human intestinal Caco-2 cell model. Interestingly, SeMSC, SeMet, and digested Se
      enriched yeast were transported at comparable efficacy from the apical to
      basolateral sides, each being about 3-fold that of selenite. In addition, these
      forms of Se, whether before or after traversing from apical side to basolateral
      side, did not change the potential to support glutathione peroxidase (GPx)
      activity. Although selenoprotein P has been postulated to be a key Se transport
      protein, its intracellular expression did not differ when selenite, SeMSC, SeMet,
      or digested Se-enriched yeast was added to serum-contained media. Taken together,
      our data show, for the first time, that the chemical form of Se at nutritional
      doses can affect the absorptive (apical to basolateral side) efficacy and
      retention of Se by intestinal cells; but that, these effects are not directly
      correlated to the potential to support GPx activity.

PMID- 21181293
TI  - Adipocyte hypoxia increases hepatocyte hepcidin expression.
AB  - Hepcidin plays a key role in regulating iron metabolism by blocking iron efflux
      from macrophages and enterocytes. Hepcidin is synthesized primarily in the liver,
      and its expression is increased by iron overload and inflammation. Obesity is
      associated with chronic inflammation as well as poor iron status. Central obesity
      causes adipocyte hypoxia resulting in chronic inflammation. Therefore, the
      objective of the present study was to determine if adipocyte hypoxia and
      associated inflammation signal hepatocyte hepcidin expression. The effect of
      adipocyte hypoxia on hepcidin expression was modeled using a 3T3-L1
      adipocyte/Huh7 hepatocyte co-culture model. Adipocytes were cultured at either
      standard conditions (19% O2) or hypoxic conditions (1% O2). Compared to standard
      conditions, hypoxic 3T3-L1 cells had significantly higher IL-6 and leptin
      expression. Treatment of Huh7 cells with media from hypoxic or LPS-treated 3T3-L1
      adipocytes significantly increased hepcidin promoter activity and mRNA compared
      to cells treated with normoxic 3T3-L1 media or control media. When the hepcidin
      STAT3 binding site was mutated, promoter activation by hypoxic media was
      abrogated. These data suggest that adipocyte hypoxia (a feature of central
      obesity) may increase hepcidin expression and plays a role in the association
      between obesity and poor iron status.

PMID- 21181298
TI  - The gamma-secretase modulator CHF5074 reduces the accumulation of native
      hyperphosphorylated tau in a transgenic mouse model of Alzheimer's disease.
AB  - The relationship between beta-amyloid (Abeta) and tau is not fully understood,
      though it is proposed that in the pathogenesis of Alzheimer's disease (AD) Abeta
      accumulation precedes and promotes tau hyperphosphorylation via activation of
      glycogen synthase kinase-3beta (GSK-3beta). Both events contribute to learning
      and memory impairments. Modulation of gamma-secretase activity has proved to
      reduce the Abeta burden and cognitive deficits in mouse models of AD, but its
      ability in reducing the tau pathology remains elusive. Chronic treatments with
      two gamma-secretase modulators, ibuprofen and CHF5074, disclosed higher activity
      of CHF5074 in ameliorating brain plaque deposition and spatial memory deficits in
      transgenic mice expressing human amyloid precursor protein (hAPP) with Swedish
      and London mutations (APP(SL) mice). The aim of our study was to investigate in
      APP(SL) mice the effect of the two compounds on the accumulation of native
      hyperphosphorylated tau as well as on the GSK-3beta signaling. CHF5074 was more
      effective than ibuprofen in reducing tau pathology, though both compounds
      decreased the GSK-3beta level and increased the GSK-3beta inhibitory
      phosphorylation near to the non-Tg values. The inhibition of GSK-3beta appeared
      to be secondary to the reduction of Abeta generation as, differently from LiCl,
      CHF5074 reproduced its effect in hAPP-overexpressing neuroglioma cells, but not
      in wild-type primary neurons. Our data show that the novel gamma-secretase
      modulator CHF5074 can fully reverse beta-amyloid-associated tau pathology, thus
      representing a promising therapeutic agent for AD.

PMID- 21181299
TI  - Critical thresholds for transcranial Doppler indices of cerebral autoregulation
      in traumatic brain injury.
AB  - BACKGROUND: Transcranial Doppler-derived indices of cerebral autoregulation are
      related to outcome after TBI. We analyzed our retrospective material to identify
      thresholds discriminative of outcome for these indices. METHODS: 248 sedated and
      ventilated patients after head injury were eligible for the study. The indices of
      autoregulation derived from transcranial Doppler were calculated as correlation
      coefficients of blood flow velocity with cerebral perfusion pressure (index Mx)
      or arterial blood pressure (index Mxa). 2 * 2 tables were created grouping
      patients according to survival-death or favorable-unfavorable outcomes and
      varying thresholds for Mx and Mxa. Pearson's chi-square was calculated.
      Thresholds returning the highest chi-square value were assumed to have the best
      discriminative value between survival-death and favorable-unfavorable outcomes.
      RESULTS: Mx and Mxa demonstrated that worse autoregulation is associated with
      poorer outcome and greater mortality (P = 0.0033 for Mx and P = 0.047 for Mxa).
      Both indices were more effective for prediction of favorable outcome than
      mortality. Chi-square for Mx showed a double peak with thresholds at 0.05 and
      0.3. Mxa had only one peak at 0.3. Peak chi-square for Mx (11.3) was greater than
      for Mxa (8.7), indicating that Mx was a better discriminant of outcome than Mxa.
      CONCLUSIONS: We propose that Mx greater than 0.3 indicates definitely disturbed
      autoregulation and lower than 0.05 good autoregulation. For values between 0.05
      and 0.3 the state of autoregulation is uncertain.

PMID- 21181300
TI  - Rare pediatric adrenocortical carcinoma with oncocytic change: a cytologic
      dilemma.
AB  - Pediatric adrenocortical carcinoma is extremely rare with a prevalence of 0.3 per
      million. Adrenocortical neoplasms in children usually present with one of the
      endocrine abnormalities. Adrenocortical neoplasms cannot be easily diagnosed on
      cytopathology; hence, the cytomorphological features posing diagnostic dilemmas
      are discussed in a pediatric patient presenting with palpable abdominal mass and
      virilization. Fine-needle aspiration smears were cellular showing cells in
      cohesive clusters adhering to central core of capillaries exhibiting an endocrine
      vascular pattern along with single cells and stripped nuclei. Cells were
      polygonal in shape and had abundant cytoplasm with well-defined borders and round
      eccentric nuclei with prominent nucleoli. Marked anisonucleosis was also noted.
      Few cells showed abundant granular cytoplasm resembling oncocytes. Many bizarre
      and multinucleated cells, few mitotic figures, and necrosis were also seen.
      Hematoxylin and eosin-stained sections of tumor biopsy suggested possibility of
      adrenocortical neoplasm. A panel of immunohistochemical markers were used to
      exclude possibility of renal cell carcinoma (RCC) and pheochromocytoma that
      showed vimentin (+), cytokeratin (-), inhibin-alpha (+), neuron-specific enolase
      (focally +), and chromogranin (-). The Ki67 index was 15%, and P53 was strongly
      positive. It is difficult to distinguish adrenocortical neoplasm, RCC, and
      pheochromocytoma on cytology because of overlapping features; hence, important
      cytological features which help in distinguishing between the three are
      discussed.

PMID- 21181301
TI  - Innate immunity in atopic dermatitis.
AB  - Atopic dermatitis (AD) is a clinically defined, highly pruritic, chronic
      inflammatory skin disease. In AD patients, the combination of a genetic
      predisposition for skin barrier dysfunction and dysfunctional innate and adaptive
      immune responses leads to a higher frequency of bacterial and viral skin
      infections. The innate immune system quickly mobilizes an unspecific,
      standardized first-line defense against different pathogens. Defects in this
      system lead to barrier dysfunction which results in increased protein allergen
      penetration through the epidermis and predisposes to secondary skin infections.
      Two loss-of-function mutations in the epidermal filaggrin gene are associated
      with AD. Also, inducible endogenous antibiotics such as the antimicrobial
      peptides cathelicidin and the beta-defensins may show defective function in
      lesional AD skin. Eczema herpeticum is a disseminated viral infection almost
      exclusively diagnosed in AD patients, which is based on unmasking of the viral
      entry receptor nectin-1, lack of cathelicidin production by keratinocytes, and
      depletion of Type I IFN-producing plasmacytoid dendritic cells from AD skin.
      Future therapeutic approaches to AD may include enhancement of impaired innate in
      addition to downregulation of dysfunctional adaptive immunity.

PMID- 21181302
TI  - Role of dendritic cells in atopic dermatitis: an update.
AB  - Dendritic cells (DCs) have been recognized as key players bridging innate and
      adaptive immune systems. They control the balance of the adaptive immune
      response, and the functional behavior of DCs is mainly dictated by their
      microenvironment. Atopic dermatitis (AD) is a paradigmatic disease where the
      inflammatory microenvironment has a deep impact on DCs. The emergence of IgE
      mediated sensitization is tightly related to the impact of locally released
      cytokines by either keratinocytes, T cells, or other cells involved in the
      inflammatory reaction. This review will focus on the recent and relevant findings
      in the field of immunobiology of DCs and their role in AD.

PMID- 21181303
TI  - Cutting-edge issues in celiac disease and in gluten intolerance.
AB  - Celiac disease (CD) is a gluten-dependent immune-mediated disease with a
      prevalence in the general population estimated between 0.3% and 1.2%. Large-scale
      epidemiological studies have shown that only 10-20% of cases of CD are identified
      on the basis of clinical findings and that laboratory tests are crucial to
      identify subjects with subtle or atypical symptoms. The correct choice and
      clinical use of these diagnostic tools may enable accurate diagnosis and early
      recognition of silent CD cases. In this review, we have considered some relevant
      aspects related to the laboratory diagnosis of CD and, more extensively, of
      gluten intolerance, such as the best combination of tests for early and accurate
      diagnosis, the diagnostic role of new tests for detecting antibodies against
      neoepitopes produced by the transglutaminase-gliadin complex, the forms of non
      celiac gluten intolerance (gluten sensitivity), and the use and significance of
      measuring cytokines in CD.

PMID- 21181304
TI  - Viruses and cytotoxic T lymphocytes in type 1 diabetes.
AB  - Histopathological studies on pancreas tissues from individuals with recent-onset
      type 1 diabetes (T1D) consistently find that CD8 T cells substantially contribute
      to the formation of islet lesions. CD8 T cells reactive against islet-associated
      antigens can also be found in blood samples from T1D patients. Mechanistic
      studies on the pathogenic role of this T cell subset have mostly focused on two
      animal models, i.e., the non-obese diabetic mouse and the virally induced rat
      insulin promoter-lymphocytic choriomeningitis virus model. Data were obtained in
      support of a role for viral infection in expanding a population of diabetogenic
      cytotoxic T lymphocytes. In view of the theorized association of viral infection
      with initiation of islet autoimmunity and progression to clinically overt
      disease, CD8 T cells thus represent an attractive target for immunotherapy. We
      will review here arguments in favor of a pivotal role for CD8 T cells in driving
      T1D development and speculate on etiologic agents that may provoke their aberrant
      activation.

PMID- 21181305
TI  - SynapticDB, effective web-based management and sharing of data from serial
      section electron microscopy.
AB  - Serial section electron microscopy (ssEM) is rapidly expanding as a primary tool
      to investigate synaptic circuitry and plasticity. The ultrastructural images
      collected through ssEM are content rich and their comprehensive analysis is
      beyond the capacity of an individual laboratory. Hence, sharing ultrastructural
      data is becoming crucial to visualize, analyze, and discover the structural basis
      of synaptic circuitry and function in the brain. We devised a web-based
      management system called SynapticDB (http://synapses.clm.utexas.edu/synapticdb/)
      that catalogues, extracts, analyzes, and shares experimental data from ssEM. The
      management strategy involves a library with check-in, checkout and experimental
      tracking mechanisms. We developed a series of spreadsheet templates (MS Excel,
      Open Office spreadsheet, etc) that guide users in methods of data collection,
      structural identification, and quantitative analysis through ssEM. SynapticDB
      provides flexible access to complete templates, or to individual columns with
      instructional headers that can be selected to create user-defined templates. New
      templates can also be generated and uploaded. Research progress is tracked via
      experimental note management and dynamic PDF forms that allow new investigators
      to follow standard protocols and experienced researchers to expand the range of
      data collected and shared. The combined use of templates and tracking notes
      ensures that the supporting experimental information is populated into the
      database and associated with the appropriate ssEM images and analyses. We
      anticipate that SynapticDB will serve future meta-analyses towards new
      discoveries about the composition and circuitry of neurons and glia, and new
      understanding about structural plasticity during development, behavior, learning,
      memory, and neuropathology.

PMID- 21181306
TI  - Characterization of a novel umbilical cord lining cell with CD227 positivity and
      unique pattern of P63 expression and function.
AB  - Umbilical cord tissue is gaining attention as a novel source of multipotent stem
      cells because it is easily obtainable, ethically acceptable and the cells are
      immunologically naive. In this study, we have isolated and characterized a new
      cell type expressing MUCIN1 (CD227) from human umbilical cord lining which we
      termed MUCIN-expressing Cord Lining Epithelial Cell (CLEC-muc). We found that
      CLEC-muc is highly proliferative and had significant clonogenic ability. These
      cells express embryonic stem cell markers OCT-4, NANOG, SSEA-4, REX1 and SOX2.
      Despite the abundant expression of epithelial cell marker MUCIN1 and
      cytokeratins, this population is also positive to the mesenchymal stem cell (MSC)
      marker CD166. CLEC-muc is unique in p63 expression that shuttles from the
      cytoplasm to the nucleus over time in culture. To understand p63 regulation and
      function in CLEC-muc, cells were treated with BMP4, a potent morphogen that plays
      a role in epidermal differentiation via p63 upregulation in ES cell and
      subsequent analyses were done. We found that BMP4 does not alter cytoplasmic
      expression of p63 that promotes cell proliferation. However, it increases nuclear
      p63 expression together with several other epithelial-associated genes such as
      GATA3, JAGGED1, NOTCH1, HES1 and IKKalpha. BMP4 has also been found to weakly
      induce deltaNp63 expression in CLEC-muc. Our results suggest that CLEC-muc is a
      novel stem cell-like population that can be further differentiated by BMP4 to
      generate specific cell-types probably destined to form non-keratinized epithelia.

PMID- 21181307
TI  - Generation of induced pluripotent stem cell lines from Friedreich ataxia
      patients.
AB  - Friedreich ataxia (FRDA) is an autosomal recessive disorder characterised by
      neurodegeneration and cardiomyopathy. It is caused by a trinucleotide (GAA)
      repeat expansion in the first intron of the FXN gene that results in reduced
      synthesis of FXN mRNA and its protein product, frataxin. We report the generation
      of induced pluripotent stem (iPS) cell lines derived from skin fibroblasts from
      two FRDA patients. Each of the patient-derived iPS (FA-iPS) cell lines maintain
      the GAA repeat expansion and the reduced FXN mRNA expression that are
      characteristic of the patient. The FA-iPS cells are pluripotent and form
      teratomas when injected into nude mice. We demonstrate that following in vitro
      differentiation the FA-iPS cells give rise to the two cell types primarily
      affected in FRDA, peripheral neurons and cardiomyocytes. The FA-iPS cell lines
      have the potential to provide valuable models to study the cellular pathology of
      FRDA and to develop high-throughput drug screening assays. We have previously
      demonstrated that stable insertion of a functional human BAC containing the
      intact FXN gene into stem cells results in the expression of frataxin protein in
      differentiated neurons. As such, iPS cell lines derived from FRDA patients,
      following correction of the mutated gene, could provide a useful source of
      immunocompatible cells for transplantation therapy.

PMID- 21181308
TI  - HMGB1 promotes lymphangiogenesis of human lymphatic endothelial cells in vitro.
AB  - High-mobility group box 1 (HMGB1), a proinflammatory cytokine, plays an important
      role in inflammatory diseases, including severe sepsis and arthritis. This recent
      discovery of the extracellular role of HMGB1 as a multifunctional cytokine
      involved in tumorigenesis, tumor angiogenesis as well as metastasis has opened up
      a new field of research to study the role of HMGB1 in tumors. However, its
      molecular mechanism in lymphangiogenesis remains poorly understood. In this
      study, human lymphatic endothelial cells (LECs) were treated with human
      recombinant HMGB1 (rHMGB1) and recombinant VEGF-C (rVEGF-C). Changes in cell
      proliferation, migration, and the capillary-like tube formation were assessed by
      MTT assay, transwell chamber assay, and a Matrigel model, respectively. Human
      rHMGB1 induced LEC proliferation, migration, and tube formation in a dose- and
      time-dependent manner with the maximal effect at a concentration of 2 MUg/ml. As
      a specific lymphangiogenes factor, the role of rVEGF-C in promoting
      lymphangiogenesis was significant. These data indicate, for the first time, that
      HMGB1 might contribute to tumor lymphangiogenesis and lymphatic metastasis, and
      it might ultimately represent a therapeutic target in tumor patients.

PMID- 21181309
TI  - Expression of PTTG1 and PTEN in endometrial carcinoma: correlation with
      tumorigenesis and progression.
AB  - Human pituitary tumor-transforming gene 1 (PTTG1) is a newly identified proto
      oncogene, and its overexpression occurs in a wide variety of human cancers. The
      tumor suppressor gene phosphatase and tensin homolog deleted from chromosome 10
      (PTEN) is frequently mutated or deleted in numerous tumors, especially in
      endometrial carcinoma. The aim of this study was to investigate whether the
      aberrant expression of PTTG1 and PTEN is associated with tumorigenesis and
      progression of endometrial carcinoma. Tissue microarray and immunohistochemical
      staining were undertaken in 124 endometrial carcinoma, 28 atypical hyperplasia
      and 35 normal endometrium samples. Then, the correlation of PTTG1 and PTEN
      expression with the clinicopathological features and with the levels of estrogen
      and progesterone receptor was analyzed. The presence of PTTG1 and PTEN protein
      was significantly increased and decreased, respectively, as lesions progressed
      from normal endometrium to atypical hyperplasia to carcinoma. PTTG1 protein
      showed a significantly positive correlation with TNM stage, but not with other
      characteristics. In addition, PTEN protein did not correlate with any parameters
      except for histological grade, to which it was found to be inversely related.
      Statistical analysis confirmed a significant relationship between an increase in
      PTTG1 and a decrease in PTEN. These results indicate that high expression of
      PTTG1 and low expression of PTEN may be involved in pathogenesis and development
      of endometrial carcinoma. The findings also provide evidence that combined
      evaluation of the two markers may be useful in predicting tumor behavior and thus
      prognosis.

PMID- 21181311
TI  - Origins of and recognition of micronutrient deficiencies after gastric bypass
      surgery.
AB  - Roux-en-Y gastric bypass surgery remains the major surgical option for
      individuals with medically complicated obesity. The importance of preoperative
      evaluation to permit identification of micronutrient deficiencies is being re
      evaluated. The risk of complications related to pregnancy after gastric bypass
      supports careful follow-up. Micronutrient deficiencies are common in
      postoperative gastric bypass patients, despite the suggested use of routine
      vitamin and mineral supplements after surgery. Copper deficiency must be
      considered as an origin for visual disorders after gastric bypass. Vitamin D
      deficiency with metabolic bone disease remains common after gastric bypass and
      the results suggest that the present postoperative supplements of calcium and
      vitamin D are inadequate. Major nutritional complications of bariatric surgery
      are occurring more than 20 years after surgery. There is no evidence for
      intestinal adaptation as there remains decreased intestinal absorption of iron up
      to 18 months after gastric bypass surgery. This article supports ongoing
      examination of nutritional complications after gastric bypass surgery and
      supports the notion that the daily doses of micronutrient supplements, such as
      vitamin D, may need to be revised.

PMID- 21181310
TI  - Approach to dyslipidemia, lipodystrophy, and cardiovascular risk in patients with
      HIV infection.
AB  - There is a significant prevalence (20%-80% depending on the population and the
      study) of lipid disorders and other cardiovascular risk factors in people living
      with HIV infection. This review focuses on HIV and HIV treatment-associated
      metabolic and cardiovascular concerns, including dyslipidemias, lipodystrophy
      syndromes, endothelial dysfunctions, and associated metabolic events such as
      insulin resistance. Emerging hypotheses of the underlying pathophysiology of
      these issues, with impact on selection of specific antiretroviral treatment (ART)
      strategies, therapy, and preventive approaches to decreasing cardiovascular risk
      and other problems associated with these syndromes are discussed. Screening for
      cardiovascular risk as part of the decision of starting antiretroviral therapy,
      and during care of patients with HIV regardless of ART therapy status, is
      suggested with particular areas of focus. Statins, other hyperlipidemic
      therapies, treatment for specific problems arising due to lipodystrophy, and
      implications on ART selection to avoid drug interactions and adverse effects are
      also discussed.

PMID- 21181312
TI  - 1H, 13C and 15N resonance assignments of SARS-CoV main protease N-terminal
      domain.
AB  - The main protease (M(pro)) of severe acute respiratory syndrome coronavirus (SARS
      CoV) plays an essential role in the extensive proteolytic processing of the viral
      polyproteins (pp1a and pp1ab), and it is an important target for anti-SARS drug
      development. SARS-CoV M(pro) is composed of a catalytic N-terminal domain and an
      alpha-helical C-terminal domain linked by a long loop. Even though the N-terminal
      domain of SARS-CoV M(pro) adopts a similar chymotrypsin-like fold as that of
      piconavirus 3C protease, the extra C-terminal domain is required for SARS-CoV
      M(pro) to be enzymatically active. Here, we reported the NMR assignments of the
      SARS-CoV M(pro) N-terminal domain alone, which are essential for its solution
      structure determination.

PMID- 21181313
TI  - Pediatric rheumatology in Southeast Asia: insights from the Singapore experience.
AB  - Pediatric rheumatology is a well-established subspecialty in just 4 of 11
      Southeast Asia countries. With the development of a dedicated pediatric
      rheumatology clinical program in Singapore and the establishment of an Internet
      based registry, insights into local disease descriptions and epidemiology are
      possible. Concurring with reports from other parts of Asia and the West, a
      comparable proportion of referrals were for nonrheumatic conditions, although
      specific disease distributions were different. Juvenile idiopathic arthritis
      (JIA), vasculitides, and systemic lupus erythematosus are among the common
      rheumatic diseases seen in Singapore. Other than Henoch-Schonlein purpura and
      Kawasaki disease, other forms of systemic vasculitides are rare. JIA subtype
      distribution was unique, with enthesitis-related JIA showing predominance.
      Epidemiologic data are limited. Singapore has less of a biologic accessibility
      issue than other countries in Southeast Asia due to a stronger economy and strong
      financial support from foundations/organizations. As a multicultural Asian
      society, Singapore has traditional/alternative medicine practice as part of its
      health care system. Raising pediatric rheumatic disease awareness in the medical
      community and among the public is crucial to improving referral behavior and
      avoiding diagnosis delay and improper management. An urgent need exists for
      pediatric rheumatologists in Southeast Asia. With many differences between the
      East and West, establishment of a local, comprehensive, hands-on pediatric
      rheumatology fellowship training program may be a better strategy to decrease the
      patient-to-doctor ratio, eventually leading to an improvement in overall
      childhood-onset rheumatic disease outcomes.

PMID- 21181314
TI  - A unifying hypothesis for scleroderma: identifying a target cell for scleroderma.
AB  - We propose that a recent change in the conception of the role of type 1
      interferon and the identification of adventitial stem cells suggests a unifying
      hypothesis for scleroderma. This hypothesis begins with vasospasm. Vasospasm is
      fully reversible unless, as proposed here, the resulting ischemia leads to
      apoptosis and activation of type 1 interferon. The interferon, we propose,
      initiates immune amplification, including characteristic scleroderma-specific
      antibodies. We propose that the interferon also acts on adventitial stem cells,
      producing myofibroblasts, rarefaction, and intimal hyperplasia--three morphologic
      changes that characterize this disease. Regulator of G-protein signaling 5
      (RGS5), a regulator of vasoactive G-protein-coupled receptors, is a cell type
      specific marker of pericytes and scleroderma myofibroblasts. RGS5 may provide a
      key link between initial hyperplasia and fibrosis in this disease.

PMID- 21181315
TI  - Aggressive osteoblastoma of the maxilla: a case report and review of the
      literature.
AB  - Aggressive osteoblastoma is a rare primary bone neoplasm with the potential for
      local invasion and recurrence. While the vertebrae or long bones are most
      commonly affected, few well-documented cases have been reported in the jaws. A 25
      year-old man presented with a palatal mass of several months' duration. He
      reported the lesion had undergone gradual enlargement and, while generally
      asymptomatic, had recently become increasingly painful. An incisional biopsy was
      interpreted as "osteoblastic neoplasm" most suggestive of osteoblastoma. However,
      final diagnosis was deferred until the resection specimen could be evaluated.
      Following partial maxillectomy, histopathologic examination revealed a
      proliferation of large epithelioid cells with eccentric nuclei and prominent
      nucleoli associated with broad, irregular deposits of osteoid and trabeculae of
      bone. The lesional cells exhibited minimal pleomorphism with infrequent, normal
      appearing mitotic figures and numerous osteoclast-like giant cells were observed
      within an associated loose fibrovascular stroma. Transformation of "blue bone" to
      more organized eosinophilic trabeculae of woven bone was noted at the periphery
      of the lesion and there was no evidence of invasion. A diagnosis of aggressive
      osteoblastoma was made. Previous reports of gnathic aggressive osteoblastoma are
      reviewed and the features that distinguish this process from conventional
      osteoblastoma or osteoblastoma-like osteosarcoma are presented.

PMID- 21181316
TI  - Repeated donor lymphocyte infusions overcome a myeloid sarcoma of the stomach
      resulting from a relapse of acute myeloid leukemia after allogeneic cell
      transplantation in long-term survival of more than 10 years.
AB  - A patient with acute myeloid leukemia had a relapse with a myeloid sarcoma of the
      stomach 32 months after allogeneic bone marrow transplantation. The patient was
      treated with the first donor lymphocyte infusion (DLI) and one course of
      induction chemotherapy. Due to severe infectious complication after chemotherapy,
      the patient could not continue chemotherapy. Subsequently, the patient was
      treated with a total of 13 cycles of DLI at 1-2 month intervals. Complete
      remission was achieved and neither relapse nor graft versus host disease has
      occurred during a follow-up of more than 10 years.

PMID- 21181317
TI  - MR imaging of triple-negative breast cancer.
AB  - Little is known about the MR imaging features of triple-negative breast cancer
      (TNBC), but TNBC has a worse prognosis because it has no effective therapeutic
      targets, such as estrogen receptor for endocrine therapy and human epidermal
      growth factor receptor 2 (HER2) for anti-HER2 therapy. MR findings of a unifocal
      lesion, mass lesion type, smooth mass margin, rim heterogeneous enhancement,
      persistent enhancement pattern, and very high signal intensity on T2-weighted
      images are typical features of breast MR imaging associated with TNBC. Although
      TNBC can mimic a benign morphology, the early MR imaging recognition of TNBC
      could assist in both the pretreatment planning and the prognosis, as well as
      adding to our understanding of the biological behavior of TNBC.

PMID- 21181318
TI  - Mutations in the epidermal growth factor receptor gene in non-small cell lung
      cancer: Impact on treatment beyond gefitinib and erlotinib.
AB  - Epidermal growth factor receptor (EGFR)-activating mutations in non-small cell
      lung cancer (NSCLC) are molecular targets for treatment with gefitinib and
      erlotinib, often resulting in improved response and prolonged progression-free
      survival. Resistance to these drugs, which develops during treatment, is a
      problem of paramount importance. Several mechanisms of "acquired resistance" have
      been discovered and treatments for this specific entity are on the horizon.

PMID- 21181319
TI  - Safety and tolerability of high-dose intravenous esomeprazole for prevention of
      peptic ulcer rebleeding.
AB  - INTRODUCTION: Efficacy of a continuous high-dose intravenous infusion of
      esomeprazole, followed by an oral regimen after successful endoscopic therapy for
      peptic ulcer bleeding (PUB) was established in the PUB study (ClinicalTrials. gov
      identifier: NCT00251979). Mortality rates and detailed safety and tolerability
      results from this study are reported here. METHODS: This was a double-blind,
      randomized study in patients >=18 years with overt signs of upper
      gastrointestinal bleeding, following endoscopic diagnosis of a single gastric or
      duodenal ulcer (>=5 mm) with stigmata indicating current/ recent bleeding
      (Forrest class Ia, Ib, IIa, or IIb). Postendoscopic hemostasis, patients received
      intravenous esomeprazole (80 mg/30 minutes, then 8 mg/hour for 71.5 hours) or
      placebo. Postinfusion, all patients received open-label oral esomeprazole 40 mg
      once daily for 27 days. Mortality rates were analyzed using Fisher's exact test;
      other safety variables were analyzed descriptively. RESULTS: A total of 767
      patients were randomized; 764 comprised the safety analysis set (375 patients
      received esomeprazole, 389 placebo). Baseline characteristics were similar across
      the two treatment groups. Three deaths from the esomeprazole treatment group and
      eight from the placebo group occurred during the trial (0.8% versus 2.1%;
      P=0.22). From these 11 all-cause deaths, one (esomeprazole group; rebleeding from
      duodenal ulcer) occurred during the 72-hour intravenous treatment phase. Adverse
      event (AE) frequency was similar for the two groups over the intravenous
      treatment phase (esomeprazole, 39.2%; placebo, 41.9%), with gastrointestinal
      disorders being most commonly reported (12.3% and 19.8%, respectively). Serious
      AEs were mostly related to bleeding events. Infusion-site reactions (mild,
      transient) were reported in 4.3% of esomeprazole-treated patients versus 0.5% of
      placebo patients. These did not lead to treatment discontinuation. CONCLUSION:
      Esomeprazole, given as a continuous high-dose intravenous infusion followed by an
      oral regimen after successful endoscopic therapy for PUB, was well tolerated,
      with no apparent safety concerns from either the high-dose intravenous treatment
      or oral phases.

PMID- 21181320
TI  - Cell therapy for cardiovascular disease: a comparison of methods of delivery.
AB  - The field of myocardial regeneration utilizing novel cell-based therapies, gene
      transfer, and growth factors may prove to play an important role in the future
      management of ischemic heart disease and cardiomyopathy. Phases I and II clinical
      trials have been published for a variety of biologics utilizing four methods of
      delivery: systemic infusion, intracoronary infusion, transvenous coronary sinus,
      and intramyocardial. This review discusses the advantages and disadvantages of
      the delivery approaches above.

PMID- 21181321
TI  - Non-enhanced cardiac computed tomography-still an open book.

PMID- 21181322
TI  - Vascular adaptations to hypobaric hypoxic training in postmenopausal women.
AB  - The objective of this study was to examine the effects of exercise training in
      hypoxia on arterial stiffness and flow-mediated vasodilation (FMD) in
      postmenopausal women. Sixteen postmenopausal women (56+/-1 years) were assigned
      to a normoxic exercise group (Normoxic group, n=8) or a hypoxic exercise group
      (Hypoxic group, n=8). The Hypoxic group performed exercise under hypobaric
      hypoxic conditions corresponding to 2000 m above sea level, and was exposed to
      these conditions for 2 h per session. Aquatic exercise was performed at an
      intensity of around 50% peak oxygen uptake for 30min, 4days per week, for 8
      weeks. Arterial stiffness was assessed by brachial-ankle pulse wave velocity
      (baPWV), and FMD was evaluated by peak diameter of the popliteal artery during
      reactive hyperemia. After the 8 weeks of training, the Normoxic group showed no
      significant changes. In contrast, baPWV (P < 0.05) was significantly reduced and
      peak diameter (P<0.05) and %FMD (P<0.01) were significantly increased in the
      Hypoxic group after training. These results suggest that exercise training under
      mild intermittent hypoxic conditions could more effectively reduce arterial
      stiffness in postmenopausal women, compared with exercise training performed at
      the same relative intensity under normoxic conditions. Our data also indicate
      that hypoxic exercise training may induce vascular functional adaptation, for
      example an increase in FMD response. These findings therefore could have
      important implications for the development of a new effective exercise
      prescription program.

PMID- 21181323
TI  - A mathematical model for lactate transport to red blood cells.
AB  - A simple mathematical model for the transport of lactate from plasma to red blood
      cells (RBCs) during and after exercise is proposed based on our experimental
      studies for the lactate concentrations in RBCs and in plasma. In addition to the
      influx associated with the plasma-to-RBC lactate concentration gradient, it is
      argued that an efflux must exist. The efflux rate is assumed to be proportional
      to the lactate concentration in RBCs. This simple model is justified by the
      comparison between the model-predicted results and observations: For all 33 cases
      (11 subjects and 3 different warm-up conditions), the model-predicted time
      courses of lactate concentrations in RBC are generally in good agreement with
      observations, and the model-predicted ratios between lactate concentrations in
      RBCs and in plasma at the peak of lactate concentration in RBCs are very close to
      the observed values. Two constants, the influx rate coefficient C (1) and the
      efflux rate coefficient C (2), are involved in the present model. They are
      determined by the best fit to observations. Although the exact electro-chemical
      mechanism for the efflux remains to be figured out in the future research, the
      good agreement of the present model with observations suggests that the efflux
      must get stronger as the lactate concentration in RBCs increases. The
      physiological meanings of C (1) and C (2) as well as their potential applications
      are discussed.

PMID- 21181324
TI  - Portacaval shunting attenuates portal hypertension and systemic hypotension in
      rat anaphylactic shock.
AB  - Anaphylactic shock in rats is characterized by antigen-induced hepatic
      venoconstriction and the resultant portal hypertension. We determined the role of
      portal hypertension in anaphylactic hypotension by using the side-to-side
      portacaval shunt- and sham-operated rats sensitized with ovalbumin (1 mg). We
      measured the mean arterial blood pressure (MAP), portal venous pressure (PVP),
      and central venous pressure (CVP) under pentobarbital anesthesia and spontaneous
      breathing. Anaphylactic hypotension was induced by an intravenous injection of
      ovalbumin (0.6 mg). In sham rats, the antigen caused not only an increase in PVP
      from 11.3 cmH(2)O to the peak of 27.9 cmH(2)O but also a decrease in MAP from 103
      mmHg to the lowest value of 41 mmHg. CVP also decreased significantly after the
      antigen. In the portacaval shunt rats, in response to the antigen, PVP increased
      slightly, but significantly, to the peak of 17.5 cmH(2)O, CVP did not decrease,
      and MAP decreased to a lesser degree with the lowest value being 60 mmHg. These
      results suggest that the portacaval shunt attenuated anaphylactic portal
      hypertension and venous return decrease, partially preventing anaphylactic
      hypotension. In conclusion, portal hypertension is involved in rat anaphylactic
      hypotension presumably via splanchnic congestion resulting in decreased venous
      return and thus systemic arterial hypotension.

PMID- 21181326
TI  - Preoperative patient education for breast reconstruction: a systematic review of
      the literature.
AB  - This study aims to assess the current state of patient educational tools
      available for the purposes of educating women about postmastectomy breast
      reconstruction. A systematic review of the English language literature was
      conducted between the years 1966 and 2009 of all studies pertaining to the use of
      educational materials for breast reconstruction. MEDLINE, CINAHAL, PsycINFO,
      EMBASE, SCOPUS, and the Science Citation Index were searched. Only studies that
      both employed and evaluated a patient educational tool in the setting of
      postmastectomy reconstruction were selected for review. Qualifying studies were
      then evaluated with respect to their study design, sample size, and outcome
      measure evaluated. Each educational tool identified was similarly evaluated with
      respect to its development process, content, and educational medium. A total of
      497 articles were retrieved. Of these, only seven met our inclusion criteria.
      These publications evaluated a total of seven educational tools. Among them were
      employed various mediums including written, visual, and audio materials. Detailed
      review revealed that the development of only one educational program included an
      educational needs assessment. Only two of the seven studies identified evaluated
      the efficacy of their educational tool using a randomized controlled trial study
      design. Outcome measures evaluated varied among the studies identified and
      included: knowledge gains (n = 4), the 'yes' or 'no' decision to undergo
      reconstruction (n = 3), satisfaction with decision regarding reconstruction (n =
      1), decisional conflict (n = 3), and type of reconstruction (n = 3). This review
      highlights the need for well-designed, methodologically sound research into
      patient education regarding breast reconstruction. Such information is invaluable
      in developing patient education programs and decision aids that aim at patient
      empowerment.

PMID- 21181325
TI  - Population based study to assess prevalence and risk factors of gastroesophageal
      reflux disease in a high altitude area.
AB  - AIM: We did a population-based cross-sectional study to investigate the
      prevalence and risk factors of gastroesophageal reflux disease (GERD) in a high
      altitude area. METHODS: An observational study using a validated questionnaire
      consisting of demographic, lifestyle and dietary characteristics was administered
      in an interview based format by two clinicians on a sample of adult population
      residing in urban area and rural high altitude areas of Ladakh. Presence of GERD
      was defined as a score of >=4 using a previously validated symptom score based on
      the severity and frequency of heartburn and regurgitation. Other factors studied
      were body mass index (BMI), oxygen saturation levels by pulse oximetry and serum
      lipid profile. A multivariate analysis was done to find out risk factors for
      symptomatic GERD. RESULTS: Of the 905 subjects analyzed, there were 399 (44.1%)
      men; 469 (51.8%) were from rural background and 722 (79.8%) lived in areas 3,000
      m above sea level. Symptomatic GERD was present in 169 (18.7%) subjects.
      Regurgitation occurred once a week in 34.8% and heartburn occurred in 42.9% of
      subjects. Sixteen (9.5%) had moderate-severe disease activity while 153 (90.5%)
      had mild disease. Three hundred and eighty-eight (42.7%) and 315 (34.8%) subjects
      had symptom of heartburn and regurgitation (at least once a week), respectively.
      On multivariate analysis, risk factors for GERD were age <=50 years (OR: 1.508,
      95% CI: 1.028-2.213), sedentary lifestyle (OR: 2.78, 95% CI: 1.016-7.638), lower
      intake of salt tea (OR: 1.663, 95% CI: 1.014-2.726); whereas the protective
      factors were no intake of meat (OR: 0.841, 95% CI: 0.715-0.990), intake of fresh
      fruits >=1/week (OR: 0.631, 95% CI: 0.409-0.973), and serum LDL <=150 mg/dL (OR:
      0.435, 95% CI: 0.218-0.868). CONCLUSION: This population-based study in a high
      altitude area in India suggests a high prevalence (18.7%) of GERD. A younger age
      group, sedentary lifestyle, serum LDL >150 mg/dL, high consumption of meat, low
      consumption of salted tea and low consumption of fresh fruits were significant
      risk factors for development of GERD.

PMID- 21181327
TI  - [The reemergence of the Chikungunya virus in Reunion Island on 2010: evolution of
      the mosquito control practices].
AB  - The re-emergence of local transmission of chikungunya virus caused by Aedes
      albopictus since March 2010 in the Reunion Island, French territory in the
      southwest Indian Ocean, calls for better epidemiological surveys, vector control,
      and community-based chikungunya control. This paper describes the strategy and
      the new ways of vector control applied since the last major chikungunya virus
      outbreak in 2005-2007, and the high levels of collaboration with mayors and local
      associations for community involvement. Between March 17, 2010 (first chikungunya
      case) and July 1, 2010, 313 cases were investigated, 13,036 premises inspected,
      and 34,393 premises concerned by spatial treatment. The traditional entomologic
      indices don't explain the distribution map of chikungunya cases, and many other
      factors have to be measured for evaluating the risk of transmission, such as
      lifestyle, habitat, and the kind of environment the people live in. A big
      information campaign was conducted beside the implementation of traditional
      mosquito control techniques. The two themes of this campaign are environmental
      management and individual protection, considered as important components of
      chikungunya prevention. The outcome of the mosquito control strategy demonstrates
      that community participation is not enough, and more studies are required to
      define new ways of communication for promoting community-oriented activities to
      prevent chikungunya epidemics.

PMID- 21181328
TI  - [Epidemic of influenza A(H1N1) 2009 in Reunion Island: epidemiological data].
AB  - In Reunion Island, a French subtropical island located in the southern
      hemisphere, the monitoring of the epidemiological dynamics of the epidemic linked
      to the emergence of pandemic virus A(H1N1) 2009 was achieved through the regular
      influenza surveillance system which has been reinforced on that occasion. It was
      mainly based on a network of sentinel physicians, combined with virologic
      monitoring, and on surveillance of severe cases and deaths. The data were
      analyzed and retroinformation was distributed according to a weekly frequency.
      The first imported case was confirmed on July 5, 2009 in a traveler arriving from
      Australia, whereas the first autochthonous cases were reported on July 23. The
      epidemic peak was reached in five weeks and the duration of the whole epidemic
      episode was 9 weeks. Pandemic virus has quickly supplanted seasonal viruses that
      had begun to circulate. The estimated attack rate for symptomatic cases of
      infection with virus influenza A(H1N1) 2009 was 12.85%. The hospitalization rate
      was 32 per 10,000 estimated cases, and 24 people had a serious form requiring
      care in ICU. Among death certificates received at the regional office for health
      and social affairs, 14 mentioned the influenza, including 7 in whom the pandemic
      virus has been laboratory confirmed. These deaths occurred in patients
      significantly younger than usually observed in Reunion Island during the seasonal
      influenza epidemics. Overall, the epidemic intensity and severity have been
      similar to those of seasonal influenza in Reunion Island.

PMID- 21181329
TI  - [Influenza A (H1N1) 2009 surveillance on Mayotte island: the challenge of setting
      up a new system facing the pandemic].
AB  - In response to the threat of the pandemic influenza A (H1N1) 2009 virus in
      Mayotte Island, influenza surveillance needed to be set up in a matter of weeks,
      to detect the introduction of the pandemic virus and monitor its spread and
      impact on public health. Surveillance was based on different systems, including a
      sentinel practitioner network for influenza-like illness, surveillance of the
      activity at the hospital emergency departments, virological surveillance,
      surveillance of severe and fatal cases, and data collection on sale of
      antipyretic and anti-viral drugs. Despite some weaknesses of the surveillance,
      results showed a good correlation between all systems, describing an epidemic
      period of approximately 8-9 weeks, with a peak between weeks 37 and 40, followed
      by a rapid decrease. Besides allowing monitoring and describing the impact of
      pandemic H1N1 2009 virus in Mayotte, the surveillance system provided an
      opportunity to create networks and globally strengthened surveillance of
      infectious diseases in the Island.

PMID- 21181330
TI  - [Epidemic of influenza A(H1N1) 2009 in the French overseas territories of the
      Americas: epidemiological surveillance set up and main results, April 2009
      January 2010].
AB  - Guadeloupe, French Guiana, Martinique, St. Martin and St. Barthelemy were the
      French territories most exposed to the new influenza A(H1N1)v, and adequate
      epidemiological surveillance tools were promptly developed in order to detect its
      emergence. The first stage, "containment phase", consisted in detection and
      management of individual cases. Then, when an autochthonous A(H1N1)v circulation
      was confirmed, its evolution has been monitored within the whole population,
      mainly through data collected from sentinel doctors' networks and virological
      surveillance. This allowed to detect very early the occurrence of epidemics, and
      to follow their evolution until they were over. Like all the other Caribbean
      countries, the five French overseas territories were hit by an outbreak of
      influenza A(H1N1)v. Although they had globally similar characteristics, each
      epidemic had its specificity in terms of scale and severity. They started between
      August and September 2009 in four of the five territories, while the last one,
      St. Barthelemy, was not affected until the end of the year. Attack rate estimates
      varied from 28 to 70 per 1000 inhabitants according to the territory, and
      hospitalisation rate varied from 4.3 to 10.3 per 1000 cases. Severity rate didn't
      reach 1 per 1000 cases in any of the territories. Compared to metropolitan
      France, the surveillance system presented several strengths, including the pre
      existence of both an active sentinel network and an expert committee on emerging
      diseases in each territory. On the other hand, specific difficulties appeared,
      notably linked with logistical aspects of virological surveillance and the co
      circulation of dengue virus in Guadeloupe and St. Barthelemy. Despite these
      difficulties, the different tools allowed early detection of the epidemics and
      follow-up of their evolution. All of them lead to very concordant results,
      suggesting that they are completely appropriate to monitor a potential new
      epidemic wave.

PMID- 21181332
TI  - Early results and complications of colorectal laparoscopic surgery and analysis
      of risk factors in 492 operated cases.
AB  - This study aimed to evaluate the early results of colorectal laparoscopic surgery
      with special attention to surgical and medical complications. The risk factors of
      such surgery are also investigated on the basis of a large series of operated
      cases: the preoperative knowledge of such factors could guide the operative
      program and the postoperative treatment with reduction of complications and
      improvement of the outcome. Between 1998 and 2008, 492 patients had been
      submitted to colorectal laparoscopic surgery by the same team: 387 for cancer and
      105 for benign disease. All colorectal surgical operations are included in the
      series. No selection of the patients was made: laparoscopy was performed in all
      cases accepting the procedure. Several risk factors have been analysed in cases
      of fistula (age, pathology sex, type of the operation, cancer stages,
      preoperative radiochemotherapy, stool diversion and team experience) and in cases
      of medical complications (age, pathology, cancer stages and type of operation).
      The overall results in this series of laparoscopic colorectal operated cases are
      similar to other results published at present by the main surgical Department all
      over the world; no mortality and low number of medical (2.4%) and surgical
      complications (9.3%), with no differences also with the best open surgery series.
      Complete or partial conversion to open surgery was required in few cases (1.2%)
      and same others (1.4%) were operated again for bleeding or sudden anastomotic
      leakage. Regarding the risk factors in such surgery, a good correlation has been
      discovered between anastomotic leakage and the team experience, the age over 70
      of the patients, the rectal tumour site in man, the advanced tumour stages, the
      previous radiochemotherapy, while medical complications seem to depend on
      advanced patients age and advanced cancer stages. Laparoscopic colorectal surgery
      at present is going to be considered the gold standard in the large majority of
      colorectal diseases including all cancer stages in the preoperative balance and
      in the early postoperative follow-up a special attention is required to same risk
      factors like the advanced patients age, the extended cancers, the low positioned
      rectal tumours. Complications are more frequent at the beginning of the
      experience of the surgical team and if more than one risk factors coexist, but it
      do not represent contraindication to laparoscopic surgery.

PMID- 21181331
TI  - Diaphragm rupture in a liver transplant patient under chronic immunosuppressive
      therapy with sirolimus: rare complication after liver transplantation.
AB  - A diaphragm rupture is a very rare event. A variety of conditions such as
      coughing, delivery, and vigorous exercise causing a sudden increase of the intra
      abdominal pressure can result in diaphragm rupture [1]. The diagnosis can be
      difficult because of non-specific symptoms and no history of blunt or penetrating
      trauma. Due to anatomical reasons, diaphragmatic lesions in the left side are
      more common than those in the right side. Chronic immunosuppressive therapy in
      transplanted patients, especially with antiproliferative drugs such as mTOR
      inhibitor, has been considered as a risk factor for the development of incisional
      hernia [2, 3]. We present the case of diaphragm rupture in a liver transplant
      patient under chronic immunosuppressive therapy with sirolimus.

PMID- 21181333
TI  - Molecular characterisation of the full-length genome of olive latent virus 1
      isolated from tomato.
AB  - Olive latent virus 1 (OLV-1) is a species of the Necrovirus genus. So far, it has
      been reported to infect olive, citrus tree and tulip. Here, we determined and
      analysed the complete genomic sequence of an isolate designated as CM1, which was
      collected from tomato plant in the Wielkopolska region of Poland and represents
      the prevalent isolate of OLV-1. The CM1 genome consists of monopartite single
      stranded positive-sense RNA genome sized 3,699 nt with five open reading frames
      (ORFs) and small inter-cistronic regions. ORF1 encodes a polypeptide with a
      molecular weight of 23 kDa and the read-through (RT) of its amber stop codon
      results in ORF1 RT that encodes the virus RNA-dependent RNA polymerase. ORF2 and
      ORF3 encode two peptides, with 8 kDa and 6 kDa, respectively, which appear to be
      involved in cell-to-cell movement. ORF4 is located in the 3' terminal and encodes
      a protein with 30 kDa identified as the viral coat protein (CP). The differences
      in CP region of four OLV-1 isolates whose sequences have been deposited in
      GenBank were observed. Nucleotide sequence identities of the CP of tomato CM1
      isolate with those of olive, citrus and tulip isolates were 91.8%, 89.5% and
      92.5%, respectively. In contrast to other OLV-1 isolates, CM1 induced necrotic
      spots on tomato plants and elicited necrotic local lesions on Nicotiana
      benthamiana, followed by systemic infection. This is the third complete genomic
      sequence of OLV-1 reported and the first one from tomato.

PMID- 21181334
TI  - Mapping of QTLs governing agronomic and yield traits in chickpea.
AB  - Chickpea is one of the most important leguminous cool season food crops,
      cultivated prevalently in South Asia and Middle East. The main objective of this
      study was to identify quantitative trait loci (QTLs) associated with seven
      agronomic and yield traits in two recombinant inbred line populations of chickpea
      derived from the crosses JG62 * Vijay (JV population) and Vijay * ICC4958 (VI
      population) from at least three environments. Single locus QTL analysis involved
      composite interval mapping (CIM) for individual traits and multiple-trait
      composite interval mapping (MCIM) for correlated traits to detect pleiotropic
      QTLs. Two-locus analysis was conducted to identify the main effect QTLs (M-QTLs),
      epistatic QTLs (E-QTLs) and QTL * environment interactions. Through CIM analysis,
      a total of 106 significant QTLs (41 in JV and 65 in VI populations) were
      identified for the seven traits, of which one QTL each for plant height and days
      to maturity was common in both the populations. Six pleiotropic QTLs that were
      consistent over the environments were also identified. LG2 in JV and LG1a in VI
      contained at least one QTL for each trait. Hence, concentrating on these LGs in
      molecular breeding programs is most likely to bring simultaneous improvement in
      these traits.

PMID- 21181335
TI  - [Antithrombotic and anticoagulation therapy after stroke and transient ischemic
      attacks].
AB  - Patients with a transient ischemic attack (TIA) or ischemic stroke are at high
      risk for a recurrent stroke. Platelet inhibitors can reduce this risk in patients
      with non-cardioembolic stroke or TIA. Aspirin is used for secondary prevention in
      patients with a low risk of recurrent stroke while the combination of aspirin and
      dipyridamole or clopidogrel is recommended in patients with a higher risk.
      Patients with atrial fibrillation have a five-fold increased risk of stroke. In
      comparison to placebo oral anticoagulation reduces the risk of stroke by 60-70%
      in primary and secondary stroke prevention. Aspirin can still reduce the relative
      stroke risk by 22% in patients with atrial fibrillation who have
      contraindications against anticoagulation. Given the limitations of oral
      anticoagulation with vitamin K antagonists a new generation of anticoagulants is
      currently being investigated which include factor Xa inhibitors and direct
      thrombin antagonists. Dabigatran has been shown to be as efficacious as warfarin
      given at a lower dose and significantly more efficacious when administered at a
      higher dosage. Both cerebral and intracranial hemorrhages were reduced by 60-80%
      in patients treated with dabigatran when compared to warfarin.

PMID- 21181338
TI  - Ideotype root architecture for efficient nitrogen acquisition by maize in
      intensive cropping systems.
AB  - The use of nitrogen (N) fertilizers has contributed to the production of a food
      supply sufficient for both animals and humans despite some negative environmental
      impact. Sustaining food production by increasing N use efficiency in intensive
      cropping systems has become a major concern for scientists, environmental groups,
      and agricultural policymakers worldwide. In high-yielding maize systems the major
      method of N loss is nitrate leaching. In this review paper, the characteristic of
      nitrate movement in the soil, N uptake by maize as well as the regulation of root
      growth by soil N availability are discussed. We suggest that an ideotype root
      architecture for efficient N acquisition in maize should include (i) deeper roots
      with high activity that are able to uptake nitrate before it moves downward into
      deep soil; (ii) vigorous lateral root growth under high N input conditions so as
      to increase spatial N availability in the soil; and (iii) strong response of
      lateral root growth to localized nitrogen supply so as to utilize unevenly
      distributed nitrate especially under limited N conditions.

PMID- 21181339
TI  - A 60-year journey of mycorrhizal research in China: Past, present and future
      directions.
AB  - The significance of mycorrhizas (fungal roots in 90% of land plants) in plant
      nutrient acquisition and growth, element biogeochemical cycling and maintaining
      of terrestrial ecosystem structures has been globally established for more than
      120 years. Great progress in mycorrhizal research in the past 60 years (1950
      2009, 1981-2009 in particular) has also been made across China, particularly in
      the mainland, Hong Kong and Taiwan. For instance, a total of 20 new and
      approximately 120 records of arbuscular mycorrhizal (AM) fungal species, 30 new
      and approximately 800 records of ectomycorrhizal (EM) fungal species, a dozen of
      new and approximately 100 records of orchid mycorrhizal (OM) fungal species have
      been isolated by morphological observation and/or molecular identification in
      China since the 1950s. Great accomplishment has also been made in the following
      area, including fungal species richness and genetic structure, relationships
      between species composition and plant taxa, effects of mycorrhizal fungi on plant
      nutrient uptake and growth, resistances to pathogens and interactions with other
      soil microorganisms, potential of mycorrhizal fungi in phytoremediation and/or
      land reclamation, alterations of enzymatic activities in mycorrhizal plants, and
      elevated CO(2) and O(3) on root colonization and species diversity.
      Unfortunately, the international community cannot easily appreciate almost all
      Chinese mycorrhizal studies since the vast majority of them have been published
      in Chinese and/or in China-based journals. The aim of this review is to make a
      comprehensive exposure of the past and present China's major mycorrhizal research
      to the whole world, and then to suggest potential directions for the enhancement
      of future mycorrhizal research within and/or between the Chinese and
      international mycorrhizal community.

PMID- 21181340
TI  - Formaldehyde stress.
AB  - Formaldehyde, one of the most toxic organic compounds, is produced and processed
      in human cells. The level of human endogenous formaldehyde is maintained at a low
      concentration (0.01-0.08 mmol L(-1) in blood) under physiological conditions, but
      the concentration increases during ageing (over 65 years old). Clinical trials
      have shown that urine formaldehyde concentrations are significantly different
      between elderly Alzheimer's patients (n=91) and normal elderly volunteers (n=38)
      (P<0.001). Abnormally high levels of intrinsic formaldehyde lead to dysfunction
      in cognition such as learning decline and memory loss. Excess extracellular and
      intracellular formaldehyde could induce metabolic response and abnormal
      modifications of cellular proteins such as hydroxymethylation and
      hyperphosphorylation, protein misfolding, nuclear translocation and even cell
      death. This cellular response called formaldehyde stress is dependent upon the
      concentration of formaldehyde. Chronic impairments of the brain resulted from
      formaldehyde stress could be one of the mechanisms involved in the process of
      senile dementia during ageing.

PMID- 21181341
TI  - TEE monitoring for RA-horizontal paradoxical arterial air embolism during sitting
      position surgery.
AB  - A 36-year-old woman suffered meningioma in her right cerebellopontine angle. Air
      embolisms often complicate sitting-position surgeries. Because TEE guides the
      localization of central venous catheters and promptly locates air embolisms
      promptly enough for effective treatment, TEE is an effective monitoring method
      for sitting-position surgeries.

PMID- 21181342
TI  - Stable isotope labelled mass spectrometry for quantification of the relative
      abundances for expressed proteins induced by PeaT1.
AB  - The protein elicitor from the mycelium of Alternaria tenuissima has been
      isolated. The elicitor triggered resistance to the tobacco mosaic virus in
      tobacco by inducing relative oxygen species, but without causing hypersensitive
      necrosis. The elicitor is reported to impart resistance against Verticillium
      dahliae and to increase yield in cotton, but its mechanism is not yet clear. In
      this study, the stable isotope labelled mass spectrometry method was used to
      quantify the relative abundances of protein expression induced by PeaT1 in
      Arabidopsis. A significant difference in the relative abundances for the
      expression of different proteins related to metabolism, modification, regulatory,
      defense, stress and antioxidation was found in Arabidopsis.

PMID- 21181343
TI  - Modeling columnar spatiotemporal dynamics of nitric oxide as a primary
      controlling element of arteriole dilation during neurovascular coupling.
AB  - Although the mechanism of neurovascular coupling remains inadequately understood,
      physiological research has indicated that the dilation of arterioles located
      within the cerebral cortex column might represent the primary mechanism of
      hemodynamic response during neurovascular coupling. This study examined the
      spatiotemporal pattern of NO diffusion induced by functional stimuli at column
      spatial resolution. Our modeling makes it possible to explore the responses of
      mediating factors to functional stimuli from a four-dimensional view, which may
      lead the way to decoding the mechanism of neurovascular coupling.

PMID- 21181344
TI  - Endogenous enkephalin does not contribute to the cerebral anti-hyperalgesic
      action of gabapentin.
AB  - The aim of this study was to investigate the role of endogenous enkephalin in the
      cerebral antihyperalgesic action of gabapentin. Neuropathic pain models and
      antihyperalgesic effect of gabapentin were confirmed by the presentation and
      changes of mechanical allodynia and thermal hyperalgesia of operated mouse hind
      paws. The results suggested that endogenous enkephalin may not be involved in the
      antihyperalgesic effect of gabapentin.

PMID- 21181345
TI  - Effects of confined space and near vision stimulation on refractive status and
      vitreous chamber depth in adolescent rhesus monkeys.
AB  - This study aimed to investigate the effects of sustained near vision stimulation,
      on the refractive development and elongation of the vitreous chamber in
      adolescent rhesus monkeys. A total of 12 adolescent rhesus monkeys (1.5-2.0 years
      old) were randomly assigned to 3 groups. In groups A (n=4) and B (n=4), monkeys
      were reared in close-vision cages for 8 and 4 h d(-1), respectively; tiny
      granules were added on the cage floor to avoid visual deprivation and to
      encourage near gaze. In group C (n=4), monkeys were reared in open-vision cages,
      with non-granule food as a control. Vitreous chamber depth, refractive status,
      and corneal refractive power were assessed over 18 months. Paired t-test was used
      to compare the differences and a P-value<0.05 was considered to be statistically
      significant. In group A, vitreous chamber depth and optical axis elongated
      significantly, and refractive error shifted towards myopia during the observation
      period. In group B, vitreous chambers and optical axis elongated but the
      refractive power did not show significant changes. In group C, there was no
      significant elongation in vitreous chambers and optical axis, and the refractive
      power changed slightly towards hypermetropia. There were no significant changes
      in corneal refractive power in each group. Sustained near vision can promote
      vitreous chamber growth and induce myopic shifts in refractive power in
      adolescent monkeys. Our results demonstrate the potential for a primate model of
      near-work-related myopia.

PMID- 21181346
TI  - Identification of an avirulence gene, avrxa5, from the rice pathogen Xanthomonas
      oryzae pv. oryzae.
AB  - Xanthomonas oryzae pv. oryzae, the causal agent of bacterial blight in rice,
      interacts with rice plants in a gene-for-gene manner. The specificity of the
      interaction is dictated by avirulence (avr) genes in the pathogen and resistance
      (R) genes in the host. To date, no avr genes that correspond to recessive R genes
      have been isolated. We isolated an avrBs3/pthA family gene, avrxa5, from our
      previously isolated clone p58, which was originally from strain JXOIII. The
      avrxa5 gene converted the PXO99(A) strain from compatible to incompatible in rice
      cultivars containing the recessive xa5 gene, but not in those containing the
      dominant Xa5 gene. Sequencing indicated that avrxa5, which is highly similar to
      members of the avrBs3/pthA family, encodes a protein of 1238 amino acid residues
      with a conserved carboxy-terminal region containing three nuclear localization
      signals and a transcription activation domain. It has 19.5 34-amino-acid direct
      repeats, but the 13th amino acid is missing in the fifth and ninth repetitive
      units. Domain swapping of the repetitive regions between avrxa5 and avrXa7
      changed the avirulence specificity of the genes in xa5 and Xa7 rice lines,
      respectively. This indicates that avrxa5 is distinct from previously
      characterized avrBs3/pthA members. The specificity of avrxa5 toward recessive xa5
      in rice could help us better understand the molecular mechanisms of plant
      pathogen specific interactions.

PMID- 21181347
TI  - Ectopic expression of foxtail millet zip-like gene, SiPf40, in transgenic rice
      plants causes a pleiotropic phenotype affecting tillering, vascular distribution
      and root development.
AB  - Plant architecture determines grain production in rice (Oryza sativa) and is
      affected by important agronomic traits such as tillering, plant height, and
      panicle morphology. Many key genes involved in controlling the initiation and
      outgrowth of axillary buds, the elongation of stems, and the architecture of
      inflorescences have been isolated and analyzed. Previous studies have shown that
      SiPf40, which was identified from a foxtail millet (Setaria italica) immature
      seed cDNA library, causes extra branches and tillers in SiPf40-transgenic tobacco
      and foxtail millet, respectively. To reconfirm its function, we generated
      transgenic rice plants overexpressing SiPf40 under the control of the ubiquitin
      promoter. SiPf40-overexpressing transgenic plants have a greater tillering number
      and a wider tiller angle than wild-type plants. Their root architecture is
      modified by the promotion of lateral root development, and the distribution of
      xylem and phloem in the vascular bundle is affected. Analysis of hormone levels
      showed that the ratios of indole-3-acetic acid/zeatin (IAA/ZR) and
      IAA/gibberellic acid (IAA/GA) decreased in SiPf40-transgenic plants compared with
      wild-type plants. These findings strongly suggest that SiPf40 plays an important
      role in plant architecture.

PMID- 21181348
TI  - Combined effects of chromium and arsenic on rice seedlings (Oryza sativa L.)
      growth in a solution culture supplied with or without P fertilizer.
AB  - The growths of two rice genotypes (Jin23A and CDR22) under the coexistence of As
      and Cr in solution culture with and without P were investigated. The result
      showed that rice shoot dry weight decreased due to the complex contamination of
      As and Cr, however, the influences on plant height, root length and root dry
      weight were insignificant.

PMID- 21181349
TI  - A web-based platform for rice microarray annotation and data analysis.
AB  - Rice (Oryza sativa) feeds over half of the global population. A web-based
      integrated platform for rice microarray annotation and data analysis in various
      biological contexts is presented, which provides a convenient query for
      comprehensive annotation compared with similar databases. Coupled with existing
      rice microarray data, it provides online analysis methods from the perspective of
      bioinformatics. This comprehensive bioinformatics analysis platform is composed
      of five modules, including data retrieval, microarray annotation, sequence
      analysis, results visualization and data analysis. The BioChip module facilitates
      the retrieval of microarray data information via identifiers of "Probe Set ID",
      "Locus ID" and "Analysis Name". The BioAnno module is used to annotate the gene
      or probe set based on the gene function, the domain information, the KEGG
      biochemical and regulatory pathways and the potential microRNA which regulates
      the genes. The BioSeq module lists all of the related sequence information by a
      microarray probe set. The BioView module provides various visual results for the
      microarray data. The BioAnaly module is used to analyze the rice microarray's
      data set.

PMID- 21181350
TI  - Effective connectivity of dorsal and ventral visual pathways in chunk
      decomposition.
AB  - Chunk decomposition is defined as a cognitive process which breaks up familiar
      items into several parts to reorganize them in an alternative approach. The
      present study investigated the effective connectivity of visual streams in chunk
      decomposition through dynamic causal modeling (DCM). The results revealed that
      chunk familiarity and perceptual tightness made a combined contribution to
      highlight not only the "what" and the "where" streams, but also the effective
      connectivity from the left inferior temporal gyrus to the left superior parietal
      lobule.

PMID- 21181351
TI  - Two special topics on the avian influenza virus and on epigenetics, have drawn
      much attention.

PMID- 21181352
TI  - NF-kappaB, a hot topic in biochemical and medical studies in China.

PMID- 21181353
TI  - Sterility and fertility: Keys for crop production in China.

PMID- 21181355
TI  - Differentiation character of adult mesenchymal stem cells and transfection of
      MSCs with lentiviral vectors.
AB  - This study examined the differentiation character and pluripotency of mesenchymal
      stem cells (MSCs) under different conditions. Adult MSCs were initially isolated
      from the bone marrow of rats, cultured in vitro and identified by flow cytometry.
      After MSCs were transferred to osteogenic and adipogenic medium respectively, the
      morphological characterization of induced cells was observed. The expression of
      marker genes was detected by RT-PCR analysis. Then MSCs were transfected with
      lentiviral vectors pGC-FU-Sox9-EGFP. Enhanced green fluorescence protein (EGFP)
      expression and transfection efficiency were determined by fluorescence
      microscopy. The results demonstrated that EGFP caused no effect on the
      multilineage potential of adult MSCs. Sox9 gene expression of high level was
      maintained stable in the transfected MSCs and induced MSCs to differentiate into
      chondrocytes. Aggracan was positive in chondrogenic lineages and the expression
      of aggracan and type collagen II was significantly increased during MSCs
      chondrogenic differentiation. It was concluded that Sox9 gene-modified adult MSCs
      may be promising candidate cells for further studies on tissue engineering. EGFP
      facilitates the research on MSCs physiological behavior and application in tissue
      engineering during differentiation both in vitro and in vivo.

PMID- 21181356
TI  - GTP cyclohydrolase 1 gene 3'-UTR C+243T variant predicts worsening outcome in
      patients with first-onset ischemic stroke.
AB  - Tetrahydrobiopterin (BH4) is an essential cofactor for all three nitric oxide
      synthase (NOS isoforms), which plays an important role in vascular diseases. GTP
      cyclohydrolase 1 (GCH 1) is the first-step and rate-limiting enzyme for BH4
      biosynthesis in its de novo pathway. Common GCH1 gene variant C+243T in the 3'
      untranslated region predicts NO excretion. The present study examined the
      predictive role of GCH 1 gene 3'-UTR C+243T variant in the long-term outcome of
      ischemic stroke. A total of 142 patients with first-onset ischemic stroke were
      recruited and detected for genotype of GCH1 3'-UTR C+243T by a TaqMan SNP
      Genotyping assay. Subsequent vascular events and death were determined over a 5
      year follow-up period. The frequency of GCH1 3'-UTR +243 C/T or T/T genotype was
      significantly increased in patients with endpoint events as compared with those
      without events (74% vs 57.8%, P=0.06). Cox regression survival analysis indicated
      that an increased probability of death or new vascular events was found in
      patients with GCH1 3'-UTR +243 C/T or T/T genotype compared with those with GCH1
      3'-UTR C/C genotype (40.6% vs 25.5%), GCH1 3'-UTR +243 C/T or T/T genotype
      relative to GCH1 3'-UTR C/C genotype was associated with the increased risk of
      death or vascular events even after adjustment for other risk factors (OR=2.171,
      95% CI: 1.066-4.424, P=0.033). It was concluded that GCH1 3'-UTR C+243T variant
      was an independent predictor of worsening long-term outcomes in patients with
      first-onset ischemic stroke.

PMID- 21181357
TI  - The relationship of cystatin C, creatinine, estimated GFR, and cardiovascular
      events.
AB  - This study examined the predictive value of plasma cystatin C, creatinine and
      estimated glomerular filtration rate (eGFR) as risk factors for cardiovascular
      disease in Chinese. Plasma cystatin C and creatinine were measured in 466
      coronary heart disease (CHD) patients recruited from 4 hospitals and 349 healthy
      controls from local communities in Wuhan, China. Cockroft-Gault formula was used
      to estimate the glomerular filtration rate (GFR) after adjusting for body surface
      area. With each measure, the study population was divided into quintiles. The
      results showed that the patients had significantly higher levels of plasma
      cystatin C, creatinine, and lower level of eGFR than controls. Lower eGFR was
      associated with a higher risk of cardiovascular events. As compared with the
      first (highest) quintile, the hazard ratios (and 95% CIs) after multivariate
      adjustment for CHD were as follows: third quintile, 2.98 (1.54-5.78); fourth
      quintile, 3.34 (1.58-7.09); fifth quintile, 4.37(1.84-10.35). With higher
      cystatin C quintiles (>=1.00 mg/L and >=1.17 mg/L), the hazard ratios for CHD
      were 2.16 (1.23-3.81) and 2.34 (1.25-4.38), similar to those of creatinine 2.21
      (1.21-4.03) and 2.03 (1.07-3.84). However, it was plasma cystatin C not eGFR or
      creatinine had stronger association with ischemic stroke. The highest quintile
      had the hazard ratio of 4.51 (1.45-14.08) after multivariate adjustment. It was
      concluded that plasma cystatin C, associated with renal function, is not an
      independent risk factor for cardiovascular disease. eGFR is a better risk
      predictor for CHD than plasma cystatin C and creatinine. But for ischemic stroke,
      plasma cystatin C is a better risk factor than creatinine and estimated GFR.

PMID- 21181358
TI  - Ischemia-reperfusion injury up-regulates Pim-3 gene expression in myocardial
      tissue.
AB  - This study examined the effect of ischemia-reperfusion injury on the expression
      of Pim-3 gene in myocardial tissues and their underlying mechanism. Rat models of
      myocardial ischemia-reperfusion injury were established by ligating the left
      anterior descending coronary artery of the rats. A total of 30 SD male adult rats
      were randomly divided into 5 groups: group A (sham operation, n=6); group B (in
      which the rats were subjected to 15 min of ischemia by ligation of the left
      anterior descending coronary artery, n=6); group C (in which the rats received 30
      min of ischemia, n=6), group D and group E (in which the left anterior descending
      coronary artery of the rats were ligated for 30 min and then reperfused for 30
      min or 120 min, n=6 in each). The left ventricular tissues were removed
      immediately after the ischemia-reperfusion injury. Neonatal cardiomyocytes were
      cultured and treated with different concentrations of H(2)O(2) (0, 5, 10, 20
      MUmol/L) or tumor necrosis factor-alpha (TNF-alpha, 0, 1, 5, 10 ng/mL). The mRNA
      and protein expression of Pim-3 gene was determined by using RT-PCR, western
      blotting and immunohistochemistry. Additionally, neonatal cardiomyocytes were
      transfected with Pim-3 siRNA, and induced to develop apoptosis by using H(2)O(2).
      The results showed that normal myocardial tissues expressed a quantity of Pim-3
      gene mRNA and protein. Ischemia-reperfusion injury could up-regulate the mRNA and
      protein expression of Pim-3 gene in myocardial tissues. Furthermore, H(2)O(2) but
      not TNF-alpha up-regulated the Pim-3 gene expression in cultured cardiomyocytes.
      And Pim-3 silencing failed to strengthen the H(2)O(2)-inducing apoptosis in
      cardiomyocytes. It was concluded that ischemia-reperfusion injury up-regulated
      the Pim-3 gene expression through oxidative stress signaling pathway in
      myocardial tissues.

PMID- 21181359
TI  - Effects of cadmium on telomerase activity, expressions of TERT, c-myc and P53,
      and apoptosis of rat hepatocytes.
AB  - This study investigated the effect of cadmium on the telomerase activity, the
      expression of TERT, c-myc and p53 and the apoptosis of rat hepatocytes. The rats
      were administrated 5, 10 and 20 MUmol/kg cadmium chloride intraperitoneally and
      sacrificed 48 h after the initial treatment. The telomerase activity of the rat
      hepatocytes was measured by the telomeric repeat amplification protocol (TRAP),
      and apoptosis was detected by flow cytometry. The mRNA expressions of TERT, c-myc
      and p53 were measured by reverse transcription-polymerase chain reaction (RT
      PCR). C-myc and P53 proteins were determined by immunochemistry. The results
      showed that cadmium chloride increased the hepatocellular telomerase activity in
      a dose-dependant manner and induced the apoptosis of hepatocytes significantly.
      The value of relative coefficient between the telomerase activity and the
      apoptosis rate was 0.9398. RT-PCR revealed that specific bands corresponding to
      the TERT mRNA, c-myc mRNA, and p53 mRNA were displayed at 185, 342 and 538 bp
      respectively. Cadmium chloride could substantially increase the mRNA expressions
      of TERT, c-myc and p53 in rat hepatocytes, as compared with control. Moreover,
      cadmium chloride at the doses of 5, 10 and 20 MUmol/kg could increase the content
      of P53 protein in rat hepatocytes obviously, but only that at the doses of 10 and
      20 MUmol/kg substantially promoted the c-myc protein level in rat hepatocytes.
      Our study herein suggested that cadmium may contribute to the carcinogenesis by
      activating telomerase, and overexpressing the mRNAs of TERT, c-myc and p53, and
      causing apoptosis of normal cells.

PMID- 21181360
TI  - The relationship between problem behavior and neurotransmitter deficiency in
      adolescents.
AB  - This study examined the association of problem behavior with neurotransmitter
      deficiency in adolescents, which would provide new insights into behavioral
      problems. A total of 1259 students of the seventh grade from 4 middle schools in
      Wuhan city located in the central China were recruited. With the approval of
      school and parents, they were invited to complete the Youth Self-Report (YSR)
      questionnaire and Symptom Scale of Neurotransmitter Deficiency (SSND)
      questionnaire. Pearson's bivariate correlation analysis showed that the
      correlation coefficients between each subscale of YSR and SSND ranged from 0.24
      to 0.61 with all P<0.01. Canonical correlation analysis indicated that
      anxiety/depression was interrelated with insufficiency of GABA and 5-HT;
      aggressive behavior was associated with inadequate GABA; famine of DA influenced
      the attention problems. It was concluded that neurotransmitter deficiency may
      cause a series of behavioral and mental problems.

PMID- 21181361
TI  - Short-term impact of cognition-motivation-emotional intelligence-resistance
      skills program on drug use prevention for school students in Wuhan, China.
AB  - Drug abuse continues to be a serious public health threat worldwide. Most drug
      abuse prevention research has been conducted with predominantly American or
      European adolescent populations. Little is known about approaches that work best
      to prevent the initiation of Chinese adolescent drug use. For targeting risk
      factors of drug initiation in Chinese adolescents, a school-based health
      intervention program named "Cognition-Motivation-Emotional Intelligence
      Resistance Skills" (CMER) was developed to enhance cognition upon drug use, to
      decrease motivation of drug use and to improve emotional adjusting and drug
      resistance skills in this study. A total of 798 students from 3 senior high
      schools in Wuhan, a city in central China, were assigned randomly to intervention
      and control groups. The intervention group received the CMER program in which
      knowledge, development of positive attitude and motivation towards drugs and
      training of peer resistance skills were basic elements. The immediate impact was
      compared by measuring the above mentioned elements prior to and three-month after
      the training session. Students from both groups were asked to complete a self
      administered questionnaire. The questionnaire included demographic items, self
      reported drug use behavior, cognition, attitude, and motivation associated with
      the initiation of drug use and resistance skills. Three months after the
      intervention, significant effects were found on "illegal substance use at least
      once" (P<0.05) between the intervention and control groups. Immediate effects of
      the intervention were also found on knowledge, motivation and peer resistance
      skills (P<0.05), but there was no clear evidence for any effects on attitude
      towards substance use (P>0.05). It was concluded that the CMER program, which
      significantly increased the knowledge of drugs and peer resistance skills, was
      effective in the drug abuse prevention in a sample of school students in Wuhan,
      China.

PMID- 21181362
TI  - All-trans retinoic acid diminishes collagen production in a hepatic stellate cell
      line via suppression of active protein-1 and c-Jun N-terminal kinase signal.
AB  - Following acute and chronic liver injury, hepatic stellate cells (HSCs) become
      activated to undergo a phenotypic transformation into myofibroblast-like cells
      and lose their retinol content, but the mechanisms of retinoid loss and its
      potential roles in HSCs activation and liver fibrosis are not understood. The
      influence of retinoids on HSCs and hepatic fibrosis remains controversial. The
      purpose of this study was to evaluate the effects of all-trans retinoid acid
      (ATRA) on cell proliferation, mRNA expression of collagen genes [procollagen
      alpha1 (I), procollagen alpha1 (III)], profibrogenic genes (TGF-beta(1), CTGF,
      MMP-2, TIMP-1, TIMP-2, PAI-1), fibrolytic genes (MMP-3, MMP-13) and the upstream
      element (JNK and AP-1) in the rat hepatic stellate cell line (CFSC-2G). Cell
      proliferation was evaluated by measuring BrdU incorporation. The mRNA expression
      levels of collagen genes [procollagen alpha1 (I), procollagen alpha1 (III)],
      profibrogenic genes (TGF-beta(1), CTGF, MMP-2, TIMP-1, TIMP-2, PAI-1), and
      fibrolytic genes (MMP-3, MMP-13) were quantitatively detected by using real-time
      PCR. The mRNA expression of JNK and AP-1 was quantified by RT-PCR. The results
      showed that ATRA inhibited HSCs proliferation and diminished the mRNA expression
      of collagen genes [procollagen alpha1 (I), procollagen alpha1 (III)] and
      profibrogenic genes (TGF-beta(1), CTGF, MMP-2, TIMP-1, TIMP-2, PAI-1), and
      significantly stimulated the mRNA expression of MMP-3 and MMP-13 in HSCs by
      suppressing the mRNA expression of JNK and AP-1. These findings suggested that
      ATRA could inhibit proliferation and collagen production of HSCs via the
      suppression of active protein-1 and c-Jun N-terminal kinase signal, then decrease
      the mRNAs expression of profibrogenic genes (TGF-beta(1), CTGF, MMP-2, TIMP-1,
      TIMP-2, PAI-1), and significantly induce the mRNA expression of MMP-3 and MMP-13.

PMID- 21181363
TI  - Discovery of chrysoeriol, a PI3K-AKT-mTOR pathway inhibitor with potent antitumor
      activity against human multiple myeloma cells in vitro.
AB  - This study was designed to determine the impact of chrysoeriol on proliferation
      and cell cycle progression in the human multiple myeloma cell lines RPMI 8226 and
      KM3, and its related molecular mechanisms. Chryseoriol was identified by using
      the phosphorylated AKT-specific cytoblot high throughput assay. CCK-8 assay was
      employed to examine the growth inhibition rate and IC(50) (48 h) in peripheral
      blood mononuclear cells (PBMNCs), RPMI 8226 and KM3 cells treated with
      chrysoeriol at various concentrations. Cells were labeled with 5-6
      carboxyfluorescein diacetate succinimidyl ester (CFSE), and the proliferation
      dynamics was detected by flow cytometry and analyzed with ModFit software. The
      cell cycles of RPMI 8226 and KM3 cells were measured by flow cytometry when the
      IC(50) concentration of chrysoeriol was adopted. The alterations in cell-cycle
      related proteins (Cyclin B1, Cyclin D1, p21) and proteins in PI3K-AKT-mTOR
      pathway were determined by Western blot analysis. The results showed the
      proliferation of multiple myeloma cells was significantly inhibited by
      chrysoeriol, resulting in cell cycle arrest in G(2)/M phase. Chrysoeriol could
      significantly reduce the expression of p-AKT (s473) and p-4eBP1 (t37/46) protein,
      meanwhile enhanced Cyclin B1 and p21 protein expression. Similar effects were not
      observed in PBMNCs from normal donors. It was concluded that chrysoeriol was a
      selective PI3K-AKT-mTOR pathway inhibitor. It restrained the proliferation of
      human multiple myeloma cells, but didn't affect proliferation of PBMNCs from
      normal donors. It might exhibit the cell cycle regulatory effect via the
      inhibition of PI3K-AKT-mTOR signal pathway.

PMID- 21181364
TI  - Effects of simvastatin on the function of dendritic cells in patients with
      rheumatic arthritis.
AB  - The present study examined the functional profile of dendritic cells (DCs) in
      patients with rheumatoid arthritis (RA) and the effects of simvastatin on the
      function of DCs. A total of 40 patients who was recently diagnosed as having RA
      were equally assigned to two groups: the routine treatment group (group R) and
      the routine treatment plus simvastatin group (group R+S). Twenty healthy
      individuals served as control. The peripheral blood mononuclear cells (PBMCs)
      were isolated before and 4 weeks after the treatment and then cultured with
      interleukin-4 (IL-4) and granulocyte-macrophage colony stimulatory factor (GM
      CSF) to prepare mature DCs. The expression of co-stimulating factor CD86 on the
      surface of DCs was assessed by flow cytometry. And the stimulating capacity of
      DCs was measured by mixed lymphocyte reaction (MLR). The contents of cytokines in
      culture supernatants of DCs in MLR were detected by ELISA. Blood lipids and high
      sensitivity C-reactive protein (hs-CRP) were detected. The relationship between
      the expression of CD86 and the blood CRP level was also investigated. The results
      showed that, as compared with the control group, the CD86 expression and the
      level of cytokines secreted by DCs were significantly increased in RA patients
      and greater stimulating capacity of DCs in MLR was demonstrated in RA patients. T
      lymphocytes in MLR secreted higher levels of proinflammatory cytokines (IL-2, IL
      17, TNF-alpha and INF-gamma) and lower level of anti-inflammation cytokine (IL
      10). The function of DCs was markedly weakened and the level of hs-CRP and low
      density lipoprotein was substantially lowered in group R+S in comparison to group
      R. The CD86 expression was positively correlated with hs-CRP. It was concluded
      that DCs in RA are highly activated and DC-initiated immune reaction may play an
      important role in the pathogenesis of RA. Simvastatin administration can
      significantly inhibit the DCs function and reduce the level of hs-CRP, indicating
      the suppression on inflammatory reaction may be one of the mechanisms by which
      simvastatin exerts its effect in treating RA.

PMID- 21181365
TI  - Clinicopathological analysis of central and extraventricular neurocytoma: a
      report of 17 cases.
AB  - Neurocytoma, a rare brain tumor, is characterized by a mass located mainly in
      cerebral ventricles. It is prone to be misdiagnosed as oligodendroglioma or
      ependymoma due to their similar histopathological features in clinical practice.
      This study aimed to examine the clinicopathological features and differential
      diagnosis of central and extraventricular neurocytoma. The clinical and
      histopathological data of 17 patients (male: female=7:10; age: 4-41 years; mean
      age: 27.4 years) with central or extraventricular neurocytoma were
      retrospectively analyzed. These patients showed typical radiological,
      histopathological and immunohistochemical features of neurocytoma. The tumor
      tissue was found to be composed of small uniform cells with round nuclei and
      clear cytoplasm resembling that of oligodendroglioma and ependymoma.
      Immunohistochemistry revealed the tumor tissues were positive for neuronal
      markers such as synaptophysin (SYN) and neuronal nuclear antigen (NeuN). It was
      concluded histopathological features of neurocytoma overlaps with some tumors in
      the central neural system. Immunopositivity for SYN and NeuN can help
      differentially diagnose neurocytoma.

PMID- 21181366
TI  - Proliferation characteristics of CD133+ cell population in colorectal cancer.
AB  - In this study, CD133+ subpopulations were isolated from 41 primary colorectal
      cancer tissues, the proliferation and cell cycle distribution of the cells were
      examined without in vitro expansion, and then compared to those of cell lines.
      The detection of CD133 in colorectal cancer tissues, isolation of CD133+ and
      CD133- epithelial subpopulations, Ki-67/DNA multiparameter assay and cell volume
      analysis were flow cytometrically conducted. The results showed that Ki-67
      expression was correlated with CD133 level in primary cancer tissues, while cell
      cycle G2/M phase distribution or clinicopathological characteristics was not. In
      addition, the CD133+ cells showed larger cell volume and higher Ki-67 expression
      as compared with CD133- cells. But there was no statistically significant
      difference in G(2)/M phase distribution between the two subpopulations. Our
      results demonstrated that the CD133+ subpopulation in colorectal cancer tissue
      contained more actively cycling and proliferating cells, which was not correlated
      to clinicopathological factors but might contribute to tumor progression and poor
      clinical outcome.

PMID- 21181367
TI  - Inhibitory effects of TNP-470 in combination with BCNU on tumor growth of human
      glioblastoma xenografts.
AB  - This study investigated the effect of TNP-470 in combination with carmustine
      (BCNU) on the growth of subcutaneously implanted human glioblastoma xenografts in
      nude mice. Human glioblastoma U-251 cells (1*10(7)) were injected into 24 nude
      mice subcutaneously. The tumor-bearing mice were randomly divided into 4 groups
      on the seventh day following tumor implantation: TNP-470 group, in which TNP-470
      was given 30 mg/kg subcutaneously every other day 7 times; BCNU group, in which
      20 mg/kg BCNU were injected into peritoneal cavity per 4 days 3 times; TNP-470
      plus BCNU group, in which TNP-470 and BCNU were coadministered in the same manner
      as in the TNP-470 group and the BCNU group; control group, in which the mice were
      given 0.2 mL of the mixture including 3% ethanol, 5% acacia and 0.9% saline
      subcutaneously every other day 7 times. The tumor size and weights were measured.
      The tumor microvessel density (MVD) was determined by immunostaining by using
      goat-anti-mouse polyclonal antibody CD105. The results showed that on the 21th
      day following treatment, the volume of xenografts in the TNP-470 plus BCNU group
      was (108.93+/-17.63)mm(3), markedly lower than that in the TNP-470 group
      [(576.10+/-114.29)mm(3)] and the BCNU group [(473.01+/-48.04)mm(3)] (both
      P<0.01). And the xenograft volume in these 3 treatment groups was even much lower
      than that in the control group [(1512.61+/-470.25) mm(3)] (all P<0.01). There was
      no significant difference in the volume of xenografts between the TNP-470 group
      and the BCNU group (P>0.05). The inhibition rate of the tumor growth in the TNP
      470 plus BCNU group was (92.80+/-11.37)%, notably higher than that in the TNP-470
      group [(61.91+/-6.29)%] and the BCNU group [(68.73+/-9.65)%] (both P<0.01) on the
      21th day following treatment. There was no significant difference in the
      inhibition rate of tumor growth between the TNP-470 group and the BCNU group
      (P>0.05). The MVD of xenografts in the TNP-470 plus BCNU group was decreased
      significantly as compared with that in the TNP-470 group or the BCNU group (both
      P<0.05). The MVD of xenografts in the 3 treatment groups was markedly reduced as
      compared with that in the control group (all P<0.05). No significant changes in
      weights were observed before and after the treatment in each group (all P>0.05).
      It was concluded that the combination of TNP-470 and BCNU can significantly
      inhibit the growth of human glioblastoma xenografts in nude mice without evident
      side effects.

PMID- 21181368
TI  - Clinical classification and treatment strategy of hamate hook fracture.
AB  - To explore the clinical classification of hamate hook fracture and the treatment
      strategy for different type of fractures, 12 patients who suffered from hamate
      hook fractures were followed up retrospectively. According to the fracture sites
      and the prognosis, we classified the hamate hook fractures into 3 types. Type I
      referred to an avulsion fracture at the tip of hamate hook, type II was a
      fracture in the middle part of hamate hook, and type III represented a fracture
      at the base of hamate hook. By the classification, in our series, only 1 fell
      into type I, 7 type II, and 4 type III. The results were evaluated with respect
      to the functional recovery, recovery time and the association among the clinical
      classification, pre-operative complications and treatment results. The average
      follow-up time of this group was 8.4+/-3.9 months. Two cases were found to have
      fracture non-union and both of them were type II fractures. Six patients had
      complications before operation. Five cases were type II fractures and 1 case type
      III fracture. All the patients were satisfied with the results at the time of the
      last follow-up. Their pain scale and grip strength improved significantly after
      treatment. All the pre-operative complications were relieved. The recovery time
      of hamate hook excision was significantly shorter than that of the other two
      treatments. The incidences of both pre-operative complications and non-union in
      type II fractures were higher than those in type I and type III fractures. It was
      concluded that, generally, the treatment effects with hamate hook fracture are
      quite good. The complication incidence and prognosis of the fracture are closely
      related to the clinical classification. Early intervention is critical for type
      II fractures.

PMID- 21181369
TI  - Effect of lipoxin A4 on IL-1beta production of monocytes and its possible
      mechanism in severe preeclampsia.
AB  - This study examined in vitro effect of lipoxin A(4) (LXA(4)) on interleukin-1beta
      (IL-1beta) production of monocytes and its possible mechanism in severe
      preeclampsia (PE). Peripheral venous blood was drawn from 15 patients with severe
      preeclampsia (PE group) and 20 normal pregnant women (control group) to prepare
      monocytes which were then treated with LXA(4) at different concentrations of 0,
      10, 100 nmol/L respectively. IL-1beta level in the supernatant of monocytes was
      detected by enzyme linked immunoassay. The [Ca(2+)](i) of monocytes was measured
      by laser scanning confocal microscopy. The results showed that the IL-1beta level
      and the [Ca(2+)](i) of monocytes in the PE group were significantly higher than
      those in the control group. LXA(4) significantly decreased the generation of IL
      1beta in a dose-dependent manner in the PE group. After treatment with 100-nmol/L
      LXA(4), in the PE group, the [Ca(2+)](i) concentration of monocytes was
      significantly reduced. It was concluded that LXA(4) may inhibit the IL-1beta
      production of monocytes from severe preeclampsia women by inhibiting
      extracellular calcium influx.

PMID- 21181370
TI  - Expression and biological function of N-myc down-regulated gene 1 in human
      cervical cancer.
AB  - The expression of N-myc down-regulated gene 1 (NDRG1) has previously been
      reported to be involved in the proliferation, differentiation, invasion and
      metastasis of cancer cells, but its role in cervical cancer is still unclear.
      This study aimed to investigate the expression of NDRG1gene in human cervical
      cancer and its effect on aggressive tumor behaviors. The NDRG1 expression in
      cervical tissues and cells was detected by RT-PCR. Specific expression plasmid
      pEGFP-N1-NDRG1-GFP was used to enhance the expression of NDRG1 in human cervical
      cancer cell lines. The mRNA and protein level of NDRG1 was assessed by RT-PCR and
      Western blotting, respectively. Its effects on cell proliferation, migration,
      invasion, cell cycle and apoptosis were detected by MTT, transwell migration
      assay and flow cytometry (FCM), respectively. The results showed that the
      expression of NDRG1 in cervical cancer tissues and cells was significantly lower
      than in normal cervical tissues (P<0.001). After transfection with pEGFP-N1-NDRG1
      GFP, the mRNA and protein expression of NDRG1 was up-regulated in Siha cells,
      which suppressed cell proliferation (P<0.001), induced cell cycle arrest
      (P<0.05), reduced invasion and migration of Siha cells (P<0.05), but caused no
      cell apoptosis. Moreover, vascular endothelial growth factor (VEGF), a tumor
      induced angiogenesis factor, was markedly reduced and E-cadherin, a cell adhesion
      molecule, was increased in the cells transfected with pEGFP-N1-NDRG1-GFP. It was
      concluded that up-regulated NDRG1 may play a role in the suppression of malignant
      cell growth, invasion and metastasis of human cervical cancer.

PMID- 21181371
TI  - Von Willebrand factor antigen and ADAMTS13 activity assay in pregnant women and
      severe preeclamptic patients.
AB  - The present study examined von Willebrand factor (vWF) levels and ADAMTS13
      activity in pregnant and severe preeclamptic women in order to shed light on the
      prothrombotic state in severe preeclampsia. Thirty healthy women of childbearing
      age, 22 second trimester pregnant women, 30 third trimester pregnant women and 10
      severe preeclamptic patients were recruited in this study. ADAMTS13 activity was
      determined by the FRETS-vWF73 assay and vWF antigen (vWF:Ag) levels by an enzyme
      linked immunosorbent assay. The results showed that there were statistically
      significant differences in plasma vWF antigen levels between the severe
      preeclamptic and third trimester pregnant women, between third and second
      trimester pregnant women (P<0.05). The third trimester pregnant women had
      significantly lower plasma ADAMTS13 activity than second trimester pregnant women
      (P<0.05). Nevertheless, no significant differences in plasma ADAMTS13 activity
      were found between severe preeclamptic patients and the third trimester pregnant
      women (P>0.05). In conclusion, plasma ADAMTS13 activity is normal in severe
      preeclampsia despite the increased vWF:Ag levels. Prothrombotic state is involved
      in the pathogenesis of severe preeclampsia, as a result of endothelial injury.

PMID- 21181372
TI  - The role of brain-derived neurotrophic factor in mouse oocyte maturation in
      vitro.
AB  - Brain-derived neurotrophic factor (BDNF) can promote developmental competence in
      mammalian oocytes during in vitro maturation (IVM), but the role of BDNF in
      oocyte maturation at cellular level is not still clear. In this study, mouse
      cumulus-enclosed oocytes subjected to IVM were fertilized and cultured to
      blastocyst stage. Meiotic spindle configuration and cortical granules
      distribution during oocyte maturation in vitro were assessed by using
      immunofluorescence and laser confocal microscopy. The results showed that BDNF
      contributed to the complete preimplantation development of mouse oocytes compared
      to the control oocytes (13.78% vs. 5.92%; P<0.05). Further, BDNF did not
      accelerate nuclear maturation of IVM oocytes. For the BDNF-treated oocytes at
      meiosis I, Meiotic spindle areas were significantly smaller and the number of
      cytoplasmic microtubule organizing centers was greater than that in the control,
      and the percentages of oocytes showed spindles positioned near the oolemma and a
      well-formed cortical granule-free domain were significantly higher than that of
      the control. These morphological characteristics of the BDNF-treated oocytes were
      much closer to the oocytes matured in vivo than those of the control oocytes. In
      conclusion, BDNF can promote the developmental competence of mouse IVM oocytes,
      by improving the meiotic spindle configuration and location and cortical granules
      distribution at meiosis 1.

PMID- 21181373
TI  - Identification of a novel dynamic red blindness in human by event-related brain
      potentials.
AB  - Dynamic color is an important carrier that takes information in some special
      occupations. However, up to the present, there are no available and objective
      tests to evaluate dynamic color processing. To investigate the characteristics of
      dynamic color processing, we adopted two patterns of visual stimulus called
      "onset-offset" which reflected static color stimuli and "sustained moving"
      without abrupt mode which reflected dynamic color stimuli to evoke event-related
      brain potentials (ERPs) in primary color amblyopia patients (abnormal group) and
      subjects with normal color recognition ability (normal group). ERPs were recorded
      by Neuroscan system. The results showed that in the normal group, ERPs in
      response to the dynamic red stimulus showed frontal positive amplitudes with a
      latency of about 180 ms, a negative peak at about 240 ms and a peak latency of
      the late positive potential (LPP) in a time window between 290 and 580 ms. In the
      abnormal group, ERPs in response to the dynamic red stimulus were fully lost and
      characterized by vanished amplitudes between 0 and 800 ms. No significant
      difference was noted in ERPs in response to the dynamic green and blue stimulus
      between the two groups (P>0.05). ERPs of the two groups in response to the static
      red, green and blue stimulus were not much different, showing a transient
      negative peak at about 170 ms and a peak latency of LPP in a time window between
      350 and 650 ms. Our results first revealed that some subjects who were not
      identified as color blindness under static color recognition could not completely
      apperceive a sort of dynamic red stimulus by ERPs, which was called "dynamic red
      blindness". Furthermore, these results also indicated that low-frequency ERPs
      induced by "sustained moving" may be a good and new method to test dynamic color
      perception competence.

PMID- 21181374
TI  - Molecular genetic analysis of autosomal dominant late-onset cataract in a Chinese
      Family.
AB  - Congenital cataract is a highly heterogeneous disorder at both the genetic and
      the clinical-phenotypic levels. A unique cataract was observed in a 4-generation
      Chinese family, which was characterized by autosomal dominant inheritance and
      late-onset. Mutations in the 13 known genes (CRYAA, CRYAB, CRYBB1, CRYBB2, CRYGC,
      CRYBA1/A3, CRYGD, Connexin50, Connexin46, intrinsic membrane protein LIM2,
      cytoskeletal protein BFSP2, the major intrinsic protein-MIP and the heat shock
      factor HSF4) have previously been demonstrated to be the frequent reason for
      isolated congenital cataracts, but the exact molecular basis and underlying
      mechanisms of congenital cataract still remain unclear. This study was designed
      to find whether these 13 genes developed any mutation in the family members and
      to identify the disease-causing gene. Polymerase chain reaction (PCR) and direct
      DNA sequence analysis were carried out to detect the 13 genes. The results showed
      that no mutation causing amino acid alternations was found in these potential
      candidate genes among all patients in the family, and only several single
      nucleotide polymorphisms (SNPs) were identified. A transitional mutation in the
      fourth intron of CRYBB2 and some silent mutations in the first exon of BFSP2 and
      CRYGD were found in the cataract family, but further study showed that these
      mutations could also be found in normal controls. It was concluded that some
      unidentified genes may underlie the occurrence of late-onset cataract in this
      family. A genome-wide screening will be carried out in the next study.

PMID- 21181375
TI  - Targeting therapy of choroidal neovascularization by use of polypeptide- and PEDF
      loaded immunoliposomes under ultrasound exposure.
AB  - Pigment epithelium derived factor (PEDF) has been proven to be an effective drug
      for the treatment of choroidal neovascularization (CNV). However, the lack of
      ideal administration route is the biggest bottleneck preventing PEDF from wider
      clinical use. In this study, we developed a novel PEDF-carrying system which
      employed immuno-nano-liposomes (INLs) under ultrasound exposure. PEDF-loaded INLs
      were prepared by conjugating nanoliposomes to the peptide ATWLPPR specifically
      targeting the receptor-2 for vascular endothelial growth factor (VEGFR-2) and
      reversely encapsuling PEDF. RF/6A cells were incubated with PEDF-loaded INLs. CNV
      models of BN rats were injected with PEDF-loaded INLs. MTT assay was used to
      evaluate the cytotoxicity of the INLs on RF/6A cells. Flow cytometry was
      conducted to detect the apoptotic rate of cells. Laser scanning confocal
      microscopy was employed to observe the binding and transmitting process of PEDF
      loaded INLs and to calculate the area of CNV in the rat model. The results showed
      that the PEDF-loaded INLs could exclusively bind to CNV but not to the normal
      choroidal vessels. The CNV area was significantly decreased in PEDF treatment
      groups in comparison with control group (P<0.05). Moreover, PEDF-loaded INLs
      exposed under ultrasound were more efficient in reducing the CNV area (P<0.05).
      It was concluded that INLs in combination with ultrasonic exposure can transmit
      PEDF into cytoplasma with high specificity and efficiency, which strengthens the
      inhibitory effects of PEDF on CNV and reduces its side effects. PEDF-loaded INLs
      possibly represent a new treatment paradigm for patients with ocular
      neovascularization.

PMID- 21181376
TI  - Corneal permeability assay of topical eye drop solutions in rabbits by MRI.
AB  - This study examined the corneal permeability of topical eye drop solutions added
      with various corneal penetrating accelerators and gadolinium-diethylene triamine
      pentaacetic acid (Gd-DTPA) by nuclear magnetic resonance imaging (MRI). Twenty
      four New Zealand rabbits were randomly divided into 3 groups according to the
      random digits table: Gd-DTPA group, in which the rabbits received 23.45% Gd-DTPA;
      hyaluronic acid group, in which 23.45% Gd-DTPA plus 0.2% hyaluronic acid was
      administered; azone group, in which 23.45% Gd-DTPA with 0.2% azone was given.
      Fifty microliters of the eye drops was instilled into the conjunctive sac every 5
      min, for a total of 6 applications in each group. Contrast medium signals in the
      cornea, anterior chamber, posterior chamber, and vitreous body were scanned
      successively by MRI. The morphology and cell density of the corneal endothelium
      were examined before and 24 h after the treatment. The results showed that the
      residence time of Gd-DTPA in the conjunctival sac in the hyaluronic acid and
      azone groups was longer than that in the Gd-DTPA group. The signals in the
      anterior chamber of the Gd-DTPA and hyaluronic acid groups were increased
      slightly, and those in the azone group strengthened sharply. The signal intensity
      continuously rose over 80 min before reaching plateau. The strengthening rate of
      signals in the anterior chamber was 19.63% in the Gd-DTPA group, 53.42% in the
      sodium hyaluronate group, and 226.94% in the azone group. No signal was detected
      in the posterior chamber or vitreous body in all the 3 groups. Corneal morphology
      and cell density did not show any significant changes after the treatment in all
      the 3 groups. It was concluded that azone can significantly improve the corneal
      permeability of drugs that are similar to Gd-DTPA in molecular weight and
      molecular size, and MRI is a noninvasive technique that can dynamically detect
      eye drop metabolism in real time.

PMID- 21181377
TI  - Inhibitory effect of PPARgamma agonist on the proliferation of human pterygium
      fibroblasts.
AB  - The effects of DK2, a peroxisome proliferator-activated receptor gamma agonist,
      on cultured human pterygium fibroblasts (HPFs) in virto were studied. The HPFs
      were incubated with 0-200 MUmol/L DK2 for 12-72 h. The MTT method was used to
      assay the bio-activity of DK2 at different doses and time. The cytotoxic effect
      of DK2 was measured by LDH release assay. The cell cycle distribution and
      apoptosis were flow cytometrically detected. The expression of proliferating cell
      nuclear antigen (PCNA) in each group was detected by real-time PCR (RT-PCR) and
      Western blotting. The results showed that administration of 1-75 MUmol/L DK2 for
      12-72 h could significantly inhibit HPF proliferation in a dose- and time
      dependent manner. DK2-treated cells did not release significant amount of LDH as
      compared with rosiglitazone-treated cells. After treatment with DK2 at
      concentrations of 15, 25 MUmol/L for 24 h, the number of HPFs in G(0)/G(1) phase
      was significantly increased while that in S phase was significantly decreased
      (P<0.05), leading to arrest at G(0)/G(1) phase. The apoptosis rates of HPF cells
      in drug-treated groups were significantly higher than the rate of control group
      (P<0.05). At the dosage range between 15-25 MUmol/L, DK2 could inhibit the
      expression of PCNA mRNA and protein in HPFs in a dose-dependent fashion (P<0.05).
      It was concluded that PPARgamma agonist can significantly inhibit HPF
      proliferation, resulting in the arrest at G(0)/G(1) phase, induce the apoptosis
      of HPFs, and suppress the synthesis of PCNA, in dose- and time-dependent manners.

PMID- 21181378
TI  - Correlation between calcified liver metastases and histopathology of primary
      colorectal carcinoma in Chinese.
AB  - The study examined the association between calcified liver metastases and the
      histopathology of the primary colorectal carcinoma in Chinese. The clinical,
      pathological and CT data were retrospectively analyzed in 210 patients (mean age:
      54.2 years) with liver metastases from colorectal carcinoma. Plain CT scanning
      and contrast-enhanced scanning were performed in all the patients. For the
      contrast-enhanced examination, iohexol was injected by using a high pressure
      syringe at a flow rate of 2.5-3.0 mL/s. The arterial phase lasted approximately
      25 s and the portal venous phase about 60 s. All patients had no history of
      chronic liver diseases and had never received interventional treatments. chi(2)
      test was used to analyze the rate of calcification in the liver metastasis from
      colorectal cancer of different differentiation degrees. Among the 210 cases of
      liver metastases, 22 patients (10.5%) were found to have calcified liver
      metastases on CT scan. Two patients with calcified liver metastasis received
      lumpectomy and developed calcification in recurrent tumors. Another two patients
      had calcification in newly developed tumor masses. And the calcification in the
      newly developed masses was similar to that of their primary counterparts in terms
      of morphology and distribution. On the enhanced CT scan, the tumors exhibited no
      enhancement during hepatic arterial phase and showed slight rim enhancement
      during portal venous scan in the 22 cases. The calcification became obscure on
      contrast-enhanced scans. Histopathologically, the primary tumors were well
      differentiated adenocarcinoma in 6 cases, moderately-differentiated
      adenocarcinoma in 10, poorly-differentiated adenocarcinoma in 4 and mucinous
      adenocarcinoma in 2 among the 22 cases. No statistical correlation was noted
      between the incidence of calcified liver metastasis and the pathological subtypes
      and differentiation degrees of the primary colorectal carcinoma. It was concluded
      that calcified liver metastases may result from colorectal adenocarcinomata of
      different differentiation degrees or mucinous adenocarcinomata in Chinese
      population. There is no correlation between calcification of liver metastases and
      the pathological subtype of the primary colorectal carcinoma in Chinese, which is
      different from the findings that calcified metastases were associated with
      colorectal mucinous adenocarcinoma in other ethnic groups.

PMID- 21181379
TI  - Assessment of left atrial function in diabetes mellitus by left atrial volume
      tracking method.
AB  - The value of the left atrial volume tracking (LAVT) method in the evaluation of
      left atrial (LA) function in patients with diabetes mellitus (DM) was examined in
      this study. Fifty-eight DM patients as DM group and 40 healthy people as normal
      control group were enrolled in this study. EUB-6500 echocardiographic imaging
      system with LAVT was applied to display and analyze the LA volume curve imaging
      on LV apical two and four chamber views. The maximal LA volume at end-systole
      (LAV(max)), LA volume at the onset of ECG-P wave (LAV(p)), the minimal LA volume
      at end-diastole (LAV(min)) from the LA volume curve were acquired and recorded.
      All values above were standardized by body surface area (BSA). Then the passive,
      active and total LA volume (LAVIpass, LAVIact, LAVItotal) and empting rate
      (%LAVIpass, %LAVIact, %LAVItotal), effective passive and active empting rate
      (%eLAVIpass, %eLAVIact), and the proportionality of passive empting volume and
      active empting volume were calculated. The LAVIp, LAVIact, LAVItotal, %LAVIact,
      %LAVItotal and %eLAVIact were significantly higher in the DM group than those in
      the control group, whereas the LAVIpass, %LAVIpass, %eLAVIpass and LAVIpass/act
      were lower (all P<0.05). For the LA volume change in DM, the active empting
      volume was enhanced at end-diastole. It was concluded that LAVT is a potentially
      useful tool to evaluate the function of LA.

PMID- 21181380
TI  - Hepatofugal portal flow associated with acute rejection in living-donor auxiliary
      partial orthotopic liver transplantation: a report of one case and literature
      review.
AB  - We report a case of reversible hepatofugal portal flow after auxiliary partial
      orthotopic liver transplantation (APOLT) from a living donor in this study. On
      postoperative day 6, continuous hepatofugal portal flow was observed in the
      grafted liver without portal thrombosis and obstruction of the hepatic vein.
      Based on histological findings, acute rejection was the suspected cause. The
      normal portal venous flow was restored after steroid pulse and antithymocyte
      globulin (ATG) therapies. The patient was discharged on the 30th postoperative
      day. It was concluded that hepatofugal flow after liver transplantation is a sign
      of serious acute rejection, and can be successfully treated by anti-rejection
      therapy.

PMID- 21181381
TI  - [Fitting hearing aids without an ENT physician?: three case reports].
AB  - Fitting hearing aids without primary diagnosis by an ENT physician can be
      dangerous for the patient in so far as serious disease may be overlooked. Three
      case reports are presented where acoustic neurinoma, psychogenic hearing loss and
      sudden rupture of the round window with subsequent perilymphatic fistula were the
      actual causes of hearing loss.

PMID- 21181382
TI  - [Clinical experiences with an automatic collision warning system: instrument
      navigation in endoscopic transnasal surgery].
AB  - PROBLEM: The goal of this work is the extension of instrument navigation with a
      collision warning function. With the help of an additional distance display and
      warning system the performance of surgical navigation systems should be improved.
      MATERIAL AND METHODS: The collision warning system (DCS) is an extension of an
      optoelectric navigation system (NPU, Karl Storz GmbH&Co.KG, Tuttlingen, Germany).
      The measurement of situation awareness was performed on phantom models of
      functional endoscopic surgery of the paranasal sinuses (FESS; Phacon, Leipzig).
      Altogether 450 measurement pairs for the analysis of surgical accuracy to the
      risk structure (frontal skull base, lamina papyracea, internal carotid artery)
      were available. To examine the influence on the clinical process, a prospective
      analysis of intraoperative complications was carried out. Of the 104 FESS
      patients, two groups, one of 56 patients with only navigation (NAV) and one of 48
      patients (NAV+DCS), were examined. Efficiency was evaluated on the basis of times
      for system preparation and intraoperative application. RESULTS: A significant
      increase in the assumed and actual distance values between instrument tip and
      risk structure using the collision warning system was seen at 76%. The
      complication rate was more favorable for the NAV+DCS group. The time needed for
      preparation of the navigation system with the application of the collision
      warning system increased on average by 48%, or 1.2 min. However, the relation
      between preparation time and utilization time was approximately the same at 53.5%
      in the NAV group and 57.4% in the NAV+DCS group. CONCLUSIONS: This work supports
      the clinical use and efficiency of a collision warning system as an addition to
      well-known instrument navigation in endo- and transnasal surgery. The segmenting
      algorithm is suitable for clinical requirements.

PMID- 21181383
TI  - [Pattern generators and more. Cortical control mechanisms of swallowing].
AB  - BACKGROUND: Swallowing as a neurophysiological process has recently attracted
      much interest. Knowledge of cortical involvement in particular has raised hope
      that a novel form of dysphagia therapy might be possible by means of cortical
      stimulation. METHOD: For this systematic review a selective literature research
      in PubMed has been carried out. RESULTS: The cortex is not only involved in the
      initiation of swallowing, but also during pharyngeal and esophageal phases. In
      addition, there appears to be a hemispheric dominance both for swallowing and its
      individual phases. DISCUSSION: In light of recent study results, the theory of
      the pattern generators' autonomy must be abandoned, since pattern generators seem
      to be influenced rather by the cortex. During the recovery of unilateral
      impairments, the intact hemisphere seems to play a significant role due to
      cortical reorganisation processes. Several studies indicate that repetitive
      transcranial stimulation, and thereby modulation of cortical areas as a means of
      dysphagia therapy, could be beneficial.

PMID- 21181384
TI  - [Influence of expansions on grammar acquisition in children with cochlear
      implants].
AB  - BACKGROUND: It was investigated whether expansions ("corrective feedback"), a
      feature of the language adults direct at young children, have an influence on the
      acquisition of grammar in children with cochlear implants (CI). MATERIALS AND
      METHODS: Participants of the longitudinal study included 21 children with CI and
      their mothers. The age of implantation was between 14 and 46 months. In the
      spontaneous speech between mother and child, plurals, verb markings, copula and
      articles were measured. The expansion of a grammatical form was correlated with
      the child's use of the same form at a later point in time (time-lagged
      correlations). RESULTS: Significant positive correlations were found between the
      expansion of a grammatical form and the child's usage. This was the case for all
      morphemes analyzed. Correlations ranged between r=0.42 and r=0.70 (p<0.05 and
      p<0.01). CONCLUSION: Results indicate that parental language directed at children
      with CI can have a specific effect on the child's acquisition of grammatical
      forms. The outcome of this study has an impact on parent counselling, early
      intervention programmes and CI rehabilitation.

PMID- 21181385
TI  - [Primary malignant melanoma arising from the base of the tongue: a case report].
AB  - Primary mucosal melanoma is a biologically aggressive neoplasm, which is rarely
      located at the base of the tongue. The absence of early signs and symptoms, the
      lack of an evidence-based treatment, the early development of metastases and high
      rates of local recurrence contribute to the overall poor prognosis of these
      melanomas. This paper reports the case of a 66-year-old male presenting with
      local recurrence of a primary melanoma of the base of the tongue.

PMID- 21181386
TI  - [Drooling following radiation. Botulinum toxin as a successful treatment
      modality].
AB  - Drooling is both a clinical sign for the diminished control of saliva and oral
      motor function and a heavy social burden for patients. We report a case in which
      drooling deteriorated after radiotherapy of the head and neck region as the
      primary treatment for hypopharyngeal cancer, although radiotherapy of the
      salivary glands is known to be an effective treatment option for drooling. In
      this particular case, injection of botulinum toxin in the parotid and
      submandibular glands significantly reduced drooling. The excellent response to
      botulinum toxin is of great clinical interest for similar RT non-responders.

PMID- 21181387
TI  - [Fool's gold standards in language screening. Sensitivity and specificity of the
      Hessian child language screening test (Kindersprachscreening, KiSS)].
AB  - BACKGROUND: The German Kindersprachscreening (KiSS) is a universal speech and
      language screening test for large-scale identification of Hessian kindergarten
      children requiring special educational language training or clinical
      speech/language therapy. PARTICIPANTS AND METHODS: To calculate the procedural
      screening validity, 257 children (aged 4.0 to 4.5 years) were tested using KiSS
      and four language tests (Reynell Development Language Scales III,
      Patholinguistische Diagnostik, PLAKSS, AWST-R). The majority or consensus
      judgements of three speech-language professionals, based on the language test
      results, served as a reference criterion. The base (fail) rates of the
      professionals were either self-determined or preset based on known prevalence
      rates. RESULTS: Screening validity was higher for preset than for self-determined
      base rates due to higher inter-judge agreement. The confusion matrices of the
      overall index classification of the KiSS (speech-language abnormalities with
      educational or clinical needs) with the fixed base rate expert judgement about
      language impairment, including fluency or voice disorders, yielded a sensitivity
      of 88% and a specificity of 78%, for just language impairment 84% and 75%,
      respectively. Specificities for disorders requiring clinical diagnostics in the
      KiSS (language impairment alone or combined with fluency/voice disorders) related
      to the test-based consensus expert judgment was about 93%. Sensitivities were
      unsatisfactory because the differentiation between educational and clinical needs
      requires improvement. CONCLUSION: Since the judgement concordances between the
      speech-language professionals was only moderate, the development of a
      comprehensive German reference test for speech and language disorders with
      evidence-based algorithmic decision rules rather than subjective clinical
      judgement is advocated.

PMID- 21181388
TI  - [Tumour of the endolymphatic sac in a 12-year-old child].
AB  - We present the case of a 12-year-old boy with right-sided pantonal sensorineural
      hearing loss. With the help of imaging diagnostics a tumour of the right temporal
      bone was detected. It was resected using a transmastoid approach.
      Histopathological study showed a low-grade adenocarcinoma of the endolymphatic
      sac, known as Heffner tumour. An association with the von-Hippel-Lindau complex -
      as often reported in the medical literature - could not be proven.

PMID- 21181389
TI  - [Laryngeal MALT lymphoma with known Sjogren syndrome].
AB  - Hematopoietic neoplasms represent about 1% of all laryngeal neoplasms. MALT
      lymphoma arises from mucosa-associated lymphoid tissue and is associated with
      chronic inflammatory disease. Patients with Sjogren syndrome have a higher risk
      for development of non-Hodgkin lymphoma (MALT lymphoma). To date, only cases of
      MALT lymphoma of the salivary glands, thymus and stomach associated with Sjogren
      syndrome have been published. We present the case of a MALT lymphoma of the
      larynx associated with Sjogren syndrome. Radiation and chemotherapy are the first
      line of therapy as published in the literature.

PMID- 21181390
TI  - [Microarray technique for component resolved diagnosis (CRD) in type-I allergies.
      An innovative technology at the border between research tool and routine
      diagnostics].
AB  - Approximately 25% of the population in industrialized countries suffer from IgE
      associated Type-1 allergies. Multiple allergens can be tested simultaneously in
      one assay by using the protein microarray. Moreover, it is possible to measure
      more than one analytical parameter (e.g. allergen specific IgEs and IgGs) in one
      assay by combining different fluorescent markers with specific secondary
      antibodies. The different allergen components that are of interest are
      immobilized on a planar surface. By adding the patient's serum (a smaller amount
      of serum is needed compared to an immunoassay) the inherent IgE antibodies are
      captured by the corresponding allergens. Secondary fluorescing anti-IgE
      antibodies are added subsequently, thus the intensity of each spot on the
      microarray can be measured by using a biochipscanner. The detected signal is then
      transformed into quantitative data, which allows the classification of the
      patient's serum IgE level for the tested allergens. There are different
      approaches to reduce the complexity of the original extracts used for the
      production of the solid microarray phase to a smaller number of relevant
      pathogenic molecules. The component-resolved diagnosis still needs to be
      clinically validated, but initial studies show positive results concerning the
      sensitivity and specificity of the protein microarray. Protein microarrays are
      promising tools for screening diagnoses in allergic diseases as well as for the
      improvement of allergen-specific immunotherapy.

PMID- 21181391
TI  - [The incidence of Frey syndrome following parotidectomy: results of a survey and
      follow-up].
AB  - BACKGROUND: Frey's syndrome (FS) is defined as facial sweating due to gustatory
      stimuli following surgery or trauma of the parotid gland. Concomitant symptoms
      may occur in the area of the auriculotemporal nerve: swelling, facial flushing,
      and paresthesia. A misguided re-innervation of perspiratory glands by secretory
      parasympathetic fibres is likely responsible in the pathogenesis. The reported
      incidence in the literature varies considerably from 1.7% to 97.6%. The present
      study aims to clarify the incidence of FS. PATIENTS AND METHODS: A questionnaire
      was sent to 221 consecutive patients who underwent parotidectomy between 07/2005
      and 07/2008. No selection for type of parotidectomy or histological result was
      made. Patients were invited to undergo a follow-up examination including Minor's
      iodine starch test. RESULTS: A total of 135 of 221 (61%) questionnaires were
      available for evaluation. In all, 82 patients took part in the follow-up, with a
      follow-up period of 2.8 years (15-51 months). According to the questionnaire, 54%
      of patients claimed to be free of symptoms. Sweating following gustatory stimuli
      was reported by 23% of patients. Of the 82 Minor's tests performed, 62.2% were
      positive. All patients with subjective presence of FS had a positive Minor's
      test. In 27%, Minor's test was positive although patients did not suffer from
      facial sweating subjectively ("subclinical FS"). In all, 39% had no subjective
      complaints and Minor's test was also negative. Cases with a positive Minor's test
      showed no statistically significant relation to the patients' age, gender or to
      the histological diagnosis or type of parotidectomy. CONCLUSION: The clinical
      incidence of FS in our study is 23%, although a positive Minor's iodine starch
      test was observed in 62% of cases. Therefore, it seems justifiable to
      differentiate between a symptomatic or clinical FS and a merely asymptomatic or
      subclinical FS. No correlation was observed between epidemiological factors and
      the occurrence of FS.

PMID- 21181392
TI  - [Laryngectomised patients with voice prostheses: influence of supra-esophageal
      reflux on voice quality and quality of life].
AB  - INTRODUCTION: We conducted a prospective study to assess the influence of supra
      esophageal reflux on voice quality and quality of life in patients who had
      undergone laryngectomy and prosthetic voice rehabilitation. PATIENTS AND METHODS:
      We investigated 60 laryngectomised patients using 24-h dual-probe pH monitoring
      before and 6 months after oral anti-reflux treatment with proton pump inhibitors
      (PPIs). Quality of life was assessed using the European Organisation for Research
      and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30. Voice
      quality was quantified using the voice handicap index (VHI10). Quality of life
      and voice quality parameters were then correlated with the severity of reflux
      disease. RESULTS: Patients with physiological reflux area index (RAI) scores had
      a mean VHI10 score of 46.4 (+/-11.4). VHI scores were found to increase to up to
      64.1 (+/-9.6) with reflux severity (p=0.025). Total quality of life scores ranged
      from 115.8 (+/-24.7) in patients with physiological RAI scores to 131.0 (+/-33.1)
      in patients with highly pathological RAI scores (p=0.007). After 6 months of
      treatment with PPIs, VHI scores improved to a total score of 57.5 (+/-20.6,
      p=0.003). Quality of life scores improved to 123.3 (+/-29.0, p=0.045).
      CONCLUSION: Supra-esophageal reflux influences voice quality and quality of life
      in laryngectomised patients with voice prostheses. This can be explained, for
      example, by an increased incidence of periprosthetic leakage, the presence of
      edema in the pharyngo-esophageal segment (where speech is produced), and general
      reflux symptoms. Rigorous treatment with anti-reflux medications leads to an
      improvement in reflux parameters that can be assessed objectively (RAI) and in
      correlated quality of life and voice quality parameters. For this reason, we
      recommend rigorous oral treatment with PPIs in laryngectomised patients with a
      confirmed diagnosis of supra-esophageal reflux.

PMID- 21181393
TI  - [Sudden unilateral loss of vision under high-dosage corticosteroid therapy for
      pansinusitis].
AB  - Endogenous and exogenous glucocorticoids are suspected to play a key role in the
      development of central serous chorioretinopathy (CSC), which is characterized by
      a serous detachment of the neurosensory retina caused by the accumulation of
      fluid between the retinal pigment epithelium and the photoreceptor layer. We
      report the case of a patient with pansinusitis who was treated with high-dose
      corticosteroids and developed CSC. Patients under systemic corticosteroid therapy
      should be informed about the associated risk and symptoms of CSC.

PMID- 21181394
TI  - Intrahepatic and intramyocellular lipids are determinants of insulin resistance
      in prepubertal children.
AB  - AIMS/HYPOTHESIS: We hypothesised that ectopic fat deposition is present in liver
      and skeletal muscle before puberty and that both are potentially important
      factors in the early pathogenesis of insulin resistance. METHODS: Proton magnetic
      resonance spectroscopy was used to evaluate intramyocellular and intrahepatic
      lipids in 50 male and 42 female multi-ethnic, prepubertal (Tanner < 2) children
      (8.1 +/- 0.8 years; 35.4 +/- 10.7 kg; 27.9 +/- 8.3% body fat; means +/- SD).
      Intramyocellular lipid was measured in soleus muscle and intrahepatic lipid in
      the middle right lobe. Abdominal fat was measured by magnetic resonance imaging,
      body fat by dual energy X-ray absorptiometry, and insulin resistance using
      homeostatic model assessment. RESULTS: Intrahepatic lipid ranged from 0.11% to
      4.6% relative to the liver water signal (mean 0.79 +/- 0.79%) whereas
      intramyocellular lipid ranged from 0.13% to 1.86% relative to the muscle water
      signal (mean 0.51 +/- 0.28%). Intramyocellular and intrahepatic lipids were
      significantly correlated with total adiposity (r = 0.49 and 0.59), abdominal
      adiposity (r = 0.44 and 0.54), and each other (r = 0.39, p < 0.05, Spearman).
      Both intramyocellular and intrahepatic lipid were positively correlated with
      fasting insulin (r = 0.37 and 0.38 respectively) and insulin resistance (r = 0.37
      and 0.37; p < 0.01). After adjustment for race and sex, the relations between
      ectopic fat and insulin resistance remained, whereas both disappeared when
      further adjusted for body fat or BMI z scores. CONCLUSIONS/INTERPRETATIONS: These
      results suggest that typical relations between body composition, ectopic fat and
      insulin resistance are present in children before puberty. Thus, interventions
      aimed at reducing adiposity have the potential to decrease ectopic fat
      accumulation, delay the onset of insulin resistance and decrease the risk for
      development of type 2 diabetes in children.

PMID- 21181395
TI  - Decreased glucose tolerance and plasma adiponectin:resistin ratio in a mouse
      model of post-traumatic stress disorder.
AB  - AIMS/HYPOTHESIS: Obesity and type 2 diabetes are among the most serious health
      pathologies worldwide. Stress has been proposed as a factor contributing to the
      development of these health risk factors; however, the underlying mechanisms that
      link stress to obesity and diabetes need to be further clarified. Here, we study
      in mice how chronic stress affects dietary consumption and how that relationship
      contributes to obesity and diabetes. METHODS: C57BL/6J mice were subjected to
      chronic variable stress (CVS) for 15 days and subsequently fed with a standard
      chow or high-fat diet. Food intake, body weight, respiratory quotient, energy
      expenditure and spontaneous physical activity were measured with a customised
      calorimetric system and body composition was measured with nuclear magnetic
      resonance. A glucose tolerance test was also applied and blood glucose levels
      were measured with a glucometer. Plasma levels of adiponectin and resistin were
      measured using Lincoplex kits. RESULTS: Mice under CVS and fed with a high-fat
      diet showed impaired glucose tolerance associated with low plasma
      adiponectin:resistin ratios. CONCLUSIONS/INTERPRETATION: This study demonstrates,
      in a novel mouse model, how post-traumatic stress disorder enhances vulnerability
      for impaired glucose metabolism in an energy-rich environment and proposes a
      potential adipokine-based mechanism.

PMID- 21181396
TI  - Per-arnt-sim (PAS) domain-containing protein kinase is downregulated in human
      islets in type 2 diabetes and regulates glucagon secretion.
AB  - AIMS/HYPOTHESIS: We assessed whether per-arnt-sim (PAS) domain-containing protein
      kinase (PASK) is involved in the regulation of glucagon secretion. METHODS: mRNA
      levels were measured in islets by quantitative PCR and in pancreatic beta cells
      obtained by laser capture microdissection. Glucose tolerance, plasma hormone
      levels and islet hormone secretion were analysed in C57BL/6 Pask homozygote
      knockout mice (Pask-/-) and control littermates. Alpha-TC1-9 cells, human islets
      or cultured E13.5 rat pancreatic epithelia were transduced with anti-Pask or
      control small interfering RNAs, or with adenoviruses encoding enhanced green
      fluorescent protein or PASK. RESULTS: PASK expression was significantly lower in
      islets from human type 2 diabetic than control participants. PASK mRNA was
      present in alpha and beta cells from mouse islets. In Pask-/- mice, fasted blood
      glucose and plasma glucagon levels were 25 +/- 5% and 50 +/- 8% (mean +/- SE)
      higher, respectively, than in control mice. At inhibitory glucose concentrations
      (10 mmol/l), islets from Pask-/- mice secreted 2.04 +/- 0.2-fold (p < 0.01) more
      glucagon and 2.63 +/- 0.3-fold (p < 0.01) less insulin than wild-type islets.
      Glucose failed to inhibit glucagon secretion from PASK-depleted alpha-TC1-9
      cells, whereas PASK overexpression inhibited glucagon secretion from these cells
      and human islets. Extracellular insulin (20 nmol/l) inhibited glucagon secretion
      from control and PASK-deficient alpha-TC1-9 cells. PASK-depleted alpha-TC1-9
      cells and pancreatic embryonic explants displayed increased expression of the
      preproglucagon (Gcg) and AMP-activated protein kinase (AMPK)-alpha2 (Prkaa2)
      genes, implying a possible role for AMPK-alpha2 downstream of PASK in the control
      of glucagon gene expression and release. CONCLUSIONS/INTERPRETATION: PASK is
      involved in the regulation of glucagon secretion by glucose and may be a useful
      target for the treatment of type 2 diabetes.

PMID- 21181397
TI  - Association of the C47T polymorphism in SOD2 with diabetes mellitus and diabetic
      microvascular complications: a meta-analysis.
AB  - AIMS/HYPOTHESIS: A meta-analysis was performed to assess the association of C47T
      (rs4880) (also called Val16Ala) polymorphism in SOD2 gene with reduced risk of
      diabetes mellitus, including type 1 and type 2 diabetes, and diabetic
      microvascular complications (DMI) including diabetic nephropathy, diabetic
      retinopathy and diabetic polyneuropathy. METHODS: A comprehensive search was
      conducted to identify all case-control or cohort design studies of the above
      mentioned associations. The fixed or random effect pooled measure was selected on
      the basis of homogeneity test among studies. Heterogeneity among studies was
      evaluated using the I (2). Meta-regression and the 'leave one out' sensitive
      analysis of Patsopoulos et al. were used to explore potential sources of between
      study heterogeneity. Publication bias was estimated using modified Egger's linear
      regression test as proposed by Harbord et al. RESULTS: Seventeen articles were
      included. After excluding articles that deviated from Hardy-Weinberg equilibrium
      in cases and/or in controls, and were also the key contributors to between-study
      heterogeneity, the meta-analysis showed a significant association of the C allele
      with reduced risk of DMI in dominant (OR 0.788, 95% CI 0.680-0.914), recessive
      (OR 0.808, 95% CI 0.685-0.953) and codominant (OR 0.828, 95% CI 0.751-0.913)
      models. It also showed a significant association with reduced risk of diabetic
      nephropathy in the dominant model (OR 0.801, 95% CI 0.664-0.967), and reduced
      risk of diabetic retinopathy in the dominant (OR 0.601, 95% CI 0.423-0.855),
      recessive (OR 0.548, 95% CI 0.369-0.814) and codominant (OR 0.651, 95% CI 0.517
      0.820) models. CONCLUSIONS/INTERPRETATION: The meta-analysis suggested that C
      allele of C47T polymorphism in SOD2 gene has protective effects on risk of DMI,
      diabetic nephropathy and diabetic retinopathy. This risk needs to be confirmed by
      further studies.

PMID- 21181398
TI  - Synergistic effects of genetic beta cell dysfunction and maternal glucose
      intolerance on offspring metabolic phenotype in mice.
AB  - AIMS/HYPOTHESIS: Diabetes in pregnancy is linked to development of obesity in the
      offspring, but the mechanisms are not fully understood. Gestational diabetes
      mellitus (GDM) occurs when beta cells are unable to compensate for the normal
      insulin resistance of late pregnancy. In this study, we used a murine model of
      beta cell dysfunction to examine the effects of maternal GDM on phenotype in male
      offspring with and without an inherited predisposition for beta cell dysfunction.
      METHODS: Beta cell-specific aryl-hydrocarbon receptor nuclear translocator-null
      (betaArnt) mice develop GDM from beta cell dysfunction. betaArnt and control
      female mice were used to induce GDM and non-diabetic pregnancies, respectively.
      RESULTS: Offspring from GDM pregnancies became spontaneously obese on a normal
      chow diet. They were heavier than offspring from non-diabetic pregnancies, with
      increased body fat. Respiratory exchange ratio (RER) was higher, indicating
      decreased capacity to switch to lipid oxidation. Metabolic rate in GDM offspring
      was decreased prior to onset of obesity. The phenotype was more pronounced in
      betaArnt GDM offspring than in GDM offspring of control genotype, demonstrating
      an interaction between genotype and pregnancy exposure. betaArnt GDM offspring
      had increased hypothalamic neuropeptide Y (Npy) and decreased pro
      opiomelanocortin (Pomc) expression. Weight, body fat, insulin sensitivity and RER
      in all mice, and hypothalamic Npy in betaArnt mice were significantly correlated
      with AUC of maternal late pregnancy glucose tolerance tests (p < 0.01), but not
      with litter size, maternal weight, triacylglycerol or pre-pregnancy glycaemia.
      CONCLUSIONS/INTERPRETATION: In betaArnt mice, exposure to GDM and inheritance of
      genetic beta cell dysfunction had additive effects on male offspring obesity;
      severity of the offspring phenotype correlated with maternal glycaemia.

PMID- 21181400
TI  - Increased fracture risk in normocalcemic postmenopausal women with high
      parathyroid hormone levels: a 16-year follow-up study.
AB  - High PTH levels increase bone turnover and decrease bone mineral density (BMD).
      Low plasma 25-hydroxyvitamin D (25OHD) levels cause secondary
      hyperparathyroidism, but the relative contribution of low 25OHD and high PTH
      levels on risk of fracture is largely unknown. Within the cohort of women (n =
      2,016) included in the Danish Osteoporosis Prevention Study (DOPS), we studied
      risk of fracture according to parathyroid status. Analyses were performed on
      effects of high PTH levels (i.e., in the upper tertile, >=4.5 pmol/L) on risk of
      incident fractures at different 25OHD levels during 16 years of follow-up.
      Incident fractures were assessed using a nationwide hospital discharge register.
      In addition, effects of high PTH levels on BMD and vertebral fractures were
      assessed by DXA scans and spinal X-ray examination after 10 years of follow-up.
      High PTH levels were associated with a decreased body mass index, adjusted BMD,
      and an increased risk of any fracture (HR = 1.41, 95% CI 1.11-1.79) as well as an
      increased risk of osteoporotic fractures (HR = 1.59, 95% CI 1.20-2.10). Plasma
      25OHD levels per se did not affect fracture risk, but high PTH levels were
      associated with an increased fracture risk only at 25OHD levels <50 nmol/L and 50
      80 nmol/L. High PTH levels did not increase risk of fracture at 25OHD levels >80
      nmol/L. In conclusion, PTH levels in the upper part or above the upper level of
      the reference interval increase risk of fracture in the presence of low vitamin D
      levels.

PMID- 21181399
TI  - [Advances in arthroscopic capsular labrum repair in ventral shoulder
      instability].
AB  - Current data show that the majority of patients in Germany with shoulder
      instability caused by soft tissue lesions are treated arthroscopically. The
      published redislocation rates in retrospective studies are less than 10%.
      Currently most surgeons prefer to use special strong suture materials and
      bioabsorbable suture anchors with a trend for knotless anchors. Some authors have
      published special techniques for labrum repair including double row fixation to
      increase the pull out force of the sutures but further prospective studies are
      necessary to prove whether these techniques can reduce the redislocation rate. In
      cases of extended anterior pouch of the capsule and in non-traumatic instability,
      capsular plication and interval closure can be indicated. There are still no
      clear objective parameters concerning indications or amount of plication and
      interval closure.

PMID- 21181401
TI  - Quantitative ultrasound measurements in premature infants at 1 year of age: the
      effects of antenatal administered corticosteroids.
AB  - The aim of this study was to evaluate the effects of antenatally administered
      glucocorticoids on bone status of preterm infants at 1 year corrected age. The
      study population consisted of 32 preterm infants with a gestational age of 24-34
      weeks. The infants were divided into two groups according to antenatal exposure
      to corticosteroids. Quantitative ultrasound (QUS) assessment of bone was
      performed in the study infants at the corrected age of 1 year. Blood levels of
      carboxy-terminal propeptide of type I procollagen (PICP) and carboxy-terminal
      telopeptide of type I collagen (ICTP) were measured at birth and at 1 year
      corrected age. Levels of PICP and ICTP were significantly lower at birth in
      corticosteroid-exposed neonates (P < 0.05). At corrected age of 12 months ICTP
      levels remained significantly lower in corticosteroid-exposed infants, but we
      found no significant difference in levels of the bone-formation marker PICP
      between corticosteroid-exposed and nonexposed infants. In the majority of
      participant preterm infants bone speed of sound (SOS) was within age-adjusted
      normal values of full-term infants. There was no significant difference in bone
      SOS between exposed and nonexposed infants at corrected age of 12 months. There
      was no correlation between SOS and levels of bone markers. The results of our
      study indicate that, despite the suppression of fetal bone turnover at birth in
      corticosteroid-exposed infants, antenatal glucocorticoid treatment seems to have
      no long-term impact on bone status of preterm infants assessed by QUS
      complementary to measurement of bone-turnover markers at 1 year corrected age.

PMID- 21181402
TI  - Deleterious mutations of a claw keratin in multiple taxa of reptiles.
AB  - We have recently shown that homologs of mammalian hair keratins are expressed in
      the claws of the green anole lizard, Anolis carolinensis. To test whether
      reptilian hair keratin homologs are functionally associated with claws, we
      investigated the conservation of the prototypical reptilian hair keratin homolog,
      hard acidic keratin 1 (HA1), in representative species from all main clades of
      reptiles. A complete cDNA of HA1 was cloned from the claw-forming epidermis of
      the lacertid lizard Podarcis sicula, and partial HA1 gene sequences could be
      amplified from genomic DNA of tuatara, lizards, gekkos, turtles, and crocodiles.
      In contrast, the HA1 gene of the limbless slow worm, Anguis fragilis, and of two
      species of turtles contained at least one deleterious mutation. Moreover, an HA1
      gene was undetectable in the softshell turtle, snakes, and birds. Mapping the
      presence and absence of HA1 onto the phylogenetic tree of sauropsids suggested
      that the HA1 gene has been lost independently in several lineages of reptiles.
      The species distribution of HA1 is compatible with the hypothesis of a primary
      function of HA1 in claws but also shows that the formation of reptilian claws
      does not strictly depend on this keratin.

PMID- 21181403
TI  - Analysis of acetabular version in the native hip: comparison between 2D axial CT
      and 3D CT measurements.
AB  - OBJECTIVE: To compare two-dimensional (2D) axial with three-dimensional (3D)
      computerized tomography (CT) measurements of acetabular version in native hips.
      MATERIALS AND METHODS: CT scans of 34 hips in 17 consecutive patients being
      investigated for femoroacetabular impingement were analyzed. Acetabular version
      was measured using 2D CT at two different axial levels, one cranial (slice 2) and
      the other at the equator (slice 3). The measurements were repeated after
      correction for pelvic tilt. The results were compared to the measurements of
      anatomical version obtained using a 3D CT method that automatically corrects for
      pelvic tilt. RESULTS: The mean acetabular version using the 3D CT method was 15.7
      degrees  (SD 6.9 degrees ). The mean version using slice 2 was 9.3 degrees  (SD
      6.5 degrees ) before correction for pelvic tilt and 15.7 degrees  (SD 8.0 degrees
      ) after the correction. The mean version using slice 3 was 16.4 degrees  (SD 4.2
      degrees ) before tilt correction and 19.0 degrees  (SD 5.0 degrees ) after the
      correction. In relation to the 3D method, the intraclass correlation coefficient
      (ICC) was 0.58 for the uncorrected and 0.93 for the corrected slice 2 method. For
      the uncorrected and corrected slice 3 methods, the ICC was 0.64 and 0.89,
      respectively. CONCLUSIONS: The 2D axial methods produced variable results. The
      results that correlated best with the 3D method were those of the cranial slice
      (slice 2) after correction for pelvic tilt. Interpretation of 2D axial CT
      measurements of acetabular version should be done with caution. The level at
      which the measurement is done and the presence of pelvic tilt appear to be
      significant factors.

PMID- 21181404
TI  - A novel tool for objective assessment of femorotibial rotation: a cadaver study.
AB  - Traumatic rupture of the anterior cruciate ligament (ACL) of the knee is one of
      the most frequent orthopaedic sports' injuries. However, the best operative
      reconstruction technique is still the focus of current discussions among experts.
      While single-bundle reconstruction primarily addresses anterior-posterior
      instability, the anatomical double-bundle reconstruction aims to stabilise
      anterior-posterior as well as rotational instability. So far no definite evidence
      to favour the one or the other technique exists due to the lack of an objective
      method for quantifying rotational knee stability. In this context several authors
      have recently reported on devices for the analysis of femorotibial rotation.
      However, most of these tools are still in the developmental stage. Therefore, the
      aim of this study was (1) to develop a new instrument for assessing rotational
      knee stability independent from the surrounding soft tissue with an adequate
      method of analysis and (2) to establish the possible field of application of this
      device in a human cadaver study. The so-called torsiometer evaluated was designed
      to assess internal and external knee joint rotation objectively in different
      flexion angles. Measurements were performed implying internal and external
      rotation at 90 degrees , 30 degrees  and 0 degrees  knee flexion with and without
      intact ACL, respectively. Each measurement revealed valid and reproducible
      values. The restraint in ACL-absent knees was clearly lower and the course of
      rotation explicitly higher than in knee joints with intact ACL.

PMID- 21181405
TI  - Antimicrobial activity and biodiversity of endophytic fungi in Dendrobium
      devonianum and Dendrobium thyrsiflorum from Vietnam.
AB  - Endophytic fungi are rich in orchids and have great impacts on their host plants.
      53 endophytes (30 isolates from Dendrobium devonianum and 23 endophytic fungi
      from D. thyrsiflorum) were isolated, respectively, from roots and stems of
      Dendrobium species. All the fungi were identified by way of morphological and/or
      molecular biological methods. 30 endophytic fungi in D. devonianum were
      categorized into 11 taxa and 23 fungal endophytes in D. thyrsiflorum were grouped
      into 11 genera, respectively. Fusarium was the dominant species of the two
      Dendrobium species in common. Antimicrobial activity of ethanol extract of
      fermentation broth of these fungi was explored using agar diffusion test. 10
      endophytic fungi in D. devonianum and 11 in D. thyrsiflorum exhibited
      antimicrobial activity against at least one pathogenic bacterium or fungus among
      6 pathogenic microbes (Escherichia coli, Bacillus subtilis, Staphylococcus
      aureus, Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus).
      Out of the fungal endophytes isolated from D. devonianum and D. thyrsiflorum,
      Phoma displayed strong inhibitory activity (inhibition zones in diameter >20 mm)
      against pathogens. Epicoccum nigrum from D. thyrsiflorum exhibited antibacterial
      activity even stronger than ampicillin sodium. Fusarium isolated from the two
      Dendrobium species was effective against the pathogenic bacterial as well as
      fungal pathogens. The study reinforced the assumption that endophytic fungi
      isolated from different Dendrobium species could be of potential antibacterial or
      antifungal resource.

PMID- 21181406
TI  - The Holy Grail in diagnostic neuroradiology: 3T or 3D?
AB  - Many technical developments keep occurring in the field of MRI that could benefit
      image acquisition in the field of diagnostic neuroradiology. While there is much
      focus on the potential advantages of 3T and higher field strengths, it is often
      unclear whether these are cosmetic only, or convey clinically relevant diagnostic
      value. The increased signal-to-noise at 3T is certainly beneficial in different
      ways particularly for the acquisition of isotropic 3D sequences like FLAIR.
      Single-slab 3D sequences can now be obtained with multiple contrasts in
      clinically attainable data acquisition times and could revolutionize MRI to
      evolve into a fundamentally multi-planar technique, rather similar to what has
      happened with the introduction of multi-detector row CT.

PMID- 21181407
TI  - Changes in AVM angio-architecture and hemodynamics after stereotactic
      radiosurgery assessed by dynamic MRA and phase contrast flow assessments: a
      prospective follow-up study.
AB  - OBJECTIVES: Assessment of changes in the hemodynamics of Arteriovenous
      malformations (AVM) induced by radiosurgery by MR Phase contrast (PC)
      measurements of the internal carotid arteries (ICA). METHODS: 65 patients shortly
      after or before stereotactic radiosurgery underwent MRI including morphological
      series, MR-Angiography (Time-of-flight, dynamic MRA) and bilateral ECG triggered
      MR phase contrast (PC) measurements of the ICA. Follow-up was performed in 34
      patients. The observation period was up to 4 years. RESULTS: Over all subjects, a
      significant relationship between mean arterial blood flow in the ICA on the side
      of the lesion and AVM volume was revealed (p = 0,0002). In large (>10 ccm) and
      medium-sized AVMs, (>3, 5 <= 10 ccm) the blood flow was significantly increased
      on the side of the AVM (p = 0,0004; p = 0,047), whereas in lesions <3, 5 ccm, no
      significant rise of the mean blood flow was detectable. At follow-up, the mean
      blood flow in the ipsilateral artery was not increased anymore compared to the
      contralateral ICA (p = 0,11). These changes correlated with a significant
      reduction of the average AVM volume (p = 0, 0026). CONCLUSIONS: The AVM
      angioarchitecture has significant impact on the blood flow in feeding arteries. A
      significant reduction of the shunt volume by successful radiotherapy leads to
      normalization of the hemodynamics.

PMID- 21181408
TI  - Musculoskeletal imaging: current and future trends.
AB  - Advances in imaging technology and the increasing role of interventional
      procedures in musculoskeletal imaging have continued to stimulate research over
      recent years. This review summarises some recent articles on musculoskeletal
      radiology topics and looks forward to potential future developments in this
      exciting sub-speciality.

PMID- 21181409
TI  - Laparoscopic colectomy is feasible in patients with left ventricular assist
      devices.

PMID- 21181410
TI  - The clinical efficacy of the vacuum-assisted closure therapy in the management of
      adult osteomyelitis.
AB  - INTRODUCTION: Vacuum-assisted closure (VAC) therapy is a sophisticated
      development of a standard surgical procedure. The purpose of this study is to
      evaluate the clinical efficacy of managing adult osteomyelitis with VAC therapy.
      MATERIALS AND METHODS: We included a total of 68 patients that developed
      osteomyelitis with Cierny-Mader types 2, 3 and 4, and required open wound
      management between March 2005 and February 2009. In this study, 35 of these
      patients were treated by VAC therapy and the other 33 by conventional wound
      management. The patients were well compared with type, debridement times, wounds
      coverage, bacteriology and recurrence. RESULTS: Of the study, the patients
      treated by VAC therapy had a significantly reduced recurrence (1 vs. 7 wounds, P
      < 0.05), decreased rate of further autodermoplasty or flap surgery (17 vs. 26
      wounds, P < 0.05), and increased cases of bacterial species cultures to negative
      (29 vs. 15 wounds, P < 0.05), debridement times and type were similar between the
      two groups. CONCLUSION: VAC therapy represents a good clinical efficacy in
      treating osteomyelitis; it can promote the granulation tissue formation,
      bacterial clearance, and reduce the needs for tissue transfer and muscle flaps in
      patients. In addition, it could be used as an adjuvant for the eradication of
      osteomyelitis and improving soft-tissue management, it may be more suitable for
      treating osteomyelitis with soft-tissue problems.

PMID- 21181411
TI  - Welcome to the Ipad generation.

PMID- 21181412
TI  - Time-specific blockade of PDGFR with Imatinib (Glivec(r)) causes cataract and
      disruption of lens fiber cells in neonatal mice.
AB  - This study aimed at investigating the response of lens epithelial cells in
      postnatal mice to Imatinib (Glivec(r), a potent inhibitor of platelet-derived
      growth factor receptor (PDGFR)) treatment. Mouse eyes were sampled 10 days after
      administration of Imatinib (0.5 mg.g(-1).day(-1)) for 3 days, at either 7, 14, or
      21 days postpartum. Structural changes of lens were revealed by routine H.E.
      staining. Levels of proliferation and apoptosis were revealed by BrdU
      incorporation and terminal deoxynucleotidyl transferase dUTP nick end labeling
      (TUNEL) assay, respectively, and immunofluorescent staining with anti-PDGFRalpha
      antibody was carried out on the sections of eyeball. PDGFRalpha and p
      PDGFRalphaprotein levels were evaluated by Western blot. Our results indicated
      that administration of Imatinib led to blockade of PDGFR signaling. Formation of
      cataracts was found only in those mice where treatment started from 7 days
      postpartum (P7), but was not observed in those samples from P14 nor P21. Fiber
      cells were disorganized in cataract lens core as observed histologically, and
      migration of epithelial cells was also inhibited. No apoptosis was detected with
      the TUNEL method. Our results indicated blockade of PDGFR at the neonatal stage
      (P7) would lead to cataracts and lens fiber cells disorganization, suggesting
      that PDGFR signaling plays a time-specific and crucial role in the postnatal
      development of lens in the mouse, and also may provide a new approach to produce
      a congenital cataract animal model.

PMID- 21181413
TI  - The many faces of atypical Ewing's sarcoma. A true entity mimicking sarcomas,
      carcinomas and lymphomas.
AB  - Ewing's sarcoma family of tumours (ESFT) comprises a group of small round cell
      tumours (SRCT) genetically defined by specific chromosomal translocations
      resulting in a fusion of the EWSR1 gene with a member of the ETS family of
      transcription factors. Atypical ESFT are the most challenging of the ESFT
      subtypes, and the differential diagnosis with other SRCT of bone and soft tissue
      is difficult since these subtypes can resemble other neoplasms. The present
      article describes nine cases of genetically confirmed, atypical ESFT, having
      unusual alterations at morphological and immunohistochemical (IHC) levels
      associated with atypical clinical presentation mimicking sarcomas, carcinomas and
      lymphomas. Present results demonstrate that ESFT showing overlapping
      morphological and immunohistochemical features with other SRCT of soft tissue and
      bone, or even with carcinomas or lymphoma, can be differentiated using molecular
      techniques. In SRCT with EWSR1 translocation demonstrated by FISH, the RT-PCR
      analysis of specific sarcoma-related gene fusion can offer important clues for
      the diagnosis of specific entities, especially in tumours with unusual
      histopathology and/or IHC findings. Thus, we confirm that the integration of
      clinical, histopathological, IHC and genetic data becomes decisive in the
      diagnosis of bone and soft tissue sarcomas.

PMID- 21181414
TI  - PTOV1 is overexpressed in human high-grade malignant tumors.
AB  - The prostate tumor overexpressed-1 (PTOV1) protein was first described
      overexpressed in prostate cancer but not detected in normal prostate. PTOV1
      expression is associated to increased cancer proliferation in vivo and in vitro.
      In prostate biopsy, PTOV1 detection is helpful in the early diagnosis of cancer.
      The purpose of this study was to analyze the relevance of PTOV1 expression to
      identify aggressive tumors derived from 12 different histological tissues. Tissue
      microarrays (TMAs) containing 182 biopsy samples, including 168 human tumors,
      were analyzed for PTOV1 and Ki67 expression by immunohistochemistry. Tumors of
      low and high histological grade were selected from lung, breast, endometrium,
      pancreas liver, skin, ovary, colon, stomach, kidney, bladder, and cerebral
      gliomas. One TMA with representative tissues without cancer (14 samples) was used
      as control. PTOV1 expression was analyzed semiquantitatively for the intensity
      and percentage of positive cells. Ki67 was evaluated for tumors proliferative
      index. Results show that PTOV1 was expressed in over 95% of tumors examined. Its
      expression was significantly associated to high-grade tumors (p = 0.014). This
      association was most significant in urothelial bladder carcinomas (p = 0.026).
      Overall, the expression of Ki67 was associated to high-grade tumors, and it was
      significant in several tumor types. PTOV1 and Ki67 were significantly co
      overexpressed in all tumors (p = 0.001), and this association was significant in
      clear cell renal carcinoma (p = 0.005). In conclusion, PTOV1 expression is
      associated to more aggressive human carcinomas and more significantly to bladder
      carcinomas suggesting that this protein is a potential new marker of aggressive
      disease in the latter tumors.

PMID- 21181415
TI  - Toward a mechanistic understanding of competition in vascular-feeding herbivores:
      an empirical test of the sink competition hypothesis.
AB  - Recent evidence suggests that competitive interactions among herbivores are
      mostly indirect and mediated by plant responses to herbivory. Most studies,
      however, emphasize chewing insects and secondary chemistry, thus ignoring the
      diverse group of vascular-parasites that may be more likely to compete through
      induced changes in phytonutrients. Using an aboveground phloem-feeding aphid
      (Myzus persicae) and a belowground gall-forming nematode (Meloidogyne incognita)
      on tobacco plants, we assessed the importance of competition via induced host
      plant sinks. In a series of experimental trials, nematode root herbivory caused
      55 and 72% declines in the growth and fecundity of aphids, respectively. Aphids,
      on the other hand, did not impact nematode performance. Therefore, we predicted
      that nematodes out-compete M. persicae by attenuating the magnitude of aphid
      induced sinks. Through a combination of invertase enzyme measurements and stable
      isotope ((13)C and (15)N) enrichment, we found evidence that both herbivores act
      as mobilizing sinks. Aphids attracted photoassimilates to feeding aggregations on
      leaves and nematode galls accumulated resources in the roots. Levels of invertase
      enzymes, for example, were more than fourfold higher in nematode galls than in
      surrounding root tissue. Yet we found no evidence supporting a sink competition
      model for aphid-nematode interactions. The strength of aphid-induced leaf sinks
      was entirely unaffected by nematode presence, and vice versa. Thus, induced host
      plant sinks appear to be a common strategy employed by vascular parasites to
      manipulate the physiology of their host, but multi-sink competition may be
      limited to herbivores that co-occur on the same tissue type and/or plants under
      growth-limited abiotic conditions.

PMID- 21181416
TI  - Vulnerability of black grouse hens to goshawk predation: result of food supply or
      predation facilitation?
AB  - The plant cycle hypothesis says that poor-quality food affects both herbivorous
      voles (Microtinae spp.) and grouse (Tetraonidae spp.) in vole decline years,
      leading to increased foraging effort in female grouse and thus a higher risk of
      predation by the goshawk Accipiter gentilis. Poor-quality food (mainly the
      bilberry Vaccinium myrtillus) for these herbivores is induced by seed masting
      failure in the previous year, when the bilberry is able to allocate resources for
      chemical defence (the mast depression hypothesis; MDH). The predation
      facilitation hypothesis (PFH) in turn states that increased searching activity of
      vole-eating predators during or after the decline year of voles disturbs
      incubating and brooding grouse females. The behaviours used by grouse to avoid
      these terrestrial predators make them more vulnerable to predation by goshawks.
      We tested the main predictions of the MDH and PFH by collecting long-term (21
      year) data from black grouse Tetrao tetrix hens and cocks killed by breeding
      goshawks supplemented with indices of bilberry crop, vole abundance and small
      carnivores in the vicinity of Oulu, northern Finland. We did not find obvious
      support for the prediction of the MDH that there is a negative correlation of
      bilberry crop in year t with vole abundance and with predation index of black
      grouse hens in year t + 1. We did find obvious support for the prediction of the
      PFH that there is a positive correlation between predator abundance and predation
      index of grouse hens, because the stoat Mustela erminea abundance index was
      positively related to the predation index of black grouse hens. We suggest that
      changes in vulnerability of grouse hens may mainly be caused by the guild of vole
      eating predators, who shift to alternative prey in the decline phase of the vole
      cycle, and thus chase grouse hens and chicks to the talons of goshawks and other
      avian predators.

PMID- 21181418
TI  - [Glossopharyngeal neuralgia after resection of a glossopharyngeal schwannoma].
AB  - Glossopharyngeal neuralgia is a rare condition and the origin is mostly
      idiopathic. Causes of symptomatic glossopharyngeal neuralgia can be tumors,
      infarction or trauma. We report the case of a 28-year-old patient who developed
      glossopharyngeal neuralgia after resection of a glossopharyngeal schwannoma,
      which is an extremely rare tumor. Treatment consisted of orally administered
      pregabalin and a series of injections of buprenorphine in the superior cervical
      ganglion (ganglionic local opioid application/analgesia, GLOA) which led to a
      substantial decrease in the frequency of pain attacks. This improvement was
      maintained at 1-year follow-up. This is the first report of development of
      glossopharyngeal neuralgia after resection of a glossopharyngeal schwannoma.

PMID- 21181417
TI  - [Pregabalin and postoperative hyperalgesia. A review].
AB  - Numerous studies support the theory that pregabalin causes an antihyperalgesic
      effect, which could be potentially beneficial in a perioperative setting. By
      binding to calcium channels pregabalin reduces the release of excitatory
      neurotransmitters and therefore inhibits central sensitization. Animal studies
      clearly demonstrated the antihyperalgesic potency of pregabalin but human
      experiments are, however, inconclusive. Clinical studies with quantitative
      sensory testing have not yet been published. Although strongly supported by
      theoretical considerations the routine preoperative application of pregabalin for
      the prevention of hyperalgesia cannot be recommended due to the lack of clinical
      studies. Future studies should incorporate secondary hyperalgesia and allodynia
      as primary parameters.

PMID- 21181419
TI  - A case of intraoperative coronary artery spasm in a patient with vascular
      disease.
AB  - A 66-year-old man with a history of longtime smoking, untreated hypertension,
      hyperlipidemia, and impaired glucose tolerance but no history of myocardial
      infarction or angina pectoris was scheduled for right aortofemoral bypass and
      thromboembolectomy for arteriosclerosis obliterans with right common iliac and
      right popliteal arterial thrombus. Epidural anesthesia and general anesthesia
      were administered without obvious ECG changes. Just after skin incision, ST
      elevation in leads II and V5 and a short run of ventricular tachycardia with
      frequent premature ventricular contractions (PVCs) were recorded on the ECG
      monitor, and the patient's blood pressure suddenly decreased within a few
      seconds. On noticing these changes, we suspected coronary artery spasm (CAS) and
      rapidly administered vasodilators and vasopressors to stabilize hemodynamics and
      ECG changes. Transesophageal echocardiography (TEE) showed basal to mid- and
      anteroseptal to inferior wall motion hypokinesis that gradually returned to
      normal during observation. Even in patients without coronary disease but with
      systemic arteriosclerosis, it is important to consider the possibility of
      perioperative CAS and not to overlook ECG changes. Immediate diagnosis and
      treatment are essential.

PMID- 21181420
TI  - Nitrative and oxidative modifications of enolase are associated with iron in iron
      overload rats and in vitro.
AB  - Iron overload is one of the most common iron-related toxicities, and liver is the
      major organ that is injured. Although oxidative stress is well accepted in the
      pathological mechanism of iron overload, nitrative modification in liver and the
      role of iron are relatively unknown. In this work, the nitrative and oxidative
      stress in liver was investigated in an iron-overload rat model. It was found that
      after 15 weeks of iron dextran administration, consistent with the increase of
      iron content in rat liver, both protein tyrosine nitration and protein oxidation
      were clearly elevated. By means of immunoprecipitation analysis, it was found
      that enolase nitration and oxidation status were significantly increased in iron
      overload liver, whereas both alpha-enolase expression and activity were clearly
      decreased. The effects of different forms of iron on NaNO(2)-H(2)O(2)- and
      peroxynitrite (ONOO(-))-dependent enolase nitration and oxidation were further
      investigated in vitro to elucidate the possible role of iron in enolase
      dysfunction in vivo. Compared with EDTA-Fe(III), ferric citrate, and ferritin,
      heme (hemin and hemoglobin) showed higher efficiency in catalyzing protein
      nitration in both models. Besides the major contribution of free iron (Fe(2+) and
      Fe(3+)) to catalyze protein oxidation, Fe(2+) also directly acted as a
      competitive inhibitor and produced a significant decrease in enzyme activity.
      These results suggest that the existence of various forms of iron is an important
      contributing factor to the elevated nitrative/oxidative modifications and
      diminished activity of alpha-enolase in the development and progress of iron
      overload-associated syndromes.

PMID- 21181421
TI  - Sco proteins are involved in electron transfer processes.
AB  - Sco proteins are widespread in eukaryotic and in many prokaryotic organisms. They
      have a thioredoxin-like fold and bind a single copper(I) or copper(II) ion
      through a CXXXC motif and a conserved His ligand, with both tight and weak
      affinities. They have been implicated in the assembly of the Cu(A) site of
      cytochrome c oxidase as copper chaperones and/or thioredoxins. In this work we
      have structurally characterized a Sco domain which is naturally fused with a
      typical electron transfer molecule, i.e., cytochrome c, in Pseudomonas putida.
      The thioredoxin-like Sco domain does not bind copper(II), binds copper(I) with
      weak affinity without involving the conserved His, and has redox properties
      consisting of a thioredoxin activity and of the ability of reducing copper(II) to
      copper(I), and iron(III) to iron(II) of the cytochrome c domain. These findings
      indicate that the His ligand coordination is the discriminating factor for
      introducing a metallochaperone function in a thioredoxin-like fold, typically
      responsible for electron transfer processes. A comparative structural analysis of
      the Sco domain from P. putida versus eukaryotic Sco proteins revealed structural
      determinants affecting the formation of a tight-affinity versus a weak-affinity
      copper binding site in Sco proteins.

PMID- 21181422
TI  - Molecular cloning, modeling, and site-directed mutagenesis of type III polyketide
      synthase from Sargassum binderi (Phaeophyta).
AB  - Type III polyketide synthases (PKSs) produce an array of metabolites with diverse
      functions. In this study, we have cloned the complete reading frame encoding type
      III PKS (SbPKS) from a brown seaweed, Sargassum binderi, and characterized the
      activity of its recombinant protein biochemically. The deduced amino acid
      sequence of SbPKS is 414 residues in length, sharing a higher sequence similarity
      with bacterial PKSs (38% identity) than with plant PKSs. The Cys-His-Asn
      catalytic triad of PKS is conserved in SbPKS with differences in some of the
      residues lining the active and CoA binding sites. The wild-type SbPKS displayed
      broad starter substrate specificity to aliphatic long-chain acyl-CoAs (C(6)
      C(14)) to produce tri- and tetraketide pyrones. Mutations at H(331) and N(364)
      caused complete loss of its activity, thus suggesting that these two residues are
      the catalytic residues for SbPKS as in other type III PKSs. Furthermore, H227G,
      H227G/L366V substitutions resulted in increased tetraketide-forming activity,
      while wild-type SbPKS produces triketide alpha-pyrone as a major product. On the
      other hand, mutant H227G/L366V/F93A/V95A demonstrated a dramatic decrease of
      tetraketide pyrone formation. These observations suggest that His(227) and
      Leu(366) play an important role for the polyketide elongation reaction in SbPKS.
      The conformational changes in protein structure especially the cavity of the
      active site may have more significant effect to the activity of SbPKS compared
      with changes in individual residues.

PMID- 21181423
TI  - Occurrence of a silicatein gene in glass sponges (Hexactinellida: Porifera).
AB  - Silicatein genes are involved in spicule formation in demosponges (Demospongiae:
      Porifera). However, numerous attempts to isolate silicatein genes from glass
      sponges (Hexactinellida: Porifera) resulted in a limited success. In the present
      investigation, we performed analysis of potential silicatein/cathepsin
      transcripts in three different species of glass sponges (Pheronema raphanus,
      Aulosaccus schulzei, and Bathydorus levis). In total, 472 clones of such
      transcripts have been analyzed. Most of them represent cathepsin transcripts and
      only three clones have been found to represent transcripts, which can be related
      to silicateins. Silicatein transcripts were identified in A. schulzei
      (Hexactinellida; Lyssacinosida; Rosselidae), and the corresponding gene was
      called AuSil-Hexa. Expression of AuSil-Hexa in A. schulzei was confirmed by real
      time PCR. Comparative sequence analysis indicates high sequence identity of the
      A. schulzei silicatein with demosponge silicateins described previously. A
      phylogenetic analysis indicates that the AuSil-Hexa protein belongs to
      silicateins. However, the AuSil-Hexa protein contains a catalytic cysteine
      instead of the conventional serine.

PMID- 21181424
TI  - Terpenes from the red alga Sphaerococcus coronopifolius inhibit the settlement of
      barnacles.
AB  - In this study, we screened eight terpenes isolated from the organic extract of
      Sphaerococcus coronopifolius for their antifouling activity in order to find
      possible new sources of non-toxic or less toxic bioactive antifoulants. The anti
      settlement activity (EC50) and the degree of toxicity (LC50) of S. coronopifolius
      metabolites was evaluated using larvae of the cirriped crustacean Amphibalanus
      (Balanus) amphitrite (cyprids and nauplii) as model organism. For five of eight
      tested metabolites EC50 was lower than 5 mg/L. The most promising results were
      observed for bromosphaerol (3), which expressed an EC50 value of 0.23 mg/L, in
      combination with low toxicity levels (LC50 > 100 mg/L). The therapeutic ratio--an
      index used to estimate whether settlement inhibition is due to toxicity or other
      mechanisms--is also calculated and discussed.

PMID- 21181425
TI  - Self-medication of migraine and tension-type headache: summary of the evidence
      based recommendations of the Deutsche Migrane und Kopfschmerzgesellschaft (DMKG),
      the Deutsche Gesellschaft fur Neurologie (DGN), the Osterreichische
      Kopfschmerzgesellschaft (OKSG) and the Schweizerische Kopfwehgesellschaft (SKG).
AB  - The current evidence-based guideline on self-medication in migraine and tension
      type headache of the German, Austrian and Swiss headache societies and the German
      Society of Neurology is addressed to physicians engaged in primary care as well
      as pharmacists and patients. The guideline is especially concerned with the
      description of the methodology used, the selection process of the literature used
      and which evidence the recommendations are based upon. The following
      recommendations about self-medication in migraine attacks can be made: The
      efficacy of the fixed-dose combination of acetaminophen, acetylsalicylic acid and
      caffeine and the monotherapies with ibuprofen or naratriptan or acetaminophen or
      phenazone are scientifically proven and recommended as first-line therapy. None
      of the substances used in self-medication in migraine prophylaxis can be seen as
      effective. Concerning the self-medication in tension-type headache, the following
      therapies can be recommended as first-line therapy: the fixed-dose combination of
      acetaminophen, acetylsalicylic acid and caffeine as well as the fixed combination
      of acetaminophen and caffeine as well as the monotherapies with ibuprofen or
      acetylsalicylic acid or diclofenac. The four scientific societies hope that this
      guideline will help to improve the treatment of headaches which largely is
      initiated by the patients themselves without any consultation with their
      physicians.

PMID- 21181426
TI  - Reduced bowel sounds in Parkinson's disease and multiple system atrophy patients.
AB  - Digital auscultation of bowel sounds was performed in newly diagnosed, drug-naive
      patients with Parkinson's disease (PD) (n = 10), multiple system atrophy (MSA) (n
      = 12), progressive supranuclear palsy/corticobasal degeneration (PSP/CBD) (n =
      7), and control subjects (n = 18). The number of bowel sounds per minute and the
      integrated time of bowel sounds were significantly lower in PD and MSA patients
      than in control subjects. Reduced bowel sounds may herald compromised
      gastrointestinal motility in patients with PD and MSA.

PMID- 21181427
TI  - Post-translational processing of modular xylanases from Streptomyces is dependent
      on the carbohydrate-binding module.
AB  - Xylanases are very often modular enzymes composed of one or more catalytic
      domains and carbohydrate-binding modules (CBMs) connected by a flexible linker
      region. Usually, when these proteins are processed they lose their carbohydrate
      binding capacity. Here, the role of the linker regions and cellulose- or xylan
      binding domains in the processing of Xys1L from Streptomyces halstedii JM8 and
      Xyl30L from Streptomyces avermitilis UAH30 was studied. Xys1 variants with
      different linker lengths were tested, these being unable to avoid protein
      processing. Moreover, several fusion proteins between the Xys1 and Xyl30 domains
      were obtained and their proteolytic stability was studied. We demonstrate that
      CBM processing takes place even in the complete absence of the linker sequence.
      We also show that the specific carbohydrate module determines this cleavage in
      the proteins studied.

PMID- 21181428
TI  - Calcium alginate entrapped preparation of alpha-galactosidase: its stability and
      application in hydrolysis of soymilk galactooligosaccharides.
AB  - Thermostable alpha-galactosidase from Aspergillus terreus (GR) was insolubilized
      using concanavalin A obtained from jack bean extract and in order to maintain the
      integrity of complex in the presence of its substrate or products, this complex
      was crosslinked with glutaraldehyde. Soluble alpha-galactosidase entrapped in
      calcium alginate retained 82% of enzyme activity whereas, Con A-alpha
      galactosidase complex entrapped in calcium alginate and crosslinked Con A-alpha
      galactosidase complex entrapped calcium alginate retained 74 and 61% activity,
      respectively. A fluidized bed reactor was constructed for continuous hydrolysis
      of galactooligosaccharides in soymilk using crosslinked Con A-alpha-galactosidase
      complex entrapped calcium alginate. Optimum conditions such as pH (5.0) and
      temperature (65 degrees C) were the same for all immobilized enzyme preparations
      and soluble enzyme. Crosslinked Con A-alpha-galactosidase entrapped complex
      exhibited enhanced thermostability and showed 62% of activity (38%) after 360 min
      at 65 degrees C. Entrapped crosslinked Con A-alpha-galactosidase complex
      preparation was superior in the continuous hydrolysis of oligosaccharides in
      soymilk by batch processes compared to the other entrapped preparations. The
      entrapped crosslinked concanavalin A-alpha-galactosidase complex retained 95%
      activity after eight cycles of use.

PMID- 21181429
TI  - DFT calculation of four new potential agents muscarinic of bispyridinium type:
      structure, synthesis, biological activity, hydration, and relations with the
      potents W84 and DUO-3O.
AB  - Four new potential agents muscarinic (allosteric modulators) were synthesized and
      studied by using the B3LYP density functional method. The optimum conformation
      and geometry structure of these compounds were determined and analyzed. Solvent
      effects were considered including a variable number (1-15) of explicit water
      molecules surrounding the compound in order to simulate the first hydration
      shell, as well as using the Tomasi's polarized continuum model (PCM). A similar
      simultaneous analysis of the potents W84 and DUO-3O allosteric modulator of
      muscarinic receptors was also carried out. The effect of the hydration on the
      total atomic charges and several intermolecular distances of interest were also
      discussed. The biological activity against acetylcholine of our four synthesized
      bispyridinium salts was determined. Relationships/tendencies structure-activity
      were established. Several general conclusions were underlined.

PMID- 21181430
TI  - Between biochemists and embryologists -- the biochemical study of embryonic
      induction in the 1930s.
AB  - The discovery by Hans Spemann of the "organizer" tissue and its ability to induce
      the formation of the amphibian embryo's neural tube inspired leading
      embryologists to attempt to elucidate embryonic inductions' underlying mechanism.
      Joseph Needham, who during the 1930s conducted research in biochemical
      embryology, proposed that embryonic induction is mediated by a specific chemical
      entity embedded in the inducing tissue, surmising that chemical to be a hormone
      of sterol-like structure. Along with embryologist Conrad H. Waddington, they
      conducted research aimed at the isolation and functional characterization of the
      underlying agent. As historians clearly pointed out, embryologists came to
      question Needham's biochemical approach; he failed to locate the hormone he
      sought and eventually abandoned his quest. Yet, this study finds that the
      difficulties he ran into resulted primarily from the limited conditions for
      conducting his experiments at his institute. In addition, Needham's research
      reflected the interests of leading biochemists in hormone and cancer research,
      because it offered novel theoretical models and experimental methods for engaging
      with the function of the hormones and carcinogens they isolated. Needham and
      Waddington were deterred neither by the mounting challenges nor by the limited
      experimental infrastructure. Like their colleagues in hormone and cancer
      research, they anticipated difficulties in attempting to establish causal links
      between complex biological phenomena and simple chemical triggering.

PMID- 21181431
TI  - Stromal mediation of radiation carcinogenesis.
AB  - Ionizing radiation is a well-established carcinogen in human breast and rodent
      mammary gland. This review addresses evidence that radiation elicits the critical
      stromal context for cancer, affecting not only frequency but the type of cancer.
      Recent data from the breast tumors of women treated with radiation therapy and
      the cellular mechanisms evident in experimental models suggest that radiation
      effects on stromal-epithelial interactions and tissue composition are a major
      determinant of cancer development.

PMID- 21181432
TI  - IL-1 receptor accessory protein-Ig/IL-1 receptor type II-Ig heterodimer inhibits
      IL-1 response more strongly than other IL-1 blocking biopharmaceutical agents.
AB  - INTRODUCTION: Interleukin (IL)-1 is a key orchestrator of inflammation and IL-1
      inhibitors are expected to be promising pharmaceutical agents for such
      pathologies. IL-1 is bound to the complex of two receptor components with much
      higher affinity than with either receptor component alone. MATERIALS AND METHODS:
      We examined the effect of a heterodimer of IL-1 receptor accessory protein (Acp)
      immunoglobulin (Ig) and IL-1R type II (IL1R2)-Ig named AcP-Ig/IL1R2-Ig
      heterodimer, and compared its effects with other IL-1 inhibitors reported
      previously. RESULTS AND DISCUSSION: Our results demonstrated that the rat AcP
      Ig/IL1R2-Ig heterodimer (IC50=1.95 pM) inhibited IL-1 response to a greater
      extent than IL1RA (IC50=1,935 pM), Acp-IL1R type I (IL1R1)-Ig homodimer
      (IC50=73.7 pM) and Acp-IL1R2-Ig homodimer (IC50=72.8 pM). Moreover, human AcP
      Ig/IL1R2-Ig heterodimer (IC50=0.14 pM) inhibited it to a greater extent than Acp
      IL1R1-Ig homodimer (IC50=4.48 pM) and strongly inhibited responses of both IL
      1alpha and IL-1beta. CONCLUSIONS: The AcP-Ig/IL1R2-Ig heterodimer, which is
      similar to the original extracellular structure of the Acp/IL1R1 complex, may
      inhibit the IL-1 response more vigorously than other IL-1 blocking
      biopharmaceutical agents.

PMID- 21181433
TI  - Association of metabolic syndrome with reduced central serotonergic activity.
AB  - The aim of this study was to determine the differences between two groups of
      adolescents with metabolic syndrome (MetS) and normal controls in relation to
      brain serotonergic activity through intensity-dependent auditory-evoked
      potentials (IDAEPs) and plasma free fraction of L-tryptophan. Eighteen
      adolescents with MetS and thirteen controls were studied. Free fraction, bound
      and total plasma L-tryptophan, glucose, cholesterol, triglycerides, HDL
      cholesterol, albumin and IDAEPs were determined. Glycemia, triglycerides were
      significantly elevated, and HDL-cholesterol in plasma was significantly reduced.
      Free fraction and free fraction/total L-tryptophan ratio were decreased. The
      slope of the amplitude/stimulus intensity function of the N1/P2 component
      significantly increased in adolescents with MetS. Decrease of free fraction of L
      tryptophan in plasma and increase of the slope of the N1/P2 component suggest a
      low brain serotonin tone. Cortex responses are regulated by serotonergic
      innervations and may show a different behavior in young patients with MetS.
      Therefore, the slope of the N1/P2 component along with the free fraction of L
      tryptophan in plasma, indicate that in adolescents with MetS the state of
      serotonergic brain activity is depressed and possibly related to psychiatric
      disorders.

PMID- 21181434
TI  - Personality correlates of the common and unique variance across conduct disorder
      and substance misuse symptoms in adolescence.
AB  - Externalising behaviours such as substance misuse (SM) and conduct disorder (CD)
      symptoms highly co-occur in adolescence. While disinhibited personality traits
      have been consistently linked to externalising behaviours there is evidence that
      these traits may relate differentially to SM and CD. The current study aimed to
      assess whether this was the case, after examining the nature of the relationship
      between SM and CD symptoms in an adolescent sample (N = 392), using structural
      equation modelling. Similar to those found in adults (Krueger et al. Journal of
      Abnormal Psychology 116: 645-666, 2007), results showed that CD and SM symptoms
      were organized hierarchically, with symptoms explaining a single broad, coherent
      construct of externalising behaviour, but also explaining specific factors of SM
      and CD that vary independently from the general externalising factor.
      Furthermore, disinhibited personality traits related differentially to these
      factors, with results showing that, even controlling for inhibited personality
      traits, impulsivity was associated with CD and the common variance shared by CD
      and SM, while sensation seeking was specifically associated with SM only.
      Hopelessness was also associated with the common variance shared by SM and CD.
      Results confirm impulsivity, hopelessness and sensation seeking as key correlates
      of externalising behaviour problems in adolescence, identifying them as clear
      targets for intervention and prevention strategies.

PMID- 21181435
TI  - The role of pre- and postnatal timing of family risk factors on child behavior at
      36 months.
AB  - Children growing up in disharmonious families with anxious/depressed mothers are
      at risk for emotional and behavioral difficulties, however whether these
      associations reflect postnatal environment, prenatal exposure, or an overall
      liability is still unclear. This study used prospectively collected data from
      24,259 participants of the Norwegian Mother and Child Cohort Study (MoBa).
      Mothers reported on anxiety/depression and family disharmony twice in pregnancy
      and twice post pregnancy, as well as on their child's physical aggression and
      crying behavior at age 36 months. First, results from an autoregressive cross
      lagged model showed a substantial stability in both maternal anxiety/depression
      and family disharmony from pregnancy to 18 months postnatal, but there was no
      indication that family disharmony led to maternal anxiety/depression, or the
      other way around. Second, structural equation models further suggests that the
      main risk derived from an overall liability, that is, a lasting effect of family
      risks that spanned the two time periods.

PMID- 21181436
TI  - Post-lumpectomy intracavitary retention and lymph node targeting of (99m)Tc
      encapsulated liposomes in nude rats with breast cancer xenograft.
AB  - Liposomes are recognized drug delivery systems with tumor-targeting capability.
      In addition, therapeutic or diagnostic radionuclides can be efficiently loaded
      into liposomes. This study investigated the feasibility of utilizing
      radiotherapeutic liposomes as a new post-lumpectomy radiotherapy for early-stage
      breast cancer by determining the locoregional retention and systemic distribution
      of liposomes radiolabeled with technetium-99m ((99m)Tc) in an orthotopic MDA-MB
      231 breast cancer xenograft nude rat model. To test this new brachytherapy
      approach, a positive surgical margin lumpectomy model was set up by surgically
      removing the xenograft and deliberately leaving a small tumor remnant in the
      surgical cavity. Neutral, anionic, and cationic surface-charged fluorescent
      liposomes of 100 and 400 nm diameter were manufactured and labeled with (99m)Tc
      BMEDA. Locoregional retention and systemic distribution of (99m)Tc-liposomes
      injected into the post-lumpectomy cavity were determined using non-invasive
      nuclear imaging, ex vivo tissue gamma counting and fluorescent stereomicroscopic
      imaging. The results indicated that (99)Tc-liposomes were effectively retained in
      the surgical cavity (average retention was 55.7 +/- 24.2% of injected dose for
      all rats at 44 h post-injection) and also accumulated in the tumor remnant (66.9
      +/- 100.4%/g for all rats). The majority of cleared (99m)Tc was metabolized
      quickly and excreted into feces and urine, exerting low radiation burden on vital
      organs. In certain animals (99m)Tc-liposomes significantly accumulated in the
      peripheral lymph nodes, especially 100 nm liposomes with anionic surface charge.
      The results suggest that post-lumpectomy intracavitary administration of
      therapeutic radionuclides delivered by 100-nm anionic liposome carrier is a
      potential therapy for the simultaneous treatment of the surgical cavity and the
      draining lymph nodes of early-stage breast cancer.

PMID- 21181437
TI  - PH006, a novel and selective Src kinase inhibitor, suppresses human breast cancer
      growth and metastasis in vitro and in vivo.
AB  - The central role of Src in tumor progression and metastasis has validated it as
      an attractive therapeutic target for the treatment of human breast cancer. The
      aim of this study was to identify potential Src kinase inhibitor, explore its
      activity, and mechanism of action in human breast cancer. A strategy integrating
      focused combinatorial library design, virtual screening, chemical synthesis, and
      high-throughput screening was adopted and a novel 6-hydrazinopurine-based
      inhibitor of c-Src kinase PH006 was obtained. The kinase enzymatic activities
      were measured by enzyme-linked immunosorbent assay. The binding mode between
      PH006 and Src was profiled by surface plasmon resonance approach and molecular
      simulation. The anti-proliferative activity was evaluated by Sulforhodamin B
      (SRB) and Colony formation. The anti-invasion and anti-migration activities were
      assessed by trans-well and wound healing assay. Results indicated that PH006 was
      an ATP-competitive Src inhibitor, which selectively inhibited c-Src with an IC50
      of 0.38 MUM among a panel of 14 diverse tyrosine kinases. PH006 potently
      inhibited c-Src phosphorylation and c-Src-dependent signal transduction,
      resulting in inhibition of cell proliferation, migration, and invasion in human
      breast cancer MDA-MB-231 cells. Further study demonstrated that the anti
      proliferative activity of PH006 was ascribed to its capability to arrest cells in
      G1 phase, while its anti-motility activity was related to suppression of MMP2/9
      and HGF secretion. Moreover, PH006 exhibited potent activity against tumor growth
      as well as metastasis of human breast cancer MDA-MB-435 xenograft beard in nude
      mice, which was accompanied with reduced Src/FAK signaling in tumor tissue. Taken
      together, PH006 is a novel selective inhibitor of c-Src and possesses potent
      activity against breast cancer growth and metastasis, which could be potentially
      developed as a lead candidate against breast cancers with elevated Src tyrosine
      kinase activity.

PMID- 21181439
TI  - High efficiency of BRCA1 knockout using rAAV-mediated gene targeting: developing
      a pig model for breast cancer.
AB  - Germline inactivating mutations of the breast cancer associated gene 1 (BRCA1)
      predispose to breast cancer and account for most cases of familiar breast and/or
      ovarian cancer. The pig is an excellent model for medical research as well as
      testing of new methods and drugs for disease prevention and treatment. We have
      generated cloned BRCA1 knockout (KO) Yucatan miniature piglets by targeting exon
      11 using recombinant adeno-associated virus (rAAV)-mediated gene targeting and
      somatic cell nuclear transfer by Handmade Cloning (HMC). We found a very high
      targeting rate of rAAV-mediated BRCA1 KO. Approximately 35% of the selected cells
      were BRCA1 targeted. One BRCA1 KO cell clone (5D1), identified by PCR and
      Southern blot, was used as nuclear donor for HMC. Reconstructed embryos were
      transferred to three recipient sows which gave birth to 8 piglets in total.
      Genotyping identified seven piglets as BRCA1 heterozygotes (BRCA1(+/?11)), and
      one as wild type. The BRCA1 expression was decreased at the mRNA level in
      BRCA1(+/?11) fibroblasts. However, all BRCA1(+/?11) piglets died within 18 days
      after birth. The causes of perinatal mortality remain unclear. Possible
      explanations may include a combination of the BRCA1 haploinsufficiency, problems
      of epigenetic reprogramming, presence of the marker gene, single cell clone
      effects, and/or the special genetic background of the minipigs.

PMID- 21181440
TI  - Practice patterns in the use of anti-tumor necrosis factor alpha agents in the
      management of Crohn's disease: a US national practice survey comparing experts
      and non-experts.
AB  - BACKGROUND: The US Food and Drug Administration currently approves three types of
      anti-tumor necrosis factor alpha (anti-TNFalpha) therapy for treatment of
      moderate to severe Crohn's disease. There are no guidelines to clarify which of
      the drugs may be better suited to individual clinical scenarios. AIMS: We
      gathered national data on the prescribing pattern, comfort levels, and algorithms
      gastroenterologists use for management of their biologic-requiring Crohn's
      disease patients. METHODS: An internet survey was mailed to members of the
      American Gastroenterology Association. Responses were separated into "non-expert"
      and "expert" physician groups on the basis of whether a practice consisted of
      >50% of patients with inflammatory bowel disease. We compared experts with non
      experts with regard to the use of the three anti-TNF agents, attitudes regarding
      their relative efficacy, and their experience with adverse events. RESULTS: Of
      3,990 eligible gastroenterologists, 473 replied in full (11.9%). Sixty (12.6%)
      respondents met the criterion for IBD expert physician. Experts were comfortable
      using both immunomodulators and anti-TNFalpha therapy. Community physicians were
      equally comfortable prescribing 6-mercaptopurine, azathioprine, infliximab, and
      adalimumab, but less comfortable than experts with methotrexate (56 vs. 86%,
      P<0.05) and certolizumab (68 vs. 89%, P<0.05). Expert physicians were much more
      likely to have encountered adverse reactions to anti-TNFalpha therapy.
      CONCLUSIONS: Our results suggest that experts are more comfortable using a
      broader array of medical therapy than non-expert physicians. Although both groups
      had similar concerns regarding side-effects of anti-TNFalpha therapy, expert
      physicians were much more likely to have managed a broad range of complications
      in their patient population.

PMID- 21181441
TI  - Lubiprostone reverses the inhibitory action of morphine on mucosal secretion in
      human small intestine.
AB  - BACKGROUND AND AIMS: Treatments with morphine or opioid agonists cause
      constipation. Lubiprostone is approved for treatment of adult idiopathic
      constipation and constipation-predominant IBS in adult women. We tested whether
      lubiprostone can reverse morphine-suppression of mucosal secretion in human
      intestine and explored the mechanism of action. METHODS: Fresh segments of
      jejunum discarded during Roux-En-Y gastric bypass surgeries were used. Changes in
      short-circuit current (DeltaIsc) were recorded in Ussing flux chambers as a
      marker for electrogenic chloride secretion during pharmacological interactions
      between morphine, prostaglandin receptor antagonists, chloride channel blockers
      and lubiprostone. RESULTS: Morphine suppressed basal Isc. Lubiprostone reversed
      morphine suppression of basal Isc. Lubiprostone, applied to the mucosa in
      concentrations ranging from 3 nM to 30 MUM, evoked increases in Isc in
      concentration-dependent manner when applied to the mucosal side of muscle
      stripped preparations. Blockade of enteric nerves did not change stimulation of
      Isc by lubiprostone. Removal of chloride or application of bumetanide or NPPB
      suppressed or abolished responses to lubiprostone. Antagonists acting at CFTR
      channels and prostaglandin EP(4) receptors, but not at E(1), EP(1-3) receptors,
      partially suppressed stimulation of Isc by lubiprostone. CONCLUSIONS:
      Antisecretory action of morphine results from suppression of excitability of
      secretomotor neurons in the enteric nervous system. Lubiprostone, which does not
      affect enteric neurons directly, bypasses the action of morphine by directly
      opening mucosal chloride channels.

PMID- 21181442
TI  - Neural autoantibody evaluation in functional gastrointestinal disorders: a
      population-based case-control study.
AB  - BACKGROUND: Our goal is to investigate the serum profile of neural autoantibodies
      in community-based patients with irritable bowel syndrome (IBS) or functional
      dyspepsia. The pathogenesis of functional gastrointestinal (GI) disorders,
      including IBS and dyspepsia, are unknown. Theories range from purely
      psychological to autoimmune alterations in GI tract neuromuscular function.
      METHODS: The study subjects, based in Olmsted County, MN, reported symptoms of
      functional dyspepsia or IBS (n = 69), or were asymptomatic controls (n = 64).
      Their coded sera were screened for antibodies targeting neuronal, glial, and
      muscle autoantigens. RESULTS: The prevalence of neural autoantibodies with
      functional GI disorders did not differ significantly from controls (17% vs. 13%;
      P = 0.43). In no case was a neuronal or glial nuclear autoantibody or enteric
      neuronal autoantibody identified. Neuronal cation channel antibodies were
      identified in 9% of cases (voltage-gated potassium channel [VGKC] in one
      dyspepsia case and one IBS case, ganglionic acetylcholine receptor [AChR] in four
      IBS cases) and in 6% of controls (ganglionic AChR in one, voltage-gated calcium
      channel [VGCC], N-type, in two and VGKC in one; P = 0.36). The frequency of
      glutamic acid decarboxylase-65 (GAD65) autoantibodies was similar in cases (10%)
      and controls (5%; P = 0.23). CONCLUSIONS: Our data do not support neural
      autoimmunity as the basis for most IBS or functional dyspepsia cases.

PMID- 21181443
TI  - Apple sauce improves detection of esophageal motor dysfunction during high
      resolution manometry evaluation of dysphagia.
AB  - BACKGROUND: Esophageal manometry utilizes water swallows to evaluate esophageal
      motor abnormalities in patients with dysphagia, chest pain, or reflux symptoms.
      Although manometry is the gold standard for evaluation of these symptoms,
      patients with dysphagia often have normal results in manometry studies. AIM: The
      objective of this work was to test the hypothesis that challenging the esophagus
      with viscous apple sauce boluses uncovers motor abnormalities in patients with
      dysphagia not seen when using water swallows. METHODS: High-resolution esophageal
      manometry was performed using ten water swallows followed by ten apple sauce
      swallows in consecutive subjects presenting with dysphagia. Subjects with grossly
      abnormal water swallow evaluations were excluded. Each swallow was categorized as
      normal, hypotensive (distal isobaric contour plots of < 30 mmHg over >5 cm), or
      simultaneous (distal esophageal velocity >= 8.0 cm/s). Ineffective esophageal
      motility (IEM) was defined as >= 30% hypotensive swallows, and pressurization was
      defined as >= 20% simultaneous pressure waves. RESULTS: Data from 41 subjects was
      evaluated. Overall, 96.3% of water swallows were normal, 2.9% hypotensive, and
      0.7% simultaneous. Only 70.3% of viscous swallows were normal; 16.7% were
      hypotensive and 13.0% were simultaneous (P < 0.001 all groups). Seven (17.1%) met
      criteria for IEM, and pressurization with viscous swallows was observed for nine
      (22.0%). Fourteen subjects (34.1%) had abnormal results from viscous studies. The
      presence of any abnormal water swallows was predictive of abnormal viscous
      swallows (OR = 9.00, CI = 2.15-80.0), although the presence of hypotensive or
      simultaneous water swallows was not associated with IEM (OR = 0.63, CI = 0.16
      2.17) or pressurization (OR = 7.00, CI = 0.90-315.4) with viscous apple sauce.
      CONCLUSIONS: Apple sauce challenge increased identification of classifiable motor
      disorders in patients with dysphagia and may be preferred to alternative bolus
      materials.

PMID- 21181444
TI  - Role of cagA-positive Helicobacter pylori on cell proliferation, apoptosis, and
      inflammation in biliary cells.
AB  - BACKGROUND AND AIMS: The pathogenesis of Helicobacter pylori in the human
      hepatobiliary system has not been clearly elucidated. We compared the effects of
      H. pylori cagA(+) and cagA(-) mutant strains on cell proliferation, apoptosis,
      and inflammation in a cholangiocarcinoma (CCA) cell line (KKU-100). METHODS: MTT
      and BrdU were used to determine cell viability and DNA synthesis, respectively.
      The results were further investigated by RT-PCR and Western-blot analysis. The
      production of interleukin-8 (IL-8) was measured by ELISA assay. RESULTS: At low
      H. pylori inocula (cell-bacteria ratio of 1:1), the H. pylori cagA(+) strain
      showed a significant stimulation in KKU-100 cell growth (109 +/- 1.79%) and DNA
      synthesis (131 +/- 3.39%) than did the H. pylori cagA(-) strain (95 +/- 3.06% and
      120 +/- 2.32%, respectively), through activation of the anti-apoptotic bcl-2
      gene, MAP kinase and NF- kappaB cascade. By contrast, at high H. pylori inocula
      (cell-bacteria ratio of 1:200), the H. pylori cagA(+) strain showed a significant
      reduction in KKU-100 cell survival (49 +/- 2.47%) and DNA synthesis (49 +/-
      1.14%) than did the H. pylori cagA(-) strain (60 +/- 1.30% and 75 +/- 4.00%,
      respectively), by increased iNOS, p53 and bax, while decreased bcl-2.
      Additionally, caspase-8 and -3 protein were activated. The H. pylori cagA (+)
      strain had significantly stronger effect on IL-8 production than did the cagA(-)
      strain. CONCLUSIONS: These results suggest that the H. pylori cagA(+) strain may
      play an important role in the development of biliary cancer by disturbing cell
      proliferation, apoptosis, and promoting cell inflammation in the CCA cell line.

PMID- 21181445
TI  - Training community health workers about cancer clinical trials.
AB  - Innovative projects to reduce disparities in cancer treatment and research
      include partnerships between academic and community cancer centers, patient
      navigation programs and strategies to promote community awareness, education and
      engagement. A 4 h training program about cancer clinical trials was developed
      through a needs assessment and in collaboration with community health workers who
      served as consultants and a larger advisory board comprised of community health
      workers, educators and clinical trialists. This program was delivered first as a
      collaboration between a phsycian who is experienced in the conduct of clinical
      research and two community health workers, and subsequently by the community
      health workers alone. We report on four workshops attended by a total of 61
      community health workers recruited from Boston-area hospitals, community health
      centers and outreach programs. Support for and knowledge of clinical trials was
      measured in a pretest and post-test, which also included a satisfaction rating.
      Participants had a range of prior experience with clinical trials in the context
      of their personal and professional experience. Mean accuracy of knowledge about
      clinical trials increased from 72 to 84%, support for clinical trials improved
      considerably, and satisfaction with the training experience was high. Knowledge
      gaps and low levels of support for cancer clinical trials among community health
      workers can be improved with a short training program delivered by other
      community health workers. Further research is needed to identify the impact of
      this training on accrual to cancer clinical trials.

PMID- 21181446
TI  - Determinants of fasting plasma glucose and glycosylated hemoglobin among low
      income Latinos with poorly controlled type 2 diabetes.
AB  - The objective of this study was to identify demographic, socio-economic,
      acculturation, lifestyle, sleeping pattern, and biomedical determinants of
      fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c), among Latinos
      with type 2 diabetes (T2D). Latino adults (N = 211) with T2D enrolled in the
      DIALBEST trial were interviewed in their homes. Fasting blood samples were also
      collected in the participants' homes. Because all participants had poor glucose
      control, above-median values for FPG (173 mg/dl) and HbA1c (9.2%) were considered
      to be indicative of poorer glycemic control. Multivariate analyses showed that
      receiving heating assistance (OR: 2.20; 95% CI: 0.96-4.96), and having a radio
      (3.11, 1.16-8.35), were risk factors for higher FPG levels, and lower income
      (10.4, 1.54-69.30) was a risk factor for higher HbA1c levels. Lower carbohydrate
      intake during the previous day (0.04; 0.005-0.37), as well as regular physical
      activity (0.30; 0.13-0.69), breakfast (2.78; 1.10-6.99) and dinner skipping (3.9;
      1.03-14.9) during previous week were significantly associated with FPG
      concentrations. Being middle aged (2.24, 1.12-4.47), 30-60 min of sleep during
      the day time (0.07, 0.01-0.74) and having medical insurance (0.31, 0.10-0.96)
      were predictors of HbA1c. Results suggest that contemporaneous lifestyle
      behaviors were associated with FPG and contextual biomedical factors such as
      health care access with HbA1c. Lower socio-economic status indicators were
      associated with poorer FPG and HbA1c glycemic control.

PMID- 21181447
TI  - Race and preference-based health-related quality of life measures in the United
      States.
AB  - BACKGROUND: Health-related quality of life instruments (HRQoL) are widely used to
      produce measures that summarize population health and to inform decision-making
      and health policy. Although the literature about the relationship between health
      and race in the United States is quite extensive, there is a lack of studies that
      comprehensively examine the relationship between race and preference-based HRQoL.
      Given the widespread use of these measures, it becomes important to understand
      the extent of the race differences in HRQoL scores and factors associated with
      any such differences. METHODS: We examined the differences in HRQoL, between
      blacks and whites and associated factors, using the summary scores of the SF-6D,
      EQ-5D, QWB-SA, HUI2, HUI3, administered by telephone to a nationally
      representative sample of 3,578 black and white US adults between the ages of 35
      and 89 in the National Health Measurement Study (NHMS). RESULTS: Black women had
      substantially lower HRQoL than white women. The difference was largely explained
      by sociodemographic and socioeconomic variables. Black men did not differ
      significantly from white men, except for the EQ-5D. HRQoL among black men was
      higher at higher income levels, while the HRQoL of black women was especially low
      compared to other groups at high income levels.

PMID- 21181448
TI  - Microscopic bilateral posterior cordotomy in severe obstructive sleep apnea
      syndrome with bilateral vocal cord paralysis.
AB  - BACKGROUND: Vocal cord paralysis is a rare cause of obstructive sleep apnea
      syndrome (OSAS). Recurrent laryngeal nerve injury after thyroid gland surgery is
      one of the leading causes of acquired vocal cord paralysis. REPORT: A 46-year-old
      woman with OSAS due to bilateral abductor vocal cord paralysis was presented. She
      had thyroidectomy 30 years ago and had a weak, breathy voice. She had been
      referred with a history of high-pitched snoring, apnea witnessed by her spouse,
      and excessive daytime sleepiness for the last 5 years. Full-night polysomnography
      revealed that her apnea-hypopnea index was 72/h and minimal oxygen saturation
      level was 81%. There was no REM and deep sleep periods. Ear-nose-throat
      consultation offered an endoscopic bilateral posterior cordotomy operation via
      microscopic suspension laryngoscopy (MLS) as a treatment option. CONCLUSIONS:
      Instead of using a nasal positive airway pressure (nCPAP) device, she was treated
      surgically. Her OSAS resolved completely within 5 months of the surgery. Her
      phonation was preserved, and symptoms such as snoring and hypersomnolance
      disappeared. In OSAS patients with bilateral vocal cord paralysis, MLS-associated
      bilateral posterior cordotomy can be a choice of treatment as an alternative to
      nCPAP application.

PMID- 21181449
TI  - Case of atypical teratoid/rhabdoid tumor in an adult, with long survival.
AB  - Atypical teratoid/rhabdoid tumor (AT/RT) is a malignant tumor that mostly occurs
      in early childhood and has poor prognosis despite aggressive therapy. Adult cases
      are rare and, as far as we are aware, only 30 cases have been reported to date.
      Here we present the case of a 27-year-old female with left parietal AT/RT with
      the chief complaint of numbness of the right superior limb. First, the tumor was
      surgically removed and the diagnosis was grade II glioma. With additional
      radiotherapy, the clinical course after surgery was favorable. After 6 years, she
      had an operation for recurrence and the diagnosis was grade III glioma.
      Temozolomide was prescribed, and a disease-free period of 2 years followed.
      Surgery was performed for a third time for second recurrence with histology of
      diffuse growth of rhabdoid cells. Immunohistochemistry was partially positive for
      vimentin and epithelial membrane antigen. Ki-67 labeling index was extremely high
      and tumor cells showed no staining of INI1 suggestive of diagnosis of AT/RT. We
      re-evaluated past specimens and none had immunoreactivity of INI1. Ki-67 labeling
      index and O-6 methylguanine DNA methyltransferase (MGMT) staining were also re
      examined and both increased gradually. She is still alive without recurrence for
      more than 1 year. As far as we are aware, this is the second longest survival of
      an adult with AT/RT.

PMID- 21181450
TI  - Electrospun PLGA-silk fibroin-collagen nanofibrous scaffolds for nerve tissue
      engineering.
AB  - Electrospun nanofibrous scaffolds varying different materials are fabricated for
      tissue engineering. PLGA, silk fibroin, and collagen-derived scaffolds have been
      proved on good biocompatibility with neurons. However, no systematic studies have
      been performed to examine the PLGA-silk fibroin-collagen (PLGA-SF-COL)
      biocomposite fiber matrices for nerve tissue engineering. In this study,
      different weight ratio PLGA-SF-COL (50:25:25, 30:35:35) scaffolds were produced
      via electrospinning. The physical and mechanical properties were tested. The
      average fiber diameter ranged from 280 + 26 to 168 + 21 nm with high porosity and
      hydrophilicity; the tensile strength was 1.76 +/- 0.32 and 1.25 +/- 0.20 Mpa,
      respectively. The results demonstrated that electrospinning polymer blending is a
      simple and effective approach for fabricating novel biocomposite nanofibrous
      scaffolds. The properties of the scaffolds can be strongly influenced by the
      concentration of collagen and silk fibroin in the biocomposite. To assay the
      cytocompatibility, Schwann cells were seeded on the scaffolds; cell attachment,
      growth morphology, and proliferation were studied. SEM and MTT results confirmed
      that PLGA-SF-COL scaffolds particularly the one that contains 50% PLGA, 25% silk
      fibroin, and 25% collagen is more suitable for nerve tissue engineering compared
      to PLGA nanofibrous scaffolds.

PMID- 21181451
TI  - Improved bioprocess with CHO-hTSH cells on higher microcarrier concentration
      provides higher overall biomass and productivity for rhTSH.
AB  - Since the recombinant thyroid-stimulating hormone (rhTSH) is secreted by stably
      transfected Chinese hamster ovary (CHO-hTSH) cells, a bioprocess consisting of
      immobilizing the cells on a substrate allowing their multiplication is very
      suitable for rhTSH recovering from supernatants at relative high degree of
      purity. In addition, such a system has also the advantage of easily allowing
      delicate manipulations of culture medium replacement. In the present study, we
      show the development of a laboratory scale bioprocess protocol of CHO-hTSH cell
      cultures on cytodex microcarriers (MCs) in a 1 L bioreactor, for the preparation
      of rhTSH batches in view of structure/function studies. CHO-hTSH cells were
      cultivated on a fetal bovine serum supplemented medium during cell growth phase.
      For rhTSH synthesis phase, 75% of supernatant was replaced by animal protein-free
      medium every 24 h. Cell cultures were monitored for agitation (rpm), temperature
      ( degrees C), dissolved oxygen (% DO), pH, cell concentration, MCs coverage,
      glucose consumption, lactate production, and rhTSH expression. The results
      indicate that the amount of MCs in the culture and the cell concentration at the
      beginning of rhTSH synthesis phase were crucial parameters for improving the
      final rhTSH production. By cultivating the CHO-hTSH cells with an initial cell
      seeding of four cells/MC on 4 g/L of MCs with a repeated fed batch mode of
      operation at 40 rpm, 37  degrees C, 20% DO, and pH 7.2 and starting the rhTSH
      synthesis phase with 3 * 10(6) cells/mL, we were able to supply the cultures with
      enough glucose, to maintain low levels of lactate, and to provide high percent
      (~80%) of fully covered MCs for a long period (5 days) and attain a high cell
      concentration (~9 * 10(5) cells/mL). The novelty of the present study is
      represented by the establishment of cell culture conditions allowing us to
      produce ~1.6 mg/L of rhTSH in an already suitable degree of purity. Batches of
      produced rhTSH were purified and showed biological activity.

PMID- 21181452
TI  - Lymphangiography as a treatment method for chylous ascites following
      pancreaticoduodenectomy.

PMID- 21181454
TI  - Ischemic cerebrovascular stroke as complication of sepsis-induced Takotsubo
      cardiomyopathy.

PMID- 21181455
TI  - Rescuing the drowned: cardiopulmonary resuscitation and the origins of emergency
      medicine in the eighteenth century.
AB  - The concept of a medical emergency, i.e., a time when immediate action is
      required to stabilize and restore the vital functions, is absent in the tradition
      of ancient medicine, which seeks to cure the sick. The theoretical and conceptual
      development of a prompt medical assistance definitely owes much to the refinement
      of instruments and surgical techniques that were develop in the early modern age,
      allowing the extension of therapeutic action to "healthy" individuals who are
      suddenly life-threatened due to an accident or to some external events that
      affect their vital functions. But it is especially in the eighteenth century that
      the epistemic basis of medical emergency is structured, when the Enlightenment
      gave rise to the ethical and political imperative of public assistance that
      required the planning of first aid at multiple levels, and medicine developed the
      concept of life-saving treatment. In particular, eighteenth century medicine,
      studying systems to assure immediate relief to the victims of accidents
      especially to the drowned-allowed the development of specific and methodological
      systems of resuscitation and emergency treatment.

PMID- 21181456
TI  - Refolding by high pressure of a toxin containing seven disulfide bonds:
      bothropstoxin-1 from Bothrops jararacussu.
AB  - Aggregation is a serious obstacle for recovery of biologically active
      heterologous proteins from inclusion bodies (IBs) produced by recombinant
      bacteria. E. coli transformed with a vector containing the cDNA for Bothropstoxin
      1 (BthTx-1) expressed the recombinant product as IBs. In order to obtain the
      native toxin, insoluble and aggregated protein was refolded using high
      hydrostatic pressure (HHP). IBs were dissolved and refolded (2 kbar, 16 h), and
      the effects of protein concentration, as well as changes in ratio and
      concentration of oxido-shuffling reagents, guanidine hydrochloride (GdnHCl), and
      pH in the refolding buffer, were assayed. A 32% yield (7.6 mg per liter of
      bacterial culture) in refolding of the native BthTx-1 was obtained using optimal
      conditions of the refolding buffer (Tris-HCl buffer, pH 7.5, containing 3 mM of a
      2:3 ratio of GSH/GSSG, and 1 M GdnHCl). Scanning electron microscopy (SEM) showed
      that that disaggregation of part of IBs particles occurred upon compression and
      that the morphology of the remaining IBs, spherical particles, was not
      substantially altered. Dose-dependent cytotoxic activity of high-pressure
      refolded BthTx-1 was shown in C2C12 muscle cells.

PMID- 21181457
TI  - Surgical masks vs. N95 respirator masks for protecting health care professionals.

PMID- 21181458
TI  - Special issues in myeloproliferative neoplasms.
AB  - Special issues in myeloproliferative neoplasms (MPN) comprise clinical conditions
      with high relevance for the duration and quality of the patient's life, but with
      limited evidence to support sound diagnostic and therapeutic recommendations and
      a low probability of being solved by the current standard of clinical research.
      These issues include MPN in pregnancy and in children, abdominal vein thrombosis,
      bleeding complications, surgery, pruritus, and leukemic transformation. Practical
      suggestions to guide clinical decisions in these settings remain largely
      empirical, but recently developed guidelines based on experts' consensus may help
      to tackle these problems. This article reviews the state of the art regarding
      these issues, with special emphasis on experts' consensus recommendations.

PMID- 21181459
TI  - Speaking of one's life: what can we learn from transcultural studies?
AB  - The work by Demuth et al. (Integrative Psychological and Bahavioral Science 45:1
      20, 2011) is very important in the scenario of transcultural research, as it goes
      beyond the specific contexts of India and Germany. They successfully explored the
      dialogic relation between remembered autobiography, the self and the culture from
      a trans-generational development perspective, managing to identify common and
      unique processes of each culture. I, however, using a dynamical systems approach,
      present a supplementary way to the one chosen in the study, with the goal of
      analyzing how these new perspectives might contribute to the understanding of
      this phenomenon. The dynamical systems is a perspective sensitive to non
      linearity of phenomena and interested in understanding how processes emerge, as
      it may be useful to analyze the family as a dynamical system under constant
      interaction with other systems, which makes the emergence of the self, possible.
      Besides, it would enable the identification of trajectories that individuals
      build over time, the moments of change and variability, as well as identifying
      different types of patterns in the process of construction of the self.

PMID- 21181460
TI  - Does arthroscopic FAI correction improve function with radiographic arthritis?
AB  - BACKGROUND: Previous studies reporting the impact of osteoarthritis (OA) on pain
      and function after hip arthroscopy largely predate resection of femoroacetabular
      impingement (FAI). QUESTIONS/PURPOSES: We determined (1) functional improvement
      after resection of FAI impingement lesions in patients with preoperative
      radiographic joint space narrowing, and (2) identified preoperative predictors of
      pain, function, and failure rates in these patients. PATIENTS AND METHODS:
      Between September 2004 and April 2008, we treated 210 patients (227 hips) with
      FAI and a minimum 12-month followup (mean, 27 months). Group FAI consisted of 154
      patients (169 hips) without radiographic joint space narrowing, whereas Group FAI
      OA consisted of 56 patients (58 hips) with preoperative radiographic joint space
      narrowing. We collected Harris hip scores (HHS), Short Form-12 (SF-12), and pain
      scores on a visual analog scale (VAS) preoperatively and postoperatively.
      RESULTS: Score improvements were better for Group FAI compared with Group FAI-OA.
      The overall failure rate was greater for Group FAI-OA (52%) than for Group FAI
      (12%). Although patients with less than 50% joint space narrowing or greater than
      2 mm joint space remaining on preoperative radiographs had improved scores
      throughout the study, we observed no score improvements at any time with advanced
      preoperative joint space narrowing. Greater joint space narrowing, advanced MRI
      chondral grade, and longer duration of preoperative symptoms predicted lower
      scores. CONCLUSION: FAI correction with milder degrees of preoperative
      radiographic joint space narrowing resulted in improvements in pain and function
      at short-term followup. Patients with advanced radiographic joint space narrowing
      do not improve and we believe should not be considered for arthroscopic FAI
      correction.

PMID- 21181461
TI  - Dynamic changes in the cerebellar-interpositus/red-nucleus-motoneuron pathway
      during motor learning.
AB  - Understanding the role played by the cerebellum in the genesis and control of
      learned motor responses requires a precise knowledge of interdependent
      relationships between kinetic neural commands and the performance (kinematics) of
      the acquired movements. The eyelid motor system is a useful model for studying
      how simple motor responses are generated and performed. Here, we recorded the
      activity of interpositus, red nucleus, and/or facial motor neurons during
      classical eyeblink conditioning, using a delay paradigm. Experiments were carried
      out in behaving cats, and in conscious wild-type and (Purkinje cell devoid)
      Lurcher mice. Kinetic variables were determined by recording the firing
      activities of identified neurons at the mentioned nuclei, whilst kinematic
      variables were selected from the electromyographic activity of the orbicularis
      oculi muscle and/or from eyelid position recorded during the conditioned
      stimulus/unconditioned-stimulus interval. Whereas motoneurons encoded eyelid
      kinematics for acquired eyelid responses, interpositus, and red nucleus neurons
      did not directly encode eyelid performance, and the dynamic association between
      their neuronal activities was barely significant (from moderate to weak
      correlation, nonlinear coupling with high asymmetry, and neural firing activities
      that always lagged the beginning of the conditioned response). Nevertheless,
      interpositus and red nucleus neurons seem to play a modulating role in the
      dynamic control of this type of learned motor response, and present interesting
      adaptive properties in Lurcher mice. The analytical procedures proposed here
      could be very helpful in defining the functional state corresponding to each
      stage across the acquisition of new motor and cognitive abilities.

PMID- 21181462
TI  - Cerebellar internal models: implications for the dexterous use of tools.
AB  - Humans have remarkable abilities in the dexterous use of tools to extend their
      physical capabilities. Although previous neuropsychological and functional
      neuroimaging studies have mainly focused on the contribution of frontal-parietal
      cerebral networks to skills for tool use, dense anatomical and functional
      connections are known to exist between the frontal-parietal regions and the
      lateral cerebellum, suggesting that the cerebellum also supports the information
      processing necessary for the dexterous use of tools. In this article, we review
      functional and structural imaging studies reporting that the cerebellum is
      related to the learning acquisition of neural mechanisms representing input
      output properties of controlled objects, including tools. These studies also
      suggest that such mechanisms are modularly organized in the cerebellum
      corresponding to the different properties of objects, such as kinematic or
      dynamic properties and types of tools, and that they enable humans to flexibly
      cope with discrete changes in objects and environments by reducing interference
      and combining acquired modules. Based on these studies, we propose a hypothesis
      that the cerebellum contributes to the skillful use of tools by representing the
      input-output properties of tools and providing information on the prediction of
      the sensory consequences of manipulation with the parietal regions, which are
      related to multisensory processing, and information on the necessary control of
      tools with the premotor regions, which contribute to the control of hand
      movements.

PMID- 21181463
TI  - Oleic acid decreases the expression of a cholesterol transport-related protein
      (NPC1L1) by the induction of endoplasmic reticulum stress in CaCo-2 cells.
AB  - The reported data indicate that oleic acid (OA) decreases cholesterol absorption.
      To explore the underlying mechanisms, the effects of OA on the expression of
      cholesterol transport-related proteins (NPC1L1, ABCG5/8, ACAT2, MTP) and the
      unfolded protein response (UPR) pathway were studied in CaCo-2 enterocytes by
      incubating CaCo-2 cells with taurocholate micelles or taurocholate micelles
      containing different concentrations of OA (0.25-1.0 mM). We show that OA
      effectively induces XBP1 mRNA splicing, a key component of the UPR signaling, and
      the expression of BiP and mature ATF6 proteins in a concentration-dependent
      manner, leading to the induction of endoplasmic reticulum (ER) stress and
      activation of the UPR. Interestingly, OA decreases NPC1L1 expression in a dose
      dependent manner while it has no effects on ABCG5 and MTP mRNA level or SREBP-2,
      ABCG8, and ACAT2 protein level. In CaCo-2 cells treated with 1.0 mM OA, both the
      NPC1L1 mRNA level and the NPC1L1 protein expression in brush-border membrane
      fractions were decreased by 39% and 37%, respectively (P < 0.01). A dose of 1 mM
      dithiothreitol (DTT), a positive control for ER stress induction, also decreases
      NPC1L1 mRNA and protein expression by 27% and 23%, respectively (P < 0.05).
      Furthermore, 4-phenyl-butyric acid, an UPR inhibitor, blocks OA- and DTT-induced
      reduction on NPC1L1 mRNA and protein levels. The results suggest that OA down
      regulates NPC1L1 mRNA and protein expression via the induction of the UPR, which
      may play an important role in reducing intestinal cholesterol absorption.

PMID- 21181464
TI  - Clinicopathological characteristics and prognostic analysis of gastric cancer in
      the young adult in China.
AB  - The incidence of gastric cancer in young has increased steadily in the last
      decades. Little is known about the clinicopathologic features and prognostic
      factors of young adult gastric cancer patients. The clinicopathological
      characteristics of 294 young adult gastric cancer patients between 20 and 50
      years old were reviewed retrospectively from hospital records in Sun Yat-Sen
      University Cancer Center between 1996 and 2006. They were compared with 706 elder
      patients 51 years of age or over. A steady increasing in the proportion of female
      in the gastric carcinoma patients as the age decreasing was found. The
      distinguishing histological features of young adult patients were higher
      percentage of poorly differentiated grade and distant metastasis. The
      distribution of tumor-nodes-metastasis (TNM) stage was similar between these two
      groups. The 5-year disease-specific survival rate in the young adult group was
      significantly higher than in the elderly group. More patients receiving adjuvant
      chemotherapy were found in the young adult group. Multivariable analysis
      demonstrated that TNM stage and presence of angiolymphatic invasion were the
      independent negative predictors of survival for young patients with gastric
      cancer. Gastric cancer in young patients differs from that in elderly patients
      including a lack of male predilection, more aggressive histologic features, and
      better survival rate.

PMID- 21181465
TI  - Prognostic analysis in node-negative gastric cancer patients in China.
AB  - Gastric cancer patients with negative nodes were considered to have better
      outcomes, however, some of them still suffered from disease recurrences or
      distant metastases after radical resection. A total of 1,020 gastric carcinoma
      patients receiving treatment in our center between 2003 and 2008 were selected
      for the analysis. All patients received gastrectomy and D2 lymphadenectomy.
      Survival analysis was performed with Cox regression model. The final study
      includes 222 patients. The overall 5-year disease-specific survival rate was
      73.0%. Factors bearing significant association with lower survival on univariate
      analysis included the age of 58 years old or more (P = 0.021), tumor size longer
      than 4 cm (P < 0.001), presence of angiolymphatic invasion (P = 0.006), proximal
      site (P = 0.030), serosal invasion (T3+T4, P = 0.003), and higher TNM stage (P <
      0.001). Only three factors including serosal invasion, tumor size at least 4.0
      cm, and presence of angiolymphatic invasion remained independent negative
      predictors of survival in multivariable analysis. These parameters can be
      employed to select node-negative gastric cancer patients for an adjuvant setting
      and close follow-up scheduling.

PMID- 21181466
TI  - Mediterranean chemometrics.

PMID- 21181467
TI  - Improved method for plasma ADMA, SDMA, and arginine quantification by field
      amplified sample injection capillary electrophoresis UV detection.
AB  - Here, we describe an easy field-amplified sample injection capillary
      electrophoresis method with UV detection for the separation and detection of free
      plasma arginine and dimethylated arginines. The analytes were baseline-separated
      within 22 min by using 50 mmol/L Tris phosphate pH 2.3 as running buffer. The
      plasma samples were treated with acetonitrile/ammonia for protein elimination,
      the supernatants were dried, re-swollen in water and directly injected in the
      capillary without complex cleanup by solid phase extraction and/or tedious sample
      derivatization procedures. Due to the stacking effects of the electrokinetic
      injection, it was possible to operate a consistent on-line pre-concentration of
      the analytes before running the electrophoresis. This procedure allowed to reach
      a detection limit in the real sample of 10 nmol/L for dimethylated arginines and
      20 nmol/L for arginine, thus improving about threefold our previous method, that
      required a more complicated pre-analytical procedure to concentrate samples. The
      recovery of plasma ADMA was 99-104% and inter-day CV was less than 3%. The assay
      performance was evaluated measuring the levels of arginine and its dimethyl
      derivatives in 50 subjects. The statistical tests for the methods comparison
      suggest that the data obtained by our new method and by our previous CE assay are
      similar.

PMID- 21181468
TI  - Primary clear cell sarcoma of the sacrum: a case report.
AB  - Clear cell sarcoma, first described by Enzinger in 1965, is an uncommon malignant
      soft tissue neoplasm that displays melanocytic differentiation. It occurs
      predominantly in the soft tissue of the extremities in young adults or children.
      Primary clear cell sarcoma of the bone is extremely rare, only seven cases have
      been reported to our knowledge. We present here a case of a huge primary clear
      cell sarcoma of the sacrum arising in a 25-year-old man. The average percentage
      of melanin content in the tumor was 9.25 +/- 6.71%, which resulted in hypointense
      signal in T2-weighted and heterogeneous hyperintense signal in T1-wieghted images
      of magnetic resonance imaging (MRI). The patient was treated with curettage of
      the mass and neither further radiotherapy nor chemotherapy had been provided. The
      patient had local regrowth of tumor at 9 months after surgery. To our knowledge,
      this is the first case of CCS in the axial skeleton documented in English
      literature.

PMID- 21181469
TI  - Prognosis of patients with papillary thyroid carcinoma showing postoperative
      recurrence to the central neck.
AB  - BACKGROUND: The prognosis and prognostic factors of papillary carcinoma have been
      intensively investigated. However, details of patient prognosis after the
      detection of recurrence remain unclear. In this study, we investigated the
      prognosis of papillary carcinoma patients after showing recurrence in the central
      neck. METHODS: We enrolled 403 patients who underwent initial, locally curative
      surgery for papillary carcinoma in Kuma Hospital between 1987 and 2004 and then
      showed recurrence in the central neck during follow-up. RESULTS: The 5- and 10
      year cause-specific survival (CSS) rates for patients after initial recurrence to
      the lymph node were 95 and 88%, respectively. Age >45 years at recurrence and
      some clinicopathologic features at the initial surgery--aggressive histology,
      tumor >4 cm, lymph node metastasis >3 cm, significant extrathyroid extension-
      affected the CSS of patients. Except for extrathyroidal extension, these features
      were independent prognostic factors on a multivariate analysis. Patients
      initially showing recurrence to subcutaneous tissue suspected of needle tract
      implantation during fine-needle aspiration biopsy and those showing recurrence to
      the remnant thyroid demonstrated an excellent prognosis; none of these patients
      died of carcinoma during follow-up. The prognosis of patients showing initial
      recurrence to the thyroid bed or perithyroid tissue was significantly worse than
      that of those with initial recurrence to the lymph node; their 5- and 10-year CSS
      rates were 88 and 79%, respectively. CONCLUSIONS: Aggressive histology, the size
      of the primary lesion and of the lymph node metastasis, and age at recurrence
      independently affected the prognosis of patients showing initial recurrence to
      the lymph node. Prognoses of patients with recurrence to the subcutaneous tissue
      or remnant thyroid were excellent. However, patients initially showing recurrence
      to the thyroid bed or perithyroid tissue exhibited a worse prognosis; and careful
      second surgery and subsequent follow-up are thus mandatory.

PMID- 21181470
TI  - Unplanned conversion to thoracotomy during video-assisted thoracic surgery
      lobectomy does not compromise the surgical outcome.
AB  - BACKGROUND: Concerns remain unresolved regarding the safety of unplanned
      conversion to open thoracotomy during video-assisted thoracic surgery (VATS)
      lobectomy. We analyzed both early and late outcomes after thoracotomy conversion
      from VATS. METHODS: From December 2003 to December 2008, a total of 738 VATS
      lobectomies were attempted. Among them were 34 unplanned conversions to open
      thoracotomy. Patient characteristics, operative data, and early and late
      postoperative outcomes were analyzed retrospectively. RESULTS: Among the 34
      conversion cases, 26 patients had lung cancer and 8 had benign lung disease. The
      conversion rate was 4.61%. Left and right upper lobectomies were most often
      associated with unplanned conversions. Conversion was classified into five
      groups: (1) problems related to anthracofibrosis of hilar lymph nodes in 14
      patients; (2) intraoperative vessel or bronchus injury in 11 patients; (3) fused
      interlobar fissure in 4 patients; (4) oncologic problems, including mediastinal
      or hilar lymph node metastasis in 2 patients; and (5) vascular anomalies in 3
      patients. There was one death due to postoperative pneumonia in a patient with
      multiple co-morbidities. Two patients had an episode of pneumonia. The mean
      hospital stay was 10 days, and the median follow-up period was 30.0 +/- 11.47
      months. Three patients with lung cancer developed recurrent disease, all of whom
      were found to have stage III disease. No cancer-related death occurred. There was
      no significant difference in survival or recurrence between patients with
      conversion and those with successful VATS. However, the operating time and
      hospital stay were significantly longer in conversion patients. CONCLUSIONS: Our
      data support the claim that VATS lobectomy can be safely performed with an
      acceptable conversion rate. Unplanned conversion to open thoracotomy does not
      appear to compromise the prognosis.

PMID- 21181471
TI  - Mortality associated with the treatment of gallstone disease: a 10-year
      contemporary national experience.
AB  - BACKGROUND: Gallstones remain a common clinical problem requiring skilled
      operative and nonoperative management. The aim of the present population-based
      study was to investigate causes of gallstone-related mortality in Scotland.
      METHODS: Surgical deaths were peer reviewed between 1997 and 2006 through the
      Scottish Audit of Surgical Mortality (SASM); data were analyzed for patients in
      whom the principal diagnosis on admission was gallstone disease. RESULTS:
      Gallstone disease was responsible for 790/43,271 (1.83%) of the surgical deaths
      recorded, with an overall mortality for cholecystectomy of 0.307% (176/57,352),
      endoscopic retrograde cholangiopancreatography (ERCP) of 0.313% (117/37,345), and
      cholecystostomy of 2.1% (12/578) across the decade. However, the majority of
      patients who died were elderly (47.6% >= 80 years or older) and were managed
      conservatively. Deaths following cholecystectomy usually followed emergency
      admission (76%) and were more likely to have been associated with postoperative
      medical complications (n = 189) than surgical complications (n = 36). DISCUSSION:
      Although cholecystectomy is a relatively safe procedure, patients who die as a
      result of gallstone disease tend to be elderly, to have been admitted as
      emergency cases, and to have had co-morbidities. Future combined medical and
      surgical perioperative management may reduce the mortality rate associated with
      gallstones.

PMID- 21181472
TI  - Laparoscopic liver resection.
AB  - More than 3,000 laparoscopic liver resections (LLR) are performed worldwide for
      benign disease, malignancy, and living donor hepatectomy. Minimally invasive
      hepatic resection approaches include pure laparoscopic, hand-assisted
      laparoscopic, and a laparoscopic-assisted open "hybrid" approach, where the
      operation is started laparoscopically to mobilize the liver and begin the
      dissection, followed by a small laparotomy for completion of the parenchymal
      transection. Surgeons should have an advanced understanding of hepatic anatomy,
      extensive experience in open liver surgery, and technical skill to control major
      vascular and biliary structures laparoscopically before embarking on LLR.
      Although there is no absolute size criterion, smaller, peripheral lesions (<5 cm)
      that lie far from major vessels and anticipated transection planes are most
      amenable to LLR. Although the majority of reported LLR are non-anatomic
      resections or segmentectomies, several surgical groups are now performing
      laparoscopic major hepatic resections with excellent safety profiles. Patient
      benefits from LLR include less operative blood loss, less postoperative pain and
      narcotic requirement, and a shorter length of hospital stay, with comparable
      postoperative morbidity and mortality to open liver resection. Comparison studies
      between LLR and open resection have revealed no differences in width of resection
      margins for malignant lesions or overall survival after resection for
      hepatocellular cancer or colorectal cancer liver metastases. Advantages of LLR
      for HCC in particular include avoidance of collateral vessel ligation, decreased
      postoperative hepatic insufficiency, and fewer postoperative adhesions, all of
      which are features that enhance subsequent liver transplantation.

PMID- 21181473
TI  - Systematic review of prognostic factors related to overall survival in patients
      with stage IV colorectal cancer and unresectable metastases.
AB  - BACKGROUND: With the improvements in newer chemotherapeutic agents, the role of
      primary tumour resection in patients with stage IV colorectal cancer is
      controversial. In many cases primary tumour resection is still favoured as first
      line management. However, a detailed understanding of independent prognostic
      factors related to survival is necessary before making this decision. METHOD: A
      literature search was conducted using Medline and Embase. Studies that performed
      multivariate analysis on overall survival of patients with incurable stage IV
      colorectal cancer were included in this review. RESULTS: Fourteen retrospective
      studies involving 3209 patients were included. Clinical variables analysed to
      consistently have independent prognostic significance for long-term survival
      included the patients' performance status (<2), volume of liver metastases
      (<50%), nodal stage (N0), disease-free resection margins, and treatment with
      chemotherapy and/or primary tumour resection. Cancer antigen (CA) 19-9, low
      albumin, elevated ALP levels, apical lymph node involvement, presence of ascites,
      and postoperative transfusion were each assessed by only one study and found to
      be independently associated with survival. Factors inconsistently reported to
      have independent prognostic significance were age, ASA score, preoperative CEA
      levels, primary tumour location, tumour size and differentiation, peritoneal
      dissemination, and extrahepatic metastases. CONCLUSION: Each patient should be
      reviewed individually on the basis of the above independent prognostic factors
      before deciding to resect the primary tumour. Patients with a poor performance
      status, extensive hepatic metastases, and extensive nodal disease detected
      preoperatively are less likely to have a survival benefit. Nonsurgical approaches
      to manage these patients should be given careful consideration.

PMID- 21181474
TI  - Laparoscopic organ-sparing resection of von Hippel-Lindau disease-associated
      pancreatic neuroendocrine tumors.
AB  - BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are a characteristic feature
      of the tumor syndromes multiple endocrine neoplasia type 1 (MEN-1) and von Hippel
      Lindau disease (VHL). With VHL, about 10% of the patients exhibit PNETs by age 40
      years. Metastatic potential is high if the tumors have grown to >3 cm in
      diameter. Optimal surgical treatment is still a challenge. METHODS: We report
      three cases, all women, ages 22, 30, and 39 years, respectively, who had known
      VHL, confirmed by classic organ manifestations and germline mutations of the VHL
      gene. All were diagnosed, in an asymptomatic stage, with solid tumors of the
      pancreatic tail or tail/corpus area measuring 2.9-5.6 cm diameter. All accepted
      the offer of laparoscopic organ-sparing removal of the tumors. RESULTS: In all
      three cases, the tumor was entirely removed. In two cases, resection of the
      spleen was also necessary as dissection of the tumor from the major splenic
      vessels was impossible. Operating time was 215-365 min, and blood loss was 200
      700 ml. Histolopathology revealed benign PNETs in two cases, but the third
      patient had regional lymph node metastases. There were no complications, and the
      hospital stay was 4-7 days. CONCLUSIONS: Organ-sparing laparoscopic surgery is an
      important option for treating VHL-associated PNETs of the pancreatic tail.

PMID- 21181475
TI  - Weekly paclitaxel in patients with recurrent or metastatic head and neck cancer.
AB  - PURPOSE: To evaluate the efficacy and safety of weekly paclitaxel in patients
      with recurrent or metastatic head and neck cancer (HNC) by combined analysis of
      early and late phase II trials. METHODS: Eligibility criteria included
      histologically proven HNC with recurrent or metastatic disease, measurable
      disease, PS 0-2, and one or no prior chemotherapy regimens. Treatment consisted
      of a 1-h infusion of paclitaxel at a dose of 100 mg/m(2) weekly for 6 weeks of a
      7-week cycle. A total of 74 patients were enrolled: 37 between February and
      November 2004 in an early phase II trial and 37 between October 2005 and July
      2006 in a late phase II trial. RESULTS: The median number of treatment cycles was
      two, and median dose intensity was 84.2 mg/m(2)/week. The most common grade 3-4
      adverse events were leukopenia (37.5%), neutropenia (30.6%), anemia (12.5%),
      constipation (8.3%), peripheral neuropathy (5.6%), anorexia (5.6%), and
      pneumonitis (5.6%). Overall response rate was 29.0% according to RECIST. The
      median duration of response, median time to progression, and median survival time
      were 7.4, 3.4, and 14.3 months, respectively. CONCLUSIONS: This study
      demonstrates that weekly paclitaxel has promising activity with acceptable
      toxicity in the treatment of recurrent or metastatic HNC.

PMID- 21181476
TI  - Mechanisms of resistance to imatinib and sunitinib in gastrointestinal stromal
      tumor.
AB  - Gastrointestinal stromal tumor (GIST), the most common mesenchymal neoplasm of
      the GI tract and one of the most common sarcomas, is dependent on the expression
      of the mutated KIT or platelet-derived growth factor receptor in most cases.
      Imatinib mesylate potently abrogates the effects of KIT signaling by directly
      binding into the ATP-binding pocket of the kinase. It is becoming increasingly
      apparent that the binding affinity of imatinib for the receptor is dependent on
      the type and location of mutation. Within KIT, patients whose tumor has an exon 9
      mutation are treated by many clinicians with higher doses of imatinib than those
      patients with mutations within exon 11. Additionally, there are over 400 unique
      mutations within exon 11 that may have distinctly different binding affinity for
      imatinib as well as other kinases. Secondary KIT mutations generally occur at a
      codon where imatinib binds resulting in KIT reactivation and resistance.
      Sunitinib malate, a second-generation KIT inhibitor is active in imatinib
      resistant disease and is FDA-approved for use in this setting. In this review, we
      describe the biology of the genes and gene mutations responsible for GIST and
      discuss known and potential clinical implications.

PMID- 21181477
TI  - R132H-mutation of isocitrate dehydrogenase-1 is not sufficient for HIF-1alpha
      upregulation in adult glioma.

PMID- 21181478
TI  - Structural organization of the cerebral cortex of the neotropical lizard
      Tropidurus hispidus.
AB  - Lizards belonging to the Tropiduridae family are "sit-and-wait" foragers, relying
      mainly on visual identification to catch prey that cross their visual fields.
      Little is known about the neurobiology of Tropiduridae lizards. We have used
      neurohistological techniques to study the structural organization of the
      telencephalon of the neotropical lizard Tropidurus hispidus, paying special
      attention to the cerebral cortex. As revealed by the Nissl technique and Golgi
      staining, the telencephalon of T. hispidus follows the squamate pattern, with
      some differences: the lateral cortex appears relatively atrophic, and most of the
      neuronal somata of the dorsal cortex are dispersed without forming a conspicuous
      cell layer. Golgi staining has revealed ten different neuronal types in the three
      cortical layers, based on somata shape and dendritic morphology: the granular
      (unipolar, bipolar, and multipolar), pyramidal (normal, inverted, open,
      bipyramidal, and horizontal), spherical horizontal, and fusiform neuronal types.
      The axon direction could be traced in five of the subtypes. We have also studied
      the distribution of zinc-enriched terminals in the telencephalon of T. hispidus
      by the Neo-Timm method. Some portions of the cortex, septum, striatum, and
      amygdaloid complex stain heavily, with patterns resembling those described for
      other lizard families. Thus, T. hispidus appears to be an interesting
      representative of the Tropiduridae family for further neurobiological comparative
      studies.

PMID- 21181479
TI  - In vitro evaluation of a manganese chloride phantom-based MRI technique for
      quantitative determination of lumbar intervertebral disc composition and
      condition.
AB  - The application of MRI as a non-invasive, quantitative tool for diagnosing lumbar
      intervertebral disc degeneration is currently an area of active research. The
      objective of this study was to examine, in vitro, the efficacy of a manganese
      chloride phantom-based MRI technique for quantitatively assessing lumbar disc
      composition and degenerative condition. Sixteen human lumbar discs were imaged ex
      vivo using T2-weighted MRI, and assigned a quantitative grade based on the
      relative signal intensities of nine phantoms containing serial concentrations of
      manganese chloride. Discs were then graded macroscopically for degenerative
      condition, and water and uronic acid (glycosaminoglycan) contents were
      determined. MRI ranking exhibited significant and strong negative correlation
      with nucleus pulposus uronic acid content (r = -0.78). MRI grades were
      significantly higher for degenerate discs. The technique described presents
      immediate potential for in vitro studies requiring robust, minimally invasive and
      quantitative determination of lumbar disc composition and condition.
      Additionally, the technique may have potential as a clinical tool for diagnosing
      lumbar disc degeneration as it provides a standardised series of reference
      phantoms facilitating cross-platform consistency, requires short scan times and
      simple T2-weighted signal intensity measurements.

PMID- 21181480
TI  - Human mesenchymal stem cell co-culture modulates the immunological properties of
      human intervertebral disc tissue fragments in vitro.
AB  - The capacity of mesenchymal stem cells (MSCs) to differentiate into
      intervertebral disc (IVD)-like cells has been well described, but their ability
      to modulate the inflammatory processes in the IVD remains unclear. We found that
      tissue obtained by discectomy of degenerated and post-traumatic IVD contains
      significant amounts of IgG antibodies, a sign of lymphocyte infiltration. Further
      we investigated whether MSCs in vitro, which were characterized for their
      multilineage differentiation potential and may have immunomodulatory effects on
      IVD fragments. IVD fragments were co-cultured in contact with peripheral blood
      lymphocytes (PBLs) and MSCs, and as functional controls we used contact co
      cultures of PBLs stimulated with pokeweed mitogen (2.5 MUg/mL) and MSCs. The time
      course of lymphocyte proliferation (Alamar Blue), IgG (ELISA) and gene expression
      (RT-PCR) of anti-inflammatory cytokines (TGF-beta1, IL-10) by MSCs and pro
      inflammatory molecules (IL-1alpha, IL-1beta and TNF-alpha) by the IVD fragments
      were analyzed. Depending on the response to the presence of MSCs, the IVD
      fragments (n = 13) were divided in two groups: responders (n = 9), where
      inflammation was inhibited by MSCs and non-responders (n = 4), where MSCs did not
      decrease inflammation. At 1 week in co-culture, MSCs reduced significantly the
      IgG production in the IVD responders group to 69% and PBLs proliferation to 57%
      of the control. MSCs expression of the anti-inflammatory TGF-beta1 increased with
      time, while IL-10 was expressed only at day 1. IVD gene expression of TNF-alpha
      decreased constantly, whereas IL-1alpha and IL-1beta expression increased. In
      conclusion, these data suggest that MSCs may modulate disc-specific inflammatory
      and pain status and aid regeneration of the host tissue.

PMID- 21181481
TI  - Geometry of the vertebral bodies and the intervertebral discs in lumbar segments
      adjacent to spondylolysis and spondylolisthesis: pilot study.
AB  - The objective is to evaluate the geometric parameters of vertebral bodies and
      intervertebral discs in spinal segments adjacent to spondylolysis and
      spondylolisthesis. This pilot cross-sectional study was an ancillary project to
      the Framingham Heart Study. The presence of spondylolysis and spondylolisthesis
      as well as measurements of spinal geometry were identified on CT imaging of 188
      individuals. Spinal geometry measurements included lordosis angle, wedging of
      each lumbar vertebra and intervertebral disc. Last measurements were used to
      calculate SigmaB, the sum of the lumbar L1-L5 body wedge angles; and SigmaD, the
      sum of the lumbar L1-L5 intervertebral disc angles. Using Wilcoxon-Mann-Whitney
      test we compared the geometric parameters between individuals with no pathology
      and ones with spondylolysis (with no listhesis) at L5 vertebra, ones with isthmic
      spondylolisthesis at L5-S1 level, and ones with degenerative spondylolisthesis at
      L5-S1 level. Spinal geometry in individuals with spondylolysis or listhesis at L5
      shows three major patterns: In spondylolysis without listhesis, spinal morphology
      is similar to that of healthy individuals; In isthmic spondylolisthesis there is
      high lordosis angle, high L5 vertebral body wedging and very high L4-5 disc
      wedging; In degenerative spondylolisthesis, spinal morphology shows more lordotic
      wedging of the L5 vertebral body, and less lordotic wedging of intervertebral
      discs. In conclusion, there are unique geometrical features of the vertebrae and
      discs in spondylolysis or listhesis. These findings need to be reproduced in
      larger scale study.

PMID- 21181482
TI  - Pyogenic spondylitis in the elderly: a report from Japan with the most aging
      society.
AB  - Pyogenic spondylitis can be life-threatening for elderly patients. To discuss the
      characteristics of the disease in the elderly, medical records of 103 consecutive
      cases of pyogenic spondylitis were reviewed. Of these, 45 cases were 65 years of
      age or older, and these 45 cases were enrolled into further study. In this study,
      the proportion of elderly patients among the total number with pyogenic
      spondylitis was 43.7%, and this figure has increased with the passing of time as
      follows: 37.5% (1988-1993), 44.4% (1994-1999), and 55.5% (2000-2005). The
      microorganisms were isolated in 16 cases: Staphylococcus aureus in 13 cases
      (including methicillin-resistant Staphylococcus aureus in nine) and others in
      three. Twenty-five patients had associated diseases: diabetes in 18 patients and
      malignant tumors in seven. Thirty patients were treated conservatively, and 15
      patients underwent surgery. Twenty-six patients had paralysis. All 15 patients
      treated surgically, and eight of the 11 patients treated conservatively showed
      improvement in paralysis. Bone union was achieved in all cases except one. Our
      results indicate that a good outcome can be expected from conservative treatment
      in elderly patients as well as the young.

PMID- 21181483
TI  - Gait adaptations in low back pain patients with lumbar disc herniation: trunk
      coordination and arm swing.
AB  - Patients with chronic non-specific low back pain (LBP) walk with more synchronous
      (in-phase) horizontal pelvis and thorax rotations than controls. Low thorax
      pelvis relative phase in these patients appears to result from in-phase motion of
      the thorax with the legs, which was hypothesized to affect arm swing. In the
      present study, gait kinematics were compared between LBP patients with lumbar
      disc herniation and healthy controls during treadmill walking at different speeds
      and with different step lengths. Movements of legs, arms, and trunk were
      recorded. The patients walked with larger pelvis rotations than healthy controls,
      and with lower relative phase between pelvis and thorax horizontal rotations,
      specifically when taking large steps. They did so by rotating the thorax more in
      phase with the pendular movements of the legs, thereby limiting the amplitudes of
      spine rotation. In the patients, arm swing was out-of phase with the leg, as in
      controls. Consequently, the phase relationship between thorax rotations and arm
      swing was altered in the patients.

PMID- 21181484
TI  - X-ray absorption spectroscopy studies of the adducts formed between cytotoxic
      gold compounds and two major serum proteins.
AB  - Gold metallodrugs form a class of promising antiproliferative agents showing a
      high propensity to react with proteins. We exploit here X-ray absorption
      spectroscopy (XAS) methods [both X-ray absorption near-edge spectroscopy (XANES)
      and extended X-ray absorption fine structure (EXAFS)] to gain insight into the
      nature of the adducts formed between three representative gold(I, III)
      metallodrugs (i.e., auranofin, [Au(2,2'-bipyridine)(OH)(2)](PF(6)), Aubipy, and
      dinuclear [Au(2)(6,6'-dimethyl-2,2'-bipyridine)(2)(MU-O)(2)](PF(6))(2), Auoxo6)
      and two major plasma proteins, namely, bovine serum albumin (BSA) and human serum
      apotransferrin (apoTf). The following metallodrug-protein systems were
      investigated in depth: auranofin/apoTf, Aubipy/BSA, and Auoxo6/apoTf. XANES
      spectra revealed that auranofin, upon protein binding, conserves its gold(I)
      oxidation state. Protein binding most probably takes place through release of the
      thiosugar ligand and its subsequent replacement by a thiol (or a thioether) from
      the protein. This hypothesis is independently supported by EXAFS results. In
      contrast, the reactions of Aubipy with serum albumin and of Auoxo6 with serum
      apoTf invariantly result in gold(III) to gold(I) reduction. Gold(III) reduction,
      clearly documented by XANES, is accompanied, in both cases, by release of the
      bipyridyl ligands; for Auoxo6 cleavage of the gold-gold dioxo bridge is also
      observed. Gold(III) reduction leads to formation of protein-bound gold(I)
      species, with deeply modified metal coordination environments, as evidenced by
      EXAFS. In these adducts, the gold(I) centers are probably anchored to the protein
      through nitrogen donors. In general, these two XAS methods, i.e., XANES and
      EXAFS, used here jointly, allowed us to gain independent structural information
      on metallodrug/protein systems; detailed insight into the gold oxidation state
      and the local environment of protein-bound metal atoms was achieved in the
      various cases.

PMID- 21181485
TI  - Comparative study on dihydrofolate reductases from Shewanella species living in
      deep-sea and ambient atmospheric-pressure environments.
AB  - To examine whether dihydrofolate reductase (DHFR) from deep-sea bacteria has
      undergone molecular evolution to adapt to high-pressure environments, we cloned
      eight DHFRs from Shewanella species living in deep-sea and ambient atmospheric
      pressure environments, and subsequently purified six proteins to compare their
      structures, stabilities, and functions. The DHFRs showed 74-90% identity in
      primary structure to DHFR from S. violacea, but only 55% identity to DHFR from
      Escherichia coli (ecDHFR). Far-ultraviolet circular dichroism and fluorescence
      spectra suggested that the secondary and tertiary structures of these DHFRs were
      similar. In addition, no significant differences were found in structural
      stability as monitored by urea-induced unfolding and the kinetic parameters, K(m)
      and k(cat); although the DHFRs from Shewanella species were less stable and more
      active (2- to 4-fold increases in k(cat)/K(m)) than ecDHFR. Interestingly, the
      pressure effects on enzyme activity revealed that DHFRs from ambient-atmospheric
      species are not necessarily incompatible with high pressure, and DHFRs from deep
      sea species are not necessarily tolerant of high pressure. These results suggest
      that the DHFR molecule itself has not evolved to adapt to high-pressure
      environments, but rather, those Shewanella species with enzymes capable of
      retaining functional activity under high pressure migrated into the deep-sea.

PMID- 21181486
TI  - Molecular cloning, over expression and characterization of thermoalkalophilic
      esterases isolated from Geobacillus sp.
AB  - Due to potential use for variety of biotechnological applications, genes encoding
      thermoalkalophilic esterase from three different Geobacillus strains isolated
      from thermal environmental samples in Balcova (Agamemnon) geothermal site were
      cloned and respective proteins were expressed in Escherichia coli (E.coli) and
      characterized in detail. Three esterases (Est1, Est2, Est3) were cloned directly
      by PCR amplification using consensus degenerate primers from genomic DNA of the
      strains Est1, Est2 and Est3 which were from mud, reinjection water and
      uncontrolled thermal leak, respectively. The genes contained an open reading
      frame (ORF) consisting of 741 bp for Est1 and Est2, which encoded 246 amino acids
      and ORF of Est3 was 729 bp encoded 242 amino acids. The esterase genes were
      expressed in E. coli and purified using His-Select HF nickel affinity gel. The
      molecular mass of the recombinant enzyme for each esterase was approximately 27.5
      kDa. The three esterases showed high specific activity toward short chain p-NP
      esters. Recombinant Est1, Est2, Est3 have exhibited similar activity and the
      highest esterase activity of 1,100 U/mg with p-nitrophenyl acetate (pNPC(2)) as
      substrate was observed with Est1. All three esterase were most active around 65
      degrees C and pH 9.5-10.0. The effect of organic solvents, several metal ions,
      inhibitors and detergents on enzyme activity for purified Est1, Est2, Est3 were
      determined separately and compared.

PMID- 21181487
TI  - Medical decision-making system of ultrasound carotid artery intima-media
      thickness using neural networks.
AB  - The objective of this work is to develop and implement a medical decision-making
      system for an automated diagnosis and classification of ultrasound carotid artery
      images. The proposed method categorizes the subjects into normal,
      cerebrovascular, and cardiovascular diseases. Two contours are extracted for each
      and every preprocessed ultrasound carotid artery image. Two types of contour
      extraction techniques and multilayer back propagation network (MBPN) system have
      been developed for classifying carotid artery categories. The results obtained
      show that MBPN system provides higher classification efficiency, with minimum
      training and testing time. The outputs of decision support system are validated
      with medical expert to measure the actual efficiency. MBPN system with contour
      extraction algorithms and preprocessing scheme helps in developing medical
      decision-making system for ultrasound carotid artery images. It can be used as
      secondary observer in clinical decision making.

PMID- 21181488
TI  - Mercury resistance in Sporosarcina sp. G3.
AB  - Mercuric reductase (MerA) enzyme plays an important role in biogeochemical
      cycling and detoxification of Hg and recently, has also been shown to be useful
      in clean up of Hg-contaminated effluents. Present study describes isolation of a
      heavy metal-resistant isolate of Sporosarcina, which could tolerate up to 40,
      525, 210, 2900 and 370 MUM of Cd, Co, Zn, Cr and Hg respectively. It was found to
      reduce and detoxify redox-active metals like Cr and Hg. The chromate reductase
      and MerA activities in the crude cell extract of the culture were 1.5 and 0.044
      units/mg protein respectively. The study also describes designing of a new set of
      highly degenerate primers based on a dataset of 23 Firmicute merA genes. As the
      primers encompass the known diversity of merA genes within the phylum Firmicutes,
      they can be very useful for functional diversity analysis. They were successfully
      used to amplify a 787 bp merA fragment from the current isolate. A 1174 bp merA
      fragment was further cloned by designing an additional downstream primer. It was
      found to show 92% similarity to the putative merA gene from Bacillus cereus
      AH820. To the best of our knowledge, this is the first report of mercury
      resistance and merA gene sequence from Sporosarcina.

PMID- 21181489
TI  - Dimensionless parameters to summarize the influence of microbial growth and
      inhibition on the bioremediation of groundwater contaminants.
AB  - Monod expressions are preferred over zero- and first-order decay expressions in
      modeling contaminants biotransformation in groundwater because they better
      represent complex conditions. However, the wide-range of values reported for
      Monod parameters suggests each case-study is unique. Such uniqueness restricts
      the usefulness of modeling, complicates an interpretation of natural attenuation
      and limits the utility of a bioattenuation assessment to a small number of
      similar cases. In this paper, four Monod-based dimensionless parameters are
      developed that summarize the effects of microbial growth and inhibition on
      groundwater contaminants. The four parameters represent the normalized effective
      microbial growth rate (eta), the normalized critical contaminant/substrate
      concentration (S*), the critical contaminant/substrate inhibition factor (N), and
      the bioremediation efficacy (eta*). These parameters enable contaminated site
      managers to assess natural attenuation or augmented bioremediation at multiple
      sites and then draw comparisons between disparate remediation activities, sites
      and target contaminants. Simulations results are presented that reveal the
      sensitivity of these dimensionless parameters to Monod parameters and varying
      electron donor/acceptor loads. These simulations also show the efficacy of
      attenuation (eta*) varying over space and time. Results suggest electron
      donor/acceptor amendments maintained at relative concentrations S* between 0.5
      and 1.5 produce the highest remediation efficiencies. Implementation of the
      developed parameters in a case study proves their usefulness.

PMID- 21181490
TI  - Cometabolic biotransformation of fenpropathrin by Clostridium species strain ZP3.
AB  - A novel bacterial strain capable of degrading the pyrethroid pesticide
      fenpropathrin was isolated from mixed wastewater and sludge samples. Phylogenetic
      analysis of the 16S rDNA sequence revealed that the organism belongs to the genus
      Clostridium. The organism can co-metabolically transform fenpropathrin at 100 mg
      l(-1) at 35 degrees C and pH 7.5 in 12 days. Metabolic products of fenpropathrin
      from strain ZP3 were examined by gas chromatography/mass spectrometry, and the
      results showed that the organism degraded fenpropathrin with an oxidization
      process to yield benzyl alcohol, benzenemethanol, 3,5-dimethylamphetamine.
      Analyses of cell-free extracts from this strain showed that the optimal degrading
      conditions for degrading fenpropathrin were 35 degrees C and pH 7.5, and
      degradation efficiency was 20.0 mg l(-1) day(-1), and it might be potential using
      for rapid treating fenpropathrin, for example, on the surface of fruits and
      vegetables.

PMID- 21181491
TI  - Singular value decomposition based feature extraction technique for physiological
      signal analysis.
AB  - Multiscale entropy (MSE) is one of the popular techniques to calculate and
      describe the complexity of the physiological signal. Many studies use this
      approach to detect changes in the physiological conditions in the human body.
      However, MSE results are easily affected by noise and trends, leading to
      incorrect estimation of MSE values. In this paper, singular value decomposition
      (SVD) is adopted to replace MSE to extract the features of physiological signals,
      and adopt the support vector machine (SVM) to classify the different
      physiological states. A test data set based on the PhysioNet website was used,
      and the classification results showed that using SVD to extract features of the
      physiological signal could attain a classification accuracy rate of 89.157%,
      which is higher than that using the MSE value (71.084%). The results show the
      proposed analysis procedure is effective and appropriate for distinguishing
      different physiological states. This promising result could be used as a
      reference for doctors in diagnosis of congestive heart failure (CHF) disease.

PMID- 21181493
TI  - Investigating multitasking in high-functioning adolescents with autism spectrum
      disorders using the Virtual Errands Task.
AB  - Using a modified version of the Virtual Errands Task (VET; McGeorge et al. in
      Presence-Teleop Virtual Environ 10(4):375-383, 2001), we investigated the
      executive ability of multitasking in 18 high-functioning adolescents with ASD and
      18 typically developing adolescents. The VET requires multitasking (Law et al. in
      Acta Psychol 122(1):27-44, 2006) because there is a limited amount of time in
      which to complete the errands. ANCOVA revealed that the ASD group completed fewer
      tasks, broke more rules and rigidly followed the task list in the order of
      presentation. Our findings suggest that executive problems of planning
      inflexibility, inhibition, as well as difficulties with prospective memory
      (remembering to carry out intentions) may lie behind multitasking difficulties in
      ASD.

PMID- 21181494
TI  - Effect of Bt broccoli and resistant genotype of Plutella xylostella (Lepidoptera:
      Plutellidae) on development and host acceptance of the parasitoid Diadegma
      insulare (Hymenoptera: Ichneumonidae).
AB  - The ecological implications on biological control of insecticidal transgenic
      plants, which produce crystal (Cry) proteins from the soil bacterium Bacillus
      thuringiensis (Bt), remain a contentious issue and affect risk assessment
      decisions. In this study, we used a unique system of resistant insects, Bt plants
      and a parasitoid to critically evaluate this issue. The effects of broccoli type
      (normal or expressing Cry1Ac protein) and insect genotype (susceptible or Cry1Ac
      resistant) of Plutella xylostella L. (Lepidoptera: Plutellidae) were examined for
      their effects on the development and host foraging behavior of the parasitoid,
      Diadegma insulare (Cresson) (Hymenoptera: Ichneumonidae) over two generations.
      Parasitism rate and development of D. insulare were not significantly different
      when different genotypes (Bt-resistant or susceptible) of insect host larvae fed
      on non-Bt broccoli plants. D. insulare could not discriminate between resistant
      and susceptible genotypes of P. xylostella, nor between Bt and normal broccoli
      plants with different genotypes of P. xylostella feeding on them. No D. insulare
      could emerge from Bt broccoli-fed susceptible and heterozygous P. xylostella
      larvae because these larvae were unable to survive on Bt broccoli. The parasitism
      rate, developmental period, pupal and adult weights of D. insulare that had
      developed on Bt broccoli-fed Cry1Ac-resistant P. xylostella larvae were not
      significantly different from those that developed on non-Bt broccoli-fed larvae.
      Female D. insulare emerged from Cry1Ac-resistant P. xylostella that fed on Bt
      plants could successfully parasitize P. xylostella larvae. The life parameters of
      the subsequent generation of D. insulare from P. xylostella reared on Bt broccoli
      were not significantly different from those from non-Bt broccoli. The Cry1Ac
      protein was detected in P. xylostella and in D. insulare when hosts fed on Bt
      broccoli. These results are the first to indicate that Cry1Ac did not harm the
      development or host acceptance of an important endoparasitoid after two
      generations of exposure. We suggest that using other Bt crops and resistant
      insect species would likely lead to similar conclusions about the safety of the
      presently used Bt proteins on parasitoids.

PMID- 21181495
TI  - Breed and trait preferences of Sheko cattle keepers in southwestern Ethiopia.
AB  - Like their smallholder subsistence counterparts in developing countries, breed
      and trait preferences of Sheko cattle keepers have broad perspectives. Our study
      has documented breed and trait preferences of Sheko cattle keepers in
      southwestern Ethiopia--the natural breeding tract of Sheko cattle. Our results
      showed that due to their multifunctionality, cattle are the most preferred
      livestock species. Overall, farmers showed slightly more preference to local
      Zebus over Sheko breed. This is due to voracious feeding behavior of Sheko
      cattle, which make them less preferable in the face of worsening feed shortage,
      and due to aggressive temperament of Sheko cattle. This is despite Sheko's
      outperforming potential over local Zebus in their milk production, draft power,
      and hardiness. At trait level, overall milk production was consistently reported
      as the most preferred trait followed by fertility and traction. This trait
      preference rank has matched with the reported frequency count ranks for Sheko
      cattle use. However, breed preference rank has not matched with reported trait
      preference ranks because Sheko excels local Zebus in all the three most preferred
      traits, but it was ranked second. Therefore, to minimize these conflicting
      interests, breed management plans for Sheko cattle should target on strategies
      that help to solve feed shortage problem and to improve feeding practices, and on
      selection of less aggressive Sheko cattle. Therefore, these strategies should be
      considered in line with Sheko cattle conservation and genetic improvement
      programs.

PMID- 21181496
TI  - Use of multivariate analyses for determining heat tolerance in Brazilian cattle.
AB  - Adaptability can be evaluated by the ability of an animal to adjust to
      environmental conditions and is especially important in extreme weather
      conditions such as that found in tropical Brazil. A multivariate analysis using
      physical and physiological traits in exotic (Nellore and Holstein) and
      naturalized (Junqueira, Curraleira, Mocho Nacional, Crioula Lageana, and
      Pantaneira) cattle breeds was carried out in the Federal District of Brazil to
      test and determine which traits are important in the adaptation of animal to heat
      stress as well as the ability of these traits and statistical techniques to
      separate the breeds studied. Both physical and physiological traits were measured
      on three occasions and included body measurements, skin and hair thickness, hair
      number and length, pigmentation, sweat gland area as well as heart and breathing
      rates, rectal temperature, sweating rate, and blood parameters. The data
      underwent multivariate statistical analyses, including cluster, discriminate, and
      canonical procedures. The tree diagram showed clear distances between the groups
      studied, and canonical analysis was able to separate individuals in groups. Coat
      traits explained little variation in physiological parameters. The traits which
      had higher discriminatory power included packed cell volume, shoulder height,
      mean corpuscular volume, body length, and heart girth. Morphological and
      physiological traits were able to discriminate between the breeds tested, with
      blood and size traits being the most important. More than 80% of animals of all
      breeds were correctly classified in their genetic group.

PMID- 21181497
TI  - In vitro susceptibility of a large collection of Candida Strains against
      fluconazole and voriconazole by using the CLSI disk diffusion assay.
AB  - We evaluated all Candida spp. isolates obtained from patients admitted to two
      tertiary care hospitals between 1999 and 2003 in the city of Sao Paulo, Brazil.
      The in vitro activities of fluconazole (FCZ) and voriconazole were determined by
      the agar disk diffusion test using the Clinical and Laboratory Standards
      Institute M44-A guidelines. The inhibition zone diameters were read and
      interpreted automatically by the BIOMIC((r)) image-analysis plate reader system.
      We tested a total of 4,625 strains, including 2,393 strains of C. albicans
      (51.7%), 658 of C. tropicalis (14.2%), 503 of C. glabrata (10.9%), 495 of C.
      parapsilosis (10.7%), 292 of C. rugosa (6.3%), 195 of C. guilliermondii (4.2%)
      and 89 of other Candida species (2.0%). Only 2.0% of the strains tested were
      classified as dose-dependent susceptible (DDS), and 5.8% of them were resistant
      to FCZ. The resistance or DDS to fluconazole was verified mainly among C.
      glabrata (7.8%), C. krusei (67.9%) and C. rugosa (65.1%). Voriconazole exhibited
      better activity in vitro than fluconazole, even in isolates fluconazole
      resistant. The resistance of fluconazole and voriconazole did not increase in the
      isolates of Candida spp. during the evaluated period.

PMID- 21181498
TI  - Polymorphisms of caprine GDF9 gene and their association with litter size in
      Jining Grey goats.
AB  - The exons 1, 2 and flanking region of growth differentiation factor 9 (GDF9) gene
      in five randomly selected does of Jining Grey, Boer and Liaoning Cashmere goats
      were amplified and analyzed. Thirteen nucleotide differences were identified in
      GDF9 gene between sheep (AF078545) and goats. Four SNPs (G3288A in intron 1,
      G423A, A959C [Gln320Pro] and G1189A [Val397Ile] in exon 2) were detected in four
      goat breeds with different prolificacy, in which G3288A was a new SNP in goats.
      The results showed that loci 3288, 423 and 1189 in Boer goats, loci 3288 and 423
      in Guizhou White goats, loci 423 and 1189 in Liaoning Cashmere goats were all in
      complete linkage disequilibrium (D' = 1, r (2) = 1), respectively. In moderate
      (Boer goat) and low prolificacy (Liaoning Cashmere goat) breeds, linkage analysis
      indicated that there were more fervent linkage disequilibrium among loci 3288,
      423 and 1189 than high prolificacy (Jining Grey and Guizhou White goats) breeds.
      For the 959 locus, the genotype distribution showed obvious difference between
      high prolificacy breeds and moderate or low prolificacy breeds (P < 0.05 or P <
      0.01). The Jining Grey goat does with genotype CC or AC had 0.81 (P < 0.01) or
      0.63 (P < 0.01) kids more than those with genotype AA, respectively. The present
      study preliminarily showed an association between allele C at 959 locus of GDF9
      gene and high litter size in Jining Grey goats. These results provide further
      evidence that the GDF9 gene may be significantly correlated with high prolificacy
      in goats.

PMID- 21181499
TI  - Abscisic acid response element binding factor 1 is required for establishment of
      Arabidopsis seedlings during winter.
AB  - Abscisic acid (ABA) plays a crucial role in abiotic stress response apart from
      its influence on growth and development of a plant. Our studies on abscisic acid
      response element binding factor 1 (ABF1) gene in Arabidopsis demonstrate that it
      is required for seedling establishment during winter. ABF1 is also involved in
      regulating seed dormancy and seed germination to some extent. Analysis of
      transcriptional activity of ABF1 promoter reveals that ABF1 expresses
      specifically in trichomes of young leaves and constitutively in cotyledons,
      roots, older leaves and flowers. The expression is induced upon exposure to ABA,
      cold and heat. The alignment of cDNAs of ABF1 (At1g49720) and At1g49730 (encodes
      a protein kinase of unknown function), reveals an overlap of 88 bp at their 3'
      UTR region suggesting that they can potentially form natural cis-antisense mRNAs
      pair in a tail-to-tail manner. Analysis by Genevestigator microarray stress
      response viewer further supports the regulatory role of these genes. An inverse
      proportion is observed in the transcription the two loci in number of stress
      responses. The abf1 mutants do not show any seedling establishment defects when
      grown under standard growth conditions. The mutant seedlings exhibit growth
      defects during winter in the western Himalayan region. Our study also signifies
      the importance of functional analysis for mutant phenotypes in natural habitats
      by reverse genetic approaches, in order to identify specific function of
      particular gene/s whose expression level is altered upon exposure to changes in
      environmental cues such as temperature and light.

PMID- 21181500
TI  - Influence of maternal dental anxiety on oral health-related quality of life of
      preschool children.
AB  - PURPOSE: The aim of this study was to determine the influence of maternal dental
      anxiety on perceptions about oral health-related quality of life (OHRQoL) of
      preschool children. METHODS: A cross-sectional study was conducted with 608
      mother-child dyads during the Children's National Immunization Campaign in
      Pelotas, Brazil. Mothers answered a questionnaire on dental anxiety (DAS),
      socioeconomic status, use of dental services, and perception of their child's
      OHRQoL (ECOHIS). The ECOHIS includes a child impact section (symptoms, function,
      psychological, self-image/social interaction domains) and a family impact section
      (parent distress and family function domains). Clinical examination of the
      children was performed to assess dental caries, dental trauma, and occlusal
      traits occurrence. The association assessment used Poisson regression models (RR;
      95%CI, P <= 0.05). RESULTS: Anxious mothers presented higher scores in the parent
      distress domain. Higher impacts on OHRQoL were observed in children presenting
      untreated dental caries; children whose mothers had not completed primary
      education; and those who had non-regular use of dental services. CONCLUSIONS:
      Mean ECOHIS total score was not influenced by maternal dental anxiety. However,
      anxiety had a negative effect on the perception of the impact of the child's oral
      health problems in the family, affecting the parent distress domain.

PMID- 21181502
TI  - Local replicator dynamics: a simple link between deterministic and stochastic
      models of evolutionary game theory.
AB  - Classical replicator dynamics assumes that individuals play their games and adopt
      new strategies on a global level: Each player interacts with a representative
      sample of the population and if a strategy yields a payoff above the average,
      then it is expected to spread. In this article, we connect evolutionary models
      for infinite and finite populations: While the population itself is infinite,
      interactions and reproduction occurs in random groups of size N. Surprisingly,
      the resulting dynamics simplifies to the traditional replicator system with a
      slightly modified payoff matrix. The qualitative results, however, mirror the
      findings for finite populations, in which strategies are selected according to a
      probabilistic Moran process. In particular, we derive a one-third law that holds
      for any population size. In this way, we show that the deterministic replicator
      equation in an infinite population can be used to study the Moran process in a
      finite population and vice versa. We apply the results to three examples to shed
      light on the evolution of cooperation in the iterated prisoner's dilemma, on risk
      aversion in coordination games and on the maintenance of dominated strategies.

PMID- 21181501
TI  - Measuring tumor aggressiveness and targeting metastatic lesions with fluorescent
      pHLIP.
AB  - PURPOSE: Malignant cancer foci develop acidic extracellular environments. Mild
      acidic conditions trigger insertion and folding of the pH (low) insertion peptide
      (pHLIP(TM)) across a cellular membrane, enabling targeting of such lesions.
      PROCEDURES: We employed optical imaging to follow targeting by fluorescent pHLIP
      given i.v. in mice. For visualization, Cy5.5 and Alexa750 were covalently
      attached to the N terminus of pHLIP, which stays outside of a cell membrane after
      transmembrane insertion. RESULTS: We demonstrate that pHLIP targets: (a) tumors
      of different origins established by subcutaneous injection of cancer cells, (b)
      spontaneous prostate tumors in TRAMP mice and (c) metastatic lesions in lung
      pHLIP accumulation in tumors correlates with tumor aggressiveness. Within a
      tumor, it stains extracellular spaces and cellular membranes. CONCLUSIONS: Tissue
      acidity can be detected by pHLIP peptide insertion and used to diagnose primary
      tumors, metastatic lesions, and lipid bodies in necrotic tissues. The ability of
      pHLIP to differentially bind metastatic and non-metastatic tumors may provide a
      new approach for evaluating cancer prognosis.

PMID- 21181503
TI  - Experiments with the site frequency spectrum.
AB  - Evaluating the likelihood function of parameters in highly-structured population
      genetic models from extant deoxyribonucleic acid (DNA) sequences is
      computationally prohibitive. In such cases, one may approximately infer the
      parameters from summary statistics of the data such as the site-frequency
      spectrum (SFS) or its linear combinations. Such methods are known as approximate
      likelihood or Bayesian computations. Using a controlled lumped Markov chain and
      computational commutative algebraic methods, we compute the exact likelihood of
      the SFS and many classical linear combinations of it at a non-recombining locus
      that is neutrally evolving under the infinitely-many-sites mutation model. Using
      a partially ordered graph of coalescent experiments around the SFS, we provide a
      decision-theoretic framework for approximate sufficiency. We also extend a family
      of classical hypothesis tests of standard neutrality at a non-recombining locus
      based on the SFS to a more powerful version that conditions on the topological
      information provided by the SFS.

PMID- 21181504
TI  - Effective parameters determining the information flow in hierarchical biological
      systems.
AB  - Signaling networks are abundant in higher organisms. They play pivotal roles,
      e.g., during embryonic development or within the immune system. In this
      contribution, we study the combined effect of the various kinetic parameters on
      the dynamics of signal transduction. To this end, we consider hierarchical
      complex systems as prototypes of signaling networks. For given topology, the
      output of these networks is determined by an interplay of the single parameters.
      For different kinetics, we describe this by algebraic expressions, the so-called
      effective parameters.When modeling switch-like interactions by Heaviside step
      functions, we obtain these effective parameters recursively from the interaction
      graph. They can be visualized as directed trees, which allows us to easily
      determine the global effect of single kinetic parameters on the system's
      behavior. We provide evidence that these results generalize to sigmoidal Hill
      kinetics.In the case of linear activation functions, we again show that the
      algebraic expressions can be immediately inferred from the topology of the
      interaction network. This allows us to transform time-consuming analytic
      solutions of differential equations into a simple graph-theoretic problem. In
      this context, we also discuss the impact of our work on parameter estimation
      problems. An issue is that even the fitting of identifiable effective parameters
      often turns out to be numerically ill-conditioned. We demonstrate that this
      fitting problem can be reformulated as the problem of fitting exponential sums,
      for which robust algorithms exist.

PMID- 21181505
TI  - A symbolic investigation of superspreaders.
AB  - Superspreaders are an important phenomenon in the spread of infectious disease,
      accounting for a higher than average number of new infections in the population.
      We use mathematical models to compare the impact of supershedders and
      supercontacters on population dynamics. The stochastic, individual based models
      are investigated by conversion to deterministic, population level Mean Field
      Equations, using process algebra. The mean emergent population dynamics of the
      models are shown to be equivalent with and without superspreaders; however,
      simulations confirm expectations of differences in variability, having
      implications for individual epidemics.

PMID- 21181507
TI  - Agrobacterium-mediated silencing of caffeine synthesis through root
      transformation in Camellia sinensis L.
AB  - Tea [Camellia sinensis (L.) O. Kuntze] is a perennial and most popular non
      alcoholic caffeine-containing beverage crop. Tea has several constraints for its
      genetic improvement such as its high polyphenolic content and woody perennial
      nature. The development of transgenic tea is very difficult, laborious, and time
      taking process. In tea, regeneration requires minimum 8-12 months. In view of
      this, attempt has been made in this article to develop a rapid, efficient, and
      quite economical Agrobacterium-mediated root transformation system for tea. The
      feasibility of the developed protocol has been documented through silencing
      caffeine biosynthesis. For this, one-month-old tea seedlings were exposed to
      fresh wounding at the elongation zone of roots and were inoculated with
      Agrobacterium tumefaciens cultures carrying a RNAi construct (pFGC1008-CS). The
      pFGC1008-CS contained 376 bp of caffeine synthase (CS) cDNA fragment in sense and
      antisense direction with an intron in between. This has made the RNAi construct
      to produce a hairpin RNA (ihpRNA). The suppressed expression of CS gene and a
      marked reduction in caffeine and theobromine contents in young shoots of tea
      seedlings were obtained after root transformation through Agrobacterium
      infiltration. Such transformation system could be useful for functional analysis
      of genes in tea like woody and perennial plants.

PMID- 21181506
TI  - Atopic dermatitis and the nervous system.
AB  - Due to the narrow associations between the skin, immune system, and nervous
      system, nerve endings are very important in the pathophysiology of inflammatory
      dermatoses and especially in atopic dermatitis. Many neurotransmitters and nerve
      growth factors that are released in blood or skin are involved in neurogenic
      inflammation, which dramatically enhance the inflammation induced by immune
      cells. During times of stress, their release is highly enhanced. In atopic
      dermatitis lesions, there are many specific changes in skin neurobiology and
      neurophysiology. These interesting data suggest that novel therapeutic
      possibilities can be imagined.

PMID- 21181508
TI  - In vitro-in vivo correlation for gliclazide immediate-release tablets based on
      mechanistic absorption simulation.
AB  - The aim of this study was to develop a drug-specific absorption model for
      gliclazide (GLK) using mechanistic gastrointestinal simulation technology (GIST)
      implemented in GastroPlus(TM) software package. A range of experimentally
      determined, in silico predicted or literature data were used as input parameters.
      Experimentally determined pH-solubility profile was used for all simulations. The
      human jejunum effective permeability (P (eff)) value was estimated on the basis
      of in vitro measured Caco-2 permeability (literature data). The required PK
      inputs were taken from the literature. The results of the simulations were
      compared with actual clinical data and revealed that the GIST-model gave accurate
      prediction of gliclazide oral absorption. The generated absorption model provided
      the target in vivo dissolution profile for in vitro-in vivo correlation and
      identification of biorelevant dissolution specification for GLK immediate-release
      (IR) tablets. A set of virtual in vitro data was used for correlation purposes.
      The obtained results suggest that dissolution specification of more than 85% GLK
      dissolved in 60 min may be considered as "biorelevant" dissolution acceptance
      criteria for GLK IR tablets.

PMID- 21181509
TI  - Development of push-pull osmotic tablets using chitosan-poly(acrylic acid)
      interpolymer complex as an osmopolymer.
AB  - The objectives of this study were to prepare push-pull osmotic tablets (PPOT) of
      felodipine using an interpolymer complex of chitosan (CS) and poly(acrylic acid)
      (PAA) as an osmopolymer, and to study the mechanisms of drug release from these
      tablets. The interpolymer complexes were prepared with different weight ratios of
      CS to PAA. Preparation of PPOT involved the fabrication of bilayered tablets with
      the drug layer, containing felodipine, polyethylene oxide, and the polymeric
      expansion layer, containing the CS-PAA complex. The effects of polymer ratios,
      type of plasticizers, and compression forces on release characteristics were
      investigated. It was found that drug release from PPOT exhibited zero-order
      kinetics and could be prolonged up to 12 or 24 h depending on the plasticizer
      used. PPOT using dibutyl sebacate showed a longer lag time and slower drug
      release than that using polyethylene glycol 400. In the case of polyethylene
      glycol 400, an increase in the CS proportion resulted in an increase in the drug
      release rate. The compression force had no effect on drug release from PPOT. Drug
      release was controlled by two consecutive mechanisms: an osmotic pump effect
      resulting in the extrusion of the drug layer from the tablet and subsequent
      erosion and dissolution of the extruded drug layer in the dissolution medium. The
      mathematical model (zero-order) related to extrusion and erosion rates for
      describing the mechanism of drug release showed a good correlation between
      predicted and observed values.

PMID- 21181510
TI  - Development and evaluation of cetirizine HCl taste-masked oral disintegrating
      tablets.
AB  - The purpose of the current study was to mask the taste of cetirizine HCl and to
      incorporate the granules produced in oral disintegrating tablets (ODT). The
      bitter, active substance was coated by fluidized bed coating using Eudragit(r)
      RL30-D at levels between 15% and 40% w/w. The ODTs were developed by varying the
      ratio of superdisintegrants such as sodium croscarmellose, crospovidone grades
      and low substituted hydroxypropyl cellulose (L-HPC). A direct compression process
      was used to compress the ODTs under various compaction forces to optimize tablet
      robustness. The properties of the compressed tablets including porosity,
      hardness, friability and dissolution profiles were further investigated. The in
      vitro and in vivo evaluation of the tablet disintegration times showed almost
      identical rapid disintegration below 10 s at the optimal levels of each
      superdisintegrant. Finally, the taste and sensory evaluation in human volunteers
      demonstrated excellence in masking the bitter active and tablet palatability.

PMID- 21181511
TI  - Controlled release of oral tetrahydrocurcumin from a novel self-emulsifying
      floating drug delivery system (SEFDDS).
AB  - The objectives of this study were to develop and evaluate a novel self
      emulsifying floating drug delivery system (SEFDDS) that resulted in improved
      solubility, dissolution, and controlled release of the poorly water-soluble
      tetrahydrocurcumin (THC). The formulations of liquid self-emulsifying drug
      delivery system (SEDDS; mixtures of Labrasol, Cremophor EL, Capryol 90, Labrafac
      PG) were optimized by solubility assay and pseudo-ternary phase diagram analysis.
      The liquid SEDDS was mixed with adsorbent (silicon dioxide), glyceryl behenate,
      pregelatinized starch, sodium starch glycolate, and microcrystalline cellulose
      and transformed into pellets by the extrusion/spheronization technique. The
      resulting pellets with 22% liquid SEDDS had a uniform size and good self
      emulsification property. The microemulsions in aqueous media of different self
      emulsifying floating pellet formulations were in a particle size range of 25.9
      32.5 nm. Use of different weight proportions of glyceryl behenate and sodium
      starch glycolate in pellet formulations had different effects on the floating
      abilities and in vitro drug release. The optimum formulation (F2) had a floating
      efficiency of 93% at 6 h and provided a controlled release of THC over an 8-h
      period. The release rate and extent of release of THC liquid SEDDS (80% within 2
      h) and self-emulsifying floating pellet formulation (80% within 8 h) were
      significantly higher than that of unformulated THC (only 30% within 8 h). The
      pellet formulation was stable under intermediate and accelerated storage
      conditions for up to 6 months. Controlled release from this novel SEFDDS can be a
      useful alternative for the strategic development of oral solid lipid-based
      formulations.

PMID- 21181512
TI  - Optimization of process parameters for a quasi-continuous tablet coating system
      using design of experiments.
AB  - The aim of this study was to identify and optimize the critical process
      parameters of the newly developed Supercell quasi-continuous coater for optimal
      tablet coat quality. Design of experiments, aided by multivariate analysis
      techniques, was used to quantify the effects of various coating process
      conditions and their interactions on the quality of film-coated tablets. The
      process parameters varied included batch size, inlet temperature, atomizing
      pressure, plenum pressure, spray rate and coating level. An initial screening
      stage was carried out using a 2(6-1(IV)) fractional factorial design. Following
      these preliminary experiments, optimization study was carried out using the Box
      Behnken design. Main response variables measured included drug-loading
      efficiency, coat thickness variation, and the extent of tablet damage. Apparent
      optimum conditions were determined by using response surface plots. The process
      parameters exerted various effects on the different response variables. Hence,
      trade-offs between individual optima were necessary to obtain the best
      compromised set of conditions. The adequacy of the optimized process conditions
      in meeting the combined goals for all responses was indicated by the composite
      desirability value. By using response surface methodology and optimization,
      coating conditions which produced coated tablets of high drug-loading efficiency,
      low incidences of tablet damage and low coat thickness variation were defined.
      Optimal conditions were found to vary over a large spectrum when different
      responses were considered. Changes in processing parameters across the design
      space did not result in drastic changes to coat quality, thereby demonstrating
      robustness in the Supercell coating process.

PMID- 21181513
TI  - Quality by design and process analytical technology for sterile products--where
      are we now?
AB  - Quality by design (QbD) and process analytical technology (PAT) have become
      priorities for the Center for Drug Evaluation and Research (CDER) at the Food and
      Drug Administration (FDA). Numerous recent initiatives within CDER and FDA have
      had the objective of encouraging the pharmaceutical industry to utilize QbD and
      PAT in their product development and manufacturing processes. Although sterile
      products may be a minority compared to non-sterile dosage forms (e.g., solid
      orals), their absolute requirement for sterility make design and control of the
      manufacturing processes extremely critical. This emphasis on the manufacturing
      process makes the sterile drug product an obvious target for QbD and PAT.
      Although the FDA encourages QbD submissions, the utilization of QbD and PAT for
      sterile products so far is still limited. This paper will examine the present
      state of QbD and PAT for sterile products and review some examples currently in
      use. Additional potential applications of QbD and PAT for sterile product
      development and manufacturing will also be discussed.

PMID- 21181515
TI  - Stability models for sequential storage.
AB  - Some drugs are intended for sequential storage under two different storage
      conditions. If the data for each condition are analyzed separately, predicting
      assay and other responses after T1 months at one condition followed by T2 months
      at the other condition is non-trivial for several reasons. First, the two
      analyses will give different intercept terms. What should one do about that?
      Second, how would one calculate the confidence limits for combined storage?
      Third, what if prior storage at one condition affects the slope at the other
      condition? This paper proposes a simple ANCOVA model containing two slope terms,
      one for each storage condition. When multiple batches and/or packages are
      involved, it is easily generalized to two sets of slope terms. Confidence limits
      are straightforward and can be calculated using existing commercial software.
      With properly designed data, one can test whether prior storage at one condition
      affects the slope at the other condition. If no such effect is significant, very
      useful extrapolations can be made. Temperature excursions, model reduction and
      curvilinear dependencies are discussed.

PMID- 21181514
TI  - Comparison of spray freeze drying and the solvent evaporation method for
      preparing solid dispersions of baicalein with Pluronic F68 to improve dissolution
      and oral bioavailability.
AB  - The objective of this study was to prepare solid dispersions consisting of
      baicalein and a carrier with a low glass transition/melting point (Pluronic F68)
      by spray freeze drying (SFD). We compared these powders to those produced from
      the conventional solvent evaporation method. In the SFD process, a feeding
      solution was atomized above the surface of liquid nitrogen following
      lyophilization, which resulted in instantaneously frozen microparticles. However,
      solid dispersions prepared by the solvent evaporation method formed a sticky
      layer on the glass flask with crystalline baicalein separated out from the
      carrier. The powder samples were characterized by scanning electron microscopy
      (SEM), powder X-ray diffraction (PXRD), surface area measurement, differential
      scanning calorimetry, and Fourier transform infrared spectrometry. SEM and PXRD
      results suggested that the majority of baicalein in the SFD-processed solid
      dispersion was in the amorphous state, which has a higher specific surface area
      than pure baicalein. However, the majority of baicalein was recrystallized in the
      solid dispersion at the same composition prepared by the solvent evaporation
      method, which showed a similar dissolution rate to the physical mixture. SFD
      product was physically and chemically stable after being stored at 40  degrees C
      with low humidity for 6 months. After enzyme hydrolysis, baicalein in the SFD
      product displayed a significantly shorter T (max) and higher C (max) than pure
      baicalein after oral dosing. The relative bioavailability of the SFD product
      versus pure baicalein determined by comparing the AUC(0-12) was 233%, which
      demonstrated the significantly improved oral bioavailability of baicalein
      produced by the SFD technique.

PMID- 21181516
TI  - The manufacture of low-dose oral solid dosage form to support early clinical
      studies using an automated micro-filing system.
AB  - Automated powder dispensing systems enable supplying early clinical studies using
      drug-in-capsule approach, which is material sparing and requires a minimum amount
      of resources. However, the inability of accurately filling the capsule with a
      small amount, e.g., several micrograms, of drug limits the use of these systems
      for potent drugs. We demonstrate that formulated powder blends can be used to
      successfully fill capsules containing 5 MUg to 5 mg of drug with adequate content
      uniformity. Effective formulation and process strategies that enable this
      approach are presented with examples.

PMID- 21181517
TI  - Introduction to the special edition of keynote addresses and master lectures
      presented at the 2010 Annual Meeting of the Society of Behavioral Medicine.

PMID- 21181518
TI  - Depression and anxiety predict decline in physical health functioning in patients
      with heart failure.
AB  - BACKGROUND: Few studies have examined the prospective influences of depression
      and anxiety on physical health functioning in heart failure (HF) patients. Prior
      studies were also limited by employing psychological measures containing somatic
      items confounded with HF symptoms. PURPOSE: This study examined whether
      depression, anxiety, social support, and their changes predicted the decline of
      physical functioning in HF patients over 6 months. METHODS: Participants were 238
      HF patients among whom 164 provided follow-up data. The depression and anxiety
      measures did not contain somatic items. RESULTS: After controlling for baseline
      physical functioning and demographic and medical covariates, baseline depression
      and its increase, as well as baseline anxiety and its increase, independently
      predicted greater decline in physical functioning at 6 months. Social support and
      its change were not associated with either concurrent or follow-up physical
      functioning. CONCLUSIONS: Depression, anxiety, and their changes independently
      predicted the decline of physical health functioning over 6 months.

PMID- 21181520
TI  - Wide-beam reconstruction half-time SPECT improves diagnostic certainty and
      preserves normalcy and accuracy: a quantitative perfusion analysis.
AB  - BACKGROUND: Filtered back-projection (FBP) has been a standard in SPECT imaging.
      Newer iterative reconstruction algorithms have been shown to improve image
      quality and shorten acquisition time by taking into account statistical nature of
      raw data and using resolution recovery (RR). Wide-beam reconstruction (WBR) is an
      iterative algorithm with RR and adaptive noise control. We prospectively
      investigated outcome of WBR half-time SPECT on diagnostic certainty, accuracy and
      normalcy by quantitative perfusion analysis in comparison to full-time FBP
      images. METHODS: 434 patients underwent rest (201)Tl/stress (99m)Tc-sestamibi
      full-time (20 s/stop, FBP) followed by a half-time (10 s/stop, WBR) SPECT. 34
      patients underwent an angiogram within 90 days of SPECT. Diagnostic certainty was
      based on summed stress scores (SSS, 5-point/17 segments): normal if SSS <= 1,
      equivocal if SSS = 2-3, and abnormal if SSS >= 4. Perfusion defects were
      normalized to a percent of total myocardium, and expressed as %LV = defect
      SSS/maximal SSS * 100% with maximal SSS of 28 for left anterior descending (LAD),
      and of 20 for right coronary (RCA) and left circumflex (LCX). Change in %LV
      (Delta%LV = %LV FBP - %LV WBR) was evaluated for diagnostically discordant versus
      concordant scans. RESULTS: SSS and %LV demonstrated very good correlation. There
      were significantly fewer equivocal scans with WBR (38 vs 151 FBP, P < .0001).
      Most discordant scans were equivocal FBP SPECT becoming normal with WBR
      (123/151). Delta%LV(LAD) for discordant studies was greater for women (5.4% +/-
      4.2%, P < .001), while Delta%LV(RCA,LCX) (4.4% +/- 5.1%, P < .001; 1.2% +/- 5.0%,
      P = .04) were greater for men. Normalcy rate was 91.4% for FBP and WBR with more
      definitely normal WBR studies (84.5% vs 43.9% for FBP, P < .0001). There were no
      differences in sensitivity (FBP 84.2%, WBR 81.6%), specificity (FBP 54.6%, WBR
      63.6%), and accuracy (FBP, WBR 77.6%). CONCLUSION: Quantitative perfusion
      analysis suggests that adaptive noise control with WBR improves uniformity of
      myocardium comparing to FBP techniques, and results in improved diagnostic
      certainty while preserving normalcy and accuracy.

PMID- 21181519
TI  - The role of radionuclide myocardial perfusion imaging for asymptomatic
      individuals.

PMID- 21181522
TI  - Recent advances in plant transformation.
AB  - Plant genetic engineering has become one of the most important molecular tools in
      the modern molecular breeding of crops. Over the last decade, significant
      progress has been made in the development of new and efficient transformation
      methods in plants. Despite a variety of available DNA delivery methods,
      Agrobacterium- and biolistic-mediated transformation remain the two predominantly
      employed approaches. In particular, progress in Agrobacterium-mediated
      transformation of cereals and other recalcitrant dicot species has been quite
      remarkable. In the meantime, other transgenic-enabling technologies have emerged,
      including generation of marker-free transgenics, gene targeting, and chromosomal
      engineering. Although transformation of some plant species or elite germplasm
      remains a challenge, further advancement in transformation technology is expected
      because the mechanisms of governing the regeneration and transformation processes
      are now better understood and are being creatively applied to designing improved
      transformation methods or to developing new enabling technologies.

PMID- 21181521
TI  - Clinical, laboratory, and neuroimaging characteristics of fatigue in HIV-infected
      individuals.
AB  - Fatigue is among the most common symptoms reported by HIV-infected individuals.
      Previous reports suggest that the prevalence of fatigue varies by disease status
      with rates close to 80% in patients with AIDS. However, most studies have not
      been conducted in the setting of a controlled trial and have not assessed the
      association of fatigue with cellular markers of brain activity. Data for this
      study were derived from baseline and longitudinal evaluations in ACTG A5090, a
      randomized, double-blind, placebo-controlled trial of the Selegiline Transdermal
      System for the treatment of HIV-associated cognitive impairment. Fatigue was
      assessed using the Fatigue Severity Scale with scores of >4 considered
      "fatigued". Participants in a substudy underwent brain magnetic resonance
      spectroscopy (MRS) imaging, an in vivo method for assessing brain metabolites
      associated with neuronal and glia activity. Differences between fatigued and non
      fatigued participants were evaluated with respect to demographics and clinical
      characteristics, plasma and CSF HIV-1 RNA concentration, CD4 counts, and brain
      metabolites. One hundred and twenty-eight participants were enrolled (88% male,
      median age = 45 years) and 82 participants (64%, 95% confidence interval 55%,
      72%) were fatigued at baseline. MRS was conducted in 62 of the 128 participants.
      Fatigued participants were significantly younger (p = 0.011), had lower Karnofsky
      scores (p = 0.032), and had higher levels of depressive symptoms on the Center
      for Epidemiologic Studies Depression (CES-D) scale (p < 0.001) than non-fatigued
      participants. Statistically significant differences between fatigued and non
      fatigued groups were not detected for plasma and CSF HIV-1RNA concentration, CD4
      counts, or on neuropsychological tests. MRS revealed significantly lower levels
      of the cellular energy marker total creatine (p = 0.002) in the basal ganglia of
      fatigued participants. Statistically significant differences in other brain
      metabolites were not detected. Longitudinal data showed that fatigue persisted
      and worse fatigue at baseline was predictor of future fatigue. Among the
      cognitive tests, baseline Stroop score was associated with future fatigue.
      Fatigue was present in 64% of A5090 study participants and persisted during the
      24 weeks of follow-up. Fatigue was associated with worse functional performance
      and depressive mood. Lower cellular energy levels in the basal ganglia, as
      measured by MRS total creatine concentration, suggest energy dysmetabolism in
      this brain region. This observation, taken together with the association between
      fatigue and neuropsychological tests of frontal lobe performance is consistent
      with the hypothesis of a striatal-cortical circuitry involvement in the symptoms
      of fatigue.

PMID- 21181523
TI  - Engineering the plastid genome of Nicotiana sylvestris, a diploid model species
      for plastid genetics.
AB  - The plastids of higher plants have their own ~120-160-kb genome that is present
      in 1,000-10,000 copies per cell. Engineering of the plastid genome (ptDNA) is
      based on homologous recombination between the plastid genome and cloned ptDNA
      sequences in the vector. A uniform population of engineered ptDNA is obtained by
      selection for marker genes encoded in the vectors. Manipulations of ptDNA include
      (1) insertion of transgenes in intergenic regions; (2) posttransformation
      excision of marker genes to obtain marker-free plants; (3) gene knockouts and
      gene knockdowns, and (4) cotransformation with multiple plasmids to introduce
      nonselected genes without physical linkage to marker genes. Most experiments on
      plastome engineering have been carried out in the allotetraploid Nicotiana
      tabacum. We report here for the first time plastid transformation in Nicotiana
      sylvestris, a diploid ornamental species. We demonstrate that the protocols and
      vectors developed for plastid transformation in N. tabacum are directly
      applicable to N. sylvestris with the advantage that the N. sylvestris
      transplastomic lines are suitable for mutant screens.

PMID- 21181524
TI  - Homologous recombination in plants: an antireview.
AB  - Homologous recombination (HR) is a central cellular process involved in many
      aspects of genome maintenance such as DNA repair, replication, telomere
      maintenance, and meiotic chromosomal segregation. HR is highly conserved among
      eukaryotes, contributing to genome stability as well as to the generation of
      genetic diversity. It has been intensively studied, for almost a century, in
      plants and in other organisms. In this antireview, rather than reviewing existing
      knowledge, we wish to underline the many open questions in plant HR. We will
      discuss the following issues: how do we define homology and how the degree of
      homology affects HR? Are there any plant-specific HR qualities, how extensive is
      functional conservation and did HR proteins acquire new functions? How efficient
      is HR in plants and what are the cis and the trans factors that regulate it?
      Finally, we will give the prospects for enhancing the rates of gene targeting and
      meiotic HR for plant breeding purposes.

PMID- 21181526
TI  - Plant B chromosomes.
AB  - B chromosomes are dispensable elements of the genome that do not recombine with
      the A chromosomes of the regular complement and that follow their own
      evolutionary pathway. Here, we survey current knowledge on the DNA/chromatin
      composition, origin, and drive mechanisms of B chromosomes and discuss the
      potential research applications of supernumerary chromosomes.

PMID- 21181525
TI  - Chromosome painting for plant biotechnology.
AB  - Fluorescence in situ hybridization (FISH) is an invaluable tool for chromosome
      analysis and engineering. The ability to visually localize endogenous genes,
      transposable elements, transgenes, naturally occurring organellar DNA insertions 
      essentially any unique sequence larger than 2 kb - greatly facilitates progress.
      This chapter details the labeling procedures and chromosome preparation
      techniques used to produce high-quality FISH signals on somatic metaphase and
      meiotic pachytene spreads.

PMID- 21181527
TI  - Telomere truncation in plants.
AB  - Telomeres are highly repetitive sequences at the ends of chromosomes that act as
      protection structure for chromosome stability. The integration of telomere
      sequences into the genome by genetic transformation can create chromosome
      instability because the integrated telomere sequences tend to form de novo
      telomeres at the site of integration. Thus, telomere repeats can be used to
      generate minichromosomes by telomere-mediated chromosome truncation in both
      plants and animals for chromosome studies as well as the applications in genetic
      engineering as engineered minichromosomes or artificial chromosomes. This
      protocol describes the procedure for telomere truncation of maize chromosomes by
      genetic transformation of telomere-containing constructs by both Agrobacterium-
      and biolistic-mediated transformations.

PMID- 21181528
TI  - Engineered plant minichromosomes.
AB  - The advent of transgenic technologies has met many challenges, both technical and
      political; however, these technologies are now widely applied, particularly for
      crop improvement. Bioengineering has resulted in plants carrying resistance to
      herbicides, insects, and viruses, as well as entire biosynthetic pathways. Some
      of the technical challenges in generating transgenic plant or animal materials
      include: an inability to control the location and nature of the integration of
      transgenic DNA into the host genome, and linkage of transformed genes to
      selectable antibiotic resistance genes used in the production of the transgene
      cassette. Furthermore, successive transformation of multiple genes may require
      the use of several selection genes. The coordinated expression of multiple
      stacked genes would be required for complex biosynthetic pathways or combined
      traits. Engineered nonintegrating minichromosomes can overcome many of these
      problems and hold much promise as key players in the next generation of
      transgenic technologies for improved crop plants. In this review, we discuss the
      history of artificial chromosome technology with an emphasis on engineered plant
      minichromosomes.

PMID- 21181529
TI  - Method for Bxb1-mediated site-specific integration in planta.
AB  - Gene targeting in plants through homologous recombination has been sparsely
      reported, although notable breakthroughs have been achieved in recent years. In
      particular, the use of zinc finger nucleases to promote homologous end joining
      has revived the promise that homologous gene targeting could someday become
      practical for plant genetic engineering. An alternative and complementary
      approach that has progressed steadily over the years has been recombinase
      mediated site-specific integration. In this approach, a first recombination site
      is introduced into the genome to serve as a target for inserting subsequent DNA.
      Here, we describe the method for generating the chromosomal target and the
      subsequent insertion of new DNA into the chromosomal target by Bxb1-mediated site
      specific integration. This method would permit the comparison of different
      molecular constructs at the same genomic locations.

PMID- 21181530
TI  - Targeted mutagenesis in Arabidopsis using zinc-finger nucleases.
AB  - We report here an efficient method for making targeted mutations in Arabidopsis
      thaliana genes. The approach uses zinc-finger nucleases (ZFNs) - enzymes
      engineered to create DNA double-strand breaks at specific target loci. Imprecise
      repair of double-strand breaks by nonhomologous end-joining generates small
      insertions or deletions at the cleavage site. In this protocol, constructs
      encoding ZFNs for specific loci are transformed into Arabidopsis by Agrobacterium
      mediated transformation. ZFN expression is induced during germination to initiate
      mutagenesis of the target locus. Typically, more than 20% of the primary
      transgenics segregate loss-of-function mutations in the next generation. ZFNs
      make it possible to expand the range of Arabidopsis mutants available for study
      and to create mutations in genes missed by random mutagenesis approaches, such as
      those using T-DNA, transposons, or chemical mutagens.

PMID- 21181531
TI  - Vectors and methods for hairpin RNA and artificial microRNA-mediated gene
      silencing in plants.
AB  - In plant cells, DICER-LIKE4 processes perfectly double-stranded RNA (dsRNA) into
      short interfering (si) RNAs, and DICER-LIKE1 generates micro (mi) RNAs from
      primary miRNA transcripts (pri-miRNA) that form fold-back structures of
      imperfectly dsRNA. Both si and miRNAs direct the endogenous endonuclease,
      ARGONAUTE1 to cleave complementary target single-stranded RNAs and either small
      RNA (sRNA)-directed pathway can be harnessed to silence genes in plants. A
      routine way of inducing and directing RNA silencing by siRNAs is to express self
      complementary single-stranded hairpin RNA (hpRNA), in which the duplexed region
      has the same sequence as part of the target gene's mRNA. Artificial miRNA
      (amiRNA)-mediated silencing uses an endogenous pri-miRNA, in which the original
      miRNA/miRNA* sequence has been replaced with a sequence complementary to the new
      target gene. In this chapter, we describe the plasmid vector systems routinely
      used by our research group for the generation of either hpRNA-derived siRNAs or
      amiRNAs.

PMID- 21181532
TI  - Recombinant protein expression in Nicotiana.
AB  - Recombinant protein pharmaceuticals are now widely used in treatment of chronic
      diseases, and several recombinant protein subunit vaccines are approved for human
      and veterinary use. With growing demand for complex protein pharmaceuticals, such
      as monoclonal antibodies, manufacturing capacity is becoming limited. There is
      increasing need for safe, scalable, and economical alternatives to mammalian cell
      culture-based manufacturing systems, which require substantial capital investment
      for new manufacturing facilities. Since a seminal paper reporting immunoglobulin
      expression in transgenic plants was published in 1989, there have been many
      technological advances in plant expression systems to the present time where
      production of proteins in leaf tissues of nonfood crops such as Nicotiana species
      is considered a viable alternative. In particular, transient expression systems
      derived from recombinant plant viral vectors offer opportunities for rapid
      expression screening, construct optimization, and expression scale-up. Extraction
      of recombinant proteins from Nicotiana leaf tissues can be achieved by collection
      of secreted protein fractions, or from a total protein extract after grinding the
      leaves with buffer. After separation from solids, the major purification
      challenge is contamination with elements of the photosynthetic complex, which can
      be solved by application of a variety of facile and proven strategies. In
      conclusion, the technologies required for safe, efficient, scalable manufacture
      of recombinant proteins in Nicotiana leaf tissues have matured to the point where
      several products have already been tested in phase I clinical trials and will
      soon be followed by a rich pipeline of recombinant vaccines, microbicides, and
      therapeutic proteins.

PMID- 21181533
TI  - Chromosome analysis and sorting using flow cytometry.
AB  - Chromosome analysis and sorting using flow cytometry (flow cytogenetics) is an
      attractive tool for fractionating plant genomes to small parts. The reduction of
      complexity greatly simplifies genetics and genomics in plant species with large
      genomes. However, as flow cytometry requires liquid suspensions of particles, the
      lack of suitable protocols for preparation of solutions of intact chromosomes
      delayed the application of flow cytogenetics in plants. This chapter outlines a
      high-yielding procedure for preparation of solutions of intact mitotic
      chromosomes from root tips of young seedlings and for their analysis using flow
      cytometry and sorting. Root tips accumulated at metaphase are mildly fixed with
      formaldehyde, and solutions of intact chromosomes are prepared by mechanical
      homogenization. The advantages of the present approach include the use of
      seedlings, which are easy to handle, and the karyological stability of root
      meristems, which can be induced to high degree of metaphase synchrony.
      Chromosomes isolated according to this protocol have well-preserved morphology,
      withstand shearing forces during sorting, and their DNA is intact and suitable
      for a range of applications.

PMID- 21181534
TI  - Super-stretched pachytene chromosomes for plant molecular cytogenetic mapping.
AB  - We developed a simple technique to mechanically stretch maize pachytene
      chromosomes more than 20 times longer than their original size. A modified
      Carnoy's II solution (6:3:1) ethanol:acetic acid:chloroform was used to fix the
      meiotic sample. The super-stretched pachytene chromosomes produced from this
      procedure can be directly used in conventional fluorescence in situ hybridization
      (FISH) experiments and also for the immunofluorescent in situ detection of DNA
      methylation. This technique adds a new dimension and higher resolving power to
      pachytene chromosome-based molecular cytogenetics research.

PMID- 21181535
TI  - Cytological dissection of the triticeae chromosomes by the gametocidal system.
AB  - Triticeae species have a large and complex genome, which has made it difficult to
      obtain their sequence data. Some alien chromosomes called the gametocidal (Gc)
      chromosomes introduced into common wheat can induce chromosomal breakage
      resulting in the generation of deletions and translocations. The induced
      deletions have been established as deletion stocks in common wheat. This Gc
      system is also effective in inducing chromosomal breakages in Triticeae
      chromosomes added to common wheat. The induced aberrant chromosomes can be
      identified by chromosome banding and fluorescence in situ hybridization and can
      be established in common wheat as dissection lines. This Gs system will be useful
      to dissect the single chromosomes of Triticeae species.

PMID- 21181536
TI  - Development and use of oat-maize chromosome additions and radiation hybrids.
AB  - Hybridization experiments of oat with maize require fastidious coordination of
      plant cultivation and flowering timing, meticulous crossing techniques,
      stimulation with plant growth substances, and in vitro rescue and culture of the
      hybrid embryos. The majority of hybrid offspring gradually lose all maize
      chromosomes consequently resulting in haploid oat plants. However, a minority of
      the offspring retain one or more maize chromosome(s) in addition to their haploid
      oat complements (partial hybrids). Oat haploids and partial hybrids with 1-3
      maize chromosomes are partially fertile. Controlled self-fertilization of partial
      hybrids allows for the production of doubled haploid oat plants with an added
      single maize chromosome (monosomic addition) or an added pair of homologous maize
      chromosomes (disomic addition) among the inbred offspring. gamma-Irradiation of
      monosomic oat-maize addition lines can be used to further dissect the maize
      chromosome in a given line. The lines with identified maize chromosome fragments
      (radiation hybrids) are the basis for establishing chromosome-specific panels.
      Although still in the experimental phase, the use of radiation hybrids has been
      useful and has widened the repertoire of maize genetics and genomics methodology.

PMID- 21181537
TI  - Enhancer trapping in plants.
AB  - Advances in sequencing technology have led to the availability of complete genome
      sequences of many different plant species. In order to make sense of this deluge
      of information, functional genomics efforts have been intensified on many fronts.
      With improvements in plant transformation technologies, T-DNA and/or transposon
      based gene and enhancer-tagged populations in various crop species are being
      developed to augment functional annotation of genes and also to help clone
      important genes. State-of-the-art cloning and sequencing technologies, which
      would help identify T-DNA or transposon junction sequences in large genomes, have
      also been initiated. This chapter gives a brief history of enhancer trapping and
      then proceeds to describe gene and enhancer tagging in plants. The significance
      of reporter gene fusion populations in plant genomics, especially in important
      cereal crops, is discussed.

PMID- 21181538
TI  - Chromatin beacons: global sampling of chromatin physical properties using
      chromatin charting lines.
AB  - The extent to which physical properties and intranuclear locations of chromatin
      can influence transcription output remains unclear and poorly quantified. Because
      the scale and resolution at which structural parameters can be queried are
      usually so different from the scale that transcription outputs are measured, the
      integration of these data is often indirect. To overcome this limitation in
      quantifying chromatin structural parameters at different locations in the genome,
      a Chromatin Charting collection with 277 transposon-tagged Arabidopsis lines has
      been established in order to discover correlations between gene expression and
      the physical properties of chromatin loci within the nuclei. In these lines,
      dispersed loci in the Arabidopsis genome are tagged with an identical transgene
      cassette containing a luciferase gene reporter, which permits the quantification
      of gene expressions in real time, and an ~2 kb LacO repeat that acts as a
      "chromatin beacon" to facilitate the visual tracking of a tagged locus in living
      plants via the expression of LacI-GFP fusion proteins in trans. In this chapter,
      we describe the methods for visualizing and tracking these insertion loci in vivo
      and illustrate the potential of using this approach to correlate chromatin
      mobility with gene expression in living plants.

PMID- 21181539
TI  - Transposable elements as catalysts for chromosome rearrangements.
AB  - Barbara McClintock first showed that transposable elements in maize can induce
      major chromosomal rearrangements, including duplications, deletions, inversions,
      and translocations. More recently, researchers have made significant progress in
      elucidating the mechanisms by which transposons can induce genome rearrangements.
      For the Ac/Ds transposable element system, rearrangements are generated when the
      termini of different elements are used as substrates for transposition. The
      resulting alternative transposition reaction directly generates a variety of
      rearrangements. The size and type of rearrangements produced depend on the
      location and orientation of transposon insertion. A single locus containing a
      pair of alternative transposition-competent elements can produce a virtually
      unlimited number of genome rearrangements. With a basic understanding of the
      mechanisms involved, researchers are beginning to utilize both naturally
      occurring and in vitro-generated configurations of transposable elements in order
      to manipulate chromosome structure.

PMID- 21181540
TI  - Serological markers can lead to false negative diagnoses of periprosthetic
      infections following total knee arthroplasty.
AB  - Periprosthetic infections following total knee arthroplasty (TKA) are
      diagnostically challenging. We evaluated the sensitivity and specificity of ESR
      and CRP, false negative rates, whether false negative rates differed between
      early post-operative and late infections, and the predictive ability of ESR and
      CRP to differentiate infected patients. Between 2000 and 2007, a prospectively
      collected database was reviewed to identify patients with suspected
      periprosthetic infections, and who had ESR and CRP laboratory values. One hundred
      and thirteen patients were identified. False negative rates were calculated.
      Finally, receiver operating characteristic curves were used to determine the
      predictive ability of ESR and CRP to differentiate infected from non-infected
      patients. CRP had a sensitivity of 95% and specificity of 20%. ESR had a
      sensitivity of 91% and a specificity of 33%. The false negative rate was 9.2% for
      ESR, 5.3% for CRP, and 11.1% for combined ESR and CRP. False negative rates were
      higher for early post-operative infections. Although ESR and CRP can be excellent
      adjunctive diagnostic tools, we emphasise that because some patients may not
      mount a sufficient immune response, the entire clinical picture must be
      evaluated, and periprosthetic infection should not be ruled out on the basis of
      ESR and CRP results alone.

PMID- 21181541
TI  - Aphasia assessment and functional outcome prediction in patients with aphasia
      after stroke.
AB  - Available studies did not clarify whether a language examination may predict
      functional and motor outcome in patients with aphasia undergoing rehabilitation.
      This was the aim of the current study. Language examination considered in this
      study was the Aachen Aphasia Test (AAT). One hundred fifty-six patients with a
      primary diagnosis of acute cerebrovascular accident of left hemisphere were
      included: 105 with and 51 without aphasia. Backward stepwise regression analysis
      was used to predict final scores in total-, motor-, and cognitive-Functional
      Independence Measure (FIM). The independent variables were age, gender, stroke
      type, stroke lesion size, onset to admission interval, National Institute of
      Health Stroke Scale, Fugl-Meyer Scale, Trunk Control Test, initial motor-FIM, and
      AAT (spontaneous speech, token test, repetition, written language, confrontation
      naming, comprehension). In the multivariate regression analysis, comprehension
      was the only function of the language to be predictor of the final total-FIM
      (beta = +0.35) and final cognitive-FIM (beta = +0.61). Comprehension was a
      predictor of total-FIM (beta = +0.27) and cognitive-FIM (beta = +0.54) as well,
      when additional backward stepwise regression analysis (which did not include
      comprehension and expression scores in the final total- and cognitive-FIM) was
      performed. When multivariate regression analysis took into consideration only
      language functions as independent variables, spontaneous speech (beta = +0.41)
      only was the predictor of motor-FIM. The study highlights that AAT is the
      predictor of functional outcome in the patient with aphasia. Among the functions
      of language, comprehension seems to be the most important predictive factor of
      total- and cognitive-FIM, while spontaneous speech seems to be a predictor of
      motor-FIM.

PMID- 21181542
TI  - Postprandial ghrelin response is reduced in patients with Parkinson's disease and
      idiopathic REM sleep behaviour disorder: a peripheral biomarker for early
      Parkinson's disease?
AB  - Ghrelin, an orexigenic peptide, has multiple functions, which include promoting
      gastrointestinal motility and influencing higher brain functions. Experimental
      data suggest that ghrelin has neuroprotective potential in the MPTP mouse model
      of Parkinson's disease (PD). PD patients show delayed gastric emptying and other
      symptoms that may relate to disturbed excretion of ghrelin. No data are available
      on postprandial ghrelin response in patients with PD and idiopathic REM sleep
      behaviour disorder (iRBD)--a condition considered a putative preclinical stage of
      PD. We measured fasting and postprandial ghrelin serum concentrations in 20
      healthy controls, 39 (including 19 drug-naive) PD patients and 11 iRBD patients
      using a commercial radioimmunoassay for total ghrelin. For statistical analysis
      we employed ANCOVA and post-hoc testing with Bonferroni's method. Controls showed
      a decrease of mean fasting ghrelin serum concentrations in the early postprandial
      phase, followed by a recuperation starting 60 min after the test meal and
      reaching a maximum at 300 min. This recuperation was less pronounced in PD and
      iRBD; the slope of relative postprandial ghrelin recovery was different between
      the investigated groups (p = 0.007). Post-hoc testing showed a difference between
      controls and PD patients (p = 0.002) and between controls and iRBD patients (p =
      0.037). The dynamic regulation of ghrelin in response to food intake is partially
      impaired in subjects at putative preclinical (iRBD) and clinical stages of PD.
      Reduced ghrelin excretion might increase the vulnerability of nigrostriatal
      dopaminergic neurons as suggested by animal studies. The impaired ghrelin
      excretion might qualify as a peripheral biomarker and be of diagnostic or
      therapeutic value.

PMID- 21181543
TI  - Low-grade CSF leaks in endoscopic trans-sphenoidal pituitary surgery: efficacy of
      a simple and fully synthetic repair with a hydrogel sealant.
AB  - BACKGROUND: Intra-operative CSF leak during endoscopic trans-sphenoidal surgery
      is not uncommon. Surgical repair with a variety of autologous grafts, rigid
      buttresses and CSF diversion techniques that add time and complexity have been
      reported. OBJECTIVE: To describe a simple and purely synthetic closure for low
      grade CSF leaks following endoscopic trans-sphenoidal pituitary surgery. METHODS:
      A retrospective review of all endoscopic trans-sphenoidal surgery undertaken for
      pituitary pathology between 2005 and 2010 was carried out. The grade of CSF leak
      and success of graded repair was noted. Patients with no CSF leak (grade 0) had
      gelatin sponge placed in the tumour cavity. In those with low-grade CSF leak
      through small arachnoid defects (grade 1), repair was carried out using gelatin
      sponge and hydrogel sealant overlay. CSF diversion was not employed for low-grade
      CSF leaks. RESULTS: Of the 255 endoscopic trans-sphenoidal surgeries, 158 (62%)
      had no leak (grade 0) and 74 (29%) had a low-grade leak (grade 1). Repairs in all
      cases were of grade 0, and all but two cases of grade 1 CSF leak were successful
      at a mean follow-up of 29 months. The 2 (2.7%) post-operative CSF leaks were seen
      within 6 weeks of surgery. Both cases were related to bouts of sneezing and were
      repaired using further trans-sphenoidal surgery and/or lumbar CSF diversion.
      CONCLUSIONS: A simple purely synthetic repair of low-grade CSF leaks is
      described. This repair is safe and comparable in efficacy whilst avoiding the
      morbidity related to more complex sellar reconstructions previously described.

PMID- 21181544
TI  - Diphenyleneiodonium inhibits the activation of mitogen-activated protein kinases
      and the expression of monocyte chemoattractant protein-1 in Helicobacter pylori
      infected gastric epithelial AGS cells.
AB  - OBJECTIVE: To investigate whether NADPH oxidase induces MCP-1 expression and the
      activation of mitogen-activated protein kinases (MAPKs) in H. pylori-infected
      gastric epithelial cells. MATERIAL: H. pylori in Korean isolates, human gastric
      epithelial AGS cells TREATMENT: AGS cells pretreated with or without an NADPH
      oxidase inhibitor diphenyleneiodonium (DPI) are cultured in the presence of H.
      pylori at a bacterium/cell ratio of 300:1. METHODS: Reactive oxygen species (ROS)
      and MCP-1 were determined by confocal microscopy and enzyme-linked immonosorbent
      assay. NADPH oxidase activity was measured by lucigenin assay. mRNA expression of
      MCP-1 was analyzed by reverse transcription-polymerase chain reaction. Levels of
      MAPKs were assessed by Western blot analysis. RESULTS: H. pylori induced increase
      in ROS, NADPH oxidase activity, MCP-1 expression, and the activation of MAPKs
      including extracellular signal-regulated kinases, p38, and jun N-terminal kinases
      in AGS cells, which was inhibited by DPI. CONCLUSION: Inhibiting NADPH oxidase by
      DPI suppresses H. pylori-induced activation of MAPKs and MCP-1 expression in AGS
      cells.

PMID- 21181545
TI  - Magnetic resonance imaging and image analysis for assessment of HPMC matrix
      tablets structural evolution in USP Apparatus 4.
AB  - PURPOSE: The purpose of the study was to present a methodology for the processing
      of Magnetic Resonance Imaging (MRI) data for the quantification of the dosage
      form matrix evolution during drug dissolution. The results of the study were
      verified by comparison with other approaches presented in literature. METHODS: A
      commercially available, HPMC-based quetiapine fumarate tablet was studied with a
      4.7T MR system. Imaging was performed inside an MRI probe-head coupled with a
      flow-through cell for 12 h in circulating water. The images were segmented into
      three regions using threshold-based segmentation algorithms due to trimodal
      structure of the image intensity histograms. RESULTS: Temporal evolution of dry
      glassy, swollen glassy and gel regions was monitored. The characteristic features
      were observed: initial high expansion rate of the swollen glassy and gel layers
      due to initial water uptake, dry glassy core disappearance and maximum area of
      swollen glassy region at 4 h, and subsequent gel layer thickness increase at the
      expense of swollen glassy layer. CONCLUSIONS: The temporal evolution of an HPMC
      based tablet by means of noninvasive MRI integrated with USP Apparatus 4 was
      found to be consistent with both the theoretical model based on polymer
      disentanglement concentration and experimental VIS/FTIR studies.

PMID- 21181546
TI  - Disulfide-based poly(amido amine)s for siRNA delivery: effects of structure on
      siRNA complexation, cellular uptake, gene silencing and toxicity.
AB  - PURPOSE: RNA interference (RNAi) is a process by which small interfering RNAs
      (siRNA) induce sequence-specific gene silencing. Therefore, siRNA is an emerging
      promise as a novel therapeutic. In order to realize the high expectations for
      therapeutic applications, efficient delivery systems for siRNA are necessary.
      METHODS: In this study, a new series of biodegradable poly(amido amine)s with
      disulfide linkages in the backbone was synthesized out of N,N'
      cystaminebisacrylamide (CBA), 4-amino-1-butanol (ABOL) and ethylene diamine
      (EDA). Effects of different percentages of butanolic side chains and protonatable
      fragments in the main chain on siRNA complexation, cellular uptake, gene
      silencing and toxicity were investigated. RESULTS: Incorporation of EDA in the
      polymer resulted in increased siRNA condensation. Efficient siRNA condensation
      was shown to be necessary for cellular uptake; however, excess of polymer
      decreased siRNA uptake for polymers with high amounts of EDA. Silencing
      efficiency did not correlate with uptake, since silencing increased with
      increasing w/w ratio for all polymers. More than 80% knockdown was found for
      polyplexes formed with polymers containing 25% or 50% EDA, which was combined
      with low cytotoxicity. CONCLUSIONS: Poly(amido amine)s with minor fractions of
      protonatable fragments in the main chain are promising carriers for delivery of
      siRNA.

PMID- 21181547
TI  - Current and future drug targets in weight management.
AB  - Obesity will continue to be one of the leading causes of chronic disease unless
      the ongoing rise in the prevalence of this condition is reversed. Accumulating
      morbidity figures and a shortage of effective drugs have generated substantial
      research activity with several molecular targets being investigated. However,
      pharmacological modulation of body weight is extremely complex, since it is
      essentially a battle against one of the strongest human instincts and highly
      efficient mechanisms of energy uptake and storage. This review provides an
      overview of the different molecular strategies intended to lower body weight or
      adipose tissue mass. Weight-loss drugs in development include molecules intended
      to reduce the absorption of lipids from the GI tract, various ways to limit food
      intake, and compounds that increase energy expenditure or reduce adipose tissue
      size. A number of new preparations, including combinations of the existing drugs
      topiramate plus phentermine, bupropion plus naltrexone, and the selective 5
      HT(2C) agonist lorcaserin have recently been filed for approval. Behind these
      leading candidates are several other potentially promising compounds and
      combinations currently undergoing phase II and III testing. Some interesting
      targets further on the horizon are also discussed.

PMID- 21181548
TI  - The role of the transition metal copper and the ionophore A23187 in the
      development of Irinophore CTM.
AB  - PURPOSE: A liposomal irinotecan formulation referred to as Irinophore C relies on
      the ability of copper to complex irinotecan within the liposome. It is currently
      being evaluated for critical drug-loading parameters. Studies presented here were
      designed to determine the optimum copper concentration required for the effective
      encapsulation and retention of irinotecan into liposomes. METHODS:
      Distearoylphosphatidylcholine/cholesterol liposomes were formulated using buffers
      containing various copper or manganese concentrations, and irinotecan loading was
      determined in the presence and absence of divalent metal ionophore A23187. The
      rate and extent of irinotecan encapsulation and the rate of irinotecan release
      from the liposomes were assessed. The amount of copper retained inside liposomes
      following irinotecan loading and the effect of copper on membrane permeability
      were determined. RESULTS: Efficient (>98%) irinotecan loading was achieved using
      encapsulated copper concentrations of 50 mM. However, irinotecan release was
      copper concentration dependent, with a minimum 300 mM concentration required for
      optimal drug retention. The presence of copper increased liposomal membrane
      permeability. CONCLUSION: Results explain why irinotecan loading rates are
      enhanced in the presence of formulations prepared with copper, and we speculate
      that the Irinophore C formulation exhibits improved drug retention, due to
      generation of a complex between copper and irinotecan.

PMID- 21181550
TI  - Iontophoresis-facilitated delivery of prednisolone through throat skin to the
      trachea after topical application of its succinate salt.
AB  - PURPOSE: The possibility of direct delivery of steroids through the skin to the
      trachea and the effect of iontophoresis on delivery efficacy were evaluated after
      the application of an ionic steroidal prodrug, prednisolone sodium succinate (PS
      Na), to the throat skin. METHODS: Fluorescein sodium salt (FL-Na) and PS-Na were
      applied as model compounds at a concentration of 1% in pH 7.4 phosphate-buffered
      saline to the throat skin of hairless rats, and constant current-cathodal
      iontophoresis (0.4 mA/cm(2)) was performed for 8 or 10 h. RESULTS: In vitro
      permeation experiment involving cathodal iontophoresis through excised hairless
      rat abdominal skin revealed 30- and 10-times higher levels of skin permeation of
      PS and its active drug, prednisolone (P), than those induced without
      iontophoresis. In vivo iontophoresis treatment of the rat's throat skin produced
      2.6-, 1.6- and 12-times higher FL, PS and P concentrations, respectively, in the
      trachea than those observed without iontophoresis. CONCLUSION: The present
      results suggest the usefulness of topical application of the ionic steroidal
      prodrugs onto throat skin followed by iontophoresis treatment for directly
      delivering the steroid to the trachea.

PMID- 21181551
TI  - Investigating the effect of polymeric approaches on circulation time and physical
      properties of nanobubbles.
AB  - PURPOSE: A challenge in the field of nanobubbles, including lipobubbles and
      polymeric nanobubbles, is identification of formulation approaches to enhance
      circulation time or "bubble life" in the specific organ to allow for organ
      visualization. The aim of this study was to investigate the potential of two
      specific preparation approaches, polymeric surface modification to lipobubbles
      and a one-step approach for the preparation of ionotropically originated
      polymeric hydrogel nanobubbles for the production of biocompatible,
      biodegradable, and sufficiently echogenic ('flexible') bubbles, preferably within
      the nanometer range, that possess an enhanced in vivo lifetime compared to an
      unmodified lipobubble to allow visualization of the lymph node vasculature.
      METHODS: In the first approach, formed liposomes (basic and polymerically
      enhanced) were sequentially layered with appropriate cationic and anionic
      polyelectrolytes followed by transformation into polymer-coated nanobubbles. In
      addition, a one-step approach was employed for the fabrication of ionotropically
      originated polymeric hydrogel bubbles. RESULTS: Bubble lifetime was marginally
      enhanced by self-deposition of polyelectrolytes onto the normal lipobubble,
      however, not significantly (P = 0.0634). In general, formulations possessing a
      higher ratio of anionic:cationic coats and highly anionic overall surface charge
      (-20.62 mV to -17.54 mV) possessed an enhanced lifetime. The improvement in
      bubble lifetime was significant when a purely polymeric polyionic hydrogel bubble
      shell was instituted compared to a normal unmodified lipobubble (P = 0.004).
      There was enhanced persistence of these systems compared to lipobubbles,
      attributed to the highly flexible, interconnected hydrogel shell which minimized
      gas leakage. The prolonged contrast signal may also be attributed to a degree of
      polymeric deposition/endothelial attachment. CONCLUSIONS: This study identified
      the relevance of polymeric modifications to nanobubbles for an improved
      circulating lifetime, which would be essential for application of these systems
      in passive drug or gene targeting via the enhanced permeability and retention
      effect.

PMID- 21181549
TI  - Designing dendrimers for drug delivery and imaging: pharmacokinetic
      considerations.
AB  - Dendrimers have well-organized high branches with a layered architecture
      providing a series of versatile chemical modification for various purposes.
      Consequently, this dendrimer nanotechnology explores a new promising class of
      nanoscale carriers for therapeutic drugs and imaging reagents using passive and
      active targeting approaches. By controlling dendritic structures, the biological
      fate of dendrimer/dendrimer-based drugs can be significantly altered based on
      their intrinsic physicochemical properties, including the hydrophilicity of the
      unit molecules, particle size, surface charge, and modification. Accordingly,
      pharmacokinetic aspects play an important role in the design and development of
      dendrimer systems for successful in vivo application and clinical translation.
      This review focuses on the recent progress regarding dendritic architectures,
      structure-related toxicity, and critical factors affecting the pharmacokinetics
      and biodistribution of dendrimer/dendrimer-based drugs. A better understanding of
      the basic aspects of dendritic systems and their pharmacokinetics will help to
      develop a rationale for the design of dendrimers for the controlled delivery of
      drugs and imaging reagents for therapeutic or diagnostic purposes.

PMID- 21181552
TI  - Channels of change: contrasting network mechanisms in the use of interventions.
AB  - This study informs community science, and seeks to narrow the research-to
      practice gap, by examining how the interpersonal networks within a setting
      influence individuals' use of interventions. More specifically, it explores the
      role of two network mechanisms-cohesion and structural similarity-in urban
      elementary school teachers' use of interventions designed to improve academic and
      behavioral outcomes for students. Lagged regression models examine how position
      in advice giving networks influenced weekly use of the daily report card and peer
      assisted learning by kindergarten through fourth grade teachers in three schools.
      Results indicate that intervention use spreads among teachers with similar
      patterns of advice-giving relationships (i.e., via structural similarity), rather
      than from teachers who are sources of advice (i.e., via cohesion). These results
      are consistent with findings in other settings, and suggest that researchers
      wishing to increase the use of an intervention should select change agents based
      on their patterns of their relationships, rather than on their direct
      connections.

PMID- 21181553
TI  - Disconnections of African American public housing residents: connections to
      physical activity, dietary habits and obesity.
AB  - African American (AA) and low SES populations report poor health behaviors and
      outcomes. This study aimed to increase understanding of barriers to participating
      in healthful behaviors and programs in AA residents of public housing. Twenty two
      apparently healthy, AA residents (50% female, M = 43.9 years) completed in depth
      interviews, which were taped, transcribed and analyzed using a constant
      comparison approach. Residents demonstrated some awareness of health
      recommendations, but described limited adherence. Physical activity for
      recreation was reported as primarily for youth, with adults engaging in limited
      physical activity (primarily incidental to other activities). Barriers reported
      by residents were both personal and environmental. Few residents were aware of
      local neighborhood opportunities for physical activity or healthful eating.
      Future efforts should focus on increasing understanding of health promoting
      behaviors and awareness and efficacy of residents to connect with the resources
      of their surrounding communities.

PMID- 21181555
TI  - Religious congregations as mediating structures for social justice: a multilevel
      examination.
AB  - Scholars in the field of community psychology have called for a closer
      examination of the mediating role that religious congregations serve in society,
      especially in relation to the promotion of social justice. The current study
      provides such an examination, offering a multilevel examination of religious
      individuals (n = 5,123) nested within religious congregations (n = 62) with a
      particular focus on how individual and congregational level variables (i.e.
      theological orientation, frequency of religious attendance, bonding and bridging
      social capital) predict individual prioritization of and participation in
      congregational social justice activities. Findings indicated that individual
      level theological orientation was associated with prioritization, and
      demographics and social capital bonding were associated with prioritization and
      participation. Furthermore, congregational bridging social capital was associated
      with the prioritization of justice, whereas congregational theological
      orientation moderated the associations between frequency of religious
      participation for both prioritization of and participation in congregational
      justice activities. These findings show that specific aspects of the
      congregational setting (i.e., congregational theological orientation) are
      important to the individual prioritization of and participation in social justice
      activities. These findings provide support for the role of religious
      congregations as mediating structures for social justice. Implications for future
      research are also discussed.

PMID- 21181556
TI  - Do social connections and hope matter in predicting early adolescent violence?
AB  - We tested relationships between social connections, hope, and violence among
      young adolescents from socially distressed urban neighborhoods, and examined
      whether relationships between adolescents' family and school connectedness and
      violence involvement were mediated by hopefulness. Data were from middle school
      students involved in the Lead Peace demonstration study. The sample (N = 164) was
      51.8% female; 42% African American, 28% Asian, 13% Hispanic, and 17% mixed race
      or other race; average age was 12.1 years; 46% reported physical fighting in the
      past year. In multivariate models, parent-family connectedness was protective
      against violence; school connectedness was marginally protective. Hopefulness was
      related to lower levels of violence. The relationship between school
      connectedness and violence was mediated by hopefulness; some evidence for
      mediation also existed in the family-parent connectedness and violence
      relationship. Findings warrant continued exploration of hopefulness as an
      important protective factor against violence involvement, and as a mediator in
      relationships between social connections and violence involvement.

PMID- 21181557
TI  - The three-dimensional structure of the FMO protein from Pelodictyon phaeum and
      the implications for energy transfer.
AB  - The Fenna-Matthews-Olson (FMO) antenna protein from the green bacterium
      Pelodictyon phaeum mediates the transfer of energy from the peripheral chlorosome
      antenna complex to the membrane-bound reaction center. The three-dimensional
      structure of this protein has been solved using protein crystallography to a
      resolution limit of 2.0 A, with R(work) and R(free) values of 16.6 and 19.9%,
      respectively. The structure is a trimer of three identical subunits related by a
      threefold symmetry axis. Each subunit has two beta sheets that surround 8
      bacteriochlorophylls. The bacteriochlorophylls are all five-coordinated, with the
      axial ligand being a histidine, serine, backbone carbonyl, or bound water
      molecule. The arrangement of the bacteriochlorophylls is generally well conserved
      in comparison to other FMO structures, but differences are apparent in the
      interactions with the surrounding protein. In this structure the position and
      orientation of the eighth bacteriochlorophyll is well defined and shows
      differences in its location and the coordination of the central Mg compared to
      previous models. The implications of this structure on the ability of the FMO
      protein to perform energy transfer are discussed in terms of the experimental
      optical measurements.

PMID- 21181559
TI  - Normoxically overexpressed hypoxia inducible factor 1-alpha is involved in
      arsenic trioxide resistance acquisition in hepatocellular carcinoma.
AB  - BACKGROUND: The aim of this study was to examine the underlying signaling
      mechanisms of arsenic trioxide (ATO)-mediated anticancer effects and the
      responsible biomarker(s) for the acquired resistance in human heptatocellular
      carcinoma (HCC). MATERIALS AND METHODS: The therapeutic effects of ATO were
      examined using 2 characteristically distinct HCC cell lines, Hep-J5
      (overexpressing HIF-1alpha/GRP78) and SK-Hep-1 (the matched control). ATO
      mediated proliferation inhibition, oxidative stress, and apoptosis were analyzed
      using flowcytometric analysis and western blotting. The role of HIF-1alpha and
      GRP78 in HCC resistance to ATO treatment was determined using RNA silencing and
      inhibitor approaches. RESULTS: SK-Hep-1 cells, lacking both HIF-1alpha and GRP78
      expressions were responsive to ATO-induced apoptosis via an oxidative-nitrosative
      mechanism. Intracellular glutathione depletion and lipid peroxidation have been
      identified as the early cascade of events preceding apoptosis via cytochrome c
      release and the severe drop of mitochondrial membrane potential (MMP).
      Conversely, Hep-J5 cells, with normoxic coexpression of HIF-1alpha and GRP78,
      were resistant to ATO-induced apoptosis. GRP78-silenced Hep-J5 cells remained
      resistant to ATO treatment. In contrast, ATO resistance in Hep-J5 cells was
      overcome by the addition of YC-1, a HIF-1alpha inhibitor. CONCLUSIONS: HIF-1alpha
      was identified as the major positive modifier for ATO resistance acquisition in
      HCC, and it represents a prime molecular target for overcoming ATO resistance.

PMID- 21181560
TI  - A video-intervention to improve clinician attitudes toward patients with sickle
      cell disease: the results of a randomized experiment.
AB  - BACKGROUND: Clinician attitudes toward patients are associated with variability
      in the quality of health care. Attitudes are typically considered difficult to
      change, and few interventions have attempted to do so. Negative attitudes toward
      adults with sickle cell disease have been identified as an important barrier to
      the receipt of appropriate pain management for this patient population.
      OBJECTIVE: To test the effect of a video-intervention designed to improve
      clinician attitudes toward adults with sickle cell disease. INTERVENTIONS: An 8
      minute video depicting a clinician expert and patients discussing challenges in
      seeking treatment for sickle cell pain. DESIGN AND PARTICIPANTS: A randomized
      post-test only control group design was used to assess the impact of the
      intervention on the attitudes of 276 nurses and housestaff working at a large,
      urban, academic medical center. MAIN MEASURES: Attitudes toward adult sickle cell
      patients assessed using 5- and 6-point Likert-scale items. Exploratory factor
      analysis was used to identify underlying attitudinal domains and develop scales.
      Examples of the negative and positive attitudes assessed include clinician
      estimates of the percentage of SCD patients that exaggerate pain (negative) or
      make clinicians glad they went into medicine (positive). KEY RESULTS: Compared to
      the control group, the intervention group exhibited decreased negative attitudes
      (Difference in means = -8.9, 95%CI [-14.2, -3.6]; Cohen's d = 0.41), decreased
      endorsement of certain patient behaviors as "concern-raising" (Difference in
      means = -7.8, 95%CI [-13.1, -2.5]; Cohen's d = 0.36), and increased positive
      attitudes toward sickle cell patients (Difference in means = 6.6, 95% CI [0.6,
      12.6]; Cohen's d = 0.27). CONCLUSIONS: Our results suggest that the attitudes of
      clinicians toward sickle cell patients may be improved through a short and
      relatively easy to implement intervention. Whether the attitudinal differences
      associated with our intervention are sustainable or are linked to clinical
      outcomes remains to be seen.

PMID- 21181561
TI  - Computed tomography reflected endocrine function of the pancreas.
AB  - BACKGROUNS/AIMS: There are few studies about the assessment of pancreatic
      function using computed tomography (CT) volumetry. In this study, we examined the
      correlation between CT volumetry and endocrine parameters (blood glucose and
      HbA1c) of the pancreas. METHODS: A total of 68 patients underwent enhanced CT for
      pancreatic disease from January to December in 2008. In particular, we analyzed
      the correlation of diabetic status and pancreatic CT parameters at 1 year after
      pancreatoduodenectomy in 32 patients. CT parameters including volume, volume/body
      weight, arterial phase density, the arterial phase to portal phase density ratio
      (A/P ratio) of the pancreas, and size of pancreatic duct were also analyzed.
      Correlation between CT parameters and diabetic status was analyzed preoperatively
      and postoperatively by ANOVA test. RESULTS: The preoperative diabetic status and
      parameters correlated well with arterial phase density (p = 0.004), A/P ratio,
      and pancreatic duct size (p < 0.0001). In the patients who underwent
      pancreatectomy, two out of 25 patients without preoperative diabetes mellitus
      (DM) had DM, and two out of seven patients with preoperative DM recovered from
      DM. Postoperative CT parameters correlated with the DM status 1 year after
      pancreatectomy. CONCLUSION: CT is a useful modality for evaluation of the
      pancreatic endocrine function and could be used for the prediction of
      postoperative diabetic outcome.

PMID- 21181562
TI  - gamma knife stereotactic radiosurgery in the management of cluster headache.
AB  - Gamma knife stereotactic radiosurgery (SRS) has proven to be an effective
      management approach for trigeminal neuralgia and as a minimally invasive
      alternative management option for cluster headache (CH). In CH, patients undergo
      single-session focused irradiation of the trigeminal nerve root (TN), sometimes
      coupled with irradiation of the sphenopalatine ganglion (SPG) as well. SRS
      provides early pain relief in most patients, but is associated with trigeminal
      sensory dysfunction in some patients. In the future, a prospective trial that
      compares a single target of TN to dual targets of both the TN and SPG may provide
      further understanding of the value of SRS for CH.

PMID- 21181563
TI  - Poisson probability function can help optimize trauma operating room
      availability.

PMID- 21181564
TI  - If we have bandwagons, magic bullets, and theoretical constructs, why do we need
      randomized clinical trials in transfusion medicine and perioperative hemostasis?

PMID- 21181565
TI  - Case report: transesophageal echocardiography detected severe regional wall
      motion abnormalities signifying failed reimplantation of an anomalous left main
      coronary artery.
AB  - PURPOSE: Anomalous coronary arteries comprise a spectrum ranging from benign to
      fatal. The most ominous lesion that occurs is the left main coronary artery
      (LMCA) originating from the opposite aortic sinus. This defect usually presents
      as sudden death in a healthy young adult immediately after exercise. We report a
      case of reimplantation of an anomalous LMCA, discovered in a 15-yr-old girl
      during investigations for atypical chest pain. CLINICAL FEATURES: The
      intraoperative transesophageal echocardiography (TEE) confirmed that the
      anomalous LMCA originated from the right aortic sinus. The anomalous LMCA was
      reimplanted to the left aortic sinus, but the patient could not be weaned from
      cardiopulmonary bypass because of severe hypotension. The TEE demonstrated severe
      regional wall motion abnormalities (RWMA) in the territory of the LMCA with
      akinesis of the septal, antero-septal, anterior, and lateral walls. Using TEE,
      flow could not be seen in the reimplanted LMCA, hence, the differential diagnosis
      was established as failed reimplantation of the LMCA, coronary air embolism, or
      poor myocardial preservation, but the latter two causes were extremely unlikely.
      Surgical inspection of the reimplanted LMCA did not reveal a correctable problem.
      A left internal mammary artery to proximal left anterior descending (LAD) artery
      graft was completed with resolution of the previous RWMA. Recovery of function in
      the lateral wall confirmed retrograde flow from the LAD into the circumflex
      artery. CONCLUSIONS: Transesophageal echocardiography was critical in rapidly
      determining the cause of hemodynamic instability following this uncommon
      operation. Despite the availability of newer techniques to detect and quantify
      RWMA, the assessment of wall motion and contractility remains subjective.

PMID- 21181566
TI  - Inhibition of learning and memory by general anesthetics.
AB  - PURPOSE: Today's general anesthetics were developed empirically according to
      their ability to produce memory blockade, analgesia, immobility, and
      unconsciousness. Thus, a major outstanding question remains: How do anesthetics
      produce their desirable behavioural end points at the molecular level?
      Understanding the mechanisms underlying memory blockade is of particular
      importance, because some patients experience the unexpected recall of events
      during anesthesia while others experience persistent memory deficits in the
      postoperative period. This review provides a brief summary of the acute memory
      blocking properties of general anesthetics and the neuronal substrates that most
      likely contribute to memory loss. PRINCIPAL FINDINGS: Studies in human volunteers
      and laboratory animals have shown that the memory-blocking properties of general
      anesthetics depend on the specific drug, the dose, the type of memory, and the
      experimental paradigm, as well as the species and age of the experimental
      subject. The cellular substrates of memory blockade include an increase in
      neuronal inhibition by gamma-aminobutyric acid subtype A receptors, a decrease in
      excitatory glutamatergic neurotransmission, and alterations in synaptic
      plasticity. CONCLUSIONS: Anesthetics target different receptors and brain regions
      to modify the various forms of memory. In the hippocampus, extrasynaptic gamma
      aminobutyric acid subtype A receptors may play a particularly important role.
      Knowledge regarding the molecular basis of memory blockade may help to address
      memory disorders associated with the anesthetic state.

PMID- 21181567
TI  - Functional multidisciplinary rehabilitation versus outpatient physiotherapy for
      non specific low back pain: randomized controlled trial.
AB  - INTRODUCTION: In recent decades the treatment of non-specific low back pain has
      turned to active modalities, some of which were based on cognitive-behavioural
      principles. Non-randomised studies clearly favour functional multidisciplinary
      rehabilitation over outpatient physiotherapy. However, systematic reviews and
      meta-analysis provide contradictory evidence regarding the effects on return to
      work and functional status. The aim of the present randomised study was to
      compare long-term functional and work status after 3-week functional
      multidisciplinary rehabilitation or 18 supervised outpatient physiotherapy
      sessions. METHODS: 109 patients with non-specific low back pain were randomised
      to either a 3-week functional multidisciplinary rehabilitation programme,
      including physical and ergonomic training, psychological pain management, back
      school and information, or 18 sessions of active outpatient physiotherapy over 9
      weeks. Primary outcomes were functional disability (Oswestry) and work status.
      Secondary outcomes were lifting capacity (Spinal Function Sort and PILE test),
      lumbar range-of-motion (modified-modified Schober and fingertip-to-floor tests),
      trunk muscle endurance (Shirado and Biering-Sorensen tests) and aerobic capacity
      (modified Bruce test). RESULTS: Oswestry disability index was improved to a
      significantly greater extent after functional multidisciplinary rehabilitation
      compared to outpatient physiotherapy at follow-up of 9 weeks (P = 0.012), 9
      months (P = 0.023) and 12 months (P = 0.011). Work status was significantly
      improved after functional multidisciplinary rehabilitation only (P = 0.012),
      resulting in a significant difference compared to outpatient physiotherapy at 12
      months' follow-up (P = 0.012). Secondary outcome results were more contrasted.
      CONCLUSIONS: Functional multidisciplinary rehabilitation was better than
      outpatient physiotherapy in improving functional and work status. From an
      economic point of view, these results should be backed up by a cost-effectiveness
      study.

PMID- 21181568
TI  - Limitations of infrared ear temperature measurement in clinical practice.
AB  - PRINCIPLES: Detection of elevated body temperature is critical in the early
      diagnosis of sepsis. Due to its convenience, infrared ear temperature measurement
      (IETM) has become the standard of care. Unfortunately, the limitations of this
      method are largely unexplored. OBJECTIVE: To evaluate potential limitations of
      IETM, including the presence of cerumen on otoscopy, depth of penetration, side
      of measurement, and the impact of acclimatisation to room temperature. METHODS:
      In this prospective cohort study, 333 patients presenting to the medical
      emergency department underwent serial IETM before and after otoscopy and cleaning
      of the external auditory canal. The primary endpoint was defined as mean change
      in infrared ear temperature (IET) before and after removal of cerumen. We also
      tested for the effect of penetration depth, side of measurement and impact of
      acclimatisation. RESULTS: Otoscopy revealed cerumen in 98 patients (29%). Cerumen
      had a weak but statistically significant impact on IETM. The removal of cerumen
      obturans resulted in a rise in IET of 0.20  degrees C (95% CI 0.10-0.28  degrees
      C, P = 0.03). The effects of penetration depth (P = 0.39), side of measurement (P
      = 0.78) and impact of acclimatisation (P = 0.82) were not significant.
      CONCLUSIONS: Cerumen has a statistically significant, albeit not clinically
      meaningful, influence on IETM. Thus routine ear inspection prior to the use of
      IETM is not warranted. IETM provides highly reproducible assessments of IET
      irrespective of penetration depth, side of measurement and acclimatisation.

PMID- 21181569
TI  - Maternal smoking during pregnancy and fetal growth. Effects in preterm infants of
      gestational age less than 33 weeks.
AB  - OBJECTIVE: To evaluate the effects of maternal smoking during pregnancy on foetal
      growth in preterm infants with gestational age (GA) <33 weeks. POPULATION AND
      METHODS: Prospective observational cross-sectional study from two French
      perinatal networks cohort of preterm infants. Cases were 358 very preterm infants
      (GA 24-32 weeks) divided into two groups as maternal smokers (129) and non
      smokers (229). 361 term infants (GA 37-41 weeks) also divided into two groups as
      maternal smokers (129) and non-smokers (232) served as comparison group
      (controls). We studied the influence of maternal smoking on foetal anthropometric
      growth parameters (BW, BL and head circumference defined according to AUDIPOG
      curves) in groups and compared cases and controls. Other causes of foetal growth
      restriction were excluded. RESULTS: Maternal characteristics (age, height, pre
      pregnancy body weight, parity, foetus sex) were similar in both groups and sub
      groups. Mothers who smoked were younger (P <0.001), more likely to be unemployed
      (P <0.001) and to have undergone less school education (P <0.001). Smoking did
      not alter foetal growth in preterm infants: maternal smokers versus non-smokers
      BW (P = 0.52), BL (P = 0.44) and HC (P = 0.81). Growth restriction was marked in
      term infants with BW (P <0.001), BL (P <0.001) and HC (P <0.01). In multivariate
      analysis, after adjustment for other confounding factors, foetal growth appeared
      to be significantly altered by maternal smoking during pregnancy only in term
      infants. CONCLUSION: Our study suggests that effects of maternal smoking during
      pregnancy on foetal growth are gestational age-dependent.

PMID- 21181570
TI  - Evaluation of the antifouling properties of 3-alyklpyridine compounds.
AB  - One of the most promising alternative technologies to antifouling (AF) biocides
      based on toxic heavy metals lies in the development of natural eco-friendly
      biocides. The present study evaluates the AF potential of structurally different
      compounds containing a 3-alkylpyridine moiety. The products, namely poly 3
      alkylpyridinium salts, saraine, and haminols, were either extracted or derived
      from natural sources (the sponges Haliclona sp. and Reniera sarai and the mollusc
      Haminoea fusari), or obtained by chemical synthesis. All the molecules tested
      showed generally good anti-settlement activity against larvae of the barnacle
      Amphibalanus (=Balanus) amphitrite (EC(50) values between 0.19 and 3.61 MUg ml(
      1) and low toxicity (LC(50) values ranging from 2.04 to over 100 MUg ml(-1)) with
      non-target organisms. For the first time, the AF potential of a synthetic
      monomeric 3-alkylpyridine was demonstrated, suggesting that chemical synthesis is
      as a realistic way to produce large amounts of these compounds for future
      research and development of environmentally-friendly AF biocides.

PMID- 21181571
TI  - Biofilm retention on surfaces with variable roughness and hydrophobicity.
AB  - Biofilms on food processing equipment cause food spoilage and pose a hazard to
      consumers. The bacterial community on steel surfaces in a butcher's shop was
      characterized, and bacteria representative of this community enriched from minced
      pork were used to study biofilm retention. Stainless steel (SS) was compared to
      two novel nanostructured sol-gel coatings with differing hydrophobicity. Surfaces
      were characterized with respect to roughness, hydrophobicity, protein adsorption,
      biofilm retention, and community composition of the retained bacteria. Fewer
      bacteria were retained on the sol-gel coated surfaces compared to the rougher SS.
      However, the two sol-gel coatings did not differ in either protein adsorption,
      biofilm retention, or microbial community composition. When polished to a
      roughness similar to sol-gel, the SS was colonized by the same amount of bacteria
      as the sol-gel, but the bacterial community contained fewer Pseudomonas cells. In
      conclusion, biofilm retention was affected more by surface roughness than
      chemical composition under the condition described in this study.

PMID- 21181572
TI  - Automatic system for 3D reconstruction of the chick eye based on digital
      photographs.
AB  - The geometry of anatomical specimens is very complex and accurate 3D
      reconstruction is important for morphological studies, finite element analysis
      (FEA) and rapid prototyping. Although magnetic resonance imaging, computed
      tomography and laser scanners can be used for reconstructing biological
      structures, the cost of the equipment is fairly high and specialised technicians
      are required to operate the equipment, making such approaches limiting in terms
      of accessibility. In this paper, a novel automatic system for 3D surface
      reconstruction of the chick eye from digital photographs of a serially sectioned
      specimen is presented as a potential cost-effective and practical alternative.
      The system is designed to allow for automatic detection of the external surface
      of the chick eye. Automatic alignment of the photographs is performed using a
      combination of coloured markers and an algorithm based on complex phase order
      likelihood that is robust to noise and illumination variations. Automatic
      segmentation of the external boundaries of the eye from the aligned photographs
      is performed using a novel level-set segmentation approach based on a complex
      phase order energy functional. The extracted boundaries are sampled to construct
      a 3D point cloud, and a combination of Delaunay triangulation and subdivision
      surfaces is employed to construct the final triangular mesh. Experimental results
      using digital photographs of the chick eye show that the proposed system is
      capable of producing accurate 3D reconstructions of the external surface of the
      eye. The 3D model geometry is similar to a real chick eye and could be used for
      morphological studies and FEA.

PMID- 21181573
TI  - Cellular-scale transport in deformed skeletal muscle following spinal cord
      injury.
AB  - Deep tissue injury (DTI) is a severe pressure ulcer initiating in weight-bearing
      skeletal muscles. Being common in spinal cord injury (SCI) patients, DTI is
      associated with mechanical cell damage and ischaemia. Muscle microanatomy in SCI
      patients is characterised by reduced myofibre sizes and smaller, fewer
      capillaries. We hypothesise that these changes influence mass transport in SCI
      muscles, making DTI more probable. Using multiphysics models of microscopic cross
      sections through normal and SCI muscles, we studied effects of the following
      factors on transport of glucose and myoglobin (potential biomarker for early DTI
      detection): (i) abnormal SCI muscle microanatomy, (ii) large tissue deformations
      and (iii) ischaemia. We found that the build-up of concentrations of glucose and
      myoglobin is slower for SCI muscles, which could be explained by the pathological
      SCI microanatomy. These findings overall suggest that microanatomical changes in
      muscles post-SCI play an important role in the vulnerability of the SCI patients
      to DTI.

PMID- 21181574
TI  - Identification of capillary blood pressure levels at which capillary collapse is
      likely in a tissue subjected to large compressive and shear deformations.
AB  - Pressure ulcers (PU) are localised damage to skin and underlying tissues, caused
      by sustained tissue deformations and ischaemia. PU typically appear in
      insensitive or immobile patients, e.g. those with spinal cord injury (SCI) or
      geriatric patients. As these patients often experience fluctuations in blood
      pressure, and are also exposed to high-shear loads in their weight-bearing soft
      tissues during wheelchair sitting or bed rest, we used an inverse finite element
      method to determine the effects of capillary blood pressure (CBP) and shear
      deformations on occurrence of mechanical collapse in capillaries. We studied
      collapse in straight, U-shaped and bifurcated capillaries. All model
      configurations were consistent in demonstrating that the level of CBP has a
      considerable influence on the likelihood of capillary collapse in the
      physiological CBP range, particularly if shear is present. Our modelling
      therefore suggests that low CBP is a 'suspect' risk factor for PU in SCI and
      geriatric patients.

PMID- 21181575
TI  - Special issue: Eating disorders and mindfulness. Introduction.

PMID- 21181576
TI  - A mindful eating group as an adjunct to individual treatment for eating
      disorders: a pilot study.
AB  - The objective of this study was to investigate potential benefits of a Mindful
      Eating Group as an adjunct to long-term treatment for a variety of eating
      disorders. Individuals (N = 33) attending treatment at an outpatient treatment
      facility participated in the 10-week intervention designed to enhance awareness
      around hunger and satiety cues. Disordered eating symptoms were assessed pre- and
      post-intervention using the EAT-26. Significant reductions were found on all
      subscales of the EAT-26 with large effect sizes. No significant differences were
      identified between eating disorder diagnoses. Results suggest potential benefits
      of an adjunct mindfulness group intervention when treating a variety of eating
      disorders. Limitations are discussed.

PMID- 21181577
TI  - Mindfulness-Action Based Cognitive Behavioral Therapy for concurrent Binge Eating
      Disorder and Substance Use Disorders.
AB  - Individuals with Binge Eating Disorder (BED) often evidence comorbid Substance
      Use Disorders (SUD), resulting in poor outcome. This study is the first to
      examine treatment outcome for this concurrent disordered population. In this
      pilot study, 38 individuals diagnosed with BED and SUD participated in a 16-week
      group Mindfulness-Action Based Cognitive Behavioral Therapy (MACBT). Participants
      significantly improved on measures of objective binge eating episodes; disordered
      eating attitudes; alcohol and drug addiction severity; and depression. Taken
      together, MACBT appears to hold promise in treating individuals with co-existing
      BED-SUD.

PMID- 21181578
TI  - The application of mindfulness to eating disorders treatment: a systematic
      review.
AB  - The present study is an exploratory examination of the efficacy of the
      application of mindfulness-based interventions to the treatment of eating
      disorders. It employs a systematic review technique in which terms from the
      Psychological Index Terms of the American Psychological Association (APA) were
      chosen and analyzed in conjunction with Boolean operators. Using data obtained by
      the online consultation of references from 12 different bibliographical
      databases, 8 studies were included in the systematic review. Each study reported
      satisfactory results, although trial qualities were variable and sample sizes
      were small. Nonetheless, the current study found initial evidence supporting the
      effectiveness of mindfulness-based interventions to the treatment of eating
      disorders. The application of mindfulness-based interventions to the treatment of
      eating disorders remains a promising approach worthy of further research.

PMID- 21181579
TI  - Mindfulness-based eating awareness training for treating binge eating disorder:
      the conceptual foundation.
AB  - This paper reviews the conceptual foundation of mindfulness-based eating
      awareness training (MB-EAT). It provides an overview of key therapeutic
      components as well as a brief review of current research. MB-EAT is a group
      intervention that was developed for treatment of binge eating disorder (BED) and
      related issues. BED is marked by emotional, behavioral and physiological
      disregulation in relation to food intake and self-identity. MB-EAT involves
      training in mindfulness meditation and guided mindfulness practices that are
      designed to address the core issues of BED: controlling responses to varying
      emotional states; making conscious food choices; developing an awareness of
      hunger and satiety cues; and cultivating self-acceptance. Evidence to date
      supports the value of MB-EAT in decreasing binge episodes, improving one's sense
      of self-control with regard to eating, and diminishing depressive symptoms.

PMID- 21181580
TI  - Psychological inflexibility and symptom expression in anorexia nervosa.
AB  - The purpose of this article is to outline a model of anorexia nervosa (AN) as a
      disorder of psychological inflexibility, motivated by an insatiable desire for
      prediction and control with related intolerance for uncertainty. We describe
      preliminary data that provide initial support for this conceptualization and
      point to the ways in which mindfulness and acceptance-based strategies might be
      particularly useful for treating AN. This article is not intended to be an
      exhaustive literature review, rather a conceptual framework to guide future
      research and treatment development.

PMID- 21181581
TI  - Thinking through the body: the conceptualization of yoga as therapy for
      individuals with eating disorders.
AB  - Yoga has historically been viewed as a discipline that increases self-awareness
      through body based practices, meditation, self-study, and the reading of
      philosophical texts. In the 21st century the mindfulness techniques of yoga have
      been adapted as an adjunct to the treatment of individuals with eating disorders.
      In an effort to understand the conceptualization of yoga as therapy for
      individuals with eating disorders, this article juxtaposes how mindfulness based
      yoga is regarded in three disciplines: sociology, neuroscience, and the
      "spiritual texts" of yoga.

PMID- 21181582
TI  - Using mindful eating to treat food restriction: a case study.
AB  - This case study describes the application of the principles of mindful eating to
      the treatment of a case of anorexia nervosa. While many clinicians currently use
      mindful eating in their treatment of binge eating disorder and bulimia, it also
      may benefit clients who restrict. The client in this case study is a 19-year-old
      college student with a BMI of 17.9 and daily restriction of approximately 900
      1000 calories who exercises 1 hour daily. Over 15 sessions, she was introduced to
      the principle of mindful eating. There was an overall decline in restriction, her
      BMI raised to 19.5, and her caloric intake increased to approximately 1,500
      2,000.

PMID- 21181583
TI  - Integrating mindfulness into the therapy hour.

PMID- 21181584
TI  - 'The perfect is the enemy of the good' - ergonomics research and practice.
      Institute of Ergonomics and Human Factors Annual Lecture 2010.
AB  - The relationship between research and practice in ergonomics and human factors
      has rarely been addressed in the literature. This presents specific problems for
      researchers when seeking to relate their work to the research community. Equally,
      practitioners are often frustrated by the lack of appropriate research to meet
      their needs. This paper seeks to identify current drivers for ergonomics research
      along with an analysis of how these are changing. Specifically, the use of
      bibliometric data to assess research output and its impact on a multi
      disciplinary subject such as ergonomics is examined. Areas where action may be
      required to stimulate better research and improved practice are proposed. These
      include a greater role for the practitioner in completing the circle of knowledge
      and improving the evidence base for practice with, in particular, practitioners
      becoming more active in determining research priorities. It is concluded that
      combined effort is needed by researcher and practitioner communities to enable
      and promote a more effective understanding of the true impact of ergonomics
      across industry and society. STATEMENT OF RELEVANCE: The relationship between
      ergonomics research and practice is examined. Research 'drivers' are identified,
      including the influence of bibliometric data. Implications for researchers and
      practitioners are discussed. The role of practitioners in completing the circle
      of knowledge and improving the ergonomics evidence base is stressed, as is the
      need to promote the impact of ergonomics across society.

PMID- 21181585
TI  - Work environments for employee creativity.
AB  - Innovative organisations need creative employees who generate new ideas for
      product or process innovation. This paper presents a conceptual framework for the
      effect of personal, social-organisational and physical factors on employee
      creativity. Based on this framework, an instrument to analyse the extent to which
      the work environment enhances creativity is developed. This instrument was
      applied to a sample of 409 employees and support was found for the hypothesis
      that a creative work environment enhances creative performance. This paper
      illustrates how the instrument can be used in companies to select and implement
      improvements. STATEMENT OF RELEVANCE: The ergonomics discipline addresses the
      work environment mainly for improving health and safety and sometimes
      productivity and quality. This paper opens a new area for ergonomics: designing
      work environments for enhancing employee creativity in order to strengthen an
      organisation's capability for product and process innovation and, consequently,
      its competitiveness.

PMID- 21181586
TI  - The influence of 'Tall Man' lettering on errors of visual perception in the
      recognition of written drug names.
AB  - Visual errors in the perception of written drug names can reflect orthographic
      similarity amongst certain names. Drug names are typically printed in lowercase
      text. 'Tall Man' lettering, the capitalisation of the portions that differ
      amongst orthographically similar drug names, is employed in the field of
      medication labelling and prescribing to reduce medication errors by highlighting
      the area most likely to prevent confusion. The influence of textual format on
      visual drug name perception was tested amongst healthcare professionals (n = 133)
      using the Reicher-Wheeler task. Relative to lowercase text, Tall Man lettering
      improved accuracy in drug name perception. However, an equivalent improvement in
      accuracy was obtained using entirely uppercase text. Thus, character size may be
      a key determinant of perceptual accuracy for Tall Man lettering. Specific
      considerations for the manner in which Tall Man lettering might be best formatted
      and implemented in practice to reduce medication errors are discussed. STATEMENT
      OF RELEVANCE: Tall Man lettering aims to prevent medication errors by reducing
      visual confusions amongst orthographically similar drug names. It was found that,
      compared to lowercase text, Tall Man lettering improved accuracy in drug name
      perception. Character size appeared to be a key determinant of perceptual
      accuracy for Tall Man lettering.

PMID- 21181587
TI  - Type of visual feedback during practice influences the precision of the acquired
      internal model of a complex visuo-motor transformation.
AB  - This study investigated the influence of the type of visual feedback during
      practice with a complex visuo-motor transformation of a sliding two-sided lever
      on the acquisition of an internal model of the transformation. Three groups of
      participants, who practised with different types of visual feedback, were
      compared with regard to movement accuracy, curvature and movement time. One group
      had continuous visual feedback during practice and two groups were presented
      terminal visual feedback, either only the end position of the movement or the end
      position together with the trajectory of the cursor. Results showed that
      continuous visual feedback led to more precise movement end positions during
      practice than terminal visual feedback, but to less precise movements during open
      loop tests. This finding indicates that terminal visual feedback supports the
      development of a precise internal model of a new visuo-motor transformation.
      However, even terminal feedback of the cursor trajectory during practice did not
      result in an internal model, which includes appropriate curvatures of hand
      movements. STATEMENT OF RELEVANCE: This paper presents results on the influence
      of type of visual feedback on learning the complex motor skill of controlling a
      sliding lever. These findings contribute to the conceptual basis of optimised
      training procedures for the acquisition of sensori-motor skills required for the
      mastery of instruments utilised in minimally invasive surgery.

PMID- 21181588
TI  - A study of the difference between nominal and actual hand forces in two-handed
      sagittal plane whole-body exertions.
AB  - Given a task posture, changes in hand force magnitude and direction with regard
      to joint locations result in variations in joint loads. Previous work has
      quantified considerable vertical force components during push/pull exertions. The
      objective of this work was to quantify and statistically model actual hand forces
      in two-hand, standing exertions relative to the required nominal horizontal and
      vertical hand forces for a population of widely varying stature and strength. A
      total of 19 participants exerted force on a fixed handle while receiving visual
      feedback on the magnitude of force exerted in the required horizontal or vertical
      direction. A set of regression equations with adjusted R(2) values ranging from
      0.20 to 0.66 were developed to define actual hand force vectors by predicting off
      axis forces from the required hand force magnitude. Off-axis forces significantly
      increase the overall magnitude of force exerted in two-hand push/pull and up/down
      standing force exertions. STATEMENT OF RELEVANCE: This study quantifies and
      statistically models actual hand forces in two-hand, standing exertions.
      Inaccuracies in hand force estimates affect the ability to accurately assess task
      oriented strength capability. Knowledge of the relationship between nominal and
      actual hand forces can be used to improve existing ergonomic analysis tools,
      including biomechanical simulations of manual tasks.

PMID- 21181589
TI  - Low back injury risks during construction with prefabricated (panelised) walls:
      effects of task and design factors.
AB  - New technology designed to increase productivity in residential construction may
      exacerbate the risk of work-related musculoskeletal disorders (WMSDs) among
      residential construction workers. Of interest here are panelised (prefabricated)
      wall systems (or panels) and facilitating an ongoing effort to provide proactive
      control of ergonomic exposures and risks among workers using panels. This study,
      which included 24 participants, estimated WMSD risks using five methods during
      common panel erection tasks and the influences of panel mass (sheathed vs.
      unsheathed) and size (wall length). WMSD risks were fairly high overall; e.g. 34%
      and 77% of trials exceeded the 'action limits' for spinal compressive and shear
      forces, respectively. Heavier (sheathed) panels significantly increased risks,
      although the magnitude of this effect differed with panel size and between tasks.
      Higher levels of risk were found in tasks originating from ground vs. knuckle
      height. Several practical recommendations based on the results are discussed.
      STATEMENT OF RELEVANCE: Panelised wall systems have the potential to increase
      productivity in residential construction, but may result in increased worker
      injury risks. Results from this study can be used to generate future panel design
      and construction processes that can proactively address WMSD risks.

PMID- 21181590
TI  - Effect of initial horizontal object position on peak L5/S1 moments in manual
      lifting is dependent on task type and familiarity with alternative lifting
      strategies.
AB  - This study investigated whether the effects of initial horizontal object position
      on peak L5/S1 total moment (PTM) are affected by task type or familiarity with
      alternative lifting strategies during manual lifting. Nine subjects lifted low
      lying boxes from far and close initial horizontal positions in a typical
      laboratory lifting task (without any transportation of the load) and in a more
      realistic lifting task in which the box was transported to a location at a few
      metres distance. Subsequently, subjects were familiarised with alternative
      lifting strategies (e.g. shifting and tilting) and they then repeated the more
      realistic lifting task. Compared with the typical laboratory lifting task, the
      more realistic lifting task resulted in 6% larger PTMs for the close-positioned
      box. Familiarisation with alternative lifting techniques resulted in a 10%
      reduction in PTMs for the far-positioned box. As a result, the effect of initial
      horizontal box position on PTMs was smaller for the more realistic lifting task
      than for the typical laboratory lifting task and vanished after familiarisation
      with alternative lifting strategies. STATEMENT OF RELEVANCE: This study showed
      that the effect of horizontal box position on peak L5/S1 moments is dependent on
      the type of lifting task (comparing a typical laboratory simulated lifting task
      with a more realistic task involving carrying the load for a short distance) and
      familiarity with alternative lifting strategies. Therefore, it is recommended
      that back loading should be evaluated in a realistic simulation of the work
      situation or at the workplace itself.

PMID- 21181591
TI  - The between-day and inter-rater reliability of a novel wireless system to analyse
      lumbar spine posture.
AB  - Lumbar posture is commonly assessed in non-specific chronic low back pain
      (NSCLBP), although quantitative measures have mostly been limited to laboratory
      environments. The BodyGuardTM is a spinal position monitoring device that can
      monitor posture in real time, both inside and outside the laboratory. The
      reliability of this wireless device was examined in 18 healthy participants
      during usual sitting and forward bending, two tasks that are commonly provocative
      in NSCLBP. Reliability was determined using intraclass correlation coefficients
      (ICC), the standard error of measurement (SEM), the mean difference and the
      minimal detectable change (MDC90). Between-day ICC values ranged from 0.84 to
      0.87, with small SEM (5%), mean difference (<9%) and MDC90 (<14%) values. Inter
      rater ICC values ranged from 0.91 to 0.94, with small SEM (4%), mean difference
      (6%) and MDC90 (9%) values. Between-day and inter-rater reliability are essential
      requirements for clinical utility and were excellent in this study. Further
      studies into the validity of this device and its application in clinical trials
      in occupational settings are required. STATEMENT OF RELEVANCE: A novel device
      that can analyse spinal posture exposure in occupational settings in a minimally
      invasive manner has been developed. This study established that the device has
      excellent between-day and inter-rater reliability in healthy pain-free subjects.
      Further studies in people with low back pain are planned.

PMID- 21181592
TI  - Electromyography of the thigh muscles during lifting tasks in kneeling and
      squatting postures.
AB  - Underground coal miners who work in low-seam mines frequently handle materials in
      kneeling or squatting postures. To assess quadriceps and hamstring muscle demands
      in these postures, nine participants performed lateral load transfers in kneeling
      and squatting postures, during which electromyographic (EMG) data were collected.
      EMG activity was obtained at five points throughout the transfer for three
      quadriceps muscles and two hamstring muscles from each thigh. ANOVA results
      indicated that EMG data for nine of 10 thigh muscles were affected by an
      interaction between posture and angular position of the load lifted (p < 0.001).
      Muscles of the right thigh were most active during the lifting portion of the
      task (lifting a block from the participant's right) and activity decreased as the
      block was transferred to the left. Left thigh muscles showed the opposite
      pattern. EMG activity for the majority of thigh muscles was affected by the size
      of the base of support provided by different postures, with lower EMG activity
      observed with a larger base of support and increased activity in postures where
      base of support was reduced (p < 0.05). Thigh EMG activity was lowest in postures
      with fully flexed knees, which may explain worker preference for this posture.
      However, such postures are also associated with increased risk of meniscal
      damage. STATEMENT OF RELEVANCE: Kneeling and squatting postures are sometimes
      used for manual lifting activities, but are associated with increased knee injury
      risk. This paper examines the EMG responses of knee extensors/flexors to lifting
      in these postures, discusses the impact of posture and kneepads on muscle
      recruitment and explores the implications for work in such postures.

PMID- 21181593
TI  - Rapid determination of benzo(a)pyrene in processed meat and fish samples by
      second-derivative constant-energy synchronous fluorescence spectrometry.
AB  - A simple, rapid and cost-effective method has been established for the
      determination of the quantity of benzo(a)pyrene (BaP), one of the most
      carcinogenic polycyclic aromatic hydrocarbons (PAHs), in roasted, smoked and
      charcoal grilled foods. Second-derivative constant-energy synchronous
      fluorescence spectrometry (DCESFS) improves the spectral resolution and
      selectivity of the fluorescence method. By using this method, processed meat,
      fish and some other food samples were analysed without resorting to complex pre
      separation and purification procedures. The method was found to have a recovery
      of 97.7% +/- 4.3%. The limit of detection (LOD) for BaP was 0.14 ug kg-1, far
      below the regulatory limit (1.0 ug kg-1) for BaP in food samples specified by the
      European Union. A certified reference material (Coconut oil, BCR(r)-458) was used
      to confirm the validity of the proposed method. The results suggest that the
      measurements are in a good agreement with the certified BaP concentrations (5.4%
      deviation). The results obtained by the proposed method for analysing BaP in food
      samples correlated well with those obtained by GC/MS.

PMID- 21181594
TI  - Migration of melamine from can coatings cross-linked with melamine-based resins,
      into food simulants and foods.
AB  - Resins based on melamine-formaldehyde and related analogues such as methylolated
      melamine are used to cross-link coatings used inside food cans and on the metal
      closures of glass jars. Thirteen commercially coated cans and closures
      representing 80% of the European market were tested using simulants under
      realistic industrial heat-processing conditions for canned and jarred foods. The
      food simulants and the retort conditions used were 3% acetic acid for 1 h at 100 
      degrees C and 10% ethanol for 1 h at 130  degrees C. The highest migration level
      seen for melamine into simulant was 332 ug kg-1. There was no detectable
      migration of the melamine analogues cyanuric acid (<1 ug kg-1) or ammelide (<5 ug
      kg-1) from any sample. Twelve of the thirteen samples released no detectable
      ammeline (<5 ug kg-1) but the coating giving the highest release of melamine did
      also release ammeline at 8 ug kg-1 with the higher of the two process
      temperatures used. Migration experiments into food simulant and foods themselves
      were then conducted using two experimental coatings made using amino-based cross
      linking resins. Coated metal panels were exposed to the food simulant 10% (v/v)
      aqueous ethanol and to three foodstuffs under a range of time and temperature
      conditions both in the laboratory and in a commercial food canning facility using
      proprietary time and temperature conditions. The highest migration into a food
      was 152 ug kg-1 from the first coating processed for a long time at a moderate
      sterilisation temperature. The highest migration into simulant was also from this
      coating at 220 ug kg-1 when processed at 134  degrees C for 60 min, dropping to
      190 ug k-1 when processed at 123  degrees C for 70 min. Migration from the second
      coating was quite uniformly two to three times lower under all tests. These
      migration results were significantly higher than the levels of melamine
      extractable using 95% ethanol at room temperature. The experiments show that
      commercial canning and retorting can be mimicked in an acceptable way using
      laboratory tests with an autoclave or a simple pressure cooker. The results
      overall show there is hydrolytic degradation of the melamine cross-linked resins
      to release additional melamine. There is a strong influence of the temperature of
      heat treatment applied with foods or simulants but only a minor influence of time
      of heating and only a minor influence, if any, of food/simulant acidity.

PMID- 21181595
TI  - Screening methods for the detection of antibiotic residues in slaughter animals:
      comparison of the European Union Four-Plate Test, the Nouws Antibiotic Test and
      the Premi(r)Test (applied to muscle and kidney).
AB  - Microbial growth inhibition tests are widely used as the primary screening
      approach for the detection of antibiotic residues in slaughter animals. In this
      study we evaluated and compared the performance of the European Union Four-Plate
      Test (EU4pt), the Nouws Antibiotic Test (NAT), and a commercial ampoule test, the
      PremiTest (applied to both muscle and kidney), by parallel analysis of 735
      slaughter animals. The EU4pt only showed significant inhibition with two muscle
      samples containing 305 ug kg(-1) doxycycline and 648 ug kg(-1) tulathromycin,
      while an maximum residue limit (MRL) violation of 1100 ug kg(-1) sulfamethazine
      remained unnoticed. PremiTest-muscle only detected the sulfamethazine containing
      sample, all other (1.1%) suspect samples appeared false-positive results. The
      same test applied to kidney yielded 4.1% suspect samples, while the NAT screening
      (based on analysis of renal pelvis fluid) showed 4.9% suspect results. The vast
      majority of these samples contained tetracycline and/or aminoglycoside residues.
      PremiTest-kidney appeared to be more sensitive to aminoglycosides than the NAT
      screening, which failed to detect an MRL violation of 870 ug kg(-1) gentamicin in
      kidney. Detection of less than MRL levels of tetracycline residues by the NAT
      proved its suitability for this residue group. Whether PremiTest is sufficiently
      sensitive for accurate tetracycline detection in kidney remains doubtful,
      although changing over to kidney definitely improved the suitability of PremiTest
      for the detection of residues in slaughter animals.

PMID- 21181596
TI  - Survey of counterfeit melamine tableware available on the market in Thailand, and
      its migration.
AB  - A simple measurement of sample density by adopting the principles of buoyancy
      could help screen counterfeit melamine ware if the density was below 1.50 g cm-3.
      However, samples with a density exceeding 1.50 g cm-3 were not necessarily made
      from melamine formaldehyde. FTIR analysis showed that all counterfeit products
      were made of urea formaldehyde and coated on the food-contact side with melamine
      formaldehyde, a tactic probably intended to cover up the true product features.
      The overall migration of real and counterfeit melamine samples complied with both
      European Union and Thai regulations, as the exposure layers in both cases were
      melamine formaldehyde. Formaldehyde migration failed to comply with Thai
      standards, but this was not the case for European Union standards. However, the
      results showed a significant inconsistency between individual items of the same
      brand and between individual exposures of the same test specimen. This indicated
      the inherent inhomogeneity between individual items, which mainly resulted from
      the manufacturing process: for instance, insufficient temperature and time to
      obtain complete polycondensation of monomers. Therefore, it is recommended that
      constant surveillance be conducted on melamine articles available in the
      marketplace in terms of quality and safety.

PMID- 21181597
TI  - Long-term dietary exposure to lead of the population of Jiangsu Province, China.
AB  - Deterministic and probabilistic estimates of the chronic exposure to lead (Pb)
      for the inhabitants in Jiangsu Province, China, were performed. Pb contamination
      data were obtained from the national food contamination monitoring programme
      during 2001-2006 and 2600 samples from 38 commodities in Jiangsu were included.
      Food consumption data were from the national diet and nutrition survey conducted
      in 2002, including 3879 subjects aged 2-80 years and 185 children aged 2-6 years
      in Jiangsu. Contributions from 38 commodities were included in the calculations.
      Using the provisional tolerable weekly intakes (PTWI) divided into daily intakes
      (PTWI(d)) of 3.57 microg kg(-1) bw day(-1) in the risk assessment, exposures
      calculated by the deterministic approach for children and the general population
      were 77% and 43% of the PTWI(d), respectively, which were nearly similar to the
      mean intake calculation in the probabilistic approach. The percentage of people
      whose exposure level exceeded the PTWI(d) for children, the general population,
      urban population and rural population were 16%, 0.4%, 0.1%, and 0.5%,
      respectively. The 50th, 95th and 99th percentiles of Pb exposure for children
      were 2.6, 4.4 and 5.5 microg kg(-1) bw day(-1), respectively. Rice followed by
      wheat flour and bean products contributed most to the total Pb intake for both
      children and the general population. This study indicated that the Pb dietary
      exposure in Jiangsu Province, especially for children, would be a public health
      concern.

PMID- 21181598
TI  - Local perspectives on empowerment and responsibility in the new public health.
AB  - The new public health is compelling because it uses the discourse of empowerment
      and participatory methodologies to promote health citizenship, but it has also
      been criticized for reinforcing an individual locus of responsibility while
      overlooking the role of the state in providing healthy environments. Thus far,
      much of the discourse surrounding the new public has tended to be the purview of
      public health experts and professionals. This study uses the interpretive
      approach to health communication to understand how debates regarding rights and
      responsibilities inherent in the new public health are appropriated by six
      employees at two community-based organizations that provide support to HIV
      positive (HIV+) people in South India. I ask the question: How is the term
      "empowerment" understood by these individuals? Three primary dimensions of power
      emerged from my study: power from self-acceptance and inner strength, power from
      family and society, and power from self-reliance. In talking about empowerment,
      participants implicitly and explicitly made assumptions about who was responsible
      for health and health care; they argued that the individual and community were
      responsible for health, and reframed "rights" in terms of duty and citizenship.
      The discussion speculates on reasons for the heightened sense of personal
      responsibility, as well as implications it has for community health practice.

PMID- 21181599
TI  - The poetics of professionalism among dialysis technicians.
AB  - The vast majority of care for end-stage renal disease (ESRD) patients is provided
      by skilled (but not formally educated) paraprofessional technicians. Using
      Goffman's (1959) framing of the performance of self in everyday discourse, this
      study examines discourse from dialysis technicians and technical aides to explore
      these paraprofessionals' construction and performance of professional identity
      and professional communication within the context of an outpatient dialysis
      clinic. Themes of professionalism--individualized care, vigilance, teamwork, and
      emotion management--are illustrated via poetic transcription of interviews with
      technicians. I contend that such representation offers validity equal to that of
      traditional research accounts while embodying alternative representational
      strengths.

PMID- 21181600
TI  - Measuring social support for weight loss in an internet weight loss community.
AB  - Although overweight and obese individuals are turning to Internet communities for
      social support for weight loss, there is no validated online instrument for
      measuring the subjective social support experiences of participants in these
      communities. The authors' objective was to determine whether an online version of
      a validated paper questionnaire, the Weight Management Support Inventory, is
      appropriate for measuring social support among members of Internet weight loss
      communities. The authors administered the paper and online versions of the
      questionnaire in random, counterbalanced fashion to 199 members of a large
      Internet weight loss community. Scores for the paper and online versions were
      comparable in between-subjects and within-subjects comparisons. Convergent
      validity is suggested by the finding that participants who posted messages on
      Internet forums several times per day reported more social support than those who
      posted less frequently. However, the instrumental (tangible) support items did
      not load significantly on the instrumental support factor, suggesting that
      instrumental support is not relevant to the social support exchanged among
      participants in these communities. The authors conclude that the online, modified
      Weight Management Support Inventory, without items for instrumental support, is
      an appropriate instrument for measuring social support for weight loss among
      members of Internet weight loss communities.

PMID- 21181601
TI  - Obesity in the news: do photographic images of obese persons influence antifat
      attitudes?
AB  - News coverage of obesity has increased dramatically in recent years, and research
      shows that media content may contribute to negative public attitudes toward obese
      people. However, no work has assessed whether photographic portrayals of obese
      people that accompany news stories affect attitudes. In the present study, the
      authors used a randomized experimental design to test whether viewing
      photographic portrayals of an obese person in a stereotypical or unflattering way
      (versus a nonstereotypical or flattering portrayal) could increase negative
      attitudes about obesity, even when the content of an accompanying news story is
      neutral. The authors randomly assigned 188 adult participants to read a neutral
      news story about the prevalence of obesity that was paired with 1 of 4
      photographic portrayals of an obese adult (or no photograph). The authors
      subsequently assessed attitudes toward obese people using the Fat Phobia Scale.
      Participants in all conditions expressed a moderate level of fat phobia (M =
      3.83, SD = 0.58). Results indicated that participants who viewed the negative
      photographs expressed more negative attitudes toward obese people than did those
      who viewed the positive photographs. Implications of these findings for the media
      are discussed, with emphasis on increasing awareness of weight bias in health
      communication and journalistic news reporting.

PMID- 21181602
TI  - Dimensions of the Dysexecutive Questionnaire (DEX) examined using Rasch analysis.
AB  - Executive dysfunction is very broad term used to capture a range of interacting
      high-level cognitive, emotional and behavioural difficulties, commonly seen after
      acquired brain injury (ABI). Many argue that the concept of executive functioning
      should be subdivided into several separate dimensions. In this study we explore
      the dimensional structure of a tool designed to assess level of executive
      functioning, the Dysexecutive (DEX) Questionnaire (Burgess, Alderman, Wilson,
      Evans, & Emslie, 1996), in order to inform theoretical conceptualisations of
      executive functioning and improve measurement precision in rehabilitation
      centres. Rasch analysis was undertaken on the responses of 363 people with ABI to
      the DEX. Overall, the questionnaire did not perform as a unidimensional, interval
      level scale of executive functioning, suggesting that it measures more than one
      psychological construct. Most subscales previously proposed using factor
      analysis, including those suggested in the DEX manual, did not perform as
      unidimensional interval-level scales either. Several new subscales in keeping
      with theoretical conceptualisations of the different dimensions of executive
      functioning are proposed, alongside suggestions for revision of the wording and
      scoring of some of the items in the DEX. These results provide a platform for
      future evaluation of executive function rehabilitation programmes.

PMID- 21181603
TI  - How intensive does anomia therapy for people with aphasia need to be?
AB  - The intensity of aphasia therapy has been a key clinical question. The aim of
      this case-series study was to compare the outcome of intensive and non-intensive
      therapy in the relearning of words for people with aphasia. Eight participants
      took part in a study comparing the intensity of delivery of the therapy.
      Participants received two courses of the same therapy (each lasting 10 sessions)
      delivered either intensively or non-intensively. Therapy consisted of
      confrontation naming with progressive phonemic and orthographic cues. Post
      therapy assessments were carried out immediately after the study and one month
      later. Performance was also monitored during each therapy session. Immediately
      post-therapy, both types of therapy had improved naming accuracy considerably and
      there was no significant difference between the two interventions. One month
      later, seven out of eight participants showed a small yet significant difference
      in naming accuracy, favouring non-intensive over intense therapy. There were no
      differences in the learning patterns during the therapy sessions between the
      intensive and non-intensive therapies. For the majority of people with aphasia
      post-stroke, both intense and non-intense therapy for anomia leads to improved
      naming performance. Retention at one-month post therapy is relatively superior
      after non-intensive therapy.

PMID- 21181604
TI  - Embedded effort indicators on the California Verbal Learning Test - Second
      Edition (CVLT-II): an attempted cross-validation.
AB  - This study determined whether the logistic regression method that was recently
      developed by Wolfe and colleagues (2010) for the detection of invalid effort on
      the California Verbal Learning Test - Second Edition (CVLT-II) could be cross
      validated in an independent sample of 100 consecutively referred patients with
      traumatic brain injury. Although the CVLT-II logistic regression formula
      demonstrated a statistically significant level of agreement with results from the
      Word Memory Test, it was associated with an unacceptably high proportion of false
      positives. The component variables of the logistic regression were sensitive to
      length of coma but did not covary with psychosocial complicating factors (e.g.,
      unresolved prior psychiatric history) that were associated with a higher relative
      risk of failure of WMT validity criteria. It is concluded that the Wolfe et al.
      logistic regression should be used only with great caution in the context of
      clinical neuropsychological evaluations.

PMID- 21181605
TI  - Impact of Lodox Statscan on radiation dose and screening time in paediatric
      trauma patients.
AB  - INTRODUCTION: As part of the primary investigation, polytrauma patients arriving
      at our emergency department are examined in accordance with the Advanced Trauma
      Life Support (ATLS) rules, using the new Lodox Statscan (LS) digital low
      radiation imaging device. The aim of this study was to establish whether entrance
      and effective radiation doses using LS in children were comparable to those of
      paediatric Computed Radiography (CR) and to evaluate the duration of scanning for
      both techniques in young polytrauma patients. METHODS: 19 consecutive polytrauma
      patients aged <16 years who had LS imaging were included in this prospective
      analysis. For a comparison of our results, we put together an age-, size-, injury
      type- and ISS-matched group of young patients screened using paediatric
      Conventional Radiology (CR). Entrance, effective doses and mean duration of
      diagnostic imaging were recorded for both groups. RESULTS: Effective and entrance
      doses were higher in the LS group compared to the paediatric CR group (p<0.001).
      This might be partly due to the higher radiation dose necessary for lateral LS
      spine imaging, and also because with conventional radiography, only selected
      parts of the spine are imaged compared to the standard full spinal view with LS.
      Diagnostic imaging with LS required less time than paediatric CR (p=0.117).
      CONCLUSION: LS scanning will probably be a useful diagnostic tool for a range of
      paediatric clinical indications in the future. But only the future will show
      whether LS will survive in the face of low-dose radiation CT scanners and
      magnetic resonance imaging devices that may eventually completely replace
      conventional radiography.

PMID- 21181606
TI  - The outcome of expectant management of congenital cystic adenomatoid malformation
      of the lung.

PMID- 21181607
TI  - Safety of botulinum toxin for the treatment of children with chronic anal
      fissure.

PMID- 21181608
TI  - Tumoral calcinosis of the gluteal region in a 14-year-old girl with juvenile
      polyarthritis.

PMID- 21181610
TI  - [Familial non-polyposis colorectal carcinoma (Lynch syndrome) in Germany -
      analysis of information, advisory service and family screening].
AB  - BACKGROUND: Lynch syndrome is associated with an increased incidence of
      colorectal carcinomas and extracolonic neoplasms. Patients fulfilling the
      "Revised Bethesda criteria" or the Amsterdam Citeria I or II should be screened
      for DNA mismatch repair deficiency. Mutation carriers and high risk individuals
      should undergo intensified annual screening, as recommended by the S3 guideline
      for colorectal carcinoma. PATIENTS AND METHODS: All families of the Regensburger
      study group with a verified mutation were included in this study. Data
      acquisition was conducted by telephone interviews. We determined the number of
      family members who had been informed about the diagnosis and how many of them
      participated in the recommended screening program. Additionally, an information
      letter was sent to family members providing information about the opportunity of
      a predictive mutation analysis. RESULTS: 90 family members of 12 families with a
      total of 42 carcinomas and a mean age of tumor diagnosis of 41.3 years were
      included. At the beginning of the study 97.4 % of the family members were
      informed about the diagnosis. In the course of the study the number of family
      members participating in the mutation analysis increased from 29.5 % to 42.3 %.
      The number of index patients complying with the recommended screening program was
      over 90 %, in contrast to the number of family members which varied between 30 -
      60 %. CONCLUSIONS: Relatives of index patients are not sufficiently informed
      about the importance of predictive testing and the re-commended surveillance
      guidelines. An insufficient implementation of Lynch syndrome specific aspects of
      the S3-guideline can be assumed. For an improved implementation barriers of
      physicians' adherence must be systemically analyzed. It is essential for these
      high-risk families to establish and enforce awareness in order to create
      intensified surveillance.

PMID- 21181611
TI  - [Angiospastic occlusion of the superficial femoral artery by chronic ergotamine
      intake].
AB  - HISTORY AND CLINICAL FINDINGS: A 42- year old women with a long history of
      migraine presented with burning pain of the limbs and reduced walking distance.
      No risk factors for peripheral arterial occlusive disease were present. Her daily
      medication included an ergotamine-containing-combination (2 mg ergotamine
      tartrate, 100 mg caffeine daily). INVESTIGATIONS: On examination both limbs were
      found to be cool and pulseless below the knee. The peripheral Doppler pressure
      indicated a bilaterally reduced ankle-brachial index. Color-coded duplex
      sonography showed constricted vessels and long stenosis with a decreased echo
      from the wall of the left and a distal occlusion of the right femoral artery
      without atherosclerotic changes. A diagnosis of ergotism was made and an
      arteriography was omitted because of the typical findings. TREATMENT AND COURSE:
      A detoxication treatment was initiated and optional intravenous prostaglandine E1
      recommended if the condition did not improve. 23 days later the Doppler pressure
      and the Duplex sonography had become normal and showed spontaneous
      revascularization of the previously occluded right femoral artery, although
      collateral vessels were still detectable. CONCLUSION: Nowadays iatrogenic
      ergotism of the limbs is a rare diagnosis. An exact medical history and typical
      duplex sonographic findings confirm the diagnosis even if characteristic risk
      factors are missing. The first therapeutic measure in case of claudication is for
      ergotamine to be stopped. In case of critical ischaemia or gangrene immediate
      vasodilator therapy, e. g. with prostaglandine E1, is indicated.

PMID- 21181612
TI  - [42-year-old patient with diarrhea since 6 months].

PMID- 21181613
TI  - [Hypo- and hypernatremia].
AB  - Hyponatremia is an electrolyte disorder that is defined by a serum sodium
      concentration of less than 135 mmol/L. Hyponatremia occurs at a high incidence.
      It is commonly associated with mild to moderate mental impairment. Hypoosmolar
      hyponatremia occurs in the setting of plasma volume deficiency ("hypovolemia", e.
      g. after gastrointestinal fluid loss), liver cirrhosis and cardiac failure
      ("hypervolemic" hyponatremia) and syndrome of inappropriate antidiuretic hormone
      secretion ("euvolemic" hyponatremia). Excessive antidiuretic hormone and
      continued fluid intake are the pathogenetic causes of these hyponatremias.
      Whereas hypovolemic hyponatremia is best corrected by isotonic saline,
      conventional proposals for euvolemic and hypervolemic hyponatremia consist of the
      following: fluid restriction, lithium carbonate, demeclocycline, urea and loop
      diuretic. None of these nonspecific treatments is entirely satisfactory. Recently
      a new class of pharmacological agents - orally available vasopressin antagonists,
      collectively called vaptans - have been described. A number of clinical trials
      using vaptans have been performed already. They showed vaptans to be effective,
      specific and safe in the treatment of euvolemic and hypervolemic hyponatremia. In
      Europe the vaptanes are currently certified exclusively for the treatment of
      euvolemic hyponatremia. Hypernatremia is caused by a relative deficit of free
      water and often occurs in elderly patients, who have an impaired thirst mechanism
      or are unable to ask for water. The cornerstone of treatment is administration of
      free water to correct the relative water deficit.

PMID- 21181614
TI  - [Cholesterol homeostasis and cardiovascular risk].
AB  - Hypercholesterolemia is a major risk factor for cardiovascular diseases.
      Serumcholesterol concentrations are regulated by enteral absorption and hepatic
      synthesis. Statins inhibit the rate-limiting enzyme of endogenous cholesterol
      synthesis, HMG-CoA-reductase and reduce serum cholesterol concentrations as well
      as cardiovascular morbidity. Indirect evidence from smaller studies shows, that
      patients with high baseline cholesterol absorption may show only a small response
      to statin treatment in terms of cholesterol lowering. Moreover, evidence from
      recent clinical studies suggests that increased cholesterol absorption and
      decreased hepatic cholesterol synthesis is associated with an increased
      cardiovascular risk. This article reviews the current literature on this issue
      and suggests prospective clinical studies to analyze whether determination of the
      baseline relation of cholesterol synthesis and absorption may facilitate an
      individualized lipid lowering therapy to further reduce cardiovascular risk.

PMID- 21181615
TI  - [Interdisciplinary management of cutaneous adverse events of EGFR inhibitors and
      multityrosine kinase inhibitors in oncology].
AB  - Molecular targeted therapies - particularly epidermal growth factor receptor
      inhibitors (EGFRi) and multi tyrosine kinase-inhibitors (MTKi) - continually gain
      importance in oncology treatment. Adverse events differ greatly from those of
      conventional chemotherapy; especially cutaneous adverse events often constitute
      dose-limiting or therapy-limiting events. Knowledge of possible adverse events
      and close interaction between the dermatologist, the oncologist and the patient's
      family physician, a detailed patient education and a well-founded adverse event
      management are mandatory for the treatment with EGFRi and MTKi. Interdisciplinary
      outpatient clinics specialised on the treatment of these adverse events assist
      with the treatment of severe cases, the development of new therapeutic strategies
      and are essential for the concomitant treatment of patients treated with new
      targeted drugs within clinical trials.

PMID- 21181616
TI  - [Ethics, empiricism and uncertainty].
AB  - Accidents can lead to difficult boundary situations. Such situations often take
      place in the emergency units. The medical team thus often and inevitably faces
      professional uncertainty in their decision-making. It is essential to communicate
      these uncertainties within the medical team, instead of downplaying or overriding
      existential hurdles in decision-making. Acknowledging uncertainties might lead to
      alert and prudent decisions. Thus uncertainty can have ethical value in treatment
      or withdrawal of treatment. It does not need to be covered in evidence-based
      arguments, especially as some singular situations of individual tragedies cannot
      be grasped in terms of evidence-based medicine.

PMID- 21181617
TI  - ?

PMID- 21181618
TI  - [Estimation of postoperative pain after tonsillectomy in adults using QUIPS: an
      instrument to improve postoperative pain management].
AB  - BACKGROUND: Tonsillectomy leads to strong postoperative pain. Pain management
      often is not optimal after tonsillectomy. To date, there exists no clear
      guideline for pain management after tonsillectomy. METHODS: In a prospective
      study 65 tonsillectomy patients were examined at the first postoperative day
      within the QUIPS project. This allowed a standardised assessment of patients'
      characteristics, pain parameters, outcome and process parameters. The influence
      of these parameters on the patients' postoperative pain was estimated with
      univariate and multivariate statistic analysis. RESULTS: All patients report of
      constant slight pain during the first postoperative day after tonsillectomy.
      Although maximal pain intensity was moderate, overall, patients were satisfied
      with the pain management. Pain management did not result in relevant side
      effects. Younger patients suffered significantly more from maximal pain than
      older patients. The same was obvious for patients who needed pain killers already
      prior to surgery. Perioperative antibiotic treatment and specific counselling
      about the possibilities of postoperative pain management reduced pain intensity
      highly significant in univariate and multivariate analysis. Patients receiving
      opioids on the ward postoperatively had significantly less pain. DISCUSSION:
      QUIPS is a very good tool to evaluate the quality of postoperative pain
      management in one's own hospital. Next step, a detailed comparison to the best
      practise of other hospitals participating at QUIPS will follow in order to
      improve and standardize pain management for adult tonsillectomy patients.

PMID- 21181619
TI  - [The learning curve of registration in navigated skull base surgery].
AB  - BACKGROUND: Computer aided surgery (CAS) is advantageous in challenging
      procedures in head and neck surgery. It is not clear, if the application of CAS
      has to be trained to achieve reliable results. The learning curve of the
      registration of the patient's coordinates to prior acquired radiologic imagery
      was investigated. MATERIAL AND METHODS: 4 residents performed pair-point
      registrations on 5 anatomic specimens in an experimental wet lab. The residents
      were in the same year of education and had no experience in CAS procedures. After
      each registration the application error was evaluated by determining the target
      registration error (TRE). Pair point matching by skin glued external fiducials
      was compared with pair point matching by internal anatomical landmarks. RESULTS:
      The application accuracy was improved by increasing numbers of performed
      registrations (p<0.001, trendtest of Page). An inverse trend of the learning
      curve could be observed, the median TRE values improved from 3.3 mm in the first
      registration to 1.6 mm after the fifth registration. In comparison e. g. an
      experienced CAS-user can achieve submillimetric TRE values under wet lab
      conditions. Pair point matching by anatomical landmarks resulted in worse
      application accuracy initially and the learning curve was steeper than with
      external fiducial markers. CONCLUSION: There is a training effect in CAS
      interventions. Pair point matching results in sufficient application accuracy
      after training only.

PMID- 21181620
TI  - [Effects of D-DRG system on hospital financing on the example of
      septorhinoplasty].
AB  - INTRODUCTION: Since the introduction of DRGs (diagnosis related groups) 2004, the
      septorhinoplasty, regardless whether an open or closed approach is chosen or
      whether orthotopic cartilage or autologous cartilage is required and whether a
      complex deformity (patients with cleft palate) or post-traumatic deformities are
      treated in the adult all procedures are valued the same. The aim of the study was
      to investigate at a center for rhino-surgery the real effort for the different
      diseases and to assess the necessity of a new split in the DRG for
      septorhinoplasty. METHODS: Retrospective study of all patients, who were treated
      from January 2006 to December 2009 at the ENT Clinic of the University of Ulm
      with a septorhinoplasty/septal perforation closure in terms of duration of
      surgery and the material consumption. RESULTS: In the years 2006-2009 at the ENT
      Clinic in Ulm 705 septorhinoplasties were performed, 124 were revision surgeries,
      216 with ear cartilage and 35 with rib cartilage. In 66 cases nasal deformities
      due to cleft palate was treated. The duration of surgery of the different
      septorhinoplasties differed statistically significant from each other, also the
      material consumption/material costs. CONCLUSION: A re-organization of the DRG D
      37 can be justified with varying surgery time and material consumption for each
      operation type. A proposal is presented.

PMID- 21181621
TI  - [No Hearing Sensation after cochlear implantation despite successful objective
      measurement outcome].

PMID- 21181622
TI  - [German observational trial on secondary hyperparathyroidism therapy with
      cinacalcet (EARLY)].
AB  - BACKGROUND AND OBJECTIVES: The calcimimetic cinacalcet (Mimpara) was approved in
      the European Union in 2004 for treatment of secondary hyperparathyroidism (sHPT).
      This observational trial was conducted to investigate efficacy of cinacalcet and
      practices of sHPT treatment under routine clinical conditions. PATIENTS AND
      METHODS: 913 patients on maintenance hemodialysis were recruited from 136 German
      kidney centers. 662 patients who fulfilled the entry criteria of moderate to
      severe sHPT (intact parathyroid hormone, iPTH: 300 - 800 pg/mL or 32 - 85 pmol/l)
      were included in the trial. Primary objective was to investigate efficacy of
      cinacalcet in patients treated for at least 160 days (efficacy collective, N =
      555). The primary endpoint was defined as the percentage of patients with a iPTH
      within 150 - 300 pg/ml and a calcium-phosphate product (CaxP) <= 4.44 mmol (2)/l
      (2) (55 mg (2)/dl (2)) after 6 months of treatment. Further objectives were the
      course of calcium (Ca) and phosphate (P) as well as the use of phosphate binders
      and vitamin D in treatment of bone metabolism disorders. RESULTS: According to
      the predefined entry criteria none of the patients reached the combined target
      criterion for iPTH and CaxP at baseline. The mean initial iPTH and CaxP were
      530.0 +/- 134.3 pg/mL and 4.82 mmol (2)/L (2) (mean +/- SD) respectively. In
      spite of the unfavorable prognostic factors 25 % of the recruited patients met
      the combined target at the end of the trial. The mean reduction per patient for
      iPTH was 203.6 pg/mL [95 % confidence interval (CI) 183.3 - 224.0] and 0.69 mmol
      (2)/L (2) [95 %-CI 0.57 - 0.79] for CaxP. Ca and P were reduced by 5.3 % [95 %-CI
      4.3 - 6.3] and 5.5 % [95 %-CI 3.4 - 7.7], respectively. The mean daily dose of
      cinacalcet at trial end was 44.9 +/- 25.0 mg (mean +/- SD). At baseline, 90 % of
      patients who were analyzed for efficacy (n = 500/555) were treated with phosphate
      binders, 57 % were treated with a calcium-based phosphate binder (n = 317/555).
      The use of active Vitamin D (all active Vitamin D compounds) was recorded for 59
      % of the patients (n = 328/555). No relevant changes of these treatments were
      observed in the course of the trial. Tolerability of cinacalcet was good, 94
      adverse drug reactions were recorded in 57 of the 913 enrolled patients (6 %).
      CONCLUSIONS: One out of four patients reached the combined target of iPTH and
      CaxP with relatively low dose cinacalcet after 6 months of treatment. iPTH, Ca
      and P were reduced. The results confirm the high efficacy of cinacalcet in
      treatment of sHPT and underline the role of cinacalcet in the control of Ca and
      P.

PMID- 21181623
TI  - A chimeric flap model in dogs.
AB  - Prelamination is sometimes required for reconstruction of specialized organs. The
      purpose of this study was to create a chimeric flap model in dogs for
      prelamination. The anatomy of the deep and superficial caudal epigastric vessels,
      which supply the rectus abdominis muscle and superficial ventral fascia,
      respectively, were measured in 14 dogs. Their lengths were ~30 mm with the
      arteries averaging 1.4 mm and veins, 2.5 mm in diameter. These vessels shared a
      10-mm-long common trunk with the artery averaging 2 mm and the vein, 3.2 mm in
      diameter. Chimeric flaps were successfully raised in six dogs based on the common
      vascular trunk, and they remained well perfused 3 weeks after prelamination. The
      perfusion territory of the abdominal skin measured 25 cm long and 10 cm wide with
      methylene blue injection. This study suggests that the caudal epigastric system
      can be a suitable chimeric flap model in dogs.

PMID- 21181624
TI  - Vascular endothelial growth factor and its receptors are expressed in human nerve
      grafts.
AB  - Vascularization and angiogenicity of human nonvascularized nerve grafts in the
      second stage of facial reanimation were studied. Immunohistochemistry for
      endothelial markers (CD-31) and vascular endothelial growth factor (VEGF) and its
      receptors Flt-1 and Flk-1 was performed on distal end biopsies from 35 cross
      facial nerve grafts. In grafted nonvascularized nerve, density of vascular
      structures (also clearly immunopositive for VEGF and both receptors) showed a
      mean of 166 vessels (range 78 to 267) per unit area, corresponding to control
      values. In addition, VEGF was expressed in axons and perineural structures. In
      control samples, VEGF expression was low and occurred in the myelin sheath. In
      nerve grafts, expression of Flt-1 and Flk-1 (less intense) was seen in axons and
      perineural structures. A higher density of vessels was associated with lower VEGF
      expression (not significant). In short, expression of VEGF and its receptors is
      described in human nerve grafts and compared with basic histology and p75 nerve
      growth factor receptor expression of the nerve graft and functional outcome of
      patients.

PMID- 21181625
TI  - Evaluation of lower-limb arteries with multidetector computed tomography
      angiography prior to free flap surgery: a radioanatomic study.
AB  - In this study, we aimed to evaluate the vascular structures of the lower limb
      with multidetector computed tomography (CT) angiography and to reveal the
      importance of this method in preoperative planning of microsurgical
      transplantation. In 24 patients, lower-limb arteries were bilaterally evaluated
      with 16-detector spiral CT scanner in terms of patency, stenosis, or occlusion;
      maximal and minimal external diameters through their traces; and variations as
      well as length of the peroneal artery. The peroneal artery was absent
      unilaterally in two patients (4.3%). The mean maximal and minimal diameters were
      as 2.77 and 1.63, 2.92 and 1.75, and 2.72 and 1.50 mm for anterior and posterior
      tibial and peroneal arteries, respectively. The ranges of lengths of peroneal
      arteries were 50 to 117 mm. This valuable tool can provide detailed information
      about vascular and the remaining anatomic structures by means of its high
      resolution characteristics before planning free flap surgery.

PMID- 21181626
TI  - Femur-vastus intermedius-anterolateral thigh osteomyocutaneous composite chimeric
      free flap: a new free flap for the reconstruction of complex wounds.
AB  - Among the many bone and muscle flaps described in literature, several have stood
      the test of time and come forward as the preferred donor sites. Each has its own
      advantages and disadvantages. Yet another bone flap that has never been described
      in literature is introduced here. This is the vascularized femur bone flap based
      on the periosteal blood supply from the overlying vastus intermedius muscle. The
      vastus intermedius muscle free flap has the advantage of easy harvest, consistent
      vascular anatomy, long pedicle with large-caliber vessels, easy patient
      positioning, two-team approach, large surface area, minimal thickness, minimal
      donor site morbidity, and minimal functional loss. In this report, the femur
      vastus intermedius-anterolateral thigh osteomyocutaneous chimeric free flap based
      on the descending branch of the lateral circumflex femoral artery is used in the
      reconstruction of a complex composite defect of the lower extremity.

PMID- 21181627
TI  - [Development of DRG-reimbursement in hand surgery].
AB  - Since the introduction of Diagnosis Related Groups (DRGs) in 2004 in Germany the
      variables of remuneration changed continuously. Subjectively, reimbursement of
      DRG in hand surgery has a negative connotation among colleagues. We analyzed the
      development of reimbursement as well as the length of stay of inpatients over
      time in Hand Surgery considering various parameters concentrating on trends and
      correlation with macroeconomic parameters. The Top 10 diagnoses and therapies
      between 2004 and 2010 in our clinic were grouped and resulting DRGs with further
      linked data could be obtained. In addition to the Base Rate the Pay Base Rate
      (the effective Base Rate in a certain hospital considering compensatory payment)
      and the Z-Bax (the value that was reimbursed by the national health insurance per
      Base Rate) were used to calculate reimbursement. These were multiplied with the
      number of cases treated in 2009 obtaining the different total annual
      remuneration. The lower threshold of length of stay was constant over time, the
      middle length of stay became shorter in most of the Top 10 diagnoses whereas the
      upper threshold of length of stay was reduced to half of the time. The Base Rate
      and the Pay Base Rate increased by the end of the period but were outmatched by
      the Z-Bax as an indicator for the general level of reimbursement in Germany.
      Total remuneration between 2004 and 2009 was compared applying the Z-Bax and the
      Base Rate as well as the Pay Base Rate, respectively. For the latter, a surplus
      of 244 000 Euros and 311 000 Euros were calculated, respectively. No correlation
      with the Gross National Product or the Rate of Inflation could be found. The Pay
      Base Rate as the rate of effective payment in our clinic declined by 7% whereas
      the consumer price index gained 8,6% resulting in a loss of purchasing power of
      almost 16% in a 6-year period.

PMID- 21181628
TI  - Single-port transgastric access for repeated debridement of infected pancreatic
      necrotic tissue.

PMID- 21181629
TI  - Endoscopic closure of a post-traumatic pancreatic fistula with interventional
      radiology techniques.

PMID- 21181630
TI  - Percutaneous endoscopic gastrostomy placement during pregnancy in the critical
      care setting.

PMID- 21181631
TI  - [Congress Report - DKOU 2010: Think more security].

PMID- 21181632
TI  - [Parenthood as a (new) challenge for psychiatric services].

PMID- 21181634
TI  - [Psychiatric therapy in the native language].

PMID- 21181635
TI  - [The needs of mentally ill parents--a review of the literature].
AB  - BACKGROUND: Approximately 10 % of women and 6 % of men who become parents will
      experience mental health problems and a significant proportion of these have a
      severe psychiatric illness. PURPOSE: This paper provides a literature review of
      the needs of parents with severe mental illness. METHODS: Literature review.
      RESULTS: Mothers with severe mental illness have a wide range of complex health
      and social care needs in addition to their parenting needs, which must be
      addressed by services in pregnancy and postpartum to optimise outcomes. There is
      limited evidence on the needs of fathers with severe mental illness but they may
      have a greater number of needs than women, and a greater need for training in
      parenting skills than women suffering from severe mental illness. Parents with
      severe mental illness may experience stigma and discrimination, and fear
      accessing services due to fears of losing custody of their child. CONCLUSIONS:
      Although a significant proportion of parents with severe mental illness do lose
      custody, many can successfully parent if adequate support is available and needs
      are assessed and managed by a multi-disciplinary team.

PMID- 21181636
TI  - [Fatherhood and mental illness].
AB  - OBJECTIVE: Contrary to current theoretical debates on father roll and collective
      father representations, only few empirical studies have so far been done on the
      topic of fatherhood of psychiatric patients. The study at hand investigates the
      paternity rate, the frequency by which fathers actually live together with their
      children and other aspects commonly associated with fatherhood, of a cohort
      consisting of men who had been under psychiatric treatment. METHODS: 222-male
      patients who had been under psychiatric treatment in the first quarter of 2005
      were recruited for a survey on variables relevant to paternity. In addition to a
      descriptive statistical analysis a subgroup classification of fatherhood
      variables associated with other independent variables, i. e. primary diagnosis,
      severity of disease, migration background, relationship status and age was
      performed using the multivariate statistical methods of Exhaustive CHAID
      analysis. RESULTS: In total, of the 222 Patients we recruited for this study 74
      (33,3 %) were fathers. Of these, 44 were fathers to an underage child. 31 of
      these men actually lived in the same household as their child. The Exhaustive
      CHAID analysis was able to display different associations between the independent
      variables and the varied dependent aspects of fatherhood. Here, the independent
      variables "relationship status", "primary diagnosis" and "migration background"
      showed to be important. CONCLUSION: A paternity rate of approximately one third
      demonstrates the relevance of this subject matter. Specific options for
      treatment, support and therapy, which include the mothers of the patient's
      children and, where applicable, take their migrant background into consideration,
      need to be established.

PMID- 21181637
TI  - [Mentally ill women's subjective views on social context of desire for children.
      A qualitative approach].
AB  - OBJECTIVES: The desire for children among mentally ill women may be influenced by
      the perception of reproductive risks for the woman herself as well as for the
      potential child. Coping with these challenges is not only impacted by individual
      but also by social factors. Thus, the study aims at subjective views on various
      social aspects pertaining to the desire for children among this group including:
      (a) general context (b) partnership (c) family background (d) professionals and
      (e) genetic aspects in regard to desire for children. METHODS: In 2007, n = 15
      narrative-biographical interviews with childless women with mental illnesses aged
      26-42 years were analysed using a reconstructive approach. RESULTS/CONCLUSIONS:
      Participants focused on the development of stable social conditions and stable
      partnership as important prerequisites for desire for children. However, a mental
      illness might easily threaten the development of such stable conditions. It was
      emphasized that a partnership with a mentally ill partner can be both an
      important source of support as well as an additional burden due to the "doubled
      risk". Furthermore, it was reported that during contacts with mental health
      service providers, the desire for children is mostly restricted to the issue of
      adequate birth control. Some participants felt overburdened by bringing up this
      issue vis-a-vis professionals while some were afraid that their desire for
      children may become medicalised. Most participants were sceptical towards the use
      of (hypothetical) genetic techniques aiming at the prediction of a mental illness
      in the planned/unborn child.

PMID- 21181638
TI  - Leg strength and the VO2 max of older men.
AB  - The purpose of the study was to determine if leg strength limits VO2 max and the
      ability to reach a plateau during VO2 max test in older men during cycle
      ergometry. Men aged 70-80 years were randomly selected into a strength training
      (ST, n=12) 3 times weekly for 16 weeks, followed by 4 weeks detraining or a non
      training control group (C, n=12). Leg strength and VO2 max were assessed every 4
      weeks for 20 weeks; body composition and cardiac function were assessed before
      and after 16 weeks training and after 4 weeks detraining. Leg strength, upper leg
      muscle mass (ULMM), arterial-venous O2 difference (a-v O2 difference) and VO2 max
      increased in the ST group (95+/-0.6%, 7+/-0.7%. 6.2+/-0.5% and 8+/-0.8%,
      respectively; P<0.05) after 16 weeks training. After 4 weeks detraining, gains in
      ULMM (50%) and strength (75%) were retained, but VO2 max and a-v O2 difference
      returned to pre-training levels. There was no change in the ability of the
      participants to reach a plateau during VO2 max testing over the 20-week study.
      These findings indicate that leg strength may not limit either VO2 max or the
      ability to plateau during VO2 max tests in older men during cycle ergometry.

PMID- 21181639
TI  - Calf stretching in non-weight bearing versus weight bearing.
AB  - Limited ankle dorsiflexion passive range of motion (DF PROM) has been associated
      with lower extremity overuse injuries. Therefore, clinicians often prescribe
      stretching exercises to increase ankle DF PROM. However, there is limited
      evidence to indicate if any particular gastrocnemius stretching exercise results
      in greater improvement in DF PROM. The aim of this study was to determine if
      gastrocnemius stretching in non-weight bearing (NWB) or weight bearing (WB)
      results in a greater increase of ankle DF PROM. 28 healthy volunteers, aged 18-55
      years, who exhibited less than 10 degrees of ankle DF PROM completed the study.
      Participants were randomized into 2 stretching groups: NWB and WB. Both groups
      completed a 3-week home gastrocnemius stretching program, consisting of 5
      repetitions held for 30 s each, 2 times daily. Participants' ankle DF PROM was
      measured with a blinded standard goniometer in NWB and WB positions before and
      after participation in a 3-week home gastrocnemius stretching program. Two 3-way
      mixed model ANOVAs demonstrated no significant difference in ankle DF PROM
      between the NWB and WB groups for either the NWB measurement condition (p=0.49)
      or WB measurement condition (p=0.86). Gastrocnemius stretching exercises
      performed in NWB or WB were equally effective in increasing ankle DF PROM.

PMID- 21181641
TI  - [Bronchopulmonary sequestration as a cause for recurrent pneumonia].

PMID- 21181642
TI  - [Pulmonary hypertension due to chronic lung disease. Recommendations of the
      Cologne Consensus Conference 2010].
AB  - The 2009 European Guidelines on Pulmonary Hypertension did not cover only
      pulmonary arterial hypertension (PAH) but also some aspects of pulmonary
      hypertension (PH) in chronic lung disease. The European Guidelines point out that
      the drugs currently used to treat patients with PAH (prostanoids, endothelin
      receptor antagonists and phosphodiesterase-5 inhibitors) have not been
      sufficiently investigated in other forms of PH. Therefore, the European
      Guidelines do not recommend the use of these drugs in patients with chronic lung
      disease and PH. This recommendation, however, is not always in agreement with
      medical ethics as physicians feel sometimes inclined to treat other form of
      pulmonary hypertension which may affect quality of life and survival of these
      patients in a similar manner. In June 2010, a group of German experts met in
      Cologne, Germany, to discuss open and controversial issues surrounding the
      practical implementation of the European Guidelines. The conference was sponsored
      by the German Society of Cardiology, the German Society of Respiratory Medicine
      and the German Society of Pediatric Cardiology. One of the working groups was
      dedicated to the diagnosis and treatment of PH in patients with chronic lung
      disease. The recommendations of this working group are summarized in the present
      paper.

PMID- 21181643
TI  - [Anxiety and depression in the elderly: results of a regional examination].
AB  - AIM: The aim of this study was to determine the point prevalence of anxiety,
      depression and a mixed form of anxiety and depression in people older than 54
      years. METHOD: A cross-section study by postal questioning using HADS-D was
      carried out. RESULTS: In total, 24.8% of the examined population group reported
      about having anxiety, depression or a mixed form of both - depression: 12.7%
      (men: 5.1%, women: 7.6%), anxiety: 4% (men: 1.5%, women: 2.5%), mixed form: 8.1%
      (men: 2.5%, women: 5.5%). There was no significant statistical difference between
      men and women in severity of the examined psychological disorders. However, the
      mean scores in men as well as in women were higher with multiple psychological
      stress factors than with single psychological stress. Women were significantly
      more affected by the mixed form than men (chi (2)=5.2; p=0.02). There were
      positive correlations between age and seriousness of depression in the mixed form
      in women (r=0.62; p=0.001). CONCLUSION: In comparison, depression in older people
      develops 3 times and anxiety 2 times more often than in the general population;
      the sex ratio (men:women) in the general population is 1:2 for depression and
      anxiety; in the present study the ratio is almost 2:3.

PMID- 21181644
TI  - [Amenable mortality in Germany: spatial distribution and regional
      concentrations].
AB  - AIM: The aim of this study is to identify small areas in Germany burdened by
      exceptionally high rates of amenable mortality using the 439 counties as unit of
      analysis. METHODS: To overcome shortcomings of conventional mortality measures,
      we construct an indicator for amenable mortality (AM) which captures deaths that
      should not occur given current medical knowledge and technology. We age
      standardize individual-level data on mortality for the years 2000-2004 and plot
      the distribution of disease-specific AM on country maps. We consider deaths
      following ischaemic heart disease, cerebrovascular diseases, hypertension,
      diseases of the liver, traffic accidents, several cancer types and 24 other
      diseases that are classified as amenable to health care. The data is taken from
      the causes-of-death statistics (provided by Destatis). RESULTS: AM significantly
      differs between small areas within and between German federal states
      (Bundeslaender). Breast cancer and lung cancer in men are the most common AM
      causes in Germany. The often discussed mortality-gap between East and West
      Germany is predominantly driven by differences in amenable deaths following
      cardiovascular diseases. However, the maps of most carcinogenic deaths show a
      north-south gradient rather than an east-west difference.

PMID- 21181645
TI  - [Regional and individual factors of stress experience in Germany: results of a
      representative survey with the perceived stress questionnaire (PSQ)].
AB  - AIM: The aim of the present study was to define, besides prevalence data,
      regional and individual factors of stress experience in a representative sample
      of the German general population. METHODS: Regional factors were examined
      separately by federal state and the size of the political location. Individual
      factors were defined according to the severity of the stress experience as well
      as on the basis of central social factors such as family state, profession and
      earnings. The Perceived Stress Questionnaire (PSQ), a validated, self-evaluation
      process for recording a subjective representation of frequency estimates of
      stress experiences was used. Data acquisition was carried out by a market
      research institute in a multi-topic questionnaire (N=2,552). Households were
      selected by the random route procedure, target persons were also selected at
      random. RESULTS: The prevalence rate for an elevated stress experience was 14.5%,
      that for a very high stress experience 3.1% of the sample. People without
      education exhibited the highest rates of stress experience (36.8%), followed by
      the unemployed (30.6%). Individual and social factors that favour an increased
      stress experience are a subjectively poor state of health (OR: 3.42) or belonging
      to the lower social economic status (OR: 1.30). Furthermore, there are
      indications of regional factors such as size of the location as well as
      differences between the individual federal states. An east-west comparion did not
      show any significant differences with regard to stress experiences. CONCLUSION:
      In the light of the illness burden associated with chronic stress situations,
      preventative measures in cases of unemployment or low level of education should
      be given priority.

PMID- 21181646
TI  - [Value of distal gastrectomy as a remedial operation for failed fundoplication].
AB  - BACKGROUND: Failure of conventional antireflux surgery is a challenging problem.
      This study aims at defining the role of distal gastrectomy with Roux-en-Y
      diversion in the treatment of failed fundoplication. MATERIAL AND METHODS: This
      report reviews the indications and results of 26 patients who underwent
      revisional antireflux surgery in our department. Distal gastrectomy and Roux-en-Y
      reconstruction were performed in 6 patients (group a), refundoplication in 15
      (group b), and re-hiatoplasty in 5 patients (group c). RESULTS: Group a patients
      had the longest history (p = 0.001) and the highest number of previous operative
      procedures (p = 0.001). In contrast, hospital stay was longer and postoperative
      morbidity was higher after distal gastrectomy (p = n. s.). At follow-up, symptom
      improvement was achieved most reliably after distal gastrectomy (groups a-c:
      100%, 78.6%, and 60% of patients; p = n. s.). CONCLUSION: Distal gastrectomy with
      Roux-en-Y diversion is a safe and reliable surgical option for selected patients
      after failed fundoplication. Distal gastrectomy with Roux-en-Y diversion is a
      reliable surgical option for selected patients after failed fundoplication.
      Despite a higher morbidity, this procedure represents an important addition to
      the surgical armamentarium, particularly in patients with a history of multiple
      previous interventions.

PMID- 21181647
TI  - [Cascade stomach - a rare cause of gastric pseudoobstruction].

PMID- 21181649
TI  - In vivo local co-delivery of recombinant human bone morphogenetic protein-7 and
      pamidronate via poly-D, L-lactic acid.
AB  - The effects of bone anabolic agents such as bone morphogenetic proteins (BMPs)
      have the potential to be augmented by co-treatment with an anti-catabolic such as
      a bisphosphonate. We hypothesised that the effects of bisphosphonates on BMP
      induced bone anabolism would be dose dependent, and we aimed to test this in a
      small animal model. Agents were delivered locally using a biodegradable poly-D, L
      lactic-acid (PDLLA) polymer delivery system. Recombinant human BMP-7 (25 ug) was
      tested with a range of doses of the bisphosphonate pamidronate (0.02 mg, 0.2 mg
      and 2 mg local PAM; 0.3 mg/kg and 3 mg/kg thrice-weekly systemic PAM) versus BMP
      7 alone. Polymer pellets were surgically implanted in the hind limbs of female
      C57BL6/J mice (8-10 week) and ectopic bone nodules were harvested at 3 and 8
      weeks post-operatively. At 3 weeks, local low dose PAM (0.02 mg) induced a 102%
      increase in rhBMP-7 induced bone volume (p<0.01) as measured by miroCT, and this
      was comparable to systemic PAM (0.3 mg/kg thrice-weekly). In contrast, local high
      dose PAM (2 mg) resulted in a 97% decrease in bone volume (p<0.01). Radiography
      and histology indicated that the polymer vehicle was still largely present at 8
      weeks indicating inefficient biodegradation. This is the first study to validate
      the utility of local co-delivery of BMP/bisphosphonate via biodegradable polymer
      and supports the continued refinement of more advanced bioresorbable delivery
      systems for clinical applications.

PMID- 21181650
TI  - Transforming US Army trauma care: an evidence-based review of the trauma
      literature.
AB  - The US Army has been charged to transform to meet the demands of current and
      anticipated near-future combat needs, covering a full spectrum of military
      operations. The US Army combat trauma care system was created to deliver combat
      casualty care in a variety of situations and has been adapted to meet the needs
      of such care in both Operations Enduring Freedom and Iraqi Freedom. Questions
      related to our current system include the use and positioning of medical
      evacuation assets, the type of training for our trauma care providers, the
      positioning of these providers in proximity to the battlefield, and the type of
      units most suited to the wide variety of medical operations required of today's
      military medical team. The review was performed to evaluate available information
      in light of anticipated future needs to ensure preparedness. We reviewed trauma
      literature regarding the areas of civilian trauma systems, military trauma
      systems, presurgical trauma care, medical evacuation times, and the medical
      evacuation system. Among the conclusions drawn from the reviewed data include the
      following: regional trauma systems improve outcomes in significantly-injured
      patients; rural trauma care as part of a trauma system yields improved results
      compared to nontrauma hospitals and comparable results to those at a higher level
      center; and delivery of advanced trauma life support care has the potential to
      extend the period of time of safe medical evacuation to surgical capabilities.
      These lessons are used to discuss components of an improved system of trauma
      care, flexible for the varied needs of modern battlefield trauma and adaptable to
      provide support for anticipated future conflicts.

PMID- 21181651
TI  - Experience with mild traumatic brain injuries and postconcussion syndrome at
      Kandahar, Afghanistan.

PMID- 21181652
TI  - The road to recovery and rehabilitation for injured service members with limb
      loss: a focus on Iraq and Afghanistan.
AB  - Amputation of an extremity due to traumatic injury or a vascular occlusive
      disease is a life-altering event that occurs when limb salvage is not possible.
      While an amputation is viewed as a life saving procedure clinically, limb
      deficiency may result in an immediate loss in social, physical and financial well
      being for the patient. Military personnel returning from Operation Enduring
      Freedom and Operation Iraqi Freedom face unique challenges due to short residual
      limbs, unplanned amputations, high incidences of multiple limb loss, and
      accustomed activity levels prior to an amputation. The primary rehabilitation
      goal for these individuals is to provide them with an expedited recovery and
      progressive reintroduction into the civilian or active duty population. It is the
      purpose of this review to discuss the most frequent rehabilitation hardships
      service members endure following combat related trauma and future of prosthetic
      limb technology.

PMID- 21181653
TI  - Family advocacy: a program to support an expeditionary army.

PMID- 21181654
TI  - Increasing our access to care: a view from middle management.

PMID- 21181655
TI  - Access to care initiatives.

PMID- 21181656
TI  - Case study: realignment of US Army medical activity, Heidelberg assets during US
      Army Europe transformation-driven health clinic closures.

PMID- 21181657
TI  - Evaluating the impact of investments in information technology on structural
      inertia in health organizations.
AB  - Structural inertia is the overall capacity of an organization to adapt within a
      market environment. This paper reviews the impact of healthcare investments in
      information management/information technology (IM/IT) on the strategic management
      concept of structural inertia. Research indicates that healthcare executives
      should consider the relative state of structural inertia for their firms and
      match them with potential IM/IT solutions. Additionally, organizations should
      favorably consider IM/IT solutions that are comparatively less complex.

PMID- 21181658
TI  - Nutritional care of detained persons in Operation Iraqi Freedom.

PMID- 21181668
TI  - How science and technology will enhance medical education and training by the
      year 2039.

PMID- 21181669
TI  - Effects of using human patient simulator versus a CD-ROM on learning the
      management of patients exposed to chemical agents.
AB  - INTRODUCTION: Very little prospective, randomized, experimental research exists
      on the use of simulation as a teaching method, and no studies have compared the
      effects of 2 strategies of using the Human Patient Simulator (HPS) and a CD-ROM
      on the management of patients exposed to chemical agents. METHODS: A prospective,
      pretest-posttest experimental, mixed design (within and between) was used to
      determine if there were statistically significant differences between educational
      strategies using HPS, CD-ROM, and a control group in the care of patients exposed
      to chemical agents. Care was operationally defined as the score on the Management
      of Chemical Warfare Patients Performance (MCWPP) instrument. Participants
      included active duty and reserve military nurses (n=92). They were randomly
      assigned to one of 3 teaching groups: HPS (n=30), CD-ROM (n=31), or a control
      group (n=31). RESULTS: Analysis of variance and a Tukey post-hoc test were used
      to analyze the data. The means on MCWPP instrument were as follows: HPS (pretest:
      mean=65.13, SD +/- 8.9; posttest mean=73.0, SD +/- 8.6); CD-ROM (pretest:
      mean=67.74, SD +/- 11.18, posttest mean=65.67, SD +/- 10.82); control (pretest:
      mean=68.51 SD +/- 8.5; posttest mean=62.6, SD +/- 8.6). There were no significant
      differences between the groups on the pretest (P=.363), but there were
      significant differences on the posttest (P=.001). Post-hoc analyses indicated the
      HPS group performed better than the CD-ROM group (P=.017) and the control group
      (P=.000). There was no significant difference between the CD-ROM and control
      groups (P=.485). CONCLUSION: Based on the results of this study, the HPS is more
      effective than the CD-ROM in teaching nurses about the care of patients exposed
      to chemical agents.

PMID- 21181670
TI  - Training forward surgical teams: do military-civilian collaborations work?
AB  - The US Army and the Ryder Trauma Center (Jackson Memorial Hospital, Miami,
      Florida) teamed up to provide a training environment (ie, the Army Trauma
      Training Center) in which forward surgical teams can attend to gain critical
      teamwork and trauma technical skills to prepare for deployment to Iraq or
      Afghanistan. The purpose of this study was to gather trainee reactions to the
      military-civilian collaboration provided at ATTC after deployment to Iraq or
      Afghanistan. METHODS: Survey respondents were 135 US Army personnel (an
      approximately 50% response rate) who participated in the ATTC 2-week team
      training program between January 2005 and June 2007. The survey asked questions
      pertaining to their experience in the resuscitation unit and patient contact at
      the trauma center. RESULTS: Over 90% of participants agreed or strongly agreed
      that training in the resuscitation area was beneficial. A majority of
      participants also agreed or strongly agreed that the patient contact experience
      was sufficient (78.5%), was a good learning opportunity (90%), and that the
      experience was a good opportunity to apply what they had learned in their
      classroom training (over 80%). Areas of suggested improvement included the
      importance of clarifying roles between the ATTC trainees and the Ryder Trauma
      Center residents and interns. Trainees would have preferred an extension of the
      training as a whole, as they felt it was rushed in order to fit all training
      opportunities into the 2 weeks that they were in Miami. Finally, trainees noted
      the lack of injuries admitted to the trauma center which replicate injuries
      caused by blasts (ie, improvised explosive devices). CONCLUSIONS: The results of
      our efforts indicate that military-civilian collaborations do in fact work and
      are beneficial to both military and civilian medical providers. The opportunity
      to perform as a team in their respective roles, to respond to a variety of actual
      trauma patients, and access to civilian medical providers were beneficial. As
      mentioned, such collaborations are not without limitations. The good news is that
      most of the identified limitations will be corrected to ensure trainees get the
      best possible experience possible.

PMID- 21181671
TI  - Veterinary surveillance laboratories: developing the training program.
AB  - The increased need and demand for onsite, frequent, rapid, and portable food and
      bottled water testing for indicators of microbiological and chemical agents led
      to the deployment of 2 laboratory veterinary equipment sets. A Surveillance Food
      Laboratory Program (SFLP) was developed to allow Veterinary Corps commanders to
      establish targeted testing programs to enhance food safety and wholesomeness,
      along with faster responses to food defense, suspected foodborne illness, and
      food/water risk assessment missions. To support the deployment of the veterinary
      equipment sets and the SFLP, 2 new functional courses were developed by the
      Department of Veterinary Science. The Surveillance Food Laboratory Technician
      Course teaches essential technical skills that include sample processing, assay
      methodologies, results review, and interpretation of results produced by these
      laboratories. The Surveillance Food Laboratory Manager Course, developed for
      designated managers of the laboratories and laboratory programs, teaches the
      skills critical to ensuring proper surveillance laboratory oversight, testing,
      evaluation of results, risk communication, and response to presumptive positive
      results produced by the laboratories. Together, the courses allowed for the
      successful deployment of the unique veterinary equipment sets, resulting in
      development of fully operational surveillance laboratories in support of food
      protection missions in every major theater of operations.

PMID- 21181672
TI  - Leveraging affective learning for developing future airmen.

PMID- 21181673
TI  - Problem-based learning preparation for physician assistant faculty.
AB  - This study explores facilitator preparation for a physician assistant problem
      based learning (PBL) program. A qualitative study approach was used to
      investigate the experiences of 7 faculty members from 2 separate physician
      assistant PBL programs within the United States. Data was collected through
      interviews using open-ended questions that were recorded and analyzed. The
      results revealed important themes related to topics that addressed the faculty
      participants' personal experiences when first beginning this method of teaching.
      Issues addressed included the facilitator's outlook towards PBL, previous
      experiences which helped to make a smoother transition into their teaching
      position, approaches that assisted in preparing faculty and students to teach and
      learn in a PBL program, academic resources referenced by faculty members, and the
      use of nonclinical tutors in a physician assistant PBL program.

PMID- 21181674
TI  - Critical thinking skills: do we have any? Critical thinking skills of faculty
      teaching medical subjects in a military environment.

PMID- 21181675
TI  - Assessment-based instruction.

PMID- 21181677
TI  - Understanding the leadership and cultural dimensions of strategic healthcare
      policy-making in Iraq.

PMID- 21181676
TI  - If you want to know why students fail, just ask them.
AB  - One method to discover possible reasons why individuals fail academic training is
      to ask them. However, self-report information can be difficult to trust,
      especially if students are perceived as having something to lose if they are
      honest. The purpose of this study was to identify potential reasons students fail
      (or do well) in their training as reported by 4 groups: those who failed the
      program (F) (n=28) and a peer (F-P) (n=28); and those who passed with a grade of
      B or above (P) (n=101) and one of their peers (P-P) (n=32). Statistical analysis
      included chi-square test statistics and t tests with a P < .05. Only findings
      considered "external" to students are included here, including class structure
      and schedule, instructors and teaching, support systems, and sleep. Few
      differences were found between peer reports and self reports by students who
      passed or students who failed their program. On the positive side, both P and F
      students indicated they could get individual attention even with large classes,
      having good support systems, and bonding well with their unit. On the negative
      side, P and F students reported difficulty staying focused during long class
      hours, and F students felt teaching methods made it difficult to succeed and
      struggled with the fast pace of the course (P < .05). More than half of all
      students reported sleeping between 5 and 6 hours per night, but those who failed
      more often reported sleeping only 3 to 4 hours per night (P < .05). These
      findings highlight areas of organizational strength, as well as areas of
      difficulty for students, which will permit administrators to set goals and
      perhaps tailor their programs to reduce attrition.

PMID- 21181678
TI  - The school for Advanced Military Studies: an untapped resource for the Army
      Medical Department.

PMID- 21181679
TI  - Another way.

PMID- 21181680
TI  - Surgery under extreme conditions in the aftermath of the 2010 Haiti earthquake:
      the importance of regional anesthesia.
AB  - The 12 January 2010 earthquake that struck Port-au-Prince, Haiti caused >200,000
      deaths, thousands of injuries requiring immediate surgical interventions, and 1.5
      million internally displaced survivors. The earthquake destroyed or disabled most
      medical facilities in the city, seriously hampering the ability to deliver
      immediate life- and limb-saving surgical care. A Project Medishare/University of
      Miami Miller School of Medicine trauma team deployed to Haiti from Miami within
      24 hours of the earthquake. The team began work at a pre-existing tent facility
      in the United Nations (UN) compound based at the airport, where they encountered
      225 critically injured patients. However, non-sterile conditions, no means to
      administer oxygen, the lack of surgical equipment and supplies, and no
      anesthetics precluded the immediate delivery of general anesthesia. Despite these
      limitations, resuscitative care was administered, and during the first 72 hours
      following the event, some amputations were performed with local anesthesia.
      Because of these austere conditions, an anesthesiologist, experienced and
      equipped to administer regional block anesthesia, was dispatched three days later
      to perform anesthesia for limb amputations, debridements, and wound care using
      single shot block anesthesia until a better equipped tent facility was
      established. After four weeks, the relief effort evolved into a 250-bed, multi
      specialty trauma/intensive care center staffed with >200 medical, nursing, and
      administrative staff. Within that timeframe, the facility and its staff completed
      1,000 surgeries, including spine and pediatric neurological procedures, without
      major complications. This experience suggests that when local emergency medical
      resources are completely destroyed or seriously disabled, a surgical team staffed
      and equipped to provide regional nerve block anesthesia and acute pain management
      can be dispatched rapidly to serve as a bridge to more advanced field surgical
      and intensive care, which takes longer to deploy and set up.

PMID- 21181681
TI  - Editorial comments--Surgery under extreme conditions in the aftermath of the 2010
      Haiti earthquake.

PMID- 21181682
TI  - Changes in mortality rates and humanitarian conditions in Darfur, Sudan 2003
      2007.
AB  - The Darfur region of Sudan has been an intense focus of humanitarian concern
      since rebellions began there early in 2003. In 2004, the US Secretary of State
      declared that conflict in Darfur represented genocide. Since 2003, many sample
      surveys and various mortality estimates for Darfur have been made. Nonetheless,
      confusion and controversy surrounding mortality levels and trends have continued.
      For this project, results were reviewed from the highest quality field surveys on
      mortality in Darfur conducted between 2003 and 2008. Trend analysis demonstrated
      a dramatic decline in mortality over time in Darfur. By 2005, mortality levels
      had fallen below emergency levels and have continued to decline. Deaths directly
      due violence have declined as a proportion of all of the deaths in Darfur.
      Declining mortality in Darfur was not associated with other proximate
      improvements in well-being, such as improved nutrition. Without large-scale,
      humanitarian intervention, continuing high rates of mortality due to violence
      likely would have occurred. If mortality had continued at the high rate
      documented in 2004, by January 2009, there would have been 330,000 additional
      deaths. With the humanitarian assistance provided through the United Nations and
      non-governmental organizations, these people are alive today. A focus on excess
      deaths among noncombatants may draw attention away from other needs, such as
      establishing better security, improving service delivery to the displaced, and
      advocating for internally displaced persons to be reached today and to re
      establish their lives and livelihoods tomorrow.

PMID- 21181683
TI  - Community assessment for public health emergency response following Hurricane Ike
      -Texas, 25-30 September 2008.
AB  - INTRODUCTION: On 13 September 2008, Hurricane Ike made landfall near Galveston,
      Texas, resulting in an estimated 74 deaths statewide and extensive damage in many
      counties. The Texas Department of State Health Services, US Public Health
      Service, and the Centers for Disease Control and Prevention conducted assessments
      beginning 12 days following hurricane landfall to identify the public health
      needs of three affected communities. The results of the assessment are presented,
      and an example of a type of public health epidemiological response to a disaster
      due to a natural hazard is provided. METHODS: A one-page questionnaire that
      focused on household public health characteristics was developed. Using a two
      stage cluster sampling methodology, 30 census blocks were selected randomly in
      three communities (Galveston, Liberty, and Manvel, Texas). Seven households were
      selected randomly from each block to interview. RESULTS: The assessments were
      conducted on 25, 26, and 30 September 2008. At the time of the interview, 45%
      percent of the households in Galveston had no electricity, and 26% had no regular
      garbage collection. Forty-six percent reported feeling that their residence was
      unsafe to inhabit due to mold, roof, and/or structural damage, and lack of
      electricity. Sixteen percent of households reported at least one member of the
      household had an injury since the hurricane. In Liberty, only 7% of the household
      members interviewed had no access to food, 4% had no working toilet, 2% had no
      running water, and 2% had no electricity. In Manvel, only 5% of the households
      did not have access to food, 3% had no running water, 2% had no regular garbage
      collection, and 3% had no electricity. CONCLUSIONS: Post-Ike household-level
      surveys conducted identified the immediate needs and associated risks of the
      affected communities. Despite the response efforts, a high proportion of
      households in Galveston still were reportedly lacking electricity and regular
      garbage pickup 17 days post-storm. The proportion of households with self
      reported injury in Galveston suggested the need to enhance public education on
      how to prevent injuries during hurricane cleanup. Galveston public health
      officials used the assessment to educate local emergency and elected officials of
      the health hazards related to lack of basic utilities and medical care in the
      community. This resulted in the provision of an extensive public health outreach
      education program throughout the island. The Liberty and Manvel assessment
      findings suggest that most households in both communities were receiving the
      basic utilities and that the residents felt "safe". The assessments reassured
      local health officials that there were no substantial acute public health needs
      and provided objective information that services were being restored.

PMID- 21181684
TI  - Ambulance need at mass gatherings.
AB  - INTRODUCTION: Scant evidence exists to guide policy-making around public health
      needs during mass gatherings. In 2006, the City and County of San Francisco began
      requiring standby ambulances at all mass gatherings with attendance of >15,500
      people. The objectives were to evaluate needs for ambulances at mass gatherings,
      and to make evidence-based recommendations for public health policy-makers. The
      hypothesis was that the needs for ambulances at mass gatherings can be estimated
      using community baseline data. METHODS: Emergency medical services plans were
      reviewed for all public events with an anticipated attendance of >1,000 people in
      San Francisco County during the 12-month period 01 August 2006 through 31 July
      2007. Ambulance transport data were confirmed by event coordinators and ambulance
      company records, and the rate was calculated by dividing ambulance transports by
      event attendance. Baseline ambulance transport rate was calculated by dividing
      the annual ambulance transports in the county's computer-aided dispatch system by
      the census population estimate. The risk ratio was calculated using the risk of
      transport from a mass gathering compared with the baseline risk of ambulance
      transport for the local community. Significance testing and confidence intervals
      were calculated. RESULTS: Descriptive information was available for 100% of
      events and ambulance transport data available for 97% of events. The majority of
      the mass gatherings (47 unique events; 59 event days) were outdoor, weekend
      festivals, parades, or concerts, though a large proportion were athletic events.
      The ambulance transport rate from mass gatherings was 1 per 59,000 people every
      six hours. Baseline ambulance transport rate in San Francisco was 1 per 20,000
      people every six hours. The transport rate from mass gatherings was significantly
      lower than the community baseline (risk ratio [RR]=0.15, 95% CI=0.10-0.22,
      p<0.001). At events reserving a standby ambulance, 46% of ambulances were unused.
      DISCUSSION: San Francisco mass gatherings appear to present a lower risk of
      ambulance transports compared to the community baseline, suggesting that the
      community baseline sets an appropriate standard for requiring standby ambulances
      at mass gatherings. The initial ambulance requirement policy in San Francisco may
      have been overly conservative. CONCLUSIONS: Local baseline data is a recommended
      starting point when setting policy for public health needs at mass gatherings.

PMID- 21181685
TI  - Introduction of a prehospital critical incident monitoring system--final results.
AB  - BACKGROUND: Incident monitoring has been shown to improve patient care and has
      been adopted widely in the hospital care setting. There are limited data on
      incident monitoring in the prehospital setting. HYPOTHESIS: A high-yield, systems
      oriented, incident monitoring process can be implemented successfully in a
      prehospital setting. METHODS: This prospective, descriptive study outlines the
      implementation of an incident monitoring process in a regional prehospital
      setting. Both trauma care and non-trauma care were monitored by a system of
      anonymous reporting and chart review with debriefing for trauma cases that met
      major trauma criteria. A committee reviewed all identified cases and coded and
      logged all incidents and provider recommendations. RESULTS: There were 454
      incidents identified from 230 cases (mean=2.0; 95% CI 1.8-2.1 per case).
      Anonymous reporting resulted in the identification of 113 incidents from 69 cases
      (1.6l per case 95% CI=1.4-1.9 per case) Major trauma cases generated 266
      incidents from 134 cases (mean=2.0; 95% CI=1.8-2.2 per case), and there were 74
      incidents from 26 combined cases (mean=2.9; 95% CI=2.2-3.5 per case). One
      incident was uncategorized. There were 315 (69.4%) incidents categorized as
      management problems and 123 (27.1%) were system problems. Prolonged scene time
      was the most common incident in both management and system categories; 56 (17.8%)
      and 18 (14.6%) respectively. Mitigating circumstances were found in 111 (24.4%)
      incidents. The most common incident-related patient outcome was none/near miss
      (127 (28%)). Incident monitoring most commonly led to generalized feedback (105
      (23.1%)) or specific trend analysis (140 (30.8%)). Reports to higher or external
      bodies occurred in 18 incidents (4.0%). CONCLUSIONS: The project has been
      implemented successfully in a regional prehospital settling. The methodology,
      utilizing a number of incident detection techniques, results in a high yield of
      incidents over a broad range of error types. The large proportion of "near miss"
      type incidents allows for incident assessment without demonstrable patient harm.
      Many incidents were mitigated and the majority represented management-type
      issues.

PMID- 21181686
TI  - Out-of-hospital cardiac arrest-review of demographics in South Australia to
      inform decisions about the provision of automatic external defibrillators within
      the community.
AB  - INTRODUCTION: Sudden, out-of-hospital cardiac arrest (OHCA) has an annual
      incidence of approximately 50 per 100,000 population. Public access
      defibrillation is seen as one of the key strategies in the chain-of-survival for
      OHCA. Positioning of these devices is important for the maximization of public
      health outcomes. The literature strongly advocates widespread public access to
      automated external defibrillatiors (AEDs). The most efficient placement of AEDs
      within individual communities remains unclear. METHODS: A retrospective case
      review of OHCAs attended by the South Australia Ambulance Service in metropolitan
      and rural South Australia over a 30-month period was performed. Data were
      analyzed using Utstein-type indicators. Detailed demographics, summative data,
      and clinical data were recorded. RESULTS: A total of 1,305 cases of cardiac
      arrest were reviewed. The annual rate of OHCA was 35 per 100,000 population. Of
      the cases, the mean value for the ages was 66.3 years, 517 (39.6%) were
      transported to hospital, 761 (58.3%) were judged by the paramedic to be cardiac,
      and 838 (64.2%) were witnessed. Bystander cardiopulmonary resuscitation (CPR) was
      performed in 495 (37.9%) of cases. The rhythm on arrival was ventricular
      fibrillation (VF) or ventricular tachycardia (VT) in 419 (32.1%) cases, and 315
      (24.1%) of all arrests had return of spontaneous circulation (ROSC) before or on
      arrival at the hospital. For cardiac arrest cases that were witnessed by the
      ambulance service (n=121), the incidence of ROSC was 47.1%. During the 30-month
      period, there only was one location that recorded more than one cardiac arrest.
      No other location recorded recurrent episodes. CONCLUSIONS: This study did not
      identify any specific location that would justify defibrillator placement over
      any other location without an existing defibrillator. The impact of bystander CPR
      and the relatively low rate of bystander CPR in this study points to an area of
      need. The relative potential impact of increasing bystander CPR rates versus
      investing in defibrillators in the community is worthy of further consideration.

PMID- 21181687
TI  - Ability of First-Year Paramedic Students to Identify ST-Segment Elevation
      Myocardial Injury on 12-Lead Electrocardiogram: A Pilot Study.
AB  - INTRODUCTION: The purpose of this study was to evaluate the ability of firstyear
      paramedic students to identify ST-segment elevation myocardial injury (STEMI) on
      12-lead electrocardiograms (ECGs) following a three-hour presentation by a board
      certified emergency medicine physician experienced in ECG interpretation.
      METHODS: Thirty-three first-year paramedic students with minimal to no experience
      in evaluating 12-lead ECGs were administered a pre-test with 20 12-lead ECGs and
      were asked to evaluate each for: (1) presence of STEMI (STEMI identification);
      (2) if STEMI presents, ECG leads demonstrating ST-elevation (LEAD
      identification); and (3) if STEMI present, the anatomic distribution of the STEMI
      (ANATOMY identification). The students were randomized into two groups. Group 1
      (16 students; control group) received a handout describing the evaluation of ECGs
      for STEMI, while Group 2 (17 students; experimental group) received the handout
      plus a three hour presentation on the evaluation of ECGs for STEMI. Following
      randomization, distribution of the STEMI handout and ECG STEMI presentation, a
      post-test with 20 new ECGs was administered to all participants. The pretest and
      post-test mean scores were compared between the two groups to determine if
      attendance at the presentation improved the paramedic students' abilities to
      evaluate and identify STEMI ECGs. Following the STEMI posttest, students in Group
      1 were provided with the STEMI lecture. Students were retested with 20 new ECGs
      five months following the initial study to examine retention of the information
      taught. RESULTS: The mean pre-test scores for the two groups (Group 1 vs Group 2,
      respectively) in STEMI identification (74.4 vs 75.6%; p=0.79), lead
      identification (50.0 vs. 51.2%; p=0.8) and anatomy identification (49.4 vs 51.8%;
      p=0.60) were similar in all three categories. Post-test scores between Group 1
      and Group 2 demonstrated statistically significant differences in STEMI
      identification (85.6 vs 92.4%; p<0.02), lead identification (73.4 vs 85.2%;
      p<0.02), and anatomy identification (65.9 vs 87.1%; p<0.01), with Group 2
      demonstrating higher mean scores relative to Group 1 in all three categories.
      Comparison of mean initial pre-test and five-month retest scores for all students
      demonstrated statistically significant differences in STEMI identification (75.0
      vs 87.4%; p<0.0001), lead identification (50.6 vs 82.2%; p<0.0001), and anatomy
      identification (50.6 vs 76.6%; p<0.0001). CONCLUSIONS: The ability of first-year
      paramedic students to accurately detect STEMI on prehospital 12-lead ECGs is
      enhanced by a structured ECG STEMI presentation provided by an emergency medicine
      physician, and these students maintained excellent retention of STEMI ECG skills
      over a five-month period.

PMID- 21181688
TI  - Trained lay first responders reduce trauma mortality: a controlled study of rural
      trauma in Iraq.
AB  - INTRODUCTION: Recent studies demonstrate that early, in-field, basic life support
      by paramedics improves trauma survival where prehospital transport times are
      long. So far, no case-control studies of the effect of layperson trauma first
      responders have been reported. It was hypothesized that trained layperson first
      responders improve trauma outcomes where prehospital transit times are long.
      METHODS: A rural prehospital trauma system was established in the mine and war
      zones in Iraq, consisting of 135 paramedics and 7,000 layperson trauma first
      responders in the villages. In a non-randomized clinical study, the outcomes of
      patients initially managed in-field by first-responders were compared to patients
      not receiving first-responder support. RESULTS: The mortality rate was
      significantly lower among patients initially managed in-field by first responders
      (n=325) compared to patients without first-responder support (n=1,016), 9.8%;
      versus 15.6%;, 95%; CI=1.3-10.0%;. CONCLUSIONS: Trained layperson first
      responders improve trauma outcomes where prehospital evacuation times are long.
      This finding demonstrates that simple interventions done early-by any type of
      trained care provider-are crucial for trauma survival. Where the prevalence of
      severe trauma is high, trauma first-responders should be an integral element of
      the trauma system.

PMID- 21181689
TI  - Should trauma patients with a Glasgow Coma Scale score of 3 be intubated prior to
      hospital arrival?
AB  - INTRODUCTION: Previous studies of heterogeneous populations (Glasgow Coma Scale
      (GCS) scores<9) suggest that endotracheal intubation of trauma patients prior to
      hospital arrival (i.e., prehospital intubated) is associated with an increased
      mortality compared to those patients not intubated in the prehospital setting.
      Deeply comatose patients (GCS=3) represent a unique population of severely
      traumatized patients and may benefit from intubation in the prehospital setting.
      The objective of this study was to compare mortality rates of severely comatose
      patients (scene GCS=3) with prehospital endotracheal intubation to those
      intubated at the hospital. METHODS: Using the National Trauma Data Bank (V. 6.2),
      the following variables were analyzed retrospectively: (1) age; (2) injury type
      (blunt or penetrating); (3) Injury Severity Score (ISS); (4) scene GCS=3 (scored
      prior to intubation/without sedation); (5) emergency department GCS score; (6)
      arrival emergency department intubation status; (7) first systolic blood pressure
      in the emergency department (>0); (8) discharge status (alive or dead); (9)
      Abbreviated Injury Scale Score (AIS); and (10) AIS body region. RESULTS: Of the
      10,948 patients analyzed, 23% (2,491/10,948) were endotracheally intubated in a
      prehospital setting. Mortality rate for those hospital intubated was 35% vs. 62%
      for those with prehospital intubation (p<0.0001); mean ISS scores 24.2+/-16.0 vs.
      31.6+/-16.2, respectively (p<0.0001). Using logistic regression, controlling for
      first systolic blood pressure, ISS, emergency department GCS, age, and type of
      trauma, those with prehospital intubation were more likely to die (OR=1.9, 95%
      CI=1.7-2.2). For patients with only head AIS scores (no other body region injury,
      n=1,504), logistic regression (controlling for all other variables) indicated
      that those with prehospital intubation were still more likely to die (OR=2.0. 95%
      CI=1.4-2.9). CONCLUSIONS: Prehospital endotracheal intubation is associated with
      an increased mortality in completely comatose trauma patients (GCS = 3). Although
      the exact reasons for this remain unclear, these results support other studies
      and suggest the need for future research and re-appraisal of current policies for
      prehospital intubation in these severely traumatized patients.

PMID- 21181690
TI  - Development of a mass-gathering medical resource matrix for a developing world
      scenario.
AB  - Mass gatherings have a higher patient presentation rate than is found within the
      general population. Despite this fact, many mass gatherings are occurring without
      suitable medical coverage. South Africa has had no standard approach or model to
      determine the number of medical personnel needed to deploy to an event. The
      awarding of the FIFA (Federation International de Football Association) 2010
      World Cup to South Africa has provided the impetus for the development of such a
      model. The model presented in this paper is based on existing recommendations
      that originate from the United Kingdom. This paper outlines the modifications
      that have been made to this model to ensure that adequate medical resources still
      are provided, albeit in a developing country where medical resources may not be
      as plentiful.

PMID- 21181691
TI  - Editorial comments--Development of a mass-gathering medical resource matrix for a
      developing world scenario.

PMID- 21181692
TI  - Burn disasters--an audit of the literature.
AB  - All events that result in disasters are unique, and it is impossible to become
      fully prepared. However, through thorough planning and preparedness, it is
      possible to gain a better understanding of the typical injury patterns and
      problems that arise from a variety of hazards. Such events have the potential to
      claim many lives and overwhelm local medical resources. Burn disasters vary in
      scope of injury and procedures required, and are much more labor and resource
      intensive than non-burn disasters. This review of the literature should help
      determine whether, despite each event having its own unique features, there still
      are common problems disaster responders face in the prehospital and hospital
      phases, what recommendations were made from these disasters, and whether these
      recommendations have been implemented into practice and the current disaster
      planning processes. The objective of this review was to assess: (1) prehospital
      and hospital responses used during past burn disasters; (2) problems faced during
      those disaster responses; (3) recommendations made following those disasters; (4)
      whether these recommendations were integrated into practice; and (5) the key
      characteristics of burn disasters and how they differ from other disasters. This
      review is important to determine why, despite having disaster plans, things still
      go wrong.

PMID- 21181694
TI  - Editorial comments: Burn disasters--an audit of the literature.

PMID- 21181693
TI  - Editorial comments: Burn disasters--an audit of the literature.

PMID- 21181695
TI  - QuikClot Combat Gauze use for hemorrhage control in military trauma: January 2009
      Israel Defense Force experience in the Gaza Strip--a preliminary report of 14
      cases.
AB  - BACKGROUND: Standard gauze field dressings and direct pressure occasionally are
      inadequate for the control of hemorrhage. QuikClot(r) Combat GauzeTM (QCG)
      combines surgical gauze with an inorganic material and is approved by the Food
      and Drug Administration and by the Israeli Standards Institute for external
      hemorrhage control. The purpose of this article is to report clinical use of this
      dressing during Operation Cast Lead in the Gaza strip during January 2009.
      METHODS: QuikClot Combat Gauze and the QCG guidelines were issued to advanced
      life support (ALS) providers during the preparations for the Operation. All cases
      of injuries involving hemorrhage were reviewed, as well as interviews with the
      ALS providers (physicians and paramedics) and injured soldiers. RESULTS: Fourteen
      uses of QCG were reported and reviewed (out of a total of 56 hemostatic
      interventions in 35 cases). Dressings were applied to injuries to the head, neck,
      axilla, buttocks, abdomen, back, and pelvis in 10 cases, and to extremities in
      four cases. In 13 cases (93%), injuries were caused by blast or gunshot
      mechanisms. The success rate was reported as 79% (11/14). Failure to control
      hemorrhage was reported in three cases in three different locations: neck,
      buttock, and thigh. All failures were attributed to severe soft tissue and
      vascular injuries. No complications or adverse events were reported. CONCLUSIONS:
      This report on the clinical field use of the QCG dressing by ALS providers
      suggests that it is an effective and safe product, and applicable for prehospital
      treatment of combat casualties. This report further suggests that QCG should be
      issued to medics as well as ALS providers. Larger clinical investigations are
      needed to confirm these findings.

PMID- 21181696
TI  - Comparison of techniques for securing the endotracheal tube while wearing
      chemical, biological, radiological, or nuclear protection: a manikin study.
AB  - OBJECTIVE: The objective of this study was to assess the impact of chemical,
      biological, radiological, nuclear personal protective equipment (CBRN-PPE) on the
      ability to secure an endotracheal tube (ETT) with either the Thomas Tube HolderTM
      or cotton tape tied in a knot. METHODS: Seventy-five clinicians secured an ETT in
      a previously intubated manikin with the Thomas Tube HolderTM and cotton tape. A
      mixed quantitative and qualitative research design was used to gauge actual
      performance times and perceptions of difficulties. Following completion of the
      study, 25 clinicians were interviewed to gauge their experiences of securing the
      ETT with both devices while wearing CBRN-PPE. RESULTS: The mean time to apply the
      Thomas Tube Holder was 29.02 seconds, compared with tape which took a mean of 58
      seconds (p=0.001). Clinicians rated the Thomas Tube Holder as easier to use than
      tape (Mann-Whitney z=9.934; p<0.001), which was confirmed during interviews. Of
      the clinicians interviewed, 92% perceived that the Thomas Tube Holder provided
      the better method for securing an ETT, none of the clinicians identified the tape
      as the best method for securing the endotracheal tube while wearing CBRN-PPE.
      Clinicians identified that the design of the Thomas Tube Holder facilitated the
      gross motor movement required for application. CONCLUSIONS: The Thomas Tube
      Holder is easier and faster to apply when wearing CBRN-PPE when compared with
      cotton, and the Thomas Tube Holder is perceived by the participants as being more
      effective at preventing accidential extubation.

PMID- 21181697
TI  - Prehospital care algorithm for blast injuries due to bombing incidents.
AB  - Terrorist bombings continue to remain a risk for local jurisdictions, and
      retrospective data from the United States show that bombings occur in residential
      and business areas due to interpersonal violence without political motives. In
      the event of a mass-casualty bombing incident, prehospital care providers will
      have the responsibility for identifying and managing blast injuries unique to
      bombing victims. In a large-scale event, emergency medical services personnel
      should be required to provide prolonged medical care in the prehospital setting,
      and they will be able to deliver improved care with a better understanding of
      blast injuries and a concise algorithm for managing them. Blast injuries are
      categorized as primary, secondary, tertiary, and quaternary, and these injuries
      are related to the mechanism of injury from the blast event. After an initial
      evaluation, the emergency healthcare provider should consider following a
      universal algorithm to identify and treat blast injuries within these categories
      to prevent further morbidity or mortality in the prehospital setting.

PMID- 21181698
TI  - Editorial comments--Prehospital care algorithm for blast injuries due to bombing
      incidents.

PMID- 21181699
TI  - Re: Where there are no emergency medical services--prehospital care for the
      injured in Mumbai, India.

PMID- 21181700
TI  - Re: Haiti disaster tourism--a medical shame.

PMID- 21181701
TI  - Re: Regulating the helping hand: improving legal preparedness for cross-border
      disaster medicine.

PMID- 21181702
TI  - Re: Estimating blood transfusion requirements in preparation for a major
      earthquake: the Tehran, Iran study.

PMID- 21181703
TI  - Authentication of the 31 species of toxic and potent Chinese materia medica by
      microscopic technique assisted by ICP-MS analysis, part 4: four kinds of toxic
      and potent mineral arsenical CMMs.
AB  - Toxic and Potent Chinese Materia Medica (T/PCMM) is a special and very important
      category of Chinese medicines. They have long been used in traditional medical
      practice and are being used more and more widely throughout the world in recent
      years. As there may be many fatal toxic effects caused by misusing or confusion
      of T/PCMM, their quality and safety control arouse increasing attention
      internationally. Researches on the accurate identification to ensure the safe use
      of T/PCMM are acquired; however, there are few reports on authentication. We are
      carrying out a series of studies on 31 T/PCMM originating from plants, animals,
      minerals, and secreta. In our previous studies, we proved that modern microscopic
      authentication is a simple, fast, effective, low cost, and less toxic method for
      identifying animal, seed, and flower T/PCMM. In the present study, we focused on
      the authentication of four kinds of mineral arsenicals, including orpiment
      (mainly containing As2S3), realgar (mainly containing As4S4), arsenolite, and
      arsenic trioxide (mainly containing As2O3). We examined the macroscopic and
      microscopic characteristics of the above minerals and found that they all can be
      easily identified and authenticated by using light microscopy coupled with
      polarized microscopy. Moreover, the authentication results for arsenolite and
      arsenic trioxide are confirmed by ICP-MS analysis. We are sure that the
      morphological and microscopic characteristics indicated here are indispensable to
      establishing standards for these four mineral T/PCMMs.

PMID- 21181704
TI  - Multiphoton fluorescence lifetime imaging of 3D-stem cell spheroids during
      differentiation.
AB  - Long-term high-resolution multiphoton imaging of nonlabeled human salivary gland
      stem cell spheroids has been performed with submicron spatial resolution, 10.5-nm
      spectral resolution, and picosecond temporal resolution. In particular, the two
      photon-excited coenzyme NAD(P)H and flavins have been detected by time-correlated
      single photon counting (TCSPC). Stem cells increased their autofluorescence
      lifetimes and decreased their total fluorescence intensity during the adipogenic
      differentiation process. In addition, the onset of the biosynthesis of lipid
      vacuoles was monitored over a period of several weeks in stem-cell spheroids.
      Time-resolved multiphoton autofluorescence imaging microscopes may become a
      promising tool for marker-free stem-cell characterization and cell sorting.

PMID- 21181705
TI  - Application of WGA lectin staining for visualization of the connective tissue in
      skeletal muscle, bone, and ligament/tendon studies.
AB  - During immunostaining of specific proteins in tissue sections using monoclonal
      and polyclonal antibodies, visualization of general tissue staining/background or
      major structural features is helpful to pinpoint precise localization of the
      protein of interest. Often in skeletal muscle research, immunostaining with
      antibodies against connective tissue or plasma membrane proteins (collagen 1,
      laminin, and caveolin 3) are used for this purpose. Although immunostaining for
      these proteins works well, it is time consuming, costly, limits the number of
      antibodies against protein of interest that can be used on a single section, and
      is not applicable to some staining techniques. Lectins were frequently used in
      earlier publications for skeletal muscle fiber boundaries and connective tissue
      visualization, but are not common in the current research studies. This work
      investigates costaining of muscle, bone, ligament, and tendon tissue sections
      with fluorescently tagged wheat germ agglutinin (WGA) lectin as a tool for the
      visualization of connective tissue. The results of this study show that
      fluorescent WGA lectin costaining is a cost-effective, fast, and convenient
      method for connective tissue visualization, especially in the studies where
      extensive washes reduce staining of the structures that are the primary interest
      of the investigation.

PMID- 21181706
TI  - Nanohybrid versus nanofill composite in class I cavities: margin analysis after
      12 months.
AB  - This study evaluates the margin of a nanofill, a nanohybrid, and a conventional
      microhybrid composite in restorations in occlusal cavities of posterior teeth
      after 12 months. Forty-one patients, each with three molars affected by primary
      caries or the need to replace restorations, participated in this research. The
      teeth were restored with a nanofill (Filtek Z350), a nanohybrid (Esthet-X), and a
      microhybrid as a control (Filtek Z250). Ten patients were selected randomly, and
      the three restorations were molded with a low-viscosity polyvinyl siloxane
      material. The molds were poured with epoxy resin, gold-sputter coated, observed
      by scanning electron microscopy, and classified as: "perfect margin," "marginal
      irregularity," "marginal gap," "marginal fracture," or "artifact." For
      statistical analysis, the Wilcoxon and Friedman nonparametric tests and paired
      samples t-test were used (significance level of 5%). The performance of the three
      materials was compared after 1 week and 12 months. No statistically significant
      differences were detected for all criteria (P > 0.05). When each composite was
      compared over time, statistically significant differences were found for the
      criterion, perfect margins (Esthet-X and Filtek Z350, P < 0.05). The materials
      performed satisfactorily over the 12-month-observation period, but all composites
      under investigation showed a certain amount of deterioration relating to marginal
      quality over time.

PMID- 21181707
TI  - UV-reflecting wing scales in the silk moth Antheraea assamensis: its biophysical
      implications.
AB  - Scanning electron microcopy of the wing scales from some specific locations in
      the silk moth, Antheraea assamensis, revealed the presence of 50-60-nm-thick
      microridges and 80-nm-thick air spaces between them. The principle of optics
      suggests that when the measured average thickness of microridges or lamellae is
      about 50-60 nm, that of the air-space between them is about 80-82 nm, then due to
      the known refractive index of air (1.0) and the infrared refractive index of
      lamellar cuticle (1.60), the lamellae (microridges) and the intervening lamellar
      air spaces will have similar optical thickness. A common optical thickness for
      the two types of layers causes the microridge structures to function in the
      fashion of a quarter wavelength interference filter and to reflect UV light.
      Behavioral studies under the natural conditions and short experimental exposure
      of the moths to artificial UV light suggests that coupling behavior of the moth
      is governed to a significant extent by these UV-reflecting wing scales. The
      importance of the study in overcoming a major problem of low autocoupling
      efficiency of moths in the Muga Silk Industry is discussed with the help of
      relevant literature.

PMID- 21181708
TI  - Automatic evaluation of nickel alloy secondary phases from SEM images.
AB  - Quantitative metallography is a technique to determine and correlate the
      microstructures of materials with their properties and behavior. Generic
      commercial image processing and analysis software packages have been used to
      quantify material phases from metallographic images. However, these all-purpose
      solutions also have some drawbacks, particularly when applied to segmentation of
      material phases. To overcome such limitations, this work presents a new solution
      to automatically segment and quantify material phases from SEM metallographic
      images. The solution is based on a neuronal network and in this work was used to
      identify the secondary phase precipitated in the gamma matrix of a Nickel base
      alloy. The results obtained by the new solution were validated by visual
      inspection and compared with the ones obtained by a commonly used commercial
      software. The conclusion is that the new solution is precise, reliable and more
      accurate and faster than the commercial software.

PMID- 21181709
TI  - Immunoelectron microscopic characterization of nucleolus-associated domains
      during hibernation.
AB  - The nucleolus represents a highly dynamic nuclear compartment involved in
      multiple functions and able to promptly respond to variations of metabolic needs.
      In the hibernator dormouse, which drastically modifies its metabolic activity
      during the seasonal cycle, the nucleolus undergoes structural and molecular
      changes during the torpor bouts; in particular, it shows many nucleoplasmic
      invaginations containing weakly contrasted areas of unknown nature. To analyze
      the molecular composition of these nucleolus-associated domains (NADs) and to
      understand their functional significance, the fine nucleolar composition has been
      investigated by means of ultrastructural immunocytochemistry in different tissues
      of euthermic, hibernating, and arousing hazel dormice (Muscardinus avellanarius):
      in particular, the intranucleolar location of several protein factors involved in
      the transcription and processing of either pre-rRNA or pre-mRNA has been
      considered. NADs proved to form during hibernation and disappear upon arousal and
      were found to contain m3-G-capped snRNAs, snRNPs, hnRNPs, and the survival motor
      neuron protein; they were, on the contrary, devoid of the nucleolar factors
      tested (polymerase I, fibrillarin, nucleolin, and the ribosomal phosphoproteins
      P0, P1, and P2). We hypothesize that NADs may represent a transient storage site
      for those molecules involved in the pre-mRNA splicing, which usually transit
      through the nucleolus; upon arousal, this would facilitate the resumption of RNA
      maturation by promoting the rapid reactivation of the molecular trafficking from
      the nucleolus.

PMID- 21181710
TI  - Effect of ultrasonic excitation on the porosity of glass ionomer cement: a
      scanning electron microscope evaluation.
AB  - BACKGROUND: Ultrasonic excitation (US) was applied to glass ionomer cement (GIC)
      during early set time to increase the advantageous properties of this material.
      PURPOSE: The aim of this in vitro study was to assess the inner porosity of GIC
      after US. STUDY DESIGN: A total of 16 specimens, for each material, were prepared
      from high-viscosity GIC Fuji IX GP, Ketac Molar, and Ketac Molar Easymix. Half of
      these specimens (n = 8) received 30 s of US during the initial cement setting.
      After completion of the material setting, specimens were fractured and observed
      by scanning electronic microscopy to quantitatively assay porosity inside the
      material using Image J software. RESULTS: Statistical data analysis revealed that
      US reduced the porosity for all tested materials (P <= 0.05). The following
      reductions (expressed in percentages) were achieved: Fuji IX--from 3.9% to 2.8%;
      Ketac Molar Easy Mix--from 4.4% to 2.6%, and Ketac Molar--from 2.4% to 1.6%.
      CONCLUSION: Under the tested conditions, US was an effective method for porosity
      reduction inside the material.

PMID- 21181711
TI  - Texture analysis of TEM micrographs of alginate gels for cell microencapsulation.
AB  - In this work, the morphological characteristics of a calcium alginate gel and a
      binary (gel) mixture composed of (calcium) alginate and lactose-modified chitosan
      (chitlac) are evaluated and compared to quantify the differences between the two
      three-dimensional (3D) structures. A set of textural descriptors based on
      histogram analysis as well as on gray level co-occurrence matrix and on fractal
      dimension is extracted from transmission electron microscopy micrographs to
      describe the morphological differences that the images present. The obtained
      results reveal significant quantitative morphological differences between the
      calcium alginate gel and the binary gel mixture that were already inferred from
      rheological experiments, so as to provide a structural basis for developing new
      encapsulation systems based on such mixed polymer gels.

PMID- 21181712
TI  - Microvasculature of the buffalo (Bubalus bubalis) choroid plexuses: structural,
      histochemical, and immunocytochemical study.
AB  - The choroid plexuses (CPs) in mammals produce the cerebrospinal fluid (CSF). In
      the literature, the morphology of CPs and the process that regulates the
      production of CSF are virtually nonexistent for domestic ruminants. Thus this
      study has two aims: 1. to investigate the morpho-structure of the buffalo CP
      microvasculature utilizing light microscopy (LM), scanning electron microscopy
      (SEM) and transmission electron microscopy (TEM) techniques, and 2. to
      investigate the relationship between the blood vessels and both the elongated
      cells and the cells with multiple protrusions located in the CPs. SEM and TEM
      analyses of the CPs from buffalo brain showed morphological and structural
      features similar those reported in other mammalian species. Moreover the blood
      microvasculature is the major component responsible for the formation of the CSF,
      secreted by the encephalic CPs. In addition the chemical composition of this
      fluid depends on several morpho-functional characteristics of the vascularization
      of the CPs. These characteristics are as follows: two shapes of the vascular
      organization: lamina-like and ovoid-like elongated cells of the CPs, which
      connect the ventricular cavities to the blood capillaries; and the CP capillaries
      have diverse forms. In the present study the employment of NADPHd and NOS I was
      taken as indirect evidence for the presence of NO for investigation their
      specific role in CPs. Then NOS I immunoreactivity is found in the walls of CP
      blood vessels demonstrating indirectly the presence of NO with a vaso-dilatatory
      and autoregulation function of vascular tone by cholinergic nerve stimulation of
      blood vessel smooth muscle.

PMID- 21181713
TI  - Secretory profile of metapleural gland cells of the leaf-cutting ant Acromyrmex
      coronatus (Formicidae: Attini).
AB  - Ants present a pair of metapleural glands located at the posterolateral end of
      the thorax. Because of its importance in the social organization of ants, the
      present study was aimed at describing the morphophysiology of this gland in three
      worker castes of Acromyrmex coronatus, focused on secretory activity using
      histological and histochemical techniques. Our findings revealed that the
      secretory and the storage portions of this gland are connected by
      extracytoplasmic portion of canaliculi that drain the secretion from each
      secretory cell to the collecting chamber. This secretion contains glycoproteins.
      In minor workers, the secretion contains higher levels of polysaccharides when
      compared to that of major workers, supporting the role of the metapleural gland
      in the maintenance of the fungus garden. The nucleus as well as cytoplasm of
      secretory cells were strongly positive for RNA indicating that these cells are
      active in the synthesis of proteins and lipids, compounds found in the final
      secretion. The variant of the CEC revealed that the secretory activity of the
      entire gland is synchronous, as all cells exhibit the result.

PMID- 21181714
TI  - Reducing the formation of FIB-induced FCC layers on Cu-Zn-Al austenite.
AB  - The irradiation effects of thinning a sample of a Cu-Zn-Al shape memory alloy to
      electron transparency by a Ga(+) focused ion beam were investigated. This
      thinning method was compared with conventional electropolishing and Ar(+) ion
      milling. No implanted Ga was detected but surface FCC precipitation was found as
      a result of the focused ion beam sample preparation. Decreasing the irradiation
      dose by lowering the energy and current of the Ga(+) ions did not lead to a
      complete disappearance of the FCC structure. The latter could only be removed
      after gentle Ar(+) ion milling of the sample. It was further concluded that the
      precipitation of the FCC is independent of the crystallographic orientation of
      the surface.

PMID- 21181715
TI  - Potential of ultraviolet wide-field imaging and multiphoton microscopy for
      analysis of dehydroergosterol in cellular membranes.
AB  - Dehydroergosterol (DHE) is an intrinsically fluorescent sterol with
      absorption/emission in the ultraviolet (UV) region and biophysical properties
      similar to those of cholesterol. We compared the potential of UV-sensitive low
      light-level wide-field (UV-WF) imaging with that of multiphoton (MP) excitation
      microscopy to monitor DHE in living cells. Significantly reduced photobleaching
      in MP microscopy of DHE enabled us to acquire three-dimensional z-stacks of DHE
      stained cells and to obtain high-resolution maps of DHE in surface ruffles,
      nanotubes, and the apical membrane of epithelial cells. We found that the lateral
      resolution of MP microscopy is ~1.5-fold higher than that of UV-WF deconvolution
      microscopy, allowing for improved spatiotemporal analysis of plasma membrane
      sterol distribution. Surface intensity patterns of DHE with a diameter of 0.2 MUm
      persisting over several minutes could be resolved by MP time-lapse microscopy.
      Diffusion coefficients of 0.25-MUm-diameter endocytic vesicles containing DHE
      were determined by MP spatiotemporal image correlation spectroscopy. The
      requirement of extremely high laser power for visualization of DHE by MP
      microscopy made this method less potent for multicolor applications with
      organelle markers like green fluorescent protein-tagged proteins. The signal-to
      noise ratio obtainable by UV-WF imaging could be significantly improved by
      pixelwise bleach rate fitting and calculation of an amplitude image from the
      decay model and by frame averaging after pixelwise bleaching correction of the
      image stacks. We conclude that UV-WF imaging and MP microscopy of DHE provide
      complementary information regarding membrane distribution and intracellular
      targeting of sterols.

PMID- 21181716
TI  - SEM evaluation of thermoplastic endodontic materials alterations after
      disinfection: a new experimental model.
AB  - This study assessed a new experimental model to analyze the effects of sodium
      hypochlorite solution 2.5% for 10 min and chlorhexidine 2% for 15 s on cones
      surface alterations. Twenty five gutta-percha and 25 thermoplastic synthetic
      polymer-based cones had their last 1 mm from the tapered end examined by scanning
      electron microscopy (SEM) before and after being exposed to the disinfectant
      solutions. To allow the surfaces to be compared, the samples were not metalized,
      a voltage of 1 kV was used and the images were captured within standardized
      angles. The samples were immersed on the test solutions. The comparison of the
      alterations of the cones was performed using the software program Adobe Photoshop
      CS. A measurement was taken of the standard deviations of the pixel intensity in
      this area, higher standard deviations represent more irregular areas. Differences
      in standard deviation before and after disinfection for each cone were compared
      between groups by means of analysis of variance supplemented by the Tukey test.
      Gutta-percha cones showed higher standard deviations than Resilon cones (P <
      0.001). In the gutta-percha cones, sodium hypochlorite generated more irregular
      areas than chlorhexidine and the control group (P < 0.001). The present study has
      demonstrated the feasibility of using a modified SEM method. This opens
      opportunities to the use of new and precise tools for evaluating a sample in
      different moments.

PMID- 21181717
TI  - Increased brain atrophy rates in cognitively normal older adults with low
      cerebrospinal fluid Abeta1-42.
AB  - OBJECTIVE: To identify cognitively normal individuals at risk of Alzheimer
      disease (AD) based on cerebrospinal fluid (CSF) Abeta1-42, and to determine rates
      of cerebral atrophy. METHODS: Control subjects from the Alzheimer's Disease
      Neuroimaging Initiative with CSF and serial magnetic resonance imaging (MRI) were
      dichotomized on CSF Abeta1-42 (normal control [NC]-high > 192 pg/ml; NC-low <=
      192 pg/ml). Baseline and 1-year MRIs were registered, and brain, hippocampal, and
      ventricular volumes and annualized volume changes were calculated. Baseline
      characteristics, CSF profiles, neuropsychology, brain volumes and atrophy rates,
      and APOE, PICALM, CLU, and TOMM40 genotypes were compared. Sample sizes to power
      presymptomatic clinical trials based on rate of atrophy were calculated. RESULTS:
      Forty of 105 (38%) were classified as NC-low, and 65 (62%) as NC-high. There were
      no differences in age (76.3 +/- 5.1 vs 74.9 +/- 5.1 years), gender, brain
      volumes, and all but 1 cognitive score (Trails B; p = 0.015). The NC-low group
      had higher tau (p = 0.005) and p-tau (p < 0.001), and was more likely to be APOE4
      positive (48% vs 11%, p < 0.001). The NC-low group had significantly higher whole
      brain loss (9.3 vs 4.4 ml/yr, p < 0.001), ventricular expansion (2.04 vs 0.95
      ml/yr, p = 0.002), and hippocampal atrophy rate (0.07 vs 0.03 ml/yr, p = 0.029).
      Baseline Abeta1-42 level was strongly correlated with rate of brain atrophy only
      in the NC-low group (p < 0.001). Using 141 (95% confidence interval, 86-287)
      patients per arm provides 80% power in a 1-year treatment trial to show 25%
      slowing of brain atrophy in the NC-low group. INTERPRETATION: A significant
      percentage of healthy older adults have CSF profiles consistent with AD and
      increased rates of brain atrophy, suggesting that they may be in the earliest
      stages of neurodegeneration. Brain atrophy may be a feasible outcome measure for
      AD prevention studies.

PMID- 21181719
TI  - The mechanism of papain inhibition by peptidyl aldehydes.
AB  - Various mechanisms for the reversible formation of a covalent tetrahedral complex
      (TC) between papain and peptidyl aldehyde inhibitors were simulated by DFT
      calculations, applying the quantum mechanical/self consistent reaction field
      (virtual solvent) [QM/SCRF(VS)] approach. Only one mechanism correlates with the
      experimental kinetic data. The His-Cys catalytic diad is in an N/SH protonation
      state in the noncovalent papain-aldehyde Michaelis complex. His159 functions as a
      general base catalyst, abstracting a proton from the Cys25, whereas the activated
      thiolate synchronously attacks the inhibitor's carbonyl group. The final product
      of papain inhibition is the protonated neutral form of the hemithioacetal TC(OH),
      in agreement with experimental data. The predicted activation barrier g enz? =
      5.2 kcal mol-1 is close to the experimental value of 6.9 kcal mol-1. An
      interpretation of the experimentally observed slow binding effect for peptidyl
      aldehyde inhibitors is presented. The calculated g cat? is much lower than the
      rate determining activation barrier of hemithioacetal formation in water, g w?,
      in agreement with the concept that the preorganized electrostatic environment in
      the enzyme active site is the driving force of enzyme catalysis. We have
      rationalized the origin of the acidic and basic pK(a)'s on the k2/K(S) versus pH
      bell-shaped profile of papain inhibition by peptidyl aldehydes.

PMID- 21181760
TI  - Genetic influences on surgical oncology.

PMID- 21181720
TI  - An epidermis-specific chitin synthase CDNA in Choristoneura fumiferana: cloning,
      characterization, developmental and hormonal-regulated expression.
AB  - Chitin synthase catalyzes chitin synthesis in the exoskeleton, tracheal system
      and gut during insect development. A chitin synthase 1 (CfCHS1) cDNA was
      identified and cloned from the spruce budworm, Choristoneura fumiferana. The
      CfCHS1 cDNA is 5,300 bp in length and codes a 1,564-amino acid protein with a
      molecular mass of 178 kDa. The deduced protein contains 16 transmembrane helixes
      in its domains A and C. The single copy CfCHS1 gene expressed during each of the
      larval molts from the 3rd to the 6th instar. The gene expressed highly and
      periodically in the epidermis during each of molts, whereas no transcripts were
      detected in the midgut and fat body. 20-hydroxyecdysone and the ecdysone agonist
      RH5992 suppressed CfCHS1 expression, whereas the juvenile hormone analog
      methoprene induced CfCHS1 expression. These results implicate that CfCHS1 is
      involved in the chitin synthase and new chitin formation during molting in the
      insect.

PMID- 21181766
TI  - Self-assembled DNA hydrogels with designable thermal and enzymatic
      responsiveness.

PMID- 21181768
TI  - Evaluation of charge mobility in organic materials: from localized to delocalized
      descriptions at a first-principles level.
AB  - The carrier mobility for carbon electronic materials is an important parameter
      for optoelectronics. We report here some recently developed theoretical tools to
      predict the mobility without any free parameters. Carrier scatterings with
      phonons and traps are the key factors in evaluating the mobility. We consider
      three major scattering regimes: i) where the molecular internal vibration
      severely induces charge self-trapping and, thus, the hopping mechanism dominates;
      ii) where both intermolecular and intramolecular scatterings come to play roles,
      so the Holstein-Peierls polaron model is applied; and, iii) where charge is well
      delocalized with coherence length comparable with acoustic phonon wavelength, so
      that a deformation potential approach is more appropriate. We develop
      computational methods at the first-principles level for the three different cases
      that have extensive potential application in rationalizing material design.

PMID- 21181769
TI  - Strategies for post-synthesis alignment and immobilization of carbon nanotubes.
AB  - Carbon nanotubes (CNTs) have developed into a standard material used as a
      building block for nanotechnological developments. Based on the unique properties
      that make CNTs useful for many different applications in nanotechnology, optics,
      electronics, and material science, there has been a rapid development of this
      research area and many different applications have emerged in the past few years.
      Frequently, the alignment and immobilization of CNTs play an important role for
      many applications and different strategies, in particular post-synthesis
      approaches, can be applied. Recent developments of different techniques to
      immobilize and align carbon nanotubes are discussed and classified into three
      main categories: chemical immobilization and alignment, physical immobilization
      and alignment, and the use of external fields for these purposes. Many of the
      techniques involve multiple steps and may also cross these rather crudely defined
      boundaries. As such, the techniques are classified according to their most
      important or unique step.

PMID- 21181781
TI  - Isolation and expression analysis of a homolog of the 14-3-3 epsilon gene in the
      diamondback moth, Plutella xylostella.
AB  - A full-length 14-3-3 gene homolog (also referred to as the Px14-3-3 epsilon
      "epsilon" or Px14-3-3epsilon gene) was cloned from cDNA of the diamondback moth,
      Plutella xylostella. The Px14-3-3 transcript is 789 nucleotides in length, and
      the predicted polypeptide is 263 amino acids in length, with a calculated
      molecular mass of 29.6 kDa. The Px14-3-3 gene contains the typical and predicted
      14-3-3 domains and motifs. The amino acid sequence of the diamondback moth 14-3-3
      gene is very similar to that of other insect epsilons (epsilon) but not to other
      insect zetas (zeta). In particular, the protein sequence of the Px14-3-3 gene
      shows high identity to the Bombyx mori epsilon (96.2%). Western blot analysis
      using an antibody against Px14-3-3epsilon verified the expression of 14-3
      3epsilon in the larval, pupal, and adult stages. The Px14-3-3epsilon expression
      patterns in all the different tissue types were examined in the fourth instar
      larvae. Px14-3-3epsilon was detected in every tissue examined, including the body
      fat, hemocytes, brain, gut, and cuticle.

PMID- 21181784
TI  - Challenges in measuring the delta13C of the soil surface CO2 efflux.
AB  - The delta13C of the soil surface efflux of carbon dioxide (delta13CRS) has
      emerged as a powerful tool enabling investigation of a wide range of soil
      processes from characterising entire ecosystem respiration to detailed compound
      specific isotope studies. delta13CRS can be used to trace assimilated carbon
      transfer below ground and to partition the overall surface efflux into
      heterotrophic and autotrophic components. Despite this wide range of applications
      no consensus currently exists on the most appropriate method of sampling this
      surface efflux of CO2 in order to measure delta13CRS. Here we consider and
      compare the methods which have been used, and examine the pitfalls. We also
      consider a number of analysis options, isotope ratio mass spectrometry (IRMS),
      tuneable diode laser spectroscopy (TDLS) and cavity ring-down laser spectroscopy
      (CRDS). delta13CRS is typically measured using chamber systems, which fall into
      three types: closed, open and dynamic. All are imperfect. Closed chambers often
      rely on Keeling plots to estimate delta13CRS, which may not be appropriate
      without free turbulent air mixing. Open chambers have the advantage of being able
      to maintain steady-state conditions but analytical errors may become limiting
      with low efflux rates. Dynamic chambers like open chambers are complex, and
      controlling pressure fluctuations caused by air movement is a key concern. Both
      open and dynamic chambers in conjunction with field portable TDLS and CRDS
      analysis systems have opened up the possibility of measuring delta13CRS in real
      time permitting new research opportunities and are on balance the most suited to
      this type of measurement.

PMID- 21181786
TI  - Exploring the after-effects of theta burst magnetic stimulation on the human
      motor cortex: a functional imaging study.
AB  - Theta burst stimulation (TBS) is a protocol of subthreshold repetitive
      transcranial magnetic stimulation (rTMS) inducing changes in cortical
      excitability. From functional imaging studies with conventional subthreshold rTMS
      protocols, it remains unclear what type of modulation occurs (direction and
      dependency to neural activity) and whether putative effects are bound to
      unspecific changes in cerebral perfusion or require a functional challenge. In a
      within-subjects (n = 17) repeated measurement design including real TBS and a
      control session without stimulation, we examined neural activation in a choice
      reaction task after application of intermittent TBS, a protocol, which enhances
      cortical excitability over the left motor cortex (M1). Brain activity was
      monitored by blood oxygenation level-dependent (BOLD) functional magnetic
      resonance imaging interleaved with measuring regional cerebral blood flow (rCBF)
      at rest using MR-based perfusion imaging. On a separate day, TMS-induced compound
      muscle action potentials (cMAPs) amplitude of the right hand was measured after
      excitatory TBS. Compared to control, a significant decrease in BOLD signal due to
      right hand motor activity during the choice-reaction task was observed mainly in
      the stimulated M1 and motor-related remote areas after stimulation. This decrease
      might represent a facilitating effect, because cMAPs amplitude increased upon TBS
      compared to control. No changes in rCBF at rest were observed. The data
      demonstrate that subthreshold intermittent TBS targets both the stimulated
      cortical area as well as remote areas. The facilitation changing the efficacy of
      neural signal transmission seems to be reflected by a BOLD signal decrease,
      whereas the network at rest does not appear to be affected.

PMID- 21181798
TI  - Stability of clinical condition in mild cognitive impairment is related to
      cortical sources of alpha rhythms: an electroencephalographic study.
AB  - Previous evidence has shown that resting eyes-closed cortical alpha rhythms are
      higher in amplitude in mild cognitive impairment (MCI) than Alzheimer's disease
      (AD) subjects (Babiloni et al. [2006a]: Human Brain Mapp 27:162-172; [2006b]:
      Clin Neurophysiol 117:252-268; [2006c]: Neuroimage 29:948-964; [2006d]: Ann
      Neurol 59:323-334; [2006e]: Clin Neurophysiol 117:1113-1129; [2006f]: Neuroimage
      31:1650-1665). This study tested the hypothesis that, in amnesic MCI subjects,
      high amplitude of baseline cortical alpha rhythms is related to long-term
      stability of global cognition on clinical follow-up. Resting
      electroencephalographic (EEG) data were recorded in 100 amnesic MCI subjects
      during eyes-closed condition. EEG rhythms of interest were delta (2-4 Hz), theta
      (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), and beta2
      (20-30 Hz). Cortical EEG sources were estimated by low-resolution brain
      electromagnetic tomography (LORETA). Global cognition was indexed by mini mental
      state evaluation (MMSE) score at the time of EEG recordings (baseline) and about
      after 1 year. Based on the MMSE percentage difference between baseline and 1-year
      follow-up (MMSEvar), the MCI subjects were retrospectively divided into three
      arbitrary groups: DECREASED (MMSEvar <= -4%; N = 43), STABLE (MMSEvar ~ 0; N =
      27), and INCREASED (MMSEvar >= +4%; N = 30). Subjects' age, education, individual
      alpha frequency, gender, and MMSE scores were used as covariates for statistical
      analysis. Baseline posterior cortical sources of alpha 1 rhythms were higher in
      amplitude in the STABLE than in the DECREASED and INCREASED groups. These results
      suggest that preserved resting cortical neural synchronization at alpha frequency
      is related to a long-term (1 year) stable cognitive function in MCI subjects.
      Future studies should use serial MMSE measurements to confirm and refine the
      present results.

PMID- 21181799
TI  - Clinical functional MRI of the language domain in children with epilepsy.
AB  - Functional MRI (fMRI) for the assessment of language functions is increasingly
      used in the diagnostic workup of patients with epilepsy. Termed "clinical fMRI,"
      such an approach is also feasible in children who may display specific patterns
      of language reorganization. This study was aimed at assessing language
      reorganization in pediatric epilepsy patients, using fMRI. We studied 26
      pediatric epilepsy patients (median age, 13.05 years; range, 5.6-18.7 years) and
      23 healthy control children (median age, 9.37 years; range, 6.2-15.4 years),
      using two child-friendly fMRI tasks and adapted data-processing streams. Overall,
      81 functional series could be analyzed. Reorganization seemed to occur primarily
      in homotopic regions in the contralateral hemisphere, but lateralization in the
      frontal as well as in the temporal lobes was significantly different between
      patients and controls. The likelihood to find atypical language organization was
      significantly higher in patients. Additionally, we found significantly stronger
      activation in the healthy controls in a primarily passive task, suggesting a
      systematic confounding influence of antiepileptic medication. The presence of a
      focal cortical dysplasia was significantly associated with atypical language
      lateralization. We conclude that important confounds need to be considered and
      that the pattern of language reorganization may be distinct from the patterns
      seen in later-onset epilepsy.

PMID- 21181814
TI  - Herbert Waldmann.

PMID- 21181800
TI  - Anxiety positive subjects show altered processing in the anterior insula during
      anticipation of negative stimuli.
AB  - Prior neuroimaging studies support the hypothesis that anticipation, an important
      component of anxiety, may be mediated by activation within the insular and medial
      prefrontal cortices including the anterior cingulate cortex. However, there is an
      insufficient understanding of how affective anticipation differs across anxiety
      groups in emotional brain loci and networks. We examined 14 anxiety positive (AP)
      and 14 anxiety normative (AN) individuals completing an affective picture
      anticipation task during functional magnetic resonance imaging (fMRI). Brain
      activation was examined across groups for cued anticipation (to aversive or
      pleasant stimuli). Both groups showed greater activation in the bilateral
      anterior insula during cued differential anticipation (i.e., aversive vs.
      pleasant), and activation on the right was significantly higher in AP compared to
      AN subjects. Functional connectivity showed that the left anterior insula was
      involved in a similar network during pleasant anticipation in both groups. The
      left anterior insula during aversive and the right anterior insula during all
      anticipation conditions coactivated with a cortical network consisting of frontal
      and parietal lobes in the AP group to a greater degree. These results are
      consistent with the hypothesis that anxiety is related to greater anticipatory
      reactivity in the brain and that there may be functional asymmetries in the brain
      that interact with psychiatric traits.

PMID- 21181834
TI  - An exceptionally active catalyst for generating hydrogen from water.

PMID- 21181827
TI  - Intelligent microflow: development of self-optimizing reaction systems.

PMID- 21181845
TI  - Molecular recognition of beta-O-GlcNAc glycopeptides by a lectin-like receptor:
      binding modulation by the underlying Ser or Thr amino acids.
AB  - The binding properties of different carbohydrates and glycopeptides containing
      the beta-O-2-deoxy-2-(N-acetyl)-D-glucosaminyl (beta-O-GlcNAc) to a synthetically
      prepared lectin-like receptor have been analyzed. The study combines the use of
      NMR spectroscopy experiments with extensive MD simulations in explicit water.
      Notably, the presence of a key hydrogen bond between the receptor and the OMe
      group of the beta-O-GlcNAc-OMe derivative appears to be responsible for the high
      selectivity observed for this compound. In addition, to study the effect on the
      binding of the underlying amino acid, we have prepared different model
      glycopeptides, which include the non-natural alpha-methylserine and alpha
      methylthreonine as underlying amino acids. Interestingly, the presence of a
      methyl group decreases the affinity constant, especially in those cases in which
      a beta-methyl group is present. As a result, the serine-containing glycopeptide
      exhibited the highest affinity constant of the glycopeptides, and the threonine
      derivative showed the lowest one. This low selectivity could have its origin in
      the difficulty to form both specific hydrogen bonds and hydrophobic (CH-pi)
      contacts.

PMID- 21181846
TI  - Elucidation of the biosynthesis and degradation of allantofuranone by isotopic
      labelling and fermentation of modified precursors.
AB  - Feeding experiments with the ascomycete Allantophomopsis lycopodina indicated
      that the potent fungistatic allantofuranone is biosynthesized from phenylalanine.
      Further experiments with synthetic precursors gave evidence that the naturally
      occurring polyporic acid serves as a key intermediate in the biosynthesis. In
      addition to the formation of allantofuranone, its abiotic and metabolic
      degradation were investigated.

PMID- 21181847
TI  - Nonenzymatic ubiquitylation.

PMID- 21181850
TI  - Gold(III) complexes of asymmetrically aryl-substituted 1,2-dithiolene ligands
      featuring potential-controlled spectroscopic properties: an insight into the
      electronic properties of bis(pyren-1-yl-ethylene-1,2-dithiolato)gold(III).
AB  - The electrochemical, UV/Vis-NIR absorption, and emission-spectroscopic features
      of (TBA(+))(1(-)) and the corresponding neutral complex 1 were investigated
      (TBA(+)=tetrabutylammonium; 1(-)=[Au(III)(Pyr,H-edt)(2)](-); Pyr,H-edt(2-)=pyren
      1-yl-ethylene-1,2-dithiolato). The intense electrochromic NIR absorption
      (lambda(max)=1432 nm; epsilon=13000 M(-1) cm(-1) in CH(2)Cl(2)) and the potential
      controlled visible emission in the range 400-500 nm, the energy of which depends
      on the charge of the complex, were interpreted on the grounds of time-dependent
      DFT calculations carried out on the cis and trans isomers of 1, 1(-), and 1(2-).
      In addition, to evaluate the nonlinear optical properties of 1(x-) (x=0, 1),
      first static hyperpolarizability values beta(tot) were calculated
      (beta(tot)=78*10(-30) and 212*10(-30) esu for the cis isomer of 1(-) and 1,
      respectively) and compared to those of differently substituted [Au(Ar,H
      edt)(2)](x-) gold dithiolenes [Ar=naphth-2-yl (2), phenyl (3); x=0, 1].

PMID- 21181851
TI  - New insights into Keggin-type 12-tungstophosphoric acid from 31P MAS NMR analysis
      of absorbed trimethylphosphine oxide and DFT calculations.
AB  - The acid and transport properties of the anhydrous Keggin-type 12
      tungstophosphoric acid (H(3)PW(12)O(40); HPW) have been studied by solid-state
      (31)P magic-angle spinning NMR of absorbed trimethylphosphine oxide (TMPO) in
      conjunction with DFT calculations. Accordingly, (31)P NMR resonances arising from
      various protonated complexes, such as TMPOH(+) and (TMPO)(2)H(+) adducts, could
      be unambiguously identified. It was found that thermal pretreatment of the sample
      at elevated temperatures (>=423 K) is a prerequisite for ensuring complete
      penetration of the TMPO guest probe molecule into HPW particles. Transport of the
      TMPO absorbate into the matrix of the HPW adsorbent was found to invoke a
      desorption/absorption process associated with the (TMPO)(2)H(+) adducts.
      Consequently, three types of protonic acid sites with distinct superacid
      strengths, which correspond to (31)P chemical shifts of 92.1, 89.4, and 87.7 ppm,
      were observed for HPW samples loaded with less than three molecules of TMPO per
      Keggin unit. Together with detailed DFT calculations, these results support the
      scenario that the TMPOH(+) complexes are associated with protons located at three
      different terminal oxygen (O(d)) sites of the PW(12)O(40)(3-) polyanions. Upon
      increasing the TMPO loading to >3.0 molecules per Keggin unit, abrupt decreases
      in acid strength and the corresponding structural variations were attributed to
      the change in secondary structure of the pseudoliquid phase of HPW in the
      presence of excessive guest absorbate.

PMID- 21181854
TI  - 2D hexagonal tilings based on triangular and hexagonal structural units in the
      self-assembly of thiacalix[4]arene tetrasulfonate on an Au(111) surface.
AB  - The formation of several molecular 2D tilings with long-range periodicity,
      including the Kagome network, distorted Kagome network, and snub trihexagonal
      tiling from the adsorption and assembly of thiacalix[4]arene tetrasulfonate
      (TCAS) at the 0.1 M HClO(4)/Au(111) interface has been investigated by
      electrochemical scanning tunneling microscopy (STM). The internal structures of
      the tilings have been disclosed by high-resolution STM images. The basic
      structural motifs, namely, the tiles of these tilings are similar, including
      triangular units and hexagonal units. Due to the different arrangement of the
      molecules within the triangular units, tiles with different configurations are
      formed, which further result in the polymorphism of the 2D tiling. This result is
      of significance for understanding the formation of 2D tiling as well as the
      design and construction of molecular self-assembled nanostructures.

PMID- 21181860
TI  - Electrophysiologic recurrent laryngeal nerve monitoring during thyroid and
      parathyroid surgery: international standards guideline statement.
AB  - Intraoperative neural monitoring (IONM) during thyroid and parathyroid surgery
      has gained widespread acceptance as an adjunct to the gold standard of visual
      nerve identification. Despite the increasing use of IONM, review of the
      literature and clinical experience confirms there is little uniformity in
      application of and results from nerve monitoring across different centers. We
      provide a review of the literature and cumulative experience of the
      multidisciplinary International Neural Monitoring Study Group with IONM spanning
      nearly 15 years. The study group focused its initial work on formulation of
      standards in IONM as it relates to important areas: 1) standards of equipment
      setup/endotracheal tube placement and 2) standards of loss of signal
      evaluation/intraoperative problem-solving algorithm. The use of standardized
      methods and reporting will provide greater uniformity in application of IONM. In
      addition, this report clarifies the limitations of IONM and helps identify areas
      where additional research is necessary. This guideline is, at its forefront,
      quality driven; it is intended to improve the quality of neural monitoring, to
      translate the best available evidence into clinical practice to promote best
      practices. We hope this work will minimize inappropriate variations in monitoring
      rather than to dictate practice options.

PMID- 21181869
TI  - How can social network analysis improve the study of primate behavior?
AB  - When living in a group, individuals have to make trade-offs, and compromise, in
      order to balance the advantages and disadvantages of group life. Strategies that
      enable individuals to achieve this typically affect inter-individual interactions
      resulting in nonrandom associations. Studying the patterns of this assortativity
      using social network analyses can allow us to explore how individual behavior
      influences what happens at the group, or population level. Understanding the
      consequences of these interactions at multiple scales may allow us to better
      understand the fitness implications for individuals. Social network analyses
      offer the tools to achieve this. This special issue aims to highlight the
      benefits of social network analysis for the study of primate behaviour, assessing
      it's suitability for analyzing individual social characteristics as well as
      group/population patterns. In this introduction to the special issue, we first
      introduce social network theory, then demonstrate with examples how social
      networks can influence individual and collective behaviors, and finally conclude
      with some outstanding questions for future primatological research.

PMID- 21181874
TI  - First captive breeding of the imperial parrot (Amazona imperialis).
AB  - We describe the rearing and development of the first imperial parrot (Amazona
      imperialis) hatched and raised in captivity. A single egg was hen-incubated for
      28 days, and the chick was parent-fed for ~14 days, after which it was removed
      for hand-rearing. Similar to wild, parent-reared imperial nestlings, the chick
      developed fully within 12 weeks, weaning at 540 g body weight. Endangered and
      endemic to Dominica, the imperial is a vital flagship for oceanic rainforest
      conservation. Chronicling the neonatal development of A. imperialis helps
      illuminate the natural history of this enigmatic species, whose secretive nesting
      habits and low population density have frustrated a detailed understanding of its
      ecology and reproduction.

PMID- 21181886
TI  - Noncanonical Wnt signaling in vertebrate development, stem cells, and diseases.
AB  - Wnt signaling regulates many aspects of vertebrate development and adult stem
      cells. Deregulation of Wnt signaling causes development defect and cancer. The
      signaling is categorized in two pathways: canonical and noncanonical. Both
      pathways are initiated by Wnt ligands and Frizzled receptors. Canonical pathway
      leads to beta-catenin:T-cell factor/lymphoid enhancer factor-mediated gene
      expression, which regulates proliferation and differentiation of cells.
      Noncanonical Wnt signaling is mediated by intracellular calcium ion and JNK. This
      signaling leads to NFAT, a key transcriptional factor regulating gene expression.
      In addition, beta-catenin:T-cell factor/lymphoid enhancer factor-mediated gene
      expression is downregulated by CaMKII-TAK1-NLK. Cellular polarity and motility
      are the main outcomes of the signaling. During development, noncanonical Wnt
      signaling is required for tissue formation. Recent studies have shown that
      atypical cadherin Flamingo contributes to noncanonical Wnt signaling by directing
      the migration of cells. Also, noncanonical Wnt signaling is required for
      maintenance of adult stem cells. In the field of cancer research, noncanonical
      Wnt signaling has been considered a tumor suppressor; however, recent evidence
      has shown that the signaling also enhances cancer progression in the later stages
      of disease. In this review, we describe and discuss components of noncanonical
      Wnt signaling, diseases caused by deregulation of the signaling, regulation of
      adult stem cells by the signaling, and implications in cancer biology.

PMID- 21181885
TI  - Establishment and regulation of the HSC niche: Roles of osteoblastic and vascular
      compartments.
AB  - Hematopoietic stem cells (HSC) are multi-potent cells that function to generate a
      lifelong supply of all blood cell types. During mammalian embryogenesis, sites of
      hematopoiesis change over the course of gestation: from extraembryonic yolk sac
      and placenta, to embryonic aorta-gonad-mesonephros region, fetal liver, and
      finally fetal bond marrow where HSC reside postnatally. These tissues provide
      microenviroments for de novo HSC formation, as well as HSC maturation and
      expansion. Within adult bone marrow, HSC self-renewal and differentiation are
      thought to be regulated by two major cellular components within their so-called
      niche: osteoblasts and vascular endothelial cells. This review focuses on HSC
      generation within, and migration to, different tissues during development, and
      also provides a summary of major regulatory factors provided by osteoblasts and
      vascular endothelial cells within the adult bone marrow niche.

PMID- 21181887
TI  - Mesenchymal stem cells from development to postnatal joint homeostasis, aging,
      and disease.
AB  - Joint morphogenesis involves signaling pathways and growth factors that recur in
      the adult life with less redundancy to safeguard joint homeostasis. Loss of such
      homeostasis due to abnormal signaling networks as in aging could lead to diseases
      such as osteoarthritis. Stem cells are the cellular counterpart and targets of
      the morphogenetic signals, and they function to maintain the tissues by ensuring
      replacement of cells lost to physiological turnover, injury, aging, and disease.
      Mesenchymal stem cells (MSCs) are key players in regenerative medicine for their
      ability to differentiate toward multiple lineages such as cartilage and bone, but
      they age along the host body and senesce when serially passaged in culture.
      Understanding correlations between aging and its effects on MSCs is of the utmost
      importance to explain how aging happens and unravel the underlying mechanisms.
      The investigation of the MSC senescence in culture will help in developing more
      efficient and standardized cell culture methods for cellular therapies in
      skeletal regenerative medicine. An important area to explore in biomedical
      sciences is the role of endogenous stem cell niches in joint homeostasis,
      remodeling, and disease. It is anticipated that an understanding of the stem cell
      niches and related remodeling signals will allow the development of
      pharmacological interventions to support effective joint tissue regeneration, to
      restore joint homeostasis, and to prevent osteoarthritis.

PMID- 21181889
TI  - Adult hippocampal neurogenesis in aging and Alzheimer's disease.
AB  - Adult neurogenesis occurs in the subgranular zone of the hippocampal dentate
      gyrus and the subventricular zone of the lateral ventricles. This process is
      highly regulated by intrinsic and extrinsic factors, which may control the
      proliferation and/or maturation of neural progenitor cells. Adult-born neurons
      are integrated in preexisting networks and may have functional implications for
      adult brain. Here we attempt to summarize relevant findings concerning the
      physiological role of adult neurogenesis mainly focused on the subgranular zone,
      and to discuss the reduced neurogenesis observed during aging and the factors
      that have been involved in this phenomenon. Finally, we focus on hippocampal
      neurogenesis in Alzheimer's disease, reviewing animal models of the disease used
      for the study of this process and the conclusions that have been drawn in this
      context.

PMID- 21181890
TI  - Telomere, DNA damage, and oxidative stress in stem cell aging.
AB  - "Stem cell aging" is a novel concept that developed together with the advances of
      stem cell biology, especially the sophisticated prospectively isolation and
      characterization of multipotent somatic tissue stem cells. Although being
      immortal in principle, stem cells can also undergo aging processes and
      potentially contribute to organismal aging. The impact of an age-dependent
      decline of stem cell function weighs differently in organs with high or low rates
      of cell turnover. Nonetheless, most of the organ systems undergo age-dependent
      loss of homeostasis and functionality, and emerging evidence showed that this has
      to do with the aging of resident stem cells in the organ systems. The mechanisms
      of stem cell aging and its real contribution to human aging remain to be defined.
      Many antitumor mechanisms protect potential malignant transformation of stem cell
      by inducing apoptosis or senescence but simultaneously provoke stem cell aging.
      In this review, we try to discuss several concept of stem cell aging and
      summarize recent progression on the molecular mechanisms of stem cell aging.

PMID- 21181888
TI  - Stem Leydig cells: from fetal to aged animals.
AB  - Leydig cells are the testosterone-producing cells of the testis. The adult Leydig
      cell (ALC) population ultimately develops from undifferentiated mesenchymal-like
      stem cells present in the interstitial compartment of the neonatal testis.
      Distinct stages of ALC development have been identified and characterized. These
      include stem Leydig cells (SLCs), progenitor Leydig cells, immature Leydig cells,
      and ALCs. This review describes our current understanding of the SLCs in the
      fetal, prenatal, peripubertal, adult, and aged rat testis, as well as recent
      studies of the differentiation of steroidogenic cells from the stem cells of
      other organs.

PMID- 21181892
TI  - Diadem/crater defect in spermatozoa of a Brahman bull: Seminal traits,
      microscopic findings and IVF fertility. Genetic predisposition?

PMID- 21181893
TI  - Postassociation cleaning using linkage disequilibrium information.
AB  - In genetic association studies, quality control (QC) filters are applied to
      remove potentially problematic markers before the markers are tested for
      statistical associations. However, spurious associations can still occur after
      QC. We introduce Post-Association Cleaning (PAC) approach that can complement QC
      by capturing spurious associations using the information in the post-association
      results. Specifically, we propose a PAC filter based on the linkage
      disequilibrium (LD) information. The intuition is that if the association is
      caused by a true genetic effect, neighboring markers in LD should show comparably
      significant P-values. If not, it may be evidence of spurious association.
      Previous studies have applied the same idea but only manually without a formal
      statistical framework. Our proposed method LD-PAC provides a systematic framework
      to quantitatively measure the evidence of spurious associations based on the
      likelihood ratio. Simulations show that LD-PAC can detect spurious associations
      with high detection rate (84%). In addition to detecting spurious associations,
      our method can also be used to "rescue" candidate associations from the
      supposedly unclean data such as the markers excluded by QC. Although the
      additional associations must be treated with care, they can suggest interesting
      regions. The application of our method to the Wellcome Trust Case Control
      Consortium (WTCCC) data led to the discovery of an additional candidate
      association for type 1 diabetes among the QC-excluded markers. This locus turns
      out to be in a region recently identified as significant by a meta-analysis
      performed after the WTCCC study was published.

PMID- 21181895
TI  - Investigation of maternal effects, maternal-fetal interactions and parent-of
      origin effects (imprinting), using mothers and their offspring.
AB  - Many complex genetic effects, including epigenetic effects, may be expected to
      operate via mechanisms in the inter-uterine environment. A popular design for the
      investigation of such effects, including effects of parent-of-origin
      (imprinting), maternal genotype, and maternal-fetal genotype interactions, is to
      collect DNA from affected offspring and their mothers (case/mother duos) and to
      compare with an appropriate control sample. An alternative design uses data from
      cases and both parents (case/parent trios) but does not require controls. In this
      study, we describe a novel implementation of a multinomial modeling approach that
      allows the estimation of such genetic effects using either case/mother duos or
      case/parent trios. We investigate the performance of our approach using computer
      simulations and explore the sample sizes and data structures required to provide
      high power for detection of effects and accurate estimation of the relative risks
      conferred. Through the incorporation of additional assumptions (such as Hardy
      Weinberg equilibrium, random mating and known allele frequencies) and/or the
      incorporation of additional types of control sample (such as unrelated controls,
      controls and their mothers, or both parents of controls), we show that the
      (relative risk) parameters of interest are identifiable and well estimated.
      Nevertheless, parameter interpretation can be complex, as we illustrate by
      demonstrating the mathematical equivalence between various different
      parameterizations. Our approach scales up easily to allow the analysis of large
      scale genome-wide association data, provided both mothers and affected offspring
      have been genotyped at all variants of interest.

PMID- 21181896
TI  - The Maximum-Likelihood-Binomial method revisited: a robust approach for model
      free linkage analysis of quantitative traits in large sibships.
AB  - Model-free linkage analysis methods, based on identity-by-descent allele sharing,
      are commonly used for complex trait analysis. The Maximum-Likelihood-Binomial
      (MLB) approach, which is based on the hypothesis that parental alleles are
      binomially distributed among affected sibs, is particularly popular. An extension
      of this method to quantitative traits (QT) has been proposed (MLB-QTL), based on
      the introduction of a latent binary variable capturing information about the
      linkage between the QT and the marker. Interestingly, the MLB-QTL method does not
      require the decomposition of sibships into constituent sibpairs and requires no
      prior assumption about the distribution of the QT. We propose a new formulation
      of the MLB method for quantitative traits (nMLB-QTL) that explicitly takes
      advantage of the independence of paternal and maternal allele transmission under
      the null hypothesis of no linkage. Simulation studies under H0 showed that the
      nMLB-QTL method generated very consistent type I errors. Furthermore, simulations
      under the alternative hypothesis showed that the nMLB-QTL method was slightly,
      but systematically more powerful than the MLB-QTL method, whatever the genetic
      model, residual correlation, ascertainment strategy and sibship size considered.
      Finally, the power of the nMLB-QTL method is illustrated by a chromosome-wide
      linkage scan for a quantitative endophenotype of leprosy infection. Overall, the
      nMLB-QTL method is a robust, powerful, and flexible approach for detecting
      linkage with quantitative phenotypes, particularly in studies of non Gaussian
      phenotypes in large sibships.

PMID- 21181894
TI  - Meta-analysis of gene-environment interaction: joint estimation of SNP and SNP *
      environment regression coefficients.
AB  - INTRODUCTION: Genetic discoveries are validated through the meta-analysis of
      genome-wide association scans in large international consortia. Because
      environmental variables may interact with genetic factors, investigation of
      differing genetic effects for distinct levels of an environmental exposure in
      these large consortia may yield additional susceptibility loci undetected by main
      effects analysis. We describe a method of joint meta-analysis (JMA) of SNP and
      SNP by Environment (SNP * E) regression coefficients for use in gene-environment
      interaction studies. METHODS: In testing SNP * E interactions, one approach uses
      a two degree of freedom test to identify genetic variants that influence the
      trait of interest. This approach detects both main and interaction effects
      between the trait and the SNP. We propose a method to jointly meta-analyze the
      SNP and SNP * E coefficients using multivariate generalized least squares. This
      approach provides confidence intervals of the two estimates, a joint significance
      test for SNP and SNP * E terms, and a test of homogeneity across samples.
      RESULTS: We present a simulation study comparing this method to four other
      methods of meta-analysis and demonstrate that the JMA performs better than the
      others when both main and interaction effects are present. Additionally, we
      implemented our methods in a meta-analysis of the association between SNPs from
      the type 2 diabetes-associated gene PPARG and log-transformed fasting insulin
      levels and interaction by body mass index in a combined sample of 19,466
      individuals from five cohorts.

PMID- 21181897
TI  - Bayesian analysis of rare variants in genetic association studies.
AB  - Recent advances in next-generation sequencing technologies facilitate the
      detection of rare variants, making it possible to uncover the roles of rare
      variants in complex diseases. As any single rare variants contain little
      variation, association analysis of rare variants requires statistical methods
      that can effectively combine the information across variants and estimate their
      overall effect. In this study, we propose a novel Bayesian generalized linear
      model for analyzing multiple rare variants within a gene or genomic region in
      genetic association studies. Our model can deal with complicated situations that
      have not been fully addressed by existing methods, including issues of disparate
      effects and nonfunctional variants. Our method jointly models the overall effect
      and the weights of multiple rare variants and estimates them from the data. This
      approach produces different weights to different variants based on their
      contributions to the phenotype, yielding an effective summary of the information
      across variants. We evaluate the proposed method and compare its performance to
      existing methods on extensive simulated data. The results show that the proposed
      method performs well under all situations and is more powerful than existing
      approaches.

PMID- 21181898
TI  - Direct assessment of multiple testing correction in case-control association
      studies with related individuals.
AB  - Genome-wide association studies typically test large numbers of genetic variants
      in association with trait values. It is well known that linkage disequilibrium
      (LD) between nearby markers tends to introduce correlation among association
      tests. Failure to properly adjust for multiple comparisons can lead to false
      positive results or missing true-positive signals. The Bonferroni correction is
      generally conservative in the presence of LD. The permutation procedure, although
      has been widely employed to adjust for correlated tests, is not applicable when
      related individuals are included in case-control samples. With related
      individuals, the dependence among relatives' genotypes can also contribute to the
      correlation between tests. We present a new method P(norm) to correct for
      multiple hypothesis testing in case-control association studies in which some
      individuals are related. The adjustment with P(norm) simultaneously accounts for
      two sources of correlations of the test statistics: (1) LD among genetic markers
      (2) dependence among genotypes across related individuals. Using simulated data
      based on the International HapMap Project, we demonstrate that it has better
      control of type I error and is more powerful than some of the recently developed
      methods. We apply the method to a genome-wide association study of alcoholism in
      the GAW 14 COGA data set and detect genome-wide significant association.

PMID- 21181899
TI  - Ancestry informative marker panels for African Americans based on subsets of
      commercially available SNP arrays.
AB  - Admixture mapping is a widely used method for localizing disease genes in African
      Americans. Most current methods for inferring ancestry at each locus in the
      genome use a few thousand single nucleotide polymorphisms (SNPs) that are very
      different in frequency between West Africans and European Americans, and that are
      required to not be in linkage disequilibrium in the ancestral populations. Modern
      SNP arrays provide data on hundreds of thousands of SNPs per sample, and to use
      these to infer ancestry, using many of the standard methods, it is necessary to
      choose subsets of the SNPs for analysis. Here we present panels of about 4,300
      ancestry informative markers (AIMs) that are subsets respectively of SNPs on the
      Illumina 1 M, Illumina 650, Illumina 610, Affymetrix 6.0 and Affymetrix 5.0
      arrays. To validate the usefulness of these panels, we applied them to samples
      that are different from the ones used to select the SNPs. The panels provide
      about 80% of the maximum information about African or European ancestry, even
      with up to 10% missing data.

PMID- 21181908
TI  - Evaluating mutant mtDNA tissue distribution in early fetal development.

PMID- 21181909
TI  - Stepwise functional assessment of unclassified DNA variants.

PMID- 21181911
TI  - Changes in the HIV-1 mutational profile before first-line HAART in the RESINA
      cohort.
AB  - Sporadic observations have shown changing patterns of transmitted drug resistance
      mutations (TDRMs) in HIV infection even without selection pressure by
      antiretroviral treatment (ART). Repeated genotypic resistance analyses in
      treatment-naive patients were performed, in order to analyze intraindividual
      variances of resistance patterns over time. Between the years 2001 and 2008 two
      genotypic resistance tests were performed at different time-points in 49
      treatment-naive HIV-positive patients aged >18 years. Wild-type virus was found
      at baseline and during follow-up in 31 patients (group A, median time between
      resistance tests 146 days), while resistance mutations were found either at
      baseline or during follow-up in 18 patients (group B, median time between
      resistance tests 297 days). In group B, the pattern of resistance changed in
      eight out of 18 patients over time, with three patients showing decreasing
      numbers and five patients showing increasing numbers of resistance mutations. The
      pattern of resistance mutations remained unchanged in 10 out of 18 patients. The
      mutational pattern in untreated HIV infection may change over time and a single
      resistance analysis may underestimate the true prevalence of preserved resistance
      mutations. If these findings can be confirmed in a larger number of patients, it
      would be prudent to perform genotypic resistance testing both at baseline and
      prior to the start of ART in order to capture a more complete picture of
      preserved mutations before initiating ART.

PMID- 21181912
TI  - Seroepidemiology of hepatitis A virus infection among schoolchildren in Taiwan.
AB  - Taiwan was a hyperendemic area for hepatitis A virus (HAV) infection before 1980.
      The aim of this study was to examine the association between seropositivity of
      antibodies against HAV (anti-HAV) by a community-based survey. School children
      from 10 elementary and 3 junior high schools, as well as staff members who worked
      at the above schools in central Taiwan were selected at random in this study.
      Anti-HAV was tested in sera of 1,954 healthy schoolchildren (aged 7-15 years old)
      and 254 teachers by enzyme-linked immunosorbent assay. Schoolchildren had a low
      prevalence of anti-HAV (2.3%) in contrast to the high seroprevalence in their
      teachers (52%). The seropositive rates of HAV antibody among the study subjects
      were increasing with age. No significant differences of anti-HAV seroprevalence
      among the study subjects were observed when they were stratified by gender,
      geographical area, household members, and parental education. Whereas, the anti
      HAV seroprevalence was significantly higher in schoolchildren who were either
      aboriginal or living in areas without a supply of drinking tap-water. The
      seroprevalence of HAV data among the healthy pediatric population would be
      helpful to evaluate the need for mass vaccination policies.

PMID- 21181913
TI  - Hepatitis A viral load in relation to severity of the infection.
AB  - A correlation between hepatitis A virus (HAV) genomes and the clinical severity
      of hepatitis A has not been established. The viral load in sera of hepatitis A
      patients was examined to determine the possible association between hepatitis A
      severity and HAV replication. One hundred sixty-four serum samples from 91
      Japanese patients with sporadic hepatitis A, comprising 11 patients with
      fulminant hepatitis, 10 with severe acute hepatitis, and 70 with self-limited
      acute hepatitis, were tested for HAV RNA. The sera included 83 serial samples
      from 20 patients. Viral load was measured by real-time RT-PCR. The detection
      rates of HAV RNA from fulminant, severe acute, and acute hepatitis were 10/11
      (91%), 10/10 (100%), and 55/70 (79%), respectively. Mean values of HAV RNA at
      admission were 3.48 +/- 1.30 logcopies/ml in fulminant, 4.19 +/- 1.03 in severe
      acute, and 2.65 +/- 1.64 in acute hepatitis. Patients with severe infection such
      as fulminant hepatitis and severe acute hepatitis had higher initial viral load
      than patients with less severe infection (P < 0.001). Viremia persisted for 14.2
      +/- 5.8 days in patients with severe infection and 21.4 +/- 10.6 days in those
      with acute hepatitis after clinical onset (P = 0.19). HAV RNA was detectable
      quantitatively in the majority of the sera of hepatitis A cases during the early
      convalescent phase by real-time PCR. Higher initial viral replication was found
      in severely infected patients. An excessive host immune response might follow,
      reducing the viral load rapidly as a result of the destruction of large numbers
      of HAV-infected hepatocytes, and in turn severe disease might be induced.

PMID- 21181914
TI  - The use of dried blood spots for assessing antibody response to hepatitis A virus
      after natural infection and vaccination.
AB  - During recent years, vaccination against hepatitis A has been implemented in
      several countries. It is expected that the increase in mass vaccination against
      hepatitis A will eventually result in a decreased prevalence of anti-HAV
      antibodies in the general population. For this reason, a suitable clinical sample
      for diagnosis of hepatitis A must be sufficiently sensitive to enable detection
      of lower antibodies titers. In this study, the feasibility of using dried blood
      spots (DBS) was assessed for the detection of anti-HAV antibodies after a natural
      infection and vaccination. Seventy-four DBS and paired plasma samples were
      obtained from a group of college students for a cross-sectional hepatitis A
      seroepidemiological study. Forty-six students seronegative for anti-HAV were
      selected randomly and immunized with an inactivated hepatitis A vaccine using an
      0-6 month schedule. Seroconversion was monitored in paired plasma and DBS samples
      6 months after the first dose followed by a period of 8 and 24 months after the
      second dose. A strong correlation between OD/CO rates of paired plasma and DBS
      samples for the detection of anti-HAV was observed. The sensitivity and
      specificity of the DBS compared with plasma for the detection of anti-HAV
      antibodies after natural infection was 100%. The sensitivity of DBS in samples
      collected 24 months after the second dose of hepatitis A vaccine was 95.4%. The
      results showed that DBS samples can be used for the detection of anti-HAV
      antibodies both after natural infection or vaccination.

PMID- 21181915
TI  - Presence of valine at position 27 of the hepatitis B virus core gene is
      associated with severe liver inflammation in Chinese patients.
AB  - Although it is widely believed that cytotoxic T lymphocytes (CTL) are responsible
      for severe flares of chronic hepatitis B that lead to liver failure, the
      published evidence to support this hypothesis is weak. The frequency of the I27V
      mutation in the HBV core gene, which produces a core 18-27 peptide capable of
      binding HLA-A*02, was compared in Chinese patients with severe liver inflammation
      (n = 77, including 39 with acute-on-chronic liver failure), moderate liver
      inflammation (n = 44) and inactive disease (n = 45). The frequency with which V27
      reverted to the wild-type I27 was compared in severe liver inflammation patients
      who were either HLA-A*02 positive (n = 5) or negative (n = 5). The frequency of
      patients with a V27 positive HBV was higher in severe than in moderate liver
      inflammation (23.4% vs. 6.8%, P = 0.02) or inactive disease (23.4% vs. 4.7%, P =
      0.006). After a minimum of 3 months follow-up, the frequency of reversion of V27
      to the wild-type I27 was higher in HLA-A*02 positive than negative patients (5/5
      vs. 1/5, P = 0.05). In summary, this is the first data showing an association
      between a specific amino acid mutation (I27V) and severe liver inflammation in
      patients with chronic hepatitis B. This mutation would produce a peptide that is
      known to bind HLA-A*02 and stimulate CTL. The high frequency of reversion to wild
      type I27 in HLA-A*02 positive subjects suggests that CTL recognizing this peptide
      exist, and is consistent with the possibility that they contribute to the
      pathophysiology of severe liver inflammation in chronic hepatitis B.

PMID- 21181916
TI  - Another novel subgenotype of hepatitis B virus genotype C from papuans of
      Highland origin.
AB  - Hepatitis B virus (HBV) genotypes and subtypes have been identified worldwide. As
      HBV genotypes/subtypes, the HBV subgenotypes seem to be associated with their
      geographical distribution and ethnic origin. A previous study showed the novel
      HBV subgenotype C6 based on the complete genome sequences of isolates in Papua,
      Indonesia. In the present study, further characterization of HBV in Jayapura
      (capital of Papua Province), particularly from native people of Papua originating
      from the highland (highland Papuans) and those from the lowland (lowland Papuans)
      were examined. Of 32 HBV isolates from both highland and lowland Papuan blood
      donors with HBsAg positive, part of the S gene and the core gene sequences were
      analyzed. Analyses of some isolates from highland Papuans were confirmed by the
      complete genome sequences. Most HBV isolates were classified into genotype C
      (78.1%), followed by genotype B (18.8%), and genotype D (3.1%). The subtype adr
      was predominant (71.9%), followed by adw2 (25.1%), and ayw2 (3.1%). As with
      previous findings, phylogenetic analyses revealed that most HBV isolates from
      Papuans, C/adr, belonged to subgenotype C6. Interestingly, some C/adr isolates
      from highland Papuans formed a distinct cluster from all reported subgenotypes of
      HBV/C, and they differed from HBV/C1-C10 by 4.2-7.2% over the complete genome.
      SimPlot analysis showed no evidence of recombination with HBV/C1-C10. The
      isolated life and closed social systems of highland Papuans, even though some
      have been moving to Jayapura, likely contribute to the formation of this unique
      cluster of infection with a novel subgenotype of HBV, named C11.

PMID- 21181917
TI  - Molecular characterization of hepatitis B virus isolates from Zimbabwean blood
      donors.
AB  - Hepatitis B virus (HBV) is endemic in Africa, being hyperendemic in sub-Saharan
      Africa. Genotypes A, D, and E circulate in Africa, showing a distinct
      geographical distribution. The aim of the present study was to determine the HBV
      genotype distribution in blood donors from different geographical locations in
      Zimbabwe. Using a restriction fragment polymorphism assay, sequencing of the
      basic core promoter/precore region and of the complete S open reading frame
      showed that 29 HBV isolates from geographically distinct regions belong to
      subgenotype A1. The complete genome of two of these Zimbabwean HBV isolates was
      sequenced. Forty-four percent of the Zimbabwean HBV isolates (11/23) were
      characterized by a G1862C missense mutation, which causes a Val to Leu amino acid
      substitution at position 17 of the precore region. The majority of Zimbabwean HBV
      isolates clustered with a number of South African HBV isolates, with which they
      shared characteristic amino acids in the preS1, preS2, and polymerase spacer
      regions. The wide distribution of subgenotype in Africa, as well as the high
      intragroup divergence and the geographical clustering of the African and Asian
      subgenotype A1 HBV isolates indicate that this subgenotype has a long period of
      endemicity in these regions.

PMID- 21181918
TI  - Molecular epidemiology of chronic hepatitis B virus infection in Greece.
AB  - Virological data on chronic hepatitis B virus (HBV) infection in Greece are
      limited. HBV genotypes, surface antigen (HBsAg) subtypes, and HBsAg "a"
      determinant mutations among patients infected chronically with HBV, were
      investigated. Serum samples from 135 HBsAg positive patients were tested.
      Serologic (HBsAg, anti-HBs, HBeAg, and anti-HBe), virologic (HBV-DNA
      quantitation) and biochemical markers (serum alanine aminotransferase/ALT and
      aspartate aminotransferase/AST) were analyzed. HBV genotypes and HBsAg subtypes
      were determined by partial sequencing of the S gene. Genotyping was performed by
      using the National Center for Biotechnology Information online Genotyping tool
      and phylogenetic analysis. Nucleotide sequences were aligned pair wise with
      ClustalW and phylogenetic trees were constructed by the neighbor-joining method.
      Sequences were also used to predict HBV HBsAg subtypes. In six patients (4%),
      simultaneous presence of HBsAg and anti-HBs was determined, whereas 47 patients
      (35%) were HBeAg positive, 84 (62.5%) were anti-HBe positive, and four patients
      (3%) were characterized by the simultaneous presence of HBeAg and anti-HBe. Mean
      ALT was 238 IU/L (standard deviation = 576.84), and HBV-DNA levels ranged from
      1.02 * 10(5) to 2.2 * 10(7) IU/ml. Genotype D was predominant (98%), with viral
      groups D/ayw2 (73%) and D/ayw3 (27%). Group A/adw accounted for 1% of cases.
      Genotypes B and C were found exclusively in the Chinese immigrants (1%). Single
      or multiple point mutations were found in 35 cases (26%). Some of the most common
      mutations occurred at amino acid positions 129, 133, 134, 144, 145, including the
      "vaccine escape" mutation G145R. Mutations analysis revealed that amino acid
      substitutions did not affect detection by commercial immunoassays.

PMID- 21181919
TI  - Variations in the functional domain of basal core promoter of hepatitis B virus
      among Eastern Indian patients with prevalence of genotypes A, C, and D among the
      same ethnic population.
AB  - Mutations in the basal core promoter (BCP) and precore (PC) regions are
      associated with persistent and intermittently high hepatitis B virus (HBV)
      replication in several patients. The variability in the functional domains of BCP
      and PC region of HBV and their association with disease progression and clinical
      outcome were assessed in Eastern India, an unique region where three HBV
      genotypes, A, D, and C are prevalent among the same ethnic group. PCR
      amplification and direct sequencing of BCP and PC region was done on sera
      obtained from 130 HBsAg positive subjects with different clinical presentations.
      Associations of the apparent risk factors with clinical advancement were
      evaluated by statistical methods including multiple logistic regression analyses
      (MLR). HBV genotype A was present in 33.08%, C in 25.38%, and D in 41.54% cases.
      Genotypes A and C were associated with higher rate of T1762/A1764 mutations than
      the most predominant genotype D. HBeAg negative state was associated with
      considerably higher rate of C1753 mutation. T1762/A1764 along with C1753 was
      common among cirrhosis and T1762/A1764 without C1753 was frequent among chronic
      liver disease cases. No significant association was found between A1896 point
      mutation and clinical status. Multivariate analysis revealed that T1762/A1764
      double mutation, HBV/A, age >=25 years, C1753 and A1899 were critical factors for
      clinical advancement while age >=25 years and C1753 as significant predictor for
      cirrhosis in comparison with chronic liver disease. In conclusion, the analysis
      of the BCP variability may help in monitoring the progression towards advanced
      liver disease in Eastern Indian patients.

PMID- 21181920
TI  - Hepatitis C infection, Cognition, and inflammation in an Egyptian sample.
AB  - Chronic hepatitis C (HCV) infection is associated with cognitive impairments
      which might be mediated through a secondary inflammatory cascade. Egypt has an
      unusually high prevalence of HCV monoinfections and is an ideal site for the
      study of the isolated effects of HCV infection. Therefore, in a hospital-based
      cross-sectional study based in Egypt, this study compared cognitive functioning
      and serum markers of inflammation in 11 HCV positive cases and 14 HCV negative
      controls. The Wisconsin Card Sorting Test was used to assess cognitive
      flexibility and the Brief Visuospatial Memory Test-Revised was used to assess
      learning and memory. Circulating levels of soluble tumor necrosis factor receptor
      II (sTNFR-II), monocyte chemotactic protein-1 (MCP-1/CCL2), and soluble CD14
      (sCD14) were determined as indices of inflammation. HCV positive cases had higher
      levels of sTNFR-II (t = -3.5, P = 0.002). HCV positive cases also had
      significantly worse cognitive flexibility with higher number of total errors (t =
      -2.18, P = 0.04), and preservative responses (t = -2.12, P = 0.05), and lower
      number of conceptual level responses (t = 1.32, P = 0.04) on the Wisconsin Card
      Sorting test. In conclusion, results from this pilot study indicate that HCV+
      patients have worse cognitive performance and somewhat greater inflammatory
      activity as compared to controls. The increased inflammation may be associated
      with the cognitive impairments observed in these HCV+ patients.

PMID- 21181921
TI  - Multiplex PCR for identification of herpes virus infections in adolescents.
AB  - The aim of the study was to develop a multiplex PCR (mPCR) for a rapid and
      simultaneous detection of herpes simplex 1 (HSV-1), herpes simplex 2 (HSV-2), and
      human cytomegalovirus (HCMV) DNA in squamous oral cells obtained from
      adolescents. Accuracy of the method was tested in a group of 513 adolescents,
      almost 11% of subjects were positive for infection with herpes viruses.
      Correlations with gender, age, and place of residence were sought. A similar
      incidence of HSV-2 and HCMV was found (4.3% and 5.4%, respectively) and the
      incidence of HSV-1 was the lowest (1%) in the study group. Conversely to HSV-2,
      HCMV was detected mostly in the youngest individuals. The same occurrence of all
      viruses was observed in boys and girls. The mPCR method described is suggested as
      a useful tool for epidemiologic studies of active herpes infections.

PMID- 21181922
TI  - Clinical performance of the CLART human papillomavirus 2 assay compared with the
      hybrid capture 2 test.
AB  - Persistent infection by high-risk human papillomavirus (HR-HPV) is a cause of
      cervical cancer. The use of HPV detection in cervical screening programs may
      improve the ability to identify women at risk of cervical cancer. Therefore, the
      development of appropriate methods for the detection of HR-HPV is essential. The
      aim of this study was to evaluate the clinical performance of the CLART Human
      Papillomavirus 2 assay (CLART) in comparison with the Hybrid Capture 2 test
      (HC2), using a clinical cut-off of cervical intraepithelial neoplasia grade 2 or
      worse. Discrepant results were analyzed further by the PapilloCheck HPV
      genotyping system. In the 425 studied women, HR-HPV positivity rates were similar
      by both tests (CLART-13 HR-HPV: 63.1%; CLART-17 HR-HPV: 64.7%; HC2: 64.5%).
      Agreement between CLART-13 HR-HPV (kappa = 0.969; concordance level 98.6%), CLART
      17 HR-HPV (kappa = 0.974; concordance level 98.8%), and HC2 were very good. When
      13 HR-HPV types were considered, the two tests showed a clinical sensitivity of
      96% (95% CI: 92.6-97.9). The clinical specificity of CLART-13 HR-HPV was 73.6%
      (95% CI: 66.7-79.5) for cervical intraepithelial neoplasia grade 2 or worse,
      which was comparable to HC2 (71.4%; 95% CI: 64.3-77.5). When all 17 HR-HPV types
      were considered, CLART showed a clinical sensitivity of 96.9% (95% CI: 93.8-98.5)
      and a clinical specificity of 71.9% (95% CI: 64.9-78.0). In conclusion, the CLART
      assay is efficient, sensitive, reproducible, and has a similar performance to HC2
      for cervical intraepithelial neoplasia grade 2 or worse. Furthermore, this assay
      has the advantage of detecting and genotyping 35 HPV types by a single test,
      which can provide additional information on the predictive value of infection
      with HR-HPV.

PMID- 21181923
TI  - Etiological role of human papillomavirus infection for inverted papilloma of the
      bladder.
AB  - The status of human papillomavirus (HPV) infection in urothelial inverted
      papilloma was examined in the present study. Formalin-fixed and paraffin-embedded
      tissues from eight cases of inverted papilloma of the bladder were studied. The
      presence of HPV-DNA was examined by modified GP5/6+PCR using archival tissue
      sections by microdissection. HPV genotype was determined with a Hybri-Max HPV
      genotyping kit. Immunohistochemical analysis for p16-INK4a, mcm7, HPV-E4, and L1,
      and in situ hybridization for the HPV genome were performed. HPV was detected in
      seven of eight cases (87.5%) of inverted papilloma. Three cases were diagnosed as
      inverted papilloma with atypia, while the remaining five were typical cases. HPV
      18 was detected in two cases, including one inverted papilloma with atypia, and
      HPV-16 was detected in four cases, including one inverted papilloma with atypia.
      Multiple HPV type infection was detected in one typical case and one atypical
      case. High-risk HPV was present in all HPV-positive cases. Cellular proteins, p16
      INK4a and mcm7, which are surrogate markers for HPV-E7 expression, were detected
      in all HPV-positive cases, and their levels were higher in inverted papilloma
      with atypia than in typical cases. In contrast, HPV-E4 and L1, which are markers
      for HPV propagation, were observed in some parts of the typical inverted
      papilloma tissue. High-risk HPV infection may be one of the causes of urothelial
      inverted papilloma, and inverted papilloma with atypia may have malignant
      potential.

PMID- 21181924
TI  - Human bocavirus infection in children with acute gastroenteritis in Japan and
      Thailand.
AB  - A total of 329 fecal specimens, which had been known to be negative for
      rotavirus, adenovirus, norovirus, sapovirus, and astrovirus, and which were
      collected from infants and children with acute gastroenteritis in Japan and
      Thailand during 2005-2008 were screened for human bocavirus (HBoV). HBoV was
      detected by PCR with a primer pair that amplified the NP1 region of its genome
      and was genotyped by sequencing of the VP1/VP2 region. Of the 329 samples tested,
      6 (1.8%) were positive for HBoV. Of these, five samples were collected from Japan
      and one sample was from Thailand, and the detection rates of HBoV in each country
      were 2% and 1.2%, respectively. For the detected HBoV, the capsid VP1/VP2 gene of
      all HBoV strains was successfully sequenced. Four Japanese HBoV strains studied
      were clustered into group 1, while the remaining Japanese strain and a unique
      Thai strain belonged to group 2. No severe acute gastroenteritis associated with
      HBoV was noted. This study provides better understanding on the epidemiology of
      HBoV infections in children with acute gastroenteritis in Japan and Thailand.

PMID- 21181925
TI  - Prevalence of human coronaviruses in adults with acute respiratory tract
      infections in Beijing, China.
AB  - Human coronaviruses (HCoVs) are a common etiological agent of acute respiratory
      tract infections. HCoV infections, especially those caused by the two HCoVs
      identified most recently, NL63 and HKU-1, have not been characterized fully. To
      evaluate the prevalence and clinical presentations of HKU1 and NL63 in adults
      with acute respiratory tract infections, an investigation of HCoV infections in
      Beijing, China from 2005 to 2009 was performed by using reverse transcriptase PCR
      assays and sequencing analysis. Among 8,396 respiratory specimens studied, 87
      (1%) clinical samples were positive for HCoVs, of which 50 samples (0.6% of the
      total) were positive for HCoV-OC43, 15 (0.2%) for HCoV-229E, 14 (0.2%) for HCoV
      HKU1, and 8 (0.1%) for HCoV-NL63. The prevalence of HCoV infection in adults
      exhibited distinct seasonal fluctuations during the study period. In addition,
      patients positive for HCoV-229E infections were more likely to be co-infected
      with other respiratory viruses. Enterovirus, rhinovirus, and parainfluenza virus
      type 3 were the most common viruses found in patients with HCoV infections. The
      demographic and clinical data present in this study of HCoV infections in adults
      with acute respiratory tract infections should improve our understanding of the
      pathogenesis of HCoVs.

PMID- 21181926
TI  - Seroprevalence and serum profile of cytomegalovirus infection among patients with
      hematologic disorders in Bahia State, Brazil.
AB  - Human cytomegalovirus (CMV) is a ubiquitous herpesvirus with from 30% to 100% of
      the general population exhibiting prior exposure by serology. This cross
      sectional study evaluated the serological profile of anti-CMV antibodies and two
      acute-phase reaction proteins in Haematologic Disorder Patients (HDPs) from Bahia
      State, Brazil. Immuno-chemiluminescence assays were performed to detect anti-CMV
      IgM and IgG antibodies. Serological levels of High Sensitivity C-Reactive Protein
      (CRPH) and Alpha-1-Acid Glycoprotein (AAG) were measured using
      immunonephelometry. A total of 470 HDPs were enrolled, 238 (50.6%) males and 232
      (49.4%) females. The overall seroprevalence of CMV was 89.4%, directly
      proportional to age and to the amount of blood units transfused. There was no
      difference between seroprevalence rates according to gender (P = 0.12). Four HDPs
      (0.9%) were seropositives for anti-CMV IgM, only one could be characterized as
      recent acute infection. The most CMV seropositive HDPs had anti-CMV IgG in low
      titers. There was a tendency for females to have higher anti-CMV IgG titers than
      men (P < 0.05). CRPH levels were different among HDPs CMV negative and positive
      groups (P < 0.001). There was no difference in the AAG levels between groups (P =
      0.15). The high CMV seroprevalence found underscores the importance of using
      strategies to provide "CMV safe" blood to HDPs who are at high risk of developing
      severe CMV infection. CRPH can be used as a biomarker associated with CMV
      seropositivity; however, more efforts are needed to better characterize the
      clinical profile of active CMV infection in this group of patients.

PMID- 21181927
TI  - Neutralization of different echovirus serotypes by individual lots of intravenous
      immunoglobulin.
AB  - Replacement therapy using intravenous immunoglobulin (IVIG) preparations in
      people with antibody deficiencies is effective in preventing the majority of
      common bacterial and viral infections, yet echovirus break-through infections
      have occurred. Currently, only limited information on neutralization capacity
      variability of individual IVIG lots against the different echovirus serotypes is
      available. Infectivity assays were established for the most prevalent echovirus
      serotypes (E 9, E 11, E 13, and E 30) circulating in the United States (US) and
      the European Union (EU). The echovirus serotype-specific neutralization titers of
      41 IVIG lots manufactured from either whole blood (Recovered) or collected by
      apheresis (Source) and from either the US or EU, were determined. Significantly
      higher (P < 0.0001) neutralization titers against E 11 and E 30 were found in
      IVIG lots manufactured from US Source plasma compared to US Recovered plasma.
      Geographically, IVIG lots made from US plasma contained significantly (P <
      0.0001) higher neutralization titers against E 9 and E 11 than lots manufactured
      from EU plasma, whereas lots made from EU plasma showed significantly higher
      neutralization of E 30. To conclude, IVIG lots differ in their neutralizing
      antibody content against different echovirus serotypes, depending on plasma
      collection practices and geographic origin. Based on these results, an informed
      choice in selecting IVIG lots with the highest available neutralization titer
      against the specific echovirus serotype would seem to be beneficial during
      treatment of break-through infections.

PMID- 21181928
TI  - Soluble CD30: a serum marker for Epstein-Barr virus-associated
      lymphoproliferative diseases.
AB  - The soluble form of CD30 (sCD30), a member of tumor necrosis factor receptor
      superfamily, has been used as a marker of disease activity in various lymphomas.
      Epstein-Barr virus (EBV) is a potent stimulator of CD30 expression. The study
      aims to evaluate whether sCD30 can be used as a diagnostic marker for EBV
      associated infectious mononucleosis (IM) and post-transplant lymphoproliferative
      disease (PTLD). Plasma from EBV seropositive healthy controls (N = 90), acute IM
      patients (n = 90), non-PTLD heart/lung transplant recipients (N = 30) and EBV
      positive PTLD patients (N = 23) was tested for sCD30 using a commercially
      available ELISA kit. EBV DNA was tested by real time quantitative polymerase
      chain reaction assay. Significantly higher sCD30 levels were observed in acute IM
      patients (median 242.9 ng/ml) compared to EBV seropositive controls (median 15.7
      ng/ml; P < 0.0001). These levels were highest in IM patients within 14 days of
      onset of illness. PTLD patients had significantly higher sCD30 levels (median 94
      ng/ml) than healthy controls (P < 0.0001) and transplant patients (median 27
      ng/ml; P = 0.0007). EBV DNA was detected mostly in acute IM and PTLD patients. In
      both cases there was a significant correlation between sCD30 and EBV DNA levels
      in plasma (P < 0.0001). This study demonstrates that sCD30 and EBV DNA levels can
      be used as potential markers for diagnosis of IM and PTLD.

PMID- 21181929
TI  - Epstein-barr virus in diffuse large B-Cell lymphoma in immunocompetent patients
      in Japan is as low as in Western Countries.
AB  - According to previous reports, the frequency of Epstein-Barr virus (EBV)
      positivity in diffuse large B-cell lymphoma is higher in East Asia (approximately
      9%) than in Western countries. The presence of the EBV genome was examined in
      diffuse large B-cell lymphoma patients registered with the Osaka Lymphoma Study
      Group (OLSG) in Osaka, Japan, situated in East Asia. The EBV-positive rate was
      examined with in situ hybridization (ISH) in 484 immunocompetent diffuse large B
      cell lymphoma patients registered with OLSG. The male-to-female ratio was 1.29,
      with ages ranging from 16 to 95 (median, 68) years. ISH with EBV-encoded small
      RNAs (EBER) probes revealed positive signals in the nuclei of tumor cells: the
      frequency of positively stained cells among all tumor cells was almost none in
      458 cases, 5-10% in 5, 10-20% in 5, 20-50% in 11, and >50% in 5. When the
      frequency was >20% or >50%, the EBV-positive rate in the present series (3.3% or
      1.0%) was rather similar to that reported in Western cases. Careful evaluation of
      patient backgrounds, including age distribution, type of lymphomas, exclusion of
      immunocompromised patients, and establishment of definite criteria for EBV
      positivity (>20%, >50%, or almost all tumor cells) are essential in comparing
      geographical differences.

PMID- 21181930
TI  - A novel real-time PCR system for simultaneous detection of human viruses in
      clinical samples from patients with uncertain diagnoses.
AB  - A novel simultaneous detection system for human viruses was developed using a
      real-time polymerase chain reaction (PCR) system to identify causes of infection
      in clinical samples from patients with uncertain diagnoses. This system,
      designated as the "multivirus real-time PCR," has the potential to detect 163
      human viruses (47 DNA viruses and 116 RNA viruses) in a 96-well plate
      simultaneously. The specificity and sensitivity of each probe-primer set were
      confirmed with cells or tissues infected with specific viruses. The multivirus
      real-time PCR system showed profiles of virus infection in 20 autopsies of
      acquired immunodeficiency syndrome patients, and detected frequently TT virus,
      cytomegalovirus, human herpesvirus 6, and Epstein-Barr virus in various organs;
      however, RNA viruses were detected rarely except for human immunodeficiency virus
      1. Pathology samples from 40 patients with uncertain diagnoses were examined,
      including cases of encephalitis, hepatitis, and myocarditis. Herpes simplex virus
      1, human herpesvirus 6, and parechovirus 3 were identified as causes of diseases
      in four cases of encephalitis, while no viruses were identified in other cases as
      causing disease. This multivirus real-time PCR system can be useful for detecting
      virus in specimens from patients with uncertain diagnoses.

PMID- 21181931
TI  - Detection of human parechovirus in stool samples collected from children with
      acute gastroenteritis in Japan during 2007-2008.
AB  - Of 477 stool specimens, which had been screened for rotavirus, adenovirus,
      norovirus, sapovirus and astrovirus, collected from infants and children with
      acute gastroenteritis in pediatric clinics encompassing five localities (Sapporo,
      Tokyo, Maizuru, Osaka, and Saga) in Japan from July 2007 to June 2008, 247
      negative samples (51.7%) were subjected to screening for human parechovirus.
      Human parechovirus (HPeV) was detected by RT-PCR using a primer pair to amplify
      5'UTR region of its genome and was genotyped by sequencing of the VP1 gene. HPeV
      was detected in 20 of 247 specimens tested, and the detection rate was found to
      be 8.1%. Seventeen of the 20 strains that tested positive for HPeV were sequenced
      successfully the VP1 gene. The majority of the HPeV strains (n = 15) could be
      identified as HPeV1, and the remaining 2 strains could be typed as HPeV3. By
      phylogenetic and identical matrix analyses of HPeV VP1 sequences, HPeV1 should be
      divided into two lineages, and all of the Japanese studied HPeV1 strains belong
      to the lineage 2 accordingly. This is the first report of the circulation of
      HPeV, especially HPeV1 in Japan.

PMID- 21181932
TI  - Molecular epidemiology of human respiratory syncytial virus subgroups A and B
      identified in adults with hematological malignancy attending an Irish hospital
      between 2004 and 2009.
AB  - Human respiratory syncytial virus (HRSV) is an important cause of respiratory
      infection in patients with hematological malignancy, particularly hematopoietic
      stem cell transplant recipients. This study investigated the genetic variability
      of the attachment (G) protein gene among HRSV isolates collected from adult
      patients with hematological malignancy. Between December 2004 and March 2009, 60
      samples collected from 58 adults attending an Irish hospital were positive for
      HRSV by direct immunofluorescence. Nucleotide sequence analysis of the G gene
      showed a slightly higher frequency of HRSV subgroup A (52%) than HRSV subgroup B
      (48%). Genetic variability was higher among subgroup A viruses (up to 13% at
      nucleotide level) than among subgroup B viruses (up to 4%). Phylogenetic analysis
      revealed two genotypes of HRSV subgroup A, GA2 and GA5, which cocirculated
      between 2004/2005 and 2007/2008, although GA2 alone was identified in season
      2008/2009. Genotype BA was the only genotype of HRSV subgroup B identified.
      Genotype-specific amino acid substitutions were identified, with two and seven
      changes for GA2 and GA5, respectively. Furthermore, one to four potential N
      glycosylation sites were found among HRSV subgroup A isolates while two to three
      were identified in HRSV B isolates. Predicted O-glycosylation sites included 25
      34 and 40-43 in HRSV subgroups A and B, respectively. The average synonymous
      mutation-to-non-synonymous mutation ratios (dS/dN) implied neutral selection
      pressure on both HRSV subgroup isolates. This study provides data for the first
      time on the molecular epidemiology of HRSV isolates over five successive epidemic
      seasons among patients attending an Irish hospital.

PMID- 21181933
TI  - Genetic characterization of Bulgarian rotavirus isolates and detection of
      rotavirus variants: challenges for the rotavirus vaccine program?
AB  - Annually 20-70% of all hospital admissions and 20% of fatal diarrhea cases among
      children less than 5 years of age occur due to severe rotavirus diarrhea.
      Universal immunization is the major strategy aimed at controlling rotavirus
      infection. The main objective of the present study was to elucidate the
      evolutionary relationships of the most common rotavirus strains co-circulating in
      Bulgaria. The sequence and phylogenetic analysis revealed strain diversity and
      circulation of different rotavirus variants belonging to a single genotype. A
      mutated G4P[8] strain with the insertion of an asparagine residue in position 76;
      G2, G9, and G1 variants with amino acid substitutions in the antigenic regions A,
      B, and/or C were all identified in this study in the absence of an immunization
      program. Rotavirus strain surveillance in both the pre- and post-vaccine eras is
      of increasing importance in order to assess the effectiveness of the rotavirus
      vaccines for protection against disease associated with a diverse population of
      rotavirus strains.

PMID- 21181934
TI  - VP7 Gene of human rotavirus A genotype G5: Phylogenetic analysis reveals the
      existence of three different lineages worldwide.
AB  - Group A rotavirus (RV-A) genotype G5, which is common in pigs, was also detected
      in children with severe diarrhea in Brazil, Argentina, Paraguay, Cameroon, China,
      Thailand, and Vietnam. To evaluate the evolutionary relationship among RV-A G5
      strains, the VP7 and VP4 genes of 28 Brazilian RV-A G5 human strains, sampled
      between 1986 and 2005, were sequenced and compared with other RV-A G5 strains
      currently circulating worldwide in animals and humans. The phylogenetic analysis
      of RV-A G5 VP7 gene strains demonstrates the existence of three main lineages:
      (a) Lineage I: Brazilian strains grouped with three porcine strains from
      Thailand; (b) Lineage II: porcine, bovine, and equine strains from different
      regions; (c) Lineage III: human strains isolated in Asia and Africa, and two
      porcine strains from Argentina. The VP8* (*non-typable) subunit of VP4 gene
      sequencing showed that all P[8] strains fell into three major genetic lineages:
      P[8]-1; P[8]-2; and P[8]-3. These results showed that the RV-A G5 strains
      circulating in humans are the result of two independent zoonotic transmission
      events, most likely from pigs.

PMID- 21181935
TI  - Full genomic analysis of a G8P[1] rotavirus strain isolated from an asymptomatic
      infant in Kenya provides evidence for an artiodactyl-to-human interspecies
      transmission event.
AB  - Group A rotavirus (GAR) G8P[1] strains, found sometimes in cattle, have been
      reported rarely from humans. Therefore, analysis of the full genomes of human
      G8P[1] strains are of significance in the context of studies on interspecies
      transmission of rotaviruses. However, to date, only partial-length nucleotide
      sequences are available for the 11 genes of a single human G8P[1] strain, while
      the partial sequences of two other strains have been reported. The present study
      reports the first complete genome sequence of a human G8P[1] strain, B12,
      detected from an asymptomatic infant in Kenya in 1987. By nucleotide sequence
      identities and phylogenetic analyses, the full-length nucleotide sequences of VP7
      VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5 genes of strain B12 were assigned to
      G8-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3 genotypes, respectively. Each of the 11 genes
      of strain B12 appeared to be more related to cognate genes of artiodactyl
      (ruminant and/or camelid) and/or artiodactyl-derived human GAR strains than those
      of most other rotaviruses. Strain B12 exhibited low levels of genetic relatedness
      to canonical human GAR strains, such as Wa and DS-1, ruling out the possibility
      of its origin from reassortment events between artiodactyl-like human and true
      human strains. These observations suggest that strain B12 might have been
      directly transmitted from artiodactyls to humans. Unhygienic conditions and close
      proximity of humans to livestock at the sampling site might have facilitated this
      rare event. This is the first report on a full genomic analysis of a rotavirus
      strain from Kenya. To our knowledge, strain B12 might be the oldest G8 strain
      characterized molecularly from the Africa continent.

PMID- 21181939
TI  - Hemodynamic patterning of the avian atrioventricular valve.
AB  - In this study, we develop an innovative approach to rigorously quantify the
      evolving hemodynamic environment of the atrioventricular (AV) canal of avian
      embryos. Ultrasound generated velocity profiles were imported into Micro-Computed
      Tomography generated anatomically precise cardiac geometries between Hamburger
      Hamilton (HH) stages 17 and 30. Computational fluid dynamic simulations were then
      conducted and iterated until results mimicked in vivo observations. Blood flow in
      tubular hearts (HH17) was laminar with parallel streamlines, but strong vortices
      developed simultaneous with expansion of the cushions and septal walls. For all
      investigated stages, highest wall shear stresses (WSS) are localized to AV canal
      valve-forming regions. Peak WSS increased from 19.34 dynes/cm(2) at HH17 to
      287.18 dynes/cm(2) at HH30, but spatiotemporally averaged WSS became 3.62
      dynes/cm(2) for HH17 to 9.11 dynes/cm(2) for HH30. Hemodynamic changes often
      preceded and correlated with morphological changes. These results establish a
      quantitative baseline supporting future hemodynamic analyses and interpretations.

PMID- 21181940
TI  - FilaminB is required for the directed localization of cell-cell adhesion
      molecules in embryonic epithelial development.
AB  - Filamin proteins cross-link F-actin and form a scaffold for numerous signal
      transduction systems. In this study, we show that filaminB is apically enriched
      in avian embryonic epithelium, and colocalizes with cell adhesion molecules and
      circumferential F-actin. FilaminB knockdown in the neural tube and somites
      decreases the accumulation of N-cadherin and ZO-1 protein at cell junctions, and
      promotes disruption of these tissues and the presence of neuronal aggregates
      within the lumen of the neural tube. This phenotype resembles that of human
      congenital condition, periventricular heterotopia (PH). FilaminB knockdown in
      MDCK cells suggests that filaminB is required for the apical accumulation of
      adhesion molecules in the junctional complex and subsequent epithelium formation.
      We further suggest that the reduction of structural integrity of the neural
      epithelium caused by the loss of Filamin function may also result in formation of
      the neuronal nodules found in PH patients.

PMID- 21181941
TI  - Embryonic development of the emu, Dromaius novaehollandiae.
AB  - The chick, Gallus gallus, is the traditional model in avian developmental
      studies. Data on other bird species are scarce. Here, we present a comparative
      study of the embryonic development of the chick and the emu Dromaius
      novaehollandiae, a member of Paleognathae, which also includes the ostrich, rhea,
      tinamou, kiwi, and cassowary. Emu embryos ranging from Hamburger and Hamilton
      (HH) equivalent stages 1 to 43 were collected and their gross morphology
      analyzed. Its early development was studied in detail with time-lapse imaging and
      molecular techniques. Emu embryos in general take 2-3 times longer incubation
      time to reach equivalent chicken stages, requiring 1 day for HH2, 2.5 days for
      HH4, 7 days for limb bud initiation, 23 days for feather germ appearance, and
      approximately 50-56 days for hatching. Chordin gene expression is similar in emu
      and chick embryos, and emu Brachyury is not expressed until HH3. Circulation is
      established at approximately the 27- to 30-somite stage. Forelimb buds are formed
      and patterned initially, but their growth is severely retarded. The size
      difference between an emu and a chick embryo only becomes apparent after limb bud
      formation. Overall, emu and chick embryogenesis proceeds through similar stages,
      but developmental heterochrony between these two species is widely observed.

PMID- 21181943
TI  - The dynamic gene expression patterns of transcription factors constituting the
      sea urchin aboral ectoderm gene regulatory network.
AB  - The temporal and spatial expression patterns of regulatory genes are required for
      building a gene regulatory network (GRN). The current ectoderm GRN model for the
      sea urchin embryo includes pregastrular specification functions in the oral (OE)
      and aboral ectoderm (AE). Unlike the OE, which is resolved into several
      subdomains, the AE is considered a simpler territory due to the lack of detailed
      gene expression studies in this territory. Here, we perform temporal and spatial
      gene expression studies on the eight transcription factor genes constituting the
      AE GRN. Based on the differential gene expression patterns, we conclude that the
      AE contains at least three subdomains at the mesenchyme blastula stage. We also
      performed immunostaining for pSmad1/5/8 to monitor the activation of the BMP
      signaling pathway. The dynamic changes in the expression patterns of these
      transcription factor genes and the nuclearization of pSmad1/5/8 may provide a
      foundation for resolving the AE GRN.

PMID- 21181942
TI  - Long form of latent TGF-beta binding protein 1 (Ltbp1L) regulates cardiac valve
      development.
AB  - Transforming Growth Factor beta (TGF-beta) is crucial for valve development and
      homeostasis. The long form of Latent TGF-beta binding protein 1 (LTBP1L)
      covalently binds all TGF-beta isoforms and regulates their bioavailability.
      Ltbp1L expression analysis during valvulogenesis revealed two patterns of Ltbp1L
      production: an early one (E9.5-11.5) associated with endothelial-to-mesenchymal
      transformation (EMT); and a late one (E12.5 to birth) contemporaneous with valve
      remodeling. Similarly, histological analysis of Ltbp1L(-/-) developing valves
      identified two different pathologies: generation of hypoplastic endocardial
      cushions in early valvulogenesis, followed by development of hyperplastic valves
      in late valvulogenesis. Ltbp1L promotes valve EMT, as Ltbp1L absence yields
      hypoplastic endocardial cushions in vivo and attenuated EMT in vitro. Ltbp1L(-/-)
      valve hyperplasia in late valvuogenesis represents a consequence of prolonged
      EMT. We demonstrate that Ltbp1L is a major regulator of Tgf-beta activity during
      valvulogenesis since its absence results in a perturbed Tgf-beta pathway that
      causes all Ltbp1L(-/-) valvular defects.

PMID- 21181944
TI  - beta8 integrin and band 4.1B cooperatively regulate morphogenesis of the
      embryonic heart.
AB  - Morphogenesis of the heart is regulated by various cues, including growth factors
      and extracellular matrix (ECM) proteins. The mechanisms by which cardiac cells
      properly integrate these cues to regulate growth, differentiation, and migration
      remain poorly understood. Here we have used genetic strategies in mice to
      identify alphavbeta8 integrin and its cytoskeletal adaptor protein, Band 4.1B, as
      essential regulators of cardiac morphogenesis. We demonstrate that approximately
      60% of mouse embryos genetically null for beta8 integrin and Band 4.1B display
      cardiovascular phenotypes and die by E11.5. This premature death is due, in part,
      to defective development of the cardiac outflow tract (OFT), with reduced
      expression of smooth muscle alpha-actin (SMAalpha-actin) in OFT cells derived
      from the cardiac neural crest. These data are the first to identify cell adhesion
      and signaling pathways regulated by alphavbeta8 integrin and Band 4.1B as
      essential for normal formation and function of the heart during embryogenesis.

PMID- 21181945
TI  - Identification and expression patterns of members of the protease-activated
      receptor (PAR) gene family during zebrafish development.
AB  - Protease-activated receptors (PARs) play critical roles in hemostasis in
      vertebrates including zebrafish. However, the zebrafish gene classification
      appears to be complex, and the expression patterns of par genes are not
      established. Based on analyses of genomic organization, phylogenetics, protein
      primary structure, and protein internalization, we report the identification of
      four zebrafish PARs: par1, par2a, par2b, and par3. This classification differs
      from one reported previously. We also show that these genes have distinct
      spatiotemporal expression profiles in embryos and larvae, with par1, par2a, and
      par2b expressed maternally and ubiquitously during gastrula stages and their
      expression patterns refined at later stages, and par3 expressed only in 3-day-old
      larvae. Notably, the expression patterns of zebrafish par1 and par2b resemble
      those of their mammalian counterparts, suggesting that receptor function is
      conserved among vertebrates. This conservation is supported by our findings that
      Par1 and Par2b are internalized following exposure to thrombin and trypsin,
      respectively.

PMID- 21181946
TI  - A chemical enterocolitis model in zebrafish larvae that is dependent on
      microbiota and responsive to pharmacological agents.
AB  - Inflammatory bowel disease (IBD) results from dysfunctional interactions between
      the intestinal immune system and microbiota, influenced by host genetic
      susceptibility. Because a key feature of the pathology is intestinal epithelial
      damage, potential disease factors have been traditionally analyzed within the
      background of chemical colitis models in mice. The zebrafish has greatly
      complemented the mouse for modeling aspects of disease processes, with an
      advantage for high content drug screens. Larval zebrafish exposed to the
      haptenizing agent trinitrobenzene sulfonic acid (TNBS) displayed impaired
      intestinal homeostasis and inflammation reminiscent of human IBD. There was a
      marked induction of pro-inflammatory cytokines, the degradative enzyme mmp9 and
      leukocytosis. Enterocolitis was dependent on microbiota and Toll-like receptor
      signaling, that can be ameliorated by antibiotic and anti-inflammatory drug
      treatments. This system will be useful to rapidly interrogate in vivo the
      biological significance of the IBD candidate genes so far identified and to carry
      out pharmacological modifier screens.

PMID- 21181954
TI  - Multiple myeloma: 2011 update on diagnosis, risk-stratification, and management.
AB  - DISEASE OVERVIEW: Multiple myeloma is malignant plasma-cell disorder that
      accounts for ~10% of all hematologic malignancies. DIAGNOSIS: The diagnosis
      requires (1) 10% or more clonal plasma cells on bone marrow examination or a
      biopsy-proven plasmacytoma plus (2) evidence of end-organ damage felt to be
      related to the underlying plasma cell disorder. RISK STRATIFICATION: Patients
      with 17p deletion, t(4;14), t(14;16), t(14;20), and karyotypic deletion 13 or
      hypodiploidy are considered to have high-risk myeloma. All others are considered
      to have standard-risk disease. RISK-ADAPTED THERAPY: Standard-risk patients are
      treated with nonalkylator-based therapy such as lenalidomide plus low-dose
      dexamethasone (Rd) followed by autologous stem-cell transplantation (ASCT). If
      patients are tolerating the induction regimen treatment well, an alternative
      strategy is to continue initial therapy after stem-cell collection, reserving
      ASCT for first relapse. High-risk patients are treated with a bortezomib-based
      induction followed by ASCT and then bortezomib-based maintenance. Patients not
      eligible for ASCT can be treated with Rd for standard risk disease or a
      bortezomib-based regimen if high-risk features are present. To reduce toxicity,
      when using bortezomib, the once-weekly dose is preferred; similarly, when using
      dexamethasone, the low-dose approach (40 mg once a week) is preferred, unless
      there is a need for rapid disease control. MANAGEMENT OF REFRACTORY DISEASE:
      Patients with indolent relapse can be treated first with lenalidomide,
      bortezomib, or alkylators plus low-dose corticosteroids. Patients with more
      aggressive relapse often require therapy with a combination of multiple active
      agents. The most promising new agents in development are pomalidomide and
      carfilizomib.

PMID- 21181955
TI  - Myelophthisis in breast cancer.

PMID- 21181958
TI  - An International Urogynecological Association (IUGA)/International Continence
      Society (ICS) joint terminology and classification of the complications related
      directly to the insertion of prostheses (meshes, implants, tapes) and grafts in
      female pelvic floor surgery.
AB  - INTRODUCTION AND HYPOTHESIS: A terminology and standardized classification has
      yet to be developed for those complications arising directly from the insertion
      of synthetic (prostheses) and biological (grafts) materials in female pelvic
      floor surgery. METHODS: This report on the above terminology and classification
      combines the input of members of the Standardization and Terminology Committees
      of two International Organizations, the International Urogynecological
      Association (IUGA) and the International Continence Society (ICS) and a Joint
      IUGA/ICS Working Group on Complications Terminology, assisted at intervals by
      many expert external referees. An extensive process of 11 rounds of internal and
      external review took place with exhaustive examination of each aspect of the
      terminology and classification. Decision-making was by collective opinion
      (consensus). RESULTS: A terminology and classification of complications related
      directly to the insertion of prostheses and grafts in female pelvic floor surgery
      has been developed, with the classification based on category (C), time (T) and
      site (S) classes and divisions, that should encompass all conceivable scenarios
      for describing insertion complications and healing abnormalities. The CTS code
      for each complication, involving three (or four) letters and three numerals, is
      likely to be very suitable for any surgical audit or registry, particularly one
      that is procedure-specific. Users of the classification have been assisted by
      case examples, colour charts and online aids (www.icsoffice.org/complication).
      CONCLUSION: A consensus-based terminology and classification report for
      prosthesis and grafts complications in female pelvic floor surgery has been
      produced, aimed at being a significant aid to clinical practice and research.

PMID- 21181959
TI  - What was hot at the joint ICS and IUGA meeting Toronto, Canada, 23-27 August
      2010.

PMID- 21181961
TI  - Evaluating the use of different waveforms for intravesical electrical
      stimulation: a study in the rat.
AB  - AIM: For decades, monophasic square wave pulses have been used for intravesical
      electrical stimulation (IVES) in diagnosis and treatment of lower urinary tract
      dysfunction. The use of other waveforms, more preferred by patients or more
      effective for neural stimulation, has hardly been studied before. This study
      compares the effect of several waveforms and derived parameters in IVES. METHODS:
      IVES, performed in eight female Sprague-Dawley rats, was given for 300 sec with
      constant frequency (10 Hz) and current amplitude (6 mA) with unipolar square,
      biphasic square, asymmetric biphasic square, double square, unipolar exponential
      rise, biphasic exponential rise, and double-exponential rise wavepulses with
      different pulse durations (2 * 5 msec, 20 msec, or 2 * 20 msec). Bladder pressure
      was recorded. Average current and average power were calculated. RESULTS:
      Stimulations with the different waveforms resulted in the same maximal pressure
      rise (all P>0.1). The average charge was zero for biphasic waveforms. For
      exponential rise pulse waveforms the total injected charge was lower than that
      for the monophasic square pulse waveform. The average power was the highest for
      biphasic waveforms and the lowest for monophasic double-exponential rise pulses
      waveform. CONCLUSIONS: Charge-balanced waveforms, which are more preferred by
      patients, are equally effective in evoking IVES-induced detrusor contraction as
      monophasic square pulse waveforms. Thus, it can be beneficial in clinical
      practice to replace the monophasic square pulse waveform for IVES by charge
      balanced waveforms. Furthermore, the stimulation power and thus the requested
      energy can be reduced by changing the waveform. This can be important for
      electrical stimulation using implanted batteries.

PMID- 21181960
TI  - Mixed incontinence: comparing definitions in non-surgical patients.
AB  - PURPOSE: We aimed to explore operational definitions of mixed urinary
      incontinence (MUI) for use in incontinence outcomes research for non-surgical
      patient populations. METHODS: A secondary analysis of women with urge
      incontinence or urge predominant MUI enrolled in the Urinary Incontinence
      Treatment Network BE-DRI randomized clinical trial was performed. Subjects were
      characterized at baseline for urinary incontinence severity and incontinence
      subtype (stress or urge) using the Medical, Epidemiologic, and Social Aspects of
      Aging (MESA) questionnaire, the Urogenital Distress Inventory, and a 7-day
      urinary diary. Various different definitions of MUI, ranging from low to high
      threshold, were created using a combination of these baseline incontinence
      measures. Prevalence of MUI based on each definition was described and compared
      to treatment response. Logistic regression analysis was used to estimate the
      association between the study outcomes and the different definitions of MUI.
      RESULTS: The 307 participants in the BE-DRI study had a mean age of 56.9 (+/-
      13.9) years with a mean total MESA score of 21.7 (+/- 8.9) and a mean total UDI
      score of 120.5 (+/- 49.6). The proportion of women diagnosed with MUI varied
      significantly by definition ranging from 63.5% to 96.4%. Low threshold symptom
      based definitions resulted in nearly universal diagnosis of MUI. No strict cut
      off value for these baseline measures was identified to predict clinical
      outcomes. CONCLUSIONS: Current MUI definitions do not adequately categorize
      clinically relevant UI subgroups. For research purposes we believe it necessary
      to describe the severity of each incontinence subtype separately in subjects with
      MUI.

PMID- 21181963
TI  - Controlling motion sickness and spatial disorientation and enhancing vestibular
      rehabilitation with a user-worn see-through display.
AB  - OBJECTIVES/HYPOTHESES: An eyewear mounted visual display ("User-worn see-through
      display") projecting an artificial horizon aligned with the user's head and body
      position in space can prevent or lessen motion sickness in susceptible
      individuals when in a motion provocative environment as well as aid patients
      undergoing vestibular rehabilitation. In this project, a wearable display device,
      including software technology and hardware, was developed and a phase I
      feasibility study and phase II clinical trial for safety and efficacy were
      performed. STUDY DESIGN: Both phase I and phase II were prospective studies
      funded by the NIH. The phase II study used repeated measures for motion
      intolerant subjects and a randomized control group (display device/no display
      device) pre-posttest design for patients in vestibular rehabilitation. METHODS:
      Following technology and display device development, 75 patients were evaluated
      by test and rating scales in the phase II study; 25 subjects with motion
      intolerance used the technology in the display device in provocative environments
      and completed subjective rating scales, whereas 50 patients were evaluated before
      and after vestibular rehabilitation (25 using the display device and 25 in a
      control group) using established test measures. RESULTS: All patients with motion
      intolerance rated the technology as helpful for nine symptoms assessed, and 96%
      rated the display device as simple and easy to use. Duration of symptoms
      significantly decreased with use of the technology displayed. In patients
      undergoing vestibular rehabilitation, there were no significant differences in
      amount of change from pre- to posttherapy on objective balance tests between
      display device users and controls. However, those using the technology required
      significantly fewer rehabilitation sessions to achieve those outcomes than the
      control group. CONCLUSIONS: A user-worn see-through display, utilizing a visual
      fixation target coupled with a stable artificial horizon and aligned with user
      movement, has demonstrated substantial benefit for individuals susceptible to
      motion intolerance and spatial disorientation and those undergoing vestibular
      rehabilitation. The technology developed has applications in any environment
      where motion sensitivity affects human performance.

PMID- 21181966
TI  - Quality and appropriateness of care: the response to allegations and actions
      needed by the cardiovascular professional.

PMID- 21181967
TI  - Sirolimus- versus paclitaxel-eluting stents for unselected patients with coronary
      artery disease.

PMID- 21181968
TI  - Clinical observation, logical thinking, probability modeling, and the limitations
      imposed by closed and integrated human biology.

PMID- 21181969
TI  - Nevo stent: a successful stent makeover.

PMID- 21181970
TI  - William Tell's arrow and the entrapment of catheters by a vascular closure
      device.

PMID- 21181971
TI  - Troubleshooting and treating the balloon that fails to deflate.

PMID- 21181972
TI  - Transcatheter closure of perimembranous VSD: symmetric and asymmetric occluders.

PMID- 21181973
TI  - Takotsubo cardiomyopathy and microvascular dysfunction: another diagnostic
      criteria or predisposing factor?

PMID- 21181974
TI  - The Slauson cutoff and peri-operative risk for abdominal vascular surgery.

PMID- 21181975
TI  - Percutaneous mechanical thrombectomy in patients with submassive pulmonary
      embolism: an Underutilized and Understudied Tool!

PMID- 21181977
TI  - Atresiaplasty versus BAHA for congenital aural atresia.

PMID- 21181978
TI  - Can radiologic imaging replace second-look procedures for cholesteatoma?

PMID- 21181979
TI  - Is partial tonsillectomy equivalent to total tonsillectomy for obstructive
      symptoms?

PMID- 21181980
TI  - How necessary are postoperative debridements after endoscopic sinus surgery?1.

PMID- 21181981
TI  - Transorbital endoscopic repair of cerebrospinal fluid leaks.
AB  - OBJECTIVES: To describe an anatomic and clinical outcome study of transorbital
      neuroendoscopic surgical (TONES) for the repair of complex anterior cranial fossa
      (ACF) cerebrospinal fluid (CSF) leaks. DESIGN: Anatomic cadaver investigation and
      clinical outcomes evaluation. METHODS: An anatomic cadaver study was undertaken
      to determine the anatomic feasibility of the TONES approaches for repair of CSF
      leaks, and determine the optimal approaches for these repairs. A targeted outcome
      analysis was performed on 10 consecutive patients who underwent 12 ACF CSF leak
      repairs by TONES. RESULTS: The cadaver study demonstrated that the entire ACF can
      be accessed by TONES. Due to the rise and angulation of the orbital roof above
      the interorbital ACF, the precaruncular (PC) approach optimal for a coplanar
      target approach in the interorbital ACF, and the superior lid crease (SLC)
      trajectory is preferable for procedures involving the supraorbital ACF. There
      were no complications in the 12 clinical procedures. Fifty percent of the cases
      were revisions, referred after up to five previous craniotomies and endoscopic
      procedures; all TONES repairs were successful with a single operation.
      CONCLUSIONS: The use of TONES to repair ACF CSF leaks was demonstrated to be
      technically feasible in cadaver and clinical studies. The SLC approach was
      optimal for supraorbital ACF leaks; the PC approach was preferable for
      interorbital ACF pathology. TONES was shown to be highly effective for treating
      complex pathology that was refractory to correction through frontal craniotomy
      and /or transnasal endoscopy, providing safe, minimally disruptive direct
      coplanar routes for target approach and manipulation.

PMID- 21181982
TI  - Endoscopic endonasal dissection of the infratemporal fossa: Anatomic
      relationships and importance of eustachian tube in the endoscopic skull base
      surgery.
AB  - OBJECTIVES: Endoscopic endonasal approaches to the pterygopalatine and
      infratemporal fossae are technically challenging due to the complex anatomy of
      these areas. This project attempts to develop an anatomic and surgical model to
      enhance the understanding of these spaces from the endonasal endoscopic
      perspective. METHODS: Eight pterygopalatine and infratemporal fossae were
      dissected in four adult human specimens in accordance with institutional
      protocols. All specimens were prepared with vascular injections using colored
      latex. Both the pterygopalatine and infratemporal fossae were accessed using a
      transpterygoid approach, which included a medial maxillectomy. Rod lens
      endoscopes (with 0 degrees , 30 degrees , and 45 degrees  lenses), surgical
      microscope, microsurgical and endoscopic instruments were used to complete the
      dissections. RESULTS: Endoscopic endonasal approaches provided adequate access to
      the pterygopalatine and infratemporal fossae. Dissection of the internal
      maxillary artery and its terminal branches, and detachment of the medial and
      lateral pterygoid muscles were critical steps to access deeper structures of the
      infratemporal fossa. The lateral pterygoid plate was the most useful landmark to
      locate foramen ovale, and the mandibular branch of the trigeminal nerve. The
      Eustachian tube, medial pterygoid plate, and styloid process were the most useful
      landmarks to locate parapharyngeal poststyloid structures (parapharyngeal segment
      of the internal carotid artery, internal jugular vein, cranial nerves IX and X).
      CONCLUSIONS: A medial maxillectomy coupled with a transpterygoid endoscopic
      approach, provides adequate access to the pterygopalatine and infratemporal
      fossae. The complex anatomy of the infratemporal fossa requires precise
      identification of surgical landmarks to assure preservation of neurovascular
      structures.

PMID- 21181983
TI  - Impact of surgeon and hospital volume on short-term outcomes and cost of
      laryngeal cancer surgical care.
AB  - OBJECTIVE: To evaluate the impact of surgeon and hospital case volume and other
      related variables on short-term outcomes after surgery for laryngeal cancer.
      METHODS: The Maryland Health Service Cost Review Commission database was queried
      for laryngeal cancer surgical case volumes from 1990 to 2009. Multivariate
      logistic regression analyses and multiple linear regression models were used to
      evaluate for significant associations between surgeon and hospital case volume,
      as well as other independent variables and the risk of in-hospital death,
      postoperative wound complications, length of hospital stay, and hospital-related
      cost of care. RESULTS: Overall, 1,981 laryngeal cancer surgeries were performed
      with complete financial data available for 1,885 laryngeal cancer surgeries,
      performed by 284 surgeons at 37 hospitals. The only independently significant
      factor associated with the risk of in-hospital death was an APR-DRG mortality
      risk score of 4 (odds ratio [OR] = 10.7, P < .001). Postoperative wound fistula
      or dehiscence was associated with an increased mortality risk score (OR = 3.1, P
      < .001), total laryngectomy (OR = 12.4, P = .013), and flap reconstruction (OR =
      3.8, P = .001). Increased mortality risk score, partial or total laryngectomy,
      flap reconstruction, and Black race were associated with an increased length of
      stay and hospital-related costs. After controlling for all other variables, a
      statistically significant negative correlation was observed between surgery at a
      high-volume hospital and both length of hospital stay (geometric mean = -1.5
      days, P = .003). and hospital-related costs (geometric mean = -$6,061, P = .003).
      CONCLUSIONS: After controlling for other factors, high-volume hospital care is
      associated with a shorter length of hospitalization and lower hospital-related
      cost of care for laryngeal cancer surgery.

PMID- 21181984
TI  - Arytenoid dislocation: An analysis of the contemporary literature.
AB  - OBJECTIVES/HYPOTHESIS: To discuss the incidence, diagnosis, laryngeal findings,
      and management of arytenoid dislocation as a separate entity from vocal fold
      paralysis. STUDY DESIGN: Literature review. METHODS: A contemporary review of the
      literature was performed by searching the terms arytenoid cartilage dislocation
      and subluxation in various combinations. Articles were analyzed and selected
      based on relevance and content. RESULTS: Arytenoid dislocation is described as an
      uncommon laryngeal finding associated with intubation or blunt laryngeal trauma.
      The majority of recent publications are case reports or small case series.
      Diagnosis of arytenoid dislocation with flexible laryngoscopy, helical computed
      tomography, videostroboscopy, and laryngeal electromyography is recommended. In
      most reported cases, diagnosis has been made based on the position of the
      arytenoid at laryngoscopy. Reduction and repositioning of the arytenoid cartilage
      is reported with limited success noted with delayed diagnosis. Speech therapy may
      also be a beneficial treatment option. CONCLUSIONS: Although arytenoid
      dislocation is reported in the literature, the body of available evidence fails
      to sufficiently differentiate it as a separate entity from unilateral vocal fold
      paralysis. Flexible laryngoscopy is inadequate as a standalone procedure to
      distinguish arytenoid dislocation from laryngeal nerve injury.

PMID- 21181985
TI  - The assessment of olivocochlear function in neonates with real-time distortion
      product otoacoustic emissions.
AB  - OBJECTIVES/HYPOTHESIS: Otoacoustic emissions (OAE) can be suppressed with
      activation of the medial olivocochlear neural pathway by stimulation of the
      contralateral ear. The primary objective of this study was to assess the
      feasibility of using olivocochlear mediated OAE suppression to test neonatal
      hearing with a novel device that detects changes in distortion product (DP)OAE
      level with high temporal resolution. The secondary objective was to investigate
      whether temporal parameters of the response can be determined with this technique
      and used in the assessment of neonates at risk of auditory neuropathy spectrum
      disorder (ANSD). STUDY DESIGN: Prospective translational study of novel hearing
      assessment technique. METHODS: There were 46 neonates tested in a clinic or
      neonatal intensive care unit (NICU). DPOAE were recorded in real time with narrow
      band pass digital filtering (1 ms temporal resolution) during presentation of an
      intermittent contralateral broadband noise stimulus. Magnitude and latency of the
      contralateral suppression response were compared with hearing outcome (auditory
      brainstem response screen and clinical follow-up) and risk factors for hearing
      loss, particularly hyperbilirubinemia as a risk factor for ANSD. RESULTS: :
      Contralateral suppression was identified in all of 38 neonates with detectable
      DPOAE and normal hearing, most reliably at f(2) = 4.4 kHz (average values = 1 dB
      suppression from DP level of 14 dB SPL using 0.55 s contralateral stimulus at 50
      dB SPL). Sensorineural hearing loss was identified in three cases (6.5%) and ANSD
      in five cases (11% of all neonates tested). Contralateral suppression was absent
      in two of the ANSD cases (one associated with cochlear nerve aplasia, the other
      with hyperbilirubinemia) and present in three. The median latency for onset of
      contralateral suppression was 60 ms and offset latency 83 ms. The latency for
      offset of suppression was longer in neonates who required treatment for
      hyperbilirubinemia at 123 ms (P = .02, Mann-Whitney rank sum test). Latency
      measurements were determined with high intraobserver reliability (Pearson product
      moment correlation coefficient > 0.96). CONCLUSIONS: Contralateral suppression of
      real-time DPOAE can reliably be identified in neonates. This is likely a
      manifestation of olivocochlear activity, although middle ear muscle reflexes
      might contribute to suppression in some circumstances. The technique provides a
      feasible objective test of hearing in neonates that can be applied in the NICU
      setting without sedation. The presence of a response indicates detection of sound
      by the contralateral ear and effective brainstem transmission of neural signals,
      therefore providing a more sensitive test of hearing than OAE alone. The high
      temporal resolution of the technique allows measurement of latency of the
      response. These benefits help to identify neonates at risk of ANSD and have the
      potential to provide prognostic information that will assist in the management of
      this unpredictable disorder. Further development of the technique is indicated
      with regard to determination of hearing threshold, frequency specific testing,
      and automation of response detection.

PMID- 21182023
TI  - Commensal gut flora reduces susceptibility to experimentally induced colitis via
      T-cell-derived interleukin-10.
AB  - BACKGROUND: Regulatory cytokines are well known to modify experimental colitis in
      mice. The aim of this study was to elucidate the effect of interleukin (IL)-10
      derived from different cellular sources and the effect of commensal gut flora in
      dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: Wildtype (WT) and
      IL-10 deficient (IL-10(-/-) ) mice either harboring a characterized specific
      pathogen-free (SPF) gut flora or germfree were exposed to 2% DSS. Moreover, cell
      type-specific IL-10, IL-4, and IL-12 knockout mice and animals combining the T
      cell-specific IL-10 knockout with a deficiency in IL-12 or IL-4 were exposed to
      DSS. RESULTS: SPF IL-10(-/-) mice showed an increased susceptibility to DSS
      induced colitis compared to WT mice determined by histopathology and
      proinflammatory cytokine and chemokine responses. Under germfree conditions, both
      WT and IL-10(-/-) mice were highly susceptible to DSS. IL-10 mRNA was increased
      upon DSS exposure in WT SPF but not in germfree mice. Mice carrying a specific
      deletion of IL-10 in T-cells exhibited a tendency towards an enhanced
      susceptibility to DSS. The lack of T-cell-derived IL-10 in combination with the
      lack of IL-4 increased the susceptibility to DSS colitis, as did the lack of IL
      12 alone. CONCLUSIONS: IL-10 is a crucial factor inhibiting the innate
      proinflammatory immune response induced by DSS. Intestinal bacteria are necessary
      for the induction of protective IL-10, which is mainly T-cell-derived. T-cell
      derived IL-10 can only mediate its protective effect in a Th1-dominated milieu.
      If the balance is shifted towards a Th2 response, IL-10 is not protective.

PMID- 21182036
TI  - Advances in endovascular repair for complex aneurysms.

PMID- 21182037
TI  - Laparoscopic rectal cancer surgery.

PMID- 21182041
TI  - Evidence-based review of enhancing postoperative recovery after breast surgery
      (Br J Surg 2011; 98: 181-196).

PMID- 21182047
TI  - Functional outcomes after extended surgery for gastric cancer (Br J Surg 2011;
      98: 239-245).

PMID- 21182057
TI  - Systematic review and meta-analysis of laparoscopic Nissen (posterior total)
      versus Toupet (posterior partial) fundoplication for gastro-oesophageal reflux
      disease (Br J Surg 2010; 97: 1318-1330).

PMID- 21182060
TI  - Percutaneous transhepatic biliary drainage catheter tract recurrence in
      cholangiocarcinoma (Br J Surg 2010; 97: 1860-1866).

PMID- 21182061
TI  - Short-term outcomes with intrathecal versus epidural analgesia in laparoscopic
      colorectal surgery (Br J Surg 2010; 97: 1401-1406).

PMID- 21182064
TI  - Closure of the LAPSIS trial (Br J Surg 2010; 97: 1598).

PMID- 21182070
TI  - Robert Koch prizes: honouring researchers in immunology and infectious diseases.

PMID- 21182071
TI  - Contrasting models for the roles of Aire in the differentiation program of
      epithelial cells in the thymic medulla.
AB  - The current prevailing view regarding the role of Aire in self-tolerance is that
      it is involved in the transcriptional control of many tissue-restricted self
      antigen genes in thymic epithelial cells in the medulla (mTECs); however,
      accumulating evidence also suggests that Aire has other roles, e.g. in mTEC
      differentiation, and furthermore that Aire can either promote or inhibit the mTEC
      differentiation program, i.e. Aire does not play a neutral role in mTEC
      differentiation. This review discusses when and how Aire plays an important role
      in controlling the organization of mTECs required for the expression of self
      antigen genes.

PMID- 21182072
TI  - Guiding the "misguided" - functional conditioning of dendritic cells for the DC
      based immunotherapy against tumours.
AB  - The concept of DC-based tumour vaccine has been tested both clinically and
      experimentally for the past two decades. Even though only limited success has
      been achieved to date, DC vaccination remains a promising immunological approach
      against tumours and deserves further exploration. It aims to elicit and establish
      specific immunity to destroy tumours. By such an approach, DC are used not only
      as a vector to deliver tumour antigens, but also as a "natural adjuvant" to boost
      vaccine efficacy. Tumours are however of mutated "self", to which the host immune
      system is essentially tolerated in the absence of external perturbation
      otherwise. Such a live cell-based approach is unfortunately extremely sensitive
      to, hence its efficacy inevitably limited by, the tumour microenvironment.
      Certain immunosuppressive mechanisms triggered by the tumour cells are therefore
      major obstacles against successful DC vaccination. Attempts have since been made
      in order to overcome these hurdles. This brief review summarises some of the
      earlier and current findings, and compares the effectiveness of various
      approaches used in these studies. It focuses particularly on strategies aimed at
      enhancing DC immunogenicity, through molecular modifications and functional
      conditioning of the cell vectors, targeting both the positive and negative
      regulators of DC functions. By dissecting the roles of DC in immunity versus
      tolerance induction, and the very mechanisms underlying autoimmunity, we examine
      further and try to explain how the suppressed or "misguided" immunity may be
      alternatively switched-on and more effectively redirected for cancer therapy.

PMID- 21182073
TI  - gammadelta T cells develop, respond and survive - with a little help from CD27.
AB  - Although the TNF receptor family member CD27 has been known for some time, its
      functional role as a coreceptor on T and B cells remains poorly understood.
      Recent reports have shown that CD27 and its ligand CD70 play a critical role in
      the development and function of gammadelta T cells in mice. In this issue of the
      European Journal of Immunology, a study now extends these findings to the
      Vgamma9Vdelta2(+) subset of human gammadelta T cells. This subset, whose
      responses are readily elicited by phosphoantigens, plays an important role in
      anti-tumor immune responses. This study shows that most Vgamma9Vdelta2(+) cells
      express CD27, and signaling via the CD27-CD70 axis is needed for their survival,
      proliferation and cytokine secretion. Moreover, CD27 functions as a coreceptor,
      which promotes, in conjunction with TCR-mediated signals, expansion of Th1-biased
      Vgamma9Vdelta2(+) cells. This new information underscores the significance of
      CD27 in gammadelta T-cell functional differentiation, and is likely to facilitate
      the development of gammadelta T-cell-based clinical immunotherapy.

PMID- 21182075
TI  - Differences in the production of spliced antigenic peptides by the standard
      proteasome and the immunoproteasome.
AB  - Peptide splicing allows the production of antigenic peptides composed of two
      fragments initially non-contiguous in the parental protein. The proposed
      mechanism of splicing is a transpeptidation occurring within the proteasome.
      Three spliced peptides, derived from FGF-5, melanoma protein gp100 and nuclear
      protein SP110, have been described. Here, we compared the production of these
      spliced peptides by the standard proteasome and the immunoproteasome.
      Differential isotope labelling was used to quantify (by mass spectrometry) the
      fragments contained in digests obtained with precursor peptides and purified
      proteasomes. The results show that both the standard and the immunoproteasomes
      can produce spliced peptides although they differ in their efficiency of
      production of each peptide. The FGF-5 and gp100 peptides are more efficiently
      produced by the standard proteasome, whereas the SP110 peptide is more
      efficiently produced by the immunoproteasome. This seems to result from
      differences in the production of the two splicing partners, which depends on a
      balance between cleavages liberating or destroying those fragments. By showing
      that splicing depends on the efficiency of production of the splicing partners,
      these results also support the transpeptidation model of peptide splicing.
      Furthermore, given the presence of immunoproteasomes in dendritic cells and cells
      exposed to IFN-gamma, the findings may be relevant for vaccine design.

PMID- 21182074
TI  - TLR5 functions as an endocytic receptor to enhance flagellin-specific adaptive
      immunity.
AB  - Innate immune activation via TLR induces dendritic cell maturation and secretion
      of inflammatory mediators, generating favorable conditions for naive T-cell
      activation. Here, we demonstrate a previously unknown function for TLR5, namely
      that it enhances MHC class-II presentation of flagellin epitopes to CD4(+) T
      cells and is required for induction of robust flagellin-specific adaptive immune
      responses. Flagellin-specific CD4(+) T cells expanded poorly in TLR5-deficient
      mice immunized with flagellin, a deficiency that persisted even when additional
      TLR agonists were provided. Flagellin-specific IgG responses were similarly
      depressed in the absence of TLR5. In marked contrast, TLR5-deficient mice
      developed robust flagellin-specific T-cell responses when immunized with
      processed flagellin peptide. Surprisingly, the adaptor molecule Myd88 was not
      required for robust CD4(+) T-cell responses to flagellin, indicating that TLR5
      enhances flagellin-specific CD4(+) T-cell responses in the absence of
      conventional TLR signaling. A requirement for TLR5 in generating flagellin
      specific CD4(+) T-cell activation was also observed when using an in vitro
      dendritic cell culture system. Together, these data uncover an Myd88-independent
      function for dendritic cell TLR5 in enhancing the presentation of peptides to
      flagellin-specific CD4(+) T cells.

PMID- 21182076
TI  - IL-27 increases the proliferation and effector functions of human naive CD8+ T
      lymphocytes and promotes their development into Tc1 cells.
AB  - IL-27 has been shown to exhibit both pro- and anti-inflammatory properties; it
      favors mouse naive CD4(+) T-cell differentiation into Th1 cells to the detriment
      of Th17 and Th2 skewing and regulates IL-10 and IL-17 production by human CD4(+)
      T cells. Moreover, IL-27 promotes proliferation and cytotoxic functions of mouse
      CD8(+) T lymphocytes, but no data are available on human CD8(+) T cells. We
      investigated the impact of IL-27 on human CD8(+) T cells. In contrast to mouse T
      cells, the IL-27 receptor (IL-27R), composed of T cell cytokine receptor (TCCR)
      and gp130, was detected on a greater percentage of human CD8(+) than CD4(+) T
      cells and these proportions increased upon polyclonal activation. IL-27 induced
      rapid STAT1 and STAT3 signaling, enhanced STAT1 protein levels, and induced SOCS1
      and SOCS3 expression in a STAT1-dependent manner by human CD8(+) T cells.
      Addition of IL-27 to alpha-CD3-activated naive CD8(+) T cells significantly
      increased T-box transcription factor expression levels, cell proliferation, and
      IFN-gamma and granzyme B production leading to increased CD8(+) T-cell-mediated
      cytotoxicity. These results demonstrate that IL-27, a rapidly produced cytokine
      by activated APC, has a profound impact on human naive CD8(+) T cells, driving
      them to become highly efficient Tc1 cells.

PMID- 21182077
TI  - T-bet-mediated differentiation of the activated CD8+ T cell.
AB  - The T-box transcription factor, T-bet promotes the differentiation of short-lived
      effector CD8(+) T cells at the expense of central memory cells. How T-bet
      mediates these effects, and whether they are directly caused by T-bet alone are
      unknown, because expression of T-bet requires stimulation of the T cell by
      inflammatory and growth cytokines, which may have T-bet-independent functions
      involving T-cell differentiation. We developed an in vitro system of ectopic T
      bet expression that avoids the effects of inflammatory cytokines to determine
      which aspects of the T-bet phenotype may be accounted for by T-bet alone. Ectopic
      T-bet expression by OT-I CD8(+) T cells stimulated by the H2-Kb (SIINFEKL)
      complex and cultured with 2 ng/mL IL-2 induced a coordinated change in gene
      expression leading to down-regulation of CD127 and SOCS-1 and up-regulation of
      CD122 and IL-15 receptor alpha, switching the cellular survival cytokine from IL
      7 to IL-15. T-bet expression and 2 ng/mL IL-2 also led to a capacity for IFN
      gamma and Fas ligand expression, confirming a role in eliciting these effector
      functions. Finally, ectopic T-bet promoted the expression of B lymphocyte-induced
      maturation protein 1 by OT-I cells in the presence of 20 ng/mL IL-2, providing a
      mechanism for the role of T-bet in driving terminal differentiation in concert
      with a high level of IL-2 receptor signalling.

PMID- 21182078
TI  - Galectin-9 ameliorates acute GVH disease through the induction of T-cell
      apoptosis.
AB  - Galectins comprise a family of animal lectins that differ in their affinity for
      beta-galactosides. Galectin-9 (Gal-9) is a tandem-repeat-type galectin that was
      recently shown to function as a ligand for T-cell immunoglobin domain and mucin
      domain-3 (Tim-3) expressed on terminally differentiated CD4(+) Th1 cells. Gal-9
      modulates immune reactions, including the induction of apoptosis in Th1 cells. In
      this study, we investigated the effects of Gal-9 in murine models of acute GVH
      disease (aGVHD). First, we demonstrated that recombinant human Gal-9 inhibit MLR
      in a dose-dependent manner, involving both Ca(2+) influx and apoptosis in T
      cells. Next, we revealed that recombinant human Gal-9 significantly inhibit the
      progression of aGVHD in murine BM transplantation models. In conclusion, Gal-9
      ameliorates aGVHD, possibly by inducing T-cell apoptosis, suggesting that gal-9
      may be an attractive candidate for the treatment of aGVHD.

PMID- 21182079
TI  - Rhoh deficiency reduces peripheral T-cell function and attenuates allogenic
      transplant rejection.
AB  - Rhoh is a hematopoietic system-specific GTPase. Rhoh-deficient T cells have been
      shown to have a defect in TCR signaling manifested during their thymic
      development. Our aims were to investigate the phenotype of peripheral Rhoh
      deficient T cells and to explore in vivo the potential benefit of Rhoh deficiency
      in a clinically relevant situation, in which T-cell inhibition is desirable. In
      murine allogenic kidney transplantation, Rhoh deficiency caused a significant 75%
      reduction of acute and chronic transplant rejection accompanied by 75% lower
      alloantigen-specific antibody levels and significantly better graft function.
      This effect was independent of the lower T-cell numbers in Rhoh-deficient
      recipients, because injection of equal numbers of Rhoh-deficient or control T
      cells into kidney transplanted mice with SCID led again to a significant 60%
      reduction of rejection. Mixed lymphocyte reaction revealed that the weaker
      alloreactivity was associated with a 85% lower cytotoxicity and a 50-80% lower
      cytokine release in Rhoh-deficient T cells without an influence on the secretion
      itself. Antigen uptake and presentation in DC were unaffected by Rhoh deficiency.
      These findings stress the importance of Rhoh for the function of peripheral T
      cells.

PMID- 21182080
TI  - Tertiary lymphoid organs in renal allografts can be associated with donor
      specific tolerance rather than rejection.
AB  - Tertiary lymphoid organs can form at sites of chronic inflammation. Their
      presence has been mainly associated with tissue destruction. In transplantation,
      there is a dynamic immune response as in chronic inflammation. Indeed, the
      presence of tertiary lymphoid organs has been associated with chronic rejection.
      In addition to a destructive alloimmune response, secondary lymphoid organs are
      also important in transplant tolerance. We hypothesised that tertiary lymphoid
      organs may also form during transplantation tolerance as this process also
      requires an active local immune response. If so, their presence may enhance
      tolerance, resulting in better graft function rather than chronic rejection.
      Using a mouse kidney allograft model of tolerance, we demonstrate the formation
      of tertiary lymphoid organs within tolerated allografts. Tertiary lymphoid organs
      are supplied by high endothelial venules, and contain T and B cells, macrophages,
      DC, Foxp3(+) T cells, donor MHC class II(+) cells and recipient cells presenting
      donor-derived allopeptides. Formation of tertiary lymphoid organs and the
      presence of immune cells within them are associated with superior graft function,
      suggesting that tertiary lymphoid organs act to amplify the prevailing immune
      response, be it a tolerant and beneficial immune response or the previously
      described destructive alloimmunity.

PMID- 21182081
TI  - Selection of escape mutant by HLA-C-restricted HIV-1 Pol-specific cytotoxic T
      lymphocytes carrying strong ability to suppress HIV-1 replication.
AB  - HIV-1 mutants escaping from HLA-A- or HLA-B-restricted CTL have been well
      studied, but those from HLA-C-restricted CTL have not. Therefore we investigated
      the ability of HLA-C-restricted CTL to select HIV-1 escape mutants. In the
      present study, we identified two novel HLA-Cw(*) 1202-restricted Pol-specific CTL
      epitopes (Pol328-9 and Pol463-10). CTL specific for these epitopes were detected
      in 25-40% of chronically HIV-1-infected HLA-Cw(*) 1202(+) individuals and had
      strong abilities to kill HIV-1-infected cells and to suppress HIV-1 replication
      in vitro, suggesting that these CTL may have the ability to effectively control
      HIV-1 in some HLA-Cw(*) 1202(+) individuals. Sequence analysis of these epitopes
      showed that a V-to-A substitution at the 9th position (V9A) of Pol 463-10 was
      significantly associated with the HLA-Cw(*) 1202 allele and that the V9A mutant
      was slowly selected in the HLA-Cw(*) 1202(+) individuals. Pol 463-10-specific CTL
      failed both to kill the V9A virus-infected cells and to suppress replication of
      the V9A mutant. These results indicate that the V9A mutation was selected as an
      escape mutant by the Pol463-10-specific CTL. The present study strongly suggests
      that some HLA-C-restricted CTL have a strong ability to suppress HIV-1
      replication so that they can select HIV escape mutants as in the case of HLA-A
      restricted or HLA-B-restricted CTL.

PMID- 21182082
TI  - CD4+ T-cell immunity to the Burkholderia pseudomallei ABC transporter LolC in
      melioidosis.
AB  - Burkholderia pseudomallei causes melioidosis, a disease with a wide range of
      possible outcomes, from seroconversion and dormancy to sepsis and death. This
      spectrum of host-pathogen interactions poses challenging questions about the
      heterogeneity in immunity to B. pseudomallei. Models show protection to be
      dependent on CD4(+) cells and IFN-gamma, but little is known about specific
      target antigens. Having previously implicated the ABC transporter, LolC, in
      protective immunity, we here use epitope prediction, HLA-binding studies, HLA
      transgenic models and studies of T cells from seropositive individuals to
      characterize HLA-restricted LolC responses. Immunized mice showed long-lasting
      memory to the protein, whereas predictive algorithms identified epitopes within
      LolC that subsequently demonstrated strong HLA class II binding. Immunization of
      HLA-DR transgenics with LolC stimulated T-cell responses to four of these
      epitopes. Furthermore, the responsiveness of HLA transgenics to LolC revealed a
      hierarchy supportive of HLA polymorphism-determined differential susceptibility.
      Seropositive human donors of diverse HLA class II types showed T-cell responses
      to LolC epitopes, which are conserved among Burkholderia species including
      Burkholderia cenocepacia, associated with life-threatening cepacia complex in
      cystic fibrosis patients and Burkholderia mallei, which causes glanders. These
      findings suggest a role for LolC epitopes in multiepitope vaccine design for
      melioidosis and related diseases.

PMID- 21182083
TI  - Cystatin cures visceral leishmaniasis by NF-kappaB-mediated proinflammatory
      response through co-ordination of TLR/MyD88 signaling with p105-Tpl2-ERK pathway.
AB  - Cystatin could completely cure experimental visceral leishmaniasis by switching
      the differentiation of Th2 cells to Th1 type, as well as upregulating NO, and
      activation of NF-kappaB played a major role in these processes. Analysis of
      upstream signaling events revealed that TLR 2/4-mediated MyD88-dependent
      participation of IL-1R-activated kinase (IRAK)1, TNF receptor-associated factor
      (TRAF)6 and TGFbeta-activated kinase (TAK)1 is essential to induce cystatin
      mediated IkappaB kinase (IKK)/NF-kappaB activation in macrophages. Cystatin plus
      IFN-gamma activated the IKK complex to induce phosphorylation-mediated
      degradation of p105, the physiological partner and inhibitor of the MEK kinase,
      tumor progression locus 2 (Tpl-2). Consequently, Tpl-2 was liberated from p105,
      thereby stimulating activation of the MEK/ERK MAPK cascade. Cystatin plus IFN
      gamma-induced IKK-beta post-transcriptionally modified p65/RelA subunit of NF
      kappaB by dual phosphorylation in infected phagocytic cells. IKK induced the
      phosphorylation of p65 directly on Ser-536 residue whereas phosphorylation on Ser
      276 residue was by sequential activation of Tpl-2/MEK/ERK/MSK1. Collectively, the
      present study indicates that cystatin plus IFN-gamma-induced MyD88 signaling may
      bifurcate at the level of IKK, leading to a divergent pathway regulating NF
      kappaB activation by IkappaBalpha phosphorylation and by p65 transactivation
      through Tpl-2/MEK/ERK/MSK1.

PMID- 21182084
TI  - Generation of human Th1-like regulatory CD4+ T cells by an intrinsic IFN-gamma-
      and T-bet-dependent pathway.
AB  - Murine Foxp3(+) Treg have recently been shown to express T-bet, a transcription
      factor characteristic of Th1 effector cells. A human Treg phenotype equivalent
      has not been reported. Here, we show that naive human CD4(+) T cells incubated
      with low numbers of CD40-activated allogeneic B cells preferentially
      differentiate into alloantigen-specific CD4(hi) CD25(hi) Treg. These
      differentiated cells potently suppress effector T-cell responses and express T
      bet, IFN-gamma, and CXCR3, the features of Th1 effector cells. In contrast, co
      culture of naive CD4(+) T cells with high numbers of allogeneic B cells results
      in CD4(+) CD25(+) T cells that promote, rather than inhibit, effector T-cell
      responses, demonstrating the plasticity of CD4(+) T-cell differentiation in
      response to alloantigen-presenting B cells. The optimal accumulation of CD4(hi)
      CD25(hi) Treg induced using higher T cell:B cell co-culture ratios was dependent
      on the expression of T-bet and endogenously produced IFN-gamma. Induction of Treg
      mediated suppression function in the Treg population was not. As CXCR3 confers
      the preferential trafficking of T cells to tissue sites of IFN-gamma, these human
      Th1-like Treg might be useful for modulating pathological Th1 effector responses,
      such as that occurring during graft-versus-host disease or graft rejection.

PMID- 21182086
TI  - Measles virus modulates dendritic cell/T-cell communication at the level of
      plexinA1/neuropilin-1 recruitment and activity.
AB  - Measles virus (MV)-infected DC fail to promote T-cell expansion, and this could
      explain important aspects of measles immunosuppression. The efficiency of the
      immune synapse (IS) is determined by the formation of stable, stimulatory
      conjugates involving a spatially and timely controlled architecture. PlexinA1
      (plexA1) and its co-receptor neuropilin (NP-1) have been implicated in IS
      efficiency, while their repulsive ligand, SEMA3A, likely acts in terminating T
      cell activation. Conjugates involving MV-infected DC and T cells are unstable and
      not stimulatory, and thus we addressed the potential role of plexA1/NP-1 and
      semaphorins (SEMAs) in this system. MV does not grossly affect expression levels
      of plexA1/NP-1 on T cells or DC, yet prevents their recruitment towards
      stimulatory interfaces. Moreover, MV infection promoted early release of SEMA3A
      from DC, which caused loss of actin based protrusions on T cells as did the
      plexA4 ligand SEMA6A. SEMA3A/6A differentially modulated chemokinetic migration
      of T cells and conjugation with allogeneic DC. Thus, MV targets SEMA receptor
      function both at the level of IS recruitment, and by promoting a timely
      inappropriate release of their repulsive ligand, SEMA3A. To the best of our
      knowledge, this is the first example of viral targeting of SEMA receptor function
      in the IS.

PMID- 21182085
TI  - Estrogen receptor-beta ligand treatment modulates dendritic cells in the target
      organ during autoimmune demyelinating disease.
AB  - Estrogens act upon nuclear estrogen receptors (ER) to ameliorate cell-mediated
      autoimmune disease. As most immunomodulatory effects of estrogens in EAE have
      been attributed to the function of ER-alpha, we previously demonstrated that ER
      beta ligand treatment reduced disease severity without affecting peripheral
      cytokine production or levels of CNS inflammation, suggesting a direct
      neuroprotective effect; however, the effect of ER-beta treatment on the function
      of immune cells within the target organ remained unknown. Here, we used adoptive
      transfer studies to show that ER-beta ligand treatment was protective in the
      effector, but not the induction phase of EAE, as shown by decreased clinical
      disease severity with the preservation of axons and myelin in spinal cords. The
      analysis of the immune cell infiltrates in the CNS revealed that while ER-beta
      ligand treatment did not reduce overall levels of CNS inflammation, there was a
      decrease in the DC percentage, and these CNS DC had decreased TNF-alpha
      production. Finally, experiments using DC deficient in ER-beta revealed that the
      expression of ER-beta on DC was essential for protective effects of ER-beta
      ligand treatment in EAE. Our results demonstrate for the first time an effect of
      ER-beta ligand treatment in vivo on DC in the target organ of a prototypic cell
      mediated autoimmune disease.

PMID- 21182087
TI  - TNF superfamily member 13, APRIL, inhibits allergic lung inflammation.
AB  - The T-cell functions of a proliferation-inducing ligand (APRIL, also known as
      TNFSF13) remain largely undefined. We previously showed that APRIL suppressed Th2
      cytokine production in cultured CD4(+) T cells and Th2 antibody responses. Here
      we show that APRIL suppresses allergic lung inflammation, which is associated
      with diminished expression of the transcription factor c-maf. Mice deficient in
      the April gene (April(-/-) mice) had significantly aggravated lung inflammation
      compared with WT mice in the ovalbumin-induced allergic lung inflammation model.
      Likewise, blockade of APRIL in WT mice by the APRIL-receptor fusion protein,
      transmembrane activator and calcium modulator and cyclophilin ligand interactor
      (TACI)-Ig, enhanced lung inflammation. Transfer of APRIL-sufficient, ovalbumin
      specific, TCR-transgenic CD4(+) T (OT-II) cells to April(-/-) mice restored the
      suppressive effect of APRIL on lung inflammation. Mechanistically, the expression
      of the Th2 cytokine transcription factor c-maf, but not GATA-3, was markedly
      enhanced in April(-/-) CD4(+) T cells at the RNA and protein level and under non
      polarizing (Th neutral, ThN) and Th2-polarizing conditions. Since c-maf
      transactivates the IL-4 gene, the increased c-maf expression in April(-/-) mice
      readily explains increased Th2 cytokine production. Independent of its effect on
      IL-4, APRIL suppressed IL-13 expression. APRIL thus may regulate lung
      inflammation in a dual way, by acting on c-maf expression and by directly
      controlling IL-13 production.

PMID- 21182088
TI  - Borrelia species induce inflammasome activation and IL-17 production through a
      caspase-1-dependent mechanism.
AB  - Borrelia burgdorferi spirochetes cause Lyme disease, which can result in severe
      clinical symptoms such as multiple joint inflammation and neurological disorders.
      IFN-gamma and IL-17 have been suggested to play an important role in the host
      defense against Borrelia, and in the immunopathology of Lyme disease. The caspase
      1-dependent cytokine IL-1beta has been linked to the generation of IL-17
      producing T cells, whereas caspase-1-mediated IL-18 is crucial for IFN-gamma
      production. In this study, we show by using knockout mice the role of
      inflammasome-activated caspase-1 in the regulation of cytokine responses by B.
      burgdorferi. Caspase-1-deficient cells showed significantly less IFN-gamma and IL
      17 production after Borrelia stimulation. A lack of IL-1beta was responsible for
      the defective IL-17 production, whereas IL-18 was crucial for the IFN-gamma
      production. Caspase-1-dependent IL-33 played no role in the Borrelia-induced
      production of IL-1beta, IFN-gamma or IL-17. In conclusion, we describe for the
      first time the role of the inflammasome-dependent caspase-1 activation of
      cytokines in the regulation of IL-17 production induced by Borrelia spp. As IL-17
      has been implicated in the pathogenesis of chronic Lyme disease, these data
      suggest that caspase-1 targeting may represent a new immunomodulatory strategy
      for the treatment of complications of late stage Lyme disease.

PMID- 21182089
TI  - Negative regulation of Toll-like receptor signaling plays an essential role in
      homeostasis of the intestine.
AB  - A healthy intestinal tract is characterized by controlled homeostasis due to the
      balanced interaction between commensal bacteria and the host mucosal immune
      system. Human and animal model studies have supported the hypothesis that
      breakdown of this homeostasis may underlie the pathogenesis of inflammatory bowel
      diseases. However, it is not well understood how intestinal microflora stimulate
      the intestinal mucosal immune system and how such activation is regulated. Using
      a spontaneous, commensal bacteria-dependent colitis model in IL-10-deficient
      mice, we investigated the role of TLR and their negative regulation in intestinal
      homeostasis. In addition to IL-10(-/-) MyD88(-/-) mice, IL-10(-/-) TLR4(-/-) mice
      exhibited reduced colitis compared to IL-10(-/-) mice, indicating that TLR4
      signaling plays an important role in inducing colitis. Interestingly, the
      expression of IRAK-M, a negative regulator of TLR signaling, is dependent on
      intestinal commensal flora, as IRAK-M expression was reduced in mice re-derived
      into a germ-free environment, and introduction of commensal bacteria into germ
      free mice induced IRAK-M expression. IL-10(-/-) IRAK-M(-/-) mice exhibited
      exacerbated colitis with increased inflammatory cytokine gene expression.
      Therefore, this study indicates that intestinal microflora stimulate the
      colitogenic immune system through TLR and negative regulation of TLR signaling is
      essential in maintaining intestinal homeostasis.

PMID- 21182090
TI  - CD70-CD27 interactions provide survival and proliferative signals that regulate T
      cell receptor-driven activation of human gammadelta peripheral blood lymphocytes.
AB  - Human Vgamma9Vdelta2 T cells are potent anti-tumor lymphocytes that specifically
      respond to pyrophosphate (phospho-) antigens, which constitute the basis of
      current gammadelta T-cell-based immunotherapy strategies. Despite a clear
      involvement of the TCR, the costimulation requirements of Vgamma9Vdelta2 T cells
      remain ill-defined. Here, we show that the expression of the CD27 receptor by the
      vast majority of Vgamma9Vdelta2 peripheral blood lymphocytes endows them with
      enhanced proliferative capacity upon ligation by its unique ligand CD70, a tumor
      necrosis factor superfamily member expressed on lymphoma B-cells but also on TCR
      activated gammadelta T cells. Moreover, Vgamma9Vdelta2 T-cell treatment with
      soluble recombinant CD70 induced calcium signals and increased transcription of
      anti-apoptotic Bcl2a1 and cell-cycle-promoting Cyclin D2 genes. We further
      demonstrate that the manipulation of CD70-CD27 interactions significantly
      impacted on Vgamma9Vdelta2 T-cell survival, proliferation and cytokine secretion,
      in both loss-of-function and gain-of-function experiments. Thus, CD27 coreceptor
      signals strongly promoted the expansion of Th1-biased, CD27(+) Vgamma9Vdelta2
      peripheral blood lymphocytes in the context of TCR-mediated stimulation with
      phosphoantigens. These data collectively establish a novel role for the CD70-CD27
      axis in human gammadelta T-cell activation and hence open new perspectives for
      its modulation in clinical settings.

PMID- 21182091
TI  - Overexpression of phospholipase Cepsilon in keratinocytes upregulates cytokine
      expression and causes dermatitis with acanthosis and T-cell infiltration.
AB  - Phospholipase Cepsilon (PLCepsilon) is an effector of Ras and Rap small GTPases.
      We showed previously using PLCepsilon-deficient mice that PLCepsilon plays a
      critical role in activation of cytokine production in non-immune skin cells in a
      variety of inflammatory reactions. For further investigation of its role in
      inflammation, we created transgenic mice overexpressing PLCepsilon in epidermal
      keratinocytes. The resulting transgenic mice spontaneously developed skin
      inflammation as characterized by formation of adherent silvery scales, excessive
      growth of keratinocytes, and aberrant infiltration of immune cells such as T
      cells and DC. Development of the skin symptoms correlated well with increased
      expression of factors implicated in human inflammatory skin diseases, such as IL
      23, in keratinocytes, and with the accumulation of CD4(+) T cells producing IL
      22, a potent inducer of keratinocyte proliferation. Intradermal injection of a
      blocking antibody against IL-23 as well as treatment with the immunosuppressant
      FK506 reversed these skin phenotypes, which was accompanied by suppression of the
      IL-22-producing T-cell infiltration. These results reveal a crucial role of
      PLCepsilon in the development of skin inflammation and suggest a mechanism in
      which PLCepsilon induces the production of cytokines including IL-23 from
      keratinocytes, leading to the activation of IL-22-producing T cells.

PMID- 21182092
TI  - Carbohydrate recognition and complement activation by rat ficolin-B.
AB  - Ficolins are innate immune components that bind to PAMPs and structures on
      apoptotic cells. Humans produce two serum forms (L- and H-ficolin) and a
      leukocyte-associated form (M-ficolin), whereas rodents and most other mammals
      produce ficolins-A and -B, orthologues of L- and M-ficolin, respectively. All
      three human ficolins, together with mouse and rat ficolin-A, associate with
      mannan-binding lectin-associated serine proteases (MASPs) and activate the lectin
      pathway of complement on PAMPs. By contrast, mouse ficolin-B does not bind MASPs
      and cannot activate complement. Because of these striking differences together
      with the lack of functional information for other ficolin-B orthologues, we have
      characterized rat ficolin-B, and compared its physical and biochemical properties
      with its serum counterpart. The data show that both rat ficolins have archetypal
      structures consisting of oligomers of a trimeric subunit. Ficolin-B recognized
      mainly sialyated sugars, characteristic of exogenous and endogenous ligands,
      whereas ficolin-A had a surprisingly narrow specificity, binding strongly to only
      one of 320 structures tested: an N-acetylated trisaccharide. Surprisingly, rat
      ficolin-B activated MASP-2 comparable to ficolin-A. Mutagenesis data reveal that
      lack of activity in mouse ficolin-B is probably caused by a single amino acid
      change in the putative MASP-binding site that blocks the ficolin-MASP
      interaction.

PMID- 21182093
TI  - Novel splice variants of human IKKepsilon negatively regulate IKKepsilon-induced
      IRF3 and NF-kB activation.
AB  - The inhibitor of kappaB kinase epsilon (IKKepsilon) is pivotal for an efficient
      innate immune response to viral infections and has been recognized as breast
      cancer oncogene. The antiviral function of IKKepsilon involves activation of the
      transcription factors IFN regulatory factor 3 (IRF3) and NF-kappaB, thus inducing
      the expression of type I IFN. Here, we have identified two novel splice variants
      of human IKKepsilon, designated IKKepsilon-sv1 and IKKepsilon-sv2, respectively.
      Interestingly, RT-PCR revealed quantitatively different isoform expression in
      PBMC from different individuals. Moreover, we found cell type- and stimulus
      specific protein expression of the various splice variants. Overexpression of
      full-length wt IKKepsilon (IKKepsilon-wt) leads to the activation of NF-kappaB-
      as well as IRF3-driven luciferase reporter genes. Although none of the splice
      variants activates IRF3, IKKepsilon-sv1 still activates NF-kappaB, whereas
      IKKepsilon-sv2 is also defective in NF-kappaB activation. Both splice variants
      form dimers with IKKepsilon-wt and inhibit IKKepsilon-wt-induced IRF3 signaling
      including the antiviral activity in a dominant-negative manner. The lack of IRF3
      activation is likely caused by the failure of the splice variants to interact
      with the adapter proteins TANK, NAP1, and/or SINTBAD. Taken together, our data
      suggest alternative splicing as a novel regulatory mechanism suitable to shift
      the balance between different functions of IKKepsilon.

PMID- 21182094
TI  - Increased IL-17A secretion in response to Candida albicans in autoimmune
      polyendocrine syndrome type 1 and its animal model.
AB  - Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune
      disease caused by mutations in the autoimmune regulator (AIRE) gene. Chronic
      mucocutaneous candidiasis, hypoparathyroidism and adrenal failure are hallmarks
      of the disease. The critical mechanisms causing chronic mucocutaneous candidiasis
      in APS-1 patients have not been identified although autoantibodies to cytokines
      are implicated in the pathogenesis. To investigate whether the Th reactivity to
      Candida albicans (C. albicans) and other stimuli was altered, we isolated PBMC
      from APS-1 patients and matched healthy controls. The Th17 pathway was
      upregulated in response to C. albicans in APS-1 patients, whereas the IL-22
      secretion was reduced. Autoantibodies against IL-22, IL-17A and IL-17F were
      detected in sera from APS-1 patients by immunoprecipitation. In addition, Aire
      deficient (Aire(0/0) ) mice were much more susceptible than Aire(+/+) mice to
      mucosal candidiasis and C. albicans-induced Th17- and Th1-cell responses were
      increased in Aire(0/0) mice. Thus an excessive IL-17A reactivity towards C.
      albicans was observed in APS-1 patients and Aire(0/0) mice.

PMID- 21182095
TI  - IL-17 production by gammadelta T cells is important for the antitumor effect of
      Mycobacterium bovis bacillus Calmette-Guerin treatment against bladder cancer.
AB  - Intravesical inoculation of Mycobacterium bovis bacillus Calmette-Guerin (BCG)
      has been used for the treatment of bladder cancer. Recent studies implied the
      requirement of neutrophil infiltration for the antitumor effect. In this study,
      we found that IL-17 was produced in the bladder after BCG treatment, preceding
      the infiltration of neutrophils. Neutrophils in the bladder after BCG treatment
      were reduced in IL-17-deficient mice, in which BCG-induced antitumor effect
      against intravesically inoculated bladder cancer was abolished. Notably, the
      level of IL-17 production and the number of neutrophils in BCG-treated bladder
      was reduced in gammadelta T-cell-deficient mice but not in CD4-depleted mice.
      Survival of bladder cancer-inoculated gammadelta T-cell-deficient mice was not
      improved by BCG treatment. These results suggest that IL-17-producing gammadelta
      T cells play a key role in the BCG-induced recruitment of neutrophils to the
      bladder, which is essential for the antitumor activity against bladder cancer.

PMID- 21182096
TI  - Contamination with recombinant IFN accounts for the unexpected stimulatory
      properties of commonly used IFN-blocking antibodies.

PMID- 21182097
TI  - Improved detection of latent Mycobacterium tuberculosis infection in HIV-1
      seropositive individuals using cultured cellular assays.

PMID- 21182099
TI  - Determination of acetamiprid residues in zucchini grown under greenhouse
      conditions: application to behavioral dynamics.
AB  - A simple analytical method was developed for the determination of acetamiprid
      residues in zucchini and zucchini leaves grown under greenhouse conditions using
      liquid chromatography. Residues were confirmed via tandem mass spectrometry in
      positive-ion electrospray ionization mode. The calibration curves were linear
      with correlation coefficients in excess of 0.999. The limits of detection and
      limits of quantification were 0.01 and 0.03 ug/g and 0.02 and 0.06 ug/g, for the
      zucchini and zucchini leaves, respectively. For validation purposes, recoveries
      studies were carried out at low and high levels, yielding recovery rates ranged
      from 85.7 to 92.2% in zucchini and from 90.5 to 101.9% in zucchini leaves, with a
      relative standard deviation of <12%. The results demonstrated that the pattern of
      acetamiprid dissipation followed pseudo first-order kinetics with a half-life of
      1.9 and 2.5 days, respectively. The residues in zucchini leaves were
      substantially higher than in the zucchini plant itself. No residues were detected
      at 7 days post-application. The results of this study suggest that acetamiprid is
      acceptable for application in/on zucchini under the recommended dosage
      conditions.

PMID- 21182100
TI  - Vision & strategy: Predictive ecotoxicology in the 21st century.

PMID- 21182101
TI  - Current husbandry of red pandas (Ailurus fulgens) in zoos.
AB  - The endangered red panda (Ailurus fulgens) is held in zoos worldwide. The aim of
      this study was to examine how red pandas are kept and managed in captivity and to
      compare it with the management guidelines. Sixty-nine zoos, mainly from Europe
      but also from North America and Australia/New Zealand, responded to our survey.
      The results revealed that in general zoos follow the management guidelines for
      most of the investigated issues. The average enclosure is almost four times
      larger than the minimum size recommended by the management guidelines, although
      seven zoos have smaller enclosures. About half the zoos do not follow the
      guidelines concerning visitor access and number of nest boxes. Other issues that
      may compromise animal welfare include proximity of neighboring carnivore species
      and placement of nest boxes.

PMID- 21182102
TI  - Charles Hall Turner: 1961-2010.

PMID- 21182105
TI  - Charts to assess fetal wellbeing.

PMID- 21182109
TI  - Virtual bronchoscopy in the fetus.

PMID- 21182112
TI  - On the shoulders of giants: Robert G. Edwards, Nobel Laureate.

PMID- 21182115
TI  - Glenohumeral joint instability.
AB  - Due to the configuration of its bony elements, the glenohumeral joint is the most
      mobile joint of the body, but also an inherently unstable articulation.
      Stabilization of the joint is linked to a complex balance between static and
      dynamic soft tissue stabilizers. Because of complex biomechanics, and the
      existence of numerous classifications and acronyms to describe shoulder
      instability lesions, this remains a daunting topic for most radiologists. In this
      article we provide a brief review of the anatomy of the glenohumeral joint, as
      well as the classifications and the pathogenesis of shoulder instability.
      Technical aspects related to the available imaging techniques (including computed
      tomography [CT] arthrography, magnetic resonance imaging [MRI], and MR
      arthrography) are reviewed. We then describe the imaging findings related to
      shoulder instability, focusing on those elements that are important to the
      clinician.

PMID- 21182116
TI  - Preliminary evidence of altered gray and white matter microstructural development
      in the frontal lobe of adolescents with attention-deficit hyperactivity disorder:
      a diffusional kurtosis imaging study.
AB  - PURPOSE: To investigate non-Gaussian water diffusion using diffusional kurtosis
      imaging (DKI) to assess age effects on gray matter (GM) and white matter (WM)
      microstructural changes in the prefrontal cortex (PFC) of adolescents with
      attention-deficit hyperactivity disorder (ADHD) compared to typically developing
      controls (TDC). MATERIALS AND METHODS: In this preliminary cross-sectional study,
      T1-weighted magnetization-prepared rapid gradient echo (MPRAGE) and DKI images
      were acquired at 3T from TDC (n = 13) and adolescents with ADHD (n = 12).
      Regression analysis of the PFC region of interest (ROI) was conducted. RESULTS:
      TDC show a significant kurtosis increase of WM microstructural complexity from 12
      to 18 years of age, particularly in the radial direction, whereas WM
      microstructure in ADHD is stagnant in both the axial and radial directions. In
      ADHD, GM microstructure also lacked a significant age-related increase in
      complexity as seen in TDC; only kurtosis measures were able to detect this
      difference. CONCLUSION: These findings support the prevailing theory that ADHD is
      a disorder affecting frontostriatal WM. Our study is the first to directly
      quantify an aberrant age-related trajectory in ADHD within GM microstructure,
      suggesting that the assessment of non-Gaussian directional diffusion using DKI
      provides more sensitive and complementary information about tissue
      microstructural changes than conventional diffusion imaging methods.

PMID- 21182117
TI  - Increased gray matter volume of left pars opercularis in male orchestral
      musicians correlate positively with years of musical performance.
AB  - PURPOSE: To compare manual volumetry of gray matter (GM) / white matter (WM) of
      Broca's area subparts: pars opercularis (POP) and pars triangularis (PTR) in both
      hemispheres between musicians and nonmusician, as it has been shown that these
      regions are crucial for musical abilities. A previous voxel-based morphometric
      (VBM) study conducted in our laboratory reported increased GM density in Broca's
      area of left hemisphere in male orchestral musicians. Functional segregation of
      POP/PTR justified separate volumetric analysis of these parts. MATERIALS AND
      METHODS: We used the same cohort for the VBM study. Manual morphometry
      (stereology) was used to compare volumes between 26/26 right-handed orchestral
      musicians/nonmusicians. RESULTS: As expected, musicians showed significantly
      increased GM volume in the Broca's area, specifically in the left POP. No
      significant results were detected in right POP, left/right PTR GM volumes, and WM
      volumes for all regions. Results were positively correlated with years of musical
      performance (r = 0.7, P = 0.0001). CONCLUSION: This result corroborates the VBM
      study and is in line with the hypothesis of critical involvement of POP in
      hearing-action integration being an integral component of frontoparietotemporal
      mirror neuron network. We hypothesize that increased size of musicians' left POP
      represent use-dependent structural adaptation in response to intensive audiomotor
      skill acquisition.

PMID- 21182118
TI  - Divergent neural processes specific to the acute and sustained phases of verum
      and SHAM acupuncture.
AB  - PURPOSE: To discuss which brain region potentially functioned and switched
      between the immediate and delayed response of acupuncture. MATERIALS AND METHODS:
      A nonrepeated event-related functional MRI (fMRI) design was used to investigate
      the spatial and temporal patterns of acupuncture effects induced by needling an
      acupoint ST36 (ACU) and a nonmeridian point (SHAM). The standard general linear
      model was used to detect the immediate neural responses of acupuncture. Graph
      theory analysis was used to characterize the functional integrated network of the
      acupuncture delayed effect. RESULTS: Acupuncture induced significant signal
      changes in the limbic/paralimbic areas, neocortical regions, brainstem, and
      cerebellum for immediate effect both in ACU and SHAM. Some of these brain regions
      showed strong functional connectivity for a delayed effect in ACU. Conjunction
      analysis showed that the insula played a critical role during the overall process
      of ACU. No overlapping brain regions were found in SHAM. CONCLUSION: The findings
      of this study suggested that the delayed effects may reflect a more significant
      characteristic underlying acupuncture. Given that the insula as a relay station
      switched between the immediate and delayed response, it suggested that divergent
      functional connectivity patterns may mediate the acupuncture-related effects for
      ACU and SHAM.

PMID- 21182120
TI  - 3 Tesla MRI detects accelerated hippocampal volume reduction in postmenopausal
      women.
AB  - PURPOSE: To clarify age-related structural changes specific to hippocampal volume
      by hierarchizing according to age, gender, and menopausal status. Many studies
      report the neuroprotective effects of estrogen and age-related brain volume
      changes; however, there are no studies regarding age-related change specific to
      hippocampal volume in terms of age, gender, and menopausal status. MATERIALS AND
      METHODS: T1-weighted MR images were obtained in 412 healthy adults divided into
      eight groups according to age and gender, to analyze brain volume change focusing
      on hippocampal volume. RESULTS: Voxel-based morphometry (VBM) revealed
      significantly smaller gray matter volume in the hippocampus bilaterally in
      females aged in their fifties (51 of 59 females were at menopause) compared with
      females in their forties (3 of 46 females were at menopause). No significant
      difference was found, however, between female groups in their fifties versus
      sixties, or sixties versus seventies; or between male groups in their forties
      versus fifties, fifties versus sixties, or sixties versus seventies. In addition,
      VBM revealed significant hippocampal volume reduction bilaterally in all
      postmenopausal women compared with all premenopausal women. CONCLUSION: The
      results of the current study suggest that the menopause may be associated with
      hippocampal volume reduction.

PMID- 21182119
TI  - Relationship between sodium intensity and perfusion deficits in acute ischemic
      stroke.
AB  - PURPOSE: To assess the relationship between sodium signal intensity changes and
      oligemia, measured with perfusion-weighted imaging (PWI), in ischemic stroke
      patients. MATERIALS AND METHODS: Nine ischemic stroke patients (55 +/- 13 years),
      four with follow-up scans, underwent sodium and proton imaging 4-32 hours after
      symptom onset. Relative sodium intensity was calculated as the ratio of signal
      intensities in core (identified as hypertintense lesions on diffusion-weighted
      imaging [DWI]) or putative penumbra (PWI-DWI mismatch) to contralateral
      homologous regions. RESULTS: Sodium intensity increases in the core were not
      correlated with the severity of hypoperfusion, measured with either cerebral
      blood flow (rho = 0.157; P = 0.61) or cerebral blood volume (rho = -0.234; P =
      0.44). In contrast, relative sodium intensity was not elevated (4-7 hours 0.96 +/
      0.07; 17-32 hours 1.00 +/- 0.07) in PWI-DWI mismatch regions. CONCLUSION: Sodium
      signal intensity cannot be predicted by the degree of hypoperfusion acutely.
      Sodium intensity also remains unchanged in PWI-DWI mismatch tissue, indicating
      preservation of ionic homeostasis. Sodium magnetic resonance imaging (MRI), in
      conjunction with PWI and DWI, may permit identification of patients with viable
      tissue, despite an unknown symptom onset time.

PMID- 21182121
TI  - Reliability of two techniques for assessing cerebral iron deposits with
      structural magnetic resonance imaging.
AB  - PURPOSE: To test the reliability of two computational methods for segmenting
      cerebral iron deposits (IDs) in the aging brain, given that its measurement in
      magnetic resonance imaging (MRI) is challenging due to the similar effect
      produced by other minerals, especially calcium, on T2*-weighted sequences.
      MATERIALS AND METHODS: T1-, T2*-weighted, and fluid-attenuated inversion recovery
      (FLAIR) MR brain images obtained at 1.5T from 70 subjects in their early 70s who
      displayed a wide range of brain IDs were analyzed. The first segmentation method
      used a multispectral approach based on the fusion of two or more structural
      sequences registered and mapped in the red/green color space followed by Minimum
      Variance Quantization. The second method employed a combined thresholding, size
      and shape analysis using T2*-weighted images augmented with visual information
      from T1-weighted data. RESULTS: Both segmentation techniques had high intra- and
      interobserver agreement (95% confidence interval [CI] = +/- 57 voxels in a range
      from 0 to 1800), which decreased in subjects with significant microbleeds and/or
      IDs. However, the thresholding method was more observer dependent in identifying
      microbleeds and IDs boundaries than the multispectral approach. CONCLUSION: Both
      techniques proved to be in agreement and have good intra- and interobserver
      reliability. However, they have limitations, specifically with regard to
      automation and observer independence, so further work is required to develop
      fully user-independent methods of identifying cerebral IDs.

PMID- 21182122
TI  - Mapping developmental precentral and postcentral gyral changes in children on
      magnetic resonance images.
AB  - PURPOSE: To study the shape changes in precentral gyrus (PRG) and postcentral
      gyrus (PCG) during healthy brain development in childhood. MATERIALS AND METHODS:
      Magnetic resonance (MR) images from 20 healthy children scanned twice at 6.3 +/-
      0.8 and 8.1 +/- 0.9 years old were analyzed in this study. The analysis steps
      included: 1) The PRG and PCG were manually segmented from the MR images of each
      subject; 2) 3D mesh representing the PRG and PCG were built from the manually
      segmented images; 3) a series of shape description features were extracted and
      statistically analyzed by a permutation test method. RESULTS: This study showed
      the following statistically significant findings (P < 0.05): left PCG and PRG are
      located more posteriorly and superiorly than their right compartments; the
      hemispheric asymmetry of the PRG in the inferior-superior direction decreased
      after 2 years; the superior part of the PCG and PRG shifted and rotated to the
      posterior side of the brain. CONCLUSION: During normal pediatric brain
      development hemispheric asymmetry and shape of PCG and PRG are changed. These
      findings, together with previous reports in the literature, illustrate a region
      specific brain structure maturation pattern in children and may be related to
      changing neurocognitive functions.

PMID- 21182123
TI  - Low-dose 3D time-resolved magnetic resonance angiography (MRA) of the supraaortic
      arteries: correlation with high spatial resolution 3D contrast-enhanced MRA.
AB  - PURPOSE: To evaluate the feasibility of low-dose, 3D time-resolved contrast
      enhanced magnetic resonance angiography (TR-CEMRA) in the assessment of the
      supraaortic vessel, and to compare the results with high-resolution contrast
      enhanced MRA (HR-CEMRA). MATERIALS AND METHODS: This was an Institutional Review
      Board-approved retrospective study. Forty-five consecutive patients underwent
      contrast-enhanced 3D TR-CEMRA and 3D HR-CEMRA for evaluation of neurovascular
      disease at 3.0 T. Gadobutrol was administered at a constant dose of 1 mL for TR
      CEMRA (independent of patient weight), and 0.1 mmol/kg for HR-CEMRA. Two readers
      evaluated image quality using a four-point scale (from 0 = excellent to 3 =
      nondiagnostic), and subsequently graded each stenosis into clinically relevant
      categories: normal (0%), mild stenosis (<50%), moderate to severe (>50%), and
      occlusion. RESULTS: The overall image quality for low-dose TR-CEMRA was in the
      diagnostic range (median 0, range 0-3). On the grading of stenosis, TR-CEMRA
      using the TWIST sequence correlated with HR-CEMRA (r = 0.668, P < 0.001). In
      terms of the comparison of TR-CEMRA with HR-CEMRA, of the 675 supraaortic
      arterial segments evaluated for stenosis or occlusion, agreement occurred in 611
      of 675 (90.5%), overestimation in 41 of 675 (6.1%), and underestimation 23 of 675
      (3.4%). CONCLUSION: TR-CEMRA achieved by administration of a small contrast dose
      (1 cc) yields rapid and important functional and anatomical information in the
      evaluation of supraaortic arteries. Due to limited spatial resolution, TR-CEMRA
      at the current parameters has a tendency to overestimate the stenosis of smaller
      intracranial arteries compared to HR-CEMRA.

PMID- 21182124
TI  - High-resolution 3D coronary vessel wall imaging with near 100% respiratory
      efficiency using epicardial fat tracking: reproducibility and comparison with
      standard methods.
AB  - PURPOSE: To quantitatively assess the performance and reproducibility of 3D
      spiral coronary artery wall imaging with beat-to-beat respiratory-motion
      correction (B2B-RMC) compared to navigator gated 2D spiral and turbo-spin-echo
      (TSE) acquisitions. MATERIALS AND METHODS: High-resolution (0.7 * 0.7 mm) cross
      sectional right coronary wall acquisitions were performed in 10 subjects using
      four techniques (B2B-RMC 3D spiral with alternate (2RR) and single (1RR) R-wave
      gating, navigator-gated 2D spiral (2RR) and navigator-gated 2D TSE (2RR)) on two
      occasions. Wall thickness measurements were compared with repeated measures
      analysis of variance (ANOVA). Reproducibility was assessed with the intraclass
      correlation coefficient (ICC). RESULTS: In all, 91% (73/80) of acquisitions were
      successful (failures: four TSE, two 3D spiral (1RR) and one 3D spiral (2RR)).
      Respiratory efficiency of the B2B-RMC was less variable and substantially higher
      than for navigator gating (99.6 +/- 1.2% vs. 39.0 +/- 7.5%, P < 0.0001). Coronary
      wall thicknesses (+/- standard deviation [SD]) were not significantly different:
      1.10 +/- 0.14 mm (3D spiral (2RR)), 1.20 +/- 0.16 mm (3D spiral (1RR)), 1.14 +/-
      0.15 mm (2D spiral), and 1.21 +/- 0.17 mm (TSE). Wall thickness reproducibility
      ranged from good (ICC = 0.65, 3D spiral (1RR)) to excellent (ICC = 0.87, 3D
      spiral (2RR)). CONCLUSION: High-resolution 3D spiral imaging with B2B-RMC permits
      coronary vessel wall assessment over multiple thin contiguous slices in a
      clinically feasible duration. Excellent reproducibility of the technique
      potentially enables studies of disease progression/regression.

PMID- 21182125
TI  - Cardiac MRI to investigate myocardial scar and coronary venous anatomy using a
      slow infusion of dimeglumine gadobenate in patients undergoing assessment for
      cardiac resynchronization therapy.
AB  - PURPOSE: To evaluate a cardiac MR (CMR) examination with slow infusion of a high
      relaxivity contrast agent to visualize coronary venous anatomy (CVA) and
      myocardial scar in heart failure patients awaiting cardiac resynchronization
      therapy (CRT). MATERIALS AND METHODS: Fourteen patients awaiting CRT (seven
      ischemic cardiomyopathy (ICM) and seven non-ICM) and two with normal LV function
      underwent CMR on a 1.5 Tesla (T) MR scanner. Dimeglumine-gadobenate was slowly
      infused. Bolus arrival in the LV was measured by a dynamic electrocardiogram
      (ECG) -triggered inversion recovery (IR) scan subsequent to starting an ECG
      triggered respiratory-navigated three-dimensional (3D) SSFP MR scan with IR
      preparation to acquire systolic whole-heart anatomy for vein visualization.
      Delayed contrast-enhanced MR scan was performed to assess myocardial scar. CVA
      obtained by CMR was compared with X-ray venography in 11 patients. CVA and scar
      were segmented and registered for visual inspection. RESULTS: For all subjects,
      there was excellent visualization of the CVA. All ICM and one non-ICM patient
      showed scar. There was excellent correlation between veins seen by CMR and
      venography. CONCLUSION: We have demonstrated that slow infusion protocol of
      dimeglumine-gadobenate can be used to assess both CVA and myocardial scar in a
      single MR examination. Furthermore, an image overlay technique has been used to
      show the relationship of scar to the CVA.

PMID- 21182126
TI  - Dynamic contrast-enhanced magnetic resonance imaging and invasive breast cancer:
      primary lesion kinetics correlated with axillary lymph node extracapsular
      extension.
AB  - PURPOSE: To determine if dynamic contrast-enhanced (DCE) magnetic resonance
      imaging (MRI) peak enhancement (PE) of primary breast cancer can predict the
      presence of lymph node extracapsular extension (LNECE) in patients with axillary
      metastatic disease. MATERIALS AND METHODS: In all, 167 patients treated with
      radiotherapy for invasive breast cancer from January 1, 2006 to November 1, 2007
      were retrospectively identified. Patients with DCE-MRI and surgical axillary
      staging were included in this study. PE of primary tumors was compared according
      to axillary nodal status: negative, positive without LNECE, or positive with
      LNECE. A receiver operator characteristic curve (ROC) was plotted to determine
      accuracy of PE to predict LNECE. RESULTS: Forty-six patients met the study
      criteria. Thirty-two (70%) were node-negative, 9 (19%) were node-positive without
      LNECE, and 5 (11%) were node-positive with LNECE. PE was greater for patients
      with LNECE (mean 365%) compared to node-positive patients without LNECE (mean
      183%) P = 0.05 and node-negative patients (mean 144%) P = 0.0012. Area under the
      ROC curve was 0.93. CONCLUSION: DCE-MRI PE may be a surrogate marker for LNECE.
      If validated, DCE-MRI may provide noninvasive kinetic information informing
      axillary nodal status for patients who receive chemotherapy prior to surgical
      axillary staging or forego axillary dissection after a positive sentinel node
      biopsy.

PMID- 21182127
TI  - Correlation of the apparent diffusion coefficient value and dynamic magnetic
      resonance imaging findings with prognostic factors in invasive ductal carcinoma.
AB  - PURPOSE: To evaluate the correlation of the mean and minimal apparent diffusion
      coefficient values (ADC(mean) , ADC(minimal) ) and dynamic magnetic resonance
      imaging (MRI) findings with prognostic factors in invasive ductal carcinoma.
      MATERIALS AND METHODS: A total of 107 women with invasive ductal cancer underwent
      breast MRI. The ADC(mean) and ADC(minimal) of the cancers were computed. MRI
      findings were retrospectively evaluated according to the Breast Imaging Reporting
      and Data System (BI-RADS) lexicon: mass or nonmass type, mass shape, mass margin,
      nonmass distribution, and enhancement pattern. Histological records were reviewed
      for tumor size, lymph node metastasis, histologic grade, and expression of
      estrogen receptors (ER), progesterone receptors (PR), c-erbB-2(HER2), Ki-67, and
      epidermal growth factor receptors (EGFR). Correlations of ADC values and MR
      findings with prognostic factors were determined using the Mann-Whitney U-test
      and the Kruskal-Wallis test. RESULTS: The mean ADC(minimal) was 0.78 +/- 0.24 (*
      10-3 mm2 /s), and the mean ADC(mean) was 1.01 +/- 0.23 (* 10-3 mm2 /s). There was
      a significant correlation of the ADC(mean) value with ER expression (P = 0.027)
      and HER2 expression (P = 0.018). There was no significant relationship between
      ADC(minimal) and prognostic factors or between ADC(mean) and traditional
      prognostic factors, PR, Ki-67 and EGFR. The majority of the mass type lesions
      were less than 5 cm in size and the majority of nonmass type lesions were more
      than 2 cm in size (P = 0.022). The margin of mass was significantly associated
      with lymph node metastasis (P = 0.031), ER expression (P = 0.013), PR expression
      (P = 0.036), HER2 expression (P = 0.019), and EGRF expression (P = 0.041). The
      rim internal enhancement was significantly correlated with Ki-67 expression (P =
      0.008). CONCLUSION: The low ADC(mean) value was related to positive expression of
      ER and negative expression of HER2. A spiculated margin was related to a good
      prognosis, but rim enhancement was associated with a poor prognosis.

PMID- 21182128
TI  - Optimization of single injection liver arterial phase gadolinium enhanced MRI
      using bolus track real-time imaging.
AB  - PURPOSE: To measure contrast agent enhancement kinetics in the liver and to
      further evaluate and develop an optimized gadolinium enhanced MRI using a single
      injection real-time bolus-tracking method for reproducible imaging of the
      transient arterial-phase. MATERIALS AND METHODS: A total of 18 subjects with
      hypervascular liver lesions were imaged with four dimensional (4D) perfusion
      scans to measure time-to-peak (TTP) delays of arterial (aorta-celiac axis), liver
      parenchyma, liver lesion, portal, and hepatic veins. Time delays were calculated
      from the TTP-aorta signal, and then related to the gradient echo (GRE) k-space
      acquisition design, to determine optimized timing for real-time bolus-track
      triggering methodology. As another measure of significance, 200 clinical patients
      were imaged with 3D-GRE using either a fixed time-interval or by individualized
      arterial bolus real-time triggering. Bolus TTP-aorta was calculated and arterial
      phase acquisitions were compared for accuracy and reproducibility using specific
      vascular enhancement indicators. RESULTS: The mean bolus transit-time to peak
      lesion contrast was 8.1 +/- 2.7 seconds following arterial detection, compared to
      32.1 +/- 5.4 seconds from contrast injection, representing a 62.1% reduction in
      the time-variability among subjects (N = 18). The real-time bolus-triggered
      technique more consistently captured the targeted arterial phase (94%), compared
      to the fixed timing technique (73%), representing an expected improvement of
      timing accuracy in 28% of patients (P = 0.0001389). CONCLUSION: Our results show
      detailed timing window analysis required for optimized arterial real-time bolus
      triggering acquisition of transient arterial phase features of liver lesions,
      with optimized arterial triggering expected to improve reproducibility in a
      significant number of patients.

PMID- 21182129
TI  - Liver methylene fraction by dual- and triple-echo gradient-echo imaging at 3.0T:
      Correlation with proton MR spectroscopy and estimation of robustness after SPIO
      administration.
AB  - PURPOSE: To assess the systematic errors in liver methylene fraction (LMF)
      resulting from fat-fat interference effects with dual- and triple-echo gradient
      recalled-echo Dual/Triple GRE) sequences and to test the robustness of these
      sequences after iron overloading. MATERIALS AND METHODS: Forty type-2 diabetic
      patients underwent LMF measurement by 3.0T 1H magnetic resonance spectroscopy
      (corrected for T1 and T2 decays) as the reference standard and liver fat fraction
      (%Fat) measurement by four Dual/Triple GRE sequences with 20 degrees  and 60
      degrees  flip angle (alpha), corrected for T1 recovery. The same four sequences
      were repeated in eight patients after ferumoxide injection. Corrections for
      systematic errors were determined from the linear regressions (spectroscopy LMF
      values over Dual/Triple GRE %Fat values). Robustness was tested using Wilcoxon's
      signed-rank test. RESULTS: Fat-fat interference effects produced a ~10% relative
      systematic error and T2* decay produced a 1.9%-4.2% absolute systematic error in
      LMF. When comparing before and after ferumoxide, dual-echo imaging with alpha =
      20 degrees  and alpha = 60 degrees , even when corrected, showed absolute
      differences of 7.23% [2.81%-10.25%] (P = 0.0117) and 5.65% [1.89%-8.216.8%] (P =
      0.0117), respectively; compared to only 1.17% [0.08%-2.83%] (P = 0.0251) and
      1.15% [0.37%-2.73%] (P = 0.2626) with triple-echo imaging and alpha = 20 degrees 
      and alpha = 60 degrees , respectively. CONCLUSION: Triple-echo imaging with alpha
      = 60 degrees  corrected for both T1 recovery and fat-fat interference effects is
      robust after superparamagnetic iron oxide (SPIO) administration and can reliably
      quantify LMF.

PMID- 21182130
TI  - Diffusion-weighted imaging of the abdomen at 3.0 Tesla: image quality and
      apparent diffusion coefficient reproducibility compared with 1.5 Tesla.
AB  - PURPOSE: To compare single-shot echo-planar imaging (SS EPI) diffusion-weighted
      MRI (DWI) of abdominal organs between 1.5 Tesla (T) and 3.0T in healthy
      volunteers in terms of image quality, apparent diffusion coefficient (ADC)
      values, and ADC reproducibility. MATERIALS AND METHODS: Eight healthy volunteers
      were prospectively imaged in this HIPAA-compliant IRB-approved study. Each
      subject underwent two consecutive scans at both 1.5 and 3.0T, which included
      breathhold and free-breathing DWI using a wide range of b-values (0 to 800
      s/mm2). A blinded observer rated subjective image quality (maximum score= 8), and
      a separate observer placed regions of interest within the liver, renal cortices,
      pancreas, and spleen to measure ADC at each field strength. Paired Wilcoxon tests
      were used to compare abdominal DWI between 1.5T and 3.0T for specific
      combinations of organs, b-values, and acquisition techniques. RESULTS: Subjective
      image quality was significantly lower at 3.0T for all comparisons (P = 0.0078-
      0.0156). ADC values were similar at 1.5T and 3.0T for all assessed organs, except
      for lower liver ADC at 3.0T using b0-500-600 and breathhold technique. ADC
      reproducibility was moderate at both 1.5T and 3.0T, with no significant
      difference in coefficient of variation of ADC between field strengths.
      CONCLUSION: Compared with 1.5T, SS EPI at 3.0T provided generally similar ADC
      values, however, with worse image quality. Further optimization of abdominal DWI
      at 3.0T is needed.

PMID- 21182131
TI  - Diffusion-weighted magnetic resonance imaging of pancreatic adenocarcinomas:
      association with histopathology and tumor grade.
AB  - PURPOSE: To evaluate the utility of diffusion-weighted magnetic resonance imaging
      (DWI) in pancreatic ductal adenocarcinoma with various grades of differentiation.
      MATERIALS AND METHODS: Following Institutional Review Board (IRB) approval, 21
      consecutive patients with surgical pathology-proven pancreatic adenocarcinomas
      were retrospectively evaluated. Histopathologic characteristics and grades of
      differentiation of adenocarcinomas were analyzed. Twenty-one patients without a
      known history of pancreatic disease were evaluated as the control group. Anatomic
      MR images and DW images were acquired using 1.5-T MR systems. DWI with b values
      of 0 and 500 sec/mm2 were performed on both patients and control groups. The
      difference in mean apparent diffusion coefficient (ADC) values among groups of
      normal pancreatic parenchyma, adenocarcinomas with poor differentiation, and
      adenocarcinomas with well/moderate differentiation were compared using one-way
      analysis of variance. RESULTS: Mean ADCs of pancreatic adenocarcinomas (1.77 +/-
      0.45 * 10-3 mm2/sec) was not significantly lower than that of normal parenchyma
      (1.98 +/- 0.31) (P = 0.09). When adenocarcinomas were subdivided based on grades
      of differentiation, however, poorly differentiated adenocarcinoma with
      histopathologic characteristics of limited glandular formation and dense fibrosis
      had significantly lower ADCs (1.46 +/- 0.17) compared to those of well/moderately
      differentiated adenocarcinomas (2.10 +/- 0.42) characterized by neoplastic
      tubular structures (P < 0.01). Well/moderately differentiated adenocarcinomas
      with dense fibrosis showed significantly lower ADC values (1.49 +/- 0.19) than
      those with loose fibrosis (2.26 +/- 0.30) (P = 0.01). CONCLUSION: Difference in
      ADC values using DWI between poorly and well/moderately differentiated pancreatic
      ductal adenocarcinoma may relate to differences in glandular formation and
      density of fibrosis.

PMID- 21182132
TI  - Evaluation of respiratory liver and kidney movements for MRI navigator gating.
AB  - PURPOSE: To determine the tracking factor by studying the relationship between
      kidney and diaphragm motions and to compare the efficiency of the gating-and
      following and gating-only algorithms in reducing motion artifacts in navigator
      gated scans. MATERIALS AND METHODS: Diaphragm and kidney motions were measured by
      using real-time TrueFISP sequences from 10 healthy human volunteers to determine
      tracking factors at different acceptance windows. Mean tracking factors were used
      to calculate mean residual errors and improvement factors for the gating-and
      following and gating-only algorithms. RESULTS: Mean tracking factors for +/- 4,
      +/- 6, +/- 8 mm and full acceptance windows ranged from 0.6 to 0.7, with large
      interindividual variations. Acceptance rates increased as the size of the
      acceptance window increased (acceptance rate for a 4 mm window ~50%). There was a
      greater reduction of motion errors by gating-and-following (maximum of 1.86 mm)
      than gating-only (maximum of 7.05 mm). CONCLUSION: Mean tracking factors obtained
      in this study can be used as a guideline for using the gating-and-following
      algorithm in navigator-gated kidney scans. The gating-and-following and gating
      only algorithms were quantitatively compared, and it was found that the former is
      more effective in reducing motion errors.

PMID- 21182133
TI  - Gadoxetic acid disodium-enhanced magnetic resonance imaging for biliary and
      vascular evaluations in preoperative living liver donors: comparison with
      gadobenate dimeglumine-enhanced MRI.
AB  - PURPOSE: To compare gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic
      resonance imaging (MRI) with gadobenate dimeglumine (Gd-BOPTA)-enhanced MRI in
      preoperative living liver donors for the evaluation of vascular and biliary
      variations. MATERIALS AND METHODS: Sixty-two living liver donors who underwent
      preoperative MRI were included in this study. Thirty-one patients underwent MRI
      with Gd-EOB-DTPA enhancement, and the other 31 underwent MRI with Gd-BOPTA
      enhancement. Two abdominal radiologists retrospectively reviewed dynamic T1
      weighted and T1-weighted MR cholangiography images and ranked overall image
      qualities for the depiction of the hepatic artery, portal vein, hepatic vein, and
      bile duct on a 5-point scale and determined the presence and types of normal
      variations in each dynamic phase. Semiquantitative analysis for bile duct
      visualization was also conducted by calculating bile duct-to-liver contrast
      ratios. RESULTS: No statistical differences were found between the two contrast
      media in terms of hepatic artery or bile duct image quality by the two reviewers,
      or in terms of portal vein image quality by one reviewer (P > 0.05). Gd-BOPTA
      provided better image qualities than Gd-EOB-DTPA for the depiction of hepatic
      veins by both reviewers, and for the depiction of portal veins by one reviewer (P
      < 0.01). The two contrast media-enhanced images had similar bile duct-to-liver
      contrast ratios (P > 0.05). Regarding diagnostic accuracies with hepatic
      vascular/biliary branching types, no significant differences were observed
      between the two contrast media (P > 0.05). CONCLUSION: Gd-EOB-DTPA could be as
      useful as Gd-BOPTA for the preoperative evaluation of living liver donors, and
      has the advantage of early hepatobiliary phase image acquisition.

PMID- 21182134
TI  - Three-dimensional contrast-enhanced hepatic MR imaging: comparison between a
      centric technique and a linear approach with partial Fourier along both slice and
      phase directions.
AB  - PURPOSE: To compare the image quality of two variants of a three-dimensional (3D)
      gradient echo sequence (GRE) for hepatic MRI. MATERIALS AND METHODS: Thirty-nine
      patients underwent hepatic MRI on a 3.0 Tesla (T) magnet (Intera Achieva; Philips
      Medical Systems). The clinical protocol included two variants of a 3D GRE with
      fat suppression: (i) a "centric" approach, with elliptical centric k-space
      ordering and (ii) an "enhanced" approach using linear sampling and partial
      Fourier in both the slice and phase encoding direction. "Centric" and "Enhanced"
      3D GRE images were obtained both precontrast (n = 32) and after gadoxetic acid
      injection (n = 39). Two reviewers jointly reviewed MR images for anatomic
      sharpness, overall contrast, homogeneity, and absence of artifacts. The liver-to
      lesion signal difference ratio (SDR) was measured. Paired sample Wilcoxon test
      and paired t-tests were used. RESULTS: Enhanced 3D GRE images performed better
      than centric 3D GRE images with respect to anatomic sharpness (P = 0.0156),
      overall contrast (P = 0.0195), homogeneity (P < 0.0001), and absence of artifacts
      (P = 0.0003) on precontrast images. For postcontrast MRI, enhanced 3D GRE images
      showed better quality in terms of overall contrast (P = 0.0195), homogeneity (P <
      0.0001), and absence of artifacts (P = 0.009). Liver-to-lesion SDR on enhanced 3D
      GRE images (0.48 +/- 0.13) was significantly higher than that of conventional 3D
      GRE images (0.40 +/- 0.19, P = 0.0004) on postcontrast images, but not on
      precontrast images. CONCLUSION: The enhanced 3D GRE sequence available on our
      scanner provided better hepatic image quality than the centric variant, without
      compromising lesion contrast.

PMID- 21182135
TI  - Clinical utility of apparent diffusion coefficient (ADC) values in patients with
      prostate cancer: can ADC values contribute to assess the aggressiveness of
      prostate cancer?
AB  - PURPOSE: To retrospectively evaluate the relationship between apparent diffusion
      coefficient (ADC) values and Gleason score (GS) in prostate cancer. METHODS: A
      total of 60 patients who underwent radical prostatectomy for clinically localized
      prostate cancer were selected for this study. Diffusion-weighted magnetic
      resonance (MR) images were obtained using a 1.5 T system. ADC values were
      analyzed between three groups: GS of 6 or less (n = 7); GS of 7 (n = 37); and GS
      of 8 or higher (n = 16). ADC values of the three GS groups were statistically
      analyzed in order to determine the relationship with GS. In the 37 patients with
      GS = 7 the difference in ADC values between GS 3+4 and GS 4+3 was analyzed.
      RESULTS: Median ADC values (10-3 mm2 /s) of the three GS groups were 1.04 (GS = 6
      or less), 0.867 (GS = 7), and 0.729 (GS = 8 or higher). Although there was
      considerable overlap among the groups, the differences in ADC were statistically
      significant (P < 0.0001). There was a significant inverse correlation between GS
      and ADC values (z = -0.437, P < 0.0005). Median ADC values (10-3 mm2 /s) of GS
      3+4 and GS 4+3 patients were 0.88 and 0.814, respectively (P < 0.05). CONCLUSION:
      ADC values showed a negative correlation with GS. Pathologically, however, there
      was considerable intrasubject heterogeneity.

PMID- 21182136
TI  - Diagnostic value of delineating deep fascia in distinguishing between benign and
      malignant soft-tissue tumors in lower limbs using 3.0 T magnetic resonance
      imaging.
AB  - PURPOSE: To determine the association between morphological changes to the deep
      fascia and the malignancy of soft-tissue tumors in the lower limbs using 3.0 T
      magnetic resonance imaging (MRI). MATERIALS AND METHODS: MR images of 47
      consecutive patients with 48 pathologically proven soft-tissue tumors in the
      lower limbs were retrospectively reviewed by two radiologists. Lesions were
      divided into four groups according to their predominant location relative to the
      deep fascia: Group A: subcutaneous lesions superficial to the deep fascia (n =
      9); Group B: lesions located beneath the deep fascia (n = 8); Group C: lesions
      centered in the interspaces of the deep fascia investment (n = 11); and Group D:
      intramuscular lesions (n = 20). RESULTS: The deep fascial structures were
      complete in all of the 19 benign lesions. In malignant lesions, destruction signs
      of the deep fascia were observed in 27 of the 29, which were characterized by
      disappearance/disruption of the fascial line and aggressive growth penetrating
      through the fascial line into the adjacent compartment, or
      disappearance/disruption of the intermuscular septa and embedding the mutilated
      fascial septa within the lesion, or destruction of the fascia-muscle planes and
      abolishment of the deep fascial interspaces. Diagnosis of malignancy based on the
      signs of destruction of the deep fascial structure delineated with 3.0 T MRI, the
      sensitivity, specificity, and accuracy were 93.10%, 100%, and 95.83%,
      respectively. CONCLUSION: Tumor involvement and destruction of the deep fascial
      structures visualized by 3.0 T MRI may be of utility in differentiating malignant
      from benign soft-tissue tumors.

PMID- 21182137
TI  - Advanced morphological 3D magnetic resonance observation of cartilage repair
      tissue (MOCART) scoring using a new isotropic 3D proton-density, turbo spin echo
      sequence with variable flip angle distribution (PD-SPACE) compared to an
      isotropic 3D steady-state free precession sequence (True-FISP) and standard 2D
      sequences.
AB  - PURPOSE: To evaluate a new isotropic 3D proton-density, turbo-spin-echo sequence
      with variable flip-angle distribution (PD-SPACE) sequence compared to an
      isotropic 3D true-fast-imaging with steady-state-precession (True-FISP) sequence
      and 2D standard MR sequences with regard to the new 3D magnetic resonance
      observation of cartilage repair tissue (MOCART) score. MATERIALS AND METHODS:
      Sixty consecutive MR scans on 37 patients (age: 32.8 +/- 7.9 years) after matrix
      associated autologous chondrocyte transplantation (MACT) of the knee were
      prospectively included. The 3D MOCART score was assessed using the standard 2D
      sequences and the multiplanar-reconstruction (MPR) of both isotropic sequences.
      Statistical, Bonferroni-corrected correlation as well as subjective quality
      analysis were performed. RESULTS: The correlation of the different sequences was
      significant for the variables defect fill, cartilage interface, bone interface,
      surface, subchondral lamina, chondral osteophytes, and effusion (Pearson
      coefficients 0.514-0.865). Especially between the standard sequences and the 3D
      True-FISP sequence, the variables structure, signal intensity, subchondral bone,
      and bone marrow edema revealed lower, not significant, correlation values (0.242
      0.383). Subjective quality was good for all sequences (P >= 0.05). Artifacts were
      most often visible on the 3D True-FISP sequence (P < 0.05). CONCLUSION: Different
      isotropic sequences can be used for the 3D evaluation of cartilage repair with
      the benefits of isotropic 3D MRI, MPR, and a significantly reduced scan time,
      where the 3D PD-SPACE sequence reveals the best results.

PMID- 21182138
TI  - Usefulness of diffusion-weighted imaging for differentiating between desmoid
      tumors and malignant soft tissue tumors.
AB  - PURPOSE: To evaluate the usefulness of diffusion-weighted imaging (DWI) for
      differentiating between desmoid tumors and malignant soft tissue tumors.
      MATERIALS AND METHODS: Conventional MRI and DWI were performed for 8 desmoid
      tumors and 74 malignant soft tissue tumors. DWI was obtained with a single-shot
      echo-planar imaging sequence using a 1.5 Tesla (T) MR imager. DW images were
      acquired with motion-probing gradient pulses applied along three directions (x,
      y, and z axes) with three b-factors (0, 500, and 1000 s/mm2). Two observers
      blinded to clinical information measured three regions of interest within the
      solid tumor and selected a minimum apparent diffusion coefficient () in each
      lesion. The mean ADC of desmoid tumors was calculated and compared with that of
      malignant soft tissue tumors using the Mann-Whitney U test. RESULTS: The mean ADC
      of desmoid tumors and malignant soft tissue tumors was 1.36 +/- 0.48 * 10-3 mm2
      /s and 0.88 +/- 0.20 * 10-3 mm2 /s (mean +/- SD), respectively. The mean ADC of
      the desmoid tumors was significantly higher than that of malignant soft tissue
      tumors (P < 0.01). CONCLUSION: DWI is considered to be useful for differentiating
      between desmoid tumors and malignant soft tissue tumors. In the future, further
      investigation in a large series is necessary.

PMID- 21182139
TI  - T1-weighted ultrashort echo time method for positive contrast imaging of magnetic
      nanoparticles and cancer cells bound with the targeted nanoparticles.
AB  - PURPOSE: To obtain positive contrast based on T1 weighting from magnetic iron
      oxide nanoparticle (IONP) using ultrashort echo time (UTE) imaging and
      investigate quantitative relationship between positive contrast and the core size
      and concentration of IONPs. MATERIALS AND METHODS: Solutions of IONPs with
      different core sizes and concentrations were prepared. T1 and T2 relaxation times
      of IONPs were measured using the inversion recovery turbo spin echo (TSE) and
      multi-echo spin echo sequences at 3 Tesla. T1 -weighted UTE gradient echo and T2
      weighted TSE sequences were used to image IONP samples. U87MG glioblastoma cells
      bound with arginine-glycine-aspartic acid (RGD) peptide and IONP conjugates were
      scanned using UTE, T1 and T2-weighted sequences. RESULTS: Positive contrast was
      obtained by UTE imaging from IONPs with different core sizes and concentrations.
      The relative-contrast-to-water ratio of UTE images was three to four times higher
      than those of T2-weighted TSE images. The signal intensity increases as the
      function of the core size and concentration. Positive contrast was also evident
      in cell samples bound with RGD-IONPs. CONCLUSION: UTE imaging allows for imaging
      of IONPs and IONP bound tumor cells with positive contrast and provides contrast
      enhancement and potential quantification of IONPs in molecular imaging
      applications.

PMID- 21182140
TI  - Quantification of fat infiltration in oculopharyngeal muscular dystrophy:
      comparison of three MR imaging methods.
AB  - PURPOSE: To analyze and compare three quantitative MRI methods to determine the
      degree of muscle involvement in oculopharyngeal muscular dystrophy (OPMD).
      MATERIALS AND METHODS: Muscle fat content (MFC) was determined based on water-fat
      quantification using a 2-point Dixon (2PD) method and on a histogram analysis of
      the free induction decay (FID) signal of a gradient-spoiled steady-state free
      precession (SSFP) sequence. In addition, transverse relaxation times (T2) of
      muscle tissue were calculated using a monoexponential decay model. RESULTS: We
      observed an increased mean MFC in OPMD patients as compared to healthy controls
      with the adductor magnus and soleus muscles being the most involved muscles in
      the thigh and calf, respectively. Furthermore, strong correlations (0.78 < R2 <
      0.94) between different quantitative MR methods were observed. Fewer outliers,
      however, were obtained by the 2PD method and T2 measurements, suggesting these
      methods being superior to the SSFP-FID method. CONCLUSION: Quantitative MR
      techniques, such as fast multiecho Dixon methods and T2 imaging, can reliably
      differentiate between healthy and dystrophic muscles in OPMD, even if muscles are
      only marginally affected. Quantitative methods thus represent a promising tool
      that may be able to monitor more objectively the individual disease progression
      and treatment response in future clinical trials in muscular dystrophies.

PMID- 21182141
TI  - Papillary muscle involvement in myocardial infarction: initial results using
      multicontrast late-enhancement MRI.
AB  - We hypothesized that multicontrast late-enhancement (MCLE) MRI would improve the
      identification of papillary muscle involvement (PM-MI) in patients with
      myocardial infarction (MI), compared with conventional late gadolinium
      enhancement (LGE) MRI using the inversion recovery fast gradient echo (IR-FGRE)
      technique. Cardiac LGE-MRI studies using both MCLE and IR-FGRE pulse sequences
      were performed on a 1.5 Tesla (T) MRI system in 23 patients following MI. In all
      patients, PM-MI was confirmed by the diagnostic criteria as outlined below: (a)
      the increased signal intensity of PM was the same or similar to that of adjacent
      hyper-enhanced left ventricular (LV) infarct segments; and (b) the hyper-enhanced
      PM region was limited to the PM area defined by precontrast cine images of steady
      state free precession (SSFP). Visual contrast score was rated according to the
      differentiation between LV blood pool and hyper-enhanced infarct myocardium.
      Quantitative contrast-noise ratios (CNR) of infarct relative to blood pool and
      viable myocardium were also measured on MCLE and IR-FGRE images. Of these 23
      patients, 13 studies demonstrated primarily involvement of the territories of the
      right coronary (RCA, 8 patients) and/or left circumflex (LCX, 5 patients)
      arteries and 10 involved the territories of left anterior descending artery (LAD)
      with some LCX involvement. Although both IR-FGRE and MCLE determined the presence
      and extent of LV MI, better visual contrast scores were achieved in MCLE (2.9 +/-
      0.3) compared with IR-FGRE (1.6 +/- 0.8, P < 0.001). The CNRs of infarct relative
      to LV blood pool showed a significant statistical difference (n = 23, P <
      0.00001) between MCLE (16.2 +/- 7.2) and IR-FGRE images (4.8 +/- 4.1), which is
      consistent with the result of visual contrast scores between infarct and LV blood
      pool. The CNRs of infarct versus viable myocardium did not demonstrate a
      significant statistical difference (n = 23, P = 0.61) between MCLE (14.4 +/- 7.0)
      and IR-FGRE images (13.6 +/- 6.1). MCLE clearly demonstrated PM-MI in all cases
      (100%, 23/23) while only 39% (9/23) could be visualized on the corresponding IR
      FGRE images. In conclusion, MCLE imaging provides better contrast between blood
      pool and infarct myocardium, thus improving the determination of PM-MI.

PMID- 21182142
TI  - Renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion:
      radiological findings mimicking papillary subtype.
AB  - The authors describe the computed tomography (CT) and magnetic resonance imaging
      (MRI) findings of an 18-year-old man with renal cell carcinoma (RCC) associated
      with the Xp11.2 translocation/transcription factor E3 (TFE3) gene fusion (Xp11
      translocation carcinoma). The lesion was hyperdense on unenhanced CT,
      hypovascular on contrast-enhanced studies, hypointense on T2-weighted MR images,
      and hemosiderin deposition was suspected on phase-shift gradient-echo MR images.
      Histopathological specimens revealed pathological findings resembling papillary
      RCC predominantly and exhibited immunoreactivity for TFE3. Because there is often
      considerable morphological overlap between this carcinoma and papillary RCC, the
      imaging findings of Xp11 translocation carcinoma may be similar to those of the
      papillary subtype. Therefore, Xp11 translocation carcinoma should be considered,
      particularly in young patients when radiologic images demonstrate a renal tumor
      mimicking the papillary subtype.

PMID- 21182143
TI  - Lipoma arborescens of the peroneal tendon sheath.
AB  - Lipoma arborescens or synovial lipomatosis is a rare disorder characterized by
      mature fat infiltration of hypertrophic synovial villi, most frequently affecting
      the suprapatellar pouch of the knee. Involvement of the synovial tendon sheath is
      extremely rare with only a few reported cases in the literature. We present a
      case of lipoma arborescens involving the peroneal and flexor tendons sheaths of
      the ankle, review the few reported cases to date, and discuss MR imaging features
      of this rare entity.

PMID- 21182144
TI  - Time-resolved magnetic resonance angiography: evaluation of intrapulmonary
      circulation parameters in pulmonary arterial hypertension.
AB  - PURPOSE: To determine whether pulmonary arterial and venous transit times
      measured by time-resolved magnetic resonance angiography (MRA) can be used as a
      diagnostic tool for pulmonary arterial hypertension (PAH). MATERIALS AND METHODS:
      Twelve patients with confirmed PAH and 10 healthy volunteers were scanned with
      Institutional Review Board (IRB) approval. Time-resolved MRA and 2D phase
      contrast flow images of the pulmonary vasculature were acquired. Pulmonary
      arterial and venous transit times (PaTT and PvTT) and pulmonary valve flow (PVF)
      were obtained. Pulmonary arterial and pulmonary venous blood volumes (PaBV and
      PvBV) were calculated as the product of flow and transit time. RESULTS: Patients
      with PAH showed statistically significant increases in PaTT and PvTT (P < 0.0004,
      P < 0.05, respectively) compared to controls. PaBV (165.2 +/- 92.0 mL) was
      significantly higher in PAH subjects than controls (97.0 +/- 47.1 mL) (P < 0.04),
      whereas PvBV (127.9 +/- 148.9 mL) of PAH subjects had no significant increase
      from those of healthy controls (142.5 +/- 104.1 mL) (P < 0.38). CONCLUSION:
      Pulmonary arterial transit times measured using time-resolved MRA can be used as
      a simple, noninvasive metric for detection of altered hemodynamics in PAH.

PMID- 21182145
TI  - Automatic segmentation propagation of the aorta in real-time phase contrast MRI
      using nonrigid registration.
AB  - PURPOSE: To assess the use of a nonrigid registration technique for semi
      automatic segmentation of the aorta from real-time velocity mapping MRI.
      MATERIALS AND METHODS: Real-time phase contrast images were acquired to measure
      flow and stroke volumes in 10 subjects, during free breathing, at rest, and
      during exercise. A nonrigid registration algorithm was developed to propagate a
      manually drawn region of interest in the aorta from one frame to all other frames
      of the real-time sequence (148 images). Thus the technique provided a semi
      automatic segmentation over the whole sequence of images. The accuracy was
      assessed by comparison with manual segmentations in terms of Dice overlap
      measures and stroke volumes (SV). RESULTS: Semi-automatic segmentations were
      comparable to manual ones (Dice score of 0.89 +/- 0.04). Inter-observer
      reproducibility was similar for manual and semi-automatic segmentations (Dice
      score of 0.90 +/- 0.04 in both cases, the difference was not significant). SV
      measurements also showed good agreement between manual and semi-automatic
      segmentations (correlation coefficient r > 0.94), and the differences were not
      statistically significant. CONCLUSION: Although real-time phase contrast images
      have compromised image quality, a fast and robust segmentation of the aorta was
      possible using the registration-based technique.

PMID- 21182146
TI  - Effects of postprandial state and mesenteric blood flow on the repeatability of
      MR elastography in asymptomatic subjects.
AB  - PURPOSE: To determine the repeatability of stiffness measurements in the liver
      using MR elastography (MRE) during the fasted and fed states. MRE has gained
      increased recognition as a noninvasive method to quantify fibrotic changes in the
      liver. It is well known that eating increases splanchnic blood flow, and fasting
      status of patients has been recognized as a factor that may affect hepatic
      stiffness measured with MRE. MATERIALS AND METHODS: Hepatic MRE stiffness and
      flow through the superior mesenteric vein (SMV) were measured in 12 healthy
      subjects in fasted and fed states, and measurements were repeated 5 weeks later.
      A linear mixed effects model was used to estimate the sources of variability in
      the data, which included day (exams on different days) and subject. Sources were
      combined to calculate the overall standard deviation of a single MRE measurement.
      RESULTS: The total within-subject standard deviation of an MRE exam is 8.5%
      (standard error [SE] = 1.7%) or 9.0% (SE = 1.8%) for fasted and fed states,
      respectively. No significant differences between fasted/fed state stiffness and
      no correlation between hepatic stiffness and SMV flow were observed. CONCLUSION:
      As seen in this smaller population, healthy subjects scanned in a known fasted or
      fed state provide repeatable stiffness estimates with no relationship to SMV
      flow.

PMID- 21182147
TI  - High-resolution interleaved water-fat MR imaging of finger joints with chemical
      shift elimination.
AB  - PURPOSE: To study the use of an interleaved water-fat (IWF) sequence with a
      custom-made radiofrequency (RF) coil for high-resolution imaging of arthritic
      finger joints. MATERIALS AND METHODS: High-resolution finger magnetic resonance
      imaging (MRI) was performed using a custom-made dedicated RF receiver coil and an
      IWF sequence. A phantom, a cadaver finger specimen, and the fingers of two normal
      controls and six arthritic subjects were imaged with a resolution of 156 * 156 *
      600 MUm. The appearance of anatomic structures on the IWF images were compared
      with images acquired with a regular sequence. The images were reviewed by two
      musculoskeletal radiologists for the depiction of anatomical structures and for
      the presence of abnormalities. RESULTS: The high-resolution images revealed
      detailed structures of the finger joints not detectable using typical clinical
      resolution. The IWF sequence gave more realistic depiction of subchondral bone
      thickness, and avoided false bone erosions displayed in the regular sequence. It
      also allowed better visualization of ligaments and tendons. CONCLUSION: This
      pilot study shows the feasibility and the potential usefulness of high-resolution
      IWF imaging for finger joint evaluation. This technique may be useful for the
      diagnosis and treatment assessment of arthritis, and for the study of joint
      disease pathogenesis.

PMID- 21182148
TI  - Controversial findings in "three-dimensional velocity mapping of thoracic aorta
      and supra-aortic arteries in Takayasu arteritis".

PMID- 21182150
TI  - Combining electronic healthcare databases in Europe to allow for large-scale drug
      safety monitoring: the EU-ADR Project.
AB  - PURPOSE: In this proof-of-concept paper we describe the framework, process, and
      preliminary results of combining data from European electronic healthcare record
      (EHR) databases for large-scale monitoring of drug safety. METHODS: Aggregated
      demographic, clinical, and prescription data from eight databases in four
      countries (Denmark, Italy, Netherlands, the UK) were pooled using a distributed
      network approach by generation of common input data followed by local aggregation
      through custom-built software, Jerboa((c)). Comparison of incidence rates of
      upper gastrointestinal bleeding (UGIB) and nonsteroidal anti-inflammatory drug
      (NSAID) utilization patterns were used to evaluate data harmonization and quality
      across databases. The known association of NSAIDs and UGIB was employed to
      demonstrate sensitivity of the system by comparing incidence rate ratios (IRRs)
      of UGIB during NSAID use to UGIB during all other person-time. RESULTS: The study
      population for this analysis comprised 19,647,445 individuals corresponding to
      59,929,690 person-years of follow-up. 39,967 incident cases of UGIB were
      identified during the study period. Crude incidence rates varied between 38.8 and
      109.5/100,000 person-years, depending on country and type of database, while age
      standardized rates ranged from 25.1 to 65.4/100,000 person-years. NSAID use
      patterns were similar for databases within the same country but heterogeneous
      among different countries. A statistically significant age- and gender-adjusted
      association between use of any NSAID and increased risk for UGIB was confirmed in
      all databases, IRR from 2.0 (95%CI:1.7-2.2) to 4.3 (95%CI: 4.1-4.5). CONCLUSIONS:
      Combining data from EHR databases of different countries to identify drug-adverse
      event associations is feasible and can set the stage for changing and enlarging
      the scale for drug safety monitoring.

PMID- 21182151
TI  - The potentially inappropriate prescription of new drug: thiazolidinediones for
      patients with type II diabetes in Taiwan.
AB  - PURPOSE: To examine the potentially inappropriate prescription of
      thiazolidinediones (TZD). METHODS: Data on TZD prescriptions were collected from
      Taiwan's National Health Insurance dataset from 2001 to 2006. TZDs were
      considered inappropriately prescribed when they were prescribed to patients who
      were (1) under 18 years old, (2) pregnant, who had (3) type 1 diabetes, (4)
      severe heart failure, (5) hepatic insufficiency, or (6) renal insufficiency and
      taking TZD + metformin in combination. We aggregated potentially inappropriate
      prescriptions of TZD for each health-care institution in each month starting from
      March 2001, when TZD was introduced to Taiwan's market. RESULTS: The potentially
      inappropriate prescription of TZD increased from 9.41% in 2001 to 12.50% in 2006.
      Prior inappropriate prescription led to a 0.06% (95%CI: 0.04-0.08) further
      increase in its later inappropriate prescription. Accumulated months of
      experience prescribing TZD was found associated with higher proportion of
      inappropriate prescription of TZD (0.03%, 95%CI: 0.01-0.05). However, it was
      negatively associated with new incidence of inappropriate prescription of TZD (
      0.20, 95%CI: -0.22 to -0.18). The greater the volume of prior TZD prescription (
      0.87%, 95%CI: -0.93 to -0.81) and the greater the number of accumulated months
      since adoption (-0.14%, 95%CI: -0.16 to -0.12), the greater the decrease in rates
      of new inappropriate prescriptions. CONCLUSIONS: Along with the quick penetration
      of the new DM drug came an increased possibility that it would be prescribed
      inappropriately, a trend that persisted over time.

PMID- 21182152
TI  - The effect of incident antidiabetic regimens on lipid profiles in veterans with
      type 2 diabetes: a retrospective cohort.
AB  - OBJECTIVE: Effects of oral antidiabetic drugs (OADs) on lipids may influence
      cardiovascular outcomes. Our aim was to compare time to initiation of lipid
      lowering medication (LLM) and 12-month lipid profiles among new OAD users.
      METHODS: We identified a retrospective cohort of 17,774 veterans who received
      care at Veterans Administration (VA) Mid-South Network with a first OAD from 1
      January 2000 to 31 December 2007. There were 6917 patients (38.9%) not on a LLM
      at baseline, and 3871 (56%) had complete covariates. Incident users of
      sulfonylurea and combination metformin + sulfonylurea were compared to metformin
      users for time to LLM initiation. Incident users of these OADs and
      thiazolidendiones were included in comparison of 12-month low-density lipoprotein
      (LDL), high-density lipoprotein (HDL), triglycerides (TGs), and total
      cholesterol. All analyses adjusted for demographics, lipids, HbA1C, healthcare
      utilization, and cardiovascular disease at baseline. RESULTS: The median time to
      starting LLM was 2.35 years (interquartile range 0.96, 4.6) following metformin
      initiation and not statistically different for users of sulfonylureas, or
      combination OADs. Compared to metformin users, 12-month HDL was 1.35 mg/dl
      (95%CI: -2.01, -0.72) lower and TGs were 5.7% higher (95%CI: 1.5%, 10.0%) for
      sulfonylurea users; TGs were 24.8% (95%CI: 0.7%, 54.5%) higher for
      thiazolidinedione users. Statin users had LDL and total cholesterol 16.7 mg/dl
      (95%CI: -19.9, -13.5) and 18.6 mg/dl (95%CI: -22.1, -15.1) lower than non-statin
      users, respectively. CONCLUSIONS: Time to LLM initiation was similar between
      OADs. Metformin use resulted in more favorable lipids at 12 months compared to
      sulfonylureas or thiazolidinediones.

PMID- 21182153
TI  - Guideline-conformity of initiation with oral hypoglycemic treatment for patients
      with newly therapy-dependent type 2 diabetes mellitus in Austria.
AB  - PURPOSE: To determine guideline conformity of initiation of oral hypoglycemic
      (OH) treatment for type 2 diabetes in Austria; to study patient and prescriber
      correlates of recommended initiation with metformin monotherapy. METHODS: We used
      claims from 11 sickness funds that covered 7.5 million individuals, representing
      >90% of the Austrian population. First-time OH use was defined as a first filled
      prescription after one year without any OH drug or insulin. Among these incident
      users, we described the OH drug class used and defined correlates of initiation
      with metformin monotherapy. RESULTS: From 1/2007 to 6/2008, we identified 42,882
      incident users of an OH drug: 70.8% used metformin, 24.7% used a sulfonylurea,
      and 4.5% initiated treatment with another class. We estimated the incidence of OH
      dependent type 2 diabetes at 3.8-4.4 per 1000 patient-years. We conducted
      multivariate analyses among 39 077 patients with available prescriber
      information. Independent correlates of initiation with metformin were younger
      age, female gender, waived co-payment, more recent initiation, fewer hospital
      days and more therapeutic classes received in the year prior to first OH therapy
      (all p < 0.001). Prescriber specialty and age (p < 0.001), but not gender, were
      also associated with metformin initiation. Approximately 20% of metformin
      initiators had a second OH drug added within <18 months. While we were unable to
      ascertain specific contraindications to metformin (renal insufficiency, hepatic
      failure), <10% of the general population are expected to have these conditions.
      CONCLUSIONS: Seventy per cent of new initiators of OH treatment in Austria
      received metformin as recommended by international guidelines. At least 20% did
      not, taking into account possible contraindications, which provides an
      opportunity for intervention.

PMID- 21182154
TI  - Small area variation and geographic and patient-specific determinants of
      metabolic testing in antipsychotic users.
AB  - PURPOSE: The American Diabetes Association and American Psychiatric Association
      recommend metabolic monitoring for all patients using second-generation
      antipsychotic (SGA) drugs. We estimated glucose and lipid testing rates among SGA
      users from three state Medicaid programs and investigated small area variation
      and patient and geographic determinants of testing. METHODS: A retrospective new
      user cohort study using Medicaid claims data from California, Missouri, and
      Oregon was conducted among 30,563 patients in 207 counties starting SGA
      medication September 2004-December 2005. Adjusted odds ratios for state, county,
      and patient factors associated with testing were calculated from multivariable
      hierarchical logistic regression models. RESULTS: Mean 6-month testing rates were
      51.6% (glucose) and 26.2% (lipids). Screening rates were positively associated
      with the number of Type 2 diabetes risk factors (RF) present: glucose -39% (0 RF)
      to 82% (5 RF); lipids -13% (0 RF) to 66% (5 RF). A four-fold difference in
      glucose testing rates (21-85%) and a greater than six-fold difference in lipid
      testing rates (0-62%) were observed between counties. In the adjusted regression
      models, age, cardiometabolic co-morbidity (diabetes, dyslipidemia), serious
      mental illness, persistent use of SGAs, and frequency of non-psychiatric medical
      office visits were significant determinants of glucose and lipid testing. Lipid
      testing was more likely for children and adults in California, as was glucose
      testing for children. CONCLUSIONS: Glucose and lipid testing among SGA-users
      varied significantly between states, counties, and by patient characteristics.
      More effort is needed to understand provider and system reasons for testing
      disparities in order to inform risk management quality improvement interventions.

PMID- 21182155
TI  - Estimating pediatric inpatient medication use in the United States.
AB  - PURPOSE: We demonstrated the feasibility of developing national estimates of
      pediatric inpatient medication use by analyzing data from a large administrative
      database. METHODS: Pediatric inpatient data were extracted from Premier
      Perspective(r) database to calculate the prevalence of use of specific
      medications among hospitalized children in 2008. The database was validated by
      comparing characteristics to the HCUP KID sample of pediatric hospitalizations
      for 2006. Prevalence was calculated by categorizing patients as ever or never
      having received a specific drug. RESULTS: The 10 drugs administered in the most
      pediatric hospitalizations were acetaminophen, lidocaine, ampicillin, gentamicin,
      fentanyl, ibuprofen, morphine, ondansetron, ceftriaxone, and albuterol.
      CONCLUSIONS: Although the database is not a probability-based sample, it bears
      sufficient similarity to a probability-based sample of pediatric hospitalizations
      (HCUP KID) to serve as a starting point in developing national estimates of
      inpatient pediatric medication use. Over 500 drug entities were administered to
      hospitalized children, but most are used by small percentages of hospitalized
      patients. The small numbers of children using any one drug has implications for
      efforts to study efficacy and safety, describe off-label use, monitor adverse
      events, describe practice, and conduct comparative effectiveness research.

PMID- 21182157
TI  - The association between smoking and subsequent repeated use of prescribed opioids
      among adolescents and young adults--a population-based cohort study.
AB  - BACKGROUND: The use of prescribed opioids for chronic non-cancer pain is
      increasing in many countries. It is, therefore, important to investigate
      predictors for repeated use of opioids in young non-cancer patients. OBJECTIVE:
      The aim of this study was to prospectively evaluate adolescent smoking and its
      association with repeated use of prescription opioids in adolescents/young adults
      without cancer. METHODS: The study population consisted of 11,809 15-16 year old
      participants (86% participation rate) in the Norwegian Youth Health Surveys
      carried out in 2000-2003. The exposure variable, self reported smoking status,
      was registered in the youth surveys along with potential confounders. Repeated
      use of opioids, defined as 4+ prescriptions recorded in the nationwide Norwegian
      Prescription Database during 2004-2008, was used as outcome measure. RESULTS:
      Among the participants included in our study, 161 had redeemed 4+ prescriptions
      for opioids. Daily adolescent smoking was associated with repeated use of opioids
      with an adjusted OR of 2.2 (95% CI 1.3-3.5). CONCLUSIONS: Daily smoking at 15-16
      years of age was associated with increased risk of incident repeated use of
      prescribed opioids later in life. Our study suggests that smoking dependence in
      adolescents may predict longer lasting and/or higher levels of opioid use.

PMID- 21182158
TI  - Did the removal of the indication of nocturnal enuresis for intranasal
      desmopressin change prescribing practice?
AB  - PURPOSE: The indication for the treatment of primary nocturnal enuresis was
      removed from all intranasal preparations of desmopressin in May 2007. Objective
      of this study was to examine whether and how fast this regulatory decision
      changed prescribing in affected children. METHODS: We analyzed claims data of the
      Gmunder ErsatzKasse (GEK) over the years 2004-2008. All children and adolescents
      aged 0-18 years who received at least one out-patient diagnosis of urinary
      incontinence in the corresponding years were included. Our outcome of interest
      was the proportion of oral desmopressin and its change over time. RESULTS: A
      total of 6308 to 7207 children with a mean age of about 8 years were included
      annually (62-63% were male) and 14 746 packages of desmopressin were analysed
      (49.9% intranasal; 50.1% oral; 0.01% parenteral preparations). The proportion of
      patients using desmopressin decreased slightly from 13.9% in 2004 to 12.6% in
      2008 ( p for trend = 0.0131). Between January 2004 (39.1%) and December 2006
      (41.3%), the proportion of oral forms was nearly constant and doubled after that
      within a few months to about 80%. CONCLUSIONS: Immediately after the removal of
      the indication for intranasal desmopressin, an increased prescribing of tablet
      forms in affected children was found in Germany.

PMID- 21182156
TI  - Demographic, medical, and behavioral characteristics associated with over the
      counter non-steroidal anti-inflammatory drug use in a population-based cohort:
      results from the Multi-Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: Three types of non-steroidal anti-inflammatory drugs (NSAIDs) can be
      obtained both over the counter (OTC) and by prescription in the United States.
      OTC NSAID use is not recorded in prescription claims databases; this might lead
      to differential misclassification of NSAID exposure status in studies that use
      computerized pharmacy databases to study NSAID use. OBJECTIVE: To evaluate
      characteristics of OTC versus prescription NSAID users. METHODS: This analysis is
      set within the Multi-Ethnic Study of Atherosclerosis (MESA) study; a prospective
      cohort study of 6814 adults from four ethnic groups (European descent, Asian,
      African-American, and Hispanic) with a mean age of 62 years. The cohort was
      restricted to those who initiated NSAID use (aspirin, ibuprofen, or naproxen)
      during follow-up. We compared information about age, sex, ethnicity, body mass
      index, smoking, diabetes, medication use, education, income, health insurance
      status, and exercise between groups. RESULTS: OTC NSAID use was prevalent at
      baseline (25% aspirin, 9% ibuprofen, and 2% naproxen). Compared to prescribed
      NSAID use, OTC NSAID use was lower for users of non-European descent for all
      classes: aspirin (p < 0.0001), ibuprofen (p < 0.0001), and naproxen (p = 0.0094).
      For aspirin, differences were seen for male gender (relative risk (RR): 0.92;
      95%confidence interval (CI): 0.86-0.98), use of lipid lowering drugs (RR: 0.88;
      95%CI: 0.80-0.96), low income (RR: 0.89; 95%CI: 0.81-0.97), and participants one
      standard deviation above average in intentional exercise (RR: 1.03; 95%CI: 1.01
      1.05). CONCLUSIONS: OTC NSAID use is prevalent in an older multi-ethnic
      population and OTC users differ from prescription NSAID users. Caution should be
      exercised when using prescribed NSAIDs as a proxy for NSAID use.

PMID- 21182159
TI  - Do antidepressants reduce the effectiveness of tamoxifen?

PMID- 21182165
TI  - Monitoring treatment response of childhood acute lymphocytic leukemia with
      certain molecular and biochemical markers.
AB  - Apoptosis is the primary mechanism through which most chemotherapeutic agents
      induce tumor cell death. The purpose of this study was to monitor the expression
      of pro- and anti-apoptotic proteins CD(95) , Bcl-2, as well as copper and zinc
      levels in the peripheral blood of children with acute lymphocytic leukemia (ALL)
      prior to and 6 months after the beginning of chemotherapy. Blood parameters and
      bone marrow blast count were also assessed. Twenty of 26 patients who received
      treatment showed amelioration in apoptotic response, which is reflected in the
      elevation of CD(95) , whereas Bcl-2 protein was significantly lowered. In these
      patients, the elevated serum copper level was not significantly affected whereas
      the low serum zinc level was significantly raised. Improvement in blood
      parameters and bone marrow blast count were also achieved. Taken together, the
      data suggested that assessment of apoptosis signaling molecules might have a
      predictive impact on treatment outcome.

PMID- 21182163
TI  - Un/imaginable future selves: a discourse analysis of in-patients' talk about
      recovery from an 'eating disorder'.
AB  - BACKGROUND: The limited efficacy of treatments for eating disorders has been well
      documented. Yet few studies have explored patients' views about recovery or how
      culturally dominant ideas might be implicated in recovery or failure to recover.
      AIMS: This paper explores how 'self', 'eating disorders' and 'recovery' are
      discursively constructed in patients' accounts of their treatment experiences.
      METHOD: Semi-structured interviews were conducted with 39 participants,
      hospitalised, either in Britain or Australia, for anorexia nervosa and/or
      bulimia. Participants were asked to discuss past and present treatment
      experiences and their views on their recovery and future. Interviews were audio
      recorded, transcribed verbatim and analysed qualitatively using a discourse
      analytic methodology. RESULTS: Participants frequently construed their eating
      disorder in very negative ways whilst recovery was often positively construed as,
      for example, entailing happiness, freedom from fear and the ability to live a
      fuller life. However, many, though not all, participants also talked about
      recovery as hard or impossible to imagine for themselves. DISCUSSION: The paper
      explores how both the imagining and the seeming inability to imagine their own
      recovery can be understood in relation to participants' self-constructions and to
      culturally dominant notions of personhood and eating disorders. The implications
      of the analysis for therapeutic interventions are discussed.

PMID- 21182166
TI  - Antioxidant capacity of binuclear Cu(II)-cyclophanes, insights from two synthetic
      bioactive molecules.
AB  - The compounds 2,9,25,32-tetraoxo-4,7,27,30-tetrakis(carboxymethyl)
      1,4,7,10,24,27,30,33-octaaza-17,40-dioxa[10.1.10.1]paracyclophane and 2,9,25,32
      tetraoxo-4,7,27,30-tetrakis(carboxymethyl)-1,4,7,10,24,27,30,33
      octaaza[10.1.10.1]paracyclophane binuclear copper complexes (Cu2PO and Cu2PC,
      respectively) were studied by determining their antioxidant capacity using the
      TROLOX equivalent antioxidant capacity (TEAC) assay, and their cytotoxicity on
      cultured cells, as well as the superoxide dismutase (SOD)-like activity. Cu2PO
      had an antioxidant capacity (0.1 g eq TROLOX mol-1) within the order of magnitude
      of ascorbic acid, and both, Cu2PO and Cu2PC were nontoxic to cultured peripheral
      mononuclear blood cells. The SOD-like activity was evaluated using the nitroblue
      tetrazolium assay, and both compounds presented an excellent activity: for Cu2PO,
      the IC50 was 52 nM and for Cu2PC an IC50 of 0.5 MUM was obtained comparable to
      CuZn SOD IC50 17 nM (Fernandes et al., J Inorg Biochem 2007;101:849-858). These
      results suggest that synthetic binuclear macrocycles are good candidates to be
      used as synthetic bioactive molecules with applications in biomedicine.

PMID- 21182167
TI  - Biochemical and molecular effects of gestational and lactational coexposure to
      lead and cadmium on ovarian steroidogenesis are associated with oxidative stress
      in F1 generation rats.
AB  - Few studies have characterized the molecular and biochemical mechanisms involved
      in ovarian steroidogenesis disruption by heavy metals, such as lead and cadmium
      coexposure, on F1 generation offspring. In this study, adult pregnant female rats
      were treated subcutaneously (0.05 mg/kg of body weight per day) with sodium
      acetate (control), lead acetate, and cadmium acetate separately and in
      combination throughout gestational and lactational period, and all animals from
      each of the experimental groups were sacrificed by decapitation on postnatal day
      56 for various assays. The activities of key steroidogenic enzymes (17beta
      hydroxysteroid dehydrogenase and 3beta-hydroxysteroid dehydrogenase) decreased in
      all the metal-treated groups. But the most significant decrease in the activities
      was observed in the cadmium-treated group, whereas the combined exposure group
      showed an intermediate effect. Serum estradiol and progesterone levels were also
      significantly altered in all the metal-treated groups, with the cadmium-exposed
      group showing maximum reductions as compared with the control group. The
      inhibitory effects of lead and cadmium on ovarian steroidogenic acute regulatory
      protein (StAR) mRNA levels along with CYP11 mRNA levels were also observed.
      Ovarian cholesterol content measured also showed significant depletion in all the
      metal-treated groups, with the cadmium-exposed group showing the maximum
      depletion. The activities of ovarian enzymatic antioxidants, such as superoxide
      dismutase, catalase, and glutathione peroxidase, were all significantly
      diminished along with significant depletion in nonenzymatic antioxidants. Lipid
      peroxidation was elevated significantly in all the metal-treated groups. In
      conclusion, lead and cadmium inhibit ovarian steroidogenesis by downregulating
      StAR gene expression along with inhibiting activities of steroidogenic enzymes
      and antioxidant system.

PMID- 21182168
TI  - Protein intensity changes in the hemoglobin and plasma electrophoretic patterns
      of Oreochromis niloticus in response to single and combined Zn and Cd exposure.
AB  - The purpose of this study was to evaluate the effects of metals on the
      electrophoretic patterns of hemoglobin and blood plasma proteins of Oreochromis
      niloticus. Fish were exposed to 0.5 and 5.0 mg/L Zn, 0.1 and 1.0 mg/L Cd, and 0.5
      mg/L Zn + 0.1 mg/L Cd, and 5.0 mg/L Zn + 1.0 mg/L Cd mixtures for 7 and 28 days.
      In all concentrations tested, electrophoretic pattern of hemoglobin and plasma
      proteins by cellulose acetate electrophoresis consist of three and eight bands,
      respectively. The three bands for hemoglobin are one cathodic (Hb1) and two
      anodic (Hb2 and Hb3) bands. The protein intensity in hemoglobins of fish
      following Zn, Cd, and Zn + Cd exposures decreased in Hb1, whereas it increased in
      Hb3. The eight bands for plasma proteins are 60, 78, 87, and 94 kDA high
      molecular weight proteins (HMP) for four bands and 120, 132, 176, and 273 kDA
      very high molecular weight proteins (VHMP) for four bands. The level of 60, 78,
      and 94 kDA HMP and 120, 132, and 176 kDA VHMP increased in response to single and
      combined Zn and Cd exposure. Also, there was increasing level of the metals in
      the whole blood with increasing concentrations of metals in the exposure medium
      and with increasing duration of exposure.

PMID- 21182169
TI  - Nitric oxide in paraquat-mediated toxicity: A review.
AB  - Paraquat, a cationic herbicide, produces degenerative lesions in the lung and in
      the nervous system after systemic administration to man and animals. Many cases
      of acute poisoning and death have been reported over the past few decades.
      Although a definitive mechanism of toxicity of paraquat has not been delineated,
      a cyclic single electron reduction/oxidation is a critical mechanistic event. The
      redox cycling of paraquat has two potentially important consequences relevant to
      the development of toxicity: the generation of the superoxide anion, which can
      lead to the formation of more toxic reactive oxygen species which are highly
      reactive to cellular macromolecules; and the oxidation of reducing equivalents
      (e.g., NADPH, reduced glutathione), which results in the disruption of important
      NADPH-requiring biochemical processes necessary for normal cell function. Nitric
      oxide is an important signaling molecule that reacts with superoxide derived from
      the paraquat redox cycle, to form the potent oxidant peroxynitrite, which causes
      serious cell damage. Although nitric oxide has been involved in the mechanism of
      paraquat-mediated toxicity, the role of nitric oxide has been controversial as
      both protective and harmful effects have been described. The present review
      summarizes recent findings in the field and describes new knowledge on the role
      of nitric oxide in the paraquat-mediated toxicity.

PMID- 21182170
TI  - "What's the point?" exploring rehabilitation for people with 1 degrees  CNS
      tumours using ethnography: patients' perspectives.
AB  - BACKGROUND AND PURPOSE: Primary central nervous system (1 degrees  CNS) tumours
      represent 2% of cancers. They record the third highest mortality from cancer in
      the 18-35 age group in the UK today. Despite improving medical treatments,
      prognosis remains poor, with more patients experiencing residual complex
      functional deficits. Rehabilitation for these patients is scantily researched.
      Observational studies demonstrate improved function following inpatient and some
      outpatient multi-professional rehabilitation. Comparative recovery and functional
      improvement between patients with 1 degrees  CNS tumours and differing
      oncological and other neurological diagnoses is shown. Qualitative papers explore
      patient's values of medical treatment, demonstrating themes of hope and improved
      quality of life (QOL). No studies explore the significance of rehabilitation for
      these patients. The aim of this study was to discover the meaning of
      rehabilitation for people with this life-limiting illness through ethnographic
      enquiry.  METHODS:  Fieldwork data, primarily written narratives, field notes and
      interviews, were collected from 10 patients with 1 degrees  CNS tumours receiving
      physiotherapy at a UK specialist cancer hospital. They were asked what they
      thought the purpose of rehabilitation was in the context of their disease.
      Thematic analysis explored this data.  RESULTS:  Patient experience provided
      insightful perception of the beneficial role of rehabilitation in the context of
      their incurable disease. Main emergent themes included independence, confidence,
      'professional talk' (the broader sense of communication through talk, touch and
      therapeutic handling) and hope. An analogy presents an analytical model of the
      themes. Incidental findings identified difficulty accessing services. 
      CONCLUSION:  Rehabilitation intervention offers positive contributions to
      patients with 1 degrees  CNS tumours improving QOL irrespective of the stage of
      their disease. With equal access to cancer services, a key aim advocated in
      national directives in health-care today, it is essential that patients receiving
      treatment for this life-limiting disease have timely access to rehabilitation
      services in conjunction with holistic medical management.

PMID- 21182171
TI  - Flutter valve improves respiratory mechanics and sputum production in patients
      with bronchiectasis.
AB  - BACKGROUND AND PURPOSE: Although the application of airway clearance techniques
      is considered an important component in the treatment of several obstructive
      pulmonary diseases, there is no scientific evidence supporting the use of Flutter
      ValveTM in the management of patients with bronchiectasis. Moreover, the
      consequences of respiratory physiotherapy techniques on respiratory mechanics
      have not been fully studied. Therefore, we investigated the acute, short-term
      effects of Flutter ValveTM on respiratory mechanics and sputum production in
      bronchiectatic patients.  METHODS: EIGHT patients were evaluated in a randomized,
      blinded, cross-over trial. Impedance at 5 Hz (R5), resistance as a function of
      oscillation frequency (dR/dF), reactance at 5 Hz (X5), resonant frequency (f(0) )
      and integral of reactance between 5 Hz and resonant frequency (AX) were recorded.
      RESULTS: Flutter ValveTM cleared 8.4 mL more secretions than the Sham Flutter
      intervention (95% confidence interval [95% CI], 3.4-13.4). There was a higher
      percentage decrease in R5 (-11.2%; 95% CI, -4.4 to -18.2), dR/dF (-20.8%; 95% CI,
      -32.4 to -9) and AX (-7.8%; 95% CI, -11.9 to -3.7) under Flutter ValveTM. X5 and
      f(0) variation did not differ between interventions.  CONCLUSIONS:  Flutter
      ValveTM increases sputum removal during treatment and diminishes total and
      peripheral airway resistance in hypersecretive patients with bronchiectasis.
      Impulse oscillometry is a user-friendly tool to evaluate the effects of airway
      clearance techniques on respiratory mechanics.

PMID- 21182176
TI  - Beyond the flat world.

PMID- 21182177
TI  - On extensions of k-means clustering for automated gating of flow cytometry data.

PMID- 21182178
TI  - Rapid cell population identification in flow cytometry data.
AB  - We have developed flowMeans, a time-efficient and accurate method for automated
      identification of cell populations in flow cytometry (FCM) data based on K-means
      clustering. Unlike traditional K-means, flowMeans can identify concave cell
      populations by modelling a single population with multiple clusters. flowMeans
      uses a change point detection algorithm to determine the number of sub
      populations, enabling the method to be used in high throughput FCM data analysis
      pipelines. Our approach compares favorably to manual analysis by human experts
      and current state-of-the-art automated gating algorithms. flowMeans is freely
      available as an open source R package through Bioconductor.

PMID- 21182179
TI  - Polychromatic flow cytometry analysis of CD34+ hematopoietic stem cells in
      cryopreserved early preterm human cord blood samples.
AB  - During the last decades, extended characterizations were performed of human full
      term cord blood (hTCB) cells, but little information is available on human early
      preterm cord blood (hEPCB) hematopoietic stem cells (HSCs). In our study, we
      analyzed by flow cytometry 19 hEPCB and 17 hTCB samples. First, we observed that
      the percentage of CD34(Pos)CD45(Dim) cells was higher in hEPCB compared with hTCB
      and that it decreased during 16th-20th week of pregnancy. Within the
      CD34(Pos)CD45(Dim) population, we examined the expression of CD29, CD31, CD38,
      CD90, CD117, CD133, CD135, CD200, CD243, and CD338. We found that CD135 intensity
      and CD243(Pos) cells percentage were lower in hEPCB compared with hTCB. As to
      CD38, we observed that hEPCB samples were richer in undifferentiated
      CD34(Pos)CD45(Dim)CD38(Neg) HSCs compared with hTCB counterparts. We also
      compared the expression of the above-mentioned molecules in undifferentiated and
      committed HSCs residing in hEPCB and hTCB. In particular, although
      CD34(Pos)CD45(Dim)CD38(Pos) HSCs from both hEPCB and hTCB expressed relatively
      higher amounts of CD29, CD71, and CD135 compared with CD34(Pos)CD45(Dim)CD38(Neg)
      cells, a higher expression of CD31 was restricted to CD34(Pos)CD45(Dim)CD38(Pos)
      cells from hEPCB samples, and a higher expression of CD117 was demonstrated in
      CD34(Pos)CD45(Dim)CD38(Pos) cells from hTCB samples. Moreover, our data showed
      that CD34(Pos)CD45(Dim) cell population from hEPCB displayed higher percent of
      undifferentiated CD38(Neg)CD133(Pos) cells compared with hTCB samples. Finally,
      analyzing monocytes and lymphocytes within the two samples, we observed that T
      cell percentages were higher in hTCB, whereas B-cell percentages were higher in
      hEPCB. We, therefore, studied the B-cell lineage maturation and found a higher
      percent of pro-B and pre-B cells in hEPCB compared with hTCB samples. Taken
      together, these results evidence the hematopoietic peculiarity of hEPCB,
      potentially useful for highlighting early steps of human hematolymphopoiesis as
      well as for developing novel strategies of stem cell-based therapy.

PMID- 21182180
TI  - Quantitative characterization of preneoplastic progression using single-cell
      computed tomography and three-dimensional karyometry.
AB  - The development of morphological biosignatures to precisely characterize
      preneoplastic progression necessitates high-resolution three-dimensional (3D)
      cell imagery and robust image processing algorithms. We report on the
      quantitative characterization of nuclear structure alterations associated with
      preneoplastic progression in human esophageal epithelial cells using single-cell
      optical tomography and fully automated 3D karyometry. We stained cultured cells
      with hematoxylin and generated 3D images of individual cells by mathematically
      reconstructing 500 projection images acquired using optical absorption
      tomographic imaging. For 3D karyometry, we developed novel, fully automated
      algorithms to robustly segment the cellular, nuclear, and subnuclear components
      in the acquired cell images, and computed 41 quantitative morphological
      descriptors from these segmented volumes. In addition, we developed algorithms to
      quantify the spatial distribution and texture of the nuclear DNA. We applied our
      methods to normal, metaplastic, and dysplastic human esophageal epithelial cell
      lines, analyzing 100 cells per line. The 3D karyometric descriptors elucidated
      quantitative differences in morphology and enabled robust discrimination between
      cell lines on the basis of extracted morphological features. The morphometric
      hallmarks of cancer progression such as increased nuclear size, elevated nuclear
      content, and anomalous chromatin texture and distribution correlated with this
      preneoplastic progression model, pointing to the clinical use of our method for
      early cancer detection.

PMID- 21182181
TI  - Monitoring of intracellular nitric oxide in leishmaniasis: its applicability in
      patients with visceral leishmaniasis.
AB  - Nitric oxide (NO) has been demonstrated to be a principal effector molecule
      responsible for mediating intracellular killing of Leishmania parasites, the
      causative organism of leishmaniasis. As measurement of intracellular NO remains a
      challenge to biologists, we have developed a flow cytometric approach to perform
      real time biological detection of NO within Leishmania parasites and parasitized
      macrophages using a membrane permeable derivative of diaminofluorescein [4,5
      diaminofluorescein diacetate (DAF-2DA)]. Initially, assay optimization was
      performed in Leishmania donovani promastigotes, assay specificity being confirmed
      using both a NO donor [S-nitroso-N-acetyl-penicillamine (SNAP)] and a NO
      scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, C
      PTIO]. Using 40 MUM DAF-2DA, basal levels of intracellular NO were measured which
      varied in different Leishmania species; addition of conventional anti-leishmanial
      drugs, antimony and miltefosine translated into a dramatic increase in DAF-2T
      fluorescence. Furthermore, the assay also measured levels of NO in macrophages,
      but needed a 20 fold lower concentration of DAF-2DA, being 2 MUM. Following
      parasitization, levels of NO decreased which was normalized following treatment
      with anti-leishmanial drugs. Similarly monocytes of patients with visceral
      leishmaniasis at disease presentation showed decreased levels of NO which too
      reverted on completion of treatment. Taken together, this study opens new
      perspectives of research regarding monocyte function and provides a real time
      approach for monitoring the effect of anti-leishmanial compounds.

PMID- 21182182
TI  - Plasma-dependent, antibody- and Fcgamma receptor-mediated translocation of CD8
      molecules from T cells to monocytes.
AB  - CD8alphabeta heterodimers are mainly expressed on cytotoxic T lymphocytes. This
      study demonstrated the detection of CD8alphabeta heterodimers on human monocytes
      by whole blood erythrocyte lysis method in flow cytometry. Results revealed that
      CD8alphabeta heterodimers were not produced by monocytes themselves, but were
      transferred from T cells to monocytes when these cells were coincubated in plasma
      and with anti-CD8 monoclonal antibody (mAb). For completion of CD8 translocation
      from T cells to monocytes, cell-to-cell contact between T cells and monocytes, as
      well as binding of the Fc portion of the anti-CD8 mAb and Fcgamma receptor II
      (FcgammaRII) on monocytes were required. Furthermore, the dynamism of cell
      membrane and cytoskeleton were involved in the mechanism of CD8 translocation.
      Interestingly, CD3 and alphabetaT cell receptor (TCR) were also transferred from
      T cells to monocytes accompanied by CD8. These phenomena are consistent with Ab
      dependent and FcgammaR-mediated trogocytosis, which is recently recognized as one
      of the intercellular communication processes of the immune system. Trogocytosis
      means exchange of plasma membrane including cell surface molecules in conjugates
      formed between immune cells. Results of this study could provide another model of
      trogocytosis and clearly indicated that putative plasma factors were critically
      implicated in the mechanism of Ab-dependent and FcgammaR-mediated trogocytosis.

PMID- 21182183
TI  - Plasmonic flow cytometry by immunolabeled nanorods.
AB  - Fluorescence-based flow cytometry measures multiple cellular characteristics,
      including levels of receptor expression, by assessing the fluorescence intensity
      from a population of cells whose cell surface receptors are bound by a
      fluorescently labeled antibody or ligand for that receptor. Functionalized noble
      metal nanoparticles provide a complementary method of receptor labeling based on
      plasmonics for population analysis by flow cytometry. The potential benefits of
      using plasmonic nanoparticles to label cell surface receptors in flow cytometry
      include scattering intensity from a single particle that is equivalent to
      fluorescence intensity of 105 fluorescein molecules, biocompatibility and low
      cytotoxicity, and nonquenching optical properties. The large spectral tunability
      of nanorods also provides convenient access to plasmonic markers with peak
      surface plasmon resonances ranging from 600 to 2,200 nm, unlike gold nanosphere
      markers that are limited to visible wavelengths. Gold nanorod-based plasmonic
      flow cytometry is demonstrated herein by comparing the scattering of cells bound
      to anti-epidermal growth factor receptor (EGFR)-conjugated nanorods to the
      emission of cells bound to anti-EGFR-conjugated fluorescent labels. EGFR
      expressing cells exhibited a statistically significant six-fold increase in
      scattering when labeled with anti-EGFR-conjugated nanorods compared with labeling
      with IgG1-conjugated nanorods. Large scattering intensities were observed despite
      using a 1,000-fold lower concentration of nanorod-conjugated antibody relative to
      the fluorescently labeled antibody.

PMID- 21182184
TI  - Single-cell tracking with a reversing flow cytometer.
AB  - We have developed an instrument based on a flow cytometer platform that is
      capable of tracking individual, suspended cells over extended time periods. The
      instrument repeatedly moves in a capillary the same volume segment of fluid
      containing tens to hundreds of suspended cells through the focal point of a
      laser. Individual cells are then tracked based on the timing of when they cross
      the laser, and cell properties are measured as in a conventional flow cytometer.
      Because cells are repeatedly measured the single-cell rates of change can be
      determined. The developed instrumentation was applied to measure the variability
      of ABC transporter activity in a population of human cancer cells and the
      temperature dependence of constitutively expressed Gfp in yeast. A wide range of
      transport rates can be observed in the cancer cell population while the single
      cell Gfp fluorescence in yeast shows pronounced oscillations in response to
      temperature shifts. These observations are not detectable at the population
      level. Therefore, such measurements are useful for investigating cell function as
      they reveal how variable properties of single cells change over time.

PMID- 21182185
TI  - Heavy metal contaminants can eliminate quantum dot fluorescence.
AB  - Quantum dots (QD) are fluorescent nanocrystals that are highly useful in imaging
      and flow cytometric analyses. During routine use of monoclonal antibody
      conjugates of QD, we have occasionally seen partial or total loss of fluorescence
      when using certain lots of fixative solutions. We hypothesized that a low level
      contamination with heavy metal cations was responsible, since low level metal
      contaminants are not uncommon in formalin solutions. By titrating known
      concentrations of heavy metal cations into staining solutions, we found that
      millimolar concentrations of ferrous and zinc ions, and as low as 50 nanomolar
      cupric ions, completely eliminated QD fluorescence. By mass spectroscopic
      quantification of metals in commercial fixative solutions previously shown to
      perform poorly or well with regard to QD fluorescence, we confirmed that the
      presence of copper in solution was correlated with poor performance. Notably,
      prior addition of EDTA to chelate the divalent cations in these solutions
      prevented the inhibition of QD fluorescence. Finally, the copper-induced loss of
      QD fluorescence is irreversible: cells labeled with QD are highly fluorescent and
      can be rendered nonfluorescent by the addition of cupric sulfate, even after
      washing extensively. Indeed, these cells can then be successfully stained with
      other QD reagents, providing a method for immunofluorescence restaining of cells
      without contaminating fluorescence from the first stain.

PMID- 21182190
TI  - Morphinome--a meta-analysis applied to proteomics studies in morphine dependence.
AB  - This review is a meta-analysis of data describing proteins regulated by morphine
      influence studied worldwide across last years administration. Up to date (July
      2010), 15 studies concerning this subject have been published. Animal models,
      examined brain structures, the route of morphine administration and proteomic
      platforms used for identification of differentially expressed proteins were
      described. Standardization of obtained results allowed for creation of database
      of proteins, whose expression was altered by morphine administration
      (www.addiction-proteomics.org). Their analysis by tools available in Celera
      Panther Database was possible too. Proteins, which seem to be the most promising
      candidates for further research, due to their consistent appearance in different
      studies, were indicated. Created database may facilitate further studies by
      providing a possibility to compare results obtained during different experiments.
      At the end, dynamic picture of proteome after morphine administration, which
      emerges from the obtained results, is discussed and need for standardization of
      proteomics experiments is stressed. As meta-analysis is a very powerful tool for
      evaluation and comparison of multiple data. We believe this approach will be
      useful in the nearest future to extract vital information from a vast number of
      similar publications. Morphinome database created already by our group is a
      comfortable tool for validation and verification of new data received after
      morphine influence on proteomes investigations. It gives a chance for fast
      comparison of results without hours spent on life science literature mining.

PMID- 21182191
TI  - Fragmentation-free LC-MS can identify hundreds of proteins.
AB  - One of the most common approaches for large-scale protein identification is LC,
      followed by MS. If more than a few proteins are to be identified, the additional
      fragmentation of individual peptides has so far been considered as indispensable,
      and thus, the associated costs, in terms of instrument time and infrastructure,
      as unavoidable. Here, we present evidence to the contrary. Using a combination of
      (i) highly accurate and precise mass measurements, (ii) modern retention time
      prediction, and (iii) a robust scoring algorithm, we were able to identify 257
      proteins of Francisella tularensis from a single LC-MS experiment in a
      fragmentation-free approach (i.e. without experimental fragmentation spectra).
      This number amounts to 59% of the number of proteins identified in a standard
      fragmentation-based approach, when executed with the same false discovery rate.
      Independent evidence supports at least 27 of a set of 31 proteins that were
      identified only in the fragmentation-free approach. Our results suggest that
      additional developments in retention time prediction, measurement technology, and
      scoring algorithms may render fragmentation-free approaches an interesting
      complement or an alternative to fragmentation-based approaches.

PMID- 21182192
TI  - Quantitative protein determination for CYP induction via LC-MS/MS.
AB  - The Cytochrome P450 (CYP) proteins are a family of membrane bound proteins that
      function as a major metabolizing enzyme in the human body. Quantification of CYP
      induction is critical in determining the disposition, safety and efficacy of
      drugs in humans. Described is a gel-free, high-throughput LC-MS approach to
      quantitate the CYP isoforms 1A2, 2B6, 3A4 and 3A5 by measuring isoform specific
      peptides released by enzymatic digestion of the hepatocyte incubations. The
      method uses synthetic stable isotope-labeled peptides as internal standards and
      allows both relative and absolute quantification to be performed from hepatic
      microsomal preparations. CYP protein determined by this LC-MS method correlated
      well with the mRNA and activity for induced levels of CYP1A2, CYP2B6 and CYP3A4.
      Interestingly, a small fold change was observed for the induction of 3A5 with
      phenobarbital. The results were reproducible with an average CV less then 10% for
      repeat analysis of the sample. This LC-MS method offers a robust assay for CYP
      protein quantitation for use in CYP induction assays.

PMID- 21182193
TI  - Proteomic analysis of the anti-inflammatory action of minocycline.
AB  - Minocycline possesses anti-inflammatory properties independently of its
      antibiotic activity although the underlying molecular mechanisms are unclear.
      Lipopolysaccharide (LPS)-induced cytokines and pro-inflammatory protein
      expression are reduced by minocycline in cultured macrophages. Here, we tested a
      range of clinically important tetracycline compounds (oxytetracycline,
      doxycycline, minocycline and tigecycline) and showed that they all inhibited LPS
      induced nitric oxide production. We made the novel finding that tigecycline
      inhibited LPS-induced nitric oxide production to a greater extent than the other
      tetracycline compounds tested. To identify potential targets for minocycline, we
      assessed alterations in the macrophage proteome induced by LPS in the presence or
      absence of a minocycline pre-treatment using 2-DE and nanoLC-MS. We found a
      number of proteins, mainly involved in cellular metabolism (ATP synthase beta
      subunit and aldose reductase) or stress response (heat shock proteins), which
      were altered in expression in response to LPS, some of which were restored, at
      least in part, by minocycline. This is the first study to document proteomic
      changes induced by minocycline. The observation that minocycline inhibits some,
      but not all, of the LPS-induced proteomic changes shows that minocycline
      specifically affects some signalling pathways and does not completely inhibit
      macrophage activation.

PMID- 21182194
TI  - Iron homeostasis and responses to iron limitation in extreme acidophiles from the
      Ferroplasma genus.
AB  - Extremely acidophilic archaea from the genus Ferroplasma inhabit iron-rich
      biomining environments and are important constituents of naturally occurring
      microbial consortia that catalyze the production of acid mine drainage. A
      combined bioinformatic, transcript profiling, and proteomic approach was used to
      elucidate iron homeostasis mechanisms in "F. acidarmanus" Fer1 and F. acidiphilum
      Y(T) . Bioinformatic analysis of the "F. acidarmanus" Fer1 genome sequence
      revealed genes encoding proteins hypothesized to be involved in iron-dependent
      gene regulation and siderophore biosynthesis; the Fhu and NRAMP cation
      acquisition systems; iron storage proteins; and the SUF machinery for the
      biogenesis of Fe-S clusters. A subset of homologous genes was identified on the
      F. acidiphilum Y(T) chromosome by direct PCR probing. In both strains, some of
      the genes appeared to be regulated in a ferrous/ferric iron-dependent manner, as
      indicated by RT-PCR. A detailed gel-based proteomics analysis of responses to
      iron depletion showed that a putative isochorismatase, presumably involved in
      siderophore biosynthesis, and the SufBCD system were upregulated under iron
      limiting conditions. No evidence was obtained for iron sparing response during
      iron limitation. This study constitutes the first detailed investigation of iron
      homeostasis in extremely acidophilic archaea.

PMID- 21182195
TI  - Identification of host factors involved in coronavirus replication by
      quantitative proteomics analysis.
AB  - In this study, we applied a quantitative proteomic approach, based on SILAC, to
      investigate the interactions of coronaviruses with the secretory pathway of the
      host cell, with the aim to identify host factors involved in coronavirus
      replication. Comparison of the protein profiles of Golgi-enriched fractions of
      cells that were either mock infected or infected with mouse hepatitis virus
      revealed the significant depletion or enrichment of 116 proteins. Although
      ribosomal/nucleic acid binding proteins were enriched in the Golgi-fractions of
      mouse hepatitis virus-infected cells, proteins annotated to localize to several
      organelles of the secretory pathway were overrepresented among the proteins that
      were depleted from these fractions upon infection. We hypothesized that proteins,
      of which the abundance or distribution is affected by infection, are likely to be
      involved in the virus life cycle. Indeed, depletion of a small subset of the
      affected proteins by using small interfering RNAs identified several host factors
      involved in coronavirus infection. Transfection of small interfering RNAs
      targeting either C11orf59 or Golgi apparatus glycoprotein 1 resulted in increased
      virus replication, whereas depletion of vesicle-trafficking protein vesicle
      trafficking protein sec22b enhanced the release of infectious progeny virus.
      Overexpression of these proteins, on the other hand, had a negative effect on
      virus replication. Overall, our study shows that the SILAC approach is a suitable
      tool to study host-pathogen interactions and to identify host proteins involved
      in virus replication.

PMID- 21182196
TI  - A proteome-scale study on in vivo protein Nalpha-acetylation using an optimized
      method.
AB  - Protein N-terminal acetylation (N(alpha) -acetylation) is among the most common
      modifications in eukaryotes. We previously described a simple method to enrich
      N(alpha) -modified peptides using CNBr-activated Sepharose resin. A limitation of
      this method is that an optimal ratio of sample to resin had to be determined
      prior to the analysis since Lys-containing N(alpha) -modified peptides may be
      lost. To address this problem, we hereby present an optimized method by the
      introduction of double incubation at pH 6.0. We demonstrate with the optimized
      method that the N(alpha) -modified peptides can be enriched regardless of whether
      epsilon-NH(2) is present or not, and the sample to resin ratio optimization is no
      longer necessary. Another improvement was accomplished by the inclusion of the
      singly charged precursor for MS/MS fragmentation to alleviate the shortcoming of
      the reduced charge state of N(alpha) -modified peptides. We employed a duplicate
      experiment using 80 MUg samples each and identified 922 IPI annotated and 103 IPI
      unannotated acetylated N-termini from 989 proteins, so far the largest acetylated
      N-termini data set acquired from a tryptic digest. Furthermore, the
      reproducibility of the N(alpha) -acetyl proteome approach was evaluated and its
      complementarity to the regular proteome approach was analyzed. The unexpected
      coupling of CNBr-activated Sepharose to His-containing peptides via the imidazole
      group was discovered.

PMID- 21182197
TI  - Peripheral profiling analysis for bipolar disorder reveals markers associated
      with reduced cell survival.
AB  - Little is known about the molecular factors that are altered in remitting bipolar
      disorder (BD) patients. We carried out proteome profiling of peripheral blood
      mononuclear cells (PBMCs) and serum from BD patients who were not experiencing
      mania or major depression (euthymia) compared to matched healthy controls using
      liquid chromatography-mass spectrometry (LC-MS(E) ) and Multi-Analyte Profiling
      (Human Map((r)) ) platforms. This resulted in the identification of approximately
      60 differentially expressed molecules involved predominantly in cell
      death/survival pathways. In PBMCs, this was manifested in cytoskeletal and stress
      response-associated proteins, whereas most serum analytes were associated with
      the inflammatory response. The predicted effect of serum analytes on
      physiological systems was tested by treating PBMCs with serum obtained from the
      same patients, resulting in reduced cellular survival. These preliminary results
      suggest that BD patients carry a peripheral fingerprint that has detrimental
      effects on cell function and that could be used to distinguish BD patients from
      healthy controls despite being in a remission phase. It is hoped that additional
      studies of BD patients in the manic and depressed stages could lead to the
      identification of a molecular fingerprint that could be used for predicting
      episodic switching and for guiding treatment strategies.

PMID- 21182199
TI  - Proteomic analysis of the maize rachis: potential roles of constitutive and
      induced proteins in resistance to Aspergillus flavus infection and aflatoxin
      accumulation.
AB  - Infection of the maize (Zea mays L.) with aflatoxigenic fungus Aspergillus flavus
      and consequent contamination with carcinogenic aflatoxin is a persistent and
      serious agricultural problem causing disease and significant crop losses
      worldwide. The rachis (cob) is an important structure of maize ear that delivers
      essential nutrients to the developing kernels and A. flavus spreads through the
      rachis to infect kernels within the ear. Therefore, rachis plays an important
      role in fungal proliferation and subsequent kernel contamination. We used
      proteomic approaches and investigated the rachis tissue from aflatoxin
      accumulation resistant (Mp313E and Mp420) and susceptible (B73 and SC212m) maize
      inbred lines. First, we compared rachis proteins from resistant and susceptible
      inbred lines, which revealed that the young resistant rachis contains higher
      levels of abiotic stress-related proteins and proteins from phenylpropanoid
      metabolism, whereas susceptible young rachis contains pathogenesis-related
      proteins, which are generally inducible upon biotic stress. Second, we identified
      A. flavus-responsive proteins in rachis of both resistant and susceptible
      genotypes after 10- and 35-day infection. Differential expression of many
      stress/defense proteins during rachis juvenility, maturation and after A. flavus
      challenge demonstrates that resistant rachis relies on constitutive defenses,
      while susceptible rachis is more dependent on inducible defenses.

PMID- 21182198
TI  - Examining serum amyloid P component microheterogeneity using capillary
      isoelectric focusing and MALDI-MS.
AB  - Serum amyloid P component (SAP) is a glycoprotein of interest due to its presence
      in amyloid plaque formations. As with most glycoproteins, SAP can possibly vary
      greatly in its isoforms, which can be an important factor toward understanding
      the role of SAP. Interestingly, previous characterizations suggest varying
      degrees of microheterogeneity, some of which are in conflict. In this work, we
      provide new information to clarify SAP's microheterogeneity profile using CIEF to
      carefully analyze pooled samples and by studying individual samples across
      populations with mass spectrometric immunoassay. With respect to CIEF, a single
      pI band was observed suggesting that human SAP does not have extensive
      heterogeneity concluded from gel IEF experiments in the past. Additionally, this
      is supported by a population study, which revealed an overwhelming degree of
      uniformity. Overall, this work corroborates the idea that SAP is relatively
      consistent across the population and with respect to microheterogeneity.

PMID- 21182200
TI  - Combining peptide recognition specificity and context information for the
      prediction of the 14-3-3-mediated interactome in S. cerevisiae and H. sapiens.
AB  - Large-scale interaction studies contribute the largest fraction of protein
      interactions information in databases. However, co-purification of non-specific
      or indirect ligands, often results in data sets that are affected by a
      considerable number of false positives. For the fraction of interactions mediated
      by short linear peptides, we present here a combined experimental and
      computational strategy for ranking the reliability of the inferred partners. We
      apply this strategy to the family of 14-3-3 domains. We have first characterized
      the recognition specificity of this domain family, largely confirming the results
      of previous analyses, while revealing new features of the preferred sequence
      context of 14-3-3 phospho-peptide partners. Notably, a proline next to the
      carboxy side of the phospho-amino acid functions as a potent inhibitor of 14-3-3
      binding. The position-specific information about residue preference was encoded
      in a scoring matrix and two regular expressions. The integration of these three
      features in a single predictive model outperforms publicly available prediction
      tools. Next we have combined, by a naive Bayesian approach, these "peptide
      features" with "protein features", such as protein co-expression and co
      localization. Our approach provides an orthogonal reliability assessment and maps
      with high confidence the 14-3-3 peptide target on the partner proteins.

PMID- 21182201
TI  - Proteomic analysis of egg white proteins during storage.
AB  - Egg storage causes egg white to lose its viscous nature to form a thin liquid,
      commonly referred to as egg white thinning. To understand the mechanisms
      underlying egg white thinning, white-shell eggs were used in the present study to
      determine the proteome-level changes of egg white proteins occurred during
      storage. Egg white thinning was observed visually after 20 days of storage at
      ambient temperature (22 +/- 2  degrees C) when the maximum number of proteome
      level changes occurred. The proteins that showed significant changes in abundance
      during storage included ovalbumin, clusterin, ovoinhibitor, ovotransferrin, and
      prostaglandin D2 synthase. Among these, only the abundance of clusterin was
      observed to change continuously during the storage period. Hence, it is expected
      that the increase in the concentrations of clusterin and ovoinhibitor along with
      the change of ovalbumin content during storage might contribute to egg white
      thinning. Degradation of ovalbumin/clusterin during egg storage may be due to the
      combined effect of proteolysis and increase in pH; this may also be partly
      responsible for egg white thinning phenomenon.

PMID- 21182202
TI  - The Protein Information and Property Explorer 2: gaggle-like exploration of
      biological proteomic data within one webpage.
AB  - The Protein Information and Property Explorer 2 (PIPE2) is an enhanced software
      program and updated web application that aims at providing the proteomic
      researcher a simple, intuitive user interface through which to begin inquiry into
      the biological significance of a list of proteins typically produced by MS/MS
      proteomic processing software. PIPE2 includes an improved interface, new data
      visualization options, and new data analysis methods for combining disparate, but
      related, data sets. In particular, PIPE2 has been enhanced to handle multi
      dimensional data such as protein abundance, gene expression, and/or interaction
      data. The current architecture of PIPE2, modeled after that of Gaggle (a
      programming infrastructure for interoperability between separately developed
      software tools), contains independent functional units that can be instantiated
      and pieced together at the user's discretion to form a pipelined analysis
      workflow. Among these functional units is the Network Viewer component, which
      adds rich network analysis capabilities to the suite of existing proteomic web
      resources. Additionally, PIPE2 implements a framework within which new analysis
      procedures can be easily deployed and distributed over the World Wide Web. PIPE2
      is available as a web service at http://pipe2.systemsbiology.net/.

PMID- 21182203
TI  - A large set of estrogen receptor beta-interacting proteins identified by tandem
      affinity purification in hormone-responsive human breast cancer cell nuclei.
AB  - Estrogen receptors alpha (ER-alpha) and beta (ER-beta) play distinct biological
      roles in onset and progression of hormone-responsive breast cancer, with ER-beta
      exerting a modulatory activity on ER-alpha-mediated estrogen signaling and
      stimulation of cell proliferation by mechanisms still not fully understood. We
      stably expressed human ER-beta fused to a tandem affinity purification-tag in
      estrogen-responsive MCF-7 cells and applied tandem affinity purification and
      nanoLC-MS/MS to identify the ER-beta interactome of this cell type. Functional
      annotation by bioinformatics analyses of the 303 proteins that co-purify with ER
      beta from nuclear extracts identify several new molecular partners of this
      receptor subtype that represents nodal points of a large protein network
      controlling multiple processes and functions in breast cancer cells.

PMID- 21182204
TI  - Shotgun proteomic profiling of five species of New Zealand Pachycladon.

PMID- 21182205
TI  - Identification of proteins associated with ligand-activated estrogen receptor
      alpha in human breast cancer cell nuclei by tandem affinity purification and nano
      LC-MS/MS.
AB  - Estrogen receptor alpha (ER-alpha) is a key mediator of estrogen actions in
      breast cancer (BC) cells. Understanding the effects of ligand-activated ER-alpha
      in target cells requires identification of the molecular partners acting in
      concert with this nuclear receptor to transduce the hormonal signal. We applied
      tandem affinity purification (TAP), glycerol gradient centrifugation and MS
      analysis to isolate and identify proteins interacting with ligand-activated ER
      alpha in MCF-7 cell nuclei. This led to the identification of 264 ER-associated
      proteins, whose functions highlight the hinge role of ER-alpha in the
      coordination of multiple hormone-regulated nuclear processes in BC cells.

PMID- 21182206
TI  - Low CD38 expression in lymphoblastoid cells and haplotypes are both associated
      with autism in a family-based study.
AB  - BACKGROUND: Impairments in social processes characterize one of the core deficits
      in autism spectrum disorders (ASD) and accumulating evidence suggests that
      oxytocin neurotransmission is implicated in mediating social adaptation in ASD.
      Using a mouse model, CD38, a transmembrane protein expressed in immune cells but
      also in brain, was found to be critical for social behavior via regulation of
      oxytocin secretion. This prompted us to both examine CD38 expression in human
      lymphoblastoid cell lines (LBC) as well as to test association between SNPs
      across the CD38 gene and ASD. METHODS: LBC's were derived from 44 ASD lines and
      40 "unaffected" parents. Family-based association (UNPHASED) was examined by
      genotyping 11 tagging SNPs spanning the CD38 gene identified using HapMap data in
      170 trios. An additional SNP (rs3796863) associated in a study by Munesue et al.
      with ASD was also genotyped. RESULTS: A highly significant reduction in CD38
      expression was observed in immortalized lymphocytes derived from ASD subjects
      compared to their "unaffected" parents (F517.2, P50.00024, df51). Haplotype
      analysis showed significant association (permutation corrected) between three and
      seven locus haplotypes and DSM IV ASD in low functioning (IQ < 70) subjects.
      CONCLUSIONS: The current report supports a role for CD38 in conferring risk for
      ASD. Notably, our study shows that this gene is not only associated with low
      functioning ASD but that CD38 expression is markedly reduced in LBC derived from
      ASD subjects compared to "unaffected" parents, strengthening the connection
      between oxytocin and ASD.

PMID- 21182208
TI  - Conversational gestures in autism spectrum disorders: asynchrony but not
      decreased frequency.
AB  - Conversational or "co-speech" gestures play an important role in communication,
      facilitating turntaking, providing visuospatial information, clarifying
      subtleties of emphasis, and other pragmatic cues. Consistent with other pragmatic
      language deficits, individuals with autism spectrum disorders (ASD) are said to
      produce fewer conversational gestures, as specified in many diagnostic measures.
      Surprisingly, while research shows fewer deictic gestures in young children with
      ASD, there is a little empirical evidence addressing other forms of gesture. The
      discrepancy between clinical and empirical observations may reflect impairments
      unrelated to frequency, such as gesture quality or integration with speech.
      Adolescents with high-functioning ASD (n = 15), matched on age, gender, and IQ to
      15 typically developing (TD) adolescents, completed a narrative task to assess
      the spontaneous production of speech and gesture. Naive observers rated the
      stories for communicative quality. Overall, the ASD group's stories were rated as
      less clear and engaging. Although utterance and gesture rates were comparable,
      the ASD group's gestures were less closely synchronized with the co-occurring
      speech, relative to control participants. This gesture-speech synchrony
      specifically impacted communicative quality across participants. Furthermore,
      while story ratings were associated with gesture count in TD adolescents, no such
      relationship was observed in adolescents with ASD, suggesting that gestures do
      not amplify communication in this population. Quality ratings were, however,
      correlated with ASD symptom severity scores, such that participants with fewer
      ASD symptoms were rated as telling higher quality stories. Implications of these
      findings are discussed in terms of communication and neuropsychological
      functioning in ASD.

PMID- 21182209
TI  - Neonatally measured immunoglobulins and risk of autism.
AB  - Previous studies indicate that prenatal exposure to infections is a possible
      pathway through which autism spectrum disorders (ASD) could be initiated. We
      investigated whether immunoglobulin levels in archived specimens obtained from
      newborns subsequently diagnosed with ASD are different from levels in newborn
      specimens from controls. Children with ASD born in six California counties in
      1994 were ascertained through records of the California Department of
      Developmental Services (DDS) and Kaiser Permanente; controls were randomly
      selected using birth certificates. Archived newborn blood specimens were obtained
      from the California Genetic Disease Screening Program (GDSP) for N = 213 cases
      and N = 265 controls and assayed to determine levels of total IgG, antigen
      specific IgG to selected common pathogens, total IgM, total IgA, and C-reactive
      protein (CRP). We did not find measurable levels of total IgM or IgA in any
      neonate and measurable CRP was present in only a few. No antigen-specific IgG
      antibodies were elevated in cases compared to controls and total IgG levels were
      lower. In adjusted models, a 10-unit increase in total IgG yielded an OR = 0.72
      (95% CI 0.56, 0.91); a significantly decreasing trend in risk of ASD was observed
      across increasing exposure quartiles of total IgG (P = 0.01). The finding of
      lower IgG in cases may indicate maternal immune dysfunction during gestation
      and/or impaired transplacental transfer of immunoglobulins. Further investigation
      of IgG levels in newborns and the mechanisms by which they might be associated
      with ASD are warranted.

PMID- 21182207
TI  - Variants in several genomic regions associated with asperger disorder.
AB  - Asperger disorder (ASP) is one of the autism spectrum disorders (ASD) and is
      differentiated from autism largely on the absence of clinically significant
      cognitive and language delays. Analysis of a homogenous subset of families with
      ASP may help to address the corresponding effect of genetic heterogeneity on
      identifying ASD genetic risk factors. To examine the hypothesis that common
      variation is important in ASD, we performed a genome-wide association study
      (GWAS) in 124 ASP families in a discovery data set and 110 ASP families in a
      validation data set. We prioritized the top 100 association results from both
      cohorts by employing a ranking strategy. Novel regions on 5q21.1 (P = 9.7 * 10(
      7) ) and 15q22.1-q22.2 (P = 7.3 * 10(-6) ) were our most significant findings in
      the combined data set. Three chromosomal regions showing association, 3p14.2 (P =
      3.6 * 10(-6) ), 3q25-26 (P = 6.0 * 10(-5) ) and 3p23 (P = 3.3 * 10(-4) )
      overlapped linkage regions reported in Finnish ASP families, and eight
      association regions overlapped ASD linkage areas. Our findings suggest that ASP
      shares both ASD-related genetic risk factors, as well as has genetic risk factors
      unique to the ASP phenotype.

PMID- 21182210
TI  - Lack of association between markers in the ITGA3, ITGAV, ITGA6 and ITGB3 and
      autism in an Irish sample.
AB  - Autism is a neurodevelopmental disorder characterized by impairments in three
      core areas--language, social interaction and restricted/repetitive behaviours. It
      is generally accepted that genetics plays a large role in the aetiology of
      autism, but the exact mechanism is still unknown. We recently published evidence
      of an association between autism and the ITGA4 gene [Conroy et al., 2008]. Two
      genomic regions have shown evidence of linkage to autism in multiple studies-
      2q31-q33 and 17q21-q22. Both of these regions harbour multiple integrin subunit
      genes. We tested markers in ITGA3, ITGA6, ITGAV and ITGB3 for association with
      autism in the Irish autism sample. No markers in ITGA3, ITGA6, ITGAV and ITGB3
      were found to be associated with autism. Three 3-marker haplotypes in ITGAV,
      ITGA3 and ITGA6 were found to be nominally associated (0.01 < P < 0.05) and to
      have unremarkable findings. Our data indicates that in the Irish autism sample
      the integrin genes tested here do not play an important role in the aetiology of
      autism.

PMID- 21182211
TI  - Face processing abilities in relatives of individuals with ASD.
AB  - Individuals with an autism spectrum disorder (ASD) show difficulties identifying
      familiar faces, recognizing emotional expressions and judging eye-gaze direction.
      Recent research suggests that relatives of individuals with AS also show
      impairments in some aspects of face processing but no study has comprehensively
      assessed the nature and extent of face-processing difficulties in a group of
      relatives. This study compared the performance of 22 parents/adult siblings of
      individuals with ASD ("relatives" group), 26 adults with ASD, and 26 typically
      developing adults on tasks of face discrimination, facial expression recognition
      and judging eye-gaze direction. Relatives of individuals with ASD were less able
      to discriminate subtle differences between faces than typically developing
      adults, but were more sensitive to such differences than adults with ASD.
      Furthermore, relatives were significantly worse at identifying expressions of
      fear and disgust than typically developing adults and failed to show the typical
      sensitivity to direct compared with averted eye-gaze direction--a strikingly
      similar pattern to that observed in adults with ASD. These findings show that
      atypical patterns of face processing are found in some relatives of individuals
      with ASD and suggest that these difficulties may represent a cognitive
      endophenotype.

PMID- 21182214
TI  - Compositional studies of human RPE lipofuscin: mechanisms of molecular
      modifications.
AB  - The accumulation of lipofuscin has previously been implicated in several retinal
      diseases including Best's macular dystrophy, Stargardt's disease and age-related
      macular degeneration (AMD). Previously one of the major fluorophores of
      lipofuscin was identified as a bis-retinoid pyridinium salt called A2E, which is
      known to photochemically cause damage. In addition to A2E, there are numerous
      components in RPE lipofuscin that are unidentified. These compounds were
      determined to be structurally related to A2E by their fragmentation pattern with
      losses of 106, 190, 174 and/or 150 amu from the parent ion and the formation of
      fragments of ca 592 amu. The vast majority consists of relatively hydrophobic
      components corresponding to derivatized A2E with molecular weights in discrete
      groups of 800-900, 970-1080 and > 1200 m/z regions. In order to determine the
      mechanism of these modifications, A2E was chemically modified by; (1) the
      formation of specific esters, (2) reaction with specific aldehydes and (3)
      spontaneous auto-oxidation. The contribution of ester formation to the naturally
      occurring components of lipofuscin was discounted since their fragmentation
      patterns were different to those found in vivo. Alternatively, reactions with
      specific aldehydes result in nearly identical products as those found in vivo.
      Artificial aging of RPE lipofuscin gives a complex mixture of structurally
      related components. This results from the auto- and/or photooxidation of A2E to
      form aldehydes, which then back react with A2E giving a series of higher
      molecular weight products. The majority of these modifications result in
      compounds that are much more hydrophobic than A2E. These higher molecular weight
      materials have increased values of log P compared to A2E. This increase in
      hydrophobicity most likely aids in the sequestering of A2E into granules with the
      concomitant diminution of its reactivity. Therefore, these processes may serve as
      protective mechanisms for the RPE.

PMID- 21182212
TI  - Atypical diffusion tensor hemispheric asymmetry in autism.
AB  - BACKGROUND: Biological measurements that distinguish individuals with autism from
      typically developing individuals and those with other developmental and
      neuropsychiatric disorders must demonstrate very high performance to have
      clinical value as potential imaging biomarkers. We hypothesized that further
      study of white matter microstructure (WMM) in the superior temporal gyrus (STG)
      and temporal stem (TS), two brain regions in the temporal lobe containing
      circuitry central to language, emotion, and social cognition, would identify a
      useful combination of classification features and further understand autism
      neuropathology. METHODS: WMM measurements from the STG and TS were examined from
      30 high-functioning males satisfying full criteria for idiopathic autism aged 7
      28 years and 30 matched controls and a replication sample of 12 males with
      idiopathic autism and 7 matched controls who participated in a previous case
      control diffusion tensor imaging (DTI) study. Language functioning, adaptive
      functioning, and psychotropic medication usage were also examined. RESULTS: In
      the STG, we find reversed hemispheric asymmetry of two separable measures of
      directional diffusion coherence, tensor skewness, and fractional anisotropy. In
      autism, tensor skewness is greater on the right and fractional anisotropy is
      decreased on the left. We also find increased diffusion parallel to white matter
      fibers bilaterally. In the right not left TS, we find increased omnidirectional,
      parallel, and perpendicular diffusion. These six multivariate measurements
      possess very high ability to discriminate individuals with autism from
      individuals without autism with 94% sensitivity, 90% specificity, and 92%
      accuracy in our original and replication samples. We also report a near
      significant association between the classifier and a quantitative trait index of
      autism and significant correlations between two classifier components and
      measures of language, IQ, and adaptive functioning in autism.

PMID- 21182215
TI  - A study of characteristic fragmentation of isoflavonoids by using negative ion
      ESI-MSn.
AB  - Isoflavone mono-O-glycosides were investigated by electrospray ionization tandem
      mass spectrometry with a quadrupole linear ion trap mass spectrometer in negative
      ion mode. Isoflavonoids having different positions of glycosylation or
      methylation were differentiated according to the relative abundances of Y(0)(-)
      and [Y(0)-H](-*) ions generated from the [M-H](-) ion. It is found that the site
      of glycosyl or methyl group significantly affects relative abundances of the
      Y(0)(-) and [Y(0)-H](-*) ions. In addition, the characteristic ion [Y(0)-2H](-)
      was observed in the product ion spectrum of genistein 7-O-beta-D-glucoside and
      was also detected, together with the [Y(0)-CH(3)](-*) and [Y(0)-H-CH(3)](-) ions
      in the product ion spectra of glycitin and 6-methoxy genistein 7-O-beta-D
      glucoside. The structures of isoflavonoids can be characterized and identified
      according to the formation of these diagnostic ions. The results obtained from
      this investigation can promote the rapid identification of isoflavonoids in crude
      plant extracts.

PMID- 21182218
TI  - Hepatic organ protection: from basic science to clinical practice.
AB  - Hepatic ischemia and reperfusion (I/R) injury during liver surgery is still the
      main cause of postoperative liver failure and the subsequent rise of mortality in
      these patients. During the last few years, a multitude of underlying mechanisms
      have been extensively characterized and many different protective approaches have
      been evaluated under experimental conditions. Some of them have already found
      their way into small sized clinical trials. In this Topic Highlight series of
      articles, we present recent insights into promising protective concepts including
      the regulation and optimization of hepatic blood flow, molecular mechanisms of
      preconditioning and pharmacological approaches with the aim of limiting hepatic
      I/R injury. Leading international experts present the latest experimental
      evidence in their fields stressing clinically relevant ideas, which are now on
      the edge of entering clinical practice.

PMID- 21182217
TI  - Oxidative stress and antioxidants in hepatic pathogenesis.
AB  - Long term hepatitis B virus (HBV) infection is a major risk factor in
      pathogenesis of chronic liver diseases, including hepatocellular carcinoma (HCC).
      The HBV encoded proteins, hepatitis B virus X protein and preS, appear to
      contribute importantly to the pathogenesis of HCC. Both are associated with
      oxidative stress, which can damage cellular molecules like lipids, proteins, and
      DNA during chronic infection. Chronic alcohol use is another important factor
      that contributes to oxidative stress in the liver. Previous studies reported that
      treatment with antioxidants, such as curcumin, silymarin, green tea, and vitamins
      C and E, can protect DNA from damage and regulate liver pathogenesis-related
      cascades by reducing reactive oxygen species. This review summarizes some of the
      relationships between oxidative stress and liver pathogenesis, focusing upon HBV
      and alcohol, and suggests antioxidant therapeutic approaches.

PMID- 21182219
TI  - Regulation of hepatic blood flow: the hepatic arterial buffer response revisited.
AB  - The interest in the liver dates back to ancient times when it was considered to
      be the seat of life processes. The liver is indeed essential to life, not only
      due to its complex functions in biosynthesis, metabolism and clearance, but also
      its dramatic role as the blood volume reservoir. Among parenchymal organs, blood
      flow to the liver is unique due to the dual supply from the portal vein and the
      hepatic artery. Knowledge of the mutual communication of both the hepatic artery
      and the portal vein is essential to understand hepatic physiology and
      pathophysiology. To distinguish the individual importance of each of these
      inflows in normal and abnormal states is still a challenging task and the subject
      of ongoing research. A central mechanism that controls and allows constancy of
      hepatic blood flow is the hepatic arterial buffer response. The current paper
      reviews the relevance of this intimate hepatic blood flow regulatory system in
      health and disease. We exclusively focus on the endogenous interrelationship
      between the hepatic arterial and portal venous inflow circuits in liver resection
      and transplantation, as well as inflammatory and chronic liver diseases. We do
      not consider the hepatic microvascular anatomy, as this has been the subject of
      another recent review.

PMID- 21182220
TI  - Molecular mechanisms of liver preconditioning.
AB  - Ischemia/reperfusion (I/R) injury still represents an important cause of
      morbidity following hepatic surgery and limits the use of marginal livers in
      hepatic transplantation. Transient blood flow interruption followed by
      reperfusion protects tissues against damage induced by subsequent I/R. This
      process known as ischemic preconditioning (IP) depends upon intrinsic
      cytoprotective systems whose activation can inhibit the progression of
      irreversible tissue damage. Compared to other organs, liver IP has additional
      features as it reduces inflammation and promotes hepatic regeneration. Our
      present understanding of the molecular mechanisms involved in liver IP is still
      largely incomplete. Experimental studies have shown that the protective effects
      of liver IP are triggered by the release of adenosine and nitric oxide and the
      subsequent activation of signal networks involving protein kinases such as
      phosphatidylinositol 3-kinase, protein kinase C delta/epsilon and p38 MAP kinase,
      and transcription factors such as signal transducer and activator of
      transcription 3, nuclear factor-kappaB and hypoxia-inducible factor 1. This
      article offers an overview of the molecular events underlying the preconditioning
      effects in the liver and points to the possibility of developing pharmacological
      approaches aimed at activating the intrinsic protective systems in patients
      undergoing liver surgery.

PMID- 21182221
TI  - Heme oxygenase system in hepatic ischemia-reperfusion injury.
AB  - Hepatic ischemia-reperfusion injury (IRI) limits access to transplantation. Heme
      oxygenase-1 (HO-1) is a powerful antioxidant enzyme which degrades free heme into
      biliverdin, free iron and carbon monoxide. HO-1 and its metabolites have the
      ability to modulate a wide variety of inflammatory disorders including hepatic
      IRI. Mechanisms of this protective effect include reduction of oxygen free
      radicals, alteration of macrophage and T cell phenotype. Further work is required
      to understand the physiological importance of the many actions of HO-1 identified
      experimentally, and to harness the protective effect of HO-1 for therapeutic
      potential.

PMID- 21182222
TI  - Role of nitric oxide in hepatic ischemia-reperfusion injury.
AB  - Hepatic ischemia-reperfusion injury (IRI) occurs upon restoration of hepatic
      blood flow after a period of ischemia. Decreased endogenous nitric oxide (NO)
      production resulting in capillary luminal narrowing is central in the
      pathogenesis of IRI. Exogenous NO has emerged as a potential therapy for IRI
      based on its role in decreasing oxidative stress, cytokine release, leukocyte
      endothelial-adhesion and hepatic apoptosis. This review will highlight the
      influence of endogenous NO on hepatic IRI, role of inhaled NO in ameliorating
      IRI, modes of delivery, donor drugs and potential side effects of exogenous NO.

PMID- 21182224
TI  - Current protective strategies in liver surgery.
AB  - During liver resection surgery for cancer or liver transplantation, the liver is
      subject to ischaemia (reduction in blood flow) followed by reperfusion
      (restoration of blood flow), which results in liver injury [ischemia-reperfusion
      (IR) or IR injury]. Modulation of IR injury can be achieved in various ways.
      These include hypothermia, ischaemic preconditioning (IPC) (brief cycles of
      ischaemia followed by reperfusion of the organ before the prolonged period of
      ischaemia i.e. a conditioning response), ischaemic postconditioning (conditioning
      after the prolonged period of ischaemia but before the reperfusion),
      pharmacological agents to decrease IR injury, genetic modulation of IR injury,
      and machine perfusion (pulsatile perfusion). Hypothermia decreases the metabolic
      functions and the oxygen consumption of organs. Static cold storage in University
      of Wisconsin solution reduces IR injury and has prolonged organ storage and
      improved the function of transplanted grafts. There is currently no evidence for
      any clinical advantage in the use of alternate solutions for static cold storage.
      Although experimental data from animal models suggest that IPC, ischaemic
      postconditioning, various pharmacological agents, gene therapy, and machine
      perfusion decrease IR injury, none of these interventions can be recommended in
      clinical practice. This is because of the lack of randomized controlled trials
      assessing the safety and efficacy of ischaemic postconditioning, gene therapy,
      and machine perfusion. Randomized controlled trials and systematic reviews of
      randomized controlled trials assessing the safety and efficacy of IPC and various
      pharmacological agents have demonstrated biochemical or histological improvements
      but this has not translated to clinical benefit. Further well designed randomized
      controlled trials are necessary to assess the various new protective strategies
      in liver resection.

PMID- 21182225
TI  - Promoter polymorphism of MRP1 associated with reduced survival in hepatocellular
      carcinoma.
AB  - AIM: to investigate the effect of the G-1666A polymorphism in the multidrug
      resistance related protein-1 (MRP1) on outcome of hepatocellular carcinoma (HCC).
      METHODS: a cohort of 162 patients with surgically resected HCC who received no
      postsurgical treatment until relapse was studied. Genotyping was performed by
      polymerase chain reaction-restriction fragment length polymorphism analysis.
      Electrophoretic mobility shift assay (EMSA) was used to evaluate the influence of
      the G-1666A polymorphism on the binding affinity of the MRP1 promoter with its
      putative transcription factors. RESULTS: Kaplan-Meier analysis showed that
      patients with GG homologues had a reduced 4-year disease-free survival compared
      with those carrying at least one A allele (P = 0.011). Multivariate Cox
      regression analysis indicated that the -1666GG genotype represented an
      independent predictor of poorer disease-free survival [hazard ratio (HR) = 3.067,
      95% confidence interval (CI): 1.587-5.952, P = 0.001], and this trend became
      worse in men (HR = 3.154, 95% CI: 1.604-6.201, P = 0.001). A similar association
      was also observed between 4-year overall survival and the polymorphism in men (HR
      = 3.342, 95% CI: 1.474-7.576, P = 0.004). Moreover, EMSA suggested that the G
      allele had a stronger binding affinity to nuclear proteins. CONCLUSION: the MRP1 
      1666GG genotype predicted a worse outcome and was an independent predictor of
      poor survival in patients with HCC from Southeast China.

PMID- 21182223
TI  - Hepatoprotective actions of melatonin: possible mediation by melatonin receptors.
AB  - Melatonin, the hormone of darkness and messenger of the photoperiod, is also well
      known to exhibit strong direct and indirect antioxidant properties. Melatonin has
      previously been demonstrated to be a powerful organ protective substance in
      numerous models of injury; these beneficial effects have been attributed to the
      hormone's intense radical scavenging capacity. The present report reviews the
      hepatoprotective potential of the pineal hormone in various models of oxidative
      stress in vivo, and summarizes the extensive literature showing that melatonin
      may be a suitable experimental substance to reduce liver damage after sepsis,
      hemorrhagic shock, ischemia/reperfusion, and in numerous models of toxic liver
      injury. Melatonin's influence on hepatic antioxidant enzymes and other
      potentially relevant pathways, such as nitric oxide signaling, hepatic cytokine
      and heat shock protein expression, are evaluated. Based on recent literature
      demonstrating the functional relevance of melatonin receptor activation for
      hepatic organ protection, this article finally suggests that melatonin receptors
      could mediate the hepatoprotective actions of melatonin therapy.

PMID- 21182226
TI  - Impaired PI3K/Akt signal pathway and hepatocellular injury in high-fat fed rats.
AB  - AIM: to determine whether mitochondrial dysfunction resulting from high-fat diet
      is related to impairment of the phosphatidylinositol 3-kinase (PI3K)/protein
      kinase B (Akt, also known as PKB) pathway. METHODS: rat models of nonalcoholic
      fatty liver were established by high-fat diet feeding. The expression of total
      and phosphorylated P13K and Akt proteins in hepatocytes was determined by Western
      blotting. Degree of fat accumulation in liver was measured by hepatic
      triglyceride. Mitochondrial number and size were determined using quantitative
      morphometric analysis under transmission electron microscope. The permeability of
      the outer mitochondrial membrane was assessed by determining the potential
      gradient across this membrane. RESULTS: after Wistar rats were fed with high-fat
      diet for 16 wk, their hepatocytes displayed an accumulation of fat (103.1 +/-
      12.6 vs 421.5 +/- 19.7, P < 0.01), deformed mitochondria (9.0% +/- 4.3% vs 83.0%
      +/- 10.9%, P < 0.05), and a reduction in the mitochondrial membrane potential
      (389.385% +/- 18.612% vs 249.121% +/- 13.526%, P < 0.05). In addition, the
      expression of the phosphorylated P13K and Akt proteins in hepatocytes was
      reduced, as was the expression of the anti-apoptotic protein Bcl-2, while
      expression of the pro-apoptotic protein caspase-3 was increased. When animals
      were treated with pharmacological inhibitors of P13K or Akt, instead of high-fat
      diet, a similar pattern of hepatocellular fat accumulation, mitochondrial
      impairment, and change in the levels of PI3K, Akt, Bcl-2 was observed.
      CONCLUSION: high-fat diet appears to inhibit the PI3K/Akt signaling pathway,
      which may lead to hepatocellular injury through activation of the mitochondrial
      membrane pathway of apoptosis.

PMID- 21182227
TI  - High prevalence of nonalcoholic fatty liver in patients with idiopathic venous
      thromboembolism.
AB  - AIM: to assess the prevalence of nonalcoholic fatty liver disease (NAFLD) in
      patients with idiopathic venous thromboembolism (VTE). METHODS: in a case-control
      study, after excluding subjects with well-consolidated risk factors for VTE,
      idiopathic VTE was documented in 138 consecutive patients who were referred to
      our department. Two hundred and seventy-six healthy sex/age/body-mass-index
      matched subjects, without any clinical/instrumental evidence of VTE, served as
      controls. All underwent a clinical/laboratory/ultrasound assessment for the
      presence of metabolic syndrome and NAFLD. RESULTS: NAFLD was detected in 112/138
      cases (81%) and in 84/276 controls (30%) [risk ratio: 2.7, 95% confidence
      interval (CI): 2.2-3.2, P < 0.0001]. Metabolic syndrome and smoking habit were
      more prevalent in patients with idiopathic VTE. The high prevalence of NAFLD in
      VTE was also confirmed after adjustment for inherited thrombophilia. NAFLD was
      clearly predicted by VTE (odds ratio: 1.8, 95% CI: 1.2-2.7, P < 0.0001).
      CONCLUSION: NAFLD was independently associated with idiopathic VTE.

PMID- 21182228
TI  - Extrahepatic portal vein thrombosis in children and adolescents: Influence of
      genetic thrombophilic disorders.
AB  - AIM: to explore the prevalence of local and genetic thrombophilic disorders as
      risk factors for portal vein thrombosis (PVT) in our series, the largest ever
      published in pediatric literature. METHODS: we conducted a case-control study
      enrolling 31 children with PVT and 26 age-matched controls. All were screened for
      thrombophilia, including genetic disorders, protein C, protein S and homocysteine
      deficiencies. All coagulation parameters were studied at least 3 mo after the
      diagnosis of portal vein obstruction. RESULTS: in our study we showed that most
      pediatric patients with PVT have local prothrombotic risk factors, which are
      probably the most important factors leading to PVT. However, there is a clear
      association between the presence of prothrombotic disorders and PVT, suggesting
      that these increase the risk of thrombosis in patients with local factors such as
      perinatal umbilical vein catheterization or sepsis. CONCLUSION: patients with PVT
      should be screened for inherited prothrombotic disorders regardless of a history
      of an obvious local risk factor.

PMID- 21182230
TI  - Role of serotonin in development of esophageal and gastric fundal varices.
AB  - AIM: to determine the effect of free serotonin concentrations in plasma on
      development of esophageal and gastric fundal varices. METHODS: this prospective
      study included 33 patients with liver cirrhosis and 24 healthy controls.
      Ultrasonography and measurement of serotonin concentration in plasma were carried
      out in both groups of subjects. The upper fiber panendoscopy was performed only
      in patients with liver cirrhosis. RESULTS: the mean plasma free serotonin levels
      were much higher in liver cirrhosis patients than in healthy controls (219.0 +/-
      24.2 nmol/L vs 65.4 +/- 18.7 nmol/L, P < 0.0001). There was no significant
      correlation between serotonin concentration in plasma and the size of the
      esophageal varices according to Spearman coefficient of correlation (r(s) = 
      0.217, P > 0.05). However, the correlation of plasma serotonin concentration and
      gastric fundal varices was highly significant (r(s) = -0.601, P < 0.01).
      CONCLUSION: free serotonin is significant in pathogenesis of portal hypertension
      especially in development of fundal varices, indicating the clinical value of
      serotonergic receptor blockers in these patients.

PMID- 21182229
TI  - Tissue factor in predicted severe acute pancreatitis.
AB  - AIM: to study tissue factor (TF) in acute pancreatitis and evaluate the role of
      TF as a predictive marker of severity. METHODS: forty-nine consecutive patients
      admitted to Lund University Hospital, fulfilling the criteria of predicted severe
      acute pancreatitis (AP), were recruited prospectively between 2002 and 2004.
      Blood samples for TF analyses were drawn at inclusion in the study and 12 h, 1 d
      and 3 d later. RESULTS: twenty-seven patients developed mild AP, and 22 patients
      severe AP. At inclusion in the study, the groups were comparable with respect to
      gender, aetiology, Acute Physiology and Chronic Health Evaluation II score, and
      duration of pain. At inclusion in the study and at 12 h, TF was higher in the
      severe AP group (P = 0.035 and P = 0.049, respectively). After 1 and 3 d, no
      differences in TF levels were noted. Interleukin (IL)-6 was significantly higher
      in the severe AP group at all of the studied time points. C-reactive protein
      (CRP) was significantly higher in the AP group at 1 and 3 d. In receiver
      operating characteristic-curves, the area under the curve (AUC) for TF was 0.679
      (P = 0.035) at inclusion in the study, and a cut off level for TF of 40 pg/mL
      showed a sensitivity of 71% and a specificity of 67%, whereas corresponding AUC
      for IL-6 was 0.775, P = 0.001, and for CRP was 0.653. IL-6 showed better AUC
      values than TF at all time points studied. CONCLUSION: TF-levels are raised early
      in severe AP. TF as an early predictive marker of severe AP is superior to CRP,
      but inferior to IL-6.

PMID- 21182231
TI  - Value of duplex Doppler ultrasonography in non-invasive assessment of children
      with chronic liver disease.
AB  - AIM: to investigate the value of duplex Doppler ultrasonography (US) in the
      assessment of the hemodynamics of the portal and hepatic veins in a cohort of
      children with chronic liver disease (CLD) and to detect any relationship between
      the US changes, etiology and severity (or stage) of CLD. METHODS: we
      prospectively enrolled 25 children with biopsy-proven CLD. Thirteen had cirrhosis
      (aged 8.9 +/- 2.0 years) and 12 had chronic hepatitis (aged 9.3 +/- 2.3 years).
      Gray scale and color-coded duplex Doppler US were performed for all, as well as
      30 healthy age and sex-matched controls. Findings were correlated with clinical,
      laboratory and histopathological characteristics. RESULTS: prominent caudate lobe
      was detected in 100% of cirrhotics, but none of the chronic hepatitis or
      controls. Thickened lesser omentum and loss of the triphasic waveform of the
      hepatic vein were present in 69.2% and 53.8% of cirrhotics vs 33.3% and 8.3% of
      chronic hepatitis respectively. Portal vein flow velocity was significantly lower
      (P < 0.0001) and the congestion index was significantly higher (P < 0.005) in
      both patient groups compared to controls. Child-Pugh's staging showed a positive
      correlation with both abnormal hepatic vein waveform and direction of portal
      blood flow; and a negative correlation with both hepatic and portal vein flow
      velocities. No correlation with the etiology of CLD could be detected.
      CONCLUSION: duplex Doppler added to grayscale US can detect significant
      morphologic and portal hemodynamic changes that correlate with the severity
      (stage) of CLD, but not with etiology.

PMID- 21182232
TI  - Pegylated interferon alpha-2b up-regulates specific CD8+ T cells in patients with
      chronic hepatitis B.
AB  - AIM: to investigate the effect of pegylated interferon (IFN) alpha-2b on specific
      CD8+ T lymphocytes in patients with chronic hepatitis B (CHB). METHODS: twenty
      one patients with CHB were treated with pegylated IFN alpha-2b. Periphery blood
      mononuclear cells were isolated from fresh heparinized blood by Ficoll-Hypaque
      density gradient centrifugation (density: 1.077 g/L, Pharmingen) at weeks 0, 4,
      8, 12, and 24, respectively. Frequency of circulating hepatitis B virus (HBV)
      epitope-specific CD8 T cells was detected by flow cytometry. Cytokines were
      detected by cytometric bead assay. RESULTS: the frequency of circulating HBV core
      or env-specific CD8 T cells was higher (P < 0.05), the number of HBV core
      specific CD8 T cells was greater at week 24 (P < 0.05), the level of Th1-type
      cytokines [interleukin (IL)-12, tumor necrosis factor-alpha, and IFN-gamma] was
      higher, while that of Th2-type cytokines (IL-4, IL-6, and IL-10) was lower in
      responders than in non-responders (P < 0.05) after pegylated IFN alpha-2b
      treatment. The IL-6 level was correlated with HBV DNA (r = 0.597, P = 0.04),
      while the inducible protein-10 (IP-10) level was correlated with serum alanine
      aminotransferase (ALT) (r = 0.545, P = 0.005). The IP-10 level at week 8 after
      pegylated IFN alpha-2b treatment could predict the normalization of ALT in CHB
      patients (positive predict value = 56%, negative predict value = 92%).
      CONCLUSION: pegylated IFN alpha-2b can enhance the immune response of CHB
      patients by increasing the frequency of HBV specific CD8+ T cells and regulating
      the Th1/Th2 cytokines.

PMID- 21182233
TI  - Short-segment Barrett's esophagus and cardia intestinal metaplasia: A comparative
      analysis.
AB  - AIM: to investigate the endoscopy and histology of short-segment Barrett's
      esophagus (SSBE) and cardia intestinal metaplasia (CIM), and their correlation
      with Helicobacter pylori (H. pylori) gastritis and gastroesophageal reflux
      disease (GERD). METHODS: biopsy specimens were taken from 32 SSBE patients and 41
      CIM patients with normal appearance of the esophagogastric junction. Eight biopsy
      specimens from the lower esophagus, cardia, and gastric antrum were stained with
      hematoxylin/eosin, Alcian blue/periodic acid-Schiff, Alcian blue/high iron
      diamine and Gimenez dye. Results were graded independently by one pathologist.
      RESULTS: the SSBE patients were younger than the CIM patients (P < 0.01). The
      incidence of dysplasia and incomplete intestinal metaplasia subtype was higher in
      SSBE patients than in CIM patients (P < 0.01). H. pylori infection was correlated
      with antral intestinal metaplasia (P < 0.05), but not with reflux symptomatic,
      endoscopic, or histological markers of GERD in CIM patients. SSBE was correlated
      with reflux symptomatic and endoscopic esophagitis (P < 0.01), but not with H.
      pylori infection and antral intestinal metaplasia. CONCLUSION: dysplasia risk is
      significantly greater in SSBE patients than in CIM patients. CIM is a
      manifestation of H. pylori-associated and multifocal atrophic gastritis, whereas
      SSBE may result from GERD.

PMID- 21182235
TI  - Co-electrospun blends of PLGA, gelatin, and elastin as potential nonthrombogenic
      scaffolds for vascular tissue engineering.
AB  - In search for novel biomimetic scaffolds for application in vascular tissue
      engineering, we evaluated a series of fibrous scaffolds prepared by
      coelectrospinning tertiary blends of poly(lactide-co-glycolide) (PLGA), gelatin,
      and elastin (PGE). By systematically varying the ratios of PLGA and gelatin, we
      could fine-tune fiber size and swelling upon hydration as well as the mechanical
      properties of the scaffolds. Of all PGE blends tested, PGE321 (PLGA, gelatin,
      elastin v/v/v ratios of 3:2:1) produced the smallest fiber size (317 +/- 46 nm,
      446 +/- 69 nm once hydrated) and exhibited the highest Young's modulus (770 +/-
      131 kPa) and tensile strength (130 +/- 7 kPa). All PGE scaffolds supported the
      attachment and metabolization of human endothelial cells (ECs) and bovine aortic
      smooth muscle cells (SMCs) with some variances in EC morphology and cytoskeletal
      spreading observed at 48 h postseeding, whereas no morphologic differences were
      observed at confluence (day 8). The rate of metabolization of ECs, but not of
      SMCs, was lower than that on tissue culture plastic and depended on the specific
      PGE composition. Importantly, PGE scaffolds were capable of guiding the
      organotypic distribution of ECs and SMCs on and within the scaffolds,
      respectively. Moreover, the EC monolayer generated on the PGE scaffold surface
      was nonthrombogenic and functional, as assessed by the basal and cytokine
      inducible levels of mRNA expression and amidolytic activity of tissue factor, a
      key player in the extrinsic clotting cascade. Taken together, our data indicate
      the potential application of PGE scaffolds in vascular tissue engineering.

PMID- 21182236
TI  - Engineered cartilage covered ear implants for auricular cartilage reconstruction.
AB  - Cartilage tissues are often required for auricular tissue reconstruction.
      Currently, alloplastic ear-shaped medical implants composed of silicon and
      polyethylene are being used clinically. However, the use of these implants is
      often associated with complications, including inflammation, infection, erosion,
      and dislodgement. To overcome these limitations, we propose a system in which
      tissue-engineered cartilage serves as a shell that entirely covers the
      alloplastic implants. This study investigated whether cartilage tissue,
      engineered with chondrocytes and a fibrin hydrogel, would provide adequate
      coverage of a commercially used medical implant. To demonstrate the in vivo
      stability of cell-fibrin constructs, we tested variations of fibrinogen and
      thrombin concentration as well as cell density. After implantation, the retrieved
      engineered cartilage tissue was evaluated by histo- and immunohistochemical,
      biochemical, and mechanical analyses. Histomorphological evaluations consistently
      showed cartilage formation over the medical implants with the maintenance of
      dimensional stability. An initial cell density was determined that is critical
      for the production of matrix components such as glycosaminoglycans (GAG),
      elastin, type II collagen, and for mechanical strength. This study shows that
      engineered cartilage tissues are able to serve as a shell that entirely covers
      the medical implant, which may minimize the morbidity associated with implant
      dislodgement.

PMID- 21182237
TI  - Effects of peptide secondary structure on the interaction with oppositely charged
      microgels.
AB  - The importance of peptide secondary structure on the interaction between
      antimicrobial peptides and oppositely charged poly(acrylic acid-co-acrylamide)
      microgels of various charge density was investigated for EFKRIVQRIKDFLRNLV
      (EFK17). Through D-enantiomer (EFK17-d/a; E(dF)KR(dI)VQR(dI)KD(dF)LRNLV) or
      tryptophan (EFK17-W/a; EWKRWVQRWKDFLRNLV) substitutions, both conformation
      dependent and -independent amphiphilicity of this peptide could be precisely
      controlled. Peptide secondary structure was investigated by circular dichroism,
      whereas microgel deswelling and reswelling in response to peptide binding and
      release were studied by micromanipulator-assisted light and fluorescence
      microscopy, and peptide uptake in the microgels was determined from solution
      depletion measurements. Results show that peptide binding to the microgel is
      highly influenced by peptide secondary structure. EFK17-a, characterized by an
      idealized helix with all polar/charged amino acids located at one side of the
      helix, and all nonpolar/hydrophobic residues on the other, displays pronounced
      alpha-helix induction on peptide binding to the microgels. EFK17-d/a, on the
      other hand, displays no such amphiphilic helix induction. Mirroring this, EFK17-a
      displays substantially higher binding to the microgels than EFK17-d/a as well as
      much larger peptide-induced microgel deswelling. For EFK17-W/a, both conformation
      dependent and -independent amphiphilicity effects were demonstrated. Overall, the
      results show that peptide conformational aspects need to be considered in
      peptide/microgel interactions, for example, in the design of microgel carrier
      systems for peptide drugs.

PMID- 21182234
TI  - Increasing the frequency of CIK cells adoptive immunotherapy may decrease risk of
      death in gastric cancer patients.
AB  - AIM: to analyze the correlation between cytokine-induced killer (cik) cells
      adoptive immunotherapy and cancer-related death in gastric cancer patients.
      methods: One hundred and fifty-six gastric cancer patients after operation at the
      Third Affiliated Hospital of Soochow University were enrolled in this study.
      Their clinical data including demographic characteristics, operation time, tumor
      size, pathological type and staging, tumor metastasis, outcome of chemotherapy or
      CIK cells adoptive immunotherapy, survival time or time of death were collected
      with a standard structured questionnaire. Kaplan-Meier method was used to
      estimate the median survival time, and the 2- and 5- year survival rates. Hazard
      risk (HR) and 95% confidence interval (95% CI) of CIK cells adoptive
      immunotherapy for gastric cancer were calculated using the two-stage time
      dependent covariates Cox model. RESULTS: the survival time of gastric cancer
      patients was longer after CIK cells adoptive immunotherapy than after
      chemotherapy (chi(2) = 10.907, P = 0.001). The median survival time of gastric
      cancer patients was also longer after CIK cells adoptive immunotherapy than after
      chemotherapy (49 mo vs 27 mo, P < 0.05). The 2- and 5-year survival rates of
      gastric cancer patients were significantly higher after CIK cells adoptive
      immunotherapy than after chemotherapy (73.5% vs 52.6%, 40.4% vs 23.9%, P < 0.05).
      A significant difference was observed in the survival curve for patients who
      received CIK cells adoptive immunotherapy (0, 1-10, 11-25, and over 25
      frequencies) (chi(2) = 14.534, P = 0.002). The frequencies of CIK cells adoptive
      immunotherapy were significantly related with the decreasing risk of death in
      gastric cancer patients after adjustment for sex and age of the patients, tumor
      stage and relapse (HR = 0.54, 95% CI: 0.36-0.80) when the first stage Cox model
      was used to define the subjects who remained alive beyond 36 mo as survivors.
      However, no correlation was observed between the frequencies of death in CIK
      cells adoptive immunotherapy and the risk of gastric cancer patients (HR = 1.09,
      95% CI: 0.63-0.89) when the second stage Cox model was used to define the
      subjects who survived for more than 36 mo as survivors. CONCLUSION: the survival
      time of the gastric cancer patients treated with chemotherapy combined with CIK
      cells adoptive immunotherapy is significantly longer than that of the patients
      treated with chemotherapy alone and increasing the frequency of CIK cells
      adoptive immunotherapy seems to benefit patients more.

PMID- 21182238
TI  - Friction force spectroscopy of beta- and kappa-casein monolayers.
AB  - Friction force spectroscopy (FFS) has been applied to study the tribological
      properties of beta- and kappa-casein layers on hydrophobic substrates in aqueous
      solutions. Nanometer-sized imaging tips were employed. This allowed exerting and
      determining the high pressures needed to remove the layers and registering the
      topographic evolution during this process. Both beta- and kappa-casein layers
      showed similar and not particularly high initial frictional responses (friction
      coefficient of ~1 when measured with a silicon nitride tip). The pressures needed
      to remove the layers were of the same order of magnitude for both proteins,
      ~10(8) Pa, but slightly higher for those composed of beta-casein. The technique
      has also shown to be useful in studying the two-dimensional lateral diffusion of
      the proteins and the wear on the layers they form.

PMID- 21182239
TI  - Ultrasound-triggered smart drug release from multifunctional core-shell capsules
      one-step fabricated by coaxial electrospray method.
AB  - Multifunctional core-shell capsules that triggered release by ultrasound stimulus
      were one-step fabricated by the coaxial electrospray method. The TiO(2) shell
      suppressed the initial burst release of the paclitaxel. Fe(3)O(4) and graphene
      quantum dots inside the oil core functioned successfully for magnetic targeting
      and fluorescence imaging, respectively. Paclitaxel was trigger released when the
      dual layer of titania shell cracked under the ultrasound stimulation, and the
      releasing profile could be controlled by the length of applied ultrasound time.

PMID- 21182240
TI  - Consistency between kinetics and thermodynamics: general scaling conditions for
      reaction rates of nonlinear chemical systems without constraints far from
      equilibrium.
AB  - We examine the problem of consistency between the kinetic and thermodynamic
      descriptions of reaction networks. We focus on reaction networks with linearly
      dependent (but generally kinetically independent) reactions for which only some
      of the stoichiometric vectors attached to the different reactions are linearly
      independent. We show that for elementary reactions without constraints preventing
      the system from approaching equilibrium there are general scaling relations for
      nonequilibrium rates, one for each linearly dependent reaction. These scaling
      relations express the ratios of the forward and backward rates of the linearly
      dependent reactions in terms of products of the ratios of the forward and
      backward rates of the linearly independent reactions raised to different scaling
      powers; the scaling powers are elements of the transformation matrix, which
      relates the linearly dependent stoichiometric vectors to the linearly independent
      stoichiometric vectors. These relations are valid for any network of elementary
      reactions without constraints, linear or nonlinear kinetics, far from equilibrium
      or close to equilibrium. We show that similar scaling relations for the reaction
      routes exist for networks of nonelementary reactions described by the Horiuti
      Temkin theory of reaction routes where the linear dependence of the mechanistic
      (elementary) reactions is transferred to the overall (route) reactions. However,
      in this case, the scaling conditions are valid only at the steady state. General
      relationships between reaction rates of the two levels of description are
      presented. These relationships are illustrated for a specific complex reaction:
      radical chlorination of ethylene.

PMID- 21182241
TI  - Nonperturbative chemical modification of graphene for protein micropatterning.
AB  - Graphene's extraordinary physical properties and its planar geometry make it an
      ideal candidate for a wide array of applications, many of which require
      controlled chemical modification and the spatial organization of molecules on its
      surface. In particular, the ability to functionalize and micropattern graphene
      with proteins is relevant to bioscience applications such as biomolecular
      sensors, single-cell sensors, and tissue engineering. We report a general
      strategy for the noncovalent chemical modification of epitaxial graphene for
      protein immobilization and micropatterning. We show that bifunctional molecule
      pyrenebutanoic acid-succinimidyl ester (PYR-NHS), composed of the hydrophobic
      pyrene and the reactive succinimide ester group, binds to graphene noncovalently
      but irreversibly. We investigate whether the chemical treatment perturbs the
      electronic band structure of graphene using X-ray photoemission (XPS) and Raman
      spectroscopy. Our results show that the sp(2) hybridization remains intact and
      that the pi band maintains its characteristic Lorentzian shape in the Raman
      spectra. The modified graphene surfaces, which bind specifically to amines in
      proteins, are micropatterned with arrays of fluorescently labeled proteins that
      are relevant to glucose sensors (glucose oxidase) and cell sensor and tissue
      engineering applications (laminin).

PMID- 21182242
TI  - Protein-associated water and secondary structure effect removal of blood proteins
      from metallic substrates.
AB  - Removing adsorbed protein from metals has significant health and industrial
      consequences. There are numerous protein-adsorption studies using model self
      assembled monolayers or polymeric substrates but hardly any high-resolution
      measurements of adsorption and removal of proteins on industrially relevant
      transition metals. Surgeons and ship owners desire clean metal surfaces to reduce
      transmission of disease via surgical instruments and minimize surface fouling (to
      reduce friction and corrosion), respectively. A major finding of this work is
      that, besides hydrophobic interaction adhesion energy, water content in an
      adsorbed protein layer and secondary structure of proteins determined the access
      and hence ability to remove adsorbed proteins from metal surfaces with a strong
      alkaline-surfactant solution (NaOH and 5 mg/mL SDS in PBS at pH 11). This is
      demonstrated with three blood proteins (bovine serum albumin, immunoglobulin, and
      fibrinogen) and four transition metal substrates and stainless steel (platinum
      (Pt), gold (Au), tungsten (W), titanium (Ti), and 316 grade stainless steel
      (SS)). All the metallic substrates were checked for chemical contaminations like
      carbon and sulfur and were characterized using X-ray photoelectron spectroscopy
      (XPS). While Pt and Au surfaces were oxide-free (fairly inert elements), W, Ti,
      and SS substrates were associated with native oxide. Difference measurements
      between a quartz crystal microbalance with dissipation (QCM-D) and surface
      plasmon resonance spectroscopy (SPR) provided a measure of the water content in
      the protein-adsorbed layers. Hydrophobic adhesion forces, obtained with atomic
      force microscopy, between the proteins and the metals correlated with the amount
      of the adsorbed protein-water complex. Thus, the amount of protein adsorbed
      decreased with Pt, Au, W, Ti and SS, in this order. Neither sessile contact angle
      nor surface roughness of the metal substrates was useful as predictors here. All
      three globular proteins behaved similarly on addition of the alkaline-surfactant
      cleaning solution, in that platinum and gold exhibited an increase, while
      tungsten, titanium, and stainless steel showed a decrease in weight. According to
      dissipation measurements with the QCM-D, the adsorbed layer for platinum and gold
      was rigid, while that for the tungsten, titanium, and stainless steel was much
      more flexible. The removal efficiency of adsorbed-protein by alkaline solution of
      SDS depended on the water content of the adsorbed layers for W, Ti, and SS, while
      for Pt and Au, it depended on secondary structural content. When protein
      adsorption was high (Pt, Au), protein-protein interactions and protein-surface
      interactions were dominant and the removal of protein layers was limited. Water
      content of the adsorbed protein layer was the determining factor for how
      efficiently the layer was removed by alkaline SDS when protein adsorption was
      low. Hence, protein-protein and protein-surface interactions were minimal and
      protein structure was less perturbed in comparison with those for high protein
      adsorption. Secondary structural content determined the efficient removal of
      adsorbed protein for high adsorbed amount.

PMID- 21182243
TI  - Computing fragmentation trees from tandem mass spectrometry data.
AB  - The structural elucidation of organic compounds in complex biofluids and tissues
      remains a significant analytical challenge. For mass spectrometry, the manual
      interpretation of collision-induced dissociation (CID) mass spectra is cumbersome
      and requires expert knowledge, as the fragmentation mechanisms of ions formed
      from small molecules are not completely understood. The automated identification
      of compounds is generally limited to searching in spectral libraries. Here, we
      present a method for interpreting the CID spectra of the organic compound's
      protonated ions by computing fragmentation trees that establish not only the
      molecular formula of the compound and all fragment ions but also the dependencies
      between fragment ions. This is an important step toward the automated
      identification of unknowns from the CID spectra of compounds that are not in any
      database.

PMID- 21182244
TI  - In situ tracking of enzymatic breakdown of starch granules by synchrotron UV
      fluorescence microscopy.
AB  - Synchrotron UV fluorescence microscopy was used for the first time to visualize
      the adsorption and diffusion of an enzyme while degrading a solid substrate. The
      degradation pathway of single starch granules by two amylases, optimized for
      biofuel production and industrial starch hydrolysis, was followed by tryptophan
      fluorescence (excitation at 280 nm, emission filter at 300-400 nm) and visible
      light imaging. Thus, both the adsorption of enzyme onto starch granules at 283 nm
      resolution and the resulting morphological changes were recorded at different
      stages of hydrolysis. It is the first time that amylases were localized on starch
      without staining or adding a fluorescent probe at such high resolution. This
      technique presents a very high potential for imaging proteins in complex systems.
      Its sensitivity was demonstrated by the detection of GBSS (the granular bound
      starch synthase) at high recording times, GBSS being present at very low levels
      in maize starch granules.

PMID- 21182245
TI  - In-situ loading ultrafine AuPd particles on ceria: highly active catalyst for
      solvent-free selective oxidation of benzyl alcohol.
AB  - Ce(III) oxide was synthesized under the protection of nitrogen gas, which had
      strong ability to reduce noble metal ions (e.g., Au, Pd ions) into metallic forms
      under oxygen-free conditions. On the basis of the surface redox reaction between
      the Ce(III) oxide support and noble metal ions, an effective and novel approach
      was presented to prepare noble metal/CeO(2) nanocatalysts, and a series of
      AuPd/CeO(2) nanocomposites with different Au:Pd molar ratios and metal loadings
      were obtained in the absence of any extra reducing and protective agents. The
      resultant composites were characterized by different techniques including X-ray
      diffraction, transmission electron microspectroscopy, X-ray photoelectron
      microspectroscopy, and ICP-AES analysis. It was demonstrated that in the
      AuPd/CeO(2) composites the content of Ce(III) reached about 30%, and the AuPd
      bimetallic particles with average size of 2.6 or 3.3 nm and narrow size
      distribution were uniformly distributed on the CeO(2) nanorods. The AuPd/CeO(2)
      composites were found to be excellent heterogeneous nanocatalysts for the
      selective oxidation of benzyl alcohol under solvent-free conditions. It was shown
      that all the AuPd/CeO(2) catalysts exhibited good selectivity toward
      benzaldehyde; especially, the catalyst with Au:Pd = 1:5 and metal loading of 1.2
      wt % displayed extremely high activity with a TOF = 30.1 s(-1) at 160  degrees C.

PMID- 21182246
TI  - Nanofilm biomaterials: localized cross-linking to optimize mechanical rigidity
      and bioactivity.
AB  - Nanofilm biomaterials, formed by the layer-by-layer assembly of charged
      macromolecules, are important systems for a variety of cell-contacting biomedical
      and biotechnological applications. Mechanical rigidity and bioactivity are two
      key film properties influencing the behavior of contacting cells. Increased
      rigidity tends to improve cells attachment, and films may be rendered bioactive
      through the incorporation of proteins, peptides, or drugs. A key challenge is to
      realize films that are simultaneously rigid and bioactive. Chemical cross-linking
      of the polymer framework--the standard means of increasing a film's rigidity--can
      diminish bioactivity through deactivation or isolation of embedded biomolecules
      or inhibition of film biodegradation. We present here a strategy to decouple
      mechanical rigidity and bioactivity, potentially enabling nanofilm biomaterials
      that are both mechanically rigid and bioactive. Our idea is to selectively cross
      link the outer region of the film, resulting in a rigid outer skin to promote
      cell attachment, while leaving the film interior (with any embedded bioactive
      species) unaffected. We propose an approach whereby an N-hydroxysulfosuccinimide
      (sulfo-NHS) activated poly(L-glutamic acid) is added as the terminal layer of a
      multilayer film and forms (covalent) amide bonds with amino groups of poly(L
      lysine) placed previously within the film. We characterize film assembly and
      cross-linking extent via quartz crystal microbalance with dissipation monitoring
      (QCMD), Fourier transform infrared spectroscopy in attenuated total reflection
      mode (FTIR-ATR), and laser scanning confocal microscopy (LSCM) and measure the
      attachment and metabolic activity of preosteoblastic MC3T3-E1 cells. We show
      cross-linking to occur primarily at the film surface and the subsequent cell
      attachment and metabolic activity to be enhanced compared to native films. Our
      method appears promising as a means to realize films that are simultaneously
      mechanically rigid and bioactive.

PMID- 21182247
TI  - Rearrangement of the tris(2-pyridylthio)methanido ligand in an iron(II) complex
      containing an Fe-C bond.
AB  - Iron(II) tris(2-pyridylthio)methanido (1) containing an Fe-C bond, obtained from
      the reaction of tris(2-pyridylthio)methane (HL(1)) and iron(II) triflate, reacts
      with protic acid to generate iron(II) bis(2-pyridylthio)carbene (1a). The carbene
      complex is converted to an iron(II) complex (2) of the 1-[bis(2
      pyridylthio)methyl]pyridine-2-thione ligand (L(3)) upon treatment with a base.
      Complex 2 reversibly transforms to 1a in the presence of an acid. During the
      transformation of 1 to 2, a novel rearrangement of L(1) to L(3) takes place. The
      iron(II) complexes are reactive toward dioxygen to form the corresponding
      iron(III) complexes.

PMID- 21182248
TI  - Quantum dots with phenylboronic acid tags for specific labeling of sialic acids
      on living cells.
AB  - Sialic acids with a nine-carbon backbone are commonly found at the terminal
      position of the glycans structures on cell membranes. The unique distribution and
      ubiquitous existence of sialic acid on the cell membrane make them important
      mediators in various biological and pathological processes. We report a new class
      of imaging probes based on semiconductor quantum dots with small molecular
      phenylboronic acid tags for highly specific and efficient labeling of sialic acid
      on living cells. Our results have shown that the use of these probes enables one
      step labeling and continuous tracking of the cell surface sialic acid moieties
      without any pretreatment of living cells. The one-step procedure with fast
      binding kinetics and the biocompatibility of these probes make it an ideal
      noninvasive technology for living cell imaging. We also find that the labeled
      sialic acids undergo quick internalization shortly after surface binding via
      endocytosis and eventually distribute in the perinuclear region. This
      distribution pattern is consistent with the notion that sialylated glycoproteins
      are populated on cell membranes and recycled through the vesicular exocytotic and
      endocytic pathways. The superior photostability and brightness of quantum dots
      enable quantitative analysis of the diffusion dynamics of sialic acids, which has
      been a significant challenge for glycan imaging.

PMID- 21182250
TI  - SiC2 silagraphene and its one-dimensional derivatives: where planar
      tetracoordinate silicon happens.
AB  - The periodic systems containing planar tetracoordinate silicon (ptSi), SiC(2)
      silagraphene, nanotubes, and nanoribbons, were predicted by means of density
      functional theory (DFT) computations. In SiC(2) silagraphene, each silicon atom
      is bonded by four carbon atoms in a pure plane, representing the first anti-van't
      Hoff/Lebel species in the Si-containing extended system. SiC(2) nanotubes, rolled
      up by the SiC(2) silagraphene, exhibit excellent elastic properties. All these
      ptSi-containing nanomaterials are metallic, regardless of the chirality, tube
      diameter, or ribbon width. The high stabilities of these systems strongly suggest
      the feasibility for their experimental realizations.

PMID- 21182249
TI  - Mechanistic insight into the nitrosylation of the [4Fe-4S] cluster of WhiB-like
      proteins.
AB  - The reactivity of protein bound iron-sulfur clusters with nitric oxide (NO) is
      well documented, but little is known about the actual mechanism of cluster
      nitrosylation. Here, we report studies of members of the Wbl family of [4Fe-4S]
      containing proteins, which play key roles in regulating developmental processes
      in actinomycetes, including Streptomyces and Mycobacteria, and have been shown to
      be NO responsive. Streptomyces coelicolor WhiD and Mycobacterium tuberculosis
      WhiB1 react extremely rapidly with NO in a multiphasic reaction involving,
      remarkably, 8 NO molecules per [4Fe-4S] cluster. The reaction is 10(4)-fold
      faster than that observed with O(2) and is by far the most rapid iron-sulfur
      cluster nitrosylation reaction reported to date. An overall stoichiometry of
      [Fe(4)S(4)(Cys)(4)](2-) + 8NO -> 2[Fe(I)(2)(NO)(4)(Cys)(2)](0) + S(2-) + 3S(0)
      has been established by determination of the sulfur products and their oxidation
      states. Kinetic analysis leads to a four-step mechanism that accounts for the
      observed NO dependence. DFT calculations suggest the possibility that the
      nitrosylation product is a novel cluster [Fe(I)(4)(NO)(8)(Cys)(4)](0) derived by
      dimerization of a pair of Roussin's red ester (RRE) complexes.

PMID- 21182251
TI  - Rectangular patterns using block copolymer directed assembly for high bit aspect
      ratio patterned media.
AB  - We report a nanofabrication method that combines block copolymer directed
      assembly with e-beam lithography to achieve highly uniform rectangular patterns
      with a critical dimension of 16 nm, a full pitch of 27 nm, and arbitrary aspect
      ratio. This fabrication method enables geometries that are not natural to block
      copolymer assembly, preserves both the feature uniformity and the center-to
      center spacing of the original block copolymer, sustains long-range translational
      order, and facilitates high-resolution, high-density patterns through feature
      density multiplication. These highly uniform arrays of dense rectangular features
      are particularly attractive for fabricating magnetic bit patterned media with
      high bit aspect ratio.

PMID- 21182252
TI  - Wavefront velocity oscillations of carbon-nanotube-guided thermopower waves:
      nanoscale alternating current sources.
AB  - The nonlinear coupling between exothermic chemical reactions and a nanowire or
      nanotube with large axial heat conduction results in a self-propagating thermal
      wave guided along the nanoconduit. The resulting reaction wave induces a
      concomitant thermopower wave of high power density (>7 kW/kg), resulting in an
      electrical current along the same direction. We develop the theory of such waves
      and analyze them experimentally, showing that for certain values of the chemical
      reaction kinetics and thermal parameters, oscillating wavefront velocities are
      possible. We demonstrate such oscillations experimentally using a
      cyclotrimethylene-trinitramine/multiwalled carbon nanotube system, which produces
      frequencies in the range of 400 to 5000 Hz. The propagation velocity oscillations
      and the frequency dispersion are well-described by Fourier's law with an
      Arrhenius source term accounting for reaction and a linear heat exchange with the
      nanotube scaffold. The frequencies are in agreement with oscillations in the
      voltage generated by the reaction. These thermopower oscillations may enable new
      types of nanoscale power and signal processing sources.

PMID- 21182253
TI  - First principle kinetic studies of zeolite-catalyzed methylation reactions.
AB  - Methylations of ethene, propene, and butene by methanol over the acidic
      microporous H-ZSM-5 catalyst are studied by means of state of the art
      computational techniques, to derive Arrhenius plots and rate constants from first
      principles that can directly be compared with the experimental data. For these
      key elementary reactions in the methanol to hydrocarbons (MTH) process, direct
      kinetic data became available only recently [J. Catal.2005, 224, 115-123; J.
      Catal.2005, 234, 385-400]. At 350  degrees C, apparent activation energies of
      103, 69, and 45 kJ/mol and rate constants of 2.6 * 10(-4), 4.5 * 10(-3), and 1.3
      * 10(-2) mol/(g h mbar) for ethene, propene, and butene were derived, giving
      following relative ratios for methylation k(ethene)/k(propene)/k(butene) =
      1:17:50. In this work, rate constants including pre-exponential factors are
      calculated which give very good agreement with the experimental data: apparent
      activation energies of 94, 62, and 37 kJ/mol for ethene, propene, and butene are
      found, and relative ratios of methylation k(ethene)/k(propene)/k(butene) =
      1:23:763. The entropies of gas phase alkenes are underestimated in the harmonic
      oscillator approximation due to the occurrence of internal rotations. These low
      vibrational modes were substituted by manually constructed partition functions.
      Overall, the absolute reaction rates can be calculated with near chemical
      accuracy, and qualitative trends are very well reproduced. In addition, the
      proposed scheme is computationally very efficient and constitutes significant
      progress in kinetic modeling of reactions in heterogeneous catalysis.

PMID- 21182255
TI  - Graphene growth on Ni(111) by transformation of a surface carbide.
AB  - A novel growth mechanism of graphene on Ni(111) has been discovered that occurs
      at temperatures below 460  degrees C. At these conditions, a surface-confined
      nickel-carbide phase coexists with single layer graphene. The graphene grows by
      in-plane transformation of the carbide along a one-dimensional phase-boundary,
      which is distinctively different from known growth processes on other transition
      metals and on Ni above 460  degrees C, where carbon atoms attach to "free" edges
      of graphene islands.

PMID- 21182254
TI  - Universal peptidomimetics.
AB  - This paper concerns peptidomimetic scaffolds that can present side chains in
      conformations resembling those of amino acids in secondary structures without
      incurring excessive entropic or enthalpic penalties. Compounds of this type are
      referred to here as minimalist mimics. The core hypothesis of this paper is that
      small sets of such scaffolds can be designed to analogue local pairs of amino
      acids (including noncontiguous ones) in any secondary structure; i.e., they are
      universal peptidomimetics. To illustrate this concept, we designed a set of four
      peptidomimetic scaffolds. Libraries based on them were made bearing side chains
      corresponding to many of the protein-derived amino acids. Modeling experiments
      were performed to give an indication of kinetic and thermodynamic accessibilities
      of conformations that can mimic secondary structures. Together, peptidomimetics
      based on these four scaffolds can adopt conformations that resemble almost any
      combination of local amino acid side chains in any secondary structure. Universal
      peptidomimetics of this kind are likely to be most useful in the design of
      libraries for high-throughput screening against diverse targets. Consequently,
      data arising from submission of these molecules to the NIH Molecular Libraries
      Small Molecule Repository (MLSMR) are outlined.

PMID- 21182256
TI  - White-light-emitting self-assembled nanofibers and their evidence by
      microspectroscopy of individual objects.
AB  - The self-assembly of a blue-emitting light-harvesting organogelator and
      specifically designed highly fluorescent tetracenes yields nanofibers with
      tunable emissive properties. In particular, under near-UV excitation, white light
      emission is achieved in organogels and dry films of nanofibers. Confocal
      fluorescence microspectroscopy demonstrates that each individual nanofiber emits
      white light. A kinetic study shows that an energy transfer (ET) occurs between
      the blue-emitting anthracene derivative and the green- and red-emitting
      tetracenes, while inter-tetracene ETs also take place. Moreover, microscopy
      unravels that the nanofibers emit polarized emission in the blue spectral region,
      while at wavelengths higher than 500 nm the emission is not significantly
      polarized.

PMID- 21182257
TI  - X-ray excited optical luminescence from hexagonal boron nitride nanotubes:
      electronic structures and the role of oxygen impurities.
AB  - We report a study on the optical luminescence properties and the electronic
      structures of boron nitride nanotubes (BNNTs). BNNTs with natural B (80% (11)B
      and 20% (10)B) and pure (10)B are investigated in comparison with hexagonal BN
      crystals using X-ray absorption near-edge structures (XANES) and X-ray excited
      optical luminescence (XEOL). We find that the BNNT specimen synthesized with
      natural B contains more oxide impurities than that with pure (10)B, resulting in
      significantly different behavior in optical luminescence. All BN samples with
      hexagonal structures are found to emit strong luminescence, but the emission
      spectra are strongly morphology- and structure-dependent. XEOL and XANES
      measurements were carried out at the B K-edge, N K-edge, and O K-edge in order to
      reveal the origin of different luminescence channels and the corresponding
      electronic structures in these BN materials.

PMID- 21182258
TI  - Tirucallane triterpenoids from Cornus walteri.
AB  - Twelve new tirucallane triterpenoids, named cornusalterins A-L (1-12), and two
      known tirucallane triterpenoids, deoxyflindissone (13) and (-)-leucophyllone
      (14), were isolated from a MeOH extract of stems and stem bark of Cornus walteri.
      The structures of the new compounds were determined by spectroscopic methods,
      including 1D and 2D NMR analyses. Compounds 12 and 13, possessing a
      tetrahydrofuran ring in the side chain, exhibited significant cytotoxic activity
      against the A549, SK-OV-3, SK-MEL-2, and XF498 cell lines.

PMID- 21182260
TI  - One-pot construction of aza- or oxa-bridged benzocycloheptanes from readily
      available 2,3-allenyl malonates or 2,3-allenols and o-iodobenzaldehyde or imine.
AB  - A Pd(OAc)(2)-catalyzed reaction of 2,3-alkadienyl malonates or 2,3-allenols with
      o-iodobenzaldehyde or its N-tosyl imine occurred smoothly in MeCN at 80  degrees
      C to form the oxa- or aza-bridged benzocycloheptane derivatives with important
      biological potential. With the optically active 2,3-allenols, the absolute
      configurations of all the three chiral centers have been conveniently
      established.

PMID- 21182259
TI  - Reconstituted lipoprotein: a versatile class of biologically-inspired
      nanostructures.
AB  - One of biology's most pervasive nanostructures, the phospholipid membrane,
      represents an ideal scaffold for a host of nanotechnology applications. Whether
      engineering biomimetic technologies or designing therapies to interface with the
      cell, this adaptable membrane can provide the necessary molecular-level control
      of membrane-anchored proteins, glycopeptides, and glycolipids. If appropriately
      prepared, these components can replicate in vitro or influence in vivo essential
      living processes such as signal transduction, mass transport, and chemical or
      energy conversion. To satisfy these requirements, a lipid-based, synthetic
      nanoscale architecture with molecular-level tunability is needed. In this regard,
      discrete lipid particles, including reconstituted high density lipoprotein (HDL),
      have emerged as a versatile and elegant solution. Structurally diverse, native
      biological HDLs exist as discoidal lipid bilayers of 5-8 nm diameter and lipid
      monolayer-coated spheres 10-15 nm in diameter, all belted by a robust scaffolding
      protein. These supramolecular assemblies can be reconstituted using simple self
      assembly methods to incorporate a broad range of amphipathic molecular
      constituents, natural or artificial, and provide a generic platform for
      stabilization and transport of amphipathic and hydrophobic elements capable of
      docking with targets at biological or inorganic surfaces. In conjunction with top
      down or bottom-up engineering approaches, synthetic HDL can be designed, arrayed,
      and manipulated for a host of applications including biochemical analyses and
      fundamental studies of molecular structure. Also highly biocompatible, these
      assemblies are suitable for medical diagnostics and therapeutics. The collection
      of efforts reviewed here focuses on laboratory methods by which synthetic HDLs
      are produced, the advantages conferred by their nanoscopic dimension, and current
      and emerging applications.

PMID- 21182261
TI  - Thermodynamics and structural features of the yeast Saccharomyces cerevisiae
      external invertase isoforms in guanidinium-chloride solutions.
AB  - Recently, four external invertase isoforms (EINV1, EINV2, EINV3, and EINV4) have
      been isolated from S. cerevisiae. However, there is nothing known about their
      structural features and thermodynamics of unfolding. Since this information is
      essential for understanding their functioning at the molecular level as well as
      applicable in the food industry, we investigated guanidinium-chloride induced
      structural changes of the isoforms by CD and fluorescence spectroscopy. The
      resulting unfolding curves measured for each isoform at different temperatures
      were described simultaneously by a reversible two-state model to obtain the
      corresponding thermodynamic parameters. Here, we show that they are different for
      different isoforms and demonstrate that they correlate with the surface charge
      density of the native isoforms which follows the order EINV1 < EINV2 < EINV3 <
      EINV4. It appears that at physiological temperatures the thermodynamic stability
      of the isoforms follows the same order, while above 55  degrees C, the order is
      the opposite EINV1 > EINV2 > EINV3 ~ EINV4. This suggests that increasing the
      efficiency of the food industry processes involving invertase would require the
      application of EINV3 and/or EINV4 at physiological temperatures and EINV1 at
      elevated temperatures.

PMID- 21182262
TI  - Structural characterization of partially disordered human Chibby: insights into
      its function in the Wnt-signaling pathway.
AB  - The Wnt/beta-catenin signaling pathway is critical to embryonic development as
      well as adult tissue regeneration. Dysregulation of this pathway can lead to a
      variety of human diseases, in particular cancers. Chibby (Cby), a small and
      highly conserved protein, plays an antagonistic role in Wnt signaling by
      inhibiting the binding of beta-catenin to Tcf/Lef family proteins, a protein
      interaction that is essential for the transcriptional activation of Wnt target
      genes. Cby is also involved in regulating intracellular distribution of beta
      catenin. Phosphorylated Cby forms a ternary complex with 14-3-3 protein and beta
      catenin, facilitating the export of beta-catenin from the nucleus. On the other
      hand, the antagonistic function of Cby is inhibited upon binding to thyroid
      cancer-1 (TC-1). To dissect the structure-function relationship of Cby, we have
      used NMR spectroscopy, ESI-MS, CD, and DLS to extensively characterize the
      structure of human Cby. Our results show that the 126-residue Cby is partially
      disordered under nondenaturing conditions. While the N-terminal portion of the
      protein is predominantly unstructured in solution, the C-terminal half of Cby
      adopts a coiled-coil structure through self-association. Initial data for the
      binding studies of Cby to 14-3-3zeta (one of the isoforms in the 14-3-3 family)
      and TC-1 via these two distinct structural modules have also been obtained. It is
      noteworthy that in a recent large-scale analysis of the intrinsically disordered
      proteome of mouse, a substantial number of disordered proteins are predicted to
      have coiled-coil motif presence in their sequences. The combination of these two
      molecular recognition features could facilitate disordered Cby in assembling
      protein complexes via different modes of interaction.

PMID- 21182264
TI  - Accurate O-H bond dissociation energy differences of hydroxylamines determined by
      EPR spectroscopy: computational insight into stereoelectronic effects on BDEs and
      EPR spectral parameters.
AB  - Differences in O-H bond dissociation enthalpies (DeltaBDEs) between the
      hydroxylamine of (15)N-labeled TEMPONE and 10 N,N-di-tert-alkyl hydroxylamines
      were determined by EPR. These DeltaBDEs, together with the g and a(N) values of
      the derived nitroxide radicals, are discussed in relation to various geometric,
      intramolecular dipole/dipole, and steric effects and in relation to the results
      from DFT calculations. We find that dipole/dipole interactions are the dominant
      factors in dictating a(N) values and O-H BDEs in all of these structurally
      similar nitroxides and hydroxylamines, respectively. The importance of including
      the Boltzmann distribution of conformations for each nitroxide in the a(N)
      calculations is emphasized.

PMID- 21182263
TI  - Systematic proteome analysis identifies transcription factor YY1 as a direct
      target of miR-34a.
AB  - MicroRNA 34a (miR-34a) is a potential tumor suppressor gene and has been
      identified as a miRNA component of the p53 network. To better understand the
      biological pathways involved in miR-34a action, a parallel global protein and
      mRNA expression profiling on miR-34a treated neuroblastoma cells (IMR32) was
      performed using isotope-coded affinity tags (ICAT) and Affymetrix U133plus2
      microarray, respectively. Global profiling showed that miR-34a causes much
      smaller mRNA expression changes compared to changes at the protein level. A total
      of 1495 proteins represented by two or more peptides were identified from the
      quantitative ICAT analysis, of which 143 and 192 proteins are significantly up-
      or down-regulated by miR-34a, respectively. Pathway analysis of these
      differentially expressed proteins showed the enrichment of apoptosis and cell
      death processes in up-regulated proteins but DNA replication and cell cycle
      processes in the down-regulated proteins. Ribosomal proteins are the most
      significant set down-regulated by miR-34a. Additionally, biological network
      analysis to identify direct interactions among the differentially expressed
      proteins demonstrated that the expression of the ubiquitous transcription factor
      YY1, as well as its downstream proteins, is significantly reduced by miR-34a. We
      further demonstrated that miR-34a directly targets YY1 through a miR-34a-binding
      site within the 3' UTR of YY1 using a luciferase reporter system. YY1 is a
      negative regulator of p53, and it plays an essential role in cancer biology.
      Therefore, YY1 is another important direct target of miR-34a which closely
      regulates TP53 activities.

PMID- 21182265
TI  - Synthesis of 2-azaanthracenes via a sequential Sonogashira coupling/alkynyl imine
      allenyl imine isomerization/aza-Diels-Alder/elimination-aromatization reaction.
AB  - An interesting sequential Sonogashira coupling/alkynyl imine-allenyl imine
      isomerization/aza-Diels-Alder/elimination-aromatization reaction, providing a
      facile synthesis of substituted 2-azaanthracenes from 1,6-diynes and imidoyl
      chlorides, is reported. The easy procedure accessing the products efficiently
      from readily available starting materials may imply a potential synthetic
      application.

PMID- 21182266
TI  - Substitutent effects in the periphery of 2,9-bisaryl-tetraazaperopyrene dyes.
AB  - A series of 2,9-bisaryl-1,3,8,10-tetraazaperopyrene (TAPP) derivatives has been
      synthesized by reacting 4,9-diamino-3,10-perylenequinone diimine with a large
      excess of the corresponding benzoyl chloride in refluxing nitrobenzene. Among all
      derivatives only ortho-substituted phenyl congeners were sufficiently soluble for
      studying solutions of defined concentration in organic solvents. The molecular
      structures of the crystallized compounds, determined by X-ray diffraction of four
      derivatives, are determined by the planar tetraazaperopyrene core and the
      interplanar angle of the phenyl rings, which depends on the size of the ortho
      substituent (40-70 degrees ). The intermolecular packing pattern of all compounds
      is characterized by parallel stacks of molecules with the substituted phenyl
      rings rotated out of the peropyrene plane to reduce the steric repulsion.
      Crystals of a TAPP derivative suitable for X-ray diffraction were grown from
      trifluoroacetic acid (TFA) for the first time, establishing a 2-fold protonated
      species. The ground-state geometries of the TAPP derivatives were calculated by
      DFT [B3PW91/6-31g(d,p)] and the lowest unoccupied molecular orbital (LUMO)
      energies of derivatives possessing electron-withdrawing groups were decreased, as
      were the computed electron affinities. The results of the modeling study were
      confirmed experimentally by cyclic voltammetry to evaluate the substituent
      effects on the highest occupied molecular orbital (HOMO) and the LUMO of the
      peropyrene core. The UV-vis absorption spectra of all compounds recorded in
      trifluoroacetic acid are almost superimposable and display a characteristic
      visible absorption band between 460 and 490 nm (log epsilon = 4.64-5.01) with a
      strong vibrational progression of 1173-1475 cm(-1). Their fluorescence spectra
      are characterized by bands between 490 and 530 nm that are the mirror images of
      the absorption spectra (Stokes shifts of 10-50 nm). The luminescence quantum
      yields range from <0.01 to 0.30, thereby indicating a quenching effect for some
      substitution patterns.

PMID- 21182267
TI  - Bridging interactions and selective nanoparticle aggregation mediated by
      monovalent cations.
AB  - Selective aggregation and precipitation of like-charged nanoparticles (NPs)
      covered with carboxylate ligands can be induced by different monovalent cations.
      The ordering of critical concentrations required for NP precipitation is Cs(+) ?
      K(+) > Li(+) > Na(+) > Rb(+) and does not correlate with the size of hydrated
      cations M(+), nor can it be predicted by the Hofmeister series. On the other
      hand, different anions have no effect on the precipitation trends. These
      observations are rationalized by a theoretical model combining the elements of
      the DLVO theory with molecular-level calculations. The key component of the model
      is the cation-specific binding of various metal cations to the carboxylate
      ligands.

PMID- 21182268
TI  - Double-threaded dimer and supramolecular oligomer formed by stilbene modified
      cyclodextrin: effect of acyl migration and photostimuli.
AB  - We observed changing supramolecular structures of stilbene-alpha-cyclodextrin
      (StiO-alpha-CD) by photoirradiation and migration. Stilbene derivatives show
      photoinduced isomerization under irradiation with lambda = 340 nm to give 2-cis
      StiO-alpha-CD and with lambda = 254 nm to give 2-trans-StiO-alpha-CD.
      Photoisomerization of StiO-alpha-CD shows the photostationary state during 30
      min. 2D NMR and diffusion coefficient studies revealed that 2-trans-StiO-alpha-CD
      forms a double-threaded dimer but 2-cis-StiO-alpha-CD changes to a supramolecular
      oligomer by photoirradiation. We found that the mutual migration of a stilbene
      group (StiO) on alpha-CD occurs under neutral conditions. The StiO group of alpha
      CD (StiO-alpha-CD) moves between the C2 and C3 positions on the secondary
      hydroxyl group of StiO-alpha-CD (the wider rim of alpha-CD) to give 3-trans-StiO
      alpha-CD. 3-trans-StiO-alpha-CD forms a supramolecular oligomer, whereas 3-cis
      StiO-alpha-CD changes to a double-threaded dimer, indicating that 3-StiO-alpha
      CDs gives the opposite results in the supramolecular structures of 2-StiO-alpha
      CDs. The thermal isomerization (migration) is very slow. It takes about 300 h to
      reach the equilibrium state. Moreover, the migration rate constant (k(trans3->2))
      of the trans-StiO group from the C3 position to the C2 position of alpha-CD is
      faster than k(trans2->3) from the C2 position to the C3 position of alpha-CD. On
      the other hand, k(cis2->3) of the cis-StiO group from the C2 position to the C3
      position of alpha-CD is faster than k(cis3->2) from the C3 position to the C2
      position, meaning k(cis2->3) > k(cis3->2), which is the opposite result for
      k(trans3->2) > k(trans2->3). The formation of a stable double-threaded dimer
      would suppress the migration of the StiO group of StiO-alpha-CDs in aqueous
      solutions.

PMID- 21182269
TI  - Routes of pi-electron delocalization in 4-substituted-1,2-benzoquinones.
AB  - The substituent effect in 4-substituted-1,2-benzoquinone is investigated by means
      of modeling using B3LYP hybrid functional in conjunction with the 6-311+G(d,p)
      basis set. The interrelation between different types of substituents, X = NO,
      NO(2), CN, CHO, H, Me, OMe, OH, NH(2), NHMe and N(Me)(2), and both CO groups has
      been characterized both qualitatively and then quantitatively by means of several
      measures of pi-electron delocalization (HOMA, MCI, DI, FLU) based on structural
      and electronic properties of 4-substituted-1,2-benzoquinones chosen for analysis.
      Results of this analysis clearly show that only the meta-placed CO group is
      affected by substituents, whereas the para-placed CO group is rather insensitive
      to substitution. These observations may help to explain diversified chemical
      properties (including reactivity) of CO centers in o-benzoquinone derivatives.
      Among others, they may explain differences in proton-accepting properties of
      carbonyl O atoms, as it is shown for simple models in which carbonyl groups in o
      benzoquinone act as proton acceptors in H-bonds of O...H-F type.

PMID- 21182270
TI  - Synthesis of functionalized dihydrothiophenes from doubly activated cyclopropanes
      using tetrathiomolybdate as the sulfur transfer reagent.
AB  - A number of doubly activated cyclopropanes were synthesized starting from various
      substituted bromosulfonium bromides in good yield. Regioselective ring-opening of
      cyclopropanes with tetrathiomolybdate as the sulfur transfer reagent gave
      dihydrothiophenes in excellent yield.

PMID- 21182271
TI  - Iodine-induced regioselective C-C and C-N bonds formation of N-protected indoles.
AB  - A mild, metal-free, and environmently benign iodine-promoted regioselective C-C
      and C-N bonds formation of N-protected indole derivatives giving 2,3'-biindoles 2
      and 4-(1H-indol-2-yl)morpholines 4 is successfully demonstrated. Various
      bioactive 2,3'-biindoles and 4-(1H-indol-2-yl)morpholines, bearing electron-rich
      to moderately electron-poor substituents, can be prepared in moderate to good
      yields.

PMID- 21182272
TI  - Asymmetric synthesis of sterically and electronically demanding linear omega
      trifluoromethyl containing amino acids via alkylation of chiral equivalents of
      nucleophilic glycine and alanine.
AB  - An operationally convenient, scalable asymmetric synthesis of linear, omega
      trifluoromethyl-containing amino acids, which were not previously produced in
      their enantiomerically pure form, has been developed via alkylation of chiral
      equivalents of nucleophilic glycine and alanine. The simplicity of the
      experimental procedures and high stereochemical outcome (yields up to 90% and
      diastereoselectivity up to 99%) of the presented method render these fluorinated
      amino acids readily available for systematic medicinal chemistry studies and de
      novo peptide design.

PMID- 21182273
TI  - Enhancing cell recognition by scrutinizing cell surfaces with a nanoparticle
      array.
AB  - We report a dual-ligand nanoparticle array approach for discerning cells that
      have different surface receptor profiles surrounding a common primary receptor
      expressed at high or low levels. The achieved differentiation provides
      nanoparticles the ability for potential applications in treatment of patients at
      a personalized medicine level for drug delivery and radiation therapy with a much
      better safety profile.

PMID- 21182274
TI  - Pyrolytic decomposition of ammonia borane to boron nitride.
AB  - The thermal decomposition of ammonia borane was studied using a variety of
      methods to qualitatively identify gas and remnant solid phase species after
      thermal treatments up to 1500  degrees C. At about 110  degrees C, ammonia borane
      begins to decompose yielding H(2) as the major gas phase product. A two step
      decomposition process leading to a polymeric -[NH?BH](n)- species above 130 
      degrees C is generally accepted. In this comprehensive study of decomposition
      pathways, we confirm the first two decomposition steps and identify a third
      process initiating at 1170  degrees C which leads to a semicrystalline hexagonal
      phase boron nitride. Thermogravimetric analysis (TGA) was used to identify the
      onset of the third step. Temperature programmed desorption-mass spectroscopy (TPD
      MS) and vacuum line methods identify molecular aminoborane (H(2)N?BH(2)) as a
      species that can be released in appreciable quantities with the other major
      impurity, borazine. Attenuated total reflectance Fourier transform infrared
      spectroscopy (ATR-FTIR) was used to identify the chemical states present in the
      solid phase material after each stage of decomposition. The boron nitride product
      was examined for composition, structure, and morphology using scanning Auger
      microscopy (SAM), powder X-ray diffraction (XRD), and field emission scanning
      electron microscopy (FESEM). Thermogravimetric Analysis-Mass Spectroscopy (TGA
      MS) and Differential Scanning Calorimetry (DSC) were used to identify the onset
      temperature of the first two mass loss events.

PMID- 21182276
TI  - Palladium hydroxide catalyzed isomerization of primary allylic alcohols to
      aldehydes: application to the formal synthesis of (-)-brevisamide.
AB  - The Pd-catalyzed isomerization of primary allylic alcohols into the corresponding
      saturated aldehydes has been achieved at room temperature for the first time in
      good to excellent yields under mild conditions. The functional group
      compatibility in this reaction is studied, and this new methodology has been
      successfully applied in the synthesis of a C5-C13 tetrahydropyran ring system of
      (-)-brevisamide in seven steps.

PMID- 21182275
TI  - Engineering encodable lanthanide-binding tags into loop regions of proteins.
AB  - Lanthanide-binding tags (LBTs) are valuable tools for investigation of protein
      structure, function, and dynamics by NMR spectroscopy, X-ray crystallography, and
      luminescence studies. We have inserted LBTs into three different loop positions
      (denoted L, R, and S) of the model protein interleukin-1beta (IL1beta) and varied
      the length of the spacer between the LBT and the protein (denoted 1-3).
      Luminescence studies demonstrate that all nine constructs bind Tb3+ tightly in
      the low nanomolar range. No significant change in the fusion protein occurs from
      insertion of the LBT, as shown by two X-ray crystallographic structures of the
      IL1beta-S1 and IL1beta-L3 constructs and for the remaining constructs by
      comparing the 1H-15N heteronuclear single-quantum coherence NMR spectra with that
      of the wild-type IL1beta. Additionally, binding of LBT-loop IL1beta proteins to
      their native binding partner in vitro remains unaltered. X-ray crystallographic
      phasing was successful using only the signal from the bound lanthanide. Large
      residual dipolar couplings (RDCs) could be determined by NMR spectroscopy for all
      LBT-loop constructs and revealed that the LBT-2 series were rigidly incorporated
      into the interleukin-1beta structure. The paramagnetic NMR spectra of loop-LBT
      mutant IL1beta-R2 were assigned and the Deltachi tensor components were
      calculated on the basis of RDCs and pseudocontact shifts. A structural model of
      the IL1beta-R2 construct was calculated using the paramagnetic restraints. The
      current data provide support that encodable LBTs serve as versatile biophysical
      tags when inserted into loop regions of proteins of known structure or predicted
      via homology modeling.

PMID- 21182277
TI  - Arginine-specific modification of proteins with polyethylene glycol.
AB  - In this study, the residue-selective modification of proteins with polymers at
      arginine residues is reported. The difficulty in modifying arginine residues lies
      in the fact that they are less reactive than lysine residues. Consequently,
      typical chemo-selective reactions which employ "kinetic" selectivity (active
      esters, Michael addition, etc.) cannot be used to target these residues. The
      chemistry exploited herein relies on "thermodynamic" selectivity to achieve
      selective modification of arginine residues. omega-Methoxy poly(ethylene glycol)
      bearing an alpha-oxo-aldehyde group was synthesized and used to demonstrate the
      selective modification of lysozyme at arginine residues. In addition, the
      optimization of reaction conditions for coupling as well as the stability of the
      formed adduct toward dilution, toward a nucleophilic buffer, and toward
      acidification are reported. It was concluded that this approach is a convenient,
      mild, selective, and catalyst-free method for protein modification.

PMID- 21182278
TI  - Influence of polyethyleneimine graftings of multi-walled carbon nanotubes on
      their accumulation and elimination by and toxicity to Daphnia magna.
AB  - Modifications of carbon nanotubes (CNTs) for different applications may change
      their physicochemical properties such as surface charge. Assessments of the
      extent to which such modifications influence CNT ecotoxicity, accumulation, and
      elimination behaviors are needed to understand potential environmental risks
      these variously modified nanoparticles may pose. We have modified carbon-14
      labeled multi-walled carbon nanotubes (MWNTs) with polyethyleneimine (PEI)
      surface coatings to increase their aqueous stability and to give them positive,
      negative, or neutral surface charges. Uptake and elimination behaviors of Daphnia
      magna exposed to PEI-coated and acid-modified MWNTs at concentrations of
      approximately 25 and 250 MUg/L were quantified. PEI surface coatings did not
      appear to substantially impact nanotube accumulation or elimination rates.
      Although the PEI-modified nanotubes exhibited enhanced stability in aqueous
      solutions, they appeared to aggregate in the guts of D. magna in a manner similar
      to acid-treated nanotubes. The MWNTs were almost entirely eliminated by Daphnia
      fed algae during a 48 h elimination experiment, whereas elimination without
      feeding was typically minimal. Finally, PEI coatings increased MWNT toxicities,
      though this trend corresponded to the size of the PEI coatings, not their surface
      charges.

PMID- 21182279
TI  - High throughput assay of diffusion through Cx43 gap junction channels with a
      microfluidic chip.
AB  - This paper describes a microfluidic-based assay capable of measuring gap-junction
      mediated dye diffusion in cultured cells. The technique exploits multistream
      laminar flow to selectively expose cells to different environments, enabling
      continuous loading of cells in one compartment while monitoring, in real time,
      dye diffusion into cells of a neighboring compartment. A simple one-dimensional
      diffusion model fit to the data extracted the diffusion coefficient of four
      different dyes, 5-(6)-carboxyfluorescein, 5-chloromethylfluorescein, Oregon green
      488 carboxylic acid, and calcein. Different inhibitors were assayed for their
      ability to reduce dye coupling. The chip can screen multiple inhibitors in
      parallel in the same cell preparation, demonstrating its potential for high
      throughput. The technique provides a convenient method to measure gap junction
      mediated diffusion and a screen for drugs that affect gap junction communication.

PMID- 21182281
TI  - Interaction tensors and local dynamics in common structural motifs of nitrogen: a
      solid-state 14N NMR and DFT study.
AB  - (14)N solid-state NMR powder patterns have been obtained at high field (21.1 T)
      using broadband, frequency-swept pulses and a piecewise acquisition method. This
      approach allowed the electric field gradient (EFG) tensor parameters to be
      obtained from model organic and inorganic systems featuring spherically
      asymmetric nitrogen environments (C(Q) values of up to ca. 4 MHz). The advantages
      and limitations of this experimental approach are discussed, and the observation
      of (14)N T(2) relaxation anisotropy in certain systems is also reported, which
      can shed light on dynamic processes, allowing motional geometries and jump rates
      to be probed. In particular, we show that observable effects of dynamics on (14)N
      spectra can be mediated by modulation of either the EFG tensor or heteronuclear
      dipolar couplings. It is demonstrated that the QCPMG protocol can be used to
      selectively enhance certain types of nitrogen environments on the basis of
      differences in T(2). We also present the results of extensive density functional
      theory calculations on these systems, which show remarkably good correlation with
      the experimental results and allow the prediction of tensor orientations,
      assignment of parameters to crystallographic sites, and a rationalization of the
      origin of the EFG tensors in terms of contributions from individual molecular
      orbitals. This work demonstrates that ultra-wideline (14)N solid-state NMR can,
      under favorable circumstances, be a straightforward, useful, and informative
      probe of molecular structure and dynamics.

PMID- 21182280
TI  - Use of 2,3,5-F(3)Y-beta2 and 3-NH(2)Y-alpha2 to study proton-coupled electron
      transfer in Escherichia coli ribonucleotide reductase.
AB  - Escherichia coli ribonucleotide reductase is an alpha2beta2 complex that
      catalyzes the conversion of nucleoside 5'-diphosphates (NDPs) to deoxynucleotides
      (dNDPs). The active site for NDP reduction resides in alpha2, and the essential
      diferric-tyrosyl radical (Y(122)(*)) cofactor that initiates transfer of the
      radical to the active site cysteine in alpha2 (C(439)), 35 A removed, is in
      beta2. The oxidation is proposed to involve a hopping mechanism through aromatic
      amino acids (Y(122) -> W(48) -> Y(356) in beta2 to Y(731) -> Y(730) -> C(439) in
      alpha2) and reversible proton-coupled electron transfer (PCET). Recently, 2,3,5
      F(3)Y (F(3)Y) was site-specifically incorporated in place of Y(356) in beta2 and
      3-NH(2)Y (NH(2)Y) in place of Y(731) and Y(730) in alpha2. A pH-rate profile with
      F(3)Y(356)-beta2 suggested that as the pH is elevated, the rate-determining step
      of RNR can be altered from a conformational change to PCET and that the altered
      driving force for F(3)Y oxidation, by residues adjacent to it in the pathway, is
      responsible for this change. Studies with NH(2)Y(731(730))-alpha2, beta2, CDP,
      and ATP resulted in detection of NH(2)Y radical (NH(2)Y(*)) intermediates capable
      of dNDP formation. In this study, the reaction of F(3)Y(356)-beta2, alpha2, CDP,
      and ATP has been examined by stopped-flow (SF) absorption and rapid freeze quench
      electron paramagnetic resonance spectroscopy and has failed to reveal any radical
      intermediates. The reaction of F(3)Y(356)-beta2, CDP, and ATP has also been
      examined with NH(2)Y(731)-alpha2 (or NH(2)Y(730)-alpha2) by SF kinetics from pH
      6.5 to 9.2 and exhibited rate constants for NH(2)Y(*) formation that support a
      change in the rate-limiting step at elevated pH. The results together with
      kinetic simulations provide a guide for future studies to detect radical
      intermediates in the pathway.

PMID- 21182282
TI  - Quantum dot-based local field imaging reveals plasmon-based interferometric logic
      in silver nanowire networks.
AB  - We show that the local electric field distribution of propagating plasmons along
      silver nanowires can be imaged by coating the nanowires with a layer of quantum
      dots, held off the surface of the nanowire by a nanoscale dielectric spacer
      layer. In simple networks of silver nanowires with two optical inputs, control of
      the optical polarization and phase of the input fields directs the guided waves
      to a specific nanowire output. The QD-luminescent images of these structures
      reveal that a complete family of phase-dependent, interferometric logic functions
      can be performed on these simple networks. These results show the potential for
      plasmonic waveguides to support compact interferometric logic operations.

PMID- 21182283
TI  - Nanometer scale spectral imaging of quantum emitters in nanowires and its
      correlation to their atomically resolved structure.
AB  - We report the spectral imaging in the UV to visible range with nanometer scale
      resolution of closely packed GaN/AlN quantum disks in individual nanowires using
      an improved custom-made cathodoluminescence system. We demonstrate the
      possibility to measure full spectral features of individual quantum emitters as
      small as 1 nm and separated from each other by only a few nanometers and the
      ability to correlate their optical properties to their size, measured with atomic
      resolution. The direct correlation between the quantum disk size and emission
      wavelength provides evidence of the quantum confined Stark effect leading to an
      emission below the bulk GaN band gap for disks thicker than 2.6 nm. With the help
      of simulations, we show that the internal electric field in the studied quantum
      disks is smaller than what is expected in the quantum well case. We show evidence
      of a clear dispersion of the emission wavelengths of different quantum disks of
      identical size but different positions along the wire. This dispersion is
      systematically correlated to a change of the diameter of the AlN shell coating
      the wire and is thus attributed to the related strain variations along the wire.
      The present work opens the way both to fundamental studies of quantum confinement
      in closely packed quantum emitters and to characterizations of optoelectronic
      devices presenting carrier localization on the nanometer scale.

PMID- 21182284
TI  - Survey of the phosphorylation status of the Schizosaccharomyces pombe
      deubiquitinating enzyme (DUB) family.
AB  - Ubiquitination plays a role in virtually every cellular signaling pathway ranging
      from cell cycle control to DNA damage response to endocytosis and gene
      regulation. The bulk of our knowledge of the ubiquitination system is centered on
      modification of specific substrate proteins and the enzymatic cascade of
      ubiquitination. Our understanding of the regulation of the reversal of these
      modifications (deubiquitination) lags significantly behind. We recently reported
      a multifaceted study of the fission yeast Schizosaccharomyces pombe DUBs
      including characterization of their binding partners, in vitro enzymatic activity
      and subcellular localization. (1) Over half of the 20 fission yeast DUBs have a
      stable protein partner and some of those partners regulate the localization
      and/or activity of their cognate DUB. As a next step in understanding how DUBs
      might otherwise be regulated, we investigated the phosphostatus of the entire
      fission yeast DUB family using LC-MS/MS, and here we discuss the possible
      implications of phosphoregulation.

PMID- 21182285
TI  - Combined speciation analysis by X-ray absorption near-edge structure
      spectroscopy, ion chromatography, and solid-phase microextraction gas
      chromatography-mass spectrometry to evaluate biotreatment of concentrated
      selenium wastewaters.
AB  - In this study we evaluate the potential of anaerobic granular sludge as an
      inoculum for the bioremediation of selenium-contaminated waters using species
      specific analytical methods. Solid species formed by microbial reduction were
      investigated using X-ray absorption near-edge structure (XANES) spectroscopy at
      the selenium K-edge. Furthermore, dissolved selenium species were specifically
      determined by ion chromatography (IC) and solid-phase microextraction gas
      chromatography-mass spectrometry (SPME-GC-MS). Least-squares linear combination
      of the XANES spectra for samples incubated with the highest selenate/selenite
      concentrations (10(-3) M) show the predominance of elemental selenium and a Se(
      I) selenide, such as ferroselite, the thermodynamically most stable iron
      selenide. In contrast, elemental selenium and Se(-II) selenides are the main
      species detected at the lower selenate/selenite concentrations. In each repeated
      fed batch incubation, most aqueous selenite anions were converted into solid
      selenium species, regardless of the type of electron donor used (acetate or
      H(2)/CO(2)) and the selenium concentration applied. On the other hand, at higher
      concentrations of selenate (10(-4) and 10(-3) M), significant amounts of the
      oxyanion remained unconverted after consecutive incubations. SPME-GC-MS
      demonstrated selenium alkylation with both electron donors investigated, as
      dimethyl selenide (DMSe) and dimethyl diselenide (DMDSe). Selenite was even more
      alkylated in the presence of H(2)/CO(2) (maximum 2156 MUg of Se/L of DMSe +
      DMDSe) as compared to acetate (maximum 50 MUg of Se/L). In contrast, selenate was
      less alkylated using both electron donors (maximum 166 and 3 MUg of Se/L,
      respectively). The high alkylation potential for selenite limits its
      bioremediation in selenium laden waters involving H(2)/CO(2) as the electron
      donor despite the fact that nontoxic elemental selenium and thermodynamically
      stable metal selenide species are formed.

PMID- 21182286
TI  - Three-dimensional morphology and crystallography of gold nanorods.
AB  - We determine the three-dimensional shape, to within 1 nm resolution, of single
      crystal gold nanorods grown in the presence of silver ions using electron
      tomography and thickness profile measurements. We find that, contrary to the
      current literature, the octagonal side-facets are sparsely packed atomic planes
      all belonging to the same symmetry-equivalent family, {0 5 12}. Furthermore, the
      rod ends terminate in a pyramid with slightly different facets, and each pyramid
      is connected to the sides by four small {0 5 12} "bridging" facets.

PMID- 21182287
TI  - Dehalorespiration model that incorporates the self-inhibition and biomass
      inactivation effects of high tetrachloroethene concentrations.
AB  - In the vicinity of dense nonaqueous phase liquid (DNAPL) contaminant source
      zones, aqueous concentrations of tetrachloroethene (PCE) in groundwater may
      approach saturation levels. In this study, the ability of two PCE-respiring
      strains (Desulfuromonas michiganensis and Desulfitobacterium strain PCE1) to
      dechlorinate high concentrations of PCE was experimentally evaluated and depended
      on the initial biomass concentration. This suggests high PCE concentrations
      permanently inactivated a fraction of biomass, which, if sufficiently large,
      prevented dechlorination from proceeding. The toxic effects of PCE were
      incorporated into a model of dehalorespirer growth by adapting the transformation
      capacity concept previously applied to describe biomass inactivation by products
      of cometabolic TCE oxidation. The inactivation growth model was coupled to the
      Andrews substrate utilization model, which accounts for the self-inhibitory
      effects of PCE on dechlorination rates, and fit to the experimental data. The
      importance of incorporating biomass inactivation and self-inhibition effects when
      modeling reductive dechlorination of high PCE concentrations was demonstrated by
      comparing the goodness-of-fit of the Andrews biomass inactivation and three
      alternate models that do capture these factors. The new dehalorespiration model
      should improve our ability to predict contaminant removal in DNAPL source zones
      and determine the inoculum size needed to successfully implement bioaugmentation
      of DNAPL source zones.

PMID- 21182288
TI  - Spectral signatures of four-coordinated sites in water clusters: infrared
      spectroscopy of phenol-(H2O)n (~20 <= n <= ~50).
AB  - We report infrared spectra of phenol-(H(2)O)(n) (~20 <= n <= ~50) in the OH
      stretching vibrational region. Phenol-(H(2)O)(n) forms essentially the same
      hydrogen bond (H-bond) network as that of the neat water cluster, (H(2)O)(n+1).
      The phenyl group enables us to apply the scheme of infrared-ultraviolet double
      resonance spectroscopy combined with mass spectrometry, achieving the moderate
      size selectivity (0 <= Deltan <= ~6). The observed spectra show clear decrease of
      the free OH stretch band intensity relative to that of the H-bonded OH band with
      increasing cluster size n. This indicates increase of the relative weight of four
      coordinated water sites, which have no free OH. Corresponding to the suppression
      of the free OH band, the absorption peak of the H-bonded OH stretch band rises at
      ~3350 cm(-1). This spectral change is interpreted in terms of a signature of four
      coordinated water sites in the clusters.

PMID- 21182289
TI  - Comprehensive proteomic analysis of the effects of purine analogs on human Raji B
      cell lymphoma.
AB  - Cladribine (CdA) and fludarabine (FdAMP) are purine analogs that induce apoptosis
      in chronic lymphocytic leukemia and non-Hodgkin's lymphoma, but the mechanisms
      are undefined. The effects of CdA and fludarabine nucleoside (FdA) on the
      cytosolic, mitochondrial, and nuclear proteomes in human Raji lymphoma cells have
      been determined using two-dimensional fluorescence difference gel electrophoresis
      (DIGE) and mass spectrometry. Differentially abundant proteins have provided new
      insights into CdA- and FdA-induced apoptosis. Treatment with these purine analogs
      induced changes in proteins involved with intermediary metabolism, cell growth,
      signal transduction, protein metabolism, and regulation of nucleic acids.
      Differentially abundant mitochondrial 39S ribosomal protein L50, mTERF domain
      containing protein 1, Chitinase-3 like 2 protein, and ubiquinone biosynthesis
      protein COQ9 have been identified in cells undergoing apoptosis. Up-regulation of
      several stress-associated proteins found in the endoplasmic reticulum (ER)
      including GRP78, ERp57, and ORP150 suggests that purine analog-induced apoptosis
      may result from ER stress and unfolded protein response. While mitochondria
      dependent apoptosis has been associated with purine analog cytotoxicity, the
      likely involvement of the ER stress pathway in CdA- and FdA-induced apoptosis has
      been shown here for the first time.

PMID- 21182290
TI  - Purely heterometallic lanthanide(III) macrocycles through controlled assembly of
      disulfide bonds for dual color emission.
AB  - Lanthanide complexes based on bis(amides) of diethylenetriaminepentaacetic acid
      with thiol functionalities are modified with 2,2'-dipyridyl disulfide to give
      activated complexes that can selectively react with thiol-functionalized
      complexes to form heterometallic lanthanide macrocycles. The preparation and full
      characterization of the polyaminocarboxylate ligands N,N''-bis[p
      thiophenyl(aminocarbonyl)]diethylenetriamine-N,N',N''-triacetic acid (H(3)L(x))
      and the activated N,N''-bis[p
      (pyridyldithio)[phenyl(aminocarbonyl)]]diethylenetriamine-N,N',N''-triacetic acid
      (H(3)L(y)) and the complexes LaL(x), NdL(x), SmL(x), EuL(x), GdL(x), DyL(x),
      TbL(x), ErL(x), and YbL(x) are reported. The luminescence properties of the
      LnL(x) complexes emitting in the visible (where Ln = Dy(3+), Tb(3+), Eu(3+), and
      Sm(3+)) are examined by steady-state and time-resolved photoluminescence, and the
      triplet state energy level of GdL(x) was estimated to be 24 100 cm(-1) from the 0
      0 band of the 77 K phosphorescence spectrum. Near-infrared emission was detected
      for the NdL(x), YbL(x), and ErL(x) complexes, demonstrating the versatility of
      the thiophenol chromophore. The assembly of purely heterometallic EuTbL(x)(2)
      macrocycles by reaction of EuL(x) with TbL(y) was followed by UV-vis absorption
      spectroscopy, monitoring the characteristic absorption peak of pyridyl-2-thione
      at 353 nm. Analysis of the solution by mass spectrometry reveals the formation of
      purely heterometallic macrocycle EuTbL(x)(2). This is in contrast with the
      results obtained by dynamic self-assembly under oxidative conditions, where we
      observe a statistical mixture of macrocyclic complexes of Eu(2)L(x)(2),
      Tb(2)L(x)(2), and EuTbL(x)(2). The EuTbL(x)(2) macrocycle displays dual color
      emission, incorporating the characteristic f-f transitions of Eu(3+) and Tb(3+).
      Investigation into the time-resolved photophysical properties of EuTbL(x)(2)
      reveals energy transfer from Tb(3+) to Eu(3+), facilitated by the different
      conformations of the macrocycle in solution.

PMID- 21182291
TI  - Metal-metal and metal-ligand bonding at a QTAIM catastrophe: a combined
      experimental and theoretical charge density study on the alkylidyne cluster
      Fe3(MU-H)(MU-COMe)(CO)10.
AB  - The charge density in the tri-iron methoxymethylidyne cluster Fe(3)(MU-H)(MU
      COMe)(CO)(10) (1) has been studied experimentally at 100 K and by DFT
      calculations on the isolated molecule using the Quantum Theory of Atoms in
      Molecules (QTAIM). The COMe ligand acts as a nearly symmetric bridge toward two
      of the Fe atoms (Fe-C = 1.8554(4), 1.8608(4) A) but with a much longer
      interaction to the third Fe atom, Fe-C = 2.6762(4) A. Complex 1 provides a
      classic example where topological QTAIM catastrophes render an exact structure
      description ambiguous. While all experimental and theoretical studies agree in
      finding no direct metal-metal interaction for the doubly bridged Fe-Fe vector,
      the chemical bonding between the Fe(CO)(4) unit and the Fe(2)(MU-H)(MU
      COMe)(CO)(6) moiety in terms of conventional QTAIM descriptors is much less
      clear. Bond paths implying direct Fe-Fe interactions and a weak interaction
      between the COMe ligand and the Fe(CO)(4) center are observed, depending on the
      experimental or theoretical density model examined. Theoretical studies using the
      Electron Localizability Indicator (ELI-D) suggest the metal-metal bonding is more
      significant, while the delocalization indices imply that both Fe-Fe bonding and
      Fe...C(alkylidyne) bonding are equally important. The source functions at various
      interfragment reference points are similar and highly delocalized. The potential
      energy surface (PES) for the migration of the alkylidyne group from a MU(2) to a
      semi-MU(3) coordination mode has been explored by DFT calculations on 1 and the
      model complexes M(3)(MU-H)(MU-CH)(CO)(10) (M = Fe, 2; Ru, 3; and Os, 4). These
      calculations confirm a semi-MU(3) bridging mode for the alkylidyne ligand as the
      minimum-energy geometry for compounds 2-4 and demonstrate that, for 1, both Fe-Fe
      and Fe...C(alkylidyne) interactions are important in the cluster bonding. The PES
      between MU(2) and semi-MU(3) alkylidyne coordination for 1 is extremely soft, and
      the interconversion between several topological isomers is predicted to occur
      with almost no energy cost. Analysis of the density rho(r) and the Laplacian of
      the density ?(2)rho(r(b)) in the methoxymethylidyne ligand is consistent with a
      partial pi-bond character of the C-O bond, associated with an sp(2) hybridization
      for these atoms.

PMID- 21182292
TI  - Enhanced adhesion of dopamine methacrylamide elastomers via viscoelasticity
      tuning.
AB  - We present a study on the effects of cross-linking on the adhesive properties of
      bio-inspired 3,4-dihydroxyphenylalanine (DOPA). DOPA has a unique catechol moiety
      found in adhesive proteins in marine organisms, such as mussels and polychaete,
      which results in strong adhesion in aquatic conditions. Incorporation of this
      functional group in synthetic polymers provides the basis for pressure-sensitive
      adhesives for use in a broad range of environments. A series of cross-linked DOPA
      containing polymers were prepared by adding divinyl cross-linking agent ethylene
      glycol dimethacrylate (EGDMA) to monomer mixtures of dopamine methacrylamide
      (DMA) and 2-methoxyethyl acrylate (MEA). Samples were prepared using a solvent
      free microwave-assisted polymerization reaction and compared to a similar series
      of cross-linked MEA materials. Cross-linking with EGDMA tunes the viscoelastic
      properties of the adhesive material and has the advantage of not reacting with
      the catechol group that is responsible for the excellent adhesive performance of
      this material. Adhesion strength was measured by uniaxial indentation tests,
      which indicated that 0.001 mol % of EGDMA-cross-linked copolymer showed the
      highest work of adhesion in dry conditions, but non-cross-linked DMA was the
      highest in wet conditions. The results suggest that there is an optimal cross
      linking degree that displays the highest adhesion by balancing viscous and
      elastic behaviors of the polymer but this appears to depend on the conditions.
      This concentration of cross-linker is well below the theoretical percolation
      threshold, and we propose that subtle changes in polymer viscoelastic properties
      can result in significant improvements in adhesion of DOPA-based materials. The
      properties of lightly cross-linked poly(DMA-co-MEA) were investigated by
      measurement of the frequency dependence of the storage modulus (G') and loss
      modulus (G''). The frequency-dependence of G' and magnitude of G'' showed gradual
      decreases with the fraction of EGDMA. Loosely cross-linked DMA copolymers,
      containing 0% and 0.001 mol % of EGDMA-cross-linked copolymers, displayed
      rheological behavior appropriate for pressure-sensitive adhesives characterized
      by a higher G' at high frequencies and lower G' at low frequencies. Our results
      indicate that dimethacrylate cross-linking of DMA copolymers can be used to
      enhance the adhesive properties of this unique material.

PMID- 21182293
TI  - Development of novel 3D-QSAR combination approach for screening and optimizing B
      Raf inhibitors in silico.
AB  - B-Raf is a member of the RAF family of serine/threonine kinases: it mediates cell
      division, differentiation, and apoptosis signals through the RAS-RAF-MAPK
      pathway. Thus, B-Raf is of keen interest in cancer therapy, such as melanoma. In
      this study, we propose the first combination approach to integrate the
      pharmacophore (PhModel), CoMFA, and CoMSIA models for B-Raf, and this approach
      could be used for screening and optimizing potential B-Raf inhibitors in silico.
      Ten PhModels were generated based on the HypoGen BEST algorithm with the flexible
      fit method and diverse inhibitor structures. Each PhModel was designated to the
      alignment rule and screening interface for CoMFA and CoMSIA models. Therefore,
      CoMFA and CoMSIA models could align and recognize diverse inhibitor structures.
      We used two quality validation methods to test the predication accuracy of these
      combination models. In the previously proposed combination approaches, they have
      a common factor in that the number of training set inhibitors is greater than
      that of testing set inhibitors. In our study, the 189 known diverse series B-Raf
      inhibitors, which are 7-fold the number of training set inhibitors, were used as
      a testing set in the partial least-squares validation. The best validation
      results were made by the CoMFA09 and CoMSIA09 models based on the Hypo09
      alignment model. The predictive r(2)(pred) values of 0.56 and 0.56 were derived
      from the CoMFA09 and CoMSIA09 models, respectively. The CoMFA09 and CoMSIA09
      models also had a satisfied predication accuracy of 77.78% and 80%, and the
      goodness of hit test score of 0.675 and 0.699, respectively. These results
      indicate that our combination approach could effectively identify diverse B-Raf
      inhibitors and predict the activity.

PMID- 21182294
TI  - One-week antihypertensive effect of Ile-Gln-Pro in spontaneously hypertensive
      rats.
AB  - The antihypertensive effect of an angiotensin I-converting enzyme (ACE)
      inhibitory peptide Ile-Gln-Pro (IQP), whose sequence was derived from Spirulina
      platensis , was investigated in spontaneously hypertensive rats (SHRs) for 1
      week. The weighted systolic blood pressure (SBP) and diastolic blood pressure
      (DBP) of the peptide IQP-treated group were significantly lower than those of the
      negative control group from the third and fourth days, respectively. Accompanying
      the blood pressure reduction, a significant regulation of the expression of major
      components of the renin-angiotensin system (RAS) was found in the treatment
      group, including downregulation of the mRNA levels of renin, ACE, and the
      angiotensin II type 1 (AT1) receptor in the kidney, as well as serum
      angiotensinogen (Ang), ACE, and angiotensin II (Ang II) concentrations. The
      treatment group also showed upregulation of mRNA expression of the angiotensin II
      type 2 (AT2) receptor in the kidney. Our findings suggested that IQP might be of
      potential use in the treatment of hypertension.

PMID- 21182295
TI  - Formation and stability of nanofibers from a milk-derived peptide.
AB  - The objective of the present work was to investigate the physicochemical
      conditions that trigger the self-assembly of peptide beta-lg f1-8 and therefore
      lead to nanofibers and hydrogel formation. Nanostructures formed by self-assembly
      of peptide beta-lg f1-8 in the pH range of 2.0-11.0 were studied by transmission
      electron microscopy (TEM). Hydrogel formation was studied as a function of pH and
      resulted in evidence of a link between hydrogel formation and the charge
      distribution carried by the peptide structure. Finally, circular dichroism (CD)
      spectroscopy was used to characterize the effects of peptide concentration (0.4
      2.0 mg/mL), ionic strength (0-1 M NaCl), and temperature (20-80  degrees C) on
      the secondary structure of peptide beta-lg f1-8. Hydrogels were obtained at
      peptide concentrations above 2.5 mg/mL. Peptide concentration and pH adjustment
      were shown to trigger self-assembly of beta-lg f1-8, but increasing ionic
      strength had no effect. Heating to 80  degrees C induced a stronger CD signal
      intensity due to an increase in solubility of the peptide, whereas only slight
      changes in CD pattern were found upon cooling to 20  degrees C. Overall, results
      emphasize the role of particular molecular interactions in beta-sheet self
      assembly of peptide beta-lg f1-8 and pH-dependent electrostatic interactions
      occurring between beta-lg f1-8 units, which can explain its propensity to self
      assembly.

PMID- 21182296
TI  - Coupling of oligomerization and nucleotide binding in the AAA+ chaperone ClpB.
AB  - Members of the family of ATPases associated with various cellular activities
      (AAA+) typically form homohexameric ring complexes and are able to remodel their
      substrates, such as misfolded proteins or protein-protein complexes, in an ATP
      driven process. The molecular mechanism by which ATP hydrolysis is coordinated
      within the multimeric complex and the energy is converted into molecular motions,
      however, is poorly understood. This is partly due to the fact that the oligomers
      formed by AAA+ proteins represent a highly complex system and analysis depends on
      simplification and prior knowledge. Here, we present nucleotide binding and
      oligomer assembly kinetics of the AAA+ protein ClpB, a molecular chaperone that
      is able to disaggregate protein aggregates in concert with the DnaK chaperone
      system. ClpB bears two AAA+ domains (NBD1 and NBD2) on one subunit and forms
      homohexameric ring complexes. In order to dissect individual mechanistic steps,
      we made use of a reconstituted system based on two individual constructs bearing
      either the N-terminal (NBD1) or the C-terminal AAA+ domain (NBD2). In contrast to
      the C-terminal construct, the N-terminal construct does not bind the fluorescent
      nucleotide MANT-dADP in isolation. However, sequential mixing experiments suggest
      that NBD1 obtains nucleotide binding competence when incorporated into an
      oligomeric complex. These findings support a model in which nucleotide binding to
      NBD1 is dependent on and regulated by trans-acting elements from neighboring
      subunits, either by direct interaction with the nucleotide or by stabilization of
      a nucleotide binding-competent state. In this way, they provide a basis for
      intersubunit communication within the functional ClpB complex.

PMID- 21182297
TI  - Dissociation dynamics and thermochemistry of tin species, (CH3)4Sn and (CH3)6Sn2,
      by threshold photoelectron-photoion coincidence spectroscopy.
AB  - The dissociative photoionization of tetramethyltin (Me4Sn) and hexamethylditin
      (Me6Sn2) has been investigated by threshold photoelectron-photoion coincidence
      (TPEPICO). Ions are energy-selected, and their 0 K dissociation onsets are
      measured by monitoring the mass spectra as a function of ion internal energy.
      Me4Sn(+) dissociates rapidly by methyl loss, with a 0 K onset of E0 = 9.382 +/-
      0.020 eV. The hexamethylditin ion dissociates slowly on the time scale of the
      experiment (i.e., during the 40 MUs flight time to the detector) so that
      dissociation rate constants are measured as a function of the ion energy. RRKM
      and the simplified statistical adiabatic channel model (SSACM) are used to
      extrapolate the measured rate constants for methyl and Me3Sn(*) loss to their 0 K
      dissociation onsets, which were found to be 8.986 +/- 0.050 and 9.153 +/- 0.075
      eV, respectively. Updated values for the heats of formation of the neutral Me4Sn
      and Me6Sn2 are used to derive the following 298.15 K gas-phase standard heats of
      formation, in kJ.mol-1: Delta(f)H(m)(o)(Me3Sn(+),g) = 746.3 +/- 2.9;
      Delta(f)H(m)(o)(Me5Sn2(+),g) = 705.1 +/- 7.5; Delta(f)H(m)(o)(Me3Sn(*),g) = 116.6
      +/- 9.7; Delta(f)H(m)(o)(Me2Sn,g) = 123.0 +/- 16.5; Delta(f)H(m)(o)(MeSn(+),g) =
      877.8 +/- 16.4. These energetic values also lead to the following 298.15 K bond
      dissociation enthalpies, in kJ.mol-1: BDE(Me3Sn-Me) = 284.1 +/- 9.9; BDE(Me3Sn
      SnMe3) = 252.6 +/- 14.8.

PMID- 21182298
TI  - Radical SAM activation of the B12-independent glycerol dehydratase results in
      formation of 5'-deoxy-5'-(methylthio)adenosine and not 5'-deoxyadenosine.
AB  - Activation of glycyl radical enzymes (GREs) by S-adenosylmethonine (AdoMet or
      SAM)-dependent enzymes has long been shown to proceed via the reductive cleavage
      of SAM. The AdoMet-dependent (or radical SAM) enzymes catalyze this reaction by
      using a [4Fe-4S] cluster to reductively cleave AdoMet to form a transient 5'
      deoxyadenosyl radical and methionine. This radical is then transferred to the
      GRE, and methionine and 5'-deoxyadenosine are also formed. In contrast to this
      paradigm, we demonstrate that generation of a glycyl radical on the B(12)
      independent glycerol dehydratase by the glycerol dehydratase activating enzyme
      results in formation of 5'-deoxy-5'-(methylthio)adenosine and not 5'
      deoxyadenosine. This demonstrates for the first time that radical SAM activases
      are also capable of an alternative cleavage pathway for SAM.

PMID- 21182299
TI  - Quorum sensing in Gram-negative bacteria: small-molecule modulation of AHL and AI
      2 quorum sensing pathways.

PMID- 21182300
TI  - Antarafacial mediation of oxygen delivery by a phenylsulfinyl group in the
      epoxidation of proximal double bonds: intramolecular trapping of an early
      Pummerer intermediate with stereoelectronic control.
AB  - Stereospecific intramolecular antarafacial epoxidation of a double bond via an
      early Pummerer reaction intermediate has been demonstrated. The intermediate is
      presumably generated via trifluoroacetylation of a sulfoxide precursor.
      Ionization of trifluoroacetate would formally generate a dipositive "sulfenium"
      equivalent. This species attacks an otherwise unactivated, proximal olefinic
      linkage in an antiperiplanar fashion, with trifluoroacetate serving as the
      nucleophile. Proposed mechanistic intermediates were characterized structurally
      (in several cases by crystallographic means) and shown to serve as precursors en
      route to the final antarafacial epoxides. The sense of the cyclization seems to
      be driven by principles inherent in Markovnikov's rule.

PMID- 21182301
TI  - The W232R suppressor mutation promotes maturation of a truncation mutant lacking
      both nucleotide-binding domains and restores interdomain assembly and activity of
      P-glycoprotein processing mutants.
AB  - ATP-binding cassette (ABC) proteins contain two nucleotide-binding domains (NBDs)
      and two transmembrane (TM) domains (TMDs). Interdomain interactions and packing
      of the TM segments are critical for function, and disruption by genetic mutations
      contributes to disease. P-glycoprotein (P-gp) is a useful model to identify
      mechanisms that repair processing defects because numerous arginine suppressor
      mutations have been identified in the TM segments. Here, we tested the prediction
      that a mechanism of arginine rescue was to promote intradomain interactions
      between TM segments and restore interdomain assembly. We found that suppressor
      W232R(TM4/TMD1) rescued mutants with processing mutations in any domain and
      restored defective NBD1-NBD2, NBD1-TMD2, and TMD1-TMD2 interactions. W232R also
      promoted packing of the TM segments because it rescued a truncation mutant
      lacking both NBDs. The mechanism of W232R rescue likely involved intradomain
      hydrogen bond interactions with Asn296(TM5) since only N296A abolished rescue by
      W232R and rescue was only observed when Trp232 was replaced with hydrogen-bonding
      residues. In TMD2, suppressor T945R(TM11) also promoted packing of the TM
      segments because it rescued the truncation mutant lacking the NBDs and suppressed
      formation of alternative topologies. We propose that T945R rescue was mediated by
      interactions with Glu875(TM10) since T945E/E875R promoted maturation while
      T945R/E875A did not.

PMID- 21182302
TI  - DNA-based identification of spices: DNA isolation, whole genome amplification,
      and polymerase chain reaction.
AB  - Usually spices are identified morphologically using simple methods like
      magnifying glasses or microscopic instruments. On the other hand, molecular
      biological methods like the polymerase chain reaction (PCR) enable an accurate
      and specific detection also in complex matrices. Generally, the origins of spices
      are plants with diverse genetic backgrounds and relationships. The processing
      methods used for the production of spices are complex and individual.
      Consequently, the development of a reliable DNA-based method for spice analysis
      is a challenging intention. However, once established, this method will be easily
      adapted to less difficult food matrices. In the current study, several
      alternative methods for the isolation of DNA from spices have been developed and
      evaluated in detail with regard to (i) its purity (photometric), (ii) yield
      (fluorimetric methods), and (iii) its amplifiability (PCR). Whole genome
      amplification methods were used to preamplify isolates to improve the ratio
      between amplifiable DNA and inhibiting substances. Specific primer sets were
      designed, and the PCR conditions were optimized to detect 18 spices selectively.
      Assays of self-made spice mixtures were performed to proof the applicability of
      the developed methods.

PMID- 21182304
TI  - Membrane response model for ion-selective electrodes operated by controlled
      potential thin-layer coulometry.
AB  - The electrochemical response behavior of controlled-potential thin-layer
      coulometric sensors based on solvent polymeric membranes doped with ionophores is
      elucidated by numerical simulation. This treatment forms the theoretical basis
      for the design of potentially recalibration-free ion-selective chemical sensors
      that operate by exhaustive coulometry. Mass transport is assumed to occur
      primarily by diffusion in each bulk phase, and interfacial ion exchange with
      interfering ions is described with modern ion-selective electrode theory. The ion
      selective membrane is assumed to contain an ion exchanger that can form
      concentration gradients as a result of transmembrane ion fluxes. It is shown that
      the diffusion of ions in the membrane phase will become rate limiting for
      membrane components with diffusion coefficients of 10(-8) cm(2) s(-1) that are
      typical for traditional ion-selective electrode formulations. This characteristic
      may be advantageous for sample thicknesses of 20 MUm or less, where otherwise
      exhaustive depletion occurs too quickly to be distinguishable from nonfaradic
      processes. In most other cases, however, it will be necessary to formulate
      membrane materials that permit much faster diffusion characteristics. Indeed, the
      simulations give guidance on sensor design for sample concentrations that
      approach millimolar levels. The treatment also considers interferences from ions
      of the same charge sign as the analyte ion, and it is shown that the required
      selectivity for a given analysis must be about 1 order of magnitude higher than
      in direct potentiometry. This is because the coulometric exhaustive depletion
      process occurs only for the analyte ion, not for the interfering one, and to
      avoid interference, the required selectivity must be maintained even if the
      sample contains a fraction of the original analyte levels.

PMID- 21182303
TI  - A 265-base DNA sequencing read by capillary electrophoresis with no separation
      matrix.
AB  - Electrophoretic DNA sequencing without a polymer matrix is currently possible
      only with the use of some kind of "drag-tag" as a mobility modifier. In free
      solution conjugate electrophoresis (FSCE), a drag-tag attached to each DNA
      fragment breaks linear charge-to-friction scaling, enabling size-based separation
      in aqueous buffer alone. Here we report a 265-base read for free-solution DNA
      sequencing by capillary electrophoresis using a random-coil protein drag-tag of
      unprecedented length and purity. We identified certain methods of protein
      expression and purification that allow the production of highly monodisperse drag
      tags as long as 516 amino acids, which are almost charge neutral (+1 to +6) and
      yet highly water-soluble. Using a four-color LIF detector, 265 bases could be
      read in 30 min with a 267-amino acid drag-tag, on par with the average read of
      current next-gen sequencing systems. New types of multichannel systems that allow
      much higher throughput electrophoretic sequencing should be much more accessible
      in the absence of a requirement for viscous separation matrix.

PMID- 21182305
TI  - Metabolic fingerprinting of biofluids by infrared spectroscopy: modeling and
      optimization of flow rates for laminar fluid diffusion interface sample
      preconditioning.
AB  - The laminar fluid diffusion interface (LFDI) is a microfluidic tool that
      manipulates the composition of liquid mixtures by exploiting differences among
      diffusion coefficients of the dissolved components. One application is the
      preprocessing of (bio)fluids prior to spectroscopic characterization. For
      example, in the case of infrared (IR) spectroscopy, the technique can improve
      sensitivity to low-concentration serum metabolites. The practical benefit is
      "metabolic fingerprinting" measurements that are more sensitive to low
      concentration metabolites than are the counterpart measurements for the original
      serum sample. Optimal use of the LFDI technique has proven elusive, since the
      composition of the product of interest is very sensitive to the choice of flow
      rates for the liquid streams entering and emerging from the LFDI channel. To
      provide the basis for optimal use, this study had the objective of developing a
      simulation package that predicts the composition of the LFDI product, given the
      LFDI structural and operating parameters. To demonstrate the utility of the
      simulations, composition of the LFDI products predicted for two illustrative sets
      of trials were compared with experimental data. The flow rates thus derived
      provided a LFDI product that is relatively rich in serum metabolites, while
      largely depleted of protein, and very well suited for subsequent IR spectroscopic
      characterization.

PMID- 21182306
TI  - Three-dimensional positron emission tomography/computed tomography analysis of
      13NO3- uptake and 13N distribution in growing kohlrabi.
AB  - We report the application of three-dimensional positron emission
      tomography/computed tomography (PET/CT) for the analysis of (13)NO(3)(-) uptake
      and (13)N distribution in growing kohlrabi. The analytical procedures, equipment
      parameters, and image reconstruction mode for plant imaging were tested and
      selected. (13)N in growing kohlrabi plants was imaged versus time using both PET
      movies and PET/CT tomograms. The (13)NO(3)(-) transport velocity in kohlrabi from
      root to petiole was estimated to be 1.0 cm/min. The appearance of shell-shaped
      (13)NO(3)(-) transport pathways, corresponding to the kohlrabi corm, suggests the
      existence of special routes with higher efficiency for (13)NO(3)(-) transport,
      which tends to have the shortest distances to the leaves or buds. Standardized
      uptake values (SUVs), used as the representative figures for describing (13)N
      distribution, were quantified versus time at some putative sites of interest. For
      multiple analysis of the same-plant, (13)N distribution in kohlrabi under normal
      conditions, methionine sulfoximine (MSX) stress, and recovery from MSX stress was
      examined. The (13)N distribution variation studies were also done under the above
      three growth conditions. Our results suggest a significant downregulation of
      nitrate uptake in kohlrabi in the presence of MSX.

PMID- 21182308
TI  - Biochemical characterization of TAK-593, a novel VEGFR/PDGFR inhibitor with a two
      step slow binding mechanism.
AB  - Inhibition of tumor angiogenesis leads to a lack of oxygen and nutrients in the
      tumor and therefore has become a standards of care for many solid tumor
      therapies. Dual inhibition of vascular endothelial growth factor receptor (VEGFR)
      and platelet-derived growth factor receptor (PDGFR) protein kinase activities is
      a popular strategy for targeting tumor angiogenesis. We discovered that TAK-593,
      a novel imidazo[1,2-b]pyridazine derivative, potently inhibits tyrosine kinases
      from the VEGFR and PDGFR families. TAK-593 was highly selective for these
      families, with an IC(50) >1 MUM when tested against more than 200 protein and
      lipid kinases. TAK-593 displayed competitive inhibition versus ATP. In addition,
      TAK-593 inhibited VEGFR2 and PDGFRbeta in a time-dependent manner, classifying it
      as a type II kinase inhibitor. Analysis of enzyme-inhibitor preincubation
      experiments revealed that the binding of TAK-593 to VEGFR2 and PDGFRbeta occurs
      via a two-step slow binding mechanism. Dissociation of TAK-593 from VEGFR2 was
      extremely slow (t(1/2) >17 h), and the affinity of TAK-593 at equilibrium (K(i)*)
      was less than 25 pM. Ligand displacement analysis with a fluorescent tracer
      confirmed the slow dissociation of TAK-593. The dissociation rate constants were
      in good agreement between the activity and ligand displacement data, and both
      analyses supported slow dissociation of TAK-593. The long residence time of TAK
      593 may achieve an extended pharmacodynamic effect on VEGFR2 and PDGFRbeta
      kinases in vivo that differs substantially from its observed pharmacokinetic
      profile.

PMID- 21182307
TI  - Protein kinase CK2 is a central regulator of topoisomerase I hyperphosphorylation
      and camptothecin sensitivity in cancer cell lines.
AB  - Topoisomerase I (topo I) is required to unwind DNA during synthesis and provides
      the unique target for camptothecin-derived chemotherapeutic agents, including
      Irinotecan and Topotecan. While these agents are highly effective anticancer
      agents, some tumors do not respond due to intrinsic or acquired resistance, a
      process that remains poorly understood. Because of treatment toxicity, there is
      interest in identifying cellular factors that regulate tumor sensitivity and
      might serve as predictive biomarkers of therapy sensitivity. Here we identify the
      serine kinase, protein kinase CK2, as a central regulator of topo I
      hyperphosphorylation and activity and cellular sensitivity to camptothecin. In
      nine cancer cell lines and three normal tissue-derived cell lines we observe a
      consistent correlation between CK2 levels and camptothecin responsiveness. Two
      other topo I-targeted serine kinases, protein kinase C and cyclin-dependent
      kinase 1, do not show this correlation. Camptothecin-sensitive cancer cell lines
      display high CK2 activity, hyperphosphorylation of topo I, elevated topo I
      activity, and elevated phosphorylation-dependent complex formation between topo I
      and p14ARF, a topo I activator. Camptothecin-resistant cancer cell lines and
      normal cell lines display lower CK2 activity, lower topo I phosphorylation, lower
      topo I activity, and undetectable topo I/p14ARF complex formation. Experimental
      inhibition or activation of CK2 demonstrates that CK2 is necessary and sufficient
      for regulating these topo I properties and altering cellular responses to
      camptothecin. The results establish a cause and effect relationship between CK2
      activity and camptothecin sensitivity and suggest that CK2, topo I
      phosphorylation, or topo I/p14ARF complex formation could provide biomarkers of
      therapy-responsive tumors.

PMID- 21182310
TI  - Electric field dependent photocurrent decay length in single lead sulfide
      nanowire field effect transistors.
AB  - We determined the minority carrier diffusion length to be ~1 MUm in single PbS
      nanowire field effect transistors by scanning photocurrent microscopy. PbS
      nanowires grown by the vapor-liquid-solid method were p-type with hole mobilities
      up to 49 cm(2)/(V s). We measured a photoresponse time faster than 14 MUs with
      near-unity charge separation efficiency at the contacts. For the first time, we
      also observed a field-dependent photocurrent decay length, indicating a drift
      dominant carrier transport at high bias.

PMID- 21182309
TI  - Processing mechanism and substrate selectivity of the core NuA4 histone
      acetyltransferase complex.
AB  - Esa1, an essential MYST histone acetyltransferase found in the yeast piccolo NuA4
      complex (picNuA4), is responsible for genome-wide histone H4 and histone H2A
      acetylation. picNuA4 uniquely catalyzes the rapid tetra-acetylation of
      nucleosomal H4, though the molecular determinants driving picNuA4 efficiency and
      specificity have not been defined. Here, we show through rapid substrate trapping
      experiments that picNuA4 utilizes a nonprocessive mechanism in which picNuA4
      dissociates from the substrate after each acetylation event. Quantitative mass
      spectral analyses indicate that picNuA4 randomly acetylates free and nucleosomal
      H4, with a small preference for lysines 5, 8, and 12 over lysine 16. Using a
      series of 24 histone mutants of H4 and H2A, we investigated the parameters
      affecting catalytic efficiency. Most strikingly, removal of lysine residues did
      not substantially affect the ability of picNuA4 to acetylate remaining sites, and
      insertion of an additional lysine into the H4 tail led to rapid quintuple
      acetylation. Conversion of the native H2A tail to an H4-like sequence resulted in
      enhanced multisite acetylation. Collectively, the results suggest picNuA4's site
      selectivity is dictated by accessibility on the nucleosome surface, the relative
      proximity from the histone fold domain, and a preference for intervening glycine
      residues with a minimal (n + 2) spacing between lysines. Functionally distinct
      from other HAT families, the proposed model for picNuA4 represents a unique
      mechanism of substrate recognition and multisite acetylation.

PMID- 21182311
TI  - Galvanic porous silicon composites for high-velocity nanoenergetics.
AB  - Porous silicon (PS) films ~65-95 MUm thick composed of pores with diameters less
      than 3 nm were fabricated using a galvanic etching approach that does not require
      an external power supply. A highly reactive, nanoenergetic composite was then
      created by impregnating the nanoscale pores with the strong oxidizer, sodium
      perchlorate (NaClO(4)). The combustion propagation velocity of the energetic
      composite was measured using microfabricated diagnostic devices in conjunction
      with high-speed optical imaging up to 930000 frames per second. Combustion
      velocities averaging 3050 m/s were observed for PS films with specific surface
      areas of ~840 m(2)/g and porosities of 65-67%.

PMID- 21182312
TI  - Transmetalation reactions of a scandium complex supported by a ferrocene diamide
      ligand.
AB  - Efforts to transfer to aluminum the heterocyclic ligand of a ring-opened
      imidazole scandium complex, which was previously reported, are presented. A ring
      opened imidazole aluminum compound was formed at 50  degrees C and characterized
      as a trialuminum complex. At high temperature (85  degrees C), the formation of
      an unusual scandium/aluminum methylidene was observed. The reaction products were
      characterized by standard spectroscopic techniques and X-ray crystallography.
      Density functional theory calculations were used to understand the electronic
      structure of the scandium/aluminum methylidene complex.

PMID- 21182313
TI  - Enhanced photosafety of cinacalcet upon complexation with serum albumin.
AB  - Cinacalcet (CIN) is a calcimimetic drug, which contains a naphthalene chromophore
      and binds almost quantitatively to human serum albumin (HSA). In the present
      work, the excited states of CIN have been characterized in order to obtain
      relevant information about complexation of CIN with HSA. The fluorescence
      spectrum in acetonitrile, at lambda(exc) = 290 nm, displayed two bands with
      maxima at 332 and 439 nm, assigned to the monomer and exciplex emission. Upon
      protonation of the amino group, the exciplex band disappeared, with a concomitant
      increase of the monomer emission intensity. Time-resolved fluorescence evidenced
      an intramolecular dynamic quenching, attributed to exciplex formation and/or
      photoinduced electron transfer, in agreement with the favorable thermodynamics
      predicted by the Rehm-Weller equations. Diffusion controlled dynamic quenching of
      CINH(+) fluorescence by oxygen was observed. The emission properties in PBS were
      similar to those obtained for CINH(+) in acetonitrile. Laser flash photolysis
      (LFP) of CIN and CINH(+) in acetonitrile/N(2), at lambda(exc) = 308 nm, gave rise
      to the naphthalene-like triplet excited states, with maxima at 420 nm and
      lifetimes of 4 and 7 MUs; they were efficiently quenched by oxygen. No
      significant singlet excited state interaction was observed in CINH(+)/HSA
      complexes, as revealed by the emission spectra, which were roughly explained
      taking into account the relative contributions of drug and protein in the
      absorption spectra. Upon LFP of the complexes, triplet excited states were
      generated; the decays monitored at 420 nm were satisfactorily fitted using a
      function containing two monoexponential terms, corresponding to a short-lived
      (tau(1) = 8 MUs) and a long-lived (tau(2) = 37 MUs) component. This indicates
      that the drug is incorporated into two different binding sites of HSA. Despite
      the long triplet lifetimes of the CINH(+)/HSA complexes, the rate constant of
      quenching by oxygen was found to be 2 orders of magnitude lower than that
      determined in acetonitrile, which can be attributed to the relative slower
      diffusion rates in this microheterogeneous system. Therefore, the protein
      microenvironment protects cinacalcet from attack by oxygen; this prevents the
      phototoxic effects caused by formation of singlet oxygen and results in an
      enhanced photosafety of the drug.

PMID- 21182314
TI  - Influence of fluorocarbon and hydrocarbon acyl groups at the surface of bovine
      carbonic anhydrase II on the kinetics of denaturation by sodium dodecyl sulfate.
AB  - This paper examines the influence of acylation of the Lys-epsilon-NH(3)(+) groups
      of bovine carbonic anhydrase (BCA, EC 4.2.1.1) to Lys-epsilon-NHCOR (R = -CH(3), 
      CH(2)CH(3), and -CH(CH(3))(2), -CF(3)) on the rate of denaturation of this
      protein in buffer containing sodium dodecyl sulfate (SDS). Analysis of the rates
      suggested separate effects due to electrostatic charge and hydrophobic
      interactions. Rates of denaturation (k(Ac,n)) of each series of acylated
      derivatives depended on the number of acylations (n). Plots of log k(Ac,n) vs n
      followed U-shaped curves. Within each series of derivatives, rates of
      denaturation decreased as n increased to ~7; this decrease was compatible with
      increasingly unfavorable electrostatic interactions between SDS and protein. In
      this range of n, rates of denaturation also depended on the choice of the acyl
      group as n increased to ~7, in a manner compatible with favorable hydrophobic
      interactions between SDS and the -NHCOR groups. As n increased in the range 7 < n
      < 14, however, rates of denaturation stayed approximately constant; analysis
      suggested that these rates were compatible with an increasingly important
      contribution to denaturation that depended both on the net negative charge of the
      protein and on the hydrophobicity of the R group. The mechanism of denaturation
      thus seems to change with the extent of acylation of the protein. For derivatives
      with the same net electrostatic charge, rates of denaturation increased with the
      acyl group (by a factor of ~3 for n ~ 14) in the order CH(3)CONH- <
      CH(3)CH(2)CONH- < (CH(3))(2)CHCONH- < CF(3)CONH-. These results suggested that
      the hydrophobicity of CF(3)CONH- is slightly greater (by a factor of <2) than
      that of RHCONH- with similar surface area.

PMID- 21182315
TI  - N-aminoazetidinecarboxylic acid: direct access to a small-ring hydrazino acid.
AB  - A short and efficient synthesis of the previously unknown N
      aminoazetidinecarboxylic acid has been established using a photochemical [2 + 2]
      cycloaddition strategy starting from 6-azauracil. Chiral derivatization with a
      nonracemic oxazolidinone provided access to both enantiomers of the title
      product.

PMID- 21182316
TI  - Dynamics of the water hydrogen bond network at ionic, nonionic, and hydrophobic
      interfaces in nanopores and reverse micelles.
AB  - The effects of water confinement on hydrogen bond dynamics and hydrogen bond
      exchange have been analyzed by molecular dynamics simulations for a series of
      different sizes of spherical nanopores of ionic, nonionic, and hydrophobic
      interfaces. We have calculated translational diffusion residence times,
      orientational decay time constants, the infrared spectra, correlation functions
      describing the hydrogen bond network, the hydrogen bond exchange time and rate
      constant, and ensemble averages of the hydrogen bond exchange reaction
      coordinate. We focus on the interfacial layer and bulklike interior of these
      small water containing nanostructures. Our results indicate a universal slowdown
      in rotational and hydrogen bond dynamics at the interface relative to bulk water.
      The interiors of nanopores with highly charged interfaces undergo qualitatively
      different dynamics than those in other nanopores. The rotational jump hydrogen
      bond exchange mechanism is shown to be robust and universal, even for this
      variety of interfaces. The implications of these results are discussed in terms
      of the role of confinement vs interface structure on water dynamics in nanopores.

PMID- 21182317
TI  - Solubilization of gabapentin into HII mesophases.
AB  - In the present work, we report on the solubilization of gabapentin (GBP) into
      lyotropic hexagonal mesophases composed of monoolein, tricaprylin, and water. It
      was demonstrated that the hexagonal structure remained intact up to 2 wt %
      gabapentin, whereas the lamellar phase coexisted with the hexagonal one in the
      concentration range of 3-4 wt % of the drug. At gabapentin content of 5-6 wt %,
      only lamellar phases containing defects such as dislocations and multilamellar
      vesicles were detected. Incorporation of GBP decreased the lattice parameter of
      the H(II) mesophase from 56.6 to 50.6 A, while the structural dimensions of the
      lamellar phase were not affected. ATR-FTIR analysis suggested enhanced hydrogen
      bonding between the protonated amine of GBP and the O-H groups of the GMO and the
      water surrounding in the inner hydrophilic interface region. This led to
      intercalation of the drug into the water-lipid interface. At higher GBP loads of
      4-6 wt %, thermal analysis revealed disordering within the lipid packing,
      apparently induced by the spatially altered interface area. Rheological
      measurements correlated the macroscopic features of the systems with alterations
      on the molecular level and allowed distinguishing between closely related
      mesophases due to their different rheological characteristics. In vitro
      transdermal delivery studies showed that the examined mesophases enabled a
      sustained release of GBP compared to its aqueous solution. Sustained release was
      more pronounced in the case of the hexagonal mesophase, compared to the lamellar
      one.

PMID- 21182318
TI  - Reactions of HCl and D2O with molten alkali carbonates.
AB  - The acidic oxide SO2 and protic acid HCl are among the gases released in the
      combustion of coal and the incineration of municipal waste. They are typically
      removed by wet or dry scrubbing involving calcium carbonate or calcium hydroxide.
      The molten alkali carbonate eutectic provides a liquid-state alternative that
      readily absorbs SO2 and HCl and does not become covered with a passivating layer.
      Gas-liquid scattering experiments utilizing the eutectic mixture (44 mol %
      Li2CO3, 31 mol % Na2CO3, 25 mol % K2CO3) reveal that the reaction probability for
      HCl(g) + CO32- -> CO2(g) + OH- + Cl- is 0.31 +/- 0.02 at 683 K and rises to 0.39
      at 783 K. Gaseous CO2 is formed within 10-4 s or less, implying that the reaction
      takes place in a liquid depth of less than 1000 A. When the melt is exposed to
      D2O, the analogous reaction D2O(g) + CO32- -> CO2(g) + 2OD- occurs too slowly to
      measure and no water uptake is observed. Together with previous studies of SO2(g)
      + CO32- -> CO2(g) + SO32-, these results demonstrate that molten carbonates
      efficiently remove both gaseous HCl and SO2 while reacting at most weakly with
      water vapor. The experiments further highlight the remarkable ability of hot CO32
      ions to behave as a base in reactions with protic and Lewis acids.

PMID- 21182319
TI  - A Stark future for quantum control.
AB  - We present an overview of developments using the nonresonant dynamic Stark effect
      within the fields of time-resolved molecular dynamics and quantum control,
      drawing on examples from our own recent work. Particular emphasis is placed on
      the notion that "dynamics" and "control" are not distinct disciplines and that a
      clear synergy exits between these areas which has, up to now, been somewhat
      underexploited. The dynamic Stark effect is a universal interaction which we
      expect to have broad applicability.

PMID- 21182320
TI  - Extending classical molecular theory with polarization.
AB  - A classical, polarizable, electrostatic theory of short-ranged atom-atom
      interactions, incorporating the smeared nature of atomic partial charges, is
      presented. Detailed models are constructed for CO monomer and for CO interacting
      with an iron atom, as a first step toward heme proteins. A good representation is
      obtained of the bond-length-dependent dipole of CO monomer from fitting at the
      equilibrium distance only. Essential features of the binding of CO to myoglobin
      (Mb) and model heme compounds, including the binding energy, the position of the
      minimum in the Fe-C potential, the Fe-C frequency, the bending energy, the linear
      geometry of FeCO, and the increase of the Stark tuning rate and IR intensity, are
      obtained, suggesting that a substantial part of the Fe-CO interaction consists of
      a classical, noncovalent, "electrostatic bond ". The binding energy is primarily
      polarization energy, and the polarization energy of an OH pair in water is shown
      to be comparable to the experimental hydrogen bond energy.

PMID- 21182321
TI  - Structural analysis of protein complexes with sodium alkyl sulfates by small
      angle scattering and polyacrylamide gel electrophoresis.
AB  - Small-angle X-ray (SAXS) and neutron (SANS) scattering is used to probe the
      structure of protein-surfactant complexes in solution and to correlate this
      information with their performance in gel electrophoresis. Proteins with sizes
      between 6.5 to 116 kDa are denatured with sodium alkyl sulfates (SC(x)S) of
      variable tail lengths. Several combinations of proteins and surfactants are
      analyzed to measure micelle radii, the distance between micelles, the extension
      of the complex, the radius of gyration, and the electrophoretic mobility. The
      structural characterization shows that most protein-surfactant complexes can be
      accurately described as pearl-necklace structures with spherical micelles.
      However, protein complexes with short surfactants (SC(8)S) bind with micelles
      that deviate significantly from spherical shape. Sodium decyl (SC(10)S) and
      dodecyl (SC(12)S, more commonly abbreviated as SDS) sulfates result in the best
      protein separations in standard gel electrophoresis. Particularly, SC(10)S shows
      higher resolutions for complexes of low molecular weight. The systematic
      characterization of alkyl sulfate surfactants demonstrates that changes in the
      chain architecture can significantly affect electrophoretic migration so that
      protein-surfactant structures could be optimized for high resolution protein
      separations.

PMID- 21182322
TI  - Bile-salt-induced aggregation of poly(N-isopropylacrylamide) and lowering of the
      lower critical solution temperature in aqueous solutions.
AB  - The effect of sodium cholate (NaC; concentration 1-16 mM), a biological
      surfactant, on the aggregation behavior of 1% (w/v, 2.2 * 10(-3) M) poly(N
      isopropylacrylamide) (PNIPAM) aqueous solutions was studied as a function of
      temperature. From turbidity, dynamic light scattering, viscosity, and
      fluorescence measurements, it was observed that (i) there is NaC-induced
      nanoscale aggregation of PNIPAM in its sol state and (ii) the lower critical
      solution temperature corresponding to sol-gel transition shifts to a lower
      temperature by about 2  degrees C.

PMID- 21182323
TI  - Supramolecular strategies to construct biocompatible and photoswitchable
      fluorescent assemblies.
AB  - We designed and synthesized an amphiphilic copolymer with pendant hydrophobic
      decyl and hydrophilic poly(ethylene glycol) chains along a common
      poly(methacrylate) backbone. This macromolecular construct captures hydrophobic
      boron dipyrromethene fluorophores and hydrophobic spiropyran photochromes and
      transfers mixtures of both components in aqueous environments. Within the
      resulting hydrophilic supramolecular assemblies, the spiropyran components retain
      their photochemical properties and switch reversibly to the corresponding
      merocyanine isomers upon ultraviolet illumination. Their photoinduced
      transformations activate intermolecular electron and energy transfer pathways,
      which culminate in the quenching of the boron dipyrromethene fluorescence. As a
      result, the emission intensity of these supramolecular constructs can be
      modulated in aqueous environments under optical control. Furthermore, the
      macromolecular envelope around the fluorescent and photochromic components can
      cross the membrane of Chinese hamster ovarian cells and transport its cargo
      unaffected into the cytosol. Indeed, the fluorescence of these supramolecular
      constructs can be modulated also intracellularly by operating the photochromic
      component with optical inputs. In addition, cytotoxicity tests demonstrate that
      these supramolecular assemblies and the illumination conditions required for
      their operation have essentially no influence on cell viability. Thus,
      supramolecular events can be invoked to construct fluorescent and photoswitchable
      systems from separate components, while imposing aqueous solubility and
      biocompatibility on the resulting assemblies. In principle, this simple protocol
      can evolve into a general strategy to deliver and operate intracellularly
      functional molecular components under optical control.

PMID- 21182324
TI  - Kinetics of reactions of the Actinomadura R39 DD-peptidase with specific
      substrates.
AB  - The Actinomadura R39 DD-peptidase catalyzes the hydrolysis and aminolysis of a
      number of small peptides and depsipeptides. Details of its substrate specificity
      and the nature of its in vivo substrate are not, however, well understood. This
      paper describes the interactions of the R39 enzyme with two peptidoglycan-mimetic
      substrates 3-(D-cysteinyl)propanoyl-D-alanyl-D-alanine and 3-(D
      cysteinyl)propanoyl-D-alanyl-D-thiolactate. A detailed study of the reactions of
      the former substrate, catalyzed by the enzyme, showed DD-carboxypeptidase, DD
      transpeptidase, and DD-endopeptidase activities. These results confirm the
      specificity of the enzyme for a free D-amino acid at the N-terminus of good
      substrates and indicated a preference for extended D-amino acid leaving groups.
      The latter was supported by determination of the structural specificity of amine
      nucleophiles for the acyl-enzyme generated by reaction of the enzyme with the
      thiolactate substrate. It was concluded that a specific substrate for this
      enzyme, and possibly the in vivo substrate, may consist of a partly cross-linked
      peptidoglycan polymer where a free side chain N-terminal un-cross-linked amino
      acid serves as the specific acyl group in an endopeptidase reaction. The enzyme
      is most likely a DD-endopeptidase in vivo. pH-rate profiles for reactions of the
      enzyme with peptides, the thiolactate named above, and beta-lactams indicated the
      presence of complex proton dissociation pathways with sticky substrates and/or
      protons. The local structure of the active site may differ significantly for
      reactions of peptides and beta-lactams. Solvent kinetic deuterium isotope effects
      indicate the presence of classical general acid/base catalysis in both acylation
      and deacylation; there is no evidence of the low fractionation factor active site
      hydrogen found previously in class A and C beta-lactamases.

PMID- 21182325
TI  - Synthesis, physicochemical characterization, and biological activities of new
      carnosine derivatives stable in human serum as potential neuroprotective agents.
AB  - The synthesis and the physicochemical and biological characterization of a series
      of carnosine amides bearing on the amido group alkyl substituents endowed with
      different lipophilicity are described. All synthesized products display carnosine
      like properties differentiating from the lead for their high serum stability.
      They are able to complex Cu(2+) ions at physiological pH with the same
      stoichiometry as carnosine. The newly synthesized compounds display highly
      significant copper ion sequestering ability and are capable of protecting LDL
      from oxidation catalyzed by Cu(2+) ions, the most active compounds being the most
      hydrophilic ones. All the synthesized amides show quite potent carnosine-like HNE
      quenching activity; in particular, 7d, the member of the series selected for this
      kind of study, is able to cross the blood-brain barrier (BBB) and to protect
      primary mouse hippocampal neurons against HNE-induced death. These products can
      be considered metabolically stable analogues of carnosine and are worthy of
      additional investigation as potential neuroprotective agents.

PMID- 21182326
TI  - Lattice distortion oriented angular self-assembly of monolayer titania sheets.
AB  - Self-assembly of exfoliated monolayer titania sheets is investigated by detailed
      transmission electron microscopy and the force field calculations. It is
      demonstrated for the first time that slight but significant lattice distortions
      result in modified angular self-assembly of exfoliated monolayer Ti(0.87)O(2)
      sheets. These findings significantly broaden current knowledge of the self
      assembly of exfoliated nanoscale layered sheets, which may render the potential
      manipulation of self-assembly of nanosheets.

PMID- 21182327
TI  - Interfacial engineering of organic nanofibril heterojunctions into highly
      photoconductive materials.
AB  - Photoconductive organic materials have gained increasing interest in various
      optoelectronics, such as sensors, photodetectors, and photovoltaics. However, the
      availability of such materials is very limited due to their intrinsic low charge
      carrier density and mobility. Here, we present a simple approach based on
      nanofibril heterojunction to achieve high photoconductivity with fast
      photoresponse, that is, interfacial engineering of electron donor (D) coating
      onto acceptor (A) nanofibers via optimization of hydrophobic interaction between
      long alkyl side-chains. Such nanofibril heterojunctions possess two prominent
      features that are critical for efficient photocurrent generation: the nanofibers
      both create a large D/A interface for increased charge separation and act as long
      range transport pathways for photogenerated charge carriers toward the
      electrodes, and the alkyl groups employed not only enable effective surface
      adsorption of D molecules on the nanofibers for effective electron-transfer
      communication, but also spatially separate the photogenerated charge carriers to
      prevent their recombination. The reported approach represents a simple, adaptable
      method that allows for the development and optimization of photoconductive
      organic materials.

PMID- 21182328
TI  - Thermally induced changes in amphiphilicity drive reversible restructuring of
      assemblies of ABC triblock copolymers with statistical polyether blocks.
AB  - ABC triblock copolymers in which a block with stimulus-dependent solvophilicity
      resides between solvophilic and solvophobic end blocks can undergo reversible
      transitions between different thermodynamically stable assemblies in the presence
      or absence of stimulus. As a new example of such a copolymer system,
      thermoresponsive poly(ethylene oxide)-b-poly(ethylene oxide-stat-butylene oxide)
      b-poly(isoprene) (E-BE-I) triblock copolymers with narrow molecular weight
      distributions (M(w)/M(n): 1.05-1.18) were prepared by sequential living anionic
      and nitroxide-mediated radical polymerizations. The specific copolymers examined
      (9.0 <= M(n) <= 14.4 kg/mol, 14% <= wt % isoprene <=35%) form near-spherical
      aggregates with narrow size distributions at 25  degrees C. The thermoresponsive
      behavior of these polymers was studied by applying cloud point, DLS, and TEM
      measurements to a representative polymer, E(2.3)BE(5.3)I(2.3). The transformation
      of polymer aggregates from spherical micelles to vesicles (polymersomes) at
      elevated temperatures was detected by DLS and TEM studies, both with and without
      cross-linking of polymer assemblies. The rate of transformation with E-BE-I
      systems is more rapid than that observed for poly(ethylene oxide)-b-poly(N
      isopropylacrylamide)-b-poly(isoprene) assemblies, suggesting that interchain
      hydrogen bonding of responsive blocks after dehydration plays an important role
      in the kinetics of aggregate rearrangement.

PMID- 21182330
TI  - Scaling the chirality in porphyrin J-nanoaggregates.

PMID- 21182331
TI  - Facile electrochemical synthesis of hexagonal Cu2O nanotube arrays and their
      application.
AB  - Large-scale and highly oriented single-crystalline hexagonal Cu(2)O nanotube
      arrays have been successfully synthesized using a two-step solution approach,
      which involves the electrodeposition of oriented Cu(2)O nanorods and a subsequent
      dissolution technique along the c axis to form a tubular structure. Herein,
      NH(4)Cl was found to be an effectual additive, and it can successfully realize
      the dissolution process of Cu(2)O from nanorods to nanotubes. The dissolution
      mechanism of Cu(2)O from nanorods to nanotubes was illustrated in detail. These
      prepared Cu(2)O nanotube arrays were characterized by SEM, EDS, XRD, XPS, and
      TEM. The photoluminescence (PL) spectrum of Cu(2)O nanotube arrays was also
      measured, and it shows there is a greater fraction of copper or oxygen vacancies
      in these prepared Cu(2)O nanotubes. Finally, the applications of Cu(2)O nanotube
      arrays for gas sensors were investigated in this paper.

PMID- 21182329
TI  - Metal-free sequential [3 + 2]-dipolar cycloadditions using cyclooctynes and 1,3
      dipoles of different reactivity.
AB  - Although metal-free cycloadditions of cyclooctynes and azides to give stable
      1,2,3-triazoles have found wide utility in chemical biology and material
      sciences, there is an urgent need for faster and more versatile bioorthogonal
      reactions. We have found that nitrile oxides and diazocarbonyl derivatives
      undergo facile 1,3-dipolar cycloadditions with cyclooctynes. Cycloadditions with
      diazocarbonyl derivatives exhibited similar kinetics as compared to azides,
      whereas the reaction rates of cycloadditions with nitrile oxides were much
      faster. Nitrile oxides could conveniently be prepared by direct oxidation of the
      corresponding oximes with BAIB, and these conditions made it possible to perform
      oxime formation, oxidation, and cycloaddition as a one-pot procedure. The
      methodology was employed to functionalize the anomeric center of carbohydrates
      with various tags. Furthermore, oximes and azides provide an orthogonal pair of
      functional groups for sequential metal-free click reactions, and this feature
      makes it possible to multifunctionalize biomolecules and materials by a simple
      synthetic procedure that does not require toxic metal catalysts.

PMID- 21182332
TI  - Molecular simulation of the pressure-induced crystallographic phase transition of
      p-terphenyl.
AB  - The pressure- and temperature-induced polymorphic crystal phase transitions of p
      terphenyl (PTP) have been modeled using a modified PCFF interaction force field.
      Modifications of the interaction potential were necessary to simultaneously model
      both the temperature-induced phase transition at ambient pressure and the
      pressure-induced phase transition at low temperature. Although the high
      temperature and high-pressure phases are both characterized by flattening of the
      PTP molecule, the mechanisms of the temperature- and pressure-induced phase
      transitions are different. At high temperature thermal energy exceeds the
      torsional barrier, resulting in a bimodal phenyl ring twist angle distribution
      that averages to zero. In contrast, compression of PTP at high pressure results
      in a static planar structure. At high pressure the compression of the unit cell
      is also characterized by large compression of the a lattice parameter and weak
      compression of c, but some expansion of the b lattice parameter. The expansion of
      the b lattice parameter is likely associated with pressure-induced soft mode
      behavior of some lattice vibrations as well as soft mode behavior of pseudolocal
      phonons associated with impurities in PTP. The crystallographic angles alpha,
      beta, and gamma also indicate a triclinic crystal phase above the critical phase
      transition pressure of P(c) ~ 0.5 GPa at low temperature, suggesting a distinct
      phase separate from the monoclinic high-pressure phase at high temperature.

PMID- 21182333
TI  - Synthesis of polysubstituted olefins by Pd-catalyzed cross-coupling reaction of
      tosylhydrazones and aryl nonaflates.
AB  - Aryl nonaflates are employed as electrophiles in the Pd-catalyzed cross-coupling
      with tosylhydrazones affording di-, tri-, and tetrasubstituted olefins. Fine
      tunning of the reaction conditions are required to accomplish the coupling
      successfully, including the addition of LiCl and the presence of small amounts of
      water. Under the optimized conditions, the reactions proceed with high yield and
      also high stereoselectivity depending on the nature of the coupling partners.

PMID- 21182334
TI  - Palladium-catalyzed cross-coupling of indium homoenolate with aryl halide with
      wide functional group compatibility.
AB  - An efficient palladium-catalyzed cross-coupling of indium homoenolate with aryl
      halide is described. The reactions proceeded efficiently in DMA at 100  degrees C
      to afford the desired products of beta-aryl ketones in moderate to good yields.
      Various important functional groups including COR, COOR, CHO, CN, OH, and NO(2)
      can be well tolerated in the protocol.

PMID- 21182335
TI  - Copper-catalyzed oxidative amination of benzoxazoles via C-H and C-N bond
      activation: a new strategy for using tertiary amines as nitrogen group sources.
AB  - An efficient and conceptually new method for oxidative amination of azoles with
      tertiary amines via copper-catalyzed C-H and C-N bond activation has been
      developed. This protocol can be performed in the absence of external base and
      only requires atmospheric oxygen as oxidant. The catalyst system is very simple
      and efficient, which opens a new way for using tertiary amines as nitrogen group
      sources for C-N bond formation reactions.

PMID- 21182336
TI  - Fluoroalcohol-induced modulation of the pathway of amyloid protofibril formation
      by barstar.
AB  - To understand how the conformational heterogeneity of protofibrils formed by any
      protein, as well as the mechanisms of their formation, are modulated by a change
      in aggregation conditions, we studied the formation of amyloid protofibrils by
      barstar at low pH by multiple structural probes in the presence of
      hexafluoroisopropanol (HFIP). In the presence of 10% HFIP, aggregation proceeds
      with the transient formation of spherical oligomers and leads to the formation of
      both protofibrils and fibrils. Curly short protofibrils and fibrils are seen to
      form early during the aggregation reaction, and both are seen to grow gradually
      in length during the course of the reaction. Atomic force microscopy images
      reveal that the HFIP-induced protofibrils are long (~300 nm in length), curly,
      and beaded and appear to be composed primarily of beta-sheet bilayers, with
      heights of ~2.4 nm. The protofibrils formed in the presence of HFIP differ in
      both their structures and their stabilities from the protofibrils formed either
      in the absence of alcohol or in the presence of a related alcohol,
      trifluoroethanol (TFE). Aggregation appears to proceed via an isodesmic
      polymerization mechanism. Internal structure in the growing aggregates changes in
      two stages during protofibril formation. In the first stage, an alpha-helix-rich
      oligomeric intermediate is formed. In the second stage, the level of beta-sheet
      structure increases at the expense of some alpha-helical structure. The second
      stage itself appears to occur in two distinct steps. The creation of thioflavin T
      binding sites occurs concomitantly with aggregate elongation and is seen to
      precede the change in secondary structure. The long straight fibrils with
      characteristic heights of 8-10 nm, which form in the course of the HFIP-induced
      aggregation reaction, have not been observed to form either in the absence of
      alcohol or in the presence of TFE.

PMID- 21182337
TI  - Interaction of selenoprotein W with 14-3-3 proteins: a computational approach.
AB  - SelW, a protein containing a selenocysteine (Sec) in a conserved Cys-X-X-Sec
      motif, has been suggested to have an antioxidant role in cell metabolism. SelW is
      known to specifically interact with different isoforms of 14-3-3 proteins. The
      latter are involved in several cellular processes such as regulation of the cell
      cycle, metabolism control, apoptosis, protein trafficking, and gene
      transcription. 14-3-3 proteins feature a conserved solvent-exposed cysteine
      residue, in a surface environment prone to induce chemical modifications of the
      thiol functionality following oxidative stress. The structures of 12 homologous
      complexes between SelW and 14-3-3 were calculated using sequential alignments,
      molecular modeling, and docking algorithms guided by known experimental NMR data.
      These structures reveal the viability of a protein complex in which the conserved
      Sec residue on SelW approaches the conserved exposed Cys on 14-3-3, making a
      plausible Sec-Se-S-Cys bond. On the basis of the structural information derived
      from these calculations, we propose a working hypothesis that entails a role for
      SelW as a physiological partner of 14-3-3 proteins, able to facilitate a redox
      based regulation mechanism.

PMID- 21182340
TI  - A review of economic evaluations of darunavir boosted by low-dose ritonavir in
      treatment-experienced persons living with HIV infection.
AB  - Darunavir boosted by low-dose ritonavir (DRV/r), at a daily dose of 600/100 mg
      twice a day (bid), has been shown to be superior to alternative highly active
      antiretroviral therapy (HAART) regimens for the management of treatment
      experienced, HIV-infected adults in the phase IIb POWER trials and the phase III
      TITAN trial. Economic analyses of different types that have been performed for
      several countries to investigate the cost effectiveness and budgetary impact of
      DRV/r 600/100 mg bid for treatment-experienced people living with HIV (PLHIV)
      based on the clinical data gathered in the POWER and TITAN trials are reviewed
      for consistency and their value to different decision-makers is assessed. Cost
      utility analyses for the USA and several European countries indicate that DRV/r
      based HAART is cost effective compared with other standard of care protease
      inhibitor (PI)-based regimens in PLHIV with evidence of PI resistance. For all of
      these countries, the estimated cost-utility ratio is well below typical benchmark
      values and these ratios are robust, as demonstrated by one-way sensitivity and
      variability analyses and multi-way probabilistic sensitivity analyses. Studies
      using other metrics including the average 1-year drug cost per patient with a
      plasma HIV-RNA level less than 50 copies/mL at 48 weeks, the incremental drug
      cost per additional patient with a plasma HIV-RNA level less than 50 copies/mL at
      48 weeks, the total (antiretroviral and non-antiretroviral) costs during the
      first year of treatment, and the total healthcare budget impact during the first
      5 years of treatment provided further evidence of the positive economic outcomes
      with the use of DRV/r in treatment-experienced PLHIV. Different measures of
      economic outcomes are useful for different types of decision-makers and different
      types of decisions. In general, the results of these different types of analyses
      will be consistent with each other. For darunavir, the economic analyses reviewed
      in this paper demonstrate that the use of DRV/r 600/100 mg bid in the management
      of HIV-infected, treatment-experienced adults who have failed at least one of the
      other currently available PIs is cost effective and may be cost saving.

PMID- 21182341
TI  - Clinical management of treatment-experienced, HIV/AIDS patients in the
      combination antiretroviral therapy era.
AB  - Despite the success of combination antiretroviral therapy (ART) in improving
      clinical outcomes, treatment failure remains a significant challenge,
      particularly for highly treatment-experienced patients. This review evaluates
      current issues in the management of HIV-infected, treatment-experienced patients.
      It may provide guidance in selecting active, tolerable drug combinations that
      promote a reasonable quality of life, full adherence and a durable treatment
      response. Current treatment guidelines and clinical trial data were reviewed to
      identify reasons for treatment failure and to summarize therapy options for
      treatment-experienced and highly treatment-experienced patients. Current
      treatment options include nucleoside reverse transcriptase inhibitors (NRTIs) and
      non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors
      (PIs), and inhibitors of viral fusion, entry and integration. The use of NRTIs
      may be limited by resistance and short- and long-term toxicities. Resistance has
      restricted the NNRTI class with cross-resistance preventing their sequential use.
      Etravirine, a next-generation NNRTI, however, demonstrates effective virological
      suppression in patients with baseline NNRTI resistance. Boosted PIs are key
      components of ART for treatment-experienced patients. The newer boosted PIs
      tipranavir and darunavir have demonstrated impressive activity in patients with
      resistance to NRTIs, NNRTIs and PIs, as well as in less treatment-experienced
      patients for darunavir. The fusion inhibitor enfuvirtide has demonstrated
      efficacy in heavily treatment-experienced patients, although injection-site
      reactions can be problematical. The recently approved integrase inhibitor
      raltegravir has also shown impressive potency and tolerability in highly
      treatment-experienced patients. Finally, the entry inhibitor maraviroc has also
      been approved recently, although its use is somewhat limited by the need for HIV
      tropism testing. The availability of potent next-generation PIs, NNRTIs,
      integrase and entry-inhibitors may offer improved therapy for treatment
      experienced patients, including those with multiresistant virus. These new drugs
      may reduce HIV immunological and clinical progression and in doing so may also
      reduce treatment costs.

PMID- 21182342
TI  - The impact of disease stage on direct medical costs of HIV management: a review
      of the international literature.
AB  - The global prevalence of HIV infection continues to grow, as a result of
      increasing incidence in some countries and improved survival where highly active
      antiretroviral therapy (HAART) is available. Growing healthcare expenditure and
      shifts in the types of medical resources used have created a greater need for
      accurate information on the costs of treatment. The objectives of this review
      were to compare published estimates of direct medical costs for treating HIV and
      to determine the impact of disease stage on such costs, based on CD4 cell count
      and plasma viral load. A literature review was conducted to identify studies
      meeting prespecified criteria for information content, including an original
      estimate of the direct medical costs of treating an HIV-infected individual,
      stratified based on markers of disease progression. Three unpublished cost-of
      care studies were also included, which were applied in the economic analyses
      published in this supplement. A two-step procedure was used to convert costs into
      a common price year (2004) using country-specific health expenditure inflators
      and, to account for differences in currency, using health-specific purchasing
      power parities to express all cost estimates in US dollars. In all nine studies
      meeting the eligibility criteria, infected individuals were followed
      longitudinally and a 'bottom-up' approach was used to estimate costs. The same
      patterns were observed in all studies: the lowest CD4 categories had the highest
      cost; there was a sharp decrease in costs as CD4 cell counts rose towards 100
      cells/mm3; and there was a more gradual decline in costs as CD4 cell counts rose
      above 100 cells/mm3. In the single study reporting cost according to viral load,
      it was shown that higher plasma viral load level (> 100,000 HIV-RNA copies/mL)
      was associated with higher costs of care. The results demonstrate that the cost
      of treating HIV disease increases with disease progression, particularly at CD4
      cell counts below 100 cells/mm3. The suggestion that costs increase as the plasma
      viral load rises needs independent verification. This review of the literature
      further suggests that publicly available information on the cost of HAART by
      disease stage is inadequate. To address the information gap, multiple
      stakeholders (governments, pharmaceutical industry, private insurers and non
      governmental organizations) have begun to establish and support an independent,
      high quality and standardized multicountry data collection for evaluating the
      cost of HIV management. An accurate, representative and relevant cost-estimate
      data resource would provide a valuable asset to healthcare planners that may lead
      to improved policy and decision-making in managing the HIV epidemic.

PMID- 21182343
TI  - Medical resource utilization and cost of HIV-related care in the highly active
      antiretroviral therapy era at a University Clinic in Sweden.
AB  - INTRODUCTION: Little is known regarding healthcare costs for HIV/AIDS patients in
      the era of highly active antiretroviral therapy (HAART) and subgroups of patients
      according to the severity and progression of HIV infection in Sweden. The
      objective of this study is therefore to describe the direct medical resource use
      and cost of healthcare for HIV patients at a university clinic in Sweden.
      METHODS: A patient registry database for HIV treatment at the Department of
      Infectious Diseases, Sahlgrenska University Hospital, between 2000 and 2005
      provided information on patient characteristics, antiretroviral drugs and
      dosages, tests and diagnostic procedures, outpatient visits and inpatient stays.
      The review used publicly available unit costs with a county council perspective,
      expressed in 2006 Euros. RESULTS: Two hundred and eighty-five patients with a
      mean age of 38 years in 2000 (64% men) were followed for 1368 patient-years. They
      had a mean (median) of 6.3 (0) inpatient days, 4.1 (3.7) physician visits, 4.2
      (3.8) nurse visits, 2.6 (0.7) counsellor visits and 11.5 (7.7) tests and
      diagnostic procedures per patient-year. Only 12 deaths were recorded during the
      study period, and the proportion of treated patients with successful treatment
      (HIV-RNA < 50 copies/mL) increased from 74% to 92% during the period. The mean
      cost per patient-month amounted to ?1069. The main cost driver was HIV drugs
      (51%), followed by inpatient stays (including hospitalizations for opportunistic
      infections; 22%), outpatient physician, nurse or therapist visits (19%) and
      diagnostics and tests (7%). All non-drug costs increased with a decreasing CD4
      cell count. CONCLUSIONS: Overall, approximately half of the direct costs of HIV
      treatment were not related to antiretroviral treatment. The non-antiretroviral
      costs were inversely correlated with HIV-induced immune deficiency.

PMID- 21182344
TI  - The cost of managing HIV infection in highly treatment-experienced, HIV-infected
      adults in France.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) has greatly enhanced HIV
      management, lowering the risk of clinical disease progression and death by
      substantially improving HIV-induced immune deficiency. Lower CD4 cell counts have
      consistently been associated with higher direct costs of HIV patient care. The
      aim of this study was to analyze HIV costs of care in France at different levels
      of HIV-induced immune deficiency (as measured by the CD4 cell count) using recent
      data from treatment-experienced patients. METHODS: This analysis used data from
      the French Hospital Database in HIV, containing data on approximately 50% of the
      French HIV population. Patients were included in the analysis if they had visited
      a participating centre from 2003 to 2005, had CD4 cell counts determined at least
      twice during the study period, and had been prescribed at least two nucleoside
      reverse transcriptase inhibitors, one non-nucleoside reverse transcriptase
      inhibitor and two protease inhibitors since their first consultation. Resources
      consumed were counted and aggregated according to the CD4 cell count level.
      Standard costs were applied. RESULTS: Periods with the lowest CD4 cell counts
      were associated with increased prescription rates of antiviral agents (other than
      anti-HIV agents), antiparasitic drugs and antimycobacterial agents.
      Antiretroviral treatments accounted for 80% of all medications prescribed during
      the study period. Hospitalization rates decreased with increasing CD4 cell
      counts, with 0.72 hospitalizations per patient-year for those with CD4 cell
      counts of 50 cells/mm3 or less compared with 0.05 per patient-year for patients
      with CD4 cell counts greater than 500 cells/mm3. There was a clear trend towards
      lower mean healthcare costs per patient-year with decreasing immune deficiency;
      from ?34,286 to ?12,361. CONCLUSIONS: Our study showed an association between the
      degree of HIV-induced immune deficiency (measured by CD4 cell count) and the
      costs of managing HIV infection among highly pre-treated, HIV-infected
      individuals in France in the HAART era.

PMID- 21182345
TI  - Costs to achieve undetectable HIV RNA with darunavir-containing highly active
      antiretroviral therapy in highly pretreated patients: the POWER experience.
AB  - BACKGROUND: Very few studies have evaluated the cost of highly active
      antiretroviral therapy (HAART) per successful treatment in HIV-infected patients.
      OBJECTIVES: To evaluate the cost of achieving undetectable plasma HIV-RNA levels
      in highly treatment-experienced, HIV-1-infected adults receiving
      darunavir/ritonavir (DRV/r 600 mg/100 mg twice a day) or control protease
      inhibitor (PI)-based HAART. METHODS: The mean annual per-patient cost of DRV/r
      and control PI-based HAART was determined from the proportional use of
      antiretroviral agents in the DRV/r and control PI arms of the pooled POWER 1 and
      2 trials, applying drug acquisition costs for 13 healthcare settings. The mean
      annual cost per patient of achieving undetectable plasma HIV-RNA levels (<50
      copies/mL) was calculated by dividing the cost of each treatment by the
      proportion of patients with undetectable plasma HIV-RNA levels after 48 weeks in
      the DRV/r (45%) and control PI (10%) arms of the POWER trials. RESULTS: Whereas
      absolute costs of treatment were 1-19% higher with DRV/r versus control PI-based
      HAART depending on the healthcare setting, the mean annual per-patient cost of
      achieving undetectable plasma HIV-RNA levels was 73-78% lower. These cost savings
      were maintained in the sensitivity analyses, adjusting for control PI and
      enfuvirtide use, and the number of active drugs in the background regimen. The
      incremental annual cost per additional patient achieving undetectable plasma HIV
      RNA levels with DRV/r versus control PI-based HAART in POWER 1 and 2 (L4148)
      compared favourably with that determined for enfuvirtide (L137, 740; TORO trials)
      and tipranavir/ritonavir (L32,176; RESIST) versus control therapy. CONCLUSIONS:
      DRV/r-based HAART provided consistent reductions in the cost of achieving
      undetectable plasma HIV-RNA levels compared with control PI-based therapy in
      highly treatment-experienced patients across various healthcare settings. The
      incremental cost per additional patient achieving undetectable plasma HIV-RNA
      levels with DRV/r versus control PI-based HAART was also lower than that
      calculated for other treatment options in this population. These results suggest
      that DRV/r is an economically viable option for highly treatment-experienced
      patients.

PMID- 21182346
TI  - Cost effectiveness of darunavir/ritonavir in highly treatment-experienced, HIV-1
      infected adults in the USA.
AB  - INTRODUCTION: Darunavir is a new protease inhibitor (PI) that is co-administered
      with low-dose ritonavir and has demonstrated substantial efficacy in clinical
      trials of highly treatment-experienced patients when combined with an optimized
      background regimen (with or without enfuvirtide). This study estimates the cost
      effectiveness of darunavir with ritonavir (DRV/r) in this population over 5-year
      and lifetime time horizons in the USA. METHODS: A Markov model was used to follow
      a treatment-experienced HIV-1 cohort through six health states, based on CD4 cell
      count: greater than 500, 351-500, 201-350, 101-200, 51-100 and 0-50 cells/mm3,
      and death. The magnitude of the CD4 cell count increase and duration of
      increasing and stable periods were derived from week 48 DRV/r clinical trial
      results (POWER 1 and 2). The treatment pathway assumed one regimen switch
      following treatment failure on the initial regimen. The use of antiretroviral
      drugs was based on usage in DRV/r clinical trials. US daily wholesale acquisition
      costs were calculated using the recommended daily doses. For each CD4 cell count
      range, utility values, HIV-1-related mortality rates and costs for medical
      resources (other than antiretroviral drug costs) were obtained from published
      literature. Non-HIV-1-related mortality rates were calculated by applying a
      relative risk value to the US general population age and gender-specific
      mortality rates. Costs and outcomes were discounted at 3% per year. One-way and
      probabilistic sensitivity analyses and variability analysis were performed.
      RESULTS: In a 5-year analysis, patients receiving DRV/r experienced 3.80 quality
      adjusted life-years (QALYs) and incurred total medical costs of US$217,288, while
      those receiving control PIs experienced 3.60 QALYs and incurred costs of
      US$218,962. DRV/r was both more effective and less costly than control PIs. For
      the lifetime analysis, the QALYs and lifetime medical costs with DRV/r were 10.03
      and US$565,358, compared with 8.76 and US$527,287 with control PIs. The
      incremental cost-effectiveness ratio for DRV/r compared with control PIs was
      US$30,046. One-way sensitivity analyses for both time horizons indicated that the
      results were most sensitive to changes in the rate of CD4 cell count change
      during stable and declining periods (lifetime only), duration of stable period (5
      year only) and HIV-1-related mortality rates. The results of the variability
      analysis were most sensitive to the model time horizon. Nevertheless, for all
      ranges and scenarios tested in these analyses, the incremental cost per QALY
      gained remained below US$50,000. The probabilistic sensitivity analysis showed
      that there was a 0.921 and 0.950 probability of a cost-effectiveness ratio below
      US$50,000 per QALY for the 5-year and lifetime time horizon, respectively.
      CONCLUSIONS: DRV/r is predicted to be cost effective compared with control PI in
      highly treatment-experienced patients and is predicted to yield an average of
      0.20 additional QALYs per treatment-experienced patient over 5 years and 1.27
      additional QALYs over a lifetime in this population.

PMID- 21182347
TI  - Cost effectiveness of darunavir/ritonavir 600/100 mg bid in protease inhibitor
      experienced, HIV-1-infected adults in Belgium, Italy, Sweden and the UK.
AB  - BACKGROUND: Two phase II trials (POWER 1 and 2) have demonstrated that darunavir
      co-administered with low-dose ritonavir (DRV/r) provides significant clinical
      benefit compared with control protease inhibitors (PIs) in highly treatment
      experienced, HIV-1-infected adults, when co-administered with optimized
      background therapy (OBR). OBJECTIVE: To determine whether DRV/r is cost effective
      compared with control PIs, from the perspective of Belgian, Italian, Swedish and
      UK reimbursement authorities, when used in treatment-experienced patients similar
      to those included in the POWER 1 and 2 trials. METHODS: An existing Markov model
      containing health states defined by CD4 cell count ranges (> 500, 351-500, 201
      350, 101-200, 51-100 and 0-50 cells/mm3) and death was adapted for use in four
      European healthcare settings. Baseline demographics, CD4 cell count distribution
      and antiretroviral drug usage reflected those reported in the POWER 1 and 2
      trials. Virological/immunological response rates and matching transition
      probabilities over the patient's lifetime were based on results from the POWER
      trials and published data. After treatment failure, patients were assumed to
      switch to a tipranavir-containing regimen plus OBR. For each CD4 cell count
      range, utility values and HIV-related mortality rates were obtained from the
      published literature. National all-cause mortality data and published data on the
      increased risk of non HIV-related mortality in HIV-infected individuals were
      taken into account in the model. Data from observational studies conducted in
      each healthcare setting were used to determine resource-use patterns and costs
      associated with each CD4 cell count range. Unit costs were derived from official
      local sources; a lifetime horizon was taken and discount rates were selected
      based on local guidelines. RESULTS: In the base-case analysis, quality-adjusted
      life-year (QALY) gains of up to 1.397 in Belgium, over 1.171 in Italy, 1.142 in
      Sweden and 1.091 in the UK were predicted when DRV/r-based therapy was used
      instead of control PI-based treatment. The base-case analyses predicted an
      incremental cost-effectiveness ratio (ICER) of ?11,438/QALY in Belgium,
      ?12,122/QALY in Italy,?10,942/QALY in Sweden and ?16,438/QALY in the UK. Assuming
      an acceptability threshold of ?30,000/QALY, DRV/r-based therapy remained cost
      effective over all parameter ranges tested in extensive one-way sensitivity
      analyses. Probabilistic sensitivity analysis revealed a 95% (Belgium), 97%
      (Italy), 92% (Sweden) or 78% (UK) probability of attaining an ICER below this
      threshold. CONCLUSION: From four European payer perspectives, DRV/r-based
      antiretroviral therapy is predicted to be cost effective compared with currently
      available control PIs, when both are used with an OBR in treatment-experienced,
      HIV-1-infected adults who failed to respond to more than one PI-containing
      regimen.

PMID- 21182348
TI  - US cost effectiveness of darunavir/ritonavir 600/100 mg bid in treatment
      experienced, HIV-infected adults with evidence of protease inhibitor resistance
      included in the TITAN Trial.
AB  - INTRODUCTION: The phase III TITAN trial evaluated the use of darunavir with low
      dose ritonavir (DRV/r) 600/100 mg twice daily (bid) compared with lopinavir with
      low-dose ritonavir (LPV/r) in treatment-experienced, lopinavir-naive patients.
      This study estimates the cost effectiveness of DRV/r from a US societal
      perspective when compared with LPV/r in treatment-experienced patients with a
      profile similar to those TITAN patients who had one or more International AIDS
      Society - USA (IAS-USA) primary protease inhibitor (PI) resistance-associated
      mutations (RAMs) at baseline. This population had less advanced HIV disease and a
      broader range of previous PI exposure/failure (0 - >= 2 PIs) at enrollment than
      those in the darunavir phase IIb POWER trials. METHODS: An existing Markov model
      containing six health states defined by CD4 cell count range (>500, 351-500, 201
      350, 101-200, 51-100 and 0-50 cells/mm3) and an absorbing state of death was
      adapted. Baseline demographics, CD4 cell count distribution and antiretroviral
      drug usage, virological response (at week 24), and immunological response
      estimates and matching transition probabilities were based on data collected
      directly from the one or more IAS-USA PI mutation subpopulation during the first
      48 weeks of the TITAN trial, as well as from published literature. Patients were
      assumed to switch to a regimen containing tipranavir plus an optimized background
      regimen after treatment failure. For each CD4 cell count range or health state,
      the utility values, HIV and non-HIV-related mortality rates, and non
      antiretroviral-related cost of HIV care estimates were derived from published
      literature. Unit costs were derived from official local sources. A lifetime
      horizon was taken in the base-case analysis. RESULTS: The base-case analysis
      predicted discounted quality-adjusted survival gains of 0.493 quality-adjusted
      life-years (QALYs) for DRV/r compared with LPV/r, resulting in an incremental
      cost-effectiveness ratio (ICER) of US$23,057 per QALY gained over a lifetime
      horizon. Probabilistic sensitivity analysis indicated a 0.754 probability of an
      ICER below the threshold of US$50,000 per QALY gained. DRV/r remained cost
      effective over all parameter ranges tested in extensive one-way sensitivity
      analyses and variability analyses, which examined the impact of input parameter
      uncertainty and changes in model assumptions and treatment patterns,
      respectively. Shortening the model time horizon had the largest impact on the
      ICER, reducing it most notably to US$4919 with a 10-year time horizon.
      CONCLUSION: From a US societal perspective and based on an analysis of the
      patients with primary IAS-USA PI RAMs enrolled in the darunavir phase III TITAN
      trial, a highly active antiretroviral therapy (HAART) regimen containing DRV/r
      600/100 mg bid is estimated to be a cost-effective therapy when compared with a
      HAART regimen containing LPV/r, for the management of treatment-experienced, PI
      resistant, HIV-infected adults with a broad range of previous PI use/failure.

PMID- 21182349
TI  - Cost effectiveness of darunavir/ritonavir 600/100 mg bid in treatment
      experienced, lopinavir-naive, protease inhibitor-resistant, HIV-infected adults
      in Belgium, Italy, Sweden and the UK.
AB  - BACKGROUND: Using data from the phase IIb POWER trials, darunavir boosted with
      low-dose ritonavir (DRV/r; 600/100 mg twice daily; bid)-based highly active
      antiretroviral therapy (HAART) was shown to be significantly more efficacious and
      cost effective than other protease inhibitor (PI)-based therapy in highly
      treatment-experienced, HIV-1-infected adults. Furthermore, in the phase III TITAN
      trial (TMC114-C214), DRV/r 600/100 mg bid-based HAART generated a superior 48
      week virological response rate compared with standard-of-care lopinavir/ritonavir
      (LPV/r; 400/100 mg bid)-based therapy in treatment-experienced, lopinavir-naive
      patients, and in particular those with one or more International AIDS Society -
      USA (IAS-USA) primary PI resistance-associated mutations at baseline. These
      patients had a broader degree of previous PI use/failure (0 - >= 2) than the
      POWER patients. OBJECTIVES: To determine whether DRV/r 600/100 mg bid-based HAART
      is cost effective compared with LPV/r-based therapy, from the perspective of
      Belgian, Italian, Swedish and UK reimbursement authorities, when used in
      treatment-experienced patients similar to TITAN patients with one or more IAS-USA
      primary PI mutations at baseline. METHODS: An existing Markov model containing
      health states defined by CD4 cell count ranges (>500, 351-500, 201-350, 101-200,
      51-100 and 0-50 cells/mm3) and an absorbing state of death was adapted for use in
      the above-mentioned healthcare settings. Baseline demographics, CD4 cell count
      distribution, antiretroviral drug usage, virological/immunological response rates
      and matching transition probabilities were based on data collected during the
      first 48 weeks of therapy in the modelled subgroup of TITAN patients and the
      published literature. After treatment failure, patients were assumed to switch to
      a follow-on combination regimen. For each health state, utility values and
      mortality rates were obtained from the published literature. Data from local
      observational studies (Belgium, Sweden and Italy) or the published literature
      (UK) were used to determine resource-use patterns and costs associated with each
      CD4 cell count range. Unit costs were derived from official local sources; a
      lifetime horizon was taken and discount rates were chosen based on local
      guidelines. RESULTS: The base-case analysis predicted quality-adjusted life year
      (QALY) gains of 0.785 in Belgium, 0.608 in Italy, 0.584 in Sweden and 0.550 in
      the UK when DRV/r-based therapy was used instead of LPV/r-based treatment. The
      estimated base-case incremental cost-effectiveness ratios (ICERs) were ?6964/QALY
      gained in Belgium, ?9277/QALY gained in Italy, ?6868 (SEK69,687)/QALY gained in
      Sweden and ?14,778 (L12 612)/QALY gained in the UK. Assuming a threshold of
      ?30,000/QALY gained, DRV/r-based therapy remained cost effective over most
      parameter ranges tested in extensive one-way sensitivity analyses. The variation
      of immunological response rates and the time horizon were identified as important
      drivers of cost effectiveness. Probabilistic sensitivity analysis revealed a
      greater than 70% probability of achieving an ICER below this threshold in all
      four healthcare settings. CONCLUSION: From the perspective of Belgian, Italian,
      Swedish and UK payers, DRV/r 600/100 mg bid-based HAART is predicted to be cost
      effective compared with LPV/r 400/100 mg bid-based therapy, when used to manage
      treatment experienced, lopinavir-naive, PI-resistant, HIV-infected adults with a
      broad range of previous PI use/failure.

PMID- 21182350
TI  - Predicting direct costs of HIV care during the first year of darunavir-based
      highly active antiretroviral therapy using CD4 cell counts: evidence from POWER.
AB  - BACKGROUND: Given the association between CD4 cell counts and HIV-related
      morbidity/mortality, new antiretroviral therapies could potentially lower the
      direct costs of HIV care by raising CD4 cell counts. OBJECTIVES: To predict the
      effects of the ritonavir-boosted, HIV protease inhibitor (PI) darunavir on the
      direct costs of care, while accounting for CD4 cell counts, during the first year
      of therapy in highly treatment-experienced, HIV-infected adults in different
      healthcare settings. METHODS: The mean annual per-patient cost of
      darunavir/ritonavir (DRV/r) and control PI-based highly active antiretroviral
      therapy (HAART) was calculated from the proportional use of antiretroviral agents
      in the DRV/r and control PI arms of the pooled POWER 1 and 2 trials, applying
      drug-acquisition costs for five healthcare settings. Non-antiretroviral-related
      costs by CD4 cell count, derived from non-interventional studies in the same
      settings, were applied to the POWER data (proportion of patients with CD4 cell
      counts in different strata at week 48) to estimate mean annual non-antiretroviral
      related costs per patient in patients receiving DRV/r or control PI-based HAART
      during year 1. RESULTS: Across all settings, the mean annual per-patient cost of
      DRV/r-based treatment was 2-19% higher than that of control PI-based therapy
      during the first year of therapy. By raising CD4 cell counts, however, DRV/r
      based regimens were predicted to lower mean annual non-antiretroviral-related
      costs by 16-38% compared with control PI-based therapy. When combined, the total
      annual per-patient cost of HIV care during the first year of therapy was
      estimated to be 7% lower in the DRV/r compared with the control PI arm using US
      data, 8% lower using Swedish data, budget neutral using UK and Belgian data and
      5% higher using Italian data. CONCLUSIONS: Darunavir-based HAART may lower non
      antiretroviral-related costs compared with control PI-based therapy in highly
      treatment-experienced, HIV-infected patients during the first year of therapy by
      improving patients' CD4 cell counts. These costs could partly/fully offset the
      increased acquisition cost of DRV/r in this patient population over the same
      period.

PMID- 21182351
TI  - Modelling the budget impact of darunavir in the treatment of highly treatment
      experienced, HIV-infected adults in France.
AB  - BACKGROUND: A key element for payers in the assessment of the economic profile of
      a medication is its anticipated impact on the evolution of healthcare budgets.
      OBJECTIVES: To forecast the impact of the use of darunavir with low-dose
      ritonavir 600/100 mg twice a day (bid) in highly treatment-experienced, HIV
      infected adults who have failed one or more protease inhibitor (PI)-containing
      regimen on the budget of the French Sickness Fund (French healthcare system) over
      a 3-year time horizon. METHODS: A transition state model based on disease
      severity was developed that compared the evolution of antiretroviral and non
      antiretroviral-related direct costs of care in the target population over 3 years
      (2007-2009) under two scenarios: (1) darunavir enters the French market in year
      1; (2) darunavir is not available to the target population during 2007-2009.
      Model inputs were derived from a targeted analysis of the French hospital
      database in HIV, the darunavir POWER 1 and 2 trials and other relevant clinical
      studies. RESULTS: In the scenario where darunavir was available from year 1, the
      proportion of patients in the lower, more costly CD4 cell count strata (<= 100
      cells per mm3) was consistently lower than in the scenario without darunavir in
      each year of the model (17.0% vs 19.2%, 13.9% vs 18.3% and 10.8% vs 16.8% for
      years 1, 2 and 3, respectively). As a result, over the entire 3-year period, the
      net increase of antiretroviral drug costs (+ 5.6 million Euros; ?), resulting
      from the substitution of older, cheaper PIs by darunavir, is expected to be fully
      compensated by savings in hospitalization costs (?-9.7 million) and expenditures
      for other HIV-related (non-antiretroviral) medications (?-7.3 million), leading
      to a net saving of ?11.4 million or 2.9% of the total budget in the scenario
      without darunavir. Various sensitivity analyses confirmed these projected
      savings. CONCLUSION: The use of darunavir/ritonavir (DRV/r) 600/100 mg bid, in
      combination with other antiretroviral agents, in highly pre-treated, HIV-infected
      adults who have failed one or more PI-containing highly active antiretroviral
      therapy regimen is not expected to increase the budget of the French healthcare
      system, in comparison with a scenario without darunavir. Further research is
      needed to estimate the budget impact of the use of DRV/r in less treatment
      experienced, HIV-infected individuals in France.

PMID- 21182353
TI  - Payment for clinical pharmacy services revisited.

PMID- 21182354
TI  - Biostatistical applications in epidemiology.
AB  - Understanding the application of statistical methods is an essential component in
      the process of evaluating the medical literature. Statistical methods can differ
      when evaluating randomized controlled clinical trials (experimental design)
      compared with observational study designs such as cohort or case-control. A
      review of common statistical concepts includes variables, measures of central
      tendency, and measures of dispersion. Other methods include sensitivity,
      specificity, and predictive value. Observational study designs often include
      relative risk, odds ratios, relative risk reduction, attributable risk, number
      needed to treat, and forest plots. A critical component of drug literature
      evaluation is the understanding of the proper use of parametric and nonparametric
      statistical tests. Common parametric tests and their nonparametric equivalents
      are discussed.

PMID- 21182355
TI  - Measuring diabetes care in the national interdisciplinary primary care practice
      based research network (NIPC-PBRN).
AB  - STUDY OBJECTIVE: To assess diabetes care in a network of primary care practices
      that include pharmacist support by using a scoring system designed for the
      National Committee for Quality Assurance (NCQA) Diabetes Recognition Program
      (DRP) measures. DESIGN: Retrospective medical record review. DATA SOURCE: Subset
      of the National Interdisciplinary Primary Care Practice-Based Research Network
      (NIPC-PBRN). PATIENTS: A total of 1309 adults who were seen at 17 practices for
      an outpatient diabetes mellitus visit between January 1 and June 30, 2008.
      MEASUREMENTS AND MAIN RESULTS: Patient demographic data and NCQA DRP process and
      outcome measures (hemoglobin A(1c) [A1C], blood pressure, and low-density
      lipoprotein cholesterol [LDL] level measurements; eye and foot examinations;
      nephropathy assessment; and smoking status and cessation advice or treatment)
      were recorded. Points for each measure were compiled, and practices achieving a
      sufficient score for NCQA recognition (>= 75.0 points) were identified.
      Pharmacists were also surveyed regarding their services, participation in quality
      improvement initiatives, use of electronic medical records, and methods of data
      extraction. The relationships between DRP measures and quality improvement
      activities, pharmacist involvement in diabetes care, and use of electronic
      medical records were analyzed. The DRP outcome measures were satisfactory: mean
      +/- SD A1C 7.6% +/- 1.9%, LDL level 99.1 +/- 35.1 mg/dl, and systolic and
      diastolic blood pressures 130.2 +/- 18.1 and 74.4 +/- 10.8 mm Hg, respectively.
      Five practices (29%) achieved a sufficient score for NCQA recognition. No
      significant relationships were noted between DRP measures and participation in
      quality improvement, type of clinical pharmacy services, or use of electronic
      medical records (p>0.05). In a regression analysis, only electronic medical
      record use was significantly related to DRP measures (p=0.02). CONCLUSION:
      Diabetes care in the NIPC-PBRN appears satisfactory, but improvements are
      necessary if NCQA recognition is the goal. Use of electronic medical records was
      associated with better DRP measures.

PMID- 21182356
TI  - Effectiveness of a hypertension care management program provided by clinical
      pharmacists for veterans.
AB  - STUDY OBJECTIVE: To evaluate the effectiveness of a hypertension care management
      program provided by clinical pharmacists. DESIGN: Pre- and postintervention
      design with retrospective medical record review. SETTING: Tertiary care Veterans
      Affairs medical center and affiliated primary care clinics. PATIENTS: Five
      hundred seventy-three veterans with hypertension who were referred to the program
      between June 1, 2007, and May 31, 2008. INTERVENTION: Participation in the
      hypertension care management program provided by clinical pharmacists who met
      individually with patients, orchestrated drug therapy, and provided patient
      counseling. MEASUREMENTS AND MAIN RESULTS: The following data were collected from
      patients' medical records: demographics, date of program referral, dates of
      pharmacist visits, blood pressure at each visit, concurrent antihypertensive
      drugs and their dosages, drug changes at each visit, as well as patient education
      topics discussed during a visit. To ensure a minimum of 6 months of follow-up
      data for all patients, data collection continued through November 30, 2008, for a
      total study duration of 18 months. The primary study outcome was the difference
      between systolic and diastolic blood pressure measurements at the final
      pharmacist care management visit and those measurements at the initial pharmacist
      visit. Systolic blood pressure decreased from a mean +/- SD of 141.3 +/- 18.5 mm
      Hg at the initial pharmacist visit to 130.1 +/- 13.8 mm Hg at the final
      pharmacist visit, and diastolic blood pressure decreased from 79.1 +/- 12.2 to
      74.5 +/- 10.3 mm Hg (p<0.001 for both comparisons). The secondary outcome was the
      proportion of patients reaching blood pressure treatment goals at the final visit
      compared with the initial pharmacist visit. Of the 573 patients, 431 (75.2%)
      reached blood pressure treatment goals at the final visit (p <= 0.001) compared
      with 221 (38.6%) at the initial visit. The study patients had several comorbid
      diseases, including diabetes mellitus (196 patients [34.2%]) and chronic kidney
      disease (43 patients [7.5%]). Both study outcomes were also assessed for these
      subgroups. CONCLUSION: Patients referred to the hypertension care management
      program had a significant reduction in blood pressure, and most met their blood
      pressure treatment goals. This pharmacist-managed program may be an efficient
      method of care delivery to improve patient outcomes.

PMID- 21182352
TI  - Adenosine deaminases acting on RNA, RNA editing, and interferon action.
AB  - Adenosine deaminases acting on RNA (ADARs) catalyze adenosine (A) to inosine (I)
      editing of RNA that possesses double-stranded (ds) structure. A-to-I RNA editing
      results in nucleotide substitution, because I is recognized as G instead of A
      both by ribosomes and by RNA polymerases. A-to-I substitution can also cause
      dsRNA destabilization, as I:U mismatch base pairs are less stable than A:U base
      pairs. Three mammalian ADAR genes are known, of which two encode active
      deaminases (ADAR1 and ADAR2). Alternative promoters together with alternative
      splicing give rise to two protein size forms of ADAR1: an interferon-inducible
      ADAR1-p150 deaminase that binds dsRNA and Z-DNA, and a constitutively expressed
      ADAR1-p110 deaminase. ADAR2, like ADAR1-p110, is constitutively expressed and
      binds dsRNA. A-to-I editing occurs with both viral and cellular RNAs, and affects
      a broad range of biological processes. These include virus growth and
      persistence, apoptosis and embryogenesis, neurotransmitter receptor and ion
      channel function, pancreatic cell function, and post-transcriptional gene
      regulation by microRNAs. Biochemical processes that provide a framework for
      understanding the physiologic changes following ADAR-catalyzed A-to-I ( = G)
      editing events include mRNA translation by changing codons and hence the amino
      acid sequence of proteins; pre-mRNA splicing by altering splice site recognition
      sequences; RNA stability by changing sequences involved in nuclease recognition;
      genetic stability in the case of RNA virus genomes by changing sequences during
      viral RNA replication; and RNA-structure-dependent activities such as microRNA
      production or targeting or protein-RNA interactions.

PMID- 21182357
TI  - Effectiveness of biologic therapies for rheumatoid arthritis: an indirect
      comparisons approach.
AB  - STUDY OBJECTIVE: To compare the efficacy of biologic disease-modifying
      antirheumatic drugs (DMARDs) versus placebo with or without methotrexate, in
      treating rheumatoid arthritis. DESIGN: Comparative effectiveness analysis using
      an indirect treatment comparison (ITC) method in a Bayesian framework. PATIENTS:
      Adults with rheumatoid arthritis who had been enrolled in randomized controlled
      trials (RCTs) and had never failed biologic DMARD therapy. MEASUREMENTS AND MAIN
      RESULTS: Two random-effects logistic regression models, representing 6 and 12
      months of treatment, were created using RCTs identified in a literature search.
      Twenty-three RCTs (11,589 patients) were included in the 6-month model and 10
      RCTs (6051 patients) in the 12-month model. Nine biologic DMARDs in five
      therapeutic drug classes were included in the 6-month model, and six biologic
      DMARDs in three classes were included in the 12-month model. Our efficacy end
      point was the American College of Rheumatology 50% improvement criteria. In the 6
      month model, all biologic DMARDs and methotrexate were significantly more
      efficacious than placebo and ranked in the following order: certolizumab (median
      log odds ratio [OR] 2.6), tocilizumab (1.7), rituximab (1.6), infliximab (1.6),
      etanercept (1.4), adalimumab (1.4), golimumab (1.4), abatacept (1.2), anakinra
      (1.0), and methotrexate (0.8). Of 45 pairwise comparisons, certolizumab was
      significantly more efficacious than methotrexate, but no other comparisons were
      significant. The rank order in the 12-month analysis was certolizumab (median log
      OR 2.0), rituximab (2.0), adalimumab (1.4), infliximab (1.4), etanercept (0.9),
      abatacept (0.6), and methotrexate (0.8). Of the 21 pairwise comparisons, none
      were significant. The results of the model using therapeutic class revealed that
      each class was more efficacious than placebo. In pairwise comparisons, each class
      was more efficacious than methotrexate, but none was more efficacious than
      another. CONCLUSION: Use of emerging ITC methods enabled us to compare the
      efficacy of biologic DMARDs for the treatment of rheumatoid arthritis in the
      absence of direct head-to-head comparison trials. Our methods enabled us to rank
      order these treatments. Further analyses by drug and by therapeutic class suggest
      that biologic DMARDs are similarly efficacious.

PMID- 21182358
TI  - Nebulizer delivery of micafungin aerosols.
AB  - STUDY OBJECTIVES: To determine the optimal nebulization system for aerosolizing
      micafungin and to further assess the physiochemical properties of aerosolized
      micafungin. DESIGN: In vitro experiment. SETTING: University research center.
      NEBULIZERS: Pari LC Star, Hudson Updraft, Small Volume Nebulizer, and Aeroclipse
      II. MEASUREMENTS AND MAIN RESULTS: Using a commercially available cascade
      impactor, the four nebulizers were tested for their ability to deliver micafungin
      to the lungs. Mass median aerodynamic diameter (MMAD) and fine particle fraction
      (FPF) percent less than 3.3 MUm (FPF(3.3)) and less than 5.8 MUm (FPF(5.8)) were
      determined during two sampling periods for each of three trials of all
      nebulizers. The mean +/- standard error of the mean MMAD for the nebulizers
      ranged from 1.93 +/- 0.09 to 2.49 +/- 0.25 MUm; FPF(3.3) and FPF(5.8) were
      approximately 50% and 90%, respectively, for all nebulizers. CONCLUSION: Although
      all nebulizers appeared acceptable to deliver micafungin to the lungs, the Pari
      LC Star had the smallest MMAD and highest FPF(3.3) and FPF(5.8). These properties
      of the Pari LC Star should result in greater delivery of the aerosol to the
      lungs. Additional research on pulmonary delivery and clinical tolerability is
      warranted.

PMID- 21182359
TI  - Impact of iatrogenic, excessive, nondietary sodium administration in patients
      with acute heart failure exacerbation on hospital length of stay.
AB  - STUDY OBJECTIVE: To investigate the sources and quantities of nondietary sodium
      administration in patients hospitalized for acute heart failure exacerbation, and
      to evaluate the impact of sodium administration on length of stay. DESIGN:
      Retrospective analysis. SETTING: University-affiliated medical center. PATIENTS:
      One hundred and eighty-two consecutive patients admitted to a cardiac intensive
      care unit for acute heart failure exacerbation between January 1 and June 30,
      2009. MEASUREMENTS AND MAIN RESULTS: Drug therapy profiles of all patients were
      reviewed for sources and quantities of nondietary sodium administration, and the
      impact of sodium administration on hospital stay was analyzed. The mean +/- SD
      nondietary sodium load was 4.0 +/- 5.0 g/day. The predominant sources of sodium
      were intravenous 0.9% or 0.45% sodium chloride. The daily amount of sodium
      administration was directly related to the duration of hospital stay, with an
      average sodium load of 1.2 g/day correlating with hospital stays of up to 5 days,
      and an average of 2.6 g/day correlating with hospital stays of up to 10 days.
      CONCLUSION: We observed excessive sodium administration in patients hospitalized
      for acute exacerbation of heart failure. We speculate that reducing sodium
      administration in these patents may reduce length of hospital stay and cost of
      hospitalization.

PMID- 21182360
TI  - Heart failure caused by molecularly targeted therapies for cancer.
AB  - Cancer therapeutics is undergoing a revolution with the advent of new drugs that
      can selectively target molecules responsible for carcinogenesis and tumor growth.
      The type and mechanism of these targeting drugs vary. Some are small molecules
      that specifically target a binding site on a receptor or signal transduction
      molecule. Antibodies have been engineered to bind to the receptors or the
      corresponding ligands that mediate a critical cancer activity. In almost all
      cases, the intent is to inhibit or shut down a specific molecular pathway.
      Unprecedented activity against the cancer is seen without overt traditional
      toxicities such as alopecia, nausea and/or vomiting, and cytopenias.
      Unfortunately, an increase in toxicity has now become evident as more experience
      accumulates with the use of these drugs. In some cases, unexpected
      cardiotoxicities have arisen when these new drugs have been added to more
      conventional chemotherapies. Heart failure is the unfortunate manifestation for
      many of these toxicities. We outline the scope of this problem and examine the
      mechanisms of drug-induced heart failure. The distinctive signs and symptoms
      specific to each drug are described, and the diagnosis and treatment of the
      condition are discussed. Our aim is to allow the practitioner to recognize the
      unusual manifestations of heart failure in this setting in order to make a timely
      diagnosis and begin appropriate treatment measures.

PMID- 21182361
TI  - Valvular heart disease: a primer for the clinical pharmacist.
AB  - Valvular heart disease is a commonly encountered clinical condition that is not
      taught in most undergraduate and graduate pharmacy programs, leaving the
      practicing pharmacist without basic knowledge to expand on and subsequently apply
      to direct patient care. Unlike other areas of cardiology in which thousands of
      patients are recruited in many well-designed randomized clinical trials, data
      assessing treatments for valvular heart disease are limited and often consist of
      retrospective case series or observations. Our goal is to provide a basic
      overview of chronic valvular heart disease, with emphasis on describing the
      common conditions requiring surgery and the available options, as well as common
      pharmacologic therapies used in this patient population. Anomalies in valves can
      be broadly classified as stenosis and regurgitation. Depending on the valve and
      the type of anomaly, the impact on the cardiovascular system will vary.
      Understanding the hemodynamic consequences of aortic stenosis, aortic
      regurgitation, mitral stenosis, and mitral regurgitation is imperative to
      effectively counsel patients surrounding disease progression and self-monitoring,
      use of vasodilators, and prophylaxis for endocarditis and rheumatic fever.
      Further, patient characteristics factored into the choice of implanting either a
      bioprosthetic (tissue) or prosthetic (metal) valve encompass patient choice, life
      expectancy, and willingness or ability to accept lifelong anticoagulation
      therapy. The evolution of metal valves has resulted in newer generations under
      clinical study that have more laminar flow (minimizing interaction with blood
      products) and improved pyrolytic carbon (minimizing infection and interaction
      with blood products). Although antithrombotic therapy with warfarin is now
      mandatory in North America for all patients receiving metal valves, research is
      ongoing to assess the need with the most recent generation of valves.

PMID- 21182362
TI  - Current therapies for chronic hepatitis C.
AB  - Hepatitis C virus affects more than 180 million people worldwide and as many as 4
      million people in the United States. Given that most patients are asymptomatic
      until late in the disease progression, diagnostic screening and evaluation should
      be performed in patients who display high-risk behaviors associated with
      acquisition of hepatitis C. Chronic hepatitis C is associated with cirrhosis,
      hepatic failure, and death; therefore, treatment is aimed at reducing these
      complications, as well as improving quality of life and minimizing adverse
      effects. The American Association for the Study of Liver Diseases Practice
      Guidelines on the Diagnosis, Management, and Treatment of Hepatitis C represent
      the gold standard for guidance on the management of hepatitis C. Standard
      treatment for hepatitis C is peginterferon alpha in combination with ribavirin.
      Currently, two pegylated interferon products are approved by the U.S. Food and
      Drug Administration for the treatment of hepatitis C. The duration of therapy
      with peginterferon and ribavirin is dictated by viral genotype and virologic
      response. Additional therapies are under investigation for treatment of chronic
      hepatitis C and show early promise of comparative efficacy and fewer adverse
      effects. Special considerations in certain populations, including patients
      coinfected with human immunodeficiency virus, those with end-stage renal disease,
      injection drug users, pregnant women, and pediatric patients, should guide
      treatment decisions.

PMID- 21182366
TI  - Causes of camptocormia.
AB  - PURPOSE: To identify and highlight the variable causes of camptocormia. METHOD:
      Literature review. RESULTS: Camptocormia (bent spine syndrome) is an acquired
      postural disease characterised by forward flexion of the thoraco-lumbar spine.
      Camptocormia leads to lumbar kyphosis and increases during walking or standing
      and completely disappears in supine position. Camptocormia is multicausal due to
      central or peripheral nervous system disease, idiopathic or due to some rare
      conditions. Camptocormia is most frequently associated with Parkinson's disease.
      Other causes include dystonia, multisystem atrophy, Alzheimer's disease,
      myopathy, motor neuron disease, myasthenia or chronic inflammatory demyelinating
      polyneuropathy. Rare causes include adverse reactions of drugs, disc herniation,
      arthritis, spinal trauma, paraneoplastic disorder, or psychiatric disease (more
      rarely than previously thought). Camptocormia is diagnosed upon clinical
      investigations, imaging of the cerebrum or spine, electromyography or muscle
      biopsy. Treatment is limited on supportive conservative measures, to withdrawal
      of causative drugs, electroconvulsive therapy, surgical correction or deep brain
      stimulation and effective only in single patients. CONCLUSIONS: Camptocormia is
      organic in the vast majority of the cases due to neurological disease, or rarely
      drugs, trauma, orthopedic abnormalities or idiopathic.

PMID- 21182367
TI  - The influence of clinical terminology on self-efficacy for voice.
AB  - Self-efficacy is defined as one's belief in one's ability to carry out a specific
      behavior successfully. The current study's objective is to obtain initial
      evidence in support of the hypothesis that the terms 'vocal abuse/misuse' have
      the potential to harm self-efficacy for voice and may impact adherence with
      therapeutic directives. Teachers with voice problems were exposed to the terms
      'abuse/misuse' or 'phonotrauma/muscle tension' as describing the origin of common
      voice problems. Pre- and post-exposures, subjects completed a Voice Self-Efficacy
      Questionnaire that was specially designed for the study. Results provide
      preliminary support for the hypothesis that clinical exposure to 'abuse/misuse'
      terminology may harm normal increases in self-efficacy for voice that are
      generally expected following education about medical conditions.

PMID- 21182368
TI  - Publication practices of medical students at British medical schools: experience,
      attitudes and barriers to publish.
AB  - INTRODUCTION: With research playing a vital role in improving clinical practice,
      it is important that medical students understand the role of research and
      submitting articles for publication. Therefore, the aim of this study was to
      ascertain the experience, motivation and attitude of publishing of medical
      students. METHODS: A cross-sectional survey of British medical students from
      seven medical schools in the United Kingdom. RESULTS: Seventy-two of 515 had
      submitted an article for publication with a total of 124 articles being
      submitted. The main motivation to publish was for career progression. For the
      students that had not published, not having an opportunity to perform research
      was felt to be the main barrier. Only 49% of students had taken part in a
      research or audit project. Sixty-two percent of students stated they were not
      encouraged by the seniors to participate in research projects. From 515 medical
      students, only 88 students had submitted an article for a scientific meeting.
      CONCLUSIONS: Students have a positive attitude towards publishing and they feel
      it is important. However, it is clear that students require and would welcome
      education in writing papers and abstracts, skills that they will need in their
      postgraduate careers.

PMID- 21182369
TI  - Directing students to profound open-book test preparation: the relationship
      between deep learning and open-book test time.
AB  - BACKGROUND: Considering the growing amount of medical knowledge and the focus of
      medical education on acquiring competences, using open-book tests seems
      inevitable. A possible disadvantage of these tests is that students underestimate
      test preparation. AIMS: We examined whether students who used a deep learning
      approach needed less open-book test time, and how students performed on open-book
      questions asked in a closed-book setting. METHOD: Second- (N = 491) and third
      year students (N = 325) prepared half of the subject matter to be tested closed
      book and half to be tested open-book. In agreement with the Board of Examiners,
      some questions in the closed-book test concerned open-book subject matter, and
      vice versa. Data were gathered about test time, deep learning and preparation
      time. Repeated measurement analysis, t-tests and partial correlations were used
      to analyse the data. RESULTS: We found a negative relationship between deep
      learning and open-book test time for second-year students. Students scored the
      lowest on closed-book questions about open-book subject matter. CONCLUSIONS:
      Reduction of the available test time might force students to prepare longer and
      deeper for open-book tests. Further research is needed to identify variables that
      influence open-book test time and to determine how restrictive this time should
      be.

PMID- 21182370
TI  - Effects of interprofessional education on patient perceived quality of care.
AB  - BACKGROUND: Active patient-based learning by working together at an
      interprofessional clinical education ward (CEW) increases collaborative and
      professional competence among students. AIM: To assess the patients' perceptions
      of collaborative and communicative aspects of care when treated by
      interprofessional student teams as compared to usual care. METHOD: Patients
      treated by student teams (medical, nurse, physiotherapy and occupational therapy
      students) at a CEW comprised the intervention group. Patients treated at a
      regular ward were taken as controls. The patients answered a questionnaire
      representing collaborative and communicative aspects of care. Questionnaires from
      CEW (n = 84) and control (n = 62) patients were obtained (82% vs 73% response
      rates). RESULTS: CEW patients rated a significantly higher grade of own
      participation in decisions regarding treatment as compared to controls (p =
      0.006). They did further rate a higher grade of satisfaction with information
      regarding need of help at home (p = 0.003) and perceived that the CEW staff had
      taken their home situation into account at a higher grade in the preparation of
      discharge (p = 0.0002). Finally, CEW patients felt better informed (p = 0.02).
      CONCLUSION: Patients perceived a higher grade of quality of care as compared to
      controls with no signs of disadvantages when treated and informed by supervised
      interprofessional student teams.

PMID- 21182371
TI  - Students' views on the impact of peer physical examination and palpation as a
      pedagogic tool for teaching and learning living human anatomy.
AB  - BACKGROUND: Modern medical education teaching and learning approaches now lay
      emphasis on students acquiring knowledge, skills and attitudes relevant to
      medical practice. AIMS: To explore students' perceived impacts of using hands-on
      approaches involving peer/life model physical examination and palpation in
      teaching and learning living human anatomy on their practice of physical
      examination of real patients. METHODS: This study used exploratory focus groups
      and a questionnaire survey of years 3-5 medical students. RESULTS: The focus
      group discussions revealed new insights into the positive impacts of the hands-on
      approaches on students' clinical skills and professional attitudes when dealing
      with patients. Students' exposure to the hands-on approaches helped them to feel
      comfortable with therapeutically touching unclothed patients' bodies and
      physically examining them in the clinical environment. At least 60% of the
      questionnaire survey respondents agreed with the focus group participants on this
      view. Over 75% also agreed that the hands-on experiences helped them develop good
      professional attitudes in their encounter with patients. CONCLUSIONS: This study
      highlights the perceived educational value of the hands-on approaches as a
      pedagogic tool with a positive impact on students' clinical skills and
      professional attitudes that helps in easing their transition into clinical
      practice.

PMID- 21182372
TI  - Students' perceptions of educational environment in a medical school experiencing
      curricular transition in United Arab Emirates.
AB  - BACKGROUND: Gulf Medical College, UAE, underwent a major curriculum change from a
      discipline-based to an organ-based integrated curriculum. AIM: To compare
      students' perception of the educational environment in the discipline-based
      curriculum with that in the integrated curriculum. METHODS: Data was collected
      from second-year students (Group 1) in the discipline-based curriculum and in the
      subsequent year from second year students in the integrated curriculum (Group 2).
      The instrument used was Dundee Ready Education Environment Measure (DREEM).
      Scores were compared using Wilcoxon Rank Sum test. Data from second, third and
      fourth year students in the discipline-based curriculum were used to determine
      the total DREEM score for the school. RESULTS: The total DREEM score was
      significantly higher (p < 0.001) for Group 2 (135/200) when compared to Group
      1(116/200). Both groups unanimously perceived a positive educational environment.
      Although Group 2 showed significantly more satisfaction, they perceived an over
      emphasis of factual learning and a problem of cheating. Total DREEM score for the
      school was 120/200. CONCLUSION: This study shows that the organ system-based
      integrated curriculum is perceived to provide better educational environment than
      the discipline-based curriculum. However, areas like curriculum load and
      assessment strategies still require further fine tuning.

PMID- 21182373
TI  - The ethical and pedagogical effects of modeling "not-so-universal" precautions.
AB  - AIM: We sought to understand current medical students' levels of training and
      knowledge, and their attitudes regarding universal precautions practices and
      underlying professional and ethical issues. METHOD: A total of 54 US medical
      students at two schools were interviewed to determine the level of understanding
      and training students receive about universal precautions, their feelings about
      the effectiveness (or ineffectiveness) of universal precautions, the frequency
      and kinds of universal precautions used by healthcare professionals as observed
      by medical students, and students' perspectives about the lack of or inconsistent
      use of universal precautions. RESULTS: Pre-clinical students focused on safe-sex
      practices among students and professionals, as well as simple, important acts to
      protect oneself against infection and disease, such as hand-washing. Clinical
      students, on the other hand, had more exposure to observing and practicing
      universal precautions, thus presented us with more, in-depth responses pertaining
      to inconsistent and ineffective use of universal precautions among peers and role
      models. Several themes were noted from students' responses. CONCLUSION: This
      study confirms previously acquired data that universal precautions are not
      consistently or appropriately used by healthcare professionals, it is a
      significant and novel study in that it reveals a hidden, ethical, and clinical
      problem in medical education.

PMID- 21182374
TI  - The ethics of HIV testing and disclosure for healthcare professionals: what do
      our future doctors think?
AB  - AIM: This study examined future medical professionals' attitudes and beliefs
      regarding mandatory human immunodeficiency virus (HIV) testing and disclosure.
      METHOD: A total of 54 US medical students were interviewed regarding mandatory
      testing and disclosure of HIV status for both patient and health care
      professional populations. Interviews were qualitatively analyzed using thematic
      analysis by the first author and verified by the second author. RESULTS: Medical
      students considered a variety of perspectives, even placing themselves in the
      shoes of their patients or imagining themselves as a healthcare professional with
      HIV. Mixed opinions were presented regarding the importance of HIV testing for
      students coupled with a fear about school administration regarding HIV positive
      test results and the outcome of a student's career. Third- and fourth-year
      medical students felt that there should be no obligation to disclose one's HIV
      status to patients, colleagues, or employers. However, most of these students did
      feel that patients had an obligation to disclose their HIV status to healthcare
      professionals. CONCLUSION: This study gives medical educators a glimpse into what
      our future doctors think about HIV testing and disclosure, and how difficult it
      is for them to recognize that they can be patients too, as they are conflicted by
      professional and personal values.

PMID- 21182376
TI  - Simulation in medical education.
AB  - Studies in cognitive psychology inform us that the recall of information and its
      application are best when it is taught and rehearsed in environments similar to
      workplace. The healthcare professions are heavily task- and performance-based
      where non-technical skills, decision making and clinical reasoning are important
      alongside integrity, empathy and compassion. Most of these attributes are
      difficult to teach and assess in the traditional classrooms. Enhanced patient
      safety on one hand has to be the ultimate outcome of any medical curriculum while
      on the other hand, it itself can be potentially compromised in an apprenticeship
      based model of medical education. A range of simulation techniques are very well
      placed to be used alongside clinical placements. These can be employed to enhance
      learning of healthcare professionals in safe environments, without compromising
      the patient safety, while maintaining a high degree of realism. This article
      builds an argument for the use of simulation techniques to enhance patient safety
      and points the readers to the AMEE Guide No. 50 on simulation, which is written
      as a practical manual on building a simulation programme in healthcare education.

PMID- 21182375
TI  - Perceptions and valuation of a community-based education and service (COBES)
      program in Uganda.
AB  - BACKGROUND: Community-based education and service (COBES) has been promoted to
      improve the education of health professionals, particularly in low-resource
      settings. However, few evaluations have been performed to guide program
      development. AIM: This study assessed student and educator perceptions and
      valuation of a Ugandan COBES program. METHODS: We administered an internet-based
      survey to students, faculty, and site tutors associated with the Makerere
      University College of Health Sciences COBES program. RESULTS: 255 surveys were
      completed. Response rates varied (students, 188/684, 27.5%; faculty-site
      supervisors, 15/23, 65.2%; faculty general, 38/312, 12.2%; site tutors, 14/27,
      51.9%). Students valued the COBES program (93.5% some/high value). Tutors enjoyed
      their work (92.9% agreeing/strongly agreeing). Faculty (n = 53) felt COBES was
      valuable (90.2% agreeing/strongly agreeing). High student valuation was
      associated with high quality accommodation (aOR 4.7, 95% CI = 1.6-13.4), free
      accommodation (aOR 2.9, 95% CI = 1.2-6.8), and tutors who demonstrated enthusiasm
      for teaching (aOR 3.4, 95% CI = 1.1-10.0). Areas identified for improvement
      included financial support, student preparation, and tutor training, feedback,
      and supervision. CONCLUSION: In this study, COBES was perceived positively by
      students and educators and learning environment and quality of teaching both
      contributed to valuation of COBES. Well-implemented COBES programs may offer an
      opportunity to enhance health sciences education.

PMID- 21182377
TI  - If it matters, it produces controversy.

PMID- 21182378
TI  - Communication skills: an essential component of medical curricula. Part I:
      Assessment of clinical communication: AMEE Guide No. 51.
AB  - This AMEE Guide in Medical Education is Part 1 of a two part Guide covering the
      issues of Communication. This Guide has been written to provide guidance for
      those involved in planning the assessment of clinical communication and provides
      guidance and information relating to the assessment of various aspects of
      clinical communication; its underlying theory; its practical ability to show that
      an individual is competent and its relationship to students' daily performance.
      The advantages and disadvantages of assessing specific aspects of communication
      are also discussed. The Guide draws attention to the complexity of assessing the
      ability to communicate with patients and healthcare professionals, with issues of
      reliability and validity being highlighted for each aspect. Current debates
      within the area of clinical communication teaching are raised: when should the
      assessment of clinical communication occur in undergraduate medical education?;
      should clinical communication assessment be integrated with clinical skills
      assessment, or should the two be separate?; how important should the assessment
      of clinical communication be, and the question of possible failure of students if
      they are judged not competent in communication skills? It is the aim of the
      authors not only to provide a useful reference for those starting to develop
      their assessment processes, but also provide an opportunity for review and debate
      amongst those who already assess clinical communication within their curricula,
      and a resource for those who have a general interest in medical education who
      wish to learn more about communication skills assessment.

PMID- 21182379
TI  - Are journal clubs effective in supporting evidence-based decision making? A
      systematic review. BEME Guide No. 16.
AB  - BACKGROUND: Journal clubs (JCs) are a common form of interactive education in
      health care aiming to promote the uptake of research evidence into practice, but
      their effectiveness has not been established. OBJECTIVE: This systematic review
      aimed to determine whether the JC is an effective intervention in supporting
      clinical decision making. METHODS: We searched for studies which evaluated
      whether clubs promote changes in learner reaction, attitudes, knowledge, skills,
      behaviour or patient outcomes. We included undergraduate, postgraduate and
      practice JCs and excluded studies evaluating video/internet meetings or single
      meetings. RESULTS: Eighteen studies were included. Studies reported improvements
      in reading behaviour (N = 5/11), confidence in critical appraisal (N = 7/7),
      critical appraisal test scores (N = 5/7) and ability to use findings (N = 5/7).
      No studies reported on patient outcomes. Sixteen studies used self-reported
      measures, but only four studies used validated tests. Interventions were too
      heterogeneous to allow pooling. Realist synthesis identified potentially 'active
      educational ingredients', including mentoring, brief training in clinical
      epidemiology, structured critical appraisal tools, adult-learning principles,
      multifaceted teaching approaches and integration of the JC with other clinical
      and academic activities. CONCLUSION: The effectiveness of JCs in supporting
      evidence-based decision making is not clear. Better reporting of the intervention
      and a mixed methods approach to evaluating active ingredients are needed in order
      to understand how JCs may support evidence-based practice.

PMID- 21182380
TI  - How we offer all medical students training in basic teaching skills.

PMID- 21182381
TI  - Wooden's pyramid: building a hierarchy of skills for successful communication.
AB  - BACKGROUND: John Wooden, the legendary college basketball coach, created the
      "Pyramid of Success", which he constructed from 14 timeless character traits and
      interpersonal skills that are critical to competitive greatness. Wooden's pyramid
      is a powerful symbol that he and others have used for several decades as an
      educational tool to promote leadership and teamwork. AIM: This article proposes
      the "Pyramid of Relational Excellence (PRE)", patterned after Wooden's pyramid,
      as a mnemonic-based educational symbol for communication skills training. METHOD:
      Literature review, personal reflection. RESULTS: The PRE is constructed of four
      tiers with a total of 12 building blocks, with each successive tier built upon
      the one beneath it. The building blocks represent fundamental elements that are
      known to be critical to successful communication. CONCLUSIONS: The PRE is process
      oriented rather than task oriented and focuses exclusively on the face-to-face
      encounter. It therefore complements established communications curricula, such as
      the UK communication wheel and others, which are more comprehensive and task
      oriented. The PRE is constructed of timeless, fundamental principles. It is
      therefore particularly well suited for training medical students and residents.

PMID- 21182382
TI  - Learning to listen: improving students' communication with disabled people.
AB  - BACKGROUND: This report outlines the action research used to develop a workshop
      for interprofessional student groups to enhance listening skills. AIM: The
      project aimed to enable students to reflect interprofessionally on the human
      factors central to effective communication using the power of storytelling by
      disabled people and their carers. METHODS: Qualitative data from students and
      participating service users were collected using focus groups and one-to-one
      interviews over three pilot cycles. RESULTS: The results from each pilot informed
      the cyclical development of the project so that each stage of data collection
      informed the next stage. During the pilots, 20 interviews with service users were
      completed and a total of 109 students participated. Transcribed data were
      analysed using principles from grounded theory. Quantitative scored questions on
      students' learning were analysed using statistical package for the social
      sciences. CONCLUSIONS: Both students (health and social care) and users
      benefitted from the education process which delivered highly relevant explicit
      learning opportunities, with analysis of how to improve communication for safe
      practice. Students benefitted from meaningful interactions with service users who
      shared their experiences and gave feedback on students' communication skills. The
      final workshop design resulted in a learning model which reflects the human side
      of healthcare delivery.

PMID- 21182383
TI  - Predictive validity of the Biomedical Admissions Test: an evaluation and case
      study.
AB  - There has been an increase in the use of pre-admission selection tests for
      medicine. Such tests need to show good psychometric properties. Here, we use a
      paper by Emery and Bell [2009. The predictive validity of the Biomedical
      Admissions Test for pre-clinical examination performance. Med Educ 43:557-564] as
      a case study to evaluate and comment on the reporting of psychometric data in the
      field of medical student selection (and the comments apply to many papers in the
      field). We highlight pitfalls when reliability data are not presented, how simple
      zero-order associations can lead to inaccurate conclusions about the predictive
      validity of a test, and how biases need to be explored and reported. We show with
      BMAT that it is the knowledge part of the test which does all the predictive
      work. We show that without evidence of incremental validity it is difficult to
      assess the value of any selection tests for medicine.

PMID- 21182384
TI  - Comment on I. C. McManus, Eamonn Ferguson, Richard Wakeford, David Powis and
      David James (2011). Predictive validity of the BioMedical Admissions Test (BMAT):
      an evaluation and case study. Medical Teacher 33(1): (this issue).

PMID- 21182386
TI  - The BioMedical Admissions Test for medical student selection: issues of fairness
      and bias.
AB  - BACKGROUND: The BioMedical Admissions Test (BMAT) forms part of the undergraduate
      medical admission process at the University of Cambridge. The fairness of
      admissions tests is an important issue. AIMS: Aims were to investigate the
      relationships between applicants' background variables and BMAT scores, whether
      they were offered a place or rejected and, for those admitted, performance on the
      first year course examinations. METHOD: Multilevel regression models were
      employed with data from three combined applicant cohorts. Admission rates for
      different groups were investigated with and without controlling for BMAT
      performance. The fairness of the BMAT was investigated by determining, for those
      admitted, whether scores predicted examination performance equitably. RESULTS:
      Despite some differences in applicants' BMAT performance (e.g. by school type and
      gender), BMAT scores predicted mean examination marks equitably for all
      background variables considered. The probability of achieving a 1st class
      examination result, however, was slightly under-predicted for those admitted from
      schools and colleges entering relatively few applicants. Not all differences in
      admission rates were accounted for by BMAT performance. However, the test
      constitutes only one part of a compensatory admission system in which other
      factors, such as interview performance, are important considerations. CONCLUSION:
      Results are in support of the equity of the BMAT.

PMID- 21182387
TI  - Does Saudi Arabia need an Abraham Flexner?

PMID- 21182388
TI  - Saudi Arabia does not need an Abraham Flexner.

PMID- 21182389
TI  - Is there a place for music in medical school?
AB  - Music permeates the medical literature regarding disease therapy. However, there
      are only few articles concerning music as a tool for development of cultural
      competency and interpersonal relations. We share our experience of forming a
      musical act of students and faculty at a medical school. We believe that this
      group has encouraged medical humanism and enhanced communication in the learning
      environment.

PMID- 21182390
TI  - Learning surface anatomy: which learning approach is effective in an integrated
      PBL curriculum?
AB  - BACKGROUND: Understanding surface anatomy and surface markings are integral for
      introducing clinical sciences. AIM: This study aimed to assess which learning
      approach is effective in learning surface anatomy. METHOD: First-year medical
      students were randomly assigned into two groups and asked to complete an MCQs
      quiz covering surface anatomy of the abdomen (pre-test). Each student worked on
      his/her own in each group. Group A students (n = 70) were then provided with a
      reading material and two images of the abdomen printed on A4 size paper. Students
      were asked to study the reading material and use the image of the abdomen to draw
      and label the surface anatomy of six abdominal organs. Group B students (n = 74)
      were provided with the same reading material but were asked to answer short
      answer questions. After 45 minutes, the reading material and answers were
      collected from both groups and student's performance was compared using the same
      sets of MCQs (post-test). RESULTS: Students from both groups showed significant
      improvement in their post-test scores compared to their pre-test scores. Also the
      means for paired samples were significantly higher in Group A compared to Group
      B. A small number of students in both groups scored <= 2 in the pre-test and
      failed the post-test. CONCLUSION: While both techniques improved students'
      scores; learning by drawing surface anatomy of abdominal organs showed higher
      scores.

PMID- 21182391
TI  - The uptake of podcasting and portable media players amongst UK medical students.

PMID- 21182392
TI  - Is it ok to say 'no'?

PMID- 21182394
TI  - Pharmacokinetics of felbinac after intravenous administration of felbinac
      trometamol in rats.
AB  - Felbinac trometamol (trishydroxymethylaminomethane 4-biphenylacetate) is a new
      water-soluble salt of felbinac currently undergoing clinical evaluation as an
      intravenous (i.v.) formulation for the treatment of severe post-operative pain.
      This article reports the pharmacokinetics of felbinac after i.v. administration
      of felbinac trometamol in Sprague-Dawley rats. The maximum plasma concentration
      (C(0)) and area under the plasma concentration-time curve (AUC) of felbinac
      administered at doses of 3.36, 8.40 and 21.0 mg/kg felbinac trometamol increased
      linearly with dose. Felbinac was highly protein bound (~95%) at plasma
      concentrations up to 75 MUg/ml and extensively metabolized with only small
      amounts being excreted unchanged in urine (0.318%), feces (0.530%) and bile
      (0.465%). 4'-Hydroxyfelbinac was the principal metabolite in urine, feces and
      bile together with felbinac glucuronide, 4'-hydroxyfelbinac glucuronide and
      sulfate. The majority of the administered dose was excreted in urine (63.6%)
      mostly as 4'-hydroxyfelbinac. Total drug in urine and feces accounted for about
      72% of the dose. It would appear that felbinac trometamol has the potential to
      replace lipid-based NSAID formulations and progress to clinical evaluation.

PMID- 21182395
TI  - Preclinical absorption, distribution, metabolism, excretion, and pharmacokinetic
      pharmacodynamic modelling of N-(4-(3-((3S,4R)-1-ethyl-3-fluoropiperidine-4
      ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3
      oxo-2,3-dihydropyridazine-4-carboxamide, a novel MET kinase inhibitor.
AB  - GNE-A (AR00451896; N-(4-(3-((3S,4R)-1-ethyl-3-fluoropiperidine-4-ylamino)-1H
      pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3
      dihydropyridazine-4-carboxamide) is a potent, selective MET kinase inhibitor
      being developed as a potential drug for the treatment of human cancers. Plasma
      clearance was low in mice and dogs (15.8 and 2.44 mL/min/kg, respectively) and
      moderate in rats and monkeys (36.6 and 13.9 mL/min/kg, respectively). The volume
      of distribution ranged from 2.1 to 9.0 L/kg. The mean terminal elimination half
      life ranged from 1.67 h in rats to 16.3 h in dogs. Oral bioavailability in rats,
      mice, monkeys, and dogs were 11.2%, 88.0%, 72.4%, and 55.8%, respectively.
      Allometric scaling predicted a clearance of 1.3-7.4 mL/min/kg and a volume of
      distribution of 4.8-11 L/kg in human. Plasma protein binding was high (96.7-99.0%
      bound). Blood-to-plasma concentration ratios (0.78-1.46) indicated that GNE-A did
      not preferentially distribute into red blood cells. Transporter studies in MDCKI
      MDR1 and MDCKII-Bcrp1 cells suggested that GNE-A is likely a substrate for MDR1
      and BCRP. Pharmacokinetic-pharmacodynamic modelling of tumour growth inhibition
      in MET-amplified EBC-1 human non-small cell lung carcinoma tumour xenograft mice
      projected oral doses of 5.6 and 13 mg/kg/day for 50% and 90% tumour growth
      inhibition, respectively. Overall, GNE-A exhibited favourable preclinical
      properties and projected human dose estimates.

PMID- 21182396
TI  - The versatility of haematopoietic stem cells: implications for leukaemia.
AB  - To understand the origins, and disease progression, of leukaemia we first need a
      clear idea of how the progeny of haematopoietic stem/precursor cells normally
      choose their fates. For about 30 years, 'classical' models of blood cell
      development have envisaged a branching tree with two trunks representing the two
      major families of cells: myeloid/erythroid and lymphoid. Recent debate about this
      apparent dichotomy has given rise to new models of haematopoiesis and new ways of
      viewing stem-cell behaviour. These suggest that stem and progenitor cells are
      more versatile than was first appreciated, so there can be multiple routes to one
      type of end cell. An important aspect of this versatility during haematopoiesis
      is that progenitor cells retain an unexpected portfolio of clandestine lineage
      potentials even when they seem to have progressed quite far along a particular
      developmental pathway. Here we examine this decision-making process and ask
      whether, developmentally, leukaemia stem cells are equally or less versatile than
      their normal counterparts.

PMID- 21182398
TI  - IXth International Symposium on Thysanoptera and Tospoviruses. 31st August - 4th
      September 2009, Sea World Resort, Queensland, Australia. Abstracts.

PMID- 21182399
TI  - Down-regulation of circadian clock gene period 2 in uterine endometrial stromal
      cells of pregnant rats during decidualization.
AB  - Circadian rhythms are modulated in a variety of peripheral tissues, including in
      the uterus where endometrial stromal cells (UESCs) undergo proliferation and
      differentiation (decidualization) during gestation. Here the authors focused on
      circadian rhythms in UESCs during implantation and decidualization in rodents. As
      revealed by analyses of cultured UESCs from pregnant Per2 promoter-dLuc
      transgenic rats, Per2 oscillation of ~24  h was observed in response to
      dexamethasone. Per2 oscillation was enhanced in UESCs during implantation,
      whereas they were attenuated during decidualization. In vivo studies showed that
      PER2 protein in the uteri displayed a peak at zeitberger time 4 (ZT 4) (day 4.50
      of gestation) and a trough at ZT 12 (day 4.83), indicating its circadian
      rhythmicity. Conversely, no significant circadian rhythm of the PER2 protein was
      observed during decidualization. Fluorescent immunohistochemical studies also
      supported circadian rhythmicity of the PER2 protein in its intracellular
      distribution. In accordance with Per2 mRNA expression, a circadian rhythm of
      vascular endothelial growth factor (Vegf) gene expression, having several E-box
      or E-box-like sites at the upstream of the transcription start site, was observed
      during implantation, showing a peak at ZT 0 and a trough at ZT 12. In contrast,
      Vegf mRNA expression displayed no circadian rhythm during decidualization.
      Collectively, the present results prove that Per2 oscillation is down-regulated
      in UESCs during decidualization. It is strongly suggested that cellular
      differentiation in UESCs interferes with circadian clockwork.

PMID- 21182400
TI  - The luteinizing hormone surge regulates circadian clock gene expression in the
      chicken ovary.
AB  - The molecular circadian clock mechanism is highly conserved between mammalian and
      avian species. Avian circadian timing is regulated at multiple oscillatory sites,
      including the retina, pineal, and hypothalamic suprachiasmatic nucleus (SCN).
      Based on the authors' previous studies on the rat ovary, it was hypothesized that
      ovarian clock timing is regulated by the luteinizing hormone (LH) surge. The
      authors used the chicken as a model to test this hypothesis, because the timing
      of the endogenous LH surge is accurately predicted from the time of oviposition.
      Therefore, tissues can be removed before and after the LH surge, allowing one to
      determine the effect of LH on specific clock genes. The authors first examined
      the 24-h expression patterns of the avian circadian clock genes of Bmal1, Cry1,
      and Per2 in primary oscillatory tissues (hypothalamus and pineal) as well as
      peripheral tissues (liver and ovary). Second, the authors determined changes in
      clock gene expression after the endogenous LH surge. Clock genes were
      rhythmically expressed in each tissue, but LH influenced expression of these
      clock genes only in the ovary. The data suggest that expression of ovarian
      circadian clock genes may be influenced by the LH surge in vivo and directly by
      LH in cultured granulosa cells. LH induced rhythmic expression of Per1 and Bmal1
      in arrhythmic, cultured granulosa cells. Furthermore, LH altered the phase and
      amplitude of clock gene rhythms in serum-shocked granulosa cells. Thus, the LH
      surge may be a mechanistic link for communicating circadian timing information
      from the central pacemaker to the ovary.

PMID- 21182397
TI  - Molecular mechanisms for regulation of intestinal calcium absorption by vitamin D
      and other factors.
AB  - Optimal intestinal calcium (Ca) absorption is necessary for the protection of
      bone and the prevention of osteoporosis. Ca absorption can be represented as the
      sum of a saturable pathway and a non-saturable pathway that is primarily
      dependent upon luminal Ca concentration. While models have been proposed to
      describe these transport components, significant gaps still exist in our
      understanding of these processes. Habitual low intake of Ca up-regulates the
      saturable transport pathway, a process mediated by increased renal production of
      1,25 dihydroxyvitamin D (1,25(OH)(2)D). Consistent with this, low vitamin D
      status as well as deletion/mutation of the vitamin D receptor (VDR) or 25
      hydroxyvitamin D-1alpha hydroxylase (CYP27B1) genes limit Ca absorption by
      reducing the saturable pathway. There is some evidence that non-saturable Ca
      absorption in the ileum is also regulated by vitamin D status, but the mechanism
      is unclear. Treatment with a number of hormones can regulate Ca absorption in
      vivo (e.g. parathyroid hormone (PTH), thyroid hormone, growth hormone
      (GH)/insulin-like growth factor I (IGF-1), estrogen, testosterone). However, some
      of these actions are indirect (i.e. mediated through the regulation of vitamin D
      metabolism or signaling), whereas only a few (e.g. estrogen, IGF-1) have been
      shown to persist in the absence of vitamin D signaling.

PMID- 21182401
TI  - Expression of circadian clock and melatonin receptors within cultured rat
      cardiomyocytes.
AB  - Melatonin, the pineal gland hormone, provides entrainment of many circadian
      rhythms to the ambient light/dark cycle. Recently, cardiovascular studies have
      demonstrated melatonin interactions with many physiological processes and
      diseases, such as hypertension and cardiopathologies. Although membrane melatonin
      receptors (MT1, MT2) and the transcriptional factor RORalpha have been reported
      to be expressed in the heart, there is no evidence of the cell-type expressing
      receptors as well as the possible role of melatonin on the expression of the
      circadian clock of cardiomyocytes, which play an important role in cardiac
      metabolism and function. Therefore, the aim of this study was to evaluate the
      mRNA and protein expressions of MT1, MT2, and RORalpha and to determine whether
      melatonin directly influences expression of circadian clocks within cultured rat
      cardiomyocytes. Adult rat cardiomyocyte cultures were created, and the cells were
      stimulated with 1 nM melatonin or vehicle. Gene expressions were assayed by real
      time polymerase chain reaction (PCR). The mRNA and protein expressions of
      membrane melatonin receptors and RORalpha were established within adult rat
      cardiomyocytes. Two hours of melatonin stimulation did not alter the expression
      pattern of the analyzed genes. However, given at the proper time, melatonin kept
      Rev-erbalpha expression chronically high, specifically 12 h after melatonin
      treatment, avoiding the rhythmic decline of Rev-erbalpha mRNA. The blockage of
      MT1 and MT2 by luzindole did not alter the observed melatonin-induced expression
      of Rev-erbalpha mRNA, suggesting the nonparticipation of MT1 and MT2 on the
      melatonin effect within cardiomyocytes. It is possible to speculate that
      melatonin, in adult rat cardiomyocytes, may play an important role in the light
      signal transduction to peripheral organs, such as the heart, modulating its
      intrinsic rhythmicity.

PMID- 21182403
TI  - Circadian rhythms of self-feeding and locomotor activity in zebrafish (Danio
      Rerio).
AB  - To investigate daily feeding rhythms in zebrafish, the authors have developed a
      new self-feeding system with an infrared photocell acting as a food-demand
      sensor, which lets small-size fish such as zebrafish trigger a self-feeder. In
      this paper, the authors used eight groups of 20 fish. Locomotor activity rhythms
      were also investigated by means of infrared sensors. Under a 12 h:12 h light (L)
      dark (D) cycle, zebrafish showed a clear nocturnal feeding pattern (88.0% of the
      total daily food-demands occurring in the dark phase), concentrated during the
      last 4 h of the dark phase. In contrast, locomotor activity was mostly diurnal
      (88.2% of total daily activity occurring in the light phase). Moreover, both
      feeding and locomotor rhythms were endogenously driven, as they persisted under
      free-running conditions. The average period length (tau) of the locomotor and
      feeding rhythms was shorter (tau = 22.9 h) and longer (tau = 24.6 h) than 24 h,
      respectively. During the time that food availability was restricted, fish could
      only feed during ZT0-ZT12 or ZT12-ZT16. This resulted in feeding activity being
      significantly modified according to feeding time, whereas the locomotor activity
      pattern remained synchronized to the LD cycle and did not change during this
      trial. These findings revealed an independent phasing between locomotor and
      feeding activities (which were mostly nocturnal or diurnal, respectively), thus
      supporting the concept of multioscillatory control of circadian rhythmicity in
      zebrafish.

PMID- 21182402
TI  - Circadian periods of sensitivity for ramelteon on the onset of running-wheel
      activity and the peak of suprachiasmatic nucleus neuronal firing rhythms in
      C3H/HeN mice.
AB  - Ramelteon, an MT(1)/MT(2) melatonin receptor agonist, is used for the treatment
      of sleep-onset insomnia and circadian sleep disorders. Ramelteon phase shifts
      circadian rhythms in rodents and humans when given at the end of the subjective
      day; however, its efficacy at other circadian times is not known. Here, the
      authors determined in C3H/HeN mice the maximal circadian sensitivity for
      ramelteon in vivo on the onset of circadian running-wheel activity rhythms, and
      in vitro on the peak of circadian rhythm of neuronal firing in suprachiasmatic
      nucleus (SCN) brain slices. The phase response curve (PRC) for ramelteon (90
      ug/mouse, subcutaneous [sc]) on circadian wheel-activity rhythms shows maximal
      sensitivity during the late mid to end of the subjective day, between CT8 and
      CT12 (phase advance), and late subjective night and early subjective day, between
      CT20 and CT2 (phase delay), using a 3-day-pulse treatment regimen in C3H/HeN
      mice. The PRC for ramelteon resembles that for melatonin in C3H/HeN mice, showing
      the same magnitude of maximal shifts at CT10 and CT2, except that the range of
      sensitivity for ramelteon (CT8-CT12) during the subjective day is broader.
      Furthermore, in SCN brain slices in vitro, ramelteon (10 pM) administered at CT10
      phase advances (5.6 +/- 0.29 h, n = 3) and at CT2 phase delays (-3.2 +/- 0.12 h,
      n = 6) the peak of circadian rhythm of neuronal firing, with the shifts being
      significantly larger than those induced by melatonin (10 pM) at the same
      circadian times (CT10: 2.7 +/- 0.15 h, n = 4, p < .05; CT2: -1.13 +/- 0.08 h, n =
      6, p < .001, respectively). The phase shifts induced by both melatonin and
      ramelteon in the SCN brain slice at either CT10 or CT2 corresponded with the
      period of sensitivity observed in vivo. In conclusion, melatonin and ramelteon
      showed identical periods of circadian sensitivity at CT10 (advance) and CT2
      (delay) to shift the onset of circadian activity rhythms in vivo and the peak of
      SCN neuronal firing rhythms in vitro.

PMID- 21182404
TI  - Rhythmic birds show a better social integration than arrhythmic birds.
AB  - The activity rhythms of Japanese quail vary from one individual to another.
      Performing a divergent selection, we obtained one line of quail expressing a
      robust circadian rhythmicity of feeding activity (R) and one line of quail
      expressing circadian arrhythmicity of feeding activity (A). We questioned whether
      the endogenous rhythmicity of an individual could predict its integration in a
      group. For that, we introduced either an R- or an A-line chick into stable groups
      of standard chicks. First, we evaluated proximity and synchronization of the
      introduced chicks on the activities of the other group members. R-chicks remained
      spatially and temporally closer to other group members than did A-chicks. Second,
      we evaluated interactions of the introduced chicks and the level of their
      acceptance by the other group members. R-chicks were more competent to gain
      access to food than were A-chicks, and separation from their group stressed R
      chicks more than A-chicks. Last, successive introductions assessed age effects:
      before, around, and after dispersal time (~11th day of chicks' life). Most
      differences between R- and A-chicks were observed between their 7th and 15th day
      of life. In conclusion, individual endogenous rhythms predict social integration.

PMID- 21182405
TI  - Re-entrainment behavior of Djungarian hamsters (Phodopus sungorus) with different
      rhythmic phenotype following light-dark shifts.
AB  - Djungarian hamsters bred at the authors' institute reveal two distinct circadian
      phenotypes, the wild-type (WT) and DAO type. The latter is characterized by a
      delayed activity-onset, probably due to a deficient mechanism for photic
      entrainment. Experiments with zeitgeber shifts have been performed to gain
      further insight into the mechanisms underlying this phenomenon. Advancing and
      delaying phase shifts were produced by a single lengthening or shortening of the
      dark (D) or light (L) time by 6 h. Motor activity was recorded by passive
      infrared motion detectors. All WT hamsters re-entrained following various
      zeitgeber shifts and nearly always in the same direction as the zeitgeber shift.
      On the other hand, a considerable proportion of the DAO animals failed to re
      entrain and showed, instead, diurnal, arrhythmic, or free-running activity
      patterns. All but one of those hamsters that re-entrained did so by delaying
      their activity rhythm independently of the direction of the LD shift.
      Resynchronization occurred faster following a delayed than an advanced shift and
      also after changes of D rather than L. WT animals tended to re-entrain faster,
      particularly following a zeitgeber advance (where DAO hamsters re-entrained by an
      18-h phase delay instead of a 6-h phase advance). However, the difference between
      phenotypes was statistically significant only with a shortening of L. To better
      understand re-entrainment behavior, Type VI phase-response curves (PRCs) were
      constructed. To do this, both WT and DAO animals were kept under LD conditions,
      and light pulses (15 min, 100 lux) were applied at different times of the dark
      span. In WT animals, activity-offset always showed phase advances, whereas
      activity-onset was phase delayed by light pulses applied during the first half of
      the dark time and not affected by light pulses applied during the second half.
      When the light pulse was given at the beginning of D, activity-onset responded
      more strongly, but light pulses given later in D produced significant changes
      only in activity-offset. In accord with the delayed activity-onset in DAO
      hamsters, no or only very weak phase-responses were observed when light pulses
      were given during the first hours of D. However, the second part of the PRCs was
      similar to that of WT hamsters, even though it was compressed to an interval of
      only a few hours and the shifts were smaller. Due to these differences, the first
      light-on or light-off following an LD shift fell into different phases of the PRC
      and thus caused different re-entrainment behavior. The results show that it is
      not only steady-state entrainment that is compromised in DAO hamsters but also
      their re-entrainment behavior following zeitgeber shifts.

PMID- 21182406
TI  - Light masking in the field: an experiment with nocturnal and diurnal spiny mice
      under semi-natural field conditions.
AB  - Light masking has been studied almost exclusively in the laboratory. The authors
      populated four field enclosures with locally coexisting nocturnal Acomys
      cahirinus and diurnal A. russatus, and monitored their body temperatures (T(b))
      using implanted temperature-sensitive radio transmitters. A 3-h light pulse was
      initiated at the beginning of two consecutive nights; preceding nights were
      controls. A. cahirinus T(b) and calculated activity levels decreased
      significantly during the light pulse, demonstrating a negative light masking
      response (light effect on T(b): -0.32  degrees C +/- 0.15  degrees C; average
      calculated activity records during the light pulse: 7 +/- 1.53, control: 9.8 +/-
      1.62). Diurnal A. russatus did not respond to the light pulse. We conclude that
      light masking is not an artifact of laboratory conditions but represents a
      natural adaptive response in free-living populations.

PMID- 21182407
TI  - Does the modern urbanized sleeping habitat pose a breast cancer risk?
AB  - Due to its disruptive effects on circadian rhythms and sleep deprivation at
      night, shiftworking is currently recognized as a risk factor for breast cancer
      (BC). As revealed by the present analysis based on a comparative case-control
      study of 1679 women, exposure to light-at-night (LAN) in the "sleeping habitat"
      is significantly associated with BC risk (odds ratio [OR] = 1.220, 95% confidence
      interval [CI] = 1.118-1.311; p < .001), controlling for education, ethnicity,
      fertility, and alcohol consumption. The novelty of the present research is that,
      to the best of the authors' knowledge, it is the first study to have identified
      an unequivocal positive association between bedroom-light intensity and BC risk.
      Thus, according to the results of the present study, not only should artificial
      light exposure in the working environment be considered as a potential risk
      factor for BC, but also LAN in the "sleeping habitat."

PMID- 21182408
TI  - A psychometric assessment of the Circadian Amplitude and Phase Scale.
AB  - The Circadian Amplitude and Phase Scale (CAPS) is a new self-report tool that
      aims to assess amplitude and phase. The CAPS consists of three factors made up of
      38 items. Amplitude is posited to be assessed via two of these factors: time
      awareness (TA) and/or strength of preference (SOP). The remaining factor, phase,
      is assessed via the existing Preferences Scale (PS). Given there is no published
      research using this measure, the authors undertook two studies to examine its
      psychometric properties and construct validity. In a sample of 351 North American
      students, the authors identified a three-factor 34-item model using principal
      components analysis. The components explained 39% of the variance, and scale
      reliability ranged from 0.73 (SOP) to 0.88 (PS). The correlations between the
      components were small, suggesting they are each assessing different constructs.
      Thus, it is unlikely TA and SOP may both be indicators of amplitude. The
      distributions for each scale were divided into two groups (<= 25th and >= 75th
      percentiles), and these groups were used to assess construct validity using
      alertness ratings by time-of-day. The results from a multivariate general linear
      model indicated a significant difference (p < .001) in sleepiness ratings by time
      of-day for the PS scale only. In the second study, the authors applied
      confirmatory factor analysis in an attempt to replicate the factor structure
      identified in the student sample in a working sample (n = 388). The results
      suggested the model fit was not optimal. Subsequent analysis suggested a 26-item
      model was a better fit, but it also was not optimal. The intercorrelations
      between the factors were larger than in the student sample but again small,
      indicating the constructs are independent measures. The inability to replicate
      the factor structure is most likely explained by the differences in the sample
      characteristics of age, sex, and perhaps difficulty in interpreting the items.
      The limitations of these studies are discussed and recommendations for future
      studies are made.

PMID- 21182409
TI  - Connective tissue studies, and with a focus on collagen structure.

PMID- 21182410
TI  - Molecular and structural mapping of collagen fibril interactions.
AB  - The fibrous collagens form the structural basis of all mammalian connective
      tissues, including the vasculature, dermis, bones, tendons, cartilage, and those
      tissues that support organs such as the heart, kidneys, liver, and lungs. The
      helical structure of collagen has been extensively studied but in addition to its
      helical character, its molecular packing arrangement (in its aggregated or
      fibrillar form) and the presence of specific amino acid sequences govern
      collagen's in vivo functions. Collagen's molecular packing arrangement helps
      control cellular communication, attachment and movement, and conveys its tissue
      specific biomechanical properties. Recent progress in understanding collagen's
      molecular packing, fibrillar structure, domain organization, and extracellular
      matrix (ECM) interactions in light of X-ray fiber diffraction data provides
      significant new insights into how the ECM is organized and functions. In this
      review, the hierarchy of fibrillar collagen structure is discussed in the context
      of how this organization affects ECM-"ligand" interactions, with specific
      attention to collagenolysis, integrins, fibronection, glycoprotein VI receptor
      (GPVI), and proteoglycans (PG). Understanding the complex structure of collagen
      and its attached ligands should provide new insights into tissue growth,
      development, regeneration, and disease.

PMID- 21182411
TI  - Nanofabrication techniques for controlled drug-release devices.

PMID- 21182412
TI  - Cancer optical imaging using fluorescent nanoparticles.

PMID- 21182415
TI  - The Carolina Center of Cancer Nanotechnology Excellence: past accomplishments and
      future perspectives.
AB  - The Carolina Center of Cancer Nanotechnology Excellence (C-CCNE) is funded by the
      National Cancer Institute and is based at the University of North Carolina. The C
      CCNE features interactions between physical and biological scientists in a series
      of projects and cores that work together to quickly harness innovations in
      nanotechnology for the early diagnosis and treatment of cancer. Two key focus
      areas of the C-CCNE are, first, the selective delivery of drugs and imaging
      agents utilizing advanced nanoparticle technology, and second, novel approaches
      to imaging and radiotherapy utilizing carbon nanotube-based x-ray sources.

PMID- 21182417
TI  - Magnetic carbon nanotubes: a new tool for shepherding mesenchymal stem cells by
      magnetic fields.
AB  - AIMS: We investigated the interaction between magnetic carbon nanotubes (CNTs)
      and mesenchymal stem cells (MSCs), and their ability to guide these intravenously
      injected cells in living rats by using an external magnetic field. MATERIALS &
      METHODS: Multiwalled CNTs were used to treat MSCs derived from rat bone marrow.
      Cytotoxicity induced by nanotubes was studied using the WST-1 proliferation and
      Hoechest 33258 apoptosis assays. The effects of nanotubes on MSCs were evaluated
      by monitoring the effects on cellular growth rates, immunophenotyping and
      differentiation, and on the arrangement of cytoskeletal actin. MSCs loaded with
      nanotubes were injected in vivo in the portal vein of rats driving their
      localization in the liver by magnetic field. An histological analysis was
      performed on the liver, lungs and kidneys of all animals. RESULTS: CNTs did not
      affect cell viability and their ability to differentiate in osteocytes and
      adipocytes. Both the CNTs and the magnetic field did not alter the cell growth
      rate, phenotype and cytoskeletal conformation. CNTs, when exposed to magnetic
      fields, are able to shepherd MSCs towards the magnetic source in vitro. Moreover,
      the application of a magnetic field alters the biodistribution of CNT-labelled
      MSCs after intravenous injection into rats, increasing the accumulation of cells
      into the target organ (liver). CONCLUSION: Multiwalled CNTs hold the potential
      for use as nanodevices to improve therapeutic protocols for transplantation and
      homing of stem cells in vivo. This could pave the way for the development of new
      strategies for the manipulation/guidance of MSCs in regenerative medicine and
      cell transplantation.

PMID- 21182416
TI  - Polyelectrolyte complex optimization for macrophage delivery of redox enzyme
      nanoparticles.
AB  - BACKGROUND: We posit that cell-mediated drug delivery can improve transport of
      therapeutic enzymes to the brain and decrease inflammation and neurodegeneration
      seen during Parkinson's disease. Our prior works demonstrated that macrophages
      loaded with nanoformulated catalase ('nanozyme') then parenterally injected
      protect the nigrostriatum in a murine model of Parkinson's disease. Packaging of
      catalase into block ionomer complex with a synthetic polyelectrolyte block
      copolymer precludes enzyme degradation in macrophages. METHODS: We examined
      relationships between the composition and structure of block ionomer complexes
      with a range of block copolymers, their physicochemical characteristics, and
      loading, release and catalase enzymatic activity in bone marrow-derived
      macrophages. RESULTS: Formation of block ionomer complexes resulted in improved
      aggregation stability. Block ionomer complexes with epsilon-polylysine and poly(L
      glutamic acid)-poly(ethylene glycol) demonstrated the least cytotoxicity and high
      loading and release rates. However, these formulations did not efficiently
      protect catalase inside macrophages. CONCLUSION: Nanozymes with polyethyleneimine
      and poly(L-lysine)(10)-poly(ethylene glycol) provided the best protection of
      enzymatic activity for cell-mediated drug delivery.

PMID- 21182419
TI  - Targeted removal of migratory tumor cells by functionalized magnetic
      nanoparticles impedes metastasis and tumor progression.
AB  - AIMS: To slow tumor progression by reducing migratory tumor cell burden using
      magnetic nanoparticles (MNPs) functionalized with ligands selective for malignant
      cell surface receptors. MATERIALS & METHODS: Three groups of female C57BL/6 mice
      (control group I, control group II and experimental group) were intraperitoneally
      injected with a murine ovarian cancer cell line (ID8[VEGF160(+)/eGFP(+)]).
      Control group I received no intervention. MNPs were functionalized with ephrin-A1
      mimetic peptides selective for the EphA2 receptor that is highly expressed by
      several cancers. Peritoneal fluids were removed by paracentesis from the
      experimental group and mixed with the functionalized MNPs. Magnetic filtration
      was used to remove particle/malignant cell conjugates and filtered peritoneal
      fluids were re-introduced intraperitoneally. Control group II received the same
      treatment as the experimental group without MNPs. RESULTS: Experimental group
      tumor progression was 10.77-times slower than that of control group I.
      CONCLUSION: Reduction of malignant cell titer significantly prolonged time to end
      point in a metastatic ovarian cancer model.

PMID- 21182418
TI  - Transferrin-mediated targeting of bacteriophage HK97 nanoparticles into tumor
      cells.
AB  - AIMS: Next-generation targeted nanodevices are currently under development for
      imaging and therapeutic applications. We engineered HK97 viral nanoparticles
      (VNPs) for tumor cell-specific targeting. METHODS: A combination of genetic and
      chemical engineering methods were developed and applied to generate dual-labeled
      HK97 cysteine mutant particles displaying transferrin and fluorescent labels. The
      targeting properties of transferrin-conjugated VNPs were evaluated by in vitro
      experiments using different cancer cell lines. RESULTS: We found that HK97
      transferrin formulations were indeed targeted to cancer cells in vitro via the
      transferrin receptor. These studies highlight the utility and facilitate the
      further development of HK97-based VNPs.

PMID- 21182420
TI  - Epigallocatechin gallate-loaded polysaccharide nanoparticles for prostate cancer
      chemoprevention.
AB  - AIMS: Polysaccharide nanoparticles were studied as drug delivery vehicles for
      chemopreventive agents. MATERIALS & METHODS: Green tea polyphenol
      epigallocatechin-3-gallate (EGCG) was incorporated into a carbohydrate matrix of
      gum arabic and maltodextrin with an encapsulation efficiency of approximately
      85%. RESULTS: Encapsulated EGCG retained its biological activity, reducing the
      cell viability and inducing apoptosis of Du145 prostate cancer cells. Clonogenic
      assay demonstrated that encapsulation of EGCG enhanced its inhibitory effect on
      cell proliferation (10-20%) at lower concentrations (1-2 uM), compared with free
      EGCG. CONCLUSION: This study highlights the use of polysaccharide nanoparticles
      in chemoprevention as they can be used to deliver natural antioxidants capable of
      inhibiting steps of the tumorigenesis process.

PMID- 21182421
TI  - Efficient gene delivery by EGF-lipoplexes in vitro and in vivo.
AB  - AIMS: In this work, we have evaluated the ability of targeted lipoplexes to
      enhance transgene expression in EGF receptor (EGFR) overexpressing tumor cells by
      using lipoplexes. MATERIALS & METHODS: We prepared DOTAP/cholesterol liposomes
      modified with EGF at 0.5/1, 1/1, 2/1 and 5/1 lipid/DNA (+/-) charge ratio by
      sequentially mixing the liposomes with the ligand and adding the reporter or the
      therapeutic plasmid gene, pCMVLuc (pVR1216) or pCMVIL12, respectively. HepG2,
      DHDK12proB and SW620 cells were used for in vitro experiments, which were
      performed in the presence of 60% serum. RESULTS: The characterization of EGF
      lipoplexes indicated a size close to 300 nm and a variable net surface charge as
      a function of the amount of EGF associated to the cationic liposomes. EGF
      lipoplexes, which showed an increased transfection activity, were positively
      charged, noncytotoxic and highly effective in protecting DNA from DNase I attack.
      Transfection activity in vitro resulted in an enhancement in the luciferase and
      IL-12 expression by EGF-lipoplexes compared with those without ligand (plain
      lipoplexes) and to naked DNA. The results observed in SW620 cells, which are
      deficient in EGFR, confirmed that DNA uptake was predominantly via EGFR-mediated
      endocytosis. In vivo transfection activity was confirmed by luciferase imaging in
      living mice. Bioluminiscence could be detected mainly in the lung with a maximum
      signal 24 h after application. The resulting EGF-lipoplexes significantly
      increased the level of gene expression in mice compared with control or naked
      DNA. CONCLUSION: These findings indicate that these nanovectors may be an
      adequate alternative to viral vectors for gene therapy.

PMID- 21182422
TI  - Nanoparticles: heating tumors to death?
AB  - Thermotherapy consisting of heating tumors to death appears to be a suitable
      method to achieve tumor ablation in a noninvasive manner with minimal side
      effects but developments were hampered because of the lack of specificity of the
      heating method. New interests have emerged by introducing nanoparticles as energy
      absorbent agents in tumor tissue to locally enhance the action of irradiation,
      hence increasing the specificity of the method. Mechanisms of tumor death depend
      on the nature of the nanoparticles and irradiation modalities. They can be
      induced either by heat-dependent or by heat-independent phenomena. As discussed
      in this article, it can reasonably be expected that the recent methods of
      thermotherapy developed with nanoparticles have a tremendous potential for cancer
      treatments. However, overcoming challenging milestones is now required before the
      method will be ready for the treatment of a wide range of cancers.

PMID- 21182423
TI  - Emerging applications of multifunctional elastin-like recombinamers.
AB  - Elastin-like recombinamers have grown in popularity in the field of protein
      inspired biomimetic materials and have found widespread use in biomedical
      applications. Modern genetic-engineering techniques have allowed the design of
      multifunctional materials with an extraordinary control over their architecture
      and physicochemical properties, such as stimuli-responsiveness, monodispersity,
      biocompatibility or self-assembly, amongst others. Indeed, these materials are
      playing an increasingly important role in a diverse range of applications, such
      as drug delivery, tissue engineering and 'smart' systems. Herein, we review some
      of the most interesting examples of recent advances and progressive applications
      of elastin-like recombinamers in biomaterial and nano-engineering sciences in
      recent years.

PMID- 21182424
TI  - Nanocarriers for pulmonary administration of peptides and therapeutic proteins.
AB  - Peptides and therapeutic proteins have been the target of intense research and
      development in recent years by the pharmaceutical and biotechnology industry.
      Preferably, they are administered through the parenteral route, which is
      associated with reduced patient compliance. Formulations for noninvasive
      administration of peptides and therapeutic proteins are currently being
      developed. Among them, inhalation appears as a promising alternative for the
      administration of such products. Several formulations for pulmonary delivery are
      in various stages of development. Despite positive results, conventional
      formulations have some limitations such as reduced bioavailability and side
      effects. Nanocarriers may be an alternative way to overcome the problems of
      conventional formulations. Some nanocarrier-based formulations of peptides and
      therapeutic proteins are currently under development. The results obtained are
      promising, revealing the usefulness of these systems in the delivery of such
      drugs.

PMID- 21182425
TI  - Identifying the pulmonary hazard of high aspect ratio nanoparticles to enable
      their safety-by-design.
AB  - High aspect ratio, or fiber-shaped, nanoparticles (HARNs) represent a growth area
      in nanotechnology as their useful properties become more apparent. Carbon
      nanotubes, the best known and studied of the HARNs are handled on an increasingly
      large scale, with subsequent potential for human inhalation exposure. Their
      resemblance to asbestos fibers precipitated fears that they might show the same
      type of pathology as that caused by asbestos and there is emerging evidence to
      support this possibility. The large number of other HARNs, including nanorods,
      nanowires and other nanofibers, require similar toxicological scrutiny. In this
      article we describe the unusual hazard associated with fibers, with special
      reference to asbestos, and address the features of fibers that dictate their
      pathogenicity as developed in the fiber pathogenicity paradigm. This paradigm is
      a robust structure:toxicity model that identifies thin, long, biopersistent
      fibers as the effective dose for fiber-type pathogenic effects. It is likely that
      HARNs will in general conform to the paradigm and such an understanding of the
      features that make fibers pathogenic should enable us to design safer HARNs.

PMID- 21182426
TI  - Nanomaterials for regenerative medicine.
AB  - The application of nanotechnology has opened a new realm of advancement in the
      field of regenerative medicine and has provided hope for the culmination of long
      felt needs by the development of an ideal means to control the biochemical and
      mechanical microenvironment for successful cell delivery and tissue regeneration.
      Both top-down and bottom-up approaches have been widely used in the advancement
      of this field, be it by improvement in scaffolds for cell growth, development of
      new and efficient delivery devices, cellular modification and tracking
      applications or by development of nanodevices such as biosensors. The current
      review elaborates the various nanomaterials used in regenerative medicine with a
      special focus on the development of this field during the last 5 years and the
      recent advances in their aforementioned applications. Furthermore, the key issues
      and challenges in using nanotechnology-based approaches are highlighted with an
      outlook on the likely future of nano-assisted regenerative medicine.

PMID- 21182428
TI  - Injection site and pharmacokinetics after intravitreal injection of
      immunoglobulin G.
AB  - PURPOSE: The aim of this study was to investigate whether the pharmacokinetics
      differ after immunoglobulin G (IgG) intravitreal injections are done in the
      different sites of the vitreous cavity of rabbit eyes. METHODS: To examine the
      pharmacokinetics in the vitreous and the retina/choroid, fluorescein
      isothiocyanate-labeled IgG (5  MUg/50  MUL) was injected from the superior pars
      plana into the vitreous cavity of rabbit eyes. An original intravitreal injection
      guide was used to fix the tip of the injection needle, with the tip fixed in
      either the superior-anterior vitreous (superior group) or in the posterior
      vitreous (posterior group). At 1  h, 1, 4, and 7 days after injection, the eyes
      were enucleated and frozen. The vitreous was cut into superior, inferior, and
      posterior vitreous sections, whereas the retina/choroid was cut into superior,
      inferior, and posterior retina/choroid sections. The IgG concentrations in the
      vitreous and the retina/choroid sections were then determined. RESULTS: In the
      posterior vitreous, the IgG concentration in the posterior group was
      significantly higher than that in the superior group at 1  h after injection (P <
      0.05). However, 1 day after injection, no significant differences were noted
      between the 2 groups. At 4 days after injection, the drug was diffusely spread in
      both groups. In the posterior retina/choroid, the IgG concentration was
      essentially the same regardless of the injection site or the amount of time after
      injection. The IgG concentration in the superior retina/choroid was significantly
      higher in the superior group than in the posterior group at 1  h and 1 day after
      injection (P < 0.05). There were no differences noted between the 2 groups for
      the IgG concentrations in the 3 sections at 4 and 7 days after injection.
      CONCLUSIONS: Intravitreally injected IgG remains in the area of the injection,
      with more than 1 day required for it to spread diffusely within the vitreous. In
      the posterior retina/choroid, results suggested that the concentration of IgG may
      be equal regardless of the injection site. In the superior retina/choroid area
      that was near the site of the injection, the concentration of drug tended to be
      higher.

PMID- 21182427
TI  - Characterization of anti-HIV activity mediated by R88-APOBEC3G mutant fusion
      proteins in CD4+ T cells, peripheral blood mononuclear cells, and macrophages.
AB  - In this study, we characterized the anti-HIV activities of various R88-APOBEC3G
      (R88-A3G) mutant fusion proteins in which each A3G mutant was fused with a virus
      targeting polypeptide (R14-88, hereafter named R88) derived from HIV-1 Vpr. Our
      results show that the introduction of the deaminase-defective mutant E259Q into
      R88-A3G did not affect the virion incorporation of this mutant but blocked the
      protein's ability to inhibit HIV-1 infection. Our data also reveal that the
      antiviral effect of A3GY124A, a previously described A3G virus-packaging mutant,
      was completely rescued when the mutant was fused with R88. In an attempt to
      identify the most potent R88-A3G fusion proteins against HIV-1 infection, we
      introduced two Vif-binding mutants (D128K and P129A) into the R88-A3G fusion
      protein and showed that both R88-A3GD128K and R88-A3GP129A possessed very potent
      anti-HIV activity. When R88-A3GP129A was transduced into CD4(+) C8166 T cells,
      HIV-1 infection was completely abolished for at least 24 days. In an attempt to
      further test the anti-HIV effect of this mutant in primary human HIV susceptible
      cells, we introduced R88-A3GP129A into human peripheral blood mononuclear cells
      (PBMCs) and macrophages with a recombinant adeno-associated virus (rAAV2/5)
      vector. The results demonstrate that a significant inhibition of HIV-1 infection
      was observed in the transduced PBMCs and macrophages. These results provide
      evidence for the feasibility of an R88-A3G-based anti-HIV strategy. The further
      optimization of this system will contribute to the development of new anti-HIV
      gene therapy approaches.

PMID- 21182429
TI  - Pharmacokinetic features of difluprednate ophthalmic emulsion in rabbits as
      determined by glucocorticoid receptor-binding bioassay.
AB  - PURPOSE: Difluprednate (6alpha,9-difluoro-11beta,17,21-trihydroxy-1,4-pregnadiene
      3,20-dione 21-acetate 17-butyrate, DFBA) has long been used as an anti
      inflammatory dermatological agent. The main objectives of the current study were
      to evaluate the pharmacokinetic and pharmacodynamic features of DFBA when used as
      an ophthalmic agent, and to compare these features with those of other common
      ophthalmic agents, to determine which has the highest activity. METHODS: A
      glucocorticoid (GC) receptor-binding test was performed to evaluate GC receptor
      binding activity (GCRBA, the index of pharmacological effect). Using this
      information, we calculated dose-response curves, IC(50) values, and K(d) values
      to evaluate each drug's K(i) value. Finally, we performed studies in live rabbits
      to compare the activity of 4 formulations [0.002%, 0.01%, or 0.05% DFBA, or an
      ophthalmic solution of 0.1% betamethasone sodium phosphate (BMP)] at 4 time
      points (0.5, 1, 2, 4  h). At each time point, blood and eye samples were taken so
      that C(max) (the maximum equivalent concentration of the active DFBA metabolite,
      DFB), T(max) (the time at which C(max) was measured), and the area under the
      concentration-time curve could be compared across the 4 formulations. RESULTS:
      BMP had the highest K(i) value (8.4 * 10(-8) nmol/L), whereas DFB had the lowest
      (6.1 * 10(-11) nmol/L). The GCRBA of DFBA was intermediate to these 2 values (7.8
      * 10(-10) nmol/L). Instillation of the DFBA ophthalmic emulsion in the eyes of
      rabbits led to dose-dependent increases in GCRBA, which was mostly attributable
      to the activity of DFB. The 0.05% DFBA ophthalmic emulsion elicited the greatest
      response in both aqueous humor and iris/ciliary body tissues, though there were
      no significant dose-dependent differences in GCRBA in plasma samples.
      CONCLUSIONS: The 0.05% DFBA ophthalmic emulsion appears to be an effective and
      safe anti-inflammatory treatment in ocular tissues. It is comparable, and
      possibly even superior, to the 0.1% BMP solution, and may be particularly useful
      in cases of severe disease where treatment with BMP solution alone is
      insufficient.

PMID- 21182430
TI  - Phytochemical investigation and proximate analysis on the leaves of Cnidoscolus
      aconitifolius.
AB  - The study was designed to carry out the phytochemical screening and the proximate
      analysis of Cnidoscolus aconitifolius leaves. The results obtained showed the
      presence of tannins, saponin, alkaloids, and flavonoids with the absence of
      glycosides. The proximate analysis and mineral composition of C. aconitifolius
      leaves showed high levels of crude protein, ash, and fiber, in that order, and
      low fat content with concomitant presence of minerals such as sodium, manganese,
      magnesium, potassium, calcium, iron, phosphate, and zinc. The leaves of C.
      aconitifolius have high nutrient potentials and could be used as nutraceuticals
      in complementary foods, especially in sub-Saharan Africa.

PMID- 21182431
TI  - Managing bone health with zoledronic acid: a review of randomized clinical study
      results.
AB  - AIM: To systematically review randomized, controlled clinical trials for managing
      osteoporosis, cancer treatment-induced bone loss, and bone metastases from breast
      cancer using zoledronic acid (ZOL). METHOD: A systematic review of published
      literature and meeting abstracts was conducted to examine the efficacy of ZOL
      dosing strategies in clinical trials of osteoporosis, adjuvant therapy for breast
      cancer, and bone metastases from breast cancer. Bone resorption rates, tumor
      burden, skeletal health goals, and clinical data were considered when assessing
      ZOL in each setting. RESULTS: Dosing schedules vary between approved indications
      for osteoporosis and bone metastases and the investigational use in women
      receiving endocrine therapy for BC, taking into consideration the different
      levels of bone loss and tumor burden in each setting. Gradual bone loss in
      healthy postmenopausal women with osteopenia or osteoporosis can be prevented or
      treated with the approved biennial or annual ZOL (5 mg), respectively. Rapid bone
      loss in patients receiving adjuvant chemotherapy and/or endocrine therapy for
      early-stage BC and low tumor burden is managed in the clinical setting with ZOL 4
      mg every 6 months. In patients with bone metastases, very high tumor burden, high
      bone resorption levels, and decreases in bone integrity are managed by the
      approved ZOL schedule (4 mg every 3-4 weeks) to prevent skeleton-related events.
      CONCLUSIONS: Dosing schedules are based on clinical evidence and vary depending
      on goals of therapy, rate of bone loss, and tumor burden. ZOL 5 mg every 12
      months and every 24 months are approved for osteoporosis and osteopenia,
      respectively, whereas ZOL 4 mg every 6 months has been used during adjuvant
      endocrine therapy and ZOL 4 mg every 3-4 weeks is approved for managing bone
      metastases.

PMID- 21182432
TI  - Should we consider assessment of bone mineral density earlier in postmenopausal
      women with pelvic organ prolapse?
AB  - OBJECTIVE: To investigate a possible association between the presence of pelvic
      organ prolapse and osteopenia or osteoporosis in early postmenopausal women.
      DESIGN: Eighty-seven postmenopausal women between the ages of 55 and 60 years who
      had been admitted to the Gynecology or Menopause Outpatient clinics of Marmara
      University, School of Medicine were included in the study. Quantification of
      pelvic organ prolapse was performed for each patient. The bone mineral density
      measurements of the lumbar vertebrae by dual-energy X-ray absorptiometry were
      compared between the groups with and without pelvic organ prolapse. RESULTS: The
      mean T-scores for the lumbar area for women with or without pelvic organ prolapse
      were comparable between the study groups. CONCLUSIONS: It appears that presence
      of pelvic organ prolapse in early postmenopausal women is not helpful in
      predicting osteoporosis.

PMID- 21182433
TI  - Antigenotoxicity, cytotoxicity, and apoptosis induction by apigenin, bisabolol,
      and protocatechuic acid.
AB  - Medicinal plants represent an important resource in new drug research.
      Antioxidant properties of plants can help to scavenge reactive oxygen species.
      The objective of this work was to evaluate the genotoxic, antigenotoxic,
      tumoricidal, and apoptotic effect of some major phenols (apigenin, bisabolol, and
      protocatechuic acid) from two medicinal plants, Matricaria chamomilla and Uncaria
      tomentosa. The wing spot test of Drosophila melanogaster was used to evaluate the
      genotoxicity and antigenotoxicity of the three phenols. The human model of HL-60
      leukemia cells was used for the assessment of the cytotoxic effect, growth, and
      cellular viability. The apoptotic effect was evaluated using a DNA fragmentation
      assay based on the formation of internucleosomal units. Protocatechuic acid (0.25
      and 1 mM), apigenin (0.46 and 1.85 mM), and bisabolol (0.56 and 2.24 mM) did not
      exhibit any genotoxic effect. The three phenols showed an antigenotoxic effect
      against the hydrogen peroxide effect and also exhibited tumoricidal activity.
      Apigenin (2.24-35.96 mM) showed a lower 50% inhibitory concentration (0.75 and
      3.87 mM for the trypan blue test and WST-8 colorimetric assay, respectively) than
      bisabolol and protocatechuic acid. These phenolics also induced apoptosis in HL
      60 leukemia cells. This study suggests that the antioxidant activity of
      Chamomilla and Uncaria could be partially responsible of their beneficial
      activity.

PMID- 21182434
TI  - Development and pilot testing of the collaborative practice assessment tool.
AB  - Collaborative practice is receiving increased attention as a model of healthcare
      delivery that positively influences the effectiveness and efficiency of patient
      care while improving the work environment of healthcare providers. The
      collaborative practice assessment tool (CPAT) was developed from the literature
      to enable interprofessional teams to assess their collaborative practice. The
      CPAT survey included 56 items across nine domains including: mission and goals;
      relationships; leadership; role responsibilities and autonomy; communication;
      decision-making and conflict management; community linkages and coordination;
      perceived effectiveness and patient involvement; in addition to three open-ended
      questions. The tool was developed for use in a variety of settings involving a
      diversity of healthcare providers with the aim of helping teams to identify
      professional development needs and corresponding educational interventions. The
      results of two pilot tests indicated that the CPAT is a valid and reliable tool
      for assessing levels of collaborative practice within teams. This article
      describes the development of the tool, the pilot testing and validation process,
      as well as limitations of the tool.

PMID- 21182436
TI  - The role of nurse practitioners in hospital settings: implications for
      interprofessional practice.
AB  - Expansion of the nurse practitioner (NP) role worldwide indicates a need to
      understand how the role functions in interprofessional healthcare teams. Through
      the adoption of a mixed methods approach that gathered on-site tracking and
      observation, self-recorded logs of consultations and focus group interviews of
      team members and NPs, we describe the extent of role activity and the nature of
      interprofessional practices of 46 NPs and their team members in nine hospital
      sites across the province of Ontario, Canada. Findings outline the nature of the
      NP role activities, which largely focused on providing clinical care, with the
      support of their team, to a range of patients across the study settings. We
      discuss how 'embedding' the NP in this way appears to contribute to utilization
      of expertise of all professions as well as enabling team members to promote
      evidence-based practices. We argue that the use of NPs augments interprofessional
      role utilization through their desire to consult with a range of professionals
      and the capacity to perform holistic care for patients that is not limited to
      traditional nursing boundaries.

PMID- 21182437
TI  - Evaluating the effectiveness of an interprofessional education faculty
      development course: the transfer of interprofessional learning to the academic
      and clinical practice setting.

PMID- 21182438
TI  - Assessing female students' attitudes in various health and social professions
      toward working with people with autism: a preliminary study.
AB  - A range of professionals needs to work collaboratively in providing services for
      the growing numbers of people diagnosed with autism. Given the challenges of
      recruiting health professionals to work with people with disabilities in general,
      it is important to understand the factors that affect students' choices about
      working with people with autism, in particular. The aim of the present study was
      to assess attitudes of students in various health and social professions toward
      working with people with autism. An elicitation study based on the theory of
      planned behavior was conducted among 42 female students from the departments of
      social work, education, nursing, occupational therapy, and communication
      disorders/speech and language therapy. Working with people with autism was
      perceived as difficult, challenging, and frustrating, yet rewarding, important,
      and an opportunity to develop personally and professionally. Furthermore, the
      importance of awareness to stigmatic beliefs was raised. Familiarity, knowledge,
      and training were perceived as important. The results call for increasing
      university curriculum in the area of autism, increasing the contact of students
      with this population and focusing on training in interprofessional collaboration.

PMID- 21182439
TI  - A scoping review to improve conceptual clarity of interprofessional
      interventions.
AB  - Interprofessional education (IPE) and interprofessional collaboration (IPC) have
      been identified in health education and health care as playing an important role
      in improving health care services and patient outcomes. Despite a growth in the
      amount of research in these areas, poor conceptualizations of these
      interprofessional activities have persisted. Given the conceptual challenges, a
      scoping review of the interprofessional field was undertaken to map the
      literature available in order to identify key concepts, theories and sources of
      evidence. The objective of this review was to develop a theoretically based and
      empirically tested understanding of IPE and IPC. A total of 104 studies met the
      criteria and were included for analysis. Studies were examined for their approach
      to conceptualization, implementation, and assessment of their interprofessional
      interventions. Half of the studies were used for interprofessional framework
      development and half for framework testing and refinement. The final framework
      contains three main types of interprofessional interventions: IPE;
      interprofessional practice; and interprofessional organization; and describes the
      nature of each type of intervention by stage, participants, intervention type,
      interprofessional objectives, and outcomes. The outcomes are delineated as
      intermediate, patient, and system outcomes. There was very limited use of theory
      in the studies, and thus theoretical aspects could not be incorporated into the
      framework. This study offers an initial step in mapping out the interprofessional
      field and outlines possible ways forward for future research and practice.

PMID- 21182440
TI  - Translating collaborative knowledge into practice: findings from a 6-month follow
      up study.

PMID- 21182441
TI  - Developing core interprofessional competencies for community rehabilitation
      practitioners: findings from an Australian study.
AB  - This study aimed to determine the core competencies that underpin the practice of
      community rehabilitation (CR) practitioners working in a single state in
      Australia. Using a recursive and consultative methodology designed to build
      consensus, CR professionals, trainers, educators, and researchers developed a
      preliminary set of core interprofessional competencies that were considered
      essential to their practice. Data were collected in four main stages that engaged
      practitioners and experts in the CR field in the process of identifying,
      defining, validating, and endorsing a set of competencies. The first stage
      involved focus groups with 50 senior practitioners in metropolitan, rural/remote,
      regional, and indigenous communities. The second and third stages involved expert
      panels consisting of 20 trainers/educators, senior leaders, and scholars who
      refined, defined and validated the competency areas and developed statements that
      reflected the data.These statements formed the basis of a survey that was
      distributed to all current CR practitioners based in this state for endorsement,
      40 of whom responded. Ten competencies emerged from this process. Although there
      are limitations to the application of competencies, they will have significant
      implications for the future training of CR practitioners who can transcend
      professional boundaries.

PMID- 21182442
TI  - Interprofessional collaboration within integrative healthcare clinics through the
      lens of the relationship-centered care model.
AB  - Teamwork is a contemporary way to try to improve the healthcare system, not only
      for the patients but also for the practitioners involved. A new type of
      interprofessional working arrangement, integrative healthcare (IHC) clinics, has
      emerged in the last two decades. The literature on interprofessional
      collaboration is steadily increasing, but little is known about the collaborative
      organization of the biomedical and complementary and alternative medicine (CAM)
      practitioners that make up the teams in these clinics. The relationship-centered
      care model was used to guide an exploration of the interprofessional teamwork
      within a Canadian IHC setting. A sample of 31 IHC clinics and 228 biomedical and
      CAM practitioners were included. Eighty-nine questionnaires were returned from 25
      clinics, representing a 62% practitioner response rate (within clinic
      responders). This study established that within the analytical model,
      practitioners behaviors and skills are the main factors associated with job
      satisfaction and inter-practitioner conflicts in interprofessional IHC practice.
      The results of the study also suggested the importance of interprofessional
      exposure for healthcare practitioners who are being expected to serve a clientele
      that is increasingly interested in being both cured and healed by the integration
      of biomedical and CAM paradigms and approaches.

PMID- 21182443
TI  - An investigation of "agreement" in the context of interprofessional discussion
      online: a "netiquette" of interprofessional learning?
AB  - This article suggests that "agreement" is a predominant feature of online
      discussions amongst undergraduate health and social care professionals, which is
      an area of concern. The context for the research is an online interprofessional
      learning pathway completed by ~2,800 students each year. The concept of
      agreement, how and why it is reached and what it indicates in an online
      interprofessional group is examined. The underpinning educational rationale for
      instigating online interprofessional dialogue was the potential to provide a
      powerful interface for bringing together students across a wide range of
      professional groups, which is necessary to promote interprofessional learning.
      Discourse analysis was used to analyze digital texts of interaction in online
      forums. The discussion forum discourse shows evidence of increased
      interprofessional knowledge and understanding, as well as capacity for
      interprofessional dialogue. Discussions were largely characterized by agreement,
      although some disagreement was evident. These findings support previous research
      in online dialogue. However, they are interpreted in an interprofessional context
      as constituting a specific type of "netiquette" in relation to the participants
      and their identification with professional discourses and to the learning
      activities that shaped discussions. The research has significance for teachers,
      researchers, and practitioners involved in promoting interprofessional learning
      through online discussion forums.

PMID- 21182444
TI  - A critical examination of the role of appreciative inquiry within an
      interprofessional education initiative.
AB  - Appreciative inquiry (AI) is a relatively new approach to initiating or managing
      organizational change that is associated with the 'positiveness' movement in
      psychology and its offshoot positive organizational scholarship. Rather than
      dwelling upon problems related to change, AI encourages individuals to adopt a
      positive, constructive approach to managing change. In recent years, AI has been
      used to initiate change across a broad range of public and private sector
      organizations. In this article, we report findings from a subset of 50 interviews
      gathered in a wider study of interprofessional education (IPE) in which AI was
      employed as a change agent for implementing IPE in a number of health care
      institutions in a North American setting. A multiple case study approach. (Yin,
      2002) was employed in the wider study and semi-structured interviews were
      undertaken with participants both before their IPE programs and directly
      afterwards to obtain a detailed understanding of their expectations and
      experiences of IPE. Interviews were analyzed in an inductive thematic manner in
      order to produce key emergent themes from each of the IPE programs. A process of
      re-analysis provided a set of themes which offered an understanding of the role
      of AI within this IPE initiative. Our findings identify a strong resonance and
      fit for AI both among the health and social care professionals who participated
      in this initiative. Numerous individuals commented on the enthusiasm and energy
      AI engendered, while praising its ability to enhance their working lives and
      interprofessional relationships. Yet a number of difficulties were also reported.
      These focused on problems with the translation of the AI process into achievable
      structural level (e.g. professional, cultural) changes. Based on these findings,
      the article goes on to argue that the use of AI can overlook a number of
      structural factors, which will ultimately limit its ability to actually secure
      meaningful and lasting change within health care.

PMID- 21182446
TI  - Olive leaf extract facilitates healing of experimental cartilaginous injuries in
      rabbits.
AB  - We investigated the restorative effect of orally administered olive leaf extract
      (OLE) on experimentally produced cartilaginous injuries in rabbits. In total,
      three holes in the left stifle joint, including one in the medial trochlear ridge
      and two in the trochlear sulcus (proximal and distal) of articular cartilage,
      were prepared surgically using a drill. For the control group only tap water
      alone was administered daily, and for the OLE group a water-based solution of OLE
      (500 mg/kg/day) was administered daily. The injured areas were observed
      macroscopically and histologically at 3 weeks after the operation. The results
      indicate that OLE facilitated healing of the three holes and increased the weight
      of the biceps femoris muscle. Histological examination revealed that in the OLE
      group, matured cartilage tissues and connective tissues were mixed with
      regenerated or maturing cartilage tissues with massive proliferation in the
      injured parts, around which the proliferation of undifferentiated blast cells and
      the tissue with cartilage substrates were observed. The histological score of the
      OLE group was significantly lower than that of the control group. The percentage
      of proliferating cell nuclear antigen-positive cartilage cells in the OLE group
      was higher than in the control group. Mean density of the restored area observed
      with Safranin O staining was higher in the OLE group than in the control group.
      Therefore, OLE is effective for enhancing the healing of cartilaginous injuries.
      OLE may also have a beneficial effect of slowing and reducing the pathogenesis of
      degenerative joint diseases in humans.

PMID- 21182448
TI  - Use of 2-MUm continuous-wave thulium laser for surgical removal of a tentorial
      meningioma: case report.
AB  - BACKGROUND: Since the early 1980s, CO(2), neodymium-doped yttrium aluminum garnet
      (Nd:YAG), and other laser prototypes have been widely used in neurosurgery as an
      intraoperative aid along with the cavitron ultrasonic surgical aspirator (CUSA),
      bipolar forceps, and microdissection. However, the English literature contains
      almost no reports on the use of thulium lasers during neurosurgical procedures.
      METHODS: We report our experience with a thulium laser during the surgical
      removal of a tentorial meningioma. The intraoperative technique utilized, as well
      as the clinical and radiological results of the procedure, are described.
      RESULTS: The thulium laser proved to be a useful tool during coagulation,
      shrinking, and resection of the basal implant of the tumor. Use of the laser made
      the surgical procedure faster and easier, and no intraoperative bleeding was
      noted. No side effects were observed. CONCLUSIONS: Our experience indicates that
      thulium lasers are a valid aid during resection of benign intracranial tumors
      under microscope magnification. Additional studies are required to define fully
      the role of these lasers in neurosurgical procedures.

PMID- 21182447
TI  - Improved cognitive function after transcranial, light-emitting diode treatments
      in chronic, traumatic brain injury: two case reports.
AB  - OBJECTIVE: Two chronic, traumatic brain injury (TBI) cases, where cognition
      improved following treatment with red and near-infrared light-emitting diodes
      (LEDs), applied transcranially to forehead and scalp areas, are presented.
      BACKGROUND: Significant benefits have been reported following application of
      transcranial, low-level laser therapy (LLLT) to humans with acute stroke and mice
      with acute TBI. These are the first case reports documenting improved cognitive
      function in chronic, TBI patients treated with transcranial LED. METHODS:
      Treatments were applied bilaterally and to midline sagittal areas using LED
      cluster heads [2.1" diameter, 61 diodes (9 * 633 nm, 52 * 870 nm); 12-15 mW per
      diode; total power: 500 mW; 22.2 mW/cm(2); 13.3 J/cm(2) at scalp (estimated 0.4
      J/cm(2) to cortex)]. RESULTS: Seven years after closed-head TBI from a motor
      vehicle accident, Patient 1 began transcranial LED treatments. Pre-LED, her
      ability for sustained attention (computer work) lasted 20 min. After eight weekly
      LED treatments, her sustained attention time increased to 3 h. The patient
      performs nightly home treatments (5 years); if she stops treating for more than 2
      weeks, she regresses. Patient 2 had a history of closed-head trauma
      (sports/military, and recent fall), and magnetic resonance imaging showed
      frontoparietal atrophy. Pre-LED, she was on medical disability for 5 months.
      After 4 months of nightly LED treatments at home, medical disability
      discontinued; she returned to working full-time as an executive consultant with
      an international technology consulting firm. Neuropsychological testing after 9
      months of transcranial LED indicated significant improvement (+1, +2SD) in
      executive function (inhibition, inhibition accuracy) and memory, as well as
      reduction in post-traumatic stress disorder. If she stops treating for more than
      1 week, she regresses. At the time of this report, both patients are continuing
      treatment. CONCLUSIONS: Transcranial LED may improve cognition, reduce costs in
      TBI treatment, and be applied at home. Controlled studies are warranted.

PMID- 21182449
TI  - Effect of photobiomodulation on vinblastine-poisoned murine HERS cells.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of near-infrared
      (NIR) photobiomodulation on the proliferation and glutathione levels in murine
      Hertwig's epithelial root sheath (HERS) cells after poisoning with vinblastine.
      BACKGROUND: Photobiomodulation has been shown to improve wound healing in a
      number of animal models. There have been no studies on the effect of
      photobiomodulation on cancer-related chemotherapy injury to the cells that
      initiate tooth root growth. MATERIALS AND METHODS: Control groups consisted of
      murine HERS cells without vinblastine (VB-) and cells with vinblastine at 10, 20,
      and 30 ng/mL (VB10, VB20, and VB30). Experimental groups consisted of these same
      groups with light therapy (VB-L, VB10L, VB20L, and VB30L). The cells were exposed
      to vinblastine for 1 h. Photobiomodulation consisted of a 75-cm(2) gallium
      aluminum-arsenide light-emitting diode (LED) array at an energy density of 12.8
      J/cm(2), delivered with 50 mW/cm(2) power over 256 s. RESULTS: Vinblastine alone
      significantly decreased HERS cell proliferation and glutathione levels at all
      concentrations (VB10 [-55%, p < 1.0 * 10(-8)]; VB20 [-72%, p < 1.0 * 10(-9)];
      VB30 [-80%, p < 1.0 * 10(-10)]; and VB10 [-36%, p < 0.0001]; VB20 [-49%, p < 1.0
      * 10(-6)]; VB30 [-53%, p < 1.0 * 10(-7)] respectively). Photobiomodulation
      significantly increased cell proliferation at all levels of vinblastine exposure
      (VB10L [+50%, p < 0.0001]; VB20L [+45%, p < 0.05]; VB30 [+39%, p < 0.05]) but not
      of the control (+22%, p = 0.063). The photobiomodulation significantly increased
      glutathione production in all concentrations of vinblastine except 20 ng/mL
      (VB10L [+39%, p = 0.007]; VB20L [+19%, p = 0.087]; VB30 [+14%, p = 0.025]) and
      the control (+12%, p = 0.13). CONCLUSIONS: Photobiomodulation demonstrated an
      improvement in proliferation and glutathione levels in vinblastine-poisoned
      murine HERS cells.

PMID- 21182450
TI  - Laser-generated shockwave for clearing medical device biofilms.
AB  - OBJECTIVE: This study aimed to evaluate a laser method of biofilm interruption
      from the surface of various common medical devices and from surgically removed
      sinus tissue with adherent biofilms in a timely manner. BACKGROUND: Biofilm has
      emerged as a new threat not amenable to most antibiotic treatments. Biofilms, as
      opposed to planktonic bacteria, develop an extracellular polymeric slime matrix
      to facilitate adherence to host tissue or a prosthetic surface and to form a
      protective shield. A laser-induced biofilms disruption concept was previously
      described. MATERIALS AND METHODS: Biofilms were grown in the laboratory on
      metallic and plastic medical device surfaces such as stents. Attempts to remove
      the biofilms with a laser were undertaken three times for each device. Q-switched
      Nd:YAG laser-generated shockwaves affecting Pseudomonas aeruginosa biofilms
      expressing yellow fluorescent protein (YFP) biofilm coating were applied with
      biologically safe parameters utilizing a fiber delivery system and a special
      probe. A confocal microscope was used to identify the biofilm structure prior to,
      during, and after laser application. The amount of biofilm removed from the
      medical devices in time was measured by quantifying green fluorescence. RESULTS:
      The biofilm fluctuated and eventually broke off the surface as shock waves neared
      the target. The time to remove 97.9 +/- 0.4% (mean +/- 1SD, n = 3) the biofilm
      from the surface of a Nitinol (NiTi) stent ranged from 4 to 10 s. The detached
      biofilm was observed floating in fluid media in various microscopic size
      particles. CONCLUSIONS: A new treatment modality using laser-generated shockwaves
      in the warfare against biofilms growing on surgical devices was demonstrated. Q
      switched laser pulses stripped biofilm from the surface it adhered to, changing
      the bacteria to their planktonic form, making them amenable to conventional
      treatment. This therapeutic modality appears to be rapid, effective, and safe on
      metallic and plastic medical device surfaces.

PMID- 21182451
TI  - Carbon assisted Q-switched Nd:YAG laser treatment with two different sets of
      pulse width parameters offers a useful treatment modality for severe inflammatory
      acne: a case report.
AB  - BACKGROUND AND AIMS: The treatment of inflammatory and noninflammatory acne still
      presents problems to patients and dermatologists. A new technique using two
      different sets of 1064 nm Nd:YAG laser parameters has been developed in
      combination with a topical carbon lotion. A preliminary test of the efficacy of
      this new treatment technique is reported. SUBJECT AND METHODS: A 14-y-old girl
      presented with moderate to severe pustular and cystic acne over the bilateral
      cheeks and chin. Following topical local anesthesia, a topical carbon lotion was
      applied to the face, and a Q-switched frequency-doubled Nd:YAG laser was used
      first in a quasi-long pulsed mode (a 300-MUs pulse width at 1.1-1.5 J/cm(2))
      followed immediately by a Q-switched mode (5-nsec pulse width, 1.5-2.0 J/cm(2))
      using a 7-mm handpiece for both modes. Six treatments were given, 2 weeks apart.
      RESULTS: The procedure was well-tolerated. By the fourth treatment significant
      improvement was observed, and by the sixth treatment, better than 90% clearance
      of inflammatory lesions was achieved. At the 8-week follow-up after the last
      treatment, long-lasting improvements in the patient's acne were noted.
      Improvement was also noted in closed comedones and in the general skin condition,
      especially pores, sebum reduction, and the red spots seen after inflammatory
      acne. The patient was satisfied with the result. CONCLUSIONS: This new, minimally
      invasive technique as a stand-alone treatment gave very good clearance of
      inflammatory acne with minimal patient down time. Marked reduction in active acne
      was observed during treatments and at the 2-month follow-up visit. Further
      improvement could probably be achieved with other adjunctive therapeutic
      modalities.

PMID- 21182452
TI  - Effects of different swimming exercise intensities on bone tissue composition in
      mice: a Raman spectroscopy study.
AB  - OBJECTIVE: Raman spectroscopy was employed to evaluate the effect of different
      swimming intensities on femoral bone composition in an animal model. BACKGROUND
      DATA: Intense swimming exercise may affect bone mineralization, and Raman
      technique has been shown to be effective in evaluating tissue composition
      (phosphate minerals and carbonate apatites - bands at 960 and 1170 cm(-1), as
      well as collagen matrix - amide I band at 1660 cm(-1)). MATERIALS AND METHODS:
      Eighteen female Swiss Webster mice were separated into three groups (n = 6 per
      group) of sedentary (SED), and swimming with an intensity of 40% (PT-40) and 80%
      (PT-80) of the maximum load, with 6 weeks of training. Near-infrared Raman
      spectra (830 nm wavelength and 80 mW laser power) were obtained with a dispersive
      Raman spectrometer using a CCD camera and imaging spectrograph with 30-s
      integration time. Spectra were collected in the medial and lateral diaphysis of
      the femur and principal components analysis (PCA) was employed to extract
      features of the Raman bands of bone and to perform quantitative analysis.
      RESULTS: PC1 vector resembles Raman spectra and carries information about apatite
      minerals and some contribution from organic matrix. A statistically significant
      difference was found in the PC1 scores (ANOVA, p < 0.05), indicating lower
      mineral concentrations in the femur in both the PT-40 and PT-80 groups compared
      to the SED group. These results corroborated with the radiographic assessment of
      bone density. CONCLUSION: Raman technique associated with PCA statistics showed
      that intense swimming exercise may affect bone mineralization and remodeling in a
      mouse model of training.

PMID- 21182453
TI  - The RevoLix 2 micron continuous wave laser vaporesection for the treatment of
      high-risk patients with benign prostatic hyperplasia.
AB  - OBJECTIVE: To evaluate the safety and efficacy of the RevoLix 70W 2 micron
      continuous wave laser vaporesection in the treatment of high-risk patients with
      benign prostatic hyperplasia (BPH). BACKGROUND DATA: Forty-six high-risk patients
      (mean age, 82.6 y old) with BPH underwent 2-MUm continuous wave laser
      vaporesection. MATERIALS AND METHODS: The operative time, drop in hemoglobin,
      drop in serum sodium, indwelling catheterization time, operative complications,
      international prostatic symptom scores (IPSS), quality of life (QoL), urinary
      flow rate (Qmax), and post voiding residual urine volume (PVR) were observed.
      RESULTS: All 46 patients recovered without incident. The mean operative time was
      68 +/- 16.3 min. Occasional venous hemorrhage occurred during the operation, but
      no arterial hemorrhage was observed. Hemoglobin decreased from preoperative 15.0
      g/dL to postoperative 14.3 g/dL, serum sodium decreased from preoperative 142.4
      mmol/L to postoperative 141.6 mmol/L. IPSS decreased from preoperative 22 +/- 6.2
      to postoperative 9 +/- 3.3, QoL scores decreased from 5.1 +/- 0.7 to 2.1 +/- 0.7,
      Qmax increased from 8.4 +/- 5.2 to 21.2 +/- 12.3 mL/sec, PVR decreased from 94.2
      +/- 60.2 to 21.6 +/- 6.4 mL. The parameters were significantly different between
      pre- and postoperative results. CONCLUSIONS: The RevoLix 70W 2-MUm continuous
      wave laser vaporesection is safe and effective in the treatment of high-risk
      patients with BPH.

PMID- 21182454
TI  - Monitoring of native fluorescence induced by a glucose diet in Wistar rats.
AB  - OBJECTIVE: To investigate red fluorescence found in the digestive tract of Wistar
      rats submitted to stress produced by a liquid diet of 5% glucose and maintenance
      in darkness. BACKGROUND DATA: Protoporphyrin IX (PpIX) is produced by the
      Harderian gland, located in the inner corner of the eyes of rats. Under stressful
      conditions this gland increases the production of PpIX, which can be detected in
      different regions of the body, in a manner reminiscent of a porphyria. MATERIAL
      AND METHODS: Sixty-five Wistar rats were used in this study. The fluorescence
      spectra were registered with optical resolution better than 1.7 nm. The rats were
      fed a 5% glucose diet, exclusively, up to 120 h. The animals were evaluated
      throughout the diet period, which included two sequential experiments:
      considering the red fluorescence of their intestinal tract and the fluorescence
      that appeared in some external parts of their bodies (paw, tail, nose, and
      scrotum). The normal diet was reintroduced and new spectra were obtained after 24
      and 48 h. RESULTS: Experiment I showed a marked, time-dependent increase in the
      intestinal content of porphyrin in rats fed the glucose diet. The fluorescence
      spectrum of the material identified it as PpIX. The spectra collected in
      Experiment II showed an increase in fluorescence in the four external areas
      associated with the duration of the diet. This fluorescence disappeared after
      reintroduction of the regular diet. CONCLUSION: The feeding of a restricted diet
      (5% glucose) to Wistar rats resulted in reversible porphyria. Measurement of the
      fluorescence intensity may be a reliable method for monitoring the porphyrin
      content of tissues.

PMID- 21182456
TI  - Validation of a high-content screening assay using whole-well imaging of
      transformed phenotypes.
AB  - Automated microscopy was introduced two decades ago and has become an integral
      part of the discovery process as a high-content screening platform with
      noticeable challenges in executing cell-based assays. It would be of interest to
      use it to screen for reversers of a transformed cell phenotype. In this report,
      we present data obtained from an optimized assay that identifies compounds that
      reverse a transformed phenotype induced in NIH-3T3 cells by expressing a novel
      oncogene, KP, resulting from fusion between platelet derived growth factor
      receptor alpha (PDGFRalpha) and kinase insert domain receptor (KDR), that was
      identified in human glioblastoma. Initial image acquisitions using multiple tiles
      per well were found to be insufficient as to accurately image and quantify the
      clusters; whole-well imaging, performed on the IN Cell Analyzer 2000, while still
      two-dimensional imaging, was found to accurately image and quantify clusters, due
      largely to the inherent variability of their size and well location. The
      resulting assay exhibited a Z' value of 0.79 and a signal-to-noise ratio of 15,
      and it was validated against known effectors and shown to identify only
      PDGFRalpha inhibitors, and then tested in a pilot screen against a library of 58
      known inhibitors identifying mostly PDGFRalpha inhibitors as reversers of the KP
      induced transformed phenotype. In conclusion, our optimized and validated assay
      using whole-well imaging is robust and sensitive in identifying compounds that
      reverse the transformed phenotype induced by KP with a broader applicability to
      other cell-based assays that are challenging in HTS against chemical and RNAi
      libraries.

PMID- 21182457
TI  - Adjunct oral immunotherapy in patients with re-treated, multidrug-resistant or
      HIV-coinfected TB.
AB  - This Phase IIb, placebo-controlled study involved 55 TB patients treated with
      anti-TB therapy. They were divided into two groups, matched by age, gender,
      baseline bodyweight and clinical manifestations: one group (n = 27) received a
      once-daily V-5 Immunitor (V5) immunotherapy pill and the other (n = 28) received
      placebo. Only one (3.7%) and three (10.7%) subjects in V5 and placebo arms,
      respectively had first-diagnosed, drug-sensitive TB; the remaining patients had
      re-treated TB, multidrug-resistant TB or HIV-TB coinfection. After 1 month, 26
      out of 27 patients (96.3%) became sputum smear negative in the V5 group (p <
      0.0000001), whereas seven out of 28 (25%) in the placebo group had converted (p =
      0.005). V5 contributed to the downregulation of TB-associated inflammation, as
      shown by normalization of high leukocyte counts, erythrocyte sedimentation rate
      and faster defervescence than controls. Patients in both arms experienced an
      increase in the levels of hemoglobin corresponding to 128.9 +/- 17.6 versus 133.1
      +/- 14.7 g/l (p = 0.03) and 112.6 +/- 14 versus 117 +/- 11.7 g/l (p = 0.03) in V5
      and placebo arms, respectively. In total, 19 out of 28 placebo patients (67.9%)
      gained, on average, 1.07 kg (59.1 +/- 10 vs 60.1 +/- 10.4 kg; p = 0.003). By
      contrast, all patients in the V5 group gained weight with mean 3.4 kg (59.7 +/- 8
      vs 63.1 +/- 9 kg; p = 5.7E-007). Clinical symptoms improved among all patients in
      V5 arm, while 28.6% of patients on placebo reported satisfactory results (p =
      0.007). No adverse or side effects attributable to V5 were seen at any time.
      Further studies are needed to gauge the extent of the benefits of V5 as safe and
      effective adjunct immunotherapy for TB.

PMID- 21182458
TI  - A greater prevalence of X4 viruses in HIV type 1 intravenous drug users reflects
      a "CD4+ effect".

PMID- 21182455
TI  - Cell-specific aptamer-mediated targeted drug delivery.
AB  - Nucleic acid aptamers are in vitro-selected small, single-stranded DNA or RNA
      oligonucleotides that can specifically recognize their target on the basis of
      their unique 3-dimensional structures. Recent advances in the development of
      escort aptamers to deliver and enhance the efficacy of other therapeutic agents
      have drawn enthusiasm in exploiting cell-type-specific aptamers as drug delivery
      vehicles. This review mainly focuses on the recent developments of aptamer
      mediated targeted delivery systems. We also place particular emphasis on aptamers
      evolved against cell membrane receptors and possibilities for translation to
      clinical applications.

PMID- 21182459
TI  - Adaptive gene regulation of pyruvate dehydrogenase kinase isoenzyme 4 in
      hepatotoxic chemical-induced liver injury and its stimulatory potential for DNA
      repair and cell proliferation.
AB  - The processes involved in the adaptation of animals to environmental factors
      remain unclear. We examined the mechanisms underlying the adaptive potential of
      the mouse against hepatotoxic chemical-induced injury. Microarray analysis
      revealed that ethylbenzene, a hepatotoxic chemical, upregulated PDK4 (encoding
      pyruvate dehydrogenase kinase isoenzyme 4) in mouse livers and that the
      upregulation was enhanced by previous exposure to the chemical. Although PDK4 is
      an energy resource regulator induced by starvation, expression of other fasting
      inducible genes was unaffected. PDK4 induced by chemical stress developed hepatic
      accumulation of sirtuin 1 by regulating pyruvate concentration and activated the
      Nbn and ATM, which are critical for DNA repair and checkpoint activation. PDK4
      overexpression on carbon tetrachloride (CCl(4))-induced liver injury resulted in
      delayed necrotic tissue recovery with cell cycle arrest and decreased gammaH2AX
      foci and micronucleus formation. PDK4 silencing on CCl(4)-induced liver injury
      accelerated necrotic tissue recovery and increased gammaH2AX foci and
      micronucleus formation, indicating the essential role of PDK4 in DNA repair and
      checkpoint activation. PDK4 overexpression induced pancreas-specific
      transcription factor 1a (Ptf1a) upregulation and transcriptional activation of
      several pancreatic genes in the liver. Ptf1a overexpression by adenoviral gene
      delivery resulted in accelerated tissue recovery on CCl(4)-induced liver injury.
      Our data identified PDK4 as a novel pivotal factor in adaptation to chemical
      stress.

PMID- 21182461
TI  - Antiretroviral therapy-associated diseases are common in the long-term.

PMID- 21182462
TI  - Targeted delivery of a proapoptotic peptide to tumors in vivo.
AB  - RGD peptides recognize the alpha(v)beta(3) integrin, a receptor that is
      overexpressed on the surface of both tumor blood vessels and cancerous cells.
      These peptides are powerful tools that act as single antiangiogenic molecules,
      but recently also have been used for tumor imaging and drug targeting. We
      designed the molecule RAFT-(c[-RGDfK-])(4), a constrained and chemically defined
      entity that can be produced at clinical-grade quality. This scaffold was
      covalently coupled via a labile bridge to the proapoptotic peptide (KLAKLAK)(2)
      (RAFT-RGD-KLA). A fluorescent, activatable probe was also introduced, allowing
      intracellular localization. At 2.5 uM, this molecule induced the intracellular
      release of an active KLA peptide, which in turn caused mitochondrial
      depolarization and cell death in vitro in tumor cells. In a mouse model, the RAFT
      RGD-KLA peptide was found to prevent the growth of remote subcutaneous tumors.
      This study demonstrated that the antitumor peptide is capable of killing tumor
      cells in an RGD-dependent manner, thus lowering the nonspecific cytotoxic effects
      expected to occur when using cationic cytotoxic peptides. Thus, this chemistry is
      suitable for the design of complex, multifunctional molecules that can be used
      for both imaging and therapeutics, representing the next generation of perfectly
      controlled, targeted drug-delivery systems.

PMID- 21182463
TI  - Layer-by-layer self-assembly vectors for gene delivery.
AB  - The success of gene therapy largely relies on the development of high-efficient
      and low-toxic gene delivery vectors. Nanovector-based delivery of nucleic acids
      is a very promising approach for the effective transfer of genetic materials into
      cells. Compared with encapsulating of nucleic acids inside biodegradable
      nanoparticles which often suffers from low encapsulation efficiency and
      degradation of the loaded therapeutic gene, the layer-by-layer self-assembly
      vectors prepared by the surface adsorption of gene/polycation multilayered films
      on colloidal particles using layer-by-layer technique are a potent gene delivery
      system in offering efficient loading of nucleic acids, controlling the release of
      the loaded gene in physiological environment and targeting to a particular site
      or a specific cell type in the body. This review focuses on the preparation,
      advantages, application and the probable associated drawbacks of layer-by-layer
      self-assembly vectors for gene delivery.

PMID- 21182464
TI  - Non-viral gene delivery to mesenchymal stem cells: methods, strategies and
      application in bone tissue engineering and regeneration.
AB  - Mesenchymal stem cells (MSCs) can be isolated from several tissues in the body,
      have the ability to self-renewal, show immune suppressive properties and are
      multipotent, being able to generate various cell types. At present, due to their
      intrinsic characteristics, MSCs are considered very promising in the area of
      tissue engineering and regenerative medicine. In this context, genetic
      modification can be a powerful tool to control the behavior and fate of these
      cells and be used in the design of new cellular therapies. Viral systems are very
      effective in the introduction of exogenous genes inside MSCs. However, the risks
      associated with their use are leading to an increasing search for non-viral
      approaches to attain the same purpose, even if MSCs have been shown to be more
      difficult to transfect in this way. In the past few years, progress was made in
      the development of chemical and physical methods for non-viral gene delivery.
      Herein, an overview of the application of those methods specifically to MSCs is
      given and their use in tissue engineering and regenerative medicine therapeutic
      strategies highlighted using the example of bone tissue. Key issues and future
      directions in non-viral gene delivery to MSCs are also critically addressed.

PMID- 21182465
TI  - Artificial restriction DNA cutters to promote homologous recombination in human
      cells.
AB  - Homologous recombination is almost the only way to modify the genome in a
      predetermined fashion, despite its quite low frequency in mammalian cells. It has
      been already reported that the frequency of this biological process can be
      notably increased by inducing a double strand break (DSB) at target site. This
      article presents completely chemistry-based artificial restriction DNA cutter
      (ARCUT) for the promotion of homologous recombination in human cells. This cutter
      is composed of Ce(IV)/EDTA complex (molecular scissors) and two strands of
      peptide nucleic acid (PNA), and contains no proteins. Its scission site in the
      genome is determined simply by Watson-Crick rule so that ARCUT for desired
      homologous recombination is easily and straightforwardly designed and
      synthesized. The site-specificity of the scission is high enough to cut human
      genome at one target site. The DSB induced by this cutter is satisfactorily
      recognized by the repair system in human cells and promotes the targeted
      homologous recombination.

PMID- 21182467
TI  - Zinc-finger nuclease based genome surgery: it's all about specificity.
AB  - Therapeutic genome engineering is a hallmark of gene therapy but only recent
      technological advances have permitted the modification of complex genomes in a
      targeted fashion. Zinc-finger nucleases (ZFNs) have developed into a major
      playmaker in the genome engineering field and have been employed to trigger the
      targeted editing of genomes at over 50 gene loci in 11 model organisms, including
      fruitfly, zebrafish and rat, with allelic frequencies reaching the double digit
      percentage range. Moreover, ZFN-mediated genome surgery in primary human cells
      has become a reality and two phase I clinical trials aiming at knocking out the
      CCR5 receptor in T cells isolated from HIV patients to protect these cells from
      infection with the virus have been initiated. Considering that specificity is
      closely linked to ZFN activity and ZFN-associated toxicity, this parameter has
      been and will be a key quality in any therapeutic application of the designer
      nucleases. This review summarizes the technological innovations that have
      successfully catapulted ZFNs into the genome engineering arena and provides an
      overview of the current state of the art of these nucleases with reference to
      human gene therapy.

PMID- 21182468
TI  - Zinc-finger nucleases: a panoramic view.
AB  - Zinc-finger nucleases (ZFNs) are emerging as very powerful tools for directed
      genome modifications. Their key features are: a DNA-binding domain comprised of
      zinc fingers that can be designed to favor very specific targets; a nonspecific
      cleavage domain that must dimerize to cut DNA--this requirement enhances
      specificity and minimizes random cleavage. ZFNs have been shown to be effective
      in a wide range of organisms and cell types. This article reviews discoveries
      that led to the development of ZFNs, cites examples of successes in genome
      engineering, and projects how ZFNs may be used in the future, particularly in
      applications to humans.

PMID- 21182469
TI  - Pharmacogenomics of human ABC transporter ABCC11 (MRP8): potential risk of breast
      cancer and chemotherapy failure.
AB  - Some genetic polymorphisms of human ABC transporter genes are reportedly related
      to the risk of certain diseases and patients' responses to medication. Human
      ABCC11 functions as an ATP-dependent efflux pump for amphipathic anions. One non
      synonymous SNP 538G>A (Gly180Arg) has been found to greatly affect the function
      and stability of de novo synthesized ABCC11 (Arg180) variant protein. The SNP
      variant lacking N-linked glycosylation is recognized as a misfolded protein in
      the endoplasmic reticulum (ER) and readily undergoes proteasomal degradation.
      This ER-associated degradation of ABCC11 protein underlies the molecular
      mechanism of affecting the function of apocrine glands. On the other hand, the
      wild type (Gly180) of ABCC11 is associated with wet-type earwax, axillary
      osmidrosis, colostrum secretion from the mammary gland, and the potential
      susceptibility of breast cancer. Furthermore, the wild type of ABCC11 reportedly
      has ability to efflux cyclic nucleotides and nucleoside-based anticancer drugs.
      The SNP (538G>A) of the ABCC11 gene is suggested to be a clinical biomarker for
      prediction of chemotherapeutic efficacy. Major obstacle to the successful
      chemotherapy of human cancer is development of resistance, and nucleoside-based
      chemotherapy is often characterized by inter-individual variability. This review
      provides an overview about the discovery and the genetic polymorphisms in human
      ABCC11. Furthermore we focus on the impact of ABCC11 538G>A on the apocrine
      phenotype, patients' response to nucleoside-based chemotherapy, and the potential
      risk of breast cancer.

PMID- 21182470
TI  - Mechanisms of drug resistance to vascular endothelial growth factor (VEGF)
      inhibitors.
AB  - Angiogenesis inhibitors have a major role in the treatment of varying cancers
      today. While originally thought to be independent of resistance, increasing data
      suggests varying mechanisms that bring about drug resistance, either
      intrinsically or through adaptation. The role of vascular endothelial growth
      factor single nucleotide polymorphisms (VEGF SNPs) in terms of therapeutic
      response and toxicity has increasingly been recognized, as well as its potential
      for contributing to drug resistance. This review will focus on theories,
      preclinical models, and clinical trials that help elucidate the mechanisms of
      resistance and clinical response to angiogenesis inhibitors.

PMID- 21182466
TI  - Meganucleases and other tools for targeted genome engineering: perspectives and
      challenges for gene therapy.
AB  - The importance of safer approaches for gene therapy has been underscored by a
      series of severe adverse events (SAEs) observed in patients involved in clinical
      trials for Severe Combined Immune Deficiency Disease (SCID) and Chromic
      Granulomatous Disease (CGD). While a new generation of viral vectors is in the
      process of replacing the classical gamma-retrovirus-based approach, a number of
      strategies have emerged based on non-viral vectorization and/or targeted
      insertion aimed at achieving safer gene transfer. Currently, these methods
      display lower efficacies than viral transduction although many of them can yield
      more than 1% of engineered cells in vitro. Nuclease-based approaches, wherein an
      endonuclease is used to trigger site-specific genome editing, can significantly
      increase the percentage of targeted cells. These methods therefore provide a real
      alternative to classical gene transfer as well as gene editing. However, the
      first endonuclease to be in clinic today is not used for gene transfer, but to
      inactivate a gene (CCR5) required for HIV infection. Here, we review these
      alternative approaches, with a special emphasis on meganucleases, a family of
      naturally occurring rare-cutting endonucleases, and speculate on their current
      and future potential.

PMID- 21182471
TI  - Superoxide dismutases: anti- versus pro- oxidants?
AB  - The family of superoxide dismutases (SODs) are well known for their antioxidant
      actions exerted by catalyzing the conversion of O(2)(.-) into H(2)O(2) plus
      oxygen. The importance of this action is revealed by the multiple phenotypic
      deficits exhibited by a variety of organisms that have been made to lack one or
      more of the SODs. Never the less there have been reports of deleterious
      consequences caused by overproduction of SOD. Several explanations have been
      proposed for these counter intuitive effects; one of which is that elevated SOD
      causes increased formation of H(2)O(2). The reasons for dismissing this
      explanation are explored.

PMID- 21182472
TI  - FK506 binding proteins as targets in anticancer therapy.
AB  - FK506 binding proteins (FKBPs) are the intracellular ligands of FK506 and
      rapamycin, two natural compounds with powerful and clinically efficient
      immunosuppressive activity. In recent decades, a relevant role for
      immunosuppressants as anticancer agents has emerged. Especially, rapamycin and
      its derivatives are used, with successful results, across a variety of tumors. Of
      note, rapamycin and FK506 bind to FKBP12, and the resulting complexes interfere
      with distinct intracellular signaling pathways driven, respectively, by the
      mammalian target of rapamycin and calcineurin phosphatase. These pathways are
      related to T-cell activation and growth. Hyperactivation of the mammalian target
      of rapamycin (mTOR), particularly in cancers that have lost the tumor suppressor
      gene PTEN, plays an important pathogenetic role in tumor transformation and
      growth. The signaling pathway involving calcineurin and nuclear factors of
      activated T-lymphocytes is also involved in the pathogenesis of different cancer
      types and in tumor metastasis, providing a rationale for use of FK506 in
      anticancer therapy. Recent studies have focused on FKBPs in apoptosis regulation:
      Targeting of FKBP12 promotes apoptosis in chronic lymphocytic leukemia, FKBP38
      knockdown sensitizes hepatoma cells to apoptosis, and FKBP51 silencing overcomes
      resistance to apoptosis in acute lymphoblastic leukemia, prostate cancer,
      melanoma, and glioma. Interestingly, derivatives of FK506 that have the same
      FKBP12-binding properties as FK506 but lack functional immunosuppressant
      activity, exert the same apoptotic effect as FK506 in chronic lymphocytic
      leukemia.These findings suggest that a direct FKBP inhibition represents a
      further mechanism of immunosuppressants.' anticancer activity. In this review, we
      focus on the role of FKBP members in apoptosis control and summarize the data on
      the antitumor effect of selective targeting of FKBP.

PMID- 21182474
TI  - How to generate reliable and predictive CoMFA models.
AB  - Comparative Molecular Field Analysis (CoMFA) is a mainstream and down-to-earth 3D
      QSAR technique in the coverage of drug discovery and development. Even though
      CoMFA is remarkable for high predictive capacity, the intrinsic data-dependent
      characteristic still makes this methodology certainly be handicapped by noise.
      It's well known that the default settings in CoMFA can bring about predictive
      QSAR models, in the meanwhile optimized parameters was proven to provide more
      predictive results. Accordingly, so far numerous endeavors have been accomplished
      to ameliorate the CoMFA model's robustness and predictive accuracy by considering
      various factors, including molecular conformation and alignment, field
      descriptors and grid spacing. Herein, we would like to make a comprehensive
      survey of the conceivable descriptors and their contribution to the CoMFA model's
      predictive ability.

PMID- 21182475
TI  - Emerging targets for the treatment of dyslipidemia.
AB  - Dyslipidemia is one of the main risk factors leading to atherosclerotic
      cardiovascular disease (CVD). According to recent treatment guidelines, subjects
      at substantial risk of CVD should meet more aggressive targets for low-density
      lipoprotein(LDL)-cholesterol levels. Treatment with statins fails to protect a
      significant percentage of patients from cardiovascular events despite efficient
      cholesterol-lowering. Moreover, clinical and epidemiologic data highlight the
      need of therapies to reduce the residual cardiovascular risk associated with low
      high-density lipoprotein(HDL)-cholesterol and elevated triglyceride levels. There
      are several novel agents undergoing preclinical or clinical development for the
      treatment of dyslipidemia. Squalene synthase inhibitors, antisense
      oligonucleotides targeting the production of apolipoprotein(apo)B-100, inhibitors
      of proprotein convertase subtilisin/kexin type 9, microsomal triglyceride
      transfer protein inhibitors, peroxisome proliferator-activated receptor agonists,
      and thyroid hormone receptor agonists are some of the alternative approaches for
      lipid-lowering. Moreover, HDL-targeted therapies such as the cholesteryl ester
      transfer protein inhibitors, HDLderived proteins, and mimetic peptides/lipids can
      increase HDL-cholesterol levels or improve the antiatherosclerotic properties of
      HDL. In conclusion, the emergence of agents that act in monotherapy or in
      combination with available lipid-modifying drugs may allow more effective
      management of dyslipidemia and, consequently, reduce the burden of CVD.

PMID- 21182476
TI  - Novel aspects of neuronal differentiation in vitro and monitoring with advanced
      biosensor tools.
AB  - Neuronal differentiation is a very complex and sophisticated cellular process
      that encompasses the development of mature neurons and their specialization. In
      this review we will focus on the novel and less well-known aspects of neuronal
      differentiation. Cell lines, to which some pro-differentiation drugs are added,
      have been widely used because of their convenience in terms of cost-efficiency,
      ease of use and reproducibility. After a brief overview of these systems, this
      review focuses on the new pharmacological aspects of differentiation related to
      mitochondrial changes and cellular redox homeostasis. A number of different
      parameters are commonly evaluated to assess neuronal differentiation. These
      include neurite length, differential gene expression, mitochondrial mass, free
      radical levels, enzyme induction and others. However, the classical techniques
      used to detect neuronal differentiation (such as immunochemistry, flow cytometry
      and gene expression analysis) are time-consuming or dependent on the subjective
      view of the researcher. On the other hand, emerging novel, miniaturized biosensor
      technologies have the potential to revolutionize the study of neuronal
      differentiation, by detecting neuron-derived electrical signals and
      differentiation markers, such as shape or attachment in a non-invasive and high
      throughput fashion. These state-of-the-art technologies are being extensively
      reviewed. Emphasis is given to progress, made in the field of integrated systems
      (including impedance sensing, microfluidics and associated nanotechnologies),
      neuronal differentiation in 3-D cultures and the identification of novel agents
      controlling neuronal cell fate.

PMID- 21182477
TI  - Comparison of status epilepticus models induced by pilocarpine and nerve agents -
      a systematic review of the underlying aetiology and adopted therapeutic
      approaches.
AB  - Among potential radiological, nuclear, biological and chemical weapons,
      cholinergic nerve agents from chemical weapons remain a realistic terrorist
      threat due to its combination of high lethality, demonstrated use and relative
      abundance of un-destroyed stockpiles in various militaries around the world.
      While current fielded antidotes are able to mitigate acute poisoning, effective
      neuroprotection in the field remains a challenge amongst subjects with
      established status epilepticus following nerve agent intoxication. Due to
      ethical, safety and surety issues, extensive preclinical and clinical research on
      cholinergic nerve agents is not possible. This may have been a contributory
      factor for the slow progress in uncovering new neuroprotectants for nerve agent
      casualties with established status epilepticus. To overcome this challenge,
      comparative research with surrogate chemicals that produce similar
      hypercholinergic toxicity but with less security concerns would be a useful
      approach forward. In this paper, we will systemically compare the mechanism of
      seizure generation, propagation and the subsequent clinical, hematologic, and
      metabolic, biochemical, neuroinflammatory changes and current therapeutic
      approaches reported in pilocarpine, soman, and sarin models of seizures. This
      review will be an important first step in closing this knowledge gap among
      different closely related models of seizures and neurotoxicity. Hopefully, it
      will spur further efforts in using surrogate cholinergic models by the wider
      scientific community to expedite the development of a new generation of antidotes
      that are better able to protect against delayed neurological effects inflicted by
      nerve agents.

PMID- 21182478
TI  - Pleiotropic effects of cardioactive glycosides.
AB  - Cardioactive glycosides, like digoxin, ouabain and related compounds, are drugs
      that inhibit Na(+)/K(+)-ATPase and have a strong inotropic effect on heart: they
      cause the Na(+)/Ca(2+) exchanger to extrude Na+ in exchange with Ca(2+) and
      therefore increase the [Ca(2+)](i) concentration. For this reason, some of these
      drugs are currently used in the treatment of congestive heart failure and cardiac
      arrhythmias. Recently it has been discovered that cardiac glycosides exert
      pleiotropic effects on many aspects of cell metabolism. Na(+)/K(+)-ATPase is not
      the exclusive target, as they affect the cell response to hypoxia, modulate
      several signaling pathways involved in cell death and proliferation, regulate the
      transcription of different genes and modify the pharmacokinetics of other drugs,
      by altering the expression and activity of drug-metabolizing enzymes. Some of
      these effects are related to the steroid structure of glycosides, a property
      which also makes them fine modulators of the synthesis of cholesterol and steroid
      hormones. Moreover, new endogenously synthesized glycosides have been discovered
      in the last years: these molecules are involved in the balance of salt and in the
      control of blood pressure. This review will focus on the recent studies which
      have demonstrated that exogenous and endogenous glycosides, besides playing a
      role as inotropic agents, are also important in the pathogenesis and therapy of
      different human diseases, such as stroke, diabetes, neurological diseases and
      cancer.

PMID- 21182473
TI  - Emerging role of antioxidants in the protection of uveitis complications.
AB  - Current understanding of the role of oxidative stress in ocular inflammatory
      diseases indicates that antioxidant therapy may be important to optimize the
      treatment. Recently investigated antioxidant therapies for ocular inflammatory
      diseases include various vitamins, plant products and reactive oxygen species
      scavengers. Oxidative stress plays a causative role in both non-infectious and
      infectious uveitis complications, and novel strategies to diminish tissue damage
      and dysfunction with antioxidant therapy may ameliorate visual complications.
      Preclinical studies with experimental animals and cultured cells demonstrate
      significant anti-inflammatory effects of a number of promising antioxidant
      agents. Many of these antioxidants are under clinical trial for various
      inflammatory diseases other than uveitis such as cardiovascular, rheumatoid
      arthritis and cancer. Well planned interventional clinical studies in the field
      of ocular inflammation will be necessary to sufficiently investigate the
      potential medical benefits of antioxidant therapies for uveitis. This review
      summarizes the recent investigations of novel antioxidant agents for ocular
      inflammation, with selected studies focused on uveitis.

PMID- 21182479
TI  - Road towards new antimalarials - overview of the strategies and their chemical
      progress.
AB  - Malaria is a major health and economic threat to about 40% of the world's
      population. The absence of effective vaccines and widespread resistance to many
      of the current antimalarials make this disease an urgent target for the
      scientific community. As a developing world disease, most of the efforts towards
      new drugs have been from academic and government supported projects. This has
      recently changed with the emergence of new funding mechanisms and public-private
      partnerships (PPP). The purpose of this review is to highlight the different
      approaches used to discover new antimalarial agents, including target-based
      approaches, derivatization of known antimalarial pharmacophores, drug
      repositioning from non-malaria indication and cell-based screening. Specific
      examples are provided to illustrate the pros and cons in the context of how to
      best address the ever-increasing drug resistance and how to cost-effectively
      identify new antimalarials. More attention is given to relatively mature programs
      that have gone through extensive SAR study, pharmacology and/or toxicity studies
      in the last ten years.

PMID- 21182480
TI  - New targets for antibacterial design: Kdo biosynthesis and LPS machinery
      transport to the cell surface.
AB  - Lipopolysaccharide (LPS), which constitutes the lipid portion of the outer
      leaflet of Gram-negative bacteria, is essential for growth. It is also
      responsible for the variety of biological effects associated with Gram-negative
      sepsis. Recent advances have elucidated the exact chemical structure of this
      highly complex macromolecule and much of the enzymology involved in its
      biosynthesis. Enzymes involved in LPS biogenesis are optimal targets for the
      development of novel therapeutics since they are sufficiently conserved among
      diverse, clinically-relevant bacteria and no analogue counterpart is present in
      humans. During the last thirty years a number of inhibitors of LPS biosynthesis
      have been developed: some of these compounds have antibacterial properties, while
      others show excellent in vitro activity and are undergoing further investigation.
      The main focus of this review will be the biology of LPS in bacteria summarizing
      the knowledge about structure and enzymatic catalysis, as well as chemical
      efforts towards the synthesis of inhibitors of the key enzymes involved in the
      biosynthesis of Kdo, toward the minimal conserve structure Kdo(2)-LipA. In
      addition, very recent advances in deciphering the molecular mechanisms of LPS
      transport to the cell surface, as a new target to develop novel antibacterials,
      will be reported. Future directions and perspectives will also be outlined.

PMID- 21182481
TI  - Natural products as anti-invasive and anti-metastatic agents.
AB  - Invasion and metastasis, the hallmark of malignant tumor, is the main reason for
      the clinical death of most cancer patients. Tumor invasion and metastasis are
      complex, multi-step biochemical processes, which involve cell detachment,
      invasion, migration, intravasation and circulation, implantation, angiogenesis
      and proliferation. Therefore, how to prevent tumor metastasis has been the
      biggest challenge in cancer chemotherapy. In recent years, many natural products
      have been found to have anti-invasive and anti-metastatic activities. In this
      paper, these natural compounds are classified as polyphenols, terpenoids,
      alkaloids, steroids and saponins, saccharides, macrolides, amides and others,
      their anti-invasive and anti-metastatic activities as well as their biological
      targets are reviewed.

PMID- 21182482
TI  - Anticancer active illudins: recent developments of a potent alkylating compound
      class.
AB  - An overview of anticancer active spirocyclopropanes of the illudin class is
      provided. After a short introduction on the history and general chemistry of
      illudins M and S, new discoveries concerning their mode of action and metabolism
      are reported as well as new synthetic endeavors towards derivatives with improved
      selectivity for and efficacy against cancer cells. In addition, common and
      recently tapped biological sources and isolation procedures for known and new
      illudins are discussed. Pertinent literature is covered up to 2010.

PMID- 21182483
TI  - Chemistry and pharmacology of neglected helminthic diseases.
AB  - Neglected helminthic diseases cause many social, economic and health care
      challenges in developing countries. The high number of patients suffering from
      these parasitic infections and the lack of sufficient treatment options represent
      severe problems. Research on new drugs and therapies to meet this urgent
      requirement has to be intensified. This review focuses on infections caused by
      four helminthic parasites, which have been declared as neglected diseases by the
      World Health Organization: namely drancunculiasis, lymphatic filariasis,
      onchoceriasis, and schistosomiasis. They show a considerable overlap in their
      world-wide prevalence and treatment strategies. Nevertheless, treatment is not
      without complications. The most efficient lymphatic filariasis drug,
      diethylcarbamazine, causes severe adverse effects in onchocerciasis patients and
      completely fails in the treatment of drancunculiasis. In this review, we discuss
      these incongruities at the molecular and cellular level. Furthermore, established
      or investigational drug combination regimens are highlighted. In the past years,
      progress has been made in the area of schistosomiasis and onchocerciasis. The
      molecular biology of underlying mechanisms, signalling pathways and related
      targets affected by drug therapy are discussed in detail. Finally, successful
      treatment strategies and remaining future challenges are summarized.

PMID- 21182484
TI  - New lead structures in antifungal drug discovery.
AB  - During the past two decades, the incidence of invasive fungal infections has been
      increasing dramatically. Clinical available antifungal agents have several
      drawbacks such as limited potency and spectrum, drug related toxicity, non
      optimal pharmacokinetics, and severe resistance. There is an emergent need to
      develop new antifungal drugs with novel chemical structures and novel mechanism
      of action. This review will focus on the most significant achievements in the
      discovery of antifungal lead structures within last few years. In particular, we
      pay more attention on the structure-activity relationship of antifungal leads and
      provide perspectives for future antifungal drug discovery.

PMID- 21182485
TI  - Toward a biochemical diagnosis of NASH: insights from pathophysiology for
      distinguishing simple steatosis from steatohepatitis.
AB  - With the continuing epidemics of obesity and diabetes, nonalcoholic fatty liver
      disease (NAFLD) has received increased attention. Great efforts are being
      undertaken to improve the noninvasive diagnosis of NAFLD, with the ultimate goal
      of optimizing treatment options and clinical outcomes. Research suggests that
      blood-borne biochemical markers can be used to distinguish simple steatosis from
      nonalcoholic steatohepatitis (NASH), thus reducing the need of liver biopsy.
      Future developments in the field of diagnostic biochemistry within the spectrum
      of NAFLD can make this approach ideal for screening and monitoring purposes. In
      this review, we provide an overview of the different blood-borne markers which
      have been recently proposed for differentiating simple steatosis from NASH. We
      will also consider the practical and statistical issues that seem to be limiting
      the effective integration of biomarkers into clinical development.

PMID- 21182486
TI  - Pharmacological interventions on asymmetric dimethylarginine, a clinical marker
      of vascular disease.
AB  - The aim of this paper is to review the latest data on the pharmacological
      modulation of asymmetric dimethylarginine in human disease. When the terminal
      nitrogens of the guanidine portion of an arginine become methylated through the
      action of N-methyl transferases, two chemically close, but physiologically
      different amino acids are synthesized: symmetric and asymmetric dimethylarginine.
      The vascular origin of asymmetric dimethylarginine and its inhibitory activity on
      endothelial nitric oxide synthase give it an important role in certain diseases
      in which microcirculation is compromised: hypertension, atherosclerosis,
      inflammatory bowel disease, and diabetes. This review discusses the role that
      asymmetric dimethylarginine plays in the development of vascular disease, and,
      wherever possible, evaluates its use in clinical diagnosis. The fact that a
      number of chemically unrelated drugs, such as angiotensin II antagonists,
      selective beta- 1 adrenergic antagonists, plant phenolics, statins, and farnesoid
      X receptor agonists have all been found to reduce dimethylarginine levels in
      plasma or tissue allows for an integrated study. Although it is difficult to
      determine exactly why these various agents all have the same effect on arginine
      metabolism, an explanation of their mechanisms of action is needed. We have thus
      analyzed the mechanisms involved and reviewed potential trends in the therapeutic
      use of these drugs.

PMID- 21182487
TI  - Clinical drugs undergoing polymorphic metabolism by human cytochrome P450 2C9 and
      the implication in drug development.
AB  - CYP2C9 metabolizes more than 100 clinically used drugs including phenytoin, S
      warfarin, tolbutamide, glipizide, diclofenac, and losartan with varying
      contributions. CYP2C9 is considered one of the most important CYPs, with
      substrate specificity typical of many new chemical entities (i.e. lipophilic
      bases). A large interindividual variation has been identified for the CYP2C9
      activity and for the clinical response to the therapeutics metabolised by the
      enzyme. So far, at least 33 variants of CYP2C9 (*2 through to *34) have been
      identified. CYP2C9 is one of the clinically significant drug metabolising enzymes
      that demonstrates genetic variants with significant phenotype and clinical
      outcomes. This review updates our current knowledge on the polymorphic metabolism
      of drugs by CYP2C9 and discusses its implications in drug development. The
      authors have searched through computer-based literatures by full text search in
      Medline (via Pubmed), ScienceDirect, Genetics Abstracts (CSA), SCOPUS, Chemical
      Abstracts, Current Contents Connect (ISI), Cochrance Library, CINAHL (EBSCO),
      CrossRef Search and Embase (all from inception to October 31 2010). A
      comprehensive literature search has identified 32 drugs that are subject to
      CYP2C9-mediated polymorphic metabolism. Drugs that are subject to polymorphic
      metabolism with clinical significance include nine nonsteroidal anti-inflammatory
      agents, six sulfonylurea antidiabetic drugs and, most critically, three oral
      coumarin anticoagulants. Polymorphisms in CYP2C9 have the potential to affect the
      clearance and clinical response of CYP2C9 substrate drugs with low therapeutic
      indices such as warfarin, phenytoin, and certain antidiabetic drugs. Warfarin has
      served as a model drug of how pharmacogenetics can be employed to achieve maximum
      efficacy and minimum toxicity. Minimizing interindividual variability in drug
      exposure due to CYP2C9 polymorphisms is an important goal in drug development and
      discovery.

PMID- 21182488
TI  - Novel and emerging drugs for acute myeloid leukemia: pharmacology and therapeutic
      activity.
AB  - For the last twenty years, significant progress in Molecular and Cellular Biology
      has resulted in a better characterization and understanding of the biology and
      prognosis of acute myeloid leukemia (AML). These achievements have provided new
      opportunities for the development of innovative, more effective therapies. Novel
      agents potentially useful in the treatment of patients with AML include new
      formulations of established drugs, newer nucleoside analogs, molecular target
      drugs, monoclonal antibodies and other agents. Three newer nucleoside analogs,
      clofarabine, troxacitabine and sapacitabine have been recently investigated in
      patients with AML. Two methylation inhibitors, 5-azacyticline and decitabine are
      pyrimidine nucleoside analogs of cytidine which can be incorporated into RNA
      and/or DNA. Lower doses of these agents are active in AML and have been
      extensively investigated, especially in secondary AML and AML in elderly
      patients. Tipifarnib and lonafarnib are orally available farnesyltransferase
      inhibitors with in vitro and in vivo activity against AML. In recent years, FLT3
      inhibitors, lestaurinib, tandutinib and PKC 412 have been developed and tested in
      AML. The preclinical observations and clinical studies indicate that FLT3
      inhibitors are promising agents in the treatment of FLT3 mutated AML patients,
      especially when used in combinations with chemotherapy. Several newer MDR
      inhibitors, including valspodar (PSC-833) and zosuquidar trihydrochloride have
      been also tested for the treatment of relapsed AML. This article reviews the
      various classes of AML targets and drugs that are under early phase clinical
      evaluation, especially those that are likely to enter clinical practice in the
      near future.

PMID- 21182489
TI  - Proteinuria in diabetes: an endocrine disease?

PMID- 21182490
TI  - Cannabidiol improves brain and liver function in a fulminant hepatic failure
      induced model of hepatic encephalopathy in mice.
AB  - BACKGROUND AND PURPOSE: Hepatic encephalopathy is a neuropsychiatric disorder of
      complex pathogenesis caused by acute or chronic liver failure. We investigated
      the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa
      with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor
      5-HT(1A) , on brain and liver functions in a model of hepatic encephalopathy
      associated with fulminant hepatic failure induced in mice by thioacetamide.
      EXPERIMENTAL APPROACH: Female Sabra mice were injected with either saline or
      thioacetamide and were treated with either vehicle or cannabidiol. Neurological
      and motor functions were evaluated 2 and 3 days, respectively, after induction of
      hepatic failure, after which brains and livers were removed for histopathological
      analysis and blood was drawn for analysis of plasma liver enzymes. In a separate
      group of animals, cognitive function was tested after 8 days and brain 5-HT
      levels were measured 12 days after induction of hepatic failure. KEY RESULTS:
      Neurological and cognitive functions were severely impaired in thioacetamide
      treated mice and were restored by cannabidiol. Similarly, decreased motor
      activity in thioacetamide-treated mice was partially restored by cannabidiol.
      Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as
      enhanced 5-HT levels in thioacetamide-treated mice were normalized following
      cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide
      treated mice was moderated after cannabidiol treatment. CONCLUSIONS AND
      IMPLICATIONS: Cannabidiol restores liver function, normalizes 5-HT levels and
      improves brain pathology in accordance with normalization of brain function.
      Therefore, the effects of cannabidiol may result from a combination of its
      actions in the liver and brain.

PMID- 21182492
TI  - Modulation of the late sodium current by ATX-II and ranolazine affects the
      reverse use-dependence and proarrhythmic liability of IKr blockade.
AB  - BACKGROUND AND PURPOSE: Drug-induced torsades de pointes (TdP) often occurs
      during bradycardia due to reverse use-dependence. We tested the hypothesis that
      inhibition or enhancement of late sodium current (I(Na,L) ) could modulate the
      drug-induced reverse use-dependence in QT and T(p-e) (an index of dispersion of
      repolarization), and therefore the liability for TdP. EXPERIMENTAL APPROACH:
      Arterially perfused rabbit left ventricular wedge preparations were used. Action
      potentials from the endocardium were recorded simultaneously with a transmural
      ECG. The effects of Anemonia sulcata toxin (ATX-II) (an I(Na,L) enhancer), d,l
      sotalol, clarithromycin and ranolazine (an I(Na,L) blocker) on rate-dependent
      changes in QT, T(p-e) and proarrhythmic events were tested, either alone or in
      combination. Rate-dependent QT and T(p-e) slopes and TdP score (a combined index
      of TdP liability) were calculated at control and during drug infusion. KEY
      RESULTS: ATX-II (30 nM) and sotalol (300 uM) caused a marked increase in QT and
      T(p-e) intervals, steeper QT-basic cycle length (BCL) and T(p-e) -BCL slopes
      (i.e. reverse use-dependence), and TdP. Addition of ranolazine (15 uM) to ATX-II
      or sotalol significantly attenuated QT-BCL, T(p-e) -BCL slopes and the increased
      TdP scores. In contrast, clarithromycin (100 uM) moderately prolonged QT and T(p
      e) without causing R-on-T extrasystole or TdP, but addition of ATX-II (1 nM) to
      clarithromycin markedly amplified the QT-BCL and T(p-e) -BCL slopes and further
      increased TdP score. CONCLUSION AND IMPLICATIONS: Modulation of I(Na,L) altered
      drug-induced reverse use-dependence related to QT as well as T(p-e) , indicating
      that inhibition of I(Na,L) can markedly reduce the TdP liability of agents that
      prolong QT intervals.

PMID- 21182491
TI  - Effect of transdermal opioids in experimentally induced superficial, deep and
      hyperalgesic pain.
AB  - BACKGROUND AND PURPOSE: Chronic pain and hyperalgesia can be difficult to treat
      with classical opioids acting predominately at the u-opioid receptor.
      Buprenorphine and its active metabolite are believed to act through u-, kappa-
      and delta-receptors and may therefore possess different analgesic and anti
      hyperalgesic effects compared with pure u-receptor agonists, for example,
      fentanyl. Here, we have compared the analgesic and anti-hyperalgesic effects of
      buprenorphine and fentanyl. EXPERIMENTAL APPROACH: Twenty-two healthy volunteers
      were randomized to treatment with transdermal buprenorphine (20 ug.h(-1), 144 h),
      fentanyl (25 ug.h(-1), 72 h) or placebo patches in a double-blind, cross-over
      experimental pain study. The experimental pain tests (phasic pain, sensitization)
      involved pressure at the tibial bone, cutaneous electrical and thermal
      stimulation, intramuscular nerve growth factor, UVB light burn injury model and
      intradermal capsaicin-induced hyperalgesia. Pain testing was carried out at
      baseline, 24, 48, 72 and 144 h after application of the drugs. KEY RESULTS:
      Compared with placebo, buprenorphine, but not fentanyl, significantly attenuated
      pressure at the tibial bone as well as pressure pain in the primary hyperalgesic
      area induced by UVB light The two drugs were equipotent and better than placebo
      against cutaneous thermal pain stimulation), but failed to show significant
      analgesic effect to cutaneous electrical stimulation, nerve growth factor-induced
      muscle soreness and to capsaicin-induced hyperalgesia. CONCLUSIONS AND
      IMPLICATIONS: Buprenorphine, but not fentanyl, showed analgesic effects against
      experimentally induced, bone-associated pain and primary hyperalgesia compared
      with placebo. These tissue- and modality-differentiated properties may reflect
      the variable effects of opioid drugs observed in individual patients.

PMID- 21182493
TI  - Elucidation of flow-mediated tumour cell-induced platelet aggregation using an
      ultrasound standing wave trap.
AB  - BACKGROUND AND PURPOSE: Tumour cells activate and aggregate platelets [tumour
      cell-induced platelet aggregation (TCIPA)] and this process plays an important
      role in the successful metastasis of cancer cells. To date, most studies on TCIPA
      have been conducted under no-flow conditions. In this study, we have investigated
      TCIPA in real time under flow conditions, using an ultrasound standing wave trap
      that allows formation and levitation of cancer cell clusters in suspension, thus
      mimicking the conditions generated by flowing blood. EXPERIMENTAL APPROACH: Using
      59M adenocarcinoma and HT1080 fibrosarcoma cells and human platelets, cancer cell
      cluster-platelet aggregates were imaged in real time using epi-fluorescence
      microscopy (F-actin) and investigated in detail using confocal microscopy (matrix
      metalloproteinase-2-GPIIb/IIIa co-localization) and scanning electron and helium
      ion microscopy (<1 nm resolution). The release of gelatinases from aggregates was
      studied using zymography. KEY RESULTS: We found that platelet activation and
      aggregation takes place on the surface of cancer cells (TCIPA), leading to time
      dependent disruption of cancer cell clusters. Pharmacological modulation of TCIPA
      revealed that EDTA, prostacyclin, o-phenanthroline and apyrase significantly down
      regulated TCIPA and, in turn, delayed cell cluster disruption, However, EGTA and
      aspirin were ineffective. Pharmacological inhibition of TCIPA correlated with the
      down-regulation of platelet activation as shown by flow-cytometry assay of
      platelet P-selectin. CONCLUSION AND IMPLICATIONS: Our results show for the first
      time, that during TCIPA, platelet activation disrupts cancer cell clusters and
      this can contribute to metastasis. Thus, selective targeting of platelet
      aggregate-cancer cell clusters may be an important strategy to control
      metastasis.

PMID- 21182495
TI  - A practical, algorithmic approach to diagnosing hair shaft disorders.
AB  - The hair shaft is a unique structure composed of an inner cortex and a protective
      outer cuticle. Any defects in this normal structure due to genetics or the
      environment can lead to variations in physical properties. Thus one should
      suspect a hair shaft disorder if a patient presents with an abnormality or change
      in hair texture, appearance, manageability or ability to grow hair long. A key
      feature of the clinical evaluation is to determine whether there is hair breakage
      (increased fragility) by looking for broken hairs and performing a tug test. Once
      this determination is made, an algorithmic approach can be used to narrow the
      differential diagnosis: hair shaft disorders with and without fragility. A hair
      mount along with other directed questions and examination will almost always
      allow the clinician to make an in-office diagnosis. Common case scenarios,
      photographs, and practical tips are provided to illustrate the use of this
      algorithmic approach in the diagnosis of hair shaft disorders. We have also
      included a summary of the molecular defects where known, which can be helpful in
      providing a correlation with clinical findings, in counseling patients, and
      potentially offering treatment options.

PMID- 21182494
TI  - Developing the next generation of monoclonal antibodies for the treatment of
      rheumatoid arthritis.
AB  - Rheumatoid arthritis is one of the commonest autoimmune diseases affecting 0.8%
      of the population. Over the last decade the treatment of this chronic disease has
      been revolutionized by the use of monoclonal antibodies and fusion proteins,
      targeting molecules like tumour necrosis factor alpha. Nevertheless,
      approximately one-third of subjects fail to respond to these therapies and
      therefore significant unmet medical need remains. Following a decade of use,
      clinical, government and regulatory agency expectations have changed for new
      antibodies therapies entering this highly competitive area. In this review, we
      discuss the current advances being made in antibody engineering and how they are
      being considered and used in the development of the next generation of antibodies
      to meet future expectations of healthcare providers, physicians and patients.
      Moreover, we discuss how pattern recognition receptors may provide new antibody
      tractable targets that may break the cycle of autoimmunity in rheumatoid
      arthritis.

PMID- 21182496
TI  - Tuberous sclerosis complex: tumors and tumorigenesis.
AB  - Tuberous sclerosis complex (TSC) is an inherited disorder characterized by
      hamartomas in different body organs, mainly in the brain, skin, kidney, liver,
      lung, and heart. The clinical manifestations of TSC are the result of a mutation
      of one of two tumor suppressor genes, TSC1 and TSC2. Cutaneous findings in TSC
      should be regarded as cutaneous signs of a pivotal systemic disease. The authors
      elucidate the variety of neoplasms seen in TSC patients, along with their
      clinical significance, and suggest suitable evaluation and management strategies.

PMID- 21182497
TI  - The significance of anticardiolipin antibody and immunologic abnormality in
      livedoid vasculitis.
AB  - OBJECTIVE: To evaluate the significance of anticardiolipin and immunologic
      abnormality in the livedoid vasculitis (LV). METHODS: 30 patients with biopsy
      proven LV and 30 normal controls involved in the study. Indirect
      immunofluorescence, immunoblot, and ELISA were used for detecting antinuclear
      antibody (ANA), circulating immune complex, immune globulin,
      anticardiophospholipin antibody (ACA), and anti-beta(2) GP1. RESULTS: ANA was
      positive in four patients with LV, and among them, two patients were diagnosed as
      Systemic Lupus Erythematosus (SLE) later. Addition to the two SLE patients, the
      level of ENA and immunoglobulin were normal in the rest of patients.
      Anticardiolipin antibodies were present in 13 (43.33%), and beta(2) GP1 was
      present in nine (30%) of 30 patients. There were significant differences between
      LV and controls. CONCLUSIONS: ACA is one of important pathogenesis of LV.
      Numerous heterogeneous coagulation abnormalities and thrombogenesis may involve
      the LV.

PMID- 21182498
TI  - Immunohistochemical expression of cyclooxygenage-2 in melanocytic skin lesions.
AB  - BACKGROUND: Several reports have shown expression of cyclooxygenase-2 (COX-2) in
      malignant skin tumors. COX-2 has also recently been reported as a marker of
      malignant melanoma (MM). OBJECTIVE: Our aim was to investigate whether there is a
      difference in the immunohistochemical expression of COX-2 between malignant and
      benign melanocytic lesions of the skin. METHODS: We selected 40 archival cases of
      MM including 10 cases of superficial spreading melanoma, 10 of lentigo maligna
      melanoma, 10 of nodular melanoma, and 10 of acral lentiginous melanoma. For
      comparison, we also selected 35 benign melanocytic lesions, which included 15
      nonatypical nevi and 10 atypical nevi. The remaining 10 cases were Spitz nevi.
      COX-2 immunohistochemical staining was performed, and intensities were assessed
      quantitatively. RESULTS: The MM group and the benign melanocytic nevi group
      showed a highly statistically significant difference in the intensity of COX-2
      expression (P < 0.0001). Staining intensity in the dermal component of MM cases
      also showed a tendency to increase with increasing tumor depth. By contrast, the
      intensity of the dermal component in the melanocytic nevi group decreased with
      increasing depth as the nevus cells matured from type A to type C cells. No
      statistical difference was noted between the MM and Spitz nevi cases (P = 0.20).
      CONCLUSIONS: Malignant melanoma shows stronger immunohistochemical expression of
      COX-2 than benign melanocytic nevi. Although COX-2 cannot be used alone to
      differentiate MM from melanocytic nevi, it may serve as an aid in the
      differential diagnosis of melanocytic skin lesions.

PMID- 21182499
TI  - Assessment of osteoporosis in psoriasis with and without arthritis: correlation
      with disease severity.
AB  - BACKGROUND: The most frequent extracutaneous association with psoriasis is
      arthritis. Because proinflammatory cytokines are increased in psoriasis, patients
      with this disease may be more prone to osteoporosis than the healthy individuals.
      METHODS: We evaluated 50 patients with psoriasis, with or without psoriatic
      arthritis (PsA), for the presence and degree of osteoporosis by performing dual
      energy x-ray absorptiometry (DEXA) and obtaining serum osteoprotegrin (OPG)
      levels. In addition, we correlated these results with the extent of skin and
      joint disease. Psoriasis area and severity index (PASI) was determined in all 50
      patients with psoriasis, and total joint score (TJS) was recorded in the 16
      patients who also had PsA. Results of DEXA and serum OPG were also obtained for
      20 healthy individuals who served as controls. RESULTS: Osteoprotegrin level was
      significantly increased in psoriasis patients (with or without PsA) vs. controls.
      However, DEXA revealed that PsA patients had a higher degree of osteoporosis in
      the femur neck and wrist. In PsA patients, TJS correlated positively with both
      disease duration and PASI but correlated negatively with Z score of the femur.
      CONCLUSION: Psoriasis patients with or without arthritis may suffer from
      osteoporosis as evidenced by significantly increased serum OPG. Prolonged and
      extensive cutaneous disease is an important risk factor for the development and
      severity of PsA. Patients with a greater number of affected joints are at higher
      risk of osteoporosis.

PMID- 21182500
TI  - Prurigo pigmentosa: a clinicopathological study and analysis of associated
      factors.
AB  - BACKGROUND: Prurigo pigmentosa (PP), a rare inflammatory disease of the skin, is
      mostly reported in the ethnic Japanese population. Its pathogenesis remains
      unclear. The chronic and recurrent nature of PP implies a possible role of viral
      infection in the pathogenesis. The anti-inflammatory mechanism of doxycycline,
      which is well documented as a good treatment for PP, is related to the
      suppression of interleukin expression. METHODS: We identified and retrospectively
      analyzed 16 biopsy-proven and criteria-matched patients over a seven year period
      at a single medical center. DNA extracted from formalin-fixed, paraffin-embedded
      specimens was analyzed for herpes simplex virus-1 (HSV-1), HSV-2, and human
      herpes virus-6 (HHV-6) DNA by polymerase chain reaction. Immunohistochemistry was
      performed to determine the interleukin-6 (IL-6) and interleukin-8 (IL-8)
      expression in PP skin lesions. RESULTS: Clinicopathological findings in the
      ethnic Chinese population are similar to those reported in Japanese studies. All
      patients had a good response to doxycycline treatment, with a mean duration of
      use of 2.4 weeks. However, recurrence was noted in six patients. HSV-1, HSV-2,
      and HHV-6 DNA in PP skin lesions were negative. Immunohistochemistry showed IL-6
      (P = 0.035) to be more strongly expressed in PP skin lesions. There was no
      statistical significance of elevated IL-8 expression in PP (P = 0.123).
      CONCLUSIONS: Prurigo pigmentosa is not uncommon in the ethnic Chinese population.
      There was no evidence of herpes virus DNA in PP skin lesions. Increased
      expression of IL-6 in PP skin lesions may explain the effects of doxycycline in
      terms of its anti-inflammatory properties.

PMID- 21182501
TI  - Measuring performance in skin cancer practice: the SCARD initiative.
AB  - BACKGROUND: The Skin Cancer College of Australia and New Zealand (SCCANZ) has
      developed a unique project named SCARD - the Skin Cancer Audit and Research
      Database. Designed initially as a self-audit tool for primary care skin cancer
      practitioners, SCARD acts as a tracking tool to enhance practice safety, and it
      also creates practice performance reports. Pooling of de-identified data enables
      participating practitioners to confidentially compare their own practice to that
      of their peers. Additionally, this creates a large database with significant
      research potential, as SCARD records for every lesion de-identified practitioner
      and patient data, and extensive details of location, provisional and histological
      diagnosis, and the procedure(s) performed in its treatment. METHODS: Preliminary
      data collected in the database have been presented in this study. RESULTS: An
      initial pool of data from 177 practitioners contains 77,553 specimens from 41,006
      individual patients. CONCLUSIONS: The data presented are being analyzed for
      further studies, and additional data continues to be collected from this ongoing
      project. SCARD is a useful tool at practice level, and substantial uptake by
      Australian primary care skin cancer practitioners has provided a unique
      opportunity for research into skin cancer and its management. SCCANZ, a
      professional college of predominantly primary care medical practitioners, with a
      commitment to the management of skin cancer in Australia and New Zealand, has
      formed a partnership with the School of Medicine at the University of Queensland
      to ensure that these data are managed and analyzed appropriately.

PMID- 21182502
TI  - A novel homozygous splice site mutation in COL7A1 in a Chinese patient with
      severe recessive dystrophic epidermolysis bullosa and squamous cell carcinoma.
AB  - BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited
      blistering skin disorder caused by mutations in COL7A1 gene encoding type VII
      collagen, the major component of anchoring fibrils in the dermo-epidermal
      junction. The development of cutaneous squamous cell carcinoma (SCC) is one of
      the most serious complications of this disease. We report herein a Chinese
      patient with the severe generalized subtype of RDEB (RDEB-sev gen) complicated by
      SCC. METHODS: Skin biopsies were examined for histology, basement membrane
      ultrastructure, and type VII collagen expression. Genomic DNA was extracted from
      the peripheral blood samples and subjected to polymerase chain reaction
      amplification and direct automated DNA sequencing. RESULTS: Histopathological
      examination of the patient's skin revealed an undetectable expression of type VII
      collagen polypeptides in the basement membrane zone. Mutation analysis identified
      a novel splice site mutation in intron 64 (IVS64+5g->a) of COL7A1 gene, which
      resulted in an in-frame deletion of exon 64 in both alleles. CONCLUSIONS: This
      report contributes to the expanding database of COL7A1 mutations and emphasizes
      the need to elucidate the underlying genetic mechanisms associated with the
      increased incidence of SCC in RDEB patients.

PMID- 21182503
TI  - Causes of death among active leprosy patients in China.
AB  - We analyzed the causes of death among active leprosy patients in China, to better
      understand the disease and improve the quality of services, by performing a
      retrospective study involving 24 provinces of China. Information about patients
      with active leprosy who were not clinically cured and died between January 1,
      2000, and December 31, 2005, was collected by professionals at county levels. A
      total of 524 deaths were analyzed. The leading cause of death was suicide. There
      were 86 patients (16%) who died at a mean of 21 +/- 19 months after starting
      multi-drug therapy (MDT). The second and third leading causes of death were
      cardiovascular disease and organ failure associated with advanced age,
      respectively. Two hundred and twenty-one patients (42%) died within one year of
      beginning MDT. The second month of MDT was the riskiest for newly treated
      patients; approximately 20% of patients succumbed to liver failure, 33% to
      dapsone (diaminodiphenylsulfone/DDS) allergy, and 27% to renal insufficiency
      during this period. Among 143 deaths related to leprosy, 37 (26%) occurred within
      three months of starting MDT. We recommend that newly diagnosed patients should
      be provided with no more than two months of MDT blister packs.

PMID- 21182504
TI  - Purpuric macules with vesiculobullous lesions: a novel manifestation of
      Chikungunya.
AB  - BACKGROUND: Chikungunya (CHIK) is an emerging viral disease with a myriad of
      cutaneous manifestations. AIMS: The aim of our study was to document the
      morphology and evolution of skin lesions in cases presenting with fever, purpuric
      macules and vesiculobullous lesions, to confirm its causative relationship with
      CHIK, and to investigate further in order to delineate possible mechanisms of
      bulla formation in these cases. MATERIALS AND METHODS: A prospective, descriptive
      hospital-based study was carried out at a tertiary health care centre in Kerala.
      A total of 10 patients were enrolled in the study and investigated. RESULTS: All
      cases had morbilliform eruption prior to onset of purpuric macules. Eight cases
      developed vesiculobullous lesions that arose either de novo or over a part or
      whole of the purpuric macules. Skin lesions resolved within an average of 7.6
      days leaving post-inflammatory hypopigmentation. IgM CHIK enzyme-linked
      immunosorbent assay (ELISA) was positive in all 10 patients. Tzanck smear from
      the bullae showed lymphocytes in most cases along with acantholytic cells,
      necrotic keratinocytes or occasional neutrophils. Skin biopsy showed
      intraepidermal or subepidermal bullae. Immunohistochemistry revealed
      predominantly CD8 positive T lymphocytes in the infiltrate. The prognosis was
      good with supportive management alone. DISCUSSION: The clinical features in our
      cases are comparable to the 3 previous reports of vesiculobullous lesions in CHIK
      affected infants. Based on the current evidence, we hypothesize that at least 2
      mechanisms are at play for these skin lesions; CHIK virus induced keratinocyte
      necrosis followed by a cytotoxic immune response, and possible modulation of rash
      by drugs. CONCLUSION: With severe epidemics of CHIK spreading from Asia and
      Africa to the Western hemisphere, we must consider bullous CHIK as a differential
      diagnosis in cases with fever and purpuric and vesiculobullous lesions.

PMID- 21182505
TI  - Juvenile temporal arteritis with perifollicular lymphoid proliferation resembling
      Kimura disease. Report of a case.

PMID- 21182506
TI  - A case of juvenile dermatomyositis with severe calcinosis and successful
      treatment with prednisone and diltiazem.

PMID- 21182508
TI  - Cutaneous metastasis to face and neck as a sole manifestation of an unsuspected
      renal cell carcinoma.

PMID- 21182507
TI  - Nicolau syndrome after lidocaine injection and cold application: a rare
      complication of breast core needle biopsy.

PMID- 21182509
TI  - Full-spectrum light phototherapy for atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic skin disease resulting in a
      profound deterioration in quality of life. The FSL(r) is a newly developed
      phototherapy device generating full-spectrum light (FSL) with a continuous
      wavelength (320-5000 nm). This study aimed to evaluate the efficacy and safety of
      FSL(r) phototherapy in AD. METHODS: We enrolled 38 patients with moderate to
      severe AD in this open, randomized, controlled, prospective study. In the FSL
      irradiated group (20 patients), irradiation was conducted twice per week for 4
      consecutive weeks. In the control group (18 patients), only emollient application
      was allowed. SCORing Atopic Dermatis (SCORAD) values were obtained at baseline,
      week 4 and 8. Patients were asked to give subjective assessments of improvement
      and laboratory tests including serum eosinophil counts, ECP levels, IgE levels
      and 22 cytokine levels were performed. RESULTS: In the FSL-irradiated group, the
      mean SCORAD value decreased significantly after 4 weeks of phototherapy and
      remained reduced for a further 4 weeks after the cessation of treatment. In the
      control group, the mean SCORAD value did not change significantly over the study
      period. Patients' subjective assessments indicated good to excellent responses in
      75% of the FSL-irradiated group, by contrast with 50% of the control group. The
      mean values for serum eosinophil counts, IL-4 and IL-5 levels decreased
      significantly after FLS phototherapy. No serious adverse effects were reported.
      CONCLUSIONS: In this study, we showed that FSL(r) phototherapy can be an
      effective and safe treatment option in AD.

PMID- 21182510
TI  - Epidermal changes associated with symptomatic resolution of dandruff: biomarkers
      of scalp health.
AB  - BACKGROUND: Dandruff is a common scalp condition characterized by flakes,
      pruritus and sometimes mild erythema. These symptoms reflect underlying
      histopathologic and biochemical events that must be reversed if treatment is to
      be effective. OBJECTIVES: This study aimed to better characterize the state of
      the epidermis in dandruff and to determine how a defined set of skin surface
      biomarkers of this state change during a successful course of treatment with a
      potentiated zinc pyrithione (ZPT) shampoo. METHODS: A population of dandruff
      sufferers was treated for 3 weeks with a commercial ZPT shampoo or a non
      medicated product, and the effect of treatment on adherent scalp flake (ASF)
      scores was evaluated. Biopsies were taken from lesional sites at baseline and at
      the end of the study for histomorphometric and histopathologic analysis. Stratum
      corneum (SC) samples were likewise obtained for evaluation of biochemical markers
      of inflammation (IL-1alpha, IL-1RA, IL-8) and barrier integrity (keratin 1, 10,
      11; involucrin; SC lipids; human serum albumin). The biomarker profile was
      evaluated first by comparison with that in non-dandruff subjects at baseline, and
      then to determine whether any treatment-induced changes were correlated with
      reductions in flaking in dandruff sufferers. RESULTS: Taken together, our studies
      showed that treatment with the ZPT shampoo led to an improvement in the overall
      scalp condition as assessed by the resolution of flaking, reduction in epidermal
      thickness and inflammatory biomarkers, and a dramatic improvement in biomarkers
      of epidermal barrier integrity. CONCLUSIONS: The combination of biomarkers
      examined appears to be a good overall descriptor of the health of the scalp in
      dandruff, and changes in these biomarkers track with tissue-level events that
      underlie clinical efficacy in the treatment of dandruff by ZPT shampoo. For the
      first time, we demonstrate a set of tools that extend beyond flaking scores to
      provide insight into specific biological changes occurring on the scalp to enable
      an objective assessment of scalp health.

PMID- 21182511
TI  - How pharmacogenomics of biological response modifiers will influence clinical
      response and toxicity in dermatology.
AB  - Biological response modifiers (BRMs) have dramatically changed therapeutic
      approaches in dermatology. Pharmacogenomic studies are increasingly integral to
      the early development phases of targeted therapies. The first evidence supporting
      the impact that genetic background has on responses to BRMs was from rituximab,
      where the clinical response was correlated with Fc-gamma receptor gene
      polymorphisms. Later, many studies were done to investigate the impact of gene
      polymorphism on the mechanism of action of BRMs. Growing evidence supports the
      view that both efficacy and toxicity of BRMs can be highly influenced by genetic
      background. The foreseeable objective is to select personalized therapeutics,
      based on genetics characteristics that will result in more efficient and less
      toxic treatment. We review the current data focusing on the BRMs widely used in
      the practice of dermatology.

PMID- 21182513
TI  - Re: AlKhodair R, Al-Khenaizan S. Fish tank granuloma: misdiagnosed as cutaneous
      leishmaniasis. Int J Dermatol 2010, 49: 53-55.

PMID- 21182516
TI  - 14(th) Annual Meeting, Cosmetic Dermatology Society of India, Mumbai, September
      2010.

PMID- 21182515
TI  - Comment on: Kikuchi et al. (Int J Dermatol 2010; 49: 346-348).

PMID- 21182517
TI  - Sociedad Dermatologica de Puerto Rico Congress, Vieques, November 4-7, 2010.

PMID- 21182519
TI  - Drivers of age-specific survival in a long-lived seabird: contributions of
      observed and hidden sources of heterogeneity.
AB  - 1. We assessed the relative influence of variability in recruitment age, dynamic
      reproductive investment (time-specific reproductive states) and frailty
      (unobserved differences in survival abilities across individuals) on survival in
      the black-legged kittiwake. Furthermore, we examined whether observed variability
      in survival trajectories was best explained by immediate reproductive investment,
      cumulative investment, or both. 2. Individuals that delayed recruitment (>= age
      7) suffered a higher mortality risk than early recruits (age 3), especially later
      in life, suggesting that recruitment age may be an indicator of individual
      quality. Although recruitment age helped explain variation in survival, time
      varying reproductive investment had a more substantial influence. 3. The
      dichotomy of attempting to breed or not explained variability in survival across
      life better than other parameterizations of reproductive states such as clutch
      size, brood size or breeding success. In the kittiwake, the sinequanon condition
      to initiate reproduction is to hold a nest site, which is considered a very
      competitive activity. This might explain why attempting to breed is the key level
      of investment that affects survival, independent of the outcome (failure or
      success). 4. Interestingly, the more individuals cumulate reproductive attempts
      over life, the lower their mortality risk, indicating that breeding experience
      may be a good indicator of parental quality as well. In contrast, attempting to
      breed at time t increased the risk of mortality between t and t + 1. We thus
      detected an immediate trade-off between attempting to breed and survival in this
      population; however, the earlier individuals recruited, and the more breeding
      experience they accumulated, the smaller the cost. 5. Lastly, unobserved
      heterogeneity across individuals improved model fit more (1.3 times) than fixed
      and dynamic sources of observed heterogeneity in reproductive investment,
      demonstrating that it is critical to account for both sources of individual
      heterogeneity when studying survival trajectories. Only after simultaneously
      accounting for both sources of heterogeneity were we able to detect the 'cost' of
      immediate reproductive investment on survival and the 'benefit' of cumulative
      breeding attempts (experience), a proxy to individual quality.

PMID- 21182520
TI  - Developmental plasticity of immune defence in two life-history ecotypes of the
      garter snake, Thamnophis elegans - a common-environment experiment.
AB  - 1. Ecoimmunological theory predicts a link between life-history and immune
      defence strategies such that fast-living organisms should rely more on
      constitutive innate defences compared to slow-living organisms. An untested
      assumption of this hypothesis is that the variation in immune defence associated
      with variation in life history has a genetic basis. 2. Replicate populations of
      two life-history ecotypes of the garter snake Thamnophis elegans provide an ideal
      system in which to test this assumption. Free-ranging snakes of the fast-living
      ecotype, which reside in lakeshore habitats, show higher levels of three measures
      of constitutive innate immunity than those of the slow-living ecotype, which
      inhabit meadows around the lake. Although this pattern is consistent with the
      ecoimmunological pace-of-life hypothesis, environmental differences between the
      lakeshore and meadow habitats could also explain the observed differences in
      immune defence. 3. We performed a common-environment experiment to distinguish
      between these alternatives. Snakes born and raised in common-environment
      conditions reflected the immune phenotype of their native habitats when sampled
      at 4 months of age (i.e. fast-living lakeshore snakes showed higher levels of
      natural antibodies, complement activity and bactericidal competence than slow
      living meadow snakes), but no longer showed differences when 19 months old. 4.
      This suggests that the differences in innate immunity observed between the two
      ecotypes have an important - and likely age-specific - environmental influence,
      with these immune components showing developmental plasticity. A genetic effect
      in early life may also be present, but further research is needed to confirm this
      possibility and therefore provide a more definitive test of the ecoimmunological
      pace-of-life hypothesis in this system.

PMID- 21182521
TI  - Prey, predators, parasites: intraguild predation or simpler community modules in
      disguise?
AB  - 1. Competition and predation are at the heart of community ecology. The
      theoretical concept of intraguild predation (IGP) combines these key interactions
      in a single community module. Because IGP is believed to be ubiquitous in nature,
      it has been subject to extensive research, and there exists a well-developed
      theoretical framework. 2. We show that a general class of IGP models can be
      transformed to simpler, but equivalent community structures. This rather
      unexpected simplification depends critically on the property of 'indiscriminate
      predation', which we define broadly as the top-predator not distinguishing
      between its two different prey species. 3. In a broader context, the great
      importance of IGP and of the simplifying transformation we report here is
      enhanced by the recent insight that the basic IGP structure extends naturally to
      host-parasitoid and host-pathogen communities. We show that parasites infecting
      prey (predators) tend to render IGP effectively into exploitative competition
      (tritrophic food chain, respectively). 4. The equivalence between the original
      and simplified community module makes it possible to take advantage from already
      existing insights. We illustrate this by means of an eco-epidemiological IGP
      model that is strikingly similar to a classical exploitative competition model.
      5. The change of perspective on certain community modules may contribute to a
      better understanding of food web dynamics. In particular, it may help explain the
      interactions in food webs that include parasites. Given the ubiquity of
      parasitism, food webs may appear in a different light when they are transformed
      to their simplified analogue.

PMID- 21182522
TI  - Individual differences in reproductive costs examined using multi-state methods.
AB  - 1. Trade-offs among life-history traits are common because individuals have to
      partition limited resources between multiple traits. Reproductive costs are
      generally assumed to be high, resulting in reduced survival and fecundity in the
      following year. However, it is common to find positive rather than negative
      correlations between life-history traits. 2. Here, we use a data set from the
      individual-based study of red deer on the Isle of Rum to examine how these costs
      vary between individuals and at different ages, using multi-state mark-recapture
      methodology. 3. Females that had reproduced frequently in the past incurred lower
      costs of reproduction in terms of survival in the following year and were more
      likely to reproduce in two consecutive years. Older individuals and those that
      had not reproduced frequently exhibited higher costs. 4. These results highlight
      the importance of considering heterogeneity and individual quality when examining
      trade-offs and demonstrate the effectiveness of using detailed long-term data
      sets to explore life-history strategies using multi-state mark-recapture models.

PMID- 21182523
TI  - Human dental age estimation by calculation of pulp-tooth volume ratios yielded on
      clinically acquired cone beam computed tomography images of monoradicular teeth.
AB  - Secondary dentine is responsible for a decrease in the volume of the dental pulp
      cavity with aging. The aim of this study is to evaluate a human dental age
      estimation method based on the ratio between the volume of the pulp and the
      volume of its corresponding tooth, calculated on clinically taken cone beam
      computed tomography (CBCT) images from monoradicular teeth. On the 3D images of
      111 clinically obtained CBCT images (Scanora((r)) 3D dental cone beam unit) of 57
      female and 54 male patients ranging in age between 10 and 65 years, the pulp
      tooth volume ratio of 64 incisors, 32 canines, and 15 premolars was calculated
      with Simplant((r)) Pro software. A linear regression model was fit with age as
      dependent variable and ratio as predictor, allowing for interactions of specific
      gender or tooth type. The obtained pulp-tooth volume ratios were the strongest
      related to age on incisors.

PMID- 21182524
TI  - Characterization of the kynurenine pathway in NSC-34 cell line: implications for
      amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is the most common type of motor neuron
      degenerative disease for which the aetiology is still unknown. The kynurenine
      pathway (KP) is a major degradative pathway of tryptophan ultimately leading to
      the production of NAD(+) and is also one of the major regulatory mechanisms of
      the immune response. The KP is known to be involved in several neuroinflammatory
      disorders. Among the KP intermediates, quinolinic acid (QUIN) is a potent
      excitotoxin, while kynurenic acid and picolinic acid are both neuroprotectant.
      This study aimed to (i) characterize the components of the KP in NSC-34 cells (a
      rodent motor neuron cell line) and (ii) assess the effects of QUIN on the same
      cells. RT-PCR and immunocytochemistry were used to characterize the KP enzymes,
      and lactate dehydrogenase (LDH) test was used to assess the effect of QUIN in the
      absence and presence of NMDA receptor antagonists, kynurenines and 1-methyl
      tryptophan. Our data demonstrate that a functional KP is present in NSC-34 cells.
      LDH tests showed that (i) QUIN toxicity on NSC-34 cells increases with time and
      concentration; (ii) NMDA antagonists, 2-amino-5-phosphonopentanoic acid, MK-801
      and memantine, can partially decrease QUIN toxicity; (iii) kynurenic acid can
      decrease LDH release in a linear manner, whereas picolinic acid does the same but
      non-linearly; and (iv) 1-methyl tryptophan is effective in decreasing QUIN
      release by the rodent microglial cell line BV-2 and thus protects NSC-34 from
      cell death. There is currently a lack of effective treatment for ALS and our in
      vitro results provide a novel therapeutic strategy for ALS patients.

PMID- 21182525
TI  - Inhibition of cPLA2 activation by Ginkgo biloba extract protects spinal cord
      neurons from glutamate excitotoxicity and oxidative stress-induced cell death.
AB  - Ginkgo biloba extract (EGb761) has been shown to be neuroprotective; however, the
      mechanism by which EGb761 mediates neuroprotection remains unclear. We
      hypothesized that the neuroprotective effect of EGb761 is mediated by inhibition
      of cytosolic phospholipase A(2) (cPLA(2)), an enzyme that is known to play a key
      role in mediating secondary pathogenesis after acute spinal cord injury (SCI). To
      determine whether EGb761 neuroprotection involves the cPLA(2) pathway, we first
      investigated the effect of glutamate and hydrogen peroxide on cPLA(2) activation.
      Results showed that both insults induced an increase in the expression of
      phosphorylated cPLA(2) (p-cPLA(2)), a marker of cPLA(2) activation, and neuronal
      death in vitro. Such effects were significantly reversed by EGb761
      administration. Additionally, EGb761 significantly decreased prostaglandin E(2)
      (PGE(2)) release, a downstream metabolite of cPLA(2). Moreover, inhibition of
      cPLA(2) activity with arachidonyl trifluromethyl ketone improved neuroprotection
      against glutamate and hydrogen peroxide-induced neuronal death, and reversed Bcl
      2/Bax ratio; notably, EGb761 produced greater effects than arachidonyl
      trifluromethyl ketone. Finally, we showed that the extracellular signal-regulated
      kinase 1/2 signaling pathway is involved in EGb761's modulation of cPLA(2)
      phosphorylation. These results collectively suggest that the protective effect of
      EGb761 is mediated, at least in part, through inhibition of cPLA(2) activation,
      and that the extracellular signal-regulated kinase 1/2 signaling pathway may play
      an important role in mediating the EGb761's effect.

PMID- 21182526
TI  - Region-specific regulation of 5-HT1A receptor expression by Pet-1-dependent
      mechanisms in vivo.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) neurotransmission is negatively regulated
      by 5-HT1A autoreceptors on raphe neurons, and is implicated in mood disorders.
      Pet-1/FEV is an ETS transcription factor expressed exclusively in serotonergic
      neurons and is essential for serotonergic differentiation, although its
      regulation of 5-HT receptors has not yet been studied. Here, we show by
      electrophoretic mobility shift assay that recombinant human Pet-1/FEV binds
      directly to multiple Pet-1 elements of the human 5-HT1A receptor promoter to
      enhance its transcriptional activity. In luciferase reporter assays, mutational
      analysis indicated that while several sites contribute, the Pet-1 site at -1406
      bp had the greatest effect on 5-HT1A promoter activity. To address the effect of
      Pet-1 on 5-HT1A receptor regulation in vivo, we compared the expression of 5-HT1A
      receptor RNA and protein in Pet-1 null and wild-type littermate mice. In the
      raphe nuclei of Pet-1-/- mice tryptophan hydroxylase 2 (TPH2) RNA, and 5-HT and
      TPH immunostaining were greatly reduced, indicating a deficit in 5-HT production.
      Raphe 5-HT1A RNA and protein levels were also reduced in Pet-1-deficient mice,
      consistent with an absence of Pet-1-mediated transcriptional enhancement of 5
      HT1A autoreceptors in serotonergic neurons. Interestingly, 5-HT1A receptor
      expression was up-regulated in the hippocampus, but down-regulated in the
      striatum and cortex. These data indicate that, in addition to transcriptional
      regulation by Pet-1 in raphe neurons, 5-HT1A receptor expression is regulated
      indirectly by alterations in 5-HT neurotransmission in a region-specific manner
      that together may contribute to the aggressive/anxiety phenotype observed in Pet
      1 null mice.

PMID- 21182527
TI  - Evidence of a universal scaling relationship for leaf CO2 drawdown along an
      aridity gradient.
AB  - The leaf carbon isotope ratio (delta(13) C) of C3 plants is inversely related to
      the drawdown of CO2 concentration during photosynthesis, which increases towards
      drier environments. We aimed to discriminate between the hypothesis of universal
      scaling, which predicts between-species responses of delta(13) C to aridity
      similar to within-species responses, and biotic homoeostasis, which predicts
      offsets in the delta(13) C of species occupying adjacent ranges. The Northeast
      China Transect spans 130-900 mm annual precipitation within a narrow latitude and
      temperature range. Leaves of 171 species were sampled at 33 sites along the
      transect (18 at >= 5 sites) for dry matter, carbon (C) and nitrogen (N) content,
      specific leaf area (SLA) and delta(13) C. The delta(13) C of species generally
      followed a common relationship with the climatic moisture index (MI). Offsets
      between adjacent species were not observed. Trees and forbs diverged slightly at
      high MI. In C3 plants, delta(13) C predicted N per unit leaf area (Narea) better
      than MI. The delta(13) C of C4 plants was invariant with MI. SLA declined and
      Narea increased towards low MI in both C3 and C4 plants. The data are consistent
      with optimal stomatal regulation with respect to atmospheric dryness. They
      provide evidence for universal scaling of CO2 drawdown with aridity in C3 plants.

PMID- 21182528
TI  - Cytoskeletal dynamics in interphase, mitosis and cytokinesis analysed through
      Agrobacterium-mediated transient transformation of tobacco BY-2 cells.
AB  - Transient transformation with Agrobacterium is a widespread tool allowing rapid
      expression analyses in plants. However, the available methods generate expression
      in interphase and do not allow the routine analysis of dividing cells. Here, we
      present a transient transformation method (termed 'TAMBY2') to enable cell
      biological studies in interphase and cell division. Agrobacterium-mediated
      transient gene expression in tobacco BY-2 was analysed by Western blotting and
      quantitative fluorescence microscopy. Time-lapse microscopy of cytoskeletal
      markers was employed to monitor cell division. Double-labelling in interphase and
      mitosis enabled localization studies. We found that the transient transformation
      efficiency was highest when BY-2/Agrobacterium co-cultivation was performed on
      solid medium. Transformants produced in this way divided at high frequency. We
      demonstrated the utility of the method by defining the behaviour of a previously
      uncharacterized microtubule motor, KinG, throughout the cell cycle. Our analyses
      demonstrated that TAMBY2 provides a flexible tool for the transient
      transformation of BY-2 with Agrobacterium. Fluorescence double-labelling showed
      that KinG localizes to microtubules and to F-actin. In interphase, KinG
      accumulates on microtubule lagging ends, suggesting a minus-end-directed function
      in vivo. Time-lapse studies of cell division showed that GFP-KinG strongly labels
      preprophase band and phragmoplast, but not the metaphase spindle.

PMID- 21182529
TI  - Association genetics of complex traits in plants.
AB  - Association mapping is rapidly becoming the main method for dissecting the
      genetic architecture of complex traits in plants. Currently most association
      mapping studies in plants are preformed using sets of genes selected to be
      putative candidates for the trait of interest, but rapid developments in genomics
      will allow for genome-wide mapping in virtually any plant species in the near
      future. As the costs for genotyping are decreasing, the focus has shifted towards
      phenotyping. In plants, clonal replication and/or inbred lines allows for
      replicated phenotyping under many different environmental conditions. Reduced
      sequencing costs will increase the number of studies that use RNA sequencing data
      to perform expression quantitative trait locus (eQTL) mapping, which will
      increase our knowledge of how gene expression variation contributes to phenotypic
      variation. Current population sizes used in association mapping studies are
      modest in size and need to be greatly increased if mutations explaining less than
      a few per cent of the phenotypic variation are to be detected. Association
      mapping has started to yield insights into the genetic architecture of complex
      traits in plants, and future studies with greater genome coverage will help to
      elucidate how plants have managed to adapt to a wide variety of environmental
      conditions.

PMID- 21182530
TI  - Photoreduction and ketone-sensitized reduction of alkaloids.
AB  - The photoprocesses of berberine, palmatine, coralyne, sanguinarine,
      flavopereirine and ellipticine were studied in several solvents. The quantum
      yields Phi(Delta) of singlet molecular oxygen formation of berberine, palmatine
      and sanguinarine are moderate in dichloromethane (0.2-0.6) and much smaller in
      acetonitrile or trifluoroethanol. For the other alkaloids examined, Phi(Delta) is
      rather independent of solvent polarity. The direct and ketone-sensitized
      photolysis, using steady-state irradiation at 313 nm or 248/308 nm laser pulses,
      was studied by absorption and fluorescence spectroscopy. Thereby, radicals were
      observed yielding eventually dihydro derivatives as major products, which are
      thermally back-converted on admission of oxygen. The quantum yield of conversion
      of alkaloids to dihydroalkaloids is enhanced in the presence of triethylamine.
      The reaction in the presence of ketones and electron or H-atom donors has a
      quantum yield of close to unity.

PMID- 21182531
TI  - Timeframes of UVA-induced bystander effects in human keratinocytes.
AB  - The bystander effect is defined as the induction of cellular damage in
      unirradiated cells, induced by irradiated cells in the surrounding area. Our
      laboratory has previously identified that an environmentally relevant dose of UVA
      is able to induce the effect in human keratinocytes and fibroblasts, seen as
      reduced clonogenic survival. Here we report on our investigations into the
      periods over which the bystander signals are released by the irradiated cells and
      for how long unirradiated cells need to be exposed to them for the effect to be
      induced. Using a coincubation system we have identified that irradiated cells do
      not release the signals immediately following irradiation but have a time lag of
      over 24 h before levels are sufficient to induce the effect, with the signals
      being released for a minimum of 3 days following irradiation. We have also found
      that the recipient cells only require at most 24 h of exposure to these signals
      for induction of the effect. These data indicate that a single exposure to UVA
      can exert an effect for several days postirradiation, thus amplifying the
      deleterious effects of exposure.

PMID- 21182533
TI  - Alcohol research: past, present, and future.
AB  - Created forty years ago, the National Institute on Alcohol Abuse and Alcoholism
      (NIAAA) has played a major role in the great strides made in the understanding,
      treatment, prevention, and public acceptance of alcohol-use disorders. Throughout
      most of U.S. history "habitual drunkenness" was viewed as a problem of moral
      degeneracy or character flaw inherent in the individual. However, the wealth of
      scientific evidence amassed throughout NIAAA's history has established alcoholism
      as a medical condition, that is, as a disease for which affected individuals
      should feel no shame or be treated with disdain. We look at the developments in
      alcohol epidemiology, typology, etiology, prevention, and treatment research over
      the past 40 years. We also discuss how NIAAA addresses alcohol disorders from a
      life-course framework, affecting all stages of the lifespan, from fetus through
      child, adolescent, and young adult, to midlife/senior adult, with each stage
      involving different risks, consequences, prevention efforts, and treatment
      strategies.

PMID- 21182532
TI  - Blood donations from previously transfused or pregnant donors: a multicenter
      study to determine the frequency of alloexposure.
AB  - BACKGROUND: Transfusion-related acute lung injury (TRALI) mitigation strategies
      include the deferral of female donors from apheresis platelet (PLT) donations and
      the distribution of plasma for transfusion from male donors only. We studied the
      implications of these policies in terms of component loss at six blood centers in
      the United States. STUDY DESIGN AND METHODS: We collected data from allogeneic
      blood donors making whole blood and blood component donations during calendar
      years 2006 through 2008. We analyzed the distribution of donations in terms of
      the sex, transfusion and pregnancy histories, and blood type. RESULTS: A TRALI
      mitigation policy that would not allow plasma from female whole blood donors to
      be prepared into transfusable plasma components would result in nearly a 50%
      reduction in the units of whole blood available for plasma manufacturing and
      would decrease the number of type AB plasma units that could be made from whole
      blood donations by the same amount. Deferral of all female apheresis PLT donors,
      all female apheresis PLT donors with histories of prior pregnancies, or all
      female apheresis PLT donors with histories of prior pregnancies and positive
      screening test results for antibodies to human leukocyte antigens (HLAs) will
      result in a loss of 37.1, 22.5, and 5.4% of all apheresis PLT donations,
      respectively. CONCLUSION: A TRALI mitigation policy that only defers female
      apheresis PLT donors with previous pregnancies and HLAs would result in an
      approximately 5% decrease in the inventory of apheresis PLTs, but would eliminate
      a large proportion of components that are associated with TRALI.

PMID- 21182534
TI  - Alcoholic liver disease and exacerbation by malnutrition and infections: what
      animal models are currently available?
AB  - Alcoholic liver disease remains a frequent and serious problem for increasing
      numbers of patients. Research has expanded our molecular understanding of the
      cellular basis of disease progression; however, translation into therapy is still
      hampered by a lack of suitable animal models for alcoholic liver disease, as well
      as from consequences of related liver damage due to malnutrition, hepatitis C
      virus infection, or abuse of other substances. Many patients with liver disease
      do not simply consume too much alcohol; they also suffer from comorbidities such
      as obesity or viral hepatitis, and/or may be addicted to other drugs besides
      alcohol. This review will summarize the currently available animal models to
      study liver disease due to either single causes or combinations of liver toxic
      substances/infections and alcohol.

PMID- 21182536
TI  - Programming of the renin response to haemorrhage by mild maternal renal
      impairment in sheep.
AB  - 1. The aim of the present study was to test the hypothesis that the renin
      response to mechanisms activated by haemorrhage is programmed by exposure to
      maternal renal dysfunction. 2. In 26-27-day-old lambs born to ewes that had
      reduced renal function (STNxL, n=10) and lambs born to ewes with normal renal
      function (ConL, n=6), 1.6 mL/kg per min of blood was removed over 10 min. 3.
      Under basal conditions, the STNxL group had increased mean arterial pressure (P <
      0.05). In response to haemorrhage, mean arterial pressure decreased in the STNxL
      group (P < 0.001), but there was no significant change in the ConL group. 4.
      Although plasma renin level increased in both groups (P < 0.05), the peak
      response was reduced and delayed in the STNxL group. In contrast, the rise in
      arginine vasopressin (AVP) level was similar in both groups and occurred over the
      same time course. At 24 h, both plasma renin and AVP level were the same as those
      measured before haemorrhage in both groups. Kidney renin level was similar in the
      two groups. 5. The attenuated renin response to haemorrhage in the STNxL group
      might explain the inability to maintain arterial pressure after haemorrhage. The
      results of the present study suggest that the renin response of the postnatal
      kidney to reductions in blood volume can be affected by the intrauterine
      environment. If these changes persist into adulthood, it suggests that permanent
      programming has occurred. Thus, the ability of an individual to respond to acute
      severe reductions in blood volume might be determined during intrauterine life.

PMID- 21182537
TI  - Cytological analysis of mycelial incompatibility in Helicobasidium mompa.
AB  - When the mycelia of Helicobasidium mompa encounter mycelia with a different
      genetic background, distinct demarcation lines form. The hyphae of H. mompa
      induce heterogenic incompatibility accompanied by active programmed cell death
      (PCD) process. In this study, we observed hyphal interaction between compatible
      and incompatible H. mompa pairs by means of light and electron microscopy. PCD
      started with one of the two approaching hyphae. Heterochromatin condensation and
      genomic DNA laddering were not observed. Moreover, cell damage began with the
      tonoplast and continued with the plasma membrane and nuclear membrane, suggesting
      that the PCD observed in heterogenic incompatibility of H. mompa is a vacuole
      mediated process.

PMID- 21182535
TI  - Human category learning 2.0.
AB  - During the 1990s and early 2000s, cognitive neuroscience investigations of human
      category learning focused on the primary goal of showing that humans have
      multiple category-learning systems and on the secondary goals of identifying key
      qualitative properties of each system and of roughly mapping out the neural
      networks that mediate each system. Many researchers now accept the strength of
      the evidence supporting multiple systems, and as a result, during the past few
      years, work has begun on the second generation of research questions-that is, on
      questions that begin with the assumption that humans have multiple category
      learning systems. This article reviews much of this second generation of
      research. Topics covered include (1) How do the various systems interact? (2) Are
      there different neural systems for categorization and category representation?
      (3) How does automaticity develop in each system? and (4) Exactly how does each
      system learn?

PMID- 21182538
TI  - Flux-based analysis of sulfur metabolism in desulfurizing strains of Rhodococcus
      erythropolis.
AB  - Rhodococcus erythropolis has been studied widely for potential applications in
      biodesulfurization. Previous works have been largely experimental with an
      emphasis on the characterization and genetic engineering of desulfurizing strains
      for improved biocatalysis. A systems modeling approach that can complement these
      experimental efforts by providing useful insights into the complex interactions
      of desulfurization reactions with various other metabolic activities is absent in
      the literature. In this work, we report the first attempt at reconstructing a
      flux-based model to analyze sulfur utilization by R. erythropolis. The model
      includes the 4S pathway for dibenzothiophene (DBT) desulfurization. It predicts
      closely the growth rates reported by two independent experimental studies, and
      gives a clear and comprehensive picture of the pathways that assimilate the
      sulfur from DBT into biomass. In addition, it successfully elucidates that
      sulfate promotes higher cell growth than DBT and its presence in the medium
      reduces DBT desulfurization rates. A study using eight carbon sources suggests
      that ethanol and lactate yield higher cell growth and desulfurization rates than
      citrate, fructose, glucose, gluconate, glutamate, and glycerol.

PMID- 21182539
TI  - Genome-wide phylogenetic analysis of Gluconobacter, Acetobacter, and
      Gluconacetobacter.
AB  - Phylogenetic relationships among three genera, Gluconobacter, Acetobacter, and
      Gluconacetobacter, of acetic acid bacteria (AAB) are still unclear, although
      phylogenetic analysis using 16S rRNA gene sequence has shown that
      Gluconacetobacter diverged first from the ancestor of these three genera.
      Therefore, the relationships among these three genera were investigated by genome
      wide phylogenetic analysis of AAB. Contrary to the results of 16S rRNA gene
      analysis, phylogenetic analysis of 293 enzymes involved in metabolism clearly
      showed that Gluconobacter separated first from its common ancestor with
      Acetobacter and Gluconacetobacter. In addition, we defined 753 unique orthologous
      proteins among five known complete genomes of AAB, and phylogenetic analysis was
      carried out using concatenated gene sequences of these 753 proteins. The result
      also showed that Gluconobacter separated first from its common ancestor with
      Acetobacter and Gluconacetobacter. Our results strongly suggest that
      Gluconobacter was the first to diverge from the common ancestor of Gluconobacter,
      Acetobacter, and Gluconacetobacter, a relationship that is in good agreement with
      the physiologies and habitats of these genera.

PMID- 21182540
TI  - Microorganisms form exocellular structures, trophosomes, to facilitate
      biodegradation of oil in aqueous media.
AB  - Cytochemical staining and microscopy were used to study the trophic structures
      and cellular morphotypes that are produced during the colonization of oil-water
      interfaces by oil-degrading yeasts and bacteria. Among the microorganisms studied
      here, the yeasts (Schwanniomyces occidentalis, Torulopsis candida, Candida
      tropicalis, Candida lipolytica, Candida maltosa, Candida paralipolytica) and two
      representative bacteria (Rhodococcus sp. and Pseudomonas putida) produced
      exocellular structures composed of biopolymers during growth on petroleum
      hydrocarbons. Four of the yeasts including S. occidentalis, T. candida, C.
      tropicalis and C. maltosa excreted polymers through modified sites in their cell
      wall ('canals'), whereas C. lipolytica and C. paralipolytica and the two
      bacterial species secreted polymers over the entire cell surface. These polymers
      took the form of fibrils and films that clogged pores and cavities on the
      surfaces of the oil droplets. A three-dimensional reconstruction of the cavities
      using serial thin sections showed that the exopolymer films isolated the ambient
      aqueous medium together with microbial cells and oil to form both closed and open
      granules that contained pools of oxidative enzymes utilized for the degradation
      of the oil hydrocarbons. The formation of such granules, or 'trophosomes,'
      appears to be a fundamental process that facilitates the efficient degradation of
      oil in aqueous media.

PMID- 21182541
TI  - New alternative in treatment of callus.
AB  - The pathological transformation of the skin into a thick and hard callus due to
      repetitive trauma or friction is commonly known as corn. Although a variety of
      medical and operative treatment choices have been proposed, an ideal treatment
      method is yet to be defined. Effectiveness of tangential excision together with
      topical cantharidin has been evaluated. We used Canthacur-PS as an adjunct to
      excision in an outpatient setting. Canthacur-PS is a commercially available
      topical solution that includes 1% cantharidin, 30% salicylic acid and 5%
      podophyllin. The treatment has been applied to 72 patients. We found that 65
      patients (90.3%) had corn on their feet and seven patients (9.7%) on their hands.
      Thick, hard and hyperkeratotic skin area was scraped with the help of a no. 15
      blade. The solution was applied on and around the periphery (up to 1-2 mm) of the
      lesion with a cotton swab, and kept closed for 5 days with an antibiotic
      dressing. All the patients had been followed up for at least 1 year and evaluated
      by clinical examination and patient satisfaction query. One session of treatment
      succeeded in 57 (79.2%) corn patients. Two sessions in nine corn patients
      (12.5%), three sessions in five corn patients (6.9%) and four sessions in one
      patient (1.4%) were needed. Only one recurrence (1.4%) was seen. No scar
      formation or other side-effects were seen. Our findings show that this treatment
      method is a simple, minimally invasive and reliable treatment for calluses.

PMID- 21182542
TI  - Single nucleotide polymorphism at exon 7 splice acceptor site of OAS1 gene
      determines response of hepatitis C virus patients to interferon therapy.
AB  - BACKGROUND AND AIM: Response to interferon therapy and disease progression in
      hepatitis C virus (HCV) infected patients differs among individuals, suggesting a
      possibility of a contribution of host genetic factors. 2'-5'-oligoadenylate
      synthetase 1 (OAS1), an important component of the innate immune system with a
      proven antiviral function, may therefore have a relationship with the response to
      interferon therapy and clinical course of HCV disease. Our aim was to determine
      the frequency of single nucleotide polymorphism (SNP) at exon 7 splice acceptor
      site (SAS) of the OAS1 gene in relation to the interferon response and status of
      HCV infection. METHODS: A 203 bp fragment containing exon 7 SAS was amplified in
      70 HCV chronic patients and 50 healthy controls. SNP was examined using
      restriction fragment length polymorphism (RFLP) genotyping method. Correlations
      of SNP genotypes with response to interferon and clinical status of patients were
      statistically analyzed. RESULTS: There was an increasing trend of response from
      AA to AG to GG genotypes (P = 0.007). Genotype AA was associated with non
      response to interferon and higher degree of liver fibrosis (P = 0.05).
      Multivariate analysis showed this SNP as independent and a significant
      determinant of the outcome of interferon therapy (odds ratio 4.913 [95%
      confidence interval 1.365-8.2], P = 0.006). CONCLUSIONS: This is the first study
      to show a significant association between the functional SNP at exon 7 SAS of
      OAS1 gene and the viral response to interferon in chronic HCV patients. Patients
      with AA genotype were associated with progressive HCV disease and viral
      resistance to interferon therapy. This OAS SNP is a potential bio-marker to
      predict IFN response in chronic hepatitis C patients.

PMID- 21182543
TI  - Prevalence of celiac disease in the northern part of India: a community based
      study.
AB  - BACKGROUND AND AIM: While celiac disease is estimated to affect about 1% of the
      world's population, it is thought to be uncommon not only in India but in Asia
      also. There is a lack of studies on the prevalence of celiac disease from Asian
      nations. The aim of the present study was to estimate the prevalence of celiac
      disease in the community. METHODS: In a cross sectional study, we estimated the
      prevalence of celiac disease in urban and rural populations in the National
      Capital Region, Delhi, India. A structured questionnaire was administered, by
      door-to-door visits, to all participants to collect socio-demographic data and to
      screen for features of celiac disease, namely chronic or recurrent diarrhea and,
      anemia. In children, additional features, namely short stature (linear height
      below 5th percentile for age) and failure to thrive/gain weight were also used.
      All respondents who were screen positive (any one of above) and 10% of screen
      negative individuals were called for serological testing, which is anti-tissue
      transglutaminase antibody. All serologically positive respondents were invited to
      undergo further evaluation including endoscopic biopsy. Celiac disease was
      diagnosed on the basis of a positive serology, the presence of villous atrophy
      and/or response to gluten free diet. RESULT: Among 12,573 contacted, 10,488
      (83.4%) (50.6% male) agreed to participate. Based on screening, 5622 (53.6%)
      participants were screen positive. Of all those screen positive, 2167 (38.5%)
      agreed for serological testing; additionally 712 (14%) negatives were also
      tested. The overall sero-prevalence of celiac disease was 1.44% (95% confidence
      interval [CI] 1.22 1.69) and the overall prevalence of celiac disease was 1.04%
      (95% CI 0.85 1.25). CONCLUSION: The prevalence of celiac disease in this north
      Indian community is 1 in 96. Celiac disease is more common than is recognized in
      India.

PMID- 21182544
TI  - Comparison of computed tomography and routine radiography of the tympanic bullae
      in the diagnosis of otitis media in the calf.
AB  - BACKGROUND: Otitis media is difficult to diagnose antemortem. Case reports have
      described computed tomography (CT) in the diagnosis, but not all cases were
      confirmed. HYPOTHESIS: CT is a sensitive and specific imaging modality of the
      tympanic bullae and can be used as the gold standard for the diagnosis of otitis
      media. ANIMALS: Sixteen Holstein calves 5-7 weeks of age were included. METHODS:
      Prospective study. All calves were sedated with i.v. xylazine (0.05-0.15 mg/kg)
      for routine radiography (3 views) and CT of the tympanic bullae followed by
      necropsy. RESULTS: Based upon necropsy findings, 10 of 16 calves were affected
      with otitis media, 4 unilaterally and 6 bilaterally. Imaging changes associated
      with otitis media included increased soft tissue opacity within the bulla,
      thickening of the bulla wall, enlarged bulla, and osteolysis of the bulla wall
      and trabeculations. The most frequent radiographic changes were lysis of
      trabeculations and increased soft tissue opacity, which were present in 56.3% of
      affected bullae. On CT, increased soft tissue opacity within the bulla was
      present in 93.8% of affected bullae. Sensitivity of radiography and CT was 68.8
      and 93.8% and specificity was 50 and 100%, respectively. The kappa value between
      radiography and CT with necropsy diagnosis was 0.19 for radiography, indicating
      poor agreement, and 0.94 for CT, indicating excellent agreement. CONCLUSION: CT
      is more specific, more sensitive, and easier to interpret than radiography and
      can be used as the gold standard in the diagnosis of otitis media in the calf.

PMID- 21182545
TI  - Diversity of plasmids and transmission of high-level mupirocin mupA resistance
      gene in Staphylococcus haemolyticus.
AB  - The coagulase-negative staphylococci are known for their ability to acquire
      resistance genes, which limits the choice of therapeutic options for the
      treatment of infections caused by these microorganisms. In this study, the
      diversity of high-level mupirocin resistance plasmids (Mup(R) ) was investigated
      in four strains of Staphylococcus haemolyticus belonging to different pulsed
      field gel electrophoresis (PFGE) types or subtypes, isolated in a Brazilian
      hospital. These strains harbor the mupA gene in large plasmids. In addition, the
      presence of IS257 sequences flanking the mupA gene was also shown. Two isolates
      belonging to two different PFGE types exhibited a similar polymorphism for a
      fragment of the mupA gene and the closest proximal flanking copies of the IS257,
      suggesting horizontal transmission of S. haemolyticus mupirocin resistance
      plasmids in the environment and a role of this species as a reservoir of the mupA
      gene.

PMID- 21182546
TI  - Isolation and characterisation of two cDNAs encoding the neuromedin U receptor
      from goldfish brain.
AB  - Intracerebroventricular administration of neuromedin U (NMU) exerts an
      anorexigenic effect in a goldfish model. However, little is known about the NMU
      receptor and its signalling system in fish. In the present study, we isolated and
      cloned two cDNAs encoding different proteins comprising 429 and 388 amino acid
      residues from the goldfish brain based on the nucleotide sequences of human NMU
      receptor 1 (NMU-R1) and receptor 2 (NMU-R2). Hydropathy and phylogenetic analyses
      suggested that these two proteins were orthologues of NMU-R1 and -R2 of goldfish.
      We established two human embryonic kidney 293 cell lines stably expressing
      putative NMU-R1 and -R2, respectively, and showed that NMU induced an increase in
      intracellular calcium concentration ([Ca(2+)](i)) in these cells. We examined the
      presence of NMU-R1 and -R2 in the goldfish brain by western blotting analysis
      using affinity-purified antisera raised against peptide fragments derived from
      these receptors. NMU-R1-specific and NMU-R2-specific antisera detected a 49-kDa
      and 45-kDa immunopositive bands, respectively, in the brain extract. The mass of
      each band corresponded to that of the deduced respective primary structures.
      Reverse transcriptase-polymerase chain reaction analysis showed that NMU-R1 and 
      R2 transcripts were detected in several tissues. In particular, both mRNAs were
      strongly expressed in the goldfish brain. By contrast, NMU-R2 mRNA was also
      expressed in the gut. These results indicate for the first time that NMU-R
      orthologues exist in goldfish, and suggest physiological roles of NMU and its
      receptor system in fish.

PMID- 21182547
TI  - Massive cryptococcal disseminated infection in an immunocompetent cat.

PMID- 21182548
TI  - The association between spending on methamphetamine/amphetamine and cannabis for
      personal use and earnings from acquisitive crime among police detainees in New
      Zealand.
AB  - AIMS: Few studies have examined the statistical association between
      methamphetamine/amphetamine use and acquisitive crime. Both
      methamphetamine/amphetamine and cannabis use have been implicated by New Zealand
      Police as factors in acquisitive offending among active criminal populations. The
      aim of our study was to examine the statistical association between spending on
      methamphetamine/amphetamine and cannabis and earnings from acquisitive crime
      among police detainees in New Zealand. SETTING: Four police stations in different
      regions. PARTICIPANTS: A sample of 2125 police detainees were interviewed about
      their drug use and acquisitive crime. DESIGN: Statistical models were developed
      to predict involvement in acquisitive crime using spending on
      methamphetamine/amphetamine and cannabis for personal use, and to examine
      associations between the level of spending on methamphetamine/amphetamine and
      cannabis for personal use and level of dollar earnings from acquisitive crime.
      MEASUREMENTS: Self-reported spending on drug use and self-reported earnings from
      acquisitive crime in the past 30 days. FINDINGS: Spending on cannabis and
      methamphetamine/amphetamine could predict involvement in acquisitive crime. Level
      of spending on methamphetamine/amphetamine and cannabis was associated positively
      with the level of earnings from property crime. Level of spending on
      methamphetamine/amphetamine was also associated positively with level of earnings
      from drug dealing. There was a largely negative association between level of
      spending on cannabis and level of earnings from drug dealing. CONCLUSIONS: High
      spending on methamphetamine/amphetamine is associated statistically with higher
      earnings from acquisitive crime among police detainees. Further research into
      this association, and in particular the causal nature of the association, is
      required to obtain clear policy recommendations.

PMID- 21182549
TI  - Exploring the emergence of alcohol use disorder symptoms in the two years after
      onset of drinking: findings from the National Surveys on Drug Use and Health.
AB  - AIMS: This study investigates the occurrence of clinical features of alcohol
      dependence and socially maladaptive drinking during the first 24 months after the
      onset of alcohol use. DESIGN: Data for this study are from the nationally
      representative 2004-07 National Surveys on Drug Use and Health (NSDUH). SETTING:
      General population of the United States, aged 12 years and older. PARTICIPANTS:
      New-onset alcohol users (NOAUs) were drinkers who started to drink alcohol within
      24 months of the NSDUH assessment and consumed alcohol during the last 12 months.
      MEASUREMENTS: The NSDUH assessed for clinical features of alcohol dependence and
      socially maladaptive drinking, consistent with the DSM-IV. FINDINGS: NOAUs
      frequently experienced problems relating to self-reported tolerance, spending a
      great deal of time recovering from the effects of alcohol and unsuccessful
      attempts at cutting down on drinking. The likelihood of experiencing the clinical
      features increased steadily in the first 9 months after use, but appeared to
      plateau or only gradually increase thereafter. Strong evidence emerged that the
      clinical features measured a single latent dimensional of 'alcohol use disorder'
      (AUD) in this sample. The majority of the clinical features were good indicators
      of the underlying AUD continuum in the 2 years after first drinking onset.
      CONCLUSIONS: There may be a period of time during the second year of alcohol use,
      when level of alcohol use disorder fluctuates rather than increases. Public
      health and safety efforts designed to target problematic alcohol use in the
      earliest stages of alcohol involvement could be useful in preventing the
      escalation of alcohol problems in this group of drinkers.

PMID- 21182550
TI  - An Ecological Momentary Assessment analysis of relations among coping, affect and
      smoking during a quit attempt.
AB  - AIMS: This study used Ecological Momentary Assessment (EMA) data from smokers
      trying to quit to assess relations among coping, positive affect, negative affect
      and smoking. The effects of stress coping on affect and smoking were examined.
      DESIGN: Data from a randomized clinical trial of smoking cessation treatments
      were submitted to multi-level modeling to test the effects of coping with
      stressful events on subsequent affect and smoking. SETTING: Center for Tobacco
      Research and Intervention, Madison, Wisconsin. PARTICIPANTS: A total of 372 adult
      daily smokers who reported at least one stressful event and coping episode and
      provided post-quit data. MEASUREMENTS: Participants' smoking, coping and affect
      were assessed in near real time with multiple EMA reports using electronic
      diaries pre- and post-quit. FINDINGS: Multi-level models indicated that a single
      coping episode did not predict a change in smoking risk over the next 4 or 48
      hours, but coping in men was associated with concurrent reports of increased
      smoking. Coping predicted improved positive and negative affect reported within 4
      hours of coping, but these affective gains did not predict reduced likelihood of
      later smoking. Pre-quit coping frequency and gender moderated post-quit stress
      coping relations with later positive affect. Men and those with greater pre-quit
      coping frequency reported greater gains in positive affect following post-quit
      coping. CONCLUSIONS: Coping responses early in a quit attempt may help smokers
      trying to quit feel better, but may not help them stay smoke-free.

PMID- 21182551
TI  - Effect of compliance with nicotine gum dosing on weight gained during a quit
      attempt.
AB  - AIM: Using nicotine gum can reduce the amount of weight gained when quitting.
      Here we examine the relationship between weight gain and use of adequate amounts
      of gum. To mitigate the confounders associated with correlational analyses, we
      contrast the effects of active gum and placebo, and analyze outcomes
      prospectively. DESIGN AND SETTING: Randomized double-blind placebo-controlled
      trial of nicotine gum. Participants were instructed to use nine to 15 pieces of
      gum/day for the first 2 months of treatment. PARTICIPANTS: Participants (n = 103)
      were randomized to either active (2 mg or 4 mg) or placebo gum. MEASUREMENTS: We
      examined the effect on weight gain of the interaction between treatment (active
      versus placebo) and daily gum use [>=9 pieces/day (compliant use) versus < 9
      pieces/day]. FINDINGS: After 30 days of abstinence, smokers treated with active
      gum had not gained significantly less weight than those on placebo (1.1 kg versus
      1.6 kg, P = 0.175). However, a significant compliance-treatment interaction was
      observed (P = 0.005): active gum users who used >=9 pieces/day during the first
      14 days of treatment had gained less weight at follow-up (0.6 kg versus 1.6 kg
      for those who used <9 pieces/day, P = 0.017), but participants randomized to the
      placebo group saw no such benefit from compliant use. A similar compliance
      treatment interaction (P = 0.046) was also observed when the effect of compliance
      was examined within active treatment (2 mg versus 4 mg). CONCLUSIONS: When
      smokers are quitting, those who use more pieces of nicotine gum experience less
      weight gain in the first 30 days. This relationship is not seen for smokers on
      placebo gum.

PMID- 21182552
TI  - Outreach screening of drug users for cirrhosis with transient elastography.
AB  - AIMS: Transient elastography (TE) is a non-invasive sensitive tool for diagnosing
      cirrhosis in hospital-based cohorts. This study aimed to evaluate TE as a
      screening tool for cirrhosis among drug users. DESIGN: Cross-sectional study.
      SETTING: All treatment centres in the county of Funen, Denmark. PARTICIPANTS:
      Drug users attending treatment centres during the presence of the study team.
      MEASUREMENTS: Liver stiffness measurements (LSM) by transient elastography using
      the Fibroscan device; blood tests for viral hepatitis, HIV infection and
      hyaluronic acid (HA) levels; and routine liver tests. Individuals with LSM >= 8
      kPa were referred to the hospital for treatment evaluation. Individuals with LSM
      >= 12 kPa were recommended a liver biopsy. FINDINGS: Among 175 drug users
      negative for hepatitis C, 13% had LSM = 8-11.9 kPa and 4% had LSM >= 12 kPa;
      elevated LSM was associated with a body mass index (BMI) > 30. Among 128 drug
      users with chronic hepatitis C, 19.5% had LSM = 8-11.9 kPa and 21.1% had LSM >=
      12 kPa (P < 0.001). Repeat LSM at liver biopsy performed a median 3 months after
      screening showed a significant decrease (<12 kPa) among 30% (six of 20), and this
      was independent of alcohol consumption, BMI, age and gender. In 29 patients where
      liver biopsy was performed a LSM >= 16 kPa predicted cirrhosis with 88.9%
      sensitivity and 90% specificity. CONCLUSIONS: Transient elastography is a
      feasible screening tool for cirrhosis among drug users. Transient elastography
      identifies severe liver fibrosis in a significant proportion of drug users with
      hepatitis C infections but management should not be based on a single elevated
      liver stiffness measurement.

PMID- 21182553
TI  - The population impact of smoke-free workplace and hospitality industry
      legislation on smoking behaviour. Findings from a national population survey.
AB  - AIMS: To study the impact of implementing smoke-free workplace and hospitality
      industry legislation on smoking behaviour. DESIGN, SETTING AND PARTICIPANTS: A
      cross-sectional population survey from 2001 to 2008 (n ~ 18,000 per year) was
      used to assess trends and seasonal patterns in smoking and quitting, and to
      examine whether changes could be observed after the workplace smoking ban in the
      Netherlands in 2004 and the hospitality industry ban in 2008. MEASUREMENTS:
      Outcome measures were smoking prevalence, quit attempts and successful quit
      attempts. Interactions with educational level (socio-economic status) and bar
      visiting (exposure to the hospitality industry ban) were tested. FINDINGS: The
      workplace ban was followed by a decrease in smoking prevalence (OR = 0.91, P <
      0.001), but the hospitality industry ban was not (OR = 0.96, P = 0.127). Both
      bans, especially the workplace ban, were followed by an increase in quit attempts
      and successful quit attempts: workplace ban, OR = 1.31, P < 0.001; OR = 1.49, P <
      0.001; hospitality industry ban, OR = 1.13, P = 0.013; OR = 1.44, P < 0.001. The
      workplace ban had a larger effect on successful quitting among higher-educated
      (OR = 0.35, P < 0.001) than on lower-educated respondents (OR = 0.74, P = 0.052).
      The hospitality industry ban had a larger effect on quit attempts among frequent
      bar visitors (OR = 1.48, P = 0.003) than on non-bar visitors (OR = 0.71, P =
      0.014). CONCLUSIONS: A workplace smoking ban in the Netherlands was followed by
      more changes in smoking and quitting than a hospitality industry ban. The
      hospitality industry ban only appeared to have an impact on quit attempts, and
      not on smoking prevalence.

PMID- 21182554
TI  - Inverse association of the obesity predisposing FTO rs9939609 genotype with
      alcohol consumption and risk for alcohol dependence.
AB  - AIMS: To investigate whether the FTO rs9939609 A allele (a risk factor for
      obesity) is associated with measures of alcohol consumption. DESIGN: Population
      based cross-sectional study and two case-control studies. SETTING: Poland and the
      Warsaw area. PARTICIPANTS: A total of 6584 subjects from the WOBASZ survey and
      two cohorts of alcohol-dependent patients (n = 145 and n = 148). MEASUREMENTS:
      Questionnaire data analysis, rs9939609 typing. FINDINGS: Among individuals
      drinking alcohol, the obesity-associated AA genotype was also associated with
      lower total ethanol consumption [sex-, age- and body mass index (BMI)-adjusted
      difference: 0.21 g/day, P = 0.012] and distinct drinking habits with relatively
      low frequency of drinks but larger volume consumed at a time as evidenced by (i)
      association between AA and frequency/amount of typical drinks (P = 0.023,
      multiple logistic regression analysis); (ii) inverse correlation between AA and
      drink frequency adjusted for drink size (P = 0.007 for distilled spirits, P =
      0.018 for beer); (iii) decreased frequency of AA [odds ratio (OR) = 0.46, P =
      0.0004] among those who drank small amounts of distilled spirits (<= 100 ml at a
      time) but frequently (>= 1-2 times/week). A decrease of AA was also found in both
      cohorts of alcohol-dependent patients versus geographically matched subjects from
      WOBASZ yielding a pooled estimate of OR = 0.59, confidence interval (CI): 0.40
      0.88, P = 0.008. Exploratory analysis showed that those with rs9939609 AA
      reported lower (by 1.22) mean number of cigarettes/day during a year of most
      intense smoking (P = 0.003) and were older at start of smoking by 0.44 years (P =
      0.016). CONCLUSIONS: The FTO AA genotype, independently from its effect on BMI,
      is associated with measures of ethanol consumption and possibly tobacco smoking.

PMID- 21182555
TI  - Predictors and correlates of reduced frequency or cessation of injection drug use
      during a randomized HIV prevention intervention trial.
AB  - AIMS: This study conducted a secondary analysis to examine injection cessation
      and decreasing frequency of injection during a multi-site randomized controlled
      HIV prevention intervention trial that sought to reduce sexual and injection risk
      behavior among young injection drug users. DESIGN AND SETTING: A six-session,
      cognitive-behavioral skills-building intervention in which participants were
      taught peer education skills [peer education intervention (PEI)] was compared
      with a time-equivalent attention control. Follow-up interviews were conducted at
      3 and 6 months post-baseline. PARTICIPANTS: Trial participants were HIV and
      hepatitis C virus (HCV) antibody-negative injection drug users aged 15-30 years.
      Participants who had at least one follow-up interview and reported injecting
      drugs in the previous 3 months at baseline were eligible for the present analysis
      (n = 690). MEASUREMENTS: At each interview, data were collected on the number of
      times participants injected drugs over the previous 3 months. FINDINGS: Twenty
      seven per cent of participants reported at least one 3-month period of injection
      cessation. In a multivariate, zero-inflated negative binomial regression
      adjusting for prior injection frequency, time of follow-up and psychosocial
      variables, PEI trial arm and smaller session size were associated significantly
      with injection cessation. Trial arm had no effect on the frequency of injection
      among those who continued to inject. CONCLUSIONS: HIV prevention interventions
      that encourage injection drug users to take on the role of peer educator may have
      the additional benefit of increasing the likelihood of injection cessation.
      Intervention group size is also an important consideration, with smaller groups
      having higher rates of cessation.

PMID- 21182556
TI  - Types of drinkers and drinking settings: an application of a mathematical model.
AB  - AIMS: US college drinking data and a simple population model of alcohol
      consumption are used to explore the impact of social and contextual parameters on
      the distribution of light, moderate and heavy drinkers. Light drinkers become
      moderate drinkers under social influence, moderate drinkers may change
      environments and become heavy drinkers. We estimate the drinking reproduction
      number, R(d) , the average number of individual transitions from light to
      moderate drinking that result from the introduction of a moderate drinker in a
      population of light drinkers. DESIGN AND SETTINGS: Ways of assessing and ranking
      progression of drinking risks and data-driven definitions of high- and low-risk
      drinking environments are introduced. Uncertainty and sensitivity analyses, via a
      novel statistical approach, are conducted to assess R(d) variability and to
      analyze the role of context on drinking dynamics. FINDINGS: Our estimates show
      R(d) well above the critical value of 1. R(d) estimates correlate positively with
      the proportion of time spent by moderate drinkers in high-risk drinking
      environments. R(d) is most sensitive to variations in local social mixing contact
      rates within low-risk environments. The parameterized model with college data
      suggests that high residence times of moderate drinkers in low-risk environments
      maintain heavy drinking. CONCLUSIONS: With regard to alcohol consumption in US
      college students, drinking places, the connectivity (traffic) between drinking
      venues and the strength of socialization in local environments are important
      determinants in transitions between light, moderate and heavy drinking as well as
      in long-term prediction of the drinking dynamics.

PMID- 21182557
TI  - Modelling the adverse effects associated with ecstasy use.
AB  - AIMS: Ecstasy, the street name for 3,4-meththylenedioxymethamphetamine, has been
      associated with a range of psychiatric symptoms and impaired psychological health
      in both problem and recreational users. The purpose of the present paper is to
      determine how these impairments are related to the history of polydrug use, and
      the conditions under which individuals ingest ecstasy. DESIGN: Associations
      between the variables of interest were investigated utilizing negative binomial
      regression. SETTING: Liverpool and Preston in the North West of England.
      PARTICIPANTS: A convenience sample of 159 recreational ecstasy/polydrug users (80
      males, 79 females). The sample was composed primarily of undergraduates.
      MEASUREMENTS: The dependent variable was the number of reported ecstasy-related
      adverse effects. Independent variables included quantitative aspects of ecstasy
      and other drug use, and the various beliefs and behaviours associated with
      ecstasy use. FINDINGS: The number of adverse effects was associated positively
      with life-time exposure to ecstasy and negatively with period of abstinence from
      the drug. Adverse effects were more common among those who consumed ecstasy and
      alcohol concurrently, but were unrelated to other aspects of polydrug use. They
      were unaffected by whether the user took precautions when using the drug, and
      only weakly related to prior beliefs concerning the effects of ecstasy.
      CONCLUSIONS: Greater life-time exposure to ecstasy and consuming the drug
      concurrently with alcohol increase the likelihood of experiencing adverse
      effects, including paranoia, poor general health, irritability, confusion and
      moodiness. Adverse effects decrease with the period of abstinence from the drug.

PMID- 21182558
TI  - Morphology, morphometrics, and molecular characterization of Bryophrya gemmea n.
      sp. (Ciliophora, Colpodea): implications for the phylogeny and evolutionary
      scenario for the formation of oral ciliature in the order Colpodida.
AB  - We studied the morphology, morphometry, resting, and reproductive cysts, as well
      as the molecular phylogeny of Bryophrya gemmea n. sp., a colpodid ciliate that
      was discovered in ephemeral puddles in Idaho, northwest United States. This new
      species is distinguished from congeners by the irregularly pentagonal adoral
      organelles, four to five vestibular kineties, the single micronucleus, and one to
      three rows of brightly refractive protuberant interkinetal cortical granules to
      the right of the preoral suture. Resting cysts have two distinct membranes and an
      outer mucous coat. As typical for most colpodids, reproduction occurs in division
      cysts but details of ontogenesis are unknown. The 18S rRNA gene sequence shows
      only weak support for the phylogenetic relationship between Bryophrya and the
      bryophryid genus Notoxoma previously inferred from morphologic characters.
      Further, our molecular phylogenies classify bryophryids rather basal within the
      order Colpodida, not supporting ordinal status suggested by morphologists. Based
      on molecular data and morphologic characters, the colpodid genus Ilsiella is
      removed from the family Marynidae and placed in a new family, Ilsiellidae.
      Considering the molecular data, an evolutionary scenario for the formation of
      colpodid oral structures from a cyrtolophosidid ancestor through a bryophryid
      intermediate is proposed.

PMID- 21182559
TI  - Another chloromyxid lineage: molecular phylogeny and redescription of Chloromyxum
      careni from the Asian horned frog Megophrys nasuta.
AB  - Infection with Chloromyxum careni Mutschmann, 1999 was found in the Asian horned
      frog Megophrys nasuta from Malaysia and Indonesia. Kidney was the only organ
      infected. Coelozoic plasmodia up to 300 MUm were localized in Bowman's space,
      embracing the glomerulus from all sides, or rarely in lumina of renal tubules.
      Plasmodia are polysporic, containing disporic pansporoblasts. Myxospores observed
      by light microscopy are colorless, variable in shape and size, measuring 6.0-8.5
      * 5.0-6.5 MUm, composed of two symmetrical valves joined by a meridian suture,
      containing four pyriform polar capsules 3.0-4.0 * 2.5-3.0 MUm and a single
      sporoplasm. Each valve possesses 14-24 (median 21) fine longitudinal ridges
      clearly visible only in scanning electron microscopy. Rarely, atypical spores
      with a markedly pointed posterior pole and only 6-10 surface ridges are present
      in plasmodia together with typical spores. Both small subunit (SSU) and large
      subunit (LSU) rRNA gene sequences possess extremely long GU-rich inserts. In all
      SSU and LSU rDNA-based phylogenetic analyses, C. careni clustered as a distinct
      basal branch to the Myxobolus+Myxidium lieberkuehni clade, out of the marine
      Chloromyxum clade containing Chloromyxum leydigi, the type species of the genus.
      These morphological and phylogenetic data suggest erection of a new genus for the
      C. careni lineage, but we conservatively treat it as a Chloromyxum sensu lato
      until more information is available.

PMID- 21182560
TI  - A new heterolobosean amoeba Solumitrus palustris n. g., n. sp. isolated from
      freshwater marsh soil.
AB  - During the course of research on the bacterial feeding behavior and resistance of
      amoebae to virulent pathogens, we isolated a new strain of amoeba from organic
      rich soil at the margin of freshwater swamp in the northeastern United States.
      Light microscopic morphology is characteristically heterolobosean, resembling
      vahlkampfiids, including a broadened, limax shape, and eruptive locomotion, but
      occasionally becoming more contracted and less elongated with lateral or anterior
      bulges and somewhat branching sparse, uroidal filaments. Electron microscopic
      evidence, including mitochondria with flattened cristae surrounded by rough
      endoplasmic reticulum, further indicates a heterolobosean affinity. The solitary
      nucleus contains a centrally located nucleolus. Cysts are rounded with
      occasionally an eccentrically located nucleus. The cyst walls are relatively
      thin, becoming crenated, and loosely enclosing the cyst when mature. Molecular
      genetic evidence places this isolate among the Heterolobosea, branching most
      closely in a clade including Allovahlkampfia spelaea and previously isolated, un
      named strains of soil amoebae. Based on differentiated features, including
      morphology of the uroid, cyst wall structure, and molecular genetic evidence that
      distinguish it from A. spelaea, a new genus and species, Solumitrus palustris, is
      proposed for this new heterolobosean.

PMID- 21182561
TI  - Patterns of 5' untranslated region length distribution in Encephalitozoon
      cuniculi: implications for gene regulation and potential links between
      transcription and splicing.
AB  - Encephalitozoon cuniculi, a eukaryotic intracellular parasite belonging to the
      group Microsporidia, has a highly reduced and compacted genome. Its mRNA
      transcripts have been found to differ between the two life stages, the spore and
      meront, of the parasite. Spore transcripts generally have more transcription
      start sites, longer 5' untranslated regions (UTRs), and overlap more frequently
      with upstream genes than those of meronts. A previous analysis of 31 meront gene
      transcripts showed that most have short 5'UTRs, and intron-containing genes,
      mostly ribosomal protein genes, exclusively have very short 5'UTRs. Here we
      analyzed a larger set of transcripts from meronts, and we find a pattern of 5'UTR
      length distribution similar to other reduced genomes. There is an abundance of
      very short 5'UTRs that are <20 bp in length, and very few 5'UTRs that are much
      longer. We also find a relationship between gene categories and 5'UTR length:
      intron-containing genes and ribosomal protein genes have exclusively short
      5'UTRs. We suggest that the abundance of short 5'UTRs may be related to a class
      of highly expressed genes that benefit the parasite's growth cycle. Also, the
      longer 5'UTRs may be playing a role in down-regulating expression of genes that
      require temporal or environment-induced expression.

PMID- 21182562
TI  - Evidence for a previously unrecognized mycobacterial endosymbiont in Acanthamoeba
      castellanii strain Ma (ATCC (r) 50370 TM).
AB  - We describe the isolation of a mycobacterium from Acanthamoeba castellanii strain
      Ma (ATCC((r)) 50370(TM)). The mycobacterium resides within vacuoles of A.
      castellanii, can be cultured by routine methodologies, and is a member of the
      Mycobacterium avium complex. Previously unrecognized mycobacterial endosymbionts
      are likely common among strains of Acanthamoeba housed at culture collections.

PMID- 21182563
TI  - In memoriam: Jiri Lom (1931-2010)-protozoology with love.

PMID- 21182564
TI  - Comparison of succinylcholine and rocuronium for first-attempt intubation success
      in the emergency department.
AB  - OBJECTIVES: The objective was to determine the effect of paralytic type and dose
      on first-attempt rapid sequence intubation (RSI) success in the emergency
      department (ED). METHODS: This was a retrospective evaluation of information
      collected prospectively in a quality improvement database between July 1, 2007,
      and October 31, 2008. Information regarding all intubations performed in a
      tertiary care ED was recorded in this database. All RSI performed using
      succinylcholine or rocuronium were included. Logistic regression was used to
      analyze the effect of paralytic type and dosing, as well as age, sex, body mass
      index, physician experience, device type, and presence of difficult airway
      predictors on first attempt RSI success. RESULTS: A total of 327 RSI were
      included in the final analyses. All patients received etomidate as the induction
      sedative and were successfully intubated. Of these, 113 and 214 intubations were
      performed using succinylcholine and rocuronium, respectively. The rate of first
      attempt intubation success was similar between the succinylcholine and rocuronium
      groups (72.6% vs. 72.9%, p=0.95). Median doses used for succinylcholine and
      rocuronium were 1.65 mg/kg (interquartile range [IQR]=1.26-1.95 mg/kg) and 1.19
      mg/kg (IQR=1-1.45 mg/kg), respectively. In the univariate logistic regression
      analyses, variables predictive of first-attempt intubation success were laryngeal
      view (more success if Grade 1 or 2 compared to Grade 3 or 4 of the Cormack-Lehane
      classification, odds ratio [OR] =55.18, 95% confidence interval [CI]=18.87 to
      161.39), intubation device (less success if direct laryngoscopy, OR=0.57, 95%
      CI=0.34 to 0.96), and presence of a difficult airway predictor (OR=0.55, 95%
      CI=0.31 to 0.99). In the multivariate analysis, the only variable predictive of
      first-attempt intubation success was laryngeal view. CONCLUSIONS: Succinylcholine
      and rocuronium are equivalent with regard to first-attempt intubation success in
      the ED when dosed according to the ranges used in this study.

PMID- 21182565
TI  - Relationship between cocaine use and coronary artery disease in patients with
      symptoms consistent with an acute coronary syndrome.
AB  - OBJECTIVES: Observational studies of patients with cocaine-associated myocardial
      infarction have suggested more coronary disease than expected on the basis of
      patient age. The study objective was to determine whether cocaine use is
      associated with coronary disease in low- to intermediate-risk emergency
      department (ED) patients with potential acute coronary syndrome (ACS). METHODS:
      The authors conducted a cross-sectional study of low- to intermediate-risk
      patients<60 years of age who received coronary computerized tomographic
      angiography (CTA) for evaluation of coronary artery disease (CAD) in the ED.
      Patients were classified into three groups with respect to CAD: maximal stenosis
      <25%, 25% to 49%, and >=50%. Prespecified multivariate modeling (generalized
      estimating equations) was used to assess relationship between cocaine and CAD.
      RESULTS: Of 912 enrolled patients, 157 (17%) used cocaine. A total of 231
      patients had CAD >=25%; 111 had CAD >=50%. In univariate analysis, cocaine use
      was not associated with a lesion 25% or greater (12% vs. 14%; relative risk
      [RR]=0.89, 95% confidence interval [CI]=0.5 to 1.4) or 50% or greater (12% vs.
      11%; RR=1.15, 95% CI=0.6 to 2.3). In multivariate modeling adjusting for age,
      race, sex, cardiac risk factors, and Thrombosis in Myocardial Infarction (TIMI)
      score, cocaine use was not associated with the presence of any coronary lesion
      (adjusted RR=0.95, 95% CI=0.69 to 1.31) or coronary lesions 50% or greater
      (adjusted RR=0.78, 95% CI=0.45 to 1.38). There was also no relationship between
      repetitive cocaine use and coronary calcifications or between recent cocaine use
      and CAD. CONCLUSIONS: In symptomatic ED patients at low to intermediate risk of
      an ACS, cocaine use was not associated with an increased likelihood of coronary
      disease after adjustment for age, race, sex, and other risk factors for coronary
      disease.

PMID- 21182566
TI  - The treatment of pediatric gastroenteritis: a comparative analysis of pediatric
      emergency physicians' practice patterns.
AB  - OBJECTIVES: Acute gastroenteritis is a very common emergency department (ED)
      diagnosis accounting for greater than 1.5 million outpatient visits and 200,000
      hospitalizations annually among children in the United States. Although
      guidelines exist to assist clinicians, they do not clearly address topics for
      which evidence is new or limited, including the use of antiemetic agents,
      probiotics, and intravenous (IV) fluid rehydration regimens. This study sought to
      describe the ED treatments administered to children with acute gastroenteritis
      and to compare management between Canadian and U.S. physicians practicing
      pediatric emergency medicine (PEM). METHODS: Members of PEM research networks
      located in Canada and the United States were invited to participate in a cross
      sectional, Internet-based survey. Participants were included if they are
      attending physicians and provide care to patients <18 years of age in an ED.
      RESULTS: In total, 235 of 339 (73%) eligible individuals responded. A total of
      103 of 136 Canadian physicians (76%) report initiating oral rehydration therapy
      (ORT) in children with moderate dehydration, compared with 44 of 94 (47%) of
      their U.S. colleagues (p<0.001). The latter more often administer antiemetic
      agents to children with vomiting (67% vs. 45%; p=0.001). American physicians
      administer larger IV fluid bolus volumes (p<0.001) and over shorter time periods
      (p=0.001) and repeat the fluid boluses more frequently (p<0.001). Probiotics are
      routinely recommended by only 35 of 230 respondents (15%). CONCLUSIONS: The
      treatment of pediatric gastroenteritis varies by geographic location and differs
      significantly between Canadian and American PEM physicians. Oral rehydration
      continues to be underused, particularly in the United States. Probiotic use
      remains uncommon, while ondansetron administration has become routine. Children
      frequently receive IV rehydration, with the rate and volume administered being
      greater in the United States.

PMID- 21182567
TI  - International emergency medicine: a review of the literature from 2009.
AB  - As the specialty of emergency medicine evolves in countries around the world, and
      as interest in international emergency medicine (IEM) grows within the United
      States, the IEM Literature Review Group recognizes an ongoing need for a high
      quality, consolidated, and easily accessible evidence base of literature. The IEM
      Literature Review Group produces an annual publication that strives to provide
      readers with access to the highest quality and most relevant IEM research from
      the previous year. This publication represents our fifth annual review, covering
      the top 24 IEM research articles published in 2009. Articles were selected for
      the review according to explicit, predetermined criteria that emphasize both
      methodologic quality and impact of the research. It is our hope that this annual
      review acts as a forum for disseminating best practices, while also stimulating
      further research in the field of IEM.

PMID- 21182569
TI  - Neuroadaptation of GABAergic transmission in the central amygdala during chronic
      morphine treatment.
AB  - We investigated possible alterations of pharmacologically-isolated, evoked
      GABA(A) inhibitory postsynaptic potentials (eIPSPs) and miniature GABA(A)
      inhibitory postsynaptic currents (mIPSCs) in the rat central amygdala (CeA)
      elicited by acute application of u-opioid receptor (MOR) agonists (DAMGO and
      morphine; 1 uM) and by chronic morphine treatment with morphine pellets. The
      acute activation of MORs decreased the amplitudes of eIPSPs, increased paired
      pulse facilitation (PPF) of eIPSPs and decreased the frequency (but not the
      amplitude) of mIPSCs in a majority of CeA neurons, suggesting that acute MOR
      dependent modulation of this GABAergic transmission is mediated predominantly via
      presynaptic inhibition of GABA release. We observed no significant changes in the
      membrane properties, eIPSPs, PPF or mIPSCs of CeA neurons during chronic morphine
      treatment compared to CeA of naive or sham rats. Superfusion of the MOR
      antagonist CTOP (1 uM) increased the mean amplitude of eIPSPs in a majority of
      CeA neurons to the same degree in both naive/sham and morphine-treated rats,
      suggesting a tonic activation of MORs in both conditions. Superfusion of DAMGO
      decreased eIPSP amplitudes and the frequency of mIPSCs equally in both naive/sham
      and morphine-treated rats but decreased the amplitude of mIPSCs only in morphine
      treated rats, an apparent postsynaptic action. Our combined findings suggest the
      development of tolerance of the CeA GABAergic system to inhibitory effects of
      acute activation of MORs on presynaptic GABA release and possible alteration of
      MOR-dependent postsynaptic mechanisms that may represent important
      neuroadaptations of the GABAergic and MOR systems during chronic morphine
      treatment.

PMID- 21182570
TI  - Effect of methamphetamine dependence on heart rate variability.
AB  - Methamphetamine (METH) is an increasing popular and highly addictive stimulant
      associated with autonomic nervous system (ANS) dysfunction, cardiovascular
      pathology and neurotoxicity. Heart rate variability (HRV) has been used to assess
      autonomic function and predict mortality in cardiac disorders and drug
      intoxication, but has not been characterized in METH use. We recorded HRV in a
      sample of currently abstinent individuals with a history of METH dependence
      compared to age- and gender-matched drug-free comparison subjects. HRV was
      assessed using time domain, frequency domain, and non-linear entropic analyses in
      17 previously METH-dependent and 21 drug-free comparison individuals during a 5
      minute rest period. The METH-dependent group demonstrated significant reduction
      in HRV, reduced parasympathetic activity, and diminished heartbeat complexity
      relative to comparison participants. More recent METH use was associated with
      increased sympathetic tone. Chronic METH exposure may be associated with
      decreased HRV, impaired vagal function, and reduction in heart rate complexity as
      assessed by multiple methods of analysis. We discuss and review evidence that
      impaired HRV may be related to the cardiotoxic or neurotoxic effects of prolonged
      METH use.

PMID- 21182571
TI  - The endocannabinoid system modulates the valence of the emotion associated to
      food ingestion.
AB  - Endocannabinoids (eCBs) are mediators of the homeostatic and hedonic systems that
      modulate food ingestion. Hence, eCBs, by regulating the hedonic system, may be
      modulating the valence of the emotion associated to food ingestion (positive:
      pleasant or negative: unpleasant). Our first goal was to demonstrate that
      palatable food induces conditioned place preference (CPP), hence a positive
      valence emotion. Additionally, we analyzed if this CPP is blocked by AM251,
      inducing a negative valence emotion, meaning avoiding the otherwise pursued
      compartment. The second goal was to demonstrate that CPP induced by regular food
      would be strengthened by the simultaneous administration of anandamide or
      oleamide, and if such, CPP is blocked by AM251. Finally, we tested the capacity
      of eCBs (without food) to induce CPP. Our results indicate that rats readily
      developed CPP to palatable food, which was blocked by AM251. The CPP induced by
      regular food was strengthened by eCBs and blocked by AM251. Finally, oleamide,
      unlike anandamide, induced CPP. These results showed that eCBs mediate the
      positive valence (CPP) of the emotion associated to food ingestion. It was also
      observed that the blockade of the CB1 receptor causes a loss of correlation
      between food and CPP (negative valence: avoidance). These data further support
      the role of eCBs as regulators of the hedonic value of food.

PMID- 21182572
TI  - Repeated exposure to moderate doses of ethanol augments hippocampal glutamate
      neurotransmission by increasing release.
AB  - The present study used conventional and quantitative microdialysis to assess
      glutamatergic and GABAergic neurotransmission in the hippocampal CA3 area of the
      rat following a moderate-dose ethanol treatment regimen. Male Wistar rats
      received 3.4 g/kg of ethanol or water for 6 days via gastric gavage.
      Microdialysis experiments commenced 2 days later. Basal and depolarization
      induced glutamate overflow were significantly elevated in ethanol-treated
      animals. Basal and depolarization-induced gamma-aminobutyric acid (GABA) overflow
      were unaltered. Quantitative no-net-flux microdialysis was used to determine if
      changes in dialysate glutamate levels following ethanol administration are due to
      an increase in release or a decrease in uptake. To confirm the validity of this
      method for quantifying basal glutamate dynamics, extracellular concentrations of
      glutamate and the extraction fraction, which reflects changes in analyte
      clearance, were quantified in response to retro-dialysis of the glutamate uptake
      blocker trans-pyrrolidine-2,4-dicarboxylic acid (tPDC). tPDC significantly
      decreased the extraction fraction for glutamate, resulting in augmented
      extracellular glutamate concentrations. Repeated ethanol administration did not
      alter the glutamate extraction fraction. However, extracellular glutamate
      concentrations were significantly elevated, indicating that glutamate release is
      increased as a consequence of repeated ethanol administration. These data
      demonstrate that repeated bouts of moderate ethanol consumption alter basal
      glutamate dynamics in the CA3 region of the dorsal hippocampus. Basal glutamate
      release is augmented, whereas glutamate uptake is unchanged. Furthermore, they
      suggest that dysregulation of glutamate transmission in this region may
      contribute to the previously documented deficits in cognitive function associated
      with moderate dose ethanol use.

PMID- 21182573
TI  - Brain reactivity to emotional, neutral and cigarette-related stimuli in smokers.
AB  - Addiction has been described as the pathological usurpation of the neural
      mechanisms normally involved in emotional processing. Event-related potentials
      (ERPs) can provide a non-invasive index of neural responses associated with the
      processing of emotionally relevant stimuli and serve as a tool for examining
      temporal and spatial commonalities between the processing of intrinsically
      motivating stimuli and drug cues. Before beginning a smoking cessation program,
      116 smokers participated in a laboratory session in which dense-array ERPs (129
      sensors) were recorded during the presentation of pictures with emotional
      (pleasant and unpleasant), neutral and cigarette-related content. ERP differences
      among categories were analyzed with use of randomization tests on time regions of
      interest identified by temporal principal component analysis. Both emotional and
      cigarette-related pictures prompted significantly more positivity than did
      neutral pictures over central, parietal, and frontal sites in the 452-508 ms time
      window. During the 212-316 ms time window, both pleasant and cigarette-related
      pictures prompted less positivity than neutral images did. Cigarette-related
      pictures enhanced the amplitude of the P1 component (136-144 ms) above the levels
      measured in the emotional and neutral conditions. These results support the
      hypothesis that for smokers, cigarette-related cues are motivationally relevant
      stimuli that capture attentional resources early during visual processing and
      engage brain circuits normally involved in the processing of intrinsically
      emotional stimuli.

PMID- 21182576
TI  - Gene cluster for biosynthesis of thermophilin 1277--a lantibiotic produced by
      Streptococcus thermophilus SBT1277, and heterologous expression of TepI, a novel
      immunity peptide.
AB  - AIMS: To identify genes cluster for thermophilin 1277 produced by Streptococcus
      thermophilus SBT1277. METHODS AND RESULTS: To identify genes for thermophilin
      1277 production, the chromosomal DNA region surrounding the structural gene,
      tepA, was sequenced using a primer-walking method. The thermophilin 1277
      biosynthesis gene locus (tep) is a 9.9-kb region, which consists of at least ten
      open reading frames (ORFs) in the following order: tepAMTFEGKRI and ORF4.
      Homology analysis showed high similarity to genes involved in bovicin HJ50
      production by Streptococcus bovis HJ50. tepI encodes a novel, small, positively
      charged hydrophobic peptide of 52 amino acids, which contains a putative
      transmembrane segment. By heterologous expression in Lactococcus lactis ssp.
      cremoris MG1363, the TepI-expressing strain exhibited at least 1.3 times higher
      resistance to thermophilin 1277. CONCLUSIONS: Thermophilin 1277 biosynthesis
      genes were encoded by a 9.9-kbp region containing at least ten ORFs. TepI is a
      novel immunity peptide, which protected Strep. thermophilus SBT1277 against
      thermophilin 1277 in addition to TepFEG, a putative ABC transporter. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This is the first report regarding a lantibiotic gene
      cluster produced by Strep. thermophilus strain.

PMID- 21182574
TI  - The role of amygdaloid brain-derived neurotrophic factor, activity-regulated
      cytoskeleton-associated protein and dendritic spines in anxiety and alcoholism.
AB  - Innate anxiety appears to be a robust factor in the promotion of alcohol intake,
      possibly due to the anxiolytic effects of self-medication with alcohol. Brain
      derived neurotrophic factor (BDNF) and its downstream target, activity-regulated
      cytoskeleton-associated (Arc) protein, play a role in the regulation of synaptic
      function and structure. In order to examine the role of the BDNF-Arc system and
      associated dendritic spines in the anxiolytic effects of ethanol, we investigated
      the effects of acute ethanol exposure on anxiety-like behaviors of alcohol
      preferring (P) and -nonpreferring (NP) rats. We also examined changes in the
      expression of BDNF and Arc, and dendritic spine density (DSD), in amygdaloid
      brain regions of P and NP rats with or without ethanol exposure. It was found
      that in comparison with NP rats, P rats displayed innate anxiety-like behaviors,
      and had lower mRNA and protein levels of both BDNF and Arc, and also had lower
      DSD in the central amygdala (CeA) and medial amygdala (MeA), but not in the
      basolateral amygdala (BLA). Acute ethanol treatment had an anxiolytic effect in
      P, but not in NP rats, and was associated with an increase in mRNA and protein
      levels of BDNF and Arc, and in DSD in the CeA and MeA, but not BLA. These results
      suggest that innate deficits in BDNF-Arc levels, and DSD, in the CeA and MeA may
      be involved in the anxiety-like and excessive alcohol-drinking behaviors of P
      rats, as ethanol increased these amygdaloid synaptic markers and produced
      anxiolytic effects in P rats, but not NP rats.

PMID- 21182575
TI  - Endogenous GDNF in ventral tegmental area and nucleus accumbens does not play a
      role in the incubation of heroin craving.
AB  - Glial cell line-derived neurotrophic factor (GDNF) activity in ventral tegmental
      area (VTA) mediates the time-dependent increases in cue-induced cocaine-seeking
      after withdrawal (incubation of cocaine craving). Here, we studied the generality
      of these findings to incubation of heroin craving. Rats were trained to self
      administer heroin for 10 days (6 hours/day; 0.075 mg/kg/infusion; infusions were
      paired with a tone-light cue) and tested for cue-induced heroin-seeking in
      extinction tests after 1, 11 or 30 withdrawal days. Cue-induced heroin seeking
      was higher after 11 or 30 days than after 1 day (incubation of heroin craving),
      and the time-dependent increases in extinction responding were associated with
      time-dependent changes in GDNF mRNA expression in VTA and nucleus accumbens.
      Additionally, acute accumbens (but not VTA) GDNF injections (12.5 ug/side)
      administered 1-3 hours after the last heroin self-administration training session
      enhanced the time-dependent increases in extinction responding after withdrawal.
      However, the time-dependent increases in extinction responding after withdrawal
      were not associated with changes in GDNF protein expression in VTA and accumbens.
      Additionally, interfering with endogenous GDNF function by chronic delivery of
      anti-GDNF monoclonal neutralizing antibodies (600 ng/side/day) into VTA or
      accumbens had no effect on the time-dependent increases in extinction responding.
      In summary, heroin self-administration and withdrawal regulate VTA and accumbens
      GDNF mRNA expression in a time-dependent manner, and exogenous GDNF
      administration into accumbens but not VTA potentiates cue-induced heroin seeking.
      However, based on the GDNF protein expression and the anti-GDNF monoclonal
      neutralizing antibodies manipulation data, we conclude that neither accumbens nor
      VTA endogenous GDNF mediates the incubation of heroin craving.

PMID- 21182577
TI  - The challenge to quantify Listeria monocytogenes--a model leading to new aspects
      in molecular biological food pathogen detection.
AB  - In this work, we discuss the latest insights concerning advantages and
      disadvantages and the nature of microbiological and molecular methods for
      quantitative food pathogen detection. The assessment of molecular methods must be
      brought on a basis that considers the nature of molecular methods and their
      underlying mechanism. A potential approach to setting up the development,
      validation and structure of an analytical chain is presented based on
      quantitative real-time PCR (qPCR). This is analysed exemplary on the basis of
      recent work using the model organism Listeria monocytogenes. Several
      prerequisites for successful quantitative detection of this pathogen will be
      discussed. In particular, sample preparation, controls for all methodical steps
      and the validation of the core assay qPCR are addressed, which constitute the
      basis for a reliable analytical detection chain for molecular biological pathogen
      detection from food. Microbiological methods are analysed based on growth of the
      single cell, which is the fundament of these traditional methods.

PMID- 21182578
TI  - Mechanisms and effects of retention of over-expressed aquaporin AtPIP2;1 in the
      endoplasmic reticulum.
AB  - Plasma membrane intrinsic proteins (PIPs) are aquaporins that mediate water
      transport across the plant plasma membrane (PM). The present work addresses,
      using Arabidopsis AtPIP2;1 as a model, the mechanisms and significance of
      trafficking of newly synthesized PIPs from the endoplasmic reticulum (ER) to the
      Golgi apparatus. A functional diacidic export motif (Asp4-Val5-Glu6) was
      identified in the N-terminal tail of AtPIP2;1, using expression in transgenic
      Arabidopsis of site-directed mutants tagged with the green fluorescent protein
      (GFP). Confocal fluorescence imaging and a novel fluorescence recovery after
      photobleaching application based on the distinct diffusion of PM and
      intracellular AtPIP2;1-GFP forms revealed a retention in the ER of diacidic
      mutated forms, but with quantitative differences. Thus, the individual role of
      the two acidic Asp4 and Glu6 residues was established. In addition, expression in
      transgenic Arabidopsis of ER-retained AtPIP2;1-GFP constructs reduced the root
      hydraulic conductivity. Co-expression of AtPIP2;1-GFP and AtPIP1;4-mCherry
      constructs suggested that ER-retained AtPIP2;1-GFP may interact with other PIPs
      to hamper their trafficking to the PM, thereby contributing to inhibition of root
      cell hydraulic conductivity.

PMID- 21182580
TI  - Conversion of a failed pouch to a continent ileostomy: a controversy.

PMID- 21182581
TI  - Commentary: The persisting presacral sinus following anastomotic leakage after
      anterior resection: incidence and outcome.

PMID- 21182586
TI  - Donor antioxidant strategy prolongs cardiac allograft survival by attenuating
      tissue dendritic cell immunogenicity(?).
AB  - Ischemic reperfusion injury (IRI) enhances allograft immunogenicity, worsens
      transplantation outcome, and is the primary cause of activation of the recipient
      innate immune response, resulting in subsequent amplification of the alloimmune
      adaptive response. Here, we aimed at demonstrating that the link between innate
      injury and alloimmunity occurs predominantly through activation of allograft
      derived dendritic cells (ADDC). Perfusion of MCI-186, a free radical scavenger,
      into donor cardiac allografts prior to transplantation resulted in prolongation
      of complete MHC-mismatched allograft survival in the absence of immunosuppression
      (MST of 8 vs. 26 days). This prolongation was associated with a reduction in
      trafficking of ADDC to recipient lymphoid tissue as well as a reduction in T cell
      priming. Depleting ADDC with diphtheria toxin (using DTR-GFP-DC mice as donors)
      24 h prior to transplant resulted in abrogation of the prolongation observed with
      MCI-186 treatment, demonstrating that the beneficial effect of MCI-186 is
      mediated by ADDC. This donor-specific anti-ischemic regimen was also shown to
      reduce chronic rejection, which represents the primary obstacle to long-term
      allograft acceptance. These data for the first time establish a basis for donor
      anti-ischemic strategies, which in the ever-expanding marginal donor pools, can
      be instituted to promote engraftment.

PMID- 21182587
TI  - Bcl-2 and Bcl-xL play important roles in the crosstalk between autophagy and
      apoptosis.
AB  - Autophagy and apoptosis play important roles in the development, cellular
      homeostasis and, especially, oncogenesis of mammals. They may be triggered by
      common upstream signals, resulting in combined autophagy and apoptosis. In other
      instances, they may be mutually exclusive. Recent studies have suggested possible
      molecular mechanisms for crosstalk between autophagy and apoptosis. Bcl-2 and Bcl
      xL, the well-characterized apoptosis guards, appear to be important factors in
      autophagy, inhibiting Beclin 1-mediated autophagy by binding to Beclin 1. In
      addition, Beclin 1, Bcl-2 and Bcl-xL can cooperate with Atg5 or Ca(2+) to
      regulate both autophagy and apoptosis. Thus, Bcl-2 and Bcl-xL represent a
      molecular link between autophagy and apoptosis. Here, we discuss the possible
      roles of Bcl-2 and Bcl-xL in apoptosis and autophagy, and the crosstalk between
      them.

PMID- 21182588
TI  - On the reaction of D-amino acid oxidase with dioxygen: O2 diffusion pathways and
      enhancement of reactivity.
AB  - Evidence is accumulating that oxygen access in proteins is guided and controlled.
      We also have recently described channels that might allow access of oxygen to
      pockets at the active site of the flavoprotein D-amino acid oxidase (DAAO) that
      have a high affinity for dioxygen and are in close proximity to the flavin. With
      the goal of enhancing the reactivity of DAAO with oxygen, we have performed site
      saturation mutagenesis at three positions that flank the putative oxygen channels
      and high-affinity sites. The most interesting variants at positions 50, 201 and
      225 were identified by a screening procedure at low oxygen concentration. The
      biochemical properties of these variants have been studied and compared with
      those of wild-type DAAO, with emphasis on the reactivity of the reduced enzyme
      species with dioxygen. The substitutions at positions 50 and 225 do not enhance
      this reaction, but mainly affect the protein conformation and stability. However,
      the T201L variant shows an up to a threefold increase in the rate constant for
      reaction of O(2) with reduced flavin, together with a fivefold decrease in the
      K(m) for dioxygen. This effect was not observed when a valine is located at
      position 201, and is thus attributed to a specific alteration in the micro
      environment of one high-affinity site for dioxygen (site B) close to the flavin
      that plays an important role in the storage of oxygen. The increase in O(2)
      reactivity observed for T201L DAAO is of great interest for designing new
      flavoenzymes for biotechnological applications.

PMID- 21182589
TI  - P25alpha / TPPP expression increases plasma membrane presentation of the dopamine
      transporter and enhances cellular sensitivity to dopamine toxicity.
AB  - Parkinson's disease is characterized by preferential degeneration of the dopamine
      producing neurons of the brain stem substantia nigra. Imbalances between
      mechanisms governing dopamine transport across the plasma membrane and cellular
      storage vesicles increase the level of toxic pro-oxidative cytosolic dopamine.
      The microtubule-stabilizing protein p25alpha accumulates in dopaminergic neurons
      in Parkinson's disease. We hypothesized that p25alpha modulates the subcellular
      localization of the dopamine transporter via effects on sorting vesicles, and
      thereby indirectly affects its cellular activity. Here we show that co-expression
      of the dopamine transporter with p25alpha in HEK-293-MSR cells increases dopamine
      uptake via increased plasma membrane presentation of the transporter. No direct
      interaction between p25alpha and the dopamine transporter was demonstrated, but
      they co-fractionated during subcellular fractionation of brain tissue from
      striatum, and direct binding of p25alpha peptides to brain vesicles was
      demonstrated. Truncations of the p25alpha peptide revealed that the requirement
      for stimulating dopamine uptake is located in the central core and were similar
      to those required for vesicle binding. Co-expression of p25alpha and the dopamine
      transporter in HEK-293-MSR cells sensitized them to the toxicity of extracellular
      dopamine. Neuronal expression of p25alpha thus holds the potential to sensitize
      the cells toward dopamine and toxins carried by the dopamine transporter.

PMID- 21182590
TI  - Interruption of triacylglycerol synthesis in the endoplasmic reticulum is the
      initiating event for saturated fatty acid-induced lipotoxicity in liver cells.
AB  - The aim of the present study was to investigate in detail the molecular
      mechanisms by which free fatty acids induce liver toxicity in liver cells. HepG2
      and Huh7 human liver cell lines were exposed to varying concentrations of
      stearate (18:0), oleate (18:1), or mixtures of the two fatty acids, and the
      effects on cell proliferation, lipid droplet accumulation and induction of
      endoplasmic reticulum stress and apoptosis were evaluated. It was observed that:
      (a) stearate, but not oleate, inhibited cell proliferation and induced cell
      death; (b) stearate-induced cell death had the characteristics of endoplasmic
      reticulum stress-mediated and mitochondrial-mediated apoptosis; (c) the
      activation of stearate in the form of stearoyl-CoA was a necessary step for the
      lipotoxic effect; (d) the capacity of cells to produce and accumulate
      triacylglycerols in the form of lipid droplets was interrupted following exposure
      to stearate, whereas it proceeded normally in oleate-treated cells; and (e) the
      presence of relatively low amounts of oleate protected cells from stearate
      induced toxicity and restored the ability of the cells to accumulate
      triacylglycerols. Our data suggest that interruption of triacylglycerol synthesis
      in the endoplasmic reticulum, apparently because of the formation of a pool of
      oversaturated intermediates, represents the key initiating event in the mechanism
      of saturated fatty acid-induced lipotoxicity.

PMID- 21182592
TI  - Membrane targeting and pore formation by the type III secretion system
      translocon.
AB  - The type III secretion system (T3SS) is a complex macromolecular machinery
      employed by a number of Gram-negative species to initiate infection. Toxins
      secreted through the system are synthesized in the bacterial cytoplasm and
      utilize the T3SS to pass through both bacterial membranes and the periplasm, thus
      being introduced directly into the eukaryotic cytoplasm. A key element of the
      T3SS of all bacterial pathogens is the translocon, which comprises a pore that is
      inserted into the membrane of the target cell, allowing toxin injection. Three
      macromolecular partners associate to form the translocon: two are hydrophobic and
      one is hydrophilic, and the latter also associates with the T3SS needle. In this
      review, we discuss recent advances on the biochemical and structural
      characterization of the proteins involved in translocon formation, as well as
      their participation in the modification of intracellular signalling pathways upon
      infection. Models of translocon assembly and regulation are also discussed.

PMID- 21182591
TI  - Kinetics of dextran-independent alpha-(1->3)-glucan synthesis by Streptococcus
      sobrinus glucosyltransferase I.
AB  - Glucosyltransferase (GTF)-I from cariogenic Streptococcus sobrinus elongates the
      alpha-(1->3)-linked glucose polymer branches on the primer dextran bound to the C
      terminal glucan-binding domain. We investigated the GTF-I-catalyzed glucan
      synthesis reaction in the absence of the primer dextran. The time course of
      saccharide production during dextran-independent glucan synthesis from sucrose
      was analyzed. Fructose and glucose were first produced by the sucrose hydrolysis.
      Leucrose was subsequently produced, followed by insoluble glucan [alpha-(1->3)
      linked glucose polymers] after a lag phase. High levels of intermediate
      nigerooligosaccharide series accumulation were characteristically not observed
      during the lag phase. The results from the enzymatic activity of the acceptor
      reaction for the nigerooligosaccharide with a degree of polymerization of 2-6 and
      methyl alpha-D-glucopyranoside as a glucose analog indicate that the activity
      increased with an increase in the degree of polymerization. The production of
      insoluble glucan was numerically simulated using the fourth-order Runge-Kutta
      method with the kinetic parameters estimated from the enzyme assay. The simulated
      time course provided a profile similar to that of experimental data. These
      results define the relationship between the kinetic properties of GTF-I and the
      time course of saccharide production. These results are discussed with respect to
      a mechanism that underlies efficient glucan synthesis.

PMID- 21182593
TI  - Abstracts of the 10th Biennial Meeting of the Asia-Pacific Society of
      Neurochemistry. October 18-20, 2010. Phuket, Thailand.

PMID- 21182594
TI  - Regulation of DNA fragmentation: the role of caspases and phosphorylation.
AB  - DNA fragmentation is a hallmark of apoptosis that is induced by apoptotic stimuli
      in various cell types. Apoptotic signal pathways, which eventually cause DNA
      fragmentation, are largely mediated by the family of cysteinyl aspartate-specific
      protease caspases. Caspases mediate apoptotic signal transduction by cleavage of
      apoptosis-implicated proteins and the caspases themselves. In the process of
      caspase activation, reversible protein phosphorylation plays an important role.
      The activation of various proteins is regulated by phosphorylation and
      dephosphorylation, both upstream and downstream of caspase activation. Many
      kinases/phosphatases are involved in the control of cell survival and death,
      including the mitogen-activated protein kinase signal transduction pathways.
      Reversible protein phosphorylation is involved in the widespread regulation of
      cellular signal transduction and apoptotic processes. Therefore,
      phosphatase/kinase inhibitors are commonly used as apoptosis inducers/inhibitors.
      Whether protein phosphorylation induces apoptosis depends on many factors, such
      as the type of phosphorylated protein, the degree of activation and the influence
      of other proteins. Phosphorylation signaling pathways are intricately
      interrelated; it was previously shown that either induction or inhibition of
      phosphorylation causes cell death. Determination of the relationship between
      protein and phosphorylation helps to reveal how apoptosis is regulated. Here we
      discuss DNA fragmentation and protein phosphorylation, focusing on caspase and
      serine/threonine protein phosphatase activation.

PMID- 21182595
TI  - Crystal structure of the cambialistic superoxide dismutase from Aeropyrum pernix
      K1--insights into the enzyme mechanism and stability.
AB  - Aeropyrum pernix K1, an aerobic hyperthermophilic archaeon, produces a
      cambialistic superoxide dismutase that is active in the presence of either of Mn
      or Fe. The crystal structures of the superoxide dismutase from A. pernix in the
      apo, Mn-bound and Fe-bound forms were determined at resolutions of 1.56, 1.35 and
      1.48 A, respectively. The overall structure consisted of a compact homotetramer.
      Analytical ultracentrifugation was used to confirm the tetrameric association in
      solution. In the Mn-bound form, the metal was in trigonal bipyramidal
      coordination with five ligands: four side chain atoms and a water oxygen. One
      aspartate and two histidine side chains ligated to the central metal on the
      equatorial plane. In the Fe-bound form, an additional water molecule was observed
      between the two histidines on the equatorial plane and the metal was in
      octahedral coordination with six ligands. The additional water occupied the
      postulated superoxide binding site. The thermal stability of the enzyme was
      compared with superoxide dismutase from Thermus thermophilus, a thermophilic
      bacterium, which contained fewer ion pairs. In aqueous solution, the stabilities
      of the two enzymes were almost identical but, when the solution contained
      ethylene glycol or ethanol, the A. pernix enzyme had significantly higher thermal
      stability than the enzyme from T. thermophilus. This suggests that dominant ion
      pairs make A. pernix superoxide dismutase tolerant to organic media.

PMID- 21182596
TI  - Angiopoietin-like proteins: emerging targets for treatment of obesity and related
      metabolic diseases.
AB  - Obesity and related metabolic diseases, such as type 2 diabetes, hypertension and
      hyperlipidemia are an increasingly prevalent medical and social problem in
      developed and developing countries. These conditions are associated with
      increased risk of cardiovascular disease, the leading cause of death. Therefore,
      it is important to understand the molecular basis underlying obesity and related
      metabolic diseases in order to develop effective preventive and therapeutic
      approaches against these conditions. Recently, a family of proteins structurally
      similar to the angiogenic-regulating factors known as angiopoietins was
      identified and designated 'angiopoietin-like proteins' (ANGPTLs). Encoded by
      seven genes, ANGPTL1-7 all possess an N-terminal coiled-coil domain and a C
      terminal fibrinogen-like domain, both characteristic of angiopoietins. ANGPTLs do
      not bind to either the angiopoietin receptor Tie2 or the related protein Tie1,
      indicating that these ligands function differently from angiopoietins. Like
      angiopoietins, some ANGPTLs potently regulate angiogenesis, but ANGPTL3, -4 and
      ANGPTL6/angiopoietin-related growth factor (AGF) directly regulate lipid, glucose
      and energy metabolism independent of angiogenic effects. Recently, we found that
      ANGPTL2 is a key adipocyte-derived inflammatory mediator that links obesity to
      systemic insulin resistance. In this minireview, we focus on the roles of ANGPTL2
      and ANGPTL6/AGF in obesity and related metabolic diseases, and discuss the
      possibility that both could function as molecular targets for the prevention and
      treatment of obesity and metabolic diseases.

PMID- 21182597
TI  - Pathogenesis of gestational urinary tract infection: urinary obstruction versus
      immune adaptation and microbial virulence.

PMID- 21182598
TI  - Another kind of ethics: from corrections to retractions.

PMID- 21182599
TI  - Resuscitation guidelines 2010: a scientific consensus.

PMID- 21182600
TI  - The effect of anaesthesia and aortic clamping on cardiac output measurement using
      arterial pulse power analysis during aortic aneurysm repair.
AB  - The LiDCO plus monitor (LiDCO Ltd, Cambridge, UK) uses pulse contour analysis of
      the arterial pressure waveform to indicate changes in stroke volume and cardiac
      output. Calibration against a lithium indicator dilution method is required to
      permit display of absolute values in addition to trends. The effect of
      haemodynamic changes during anaesthesia and surgery on this calibration factor
      has not previously been studied. Therefore, we investigated whether it remained
      constant during elective abdominal aortic aneurysm surgery in 15 patients.
      Comparison between the calibration factor values at different time points was
      made by repeated recalibration throughout the peri-operative period. Calibration
      factor increased by a mean of 53% after anaesthesia (epidural plus general) (p =
      0.03) and decreased by a mean of 40% after aortic clamping (p = 0.0001).
      Recalibration should be undertaken after induction of anaesthesia and after
      aortic clamping if absolute values of cardiac output and stroke volume are
      required.

PMID- 21182601
TI  - Comparison of phenylephrine hydrochloride and mephentermine sulphate for
      prevention of post spinal hypotension.
AB  - This study compared the effects of intravenous infusions of phenylephrine and
      mephentermine on the prevention of maternal hypotension and neonatal outcome in
      patients receiving spinal anaesthesia for caesarean section. Sixty ASA 1-2
      patients with term, uncomplicated singleton pregnancy undergoing caesarean
      section under spinal anaesthesia were randomly divided into two groups of 30
      each, to receive a prophylactic intravenous infusion of either phenylephrine or
      mephentermine. The incidence of hypotension was statistically similar in the two
      groups. However, in patients receiving phenylephrine, 7 (23%) developed
      bradycardia and 6 (20%), reactive hypertension. Neonatal outcome, in terms of
      Apgar scores and umbilical artery pH, was similar in both the groups. To
      conclude, phenylephrine and mephentermine infusions are equally effective in
      preventing post spinal hypotension in patients undergoing caesarean section and
      are associated with a similar neonatal outcome.

PMID- 21182602
TI  - Efficacy of mirtazapine in preventing intrathecal morphine-induced nausea and
      vomiting after orthopaedic surgery*.
AB  - Nausea and vomiting are frequent complications of intrathecal morphine. In this
      randomised, double-blind trial, we tested the efficacy of mirtazapine, an
      antidepressant that blocks receptors associated with vomiting, on the incidence
      of nausea and vomiting after intrathecal morphine. One hundred patients receiving
      spinal anaesthesia for lower limb surgery were assigned equally to take either an
      orally disintegrating form of 30 mg mirtazapine or matching placebo 1 h before
      surgery. Spinal anaesthesia was performed by injection of 15 mg isobaric
      bupivacaine 0.5% along with 0.2 mg preservative-free morphine. Nausea and
      vomiting were evaluated 3, 6, 12, 18 and 24 h after intrathecal morphine
      administration. The incidence of nausea and vomiting was significantly lower in
      patients receiving mirtazapine compared with placebo (26.5% vs 56.3%,
      respectively; p = 0.005). The mean (SD) onset time of postoperative nausea and
      vomiting was significantly delayed in mirtazapine patients: 9.4 (2.5) vs 5.2
      (1.8) h, respectively; p < 0.0001. The severity of nausea and vomiting was also
      decreased after mirtazapine at the 3-6 h and 6-12 h periods. Our data indicate
      that pre-operative mirtazapine decreases the incidence, delays the onset and
      reduces the severity of nausea and vomiting induced by intrathecal morphine in
      patients undergoing spinal anaesthesia.

PMID- 21182603
TI  - The analysis of variance in anaesthetic research: statistics, biography and
      history.
AB  - Multiple t-tests (or their non-parametric equivalents) are often used erroneously
      to compare the means of three or more groups in anaesthetic research. Methods for
      correcting the p value regarded as significant can be applied to take account of
      multiple testing, but these are somewhat arbitrary and do not avoid several
      unwieldy calculations. The appropriate method for most such comparisons is the
      'analysis of variance' that not only economises on the number of statistical
      procedures, but also indicates if underlying factors or sub-groups have
      contributed to any significant results. This article outlines the history,
      rationale and method of this analysis.

PMID- 21182604
TI  - Needlestick injuries.

PMID- 21182605
TI  - Need(le)less confusion.

PMID- 21182606
TI  - Needlestick injury.

PMID- 21182607
TI  - Testing of incapacitated patients for blood-borne disease is ethical.

PMID- 21182608
TI  - Cell salvage and leucocyte depletion filters.

PMID- 21182609
TI  - Fibrinogen concentrate use during major obstetric haemorrhage.

PMID- 21182610
TI  - Amniotic fluid embolism diagnosed by fibre-optic bronchoscopy.

PMID- 21182611
TI  - Aspiration testing and epidural filters.

PMID- 21182612
TI  - A two-bougie technique for safer oro- to nasotracheal tube exchange in a
      difficult airway.

PMID- 21182613
TI  - Tracheostomy ventilation using a laryngeal mask as a 'bridge to extubation'.

PMID- 21182614
TI  - Cartoons and the art of paediatric inhalational induction.

PMID- 21182616
TI  - Notice of retraction.

PMID- 21182615
TI  - Torsades de pointes: provoked by refeeding?

PMID- 21182627
TI  - Platelet storage and adverse transfusion outcomes: old platelets?

PMID- 21182628
TI  - Platelet transfusions to HLA-immunized recipients: how to be or not to be
      matched.

PMID- 21182629
TI  - A prospective bonus of platelet storage additive solutions: a reduction in
      biofilm formation and improved bacterial detection during platelet storage.

PMID- 21182630
TI  - Transfusion medicine illustrated. Erythrophagocytosis in cold agglutinin disease.

PMID- 21182632
TI  - Usefulness of platelet (PLT) pathogen inactivation technology: a case of
      Sphingomonas paucimobilis inactivation in an apheresis PLT unit.

PMID- 21182633
TI  - Therapeuticefficacy of platelet transfusion in patients with acute leukemia.

PMID- 21182635
TI  - The rheologic properties of leukoreduced red blood cells.

PMID- 21182637
TI  - Re: "WHO evaluation of the serologic assays for Chagas disease".

PMID- 21182639
TI  - Allergic contact dermatitis to chlorhexidine in a very young child.
AB  - Allergic contact dermatitis to chlorhexidine is an unusual condition, with
      sensitization in childhood rarely reported. We report the observation of allergic
      contact dermatitis to chlorhexidine in a 23-month-old boy.

PMID- 21182640
TI  - Superficial granulomatous pyoderma: a case in an 11-year-old girl and review of
      the literature.
AB  - Superficial granulomatous pyoderma is a rare entity thought to be a variant of
      pyoderma gangrenosum and is often mistaken for classic pyoderma gangrenosum.
      Superficial granulomatous pyoderma has mainly been described in adults. We
      describe a case of Superficial granulomatous pyoderma in an 11-year-old girl and
      present a review of the literature. Superficial granulomatous pyoderma maintains
      clinical and histopathologic characteristics distinct from classic pyoderma
      gangrenosum and has a more favorable prognosis. It is often responsive to
      conservative treatment.

PMID- 21182641
TI  - Porokeratotic eccrine duct and hair follicle nevus (PEHFN) associated with
      keratitis-ichthyosis-deafness (KID) syndrome.
AB  - Porokeratotic eccrine ostial and dermal duct nevus is a rare hamartomatous
      malformation, histologically characterized by cornoid lamellae overlying dilated
      eccrine ostia. The nevus most commonly presents in the form of multiple filiform
      keratotic spines in a linear arrangement, usually on the distal extremities.
      Porokeratotic eccrine and hair follicle nevus is thought to be a variant of
      porokeratotic eccrine ostial and dermal duct nevus that additionally involves
      hair follicle infundibula. We report a case of widespread Porokeratotic eccrine
      and hair follicle nevus that developed in a 15-year-old woman with keratitis
      ichthyosis-deafness syndrome.

PMID- 21182642
TI  - Results of Goeckerman treatment for psoriasis in children: a 21-year
      retrospective review.
AB  - Goeckerman treatment has been used for the management of widespread psoriasis in
      children for several decades at Mayo Clinic. We aimed to review our institutional
      experience with the effectiveness of Goeckerman treatment for psoriasis in
      children. We retrospectively reviewed the records of pediatric patients who
      underwent Goeckerman treatment over a 21-year period (1983-2003). The main
      outcome measure was improvement in psoriasis. During the study period, 65
      children received Goeckerman treatment for predominantly widespread, recalcitrant
      psoriasis. The mean age was 11.6 years (range, 3 mos to 18 yrs), and the female
      to-male ratio was 2:1. Psoriasis improved in all patients: 55 patients (85%) had
      >80% clearance of their psoriasis. The only adverse effect was folliculitis,
      occurring in 27 patients (42%). Mean duration of follow-up was 2.6 years (range,
      17 days-18.2 yrs); average duration of remission was 2.6 years (range, 2 mos
      12.79 yrs). Goeckerman treatment is an effective treatment for widespread
      psoriasis in children.

PMID- 21182643
TI  - Pedunculated lesion of the scalp with surrounding long, dark hair in a newborn.
      Nevus sebaceus of Jadassohn with the hair collar sign.

PMID- 21182644
TI  - A large tumor on the scalp of a newborn. Solitary myofibroma.

PMID- 21182645
TI  - Generalized scaling and redness in a 2-month-old boy. Crusted (Norwegian) scabies
      (CS).

PMID- 21182646
TI  - Morphea affecting a father and son.
AB  - Morphea, also known as localized scleroderma, is characterized by firm plaques
      that can occur anywhere on the body. Reports of familial morphea are rare, and we
      report an unusual case of morphea affecting both a father and a son.

PMID- 21182647
TI  - Photodynamic therapy of condyloma acuminatum in a child.
AB  - Conventional therapies for condyloma acuminatum in children are often associated
      with unsatisfactory response and high recurrence rate. Here, we present a 9-year
      old girl with vulvar condyloma acuminatum successfully treated with topical 5
      aminolaevulinic acid mediated photodynamic therapy. 5-aminolaevulinic acid
      mediated photodynamic therapy is a promising therapy for condylomata acuminata in
      children.

PMID- 21182648
TI  - "Hairy" granular cell tumor.
AB  - The occurrence of a solitary subcutaneous granular cell tumor characterized by
      overlying hypertrichosis in a child is reported. Granular cell tumor should be
      included in the differential diagnosis of cutaneous neoplasms associated
      hypertrichosis in the pediatric patient.

PMID- 21182649
TI  - Eccrine angiomatous hamartoma in a child.
AB  - Eccrine angiomatous hamartoma (EAH) is a rare, benign malformation characterized
      by both eccrine and vascular components. It usually presents at birth or during
      early infancy and childhood as a nodule or a plaque, usually solitary, involving
      acral skin. Eccrine angiomatous hamartoma is usually asymptomatic, although focal
      hyperhidrosis, hypertrichosis, and pain can be observed. We report an additional
      case of this rare entity presenting in a 14-year-old boy.

PMID- 21182650
TI  - Diarrhea associated with propranolol treatment for hemangioma of infancy (HOI).

PMID- 21182651
TI  - Acute generalized exanthematous pustulosis or toxic epidermal necrolysis?

PMID- 21182652
TI  - Papular xanthoma.

PMID- 21182654
TI  - Abstracts of Gastroenterology in Asia Pacific - Excellence in the New Decade.
      September 19-22, 2010. Kuala Lumpur, Malaysia.

PMID- 21182656
TI  - Abstracts of Australian Gastroenterology Week 2010. October 20-23, 2010.
      Broadbeach, Queensland, Australia.

PMID- 21182657
TI  - Real and virtual issues in optometry.

PMID- 21182658
TI  - Intraocular lenses in the 21st century.

PMID- 21182659
TI  - Accommodating intraocular lenses: a review of design concepts, usage and
      assessment methods.
AB  - The correction of presbyopia and restoration of true accommodative function to
      the ageing eye is the focus of much ongoing research and clinical work. A range
      of accommodating intraocular lenses (AIOLs) implanted during cataract surgery has
      been developed and they are designed to change either their position or shape in
      response to ciliary muscle contraction to generate an increase in dioptric power.
      Two main design concepts exist. First, axial shift concepts rely on anterior
      axial movement of one or two optics creating accommodative ability. Second,
      curvature change designs are designed to provide significant amplitudes of
      accommodation with little physical displacement. Single-optic devices have been
      used most widely, although the true accommodative ability provided by forward
      shift of the optic appears limited and recent findings indicate that alternative
      factors such as flexing of the optic to alter ocular aberrations may be
      responsible for the enhanced near vision reported in published studies.
      Techniques for analysing the performance of AIOLs have not been standardised and
      clinical studies have reported findings using a wide range of both subjective and
      objective methods, making it difficult to gauge the success of these implants.
      There is a need for longitudinal studies using objective methods to assess long
      term performance of AIOLs and to determine if true accommodation is restored by
      the designs available. While dual-optic and curvature change IOLs are designed to
      provide greater amplitudes of accommodation than is possible with single-optic
      devices, several of these implants are in the early stages of development and
      require significant further work before human use is possible. A number of
      challenges remain and must be addressed before the ultimate goal of restoring
      youthful levels of accommodation to the presbyopic eye can be achieved.

PMID- 21182660
TI  - Correctable visual impairment among people with diabetes in Hong Kong.
AB  - BACKGROUND: the prevalence of visual impairment is known to be higher in a
      diabetic population than in a non-diabetic population. How much of this visual
      impairment may be attributed to uncorrected refractive error is unclear. This
      study examined the prevalence of visual impairment in a Hong Kong diabetic
      population to determine the proportion of the visual impairment that could be
      corrected with prescription spectacles. METHODS: patients with type 2 diabetes
      mellitus (T2DM) were recruited as subjects for this study. All subjects underwent
      a standardised diabetic retinopathy screening that included measurement of
      presenting distant vision, biomicroscopic examination of the anterior eye and a
      retinal examination. For those subjects whose visual acuity was worse than 6/9.5,
      autorefraction was performed. In this study, we classified visual impairment into
      three categories: no visual impairment (visual acuity in the better eye better
      than or equal to 6/18), mild visual impairment (visual acuity in the better eye
      between 6/18 and 6/60) and severe visual impairment (visual acuity in the better
      eye less than or equal to 6/60). RESULTS: for the 2,301 subjects who participated
      in this study, the mean age at examination was 61.4 +/- 10.5 years (range, 23 to
      92 years). Regarding visual acuity, 11.3 per cent (259/2,301) of subjects had
      visual impairment with 10.6 per cent being mild (244/2,301) and 0.7 per cent
      severe (15/2,301). After correction with a prescription determined by
      autorefraction, the prevalence of visual impairment dropped to 4.0 per cent
      (91/2,301). Nearly 70 per cent (168/259) of visual impairment was correctable by
      prescription spectacles and 21.6 per cent (56/259) of subjects were likely to
      benefit from cataract surgery. CONCLUSION: for our sample of diabetic patients,
      nearly 70 per cent of the visual impairment could be remedied by a spectacle
      correction. In the care of the diabetic eye, eye-care providers should not focus
      solely on diabetic retinopathy. The quality of life in people with T2DM can be
      improved simply by eliminating uncorrected refractive errors.

PMID- 21182661
TI  - Anti-glaucoma medication exposure in pregnancy: an observational study and
      literature review.
AB  - BACKGROUND: there are limited data about the effects of anti-glaucoma drugs on
      pregnancy. The purpose of this study was to observe pregnancies exposed to anti
      glaucoma medications. METHODS: six pregnant glaucomatous patients referred to the
      glaucoma clinic after their first trimesters were advised to continue their
      medications. In one patient who was on oral acetazolamide, the drug was
      substituted with topical medications. In the last month of pregnancy
      acetazolamide was started and all topical medications were stopped. The control
      group comprised 24 individuals with no systemic disease or exposure to
      medications and with comparable age and gestational age on delivery. Pregnancy
      and delivery complications, Apgar scores at one and five minutes, birth weight,
      congenital anomalies and psychophysical development of children up to two years
      of age were evaluated. RESULTS: the mean age of the patients was 28.17 years with
      mean gestational age on delivery of 38.80 weeks. Low birth weight was more common
      in the case group (p = 0.041). No other side-effects were observed. The one
      minute Apgar scores were nine in all newborns and improved to 10 at five minutes.
      The psychophysical development of all children was normal up to two years after
      birth. CONCLUSIONS: analysis of pregnancy outcome of six mothers taking topical
      glaucoma medications showed no adverse effects apart from a small but
      statistically significant increased risk of having low birth weight.

PMID- 21182662
TI  - Co-existence of Staphylococcus spp and Stenotrophomonas maltophilia infection in
      persistent endophthalmitis after cataract surgery.

PMID- 21182665
TI  - A call to action for conserving biological diversity in the face of climate
      change.

PMID- 21182666
TI  - Metaphor and the idea of a dominant conservation ethic.

PMID- 21182667
TI  - Application of modified threat reduction assessments in Lebanon.
AB  - Worldwide efforts have concentrated on developing monitoring methods that would
      enhance the assessment of progress toward achieving the 2010 conservation
      objectives of the Convention on Biological Diversity. Threat reduction assessment
      is one such method. It provides an indirect measure of the effects of a
      conservation project by evaluating changes in human-induced direct threats to
      protected areas. We applied modified threat reduction assessments and the 2008
      International Union for Conservation of Nature standardized lexicon for
      classification of threats to Horsh Ehden and Al-Shouf Cedar nature reserves in
      Lebanon. Our goal was in part to test the suitability of this tool for improving
      monitoring and management effectiveness of protected forests in Lebanon. In Horsh
      Ehden, composite threats decreased by 24% from 1997 to 2002, and then increased
      from 2002 to 2009 by 78% in the core area of the reserve and by 118% in the
      reserve's buffer zone (surrounds core area, conservation and recreational
      activities allowed). In Al-Shouf Cedar reserve threats decreased by 51% from 2006
      to 2009. Management teams from both reserves have integrated the use of this
      method to prioritize actions for new management plans. We believe that in Lebanon
      and other countries with limited resources and weak monitoring programs or that
      are experiencing political instability threat reduction assessments could be used
      to improve the effectiveness of protected areas management.

PMID- 21182668
TI  - Evaluating private land conservation in the Cape Lowlands, South Africa.
AB  - Evaluation is important for judiciously allocating limited conservation resources
      and for improving conservation success through learning and strategy adjustment.
      We evaluated the application of systematic conservation planning goals and
      conservation gains from incentive-based stewardship interventions on private land
      in the Cape Lowlands and Cape Floristic Region, South Africa. We collected
      spatial and nonspatial data (2003-2007) to determine the number of hectares of
      vegetation protected through voluntary contractual and legally nonbinding
      (informal) agreements with landowners; resources spent on these interventions;
      contribution of the agreements to 5- and 20-year conservation goals for
      representation and persistence in the Cape Lowlands of species and ecosystems;
      and time and staff required to meet these goals. Conservation gains on private
      lands across the Cape Floristic Region were relatively high. In 5 years, 22,078
      ha (27,800 ha of land) and 46,526 ha (90,000 ha of land) of native vegetation
      were protected through contracts and informal agreements, respectively. Informal
      agreements often were opportunity driven and cheaper and faster to execute than
      contracts. All contractual agreements in the Cape Lowlands were within areas of
      high conservation priority (identified through systematic conservation planning),
      which demonstrated the conservation plan's practical application and a high level
      of overlap between resource investment (approximately R1.14 million/year in the
      lowlands) and priority conservation areas. Nevertheless, conservation agreements
      met only 11% of 5-year and 9% of 20-year conservation goals for Cape Lowlands and
      have made only a moderate contribution to regional persistence of flora to date.
      Meeting the plan's conservation goals will take three to five times longer and
      many more staff members to maintain agreements than initially envisaged.

PMID- 21182670
TI  - The hybrid algorithm (Hbmr) to fight against blood doping in sports.

PMID- 21182671
TI  - Comment on '"The hybrid algorithm (Hbmr) to fight against blood doping in
      sports"' by F. Sanchis-Gomar et al.

PMID- 21182673
TI  - Detection of corneodesmosin on the surface of stratum corneum using atomic force
      microscopy.
AB  - Corneodesmosin, a protein known to be present in the stratum corneum (SC), plays
      an important role in its physical integrity. Here, a specific antibody to
      corneodesmosin was tethered via a flexible linker to an atomic force microscopy
      tip, and the interaction forces between this tip and the surface of the SC were
      successfully measured. Using the recently developed technique of simultaneous
      topography and recognition imaging, we were able to map the distribution of
      corneodesmosin on the surface of the SC at the nanoscale.

PMID- 21182687
TI  - Development and structure of drinking water biofilms and techniques for their
      study.
AB  - Drinking water systems are known to harbour biofilms, even though these
      environments are oligotrophic and often contain a disinfectant. Control of these
      biofilms is important for aesthetic and regulatory reasons. Study of full-scale
      systems has pointed to several factors controlling biofilm growth, but cause-and
      effect relationships can only be established in controlled reactors. Using
      laboratory and pilot distribution systems, along with a variety of bacterial
      detection techniques, insights have been gained on the structure and behaviour of
      biofilms in these environments. Chlorinated biofilms differ in structure from non
      chlorinated biofilms, but often the number of cells is similar. The number and
      level of cellular activity is dependent on the predominant carbon source. There
      is an interaction between carbon sources, the biofilm and the type of pipe
      material, which complicates the ability to predict biofilm growth. Humic
      substances, which are known to sorb to surfaces, appear to be a usable carbon
      source for biofilms. The finding offers an explanation for many of the puzzling
      observations in full scale and laboratory studies on oligotrophic biofilm growth.
      Pathogens can persist in these environments as well. Detection requires methods
      that do not require culturing.

PMID- 21182688
TI  - The role of exopolysaccharides in dual species biofilm development.
AB  - A plasmid encoding the green fluorescent protein (GFP) of Aequorea victoria was
      transformed into a biofilm-forming strain of Enterobacter agglomerans originally
      isolated from an industrial environment. The transformed strain, EntGFP, could
      then be identified in dual species biofilms by direct visualization, plate counts
      and quantitiative fluorescence measurements. A variety of cell constituents and
      products may be involved in the adhesion and accumulation process and
      exopolysaccharides (EPS) represent one of these factors. The involvement of EPS
      in the initial adhesion events and the role in dual species biofilm development
      was investigated. Cells of EntGFP and Klebsiella pneumoniae Gl interact forming
      biofilms more successfully in a mixture than in isolation. The co-resistance
      results in enhanced biofilm formation and increased resistance to disinfection.
      Microscopic examination showed that the two species were often closely juxtaposed
      in microcolonies, suggesting the interactions involve surface-associated
      macromolecules. Fluorescence was used to measure the adhesion of EntGFP cells to
      Kleb, pneumoniae Gl (Gl) EPS. The results showed EntGFP adhered better to Gl EPS
      that Ent EPS. Polysaccharde depolymerases isolated from a bacteriophage for Ent.
      agglomerans were used to degrade Ent EPS specifically. Following polysaccharase
      treatment, the adhaesion of EntGFP to Gl cells was reduced. This suggests both
      types of EPS mediate adhesion. The two types of EPS were dissolved in
      dimethylsulphoxide and when mixed, their viscosity increased, reaching a maximum
      after ~+40 min. This may partially explain the increased protection of dual
      species biofilms from disinfectants. The depolymerases were used to treat dual
      species biofilms and this resulted in the effective removal of both species from
      the surface. This may suggest Ent contributes more EPS to the biofilm matrix. The
      EPS play an important role in EntGFP and Gl dual species biofilm formation both
      as adhesins and as the EPS interact, changing their physical properties.

PMID- 21182689
TI  - Influence of hydrodynamics and nutrients on biofilm structure.
AB  - Hydrodynamic conditions control two interlinked parameters; mass transfer and
      drag, and will, therefore, significantly influence many of the processes involved
      in biofilm development. The goal of this research was to determine the effect of
      flow velocity and nutrients on biofilm structure. Biofilms were grown in square
      glass capillary flow cells under laminar and turbulent flows. Biofilms were
      observed microscopically under flow conditions using image analysis. Mixed
      species bacterial biofilms were grown with glucose (40 mg/l) as the limiting
      nutrient. Biofilms grown under laminar conditions were patchy and consisted of
      roughly circular cell clusters separated by interstitial voids. Biofilms in the
      turbulent flow cell were also patchy but these biofilms consisted of patches of
      ripples and elongated 'streamers' which oscillated in the flow. To assess the
      influence of changing nutrient conditions on biofilm structure the glucose
      concentration was increased from 40 to 400 mg/l on an established 21 day old
      biofilm growing in turbulent flow. The cell clusters grew rapidly and the
      thickness of the biofilm increased from 30 MU to 130 MU within 17 h. The ripples
      disappeared after 10 hours. After 5 d the glucose concentration was reduced back
      to 40 mg/l. There was a loss of biomass and patches of ripples were re
      established within a further 2 d.

PMID- 21182690
TI  - The relationship between pipe material and biofilm formation in a laboratory
      model system.
AB  - The aim of this study was to compare biofilm accumulation and heterotrophic
      bacterial diversity on three pipe materials-cast iron, medium density
      polyethylene (MDPE), and unplasticised polyvinyl chloride (uPVC) - using a
      laboratory model system run over a short period (21 d) and a longer period (7
      months). Newly Modified Robbins Devices (nMRD) were run in parallel, each
      containing 25 discs of one material with cold tap water flowing through the
      devices at 3 ml min(-1) (Reynolds Number 9.05) for 21 d. The numbers of bacteria
      on each material increased exponentially between 0 and 11 d when the biofilm
      viable count remained constant. The mean doubling times of the heterotrophic
      population on the materials during the exponential phase was 13.2 h for cast iron
      and 15.6 h for MDPE and uPVC. The same experiment was repeated under different
      environmental conditions with a lower temperature, higher free chlorine and lower
      number of organisms ml(-1) of incoming water. The exponential phase lengthened to
      16 d but the steady state count remained the same. The mean viable count after 21
      d and after 7 months was on average 97% higher on cast iron than on the other
      materials. Very few different colony types were isolated from each material with
      the largest number (nine) recovered from cast iron. The numbers of planktonic
      bacteria in the effluent water leaving each of the nMRDs directly correlated with
      the numbers in the biofilm phase on each of the materials. In addition the
      distribution and thickness of the biofilms on the MDPE and uPVC were observed
      using confocal scanning laser microscopy. In conclusion, MDPE and uPVC support
      the lowest numbers of bacteria in a steady state biofilm in the short term (21 d)
      and over a longer term (7 months). The diversity of heterotrophic bacteria was
      greatest on cast iron.

PMID- 21182691
TI  - Potential for biofilm development in drinking water distribution systems.
AB  - Regrowth of micro-organisms in drinking water distribution systems is caused by
      the utilisation of biodegradable compounds which are either present in treated
      water or originate from materials in contact with drinking water. In the
      Netherlands most drinking water is distributed without disinfectant residual and
      regrowth is limited by achieving biostable drinking water. A combination of
      methods is used to assess the biostability of drinking water. These methods are:
      (1) determination of the concentration of easily assimilable organic carbon
      (AOC); and (2) assessment of the biofilm formation rate (BFR). Assimilated
      organic carbon concentrations in drinking water in the Netherlands range from a
      few MUg C/l in slow sand filtrates and in ground water supplies to values of ~ 50
      MUg C/l in supplies using ozonation in water treatment. Biofilm formation rate
      values were found to range from < 1 pg ATP/cm(2)/d in supplies using anaerobic
      ground water as the source. Increase of heterotrophic plate counts is limited at
      AOC values below 10 MUg C/l. At BFR values below 10 pg ATP/cm(2)/d the risk of
      exceeding the guideline value for aeromonads (90 percentile < 200 c.f.u./100 ml)
      is less than 20%. Calculations based on the decrease of the AOC concentration
      observed in distributions systems confirm that very low concentrations of AOC can
      cause considerable biofilm formation on the pipe wall. The methods for assessing
      the biostability of drinking water combine with the assessment of the Biofilm
      Formation Potential of materials in contact with drinking water, thus providing a
      framework, the Unified Biofilm Approach, for evaluating the biostability of
      drinking water and materials.

PMID- 21182692
TI  - Bacterial colonization and biofilm development on minimally processed vegetables.
AB  - Bacterial biofilms have been observed and reported on food and food-processing
      surfaces and can contribute to increased risks for product quality and food
      safety. The colonization of fruit and vegetables by pectynolitic bacteria like
      Pseudonomas fluorescens attributable to conditions such as soft rot, can also
      manifest as biofilms. A developed biofilm structure can provide a protective
      environment for pathogens such as Listeria monocytogenes reducing the
      effectiveness of sanitisers and other inhibitory agents. Understanding the
      colonization of bacteria on leaf surfaces is essential to the development of a
      better understanding of the leaf ecology of vegetable products. Studies of
      microbial colonization of leaf surfaces have been conducted using SEM and more
      recently using confocal microsocpy techniques. In the current study, a Leica TCS
      NT laser scanning confocal microscope was used to investigate biofilm formation
      using vital fluorescence staining on intact vegetable leaves. Reflection contrast
      and fluorescence three-dimensional imaging successfully delineated bacterial and
      biofilm morphology without disturbing the bacterial or leaf surface structure.
      The results demonstrate the presence and development of biofilm on the surface of
      lettuce. The biofilms appeared to originate on the cuticle in distinct micro
      environments such as in the natural depression of the stomata, or in the
      intercellular junction. Bacteria also adhered to and developed biofilm colonies
      within an hour of contact and with clean stainless steel surfaces. Our study
      investigates the progression of biofilm formation from leaf colonization, and
      will assist in characterising the critical mechanisms of plant/host interaction
      and facilitate the development of improved preservation, sanitising and packaging
      strategies for minimally processed vegetable products.

PMID- 21182693
TI  - Biofilms in drinking water systems: a possible reservoir for Helicobacter pylori.
AB  - A laboratory model system was utilised to investigate the persistence of
      Helicobacter pylori in mixed-species heterotrophic biofilms. A single-stage
      continuous culture vessel was linked to a modified-Robbins device (mRD)
      incorporating removable stainless steel coupons. The system was innoculated with
      H. pylori (NCTC 11637) and the fate of the organism monitored by polymerase chain
      reaction (PCR) analysis. Helicobacter pylori was detected in biofilm material for
      a period of up to 192 h. Theoretical washout would have occurred at around 48 h
      thus detection of H. pylori for a prolonged period after theoretical washout
      suggested that the organism possessed the ability to persist in the mixed-species
      heterotrophic biofilm. Preliminary studies using heat-inactivated H. pylori
      showed that the organism was not detected in biofilm material at any time post
      challenge suggesting that the persistence of H. pylori in such material was a
      phenomenon requiring the organism to be in a viable state. Further investigations
      to assess the biological basis for the association of H. pylori with drinking
      water biofilms and the risk that this may pose to public health are being
      undertaken.

PMID- 21182694
TI  - Mycobacterium fortuitum and Mycobacterium chelonae biofilm formation under high
      and low nutrient conditions.
AB  - The rapidly growing mycobacteria (RGM) are broadly disbursed in the environment.
      They have been recovered from freshwater, seawater, wastewater and even potable
      water samples and are increasingly associated with non-tuberculous mycobacterial
      disease. There is scant evidence that non-tuberculous mycobacteria (NTM) and RGM
      form biofilms. Therefore, an experimental system was designed to assess the
      ability of RGM to form biofilms under controlled laboratory conditions. A flat
      plate reactor flow cell was attached to either a high or low nutrient reservoir
      and monitored by image analysis over time. Two surfaces were chosen for
      assessment of biofilm growth: silastic which is commonly used in medical settings
      and high density polyethylene (HDPE) which is prevalent in water distribution
      systems. The results show that Mycobacterium fortuitum and M. chelonae formed
      biofilms under both high and low nutrient conditions on both surfaces studied.
      These results suggest that RGM may form biofilms under a variety of conditions in
      industrial and medical environments.

PMID- 21182695
TI  - Faecal indicator impacts on recreational waters: budget studies and diffuse
      source modelling.
AB  - A series of investigations are underway which have quantified the contribution of
      faecal indicators delivered to nearshore coastal waters from the sewerage system
      and riverine inputs. Studies have been completed in Jersey, Staithes, Yorkshire,
      South Wales and the North-west. The research protocols have involved
      quantification of high and low flow faecal indicator delivery from the sewerage
      system and riverine sources as well as construction of nonpoint source models
      designed to predict faecal indicator delivery from diffuse, catchment sources.
      These investigations suggest a dynamic, but predictable, balance between inputs
      from the sewerage system and from 'catchment' sources. The sewerage system
      dominates during low flow conditions but is often overtaken by riverine inputs
      during high flow conditions after rainfall. Many bathing beach locations exhibit
      non-compliance after rainfall when stream inputs, rather than sewerage inputs,
      commonly dominate. The implications of this input pattern is that routine
      monitoring data may not provide information relevant to new infrastructure
      planning designed to achieve bathing beach compliance. This suggests that the
      present scientific information base is insufficient to underpin the extensive UK
      infra-structure investment programmes designed to ensure compliance with existing
      EU Directive 76/160/EEC standards. Furthermore, results to date, suggest that
      management attention must expand from its historical focus on infra-structure
      provision to incorporate diffuse sources of faecal indicator loading which
      present a new set of management and modelling challenges.

PMID- 21182696
TI  - Soil: the environmental source of Escherichia coli and Enterococci in Guam's
      streams.
AB  - We have previously documented that faecal indicator bacteria (Escherichia coli,
      faecal coliform, enterococci) recommended by the U.S. Environmental Protection
      Agency (USEPA) to establish recreational water quality standards are naturally
      found in high concentrations in the surface and subsurface of soils in Hawaii.
      Rain, the source of all streams in Hawaii, washes the soil sources of faecal
      bacteria into all the streams of Hawaii, at concentrations which consistently
      exceed the USEPA recreational water quality standards. The objective of this
      study was to test the hypothesis that faecal bacteria are able to establish
      themselves in the soil environments of tropical islands by conducting the same
      study in Guam, a tropical pacific island with warmer temperatures and higher
      humidity than Hawaii. The same methods and study design used in Hawaii was used
      in Guam. The results of the study conducted in Guam revealed that all streams
      contain consistently high concentrations of faecal coliform, E. coli, and
      enterocci which exceeded the old USEPA recreational water quality standard of 200
      faecal coliform/100 ml as well as the new water quality standards of 126 E.
      coli/100 ml or 33 enterococci/100 ml. These same faecal indicator bacteria were
      recovered in high concentrations in surface and subsurface (18-36 cm depth) soil
      samples in Guam. Limited coastal water analysis showed that most coastal marine
      waters contain low concentrations of faecal bacteria but coastal waters impacted
      by stream run-off showed elevated levels of faecal bacteria. The results of this
      study support the hypothesis that environmental conditions in the tropical areas
      of the world can support the growth and establishment of populations of faecal
      bacteria in the soil. Thus, soil becomes an environmental, non-faecal source of
      faecal indicator bacteria. These results indicate that USEPA water quality
      standards may not be directly applicable to tropical island environments.

PMID- 21182697
TI  - Distribution of the human faecal bacterium Bacteroides fragilis, its
      bacteriophages and their relationship to current sewage pollution indicators in
      bathing water.
AB  - Although several bacteria are currently used as possible indicators of human
      pathogens in sewage-polluted sea water, they are often viewed as inadequate and
      especially inadequate as indicators of viral pathogens. This study investigates
      the distribution of Bacteroides fragilis and closely related Bacteroides spp. and
      their associated bacteriophages in sea water frequently used for recreational
      purposes. These organisms may provide a potentially more appropriate indicator.
      Bacteroides fragilis is one of about 10 species which are loosely placed together
      in the 'B. fragilis' group. Samples down-current from a sewage outfall were
      examined for the presence of B. fragilis group organisms and associated
      bacteriophages. Numbers were correlated with current bacterial and possible viral
      indicators at these sites. These B. fragilis group isolates were used as hosts to
      successfully isolate bacteriophages. The host range of these bacteriophages was
      investigated. It is hoped to expand this study by using these B. fragilis group
      hosts and their bacteriophages to identify a more suitable, European-wide,
      indicator of bacterial pathogens which can also be used to detect bacteriophages
      which are suitable as viral indicators.

PMID- 21182698
TI  - Non-compliance of beaches with the EU directives of bathing water quality:
      evidence of non-point sources of pollution in Morecambe Bay.
AB  - Morecambe's three EU designated bathing beaches frequently fail the EU
      directives, even after a state of the art sewage treatment plant has become
      operational. We have been using conventional microbiology to look at the
      seasonality and distribution of indicator and pathogenic bacteria in Morcambe Bay
      and using molecular methods (polymerase chain reaction (PCR) and pulse field gel
      electrophoresis (PFGE)) to investigate the pathways by which pathogens reach the
      bathing waters. We will present data for Morecambe Bay which show that: 1.
      Failures and passes appear to be associated with the prevailing climatic
      conditions. 2. Indicator bacteria may not always be derived from sewage
      effluents. 3. Not all pathogens are distributed in the same way as indicator
      bacteria. 4. Pathogens such as Campylobacter are as likely to come from birds as
      from sewage.

PMID- 21182699
TI  - The biochemical diversity of life near and above 100 degrees C in marine
      environments.
AB  - Hyperthermophilic micro-organisms grow at temperatures above 90  degrees C with a
      current upper limit of 113  degrees C. They are a recent discovery in the
      microbial world and have been isolated mainly from marine geothermal
      environments, which include both shallow and deep sea hydrothermal vents. By 16S
      rRNA analyses they are the most slowly evolving of all extant life forms, and all
      but two of the nearly 20 known genera are classified as Archaea (formerly
      Archaebacteria). Almost all hyperthermophiles are strict anaerobes. They include
      species of methanogens, iron-oxidizers and sulphate reducers, but the majority
      are obligate heterotrophs that depend upon the reduction of elemental sulphur (S
      degrees ) to hydrogen sulphide for significant growth. The heterotrophs utilize
      proteinaceous materials as carbon and energy sources, although a few species are
      also saccharolytic. A scheme for electron flow during the oxidation of
      carbohydrates and peptides and the reduction of S degrees  has been proposed. Two
      S degrees -reducing enzymes have been purified from the cytoplasm of one
      hyperthermophile (T(opt) 100  degrees C) that is able to grow either with and
      without S degrees . However, the mechanisms by which S degrees  reduction is
      coupled to energy conservation in this organism and in obligate S degrees 
      reducing hyperthermophiles is not known. In the heterotrophs, sugar fermentation
      is achieved by a novel glycolytic pathway involving unusual ADP-dependent kinases
      and ATP synthetases, and novel oxidoreductases that are ferredoxin- rather than
      NAD(P)-linked. Similarly, peptide fermentation involves several unusual
      ferredoxin-linked oxidoreductases not found in mesophilic organisms. Several of
      these oxido-reductases contain tungsten, an element that is rarely used in
      biological systems. Tungsten is present in exceedingly low concentrations in
      normal sea water, but hydrothermal systems contain much higher tungsten
      concentrations, more than sufficient to support hyperthermophilic life.

PMID- 21182700
TI  - Continuous culture as a tool for investigating the growth physiology of
      heterotrophic hyperthermophiles and extreme thermoacidophiles.
AB  - Although there is great scientific and technological interest in examining the
      physiology and bioenergetics of microorganisms from extreme environments,
      difficulties encountered in their cultivation and lack of genetic systems hampers
      the investigation of these issues. As such, we have adapted methods for
      continuous cultivation of mesophilic organisms to extremes of temperature and pH
      to study extremophiles. Since the risk for contamination of extremophilic
      continuous cultures is relatively small, long-term, steady state experiments
      investigating physiological response to culture perturbations are possible.
      Experiments along these lines have provided insights into the significance of
      specific enzymes in the metabolism of particular substrates, in addition to
      providing a better understanding of stress response and unusual physiological
      characteristics of hyperthermophilic and extremely thermoacidophilic
      microorganisms. Several examples are provided here, including the thermal stress
      response of Metallosphaera sedula (T(opt) 74  degrees C) growing at pH 2.0, and
      the response of the heterotrophic hyperthermophiles Pyrococcus furiosus (T(opt)
      98  degrees C), Thermococcus litoralis (T(opt) 88  degrees C) and T. maritima
      (T(opt) 80  degrees C) to changes in growth medium. Also discussed will be how
      the same experimental systems have been used to study exopolysaccharide
      production and biofilm formation by hyperthermophilic heterotrophs and
      facilitated the estimation of bioenergetic parameters for these organisms under a
      variety of growth conditions. Continuous culture, used in conjunction with genome
      sequence information, two-dimensional gel electrophoresis and differential gene
      expression, can provide important insights into the metabolism of high
      temperature extremophiles.

PMID- 21182701
TI  - Bioremediation of phenol by alkaliphilic bacteria isolated from alkaline lake of
      Lonar, India.
AB  - Phenol is an industrially important compound which has a wide range of
      applications. Being highly soluble in water, it appears as the major pollutant in
      waste waters arising from both phenol manufacturing and from industrial units
      that utilise phenol. Because of its toxicity, bioremediation of phenol is
      necessary. Since some of the phenol-bearing industrial waste waters are alkaline
      in nature, use of alkaliphilic bacteria for bioremediation of phenol was
      investigated. Alkaliphilic bacteria were isolated from sediments of an alkaline
      lake in Lonar, Dist. Buldhana, Maharashtra State, India, by phenol enrichment at
      pH 10.0 and phenol concentration of 500 mg/l. The lake (lat. 19 degrees 58'45",
      long. 76 degrees 34') is known to be a unique inland saline lake in Asia. It has
      a circular periphery and diameter of 2 km around the top of the banks and 1.2 km
      at the bottom. The lake has a high saline level (~ 2649 mg/l sodium chloride) and
      a high level of alkalinity (~ 2605 mg/l calcium carbonate). Alkaliphilic strains
      of Arthrobacter spp., Bacillus cereus, Citrobacter freundii, Micrococcus agilis
      and Pseudomonas putida biovar B were capable of removing phenol from waste waters
      arising from industries manufacturing methyl violet (using phenol as one of the
      major raw materials) and cumene-phenol. The waste waters from both these units
      were alkaline in nature (pH ~ 9.95-10.1) and had a high phenol content (368-660
      mg/l). The alkaliphilic bacteria being studied removed 100% of the phenol from
      the industrial waste waters within 48 h of incubation under shake culture
      conditions and at an ambient temperature of 28 +/- 2  degrees C. Bioremediation
      of phenol by alkaliphilic strains of Arthrobacter spp., B. cereus, C. freundii
      and M. agilis seems to be the first report.

PMID- 21182702
TI  - Global microbial ecology: biogeography and diversity of Vibrios as a model.
AB  - An environmental source of cholera was hypothesized as early as the late
      nineteenth century by Robert Koch, but not proven because of the ability of
      Vibrio cholera, the causative agent of cholera, to enter a dormant phase between
      epidemics. Standard bacteriological procedures for isolation of the vibrios from
      the environmental samples, including water, between epidemics generally were
      unsuccessful. Vibrio cholera, a marine vibrio requiring salt for growth, enters
      into a dormant 'viable but non-culturable' stage when conditions are unfavourable
      for growth and reproduction. The association of V. cholera with plankton, notably
      copepods, provides evidence for the environmental origin of cholera, as well as
      an explanation for the sporadic and erratic nature of cholera epidemics. Thus,
      the association of V. cholera with plankton was established only recently,
      allowing analysis of epidemic patterns of cholera, especially in those countries
      where cholera is endemic. The sporadic and erratic nature of cholera epidemics
      can now be related to climate and climate events, such as El Nino. Since
      zooplankton have been shown to harbour the bacterium and zooplankton blooms
      follow phytoplankton blooms, remote sensing can be employed to determine the
      relationship of cases of cholera with chlorophyll, as well as sea surface
      temperature (SST), ocean height, and turbidity. Cholera occurs seasonally in
      Bangladesh with two annual peaks in the number of cases occurring each year. From
      the data obtained and analysed to date, when the height of the ocean is high and
      sea surface temperature is also elevated, cholera cases are numerous. When the
      height is low and sea surface temperature is also low, little or no cholera is
      recorded. From the examination of data for the 1992-1993 cholera epidemic in
      India, preliminary comparisons of cholera data for Calcutta show a similar
      relationship between cholera cases, ocean height and SST. In conclusion, from
      results of studies of SST, phytoplankton and zooplankton, and their relationships
      to incidence of cholera, correlation of selected climatological factors and
      incidence of V. cholera appears to be significant, bringing the potential of
      predicting conditions conducive to cholera outbreaks closer to reality.

PMID- 21182703
TI  - Effects of gilvin on the composition and dynamics of metalimnetic communities of
      phototrophic bacteria in freshwater North-American lakes.
AB  - The spectral distribution of light reaching the populations of phototrophic
      bacteria in the metalimnion of stratified lakes is a selective factor determining
      the community composition. At deep metalimnia, light spectra are enriched in
      photons of the central part of the spectrum (500-600 nm) and benefit
      Chromatiaceae, brown-coloured Chlorobiaceae and phyco-erythrine-containing
      cyanobacteria. Their carotenoids (okenone, spiriloxanthine, isorenieratene) and
      phycoerythrines allow these phototrophic bacteria to use light from the narrow
      central spectral wavebands. Otherwise, shallow metalimnetic communities receive
      light from a wide range (400-800 nm) and their composition is more diverse and
      usually enriched in green-coloured Chlorobiaceae, which are unable to take
      advantage of the central part of the spectrum. Gilvin compounds (humic substances
      dissolved in water), have strong effects on light absorption, especially at
      shorter wavelengths. Therefore, light spectra in lakes with high gilvin contents
      are enriched in photons of long wavelengths (> 600 nm). Several Wisconsin lakes
      with different gilvin contents were studied during the period of summer
      stratification in 1994. Spectral distribution of light reaching their metalimnia
      changed with increasing gilvin contents (measured as g(440) ). In the latter,
      phototrophic metalimnetic bacterial communities were absolutely dominated by
      green-coloured Chlorobiaceae. Intermediate lakes could experiment changes on
      their community composition depending on variations in gilvin content, as
      happened in Little Long lake. The dynamics of this lake was studied during summer
      1995. The ratio of green-coloured species in respect to brown-coloured species
      increased after a sudden increase of gilvin due to strong rainfall. These results
      agree with the photosynthetic advantage of green-coloured Chlorobiaceae under red
      light illumination, inferred from laboratory experiments, and suggest a
      bacteriochlorophyll-dependent, light-harvesting strategy of these phototrophic
      sulphur bacteria.

PMID- 21182704
TI  - Bacterial interactions in the rhizosphere of seagrass communities in shallow
      coastal lagoons.
AB  - Rooted phanerogam communities in the shallow intertidal and subtidal coastal zone
      represent productive and healthy ecosystems. Inorganic nutrients are assimilated
      into seagrass biomass. Much of the organic matter resulting from moribund
      seagrass is rapidly mineralized, principally by bacteria. The microbial community
      of the rhizosphere is also highly active due to the supply of organic matter
      released during photosynthesis. This active sediment community plays an important
      role through carbon, nitrogen and phosphorous cycling in maintaining the
      stability and productivity of seagrass meadows. Over the last two decades,
      however, seagrass meadows in European coastal areas have declined due to
      increasing pollution. As eutrophication advances a trasition occurs from rooted
      phanerogram dominated communities to planktonic algal blooms and/or
      cyanobacterial blooms. Such changes represent the decline of a stable, high
      biodiversity habitat to an unstable one dominated by a few species. These changes
      of community structure can occur rapidly once the internal nutrient and organic
      matter control cycles are exceeded. A field investigation was undertaken to
      establish the spatial distribution of bacterial populations of Zostera noltii
      colonized and uncolonized sediment in the Bassin d'Arcachon, France. Bacteria
      were enumerated using both plate count and MPN techniques for different
      functional groups as well as determining the total bacterial populations present.
      Nitrogen fixation, ammonification, sulphate reduction rates, as well as alkaline
      phosphatase activity were also determined. Colonization of the Z. noltii roots
      and rhizomes was studied by light and scanning electron microscopy. Results
      confirmed that higher bacterial populations were present in the rhizosphere of Z.
      noltii compared to uncolonized sediments. Furthermore, electron microscopy
      identified the rhizome as the main site of colonization for a diverse range of
      morphological groups of bacteria. Sulphate reducing bacteria were identified as
      the key group of bacteria involved in N-fixation in the rhizosphere of Z. noltii.
      The data will be discussed in relation to the role played by the rhizosphere
      microflora in supplying and mobilising nutrients in Z. noltii.

PMID- 21182705
TI  - Carbon load in aquatic ecosystems affects the diversity and biomass of water
      biofilm consortia and the persistence of the pathogen Campylobacter jejuni within
      them.
AB  - The influence of carbon load on autochthonous water microflora population
      distribution and diversity, and on the persistence of Campylobacter jejuni, was
      examined with a two-stage aquatic biofilm model. Serine was chosen since it is a
      carbon source utilised by C. jejuni and concentrations were chosen to reflect
      upper limits of amino acid load reported in surface water. The total viable count
      of the autochthonous biofilm microflora increased with increasing serine
      concentration (10-fold and 20-fold with 5 nM and 5 MUM serine, respectively), as
      did the counts of the microflora in the planktonic phase. Differences in biofilm
      species distribution as determined by culture were small with changes in
      temperature or the addition of serine; but was markedly affected by serine as
      determined by light microscopy, becoming more luxuriant and dominated by long
      filamentous cells. The addition of serine to the water significantly and
      progressively reduced the persistence of C. jejuni, which decreased by 25% and
      50% with serine concentrations of 5 nM and 5 MUM respectively. We have
      demonstrated that carbon load affects the species diversity and density of both
      the planktonic and biofilm phase of aquatic autochthonous microflora. Although
      the survival of C. jejuni in water in a culturable form was sufficient for this
      to be an important vehicle for its transmission, carbon load significantly
      influenced survival; an increase in serine concentration significantly reduced
      survival.

PMID- 21182706
TI  - Campylobacter epidemiology: an aquatic perspective.
AB  - Members of the genus Campylobacter have established themselves as the most common
      human gastro-enteric pathogens throughout much of the developed world. The
      ubiquitous distribution of Campylobacter spp. in animal reservoirs and food
      products derived thereof make such vehicles primary risk factors in contracting
      campylobacteriosis. The contamination rates, identification of common pathogenic
      serotypes and extended survival of Campylobacter in surface waters illustrates
      the potential, but yet to be quantified, campylobacteriosis risk associated with
      untreated water. The existence and potential pathogenicity of viable but
      nonculturable forms of Campylobacter remains a contentious subject. Furthermore,
      the role of such forms in the epidemiology of Campylobacter related disease and
      their involvement in the large number of waterborne gastroenteritis outbreaks
      from which a disease agent cannot be isolated remains to be fully clarified. This
      article presents a survey of current perspectives with regard to the survival and
      epidemiology of Campylobacter spp. in natural water systems.

PMID- 21182707
TI  - The effect of GAC filtration on bacterial regrowth and nitrification in a
      simulated water main.
AB  - A 16-month pilot study in two similar 1200 m water mains was conducted to
      determine the effects of granular activated carbon (GAC) filtration on drinking
      water quality in a distribution system. The results demonstrated that despite the
      higher initial disinfectant residue, the increase in bacteria in the
      conventionally treated and postozonated water was higher than in the water
      additionally treated with GAC filtration and u.v.-disinfection. Accordingly, a
      significant decline in assimilable organic carbon in the postozonated water was
      observed throughout the main, whereas in the GAC-filtered water this decline was
      shifted to the GAC filters. In the GAC-filtered water the conversion of ammonia
      to nitrite and nitrite to nitrate was more intense than in postozonated water.
      The findings confirm that GAC filtration increases the biological stability of
      drinking water even when treating cold humic waters in which biodegradation is
      generally limited by phosphorus. However, it appears that biological treatment
      favours the slow kinetics of nitrifying bacteria, thus allowing nitrification to
      occur even under cold water conditions in a distribution system.

PMID- 21182708
TI  - Cyanobacteria as agents for the control of pollution by pesticides and
      chlorinated organic compounds.
AB  - Cyanobacteria are phototrophic aquatic micro-organisms that are found in a
      variety of environments, including polluted ones. Fifteen strains of
      cyanobacteria that belong to three taxonomic groups are able to degrade lindane
      (lambda-hexachlorocyclohexane, a recalcitrant pesticide). The initial degradation
      pathway has been studied in two filamentous nitrogen-fixing strains of Anabaena
      sp. PCC 7120 and Nostoc ellipsosporum. These cyanobacteria dechlorinated loindane
      first to pentachlorocyclohexene and then to a mixture of trichlorobenzenes, and
      possibly further. Lindane dechlorination by these organisms occurred only in the
      presence of nitrate in the medium. Both ammonium and darkness inhibited the
      process. This combination of observations led us to the hypothesis that the
      nitrate-reduction system of cyanobacteria may be involved in dechlorination. The
      hypothesis was proven by the analysis of Anabaena sp. transpositional mutants in
      four genes of the nir operon. The mutants were unable to dechlorinate lindane.
      However, there was no correlation between lindane dechlorination and activities
      of individual proteins encoded by this operon. Genetic engineering of Anabaena
      sp. and N. ellipsosporum that introduced linA lindane dechlorination operon from
      Psuedomonas paucimobilis allowed us to uncouple dechlorination from nitrate
      requirement. Introduction, by genetic engineering, of fcABC (the 4-chlorobenzoate
      dechlorination system from Arthrobacter globiformis) to Anabaena sp and N.
      ellipsosporum rendered these strains newly capable of 4-chlorobenzoate
      dechlorination both constitutively and inducible by an environmental factor.

PMID- 21182709
TI  - Rapid direct methods for enumeration of specific, active bacteria in water and
      biofilms.
AB  - Conventional methods for detecting indicator and pathogenic bacteria in water may
      underestimate the actual population due to sublethal environmental injury,
      inability of the target bacteria to take up nutrients and other physiological
      factors which reduce bacterial culturability. Rapid and direct methods are needed
      to more accurately detect and enumerate active bacteria. Such a methodological
      advance would provide greater sensitivity in assessing the microbiological safety
      of water and food. The principle goal of this presentation is to describe novel
      approaches we have formulated for the rapid and simultaneous detection of
      bacteria plus the determination of their physiological activity in water and
      other environmental samples. The present version of our method involves the
      concentration of organisms by membrane filtration or immunomagnetic separation
      and combines an intracellular fluorochrome (CTC) for assessment of respiratory
      activity plus fluorescent-labelled antibody detection of specific bacteria. This
      approach has also been successfully used to demonstrate spatial and temporal
      heterogeneities of physiological activities in biofilms when coupled with
      cryosectioning. Candidate physiological stains include those capable of
      determining respiratory activity, membrane potential, membrane integrity, growth
      rate and cellular enzymatic activities. Results obtained thus far indicate that
      immunomagnetic separation can provide a high degree of sensitivity in the
      recovery of seeded target bacteria (Escherichia coli O157:H7) in water and
      hamburger. The captured and stained target bacteria are then enumerated by either
      conventional fluorescence microscopy or ChemScan(R), a new instrument that is
      very sensitive and rapid. The ChemScan(R) laser scanning instrument (Chemunex,
      Paris, France) provides the detection of individual fluorescently labelled
      bacterial cells using three emission channels in less than 5 min. A high degree
      of correlation has been demonstrated between results obtained with the ChemScan
      and traditional plate counts of mixed natural bacterial populations in water. The
      continuing evolution of these methods will be valuable in the rapid and accurate
      analysis of environmental samples.

PMID- 21182710
TI  - Dielectrophoretic analysis of microbes in water.
AB  - Traditional microbiological methods are still used extensively for analysis of
      micro-organisms in water. However, they are inefficient due to a high labour
      input requirement, a low sample capacity, and often a long time lag before
      results are available. Analytical stages involving incubation and growth
      (enrichments and colony isolation) contribute the greatest delay in reporting,
      although subsequent identification can also be protracted. The use of
      electrometric growth analysers (measuring impedance, conductance or capacitance
      changes) is now more common in water microbiology. Although these instruments can
      provide more rapid results and provide increased handling capacity, the bacterial
      generation times required to provide detectable changes cause delays and suitable
      selective media are not fully developed for all microbes of interest. Most other
      recent methods have equally disappointing drawbacks and thus extensive research
      continues in order to realise the ambition of 'real-time' analytical
      microbiology. Several research groups have demonstrated the potential of
      dielectrophoresis in providing microbial concentration, separation and
      identification systems which are not limited by bacterial growth and are
      therefore extremely rapid. Dielectrophoresis occurs when cells are placed in non
      uniform electric fields. The cells move towards the electrodes (regardless of the
      direction of the applied field) as determined by their dielectric properties
      (conductivity and permittivity) rather than by their charge as occurs in
      electrophoresis. Also, the polarisability of the cells, and therefore the
      polarity and magnitude of the dielectrophoretic force, varies as a function of
      the electric field frequency. Because the dielectric properties of a particular
      cell type have characteristic frequency-dependent components, if cell collection
      at electrodes is observed across a frequency range, the collection spectrum
      produced is distinctive for the cell type under investigation. This can be
      exploited for analytical and separation applications in microbiology. This paper
      will describe rapid analytical techniques based on electrokinetic phenomena under
      research and development at York. These include dielectrophoretic enrichment,
      concentration and characterisation systems for the analysis of water bacteria and
      protozoa.

PMID- 21182711
TI  - Methods for the determination of filamentous fungi in treated and untreated
      waters.
AB  - Results of two recent projects in the UK and USA have shown that many species of
      filamentous fungi are present in both untreated and treated waters. Samples have
      been taken from surface waters and from a range of points within distribution
      networks. Isolation programmes employing a range of methods and media, combined
      with expert taxonomic study have yielded extensive lists of waterborne fungi
      identified, where possible, to species level: 141 different taxa from the UK and
      140 from the USA. In the UK study an average of 32 different fungal taxa were
      isolated from each surface water and compared to nine from each treated tap
      water. Certain fungi appear more frequently than others, in particular species of
      Aspergillus, Cladosporium, Epicoccum, Penicillium and Trichoderma appear to be
      very common but species from many other genera are also present. The significance
      of fungi in water systems is poorly understood, many of the species isolated from
      water are known to be capable of producing toxic secondary metabolites, are
      involved in food spoilage, or are plant pathogens; some are even opportunistic
      human pathogens. Direct observation of isolation filters has shown that fungi are
      present equally as spores and as hyphae. Studies have shown that fungi are
      capable of growth in both treated and untreated water. While traditional methods
      of measurement such as dry weight are inadequate for determining growth in water,
      analysis of ergosterol-a universal component of cell membranes amongst
      filamentous fungi-has provided a very sensitive means of measuring fungal growth
      in water to levels of < 1 MUg(-1) and may prove to be a suitable method for
      detecting general fungal levels in water samples.

PMID- 21182712
TI  - Conventional culture for water quality assessment: is there a future?
AB  - Conventional culture for the detection, enumeration and identification of micro
      organisms has been the traditional tool of the microbiologist. It is, however,
      time-consuming and labour-intensive and confirmed results often require several
      days of analysis. Culture may not grow the organisms being sought and for
      enumeration may only detect a small proportion of the total population. However,
      it does have the advantage of being simple to use and relatively inexpensive. It
      is also a direct means of assessing cell viability. Novel fluorogenic dyes and
      fluorgenic and chromogenic substrates have overcome some of these problems by
      providing a means of rapid and specific detection and enumeration whilst removing
      the need for subculture and confirmation tests. Immunological tests such as ELISA
      have significantly reduced analysis time by providing specific target organism
      detection. Molecular techniques have removed the need for culture. Improvements
      in sensitivity, and removal of the inhibitory nature of sample matrices, have
      allowed analysts to detect low levels of micro-organisms but the questions of
      viability and comparability with cultural techniques still remain. Are we about
      to see a change of culture in water quality assessment, or can cultural
      techniques be developed that reduce analysis time to a few hours and can rapid
      methods be used for detecting the presence and viability of organisms?

PMID- 21182713
TI  - The effects of pollution on fish health.
AB  - Potentially harmful substances-e.g. pesticides, heavy metals and hydrocarbons-are
      often released into the aquatic environment. When large quantities of pollutants
      are released there may be an immediate impact as measured by large-scale sudden
      mortalities of aquatic organisms, e.g. fish kills resulting from contamination of
      waterways with agricultural pesticides. Lower levels of discharge may result in
      an accumulation of the pollutants in aquatic organisms. The end results, which
      may occur long after the pollutants have passed through the environment, include
      immunosuppression, reduced metabolism, and damage to gills and epithelia.
      However, the link between adverse water quality and fish diseases is not proven.
      Alleged pollution-related diseases include epidermal papilloma, fin/tail rot,
      gill disease, hyperplasia, liver damage, neoplasia and ulceration. Many surveys
      have indicated a greater proportion of diseased fish in polluted compared to non
      polluted marine sites. Yet, the value of such surveys may be questioned. Specific
      examples of fish diseases thought to reflect the effects of pollution include
      surface lesions attributed to Serratia plymuthica, fin and tail rot caused by
      Aeromonas hydrophila and Pseudomonas fluorescens, gill disease resulting from the
      actvity of Flavobacterium spp., vibriosis as caused by Vibrio anguillarum, and
      enteric redmouth (causal agent, Yersinia ruckeri). Research indicated that some
      of the diseases caused by Aeromonas, Flavobacterium and Pseudomonas resulted from
      generally adverse water quality, i.e. higher than usual quantities of organic
      material, oxygen depletion, changes in pH values and enhanced microbial
      populations. Some infections with Serratia and Yersina may well have reflected
      contamination of waterways with domestic sewage, e.g. leaking septic tanks. At
      least one outbreak of vibriosis was linked to high concentrations of copper,
      which may have debilitated the fish making them more susceptible to disease.

PMID- 21182714
TI  - Bacteriocin activity and probiotic activity of Aeromonas media.
AB  - Three strains of Aeromonas media (161, A164 and A199) were shown to be active in
      vitro producers of bacteriocin-like inhibitory substances (BLIS). For example,
      the producer strain, Aer. media A199, displayed antagonistic activity against all
      strains tested of Aer. caviae, Aer. hydrophila, Aer. salmonicida, Aer. veronii
      var. sobria, Listonella anguillarum, Photobacterium damsella, eight species of
      Vibrio and Yersinia ruckeri. Because of this wide-ranging activity against
      fish/shellfish pathogens, A199 was chosen for the probiotic work. By contrast,
      however, the BLIS produced by A199 did not inhibit the growth of Enterococcus
      seriolicida. The aim of the project was to ascertain whether or not the activity
      observed in vitro could be repeated in vivo. The ability of BLIS-producing strain
      A199 to act as a probiotic was assessed on the host animal, Crassostrea gigas, by
      testing whether or not strain A199 could prevent death of the oyster larvae when
      challenged with V. tubiashit. Whereas larvae, challenged with the Vibrio, died
      within 5 days, the presence of both the pathogen and the probiotic strain,
      together, did not affect the viability of the larvae over the same time period;
      the viability of larvae challenged with A199 alone was also unaffected when
      compared with the viability of unchallenged larvae (controls). These findings
      have important, economic implications for those engaged in the oyster producing
      industry where heavy losses can be experienced as a result of an infectious
      outbreak. At this stage, the association between BLIS activity and probiotic
      activity is circumstantial and, hence, future work will involve the use of non
      BLIS-producing strains of Aer. media and BLIS-negative variants of the producer.
      Moreover, extension of the project will involve the use of other BLIS-producing
      strains (A161, and A164), hosts (salmon, crayfish, scallops and abalone) and
      pathogens.

PMID- 21182715
TI  - Food safety and products from aquaculture.
AB  - Aquaculture is currently one of the fastest growing food production systems in
      the world with production increasing at an average rate of 9.6% per year over the
      past decade. As world fish stocks are reaching the limits of exploitation, we
      shall rely to a far greater extent on products from aquaculture as food sources
      of high nutritional value. Approximately 90% of global aquaculture production is
      based in Asia, where it provides an important source of dietary animal protein of
      the region and income for millions of small-scale farmers. Commercial aquaculture
      contributes significantly to the economies of many producing countries, where
      highly valued species are a major source of foreign. Many different aquaculture
      systems exist world wide, ranging from small family-sized fish ponds to intensive
      cage culture industries as used in salmon fishing. There has been an expansion in
      the use of integrated farming systems, especially in Asia, where animal and human
      faeces are used to fertilise ponds. This paper will review global aquaculture
      systems used in the production of finfish and crustaceans and will focus on
      potential hazards arising from biological contamination of products that pose
      risks to public health.

PMID- 21182717
TI  - Just another stoma - why have we not improved?

PMID- 21182720
TI  - Topical KINOSTATTM ameliorates the clinical development and progression of
      cataracts in dogs with diabetes mellitus.
AB  - OBJECTIVE: To determine whether topical administration of the aldose reductase
      inhibitor KinostatTM can ameliorate the onset or progression of cataracts in dogs
      with naturally occurring diabetes mellitus (DM). MATERIALS AND METHODS: A
      randomized, prospective, double-masked placebo control pilot study was conducted
      with 40 dogs newly diagnosed with DM with no or minimal lens changes. Twenty
      eight dogs received KinostatTM and 12 dogs received placebo. PROCEDURES: Owners
      administered the agent into both eyes three times daily for 1 year and compliance
      was monitored with log sheets. Complete ophthalmic examinations were performed on
      dilated eyes at the time of enrollment and 1, 2, 3, 6, and 12 months into
      treatment. Cataract severity was assessed on a scale of 0-3. At 12 months, full
      bloodwork, including HbA1C and blood KinostatTM levels were performed. RESULTS:
      After 12 months of treatment, the cataract score in the placebo group
      significantly increased with seven dogs (14 eyes) developing mature cataracts,
      two dogs (4 eyes) developing cortical opacities, and one dog (2 eyes) developing
      equatorial vacuoles with mild punctate cortical opacities. In contrast, the
      cataract score in the KinostatTM treated dogs was significantly less with seven
      developing anterior equatorial vacuoles, two developing incipient anterior
      cortical cataracts, and four developing mature cataracts. In fact, the cataract
      scores of the KinostatTM group at 12 months did not significantly increase from
      the score at the time of enrollment. The HbA1C values between the two groups
      after 12 months of treatment were similar, and no blood levels of KinostatTM were
      found in any enrolled dog. CONCLUSION: The onset and/or progression of cataracts
      in dogs with DM can be significantly delayed by topical administration of
      KinostatTM.

PMID- 21182721
TI  - Cellular-resolution in vivo imaging of the feline retina using adaptive optics:
      preliminary results.
AB  - PURPOSE: To perform cellular-level in vivo imaging of the feline retina using an
      adaptive optics flood illumination fundus camera (AO FIFC) designed for the human
      eye. MATERIALS AND METHODS: Cellular-level images were obtained from three eyes
      of two normal sedated cats. Ocular aberrations were corrected using an AO system
      based on a 52-acuator electromagnetic deformable mirror and a 1024 lenslet
      Hartmann-Shack sensor (both Imagine Eyes, Orsay, France). A square 3 degrees *3
      degrees  area of the ocular fundus was flood-illuminated by a pulsed LED emitting
      at 850 nm and imaged onto a low-noise, high-resolution CCD camera. The animal's
      pupils were dilated and the effective pupil size was set to 7.5 mm. Conjunctival
      atraumatic clips were used to avoid eyeball movements and eyelid closure. The
      cornea was artificially hydrated throughout the experiments. Each acquisition
      consisted of 20 consecutive images, out of which 10 were numerically averaged to
      produce an enhanced final image. RESULTS: The total amount of ocular aberrations
      was greatly reduced by the AO correction, from 2.4 to 0.21 microns root mean
      square on average. The resulting images presented white dots distributed at a
      density similar to that of cone photoreceptors and they allowed us to visualize
      small blood vessels and nerve fiber bundles at a higher resolution than
      classically obtained with conventional fundus photography. CONCLUSION: Retinal
      imaging with cellular resolution was feasible in cats under sedation using an AO
      FIFC designed for human eyes without any optical modification. The AO FIFC
      technology could find new applications in clinical, pharmacological, and
      toxicological investigations.

PMID- 21182722
TI  - Transfrontal orbitotomy in the dog: an adaptable three-step approach to the
      orbit.
AB  - PURPOSE: To describe an adaptable and extensive method for orbitotomy in the dog.
      METHODS: An adaptable three-step technique for orbitotomy was developed and
      applied in nine consecutive cases. The steps are zygomatic arch resection
      laterally, temporalis muscle elevation medially and zygomatic process osteotomy
      anteriorly-dorsally. The entire orbit is accessed with excellent exposure and
      room for surgical manipulation. Facial nerve, lacrimal nerve and lacrimal gland
      function are preserved. The procedure can easily be converted into an orbital
      exenteration. RESULTS: Exposure of the orbit was excellent in all cases and
      anatomically correct closure was achieved. Signs of postoperative discomfort were
      limited, with moderate, reversible swelling in two cases and mild in seven. Wound
      infection or emphysema did not occur, nor did any other complication attributable
      to the operative procedure. Blinking ability and lacrimal function were preserved
      over follow-up times ranging from 1 to 4 years. CONCLUSIONS: Transfrontal
      orbitotomy in the dog offers excellent exposure and room for manipulation.
      Anatomically correct closure is easily accomplished, postoperative discomfort is
      limited and complications are mild and temporary.

PMID- 21182723
TI  - Rabbits' eye globe sonographic biometry.
AB  - OBJECTIVE: To measure intraocular structures in New Zealand White breed rabbits
      (Oryctolagus cuniculus Linnaeus, 1758) using A-mode and B-mode ultrasound with a
      20 MHz transducer. PROCEDURES: In this study, the eyes of 15 rabbits were
      evaluated for determination of intraocular measurements using an ophthalmic
      ultrasound unit able to operate in both A and B-modes. The distances from the
      cornea to the anterior capsule of the lens (D1), from the anterior capsule of the
      lens to the posterior capsule of the lens (D2), from the posterior capsule of the
      lens to the retina (D3) and the complete length of the eye, which corresponds to
      the distance from the cornea to the retina (D4) were taken. RESULTS: The mean
      values obtained were 2.70 mm (+/- 0.22 mm) for D1, 7.32 mm (+/- 0.40 mm) for D2,
      7.10 mm (+/- 0.45 mm) for D3 and 17.12 mm (+/- 0.41 mm) for D4. Statistical
      analyses using the Student's t-test showed that there were no differences between
      the eyes. CONCLUSIONS: The study was feasible without the need of pharmacological
      restraint and yielded normal mean values for ocular sonographic biometry in
      rabbits.

PMID- 21182724
TI  - Anterior uveal spindle cell tumor in a cat.
AB  - PURPOSE: To describe a case of anterior uveal spindle cell tumor in a cat with
      features similar to spindle cell tumor of blue eyed dogs. METHODS: A 10-year-old
      female spayed domestic short-haired cat was referred for an iris mass OS. The
      mass was solitary, nodular, nonpigmented, located medially, and causing dyscoria.
      A diagnosis of a benign epithelial tumor was suggested by a FNA of the mass. The
      cat was lost to follow-up for 2 years, after which time she re-presented with
      glaucoma, blindness and grossly evident iridal mass enlargement OS.
      Transconjunctival enucleation was performed and the globe submitted for
      histopathology. RESULTS: Histopathology of the enucleated globe revealed the
      superior iris to be infiltrated and effaced by a large population of neoplastic
      spindle cells. The cells were arranged in streams and bundles and exhibited
      Antoni-A and Antoni-B tissue patterns, which are characteristic of Schwann cell
      tumors. Mitotic figures were rare and cellular pleomorphism moderate.
      Immunohistochemical staining was positive for S-100 protein and glial fibrillary
      acidic protein (GFAP), and negative for Melan-A. Interestingly, there was no
      histological evidence of glaucoma. CONCLUSIONS: Based on its histopathologic
      characteristics, this iris tumor was diagnosed as a Schwann cell variant of a
      peripheral nerve sheath tumor (PNST) closely resembling the spindle cell tumor of
      blue-eyed dogs. Anterior uveal PNST has not been previously reported in cats to
      the authors' knowledge. The presence of Antoni type A and type B tissue patterns
      along with immunohistochemical staining may facilitate a diagnosis of PNST and
      rule out malignant melanoma.

PMID- 21182725
TI  - Unusual presentation of a metastatic uveal melanoma in a cat.
AB  - A 10 year-old, spayed female Domestic Short-Haired (DSH) cat was diagnosed with a
      large primary uveal melanoma and exenteration was recommended. Thoracic
      radiographs, abdominal ultrasonography, and complete blood count and serum
      biochemistry panel did not reveal any abnormality compatible with metastatic
      disease and surgery was performed. Histopathologic study of the eye confirmed a
      diffuse iris melanoma. Five months later, the cat presented with a lameness of
      the right anterior extremity. On physical exam the right elbow was swollen and
      painful. Radiographs showed a severe osteolysis of the radial head and proximal
      diaphysis. Fine needle aspiration of the radius head identified a round cell
      neoplasm with scattered cells containing intracytoplasmatic pigmented granules,
      compatible with metastatic melanoma. The owners decided not to treat the patient
      with chemotherapy and declined a biopsy. Two months later, the cat died and
      necropsy was performed confirming bone metastasis of the uveal melanoma. A
      diagnosis of generalized metastasis from primary diffuse iris melanoma was made.
      This report describes, for the first time, long bone metastasis from an uveal
      melanoma in a cat.

PMID- 21182726
TI  - Advancements in ocular drug delivery.
AB  - This review covers both noninvasive and invasive ophthalmic drug delivery systems
      that can have application to therapy of veterinary ophthalmic diseases.
      Noninvasive approaches include gel technologies, permeation enhancement via pro
      drug development, solubilization agents and nanoparticle technologies,
      iontophoresis, microneedles, drug-eluting contact lenses and eye misters, and
      microdroplets. More invasive systems include both eroding implants and noneroding
      technologies that encompass diffusion based systems, active pumps, intraocular
      lenses, suprachoroidal drug delivery, and episcleral reservoirs. In addition to
      addressing the physiologic challenges of achieving the necessary duration of
      delivery, tissue targeting and patient compliance, the commercial development
      factors of biocompatibility, sterilization, manufacturability and long-term
      stability will be discussed.

PMID- 21182728
TI  - M, M, M & M: a mnemonic for assessing obesity.
AB  - Obese individuals can present with a wide range of medical and psychosocial
      problems, which can promote weight gain, provide important indications for
      treatment but, in some cases, also pose significant barriers to management. To
      ensure a complete assessment and consideration of these factors, I propose the
      use of a simple mnemonic consisting of four Ms or 'M, M, M, & M' that stand for
      Mental, Mechanical, Metabolic and Monetory, respectively, and may help the busy
      practitioner navigate through a thorough assessment of clients presenting with
      excess weight.

PMID- 21182731
TI  - [Apropos ... Microscopically controlled surgery].

PMID- 21182735
TI  - Medicinal leeches for the treatment of venous congestion and hematoma after
      plastic reconstructive surgery.
AB  - BACKGROUND: Leeches were used for medical purposes as long as 2 000 years ago in
      ancient Egypt. In recent years the use of medicinal leeches became rather popular
      again, e. g. to improve blood circulation in ischemic tissue after reconstructive
      plastic surgery. PATIENTS AND METHODS: In a single center, retrospective study 23
      consecutive cases were analyzed in which medicinal leeches had been used
      therapeutically after plastic reconstructive surgery. All cases were categorized
      regarding the indication for leech therapy, the onset, the duration, the number
      of leeches and the number of sessions. RESULTS: Among the group of patients there
      were 7 female and 16 male patients with a mean age of 73 +/- 14 years (48-94
      years) altogether. The main indications were venous congestion (12/23; 52 %) and
      hematoma (9/23; 39 %). Two cases were diagnosed with a necrosis of the tip of the
      flap and therefore received leech therapy (2/23; 9 %). The average number of
      leeches was 2.6 leeches/session, the number of sessions was 1.7 +/- 0.8. 20/23
      patients (87 %) showed a restitutio ad integrum after leech therapy, in 3/23
      patients (13 %) a necrosis of the tip of the flap could not be prevented. A
      clinical improvement was noticed after an average of 1.1 +/- 0.3 days.
      CONCLUSIONS: The early application of medicinal leeches can improve local
      hemodynamic conditions. Leech therapy is a simple and effective method; the cost
      efficiency of the treatment is high.

PMID- 21182737
TI  - Diagnostic procedures for venous problems.
AB  - Venous diseases are a common worldwide problem. Numerous methods for the
      evaluation of the venous system are available. The major objectives include the
      diagnosis and medically relevant classification of varicose vein disease, as well
      as the identification and assessment of hemodynamic disturbances. In addition, it
      is necessary to characterize and classify disturbances of the deep venous system
      and to differentiate between primary and secondary varicose veins. The physician
      should also exclude or detect and classify concomitant peripheral arterial
      occlusive disease, and an accompanying disorder of lymphatic drainage. The
      diagnostic evaluation of venous disorders, depending on the severity of the
      disease, includes as standard the use of Doppler sonography. Light reflection
      rheography (LRR), photoplethysmography (PPG), venous occlusion plethysmography
      and phlebodynamometry (PD) complete the hemodynamic evaluation. The standard
      imaging technique now routinely used is duplex color scanning. More complex
      imaging studies include ascending and descending phlebography computed tomography
      or magnetic resonance imaging. In selected cases invasive investigations or
      serological tests may complement the diagnostic work-up.

PMID- 21182739
TI  - [33-year-old woman with nodules on the nipple].

PMID- 21182746
TI  - Abstracts of the 13th Annual Meeting of the European Societies for Sexual
      Medicine (ESSM). Malaga, Spain. November 14-17, 2010.

PMID- 21182747
TI  - IL-1 receptor antagonist gene polymorphism in idiopathic recurrent spontaneous
      abortion in a Chinese Han population.
AB  - Interleukin-1 receptor antagonist (IL-1Ra) has been supposed to play important
      roles in pregnancy. The purpose of this study was to evaluate the association
      between the polymorphisms of IL-1Ra gene (IL1RN) variable number tandem repeat
      (VNTR) in intron 2 with idiopathic recurrent spontaneous abortion (RSA). Ninety
      two RSA patients and hundred normal women with at least one live birth and no
      history of miscarriage were included in the study. Frequencies of the IL1RN
      alleles and genotypes were determined. Data revealed that the prevalence of IL1RN
      allele and genotype was not significant between the RSA and control group (all P
      > 0.05). Our finding indicated that the polymorphism VNTR of IL1RN gene in intron
      2 may not be a risk factor for RSA in the Chinese Han population.

PMID- 21182748
TI  - Sequence of a novel HLA-B*51 allele in a volunteer haematopoietic stem cell
      donor.
AB  - We describe a novel HLA-B*51 allele detected by DNA direct sequencing. The
      sequence of this allele has been officially named B*51:78 as a confirmatory
      sequence. This new allele nucleotide sequence differs from HLA-B*51:01:01 for two
      point mutations in exon 2 where codons 79-80 change from CGG-ATC to CGC-ACC
      (p.Ile80Thr).

PMID- 21182749
TI  - Class II DRB polymorphism and sequence diversity in two vesper bats in the genus
      Myotis.
AB  - Almost no studies have been done with respect to major histocompatibility complex
      (MHC) polymorphism and sequence diversity in bats, although they account for one
      in five living mammalian species. We analysed MHC Class II DRB polymorphism and
      sequence diversity in two Mexican verpertilionid bat species, the widespread
      continental species Myotis velifer and the narrowly distributed (and endangered)
      island endemic Myotis vivesi. We find extensive DRB polymorphism in the
      widespread M. velifer, similar to that commonly reported in other mammals. The
      geographically restricted M. vivesi by contrast shows only very limited
      polymorphism. We conclude that M. vivesi has undergone a dramatic loss of MHC
      polymorphism. The significance of this inference in light of other information on
      population structure and genetic diversity in this species is discussed.

PMID- 21182750
TI  - Genetic variants of the inflammatory C-reactive protein and schizophrenia in
      Armenian population: a pilot study.
AB  - C-reactive protein (CRP) is an inflammation marker implicated in the pathogenesis
      of schizophrenia. To investigate association of the CRP rs1417938, rs1800947,
      rs1205 variants with susceptibility to schizophrenia 208 unrelated Armenians (103
      patients and 105 healthy controls) were genotyped. In this pilot study, none of
      studied variants was associated with schizophrenia.

PMID- 21182752
TI  - Abstracts of the 5th UK Stroke Forum Conference. November 30-December 2, 2010.
      Glasgow, United Kingdom.

PMID- 21182753
TI  - Abstracts of RANZCR (Royal Australian and New Zealand College of Radiologists)
      61st Annual Scientific Meeting. October 14-17, 2010. Perth, Western Australia,
      Australia.

PMID- 21182754
TI  - Development, evaluation and validation of a new instrument for measurement
      quality of life in the parents of children with chronic disease.
AB  - BACKGROUND: Childhood chronic disease may affect patients' and their family's
      functioning. Particularly parents, who play an important role in cooperation
      between patient and health care professionals, report impaired health-related
      quality of life (HRQOL). The aim of this study was development, evaluation and
      validation of a new instrument: Quality of Life in a Child's Chronic Disease
      Questionnaire (QLCCDQ). The questionnaire is addressed to parents of children
      with a chronic disease. METHODS: Study design included semi structured interview
      and qualitative study, which allowed to identify most troublesome problems.
      Following the results the questionnaire was developed, which consists of 15
      questions and covers domains--emotions, patients -perceived symptoms, roles
      limitations. An observational study involving parents of asthma and diabetes
      children was conducted to assess the psychometric characteristics of the measure.
      Psychometric testing was based on the reliability of defined subscales, construct
      validity, reproducibility assessment, as well as comparison between
      stable/unstable disease stages and parents of healthy children. RESULTS: Most
      troublesome concerns for parents of child with chronic disease included emotional
      distress and feeling depressed due to child's disease, avoiding social
      interactions due to child's disease or symptoms. 98 parents of children with
      asthma or insulin - depended diabetes participated in the psychometric testing of
      QLCCDQ. Internal consistency reliability for the defined subscales ranged between
      0.77 and 0.93. Reproducibility based on the weighted kappa coefficients showed
      expected level of agreement and was almost perfect in case of 8 questions,
      substantial for 5 questions and moderate for 2 questions. QLCCDQ demonstrated
      very good construct validity--all subscales showed statistically significant
      correlations ranging from 0.4 to 0.9. QLCCDQ scores differed significantly by
      clinical status--parents of children qualified as stable presented higher scores
      in most subscales in comparison to parents of children with unstable disease.
      CONCLUSIONS: The QLCCDQ shows good internal consistency, test-retest reliability,
      and construct validity. The questionnaire may be useful in helping to understand
      the impact of chronic child's disease on parental perception of health outcomes.

PMID- 21182755
TI  - Intrasexual competition facilitates the evolution of alternative mating
      strategies in a colour polymorphic fish.
AB  - BACKGROUND: Intense competition for access to females can lead to males
      exploiting different components of sexual selection, and result in the evolution
      of alternative mating strategies (AMSs). Males of Poecilia parae, a colour
      polymorphic fish, exhibit five distinct phenotypes: drab-coloured (immaculata),
      striped (parae), structural-coloured (blue) and carotenoid-based red and yellow
      morphs. Previous work indicates that immaculata males employ a sneaker strategy,
      whereas the red and yellow morphs exploit female preferences for carotenoid-based
      colours. Mating strategies favouring the maintenance of the other morphs remain
      to be determined. Here, we report the role of agonistic male-male interactions in
      influencing female mating preferences and male mating success, and in
      facilitating the evolution of AMSs. RESULTS: Our study reveals variation in
      aggressiveness among P. parae morphs during indirect and direct interactions with
      sexually receptive females. Two morphs, parae and yellow, use aggression to
      enhance their mating success (i.e., number of copulations) by 1) directly
      monopolizing access to females, and 2) modifying female preferences after winning
      agonistic encounters. Conversely, we found that the success of the drab-coloured
      immaculata morph, which specializes in a sneak copulation strategy, relies in its
      ability to circumvent both male aggression and female choice when facing all but
      yellow males. CONCLUSIONS: Strong directional selection is expected to deplete
      genetic variation, yet many species show striking genetically-based
      polymorphisms. Most studies evoke frequency dependent selection to explain the
      persistence of such variation. Consistent with a growing body of evidence, our
      findings suggest that a complex form of balancing selection may alternatively
      explain the evolution and maintenance of AMSs in a colour polymorphic fish. In
      particular, this study demonstrates that intrasexual competition results in
      phenotypically distinct males exhibiting clear differences in their levels of
      aggression to exclude potential sexual rivals. By being dominant, the more
      aggressive males are able to circumvent female mating preferences for attractive
      males, whereas another male type incorporates subordinate behaviours that allow
      them to circumvent male aggression and female mating preferences. Together, these
      and previous results indicate that exploiting different aspects of social
      interactions may allow males to evolve distinct mating strategies and thus the
      long term maintenance of polymorphisms within populations.

PMID- 21182757
TI  - Incidence of anogenital warts in Germany: a population-based cohort study.
AB  - BACKGROUND: Human papilloma virus (HPV) types 6 and 11 account for 90 percent of
      anogenital warts (AGW). Assessment of a potential reduction of the incidence of
      AGW following introduction of HPV vaccines requires population-based incidence
      rates. The aim of this study was to estimate incidence rates of AGW in Germany,
      stratified by age, sex, and region. Additionally, the medical practitioner
      (gynaecologist, dermatologist, urologist etc.) who made the initial diagnosis of
      AGW was assessed. METHODS: Retrospective cohort study in a population aged 10 to
      79 years in a population-based healthcare insurance database. The database
      included more than 14 million insurance members from all over Germany during the
      years 2004-2006. A case of AGW was considered incident if a disease-free period
      of twelve months preceded the diagnosis. To assess regional variation, analyses
      were performed by federal state. RESULTS: The estimated incidence rate was
      169.5/100,000 person-years for the German population aged 10 to 79 years. Most
      cases occurred in the 15 to 40 years age group. The incidence rate was higher and
      showed a peak at younger ages in females than in males. The highest incidence
      rates for both sexes were observed in the city-states Berlin, Hamburg and Bremen.
      In females, initial diagnosis of AGW was most frequently made by a gynaecologist
      (71.7%), whereas in males, AGW were most frequently diagnosed by a dermatologist
      (44.8%) or urologist (25.1%). CONCLUSIONS: Incidence of AGW in Germany is
      comparable with findings for other countries. As expected, most cases occurred in
      the younger age groups. The frequency of diagnoses of AGW differs between sexes
      and women and men receive treatment by doctors of different specialties.

PMID- 21182756
TI  - Profiling spermatogenic failure in adult testes bearing Sox9-deficient Sertoli
      cells identifies genes involved in feminization, inflammation and stress.
AB  - BACKGROUND: Sox9 (Sry box containing gene 9) is a DNA-binding transcription
      factor involved in chondrocyte development and sex determination. The protein's
      absence in testicular Sertoli nurse cells has been shown to disrupt testicular
      function in adults but little is known at the genome-wide level about molecular
      events concomitant with testicular break-down. METHODS: To determine the genome
      wide effect on mRNA concentrations triggered by the absence of Sox9 in Sertoli
      cells we analysed adult testicular tissue from wild-type versus mutant mice with
      high-density oligonucleotide microarrays and integrated the output of this
      experiment with regulatory motif predictions and protein-protein network data.
      RESULTS: We report the genome-wide mRNA signature of adult testes lacking Sox9 in
      Sertoli cells before and after the onset of late spermatogenic failure as
      compared to fertile controls. The GeneChip data integrated with evolutionarily
      conserved Sox9 DNA binding motifs and regulatory network data identified genes
      involved in feminization, stress response and inflammation. CONCLUSIONS: Our
      results extend previous observations that genes required for female gonadogenesis
      are up-regulated in the absence of Sox9 in fetal Sertoli cells to the adult
      stage. Importantly, we identify gene networks involved in immunological processes
      and stress response which is reminiscent of a phenomenon occurring in a sub-group
      of infertile men. This suggests mice lacking Sox9 in their Sertoli cells to be a
      potentially useful model for adult human testicular failure.

PMID- 21182758
TI  - Gene expression profiling of subcutaneous adipose tissue in morbid obesity using
      a focused microarray: distinct expression of cell-cycle- and differentiation
      related genes.
AB  - BACKGROUND: Obesity results from an imbalance between food intake and energy
      expenditure, which leads to an excess of adipose tissue. The excess of adipose
      tissue and adipocyte dysfunction associated with obesity are linked to the
      abnormal regulation of adipogenesis. The objective of this study was to analyze
      the expression profile of cell-cycle- and lipid-metabolism-related genes of
      adipose tissue in morbid obesity. METHODS: We used a custom-made focused cDNA
      microarray to determine the adipose tissue mRNA expression profile. Gene
      expression of subcutaneous abdominal fat samples from 15 morbidly obese women was
      compared with subcutaneous fat samples from 10 nonobese control patients. The
      findings were validated in an independent population of 31 obese women and 9
      obese men and in an animal model of obesity (Lepob/ob mice) by real-time RT-PCR.
      RESULTS: Microarray analysis revealed that transcription factors that regulate
      the first stages of adipocyte differentiation, such as CCAAT/enhancer binding
      protein beta (C/EBPbeta) and JUN, were upregulated in the adipose tissues of
      morbidly obese patients. The expression of peroxisome proliferator-activated
      receptor gamma (PPARgamma), a transcription factor which controls lipid
      metabolism and the final steps of preadipocyte conversion into mature adipocytes,
      was downregulated. The expression of three cyclin-dependent kinase inhibitors
      that regulate clonal expansion and postmitotic growth arrest during adipocyte
      differentiation was also altered in obese subjects: p18 and p27 were
      downregulated, and p21 was upregulated. Angiopoietin-like 4 (ANGPTL4), which
      regulates angiogenesis, lipid and glucose metabolism and it is know to increase
      dramatically in the early stages of adipocyte differentiation, was upregulated.
      The expression of C/EBPbeta, p18, p21, JUN, and ANGPTL4 presented similar
      alterations in subcutaneous adipose tissue of Lepob/ob mice. CONCLUSIONS: Our
      microarray gene profiling study revealed that the expression of genes involved in
      adipogenesis is profoundly altered in the subcutaneous adipose tissue of morbidly
      obese subjects. This expression pattern is consistent with an immature adipocyte
      phenotype that could reflect the expansion of the adipose tissue during obesity.

PMID- 21182759
TI  - The Genomic HyperBrowser: inferential genomics at the sequence level.
AB  - The immense increase in the generation of genomic scale data poses an unmet
      analytical challenge, due to a lack of established methodology with the required
      flexibility and power. We propose a first principled approach to statistical
      analysis of sequence-level genomic information. We provide a growing collection
      of generic biological investigations that query pairwise relations between
      tracks, represented as mathematical objects, along the genome. The Genomic
      HyperBrowser implements the approach and is available at
      http://hyperbrowser.uio.no.

PMID- 21182760
TI  - Activity map of the tammar X chromosome shows that marsupial X inactivation is
      incomplete and escape is stochastic.
AB  - BACKGROUND: X chromosome inactivation is a spectacular example of epigenetic
      silencing. In order to deduce how this complex system evolved, we examined X
      inactivation in a model marsupial, the tammar wallaby (Macropus eugenii). In
      marsupials, X inactivation is known to be paternal, incomplete and tissue
      specific, and occurs in the absence of an XIST orthologue. RESULTS: We examined
      expression of X-borne genes using quantitative PCR, revealing a range of dosage
      compensation for different loci. To assess the frequency of 1X- or 2X-active
      fibroblasts, we investigated expression of 32 X-borne genes at the cellular level
      using RNA-FISH. In female fibroblasts, two-color RNA-FISH showed that genes were
      coordinately expressed from the same X (active X) in nuclei in which both loci
      were inactivated. However, loci on the other X escape inactivation independently,
      with each locus showing a characteristic frequency of 1X-active and 2X-active
      nuclei, equivalent to stochastic escape. We constructed an activity map of the
      tammar wallaby inactive X chromosome, which identified no relationship between
      gene location and extent of inactivation, nor any correlation with the presence
      or absence of a Y-borne paralog. CONCLUSIONS: In the tammar wallaby, one X
      (presumed to be maternal) is expressed in all cells, but genes on the other
      (paternal) X escape inactivation independently and at characteristic frequencies.
      The paternal and incomplete X chromosome inactivation in marsupials, with
      stochastic escape, appears to be quite distinct from the X chromosome
      inactivation process in eutherians. We find no evidence for a polar spread of
      inactivation from an X inactivation center.

PMID- 21182761
TI  - Generation of cell lines to complement adenovirus vectors using recombination
      mediated cassette exchange.
AB  - BACKGROUND: Adenovirus serotype 5 (Ad5) has many favourable characteristics for
      development as a gene therapy vector. However, the utility of current Ad5 vectors
      is limited by transient transgene expression, toxicity and immunogenicity. The
      most promising form of vector is the high capacity type, which is deleted for all
      viral genes. However, these vectors can only be produced to relatively low titres
      and with the aid of helper virus. Therefore a continuing challenge is the
      generation of more effective Ad5 vectors that can still be grown to high titres.
      Our approach is to generate complementing cell lines to support the growth of Ad5
      vectors with novel late gene deficiencies. RESULTS: We have used LoxP/Cre
      recombination mediated cassette exchange (RMCE) to generate cell lines expressing
      Ad5 proteins encoded by the L4 region of the genome, the products of which play a
      pivotal role in the expression of Ad5 structural proteins. A panel of LoxP parent
      293 cell lines was generated, each containing a GFP expression cassette under the
      control of a tetracycline-regulated promoter inserted at a random genome
      location; the cassette also contained a LoxP site between the promoter and GFP
      sequence. Clones displayed a variety of patterns of regulation, stability and
      level of GFP expression. Clone A1 was identified as a suitable parent for
      creation of inducible cell lines because of the tight inducibility and stability
      of its GFP expression. Using LoxP-targeted, Cre recombinase-mediated insertion of
      an L4 cassette to displace GFP from the regulated promoter in this parent clone,
      cell line A1-L4 was generated. This cell line expressed L4 100K, 22K and 33K
      proteins at levels sufficient to complement L4-33K mutant and L4-deleted viruses.
      CONCLUSIONS: RMCE provides a method for rapid generation of Ad5 complementing
      cell lines from a pre-selected parental cell line, chosen for its desirable
      transgene expression characteristics. Parent cell lines can be selected for high
      or low gene expression, and for tight regulation, allowing viral protein
      expression to mirror that found during infection. Cell lines derived from a
      single parent will allow the growth of different vectors to be assessed without
      the complication of varying complementing protein expression.

PMID- 21182762
TI  - Predictive network modeling of the high-resolution dynamic plant transcriptome in
      response to nitrate.
AB  - BACKGROUND: Nitrate, acting as both a nitrogen source and a signaling molecule,
      controls many aspects of plant development. However, gene networks involved in
      plant adaptation to fluctuating nitrate environments have not yet been
      identified. RESULTS: Here we use time-series transcriptome data to decipher gene
      relationships and consequently to build core regulatory networks involved in
      Arabidopsis root adaptation to nitrate provision. The experimental approach has
      been to monitor genome-wide responses to nitrate at 3, 6, 9, 12, 15 and 20
      minutes using Affymetrix ATH1 gene chips. This high-resolution time course
      analysis demonstrated that the previously known primary nitrate response is
      actually preceded by a very fast gene expression modulation, involving genes and
      functions needed to prepare plants to use or reduce nitrate. A state-space model
      inferred from this microarray time-series data successfully predicts gene
      behavior in unlearnt conditions. CONCLUSIONS: The experiments and methods allow
      us to propose a temporal working model for nitrate-driven gene networks. This
      network model is tested both in silico and experimentally. For example, the over
      expression of a predicted gene hub encoding a transcription factor induced early
      in the cascade indeed leads to the modification of the kinetic nitrate response
      of sentinel genes such as NIR, NIA2, and NRT1.1, and several other transcription
      factors. The potential nitrate/hormone connections implicated by this time-series
      data are also evaluated.

PMID- 21182763
TI  - Risk of human exposure to arsenic and other toxic elements from geophagy: trace
      element analysis of baked clay using inductively coupled plasma mass
      spectrometry.
AB  - BACKGROUND: Geophagy or earth-eating is common amongst some Bangladeshi women,
      especially those who are pregnant, both in Bangladesh and in the United Kingdom.
      A large proportion of the population in Bangladesh is already exposed to high
      concentrations of arsenic (As) and other toxic elements from drinking
      contaminated groundwater. Additional exposure to As and other toxic elements from
      non-food sources has not been adequately addressed and here we present the first
      study to monitor As levels in baked clay (known as sikor). METHODS: Sikor samples
      originating from Bangladesh were digested using a microwave digester and analysed
      for their As, Pb, Cd, Mn, Fe and Zn levels using ICP-MS. Detailed As speciation
      analysis was performed using HPLC-ICP-MS. RESULTS: Of particular concern were the
      levels of As (3.8-13.1 mg kg(-1)), Cd (0.09-0.4 mg kg(-1)) and Pb (21-26.7 mg kg(
      1)) present in the sikor samples and their possible impact on human health.
      Speciation analysis revealed that sikor samples contained mainly inorganic As.
      Modest consumption of 50 g of sikor is equivalent to ingesting 370 MUg of As and
      1235 MUg of Pb per day, based on median concentration values. This level of sikor
      consumption exceeds the permitted maximum tolerable daily intake (PMTDI) of
      inorganic As by almost 2-fold. CONCLUSION: We conclude that sikor can be a
      significant source of As, Cd and Pb exposure for the Bangladeshi population
      consuming large quantities of this material. Of particular concern in this regard
      is geophagy practiced by pregnant women concurrently exposed to As contaminated
      drinking water. Future studies needs to evaluate the bioavailability of As and
      other elements from sikor and their impact on human health.

PMID- 21182764
TI  - Concurrent breast stroma sarcoma and breast carcinoma: a case report.
AB  - INTRODUCTION: Breast cancer is one of the most important health problems in the
      world and affects a great number of women over the entire globe. This group of
      tumors rarely presents as bilateral disease and, when it does happen, normally
      occurs within the same histological type. We report a rare case of concurrent
      bilateral breast cancer with two different histology types, a breast carcinoma
      and a breast sarcoma, in a 42-year-old woman referred to our hospital. CASE
      PRESENTATION: A 42-year-old Caucasian woman admitted to our institute in August
      1999, presented with a nodule in the left breast of 3.0 * 2.5 cm, and, in the
      right breast, one of 1.0 cm, suspected of malignancy and with a clinically
      negative armpit. Biopsies had revealed invasive mammary carcinoma (right breast)
      and sarcoma (left breast). She was submitted to bilateral modified radical
      mastectomy. A histological study showed an invasive mammary carcinoma degree II
      lobular pleomorphic type with invasion of seven of the 19 excised axillary nodes
      in the right breast and, in the left breast, a sarcoma of the mammary stroma, for
      which the immunohistochemistry study was negative for epithelial biomarkers and
      positive for vimentin. Later, she was submitted for chemotherapy (six cycles of
      75 mg/m2 5-fluorouracil, epirubicin and cyclophosphamide) followed by
      radiotherapy of the thoracic wall and axillary nodes on the left. Hormone
      receptors were positive in the tumor of the right breast, and tamoxifen, 20 mg,
      was prescribed on a daily basis (five years) followed by letrozole, 2.5 mg, also
      daily (five years). She presented no sign of negative evolution in the last
      consultation. CONCLUSION: The risk of development of bilateral breast cancer is
      about 1% each year within a similar histological type, but it is higher in tumors
      with lobular histology. In this case, the patient presented, simultaneously, two
      histologically distinct tumors, thus evidencing a rare situation.

PMID- 21182765
TI  - Large scale comparison of global gene expression patterns in human and mouse.
AB  - BACKGROUND: It is widely accepted that orthologous genes between species are
      conserved at the sequence level and perform similar functions in different
      organisms. However, the level of conservation of gene expression patterns of the
      orthologous genes in different species has been unclear. To address the issue, we
      compared gene expression of orthologous genes based on 2,557 human and 1,267
      mouse samples with high quality gene expression data, selected from experiments
      stored in the public microarray repository ArrayExpress. RESULTS: In a principal
      component analysis (PCA) of combined data from human and mouse samples merged on
      orthologous probesets, samples largely form distinctive clusters based on their
      tissue sources when projected onto the top principal components. The most
      prominent groups are the nervous system, muscle/heart tissues, liver and cell
      lines. Despite the great differences in sample characteristics and experiment
      conditions, the overall patterns of these prominent clusters are strikingly
      similar for human and mouse. We further analyzed data for each tissue separately
      and found that the most variable genes in each tissue are highly enriched with
      human-mouse tissue-specific orthologs and the least variable genes in each tissue
      are enriched with human-mouse housekeeping orthologs. CONCLUSIONS: The results
      indicate that the global patterns of tissue-specific expression of orthologous
      genes are conserved in human and mouse. The expression of groups of orthologous
      genes co-varies in the two species, both for the most variable genes and the most
      ubiquitously expressed genes.

PMID- 21182766
TI  - A PALB2 mutation associated with high risk of breast cancer.
AB  - NTRODUCTION: As a group, women who carry germline mutations in partner and
      localizer of breast cancer 2 susceptibility protein (PALB2) are at increased risk
      of breast cancer. Little is known about by how much or whether risk differs by
      mutation or family history, owing to the paucity of studies of cases unselected
      for family history. METHODS: We screened 1,403 case probands for PALB2 mutations
      in a population-based study of Australian women with invasive breast cancer
      stratified by age at onset. The age-specific risk of breast cancer was estimated
      from the cancer histories of first- and second-degree relatives of mutation
      carrying probands using a modified segregation analysis that included a polygenic
      modifier and was conditioned on the carrier case proband. Further screening for
      PALB2 c.3113G > A (W1038X) was conducted for 779 families with multiple cases of
      breast cancer ascertained through family cancer clinics in Australia and New
      Zealand and 764 population-based controls. RESULTS: We found five independent
      case probands in the population-based sample with the protein-truncating mutation
      PALB2 c.3113G > A (W1038X); 2 of 695 were diagnosed before age 40 years and 3 of
      708 were diagnosed when between ages 40 and 59 years. Both of the two early-onset
      carrier case probands had very strong family histories of breast cancer. Further
      testing found that the mutation segregated with breast cancer in these families.
      No c.3113G > A (W1038X) carriers were found in 764 population-based unaffected
      controls. The hazard ratio was estimated to be 30.1 (95% confidence interval
      (CI), 7.5 to 120; P < 0.0001), and the corresponding cumulative risk estimates
      were 49% (95% CI, 15 to 93) to age 50 and 91% (95% CI, 44 to 100) to age 70. We
      found another eight families carrying this mutation in 779 families with multiple
      cases of breast cancer ascertained through family cancer clinics. CONCLUSIONS:
      The PALB2 c.3113G > A mutation appears to be associated with substantial risks of
      breast cancer that are of clinical relevance.

PMID- 21182767
TI  - Increased frequency of metabolic syndrome among Vietnamese women with early
      rheumatoid arthritis: a cross-sectional study.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is associated with increased morbidity
      and mortality due to cardiovascular disease, and this occurs early in the disease
      process. The metabolic syndrome (MetS) may contribute to the excess
      cardiovascular burden observed in RA; however, little information is available
      regarding MetS in early RA. We aimed to identify the prevalence of MetS and to
      determine the potential factors associated with the presence of MetS in
      Vietnamese women with early RA. METHODS: A total of 105 consecutive women with
      early RA (disease duration <=3 years) and 105 age-matched healthy women were
      checked for MetS according to six MetS definitions (Joint Consensus,
      International Diabetes Federation, National Cholesterol Education Program 2004
      and 2001, European Group for Study of Insulin Resistance, and World Health
      Organization). Multivariate logistic regression models were constructed to
      determine independent predictors of MetS in women with RA. RESULTS: Prevalence of
      MetS varied from 16.2% to 40.9% according to the definitions used in women with
      RA, and was higher (P < 0.001) than in healthy controls (from 10.5% to 22.9%).
      Among individual components of MetS, differences between women with RA and
      controls were observed for hypertension (P < 0.001), low high density lipoprotein
      cholesterol (HDL-C) levels (P < 0.001), and abdominal obesity (P = 0.019). After
      adjusting for age and physical activity, higher erythrocyte sedimentation rate
      (ESR) (odds ratios (OR) = 1.516, 95% confidence interval (CI): 1.073 to 3.195, P
      = 0.042), disease activity score (DAS28) (OR = 1.736, 95% CI: 1.293 to 2.786, P =
      0.019), health assessment questionnaire (HAQ) score (OR = 1.583, 95% CI: 1.195 to
      2.367, P = 0.035), and less methotrexate use (OR = 0.736, 95% CI: 0.547 to 0.962,
      P = 0.024) remained significant independent predictors of the presence of MetS in
      women with RA. CONCLUSIONS: Women with early RA already had higher prevalence of
      MetS compared with healthy controls. Higher systemic inflammatory marker, disease
      activity and disability scores, and less methotrexate use were independent
      predictors associated with the presence of MetS in women with early RA. These
      findings suggest that physicians should screen for MetS in women with early RA to
      control its components and therefore reduce their risk of cardiovascular
      diseases.

PMID- 21182768
TI  - Homoeolog-specific retention and use in allotetraploid Arabidopsis suecica
      depends on parent of origin and network partners.
AB  - BACKGROUND: Allotetraploids carry pairs of diverged homoeologs for most genes.
      With the genome doubled in size, the number of putative interactions is enormous.
      This poses challenges on how to coordinate the two disparate genomes, and creates
      opportunities by enhancing the phenotypic variation. New combinations of alleles
      co-adapt and respond to new environmental pressures. Three stages of the
      allopolyploidization process--parental species divergence, hybridization, and
      genome duplication--have been well analyzed. The last stage of evolutionary
      adjustments remains mysterious. RESULTS: Homoeolog-specific retention and use
      were analyzed in Arabidopsis suecica (As), a species derived from A. thaliana
      (At) and A. arenosa (Aa) in a single event 12,000 to 300,000 years ago. We used
      405,466 diagnostic features on tiling microarrays to recognize At and Aa
      contributions to the As genome and transcriptome: 324 genes lacked Aa
      contributions and 614 genes lacked At contributions within As. In leaf tissues,
      3,458 genes preferentially expressed At homoeologs while 4,150 favored Aa
      homoeologs. These patterns were validated with resequencing. Genes with
      preferential use of Aa homoeologs were enriched for expression functions,
      consistent with the dominance of Aa transcription. Heterologous networks--mixed
      from At and Aa transcripts--were underrepresented. CONCLUSIONS: Thousands of
      deleted and silenced homoeologs in the genome of As were identified. Since
      heterologous networks may be compromised by interspecies incompatibilities, these
      networks evolve co-biases, expressing either only Aa or only At homoeologs. This
      progressive change towards predominantly pure parental networks might contribute
      to phenotypic variability and plasticity, and enable the species to exploit a
      larger range of environments.

PMID- 21182769
TI  - Evaluation of oral health-related quality of life among Sudanese schoolchildren
      using Child-OIDP inventory.
AB  - BACKGROUND: Information on oral health-related quality of life, in addition to
      clinical measures, is essential for healthcare policy makers to promote oral
      health resources and address oral health needs. OBJECTIVES: This paper aimed at
      evaluating the psychometric properties of the Arabic version of Child-OIDP,
      estimating the prevalence, severity and causes of oral impacts on daily
      performances in 12-year-old public and private school attendees in Khartoum State
      and to identify socio-demographic and clinical correlates of oral impacts as
      assessed by the Child-OIDP inventory. METHODS: The Child-OIDP questionnaire was
      translated into Arabic was administered to a representative sample of 1109
      schoolchildren in Khartoum state. Clinical measures employed in this study
      included DMFT index, Gingival index, Plaque index and Dean's index. A food
      frequency questionnaire was used to study the sugar-sweetened snack consumption.
      RESULTS: The instrument showed acceptable psychometric properties and is
      considered as a valid, reliable (Cronbach's alpha 0.73) and practical inventory
      for use in this population. An impact was reported by 54.6% of the
      schoolchildren. The highest impact was reported on eating (35.5%) followed by
      cleaning (28.3%) and the lowest impacts were on speaking (8.6%) and social
      contact (8.7%). Problems which contributed to all eight impacts were toothache,
      sensitive teeth, exfoliating teeth, swollen gums and bad breath. Toothache was
      the most frequently associated cause of almost all impacts in both private and
      public school attendees. After adjusting for confounders in the 3 multiple
      variable regression models (whole sample, public and private school attendees),
      active caries maintained a significant association with the whole sample (OR 2.0
      95% CI 1.4-2.6) and public school attendees (OR 3.5 95% CI 2.1-5.6), and higher
      SES was associated with only public school attendees' Child-OIDP (OR 1.9 95% 1.1
      3.1). CONCLUSION: This study showed that the Arabic version of the Child-OIDP was
      applicable for use among schoolchildren in Khartoum. Despite the low prevalence
      of the dental caries pathology (24%), a significant relationship, with an average
      moderate intensity was found with OHRQoL. Focus in this population should be on
      oral health education, improving knowledge of the prospective treatment
      opportunities and provision of such services.

PMID- 21182770
TI  - Hydrophobins from Aspergillus species cannot be clearly divided into two classes.
AB  - BACKGROUND: Hydrophobins are a family of small secreted proteins with a
      characteristic pattern of eight cysteine residues found exclusively in
      filamentous fungi. They have originally been divided into two classes based on
      their physical properties and hydropathy patterns, and are involved in the
      attachment of hyphae to hydrophobic structures, the formation of aerial
      structures and appear to be involved in pathogenicity. FINDINGS: Analysis of nine
      genome sequences from seven Aspergilli revealed fifty hydrophobins, where each
      species displayed between two to eight hydrophobins. Twenty of the identified
      hydrophobins have not previously been described from these species. Apart from
      the cysteines, very little amino acid sequence homology was observed. Twenty
      three of the identified hydrophobins could be classified as class I hydrophobins
      based on their conserved cysteine spacing pattern and hydropathy pattern. However
      twenty-six of the identified hydrophobins were intermediate forms. Notably, a
      single hydrophobin, ATEG_04730, from Aspergillus terreus displayed class II
      cysteine spacing and had a class II hydropathy pattern. CONCLUSION: Fifty
      hydrophobins were identified in Aspergillus, all containing the characteristic
      eight cysteine pattern. Aspergillus terreus exhibited both class I and class II
      hydrophobins. This is the first report of an Aspergillus species with the
      potential to express both class I and class II hydrophobins. Many of the
      identified hydrophobins could not directly be allocated to either class I or
      class II.

PMID- 21182771
TI  - ArchAlign: coordinate-free chromatin alignment reveals novel architectures.
AB  - To facilitate identification and characterization of genomic functional elements,
      we have developed a chromatin architecture alignment algorithm (ArchAlign).
      ArchAlign identifies shared chromatin structural patterns from high-resolution
      chromatin structural datasets derived from next-generation sequencing or tiled
      microarray approaches for user defined regions of interest. We validated
      ArchAlign using well characterized functional elements, and used it to explore
      the chromatin structural architecture at CTCF binding sites in the human genome.
      ArchAlign is freely available at
      http://www.acsu.buffalo.edu/~mjbuck/ArchAlign.html.

PMID- 21182772
TI  - Replicative genomics can help Helicobacter fraternity usher in good times.

PMID- 21182773
TI  - Up to seven-fold inter-hospital differences in obstetric anal sphincter injury
      rates- A birth register-based study in Finland.
AB  - BACKGROUND: The occurrence of obstetric anal sphincter injuries (OASIS) - which
      may have serious, long-term effects on affected women, including faecal
      incontinence, despite primary repair - varies widely between countries and have
      been chosen one of the indicators for patient safety in Organisation for Economic
      Cooperation and Development (OECD) countries and in Nordic countries. FINDINGS:
      The aim of the study was to assess risks of OASIS among five university teaching
      hospitals and 14 non-university central hospitals with more than 1,000 deliveries
      annually during 1997-2007 in Finland. Women with singleton vaginal deliveries
      divided into two populations consisting of all 168,637 women from five university
      hospitals and all 255,660 women from non-university hospitals, respectively,
      derived from population-based register. Primiparous and multiparous women with
      OASIS (n = 2,448) were compared in terms of possible risk factors to primiparous
      and multiparous women without OASIS, respectively, using stepwise logistic
      regression analysis. The occurrences of OASIS varied from 0.7% to 2.1% in
      primiparous and from 0.1% to 0.3% in multiparous women among the university
      hospitals. Three-fold inter-hospital differences in OASIS rates did not
      significantly change after adjustment for patient mix or the use of
      interventions. In non-university hospitals OASIS rates varied from 0.2% to 1.4%
      in primiparous and from 0.02% to 0.4% in multiparous women, and the results
      remained virtually unchanged after adjustment for known risks. CONCLUSIONS: Up to
      3.2-fold inter-hospital differences in OASIS risk demonstrates significant
      differences in the quality of Finnish obstetric care.

PMID- 21182774
TI  - Malaria transmission and vector behaviour in a forested malaria focus in central
      Vietnam and the implications for vector control.
AB  - BACKGROUND: In Vietnam, malaria is becoming progressively restricted to specific
      foci where human and vector characteristics alter the known malaria epidemiology,
      urging for alternative or adapted control strategies. Long-lasting insecticidal
      hammocks (LLIH) were designed and introduced in Ninh Thuan province, south
      central Vietnam, to control malaria in the specific context of forest malaria. An
      entomological study in this specific forested environment was conducted to assess
      the behavioural patterns of forest and village vectors and to assess the spatio
      temporal risk factors of malaria transmission in the province. METHODS: Five
      entomological surveys were conducted in three villages in Ma Noi commune and in
      five villages in Phuoc Binh commune in Ninh Thuan Province, south-central
      Vietnam. Collections were made inside the village, at the plot near the slash-and
      burn fields in the forest and on the way to the forest. All collected mosquito
      species were subjected to enzyme-linked immunosorbent assay (ELISA) to detect
      Plasmodium in the head-thoracic portion of individual mosquitoes after
      morphological identification. Collection data were analysed by use of
      correspondence and multivariate analyses. RESULTS: The mosquito density in the
      study area was low with on average 3.7 anopheline bites per man-night and 17.4
      culicine bites per man-night. Plasmodium-infected mosquitoes were only found in
      the forest and on the way to the forest. Malaria transmission in the forested
      malaria foci was spread over the entire night, from dusk to dawn, but was most
      intense in the early evening as nine of the 13 Plasmodium positive bites occurred
      before 21H. The annual entomological inoculation rate of Plasmodium falciparum
      was 2.2 infective bites per person-year to which Anopheles dirus s.s. and
      Anopheles minimus s.s. contributed. The Plasmodium vivax annual entomological
      inoculation rate was 2.5 infective bites per person-year with Anopheles
      sawadwongporni, Anopheles dirus s.s. and Anopheles pampanai as vectors.
      CONCLUSION: The vector behaviour and spatio-temporal patterns of malaria
      transmission in Southeast Asia impose new challenges when changing objectives
      from control to elimination of malaria and make it necessary to focus not only on
      the known main vector species. Moreover, effective tools to prevent malaria
      transmission in the early evening and in the early morning, when the treated bed
      net cannot be used, need to be developed.

PMID- 21182775
TI  - A systematic review of studies measuring health-related quality of life of
      general injury populations.
AB  - BACKGROUND: It is important to obtain greater insight into health-related quality
      of life (HRQL) of injury patients in order to document people's pathways to
      recovery and to quantify the impact of injury on population health over time. We
      performed a systematic review of studies measuring HRQL in general injury
      populations with a generic health state measure to summarize existing knowledge.
      METHODS: Injury studies (1995-2009) were identified with main inclusion criteria
      being the use of a generic health status measure and not being restricted to one
      specific type of injury. Articles were collated by study design, HRQL instrument
      used, timing of assessment(s), predictive variables and ability to detect change
      over time. RESULTS: Forty one studies met inclusion criteria, using 24 different
      generic HRQL and functional status measures (most used were SF-36, FIM, GOS, EQ
      5D). The majority of the studies used a longitudinal design, but with different
      lengths and timings of follow-up (mostly 6, 12, and 24 months). Different generic
      health measures were able to discriminate between the health status of subgroups
      and picked up changes in health status between discharge and 12 month follow-up.
      Most studies reported high prevalences of health problems within the first year
      after injury. The twelve studies that reported HRQL utility scores showed
      considerable but incomplete recovery in the first year after discharge.
      CONCLUSION: This systematic review demonstrates large variation in use of HRQL
      instruments, study populations, and assessment time points used in studies
      measuring HRQL of general injury populations. This variability impedes comparison
      of HRQL summary scores between studies and prevented formal meta-analyses aiming
      to quantify and improve precision of the impact of injury on population health
      over time.

PMID- 21182776
TI  - RNAi-based validation of antibodies for reverse phase protein arrays.
AB  - BACKGROUND: Reverse phase protein arrays (RPPA) have been demonstrated to be a
      useful experimental platform for quantitative protein profiling in a high
      throughput format. Target protein detection relies on the readout obtained from a
      single detection antibody. For this reason, antibody specificity is a key factor
      for RPPA. RNAi allows the specific knockdown of a target protein in complex
      samples and was therefore examined for its utility to assess antibody performance
      for RPPA applications. RESULTS: To proof the feasibility of our strategy, two
      different anti-EGFR antibodies were compared by RPPA. Both detected the knockdown
      of EGFR but at a different rate. Western blot data were used to identify the most
      reliable antibody. The RNAi approach was also used to characterize commercial
      anti-STAT3 antibodies. Out of ten tested anti-STAT3 antibodies, four antibodies
      detected the STAT3-knockdown at 80-85%, and the most sensitive anti-STAT3
      antibody was identified by comparing detection limits. Thus, the use of RNAi for
      RPPA antibody validation was demonstrated to be a stringent approach to identify
      highly specific and highly sensitive antibodies. Furthermore, the RNAi/RPPA
      strategy is also useful for the validation of isoform-specific antibodies as
      shown for the identification of AKT1/AKT2 and CCND1/CCND3-specific antibodies.
      CONCLUSIONS: RNAi is a valuable tool for the identification of very specific and
      highly sensitive antibodies, and is therefore especially useful for the
      validation of RPPA-suitable detection antibodies. On the other hand, when a set
      of well-characterized RPPA-antibodies is available, large-scale RNAi experiments
      analyzed by RPPA might deliver useful information for network reconstruction.

PMID- 21182777
TI  - Systematic review of mass media interventions designed to improve public
      recognition of stroke symptoms, emergency response and early treatment.
AB  - BACKGROUND: Mass media interventions have been implemented to improve emergency
      response to stroke given the emergence of effective acute treatments, but their
      impact is unclear. METHODS: Systematic review of mass media interventions aimed
      at improving emergency response to stroke, with narrative synthesis and review of
      intervention development. RESULTS: Ten studies were included (six targeted the
      public, four both public and professionals) published between 1992 and 2010. Only
      three were controlled before and after studies, and only one had reported how the
      intervention was developed. Campaigns aimed only at the public reported
      significant increase in awareness of symptoms/signs, but little impact on
      awareness of need for emergency response. Of the two controlled before and after
      studies, one reported no impact on those over 65 years, the age group at
      increased risk of stroke and most likely to witness a stroke, and the other found
      a significant increase in awareness of two or more warning signs of stroke in the
      same group post-intervention. One campaign targeted at public and professionals
      did not reduce time to presentation at hospital to within two hours, but
      increased and sustained thrombolysis rates. This suggests the campaign had a
      primary impact on professionals and improved the way that services for stroke
      were organised. CONCLUSIONS: Campaigns aimed at the public may raise awareness of
      symptoms/signs of stroke, but have limited impact on behaviour. Campaigns aimed
      at both public and professionals may have more impact on professionals than the
      public. New campaigns should follow the principles of good design and be robustly
      evaluated.

PMID- 21182778
TI  - Analysis of genomic differences among Clostridium botulinum type A1 strains.
AB  - BACKGROUND: Type A1 Clostridium botulinum strains are a group of Gram-positive,
      spore-forming anaerobic bacteria that produce a genetically, biochemically, and
      biophysically indistinguishable 150 kD protein that causes botulism. The genomes
      of three type A1 C. botulinum strains have been sequenced and show a high degree
      of synteny. The purpose of this study was to characterize differences among these
      genomes and compare these differentiating features with two additional
      unsequenced strains used in previous studies. RESULTS: Several strategies were
      deployed in this report. First, University of Massachusetts Dartmouth laboratory
      Hall strain (UMASS strain) neurotoxin gene was amplified by PCR and sequenced;
      its sequence was aligned with the published ATCC 3502 Sanger Institute Hall
      strain and Allergan Hall strain neurotoxin gene regions. Sequence alignment
      showed that there was a synonymous single nucleotide polymorphism (SNP) in the
      region encoding the heavy chain between Allergan strain and ATCC 3502 and UMASS
      strains. Second, comparative genomic hybridization (CGH) demonstrated that the
      UMASS strain and a strain expected to be derived from ATCC 3502 in the Centers
      for Disease Control and Prevention (CDC) laboratory (ATCC 3502*) differed in gene
      content compared to the ATCC 3502 genome sequence published by the Sanger
      Institute. Third, alignment of the three sequenced C. botulinum type A1 strain
      genomes revealed the presence of four comparable blocks. Strains ATCC 3502 and
      ATCC 19397 share the same genome organization, while the organization of the
      blocks in strain Hall were switched. Lastly, PCR was designed to identify UMASS
      and ATCC 3502* strain genome organizations. The PCR results indicated that UMASS
      strain belonged to Hall type and ATCC 3502* strain was identical to ATCC 3502
      (Sanger Institute) type. CONCLUSIONS: Taken together, C. botulinum type A1
      strains including Sanger Institute ATCC 3502, ATCC 3502*, ATCC 19397, Hall,
      Allergan, and UMASS strains demonstrate differences at the level of the
      neurotoxin gene sequence, in gene content, and in genome arrangement.

PMID- 21182779
TI  - Chemical genetics approach to restoring p27Kip1 reveals novel compounds with
      antiproliferative activity in prostate cancer cells.
AB  - BACKGROUND: The cyclin-dependent kinase (CDK) inhibitor p27(Kip)1 is
      downregulated in a majority of human cancers due to ectopic proteolysis by the
      ubiquitin-proteasome pathway. The expression of p27 is subject to multiple
      mechanisms of control involving several transcription factors, kinase pathways
      and at least three different ubiquitin ligases (SCF(SKP)2, KPC, Pirh2), which
      regulate p27 transcription, translation, protein stability and subcellular
      localization. Using a chemical genetics approach, we have asked whether this
      control network can be modulated by small molecules such that p27 protein
      expression is restored in cancer cells. RESULTS: We developed a cell-based assay
      for measuring the levels of endogenous nuclear p27 in a high throughput screening
      format employing LNCaP prostate cancer cells engineered to overexpress SKP2. The
      assay platform was optimized to Z' factors of 0.48 - 0.6 and piloted by screening
      a total of 7368 chemical compounds. During the course of this work, we discovered
      two small molecules of previously unknown biological activity, SMIP001 and
      SMIP004, which increase the nuclear level of p27 at low micromolar
      concentrations. SMIPs (small molecule inhibitors of p27 depletion) also
      upregulate p21(Cip)1, inhibit cellular CDK2 activity, induce G1 delay, inhibit
      colony formation in soft agar and exhibit preferential cytotoxicity in LNCaP
      cells relative to normal human fibroblasts. Unlike SMIP001, SMIP004 was found to
      downregulate SKP2 and to stabilize p27, although neither SMIP is a proteasome
      inhibitor. Whereas the screening endpoint - nuclear p27 - was robustly modulated
      by the compounds, SMIP-mediated cell cycle arrest and apoptosis were not strictly
      dependent on p27 and p21 - a finding that is explained by parallel inhibitory
      effects of SMIPs on positive cell cycle regulators, including cyclins E and A,
      and CDK4. CONCLUSIONS: Our data provide proof-of-principle that the screening
      platform we developed, using endogenous nuclear p27 as an endpoint, presents an
      effective means of identifying bioactive molecules with cancer selective
      antiproliferative activity. This approach, when applied to larger and more
      diverse sets of compounds with refined drug-like properties, bears the potential
      of revealing both unknown cellular pathways globally impinging on p27 and novel
      leads for chemotherapeutics targeting a prominent molecular defect of human
      cancers.

PMID- 21182780
TI  - Mapping of citrullinated fibrinogen B-cell epitopes in rheumatoid arthritis by
      imaging surface plasmon resonance.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) frequently involves the loss of tolerance
      to citrullinated antigens, which may play a role in pathogenicity. Citrullinated
      fibrinogen is commonly found in inflamed synovial tissue and is a frequent target
      of autoantibodies in RA patients. To obtain insight into the B-cell response to
      citrullinated fibrinogen in RA, its autoepitopes were systematically mapped using
      a new methodology. METHODS: Human fibrinogen was citrullinated in vitro by
      peptidylarginine deiminases (PAD), subjected to proteolysis and the resulting
      peptides were fractionated by ion exchange chromatography. The peptide
      composition of the citrullinated peptide-containing fractions was determined by
      high resolution tandem mass spectrometry. The recognition of these fractions by
      patient sera was subsequently analyzed by imaging surface plasmon resonance on
      microarrays. RESULTS: In total about two-thirds of the 81 arginines of human
      fibrinogen were found to be susceptible to citrullination by the human PAD2, the
      human PAD4 or the rabbit PAD2 enzymes. Citrullination sites were found in all
      three polypeptide chains of fibrinogen, although the alpha-chain appeared to
      contain most of them. The analysis of 98 anti-citrullinated protein antibody
      positive RA sera using the new methodology allowed the identification of three
      major citrullinated epitope regions in human fibrinogen, two in the alpha- and
      one in the beta-chain. CONCLUSIONS: A comprehensive overview of citrullination
      sites in human fibrinogen was generated. The multiplex analysis of peptide
      fractions derived from a post-translationally modified protein, characterized by
      mass spectrometry, with patient sera provides a versatile system for mapping
      modified amino acid-containing epitopes. The citrullinated epitopes of human
      fibrinogen most efficiently recognized by RA autoantibodies are confined to three
      regions of its polypeptides.

PMID- 21182781
TI  - Preoperative dexamethasone reduces postoperative pain, nausea and vomiting
      following mastectomy for breast cancer.
AB  - BACKGROUND: Dexamethasone has been reported to reduce postoperative symptoms
      after different surgical procedures. We evaluated the efficacy of preoperative
      dexamethasone in ameliorating postoperative nausea and vomiting (PONV), and pain
      after mastectomy. METHODS: In this prospective, double-blind, placebo-controlled
      study, 70 patients scheduled for mastectomy with axillary lymph node dissection
      were analyzed after randomization to treatment with 8 mg intravenous
      dexamethasone (n = 35) or placebo (n = 35). All patients underwent standardized
      procedures for general anesthesia and surgery. Episodes of PONV and pain score
      were recorded on a visual analogue scale. Analgesic and antiemetic requirements
      were also recorded. RESULTS: Demographic and medical variables were similar
      between groups. The incidence of PONV was lower in the dexamethasone group at the
      early postoperative evaluation (28.6% vs. 60%; p = 0.02) and at 6 h (17.2% vs.
      45.8%; p = 0.03). More patients in the placebo group required additional
      antiemetic medication (21 vs. 8; p = 0.01). Dexamethasone treatment significantly
      reduced postoperative pain just after surgery (VAS score, 4.54 +/- 1.55 vs. 5.83
      +/- 2.00; p = 0.004), at 6 h (3.03 +/- 1.20 vs. 4.17 +/- 1.24; p < 0.0005) and at
      12 h (2.09 +/- 0.85 vs. 2.54 +/- 0.98; p = 0.04). Analgesics were required in
      more patients of the control group (21 vs. 10; p = 0.008). There were no adverse
      events, morbidity or mortality. CONCLUSIONS: Preoperative intravenous
      dexamethasone (8 mg) can significantly reduce the incidence of PONV and pain in
      patients undergoing mastectomy with axillary dissection for breast cancer. TRIAL
      REGISTRATION NUMBER: NCT01116713.

PMID- 21182782
TI  - Eukaryotic signaling pathways targeted by Salmonella effector protein AvrA in
      intestinal infection in vivo.
AB  - BACKGROUND: The Salmonella AvrA gene is present in 80% of Salmonella enterica
      serovar strains. AvrA protein mimics the activities of some eukaryotic proteins
      and uses these activities to the pathogen's advantage by debilitating the target
      cells, such as intestinal epithelial cells. Therefore, it is important to
      understand how AvrA works in targeting eukaryotic signaling pathways in
      intestinal infection in vivo. In this study, we hypothesized that AvrA interacts
      with multiple stress pathways in eukaryotic cells to manipulate the host defense
      system. A whole genome approach combined with bioinformatics assays was used to
      investigate the in vivo genetic responses of the mouse colon to Salmonella with
      or without AvrA protein expression in the early stage (8 hours) and late stage (4
      days). Specifically, we examined the gene expression profiles in mouse colon as
      it responded to pathogenic Salmonella stain SL1344 (with AvrA expression) or
      SB1117 (without AvrA expression). RESULTS: We identified the eukaryotic targets
      of AvrA and the cell signaling pathways regulated by AvrA in vivo. We found that
      pathways, such as mTOR, NF-kappaB, platelet-derived growth factors, vascular
      endothelial growth factor, oxidative phosphorylation, and mitogen-activated
      protein kinase signaling are specifically regulated by AvrA in vivo and are
      associated with inflammation, anti-apoptosis, and proliferation. At the early
      stage of Salmonella infection, AvrA mainly targeted pathways related to nuclear
      receptor signaling and oxidative phosphorylation. At the late stage of Salmonella
      infection, AvrA is associated with interferon-gamma responses. CONCLUSION: Both
      early and late phases of the host response exhibit remarkable specificity for the
      AvrA+ Salmonella. Our studies provide new insights into the eukaryotic molecular
      cascade that combats Salmonella-associated intestinal infection in vivo.

PMID- 21182783
TI  - Levosimendan for resuscitating the microcirculation in patients with septic
      shock: a randomized controlled study.
AB  - INTRODUCTION: The purpose of the present study was to investigate
      microcirculatory blood flow in patients with septic shock treated with
      levosimendan as compared to an active comparator drug (i.e. dobutamine). The
      primary end point was a difference of >= 20% in the microvascular flow index of
      small vessels (MFIs) among groups. METHODS: The study was designed as a
      prospective, randomized, double-blind clinical trial and performed in a
      multidisciplinary intensive care unit. After achieving normovolemia and a mean
      arterial pressure of at least 65 mmHg, 40 septic shock patients were randomized
      to receive either levosimendan 0.2 MUg.kg(-1).min(-1) (n = 20) or an active
      comparator (dobutamine 5 MUg.kg(-1).min(-1); control; n = 20) for 24 hours.
      Sublingual microcirculatory blood flow of small and medium vessels was assessed
      by sidestream dark-field imaging. Microcirculatory variables and data from right
      heart catheterization were obtained at baseline and 24 hours after randomization.
      Baseline and demographic data were compared by means of Mann-Whitney rank sum
      test or chi-square test, as appropriate. Microvascular and hemodynamic variables
      were analyzed using the Mann-Whitney rank sum test. RESULTS: Microcirculatory
      flow indices of small and medium vessels increased over time and were
      significantly higher in the levosimendan group as compared to the control group
      (24 hrs: MFIm 3.0 (3.0; 3.0) vs. 2.9 (2.8; 3.0); P = .02; MFIs 2.9 (2.9; 3.0) vs.
      2.7 (2.3; 2.8); P < .001). The relative increase of perfused vessel density vs.
      baseline was significantly higher in the levosimendan group than in the control
      group (dMFIm 10 (3; 23)% vs. 0 (-1; 9)%; P = .007; dMFIs 47 (26; 83)% vs. 10 (-3;
      27); P < .001). In addition, the heterogeneity index decreased only in the
      levosimendan group (dHI -93 (-100; -84)% vs. 0 (-78; 57)%; P < .001). There was
      no statistically significant correlation between systemic and microcirculatory
      flow variables within each group (each P > .05). CONCLUSIONS: Compared to a
      standard dose of 5 MUg.kg(-1).min(-1) of dobutamine, levosimendan at 0.2 MUg.kg(
      1).min(-1) improved sublingual microcirculatory blood flow in patients with
      septic shock, as reflected by changes in microcirculatory flow indices of small
      and medium vessels. TRIAL REGISTRATION: NCT00800306.

PMID- 21182784
TI  - Lack of the pattern recognition molecule mannose-binding lectin increases
      susceptibility to influenza A virus infection.
AB  - BACKGROUND: Mannose-binding lectin (MBL), a pattern recognition innate immune
      molecule, inhibits influenza A virus infection in vitro. MBL deficiency due to
      gene polymorphism in humans has been associated with infection susceptibility.
      These clinical observations were confirmed by animal model studies, in which mice
      genetically lacking MBL were susceptible to certain pathogens, including herpes
      simplex virus 2. RESULTS: We demonstrate that MBL is present in the lung of naive
      healthy wild type (WT) mice and that MBL null mice are more susceptible to IAV
      infection. Administration of recombinant human MBL (rhMBL) reverses the infection
      phenotype, confirming that the infection susceptibility is MBL-mediated. The anti
      viral mechanisms of MBL include activation of the lectin complement pathway and
      coagulation, requiring serum factors. White blood cells (WBCs) in the lung
      increase in WT mice compared with MBL null mice on day 1 post-infection. In
      contrast, apoptotic macrophages (MPhis) are two-fold higher in the lung of MBL
      null mice compared with WT mice. Furthermore, MBL deficient macrophages appear to
      be susceptible to apoptosis in vitro. Lastly, soluble factors, which are
      associated with lung injury, are increased in the lungs of MBL null mice during
      IAV infection. These results suggest that MBL plays a key role against IAV
      infection. CONCLUSION: MBL plays a key role in clearing IAV and maintaining lung
      homeostasis. In addition, our findings also suggest that MBL deficiency maybe a
      risk factor in IAV infection and MBL may be a useful adjunctive therapy for IAV
      infection.

PMID- 21182785
TI  - Sex-related differences in motor learning and performance.
AB  - Gender differences have been shown across many domains, and motor skills are no
      exception. One of the most robust findings is a significant sex difference in
      throwing accuracy, which reflects the advantage of men in targeting abilities.
      However, little is known about the basis of this difference. To try to dissect
      possible mechanisms involved in this difference, here we tested for gender
      variations in a prism adaptation throwing task. We tested 154 subjects in a
      visuomotor prism adaptation task that discriminates between motor performance,
      visuomotor adaptation and negative aftereffects. Our results corroborate men's
      significant better throwing accuracy, although there were no adaptation
      differences between genders. In contrast, women showed significant larger
      negative aftereffects, which could be explained by a larger contribution of
      spatial alignment. These results suggest that different learning mechanisms, like
      strategic calibration and spatial alignment, may have different contributions in
      men and women.

PMID- 21182786
TI  - Pathogenic effect of interleukin-17A in induction of Sjogren's syndrome-like
      disease using adenovirus-mediated gene transfer.
AB  - INTRODUCTION: Sjogren's syndrome (SS) involves a chronic, progressive
      inflammation primarily of the salivary and lacrimal glands leading to decreased
      levels of saliva and tears resulting in dry mouth and dry eye diseases. Seminal
      findings regarding TH17 cell populations that secrete predominantly interleukin
      (IL)-17A have been shown to play an important role in an increasing number of
      autoimmune diseases, including SS. In the present study, we investigated the
      function of IL-17A on the development and onset of SS. METHODS: Adenovirus
      serotype 5 (Ad5) vectors expressing either IL-17A or LacZ were infused via
      retrograde cannulation into the salivary glands of C57BL/6J mice between 6 and 8
      weeks of age or between 15 and 17 weeks of age. The mice were characterized for
      SS phenotypes. RESULTS: Disease profiling indicated that SS-non-susceptible
      C57BL/6J mice whose salivary glands received the Ad5-IL17A vector developed a SS
      like disease profile, including the appearance of lymphocytic foci, increased
      cytokine levels, changes in antinuclear antibody profiles, and temporal loss of
      saliva flow. CONCLUSIONS: Induction of SS pathology by IL-17A in SS-non
      susceptible mice strongly suggests that IL-17A is an important inflammatory
      cytokine in salivary gland dysfunction. Thus, localized anti-IL17 therapy may be
      effective in preventing glandular dysfunction.

PMID- 21182787
TI  - Protecting the malaria drug arsenal: halting the rise and spread of amodiaquine
      resistance by monitoring the PfCRT SVMNT type.
AB  - The loss of chloroquine due to selection and spread of drug resistant Plasmodium
      falciparum parasites has greatly impacted malaria control, especially in highly
      endemic areas of Africa. Since chloroquine removal a decade ago, the guidelines
      to treat falciparum malaria suggest combination therapies, preferentially with an
      artemisinin derivative. One of the recommended partner drugs is amodiaquine, a
      pro-drug that relies on its active metabolite monodesethylamodiaquine, and is
      still effective in areas of Africa, but not in regions of South America. Genetic
      studies on P. falciparum parasites have shown that different pfcrt mutant
      haplotypes are linked to distinct levels of chloroquine and amodiaquine
      responses. The pfcrt haplotype SVMNT (termed after the amino acids from codon
      positions 72-76) is stably present in several areas where amodiaquine was
      introduced and widely used. Parasites with this haplotype are highly resistant to
      monodesethylamodiaquine and also resistant to chloroquine. The presence of this
      haplotype in Africa was found for the first time in 2004 in Tanzania and a role
      for amodiaquine in the selection of this haplotype was suggested. This commentary
      discusses the finding of a second site in Africa with high incidence of this
      haplotype. The >50% SVMNT haplotype prevalence in Angola represents a threat to
      the rise and spread of amodiaquine resistance. It is paramount to monitor pfcrt
      haplotypes in every country currently using amodiaquine and to re-evaluate
      current combination therapies in areas where SVMNT type parasites are prevalent.

PMID- 21182788
TI  - Constraint-based modeling analysis of the metabolism of two Pelobacter species.
AB  - BACKGROUND: Pelobacter species are commonly found in a number of subsurface
      environments, and are unique members of the Geobacteraceae family. They are
      phylogenetically intertwined with both Geobacter and Desulfuromonas species.
      Pelobacter species likely play important roles in the fermentative degradation of
      unusual organic matters and syntrophic metabolism in the natural environments,
      and are of interest for applications in bioremediation and microbial fuel cells.
      RESULTS: In order to better understand the physiology of Pelobacter species,
      genome-scale metabolic models for Pelobacter carbinolicus and Pelobacter
      propionicus were developed. Model development was greatly aided by the
      availability of models of the closely related Geobacter sulfurreducens and G.
      metallireducens. The reconstructed P. carbinolicus model contains 741 genes and
      708 reactions, whereas the reconstructed P. propionicus model contains 661 genes
      and 650 reactions. A total of 470 reactions are shared among the two Pelobacter
      models and the two Geobacter models. The different reactions between the
      Pelobacter and Geobacter models reflect some unique metabolic capabilities such
      as fermentative growth for both Pelobacter species. The reconstructed Pelobacter
      models were validated by simulating published growth conditions including
      fermentations, hydrogen production in syntrophic co-culture conditions, hydrogen
      utilization, and Fe(III) reduction. Simulation results matched well with
      experimental data and indicated the accuracy of the models. CONCLUSIONS: We have
      developed genome-scale metabolic models of P. carbinolicus and P. propionicus.
      These models of Pelobacter metabolism can now be incorporated into the growing
      repertoire of genome scale models of the Geobacteraceae family to aid in
      describing the growth and activity of these organisms in anoxic environments and
      in the study of their roles and interactions in the subsurface microbial
      community.

PMID- 21182789
TI  - Identification of BACE1 cleavage sites in human voltage-gated sodium channel beta
      2 subunit.
AB  - BACKGROUND: The voltage-gated sodium channel beta2 subunit (Navbeta2) is a
      physiological substrate of BACE1 (beta-site APP cleaving enzyme) and gamma
      secretase, two proteolytic enzymes central to Alzheimer's disease pathogenesis.
      Previously, we have found that the processing of Navbeta2 by BACE1 and gamma
      secretase regulates sodium channel metabolism in neuronal cells. In the current
      study we identified the BACE1 cleavage sites in human Navbeta2. RESULTS: We found
      a major (147-148 L?M, where ? indicates the cleavage site) and a minor (144145
      L?Q) BACE1 cleavage site in the extracellular domain of human Navbeta2 using a
      cell-free BACE1 cleavage assay followed by mass spectrometry. Next, we introduced
      two different double mutations into the identified major BACE1 cleavage site in
      human Navbeta2: 147LM/VI and 147LM/AA. Both mutations dramatically decreased the
      cleavage of human Navbeta2 by endogenous BACE1 in cell-free BACE1 cleavage
      assays. Neither of the two mutations affected subcellular localization of
      Navbeta2 as confirmed by confocal fluorescence microscopy and subcellular
      fractionation of cholesterol-rich domains. Finally, wildtype and mutated Navbeta2
      were expressed along BACE1 in B104 rat neuroblastoma cells. In spite of alpha
      secretase still actively cleaving the mutant proteins, Navbeta2 cleavage products
      decreased by ~50% in cells expressing Navbeta2 (147LM/VI) and ~75% in cells
      expressing Navbeta2 (147LM/AA) as compared to cells expressing wildtype Navbeta2.
      CONCLUSION: We identified a major (147-148 L?M) and a minor (144-145 L?Q) BACE1
      cleavage site in human Navbeta2. Our in vitro and cell-based results clearly show
      that the 147-148 L?M is the major BACE1 cleavage site in human Navbeta2. These
      findings expand our understanding of the role of BACE1 in voltage-gated sodium
      channel metabolism.

PMID- 21182790
TI  - Investigating concordance in diabetes diagnosis between primary care charts
      (electronic medical records) and health administrative data: a retrospective
      cohort study.
AB  - BACKGROUND: Electronic medical records contain valuable clinical information not
      readily available elsewhere. Accordingly, they hold important potential for
      contributing to and enhancing chronic disease registries with the goal of
      improving chronic disease management; however a standard for diagnoses of
      conditions such as diabetes remains to be developed. The purpose of this study
      was to establish a validated electronic medical record definition for diabetes.
      METHODS: We constructed a retrospective cohort using health administrative data
      from the Institute for Clinical Evaluative Sciences Ontario Diabetes Database
      linked with electronic medical records from the Deliver Primary Healthcare
      Information Project using data from 1 April 2006-31 March 2008 (N = 19,443). We
      systematically examined eight definitions for diabetes diagnosis, both
      established and proposed. RESULTS: The definition that identified the highest
      number of patients with diabetes (N = 2,180) while limiting to those with the
      highest probability of having diabetes was: individuals with >=2 abnormal plasma
      glucose tests, or diabetes on the problem list, or insulin prescription, or >=2
      oral anti-diabetic agents, or HbA1c >=6.5%. Compared to the Ontario Diabetes
      Database, this definition identified 13% more patients while maintaining good
      sensitivity (75%) and specificity (98%). CONCLUSIONS: This study establishes the
      feasibility of developing an electronic medical record standard definition of
      diabetes and validates an algorithm for use in this context. While the algorithm
      may need to be tailored to fit available data in different electronic medical
      records, it contributes to the establishment of validated disease registries with
      the goal of enhancing research, and enabling quality improvement in clinical care
      and patient self-management.

PMID- 21182792
TI  - The Survey of the Health of Wisconsin (SHOW), a novel infrastructure for
      population health research: rationale and methods.
AB  - BACKGROUND: Evidence-based public health requires the existence of reliable
      information systems for priority setting and evaluation of interventions.
      Existing data systems in the United States are either too crude (e.g., vital
      statistics), rely on administrative data (e.g., Medicare) or, because of their
      national scope (e.g., NHANES), lack the discriminatory power to assess specific
      needs and to evaluate community health activities at the state and local level.
      This manuscript describes the rationale and methods of the Survey of the Health
      of Wisconsin (SHOW), a novel infrastructure for population health research.
      METHODS/DESIGN: The program consists of a series of independent annual surveys
      gathering health-related data on representative samples of state residents and
      communities. Two-stage cluster sampling is used to select households and recruit
      approximately 800-1,000 adult participants (21-74 years old) each year.
      Recruitment and initial interviews are done at the household; additional
      interviews and physical exams are conducted at permanent or mobile examination
      centers. Individual survey data include physical, mental, and oral health
      history, health literacy, demographics, behavioral, lifestyle, occupational, and
      household characteristics as well as health care access and utilization. The
      physical exam includes blood pressure, anthropometry, bioimpedance, spirometry,
      urine collection and blood draws. Serum, plasma, and buffy coats (for DNA
      extraction) are stored in a biorepository for future studies. Every household is
      geocoded for linkage with existing contextual data including community level
      measures of the social and physical environment; local neighborhood
      characteristics are also recorded using an audit tool. Participants are re
      contacted bi-annually by phone for health history updates. DISCUSSION: SHOW
      generates data to assess health disparities across state communities as well as
      trends on prevalence of health outcomes and determinants. SHOW also serves as a
      platform for ancillary epidemiologic studies and for studies to evaluate the
      effect of community-specific interventions. It addresses key gaps in our current
      data resources and increases capacity for etiologic, applied and translational
      population health research. It is hoped that this program will serve as a model
      to better support evidence-based public health, facilitate intervention
      evaluation research, and ultimately help improve health throughout the state and
      nation.

PMID- 21182791
TI  - In search of quality evidence for lifestyle management and glycemic control in
      children and adolescents with type 2 diabetes: A systematic review.
AB  - BACKGROUND: Our purpose was to evaluate the impact of lifestyle behavior
      modification on glycemic control among children and youth with clinically defined
      Type 2 Diabetes (T2D). METHODS: We conducted a systematic review of studies
      (randomized trials, quasi-experimental studies) evaluating lifestyle (diet and/or
      physical activity) modification and glycemic control (HbA1c). Our data sources
      included bibliographic databases (EMBASE, CINAHL(r), Cochrane Library,
      Medline(r), PASCAL, PsycINFO(r), and Sociological Abstracts), manual reference
      search, and contact with study authors. Two reviewers independently selected
      studies that included any intervention targeting diet and/or physical activity
      alone or in combination as a means to reduce HbA1c in children and youth under
      the age of 18 with T2D. RESULTS: Our search strategy generated 4,572 citations.
      The majority of citations were not relevant to the study objective. One study met
      inclusion criteria. In this retrospective study, morbidly obese youth with T2D
      were treated with a very low carbohydrate diet. This single study received a
      quality index score of < 11, indicating poor study quality and thus limiting
      confidence in the study's conclusions. CONCLUSIONS: There is no high quality
      evidence to suggest lifestyle modification improves either short- or long-term
      glycemic control in children and youth with T2D. Additional research is clearly
      warranted to define optimal lifestyle behaviour strategies for young people with
      T2D.

PMID- 21182793
TI  - Investigating effects of parasite infection on body condition of the Kafue lechwe
      (Kobus leche kafuensis) in the Kafue basin.
AB  - BACKGROUND: The Kafue lechwe (Kobus leche Kafuensis), a medium-sized semi-aquatic
      antelope, is endemic to the Kafue basin of Zambia. The population of the Kafue
      lechwe has significantly dropped in the last decades leading to its subsequent
      inclusion on the red list of endangered species. In order to save the remaining
      population from extinction, it has become increasingly important that the impact
      of parasite infection and infestation on the Kafue lechwe is investigated.
      FINDINGS: Endoparasites accounted for the majority of parasites observed from a
      study of 40 Kafue lechwe occurring in the the Kafue basin. Amphistoma spp. were
      present in all animals examined, while Fasciola gigantica had a prevalence rate
      of 0.525 (95% CI: 0.36 to 0.69) and species of Schistosoma 0.3 (95% CI: 0.15 to
      0.45). Among the ectoparasites, Strobiloestrous vanzyli, had a prevalence rate of
      0.15 (95% CI: 0.03 to 0.27), while Rhipicephalus appendiculatus had a prevalence
      of 0.075 (3/40). Our findings indicate that body condition was not influenced by
      the parasitic infestation in Kafue lechwe. There was no association between sex
      and parasitic burden (odds ratio = 0.3, 95% CI: 0.8-1.3). However, an association
      between age and parasitic burden was observed as older animals above 15 years
      were more likely to get parasite infections than those aged between 1-5 years
      (odds ratio = 1.5, 95% CI: 1.1-2.4). CONCLUSION: Overall, there was no evidence
      that parasitic infections and infestations adversely affected the lechwe
      population on the Kafue basin. These findings indicate that ecto- and endo
      parasite infestation might not play a significant role in reducing the Kafue
      lechwe population on the Kafue basin.

PMID- 21182794
TI  - Estimated intelligence quotient in anorexia nervosa: a systematic review and meta
      analysis of the literature.
AB  - BACKGROUND: It has been hypothesised that people with anorexia nervosa have a
      higher intelligence quotient (IQ) level than the general population. The purpose
      of this review was to systematically appraise the research into reported IQ
      levels in people with anorexia nervosa. METHODS: A search using the terms
      intelligence quotient, IQ, intelligence, cognition, eating disorders and anorexia
      was conducted in electronic databases only. RESULTS: In all, 30 peer-reviewed
      studies written in English that used well established measures of intelligence
      quotient (the National Adult Reading Test and Wechsler Intelligence Scales) were
      identified. This review established that people with anorexia nervosa score 10.8
      units and 5.9 units above the average intelligence quotient of the normative
      population on the National Adult Reading Test and Wechsler Intelligence Scales,
      respectively. An association was found between Body Mass Index and intelligence
      quotient, as measured by the National Adult Reading Test. CONCLUSIONS: More
      studies including other eating disorder categories and recovered people are
      needed to explore important questions regarding the role of the intelligence
      quotient in treatment response.

PMID- 21182795
TI  - Phosphorylation meets nuclear import: a review.
AB  - Phosphorylation is the most common and pleiotropic modification in biology,
      which plays a vital role in regulating and finely tuning a multitude of
      biological pathways. Transport across the nuclear envelope is also an essential
      cellular function and is intimately linked to many degeneration processes that
      lead to disease. It is therefore not surprising that phosphorylation of cargos
      trafficking between the cytoplasm and nucleus is emerging as an important step to
      regulate nuclear availability, which directly affects gene expression, cell
      growth and proliferation. However, the literature on phosphorylation of
      nucleocytoplasmic trafficking cargos is often confusing. Phosphorylation, and its
      mirror process dephosphorylation, has been shown to have opposite and often
      contradictory effects on the ability of cargos to be transported across the
      nuclear envelope. Without a clear connection between attachment of a phosphate
      moiety and biological response, it is difficult to fully understand and predict
      how phosphorylation regulates nucleocytoplasmic trafficking. In this review, we
      will recapitulate clue findings in the field and provide some general rules on
      how reversible phosphorylation can affect the nuclear-cytoplasmic localization of
      substrates. This is only now beginning to emerge as a key regulatory step in
      biology.

PMID- 21182797
TI  - Improving the uptake of preconception care and periconceptional folate
      supplementation: what do women think?
AB  - BACKGROUND: Despite strong evidence of the benefits of preconception
      interventions to improve pregnancy outcomes, the delivery and uptake of
      preconception care in general and periconceptional folate supplementation in
      particular remains low. The aim of this study was to determine women's views of
      the barriers and enablers to the uptake of preconception care and
      periconceptional folate supplementation. METHODS: Focus groups were undertaken in
      2007 with 17 women of reproductive age (18-45 years). To identify key issues and
      themes within the data, focus groups were analysed using an inductive process of
      thematic analysis. RESULTS: Most women were unaware of the need to attend for
      preconception care and were surprised at the breadth of issues involved. Women
      also felt general practitioners (GPs) should be more proactive in promoting
      preconception care availability but acknowledged that they themselves had to be
      thinking about pregnancy or becoming pregnant to be receptive to it. Barriers to
      periconceptional folate supplementation included confusion about reasons for use,
      dose, duration, timing and efficacy of folate use. Enablers included the desire
      to do anything they could to ensure optimum pregnancy outcomes, and promotional
      material and letters of invitation from their GP to advise them of the
      availability and the need for preconception care. CONCLUSION: A number of
      important barriers and enablers exist for women regarding the delivery and uptake
      of preconception care and periconceptional folate supplementation. It is
      essential that these patient perspectives are addressed in both the
      implementation of evidence based clinical practice guidelines and in the
      systematic design of an intervention to improve preconception care delivery.

PMID- 21182796
TI  - Trends in CD4 counts in HIV-infected patients with HIV viral load monitoring
      while on combination antiretroviral treatment: results from The TREAT Asia HIV
      Observational Database.
AB  - BACKGROUND: The aim of this study was to examine the relationship between trends
      in CD4 counts (slope) and HIV viral load (VL) after initiation of combination
      antiretroviral treatment (cART) in Asian patients in The TREAT Asia HIV
      Observational Database (TAHOD). METHODS: Treatment-naive HIV-infected patients
      who started cART with three or more and had three or more CD4 count and HIV VL
      tests were included. CD4 count slopes were expressed as changes of cells per
      microliter per year. Predictors of CD4 count slopes from 6 months after
      initiation were assessed by random-effects linear regression models. RESULTS: A
      total of 1676 patients (74% male) were included. The median time on cART was 4.2
      years (IQR 2.5-5.8 years). In the final model, CD4 count slope was associated
      with age, concurrent HIV VL and CD4 count, disease stage, hepatitis B or C co
      infection, and time since cART initiation. CD4 count continues to increase with
      HIV VL up to 20,000 copies/mL during 6-12 months after cART initiation. However,
      the HIV VL has to be controlled below 5,000, 4,000 and 500 copies/mL for the CD4
      count slope to remain above 20 cells/microliter per year during 12-18, 18-24, and
      beyond 24 months after cART initiation. CONCLUSIONS: After cART initiation, CD4
      counts continued to increase even when the concurrent HIV VL was detectable.
      However, HIV VL needed to be controlled at a lower level to maintain a positive
      CD4 count slope when cART continues. The effect on long-term outcomes through the
      possible development of HIV drug resistance remains uncertain.

PMID- 21182798
TI  - Impact on cell to plasma ratio of miR-92a in patients with acute leukemia: in
      vivo assessment of cell to plasma ratio of miR-92a.
AB  - BACKGROUND: Plasma microRNA (miRNA) has become a promising biomarker for
      detecting cancer; however, it remains uncertain whether miRNA expression levels
      in plasma reflect those in tumor cells. Our aim was to determine the biological
      relevance of miR-92a, which has been implicated as an oncomiR in both plasma and
      leukemia cells in patients with acute leukemia and to evaluate whether it could
      be a novel biomarker for monitoring these patients. RESULTS: We quantified the
      expression level of miR-92a in both cells and plasma by reverse transcription
      polymerase chain reaction in 91 patients with acute leukemia. We also determined
      miR-92a expression levels in peripheral blood mononuclear cells (PBMNC) from
      normal controls. We compared miR-92a expression in plasma with its expression in
      leukemia cells. Synthetic anti-miR-92a inhibitor was transfected into Raji and
      OM9;22 cells, and apoptosis was assessed. For in vivo assessment, 6-week-old
      female nude mice were injected with U937 cells, and miR-92a expression in plasma
      and tumors was measured. The level of miR-92a expression in fresh leukemia cells
      was highly variable compared with PBMNC, but significantly lower compared with
      CD34-positive cells obtained from healthy volunteers. We also noticed that miR
      92a was preferentially expressed in acute lymphoblastic leukemia (ALL) cells in
      comparison with acute myeloid leukemia (AML) cells. More specifically, cellular
      miR-92a expression was significantly increased in a subset of ALL cells, and ALL
      patients with overexpressed miR-92a had poor prognoses. The anti-miR-92a
      inhibitor-treated Raji and OM9;22 cells revealed an increase of apoptotic cells.
      Notably, the cell to plasma ratio of miR-92a expression was significantly higher
      in both AML and ALL cells compared with PBMNC from healthy volunteers. In tumor
      bearing mice, the plasma miR-92a level was significantly decreased in accordance
      with tumor growth, while tumor tissue was strongly positive for miR-92a.
      CONCLUSIONS: The miR-92a expression in leukemia cells could be a prognostic
      factor in ALL patients. The inverse correlation of miR-92a expression between
      cells and plasma and the cell to plasma ratio may be important to understanding
      the clinical and biological relevance of miR-92a in acute leukemia.

PMID- 21182799
TI  - Treatment results and prognostic factors of pediatric neuroblastoma: a
      retrospective study.
AB  - BACKGROUND: We conducted a retrospective analysis to investigate treatment
      results and prognostic factors of pediatric neuroblastoma patients. METHODS: This
      retrospective study was carried out analyzing the medical records of patients
      with the pathological diagnosis of neuroblastoma seen at South Egypt Cancer
      Institute, Assiut University during the period from January 2001 and January
      2010. After induction chemotherapy, response according to international
      neuoblastoma response criteria was assessed. Radiotherapy to patients with
      residual primary tumor was applied. Overall and event free survival (OAS and EFS)
      rates were estimated using Graphed prism program. The Log-rank test was used to
      examine differences in OAS and EFS rates. Cox-regression multivariate analysis
      was done to determine the independent prognostic factors affecting survival
      rates. RESULTS: Fifty three cases were analyzed. The median follow-up duration
      was 32 months and ranged from 2 to 84 months. The 3-year OAS and EFS rates were
      39.4% and 29.3% respectively. Poor prognostic factors included age >1 year of
      age, N-MYC amplification, and high risk group. The majority of patients (68%)
      presented in high risk group, where treatment outcome was poor, as only 21% of
      patients survived for 3 year. CONCLUSION: Multivariate analysis confirmed only
      the association between survival and risk group. However, in univariate analysis,
      local radiation therapy resulted in significant survival improvement. Therefore,
      radiotherapy should be given to patients with residual tumor evident after
      induction chemotherapy and surgery. Future attempts to improve OAS in high risk
      group patients with aggressive chemotherapy and bone marrow transplantation
      should be considered.

PMID- 21182800
TI  - De novo assembly and characterization of root transcriptome using Illumina paired
      end sequencing and development of cSSR markers in sweet potato (Ipomoea batatas).
AB  - BACKGROUND: The tuberous root of sweet potato is an important agricultural and
      biological organ. There are not sufficient transcriptomic and genomic data in
      public databases for understanding of the molecular mechanism underlying the
      tuberous root formation and development. Thus, high throughput transcriptome
      sequencing is needed to generate enormous transcript sequences from sweet potato
      root for gene discovery and molecular marker development. RESULTS: In this study,
      more than 59 million sequencing reads were generated using Illumina paired-end
      sequencing technology. De novo assembly yielded 56,516 unigenes with an average
      length of 581 bp. Based on sequence similarity search with known proteins, a
      total of 35,051 (62.02%) genes were identified. Out of these annotated unigenes,
      5,046 and 11,983 unigenes were assigned to gene ontology and clusters of
      orthologous group, respectively. Searching against the Kyoto Encyclopedia of
      Genes and Genomes Pathway database (KEGG) indicated that 17,598 (31.14%) unigenes
      were mapped to 124 KEGG pathways, and 11,056 were assigned to metabolic pathways,
      which were well represented by carbohydrate metabolism and biosynthesis of
      secondary metabolite. In addition, 4,114 cDNA SSRs (cSSRs) were identified as
      potential molecular markers in our unigenes. One hundred pairs of PCR primers
      were designed and used for validation of the amplification and assessment of the
      polymorphism in genomic DNA pools. The result revealed that 92 primer pairs were
      successfully amplified in initial screening tests. CONCLUSION: This study
      generated a substantial fraction of sweet potato transcript sequences, which can
      be used to discover novel genes associated with tuberous root formation and
      development and will also make it possible to construct high density microarrays
      for further characterization of gene expression profiles during these processes.
      Thousands of cSSR markers identified in the present study can enrich molecular
      markers and will facilitate marker-assisted selection in sweet potato breeding.
      Overall, these sequences and markers will provide valuable resources for the
      sweet potato community. Additionally, these results also suggested that
      transcriptome analysis based on Illumina paired-end sequencing is a powerful tool
      for gene discovery and molecular marker development for non-model species,
      especially those with large and complex genome.

PMID- 21182802
TI  - Self-administered questionnaire versus interview as a screening method for
      intimate partner violence in the prenatal setting in Japan: a randomised
      controlled trial.
AB  - BACKGROUND: Intimate partner violence (IPV) is a serious social issue in Japan.
      In order to start effective interventions for abused women, the appropriate
      method of screening for IPV in healthcare settings needs clarifying. The
      objective of this study was to compare the effectiveness of a face-to-face
      interview with a self-administered questionnaire. We used the Violence Against
      Women Screen (VAWS), a Japanese screening instrument for intimate partner
      violence (IPV), for identifying pregnant women who have experienced abuse.
      METHODS: We conducted a randomised controlled trial to screen participants at
      three points in time in a prenatal clinic in Tokyo, Japan. There were 328
      consenting women between 14 and 25 weeks of pregnancy who were consecutively
      selected and randomly assigned to either the interview or self-administered
      questionnaire group. Both groups completed the same screening instrument three
      times during their pregnancy. The primary outcome was the total number of women
      identified by each screening method and the secondary outcome was the effect of
      the screening as measured by the women's comfort level and their expressed need
      to consult with the nurse. RESULTS: For all three screenings, the identification
      rate in the interview group was significantly lower than that for the self
      administered questionnaire group (relative risk 0.66, 95% CI 0.46 to 0.97), even
      after controlling for smoking (adjusted odds ratio 0.59, 95% CI 0.35 to 0.98).
      The two groups did not differ for secondary outcomes. CONCLUSIONS: The self
      administered questionnaire identified more IPV than the face-to-face interview
      when screening pregnant women in a Japanese prenatal clinic. TRIAL REGISTRATION:
      UMIN-CTRC000000353.

PMID- 21182801
TI  - Beta-estradiol attenuates hypoxic pulmonary hypertension by stabilizing the
      expression of p27kip1 in rats.
AB  - BACKGROUND: Pulmonary vascular structure remodeling (PVSR) is a hallmark of
      pulmonary hypertension. P27(kip1), one of critical cyclin-dependent kinase
      inhibitors, has been shown to mediate anti-proliferation effects on various
      vascular cells. Beta-estradiol (beta-E2) has numerous biological protective
      effects including attenuation of hypoxic pulmonary hypertension (HPH). In the
      present study, we employed beta-E2 to investigate the roles of p27(kip1) and its
      closely-related kinase (Skp-2) in the progression of PVSR and HPH. METHODS:
      Sprague-Dawley rats treated with or without beta-E2 were challenged by
      intermittent chronic hypoxia exposure for 4 weeks to establish hypoxic pulmonary
      hypertension models, which resemble moderate severity of hypoxia-induced PH in
      humans. Subsequently, hemodynamic and pulmonary pathomorphology data were
      gathered. Additionally, pulmonary artery smooth muscle cells (PASMCs) were
      cultured to determine the anti-proliferation effect of beta-E2 under hypoxia
      exposure. Western blotting or reverse transcriptional polymerase chain reaction
      (RT-PCR) were adopted to test p27(kip1), Skp-2 and Akt-P changes in rat lung
      tissue and cultured PASMCs. RESULTS: Chronic hypoxia significantly increased
      right ventricular systolic pressures (RVSP), weight of right ventricle/left
      ventricle plus septum (RV/LV+S) ratio, medial width of pulmonary arterioles,
      accompanied with decreased expression of p27(kip1) in rats. Whereas, beta-E2
      treatment repressed the elevation of RVSP, RV/LV+S, attenuated the PVSR of
      pulmonary arterioles induced by chronic hypoxia, and stabilized the expression of
      p27(kip1). Study also showed that beta-E2 application suppressed the
      proliferation of PASMCs and elevated the expression of p27(kip1) under hypoxia
      exposure. In addition, experiments both in vivo and in vitro consistently
      indicated an escalation of Skp-2 and phosphorylated Akt under hypoxia condition.
      Besides, all these changes were alleviated in the presence of beta-E2.
      CONCLUSIONS: Our results suggest that beta-E2 can effectively attenuate PVSR and
      HPH. The underlying mechanism may partially be through the increased p27(kip1) by
      inhibiting Skp-2 through Akt signal pathway. Therefore, targeting up-regulation
      of p27(kip1) or down-regulation of Skp-2 might provide new strategies for
      treatment of HPH.

PMID- 21182803
TI  - Effect of postpartum lifestyle interventions on weight loss, smoking cessation,
      and prevention of smoking relapse: a systematic review.
AB  - Postpartum lifestyle interventions are recommended for women after pregnancies
      complicated by preeclampsia, intrauterine growth restriction, and/or gestational
      diabetes, since they are at increased cardiovascular risk. To identify potential
      intervention strategies to reduce this risk, a systematic review of the
      literature is presented on the effectiveness of postpartum lifestyle
      interventions aimed at weight loss, smoking cessation, and smoking relapse
      prevention. The main characteristics of these postpartum lifestyle interventions
      are briefly described. The PubMed, Embase, Web of Science, PsychInfo, and Cinahl
      databases were searched for studies on the effects of postpartum lifestyle
      interventions on weight loss, and smoking cessation or prevention of smoking
      relapse, initiated for up to 1 year postpartum. No studies on the effectiveness
      of postpartum lifestyle interventions after the aforementioned specific pregnancy
      complications were found. However, 21 studies are included that describe existing
      postpartum lifestyle interventions, which were applied to unselected (on the
      basis of pregnancy complications) postpartum women. Six of 8 weight loss
      interventions, 4 of 5 smoking cessation interventions, and 4 of 8 smoking relapse
      prevention interventions were effective. Individually tailored counseling, group
      counseling sessions, and use of diaries or other correspondence materials were
      shown to be effective. Currently, postpartum lifestyle interventions tailored
      specifically for women who experienced the pregnancy complications are lacking.
      While awaiting their development, it seems reasonable to utilize existing
      lifestyle interventions shown to be effective in unselected postpartum women.
      LEARNING OBJECTIVES: After completion of this educational activity, the
      obstetrician/gynecologist should be better able to: counsel patients on how to
      apply existing postpartum lifestyle intervention strategies aimed at weight loss,
      smoking cessation, and smoking relapse prevention to lower future cardiovascular
      risk; and educate postpartum women who have experienced preeclampsia, intra
      uterine growth restriction, and/or gestational diabetes about their increased
      cardiovascular risk later in life. TARGET AUDIENCE: Obstetricians &
      Gynecologists, Family Physicians.

PMID- 21182804
TI  - Combined vitamin C and E supplementation for the prevention of preeclampsia: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To perform a systematic review and meta-analysis of the effectiveness
      of combined vitamin C and E (vitCE) supplementation for the prevention of
      preeclampsia. DATA SOURCES: PubMED, Web of Science, and Cochrane Central Register
      of Controlled Trials from inception through June 2010, and bibliographies of
      review articles and eligible studies. METHODS OF STUDY SELECTION: Fifteen
      eligible studies that evaluated vitCE supplementation for the prevention of
      preeclampsia were identified. On the basis of prespecified inclusion and
      exclusion criteria, 9 were included in the meta-analysis. All were randomized
      controlled trials. The reporting and methodologic quality of the included studies
      was assessed with the CONSORT checklist and the Jadad scale. TABULATION,
      INTEGRATION, AND RESULTS: The 9 included studies had moderate-to-high CONSORT and
      Jadad scores. The incidence of preeclampsia was 9.7% (949 of 9833) in the vitCE
      group and 9.5% (946 of 9842) in the placebo group. A random effects model was
      used for pooling and no difference was found in the relative risk (RR) of
      preeclampsia between the vitCE and placebo groups (RR: 0.98; 95% confidence
      interval [CI]: 0.87-1.10). The incidence of gestational hypertension was 22.6%
      (1915 of 8491) in the vitCE group and 20.3% (1728 of 8500) in the placebo group
      (RR: 1.11, 95% CI: 1.05-1.17). The incidence of placental abruption was 0.58% (43
      of 7379) in the vitCE group and 0.87% (64 of 7361) in the placebo group (RR:
      0.67, 95% CI: 0.46-0.98). No significant differences were observed for other
      maternal and neonatal outcomes. CONCLUSION: Combined VitCE supplementation does
      not decrease the risk of preeclampsia and should not be offered to gravidas for
      the prevention of preeclampsia or other pregnancy induced hypertensive disorders.
      Furthermore, combined supplementation with vitCE increased the risk of GH but
      decreased the risk of placental abruption. However, these latter associations may
      not be causal, especially since they were the product of multiple statistical
      comparisons, and the 95% CI around the point estimates almost included one.
      LEARNING OBJECTIVES: After completion of this educational activity, the
      obstetrician/gynecologist should be better able to assess the causes of
      preeclampsia and related conditions; evaluate and interpret the evidence
      regarding the use of combined vitamins C and E in prevention of preeclampsia and
      related conditions; and interpret and understand the effects of the
      supplementation of vitamins C and E for the prevention of preeclampsia or other
      pregnancy induced hypertensive disorders. TARGET AUDIENCE: Obstetricians &
      Gynecologists, Family Physicians.

PMID- 21182805
TI  - Gynecologic care in hematopoietic stem cell transplant patients: a review.
AB  - Over 4500 hematopoietic stem cell transplants (HSCT) are performed on patients in
      the United States each year. As HSCT patients shift their survivorship care from
      large transplant centers to community health care providers, many gynecologists
      are assuming their pre- and post-HSCT gynecologic care. This article reviews
      recommendations, current research, and expert opinions on the gynecologic care of
      HSCT patients. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians.
      LEARNING OBJECTIVES: After completing this educational activity, the physician
      should be better able to implement strategies for the prevention and management
      of menstrual bleeding during hematopoietic stem cell transplants; educate female
      patients regarding Fertility Preservation options before hematopoietic stem cell
      transplantation; and apply posthematopoietic stem cell transplant reproductive
      care screening and treatment recommendations for bone health, sexual health, and
      secondary cancer development.

PMID- 21182806
TI  - [Relationship between chemosensitivity in vitro and the expression of GRP78 in
      non-small cell lung cancer].
AB  - BACKGROUND: The expressive level of glucose-regulated protein 78 (GRP78) is
      elevated and correlated with resistance of chemotherapy drugs in breast cancer
      cell. However, little is known about the relationship between its expression and
      drug resistance in non-small cell lung cancer (NSCLC). The aim of this study was
      to explore the relationship between drug resistance and the expression of GRP78
      in NSCLC. METHODS: Drug sensitivity test was used to detect the resistance to 8
      chemotherapy drugs in 52 NSCLC fresh surgical samples by methylthiazoletrazolium
      (MTT), and expression of GRP78 was detected by immunohistochemistry method.
      Spearman correlation assay was used to investigate the correlation between the
      GRP78 expression and drug resistance. RESULTS: The resistance rates to paclitaxel
      (PTX), adriamycin (ADM), carboplatin (CBP), topotecan (TPT), navelbine (NVB),
      vincristine (VCR), cisplatin (DDP) and etoposide (VP-16) of the 52 samples were
      42.31%, 57.69%, 63.46%, 65.38%, 67.31%, 73.08%, 78.85%, 90.38%, respectively.
      Fourteen cases showed the complete resistance to the total 8 chemotherapy drugs.
      Furthermore, the expression of GRP78 was stronger in poorly differentiated cancer
      as compared with the well and moderately differentiated cancer (P < 0.05), so as
      in stage II and III cancer than in stage I cancer (P < 0.05). Spearman
      correlation assay showed that there was a correlation between the
      chemotherapeutics resistance to ADM, VP-16, VCR, TPT and the expression of GRP78
      in NSCLC (P < 0.05). CONCLUSIONS: It is feasible to detect the drug sensitivity
      to chemotherapy for tumor cells by MTT method. The results of chemosensitivity
      assay in vitro are indicative of clinical drug administration in NSCLC. The
      detection of GRP78 isalso indicative of the resistance to chemotherapy drugs and
      the differentiation and the clinical stage in NSCLC.

PMID- 21182807
TI  - [Inhibitory effect of Periplaneta Americana extract on 3LL lung cancer in mice].
AB  - BACKGROUND: It has been known that Kangfuxin, a drug derived from Periplaneta
      Americana, can induce cell apoptosis of many cancer cell lines in vitro. The aim
      of this study is to investigate the inhibitory effect and mechanism of
      Periplaneta Americana extract (PAE) on 3LL lung cancer in mice. METHODS: The
      C57BL/6J mice transplanted with 3LL lung cancer were divided into normal saline
      (NS), PAE high dose (PAE-H) and PAE low dose (PAE-L) groups. The body weight
      changes and inhibitory rate of tumor growth in each group were observed. In
      addition, the cell cycle, apoptosis index (AI) and the expression of apoptosis
      associated genes were analysed by flow cytometry (FCM). RESULTS: The body weights
      were decreased in PAE-L and PAE-H treated group compared with NS group and the
      inhibitive rate of tumor growth was 41.24% and 81.08% respectively. FCM assay
      indicated that PAE could induce apoptosis of lung cancer cell, and the apoptosis
      rate was concentration-dependent. At the same time, the number of S and G2/M
      phase cells was decreased, most of the cells were arrested in G1/G1 phase. The
      result of TUNEL showed that there were apoptosis and necrosis associated with
      upregulated expression of Fas, FasR and p53 genes, and downregulated expression
      of Bcl-2. CONCLUSIONS: PAE may inhibit the growth of 3LL lung cancer in mice and
      induce apoptosis of 3LL lung cancer cells. It might be related to its effects on
      the regulation of apoptotic gene expression.

PMID- 21182808
TI  - [Association of genetic polymorphism in the DNA repair gene XPD with risk of lung
      cancer in nonsmoking females].
AB  - BACKGROUND: Xeroderma pigmentosum group D (XPD) is one of the important DNA
      repair genes. XPD polymorphism at Lys751Gln site has been shown to alter XPD
      protein function, modulate DNA repair capacity and therefore affect cancer risk.
      The aim of this study is to explore the relationship between XPD polymorphism and
      susceptibility to lung cancer in nonsmoking female via a population-based case
      control study. METHODS: There were 105 female patients who were diagnosed with
      lung cancer between January 2004 and December 2005 from Liaoning Tumor Hospital
      and 202 Hospital, and the control group included 105 healthy volunteers who were
      obtained from community centers at the same time. Information concerning
      demographic and risk factors was obtained for each case and control by a trained
      interviewer. XPD genotypes of cases and controls were determined by PCR-RFLP
      method. Two-sided Chi-Square test was used to compare the distribution of the
      genotypes and risk factors between cases and controls. Unconditional logistic
      regression analysis was performed to calculate the odds ratios (OR) with 95%
      confidence intervals (CI) for estimating the association between certain
      genotypes and lung cancer and exploring the interaction of environmental risk
      factors and genetic polymorphism. RESULTS: All of the subjects in this study were
      nonsmoking females in Shenyang. There was no significant demographic difference
      (age, economic level and education) between cases and controls. There was a
      significant difference in the frequencies of XPD polymorphism between cancer
      cases and controls. The frequencies of XPD 751Gln allele were 6.2% in controls
      and 13.8% in cases (P < 0.05). The risk of lung cancer was higher in those with
      the Lys/Gln or Gln/Gln genotype than in those with the Lys/Lys genotype and
      adjusted OR was 2.80 (95% CI: 1.21-6.48). The result showed that cooking fumes
      exposure was a risk factor for lung cancer (OR was 2.44). Furthermore, an
      interaction between environmental risk factors and the variant XPD 751Gln allele
      on the risk of lung cancer was observed. Individuals with both risk gen-otype and
      exposure to cooking fumes had a higher elevated risk of cancer than those with
      only one of them (adjusted OR= 6.85 ; 95% CI: 1.69-27.67; P=0.007). CONCLUSIONS:
      The above findings indicate that the Lys751Gln polymorphism in XPD gene is
      associated with the risk of lung cancer in nonsmoking females. Individuals with
      both XPD 751Gln allele genotype and exposure to cooking fumes have a higher
      elevated risk of cancer than those with only one of them in nonsmoking female
      population.

PMID- 21182809
TI  - [A case-control study on the impact of cytochrome P450 2E1 and 1A1 gene
      polymorphisms on the risk of lung can- cer of the Han nationality in Guangzhou
      district].
AB  - BACKGROUND: Most of the researches about lung cancer have focused on the
      polymorphisms of single gene rather than the cooperation of the genes. The aim of
      this study is to investigate the correlation of gene polymorphisms of cytochrome
      P450 2E1 (CYP2E1) Rsa I and cytochrome P450 1A1 (CYP1A1) independently and in
      combination with the risk of lung cancer. METHODS: A case-control study which
      included 91 lung cancer cases and 91 hospital-based controls was carried out, and
      all of them were the Han nationality in Guangzhou district. Blood samples were
      collected for detecting CYP2E1 Rsa I and CYP1A1 gene polymorphisms by polymerase
      chain reaction (PCR) and restriction fragment length polymorphisms (RFLP).
      RESULTS: No significant difference was observed in genotype frequencies of CYP2E1
      Rsa I and CYP1A1 Msp I between case and control groups. Odd ratio was 5.48 and
      1.51 respectively without significant difference (P > 0.05). Individuals with
      CYP2E1 Rsa I C1C1 and CYP1A1 m2m2 genotype had 3.00-fold risk of developing lung
      cancer compared with those who had CYP2E1 Rsa I C1C2 and CYP1A1 m1m1 genotype (P
      < 0.05, 95% CI 1.03-8.78). CONCLUSIONS: Single polymorphism of CYP2E1 and CYP1A1
      doesn't increase the risk of developing lung cancer, but the combination of two
      genetic polymorphisms significantly increases the risk of developing lung cancer.

PMID- 21182810
TI  - [Clinical significance and expression of fatty acid synthase mRNA in lung
      cancer].
AB  - BACKGROUND: Fatty acid synthase (FAS) is differentially overexpressed and
      hyperactivated in many tumors and indicates poor prognosis. The aim of this study
      is to explore the expression of FAS mRNA and its significance in lung cancer
      tissues and paracancerous tissues, compared with normal lung tissues. METHODS:
      Fifty-five lung cancer tissues, 32 paracancerous tissues and 32 normal lung
      tissues were collected. Reverse transcription polymerase chain reaction (RT-PCR)
      and imaging analysis were applied to determine the FAS mRNA expression. RESULTS:
      The positive rate of FAS mRNA expression was 72.7%, 62.5% and 25.0% in lung
      cancer tissues, paracancerous tissues and normal lung tissues, respectively (P <
      0.01). The expression level of FAS mRNA was 0.885+/-0.06 in lung cancer tissues,
      0.564+/-0.10 in paracancerous tissues and 0.259+/-0.04 in normal lung tissues.
      The expression level of FAS mRNA in lung cancer was significantly higher than
      that in paracancerous tissues and normal lung tissues (P < 0.01). CONCLUSIONS:
      FAS mRNA is significantly overexpressed in lung cancer. The results suggest that
      overexpression of tumor lipid metabolism may play an important role in the
      oncogenesis and development of lung cancer.

PMID- 21182811
TI  - [Feasibility and its clinical significance of detection of LUNX mRNA expression
      in diagnosis of micrometastasis for non-small cell lung cancer].
AB  - BACKGROUND: There is important significance of micrometastasis for the individual
      treatment and prognosis of non-small cell lung cancer (NSCLC). LUNX is a lung
      specific gene found recently. The aim of this study is to detect LUNX mRNA
      expression in NSCLC patients in order to discuss the possibility of indicating
      lung cancer micrometastasis by LUNX. METHODS: Fluorescence quantitative reverse
      transcription-polymerase chain reaction (FQ-RT-PCR) and ordinary RT-PCR were used
      to detect LUNX mRNA in cancer tissues, bone marrow and peripheral blood from 62
      patients with NSCLC. Lung tissue, bone marrow and peripheral blood from 10
      patients with pulmonary benign diseases and peripheral blood from 10 healthy
      volunteers were served as controls. RESULTS: LUNX mRNA was expressed in all the
      lung tissues, either malignant or benign. No bone marrow and peripheral blood
      sample was positive for LUNX mRNA in controls. The positive detection rate of
      LUNX mRNA for NSCLC was 38.7% (24/62) in bone marrow, 29.0% (18/62) in peripheral
      blood, and 45.2% (28/62) in either. The positive rate of LUNX mRNA for NSCLC in
      bone marrow increased according to the stage of disease and there was a
      statistical significance (P=0.02), aod there was a correlation between bone
      marrow and peripheral blood expression in NSCLC (P < 0.001). CONCLUSIONS: LUNX
      mRNA is an efficient indicating factor on sensitivity and specificity to detect
      early haematogenous dissemination of cancer cells for patients with NSCLC. This
      method may lead to an earlier diagnosis of metastasis for lung cancer and help to
      evaluate the cancer more correctly and make the best treatment plan.

PMID- 21182812
TI  - [Expression of vascular endothelial growth factor (VEGF) and its receptors KDR,
      Flt1 in lung cancer and their relationship to prognosis].
AB  - BACKGROUND: It is well known that vascular endothelial growth factor (VEGF) and
      its receptors are closely related to tumor angiogenesis, but the exact
      relationship with patients' prognosis is unclear till now. The aim of this study
      is to explore the expression of VEGF and its receptors KDR, Flt1 in pulmonary
      carcinoma and their relationship with patients' prognosis. METHODS: The
      expression of VEGF, KDR and Flt1 was examined immunohistochemically by PV-9000
      method in 75 cases of pulmonary carcinoma with complete follow-up records.
      RESULTS: There was an extensive expression of VEGF, KDR and Flt1, mainly in the
      cytoplasm of tumor cells (TCs), fibroblasts (FBs), and endothelial cells. The
      distribution of VEGF, KDR and Flt1 was heterogeneous, mainly located at periphery
      of the tumor mass or necrosis. The positive rate of VEGF, KDR and Flt1 in the TCs
      was all significantly higher than that in the FBs (P < 0.01, P < 0.02, P < 0.02).
      Both in TCs and FBs, the positive expression of VEGF, KDR and Flt1 was related to
      the postoperative survival of patients (P < 0.01, P < 0.01, P < 0.01; P < 0.01, P
      < 0.01, P < 0.05). The survival time in patients with positive VEGF, KDR or Flt-1
      in TCs was significantly lower than that in those with corresponding negative one
      respectively (P < 0.0001, P < 0.0005, P < 0.0005). There was a positive
      correlation between VEGF and Flt1 in TCs (P < 0.01), between VEGF in FBs and Flt1
      in TCs (P < 0.01), and also between VEGF and KDR or Flt1 in FBs (P < 0.01, P <
      0.01). CONCLUSIONS: VEGF may act as a considerable promoting growth factor on
      tumor cells via Flt1, mainly in autocrine and less in paracrine manner. VEGF, KDR
      and Flt1 may exert important roles in prognosis of patients with pulmonary
      carcinoma.

PMID- 21182813
TI  - [Relationship between expression of VEGF-C and lymph node metastasis in human non
      small cell lung cancer].
AB  - BACKGROUND: It has been showed that VEGF-C can induce the proliferation of
      lymphocytes. The aim of this study is to explore the expression of VEGF-C in
      human non-small cell lung can-cer (NSCLC) and its relationship with lymph node
      metastasis. METHODS: The expression of VEGF-C was examined in 60 human NSCLC
      tissues by immunohistochemical technique.. RESULTS: The positive rate of VEGF-C
      expression was 65.00% (39/60) in NSCLC tissues. The expression of VEGF-C was
      significantly higher in cases with lymph node metastasis (83.33%, 20/24) than in
      those without lymph node metastasis (52.78%, 19/36) (P < 0.05). CONCLUSIONS:
      There is an overexpression of VEGF-C protein in human NSCLC tissues, which may
      correlate with lymph node metastasis. The expression of VEGF-C protein might be
      used as a useful mar- ker of lymph node metastasis in NSCLC.

PMID- 21182814
TI  - [Genetic polymorphisms in methylenetetrahydrofolate reductase and clinical
      response to chemotherapy in non-small cell lung cancer].
AB  - BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) plays an important role
      in metabolism of folate and DNA methylation. In vitro, many studies have
      demonstrated that abnormal methylation of some genes may affect the sensitivity
      of tumor cells to cytotoxic drugs and agents interfering with DNA synthesis. The
      aim of this study is to investigate the relationship between genetic
      polymorphisms of MTHFR C677T or A1298C and the response to platinum-based
      chemotherapy in non-small cell lung cancer (NSCLC). METHODS: A total of 97
      patients with NSCLC were analyzed. MTHFR genotypes were detected in all the
      patients by PCR-RFLP method. All the patients were treated with platinum-based
      chemotherapy. RESULTS: (1) Out of all the cases, the frequencies of MTHFR C677T
      C/C, C/T and T/T genotypes were 34.0%, 50.5% and 15.5%, respectively, while the
      frequencies of MTHFR A1298C A/A, A/C and C/C genotypes were 64.6%, 29.2% and
      6.3%, respectively. The overall response rate (complete and partial response) to
      platinum-based chemotherapy was 39.2%. (2) No significant difference in response
      rate to chemotherapy was observed according to the MTHFR C677T or A1298C
      genotypes. However, MTHFR C677T and A1298C polymorphisms showed a synergic effect
      on chemotherapeutic efficacy, the response rate of patients with MTHFR C677T T
      allele and A1298C A/A genotype (51.1%) was significantly higher than those with
      MTHFR C677T C/T and A1298C C allele (12.5%)(P=0.007, OR=7.30, 95% CI: 1.34
      52.47). CONCLUSIONS: The results suggest that the synergic effect between MTHFR
      C677T and A1298C polymorphisms is associated with clinical response to platinum
      based chemotherapy. Detection of MTHFR genotypes may indicate the sensitivity of
      NSCLC patients to platinum-based chemotherapy.

PMID- 21182815
TI  - [Multivariate analysis of prognostic factors in patients with small cell lung
      cancer].
AB  - BACKGROUND: Multimodality treatment is the milestone of improving the prognosis
      of patients with small cell lung cancer (SCLC). The aim of this study is to
      retrospectively review the prognostic factors for SCLC. METHODS: From January
      1999 to June 2005, clinical data were collected from 253 patients who had a good
      performance status (PS=0-1) and underwent multimodality therapy
      (chemotherapy+radiotherapy+/-surgery), and the prognostic factors were analyzed
      by Kaplan-Meier and COX multivariate proportional hazards model. RESULTS: With a
      median follow-up of 23.2 months (3-85 months), 1-, 3-, and 5-year survival rate
      was 77.9%, 33.8% and 23.3% respectively, and 88.3%, 40.2%, 31.2% in LD patients,
      62.9%, 22.0% and 8.8% in ED patients, respectively. Median survival time (MST) of
      all the patients was 23 months (95% CI: 19-27 months). Univariate analysis
      indicated that gender (P=0.0395), stage (P= 0.0000 ), LDH (P=0.0000), operation
      (P=0.0029), weight loss (P=0.0000) and the efficacy of first-line chemotherapy
      (P=0.0000) significantly influenced survival in SCLC. Multivariate analysis
      suggested that gender (P=0.019), LDH (P=0.000), operation (P=0.024) and weight
      loss (P=0.006) were the independent prognostic factors of survival. CONCLUSIONS:
      Gender, LDH, operation, and weight loss are the important prognostic factors for
      patients with SCLC who have a good PS and undergo multimodality treatment.

PMID- 21182816
TI  - [Prognostic analysis of intrapulmonary metastasis for patients with non-small
      cell lung cancer].
AB  - BACKGROUND: It is well known that more than 40% patients were initially diagnosed
      with advanced non-small cell lung cancer (NSCLC) with intrapulmonary or/and
      distant metastasis. However, up to now, the reports about effects of different
      metastatic sites on survival were limited. The aim of this study is to
      investigate the clinicopathologic and survival difference by retrospective
      analysis among sole intrapulmonary metastasis, sole extrathoracic distant
      metastasis and simultaneous metastasis of lung and other extrathoracic organs for
      the patients with advanced NSCLC, and to analyze the prognosis-related factors of
      NSCLC with intrapulmonary metastasis. METHODS: Of the 425 patients with stage IV
      NSCLC diagnosed by pathology and through staging evaluation and treated at
      Beijing Cancer Hospital with long follow-up during Oct. 1995 to Dec. 2003, 81
      cases had sole intrapulmonary metastasis, 98 cases had sole extrathoracic distant
      metastasis and 68 cases presented simultaneous lung metastasis and extrathoracic
      spread. Kaplan-Meier survival curve was performed to estimate the survival of
      patients with different metastasis, Log-Rank test was used to compare their
      survival difference, and univariate analysis was used to find prognostic related
      factors. RESULTS: Median survival time (MST) and 1-, 2-, 3-year survival rate
      (SR) for patients with sole intrapulmonary metastasis were 13 months (95% CI: 11
      15), 57%, 21%, 7%, respectively; MST was 22 months (95% CI: 18-26) for patients
      with N1 and/or N2 and 10 months (95%CI: 7-13) for patients with N3 (P=0.001).
      Among the patients with ipsilateral, contralateral and bilateral intrapulmonary
      metastasis, difference of MST and 1-, 2-, 3-year SR had no statistical
      significance (P > 0.05); Survival of patients with sole intrapulmonary metastasis
      was not significantly different from that of patients with sole brain or bone
      metastasis (P > 0.05), but was longer than that of patients with simultaneous
      lung and extrathoracic spread (P=0.021). One way analysis of variance showed that
      no significant association were found among age, pathologic subtype,
      differentiation degree or response of first-line chemotherapy and survival of the
      patients with sole intrapulmonary metastasis (P > 0.05), but sex and invasive
      status of lymph node (N1/N2 vs N3) were found to influence the survival of the
      patients (P= 0.018, P=0.001). Further stratified analysis by age showed that
      invasion of lymph node was independent prognostic factor (P=0.002); whereas for
      the patients with simultaneous metastasis of lung and distant organs, metastatic
      numbers (2 vs >=3) of organ were independent prognostic factor (P=0.013).
      CONCLUSIONS: No statistical difference is found among survival of NSCLC patients
      with sole intrapulmonary metastasis and with sole brain, bone metastasis.
      Invasive status of lymph node and metastatic number of organ are important
      prognostic factors for patients with sole intrapulmonary metastasis and
      simultaneous metastasis of lung and extrathoracic organs, respectively.

PMID- 21182817
TI  - [A randomized clinical trial of Uroacitides combined with NP and NP regimen alone
      for advanced non-small cell lung cancer].
AB  - BACKGROUND: Uroacitides is a group of cell differentiation inducers, which is
      purified from fresh human urine. Preclinical studies of Uroacitides have showed
      that cancer cells could be induced to differentiate, and the growth of cancer
      cells could be inhibited by Uroacitides. The aim of this study is to compare the
      efficacy and toxicity between Uroacitides combined with NP regimen and NP alone
      in treatment of advanced non-small cell lung cancer (NSCLC). METHODS: Forty-two
      cases of advanced NSCLC were randomized into Uroacitides+NP and NP groups. NP
      group: NVB 25mg/m2 on days 1 and 8, DDP 75mg/m2 on day 1. Uroacitides combined
      with NP group: Uroacitides of 300mL was given through subclavian catheter daily
      for 7 days prior to the NP chemotherapy, then concurrently with NP regimen for 2
      cycles, except the days of administration of chemotherapy. RESULTS: In the
      Uroacitides+NP group, the overall response rate was 44.4%, and 20.0% in the NP
      group (P > 0.05). The median survival time was 9 months in the Uroacitides+NP
      group and 6 months in the NP group (P=0.0287). The main toxicities were
      myelosuppression, gastrointestinal reaction and alopecia, and there was no
      significant difference in incidences of toxicities between the two groups (P >
      0.05). CONCLUSIONS: Uroacitides combined with NP regimen shows a good curative
      effect and low toxicity, and may significantly prolong the median survival time
      for advanced NSCLC.

PMID- 21182818
TI  - [Treatment and prognosis of brain metastases from non-small cell lung cancer: A
      retrospective study].
AB  - BACKGROUND: Now the treatment of non-small cell lung cancer (NSCLC) patients with
      brain metastasis is not a standard program. The aim of this study is to summarize
      the factors related to survival of patients with brain metastases from NSCLC.
      METHODS: A total of 111 NSCLC patients with brain metastases (from September 1995
      May 2004) were defined as symptomatic group (37 patients) and asymptomatic group
      (74 patients) according to central nervous system (CNS) symptoms. The patients in
      the symptomatic group were given whole brain radiation therapy (WBRT, DT 30
      40Gy/20f) first, and then received cisplatin-based chemotherapy. The patients in
      the asymptomatic group were given cisplatin-based chemotherapy first, and then
      received WBRT. During the treatment, 49 patients received chemotherapy of BCNU or
      VM-26 irregularly. RESULTS: The median survival time was 11 months. The 1-and 2
      year survival rate was 40.79% and 13.26% respectively. The survival time was not
      significantly different between the symptomatic group and asymptomatic group.
      Median chemotherapy of asymptomatic group was 3 cycles (1-6 cycles) before WBRT.
      Those patients who received 3 or 4 cycles of chemotherapy before WBRT had better
      survival (P= 0.0188 , P=0.0035). The treatment of BCNU or VM-26 was a benefit
      factor for survival (P=0.0219) in asymptomatic group. The hematologic toxicity of
      grade III or IV was not significantly different between the two groups (P >
      0.05). The number of brain metastasis (P=0.000), extracranial metastasis
      (P=0.022) and WHO performance status (P=0.001) were independent prognostic
      factors. CONCLUSIONS: The patients with asymptomatic brain metastases receive 3-4
      cycles of chemotherapy before WBRT may be reasonable. During the therapy, the
      patients with administration of BCNU or VM-26 may have survival benefit.

PMID- 21182819
TI  - [Study on the value of cytopathology in diagnosis of primary bronchogenic
      carcinoma of the lung].
AB  - BACKGROUND: Pathology is the "gold standard" of the diagnosis of lung cancer, but
      at present there are few articles about evaluating the value of cytopathological
      check. The aim of this study is to evaluate the value of cytopathological check
      in the diagnosis of primary bronchogenic carcinoma of the lung. METHODS: A total
      of 552 samples' cytopathological results of 248 patients from January 2003 to May
      2005 in this hospital were retrospectively analyzed. The samples included pleural
      fluids (110 for 68 patients), materials from lung puncture (33 for 31 patients),
      smears of transcatheter bronchial brushing (152 for 138 patients),
      bronchoalveolar lavage fluids (30 for 26 patients) and sputa (227 for 118
      patients). RESULTS: The positive results of different specimens were as follow:
      the pleural fluids was 69.12%, the materials from lung puncture 67.74%, the
      smears of transcatheter bronchial brushing 65.22%, the bronchoalveolar lavage
      fluids 23.08% and sputa 21.19% respectively. The positive rates of the pleural
      fluids, the materials from lung puncture and the smears of transcatheter
      bronchial brushing were higher than that of the bronchoalveolar lavage fluids and
      sputa (P < 0.01). There was no significant difference among the positive rates of
      the pleural fluids, the materials from lung puncture and the smears of
      transcatheter bronchial brushing, and between the positive rates of the
      bronchoalveolar lavage fluids and sputa (P > 0.05). CONCLUSIONS: The
      cytopathological examination is helpful for the diagnosis of primary bronchogenic
      carcinoma of the lung, and is one of the important ways to the diagnosis of
      primary bronchogenic carcinoma of the lung.

PMID- 21182820
TI  - [Clinical analysis of sarcomatoid carcinoma of the lung].
AB  - BACKGROUND: Sarcomatoid carcinoma (SC) is a rare malignant cancer with mixed
      tumor and sarcomatoid tissues. The aim of this study is to investigate the
      clinical manifestations and pathological findings of sarcomatoid carcinoma of the
      lung. METHODS: Data including clinical manifestations, pathological findings,
      treatment were retrospectively analysed from fourteen patients with lung
      sarcomatoid carcinoma confirmed by pathology and follow-up was carried out.
      RESULTS: Mean age at onset was 62 years old and gender ratios (M/F) in these
      patients was 6:1. The clinical manifestations of lung sarcomatoid carcinoma were
      similar to that of other types of lung cancer while there were characteristic
      findings on the enhancement CT scan. Bronchofiberscopy was not a reliable
      examination for final diagnosis. Cells with endothelial phenotype could be
      detected by immunohistochemical method. CONCLUSIONS: The final diagnosis of this
      disease depends on histopathological observation, while the diagnosis may be
      missed among patients without surgical intervention. Immunohistochemical
      examination is helpful for diagnosis and differential diagnosis. The therapeutic
      strategy is coincident with that for non-small cell lung cancer.

PMID- 21182821
TI  - Immunomodulatory effects of eicosapentaenoic acid through induction of regulatory
      T cells.
AB  - Dietary intake of omega-3 polyunsaturated fatty acids (PUFAs) has been found to
      affect inflammation and metabolism, and many researchers have shown that omega-3
      PUFAs provide benefits in immunologic and metabolic disorders. These effects were
      assumed to result mainly from a modification in the production of inflammatory
      mediators and the suppression of inflammatory leukocytes. Among PUFAs,
      eicosapentaenoic acid (EPA), a component of fish oil, apparently has the most
      potent effect. Recently, much research has focused on regulatory T cells (Tregs)
      as controllers of immune responses not only to self-antigens but also to non-self
      antigens, including donor alloantigens. Therefore, induction of antigen-specific
      Tregs may be an attractive strategy for managing autoimmune diseases and
      transplant rejection. Peroxisome proliferator-activated receptor gamma
      (PPARgamma), a ligand-activated nuclear receptor that regulates lipid and glucose
      metabolism, can be activated by thiazolidinediones, fatty acids, and eicosanoids,
      including EPA. PPARgamma was recently found to have immunoregulatory effects, and
      a PPARgamma agonist inhibited immune responses in a rat model of autoimmune
      disease. Furthermore, in a murine model, one high dose of purified EPA given the
      day of transplantation induced marked prolongation of cardiac allograft survival
      in a dose-dependent manner. These findings suggest that EPA induced Tregs by
      means of a PPARgamma-dependent mechanism. This review describes the
      immunomodulatory effects of PUFAs, especially EPA, and summarizes recent research
      that may have implications for the development of therapies for autoimmune
      diseases and transplant rejection that are based on induction of Tregs.

PMID- 21182822
TI  - On the miscibility of cardiolipin with 1,2-diacyl phosphoglycerides: binary
      mixtures of dimyristoylphosphatidylethanolamine and tetramyristoylcardiolipin.
AB  - The thermotropic phase behavior and organization of model membranes composed of
      binary mixtures of the quadruple-chained, anionic phospholipid
      tetramyristoylcardiolipin (TMCL) with the double-chained zwitterionic
      phospholipid dimyristoylphosphatidylethanolamine (DMPE) were examined by a
      combination of differential scanning calorimetry (DSC) and Fourier-transform
      infrared (FTIR) spectroscopy. After equilibration at low temperature, DSC
      thermograms exhibited by binary mixtures of TMCL and DMPE containing < 80 mol
      DMPE exhibit a fairly energetic lower temperature endotherm and a highly
      energetic higher temperature endotherm. As the relative amount of TMCL in the
      mixture decreases, the temperature, enthalpy and cooperativity of the lower
      temperature endotherm also decreases and is not calorimetrically detectable when
      the TMCL content falls below 20 mol%. In contrast, the temperature of the higher
      temperature endotherm increases as the proportion of TMCL decreases, but the
      enthalpy and cooperativity both decrease and the transition endotherms become
      multimodal. The FTIR spectroscopic results indicate that the lower temperature
      endotherm corresponds to a lamellar crystalline (L(c)) to lamellar gel (L(beta))
      phase transition and that the higher temperature transition involves the
      conversion of the L(beta) phase to the lamellar liquid-crystalline (L(alpha))
      phase. Moreover, the FTIR spectroscopic signatures observed at temperatures below
      the onset of the L(c)/L(beta) phase transitions are consistent with the
      coexistence of structures akin to a TMCL-like L(c) phase and the L(beta) phase,
      and with the relative amount of the TMCL-like L(c) phase increasing progressively
      as the TMCL content of the mixture increases. These latter observations suggest
      that the TMCL and DMPE components of these mixtures are poorly miscible at
      temperatures below the L(beta)/L(alpha) phase transition temperature. Poor
      miscibility of these two components is also suggested by the complexity of the
      DSC thermograms observed at the L(beta)/L(alpha) phase transitions of these
      mixtures and with the complex relationship between their L(beta)/L(alpha) phase
      transition temperatures and the composition of the mixture. Overall, our data
      suggests that TMCL and DMPE may be intrinsically poorly miscible across a broad
      composition range, notwithstanding the homogeneity of the fatty acid chains of
      the two components and the modest (~10  degrees C) difference between their
      L(beta)/L(alpha) phase transition temperatures.

PMID- 21182823
TI  - The predominant role of IP3 type 1 receptors in activation of store-operated Ca2+
      entry in liver cells.
AB  - Physiologically, hormone induced release of Ca2+ from intracellular stores occurs
      in response to inositol 1,4,5-trisphosphate (IP3) binding to its receptors
      expressed on the membranes of intracellular organelles, mainly endoplasmic
      reticulum. These IP3 receptors act as channels, releasing Ca2+ into the
      cytoplasmic space where it is responsible for regulating a host of distinct
      cellular processes. The depletion of intracellular Ca2+ stores leads to
      activation of store-operated Ca2+ channels on the plasma membrane which
      replenishes lost Ca2+ and sustain Ca2+ signalling. There are three isoforms of
      IP3 receptor, each exhibiting distinctive properties, however, little is known
      about the role of each isoform in the activation of store-operated Ca2+ entry.
      Recent evidence suggest that at least in some cell types the endoplasmic
      reticulum is not a homogeneous Ca2+ store, and there might be a sub-compartment
      specifically linked to the activation of store-operated Ca2+ channels, and Ca2+
      release activated Ca2+ (CRAC) channel in particular. Furthermore, this sub
      compartment might express only certain types of IP3 receptor but not the others.
      Here we show that H4IIE liver cells express all three types of IP3 receptor, but
      only type 1 and to a lesser extent type 3, but not type 2, participate in the
      activation of CRAC current (I(CRAC)), while type 1 and type 2, but not type 3,
      participate in observed Ca2+ release in response to receptor stimulation.
      Presented results suggest that in H4IIE rat liver cells the sub-compartment of
      intracellular Ca2+ store linked to the activation of I(CRAC) predominantly
      expresses type 1 IP3 receptors.

PMID- 21182824
TI  - Fatty acid composition modulates sensitivity of Legionella pneumophila to
      warnericin RK, an antimicrobial peptide.
AB  - Warnericin RK is an antimicrobial peptide, produced by a Staphyloccocus warneri
      strain, described to be specifically active against Legionella, the pathogenic
      bacteria responsible for Legionnaires' disease. Warnericin RK is an amphiphilic
      alpha-helical peptide, which possesses a detergent-like mode of action. Two
      others peptides, delta-hemolysin I and II, produced by the same S. warneri
      strain, are highly similar to S. aureus delta-hemolysin and also display anti
      Legionella activity. It has been recently reported that S. aureus delta-hemolysin
      activity on vesicles is likewise related to phospholipid acyl-chain structure,
      such as chain length and saturation. As staphylococcal delta-hemolysins were
      highly similar, we thus hypothesized that fatty acid composition of Legionella's
      membrane might influence the sensitivity of the bacteria to warnericin RK.
      Relationship between sensitivity to the peptide and fatty acid composition was
      then followed in various conditions. Cells in stationary phase, which were
      already described as less resistant than cells in exponential phase, displayed
      higher amounts of branched-chain fatty acids (BCFA) and short chain fatty acids.
      An adapted strain, able to grow at a concentration 33 fold higher than minimal
      inhibitory concentration of the wild type (i.e. 1MUM), was isolated after
      repeated transfers of L. pneumophila in the presence of increased concentrations
      of warnericin RK. The amount of BCFA was significantly higher in the adapted
      strain than in the wild type strain. Also, a transcriptomic analysis of the wild
      type and adapted strains showed that two genes involved in fatty acid
      biosynthesis were repressed in the adapted strain. These genes encode enzymes
      involved in desaturation and elongation of fatty acids respectively. Their
      repression was in agreement with the decrease of unsaturated fatty acids and
      fatty acid chain length in the adapted strain. Conclusively, our results indicate
      that the increase of BCFA and the decrease of fatty acid chain length in membrane
      were correlated with the increase in resistance to warnericin RK. Therefore,
      fatty acid profile seems to play a critical role in the sensitivity of L.
      pneumophila to warnericin RK.

PMID- 21182826
TI  - O-GlcNAcylation increases non-amyloidogenic processing of the amyloid-beta
      precursor protein (APP).
AB  - The amyloid-beta precursor protein (APP) was shown to be O-GlcNAcylated 15 years
      ago, but the effect of this modification on APP processing and formation of the
      Alzheimer's disease associated amyloid-beta (Abeta) peptide has so far not been
      investigated. Here, we demonstrate with pharmacological tools or siRNA that O
      GlcNAcase and O-GlcNAc transferase regulate the level of O-GlcNAcylated APP. We
      also show that O-GlcNAcylation increases non-amyloidogenic alpha-secretase
      processing, resulting in increased levels of the neuroprotective sAPPalpha
      fragment and decreased Abeta secretion. Our results implicate O-GlcNAcylation as
      a potential therapeutic target for Alzheimer's disease.

PMID- 21182825
TI  - Manipulation of cell volume and membrane pore comparison following single cell
      permeabilization with 60- and 600-ns electric pulses.
AB  - Intense nanosecond-duration electric pulses (nsEP) open stable nanopores in the
      cell membrane, followed by cell volume changes due to water uptake or expulsion,
      as regulated by the osmolality balance of pore-impermeable solutes inside and
      outside the cell. The size of pores opened by either fifty 60-ns EP (~13 kV/cm)
      or five, 600-ns EP (~6 kV/cm) in GH3 cells was estimated by isoosmotic
      replacement of bath NaCl with polyethylene glycols and sugars. Such replacement
      reduced cell swelling or resulted in transient or sustained cell shrinking in
      response to EP. depending on the availability of pores permeable to the test
      solute. Unexpectedly, solute substitutions showed that for the same integral area
      of pores opened by 60- and 600-ns treatments (as estimated by cell volume
      changes), the pore sizes were similar. However, the 600-ns exposure triggered
      significantly higher cell uptake of propidium. We concluded that 600-ns EP opened
      a greater number of larger (propidium-permeable pores), but the fraction of the
      larger pores in the entire pore population was insufficient to contribute to cell
      volume changes. For both the 60- and 600-ns exposures, cell volume changes were
      determined by pores smaller than 0.9 nm in diameter; however, the diameter
      increased with increasing the nsEP intensity.

PMID- 21182827
TI  - NF-kappaB inhibition improves the sensitivity of human glioblastoma cells to 5
      aminolevulinic acid-based photodynamic therapy.
AB  - Glioblastoma constitute the most frequent and deadliest brain tumors of
      astrocytic origin. They are very resistant to all current therapies and are
      associated with a huge rate of recurrence. In most cases, this type of tumor is
      characterized by a constitutive activation of the nuclear factor-kappaB (NF
      kappaB). This factor is known to be a key regulator of various physiological
      processes such as inflammation, immune response, cell growth or apoptosis. In the
      present study, we explored the role of NF-kappaB activation in the sensitivity of
      human glioblastoma cells to a treatment by 5-aminolevulinic acid (5-ALA)-based
      photodynamic therapy (PDT). 5-ALA is a physiological compound widely used in PDT
      as well as in tumor photodetection (PDD). Our results show that inhibition of NF
      kappaB improves glioblastoma cell death in response to 5-ALA-PDT. We then studied
      the molecular mechanisms underlying the cell death induced by PDT combined or not
      with NF-kappaB inhibition. We found that apoptosis was induced by PDT but in an
      incomplete manner and that, unexpectedly, NF-kappaB inhibition reduced its level.
      Oppositely PDT mainly induces necrosis in glioblastoma cells and NF-kappaB is
      found to have anti-necrotic functions in this context. The autophagic flux was
      also enhanced as a result of 5-ALA-PDT and we demonstrate that stimulation of
      autophagy acts as a pro-survival mechanism confering protection against PDT
      mediated necrosis. These data point out that 5-ALA-PDT has an interesting
      potential as a mean to treat glioblastoma and that inhibition of NF-kappaB
      renders glioblastoma cells more sensitive to the treatment.

PMID- 21182828
TI  - Neuroprotective effects of icariin on corticosterone-induced apoptosis in primary
      cultured rat hippocampal neurons.
AB  - Neurons are damaged following prolonged exposure to high concentrations of
      corticosterone, particularly during chronic inflammatory and immune diseases. One
      of the main mechanisms underlying neuronal injury is apoptosis. In the present
      study the neuroprotective effects of icariin, an active natural ingredient from
      the Chinese plant Epimedium sagittatum maxim against corticosterone-induced
      apoptosis were examined in primary cultured rat hippocampal neuronal cells. Pre
      treatment of neuronal cells with icariin suppressed corticosterone-induced
      cytotoxicity in a dose-dependent manner. Terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate (dUTP) nick-end-labeling assay (TUNEL)
      labeling demonstrated that icariin significantly reduced TUNEL-positive cell
      numbers induced by exposure of cultured neurons to corticosterone. Moreover,
      icariin markedly inhibited corticosterone-induced mitochondrial dysfunction,
      including improved mitochondrial membrane potential and inhibition of caspase-3
      activation. Using western blot analysis, corticosterone activated p38MAPK,
      extracellular regulated kinase 1/2(ERK1/2) ,and c-jun N-terminal protein kinase
      1(JNK1) ,while icariin blocked p38 MAPK, but not JNK1 or ERK1/2. Pharmacological
      approaches showed that the activation of p38MAPK plays a critical role in
      corticosterone-induced mitochondrial dysfunction and apoptosis. Taken together,
      the present results suggest that the protective effects of icariin on apoptosis
      in hippocampal neuronal cells are potentially mediated through blockade of p38
      MAPK phosphorylation.

PMID- 21182830
TI  - Postconditioning in focal cerebral ischemia: role of the mitochondrial ATP
      dependent potassium channel.
AB  - INTRODUCTION: Ischemic postconditioning (IpostC) has been described in both heart
      and brain. The first aim of this study was to evaluate the effects of IpostC on
      brain infarct size and neurological function in the middle cerebral artery
      occlusion (MCAO) model. The second aim was to determine the involvement of the
      mitochondrial potassium ATP-dependent channel (mitoK(ATP)) opening and its
      capacity to improve mitochondrial dysfunction induced by ischemia-reperfusion.
      METHODS: Wistar rats were subjected to 60min MCAO followed by 24-h reperfusion.
      Postconditioning was performed by 3 cycles of 30-s occlusion-reperfusion at the
      onset of reperfusion. Three behavioral tests were performed following 24h of
      reperfusion. Involvement of mitoK(ATP) was determined by the modulation of IpostC
      effects by 5-hydroxydecanoate (5-HD) and diazoxide. Mitochondrial function after
      24h of reperfusion on isolated mitochondria was assessed through mitochondrial
      oxygen consumption, mitochondrial membrane potential and calcium retention
      capacity to evaluate impact of IpostC on mitochondrial permeability transition
      pore (MPTP) opening. RESULTS: IpostC resulted in a 40% decrease in infarct size
      and improved neurological outcome. These effects were lost when IpostC was
      delayed by 5min. The administration of diazoxide resulted in a 60% in infarct
      size. The beneficial effects of IpostC and diazoxide were blocked by 5-HD.
      Furthermore, 5-HD also blocked the inhibition of MPTP opening by IpostC and
      diazoxide. The hyperpolarization induced by ischemia-reperfusion was corrected by
      IpostC without any effect on oxidative phosphorylation. CONCLUSION: Our results
      confirm ischemic postconditioning-induced neuroprotection. They also support the
      involvement of mitoK(ATP) opening and its role in inhibiting the opening of MTPT
      induced by postconditioning.

PMID- 21182829
TI  - tPA contributes to impairment of ATP and Ca sensitive K channel mediated
      cerebrovasodilation after hypoxia/ischemia through upregulation of ERK MAPK.
AB  - The sole FDA approved treatment for acute stroke is tissue type plasminogen
      activator (tPA). However, tPA potentiates impairment of pial artery dilation in
      response to hypotension after hypoxia/ischemia (H/I) in pigs. ATP and Ca
      sensitive K channels (Katp and Kca) are important regulators of cerebrovascular
      tone and mediate cerebrovasodilation in response to hypotension. Mitogen
      activated protein kinase (MAPK), a family of at least 3 kinases, ERK, p38 and
      JNK, is upregulated after H/I, with the ERK isoform contributing to vasodilator
      impairment. This study examined the effect of H/I on Katp and Kca induced pial
      artery dilation and the roles of tPA and ERK during/after injury in piglets
      equipped with a closed cranial window. H/I blunted vasodilation induced by the
      Katp agonists cromakalim, calcitonin gene related peptide (CGRP) and the Kca
      agonist NS 1619; the effect of each was exacerbated by tPA. Pre- or post-injury
      treatment with EEIIMD, a hexapeptide derived from plasminogen activator-1, and
      ERK antagonist U 0126 prevented Katp and Kca channel agonist induced vasodilator
      impairment while the inactive analogue EEIIMR had no effect. ERK was upregulated
      after H/I, which was potentiated by tPA. These data indicate that H/I impairs K
      channel mediated cerebrovasodilation. tPA augments loss of K channel function
      after injury by upregulating ERK. These data suggest that thrombolytic therapy
      for treatment of CNS ischemic disorders can dysregulate cerebrohemodynamics by
      impairing cation-mediated control of cerebrovascular tone.

PMID- 21182831
TI  - Progestins as inhibitors of the human 20-ketosteroid reductases, AKR1C1 and
      AKR1C3.
AB  - The human aldo-keto reductases 1C1 and 1C3 (AKR1C1 and AKR1C3) are important 20
      ketosteroid reductases in pre-receptor regulation of progesterone action. Both
      AKR1C1 and AKR1C3 convert progesterone to the less potent metabolite 20alpha
      hydroxyprogesterone, although AKR1C1 has a higher catalytic efficiency than
      AKR1C3. Recently, we reported significant up-regulation of AKR1C1 and AKR1C3 in
      ovarian endometriosis, a complex estrogen-dependent disease. The typical
      characteristics of endometriosis are increased formation of estradiol, which
      stimulates proliferation of endometriotic tissue, and disturbed action of the
      protective progesterone. Although progestins have been used for treatment of
      endometriosis since the 1960s, their detailed mechanisms of action are still not
      completely understood. In the present study, we evaluated the potential
      inhibitory effects of progestins on the pre-receptor regulatory enzymes AKR1C1
      and AKR1C3. We examined the following progestins as inhibitors of progesterone
      reduction catalyzed by recombinant AKR1C1 and AKR1C3: progesterone derivatives
      (dydrogesterone, its metabolite, 20alpha-hydroxydydrogesterone; and
      medroxyprogesterone acetate), 19-nortestosterone derivatives (desogestrel,
      norethinodrone and levonorgestrel), and the androgen danazol. Dydrogesterone,
      medroxyprogesterone acetate, 20alpha-hydroxydydrogesterone and norethinodrone
      inhibited AKR1C1 and AKR1C3 with K(i) values of 1.9 MUM, 7.9 MUM, 20.8 MUM and
      48.0 MUM, and of 0.5 MUM, 1.4 MUM, 18.2 MUM and 6.6 MUM, respectively.
      Levonorgestrel and desogestrel preferentially inhibited AKR1C3 with K(i) values
      of 5.6MUM and 39.1MUM, respectively. Our data thus show that dydrogesterone,
      medroxyprogesterone acetate, 20alpha-hydroxydydrogesterone and norethinodrone
      inhibit AKR1C1 and AKR1C3 in vitro, although their physiological inhibitory
      effects still need to be evaluated further. Additionally, we investigated whether
      progestin dydrogesterone can be metabolized to its active 20alpha
      hydroxymetabolite by AKR1C1 and AKR1C3. AKR1C1 converted dydrogesterone with a
      high catalytic efficiency while AKR1C3 was less active, which suggests that in
      vivo dydrogesterone is metabolized mainly by AKR1C1. Docking simulations of
      dydrogesterone into AKR1C1 and AKR1C3 also support these experimental data.

PMID- 21182832
TI  - Expression of estrogen and progesterone receptors and estrogen metabolizing
      enzymes in different breast cancer cell lines.
AB  - Prolonged exposure to estrogens is a significant risk factor for the development
      of breast cancer. Estrogens exert carcinogenic effects by stimulating cell
      proliferation or through oxidative metabolism that forms DNA-damaging species. In
      the present study, we aimed to provide a better understanding of estrogen
      metabolism and actions in breast cancer, and to characterize model breast cancer
      cell lines. We determined the expression profiles of the genes for the estrogen
      and progesterone receptors, and for 18 estrogen-metabolizing enzymes in eight
      cell lines: MCF-7, MCF-10A, T47D, SKBR3, MDA-MB-231, MDA-MB-361, Hs-578T and Hs
      578Bst cells. Similar gene expression profiles of these receptors and enzymes for
      the formation of estradiol via the aromatase and sulfatase pathways were observed
      in the MCF-7 and T47D metastatic cell lines. The MDA-MB-361 cells expressed ESR1,
      ESR2 and PGR as well, but differed in expression of the estrogen-metabolizing
      enzymes. In the MDA-MB-231 and SKBR3 cells, all of these estrogen-forming enzymes
      were expressed, although the lack of ESR1 and the low levels of ESR2 expression
      suggested that the estrogens can only act via non-ER mediated pathways. In the
      non-tumorigenic MCF-10A cell line, the key enzymes of the aromatase pathway were
      not expressed, and the sulfatase pathway also had a marginal role. The comparison
      between gene expression profiles of the non-tumorigenic Hs-578Bst cells and the
      cancerous Hs-578T cells revealed that they can both form estrogens via the
      sulfatase pathway, while the aromatase pathway is less important in the Hs-578Bst
      cells. The Hs-578T cells showed low levels of ESR1, ESR2 and PGR expression,
      while only ESR1 and ESR2 expression was detected in the Hs-578Bst cells. Our data
      show that the cell lines examined provide the full range of model systems and
      should further be compared with the expression profiles of breast cancer
      specimens.

PMID- 21182833
TI  - Possible involvement of oxidative stress in potassium bromate-induced
      genotoxicity in human HepG2 cells.
AB  - Potassium bromate (KBrO(3), PB) is a by-product of ozone used as disinfectant in
      drinking water. And PB is also a widely used food additive. However, there is
      little known about its adverse effects, in particular those related to its
      genotoxicity in humans. The aim of this study was to investigate the genotoxic
      effects of PB and the underlying mechanisms, using human hepatoma cell line,
      HepG2. Exposure of the cells to PB caused a significant increase of DNA migration
      in single cell gel electrophoresis (SCGE) assay and micronuclei (MN) frequencies
      in micronucleus test (MNT) at all tested concentrations (1.56-12.5 mM and 0.12-1
      mM), which suggested that PB-mediated DNA strand breaks and chromosome damage. To
      indicate the role of antioxidant in those effects, DNA migration was monitored by
      pre-treatment with hydroxytyrosol (HT) as an antioxidant in SCGE assay. It was
      found that DNA migration with pre-treatment of HT was dramatically decreased. To
      elucidate the genotoxicity mechanisms, the study monitored the levels of reactive
      oxygen species (ROS), glutathione (GSH) and 8-hydroxydeoxyguanosine (8-OHdG). PB
      was shown to induce ROS production (12.5 mM), GSH depletion (1.56-12.5 mM) and 8
      OHdG formation (6.25-12.5 mM) in HepG2 cells. Moreover, lysosomal membrane
      stability and mitochondrial membrane potential were further studied for the
      mechanisms of PB-induced genotoxicity. A significant increase was found in the
      range of 6.25-12.5 mM in lysosomal membrane stability assay. However, under these
      PB concentrations, we were not able to detect the changes of mitochondrial
      membrane potential. These results suggest that PB exerts oxidative stress and
      genotoxic effects in HepG2 cells, possibly through the mechanisms of lysosomal
      damage, an earlier event preceding the oxidative DNA damage.

PMID- 21182834
TI  - Akt2 and nucleophosmin/B23 function as an oncogenic unit in human lung cancer
      cells.
AB  - The signaling network of protein kinase B(PKB)/Akt has been implicated in
      survival of lung cancer cells. However, understanding the relative contribution
      of the different isoform of Akt network is nontrival. Here, we report that Akt2
      is highly expressed in human lung adenocarcinoma cell line A549 cells.
      Suppression of Akt2 expression in A549 cells results in notable inhibition of
      cell poliferation, soft agar growth, and invasion, accompanying by a decrease of
      nucleophosmin/B23 protein. Overexpression of Akt1 restores cancerous growth of
      A549 cells in B23-knockdown (KD) cells while Akt2 overexpression did not restore
      proliferating potential in cells with downregulated B23, thus suggesting Akt2
      requires B23 to drive proliferation of lung cancer cell. Loss of functional Akt2
      and B23 has similar defects on cell proliferation, apoptotic resistance and cell
      cycle regulation, while loss of Akt1 has less defects on cell proliferation,
      survival and cell cycle progression in A549 cells. Moreover, overexpression of
      B23 rescues the proliferative block induced as a consequence of loss of Akt2.
      Thus our data suggest that Akt2/B23 functions as an oncogenic unit to drive
      tumorigenesis of A549 lung cancer cells.

PMID- 21182835
TI  - Diverse functions of reactive cysteines facilitate unique biosynthetic processes
      of aggregate-prone interleukin-31.
AB  - Interleukin-31 (IL-31) is a member of the four helical-bundle gp130/IL-6 cytokine
      family. Despite its implicated roles in inflammatory diseases, the biosynthetic
      processes of IL-31 have been poorly investigated. A detailed understanding of IL
      31 biosynthesis and the nature of ligand-receptor interactions can provide
      insights into effective strategies for the design of therapeutic approaches. By
      using various heterologous protein expression systems, we demonstrated that
      murine IL-31 was secreted as inter-molecularly disulfide-bonded covalent
      aggregates. Covalently aggregated IL-31 appeared while trafficking in the
      secretory pathway, but was not actively retained in the ER. The aggregate
      formation was not caused by a dysfunctional ER quality control mechanism or an
      intrinsic limitation in protein folding capacity. Furthermore, secreted IL-31
      aggregates were part of a large complex composed of various pleiotropic secretory
      factors and immune-stimulators. The extent and the heterogeneous nature of
      aggregates may imply that IL-31 was erroneously folded, but it was capable of
      signaling through cognate receptors. Mutagenesis revealed the promiscuity of all
      five cysteines in inter-molecular disulfide formation with components of the
      hetero-aggregates, but no cysteine was required for IL-31 secretion itself. Our
      present study not only illustrated various functions that cysteines perform
      during IL-31 biosynthesis and secretion, but also highlighted their potential
      roles in cytokine effector functions.

PMID- 21182836
TI  - Slug contributes to the regulation of CXCL12 expression in human osteoblasts.
AB  - CXCL12/CXCR4 chemokine/receptor axis signaling has recently been found to play an
      important role in the remodeling of bone tissue, but little is known about the
      molecular mechanisms that are involved. The present study shows that CXCL12 is
      present at high levels both in human mesenchymal stem cells (hMSCs) and primary
      osteoblasts (hOBs). When osteogenesis was induced, CXCL12 expression was strictly
      confined to mineralized nodules. To investigate what mechanisms contribute to the
      maintenance of a correct expression of CXCL12 in bone cellular context, we
      analyzed the relationship between CXCL12 and Slug, a transcription factor
      recently associated with osteoblast maturation. By gene silencing and chromatin
      immunoprecipitation assay, we showed that both proteins are required for the
      mineralization process and CXCL12 is transcriptionally and functionally regulated
      by Slug, which is recruited at specific sites to its gene promoter in vivo. These
      findings showed for the first time a positive correlation between CXCL12
      signaling and Slug activity, thus corroborating the role of these two proteins in
      bone cellular context and suggesting a new potential target for bone tissue
      repair and regeneration.

PMID- 21182837
TI  - Tumor necrosis factor alpha promotes the expression of immunosuppressive proteins
      and enhances the cell growth in a human bone marrow-derived stem cell culture.
AB  - Mesenchymal stem cells (MSCs) are widely used in experimental treatments for
      various conditions that involve normal tissue regeneration via inflammatory
      repair. It is known that MSCs can secrete multiple soluble factors and suppress
      inflammation. Even though the effect of MSCs on inflammation has been extensively
      studied, the effect of inflammation on MSCs is poorly understood. One of the
      major cytokines released at the site of inflammation is tumor necrosis factor
      alpha (TNF-alpha) which is known to induce MSC invasion and proliferation.
      Therefore, we wanted to test the effects of TNF-alpha exposure on MSCs derived
      from human bone marrow. We found, as expected, that cell proliferation was
      significantly enhanced during TNF-alpha exposure. However, according to the cell
      surface marker analysis, the intensity of several antigens in the minimum
      criteria panel for MSCs proposed by International Society of Cellular Therapy
      (ISCT) was decreased dramatically, and in certain cases, the criteria for MSCs
      were not fulfilled. In addition, TNF-alpha exposure resulted in a significant but
      transient increase in human leukocyte antigen and CD54 expression. Additional
      proteomic analysis by two-dimensional difference gel electrophoresis and mass
      spectrometry revealed three proteins whose expression levels decreased and 8
      proteins whose expression levels increased significantly during TNF-alpha
      exposure. The majority of these proteins could be linked to immunosuppressive and
      signalling pathways. These results strongly support reactive and
      immunosuppressive activation of MSCs during TNF-alpha exposure, which might
      influence MSC differentiation stage and capacity.

PMID- 21182838
TI  - Matrin 3 as a key regulator of endothelial cell survival.
AB  - Matrin 3 is an integral component of nuclear matrix architecture that has been
      implicated in interacting with other nuclear proteins and thus modulating the
      activity of proximal promoters. In this study, we evaluated the contribution of
      this protein to proliferation of endothelial cells. To selectively modulate
      matrin 3 expression, we used siRNA oligonucleotides and transfection of cells
      with a pEGFP-N1-Mtr3. Our data indicate that downregulation of matrin 3 is
      responsible for reduced proliferation and leads to necrosis of endothelial cells.
      This conclusion is supported by observations that reducing matrin 3 expression
      results in (a) producing signs of necrosis detected by PI staining, LDH release,
      and scatter parameters in flow cytometry, (b) affecting cell cycle progression.
      It does not cause (c) membrane asymmetry of cells as indicated by lack of Annexin
      V binding as well as (d) activation of caspase 3 and cleavage of PARP. We
      conclude that matrin 3 plays a significant role in controlling cell growth and
      proliferation, probably via formation of complexes with nuclear proteins that
      modulate pro- and antiapoptotic signaling pathways. Thus, degradation of matrin 3
      may be a switching event that induces a shift from apoptotic to necrotic death of
      cells.

PMID- 21182839
TI  - Re-evaluating the general(ized) roles of AMPK in cellular metabolism.
AB  - AMPK is a protein kinase activated by various cellular stresses such as glucose
      deprivation, hypoxia or exercise. Despite having been studied for decades only a
      limited number of targets have been well described in tissues as varied as liver,
      muscle, and adipose tissue. Recent studies have shown that AMPK does not function
      in a similar manner, or through identical targets, in all cellular situations,
      posing challenges to some accepted paradigms describing AMPK function. A
      combination of genetic models and cell biological analysis of AMPK function in
      specific cell/developmental/environmental contexts will be required to accurately
      complement our understanding of the role(s) of AMPK in cancer, diabetes and other
      diseases.

PMID- 21182840
TI  - In vivo 6-thioguanine-resistant T cells from melanoma patients have public TCR
      and share TCR beta amino acid sequences with melanoma-reactive T cells.
AB  - In vivo hypoxanthine-guanine phosphoribosyltransferase (HPRT)-deficient T cells
      (MT) from melanoma patients are enriched for T cells with in vivo clonal
      amplifications that traffic between blood and tumor tissues. Melanoma is thus a
      model cancer to test the hypothesis that in vivo MT from cancer patients can be
      used as immunological probes for immunogenic tumor antigens. MT were obtained by
      6-thioguanine (TG) selection of lymphocytes from peripheral blood and tumor
      tissues, and wild-type T cells (WT) were obtained analogously without TG
      selection. cDNA sequences of the T cell receptor beta chains (TRB) were used as
      unambiguous biomarkers of in vivo clonality and as indicators of T cell
      specificity. Public TRB were identified in MT from the blood and tumor of
      different melanoma patients. Such public TRB were not found in normal control MT
      or WT. As an indicator of T cell specificity for melanoma, the >2600 MT and WT
      TRB, including the public TRB from melanoma patients, were compared to a
      literature-derived empirical database of >1270 TRB from melanoma-reactive T
      cells. Various degrees of similarity, ranging from 100% conservation to 3-amino
      acid motifs (3-mer), were found between both melanoma patient MT and WT TRBs and
      the empirical database. The frequency of 3-mer and 4-mer TRB matching to the
      empirical database was significantly higher in MT compared with WT in the tumor
      (p=0.0285 and p=0.006, respectively). In summary, in vivo MT from melanoma
      patients contain public TRB as well as T cells with specificity for characterized
      melanoma antigens. We conclude that in vivo MT merit study as novel probes for
      uncharacterized immunogenic antigens in melanoma and other malignancies.

PMID- 21182841
TI  - Detection of two different influenza A viruses using a nitrocellulose membrane
      and a magnetic biosensor.
AB  - Here we describe a new analytical method for the detection of two influenza A
      viruses by nitrocellulose membrane and magnetic sensors that employ a special
      frequency mixing technique. The combination of the nitrocellulose membrane and
      magnetic bead detection permits a rapid assay procedure and excludes two steps
      (the development of color and the stop reaction) required for usual
      immunochemical detection methods such as ELISA. Quantitative virus detection was
      performed using magnetic beads conjugated with secondary antibody. The results
      were compared with conventional assay methods and with a dot-blot assay with
      fluorescence compound (FITC). Under optimum conditions, our new assay procedure
      is capable of detecting picograms of virus per well. This new method combining
      the nitrocellulose membrane and magnetic bead detection reduces analytical time
      and allows stable and repeatable analyses of samples in point-of-care
      applications.

PMID- 21182842
TI  - A platform for complementation and characterization of familial haemophagocytic
      lymphohistiocytosis 3 mutations.
AB  - Mutations in UNC13D cause the severe immune disorder familial haemophagocytic
      lymphohistiocytosis type 3 (FHL3). The gene product munc13-4 is expressed in
      hematopoietic cells and is essential for degranulation. Little information is
      available on genotype-phenotype relationships of UNC13D mutations. Some mutants
      may have residual functionality which qualifies them as promising targets for
      attempts to enhance function pharmacologically. A problem for such analysis is
      the scarcity of patient material. We established assays in the RBL-2H3 cell line
      to assess functionality of lentivirally transduced munc13-4 mutants. The basic
      principle of which is to silence endogenous rat munc13-4 and replace it with
      siRNA resistant YFP-tagged human variants. Localization, degranulation, and
      membrane binding kinetics can now easily be analyzed quantitatively. Such a
      system might also be useful to screen small molecular weight compounds for their
      ability to rescue degranulation in cells with reduced functional munc13-4.

PMID- 21182844
TI  - Host range limitation caused by incomplete host regulation in an aphid
      parasitoid.
AB  - Defining host ranges in parasitoid insects is important both from a theoretical
      and an applied point of view. Based on the literature, some species seem able to
      use a wide range of hosts, while field studies indicate possible local host
      specialization. In koinobiont endoparasitoid species, such specialization could
      involve physiological processes. We tested the ability of two strains of the
      cosmopolitan and polyphagous parasitoid Diaeretiella rapae, to develop in three
      of its recorded aphid host species. Both strains produced high parasitism rates
      on the cabbage aphid Brevicoryne brassicae and the green peach aphid Myzus
      persicae but almost no progeny on the cherry-oat aphid Rhopalosiphum padi. This
      last species was less attacked by female parasitoids. Moreover, parasitoid eggs
      and larvae were smaller than in the two other host aphid species and their
      development was delayed. This abnormal development appeared to be due to an
      incomplete host regulation process, probably related to the low number and the
      size of teratocytes produced by D. rapae in R. padi individuals. Such a failure
      as far as gaining control of the host's metabolism is concerned could play an
      important role in shaping the host range of parasitoid insects, leading to local
      variation of the host spectrum in populations from various geographical areas.

PMID- 21182843
TI  - Plasmablast-derived polyclonal antibody response after influenza vaccination.
AB  - Conventional measurement of antibody responses to vaccines largely relies on
      serum antibodies, which are primarily produced by bone marrow plasma cells and
      may not represent the entire vaccine-induced B cell repertoire, including
      important functional components such as those targeted to mucosal sites. After
      immunization or infection, activated B cells differentiate into plasmablasts in
      local lymphoid organs, then traffic through circulation to the target sites where
      they further develop into plasma cells. On day 7 after influenza vaccination, a
      burst of plasmablasts, highly enriched for vaccine-specific antibody secreting
      cells, appears in the peripheral blood. This provides a unique window to the
      overall B cell response to the vaccine, without interference of pre-existing
      cross-reactive serum antibody. In this study we isolated B cells from volunteers
      on day 7 after immunization with the inactivated influenza vaccine and cultured
      them ex vivo to collect plasmablast-derived polyclonal antibodies (PPAb). The
      PPAb contained secreted IgG and IgA, which was approximately 0.2ng per antibody
      secreting cell. Influenza-specific IgG and IgA binding activity was detected in
      PPAb at dilutions up to 10(5) by ELISA. The ratio of the titers of influenza
      specific IgA to IgG by ELISA was 4-fold higher in PPAb than in day 28 post
      vaccination sera, suggesting that vaccine-induced IgA is enriched in PPAb
      compared to sera. Functional activity was also detected in PPAb as determined by
      microneutralization and hemagglutination inhibition assays. In addition to bulk B
      cell cultures, we also cultured plasmablast subsets sorted by cell surface
      markers to generate PPAb. These results suggest that PPAb better reflects the
      mucosal IgA response than serum samples. Since PPAb are exclusively produced by
      recently activated B cells, it allows assessing vaccine-induced antibody response
      without interference from pre-existing cross-reactive serum antibodies and
      permits an assessment of antibody avidity based on antigen specific binding and
      antibody quantity. Therefore this assay is particularly useful for studying
      vaccine/infection-induced antibodies against antigens that might have previously
      circulated, such as antibody responses to rotavirus, dengue or influenza viruses
      in which cross-reactive antibodies against different virus serotypes/subtypes
      play a critical role in immunity and/or pathogenesis.

PMID- 21182845
TI  - Reversal of inducible nitric oxide synthase uncoupling unmasks tolerance to
      ischemia/reperfusion injury in the diabetic rat heart.
AB  - The diabetic heart is known to be susceptible to ischemia/reperfusion (I/R)
      injury by increased oxidative stress. Although oxidative stress upregulates
      inducible nitric oxide (iNOS), the role of iNOS in I/R injury in the diabetic
      heart has been poorly understood. Because iNOS-derived nitric oxide (NO) plays a
      crucial role in cardioprotection against I/R injury, we hypothesized that
      inhibition of iNOS uncoupling would restore tolerance to I/R injury in the
      diabetic heart. The present study demonstrated that iNOS-derived superoxide
      generation was reduced, and that the NO bioavailability was increased, by
      treatment with the NOS-cofactor, tetrahydrobiopterin (BH4), before I/R in the
      hearts isolated from diabetic rats. This was associated with a reduction of
      infarct size and improvement of left ventricular (LV) function after I/R. The
      cardioprotective effect of BH4 was abrogated by treatment with a thiol reducing
      agent dithiothreitol (DTT), but not a NO-sensitive guanylyl cyclase inhibitor
      ODQ, suggesting that iNOS-derived NO-mediated cardioprotection occurs through
      protein S-nitrosylation but not cGMP-dependent signaling in the diabetic heart.
      Indeed, protein S-nitrosylation was increased by treatment with BH4 in the
      diabetic heart and was inhibited by DTT. These results suggest that the
      inhibition of iNOS uncoupling unmasks tolerance to I/R injury through enhanced
      protein S-nitrosylation in the diabetic rat heart.

PMID- 21182846
TI  - The importance of niche differentiation for coexistence on large scales.
AB  - It is widely accepted that niche differentiation plays a key role in coexistence
      on relatively small scales. With regard to a large community scale, the recently
      propounded neutral theory suggests that species abundances are more influenced by
      history and chance than they are by interspecies competition. This inference is
      mainly based on the probability that competitive exclusion is largely slowed by
      recruitment limitation, which may be common in species rich communities. In this
      respect, a theoretical study conducted by Hurtt and Pacala (1995) for a niche
      differentiated community has been frequently cited to support neutral
      coexistence. In this paper, we focused on the effect of symmetric recruitment
      limitation on delaying species competitive exclusion caused by both symmetric and
      asymmetric competition in a large homogeneous habitat. By removing niche
      differentiation in space, we found that recruitment limitation could delay
      competitive exclusion to some extent, but the effect was rather limited compared
      to that predicted by Hurtt and Pacala's model for a niche differentiated
      community. Our results imply that niche differentiation may be important for
      species coexistence even on large scales and this has already been confirmed in
      some species rich communities.

PMID- 21182847
TI  - A sampling theory for asymmetric communities.
AB  - We introduce the first analytical model of asymmetric community dynamics to yield
      Hubbell's neutral theory in the limit of functional equivalence among all
      species. Our focus centers on an asymmetric extension of Hubbell's local
      community dynamics, while an analogous extension of Hubbell's metacommunity
      dynamics is deferred to an appendix. We find that mass-effects may facilitate
      coexistence in asymmetric local communities and generate unimodal species
      abundance distributions indistinguishable from those of symmetric communities.
      Multiple modes, however, only arise from asymmetric processes and provide a
      strong indication of non-neutral dynamics. Although the exact stationary
      distributions of fully asymmetric communities must be calculated numerically, we
      derive approximate sampling distributions for the general case and for nearly
      neutral communities where symmetry is broken by a single species distinct from
      all others in ecological fitness and dispersal ability. In the latter case, our
      approximate distributions are fully normalized, and novel asymptotic expansions
      of the required hypergeometric functions are provided to make evaluations
      tractable for large communities. Employing these results in a bayesian analysis
      may provide a novel statistical test to assess the consistency of species
      abundance data with the neutral hypothesis.

PMID- 21182848
TI  - Geographic parthenogenesis in a consumer-resource model for sexual reproduction.
AB  - The phenomenon of geographic parthenogenesis is closely tied to the question of
      why sexual reproduction is the dominant mode of reproduction in animals and
      plants. Geographic parthenogenesis describes the fact that many species reproduce
      asexually at the boundaries of their range. We present a mathematical model that
      derives the dominance of sexuals at the center and the dominance of asexuals at
      the boundary of a species' range from exactly the same mechanism. Our model is
      based on a set of resources that regrow slowly and that can be consumed only by
      those individuals that have a suitable genotype. Genotype is implemented by a
      multilocus model with two alleles at each locus, and with free recombination
      during production of sexual offspring. The model is tailored to seasonal species
      with intermittent mixis and low survival of offspring, such as Daphnia and
      aphids. Several patches of resources are arranged in a row, with a gradient of
      those parameters that typically vary through the range of species. By letting
      sexually and asexually reproducing populations compete, we obtain the typical
      patterns of geographic parthenogenesis.

PMID- 21182849
TI  - Parametric modulation of error-related ERP components by the magnitude of visuo
      motor mismatch.
AB  - Errors generate typical brain responses, characterized by two successive event
      related potentials (ERP) following incorrect action: the error-related negativity
      (ERN) and the positivity error (Pe). However, it is unclear whether these error
      related responses are sensitive to the magnitude of the error, or instead show
      all-or-none effects. We studied error-monitoring with ERPs while healthy adult
      participants performed ballistic pointing movements towards a visual target with
      or without optical prisms, in alternating runs. This allowed us to record
      variable pointing errors, ranging from slight to large deviations relative to the
      visual target. Behavioural results demonstrated a classic effect of prisms on
      pointing (i.e. initial shifts away from targets, with rapidly improving
      performance), as well as robust prismatic after-effects (i.e. deviations in the
      opposite direction when removing the prisms after successful adaptation).
      Critically, the amplitude of both ERN and Pe were strongly influenced by the
      magnitude of errors. Error-related ERPs were observed for large deviations, but
      their amplitudes decreased monotonically when pointing accuracy increased,
      revealing a parametric modulation of monitoring systems as a function of the
      severity of errors. These results indicate that early error detection mechanisms
      do not represent failures in an all-or-none manner, but rather encode the degree
      of mismatch between the actual and expected motor outcome, providing a flexible
      cognitive control process that can discriminate between different degrees of
      mismatch between intentions and outcomes.

PMID- 21182850
TI  - Affective prosody: what do comprehension errors tell us about hemispheric
      lateralization of emotions, sex and aging effects, and the role of cognitive
      appraisal.
AB  - The Aprosodia Battery was developed to distinguish different patterns of
      affective-prosodic deficits in patients with left versus right brain damage by
      using affective utterances with incrementally reduced verbal-articulatory
      demands. It has also been used to assess affective-prosodic performance in
      various clinical groups, including patients with schizophrenia, PTSD, multiple
      sclerosis, alcohol abuse and Alzheimer disease and in healthy adults, as means to
      explore maturational-aging effects. To date, all studies using the Aprosodia
      Battery have yielded statistically robust results. This paper describes an
      extensive, quantitative error analysis using previous results from the Aprosodia
      Battery in patients with left and right brain damage, age-equivalent controls
      (old adults), and a group of young adults. This inductive analysis was performed
      to address three major issues in the literature: (1) sex and (2) maturational
      aging effects in comprehending affective prosody and (3) differential hemispheric
      lateralization of emotions. We found no overall sex effects for comprehension of
      affective prosody. There were, however, scattered sex effects related to a
      particular affect, suggesting that these differences were related to cognitive
      appraisal rather than primary perception. Results in the brain damaged groups did
      not support the Valence Hypothesis of emotional lateralization but did support
      the Right Hemisphere Hypothesis of emotional lateralization. When comparing young
      versus old adults, a robust maturational-aging effect was observed in overall
      error rates and in the distribution of errors across affects. This effect appears
      to be mediated, in part, by cognitive appraisal, causing an alteration in the
      salience of different affective-prosodic stimuli with increasing age. In
      addition, the maturational-aging effects lend support for the Emotion-Type
      hypothesis of emotional lateralization and the "classic aging effect" that is due
      primarily to decline of right hemisphere cognitive functions in senescence. The
      results of our inductive analysis may help direct future deductive research
      efforts, exploring the neuropsychology of emotional communication, by taking into
      account the potentially confounding influence of (1) methodological differences
      involving construction of test stimuli and assessment procedures, (2)
      developmental, maturational and aging effects related to cognitive appraisal and
      (3) whether a stimulus has a primary or social-emotional bias.

PMID- 21182851
TI  - Rapid amygdala gamma oscillations in response to fearful facial expressions.
AB  - Neuroimaging studies have reported greater activation of the human amygdala in
      response to emotional facial expressions, especially for fear. However, little is
      known about how fast this activation occurs. We investigated this issue by
      recording the intracranial field potentials of the amygdala in subjects
      undergoing pre-neurosurgical assessment (n=6). The subjects observed fearful,
      happy, and neutral facial expressions. Time-frequency statistical parametric
      mapping analyses revealed that the amygdala showed greater gamma-band activity in
      response to fearful compared with neutral facial expressions at 50-150 ms, with a
      peak at 135 ms. These results indicate that the human amygdala is able to rapidly
      process fearful facial expressions.

PMID- 21182852
TI  - Common neural mechanisms supporting spatial working memory, attention and motor
      intention.
AB  - The prefrontal cortex (PFC) and posterior parietal cortex (PPC) are critical
      neural substrates for working memory. Neural activity persists in these regions
      during the maintenance of a working memory representation. Persistent activity,
      therefore, may be the neural mechanism by which information is temporarily
      maintained. However, the nature of the representation or what is actually being
      represented by this persistent activity is not well understood. In this review,
      we summarize the recent functional magnetic resonance imaging (fMRI) studies
      conducted in our laboratory that test hypotheses about the nature of persistent
      activity during a variety of spatial cognition tasks. We find that the same areas
      in the PFC and PPC that show persistent activity during the maintenance of a
      working memory representation also show persistent activity during the
      maintenance of spatial attention and the maintenance of motor intention.
      Therefore, we conclude that persistent activity is not specific to working
      memory, but instead, carries information that can be used generally to support a
      variety of cognitions. Specifically, activity in topographically organized maps
      of prioritized space in PFC and PPC could be read out to guide attention
      allocation, spatial memory, and motor planning.

PMID- 21182853
TI  - Paternal genome effects on aging: evidence for a role of Rasgrf1 in longevity
      determination?
AB  - A recent study by Kawahara and Kono (2010) reports that mice artificially
      produced with two sets of female genomes have an increased average lifespan of
      28%. Moreover, these animals exhibit a smaller body size, a trait also observed
      in several other long-lived mouse models. One hypothesis is that alterations in
      the expression of paternally methylated imprinted genes are responsible for the
      life-extension of bi-maternal mice. Considering the similarities in postnatal
      growth retardation between mice with mutations in the Rasgrf1 imprinted gene and
      bi-maternal mice, Rasgrf1 is the most likely culprit for the low body weight and
      extended lifespan of bi-maternal mice. Rasgrf1 is a neuronal guanine-nucleotide
      exchange factor that induces Ras signaling in a calcium-dependent manner and has
      been implicated in learning and memory. Like other long-lived mouse strains,
      Rasgrf1 mutants are known to have low growth hormone and IGF-1 levels and the
      Rasgrf1 yeast homolog CDC25 had been previously associated with lifespan.
      Therefore, although the evidence is not conclusive, it does point towards the
      involvement of Rasgrf1 in the regulation of longevity, hypothetically through a
      mechanism similar to that observed in other long-lived mice of low GH/IGF-1
      signaling causing a low body weight and life-extension.

PMID- 21182854
TI  - Zolpidem-induced changes in activity, metabolism, and anxiety in rats.
AB  - Gamma aminobutyric acid (GABA)-A receptor modulators constitute the majority of
      clinically relevant sedative-hypnotics. Zolpidem (Ambien) is a nonbenzodiazepine
      GABA-A receptor modulator that binds with high affinity to GABA-A receptors
      expressing alpha-1 subunits. The present study examined the effects of a new
      approach to the oral administration of zolpidem on locomotor activity, body
      weight, food intake, relative food intake, feed efficiency, anxiety, and visceral
      adiposity in rats. Effects of withdrawal associated with cessation of the drug
      were also recorded. A daily chronically administered oral 10 mg/kg dose of
      zolpidem caused a decrease in locomotor activity, an increase in food intake and
      relative food intake, and a more positive feed efficiency during the drug
      administration period. Anxiety and visceral adiposity also increased in animals
      receiving the drug. During withdrawal of zolpidem, there was a decrease in body
      weight, food intake, relative food intake, and anxiety, as well as a negative
      feed efficiency. These results suggest that zolpidem can modulate locomotor
      activity, metabolism, and anxiety-related behavior. A highly positive feed
      efficiency and increased visceral adiposity associated with zolpidem intake were
      unique findings of this study.

PMID- 21182855
TI  - Seasonal and socio-demographic determinants of school commuting.
AB  - OBJECTIVE: To report prevalence of commuting to school in Norway with regard to
      season, gender, parental education level, ethnicity and distance to school.
      METHODS: Cross-sectional questionnaire data from the Fruits and Vegetables Make
      the Marks project collected in 2008, including 1339 ten to twelve-year-old
      children from 27 schools. The participants were categorized according to main
      mode of commuting to school in the three different school seasons (fall, winter
      and spring) and for the full school year if more than 50% of all trips were
      conducted by one specific mode. RESULTS: Most pupils (75%) were categorized as
      active commuters for the full school year. However, large seasonal variances were
      observed, especially for cycling. A total of 52%, 3% and 51% were categorized as
      cyclists in fall, winter and spring, respectively. Girls were more likely to be
      walkers (32% vs. 24%) and less likely to be cyclist (32% vs. 41%) than boys.
      Children of parents with higher education were more likely to be cyclist in fall
      (57% vs. 42%) and spring (56% vs. 40%), however, they were more likely to be
      walkers during winter time (71% vs. 56%). CONCLUSIONS: Most children reported
      that they were active commuters. Large seasonal variation was observed,
      especially regarding cycling.

PMID- 21182856
TI  - Grafting of softwood kraft pulps fibers with fatty acids under cold plasma
      conditions.
AB  - Cold plasma treatment is used to modify the cellulosic fibers for a variety of
      applications. The grafting of softwood unbleached (UBP) and bleached (BP) kraft
      pulp fibers has been performed under the action of cold plasma discharges, using
      different kinds of fatty acids. The grafted samples are characterized by FTIR
      spectroscopy, X-ray photoelectron spectroscopy (XPS), scanning electron
      microscopy (SEM), differential scanning calorimetry (DSC), termogravimetry (TG
      DTG) and X-ray diffraction (XRD). All these methods confirm the morphological and
      structural changes after plasma treatment which determines the modification in
      cellulosic fiber properties. The active centers created within the cellulose
      chains by plasma treatment were used to initiate grafting reactions with fatty
      acids. Such modification is useful to enhance the fibers properties such as
      softness and to change hydrophilic/hydrophobic balance.

PMID- 21182857
TI  - Fabrication of chitin-chitosan/nano TiO2-composite scaffolds for tissue
      engineering applications.
AB  - In this study, we prepared chitin-chitosan/nano TiO(2) composite scaffolds using
      lyophilization technique for bone tissue engineering. The prepared composite
      scaffold was characterized using SEM, XRD, FTIR and TGA. In addition, swelling,
      degradation and biomineralization capability of the composite scaffolds were
      evaluated. The developed composite scaffold showed controlled swelling and
      degradation when compared to the control scaffold. Cytocompatibility of the
      scaffold was assessed by MTT assay and cell attachment studies using osteoblast
      like cells (MG-63), fibroblast cells (L929) and human mesenchymal stem cells
      (hMSCs). Results indicated no sign of toxicity and cells were found attached to
      the pore walls within the scaffolds. These results suggested that the developed
      composite scaffold possess the prerequisites for tissue engineering scaffolds and
      it can be used for tissue engineering applications.

PMID- 21182858
TI  - Preparation, characterization and biocompatibility of electrospinning heparin
      modified silk fibroin nanofibers.
AB  - In this study, the electrospun silk fibroin nanofibrous scaffolds were modified
      with heparin by grafting after plasma treatment and blending electrospinning.
      Morphology, microstructure, chemical composition and grafting efficiency of the
      heparin-modified silk fibroin nanofibrous scaffolds were characterized to
      evaluate the effect of modification by means of scanning electron microscopy
      (SEM), Fourier transform infrared spectra (FTIR) and X-ray photoelectron
      spectrometer (XPS). The results showed that the heparin was successfully
      introduced to the silk fibroin nanofibrous scaffolds by both the two kinds of
      modification, and there was a hydrogen bonding between the silk fibroin and
      heparin. Moreover, the hydrophilicity, O-containing groups and negative charge
      density of the heparin-modified scaffolds were enhanced. In vitro coagulation
      time tests showed that the activated partial thromboplastin time (APTT),
      prothrombin time (PT) and thrombin time (TT) of the heparin-modified scaffolds
      were much higher than those of the pure silk fibroin scaffolds. L929 fibroblasts
      and EVCs spread and proliferated better on the heparin-modified scaffolds than on
      the pure silk fibroin scaffolds. Macrophages, neutrophils and lymphocytes were
      not observed in the heparin-modified scaffolds, which indicated that the modified
      scaffolds could induce minor inflammation in vivo. The results indicated that the
      electrospun heparin-modified silk fibroin nanofibrous scaffolds could be
      considered as ideal candidates for tissue engineering scaffolds.

PMID- 21182859
TI  - The immunoglobulin delta gene in jawed vertebrates: a comparative overview.
AB  - Immunoglobulin D (IgD) was recently suggested to be an ancient Ig class, as old
      as IgM, arising approximately 500 million years ago. Its encoding gene has now
      been identified in nearly all classes of jawed vertebrates (except birds).
      Variance in the number of CH encoding exons and alternative RNA splicing confers
      this Ig class a marked structural plasticity, which differs substantially from
      IgM. Expression of the delta gene can be achieved through co-transcription with
      the MU gene or by class switching. Although a recent study has suggested that IgD
      functions as an immunomodulator in immunity and inflammation in humans, its
      functions are still far from clear. Further studies at the protein levels in
      additional species may help answer this question.

PMID- 21182860
TI  - Invertebrate immune diversity.
AB  - The arms race between hosts and pathogens (and other non-self) drives the
      molecular diversification of immune response genes in the host. Over long periods
      of evolutionary time, many different defense strategies have been employed by a
      wide variety of invertebrates. We review here penaeidins and crustins in
      crustaceans, the allorecognition system encoded by fuhc, fester and Uncle fester
      in a colonial tunicate, Dscam and PGRPs in arthropods, FREPs in snails, VCBPs in
      protochordates, and the Sp185/333 system in the purple sea urchin. Comparisons
      among immune systems, including those reviewed here have not identified an immune
      specific regulatory "genetic toolkit", however, repeatedly identified sequences
      (or "building materials" on which the tools act) are present in a broad range of
      immune systems. These include a Toll/TLR system, a primitive complement system,
      an LPS binding protein, and a RAG core/Transib element. Repeatedly identified
      domains and motifs that function in immune proteins include NACHT, LRR, Ig,
      death, TIR, lectin domains, and a thioester motif. In addition, there are
      repeatedly identified mechanisms (or "construction methods") that generate
      sequence diversity in genes with immune function. These include genomic
      instability, duplications and/or deletions of sequences and the generation of
      clusters of similar genes or exons that appear as families, gene recombination,
      gene conversion, retrotransposition, alternative splicing, multiple alleles for
      single copy genes, and RNA editing. These commonly employed "materials and
      methods" for building and maintaining an effective immune system that might have
      been part of that ancestral system appear now as a fragmented and likely
      incomplete set, likely due to the rapid evolutionary change (or loss) of host
      genes that are under pressure to keep pace with pathogen diversity.

PMID- 21182862
TI  - Low-level lead exposure attenuates the expression of three major isoforms of
      neural cell adhesion molecule.
AB  - Toxic lead (Pb) exposure poses serious risks to human health, especially to
      children at developmental stages, even at low exposure levels. Neural cell
      adhesion molecule (NCAM) is considered to be a potential early target in the
      neurotoxicity of Pb due to its role in cell adhesion, neuronal migration,
      synaptic plasticity, and learning and memory. However, the effect of low-level Pb
      exposure on the specific expression of NCAM isoforms has not been reported. In
      the present study, we found that Pb could concentration-dependently (1-100 nM)
      inhibit the expression of three major NCAM isoforms (NCAM-180, -140, and -120) in
      primary cultured hippocampal neurons. Furthermore, it was verified that levels of
      all three major isoforms of NCAM were reduced by Pb exposure in human embryonic
      kidney (HEK)-293 cells transiently transfected with NCAM-120, -140, or -180
      isoform cDNA constructs. In addition, low-level Pb exposure delayed the neurite
      outgrowth and reduced the survival rate of cultured hippocampal neurons at
      different time-points. Together, our results demonstrate that developmental low
      level Pb exposure can attenuate the expression of all three major NCAM isoforms,
      which may contribute to the observed Pb-mediated neurotoxicity.

PMID- 21182861
TI  - Drug-sensitive reward in crayfish: an invertebrate model system for the study of
      SEEKING, reward, addiction, and withdrawal.
AB  - In mammals, rewarding properties of drugs depend on their capacity to activate
      appetitive motivational states. With the underlying mechanisms strongly conserved
      in evolution, invertebrates have recently emerged as a powerful new model in
      addiction research. In crayfish natural reward has proven surprisingly sensitive
      to human drugs of abuse, opening an unlikely avenue of research into the basic
      biological mechanisms of drug addiction. In a series of studies we first examined
      the presence of natural reward systems in crayfish, then characterized its
      sensitivity to a wide range of human drugs of abuse. A conditioned place
      preference (CPP) paradigm was used to demonstrate that crayfish seek out those
      environments that had previously been paired with the psychostimulants cocaine
      and amphetamine, and the opioid morphine. The administration of amphetamine
      exerted its effects at a number of sites, including the stimulation of circuits
      for active exploratory behaviors (i.e., SEEKING). A further study examined
      morphine-induced reward, extinction and reinstatement in crayfish. Repeated intra
      circulatory infusions of morphine served as a reward when paired with distinct
      visual or tactile cues. Morphine-induced CPP was extinguished after repeated
      saline injections. Following this extinction phase, morphine-experienced crayfish
      were once again challenged with the drug. The priming injections of morphine
      reinstated CPP at all tested doses, suggesting that morphine-induced CPP is
      unrelenting. In an exploration of drug-associated behavioral sensitization in
      crayfish we concurrently mapped measures of locomotion and rewarding properties
      of morphine. Single and repeated intra-circulatory infusions of morphine resulted
      in persistent locomotory sensitization, even 5 days following the infusion.
      Moreover, a single dose of morphine was sufficient to induce long-term behavioral
      sensitization. CPP for morphine and context-dependent cues could not be disrupted
      over a drug free period of 5 days. This work demonstrates that crayfish offer a
      comparative and complementary approach in addiction research. Serving as an
      invertebrate animal model for the exposure to mammalian drugs of abuse, modularly
      organized and experimentally accessible nervous systems render crayfish uniquely
      suited for studying (1) the basic biological mechanisms of drug effects, (2) to
      explore how the appetitive/seeking disposition is implemented in a simple neural
      system, and (3) how such a disposition is related to the rewarding action of
      drugs of abuse. This work aimed to contribute an evolutionary, comparative
      context to our understanding of a key component in learning, and of natural
      reward as an important life-sustaining process.

PMID- 21182863
TI  - Manganese is toxic to spiral ganglion neurons and hair cells in vitro.
AB  - Occupational exposure to high atmospheric levels of Mn produces a severe and
      debilitating disorder known as manganism characterized by extrapyramidal
      disturbances similar to that seen in Parkinson's disease. Epidemiological and
      case studies suggest that persistent exposures to Mn may have deleterious effects
      on other organs including the auditory system and hearing. Mn accumulates in the
      inner ear following acute exposure raising the possibility that it can damage the
      sensory hair cells that convert sound into neural activity or spiral ganglion
      neurons (SGN) that transmit acoustic information from the hair cells to the brain
      via the auditory nerve. In this paper we demonstrate for first time that Mn
      causes significant damage to the sensory hair cells, peripheral auditory nerve
      fibers (ANF) and SGN in cochlear organotypic cultures isolated from postnatal day
      three rats. The peripheral ANF that make synaptic contact with the sensory hair
      cells were particularly vulnerable to Mn toxicity; damage occurred at
      concentrations as low 0.01 mM and increased with dose and duration of Mn
      exposure. Sensory hair cells, in contrast, were slightly more resistant to Mn
      toxicity than the ANF. Mn induced an atypical pattern of sensory cell damage; Mn
      was more toxic to inner hair cells (IHC) than outer hair cells (OHC) and in
      addition, IHC loss was relatively uniform along the length of the cochlea. Mn
      also caused significant loss and shrinkage of SGN soma. These findings are the
      first to demonstrate that Mn can produce severe lesions to both neurons and hair
      cells in the postnatal inner ear.

PMID- 21182864
TI  - Iron deficiency increases blood manganese level in the Korean general population
      according to KNHANES 2008.
AB  - INTRODUCTION: We present data from Korean National Health and Nutritional
      Examination Survey (KNHANES) 2008 on the distribution of blood manganese (Mn)
      levels and their associations with iron deficiency in a representative sample of
      the adult Korean population. METHODS: This study was based on data obtained in
      KNHANES 2008, which was conducted for three years (2007-2009) using a rolling
      sampling design that involves a complex, stratified, multistage, probability
      cluster survey of a representative sample of the noninstitutionalized civilian
      population in South Korea. RESULTS: Geometric means (GMs) of blood Mn in the low
      serum ferritin group in women, men, and all participants were significantly
      higher than in the normal group. GMs of blood Mn in the low-normal serum ferritin
      groups in women and all participants were significantly higher than in the normal
      group. In addition, multiple regression analysis after controlling for covariates
      including gender, age, regional area, education level, and smoking and drinking
      status showed that blood Mn was significantly higher in the low ferritin group in
      women, men, and all participants compared with the normal group, whereas blood Mn
      was significantly higher in the low-normal ferritin group only in women and all
      participants. DISCUSSION: The present study shows that iron deficiency increases
      blood Mn level in the general population. To the best of our knowledge, the
      present study is the first to show an association between blood Mn level and
      ferritin level in a representative sample of the adult population such as that
      evaluated in KNHANES.

PMID- 21182865
TI  - Endocrine disruptors and childhood social impairment.
AB  - Prenatal exposure to endocrine disruptors has the potential to impact early brain
      development. Neurodevelopmental toxicity in utero may manifest as psychosocial
      deficits later in childhood. This study investigates prenatal exposure to two
      ubiquitous endocrine disruptors, the phthalate esters and bisphenol A (BPA), and
      social behavior in a sample of adolescent inner-city children. Third trimester
      urines of women enrolled in the Mount Sinai Children's Environmental Health Study
      between 1998 and 2002 (n=404) were analyzed for phthalate metabolites and BPA.
      Mother-child pairs were asked to return for a follow-up assessment when the child
      was between the ages of 7 and 9 years. At this visit, mothers completed the
      Social Responsiveness Scale (SRS) (n=137), a quantitative scale for measuring the
      severity of social impairment related to Autistic Spectrum Disorders (ASD) in the
      general population. In adjusted general linear models increasing log-transformed
      low molecular weight (LMW) phthalate metabolite concentrations were associated
      with greater social deficits (beta=1.53, 95% CI 0.25-2.8). Among the subscales,
      LMWP were also associated with poorer Social Cognition (beta=1.40, 95% CI 0.1
      2.7); Social Communication (beta=1.86, 95% CI 0.5-3.2); and Social Awareness
      (beta=1.25, 95% CI 0.1-2.4), but not for Autistic Mannerisms or Social
      Motivation. No significant association with BPA was found (beta=1.18, 95% CI 
      0.75, 3.11). Prenatal phthalate exposure was associated with childhood social
      impairment in a multiethnic urban population. Even mild degrees of impaired
      social functioning in otherwise healthy individuals can have very important
      adverse effects over a child's lifetime. These results extend our previous
      finding of atypical neonatal and early childhood behaviors in relation to
      prenatal phthalate exposure.

PMID- 21182868
TI  - Kalman filter mixture model for spike sorting of non-stationary data.
AB  - Nonstationarity in extracellular recordings can present a major problem during in
      vivo experiments. In this paper we present automatic methods for tracking time
      varying spike shapes. Our algorithm is based on a computationally efficient
      Kalman filter model; the recursive nature of this model allows for on-line
      implementation of the method. The model parameters can be estimated using a
      standard expectation-maximization approach. In addition, refractory effects may
      be incorporated via closely related hidden Markov model techniques. We present an
      analysis of the algorithm's performance on both simulated and real data.

PMID- 21182869
TI  - A simple method for fabricating microwire tetrode with sufficient rigidity and
      integrity without a heat-fusing process.
AB  - Heat-fusing is a common process for fabricating microwire tetrodes. However, it
      is time-consuming, and the high-temperature treatment can easily cause the
      insulation of the microwire to overheat leading to short circuits. We herein
      provide a simple, fast method to fabricate microwire tetrodes without the heat
      fusion process. By increasing the twisting density, we were able to fabricate
      tetrodes with good rigidity and integrity. This kind of tetrode showed good
      recording quality, penetrated the brain surface easily, and remained intact after
      chronic implantation. This method requires only general laboratory tools and is
      relatively simple even for inexperienced workers.

PMID- 21182866
TI  - Correlating neurobehavioral performance with biomarkers of organophosphorous
      pesticide exposure.
AB  - There is compelling evidence that adverse neurobehavioral effects are associated
      with occupational organophosphorous pesticide (OP) exposure in humans. Behavioral
      studies of pesticide applicators, greenhouse workers, agricultural workers and
      farm residents exposed repeatedly over months or years to low levels of OPs
      reveal a relatively consistent pattern of neurobehavioral deficits. However, only
      two studies have demonstrated a link between neurobehavioral performance and
      current biomarkers of OP exposure including blood cholinesterase (ChE) activity
      and urinary levels of OP metabolites. A variety of reasons may explain why so few
      studies have reported such correlations, including differing individual and group
      exposure histories, differing methodologies for assessing behavior and exposure,
      and lack of a reliable index of exposure. Alternatively, these data may suggest
      that current biomarkers (ChE, urine metabolites) are neither predictive nor
      diagnostic of the neurobehavioral effects of chronic OP pesticide exposures. This
      review focuses on the evidence that neurobehavioral performance deficits are
      associated with occupational OP pesticide exposure and concludes that research
      needs to return to the basics and rigorously test the relationships between
      neurobehavioral performance and both current (ChE and urine metabolites) and
      novel (e.g., inflammation and oxidative stress) biomarkers using human and animal
      models. The results of such studies are critically important because OP
      pesticides are widely and extensively used throughout the world, including
      situations where exposure controls and personal protective equipment are not
      routinely used.

PMID- 21182870
TI  - Automatic system for analysis of locomotor activity in rodents--a reproducibility
      study.
AB  - Automatic analysis of locomotion in studies of behavior and development is of
      great importance because it eliminates the subjective influence of evaluators on
      the study. This study aimed to develop and test the reproducibility of a system
      for automated analysis of locomotor activity in rats. For this study, 15 male
      Wistar were evaluated at P8, P14, P17, P21, P30 and P60. A monitoring system was
      developed that consisted of an open field of 1m in diameter with a black surface,
      an infrared digital camera and a video capture card. The animals were filmed for
      2 min as they moved freely in the field. The images were sent to a computer
      connected to the camera. Afterwards, the videos were analyzed using software
      developed using MATLAB(r) (mathematical software). The software was able to
      recognize the pixels constituting the image and extract the following parameters:
      distance traveled, average speed, average potency, time immobile, number of
      stops, time spent in different areas of the field and time immobile/number of
      stops. All data were exported for further analysis. The system was able to
      effectively extract the desired parameters. Thus, it was possible to observe
      developmental changes in the patterns of movement of the animals. We also discuss
      similarities and differences between this system and previously described
      systems.

PMID- 21182867
TI  - Is decabromodiphenyl ether (BDE-209) a developmental neurotoxicant?
AB  - Polybrominated diphenyl ether (PBDE) flame retardants have become ubiquitous
      environmental pollutants. The relatively higher body burden in toddlers and
      children has raised concern for their potential developmental neurotoxicity,
      which has been suggested by animal studies, in vitro experiments, and recent
      human epidemiological evidence. While lower brominated PBDEs have been banned in
      several countries, the fully brominated decaBDE (BDE-209) is still utilized,
      though manufacturers will discontinue production in the U.S.A. in 2013. The
      recent decision by the U.S. Environmental Protection Agency to base the reference
      dose (RfD) for BDE-209 on a developmental neurotoxicity study has generated some
      controversy. Because of its bulky configuration, BDE-209 is poorly absorbed and
      does not easily penetrate the cell wall. Its acute and chronic toxicities are
      relatively low, with the liver and the thyroid as the primary targets, though
      there is some evidence of carcinogenicity. A few animal studies have indicated
      that BDE-209 may cause developmental neurotoxicity, affecting motor and cognitive
      domains, as seen for other PBDEs. Limited in vivo and in vitro studies have also
      evidenced effects of BDE-209 on thyroid hormone homeostasis and direct effects on
      nervous cells, again similar to what found with other lower brominated PBDEs. In
      contrast, a recent developmental neurotoxicity study, carried out according to
      international guidelines, has provided no evidence of adverse effects on
      neurodevelopment, and this should be considered in a future re-evaluation of BDE
      209. While estimated exposure to BDE-209 in children is believed to be several
      orders of magnitude below the most conservative RfD proposed by the USEPA,
      questions remain on the extent and relevance of BDE-209 metabolism to lower
      brominated PBDEs in the environment and in humans.

PMID- 21182871
TI  - Evaluation of a new, rapid test for detecting HCV infection, suitable for use
      with blood or oral fluid.
AB  - The availability of a highly accurate, rapid, point-of-care test for hepatitis C
      virus (HCV) may be useful in addressing the problem of under-diagnosis of HCV, by
      increasing opportunities for testing outside of traditional clinical settings. A
      new HCV rapid test device (OraQuick(r) HCV Rapid Antibody Test), approved
      recently in Europe for use with venous blood, fingerstick blood, serum, plasma,
      or oral fluid was evaluated in a multi-center study and performance compared to
      established laboratory-based tests for detection of HCV. The HCV rapid test was
      evaluated in prospective testing of subjects with signs and/or symptoms of
      hepatitis, or who were at risk for hepatitis C using all 5 specimen types.
      Performance was assessed relative to HCV serostatus established by laboratory
      methods (EIA, RIBA and PCR) approved in Europe for diagnosis of hepatitis C
      infection. Sensitivity to antibody in early infection was also compared to EIA in
      27 seroconversion panels. In addition, the reliability of the oral fluid sample
      for accurate detection of anti-HCV was assessed by studying the impact of various
      potentially interfering conditions of oral health, use of oral care products and
      consumption of food and drink. In this large study of at-risk and symptomatic
      persons, the overall specificities of the OraQuick(r) HCV Rapid Antibody Test
      were equivalent (99.6-99.9%) for all 5 specimen types and the 95% CIs
      substantially overlapped. Overall sensitivities were virtually identical for
      venous blood, fingerstick blood, serum and plasma (99.7-99.9%). Observed
      sensitivity was slightly lower for oral fluid at 98.1% though the upper CI
      (99.0%) was equal to the lower CI for venous blood and fingerstick blood. Most of
      the HCV positive subjects which gave nonreactive results in oral fluid had
      serological and virological results consistent with resolved infection.
      Sensitivity for anti-HCV in early seroconversion was virtually identical between
      the HCV rapid test and EIA. Detection of anti-HCV in oral fluid appeared
      generally robust to conditions of oral health, consumption of food and drink and
      use of oral care products. The OraQuick(r) HCV Rapid Antibody Test demonstrated
      clinical performance that was equivalent to current laboratory-based EIA. This
      new, HCV rapid test appears suitable as an aid in the diagnosis of HCV infection
      and may increase testing opportunities due to its simplicity and flexibility to
      use multiple specimen types, including fingerstick blood and oral fluid.

PMID- 21182872
TI  - An improved PCR method for detection of HIV-1 proviral DNA of a wide range of
      subtypes and recombinant forms circulating globally.
AB  - Proviral DNAs are being measured increasingly as a marker of the efficacy of
      highly active anti-retroviral therapy (HAART) and is accepted for the early
      diagnosis of perinatal HIV-1 infections. This requires a standardized test which
      enables the detection of a wide range of subtypes worldwide including O, N and
      circulating recombinant forms (CRFs). Based on a previous publication, a PCR -
      Test for HIV-1 provirus detection in peripheral blood mononuclear cells (PBMCs)
      was developed. Blood samples from 80 individuals infected with HIV-1 and 20
      persons negative for HIV-1&2 from Africa and Germany were tested for the presence
      of HIV-1 provirus DNA. The primer system used enables the detection of proviral
      DNA despite the high concentrations of human DNA. The limit of detection was
      determined to be 5 copies per 10(5) cells. All 20 samples from persons negative
      for HIV were negative for HIV-1 proviral DNA while provirus DNA was amplified
      from 76 of the 80 (95%) samples from persons infected with HIV. The amplified
      products were detected by gel-electrophoresis, flow cytometry and real-time PCR.
      All three detection systems provided the same results.

PMID- 21182873
TI  - Oral putrescine restores virulence of ornithine decarboxylase-deficient
      Leishmania donovani in mice.
AB  - Administration of putrescine as a 1% solution in the drinking water ameliorated
      the profound loss of virulence exhibited by ornithine decarboxylase (ODC)
      deficient Leishmania donovani in mice. Furthermore, supplying alpha
      difluoromethylornithine, an ODC inhibitor, at 2% in the drinking water reduced
      but did not eliminate infection with wild type L. donovani in the mouse model.
      Taken collectively, these findings: (1) demonstrate that oral putrescine can
      access the phagolysosome of macrophages in which the parasite resides in mice;
      (2) establish that the loss of virulence due to the Deltaodc lesion is a
      consequence of the inability of the mutant parasite to synthesize sufficient
      polyamines de novo; (3) imply that the L. donovani amastigote cannot access host
      polyamines in sufficient amounts for survival and growth; (4) and validate ODC as
      a drug target, although oral administration of DFMO is an unlikely therapeutic
      paradigm for visceral leishmaniasis.

PMID- 21182874
TI  - Development of a real time PCR Taqman assay based on the TPI gene for
      simultaneous identification of Clostridium chauvoei and Clostridium septicum.
AB  - In the present study, a Taqman allelic discrimination assay based on three SNPs
      of the TPI gene is described. It was used as a differential diagnostic tool to
      detect blackleg and malignant edema. Sudden deaths of grazing ruminants, such as
      cattle, sheep and goats, which show clinical signs related to hyperacute
      infective processes, encouraged the development of a rapid and precise diagnostic
      molecular method. Specific primers and probes for Clostridium septicum and
      Clostridium chauvoei were designed on the basis of the TPI gene sequence. The
      multiplex PCR was tested on the DNA of a total of 57 strains, including 24
      Clostridium chauvoei, 20 Clostridium septicum, 1 Bacillus anthracis and 12 other
      Clostridium spp. The DNA samples from Clostridium chauvoei and Clostridium
      septicum strains were amplified. Amplification of other DNA samples was not
      observed, with the exception of Clostridium tertium, which showed a weak positive
      signal. To avoid misdiagnosis, a confirmatory assay based on a Sybr green real
      time PCR was proposed. The authors confirmed the efficacy and the specificity of
      the test used in this study, which proved to be a useful tool for the diagnosis
      of clostridiosis that are often diagnosed using only traditional tools.

PMID- 21182875
TI  - Perilla frutescens seed agar, a new medium for identification of the Cryptococcus
      species complex: evaluation for all major molecular types.
AB  - Here we present a new and simple medium made by Perilla frutescens seed as a tool
      for identification of the Cryptococcus species complex, namely Cryptococcus
      neoformans and Cryptococcus gattii. Its usefulness was evaluated for all major
      molecular types within the Cryptococcus species complex. As a result, this medium
      is better for identification of the species complex compared with Guizotia
      abyssinica or Helianthus annuus seed medium.

PMID- 21182876
TI  - PCR-based community structure studies of bacteria associated with eukaryotic
      organisms: a simple PCR strategy to avoid co-amplification of eukaryotic DNA.
AB  - PCR primers targeting conserved regions of the SSU rRNA gene are commonly used in
      bacterial community studies. For microbes associated with eukaryotes, co
      amplification of eukaryotic DNA may preclude the analysis. We present a simple
      and efficient PCR strategy to obtain pure bacterial rDNA amplicons from samples
      predominated by eukaryotic DNA.

PMID- 21182877
TI  - Development of a URA5 integrative cassette for gene disruption in the Candida
      guilliermondii ATCC 6260 strain.
AB  - We designed an efficient transformation system for Candida guilliermondii based
      on a ura5 ATCC 6260 derived recipient strain and a URA5 recyclable selection
      marker. This "URA5 blaster" disruption system represents a powerful tool to study
      the function of a large pallet of genes in this yeast of clinical and
      biotechnological interest.

PMID- 21182878
TI  - A new methodology for rapid detection of Lactobacillus delbrueckii subsp.
      bulgaricus based on multiplex PCR.
AB  - In this study we present a novel multiplex PCR assay for rapid and efficient
      detection of Lactobacillus delbrueckii subsp. bulgaricus. The accuracy of our
      method was confirmed by the successful identification of L. delbrueckii subsp.
      bulgaricus in commercial yoghurts and food supplements and it may be readily
      applied to the food industry.

PMID- 21182879
TI  - Expansion of the known Klebsiella pneumoniae species gene pool by
      characterization of novel alien DNA islands integrated into tmRNA gene sites.
AB  - Klebsiella pneumoniae is an important bacterial pathogen of man that is commonly
      associated with opportunistic and hospital-associated infections. Increasing
      levels of multiple-antibiotic resistance associated with this species pose a
      major emerging clinical problem. This organism also occurs naturally in other
      diverse environments, including the soil. Consistent with its varied lifestyle
      and membership of the Enterobacteriaceae family, K. pneumoniae genomes exhibit
      highly plastic architecture comprising a core genome backbone interspersed with
      numerous and varied alien genomic islands. In this study the size of the
      presently known K. pneumoniae pan-genome gene pool was estimated through analysis
      of complete sequences of three chromosomes and 31 plasmids belonging to K.
      pneumoniae strains. In addition, using a PCR-based strategy the genomic content
      of eight tRNA/tmRNA gene sites that serve as DNA insertion hotspots were
      investigated in 28 diverse environmental and clinical strains of K. pneumoniae.
      Sequencing and characterization of five newly identified horizontally-acquired
      tmRNA-associated islands further expanded the archived K. pneumoniae gene pool to
      a total of 7648 unique gene members. Large-scale investigation of the content of
      tRNA/tmRNA hotspots will be useful to identify and/or survey accessory sequences
      dispersed amongst hundreds to thousands of members of many key bacterial species.

PMID- 21182880
TI  - Proposal of protocols using D-glutamine to optimize the 2,3-bis(2-methoxy-4-nitro
      5-sulfophenly)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide (XTT) assay for
      indirect estimation of microbial loads in biofilms of medical importance.
AB  - Due to technical problems, biofilm biomasses are difficult to be precisely
      determined. One reliable strategy is based on the colorimetry of formazan
      compounds derived from tetrazolium salt reduction. XTT presents some desirable
      properties that make the biofilm measurements easier. However, cells entrapped
      within the extracellular matrixes normally do not metabolize the tetrazolium
      equally, leading to underestimation of cell contents. This study evaluated the
      effectiveness of D-glutamine, a plerotic substrate of tricarboxilic acid cycle
      (TAC), as inducer of XTT reduction. The metabolic activities of aerobic and
      anaerobic 48 h-old monospecific biofilms of Pseudomonas aeruginosa
      ATCC(r)27853TM, Klebsiella pneumoniae ATCC(r)13883TM, Staphylococcus epidermidis
      ATCC(r)12228TM, Streptococcus mutans ATCC(r)25175TM, and Candida albicans SC5314
      were evaluated. Results showed that D-glutamine 50 mM (for P. aeruginosa, K.
      pneumoniae, and S. epidermidis) and 25 mM (for S. mutans and C. albicans) may
      enhance the detection of soluble formazan in a significant manner, what becomes
      the XTT reduction assay more robust.

PMID- 21182881
TI  - Enhanced pulmonary absorption of a macromolecule through coupling to a sequence
      specific phage display-derived peptide.
AB  - With the aim of identifying a peptide sequence that promotes pulmonary epithelial
      transport of macromolecule cargo we used a stringent peptide-phage display
      library screening protocol against rat lung alveolar epithelial primary cell
      cultures. We identified a peptide-phage clone (LTP-1) displaying the disulphide
      constrained 7-mer peptide sequence, C-TSGTHPR-C, that showed significant
      pulmonary epithelial translocation across highly restrictive polarised cell
      monolayers. Cell biological data supported a differential alveolar epithelial
      cell interaction of the LTP-1 peptide-phage clone and the corresponding free
      synthetic LTP-1 peptide. Delivering select phage-clones to the intact pulmonary
      barrier of an isolated perfused rat lung (IPRL) resulted in 8.7% of lung
      deposited LTP-1 peptide-phage clone transported from the IPRL airways to the
      vasculature compared (p<0.05) to the cumulative transport of less than 0.004% for
      control phage-clone groups. To characterise phage-independent activity of LTP-1
      peptide, the LTP-1 peptide was conjugated to a 53kDa anionic PAMAM dendrimer.
      Compared to respective peptide-dendrimer control conjugates, the LTP-1-PAMAM
      conjugate displayed a two-fold (bioavailability up to 31%) greater extent of
      absorption in the IPRL. The LTP-1 peptide-mediated enhancement of transport, when
      LTP-1 was either attached to the phage clone or conjugated to dendrimer, was
      sequence-dependent and could be competitively inhibited by co-instillation of
      excess synthetic free LTP-1 peptide. The specific nature of the target receptor
      or mechanism involved in LTP-1 lung transport remains unclear although the
      enhanced transport is enabled through a mechanism that is non-disruptive with
      respect to the pulmonary transport of hydrophilic permeability probes. This study
      shows proof-of principle that array technologies can be effectively exploited to
      identify peptides mediating enhanced transmucosal delivery of macromolecule
      therapeutics across an intact organ.

PMID- 21182883
TI  - Measuring thinspiration and fear of fat indirectly. A matter of approach and
      avoidance.
AB  - The concepts thinspiration and fear of fat are crucial regarding the development
      and maintenance of body image disturbances and eating pathology. This study aimed
      to advance our current understanding of these two motivational concepts. Unlike
      previous studies that have primarily relied on self report measures to
      investigate thinspiration and fear of fat, we applied an indirect measure, namely
      a Stimulus Response Compatibility (SRC) task. During our SRC task, undergraduate
      female students were instructed to symbolically approach and avoid pictures of
      thin and chubby models. Hence, the participants' reaction times during the SRC
      task provided an index of the automatic affective and motivational valence of the
      models. Results showed that participants were faster to approach than to avoid
      thin models, however, there was no difference in approach-avoidance responses
      regarding chubby models. Analyses revealed that the approach-avoidance responses
      were related to important eating-related, cognitive schemata, e.g., the
      participants' level of drive for thinness, thin-ideal internalization, body
      dissatisfaction and their weight control behaviors. These findings clearly
      support the application of an indirect measure such as the SRC task in order to
      examine the concepts thinspiration and fear of fat, and highlight the need for
      further research that validates and extends current results.

PMID- 21182882
TI  - Links between mothers' and children's disinhibited eating and children's
      adiposity.
AB  - Few studies have examined relationships between parents' and children's specific
      disinhibited eating behaviors. We investigated links among mothers' and
      children's binge/loss of control eating, eating in the absence of hunger, and
      children's adiposity in 305 non-treatment-seeking youth, aged 8-17 years (13.62+/
      2.65 years; 49.8% female) and their mothers. Youths' loss of control eating and
      eating in the absence of hunger were assessed by interview and self-report
      questionnaire. Children's adiposity was assessed with BMI-z and air displacement
      plethysmography. Maternal binge eating, eating in the absence of hunger and
      highest, non-pregnant BMI were self-reported. In structural equation models
      controlling for mothers' BMI, mothers' binge eating related to children's loss of
      control eating, and mothers' eating in the absence of hunger related to
      children's eating in the absence of hunger. Mothers' binge eating and children's
      eating in the absence of hunger were unrelated, as were mothers' eating in the
      absence of hunger and children's loss of control. Further, mothers' binge eating
      was indirectly related to children's adiposity through children's loss of control
      eating. Likewise, mothers' eating in the absence of hunger indirectly related to
      children's adiposity through children's eating in the absence of hunger. Mothers
      and children share similar, specific disinhibited eating styles.

PMID- 21182884
TI  - Grasping a fruit. Hands do what flavour says.
AB  - Previous research on multisensory integration during goal-directed natural
      actions reported that visual, proprioceptive, auditory and orthonasal olfactory
      stimulation has the ability to influence motor control. In this study, we used
      kinematics to investigate the integration between vision and flavour perception
      during reach-to-grasp movements. Participants were requested to drink a sip of
      flavoured solution and then grasp an object presented in central vision. The
      results indicate that when the objects evoked by the flavour and by the visual
      target were of a similar size (i.e., large or small) and evoked the same kind of
      hand shaping in order to be grasped (i.e., congruent condition) facilitation
      effects emerged. Conversely, when the object evoked by the flavour and by the
      visual target was of a different size and evoked a different kind of hand shaping
      in order to be grasped (i.e., incongruent condition) interference effects
      emerged. Interference effects, however, were only evident for the combination
      involving a large visual target and a 'small' flavour. When comparing hand
      kinematics between the congruent and a 'no flavour' condition (i.e., water),
      facilitation effects emerged in favour of the former condition. Taken together,
      these results indicate the contribution of complex chemosensory stimuli for the
      planning and execution of visually guided reach to grasp movements. And,
      contribute to the current debate regarding the multisensory nature of the
      sensorimotor transformations underlying motor performance.

PMID- 21182886
TI  - Peroxynitrite-induced modification of H2A histone presents epitopes which are
      strongly bound by human anti-DNA autoantibodies: role of peroxynitrite-modified
      H2A in SLE induction and progression.
AB  - Peroxynitrite is a potent oxidant and nitrating agent and has in vivo existence.
      It is a powerful proinflammatory substance and may increase vascular permeability
      in inflamed tissues. Systemic lupus erythematosus (SLE) is an autoimmune
      inflammatory disease of unknown etiology. Since its discovery, numerous self- and
      non-self, nuclear, and cytoplasmic antigens have been suggested as stimuli for
      SLE initiation, but the exact trigger is yet to be identified. In this study, an
      attempt has been made to investigate the binding characteristics of SLE anti-DNA
      autoantibodies to native DNA and native and peroxynitrite-modified H2A histone to
      explore the possible role of modified protein antigen(s) in SLE initiation and
      progression. The nuclear protein (H2A histone) was modified by peroxynitrite
      synthesized in our laboratory. The peroxynitrite-modified H2A revealed generation
      of nitrotyrosine, dityrosine, and carbonyls when subjected to investigation by
      physicochemical methods. Binding characteristics and specificity of SLE anti-DNA
      antibodies were analyzed by direct binding and inhibition enzyme-linked
      immunosorbent assay. The data show preferential binding of SLE autoantibodies to
      peroxynitrite-modified H2A histone in comparison with native H2A histone or
      native DNA. A band shift assay further substantiated the enhanced recognition of
      peroxynitirite-modified H2A histone by anti-DNA autoantibodies. The results
      suggest that peroxynitrite modification of self-antigen(s) can generate
      neoepitopes capable of inducing SLE characteristic autoantibodies. The
      preferential binding of peroxynitrite-modified H2A histone by SLE anti-DNA
      antibodies points out the likely role of oxidatively modified and nitrated H2A
      histone in the initiation/progression of SLE. Moreover, oxidatively modified and
      nitrated nuclear protein antigen, rather than nucleic acid antigens, appear to be
      more suitable as a trigger for SLE.

PMID- 21182887
TI  - Appreciating symptoms and deficits in schizophrenia: right posterior insula and
      poor insight.
AB  - Poor insight is one of the most prominent clinical features of psychosis. Loss of
      insight in schizophrenia is characterised by abnormalities in awareness and
      attribution of the origin of pathological mental phenomena. Converging lines of
      investigations suggest that in healthy individuals, right posterior insula plays
      an important role in awareness and self-attribution of mental phenomena,
      contributing to the emergence of a sense of self (Craig, 2002; Farrer et al.,
      2003). In addition, neuroimaging studies investigating brain morphometry in
      schizophrenia have consistently reported deficits in the structure of insula
      (Glahn et al., 2008; Ellison-Wright and Bullmore, 2010). In the present study, we
      investigated the relationship between the morphometry of posterior insula and
      degree of insight in a sample of 57 patients in a stable phase of illness using
      high resolution Magnetic Resonance Imaging. We measured the cortical surface area
      and local white matter volume of posterior insula. A significant inverse
      relationship was found between right posterior insular structure and degree of
      insight in schizophrenia. No such relationship was noted for left posterior
      insula. Our results highlight the importance of a predominantly right-sided
      network that includes posterior insula as the neural basis of insight.
      Abnormalities in interoceptive awareness and self-appraisal of emotional states
      may contribute to the loss of insight seen in schizophrenia.

PMID- 21182888
TI  - Reversion of the human calreticulin gene promoter to the ancestral type as a
      result of a novel psychosis-associated mutation.
AB  - Development-dependent, tissue-specific expression of the calreticulin (CALR) gene
      in the gray matter coincides with the expression of psychoses phenotypes. We have
      recently reported instances of mutations within the core promoter sequence of the
      gene in schizoaffective disorder. In view of the mounting evidence on the genetic
      overlap in the psychiatric spectrum, we investigated this gene in a spectrum of
      patients afflicted with schizophrenia, schizoaffective disorder and major
      affective disorder. We found that a unique mutation at nucleotide -220 from the
      transcription start site, located at a conserved genomic block in the promoter
      region of the gene, co-occurs with the spectrum of psychoses (p<0.005). This
      mutation reverts the human promoter sequence to the ancestral type observed in
      chimpanzee, mouse, and several other species, implying that the genomic block
      harboring nucleotide -220 may be involved in the evolution of human-specific
      higher-order functions of the brain (e.g. language, conceptual thinking, and
      judgment), that are ubiquitously impaired in psychoses. We propose that CALR is
      not only a promising candidate in the spectrum of psychoses, but also, a gene
      that may be important in the human-unique brain processes.

PMID- 21182889
TI  - A novel model integrated concentration addition with independent action for the
      prediction of toxicity of multi-component mixture.
AB  - Concentration addition (CA) and independent action (IA) have been used to
      describe the mixture of components having similar and dissimilar mode of action
      (MOA), respectively. Environmentally relevant mixture does, however, not follow
      the strictly similar or dissimilar MOA. A novel model, which integrated CA with
      IA based on the multiple linear regression (ICIM), was proposed for predicting
      the toxicity of noninteractive mixture. The predictive power of the ICIM model
      was validated by data set 1 including 13 mixtures of nine components and data set
      2 including six mixtures of six components. For data set 1, ten uniform design
      with fixed concentration ratio ray (UDCR) mixtures was used as a training set to
      build an ICIM model, and the model was used to predict the toxicity of the test
      set consisting of three equivalent-effect concentration ratio (EECR) mixtures.
      For data set 2, the ICIM model based on four UDCR mixtures was used to predict
      the remaining two EECR mixtures. It is concluded that the ICIM model shows a
      strong predictive power for the mixture toxicities in the two data sets, and its
      prediction is better than CA and IA where the two models deviate from the
      concentration-response data of the mixtures. Thus, ICIM model is a powerful tool
      to evaluate and predict mixture toxicity, and maybe offer an important approach
      in risk assessment of mixture toxicity.

PMID- 21182890
TI  - Sleep effects on slow-brain-potential reflections of associative learning.
AB  - Previous research has indicated that information acquired before sleep gets
      consolidated during sleep. This process of consolidation might be reflected after
      sleep in changed extent and topography of cortical activation during retrieval of
      information. Here, we designed an experiment to measure those changes by means of
      slow event-related EEG potentials (SPs). Retrieval of newly learnt verbal or
      spatial associations was tested both immediately after learning and two days
      later. In the night directly following immediate recall, participants either
      slept or stayed awake. In line with previous studies, SPs measured during
      retrieval from memory had parietal or left-frontal foci depending on whether the
      retrieved associations were spatial or verbal. However, contrary to our
      expectations, sleep-related consolidation did not further accentuate these
      content-specific topographic profiles. Rather, sleep modified SPs independently
      of the spatial or verbal type of learned association: SPs were reduced more after
      sleep than after waking specifically for those stimulus configurations that had
      been presented in the same combination at retrieval before sleep. The association
      independent stimulus-specific effect might generally form a major component of
      sleep-related effects on memory.

PMID- 21182891
TI  - Autonomic nervous system reactivity to positive and negative mood induction: the
      role of acute psychological responses and frontal electrocortical activity.
AB  - The differential effects of positive versus negative emotions on autonomic
      nervous system activity are insufficiently understood. This study examined the
      role of acute mood responses and central nervous system activity on heart rate
      variability (HRV) using 5-min event recall tasks (happiness and anger recall) and
      a 5-min Stroop Color Word Test (SCWT) in 20 healthy individuals (mean age 25 +/-
      4 years, 55% female). HRV was measured in high frequency (HF) and low frequency
      (LF) domains, and frontal brain activity using electroencephalography (EEG) in
      the alpha frequency band in F3 and F4. Happiness Recall resulted in increased LF
      HRV (p = 0.005) but not HF-HRV (p=0.71). Anger Recall did not change HRV (p
      values > 0.10). The SCWT produced decreases in HF-HRV (p = 0.001) as well as LF
      HRV (p = 0.001). The magnitude of feeling "happy" during Happiness Recall was
      positively correlated with DeltaHF-HRV (p = 0.050), whereas an incongruent mood
      state ("frustrated") was associated with smaller DeltaHF-HRV (p = 0.070).
      Associations between frontal EEG activation and HRV responses were mostly non
      significant, except for increased right frontal activation during Happiness
      Recall which was associated with a decrease in LF/HF ratio (p = 0.009). It is
      concluded that positive and negative mood induction result in differential HRV
      responses, which is related to both task valence and the intensity of task
      induced emotions.

PMID- 21182892
TI  - The Kruppel-like factor 4 controls biosynthesis of thyrotropin-releasing hormone
      during hypothalamus development.
AB  - Embryonic neurogenesis is controlled by the activation of specific genetic
      programs. In the hypothalamus, neuronal thyrotropin-releasing hormone (TRH)
      populations control important physiological process, including energy homeostasis
      and autonomic function; however, the genetic program leading to the TRH
      expression is poorly understood. Here, we show that the Klf4 gene, encoding the
      transcription factor Kruppel-like factor 4 (Klf4), was expressed in the rat
      hypothalamus during development and regulated Trh expression. In rat fetal
      hypothalamic cells Klf4 regulated Trh promoter activity through CACCC and GC
      motifs present on the Trh gene promoter. Accordingly, hypothalamic Trh expression
      was down-regulated at embryonic day 15 in the Klf4(-/-) mice resulting in
      diminished bioactive peptide levels. Although at the neonatal stage the Trh
      transcript levels of the Klf4(-/-) mice were normal, the reduction in peptide
      levels persisted. Thus, our data indicate that Klf4 plays a key role in the
      maturation of TRH expression in hypothalamic neurons.

PMID- 21182893
TI  - Multiple expression of glucose transporters in the lateral wall of the cochlear
      duct studied by quantitative real-time PCR assay.
AB  - We have investigated the gene expression of the facilitated glucose transporter
      (GLUT), H+-coupled myo-inositol cotransporter (HMIT), and Na+ glucose
      cotransporter (SGLT) in the lateral wall of the cochlear duct by conventional RT
      PCR and quantitative real-time PCR. The isoforms GLUT1, -3, -4, -5, -8, -10, -12
      and HMIT were detected in both the stria vascularis and the spiral ligament,
      whereas no SGLT isoforms could be detected in these tissues. Quantitative real
      time PCR analysis revealed significant differences in the gene expression of
      GLUT1, -4, -5, -10, and HMIT isoforms between the stria vascularis and the spiral
      ligament. This result reflects the tissue-dependent distributions of GLUT
      isoforms. These findings strongly suggest that a number of GLUT isoforms
      participate in glucose transport in the stria vascularis and the spiral ligament.

PMID- 21182894
TI  - A rat model of bone inflammation-induced pain by intra-tibial complete Freund's
      adjuvant injection.
AB  - In prior studies, models of inflammatory pain were produced through injecting
      complete Freund's adjuvant (CFA) or capsaicin directly into either the deep
      somatic tissue or the animal's hind paw. In contrast, bone cancer-induced pain
      (BCIP) was simulated through injecting tumor cells into the cavity of the femur
      or the tibia. It has been reported that, due to differences in afferent
      innervation, the same stimulus to various tissue types might result in differing
      patterns of pain response. Hence, the aim of this study is to establish a rat
      model of bone inflammation-induced pain (BIIP) by injecting CFA into the tibial
      cavity, the same site involved in the BCIP model. The differences in body weight,
      bone histology, mechanical allodynia, thermal hyperalgesia, and the pain
      relieving effects of Celebrex on this model of BIIP were evaluated. The results
      showed that there was evidence of significant inflammation seen in the bone
      marrow two days after intra-tibial CFA injection, including nuclear condensation
      and fragmentation, massive neutrophilic granulocytes, and prominent fibrinous
      exudates. Fourteen days after injection, marked fibrosis of the bone was detected
      by histological staining. After unilateral CFA injection, behavioral studies
      showed mechanical allodynia to von Frey hair stimulation, but no thermal
      hyperalgesia was observed. Celebrex showed significant anti-allodynic effects on
      the BIIP model. The results demonstrated that CFA is an effective agent for
      inducing bone inflammation and subsequent pain-related behavior in rat models,
      and, thus, provides a practical and valuable contrast for BCIP research.

PMID- 21182895
TI  - Conflict control of children with different intellectual levels: an ERP study.
AB  - Conflict control is an important cognitive ability in human behavioral
      regulation. The Eriksen flanker task was employed to explore the neural
      correlation between conflict control and intelligence with the aid of event
      related potential (ERP) techniques. Two groups of early adolescents with
      different intellectual levels participated in the current study (an
      intellectually gifted group of 20 children vs. an intellectually average group of
      21 children, with mean scores of 43 vs. 35.7 in Cattell's Culture Fair Test,
      respectively). Behavioral results indicate that the gifted children had better
      conflict control performances, with increased accuracy and faster response speeds
      than the intellectually average children. Electrophysiological results further
      show that the gifted children had more efficient N2 activations during conflict
      monitoring processing, faster P3 responses over frontal regions, and stronger P3
      activations over central-parietal regions during attentional control processing.
      The difference waveform analysis showed that the gifted children had the weakest
      N2d activations when elicited by multiple conflicts. N2d amplitudes can be used
      to distinguish a stimulus conflict from a response conflict, and P3d amplitudes
      can be used to separate multiple conflicts from a single conflict. The results
      support the neural efficiency hypothesis of intelligence and shed light on the
      close relationship between conflict control ability and human intelligence.

PMID- 21182896
TI  - TPH2 polymorphisms and alcohol-related suicide.
AB  - Substantial evidence from family, twin, and adoption studies corroborates
      implication of genetic and environmental factors, as well as their interactions,
      on suicidal behavior and alcoholism risk. Serotonergic disfunction seems to be
      involved in the pathophysiology of substance abuse, and has also an important
      role in suicidal behavior. Recent studies of the tryptophan hydroxylase 2 showed
      mild or no association with suicide and alcohol-related suicide. We performed SNP
      and alcohol analysis on 388 suicide victims and 227 controls. The results showed
      association between suicide (Pchi2=0.043) and alcohol-related suicide
      (Pchi2=0.021) for SNP Rs1843809. A tendency for association was determined also
      for polymorphism Rs1386493 (Pchi2=0.055) and alcohol-related suicide. Data
      acquired from psychological autopsies in a subsample of suicide victims (n=79)
      determined more impulsive behavior (Pchi2=0.016) and verbal aggressive behavior
      (Pchi2=0.025) in the subgroup with alcohol misuse or dependency. In conclusion,
      our results suggest implication of polymorphisms in suicide and alcohol-related
      suicide, but further studies are needed to clarify the interplay among
      serotonergic system disfunction, suicide, alcohol dependence, impulsivity and the
      role of TPH2 enzyme.

PMID- 21182897
TI  - Effect of body position on bilateral EEG alterations and their relationship with
      autonomic nervous modulation in normal subjects.
AB  - This study investigated the effect of body position on the electroencephalogram
      (EEG) and autonomic nervous modulation, and the relationship between them using
      spectral analysis of EEG and heart rate variability (HRV). All healthy volunteers
      recruited had their electrocardiogram and EEG recorded for power spectral
      analysis. We found that when changing position from supine to upright, the EEG
      spectral components below the alpha band, such as delta and theta bands, were
      significantly decreased while the EEG spectral components above the alpha band,
      such as beta, gamma and omega bands, were significantly increased in both scalps.
      Correlation analysis showed that the theta rhythm of both scalps might be
      associated with the control of HR, the alpha and beta rhythms of right scalp
      might be associated with vagal modulation, and the gamma rhythm of left scalp
      might be associated with sympathetic modulation of the subject. Thus, some EEG
      components might be associated with the autonomic nervous modulation of the
      subject during positional change. There might be a mechanism located in the brain
      stem which jointly controls both autonomic influences on heart rate and EEG
      activation.

PMID- 21182898
TI  - Distribution of AMPA receptor subunits and TARPs in synaptic and extrasynaptic
      membranes of the adult rat nucleus accumbens.
AB  - We characterized the distribution of AMPA receptor (AMPAR) subunits and the
      transmembrane AMPA receptor regulatory proteins (TARPs) gamma-2 and gamma-4 in
      adult rat nucleus accumbens (NAc) using a method that separates plasma membranes
      into synaptic membrane-enriched and extrasynaptic membrane-enriched fractions. We
      also measured GluA1 phosphorylated at serine 845 (pS845 GluA1) and serine 831
      (pS831 GluA1). GluA1-3 protein levels and pS831 GluA1/total GluA1 were higher in
      synaptic membranes. However, pS845 GluA1/total GluA1 was higher in extrasynaptic
      membranes, consistent with a role for S845 phosphorylation in GluA1 insertion at
      extrasynaptic sites. Homeric GluA1 receptors were detected in extrasynaptic
      membranes, consistent with evidence for extrasynaptic Ca(2+)-permeable AMPARs in
      other systems. The TARP gamma-2 was enriched in synaptic membranes, whereas gamma
      4 was mainly found in extrasynaptic membranes, suggesting distinct roles for
      these proteins in the NAc. These experiments provide fundamental information that
      will aid in the interpretation of studies on AMPAR-related plasticity in the NAc.

PMID- 21182899
TI  - Roles of inflammation response in microglia cell through Toll-like receptors
      2/interleukin-23/interleukin-17 pathway in cerebral ischemia/reperfusion injury.
AB  - Microglial activation is one of the causative factors of neuroinflammation in
      cerebral ischemia. Activation via Toll-like receptors (TLRs) causes increased
      proinflammatory cytokine expression, such as interleukin-23 (IL-23) and
      interleukin-17 (IL-17), leading to inflammatory immune responses and neuronal
      damage. In this study, using a rat focal cerebral ischemia reperfusion (IR) model
      and an in vitro oxygen-glucose deprivation reperfusion (OGDR) system, we found
      that TLR2, IL-23 and IL-17 form an axis that leads to increased neuronal
      apoptosis. TLR2 activation results in IL-23 production which stimulates IL-17
      production by microglia. This microglial axis may be a potential therapeutic
      target to control neuroinflammation in brain IR.

PMID- 21182900
TI  - Nickel modulates the electrical activity of cultured cortical neurons through a
      specific effect on N-methyl-D-aspartate receptor channels.
AB  - Nickel (Ni(2+)) is a toxic metal that affects the function of several ionic
      channels. In the N-methyl-d-aspartate (NMDA) subtype of glutamate receptor (NR),
      it causes activity enhancement of the channels containing the NR2B subunit and
      voltage-independent inhibition of those containing NR2A. Thus, it may represent a
      functional marker for the identification of NR native channel subunits. We
      investigated the effect of Ni(2+) on spontaneous NR currents in cortical neurons,
      dissociated from 18-day rat embryos and maintained in culture for up to ~40 days.
      In whole-cell voltage-clamp at -60 mV, in a Mg(2+)-free bath containing the alpha
      amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) antagonist 2,3-dihydroxy-6
      nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX) (10 MUM), spontaneous
      currents were blocked by 10 MUM D(-)-2-Amino-5-phosphonopentanoic acid (APV) (10
      MUM), and by NR2B antagonists, ifenprodil (10 MUM) or Ro25-6981 (Ro25, 1 MUM),
      indicating that they are due to NRs containing predominantly the NR2B subunit. In
      the presence of Ni(2+) (30 MUM) the amplitude and the frequency of spontaneous
      currents were increased and the decay time decreased. A higher dose (300 MUM)
      blocked all electrical activity. In current-clamp, Ni(2+) (30 MUM) caused a ~5 mV
      reversible depolarization. The effect of Ni(2+), as well as that of NR2B
      antagonists, was almost independent of days in vitro (DIV) in the range from 18
      to 33 DIV. The electrical activity of the neuronal networks measured by
      microelectrode arrays (MEAs) was also affected by Ni(2+), which caused a decrease
      in firing rate, but an increase in burst duration, while Ro25 (1-10 MUM) caused a
      decrease in both firing rate and burst duration. Finally, reverse transcription
      polymerase chain reaction (RT-PCR) revealed a predominant expression of NR2B,
      with no modification during DIV. These results demonstrate that, in these
      cultured cells, the NR spontaneous current is almost entirely due by NR2B
      containing receptors and that Ni(2+) affects the electrical activity through a
      specific effect on NR channels.

PMID- 21182902
TI  - High convergence of olfactory and vomeronasal influence in the telencephalon of
      the terrestrial salamander Plethodon shermani.
AB  - Previous work suggested that the telencephalic pathways of the main olfactory and
      vomeronasal systems of vertebrates are mostly isolated from each other, with the
      possible exception of convergence of the two systems into a small part of the
      olfactory amygdala. We tested the hypothesis of convergence between the main
      olfactory and vomeronasal systems by investigating the physiology of
      telencephalic olfactory responses in an in vitro brain preparation of the
      salamander Plethodon shermani. This animal was chosen because its olfactory and
      vomeronasal nerves can be separated and stimulated independently. The nerves were
      stimulated by short current pulses delivered through suction electrodes. Evoked
      field potentials and intracellular responses were systematically recorded in the
      telencephalon. The results showed an abundant overlap of olfactory and
      vomeronasal nerve-evoked field potentials in the ipsilateral lateral
      telencephalon and the amygdala. Single neurons receiving bimodal main olfactory
      and vomeronasal input were found in the dorsolateral telencephalon and amygdala.
      A classification of response latencies suggested that a subset of these neurons
      received direct input from both the main and accessory olfactory bulbs. Unimodal
      excitatory main olfactory responses were mostly found in neurons of the caudal
      telencephalic pole, but were also present in the striato-pallial transition
      area/lateral pallium region and striatum. Unimodal excitatory vomeronasal
      responses were found in neurons of the striato-pallial transition area,
      vomeronasal amygdala, and caudal amygdala. We conclude that the main olfactory
      and vomeronasal systems are extensively integrated within the salamander
      telencephalon and probably act in concert to modulate behavior.

PMID- 21182901
TI  - Overexpression or knockdown of rat tryptophan hyroxylase-2 has opposing effects
      on anxiety behavior in an estrogen-dependent manner.
AB  - Previous studies showed that chronic estrogen treatment increases tryptophan
      hydroxylase-2 (TpH2) mRNA in the caudal dorsal raphe nucleus (DRN), and this
      increase was associated with decreased anxiety. The present study explored the
      interaction of estrogen and targeted, bidirectional manipulation of TpH2
      expression in the caudal DRN by knockdown or viral overexpression, to decrease or
      increase tryptophan hydroxylase expression respectively, on anxiety behavior.
      Rats were ovariectomized and replaced with empty or estradiol capsules (OVX,
      OVX/E, respectively). Animals received microinfusions of either antisense TpH2 or
      control morpholino oligonucleotides into caudal DRN and were later tested in the
      open field test. A separate group of animals were microinfused with TpH2-GFP or
      GFP-only herpes simplex viral vectors into caudal DRN and tested in the open
      field. The bidirectional impact of manipulations on TpH2 expression was confirmed
      using a combination of quantitative protein and mRNA measurements; TpH2
      expression changes were limited to discrete subregions of DRN that were targeted
      by the manipulations. Estradiol decreased anxiety in all behavioral measures. In
      the OVX/E group, TpH2 knockdown significantly decreased time spent in the center
      of the open field, but not in the OVX group, suggesting that TpH2 knockdown
      reduced the anxiolytic effects of estrogen. Conversely, TpH2 overexpression in
      the OVX group mimicked the effects of estrogen, as measured by increased time
      spent in the center of the open field. These results suggest that estrogen and
      TpH2 in the caudal DRN have a critical interaction in regulating anxiety-like
      behavior.

PMID- 21182903
TI  - Gabapentin blocks methamphetamine-induced sensitization and conditioned place
      preference via inhibition of alpha2/delta-1 subunits of the voltage-gated calcium
      channels.
AB  - Our previous investigation demonstrated that repeated administration of morphine
      significantly enhanced alpha(2)/delta-1 subunit expression in the frontal cortex
      and limbic forebrain of mice as well as morphine-induced place preference.
      However, little is known about regulatory mechanisms of alpha(2)/delta-1 subunit
      expression in conditioned place preference by methamphetamine (METH). In the
      present study, we investigated the role of alpha(2)/delta-1 subunit of voltage
      gated calcium channels (VGCCs) in the mouse brain under repeated treatment with
      METH. The level of alpha(2)/delta-1 subunit increased significantly in the limbic
      forebrain including the nucleus accumbens and the frontal cortex of mice showing
      METH-induced sensitization. Under these conditions, the development of behavioral
      sensitization induced by the intermittent administration of METH was
      significantly suppressed by the co-administration of gabapentin (GBP) with
      binding activity to an exofacial epitope of alpha(2)/delta-1 subunit.
      Furthermore, GBP administered i.c.v. caused a dose-dependent inhibition of the
      METH-induced place preference. Chronic GBP treatment at the dose alleviating
      sensitization and place preference significantly reduced the elevation of
      alpha(2)/delta-1 subunit of VGCC induced by the repeated administration of METH
      in the limbic forebrain and frontal cortex, whereas there were no changes in the
      increase of alpha(2)/delta-1 subunit mRNA. These findings indicate that
      alpha(2)/delta-1 subunit plays a critical role in the development of METH-induced
      place preference following neuronal plasticity, and that GBP, which significantly
      suppressed METH-induced place preference by its possible inhibitory action of
      alpha(2)/delta subunit to neuronal membrane, may possibly be used as an
      alternative drug to treat or prevent drug dependence.

PMID- 21182904
TI  - Fast dopamine release events in the nucleus accumbens of early adolescent rats.
AB  - Subsecond fluctuations in dopamine (dopamine transients) in the nucleus accumbens
      are often time-locked to rewards and cues and provide an important learning
      signal during reward processing. As the mesolimbic dopamine system undergoes
      dynamic changes during adolescence in the rat, it is possible that dopamine
      transients encode reward and stimulus presentations differently in adolescents.
      However, to date no measurements of dopamine transients in awake adolescents have
      been made. Thus, we used fast scan cyclic voltammetry to measure dopamine
      transients in the nucleus accumbens core of male rats (29-30 days of age) at
      baseline and with the presentation of various stimuli that have been shown to
      trigger dopamine release in adult rats. We found that dopamine transients were
      detectable in adolescent rats and occurred at a baseline rate similar to adult
      rats (71-72 days of age). However, unlike adults, adolescent rats did not
      reliably exhibit dopamine transients at the unexpected presentation of visual,
      audible and odorous stimuli. In contrast, brief interaction with another rat
      increased dopamine transients in both adolescent and adult rats. While this
      effect habituated in adults at a second interaction, it persisted in the
      adolescents. These data are the first demonstration of dopamine transients in
      adolescent rats and reveal an important divergence from adults in the occurrence
      of these transients that may result in differential learning about rewards.

PMID- 21182905
TI  - Expression of alpha1-adrenoceptors on peripheral nociceptive neurons.
AB  - The purpose of this study was to determine whether alpha(1)-adrenoceptors are
      expressed on primary nociceptive afferents that innervate healthy skin. Skin and
      dorsal root ganglia were collected from adult male Wistar rats and assessed using
      fluorescence immunohistochemistry with antibodies directed against alpha(1)
      adrenoceptors alone or in combination with specific labels including myelin basic
      protein and neurofilament 200 (markers of myelinated nerve fibres), protein gene
      product 9.5 (a pan-neuronal marker), tyrosine hydroxylase (sympathetic neurons),
      isolectin B(4) (IB(4): non-peptidergic sensory neurons), calcitonin gene related
      peptide (CGRP) and transient receptor potential vanilloid receptor 1 (TRPV1)
      (peptidergic sensory neurons). Double labelling in dorsal root ganglia confirmed
      the expression of alpha(1)-adrenoceptors within sub-populations of CGRP, IB(4)
      and TRPV1 immunoreactive neurons. Myelinated and unmyelinated sensory nerve
      fibres in the skin expressed alpha(1)-adrenoceptors whereas sympathetic nerve
      fibres did not. The expression of alpha(1)-adrenoceptors on C- and A-delta
      nociceptive afferent fibres provides a histochemical substrate for direct
      excitation of these fibres by adrenergic agonists. This may help to explain the
      mechanism of sensory-sympathetic coupling that sometimes develops on surviving
      primary nociceptive afferents in neuropathic pain states.

PMID- 21182906
TI  - Comparative genomics uncovers novel structural and functional features of the
      heterotrimeric GTPase signaling system.
AB  - Though the heterotrimeric G-proteins signaling system is one of the best studied
      in eukaryotes, its provenance and its prevalence outside of model eukaryotes
      remains poorly understood. We utilized the wealth of sequence data from recently
      sequenced eukaryotic genomes to uncover robust G-protein signaling systems in
      several poorly studied eukaryotic lineages such as the parabasalids,
      heteroloboseans and stramenopiles. This indicated that the Galpha subunit is
      likely to have separated from the ARF-like GTPases prior to the last eukaryotic
      common ancestor. We systematically identified the structure and sequence features
      associated with this divergence and found that most of the neomorphic positions
      in Galpha form a ring of residues centered on the nucleotide binding site,
      several of which are likely to be critical for interactions with the RGS domain
      for its GAP function. We also present evidence that in some of the potentially
      early branching eukaryotic lineages, like Trichomonas, Galpha is likely to
      function independently of the Gbetagamma subunits. We were able to identify
      previously unknown Ggamma subunits in Naegleria, suggesting that the trimeric
      version was already present by the time of the divergence of the heteroloboseans
      from the remaining eukaryotes. Evolution of Galpha subunits is dominated by
      several independent lineage-specific expansions (LSEs). In most of these cases
      there are concomitant, independent LSEs of RGS proteins along with an
      extraordinary diversification of their domain architectures. The diversity of RGS
      domains from Naegleria in particular, which has the largest complement of Galpha
      and RGS proteins for any eukaryote, provides new insights into RGS function and
      evolution. We uncovered a new class of soluble ligand receptors of bacterial
      origin with RGS domains and an extraordinary diversity of membrane-linked, redox
      associated, adhesion-dependent and small molecule-induced G-protein signaling
      networks that evolved in early-branching eukaryotes, independently of parallel
      systems in animals. Furthermore, this newly characterized diversity of RGS
      domains helps in defining their ancestral conserved interfaces with Galpha and
      also those interfaces that are prone to extensive lineage-specific
      diversification and are thereby responsible for selectivity in Galpha-RGS
      interactions. Several mushrooms show LSEs of Galphas but not of RGS proteins
      pointing to the probable differentiation of Galphas in conjunction with mating
      type diversity. When combined with the characterization of the 7TM receptors
      (GPCRs), it becomes apparent that, through much of eukaryotic evolution, cells
      contained both 7TM receptors that acted as GEFs and those as GAPs (with C
      terminal RGS domains) for Galphas. Only in some lineages like animals and
      stramenopiles the 7TM receptors were restricted to GEF only roles, probably due
      to selection imposed by the rate-constants of the Galphas that underwent lineage
      specific expansion in them. In the alveolate lineage the 7TM receptors occur
      independently of heterotrimeric G-proteins, suggesting the prevalence of G
      protein-independent signaling in these organisms.

PMID- 21182907
TI  - Circadian clock disruption in the mouse ovary in response to 2,3,7,8
      tetrachlorodibenzo-p-dioxin.
AB  - Activation of the aryl hydrocarbon receptor (AhR) by the highly toxic,
      prototypical ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or other dioxin
      like compounds compromises ovarian function by altering follicle maturation and
      steroid synthesis. Although alteration of transcription after nuclear
      translocation and heterodimerization of AhR with its binding partner, aryl
      hydrocarbon nuclear transporter (ARNT), is often cited as a primary mechanism for
      mediating the toxic effects of dioxins, recent evidence indicates that crosstalk
      between AhR and several other signaling pathways also occurs. Like the circadian
      clock genes, AhR is a member of the basic helix-loop-helix, Per-ARNT-SIM (bHLH
      PAS) domain family of proteins. Thus, these studies tested the hypothesis that
      TCDD can act to alter circadian clock regulation in the ovary. Adult female
      c57bl6/J mice entrained to a typical 12h light/12h dark cycle were exposed to a
      single 1 MUg/kg dose of TCDD by gavage. Six days after exposure, animals were
      released into constant darkness and ovaries were collected every 4h over a 24h
      period. Quantitative real-time PCR and immunoblot analysis demonstrated that TCDD
      exposure alters expression of the canonical clock genes, Bmal1 and Per2 in the
      ovary. AhR transcript and protein, which displayed a circadian pattern of
      expression in the ovaries of control mice, were also altered after TCDD
      treatment. Immunohistochemistry studies revealed co-localization of AhR with
      BMAL1 in various ovarian cell types. Furthermore, co-immunoprecipitation
      demonstrated time-of-day dependent interactions of AhR with BMAL1 that were
      enhanced after TCDD treatment. Collectively these studies suggest that crosstalk
      between classical AhR signaling and the molecular circadian clockworks may be
      responsible for altered ovarian function after TCDD exposure.

PMID- 21182908
TI  - Silver nanoparticles induce oxidative cell damage in human liver cells through
      inhibition of reduced glutathione and induction of mitochondria-involved
      apoptosis.
AB  - Silver nanoparticles (AgNPs), which have well-known antimicrobial properties, are
      extensively used in various medical and general applications. Despite the
      widespread use of AgNPs, relatively few studies have been undertaken to determine
      the cytotoxic effects of AgNPs exposure. This study investigates possible
      molecular mechanisms underlying the cytotoxic effects of AgNPs. Here, we show
      that AgNPs-induced cytotoxicity was higher compared than that observed when
      AgNO(3) was used as a silver ion source. AgNPs induced reactive oxygen species
      (ROS) generation and suppression of reduced glutathione (GSH) in human Chang
      liver cells. ROS generated by AgNPs resulted in damage to various cellular
      components, DNA breaks, lipid membrane peroxidation, and protein carbonylation.
      Upon AgNPs exposure, cell viability decreased due to apoptosis, as demonstrated
      by the formation of apoptotic bodies, sub-G(1) hypodiploid cells, and DNA
      fragmentation. AgNPs induced a mitochondria-dependent apoptotic pathway via
      modulation of Bax and Bcl-2 expressions, resulting in the disruption of
      mitochondrial membrane potential (Deltapsi(m)). Loss of Deltapsi(m) was followed
      by cytochrome c release from the mitochondria, resulting in the activation of
      caspases 9 and 3. The apoptotic effect of AgNPs was exerted via the activation of
      c-Jun NH(2)-terminal kinase (JNK) and was abrogated by the JNK-specific
      inhibitor, SP600125 and siRNA targeting JNK. In summary, the results suggest that
      AgNPs cause cytotoxicity by oxidative stress-induced apoptosis and damage to
      cellular components.

PMID- 21182909
TI  - Absence of adverse effect on thyroid function and red blood cells in a population
      of workers exposed to cobalt compounds.
AB  - CONTEXT: Hypothyroidism has been observed in the fifties and sixties as an
      undesirable side-effect of cobalt therapy used for its erythropoietic properties
      in the treatment of anemia. OBJECTIVE: This study aims at evaluating the possible
      impact of both cumulative (long-term) and recent occupational exposure to cobalt
      on thyroid function and red blood cells. METHODS AND SETTING: A cross-sectional
      survey was conducted from February 2008 to August 2009 in a population of 249
      male workers from a cobalt production department in the North of Belgium. The
      possible effect of cobalt exposure on thyroid and red blood cells was
      investigated through multiple regression analyses. RESULTS: Blood cobalt ranged
      from undetectable to 3.20 MUg/100ml (median 0.10); urinary cobalt from 0.30 to
      204.30 MUg/g(creat) (median 3.90) and long-term exposure to cobalt ranged from
      0.15 to 6990.46 MUg/g(creat) . years (median 106.09). No effect of cobalt
      exposure on thyroid or red blood cell parameters was observed at these levels of
      exposure. CONCLUSION: The results support the absence of effects on the thyroid
      and red blood cells when occupational exposure to cobalt is kept below the
      recommended biological limit of occupational exposure (15 MUg Co/g(creat) in
      urine).

PMID- 21182910
TI  - Investigation of properties and recrystallisation behaviour of amorphous
      indomethacin samples prepared by different methods.
AB  - The aim of this study was to investigate if amorphous indomethacin samples,
      prepared using different preparation methods, exhibit different structural and
      kinetic characteristics and if these differences can be correlated to their
      physical stability (time to crystallisation). Samples were prepared by melt
      quenching, spray drying, ball milling, and cryo-milling. The resulting amorphous
      materials were characterised using X-ray diffraction, Raman spectroscopy and
      differential scanning calorimetry. All freshly prepared samples were completely X
      ray amorphous (with a halo being the only feature in the diffractograms). The
      shape of the halos in the diffractograms, however, varied depending on the
      preparation method, suggesting structural variations in the near order of the
      molecules between the differently prepared amorphous forms. Principal component
      analysis of the Raman spectra of the various amorphous forms revealed that the
      samples clustered in the scores plot according to preparation method, again
      suggesting structural differences due to preparation method. The range of
      vibrations associated with the largest spectral differences in the loadings plot
      showed that these differences were due to a range of molecular conformations and
      intermolecular interactions. The ranking of the samples with respect to stability
      was: quench cooled amorphous samples>cryo-milled (alpha-form)>spray dried>ball
      milled (alpha-form)>ball milled (gamma-form)=cryo-milled (gamma-form). This
      ranking was not correlated with the diffractogram shapes or sample distribution
      in the scores plot of the Raman spectra, suggesting that physical stability was
      not directly affected by structural variation in the samples. However, ranking of
      stability of the differently prepared amorphous forms of the drug could be
      predicted by determining the relaxation time values, for all amorphous samples.
      The relaxation times, calculated by using the Adam Gibbs and Kohlrausch-Williams
      Watts equations, were in accordance with the experimentally determined stability
      order. This study showed that correlation of physical stability with calculated
      relaxation time is possible for the same amorphous systems prepared by different
      methods. This could aid in selecting the most appropriate preparation techniques
      in situations where there are a variety of suitable methods.

PMID- 21182911
TI  - Assessment of crystalline disorder in cryo-milled samples of indomethacin using
      atomic pair-wise distribution functions.
AB  - The aim of this study was to investigate the usefulness of the atomic pair-wise
      distribution function (PDF) to detect the extension of disorder/amorphousness
      induced into a crystalline drug using a cryo-milling technique, and to determine
      the optimal milling times to achieve amorphisation. The PDF analysis was
      performed on samples of indomethacin obtained by cryogenic ball milling (cryo
      milling) for different periods of time. X-ray powder diffraction (XRPD),
      differential scanning calorimetry (DSC), polarised light microscopy (PLM) and
      solid state nuclear magnetic resonances (ss-NMR) were also used to analyse the
      cryo-milled samples. The high similarity between the gamma-indomethacin cryogenic
      ball milled samples and the crude gamma-indomethacin indicated that milled
      samples retained residual order of the gamma-form. The PDF analysis encompassed
      the capability of achieving a correlation with the physical properties determined
      from DSC, ss-NMR and stability experiments. Multivariate data analysis (MVDA) was
      used to visualize the differences in the PDF and XRPD data. The MVDA approach
      revealed that PDF is more efficient in assessing the introduced degree of
      disorder in gamma-indomethacin after cryo-milling than MVDA of the corresponding
      XRPD diffractograms. The PDF analysis was able to determine the optimal cryo
      milling time that facilitated the highest degree of disorder in the samples.
      Therefore, it is concluded that the PDF technique may be used as a complementary
      tool to other solid state methods and that further investigations are warranted
      to elucidate the capabilities of this technique.

PMID- 21182912
TI  - Modeling of drug release from bulk-degrading polymers.
AB  - This paper aims to provide a comprehensive review of the various models or
      simulations for predicting drug release from bulk-degrading systems. A brief
      description of bulk degradation processes and factors affecting the degradation
      rate, and consequently the release kinetics, is presented first. Next, several
      important classical models, often used as the basis for subsequent model
      development, are discussed. Both mathematical models and Monte-Carlo based
      simulations have been developed for controlled release from bulk-degrading
      systems. The mathematical models can be further subdivided into two categories.
      First, the diffusion-based models whose transport mechanism is mainly governed by
      diffusion, but with degradation-dependent diffusion coefficients. These are
      generally simpler and easier to use and are sufficient to illustrate mono-phasic
      release. Second, comprehensive models that combine diffusion with other theories
      such as erosion, drug dissolution and/or pore percolations. These models usually
      involve more complex equations but provide good matches for multi-phasic release
      profiles.

PMID- 21182913
TI  - Pharmaceutical applications of non-linear imaging.
AB  - Non-linear optics encompasses a range of optical phenomena, including two- and
      three-photon fluorescence, second harmonic generation (SHG), sum frequency
      generation (SFG), difference frequency generation (DFG), third harmonic
      generation (THG), coherent anti-Stokes Raman scattering (CARS), and stimulated
      Raman scattering (SRS). The combined advantages of using these phenomena for
      imaging complex pharmaceutical systems include chemical and structural
      specificities, high optical spatial and temporal resolutions, no requirement for
      labels, and the ability to image in an aqueous environment. These features make
      such imaging well suited for a wide range of pharmaceutical and biopharmaceutical
      investigations, including material and dosage form characterisation, dosage form
      digestion and drug release, and drug and nanoparticle distribution in tissues and
      within live cells. In this review, non-linear optical phenomena used in imaging
      will be introduced, together with their advantages and disadvantages in the
      pharmaceutical context. Research on pharmaceutical and biopharmaceutical
      applications is discussed, and potential future applications of the technology
      are considered.

PMID- 21182914
TI  - Microscopy imaging of liposomes: from coverslips to environmental SEM.
AB  - A plethora of techniques for the imaging of liposomes and other bilayer vesicles
      are available. However, sample preparation and the technique chosen should be
      carefully considered in conjunction with the information required. For example,
      larger vesicles such as multilamellar and giant unilamellar vesicles can be
      viewed using light microscopy and whilst vesicle confirmation and size prior to
      additional physical characterisations or more detailed microscopy can be
      undertaken, the technique is limited in terms of resolution. To consider the
      options available for visualising liposome-based systems, a wide range of
      microscopy techniques are described and discussed here: these include light,
      fluorescence and confocal microscopy and various electron microscopy techniques
      such as transmission, cryo, freeze fracture and environmental scanning electron
      microscopy. Their application, advantages and disadvantages are reviewed with
      regard to their use in analysis of lipid vesicles.

PMID- 21182915
TI  - In vivo anti-tussive activity and structural features of a polysaccharide
      fraction from water extracted Withania somnifera.
AB  - AIM OF THE STUDY: Anti-tussive drugs are amongst the most widely used medications
      worldwide; however no new class of drugs has been introduced into the market for
      many years. The present study aims at evaluating the structural features and in
      vivo anti-tussive activity of a polysaccharide fraction from water extracted
      Withania somnifera. MATERIALS AND METHODS: Herein, we have analyzed water
      extracted material of Withania somnifera using chemical, chromatographic,
      spectroscopic and biological methods. RESULTS: A polysaccharide fraction (F3)
      containing arabinosyl, galactosyl and galacturonosyl residues were obtained by
      anion exchange chromatography of the water extracted material. This polymer is
      branched and contained (1,5)-/(1,3,5)-linked arabinofuranosyl, (1,3)-/(1,6)
      /(1,3,6)-linked galactopyranosyl residues together with small amount of terminal
      rhamnopyranosyl and terminal arabinofuranosyl residues. Peroral administration of
      this pectic arabinogalactan in a dose of 50 mg kg(-1) body weight (b.w.)
      decreased the number of cough efforts induced by citric acid in guinea pigs like
      that of codeine. CONCLUSIONS: This study provides a scientific basis for the past
      and present ethnomedical uses of this plant.

PMID- 21182916
TI  - Cho-kyung-jong-ok-tang, a traditional Korean herbal formula induces type 2 shift
      in murine natural killer cell cytokine production.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cho-kyung-jong-ok-tang (CKJOT) is a traditional
      Korean herbal formula specifically used for female infertility including
      unexplained recurrent pregnancy loss (RPL). AIM OF THE STUDY: The present study
      aims to evaluate the effects of CKJOT on mouse natural killer (NK) cells to
      address the possible immunological basis of protective effects of this herbal
      medicine on unexplained RPL. MATERIALS AND METHODS: NK cells isolated from
      spleens of 6-week-old C57BL/6 mice were differentiated into NK0, NK1, and NK2
      cells in the presence of various concentrations of CKJOT-extract. Apoptotic cell
      number, level of intracellular cytokines, and expression of cytokine-related
      transcription factors were measured. RESULTS: CKJOT had little effect in
      improving viability of NK0, NK1, and NK2 cells. However, CKJOT addition during NK
      cell differentiation suppressed the production of interferon-gamma (IFN-gamma),
      and enhanced that of interleukin-5, in the NK1 and NK2 subsets, respectively. T
      bet, a transcription factor associated with IFN-gamma expression was down
      regulated; while Th2 linked transcription factors (STAT6 and GATA3) were up
      regulated especially with 100 MUg/mL treatment of CKJOT. CONCLUSION: The type 2
      shift in NK cell-secreted cytokines induced by CKJOT in mouse NK cells may
      explain the protective effect associated with its traditional use in unexplained
      RPL.

PMID- 21182917
TI  - Euonymus alatus extract attenuates LPS-induced NF-kappaB activation via IKKbeta
      inhibition in RAW 264.7 cells.
AB  - AIM OF THE STUDY: The present study was performed to investigate the underlying
      mechanisms of anti-inflammatory effects with the extract of Euonymus alatus
      (EEA), and specially focused on nuclear factor kappaB (NF-kappaB) signaling
      pathway by targeting the IkappaB kinase beta (IKKbeta). MATERIALS AND METHODS:
      The effect of EEA for IKKbeta activity was analyzed using an immobilized metal
      affinity for phosphochemicals (IMAP)-based time-resolved fluorescence resonance
      energy transfer (TR-FRET) assay. The effect of EEA on lipopolysaccharide (LPS)
      induced NF-kappaB activation in murine macrophage RAW 264.7 cells with western
      blotting and immunofluorescent staining was evaluated. RESULTS: IKKbeta studies
      based on IMAP-TR-FRET showed that EEA possesses a potent IKKbeta inhibitory
      activity with IC(50) value of 11.83MUg/ml. EEA (10, 30MUg/ml) also attenuated the
      LPS-induced IkappaBalpha phosphorylation/degradation, NF-kappaB translocation and
      subsequent NO synthesis in RAW 264.7 cells. CONCLUSIONS: These results suggest
      that EEA abrogates LPS-induced NF-kappaB signaling pathway by targeting the
      IKKbeta in RAW 264.7 cells and these properties may provide a molecular basis for
      understanding the inhibitory effects of EEA on LPS-mediated inflammation.

PMID- 21182918
TI  - Gastric antisecretory and antiulcer activities of Cedrus deodara (Roxb.) Loud. in
      Wistar rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cedrus deodara (Roxb.) Loud. is used in Ayurvedic
      medicine to treat peptic ulcer. AIM OF THE STUDY: To evaluate the gastric
      antisecretory and antiulcer activity of Cedrus deodara. MATERIALS AND METHODS:
      The volatile oil extracted by steam distillation of Cedrus deodara wood was
      examined for its gastric antisecretory and antiulcer effect in the pylorus
      ligated rat model and ethanol induced gastric lesions in rats. RESULTS: The
      volatile oil showed significant antisecretory activity as evidenced by decreased
      gastric fluid volume, total acidity, free acidity and increase in the pH of the
      gastric fluid in pylorus-ligated rats. Our studies also revealed that
      pretreatment with Cedrus deodara significantly reduced the number of ulcer, ulcer
      score and ulcer index in pylorus-ligated and ethanol treated rats. The antiulcer
      activity of Cedrus deodara is further supported by histopathological study which
      showed protection of mucosal layer from ulceration and inflammation. CONCLUSION:
      The present findings conclude that volatile oil of Cedrus deodara wood has potent
      antisecretory and antiulcer effects and justify the traditional usage of this
      herb to treat peptic ulcers.

PMID- 21182919
TI  - Anti-osteoporotic activity of aqueous-methanol extract of Berberis aristata in
      ovariectomized rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally Berberis aristata is employed for
      its supposed properties in treatment of joint pain and also used in alleviating
      symptoms of menopause. AIM OF THE STUDY: The aim of the present study is to
      evaluate the antiosteoporotic effect of Berberis aristata in ovariectomized (OVX)
      rats. MATERIALS AND METHODS: Sprague-Dawley rats were divided into sham and OVX
      groups. The OVX rats were further divided into four groups, which received
      standard estrogen (0.0563 mg/kg) and 100, 300, and 500 mg/kg aqueous-methanol
      extract of Berberis aristata, daily for 42 days. The uterine weight, bone loss,
      ash content, biomechanical, biochemical and histopathological observation were
      carried out for antiosteoporotic activity. RESULTS: The experimental animals
      treated with Berberis aristata aqueous-methanol extract showed dose dependent
      activity. The significant increase in uterine weight, femur BMD, ash content and
      lumbar hardness were observed. In addition, increased levels of calcium and
      phosphorus in serum and significant decreased in urine were observed as compared
      to control OVX group. The histopathological results also confirm the protective
      effect of extract. CONCLUSION: The present findings strongly suggest that
      Berberis aristata possess the potent antiosteoporosis activity in ovariectomized
      rats and substantiates the ethnic use in treatment of postmenopausal
      osteoporosis.

PMID- 21182920
TI  - Role of Syzygium cumini seed extract in the chemoprevention of in vivo genomic
      damage and oxidative stress.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: [corrected] The seeds of Syzygium cumini, Skeels
      (Jamun) are extensively used in India for treatment of diabetes and other
      ailments. AIM OF THE STUDY: The aim of this work was to assess the role of Jamun
      seed extract (JSE) as a chemoprotective agent against in vivo oxidative stress
      and genomic damage. MATERIALS AND METHODS: Experiments were carried out to
      evaluate in vitro protective effects of JSE against hydroxyl radical induced
      damage in pBR322 DNA, and in vivo genomic damage and oxidative stress in mice
      which received JSE orally for 5 days before exposure to genotoxic carcinogens
      urethane (URE) and 7,12-dimethyl benz(a)anthracene (DMBA). RESULTS: Aqueous and
      ethanolic extracts of JSE showed significant protective effects against hydroxyl
      radical induced strand breaks in pBR322 DNA. The in vivo experiments with aqueous
      JSE showed significant protective effects against chromosomal damage induced by
      the genotoxic carcinogens URE and DMBA. Biochemical assays registered significant
      inhibition of hepatic lipid peroxidation and increase in GSH level and activity
      of GST, SOD and CAT. CONCLUSION: Our findings suggest that JSE can possibly play
      an important role as a chemopreventive agent against oxidative stress and genomic
      damage.

PMID- 21182921
TI  - Anti-inflammatory and antinociceptive properties of the leaves of Eriobotrya
      japonica.
AB  - AIM OF THE STUDY: The leaves of Eriobotrya japonica Lindl. have been widely used
      as a traditional medicine for the treatment of many diseases including coughs and
      asthma. The present study was designed to validate the anti-inflammatory and
      antinociceptive properties of the n-BuOH fraction of E. japonica (LEJ) leaves.
      MATERIALS AND METHODS: The anti-inflammatory properties of LEJ were studied using
      IFN-gamma/LPS activated murine peritoneal macrophage model. The antinociceptive
      effects of LEJ were assessed using experimental models of pain, including thermal
      nociception methods, such as the tail immersion test and the hotplate test, and
      chemical nociception induced by intraperitoneal acetic acid and subplantar
      formalin in mice. To examine the possible connection of the opioid receptor to
      the antinociceptive activity of LEJ, we performed a combination test with
      naloxone, a nonselective opioid receptor antagonist. RESULTS: In the IFN-gamma
      and LPS-activated murine peritoneal macrophage model, LEJ suppressed NO
      production and iNOS expression via down-regulation of NF-kappaB activation. It
      also attenuated the expression of COX-2 and the secretion of pro-inflammatory
      cytokines like TNF-alpha and IL-6. Moreover, LEJ also demonstrated strong and
      dose-dependent antinociceptive activity compared to tramadol and indomethacin in
      various experimental pain models. In a combination test using naloxone,
      diminished analgesic activities of LEJ were observed, indicating that the
      antinociceptive activity of LEJ is connected with the opioid receptor.
      CONCLUSIONS: The results indicate that LEJ had potent inhibitory effects on the
      inflammatory mediators including nitric oxide, iNOS, COX-2, TNF-alpha and IL-6
      via the attenuation of NF-kappaB translocation to the nucleus. LEJ also showed
      excellent antinociceptive activity in both central and peripheral mechanism as a
      weak opioid agonist. Based on these results, LEJ may possibly be used as an anti
      inflammatory and an analgesic agent for the treatment of pains and inflammatory
      diseases.

PMID- 21182922
TI  - Effect of Phellodendron amurense in protecting human osteoarthritic cartilage and
      chondrocytes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional medicine has been widely using
      Phellodendron amurense Rupr. (Rutaceae) to treat various inflammatory diseases
      including arthritis. AIM OF THE STUDY: This study investigated the effects of
      Phellodendron amurense in protecting cartilage, including regulating the levels
      of aggrecanases, matrix metalloproteinases (MMPs)/tissue inhibitor of
      metalloproteinase (TIMP), proinflammatory cytokines and signaling of the mitogen
      activated protein kinase (MAPK) pathway in human osteoarticular cartilage and
      chondrocytes. MATERIALS AND METHODS: Explants from human osteoarthritis cartilage
      were cultured alone or in IL-1alpha for 7 days with or without Phellodendron
      amurense ethanol extract or celecoxib (40, 100, 200MUg/ml). The effect of
      Phellodendron amurense on matrix degradation induced by IL-1alpha in human
      articular cartilage was assessed by staining, and the quantities of sulfated
      glycosaminoglycan (GAG) and type II collagen were calculated from the culture
      media. The levels of aggrecanases, MMPs, TIMP, and PGE(2) in the culture media
      were investigated using an enzyme-linked immunosorbent assay (ELISA). In
      addition, reverse transcription polymerase chain reaction (RT-PCR) evaluated the
      mRNA expression of aggrecanases, MMPs and TIMP. Furthermore, Western blot
      analysis was performed to identify the roles that Phellodendron amurense played
      in the ERK, JNK and p38 signaling pathways. RESULTS: Phellodendron amurense
      showed no evident cytotoxicity on human articular cartilage. Phellodendron
      amurense significantly inhibited the IL-1alpha-induced degradation of GAG and
      type II collagen from human osteoarticular cartilage in a concentration-dependent
      manner. Celecoxib did not significantly inhibit IL-1alpha-induced release of GAG
      and only slightly reduced type II collagen. Phellodendron amurense also dose
      dependently decreased the levels of aggrecanase-1 and -2, MMP-1, -3, and -13,
      whereas it increased TIMP-1 expression in human osteoarticular cartilage.
      Celecoxib only decreased MMP-1 and MMP-13 levels in human osteoarticular
      cartilage. In addition, Phellodendron amurense reduced the phosphorylation of
      extracellular signal regulated kinase (ERK)1/2, Jun NH2-terminal kinase (JNK) and
      activated phospho-p38 MAPK in a dose-dependent manner in human osteoarthritic
      chondrocytes. CONCLUSIONS: Phellodendron amurense inhibited osteoarticular
      cartilage and chondrocyte destruction by inhibiting proteoglycan release and type
      II collagen degradation, down-regulating aggrecanases, MMP activities and phospho
      ERK1/2, JNK and p38 MAP kinase signaling, and up-regulating TIMP-1 activity.
      Therefore, our results suggest that Phellodendron amurense is a potential
      therapeutic agent to protect cartilage against OA progression.

PMID- 21182923
TI  - Anti-biofilm activity of TanReQing, a Traditional Chinese Medicine used for the
      treatment of acute pneumonia.
AB  - AIM OF THE STUDY: TanReQing (TRQ) is a Traditional Chinese Medicine used to treat
      biofilm related upper respiratory infections. However, its anti-biofilm mechanism
      remains unknown. The aim of this study is to investigate the anti-biofilm
      activity of TRQ and to compare it with penicillin in vitro. MATERIALS AND
      METHODS: The effect of TRQ and penicillin on free state, biofilm formation and
      mature biofilms of Staphylococcus aureus was studied using the crystal violet and
      the XTT reduction assays. Confocal Laser Scanning Microscopy was used to generate
      the 3D-transmission-fluorescence images of drug treated Staphylococcus aureus
      biofilms. RESULTS: The in vitro data showed that TRQ is less effective than
      penicillin in eradicating the planktonic bacteria. However, the anti-biofilm
      activity of TRQ is different from that of penicillin. TRQ not only does inhibit
      the formation of the Staphylococcus aureus biofilm, but also kills the viable
      cells embed in Staphylococcus aureus biofilm matrix. CONCLUSIONS: This study
      shows for the first time that TRQ possesses an antibiotic activity against
      biofilm bacteria. This activity is different from that of penicillin. The
      evaluation system applied in this study can be utilized for identifying new anti
      biofilm products from Traditional Chinese Medicine.

PMID- 21182924
TI  - Anti-inflammatory activity of Terminalia paniculata bark extract against acute
      and chronic inflammation in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Terminalia paniculata Roxb. (Family-Combretaceae)
      is a wild tree commonly used in traditional ayurvedic medicine for the treatment
      of inflammation of parotid glands and in menstrual disorders. AIM OF THE STUDY:
      To explore the folk use of Terminalia paniculata on pharmacological grounds to
      evaluate the scientific basis of anti-inflammatory activity. MATERIALS AND
      METHODS: The anti-inflammatory activity of Terminalia paniculata was studied
      against carrageenan-induced hind paw edema, air pouch inflammation and complete
      Freund's adjuvant (CFA)-induced arthritis in rats. The aqueous extract of
      Terminalia paniculata bark (TPW) was administered at the concentrations of 100,
      200 and 400mg/kg body weight. RESULTS: TPW showed significant (p<0.05) anti
      inflammatory activity by reducing the edema volume in carrageenan-induced paw
      edema in rats. Further, TPW (400mg/kg) also reduced the carrageenan-induced
      leukocyte migration (50.92 +/- 5.71%) and myeloperoxidase activity (49.31 +/-
      5.24%) in air pouch exudates. TPW (200mg/kg) exhibits anti-rheumatic and
      analgesic activities by improving the altered haematological milieu (ESR, CRP,
      RF, WBC, RBC and Hb) and also by inhibiting the flexion scores and radiographic
      changes in CFA-induced arthritis. This extract also had significant (p<0.05)
      effects on the occurrence of secondary lesions compared to CFA control.
      CONCLUSIONS: Terminalia paniculata bark may be a potential preventive or
      therapeutic candidate for the treatment of chronic inflammation and arthritis.

PMID- 21182925
TI  - Antidiabetic effect of Symplocos cochinchinensis (Lour.) S. Moore. in type 2
      diabetic rats.
AB  - AIM: Symplocos cochinchinensis (Lour.) S. Moore. is used in Indian system of
      traditional medicine to treat diabetes mellitus. The present study aims to
      investigate the antidiabetic efficacy of the hexane extract of Symplocos
      cochinchinensis leaves in high fat diet-low streptozotocin (STZ) induced type 2
      diabetic rats. MATERIALS AND METHODS: The doses for the study were fixed based on
      Irwin test. The hypoglycemic effect of the hexane extract of Symplocos
      cochinchinensis leaves were studied in normal rats. Oral glucose and insulin
      tolerance tests were carried out. The antihyperglycemic effect of the hexane
      extract at 250 and 500 mg/kg was studied in high fat diet-low STZ induced type 2
      diabetic rats for 28 days. RESULTS: The extracts showed no adverse effects up to
      5 g/kg concentration. In hypoglycemic study, after treatment with hexane extract
      at 250 and 500 mg/kg the blood glucose was mildly reduced. In oral glucose
      tolerance test, the treatment with the hexane extract at 250 and 500 mg/kg showed
      a highly significant reduction of 12.07% and 23.58% in plasma glucose levels,
      respectively 30 min after glucose load. The insulin tolerance test also showed
      improved insulin sensitivity after 60 min of insulin treatment. In high fat diet
      low STZ induced type 2 diabetic rats, after 28 days treatment with the hexane
      extract at 250 and 500 mg/kg reduced the plasma glucose level by 17.04% and
      42.10%, respectively. A significant reduction in plasma insulin, plasma and
      hepatic total cholesterol (TC), triglycerides (TG) and free fatty acids (FFA) and
      a significant increase in liver glycogen were observed in treated diabetic rats.
      CONCLUSION: This study demonstrated the potential antidiabetic property of hexane
      extract of Symplocos cochinchinensis leaves on type 2 diabetes mellitus, thus
      justifying its traditional usage.

PMID- 21182927
TI  - Further development of the NCTC 2544 IL-18 assay to identify in vitro contact
      allergens.
AB  - Several European Union legislations request the use of in vitro methods for
      toxicological evaluations, including sensitization, in order to increase consumer
      safety but also to reduce the use of animals. The EU project SENS-IT-IV addresses
      the need of developing predictive in vitro tests to assess contact and
      respiratory hypersensitivity reactions. In this context, we have recently
      reported the possibility to use IL-18 production in the human keratinocyte cell
      line NCTC 2544 to discriminate contact sensitizer from irritants and low
      molecular weight respiratory allergens. The aims of the present study were to
      further develop this assay in order to optimize experimental conditions; to
      develop a 96-well plate format to establish a high throughput assay; to test the
      performance of other available keratinocyte cell lines, and to understand the
      signal transduction pathway involved in p-phenylenediamine (PPD)-induced IL-18
      production. If cells reach confluence at the moment of treatment, the ability to
      identify contact allergens is lost; therefore a careful check for the optimal
      cell density using PPD as reference contact allergen is critical. In our hands, a
      cell density of 1-2.5 * 10(5)cells/ml gave optimal stimulation. In order to
      develop a high throughput test, cells seeded in 96-well plate were exposed to
      contact allergens (2,4-dinitrochlorobenzene, p-phenylenediamine, isoeugenol,
      cinnamaldehyde, tetramethylthiuram disulfite, resorcinol, cinnamic alcohol and
      eugenol), irritants (phenol, sodium laurel sulphate, lactic acid and salicylic
      acid) and respiratory allergens (hexachloroplatinate, diphenylmethane
      diisocyanate, trimellitic anhydride). A selective increase in total
      (intracellular plus released) IL-18 was observed 24h later in cells treated with
      contact allergens, whereas no changes were observed following treatment with
      respiratory allergens and irritants, confirming previous results obtained in a 24
      well format assay. A selective induction of IL-18 was also obtained testing with
      PPD other keratinocyte cell lines, namely HPKII and HaCaT, with the HPKII showing
      the highest stimulation index. Regarding the signal transduction pathway, we
      could demonstrate using selective inhibitors a role for oxidative stress, NF
      kappaB and p38 MAPK activation in PPD-induced IL-18 production. In conclusion,
      results obtained suggest that the production of IL-18 represents a promising
      endpoint for the screening of potential contact allergens. The assay can be
      performed in a 96-well plate format, different keratinocyte cell lines can be
      used, and a role for oxidative stress in contact allergen-induced IL-18 was
      demonstrated.

PMID- 21182926
TI  - Deep insights into Dictyocaulus viviparus transcriptomes provides unique
      prospects for new drug targets and disease intervention.
AB  - The lungworm, Dictyocaulus viviparus, causes parasitic bronchitis in cattle, and
      is responsible for substantial economic losses in temperate regions of the world.
      Here, we undertake the first large-scale exploration of available transcriptomic
      data for this lungworm, examine differences in transcription between different
      stages/both genders and identify and prioritize essential molecules linked to
      fundamental metabolic pathways, which could represent novel drug targets.
      Approximately 3 million expressed sequence tags (ESTs), generated by 454
      sequencing from third-stage larvae (L3s) as well as adult females and males of D.
      viviparus, were assembled and annotated. The assembly of these sequences yielded
      ~61,000 contigs, of which relatively large proportions encoded collagens (4.3%),
      ubiquitins (2.1%) and serine/threonine protein kinases (1.9%). Subtractive
      analysis in silico identified 6928 nucleotide sequences as being uniquely
      transcribed in L3, and 5203 and 7889 transcripts as being exclusive to the adult
      female and male, respectively. Most peptides predicted from the conceptual
      translations were nucleoplasmins (L3), serine/threonine protein kinases (female)
      and major sperm proteins (male). Additional analyses allowed the prediction of
      three drug target candidates, whose Caenorhabditis elegans homologues were linked
      to a lethal RNA interference phenotype. This detailed exploration, combined with
      future transcriptomic sequencing of all developmental stages of D. viviparus,
      will facilitate future investigations of the molecular biology of this parasitic
      nematode as well as genomic sequencing. These advances will underpin the
      discovery of new drug and/or vaccine targets, focused on biotechnological
      outcomes.

PMID- 21182928
TI  - Hormone levels are associated with clinical markers and cytokine levels in human
      localized cutaneous leishmaniasis.
AB  - Leishmaniasis is a serious health problem in several parts of the world, and
      localized cutaneous leishmaniasis (LCL) is the most frequent presentation of the
      tegumentary form of this disease cluster. Clinical presentations of leishmaniasis
      are influenced by both parasite and host factors, with emphasis on the host
      immune response. Alterations in plasma hormone levels have been described in many
      infections, and changes in hormone levels could be related to an imbalanced
      cytokine profile. In the present work, we evaluated a group of patients with LCL
      to determine changes in plasma hormone levels (cortisol, DHEA-S, estradiol,
      prolactin and testosterone) and their association with clinical markers of
      disease (lesion size, dose used to reach cure and time to cure) and with
      cytokines produced by PBMC stimulated by SLA (IFN-gamma, IL-10 and TNF-alpha).
      Individuals with LCL exhibited lower plasma levels of DHEA-S, prolactin and
      testosterone compared with sex-matched controls, whereas levels of cortisol and
      estradiol were similar between patients and controls. Plasma levels of cortisol,
      estradiol or prolactin positively correlated with at least one clinical
      parameter. Cortisol and prolactin levels exhibited a negative correlation with
      levels of IFN-gamma, whereas no correlation was observed with IL-10 or TNF-alpha
      levels. A decrease in DHEA-S levels was observed in male LCL patients when
      compared to male healthy controls. No other differences between the sexes were
      observed. Our results indicate a role for neuroendocrine regulation that
      restricts Th1 responses in human LCL. It is possible that, although impairing
      parasite killing, such neuroimmunomodulation may contribute to limiting tissue
      damage.

PMID- 21182929
TI  - Brain homeostasis is maintained by "danger" signals stimulating a supportive
      immune response within the brain's borders.
AB  - An organism's behavior is determined by the way it senses and perceives the
      surrounding environment, and by its responses to these stimuli. The major factors
      known to affect the behavioral response to an event are genetic background,
      environmental factors, and past experiences, and their imprinting on the relevant
      brain circuits. Recently, circulating immune cells were introduced as novel
      players into this system. It was proposed that the brain and circulating immune
      cells engage in a continuous dialogue that takes place within the brain's
      territory, though outside the parenchyma (occurring within the brain's borders -
      the choroid plexi, the brain meninges and the cerebrospinal fluid (CSF)). The
      cytokines secreted by activated leukocytes residing at the borders were shown to
      affect neurotrophic factors production within the parenchyma. Here, we suggest
      that such a dialogue is stimulated at the brain's borders, upon need, by a
      "danger" signal that originates in the parenchyma in response to any
      destabilizing event, and discuss the potential role of reactive oxygen species
      (ROS) in transmitting this signal. Accordingly, a failure to restore balance is
      likely to lead to aberrant responses to subsequent events. This view thus
      supports the contention that circulating immune cells are required to maintain
      the brain's balanced activity and suggests a novel mechanism whereby the
      surveying immune cells are sensing the brain's status and needs.

PMID- 21182931
TI  - Teratogenic potential of tribenoside, a drug for the treatment of haemorrhoids
      and varicose veins--a population-based case--control study.
AB  - Tribenoside is used for the treatment of haemorrhoids and varicose veins,
      frequently in pregnant women as well, but published data regarding its possible
      teratogenic effect are not available. Thus the risk of congenital abnormalities
      (CAs) was estimated in cases of pregnant women with oral tribenoside treatment
      (TT) in the Hungarian Case-Control Surveillance System of Congenital
      Abnormalities. Of 22,843 cases with CA, 174 (0.76%), while of 38,151 matched
      controls without CA, 285 (0.75%) were born to mothers with TT. There was no
      higher risk for total CAs after TT during any time of pregnancy but congenital
      hydrocephaly had a higher risk after medically recorded TT in the second and/or
      third month of pregnancy, i.e. critical period of this CA. In conclusion TT in
      pregnant women associated with a higher risk of congenital hydrocephalus in their
      children, however, this finding is based on only 4 cases therefore requires
      further confirmation in future studies.

PMID- 21182930
TI  - Cancer induces inflammation and depressive-like behavior in the mouse: modulation
      by social housing.
AB  - Considerable data demonstrate a high prevalence of depressive symptoms in cancer
      patients. This study introduces an experimental model to examine the effect of
      tumor on depressive-like behavior. Female C57BL/6 mice were injected i.p. with
      syngeneic ID8 ovarian carcinoma. Experiment 1 measured sucrose intake before and
      after tumor incubation to assess the effect of tumor on anhedonic depressive-like
      behavior. Experiment 2 examined effects of tumor and social housing on anhedonia
      and a second depressive-like behavior, tail suspension test (TST) immobility.
      Systemic proinflammatory and antiinflammatory cytokines were measured following
      each experiment. Additional behaviors assessed the specificity of tumor's effect
      on depressive-like behavior. Tumor caused a reduction in sucrose intake relative
      to baseline and control levels (P<.05). Moreover, individually-housed tumor
      bearing mice exhibited a lower sucrose preference than group-housed tumor-bearing
      or control mice in either housing condition (P<.05). Although tumor-bearing mice
      exhibited less locomotion than controls (P<.001), there was no significant effect
      of tumor on TST immobility. Tumor caused higher levels of systemic
      proinflammatory and antiinflammatory cytokines and smaller body weight (P<.05),
      but appetite and motor capacity were not significantly affected. Statistical
      mediation analysis showed that circulating interleukin-6 partially mediated the
      effect between tumor and home cage locomotion (P<.01) but not between tumor and
      sucrose intake. It is concluded that tumor elicits anhedonic depressive-like
      behavior in a murine model of ovarian cancer. This may have important
      implications for etiology of depression in the clinical cancer setting.

PMID- 21182932
TI  - Elevated dietary intake of Zn-methionate is associated with increased sperm DNA
      fragmentation in the boar.
AB  - Boars fed on ration of 200 ppm Zn methionate showed a significant increase (P <
      0.001) in sperm DNA fragmentation when compared to animals fed on non
      supplemented and rations containing 150 ppm Zn methionate. There was a positive
      correlation (R2 = 0.207; P = 0.002) between % sperm DNA fragmentation (SDF) and
      the concentration of Zn in spermatozoa. Increased Zn in the diet also resulted in
      a non-proportional increase in Zn concentration in the testis and spermatozoa but
      not in the epididymis; Zn in sperm accumulated at levels up to 50 times higher
      than that found in the seminal plasma and 10-13 times that found in the
      epididymis and testis, respectively. These results show that supplementation of
      dietary Zn at a concentration of 200 ppm had an adverse effect on boar sperm DNA
      quality and may be related to the ability of spermatozoa to accumulate Zn during
      spermiogenesis.

PMID- 21182933
TI  - Effect of in utero and lactational nicotine exposure on the male reproductive
      tract in peripubertal and adult rats.
AB  - The objective of this study was to determine the effect of in utero and
      lactational exposure to nicotine on the male reproductive tract. Dams were
      randomly assigned to receive saline or nicotine bitartrate (1mg/kg-d s.c.) daily
      for two weeks prior to mating until weaning (postnatal day 21). Male offspring
      were sacrificed at 7 (peri-pubertal) and 26 (adult) weeks of age. Nicotine
      exposure resulted in retention of spermatids after stage VIII, tubular
      vacuolation, degeneration of pachytene and round spermatids at stage VII in the
      testes; and lymphocyte infiltration, germ cell exfoliation, and hypospermia in
      epididymides, at 7 weeks of age. Nicotine-exposure had no effect on testis or
      epididymal morphology, daily sperm production, epididymal sperm reserve, sperm
      viability at 26 weeks of age, and circulating testosterone levels at either age
      examined. We conclude that maternal nicotine-exposure during pregnancy and
      lactation can induce transient structural changes in the testis and epididymis of
      male offspring.

PMID- 21182934
TI  - Effect of perinatal and postnatal bisphenol A exposure to the regulatory circuits
      at the hypothalamus-pituitary-gonadal axis of CD-1 mice.
AB  - Bisphenol A (BPA) is used in the manufacture of many products and is ubiquitous
      in the environment. Adverse effects of BPA on animal reproductive health have
      been reported, however most of the studies relied on the approaches in the
      assessment of conventional histology and anatomical features. The mechanistic
      actions of BPA are not clear. In the present study, a murine model was used to
      study potential effects of BPA exposure during perinatal and postnatal periods on
      endocrine functions of hypothalamic-pituitary-gonadal (HPG)-axis. At the
      hypothalamic-pituitary level, BPA exposure resulted in the up-regulation of the
      expression levels of KiSS-1, GnRH and FSH mRNA in both male and female pups. At
      the gonadal levels, BPA caused inhibition in the expressions of testicular
      steroidogenic enzymes and the synthesis of testosterone in the male pups.
      Conversely exposure to BPA resulted in a greater aromatase expression level and
      the synthesis of estrogen in the female pups. BPA is a weak estrogen agonist and
      its effects reported on animal studies are difficult to reconcile with
      mechanistic action of estrogen. In this study we hypothesized that the effects of
      BPA on reproductive dysfunction may be due to its actions on gonadal
      steroidogenesis and so the anomalous releases of endogenous steroid hormones.
      This non-ER-mediated effect is more potent in affecting the feedback regulatory
      circuits in the HPG-axis.

PMID- 21182935
TI  - Aldose reductase in keratinocytes attenuates cellular apoptosis and senescence
      induced by UV radiation.
AB  - Although aldose reductase (AR) has been implicated in the cellular response to
      oxidative stress, the role of AR in ultraviolet-B (UVB)-induced cellular injury
      has not been investigated. Here, we show that an increased expression of AR in
      human keratinocytes modulates UVB-induced apoptotic cell death and senescence.
      Overexpression of AR in HaCaT cells significantly attenuated UVB-induced cellular
      damage and apoptosis, with a decreased generation of reactive oxygen species
      (ROS) and aldehydes. Ablation of AR with small interfering RNA or inhibition of
      AR activity abolished these effects. We also show that increased AR activity
      suppressed UVB-induced activation of the p38 and c-Jun N-terminal kinases, but
      did not affect the extracellular signal-regulated kinase and phosphatidylinositol
      3-kinase pathways. Similarly, UVB-induced translocation of Bax and Bcl-2 to
      mitochondria and cytosol, respectively, was markedly attenuated in cells
      overexpressing AR. Knockdown or inhibition of AR activity in primary cultured
      keratinocytes enhanced UVB-induced cellular senescence and increased the level of
      a cell-cycle regulatory protein, p53. Finally, cellular apoptosis induced by UVB
      radiation was significantly reduced in the epidermis of transgenic mice
      overexpressing human AR. These findings suggest that AR plays an important role
      in the cellular response to oxidative stress by sequestering ROS and reactive
      aldehydes generated in keratinocytes.

PMID- 21182936
TI  - Point mutated caveolin-3 form (P104L) impairs myoblast differentiation via Akt
      and p38 signalling reduction, leading to an immature cell signature.
AB  - Unbalanced levels of caveolin-3 (Cav3) are involved in muscular disorders. In the
      present study we show that differentiation of immortalized myoblasts is affected
      by either lack or overexpression of Cav3. Nevertheless, depletion of Cav3 induced
      by delivery of the dominant-negative Cav3 (P104L) form elicited a more severe
      phenotype, characterized by the simultaneous attenuation of the Akt and p38
      signalling networks, leading to an immature cell and molecular signature.
      Accordingly, differentiation of myoblasts harbouring Cav3 (P104L) was improved by
      countering the reduced Akt and p38 signalling network via administration of IGF-1
      or trichostatin A. Furthermore, loss of Cav3 correlated with a deregulation of
      the TGF-beta-induced Smad2 and Erk1/2 pathways, confirming that Cav3 controls TGF
      beta signalling at the plasma membrane. Overall, these data suggest that loss of
      Cav3, primarily causing attenuation of both Akt and p38 pathways, contributes to
      impair myoblast fusion.

PMID- 21182937
TI  - Antimicrobial activity of ruthenium-based intercalators.
AB  - Multidrug resistance of bacterial pathogens is a major problem and there is a
      clear need for the development of new types of antibiotics. Here we investigated
      the antimicrobial activity of ruthenium(II) based DNA-intercalating complexes.
      These complexes were found to have no activity in vitro against the Gram-negative
      bacterium Escherichia coli, but the complexes were clearly active against the
      Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus. In vivo
      activity has also been demonstrated for one of the compounds using a simple
      infection model, the nematode Caenorhabditis elegans. Importantly, this also
      showed that the compound tested was not toxic to the nematodes.

PMID- 21182938
TI  - Influence of atorvastatin on the pharmacokinetics and pharmacodynamics of
      glyburide in normal and diabetic rats.
AB  - Atorvastatin is a selective HMG-CoA reductase competitive inhibitor, used for the
      treatment of hyperlipidaemia. It is metabolized by CYP 3A4 and 3A5 isoenzymes in
      liver. It also has moderate inhibition on metabolizing enzymes like CYP 2C9, 2D6
      and 3A4. Hence there is more possibility of atorvastatin for inhibition of
      metabolism of glyburide, by both CYP 2C9 and 3A4. We have studied the effects of
      atorvastatin on the pharmacodynamics and pharmacokinetics of glyburide in
      experimental diabetic rats. Atorvastatin (20mg/kg p.o.) was given to alloxan
      induced diabetic rats for 7 consecutive days followed by glyburide (10mg/kg
      p.o.). In the rats co-treated with atorvastatin and glyburide, fasting plasma
      glucose concentration (60.69+/-5.70%) was further reduced, markedly as compared
      with glyburide-treated animals. In co-treated group, the pharmacokinetic
      parameters like clearance (27.83+/-3.55l/h) of glyburide was reduced, while peak
      plasma concentration (18.39+/-5.29MUg/ml), area under the plasma concentration
      time curve (120.02+/-15.17MUg/ml/h) and elimination half-life (4.09+/-0.50h) were
      significantly increased when compared to glyburide alone administered rats. The
      results of this study revealed that atorvastatin led to the PK/PD changes have
      been due to glyburide increased bioavailability, decrease volume of distribution,
      and/or decrease total clearance may be due to the inhibition of cytochrome P450
      metobolic system.

PMID- 21182939
TI  - Design and evaluation of novel pH-sensitive chitosan nanoparticles for oral
      insulin delivery.
AB  - Chitosan nanoparticles (CS NPs) have been commonly regarded as potential carriers
      for the mucosal delivery of therapeutic peptides because of their
      biocompatibility, bioadhesion and permeation enhancing properties. However, they
      have limited colloidal stability and readily dissociate and dissolve in the
      acidic gastric conditions. In the current study, CS NPs were formulated by ionic
      cross-linking with hydroxypropyl methylcellulose phthalate (HPMCP) as a pH
      sensitive polymer and evaluated for the oral delivery of insulin. In vitro
      results revealed a superior acid stability of CS/HPMCP NPs with a significant
      control over insulin release and degradation in simulated acidic conditions with
      or without pepsin. Furthermore, fluorescently-labeled CS/HPMCP NPs showed a 2- to
      4-fold improvement in the intestinal mucoadhesion and penetration compared to
      CS/TPP NPs as evidenced by quantitative fluorescence analysis and confocal
      microscopy. After s.c. injection to rats, no significant difference in the
      hypoglycemic effect of insulin solution or insulin-loaded CS/HPMCP NPs was
      observed, confirming the physico-chemical stability and biological activity of
      the entrapped peptide. Following peroral administration, CS/HPMCP NPs increased
      the hypoglycemic effect of insulin by more than 9.8 and 2.8-folds as compared to
      oral insulin solution and insulin-loaded CS/tripolyphosphate (TPP) NPs,
      respectively.

PMID- 21182940
TI  - Influence of polyunsaturated fatty acids on Cortisol transport through MDCK and
      MDCK-MDR1 cells as blood-brain barrier in vitro model.
AB  - Transport across the blood-brain barrier is a relevant factor in the
      pharmacological action of many drugs and endogenous substances whose action site
      is located in brain. An overactive P-gp has been suggested to be of relevance for
      the resistance of the HPA system to be suppressed by glucocorticoids, which is
      one of the best described biological abnormalities in certain types of
      depression. PUFA acids have shown clinical efficacy in depressed patients and the
      hypothesis is that these compounds are able to reduce HPA axis activity as this
      effect has been shown in animal models of depression. The objective of the
      present work was (1) to characterize Cortisol transport through MDCK and MDCK
      MDR1 cell lines (as in vitro models of the BBB) to confirm its transport
      mechanism as substrate of P-gp and (2) to evaluate the effect of PUFA acids as
      enhancers of Cortisol transport in the BBB model and explore the enhancement
      mechanism. Transport studies of Cortisol were performed in both directions, from
      apical-to-basolateral and from basolateral-to-apical sides. The in vitro
      experiments showed that Cortisol transport is concentration dependent and it is
      affected by several transporters (absorption and secretion processes). The
      results indicate that PUFA acids increase Cortisol transport in the BBB models
      but not through the inhibition of P-gp efflux but thanks to membrane
      fluidification and some effect on tight junction integrity.

PMID- 21182942
TI  - Effects of mild processing pressures on the performance of dry powder inhaler
      formulations for inhalation therapy. 1: Budesonide and lactose.
AB  - Batch-to-batch variability, whereby distinct batches of dry powder inhaler
      formulations, though manufactured with identical components and specifications,
      may exhibit significant variations in aerosol performance, is a major obstacle to
      consistent and reproducible drug delivery for inhalation therapy. This
      variability may arise from processing or manufacturing effects that have yet to
      be investigated. This study focused on the potential effects of mild compression
      forces experienced during powder manufacture and transport (such as during the
      filling of, or storage in, a hopper) on the flowability and aerosol performance
      of a lactose-based dry powder inhaler formulation. Different grades of inhalation
      lactose were subjected to typical compression forces by either placing a weight
      of known mass on the sample or by using a Texture Analyzer to apply a constant
      force while measuring the distance of compaction. Powder flowability was
      evaluated with a rotating drum apparatus by imaging the avalanching of the powder
      over time. The average avalanche angle and avalanche time were used to determine
      the flowability of each sample, both before and after compression treatment.
      Aerosol performance of treated and untreated lactose/budesonide blends (2% (w/w))
      was assessed in dispersion studies using a next generation impactor. At
      compression forces in excess of 5 kPa, the flowability of milled lactose was
      decreased relative to the untreated sample. Compression of lactose prior to
      blending caused a decrease in in vitro aerosol dispersion performance. However,
      dispersion performance was unchanged when compression occurred subsequent to drug
      blending. In contrast, inhalation grade sieved lactose, differing from the milled
      grade with a lower concentration of lactose fines (<10 MUm) and larger overall
      particle sizes, exhibited no statistical differences in either flowability or
      dispersion performance across all experimental treatments. Thus, the compression
      of the lactose fines onto the surfaces of the larger lactose particles due to
      mild processing pressures is hypothesized to be the cause of these observed
      performance variations. It was shown that simulations of storage and transport in
      an industrial scale hopper can induce significant variations in formulation
      performance, and it is speculated that this could be a source of batch-to-batch
      variations.

PMID- 21182943
TI  - Examination of drug release and distribution from drug-eluting stents with a
      vessel-simulating flow-through cell.
AB  - The recently introduced vessel-simulating flow-through cell offers new
      possibilities to examine the release from drug-eluting stents in vitro. In
      comparison with standard dissolution methods, the additional compartment allows
      for the examination of distribution processes and creates dissolution conditions
      which simulate the physiological situation at the site of implantation. It was
      shown previously that these conditions have a distinct influence on the release
      rate from the stent coating. In this work, different preparation techniques were
      developed to examine the spatial distribution within the compartment simulating
      the vessel wall. These methods allowed for the examination of diffusion depth and
      the distribution resulting in the innermost layer of the compartment simulating
      the vessel wall. Furthermore, the in vitro release and distribution examined
      experimentally were modelled mathematically using finite element (FE) methods to
      gain further insight into the release and distribution behaviour. The FE
      modelling employing the experimentally determined diffusion coefficients yielded
      a good general description of the experimental data. The results of the modelling
      also provided important indications that inhomogeneous coating layer thicknesses
      around the strut may result from the coating process which influence release and
      distribution behaviour. Taken together, the vessel-simulating flow-through cell
      in combination with FE modelling represents a unique method to analyse drug
      release and distribution from drug-eluting stents in vitro with particular
      opportunities regarding the examination of spatial distributions within the
      vessel-simulating compartment.

PMID- 21182941
TI  - Relationship between the size of nanoparticles and their adjuvant activity: data
      from a study with an improved experimental design.
AB  - There is a growing interest in identifying the relationship between the size of
      nanoparticles and their adjuvant activity, but the results from recent studies
      remain controversial. To address the controversy, it was thought that one should
      pay attention to the nanoparticle formulations to make sure that the antigen
      loaded nanoparticles to be compared are not only different in particle size, but
      more importantly, as identical to each other as possible in all other formulation
      properties. In the present study, using ovalbumin (OVA) as a model antigen
      conjugated onto nanoparticles engineered from lecithin/glyceryl monostearate-in
      water emulsions, we prepared OVA-nanoparticles of 230 nm and 708 nm. Before
      evaluating the immune responses induced by them in a mouse model, we made sure
      that: (i) the sizes of the two OVA-nanoparticles did not extensively overlap,
      (ii) the nanoparticles have similar zeta potentials and comparable antigen
      loading, and (iii) the nanoparticles did not aggregate when suspended in
      simulated biological media. We then showed that when subcutaneously injected into
      mice, the 230 nm OVA-conjugated nanoparticles induced stronger OVA-specific
      antibody and cellular immune responses than the 708 nm OVA-nanoparticles. Future
      studies attempting to correlate the size of nanoparticles and their adjuvant
      activities need to consider formulation parameters to ensure that the particles
      are different only in size and are stable before and after injection.

PMID- 21182944
TI  - Contribution to the development of inhibitors of 17beta-hydroxysteroid
      dehydrogenase types 1 and 7: key tools for studying and treating estrogen
      dependent diseases.
AB  - 17beta-Hydroxysteroid dehydrogenases (17beta-HSDs) belong to a group of key
      enzymes involved in the biosynthesis of steroidal hormones by catalyzing the
      reduction of 17-ketosteroids or the oxidation of 17beta-hydroxysteroids. From
      three members known in the early nineties, the 17beta-HSD functional family has
      grown to 15 members over the last 20 years. This growing number of 17beta-HSD
      isoforms questioned the importance of each member, especially in their
      implication in estrogen- and androgen-dependent diseases, such as breast and
      prostate cancers. One of the strategies used to address the physiological
      importance of 17beta-HSDs is to use potent and selective inhibitors. Furthermore,
      enzyme inhibitors could also be of therapeutic interest by reducing the level of
      estradiol (E2). Focusing on estrogens, we targeted 17beta-HSD types 1 and 7, two
      enzymes able to transform the weak estrogen estrone (E1) into the potent estrogen
      E2. The present review article gives a description of different classes of
      inhibitors of 17beta-HSD1 (C6-derivatives of E2, C16-derivatives of E2 as
      alkylating and dual action compounds, E2-adenosine hybrids, E2-simplified
      adenosine hybrids, and C16-derivatives of E1 or E2) and of inhibitors of 17beta
      HSD7, all these inhibitors developed in our laboratory. The chemical structures
      and inhibitory activity of these steroidal inhibitors, their potential as
      therapeutic agents, and their use as tools to elucidate the role of these enzymes
      in particular biological systems will be discussed. Article from the Special
      issue on Targeted Inhibitors.

PMID- 21182945
TI  - 1,25-dihydroxyvitamin D3 and a superagonistic analog in combination with
      paclitaxel or suberoylanilide hydroxamic acid have potent antiproliferative
      effects on anaplastic thyroid cancer.
AB  - Anaplastic thyroid cancer represents one of the most aggressive cancers. The
      active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), has been
      shown to have antiproliferative and/or redifferentiating properties in several
      malignancies, including thyroid cancer. The objective of this study was to
      investigate the effects of 1,25(OH)(2)D(3) and the superagonistic analog CD578 in
      anaplastic thyroid cancer, alone or in combination with paclitaxel, a taxane, and
      suberoylanilide hydroxamic acid (SAHA), a potent histone deacetylase inhibitor
      with promising effects in undifferentiated thyroid cancer. Four human thyroid
      cancer cell lines (FTC-133, C643, 8505C and HTh74) were treated with
      1,25(OH)(2)D(3) or CD578, alone or in combination with paclitaxel or SAHA.
      Effects on cell growth and differentiation were evaluated. Clear effects on
      growth arrest were observed in a clonogenic assay, and absolute cell counts
      demonstrated a 24-36% reduction in all cell lines after 72h treatment with
      1,25(OH)(2)D(3) (10(-6)M) and a 60% inhibition after 120h in the most sensitive
      cell line HTh74. A similar growth inhibition was shown after treatment with a
      1000-fold lower concentration of analog CD578. This growth arrest was explained
      by antiproliferative effects, further supported by an increased % of cells in the
      G(0)-G(1) phase of the cell cycle and by a decreased transcription factor E2F1
      mRNA expression. Combination treatments of 1,25(OH)(2)D(3) or CD578 with
      paclitaxel or SAHA resulted in an additive and in some conditions a synergistic
      effect on the inhibition of proliferation. Redifferentiation analysis revealed
      only a modest increase in sodium iodide symporter and thyroglobulin mRNA
      expression after treatment with 1,25(OH)(2)D(3), without additive effect after
      combination treatment. No effects were observed on TSH-receptor or thyroid
      peroxidase mRNA expression. Our in vitro findings demonstrate that the
      superagonistic vitamin D analog CD578 holds promise as adjuvant antiproliferative
      therapy of anaplastic thyroid cancer, especially in combination with other drugs
      such as paclitaxel or SAHA.

PMID- 21182946
TI  - Before or after does it matter? Different protocols of environmental enrichment
      differently influence motor, synaptic and structural deficits of cerebellar
      origin.
AB  - Cerebellar compensation is a reliable model of lesion-induced plasticity
      occurring through profound synaptic and neurochemical modifications in cortical
      and sub-cortical regions. As the recovery from cerebellar deficits progresses,
      the firstly enhanced glutamate striatal transmission is then normalized. The time
      course of cerebellar compensation and the concomitant striatal modifications
      might be influenced by protocols of environmental enrichment (EE) differently
      timed in respect to cerebellar lesion. In the present study, we analyzed the
      effects of different EE protocols on postural and locomotor behaviors (by means
      of a neurological rating scale), and on striatal synaptic activity (by means of
      recordings of spontaneous glutamate-mediated excitatory postsynaptic currents
      (sEPSCs)) and on morphological correlates (by means of density and dendritic
      length of Fast Spiking (FS) interneurons) following hemicerebellectomy (HCb) in
      rats. Cerebellar motor deficits were reduced faster in the enriched animals in
      comparison to standard housed HCbed rats. The beneficial influence of EE was
      higher in the animals enriched before the HCb than in rats enriched only after
      the lesion. In parallel, the HCb-induced increase in striatal sEPSCs was not
      observed in rats enriched before HCb and attenuated in rats enriched after HCb.
      Furthermore, the EE prevented the shrinkage of dendritic arborization of FS
      striatal interneurons. Also this effect was more marked in animals enriched
      before than after the HCb. The exposure to EE exerted either neuro-protective or
      therapeutic actions on the cerebellar deficits. The experience-dependent changes
      of the synaptic and neuronal connectivity observed in the striatal neurons may
      represent one of the mechanisms through which the enrichment facilitates
      functional compensation following the cerebellar damage.

PMID- 21182947
TI  - Clinical studies on the management of periodontal diseases utilizing
      subantimicrobial dose doxycycline (SDD).
AB  - Periodontitis, the most common chronic inflammatory condition known to mankind,
      is a disease that results in the destruction of tooth supporting tissues.
      Periodontitis is initiated by a bacterial biofilm on the tooth surface below the
      gingival margin. Until fairly recently it was assumed that the bacteria were the
      primary cause of tissue destruction, however, a large body of research has
      revealed that it is the patient's immune response that is actually responsible
      for the majority of the breakdown of tooth supporting tissues. Contemporary
      thinking suggests that successful, long term management of chronic periodontitis
      may combine both local mechanical and antimicrobial strategies to reduce the
      microbial bio-burden along with modulation of the host, patient's excessive,
      immuno-inflammatory response to the bacterial exposure known as host modulatory
      therapy (HMT). Based on extensive literature documenting the enzymatic inhibition
      and related anti-inflammatory properties of the tetracyclines, a new drug was
      developed as a host modulatory agent and approved by the United States Food and
      Drug Administration (FDA) for use as an adjunct to conventional scaling and root
      planing for the treatment of chronic periodontitis. A subantimicrobial dose of
      doxycycline (SDD) at 20 mg (Periostat((r))) has been found to be a safe and
      effective adjunct when taken twice daily for at least 3 months and up to 24
      months in randomized placebo controlled clinical trials. Periostat((r)) is
      currently the only FDA approved inhibitor of the matrix metalloproteinases
      implicated in the plaque-induced pathologic degradation of connective tissue
      collagen of the periodontal supporting structures. This review paper begins with
      a brief description of the disease process known as periodontitis followed by an
      extensive review of the Phase I-IV clinical trial data that established the
      safety and efficacy of sub-antimicrobial dose doxycycline (SDD) as an adjunct to
      scaling and root planing for the treatment of periodontitis.

PMID- 21182949
TI  - Processing-dependent trafficking of Sonic hedgehog to the regulated secretory
      pathway in neurons.
AB  - Neurons are an important source of the secreted morphogen Sonic hedgehog (Shh),
      however, little is known about neuron-specific regulation of Shh transport and
      secretion. To study this process, we investigated the subcellular distribution of
      Shh in primary neurons and differentiated cells of a neuroendocrine cell line by
      fluorescence microscopy and biochemical fractionation. In retinal ganglion cells,
      endogenous Shh was distributed as intra- and extracellular puncta at the soma,
      dendrites, axons and neurite terminals. Shh(+) puncta move bidirectionally and
      colocalize with markers of synaptic vesicles (SVs) and dense core granules. Lipid
      modification and proteolysis were required for Shh sorting to SVs and cell
      surface association. Finally, consistent with its association with regulated
      secretory vesicles, Shh secretion could be induced under depolarizing conditions.
      Taken together, these observations suggest that long-range Shh transport and
      signalling in neurons involves trafficking to the regulated secretory pathway and
      cell surface accumulation of Shh on axons and suggests a link between neuronal
      activity and Shh release.

PMID- 21182950
TI  - The protective effect of enteric glial cells on intestinal epithelial barrier
      function is enhanced by inhibiting inducible nitric oxide synthase activity under
      lipopolysaccharide stimulation.
AB  - Enteric glial cells (EGC) play an essential role in maintaining the integrity of
      intestinal epithelial barrier (IEB). However, the mechanism of EGCs in the
      regulation of IEB functions under lipopolysaccharide (LPS) stimulation is
      unknown. To investigate the barrier-related role of EGCs in response to the LPS
      challenge, the coculture model of EGCs and intestinal epithelial cells (IEC) IEC
      6 was established in vitro. Transepithelial resistance (TER) measurements showed
      that, LPS treatment significantly increased barrier permeability of IEC monolayer
      from the basolateral side (35.4+/-6.3 Omega/cm(2), p<0.05) but not the apical
      side (69.7+/-6.3 Omega/cm(2)) when compared with the control group (81.8+/-10.9
      Omega/cm(2)). The assessment of intestinal epithelial integrity by TER reading
      and by measuring expression of tight junction protein revealed that, incubation
      with EGCs or EGC conditioned media significantly increased the TER of IEC
      monolayers under normal condition as well as the LPS stimulation, accompanied
      with upregulating zonula occludens-1 and occludin expression at mRNA and protein
      levels. Real-time quantitative polymerase chain reaction and nitric production
      assay demonstrated that LPS exposure elicited a maximally 13-fold increase of
      inducible nitric oxide synthase (iNOS) mRNA expression and 10-fold increase of
      nitric oxide production of EGCs. After being pretreated with the selective iNOS
      inhibitor 1400 W, EGCs significantly increased the TER of IEC monolayers against
      the disruption effect of LPS (p<0.05). These findings suggest that EGCs play an
      important role in maintaining the IEB function in response to the LPS
      stimulation. The protective effect of EGCs on IEB functions could be enhanced by
      inhibiting the increase of iNOS activity induced by LPS.

PMID- 21182948
TI  - Beta-catenin signaling, liver regeneration and hepatocellular cancer: sorting the
      good from the bad.
AB  - Among the adult organs, liver is unique for its ability to regenerate. A
      concerted signaling cascade enables optimum initiation of the regeneration
      process following insults brought about by surgery or a toxicant. Additionally,
      there exists a cellular redundancy, whereby a transiently amplifying progenitor
      population appears and expands to ensure regeneration, when differentiated cells
      of the liver are unable to proliferate in both experimental and clinical
      scenarios. One such pathway of relevance in these phenomena is Wnt/beta-catenin
      signaling, which is activated relatively early during regeneration mostly through
      post-translational modifications. Once activated, beta-catenin signaling drives
      the expression of target genes that are critical for cell cycle progression and
      contribute to initiation of the regeneration process. The role and regulation of
      Wnt/beta-catenin signaling is now documented in rats, mice, zebrafish and
      patients. More recently, a regenerative advantage of the livers in beta-catenin
      overexpressing mice was reported, as was also the case after exogenous Wnt-1
      delivery to the liver paving the way for assessing means to stimulate the pathway
      for therapeutics in liver failure. beta-Catenin is also pertinent in hepatic oval
      cell activation and differentiation. However, aberrant activation of the Wnt/beta
      catenin signaling is reported in a significant subset of hepatocellular cancers
      (HCC). While many mechanisms of such activation have been reported, the most
      functional means of aberrant and sustained activation is through mutations in the
      beta-catenin gene or in AXIN1/2, which encodes for a scaffolding protein critical
      for beta-catenin degradation. Intriguingly, in experimental models hepatic
      overexpression of normal or mutant beta-catenin is insufficient for
      tumorigenesis. In fact beta-catenin loss promoted chemical carcinogenesis in the
      liver due to alternate mechanisms. Since most HCC occur in the backdrop of
      chronic hepatic injury, where hepatic regeneration is necessary for maintenance
      of liver function, but at the same time serves as the basis of dysplastic
      changes, this Promethean attribute exhibits a Jekyll and Hyde behavior that makes
      distinguishing good regeneration from bad regeneration essential for targeting
      selective molecular pathways as personalized medicine becomes a norm in clinical
      practice. Could beta-catenin signaling be one such pathway that may be redundant
      in regeneration and indispensible in HCC in a subset of cases?

PMID- 21182952
TI  - Association of adenoma detection rate with the risk of interval cancer.

PMID- 21182951
TI  - Schwannomin/merlin promotes Schwann cell elongation and influences myelin segment
      length.
AB  - The Neurofibromatosis type 2 tumor suppressor, schwannomin (Sch) is a plasma
      membrane-cytoskeleton linking protein that regulates receptor signaling and actin
      dynamics. We examined Sch's role in specifying morphological changes needed for
      Schwann cell (SC) function in vitro. Isolated Sch-GFP-expressing SCs extended
      bipolar processes 82% longer than those formed by GFP-expressing cells. In
      contrast, SCs expressing dominant negative Sch-BBA-GFP extended bipolar processes
      16% shorter than controls and 64% shorter than Sch-GFP-expressing SCs. nf2 gene
      inactivation caused isolated mouse SCs to transition from bipolar to multipolar
      cells. Live imaging revealed that SCs co-expressing Sch-GFP and dominant negative
      RacN17 behaved similarly in dorsal root ganglion explant cultures; they quickly
      aligned on axons and slowly elongated bipolar processes. In contrast, SCs
      expressing constitutively active RacV12 underwent continuous transitions in
      morphology that interfered with axon alignment. When co-cultured with neurons
      under myelin-promoting conditions, Sch-GFP-expressing SCs elaborated longer
      myelin segments than GFP-expressing SCs. In contrast, Sch-BBA-GFP-expressing SCs
      failed to align on or myelinate axons. Together, these results demonstrate that
      Sch plays an essential role in inducing and/or maintaining the SC's spindle shape
      and suggest that the mechanism involves Sch-dependent inhibition of Rac activity.
      By stabilizing the bipolar morphology, Sch promotes the alignment of SCs with
      axons and ultimately influences myelin segment length.

PMID- 21182953
TI  - Hepatic adenomas caused by somatic HNF1A mutations in children with biallelic
      mismatch repair gene mutations.

PMID- 21182954
TI  - A rare cause of bloody stools in a 57-year-old woman with hepatocellular
      carcinoma.

PMID- 21182955
TI  - Obscure gastrointestinal bleeding for 10 years in a 31-year-old man.

PMID- 21182956
TI  - Endoscopic balloon dilation: the panacea for Crohn's strictures?

PMID- 21182957
TI  - Large retroperitoneal mass in a young female patient.

PMID- 21182958
TI  - The Walkerton outbreak revisited at year 8: predictors, prevalence, and prognosis
      of postinfectious irritable bowel syndrome.

PMID- 21182960
TI  - Mucosal gene expression signatures that predict response of ulcerative colitis to
      infliximab.

PMID- 21182962
TI  - Esophageal polypoid mass in a 78-year-old woman.

PMID- 21182963
TI  - Structural insights into the high affinity binding of cardiotonic steroids to the
      Na+,K+-ATPase.
AB  - The Na+,K+-ATPase belongs to the P-ATPase family, whose characteristic property
      is the formation of a phosphorylated intermediate. The enzyme is also a defined
      target for cardiotonic steroids which inhibit its functional activity and
      initiate intracellular signaling. Here we describe the 4.6 A resolution crystal
      structure of the pig kidney Na+,K+-ATPase in its phosphorylated form stabilized
      by high affinity binding of the cardiotonic steroid ouabain. The steroid binds to
      a site formed at transmembrane segments alphaM1-alphaM6, plugging the ion pathway
      from the extracellular side. This structure differs from the previously reported
      low affinity complex with potassium. Most importantly, the A domain has rotated
      in response to phosphorylation and alphaM1-2 move towards the ouabain molecule,
      providing for high affinity interactions and closing the ion pathway from the
      extracellular side. The observed re-arrangements of the Na+,K+-ATPase stabilized
      by cardiotonic steroids may affect protein-protein interactions within the
      intracellular signal transduction networks.

PMID- 21182964
TI  - Precise beam-tilt alignment and collimation are required to minimize the phase
      error associated with coma in high-resolution cryo-EM.
AB  - Electron microscopy at a resolution of 0.4nm or better requires more careful
      adjustment of the illumination than is the case at a resolution of 0.8nm. The use
      of current-axis alignment is not always sufficient, for example, to avoid the
      introduction of large phase errors, at higher resolution, due to axial coma. In
      addition, one must also ensure that off-axis coma does not corrupt the data
      quality at the higher resolution. We particularly emphasize that the standard CTF
      correction does not account for the phase error associated with coma. We explain
      the cause of both axial coma and the typically most troublesome component of off
      axis coma in terms of the well-known shift of the electron diffraction pattern
      relative to the optical axis that occurs when the illumination is not parallel to
      the axis. We review the experimental conditions under which coma causes
      unacceptably large phase errors, and we discuss steps that can be taken when
      setting up the conditions of illumination, so as to ensure that neither axial nor
      off-axis coma is a problem.

PMID- 21182965
TI  - Differential expression of LvHSP60 in shrimp in response to environmental stress.
AB  - Previous studies showed that heat-shock protein 60 (HSP60) was known to function
      as a molecular chaperone and is an important factor in the innate immune system
      in mammals. However, little was known about the physiological relevance of HSP60
      in marine invertebrates. This study focuses on long-term monitoring of the
      differential expression of LvHSP60 in shrimp Litopenaeus vannamei in response to
      environmental stress. The thermal aggregation assay elucidated that LvHSP60 was
      an effective chaperone. It also suggested that LvHSP60 may employ the cell's
      intrinsic mechanism to start the immunizing process. Using quantitative real-time
      PCR to monitor gene expression showed that LvHSP60 was variable under different
      stresses including environmental stress and pathogenic infection. LvHSP60 was
      speculated to regulate the adaptive responses to overcome environmental stresses.
      In conclusion, our study proved that LvHSP60 plays an important role in the
      intrinsic immune system and stress responses of shrimp.

PMID- 21182966
TI  - Effects of problem size and arithmetic operation on brain activation during
      calculation in children with varying levels of arithmetical fluency.
AB  - Most studies on mathematics learning in the field of educational neuroscience
      have focused on the neural correlates of very elementary numerical processing
      skills in children. Little is known about more complex mathematical skills that
      are formally taught in school, such as arithmetic. Using functional magnetic
      resonance imaging, the present study investigated how brain activation during
      single-digit addition and subtraction is modulated by problem size and arithmetic
      operation in 28 children aged 10-12 years with different levels of arithmetical
      fluency. Commensurate with adult data, large problems and subtractions activated
      a fronto-parietal network, including the intraparietal sulci, the latter of which
      indicates the influence of quantity-based processes during procedural strategy
      execution. Different from adults, the present findings revealed that particularly
      the left hippocampus was active during the solution of those problems that are
      expected to be solved by means of fact retrieval (i.e. small problems and
      addition), suggesting a specific role of the hippocampus in the early stages of
      learning arithmetic facts. Children with low levels of arithmetical fluency
      showed higher activation in the right intraparietal sulcus during the solution of
      problems with a relatively small problem size, indicating that they continued to
      rely to a greater extent on quantity-based strategies on those problems that the
      children with relatively higher arithmetical fluency already retrieved from
      memory. This might represent a neural correlate of fact retrieval impairments in
      children with mathematical difficulties.

PMID- 21182967
TI  - fMRI item analysis in a theory of mind task.
AB  - Conventional analyses of functional magnetic resonance imaging (fMRI) data
      compare the brain's response to stimulus categories (e.g., pictures of faces,
      stories about beliefs) across participants. In order to infer that effects
      observed with the specific items (a particular set of pictures or stories) are
      generalizable to the entire population (all faces, or all stories about beliefs),
      it is necessary to perform an "item analysis." Item analyses may also reveal
      relationships between secondary (non-hypothesized) features of the items and
      functional activity. Here, we perform an item analysis on a set of stories
      commonly used for localizing brain regions putatively involved in Theory of Mind
      (ToM): right and left temporo-parietal junction (RTPJ/LTPJ), precuneus (PC),
      superior temporal sulcus (STS) and medial prefrontal cortex (MPFC). We address
      the following questions: Do brain regions that comprise the ToM network respond
      reliably across items (i.e. different stories about beliefs)? Do these brain
      regions demonstrate reliable preferences for items within the category? Can we
      predict any region's response to individual items, by using other features of the
      stimuli? We find that the ToM network responds reliably to stories about beliefs,
      generalizing across items as well as subjects. In addition, several regions in
      the ToM network have reliable preferences for individual items. Linguistic
      features of the stimuli did not predict these item preferences.

PMID- 21182968
TI  - Complex span tasks and hippocampal recruitment during working memory.
AB  - The working memory (WM) system is vital to performing everyday functions that
      require attentive, non-automatic processing of information. However, its
      interaction with long term memory (LTM) is highly debated. Here, we used fMRI to
      examine whether a popular complex WM span task, thought to force the displacement
      of to-be-remembered items in the focus of attention to LTM, recruited medial
      temporal regions typically associated with LTM functioning to a greater extent
      and in a different manner than traditional neuroimaging WM tasks during WM
      encoding and maintenance. fMRI scans were acquired while participants performed
      the operation span (OSPAN) task and an arithmetic task. Results indicated that
      performance of both tasks resulted in significant activation in regions typically
      associated with WM function. More importantly, significant bilateral activation
      was observed in the hippocampus, suggesting it is recruited during WM encoding
      and maintenance. Right posterior hippocampus activation was greater during OSPAN
      than arithmetic. Persitimulus graphs indicate a possible specialization of
      function for bilateral posterior hippocampus and greater involvement of the left
      for WM performance. Recall time-course activity within this region hints at LTM
      involvement during complex span.

PMID- 21182969
TI  - Single-subject classification of schizophrenia by event-related potentials during
      selective attention.
AB  - BACKGROUND: Executive dysfunction has repeatedly been proposed as a robust and
      promising substrate of analytical approaches in the research of neurocognitive
      markers of schizophrenia. Here, we present a mixed model- and data-driven
      classification approach by applying a task that targets executive dysfunction in
      schizophrenia and by investigating relevant event-related potential (ERP)
      features with machine learning classifiers. METHODS: Forty schizophrenic patients
      and forty matched healthy controls completed the Attention Network Test while an
      electroencephalogram was recorded. Target-locked N1 and P3 ERP components were
      constructed and submitted to different classification analyses without a priori
      hypotheses. Standardized source localization was applied to estimate neural
      sources of N1 and P3 deficits in schizophrenia. RESULTS: We obtained a
      classification accuracy of 79% using only very few ERP components. Central P3
      components following compatible and incompatible trials and right parietal N1
      latencies averaged across targets and were sufficient for classification. P3
      deficits were associated with anterior cingulate cortex dysfunction, while right
      posterior current density deficits were observed in schizophrenia during the N1
      time frame. CONCLUSIONS: The data exemplarily show how automated inference may be
      applied to classify a pathological state in single subjects without prior
      knowledge of their diagnoses. While classification accuracy may be optimized by
      application of other executive paradigms, this approach illustrates the potential
      of machine learning algorithms for the identification of biomarkers that are
      independent of clinical assessments. Conversely, data suggest a
      pathophysiological mechanism that includes early visual and late executive
      deficits during response inhibition in schizophrenia.

PMID- 21182970
TI  - DTI measures in crossing-fibre areas: increased diffusion anisotropy reveals
      early white matter alteration in MCI and mild Alzheimer's disease.
AB  - Though mild cognitive impairment is an intermediate clinical state between
      healthy aging and Alzheimer's disease (AD), there are very few whole-brain voxel
      wise diffusion MRI studies directly comparing changes in healthy control, mild
      cognitive impairment (MCI) and AD subjects. Here we report whole-brain findings
      from a comprehensive study of diffusion tensor indices and probabilistic
      tractography obtained in a very large population of healthy controls, MCI and
      probable AD subjects. As expected from the literature, all diffusion indices
      converged to show that the cingulum bundle, the uncinate fasciculus, the entire
      corpus callosum and the superior longitudinal fasciculus are the most affected
      white matter tracts in AD. Significant differences between MCI and AD were
      essentially confined to the corpus callosum. More importantly, we introduce for
      the first time in a degenerative disorder an application of a recently developed
      tensor index, the "mode" of anisotropy, as well as probabilistic crossing-fibre
      tractography. The mode of anisotropy specifies the type of anisotropy as a
      continuous measure reflecting differences in shape of the diffusion tensor
      ranging from planar (e.g., in regions of crossing fibres from two fibre
      populations of similar density or regions of "kissing" fibres) to linear (e.g.,
      in regions where one fibre population orientation predominates), while
      probabilistic crossing-fibre tractography allows to accurately trace pathways
      from a crossing-fibre region. Remarkably, when looking for whole-brain diffusion
      differences between MCI patients and healthy subjects, the only region with
      significant abnormalities was a region of crossing fibres in the centrum
      semiovale, showing an increased mode of anisotropy. The only white matter region
      demonstrating a significant difference in correlations between neuropsychological
      scores and a diffusion measure (mode of anisotropy) across the three groups was
      the same region of crossing fibres. Further examination using probabilistic
      tractography established explicitly and quantitatively that this previously
      unreported increase of mode and co-localised increase of fractional anisotropy
      was explained by a relative preservation of motor-related projection fibres (at
      this early stage of the disease) crossing the association fibres of the superior
      longitudinal fasciculus. These findings emphasise the benefit of looking at the
      more complex regions in which spared and affected pathways are crossing to detect
      very early alterations of the white matter that could not be detected in regions
      consisting of one fibre population only. Finally, the methods used in this study
      may have general applicability for other degenerative disorders and, beyond the
      clinical sphere, they could contribute to a better quantification and
      understanding of subtle effects generated by normal processes such as
      visuospatial attention or motor learning.

PMID- 21182972
TI  - Contribution of a government target to controlling Clostridium difficile in the
      NHS in England.
AB  - The introduction of mandatory surveillance of Clostridium difficile infection
      (CDI) in 2004 showed the scale of the challenge: cases in patients >64 years old
      reached 55,681 in 2006. The first type 027 outbreaks had been in 2005 and CDI was
      a headline issue. The prevention and control of CDI requires a tripartite
      partnership between clinicians, health service managers, and the
      government/Department of Health which needs to set standards, ensure that CDI is
      a priority, set targets and monitor outcome. Government can also legislate; the
      Health Act 2006 introduced a statutory Code of Practice for infection prevention
      and control for the NHS and extended to all independent health and care settings
      in 2010. In 2008, a national target was set for a 30% reduction in CDI by 2010-11
      (baseline 2007-8). It was population-based and set a standard (ceiling)
      rate/10,000 in each area, within which acute hospitals had a target/1000
      admissions (diagnosed after day 3). In the first year (2008-9), a 35% reduction
      was achieved from 55,499 to 36,079 cases in all ages and in 2009-10 the total was
      25,604, a 54% reduction from 2007-8. However, in 2009, cases >64 years old were
      29% down from 2008 but only 9% down in the 2-64 year old group; also, by this
      stage, cases in acute hospitals and in other settings were almost equal. Death
      certification showing CDI fell for the first time in 2008 and in 2009 there were
      3550 total mentions (7816 in 2007) of which 1510 (42%) were as underlying cause
      (3875, 49%, in 2007). The reductions in CDI have been achieved by a raft of
      measures. Crucially, the targets focused management emphasis on infection
      prevention and control. This was supported by enhanced surveillance. Clinical
      practice protocols were implemented through the high impact interventions (care
      bundle) approach, and there was a major emphasis on cleanliness and hygiene
      (particularly hand washing for clinical staff and environmental cleaning and
      disinfection in patient areas). Achievement of the target is not the end of the
      road; it is to be transformed into an objective (benchmark) for 2011 and beyond
      based on median rates to maintain pressure for reduction.

PMID- 21182971
TI  - Network discovery with DCM.
AB  - This paper is about inferring or discovering the functional architecture of
      distributed systems using Dynamic Causal Modelling (DCM). We describe a scheme
      that recovers the (dynamic) Bayesian dependency graph (connections in a network)
      using observed network activity. This network discovery uses Bayesian model
      selection to identify the sparsity structure (absence of edges or connections) in
      a graph that best explains observed time-series. The implicit adjacency matrix
      specifies the form of the network (e.g., cyclic or acyclic) and its graph
      theoretical attributes (e.g., degree distribution). The scheme is illustrated
      using functional magnetic resonance imaging (fMRI) time series to discover
      functional brain networks. Crucially, it can be applied to experimentally evoked
      responses (activation studies) or endogenous activity in task-free (resting
      state) fMRI studies. Unlike conventional approaches to network discovery, DCM
      permits the analysis of directed and cyclic graphs. Furthermore, it eschews
      (implausible) Markovian assumptions about the serial independence of random
      fluctuations. The scheme furnishes a network description of distributed activity
      in the brain that is optimal in the sense of having the greatest conditional
      probability, relative to other networks. The networks are characterised in terms
      of their connectivity or adjacency matrices and conditional distributions over
      the directed (and reciprocal) effective connectivity between connected nodes or
      regions. We envisage that this approach will provide a useful complement to
      current analyses of functional connectivity for both activation and resting-state
      studies.

PMID- 21182973
TI  - Guidance for developing phase II cell therapy trial proposals for consideration
      by the Blood and Marrow Transplant Clinical Trials Network.

PMID- 21182974
TI  - Retrospective outcome data for hematopoietic stem cell transplantation in
      patients with concurrent coronary artery disease.
AB  - Hematopoietic stem cell transplantation (HSCT) represents an extended period of
      physiologic stress. It is unknown whether patients with pre-existing coronary
      artery disease (CAD) may be poor transplant candidates. There are no data
      analyzing the risk of transplantation in this population. Sixty-nine patients
      with CAD who underwent 72 transplantations, autologous and allogeneic, were
      identified retrospectively. Fifty-five percent of these patients had prior
      percutaneous coronary intervention, 42% had verifiable history of myocardial
      infarction, and 23% had prior coronary artery bypass grafting. Outcomes were
      compared to 1109 patients without established CAD who underwent 1183 transplants
      during the same time period. Cancer diagnoses in the 2 groups were similar,
      predominantly lymphoma, multiple myeloma, and leukemia. There was no significant
      difference between the CAD group and the control group with respect to type of
      transplant (autologous 68% versus 64%, P = .612, myeloablative 86% versus 85%, P
      = .867). Treatment-related mortality was no different in the CAD group versus the
      control group (5.6% versus 4.9%, P = .777), nor were there differences in
      mortality at 1 year (15.3% versus 16.6%, P = .871), urgent intensive care unit
      admission (11.1% versus 9.9%, P = .686), or length of stay (25.5 days versus 28.4
      days, P = .195). These findings suggest many patients with underlying coronary
      artery disease may be safely managed through hematopoietic stem cell
      transplantation.

PMID- 21182976
TI  - Nitric oxide changes distinct aspects of the glycophenotype of human
      neuroblastoma NB69 cells.
AB  - It is an open question whether the presence of nitric oxide (NO) affects the cell
      glycophenotype. A panel of six plant lectins was used in this study to monitor
      distinct aspects of cell surface glycosylation under nitrosative stress. We
      determined that treating human neuroblastoma NB69 cells with the long-lived NO
      donor 2,2'-(hydroxynitrosohydrazono)bis-ethanimine (DETA/NO) and monitoring the
      non-apoptotic adherent cell population significantly increases the presentation
      of N-glycans as detected by concanavalin A. Examining fine-structural features,
      bisected N-glycans and branch-end tailoring including alpha2,6-sialylation were
      found to be enhanced. Confocal fluorescence microscopy and cell permeabilization
      experiments pointed to a major effect of NO on the extent of cell surface N
      glycan presentation. We also show that NO increases the level of protein O
      GlcNAcylation, a multifunctional post-translational modification. Our results
      thus establish the first evidence for NO as modulator of distinct aspects of cell
      glycosylation.

PMID- 21182975
TI  - Allogeneic hematopoietic cell transplantation with full-intensity conditioning
      for adult acute lymphoblastic leukemia: results from a single center, 1998-2006.
AB  - A retrospective analysis identified 161 consecutive adults with acute
      lymphoblastic leukemia who underwent allogeneic hematopoietic cell
      transplantation (HCT) with full-intensity (myeloablative) conditioning between
      1998 and 2006. Median patient age was 36.1 years. Seventy-six patients were in
      first complete remission (CR1), and 85 were in second or greater CR or in
      relapse. Fifty-nine patients had Philadelphia chromosome-positive acute
      lymphoblastic leukemia. A total of 159 patients received chemotherapy plus total
      body irradiation for conditioning. Graft-versus-host disease prophylaxis included
      a calcineurin inhibitor plus methotrexate or mycophenolate mofetil. Sixty of the
      donors were related, and 101 were unrelated. A total of 110 patients received
      granulocyte-colony stimulating factor-stimulated peripheral blood, 47 received
      bone marrow, and 4 received cord blood as the stem cell source. Fifty-five
      patients relapsed at a median of 231 days after transplantation. The estimated 5
      year probabilities of relapse-free survival, relapse, and nonrelapse mortality
      were 47%, 30%, and 29%, respectively. By multivariate analyses, transplantation
      while in CR1 was the most important predictor of successful transplantation.
      Pretransplantation evidence of minimal residual disease, especially as detected
      by flow cytometric analysis, was associated with both lower overall survival and
      lower relapse-free survival. Compared with a similar cohort of patients
      undergoing transplantation between 1990 and 1997, overall survival was similar
      for patients undergoing transplantation in CR1, with lower nonrelapse mortality
      being offset by higher rates of relapse in patients who underwent transplantation
      more recently.

PMID- 21182977
TI  - What can in vitro models of COPD tell us?
AB  - Chronic obstructive pulmonary disease (COPD) is a progressive lung disease
      characterised by chronic bronchitis, largely irreversible remodelling of the
      small airways, and emphysematous destruction of the alveoli. COPD is projected to
      be the third leading cause of death worldwide by 2020. COPD often results from
      prolonged exposure to irritants such as cigarette smoke or inhaled particulates.
      Current pharmacotherapies for COPD are unable to reverse the pathological changes
      of this disease, and this is partially due to a limited understanding of the
      intricate mechanisms by which chronic exposure lead to the different pathological
      components of COPD. This review examines how the mechanisms that underlie various
      components of COPD can be modelled in vitro, specifically using cigarette smoke
      extract with cells cultured from primary human lung tissue, and how the
      effectiveness of current and novel pharmacotherapies on successfully attenuating
      these pathological changes can also be examined in vitro.

PMID- 21182978
TI  - Uric acid deposits and estivation in the invasive apple-snail, Pomacea
      canaliculata.
AB  - The physiological ability to estivate is relevant for the maintenance of
      population size in the invasive Pomacea canaliculata. However, tissue
      reoxygenation during arousal from estivation poses the problem of acute oxidative
      stress. Uric acid is a potent antioxidant in several systems and it is stored in
      specialized tissues of P. canaliculata. Changes in tissue concentration of
      thiobarbituric acid reactive substances (TBARS), uric acid and allantoin were
      measured during estivation and arousal in P. canaliculata. Both TBARS and uric
      acid increased two-fold during 45 days estivation, probably as a consequence of
      concomitant oxyradical production during uric acid synthesis by xanthine oxidase.
      However, after arousal was induced, uric acid and TBARS dropped to or near
      baseline levels within 20 min and remained low up to 24h after arousal induction,
      while the urate oxidation product allantoin continuously rose to a maximum at 24h
      after induction, indicating the participation of uric acid as an antioxidant
      during reoxygenation. Neither uric acid nor allantoin was detected in the excreta
      during this 24h period. Urate oxidase activity was also found in organs of active
      snails, but activity shut down during estivation and only a partial and sustained
      recovery was observed in the midgut gland.

PMID- 21182980
TI  - The role of Fras1/Frem proteins in the structure and function of basement
      membrane.
AB  - Basement membranes constitute architecturally complex extracellular matrix (ECM)
      protein networks of great structural and regulatory importance. Recently, a novel
      group of basement membrane proteins, Fras1 (Fraser syndrome protein (1) and the
      Fras1-related extracellular matrix proteins Frem1, Frem2 and Frem3, has emerged.
      They comprise components of the sublamina densa region and contribute to
      embryonic epithelial-mesenchymal integrity. Fras1/Frem share common polypeptide
      repetitive motifs with possible interactive and organizing functions. Mutations
      in genes encoding Fras1, Frem1 and Frem2 are causative for dermal-epidermal
      detachment in the plane of sublamina densa and have been identified in different
      classes of mouse bleb mutants, the murine model of human Fraser syndrome, the
      hallmark phenotypic characteristics of which are embryonic skin blistering,
      cryptophthalmos and renal agenesis. Indeed, defects in FRAS1 and FREM2 have been
      identified in Fraser syndrome patients. The phenotypic similarity of mouse bleb
      mutant strains can be attributed to the fact that Fras1, Frem1 and Frem2 have
      been experimentally shown to interact, forming a mutually stabilized protein
      complex, while Frem3, which has not yet been associated with any of the existing
      known mutations, operates in a more independent fashion. Fras1/Frem have been
      recently proposed to compensate for the activity of collagen VII, a major
      anchoring component of the sublamina densa, the levels of which rise only during
      late embryonic life. By focusing on the aforementioned data, in this review we
      will summarize the current knowledge about Fraser syndrome proteins and describe
      their contribution to basement membrane biology.

PMID- 21182979
TI  - Morphological plasticity promotes resistance to phagocyte killing of
      uropathogenic Escherichia coli.
AB  - Uropathogenic Escherichia coli proceed through a complex intracellular
      developmental pathway that includes multiple morphological changes. During
      intracellular growth within Toll-like receptor 4-activated superficial bladder
      epithelial cells, a subpopulation of uropathogenic E. coli initiates SulA
      mediated filamentation. In this study, we directly investigated the role of
      bacterial morphology in the survival of uropathogenic E. coli from killing by
      phagocytes. We initially determined that both polymorphonuclear neutrophils and
      macrophages are recruited to murine bladder epithelium at times coincident with
      extracellular bacillary and filamentous uropathogenic E. coli. We further
      determined that bacillary uropathogenic E. coli were preferentially destroyed
      when mixed uropathogenic E. coli populations were challenged with cultured murine
      macrophages in vitro. Consistent with studies using elliptical-shaped polymers,
      the initial point of contact between the phagocyte and filamentous uropathogenic
      E. coli influenced the efficacy of internalization. These findings demonstrate
      that filamentous morphology provides a selective advantage for uropathogenic E.
      coli evasion of killing by phagocytes and defines a mechanism for the essential
      role for SulA during bacterial cystitis. Thus, morphological plasticity can be
      viewed as a distinct class of mechanism used by bacterial pathogens to subvert
      host immunity.

PMID- 21182981
TI  - Newly developed strategies for multifunctional mitochondria-targeted agents in
      cancer therapy.
AB  - The development of multifunctional agents that could be used for simultaneous
      tumor targeting, imaging and treatment is a major goal in cancer research and is
      expected to contribute significantly to the realization of personalized oncology.
      Mitochondria are involved in diverse physiological activities and confer vital
      roles in cancer development and progression. Increasing efforts are being made to
      develop cancer treatment strategies based on various mitochondrial targets and
      novel mitochondrial drug delivery systems. Multifunctional nanostructures or
      multifunctional chemical compounds further broaden the current concept of tumor
      targeting and provide alternative solutions for mitochondrially targeted cancer
      therapy.

PMID- 21182982
TI  - Improvement of in vivo genotoxicity assessment: combination of acute tests and
      integration into standard toxicity testing.
AB  - A working group convened at the 2009 5th IWGT to discuss possibilities for
      improving in vivo genotoxicity assessment by investigating possible links to
      standard toxicity testing. The working group considered: (1) combination of acute
      micronucleus (MN) and Comet assays into a single study, (2) integration of MN
      assays into repeated-dose toxicity (RDT) studies, (3) integration of Comet assays
      into RDT studies, and (4) requirements for the top dose when integrating
      genotoxicity measurements into RDT studies. The working group reviewed current
      requirements for in vivo genotoxicity testing of different chemical product
      classes and identified opportunities for combination and integration of
      genotoxicity endpoints for each class. The combination of the acute in vivo MN
      and Comet assays was considered by the working group to represent a technically
      feasible and scientifically acceptable alternative to conducting independent
      assays. Two combination protocols, consisting of either a 3- or a 4-treament
      protocol, were considered equally acceptable. As the integration of MN assays
      into RDT studies had already been discussed in detail in previous IWGT meetings,
      the working group focussed on factors that could affect the results of the
      integrated MN assay, such as the possible effects of repeated bleeding and the
      need for early harvests. The working group reached the consensus that repeated
      bleeding at reasonable volumes is not a critical confounding factor for the MN
      assay in rats older than 9 weeks of age and that rats bled for toxicokinetic
      investigations or for other routine toxicological purposes can be used for MN
      analysis. The working group considered the available data as insufficient to
      conclude that there is a need for an early sampling point for MN analysis in RDT
      studies, in addition to the routine determination at terminal sacrifice. Specific
      scenarios were identified where an additional early sampling can have advantages,
      e.g., for compounds that exert toxic effects on hematopoiesis, including some
      aneugens. For the integration of Comet assays into RDT studies, the working group
      reached the consensus that, based upon the limited amount of data available,
      integration is scientifically acceptable and that the liver Comet assay can
      complement the MN assay in blood or bone marrow in detecting in vivo genotoxins.
      Practical issues need to be considered when conducting an integrated Comet assay
      study. Freezing of tissue samples for later Comet assay analysis could alleviate
      logistical problems. However, the working group concluded that freezing of tissue
      samples can presently not be recommended for routine use, although it was noted
      that results from some laboratories look promising. Another discussion topic
      centred around the question as to whether tissue toxicity, which is more likely
      observed in RDT than in acute toxicity studies, would affect the results of the
      Comet assay. Based on the available data from in vivo studies, the working group
      concluded that there are no clear examples where cytotoxicity, by itself,
      generates increases or decreases in DNA migration. The working group identified
      the need for a refined guidance on the use and interpretation of cytotoxicity
      methods used in the Comet assay, as the different methods used generally lead to
      inconsistent conclusions. Since top doses in RDT studies often are limited by
      toxicity that occurs only after several doses, the working group discussed
      whether the sensitivity of integrated genotoxicity studies is reduced under these
      circumstances. For compounds for which in vitro genotoxicity studies yielded
      negative results, the working group reached the consensus that integration of in
      vivo genotoxicity endpoints (typically the MN assay) into RDT studies is
      generally acceptable. If in vitro genotoxicity results are unavailable or
      positive, consensus was reached that the maximum tolerated dose (MTD) is
      acceptable as the top dose in RDT studies in many cases, such as when the RDT
      study MTD or exposure is close (50% or greater) to an acute study MTD or
      exposure. Finally, the group agreed that exceptions to this general rule might be
      acceptable, for example when human exposure is lower than the preclinical
      exposure by a large margin.

PMID- 21182983
TI  - Practical applications of structural genomics technologies for mutagen research.
AB  - Here we present a perspective on a range of practical uses of structural genomics
      for mutagen research. Structural genomics is an overloaded term and requires some
      definition to bound the discussion; we give a brief description of public and
      private structural genomics endeavors, along with some of their objectives, their
      activities, their capabilities, and their limitations. We discuss how structural
      genomics might impact mutagen research in three different scenarios: at a
      structural genomics center, at a lab with modest resources that also conducts
      structural biology research, and at a lab that is conducting mutagen research
      without in-house experimental structural biology. Applications span functional
      annotation of single genes or SNP, to constructing gene networks and pathways, to
      an integrated systems biology approach. Structural genomics centers can take
      advantage of systems biology models to target high value targets for structure
      determination and in turn extend systems models to better understand systems
      biology diseases or phenomenon. Individual investigator run structural biology
      laboratories can collaborate with structural genomics centers, but can also take
      advantage of technical advances and tools developed by structural genomics
      centers and can employ a structural genomics approach to advancing biological
      understanding. Individual investigator-run non-structural biology laboratories
      can also collaborate with structural genomics centers, possibly influencing
      targeting decisions, but can also use structure based annotation tools enabled by
      the growing coverage of protein fold space provided by structural genomics.
      Better functional annotation can inform pathway and systems biology models.

PMID- 21182984
TI  - Response to jejunal cancer in patients with familial adenomatous polyposis.

PMID- 21182985
TI  - 2011 ACCF/AHA/HRS focused update on the management of patients with atrial
      fibrillation (Updating the 2006 Guideline): a report of the American College of
      Cardiology Foundation/American Heart Association Task Force on Practice
      Guidelines.

PMID- 21182986
TI  - Low genetic polymorphism of merozoite surface proteins 7 and 10 in Colombian
      Plasmodium vivax isolates.
AB  - The merozoite surface protein (MSP) family is involved in the initial interaction
      between merozoites and erythrocytes in Plasmodium species, its members are
      therefore becoming major targets for vaccine development. Considering that
      antigens included in a subunit malaria vaccine should be both accessible to the
      immune system and lack genetic diversity or have very limited polymorphism, we
      have analyzed the genetic diversity of three msp genes (msp-7A, msp-7K and msp
      10) in different geographical regions of Colombia. The results showed that these
      genes follow the neutral model of evolution and also display low genetic
      diversity. The strong conservation found for msp-7 haplotypes in isolates from
      geographically different regions further suggests that these proteins could be
      good components of a vaccine against Plasmodium vivax malaria, thereby avoiding
      strain-specific immune responses.

PMID- 21182987
TI  - Vaccination in adult patients with auto-immune inflammatory rheumatic diseases: a
      systematic literature review for the European League Against Rheumatism evidence
      based recommendations for vaccination in adult patients with auto-immune
      inflammatory rheumatic diseases.
AB  - OBJECTIVES: To present the systematic literature review (SLR), which formed the
      basis for the European League Against Rheumatism (EULAR) evidence-based
      recommendations for vaccination in adult patients with auto-immune inflammatory
      rheumatic diseases (AIIRD). METHODS: AIIRD, vaccines and immunomodulating drugs,
      as well as eight key questions were defined by the multidisciplinary expert
      committee commissioned by EULAR for developing the recommendations. A SLR was
      performed using MedLine through October 2009 and including data from meta
      analyses, systematic reviews, randomized trials, and observational studies,
      excluding case series with <= 5 participants. Articles in English and regarding
      patients >= 16 years of age, were eligible. RESULTS: Several vaccine-preventable
      infections (VPI) occur more often in AIIRD-patients and most vaccines are
      efficacious in AIIRD-patients, even when treated with immunomodulating agents,
      except rituximab. There does not appear to be an increase in vaccination-related
      harms in vaccinated patients with AIIRD in comparison with unvaccinated patients
      with AIIRD. However, these studies are underpowered and therefore not conclusive.
      CONCLUSION: Based on the current evidence from the literature, recommendations
      for vaccination in patients with AIIRD were made. However, more research is
      needed in particular regarding incidence of VPI, harms of vaccination and the
      influence of (new and established) immunomodulating agents on vaccination
      efficacy.

PMID- 21182988
TI  - Alternating ventilation in a rat model of increased abdominal pressure.
AB  - During alternating ventilation (AV) one lung is inflating while the other is
      deflating. Considering the possible respiratory and hemodynamic advantages of AV,
      we investigated its effects during increased intra-abdominal pressure (IAP=10
      mmHg). In Sprague-Dawley rats (n=6, 270-375g) the main bronchi were independently
      cannulated, and respiratory mechanics determined while animals underwent
      different ventilatory patterns: synchronic ventilation without increased IAP (SV
      0), elevated IAP during SV (SV-10), and AV with elevated IAP (AV-10). Thirty
      three other animals (SV-0, n=10; SV-10, n=11 and AV-10, n=12) were ventilated
      during 3h. Mean arterial pressure (MAP), and lung histology were assessed.
      Increased IAP resulted in significantly higher elastances (p<0.001), being AV-10
      lower than SV-10 (p<0.020). SV-10 showed higher central venous pressure (p<0.003)
      than S-0; no change was observed in AV-10. Wet/dry lung weight ratio was lower in
      AV-10 than SV-10 (p=0.009). Application of AV reduced hemodynamic and lung
      impairments induced by increased IAP during SV.

PMID- 21182989
TI  - Vitamin B(6) salvage enzymes: mechanism, structure and regulation.
AB  - Vitamin B(6) is a generic term referring to pyridoxine, pyridoxamine, pyridoxal
      and their related phosphorylated forms. Pyridoxal 5'-phosphate is the
      catalytically active form of vitamin B(6), and acts as cofactor in more than 140
      different enzyme reactions. In animals, pyridoxal 5'-phosphate is recycled from
      food and from degraded B(6)-enzymes in a "salvage pathway", which essentially
      involves two ubiquitous enzymes: an ATP-dependent pyridoxal kinase and an FMN
      dependent pyridoxine 5'-phosphate oxidase. Once it is made, pyridoxal 5'
      phosphate is targeted to the dozens of different apo-B(6) enzymes that are being
      synthesized in the cell. The mechanism and regulation of the salvage pathway and
      the mechanism of addition of pyridoxal 5'-phosphate to the apo-B(6)-enzymes are
      poorly understood and represent a very challenging research field. Pyridoxal
      kinase and pyridoxine 5'-phosphate oxidase play kinetic roles in regulating the
      level of pyridoxal 5'-phosphate formation. Deficiency of pyridoxal 5'-phosphate
      due to inborn defects of these enzymes seems to be involved in several
      neurological pathologies. In addition, inhibition of pyridoxal kinase activity by
      several pharmaceutical and natural compounds is known to lead to pyridoxal 5'
      phosphate deficiency. Understanding the exact role of vitamin B(6) in these
      pathologies requires a better knowledge on the metabolism and homeostasis of the
      vitamin. This article summarizes the current knowledge on structural, kinetic and
      regulation features of the two enzymes involved in the PLP salvage pathway. We
      also discuss the proposal that newly formed PLP may be transferred from either
      enzyme to apo-B(6)-enzymes by direct channeling, an efficient, exclusive, and
      protected means of delivery of the highly reactive PLP. This new perspective may
      lead to novel and interesting findings, as well as serve as a model system for
      the study of macromolecular channeling. This article is part of a Special Issue
      entitled: Pyridoxal Phosphate Enzymology.

PMID- 21182990
TI  - Pyridoxal-5'-phosphate-dependent enzymes involved in biotin biosynthesis:
      structure, reaction mechanism and inhibition.
AB  - The four last steps of biotin biosynthesis, starting from pimeloyl-CoA, are
      conserved among all the biotin-producing microorganisms. Two enzymes of this
      pathway, the 8-amino-7-oxononanoate synthase (AONS) and the 7,8-diaminopelargonic
      acid aminotransferase (DAPA AT) are dependent on pyridoxal-5'-phosphate (PLP).
      This review summarizes our current understanding of the structure, reaction
      mechanism and inhibition on these two interesting enzymes. Mechanistic studies as
      well as the determination of the crystal structure of AONS have revealed a
      complex mechanism involving an acylation with inversion of configuration and a
      decarboxylation with retention of configuration. This reaction mechanism is
      shared by the homologous 5-aminolevulinate synthase and serine
      palmitoyltransferase. While the reaction catalyzed by DAPA AT is a classical PLP
      dependent transamination, the inactivation of this enzyme by amiclenomycin, a
      natural antibiotic that is active against Mycobacterium tuberculosis, involves
      the irreversible formation of an adduct between PLP and amiclenomycin.
      Mechanistic and structural studies allowed the complete description of this
      unique inactivation mechanism. Several potent inhibitors of these two PLP
      dependent enzymes have been prepared and might be useful as starting points for
      the design of herbicides or antibiotics. This article is part of a Special Issue
      entitled: Pyridoxal Phospate Enzymology.

PMID- 21182991
TI  - The PLP cofactor: lessons from studies on model reactions.
AB  - Experimental probes of the acidity of weak carbon acids have been developed and
      used to determine the carbon acid pK(a)s of glycine, glycine derivatives and
      iminium ion adducts of glycine to the carbonyl group, including 5'-deoxypyridoxal
      (DPL). The high reactivity of the DPL-stabilized glycyl carbanion towards
      nucleophilic addition to both DPL and the glycine-DPL iminium ion favors the
      formation of Claisen condensation products at enzyme active sites. The formation
      of the iminium ion between glycine and DPL is accompanied by a 12-unit decrease
      in the pK(a) of 29 for glycine. The complicated effects of formation of glycine
      iminium ions to DPL and other aromatic and aliphatic aldehydes and ketones on
      carbon acid pK(a) are discussed. These data provide insight into the contribution
      of the individual pyridine ring substituents to the catalytic efficiency of DPL.
      It is suggested that the 5'-phosphodianion group of PLP may play an important
      role in enzymatic catalysis of carbon deprotonation by providing up to 12
      kcal/mol of binding energy that is utilized to stabilize the transition state for
      the enzymatic reaction. This article is part of a Special Issue entitled:
      Pyridoxal Phospate Enzymology.

PMID- 21182992
TI  - Normative data and percentile curves for Dual Energy X-ray Absorptiometry in
      healthy Indian girls and boys aged 5-17 years.
AB  - For the correct interpretation of Dual Energy X-ray Absorptiometry (DXA)
      measurements in children, the use of age, gender, height, weight and ethnicity
      specific reference data is crucially important. In the absence of such a database
      for Indian children, the present study aimed to provide gender and age specific
      data on bone parameters and reference percentile curves for the assessment of
      bone status in 5-17 year old Indian boys and girls. A cross sectional study was
      conducted from May 2006 to July 2010 on 920 (480 boys) apparently healthy
      children from schools and colleges in Pune City, India. The GE-Lunar DPX Pro
      Pencil Beam DXA scanner was used to measure bone mineral content (BMC [g]), bone
      area (BA [cm(2)]) and bone mineral density (BMD [g/cm(2)]) at total body, lumbar
      spine and left femur. Reference percentile curves by age were derived separately
      for boys and girls for the total body BMC (TBBMC), total body BA (TBBA), lumbar
      spine bone mineral apparent density (BMAD [g/cm(3)]), and left femoral neck BMAD.
      We have also presented percentile curves for TBBA for height, TBBMC for TBBA, LBM
      for height and TBBMC for LBM for normalizing bone data for Indian children. Mean
      TBBMC, TBBA and TBBMD were expressed by age groups and Tanner stages for boys and
      girls separately. The average increase in TBBMC and TBBA with age was of the
      order of 8 to 12% at each age group. After 16 years of age, TBBMC and TBBA were
      significantly higher in boys than in girls (p<0.01). Maximal increase in TBBMD
      occurred around the age of 13 years in girls and three years later in boys.
      Reference data provided may be used for the clinical assessment of bone status of
      Indian children and adolescents.

PMID- 21182993
TI  - Immunization with recombinant DNA and modified vaccinia virus Ankara (MVA)
      vectors delivering PSCA and STEAP1 antigens inhibits prostate cancer progression.
AB  - Despite recent advances in early detection and improvement of conventional
      therapies, there is an urgent need for development of additional approaches for
      prevention and/or treatment of prostate cancer, and the use of immunotherapeutic
      modalities, such as cancer vaccines, is one of the most promising strategies. In
      this study, we evaluated the prophylactic efficacy of an active immunization
      protocol against prostate cancer associated antigens mPSCA and mSTEAP1 in
      experimental prostate cancer. Two antigen delivery platforms, recombinant DNA and
      MVA vectors, both encoding either mPSCA or mSTEAP1 were used in diversified DNA
      prime/MVA boost vaccination protocol. Antitumour activity was evaluated in TRAMP
      C1 subcutaneous syngeneic tumour model and TRAMP mice. DNA prime/MVA boost
      immunization against either mPSCA or mSTEAP1, delayed tumour growth in TRAMP-C1
      cells-challenged mice. Furthermore, simultaneous vaccination with both antigens
      produced a stronger anti-tumour effect against TRAMP-C1 tumours than vaccination
      with either mPSCA or mSTEAP1 alone. Most importantly, concurrent DNA prime/MVA
      boost vaccination regimen with those antigens significantly decreased primary
      tumour burden in TRAMP mice without producing any apparent adverse effects.
      Histopathological analysis of prostate tumours from vaccinated and control TRAMP
      mice revealed also that mPSCA/mSTEAP1 based-vaccination was effective at reducing
      the severity of prostatic lesions and incidence of high-grade poorly
      differentiated prostate cancer. Suppression of the disease progression in TRAMP
      mice was correlated with decreased proliferation index and increased infiltration
      of T-cells in prostate tissue. Active immunization against PSCA and STEAP1 using
      DNA prime/MVA boost strategy is a promising approach for prevention and/or
      treatment of prostate cancer.

PMID- 21182994
TI  - Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae
      prior to introduction of the 10-valent pneumococcal conjugate vaccine in Brazil,
      2000-2007.
AB  - This study describes the serotype distribution and antibiotic resistance patterns
      among 397 S. pneumoniae meningitis case isolates recovered in Salvador, Brazil,
      during the period of 2000-2007, before introduction of the 10-valent pneumococcal
      conjugate vaccine. The active hospital-based surveillance showed a decline in the
      annual incidence rates of pneumococcal meningitis during the period of study,
      from 1.12 cases to 0.83 cases/100,000 persons for all age groups (P<0.001), with
      an overall case-fatality rate of 28.6% (113 of 395) for all patients and 41.9%
      (57 of 136) for those <5 years of age. Serotypes 14 (n=55; 13.9%), 3 (n=32;
      8.1%), 23F (n=32; 8.1%), 19F (n=31; 7.8%), 6B (n=30; 7.6%), 18C (n=28; 7.1%), and
      6A (n=20; 5%) were the most prevalent serotypes. In patients <5 years the
      estimated projected coverage of 7-, 10- and 13-valent conjugate vaccines was
      74.3%, 75.7% and 83.1%, respectively. Antimicrobial susceptibility testing
      revealed that 22.1% (n=88) of isolates were non-susceptible to penicillin, 56%
      were non-susceptible to trimethoprim/sulphamethoxazole, and 29.6% were non
      susceptible to tetracycline. Nonsusceptibility to penicillin and cefotaxime was
      detected solely among serotype 14 isolates (n=4; 1%). This study provides an
      important baseline to assess the impact of conjugate vaccine implantation on the
      epidemiology of meningitis due to Streptococcus pneumoniae in Salvador, Brazil.

PMID- 21182996
TI  - Coverage and predictors of vaccination against 2009 pandemic H1N1 influenza in
      Madrid, Spain.
AB  - This study aimed to ascertain the coverage of vaccination against pandemic
      influenza in individuals aged over 6 months for whom vaccination is indicated due
      to a chronic health condition using as data source clinical information recorded
      in the primary care clinical history. Of all those for whom vaccination was
      indicated (1,114,632), 14.6% (162,616) finally received the vaccine. There were
      statistically significance differences in coverage for sex (16.5% for men and
      13.1% for women), age groups (5% for people under 30 years and 20% for those over
      60), number of chronic conditions (11.1% for one condition, 22.5% for two
      conditions, and 31.3% for three or more conditions) and depending on the chronic
      health condition considered. The probability of being vaccinated increased with
      male sex, age, number of indications, type of medical card (lower among no
      income) and having been vaccinated against 2009 season influenza. We concluded
      that the coverage finally reached for those people with an indication due to
      chronic health condition in the H1N1 campaign was much lower than expected and
      wished. It is essential to investigate the different factors that could have
      intervened in the behavior of the population so that more efficient approaches
      can be adopted in future influenza pandemics.

PMID- 21182997
TI  - CpG oligodeoxynucleotide-adjuvanted fusion peptide derived from HBcAg epitope and
      HIV-Tat may elicit favorable immune response in PBMCs from patients with chronic
      HBV infection in the immunotolerant phase.
AB  - The absence or insufficiency of specific immune response results in chronic
      hepatitis B virus (HBV) infection and immunotolerance. Therapeutic fusion peptide
      containing hepatitis B core antigen (HBcAg)(18-27) CTL epitope and human
      immunodeficiency virus (HIV)-Tat(49-57) peptide was synthesized and the activity
      when adjuvanted with CpG oligodeoxynucleotide (CpG ODN) was evaluated in PBMCs
      from patients with chronic HBV infection in the immunotolerant phase in this
      study. Results showed that the fusion peptide when adjuvanted with CpG ODN could
      induce significantly higher levels of IFN-gamma and IL-4 in the PBMCs compared
      with fusion peptide or CpG ODN alone. The magnitude of augmentation to IFN-gamma
      by the fusion peptide plus CpG ODN was much higher than that to IL-4.
      Cytotoxicity assay showed that the percentage of target cell lysis by effector
      cells stimulated by fusion peptide plus CpG ODN was higher than that in fusion
      peptide or CpG ODN alone at most of the E/T ratios tested. The magnitude
      augmented to IFN-gamma by fusion peptide plus CpG ODN was also much higher than
      that to the percentage of target cell lysis. It is concluded that HBcAg(18-27)
      and HIV-Tat(49-57) fusion peptide when adjuvanted with CpG ODN may have much
      higher potency to induce IFN-gamma than to induce IL-4 and cytotoxicity,
      suggesting the favorable immune response towards noncytolytic inactivation of the
      virus mediated by IFN-gamma and the potential to break the tolerant state in
      chronic HBV infection.

PMID- 21183000
TI  - Football left atrium.

PMID- 21182995
TI  - Immunogenicity of attenuated measles virus engineered to express Helicobacter
      pylori neutrophil-activating protein.
AB  - Helicobacter pylori is a Gram-negative, spiral-shaped microorganism associated
      with acute and chronic gastritis, peptic ulcer, gastric cancer and gastric
      lymphomas in humans. H. pylori neutrophil-activating protein (NAP) is a major
      virulence factor playing a central role in pathogenesis of mucosal inflammation
      by immune cell attraction and Th1 cytokine response polarization. NAP is
      protective antigen and promising vaccine candidate against H. pylori infection.
      Here we present the development of measles virus (MV) vaccine strain encoding the
      NAP antigen. In order to facilitate the extracellular transport and detection,
      NAP was inserted in the human lambda immunoglobulin chain replacing a major part
      of the variable domain. We generated two MV vectors expressing secretory NAP
      forms: MV-lambda-NAP encoding the full-length constant lambda light chain domain
      and MV-s-NAP encoding only the N-terminus of the lambda light chain with the
      leader peptide. Immunization of MV permissive Ifnarko-CD46Ge transgenic mice by a
      single intraperitoneal injection of the NAP-expressing strains induced a robust,
      long-term humoral and cellular immune response against MV. Nine months post
      vaccination measles-neutralizing antibody titers were above the serum level
      considered protective for humans. Furthermore, all animals immunized with MV
      strains expressing the secretory NAP antigen developed strong humoral immunity
      against NAP, reaching titers >1:10,000 within 2-4 weeks. IFN-gamma ELISpot assay
      confirmed that NAP-encoding MV vectors can also stimulate NAP-specific cell
      mediated immunity. Our data demonstrate that MV is an excellent vector platform
      for expression of bacterial antigens and development of vaccines for H. pylori
      immunoprophylaxis in humans.

PMID- 21183002
TI  - Leadership in academic medicine.

PMID- 21183003
TI  - Education of quality and safety requires learning about clinical data.

PMID- 21183004
TI  - Improving Practices in US Hospitals to Prevent Venous Thromboembolism: lessons
      from ENDORSE.
AB  - BACKGROUND: venous thromboembolism prophylaxis is suboptimal in the US despite
      long-standing evidence-based recommendations. The aim of this subset analysis of
      the Epidemiologic International Day for the Evaluation of Patients at Risk for
      Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE) study was to
      identify characteristics of hospitals with high guideline-recommended prophylaxis
      use. METHODS: between September and November 2006, charts from eligible patients
      aged >= 40 years with an acute medical illness or age >= 18 years and undergoing
      a surgical procedure were reviewed from randomly selected US acute-care
      hospitals. Hospitals were ranked based on the proportion of at-risk patients who
      received American College of Chest Physicians-recommended types of prophylaxis.
      Hospital characteristics were compared to determine factors related to more
      frequent prophylaxis use. Hospitals were followed up 1 year after the chart
      audit. RESULTS: overall, 9257 patients were evaluated from 81 hospitals.
      Appropriate types of prophylaxis were prescribed to more at-risk patients in
      hospitals in the highest quartile compared with the lowest quartile of
      prophylaxis use (74% vs 36%). All quartiles had a similar percentage of at-risk
      patients (61%-65%). Significantly more hospitals in the highest quartile had
      residency training programs (43% vs 5%), a larger median number of beds (277 vs
      140), and had adopted hospital-wide prophylaxis protocols (76% vs 40%). In the
      follow-up survey, more hospitals overall had adopted hospital-wide written
      guidelines for venous thromboembolism prevention. CONCLUSIONS: these findings
      support the value of hospital-wide protocols and local audits for VTE prevention,
      as recommended by several national quality-of-care groups.

PMID- 21183005
TI  - Increasing vancomycin serum trough concentrations and incidence of
      nephrotoxicity.
AB  - BACKGROUND: conflicting evidence regarding the association of vancomycin serum
      concentrations with efficacy and toxicity has resulted in controversy regarding
      optimal target concentrations. Recent publications recommend attaining higher
      vancomycin trough concentrations of 15 to 20 mg/L for target infections, yet
      limited research is available assessing the correlation of vancomycin serum
      concentrations with toxicity. The aim of this study was to evaluate the
      association between vancomycin serum trough concentrations and nephrotoxicity.
      METHODS: a 2-phase retrospective analysis was completed. Phase 1 evaluated 2493
      courses of vancomycin completed between January 2003 and December 2007. The
      analysis describes a 5-year trend in vancomycin prescribing practices and
      assesses the association of nephrotoxicity with baseline serum creatinine,
      vancomycin serum trough concentrations, and duration of vancomycin therapy. Phase
      2 examined patients receiving vancomycin therapy during 2007 to evaluate specific
      risk factors for development of nephrotoxicity. RESULTS: the proportion of
      vancomycin serum trough concentrations >= 15 mg/L and >= 20 mg/L increased
      significantly over time. Statistical analysis identified vancomycin serum trough
      concentrations >= 14 mg/L, duration of vancomycin therapy >= 7 days, and baseline
      serum creatinine levels >= 1.7 mg/dL as independent predictors of nephrotoxicity.
      Phase 2 analysis again implicated mean vancomycin serum trough concentration as a
      significant predictor of nephrotoxicity. Nephrotoxicity resolved in 81% (17/21)
      of cases evaluated. CONCLUSIONS: a higher vancomycin serum trough concentration
      and prolonged vancomycin therapy are associated with an increased risk of
      nephrotoxicity. The decision to target increased vancomycin trough concentrations
      should be based on an assessment of the severity of the infection and must
      consider the nephrotoxicity risk associated with increased vancomycin levels.

PMID- 21183006
TI  - Malignancy in systemic lupus erythematosus: a nationwide cohort study in Taiwan.
AB  - BACKGROUND: an increased risk of malignancy in patients with systemic lupus
      erythematosus has been reported, but rarely in Asian populations. We aimed to
      investigate the relative risk of cancer and to identify the high-risk group for
      cancer in patients with lupus. METHODS: we conducted a retrospective, nationwide
      cohort study that included 11,763 patients with lupus without a history of
      malignancies, using the national health insurance database of Taiwan from 1996 to
      2007. Standardized incidence ratios (SIRs) of cancers were analyzed. RESULTS: a
      total of 259 cancers were observed in patients with lupus. An elevated risk of
      cancer among those with systemic lupus erythematosus was noted (SIR 1.76; 95%
      confidence interval [CI] 1.74-1.79), especially for hematologic malignancies (SIR
      4.96; 95% CI 4.79-5.14). Younger patients had a greater risk ratio of cancer than
      the general population, and the risk ratio decreased with age. The risk ratio of
      cancer decreased with time, yet remained elevated compared with that of the
      general population. The risk of non-Hodgkin lymphoma was greatest (SIR 7.27)
      among hematologic cancers. Among solid tumors, the risk was greatest for cancers
      of the vagina/vulva (SIR 4.76), nasopharynx (SIR 4.18), and kidney (SIR 3.99). An
      elevated risk for less common cancers, including those of the brain, oropharynx,
      and thyroid glands, was also observed. CONCLUSION: patients with lupus are at
      increased risk of cancers and should receive age- and gender-appropriate
      malignancy evaluations, with additional assessment for vulva/vagina, kidney,
      nasopharynx, and hematologic malignancy. Continued vigilance for development of
      cancers in follow-up is recommended.

PMID- 21183007
TI  - AAIM report on master teachers and clinician educators, Part 5: Academic
      documentation and tenure.

PMID- 21183008
TI  - Using our brains: the findings, flaws, and future of postmortem studies of
      psychiatric disorders.

PMID- 21183009
TI  - Genetic neuropathology of schizophrenia: new approaches to an old question and
      new uses for postmortem human brains.
AB  - Human postmortem brain studies are critical for elucidating the pathophysiology
      and etiology of schizophrenia and other major mental illnesses. The traditional
      approach compares patients and control subjects but is potentially confounded by
      a number of artifacts, including medication, substance misuse, and other
      secondary effects of illness. Genetic advances now make possible a novel approach
      that focuses on how allelic variation in risk-associated genes affects expression
      and function of transcripts and proteins. These questions can be addressed in
      normal brain, overcoming to some extent the confounding effects of studying
      brains from subjects with schizophrenia; equally, extension of the studies to
      include cases also has advantages. Conceptually, the approach may be seen as the
      neuropathologic counterpart of genetic neuroimaging, representing a potentially
      powerful intermediate phenotype. For several schizophrenia susceptibility genes,
      the data show that risk-associated polymorphisms do affect gene expression or the
      function of the encoded protein; in some instances, expression of downstream or
      interacting partners of the gene are also altered. A further striking finding is
      that the implicated transcripts often appear to be enriched in, or specific to,
      human brain. Some also show enhanced expression in fetal brain. These
      considerations give unique importance to postmortem human brain tissue in
      elucidating the genetic mechanisms underlying schizophrenia and probably other
      neurodevelopmental disorders as well. Studies of this kind can provide clues as
      to the biological mechanisms of genetic association, especially when carried out
      in conjunction with experimental studies. Moreover, the data, interpreted
      judiciously, can strengthen the plausibility of the association itself.

PMID- 21183011
TI  - Toward the integration of expert knowledge and instrumental data to control food
      processes: application to Camembert-type cheese ripening.
AB  - Modeling the cheese ripening process remains a challenge because of its
      complexity. We still lack the knowledge necessary to understand the interactions
      that take place at different levels of scale during the process. However,
      information may be gathered from expert knowledge. Combining this expertise with
      knowledge extracted from experimental databases may allow a better understanding
      of the entire ripening process. The aim of this study was to elicit expert
      knowledge and to check its validity to assess the evolution of organoleptic
      quality during a dynamic food process: Camembert cheese ripening. Experiments on
      a pilot scale were carried out at different temperatures and relative humidities
      to obtain contrasting ripening kinetics. During these experiments, macroscopic
      evolution was evaluated from an expert's point of view and instrumental
      measurements were carried out to simultaneously monitor microbiological,
      physicochemical, and biochemical kinetics. A correlation of 76% was established
      between the microbiological, physicochemical, and biochemical data and the
      sensory phases measured according to expert knowledge, highlighting the validity
      of the experts' measurements. In the future, it is hoped that this expert
      knowledge may be integrated into food process models to build better decision-aid
      systems that will make it possible to preserve organoleptic qualities by linking
      them to other phenomena at the microscopic level.

PMID- 21183010
TI  - Altered microRNA expression profiles in postmortem brain samples from individuals
      with schizophrenia and bipolar disorder.
AB  - BACKGROUND: MicroRNAs (miRNAs) are potent regulators of gene expression with
      proposed roles in brain development and function. We hypothesized that miRNA
      expression profiles are altered in individuals with severe psychiatric disorders.
      METHODS: With real-time quantitative polymerase chain reaction, we compared the
      expression of 435 miRNAs and 18 small nucleolar RNAs in postmortem brain tissue
      samples from individuals with schizophrenia, individuals with bipolar disorder,
      and psychiatrically healthy control subjects (n = 35 each group). Detailed
      demographic data, sample selection and storage conditions, and drug and substance
      exposure histories were available for all subjects. Bayesian model averaging was
      used to simultaneously assess the impact of these covariates as well as the
      psychiatric phenotype on miRNA expression profiles. RESULTS: Of the variables
      considered, sample storage time, brain pH, alcohol at time of death, and
      postmortem interval were found to affect the greatest proportion of miRNAs. Of
      miRNAs analyzed, 19% exhibited positive evidence of altered expression due to a
      diagnosis of schizophrenia or bipolar disorder. Both conditions were associated
      with reduced miRNA expression levels, with a much more pronounced effect observed
      for bipolar disorder. CONCLUSIONS: This study suggests that modest
      underexpression of several miRNAs might be involved in the complex pathogenesis
      of major psychosis.

PMID- 21183012
TI  - Characterization of high-milk-protein powders upon rehydration under various salt
      concentrations.
AB  - Rehydration of native micellar casein and native whey isolate protein powders was
      followed in different ionic environments. Solutions of NaCl and CaCl2 in the
      concentration range of 0 to 12% (wt%) were used as rehydration media. The
      rehydration profiles obtained were interpreted in terms of wetting, swelling, and
      dispersion stages by using a turbidity method. Two behaviors were observed
      depending on the salt concentration. For native micellar casein powder, a
      significant change was observed between 3 and 6% NaCl and between 0.75 and 1.5%
      CaCl2. The first behavior (low salt concentration) presents a typical rehydration
      profile: quick wetting, swelling, and long dispersion stage. The dispersion stage
      of the second behavior (high salt concentration) was significantly shortened,
      indicating a strong modification of the protein backbone. The rehydration of whey
      protein powder was less influenced by salts. At low salt concentrations, a
      typical profile for whey powders was observed: wetting with lump formation and no
      swelling followed by a quick dispersion. At high CaCl2 concentrations, no
      turbidity stabilization was observed, indicating a possible protein unfolding and
      denaturation. Additionally, the changes in secondary structures of the 2 proteins
      upon salt increase were followed by Fourier transform infrared spectroscopy and
      confirmed the different profiles observed.

PMID- 21183013
TI  - Fat composition of organic and conventional retail milk in northeast England.
AB  - This study of UK retail milk identified highly significant variations in fat
      composition. The survey, conducted over 2 yr replicating summer and winter,
      sampled 22 brands, 10 of which indicated organic production systems. Results
      corroborate earlier farm-based findings considering fat composition of milk
      produced under conventional and organic management. Organic milk had higher
      concentrations of beneficial fatty acids (FA) than conventional milk, including
      total polyunsaturated fatty acids (PUFA; 39.4 vs. 31.8 g/kg of total FA),
      conjugated linoleic acid cis-9,trans-11 (CLA9; 7.4 v 5.6 g/kg of FA), and alpha
      linolenic acid (alpha-LN; 6.9 vs. 4.4 g/kg of FA). As expected, purchase season
      had a strong effect on fat composition: compared with milk purchased in winter,
      summer milk had a lower concentration of saturated fatty acids (682 vs. 725 g/kg
      of FA) and higher concentrations of PUFA (37.6 vs. 32.8 g/kg of FA), CLA9 (8.1
      vs. 4.7 g/kg of FA), and alpha-LN (6.5 vs. 4.6 g/kg of FA). Differences
      identified between sampling years were more surprising: compared with that in yr
      2, milk purchased in year 1 had higher concentrations of PUFA (37.5 vs. 32.9 g/kg
      of FA), alpha-LN (6.0 vs. 5.1 g/kg of FA), and linoleic acid (19.9 vs. 17.5 g/kg
      of FA) and lower concentrations of C16:0 and C14:0 (332 vs. 357 and 110 vs. 118
      g/kg of FA, respectively). Strong interactions were identified between management
      and season as well as between season and year of the study. As in the earlier
      farm studies, differences in fat composition between systems were greater for
      summer compared with winter milk. Large between-year differences may be due to
      changes in weather influencing milk composition through forage availability,
      quality, and intake. If climate change predictions materialize, both forage and
      dairy management may have to adapt to maintain current milk quality. Considerable
      variation existed in milk fat composition between brands.

PMID- 21183014
TI  - The effect of sodium chloride substitution with potassium chloride on texture
      profile and microstructure of Halloumi cheese.
AB  - The effect of partial substitution of NaCl with KCl on texture profile and
      microstructure of Halloumi cheese was investigated. Four batches of Halloumi
      cheese were made and kept in 4 different brine solutions (18%, wt/wt), including
      A) NaCl only, B) 3NaCl:1KCl, C) 1NaCl:1KCl, and D) 1NaCl:3KCl and then stored at
      4 degrees C for 56 d. The texture profile was analyzed using an Instron universal
      machine, whereas an environmental scanning electron microscope was used to
      investigate the effect of NaCl substitution on the microstructure of cheeses. No
      significant difference was found in hardness, cohesiveness, adhesiveness, and
      gumminess among experimental cheeses at the same storage day. Hardness,
      cohesiveness, and gumminess decreased significantly during storage period with
      the same salt treatment, whereas adhesiveness significantly increased.
      Environmental scanning electron microscope micrographs showed a compact and
      closed texture for cheeses at the same storage period. The microstructure of all
      cheeses became more closed and compact with storage period. Calcium content
      negatively correlated with hardness and Na and K contents during storage with the
      same salt treatment.

PMID- 21183015
TI  - X-ray microtomography to study the microstructure of cream cheese-type products.
AB  - In this work, the imaging x-ray microtomography technique, new to the field of
      food science, was used for the analysis of fat microstructure and quantification
      of the fat present in cream cheese-type products. Five different types of
      commercially produced cheeses, chosen for their variability of texture, were used
      for this experiment: sample A, sample B, sample C, sample D, and sample E.
      Appropriate quantitative 3-dimensional parameters describing the fat structure
      were calculated (e.g., the geometric parameter percentage of fat volume was
      calculated for each image as a representation of the percentage of total fat
      content within the sample). The dynamic-mechanical properties of these samples
      were also studied using a controlled-strain rotational rheometer. Storage modulus
      and loss modulus were determined in a frequency range of 0.01 to 10 Hz. The
      strain value was obtained by preliminary strain sweep oscillatory trials to
      determine the linear viscoelastic region of the cream cheese-type products.
      Statistical correlation analysis was performed on the results to help identify
      any microstructural-mechanical structure relationships. The results from this
      study show that microtomography is a suitable technique for the microstructural
      analysis of fat in cream cheese-type products, as it does not only provide an
      accurate percentage of the volume of the fat present but can also determine its
      spatial distribution.

PMID- 21183016
TI  - Effect of glycation on sodium caseinate-stabilized emulsions obtained by
      ultrasound.
AB  - This work explores the potential of high-intensity ultrasound to produce fine
      dispersion, long-time-stable, oil-in-water emulsions prepared with native and
      glycated bovine sodium caseinate (SC). Regardless the ultrasound amplitude and
      time assayed, the sonicated emulsions of native SC at 0.5 mg/mL had much higher
      emulsifying activity indexes compared with those emulsions formed by Ultra-Turrax
      (IKA Werke GmbH & Co., Staufen, Germany) homogenization. Nevertheless, the native
      SC emulsions were very unstable despite the optimization of parameters such as
      protein concentration, amplitude of ultrasound wave, and sonication time by using
      a Box-Behnken design. Early glycation of SC with either galactose, lactose, or 10
      kDa dextran substantially improved both emulsifying activity and the stability,
      whereas at advanced stages of glycation, SC emulsions showed notably reduced
      emulsifying properties, likely because extensive glycation of SC promoted its
      polymerization mainly through covalent cross-linking, as was demonstrated by
      particle size measurements. The increase in particle diameter of glycoconjugates
      likely affected the diffusion of SC from bulk to the oil-water interface and
      slowed the reorientation process of the protein at the interface. These findings
      show that the combined effect of early-stage glycation of SC and high-intensity
      ultrasound as an emergent technique to form emulsions has the potential to
      provide improved emulsions that could be used in several food applications.

PMID- 21183017
TI  - Survey of the fatty acid composition of retail milk in the United States
      including regional and seasonal variations.
AB  - Consumers are increasingly aware that food components have the potential to
      influence human health maintenance and disease prevention, and dietary fatty
      acids (FA) have been of special interest. It has been 25 years since the last
      survey of US milk FA composition, and during this interval substantial changes in
      dairy rations have occurred, including increased use of total mixed rations and
      byproduct feeds as well as the routine use of lipid and FA supplements.
      Furthermore, analytical procedures have improved allowing greater detail in the
      routine analysis of FA, especially trans FA. Our objective was to survey US milk
      fat and determine its FA composition. We obtained samples of fluid milk from 56
      milk processing plants across the US every 3 mo for one year to capture seasonal
      and geographical variations. Processing plants were selected based on the
      criteria that they represented 50% or more of the fluid milk produced in that
      area. An overall summary of the milk fat analysis indicated that saturated fatty
      acids comprised 63.7% of total milk FA with palmitic and stearic acids
      representing the majority (44.1 and 18.3% of total saturated fatty acids,
      respectively). Unsaturated fatty acids were 33.2% of total milk FA with oleic
      acid predominating (71.0% of total unsaturated fatty acids). These values are
      comparable to those of the previous survey in 1984, considering differences in
      analytical techniques. Trans FA represented 3.2% of total FA, with vaccenic acid
      being the major trans isomer (46.5% of total trans FA). Cis-9, trans-11 18:2
      conjugated linoleic acid represented 0.55% total milk FA, and the major n-3 FA
      (linolenic acid, 18:3) composed 0.38%. Analyses for seasonal and regional effects
      indicated statistical differences for some FA, but these were minor from an
      overall human nutrition perspective as the FA profile for all samples were
      numerically similar. Overall, the present study provides a valuable database for
      current FA composition of US fluid milk, and results demonstrate that the milk
      fatty acid profile is remarkably consistent across geographic regions and seasons
      from the perspective of human dietary intake of milk fat.

PMID- 21183018
TI  - The effect of bovine milk lactoferrin on human breast cancer cell lines.
AB  - The evidence that biologically active food components are key environmental
      factors affecting the incidence of many chronic diseases is overwhelming.
      However, the full extent of such components in our diet is unknown, as is our
      understanding of their mechanisms of action. Beyond the interaction of these food
      components with the gut and intestinal immune functions, whey proteins such as
      lactoferrin are being tested as anticancer agents. Lactoferrin is an iron-binding
      protein that has been reported to inhibit several types of cancer. In the present
      work, the effects of bovine milk lactoferrin on human breast cancer HS578T and
      T47D cells were studied. The cells were either untreated or treated with
      lactoferrin concentrations ranging from 0.125 to 125 MUM. Lactoferrin decreased
      the cell viability of HS578T and T47D by 47 and 54%, respectively, and increased
      apoptosis about 2-fold for both cell lines. Proliferation rates decreased by 40.3
      and 63.9% for HS578T and T47D, respectively. For the T47D line, cell migration
      decreased in the presence of the protein. Although the mechanisms of action are
      not fully known, the results gathered in this work suggest that lactoferrin
      interferes with some of the most important steps involved in cancer development.

PMID- 21183019
TI  - Expression of nisin genes in cheese--a quantitative real-time polymerase chain
      reaction approach.
AB  - The role of bacteriocins in different environments has not been thoroughly
      explained, mainly because of the difficulties related to the detection of their
      production. Nisin, an antimicrobial peptide produced by Lactococcus lactis has a
      long history of safe use in food products and has been studied from many aspects
      of genetics, biosynthesis, immunity, regulation, and mode of action. Still, some
      aspects concerning the dynamics of nisin gene expression remain unknown,
      especially in complex media like cheese. The main objective of the present study
      was to quantify in a cheese-like medium the expression of nisin genes in L.
      lactis M78, a well-characterized nisin A producer isolated from raw milk. The
      expression of all 11 genes involved in nisin biosynthesis was evaluated during
      cheese production by real-time reverse transcription-PCR. Total RNA was extracted
      from cheeses using a direct extraction method without prior separation of
      microbial cells. The M78 strain grew well in experimental cheeses, producing
      detectable amounts of nisin after 4 h of fermentation. The presence of nisin as
      an activator modified both the expression of nisin genes and the accumulation of
      active nisin. Four groups could be distinguished based on gene expression as a
      function of time: nisA, nisFEG, nisRK and nisBTCIP. Based on nisin-producing
      strain growth, nisin activity, function of nisin genes, and their location,
      correlations were established that contribute to the explanation of regulation of
      nisin biosynthesis and immunity. This study is the first in which the evolution
      of bacteriocin gene transcripts has been quantified rigorously in a cheese-like
      medium.

PMID- 21183020
TI  - Heat stress abatement during the dry period influences metabolic gene expression
      and improves immune status in the transition period of dairy cows.
AB  - Heat stress (HT) and photoperiod affect milk production and immune status of
      dairy cows. The objective was to evaluate the effects of HT abatement prepartum
      under controlled photoperiod on hepatic metabolic gene expression and cellular
      immune function of periparturient Holstein cows (n=21). Cows were dried off 46 d
      before expected calving date and assigned to treatments by mature equivalent milk
      production. The treatments were 1) HT and 2) cooling (CL), both imposed during a
      photoperiod of 14L:10D. Rectal temperature was measured twice daily, whereas
      respiration rate was measured 3 times/wk at 1500 h during the entire dry period.
      After calving, cows were housed in a freestall barn with cooling, and milk yield
      was recorded daily up to 140 d in milk. Liver samples were taken at dry off, -20,
      2, and 20 d relative to calving by biopsy. Under a similar schedule, neutrophil
      function was determined in blood of cows on HT (n=12) and CL (n=9). Blood samples
      were taken on -46, -32, -18, 0, 14, 28, and 42 d relative to calving for
      measurement of metabolites and were collected twice daily from -7 to 2 d relative
      to calving for prolactin (PRL) analysis. The HT cows had greater concentrations
      of PRL at 0 d relative to calving (150 vs. 93; SEM=11 ng/mL) and had higher
      afternoon rectal temperatures (39.4 vs. 39.0; SEM=0.04 degrees C) and elevated
      respiration rates (78 vs. 56; SEM=2 breaths/min) during the prepartum period
      compared with CL cows. Relative to HT cows, CL cows had greater hepatic
      expression of PRL-R, SOCS-3, and CAV-1 mRNA. Neutrophil oxidative burst was
      greater in CL cows relative to HT cows at 2 d (61 vs. 42; SEM=6%) and at 20 d (62
      vs. 49; SEM=5%) relative to calving, and phagocytosis was greater in CL cows at
      20 d (47 vs. 33; SEM=4%) relative to calving compared with HT cows. Humoral
      response, as measured by IgG secretion against ovalbumin challenge, was greater
      for CL cows at -32 d (0.44 vs. 0.33; SEM=0.05 OD) and -21 d (0.60 vs. 0.50+/-0.04
      OD) relative to calving compared with HT cows. These results suggest that HT
      abatement during the dry period improved innate and acquired immune status as
      measured by neutrophil function and immunoglobulin secretion against ovalbumin
      challenge, and altered hepatic gene expression related to PRL signaling in the
      periparturient period or subsequent lactation.

PMID- 21183021
TI  - Restless behavior increases over time, but not with compressibility of the
      flooring surface, during forced standing at the feed bunk.
AB  - Interest in the use of rubber flooring in freestall barns has increased, but
      little is known about which design features of these surfaces are important for
      cattle. In 2 experiments, we evaluated how the type and compressibility of the
      flooring surface in front of the feed bunk influenced the behavioral response to
      4 h of forced standing after morning milking. Two flooring types were compared:
      rubber and concrete. Rubber was tested at 3 levels of compressibility: 2, 4, and
      35 times as compressible as concrete. Four hours of forced standing was evaluated
      because it mimicked conditions that can occur on dairies, particularly when
      waiting for artificial insemination or veterinary treatment. The effects of cow
      weight and hoof surface area, gait score, and hoof health on the response to
      treatment were evaluated. Restless behavior, as measured by number of steps,
      almost doubled over the 4h of forced standing, regardless of flooring material.
      Cows lay down, on average, within 5 min after access to the lying area was
      provided. These results indicate that the 4 h of forced standing was
      uncomfortable. No differences in restless behavior were observed in association
      with the type or compressibility of the flooring surface in front of the feed
      bunk. Cow size, hoof health, or gait score did not consistently explain the
      response to the flooring treatments or stepping rate, although these populations
      of animals were generally healthy. It is unclear if comfort did not differ
      between the flooring options tested during 4 h of forced standing or if
      alterative methodology, such as measuring more subtle shifts in weight, is
      required to assess design features of rubber flooring.

PMID- 21183022
TI  - A retrospective study on the association between different lengths of the dry
      period and subclinical mastitis, milk yield, reproductive performance, and
      culling in Chilean dairy cows.
AB  - The objective of this study was to determine the association between different
      dry period lengths and somatic cell counts, milk yield, reproductive performance,
      and risk of early culling during the subsequent lactation of Chilean dairy cows.
      The length of the dry period was classified into 5 categories: 0 to 30 d, 31 to
      52 d, 53 to 76 d, 77 to 142 d, and 143 to 250 d. Generalized mixed models were
      used and included herd as random effect. Time-to-event analyses were performed
      for evaluation of reproductive performance and culling risk. The odds of
      subclinical mastitis (log linear score, LNSCC>=4.5) during early lactation
      increased with extended dry periods (143 to 250 d) during first, second, and
      third test day compared with the reference dry period of 53 to 76 d [odds ratio
      (OR)=1.27, 1.16, and 1.31, respectively]. Short (0 to 30 d) and extended dry
      periods had a detrimental effect on early lactation and 305-d milk yield compared
      with the reference dry period. Longer dry periods were associated with increased
      number of days for calving-to-first service interval and calving to conception
      interval. Average calving-to-first service interval for short and extended dry
      period were 83 d and 89.4 d, respectively. Average days to conception were 127.8
      d and 131.4 d for a dry period of 31 to 52 d and extended dry period,
      respectively. Similarly, the number of services per conception increased with
      length of previous dry period from 1.62 (31 to 52 d) to 2.44 (143 to 250 d). Cows
      with previous short and extended dry period had higher odds of culling when
      compared with cows in the reference group (OR=2.20 and 1.57, respectively).
      Compared with the reference group, cows in the dry period category 77 to 142 d
      had the highest odds of death followed by the category 143 to 250 d (OR=1.27 and
      1.18, respectively).When death and live culling were combined, the highest odds
      of combined death and culling were for cows in the categories 0 to 30 d and 143
      to 250 d (OR=1.63 and 1.44, respectively). We conclude that extended dry periods
      (143 to 250 d) increase the odds of subclinical mastitis occurrence during early
      lactation and have a negative association with reproductive performance. Short
      and extended dry periods were negatively associated with early lactation and 305
      d milk yield and were related to increased overall culling when compared with the
      reference dry period.

PMID- 21183023
TI  - Characteristics of prolonged luteal phase identified by milk progesterone
      concentrations and its effects on reproductive performance in Holstein cows.
AB  - A database of milk progesterone profiles consisting 497 lactations in 3 dairy
      herds from northern and western regions of Japan was used to identify the
      characteristics and associated risk factors for prolonged luteal phase (PLP) and
      its effects on subsequent reproductive performance in high-producing Holstein
      cows. Milk samples were collected twice weekly and progesterone concentrations in
      whole milk were determined by ELISA. Herds were visited monthly and examined by
      vaginoscopy and transrectal palpation. Resumption of ovarian cyclicity within 35
      d postpartum followed by regular cycles was considered normal. Prolonged luteal
      phase was defined when progesterone concentrations were >=5 ng/mL for >=20 d of
      duration in any cycle postpartum. Delay of first ovulation to 35 to 60 d (delayed
      first ovulation type I), >60 d (delayed first ovulation type II), a luteal phase
      of <14 d except in the first cycle (short luteal phase), and the absence of
      luteal activity >14 d between 2 cycles (cessation of cyclicity) were the other
      categories of abnormal ovarian resumptions considered. The overall incidence of
      PLP in the 3 herds was 11.9% and a significantly higher proportion of PLP was
      observed in the first cycle postpartum compared with the second and third cycles.
      Approximately 83% of the PLP were 20 to 28 d in duration, and maximum
      progesterone concentration was significantly higher when PLP lasted >35 d
      compared with PLP of 20 to 35 d in duration. Higher parity, commencement of
      luteal activity<=28 d postpartum, and postpartum complications significantly
      increased the occurrence of PLP within 90 d postpartum. Cows with PLP showed
      reduced conception rate to first artificial insemination (AI) and reduced
      pregnancy proportions within 100, 150, and 210 d postpartum. Based on survival
      analysis, PLP was associated with a 56% reduction in relative pregnancy rate and
      a 36% reduction in AI submission rate. Cows that experienced PLP had a longer
      interval from calving to first AI (74 d) and from calving to pregnancy (141 d)
      than cows without PLP (53 and 80 d), respectively. In conclusion, 11.9% of
      lactations had PLP, of which approximately two-thirds were seen in the first
      cycle postpartum. Most of the PLP were 20 to 28 d in duration. Higher parity,
      postpartum complications, and early commencement of luteal activity postpartum
      increased the risk for PLP. Occurrence of PLP adversely affected fertility by
      reducing pregnancy proportions and extending calving to conception interval.

PMID- 21183024
TI  - Mastitis diagnostics: quantitative PCR for Staphylococcus aureus genotype B in
      bulk tank milk.
AB  - A novel real-time quantitative PCR assay for detecting the pathogenic and
      contagious Staphylococcus aureus genotype B (GTB) in bulk tank milk was developed
      and evaluated. The detection of this pathogen in bulk tank milk would greatly
      facilitate its control, as it is responsible for great economic loss in Swiss
      dairy herds. The assay is based on the simultaneous detection of 3 GTB-typical
      target sequences, including 2 enterotoxin genes and a polymorphism within the
      leucotoxin E gene. A variety of mastitis-associated bacteria was used to validate
      the assays, resulting in an analytical specificity of 100% and high
      repeatability. The analytical sensitivity in milk was 40 cfu/mL. An exponential
      association between simulated cow prevalence and quantitative PCR result was
      observed. An initial field study revealed 1 GTB-positive herd among the 33
      studied herds. This novel assay for bulk tank milk analysis is suitable for
      routine purposes and is expected to be an effective tool for minimizing Staph.
      aureus GTB in Swiss dairy herds.

PMID- 21183025
TI  - Antimicrobial activity of bovine beta-lactoglobulin against mastitis-causing
      bacteria.
AB  - Bovine mastitis is one of the most economically deleterious diseases affecting
      dairy herds and results from an infection of the udder by pathogenic
      microorganisms such as Staphylococcus aureus, Streptococcus uberis, and
      Escherichia coli. The mammary gland is capable of preventing and combating
      bacterial infection by means of a complex network of innate and adaptive immune
      mechanisms. Lactoferrin is an 86-kDa protein with antibacterial activity that
      plays a role in the mammary gland's defense against infection. beta-Lactoglobulin
      (beta-LG) is an 18-kDa protein that is present in most mammals but is notably
      absent in humans, rodents, and lagomorphs. Different genetic variants of this
      protein exist, with beta-LG A and beta-LG B being the most common. In spite of
      being well studied, the biological function of beta-LG is not thoroughly
      understood, and most noticeably, no reports exist on the effects of the native
      protein on bacterial growth. Hence, the objective of this study was to assess the
      potential antibacterial activity of beta-LG against mastitis agents. To do this,
      we purified beta-LG from normal bovine milk using a mild, nondenaturing method
      and performed in vitro growth inhibition assays with Staph. aureus, E. coli, and
      Strep. uberis. beta-Lactoglobulin inhibited the growth of Staph. aureus and
      Strep. uberis but had no effect on E. coli. The antimicrobial activity against
      Staph. aureus and Strep. uberis was concentration dependent and was elicited by
      the intact protein because Tricine-sodium dodecyl sulfate-PAGE and analytical gel
      filtration chromatography did not reveal the presence of short degradation
      peptides. Analysis of the genetic variants of beta-LG showed that beta-LG A has
      higher inhibitory activity against Staph. aureus and Strep. uberis than beta-LG
      B. Coincubation of beta-LG and lactoferrin resulted in an augmented antibacterial
      activity against Staph. aureus, suggesting an additive effect of the proteins.
      This result, along with the proteins' complementary spectrum of action, suggests
      that beta-LG and lactoferrin may complement each other in the mammary gland's
      defenses against bacterial infection.

PMID- 21183026
TI  - Efficacy of carprofen on conception rates in lactating dairy cows after
      subcutaneous or intrauterine administration at the time of breeding.
AB  - Manipulation of the reproductive tract can cause inflammatory processes in the
      endometrium and release of cytokines and prostaglandins. It has been shown that
      PGF2alpha has direct negative effects on embryonic survival and development.
      Treatment with nonsteroidal antiinflammatory drugs (e.g., ibuprofen lysinate,
      flunixin meglumine) might improve pregnancy rates after embryo transfer in
      recipient heifers. The primary objective of this study was to evaluate the effect
      of a nonsteroidal antiinflammatory drug on reproductive performance in lactating
      dairy cows when administered at the time of first-service artificial insemination
      (AI) based on the hypothesis that uterine manipulation during AI might be
      similarly intense compared with embryo transfer in its effect on prostaglandin
      release. A total of 970 cows (333 primiparous and 637 multiparous) from 17
      Holstein dairy farms were enrolled. On the day of first AI, cows were randomly
      allocated to 1 of 3 treatment groups. Cows of group 1 received 1.4 mg/kg of body
      weight (BW) of carprofen subcutaneously immediately after AI (SC group). In group
      2, 1.4 mg/kg of BW of carprofen was administered into the uterus using a sterile
      disposable catheter 12 to 24 h after AI (IU group). Animals of group 3 remained
      as untreated controls. First AI conception rate was similar for the SC group
      (42.2%) compared with the untreated control group (45.1%). A binary logistic
      regression model for the odds of conception at first AI revealed a negative
      effect of an intrauterine administration of carprofen on conception rate (38.3%).
      Cows allocated to the IU group had a lower likelihood of being pregnant within
      200 d in milk than cows in the control group. In summary, subcutaneous treatment
      with the nonsteroidal antiinflammatory drug carprofen at the time of AI did not
      influence conception rate, whereas an intrauterine administration of carprofen 12
      to 24 h after first AI had a negative effect on first-service conception rate in
      lactating dairy cows.

PMID- 21183027
TI  - Anaphylatoxin C5a-induced toll-like receptor 4 signaling in bovine neutrophils.
AB  - It is well known that signaling in neutrophils through both the complement
      component 5a (C5a) and C5a receptor (C5aR) and the toll-like receptor 4 (TLR4)
      pathways plays an essential role in innate defense. Neutrophil dysfunction, as
      seen during sepsis in severe mastitis during the periparturient period, is
      correlated with elevated concentrations of anaphylatoxin C5a. The aim of the
      current study was to elucidate the effect of C5a on TLR4 signaling in bovine
      neutrophils. Neutrophils were incubated with a high (but physiological) dose of
      purified C5a, and mRNA was extracted from neutrophils at different time points
      postincubation (PI). The incubation with C5a resulted in a biphasic C5aR
      expression profile, a phenomenon that might be explained by internalization (at
      10 min PI) with subsequent reconstitution (starting at 40 min PI) of this
      receptor. The expression of TLR4, as well as its coreceptor, CD14, showed a
      similar biphasic change as observed with C5aR. In addition, changes in the mRNA
      expression levels of several genes belonging to the TLR4 pathway, such as TICAM
      1, IKKalpha, and MAP3K7 were noted. The maximal expression of TLR4, CD14, and
      C5aR mRNA at 80 min PI was accompanied by a peak in IL8 mRNA, indicating that C5a
      is able to induce IL-8 production in neutrophils in vitro without the need of a
      costimulatory factor such as lipopolysaccharide. Moreover, a relatively constant
      expression of RELA was accompanied by increased expression of ATF3, an endogenous
      inhibitor of nuclear factor-kappaB mediated transcription, implying that C5a
      regulates TLR4 signaling and IL-8 synthesis independently. A significant time
      dependent correlation was found between C5aR and TLR4, with the majority of the
      selected TLR4-dependent genes showing a significant correlation with C5aR at 80
      min PI, when C5aR and TLR4 mRNA expression reached its maximum, suggesting
      crosstalk between both receptors. Taken together, this study showed that C5a is
      able to (1) alter the expression of genes belonging to the TLR4 pathway and (2)
      induce IL8 gene expression in bovine neutrophils. In addition, indications for
      cross-talk between complement activation and TLR4 signaling were found in the
      present study.

PMID- 21183028
TI  - Selenomethionine increases proliferation and reduces apoptosis in bovine mammary
      epithelial cells under oxidative stress.
AB  - The decline in mammary epithelial cell number as lactation progresses may be due,
      in part, to oxidative stress. Selenium is an integral component of several
      antioxidant enzymes. The present study was conducted to examine the effect of
      oxidative stress and selenomethionine (SeMet) on morphology, viability,
      apoptosis, and proliferation of bovine mammary epithelial cells (BMEC) in primary
      culture. Cells were isolated from mammary glands of lactating dairy cows and
      grown for 3 d in a low-serum gel system containing lactogenic hormones and 0 or
      100 MUM H2O2 with 0, 10, 20, or 50 nM SeMet. Hydrogen peroxide stress increased
      intracellular H2O2 to 3 times control concentrations and induced a loss of
      cuboidal morphology, cell-cell contact, and viability of BMEC by 25%. Apoptotic
      cell number more than doubled during oxidative stress, but proliferating cell
      number was not affected. Supplementation with SeMet increased glutathione
      peroxidase activity 2-fold and restored intracellular H2O2 to control levels with
      a concomitant return of morphology and viability to normal. Apoptotic BMEC number
      was decreased 76% below control levels by SeMet and proliferating cell number was
      increased 4.2-fold. These findings suggest that SeMet modulated apoptosis and
      proliferation independently of a selenoprotein-mediated reduction of H2O2. In
      conclusion, SeMet supplementation protects BMEC from H2O2-induced apoptosis and
      increased proliferation and cell viability under conditions of oxidative stress.

PMID- 21183029
TI  - Cow-specific treatment of clinical mastitis: an economic approach.
AB  - Under Dutch circumstances, most clinical mastitis (CM) cases of cows on dairy
      farms are treated with a standard intramammary antimicrobial treatment. Several
      antimicrobial treatments are available for CM, differing in antimicrobial
      compound, route of application, duration, and cost. Because cow factors (e.g.,
      parity, stage of lactation, and somatic cell count history) and the causal
      pathogen influence the probability of cure, cow-specific treatment of CM is often
      recommended. The objective of this study was to determine if cow-specific
      treatment of CM is economically beneficial. Using a stochastic Monte Carlo
      simulation model, 20,000 CM cases were simulated. These CM cases were caused by
      Streptococcus uberis and Streptococcus dysgalactiae (40%), Staphylococcus aureus
      (30%), or Escherichia coli (30%). For each simulated CM case, the consequences of
      using different antimicrobial treatment regimens (standard 3-d intramammary,
      extended 5-d intramammary, combination 3-d intramammary+systemic, combination 3-d
      intramammary+systemic+1-d nonsteroidal antiinflammatory drugs, and combination
      extended 5-d intramammary+systemic) were simulated simultaneously. Finally, total
      costs of the 5 antimicrobial treatment regimens were compared. Some inputs for
      the model were based on literature information and assumptions made by the
      authors were used if no information was available. Bacteriological cure for each
      individual cow depended on the antimicrobial treatment regimen, the causal
      pathogen, and the cow factors parity, stage of lactation, somatic cell count
      history, CM history, and whether the cow was systemically ill. Total costs for
      each case depended on treatment costs for the initial CM case (including costs
      for antibiotics, milk withdrawal, and labor), treatment costs for follow-up CM
      cases, costs for milk production losses, and costs for culling. Average total
      costs for CM using the 5 treatments were (US) $224, $247, $253, $260, and $275,
      respectively. Average probabilities of bacteriological cure for the 5 treatments
      were 0.53, 0.65, 0.65, 0.68, and 0.75, respectively. For all different simulated
      CM cases, the standard 3-d intramammary antimicrobial treatment had the lowest
      total costs. The benefits of lower costs for milk production losses and culling
      for cases treated with the intensive treatments did not outweigh the higher
      treatment costs. The stochastic model was developed using information from the
      literature and assumptions made by the authors. Using these information sources
      resulted in a difference in effectiveness of different antimicrobial treatments
      for CM. Based on our assumptions, cow-specific treatment of CM was not
      economically beneficial.

PMID- 21183030
TI  - Effects of differential supplementation of fatty acids during the peripartum and
      breeding periods of Holstein cows: I. Uterine and metabolic responses,
      reproduction, and lactation.
AB  - The objectives were to evaluate the effects of differential timing of
      supplementation of different Ca salts (CS) of fatty acids (FA) on FA profiles of
      cotyledonary-caruncular tissues, metabolic status, uterine health, pregnancy,
      pregnancy losses after 2 artificial inseminations (AI), and milk yield. Holstein
      cows (n=1,380) were assigned randomly to be fed either CS of palm oil (PO) or
      safflower oil (SO) from 30 d prepartum until 30 d postpartum (dpp) and further
      randomized to receive either CS of PO or fish oil (FO) from 30 to 160 dpp.
      Supplementation of CS of FA was at 1.5% of dietary dry matter. Tissues (n=23) and
      blood (n=32) were collected from a subsample of cows. Blood was collected daily
      from parturition to 10 dpp and three times weekly thereafter until 30 dpp for
      analyses of PGF2alpha metabolite, nonesterified FA, beta-hydroxybutyric acid,
      blood urea nitrogen, and glucose. Cows were evaluated once between 8 to 10 dpp
      for cervical discharge type. At 43 dpp, cows received 2 injections of PGF2alpha
      14 d apart, followed 14 d later by injections of GnRH at 7 d before and 56 h
      after an injection of PGF2alpha with AI at 16 h after the second GnRH injection.
      All cows received intravaginally a controlled internal drug-releasing device,
      containing 1.38 g of progesterone, at 18 d after the first AI followed 7 d later
      by removal of the device and injection of GnRH. Nonpregnant cows at 32 d after AI
      were injected with PGF2alpha, followed 56 h later with a GnRH injection and
      second AI 16 h thereafter. Cows diagnosed pregnant after both AI were re-examined
      at 60 d of pregnancy to determine pregnancy losses. Milk weights were recorded
      monthly for all cows. Caruncular n-6:n-3 FA ratio was greater in cows fed SO.
      Plasma concentrations of metabolites and frequency of cervical discharge type did
      not differ between PO- and SO-fed cows. Plasma PGF2alpha metabolite was greater
      in SO-fed cows at 4 and 7 dpp. Pregnancy per AI at 32 and 60 d post first AI was
      not affected by diets, but pregnancy loss was less in FO-fed cows. At second AI,
      pregnancy was greater in FO-fed cows at 32 d and in SO-FO-fed cows at 60 d post
      AI. Pregnancy loss after second AI was not affected by diets. Overall pregnancy
      per AI was greater in cows fed SO followed by FO at 60 d of pregnancy and
      pregnancy loss was reduced in FO-fed cows. Monthly milk yield was greater (0.7
      kg/d) in SO-fed cows. In conclusion, strategic feeding of CS of FA during
      transition and breeding periods can benefit fertility and milk production of
      lactating dairy cows.

PMID- 21183031
TI  - Alternative programs to presynchronize estrous cycles in dairy cattle before a
      timed artificial insemination program.
AB  - The objective was to test potential presynchronization programs applied to cows
      before a timed artificial insemination (TAI) program to increase the percentage
      of cows ovulating in response to both GnRH injections of a TAI program and having
      a functional corpus luteum before the first GnRH injection of the TAI program. At
      calving, cows were blocked by lactation (1 vs. 2+) and assigned randomly to
      receive 1 of 5 presynchronization treatments. Two variants of the standard
      Presynch program were tested in which 2 injections of PGF2alpha were administered
      14 d apart with either 14 d (Pre14; n=122), 12 d (Pre12; n=123), or 10 d (Pre10;
      n=151) intervening before a TAI program was initiated. Two other
      presynchronization programs consisted of administering a progesterone-releasing
      controlled internal drug release (CIDR) insert for 7 d plus PGF2alpha
      administration at insert removal. Insert removal occurred either 10 d (CIDR10;
      n=157) or 3 d (CIDR3; n=117) before a TAI program was initiated. The TAI program
      was a standard Cosynch program [injection of GnRH 7 d before (GnRH-1) and 72 h
      after (GnRH-2) PGF2alpha with TAI administered 72 h after PGF2alpha]. Cosynch
      served as the control (n=157), and cows were assumed to be starting this program
      at random stages of the estrous cycle. From a subset of cows per treatment
      (ranging from 49 to 51 cows each), blood samples were collected from coccygeal
      vessels by using evacuated tubes at d -28, -14, 0 (onset of TAI program), 7, 9,
      14, and 21. Ovarian scans were conducted on d 0, 7, 9, 14, and 21 by transrectal
      ultrasonography. Diameters of follicles and corpus luteum were measured at each
      exam, and ovulation was determined on d 7 (response to GnRH-1 on d 0) and d 14
      (response to GnRH-2 on d 10). Ovulatory incidence after GnRH-1 (47.1 to 67.3%)
      and GnRH-2 (78 to 90.2%) varied but did not differ among treatments. Before GnRH
      1, progesterone concentrations were less in the CIDR3 treatment than in all other
      treatments. Before GnRH-2, progesterone was greater in the CIDR3 treatment than
      in all other treatments. Luteal regression and synchronization rate (successful
      luteolysis and ovulation after GnRH-2) did not differ among treatments. Pregnancy
      rate per AI at 32 and 60 d post TAI was less in CIDR3 cows than in cows in all
      other treatments. None of the Presynch treatments improved key responses
      (ovulation, luteolysis, and synchronization rate) known to improve fertility
      compared with a standard Cosynch program without presynchronization.

PMID- 21183032
TI  - Potential role of adenosine monophosphate-activated protein kinase in regulation
      of energy metabolism in dairy goat mammary epithelial cells.
AB  - The 5'-adenosine monophosphate-activated protein kinase (AMPK) is an energy
      sensor that regulates cellular metabolism. 5'-Adenosine monophosphate-activated
      protein kinase controls glucose and lipid metabolism in skeletal muscle, liver,
      and adipose tissues. The aim of this study was to investigate the effects of AMPK
      on glucose and lipid metabolism in dairy goat mammary epithelial cells. Treatment
      of mammary epithelial cells with an AMPK activator (5-aminoimidazole-4
      carboxamide 1-beta-D-ribofuranoside) dramatically increased glucose uptake and
      glucose transporter-1 mRNA abundance, and decreased levels of glycogen synthase 1
      mRNA. Activation of AMPK also induced an increase in carnitine palmitoyl
      transferase 1 mRNA and decreases in fatty acid synthase and acetyl-CoA
      carboxylase 1 mRNA. These results suggest that AMPK is involved in the regulation
      of energy metabolism in dairy goat mammary epithelial cells.

PMID- 21183033
TI  - Effects of postbreeding gonadotropin treatments on conception rates of lactating
      dairy cows subjected to timed artificial insemination or embryo transfer in a
      tropical environment.
AB  - The objective of experiment 1 was to evaluate the effects of treatments with
      human chorionic gonadotropin (hCG) or GnRH 7 d after induced ovulation on
      reproductive performance of lactating dairy cows submitted to timed artificial
      insemination (TAI) or timed embryo transfer (TET). A total of 834 potential
      breedings were used from 661 lactating Holstein cows (37.3+/-0.3 kg of milk/d).
      Cows had ovulation synchronized and were assigned randomly to receive TAI on d 0
      or TET on d 7. Within each group, cows were assigned randomly to receive on d 7
      no additional treatment (control; nTAI=156; nTET=126), a 100 MUg i.m. injection
      of GnRH (nTAI=155; nTET=124), or a 2,500 IU i.m. injection of hCG (nTAI=151;
      nTET=122). Postbreeding treatment affected the percentages of pregnant cows at
      TET on d 28 (control: 38.1%; GnRH: 52.4%; hCG: 45.1%) and on d 60 (control:
      32.5%; GnRH: 41.1%; hCG: 38.5%), but postbreeding treatment did not affect
      percentages of pregnant cows at TAI on d 28 (control: 30.1%; GnRH: 32.2%; hCG:
      32.4%) or on d 60 (control: 25.6%; GnRH: 27.1%; hCG: 29.8%). The objective of
      experiment 2 was to evaluate the effect of a treatment with GnRH 7 d after TET on
      reproductive performance of lactating dairy cows that received a previous GnRH
      treatment at TET. A total of 285 potential breedings were used from 257 lactating
      Holstein cows (35.1+/-0.8 kg of milk/d). Cows had ovulation synchronized and were
      assigned for TET on d 7. Immediately after TET, all cows were treated with a 100
      MUg i.m. injection of GnRH. On d 14, cows were assigned randomly to receive (G7
      14; n=147) or not (G7; n=138) an additional injection of GnRH. Pregnancy
      diagnosis were performed on d 28 and 60. The additional treatment with GnRH on d
      14 did not affect the percentages of pregnant cows on d 28 (G7: 48.5%; G7-14:
      42.9%) or on d 60 (G7: 39.8%; G7-14: 37.4%). In conclusion, treatment with GnRH
      or hCG 7 d after induced ovulation increased conception rates in lactating dairy
      cows submitted to TET, but not in cows submitted to TAI. Moreover, treatment with
      GnRH 7 d after TET did not enhance reproductive performance of lactating dairy
      cows that received a previous GnRH treatment at TET.

PMID- 21183034
TI  - Process audits versus product quality monitoring of bulk milk.
AB  - Assessment of milk quality is based on bulk milk testing and farm certification
      on process quality audits. It is unknown to what extent dairy farm audits improve
      milk quality. A statistical analysis was conducted to quantify possible
      associations between bulk milk testing and dairy farm audits. The analysis
      comprised 64.373 audit outcomes on 26,953 dairy farms, which were merged with all
      conducted laboratory tests of bulk milk samples 12 mo before the audit. Each farm
      audit record included 271 binary checklist items and 52 attention point variables
      (given to farmers if serious deviations were observed), both indicating possible
      deviations from the desired farm situation. Test results included somatic cell
      count (SCC), total bacterial count (TBC), antimicrobial drug residues (ADR),
      level of butyric acid spores (BAB), freezing point depression (FPD), level of
      free fatty acid (FFA), and milk sediment (SED). Results show that numerous audit
      variables were related to bulk milk test results, although the goodness of fit of
      the models was generally low. Cow hygiene, clean cubicles, hygiene of milking
      parlor, and utility room were positively correlated with superior product
      quality, mainly with respect to SCC, TBC, BAB, FPD, FFA, and SED. Animal health
      or veterinary drugs management (i.e., drug treatment recording, marking of
      treated animals, and storage of veterinary drugs) related to SCC, FPD, FFA, and
      SED. The availability of drinking water was related to TBC, BAB, FFA, and SED,
      whereas maintenance of the milking equipment was related mainly to SCC, FPD, and
      FFA. In summary, bulk milk quality and farm audit outcomes are, to some degree,
      associated: if dairy farms are assessed negatively on specific audit aspects, the
      bulk milk quality is more likely to be inferior. However, the proportion of the
      total variance in milk test results explained by audits ranged between 4 and 13%
      (depending on the specific bulk milk test), showing that auditing dairy farms
      provides additional information but has a limited association with the outcome of
      a product quality control program. This study suggests that farm audits could be
      streamlined to include only relevant checklist items and that bulk milk quality
      monitoring could be used as a basis of selecting farms for more or less frequent
      audits.

PMID- 21183035
TI  - Diagnosing intramammary infections: evaluation of definitions based on a single
      milk sample.
AB  - Criteria for diagnosing intramammary infections (IMI) have been debated for many
      years. Factors that may be considered in making a diagnosis include the organism
      of interest being found on culture, the number of colonies isolated, whether or
      not the organism was recovered in pure or mixed culture, and whether or not
      concurrent evidence of inflammation existed (often measured by somatic cell
      count). However, research using these criteria has been hampered by the lack of a
      "gold standard" test (i.e., a perfect test against which the criteria can be
      evaluated) and the need for very large data sets of culture results to have
      sufficient numbers of quarters with infections with a variety of organisms. This
      manuscript used 2 large data sets of culture results to evaluate several
      definitions (sets of criteria) for classifying a quarter as having, or not having
      an IMI by comparing the results from a single culture to a gold standard
      diagnosis based on a set of 3 milk samples. The first consisted of 38,376 milk
      samples from which 25,886 triplicate sets of milk samples taken 1 wk apart were
      extracted. The second consisted of 784 quarters that were classified as infected
      or not based on a set of 3 milk samples collected at 2-d intervals. From these
      quarters, a total of 3,136 additional samples were evaluated. A total of 12
      definitions (named A to L) based on combinations of the number of colonies
      isolated, whether or not the organism was recovered in pure or mixed culture, and
      the somatic cell count were evaluated for each organism (or group of organisms)
      with sufficient data. The sensitivity (ability of a definition to detect IMI) and
      the specificity (Sp; ability of a definition to correctly classify noninfected
      quarters) were both computed. For all species, except Staphylococcus aureus, the
      sensitivity of all definitions was <90% (and in many cases<50%). Consequently, if
      identifying as many existing infections as possible is important, then the
      criteria for considering a quarter positive should be a single colony (from a
      0.01-mL milk sample) isolated (definition A). With the exception of "any
      organism" and coagulase-negative staphylococci, all Sp estimates were over 94% in
      the daily data and over 97% in the weekly data, suggesting that for most species,
      definition A may be acceptable. For coagulase-negative staphylococci, definitions
      B (2 colonies from a 0.01-mL milk sample) raised the Sp to 92 and 95% in the
      daily and weekly data, respectively. For "any organism," using definition B
      raised the Sp to 88 and 93% in the 2 data sets, respectively. The final choice of
      definition will depend on the objectives of study or control program for which
      the sample was collected.

PMID- 21183036
TI  - Selenium levels in cows fed pasture and concentrates or a total mixed ration and
      supplemented with selenized yeast to produce milk with supra-nutritional selenium
      concentrations.
AB  - Seventy multiparous Holstein-Friesian cows were fed different amounts of pasture
      and concentrates, or a total mixed ration (TMR), for 42 d in mid-lactation to
      test the hypothesis that the concentration of Se in milk would depend on the
      amount of Se consumed, when the Se is primarily organic in nature, regardless of
      the diet of the cows. Of the 70 cows, 60 grazed irrigated perennial pasture at
      daily allowances of either 20 or 40 kg of dry matter (DM)/cow. These cows
      received 1 of 3 amounts of concentrates, either 1, 3, or 6 kg of DM/cow per day
      of pellets, and at each level of concentrate feeding, the pellets were formulated
      to provide 1 of 2 quantities of Se from Se yeast, either about 16 or 32 mg of
      Se/d. The other 10 cows were included in 2 additional treatments where a TMR diet
      was supplemented with 1 kg of DM/d of pellets formulated to include 1 of the 2
      quantities of supplemental Se. Total Se intakes ranged from 14.5 to 35.9 mg/d,
      and of this, the Se-enriched pellets provided 93, 91, and 72% of the Se for cows
      allocated 20 and 40 kg of pasture DM/d or the TMR, respectively. No effects of
      the amount of Se consumed on any milk production variable, or on somatic cell
      count, body weight, and body condition score, for either the pasture-fed or TMR
      fed cows were found. Milk Se concentrations responded quickly to the commencement
      of Se supplementation, reaching 89% of steady state levels at d 5. When milk Se
      concentrations were at steady state (d 12 to 40), each 1mg of Se eaten increased
      the Se concentration of milk by 5.0 MUg/kg (R(2)=0.97), and this response did not
      seem to be affected by the diet of the cows or their milk production. The
      concentration of Se in whole blood was more variable than that in milk, and took
      much longer to respond to change in Se status, but it was not affected by diet at
      any time either. For the on-farm production of Se-enriched milk, it is important
      to be able to predict milk Se concentration from Se input. In our study, type of
      diet did not affect this relationship.

PMID- 21183037
TI  - Dairy cattle prefer shade over sprinklers: effects on behavior and physiology.
AB  - Cattle will readily use shade in warm weather, but less is known about voluntary
      use of sprinklers. We examined preferences of 96 Holstein-Friesian dairy cows
      (milk yield: 12.7+/-3.48 kg per day; mean+/-SD) for sprinklers, shade, or ambient
      conditions after walking 2.0 km or 0.3 km before afternoon milking (n=48
      cows/distance). Each cow was individually tested on 3 consecutive days with a
      different paired choice each day: 1) shade or sprinklers, 2) shade or ambient
      conditions, 3) sprinklers or ambient conditions. Average air temperature during
      testing was 22.3 degrees C. Cows preferred shade over sprinklers (62 vs. 38% +/-
      5.0%; mean +/- SE) and shade over ambient conditions (65 vs. 35% +/- 5.1%; mean+/
      SE). Cows showed no preference between sprinklers and ambient conditions (44% of
      the cows chose sprinklers, SE=5.3%). The preference for shade over sprinklers and
      ambient conditions increased with air temperature, solar radiation, and wind
      speed. Walking distance did not influence the preference for any treatment.
      Respiration rate was decreased most by sprinklers (38% decrease) but also
      decreased in shade and ambient conditions (17 and 13% decrease, respectively;
      standard error of the difference=4.7%). Similarly, surface temperature was
      decreased most by sprinklers (11.4% decrease), compared with that by shade (1.0%
      decrease), or that by ambient conditions (1.4% increase; standard error of the
      difference=1.82%). Furthermore, sprinklers reduced insect avoidance behaviors,
      including number of tail flicks and hoof stamps. In conclusion, dairy cattle
      preferred to use shade in summer despite sprinklers being more efficient in
      decreasing heat load and insect avoidance behavior.

PMID- 21183038
TI  - Determination of ceftiofur derivatives in serum, endometrial tissue, and lochia
      in puerperal dairy cows after subcutaneous administration of ceftiofur
      crystalline free acid.
AB  - Puerperal uterine infections are often associated with decreased reproductive
      performance in dairy cows. Routine treatment protocols include the systemic
      administration of antibiotics. Antibiotic drugs, however, should be administered
      daily over at least 5 d. The objective of this study was to determine
      concentrations of ceftiofur derivatives in serum, endometrial tissue, and lochia
      after subcutaneous administration of ceftiofur crystalline free acid in 6
      clinically healthy puerperal dairy cows with normal parturition. Samples were
      taken immediately before treatment, 2 h after, and then every 24 h over a 7-d
      period. Concentrations of ceftiofur derivatives were quantified using an HPLC
      assay. In serum and endometrial tissue, ceftiofur derivatives could be detected
      above the reported minimum drug concentrations required to inhibit relevant
      pathogens such as Escherichia coli and Arcanobacterium pyogenes over a 7-d
      period. Concentrations of desfuroylceftiofuracetamide at 5 d after administration
      of ceftiofur crystalline free acid were 1.21+/-0.61 MUg/mL in serum, 0.86+/-0.61
      MUg/mg in endometrial tissue, and 0.96+/-1.15 MUg/mL in lochia. In lochia, mean
      concentrations of ceftiofur derivatives also remained above the minimal
      inhibitory concentration of relevant pathogens, but showed greater variations
      between cows.

PMID- 21183039
TI  - Metagenomic analysis of the uterine bacterial microbiota in healthy and metritic
      postpartum dairy cows.
AB  - At present, many bacterial species are validly known as etiological agents of
      dairy cattle metritis, yet the vast uncultured fraction has received no attention
      so far. The purpose of this study was to use culture-independent methods to
      describe and compare the uterine bacterial composition in healthy and metritic
      postpartum Holstein dairy cows. Both group-specific 16S ribosomal DNA PCR
      denaturing gradient gel electrophoresis (DGGE) and clone library sequencing of
      broad-range 16S ribosomal DNA PCR revealed differences in the bacterial
      communities comparing healthy and metritic cows. Bacterial diversity in healthy
      and metritic uteri was greater and more complex than described previously by
      traditional culture methods. Sequences were assigned to 5 major groups
      (Gammaproteobacteria, Firmicutes, Fusobacteria, Bacteroidetes, and Tenericutes)
      and to uncultured bacteria. Additionally, DGGE suggested the presence of
      Actinobacteria. Most clone sequences in the metritic status libraries were
      affiliated with the phylum Fusobacteria. Many components, especially from other
      phyla, have not previously been isolated from cases of metritis. In the clone
      libraries from the healthy status dairy cows, Gammaproteobacteria was the most
      prominent group and most sequences showed high identity with Mannheimia varigena,
      Pasteurella hemolytica, and members of the phylum Tenericutes. Our data showed
      that the uterine bacterial community in postpartum dairy cows differed
      considerably between healthy and metritic cows and described the occurrence of a
      previously unrecognized extent of this diversity in the bovine intrauterine
      microbiota.

PMID- 21183040
TI  - Somatotropic axis and concentrate supplementation in grazing dairy cows of
      genetically diverse origin.
AB  - Supplementing pasture-fed dairy cows with concentrates in early lactation was
      hypothesized to result in an earlier postpartum recoupling of the somatotropic
      axis in New Zealand (NZ)-type Holstein-Friesian dairy cows than in North American
      (NA)-type cows. To test this hypothesis, NA (n=30) and NZ (n=30) cows were
      allocated to 1 of 3 supplementation strategies (0, 3, or 6 kg of dry matter
      concentrate/d) for the first 12 wk of lactation in a completely randomized design
      and a 2*3 factorial arrangement. Production traits and characteristics of the
      somatotropic axis were studied at phenotypic, hormonal, and gene expression
      levels. Milk production and plasma metabolite concentrations were measured
      weekly, and liver was biopsied in wk 1, 4, 8, and 12 postcalving. North American
      cows produced more milk and displayed a larger degree of somatotropic axis
      uncoupling than did NZ cows. This was evident in strain differences in body
      condition score, blood growth hormone, and insulin-like growth factor-1
      concentrations, and hepatic expression of growth hormone receptor-1a. No
      strain*diet interactions were observed for any characteristic of the somatotropic
      axis at either the blood metabolite or gene expression level; however, blood
      insulin concentrations during wk 7 to 11 postpartum increased with concentrate
      supplementation in NZ but not NA cows. These results demonstrate that feeding
      supplements does not result in an earlier recoupling of the somatotropic axis;
      however, the greater blood insulin concentrations with concentrate feeding in NZ
      cows from wk 7 may result in an earlier recoupling in this genetic strain, after
      the period investigated in this study. Further research is required to understand
      differences in insulin control between these genetic strains.

PMID- 21183041
TI  - Effects of trans fatty acids on markers of inflammation in bovine mammary
      epithelial cells.
AB  - Trans fatty acids (tFA) contribute to inflammation. The objective was to
      investigate the effects of tFA on mRNA expression of proinflammatory markers in
      cultured bovine mammary epithelial cells (MAC-T cell line). Bovine mammary
      epithelial cells were grown in Dulbecco's Modified Eagle Medium containing 10%
      fetal bovine serum. Cells were then subcultured in a medium lacking fetal bovine
      serum, to which incremental concentrations (up to 90 MUM) of elaidic acid (trans
      9 C18:1) or linoleidic acid (trans-9, trans-12 C18:2) were added. Bovine serum
      albumin (fatty acid-free) solutions were added and cells were collected at
      specific time points over 48 h. Then, RNA was extracted and converted to
      complementary DNA for quantitative real-time PCR analysis of proinflammatory gene
      expression. Presence of elaidic acid caused increases in mRNA expression of
      interleukin (IL)-1beta (3.4-fold; dose-independently over a 6-h period) and
      intercellular adhesion molecule (ICAM)-1 (up to 1.4-fold) relative to that for
      cells treated with no tFA, whereas expression of IL-6 and IL-8 was reduced 0.75-
      and 0.85-fold, respectively. Presence of linoleidic acid reduced mRNA expression
      of IL-6 and IL-8 relative to that for control (0.95- and 0.87-fold,
      respectively). Trans mono- and dienoic fatty acids upregulated mRNA expression of
      IL-1beta and ICAM-1, whereas expression of IL-6 and IL-8 was downregulated in MAC
      T cells. Because these genes are ultimately involved in inflammation, elaidic or
      linoleidic acid, either directly fed or formed in the rumen during
      biohydrogenation, may alter the risk for mastitis in vivo.

PMID- 21183042
TI  - Milk urea concentration as an indicator of ammonia emission from dairy cow barn
      under restricted grazing.
AB  - Bulk milk urea concentration was evaluated to assess its potential as an
      indicator of ammonia emission from a dairy cow barn in a situation with
      restricted grazing. An experiment was carried out with a herd of, on average, 52
      Holstein-Friesian dairy cows. The cows were housed in a naturally ventilated barn
      with cubicles and a slatted floor, were fed ensiled forages and feed supplements,
      and each day were allowed 8.5 h of grazing. The experiment was a balanced
      randomized block design, replicated 3 times. The experimental factor was the bulk
      milk urea level, which was adjusted to levels of 15, 35, and 55 mg of urea per
      100 g of milk, respectively, by changing the level of nitrogen fertilization of
      the pasture, the herbage mass and grass regrowth age, and the level and type of
      feed supplement. Ammonia emission from the barn was measured using sulfur
      hexafluoride as the tracer gas. Ammonia emission generally increased upon an
      increase in adjusted milk urea levels. A dynamic regression model was used to
      predict ammonia emission from bulk milk urea concentration, temperature, and a
      slurry mixing index. This model accounted for 66% of the total variance in
      ammonia emission and showed that emission increases exponentially with increasing
      milk urea concentration. At levels of 20 and 30 mg of urea per 100 g of milk,
      ammonia emission increased by about 2.5 and 3.5%, respectively, when milk urea
      concentration increased by 1 mg/100 g. Furthermore, emissions from the barn
      increased 2.6% when temperature increased by 1 degrees C. The study showed that
      bulk milk urea concentration is a useful indicator for ammonia emissions from a
      dairy cow barn in a situation with restricted grazing.

PMID- 21183043
TI  - A prospective study of calf factors affecting first-lactation and lifetime milk
      production and age of cows when removed from the herd.
AB  - This prospective study was designed to investigate possible carryover effects of
      calf management practices and how events occurring during the first 16 wk of life
      affect first-lactation and lifetime milk production as well as age when animals
      are removed from production. This is the final of 3 stages in a longitudinal
      study that encompassed 10 yr of data collection. First, management and
      nutritional data were collected in the first 16 wk of life. The second part of
      this study evaluated conditions of animals at the time of first calving as
      affected by calf management, nutrition, and health. Both of these studies have
      been previously reported. This third portion covers the same calf effects on
      lactation performance and age at culling. Observations for the current study were
      collected from on-farm and Dairy Herd Improvement records. The multiple
      imputation technique was used in this analysis to avoid bias due to missing data.
      This study concluded that delivery score, weaning dry matter intake, days of
      illness before 4 mo, days treated before 4 mo, and body weight at first calving
      all had significant effects on first-lactation production of Holsteins. Delivery
      score and grain intake at a young age affected lifetime production. Age at
      culling was only affected by early grain intake in this study.

PMID- 21183044
TI  - Effect of early feed type exposure on diet-selection behavior of dairy calves.
AB  - Dairy cattle exhibit characteristic feeding behavior patterns that may be
      influenced by early experiences. The objective of this study was to determine how
      early exposure to different feed types affects diet selection behavior of dairy
      calves once fed a mixed ration after weaning off milk. Eight Holstein bull calves
      were randomly assigned at birth to a feed exposure treatment: concentrate or
      grass/alfalfa hay, offered ad libitum. All calves were offered 8 L/d of milk
      replacer [1.2 kg of dry matter (DM)] from birth, which was incrementally reduced
      after 4 wk to enable weaning by the end of wk 7. After milk weaning, all calves
      were fed a mixed ration containing (on a DM basis) 60% concentrate and 40%
      grass/alfalfa hay for 9 wk. Intake was recorded daily, and calves were weighed 3
      times/wk. Samples of fresh feed and orts were taken in wk 8, 12, and 16 for
      particle size analysis. The separator had 3 screens (19, 8, and 1.18 mm)
      producing long, medium, short, and fine particle fractions. Sorting of each
      fraction was calculated as actual intake as a percentage of predicted intake.
      Calves exposed to concentrate tended to have greater DM intake than calves
      exposed to hay both before (0.49 vs. 0.16 kg/d) and after weaning off milk (3.3
      vs. 2.6 kg/d). Weights were similar during the milk-feeding stage, but calves
      exposed to concentrate had greater weights overall in the postweaning stage
      (129.8 vs. 112.6 kg). Initially after weaning, calves sorted for familiar feed;
      calves previously exposed to concentrate sorted for short particles (126.4%),
      which were primarily concentrate, whereas calves previously exposed to hay did
      not (94.2%). Calves previously exposed to hay tended to sort for long particles
      (113.4%), which were solely hay, whereas calves previously exposed to concentrate
      sorted against them (56.4%). The sorting observed for short particles was
      associated with consuming a diet with a greater concentration of protein,
      nonfiber carbohydrates, and metabolizable energy, whereas sorting for long
      particles was associated with consuming a diet with a greater concentration of
      neutral detergent fiber. After 4 wk of exposure to the mixed ration, sorting was
      similar between treatments, with calves in both treatment groups sorting for
      short (117.4 and 120.5%) and against long (62.4 and 54.4%) particles, and
      consuming a diet with a similar concentration of nutrients and energy. These
      results indicate that feed familiarity affected initial diet selection
      postweaning, but may not have a lasting effect, with all calves developing
      similar feed-sorting patterns.

PMID- 21183045
TI  - Population structure of rumen Escherichia coli associated with subacute ruminal
      acidosis (SARA) in dairy cattle.
AB  - Previous studies indicated that only subacute ruminal acidosis (SARA), induced by
      feeding a high-grain diet, is associated with an inflammatory response and
      increased abundance of Escherichia coli in the rumen. We hypothesized that
      ruminal E. coli in grain pellet-induced SARA carried virulence factors that
      potentially contribute to the immune activation during SARA. One hundred twenty
      nine E. coli isolates were cultured from the rumens of 8 cows (4 animals per
      treatment) in which SARA had been nutritionally induced by feeding a high-grain
      diet (GPI-SARA) or a diet containing alfalfa pellets (API-SARA). The population
      structure of the E. coli was evaluated with the ABD genotyping system and
      repetitive sequence-based (rep)-PCR fingerprinting. Twenty-five virulence factors
      were evaluated with PCR. Escherichia coli numbers were higher in the GPI-SARA
      treatment than in the API-SARA treatment. The genetic structure of the E. coli
      was significantly different between SARA challenge models. Isolates from GPI
      control (46%), API-control (70%), and API-SARA (53%) were closely related and
      fell into one cluster, whereas isolates from GPI-SARA (54%) grouped separately.
      The ABD typing indicated a shift from an A-type E. coli population to a B1-type
      population only due to GPI-SARA. Of the 25 virulence factors tested, curli fiber
      genes were highly associated with GPI. Curli fibers were first identified in E.
      coli mastitis isolates and are potent virulence factors that induce a range of
      immune responses. Results suggest that under low rumen pH conditions induced by a
      grain diet, there is a burst in the number of E. coli with virulence genes that
      can take advantage of these rumen conditions to trigger an inflammatory response.

PMID- 21183046
TI  - Differential expression of genes in adipose tissue of first-lactation dairy
      cattle.
AB  - Adipose tissue metabolism is an essential factor in establishment of a successful
      lactation, and we have a good understanding of changes in metabolic flux in
      relation to lactation, parity, and diet. However, the mechanisms of control of
      flux are less well understood. To continue our investigations into the control of
      adipose tissue metabolism, we conducted a transcriptomic analysis of adipose
      tissue of dairy cattle in late pregnancy and early lactation. Our objective was
      to determine the changes in gene expression in adipose tissue between 30 d
      prepartum and 14 d in milk in first-lactation animals, and to determine if
      changes in expression were related to practical production variables. Animals
      were Holstein heifers fed the same diet to National Research Council
      requirements, and adipose tissue was biopsied at 30 d prepartum and 14 DIM. Total
      RNA was extracted and used to determine gene expression on a bovine gene array.
      Genes that code for proteins controlling fatty acid transport were highly
      expressed including fatty acid binding proteins (FABP4 and FABP5) and lipoprotein
      lipase. Among those genes increasing in expression were those controlling
      lipolysis, including ADRB2 (52%) and LIPE (23%). Many genes coding for enzymes
      controlling lipogenesis decreased, including SREBP (-25%), TSHSP14 (-30.8%), LPL
      (-48.4%), and ACACA (-63.9%). This gene expression array analysis in adipose
      tissue of lactating dairy cattle identifies several key genes that are components
      of the adaptation to lactation that can be incorporated into models of
      nutritional efficiency and may be amenable to genetic or dietary manipulation.

PMID- 21183047
TI  - Exclusion of dietary sodium bicarbonate from a wheat-based diet: effects on milk
      production and ruminal fermentation.
AB  - Milk production, rumen fermentation, and whole-tract apparent nutrient
      digestibility in response to feeding 20% steam-rolled wheat with or without
      sodium bicarbonate were evaluated in 12 Holstein cows averaging 165+/-16 DIM.
      Cows were fed 1 of 2 isoenergetic and isonitrogenous diets containing either 0 or
      0.75% sodium bicarbonate on a DM basis for 21 d in a crossover design. Rumen
      fluid samples were obtained 18 times during the last 2 d of each period, and
      fecal samples were collected on 12 occasions from d 18 to 21 of each period.
      Removal of sodium bicarbonate from the diet did not affect DMI (21.0 kg/d),
      yields of milk (30.8 kg/d), or milk components (1.16, 1.01, and 1.40 kg/d for
      fat, protein, and lactose, respectively). Whole-tract apparent digestibility of
      DM, CP, ADF, and NDF did not differ between the 2 treatments (75.3, 76.6, 67.2,
      and 63.6%, respectively). The mean rumen pH was 6.24 and was not affected by
      excluding sodium bicarbonate from the diet. Rumen NH3-N (12.31 mg/dL) and lactic
      acid (3.63 mM) concentrations were not different, whereas total volatile fatty
      acids concentration tended to increase when sodium bicarbonate was present in the
      diet (110 vs. 116 mM). However, average concentrations of the individual volatile
      fatty acids, as a proportion of total volatile fatty acids, were not affected by
      treatment. In conclusion, dairy cow diets can include up to 20% steam-rolled
      wheat without the need for added sodium bicarbonate as long as the diets are
      formulated to meet the fiber requirements of the cow.

PMID- 21183048
TI  - Effect of wheat middlings-based total mixed ration on milk production and
      composition responses of lactating dairy ewes.
AB  - The effect of feeding pelleted total mixed ration (TMR) containing wheat
      middlings (WM) from durum wheat (Triticum durum Desf. cv. Appulo) as a corn grain
      substitute on milk yield and composition performance was measured in
      Comisana*Leccese crossbred lactating ewes. Forty ewes were divided into 2 equal
      groups and fed 1 of the 2 experimental diets for 18 wk. The control diet
      contained 255 g of corn/kg of dry matter (DM) as the main starch source, whereas
      the experimental diet contained 500 g of WM/kg of DM. To evaluate the in vivo
      digestibility of pelleted TMR, 4 adult rams were placed in metabolic cages and
      their individual feces and urine were collected. In the performance trial, ewe
      milk yield was recorded daily and individual milk samples were analyzed weekly
      for milk composition and to determine milk renneting parameters. The ewes fed
      both diets showed similar DM, crude protein, and neutral detergent fiber intakes.
      Digestibility of DM, organic matter, and crude protein of the 2 TMR was similar,
      but neutral detergent fiber digestibility was higher in the WM diet. In the
      milking trial, the WM diet increased milk fat percentage and yield but had no
      effect on milk yield, protein, lactose, and clotting properties compared with the
      control diet. Our findings indicate that WM can be fed to lactating ewes as an
      alternative to more traditional concentrate sources such as corn. Feeding 50% of
      WM in a lactation diet supported milking performance in a manner similar a corn
      based diet. Moreover, the results may be applied in countries where corn
      cultivation is adversely affected by the high cost of production.

PMID- 21183049
TI  - Effects of lauric and myristic acids on ruminal fermentation, production, and
      milk fatty acid composition in lactating dairy cows.
AB  - The objectives of this experiment were to investigate the effects of lauric (LA)
      and myristic (MA) acids on ruminal fermentation, production, and milk fatty acid
      (FA) profile in lactating dairy cows and to identify the FA responsible for the
      methanogen-suppressing effect of coconut oil. The experiment was conducted as a
      replicated 3*3 Latin square. Six ruminally cannulated cows (95+/-26.4 DIM) were
      subjected to the following treatments: 240 g/cow per day each of stearic acid
      (SA, control), LA, or MA. Experimental periods were 28 d and cows were refaunated
      between periods. Lauric acid reduced protozoal counts in the rumen by 96%, as
      well as acetate, total VFA, and microbial N outflow from the rumen, compared with
      SA and MA. Ruminal methane production was not affected by treatment. Dry matter
      intake was reduced 35% by LA compared with SA and MA, which resulted in decreased
      milk yield. Milk fat content also was depressed by LA compared with SA and MA.
      Treatment had no effect on milk protein content. All treatments increased milk
      concentration of the respective treatment FA. Concentration of C12:0 was more
      than doubled by LA, and C14:0 was increased (45%) by MA compared with SA.
      Concentration of milk FA<C16 was 20% lower for LA than MA. Concentrations of
      trans 18:1 FA (except trans 12) and CLA isomers were increased by LA compared
      with SA and MA. Overall, the concentrations of saturated FA in milk fat were
      reduced, and that of >C16 FA and MUFA were increased, by LA compared with the
      other treatments. In this study, LA had profound effects on ruminal fermentation,
      mediated through inhibited microbial populations, and decreased DMI, milk yield,
      and milk fat content. Despite the significant decrease in protozoal counts,
      however, LA had no effect on ruminal methane production. Thus, the
      antimethanogenic effect of coconut oil, observed in related studies, is likely
      due to total FA application level, the additive effect of LA and MA, or a
      combination of both. Both LA and MA modified milk FA profile significantly.

PMID- 21183050
TI  - Interactions of monensin with dietary fat and carbohydrate components on ruminal
      fermentation and production responses by dairy cows.
AB  - Variation in milk fat percentage resulting from monensin supplementation to
      lactating dairy cows could be due to altered ruminal fermentation with
      interactions of monensin with ruminal biohydrogenation of fat and ruminal
      carbohydrate availability. The objective of the study was to determine the
      effects of feeding monensin as Rumensin (R) in diets differing in starch
      availability (ground or steam-flaked corn), effective fiber (long or short
      alfalfa hay, LAH or SAH), and 4% fat (F) from distillers grains, roasted
      soybeans, and an animal-vegetable blend on ruminal fermentation characteristics
      and milk production in lactating dairy cows. Six ruminally cannulated lactating
      Holstein cows were used in a balanced 6*6 Latin square design with 21-d periods.
      The cows were fed 6 diets: (1) C=control diet with ground corn and LAH, (2) CR=C
      plus R, (3) CRFL=CR plus F, (4) CRFS=ground corn, R, F, and SAH, (5) SRFL=steam
      flaked corn, R, F, and LAH, and (6) SRFS=steam-flaked corn, R, F, and SAH. Mean
      particle size of LAH was 5.00 mm and 1.36 mm for SAH. All diets were formulated
      to have 21% forage NDF and 40% NFC. The R tended to decrease DMI, decreased milk
      fat yield, and numerically lowered milk fat percentage (3.41 vs. 2.98%). Addition
      of F to R diets did not affect milk fat percentage. By feeding diets containing R
      and F, SAH tended to increase milk fat percentage for the ground-corn diet, but
      SAH tended to decrease milk fat percentage with steam-flaked corn (CRFL+SRFS vs.
      CRFS+SRFL). The steam-flaked corn increased total-tract NDF digestibility (CRFL +
      CRFS vs. SRFL+SRFS; 51.1 vs. 56%). Addition of F with R decreased total VFA
      concentration and increased rumen pH. Fat addition with R decreased rumen NH3N
      and MUN (12.8 vs. 13.9 mg/dL), and SFC decreased NH3N concentration compared with
      ground corn. Although R caused milk fat depression, addition of F did not further
      exacerbate milk fat depression. Fatty acid analysis did not implicate any
      particular biohydrogenation intermediate as the causative factor for the milk fat
      depression.

PMID- 21183051
TI  - Sodium dodecyl sulfate reduces bacterial contamination in goat colostrum without
      negative effects on immune passive transfer in goat kids.
AB  - To investigate the use of sodium dodecyl sulfate (SDS) as a biocide on goat
      colostrum, 2 experiments were performed. In the first, 20 goat colostrum samples
      were divided into 3 aliquots. A different treatment was performed on each
      aliquot: pasteurization (56 degrees C, 30 min) or addition of SDS to a final
      concentration of either 0.1 or 1% (36 degrees C, 10 min). Immunoglobulin G and
      colony-forming units were evaluated before and after treatment. Both
      pasteurization and treatment with 1% SDS significantly reduced the colony-forming
      units in colostrum. Treatment with 0.1% SDS was not effective at reducing the
      colony-forming units in colostrum. The IgG concentration of pasteurized colostrum
      was significantly lower than that of untreated colostrum, whereas treatment with
      1% SDS did not affect the colostrum IgG concentration. In the second experiment,
      the effects of SDS colostrum treatment on immune passive transfer were evaluated.
      Forty goat kids were fed either refrigerated colostrum or colostrum treated with
      1% SDS twice daily for 2 d. Blood samples were obtained at birth and every day
      for 5 d. IgG, IgM, and IgA were measured in blood serum to monitor the passive
      immune transfer process. Creatinine, glucose, total cholesterol, blood urea
      nitrogen, bilirubin, and aspartate transaminase were also monitored to evaluate
      the health of kids. No differences in serum IgG, IgM, IgA, creatinine, glucose,
      total cholesterol, blood urea nitrogen, bilirubin, or aspartate transaminase
      levels were observed between groups. Our findings indicate that SDS is an
      efficient colostrum biocide that, unlike pasteurization, does not affect immune
      passive transfer or goat kid health.

PMID- 21183052
TI  - Effect of rumen-undegradable protein supplementation and fresh forage composition
      on nitrogen utilization of dairy ewes.
AB  - Previous trials with dairy ewes fed stored feeds indicate a positive effect of
      rumen-undegradable protein (RUP) supplementation on milk yield. However, dairy
      sheep production in the United States is primarily based on grazing mixed grass
      legume pastures, which contain a high proportion of rumen-degradable protein. Two
      trials were conducted to evaluate the effects of high-RUP protein supplementation
      and fresh forage composition on milk yield and N utilization of lactating dairy
      ewes fed in confinement or on pasture. In a cut-and-carry trial, 16 multiparous
      dairy ewes in mid-lactation were randomly assigned to 8 pens of 2 ewes each. Pens
      were randomly assigned 1 of 2 protein supplementation treatments, receiving
      either 0.0 or 0.3 kg of a high-RUP protein supplement (Soy Pass, LignoTech USA
      Inc., Rothschild, WI) per day. Within supplementation treatment, pens were
      randomly assigned to 1 of 4 forage treatments, which were applied in a 4*4 Latin
      square design for 10-d periods. Forage treatments included the following
      percentages of orchardgrass:alfalfa dry matter: 25:75, 50:50, 75:25, and 100:0.
      No interactions were observed between supplement and forage treatments.
      Supplementation with a high-RUP source tended to increase milk yield by 9%. Milk
      yield, milk protein yield, milk urea N, and urinary urea N excretion increased
      linearly with increased percentage of alfalfa. Milk N efficiency was greatest on
      the 100% orchardgrass diet. In a grazing trial, 12 multiparous dairy ewes in mid
      lactation were randomly assigned to 3 groups of 4 ewes each. Within group, 2 ewes
      were randomly assigned to receive either 0.0 or 0.3 kg of a high-RUP protein
      supplement (SoyPlus, West Central Cooperative, Ralston, IA) per day. Grazing
      treatments were arranged in a 3*3 Latin square design and applied to groups for
      10-d periods. Ewes grazed paddocks that contained the following percentages of
      surface area of pure stands of orchardgrass:alfalfa: 50:50, 75:25, and 100:0. No
      interactions were found between supplement and forage treatments. Milk yield,
      milk protein yield, and milk urea N increased linearly with increased percentage
      of alfalfa in the paddock. In conclusion, supplementing with high-RUP protein
      tended to increase milk yield and increasing the proportion of alfalfa in the
      diet increased dry matter intake, milk yield, and protein yield of lactating
      dairy ewes fed or grazing fresh forage.

PMID- 21183053
TI  - Evaluation of a system for monitoring rumination in heifers and calves.
AB  - The Hi-Tag electronic rumination-monitoring system (SCR Engineers Ltd., Netanya,
      Israel), based on capturing audio recordings, provides a reasonable measure of
      rumination time in dairy cows, but has not been validated for milk-fed or weaned
      heifers. The objective of this study was to validate the Hi-Tag rumination
      monitoring system in heifers and calves and to assess whether suckling from a
      teat interfered with recording from this system. Assessments of 2 independent
      observers were highly correlated (r=0.99, n=20), indicating that direct visual
      observations provide a useful standard. Measures from the Hi-Tag system were
      validated by comparing values with those from a single human observer, using
      observations from three 2-h intervals from 35 Holstein calves and heifers aged 4,
      6, and 9 wk and 3, 6, and 9 mo, respectively. In 9-mo-old heifers, rumination
      times obtained from the electronic system were highly correlated with visual
      observations (r=0.88, R2=0.77, n=15), and the mean difference was minor (-4+/-8
      min/2-h interval). The accuracy of data from the automated system decreased when
      used on heifers less than 9 mo old. Suckling did not interfere with the
      electronic system (r=-0.1, n=18). These results indicate that the Hi-Tag system
      is an accurate tool for monitoring rumination behavior in Holstein Friesian
      heifers from the age of 9 mo.

PMID- 21183054
TI  - Effect of enlarging the reference population with (un)genotyped animals on the
      accuracy of genomic selection in dairy cattle.
AB  - Genomic selection (GS) permits accurate breeding values to be obtained for young
      animals, shortening the generation interval and accelerating the genetic gain,
      thereby leading to reduced costs for proven bulls. Genotyping a large number of
      animals using high-density single nucleotide polymorphism marker arrays is
      nevertheless expensive, and therefore, a method to reduce the costs of GS is
      desired. The aim of this study was to investigate an influence of enlarging the
      reference population, with either genotyped animals or individuals with predicted
      genotypes, on the accuracy of genomic estimated breeding values. A dairy cattle
      population was simulated in which proven bulls with 100 daughters were used as a
      reference population for GS. Phenotypic records were simulated for bulls with
      heritability equal to the reliability of daughter yield deviations based on 100
      daughters. The simulated traits represented heritabilities at the level of
      individual daughter performance of 0.3, 0.05, and 0.01. Three scenarios were
      considered in which (1) the reference population consisted of 1,000 genotyped
      animals, (2) 1,000 ungenotyped animals were added to the reference population,
      and (3) the 1,000 animals added in scenario 2 were genotyped in addition to the
      1,000 animals from scenario 1. Genotypes for ungenotyped animals were predicted
      with an average accuracy of 0.58. Additionally, an adjustment of the diagonal
      elements of the G matrix was proposed for animals with predicted genotypes. The
      accuracy of genomic estimated breeding values for juvenile animals was the
      highest for the scenario with 2,000 genotyped animals, being 0.90, 0.79, and 0.60
      for the heritabilities of 0.3, 0.05, and 0.01, respectively. Accuracies did not
      differ significantly between the scenario with 1,000 genotyped animals only and
      the scenario in which 1,000 ungenotyped animals were added and the adjustment of
      the G matrix was applied. The absence of significant increase in the accuracy of
      genomic estimated breeding values was attributed to the low accuracy of predicted
      genotypes. Although the differences were not significant, the difference between
      scenario 1 and 2 increased with decreasing heritability. Without the adjustment
      of the diagonal elements of the G matrix, accuracy decreased. Results suggest
      that inclusion of ungenotyped animals is only expected to enhance the accuracy of
      GS when the unknown genotypes can be predicted with high accuracy.

PMID- 21183055
TI  - Lactation curve models for estimating gene effects over a timeline.
AB  - The effects of genes are commonly estimated using random regression models based
      on test-day data and only give a general gene effect. Alternatively, lactation
      curve models can be used to estimate biological and environmental effects, or to
      predict missing test-day data and perform breeding value estimation. This study
      combines lactation curve models and estimation of gene effects to represent gene
      effects in different stages of lactation. The lactation curve models used were
      based on the Wood, Wilmink, and Ali and Schaeffer models. A random regression
      test-day model was used to compare estimated gene effects with the results of
      commonly used models. The well-characterized DGAT1 gene with known effects on
      milk yield, milk fat, and milk protein production was chosen to test this new
      approach in a Holstein-Friesian dairy cattle population. The K232A polymorphism
      and the promoter VNTR (variable number of tandem repeats) of the DGAT1 gene were
      used. All lactation curve models predicted the production curves sufficiently.
      Nevertheless, for predicting genotype effects, the Wilmink curve indicated the
      closest fit to the data. This study shows that the characteristic gene effects
      for DGAT1 genotypes occur after lactation d 40, which might be explained by a
      link to other genes affecting metabolic traits. Furthermore, allele substitution
      effects of allele K of the K232A locus showed that the typical effect of low milk
      and protein yield is due mainly to a lower overall production level, whereas the
      higher fat and protein content is reached by increased production toward its peak
      and fat yield is increased because of a higher production after this peak.
      Predicting gene effects with production curves gives better insight into the
      timeline of gene effects. This can be used to form genetic groups, in addition to
      feeding groups, for managing livestock populations in a more effective way.

PMID- 21183056
TI  - A Bayesian threshold-linear model evaluation of perinatal mortality, dystocia,
      birth weight, and gestation length in a Holstein herd.
AB  - The objective of this research was to estimate genetic parameters for a multiple
      trait evaluation of dystocia (DYS), perinatal mortality (PM), birth weight (BWT),
      and gestation length (GL) in Holsteins. The data included 5,712 calving records
      collected between 1968 and 2005 from the Iowa State University dairy breeding
      herd in Ankeny. The incidence of PM was 8.8% and that of DYS 28.8%; mean BWT was
      40.5 kg, and GL was 279 d. A threshold-linear animal model included the effects
      of year, season, sex of calf, parity, sire group, direct genetic, maternal
      genetic, and maternal permanent environment. Direct heritabilities for DYS, PM,
      BWT, and GL were 0.11 (0.04), 0.13 (0.05), 0.26 (0.04), and 0.51 (0.05),
      respectively. Maternal heritabilities were 0.14 (0.04), 0.15 (0.03), 0.08 (0.01),
      and 0.08 (0.02), for DYS, PM, BWT, and GL, respectively. The heritabilities are
      the posterior means of the Gibbs samples with their standard deviations in
      parentheses. The direct genetic correlation between PM and DYS was estimated at
      0.67 (0.19), whereas the maternal genetic correlation was 0.45 (0.16). Direct and
      maternal PM and DYS are partially controlled by the same genes. Selection on only
      calving ease is not sufficient to control PM. With moderate genetic correlations
      between all 4 traits, BWT and GL should be included with DYS and PM in an
      evaluation of calving performance.

PMID- 21183057
TI  - Estimation of genetic parameters for measures of calf survival in a population of
      Holstein heifer calves from a heifer-raising facility in New York State.
AB  - The objectives of this study were to estimate the genetic parameters of survival
      to weaning and survival to exit for a population of Holstein calves from New York
      State, as well as to associate the estimated breeding values determined in the
      current study with traits from ongoing genetic evaluations used in Canada and the
      United States. Data were recorded for 7,372 heifer calves at a commercial rearing
      facility in New York State from arrival at 1 to 7 d of age for the duration of
      stay at the facility (on average, heifers departed the facility 1 mo before
      calving). Performance and disease up to weaning and mortality before and after
      weaning were recorded. Analyzed data were limited to daughters of sires with at
      least 10 calves originating from farms that had sent a minimum of 5 calves to be
      raised at the facility. As such, calves from 264 sires and 36 herds were studied
      using 2 statistical methods. The first method, calf survival, used a Weibull
      proportional hazards model, with survival defined as age at culling, death, or
      censoring. The second method, a 2-trait sire model, included survival from
      arrival to weaning (SUV1) and survival from weaning to exit (SUV2). Both models
      included fixed effects of arrival weight, serum total protein, weaning weight,
      season and year of birth, and calving ease score. Herd and sire were included as
      random effects. Significant associations among all fixed effects and calf
      survival were observed. In general, very light or heavy weight at arrival, low
      total protein, low weaning weight, and difficult birth increased risk of
      mortality for calves. The heritability of survival from the first method was
      0.063. The heritabilities from the linear model were 0.001 for SUV1 and 0.036 for
      SUV2. The genetic correlation between SUV1 and SUV2 was 0.58. Genetic variance
      was close to zero for survival of calves to weaning, but was greater for survival
      after weaning through the growing period. Breeding values were estimated for SUV1
      and SUV2 and correlated with routinely evaluated traits from Canadian and US
      genetic evaluations. Significant associations between genetic evaluations for
      survival traits and routinely evaluated traits in Canada and the United States
      were found, in particular with conformation body traits, somatic cell score,
      fertility, and longevity.

PMID- 21183058
TI  - Genetic analysis of mastitis data with different models.
AB  - The aim of this study was to analyze different mastitis data sets with different
      statistical models and compare results. Data recording took place on 3 commercial
      milk farms with an average herd size of 3,200 German Holstein cows. Recording
      started in February 1998 and was completed in December 2005. During this period,
      63,540 treatments for clinical mastitis were recorded. Five different data sets
      were analyzed and the number of cows varied between 12,972 and 13,618, depending
      on the data set. Data collection periods contained either the first 50 or the
      first 300 d of lactation. When the data-recording period ended after 50 d of
      lactation, data sets were analyzed with a lactation threshold model (LTM), a
      multiple threshold lactation model (MTLM), and a test-day threshold model (TDTM).
      In the LTM analysis, mastitis was treated as a binary trait coded as 0 (no
      mastitis) or 1 (mastitis), whereas in MTLM mastitis, codes were between 0 and 4,
      depending on the number of estimated days with mastitis. The TDTM treated each
      day as a single observation coded similarly to that of the LTM. When the data
      collection period included the first 300 d of lactation, data sets were analyzed
      with the LTM or MTLM only, because the TDTM was computationally infeasible.
      Mastitis frequencies in LTM data sets were 25.8 and 39.2%, and 26.9 and 39.2% in
      MTLM data sets, when data recording ended after 50 and 300 d of lactation,
      respectively. The mastitis frequency in the TDTM data set was 5.2%. Respective
      heritability estimates of liability to clinical mastitis were 0.08 and 0.09 using
      the LTM, and 0.08 and 0.11 using the MTLM. When the TDTM was used, the estimated
      heritability was 0.15. Rank correlation between breeding values of the different
      data sets ranged between 0.40 and 0.97. Rank correlation between the LTM and MTLM
      were higher (0.78 to 0.97) than those between these 2 models and the TDTM (0.40
      to 0.59).The MTLM combined the positive effects of both the LTM, with respect to
      the size of the data sets, and the TDTM, with respect to the lack of information.

PMID- 21183059
TI  - Genome-wide association study for calving traits in Danish and Swedish Holstein
      cattle.
AB  - A total of 22 quantitative trait loci (QTL) were detected on 19 chromosomes for
      direct and maternal calving traits in cattle using a genome-wide association
      study. Calving performance is affected by the genotypes of both the calf (direct
      effect) and dam (maternal effect). To identify the QTL contributing these effects
      to calving characteristics, we performed a genome-wide association study using a
      mixed-model analysis in Danish and Swedish Holstein cattle. The analysis
      incorporated 2,062 progeny-tested bulls, and 36,387 single nucleotide
      polymorphism markers on 29 bovine autosomes were analyzed for association with 14
      calving traits. Strong evidence for the presence of QTL that affect calving
      traits was observed on chromosomes 4, 6, 12, 18, 20, and 25. The QTL intervals
      were generally smaller than those described in earlier linkage studies. The
      identification of calving trait-associated single nucleotide polymorphisms and
      mapping of the corresponding QTL in small chromosomal regions will facilitate the
      search for candidate calving performance genes and polymorphisms.

PMID- 21183060
TI  - Genetic effects of heat stress on milk yield of Thai Holstein crossbreds.
AB  - The threshold for heat stress on milk yield of Holstein crossbreds under climatic
      conditions in Thailand was investigated, and genetic effects of heat stress on
      milk yield were estimated. Data included 400,738 test-day milk yield records for
      the first 3 parities from 25,609 Thai crossbred Holsteins between 1990 and 2008.
      Mean test-day milk yield ranged from 12.6 kg for cows with <87.5% Holstein
      genetics to 14.4 kg for cows with >=93.7% Holstein genetics. Daily temperature
      and humidity data from 26 provincial weather stations were used to calculate a
      temperature-humidity index (THI). Test-day milk yield varied little with THI for
      first parity except above a THI of 82 for cows with >=93.7% Holstein genetics.
      For third parity, test-day milk yield started to decline after a THI of 74 for
      cows with >=87.5% Holstein genetics and declined more rapidly after a THI of 82.
      A repeatability test-day model with parities as correlated traits was used to
      estimate heat stress parameters; fixed effects included herd-test month-test year
      and breed groups, days in milk, calving age, and parity; random effects included
      2 additive genetic effects, regular and heat stress, and 2 permanent environment,
      regular and heat stress. The threshold for effect of heat stress on test-day milk
      yield was set to a THI of 80. All variance component estimates increased with
      parity; the largest increases were found for effects associated with heat stress.
      In particular, genetic variance associated with heat stress quadrupled from first
      to third parity, whereas permanent environmental variance only doubled. However,
      permanent environmental variance for heat stress was at least 10 times larger
      than genetic variance. Genetic correlations among parities for additive effects
      without heat stress considered ranged from 0.88 to 0.96. Genetic correlations
      among parities for additive effects of heat stress ranged from 0.08 to 0.22, and
      genetic correlations between effects regular and heat stress effects ranged from 
      0.21 to -0.33 for individual parities. Effect of heat stress on Thai Holstein
      crossbreds increased greatly with parity and was especially large after a THI of
      80 for cows with a high percentage of Holstein genetics (>=93.7%). Individual
      sensitivity to heat stress was more environmental than genetic for Thai Holstein
      crossbreds.

PMID- 21183061
TI  - A comparison of dairy cattle breeding designs that use genomic selection.
AB  - Different dairy cattle breeding schemes were compared using stochastic
      simulations, in which the accuracy of the genomic breeding values was dependent
      on the structure of the breeding scheme, through the availability of new
      genotyped animals with phenotypic information. Most studies that predict the gain
      by implementing genomic selection apply a deterministic approach that requires
      assumptions about the accuracy of the genomic breeding values. The achieved
      genetic gain, when genomic selection was the only selection method to directly
      identify elite sires for widespread use and progeny testing was omitted, was
      compared with using genomic selection for preselection of young bulls for progeny
      testing and to a conventional progeny test scheme. The rate of inbreeding could
      be reduced by selecting more sires every year. Selecting 20 sires directly on
      their genomic breeding values gave a higher genetic gain than any progeny testing
      scheme, with the same rate of inbreeding as the schemes that used genomic
      selection for preselection of bulls before progeny testing. The genomic selection
      breeding schemes could reduce the rate of inbreeding and still increase genetic
      gain, compared with the conventional breeding scheme. Since progeny testing is
      expensive, the breeding scheme omitting the progeny test will be the cheapest
      one. Keeping the progeny test and use of genomic selection for preselection still
      has some advantages. It gives higher accuracy of breeding values and does not
      require a complete restructuring of the breeding program. Comparing at the same
      rate of inbreeding, using genomic selection for elite sire selection only gives a
      13% increase in genetic gain, compared with using genomic selection for
      preselection. One way to reduce the costs of the scheme where genomic selection
      was used for preselection is to reduce the number of progeny tested bulls. This
      was here achieved without getting lower genetic gain or a higher rate of
      inbreeding.

PMID- 21183062
TI  - Short communication: Jersey * Holstein crossbreds compared with pure Holsteins
      for production, mastitis, and body measurements during the first 3 lactations.
AB  - Jersey (JE)*Holstein (HO) crossbred cows (n=76) were compared with pure HO cows
      (n=73) for 305-d milk, fat, and protein production, somatic cell score (SCS),
      clinical mastitis, lifetime production, and body measurements during their first
      3 lactations. Cows were in 2 research herds at the University of Minnesota and
      calved from September 2003 to June 2008. Best prediction was used to determine
      actual production for 305-d lactations as well as lifetime production (to 1,220 d
      in the herd after first calving) from test-day observations. During first
      lactation, JE*HO cows and pure HO cows were not significantly different for fat
      plus protein production; however, JE*HO cows had significantly lower fat plus
      protein production during second (-25 kg) and third (-51 kg) lactation than pure
      HO cows. Nevertheless, JE*HO cows were not significantly different from pure HO
      cows for lifetime production or lifetime SCS. The JE*HO cows were not
      significantly different from pure HO cows for SCS and clinical mastitis during
      first and second lactations; however, JE*HO cows tended to have higher SCS (3.79)
      than pure HO cows (3.40), but significantly lower (-23.4%) clinical mastitis
      during third lactation. The JE*HO cows had significantly less hip height, smaller
      heart girth, less thurl width, and less pin width than pure HO cows during the
      first 3 lactations. Furthermore, JE*HO cows had significantly less udder
      clearance from the ground and significantly greater distance between the front
      teats than pure HO cows during their first 3 lactations.

PMID- 21183063
TI  - Interaction of energy balance, feed efficiency, early lactation health events,
      and fertility in first-lactation Holstein, Jersey, and reciprocal F1 crossbred
      cows.
AB  - First-lactation Holstein (HH), Jersey (JJ), and crossbred cows (HJ and JH, with
      sire breed listed first, followed by dam breed) were observed for cumulative
      energy intake (CEI15) and energy used for milk production (CEL15) at wk 15 of
      lactation in addition to recordings of health problems and pregnancy. Cumulative
      energy balance (CEB15) was calculated from CEI15 and estimates of expenditures at
      wk 15 of lactation. Feed efficiency (FE15) was calculated by dividing CEL15 by
      CEI15. Data included 140 cows with 43, 34, 41, and 22 in the HH, HJ, JH, and JJ
      groups, respectively. The first incidence of displaced abomasum (DA), ketosis
      (KET), mastitis (MAST), and metritis (MET) was recorded in the first 100 d of
      lactation with an incidence of the disease coded as 1 and no incidence coded as
      0. Pregnancy (PREG) at d 150 was recorded as 1 if a cow had conceived by d 150
      and 0 if she had not. Logistic regression was used to analyze health and
      fertility with fixed effects in the model including genetic group, linear and
      quadratic effects for age at calving, and year-season of freshening group.
      Pregnancy was analyzed with the same variables and the addition of CEB15. In
      other analyses, CEB15, CEI15, CEL15, and FE15 were response variables with the
      same explanatory variables plus health events (MAST, DA, MET, and KET), where
      each health event was a separate analysis. Genetic group effects were significant
      in the occurrence of MAST and a trend for MET, but were not significant for PREG,
      DA, and KET. Significant odds ratio for MAST was 19.6 for HJ cows when compared
      with that for HH cows. Thus, HJ cows were 19.6 times more likely than HH cows to
      have an incidence of MAST. The trend was for HJ and JH to have a lower odds ratio
      of MET than that of HH. No other genetic group effects were significant in any of
      the disease and PREG models. The linear and quadratic terms for age at calving
      were not significant. An occurrence of MAST decreased FE15 by 5.2+/-2.2%.
      Mastitis also decreased CEI15 and CEL15, but the compensatory reductions left the
      CEB15 unaffected. An occurrence of a DA decreased CEI15 and an incidence of KET
      decreased CEB15.

PMID- 21183064
TI  - Genetic parameters of milking temperament and milking speed in Canadian
      Holsteins.
AB  - The objectives of this study were to estimate genetic parameters of milking
      temperament (MT) and milking speed (MS) in Canadian Holsteins and to examine
      associations of bull proofs of MT and MS with other economically important
      traits. First-lactation data consisted of 1,940,092 and 2,620,175 cows for MT and
      MS, respectively. Milking temperament and MS were recorded on a scale from 1 to 5
      from very nervous to very calm and from very slow to very fast, respectively. The
      linear animal model included the fixed effects of herd-year-season of calving,
      stage of lactation, age at first calving, and the random effects of animal and
      residual. Both single-trait and bivariate analyses were carried out to estimate
      genetic parameters of MT and MS. For genetic parameter estimation, 20,000 records
      from randomly selected herds were used. However, for breeding value estimation,
      all records were included. Heritability values were 0.128 and 0.139 for MT and
      MS, respectively. The genetic correlation between MT and MS was 0.247. Analysis
      of bull proof correlation of MT and MS with other traits indicated that these
      traits were lowly correlated with a wide range of traits such as production,
      reproduction, conformation, and auxiliary traits.

PMID- 21183065
TI  - The impact of land fragmentation on milk production.
AB  - The effect of land fragmentation on agriculture has worried policymakers for a
      long time because it is expected to be a negative effect. Land consolidation
      policies are frequently implemented to soften the degree of land fragmentation.
      However, to the authors' knowledge, no study in the dairy sector has empirically
      analyzed the role of land fragmentation on farm productivity and profits. This
      study helps to fill this gap in the literature by evaluating the effect of land
      fragmentation on milk production. To accomplish this, a stochastic frontier
      production function was estimated. This empirical analysis uses information
      corresponding to a sample of Spanish dairy farms located in a region where dairy
      production is by far the most important agricultural product and land is highly
      fragmented. As policymakers in the region assume that land fragmentation has a
      negative influence on agricultural production, particularly in dairy production,
      a land consolidation process was developed. Thereafter, a simulation analysis was
      carried out to evaluate the increase in profits that could be obtained by
      reducing land fragmentation. The results show that dairy farms could increase
      their profits in a range between 9.4 and 14% by reducing the degree of land
      fragmentation in a proportion similar to that attained by the land consolidation
      process that is being carried out in the region.

PMID- 21183066
TI  - Viable cell yield from active dry yeast products and effects of storage
      temperature and diluent on yeast cell viability.
AB  - Active dry yeast (ADY) products are commonly fed in the dairy industry, but
      research regarding quality control for such products is limited. The objectives
      of this study were to determine yeast viability in field samples relative to
      manufacturers' guarantees (experiment 1), measure the effects of high-temperature
      storage on yeast viability (experiment 1), and determine the effect of vitamin
      trace mineral (VTM) premix on yeast viability (experiment 2). Commercially
      available ADY products were acquired in triplicate through normal distribution
      channels and stored at 4 degrees C upon receipt. Initial samples were evaluated
      for colony-forming units and compared with product label guarantees. Only 1 of
      the 6 products sampled in experiment 1 met product guarantees for all 3 samples.
      To determine effects of storage temperature and duration on viability, ADY
      samples were stored in an incubator at 40 degrees C with ambient humidity for 1,
      2, and 3 mo. High-temperature storage significantly decreased viability over the
      3-mo period; approximately 90% of viable cells were lost each month. Three of the
      5 products sampled in experiment 2 met product guarantees. Fresh samples of 4 of
      these 5 ADY products were mixed in duplicate with ground corn (GC) or a VTM
      premix to achieve a target concentration of 2.2*10(8) cfu/g. For each product, GC
      and VTM samples were stored at ambient temperature (22 degrees C) and at an
      elevated temperature (40 degrees C) for 2 wk. No differences in viable yeast
      count were observed between GC and VTM samples immediately after mixing or after
      storage at ambient temperature. Yeast viability in GC and VTM samples decreased
      during storage at an elevated temperature. There also was a significant
      interaction of diluent and storage temperature; VTM samples had higher cell
      viability than GC samples when subjected to high-temperature storage. Results
      suggest that (1) ADY products failed to consistently meet product guarantees; (2)
      viability of ADY products was greatly diminished during storage at 40 degrees C
      for 2 wk; and (3) the loss in viability at elevated temperatures may be
      attenuated when ADY products are diluted with a premix containing VTM.

PMID- 21183067
TI  - Desirable global assays.

PMID- 21183068
TI  - Duchenne muscular dystrophy models show their age.
AB  - The lack of appropriate animal models has hampered efforts to develop therapies
      for Duchenne muscular dystrophy (DMD). A new mouse model lacking both dystrophin
      and telomerase (Sacco et al., 2010) closely mimics the pathological progression
      of human DMD and shows that muscle stem cell activity is a key determinant of
      disease severity.

PMID- 21183069
TI  - New ways to make old walls: bacterial surprises.
AB  - Two papers in this issue of Cell (Paradis-Bleau et al., 2010 and Typas et al.,
      2010) report that the lipoproteins LpoA and LpoB are required for the synthesis
      of cell walls in Escherichia coli. Attached to the bacterial outer membrane,
      these new cell wall components regulate penicillin-binding proteins located at
      the inner membrane.

PMID- 21183070
TI  - Wnt signaling: multivesicular bodies hold GSK3 captive.
AB  - Two key events in Wnt signal transduction, receptor endocytosis and inactivation
      of Glycogen Synthase Kinase 3 (GSK3), remain incompletely understood. Taelman et
      al. (2010) discover that Wnt signaling inactivates GSK3 by sequestering the
      enzyme in multivesicular bodies, thus linking these two events and providing a
      new framework for understanding Wnt signaling.

PMID- 21183071
TI  - C/EBPbeta controls exercise-induced cardiac growth and protects against
      pathological cardiac remodeling.
AB  - The heart has the ability to grow in size in response to exercise, but little is
      known about the transcriptional mechanisms underlying physiological hypertrophy.
      Adult cardiomyocytes have also recently been proven to hold the potential for
      proliferation, a process that could be of great importance for regenerative
      medicine. Using a unique RT-PCR-based screen against all transcriptional
      components, we showed that C/EBPbeta was downregulated with exercise, whereas the
      expression of CITED4 was increased. Reduction of C/EBPbeta in vitro and in vivo
      resulted in a phenocopy of endurance exercise with cardiomyocyte hypertrophy and
      proliferation. This proliferation was mediated, at least in part, by the
      increased CITED4. Importantly, mice with reduced cardiac C/EBPbeta levels
      displayed substantial resistance to cardiac failure upon pressure overload. These
      data indicate that C/EBPbeta represses cardiomyocyte growth and proliferation in
      the adult mammalian heart and that reduction in C/EBPbeta is a central signal in
      physiologic hypertrophy and proliferation.

PMID- 21183072
TI  - Paternally induced transgenerational environmental reprogramming of metabolic
      gene expression in mammals.
AB  - Epigenetic information can be inherited through the mammalian germline and
      represents a plausible transgenerational carrier of environmental information. To
      test whether transgenerational inheritance of environmental information occurs in
      mammals, we carried out an expression profiling screen for genes in mice that
      responded to paternal diet. Offspring of males fed a low-protein diet exhibited
      elevated hepatic expression of many genes involved in lipid and cholesterol
      biosynthesis and decreased levels of cholesterol esters, relative to the
      offspring of males fed a control diet. Epigenomic profiling of offspring livers
      revealed numerous modest (~20%) changes in cytosine methylation depending on
      paternal diet, including reproducible changes in methylation over a likely
      enhancer for the key lipid regulator Ppara. These results, in conjunction with
      recent human epidemiological data, indicate that parental diet can affect
      cholesterol and lipid metabolism in offspring and define a model system to study
      environmental reprogramming of the heritable epigenome.

PMID- 21183073
TI  - Regulation of peptidoglycan synthesis by outer-membrane proteins.
AB  - Growth of the mesh-like peptidoglycan (PG) sacculus located between the bacterial
      inner and outer membranes (OM) is tightly regulated to ensure cellular integrity,
      maintain cell shape, and orchestrate division. Cytoskeletal elements direct
      placement and activity of PG synthases from inside the cell, but precise
      spatiotemporal control over this process is poorly understood. We demonstrate
      that PG synthases are also controlled from outside of the sacculus. Two OM
      lipoproteins, LpoA and LpoB, are essential for the function, respectively, of
      PBP1A and PBP1B, the major E. coli bifunctional PG synthases. Each Lpo protein
      binds specifically to its cognate PBP and stimulates its transpeptidase activity,
      thereby facilitating attachment of new PG to the sacculus. LpoB shows partial
      septal localization, and our data suggest that the LpoB-PBP1B complex contributes
      to OM constriction during cell division. LpoA/LpoB and their PBP-docking regions
      are restricted to gamma-proteobacteria, providing models for niche-specific
      regulation of sacculus growth.

PMID- 21183074
TI  - Lipoprotein cofactors located in the outer membrane activate bacterial cell wall
      polymerases.
AB  - Most bacteria surround themselves with a peptidoglycan (PG) exoskeleton
      synthesized by polysaccharide polymerases called penicillin-binding proteins
      (PBPs). Because they are the targets of penicillin and related antibiotics, the
      structure and biochemical functions of the PBPs have been extensively studied.
      Despite this, we still know surprisingly little about how these enzymes build the
      PG layer in vivo. Here, we identify the Escherichia coli outer-membrane
      lipoproteins LpoA and LpoB as essential PBP cofactors. We show that LpoA and LpoB
      form specific trans-envelope complexes with their cognate PBP and are critical
      for PBP function in vivo. We further show that LpoB promotes PG synthesis by its
      partner PBP in vitro and that it likely does so by stimulating glycan chain
      polymerization. Overall, our results indicate that PBP accessory proteins play a
      central role in PG biogenesis, and like the PBPs they work with, these factors
      are attractive targets for antibiotic development.

PMID- 21183075
TI  - Essential role of coiled coils for aggregation and activity of Q/N-rich prions
      and PolyQ proteins.
AB  - The functional switch of glutamine/asparagine (Q/N)-rich prions and the
      neurotoxicity of polyQ-expanded proteins involve complex aggregation-prone
      structural transitions, commonly presumed to be forming beta sheets. By analyzing
      sequences of interaction partners of these proteins, we discovered a recurrent
      presence of coiled-coil domains both in the partners and in segments that flank
      or overlap Q/N-rich and polyQ domains. Since coiled coils can mediate protein
      interactions and multimerization, we studied their possible involvement in Q/N
      rich and polyQ aggregations. Using circular dichroism and chemical crosslinking,
      we found that Q/N-rich and polyQ peptides form alpha-helical coiled coils in
      vitro and assemble into multimers. Using structure-guided mutagenesis, we found
      that coiled-coil domains modulate in vivo properties of two Q/N-rich prions and
      polyQ-expanded huntingtin. Mutations that disrupt coiled coils impair aggregation
      and activity, whereas mutations that enhance coiled-coil propensity promote
      aggregation. These findings support a coiled-coil model for the functional switch
      of Q/N-rich prions and for the pathogenesis of polyQ-expansion diseases.

PMID- 21183077
TI  - Meningococcus Hijacks a beta2-adrenoceptor/beta-Arrestin pathway to cross brain
      microvasculature endothelium.
AB  - Following pilus-mediated adhesion to human brain endothelial cells, meningococcus
      (N. meningitidis), the bacterium causing cerebrospinal meningitis, initiates
      signaling cascades, which eventually result in the opening of intercellular
      junctions, allowing meningeal colonization. The signaling receptor activated by
      the pathogen remained unknown. We report that N. meningitidis specifically
      stimulates a biased beta2-adrenoceptor/beta-arrestin signaling pathway in
      endothelial cells, which ultimately traps beta-arrestin-interacting partners,
      such as the Src tyrosine kinase and junctional proteins, under bacterial
      colonies. Cytoskeletal reorganization mediated by beta-arrestin-activated Src
      stabilizes bacterial adhesion to endothelial cells, whereas beta-arrestin
      dependent delocalization of junctional proteins results in anatomical gaps used
      by bacteria to penetrate into tissues. Activation of beta-adrenoceptor
      endocytosis with specific agonists prevents signaling events downstream of N.
      meningitidis adhesion and inhibits bacterial crossing of the endothelial barrier.
      The identification of the mechanism used for hijacking host cell signaling
      machineries opens perspectives for treatment and prevention of meningococcal
      infection.

PMID- 21183076
TI  - Wnt signaling requires sequestration of glycogen synthase kinase 3 inside
      multivesicular endosomes.
AB  - Canonical Wnt signaling requires inhibition of Glycogen Synthase Kinase 3 (GSK3)
      activity, but the molecular mechanism by which this is achieved remains unclear.
      Here, we report that Wnt signaling triggers the sequestration of GSK3 from the
      cytosol into multivesicular bodies (MVBs), so that this enzyme becomes separated
      from its many cytosolic substrates. Endocytosed Wnt colocalized with GSK3 in
      acidic vesicles positive for endosomal markers. After Wnt addition, endogenous
      GSK3 activity decreased in the cytosol, and GSK3 became protected from protease
      treatment inside membrane-bounded organelles. Cryoimmunoelectron microscopy
      showed that these corresponded to MVBs. Two proteins essential for MVB formation,
      HRS/Vps27 and Vps4, were required for Wnt signaling. The sequestration of GSK3
      extended the half-life of many other proteins in addition to beta-Catenin,
      including an artificial Wnt-regulated reporter protein containing GSK3
      phosphorylation sites. We conclude that multivesicular endosomes are essential
      components of the Wnt signal-transduction pathway.

PMID- 21183078
TI  - Nutrition-responsive glia control exit of neural stem cells from quiescence.
AB  - The systemic regulation of stem cells ensures that they meet the needs of the
      organism during growth and in response to injury. A key point of regulation is
      the decision between quiescence and proliferation. During development, Drosophila
      neural stem cells (neuroblasts) transit through a period of quiescence separating
      distinct embryonic and postembryonic phases of proliferation. It is known that
      neuroblasts exit quiescence via a hitherto unknown pathway in response to a
      nutrition-dependent signal from the fat body. We have identified a population of
      glial cells that produce insulin/IGF-like peptides in response to nutrition, and
      we show that the insulin/IGF receptor pathway is necessary for neuroblasts to
      exit quiescence. The forced expression of insulin/IGF-like peptides in glia, or
      activation of PI3K/Akt signaling in neuroblasts, can drive neuroblast growth and
      proliferation in the absence of dietary protein and thus uncouple neuroblasts
      from systemic control.

PMID- 21183080
TI  - SnapShot: Extrinsic apoptosis pathways.

PMID- 21183081
TI  - Annals of Emergency Medicine Journal Club. To shock or not to shock: that is the
      question; is there an answer?

PMID- 21183079
TI  - A tissue-specific atlas of mouse protein phosphorylation and expression.
AB  - Although most tissues in an organism are genetically identical, the biochemistry
      of each is optimized to fulfill its unique physiological roles, with important
      consequences for human health and disease. Each tissue's unique physiology
      requires tightly regulated gene and protein expression coordinated by
      specialized, phosphorylation-dependent intracellular signaling. To better
      understand the role of phosphorylation in maintenance of physiological
      differences among tissues, we performed proteomic and phosphoproteomic
      characterizations of nine mouse tissues. We identified 12,039 proteins, including
      6296 phosphoproteins harboring nearly 36,000 phosphorylation sites. Comparing
      protein abundances and phosphorylation levels revealed specialized,
      interconnected phosphorylation networks within each tissue while suggesting that
      many proteins are regulated by phosphorylation independently of their expression.
      Our data suggest that the "typical" phosphoprotein is widely expressed yet
      displays variable, often tissue-specific phosphorylation that tunes protein
      activity to the specific needs of each tissue. We offer this dataset as an online
      resource for the biological research community.

PMID- 21183082
TI  - Acute abdomen in infant. Meckel's diverticulum and ileo-ileocolic
      intussusception.

PMID- 21183083
TI  - Managing recent-onset atrial fibrillation in the emergency department.

PMID- 21183084
TI  - Selecting rate control for recent-onset atrial fibrillation.

PMID- 21183085
TI  - Update on emerging infections: news from the Centers for Disease Control and
      Prevention. Cryptococcus gattii.

PMID- 21183086
TI  - The perfect shift.

PMID- 21183087
TI  - Tunnel vision.

PMID- 21183088
TI  - Elderly male with cheek swelling. Acute suppurative parotitis.

PMID- 21183089
TI  - Have we killed the golden hour of trauma?

PMID- 21183092
TI  - Predictor of early diagnosis, diagnosis, or progression of acute kidney injury.

PMID- 21183093
TI  - Factors affecting radiation injury.
AB  - INTRODUCTION: During the past several decades, the number of diagnostic tests and
      procedures that require the administration of radiation has increased
      dramatically. Understanding which factors affect radiation injury and how to
      mitigate these to protect patients has become critical for physicians to
      understand. Informed consent for these procedures has to include a discussion of
      the risks of radiation. METHODS: Factors that affect radiation injury, as well as
      ways to mitigate these, are discussed. Informed consent is also reviewed.
      RESULTS: Technical factors of the radiation delivery and patient factors both
      influence the dose of radiation received. Minimizing exposure is critical, and
      close examination of the patient is warranted to diagnose radiation injury. True
      informed consent includes a frank discussion of the radiation risks as well as
      the benefits of the procedure. CONCLUSION: Minimizing patient radiation exposure
      and accurately diagnosing radiation injury are key skills with which any
      physician ordering or performing tests or procedures requiring the use of
      radiation needs to be familiar. Informed consent includes a discussion of the
      risks as well as the benefits of the proposed radiation exposure.

PMID- 21183094
TI  - Standardized graphs and terms for refractive surgery results.

PMID- 21183095
TI  - Globe-fixation system for animal eye practice.
AB  - We designed a globe-fixation system for use with animal eyes for surgical skills
      training. The system core is a cup with an adjustable aperture. Vacuum is exerted
      through the cup to capture the globe at the preequatorial region. The cup rides
      over a hollow base, sliding on its opening spurs. A ballast is screwed to the end
      of the thread of the cup to create tactile feedback and create a tendency to
      return to the primary position. The system provides optimum versatility for the
      practice of anterior segment procedures, namely stability, rotation, a tendency
      to return to the primary position, globe pressure adjustability, and a modifiable
      orbit size. FINANCIAL DISCLOSURE: Disclosures are found in the footnotes.

PMID- 21183096
TI  - Bowl-and-snail technique for soft cataract.
AB  - We describe a technique for the removal of soft cataracts that can be easily
      taught with good reproducibility. Following hydrodissection, nucleus removal
      starts by sculpting a central bowl down to the posterior capsule. The surrounding
      nuclear rim is then broken into a C-shaped mass that can be rotated and
      emulsified simultaneously. The entire procedure is done within the capsular bag
      with minimal stress on the zonules. FINANCIAL DISCLOSURE: Neither author has a
      financial or proprietary interest in any material or method mentioned.

PMID- 21183097
TI  - Optical analysis, reading performance, and quality-of-life evaluation after
      implantation of a diffractive multifocal intraocular lens.
AB  - PURPOSE: To evaluate the reading performance, changes in quality of life, and
      optical performance after cataract surgery with multifocal diffractive
      intraocular lens (IOL) implantation. SETTING: Vissum Corporation, Alicante,
      Spain. DESIGN: Prospective case series. METHODS: Patients with bilateral cataract
      had implantation of Acri.LISA 366D multifocal IOLs. Visual acuity and contrast
      sensitivity outcomes were evaluated during a 6-month follow-up. Other parameters
      evaluated included reading performance (Salzburg Reading Desk), a 25-item quality
      of-life questionnaire (National Eye Institute Visual Functioning Questionnaire-25
      [NEI VFQ-25] and appendix NEI VFQ-39), and ocular optical performance (ocular
      aberrometry and modulation transfer function). RESULTS: The study included 48
      eyes (24 patients) ranging in age from 47 to 77 years. The mean uncorrected
      distance visual acuity (logMAR) improved significantly 1 month postoperatively
      (P<.01), with no significant changes afterward (6 months, P>=.06). The mean
      reading acuity without correction improved significantly from 0.68 logRAD +/-
      0.20 (SD) to 0.16 +/- 0.08 logRAD 1 month after surgery (P < .01). However, it
      was worse by the end of the follow-up (6 months, P = .04). During the follow-up,
      no significant changes were found in the mean reading speed without near
      correction (6 months, P = .50). Contrast sensitivity improved significantly at
      all spatial frequencies under photopic and scotopic conditions after surgery (6
      months, P<=.02). The quality-of-life index related to reading ability also
      improved significantly (3 months, P = .03). CONCLUSION: Implantation of the
      multifocal diffractive IOL significantly improved reading performance, which had
      a positive effect on the patient's quality of life postoperatively. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 21183098
TI  - Reduced effect of glare disability on driving performance in patients with blue
      light-filtering intraocular lenses.
AB  - PURPOSE: To compare the effects of glare on driving performance in patients who
      had implantation of a blue light-filtering acrylic intraocular lens (IOL) and
      those who had implantation of an acrylic IOL with no blue-light filter. SETTING:
      Department of Applied Psychology, Arizona State University, Mesa, Arizona, USA.
      DESIGN: Cross-sectional study. METHODS: Patients with a blue light-filtering
      AcrySof Natural SN60AT IOL (study group) and patients with an AcrySof SA60AT IOL
      with no blue-light filter (control group) who had good visual acuity and a valid
      driver's license performed left-turn maneuvers in a driving simulator in front of
      oncoming traffic. The safety margin (time to collision minus time taken to turn
      at intersection with oncoming traffic) was calculated. The measurements were
      repeated with a glare source simulating low-angle sun conditions (daytime
      driving). RESULTS: With glare, the safety margin was statistically significantly
      greater in the study group (n = 17) than in the control group (n = 17) (mean
      2.534 seconds +/- 0.488 [SD] and 2.116 +/- 0.511 seconds, respectively) (P <
      .05). Comparing no-glare conditions and glare conditions, the study group had
      significantly lower glare susceptibility, fewer collisions with the oncoming car,
      and a lower impact on intersection approach speed than the control group.
      CONCLUSIONS: The IOL incorporating blue light-filtering technology significantly
      reduced glare disability and improved the driver's ability to safely execute a
      left turn with oncoming traffic in the presence of glare simulating low-angle sun
      conditions. The real-world benefit of this technology is presumably mediated by a
      stronger signal to detect approaching objects (motion-in-depth) as a result of a
      reduction in glare disability. FINANCIAL DISCLOSURE: No author has a financial or
      proprietary interest in any material or method mentioned. Additional disclosures
      are found in the footnotes.

PMID- 21183099
TI  - Intraocular lens formula constant optimization and partial coherence
      interferometry biometry: Refractive outcomes in 8108 eyes after cataract surgery.
AB  - PURPOSE: To assess the benefits of intraocular lens (IOL)-constant optimization
      for IOLMaster biometry on refractive outcomes after cataract surgery for all
      surgeons and individual surgeons, define acceptable levels of error in IOL
      constant optimization, and calculate the minimum number of eyes required for IOL
      constant optimization. SETTING: Department of Ophthalmology, Gloucestershire
      Hospitals NHS Foundation Trust, Cheltenham, United Kingdom. DESIGN: Database
      study. METHODS: Hypothetical prediction errors were retrospectively calculated on
      prospectively collected data extracted from electronic medical records using
      manufacturers' and optimized IOL constants with Hoffer Q, Holladay 1, and SRK/T
      formulas for 2 IOLs. The acceptable IOL-constant optimization error margins,
      personalized IOL constants for individual surgeons, and minimum sample sizes for
      IOL-constant optimization were evaluated. RESULTS: Optimization of IOL constants
      reduced the mean absolute errors from 0.66 diopters (D) and 0.52 D to 0.40 D and
      0.42 D for the Sofport AO IOL and Akreos Fit IOL, respectively. The percentage of
      eyes within +/-0.25 D, +/-0.50 D, and +/-1.00 D of target refraction improved
      from for both IOL models. The IOL-constant errors exceeding 0.09 for the Hoffer
      Q, 0.09 for the Holladay 1, and 0.15 for the SRK/T produced inferior outcomes.
      Differences in personalized IOL constants between most surgeons were clinically
      insignificant. Calculating IOL constants to within 0.06, 0.06, and 0.10 for the
      Hoffer Q, Holladay 1, and SRK/T, respectively, required 148 to 257 eyes.
      CONCLUSIONS: Optimizing IOL constants for IOLMaster biometry substantially
      improved refractive outcomes, far exceeding any additional benefit of
      personalizing IOL constants for individual surgeons. FINANCIAL DISCLOSURE: No
      author has a financial or proprietary interest in any material or method
      mentioned. Additional disclosure is found in the footnotes.

PMID- 21183100
TI  - Formula choice: Hoffer Q, Holladay 1, or SRK/T and refractive outcomes in 8108
      eyes after cataract surgery with biometry by partial coherence interferometry.
AB  - PURPOSE: To assess how intraocular lens (IOL) formula choice affects refractive
      outcomes after cataract surgery using IOLMaster biometry. SETTING: Department of
      Ophthalmology, Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, United
      Kingdom. DESIGN: Database study. METHODS: Hypothetical prediction errors were
      retrospectively calculated on prospectively collected data from electronic
      medical records using optimized Hoffer Q, Holladay 1, and SRK/T formulas (Sofport
      AO and Akreos Fit IOLs) across a range of 0.5 mm or 1.0 mm axial length (AL)
      subgroups. RESULTS: In short eyes, the Hoffer Q had the lowest mean absolute
      error (MAE) for ALs from 20.00 to 20.99 mm. The Hoffer Q and Holladay 1 had a
      lower MAE than the SRK/T for ALs from 21.00 to 21.49 mm. There were no
      statistically significant differences in MAE for ALs from 21.50 to 21.99 mm. In
      medium eyes, there were no statistically significant differences in MAE for any
      IOL formula for ALs from 22.00 to 23.49 mm. For ALs from 23.50 to 25.99 mm, there
      was a trend toward lower MAEs for the Holladay 1, with statistically significant
      differences in 2 subgroups. In long eyes, the SRK/T had the lowest MAE, with
      statistically significant differences for ALs of 27.00 mm or longer. CONCLUSIONS:
      The Hoffer Q performed best for ALs from 20.00 to 20.99 mm, the Hoffer Q and
      Holladay 1 for ALs from 21.00 to 21.49 mm, and the SRK/T for ALs of 27.00 mm or
      longer. Using optimized constants, refractive outcomes of 40%, 75%, and 95%
      within +/-0.25 diopter (D), +/-0.50 D, and +/-1.00 D, respectively, were
      achievable. FINANCIAL DISCLOSURE: No author has a financial or proprietary
      interest in any material or method mentioned. Additional disclosure is found in
      the footnotes.

PMID- 21183101
TI  - Accuracy of a dual Scheimpflug analyzer and a corneal topography system for
      intraocular lens power calculation in unoperated eyes.
AB  - PURPOSE: To evaluate the accuracy of the corneal power measurements by a dual
      Scheimpflug analyzer (Galilei) and a corneal topography system (Keratron) for
      intraocular lens (IOL) power calculation in unoperated eyes. SETTING: Private
      practice. DESIGN: Case series. METHODS: The IOL power was calculated for eyes
      having phacoemulsification and in-the-bag IOL implantation by entering into the
      Hoffer Q, Holladay 1, and SRK/T formulas 3 corneal power measurements: (1)
      simulated keratometry (K) by corneal topography, (2) simulated K derived by
      anterior corneal curvature only using the dual Scheimpflug analyzer, (3) total
      corneal power derived by anterior and posterior corneal curvatures through ray
      tracing using the dual Scheimpflug analyzer. The prediction error was calculated
      as the difference between the predicted and the measured refraction 1 month
      postoperatively. RESULTS: Forty-three consecutive patients were enrolled. The
      mean arithmetic error was zero for all combinations of measurements due to
      constant optimization. Using the Hoffer Q formula, the mean absolute prediction
      errors were 0.23 diopters (D) +/- 0.22 (SD) for the corneal topographer simulated
      K, 0.21 +/- 0.18 D for the Scheimpflug simulated K, and 0.27 +/-0.20 D for the
      Scheimpflug total corneal power (P>.05). No statistically significant different
      results (compared with the Hoffer Q formula) were obtained with the Holladay 1
      and SRK/T formulas. CONCLUSIONS: Both devices provided corneal power measurements
      that led to accurate IOL power calculation. The total corneal power by the dual
      Scheimpflug system is the first corneal power measurement shown to lead to
      accurate IOL power calculation without using the standard keratometric index.
      FINANCIAL DISCLOSURE: Drs. Savini, Barboni, and Carbonelli have no financial or
      proprietary interest in any material or method mentioned. Additional disclosures
      are found in the footnotes.

PMID- 21183102
TI  - Morphologic changes in the anterior chamber in patients with cortical or nuclear
      age-related cataract.
AB  - PURPOSE: To assess and compare the morphologic changes in the anterior segment in
      eyes with nuclear or cortical age-related cataract using Scheimpflug imaging.
      SETTING: Peking University People's Hospital, Beijing, China. DESIGN: Case
      control study. METHODS: Patients with nuclear or cortical age-related cataract
      were recruited. The grade of nuclear opalescence or cortical opacity was assessed
      using the Lens Opacities Classification System III (LOCS III). A group of elderly
      subjects with a clear lens and normal vision served as the control group.
      Anterior chamber depth (ACD), anterior chamber volume (ACV), and lens thickness
      were evaluated using Scheimpflug imaging (Pentacam). RESULTS: Two hundred sixty
      nine patients (330 eyes) were recruited. Thirty eyes were enrolled for each
      nuclear opalescence and cortical grade. The control group comprised 30 eyes (19
      subjects). In eyes with age-related cataract, lens thickness increased with an
      increase in cortical opacity, whereas the ACD and ACV values decreased. The ACD
      was inversely correlated with LOCS III grades for nuclear opalescence (r = 
      0.197, P = .004), nuclear color (r = -0.195, P = .005), and cortical opacity (r =
      -0.508, P<.005). There were significant differences in lens thickness, ACD, and
      ACV between nuclear color, nuclear opalescence, and cortical opacity for LOCS III
      grades 3, 4, and 5, respectively. CONCLUSIONS: There were significant differences
      in lens thickness, ACD, and ACV between nuclear and cortical age-related
      cataracts. The ACD decreased more in eyes with cortical cataract, suggesting that
      the risk for angle-closure glaucoma may be greater in cases of cortical opacity
      in which lens expansion is greater. FINANCIAL DISCLOSURE: No author has a
      financial or proprietary interest in any material or method mentioned.

PMID- 21183103
TI  - Visual axis opacification after cataract surgery and hydrophobic acrylic
      intraocular lens implantation in the first year of life.
AB  - PURPOSE: To report the incidence of visual axis opacification (VAO) requiring
      surgery after cataract extraction with hydrophobic acrylic intraocular lens (IOL)
      implantation during the first year of life. SETTING: Storm Eye Institute,
      Charleston, South Carolina, USA; Iladevi Cataract and IOL Research Center,
      Ahmedabad, India. DESIGN: Cohort study. METHODS: Medical records of patients
      younger than 1 year who had primary posterior capsulectomy, vitrectomy, and in
      the-bag hydrophobic acrylic IOL implantation were reviewed. In bilateral cases, 1
      eye was randomly chosen. The need for surgery for visually significant VAO was
      evaluated 12 months after cataract surgery. RESULTS: Seventy-two eyes were
      included. The mean age at cataract surgery was 6.0 months. Seventeen eyes (23.6%)
      required surgery for VAO a mean of 6.2 +/- 2.9 months postoperatively. The odds
      for VAO surgery were 3.5 times greater in eyes of female children than in eyes of
      male children. For AcrySof MA60AC, SA60AT, SN60AT, or SN60WF IOLs, surgery for
      VAO was required in 25%, 23%, 23%, and 23% of eyes, respectively. The earliest
      time between cataract and secondary VAO surgery was relatively later (9.0 months)
      with the SN60WF IOL than with the MA60AC, SA60AT, or SN60AT IOL (4.4, 2.2, and
      2.0 months, respectively). CONCLUSIONS: Nearly 25% of operated eyes of infants
      required a secondary surgical procedure for VAO; the rate was higher in eyes of
      female infants but did not differ between IOL models. The data indicate that
      surgery for VAO is required later in eyes with an SN60WF IOL than in eyes in
      which other AcrySof IOLs were used. FINANCIAL DISCLOSURE: No author has a
      financial or proprietary interest in any material or method mentioned.

PMID- 21183104
TI  - Posterior capsule opacification in eyes with steroid-induced cataracts:
      Comparison of early results.
AB  - PURPOSE: To evaluate posterior capsule opacification (PCO) development after
      cataract surgery in eyes with or without a history of steroid use. SETTING:
      Iladevi Cataract & IOL Research Centre, Ahmedabad, India. DESIGN: Comparative
      case series. METHODS: This study comprised consecutive patients with a history of
      steroid intake (oral, inhaled, injectable, or topical) for at least 4 months who
      developed posterior subcapsular cataract (PSC) (study group) and patients without
      a history of steroid intake with uncomplicated PSC (control group). Standardized
      surgery was performed in both groups. Digital retroillumination photographic
      documentation was performed 1 month and 1 year postoperatively. The digital
      images were analyzed for PCO using Evaluation of Posterior Capsule Opacification
      (EPCO) software; the entire intraocular lens (IOL) optic and the central 3.0 mm
      optic area were evaluated. The EPCO score and EPCO area were determined. RESULTS:
      One year postoperatively, the mean EPCO score was statistically significantly
      higher in the study group (n = 30) than in the control group (n = 60) (0.33 +/-
      0.37 [SD] versus 0.15 +/- 0.26), as was the mean EPCO area (0.323 +/- 0.36 versus
      0.15 +/- 0.26) (both P<.04). Within the central 3.0 mm optic area, the mean EPCO
      scores (0.149 +/- 0.309 versus 0.003 +/- 0.016 P<.04) and mean EPCO area values
      (0.149 +/- 0.309 versus 0.003 +/- 0.016) were statistically significantly higher
      in the study group (P<.04). CONCLUSION: Steroid-induced PSC was associated with a
      higher risk for PCO after cataract surgery at the 1-year follow-up. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 21183105
TI  - Biocompatibility of hydrophilic acrylic, hydrophobic acrylic, and silicone
      intraocular lenses in eyes with uveitis having cataract surgery: Long-term follow
      up.
AB  - PURPOSE: To evaluate the long-term uveal and capsular biocompatibility of 5
      intraocular lenses (IOLs) in eyes with uveitic cataract. SETTING: Department of
      Ophthalmology, Medical University of Vienna, Vienna, Austria. DESIGN: Comparative
      case series. METHODS: Patients with uveitis of various origin were consecutively
      recruited for cataract surgery (1998-2006) and received 1 of 3 hydrophilic
      acrylic IOLs (Hydroview, AcrySof MA60BM, or Injectacryl F3000), a silicone IOL
      (CeeOn 911), or a hydrophilic acrylic IOL with heparin surface modification
      (BioVue(3)). A 7-year follow-up was performed in the Hydroview, AcrySof, and
      CeeOn groups. Visual acuity, anterior chamber flare measurements, specular
      microscopy, biomicroscopy, and fundoscopy were performed postoperatively at 6
      months and 1, 2, and 3 years. RESULTS: The study enrolled 136 eyes of 115
      patients. There were no significant differences in anterior chamber flare results
      between the 5 groups. The Hydroview group had the highest grade and the CeeOn IOL
      and AcrySof groups had the lowest grade of posterior capsule opacification. The
      BioVue(3) and Injectacryl IOLs had good uveal biocompatibility. Patients in all
      groups had better visual acuity postoperatively. CONCLUSIONS: Overall, patients
      with uveitis benefited from cataract surgery. The long-term results indicate that
      all sharp-edged hydrophilic and hydrophobic IOLs performed well in eyes with
      uveitis. Higher uveal biocompatibility was achieved with the modern hydrophilic
      acrylic IOLs than with the hydrophobic acrylic IOL. Modern hydrophilic acrylic
      IOLs seem to be a good option in these cases. FINANCIAL DISCLOSURE: No author has
      a financial or proprietary interest in any material or method mentioned.

PMID- 21183106
TI  - Randomized comparison of postoperative use of hydrogel ocular bandage and
      collagen corneal shield for wound protection and patient tolerability after
      cataract surgery.
AB  - PURPOSE: To compare the safety and efficacy of a hydrogel bandage and a collagen
      corneal shield in providing wound protection and relief of pain/discomfort in the
      acute period after uneventful unilateral clear corneal phacoemulsification
      cataract surgery with foldable intraocular lens (IOL) implantation. SETTING:
      Seventeen investigational sites in the United States. DESIGN: Prospective
      randomized single-masked parallel study. METHODS: The study comprised patients
      scheduled to have unilateral clear corneal cataract surgery with posterior
      chamber intraocular lens implantation. The patients were examined preoperatively
      and frequently for 30 days postoperatively. The design was a noninferiority study
      of the 2 primary endpoints, device performance and maximum reported postoperative
      pain. RESULTS: The device performance success was 78.6% (228/290) for the
      hydrogel bandage and 26.5% (26/98) for the corneal shield (P<.0001 for
      noninferiority). Analyses indicated that the hydrogel bandage was superior to the
      corneal shield in device performance (P<.001; difference = 52.1%; 95% confidence
      interval, 41.6%-61.4%). The maximum postoperative pain/discomfort score of the
      hydrogel bandage (mean 1.3 +/- 1.8 [SD]; scale 0 to 10) was noninferior to that
      of the corneal shield (1.1 +/- 1.6) in the first 4 hours after surgery (P<.001).
      Adverse events in the cataract surgeries were reported in 22.2% (70/316) and
      36.5% (38/104) of hydrogel bandage patients and corneal shield patients,
      respectively (P = .0045). CONCLUSION: The hydrogel bandage was safe and effective
      for ocular surface protection and relief of pain/discomfort when applied
      topically to clear corneal incisions used in cataract or IOL implantation
      surgery. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest
      in any material or method mentioned. Additional disclosures are found in the
      footnotes.

PMID- 21183107
TI  - Deep anterior lamellar keratoplasty with phacoemulsification.
AB  - PURPOSE: To evaluate the technique and outcomes of deep anterior lamellar
      keratoplasty (DALK) combined with phacoemulsification for corneal opacity with
      coexisting cataract. SETTING: Cornea Service, Dr. Rajendra Prasad Centre for
      Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
      DESIGN: Cohort study. METHODS: Eyes with cataract of varied nucleus grade and
      with different corneal pathologies were selected. Modified triple procedures were
      performed in all eyes. RESULTS: Twenty eyes were evaluated. The corrected
      distance visual acuity (CDVA) after 3 months was 20/60 or better in 18 eyes. One
      eye had 20/80 CDVA as a result of perioperative and postoperative complications.
      One graft became opaque after postoperative infection. CONCLUSION: Simultaneous
      DALK with phacoemulsification was feasible in eyes with coexisting corneal and
      lenticular pathology, and the outcomes were encouraging. FINANCIAL DISCLOSURE: No
      author has a financial or proprietary interest in any material or method
      mentioned.

PMID- 21183108
TI  - Results of small incision lenticule extraction: All-in-one femtosecond laser
      refractive surgery.
AB  - PURPOSE: To report the clinical results of small incision lenticule extraction to
      correct refractive errors using a femtosecond laser to refine the femtosecond
      lenticule extraction technique. SETTING: Private laser center, Vadodara, India.
      DESIGN: Prospective clinical study. METHODS: The VisuMax femtosecond laser system
      was used to perform small incision lenticule extraction to treat refractive
      errors. The laser was used to cut a refractive lenticule intrastromally to
      correct myopia and myopic astigmatism. The lenticule was then extracted from the
      stroma through a 3.0 to 5.0 mm incision. Outcome measures were corrected distance
      visual acuity (CDVA), uncorrected distance visual acuity (UDVA), and manifest
      refraction during 6 months of follow-up. Corneal topography and ocular wavefront
      aberrations were also measured. RESULTS: The study enrolled 51 eyes of 41
      patients. The mean spherical equivalent was -4.87 diopters (D) +/- 2.16 (SD)
      preoperatively and +0.03 +/- 0.30 D 6 months postoperatively. Refractive
      stability was achieved within 1 month (P<.01). Six months after surgery, 79% of
      all full-correction cases had a UDVA of 20/25 or better. The 6-month
      postoperative CDVA was the same as or better than the preoperative CDVA in 95% of
      eyes. Two eyes lost 1 line of CDVA. CONCLUSION: All-in-one femtosecond refractive
      correction using a small incision technique was safe, predictable, and effective
      in treating myopia and myopic astigmatism. FINANCIAL DISCLOSURE: No author has a
      financial or proprietary interest in any material or method mentioned. Additional
      disclosure is found in the footnotes.

PMID- 21183109
TI  - Flap thickness variation with 3 types of microkeratome heads.
AB  - PURPOSE: To determine flap thickness variation with 3 types of microkeratome
      heads and identify the potential factors that affect flap thickness. SETTING:
      Ruijin Hospital, Department of Ophthalmology, Shanghai, China. DESIGN:
      Comparative case series. METHODS: Laser in situ keratomileusis was performed
      using the Moria microkeratome with the One Use-Plus SBK, M2 90, or M2 110 head.
      Flap thickness was calculated by subtraction pachymetry. Age, central corneal
      thickness (CCT), spherical equivalent refraction, mean keratometry, and
      horizontal corneal diameter were recorded preoperatively. RESULTS: The study
      comprised 180 eyes of 90 patients; 60 eyes were treated with each head. The
      difference in mean flap thickness between right and left eyes was not significant
      in the SBK group (97.50 MUm +/- 11.39 [SD] versus 96.73 +/- 10.45 MUm; P = .44)
      but was significant in the M2 90 group (128.03 +/- 12.03 MUm versus 123.40 +/-
      12.38 MUm; P = .0071) and the M2 110 group (140.53 +/- 15.14 MUm versus 135.23 +/
      18.03 MUm, P = .0035). The difference from the intended flap thickness (right
      eyes and left eyes) was 2.50 +/- 11.39 MUm and 3.27 +/- 10.45 MUm, respectively,
      in the SBK group; -8.03 +/- 12.03 MUm and -3.40 +/- 12.38 MUm, respectively, in
      the M2 90 group; and -0.53 +/- 15.14 MUm and 4.77 +/- 18.03 MUm, respectively, in
      the M2 110 group. Flap thickness was positively correlated with baseline CCT in
      each group. CONCLUSIONS: Flap thickness was positively correlated with the
      preoperative CCT using the Moria microkeratome. The SBK head demonstrated the
      most accurate flap thickness, followed by the M2 90 head and the 110 head.
      FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any
      material or method mentioned.

PMID- 21183110
TI  - Corneal collagen crosslinking for keratoconus and corneal ectasia: One-year
      results.
AB  - PURPOSE: To evaluate 1-year outcomes of corneal collagen crosslinking (CXL) for
      treatment of keratoconus and corneal ectasia. SETTING: Cornea and refractive
      surgery subspecialty practice. DESIGN: Prospective randomized controlled clinical
      trial. METHODS: Collagen crosslinking was performed in eyes with keratoconus or
      ectasia. The treatment group received standard CXL and the sham control group
      received riboflavin alone. Principal outcomes included uncorrected (UDVA) and
      corrected (CDVA) distance visual acuities, refraction, astigmatism, and
      topography-derived outcomes of maximum and average keratometry (K) value.
      RESULTS: The UDVA improved significantly from 0.84 logMAR +/- 0.34 (SD) (20/137)
      to 0.77 +/- 0.37 logMAR (20/117) (P = .04) and the CDVA, from 0.35 +/- 0.24
      logMAR (20/45) to 0.23 +/- 0.21 logMAR (20/34) (P<.001). Fifteen patients (21.1%)
      gained and 1 patient lost (1.4%) 2 or more Snellen lines of CDVA. The maximum K
      value decreased from baseline by 1.7 +/- 3.9 diopters (D) (P<.001), 2.0 +/- 4.4 D
      (P = .002), and 1.0 +/- 2.5 D (P = .08) in the entire cohort, keratoconus
      subgroup, and ectasia subgroup, respectively. The maximum K value decreased by
      2.0 D or more in 22 patients (31.0%) and increased by 2.0 D or more in 3 patients
      (4.2%). CONCLUSIONS: Collagen crosslinking was effective in improving UDVA, CDVA,
      the maximum K value, and the average K value. Keratoconus patients had more
      improvement in topographic measurements than patients with ectasia. Both CDVA and
      maximum K value worsened between baseline and 1 month, followed by improvement
      between 1, 3, and 6 months and stabilization thereafter. FINANCIAL DISCLOSURE: No
      author has a financial or proprietary interest in any material or method
      mentioned. Additional disclosure is found in the footnotes.

PMID- 21183111
TI  - Adhesion of laser in situ keratomileusis-like flaps in the cornea: Effects of
      crosslinking, stromal fibroblasts, and cytokine treatment.
AB  - PURPOSE: To evaluate 3 approaches, both cellular and acellular, to improve the
      healing of laser in situ keratomileusis flaps in bovine corneas. SETTING: School
      of Optometry and Vision Sciences and Cardiff Institute of Tissue Engineering and
      Repair, Cardiff University, Cardiff, United Kingdom. DESIGN: Experimental study.
      METHODS: Laser in situ keratomileusis-like flaps were created in bovine corneas,
      and the flap bed was treated with tumor necrosis factor-alpha, interleukin
      1alpha, Fas ligand, transforming growth factor-beta(1), or activated stromal
      fibroblasts. In separate experiments, flaps were created and repositioned. The
      corneas were then crosslinked using ultraviolet-A (UVA) light. All samples were
      then placed in organ culture for up to 4 weeks. Untreated samples acted as
      controls. RESULTS: All treatments increased the adherence of the stromal flap.
      This was achieved at the expense of corneal clarity except in the case of
      crosslinking (CXL). In this case, the flap adhesion force immediately increased
      while the cornea remained clear. The force then decreased gradually during organ
      culture, although it remained at twice the level of the control corneas after 3
      weeks in culture. CONCLUSIONS: The results suggest that riboflavin-UVA CXL is a
      hopeful approach for increasing the adherence strength of corneal flaps while
      keeping the cornea clear. Further studies are necessary to confirm the durability
      of the strengthening effect and to exclude serious late complications. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 21183112
TI  - Posterior capsule management in congenital cataract surgery.
AB  - Management of the posterior capsule significantly affects the outcome of
      pediatric cataract surgery. Posterior capsule opacification (PCO) is rapid and
      virtually inevitable in very young children when adult-style cataract surgery is
      performed and the posterior capsule is left intact. In eyes with pediatric
      cataract, primary posterior capsulotomy and vitrectomy are considered routine
      surgical steps, especially in younger children. The site of intraocular lens
      (IOL) fixation and the surgical technique used also affect the prevalence of PCO.
      The present systematic review evaluates the options available to prevent PCO or
      ensure a clear central visual axis after pediatric cataract surgery. Newer
      approaches to posterior capsule management such as pars plicata posterior
      capsulorhexis, sutureless vitrectomy, sealed-capsule irrigation, and bag-in-the
      lens IOL are discussed. Management of the posterior capsule in the presence of a
      preexisting posterior capsule defect and posterior capsule plaque and options to
      treat PCO are also reviewed. FINANCIAL DISCLOSURE: No author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 21183113
TI  - Intraoperative complication during phacoemulsification in patient with
      epidermolysis bullosa.
AB  - We report the case of a 56-year-old woman with known recessive dystrophic
      epidermolysis bullosa and an unremarkable ocular history who experienced an
      extensive corneal epithelial blister during phacoemulsification cataract surgery.
      To our knowledge, this is the first report of this complication. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 21183114
TI  - Intrastromal corneal ring segments for bilateral keratoconus in an 11-year-old
      boy.
AB  - We present the case of an 11-year-old boy who had bilateral implantation of
      intrastromal corneal ring segments for progressive keratoconus and poor vision.
      No intraoperative or postoperative complications were seen, and 1 year
      postoperatively, the patient maintained good spectacle-corrected vision.
      FINANCIAL DISCLOSURE: Neither author has a financial or proprietary interest in
      any material or method mentioned.

PMID- 21183115
TI  - Haptic misfolding during aspheric IOL insertion.

PMID- 21183117
TI  - Consultation section. Refractive surgical problem.

PMID- 21183122
TI  - Appropriate time for assessing patient satisfaction with cataract surgery care.

PMID- 21183123
TI  - Relevance of aqueous humor concentrations of fluoroquinolones.

PMID- 21183125
TI  - Pediatric neuropharmacotherapeutics. Introduction.

PMID- 21183126
TI  - Developmental pharmacokinetics.
AB  - Physiological differences between children and adults result in age-related
      differences in pharmacokinetics and drug effect. In neonates and infants,
      decreased weight-adjusted doses are required because of decreased protein
      binding, renal excretion, and/or metabolism. For children older than 1 year of
      age, significantly higher weight-corrected doses compared with adults are needed
      for drugs eliminated by the cytochrome P450 (CYP) isozymes CYP1A2, CYP2C9, and
      CYP3A4. In contrast, weight-corrected doses for drugs eliminated by renal
      excretion or metabolism by CYP2C19, CYP2D6, N-Acetyl-transferase, and UDP
      glucuronosyltransferase in children are similar to those in adults. Ideally,
      pharmacokinetic and pharmacodynamic data should be available for all drugs used
      in children. Because many drugs are not approved for pediatric use, data are
      often limited, especially for older drugs. Understanding the effects of age on
      pharmacokinetics can help to determine appropriate pediatric dosing in situations
      in which there is limited information.

PMID- 21183127
TI  - New drugs for pediatric epilepsy.
AB  - The last 2 decades have witnessed an unprecedented period of new antiepileptic
      drug (AED) development. Newer-generation AEDs have been developed with the
      intention of improving the ease of use, decreasing drug interactions, decreasing
      adverse side effects, and identifying drugs with unique mechanisms of action,
      some of which may bear relevance to potential neuroprotective activity. Drug
      trials have also been refined in some cases to evaluate AED efficacy in children
      and against distinct epilepsy syndromes. This progress provides many new
      treatment options for the child neurologist facing children with epilepsy but
      also introduces the burden of determining appropriate AED choices. Here we
      highlight 6 new antiepileptic medications recently approved or pending approval
      for use in the United States: lacosamide, rufinamide, vigabatrin, retigabine,
      brivaracetam, and clobazam. For each of these medications, we present information
      regarding the history of drug development, proposed mechanism(s) of action,
      pharmacokinetics and recommended dosing, evidence for clinical efficacy,
      tolerability, and when, available, any unique features that are relevant for the
      pediatric population.

PMID- 21183128
TI  - Pediatric headache.
AB  - Headache is a common presenting complaint in the practice of child neurology. The
      medical and social impact of headache is often very severe both for the affected
      child and for his/her family. As there exist few good clinical studies to guide
      practitioners in choosing appropriate medications, treatments are mostly based on
      extrapolation of adult study results. Personal trial-and-error experience and
      specialized considerations for patients also influence choice and implementation.
      A careful medical history, however, can enable optimal choices for abortive and
      prophylactic use in the context of a multi-disciplinary approach toward headache
      management. This article provides a pathophysiologically-based overview of a wide
      range of therapeutic options for children and adolescents with headache.

PMID- 21183129
TI  - Advances in the treatment of attention-deficit/hyperactivity disorder: a guide
      for pediatric neurologists.
AB  - The purpose of this article is to assist pediatric neurologists in practice and
      in training to better understand and distinguish between several of the most
      commonly prescribed treatments for attention-deficit/hyperactivity disorder
      (ADHD) in school-aged children. Among the various pharmacotherapies available for
      ADHD, 4 specific medications will be reviewed: oral release osmotic system
      methylphenidate hydrochloride (CON; Concerta, McNeil Pharmaceuticals),
      lisdexamfetamine dimesylate (LDX; Vyvanse, Shire Pharmaceuticals), atomoxetine
      (ATX; Strattera, Eli Lilly), and guanfacine extended-release (GXR; Intuniv, Shire
      Pharmaceuticals). This article contains information including medication-release
      pattern, administration including available dosing, adverse reactions, and case
      studies to serve as a guide to help determine when a particular treatment might
      be more appropriate than another. Although ADHD is apparent across the lifespan,
      this article will focus on children with ADHD from ages 6 to 12 years old.
      Importantly, although a number of stimulant and nonstimulant treatment options
      are available for school-aged children diagnosed with ADHD, choosing the best
      treatment options is highly dependent on obtaining thorough family and medical
      histories.

PMID- 21183130
TI  - Pharmacology in childhood arterial ischemic stroke.
AB  - In recent years, there has been increasing recognition of the impact of childhood
      stroke and interest in the role of drugs in the acute, chronic, and prophylactic
      management of this condition. Most treatment strategies are based on studies in
      adults with stroke, and the relative infrequency of stroke and the heterogeneity
      of etiologies in childhood compared with adults present significant challenges in
      study design for childhood stroke studies. The presence of thrombophilia has been
      associated with stroke in children, strengthening the concept that
      antithrombotic, antiplatelet, and even thrombolytic agents have a role in stroke
      treatment and prevention. There are several potential roles for drugs in the
      treatment of childhood stroke including hyperacute therapy, antithrombotic
      medication, antiplatelet medication, and disease-specific medications. Herein, we
      review the use and rationale of these medications in childhood arterial ischemic
      stroke.

PMID- 21183131
TI  - Pharmacologic agents for pediatric neuroimmune disorders.
AB  - Autoimmune diseases make up a significant portion of the acute and chronic
      caseload of all pediatric neurologists. By comparing these diseases and their
      treatments side by side, common themes become evident. Therapeutic decisions
      follow patterns dependent on the clinical situation. Physicians must adapt
      therapy based on individual clinical responses. This article provides an overview
      of the current therapeutic options as they relate to the more common pediatric
      neuroimmune disorders.

PMID- 21183132
TI  - Pharmacotherapeutics of Tourette syndrome and stereotypies in autism.
AB  - Tourette syndrome (TS) and stereotypy in autism spectrum disorders (ASDs) are 2
      common movement disorders in childhood. The objective of this review was to
      summarize randomized controlled trials published over the past 5 years as an
      update of the current pharmacotherapeutic options for the treatment of tics, TS,
      and motor stereotypies in children with ASD. We searched MEDLINE (2005-May 2010)
      for randomized controlled trials of medications used for the treatment of these
      disorders. For the treatment of tics in TS, 2 trials suggest that levetiracetam
      is not effective, whereas 1 trial found that topiramate was effective. Single
      clinical trials of metoclopramide, atomoxetine, and ondansetron were of limited
      quality, preventing conclusions to be made regarding the usefulness of these
      treatments for tic disorders. For the treatment of stereotypy in children with
      ASD, risperidone has been shown in both a Cochrane review in 2006 and 2
      subsequent randomized control trials to be effective. The addition of
      pentoxifylline to risperidone may have added benefit. Haloperidol did not improve
      stereotypy and was poorly tolerated. There is good evidence that aripiprazole is
      effective in the treatment of sterotypies in children with ASD. A large
      randomized trial of citalopram did not show any improvement in stereotypy. Single
      trials of levetiracetam, guanfacine, and atomoxetine suggest they are not useful
      in the reduction of stereotypy in children with ASD.

PMID- 21183133
TI  - Pharmacologic treatment of spasticity in children.
AB  - Many clinicians frequently face the dilemma of whether and how to medically treat
      spasticity. When pharmacologic intervention is deemed appropriate, treatment
      decisions must first be based on accurate assessment using valid and reliable
      clinical instruments, and, importantly, specific, measurable, achievable, and
      realistic treatment goals should be delineated. For the treatment of localized or
      segmental spasticity, botulinum toxin (BoNT-A) is recommended as an effective and
      generally safe treatment. For more generalized spasticity, a number of useful
      oral agents and intrathecal baclofen are available, each with their positive and
      negative attributes. Fundamental knowledge of pharmacologic properties and
      toxicities of these medications is required for safe and appropriate use. To
      achieve optimum results, spasticity treatment should be part of an integrated
      therapeutic approach in which patients, caregivers, therapists, physicians, and
      surgeons have an open and clear communication about the overall rehabilitation
      process of the patient. This review summarizes the current pharmacologic
      approaches to spasticity treatment in children, critically evaluating published
      studies in the context of established evidence-based criteria.

PMID- 21183134
TI  - Treatment of acute pediatric pain.
AB  - Pediatric neurologists frequently treat acute pain in children. A broad range of
      medication options is available including nonsteroidal anti-inflammatory drugs,
      opioids, and other analgesic adjuvants, such as antidepressants and
      antiepileptics. This article reviews the physiology underlying the experience of
      pain and compares the pharmacologic mechanisms and properties of these
      medications, providing a framework for developing effective multimodal medical
      treatment approaches to pain in children.

PMID- 21183135
TI  - Infant fatality.

PMID- 21183138
TI  - A vaccine against meningitis in Africa.

PMID- 21183139
TI  - Promising control of genital warts: but is elimination possible?

PMID- 21183140
TI  - Fighting bacterial resistance at the root: need for adapted EMEA guidelines.

PMID- 21183141
TI  - Surveillance, characterisation, and preservation of multidrug-resistant bacteria.

PMID- 21183143
TI  - Role of multidrug-resistant pathogens in health-care-associated pneumonia.

PMID- 21183145
TI  - Prescription of antibiotics in hospitals: prescribers' opinions matter.

PMID- 21183146
TI  - Obesity-related immunodeficiency in patients with pandemic influenza H1N1.

PMID- 21183148
TI  - Endotoxin removal devices for the treatment of sepsis and septic shock.
AB  - A substantial body of experimental and clinical evidence suggests that
      neutralising or removing lipopolysaccharide endotoxin would be an effective
      adjunctive approach to the management of Gram-negative sepsis. Polymyxins are a
      group of cyclic cationic polypeptide antibiotics. Although they have useful
      antimicrobial activity against Gram-negative bacteria, their clinical use has
      been limited because of toxicity. However, in addition to their antimicrobial
      property, polymyxins can bind to and neutralise endotoxin. Thus, investigators
      have explored the possibility of using polymyxin bound to a solid-phase carrier
      for specific haem-adsorption in patients with sepsis, thereby retaining the
      lipopolysaccharide-binding properties but minimising systemic toxic effects. This
      system has been widely used in Japan for many years, but convincing clinical
      evidence of efficacy is lacking. A recent Italian study has some promising data.
      Although polymyxin has been the principal agent used to explore this approach,
      other molecules have the ability to bind endotoxin, and some of these have very
      recently been proposed as the basis for other endotoxin-removal devices. The
      available evidence is reviewed to assess the potential use of such devices in
      clinical practice.

PMID- 21183147
TI  - Antimalarial drug resistance of Plasmodium falciparum in India: changes over time
      and space.
AB  - After the launch of the National Malaria Control Programme in 1953, the number of
      malaria cases reported in India fell to an all-time low of 0.1 million in 1965.
      However, the initial success could not be maintained and a resurgence of malaria
      began in the late 1960s. Resistance of Plasmodium falciparum to chloroquine was
      first reported in 1973 and increases in antimalarial resistance, along with rapid
      urbanisation and labour migration, complicated the challenge that India's large
      geographical area and population size already pose for malaria control. Although
      several institutions have done drug-resistance monitoring in India, a complete
      analysis of countrywide data across institutions does not exist. We did a
      systematic review of P falciparum malaria drug-efficacy studies in India to
      summarise drug-resistance data and describe changes over the past 30 years to
      inform future policy. Continued use of chloroquine for treatment of P falciparum
      malaria in India will likely be ineffective. Resistance to sulfa-pyrimethamine
      should be closely monitored to protect the effectiveness of treatment with
      artesunate plus sulfadoxine-pyrimethamine, which is the new first-line treatment
      for P falciparum malaria. Strategies to reduce the emergence and spread of future
      drug resistance need to be proactive and supported by intensive monitoring.

PMID- 21183149
TI  - Hunting Sarcoptes scabiei-dead or alive!

PMID- 21183150
TI  - Third- and fourth-degree perineal tears: prevalence and risk factors in the third
      millennium.
AB  - OBJECTIVE: We sought to assess the modern prevalence and risk factors for third-
      and fourth-degree perineal tears. STUDY DESIGN: The study population comprised
      38,252 women who delivered in one medical center, from January 2005 through
      December 2009, and met the following inclusion criteria: singleton pregnancy,
      vertex presentation, and vaginal delivery. Of these, 96 women (0.25%) sustained
      third- or fourth-degree perineal tears. Maternal and obstetric variables were
      compared between women with vs without severe perineal tears. RESULTS: Five
      variables were found to be statistically significant independent risk factors:
      Asian ethnicity (odds ratio [OR], 8.9; 95% confidence interval [CI], 4.2-18.9),
      primiparity (OR, 2.4; 95% CI, 1.5-3.7), persistent occipito posterior (OR, 2.1;
      95% CI, 1-4.5), vacuum delivery (OR, 2.7; 95% CI, 1.6-4.6), and heavier
      birthweight (OR, 1.001; 95% CI, 1-1.001). CONCLUSION: Severe perineal tears are
      uncommon in modern obstetric practice. Significant risk factors are Asian
      ethnicity, primiparity, persistent occipito posterior, vacuum delivery, and
      heavier birthweight.

PMID- 21183152
TI  - Managing disruptive behaviors in the health care setting: focus on obstetrics
      services.
AB  - Disruptive behaviors can have a significant negative impact on staff
      relationships, communication flow, task responsibility, and team collaboration,
      all of which can adversely impact patient outcomes of care. Addressing disruptive
      behaviors in a positive manner by emphasizing the benefits of mutual
      understanding, shared goals and priorities, and adherence to accepted standards
      of care will enhance communication flow and improve the process and outcomes of
      care. This is particularly relevant in the obstetrics setting, where care is
      delivered over a continuum of time, with multiple different members of the health
      care team playing a vital role as the patient progresses from labor to delivery.
      Critical strategies for success include having strong organizational commitment
      and leadership support, raising provider insight and awareness, implementing
      appropriate policies and procedures, providing appropriate educational and
      training programs, and facilitating action-oriented interventional support.

PMID- 21183151
TI  - General maternal medication use, folic acid, the MDR1 C3435T polymorphism, and
      the risk of a child with a congenital heart defect.
AB  - OBJECTIVE: We sought to investigate maternal and child functional MDR1 C3435T
      polymorphism, periconception medication, folic acid use, and the risk of a
      congenital heart defect (CHD) in the offspring. STUDY DESIGN: MDR1 3435C>T
      genotyping was performed in 283 case triads (mother, father, child) and 308
      control triads. Information on periconception medication and folic acid use was
      obtained through questionnaires. RESULTS: Mothers with MDR1 3435CT/TT genotype
      and using medication showed a significant association with the risk of a child
      with CHD (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.3-4.3) compared
      to mothers with MDR1 3435CC genotype not using medication. This risk increased
      without folic acid use (OR, 2.8; 95% CI, 1.2-6.4), and decreased in folic acid
      users (OR, 1.7; 95% CI, 0.8-3.7). Children carrying the MDR1 3435CT/TT genotype
      and periconceptionally exposed to medication without folic acid did not show
      significant risks. CONCLUSION: Mothers carrying the MDR1 3435T allele, using
      medication without folic acid, are at nearly 3-fold increased risk for CHD in the
      offspring.

PMID- 21183153
TI  - Gestational hypertension: a neglected cardiovascular disease risk marker.
AB  - OBJECTIVE: The purpose of this study is to examine hypertension and cholesterol
      screening, knowledge of heart attack symptoms, and cardiovascular disease (CVD)
      risk factors among women with a history of gestational hypertension. STUDY
      DESIGN: We used weighted 2008 National Health Interview Survey data to examine
      health indicators and modifiable CVD risk factors and to estimate prevalence and
      adjusted odds ratios for recommended CVD screening and knowledge of heart attack
      symptoms by hypertension history among 11,970 adult women. RESULTS: Among women
      with gestational hypertension only (n = 301), 93% received the recommended
      screening for hypertension; 75% received screening for dyslipidemia, and 40%
      correctly identified 5 of 5 heart attack symptoms. The odds of CVD screenings and
      knowledge did not differ between women with a history of gestational hypertension
      and those with no hypertension. However, women with gestational hypertension had
      higher rates of obesity (43%), CVD (18%), and diabetes mellitus (13%), compared
      with women without a history of hypertension (21%, 8%, and 3%, respectively).
      CONCLUSION: A history of gestational hypertension is a neglected CVD risk marker.

PMID- 21183154
TI  - Midtrimester bacterial vaginosis and cervical length in women at risk for preterm
      birth.
AB  - OBJECTIVE: The purpose of this study was to estimate the effect of bacterial
      vaginosis on midtrimester cervical length in women at increased risk for
      recurrent spontaneous preterm birth. STUDY DESIGN: We conducted a secondary
      analysis of prerandomization data from a multicenter trial of ultrasound
      indicated cerclage. Women with previous spontaneous preterm birth at <34 weeks'
      gestation underwent initial cervical length assessment and vaginal fluid
      collection at 16-21 weeks 6 days gestation. Gram stains were scored with Nugent
      criteria. With serial scans, the shortest cervical length was observed. RESULTS:
      Records for 949 women had complete data. In unadjusted regression models, Nugent
      score (P = .003) and vaginal fluid pH (P = .008) were related inversely to
      cervical length. Women with bacterial vaginosis based on Nugent score >=7 (P =
      .04) or pH >=5 (P = .016) had significantly lower cervical length than unaffected
      women; however, all of these effects were null after covariate adjustment.
      CONCLUSION: Nugent score, pH level, and bacterial vaginosis are associated
      inversely with cervical length; however, these relationships become null after
      adjustment for relevant covariates.

PMID- 21183155
TI  - Comparison of biomechanical loading during use of conventional stud welding
      equipment and an alternate system.
AB  - We investigated the effect of an alternative welding system designed to reduce
      exposure to extreme trunk flexion on measures of trunk inclination and muscle
      activity. Among 10 participants, data were collected while using conventional
      stud welding equipment and while using the alternate system. Paired t-tests were
      used to compare results between the two welding systems. Mean trunk inclination
      angle was reduced with the alternate system (34.4 degrees  versus 9.7 degrees , p
      < 0.01). Percent time with trunk inclination angles greater than 60 degrees  was
      also reduced (40.0% versus 4.7%, p < 0.01). In general, the alternate system
      resulted in less desirable upper trapezius muscle activity levels. The alternate
      system appears to be effective in reducing exposure to extreme trunk flexion
      among stud welders. Continued development of the system should explore features
      designed to reduce shoulder forces and improve productivity.

PMID- 21183156
TI  - Interactive effects of acute experimental pain in trapezius and sored wrist
      extensor on the electromyography of the forearm muscles during computer work.
AB  - We investigated the interactive effects of shoulder pain and wrist extensor
      muscle soreness on surface electromyography (EMG) during computer mouse work. On
      day one, subjects (N = 12) performed computer work with/without acute muscle pain
      induced in the trapezius muscle. Subsequently, eccentric exercise was performed
      to induce delayed onset muscle soreness (DOMS) in wrist extensor muscles. In
      presence of DOMS on day two, computer work recordings with/without pain were
      repeated. EMG signals were recorded from the descending part of trapezius
      bilaterally, flexor carpi ulnaris and extensor carpi radialis brevis.
      Experimental muscle pain in trapezius led to a decrease in the muscular activity
      of the wrist extensor (P < 0.02) and decreased the relative rest time in the
      wrist flexor even in presence of DOMS (P < 0.01). The present result suggests
      that shoulder pain plays a role in the coordination of wrist flexors and
      extensors during computer work.

PMID- 21183157
TI  - Prevalence and antifungal resistance profile of Candida spp. oral isolates from
      patients with type 1 and 2 diabetes mellitus.
AB  - OBJECTIVE: The goal of the study was to measure the prevalence of Candida spp. in
      the oral cavity of patients with diabetes types 1 and 2 when compared to healthy
      individuals and to study antifungal resistance profile of the isolates. DESIGN:
      There were 162 subjects in the study: diabetes type 1 (n=39); control group 1
      (n=50): healthy individuals matched in gender, age, and oral conditions to
      diabetes type 1 patients; diabetes type 2 (n=37); control group 2 (n=36) who were
      matched to each patient of the diabetes type 2 group. Stimulated saliva was
      collected and isolates were identified with phenotypic tests. The presence of C.
      dubliniensis was determined by multiplex PCR. RESULTS: There were no
      statistically significant differences in Candida spp. frequency between the
      diabetes 1 group and its control (p=0.443) nor between the diabetes 2 group and
      its control (p=0.429). C. albicans was the most frequently isolated yeast in all
      groups. In the diabetes groups, C. stellatoidea, C. parapsilosis, C. tropicalis,
      C. lipolytica, C. glabrata, and C. krusei were also identified. Additionally, in
      control groups, C. kefyr was also detected. None of the isolates were resistant
      to amphotericin B and flucytosine. A low percentage of the isolates were
      resistant to ketoconazole. CONCLUSIONS: No differences were detected in
      colonization of Candida spp. oral isolates from type 1 and type 2 diabetes when
      compared to matched controls. The antifungal resistance of Candida spp. isolates
      for ketoconazole from type 1 diabetes patients was significantly higher than that
      of its matched control.

PMID- 21183158
TI  - Anterior cingulate activation is related to a positivity bias and emotional
      stability in successful aging.
AB  - BACKGROUND: Behavioral studies consistently reported an increased preference for
      positive experiences in older adults. The socio-emotional selectivity theory
      explains this positivity effect with a motivated goal shift in emotion
      regulation, which probably depends on available cognitive resources. The present
      study investigates the neurobiological mechanism underlying this hypothesis.
      METHODS: Functional magnetic resonance imaging data were acquired in 21 older and
      22 young subjects while performing a spatial-cueing paradigm that manipulates
      attentional load on emotional face distracters. We focused our analyses on the
      anterior cingulate cortex as a key structure of cognitive control of emotion.
      RESULTS: Elderly subjects showed a specifically increased distractibility by
      happy faces when more attentional resources were available for face processing.
      This effect was paralleled by an increased engagement of the rostral anterior
      cingulate cortex, and this frontal engagement was significantly correlated with
      emotional stability. CONCLUSIONS: The current study highlights how the brain
      might mediate the tendency to preferentially engage in positive information
      processing in healthy aging. The finding of a resource-dependency of this
      positivity effect suggests demanding self-regulating processes that are related
      to emotional well-being. These findings are of particular relevance regarding
      implications for the understanding, treatment, and prevention of nonsuccessful
      aging like highly prevalent late-life depression.

PMID- 21183159
TI  - Interaction of 5-HTTLPR and a variation on the oxytocin receptor gene influences
      negative emotionality.
AB  - BACKGROUND: Pharmacological studies indicate a functional interaction between the
      serotonergic and oxytocinergic system. METHODS: This study tested for an
      interaction of the prominent serotonin transporter polymorphism (SLC6A4) and an
      oxytocin receptor gene variation on individual differences in negative
      emotionality in healthy Caucasians (n = 750). RESULTS: Participants carrying both
      the homozygous LL-variant of the serotonin transporter polymorphism and the TT
      variant of the single nucleotide polymorphism rs2268498 on the oxytocin receptor
      gene showed lowest scores on the personality dimensions Fear and Sadness of the
      Affective Neuroscience Personality Scales, as well as on an underlying factor
      Negative Emotionality. CONCLUSIONS: The observed interaction effect provides
      converging evidence from human molecular genetics that serotonergic and
      oxytocinergic neurotransmission are entwined and play a crucial role for human
      personality with implications for affective disorders.

PMID- 21183162
TI  - Full disclosure in industry-sponsored laboratory medicine research studies:
      Statement by the Consortium of Laboratory Medicine Journal Editors.

PMID- 21183163
TI  - A multi-stage automatic arrhythmia recognition and classification system.
AB  - This paper describes an automatic classification system based on combination of
      diverse features for the purpose of automatic heartbeat recognition. The method
      consists of three stages. At the first stage, heartbeats are classified into 5
      main groups defined by AAMI using optimal feature sets for each main group. At
      the second stage, main groups are classified into subgroups using optimal
      features for each subgroup. Then the third stage is added to the system for
      classifying beats that are labeled as unclassified beats in the first two
      classification stages. A diverse set of features including higher order
      statistics, morphological features, Fourier transform coefficients, and higher
      order statistics of the wavelet package coefficients are extracted for each
      different type of ECG beat. At the first stage, optimal features for main groups
      are determined by using a wrapper type feature selection algorithm. At the second
      stage, optimal features are similarly selected for discriminating each subgroup
      of the main groups. Then at the third stage, only raw data is used for
      classifying beats. In all stages, the classifiers are based on the k-nearest
      neighbor algorithm. ECG records used in this study are obtained from the MIT-BIH
      arrhythmia database. The classification accuracy of the proposed system is
      measured by sensitivity, selectivity, and specificity measures. The system is
      classified 16 heartbeat types. The measures of proposed system are 85.59%,
      95.46%, and 99.56%, for average sensitivity, average selectivity, and average
      specificity, respectively.

PMID- 21183160
TI  - Gray matter alterations in adults with attention-deficit/hyperactivity disorder
      identified by voxel based morphometry.
AB  - BACKGROUND: Gray and white matter volume deficits have been reported in many
      structural magnetic resonance imaging (MRI) studies of children with attention
      deficit/hyperactivity disorder (ADHD); however, there is a paucity of structural
      MRI studies of adults with ADHD. This study used voxel based morphometry and
      applied an a priori region of interest approach based on our previous work, as
      well as from well-developed neuroanatomical theories of ADHD. METHODS: Seventy
      four adults with DSM-IV ADHD and 54 healthy control subjects comparable on age,
      sex, race, handedness, IQ, reading achievement, frequency of learning
      disabilities, and whole brain volume had an MRI on a 1.5T Siemens scanner. A
      priori region of interest hypotheses focused on reduced volumes in ADHD in
      dorsolateral prefrontal cortex, anterior cingulate cortex, caudate, putamen,
      inferior parietal lobule, and cerebellum. Analyses were carried out by FSL-VBM
      1.1. RESULTS: Relative to control subjects, ADHD adults had significantly smaller
      gray matter volumes in parts of six of these regions at p <= .01, whereas parts
      of the dorsolateral prefrontal cortex and inferior parietal lobule were
      significantly larger in ADHD at this threshold. However, a number of other
      regions were smaller and larger in ADHD (especially fronto-orbital cortex) at
      this threshold. Only the caudate remained significantly smaller at the family
      wise error rate. CONCLUSIONS: Adults with ADHD have subtle volume reductions in
      the caudate and possibly other brain regions involved in attention and executive
      control supporting frontostriatal models of ADHD. Modest group brain volume
      differences are discussed in the context of the nature of the samples studied and
      voxel based morphometry methodology.

PMID- 21183164
TI  - Effects of HUD-supported lead hazard control interventions in housing on
      children's blood lead.
AB  - The Evaluation of the US Department of Housing and Urban Development Lead-Based
      Paint Hazard Control Grant Program studied the effectiveness of the housing
      intervention performed in reducing the blood lead of children at four post
      intervention times (6-months, 1-year, 2-years, and 3-years). A repeat measures
      analysis showed that blood lead levels declined up to three-years post
      intervention. The results at each successive collection time were significantly
      lower than at the previous post-intervention time except for the difference
      between the levels at two and three years. At two-years post-intervention,
      geometric mean blood lead levels were approximately 37% lower than at pre
      intervention. Children with pre-intervention blood lead levels as low as 10
      MUg/dL experienced substantial declines in blood lead levels. Previous studies
      have found substantial improvements only if a child's pre-intervention blood lead
      level was above 20 MUg/dL. Individual interior lead hazard control treatments as
      grouped by Interior Strategy were not a significant predictor of post
      intervention blood lead levels. However, children living in dwellings where
      exterior lead hazard control interventions were done had lower blood lead levels
      at one-year post-intervention than those living in dwellings without the exterior
      interventions (all other factors being equal), but those differences were only
      significant when the mean exterior paint lead loading at pre-intervention was
      about the 90th percentile (7.0mg/cm(2)). This observation suggests that exterior
      lead hazard control can be an important component of a lead hazard control plan.
      Children who were six to eleven months of age at pre-intervention had a
      significant increase in blood lead at one-year post-intervention, probably due to
      other exposures.

PMID- 21183165
TI  - [Consequences of lawsuits on affected doctors].
AB  - OBJECTIVES: To determine the consequences of a judicial claim on the private life
      and professional practice of affected doctors. MATERIAL AND METHODS: A cross
      sectional, descriptive study was performed on the basis of 169 surveys filled out
      by physicians subjected to a lawsuit in Spain in the period including 2002-2005.
      RESULTS: The claim produced a bad or very bad personal experience in 98.8%. A
      total of 85.1% admitted repercussions on family life, 84% made some change in the
      way they worked, and 57.4% admitted effects on their vocation. There was an
      unfavorable court ruling in 6%. CONCLUSIONS: There were important repercussions
      on doctors after a lawsuit, both on their private and family life, as well as the
      way they approach medical practice.

PMID- 21183166
TI  - [Hepatic glycogenosis in a patient with type 1 diabetes mellitus].

PMID- 21183167
TI  - [Toxicity and causes of change of antiretroviral regimen among immigrant patients
      with HIV infection].

PMID- 21183168
TI  - [Lanthanum carbonate: a novel explanation of a common x-ray image].

PMID- 21183169
TI  - Antral follicle count in clinical practice: building the bridge from ovarian
      reserve to in vitro fertilization outcome.
AB  - Antral follicle count provides a useful assessment of ovarian reserve to predict
      ovarian response, estimate risk for cycle cancellation, optimize stimulation
      protocol selection, and confidently select suitable candidates for IVF.

PMID- 21183170
TI  - The role of varicocele repair in nonobstructive azoospermia must be evaluated
      with controlled trials rather than observational studies.
AB  - Certainly, varicoceles can have a substantive effect on sperm production in
      infertile males. In addition, varicocele repair may optimize sperm production.
      However, additional studies and evaluation of the role of varicocele repair in
      men with this condition (nonobstructive azoospermia) are warranted.

PMID- 21183171
TI  - A subserosal uterus-like mass presenting after a sliding hernia of the ovary and
      endometriosis: a rare entity with a discussion of the histogenesis.
AB  - OBJECTIVE: To report the first case of a subserosal uterus-like mass. DESIGN:
      Case report. SETTING: A community-based hospital. PATIENT(S): A 44-year-old
      nulliparous woman who complained of a left inguinal mass had a medical history
      that was notable for two features. One was left oophorectomy for a sliding hernia
      at 10 months of age; the other was endometriosis at the oophorectomy site at 26
      years of age. INTERVENTION(S): Tumorectomy. MAIN OUTCOME MEASURE(S): Not
      applicable. RESULT(S): Pathologic examination demonstrated that this subserosal
      mass mimicked a miniature uterus with a leiomyomatous lesion. CONCLUSION(S): As
      of September 2010, 23 cases of uterus-like mass had been reported. Three
      pathologic theories of uterus-like mass have been proposed: [1] congenital
      anomaly theory, [2] metaplasia theory, and [3] heterotopia. The pathogenesis of
      this rare entity is currently under debate. Most uterus-like masses have been
      connected to the genital organs (75.0%) and associated with endometriosis
      (50.0%). In the present case, the uterus-like mass developed at the surgical scar
      site of oophorectomy for a sliding hernia and a tumorectomy for endometriosis. We
      review the literature and discuss the theories regarding the histogenesis of
      uterus-like mass.

PMID- 21183173
TI  - A rational approach to the management of varicocele-associated nonobstructive
      azoospermia.
AB  - A consensus needs to be reached on a rational approach to infertile men with
      varicocele-associated nonobstructive azoospermia. Future studies are warranted to
      understand the mechanism behind the variable influence of varicocele on
      testicular function, which causes partial or complete damage of spermatogenesis
      in some cases and leaves it unaltered in others.

PMID- 21183174
TI  - Do oocyte quality and quantity as measured by antral follicle count decline in
      parallel?
AB  - It is clear that with chronological aging both oocyte quantity (ultimately
      leading to menopause) and quality (pregnancy potential) decline. It is less
      clear, however, whether these three parameters: chronological age, oocyte number,
      and oocyte "health," decline in parallel.

PMID- 21183175
TI  - Miscarriage karyotype and its relationship with maternal body mass index, age,
      and mode of conception.
AB  - This study investigated the association between miscarriage karyotype and body
      mass index, maternal age, and mode of conception. Miscarriages after IVF and/or
      intracytoplasmic sperm injection were less frequently aneuploid; advanced
      maternal age was associated with an increase in aneuploid products of conception;
      overweight and obese women aged <35 years were less likely to have aneuploid
      miscarriages than women in a healthy weight range, suggesting alternate
      mechanisms for miscarriage in this population.

PMID- 21183176
TI  - Diagnostic testicular biopsy before varicocele repair plays a realistic and
      important role.
AB  - We believe that diagnostic testicular biopsy before varicocele repair is
      important, despite the risks.

PMID- 21183177
TI  - Cervical endometriosis associated with malignant pleural mesothelioma mimicking
      cervical cancer--Occam's razor or the "third man".
AB  - OBJECTIVE: To illustrate pitfalls in the diagnosis of endometriosis and cervical
      cancer. DESIGN: Case report. SETTING: University hospital, department of
      obstetrics and gynecology. PATIENT(S): A 45-year-old woman with menorrhagia,
      pelvic mass, right-sided hydronephrosis, and unexplained weight loss.
      INTERVENTION(S): Cervical biopsies were suggestive of cervical endometriosis.
      Laparoscopy confirmed endometriosis. Associated pleural effusion, without
      cytologic signs of malignancy, was interpreted as caused by thoracic
      endometriosis. The patient had a transabdominal hysterectomy and unilateral
      salpingo-oophorectomy. Histopathologic examination confirmed endometriosis and
      revealed a residual tubo-ovarian abscess. After surgery, the patient developed
      spontaneous seropneumothorax. Pleural biopsies revealed a well-differentiated
      epithelial malignant pleural mesothelioma. The patient underwent hypofractionated
      radiation of drain sites. She is now observed in our outpatient clinic. MAIN
      OUTCOME MEASURE(S): Steps to the correct diagnosis. RESULT(S): The patient had an
      association of cervical and pelvic endometriosis, residual tubo-ovarian abscess,
      and malignant pleural mesothelioma. CONCLUSION(S): Usually, the simplest
      diagnosis explaining a complex of symptoms and clinical and diagnostic findings
      is the one most likely to be correct. This is an application of Occam's razor to
      medicine. Our case illustrates that occasionally the simplest and therefore most
      probable diagnosis can be wrong, and on these occasions one should consider a
      "third man."

PMID- 21183178
TI  - Other work has highlighted the limitations of using histopathology to predict
      success after varicocelectomy.
AB  - The morbidity associated with performing testicular biopsy on all men before
      varicocele repair appears to outweigh the benefit of any prognostic information
      obtained.

PMID- 21183179
TI  - Smart Self-Assembling MagnetS for ENdoscopy (SAMSEN) for transoral endoscopic
      creation of immediate gastrojejunostomy (with video).
AB  - BACKGROUND: Gastrojejunostomy is important for palliation of malignant gastric
      outlet obstruction and surgical obesity procedures. A less-invasive endoscopic
      technique for gastrojejunostomy creation is conceptually attractive. Our group
      has developed a compression anastomosis technology based on endoscopically
      delivered self-assembling magnets for endoscopy (SAMSEN) to create an instant,
      large-caliber gastrojejunostomy. OBJECTIVE: To develop and evaluate an endoscopic
      means of gastrojejunostomy creation by using SAMSEN. SETTING: Developmental
      laboratory and animal facility. DESIGN: Animal study and human cadaveric study.
      SUBJECTS: Yorkshire pigs (7 cadaver, 5 acute); human (1 cadaver). INTERVENTIONS:
      A transoral procedure for SAMSEN delivery was developed in porcine and human
      cadaver models. Subsequently, gastrojejunostomy creation by using SAMSEN was
      performed in 5 acute pigs. The endoscope was advanced into the peritoneal cavity
      through the gastrotomy, and a segment of the small bowel was grasped and pulled
      closer to the stomach. An enterotomy was created, and a custom overtube was
      advanced into the small bowel for deployment of the first magnetic assembly.
      Next, a reciprocal magnetic assembly was deployed in the stomach. The 2 magnetic
      systems were mated under fluoroscopic and endoscopic guidance. Contrast studies
      assessed for gastrojejunostomy leak. Immediate necropsies were performed. MAIN
      OUTCOME MEASUREMENTS: Technical feasibility and complications. RESULTS:
      Gastrojejunostomy creation by using SAMSEN was successful in all 5 animals. Deep
      enteroscopy was performed through the stoma without difficulty. No leaks were
      identified on contrast evaluation. At necropsy, the magnets were properly
      deployed and robustly coupled together, resistant to vigorous tissue
      manipulation. LIMITATIONS: Acute animal study. CONCLUSIONS: Endoscopic creation
      of immediate gastrojejunostomy by using SAMSEN is technically feasible.

PMID- 21183180
TI  - Projected incidence of proximal femoral fracture in England: a report from the
      NHS Hip Fracture Anaesthesia Network (HIPFAN).
AB  - AIMS: This study was designed to estimate trends in the number of proximal
      femoral fractures (PFFs), and consequent bed day requirements and financial
      implications for England until 2033. METHODS: Trends in the number of coded PFFs
      from 1998 to 2008 (collected from Hospital Episode Statistics Online) were
      projected forward to 2033, and modified according to published data concerning
      population demographics and declining PFF prevalence. Estimates of 30 day
      postoperative mortality were calculated according to projected demographic data.
      Financial estimates were calculated according to current cost and adjusted
      according to projected inflation. RESULTS: Despite a decline in the prevalence of
      PFF among the aging population (2.98% since 2002), we estimate that approximately
      100,000 patients annually will require surgery for fractured neck of femur by
      2033 in England, with a 30d mortality of 8.9-9.3%, costing L3.6-5.6 billion
      (inflation adjusted) in total care. CONCLUSIONS: The evaluation and
      implementation of cost-effective preventive and therapeutic strategies in the
      short term may help to ameliorate the future financial burden of PFF, and, more
      importantly, improve the outcome and quality of life for the elderly after
      fracture.

PMID- 21183181
TI  - Ivabradine improves coronary flow reserve in patients with stable coronary artery
      disease.
AB  - OBJECTIVES: Although treatment with ivabradine reduces the incidence of hospital
      admissions for myocardial infarction and coronary revascularisation, there are no
      data concerning its effect on coronary circulation. The purpose of this study was
      to assess the effects of ivabradine on coronary flow velocity and flow reserve
      (CFR) in patients with stable coronary artery disease (CAD). METHODS: During
      diagnostic coronary angiography (baseline), twenty-one patients with stable CAD
      underwent coronary flow velocity measurements (APV cm/s) in a non-culprit vessel,
      using a Doppler guidewire, at rest (r) and after adenosine administration to
      achieve maximal hyperaemia (h). During programmed coronary intervention in the
      culprit vessel, the same measurements were repeated one week after treatment with
      ivabradine (5 mg twice daily), both at the intrinsic heart rate and at a paced
      heart rate identical to that before treatment. CFR was defined as h-APV/r-APV.
      RESULTS: Heart rate was significantly lower after treatment with ivabradine (78+/
      14 bpm vs 65+/-9 bpm, p<0.001). Also, a reduction of r-APV (17.0+/-5.5 vs 19.7+/
      7.6, p=0.003) and augmentation of h-APV (57.9+/-17.8 vs 53.5+/-21.4, p=0.009)
      leading to CFR improvement (3.51+/-0.81 vs 2.78+/-0.61, p<0.001) were observed.
      During pacing, although r-APV reverted to values similar to those before
      treatment (20.0+/-6.5 vs 19.7+/-7.6, p=NS), a sustained improvement in h-APV was
      observed (59.5+/-19.7 vs 53.5+/-21.4, p=0.007) and CFR remained higher than
      before treatment (3.04+/-0.66 vs 2.78+/-0.61, p<0.001). CONCLUSIONS: Ivabradine
      treatment significantly improves hyperaemic coronary flow velocity and CFR in
      patients with stable CAD. These effects remain even after heart rate correction
      indicating improved microvascular function.

PMID- 21183182
TI  - Eosinophil cationic protein and clinical outcome after bare metal stent
      implantation.
AB  - OBJECTIVE: we assessed the association between baseline eosinophil cationic
      protein (ECP) levels, a sensitive marker of eosinophil activation, and clinical
      outcome in patients undergoing bare metal stent (BMS) implantation. METHODS:
      basal ECP levels were measured in 110 patients (69+/-11 years, 88 men) undergoing
      BMS implantation. Major adverse cardiac events (MACEs), defined as cardiac death,
      non-fatal myocardial infarction, or clinically-driven target lesion
      revascularization, were registered at 24-month follow-up. RESULTS: eighteen
      (16.4%) patients had MACEs and showed higher ECP levels compared with those
      without MACEs [20.1 (9.8-47.3) vs. 9.5 (5.0-27.2) g/L, p=0.02]. At follow-up, ECP
      level>11 g/L was the only significant predictor of MACEs (HR 3.5, 95% CI 1.1
      10.4, p=0.03). CONCLUSION: basal ECP levels are associated with MACEs after BMS
      implantation, suggesting that an allergic-mediated inflammation against the metal
      could explain some adverse reactions occurring after coronary stenting.

PMID- 21183183
TI  - High circulating levels of large splice variants of tenascin-C is associated with
      mortality and cardiovascular disease in chronic kidney disease patients.
AB  - OBJECTIVES: Tenascin-C (TN-C) is an adhesion-modulating extracellular matrix
      glycoprotein which is overexpressed in various organs under disease conditions
      (infection and inflammation). In patients with heart disease, plasma TN-C levels
      have been shown to be predictive of cardiac remodeling. Chronic kidney disease
      (CKD) is associated with a state of chronic inflammation and high cardiovascular
      morbidity and mortality. METHODS: In a prospective observational study, we
      examined the relationship between plasma concentration of large splice variants
      of TN-C (cTN-C) and cardiovascular outcomes, we studied a cohort of 94 prevalent
      CKD patients (mean+/-SD age: 68+/-13; 31% at CKD stages 2-3, 31% at stages 4-5,
      38% at stage 5D). RESULTS: Plasma cTN-C levels were elevated in this population
      and tended to rise as CKD progressed, with the increase becoming statistically
      significant at CKD stage 4-5 and 5D. Multivariate linear regression analysis
      indicated that CKD stage (p=0.04), IL-6 (p=0.02) and albumin (p=0.02) were
      independently associated with plasma cTN-C levels. During follow-up (mean
      duration: 969+/-405 days), 32 patients died (19 from CV events, 7 from infectious
      diseases and 6 from other causes). In a crude analysis, higher plasma cTN-C
      levels predicted overall and CV mortality (p=0.007 and p=0.003, respectively) and
      were associated with higher occurrence of CV events. Cox analyses confirmed that
      elevated plasma cTN-C levels were independently associated with cardiovascular
      events, cardiovascular and overall mortality. CONCLUSION: Our findings suggest,
      for the first time, that plasma cTN-C levels are independently associated with
      cardiovascular outcomes in CKD patients. Further studies are needed in order to
      confirm the above observations and better understand TN-C's role in
      cardiovascular remodeling in CKD.

PMID- 21183184
TI  - The start-to-end chemometric image processing of 2D thin-layer videoscans.
AB  - The purpose of the research was to recommend a unified procedure of image
      preprocessing of 2D thin layer videoscans for further supervised or unsupervised
      chemometric analysis. All work was done with open source software. The videoscans
      saved as JPG files underwent the following procedures: denoising using a median
      filter, baseline removal with the rollerball algorithm and nonlinear warping
      using spline functions. The application of the proposed procedure enabled
      filtration of random difference between images (background intensity changes and
      spatial differences of the spots location). After the preprocessing only spot
      intensities have an influence on the performed PCA or other techniques. The
      proposed technique was successfully applied to recognize the differences between
      three Carex species from the 2D videoscans of the extracts. The proposed solution
      may be of value for the any chemometric task--both unsupervised and supervised.

PMID- 21183185
TI  - Dissociation and fractionation of heavy and light chains from IgG monoclonal
      antibodies.
AB  - A basic method for dissociation and fractionation of monoclonal IgG heavy and
      light chain is described. It employs less noxious and hazardous reagents than the
      classical mercaptoethanol/propionic acid process and replaces size exclusion
      chromatography with cation exchange on a monolith to improve productivity.
      Significant scope remains to refine the conditions. The method can be applied to
      other disulfide bonded proteins with significant affinity for cation exchangers.

PMID- 21183186
TI  - Analysis of UV ink photoinitiators in packaged food by fast liquid chromatography
      at sub-ambient temperature coupled to tandem mass spectrometry.
AB  - A fast method of liquid chromatography coupled to tandem mass spectrometry (LC
      MS/MS) was developed for the analysis of eleven UV ink photoinitiators in
      packaged food. Chromatographic separation was achieved in a
      pentafluorophenylpropyl (PFPP) column at 5 degrees C and acetonitrile:25 mM
      formic acid-ammonium formate (pH 2.7) in gradient elution. To reduce sample
      treatment, a QuEChERS (quick, easy, cheap, effective, rugged and safe) method for
      the extraction and clean-up of UV photoinitiators in packaged foods was
      evaluated. Triple quadrupole working in H-SRM on Q1 mode was used for both
      quantitation and confirmation purposes and the most intense and selective
      transitions were chosen. Quality parameters of the developed QuEChERS LC-MS/MS
      method were established and applied for the analysis of photoinitiators in food
      packaged at ng kg(-1) levels.

PMID- 21183188
TI  - Bicarbonate therapy for infants.

PMID- 21183187
TI  - Bowel habits and toilet training in rural and urban dwelling children in a
      developing country.
AB  - OBJECTIVES: To determine the bowel habits and toilet training of developmentally
      normal children ages 5 to 8 years in rural and urban areas of the province of
      Sindh, Pakistan. STUDY DESIGN: We conducted a descriptive cross-sectional study,
      conducted at households of rural (District Khairpur) and urban (Karachi) areas of
      Sindh, Pakistan, which enrolled 1000 children between 5 and 8 years of age, (half
      from rural and half from urban areas). A questionnaire regarding age, ethnicity,
      and sex was completed by two separate investigators from each setting. Recall
      information was elicited about bowel habits for the previous 2 weeks and the
      frequency and quality of stools, size of stools, and dietary habit for the
      previous 24 hours. A constipation score that was based on modified Rome III
      criteria was developed for each child. RESULTS: Functional constipation was
      reported 1.6 times more in the rural than the urban population (P < .001). Toilet
      training was initiated and completed earlier in the urban (18.6 +/- 6.8 and 46 +/
      12.5 months) than the rural children (28.6 +/- 6.1 and 56.5 +/- 6.7 months) (P <
      .001). The daily calorie, macronutrient, fiber, and water intake was higher in
      the urban population (P < .001). Functional constipation was significantly (P =
      .016) negatively correlated (r = -0.076) with the fiber intake. CONCLUSIONS:
      Functional constipation was found more frequently in the rural area. Toilet
      training was initiated and completed significantly earlier in the urban
      population.

PMID- 21183189
TI  - Influence of age and gender in motor performance in healthy subjects.
AB  - BACKGROUND/OBJECTIVES: Slowing of motor performance in human aging is a well
      demonstrated clinical observation. Information on the influence of gender in
      motor performance is less well-established. With the aim of analyzing the
      possible influence of age and gender in motor performance, we studied basic motor
      function in a large series of healthy sex-matched individuals aged >40 years.
      METHODS: We studied 246 subjects (123 males and 123 females; mean age 63.67 +/-
      10.79 and 63.61 +/- 11.04 years, respectively), stratified by age in 7 groups for
      each gender. Evaluation included four timed tests (pronation-supination, finger
      tapping and movement between two points, all with both hands, and walking test),
      and the three tests performed on a personal computer (speed for pressing
      repetitively a key - frequency, visual reaction time and movement time, all with
      both hands). Statistical analysis included two-way analysis of variance (ANOVA)
      for two factors (age and gender) and Pearson's or Spearman's correlation tests
      where appropriate. RESULTS: The analysis of motor performance between subgroups
      showed a clear influence of age on motor performance of all the tests, with the
      exception of the left visual reaction time. The results of all the motor tests
      performed were inversely correlated with age. Gender influenced the performance
      (the speed of motor performance was significantly better in males) of all the
      tasks with the exception of left pronation-supination, and left and right visual
      reaction time. CONCLUSION: Our results confirm in a large series of healthy
      subjects that basic motor performance deteriorates with age and is influenced by
      gender.

PMID- 21183190
TI  - Marine science and management means tackling exogenic unmanaged pressures and
      endogenic managed pressures--a numbered guide.

PMID- 21183191
TI  - Bather density as a predominant factor for health effects related to recreational
      bathing: results from the Greek bathers cohort study.
AB  - Our aim was to examine the health effects on bathers from exposure to
      recreational seawater on three beaches with different microbiology quality and
      bather density through a cohort study. An initial questionnaire and a 10 day
      follow up were used. Univariate and backward logistic regression analyses were
      used to asses the risk of developing symptoms or diseases among the bathers. In
      total, 3805 bathers were included in the study and 149 samples were collected
      from the three beaches. Despite all the beaches being characterized of high
      quality the levels of bacterial indicators differed among them. Health effects
      among bathers were not associated with bacterial indicators. A statistically
      significant increased risk for symptoms related to respiratory illness,
      gastroenteritis, medical consultation and use of medication was observed among
      bathers at the higher bather density beaches. Beach bather numbers should always
      be taken into account when considering a risk assessment approach.

PMID- 21183192
TI  - Emergency admissions for coronary heart disease: a cross-sectional study of
      general practice, population and hospital factors in England.
AB  - OBJECTIVES: Coronary heart disease (CHD) is a common reason for emergency
      admission in England. The objective of this study was to determine the
      association between general practice, population and hospital characteristics,
      including quality and outcomes framework (QOF) scores, with emergency admissions
      for angina, which is an ambulatory-care-sensitive condition, and myocardial
      infarction (MI). STUDY DESIGN: Cross-sectional study using hospital episode
      statistics, population and primary care data. METHODS: Pooled admissions
      (2005/2006) for all general practices in England adjusted for age and gender.
      Main outcome measures were relative rates of admission [incidence rate ratio
      (IRR)] for general practices adjusted for confounding variables in a multiple
      regression Poisson model. RESULTS: There were 80,377 admissions for angina and
      62,373 admissions for MI for individuals aged >=45 years. Characteristics
      positively associated with admission were deprivation [angina IRR 1.084 (95%
      confidence interval 1.052-1.117) per quartile increase, MI IRR 1.018 (95%
      confidence interval 1.009-1.028)], practice prevalence of CHD and smoking. Living
      in an urban area and closer to the emergency department increased the risk of
      admission for angina. Higher overall clinical QOF score was negatively associated
      with the risk of admission for angina. Training practices and higher numbers of
      general practitioners per registered population were associated with lower rates
      of MI admission. Practice size and condition-specific quality markers for CHD
      were not associated with the risk of admission. CONCLUSIONS: There is no
      clinically significant relationship between better quality of primary care, as
      measured by disease-specific QOF measures, and fewer CHD admissions. Deprivation,
      CHD prevalence and smoking are major risk factors for emergency admission for
      CHD.

PMID- 21183193
TI  - Hematological and biochemical studies of stephanofilarial dermatitis in naturally
      infected cattle of West Bengal, India.
AB  - This experimental study was conducted to assess the alterations in
      hematobiochemical values of cattle infected with stephanofilarial microfilariae.
      Hematological studies of infected cattle revealed significant (P<0.05) decrease
      in Hb%, PCV and TEC values whereas TLC values were significantly (P<0.05)
      increased. There was insignificant increase in lymphocyte concentration (%),
      significant (P<0.05) increase in eosinophil concentration (%) and insignificant
      decrease in neutrophil concentration (%) in infected cattle in relation to
      control animal. Biochemical studies revealed that the values of glucose, alkaline
      phosphatase, AST and ALT were significantly (P<0.05) increased in infected cattle
      than control cattle. However, the value of total serum protein was not affected.

PMID- 21183194
TI  - [Spinal extradural arachnoid cyst].

PMID- 21183195
TI  - Sonodynamic action of pyropheophorbide-a methyl ester induces mitochondrial
      damage in liver cancer cells.
AB  - Sonodynamic therapy with pyropheophorbide-a methyl ester (MPPa) presents a
      promising aspect in treating liver cancer. The present study aims to investigate
      the mitochondrial damage of liver cancer cells induced by MPPa-mediated
      sonodynamic action. Mouse hepatoma cell line H(22) cells were incubated with MPPa
      (2 MUM) for 20 h and then exposed to ultrasound with an intensity of 0.97 W/cm(2)
      for 8 s. Cytotoxicity was investigated 24h after sonodynamic action using MTT
      assay and light microscopy. Mitochondrial membrane potential (DeltaPsim) was
      analyzed using flow cytometry with rhodamine 123 staining and ultrastructural
      changes were observed using transmission electron microscopy (TEM). The
      cytotoxicity of MPPa-mediated SDT on H(22) cell line was 73.00+/-3.42%, greater
      than ultrasound treatment alone (28.12+/-5.19%) significantly while MPPa
      treatment alone had no significant effect on H(22) cells. Moreover, after MPPa
      mediated SDT cancer cells showed swollen mitochondria under TEM and a significant
      collapse of mitochondrial membrane potential. Our findings demonstrated that MPPa
      mediated SDT could remarkably induce cell death of H(22) cells, and highlighted
      that mitochondrial damage might be an important cause of cell death induced by
      MPPa-mediated SDT.

PMID- 21183196
TI  - Simulation of Lamb wave's interactions with transverse internal defects in an
      elastic plate.
AB  - Lamb wave's interactions with transverse internal defects in an elastic plate are
      investigated in this paper to help practical inspection work with guided wave. A
      2D frequency domain hybrid boundary element method approach previously mainly
      used to study Lamb wave's interactions with external defects in elastic plates is
      adopted in this work and extended to study the cases of internal defects.
      Simulation examples are presented to illustrate the reflection and transmission
      coefficients' variations with various parameters including defect's height,
      width, testing fd for internal symmetrical and non-symmetrical cracks, with
      symmetry defined with respect to the middle plane of the plate. This simulation
      could be a valuable tool for the research of Lamb wave's applications in
      nondestructive testing (NDT) field, as the problem of internal defects could be
      difficult to study experimentally because of the inconvenience in machining
      internal defects in a real plate.

PMID- 21183198
TI  - Virus disinfection in water by biogenic silver immobilized in polyvinylidene
      fluoride membranes.
AB  - The development of innovative water disinfection strategies is of utmost
      importance to prevent outbreaks of waterborne diseases related to poor treatment
      of (drinking) water. Recently, the association of silver nanoparticles with the
      bacterial cell surface of Lactobacillus fermentum (referred to as biogenic silver
      or bio-Ag(0)) has been reported to exhibit antiviral properties. The microscale
      bacterial carrier matrix serves as a scaffold for Ag(0) particles, preventing
      aggregation during encapsulation. In this study, bio-Ag(0) was immobilized in
      different microporous PVDF membranes using two different pre-treatments of bio
      Ag(0) and the immersion-precipitation method. Inactivation of UZ1 bacteriophages
      using these membranes was successfully demonstrated and was most probably related
      to the slow release of Ag(+) from the membranes. At least a 3.4 log decrease of
      viruses was achieved by application of a membrane containing 2500 mg bio
      Ag(0)(powder) m(-2) in a submerged plate membrane reactor operated at a flux of
      3.1 L m(-2) h(-1). Upon startup, the silver concentration in the effluent
      initially increased to 271 MUg L(-1) but after filtration of 31 L m(-2), the
      concentration approached the drinking water limit ( = 100 MUg L(-1)). A virus
      decline of more than 3 log was achieved at a membrane flux of 75 L m(-2) h(-1),
      showing the potential of this membrane technology for water disinfection on small
      scale.

PMID- 21183197
TI  - Novel approaches in anti-arenaviral drug development.
AB  - Hemorrhagic fevers caused by arenaviruses are among the most devastating emerging
      human diseases. Considering the number of individuals affected, the current lack
      of a licensed vaccine, and the limited therapeutic options, arenaviruses are
      arguably among the most neglected tropical pathogens and the development of
      efficacious anti-arenaviral drugs is of high priority. Over the past years
      significant efforts have been undertaken to identify novel potent inhibitors of
      arenavirus infection. High throughput screening of small molecule libraries
      employing pseudotype platforms led to the discovery of several potent and broadly
      active inhibitors of arenavirus cell entry that are effective against the major
      hemorrhagic arenaviruses. Mechanistic studies revealed that these novel entry
      inhibitors block arenavirus membrane fusion and provided novel insights into the
      unusual mechanism of this process. The success of these approaches highlights the
      power of small molecule screens in antiviral drug discovery and establishes
      arenavirus membrane fusion as a robust drug target. These broad screenings have
      been complemented by strategies targeting cellular factors involved in productive
      arenavirus infection. Approaches targeting the cellular protease implicated in
      maturation of the fusion-active viral envelope glycoprotein identified the
      proteolytic processing of the arenavirus glycoprotein precursor as a novel and
      promising target for anti-arenaviral strategies.

PMID- 21183199
TI  - Enhanced retention of linuron, alachlor and metalaxyl in sandy soil columns
      intercalated with wood barriers.
AB  - A study has been made of the effect a reactive barrier made of pine (softwood) or
      oak (hardwood) wood intercalated in a sandy soil column has on the retention of
      linuron, alachlor and metalaxyl (pesticides with contrasting physicochemical
      characteristics). The leaching of pesticides has been carried out under a
      saturated flow regime and breakthrough curves (BTCs) have been obtained at flow
      rates of 1 m Lmin(-1) (all pesticides) and 3 m Lmin(-1) (linuron). The cumulative
      curves in the unmodified soil indicate a leaching of pesticides >80% of the total
      amount of compound added. After barrier intercalation, linuron leaching decreases
      significantly and a modification of the leaching kinetics of alachlor and
      metalaxyl has been observed. The theoretical R factors increased ~2.6-3.3, 1.2
      1.6-fold, and 1.4-1.7-fold and the concentration of the maximum peak decreased ~6
      12-fold, 2-4-fold and 1.2-2-fold for linuron, alachlor and metalaxyl,
      respectively. When considering the three pesticides, significant correlations
      have been found between the theoretical retardation factor (R) and the pore
      volume corresponding to the maximum peaks of the BTCs (r=0.77; p<0.05) or the
      total volume leached (r=-0.78; p<0.05). The results reveal the efficacy of
      reactive wood barriers to decrease the leaching of pesticides from point sources
      of pollution depends on the type of wood, the hydrophobicity of the pesticide and
      the adopted water flow rate. Pine was more effective than oak in decreasing the
      leaching of hydrophobic pesticide linuron or in decreasing the maximum peak
      concentration of the less hydrophobic pesticides in soils. Efficacy of these wood
      barriers was limited for the least hydrophobic pesticide metalaxyl.

PMID- 21183200
TI  - The weight method: a new screening method for estimating pesticide deposition
      from knapsack sprayers in developing countries.
AB  - Investigations of occupational and environmental risk caused by the use of
      agrochemicals have received considerable interest over the last decades. And yet,
      in developing countries, the lack of staff and analytical equipment as well the
      costs of chemical analyses make it difficult, if not impossible, to monitor
      pesticide contamination and residues in humans, air, water, and soils. A new and
      simple method is presented here for estimation of pesticide deposition in humans
      and soil after application. The estimate is derived on the basis of water mass
      balance measured in a given number of high absorbent papers under low evaporative
      conditions and unsaturated atmosphere. The method is presented as a suitable,
      rapid, low cost screening tool, complementary to toxicological tests, to assess
      occupational and environmental exposure caused by knapsack sprayers, where there
      is a lack of analytical instruments. This new method, called the "weight method",
      was tested to obtain drift deposition on the neighbouring field and the clothes
      of the applicator after spraying water with a knapsack sprayer in one of the
      largest areas of potato production in Colombia. The results were confirmed by
      experimental data using a tracer and the same set up used for the weight method.
      The weight method was able to explain 86% of the airborne drift and deposition
      variance.

PMID- 21183202
TI  - The Neanderthal face is not cold adapted.
AB  - Many morphological features of the Pleistocene fossil hominin Homo
      neanderthalensis, including the reputed large size of its paranasal sinuses, have
      been interpreted as adaptations to extreme cold, as some Neanderthals lived in
      Europe during glacial periods. This interpretation of sinus evolution rests on
      two assumptions: that increased craniofacial pneumatization is an adaptation to
      lower ambient temperatures, and that Neanderthals have relatively large sinuses.
      Analysis of humans, other primates, and rodents, however, suggests that the first
      assumption is suspect; at least the maxillary sinus undergoes a significant
      reduction in volume in extreme cold, in both wild and laboratory conditions. The
      second assumption, that Neanderthal sinuses are large, extensive, or even
      'hyperpneumatized,' has held sway since the first specimen was described and has
      been interpreted as the causal explanation for some of the distinctive aspects of
      Neanderthal facial form, but has never been evaluated with respect to scaling. To
      test the latter assumption, previously published measurements from two
      dimensional (2D) X-rays and new three-dimensional (3D) data from computed
      tomography (CT) of Neanderthals and temperate-climate European Homo sapiens are
      regressed against cranial size to determine the relative size of their sinuses.
      The 2D data reveal a degree of craniofacial pneumatization in Neanderthals that
      is both commensurate with the size of the cranium and comparable in scale with
      that seen in temperate climate H. sapiens. The 3D analysis of CT data from a
      smaller sample supports this conclusion. These results suggest that the
      distinctive Neanderthal face cannot be interpreted as a direct result of
      increased pneumatization, nor is it likely to be an adaptation to resist cold
      stress; an alternative explanation is thus required.

PMID- 21183201
TI  - DNA repair gene polymorphisms at XRCC1, XRCC3, XPD, and OGG1 loci in
      Maharashtrian population of central India.
AB  - Reduction in DNA repair capacity is associated with increased rates of birth
      defects, cancer, and accelerated ageing. Genetic polymorphisms in DNA repair
      genes might influence the repair activities of the enzymes predisposing
      individuals to cancer risk. Owing to the presence of these genetic variants,
      inter-individual and ethnic differences in DNA repair capacity have been observed
      in various populations. India harbors enormous genetic, cultural and linguistic
      diversity. The present study was undertaken to determine the allele and genotype
      frequencies of four non-synonymous SNPs, XRCC1 Arg399Gln (C>T, rs25487), XRCC3
      Thr241Met (G>A, rs861539), XPD Lys751Gln (T>G, rs13181), and OGG1 Ser326Cys (C>G,
      rs1052133) in the Maharashtrian population, residing in the Vidarbha region of
      central India and to compare them with HapMap and other Indian populations. The
      variant alleles of these polymorphisms have been found to be positively
      associated with different forms of cancer in several genetic epidemiological
      studies. The basic prevalence of these polymorphisms in the general population
      must be known to evaluate their significance in risk assessment in cancer and
      other phenotypes. About 215 healthy and unrelated individuals from the
      Maharashtrian population were genotyped for each of these four polymorphisms
      using PCR-RFLP. The allele and genotype frequency distribution at the four DNA
      repair gene loci among Maharashtrians revealed a characteristic pattern. To the
      best of our knowledge, this is the first report of these DNA repair gene
      polymorphisms in a central Indian population.

PMID- 21183203
TI  - Hourly predictive artificial neural network and multivariate regression trees
      models of Ganoderma spore concentrations in Rzeszow and Szczecin (Poland).
AB  - Ganoderma spores are one of the most airspora abundant taxa in many regions of
      the world, and are considered to be important allergens. The aerobiology of
      Ganoderma basidiospores in two cities in Poland was examined using the volumetric
      method, (Burkard and Lanzonii Spore Traps), from selected days in 2004, 2005 and
      2006. Spores of Ganoderma were present in the atmosphere from June to November,
      with peak concentrations generally occurring from late July to mid-October. ANN
      (artificial neural network) and MRT (multivariate regression trees), models
      indicated that atmospheric phenomenon, hour and relative humidity were the most
      important variables influencing spore content. The remaining variables (air
      temperature, dew point, air pressure, wind speed and wind direction), also
      contributed to the high network performance, (ratio above 1), but their impact
      was less distinct. Those results are consistent with the Spearman's rank
      correlation analysis.

PMID- 21183204
TI  - Loss rates of urban biocides can exceed those of agricultural pesticides.
AB  - Biocides and pesticides are used to control unwanted organisms in urban and
      agricultural areas. After application, they can be lost to surface waters and
      impair water quality. Several national consumption studies have shown that urban
      and agricultural use may be in the same range. It is difficult to judge whether
      this results in similar loadings of surface waters because there is a lack of
      sound, comparative studies addressing urban and agricultural losses
      simultaneously. The aim of this study is thus to relate the biocide and pesticide
      loads found in surface waters to their respective urban and agricultural usage
      (loss rates). To simultaneously assess the loss rates, we conducted a
      comprehensive field study in a catchment of mixed land use on the Swiss Plateau.
      The study area was divided into four sub-catchments with different degrees of
      urban and agricultural land use. In addition, we studied the only wastewater
      treatment plant, a combined sewer overflow and a storm sewer within the area.
      Rain events were sampled at high temporal resolution from March to November,
      2007. Information on agricultural applications was gained from local farmers. For
      urban uses, consumption estimations were conducted based on statistical and
      product information. Despite substantially lower amounts used, the measured loads
      of urban biocides were in the same range as the most widely-used agricultural
      pesticides. The lower usage was compensated by urban loss rates that were up to
      ten times higher than agricultural ones (0.6 to 15% for urban, 0.4 to 0.9% for
      agricultural compounds). For most biocides and pesticides, the loads were
      controlled by rain events. Besides the rain-controlled losses, some urban-used
      biocides (e.g. diazinon) showed a continuous load independent of rain events and
      season. This study demonstrates that in catchments with mixed land use,
      mitigation strategies have to pay sufficient attention to the urban sources.

PMID- 21183205
TI  - Greenhouse gas footprinting for small businesses--the use of input-output data.
AB  - To mitigate anthropogenic climate change greenhouse gas emissions (GHG) must be
      reduced; their major source is man's use of energy. A key way to manage emissions
      is for the energy consumer to understand their impact and the consequences of
      changing their activities. This paper addresses the challenge of delivering
      relevant, practical and reliable greenhouse gas 'footprint' information for small
      and medium sized businesses. The tool we describe is capable of ascribing parts
      of the total footprint to specific actions to which the business can relate and
      is sensitive enough to reflect the consequences of change. It provides a
      comprehensive description of all emissions for each business and sets them in the
      context of local, national and global statistics. It includes the GHG costs of
      all goods and services irrespective of their origin and without double
      accounting. We describe the development and use of the tool, which draws upon
      both national input-output data and process-based life cycle analysis techniques;
      a hybrid model. The use of national data sets the output in context and makes the
      results consistent with national and global targets, while the life cycle
      techniques provide a means of reflecting the dynamics of actions. The model is
      described in some detail along with a rationale and a short discussion of
      validity. As the tool is designed for small commercial users, we have taken care
      to combine rigour with practicality; parameterising from readily available client
      data whilst being clear about uncertainties. As an additional incentive, we also
      report on the potential costs or savings of switching activities. For users to
      benefit from the tool, they need to understand the output and know how much
      confidence they should place in the results. We not only describe an application
      of non-parametric statistics to generate confidence intervals, but also offer
      users the option of and guidance on adjusting figures to examine the sensitivity
      of the model to its components. It is important that the user does not see the
      model as a calculator that will generate one truth, but as a method of gaining
      insight and informing management decisions. We describe its application in
      tourism businesses in North West England as a demonstrator for the service sector
      remote from simple primary production, with brief case studies. We discuss its
      success compared to traditional approaches and outline further development work.

PMID- 21183206
TI  - Characterization of road traffic noise exposure and prevalence of hypertension in
      central Taiwan.
AB  - Epidemiological studies have demonstrated that road traffic noise exposure is
      associated with hypertension in European, but the associations related to traffic
      sources and in other population are unclear. This study investigated the
      association between road traffic noise exposure and the prevalence of diagnosed
      hypertension among 321 male and 499 female resided near main roads in Taichung,
      Taiwan. Road traffic noise levels and traffic flow rates were measured
      simultaneously during 0900-1700 on weekdays in 2008. Multivariate logistic
      regressions were applied to estimate odds ratios (ORs) for hypertension by
      adjusting for potential confounders. Road traffic noise levels were significantly
      associated with traffic flow rates of motorcycles, light-duty gasoline vehicles,
      light-duty diesel trucks and heavy-duty diesel trucks and had the highest
      correlation with motorcycles. Per one unit (vehicle per hour) increase in the log
      transformed traffic flow rate of motorcycles was significantly related to the
      increment of 7.20+/-1.40 A-weighted decibels (dBA) in the traffic noise exposure.
      The high-exposure group (82.2+/-1.7dBA, n=358) had the significantly higher
      prevalence of hypertension (adjusted OR=2.15, 95% CI=1.08-4.26) than the low
      exposure group (77.2+/-1.6dBA, n=462). There was an increasing trend (p=0.023)
      between the prevalence of hypertension and residents exposed to <77dBA, 77-80dBA,
      80-83dBA and >=83dBA, respectively. Such an association was pronounced after
      adjusting for the total traffic flow rate. The study findings suggest that road
      traffic noise exposure may be associated with hypertension and the dominant
      source of traffic noise is motorcycles in central Taiwan.

PMID- 21183207
TI  - Mercury exposure in female artisanal small-scale gold miners (ASGM) in Mongolia:
      An analysis of human biomonitoring (HBM) data from 2008.
AB  - BACKGROUND: Many poor in developing countries have turned to artisanal small
      scale gold mining (ASGM) in an attempt to improve their situation. However, the
      mercury used to extract gold from ore is discharged in vaporized form into the
      environment, where it poses a hazard for human health. METHODS: As part of an
      environmental epidemiological study in Mongolia-to evaluate the burden of
      environmental mercury contamination-urine, blood and hair samples were collected
      from residents of areas with or without mercury contamination. A total of 200
      blood, urine and hair samples were analyzed for mercury and divided into three
      subgroups according to mercury content: (1) occupational exposure (high/medium);
      (2) environmental exposure (low); and (3) no exposure. Internal mercury
      distributions of the subgroups were compared using the Kruskal-Wallis and Mann
      Whitney U-test. The Chi-square test and likelihood ratio proportion were used to
      compare the findings with threshold limits. RESULTS: The highest values and
      greatest differences were seen in the urine samples (p<0.001, Kruskal-Wallis).
      The occupational group showing the highest exposure with a median mercury level
      of 4.36MUg/l (control group: 0.10MUg/l, p<0.001), 7.18MUg/g creatinine and 12
      results above the threshold limit HBM I (Human Biomonitoring I). Even
      participants from the low-exposure subgroup showed elevated mercury levels
      (median 2.88MUg/l urine and 2.98MUg/g creatinine, p<0.001), with 10 individuals
      above the HBM I threshold limits. DISCUSSION: The body burden resulting from the
      use of mercury in artisanal gold mining is high not only in the miners
      themselves, an increased mercury hazard was also found for inhabitants of mining
      areas who were not actively involved in mining. Public health support measures
      are urgently needed to alleviate the situation.

PMID- 21183208
TI  - Antithrombotic effects of ethanol extract of Crataegus orientalis in the
      carrageenan-induced mice tail thrombosis model.
AB  - INTRODUCTION: Crataegus species (common name is Hawthorn) are medicinal plants,
      which have flavonoids, triterpene acids, proanthocyanidins, and organic acids as
      main constituents, used in the treatment of cardiovascular diseases. One of the
      main causes of multiple cardiovascular diseases is intravascular thrombosis and
      current agents, which are used for the treatment and prevention of thrombosis,
      have some side effects. Therefore, new antithrombotic and thrombolytic agents are
      still needed. MATERIALS AND METHODS: Antithrombotic function of ethanol extract
      of Crataegus orientalis (COE) leaves was investigated in carrageenan-induced mice
      tail thrombosis model. Mice were injected with 40 MUl (1%) carrageenan (Type I)
      dissolved in physiological saline by intraplantar administration in the right
      hind paw. After carrageenan injection, the extract was administered at the doses
      of 100, 200, and 300 mg/kg. Heparin was used as a positive control (10 and 100
      IU). The length of tail-thrombosis was measured at 24th, 48th, and 72nd hours.
      RESULTS AND CONCLUSION: 100mg/kg COE and 10IU heparin were not significant when
      compared to control groups at the time interval (24-72 h) that results was
      obtained. At 24th hour, both 200 and 300 mg/kg of COE showed a significant
      antithrombotic activity (p<0.05 and p<0.01, respectively). However, 200 mg/kg COE
      lost its significance and there was a decrease in the significance values of 300
      mg/kg COE (p<0.05) at 48 and 72 h. From these results, it was concluded that COE
      significantly inhibited carrageenan-induced mice tail thrombosis in vivo.

PMID- 21183209
TI  - Aprotinin, but not tranexamic acid, is associated with increased pulmonary
      microvascular fibrin deposition after cardiac surgery.

PMID- 21183210
TI  - Examining the effect of minority status and neighborhood characteristics on
      cervical cancer survival outcomes.
AB  - OBJECTIVE: Understanding the factors that contribute to mortality and survival is
      central to health outcome research. The purpose of this study was to investigate
      the following: (1) differences in survival status by ethnicity and neighborhood
      median income level; and (2) individual- and neighborhood-level factors
      influencing cervical cancer survival. METHODS: This study was based on data from
      1811 cervical cancer cases obtained through the California Cancer Surveillance
      Program. The dependent variable was days of survival from date of cancer
      diagnosis. Zip code-based neighborhood-level variables were obtained from Census
      2000 data. RESULTS: Ethnicity was significantly associated with survival
      (chi2=20.58; p<0.001), with African-Americans showing the shortest survival. The
      5-year survival rates of European-, African-, Latino-, and Asian-American
      patients for all stages combined were 85%, 75%, 85%, and 84%, respectively.
      Differences in survival between high- and low-income regions were not observed.
      However, when ethnicity was considered, Asian-Americans who lived in high-income
      regions showed longer survival than their low-income community counterparts
      (chi2=4.531; p<0.05). The multilevel model demonstrated ethnicity, age at
      diagnosis, and cancer stage stratified by surgery to be significantly associated
      with cervical cancer survival at the individual level. At the neighborhood level,
      residing in neighborhoods with a high proportion of African-Americans increased
      the risk of death by 1%. CONCLUSIONS: The neighborhood context may be an
      influential contributor to survival for Asian- and African-Americans
      specifically. These findings necessitate closer examination of the unique
      contribution of ethnicity and neighborhood on cancer survival to disentangle the
      role of ethnic group membership, socio-ecological contexts and stress, and
      medical factors on disease outcomes.

PMID- 21183211
TI  - Incidence and timing of venous thromboembolism after surgery for gynecological
      cancer.
AB  - OBJECTIVE: This study aims to determine the incidence, timing, and risk factors
      of clinical venous thromboembolism. METHODS: A cohort of patients who had major
      gynecologic cancer surgery between 1998 and 2008 was identified. Secondarily, a
      nested case-control design wherein patients who had clinical VTE within 90 days
      after surgery were considered cases. Controls were matched on age, race, surgery
      date, and cancer site. Risk factors were evaluated for VTE within 90 days, and
      late VTE between 8 and 90 days. RESULTS: We identified 4158 women, 18 years or
      older, without a history of recent thrombosis. We observed 126 cases of clinical
      VTE within 90 days of surgery (incidence 4%) of which 96 (76%) occurred after
      post-operative day 7. In a multivariable model including age, ASA, BMI, race, and
      site of cancer, only ovarian cancer was a significant predictor for VTE within 90
      days (HR 2.8; 95% CI 1.6, 5.0). In the nested case-control study, we identified
      hospital stay >= 5 days (OR 2.8; 95% CI 1.5, 5.1) and prior VTE (OR 2.6; 95% CI
      1.1, 6.1) as significant risk factors for VTE within 90 days. Only hospital stay
      >= 5 days (OR 2.5; 95% CI 1.3, 4.7) was significantly associated with late VTE
      between 8 and 90 days. CONCLUSION: In gynecologic cancer patients, over 75% of
      VTE are detected more than 7 days after surgery. Patients with ovarian cancer,
      prolonged hospitalization, or a history of VTE are at highest risk of developing
      clinical VTE. Such patients would be optimal candidates for clinical trials
      evaluating extended VTE prophylaxis.

PMID- 21183213
TI  - Polymer-related off-target effects in non-viral siRNA delivery.
AB  - Since off-target effects in non-viral siRNA delivery are quite common but not
      well understood, in this study various polymer-related effects observed in
      transfection studies were described and their mechanisms of toxicity were
      investigated. A variety of stably luciferase-expressing cell lines was compared
      concerning polymer-mediated effects after transfection with polyplexes of siRNA
      and poly(ethylene imine) (PEI) or poly(ethylene glycol)-grafted PEI (PEG-PEI).
      Cell viability, LDH release, gene expression profiles of apoptosis-related genes
      and promoter activation were investigated. Interestingly, PEG-PEI, which is
      generally better tolerated than PEI, was found to activate apoptosis in a cell
      line- and concentration-dependent manner. While both polymers showed sigmoidal
      dose-response of cell viability in L929 cells (IC(50)(PEI) = 6 MUg/ml, IC(50)(PEG
      PEI) = 11 MUg/ml), H1299/Luc cells exhibited biphasic dose-response for PEG-PEI
      and stronger apoptosis at 2 MUg/ml than at 20 MUg/ml PEG-PEI, as shown in TUNEL
      assays. Gene expression profiling confirmed that H1299/Luc cells underwent
      apoptosis via thousand-fold activation of TNF receptor-associated factors.
      Additionally, it was demonstrated that NFkB-mediated CMV promoter activation in
      stably transfected cells can lead to increased target gene levels after
      transfection instead of siRNA-mediated knockdown. With these results, polymeric
      vectors were shown not to be inert substances. Therefore, alterations in gene
      expression caused by the delivery agent must be known to correctly interpret gene
      silencing experiments, to understand the mechanisms of off-target effects, and
      most of all to further develop vectors with reduced side effects. Taking these
      observations into account, one established cell line was eventually identified to
      be suitable for RNAi experiments. As shown by these experiments, materials that
      have been used for many years can elicit unexpected off-target effects.
      Therefore, non-viral vectors must be screened for several levels of toxicity to
      make them promising candidates.

PMID- 21183214
TI  - The potential of combinations of drug-loaded nanoparticle systems and adult stem
      cells for glioma therapy.
AB  - The prognosis of patients with malignant glioma remains extremely poor, despite
      surgery and improvements in radio- and chemo-therapies. Nanotechnologies hold
      great promise in glioma therapy as they protect the therapeutic agent and allow
      its sustained release. However, new paradigms permitting tumor-specific targeting
      and extensive intratumoral distribution must be developed to efficiently deliver
      nanoparticles. Modifications and functionalizations of nanoparticles have been
      developed to specifically track tumor cells. However, these nanoparticles have
      yielded few clinical results due to intra-patient heterogeneity and inter-patient
      variability. Stem cells with a specific tropism for brain tumors could be used as
      delivery vehicles for nanoparticles. Indeed, these cells have a natural tendency
      to migrate and distribute within the tumor mass and they can also incorporate
      nanoparticles. Stem cell therapy combined with nanotechnology could be a
      promising tool to efficiently deliver drugs to brain tumors.

PMID- 21183215
TI  - Dual gene targeted multimeric siRNA for combinatorial gene silencing.
AB  - Simultaneous silencing of multiple up-regulated genes is an attractive and viable
      strategy to treat many incurable diseases including cancer. Herein we report that
      multimerized siRNA conjugate composed of two different siRNA sequences in the
      same backbone shows more efficient inhibition of the two corresponding target
      genes at one time than physically mixed multimerized siRNA conjugates. Two model
      siRNAs against VEGF and GFP gene were chemically crosslinked via cleavable and
      noncleavable linkages for the preparation of dual gene targeted multimeric siRNA
      conjugates (DGT multi-siRNA). Cleavable DGT multi-siRNA with reducible disulfide
      linkages exhibited significantly higher gene silencing efficiencies at mRNA and
      protein expression levels than noncleavable DGT multi-siRNA, the physical mixture
      of naked siRNA, and that of single gene targeted multimeric siRNA (SGT multi
      siRNA) with eliciting negligible immune response. DGT multi-siRNAs against two
      therapeutic siRNAs, anti-survivin and anti-bcl-2 targeted siRNA, also showed
      greatly enhanced apoptotic effect. This approach for concurrent suppression of
      combinatorial therapeutic target genes using cleavable multimeric siRNA structure
      can be potentially used for improved therapeutic efficacy.

PMID- 21183216
TI  - Engineering complement activation on polypropylene sulfide vaccine nanoparticles.
AB  - The complement system is an important regulator of both adaptive and innate
      immunity, implicating complement as a potential target for immunotherapeutics. We
      have recently presented lymph node-targeting, complement-activating nanoparticles
      (NPs) as a vaccine platform. Here we explore modulation of surface chemistry as a
      means to control complement deposition, in active or inactive forms, on
      polypropylene sulfide core, block copolymer Pluronic corona NPs. We found that
      nucleophile-containing NP surfaces activated complement and became functionalized
      in situ with C3 upon serum exposure via the alternative pathway. Carboxylated NPs
      displayed a higher degree of C3b deposition and retention relative to
      hydroxylated NPs, upon which deposited C3b was more substantially inactivated to
      iC3b. This in situ functionalization correlated with in vivo antigen-specific
      immune responses, including antibody production as well as T cell proliferation
      and IFN-gamma cytokine production upon antigen restimulation. Interestingly,
      inactivation of C3b to iC3b on the NP surface did not correlate with NP affinity
      to factor H, a cofactor for protease factor I that degrades C3b into iC3b,
      indicating that control of complement protein C3 stability depends on
      architectural details in addition to factor H affinity. These data show that
      design of NP surface chemistry can be used to control biomaterials-associated
      complement activation for immunotherapeutic materials.

PMID- 21183212
TI  - Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995
      2007 (the International Cancer Benchmarking Partnership): an analysis of
      population-based cancer registry data.
AB  - BACKGROUND: Cancer survival is a key measure of the effectiveness of health-care
      systems. Persistent regional and international differences in survival represent
      many avoidable deaths. Differences in survival have prompted or guided cancer
      control strategies. This is the first study in a programme to investigate
      international survival disparities, with the aim of informing health policy to
      raise standards and reduce inequalities in survival. METHODS: Data from
      population-based cancer registries in 12 jurisdictions in six countries were
      provided for 2.4 million adults diagnosed with primary colorectal, lung, breast
      (women), or ovarian cancer during 1995-2007, with follow-up to Dec 31, 2007. Data
      quality control and analyses were done centrally with a common protocol, overseen
      by external experts. We estimated 1-year and 5-year relative survival,
      constructing 252 complete life tables to control for background mortality by age,
      sex, and calendar year. We report age-specific and age-standardised relative
      survival at 1 and 5 years, and 5-year survival conditional on survival to the
      first anniversary of diagnosis. We also examined incidence and mortality trends
      during 1985-2005. FINDINGS: Relative survival improved during 1995-2007 for all
      four cancers in all jurisdictions. Survival was persistently higher in Australia,
      Canada, and Sweden, intermediate in Norway, and lower in Denmark, England,
      Northern Ireland, and Wales, particularly in the first year after diagnosis and
      for patients aged 65 years and older. International differences narrowed at all
      ages for breast cancer, from about 9% to 5% at 1 year and from about 14% to 8% at
      5 years, but less or not at all for the other cancers. For colorectal cancer, the
      international range narrowed only for patients aged 65 years and older, by 2-6%
      at 1 year and by 2-3% at 5 years. INTERPRETATION: Up-to-date survival trends show
      increases but persistent differences between countries. Trends in cancer
      incidence and mortality are broadly consistent with these trends in survival.
      Data quality and changes in classification are not likely explanations. The
      patterns are consistent with later diagnosis or differences in treatment,
      particularly in Denmark and the UK, and in patients aged 65 years and older.
      FUNDING: Department of Health, England; and Cancer Research UK.

PMID- 21183217
TI  - The art of identification of extravillous trophoblast.
AB  - Immunohistochemical staining with specific markers for the respective cell type
      facilitates tracking and identification of cells such as extravillous trophoblast
      in the uterine wall. Cytokeratin has been recommended as a marker for all kinds
      of trophoblasts and is commonly used as a marker to identify interstitial as well
      as endovascular trophoblast. With immunohistochemical double staining of
      specimens of first trimester placental bed we show that staining with anti
      cytokeratin alone is not sufficient to track all routes of trophoblast invasion.
      Endovascular trophoblasts can be easily mixed up with endoglandular trophoblasts.
      Thus, additional application of specific markers for extravillous trophoblast
      such as anti-HLA-G is strongly recommended, ideally in combination with other
      markers in immunohistochemical or immunofluorescence double staining.

PMID- 21183219
TI  - Chronic histiocytic intervillositis of unknown etiology: clinical features in a
      consecutive series of 69 cases.
AB  - INTRODUCTION: Chronic histiocytic intervillositis of unknown etiology (CIUE) is a
      rare placental inflammatory disease, associated with severe obstetric
      complications. Its pathophysiologic mechanism remains to be elucidated. AIM: To
      establish anatomical-clinical correlations to improve our understanding of CIUE
      pathophysiology. MATERIAL AND METHODS: Retrospective study of all cases of CIUE
      occurring during a 9-year period in a university tertiary hospital center.
      RESULTS: CIUE was diagnosed in 69 pregnancies in 50 different women, after early
      spontaneous abortions (30.4%), late spontaneous abortions (13.0%), in utero
      deaths (26.1%), and live births (30.4%). Of 39 fetuses surviving to at least 22
      weeks, 24 had severe intrauterine growth restriction (61.5%) and 18 died in utero
      (46.2%). Twelve in utero deaths occurred before 32 weeks of gestation (66.7%).
      Substantially elevated alkaline phosphatase levels (>600 IU/L) were observed in
      55.6% of cases. Microscopic examination of placentas showed that both spontaneous
      early abortions and intrauterine growth restriction were significantly associated
      with more intense fibrin deposits. CONCLUSION: A diagnosis of CIUE must be
      considered in cases of severe obstetric complications. We hypothesize that the
      elevated alkaline phosphatases (ALP) observed during the pregnancy demonstrate
      the presence of syncytiotrophoblastic lesions due to histiocytosis in the
      intervillous space, before fibrin deposits cover them.

PMID- 21183218
TI  - Transcriptional profiling of human placentas from pregnancies complicated by
      preeclampsia reveals disregulation of sialic acid acetylesterase and immune
      signalling pathways.
AB  - The placenta plays an important role as a regulator of fetal nutrition and growth
      throughout development and placental factors contribute to gestational
      abnormalities such as preeclampsia. This study describes the genome-wide gene
      expression profiles of a large (n = 60) set of human placentas in order to
      uncover gene expression patterns associated with preeclampsia. In addition to
      confirming changes in expression of soluble factors associated with preeclampsia
      such as sFLT1 (soluble fms-like tyrosine kinase-1), sENG (soluble endoglin), and
      INHA (inhibin alpha), we also find changes in immune-associated signaling
      pathways, offering a potential upstream explanation for the shallow trophoblast
      invasion and inadequate uterine remodeling typically observed in pathogenesis of
      preeclampsia. Notably, we also find evidence of preeclampsia-associated placental
      upregulation of sialic acid acetylesterase (SIAE), a gene functionally associated
      with autoimmune diseases.

PMID- 21183220
TI  - Delayed biochemical changes induced by mercury intoxication are prevented by zinc
      pre-exposure.
AB  - This work evaluated the delayed effects of mercury and the effectiveness of zinc
      in preventing such effects. Pups were pre-treated with 1 daily dose of ZnCl(2)
      (27 mg/kg/day, by subcutaneous injections) from 3rd to 7th postnatal day and
      received 1 daily dose of 5 mg/kg of HgCl(2), for 5 subsequent days (8-12 days
      old). Animals were euthanized 21 days after the end of Hg-exposure.
      Porphobilinogen-synthase activity as well as zinc and mercury contents was
      determined in the liver and kidneys. Alanine aminotransferase, aspartate
      aminotransferase and lactic dehydrogenase activities as well as urea, creatinine
      and glucose levels were analyzed in plasma or serum. Some animals were considered
      more sensitive to mercury, since they did not recover the body weight gain and
      presented an increase of renal and hepatic mercury content, urea and creatinine
      levels; a decrease in renal porphobilinogen-synthase and alanine aminotransferase
      activities, as well as a decrease in the liver and an increase in kidney weights.
      Some animals were considered less sensitive to mercury because they recovered the
      body weight and presented no biochemical alterations in spite of mercury in the
      tissues. Zinc prevents partially or totally the alterations caused by mercury
      even those that persisted for a long time after the end of exposure. These
      findings suggest that there is difference among the animals regarding the
      sensitivity to mercury.

PMID- 21183221
TI  - Occurrence of sulfonamide residues along the Ebro River basin: removal in
      wastewater treatment plants and environmental impact assessment.
AB  - Sulfonamides (SAs) have become one of the antibiotic families most frequently
      found in all kind of environmental waters. In the present work, the presence of
      16 SAs and one of their acetylated metabolites in different water matrices of the
      Ebro River basin has been evaluated during two different sampling campaigns
      carried out in 2007 and 2008. Influent and effluent samples from seven wastewater
      treatment plants (WWTPs), together with a total of 28 river water samples were
      analyzed by on-line solid phase extraction-liquid chromathography-tandem mass
      spectrometry (on-line SPE-LC-MS/MS). Sulfamethoxazole and sulfapyridine were the
      SAs most frequently detected in WWTPs (96-100%), showing also the highest
      concentrations, ranging from 27.2 ng L(-1) to 596 ng L(-1) for sulfamethoxazole
      and from 3.7 ng L(-1) to 227 ng L(-1) for sulfapyridine. Sulfamethoxazole was
      also the SA most frequently detected in surface waters (85% of the samples) at
      concentrations between 11 ng L(-1) and 112 ng L(-1). In order to assess the
      effectiveness of the wastewater treatment in degrading SAs, removal efficiencies
      in the seven WWTPs were calculated for each individual SA (ranging from 4% to
      100%) and correlated to the corresponding hydraulic retention times or residence
      times of the SAs in the plants. SAs half-lives were also estimated, ranging from
      to 2.5 hours (sulfadimethoxine) to 128 h (sulfamethazine). The contribution of
      the WWTPs to the presence of SAs depends on both the load of SAs discharging on
      the surface water from the WWTP effluent but also on the flow of the receiving
      waters in the discharge sites and the dilution exerted; WWTP4 exerts the highest
      pressure on the receiving water course. Finally, the potential environmental risk
      posed by SAs was evaluated calculating the hazard quotients (HQ) to different non
      target organisms in effluent and river water. The degree of susceptibility
      resulted in algae>daphnia>fish. Sulfamethoxazole was the only SA posing a risk to
      algae in effluent water, with an HQ>7.

PMID- 21183222
TI  - Prevalence and correlates of respiratory and non-respiratory panic attacks in the
      general population.
AB  - BACKGROUND: Panic attacks are heterogeneous with regards to symptom profile.
      Subtypes of panic attacks have been proposed, of which the most investigated is
      respiratory panic attacks (RPA). Limited information exists about RPA in the
      general population. METHOD: The prevalence and correlates of RPA and non
      respiratory panic attacks (NRPA) were examined in a subsample (n=8.796) of
      individuals participating in a cross-sectional survey of the adult general
      population of six European countries. Panic attacks, mental disorders, and
      chronic physical conditions were assessed with the Composite International
      Diagnostic Interview (CIDI) 3.0. Data on use of health services and disability
      were obtained. RESULTS: The lifetime prevalence of RPA was 6.77 and the 12-month
      prevalence was 2.26. No robust associations of RPA with sociodemographic
      characteristics, mental disorders or physical conditions were found as compared
      to NRPA. RPA were associated with increased use of health services but similar
      disability in comparison to NRPA. LIMITATIONS: Few direct data are available on
      the validity of the CIDI to assess RPA. Other definitions of RPA exist in the
      literature. CONCLUSIONS: Our findings suggest that there are very few differences
      between RPA and NRPA and do not support the need of subtyping panic attacks in
      current classification systems.

PMID- 21183224
TI  - Is context everything to the definition of clinical depression? A test of the
      Horwitz and Wakefield postulate.
AB  - BACKGROUND: In arguing for the need to distinguish clinical depression from
      sadness, Horwitz and Wakefield argued for weighting consideration to nuances of
      life event stressors. Their definition of clinical depression corresponds to the
      concept of endogenous depression or melancholia, while their model would position
      reactive (or context specific) non-melancholic depressive disorders more as
      manifestations of 'sadness' rather than as clinical depression. METHOD: We test
      their postulate by examining the extent to which 141 clinically diagnosed
      melancholic and non-melancholic depressed patients reported episodes as being
      preceded by a life event stressor or not--and the salience of any life stressor
      to episode onset and severity. RESULTS: While melancholic patients were more
      likely than non-melancholic patients to report episodes coming 'out of the blue'
      and to be more severe than might be expected from the severity of antecedent
      stressors, differences were more ones of degree and not absolute. Such context
      variables appeared, however, to differentiate melancholic and non-melancholic
      patients more consistently than depression symptom variables. As depression
      severity and impairment levels did not differ across the melancholic and non
      melancholic patients, findings were unlikely to be artefacts of such factors.
      CONCLUSIONS: The study finds some support for the Horwitz and Wakefield
      hypothesis of clinical (or, at least melancholic) depression requiring
      independence of context or an antecedent stressor, but with precision likely to
      be compromised by nuances intrinsic to assessment of life event stressors and
      their contribution to depression onset, difficulties in defining valid
      'melancholic' and 'non-melancholic' depressive sub-groups and the parsimony of
      the hypothesis.

PMID- 21183223
TI  - Stress response circuitry hypoactivation related to hormonal dysfunction in women
      with major depression.
AB  - BACKGROUND: Women have approximately twice the risk of major depressive disorder
      (MDD) than men, yet this difference remains largely unexplained. Previous MDD
      research suggests high rates of endocrine dysfunction, which may be related to
      deficits in brain activity in stress response circuitry [hypothalamus, amygdala,
      hippocampus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC)]. This
      functional magnetic resonance imaging (fMRI) study investigated the relationship
      between hypothalamic-pituitary-gonadal (HPG)-axis hormones and stress response
      circuitry dysfunction in MDD in women. METHODS: During the late
      follicular/midcycle phase of the menstrual cycle, female participants (10 with
      extensive histories of MDD, in remission, 10 healthy controls) were scanned while
      viewing negative and neutral arousal pictures. Group differences in blood oxygen
      level dependent (BOLD) signal changes were analyzed using SPM2. Baseline gonadal
      hormones included estradiol, progesterone, and testosterone. RESULTS: fMRI
      results showed greater BOLD signal intensity changes in controls versus MDD in
      hypothalamus, amygdala, hippocampus, OFC, ACC, and subgenual ACC, findings
      unrelated to medication status. MDD women had a lower serum estradiol and higher
      serum progesterone compared to controls. Hypoactivations in hypothalamus,
      subgenual ACC, amygdala and OFC in MDD were associated with low estradiol and
      high progesterone. LIMITATIONS: Generalizability of our findings is limited by
      small sample size and restriction to females, although this did not affect the
      internal validity of the results. CONCLUSIONS: Hypoactivation of the stress
      response circuitry in MDD women is associated with dysregulation of the HPG-axis.
      Associations between brain activity deficits and hormonal disruption in MDD may
      ultimately contribute to understanding sex differences in MDD.

PMID- 21183225
TI  - Electroconvulsive therapy has acute immunological and neuroendocrine effects in
      patients with major depressive disorder.
AB  - BACKGROUND: Major depressive disorder is associated with alterations in the
      neuroendocrine as well as immune system. Few studies examined the impact of
      electroconvulsive therapy (ECT) on these systems in patients with major
      depressive disorder (MDD). METHODS: In this explorative study 12 patients
      suffering from medication-resistant MDD or MDD with psychotic features were
      studied during the first, the fifth and eleventh session of ECT. Blood samples
      were taken immediately prior to the electrostimulus and 5, 15 and 30 min after
      the electrostimulus to assess various lipopolysaccharide (LPS) stimulated or T
      cell mitogen induced cytokines, immune cell numbers, Natural Killer cell
      activity, cortisol and ACTH. RESULTS: Acute ECT increased the LPS-stimulated
      production of the cytokines IL-6 and TNF-alpha by peripheral monocytes but not
      the production of the anti-inflammatory cytokine IL-10. Acute ECT decreased T
      cell mitogen-induced levels of IFN-gamma but IL-10 and IL-4 levels were left
      unaffected while NK cell activity increased momentarily but significantly.
      Cortisol and ACTH rose significantly after electrostimulus. Repeated ECT had no
      significant effect on any of the parameters. LIMITATIONS: The study had a small
      group size. Also the patient group was heterogeneous as it consisted of patients
      with therapy-resistant depression with or without psychotic features.
      CONCLUSIONS: Results suggest that acute ECT is associated with transient
      immunological and neuro-endocrine changes, while repeated ECT does not have an
      additive effect on the immune and neuroendocrine functions.

PMID- 21183226
TI  - Association between three genetic polymorphisms of glutathione S-transferase Z1
      (GSTZ1) and susceptibility to schizophrenia.

PMID- 21183227
TI  - Local and systemic immune responses following infection of broiler-type chickens
      with avian Metapneumovirus subtypes A and B.
AB  - Infections with avian Metapneumovirus (aMPV) are often associated with swollen
      head syndrome in meat type chickens. Previous studies in turkeys have
      demonstrated that local humoral and cell-mediated immunity plays a role in aMPV
      infection. Previous experimental and field observations indicated that the
      susceptibility of broilers and their immune reactions to aMPV may differ from
      turkeys. In the presented study local and systemic immune reactions of broilers
      were investigated after experimental infections with subtypes A and B aMPV of
      turkey origin. Both virus subtypes induced a mild respiratory disease. The
      recovery from respiratory signs correlated with the induction of local and
      systemic aMPV virus-neutralizing antibodies, which began to rise at 6 days post
      infection (dpi), when the peak of clinical signs was observed. In a different
      manner to the virus neutralizing (VN) and IgG-ELISA serum antibody titres, which
      showed high levels until the end of the experiments between 24 and 28 dpi, the
      specific IgA-ELISA and VN-antibody levels in tracheal washes decreased by 10 and
      14 dpi, respectively, which may explain the recurring aMPV-infections in the
      field. Ex vivo cultured spleen cells from aMPV-infected broilers released at 3
      and 6 dpi higher levels of IFN-gamma after stimulation with Concanavalin A as
      compared to virus-free birds. In agreement with studies in turkeys, aMPV-infected
      broilers showed a clear CD4+ T cell accumulation in the Harderian gland (HG) at 6
      dpi (P<0.05). In contrast to other investigations in turkeys aMPV-infected
      broilers showed an increase in the number of CD8alpha+ cells at 6 dpi compared to
      virus-free birds (P<0.05). The numbers of local B cells in the Harderian gland
      were not affected by the infection. Both aMPV A and B induced up-regulation of
      interferon (IFN)-gamma mRNA-expression in the nasal turbinates, while in the
      Harderian gland only aMPV-A induced enhanced IFN-gamma expression at 3 dpi. The
      differences in systemic and local T cell and possibly natural killer cell
      activity in the HG between turkeys and chickens may explain the differences in
      aMPV-pathogenesis between these two species.

PMID- 21183228
TI  - The effect of a single prolonged milking interval on inflammatory parameters,
      milk composition and yield in dairy cows.
AB  - A technical stop in automatic milking systems may result in a severely prolonged
      milking interval (PMI) with subsequent impact on milk somatic cell count (SCC).
      This study investigated the inflammatory reaction, milk composition and yield
      during SCC peak observed in composite milk after exposing cows to a single PMI of
      24h. At the first milking after the PMI, a sharply increased proportion of milk
      polymorphonuclear leukocytes (PMN) but marginally increased SCC were observed.
      The peak in SCC was not seen until morning milking day 2 after the PMI, notably,
      concomitantly with a decreased PMN proportion. An increase in blood lactose, milk
      bovine serum albumin and serum amyloid A (SAA) and a drop in milk alpha
      lactalbumin (ALA) were seen concomitantly with the peak in PMN. All parameters
      mentioned, had returned to base line after day 2. The changes in SCC and SAA had
      the longest duration. Lactate dehydrogenase in afternoon milk was decreased
      during the whole study as was also afternoon milk yield. Interleukin-1beta could
      not be detected in milk at any time. SAA and ALA, respectively, may influence
      chemotaxis and the changed concentrations observed after the PMI might have
      contributed to the increased migration of PMN to milk.

PMID- 21183230
TI  - The external rhinoplasty approach for congenital nasal lesions in children.
AB  - OBJECTIVE: Congenital lesions of the nose can be challenging to excise. While
      some lesions carry infection risks, in most cases surgery is primarily performed
      for cosmesis. Some lesions may extend up to the skull base and this can
      occasionally be missed on MRI scans. Surgical access has to allow complete
      excision in all circumstances, but access must be balanced against cosmetic
      results. We present our experience of the external rhinoplasty approach which
      allows wide access with little visible scarring. METHODS: Retrospective chart
      review of all cases performed between November 2003 and October 2009. RESULTS: 15
      children underwent excisional surgery using the external rhinoplasty approach.
      They were aged 1-5 years at the time of surgery, and 12 were male. Pathology
      comprised congenital midline nasal dermoid cysts in 13 (of which 4 extended
      intracranially), extranasal glioma in 1 and non-resolving haemangioma in 1. The
      surgical approach provided adequate visualisation in all cases. The children with
      intracranial dermoids had resection and repair of the dura as part of their
      procedure. No post-operative CSF leaks occurred. One child with nasal dermoid had
      a small cyst recurrence in the skin of the nasal tip requiring further surgery
      but no deep recurrences occurred. Follow up ranges from 3 months to 6 years.
      Children with widened nasal bones before surgery have all shown rapid bony
      remodelling after surgery. CONCLUSIONS: The external rhinoplasty approach offers
      excellent access in young children, even for intracranial lesions.

PMID- 21183229
TI  - Chronic stress promotes lymphocyte reduction through TLR2 mediated PI3K signaling
      in a beta-arrestin 2 dependent manner.
AB  - Physical and psychological stress can alter the immune system in both humans and
      animals. Stress is a known risk factor for numerous human diseases, such as
      infectious and autoimmune diseases, and cancer. Toll-like receptors (TLRs) play a
      pivotal role in the induction of innate and adaptive immune response. Our
      previous studies have shown that TLR4 deficiency prevents stress-induced
      splenocyte reduction. However, the role of TLR2 in stress-mediated lymphocyte
      reduction is unknown. In this study, we investigated the effects of TLR2 ligands
      on stress-induced lymphocyte reduction. We also defined whether the
      phosphoinositide 3-kinases (PI3Ks)/Akt pathway contributes to TLR2-mediated
      lymphocyte numbers altered by stress. Our data have shown that stimulation of
      TLR2 by TLR2 ligands peptidoglycan (PGN) or Pam3CSK4 (Pam3) attenuates stress
      induced reduction in lymphocyte numbers. However, TLR2 ligand-induced protection
      from stress-induced lymphocyte reduction is lost in TLR2 deficiency in mice.
      Furthermore, stimulation of TLR2 by PGN induces protection from stress-induced
      reduction in the number of splenocytes through PI3K. Moreover, PGN dramatically
      increases the level of phosphorylation of Akt through a PI3K-dependent manner.
      Moreover, we found that stimulation of TLR2 by PGN induced protection from stress
      induced reduction in splenocyte numbers is abolished in beta-arrestin 2 deficient
      mice. In addition, PGN-induced immune protection in stress-induced changes of
      cytokine levels appears to require beta-arrestin 2, a multifunctional adaptor and
      signal transducer. Collectively, our study thus demonstrates that stimulation of
      TLR2-mediated PI3K signaling attenuates splenocyte reduction induced by stress,
      and that beta-arrestin 2 modulates TLR2-mediated immune response following
      stress.

PMID- 21183231
TI  - Impact of mandibular two-implant retained overdentures on life quality in a group
      of elderly Turkish edentulous patients.
AB  - The aim of the study was to examine the influence of mandibular two-implant
      retained overdentures on life quality of elderly Turkish patients. The study
      population comprised 78 edentulous complete denture wearers (aged 65-82) seeking
      implant-retained mandibular overdentures at Istanbul University, Turkey. Every
      patient received 2 dental implants in the interforaminal region of the mandible
      and maxillary conventional dentures and mandibular implant retained overdentures
      6 weeks after surgery. Turkish versions of oral health impact profile (OHIP-14)
      and the United Kingdom oral health-related quality of life (OHQoL-UK) were used
      for the evaluation of life quality before and after treatment. Compared to
      pretreatment scores, subjects had statistically significant improvements in life
      quality after receiving new dentures (p < 0.05). Based on these results, it can
      be concluded that mandibular two-implant retained overdentures improve the life
      quality of elderly edentulous Turkish patients.

PMID- 21183232
TI  - Duration and magnitude of the effect of a single statin tablet in primary
      prevention of cardiovascular events.
AB  - BACKGROUND: Many preventative steps are recommended for both regular and
      opportunistic use. However statins are recommended exclusively for lifelong use:
      opportunistic uptake is blocked by lack of evidence of benefit. METHOD: This
      manuscript presents and applies a method of quantifying cardiovascular event
      prevention from a single statin tablet, using data from trials of regular
      administration. It calculates sample sizes required for direct experimental
      verification. RESULTS: The progressive growth of relative-risk reduction is shown
      to directly reflect progressive delivery of prevention from the first tablet.
      Regular-administration trial data expose the time course of preventative effect
      of a single tablet. From 90,056 patients' trial data, event-prevention of a
      single statin tablet is found to develop gradually over one year. Each tablet of
      (modest) statin gives 0.137% relative reduction in annual mortality over one
      year. For an average 60-year-old UK man, absolute mortality reduction is 143
      millionths of a percent (47 times larger than the survival benefit of him wearing
      a seatbelt once). Verification by 1-year trial would need 300 million subjects. A
      1-month trial would need 4 billion, the majority of the world's population.
      CONCLUSION: It is patient, but innumerate, to await direct trial evidence of
      opportunistic primary prevention by one statin tablet. Regular-administration
      trials show that each tablet delivers event reduction gradually over 1 year.
      Although the absolute death reduction seems small, for men over 35 it is larger
      than death reduction from wearing a seatbelt for a car journey. Physicians
      currently encourage opportunistic uptake of exercise, but not statins.
      Opportunistic pharmaceutical prevention should not be rejected without more valid
      grounds than lack of explicit trials.

PMID- 21183233
TI  - Echocardiography for assessment of regional and global right ventricular systolic
      function in adults with repaired tetralogy of Fallot.
AB  - BACKGROUND: The right ventricular (RV) systolic function is important for
      decision making in adults with repaired tetralogy of Fallot (rTOF). Our aim was
      to assess regional RV systolic function and its impact on global RV systolic
      function by echocardiography. METHODS: In 101 adults with rTOF, regional RV
      systolic function on echocardiography was compared to 50 individuals with
      structurally normal hearts. In patients with rTOF, the impact of
      echocardiographic measures of regional RV systolic function on global RV-ejection
      fraction as measured by cardiac magnetic resonance imaging (CMR-RVEF) was
      determined. RESULTS: Compared to normals, patients with rTOF had impaired
      systolic function of the RV outflow tract. Patients with rTOF and normal CMR-RVEF
      compensate this loss of RV outflow tract function with increased contractions of
      the RV-body, measured as fractional area change on short axis (30+/-12% versus
      19+/-7%, p<0.0001) and on 4-chamber views (42+/-7% versus 38+/-8%, p=0.06). In
      contrast, patients with rTOF and abnormal global CMR-RVEF showed significantly
      lower systolic function of the RV-body compared to normal controls (fractional
      area change on 4-chamber view: 31+/-6% versus 38+/-8%, p<0.0001). A simple
      regression model, incorporating fractional shortening of RV outflow tract and
      fractional area change on 4-chamber view allows accurate echocardiographic
      estimation of the CMR-derived RVEF. CONCLUSIONS: Patients with repaired tetralogy
      of Fallot have markedly different regional systolic RV-function compared to
      normals, even when the global RV systolic function is preserved. The systolic
      function of the RV outflow tract and of the RV body are both important
      determinants of global systolic RV function in these patients. Their prognostic
      significance needs to be determined.

PMID- 21183234
TI  - Observations of variable inter-observer agreement for clinical evaluation of
      faecal consistency in grow-finishing pigs.
AB  - Inter-observer agreement for assessment of faecal consistency in pigs was
      evaluated using a scoring system with 3 categories. In a pilot study, 3 observers
      performed an examination of faecal samples post-collection. The samples were
      obtained from pigs (12-13 weeks old) in 4 herds with a history of diarrhoea
      associated with Lawsonia intracellularis, Brachyspira spp. and/or Porcine
      Circovirus Type 2. Observer 1 examined all the faecal samples from the 4 herds.
      Observer 2 only examined the faecal samples from herds 1 and 2. Observer 3 only
      examined the faecal samples from herds 3 and 4. We observed a substantial
      agreement in faecal consistency scores between Observers 1 and 3 (kappa=0.64, 95%
      CI: 0.51-0.78). In contrast, only a fair agreement was observed between Observers
      1 and 2 (kappa=0.24, 95% CI: 0.14-0.34). The variations in inter-observer
      agreement detected in the current study suggest that misclassification error can
      be a problem in studies assessing faecal consistency. Solutions may include
      developing a standardized system for scoring the consistency of pig faeces,
      calibration when more than one observer is involved in clinical studies and using
      a more objective measure of faecal consistency.

PMID- 21183236
TI  - Public vs. private provision of charity care? Evidence from the expiration of
      Hill-Burton requirements in Florida.
AB  - This paper explores the consequences of the expiration of charity care
      requirements imposed on private hospitals by the Hill-Burton Act. We examine
      delivery care and the health of newborns using the universe of Florida births
      from 1989 to 2003 combined with hospital data from the American Hospital
      Association. We find that charity care requirements were binding on hospitals,
      but that private hospitals under obligation "cream skimmed" the least risky
      maternity patients. Conditional on patient characteristics, they provided less
      intensive maternity services but without compromising patient health. When
      obligations expired, private hospitals quickly reduced their charity caseloads,
      shifting maternity patients to public hospitals. The results in this paper
      suggest, perhaps surprisingly, that requiring private providers to serve the
      underinsured can be effective.

PMID- 21183235
TI  - Retirement effects on health in Europe.
AB  - What are the health impacts of retirement? As talk of raising retirement ages in
      pensions and social security schemes continues around the world, it is important
      to know both the costs and benefits for the individual, as well as the
      governments' budgets. In this paper we use the Survey of Health, Ageing and
      Retirement in Europe (SHARE) dataset to address this question in a multi-country
      setting. We use country-specific early and full retirement ages as instruments
      for retirement behavior. These statutory retirement ages clearly induce
      retirement, but are not related to an individual's health. Exploiting the
      discontinuities in retirement behavior across countries, we find significant
      evidence that retirement has a health-preserving effect on overall general
      health. Our estimates indicate that retirement leads to a 35 percent decrease in
      the probability of reporting to be in fair, bad, or very bad health, and an
      almost one standard deviation improvement in the health index. While the self
      reported health seems to be a temporary impact, the health index indicates there
      are long-lasting health differences.

PMID- 21183237
TI  - Comparison of the accuracy and precision of prostate localization with 2D-2D and
      3D images.
AB  - BACKGROUND AND PURPOSE: Positional uncertainties related to the set-up of the
      prostate, using internal markers and either 2D-2D or 3D images, were studied. Set
      up using direct prostate localization on CBCT scans is compared to set-up using
      internal markers. MATERIAL AND METHODS: 20 patients with prostate cancer were
      enrolled in the study. After each daily session, a set of 2D-2D and 3D images
      were acquired. The images isocenter was compared to reference images isocenter.
      For the set-up error analysis the systematic error, MU, and the set-up
      uncertainties, Sigma and sigma, were determined for the translational shift in
      the three directions, lat, lng and vrt. The set-up errors and uncertainties were
      calculated in the same way for rotations around the three axes, lat, lng and vrt.
      RESULTS: Set-up uncertainties were evaluated for four different set-up methods.
      The systematic error uncertainties were found to be in the range 0.38-1.14 mm and
      for the random error 0.79-1.48 mm. For rotations the uncertainties ranges were
      0.38-1.59 degrees  and 0.91-2.18 degrees  for systematic and random
      uncertainties, respectively. Set-up uncertainties, using internal markers or
      prostate itself to position the target in the isocenter, were comparable. The
      correlation between the two methods was better for translational shifts of the
      isocenter than for rotational shifts. CONCLUSIONS: The study shows that the
      precision of the 2D-2D set-up is equivalent to the precision of the 3D images. It
      also shows that the soft-tissue based set-up needs 1 mm larger set-up margins
      than the marker based set-up for the prostate patients, when CBCT is used for
      daily verification of the location of the prostate.

PMID- 21183238
TI  - Using RFLP-mtDNA for the rapid monitoring of the dominant inoculated yeast strain
      in industrial wine fermentations.
AB  - The analysis of restriction fragment length polymorphism of mitochondrial DNA
      (mtDNA-RFLP) has been applied as a test to monitor the abundance of the starter
      yeast strain during industrial wine fermentations without previous isolation of
      yeast colonies. For white wine fermentations, we performed a rapid assay
      consisting in taking a sample of fermenting must, purifying the DNA from
      harvested cells, and obtaining the restriction patterns by digestion with the
      endonuclease HinfI. The same protocol, but adding an overnight cultivation step
      before DNA purification, was also applied to red wine fermentations. The results
      were compared with those obtained from the subsequent characterisation of
      strains, for the same samples, by analysis of the electrophoretic karyotype of
      isolated yeast colonies. In all cases, when the inoculated strain was dominant
      within the yeast population, the rapid assay anticipated the result by showing
      the coincidence between the restriction profiles obtained from both total cells
      and the inoculated strain. The results were obtained at 11 or 23 h after sampling
      for white- or red-wine fermentations respectively. This method allows a rapid
      intervention of the wine-producer if the presence of the inoculated yeasts has
      suffered a sudden decrease in any phase of the fermentation process.

PMID- 21183239
TI  - Novel starter cultures to inhibit biogenic amines accumulation during fish sauce
      fermentation.
AB  - Bacteria with amine oxidase activity have become a particular interest to reduce
      biogenic amines concentration in food products such as meat and fish sausages.
      However, little information is available regarding the application of these
      bacteria in fish sauce. Hence, our study was aimed to investigate the effect of
      such starter cultures in reducing biogenic amines accumulation during fish sauce
      fermentation. Staphylococcus carnosus FS19 and Bacillus amyloliquefaciens FS05
      isolated from fish sauce which possess amine oxidase activity were used as
      starter cultures in this study. Fermentation was held for 120 days at 35  degrees
      C. The pH value increased in all samples, while salt concentration remained
      constant throughout fermentation. Aerobic bacteria count was significantly lower
      (p < 0.05) in the control than in inoculated samples as a result of starter
      cultures addition. However, it decreased during fermentation due to the growth
      inhibition by high salt concentration. Proteolytic bacterial count decreased
      during fermentation with no significant difference (p > 0.05) among samples.
      These bacteria hydrolyzed protein in anchovy to produce free amino acid
      precursors for amines formation by decarboxylase bacteria. The presence of
      biogenic amines producing bacteria in this study was considered to be indigenous
      from raw material or contamination during fermentation, since our cultures were
      negative histamine producers. Amino acid histidine, arginine, lysine and tyrosine
      concentration decreased at different rates during fermentation as they were
      converted into their respective amines. In general, biogenic amines concentration
      namely histamine, putrescine, cadaverine and tyramine increased throughout
      fermentation. However, their concentrations were markedly higher (p < 0.05) in
      the control (without starter cultures) as compared to the samples treated with
      starter cultures. Histamine concentration was reduced by 27.7% and 15.4% by
      Staphylococcus carnosus FS19 and Bacillus amyloliquefaciens FS05, respectively.
      Both cultures could also reduce other amines during fermentation. After 120 days
      of fermentation, the overall biogenic amines concentration was 15.9% and 12.5%
      less in samples inoculated with Staphylococcus carnosus FS19 and Bacillus
      amyloliquefaciens FS05, respectively, as compared to control samples. These
      findings emphasized that application of starter cultures with amines oxidase
      activity in fish sauce fermentation was found to be effective in reducing
      biogenic amines accumulation.

PMID- 21183240
TI  - Something's ironic in Denmark: an otherwise progressive welfare state lags well
      behind in care of patients at the end of life.
AB  - Tremendous strides have been made in the last two decades with regard to the
      quality of palliative care available to patients at the end of life. But progress
      has not been uniform, even among countries in the same region of the world. The
      objective of this study is to describe, in a comparative context, the current
      status of end-of-life palliative care in Denmark using quantitative research
      published in the past five years. This study's conclusions, based on a synthesis
      of the research, suggest that despite its well earned reputation as a generally
      progressive welfare state, Denmark tends to trail well behind its European
      neighbors when it comes to end-of-life care. Understanding the cultural forces
      that underlie this reality may help Danish health care professionals and policy
      makers overcome the barriers that stand in the way of providing state-of-the-art
      medical care to patients who suffer at the end of life.

PMID- 21183241
TI  - A finite element method approach for the mechanobiological modeling of the
      osseointegration of a dental implant.
AB  - The aim of this paper is to introduce a new mathematical model using a
      mechanobiological approach describing the process of osseointegration at the bone
      dental implant interface in terms of biological and mechanical factors and the
      implant surface. The model has been computationally implemented by using the
      finite element method. The results show the spatial-temporal patterns
      distribution at the bone-dental implant interface and demonstrate the ability of
      the model to reproduce features of the wound healing process such as blood
      clotting, osteogenic cell migration, granulation tissue formation, collagen-like
      matrix displacements and new osteoid formation. The model might be used as a
      methodological basis for designing a dental tool useful to predict the degree of
      osseointegration of dental implants and subsequent formulation of mathematical
      models associated with different types of bone injuries and different types of
      implantable devices.

PMID- 21183242
TI  - Dendritic cells matured by a prostaglandin E2-containing cocktail can produce
      high levels of IL-12p70 and are more mature and Th1-biased than dendritic cells
      treated with TNF-alpha or LPS.
AB  - Dendritic cells (DCs) play a crucial role in the initiation of an immune
      response. As maturation is critical for effective antigen presentation, different
      methods have been used to generate mature DCs (mDCs) ex vivo. The use of a
      maturation cocktail (MC) consisting of IL-1beta, IL-6, TNF-alpha, and
      prostaglandin E2 (PGE2) initially showed promising results, but then was
      challenged because of low production of IL-12p70 and the potential for induction
      of Th2-type immune responses. To investigate this contention, we compared two of
      the most commonly used maturation factors, TNF-alpha and LPS, with MC. Maturation
      cocktail was superior to TNF-alpha and LPS with respect to enhancement of mDC
      specific surface marker expression (CD83, CD86, and HLA-DR), induction of T cell
      proliferation by mDCs, and directional motility of mDCs toward CCL19. These
      results were supported by increased expression of a significant number of
      additional maturation-related genes by MC in comparison to TNF-alpha and LPS. In
      addition, we did not observe a Th2-biased shift in the gene expression profile of
      mDCs generated by MC. Conversely, MC induced more Th1-promoting transcriptional
      changes than LPS or TNF-alpha, including increased transcript levels of Th1-type
      cytokines such as IL-15, IL-12beta, and EBI3 (IL-27beta) and MHC class I
      molecules, Th1-promoting changes in the transcripts of CXCL16, CCL13, and CCL18,
      and reduced transcript levels of MHC class II molecules. More interestingly, the
      Th1-promoting characteristics of MC-mDCs were confirmed by their potential to
      produce large amounts of IL-12p70 after effective stimulation simulating in vivo
      events.

PMID- 21183243
TI  - Regions of recognition by blocking antibodies on the light chain of botulinum
      neurotoxin A: antigenic structure of the entire toxin.
AB  - The continuous regions on botulinum neurotoxin A (BoNT/A) light (L) chain
      recognized by anti-toxin antibodies (Abs) from mouse, horse and chicken have been
      mapped. We synthesized a panel of thirty-two 19-residue peptides that overlapped
      consecutively by 5 residues and encompassed the entire L chain (residues 1-453).
      Mouse Abs recognized 5 major antigenic regions on the L chain, horse Abs
      recognized 9 while chicken Abs recognized 8 major antigenic regions. Overall,
      however, the three host species recognized, to some extent, similar, but not
      identical, peptides and the levels of Abs directed against a given region varied
      with the immunized host. Differences in the MHC of the host caused variation in
      levels of Ab recognition and some epitopes showed right or left frame-shifts
      among the species. Selected region(s) were also uniquely recognized by one
      species (e.g., peptide L1 by horse Abs). Mapping of the L chain antigenic regions
      and the previous localization of the regions on the H chain with the same
      antisera, has permitted description of the complete antigenic structure of
      BoNT/A. The locations in the 3-dimensional structure of the antigenic regions of
      the entire toxin are shown for mouse Abs. In the 3-D structure, the antigenic
      regions are on the surface of the toxin and when antibodies are bound the
      enzymatic activity of the light chain is obstructed.

PMID- 21183244
TI  - [Tropical endemic limboconjunctivitis (vernal conjunctivitis) in northern
      Cameroon].
AB  - INTRODUCTION: A retrospective study was conducted in the ophthalmology unit of
      the Garoua regional hospital on children examined from January 2001 to December
      2007. We aimed to determine the epidemiological aspects of tropical endemic
      limboconjunctivitis in northern Cameroon. Included were all the files of patients
      aged 0-15 years seen with a positive diagnosis of tropical endemic
      limboconjunctivitis. The data analyzed were obtained through inspection,
      interview, and a comprehensive ocular exam done for every case, assessing far
      visual acuity, slit lamp biomicroscopy, and funduscopy when possible. The
      variables analyzed were age, sex, signs and symptoms, residential area,
      associated pathologies, and the month and the year of the diagnosis. The data
      were analyzed with Epi-Info, version 6.04d (French) and the results compared with
      the Chi(2) test with a 95% confidence interval. RESULTS: A total of 6453 children
      were included: 2036 had a positive diagnosis of tropical endemic
      limboconjunctivitis, with a frequency of 31.55%. The mean age was 6.5 years. The
      1- to 4-year-old age group had the highest number of patients, with a frequency
      of 33.25%. There were 1120 males (55%). Itching was the most frequent complaint
      encountered in 60.90% of the patients. Ocular involvement was always bilateral.
      Tropical endemic limboconjunctivitis is an allergic conjunctivitis present
      throughout the year with two peaks in March and July. DISCUSSION: Tropical
      endemic limboconjunctivitis can be considered an allergic conjunctivitis
      affecting boys more frequently than girls in warm and dry environments. It is
      frequent in children less than 5 years old and regresses with age. CONCLUSION:
      Tropical endemic limboconjunctivitis is a tropical disease with an intertropical
      aspect.

PMID- 21183245
TI  - [Medical and legal consequences of endophthalmitis].
AB  - Endophthalmitis is one of the leading sources of dispute in ophthalmology. The
      patient has a number of means to make an appeal. Fortunately, appeal to the
      criminal justice system is rare in medicine, but always possible (e.g.,
      indictment for endangering the life of others or for involuntary injury). Civil
      action is more frequent, allowing the patient to recover damages in case of
      negligence on the part of the surgeon. Finally, the law of March 4th 2002 allows
      the CRCI to award an indemnity to patients if the surgeon is not at fault, but in
      certain conditions only. The knowledge of the surgeon's obligations and the means
      of appeal available to the patient is very useful for the ophthalmologist.

PMID- 21183246
TI  - Use of the Internet by print medical journals in 2003 to 2009: a longitudinal
      observational study.
AB  - STUDY OBJECTIVE: To determine how a sample of medical journals use the Internet
      to provide additional content and features to readers and how this has changed
      since 2003. METHODS: In 2005, we surveyed 2003 and 2005 issues of 138 high-impact
      print medical journals to determine to what extent they were using the Internet
      to provide online-only articles and supplementary content to print articles
      (sampled 28 journals), and electronic space for the postpublication critique of
      their articles (sampled all 138 journals). We used the same methodology to
      determine what kinds of Web-only supplementary material were provided with each
      print article in March 2007 and 2009 issues of the same 28 journals used for the
      2003 to 2005 study. As before, we also determined which of the 138 journals
      offered rapid response pages and how those pages were being used. RESULTS: The
      proportion of the 28 journals providing Web-only supplementary material increased
      from 32% (2003) to 50% (2005) to 61% (2007) to 64% (2009), and the percentage of
      articles that contained supplementary material increased from 7% to 14% to 20% to
      25%, respectively. We observed a marked increase in the number of video
      supplements. In contrast, journals offering online postpublication review
      decreased from 17 of 138 (12%) to 12 of 138 (9%) to 11 of 138 (8%) from 2005 to
      2007 to 2009, and the percentage of articles with no responses was unchanged at
      82%. CONCLUSION: The use of online-only articles and online-only supplements by
      print journals continues to increase. Postpublication critique of articles in
      online pages provided by the journal does not seem to be taking hold.

PMID- 21183247
TI  - Not preventing falls--promoting function.

PMID- 21183248
TI  - The spirit of collaboration and supervision.

PMID- 21183249
TI  - [Study on the clinicopathological correlation in the secondary acute respiratory
      distress syndrome].
AB  - OBJECTIVE: This study has aimed to study the clinicopathological correlation of
      patients with secondary acute respiratory distress syndrome (ARDS), specifically
      having extrapulmonary causes. SETTING: A 22 beds intensive care unit. DESIGN: An
      observational study of case series. PATIENTS: Seventeen patients whose death was
      caused by acute respiratory distress syndrome were included. INTERVENTION: A
      systematic histopathological study was made of all the pulmonary lobes of
      patients who died in our ICU with the clinical diagnosis of secondary ARDS, who
      had undergone an autopsy between 1999 and 2009. The Kappa analysis was used to
      analyze the grade of correlation between the clinical and the pathological
      diagnosis. RESULTS: The autopsy confirmed to cases of false positive in 17
      patients with ARDS (11%). The kappa value was 0.77, so that the concordance
      analysis was considered to be satisfactory. CONCLUSIONS: The clinical criteria
      for ARDS correlate well with acute alveolar damage (AAD) in the autopsy study in
      patients with secondary ARDS, although some false positive cases can be observed.

PMID- 21183250
TI  - [Heart failure patients in Primary Care: aging, comorbidities and polypharmacy].
AB  - OBJECTIVE: To assess heart failure prevalence, epidemiology, co-morbidities and
      polypharmacy in our region from electronic patient records. To evaluate gender
      differences in heart failure patients. DESIGN: Descriptive, cross-sectional
      study. SETTING: Primary care Lleida (Spain). PARTICIPANTS: All patients from 21
      primary care centers with the diagnosis of heart failure in medical records were
      included. MAIN OUTCOME MEASUREMENTS: Demographic data, comorbidities and
      therapeutical subgroups in patients with a diagnosis of heart failure in their
      clinical record. RESULTS: Heart failure was found in 0.99% (3017 from 306229
      patients), of whom 59% were women, and a mean age of 80 years. Comorbidities:
      hypertension 67%, diabetes 30%, hyperlipidemia 26.5%, obesity 27%, ischemic heart
      disease 19%, stroke 11%, atrial fibrillation 31%, COPD 26%, renal failure 12%.
      Hypertension, hyperlipidemia and obesity were more frequent in women, COPD,
      ischemic heart disease and renal failure in men. There were no differences in
      diabetes, stroke and atrial fibrillation. Patients were prescribed a median of 8
      different therapeutic subgroups (P25=6 and P75=11). Women were more frequently
      prescribed diuretics (76%), cardiac glycosides (22%) and ACE
      inhibitors/angiotensin II receptor antagonists, and men ACE
      inhibitors/angiotensin II receptor antagonists in combination with beta-blockers.
      CONCLUSIONS: Heart failure patients in primary care are elderly, with significant
      co-morbidities and treated with a high number of drugs. Gender differences exist
      in cardiovascular risk factors, co-morbidities, and also in therapy.

PMID- 21183251
TI  - [Evidence-based disinvestment in Spain].

PMID- 21183252
TI  - [From the chronic disease to the patient in a chronic condition].

PMID- 21183253
TI  - [Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC)
      guidelines for the diagnosis of invasive fungal infections. 2010 update].
AB  - These guidelines are an update of recommendations for the diagnosis of invasive
      fungal infections by the Spanish Society of Clinical Microbiology and Infectious
      Diseases (SEIMC) published in 2004 (Enferm Infecc Microbiol Clin. 2004, 22:32-9).
      In this updated version of the guidelines, a comprehensive review of the most
      recent diagnostic innovations and levels of evidence to recommend those
      diagnostic procedures are included. We first analyse conventional diagnostic
      methods, microscopic examination and culture, underlining their limitations which
      have led to the development of alternative methods, such as fungal antigen and
      DNA quantification. Those alternative methods of diagnosis are analysed by fungal
      infection. We also briefly review the methods for molecular identification of
      fungal species and recommendations for carrying out susceptibility tests for
      antifungal drugs, including reference procedures, commercial techniques and their
      indications.

PMID- 21183254
TI  - [Children with cancer and respiratory viral infection: epidemiology, diagnosis
      and treatment options].
AB  - Community-adquired respiratory viral infection is the most common cause of
      febrile infection in children, and an important cause of infection to consider in
      children with cancer. Nevertheless, there are few well-designed, controlled
      studies in this population, which makes it difficult to understand the
      importance, behaviour and management of these viruses in immunocompromised
      children. New diagnostic techniques in PCR-based microbiology, could provide many
      opportunities for early diagnosis, preventing the spread of the virus and to
      implement the correct therapy. It is important to design appropriate prospective
      studies to assess these types of infections in children with cancer. In this
      review we analyse the main studies published in the literature, evaluating the
      epidemiology, diagnosis and management of children with cancer and respiratory
      viral infection.

PMID- 21183256
TI  - Peripheral neuropathy as a first sign of microscopic polyangiitis.

PMID- 21183257
TI  - Three-dimensional quantitative structure-selectivity relationships analysis
      guided rational design of a highly selective ligand for the cannabinoid receptor
      2.
AB  - This paper describes a three-dimensional quantitative structure-selectivity
      relationships (3D-QSSR) study for selectivity of a series of ligands for
      cannabinoid CB1 and CB2 receptors. 3D-QSSR exploration was expected to provide
      design information for drugs with high selectivity toward the CB2 receptor. The
      proposed 3D computational model was performed by Phase and generated taking into
      account a number of structurally diverse compounds characterized by a wide range
      of selectivity index values. The model proved to be predictive, with r2 of 0.95
      and Q2 of 0.63. In order to get prospective experimental validation, the
      selectivity of an external data set of 39 compounds reported in the literature
      was predicted. The correlation coefficient (r2=0.56) obtained on this unrelated
      test set provided evidence that the correlation shown by the model was not a
      chance result. Subsequently, we essayed the ability of our approach to help the
      design of new CB2-selective ligands. Accordingly, based on our interest in
      studying the cannabinergic properties of quinolones, the N-(adamantan-1-yl)-4-oxo
      8-methyl-1-pentyl-1,4-dihydroquinoline-3-carboxamide (65) was considered as a
      potential synthetic target. The log(SI) value predicted by using our model was
      indicative of high CB2 selectivity for such a compound, thus spurring us to
      synthesize it and to evaluate its CB1 and CB2 receptor affinity. Compound 65 was
      found to be an extremely selective CB2 ligand as it displayed high CB2 affinity
      (Ki=4.9 nM), while being devoid of CB1 affinity (Ki>10,000 nM). The
      identification of a new selective CB2 receptor ligand lends support for the
      practicability of quantitative ligand-based selectivity models for cannabinoid
      receptors. These drug discovery tools might represent a valuable complementary
      approach to docking studies performed on homology models of the receptors.

PMID- 21183258
TI  - Synthesis and effects of some novel tetrahydronaphthalene derivatives on
      proliferation and nitric oxide production in lipopolysaccharide activated Raw
      264.7 macrophages.
AB  - In this study, novel N-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalene-2-yl)
      carboxamide (6-15) and 5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2
      carboxamide (16-32) derivatives were synthesized and their in vitro effects at 5
      MUM and 50 MUM concentrations on proliferation and nitric oxide (NO*) production
      in lipopolysaccharide (LPS) activated RAW 264.7 macrophage cells were determined.
      Compounds 12, 17, 24 and 26 were found to decrease nitrite levels in a dose
      dependent manner in LPS-activated cells. At the tested concentrations, these
      compounds did not exhibit cytotoxic effects. Interestingly, compound 27 which
      contains nitroxide free radical was the most active compound in this series
      showing 59.2% nitrite inhibition in LPS-activated macrophage cells.

PMID- 21183259
TI  - Synthesis of 2-(aminomethyl)aziridines and their microwave-assisted ring opening
      to 1,2,3-triaminopropanes as novel antimalarial pharmacophores.
AB  - A variety of 2-(aminomethyl)aziridines was prepared and converted into the
      corresponding 1,2,3-triaminopropanes through a novel, microwave-assisted and
      regioselective ring opening by diethylamine in acetonitrile. Antiplasmodial
      assays revealed antimalarial activity for 2-[(1,2,4-triazol-1
      yl)methyl]aziridines and 2-(N,N-diethylaminomethyl)aziridines, as well as for the
      corresponding 1-(diethylamino)propanes obtained through ring opening, pointing to
      the relevance of both the 2-(aminomethyl)aziridine and the 1,2,3-triaminopropane
      unit as novel antimalarial pharmacophores.

PMID- 21183260
TI  - Diurnal variation in stature: do those with chronic low-back pain differ from
      asymptomatic controls?
AB  - BACKGROUND: Stature loss is a commonly used measure of spinal load. The aim of
      this study was to investigate the pattern of diurnal stature change in those with
      and without chronic low-back pain, over a 24-h period. METHODS: Eight
      participants with chronic low-back pain (age 24.6 (SD 4.3) years, height 1.76 (SD
      0.08) m, body mass 72.8 (SD 11.1) kg) and eight controls (age 21.8 (SD 2.0)
      years, height 1.75 (SD 0.10) m, body mass 71.8 (SD 11.6) kg) participated in this
      investigation. Twenty-four stature measurements were performed over a 24-h
      period. FINDINGS: The trough to peak variation in stature of 17.9 mm (low-back
      pain group) and 17.6mm (control group) did not differ between groups (P>0.05).
      Both groups experienced greatest stature change in the 1st hour after rising
      (31.3% [low-back pain] and 44.6% [control] of total stature change). At
      approximately 18:00h the LBP group reached a plateau whilst the control group
      continued to lose stature. Between 14:00 and 18:00h both groups demonstrated a
      previously unreported recovery of stature. A significant correlation was found
      between low-back discomfort and stature change in the low-back pain group only.
      INTERPRETATION: No significant difference existed between groups in relation to
      total stature loss; however the low-back pain group appeared to reach their nadir
      earlier, possibly exposing other spinal structures to loading for a greater
      duration. This is supported by the relationship found between stature loss and
      discomfort. The reversal in stature loss in the afternoon may be of clinical
      significance and warrants further investigation.

PMID- 21183261
TI  - The formation of bound residues of diazinon in four UK soils: implications for
      risk assessment.
AB  - The behaviour of diazinon in the soil determines the likelihood of further
      pollution incidents, particularly leaching to water. The most significant
      processes in the control of the fate of diazinon in the soil are microbial
      degradation and the formation of bound residues. Soils from four sites in the UK
      were amended with diazinon and its (14)C labelled analogue and incubated for 100
      days. After 0, 10, 21, 50 and 100 days, the formation of bound residues was
      assessed by solvent extraction, and the microbial degradation of diazinon by
      mineralisation assay. In microbially active soils, diazinon is degraded rapidly,
      reducing the risk of future pollution incidents. However, where there was limited
      mineralisation there was also significantly lower formation of bound residues,
      which may lead to water pollution via leaching. The formation of bound residues
      was dependent on extraction type. Acetonitrile extraction identified bound
      residues in all soils, with the bound residue fraction increasing with increasing
      incubation time.

PMID- 21183262
TI  - Behavior of decabromodiphenyl ether (BDE-209) in soil: effects of rhizosphere and
      mycorrhizal colonization of ryegrass roots.
AB  - A rhizobox experiment was conducted to investigate degradation of
      decabromodiphenyl ether (BDE-209) in the rhizosphere of ryegrass and the
      influence of root colonization with an arbuscular mycorrhizal (AM) fungus. BDE
      209 dissipation in soil varied with its proximity to the roots and was enhanced
      by AM inoculation. A negative correlation (P < 0.001, R(2) = 0.66) was found
      between the residual BDE-209 concentration in soil and soil microbial biomass
      estimated as the total phospholipid fatty acids, suggesting a contribution of
      microbial degradation to BDE-209 dissipation. Twelve and twenty-four lower
      brominated PBDEs were detected in soil and plant samples, respectively, with a
      higher proportion of di- through hepta-BDE congeners in the plant tissues than in
      the soils, indicating the occurrence of BDE-209 debromination in the soil-plant
      system. AM inoculation increased the levels of lower brominated PBDEs in
      ryegrass. These results provide important information about the behavior of BDE
      209 in the soil-plant system.

PMID- 21183263
TI  - Pedogenesis, geochemical forms of heavy metals, and artifact weathering in an
      urban soil chronosequence, Detroit, Michigan.
AB  - An urban soil chronosequence in downtown Detroit, MI was studied to determine the
      effects of time on pedogenesis and heavy metal sequestration. The soils developed
      in fill derived from mixed sandy and clayey diamicton parent materials on a level
      late Pleistocene lakebed plain under grass vegetation in a humid-temperate
      (mesic) climate. The chronosequence is comprised of soils in vacant lots (12 and
      44 years old) and parks (96 and 120 years old), all located within 100 m of a
      roadway. An A-horizon 16 cm thick with 2% organic matter has developed after only
      12 years of pedogenesis. The 12 year-old soil shows accelerated weathering of
      iron (e.g. nails) and cement artifacts attributed to corrosion by excess soluble
      salts of uncertain origin. Carbonate and Fe-oxide are immobilizing agents for
      heavy metals, hence it is recommended that drywall, plaster, cement and iron
      artifacts be left in soils at brownfield sites for their ameliorating effects.

PMID- 21183264
TI  - Substance misuse and substance use disorders in sex offenders: a review.
AB  - Substance abuse has often been associated with committing sex offenses. In this
      article, the following will be reviewed: 1) studies that assessed substance abuse
      in sex offenders; 2) differences in substance abuse among different types of sex
      offenders; 3) differences in substance abuse between sex offenders and nonsexual
      offenders and substance abuse in the normal population; 4) sex offenders'
      intoxication at the time of the offense; and 5) differences in intoxication at
      the time of the offense among different types of sex offenders. Studies will be
      discussed according to the method they used to assess substance abuse, i.e., file
      research, screening instruments or semi-structured interviews. This review shows
      that about half of the sex offenders has a history of substance abuse, a quarter
      to half of the sex offenders has a history of alcohol misuse and that about one
      fifth to a quarter of the sex offenders has a history of drug misuse.
      Furthermore, about a quarter to half of the sex offenders appeared to be
      intoxicated at the time of the offense. The review results in recommendations for
      future research. Because of the high prevalence of substance abuse in sex
      offenders it is advisable to routinely screen for substance abuse and, if
      necessary, to treat substance abuse.

PMID- 21183265
TI  - Does mindfulness training improve cognitive abilities? A systematic review of
      neuropsychological findings.
AB  - Mindfulness meditation practices (MMPs) are a subgroup of meditation practices
      which are receiving growing attention. The present paper reviews current evidence
      about the effects of MMPs on objective measures of cognitive functions. Five
      databases were searched. Twenty three studies providing measures of attention,
      memory, executive functions and further miscellaneous measures of cognition were
      included. Fifteen were controlled or randomized controlled studies and 8 were
      case-control studies. Overall, reviewed studies suggested that early phases of
      mindfulness training, which are more concerned with the development of focused
      attention, could be associated with significant improvements in selective and
      executive attention whereas the following phases, which are characterized by an
      open monitoring of internal and external stimuli, could be mainly associated with
      improved unfocused sustained attention abilities. Additionally, MMPs could
      enhance working memory capacity and some executive functions. However, many of
      the included studies show methodological limitations and negative results have
      been reported as well, plausibly reflecting differences in study design, study
      duration and patients' populations. Accordingly, even though findings here
      reviewed provided preliminary evidence suggesting that MMPs could enhance
      cognitive functions, available evidence should be considered with caution and
      further high quality studies investigating more standardized mindfulness
      meditation programs are needed.

PMID- 21183266
TI  - Professional relations in sport healthcare: workplace responses to organisational
      change.
AB  - This article examines the impact of organisational changes in UK elite sport on
      the professional relations among and between different healthcare providers. The
      article describes the processes by which demand for elite sport healthcare has
      increased in the UK. It further charts the subsequent response within medicine
      and physiotherapy and, in particular, the institutionalisation of sport-specific
      sub-disciplines through the introduction of specialist qualifications. Drawing on
      semi-structured interviews with 14 doctors and 14 physiotherapists, the article
      argues that organisational changes have led to intra-professional tensions within
      both professional groups but in qualitatively different forms reflecting the
      organisational traditions and professional identities of the respective
      disciplines. Organisational changes promoting multi-disciplinary healthcare teams
      have also fostered an environment conducive to high levels of inter-professional
      cooperation though significant elements of inter-professional conflict remain.
      This study illustrates how intra-professional relations are affected by
      specialisation, how legitimation discourses are used by different professions,
      and how intra- and inter-professional conflict and cooperation should be seen as
      highly interdependent processes.

PMID- 21183267
TI  - Job loss and depression: the role of subjective expectations.
AB  - Although the importance of expectations is well documented in the decision-making
      literature, a key shortcoming of the empirical research into effects of
      involuntary job loss on depression is perhaps its neglect of the subjective
      expectations of job loss. Using data from the US Health and Retirement Study
      surveys we examine whether the impact of job loss on mental health is influenced
      by an individual's subjective expectations regarding future displacement. Our
      results imply that, among older workers in the age range of 55-65 year,
      subjective expectations are as significant predictors of depression as job loss
      itself, and ignoring them can bias the estimate of the impact of job loss on
      mental health.

PMID- 21183268
TI  - Placental pathology in fetal growth restriction.
AB  - OBJECTIVES: One of the causes of intrauterine fetal growth restriction (FGR) can
      be pathology of the placenta. The aim of this study was to compare macroscopic
      and microscopic changes of the placentas from intrauterine growth restricted
      fetuses with those from normally developed fetuses, in order to test the
      hypothesis that vascular damage due to decreased maternal vascular perfusion may
      be responsible for FGR. STUDY DESIGN: Between May 2007 and December 2008 we
      performed detailed macroscopic and histological examination of singleton
      placentas of 50 consecutive neonates with fetal growth restriction (FGR group)
      and compared them to 50 normal fetuses, born next to an FGR case, as a control
      group. RESULTS: Gestational age, birth weight, spontaneous delivery rate, mean
      weight of the placenta and the fetal-placental weight ratio were all lower in the
      FGR group than in the control group (p<0.05). Thickening of the villous
      trophoblastic basal membrane, incidence of villous infarction, presence of
      thrombi or haematomas and the incidence of villitis were more common in the FGR
      group than in the controls (p<0.05). There were, however, no significant
      differences in perivillous fibrin deposition, stromal fibrosis and
      cytotrophoblast proliferation between the groups. In FGR women who smoked,
      intervillous haematomas and villous infarction were more common (p<0.05) than in
      controls. CONCLUSIONS: All macroscopic and microscopic pathological changes
      associated with FGR were directly linked to reduction of placental blood flow. As
      smoking is a main risk factor for these placental abnormalities these results
      emphasize the need to persuade women to quit smoking not only during pregnancy,
      but even better long before pregnancy.

PMID- 21183269
TI  - Pregnancy after renal transplantation: an evaluation of the graft function.
AB  - OBJECTIVES: To evaluate pregnancy outcomes and graft function in renal transplant
      recipients. STUDY DESIGN: Thirty-four pregnancies in 31 patients were evaluated.
      Graft dysfunction was defined as an increase of 0.3mg/dL (215 MUmol/L) or more in
      serum creatinine (SCr) during pregnancy. Twenty-eight patients were also
      evaluated at one, six and twelve months after delivery to analyze the evolution
      of the graft function. RESULTS: Fifteen patients experienced graft dysfunction
      during pregnancy, 10 related to preeclampsia, two related to rejection, one
      related to allograft obstruction and one related to urinary tract infection. One
      patient did not have an identified cause. In one patient, graft rejection ended
      in graft loss. The mean SCr level in the first trimester was 0.9 mg/dL (range:
      0.5-2.1) among women who did not have graft dysfunction and 1.1mg/dL (range: 0.5
      1.9) among patients who had graft dysfunction (P=0.66). The mean SCr level one
      year after delivery was 1.18 mg/dL in the first group and 1.21 mg/dL in the
      second group (P=0.74). There was no difference in SCr level from the first
      trimester of pregnancy to one year after delivery in both groups evaluated
      (P=0.35 and P=0.13). CONCLUSIONS: Although graft dysfunction may occur during
      pregnancy, it seems to be temporary in the majority of the cases. It is important
      to emphasize that rejection is still a cause of graft loss during pregnancy.

PMID- 21183270
TI  - Funisitis is associated with increased interleukin-10 gene expression in cord
      blood mononuclear cells in preterm infants <=32 weeks of gestation.
AB  - OBJECTIVES: A systemic inflammatory response after intrauterine funisitis is
      assumed to be an important priming factor for acute and chronic pulmonary
      morbidity and neurological impairment in premature infants. Fetal lymphocytes and
      monocytes modulate the primary immune response. Genetic regulation of the
      cytokine-mediated process is partially known. The objective of our study was to
      examine the pro-inflammatory and anti-inflammatory responses in umbilical cord
      blood mononuclear cells (CBMC) of preterm infants on the transcriptional level.
      STUDY DESIGN: Fifteen preterm infants with a gestational age <=32 weeks were
      enrolled in this prospective study. Funisitis was diagnosed in five of the 15 by
      histological examination. Gene expression of pro-inflammatory cytokines (TNF
      alpha, IL-8, IL-1beta and IL-17) and anti-inflammatory cytokines (IL-10 and TGF
      beta1) was examined in CBMC by real time reverse transcription polymerase chain
      reaction. RESULTS: Gene expression of IL-10 was significantly higher in the
      funisitis group compared to unexposed controls (p<0.008). Expression of TGF
      beta1, TNF-alpha, IL-8 and IL-1beta did not differ significantly between the
      funisitis and control group. IL-17 was detectable in only two samples.
      CONCLUSIONS: Funisitis is associated with increased IL-10 gene expression in CBMC
      of preterm infants with a gestational age <=32 weeks. This might contribute to
      modulation of postnatal immunoreactions and immunoregulation in these
      individuals.

PMID- 21183271
TI  - Study of the Alzheimer's Abeta40 peptide in SDS micelles using molecular dynamics
      simulations.
AB  - The interaction of the Alzheimer's amyloid beta peptide, Abeta40, with sodium
      dodecyl sulfate (SDS) micelles, together with the self-assembly of SDS molecules
      around the peptide from an initial random distribution were studied using
      atomistic and coarse-grained (CG) molecular dynamics simulations. In atomistic
      simulations, the peptide structure in the micelle was characterized by two
      helical regions connected through a short hinge. The initial structure of the
      system was shown to affect the simulation results. The atomistic self-assembly of
      SDS molecules resulted in a 38-molecule micelle around the peptide, along with
      some globules and individual molecules. Coarse-grained simulation results,
      however, did not show such a difference, and at the end of all CG simulations, a
      complete 60-molecule micelle was obtained, with the peptide located at the
      interface of the micelle with water. The obtained CG radial density profiles and
      SDS micelle size and shape properties were identical for all CG simulations.

PMID- 21183272
TI  - Metal contamination in sediments of the western Bohai Bay and adjacent estuaries,
      China.
AB  - Twelve sediment cores were collected in July 2007 in open waters of western Bohai
      Bay, the Port of Tianjin, and the adjacent estuaries of the Haihe and Yongding
      Rivers. While overall concentrations of trace metals at incremental depths in
      these cores met the Marine Sediment Quality (GB18668-2002) criteria of China, the
      magnitude of both metal enrichment factors (EF) and geoaccumulation indices
      (I(geo)) suggested that pollution with Ag, Cd, Cr, Cu and Zn was occurring in the
      estuaries and Port. Risk analysis also suggested that Ag and Ni concentrations
      were sufficiently elevated as to cause adverse biological effects in the study
      area. Although metal concentrations in western Bohai Bay were of less concern, a
      positive relationship between EF values and excess (210)Pb activity for several
      metals suggested that their concentrations were increasing over time.

PMID- 21183273
TI  - Co-digestion of pig manure and glycerine: experimental and modelling study.
AB  - It is a fact that the rapid increase of biodiesel production over the last years
      has resulted in the generation of large and constant amounts of glycerine, which
      is causing an oversupply problem. Since glycerine is a biodegradable organic
      compound exempt of nitrogen, it can be applied as a co-substrate in the anaerobic
      digestion process of pig manure (PM). In order to analyze the feasibility of a
      mixture of pig manure and glycerine in anaerobic processes and to define the
      effect originated by the nitrogen limitation when large amounts of glycerine are
      added, several biodegradability batch tests were performed with different
      mixtures. These were named as: 100% PM, 80% PM, 60% PM, 40% PM and 20% PM, in pig
      manure wet weight-basis. Furthermore, a modified model based on anaerobic
      digestion model no.1 (ADM1) was used to simulate the methane production profiles
      for the mixtures tested. Specifically, both experimental and model results show
      the power of the co-digestion technology. In particular, the mixture of 80% PM
      produced the highest methane production with 215 mL CH(4) g(-1) COD, almost 125%
      more methane than when pig manure was mono-digested. In contrast, the one with
      20% PM was clearly inhibited by the volatile fatty acid due to the low nitrogen
      concentration of the mixture. In addition, the specific methane production
      predicted by the model was in good agreement with the experimental results,
      although in some samples the shape of the profiles did not match perfectly.
      Moreover, the modified ADM1 appears to be a useful tool to predict the methane
      production and the limitations related to the lack/excess of nitrogen during the
      co-digestion process of pig manure and glycerine.

PMID- 21183275
TI  - Thyroid hormone as a regulator of tumor induced angiogenesis.
AB  - Thyroid hormones (TH) - 3,5,3'-triiodo-L-thyronine (T3) and l-thyroxine (T4) -
      are important regulators of differentiation, growth, metabolism, and
      physiological function in most tissues. TH have been also implicated in cellular
      transformation, tumorigenesis and metastasis, assuming particular importance in
      tumor induced angiogenesis. TH-induced angiogenesis is thought to be initiated at
      integrin alphavbeta3 membrane receptor mainly through T4 binding. The reduction
      of TH in circulation or the inhibition of TH actions at the integrin alphavbeta3
      receptor would consequently produce a reduction on the proliferative and
      angiogenic TH effects. Therefore, targeting TH actions could be an alternative
      adjuvant therapy against cancer proliferation and angiogenesis.

PMID- 21183274
TI  - Heterozygous exon 3 deletion in the Parkin gene in a patient with clinical and
      radiological MSA-C phenotype.

PMID- 21183276
TI  - Application of experimental design approach and artificial neural network (ANN)
      for the determination of potential micellar-enhanced ultrafiltration process.
AB  - In this study, micellar-enhanced ultrafiltration (MEUF) was applied to remove
      zinc ions from wastewater efficiently. Frequently, experimental design and
      artificial neural networks (ANNs) have been successfully used in membrane
      filtration process in recent years. In the present work, prediction of the
      permeate flux and rejection of metal ions by MEUF was tested, using design of
      experiment (DOE) and ANN models. In order to reach the goal of determining all
      the influential factors and their mutual effect on the overall performance the
      fractional factorial design has been used. The results show that due to the
      complexity in generalization of the MEUF process by any mathematical model, the
      neural network proves to be a very promising method in compared with fractional
      factorial design for the purpose of process simulation. These mathematical models
      are found to be reliable and predictive tools with an excellent accuracy, because
      their AARE was +/-0.229%, +/-0.017%, in comparison with experimental values for
      permeate flux and rejection, respectively.

PMID- 21183277
TI  - Vaccination of chickens with DNA vaccine expressing Eimeria tenella MZ5-7 against
      coccidiosis.
AB  - A chimeric DNA vaccine co-expressing Eimeria tenella MZ5-7 and chicken IL-17 gene
      was constructed and its efficacy against E. tenella challenge was evaluated. The
      ORF of MZ5-7 from E. tenella's second generation merozoite and the mature
      interleukin 17 gene of chicken were cloned into the expression vector of pcDNA4.0
      to construct DNA vaccine pcDNA4.0-MZ and pcDNA4.0-MZ-IL17. The expression of aim
      gene products in vivo was detected by western blotting. The expression of IL-2
      and IFN-gamma in chicken splenocytes was detected by RT-PCR 7 days post
      immunization. The expression levels of the two cytokines in the pcDNA4.0-MZ-IL17
      DNA vaccine immunized group were significantly higher than that in the pcDNA4.0
      MZ immunized group (p<0.05). Either pcDNA4.0-MZ or pcDNA4.0-MZ-IL17 DNA vaccine
      could obviously alleviate cecal lesions, body weight loss and increase oocyst
      decrease ratio. The ACI of pcDNA4.0-MZ-IL17 group was 190, which is higher than
      that of pcDNA4.0-MZ group and all the three control groups. In short, MZ5-7 was
      an effective candidate antigen for vaccine and co-expression of cytokine with
      antigen was an alternative method to enhance the immunity DNA vaccine.

PMID- 21183278
TI  - Prevalence and genotypes of Toxoplasma gondii in feline faeces (oocysts) and meat
      from sheep, cattle and pigs in Switzerland.
AB  - The protozoan parasite Toxoplasma gondii infects almost all warm blooded animal
      species including humans, and is one of the most prevalent zoonotic parasites
      worldwide. Post-natal infection in humans is acquired through oral uptake of
      sporulated T. gondii oocysts or by ingestion of parasite tissue cysts upon
      consumption of raw or undercooked meat. This study was undertaken to determine
      the prevalence of oocyst-shedding by cats and to assess the level of infection
      with T. gondii in meat-producing animals in Switzerland via detection of genomic
      DNA (gDNA) in muscle samples. In total, 252 cats (44 stray cats, 171 pet cats, 37
      cats with gastrointestinal disorders) were analysed coproscopically, and
      subsequently species-specific identification of T. gondii oocysts was achieved by
      Polymerase Chain Reaction (PCR). Furthermore, diaphragm samples of 270 domestic
      pigs (120 adults, 50 finishing, and 100 free-range animals), 150 wild boar, 250
      sheep (150 adults and 100 lambs) and 406 cattle (47 calves, 129 heifers, 100
      bulls, and 130 adult cows) were investigated by T. gondii-specific real-time PCR.
      For the first time in Switzerland, PCR-positive samples were subsequently
      genotyped using nine PCR-restriction fragment length polymorphism (PCR-RFLP) loci
      (SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico) for analysis. Only
      one of the cats shed T. gondii oocysts, corresponding to a T. gondii prevalence
      of 0.4% (95% CI: 0.0-2.2%). In meat-producing animals, gDNA prevalence was lowest
      in wild boar (0.7%; 95% CI: 0.0-3.7%), followed by sheep (2.0%; 95% CI: 0.1-4.6%)
      and pigs (2.2%; 95% CI: 0.8-4.8%). The highest prevalence was found in cattle
      (4.7%; 95% CI: 2.8-7.2%), mainly due to the high prevalence of 29.8% in young
      calves. With regard to housing conditions, conventional fattening pigs and free
      range pigs surprisingly exhibited the same prevalence (2.0%; 95% CI: 0.2-7.0%).
      Genotyping of oocysts shed by the cat showed T. gondii with clonal Type II
      alleles and the Apico I allele. T. gondii with clonal Type II alleles were also
      predominantly observed in sheep, while T. gondii with mixed or atypical allele
      combinations were very rare in sheep. In pigs and cattle however, genotyping of
      T. gondii was often incomplete. These findings suggested that cattle in
      Switzerland might be infected with Toxoplasma of the clonal Types I or III,
      atypical T. gondii or more than one clonal Type.

PMID- 21183279
TI  - Administration of a long-acting antiparasitic to pre-pubertal ewe-lambs in Greece
      results in earlier reproductive activity and improved reproductive performance.
AB  - We studied the reproductive effects of administration of a long-acting
      antiparasitic (moxidectin) given to pre-pubertal ewe-lambs in Greece at the
      beginning of the reproductive season. 45 animals, naturally infected with
      trichostrongylids, were allocated into treated (n=30, treatment on D0, 21 June)
      or control (n=15) group. Rams of confirmed fertility, were introduced from 15
      August (D55) to 20 December (D182) into the ewe-lambs. Throughout the study
      (performed at latitude N 36 degrees 26', in a flock free from brucellosis,
      Chlamydophila infection and toxoplasmosis), epg counts were monitored and
      reproductive performance of ewes was assessed. Up to D112, arithmetic mean epg
      counts in treated animals were 0; thereafter and up to D350, they were 23-473.
      Respective figures for controls were 190-977 epg. Reproductive performance
      parameters for treated and control animals respectively, were as follows; median
      'Interval to first mating after ram introduction': 36.5 d and 71.0 (P=0.04);
      median 'Age at first mating': 8.5m and 10.0m (P=0.045); 'Cycling rate': 20.0% and
      6.7% (P=0.03); 'Mating rate': 86.7% and 66.7%; 'Return-to-oestrus rate': 26.7%
      and 26.7%; 'Abortion rate': 3.3% and 0%; 'Lambing rate': 83.3% and 66.7%; 'Total
      lambs born per ewe' and 'Liveborn lambs born per ewe': 1.5 and 1.1 (P=0.01);
      'Stillbirth rate' 0% and 0% and 'Lamb bodyweight per ewe': 5.0 kg and 3.8 kg
      (P=0.005). Anthelmintic treatment of pre-pubertal ewes, in order to maximise
      reproductive performance may be employed as a management strategy according to
      targets set in individual flocks.

PMID- 21183280
TI  - Comparable results of epidemiology of children with burns among different decades
      in a burn unit in JinZhou, China.
AB  - OBJECTIVE: The aim of this study was to compare the epidemiological results of
      children with burns among different decades from 1970 to 2008. METHODS: The
      clinical data of all children with burns younger than 14 years admitted between
      1970 and 2008 were compared among different decades using Statistical Package for
      Social Sciences (SPSS). RESULTS: Of all patients with burns, children accounted
      for 28.6%, despite differences in different decades (18.7-31%). In all children
      with burns, greater than 80% were accounted by children with mild and moderate
      burns, and by scalds, in which greater than 80% was caused by hot water. The
      proportion of scald gradually increased from 60% in the 1970s to 88% in 21st
      century. The increase in the number in the infant group was the direct cause for
      the decline of the average age of children injured over time. The case fatality
      rate in all children with burns was 0.7%, despite significant differences in
      different decades. CONCLUSION: Current prevention strategies should be aimed at
      the 'susceptible group', namely infants, scald injuries and hot water scald, in
      particular, according to the epidemiologic characteristics of this study.
      Prevention methods from government, mass media and schools to the family is a
      tremendous need for the further development of prevention of paediatric burns in
      the future.

PMID- 21183281
TI  - Targeted epidermal growth factor receptor therapy in malignant pleural
      mesothelioma: where do we stand?
AB  - The median survival for patients with malignant pleural mesothelioma remains
      extremely poor and there is a need for the development of more effective
      treatment modalities. The epidermal growth factor receptor is frequently over
      expressed in malignant pleural mesothelioma samples and therefore may be a
      potential therapeutic target. Targeted EGFR therapy has been successful in non
      small cell lung cancer using small molecule tyrosine kinase inhibitors and in
      colorectal cancer using monoclonal anti-EGFR antibodies. However, phase II
      clinical trials based on EGFR tyrosine kinase inhibitor therapy have so far not
      shown promise in mesothelioma. This review includes a background to targeted EGFR
      treatment strategies, explores putative therapy resistance mechanisms, including
      the role of predictive biomarkers, and describes the current status of targeted
      EGFR therapeutic strategies for mesothelioma patients.

PMID- 21183282
TI  - Rituximab in Hodgkin lymphoma: is the target always a hit?
AB  - In 1997, the anti-CD20 monoclonal antibody (MAb) rituximab became the first MAb
      approved for clinical use in oncology, and ushered in a new era of rationally
      designed targeted agents in cancer therapeutics. It is currently approved for use
      in non-Hodgkin lymphoma (NHL), chronic lymphoid leukemia (CLL), and rheumatoid
      arthritis (RA). Rituximab is non-mutagenic, associated with low treatment-related
      toxicity, and few, if any, long term adverse events, making it an attractive
      agent to be tried in off-label settings like Hodgkin lymphoma (HL). HL consists
      of two distinct subtypes - classic HL (cHL) and lymphocyte predominant HL (LPHL).
      CD20 is present in virtually all patients with LPHL, and in a significant
      minority of patients with cHL. In this CD20 positive sub-population, the use of
      rituximab is a rational intervention strategy. Rituximab has been used in
      patients with cHL as well as LPHL with good efficacy. In this article, we provide
      a clinically-oriented overview of the use of rituximab in the different sub-types
      of HL, and report updated results of our series of 8 LPHL patients treated with
      rituximab. A systematic review of the literature is also presented.

PMID- 21183283
TI  - Social influences on the motivation to quit smoking: main and moderating effects
      of social norms.
AB  - The present study extends the previous research on the social influences on
      quitting by investigating inconsistencies between different types of social norms
      and their main and moderating effects on quitting intentions. The theory of
      planned behaviour (TPB) served as the theoretical framework. Social influences
      were operationalised by subjective quitting norm (significant others'
      expectations that one should quit), descriptive quitting norm (significant
      others' quitting behaviour), and descriptive smoking norm (partner's smoking).
      Because gender differences had previously been reported, norm effects were also
      analysed with respect to gender. A total of 168 smokers who had a partner (47%
      men, mean age M=34, SD=16) completed measures of TPB variables (including
      subjective quitting norm), descriptive quitting norm, descriptive smoking norm,
      and smoking behaviour. Subjective and descriptive quitting norms were more
      inconsistent in women than in men. The descriptive quitting norm enhanced the TPB
      prediction of intention by 5%. A three-way interaction accounted for an
      additional 3% of the variance and revealed both that subjective and descriptive
      quitting norms interacted in their prediction and that gender moderated this
      effect: the subjective quitting norm correlated positively to quitting intention
      only in women with a strong descriptive quitting norm. All analyses were
      controlled for number of cigarettes per day. These findings confirmed that it is
      important to distinguish subjective and descriptive norms and that differences
      exist in how these norms motivate women and men to quit smoking. Consistent
      quitting norms such as quitting of significant others in combination with their
      expectations that one should quit appear to be less common but more important in
      women to form a corresponding intention.

PMID- 21183284
TI  - Plaque rupture is not the cause of takotsubo cardiomyopathy.

PMID- 21183285
TI  - A medical device for prefabrication of large bone grafts in modern medicine.
AB  - Translating advances in the laboratory into sound clinical practice presents a
      series of formidable conceptual and technical challenges. One of them is our
      inability to maintain large grafts of living cells upon transfer from in vitro
      conditions into the host in vivo. This is due mainly to diffusion limitations
      within the grafting material. We embrace the well-known hypothesis of the
      "Diamond Concept" in bone tissue regeneration, which includes four key factors.
      Based on the understanding of basic elements of tissue engineering constructs,
      prefabrication and conditioning techniques and the nano-vascularisation of the
      scaffold, we furthermore hypothesize that combinations of cells, solid
      multipolymeric scaffold as the "core element" working as the extracellular matrix
      (ECM), growth factors and nano-vascularisation setting may eventually generate a
      large "ready-to-use"in vitro/in vivo graft. We are confident and think that
      growth factors will help in the construction of a step-by-step organisation of
      the bone tissue engineering construct (BTEC). A medical device, named in vitro/in
      vivo Bone Bioreactor Tissue Engineering Construct (IV2B2TEC), is proposed to
      fulfil the hypothesis. Soon, we hope to test the above hypothesis on a non-union
      bone defect in an animal model. This novel strategy will likely open new options
      for reconstructing extended bone defects and facilitate clinical translation of
      bone tissue engineering. As compared with conventional reconstructive methods,
      the strategy has four key advantages and might prove to be a novel armamentarium
      for clinicians in regenerative medicine.

PMID- 21183286
TI  - Frontal UV-visible fluorescence polarization measurement for bovine meat ageing
      assessment.
AB  - Among the techniques based on light interactions with biological tissues,
      fluorescence polarization offers a selective means of characterizing the
      organization of biological tissues. This paper presents a methodology for
      investigating the fluorescence polarization of muscle tissues in to obtain
      structural information, and specifically the structural modifications caused by
      meat ageing. A theoretical model of fluorescence anisotropy based on geometrical
      distribution and properties of tryptophan, the major fluorophore in muscle
      tissues, is proposed. Experimental data are fitted with the model and fitting
      parameters (C(1), C(2) and tau) are tracked during meat ageing. Results presented
      demonstrate how the method is able to show muscle structure modification during
      ageing. They highlight changes in structural proteins along the main axis of
      myofibrils and changes in the tryptophan environment resulting from the
      physicochemical and enzymatic processes at work during ageing.

PMID- 21183287
TI  - Stereotactic body radiotherapy as monotherapy or post-external beam radiotherapy
      boost for prostate cancer: technique, early toxicity, and PSA response.
AB  - PURPOSE: High dose rate (HDR) brachytherapy has been established as an excellent
      monotherapy or after external-beam radiotherapy (EBRT) boost treatment for
      prostate cancer (PCa). Recently, dosimetric studies have demonstrated the
      potential for achieving similar dosimetry with stereotactic body radiotherapy
      (SBRT) compared with HDR brachytherapy. Here, we report our technique, PSA nadir,
      and acute and late toxicity with SBRT as monotherapy and post-EBRT boost for PCa
      using HDR brachytherapy fractionation. PATIENTS AND METHODS: To date, 38 patients
      have been treated with SBRT at the University of California-San Francisco with a
      minimum follow-up of 12 months. Twenty of 38 patients were treated with SBRT
      monotherapy (9.5 Gy * 4 fractions), and 18 were treated with SBRT boost (9.5 Gy *
      2 fractions) post-EBRT and androgen deprivation therapy. PSA nadir to date for 44
      HDR brachytherapy boost patients with disease characteristics similar to the SBRT
      boost cohort was also analyzed as a descriptive comparison. RESULTS: SBRT was
      well tolerated. With a median follow-up of 18.3 months (range, 12.6-43.5), 42%
      and 11% of patients had acute Grade 2 gastrourinary and gastrointestinal
      toxicity, respectively, with no Grade 3 or higher acute toxicity to date. Two
      patients experienced late Grade 3 GU toxicity. All patients are without evidence
      of biochemical or clinical progression to date, and favorably low PSA nadirs have
      been observed with a current median PSA nadir of 0.35 ng/mL (range, <0.01-2.1)
      for all patients (0.47 ng/mL, range, 0.2-2.1 for the monotherapy cohort; 0.10
      ng/mL, range, 0.01-0.5 for the boost cohort). With a median follow-up of 48.6
      months (range, 16.4-87.8), the comparable HDR brachytherapy boost cohort has
      achieved a median PSA nadir of 0.09 ng/mL (range, 0.0-3.3). CONCLUSIONS: Early
      results with SBRT monotherapy and post-EBRT boost for PCa demonstrate acceptable
      PSA response and minimal toxicity. PSA nadir with SBRT boost appears comparable
      to those achieved with HDR brachytherapy boost.

PMID- 21183288
TI  - International brachytherapy practice patterns: a survey of the Gynecologic Cancer
      Intergroup (GCIG).
AB  - PURPOSE: To determine current practice patterns with regard to gynecologic high
      dose-rate (HDR) brachytherapy among international members of the Gynecologic
      Cancer Intergroup (GCIG) in Japan/Korea (Asia), Australia/New Zealand (ANZ),
      Europe (E), and North America (NAm). METHODS AND MATERIALS: A 32-item survey was
      developed requesting information on brachytherapy practice patterns and standard
      management for Stage IB-IVA cervical cancer. The chair of each GCIG member
      cooperative group selected radiation oncology members to receive the survey.
      RESULTS: A total of 72 responses were analyzed; 61 respondents (85%) used HDR.
      The three most common HDR brachytherapy fractionation regimens for Stage IB-IIA
      patients were 6 Gy for five fractions (18%), 6 Gy for four fractions (15%), and 7
      Gy for three fractions (11%); for Stage IIB-IVA patients they were 6 Gy for five
      fractions (19%), 7 Gy for four fractions (8%), and 7 Gy for three fractions (8%).
      Overall, the mean combined external-beam and brachytherapy equivalent dose (EQD2)
      was 81.1 (standard deviation [SD] 10.16). The mean EQD2 recommended for Stage IB
      IIA patients was 78.9 Gy (SD 10.7) and for Stage IIB-IVA was 83.3 Gy (SD 11.2) (p
      = 0.02). By region, the mean combined EQD2 was as follows: Asia, 71.2 Gy (SD
      12.65); ANZ, 81.18 (SD 4.96); E, 83.24 (SD 10.75); and NAm, 81.66 (SD, 6.05; p =
      0.02 for Asia vs. other regions).The ratio of brachytherapy to total prescribed
      dose was significantly higher for Japan (p = 0.0002). CONCLUSION: Although
      fractionation patterns may vary, the overall mean doses administered for cervical
      cancer are similar in Australia/New Zealand, Europe, and North America, with
      practitioners in Japan administering a significantly lower external-beam dose but
      higher brachytherapy dose to the cervix. Given common goals, standardization
      should be possible in future clinical trials.

PMID- 21183289
TI  - A putatively functional haplotype in the gene encoding transforming growth factor
      beta-1 as a potential biomarker for radiosensitivity.
AB  - PURPOSE: To determine whether genetic variability in TGFB1 is related to
      circulating transforming growth factor-beta1 (TGF-beta1) plasma concentrations
      after radiotherapy and to radiosensitivity of lymphoid cells. PATIENTS AND
      METHODS: Transforming growth factor-beta1 plasma concentrations (n=79) were
      measured in patients 1 year after radiotherapy and chromosomal aberrations (n=71)
      ex vivo before therapy start. Furthermore, TGF-beta1 secretion and apoptosis were
      measured in isolated peripheral blood mononuclear cells of 55 healthy volunteers.
      These phenotypes were analyzed in relation to five germline polymorphisms in the
      5' region of the TGFB1 gene. Because of high linkage disequilibrium, these five
      polymorphisms reflect frequent genetic variation in this region. A presumed
      impact of TGF-beta1 on DNA damage or repair was measured as micronucleus
      formation in 30 lymphoblastoid cell lines. RESULTS: We identified a
      hypofunctional genetic haplotype termed H3 tagging the 5' region of the TGFB1
      gene encoding TGF-beta1. H3 was associated with lower TGF-beta1 plasma
      concentrations in patients (p=0.01) and reduced TGF-beta1 secretion in irradiated
      peripheral blood mononuclear cells (p=0.003). Furthermore, cells with H3 were
      less prone to induction of chromosomal aberrations (p=0.001) and apoptosis
      (p=0.003) by irradiation. The hypothesis that high TGF-beta1 could sensitize
      cells to DNA damage was further supported by increased micronuclei formation in
      30 lymphoblastoid cell lines when preincubated with TGF-beta1 before irradiation
      (p=0.04). CONCLUSIONS: On the basis of TGF-beta1 plasma levels and radiation
      sensitivity of lymphoid cells, this study revealed a putatively hypofunctional
      TGFB1 haplotype. The significance of this haplotype and the suggested link
      between TGF-beta1 function and DNA integrity should be further explored in other
      cell types, as well as other experimental and clinical conditions.

PMID- 21183290
TI  - Spinal cord tolerance in the age of spinal radiosurgery: lessons from preclinical
      studies.
AB  - Clinical implementation of spinal radiosurgery has increased rapidly in recent
      years, but little is known regarding human spinal cord tolerance to single
      fraction irradiation. In contrast, preclinical studies in single-fraction spinal
      cord tolerance have been ongoing since the 1970s. The influences of field length,
      dose rate, inhomogeneous dose distributions, and reirradiation have all been
      investigated. This review summarizes literature regarding single-fraction spinal
      cord tolerance in preclinical models with an emphasis on practical clinical
      significance. The outcomes of studies that incorporate uniform irradiation are
      surprisingly consistent among multiple small- and large-animal models. Extensive
      investigation of inhomogeneous dose distributions in the rat has demonstrated a
      significant dose-volume effect while preliminary results from one pig study are
      contradictory. Preclinical spinal cord dose-volume studies indicate that dose
      distribution is more critical than the volume irradiated suggesting that neither
      dose-volume histogram analysis nor absolute volume constraints are effective in
      predicting complications. Reirradiation data are sparse, but results from guinea
      pig, rat, and pig studies are consistent with the hypothesis that the spinal cord
      possesses a large capacity for repair. The mechanisms behind the phenomena
      observed in spinal cord studies are not readily explained and the ability of dose
      response models to predict outcomes is variable underscoring the need for further
      investigation. Animal studies provide insight into the phenomena and mechanisms
      of radiosensitivity but the true significance of animal studies can only be
      discovered through clinical trials.

PMID- 21183291
TI  - Hypofractionation results in reduced tumor cell kill compared to conventional
      fractionation for tumors with regions of hypoxia.
AB  - PURPOSE: Tumor hypoxia has been observed in many human cancers and is associated
      with treatment failure in radiation therapy. The purpose of this study is to
      quantify the effect of different radiation fractionation schemes on tumor cell
      killing, assuming a realistic distribution of tumor oxygenation. METHODS AND
      MATERIALS: A probability density function for the partial pressure of oxygen in a
      tumor cell population is quantified as a function of radial distance from the
      capillary wall. Corresponding hypoxia reduction factors for cell killing are
      determined. The surviving fraction of a tumor consisting of maximally resistant
      cells, cells at intermediate levels of hypoxia, and normoxic cells is calculated
      as a function of dose per fraction for an equivalent tumor biological effective
      dose under normoxic conditions. RESULTS: Increasing hypoxia as a function of
      distance from blood vessels results in a decrease in tumor cell killing for a
      typical radiotherapy fractionation scheme by a factor of 10(5) over a distance of
      130 MUm. For head-and-neck cancer and prostate cancer, the fraction of tumor
      clonogens killed over a full treatment course decreases by up to a factor of
      ~10(3) as the dose per fraction is increased from 2 to 24 Gy and from 2 to 18 Gy,
      respectively. CONCLUSIONS: Hypofractionation of a radiotherapy regimen can result
      in a significant decrease in tumor cell killing compared to standard
      fractionation as a result of tumor hypoxia. There is a potential for large errors
      when calculating alternate fractionations using formalisms that do not account
      for tumor hypoxia.

PMID- 21183292
TI  - Comparison of macroscopic pathology measurements with magnetic resonance imaging
      and assessment of microscopic pathology extension for colorectal liver
      metastases.
AB  - PURPOSE: To compare pathology macroscopic tumor dimensions with magnetic
      resonance imaging (MRI) measurements and to establish the microscopic tumor
      extension of colorectal liver metastases. METHODS AND MATERIALS: In a prospective
      pilot study we included patients with colorectal liver metastases planned for
      surgery and eligible for MRI. A liver MRI was performed within 48 hours before
      surgery. Directly after surgery, an MRI of the specimen was acquired to measure
      the degree of tumor shrinkage. The specimen was fixed in formalin for 48 hours,
      and another MRI was performed to assess the specimen/tumor shrinkage. All MRI
      sequences were imported into our radiotherapy treatment planning system, where
      the tumor and the specimen were delineated. For the macroscopic pathology
      analyses, photographs of the sliced specimens were used to delineate and
      reconstruct the tumor and the specimen volumes. Microscopic pathology analyses
      were conducted to assess the infiltration depth of tumor cell nests. RESULTS:
      Between February 2009 and January 2010 we included 13 patients for analysis with
      21 colorectal liver metastases. Specimen and tumor shrinkage after resection and
      fixation was negligible. The best tumor volume correlations between MRI and
      pathology were found for T1-weighted (w) echo gradient sequence (r(s) = 0.99,
      slope = 1.06), and the T2-w fast spin echo (FSE) single-shot sequence (r(s) =
      0.99, slope = 1.08), followed by the T2-w FSE fat saturation sequence (r(s) =
      0.99, slope = 1.23), and the T1-w gadolinium-enhanced sequence (r(s) = 0.98,
      slope = 1.24). We observed 39 tumor cell nests beyond the tumor border in 12
      metastases. Microscopic extension was found between 0.2 and 10 mm from the main
      tumor, with 90% of the cases within 6 mm. CONCLUSIONS: MRI tumor dimensions
      showed a good agreement with the macroscopic pathology suggesting that MRI can be
      used for accurate tumor delineation. However, microscopic extensions found beyond
      the tumor border indicate that caution is needed in selecting appropriate tumor
      margins.

PMID- 21183293
TI  - [Non-obstructive azoospermia: option of the testicular sperm extraction performed
      on the day of oocyte retrieval].
AB  - OBJECTIVE: Analyzing the results and validating the procedure of testicular sperm
      extraction (TESE) performed on the day of oocyte retrieval in non obstructive
      azoospermia (NOA) patients. PATIENTS AND METHODS: Sixty TESE were performed on
      the day of oocyte retrieval (dOR), in 52 NOA men. Patients were sorted into three
      groups according to the results of the surgical procedure: 1: sperm recovery with
      possible sperm freezing (n=20); 2: sperm recovery without freezing (n=27); 3:
      "negative" biopsy (n=13). ICSI outcomes in the two groups with sperm recovery
      were compared to those of ICSI performed with frozen-thawed sperm obtained from
      TESE performed (n=13). RESULTS: The rate of positive sperm retrieval was 78%.
      While the overall clinical pregnancy rate was 50%, no difference in the
      fertilization, implantation and clinical pregnancy rates was found in the two
      groups with positive sperm retrieval as compared to frozen-thawed sperm group.
      Twelve pregnancies were obtained in patients without further sperm
      cryopreservation. CONCLUSION: After TESE in NOA men, cryopreserved sperm produced
      comparable results with freshly obtained sperm. However, TESE performed on dOR
      can offer the opportunity, in patients with rare sperm that might not survive
      freeze-thaw, to have a possible fresh embryo transfer. Couples should be
      counselled regarding the possibility of oocyte retrieval without sperm for ICSI.

PMID- 21183294
TI  - Clonal complex Pseudomonas aeruginosa in horses.
AB  - Pseudomonas aeruginosa is associated with infectious endometritis in horses.
      Although infectious endometritis is often considered a venereal infection, there
      is relatively limited genotypic-based evidence to support this mode of
      transmission. The study sought to determine the relatedness between genital P.
      aeruginosa isolates collected from a limited geographical region using molecular
      strain typing. Enterobacterial repetitive intergenic consensus PCR typing was
      performed on 93 isolates collected between 2005 and 2009 from 2058 thoroughbred
      horses (including 18 stallions) at 66 studs. While P. aeruginosa was not detected
      in the stallions, 53/93 (57%) mares harbouring P. aeruginosa had clonally related
      strains, which included a single dominant genotype detected in 42 (45%) mares
      from 13 different studs. These novel findings suggest that most equine genital P.
      aeruginosa infections in this region may have been acquired from mechanisms other
      than direct horse to horse transmission. Instead, other potential acquisition
      pathways, as well as strain specific adaptation to the equine genital tract,
      should be investigated.

PMID- 21183295
TI  - First morphological characterization of 'Candidatus Mycoplasma turicensis' using
      electron microscopy.
AB  - At least three haemotropic mycoplasmas have been recognized in cats: Mycoplasma
      haemofelis (Mhf), 'Candidatus Mycoplasma haemominutum' (CMhm) and 'Candidatus M.
      turicensis' (CMt). The latter was originally identified in a Swiss pet cat with
      haemolytic anaemia and shown to be prevalent in domestic cats and wild felids
      worldwide using molecular methods. So far, there has been no confirmatory
      morphological evidence of the existence of CMt presumably due to low blood loads
      during infection while CMhm has only been characterized by light microscopy with
      discrepant results. This study aimed to provide for the first time electron
      microscopic characteristics of CMt and CMhm and to compare them to Mhf. Blood
      samples from cats experimentally infected with CMt, CMhm and Mhf were used to
      determine copy numbers in blood by real-time PCR and for transmission and
      scanning electron microscopy. High resolution scanning electron microscopy
      revealed CMt and CMhm to be discoid-shaped organisms of 0.3 MUm in diameter
      attached to red blood cells (RBCs). In transmission electron microscopy of CMt,
      an oval organism of about 0.25 MUm with several intracellular electron dense
      structures was identified close to the surface of a RBC. CMhm and CMt exhibited
      similar morphology to Mhf but had a smaller diameter. This is the first study to
      provide morphological evidence of CMt thereby confirming its status as a distinct
      haemoplasma species, and to present electron microscopic features of CMhm.

PMID- 21183296
TI  - Differential expression of porcine testis proteins during postnatal development.
AB  - The development of the testes includes changes in cell morphology and endocrine
      levels that are essential for the maturation of males. A large number of novel
      proteins are expressed throughout testis development and play important roles in
      spermatogenesis. Differences in protein expressions during the development of
      porcine testes have not been systematically studied. The purpose of this study
      was to investigate differential protein expression in porcine testes during
      postnatal development. Testes from four pigs each at 1wk, 3mo, and 1yr of age
      were used for a proteomic analysis. Expression levels of 264 protein spots were
      quantified using the Melanie 3 software. In total, 108 protein spots showed more
      than 2-fold differences (P<0.05) among developmental stages, and 90 of them were
      successfully identified by mass spectrometry. The proteins were sorted based on
      whether the expression levels increased with age (36.1%), decreased with age
      (38.0%), or fluctuated among different developmental stages (25.9%). In total, 69
      unique gene products were further classified according to their gene ontology
      annotations. A majority of the proteins are organelle proteins (41%) with the
      nucleus and mitochondria being the main organelles. About 45% of the proteins
      have a protein binding domain and are likely involved in protein-protein
      interactions. Finally, a large proportion of these differentially expressed
      proteins are involved in cellular (25%) and metabolic (22%) processes.
      Identifying these differentially expressed proteins should be valuable for
      exploring developmental biology and the pathology of male reproduction.

PMID- 21183297
TI  - Deaths in Rotorua's geothermal hot pools: hydrogen sulphide poisoning.
AB  - In late 2007 and early 2008 two gentlemen were found dead in, or near to,
      enclosed hot pools fed with Rotorua's geothermal waters. Amidst much publicity
      the Coroner has ruled that the deaths were related to hydrogen sulphide
      poisoning. Following post mortem examinations, blood and urine samples were
      frozen and sent to the Toxicology Unit of ESR. These were then stored frozen
      until analysis. Hydrogen sulphide (H(2)S) is a potentially deadly gas at elevated
      levels, but is rapidly eliminated from the body and is unstable post mortem.
      Thiosulphate is a marker for the exposure to H(2)S, and as it is stable post
      mortem the samples were analysed to determine the thiosulphate levels present.
      The urine thiosulphate levels detected were above those seen in the urine samples
      measured from the only previous study of people exposed to the Rotorua thermal
      area and the blood levels were similar to literature values from fatalities
      exposed in workplaces such as sewage treatment plants.

PMID- 21183298
TI  - Letter to the Editor regarding the published study "Deaths involving serotonergic
      drugs".

PMID- 21183299
TI  - An analytical evaluation of eight on-site oral fluid drug screening devices using
      laboratory confirmation results from oral fluid.
AB  - The performance of eight on-site oral fluid drug screening devices was studied in
      Belgium, Finland and the Netherlands as a part of the EU-project DRUID. The main
      objective of the study was to evaluate the reliability of the devices for testing
      drivers suspected of driving under the influence of drugs (DUID). The performance
      of the devices was assessed by their ability to detect substances using cut-offs
      which were set at sufficiently low levels to allow optimal detection of positive
      DUID cases. The devices were evaluated for the detection of amphetamine(s),
      cannabis, cocaine, opiates and benzodiazepines when the relevant test was
      incorporated. Methamphetamine, MDMA and PCP tests that were included in some
      devices were not evaluated since there were too few positive samples. The device
      results were compared with confirmation analysis results in oral fluid. The
      opiates tests appeared to perform relatively well with sensitivity results
      between 69 and 90%. Amphetamines and benzodiazepines tests had lower sensitivity,
      although the DrugWipe test evaluated was promising for amphetamine. In
      particular, it is evident that the cannabis and cocaine tests of the devices
      still lack sensitivity, although further testing of the cocaine tests is
      desirable due to the low prevalence and low concentrations encountered in this
      study.

PMID- 21183300
TI  - Suicide of a cyclist.
AB  - The rate of suicides in road traffic fatalities is estimated at 1-8% depending on
      the investigated study material. Especially single-car accidents, for which no
      technical reason or driving error is apparent, are considered suspicious. The
      elucidation of suicides in road traffic is difficult if there are no relevant
      clues such as the announcement of suicide plans shortly before the event or a
      suicide note. Individuals who intentionally kill themselves in road traffic often
      have a history of mental illness. The authors report on a suicide using a
      bicycle. A 71-year-old man intentionally drove into the wall of a house situated
      at the end of a hill road and suffered an open craniocerebral trauma and an
      aortic rupture. The pattern of findings and the circumstances of the case are
      described.

PMID- 21183302
TI  - Vascular patterns in nodules of intraductal papillary mucinous neoplasms depicted
      under contrast-enhanced ultrasonography are helpful for evaluating malignant
      potential.
AB  - OBJECTIVES: The purpose of this study is to evaluate the feasibility of contrast
      enhanced ultrasonography (CE-US) to differentiate between benign and malignant
      intraductal papillary mucinous neoplasms (IPMN). PATIENTS AND METHODS: Contrast
      enhanced ultrasonography with a contrast agent was performed on 22 consecutive
      patients with IPMN suspected of being malignant. This revealed 10 carcinomas, 1
      borderline lesion and 11 adenomas. All patients underwent surgery, and the
      histological diagnosis was confirmed by examination of resected specimens. CE-US
      was performed using a contrast agent. The detection rates of mural nodules were
      compared between CE-US and contrast-enhanced computed tomography (CE-CT), and the
      imaging of mural nodules depicted under CE-US was analyzed. RESULTS: Seventeen of
      22 resected specimens (77.3%) had mural nodules. There was no significant
      difference in the detection rate between CE-US (n=15; 88.2%) and CE-CT (n=12;
      70.6%). In 12 (80.0%) of these patients, CE-US revealed small vessels in the
      mural nodule. The spotty or linear-shaped pattern was detected in 4 patients and
      the branch-shaped pattern in 8. The branch-shaped pattern lesion was associated
      with carcinoma. These mural nodules were 10mm or more in height. In the perfusion
      image phase, cystic walls and mural nodules were also enhanced in all cases.
      CONCLUSION: The vessel shapes of the mural nodules depicted under CE-US were
      associated with size and pathological findings. These results suggested that CE
      US with a contrast agent is a powerful modality with which to evaluate the
      malignant potential of IPMN.

PMID- 21183303
TI  - HRCT findings in the lungs of non-smokers with neurofibromatosis.
AB  - PURPOSE: Interstitial lung disease in neurofibromatosis (NF) has been disputed
      and attributed to smoking-related changes. The aim of this study was to describe
      HRCT findings in the lungs of non-smokers with NF. MATERIALS AND METHODS: Six
      never-smokers with NF underwent lung HRCT. Two radiologists evaluated the HRCT
      scans and a final decision was reached by consensus. The HRCT scans were analyzed
      with regard to the number, size, location (upper, middle or lower lung zone) and
      distribution (peripheral and central) of lung cysts and the presence of ground
      glass density centrilobular micronodules. RESULTS: All patients with NF had small
      (2-18 mm) thin wall cysts and upper-lobe predominant patchy areas of ground-glass
      density centrilobular micronodules. In five cases, there were 3-17 cysts and in
      one there were numerous (>100). Lung cysts were central (1), subpleural (1) and
      in both locations (4). CONCLUSION: Interstitial lung disease in NF is not
      associated with smoking and may be entirely asymptomatic. HRCT may reveal small
      cysts, with barely perceptible walls therefore not representing emphysema and
      occasionally a minimal micronodular pattern of ground glass opacity. There was no
      radiologic evidence of lung fibrosis, honeycombing or severe bullous disease.

PMID- 21183304
TI  - Capillary electrophoresis of phytochemical substances in herbal drugs and
      medicinal plants.
AB  - This paper reviews the applications of electromigration methods in analysis of
      phytochemical substances in herbal drugs and medicinal plants. A short
      description of the basic principles of capillary electrophoretic techniques is
      firstly given, then the overview deals with the applications of selected methods
      published in the period 2005-2010. The phytochemical substances have been
      classified according to their chemical nature (e.g. alkaloids, polyphenols,
      carbohydrates, lipids, terpenes) and the applied CE approaches, namely CZE, NACE,
      MEKC, MEEKC and CEC, together with the different detection methods, are
      critically discussed for each of the considered classes of natural compounds.

PMID- 21183305
TI  - Identifying teachable moments for health behavior counseling in primary care.
AB  - OBJECTIVE: Situations with potential to motivate positive change in unhealthy
      behavior have been called 'teachable moments'. Little is known about how they
      occur in the primary care setting. METHODS: Cross-sectional observational design.
      Audio-recordings collected during 811 physician-patient interactions for 28
      physicians and their adult patients were analyzed using conversation analysis.
      RESULTS: Teachable moments were observed in 9.8% of the cases, and share three
      features: (1) the presence of a concern that is salient to the patient that is
      either obviously relevant to an unhealthy behavior, or through conversation comes
      to be seen as relevant; (2) a link that is made between the patient's salient
      concern and a health behavior that attempts to motivate the patient toward
      change; and (3) a patient response indicating a willingness to discuss and commit
      to behavior change. Additionally, we describe phenomena related to, but not
      teachable moments, including teachable moment attempts, missed opportunities, and
      health behavior advice. CONCLUSIONS: Success of the teachable moment rests on the
      physician's ability to identify and explore the salience of patient concerns and
      recognize opportunities to link them with unhealthy behaviors. PRACTICE
      IMPLICATIONS: The skills necessary for accomplishing teachable moments are well
      within the grasp of primary care physicians.

PMID- 21183306
TI  - SARL: shoulder acronyms. A review of the literature.
AB  - Acronyms are words formed by taking the first initial or other parts of words
      from a compound term. They are designed to help communicate ideas efficiently. In
      the literature pertaining to shoulder surgery, a variety of acronyms have been
      offered for normal anatomic states, physical examination findings, pathologic
      conditions, surgical techniques, and outcome instruments, with new acronyms
      offered each year. The purpose of this article is to review and clearly define
      acronyms used by shoulder specialists.

PMID- 21183307
TI  - [Non-invasive haemodynamic assessment in paediatric intensive care unit: reply].

PMID- 21183308
TI  - [Acute visceral ischaemia, early complication of the aortic syndrome: how to
      detect and manage it?].
AB  - Visceral malperfusion as a complication of aortic dissection represent 20 % of
      all type A or B aortic dissections. Visceral ischaemia is a factor of poor
      prognosis resulting in a higher mortality for these patients, yet, its clinical
      diagnosis is often underestimated. In all cases, the cross-sectional imaging,
      especially computed tomography, is needed to precise the mechanism of ischaemia.
      It allows differentiating dynamic from static ischaemia and thus to adapt its
      management. Endovascular treatment of ischaemia has been developed because it
      allows to a rapid treatment with a high success and low complication rates. Early
      results of aortic stentgrafting and aortic fenestration are up to 96 %, but late
      changes on the morphology or function reperfused gut was not studied.

PMID- 21183309
TI  - [Acute aortic syndrome: medical care at acute phase and long-term follow-up].
AB  - For the management of acute aortic syndromes, there is a major interest of a
      multidisciplinary decision: resuscitator, cardiologist, radiologist, vascular
      surgeons. Do not delay the thoracic computed tomography: the gold standard in
      such an urgent situation. Use intravenous beta-blocade therapy anytime it is
      possible. At the acute phase: systolic blood pressure target is < 120 mmHg, and
      the heart rhythm target is < 60 bpm. Type A acute aortic dissection is a surgical
      emergency. Type B acute aortic dissection is a medical emergency and need a
      management of peripheral ischemia and/or organ failures if necessary. Beta
      blocade therapy has to be pursued indefinitely at discharge. The angiotensin II
      receptor blockers (ARB) could be a future treatment in patient swith a Marfan
      syndrome. All etiological investigations of hypertension are systematically
      performed. Cardiovascular risk stratification and management is mandatory.
      Educational support and use of ambulatory blood pressure monitoring. Clinical and
      MRI follow-up at six month and then once a year, and in any case of suspicious
      clinical manifestations are needed.

PMID- 21183310
TI  - Childhood trauma and current psychological functioning in adults with social
      anxiety disorder.
AB  - Etiological models of social anxiety disorder (SAD) suggest that early childhood
      trauma contributes to the development of this disorder. However, surprisingly
      little is known about the link between different forms of childhood trauma and
      adult clinical symptoms in SAD. This study (1) compared levels of childhood
      trauma in adults with generalized SAD versus healthy controls (HCs), and (2)
      examined the relationship between specific types of childhood trauma and adult
      clinical symptoms in SAD. Participants were 102 individuals with generalized SAD
      and 30 HCs who completed measures of childhood trauma, social anxiety, trait
      anxiety, depression, and self-esteem. Compared to HCs, individuals with SAD
      reported greater childhood emotional abuse and emotional neglect. Within the SAD
      group, childhood emotional abuse and neglect, but not sexual abuse, physical
      abuse, or physical neglect, were associated with the severity of social anxiety,
      trait anxiety, depression, and self-esteem.

PMID- 21183311
TI  - Parkes-Weber syndrome and giant superficial femoral artery aneurysm. Treatment by
      endovascular therapy and follow-up of 8 years.
AB  - Congenital vascular malformations represent a wide number of diseases with a
      great variability of clinical features. The association between congenital
      vascular malformations and peripheral aneurysms is very rare. The present study
      reports a case of giant superficial femoral artery aneurysm (7-cm-long)
      associated with Parkes-Weber syndrome (capillary malformation, multiple
      arteriovenous fistulas [AVFs], skeletal hypertrophy of the affected limb) treated
      by positioning two covered self-expandable endoprostheses after embolization of
      AVFs with Gianturco coils. The peri- and postoperative course was uneventful and
      the postprocedural angiography showed the complete exclusion of the aneurysm sac.
      At last follow-up, after 87 months, the duplex scan and computed tomography scan
      showed regular patency of the vessels with thrombosis of the aneurysm sac and the
      presence of a large number of AVFs. The association between Parkes-Weber syndrome
      and peripheral aneurysms represents a very unusual entity. The lack of evidence
      does not allow the establishment of the most suitable treatment for this disease.
      Endovascular approach associated with previous embolization of AVFs may represent
      a valid alternative to traditional surgical repair, which is still burdened by a
      high percentage of complications and failures.

PMID- 21183312
TI  - Use of 3.0-Tesla high spatial resolution magnetic resonance imaging for diagnosis
      and treatment of cystic adventitial disease of the popliteal artery.
AB  - Cystic adventitial disease (CAD) of the popliteal artery is a rare vascular
      disease of unknown etiology in which a mucin-containing cyst develops in the
      adventitial layer of the artery. Early recognition and treatment of this
      condition will prevent progression of the popliteal thrombosis and critical
      ischemia. However, diagnosis of the condition is difficult. The combination of
      contrast-enhanced magnetic resonance (MR) angiography and the excellent soft
      tissue resolution of MR imaging allow for detailed evaluation of patients with
      CAD and facilitate appropriate management decisions. We report the 3.0-Tesla MR
      imaging features of CAD in three patients and discuss the interest for this
      noninvasive imaging technique in such a setting.

PMID- 21183313
TI  - Unstable patients with retroperitoneal vascular trauma: an endovascular approach.
AB  - BACKGROUND: In hemodynamically unstable patients, the management of
      retroperitoneal vascular trauma is both difficult and challenging. Endovascular
      techniques have become an alternative to surgery in several trauma centers.
      METHODS: Between 2004 and 2006, 16 patients (nine men, mean age: 46 years, range:
      19-79 years) with retroperitoneal vascular trauma and hemodynamic instability
      were treated using an endovascular approach. The mean injury severity score was
      30.7 +/- 13.1. Mean systolic blood pressure and the shock index were 74 mm Hg and
      1.9, respectively. Vasopressor drugs were required in 68.7% of cases (n = 11).
      Injuries were attributable to road traffic accidents (n = 15) and falls (n = 1).
      The hemorrhage sites included the internal iliac artery or its branches (n = 12)
      with bilateral injury in one case, renal artery (n = 2), abdominal aorta (n = 1),
      and lumbar artery (n = 1). RESULTS: In all, 14 coil embolizations and three stent
      grafts were implanted. The technical success rate was 75%, as early re
      embolization was necessary in one case and three patients died during the
      perioperative period. Six patients died during the period of hospitalization
      (37.5%). No surgical conversion or major morbidity was reported. CONCLUSION: In
      comparison with particulates, coil +/- stent-graft may provide similar efficacy
      with regard to survival, and thus may be a valuable solution when particulate
      embolization is not available or feasible.

PMID- 21183314
TI  - Treatment of a ballistic wound of the common carotid artery revealed by a
      spontaneous carotid-jugular fistula.
AB  - The case reported is of a 30-year-old patient with a left internal carotid
      jugular fistula secondary to the explosion of an improvised explosive device
      during the Afghan war. Carotid resection with arterial bypass using a venous
      allograft and internal jugular ligation were performed by left cervicotomy
      associated with sternotomy at a specialized center. The management of cervical
      arteriovenous fistulas that occur as a result of penetrating trauma faced during
      the war must be considered and it should be noted that, on battlefields,
      treatment is not always performed in specialized units.

PMID- 21183315
TI  - Juvenile temporal vasculitis: a rare case in a middle-aged woman.
AB  - BACKGROUND: Classic giant cell arteritis affects older adults who are aged >50
      years. Temporal arteritis is uncommon in young adults but juvenile temporal
      vasculitis (JTV) is the most frequent form found in young people. Clinical
      presentation is usually poor, with localized temporal inflammatory changes
      without consistent systemic manifestations. Generally, the patients have a benign
      clinical course, without ophthalmic or ischemic manifestations. In these rare
      JTVs, excision of the involved section of temporal artery is often curative and
      corticosteroid therapy is not required. METHOD: The present study reports a case
      of JTV in a middle-aged woman. RESULTS: A 44-year-old woman complained of violent
      temporal headache, with a slight inflammatory syndrome. She had no vascular
      systemic manifestation and no cause of secondary vasculitis. Doppler
      ultrasonography suggested a localized inflammatory arteritis. Temporal biopsy was
      performed. Histologic findings were compatible with JTV (nongranulomatous
      panarteritis with mononuclear cells and eosinophils). All the symptoms
      disappeared after excision. One year later, she remains well and reports neither
      systemic manifestation nor recurrence. CONCLUSION: Vasculitis of the temporal
      arteries in young people is uncommon and JTV is rare in middle-aged people. It is
      necessary to search for systemic or secondary vasculitis. In contrast to giant
      cell arteritis, steroids are not required.

PMID- 21183316
TI  - Specially processed cereals diet increases plasma levels of active antisecretory
      factor and up-regulates rat hepatic glutathione S-transferase mu.
AB  - OBJECTIVE: Antisecretory factor (AF) inhibits pathologic fluid secretion and
      inflammation. AF is expressed in most tissues and is secreted into the blood.
      Challenge with bacterial enterotoxins increases AF activity. The plasma level of
      active AF is also increased after intake of certain food constituents, such as
      specially processed cereals, SPC. The exact molecular events that mediate these
      responses have remained obscure. The objective of this study was to investigate
      changes in protein expression in liver after SPC diet. METHODS: Rats were fed SPC
      or standard rodent diet for 18 d. The induction of AF in plasma was tested by
      ELISA. Changes in the liver proteome were analyzed by using 2D DIGE and LC-MS/MS.
      Further characterizations were done with Western blot and immunohistochemistry
      studies. RESULTS: The AF activity was increased after intake of SPC. Equivalent
      to recombinant AF, 6.6 +/- 1.09 ng/well could be detected in control plasma
      compared to 26 +/- 5.73 ng/well in plasma after SPC treatment. We found that the
      protein level of glutathione S-transferase mu (GST mu) was significantly up
      regulated 1.2-fold in rat liver after stimulation with SPC (wheat). The result
      was further confirmed by Western blot analysis. Immunohistochemistry showed
      staining for GST mu1 and AF preferentially in the central parts of the liver
      lobuli. CONCLUSION: Given the known role of GST mu1 in inducing defense, our
      results suggest that SPC-induced GST mu1 up-regulation can contribute to the
      positive clinical effects seen by SPC treatment.

PMID- 21183317
TI  - Lipopolysaccharide enhances glutaric acid-induced seizure susceptibility in rat
      pups: behavioral and electroencephalographic approach.
AB  - Glutaric acidemia type I (GA-I) is an inherited metabolic disease characterized
      by accumulation of glutaric acid (GA) and seizures. Considering that seizures are
      precipitated by common infections in children with GA-I, we investigated whether
      lipopolysaccharide (LPS) modifies GA-induced electrographic and neurochemical
      alterations in 21 days-old rats. The effect of LPS on convulsive behavior and
      electroencephalographic (EEG) alterations induced by GA (0.13; 0.4; 1.3
      MUmol/striatum) was determined in freely moving rats. After EEG recordings, we
      measured the levels of interleukin 1beta (IL-1beta) in GA-injected striatum. The
      injection of LPS (2mg/kg; i.p.) 6h before of GA administration, reduced the
      latency and increased the duration of seizures induced by GA (1.3 MUmol/site). In
      addition, LPS administration increased IL-1beta striatal levels, which positively
      correlated with total time in seizures. The intrastriatal injection of an IL
      1beta antibody (200 ng/2 MUl) prevented the facilitation of GA-induced seizures
      by LPS. These data suggest that inflammatory processes during critical periods of
      development may decrease GA-induced seizure threshold.

PMID- 21183318
TI  - Early risk factors for suicide in an epidemiological first episode psychosis
      cohort.
AB  - BACKGROUND: Much remains unknown about whether there are early risk factors for
      suicide in psychosis. AIM: The aim of the study was to determine whether there
      are any identifiable early symptom clusters, aetiological factors or illness
      course markers for suicide in first episode psychosis. METHOD: A total of 2132
      patients with first episode psychosis presenting to secondary care services in
      London (1965-2004; n=1474), Nottingham (1997-1999; n=195) and Dumfries and
      Galloway (1979-1998; n=463) were traced after up to 40 years (mean 13 years)
      following first presentation. Risk factors were identified from the Operational
      Checklist for Psychotic Disorders rated for the first year following
      presentation. RESULTS: Overall, there were 51 suicides and 373 deaths from other
      causes. Male gender (RR 2.84, 95% CI 1.20-6.69, p=0.02) and a cumulative
      threshold effect of symptoms early in the illness (RR 6.81, 95% CI 2.33-19.85,
      p<0.001) were associated with a higher propensity for later completed suicide.
      There was also a suggestion that early manic symptoms might increase the risk of
      later suicide irrespective of initial diagnosis. CONCLUSION: Suicide risk was
      associated with a cumulative threshold effect of symptoms and manic symptoms. As
      suicide is a relatively rare event in psychotic disorders, general population
      based prevention strategies may have more impact in this vulnerable group as well
      as the wider population.

PMID- 21183319
TI  - Regulation of pathological lymphangiogenesis requires factors distinct from those
      governing physiological lymphangiogenesis.
AB  - Physiological lymphangiogenesis requires key factors such as vascular endothelial
      growth factor (VEGF)-C and the homeodomain transcription factor Prox1 to induce
      the formation of primitive lymph sacs from veins during mammalian development.
      However, pathological lymphangiogenesis, defined as new lymphatic vessel growth
      resulting from pathogenic stimuli, may utilize additional signaling pathways
      and/or cell types in conditions such as tumor progression or inflammatory
      responses. In fact, although both physiological and pathological lymphatic
      vascular development share fundamental mechanisms, pleiotropic growth factors
      and/or pro-inflammatory cytokines mediate lymphangiogenesis in experimental
      models of pathologic lymphangiogenesis. This review summarizes molecular
      mechanisms underlying lymphangiogenesis in pathological conditions and focuses in
      particular on current findings relevant to tumor-associated lymphangiogenesis.

PMID- 21183320
TI  - Congenital cutis laxa syndrome maps to a novel locus on chromosome 9q13-q21.32.

PMID- 21183321
TI  - Quantification of activated and total caspase-14 with newly developed ELISA
      systems in normal and atopic skin.
AB  - BACKGROUND: Activation of caspase-14 occurs during terminal differentiation of
      keratinocytes and may play a role in filaggrin degradation. Therefore, down
      regulation of caspase-14 may lead to impaired barrier function. OBJECTIVE: To
      compare the levels of active and total caspase-14 in healthy subjects in various
      age groups and in patients with atopic dermatitis (AD), using two enzyme-linked
      immunoassay (ELISA) systems. METHODS: We established four clones of monoclonal
      antibodies to caspase-14 and used clone 3 as the immobilizing antibody. A
      cleavage site-directed antibody, h14D146 [4] was used for specific quantification
      of active caspase-14 in extracts of tape-stripped corneocytes. Total caspase-14
      was measured with a commercial antibody, H-99. RESULTS: The amount of caspase-14
      remained constant (ca. 0.1% of extractable proteins) in healthy males from their
      twenties to their fifties. Caspase-14 was mostly in active form (71-94%) in these
      extracts. In contrast, caspase-14 level and active caspase-14 ratio were
      significantly decreased in females in their fifties and sixties. Contents of free
      amino acids were decreased in females in their sixties, and transepidermal water
      loss was increased in females in their forties and sixties. In patients with AD,
      active caspase-14 was markedly down-regulated compared to age-matched controls in
      both lesional (7.5%) and non-lesional skin (10.6%). Staining of active caspase-14
      was considerably weaker in non-lesional skin and was hardly detectable in
      lesional skin with parakeratosis. CONCLUSION: Our new ELISA systems are effective
      tools to quantify activation of caspase-14. Our results indicate a role of
      caspase-14 in epidermal barrier function.

PMID- 21183322
TI  - Modulatory effects of vitamin E, acetyl-L-carnitine and alpha-lipoic acid on new
      potential biomarkers for Alzheimer's disease in rat model.
AB  - Alzheimer's disease (AD) is the most common chronic neurodegenerative disorder
      associated with aging. This study aimed to explore new markers for AD as total
      homocysteine (tHcy), insulin, insulin like growth factor-1 (IGF-1), interlukin
      1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha); to determine the
      modulatory effects of vitamin E (VE), acetyl-L-carnitine (ALC) and alpha-lipoic
      acid (LA) on the investigated parameters and to evaluate the possible therapeutic
      role of these nutraceutical in AD-induced in rats. Our results revealed that
      brain acetylcholine esterase (AChE) activity and tHcy levels were significantly
      increased in AD model. Folic acid, vitamin B(12) levels and Na(+)/K(+) ATPase
      activity were markedly reduced. Plasma insulin and IGF-1 levels were noticeably
      decreased but plasma TNF-alpha and IL-1beta concentrations were significantly
      increased, confirming that abnormal inflammatory response is associated with AD.
      Treatment by VE, ALC and LA restored the above mentioned parameters to about
      normal levels comparable to those of donepezil, indicating that tHcy, insulin,
      IGF-1, IL-1beta and TNF-alpha may be considered as new biomarkers for AD. The
      study points to the potential restoring effects of VE, ALC and LA in AD model.
      Our study provides evidence for the importance of dietary supplementation in
      delaying the progression of age-related neurodegenerative diseases.

PMID- 21183323
TI  - In vitro protective effects of colon-available extract of Camellia sinensis (tea)
      against hydrogen peroxide and beta-amyloid (Abeta((1-42))) induced cytotoxicity
      in differentiated PC12 cells.
AB  - There is mounting evidence that the deposition and aggregation of beta-amyloid
      peptides (Abeta) in the brain play a significant role in the development and
      pathogenesis of Alzheimer's disease. There is further evidence that free radical
      species such as hydrogen peroxide (H(2)O(2)) mediate Abeta induced toxicity.
      Previous studies have demonstrated that green tea polyphenols possess
      neuroprotective properties through their ability to ameliorate oxidative stress
      induced by free radical species. Green tea polyphenols have also been shown to
      enhance cognition in various animal models of induced cognitive impairment. Upon
      ingestion, green tea polyphenols are metabolised and undergo bio-transformation
      which affects their bioavailability and therefore efficacy. In this study, a
      green tea extract was subjected to a simulated gastrointestinal digestion and a
      'colon-available' extract (CAGTE) prepared and assessed for its potential
      protective effects against H(2)O(2) and Abeta((1-42)) induced cytotoxicity using
      differentiated PC12 cells (dPC12) as a model for neuronal cells. CAGTE represents
      green tea phytochemicals potentially available after upper gastrointestinal
      digestion. CAGTE which was depleted in flavan-3-ols, as shown by LC-MS analysis,
      protected dPC12 cells at concentration ranges of 0.3-10 MUg/ml and 0.03-0.125
      MUg/ml for H(2)O(2) and Abeta((1-42)), induced cytotoxicity, respectively. At
      high concentrations, CAGTE exhibited direct anti-proliferative effects, in line
      with the reputed anti-cancer properties of green tea polyphenols. These results
      demonstrate that potentially bioavailable green tea metabolites are able to
      ameliorate both H(2)O(2) and Abeta((1-42)) induced cytotoxicity.

PMID- 21183324
TI  - The neuroprotective effect of olive leaf extract is related to improved blood
      brain barrier permeability and brain edema in rat with experimental focal
      cerebral ischemia.
AB  - Recent studies suggest that olive extracts suppress inflammation and reduce
      stress oxidative injury. We sought to extend these observations in an in vivo
      study of rat cerebral ischemia-reperfusion injury. Four groups, each of 18 Wister
      rats, were studied. One (control) group received distilled water, while three
      treatment groups received oral olive leaf extract (50, 75 and 100mg/kg/day
      respectively). After 30 days, blood lipid profiles were determined, before a 60
      min period of middle cerebral artery occlusion (MCAO). After 24h reperfusion,
      neurological deficit scores, infarct volume, brain edema, and blood-brain barrier
      permeability were each assessed in subgroups of six animals drawn from each main
      group. Olive leaf extract reduced the LDL/HDL ratio in doses 50, 75, and
      100mg/kg/day in comparison to the control group (P<0.001), and offered
      cerebroprotection from ischemia-reperfusion. For controls vs. doses of
      50mg/kg/day vs. 75 mg/kg/day vs. 100mg/kg/day, attenuated corrected infarct
      volumes were 209.79 +/- 33.05 mm(3) vs. 164.36 +/- 13.44 mm(3) vs. 123.06 +/-
      28.83 mm(3) vs. 94.71 +/- 33.03 mm(3); brain water content of the infarcted
      hemisphere 82.33 +/- 0.33% vs. 81.33 +/- 0.66% vs. 80.75 +/- 0.6% vs. 80.16 +/-
      0.47%, and blood-brain barrier permeability of the infarcted hemisphere 11.22 +/-
      2.19 MUg/g vs. 9.56 +/- 1.74 MUg/g vs. 6.99 +/- 1.48 MUg/g vs. 5.94 +/- 1.73
      MUg/g tissue (P<0.05 and P<0.01 for measures in doses 75 and 100mg/kg/day vs.
      controls respectively). Oral administration of olive leaf extract reduces infarct
      volume, brain edema, blood-brain barrier permeability, and improves neurologic
      deficit scores after transient middle cerebral artery occlusion in rats.

PMID- 21183325
TI  - Commonly used leukotriene B4 receptor antagonists possess intrinsic activity as
      agonists in human endothelial cells: Effects on calcium transients, adhesive
      events and mediator release.
AB  - Leukotriene B4 (LTB4), a potent chemotactic and immune-modulating lipid mediator,
      signals via two receptors, BLT1 and BLT2, leading to pro-inflammatory responses
      in phagocytes. Recently, we reported that BLT1 is the predominating BLT on human
      umbilical vein endothelial cells (HUVEC) and transmits a variety of functional
      responses. Here, we demonstrate that, in HUVEC, two BLT1 antagonists (U75302,
      CP105696) and one BLT2 antagonist (LY255283) possess intrinsic but varying
      agonist activity for adhesion of neutrophils, up-regulation of E-selectin, ICAM-1
      and VCAM-1, and release of MCP-1. These effects were observed after exposure of
      HUVEC for the drugs for 0.25-6h, persisted for several hours, and were less
      potent in magnitude as those elicited by LPS. Our findings may have consequences
      for interpretation of in vitro BLT blockade experiments.

PMID- 21183326
TI  - Aclidinium bromide improves exercise endurance and lung hyperinflation in
      patients with moderate to severe COPD.
AB  - BACKGROUND: Static and dynamic lung hyperinflation are associated with exercise
      impairment and poor outcomes in COPD patients. Aclidinium bromide is a novel,
      long-acting inhaled muscarinic antagonist currently in development for COPD
      treatment. METHODS: Patients with moderate to severe COPD (N = 181) were
      randomized to once-daily aclidinium 200 MUg or placebo for 6 weeks. Constant work
      rate cycling exercises at 75% of peak work rate were performed at baseline, Day
      1, Week 3, and Week 6. The primary efficacy measure was change in exercise
      endurance time (ET) from baseline to Week 6. Secondary outcomes included changes
      in trough forced expiratory volume in 1 s (FEV(1)), inspiratory capacity (IC),
      IC/total lung capacity (TLC), and functional residual capacity (FRC) from
      baseline to Day 1, Week 3, and Week 6. Borg dyspnea scores during exercise, locus
      of symptom limitation, and safety measures were assessed. RESULTS: Aclidinium
      significantly improved ET on Day 1 (P = 0.0002), and improvements were sustained
      through Week 3 (P = 0.0007) and Week 6 (P = 0.0042) vs placebo. Compared with
      placebo, aclidinium improved trough FEV(1), IC, and IC/TLC at Weeks 3 and 6 (P <
      0.05 for all). Exertional dyspnea scores at isotime were reduced on Day 1, Week
      3, and Week 6 for aclidinium vs placebo (P < 0.05). Furthermore, the likelihood
      of stopping exercise due to breathing discomfort was lower in the aclidinium
      group at study end (P = 0.0208) compared with placebo. No differences in safety
      outcomes were reported between treatments. CONCLUSIONS: Aclidinium significantly
      increased exercise tolerance, improved airflow obstruction and lung
      hyperinflation, and was safe and well tolerated. REGISTRATION OF TRIAL: This
      trial was registered with ClinicalTrials.gov (NCT00500318) under the name "A
      Study of Exercise Endurance and Lung Hyperinflation in Patients with Moderate to
      Severe COPD".

PMID- 21183327
TI  - Severe obstructive sleep apnea increases cystatin C in clinically latent renal
      dysfunction.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) increases the risk of cardiovascular
      disease (CVD) and has been reported to be associated with chronic kidney disease
      (CKD). Recent studies have demonstrated that cystatin C is a prognostic biomarker
      of the risk of death and CVD even in patients without established CKD. METHODS:
      In a cross-sectional study, we enrolled 267 consecutive OSA patients without CKD
      who had an apnea-hypopnea index (AHI) >= 5 events per hour in overnight
      polysomnography. CKD was defined as an estimated glomerular filtration rate
      (eGFR) < 60 mL/min/1.73 m(2) according to the modification of diet in renal
      disease (MDRD) equation (modified for Japanese). Serum cystatin C levels were
      measured in all patients. RESULTS: Cystatin C was significantly correlated with
      age (r = 0.37), body mass index (BMI) (r = 0.12), AHI (r = 0.17), C-reactive
      protein (CRP) (r = 0.12), and Brachial-ankle pulse wave velocity (r = 0.18).
      Logistic regression analysis demonstrated that severe OSA defined by an AHI >= 30
      events per hour was an independent variable for the highest quartiles of serum
      cystatin C levels (>=0.88 mg/L) (OR: 2.04, 95% CI: 1.04-4.01, P = 0.04) even
      after adjustment for age, BMI >= 25, hypertension, and diabetes mellitus.
      CONCLUSIONS: This study indicates that severe OSA independently increases serum
      cystatin C levels in patients without CKD. Cystatin C is considered to be a
      biomarker that reflects both clinically latent renal dysfunction and
      cardiovascular risk that are influenced by OSA.

PMID- 21183328
TI  - Serum gamma-glutamyl transferase activity is an independent predictor for
      cardiovascular disease in obstructive sleep apnea syndrome.
AB  - Gamma glutamyl transferase (GGT) is a new marker for predicting myocardial
      infarction, stroke, cardiac death and inflammation. There is also a strong
      relationship between Obstructive Sleep Apnea Syndrome (OSAS) and cardiovascular
      disease. This study was designed to investigate the association between serum GGT
      levels and cardiovascular disease in patients with OSAS, and relationship between
      severity of OSAS and serum GGT level. We evaluated the medical records of 166
      subjects who were admitted for sleep study. OSAS was diagnosed by polysomnography
      if Apnea-Hypopnea Index (AHI) > 5. According to AHI, individuals in whom AHI< 5
      were recruited as group 1 (OSAS negative group), AHI = 5-15: group 2 (mild OSAS
      group), AHI = 15-30: group 3 (moderate OSAS group), AHI >30: group 4 (severe OSAS
      group). Cardiovascular disease was defined if the patients had heart failure,
      coronary artery disease or arrhythmia. Of the subjects, 112 (67.5%) were male and
      the mean age was 54.3 +/- 12.2 years. There were 22 patients (13.2%), 17 patients
      (10.2%), 34 patients (20.4%) and 93 patients (56.2%) in group 1, 2, 3 and 4,
      respectively. There is a significant increase in serum GGT levels while AHI score
      increases (group 1 = 28.0 +/- 10.1, group 2 = 33.8 +/- 13.2, group 3 = 35.2 +/-
      8.5, group 4 = 40.0 +/- 22.0; p for trend = 0.024). However, serum C-reactive
      protein (CRP), alanine aminotransferase and aspartate aminotransferase levels
      were similar in all groups (p > 0.05). There was a significant independent
      association between serum GGT levels and the severity of OSAS. Moreover, serum
      GGT levels were significantly high in patients with cardiovascular disease
      compared with patients without cardiovascular disease in severe-moderate-mild
      OSAS (p < 0.05) and OSAS negative groups while CRP levels were not. This was a
      significant independent association. The present study suggests that high serum
      GGT level, regardless of the other traditional risk factors, is an independent
      predictor of cardiovascular disease in patients with OSAS. The results should be
      confirmed with other randomized prospective studies.

PMID- 21183329
TI  - Electrochemical aptasensor using the tripropylamine oxidation to probe
      intramolecular displacement between target and complementary nucleotide for
      protein array.
AB  - Tripropylamine (TPA) has different oxidation efficiency at double stranded (ds)
      and single stranded (ss)-DNA-modified electrodes. Using this property, a simple
      but sensitive biosensor using TPA oxidation to probe the intramolecular
      displacement was constructed with the analysis of lysozyme as model for the first
      time. After the complementary ss-DNA strand of anti-lysozyme aptamer was
      immobilized onto gold electrode via gold-thiol bond, the incubation with the
      aptamer resulted in the formation of ds-DNA. Lysozyme (in 10 MUL sample) binding
      with aptamer displaced the complementary strand because of the high affinity of
      lysozyme and its aptamer, corresponding to the dissociation of the ds-DNA. The
      modified electrode was swept in 20mM TPA solution from 0.2 to 0.95 V. The
      difference in oxidation current was used to quantify the content of lysozyme with
      a linear range from 1.0 pM to 1.1 nM. That means 10 amol or 6.0 * 10(6) lysozyme
      molecules can be detected. Because the signal is produced from the
      preconcentrated TPA at the electrode surface, the high sensitivity is achieved
      over the single site labelling strategy. The proposed method is simple, stable,
      specific, and time-saving while the complicated sample pre-treatment and the
      labelling to the DNA strand are avoided. The biosensor was validated by the
      analysis of the diluted egg white sample directly. The recovery and
      reproducibility were 93.3-100% and 1.4-4.2%, respectively.

PMID- 21183330
TI  - Sensitive and isothermal electrochemiluminescence gene-sensing of Listeria
      monocytogenes with hyperbranching rolling circle amplification technology.
AB  - Listeria monocytogenes (L. monocytogenes) is one of the most problematic human
      pathogens, as it is mainly transmitted through the food chain and cause
      listeriosis. Thus, specific and sensitive detection of L. monocytogenes is
      required to ensure food safety. In this study, we proposed a method using
      hyperbranching rolling circle amplification (HRCA) combined with magnetic beads
      based electrochemiluminescence (ECL) to offer an isothermal, highly sensitive and
      specific assay for the detection of L. monocytogenes. At first, a linear padlock
      probe was designed to target a specific sequence in the hly gene which is
      specific to L. monocytogenes and then ligated by Taq DNA ligase. After ligation
      and digestion, further amplification by HRCA with a biotiny labeled primer and a
      tris (bipyridine) ruthenium (TBR) labeled primer was performed. The resulting
      HRCA products were then captured onto streptavidin-coated paramagnetic beads and
      were analyzed by magnetic beads based ECL platform to confirm the presence of
      targets. Through this approach, as low as 10 aM synthetic hly gene targets and
      about 0.0002 ng/MUl of genomic DNA from L. monocytogenes can be detected, the
      ability to detect at such ultratrace levels could be attributed to the powerful
      amplification of HRCA and the high sensitivity of current magnetic bead based ECL
      detection platform.

PMID- 21183331
TI  - Botanical micelle and its application for direct electrochemical biosensor.
AB  - This paper is concerned about the entrapment of horseradish peroxidase (HRP)
      within botanical inositol hexakisphosphoric (IP(6)) micelles for the preparation
      of enzyme biosensor. The good affinity of IP(6) micelles with the enzyme provides
      naturally biocompatible microenvironment for the enzyme immobilization, achieving
      the direct electron transfer between HRP and electrode surface. The resulting
      biosensor to H(2)O(2) detection exhibits a low detection limit of 0.1 MUmol L(-1)
      (S/N = 3), a quick response time (3s), and a long-term stability. The apparent
      Michaelis-Menten constant is quite tiny about 0.0016 mmol L(-1).

PMID- 21183332
TI  - Anaesthetic management of a patient with Liddle's syndrome for emergency
      caesarean hysterectomy.
AB  - We describe the anaesthetic management of a patient with Liddle's syndrome during
      caesarean section and emergency hysterectomy for placenta accreta associated with
      significant intrapartum haemorrhage. Liddle's syndrome is a rare autosomal
      dominant disorder characterised by early onset arterial hypertension and
      hypokalaemic metabolic alkalosis. Additional issues were the presence of short
      stature, limb hypertonicity and preeclampsia. Initial management with a low-dose
      combined spinal-epidural technique was subsequently converted to general
      anaesthesia due to patient discomfort. The management of Liddle's syndrome in the
      setting of neuraxial and general anaesthesia in a patient undergoing caesarean
      section is discussed.

PMID- 21183333
TI  - Inadvertent epidural infusion of acetaminophen during labour.

PMID- 21183334
TI  - Caesarean section for twin pregnancy in a parturient with Brugada syndrome.
AB  - Brugada syndrome is a common cause of sudden cardiac death. We report the
      anaesthetic management of a woman with Brugada syndrome for elective caesarean
      section of twins. There are few reports of this disease in pregnancy and we
      believe this is the first of elective caesarean section in a parturient with the
      syndrome. The characteristic electrocardiographic changes of the syndrome are
      linked to sodium channel blockers including local anaesthetics such as
      bupivacaine. The use of bupivacaine for intrathecal central neuraxial blockade as
      well as other drugs commonly used in obstetric anaesthesia is discussed.

PMID- 21183335
TI  - Synthesis of fatty acid methyl ester from used vegetable cooking oil by solid
      reusable Mg 1-x Zn 1+x O2 catalyst.
AB  - Fatty acid methyl ester was produced from used vegetable cooking oil using Mg(1
      )(x) Zn(1+)(x)O(2) solid catalyst and the performance monitored in terms of ester
      content obtained. Used vegetable cooking oil was employed to reduce operation
      cost of biodiesel. The significant operating parameters which affect the overall
      yield of the process were studied. The highest ester content, 80%, was achieved
      with the catalyst during 4h 15 min reaction at 188 degrees C with methanol to oil
      ratio of 9:1 and catalyst loading of 2.55 wt% oil. Also, transesterification of
      virgin oil gave higher yield with the heterogeneous catalyst and showed high
      selectivity towards ester production. The used vegetable cooking oil did not
      require any rigorous pretreatment. Catalyst stability was examined and there was
      no leaching of the active components, and its performance was as good at the
      fourth as at the first cycle.

PMID- 21183336
TI  - Effects of different carbon supplements on phosphorus removal in low C/P ratio
      industrial wastewater.
AB  - This study focuses on the effects of different carbon supplements on biological
      phosphorus removal in the optonics and semiconductor industrial wastewater
      treatment. Experimental results demonstrate that the addition of a carbon source
      (glucose, acetate, and digester supernatant) improved phosphorus removal
      effectively. When the COD/P ratios were controlled in the range of 18-20 (using
      glucose and supernatant as supplement), the acclimated sludge showed more than
      98% removal of phosphorus. In addition, different organic carbons induce
      dissimilar behavior in anaerobic release and aerobic uptake of phosphorus. The
      glucose supplement induces significant phosphorus release in anaerobic phase and
      then an increased phosphorus uptake in aerobic phase. The released phosphorus
      descended in anaerobic phase when acetate and supernatant were added. There was a
      good linear relationship of first order reaction between initial COD
      concentration and specific substrate utilization rate in anaerobic phase.

PMID- 21183338
TI  - Mesophilic batch anaerobic co-digestion of pulp and paper sludge and monosodium
      glutamate waste liquor for methane production in a bench-scale digester.
AB  - This paper presented results from anaerobic co-digestion of pulp and paper sludge
      (PPS) and monosodium glutamate waste liquor (MGWL). A bench-scale anaerobic
      digester, 10 L in volume was developed, to operate under mesophilic (37 +/- 2
      degrees C) batch condition. Under versatile and reliable anaerobic conduct, high
      efficiency for bioconversion of PPS and MGWL were obtained in the system. The
      accumulative methane yield attained to 200 mL g(-1) VS(added) and the peak value
      of methane daily production was 0.5m(3)/(m(3)d). No inhibitions of volatile fatty
      acids (VFAs) and ammonia on anaerobic co-digestion were found. pH 6.0-8.0 and
      alkalinity 1000-4000 mg CaCO(3)/L were got without adjustment. This work showed
      that there was a good potential to the use of PPS and MGWL to anaerobic co
      digestion for methane production.

PMID- 21183337
TI  - Sequential production of two biopolymers-levan and poly-epsilon-lysine by
      microbial fermentation.
AB  - Sequential fermentation for the production of two invaluable biopolymers, levan
      and poly-epsilon-lysine (epsilon-PL), has been successfully developed. It
      involves fermentation of Bacillus subtilis (natto) Takahashi in sucrose medium to
      produce levan, separation of levan product from small remaining sugar molecules
      by ultrafiltration and fermentation of the remnant from levan production by
      Streptomyces albulus to produce epsilon-PL. In the process, 50-60 g/L of levan
      was produced (100% recovery after precipitation by ethanol). The remnant from
      levan production with glucose adjusted to 30 g/L and with combined use of yeast
      extract (10 g/L), (NH(4))(2)SO(4) (2g/L) and basal salts was proven to be
      suitable for epsilon-PL production. 4.37 g/L of epsilon-PL accumulation (85%
      recovery after purification) was reached in 72 h using two-stage fermentation
      with control of pH. The process of using remnant (waste) from levan fermentation
      for the second biopolymer (epsilon-PL) production is unprecedented and the
      products obtained are environmental-friendly.

PMID- 21183339
TI  - Nitrogen mass balances for pilot-scale biofilm stabilization ponds under tropical
      conditions.
AB  - Nitrogen removal in biofilm waste stabilization ponds were modeled using nitrogen
      mass balance equations. Four pilot-scale biofilm maturation ponds were
      constructed in Uganda. Pond 1 was control; the others had 15 baffles in each of
      them. Two loading conditions were investigated (period 1, 18.2g and period 2,
      26.8 g NH(4)-Nd(-1)). Total nitrogen and TKN mass balances were made. Bulk water
      and biofilm nitrification rates were determined and used in the TKN mass balance.
      Results for total nitrogen mass balance showed that for both periods,
      denitrification was the major removal mechanism. Nitrogen uptake by algae was
      more important during period 1 than in period 2. The TKN mass balance predicted
      well effluent TKN for period 2 than period 1. This could be due to fluctuations
      in algae density and ammonia uptake during period 1, no conclusions on
      reliability of mass balance model in period 1 was made.

PMID- 21183340
TI  - Enhanced algae growth in both phototrophic and mixotrophic culture under blue
      light.
AB  - Biomass productivity and fatty acid methyl esters (FAME) derived from
      intracellular lipid of a Nannochloropsis sp. isolated from Singapore's coastal
      waters were studied under different light wavelengths and intensities.
      Nannochloropsis sp., was grown in both phototrophic and mixotrophic (glycerol as
      the carbon source) culture conditions in three primary monochromatic light
      wavelengths, i.e., red, green and blue LEDs, and also in white LED. The maximum
      specific growth rate (MU) for LEDs was blue>white>green>red. Nannochloropsis sp.
      achieved a MU of 0.64 and 0.66 d(-1) in phototrophic and mixotrophic cultures
      under blue lighting, respectively. The intracellular fatty acid composition of
      Nannochloropsis sp. varied between cultures exposed to different wavelengths,
      although the absolute fatty acid content did differ significantly. Maximum FAME
      yield from Nannochloropsis sp. was 20.45% and 15.11% of dry biomass weight
      equivalent under photo- and mixotrophic culture conditions respectively for
      cultures exposed to green LED (550 nm). However, maximum volumetric FAME yield
      was achieved for phototrophic and mixotrophic cultures (i.e., 55.13 and 111.96
      mg/l, respectively) upon cell exposure to blue LED (470 nm) due to highest
      biomass productivity. It was calculated that incremental exposure of light
      intensity over the cell growth cycle saves almost 20% of the energy input
      relative to continuous illumination for a given light intensity.

PMID- 21183341
TI  - 2-Hydroxycurcuminoid induces apoptosis of human tumor cells through the reactive
      oxygen species-mitochondria pathway.
AB  - 2-Hydroxycinnamaldehyde (HCA) and curcumin have been reported to have antitumor
      effects against various human tumor cells in vitro and in vivo by generation of
      ROS. Aldehyde-free HCA analogs were synthesized based on the structure of
      curcumin, which we have called 2-hydroxycurcuminoids. The hydroxyl group of
      curcuminoids enhances the ability to generate ROS. 2-Hydroxycurcuminoid (HCC-7)
      strongly inhibited the growth of SW620 colon tumor cells with a GI(50) value of
      7MUM, while the parent compounds, HCA and curcumin, displayed GI(50) values of 12
      and 30MUM, respectively. HCC-7 was found to induce apoptosis through the reactive
      oxygen species-mitochondria pathway and cell cycle arrest at G2/M phase.

PMID- 21183342
TI  - Discovery of novel hepatoselective HMG-CoA reductase inhibitors for treating
      hypercholesterolemia: a bench-to-bedside case study on tissue selective drug
      distribution.
AB  - The design of drugs with selective tissue distribution can be an effective
      strategy for enhancing efficacy and safety, but understanding the translation of
      preclinical tissue distribution data to the clinic remains an important
      challenge. As part of a discovery program to identify next generation liver
      selective HMG-CoA reductase inhibitors we report the identification of (3R,5R)-7
      (4-((3-fluorobenzyl)carbamoyl)-5-cyclopropyl-2-(4-fluorophenyl)-1H-imidazol-1-yl)
      3,5-dihydroxyheptanoic acid (26) as a candidate for treating hypercholesterlemia.
      Clinical evaluation of 26 (PF-03491165), as well as the previously reported 2 (PF
      03052334), provided an opportunity for a case study comparison of the preclinical
      and clinical pharmacokinetics as well as pharmacodynamics of tissue targeted HMG
      CoA reductase inhibitors.

PMID- 21183343
TI  - A novel transition state analog inhibitor of guanase based on azepinomycin ring
      structure: Synthesis and biochemical assessment of enzyme inhibition.
AB  - Synthesis and biochemical inhibition studies of a novel transition state analog
      inhibitor of guanase bearing the ring structure of azepinomycin have been
      reported. The compound was synthesized in five-steps from a known compound and
      biochemically screened against the rabbit liver guanase. The compound exhibited
      competitive inhibition profile with a K(i) of 16.7+/-0.5MUM.

PMID- 21183345
TI  - Non-covalent inhibitors of rhinovirus 3C protease.
AB  - The first known non-covalent inhibitors of rhinovirus 3C protease (3CP) have been
      identified through fragment based screening and hit identification activities.

PMID- 21183344
TI  - Discovery of molecular switches within the ADX-47273 mGlu5 PAM scaffold that
      modulate modes of pharmacology to afford potent mGlu5 NAMs, PAMs and partial
      antagonists.
AB  - This Letter describes a chemical lead optimization campaign directed at a weak
      mGlu(5) NAM discovered while developing SAR for the mGlu(5) PAM, ADX-47273. An
      iterative parallel synthesis effort discovered multiple, subtle molecular
      switches that afford potent mGlu(5) NAMs, mGlu(5) PAMs as well as mGlu(5) partial
      antagonists.

PMID- 21183346
TI  - A case of adult Pompe disease presenting with severe fatigue and selective
      involvement of type 1 muscle fibers.
AB  - We present a case of adult Pompe disease (acid maltase deficiency) with an
      uncommon clinical presentation characterized by severe fatigue and myalgia prior
      to the onset of limb girdle weakness. Remarkably, the muscle biopsy demonstrated
      selective involvement of type 1 muscle fibers. The cause and clinical effects of
      fiber type specific involvement are currently unknown, but the phenomenon might
      contribute to the clinical heterogeneity in Pompe disease and the variable
      response to enzyme replacement therapy.

PMID- 21183347
TI  - Rational use of trastuzumab in metastatic and locally advanced breast cancer:
      implications of recent research.
AB  - The management of HER2-positive metastatic breast cancer, a disease renowned for
      its aggressive natural history, has been revolutionized by the introduction of
      trastuzumab. Indeed, outcomes for patients with HER2-positive advanced breast
      cancer are now equivalent to, if not better than, those of their HER2-negative
      counterparts. Since the pivotal registration trial, a wealth of new clinical data
      has emerged regarding the use of trastuzumab in a variety of clinical contexts -
      adding to the evidence but also highlighting areas of uncertainly and debate.
      These include the optimal partner chemotherapy(ies) to trastuzumab; the
      effectiveness of combining trastuzumab with endocrine therapy; the benefits of
      continuing trastuzumab after progression on a trastuzumab-containing regimen; and
      the role of trastuzumab in locally advanced and inflammatory breast cancer. In
      this paper we review major clinical trials addressing these questions, clinical
      recommendations that can be made as a result, and the strength of evidence that
      supports them. Finally, we identify areas of ongoing uncertainty, and propose
      recommendations for future research in this field.

PMID- 21183348
TI  - Transport according to GARP: receiving retrograde cargo at the trans-Golgi
      network.
AB  - Tethering factors are large protein complexes that capture transport vesicles and
      enable their fusion with acceptor organelles at different stages of the
      endomembrane system. Recent studies have shed new light on the structure and
      function of a heterotetrameric tethering factor named Golgi-associated retrograde
      protein (GARP), which promotes fusion of endosome-derived, retrograde transport
      carriers to the trans-Golgi network (TGN). X-ray crystallography of the Vps53 and
      Vps54 subunits of GARP has revealed that this complex is structurally related to
      other tethering factors such as the exocyst, the conserved oligomeric Golgi (COG)
      and Dsl1 (dependence on SLY1-20) complexes, indicating that they all might work
      by a similar mechanism. Loss of GARP function compromises the growth, fertility
      and/or viability of the defective organisms, emphasizing the essential nature of
      GARP-mediated retrograde transport.

PMID- 21183349
TI  - Chaperoning osteogenesis: new protein-folding disease paradigms.
AB  - Recent discoveries of severe bone disorders in patients with deficiencies in
      several endoplasmic reticulum chaperones are reshaping the discussion of type I
      collagen folding and related diseases. Type I collagen is the most abundant
      protein in all vertebrates and a crucial structural molecule for bone and other
      connective tissues. Its misfolding causes bone fragility, skeletal deformity and
      other tissue failures. Studies of newly discovered bone disorders indicate that
      collagen folding, chaperones involved in the folding process, cellular responses
      to misfolding and related bone pathologies might not follow conventional protein
      folding paradigms. In this review, we examine the features that distinguish
      collagen folding from that of other proteins and describe the findings that are
      beginning to reveal how cells manage collagen folding and misfolding. We discuss
      implications of these studies for general protein folding paradigms, unfolded
      protein response in cells and protein folding diseases.

PMID- 21183350
TI  - Minimal detectable change for gait variables collected during treadmill walking
      in individuals post-stroke.
AB  - Post-stroke gait impairments are common and result in slowed walking speeds and
      decreased community participation post-stroke. Treadmill training has recently
      emerged as an effective gait rehabilitation intervention. Furthermore, kinematic
      and kinetic data collected during treadmill walking are commonly used for
      assessing gait performance. The minimal detectable change (MDC) for gait
      variables provides a useful index to determine whether the magnitude of change in
      gait produced after an intervention is greater than the amount of change
      attributable to day-to-day variability in gait or test-retest measurement errors.
      The MDC values for kinematic, ground reaction force (GRF), spatial, and temporal
      variables collected during treadmill walking post-stroke have not been previously
      reported. The objective of this study was, therefore, to compute MDCs for post
      stroke gait kinematics, GRF indices, temporal, and spatial measures during
      treadmill walking. Nineteen individuals with chronic post-stroke hemiparesis (12
      males; age=47-75 years; 72.6+/-63.4 months since stroke) participated in 2
      testing sessions separated by 20.7+/-26.8 days. Our results showed that test
      retest reliability was excellent for all gait variables tested (intraclass
      correlation coefficients=0.799-0.986). MDCs were reported for hip, knee, and
      ankle joint angles (range 3.8 degrees  for trailing limb angles to 11.5 degrees 
      for hip extension), peak anterior GRF (2.85% body weight), mean vertical GRF
      (4.65% body weight), all temporal variables (range 3.2-4.2% gait cycle), and
      paretic step length (6.7 cm). These MDCs provide a useful reference to help
      interpret the magnitudes of changes in post-stroke gait variables.

PMID- 21183351
TI  - Combined effects of fast treadmill walking and functional electrical stimulation
      on post-stroke gait.
AB  - Gait dysfunctions are highly prevalent in individuals post-stroke and affect
      multiple lower extremity joints. Recent evidence suggests that treadmill walking
      at faster than self-selected speeds can help improve post-stroke gait
      impairments. Also, the combination of functional electrical stimulation (FES) and
      treadmill training has emerged as a promising post-stroke gait rehabilitation
      intervention. However, the differential effects of combining FES with treadmill
      walking at the fast versus a slower, self-selected speed have not been compared
      previously. In this study, we compared the immediate effects on gait while post
      stroke individuals walked on a treadmill at their self-selected speed without FES
      (SS), at the SS speed with FES (SS-FES), at the fastest speed they are capable of
      attaining (FAST), and at the FAST speed with FES (FAST-FES). During SS-FES and
      FAST-FES, FES was delivered to paretic ankle plantarflexors during terminal
      stance and to paretic dorsiflexors during swing phase. Our results showed
      improvements in peak anterior ground reaction force (AGRF) and trailing limb
      angle during walking at FAST versus SS. FAST-FES versus SS-FES resulted in
      greater peak AGRF, trailing limb angle, and swing phase knee flexion. FAST-FES
      resulted in further increase in peak AGRF compared to FAST. We posit that the
      enhancement of multiple aspects of post-stroke gait during FAST-FES suggest that
      FAST-FES may have potential as a post-stroke gait rehabilitation intervention.

PMID- 21183352
TI  - Quantification of age- and gender-related changes in diffusion tensor imaging
      indices in deep grey matter of the normal human brain.
AB  - This study aimed to demonstrate age-related and gender-related changes in
      diffusion tensor imaging (DTI) indices of deep grey matter (GM) nuclei of the
      normal human brain. DTI was performed on 142 subjects (age: 10-52 years). Regions
      of interest were placed on the caudate nucleus (CN), putamen, globus pallidus,
      frontal white matter (WM), occipital WM, anterior and posterior limb of internal
      capsule, genu of the corpus callosum and splenium in all participants. The
      quadratic regression model was used to describe age-related and gender-related
      changes in DTI indices for GM and WM. We observed increased fractional anisotropy
      (FA) values with age up to adulthood in GM, and a rise up to the third decade of
      life followed by a decrease in FA for WM. We observed higher FA values in males
      compared to females in CN and all WM regions. Decreased mean diffusivity with age
      was observed in GM and WM irrespective of gender. This normative data may be
      valuable in the diagnosis of neurodegenerative diseases.

PMID- 21183353
TI  - Investigation of alpha-phenylnorstatine and alpha-benzylnorstatine as transition
      state isostere motifs in the search for new BACE-1 inhibitors.
AB  - Inhibition of the BACE-1 protease enzyme has over the recent decade developed
      into a promising drug strategy for Alzheimer therapy. In this report, more than
      20 new BACE-1 protease inhibitors based on alpha-phenylnorstatine, alpha
      benzylnorstatine, iso-serine, and beta-alanine moieties have been prepared. The
      inhibitors were synthesized by applying Fmoc solid phase methodology and
      evaluated for their inhibitory properties. The most potent inhibitor, tert
      alcohol containing (R)-12 (IC(50)=0.19MUM) was co-crystallized in the active site
      of the BACE-1 protease, furnishing a novel binding mode in which the N-terminal
      amine makes a hydrogen bond to one of the catalytic aspartic acids.

PMID- 21183354
TI  - Synthesis and in vitro anti-hepatitis B virus activity of six-membered
      azanucleoside analogues.
AB  - Fifteen novel six-membered azanucleoside derivatives were prepared and evaluated
      for their anti-hepatitis B virus (HBV) activity and cytotoxicity in human
      hepatoblastoma-derived liver Hep-G2 cells. The most potent compound 16b with an
      IC(50) value of 2.74MUg/mL (lower than 3TC) and a SI value of 13.5 was disclosed.
      The key synthetic steps involved the rearrangement of lactones (which were
      readily obtained from monosaccharides) and the Lewis acid-catalyzed condensation
      of nucleobases with azasugar donors. Using the versatile acetylated azasugar
      donors, azanucleosides covering three types of azasugars and four types of
      natural nucleobases were successfully obtained. The experimental results showed
      that some six-membered azanucleosides may find applications in the discovery of
      new anti-viral agents.

PMID- 21183355
TI  - Synthesis and evaluation of beta-carboline derivatives as potential monoamine
      oxidase inhibitors.
AB  - Previous studies have shown that harmine is a reversible inhibitor of human
      monoamine oxidase A (MAO-A). Moreover, the crystal structure of human MAO-A in
      complex with harmine has been recently solved. This crystal structure shows that
      close to the methoxy group of the harmine moiety, a lipophilic pocket is left
      vacant within the binding site of human MAO-A. Our objective was to optimize the
      beta-carboline series against human MAO-A in order to explore this pocket.
      Therefore, a series of beta-carboline derivatives has been synthesized. The
      compounds were evaluated for their human monoamine oxidase A and B inhibitory
      potency and their K(i) values were estimated. The results show that O-alkylated
      compounds with lipophilic groups like cyclohexyl, phenyl and aliphatic chains
      increase the inhibition of MAO-A compared to harmine. Compound 3e, with the
      trifluorobutyloxy group, was the most active of this series, with a K(i) against
      MAO-A of 3.6nM. Molecular docking studies show that the trifluorobutyloxy chain
      occupies the hydrophobic pocket vacant with harmine. The O-alkylated compounds
      are less active on MAO-B than on MAO-A. However, several compounds show a better
      inhibition on MAO-B compared to harmine. Compound 3f, with the cyclohexylmethoxy
      chain, displayed the best inhibitory activity against MAO-B with a K(i) value of
      221.6nM. This cyclohexyl bearing analogue is also a potent MAO-A inhibitor with a
      K(i) value of 4.3nM. Molecular docking studies show that the cyclohexyl chain
      also occupies a hydrophobic pocket but in different ways in MAO-A or MAO-B.

PMID- 21183356
TI  - A rare constellation of empyema, lung abscess, and mediastinal abscess as a
      complication of endobronchial ultrasound-guided transbronchial needle aspiration.
AB  - The introduction of endobronchial ultrasound-guided transbronchial needle
      aspiration (EBUS-TBNA) brought about significant advancement in the field of
      bronchoscopy. The major indications for EBUS-TBNA are lung cancer staging and
      diagnosis of mediastinal lymphadenopathy. This procedure is minimally invasive
      and cost saving, and no complications have been described in large-scale studies.
      In this report, we present a case of empyema, lung abscess, and mediastinal
      abscess that developed in a patient undergoing EBUS-TBNA; the patient
      subsequently recovered uneventfully after aggressive surgical debridement and
      antimicrobial therapy.

PMID- 21183357
TI  - The SOURCE Registry: what is the learning curve in trans-apical aortic valve
      implantation?
AB  - OBJECTIVE: Trans-apical aortic valve implantation (TA-AVI) has been shown to be a
      reproducible technique. Early results from the SAPIEN Aortic Bioprosthesis
      European Outcome (SOURCE) Registry identified major access complications
      associated with high 30-day mortality. Using the SOURCE Registry, we analyze the
      learning curve for TA-AVI over the first 2 years after commercialization.
      METHODS: The SOURCE Registry gathered data for 2 consecutive years at European
      centers following commercialization of the Edwards SAPIEN bioprosthesis, totaling
      2339 patients (1038 in COHORT 1 and 1301 in COHORT 2). Only data from centers
      that provided all of their consecutively treated patients were included in this
      study. We compared the 30-day results of TA-AVI from COHORT 1 (C-1: January/2008
      January/2009) with the 30-day results of COHORT 2 (C-2: February/2009
      January/2010). RESULTS: This analysis is based on a total number of 575 TA-AVIs
      in C-1 and 819 TA-AVIs in C-2. Mean age (C-1: 80.7 years, C-2: 80.5 years) and
      logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) (C-1:
      29.1%, C-2 27.3%) were not significantly different. Valve malposition (C-1: 1.6%,
      C-2: 1.2%), valve migration/embolization (C-1: 0.5%, C-2: 1.0%), and major access
      complications (C-1: 2.1%, C-2: 1.8%) were in total less frequent, but not
      statistically significant lower in C-2. However, the reduction of aortic
      regurgitation >2+ immediately following the procedure (C-1: 4.52%, C-2: 2.1%,
      p=0.011) and conversion rate to open surgery (C-1: 3.7%, C-2: 1.5%, p=0.0315)
      reached statistical significance. Postoperative complications included dialysis
      (C-1: 7.0%, C-2: 5.7%, p=ns), pacemaker implantation (C-2: 7.7%, C-2: 6.7%,
      p=ns), stroke (C-1: 2.4%, C-2: 2.6%, p=ns), and myocardial infarct (C-1: 0.7%, C
      2: 0.4%, p=ns). The total 30-day mortality was 10.8% and not significantly
      different between the two groups (C-1: 10.8%, C-2: 10.7%, p=ns). CONCLUSIONS:
      Although the incidence of technical intra procedural complications has trended
      downward, reflecting the learning curve for TA-AVI, 30-day mortality was
      unchanged, likely due to patient co-morbidities not captured by preoperative risk
      variables.

PMID- 21183358
TI  - The role of non-human primates in the neurological safety of live viral vaccines
      (review).
AB  - This review covers comprehensive data accumulated during the long history of
      using monkeys in the determination of neurovirulence activity and safety of live
      poliomyelitis, flaviviral, smallpox and mumps vaccines, as well as newly
      developed transgenic mouse and molecular-biological tests. The review also
      analyzes processes caused by some of these viruses in infant rodents (mice, rats)
      and evaluates the role of these processes in vaccine safety control.
      Recommendations resulting from this analysis are presented.

PMID- 21183359
TI  - How to quantify inflammatory tissue reactions following embolization?

PMID- 21183360
TI  - Uterine artery embolization in the treatment of postpartum uterine hemorrhage.
AB  - PURPOSE: To evaluate the clinical effectiveness and safety of uterine artery
      embolization (UAE) in the treatment of primary postpartum hemorrhage (PPH),
      secondary PPH, and PPH associated with cesarean section. MATERIALS AND METHODS:
      All women who underwent UAE for obstetric-related hemorrhage during a 52-month
      period culminating in April 2009 were included. Clinical success was defined as
      obviation of hysterectomy. Blood product requirements before and after UAE were
      calculated. Statistically significant associations between subject
      characteristics and clinical success were evaluated. The two subgroups of women
      with uterine artery pseudoaneurysms and women who underwent cesarean section were
      examined separately as well. RESULTS: Sixty-six women (mean age, 33 years; range,
      17-47 y) underwent UAE, with an overall clinical success rate of 95% (98% for
      primary PPH, 88% for secondary PPH, and 94% for PPH associated with cesarean
      section) and an overall complication rate of 4.5%. Mean pre- and postembolization
      transfusion requirements were 3.1 U and 0.4 U of packed red blood cells,
      respectively. The only significant characteristic identified for the cases that
      necessitated hysterectomy was an increased transfusion requirement after UAE
      (increase of 1.0 U +/- 0.5; P = .02). Uterine artery pseudoaneurysms were
      associated with secondary PPH (P = .01) and cesarean section (P = .03).
      CONCLUSIONS: The threshold for UAE in women with PPH should be low, as it is
      associated with a high clinical effectiveness rate and a low complication rate.
      Uterine artery pseudoaneurysms should be suspected in women presenting with
      secondary PPH after cesarean section.

PMID- 21183361
TI  - Utility of left ventricular systolic torsion derived from 2-dimensional speckle
      tracking echocardiography in monitoring acute cellular rejection in heart
      transplant recipients.
AB  - BACKGROUND: Reduced left ventricular torsion (LV-tor) has been reported to be
      associated with acute rejection in heart transplant (HTx) recipients. We
      investigated the utility of LV-tor analysis derived from 2-dimensional speckle
      tracking echocardiography (2D-STE) for detecting allograft rejection. METHODS: A
      total of 301 endomyocardial biopsies (EMBs), right heart catheterizations and
      echocardiograms were performed in 32 HTx recipients. Echocardiography was done
      within 3 hours from EMB or simultaneously with the procedures. The LV-tor was
      defined as the difference between apical and basal end-systolic rotations. The LV
      tor values with and without cellular rejection were compared. In addition, we
      investigated whether the change in LV-tor values predicts the change in rejection
      grade in each patient. The baseline LV-tor value in each patient was defined as a
      mean value of the first 3 LV-tor measurements obtained when the patient was free
      from rejection. RESULTS: According to the conventional International Society for
      Heart and Lung Transplantation criteria, 274 biopsies showed a rejection Grade of
      0, 1a or 1b (Group AR(-)), whereas 27 biopsies were Grade 2 or higher (Group
      AR(+)). LV-tor decreased more in Group AR(+) than in Group AR(-) (9.3 +/- 0.7 vs
      12.2 +/- 0.2 degrees, p < 0.0001). In the LV-tor measurement for each patient,
      the 25% reduction in LV-tor value from baseline predicted Grade 2 or higher
      rejection with a predictive accuracy of 92.9%. CONCLUSION: LV-tor derived from 2D
      STE could be of clinical value for non-invasive monitoring of acute rejection in
      HTx recipients.

PMID- 21183362
TI  - Advances in heart transplantation: the year in review.
AB  - Although the world of advanced heart failure has intensely focused its spotlight
      on mechanical circulatory support, the field of heart transplantation has
      continued to evolve. We highlight the latest clinical and laboratory research
      that have affected the field of adult heart transplantation. Major scientific and
      clinical advances in the field of heart transplantation have focused on expanding
      the donor pool, refining the use of immunosuppression, and monitoring the effects
      of therapy.

PMID- 21183363
TI  - Seizure induced cardiac asystole in epilepsy patients undergoing long term video
      EEG monitoring.
AB  - Ictal-related cardiac asystole is supposed to be a risk factor for sudden
      unexpected death in epilepsy (SUDEP). We retrospectively analyzed the occurrence
      of ictal asystole in 2003 epilepsy patients undergoing long-term video EEG/ECG
      monitoring from 1/1999 to 6/2010 at the Freiburg epilepsy centre. Seven patients
      had cardiac arrest with a duration of at least 3s; 6 ictal, one postictal. In all
      patients, the temporal lobe was involved in ictal activity based on
      neurophysiological investigations or morphological lesion. Whereas asystole was
      self-limited in six cases, one patient with insular seizure origin had to undergo
      cardiopulmonary resuscitation. Interestingly, also patients with a short history
      of epilepsy, low seizure frequency and under treatment in monotherapy showed
      episodes of asystole. In all cases, even with brief cardiac arrest, asystole was
      associated with subsequent EEG flattening. In conclusion, ictal asystole is a
      rare event even in a population undergoing major changes in antiepileptic
      medication. Temporal lobe epilepsy was associated with a risk for asystole;
      cardiac arrest also occurred in patients who, based on their history, might have
      not been considered at elevated risk for SUDEP.

PMID- 21183364
TI  - Elderly patients with epileptic seizures: in-patient observational study of two
      French community hospitals.
AB  - Epileptic seizures (ESs) in the elderly are recognized as frequent, and
      potentially difficult to diagnose. Their clinical features and relevant
      diagnostic problems still remain poorly investigated in hospital populations
      outside the setting of tertiary referral centres. In this study we attempted to
      improve the understanding of these aspects in community institutions. We
      conducted a four-year retrospective observational study of 104 consecutive
      elderly patients with the diagnosis of ES, in 2 French community hospitals. Most
      ESs were partial (n=50; 48.07%) but generalized ESs were also clinically frequent
      (n=41; 39.42%). Brain imaging was highly contributive for the diagnosis of
      partial ESs by demonstrating causative focal structural lesions. ESs were often
      unprovoked (n=82; 78.84%). Fifty six of these (68.29%) were symptomatic. Stroke
      lesions were the most identified cause (n=17; 20.73%). In 26 patients (31.70%)
      aetiology was unknown. Various diagnostic problems were identified. Inter
      observer agreement between neurologists and non-neurologists based on clinical
      judgement was only "fair" (kappa coefficient: 0.28; 95% CI; p=0.002). ESs were
      initially misdiagnosed in 28 patients (26.92%). The misdiagnosis rate was higher
      among non-neurologists (n=25; 89.28%) as compared to neurologists (n=8; 28.57%)
      (p<0.0001). The presence of focal neurological abnormalities was an important
      diagnostic indicator of a positive diagnosis of ES. In conclusion, ESs in the
      elderly are generally partial, unprovoked and symptomatic, and caused by stroke
      related lesions. Many are still overlooked, highlighting the important role of
      specialist input and rigorous clinical evaluation for diagnostic confirmation.

PMID- 21183365
TI  - The effects of 5alpha-reductase inhibition on benign prostatic hyperplasia
      treated by photoselective vaporization prostatectomy with the 120 Watt GreenLight
      HPS laser system.
AB  - BACKGROUND: We sought to determine whether the efficacy and efficiency of 120W
      GreenLight HPS (American Medical Systems, Inc) laser photoselective vaporization
      prostatectomy (PVP) is compromised in patients on chronic 5alpha-reductase
      inhibitor (RI) therapy. STUDY DESIGN: Our GreenLight HPS laser PVP experience in
      patients with and without long-term 5alphaRI was evaluated. American Urological
      Association Symptom Score (AUASS), quality of life (QoL) score, maximum urinary
      flow rate (Qmax), and postvoid residual (PVR) were measured preoperatively and at
      1 and 4 weeks and at 3, 6, 12, 18, and 24 months postsurgery. PSA values and
      transrectal ultrasonography (TRUS) prostate volumes were determined
      preoperatively and at 3 months postsurgery. RESULTS: Fifty-seven patients were on
      either dutasteride or finasteride (5alphaRI+) and 124 were not (5alphaRI-). Mean
      prostate volumes were 67.1 +/- 35.3 mL and 69.2 +/- 41.9 mL (p = 0.646) and mean
      PSA values were 2.2 +/- 2.4 ng/mL and 2.7 +/- 2.6 ng/ml (p = 0.289),
      respectively. There were no significant differences in the parameters of laser
      use (13.6 +/- 9.2 minutes and 13.4 +/- 10.4 minutes, p = 0.965) and energy usage
      (87.1 +/- 62.4 kJ and 91.8 +/- 69.6 kJ, p = 0.623). The majority of patients were
      catheter-free at discharge for this wholly outpatient procedure. AUASS, QoL, and
      Qmax values showed significant improvement within each group (p < 0.05). Compared
      with baseline, PVR values improved in both groups but did not decrease
      significantly in 5alphaRI+ (p > 0.05). There was no significant difference in the
      degree of improvement between the 2 groups in all parameters (AUASS, QoL, Qmax,
      PVR, PSA, and TRUS volume). CONCLUSIONS: The efficacy and efficiency of PVP with
      the GreenLight HPS laser are not negatively affected in patients on chronic
      5alphaRI therapy.

PMID- 21183366
TI  - Impaired alcohol metabolism after gastric bypass surgery: a case-crossover trial.
AB  - BACKGROUND: Severe obesity remains the leading public health crisis of the
      industrialized world, with bariatric surgery the only effective and enduring
      treatment. Poor psychological adjustment has been occasionally reported
      postoperatively. In addition, evidence suggests that patients can metabolize
      alcohol differently after gastric bypass. STUDY DESIGN: Preoperatively and at 3
      and 6 months postoperatively, 19 Roux-en-Y gastric bypass (RYGB) patients' breath
      alcohol content (BAC) was measured every 5 minutes after drinking 5 oz red wine
      to determine peak BAC and time until sober in a case-crossover design
      preoperatively and at 6 months postoperatively. RESULTS: Patients reported
      symptoms experienced when intoxicated and answered a questionnaire of drinking
      habits. The peak BAC in patients after RYGB was considerably higher at 3 months
      (0.059%) and 6 months (0.088%) postoperatively than matched preoperative levels
      (0.024%). Patients also took considerably more time to return to sober at 3
      months (61 minutes) and 6 months (88 minutes) than preoperatively (49 minutes).
      Postoperative intoxication was associated with lower levels of diaphoresis,
      flushing, and hyperactivity and higher levels of dizziness, warmth, and double
      vision. Postoperative patients reported drinking considerably less alcohol, fewer
      preferred beer, and more preferred wine than before surgery. CONCLUSIONS: This is
      the first study to match preoperative and postoperative alcohol metabolism in
      gastric bypass patients. Post-RYGB patients have much higher peak BAC after
      ingesting alcohol and require more time to become sober. Patients who drink
      alcohol after gastric bypass surgery should exercise caution.

PMID- 21183367
TI  - Operation compared with watchful waiting in elderly male inguinal hernia
      patients: a review and data analysis.

PMID- 21183368
TI  - In vitro effects of detergent sclerosants on clot formation and fibrinolysis.
AB  - OBJECTIVE: To investigate the in vitro effects of detergent sclerosants sodium
      tetradecyl sulphate (STS) and polidocanol (POL) on clot formation and lysis.
      MATERIALS AND METHODS: clot kinetics were assessed in whole blood by
      thromboelastography (TEG(r)) and rotational thromboelastometry (ROTEM(r)).
      Fibrinogen was measured by the Clauss method in plasma and factor XIII (FXIII) by
      enzyme-linked immunosorbent assay (ELISA). Turbidity measurements were used to
      assess clot lysis in plasma, and fibrinolysis in non-cross-linked and cross
      linked fibrin. D-dimer was measured by VIDAS(r), STA(r)Liatest(r) and AxSYM(r)
      assays. RESULTS: Strong clots were formed at low sclerosant concentrations (0.075
      0.1%). At midrange concentrations (0.15% STS, 0.15-0.3% POL), both agents
      inhibited the contribution of platelets to clot firmness and formed weak clots
      prone to lysis. At higher concentrations (STS >= 0.3% and POL >= 0.6%), clot
      formation was inhibited. STS destroyed FXIII at >= 0.15% and fibrinogen at >=
      0.6%. Neither sclerosant had a significant effect on cross-linked fibrin, but STS
      had a lytic effect on non-cross-linked fibrin. STS caused an artefactual
      elevation of D-dimer in the VIDAS(r) assay when fibrinogen was present.
      CONCLUSION: Detergent sclerosants demonstrated a trimodal effect on clot
      formation, initiating strong clots at low concentrations, weak clots at midrange
      concentrations and preventing clot formation at higher concentrations. Neither
      agent had fibrinolytic activity.

PMID- 21183369
TI  - Triglyceride to HDL ratio is a reliable predictor of adverse outcomes in risk
      stratification for candidates undergoing abdominal aortic surgery.
AB  - INTRODUCTION: The aim of this study was to establish if an elevated triglyceride
      to high-density lipoprotein (HDL) ratio (THR) is not only a risk factor for
      cardiovascular and overall morbidity as the updated evidence shows, but could
      also be employed as a significant predictor for surgical adverse outcomes and
      hence be a valid tool for risk stratification of candidates undergoing abdominal
      aortic surgery. METHODS: This is a single-centre retrospective analysis of 2224
      patients who underwent open abdominal aortic surgery between January 1996 and
      2009. This cohort was divided into quartiles of THR. A list of covariates has
      been entered with THR into a multiple logistic model with forwards stepwise
      selection. The obtained result is an adjusted model, conceived to establish the
      association between THR and perioperative adverse events. Discrimination of the
      model so obtained and comparison with vascular-specific risk stratification
      scoring systems were evaluated using the area under the receiver operating
      characteristic (AUROC). RESULTS: THR had the highest predictive value for the
      outcomes of interest. The adjusted odds ratios (ORs) per every 0.1 augmentation
      of THR were 1.41 (1.08-1.88) for cardiac, 1.38 (1.09-1.84) for respiratory, 1.27
      (1.06-1.54) for renal adverse events and 1.02 (0.84-1.23) for mortality.
      Regarding mortality, either of the scoring systems Vascular Physiological and
      Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM)
      and customised probability index (CPI) and the THR ranked as moderate
      discriminators, with THR performing the worst (AUROC 0.71) compared with Vascular
      POSSUM (AUROC 0.76) and CPI (AUROC 0.78). THR performed as a very strong
      predictor of morbidity (AUROC 0.86), ranking above Vascular POSSUM (AUROC 0.72).
      CONCLUSIONS: THR is a significant predictor of perioperative morbidity and
      mortality. THR offers a broad outlook on the metabolic state of patients
      undergoing major abdominal aortic surgery and hence their propensity to adverse
      events, allowing us to risk-stratify the prognostic outcome of surgical
      intervention and possibly intervene preoperatively to optimise results.

PMID- 21183370
TI  - The anticonvulsant levetiracetam for the treatment of pain in polyneuropathy: a
      randomized, placebo-controlled, cross-over trial.
AB  - Levetiracetam is an anticonvulsant which is assumed to act by modulating
      neurotransmitter release via binding to the vesicle protein SV2A. This could have
      an impact on signaling in the nociceptive system, and a pilot study indicated
      relief of neuropathic pain with levetiracetam. OBJECTIVES: The aim of this study
      was to test the analgesic effect of levetiracetam in painful polyneuropathy.
      METHODS: This was a randomized, double-blind, placebo-controlled, cross-over
      trial with levetiracetam 3000 mg/day versus placebo (6-week treatment periods).
      Patients with diagnosed polyneuropathy and symptoms for more than 6 months, age
      between 20 and 80 years, pain intensity of more than 4 on a 0-10-point numeric
      rating scale, and pain at least 4 days a week were included in the study. The
      primary outcome measure was pain relief at the end of each treatment period as
      measured on a 6-point verbal scale. RESULTS: Ninety-three patients were screened
      for participation and 39 patients entered the study. Thirty-five patients were
      included in the data analysis. There were no differences in the ratings of pain
      relief (levetiracetam 2.29 versus placebo 2.28, p=0.979), total pain intensity
      (levetiracetam 5.5 versus placebo 5.3, p=0.293) or any of the other outcome
      measures (p=0.147-1.00). CONCLUSION: This study indicates that the anticonvulsant
      levetiracetam has no clinically relevant effect on painful polyneuropathy.

PMID- 21183371
TI  - Autism associated with low 5-hydroxyindolacetic acid in CSF and the heterozygous
      SLC6A4 gene Gly56Ala plus 5-HTTLPR L/L promoter variants.
AB  - The known Gly56Ala mutation in the serotonin transporter SERT (or 5-HTT), encoded
      by the SLC6A4 gene, causes increased serotonin reuptake and has been associated
      with autism and rigid-compulsive behavior. We report a patient with macrocephaly
      from birth, followed by hypotonia, developmental delay, ataxia and a diagnosis of
      atypical autism (PDD-NOS) in retrospect at the age of 41/2years. Low levels of
      the serotonin end-metabolite 5-hydroxyindolacetic acid (5HIAA) in CSF were
      detected, and SLC6A4 gene analysis revealed the heterozygous Gly56Ala alteration
      and the homozygous 5-HTTLPR L/L promoter variant. These changes are reported to
      be responsible for elevated SERT activity and expression, suggesting that these
      alterations were responsible in our patient for low serotonin turnover in the
      central nervous system (CNS). Daily treatment with 5-hydroxytryptophan (and
      carbidopa) led to clinical improvement and normalization of 5HIAA, implying that
      brain serotonin turnover normalized. We speculate that the mutated 56Ala SERT
      transporter with elevated expression and basal activity for serotonin re-uptake
      is accompanied with serotonin accumulation within pre-synaptic axons and their
      vesicles in the CNS, resulting in a steady-state of lowered serotonin turnover
      and degradation by monoamine-oxidase (MAO) enzymes in pre-synaptic or neighboring
      cells.

PMID- 21183372
TI  - Indications for the use of next-generation antiretroviral drugs in current
      clinical practice.
AB  - OBJECTIVE: To describe the indications for use, in medical practice, of next
      generation antiretroviral drugs (NGA): darunavir, raltegravir, maraviroc and
      etravirine. METHOD: An observational, transversal and descriptive study conducted
      in adult patients who have started to receive a NGA between May 2008 and April
      2009. The variables associated with the use of NGA were defined as follows: a)
      Variables related to efficacy: resistance confirmed by geno/phenotype tests or
      potencial resistance as a result of extensive exposure to antiretroviral agents,
      and/or severe immunological deterioration (CD4 less than 200 cells/mcl). b)
      Variables related to safety: prior toxicity to classic antiretroviral drugs
      and/or comorbidity which compromises their use. c) Combined efficacy and safety
      variable (main variable): prioritizing the variables which were detected, the
      patients were classified into three groups: multiresistant geno/phenotype (multi
      G/P), multiresistant as a result of treatment history and other situations. Data
      was obtained from electronic medical records, laboratory tests, and records of
      interviews and drugs dispensed by the Pharmacy Service. RESULTS: Seventy three
      patients, 40% of whom had an undetectable viral load and 38.4% who showed severe
      immunological deterioration, were included in the study. Multi-G/P occurred in
      45% and multiresistance as a result of treatment history was found in 33% of
      patients. Patients classified as belonging to the "other situations" category
      were characterized by having a greater viral load and a poorer immunological
      status. In 90% of the patients without multi-G/P two or more variables associated
      with the use of NGA were detected. DISCUSSION: The medical reality of using NGA
      shows that they play a role in clinical situations which are very different,
      specific and difficult to manage.

PMID- 21183375
TI  - Hip fracture in elderly patients: is mortality a fatality? Comment on the article
      entitled: "Epidemiology of osteoporosis-related fractures in France: a literature
      review".

PMID- 21183373
TI  - Comparison of daily, weekly or monthly pain assessments in hip and knee
      osteoarthritis. A 29-day prospective study.
AB  - OBJECTIVE: To compare the accuracy of daily and recalled pain measurements in hip
      and knee osteoarthritis (OA). METHODS: A prospective study investigating pain
      intensity over 29 days in patients with painful OA. Pain was assessed on days 1
      and 29 during visits. Between these two visits, daily (worst, least, usual, mean,
      at rest and during daily life) and recalled pain intensities were randomly
      recorded by telephone interview with a numerical rating scale. RESULTS: We
      studied 129 patients, with a mean age of 67.7 +/- 10.0 years, 27.1% males. Daily
      prospective assessments demonstrated that the strongest correlations were between
      'mean daily' and 'usual' pain (r=0.88) and between 'mean daily' and 'worst' pain
      (r=0.86). Retrospective assessments demonstrated a strong correlation between
      recalled pain intensities and calculated mean of daily assessments over the seven
      and 28 days (0.78 and 0.67, respectively), but weakened by adjustment for pain
      intensity on the day of recalled pain assessment. Anxiety and depression scores
      did not affect pain recall for 7 and 28 days. CONCLUSIONS: In hip and knee OA,
      prospective daily pain assessment can be performed either by assessing 'usual
      pain' or 'worst pain' of the day. When recalled over one and four weeks, recall
      pain intensity is well correlated with calculated mean of prospective daily pain
      assessments during the same period, but correlations are weaker as the length of
      period increases. Either for 1 and 4 weeks, retrospective assessments are
      influenced by current pain intensity at the end of the period.

PMID- 21183376
TI  - Decrease of inpatient mortality for hip fracture in France.
AB  - OBJECTIVE: Hip fracture is the most devastating osteoporotic fracture, increasing
      the risk of mortality. Recent data suggest a decrease in incidence of this
      fracture. Few data are available on potential changes in mortality. We studied
      the change of inpatient mortality from 2002 to 2008 in France. METHODS: Data were
      extracted from the French Hospital National Database. The absolute number of
      inpatient mortality for hip fracture was described as well as the case fatal rate
      and mortality rate adjusted on age and gender. Risk factors of inpatient
      mortality were assessed by multiple regressions. RESULTS: Inpatient mortality
      stay decreased from 3057 to 2350 in patients aged 40 years and over and in both
      gender. Inpatient mortality stays were more important in women and increased with
      age, but the case fatal rate was higher in men than in women (5.4 vs. 2.8% in
      2008). During the study period, the mortality rate (per 1,000,000) varied from
      132 to 88 and from 82 to 64 in women and men, respectively. In the older
      patients, case fatality and mortality rates decreased significantly during the
      study period. From 2008 data, age more or equal to 85 years, male gender, stay in
      intensive care and existence of some chronic or acute disease, especially
      cardiovascular disease, hepatic disease, renal insufficiency, and infection were
      significant determinants of inpatient mortality. CONCLUSION: Inpatient mortality
      after hip fracture decreased in France between 2002 and 2008, although age, male
      gender and comorbidities were identified as determinants of inpatient mortality.

PMID- 21183377
TI  - Influence of the experience of the reader on reliability of joint space width
      measurement. A cross-sectional multiple reading study in hip osteoarthritis.
AB  - OBJECTIVES: The objectives were to evaluate improvement in reliability of joint
      space width (JSW) measurements, according to the previous experience of the
      readers in hip osteoarthritis (OA). METHODS: Fifty radiographs in hip OA patients
      from a randomized controlled trial (ECHODIAH) were read 12 times by two readers
      with different levels of experience in radiographic interpretation. Intra-reader
      reliability and inter-reader reliability were assessed through calculation of the
      smallest detectable difference (SDD) and the intra-class correlation coefficient
      (ICC). RESULTS: Intra-reader reliability: for the experienced reader, no
      significant change in SDD was observed with repeated JSW measurements. For the
      junior reader, the SDD decreased significantly from 0.90 mm to 0.65 mm (P=0.002).
      A plateau of SDD was reached after reading 200 to 300 radiographs, with a value
      close to the mean SDD of the experienced reader (0.67 mm). ICCs were high (>0.88)
      for both the senior and the junior readers. Inter-reader reliability: no
      improvement in inter-reader reliability was noted with repeated measurements of
      JSW (SDD=0.81 mm). However, no additional training sessions were performed. ICCs
      were high (>0.85). CONCLUSION: This study indicated for the first time a learning
      curve in analyzing JSW in hip OA for an inexperienced reader. After analyzing 200
      to 300 radiographs, the junior reader reached an intra-reader reliability similar
      to the experienced reader. Moreover, the information brought by the ICC was not
      sufficient, suggesting that the SDD should be systematically reported in studies
      evaluating OA radiographic progression, on top of the ICC, to help in
      interpreting the JSW reliability.

PMID- 21183378
TI  - Paradoxical reaction causing tuberculous arthritis and soft-tissue abscess in a
      non-HIV infected, lymphopenic, vitamin D deficient patient with disseminated
      tuberculosis. A coincidence or an immunological conundrum?

PMID- 21183379
TI  - Management of Raynaud's phenomenon and digital ulcers in systemic sclerosis.
AB  - Raynaud's phenomenon (RP) and digital ulcers (DU) are the clinical manifestations
      of vasculopathy in systemic sclerosis. Both interfere with hand function and hold
      the possibility of severe complications, thus adversely influencing patients'
      quality of life. Managing RP and DU is often a challenge for the treating
      physician, who has to establish a treatment plan based upon knowledge of the
      current therapeutic options. The first step is to differentiate primary from
      secondary RP, where combining history and physical examination with diagnostic
      modalities, such as nailfold capillaroscopy, aids in reaching the correct
      diagnosis. Next a wide range of treatment options is offered nowadays, starting
      from first-line agents, as calcium channel blockers, to the more targeted-ones,
      like endothelin receptor antagonists. Research and clinical experience with each
      agent are reviewed in the text, as well as the combinations that more recently
      gain field in the treatment of DU.

PMID- 21183381
TI  - Myositis ossificans circumscripta of the leg after an old gunshot injury.

PMID- 21183380
TI  - Interleukin-1beta activation during acute joint inflammation: a limited role for
      the NLRP3 inflammasome in vivo.

PMID- 21183382
TI  - [The myofibroblastic inflammatory tumours: A fortuitous association or an unknown
      postpartum complication].
AB  - The inflammatory myofibroblastic tumour has clinical, biological or histological
      features sometimes misleading with a septic condition. Presenting symptoms are
      variable and arising circumstances remain obscure. We report three cases
      occurring in a postpartum context. The first patient, a 28-year-old female, had
      left psoitis with a sepsis the first day postpartum in relation with an
      inflammatory myofibroblastic tumour of the meso-ovary. The second patient, a 40
      year-old woman, had a hepatic inflammatory myofibroblastic tumour revealed by a
      ruptured sub-capsular haematoma of the liver in the forth day postpartum. The
      third patient, a 32-year-old woman, had a pulmonary inflammatory myofibroblastic
      tumour, diagnosed 5 months after a delivery and which recurred 10 years after
      surgical treatment. These cases illustrate the difficulty to diagnose
      inflammatory myofibroblastic tumour, particularly in postpartum.

PMID- 21183383
TI  - [Spontaneous hepatic rupture during an uncomplicated twin pregnancy].
AB  - Liver subcapsular haematoma and its consequence, spontaneous hepatic rupture, are
      very rare complications of pregnancy. They are mainly associated with pre
      eclampsia. The diagnosis is difficult and the maternal and fetal mortality rates
      are high. We report the case of a spontaneous hepatic rupture on a normal liver
      during an uncomplicated twin pregnancy with a favorable outcome for both the
      mother and the newborns.

PMID- 21183384
TI  - [Endometriosis and fertility: Results after surgery and Assisted Reproductive
      Technology (ART)].
AB  - OBJECTIVE: To evaluate fertility outcomes after laparoscopic and ART management
      of endometriosis in an infertile population. PATIENTS AND METHODS: Retrospective
      analysis including 79 infertile patients treated by laparoscopic surgery.
      Fertility was studied in relation to pregnancy's mode (spontaneous or ART) and to
      endometriosis stages (rAFS). RESULTS: After laparoscopy, 8.9% of patients had a
      spontaneous pregnancy. IIU led to a cumulative rate of pregnant women of 21.5%.
      Then after laparoscopy, IIU and IVF, 68.4% of patients were pregnant. The average
      delay was 460 days between laparoscopy and spontaneous pregnancy, 271 days
      between surgery and IIU pregnancy and 600 days between surgery and IVF pregnancy.
      Among women with stages I-II endometriosis (62 cases), 11.3% patients obtained a
      spontaneous pregnancy, the cumulative rate of pregnant women after laparoscopy
      and IIU was 25,8%. After laparoscopy, IIU and IVF, 66.1% of patients were
      pregnant. The average post-surgical time to spontaneous pregnancy was 460 days.
      The average delay between surgery and IIU pregnancy was 279 days and 589 days
      between surgery and IVF pregnancy. In case of stages III-IV (17 patients), 76.4%
      of pregnancies were obtained. No spontaneous pregnancy was observed. 94.1% of
      patients were treated with IVF, leading to a global rate of pregnancy of 70.5%.
      The average delay between surgery and IVF pregnancy was 563 days. CONCLUSIONS:
      With a combination of surgery and ART, two-third of patients were pregnant with
      an average time between surgery and pregnancy of less than two years. This
      combination (surgery and ART) increases the chances of becoming pregnant. At the
      moment, the delay between surgery and ART needs to be established.

PMID- 21183385
TI  - [Ogilvie's syndrome after cesarean section: A case report].
AB  - Ogilvie's syndrome is a rare postsurgical complication. The high mortality rate
      (normally 15 to 31% and up to 45% after caecal perforation) explains the
      seriousness of this clinical situation. The early diagnosis is made by plain
      abdominal X-ray. Conservative treatment is usually effective and surgery should
      be reserved for complicated cases or refractory to conservative treatment. We
      report a case of Ogilvie's syndrome after cesarean section, which has been
      treated by conservative methods.

PMID- 21183386
TI  - [Perimenopausal discovery of endometriomas on ovarian abscess].
AB  - Ovarian abscess is a rare gynaecological diagnosis. The case reported is the one
      of an unexplained fever with a strong physical alteration during more than 14
      days occurring around the menopause, at the age of 54. It has been discovered an
      ovarian tumour which was, infact, an infected endometrioma. The patient never
      complained from endometriosis during her reproductive life. She had no other risk
      factor for ovarian abscess.

PMID- 21183387
TI  - [Complications of radical surgery for advanced ovarian cancer].
AB  - Treatment of advanced ovarian cancer should include surgery with optimal
      cytoreduction, which is the first prognosis factor. This surgery usually requires
      extensive resection (pelvic surgery, extensive lymphadenectomy, upper abdominal
      surgery and sometimes multiple intestinal resection). The complete surgery
      usually requires a resection of the diaphragm peritoneum in 10 to 100% of cases,
      intestinal resection in 20 to 100% of cases, splenectomy in 1 to 33% of cases,
      pancreatectomy in 0 11% of cases, resection of liver metastases in 0 to 16% of
      cases and cholecystectomy in 2 to 20% of cases. The main complications reported
      were digestive fistula (1.4 to 8.2%), lymphocyst (0.6 to 32%), septic
      complications (3.7 to 41.4%) and pulmonary complications (0 to 59%) in case of
      diaphragmatic surgery. The postoperative mortality ranges from 0.3 to 5.7%.
      Radical surgery increases the rate of complete cytoreduction with significant
      morbidity and postoperative mortality. Because these complications decrease
      survival, it is essential to assess the risk of occurrence of these events to
      inform patients.

PMID- 21183388
TI  - [Spontaneous evisceration of an abdominal pregnancy. Report of a case in
      Madagascar].
AB  - Authors report the case of a 29-year-old woman who presented a 34-weeks abdominal
      pregnancy. Spontaneous foetal evisceration was observed on abdominal caesarean
      operation scar performed previously by median infra-umbilical incision. Clinical
      features and treatment are discussed in developing country environment.

PMID- 21183389
TI  - [Placenta percreta: A rare etiology of spontaneous uterine perforation in the
      second trimester of pregnancy].
AB  - Placenta accreta is an abnormal adherence of placenta to the uterine wall without
      interposition of decidua basalis. Placenta percreta is the rarest form but may
      complicate the pregnancy with acute severe hemorrhage. We report a case of
      placenta percreta with multiple perforations of an unscarred uterus reaveled by
      hemoperitoneum at 22 weeks in a 33-years-old gravida 2 para 1. Emergency total
      hysterectomy was performed. Risk factors, clinical approach and therapeutic
      managements are discussed.

PMID- 21183390
TI  - [Voluminous juvenile papillomatosis: Diagnostic, therapeutic and prognostic
      difficulties - a case report].
AB  - The juvenile papillomatosis is a rare entity. We shall systematically check for a
      cancer. A 20-year-old woman patient without any familial medical history of
      breast carcinoma, was presenting a voluminous nodule of the left breast. A core
      needle biopsy allowed to diagnose papilloma. A conservative surgical treatment
      was proposed and realized despite any possibility of complete resection.
      Histological examination of the surgical specimen concluded to a juvenile
      papillomatosis. A closed follow-up was proposed to the patient. This case
      illustrates the difficulty of a voluminous tumor surgery on a young woman. The
      main problem is to combine the cosmetic constraints with oncology risk.

PMID- 21183391
TI  - [Malignant degeneration of benign cystic teratoma of the ovary].
AB  - Malignant transformation of mature cystic teratoma of the ovary is a rare
      complication occurring preferentially during peri- and post-menopausal period. No
      clinical nor radiological, nor biological signs are specific to malignant
      transformation. The treatment is surgical and similar to that of epithelial
      tumors of the ovary. We report an observation of a squamous cell carcinoma
      developed on a mature cystic teratoma of the ovary, in a patient aged 46 years.

PMID- 21183392
TI  - Robust identification and localization of intramedullary nail holes for distal
      locking using CBCT: a simulation study.
AB  - Closed intramedullary nailing is a common technique for treatment of femur and
      tibia fractures. The most challenging step in this procedure is the precise
      placement of the lateral screws that stabilize the fragmented bone. The present
      work concerns the development and the evaluation of a method to accurately
      identify in the 3D space the axes of the nail hole canals. A limited number of
      projection images are acquired around the leg with the help of a C-arm. On two of
      them, the locking hole entries are interactively selected and a rough
      localization of the hole axes is performed. Perpendicularly to one of them, cone
      beam computed tomography (CBCT) reconstructions are produced. The accurate
      identification and localization of the hole axes are done by an identification of
      the centers of the nail holes on the tomograms and a further 3D linear regression
      through principal component analysis (PCA). Various feature-based approaches
      (RANSAC, least-square fitting, Hough transform) have been compared for best
      matching the contours and the centers of the holes on the tomograms. The
      robustness of the suggested method was investigated using simulations.
      Programming is done in Matlab and C++. Results obtained on synthetic data confirm
      very good localization accuracy - mean translational error of 0.14 mm (std=0.08
      mm) and mean angular error of 0.84 degrees  (std=0.35 degrees ) at no radiation
      excess. Successful localization can be further used to guide a surgeon or a robot
      for correct drilling the bone along the nail openings.

PMID- 21183393
TI  - Sonographic abnormalities in idiopathic restless legs syndrome (RLS) and RLS in
      Parkinson's disease.
AB  - We aimed to investigate and compare sonographic abnormalities in the substantia
      nigra (SN) in patients with idiopathic restless legs syndrome (iRLS), those with
      RLS and Parkinson's disease (RLS-PD), those with idiopathic Parkinson's disease
      (iPD), and healthy controls. Study participants totaled 60 patients with RLS (41
      iRLS, 19 RLS-PD), 25 iPD patients, and 35 age-matched healthy controls. Comparing
      all groups, the SN region's echogenicity area in the iRLS patients was
      significantly decreased compared with that in the PD-RLS, iPD, and control groups
      (p < 0.0001), and the PD-RLS group demonstrated a significantly increased
      echogenicity area compared with the control group (p < 0.05) and iRLS group (p <
      0.0001). We found that the RLS-PD group's sonological results and clinical
      findings were different from those of the iRLS group.

PMID- 21183394
TI  - Novel insights into plant light-harvesting complex II phosphorylation and 'state
      transitions'.
AB  - Plants need a highly responsive regulatory system to keep photosynthetic light
      reactions in balance with the needs and restrictions of the downstream
      metabolism. This mechanism optimises plant growth under naturally fluctuating
      light conditions. In this opinion article, we present a model addressing the
      biological role of the light intensity-controlled phosphorylation of light
      harvesting complex II (LHCII) proteins and its relation with the non
      photochemical quenching of excitation energy (NPQ). We overturn a long held view
      of the possible role of 'state transitions'. Instead, we discuss the interplay
      between LHCII protein phosphorylation and NPQ, a mechanism that is crucial for
      regulating excitation energy distribution to the two photosystems (PSII and PSI)
      and balancing the intersystem electron flow despite constant fluctuations in
      light intensity.

PMID- 21183395
TI  - An integrated diagnosis and therapeutic system using intra-operative 5
      aminolevulinic-acid-induced fluorescence guided robotic laser ablation for
      precision neurosurgery.
AB  - We have developed an integrated diagnosis and therapeutic system for precision
      malignant gliomas resection during neurosurgery. A combination of three
      dimensional (3-D) magnetic resonance imaging (MRI) navigation and 5
      aminolevulinic acid (5-ALA)-induced fluorescence based intra-operative tumor
      diagnosis technique has been incorporated into a robotic laser ablation
      neurosurgery system with an automatic focusing and robotic scanning mechanism. 5
      ALA is a non-fluorescent prodrug that leads to intracellular accumulation of
      fluorescent protoporphyrins IX (PpIX) in malignant glioma. The PpIX tends to
      accumulate in pathological lesions, and emits red fluorescence when excited by
      blue light. This fluorescence is illuminated with laser excitation, enables intra
      operative identification of the position of a tumor and provides guidance for
      resection with laser photocoagulation. The information provided by the MRI is
      enhanced by the intra-operative 5-ALA fluorescence data, and this enhanced
      information is integrated into a robotic laser ablation system. The accuracy of
      the fluorescent measurement of the tumor is improved using high-precision
      spectral analysis. The fluorescence assists in the detection of malignant brain
      tumors intra-operatively and improves their removal rate.

PMID- 21183396
TI  - Antiviral drug resistance and helicase-primase inhibitors of herpes simplex
      virus.
AB  - A new class of chemical inhibitors has been discovered that interferes with the
      process of herpesvirus DNA replication. To date, the majority of useful
      herpesvirus antivirals are nucleoside analogues that block herpesvirus DNA
      replication by targeting the DNA polymerase. The new helicase-primase inhibitors
      (HPI) target a different enzyme complex that is also essential for herpesvirus
      DNA replication. This review will place the HPI in the context of previous work
      on the nucleoside analogues. Several promising highly potent HPI will be
      described with a particular focus on the identification of drug-resistance
      mutations. Several HPI have good pharmacological profiles and are now at the
      outset of phase II clinical trials. Provided there are no safety issues to stop
      their progress, this new class of compound will be a major advance in the
      herpesvirus antiviral field. Furthermore, HPI are likely to have a major impact
      on the therapy and prevention of herpes simplex virus and varicella zoster in
      both immunocompetent and immunocompromised patients alone or in combination with
      current nucleoside analogues. The possibility of acquired drug-resistance to HPI
      will then become an issue of great practical importance.

PMID- 21183397
TI  - Oral cavity and oropharynx squamous cell carcinoma with metastasis to the parotid
      lymph nodes.
AB  - To increase awareness of the potential of oral and oropharyngeal squamous cell
      carcinoma (SCC) to metastasize to the parotid region. We retrospectively reviewed
      patients who had undergone parotidectomy for metastatic oral or oropharyngeal SCC
      at a single tertiary care facility from January 1988 to January 2004. Exclusion
      criteria were a history of cutaneous SCC of head and neck or extension of primary
      tumor into the parotid gland. Twelve patients met study criteria. Parotid
      metastasis represented the initial disease manifestation in 4 cases. In 1 case,
      parotid metastasis presented synchronously with the primary tumor. Parotid
      metastasis represented recurrent disease in the other 7 cases. Primary subsites
      included tongue base (n=4), tonsil (n=3), lateral pharyngeal wall (n=2), oral
      floor (n=1), maxillary alveolus (n=1), and retromolar trigone (n=1). Pathologic
      findings showed grade 3 or 4 SCC in all patients. Parotid metastasis was located
      in the inferior parotid nodes in 7 cases; multiple superficial nodes, 3 cases;
      and both deep and superficial nodes, 2 cases. Oral and oropharyngeal SCC can
      metastasize to the intraparotid lymph nodes. The inferior parotid nodes are most
      commonly involved, and patients generally have substantial associated cervical
      metastases. When treating patients who have oral or oropharyngeal cancer with
      substantial cervical metastasis, physicians should consider removing the inferior
      parotid lymph nodes. We recommend that when intraparotid lymph node metastasis is
      detected, total parotidectomy and multidisciplinary adjuvant therapy should be
      conducted.

PMID- 21183398
TI  - The roles of hope and optimism on posttraumatic growth in oral cavity cancer
      patients.
AB  - To investigate the association of the positive coping strategies, hope and
      optimism, on posttraumatic growth (PTG) in oral cavity (OC) cancer patients. A
      retrospective cross-sectional study was conducted and performed in the outpatient
      station of the Oral and Maxillofacial Surgery at the University of Hong Kong,
      Hong Kong SAR, PR China. Fifty patients successfully treated for OC cancer were
      recruited after their informed consents had been obtained during the review
      clinic. During their regular follow-up controls in the outpatient clinic, the
      patients compiled the posttraumatic growth inventory (PTGI) questionnaire, hope
      scale (HS) and the life orientation scale-revised (LOT-R). Hope and optimism
      correlated significantly positive with PTG and accounting together for a 25%
      variance of posttraumatic growth. Hope positively correlated with posttraumatic
      growth (r=.49, p<.001) as well as optimism (r=.31, p<.05). When compared to
      unmarried patients, married patients showed high levels of PTG and hope (married
      participants: mean=53.15, SD=11.04; unmarried participants: mean=41.00, SD=6.36;
      t (48)=2.403, p<.05). Hope and optimism represent important indicators for PTG in
      OC cancer patients. An intact dyad relationship seems to be important for hope
      and consecutive higher levels of PTG when compared to unmarried patients.
      Supportive psychological treatment strategies related to these two coping factors
      might be beneficial for OC cancer patients.

PMID- 21183399
TI  - Nucleic acids determination using the complex of eriochrome black T and silver
      nanoparticles in a resonance light scattering technique.
AB  - A novel method for the determination of nucleic acids by using silver
      nanoparticle (AgNPs)-eriochrome black T (EBT) as a resonance light scattering
      (RLS) probe has been developed. Under optimum conditions, there are linear
      relationships between the quenching extent of RLS intensity and the concentration
      of nucleic acids in the range of 4.0*10(-9)-4.0*10(-7), 4.0*10(-7)-1.6*10(-6) g
      mL(-1) for fish sperm DNA (fsDNA) and 4.0*10(-8)-2.0*10(-6) g mL(-1) for yeast
      RNA (yRNA). Their detection limits (S/N=3) are 2.0 ng mL(-1) and 21 ng mL(-1),
      respectively. The results indicate that AgNPs can form wirelike aggregates and
      nanoslices in the presence of the EBT. Whereas, when nucleic acids are added into
      the AgNPs-EBT system, the dynamic balance of AgNPs-EBT system is destroyed and
      the nanoparticles undergo dispersion again, leading to the RLS intensity of AgNPs
      EBT system quenching. Meanwhile, the conformation of fsDNA is changed by the
      synergistic effect of AgNPs and EBT.

PMID- 21183400
TI  - Molecular structure and vibrational analysis of 3-Ethylpyridine using ab initio
      HF and density functional theory (B3LYP) calculations.
AB  - The FT-Raman and FT-IR spectra for 3-Ethylpyridine (3-EP) have been recorded in
      the region 4000-100 cm(-1) and compared with the harmonic vibrational frequencies
      calculated using HF/DFT (B3LYP) method by employing 6-31G(d,p) and 6-311++G(d,p)
      basis set with appropriate scale factors. IR intensities and Raman activities are
      also calculated by HF and DFT (B3LYP) methods. Optimized geometries of the
      molecule have been interpreted and compared with the reported experimental values
      of some substituted benzene. The experimental geometrical parameters show
      satisfactory agreement with the theoretical prediction from HF and DFT. The
      scaled vibrational frequencies at B3LYP/6-311++G(d,p) seem to coincide with the
      experimentally observed values with acceptable deviations. The theoretical
      spectrograms (IR and Raman) have been constructed and compared with the
      experimental FT-IR and FT-Raman spectra. Some of the vibrational frequencies of
      the pyridine are effected upon profusely with the C2H5 substitutions in
      comparison to pyridine and these differences are interpreted.

PMID- 21183401
TI  - Study on the interactions between ginsenosides and lysozyme under acidic
      condition by ESI-MS and molecular docking.
AB  - In order to study the different effects of ginsenosides with similar structures,
      research on interactions between ginsenoside Rg1, Re and lysozyme was carried out
      by electrospray ionization mass spectrometry (ESI-MS) and molecular docking. The
      1:1 and 2:1 noncovalent complexes of ginsenosides and lysozyme were observed in
      the mass spectra and the dissociation constants for them were directly calculated
      based on peak intensities of lysozyme and its noncovalent complexes with
      ginsenosides. The results showed that the 1:1 complex of ginsenoside Rg1 and
      lysozyme was more stable than that of ginsenoside Re and lysozyme. As the acidity
      increased, the stabilities of the 1:1 complexes of Rg1, Re and lysozyme both
      decreased. Interestingly, as the acidity increased, the stability of the 2:1
      complex of Rg1 and lysozyme increased while that of Re decreased. From the result
      of molecular docking, ginsenosides interacted with the active sites of lysozyme.
      And the stability of the complexes could be affected by the conformation changes
      of lysozyme as acidity increased.

PMID- 21183402
TI  - Online detection of potential duplicate medications and changes of physician
      behavior for outpatients visiting multiple hospitals using national health
      insurance smart cards in Taiwan.
AB  - OBJECTIVES: Doctor shopping (or hospital shopping), which means changing doctors
      (or hospitals) without professional referral for the same or similar illness
      conditions, is common in Hong Kong, Taiwan and Japan. Due to the lack of
      infrastructure for sharing health information and medication history among
      hospitals, doctor-shopping patients are more likely to receive duplicate
      medications and suffer adverse drug reactions. The Bureau of National Health
      Insurance (BNHI) adopted smart cards (or NHI-IC cards) as health cards in Taiwan.
      With their NHI-IC cards, patients can freely access different medical
      institutions. Because an NHI-IC card carries information about a patient's
      prescribed medications received from different hospitals nationwide, we used this
      system to address the problem of duplicate medications for outpatients visiting
      multiple hospitals. METHODS: A computerized physician order entry (CPOE) system
      was enhanced with the capability of accessing NHI-IC cards and providing alerts
      to physicians when the system detects potential duplicate medications at the time
      of prescribing. Physician responses to the alerts were also collected to analyze
      changes in physicians' behavior. Chi-square tests and two-sided z-tests with
      Bonferroni adjustments for multiple comparisons were used to assess statistical
      significance of differences in actions taken by physicians over the three months.
      RESULTS: The enhanced CPOE system for outpatient services was implemented and
      installed at the Pediatric and Urology Departments of Taipei Medical University
      Wan-Fang Hospital in March 2007. The "Change Log" that recorded physician
      behavior was activated during a 3-month study period from April to June 2007. In
      67.93% of patient visits, the physicians read patient NHI-IC cards, and in 16.76%
      of the reads, the NHI-IC card contained at least one prescribed medication that
      was taken by the patient. Among the prescriptions issued by physicians, on
      average, there were 2.36% prescriptions containing at least one medication that
      might be duplicative to the prior prescriptions stored in NHI-IC cards. The rate
      of potential duplicate medication alerts for the Pediatric Department was higher
      than that for the Urology Department (2.78% versus 1.67%). However, the rate of
      revisions to prescriptions was higher in the Urology Department than the
      Pediatric Department. Overall, the rate of physicians reviewing and revising
      their prescriptions was 29.25%; the rate of physicians reviewing without revising
      their prescriptions was 43.62%; the rate of physicians turning off the alert
      screens right after the screens popped up (overridden) was 27.13%. Thus,
      physicians accepted alerts to review their prescriptions with patients in most
      situations (72.87%). Moreover, over the study period, the rate of total revisions
      made to prescriptions increased and the "overridden" rate decreased. CONCLUSIONS:
      Our approach enhances the capability of CPOE systems using NHI-IC cards as a
      nationwide infrastructure to provide more complete patient health information and
      medication history sharing among hospitals in Taiwan. Thus, our system can
      provide a better prescribing tool to help physicians detect potential duplicate
      medications for frequent doctor-shopping patients and hence enhance patient
      safety across hospital boundaries. However, the effectiveness of detecting
      duplicate medications with our approach is very much dependent on the
      completeness of NHI-IC cards, which in turn primarily depends on physician use of
      the cards when prescribing.

PMID- 21183403
TI  - The variance modulation associated with the vestibular evoked myogenic potential.
AB  - OBJECTIVE: Model considerations suggest that the sound-induced inhibition
      underlying the vestibular evoked myogenic potential (VEMP) briefly reduces the
      variance of the electromyogram (EMG) from which the VEMP is derived. Although
      more difficult to investigate, this inhibitory modulation of the variance
      promises to be a specific measure of the inhibition, in that respect being
      superior to the VEMP itself. This study aimed to verify the theoretical
      predictions. METHODS: Archived data from 672 clinical VEMP investigations,
      comprising about 300,000 EMG records altogether, were pooled. Both the complete
      data pool and subsets of data representing VEMPs of varying degrees of
      distinctness were analyzed. The data were generally normalized so that the EMG
      had variance one. RESULTS: Regarding VEMP deflection p13, the data confirm the
      theoretical predictions. At the latency of deflection n23, however, an additional
      excitatory component, showing a maximal effect around 30 ms, appears to
      contribute. CONCLUSIONS: Studying the variance modulation may help to identify
      and characterize different components of the VEMP. In particular, it appears to
      be possible to distinguish between inhibition and excitation. SIGNIFICANCE: The
      variance modulation provides information not being available in the VEMP itself.
      Thus, studying this measure may significantly contribute to our understanding of
      the VEMP phenomenon.

PMID- 21183404
TI  - Toward a gaze-independent matrix speller brain-computer interface.

PMID- 21183405
TI  - Genomics of biotrophic, plant-infecting plasmodiophorids using in vitro dual
      cultures.
AB  - The plasmodiophorids are a phylogenetically distinct group of parasitic protists
      that infect plants and stramenopiles, causing several important agricultural
      diseases. Because of the obligate intracellular part of their lifecycle, none of
      the plasmodiophorids has been axenically cultured. Further, the molecular biology
      of the plasmodiophorids is poorly understood because pure cultures are not
      available from any species. We report on an in-vitro dual culture system of the
      plasmodiophorids Plasmodiophora brassicae and Spongospora subterranea with their
      respective plant hosts, Brassica rapa and Solanum tuberosum. We show that these
      plasmodiophorids are capable of initiating and maintaining stable, long-term
      plant cell callus cultures in the absence of exogenous plant growth regulators.
      We show that callus cultures harbouring S. subterranea provide an excellent
      starting material for gene discovery from this organism by constructing a pilot
      scale DNA library. Bioinformatic analysis of the sequences established that
      almost all of the DNA clones from this library were from S. subterranea rather
      than the plant host. The Spongospora genome was found to be rich in
      retrotransposable elements, and Spongospora protein-coding genes were shown to
      contain introns. The sequence of a near full-length non-LTR retrotransposon was
      obtained, the first transposable element reported from a cercozoan protist.

PMID- 21183407
TI  - Student nurses' learning processes in interaction with psychiatric patients: a
      qualitative investigation.
AB  - When the Danish government converted the national practice-oriented nursing
      qualification from a vocational course to a bachelor's degree in 2002, the
      clinical training component was scaled back. Accordingly, mentors needed to
      optimise students' learning from this curtailed clinical practice. A fuller
      understanding of how student nurses function and learn during clinical training
      is vital. This article presents the findings of a qualitative investigation of
      student nurses' learning processes during their clinical placement in psychiatric
      nursing practice. An explorative and qualitative descriptive approach was chosen.
      The theoretical framework includes Jarvis' concept of 'disjuncture', because it
      offers a theoretical way of understanding the empirical phenomenon of 'non
      routine-situations'. Heller's concept of 'everyday life activities' is also drawn
      on, for its contribution to understanding and analysing the content of student
      nurses' learning processes. Data was generated from qualitative, semi-structured
      interviews with, observations of, and obser-views with, eleven students. The
      obser-view process is my development. It is a common reflection between
      researcher and research participant which takes place just after the researcher's
      observation of the participant in interaction with a patient. The role of the
      researcher is to be a catalyst for the reflection. Using qualitative content
      analysis, a model of student nurses learning processes, termed the 'Windmill of
      Learning Processes' was developed as a result. A key finding is that students and
      mentors are typically unaware of potential learning situations. Crucially, once
      students are made aware of this fact, their clinical learning can be enhanced. In
      this regard, the Windmill of Learning Processes is offered as a pedagogical tool
      for students and mentors.

PMID- 21183408
TI  - Ileal bladder augmentation and vitamin B12: levels decrease with time after
      surgery.
AB  - OBJECTIVE: We investigated vitamin B12 deficiency following ileocystoplasty in
      children. METHODS: Patients who underwent ileocystoplasty between December 1993
      and September 2006 were included and B12 levels were retrospectively analysed.
      Patients with a serum B12 of less than 150 pg/ml were considered deficient. The
      distance of the ileal segment from the ileocaecal valve was recorded. RESULTS:
      There were 105 patients in the series; 61 were male. Mean age at surgery was 7.7
      years (SD = 3.9). The mean interval from surgery to most recent B12 level was 50
      months (SD = 30). None of the patients were on B12 supplementation. Two patients
      were B12 deficient, both more than 7 years after surgery; 44% of patients with
      levels available 7 years after surgery had a B12 below 300 pg/ml. There was a
      significant negative correlation between B12 level and length of follow up
      (Spearman's rank, P < 0.01). Twenty patients with an ileal segment sparing 60 cm
      from the ileocaecal valve had a higher mean B12 (524 vs 419, SEM 60 vs 28). This
      was not statistically significant. CONCLUSION: We demonstrate a reduction in
      serum B12 level with time following ileocystoplasty. These patients should have
      their B12 levels measured in the long term.

PMID- 21183409
TI  - Effects of emotional excitement on heart rate and blood pressure dynamics in
      patients with coronary artery disease.
AB  - The incidence of adverse cardiovascular events is higher among spectators of
      exciting sports events, but the mechanistic link between the events is not known.
      We assessed the heart rate (HR) and blood pressure (BP) dynamics of enthusiastic
      male ice hockey spectators (60 +/- 9 years) with coronary artery disease (CAD)
      during Finnish national league ice hockey play-off final matches. Twenty-four
      hour ambulatory ECG (n = 55) and BP (n = 17) were recorded at the time of the
      match and on a control day. Beat-to-beat R-R intervals and BP were recorded
      during the match and a bicycle exercise at equal HR levels (n = 21). Systolic and
      diastolic BP were significantly higher 1h before, during, and 1h after the match
      than on the control day, e.g., the highest systolic BP was 180 +/- 14 vs. 145 +/-
      15 and diastolic 103 +/- 13 vs. 82 +/- 11 mmHg (p<0.001 for both). HR was higher
      throughout the match (p<0.05) and remained elevated 2h after the match (p<0001),
      and measures of HR variability were decreased during the match (p<0.01). Low
      frequency variability in BP was higher during the match than during the exercise
      test (p<0.01). The results show that cardiac vagal outflow is attenuated and
      vasomotor sympathetic activity elevated during exciting sports events and BP
      dynamics differ from those occurring during physical exercise at equal HRs. The
      autonomic reactions may partly explain the vulnerability to cardiovascular events
      caused by this type of leisure-time emotional excitement.

PMID- 21183411
TI  - Target-guided isolation and purification of antioxidants from Selaginella
      sinensis by offline coupling of DPPH-HPLC and HSCCC experiments.
AB  - Selaginella sinensis (Selaginellaceae) is used extensively in traditional Chinese
      medicine (TCM) for the treatment of many kinds of chronic diseases. In this
      study, fractionation of the methanol extract of S. sinensis by different polarity
      solvents indicated the ethyl acetate fraction exhibited an potent 1,1-diphenyl-2
      picryhydrazyl (DPPH) radical scavenging activity with the IC(50) value of 44.9
      MUM. In order to evaluate the scientific basis, antioxidant peaks were firstly
      screened using DPPH spiking test through high performance liquid chromatography
      (DPPH-HPLC). Under the target-guidance of DPPH-HPLC experiment, two flavonoids
      and six biflavonoids, quercetin (1), apigenin (2), amentoflavone (3),
      robustaflavone (4), 2,3-dihydroamentaflavone (5), hinokiflavone (6), 4'-O-methyl
      robustaflavone (7) and ginkgetin (8) were separated by high-speed counter-current
      chromatography (HSCCC) method using n-hexane-ethyl acetate-methanol-water
      (8:8:9:7) as the solvent system with purities 98.2%, 97.6%, 99.4%, 92.3%, 98.5%,
      98.9% and 99.6%, respectively. The structures were identified by electrospray
      ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR)
      analysis. Antioxidant activity of eight isolated compounds was assessed by the
      radical scavenging effect on DPPH radical, compound 1 showed strongest
      antioxidant activities with IC(50) values of 3.2 MUM, while compounds 2-8 showed
      weak antioxidant activities. This is the first report on simultaneous separation
      of eight antioxidant compounds from S. sinensis by HSCCC, moreover, apigenin and
      4'-O-methyl-robustaflavone were first identified from this plant. Results of the
      present study indicated that the combinative method using DPPH-HPLC and HSCCC
      could be widely applied for rapid screening and isolating of antioxidants from
      complex TCM extract.

PMID- 21183410
TI  - Schizosaccharomyces pombe Mms1 channels repair of perturbed replication into
      Rhp51 independent homologous recombination.
AB  - In both Schizosaccharomyces pombe and Saccharomyces cerevisiae, Mms22 and Mms1
      form a complex with important functions in the response to DNA damage, loss of
      which leads to perturbations during replication. Furthermore, in S. cerevisiae,
      Mms1 has been suggested to function in concert with a Cullin-like protein,
      Rtt101/Cul8, a potential paralog of Cullin 4. We performed epistasis analysis
      between Deltamms1 and mutants of pathways with known functions in genome
      integrity, and measured the recruitment of homologous recombination proteins to
      blocked replication forks and recombination frequencies. We show that, in S.
      pombe, the functions of Mms1 and the conserved components of the Cullin 4
      ubiquitin ligase, Pcu4 and Ddb1, do not significantly overlap. Furthermore,
      unlike in S. cerevisiae, the function of the H3K56 acetylase Rtt109 is not
      essential for Mms1 function. We provide evidence that Mms1 function is
      particularly important when a single strand break is converted into a double
      strand break during replication. Genetic data connect Mms1 to a Mus81 and
      Rad22(Rad52) dependent, but Rhp51 independent, branch of homologous
      recombination. This is supported by results demonstrating that Mms1 is recruited
      to a site-specific replication fork barrier and that, in a Deltamms1 strain,
      Rad22(Rad52) and RPA recruitment to blocked forks are reduced, whereas Rhp51
      recruitment is unaffected. In addition, Mms1 appears to specifically promote
      chromosomal rearrangements in a recombination assay. These observations suggest
      that Mms1 acts to channel repair of perturbed replication into a particular sub
      pathway of homologous recombination.

PMID- 21183406
TI  - Therapeutic potential of beta-arrestin- and G protein-biased agonists.
AB  - Members of the seven-transmembrane receptor (7TMR), or G protein-coupled receptor
      (GPCR), superfamily represent some of the most successful targets of modern drug
      therapy, with proven efficacy in the treatment of a broad range of human
      conditions and disease processes. It is now appreciated that beta-arrestins, once
      viewed simply as negative regulators of traditional 7TMR-stimulated G protein
      signaling, act as multifunctional adapter proteins that regulate 7TMR
      desensitization and trafficking and promote distinct intracellular signals in
      their own right. Moreover, several 7TMR biased agonists, which selectively
      activate these divergent signaling pathways, have been identified. Here we
      highlight the diversity of G protein- and beta-arrestin-mediated functions and
      the therapeutic potential of selective targeting of these in disease states.

PMID- 21183412
TI  - Analysis of risperidone and 9-hydroxyrisperidone in human plasma, urine and
      saliva by MEPS-LC-UV.
AB  - Risperidone is currently one of the most frequently prescribed atypical
      antipsychotic drugs; its main active metabolite 9-hydroxyrisperidone contributes
      significantly to the therapeutic effects observed. An original analytical method
      is presented for the simultaneous analysis of risperidone and the metabolite in
      plasma, urine and saliva by high-performance liquid chromatography coupled to an
      original sample pre-treatment procedure based on micro-extraction by packed
      sorbent (MEPS). The assays were carried out using a C8 reversed-phase column and
      a mobile phase composed of 73% (v/v) acidic phosphate buffer (30 mM, pH 3.0)
      containing 0.23% triethylamine and 27% (v/v) acetonitrile. The UV detector was
      set at 238 nm and diphenhydramine was used as the internal standard. The sample
      pre-treatment by MEPS was carried out on a C8 sorbent. The extraction yields
      values were higher than 92% for risperidone and 90% for 9-hydroxyrisperidone,
      with RSD for precision always lower than 7.9% for both analytes. Limit of
      quantification values in the different matrices were 4 ng/mL or lower for
      risperidone and 6 ng/mL or lower for the metabolite. The method was successfully
      applied to plasma, urine and saliva samples from psychotic patients undergoing
      therapy with risperidone, with satisfactory accuracy results (recovery>89%) and
      no interference from other drugs. Thus, the method seems to be suitable for the
      therapeutic drug monitoring of schizophrenic patients using the three different
      biological matrices plasma, urine and saliva.

PMID- 21183413
TI  - [Positive 123I-MIBG in an infant with an abdominal mass].

PMID- 21183414
TI  - Rat trans-acting transactions and the genetics of complex traits.

PMID- 21183415
TI  - [Relationship between coronary collateral circulation and plasma levels of N
      terminal pro-B-type natriuretic peptide].
AB  - OBJECTIVE: There have been numerous investigations demonstrating protective
      effects of awell- grown coronary collateral circulation (CCC) on left ventricular
      systolic function. N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is
      released by ventricular myocardium as a result of increased myocardial wall
      stress. The aim of the study was to evaluate the relationship between CCC and
      plasma NT-pro-BNP levels. METHODS: Study group was retrospectively selected from
      patients who had a coronary angiography at our center between January 2008 and
      December 2009. One hundred and thirty patients having at least one totally
      occluded main coronary artery were included in this study. Collateral circulation
      was graded according to Rentrop score. Grade 0 and 1 are regarded as poor, and
      grade 2 and 3 - good CCC. Plasma NT-pro-BNP levels were measured by
      electrochemiluminescence immunoassay method and left ventricular ejection
      fraction (LVEF) were measured by modified Simpson method. We used Chi-square,
      Student t and Mann-Whitney-U tests for statistical analysis. RESULTS: Overall 57
      patients were found to have poor CCC and 73 patients have good CCC. Plasma NT-pro
      BNP levels (pg/ml)-median (minimum-maximum)- were 1319 (48-9753) in poor CCC
      group and 847 (16-5529) in good CCC group (p=0.004). LVEF was found to be -median
      (minimum-maximum)- 45% (30-55%) in poor CCC group and 50% (30-60%) in good CCC
      group (p=0.003). Correlation analysis demonstrated that collateral grade was
      negatively correlated with NT-pro-BNP levels (r=-0.252, p=0.004). CONCLUSION: We
      found that plasma NT-pro-BNP levels were more elevated in patients with poor CCC
      than in patients with good CCC. This finding may be explained with the protective
      effect of good CCC on LVEF.

PMID- 21183416
TI  - Diagnostic accuracy of P-wave dispersion in prediction of maintenance of sinus
      rhythm after external cardioversion of atrial fibrillation.
AB  - OBJECTIVE: P-wave dispersion (PWD) is an electrocardiographic measurement, which
      reflects a disparity in an atrial conduction. In this study, we aim to
      demonstrate the diagnostic accuracy of PWD in predicting recurrence of atrial
      fibrillation (AF) in patients with sinus rhythm restoration after external
      cardioversion. METHODS: This prospective, observational study consists of 26
      patients, who underwent external cardioversion for non-valvular persistent AF and
      successfully cardioverted to sinus rhythm (13 men, mean age 58.1 +/- 11 years).
      Twelve-lead surface electrocardiogram of each patient was recorded immediately
      after the external cardioversion process to measure the P-wave duration.
      Recurrent AF was assessed for each patient during the 12-month follow-up after
      restoring the sinus rhythm. Patients were divided into the 2 groups with respect
      to the AF recurrence (recurrent AF group, (n=19), and sinus rhythm group, (n=7))
      and variables that can affect AF development were compared between the two
      groups. Stepwise logistic regression analysis was used to identify the
      independent predictors of AF recurrence and ROC curve analysis was performed to
      determine the cut-off value of independent factors. RESULTS: The two groups have
      similar demographic, clinical and echocardiographic features. Patients with
      recurrent AF had significantly higher PWD than those who continued to have a
      sinus rhythm (80 +/- 21 msec vs 53 +/- 11 msec, p=0.001, respectively). There is
      a positive correlation observed between the increase in PWD and the risk of AF
      recurrence (r=0.643; p=0.001). In logistic regression analysis, PWD was found to
      be an independent predictor of AF recurrence (OR 1.192 (95% CI 1.032-1.375), p=
      0.013). Receiver operating characteristic analysis revealed that the best cut-off
      value of PWD for maintenance of sinus rhythm was 58 msec (sensitivity: 86%,
      specificity: 95%, AUC=0.917, 95% CI=0.785-1.05, p=0.001). CONCLUSION: This study
      suggests that PWD analysis after successful external cardioversion has diagnostic
      accuracy to predict the recurrence of AF.

PMID- 21183417
TI  - Effect of previous statin use on the incidence of sustained ventricular
      tachycardia and ventricular fibrillation in patients presenting with acute
      coronary syndrome.
AB  - OBJECTIVE: Recent studies suggest that statins have anti-arrhythmic effects. The
      aim of this study was to evaluate the effects of statins on sustained ventricular
      tachycardia or ventricular fibrillation (S-VT or VF) in patients presenting with
      acute coronary syndrome (ACS). METHODS: The population of this study consisted of
      consecutive patients admitted to coronary care unit. It was an observational case
      controlled retrospective analysis performed on prospective cohort. From a total
      of 1000 patients presenting with ACS, 241 were on and 759 were not on statin.
      Patient demographics, clinical characteristics and previous medical treatment
      including statins were recorded. A S-VT or VF episode during hospitalization was
      accepted as endpoint. Multiple logistic regression model was performed which
      considered the occurrence of S-VT or VF as the response variable. RESULTS:
      Sustained VT or VF occurred in 3.3% of patients in statin group and in 9% of
      patients in non-statin group. Univariate positive predictors of S-VT or VF were
      ST elevation myocardial infarction as clinical presentation, smoking and
      thrombolysis; univariate negative predictors of S-VT or VF were ejection
      fraction, use of acetylsalicylic acid before hospitalization, use of statin
      before hospitalization, initiation of clopidogrel at the hospital and normal
      coronary arteries. In the multiple logistic regression analysis, the only
      independent predictor of S-VT or VF was ejection fraction (OR 0.96; 95% CI 0.93
      to 0.99; p=0.005). CONCLUSION: Our results indicate that, although the incidence
      of S-VT/VF was significantly lower in patients with ACS and previous statin use;
      statin use is not an independent predictor of the occurrence of S-VT or VF in
      patients presenting with ACS.

PMID- 21183418
TI  - Influence of one-year treatment with lovastatin on myocardial remodeling and
      ischemia in patients with coronary artery disease.
AB  - OBJECTIVE: Emerging evidence assumes that statins have a benefit to influence the
      myocardial remodeling and ischemia in patients with coronary artery disease
      (CAD). Our aim was to investigate the possible and direct favorable effects of
      lovastatin on left ventricular (LV) systolic, diastolic function and myocardial
      ischemia in patients with CAD. METHODS: This randomized prospective study
      consisted of 83 patients (46 males; mean age 54.3 +/- 6.5 years) with CAD and
      dyslipidemia. All patients were randomized to following groups: the 1st group
      (n=44) received lovastatin (20-60 mg/day), hypolipidemic diet and physical
      training; the 2nd group (n=39) - hypolipidemic diet and physical training. Lipid
      spectrum, Doppler-echocardiography, bicycle exercise test and 24-hour ambulatory
      electrocardiographic monitoring were done at baseline and were repeated after 12
      months of treatment. The data were analyzed by using the paired and unpaired
      Student's t-tests. RESULTS: In the 1st group there was an improvement of lipid
      spectrum (p=0.05) without significant changes of liver transaminases and other
      side effects. After treatment LV ejection fraction increased from 59.8 +/- 8.04
      to 62.9 +/- 4.43% in lovastatin alone group (p=0.01). Unlike 2nd group, the 1st
      group's patients had also reduction of myocardial ischemia: increased exercise
      time (5.21 +/- 1.81 vs. 5.96 +/- 1.76 min; p=0.05), METS (4.42 +/- 0.6 vs. 4.78
      +/- 0.7; p=0.05), magnitude (1.12 +/- 0.34 vs. 0.81 +/- 0.19 mm; p=0.05) and
      duration (2.16 +/- 0.67 vs. 1.04 +/- 0.46 min, p=0.01) of ST segment depression ,
      as well as number of leads with ST segment depression (2.18 +/- 0.72 vs. 1.31 +/-
      0.67; p=0.05). CONCLUSION: Lipid-lowering therapy with lovastatin improved the LV
      systolic function and decreased myocardial ischemia.

PMID- 21183419
TI  - Protective effect of carnosine on adriamycin-induced oxidative heart damage in
      rats.
AB  - OBJECTIVE: Oxidative stress is one of the major factors involved in the
      pathogenesis of adriamycin (ADR)-induced cardiac dysfunction. The present study
      examined the antioxidant protective effects of carnosine (CAR) on adriamycin
      induced cardiac damage in rats. METHODS: Female Sprague Dawley rats were divided
      into four groups. Control (CONT, n=8, saline only i.v.); carnosine (CAR, n=8.10
      mg/kg/day, i.v.); adriamycin (ADR, n=10.4 mg/kg four times every 2 days for 8
      days, i.v.) alone and carnosine with adriamycin (CAR+ADR, n=10). Carnosine was
      given one week before adriamycin treatment and following one week with adriamycin
      treatment. After measurement of physiological functions, blood samples were
      collected for biochemical assays. The hearts were excised for hemodynamic study.
      Comparisons between different groups were made using ANOVA and posthoc Tukey
      test. RESULTS: Adriamycin produced evident cardiac damage revealed by;
      hemodynamic changes - decreased left ventricular developed pressure (p=0.01), the
      maximum-minimum rates of change in left ventricular pressure (+/- dP/dt, p=0.01),
      electrocardiogram (ECG) changes (elevated ST, decreased R-wave, p=0.001), cardiac
      injury marker changes (increased creatine kinase, lactate dehydrogenase,
      aspartate aminotransferase and alanine aminotransferase), plasma antioxidant
      enzymes activity changes (decreased superoxide dismutase, glutathione peroxidase,
      catalase activities, p=0.03) and lipid peroxidation (elevated malondialdehyde,
      p=0.05) to the control and carnosine groups. Carnosine treatment caused
      significant attenuation (p=0.05) of cardiac dysfunction induced by adriamycin
      (CAR+ADR), revealed by normalization of the ventricular function, ECG and
      biochemical variables. CONCLUSION: An increase in oxidative stress, superoxide
      dismutase, glutathione peroxidase levels, catalase inactivation and cardiac
      dysfunction induced by adriamycin were prevented by carnosine.

PMID- 21183420
TI  - Joseph Geza Sinkovics.

PMID- 21183421
TI  - Antileukemia and antitumor effects of the graft-versus-host disease: a new
      immunovirological approach.
AB  - In leukemic mice, the native host's explicit and well-defined immune reactions to
      the leukemia virus (a strong exogenous antigen) and to leukemia cells (pretending
      in their native hosts to be protected "self" elements) are extinguished and
      replaced in GvHD (graft-versus-host disease) by those of the immunocompetent
      donor cells. In many cases, the GvHD-inducer donors display genetically encoded
      resistance to the leukemia virus. In human patients only antileukemia and anti
      tumor cell immune reactions are mobilized; thus, patients are deprived of immune
      reactions to a strong exogenous antigen (the elusive human leukemia-sarcoma
      retroviruses). The innate and adaptive immune systems of mice have to sustain the
      immunosuppressive effects of leukemia-inducing retroviruses. Human patients due
      to the lack of leukemiainducing retroviral pathogens (if they exist, they have
      not as yet been discovered), escape such immunological downgrading. After
      studying leukemogenic retroviruses in murine and feline (and other mammalian)
      hosts, it is very difficult to dismiss retroviral etiology for human leukemias
      and sarcomas. Since no characterized and thus recognized leukemogenic
      sarcomagenic retroviral agents are being isolated from the vast majority of human
      leukemias-sarcomas, the treatment for these conditions in mice and in human
      patients vastly differ. It is immunological and biological modalities (alpha
      interferons; vaccines; adoptive lymphocyte therapy) that dominate the treatment
      of murine leukemias, whereas combination chemotherapy remains the main remission
      inducing agent in human leukemias-lymphomas and sarcomas (as humanized monoclonal
      antibodies and immunotoxins move in). Yet, in this apparently different
      backgrounds in Mus and Homo, GvHD, as a treatment modality, appears to work well
      in both hosts, by replacing the hosts' anti-leukemia and anti-tumor immune
      faculties with those of the donor. The clinical application of GvHD in the
      treatment of human leukemias-lymphomas and malignant solid tumors remains a force
      worthy of pursuit, refinement and strengthening. Graft engineering and
      modifications of the inner immunological environment of the recipient host by the
      activation or administration of tumor memory T cells, selected Treg cells and
      natural killer (NKT) cell classes and cytokines, and the improved pharmacotherapy
      of GvHD without reducing its antitumor efficacy, will raise the value of GvHD to
      the higher ranks of the effective antitumor immunotherapeutical measures.
      Clinical interventions of HCT/HSCT (hematopoietic cell/stem cell transplants) are
      now applicable to an extended spectrum of malignant diseases in human patients,
      being available to elderly patients, who receive non-myeloablative conditioning,
      are re-enforced by post-transplant donor lymphocyte (NK cell and immune T cell)
      infusions and post-transplant vaccinations, and the donor cells may derive from
      engineered grafts, or from cord blood with reduced GvHD, but increased GvL/GvT
      inducing capabilities (graft-versus leukemia/tumor). Post-transplant T cell
      transfusions are possible only if selected leukemia antigen-specific T cell
      clones are available. In verbatim quotation: "Ultimately, advances in separation
      of GvT from GvHD will further enhance the potential of allogeneic HCT as a
      curative treatment for hematological malignancies" (Rezvani, A.R. and Storb,
      R.F., Journal of Autoimmunity 30:172-179, 2008 (see in the text)). It may be
      added: for cure, a combination of the GvL/T effects with new targeted therapeutic
      modalities, as elaborated on in this article, will be necessary.

PMID- 21183422
TI  - Herpesvirus-associated lymphomas: Investigations in humans and animal models.
AB  - Lymphomas are solid tumors consisting of lymphoid cells; they form a
      heterogeneous group of less or more malignant disorders. A portion of lymphomas
      develop due to latent herpesvirus infections established in B and/or T
      lymphocytes. The basis for latency is a lifelong presence of the circularized
      covalently linked viral genome within nuclei of carrier lymphocytes. In certain
      cases, however, the essential event leading to tumor formation is the integration
      of a portion(s) of viral DNA into the host cell DNA. This leads to rearrangements
      within the host cell genome on one hand, and, on other hand, to unregulated
      expression of oncoproteins encoded by the integrated fragment. Our review deals
      with mechanisms of lymphoma formation regarding to the role of non-structural
      herpesvirus oncoproteins interfering with the regulation of cell division and/or
      exerting anti-apoptotic effects. In addition, the authors wish to highlight the
      common procedures, which allowed isolation and/or identification of lymphoma
      associated viruses in cell cultures derived from tumors and/or proliferating
      lymphatic tissues.

PMID- 21183423
TI  - Response surface methodology for lovastatin production by Aspergillus terreus
      GD13 strain.
AB  - A wild type Aspergillus terreus GD13 strain, chosen after extensive screening,
      was optimized for lovastatin production using statistical Box-Behnken design of
      experiments. The interactive effect of four process parameters, i.e. lactose and
      soybean meal, inoculum size (spore concentration) and age of the spore culture,
      on the production of lovastatin was evaluated employing response surface
      methodology (RSM). The model highlighted the positive effect of soybean meal
      concentration and inoculum level for achieving maximal level of lovastatin (1342
      mg/l). The optimal fermentation conditions improved the lovastatin titre by 7.0
      folds when compared to the titres obtained under unoptimized conditions.

PMID- 21183425
TI  - Case of Legionella pneumonia complicated with pulmonary thromboembolism.
AB  - We report a patient with community acquired Legionella pneumonia, complicated
      with pulmonary embolism. The patient was cured by levofloxacin and anticoagulant
      therapy. We performed laboratorial control and we excluded the thrombophilia and
      antiphospholipid syndrome. Our case report draws attention to the possible
      association between Legionella infection and pulmonary embolism.

PMID- 21183424
TI  - Hormonal effects on Tetrahymena: change in case of combined treatment.
AB  - In order to approach their natural conditions, populations of Tetrahymena were
      kept in Losina-Losinky's salt solution for 1 h, than in the tryptone+yeast
      medium. During this time they were treated with histamine, serotonin or insulin,
      or with the combinations of these hormones. Effect of the combined treatments on
      the production of serotonin (5HT), or adrenocorticotropic hormone (ACTH) or
      triiodothyronine (T3) by the cells was compared to the effect of single-hormone
      treatments. Significant differences were seen between the results obtained
      following the single or combined treatments. There was no summation of the
      effects, however an elevation or diminution of the hormone production was
      observed after the combined treatment, as compared with the untreated controls or
      with the use of one of the hormones in the samples. The experiments demonstrate
      that there is a hormonal regulation between the Tetrahymena cells and the
      hormones influence each other's effect.

PMID- 21183426
TI  - Clinical microbiology of neonatal candidiasis in Hungary.
AB  - The occurrence of Candida spp. was investigated during a three-year period in two
      neonatal intensive care units, Budapest, Hungary. The species distribution among
      the 41 analysed cases was the following: C. albicans (30/41, 73%), C.
      parapsilosis (10/41, 24%) and C. glabrata (1/41, 3%). All of the isolates were
      susceptible to the tested drugs. There was a significant difference in the birth
      weight, the gestational age <30 weeks and the occurrence of caesarean section
      between the C. albicans and the C. parapsilosis groups of the cases. Respiratory
      tract colonization was the same (76-77%) in the extremely low birth weight (ELBW)
      and the very low birth weight (VLBW) groups. Comparing the ELBW, VLBW, and >1500
      g birth weight groups, significant difference was found in the parenteral
      nutrition, the gestation weeks <36 or <30, the polymicrobial infection and the
      transfusion. The ratio of C. albicans, C. parapsilosis and C. glabrata was 9:7:1
      in ELBW group; 6:3:0 in VLBW group and 15:1:0 in >1500 g group. The mortality
      rate for C. parapsilosis was higher than for C. albicans.

PMID- 21183427
TI  - Cell type specific expression of the apoptosis stimulating protein (ASPP-2) in
      human tissues.
AB  - Apoptosis stimulating proteins of p53 (ASPP-l and ASPP-2) are a novel family of
      proteins that have been found to co-stimulate p53 activation of Bax (Bcl-2
      associated protein X) inducing caspase-mediated apoptosis. Therefore, these
      proteins may play an important role in regulating apoptosis in normal and
      neoplastic cells. However, their cellular and tissue distribution has not been
      documented. The aim of this study was to determine the localization pattern of
      ASPP-2 in a variety of normal and malignant human tissues, including liver, lung,
      prostate, small intestine, kidney, ovary, bladder, cervix, breast, stomach,
      bowel, gallbladder, endometrium, pancreas, spleen and thyroid.The distribution
      and expression of ASPP-2 was assessed by immunohistochemistry in a range of
      formalin-fixed, paraffin embedded, benign and malignant human tissues, using a
      mouse monoclonal antibody against ASPP-2.The results showed a variable pattern of
      positivity of ASPP-2 within the tissues studied. ASPP-2 expression was localized
      in the cytoplasmic paranuclear granules in the epithelial cells of most of the
      organs we studied. The pattern of staining intensity of ASPP-2 correlated to the
      maturation state in benign tissue and to the differentiation state in the context
      of bladder cancer.This study indicates that ASPP-2 has a specific distribution
      pattern within tissues and cells in a way that appears to be related to
      differentiation. However, the patterns are neither simplistic nor straightforward
      and will require further investigation in order to appreciate fully their
      physiological/pathological significance.

PMID- 21183429
TI  - Determination of benzodiazepines in urine via benzophenone derivatives using
      liquid chromatography-tandem mass spectrometry.
AB  - The aim of this study was to validate a new method for determining
      benzodiazepines in urine via their benzophenone derivatives, based on liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). Selected benzodiazepines were
      analysed after acid hydrolysis of urine and extraction by ethyl acetate in the
      presence of an internal standard. Samples were analysed using electrospray
      ionization LC-MS/MS in a multiple reaction monitoring mode. The chromatographic
      run time on a reversed phase C18 analytical column was set for 9 min. This method
      was validated in 21 patients receiving methadone. Benzodiazepines intake was
      established in two out of three patients. LC-MS/MS results were also compared
      with the rapid immunoassay and the methods showed good agreement. However, in
      three cases benzodiazepines were detected by LC-MS/MS, but not by the
      immunoassay. The sensitivity of the developed LC-MS/MS method is comparable to or
      even higher than of previously reported methods, which makes it suitable as a
      confirmatory method.

PMID- 21183430
TI  - Determination of biogenic amines and endotoxin in squid, musky octopus, Norway
      lobster, and mussel stored at room temperature.
AB  - Little research has been published on the indicators of spoilage in Mediterranean
      molluscan shellfish and crustaceans. Thus is why we studied changes in the
      concentrations of endotoxin and four biogenic amines (histamine, putrescine,
      tyramine and cadaverine) in European common squid (Loligo subulata, Lamarck,
      1798), musky octopus (Eledone moschata, Lamarck, 1798), Norway lobster (Nephrops
      norvegicus, Linnaeus, 1758), and mussel (Mytilus galloprovincialis, Lamarck,
      1819) from the Adriatic Sea stored at room temperature for 24 h. Endotoxin load
      in fresh squid, Norway lobster, and mussel (<1 EU mg-1) indicated good
      microbiological quality of raw samples. Biogenic amine index (as the sum of
      histamine, putrescine, tyramine, and cadaverine) correlated well with endotoxin
      load in squid (r=0.978, p<0.001) and musky octopus (r=0.874, p<0.01). A good
      correlation was also found between endotoxin and putrescine in Norway lobster
      (r=0.777, p<0.05). The highest endotoxin load was found in decomposed mussels and
      was associated with histamine alone. In conclusion, increase in biogenic amine
      levels is species-specific. Endotoxin analysis could be used for rapid assessment
      of microbiological quality of cephalopods and shellfish.

PMID- 21183431
TI  - Biodegradation of olive mill wastewater by Trichosporon cutaneum and Geotrichum
      candidum.
AB  - Olive oil production generates large volumes of wastewater. These wastewaters are
      characterised by high chemical oxygen demand (COD), high content of microbial
      growth-inhibiting compounds such as phenolic compounds and tannins, and dark
      colour. The aim of this study was to investigate biodegradation of olive mill
      wastewater (OMW) by yeasts Trichosporon cutaneum and Geotrichum candidum. The
      yeast Trichosporon cutaneum was used because it has a high potential to
      biodegrade phenolic compounds and a wide range of toxic compounds. The yeast
      Geotrichum candidum was used to see how successful it is in biodegrading
      compounds that give the dark colour to the wastewater. Under aerobic conditions,
      Trichosporon cutaneum removed 88 % of COD and 64 % of phenolic compounds, while
      the dark colour remained. Geotrichum candidum grown in static conditions reduced
      COD and colour further by 77 % and 47 %, respectively. This investigation has
      shown that Trichosporon cutaneum under aerobic conditions and Geotrichum candidum
      under facultative anaerobic conditions could be used successfully in a two-step
      biodegradation process. Further investigation of OMW treatment by selected yeasts
      should contribute to better understanding of biodegradation and decolourisation
      and should include ecotoxicological evaluation of the treated OMW.

PMID- 21183432
TI  - Performance of fine motor and spatial tasks during the menstrual cycle.
AB  - Various studies have shown fluctuations in task performance during the menstrual
      cycle. The aim of this study was to see the effects of the menstrual cycle on
      performing fine motor and spatial tasks of different level of complexity in
      twenty students aged 18 to 21 years, with regular menstrual cycle (28 to 30
      days). The students performed O'Connor Finger Dexterity Test and mental rotation
      test during the menstrual, late follicular, and midluteal phase. Before the tests
      were performed, we administered Spielberger's State-Trait Anxiety Inventory for
      each phase. After the tasks were completed, the subjects ranked their difficulty
      on Borg's scale.The results showed the best performance in both tests in the
      midluteal phase (with sex hormones at their peak). The anxiety level and task
      difficulty ranking were the highest in the menstrual phase, when the hormone
      levels were the lowest.

PMID- 21183433
TI  - Environmental and occupational health risks among agricultural workers living in
      a rural community near petroleum refinery and motorway in Skopje region.
AB  - To assess health risks in agricultural workers associated with environmental
      exposure to pollutants released from a petroleum refinery and from traffic, we
      performed a cross-sectional study that included 119 randomly selected subjects
      divided in two groups. Group 1 included 60 agricultural workers living in a rural
      community near the petroleum refinery and a motorway overpass, whereas Group 2
      consisted of 59 agricultural workers performing similar activities and living in
      a rural community with no exposure to industrial and traffic pollutants. Risk
      assessment included a questionnaire, blood pressure measurement, spirometry,
      laboratory tests, and toxicological analysis. The groups showed a similar
      prevalence of health problems, with exception of muscle pain in the extremities,
      headache, and fatigue, which were significantly more common in Group 1. Diastolic
      blood pressure was higher in Group 1, but not significantly (p=0.057). The same
      is true for blood carbon monoxide. Significantly higher in Group 1 were blood
      haemoglobin (p=0.001) and blood lead (p<0.001). Serum cholinesterase activity was
      similar in both groups. Our findings indicate the need of regular medical exams,
      ambient monitoring and environmental impact assessment in agricultural population
      in order to detect individuals at risk and to institute adequate preventive
      measures.

PMID- 21183434
TI  - Good manufacturing practice: the role of local manufacturers and competent
      authorities.
AB  - In every country, a manufacturer of medicinal products for either human or
      veterinary use is required to operate in compliance with local legislation. In
      all EU Member States, legislation is approximated to the effect that they are
      committed to abide by the same standards. The candidate countries transpose the
      acquis into their national legislation, including the good manufacturing practice
      (GMP). Consequently, the local manufacturer is required to strictly comply with
      GMP and the manufacturing licence, including for medicinal products exclusively
      intended for export. A vital role is also played by national regulatory
      authorities, in Croatia by the Agency for Medicinal Products and Medical Devices
      which issues the manufacturing licence, GMP certificate, and the Certificate of a
      Pharmaceutical Product (CPP) and conducts laboratory control of products. GMP
      inspection is carried out by the Pharmaceutical Inspectorate with the Ministry of
      Health and Social Welfare. Both authorities are responsible only for human
      medicines. There are legislative issues not yet harmonised with the acquis, but
      as a country aspiring for the EU membership, Croatia is expected to demonstrate
      that its industry and competent authorities are able to conform to current
      requirements and thus fully adhere to the integrated European regulatory network.
      Hence the importance of strengthening the institutional capacity of the competent
      authorities, as insufficient resources may have a direct bearing on patients by
      limiting their access to affordable treatment.

PMID- 21183435
TI  - Quality control of seasonal influenza vaccines.
AB  - The purpose of seasonal influenza vaccination is to prevent its spread. The
      vaccines contain strains of the influenza virus recommended and approved for a
      particular season. Just like any other medicinal product, all vaccines require
      marketing approval. Batches of approved vaccines are extensively tested by the
      manufacturers and additionally controlled by the approving authorities, which
      issue the quality control certificates. This article not only to describes the
      legal background of quality control, but also how control test results obtained
      by a Croatian official control laboratory are compared to manufacturer's results.
      We have found that testing results can slightly differ depending on
      methods/analytical procedures used in different laboratories. This investigation
      has also shown how important it is to test finished medicinal products,
      independently of testing at intermediate stages, and how retesting by control
      authorities ensures that marketed vaccines meet quality standards.

PMID- 21183436
TI  - Dioxins and human toxicity.
AB  - The term dioxins usually refers to polychlorinated dibenzo-dioxins (PCDDs) and
      polychlorinated dibenzofurans (PCDFs). As 2,3,7,8-tetrachloro-dibenzo-p-dioxin
      (TCDD) has the highest toxic potential, the toxic potentials of other PCDDs and
      PCDFs are defined in comparison with it. Human exposure to dioxins can be
      environmental (background), occupational, or accidental pollution. In the human
      body, dioxins are in part metabolised and eliminated, and the rest is stored in
      body fat. People vary in their capacity to eliminate TCDD, but it is also dose
      dependent; the elimination rate is much faster at higher than lower levels. The
      liver microsomal P4501A1 enzyme oxygenates lipophilic chemicals such as dioxins.
      It is encoded by the CYP1A1 gene. Cytosolic aryl hydrocarbon receptor (AhR)
      mediates their carcinogenic action. It binds to dioxin, translocates to nucleus
      and together with hydrocarbon nuclear translocator (ARNT) and xenobiotic
      responsive element (XRE) increases the expression of CYP1A1.Dioxins are
      classified as known human carcinogens, but they also cause noncancerous effects
      like atherosclerosis, hypertension, and diabetes. Long-term exposures to dioxins
      cause disruption of the nervous, immune, reproductive, and endocrine system.
      Short-term exposure to high levels impairs the liver function and causes
      chloracne. The most sensitive population to dioxin exposure are the foetuses and
      infants.A large number of health effects have been documented in the scientific
      literature, and they all place dioxins among the most toxic chemicals known to
      man.

PMID- 21183437
TI  - Prenatal, early life, and childhood exposure to genotoxicants in the living
      environment.
AB  - Health disorders and diseases related to environmental exposure in children such
      as cancer and immunologic disturbances (asthma, allergies) are on the rise.
      However, complex transplacental and prepubertal genotoxicology is given very
      limited consideration, even though intrauterine development and early childhood
      may be critical for elucidating the cancer aetiology. The foetus is
      transplacentally exposed to contaminants in food and environment such as various
      chemicals, drugs, radiochemically contaminated water and air. Target organs of
      xenobiotic action may differ between the mother and the foetus due to specific
      stage of developmental physiology and enzyme distribution. This in turn may lead
      to different levels of clastogenic and aneugenic metabolites of the same
      xenobiotic in the mother and the foetus. Adult's protective behaviour is not
      sufficient to isolate children from radioisotopes, pesticides, toxic metals and
      metalloids, environmental tobacco smoke, endocrine disrupting chemicals, and
      various food contaminants, which are just a part of the stressors present in a
      polluted environment. In order to improve legislation related to foetus and child
      exposure to genotoxic and possibly carcinogenic agents, oncologists,
      paediatricians, environmental health specialists, and genotoxicologists should
      work together much more closely to make a more effective use of accumulated
      scientific data, with the final aim to lower cancer incidence and mortality.

PMID- 21183438
TI  - [Shiftwork problems].
AB  - This paper discusses the negative effects of shiftwork which are classified into
      four categories: biological functions, efficiency, social/family domains and
      health. It presents systematic review of previous studies which indicated at
      health problems in shiftworkers which can, at least in part, be attributed to
      disturbation of circadian rhythms imposed by shift/night work. Health problems
      which are connected with shiftwork are: sleeping problems, gastrointestinal and
      cardiovascular diseases, carcinoma, problems with reproductive health in women
      and lower levels of psychological health.The paper also discusses about shiftwork
      tolerance. The process model of shiftwork and health, made by Smith and his
      coworkers in 1999, is used as theoretical framework. An accent is put on
      individual and organisational factors which are important for shiftwork
      adaptation and tolerance. Significant predictors of shiftwork tolerance are: age,
      gender, morningness-eveningness, rigidity-flexibility of sleeping habits, family
      situation, sleep hygiene and food intake. Regarding studies which indicated
      important aspects of shiftwork organization, such as: number of working shifts
      and working hours, regularity of shifts, pace and direction of shifts' rotation,
      recommendations for shiftwork management are given.

PMID- 21183439
TI  - [Dragutin Mayer and Bozo Metzger: leaders in radiation science and radiation
      protection in Croatia].
AB  - Soon after Rontgen described X-rays (in many languages also known as Rontgen
      rays) in end 1895, information about their use in medicine and science came to
      Croatia and first roentgenograms and Rontgen tubes were acquired by the beginning
      of the year 1896. That same year saw the first demonstration of X-rays and the
      effective beginning of radiation science in Croatia.This article speaks about,
      the work of Bozo Metzger and the late Dragutin Mayer, two remarkable radiation
      scientists from Croatia. Both had a unique role in teaching radiation protection
      and physics at a university level. Their recollections reveal many unknown
      details about the history of radiation science and radiation protection in
      Croatia.

PMID- 21183440
TI  - Zooxanthellar symbionts shape host sponge trophic status through translocation of
      carbon.
AB  - Sponges belonging to the genus Cliona are common inhabitants of many coral reefs,
      and as bioeroders, they play an important role in the carbonate cycle of the
      reef. Several Cliona species maintain intracellular populations of dinoflagellate
      zooxanthellae (i.e., Symbiodinium spp.), which also form symbioses with a variety
      of other invertebrates and protists (e.g., corals, molluscs, foraminifera).
      Unlike the case of coral symbioses, however, almost nothing is known of the
      metabolic interaction between sponges and their zooxanthella symbionts. To assess
      this interaction, we performed a tracer experiment to follow C and N in the
      system, performed a reciprocal transplant experiment, and measured the stable
      carbon isotope ratio of Cliona spp. with and without zooxanthellae to study the
      influence of environment on the interaction. We found strong evidence of a
      transfer of C from zooxanthellae to their sponge hosts but no evidence of a
      transfer of N from sponge to zooxanthellae. We also saw significant influences of
      the environment on the metabolism of the sponges. Finally, we observed
      significant differences in carbon metabolism of sponge species with and without
      symbionts. These data strongly support hypotheses of metabolic integration
      between zooxanthellae and their sponge host and extend our understanding of basic
      aspects of benthic-pelagic coupling in shallow-water marine environments.

PMID- 21183441
TI  - Influence of sperm and phytoplankton on spawning in the echinoid Lytechinus
      variegatus.
AB  - The cues triggering large-scale broadcast-spawning events in marine invertebrates
      are not fully understood. Using the sea urchin Lytechinus variegatus, we tested
      the effectiveness of a variety of potential spawning cues in eliciting a spawning
      response. In the laboratory, during two consecutive spawning seasons, about 400
      isolated sea urchins were exposed to phytoplankton, sperm, or eggs, singly or in
      combination. The likelihood of spawning, time to spawning, and spawning behavior
      were recorded for both sexes. Sperm was most successful at inducing spawning. No
      response to eggs was noted. Phytoplankton alone did not trigger spawning, but
      when a phytoplankton cue was followed by the addition of sperm, spawning behavior
      was induced, the time between addition of sperm and spawning was reduced, and the
      variance among individuals in the time of spawning initiation was reduced. Males
      spawned sooner in response to cues than females and rarely spawned spontaneously
      in phytoplankton or control treatments. A semilunar pattern in the sensitivity to
      spawning cues was noted. During time periods when sea urchins were less ripe, the
      ratio of spawning males to spawning females increased. Our results indicate that
      seasonal and lunar cycles, together with the presence of phytoplankton, increase
      the sensitivity of these sea urchins to spawning cues and the precision of their
      responses to conspecific sperm.

PMID- 21183442
TI  - Proximate control of diel vertical migration in Phyllosoma larvae of the
      Caribbean spiny lobster Panulirus argus.
AB  - Phyllosoma larvae of the spiny lobster Panulirus argus undergo diel vertical
      migration (DVM), in which they are at depth during the day and nearer the surface
      at night. This study determined the visual spectral sensitivity of Stage I larvae
      and investigated whether light plays a proximate role in DVM as an exogenous cue
      and as an entrainment cue for an endogenous rhythm in vertical migration. Under
      constant conditions, larvae have a circadian rhythm (24.5-h period) in vertical
      swimming that resulted in a twilight DVM pattern. The behavioral response
      spectrum and electroretinogram recording indicated two photoreceptor spectral
      classes with maxima at 360 and 486 nm. When stimulated in an apparatus that
      simulated the underwater angular light distribution, dark-adapted larvae showed
      only positive phototaxis, with a threshold intensity of 1.8 * 10(13) photons m(
      2) s(-1) (3.0 * 10(-5) MUmoles photons m(-2) s(-1)). They have an avoidance
      response to predator shadows in which they descend upon sudden decreases in light
      intensity of more than 69%. When stimulated with relative rates of decrease in
      light intensity as occur at sunset they ascended, whereas they descended upon
      relative rates of light intensity increase as occur at sunrise. Thus, the DVM
      pattern is controlled by both an endogenous circadian rhythm in swimming and
      behavioral responses to light at sunrise and sunset.

PMID- 21183443
TI  - Does polymorphism predict physiological connectedness? A test using two
      encrusting bryozoans.
AB  - A colonial lifestyle necessitates communication between colony members to
      coordinate functions and enable resource sharing through physiological
      integration. Colonial integration is predicted to increase with both the size of
      the colony and the level of specialization (polymorphism). In modular colonies,
      although integration might be reflected in structural characteristics such as
      module spacing or branching patterns, physiological integration is fundamentally
      dependent on the level of connectedness between modules. In cheilostome
      bryozoans, funicular tissue links adjacent zooids through pores within zooid
      walls and is the most likely means of nutrient transport within colonies. We
      sought to determine whether the relative numbers of pores (septulae) and pore
      plates (septal chambers) per zooid differed across colony regions in a
      monomorphic species, Watersipora subtorquata, and one showing some polymorphism,
      Mucropetraliella ellerii. Within each species, the morphology of pore plates
      corresponded to functional predictions based on their position within the zooid,
      and connection numbers per zooid increased with colony size. Contrary to
      expectations, however, the more complex species, M. ellerii, had significantly
      fewer porous connections per zooid than W. subtorquata. Physiological
      connectedness was therefore not predicted by simple assessment of polymorphism in
      these species and may not be sufficient to infer colonial integration in related
      taxa.

PMID- 21183444
TI  - Spikey bivalves: intra-periostracal crystal growth in anomalodesmatans.
AB  - The external shell surfaces of most anomalodesmatan bivalves are studded with
      small spikes, particularly at the posterior end. We have studied the morphology,
      mode of growth, and distribution among taxa of these spikes. In this study we
      found that spikes vary widely in morphology, from acute spikes to flat plaques.
      Optical and electron microscopy has revealed that the periostraca of Laternula,
      Myadora, and Thraciopsis consist of an outer dense layer and an inner translucent
      layer. The dense layer grows at the expense of the inner layer as it progresses
      toward the shell edge. The spikes begin to grow in the free periostracum, within
      the translucent periostracal layer, immediately below the dense layer. With
      growth, they push the dense periostracal layer upward but without penetrating it.
      Those parts of the spike in contact with this layer cease to grow, which explains
      the typical conical shape of spikes. When fully grown, spikes reach the base of
      the translucent layer, becoming incorporated into the outer shell layer. Scanning
      electron microscopy and electron backscatter diffraction analysis reveal that the
      spikes of Lyonsia norwegica and Lyonsiella abyssicola are prisms of aragonite
      composed of twinned crystals, with the c-axis vertical. A survey of the
      occurrence of spikes within the anomalodesmatans shows that they are present in
      all but a few families. Elsewhere within the closely related palaeoheterodonts,
      intra-periostracal calcification is also known in Neotrigonia and unionids, which
      indicates that this character may be plesiomorphic for these bivalves. The
      present data do not support the homology of spikes in other bivalve groups (e.g.,
      veneroids) or in the aplacophorans or polyplacophorans.

PMID- 21183445
TI  - New family of allomorphic jellyfishes, Drymonematidae (Scyphozoa, Discomedusae),
      emphasizes evolution in the functional morphology and trophic ecology of
      gelatinous zooplankton.
AB  - Molecular analyses have revealed many cryptic species in the oceans, often
      permitting small morphological differences to be recognized as diagnosing
      species, but less commonly leading to consideration of cryptic ecology. Here,
      based on analyses of three nuclear DNA sequence markers (ribosomal 18S, 28S, and
      internal transcribed spacer 1 [ITS1]), two mitochondrial DNA markers (cytochrome
      c oxidase subunit I [COI] and ribosomal 16S), and 55 morphological features, we
      revise the classification of the enigmatic jellyfish genus Drymonema. We describe
      a new scyphozoan family, Drymonematidae, elevating the previous subfamily
      Drymonemidae to accommodate three species: the type species D. dalmatinum from
      the Mediterranean region, for which we identify a neotype; the western South
      Atlantic species D. gorgo; and a new species, D. larsoni from the western
      Atlantic and Caribbean, which also is described here. This revision emphasizes
      the remarkable morphological disparity of Drymonematidae from all other
      scyphomedusae, including allometric growth of the bell margin distal of the
      rhopalia, an annular zone of tentacles on the subumbrella, and ontogenetic loss
      of gastric filaments. Anatomical innovations are likely functionally related to
      predatory specialization on large gelatinous zooplankton, most notably the
      phylogenetically younger moon jellyfish Aurelia, indicating evolution of the
      feeding niche in Drymonematidae. This family-level revision contributes to the
      growing body of evidence that scyphomedusae are far more taxonomically rich,
      their biogeography is a more detailed mosaic, and their phenotypes are more
      nuanced than traditionally thought. Ecological and evolutionary responses to
      environmental change, past or future, are likely to be commensurately diverse.

PMID- 21183446
TI  - Refuge from predation, the benefit of living in an extreme acidic environment?
AB  - Organisms living in extreme habitats require costly adaptations to cope with
      these conditions. Among the suggested potential benefits that trade off these
      costs is refuge from predation. To study these interactions in extreme
      environments, samples were taken in the cave Cueva de Villa Luz, Tabasco, Mexico,
      where more than 32 subterranean springs, some H(2)S rich, rise from the floor.
      Hydrogen sulfide gas plus oxygen is absorbed by freshwater, and oxidation forms
      concentrated sulfuric acid. Snottites, whitish hollow mucous tubes, hang from the
      ceiling of the cave. Fluid drops from these snottites were recorded as having pH
      values of 0-3. We report the discovery of a new species of nematode that thrives
      in the highly acidic environment of the snottite. Micro CT scan of snottites
      reveals a complex interaction between the acidic snottite, nematodes, and
      abundant nematode-eating mites. The nematode adaptation to low pH probably
      protects them against mite predation, for which nematodes are most likely the
      most important source of carbon in this sulfur-driven ecosystem.

PMID- 21183447
TI  - Molgula pugetiensis is a Pacific tailless ascidian within the Roscovita clade of
      molgulids.

PMID- 21183448
TI  - Comparison of control of pedal sole cilia in the snails Lymnaea stagnalis
      appressa and Helisoma trivolvis.

PMID- 21183450
TI  - Regression of lymphoma after withdrawal of infliximab alone in an
      infliximab/methotrexate-treated RA patient.

PMID- 21183451
TI  - Unnecessary radiation exposure from medical imaging in the rheumatology patient.

PMID- 21183452
TI  - Pregnancies in systemic necrotizing vasculitides: report on 12 women and their 20
      pregnancies.
AB  - OBJECTIVES: To describe pregnancies of women with systemic necrotizing
      vasculitides (SNVs), i.e. PAN, WG, Churg-Strauss syndrome (CSS) or microscopic
      polyangiitis (MPA), followed over the past 15 years at four French centres.
      METHODS: Retrospective analysis of women whose SNV appeared during pregnancy or
      who became pregnant after SNV diagnosis. RESULTS: Among the 12 women identified,
      one experienced rupture of pancreatic artery microaneurysms at 27 weeks revealing
      PAN, leading to surgical haemostasis and caesarean delivery. Eleven others
      started 19 pregnancies after SNV diagnosis (8 in four WG, 6 in three CSS, 1 each
      in three PAN and 2 in one MPA); 14 conceived during vasculitis remission. Two
      ended in first-trimester abortions, four miscarried; the remaining 13 pregnancies
      yielded 14 live newborns (1 twin pregnancy), with 7 pre-term births. Life
      threatening complications occurred during 3 of these latter 13 pregnancies and
      required caesarean delivery. The twin pregnancy (in a CSS patient with initial
      vasculitis-related cardiac involvement, but in remission at conception) was
      complicated by transient maternal cardiac failure at 32 weeks. One WG patient
      with vasculitis-related renal damage developed thrombotic microangiopathy
      associated renal impairment at 32 weeks, and another WG patient had severe
      pneumonia at 37 weeks. Other pregnancies were uneventful or with minor vasculitis
      manifestations. CONCLUSION: Pregnant SNV patients should be monitored closely,
      because miscarriages and pre-term births are not uncommon. Pregnancy does not
      seem to have a major impact on vasculitis activity. However, life-threatening
      manifestations can occur, especially in patients with vasculitis-related cardiac
      or renal damage.

PMID- 21183453
TI  - Correlation between dynamic tomato fruit-set and source-sink ratio: a common
      relationship for different plant densities and seasons?
AB  - BACKGROUND AND AIMS: It is widely accepted that fruit-set in plants is related to
      source-sink ratio. Despite its critical importance to yield, prediction of fruit
      set remains an ongoing problem in crop models. Functional-structural plant models
      are potentially able to simulate organ-level plasticity of plants. To predict
      fruit-set, the quantitative link between source-sink ratio and fruit-set
      probability is analysed here via a functional-structural plant model, GreenLab.
      METHODS: Two experiments, each with four plant densities, were carried out in a
      solar greenhouse during two growth seasons (started in spring and autumn).
      Dynamic fruit-set probability was estimated by frequent observation on
      inflorescences. Source and sink parameter values were obtained by fitting
      GreenLab outputs for the biomass of plant parts (lamina, petiole, internode,
      fruit), at both organ and plant level, to corresponding destructive measurements
      at six dates from real plants. The dynamic source-sink ratio was calculated as
      the ratio between biomass production and plant demand (sum of all organ sink
      strength) per growth cycle, both being outputs of the model. KEY RESULTS AND
      CONCLUSIONS: Most sink parameters were stable over multiple planting densities
      and seasons. From planting, source-sink ratio increased in the vegetative stage
      and reached a peak after fruit-set commenced, followed by a decrease of leaf
      appearance rate. Fruit-set probability was correlated with the source-sink ratio
      after the appearance of flower buds. The relationship between fruit-set
      probability and the most correlated source-sink ratio could be quantified by a
      single regression line for both experiments. The current work paves the way to
      predicting dynamic fruit-set using a functional structure model.

PMID- 21183454
TI  - Genotypic differences in Al resistance and the role of cell-wall pectin in Al
      exclusion from the root apex in Fagopyrum tataricum.
AB  - BACKGROUND AND AIMS: Aluminium (Al) toxicity is one of the factors limiting crop
      production on acid soils. However, genotypic differences exist among plant
      species or cultivars in response to Al toxicity. This study aims to investigate
      genotypic differences among eight cultivars of tatary buckwheat (Fagopyrum
      tataricum) for Al resistance and explore the possible mechanisms of Al
      resistance. METHODS: Al resistance was evaluated based on relative root
      elongation (root elongation with Al/root elongation without Al). Root apex Al
      content, pectin content and exudation of root organic acids were determined and
      compared. KEY RESULTS: Genotypic differences among the eight cultivars were
      correlated with exclusion of Al from the root apex. However, there was a lack of
      correlation between Al exclusion and Al-induced oxalate secretion. Interestingly,
      cell-wall pectin content of the root apex was generally lower in Al-resistant
      cultivars than in Al-sensitive cultivars. Although we were unable to establish a
      significant correlation between Al exclusion and pectin content among the eight
      cultivars, a strong correlation could be established among six cultivars, in
      which the pectin content in the most Al-resistant cultivar 'Chuan' was
      significantly lower than that in the most Al-sensitive cultivar 'Liuku2'.
      Furthermore, root apex cell-wall pectin methylesterase activity (PME) was similar
      in 'Chuan' and 'Liuku2' in the absence of Al, but Al treatment resulted in
      increased PME activity in 'Liuku2' compared with 'Chuan'. Immunolocalization of
      pectins also showed that the two cultivars had similar amounts of either low
      methyl-ester pectins or high-methyl-ester pectins in the absence of Al, but Al
      treatment resulted in a more significant increase of low-methyl-ester pectins and
      decrease of high-methyl-ester pectins in 'Liuku2'. CONCLUSIONS: Cell-wall pectin
      content may contribute, at least in part, to differential Al resistance among
      tatary buckwheat cultivars.

PMID- 21183455
TI  - Comparative anatomy of the nectary spur in selected species of Aeridinae
      (Orchidaceae).
AB  - BACKGROUND AND AIMS: To date, the structure of the nectary spur of Aeridinae has
      not been studied in detail, and data relating to the nectaries of ornithophilous
      orchids remain scarce. The present paper compares the structural organization of
      the floral nectary in a range of Aeridinae species, including both entomophilous
      and ornithophilous taxa. METHODS: Nectary spurs of Ascocentrum ampullaceum
      (Roxb.) Schltr. var. aurantiacum Pradhan, A. curvifolium (Lindl.) Schltr., A.
      garayi Christenson, Papilionanthe vandarum (Rchb.f.) Garay, Schoenorchis gemmata
      (Lindl.) J.J. Sm., Sedirea japonica (Rchb.f.) Garay & H.R. Sweet and Stereochilus
      dalatensis (Guillaumin) Garay were examined by means of light microscopy,
      scanning electron microscopy and transmission electron microscopy. KEY RESULTS
      AND CONCLUSIONS: The diverse anatomy of the nectary is described for a range of
      Aeridinae species. All species of Ascocentrum investigated displayed features
      characteristic of ornithophilous taxa. They have weakly zygomorphic, scentless,
      red or orange flowers, display diurnal anthesis, possess cryptic anther caps and
      produce nectar that is secluded in a relatively massive nectary spur.
      Unicellular, secretory hairs line the lumen at the middle part of the spur.
      Generally, however, with the exception of Papilionanthe vandarum, the nectary
      spurs of all entomophilous species studied here (Schoenorchis gemmata, Sedirea
      japonica, Stereochilus dalatensis) lack secretory trichomes. Moreover,
      collenchymatous secretory tissue, present only in the nectary spur of Asiatic
      Ascocentrum species, closely resembles that found in nectaries of certain
      Neotropical species that are hummingbird-pollinated and assigned to subtribes
      Maxillariinae Benth., Laeliinae Benth. and Oncidiinae Benth. This similarity in
      anatomical organization of the nectary, regardless of geographical distribution
      and phylogeny, indicates convergence.

PMID- 21183456
TI  - Interaction between trait anxiety and trait anger predict amygdala reactivity to
      angry facial expressions in men but not women.
AB  - The amygdala is critically involved in mediating physiological and behavioral
      responses to threat. In particular, neuroimaging research indicates that the
      amygdala is highly responsive to facial signals of threat such as fearful and
      angry expressions. However, individuals differ substantially in both their
      relative sensitivity to threat and the magnitude of amygdala reactivity to facial
      signals of threat. Here, we report the novel finding that individual differences
      in trait anger are positively correlated with bilateral dorsal amygdala
      reactivity to angry facial expressions, but only among men with elevated trait
      anxiety scores. These findings add to the growing body of evidence indicating
      that variability in personality traits contribute to individual differences in
      threat-related amygdala reactivity and further suggest that heightened amygdala
      reactivity to angry faces may be uniquely involved in the expression of reactive
      aggression in men.

PMID- 21183457
TI  - Time spent with friends in adolescence relates to less neural sensitivity to
      later peer rejection.
AB  - Involvement with friends carries many advantages for adolescents, including
      protection from the detrimental effects of being rejected by peers. However,
      little is known about the mechanisms through which friendships may serve their
      protective role at this age, or the potential benefit of these friendships as
      adolescents transition to adulthood. As such, this investigation tested whether
      friend involvement during adolescence related to less neural sensitivity to
      social threats during young adulthood. Twenty-one adolescents reported the amount
      of time they spent with friends outside of school using a daily diary. Two years
      later they underwent an fMRI scan, during which they were ostensibly excluded
      from an online ball-tossing game by two same-age peers. Findings from region of
      interest and whole brain analyses revealed that spending more time with friends
      during adolescence related to less activity in the dorsal anterior cingulate
      cortex and anterior insula--regions previously linked with negative affect and
      pain processing--during an experience of peer rejection 2 years later. These
      findings are consistent with the notion that positive relationships during
      adolescence may relate to individuals being less sensitive to negative social
      experiences later on.

PMID- 21183459
TI  - Non-coding RNAs: could they be the answer?
AB  - Despite a considerable amount of effort by different groups to evaluate the
      genetic traits associated with complex diseases by genome-wide association
      studies (GWAS), just a few regions, mainly linked to protein-coding genes, were
      identified. Recently, studies from different groups have implicated new classes
      of long non-coding RNAs (ncRNAs) to important molecular mechanisms. Additionally,
      high-throughput transcriptome analyses of different cell types have shown that an
      unexpected amount of genomic DNA is transcribed. I am writing to propose that the
      majority of the regions that do not clearly correspond to a 'gene' controlling
      certain traits might be ncRNAs or other regulatory transcripts that are still
      unknown. These regions will need to be carefully examined in the future.

PMID- 21183458
TI  - How does your own knowledge influence the perception of another person's action
      in the human brain?
AB  - When you see someone reach into a cookie jar, their goal remains obvious even if
      you know that the last cookie has already been eaten. Thus, it is possible to
      infer the goal of an action even if you know that the goal cannot be achieved.
      Previous research has identified distinct brain networks for processing
      information about object locations, actions and mental-state inferences. However,
      the relationship between brain networks for action understanding in social
      contexts remains unclear. Using functional magnetic resonance imaging, this study
      assesses the role of these networks in understanding another person searching for
      hidden objects. Participants watched movie clips depicting a toy animal hiding
      and an actor, who was ignorant of the hiding place, searching in the filled or
      empty location. When the toy animal hid in the same location repeatedly, the
      blood oxygen level-dependent (BOLD) response was suppressed in occipital,
      posterior temporal and posterior parietal brain regions, consistent with
      processing object properties and spatial attention. When the actor searched in
      the same location repeatedly, the BOLD signal was suppressed in the inferior
      frontal gyrus, consistent with the observation of hand actions. In contrast,
      searches towards the filled location compared to the empty location were
      associated with a greater response in the medial prefrontal cortex and right
      temporal pole, which are both associated with mental state inference. These
      findings show that when observing another person search for a hidden object,
      brain networks for processing information about object properties, actions and
      mental state inferences work together in a complementary fashion. This supports
      the hypothesis that brain regions within and beyond the putative human mirror
      neuron system are involved in action comprehension within social contexts.

PMID- 21183461
TI  - Can policy analysis theories predict and inform policy change? Reflections on the
      battle for legal abortion in Indonesia.
AB  - The relevance and importance of research for understanding policy processes and
      influencing policies has been much debated, but studies on the effectiveness of
      policy theories for predicting and informing opportunities for policy change
      (i.e. prospective policy analysis) are rare. The case study presented in this
      paper is drawn from a policy analysis of a contemporary process of policy debate
      on legalization of abortion in Indonesia, which was in flux at the time of the
      research and provided a unique opportunity for prospective analysis. Applying a
      combination of policy analysis theories, this case study provides an analysis of
      processes, power and relationships between actors involved in the amendment of
      the Health Law in Indonesia. It uses a series of practical stakeholder mapping
      tools to identify power relations between key actors and what strategic
      approaches should be employed to manage these to enhance the possibility of
      policy change. The findings show how the moves to legalize abortion have been
      supported or constrained according to the balance of political and religious
      powers operating in a macro-political context defined increasingly by a polarized
      Islamic-authoritarian-Western-liberal agenda. The issue of reproductive health
      constituted a battlefield where these two ideologies met and the debate on the
      current health law amendment became a contest, which still continues, for the
      larger future of Indonesia. The findings confirm the utility of policy analysis
      theories and stakeholder mapping tools for predicting the likelihood of policy
      change and informing the strategic approaches for achieving such change. They
      also highlight opportunities and dilemmas in prospective policy analysis and
      raise questions about whether research on policy processes and actors can or
      should be used to inform, or even influence, policies in 'real-time'.

PMID- 21183462
TI  - Structural and functional analysis of the Rous Sarcoma virus negative regulator
      of splicing and demonstration of its activation by the 9G8 SR protein.
AB  - Retroviruses require both spliced and unspliced RNAs for replication.
      Accumulation of Rous Sarcoma virus (RSV) unspliced RNA depends upon the negative
      regulator of splicing (NRS). Its 5'-part is considered as an ESE binding SR
      proteins. Its 3'-part contains a decoy 5'-splice site (ss), which inhibits
      splicing at the bona fide 5'-ss. Only the 3D structure of a small NRS fragment
      had been experimentally studied. Here, by chemical and enzymatic probing, we
      determine the 2D structure of the entire RSV NRS. Structural analysis of other
      avian NRSs and comparison with all sequenced avian NRSs is in favour of a
      phylogenetic conservation of the NRS 2D structure. By combination of approaches:
      (i) in vitro and in cellulo splicing assays, (ii) footprinting assays and (iii)
      purification and analysis of reconstituted RNP complex, we define a small NRS
      element retaining splicing inhibitory property. We also demonstrate the
      capability of the SR protein 9G8 to increase NRS activity in vitro and in
      cellulo. Altogether these data bring new insights on how NRS fine tune splicing
      activity.

PMID- 21183463
TI  - Unexpected origins of the enhanced pairing affinity of 2'-fluoro-modified RNA.
AB  - Various chemical modifications are currently being evaluated for improving the
      efficacy of short interfering RNA (siRNA) duplexes as antisense agents for gene
      silencing in vivo. Among the 2'-ribose modifications assessed to date, 2'deoxy-2'
      fluoro-RNA (2'-F-RNA) has unique properties for RNA interference (RNAi)
      applications. Thus, 2'-F-modified nucleotides are well tolerated in the guide
      (antisense) and passenger (sense) siRNA strands and the corresponding duplexes
      lack immunostimulatory effects, enhance nuclease resistance and display improved
      efficacy in vitro and in vivo compared with unmodified siRNAs. To identify
      potential origins of the distinct behaviors of RNA and 2'-F-RNA we carried out
      thermodynamic and X-ray crystallographic analyses of fully and partially 2'-F
      modified RNAs. Surprisingly, we found that the increased pairing affinity of 2'-F
      RNA relative to RNA is not, as commonly assumed, the result of a favorable
      entropic contribution ('conformational preorganization'), but instead primarily
      based on enthalpy. Crystal structures at high resolution and osmotic stress
      demonstrate that the 2'-F-RNA duplex is less hydrated than the RNA duplex. The
      enthalpy-driven, higher stability of the former hints at the possibility that the
      2'-substituent, in addition to its important function in sculpting RNA
      conformation, plays an underappreciated role in modulating Watson-Crick base
      pairing strength and potentially pi-pi stacking interactions.

PMID- 21183464
TI  - The translational repressor 4E-BP called to order by eIF4E: new structural
      insights by SAXS.
AB  - eIF4E binding protein (4E-BP) inhibits translation of capped mRNA by binding to
      the initiation factor eIF4E and is known to be mostly or completely unstructured
      in both free and bound states. Using small angle X-ray scattering (SAXS), we
      report here the analysis of 4E-BP structure in solution, which reveals that while
      4E-BP is intrinsically disordered in the free state, it undergoes a dramatic
      compaction in the bound state. Our results demonstrate that 4E-BP and eIF4E form
      a 'fuzzy complex', challenging current visions of eIF4E/4E-BP complex regulation.

PMID- 21183465
TI  - Conjugation polymer nanobelts: a novel fluorescent sensing platform for nucleic
      acid detection.
AB  - In this article, we report on the facile and rapid synthesis of conjugation
      polymer poly(p-phenylenediamine) nanobelts (PNs) via room temperature chemical
      oxidation polymerization of p-phenylenediamine monomers by ammonium persulfate in
      aqueous medium. We further demonstrate the proof-of-concept that PNs can be used
      as an effective fluorescent sensing platform for nucleic acid detection for the
      first time. The general concept used in this approach lies in the facts that the
      adsorption of the fluorescently labeled single-stranded DNA probe by PN leads to
      substantial fluorescence quenching, followed by specific hybridization with the
      complementary region of the target DNA sequence. This results in desorption of
      the hybridized complex from PN surface and subsequent recovery of fluorescence.
      We also show that the sensing platform described herein can be used for
      multiplexing detection of nucleic acid sequences.

PMID- 21183466
TI  - Poly (ADP-ribose) polymerase (PARP) is not involved in base excision repair but
      PARP inhibition traps a single-strand intermediate.
AB  - Base excision repair (BER) represents the most important repair pathway of
      endogenous DNA lesions. Initially, a base damage is recognized, excised and a DNA
      single-strand break (SSB) intermediate forms. The SSB is then ligated, a process
      that employs proteins also involved in SSB repair, e.g. XRCC1, Ligase III and
      possibly PARP1. Here, we confirm the role of XRCC1 and PARP in direct SSB repair.
      Interestingly, we uncover a synthetic lethality between XRCC1 deficiency and PARP
      inhibition. We also treated cells with alkylating agent dimethyl sulfate (DMS)
      and monitored the SSB intermediates formed during BER. DMS-induced SSBs were
      quickly repaired in wild-type cells; while a rapid accumulation of SSBs was
      observed in cells where post-incision repair was blocked by a PARP inhibitor or
      by XRCC1 deficiency (EM9 cells). Interestingly, DMS-induced SSBs did not
      accumulate in PARP1 siRNA depleted cells, demonstrating that PARP1 is not
      required for efficient completion of BER. Based on these results we suggest no
      immediate role for PARP1 in BER, but that PARP inhibitors trap PARP on the SSB
      intermediate formed during BER. Unexpectedly, addition of PARP inhibitor 2 h
      after DMS treatment still increased SSB levels indicating ongoing repair even at
      this late time point.

PMID- 21183468
TI  - Prevention and treatment of vitamin D deficiency in Dutch psychogeriatric nursing
      home residents by weekly half-body UVB exposure after showering: a pilot study.
AB  - BACKGROUND: in older people, induction of cutaneous vitamin D production by
      ultraviolet B (UVB) exposure may be preferable to oral supplementation: it cannot
      cause toxic levels, it helps to prevent polypharmacy and, moreover, there are
      indications that UVB exposure has beneficial effects on health and well being by
      mechanisms other than the vitamin D pathway alone. OBJECTIVE: the aim of this
      pilot study is to investigate whether weekly, half-body, UVB irradiation after
      showering can increase serum 25-hydroxyvitamin D (25(OH)D) to sufficient levels,
      in a Dutch psychogeriatric nursing home population. METHOD: subjects were eight
      psychogeriatric nursing home patients, mean age: 79 +/- 8. Exclusion criteria
      were going outdoors into the sun more than once a week, the presence of actinic
      or cancer skin lesions and known resistance to body contact. The intervention
      consisted of weekly half-body UVB irradiation, after showering, over 8 weeks,
      with 0.5 minimal erythemal dose (MED). Main outcome measures were change in
      fasting serum levels of 25(OH)D and parathyroid hormone (PTH) at 0, 2, 4 and 8
      weeks. RESULTS: at baseline, mean serum 25(OH)D was 28.5 nmol/l. Mean serum
      25(OH)D levels increased to 46.5 nmol/l. Median serum PTH levels decreased by 20%
      after 8 weeks of treatment. CONCLUSION: an 8 week course of weekly, frontal half
      body irradiation with UVB, at 0.5 MED, leads to an significant increase in
      25(OH)D serum levels, but this period is too short to reach vitamin D
      sufficiency.

PMID- 21183467
TI  - Structure-based prediction of RNA-binding domains and RNA-binding sites and
      application to structural genomics targets.
AB  - Mechanistic understanding of many key cellular processes often involves
      identification of RNA binding proteins (RBPs) and RNA binding sites in two
      separate steps. Here, they are predicted simultaneously by structural alignment
      to known protein-RNA complex structures followed by binding assessment with a
      DFIRE-based statistical energy function. This method achieves 98% accuracy and
      91% precision for predicting RBPs and 93% accuracy and 78% precision for
      predicting RNA-binding amino-acid residues for a large benchmark of 212 RNA
      binding and 6761 non-RNA binding domains (leave-one-out cross-validation).
      Additional tests revealed that the method makes no false positive prediction from
      311 DNA binding domains but correctly detects six domains binding with both DNA
      and RNA. In addition, it correctly identified 31 of 75 unbound RNA-binding
      domains with 92% accuracy and 65% precision for predicted binding residues and
      achieved 86% success rate in its application to SCOP RNA binding domain
      superfamily (Structural Classification Of Proteins). It further predicts 25
      targets as RBPs in 2076 structural genomics targets: 20 of 25 predicted ones
      (80%) are putatively RNA binding. The superior performance over existing methods
      indicates the importance of dividing structures into domains, using a Z-score to
      measure relative structural similarity, and a statistical energy function to
      measure protein-RNA binding affinity.

PMID- 21183469
TI  - Here comes the sun: good news for bone health!

PMID- 21183470
TI  - From unemployment to disability? Relationship between unemployment rate and new
      disability pensions in Iceland 1992-2007.
AB  - BACKGROUND: The study was carried out in order to examine the effect of
      unemployment on the incidence of disability pension in Iceland by examining
      changes in this relationship from 1992 to 2007. METHODS: The annual incidence of
      disability pension for the period 1992-2007 was calculated. Correlations and
      significance tests for the relationship between unemployment rates and disability
      pension incidence rates were calculated. The relationship was examined for
      different disease groups. RESULTS: Two big fluctuations occurred in the
      unemployment rate during the study period with an upswing in unemployment from
      1993 to 1995 and in 2002 and 2003. In both cases, there were corresponding
      increases in the incidence of disability pension. The incidence of disability
      pension declined again when the level of unemployment went down, even though not
      to the same extent. CONCLUSIONS: Health and mental and physical capability
      determine the overall incidence of disability pension, but marginal fluctuations
      over time seem to be related to environmental conditions in the labour market,
      especially the unemployment rate. The observed disability pension incidence
      pattern in the two unemployment cycles of the study period indicates mainly that
      people with impaired health are forced out of the labour market in times of
      increasing unemployment rather than pointing towards a negative effect of
      unemployment on health. Our findings indicate that there is a need to strengthen
      the vocational rehabilitation system in Iceland as well as the support system for
      employment and social participation.

PMID- 21183471
TI  - Yearly incidence of mental disorders in economically inactive young adults.
AB  - Increasing rates of mental health problems in youth and an extended period of
      school-to-work transition is a major concern in Sweden and many other European
      countries. In this study, being out of the workforce and not in education was
      associated with severe mental disorders. The risk of being admitted in hospital
      due to depression was more than doubled in economically inactive young adults.
      Similarly, the risk of being admitted to hospital due to self-harm and alcohol
      related disorder was tripled. Drug abuse was seven times more prevalent among
      inactive young adults. Processes leading to economic inactivity and to
      deteriorating mental health are inextricably intertwined. Even if it is not
      possible to clarify if the association is caused by selection or if it is being
      outside of labour force that causes mental disorders, it is still urgent to
      prevent young persons from ending up in long-term economic inactivity.

PMID- 21183472
TI  - The burden of 2009 pandemic influenza A(H1N1) in the Netherlands.
AB  - BACKGROUND: The disease burden of the 2009 influenza pandemic has been debated
      but reliable estimates are lacking. To guide future policy and control, these
      estimates are necessary. This study uses burden of disease measurements to assess
      the contribution of the pandemic influenza A(H1N1) virus to the overall burden of
      disease in the Netherlands. METHODS: The burden of disease caused by 2009
      pandemic influenza was estimated by calculating Disability Adjusted Life Years
      (DALY), a composite measure that combines incidence, sequelae and mortality
      associated with a disease, taking duration and severity into account. Available
      influenza surveillance data sources (primary care sentinel surveillance,
      notification data on hospitalizations and deaths and death registries) were used.
      Besides a baseline scenario, five alternative scenarios were used to assess
      effects of changing values of input parameters. RESULTS: The baseline scenario
      showed a loss of 5800 DALY for the Netherlands (35 DALY per 100 000 population).
      This corresponds to 0.13% of the estimated annual disease burden in the
      Netherlands and is comparable to the estimated disease burden of seasonal
      influenza, despite a different age distribution in incidence and mortality of the
      pandemic compared to seasonal influenza. CONCLUSIONS: This disease burden
      estimate confirmed that, although there was a higher mortality observed among
      young people, the 2009 pandemic was overall a mild influenza epidemic. The
      disease burden of this pandemic was comparable to the burden of seasonal
      influenza in the Netherlands.

PMID- 21183473
TI  - Boc modifies the holoprosencephaly spectrum of Cdo mutant mice.
AB  - Holoprosencephaly (HPE) is caused by a failure to form the midline of the
      forebrain and/or midface. It is one of the most common human birth defects, but
      clinical expression is extremely variable. HPE is associated with mutations in
      the sonic hedgehog (SHH) pathway. Mice lacking the Shh pathway regulator Cdo
      (also called Cdon) display HPE with strain-dependent penetrance and expressivity,
      implicating silent modifier genes as one cause of the variability. However, the
      identities of potential HPE modifiers of this type are unknown. We report here
      that whereas mice lacking the Cdo paralog Boc do not have HPE, Cdo;Boc double
      mutants on a largely Cdo-resistant genetic background have lobar HPE with strong
      craniofacial anomalies and defects in Shh target gene expression in the
      developing forebrain. Boc is therefore a silent HPE modifier gene in mice.
      Furthermore, Cdo and Boc have specific, selective roles in Shh signaling in
      mammals, because Cdo;Boc double-mutant mice do not display the most severe HPE
      phenotype seen in Shh-null mice, nor do they have major defects in digit
      patterning or development of vertebrae, which are also Shh-dependent processes.
      This is in contrast to reported observations in Drosophila, where genetic removal
      of the Cdo and Boc orthologs Ihog and Boi results in a complete loss of response
      to the hedgehog ligand. Therefore, there is evolutionary divergence between
      mammals and insects in the requirement of the hedgehog pathway for Cdo/Ihog
      family members, with mammalian development involving additional factors and/or
      distinct mechanisms at this level of pathway regulation.

PMID- 21183474
TI  - Transient receptor potential ion channel Trpm7 regulates exocrine pancreatic
      epithelial proliferation by Mg2+-sensitive Socs3a signaling in development and
      cancer.
AB  - Genetic analysis of pancreatic development has provided new insights into the
      mechanisms underlying the formation of exocrine pancreatic neoplasia. Zebrafish
      sweetbread (swd) mutants develop hypoplastic acini and dysmorphic ducts in the
      exocrine pancreas, with impeded progression of cell division cycle and of
      epithelial growth. Positional cloning and allelic complementation have revealed
      that the swd mutations affect the transient receptor potential melastatin
      subfamily member 7 (trpm7) gene, which encodes a divalent cation-permeable
      channel with kinase activity. Supplementary Mg(2+) partially rescued the exocrine
      pancreatic defects of the trpm7 mutants by improving cell-cycle progression and
      growth and repressing the suppressor of cytokine signaling 3a (socs3a) gene. The
      role of Socs3a in Trpm7-mediated signaling is supported by the findings that
      socs3a mRNA level is elevated in the trpm7 mutants, and antisense inhibition of
      socs3a expression improved their exocrine pancreatic growth. TRPM7 is generally
      overexpressed in human pancreatic adenocarcinoma. TRPM7-deficient cells are
      impaired in proliferation and arrested in the G0-G1 phases of the cell division
      cycle. Supplementary Mg(2+) rescued the proliferative defect of the TRPM7
      deficient cells. Results of this study indicate that Trpm7 regulates exocrine
      pancreatic development via the Mg(2+)-sensitive Socs3a pathway, and suggest that
      aberrant TRPM7-mediated signaling contributes to pancreatic carcinogenesis.

PMID- 21183476
TI  - Physiological homology between Drosophila melanogaster and vertebrate
      cardiovascular systems.
AB  - The physiology of the Drosophila melanogaster cardiovascular system remains
      poorly characterized compared with its vertebrate counterparts. Basic measures of
      physiological performance remain unknown. It also is unclear whether subtle
      physiological defects observed in the human cardiovascular system can be
      reproduced in D. melanogaster. Here we characterize the cardiovascular physiology
      of D. melanogaster in its pre-pupal stage by using high-speed dye angiography and
      optical coherence tomography. The heart has vigorous pulsatile contractions that
      drive intracardiac, aortic and extracellular-extravascular hemolymph flow.
      Several physiological measures, including weight-adjusted cardiac output, body
      length-adjusted aortic velocities and intracardiac shear forces, are similar to
      those in the closed vertebrate cardiovascular systems, including that of humans.
      Extracellular-extravascular flow in the pre-pupal D. melanogaster circulation
      drives convection-limited fluid transport. To demonstrate homology in heart
      dysfunction, we showed that, at the pre-pupal stage, a troponin I mutant, held
      up2 (hdp2), has impaired systolic and diastolic heart wall velocities. Impaired
      heart wall velocities occur in the context of a non-dilated phenotype with a
      mildly depressed fractional shortening. We additionally derive receiver operating
      characteristic curves showing that heart wall velocity is a potentially powerful
      discriminator of systolic heart dysfunction. Our results demonstrate
      physiological homology and support the use of D. melanogaster as an animal model
      of complex cardiovascular disease.

PMID- 21183477
TI  - Validation of gene regulatory networks: scientific and inferential.
AB  - Gene regulatory network models are a major area of study in systems and
      computational biology and the construction of network models is among the most
      important problems in these disciplines. The critical epistemological issue
      concerns validation. Validity can be approached from two different perspectives
      (i) given a hypothesized network model, its scientific validity relates to the
      ability to make predictions from the model that can be checked against
      experimental observations; and (ii) the validity of a network inference procedure
      must be evaluated relative to its ability to infer a network from sample points
      generated by the network. This article examines both perspectives in the
      framework of a distance function between two networks. It considers some of the
      obstacles to validation and provides examples of both validation paradigms.

PMID- 21183475
TI  - Embryonic frog epidermis: a model for the study of cell-cell interactions in the
      development of mucociliary disease.
AB  - Specialised epithelia such as mucociliary, secretory and transporting epithelia
      line all major organs, including the lung, gut and kidney. Malfunction of these
      epithelia is associated with many human diseases. The frog embryonic epidermis
      possesses mucus-secreting and multiciliated cells, and has served as an excellent
      model system for the biogenesis of cilia. However, ionic regulation is important
      for the function of all specialised epithelia and it is not clear how this is
      achieved in the embryonic frog epidermis. Here, we show that a third cell type
      develops alongside ciliated and mucus-secreting cells in the tadpole skin. These
      cells express high levels of ion channels and transporters; therefore, we suggest
      that they are analogous to ionocytes found in transporting epithelia such as the
      mammalian kidney. We show that frog ionocytes express the transcription factor
      foxi1e, which is required for the development of these cells. Depletion of
      ionocytes by foxi1e knockdown has detrimental effects on the development of
      multiciliated cells, which show fewer and aberrantly beating cilia. These results
      reveal a newly identified role for ionocytes and suggest that the frog embryonic
      skin is a model system that is particularly suited to studying the interactions
      of different cell types in mucociliary, as well as in secretory and transporting,
      epithelia.

PMID- 21183478
TI  - Literature-aided interpretation of gene expression data with the weighted global
      test.
AB  - Most methods for the interpretation of gene expression profiling experiments rely
      on the categorization of genes, as provided by the Gene Ontology (GO) and pathway
      databases. Due to the manual curation process, such databases are never up-to
      date and tend to be limited in focus and coverage. Automated literature mining
      tools provide an attractive, alternative approach. We review how they can be
      employed for the interpretation of gene expression profiling experiments. We
      illustrate that their comprehensive scope aids the interpretation of data from
      domains poorly covered by GO or alternative databases, and allows for the linking
      of gene expression with diseases, drugs, tissues and other types of concepts. A
      framework for proper statistical evaluation of the associations between gene
      expression values and literature concepts was lacking and is now implemented in a
      weighted extension of global test. The weights are the literature association
      scores and reflect the importance of a gene for the concept of interest. In a
      direct comparison with classical GO-based gene sets, we show that use of
      literature-based associations results in the identification of much more specific
      GO categories. We demonstrate the possibilities for linking of gene expression
      data to patient survival in breast cancer and the action and metabolism of drugs.
      Coupling with online literature mining tools ensures transparency and allows
      further study of the identified associations. Literature mining tools are
      therefore powerful additions to the toolbox for the interpretation of high
      throughput genomics data.

PMID- 21183480
TI  - Vascular homeostasis: insights from a fibrotic mouse.

PMID- 21183481
TI  - Understanding gene-environment interactions in a mouse model of Crohn's disease.

PMID- 21183482
TI  - At the leading edge of cancer research: an interview with Joan Brugge. Interview
      by Sarah Allan.

PMID- 21183485
TI  - Adenosine triphosphate-binding cassette transporters mediate chemokine (C-C
      motif) ligand 2 secretion from reactive astrocytes: relevance to multiple
      sclerosis pathogenesis.
AB  - Adenosine triphosphate-binding cassette efflux transporters are highly expressed
      at the blood-brain barrier and actively hinder passage of harmful compounds,
      thereby maintaining brain homoeostasis. Since, adenosine triphosphate-binding
      cassette transporters drive cellular exclusion of potential neurotoxic compounds
      or inflammatory molecules, alterations in their expression and function at the
      blood-brain barrier may contribute to the pathogenesis of neuroinflammatory
      disorders, such as multiple sclerosis. Therefore, we investigated the expression
      pattern of different adenosine triphosphate-binding cassette efflux transporters,
      including P-glycoprotein, multidrug resistance-associated proteins-1 and -2 and
      breast cancer resistance protein in various well-characterized human multiple
      sclerosis lesions. Cerebrovascular expression of P-glycoprotein was decreased in
      both active and chronic inactive multiple sclerosis lesions. Interestingly, foamy
      macrophages in active multiple sclerosis lesions showed enhanced expression of
      multidrug resistance-associated protein-1 and breast cancer resistance protein,
      which coincided with their increased function of cultured foamy macrophages.
      Strikingly, reactive astrocytes display an increased expression of P-glycoprotein
      and multidrug resistance-associated protein-1 in both active and inactive
      multiple sclerosis lesions, which correlated with their enhanced in vitro
      activity on astrocytes derived from multiple sclerosis lesions. To investigate
      whether adenosine triphosphate-binding cassette transporters on reactive
      astrocytes can contribute to the inflammatory process, primary cultures of
      reactive human astrocytes were generated through activation of Toll-like receptor
      3 to mimic the astrocytic phenotype as observed in multiple sclerosis lesions.
      Notably, blocking adenosine triphosphate-binding cassette transporter activity on
      reactive astrocytes inhibited immune cell migration across a blood-brain barrier
      model in vitro, which was due to the reduction of astrocytic release of the
      chemokine (C-C motif) ligand 2. Our data point towards a novel
      (patho)physiological role for adenosine triphosphate-binding cassette
      transporters, suggesting that limiting their activity by dampening astrocyte
      activation may open therapeutic avenues to diminish tissue damage during multiple
      sclerosis pathogenesis.

PMID- 21183483
TI  - Drosophila melanogaster as a model for human intestinal infection and pathology.
AB  - Recent findings concerning Drosophila melanogaster intestinal pathology suggest
      that this model is well suited for the study of intestinal stem cell physiology
      during aging, stress and infection. Despite the physiological divergence between
      vertebrates and insects, the modeling of human intestinal diseases is possible in
      Drosophila because of the high degree of conservation between Drosophila and
      mammals with respect to the signaling pathways that control intestinal
      development, regeneration and disease. Furthermore, the genetic amenability of
      Drosophila makes it an advantageous model species. The well-studied intestinal
      stem cell lineage, as well as the tools available for its manipulation in vivo,
      provide a promising framework that can be used to elucidate many aspects of human
      intestinal pathology. In this Perspective, we discuss recent advances in the
      study of Drosophila intestinal infection and pathology, and briefly review the
      parallels and differences between human and Drosophila intestinal regeneration
      and disease.

PMID- 21183486
TI  - Inhibition of phosphodiesterases rescues striatal long-term depression and
      reduces levodopa-induced dyskinesia.
AB  - The aim of the present study was to evaluate the role of the nitric oxide/cyclic
      guanosine monophosphate pathway in corticostriatal long-term depression induction
      in a model of levodopa-induced dyskinesia in experimental parkinsonism. Moreover,
      we have also analysed the possibility of targeting striatal phosphodiesterases to
      reduce levodopa-induced dyskinesia. To study synaptic plasticity in sham-operated
      rats and in 6-hydroxydopamine lesioned animals chronically treated with
      therapeutic doses of levodopa, recordings from striatal spiny neurons were taken
      using either intracellular recordings with sharp electrodes or whole-cell patch
      clamp techniques. Behavioural analysis of levodopa-induced abnormal involuntary
      movements was performed before and after the treatment with two different
      inhibitors of phosphodiesterases, zaprinast and UK-343664. Levodopa-induced
      dyskinesia was associated with the loss of long-term depression expression at
      glutamatergic striatal synapses onto spiny neurons. Both zaprinast and UK-343664
      were able to rescue the induction of this form of synaptic plasticity via a
      mechanism requiring the modulation of intracellular cyclic guanosine
      monophosphate levels. This effect on synaptic plasticity was paralleled by a
      significant reduction of abnormal movements following intrastriatal injection of
      phosphodiesterase inhibitors. Our findings suggest that drugs selectively
      targeting phosphodiesterases can ameliorate levodopa-induced dyskinesia, possibly
      by restoring physiological synaptic plasticity in the striatum. Future studies
      exploring the possible therapeutic effects of phosphodiesterase inhibitors in non
      human primate models of Parkinson's disease and the involvement of striatal
      synaptic plasticity in these effects remain necessary to validate this
      hypothesis.

PMID- 21183487
TI  - Gamma oscillations in the hippocampus require high complex I gene expression and
      strong functional performance of mitochondria.
AB  - Fast neuronal network oscillations in the gamma range (~30-90 Hz) have been
      implicated in complex brain functions such as sensory processing, memory
      formation and, perhaps, consciousness, and appear to be exceptionally vulnerable
      to various pathologies. However, both energy demand and mitochondrial performance
      underlying gamma oscillations are unknown. We investigated the fundamental
      relationship between acetylcholine-induced gamma oscillations, mitochondrial gene
      expression and oxidative metabolism in hippocampal slice preparations of mouse
      and rat by applying electrophysiology, in situ hybridization, quantitative
      polymerase chain reaction, oxygen sensor microelectrode (interstitial partial
      oxygen pressure) and imaging of mitochondrial redox state [nicotinamide adenine
      dinucleotide (phosphate) and flavin adenine dinucleotide fluorescence]. We show
      that (i) gamma oscillation power, oxygen consumption and expression of complex I
      (nicotinamide adenine dinucleotide:ubiquinone oxidoreductase) subunits are higher
      in hippocampal subfield CA3 than in CA1 and dentate gyrus; (ii) the amount of
      oxygen consumption of gamma oscillations reaches that of seizure-like events;
      (iii) gamma oscillations are exquisitely sensitive to pharmacological complex I
      inhibition; and (iv) gamma oscillations utilize mitochondrial oxidative capacity
      near limit. These data suggest that gamma oscillations are especially energy
      demanding and require both high complex I expression and strong functional
      performance of mitochondria. Our study helps to explain the exceptional
      vulnerability of complex brain functions in ischaemia as well as in
      neurodegenerative and psychiatric disorders that are associated with
      mitochondrial dysfunction.

PMID- 21183488
TI  - Science to practice: versatile method to track transplanted encapsulated islet
      cells with multiple imaging modalities.
AB  - Pancreatic islet transplantation may provide an effective therapy for patients
      with type I diabetes. By encapsulating islets in alginate capsules, their
      survival is substantially improved. Methods to monitor the distribution of the
      encapsulated islets during delivery and afterward would help to optimize this
      type of therapy. Barnett and coworkers (1) showed, for the first time, it is
      possible to visualize encapsulated islets by using magnetic resonance (MR)
      imaging, computed tomography (CT), and ultrasonography (US) after the inclusion
      of perfluorocarbon in the capsules. Importantly, it was shown that the
      therapeutic effect of the islets was sustained for more than 50 days when
      implanted into mice.

PMID- 21183489
TI  - Aneurysmal subarachnoid hemorrhage: DSA versus CT angiography--is the answer
      available?

PMID- 21183490
TI  - The invisible radiologist.

PMID- 21183491
TI  - Functional imaging of the pelvic floor.
AB  - The clinical treatment of patients with anorectal and pelvic floor dysfunction is
      often difficult. Dynamic cystocolpoproctography (DCP) has evolved from a method
      of evaluating the anorectum for functional disorders to its current status as a
      functional method of evaluating the global pelvic floor for defecatory disorders
      and pelvic organ prolapse. It has both high observer accuracy and a high yield of
      positive diagnoses. Clinicians find it a useful diagnostic tool that can alter
      management decisions from surgical to medical and vice versa in many cases.
      Functional radiography provides the maximum stress to the pelvic floor, resulting
      in levator ani relaxation accompanied by rectal emptying-which is needed to
      diagnose defecatory disorders. It also provides organ-specific quantificative
      information about female pelvic organ prolapse-information that usually can only
      be inferred by means of physical examination. The application of functional
      radiography to the assessment of defecatory disorders and pelvic organ prolapse
      has highlighted the limitations of physical examination. It has become clear that
      pelvic floor disorders rarely occur in isolation and that global pelvic floor
      assessment is necessary. Despite the advances in other imaging methods, DCP has
      remained a practical, cost-effective procedure for the evaluation of anorectal
      and pelvic floor dysfunction. In this article, the authors describe the technique
      they use when performing DCP, define the radiographic criteria used for
      diagnosis, and discuss the limitations and clinical utility of DCP.

PMID- 21183492
TI  - CT findings of chemotherapy-induced toxicity: what radiologists need to know
      about the clinical and radiologic manifestations of chemotherapy toxicity.
AB  - Cancer chemotherapy has evolved from cytotoxic agents and now includes several
      new agents that target specific molecules responsible for the regulation of cell
      growth, nutrient supply, and differentiation. These molecularly targeted
      therapies have a different mechanism of action than do classic cytotoxic agents,
      which predominantly attack rapidly proliferating cells. Not surprisingly,
      therefore, the toxicity of targeted and cytotoxic agents may differ in both
      clinical and radiologic presentation. Many of the toxicities of targeted
      therapies are not cumulative or dose dependent, some are asymptomatic, and others
      may first manifest radiologically. It is imperative that radiologists be aware of
      these toxicities and that they learn to recognize the relevant findings so that
      they can provide a complete differential diagnosis and thus play an important
      role in patient care.

PMID- 21183494
TI  - Case 165: Oncogenic osteomalacia.

PMID- 21183495
TI  - Comment on peripherally inserted central catheters in the critical care unit.

PMID- 21183496
TI  - The epidemiology of DSM-IV alcohol use disorders amongst young adults in the
      Australian population.
AB  - AIM: The aim of the study was to examine the descriptive epidemiology of 12-month
      alcohol use disorders (AUDs) amongst young adults in the Australian general
      population. METHODS: The 2007 National Survey of Mental Health and Well Being, a
      nationally representative household survey of 8841 Australian adults (16-85
      years), assessed participants for symptoms of the most prevalent DSM-IV mental
      disorders. Young adults were over-sampled to provide detailed information on this
      age group. RESULTS: 11.1% of young adults in the Australian population were
      diagnosed with an AUD. Compared with the rest of the young adult sample, young
      adults with AUDs were at greater risk of reporting another drug use disorder, an
      anxiety disorder, high levels of consumption, a medium or high score on the
      Kessler Psychological Distress Scale, and a moderate to severe score on the WHO
      Disability Assessment Schedule 2.0. Mental health services were rarely used by
      young adults with AUDs. Difficulties in differentiating young adults diagnosed
      with abuse and those diagnosed with dependence with the criteria we used
      supported accumulating evidence questioning the validity of the abuse-dependence
      distinction. CONCLUSIONS: AUDs in young adulthood are prevalent and associated
      with comorbid psychopathology, risky levels of alcohol consumption and
      disability. Despite the clinical significance of AUDs in this age group, few
      young adults with these disorders use mental health services. In this age group,
      the proposed changes for DSM-V regarding the classification of AUD would seem
      helpful.

PMID- 21183497
TI  - Literature curation of protein interactions: measuring agreement across major
      public databases.
AB  - Literature curation of protein interaction data faces a number of challenges.
      Although curators increasingly adhere to standard data representations, the data
      that various databases actually record from the same published information may
      differ significantly. Some of the reasons underlying these differences are well
      known, but their global impact on the interactions collectively curated by major
      public databases has not been evaluated. Here we quantify the agreement between
      curated interactions from 15 471 publications shared across nine major public
      databases. Results show that on average, two databases fully agree on 42% of the
      interactions and 62% of the proteins curated from the same publication.
      Furthermore, a sizable fraction of the measured differences can be attributed to
      divergent assignments of organism or splice isoforms, different organism focus
      and alternative representations of multi-protein complexes. Our findings
      highlight the impact of divergent curation policies across databases, and should
      be relevant to both curators and data consumers interested in analyzing protein
      interaction data generated by the scientific community. Database URL:
      http://wodaklab.org/iRefWeb.

PMID- 21183498
TI  - Prospectively ECG-triggered 256-slice computed tomography findings in a patient
      with dextrocardia, stent-treated coarctation, and infracardial right-sided
      pulmonary vein deviation.

PMID- 21183499
TI  - Routine early coronary angioplasty after thrombolysis in acute ST-elevation
      myocardial infarction: lysis is not the final step.

PMID- 21183500
TI  - Assessment of multiple cardiac biomarkers in non-ST-segment elevation acute
      coronary syndromes: observations from the MERLIN-TIMI 36 trial.
AB  - AIMS: The aim of this study is to simultaneously evaluate the incremental
      prognostic value of multiple cardiac biomarkers reflecting different underlying
      pathophysiological processes in a well-characterized population of patients with
      non-ST-segment acute coronary syndrome (NSTE-ACS). METHODS AND RESULTS: We
      measured cardiac troponin I (cTnI), N-terminal pro B-type natriuretic peptide (NT
      proBNP), C-reactive protein, and myeloperodixase (MPO) among 4352 patients with
      NSTE-ACS in the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less
      Ischaemia in Non-ST Elevation Acute Coronary-Thrombolysis In Myocardial
      Infarction 36) trial and followed them for a mean of 343 days. When added
      individually to a multivariable model adjusted for clinical characteristics, the
      risk of cardiovascular (CV) death rose in a stepwise fashion with increasing
      quartiles of each biomarker, and when using their pre-defined cut-points [HR(adj)
      2.71 (P < 0.001) for cTnI >=0.03 ng/mL; HR(adj) 3.01 (P < 0.001) for NT-proBNP
      >=400 pg/mL; HR(adj) 1.45 (P = 0.019) for high-sensitivity (hs) C-reactive
      protein >=15 mg/L; and HR(adj) 1.49 (P = 0.006) for MPO >=670 pmol/L]. After
      including all biomarkers, only NT-proBNP and cTnI were independently associated
      with CV death, and only cTnI with myocardial infarction (MI). The addition of NT
      proBNP to a model adjusted for TIMI risk score incorporating cTnI significantly
      improved both the discrimination and re-classification of the model for CV death
      and heart failure (HF) while there was no such improvement after the addition of
      either MPO or hs-C-reactive protein. CONCLUSION: In this study of over 4300
      patients presenting with NSTEACS, we found that both cTnI and NT-proBNP offer
      prognostic information beyond that achieved with clinical risk variables for CV
      death, MI, and HF. Myeloperoxidase and hs-C-reactive protein, while independently
      associated with some adverse CV outcomes, did not provide substantial incremental
      prognostic information when evaluated together with cTnI and NT-proBNP.

PMID- 21183501
TI  - Mesenchymal stem cells improve murine acute coxsackievirus B3-induced
      myocarditis.
AB  - AIMS: Coxsackievirus B3 (CVB3)-induced myocarditis, initially considered a sole
      immune-mediated disease, also results from a direct CVB3-mediated injury of the
      cardiomyocytes. Mesenchymal stem cells (MSCs) have, besides immunomodulatory,
      also anti-apoptotic features. In view of clinical translation, we first analysed
      whether MSCs can be infected by CVB3. Next, we explored whether and how MSCs
      could reduce the direct CVB3-mediated cardiomyocyte injury and viral progeny
      release, in vitro, in the absence of immune cells. Finally, we investigated
      whether MSC application could improve murine acute CVB3-induced myocarditis.
      METHODS AND RESULTS: Phase contrast pictures and MTS viability assay demonstrated
      that MSCs did not suffer from CVB3 infection 4-12-24-48 h after CVB3 infection.
      Coxsackievirus B3 RNA copy number decreased in this time frame, suggesting that
      no CVB3 replication took place. Co-culture of MSCs with CVB3-infected HL-1
      cardiomyocytes resulted in a reduction of CVB3-induced HL-1 apoptosis, oxidative
      stress, intracellular viral particle production, and viral progeny release in a
      nitric oxide (NO)-dependent manner. Moreover, MSCs required priming via
      interferon-gamma (IFN-gamma) to exert their protective effects. In vivo, MSC
      application improved the contractility and relaxation parameters in CVB3-induced
      myocarditis, which was paralleled with a reduction in cardiac apoptosis,
      cardiomyocyte damage, left ventricular tumour necrosis factor-alpha mRNA
      expression, and cardiac mononuclear cell activation. Mesenchymal stem cells
      reduced the CVB3-induced CD4- and CD8- T cell activation in an NO-dependent way
      and required IFN-gamma priming. CONCLUSION: We conclude that MSCs improve murine
      acute CVB3-induced myocarditis via their anti-apoptotic and immunomodulatory
      properties, which occur in an NO-dependent manner and require priming via IFN
      gamma.

PMID- 21183503
TI  - Inflammatory responses of tissue-engineered xenografts in a clinical scenario.
AB  - Acellular tissue-engineered (ATE) xenografts and homografts are used in clinical
      cardiovascular surgery. The present study examined the specific role of
      carbohydrate antigen (alpha-Gal and T-antigen) in immune response after
      decellularisation in tissue-engineered xenografts (porcine pulmonary artery and
      bovine jugular vein). An enzyme-linked immunosorbent assay (ELISA) was used to
      ascertain whether implantation of bioprostheses, ATE xenografts and mechanical
      valve replacement result in augmentation of anti-alpha-Gal IgM antibodies within
      eight days of surgery (each group, n=6). Kinetics of host inflammatory response
      on surgically explanted ATE xenografts was also studied. Immunostaining for alpha
      Gal and T-antigen detected the presence of them in the native tissue but they
      were absent in processed ATE xenografts from the same tissue. A significant
      increase in the concentration of anti-alpha-Gal IgM antibodies was observed in
      the serum of bioprosthetic valve recipients as compared to ATE xenograft
      recipients (P<0.05). Organised collagen, and decreased inflammatory response with
      increase in endothelisation and vascularisation was evident beyond one year of
      surgery as compared to early periods in ATE xenografts. This study demonstrates
      that decellularisation of xenografts and further processing of these tissues
      enabled reduction of inflammatory stimulus with autologous recellularisation with
      no calcification.

PMID- 21183504
TI  - Massive calcification of the tricuspid valve papillary muscles in right
      ventricular endomyocardial fibrosis.
AB  - Right-sided forms account for one-fourth of endomyocardial fibrosis cases in
      central Africa. A 50-year-old female patient with endo- myocardial fibrosis
      presented with unusual calcifications of the right ventricular endocardium that
      embedded the tricuspid valve papillary muscles. Bioprosthetic tricuspid valve
      replacement together with right ventricular endocardectomy was performed with a
      good clinical outcome.

PMID- 21183505
TI  - Candidemia after cardiac surgery in the intensive care unit: an observational
      study.
AB  - Candidemia is a well-recognized complication of hospital stay, especially in
      critically ill patients. There is not a general consensus that predictors for
      candidemia in cardiosurgical intensive care unit (cICU) are different from a
      general ICU and it has been reported that cardiopulmonary bypass time is a
      specific risk factor in the cICU. We performed a prospective study to evaluate
      the main predictors for candidemia in patients admitted to the cICU. Included
      patients were adults admitted between July 2005 and December 2007 with an ICU
      length of stay (ICU-LOS) >=48 hours after cardiac surgery. Exclusion criteria
      were solid organ or bone marrow transplants, previous diagnosis of candidemia or
      other invasive infections and ICU stay before surgery. A multiple regression
      analysis was performed to identify the risk factors. Among 1955 patients admitted
      to the cICU, 345 were enrolled. Only 26 patients (1.3%) had candidemia after an
      ICU-LOS of 20 days (inter-quartile range, IQR 8-49 days). Total parenteral
      nutrition [odds ratio (OR)=9.56; confidence interval (CI)=1.741-52.534], severe
      sepsis (OR=4.20; CI=1.292-13.667), simplified acute physiology score II (OR=1.16;
      CI=1.052-1.278) and ICU-LOS >20 days (OR=6.38; CI=1.971-20.660) were independent
      predictors of candidemia. Patients undergoing cardiac surgery developed
      candidemia late after cICU admission and the independent predictors were similar
      to the general ICU.

PMID- 21183506
TI  - Lipomatosis of interventricular septum and both ventricles: an extremely rare
      pattern.
AB  - Fatty masses of the heart are relatively uncommon. This report is about an
      extremely rare case of cardiac lipomatosis that implicates both ventricles and
      inter-atrial septum. The patient was a 27-year-old female who was accidentally
      diagnosed during a routine physical examination. Trans-thoracic echocardiography
      (TTE) discovered a large homogenous bi-lobed, non-encapsulated echogenic mass.
      Magnetic resonance imaging (MRI) showed soft tissue abnormal enhancement in the
      anterior left base of the heart and sub-aortic outflow tract. A trans-jugular
      echomyocardial biopsy was done because of a lack of a definite diagnosis by non
      invasive techniques. Pathological study showed benign fatty infiltration
      suggestive for benign lipomatous hypertrophy.

PMID- 21183507
TI  - Suppression of endothelin-1-induced cardiac myocyte hypertrophy by PPAR agonists:
      role of diacylglycerol kinase zeta.
AB  - AIMS: Ligand activation of peroxisome proliferator-activated receptors (PPARs)
      prevents cardiomyocyte hypertrophy, but the underlying signalling mechanisms
      remain unknown. We previously reported that the anti-hypertrophic effect of the
      dietary polyunsaturated fatty acid, conjugated linoleic acid (CLA), was
      associated with the upregulation of diacylglycerol (DAG) kinase (DGK). DGK
      catalyses phosphorylative conversion/attenuation of DAG, thereby modulating
      protein kinase C (PKC) and G-protein signalling. As the anti-hypertrophic effects
      of CLA were attenuated by inhibitors of PPARs, the present aim was to investigate
      the involvement of DGK in the anti-hypertrophic actions of bona fide selective
      PPAR agonists. METHODS AND RESULTS: Endothelin-1 (ET1)-induced hypertrophy of
      neonatal, and then adult, Sprague-Dawley rat cardiomyocytes served as
      experimental paradigms. Expression of DGKzeta, the predominant DGK isoform in
      myocytes, was stimulated by ligands of PPARgamma (troglitazone) or PPARalpha
      (fenofibrate) and was accompanied by increased DGK activity. Troglitazone or
      fenofibrate prevented hypertrophic indicators elicited by ET1, including myocyte
      size augmentation, de novo protein synthesis, hypertrophic gene expression, and
      activation of the pro-hypertrophic signal, PKCepsilon. shRNA knockdown of DGKzeta
      abolished the growth-inhibitory effects of PPARs and restored all ET1-induced
      aspects of hypertrophy. Importantly, the involvement of DGK in the ability of
      troglitazone and fenofibrate to block ET1-induced hypertrophy and PKCepsilon
      signalling was verified in adult rat myocytes. CONCLUSION: Collectively, these
      findings show that the anti-hypertrophic actions of PPARs require DGKzeta. Thus,
      within the cardiomyocyte, there exists a PPAR-DGK signalling axis that underpins
      the ability of PPAR ligands to inhibit ET1-dependent hypertrophy.

PMID- 21183508
TI  - Review focus on inorganic nitrite and nitrate in cardiovascular health and
      disease.

PMID- 21183509
TI  - Arterial injury promotes medial chondrogenesis in Sm22 knockout mice.
AB  - AIMS: Expression of SM22 (also known as SM22alpha and transgelin), a vascular
      smooth muscle cells (VSMCs) marker, is down-regulated in arterial diseases
      involving medial osteochondrogenesis. We investigated the effect of SM22
      deficiency in a mouse artery injury model to determine the role of SM22 in
      arterial chondrogenesis. METHODS AND RESULTS: Sm22 knockout (Sm22(-/-)) mice
      developed prominent medial chondrogenesis 2 weeks after carotid denudation as
      evidenced by the enhanced expression of chondrogenic markers including type II
      collagen, aggrecan, osteopontin, bone morphogenetic protein 2, and SRY-box
      containing gene 9 (SOX9). This was concomitant with suppression of VSMC key
      transcription factor myocardin and of VSMC markers such as SM alpha-actin and
      myosin heavy chain. The conversion tendency from myogenesis to chondrogenesis was
      also observed in primary Sm22(-/-) VSMCs and in a VSMC line after Sm22 knockdown:
      SM22 deficiency altered VSMC morphology with compromised stress fibre formation
      and increased actin dynamics. Meanwhile, the expression level of Sox9 mRNA was up
      regulated while the mRNA levels of myocardin and VSMC markers were down
      regulated, indicating a pro-chondrogenic transcriptional switch in SM22-deficient
      VSMCs. Furthermore, the increased expression of SOX9 was mediated by enhanced
      reactive oxygen species production and nuclear factor-kappaB pathway activation.
      CONCLUSION: These findings suggest that disruption of SM22 alters the actin
      cytoskeleton and promotes chondrogenic conversion of VSMCs.

PMID- 21183510
TI  - APO010, a synthetic hexameric CD95 ligand, induces human glioma cell death in
      vitro and in vivo.
AB  - Death receptor targeting has emerged as one of the promising novel approaches of
      cancer therapy. The activation of one such prototypic death receptor, CD95
      (Fas/APO-1), has remained controversial because CD95 agonistic molecules have
      exhibited either too strong toxicity or too little activity. The natural CD95
      ligand (CD95L) is a cytokine, which needs to trimerize to mediate a cell death
      signal. Mega-Fas-Ligand, now referred to as APO010, is a synthetic hexameric CD95
      agonist that exhibits strong antitumor activity in various tumor models. Here, we
      studied the effects of APO010 in human glioma models in vitro and in vivo.
      Compared with a cross-linked soluble CD95L or a CD95-agonistic antibody, APO010
      exhibited superior activity in glioma cell lines expressing CD95 and triggered
      caspase-dependent cell death. APO010 reduced glioma cell viability in synergy
      when combined with temozolomide. The locoregional administration of APO010
      induced glioma cell death in vivo and prolonged the survival of tumor-bearing
      mice. A further exploration of APO010 as a novel antiglioma agent is warranted.

PMID- 21183511
TI  - Descemet's membrane automated endothelial keratoplasty (DMAEK): visual outcomes
      and visual quality.
AB  - BACKGROUND/AIMS: To determine whether the stromal rim that carries the bare
      endothelial graft in Descemet's membrane automated endothelial keratoplasty
      (DMAEK) has any effect on final visual outcome or visual quality. METHODS: Twenty
      four DMAEK eyes and 22 Descemet's membrane endothelial keratoplasty (DMEK) eyes
      (with no stromal rim) were evaluated for corrected distance acuity, full-field
      Humphrey visual field (VF) 120-2 and pupil size. The inner and outer diameter of
      the DMAEK stromal ring was measured from slit lamp photos. Patients completed a
      questionnaire rating postoperative symptoms and visual complaints. Exclusion
      criteria were pre-existing glaucoma, retinal pathology or inability to return for
      postoperative examinations. RESULTS: Median Snellen acuities were comparable
      between DMAEK and DMEK groups: 20/25 and 20/20-3, respectively. The mean central
      opening of the DMAEK stromal ring was 5.6 * 5.5 (range 3.8-6.9) mm. The incidence
      of VF defects, visual complaints of glare, halos, light sensitivity and night
      driving difficulties was comparable between groups (all p > 0.1). A larger
      scotopic pupil size (< 5.5 mm) was not associated with increased incidence of VF
      defects in either group (p = 0.3). CONCLUSIONS: Surprisingly, compared with
      uniformly thin DMEK grafts, DMAEK grafts with a stromal rim had no increase in VF
      defects or visual complaints.

PMID- 21183512
TI  - Preferential hyperacuity perimeter in assessing responsiveness to ranibizumab
      therapy for exudative age-related macular degeneration.
AB  - AIM: To investigate the ability of the preferential hyperacuity perimeter test to
      assess responsiveness to ranibizumab therapy for exudative age-related macular
      degeneration (AMD). METHODS: Fourteen consecutive patients with newly diagnosed
      choroidal neovascularisation underwent a preferential hyperacuity perimeter
      metamorphopsia test (main outcome measures) 1 h before (baseline) and 1 h, 1 day,
      1 week and 1 month after one intravitreal injection of ranibizumab (0.05 ml/0.5
      mg). Best corrected visual acuity (BCVA) and several spectral domain optical
      coherence tomography (OCT) parameters (secondary outcome measures) were compared
      with the metamorphopsia test. RESULTS: Fourteen eyes (14 patients, 78% women,
      mean age 83 +/- 6.2 years) were included in the analysis. The mean preferential
      hyperacuity perimeter metamorphopsia test score improved significantly from 20.4
      +/- 35 at baseline to 9.2 +/- 23 after the single ranibizumab injection (p <
      0.05). The mean reduction in central macular thickness, maximal retinal thickness
      at the fovea, maximal height of subretinal fluid, maximal diameter of the largest
      retinal cyst and maximal height of pigment epithelial detachment, as evaluated by
      spectral domain OCT, closely reflected the functional improvements as evaluated
      by preferential hyperacuity perimeter, showing a significant correlation with
      metamorphopsia changes (Spearman correlation 0.9, p < 0.05). Mean BCVA improved
      significantly from 20/80 to 20/60 (p < 0.05). A significant correlation was also
      found between the mean BCVA changes and the mean metamorphopsia changes (Spearman
      correlation 0.97, p < 0.05). The correlation coefficient between OCT measurements
      and preferential hyperacuity perimeter score within subjects was 0.51 (p < 0.05).
      CONCLUSION: The improvement in metamorphopsia test score after intravitreal
      ranibizumab injection, which correlated closely with improvement in several OCT
      parameters, suggests that the preferential hyperacuity perimeter test may be used
      to monitor the response to anti-vascular endothelial growth factor (VEGF)
      treatment in patients with exudative AMD.

PMID- 21183513
TI  - Novel anterior-chamber angle measurements by high-definition optical coherence
      tomography using the Schwalbe line as the landmark.
AB  - OBJECTIVE: To propose the Schwalbe line (SL) as a new anatomical landmark,
      independent of the scleral spur (SS) location, for assessing anterior chamber
      angle (ACA) width quantitatively with high-definition optical coherence
      tomography (HD-OCT). METHODS: Study subjects underwent dark-room gonioscopy and
      HD-OCT in one randomly selected eye. The authors developed a computer-aided
      program to define two new quantitative parameters for assessing ACA width:
      Schwalbe line-angle opening distance (SL-AOD) measured at the SL, and Schwalbe
      line-trabecular-iris space area (SL-TISA) measured 500 MUm from the SL. The
      associations between SL parameters, SS parameters and gonioscopic grading were
      evaluated. RESULTS: Seventy-three (47 females, 26 males) subjects were recruited,
      the majority of whom were Chinese (89%). The authors excluded 29 images (19.9%)
      owing to poor image quality, leaving 117 HD-OCT images (65 nasal, 52 temporal)
      for analysis. SL and SS could be identified in 95% and 85% of quadrants
      respectively (p = 0.035). SL-AOD and SL-TISA were significantly correlated with
      SS parameters (all r >= 0.85) and gonioscopic grading (all r >= 0.69). In eyes
      with closed angles (n = 36), SL parameters showed strong correlations with
      gonioscopic grading (r ranged from 0.43 to 0.44). Conclusions Novel angle
      parameters, based on SL as a landmark, may be useful to quantify ACA width and to
      assess for risk of angle closure.

PMID- 21183514
TI  - Decreased ocular inflammatory attacks and background retinal and disc vascular
      leakage in patients with Behcet's disease on infliximab therapy.
AB  - AIM: To evaluate the efficacy of infliximab treatment in patients with refractory
      uveoretinitis associated with Behcet's disease. METHODS: Clinical records of 14
      patients were retrospectively reviewed. Patients received infliximab infusions (5
      mg/kg) at weeks 0, 2 and 6, and every 8 weeks thereafter. The main outcome
      measures were frequency of clinically observable ocular inflammatory attacks,
      background retinal and disc vascular leakage as assessed by fluorescein
      angiography during periods of clinical quiescence, visual acuity and adverse
      effects. RESULTS: The median follow-up after initiating infliximab therapy was 19
      months (range 12-29 months). At 12 months, eight of 14 patients (57%) had
      experienced no inflammatory attacks, and the frequency of attacks was
      significantly reduced when compared with the 6-month period just prior to
      infliximab use. Background retinal and disc vascular leakage assessed at 12
      months improved in 11 of 14 patients (79%). Visual acuity improved or remained
      unchanged at 12 months in 26 of 28 eyes (93%). Infliximab therapy was terminated
      in two patients owing to infusion reactions. However, no serious adverse effects
      were observed. CONCLUSION: Infliximab over the first year of treatment appeared
      effective in reducing ocular inflammatory attacks, as well as background retinal
      and disc vascular leakage, in patients with refractory uveoretinitis associated
      with Behcet's disease.

PMID- 21183515
TI  - Composite grafts in eyelid reconstruction: the complications and outcomes.
AB  - AIMS: To describe the outcomes and complications for composite eyelid grafts in a
      large case series over a 9-year period. METHOD: A retrospective study of all
      patients who underwent a composite graft for eyelid reconstruction between
      January 2000 and May 2009. A composite eyelid graft involves the excision of a
      full thickness pentagonal wedge from the donor eyelid, which is inserted into the
      recipient eyelid defect. The orbicularis muscle is discarded from the composite
      graft. Initial diagnosis, complications, postoperative eyelid contour and colour
      were recorded. RESULTS: Forty-two patients were identified in the study period;
      the mean age was 69 years. Reconstruction following basal cell carcinoma excision
      was the commonest indication for surgery. Thirty-five composite grafts were
      performed for lower eyelid defects and seven for upper lid defects. The average
      size of the grafts was 9.1 (range 7-12) mm. Five patients required two grafts to
      reconstruct the defect. Thirty-six (86%) patients achieved a satisfactory contour
      and 33 (78%) patients had good matching skin colour. Partial dehiscence occurred
      in five patients and three patients had bulkiness of the graft postoperatively.
      We had no episodes of graft failure, although two patients had skin necrosis,
      which resolved. CONCLUSION: Composite eyelid grafts when combined with
      mobilisation of the recipient orbicularis muscle can result in good preservation
      of eyelid function with satisfactory cosmesis.

PMID- 21183516
TI  - Transretinal degeneration in ageing human retina: a multiphoton microscopy
      analysis.
AB  - AIM: Retinal cell remodelling has been reported as a consistent feature of
      ageing. However, the degree to which this results in transretinal degeneration is
      unclear. To address this, the authors used multiphoton microscopy to quantify
      retinal degeneration in post-mortem human eyes of two age groups. METHODS:
      Retinas from six young subjects (18-33 years old) and six older subjects (74-90
      years old) were prepared as wholemount preparations. All retinas were stained
      with 4,6-diamidino-2-phenylindole and imaged by multiphoton confocal microscopy
      to quantify neuron densities in the retinal ganglion cell layer (RGCL), inner
      nuclear layer (INL) and outer nuclear layer (ONL). Neurons were counted using
      automated cell identification algorithms. All retinas were imaged hydrated to
      minimise tissue artefacts. RESULTS: In both groups, 56% of the area within the
      central 4 mm eccentricity and 27% of the area with eccentricity between 4 mm and
      7 mm were imaged. Compared with young subjects, the peak RGCL neuron loss in the
      aged subjects (25.5%) was at 1 mm eccentricity. INL and ONL neuron densities
      significantly decreased at 1-2 mm eccentricity (8.7%) and 0.5-4 mm eccentricity
      (15.6%) respectively (P <0.05). The reduction in neuron density in the INL
      corresponded, spatially, to the region with the greatest neuron loss in the RGCL
      and ONL. CONCLUSIONS: This is the first study to correlate neurodegeneration in
      different populations of cells in the ageing retinas. These data confirm that the
      greatest neuronal loss occurs in the RGCL and ONL in human ageing retinas,
      whereas the INL is relatively preserved.

PMID- 21183517
TI  - Role of chemotherapy and molecularly targeted agents in the treatment of adenoid
      cystic carcinoma of the lacrimal gland.
AB  - Adenoid cystic carcinoma (ACC) is the most common malignant epithelial cancer of
      the lacrimal gland. Despite a slow rate of growth, ACCs are ultimately associated
      with poor clinical outcome. Given the rarity of this disease, most
      recommendations regarding therapy are guided by expert opinion and retrospective
      data rather than level 1 evidence. Surgery and postoperative radiation therapy
      are commonly used as initial local treatment. In patients at high risk of
      recurrence, concomitant platinum-based chemotherapy may be added to postoperative
      radiotherapy in an attempt to enhance radio-sensitivity. While encouraging
      responses have been reported with intra-arterial neoadjuvant chemotherapy, this
      strategy is associated with substantial toxicity and should be considered
      investigational. For patients with metastatic disease not amenable to surgery or
      radiotherapy, chemotherapy may have a role based on its modest efficacy in non
      lacrimal ACC. Similarly, molecular targeted agents may have a role, although the
      agents tested to date in non-lacrimal ACC have been disappointing. A better
      understanding of the biology of ACC will be crucial to the future success of
      developing targeted agents for this disease.

PMID- 21183518
TI  - Analgesic effect of supplemental intracameral lidocaine during
      phacoemulsification under topical anaesthesia: a randomised controlled trial.
AB  - AIMS: To determine the analgesic effect of supplemental intracameral lidocaine 1%
      during phacoemulsification under topical anaesthesia, and to assess the risk
      factors associated with pain. METHODS: In a double-masked, randomised, clinical
      trial, 506 patients undergoing phacoemulsification under topical anaesthesia were
      randomised to receive a supplemental intracameral injection of either 0.5 cc of
      1% lidocaine (277 patients, 54.7%) or balanced salt solution (BSS) (229 patients,
      45.3%). Patients were interviewed by a trained interviewer using a standardised
      questionnaire. The main outcome measure was intraoperative pain, scored on a
      visual analogue scale of 0-10. Logistic regression was performed to assess ORs.
      RESULTS: 125 of 277 patients (45.1%) experienced pain in the lidocaine group,
      compared with 123 of 229 patients (53.7%) in the BSS group. The proportion of
      patients who experienced pain was significantly lower in the intracameral
      lidocaine group compared with the BSS group (multivariate OR 0.68, 95% CI 0.47 to
      0.97; p=0.034). The median pain score (range) was 0.0 for intracameral lidocaine
      group compared with 1.0 for BSS group (p=0.039). Pain was more common in females
      (54.3% vs 43.6%; OR 1.56), non-Chinese (62.3% vs 46.9%; OR 2.13) and those who
      had previous cataract surgery to the fellow eye (55.3% vs 44.7%; OR 1.61).
      CONCLUSION: The use of 0.5 cc of 1% intracameral lidocaine during
      phacoemulsification under topical anaesthesia significantly reduces pain
      experienced by patients. Risk factors for pain include females, non-Chinese and
      previous cataract surgery.

PMID- 21183519
TI  - Clues to duration of undiagnosed disease from retinopathy and maculopathy at
      diagnosis in type 2 diabetes: a cross-sectional study.
AB  - AIMS: To extrapolate, from the proportion of subjects with observable retinopathy
      at diagnosis of type 2 diabetes mellitus in routine clinical practice, the mean
      duration of undiagnosed diabetes. METHODS: On 1 October 1999, there were 4313
      patients with type 2 diabetes in the 41 participating practices in the Tayside
      region (registered with one of 166 GPs). 501 (12%; 95% CI 11 to 13%) patients
      were selected using a pseudo-random number allocation algorithm, and practice
      lists checked for recently deceased, non-residents (45 exclusions). Retinopathy
      was graded by validated slit lamp biomicroscopy and four-field stereo
      photography. Date of first diagnosis of diabetes was ascertained from the
      regional diabetes register created using multiple source data capture. RESULTS:
      Of living Tayside resident patients, 295 from 456 invited type 2 patients (65%)
      were examined. 14.68% (95% CI 12.48 to 16.88%) were found to have retinopathy at
      diagnosis. Assuming a linear model, these data suggest that the onset of
      detectable retinopathy occurs 5.77 years (95% CI 4.6 to 7 years) before
      diagnosis. Comparison using the log rank test with survival to onset of sight
      threatening retinopathy/maculopathy in 291 patients with type 1 diabetes mellitus
      also examined from the same population cohort showed the 95% CIs of length of
      preclinical diabetes to be between 3.0 and 9.4 years. CONCLUSION: There is
      accumulating evidence to question the assumption of linearity as a model of
      choice. The authors' understanding of a distinct glycaemic threshold for retinal
      change is also overly simplistic and consequently the bounds of uncertainty
      concerning the preclinical duration of disease are considerable.

PMID- 21183520
TI  - Use of chaperones for intimate examinations in the emergency department.

PMID- 21183521
TI  - Comparison between intubation through ILMA and Airtraq, in different non
      conventional patient positions: a manikin study.
AB  - BACKGROUND: Tracheal intubation is often difficult in the prehospital setting,
      especially in trapped casualties, when long extrication time is anticipated and
      conventional laryngoscopy cannot be achieved. The aim of the present study was
      the comparison of applicability and efficacy of two alternative techniques:
      intubation using a laryngeal mask airway (ILMA) or an Airtraq laryngoscope in
      different patient positions, using an airway management manikin. METHODS: 20
      anaesthetists attempted manikin intubations standing behind the manikin (Sup),
      standing in front and facing the manikin's head (Fac), facing the manikin in the
      sitting position (Sit) and facing the manikin lying in the lateral decubitus
      position (Lat), using either Airtraq or ILMA techniques. The intubations were
      evaluated regarding the success rate, number of attempts and time needed for
      successful intubation, teeth damage and overall difficulty. RESULTS: All
      intubation attempts were successful for both techniques. Intubations through ILMA
      were completed with a significantly greater number of attempts and longer time in
      the Lat position, compared to Fac, Sit and Sup (p<0.05), whereas intubations
      using Airtraq in the Sup and Fac positions were completed with a significantly
      greater number of attempts and longer time, compared to Sit and Lat positions
      (p<0.05). Both ILMA and Airtraq can be used for securing the airway when direct
      laryngoscopy is impossible due to patient position. ILMA seems to cause greater
      difficulty in the Lat position, whereas Airtraq intubation is more easily
      performed in the Sit and Lat positions. CONCLUSIONS: These preliminary data in
      manikins could indicate the applicability of the methods to the prehospital
      setting.

PMID- 21183522
TI  - Mephedrone toxicity in a Scottish emergency department.
AB  - OBJECTIVE: To review and improve the evidence base regarding the toxic effects of
      Mephedrone, a cathinone derivative which was first believed to have been
      synthesised and propagated in 2007. On the 7th April 2010 the Misuse of Drugs Act
      1971 (Amendment) Order 2010 was passed, declaring 4-Methylmethcathinone and other
      substituted cathinones Class B drugs as of 16 April 2010. This took place despite
      a perceived lack of evidence as to its potential harms. METHODS: We undertook a
      critical review of the available literature to see what evidence existed for the
      potential effects of mephedrone ingestion. We then conducted our own
      retrospective consecutive case series of all patients presenting to the Aberdeen
      Royal Infirmary Emergency Department from the 1st December until the 16th April
      (the date at which Mephedrone was officially proscripted). The notes were
      examined for amounts, timings, sources and reasons for ingestion. Symptoms,
      biometric, ECG and blood analysis data were also recorded along with management
      and disposal outcomes. RESULTS: 11 articles relating to mephedrone toxicity were
      identified and reviewed. 89 subjects were found for our case series. This
      compared to only 27 patients presenting with ingestion of substances (heroin,
      cocaine, cannabis) at that time illegal. 30 patients stated ingestion of
      mephedrone in isolation and a further 27 patients stated ingestion of mephedrone
      with alcohol in addition. CONCLUSION: A profile of largely psychoactive and
      cardiovascular toxicity is described with drug naivety perhaps explaining the
      high rates of bingeing and addiction reported.

PMID- 21183523
TI  - Therapeutic hypothermia for out-of-hospital cardiac arrest: implementation in a
      district general hospital emergency department.
AB  - BACKGROUND: The use of therapeutic hypothermia is recommended for unconscious
      adult patients with return of spontaneous circulation (ROSC) after out-of
      hospital ventricular fibrillation cardiac arrest. There is evidence that the time
      taken to achieve target temperature impacts survival. OBJECTIVES: To audit the
      performance of an emergency department (ED) in implementing therapeutic
      hypothermia and achieving target temperature in survivors of out-of-hospital
      cardiac arrest admitted to the intensive care unit (ICU). METHODS: Data were
      extracted from the medical records of patients admitted to the ICU from the ED in
      the Royal United Hospital following out-of-hospital cardiac arrest (OHCA) between
      June 2002 and October 2008. The intervals between ROSC and initiation of cooling
      and between initiation of cooling and achieving the core temperature of 34
      degrees C were recorded. RESULTS: During this period, 83 patients were admitted
      to the ICU following OHCA. Of these, 67 (81%) were actively cooled. All 16
      patients who were not cooled had recognised exclusion criteria. The median time
      (IQR) from ROSC to initiation of cooling was 60 (40-165) minutes and the median
      time (IQR) to reach 34 degrees C was 175 (40-420) minutes. Of the 67 who were
      cooled, 44 (66%) achieved the temperature of 34 degrees C within 4 h, the audit
      standard published by the Royal College of Anaesthetists. In 29 (43%) patients,
      the temperature increased after leaving the ED. CONCLUSIONS: Among OHCA patients
      who met recognised inclusion criteria, therapeutic hypothermia was implemented
      successfully by the ED staff. The temperature should be measured continuously
      from the same site in both the ED and the ICU. This will provide consistent and
      continuous temperature monitoring between the ED and the ICU and will enable
      prompt intervention to prevent temperature increases.

PMID- 21183524
TI  - Nurse-initiated defibrillation: are nurses confident enough?
AB  - OBJECTIVES: To determine the capability of nurses to identify ventricular
      fibrillation (VF) and ventricular tachycardia (VT) rhythms on an ECG and carry
      out subsequent defibrillation on their own as soon as they identify and confirm
      cardiac arrest. METHODS: This was a prospective cohort study to determine the
      capability of emergency department (ED) nurses to recognise VF or pulseless VT
      correctly and their willingness to perform defibrillation immediately in an ED of
      a teaching hospital in Hong Kong. A questionnaire was completed before and after
      a teaching session focusing on the identification of rhythms in cardiac arrest
      and defibrillation skills. Correct answers for both ECG interpretation and
      defibrillation decisions scored one point for each question. The differences in
      mean scores between the pre-teaching and post-teaching questionnaires of all
      nurses were calculated. RESULTS: 51 pre-teaching and 43 post-teaching
      questionnaires were collected. There were no statistically significant changes in
      ECG scores after teaching. For defibrillation scores, there was an overall
      improvement in the defibrillation decision (absolute mean difference 0.42,
      p=0.014). Performance was also improved by the teaching (absolute mean difference
      0.465, p=0.046), reflected by the combination of both scores. Two-thirds (67%) of
      nurses became more confident in managing patients with shockable rhythms.
      CONCLUSION: Nurses improve in defibrillation decision-making skills and
      confidence after appropriate brief, focused in-house training.

PMID- 21183525
TI  - UK guidelines for the management of pituitary apoplexy a rare but potentially
      fatal medical emergency.

PMID- 21183526
TI  - Unintentional strangulation by a cervical collar after attempted suicide by
      hanging.
AB  - We report the case of a young man who attempted suicide by hanging and whose
      neurological status deteriorated until the cervical collar, that had been
      correctly placed by the prehospital team, was removed. We discuss the
      physiopathological mechanisms leading to death in hanging that is, a blockage of
      the blood stream to the brain leading to vasogenic and cytotoxic cerebral edema
      rather than asphyxia or spinal fracture. Our case supports the early removal of
      neck stabilization devices that can dangerously harm the patient after an
      attempted suicide by hanging, by increasing intracerebral pressure.

PMID- 21183527
TI  - Access to care among emergency department patients.
AB  - OBJECTIVE: The number of annual patient visits to US emergency departments (ED)
      has been increasing since 1995, whereas the number of ED is decreasing. Previous
      studies have identified many reasons why patients seek care in ED, including lack
      of access to care elsewhere, lack of insurance, inability to see their doctor in
      a timely manner and lower levels of social support. This study identifies factors
      that influence patients' decisions to seek care in ED and assesses their access
      to primary care. METHODS: A prospective study, conducted by standardised verbal
      interview with adult ED patients, was performed in the XXX ED during June-July
      2009. Non-English speaking patients, the mentally incapacitated and those under
      severe distress were excluded. Consenting patients were asked a series of
      questions on access to primary care, factors that influenced their decision to
      attend the ED, health insurance status and demographic information. RESULTS:
      Among 292 study participants (89% response rate), the majority were over 40 years
      (52%), Caucasian (69%) and unemployed (58%). Among employed participants, 66%
      (N=88/133) of employers offered health insurance. Most participants had a primary
      care physician (PCP; 73%; N=214), but a minority had called their PCP about the
      current problem (31%; N=78/253). Most participants came to the ED because of
      convenience/location (41%) or preference for this institution (23%). Participants
      came to the ED, rather than their regular doctor, because they had no PCP (27%),
      an emergency condition (19%), or communication challenges (17%). CONCLUSION:
      Convenience, location, institutional preference and access to other physicians
      are common factors that influence patients' decisions to seek care in ED.

PMID- 21183528
TI  - Regional survey of CTX-M-type extended-spectrum beta-lactamases among
      Enterobacteriaceae reveals marked heterogeneity in the distribution of the ST131
      clone.
AB  - OBJECTIVES: To establish the prevalence and diversity of clinically significant
      extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae harbouring
      bla(CTX-M) in the West Midlands region of the UK. METHODS: During a 2 month
      period, 370 consecutive, non-duplicate isolates were collected from 13
      laboratories. Isolates were screened for the presence of bla(CTX-M) by multiplex
      PCR and genotyped using denaturing HPLC (DHPLC). Clonal relationships were
      studied by PFGE and O25b-ST131 Escherichia coli were identified by PCR. RESULTS:
      Two hundred and ninety-four out of 345 ESBL-producing isolates (85.2%) carried
      bla(CTX-M). CTX-M group 1 enzymes were expressed in 284 (96.6%) isolates, with
      the other 10 carrying group 9, 2 and 25/26 genes. All group 1 isolates had
      bla(CTX-M-15) DHPLC profiles. The bla(CTX-M) E. coli were split into 23 PFGE
      clusters. The largest cluster (RE1) was indistinguishable from the previously
      described strain A and all but one harboured bla(CTX-M-15.) A total of 66% of E.
      coli were O25b-ST131 positive. CONCLUSIONS: The CTX-M-15-producing RE1 clone
      (strain A) is the predominant clone in the West Midlands. This clone has spread
      throughout the region since its emergence in an outbreak 3 years earlier. Most,
      but not all, RE1 isolates belong to the O25b-ST131 lineage, providing further
      evidence that this lineage plays a pivotal role in the clonal dispersal of CTX-M
      15-producing Enterobacteriaceae. Strain A was found to be considerably more
      heterogeneous than when first described and has acquired greater resistance to
      gentamicin. Approximately one-third of CTX-M producers represented a wide variety
      of unrelated strains. The study shows the rapid spread and diversification of CTX
      M-producing Enterobacteriaceae over a 3 year period.

PMID- 21183530
TI  - Accidental renal injury by an external heating device during surgery in rats.
AB  - Hypothermia can be caused by anaesthesia and/or surgery and represents a daily
      challenge in the operating room. Experimental animal surgery settings typically
      use heating pads or warming blankets to maintain the rodent's body temperature
      during long-lasting experiments. Warming is crucial in small animal experiments
      because these animals quickly lose temperature due to their large body surface to
      body weight ratio. While establishing a left ventricular infarction model in
      rats, we inserted a rectal temperature probe. The heating pad's set point was 37
      degrees C. Although a dual set point control circuit should prevent overheating,
      we observed a maximum heating pad's surface temperature of 43 degrees C between
      the animal's back and the surface of the heating pad. At the end of the
      experiments, which lasted up to 8 h, the animals showed severe haematuria and
      segmental kidney damage. We hypothesized that overheating of the heating pad and
      uneven distribution of temperature led to kidney damage. Therefore, the maximal
      temperature of commonly used heating pads must be tightly controlled to avoid
      overheating, which may cause kidney or tissue injury, may falsify the
      experimental data and could influence the study results.

PMID- 21183529
TI  - MicroRNAs: new players in the DNA damage response.
AB  - The DNA damage response (DDR) is a signal transduction pathway that decides the
      cell's fate either to repair DNA damage or to undergo apoptosis if there is too
      much damage. Post-translational modifications modulate the assembly and activity
      of protein complexes during the DDR pathways. MicroRNAs (miRNAs) are emerging as
      a class of endogenous gene modulators that control protein levels, thereby adding
      a new layer of regulation to the DDR. In this review, we describe a new role for
      miRNAs in regulating the cellular response to DNA damage with a focus on DNA
      double-strand break damage. We also discuss the implications of miRNA's role in
      the DDR to stem cells, including embryonic stem cells and cancer stem cells,
      stressing the potential applications for miRNAs to be used as sensitizers for
      cancer radiotherapy and chemotherapy.

PMID- 21183531
TI  - Is prevention a fantasy, or the future of medicine? A panoramic view of recent
      data, status, and direction in cardiovascular prevention.
AB  - Americans are under assault by a fierce epidemic of obesity, diabetes, and
      cardiovascular disease, of their own doing. Lowered death rates from heart
      disease and reduced rates of smoking are seriously threatened by the inexorable
      rise in overweight and obesity. Latest data indicate that 32% of children are
      overweight or obese, and fewer than 17% exercise sufficiently. Over 68% of adults
      are overweight, 35% are obese, nearly 40% fulfill criteria for the metabolic
      syndrome, 8-13% have diabetes, 34% have hypertension, 36% have prehypertension,
      29% have prediabetes, 15% of the population with either diabetes, hypertension,
      or dyslipidemia are undiagnosed, 59% engage in no vigorous activity, and fewer
      than 5% of the US population qualifies for the American Heart Association (AHA)
      definition of ideal cardiovascular health. Health, nutrition, and exercise
      illiteracy is prevalent, while misinformation and unrealistic expectations are
      the norm. Half of American adults have at least one cardiovascular risk factor.
      Up to 65% do not have their conventional risk biomarkers under control. Of those
      patients with multiple risk factors, fewer than 10% have all of them adequately
      controlled. Even when patients are treated according to evidence-based protocols,
      about 70% of cardiac events remain unaddressed. Undertreatment is also common.
      Poor patient adherence, probably well below 50%, adds further difficulty in
      reducing cardiovascular risk. Available data indicate that only a modest fraction
      of the total cardiovascular risk burden in the population is actually now being
      eliminated. A fresh view of these issues, a change in current philosophy, leading
      to new and different, multimechanistic methods of prevention may be needed.
      Adherence to published guidelines will improve substantially outcomes in both
      primary and secondary prevention. Primordial prevention, which does not allow
      risk values to appear in a population, affords more complete protection than
      subsequent partial reversal of elevated risk factors or biomarkers. Current
      evidence supports recent calls for massive educational programs supporting
      primordial prevention, individual responsibility and pride in achieving
      population-wide ideal cardiovascular health through lifestyle modification.
      Environmental and social changes will be necessary, along with major supportive
      adjustments in the food industry and the assistance of the media. Cooperation is
      critical to the success of such an initiative.

PMID- 21183532
TI  - Safety and efficacy of triple antithrombotic therapy after percutaneous coronary
      intervention in patients needing long-term anticoagulation.
AB  - BACKGROUND: Optimal antithrombotic therapy after percutaneous coronary
      intervention (PCI) is currently undefined in patients requiring long-term
      anticoagulation. Previous studies comparing triple therapy (TT) of warfarin,
      aspirin and clopidogrel with standard dual therapy (DT) of aspirin and
      clopidogrel have yielded conflicting results. Meta-analysis of these studies was
      performed to evaluate safety and efficacy of TT. METHODS: A total of 1482
      patients from 6 studies were analyzed using the Mantel-Haenszel random effect
      model to extract incidence of major bleeding. The secondary end point assessed by
      three of these studies was major adverse cardiac events (MACEs: cardiovascular
      death, myocardial infarction and thromboembolic complications). The incidence of
      MACEs was computed using the Mantel-Haenszel fixed effect model. Combined
      relative risks (RRs) across all of the studies and the 95% confidence intervals
      (CIs) were determined. A two-sided alpha error <0.05 was considered statistically
      significant. RESULTS: Baseline characteristics were similar in both groups.
      Compared with patients receiving DT, the risk of major bleeding was significantly
      higher in the TT group (RR: 2.74, CI: 1.08-6.98; p=0.034). However, risk of MACE
      was significantly lower in the TT group (RR: 0.72, CI: 0.56-0.98; p=0.014).
      CONCLUSION: In patients requiring long-term anticoagulation after PCI, TT may be
      superior to DT in reducing the incidence of MACEs, however risk of major bleeding
      complications is increased significantly.

PMID- 21183533
TI  - ST segment elevation secondary to paracetamol overdose.

PMID- 21183534
TI  - Cellular effects of energetic heavy ions: from DNA breaks to chromosomal
      rearrangements.
AB  - Risk from exposure to energetic heavy ions is considered one of the main problems
      for human space exploration. Late stochastic risk estimates, particularly cancer,
      are affected by large uncertainties. Basic cell biology studies to elucidate the
      mechanisms involved in genetic damage are necessary to reduce the uncertainty and
      eventually design effective countermeasures. To study the influence of nuclear
      architecture on the formation of chromosomal rearrangements, normal diploid human
      fibroblasts have been exposed to heavy ions in horizontal and vertical positions.
      Analysis of chromosomal aberrations by arm-specific mFISH shows that, at the same
      radiation dose, the yield of chromosomal damage is modified by the irradiation
      geometry. A clear difference is seen in the fraction of aberrant cells, owing to
      the different nuclear cross sections.

PMID- 21183535
TI  - Analysis of the effect of structural materials in a wall-less tissue-equivalent
      proportional counter irradiated by 290 MeV u(-1) carbon beam.
AB  - Effects of structural materials in a wall-less tissue-equivalent proportional
      counter were evaluated based on the calculation of energy deposits by EGS5 and
      the measurement of lineal energy distributions using 290 MeV u(-1) carbon beams.
      It is found that the correction of measured data based on simulation is necessary
      for understanding the energy deposition spectra in the homogeneous condition in
      tissues.

PMID- 21183536
TI  - A kinetic model of single-strand annealing for the repair of DNA double-strand
      breaks.
AB  - Ionising radiation induces different types of DNA damage, including single-strand
      breaks, double-strand breaks (DSB) and base damages. DSB are considered to be the
      most critical lesion to be repaired. The three main competitive pathways in the
      repair of DSB are non-homologous end joining (NHEJ), homologous recombination
      (HR) and single-strand annealing (SSA). SSA is a non-conservative repair pathway
      requiring direct repeat sequences for the repair process. In this work, a
      biochemical kinetic model is presented to describe the SSA repair pathway. The
      model consists of a system of non-linear ordinary differential equations
      describing the steps in the repair pathway. The reaction rates were estimated by
      comparing the model results with the experimental data for chicken DT40 cells
      exposed to 20 Gy of X-rays. The model successfully predicts the repair of the
      DT40 cells with the reaction rates derived from the 20-Gy X-ray experiment. The
      experimental data and the kinetic model show fast and slow DSB repair components.
      The half time and fractions of the slow and the fast components of the repair
      were compared for the model and the experiments. Mathematical and computational
      modelling in biology has played an important role in predicting biological
      mechanisms and stimulating future experimentation. The present model of SSA adds
      to the modelling of NHEJ and HR to provide a more complete description of DSB
      repair pathways.

PMID- 21183537
TI  - Characterization of the radiation environment by Liulin-type spectrometers.
AB  - Liulin-type spectrometers can characterise the type of predominant particles and
      their energy in the radiation environment. The results from calibrations and
      space and aircraft experiments revealed that the most informative is by the shape
      of the deposited energy spectrum. Spectra generated by galactic cosmic rays (GCR)
      protons and their secondaries look like straight lines in the coordinates
      deposited energy/deposited per channel dose rate. The position of the maximum of
      the deposited energy spectra depends on the incident energy of the incoming
      protons. Spectra generated by relativistic electrons in the outer radiation belt
      have a maximum in the first channels. For higher energy depositions, these
      spectra are similar to the GCR spectra. All types of spectra have a knee close to
      6.3 MeV of deposited energy, which corresponds to the stopping energy of protons
      in the detector.

PMID- 21183538
TI  - Modulation of the activity of the NADPH oxidase system by reactive oxygen
      species: influence of catalase.
AB  - The nicotinamide adenine dinucleotide phosphate oxidase complex (Nox) is a major
      source of non-mitochondrial reactive oxygen species in cells. Nox contains both
      membrane (Cytb(558)) and cytosolic (p40(phox), p47(phox), p67(phox) and Rac)
      components. Nox has been submitted to a combination of oxygen free radicals
      produced by irradiation and to hydrogen peroxide. Irradiation of a single
      component with high doses led to partial inactivation; however, the irradiation
      of the whole system during its assembly phase with lower doses (2-10 Gy) led
      either to activation (2.7 Gy) or to strong inactivation if irradiation took place
      during the first minute of the assembly. Incubation of the membrane fractions or
      of p67(phox) with H(2)O(2) led to fast inactivation. Catalase protected weakly
      p67(phox) from H(2)O(2). Conversely, incubation of the membrane fractions with
      catalase led to over-activation of the system.

PMID- 21183539
TI  - Electron emission from condensed phase material induced by fast protons.
AB  - Monte Carlo track simulation has become an important tool in radiobiology. Monte
      Carlo transport codes commonly rely on elastic and inelastic electron scattering
      cross sections determined using theoretical methods supplemented with gas-phase
      data; experimental condensed phase data are often unavailable or infeasible. The
      largest uncertainties in the theoretical methods exist for low-energy electrons,
      which are important for simulating electron track ends. To test the reliability
      of these codes to deal with low-energy electron transport, yields of low-energy
      secondary electrons ejected from thin foils have been measured following passage
      of fast protons. Fast ions, where interaction cross sections are well known,
      provide the initial spectrum of low-energy electrons that subsequently undergo
      elastic and inelastic scattering in the material before exiting the foil surface
      and being detected. These data, measured as a function of the energy and angle of
      the emerging electrons, can provide tests of the physics of electron transport.
      Initial measurements from amorphous solid water frozen to a copper substrate
      indicated substantial disagreement with MC simulation, although questions
      remained because of target charging. More recent studies, using different
      freezing techniques, do not exhibit charging, but confirm the disagreement seen
      earlier between theory and experiment. One now has additional data on the
      absolute differential electron yields from copper, aluminum and gold, as well as
      for thin films of frozen hydrocarbons. Representative data are presented.

PMID- 21183540
TI  - Extremity and eye lens doses in interventional radiology and cardiology
      procedures: first results of the ORAMED project.
AB  - The main objective of WP1 of the ORAMED (Optimization of RAdiation protection for
      MEDical staff) project is to obtain a set of standardised data on extremity and
      eye lens doses for staff in interventional radiology (IR) and cardiology (IC) and
      to optimise staff protection. A coordinated measurement program in different
      hospitals in Europe will help towards this direction. This study aims at
      analysing the first results of the measurement campaign performed in IR and IC
      procedures in 34 European hospitals. The highest doses were found for pacemakers,
      renal angioplasties and embolisations. Left finger and wrist seem to receive the
      highest extremity doses, while the highest eye lens doses are measured during
      embolisations. Finally, it was concluded that it is difficult to find a general
      correlation between kerma area product and extremity or eye lens doses.

PMID- 21183541
TI  - A study of neutron radiation quality with a tissue-equivalent proportional
      counter for a low-energy accelerator-based in vivo neutron activation facility.
AB  - The accelerator-based in vivo neutron activation facility at McMaster University
      has been used successfully for the measurement of several minor and trace
      elements in human hand bones due to their importance to health. Most of these in
      vivo measurements have been conducted at a proton beam energy (E(p)) of 2.00 MeV
      to optimise the activation of the selected element of interest with an effective
      dose of the same order as that received in chest X rays. However, measurement of
      other elements at the same facility requires beam energies other than 2.00 MeV.
      The range of energy of neutrons produced at these proton beam energies comes
      under the region where tissue-equivalent proportional counters (TEPCs) are known
      to experience difficulty in assessing the quality factor and dose equivalent. In
      this study, the response of TEPCs was investigated to determine the quality
      factor of neutron fields generated via the (7)Li(p, n)(7)Be reaction as a
      function of E(p) in the range 1.884-2.56 MeV at the position of hand irradiation
      in the facility. An interesting trend has been observed in the quality factor
      based on ICRP 60, Q(ICRP60), such that the maximum value was observed at
      E(p)=1.884 MeV (E(n)=33+/-16 keV) and then continued to decline with increasing
      E(p) until achieving a minimum value at E(p)=2.0 MeV despite a continuous
      increase in the mean neutron energy with E(p). This observation is contrary to
      what has been observed with direct fast neutrons where the quality factor was
      found to increase continuously with an increase in E(p) (i.e. increasing E(n)).
      The series of measurements conducted with thermal and fast neutron fields
      demonstrate that the (14)N(n, p)(14)C produced 580 keV protons in the detector
      play an important role in the response of the counter under 2.0 MeV proton energy
      (E(n) <= 250 keV). In contrast to the lower response of TEPCs to low-energy
      neutrons, the quality factor is overestimated in the range 1-2 depending on beam
      energy <2.0 MeV. This study provides an insight to understanding the response of
      TEPCs in low-energy neutron fields where the neutrons are moderated using a
      polyethylene moderator.

PMID- 21183542
TI  - The WST survival assay: an easy and reliable method to screen radiation-sensitive
      individuals.
AB  - An easy, fast and reliable method was developed to screen hundreds of Epstein
      Barr virus-transformed cell lines (lymphoblastoid cell lines, LCLs) for radiation
      sensitivity that were generated from lymphocytes isolated from young lung cancer
      patients. The WST-1 test explores the metabolic activity of the mitochondria as
      an indicator for the vital status of cells. Cell proliferation as well as
      indirect cell death can be quantified by this method on a large scale in
      microtiter plates. Cell survival was measured at 24- and 48-h post-irradiation
      with 10 Gy ((137)Cs source) by the WST-1 assay and Trypan blue staining. To set
      up the experimental screening conditions and to establish a positive and a
      negative control, an ATM-mutated cell line from a radiation-sensitive ATM patient
      and an ATM proficient cell line from a healthy brother were compared. An optimal
      differentiation between the two cell lines was demonstrated for 10 Gy and 24- and
      48-h cell growth after irradiation. Upon screening 120 LCLs of young lung cancer
      patients under these conditions, 5 of them were found to be radiation sensitive
      to a high degree of statistical significance. The results have been confirmed by
      a second laboratory by means of Trypan blue testing. The WST-1 test represents an
      efficient and reliable method by means of screening for radiation-sensitive cell
      lines.

PMID- 21183543
TI  - Dose-response prediction for radiation-induced chromosomal instability.
AB  - Radiation induces chromosome aberrations (CA) that are detected in the first post
      irradiation cell cycle and in descendants of irradiated cells. Unstable
      aberrations in the progeny of exposed cells are referred to as one of the
      hallmarks of chromosomal instability (CIN). One of the important questions is
      what is the relationship between the dose response for radiation-induced CA and
      delayed CA, or CIN. To address this question, a mechanistic model for CIN was
      developed. Delayed CA are assumed to be formed both by transmission from previous
      mitotic cycles owing to chromosome breakage-fusion mechanism and by means of
      generation of DNA/chromosome breakage de novo in each cell cycle of survived
      cells. Monte Carlo simulation of DNA/chromosome breakage, CA production, cell
      death due to unstable CA and cell cycle kinetics was performed to predict the
      dose response for CIN. Different shapes of CIN dose-response curves were
      predicted for various time points after irradiation and under several assumptions
      on delayed DNA/chromosome breakage generation. For one of the scenarios studied,
      the pronounced dose dependence at early time points flattened or even turned into
      dose independence in a wide dose range after many rounds of replication where a
      stationary state between CA generation and elimination was achieved. This dose
      independence was shown to be in concert with the experimental data.

PMID- 21183544
TI  - Chromosome aberration induction is dependent on the spatial distribution of
      energy deposition through a cell nucleus.
AB  - The importance of the spatial distribution of energy deposition through the
      nucleus in determining the resultant chromosome rearrangements was investigated
      using fluorescent in situ hybridisation technique following either uniform or
      partial irradiation of HF19 human fibroblast cells with low-LET 1.5 keV ultrasoft
      X-rays. Irradiations were performed with and without a copper irradiation mask
      with a Poisson distribution of micron-sized holes immediately below the
      irradiation dish and the results are compared with previous results obtained
      following exposure to a Poisson distribution of alpha particles. For the same
      radiation quality, the spatial distribution of energy deposition within the
      nucleus was found to be important in determining the ultimate biological
      response, with an increased ratio of complex-to-simple aberrations observed for
      partial compared to uniform irradiation. Comparisons between low-LET ultrasoft X
      rays and high-LET alpha particles indicate that the sub-micron clustering of
      damage along the alpha particle track is more important than just the total
      number of double-strand breaks produced.

PMID- 21183545
TI  - Proton inactivation of melanoma cells enhanced by fotemustine.
AB  - Response of human HTB140 melanoma cells to proton irradiation in combination with
      fotemustine (FM) was investigated. Effects of these agents were analysed on cell
      proliferation and induction of apoptosis. Cells pretreated with 100- or 250-uM of
      FM were irradiated in the middle of the therapeutic 62-MeV proton spread-out
      Bragg peak, with a dose of 16 Gy. All treatments reduced proliferation and
      survival of melanoma cells. The most pronounced effects of the combined treatment
      were obtained for cell survivals. The level of apoptosis increased after all
      applied treatments. Particularly good pro-apoptotic effect was achieved when
      proton irradiation was combined with 250 MUM of FM. This was followed by the
      increased expression of p53 gene. The obtained results have shown that combined
      application of FM and protons significantly reduced growth of this resistant
      melanoma cell line.

PMID- 21183546
TI  - Simulation of phoswich detectors using MCNPX and EGSNRC.
AB  - The in vivo monitoring Lab at KIT uses two phoswich detectors for routine lung
      counting. A simplified model of one of them has been implemented in the two Monte
      Carlo codes EGSnrc and MCNPX. The active part of the detector consists of a
      crystal of NaI(Tl) and one of CsI(Tl): the energy deposited in both the crystals
      have been studied to consider the effect of the anticoincidence logic, present in
      the read-out electronics of the detectors and not yet studied with Monte Carlo
      simulations. Only the NaI(Tl) crystal has then been used to study the escape
      peaks at several energies, which are more prominent at low energies. The results
      from the two codes have been compared. The comparison of the codes predictions
      for the escape peaks has been then extended using the model of a germanium
      detector.

PMID- 21183547
TI  - The thermoluminescence efficiency of Li2B4O7:Cu and of CaSO4:Tm for photons.
AB  - The intrinsic thermoluminescence (TL) efficiency of a TL detector relates the
      absorbed dose in the detector material to the light yield observed upon
      evaluation. Knowledge of the TL efficiency is of interest when performing
      numerical simulations of detector response, where only absorbed dose can be
      predicted. Here, the experimental determination of TL efficiency for calcium
      sulphate (CaSO(4):Tm) and lithium borate (Li(2)B(4)O(7):Cu) is reported. These
      materials are widely used in Panasonic dosemeter badges. The results of the study
      are in agreement with predictions from track structure theory and microdosimetry,
      relating an enhanced light yield at low X-ray energies to supralinear behaviour
      of the TL phosphor.

PMID- 21183548
TI  - H2AX phosphorylation in response to DNA double-strand break formation during
      bystander signalling: effect of microRNA knockdown.
AB  - Upon DNA double-strand break (DSB) formation, hundreds of H2AX molecules in the
      chromatin flanking the break site are phosphorylated on serine residue 139,
      termed gamma-H2AX, so that virtually every DSB site in a nucleus can be
      visualised within 10 min of its formation using an antibody to gamma-H2AX. One
      application of this sensitive assay is to examine the induction of DNA double
      strand damage in subtle non-targeted cellular effects such as the bystander
      effect. Here whether microRNA (miRNA) serve as a primary signalling mechanism for
      bystander effect propagation by comparing matched human colon carcinoma cell
      lines with wild-type or depleted levels of mature miRNAs was investigated. No
      major differences were found in the levels of induced gamma-H2AX foci in the
      tested cell lines, indicating that though miRNAs play a role in bystander effect
      manifestation, they appear not to be the primary bystander signalling molecules
      in the formation of bystander effect-induced DSBs.

PMID- 21183549
TI  - Dose levels of the occupational radiation exposures in Poland based on results
      from the accredited dosimetry service at the IFJ PAN, Krakow.
AB  - Individual dosimetry service based on thermoluminescence (TLD) detectors has
      started its activity at the Institute of Nuclear Physics (IFJ) in Krakow in 1965.
      In 2002, the new Laboratory of Individual and Environment Dosimetry (Polish
      acronym LADIS) was established and underwent the accreditation according to the
      EN-PN-ISO/IEC 17025 standard. Nowadays, the service is based on the worldwide
      known standard thermoluminescent detectors MTS-N (LiF:Mg,Ti) and MCP-N
      (LiF:Mg,Cu,P), developed at IFJ, processed in automatic thermoluminescent DOSACUS
      or RE2000 (Rados Oy, Finland) readers. Laboratory provides individual monitoring
      in terms of personal dose equivalent H(p)(10) and H(p)(0.07) in photon and
      neutron fields, over the range from 0.1 mSv to 1 Sv, and environmental dosimetry
      in terms of air kerma K(a) over the range from 30 MUGy to 1 Gy and also ambient
      dose equivalent H*(10) over the range from 30 MUSv to 1 Sv. Dosimetric service is
      currently performed for ca. 3200 institutions from Poland and abroad, monitored
      on quarterly and monthly basis. The goal of this paper is to identify the main
      activities leading to the highest radiation exposures in Poland. The paper
      presents the results of statistical evaluation of ~ 100,000 quarterly H(p)(10)
      and K(a) measurements performed between 2002 and 2009. Sixty-five per cent up to
      90 % of all individual doses in Poland are on the level of natural radiation
      background. The dose levels between 0.1 and 5 mSv per quarter are the most
      frequent in nuclear medicine, veterinary and industrial radiography sectors.

PMID- 21183550
TI  - Review of retrospective dosimetry techniques for external ionising radiation
      exposures.
AB  - The current focus on networking and mutual assistance in the management of
      radiation accidents or incidents has demonstrated the importance of a joined-up
      approach in physical and biological dosimetry. To this end, the European
      Radiation Dosimetry Working Group 10 on 'Retrospective Dosimetry' has been set up
      by individuals from a wide range of disciplines across Europe. Here, established
      and emerging dosimetry methods are reviewed, which can be used immediately and
      retrospectively following external ionising radiation exposure. Endpoints and
      assays include dicentrics, translocations, premature chromosome condensation,
      micronuclei, somatic mutations, gene expression, electron paramagnetic resonance,
      thermoluminescence, optically stimulated luminescence, neutron activation,
      haematology, protein biomarkers and analytical dose reconstruction. Individual
      characteristics of these techniques, their limitations and potential for further
      development are reviewed, and their usefulness in specific exposure scenarios is
      discussed. Whilst no single technique fulfils the criteria of an ideal dosemeter,
      an integrated approach using multiple techniques tailored to the exposure
      scenario can cover most requirements.

PMID- 21183551
TI  - Radiation protection for accompanying person and radiation workers in PET/CT.
AB  - The purposes of the present study are to measure the total radiation doses for
      the radiation workers and for the accompanying person to the patients in positron
      emission tomography (PET)/computed tomography (CT) imaging. Urines samples from
      the patients were collected at 43, 62, 87, 117, 238, 362 min after the 555-MBq
      (18)flour-fluorodeoxyglucose ((18)F-FDG) injection and activities were measured.
      Dose rates were recorded using a Geiger-Muller counter and the total radiation
      doses were measured with using an electronic personnel dosemeter. According to
      the results here, 18.4 % of (18)F-FDG was excreted in the urine in 117 min after
      injection. At 117th min after injection, dose rates were determined as 345, 220,
      140, 50 and 15 uSv h(-1), at proposed distances. The radiation doses after 117
      min were measured as 3.92 mSv at 0.1 m, 2.11 mSv at 0.25 m and 1.08 mSv at 0.5 m.
      In conclusion, radiation protection will be sufficient within 2 h after (18)F-FDG
      injection for PET/CT imaging in daily practice.

PMID- 21183552
TI  - Real-time measurement of individual occupational radon exposures in tombs of the
      Valley of the Kings, Egypt.
AB  - The active radon exposure meter developed recently at the German Research Center
      for Environmental Health (Helmholtz Zentrum Munchen) was used to measure radon
      concentrations in 12 tombs located in the Valley of the Kings, Egypt. Radon
      concentrations in air between 50 +/- 7 and 12 100 +/- 600 Bq m(-3) were obtained.
      The device was also used to measure individual radon exposures of those persons
      working as safeguards inside the tombs. For a measurement time of 2-3 d, typical
      individual radon exposures ranged from 1800 +/- 400 to 240 000 +/- 13 000 Bq h m(
      3), depending on the duration of measurement and radon concentration in the
      different tombs. Based on current ICRP dose conversion conventions for workers
      and on equilibrium factors published in the literature for these tombs,
      individual effective dose rates that range from 1.5 +/- 0.3 to 860 +/- 50 uSv d(
      1) were estimated. If it is assumed that the climatic conditions present at the
      measurement campaign persist for about half a year, in this area, then effective
      doses up to ~ 66 mSv could be estimated for half a year, for some of the
      safeguards of tombs where F-values were known. To reduce the exposure of the
      safeguards, some recommendations are proposed.

PMID- 21183553
TI  - Assessing adrenal status in patients before and immediately after coronary artery
      bypass graft surgery.
AB  - OBJECTIVE: Patients with cortisol deficiency poorly tolerate any systemic
      inflammatory response syndrome (SIRS), and may die if not treated with sufficient
      exogenous glucocorticoids. Controversy surrounds what constitutes a 'normal'
      adrenal response in critical illness. This study uses conventional tests for
      adrenal insufficiency to investigate cortisol status in patients undergoing
      elective coronary artery bypass surgery, a condition frequently associated with
      SIRS. DESIGN: A prospective, observational study. METHODS: Thirty patients with
      impaired left ventricular function (ejection fraction >23% <50%) underwent basal
      ACTH measurement, and a short cosyntropin test (250 MUg, i.v.) 1 week
      preoperatively, and at +4 h following induction of general anaesthesia.
      Preoperatively, a 30 min cortisol level post cosyntropin >550 nmol/l was taken as
      a normal response. RESULTS: Prior to surgery, all patients had a normal response
      to cosyntropin. Postoperatively, eight patients (26.7%) did not achieve
      stimulated cortisol levels >550 nmol/l and the mean peak cortisol postoperatively
      was lower (1048 vs 730 nmol/l; P<0.001). There was a significant rise in ACTH
      after surgery (21 vs 184 ng/l; P=0.007) and reduction in Delta-cortisol post
      cosyntropin (579 vs 229 nmol/l; P<0.001). There was no change in basal cortisol
      pre- and post-operatively (447 vs 501; P=0.4). All patients underwent routine,
      uneventful postoperative recovery. CONCLUSION: Up to one quarter of patients with
      a normal cortisol status preoperatively demonstrated a raised ACTH and deficient
      cortisol response postoperatively. Despite these responses, all patients had
      uneventful outcomes. These data reinforce the need for caution when interpreting
      results of endocrine testing following major surgery or in the intensive care
      environment, and that prognostic value of these results may be of limited use.

PMID- 21183554
TI  - Polymorphisms at the regulatory regions of the CASR gene influence stone risk in
      primary hyperparathyroidism.
AB  - BACKGROUND AND OBJECTIVE: Single nucleotide polymorphisms (SNPs) of the calcium
      sensing receptor (CASR) gene at the regulatory region were associated with
      idiopathic calcium nephrolithiasis. To confirm their association with
      nephrolithiasis, we tested patients with primary hyperparathyroidism (PHPT).
      DESIGN: A genotype-phenotype association study. METHODS: In all, 332 PHPT
      patients and 453 healthy controls were genotyped for the rs7652589 (G>A) and
      rs1501899 (G>A) SNPs sited in the noncoding regulatory region of the CASR gene.
      Allele, haplotype, and diplotype distribution were compared between PHPT patients
      and controls, and in stone forming and stone-free PHPT patients. RESULTS: The
      allele frequency at rs7652589 and rs1501899 SNPs was similar in PHPT patients and
      controls. The A minor alleles at these two SNPs were more frequent in stone
      forming (n=157) than in stone-free (n=175) PHPT patients (rs7652589: 36.9 vs
      27.1%, P=0.007; rs1501899: 37.1 vs 26.4%, P=0.003). Accordingly, homozygous or
      heterozygous PHPT patients for the AA haplotype (n=174, AA/AA or AA/GG diplotype)
      had an increased stone risk (odds ratio 1.83, 95% confidence interval 1.2-2.9,
      P=0.008). Furthermore, these PHPT patients had higher serum concentrations of
      ionized calcium and parathyroid hormone (1.50 +/- 0.015 mmol/l and 183 +/- 12.2
      pg/ml) than patients with the GG/GG diplotype (n=145, 1.47 +/- 0.011 mmol/l
      (P=0.04) and 150 +/- 11.4 pg/ml (P=0.049)). Using a logistic regression model,
      the increase in stone risk in PHPT patients was predicted by AA/AA or AA/GG
      diplotype, the highest tertile of serum ionized calcium values and the lowest
      tertile of age. CONCLUSIONS: Polymorphisms located in the regulatory region of
      the CASR gene may increase susceptibility of the PHPT patients to kidney stone
      production.

PMID- 21183555
TI  - Sheehan's syndrome in modern times: a nationwide retrospective study in Iceland.
AB  - BACKGROUND AND OBJECTIVE: Half a century ago the prevalence of Sheehan's syndrome
      (SS) was 10-20 per 100,000 women. With better obstetric help the prevalence is
      assumed to have decreased, especially in developed countries. The aim of this
      study is to estimate the prevalence of SS in modern times in Iceland. DESIGN: We
      studied the prevalence of SS in 2009 in a nationwide retrospective population
      based study. METHODS: All patients with diagnosed SS were identified, and
      information regarding obstetric care, clinical presentation and hormonal assays
      was collected. Correlation was calculated with Kendall's tau-b. Significance
      level: P<0.05. RESULTS: Eight women were identified with SS; thus, the prevalence
      of SS in 2009 was 5.1 per 100,000 women. The mean age at delivery and diagnosis
      was 33.0 and 36.6 respectively, resulting in a diagnostic delay (DD) of 1-240
      months. Four women had low blood pressure during delivery, and five had massive
      blood loss (>1000 ml). Six had complicated deliveries. The most common clinical
      presentation was failure to lactate and failure to resume menstruation. The
      patients had three to five failing pituitary axis. There was no correlation
      between bleeding at delivery or the number of hormonal axes affected and DD.
      CONCLUSION: The prevalence of SS in Iceland was higher than we expected in a
      country with modern obstetric care. Long DD and incidental diagnosis indicate
      that women might be lacking correct diagnosis and treatment, and thus the
      prevalence of SS is even higher. As SS is easily diagnosed and treatable, but can
      be life-threatening if unrecognised, doctors need to be aware of the disease.

PMID- 21183556
TI  - Sampling and mass spectrometric analytical methods for five antineoplastic drugs
      in the healthcare environment.
AB  - CONTEXT: Healthcare worker exposure to antineoplastic drugs continues to be
      reported despite safe handling guidelines published by several groups. Sensitive
      sampling and analytical methods are needed so that occupational safety and health
      professionals may accurately assess environmental and biological exposure to
      these drugs in the workplace. OBJECTIVE: To develop liquid chromatography-mass
      spectrometry/mass spectrometry (LC-MS/MS) analytical methods for measuring five
      antineoplastic drugs in samples from the work environment, and to apply these
      methods in validating sampling methodology. A single method for quantifying
      several widely used agents would decrease the number of samples required for
      method development, lower cost, and time of analysis. METHODS: for measuring
      these drugs in workers' urine would also be useful in monitoring personal
      exposure levels. RESULTS: LC-MS/MS methods were developed for individual analysis
      of five antineoplastic drugs in wipe and air sample media projected for use in
      field sampling: cyclophosphamide, ifosfamide, paclitaxel, doxorubicin, and 5
      fluorouracil. Cyclophosphamide, ifosfamide, and paclitaxel were also measured
      simultaneously in some stages of the work. Extraction methods for air and wipe
      samples were developed and tested using the aforementioned analytical methods.
      Good recoveries from the candidate air and wipe sample media for most of the
      compounds, and variable recoveries for test wipe samples depending on the surface
      under study, were observed. Alternate LC-MS/MS methods were also developed to
      detect cyclophosphamide and paclitaxel in urine samples. CONCLUSIONS: The
      sampling and analytical methods were suitable for determining worker exposure to
      antineoplastics via surface and breathing zone contamination in projected surveys
      of healthcare settings.

PMID- 21183557
TI  - Adenosine 2A receptor is protective against renal injury in MRL/lpr mice.
AB  - OBJECTIVE: Adenosine is considered as a potent endogenous anti-inflammatory and
      immunosuppressive molecule. We examined the roles of A2A-adenosine receptor
      (A(2A)R) in the progression of lupus nephritis. METHODS: MRL/lpr mice were given
      a selective A(2A)R agonist, CGS21680 (0.4 mg/kg per day, i.p.) while control mice
      received saline only. After 8 weeks of treatment, mice were sacrificed for
      assessment of functional and histological parameters as well as inflammatory
      infiltration in the kidneys. MCP-1, IFN-gamma, MHC-II and A(2A)R mRNA expression
      was evaluated by RT-PCR. Expression of A(2A)R and nuclear NFkappaB p65 protein
      was determined by Western blot analysis. Levels of anti-dsDNA antibody and IFN
      gamma were measured by ELISA. RESULTS: CGS21680 treatment resulted in significant
      decrease in proteinuria, blood urea and creatinine as well as improvement in
      renal histology. Renal macrophage and T-cell infiltration were significantly
      attenuated in association with suppressed expression of MCP-1, IFN-gamma and MHC
      II. CGS21680 treatment reduced the level of serum anti-dsDNA and renal immune
      complex deposition. CGS21680 inhibited the activation of NFkappaB and suppressed
      the expression of IFN-gamma, MCP-1 and MHC-II in MRL/lpr splenocytes.
      CONCLUSIONS: A(2A)R activation suppressed inflammation in the kidneys of MRL/lpr
      mice and can be considered as a novel therapeutic approach for human lupus
      nephritis.

PMID- 21183558
TI  - Evaluation of adherence to drug treatment in patients with systemic lupus
      erythematosus in Brazil.
AB  - The objectives of this study were to measure the prevalence of adherence to drug
      treatment and analyze associations with characteristics pertaining to the
      treatment, disease, health professionals and services, and socio-demographic
      issues in patients with systemic lupus erythematosus (SLE) in the city of Rio de
      Janeiro, Brazil. A sample of 246 women with SLE was analyzed. The data were
      collected through individual interviews and a review of patient charts. Adherence
      was estimated according to the Morisk criteria, and the associated factors were
      analyzed by hierarchical modeling. The percentage of patients classified as
      adherent to treatment was 31.7%. The reasons cited for non-adherence were:
      carelessness with drug administration times (52.43%), forgetfulness (38.21%),
      adverse drug reaction (13.8%), and interruption of treatment due to improvement
      in symptoms (7.72%). Factors associated with adherence were: behavior towards the
      presence of adverse drug reaction, hematological alterations, presence of
      mucocutaneous manifestations, legibility of the medical prescription, schooling,
      and family support. The study concludes that adherence to drug treatment in SLE
      is a complex and multifactorial phenomenon, and the results corroborate findings
      from studies conducted in developed countries. The hierarchical modeling proved
      to be a good alternative for evaluating adherence, since it allowed visualizing
      the various stages in the analysis.

PMID- 21183559
TI  - Studies of Filipino patients with systemic lupus erythematosus: autoantibody
      profile of first-degree relatives.
AB  - This study surveyed the frequency of autoantibodies among un-affected first
      degree relatives (FDRs) of Filipino systemic lupus erythematosus (SLE) patients
      compared with healthy un-related Filipino controls. The sensitivity, specificity
      and predictive value of the autoantibodies for SLE diagnosis were also assessed
      in this Filipino cohort. Filipino patients included in the University of Santo
      Tomas (UST) Lupus Database and un-affected FDRs were recruited. Healthy controls
      included those with no known personal or family history of autoimmune disease.
      The following autoantibodies were tested in all subjects: anti-nuclear antibody
      (ANA), anti-dsDNA, anti-Ro/SSA, anti-chromatin, anti-thyroid microsome, and anti
      cardiolipin antibodies. Participants included 232 SLE patients, 546 FDRs, and 221
      healthy controls. Median age of patients was 27 (range 8-66) years with median
      disease duration of 27.5 (range 1-292) months. Median age of FDRs was 42.0 (range
      5-87) years. Compared with healthy controls, there were significantly more FDRs
      with positive ANA at titers 1 : 40 to 1 : 160 (p < 0.001) and 1 : 320 (p =
      0.003), anti-Ro/SSA (4.94% versus 0.45%, p = 0.003), and anti-dsDNA >= 5.0 IU/ml
      (4.58% versus 1.36%, p = 0.031). ANA titer >=1  :  160, anti-dsDNA, anti-Ro/SSA
      and anti-chromatin had the highest predictive value for SLE diagnosis. These
      findings reinforce the role of genetic influence in SLE risk among Filipinos,
      with a significant proportion of un-affected FDRs of SLE patients testing
      positive for autoantibodies compared with healthy Filipino controls. A
      longitudinal observational study in this same cohort will determine which
      proportion of these un-affected FDRs will evolve into clinical SLE disease in the
      future.

PMID- 21183560
TI  - Juvenile systemic lupus erythematosus in the Sultanate of Oman: clinical and
      immunological comparison between familial and non-familial cases.
AB  - Consanguineous marriage is quite prevalent in the Sultanate of Oman, with up to
      45% of marriages being consanguineous. The aim of this study was to determine
      demographic, clinical and serological characteristics between familial and non
      familial cases of juvenile systemic lupus erythematosus (SLE) in a highly
      consanguineous region such as Oman. Hospital medical records were retrospectively
      reviewed for 44 consecutive children with juvenile SLE seen at Sultan Qaboos
      University Hospital, 16 with familial SLE and 28 with non-familial SLE. All the
      children included in the study were Omani, diagnosed before 13 years of age, and
      fulfilled the 1982 revised ACR criteria. Analyses were performed using
      descriptive statistics. There were largely no significant differences in the
      clinical and serological manifestations between the two cohorts. However, the
      familial SLE group was associated with worse SLEDAI score at onset of diagnosis
      compared with the non-familial cohort (12 vs. 17; p = 0.003) suggesting a greater
      severity of disease in the familial group. Even though the rate of familial SLE
      is higher in Oman (36%) compared with the Western world (10-12%), it appears that
      familial and non-familial SLE cases are in fact similar disease entities in both
      the West and the Middle Eastern countries.

PMID- 21183561
TI  - Systemic lupus erythematosus following vaccination against 2009 influenza A
      (H1N1).

PMID- 21183562
TI  - Perceptions and measurements of physical activity in patients with systemic lupus
      erythematosus.
AB  - Promoting physical activity should be a priority for patients with systemic lupus
      erythematosus (SLE) because a sedentary lifestyle compounds patients' already
      disproportionately high risk for cardiovascular events and other adverse health
      outcomes. The objectives of this pilot study were to assess physical activity in
      50 patients with SLE and to compare activity levels with clinical and
      psychosocial variables, such as fatigue, depressive symptoms, and social support
      and stress. Patients were asked open-ended questions about physical activity, and
      responses were coded according to Grounded Theory. Patients then completed the
      Paffenbarger Physical Activity and Exercise Index, a survey of lifestyle energy
      expenditure reported in kilocalories/week, performed a 2-minute walk test
      according to a standard protocol, and completed questionnaires measuring fatigue,
      depressive symptoms and social support and stress. Most patients (92%) were
      women, had a mean age of 45 years, and did not have extensive SLE. In response to
      open-ended questions, patients reported they avoided physical activity because
      they did not want to exacerbate SLE in the short term. However, if they could
      overcome initial hurdles, 46 patients (92%) thought physical activity ultimately
      would improve SLE symptoms. Walking was the preferred activity and 45 (90%)
      thought they could walk more. According to the Paffenbarger Index, mean energy
      expenditure was 1466 +/- 1366 kilocalories/week and mean time spent in moderate
      intensity activity was 132 +/- 222 min/week. In total, 18 patients (36%) and 14
      patients (28%) met physical activity goals for these values, respectively. Mean
      distance walked during the 2-minute test was 149 +/- 28 m, equivalent to two
      blocks, which is similar to reports for stable patients with other chronic
      diseases. Patients with more social stress and more fatigue reported less
      physical activity. We conclude that the proportion of patients meeting physical
      activity goals was low; however, patients performed well on a standard walking
      test. Most patients believed physical activity provided long-term benefits for
      SLE and that they could be more physically active.

PMID- 21183563
TI  - Chronic autoimmune urticaria as the first manifestation of juvenile systemic
      lupus erythematosus.
AB  - Chronic urticaria (daily or almost daily symptoms lasting for more than six
      weeks) is characterized by wheals and erythema, with or without itching. A few
      case reports have shown chronic autoimmune urticaria at the beginning of systemic
      lupus erythematosus (SLE), particularly in adults. However, the prevalence of
      this manifestation in a lupus paediatric population was not studied. During 27
      consecutive years, 5419 patients were followed up at our University Hospital and
      271 (5%) had juvenile SLE (American College of Rheumatology criteria). Two of
      them (0.7%) had chronic and painless autoimmune urticaria as the first
      manifestation of juvenile SLE, and were reported herein. One case was a five-year
      old female with continuous widespread urticaria (duration 120 days), antinuclear
      antibodies (ANA) 1:640 (dense fine speckled pattern) and elevated complement
      levels. The juvenile SLE diagnosis was established after one year. The other case
      was a 13-year old female who had chronic widespread urticaria (lasting 45 days),
      ANA 1:160 (fine speckled pattern) and normal complement levels. The juvenile SLE
      diagnosis was established after three years. In conclusion, chronic autoimmune
      urticaria is very rare and may be the first lupus manifestation, particularly
      associated with the presence of autoantibodies. This study reinforces the
      importance of a rigorous follow-up in children and adolescents suffering from
      autoimmune urticaria due to the possibility of connective tissue disorders, such
      as paediatric lupus.

PMID- 21183564
TI  - The anti-DNA story.

PMID- 21183566
TI  - Immunity for expert witnesses is under threat from a case coming to Supreme
      Court.

PMID- 21183565
TI  - Methylphenidate has dose-dependent negative effects on rat spermatogenesis:
      decreased round spermatids and testicular weight and increased p53 expression and
      apoptosis.
AB  - In the present study, we aimed to evaluate the possible effects of
      methylphenidate on rat testes. Forty-two Wistar rats were randomly distributed
      into three experimental groups of 14 rats each. For 90 days, each group via
      gavage received the following: group 1 = tap water (control group), group 2 = 5
      mg/kg/day of ritalin (methylphenidate, MPH), and group 3 = 10 mg/kg/day of
      ritalin. After sacrificing the animals, the body weights as well as the absolute
      and relative testicular weights were measured. Testes were sampled, fixed, and
      processed and, by histopathological examination, quantitative morphometric
      analysis of Sertoli cells, spermatocytes, and spermatids was performed in stages
      II, V, and XII. Immunohistochemistry was performed for transforming growth factor
      (TGF)-beta1 and p53, and the apoptotic index was assessed through the TUNEL
      method. Group 2 had a reduction of round spermatids in stage II. Group 3 had
      reduction in both stage II and stage V spermatids, as well as lower testicular
      weight. The p53 expression was increased in group 3. In groups 2 and 3, the TGF
      beta1 expression was reduced and the apoptotic index by TUNEL was increased. Body
      weights remained stable on either group. Our results showed that methylphenidate
      might negatively affect spermatogenesis not only by reducing testicular weight
      and amount of round spermatids but also by increasing apoptotic death and p53
      activation. The findings of the study, however, must be cautiously interpreted.

PMID- 21183567
TI  - Massive scale-up of malaria control in endemic nations must be sustained, says
      WHO.

PMID- 21183571
TI  - Occupational tellurium exposure and garlic odour.
AB  - BACKGROUND: Few studies have considered garlic odour as a socially important
      outcome of occupational tellurium (Te) exposure or concurrent exposures, and most
      known guidelines focus on other signs and symptoms (e.g. weight loss and
      somnolence). This study considers workers exposed to tellurium and selenium (Se)
      at an Ontario, Canada silver refinery. AIMS: To establish the relation of urinary
      tellurium concentrations to reporting garlic odour, while considering other work
      related factors such as concurrent urinary selenium concentrations. METHODS:
      Historical surveillance records of urinary analyses for tellurium and selenium
      concentrations (MUmol Te or Se/mol creatinine in urine) and symptom self-reports
      were used. Records were available from December 1986 to June 2002. Logistic
      regression models were fitted using age at sampling, tellurium and selenium urine
      concentration and duration of employment. Individual main effects were age
      adjusted and the final model was fitted for tellurium and selenium urine
      concentration and duration of employment. RESULTS: Urinary tellurium
      concentration was significantly associated with garlic odour reporting (odds
      ratio = 1.74, 95% confidence interval 1.01-2.97, P < 0.05). Furthermore, the
      likelihood of reporting garlic odour rose as workers reached urinary tellurium
      concentrations >1 MUmol/mol creatinine. CONCLUSIONS: Tellurium urinary
      concentrations of <1 MUmol/mol creatinine appear to limit, but not eliminate, the
      likelihood of reporting garlic odour. Future studies should consider the effect
      of concurrent selenium exposure as well as other workplace factors and hygiene.

PMID- 21183572
TI  - Yersinia pseudotuberculosis mntH functions in intracellular manganese
      accumulation, which is essential for virulence and survival in cells expressing
      functional Nramp1.
AB  - Manganese has an important yet undefined role in the virulence of many bacterial
      pathogens. In this study we confirm that a null mutation in Yersinia
      pseudotuberculosis mntH reduces intracellular manganese accumulation. An mntH
      mutant was susceptible to killing by reactive oxygen species when grown under
      manganese-limited conditions. The mntH mutant was defective in survival and
      growth in macrophages expressing functional Nramp1, but in macrophages deficient
      in Nramp the bacteria were able to survive and replicate. In Galleria mellonella,
      the mntH mutant was attenuated. Taken together, these data suggest a role for
      manganese in Y. pseudotuberculosis during macrophage intracellular survival,
      protecting the bacteria from the antimicrobial products released during the
      respiratory burst.

PMID- 21183573
TI  - Clp-dependent proteolysis of the LexA N-terminal domain in Staphylococcus aureus.
AB  - The SOS response is governed by the transcriptional regulator LexA and is
      elicited in many bacterial species in response to DNA damaging conditions.
      Induction of the SOS response is mediated by autocleavage of the LexA repressor
      resulting in a C-terminal dimerization domain (CTD) and an N-terminal DNA-binding
      domain (NTD) known to retain some DNA-binding activity. The proteases responsible
      for degrading the LexA domains have been identified in Escherichia coli as ClpXP
      and Lon. Here, we show that in the human and animal pathogen Staphylococcus
      aureus, the ClpXP and ClpCP proteases contribute to degradation of the NTD and to
      a lesser degree the CTD. In the absence of the proteolytic subunit, ClpP, or one
      or both of the Clp ATPases, ClpX and ClpC, the LexA domains were stabilized after
      autocleavage. Production of a stabilized variant of the NTD interfered with
      mitomycin-mediated induction of sosA expression while leaving lexA unaffected,
      and also significantly reduced SOS-induced mutagenesis. Our results show that
      sequential proteolysis of LexA is conserved in S. aureus and that the NTD may
      differentially regulate a subset of genes in the SOS regulon.

PMID- 21183574
TI  - The nitrogen interaction network in Synechococcus WH5701, a cyanobacterium with
      two PipX and two P(II)-like proteins.
AB  - Nitrogen regulation involves the formation of different types of protein
      complexes between signal transducers and their transcriptional or metabolic
      targets. In oxygenic phototrophs, the signal integrator P(II) activates the
      enzyme N-acetyl-l-glutamate kinase (NAGK) by complex formation. P(II) also
      interacts with PipX, a protein with a tudor-like domain that mediates contacts
      with P(II) and with the transcriptional regulator NtcA, to which it binds to
      increase its activity. Here, we use a combination of in silico, yeast two-hybrid
      and in vitro approaches to investigate the nitrogen regulation network of
      Synechococcus WH5701, a marine cyanobacterium with two P(II) (GlnB_A and GlnB_B)
      and two PipX (PipX_I and PipX_II) proteins. Our results indicate that GlnB_A is
      functionally equivalent to the canonical P(II) protein from Synechococcus
      elongatus. GlnB_A interacted with PipX and NAGK proteins and stimulated NAGK
      activity, counteracting arginine inhibition. GlnB_B had only a slight stimulatory
      effect on NAGK activity, but its potential to bind effectors and form
      heterotrimers in Synechococcus WH5701 indicates additional regulatory functions.
      PipX_II, and less evidently PipX_I, specifically interacted with GlnB_A and NtcA,
      supporting a role for both Synechococcus WH5701 PipX proteins in partner swapping
      with GlnB_A and NtcA.

PMID- 21183576
TI  - Occupational medicine training into the 21st century.

PMID- 21183577
TI  - Constantin Meunier. Industrie (industry) 1896.

PMID- 21183578
TI  - Occupational travel.
AB  - BACKGROUND: This review summarizes the available evidence on travel-related
      illness and injury for overseas travellers and, where available, evaluates the
      literature on occupational travellers. METHODS: The studies evaluated include
      those published in international scientific literature since 1980 and were
      identified through a search of relevant databases using selected keywords.
      RESULTS: A high proportion of travellers experience health problems. While the
      majority of problems are minor, they can cause disruption to travel plans, and a
      small proportion can result in hospital admission or death. Data on occupational
      travellers are limited but reveal similar findings, although higher rates of
      illness and injury are often reported and psychological factors appear to be more
      prominent. This is particularly the case for expatriates. CONCLUSIONS: While data
      on general travellers can be used to make valid inferences about the travel
      related illness or injury in occupational travellers, there are some important
      differences between the two groups, which need to be considered when making
      comparisons. Further research in this area is required to evaluate the additional
      risks to those who travel overseas for work.

PMID- 21183579
TI  - Coming to the end of the road in occupational health--lessons from cancer care.

PMID- 21183580
TI  - Those two impostors.

PMID- 21183581
TI  - Testing new regimens in patients with advanced soft tissue sarcoma: analysis of
      publications from the last 10 years.
AB  - BACKGROUND: The prognosis of advanced soft tissue sarcoma remains poor. Many
      phase II trials investigating new regimens have been published in the last 10
      years. MATERIALS AND METHODS: Full English-language reports of phase II clinical
      trials from January 1999 to October 2009 have been reviewed. We have defined
      those that provided 3- and 6-month progression-free survival rates (PFSR) >39%
      and 14%, respectively, as promising second-line regimens. For studies enrolling
      both chemonaive and pretreated patients, we have compared the reported PFSR3 to
      the expected PFSR3 of an active treatment administered in the same proportions of
      pretreated and nonpretreated patients. RESULTS: Forty-nine trials were
      identified. Among the trials investigating new regimens in pretreated patients
      alone, the promising second-line regimens were ifosfamide, brostallicin,
      pazopanib (except in liposarcoma), temozolomide, trabectedin, dacarbazine
      gemcitabine and docetaxel (Taxotere)-gemcitabine combinations (in uterine
      leiomyosarcoma). Among the trials enrolling both chemonaive and pretreated
      patients, most regimens reached the level of efficacy; moreover, in three trials,
      the reported PFSR3 was particularly high: weekly paclitaxel (Taxol) in
      angiosarcoma, docetaxel-gemcitabine combination (in uterine leiomyosarcoma) and
      oral perifosine. CONCLUSIONS: In the past 10 years, several drugs or combinations
      have demonstrated promising activity in exploratory phase II trials and warrant
      further investigation in appropriate phase III trials.

PMID- 21183582
TI  - Movement kinematics of prepotent response suppression in aging during conflict
      adaptation.
AB  - OBJECTIVES: The purpose of the current study was to explore the role of
      adjustments in motor control and conflict adaptation in younger and older adults'
      prepotent response suppression. METHODS: Participants performed repeated pairs of
      key-presses on a piano-type keyboard as well as key-presses that conflicted with
      that prepotent pair. We used motion capture to assess cognitive and motor
      contributions to conflicting responses presented once, twice, or three times
      within single trials. RESULTS: Older adults performed the first conflicting
      response in a series as well as young adults but at a cost to prepotent response
      performance. Younger adults improved performance with increased conflict
      frequency, whereas older adults did not. Older adults spent less time planning
      and more time executing their conflicting responses, with the opposite pattern in
      younger adults. DISCUSSION: Overall, increasing the frequency of conflicting
      response presentation was detrimental to older but not to younger adults'
      prepotent response performance. In addition, the results indicate an age-related
      decline in conflict adaptation. The results are discussed in terms of current
      models of cognitive control.

PMID- 21183583
TI  - The Luoping biota: exceptional preservation, and new evidence on the Triassic
      recovery from end-Permian mass extinction.
AB  - The timing and nature of biotic recovery from the devastating end-Permian mass
      extinction (252 Ma) are much debated. New studies in South China suggest that
      complex marine ecosystems did not become re-established until the middle-late
      Anisian (Middle Triassic), much later than had been proposed by some. The
      recently discovered exceptionally preserved Luoping biota from the Anisian Stage
      of the Middle Triassic, Yunnan Province and southwest China shows this final
      stage of community assembly on the continental shelf. The fossil assemblage is a
      mixture of marine animals, including abundant lightly sclerotized arthropods,
      associated with fishes, marine reptiles, bivalves, gastropods, belemnoids,
      ammonoids, echinoderms, brachiopods, conodonts and foraminifers, as well as
      plants and rare arthropods from nearby land. In some ways, the Luoping biota
      rebuilt the framework of the pre-extinction latest Permian marine ecosystem, but
      it differed too in profound ways. New trophic levels were introduced, most
      notably among top predators in the form of the diverse marine reptiles that had
      no evident analogues in the Late Permian. The Luoping biota is one of the most
      diverse Triassic marine fossil Lagerstatten in the world, providing a new and
      early window on recovery and radiation of Triassic marine ecosystems some 10 Myr
      after the end-Permian mass extinction.

PMID- 21183584
TI  - DiNAMIC: a method to identify recurrent DNA copy number aberrations in tumors.
AB  - MOTIVATION: DNA copy number gains and losses are commonly found in tumor tissue,
      and some of these aberrations play a role in tumor genesis and development.
      Although high resolution DNA copy number data can be obtained using array-based
      techniques, no single method is widely used to distinguish between recurrent and
      sporadic copy number aberrations. RESULTS: Here we introduce Discovering Copy
      Number Aberrations Manifested In Cancer (DiNAMIC), a novel method for assessing
      the statistical significance of recurrent copy number aberrations. In contrast to
      competing procedures, the testing procedure underlying DiNAMIC is carefully
      motivated, and employs a novel cyclic permutation scheme. Extensive simulation
      studies show that DiNAMIC controls false positive discoveries in a variety of
      realistic scenarios. We use DiNAMIC to analyze two publicly available tumor
      datasets, and our results show that DiNAMIC detects multiple loci that have
      biological relevance. AVAILABILITY: Source code implemented in R, as well as text
      files containing examples and sample datasets are available at
      http://www.bios.unc.edu/research/genomic_software/DiNAMIC.

PMID- 21183585
TI  - CompleteMOTIFs: DNA motif discovery platform for transcription factor binding
      experiments.
AB  - CompleteMOTIFs (cMOTIFs) is an integrated web tool developed to facilitate
      systematic discovery of overrepresented transcription factor binding motifs from
      high-throughput chromatin immunoprecipitation experiments. Comprehensive
      annotations and Boolean logic operations on multiple peak locations enable users
      to focus on genomic regions of interest for de novo motif discovery using tools
      such as MEME, Weeder and ChIPMunk. The pipeline incorporates a scanning tool for
      known motifs from TRANSFAC and JASPAR databases, and performs an enrichment test
      using local or precalculated background models that significantly improve the
      motif scanning result. Furthermore, using the cMOTIFs pipeline, we demonstrated
      that multiple transcription factors could cooperatively bind to the upstream of
      important stem cell differentiation regulators. AVAILABILITY:
      http://cmotifs.tchlab.org.

PMID- 21183586
TI  - Vegetarian compared with meat dietary protein source and phosphorus homeostasis
      in chronic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: Patients with advanced chronic kidney disease (CKD)
      are in positive phosphorus balance, but phosphorus levels are maintained in the
      normal range through phosphaturia induced by increases in fibroblast growth
      factor-23 (FGF23) and parathyroid hormone (PTH). This provides the rationale for
      recommendations to restrict dietary phosphate intake to 800 mg/d. However, the
      protein source of the phosphate may also be important. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: We conducted a crossover trial in nine patients
      with a mean estimated GFR of 32 ml/min to directly compare vegetarian and meat
      diets with equivalent nutrients prepared by clinical research staff. During the
      last 24 hours of each 7-day diet period, subjects were hospitalized in a research
      center and urine and blood were frequently monitored. RESULTS: The results
      indicated that 1 week of a vegetarian diet led to lower serum phosphorus levels
      and decreased FGF23 levels. The inpatient stay demonstrated similar diurnal
      variation for blood phosphorus, calcium, PTH, and urine fractional excretion of
      phosphorus but significant differences between the vegetarian and meat diets.
      Finally, the 24-hour fractional excretion of phosphorus was highly correlated to
      a 2-hour fasting urine collection for the vegetarian diet but not the meat diet.
      CONCLUSIONS: In summary, this study demonstrates that the source of protein has a
      significant effect on phosphorus homeostasis in patients with CKD. Therefore,
      dietary counseling of patients with CKD must include information on not only the
      amount of phosphate but also the source of protein from which the phosphate
      derives.

PMID- 21183587
TI  - Repeat peritonitis in peritoneal dialysis: retrospective review of 181
      consecutive cases.
AB  - BACKGROUND AND OBJECTIVES: The clinical behavior of repeat-peritonitis episodes,
      defined as peritonitis with the same organism occurring more than 4 weeks after
      completion of therapy for a prior episode, is poorly understood. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: We compared outcomes of 181 episodes of repeat
      peritonitis from 1995 to 2009 (Repeat Group) with 91 episodes of relapsing
      peritonitis (Relapsing Group) and 125 episodes of peritonitis preceded 4 weeks or
      longer by another episode with a different organism (Control Group). RESULTS: In
      Repeat Group, 24% were due to Staphylococcus aureus, as compared with 5.5% in
      Relapsing Group and 15% in Control Group. The majority of the organisms causing
      relapsing peritonitis were Gram negative (62%), whereas the majority of that in
      Repeat Group were Gram positive (56%). Repeat Group had a lower complete-cure
      rate (70.7% versus 54.9%) than Relapsing Group, but rates of primary response,
      catheter removal, and mortality were similar. Repeat Group had a higher primary
      response rate (89.0% versus 73.6%) and a lower rate of catheter removal (6.1%
      versus 15.2%) than Control Group, whereas the complete-cure rate and mortality
      were similar. Repeat Group had a higher risk of developing relapsing (14.3%
      versus 2.2%) and repeat peritonitis (26.1% versus 5.4%) than Control Group,
      whereas the risk of recurrent peritonitis was similar. CONCLUSIONS: Repeat
      peritonitis is a distinct clinical entity. Although repeat-peritonitis episodes
      generally have a satisfactory response to antibiotic, they have a substantial
      risk of developing further relapsing or repeat peritonitis.

PMID- 21183588
TI  - The Family Talk About Smoking (FTAS) paradigm: new directions for assessing
      parent-teen communications about smoking.
AB  - INTRODUCTION: Smoking experimentation represents transient risk taking for some
      youth, whereas for others, it is the onset of a chronic smoking trajectory.
      However, distinguishing these groups during the experimentation phase has proved
      challenging. We theorized that variations in parent and teen discourse about
      smoking might be informative for characterizing this heterogeneity. However,
      standardized methods for direct assessments of these family processes have been
      lacking. METHODS: We examined the predictive utility of directly observed facets
      of smoking-specific communication for predicting persistence of teen smoking
      experimentation using a novel method, the Family Talk About Smoking (FTAS)
      paradigm. The FTAS was tested in a sample of 344 teens with a history of smoking
      experimentation during interactions with their mothers and fathers. Level of
      disapproval, smoking expectancies, elaboration of consequences, and quality of
      personal disclosure were coded during videotaped parent-teen discussions about
      smoking. RESULTS: Patterns of observed smoking-specific communication varied by
      teen and parent smoking status. Predictive validity of the FTAS for teen
      persistent experimentation was demonstrated, net effects of reported smoking
      specific socialization, general quality of communication, and parental smoking
      status. Teen smoking expectancies, disclosure, and disapproval predicted teen
      persistent experimentation with some differences based on whether interactions
      were with mothers or fathers. Prediction of persistent experimentation by
      observed maternal disclosure and elaboration of consequences was moderated by
      maternal smoking status. CONCLUSIONS: Direct observations show promise for
      generating detailed characterization of individual differences in patterns of
      family communication about smoking. Implications for targeted prevention and
      future research are discussed.

PMID- 21183589
TI  - Tobacco use among American Indian or Alaska Native middle- and high-school
      students in the United States.
AB  - INTRODUCTION: An estimated 0.5 million American Indian or Alaska Native (AI/AN)
      adolescents under the age of 18 years smoked cigarettes during their entire
      lifetime. Using a national sample of AI/AN middle- and high-school students, this
      study examines prevalence rates and relative impacts of individual, familial, and
      social predictors of different types of tobacco use. METHODS: A national sample
      of 305 (weighted N = 142,989) AI/AN middle- and high-school students in Grades 6
      through 12 were selected from the 2006 National Youth Tobacco Survey. RESULTS:
      During their entire life, most of the respondents used cigarettes (54%), followed
      by cigars (24%), smokeless tobacco (16%), pipes (13%), and menthol cigarettes
      (12%). One in 3 (32%) used 2 or more forms of tobacco. High-school students
      reported significantly higher for all types of tobacco use than middle-school
      students, while the rates did not differ by gender. Multivariate analyses showed
      that age, family members' smoking, and refusal to smoke predicted tobacco users
      with one product. Family members' smoking and refusal to smoke remained
      significant in predicting more than 2 forms of tobacco use (polytobacco users),
      while age was no longer significant. School truancy and receptivity to tobacco
      marketing uniquely predicted polytobacco users. CONCLUSIONS: Findings underscore
      that tobacco control programs for AI/AN students need to address the multiple
      predictors of different types of tobacco use. Implications of the findings are
      discussed.

PMID- 21183590
TI  - The Th17-defining transcription factor RORgammat promotes glomerulonephritis.
AB  - Although Th17 responses may contribute to the pathogenesis of glomerulonephritis,
      whether the key transcription factor in Th17 cell development, RORgammat, also
      promotes glomerulonephritis is unknown. Here, we induced crescentic
      glomerulonephritis in wild-type and RORgammat-deficient (RORgammat(-/-)) mice.
      RORgammat(-/-) mice were protected from disease, with reduced histologic and
      functional injury and decreased leukocyte infiltration. Because RORgammat(-/-)
      mice lack lymph nodes, which may influence the development of nephritis, we
      performed cell-transfer studies. We reconstituted Rag1(-/-) mice, which lack
      adaptive immunity but otherwise have normal architecture of the lymphatic system,
      with splenocytes from naive wild-type or RORgammat(-/-) mice. Mice receiving wild
      type splenocytes exhibited high mortality from renal failure after induction of
      nephritis whereas mice receiving RORgammat(-/-) cells were protected. To
      determine the effect of RORgammat deficiency specifically in T helper cells, we
      isolated naive CD4(+) T cells from wild-type and RORgammat(-/-) mice and
      transferred them into Rag1(-/-) animals. Recipients of wild-type CD4(+) T cells
      developed severe glomerulonephritis whereas recipients of RORgammat(-/-) cells
      developed less severe disease. To exclude effects of altered regulatory T cell
      (Treg) development caused by RORgammat deficiency, we transferred naive CD4(+) T
      cells depleted of Tregs into Rag1(-/-) mice. Recipients of wild-type, Treg
      depleted, CD4(+) T cells developed severe glomerulonephritis whereas recipients
      of RORgammat(-/-), Treg-depleted CD4(+) T cells did not. Taken together, this
      study demonstrates that RORgammat promotes the development of crescentic
      glomerulonephritis by directing nephritogenic Th17 responses.

PMID- 21183591
TI  - TGF-alpha mediates genetic susceptibility to chronic kidney disease.
AB  - The mechanisms of progression of chronic kidney disease (CKD) are poorly
      understood. Epidemiologic studies suggest a strong genetic component, but the
      genes that contribute to the onset and progression of CKD are largely unknown.
      Here, we applied an experimental model of CKD (75% excision of total renal mass)
      to six different strains of mice and found that only the FVB/N strain developed
      renal lesions. We performed a genome-scan analysis in mice generated by back
      crossing resistant and sensitive strains; we identified a major susceptibility
      locus (Ckdp1) on chromosome 6, which corresponds to regions on human chromosome 2
      and 3 that link with CKD progression. In silico analysis revealed that the locus
      includes the gene encoding the EGF receptor (EGFR) ligand TGF-alpha. TGF-alpha
      protein levels markedly increased after nephron reduction exclusively in FVB/N
      mice, and this increase preceded the development of renal lesions. Furthermore,
      pharmacologic inhibition of EGFR prevented the development of renal lesions in
      the sensitive FVB/N strain. These data suggest that variable TGF-alpha expression
      may explain, in part, the genetic susceptibility to CKD progression. EGFR
      inhibition may be a therapeutic strategy to counteract the genetic predisposition
      to CKD.

PMID- 21183592
TI  - Mouse model for Lowe syndrome/Dent Disease 2 renal tubulopathy.
AB  - The Lowe oculocerebrorenal syndrome is an X-linked disorder characterized by
      congenital cataracts, cognitive disability, and proximal tubular dysfunction.
      Both this syndrome and Dent Disease 2 result from loss-of-function mutations in
      the OCRL gene, which encodes a type II phosphatidylinositol bisphosphate 5
      phosphatase. Ocrl-deficient mice are unaffected, however, which we believe
      reflects a difference in how humans and mice cope with the enzyme deficiency.
      Inpp5b and INPP5B, paralogous autosomal genes that encode another type II
      phosphoinositide 5-phosphatase in mice and humans, respectively, might explain
      the distinct phenotype in the two species because they are the closest paralogs
      to Ocrl and OCRL in their respective genomes yet differ between the two species
      with regard to expression and splicing. Here, we generated Ocrl(-/-) mice that
      express INPP5B but not Inpp5b. Similar to the human syndromes, all showed reduced
      postnatal growth, low molecular weight proteinuria, and aminoaciduria. Thus, we
      created an animal model for OCRL and Dent Disease 2 tubulopathy by humanizing a
      modifier paralog in mice already carrying the mutant disease gene.

PMID- 21183594
TI  - Fluid shear stress primes mouse embryonic stem cells for differentiation in a
      self-renewing environment via heparan sulfate proteoglycans transduction.
AB  - Shear stress is a ubiquitous environmental cue experienced by stem cells when
      they are being differentiated or expanded in perfusion cultures. However, its
      role in modulating self-renewing stem cell phenotypes is unclear, since shear is
      usually only studied in the context of cardiovascular differentiation. We used a
      multiplex microfluidic array, which overcomes the limitations of macroperfusion
      systems in shear application throughput and precision, to initiate a
      comprehensive, quantitative study of shear effects on self-renewing mouse
      embryonic stem cells (mESCs), where shear stresses varying by >1000 times (0.016
      16 dyn/cm(2)) are applied simultaneously. When compared with static controls in
      the presence or absence of a saturated soluble environment (i.e., mESC
      conditioned medium), we ascertained that flow-induced shear stress specifically
      up-regulates the epiblast marker Fgf5. Epiblast-state transition in mESCs
      involves heparan sulfate proteoglycans (HSPGs), which have also been shown to
      transduce shear stress in endothelial cells. By disrupting (with sulfation
      inhibitors and heparinase) and partially reconstituting (with heparin) HSPG
      function, we show that mESCs also mechanically sense shear stress via HSPGs to
      modulate Fgf5 expression. This study demonstrates that self-renewing mESCs
      possess the molecular machinery to sense shear stress and provides quantitative
      shear application benchmarks for future scalable stem cell culture systems.

PMID- 21183593
TI  - Neutrophil responses to staphylococcal pathogens and commensals via the formyl
      peptide receptor 2 relates to phenol-soluble modulin release and virulence.
AB  - The mechanisms used by the immune system to discriminate between pathogenic and
      commensal bacteria have remained largely unclear. Recently, we have shown that
      virulence of Staphylococcus aureus depends on secretion of phenol-soluble modulin
      (PSM) peptides that disrupt neutrophils at micromolar concentrations. Moreover,
      all S. aureus PSMs stimulate and attract neutrophils at nanomolar concentrations
      via interaction with the formyl-peptide receptor 2 (FPR2). Here, we demonstrate
      that FPR2 allows neutrophils to adjust their responses in relation to the
      aggressiveness of staphylococcal species, which differ largely in their capacity
      to infect or colonize humans and animals. PSM-related peptides were detected in
      all human and animal pathogenic staphylococci, but were absent from most
      commensal species. Three PSMbeta-like peptides produced by the serious human
      pathogen Staphylococcus lugdunensis were identified as the previously described
      S. lugdunensis-synergistic hemolysins (SLUSHs). SLUSHs attracted and stimulated
      human leukocytes in a FPR2-dependent manner, indicating that FPR2 is a general
      receptor for all PSM-like peptide toxins. Remarkably, the release of PSMs
      correlated closely with the apparent capacity of staphylococcal species to cause
      invasive infections and with their ability to activate FPR2. These findings
      suggest that the innate immune system may be able to respond in different ways to
      pathogenic or innocuous staphylococci by monitoring the presence of PSMs via
      FPR2.

PMID- 21183595
TI  - Utility of reverse transcriptase PCR and DNA-PCR in the diagnosis of female
      genital tuberculosis.
AB  - This study was designed to test the utility of mRNA-based RT-PCR to detect viable
      bacilli, indicating active tubercular involvement, and DNA-PCR to detect present
      or past infection in the diagnosis of active female genital tuberculosis (TB)
      infection. A total of 200 subjects with complaints of infertility were enrolled
      in the study. Multiple sampling was done. One hundred and forty-three endometrial
      aspirate (EA), 94 peritoneal fluid/peritoneal washing (PF/PW) and six cornual
      biopsy (CB) specimens were collected for diagnosis using microscopy, culture, RT
      PCR and DNA-PCR and results were compared with laparoscopic findings. RT-PCR and
      culture were concordant [positive in four (2.8%) EA specimens] signalling
      sampling from the site of active infection. Smear microscopy showed a poor
      detection rate while DNA-PCR showed high positivity. Sixty-one (44.85%) EA
      specimens, nine (9.57%) PF/PW specimens and two (33.33%) CB specimens were
      positive by DNA-PCR. Genital TB causing infertility (localized or secondary to TB
      elsewhere) can be picked up early by DNA-PCR, when it can be completely cured
      prior to the appearance of florid disease.

PMID- 21183596
TI  - Development of a dry reagent-based triplex PCR for the detection of toxigenic and
      non-toxigenic Vibrio cholerae.
AB  - Vibrio cholerae has caused severe outbreaks of cholera worldwide with thousands
      of recorded deaths annually. Molecular diagnosis for cholera has become
      increasingly important for rapid detection of cholera as the conventional methods
      are time-consuming and labour intensive. However, traditional PCR tests still
      require cold-chain transportation and storage as well as trained personnel to
      perform, which makes them user-unfriendly. The aim of this study was to develop a
      thermostabilized triplex PCR test for cholera which is in a ready-to-use form and
      requires no cold chain. The PCR test specifically detects both toxigenic and non
      toxigenic strains of V. cholerae based on the cholera toxin A (ctxA) and outer
      membrane lipoprotein (lolB) genes. The thermostabilized triplex PCR also
      incorporates an internal amplification control that helps to check for PCR
      inhibitors in samples. PCR reagents and the specific primers were lyophilized
      into a pellet form in the presence of trehalose, which acts as an enzyme
      stabilizer. The triplex PCR was validated with 174 bacteria-spiked stool
      specimens and was found to be 100 % sensitive and specific. The stability of the
      thermostabilized PCR was evaluated using the Q10 method and it was found to be
      stable for approximately 7 months at 24  degrees C. The limit of detection of the
      thermostabilized triplex PCR assay was 2*10(4) c.f.u. at the bacterial cell level
      and 100 pg DNA at the genomic DNA level, comparable to conventional PCR methods.
      In conclusion, a rapid thermostabilized triplex PCR assay was developed for
      detecting toxigenic and non-toxigenic V. cholerae which requires minimal
      pipetting steps and is cold chain-free.

PMID- 21183597
TI  - Effects of antibiotics on Chlamydia trachomatis viability as determined by real
      time quantitative PCR.
AB  - The objective of this study was to determine the effect of antibiotics on
      Chlamydia trachomatis viability by using a quantitative real-time PCR assay that
      measured DNA replication and mRNA transcription of the structural omp1 and omp2
      genes, 16S rRNA and the groEL1 gene with and without antibiotics. Ofloxacin,
      moxifloxacin, azithromycin and doxycycline were tested against the serovar D and
      L2 reference strains and a derivative mutant resistant to fluoroquinolones, L2
      OFXR, obtained by in vitro selection. Using DNA quantification, the antibiotic
      MIC was calculated when the number of DNA copies was equal to that of the
      chlamydial inoculum at time zero. This method allowed the easy determination of
      MICs by DNA quantification of the four selected genes and gave similar results to
      those obtained by immunofluorescence staining without biased interpretation. By
      using cDNA quantification, the lowest antibiotic concentration for which no RNA
      was transcribed corresponded to the minimum bactericidal concentration. C.
      trachomatis still transcribed the16S rRNA and groEL1 genes, even at
      concentrations well above the MIC, showing a bacteriostatic effect for all
      antibiotics tested. This method allows the study of antibiotic activity on growth
      and viability of C. trachomatis by DNA and RNA quantification at the same time
      without additional cell-culture passaging.

PMID- 21183598
TI  - Distribution of Chlamydia trachomatis genovars among youths and adults in Brazil.
AB  - Despite a high prevalence of sexually transmitted Chlamydia trachomatis
      infections in Brazil and other countries in South America, very little is known
      about the distribution of C. trachomatis genovars. In this study, we genotyped C.
      trachomatis strains from urine or endocervical specimens collected from 163 C.
      trachomatis-positive female and male youths, and female adults, residing in two
      different regions of Brazil, the city of Goiania located in the central part of
      Brazil, and the city of Vitoria in the south-east region. C. trachomatis strains
      were genotyped by amplifying and sequencing the ompA gene encoding the chlamydial
      major outer-membrane protein, which is genovar specific. We found nine different
      C. trachomatis genovars: E (39.3%), F (16.6%), D (15.9%), I (8.6%), J (7.4%), G
      (4.9%), K (3.1%), H (2.4%) and B (1.8%). The distribution of the C. trachomatis
      genovars in the two regions of Brazil was similar, and there was no statistically
      significant association of serovars with age, gender, number of sexual partners
      or clinical symptoms. The overall distribution of C. trachomatis genovars in
      Brazil appears similar to that found in other regions of the world, where E, D
      and F are the most common. This supports the notion that, during the last few
      decades, the overall distribution of C. trachomatis genovars throughout the world
      has been relatively stable.

PMID- 21183599
TI  - Detection and species identification of microsporidial infections using SYBR
      Green real-time PCR.
AB  - Diagnosis of microsporidial infections is routinely performed by light
      microscopy, with unequivocal non-molecular species identification achievable only
      through electron microscopy. This study describes a single SYBR Green real-time
      PCR assay for the simultaneous detection and species identification of such
      infections. This assay was highly sensitive, routinely detecting infections
      containing 400 parasites (g stool sample)(-1), whilst species identification was
      achieved by differential melt curves on a Corbett Life Science Rotor-Gene 3000. A
      modification of the QIAamp DNA tissue extraction protocol allowed the semi
      automated extraction of DNA from stools for the routine diagnosis of
      microsporidial infection by real-time PCR. Of 168 stool samples routinely
      analysed for microsporidian spores, only five were positive by microscopy. By
      comparison, 17 were positive for microsporidial DNA by real-time analysis,
      comprising 14 Enterocytozoon bieneusi, one Encephalitozoon cuniculi and two
      separate Pleistophora species infections.

PMID- 21183600
TI  - Rapid and accurate identification of species belonging to the Candida
      parapsilosis complex by real-time PCR and melting curve analysis.
AB  - Candida parapsilosis is the second most frequent Candida species isolated from
      blood cultures. Since 2005, C. parapsilosis has been divided into three distinct
      species based on genetic traits: Candida parapsilosis, Candida metapsilosis and
      Candida orthopsilosis. The aim of this study was to develop a rapid real-time PCR
      assay able to distinguish these closely related species via a melting curve
      analysis. This identification method was optimized by using reference strains and
      well-characterized clinical isolates of Candida species. A single set of
      consensus primers was designed to amplify a 184 bp portion of the SADH gene in
      order to identify species based on the unique melt profile resulting from DNA
      sequence variations from each species of the complex. PCR products were detected
      with SYBR Green fluorescent dye and identification was established by melting
      curve analysis. For validation of the technique, a total of 116 clinical
      isolates, phenotypically identified as C. parapsilosis, were tested by real-time
      PCR and results were further compared with PCR-RFLP patterns of the SADH gene,
      used as the reference method. The melting curve analysis of amplified DNA could
      differentiate between C. parapsilosis (83.5  degrees C), C. metapsilosis (82.9 
      degrees C) and C. orthopsilosis (82.1  degrees C), with a sensitivity and
      specificity comparable to those of the reference method. One hundred and fourteen
      C. parapsilosis and two C. orthopsilosis isolates were identified among the
      clinical isolates. This method provides a simple, rapid and reliable
      identification of species belonging to the C. parapsilosis complex. This novel
      approach could be helpful for clinical and epidemiological investigations.

PMID- 21183601
TI  - Clinical presentation and molecular characterization of group B rotaviruses in
      diarrhoea patients in Bangladesh.
AB  - A total of 1106 stool samples collected from diarrhoea patients admitted to Dhaka
      hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh,
      during January-December 2008 were analysed for the presence of rotavirus-specific
      RNA by PAGE. The group B-specific RNA migration pattern was detected in 26
      patients (2.4%) and group A-specific pattern in 259 patients (23.4%). Clinical
      data from group A and group B rotavirus-infected patients indicated that episodes
      did not differ much in the prevalence of diarrhoea, number of stools, outcome or
      differences in gender. However, abdominal pain was more common in group B
      rotavirus infections (36 vs 15%, P=0.02) and the virus was responsible for more
      severe dehydration compared with group A-infected patients (12 vs 3%, P=0.04).
      Sequence analyses of VP4, VP7 and NSP2 indicated that an Indian-Bangladeshi
      lineage of the virus, which is different from both the prototype (Chinese)
      lineage and from the animal group B rotaviruses, has been circulating in
      Bangladesh. Continuous monitoring of group B rotaviruses both in hospitals and in
      the community will be helpful to determine the true burden of group B
      rotaviruses.

PMID- 21183602
TI  - Extended-spectrum beta-lactamase-producing Gram-negative bacteria causing
      neonatal sepsis in India in rural and urban settings.
AB  - Extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacilli (GNB) are
      of increasing clinical concern in all age groups worldwide. Whilst sepsis
      continues to be the leading cause of morbidity and mortality in Indian neonates
      in the community, identification of microbiological attributes in this population
      is lacking. This population-based study enrolled 1738 infants with a diagnosis of
      clinical sepsis at four participating centres in India. Each study site conducted
      Bactec blood culture, identified bacterial species by API test and stored
      isolates at -70  degrees C. From 252 GNB isolates, 155 (113 Klebsiella species,
      21 Escherichia coli and 21 other) were subjected to drug susceptibility testing,
      ESBL phenotyping and testing for clonal relatedness of ESBL strains by PFGE. The
      results demonstrated that Klebsiella species and E. coli are the most common GNB
      causes of neonatal sepsis in India, and over one-third are ESBL producers in both
      community and hospital settings. ESBL-producing strains exhibited frequent co
      resistance to aminoglycosides and ciprofloxacin, but remained susceptible to
      imipenem. PFGE analysis revealed extensive genetic diversity within the ESBL
      producing isolates, showing multiple profiles (total of 23). Over 40% of all ESBL
      producing isolates formed three pulsed-field profiles (PFP I-III), with PFP-II
      being the largest cluster (>20% of all ESBL-producing isolates), sharing strains
      from two distant locations. Identification of a common clone at two
      geographically distant centres indicated that predominant clones with increased
      virulence may exist, even in the absence of any clear outbreak. The presence of
      ESBL-producing strains in community infants with no prior history of
      hospitalization or antibiotic use dictates heightened vigilance and further
      studies on the ecology of these organisms.

PMID- 21183603
TI  - Detection of Candida albicans DNA from blood samples using a novel
      electrochemical assay.
AB  - The genus Candida contains a number of yeast species which are opportunistic
      pathogens and are associated with life-threatening infections in
      immunocompromised individuals. Provision of appropriate therapy relies on the
      rapid identification of the infecting species, and existing methods of
      identifying Candida species in clinical samples are time and resource intensive
      and are not always specific enough to differentiate between drug-susceptible and
      drug-resistant species. We have previously developed a system for the rapid
      detection of yeast pathogens in clinical samples using PCR followed by
      hybridization with a suite of five species-specific, electrochemically labelled
      DNA probes. The limit of detection of the assay was shown to be 37 fg (~1 genome)
      per reaction using extracted genomic DNA. We carried out a study to test the
      limit of detection of one of the probes, CA PR3, using blood samples from a
      healthy donor that were spiked with genomic DNA or with C. albicans cells. Our
      results demonstrated a limit of detection of 37 fg (ml blood)(-1) (~1 genome ml(
      1)) using extracted DNA or 10 c.f.u. (ml blood)(-1) using C. albicans cells,
      indicating that the assay is capable of detecting C. albicans nucleic acid at
      levels that are encountered in clinical samples.

PMID- 21183604
TI  - A case of pulmonary aspergilloma and actinomycosis.
AB  - Pulmonary aspergilloma and pulmonary actinomycosis are rare pulmonary infectious
      diseases. Clinical manifestations of pulmonary aspergilloma and pulmonary
      actinomycosis include chronic cough, fever, chest pain, haemoptysis and other
      pathologies, but some patients may be asymptomatic. We report a case of a healthy
      33-year-old woman without any underlying diseases, who was admitted to Zhongxing
      Branch of Taipei City Hospital, Taiwan, for intermittent haemoptysis and right
      upper chest pain, which had persisted for several months. A chest radiograph
      revealed a focal consolidation in the right upper lobe (RUL) of the lung, which
      grew in size over time. A sputum study and bronchoscopy revealed no positive
      findings, although malignancy could not be ruled out. Thus, the patient received
      a wedge resection of the RUL lesion. Subsequent, pathological examination
      demonstrated the presence of pulmonary aspergilloma and pulmonary actinomycosis.
      The patient's symptoms resolved after resection of the RUL lesion.

PMID- 21183605
TI  - The neuropsychological course of acute delirium in adult hematopoietic stem cell
      transplantation patients.
AB  - Although delirium is a common medical comorbidity with altered cognition as its
      defining feature, few publications have addressed the neuropsychological
      prodrome, profile, and recovery of patients tested during delirium. We
      characterize neuropsychological performance in 54 hemapoietic stem cell/bone
      marrow transplantation (BMT) patients shortly before, during, and after delirium
      and in BMT patients without delirium and 10 healthy adults. Patients were
      assessed prospectively before and after transplantation using a brief battery.
      BMT patients with delirium performed more poorly than comparisons and those
      without delirium on cross-sectional and trend analyses. Deficits were in expected
      areas of attention and memory, but also in psychomotor speed and learning. The
      patients with delirium did not return to normative "average" on any test during
      observation. Most tests showed a mild decline in the visit before delirium, a
      sharp decline with delirium onset, and variable performance in the following
      days. This study adds to the few investigations of neuropsychological performance
      surrounding delirium and provides targets for monitoring and early detection;
      Trails A and B, RBANS Coding, and List Recall may be useful for delirium
      assessment.

PMID- 21183606
TI  - Loss of JNK2 increases intestinal tumor susceptibility in Apc1638+/- mice with
      dietary modulation.
AB  - A recent study has shown that c-Jun NH2-terminal kinases (JNKs) 2 interacts with
      and inhibits beta-catenin signaling in vitro. To determine the role of genetic
      interaction between JNK2 and beta-catenin in vivo and to elucidate JNK2-mediated
      intestinal carcinogenesis, we crossed the JNK2-/- mice with Apc1638+/- mice that
      carry inactivated Apc allele and develop intestinal tumor due to beta-catenin
      activation. We found that the introduction of mutant JNK2 into Apc1638+/- mice
      did not increase intestinal tumorigenesis when the mice were fed a defined AIN
      76A control diet. However, loss of JNK2 significantly increased animal body
      weight in the Apc/JNK2+/- and Apc/JNK2-/- mice. Surprisingly, JNK2 loss was
      synergistic with a Western-style high-risk diet (high fat and phosphate and low
      calcium and vitamin D) to accelerate intestinal tumorigenesis. Tumor number
      increased to 3.56 from 1.89 (on AIN-76A diet) in the Apc/JNK2+/- mice (P<0.01)
      and increased to 4.14 from 1.92 (on AIN-76A diet) in the Apc/JNK2-/- mice
      (P<0.01) although there was a slight increase of tumor formation in Apc/JNK2+/+
      mice. Intestinal tumorigenesis in Apc/JNK2 double-mutant mice with high-risk diet
      modulation was associated with beta-catenin signaling, peroxisome proliferator
      activated receptor-gamma and inflammation pathway. Collectively, we concluded
      that JNK2 may function in controlling fat metabolism and loss of JNK2 increases
      the risk of obesity, the latter synergizes with high-fat diet to increase
      intestinal tumor susceptibility. This data strongly suggests the importance of
      JNK2 in intestinal carcinogenesis and the importance of dietary manipulation for
      cancer prevention in the population whose JNK2 is inactivated.

PMID- 21183609
TI  - Overdiagnosing subjects with COPD using the 0.7 fixed ratio: correlation with a
      poor health-related quality of life.
AB  - BACKGROUND: The current debate about the lower limit of normal (LLN) vs the 0.7
      fixed ratio to diagnose COPD is not completely resolved, and little information
      about the clinical impact of these different criteria is available. We compared
      differences in health-related quality of life, exacerbations, exercise tolerance,
      physical activity, comorbidity, and systemic biomarkers of subjects with
      FEV(1)/FVC < 0.7 but > LLN (ratio-only group) vs subjects without COPD and those
      with mild or moderate to severe COPD. METHODS: A population-based sample of 3,802
      subjects aged 40 to 80 years from the Epidemiologic Study of COPD in Spain was
      selected. Subjects were evaluated with postbronchodilator spirometry, quality-of
      life and physical activity questionnaires, and 6-min walk tests. Exacerbations
      within the previous year and comorbidities were recorded. Systemic biomarkers
      were measured after excluding subjects with conditions associated with systemic
      inflammatory processes. RESULTS: Fixed-ratio COPD overdiagnosis affects up to
      4.6% of subjects aged 40 to 80 years, is more frequent in men, and increases with
      age. After adjusting for confounding factors, the ratio-only group had a worse
      health-related quality of life than the non-COPD group, with poorer scores in all
      questionnaire domains (P < .05). However, no differences between the two groups
      for respiratory exacerbations, 6-min walk distance, physical activity, or
      systemic biomarkers were observed. Ratio-only subjects did not present greater
      risk for cardiovascular disease (adjusted relative OR, 1.47; 95% CI, 0.81-2.64),
      whereas subjects with mild COPD did (adjusted relative OR, 2.32; 95% CI, 1.11
      4.84). CONCLUSIONS: Subjects receiving a diagnosis of COPD by the fixed ratio
      present worse self-reported quality of life than subjects without COPD but had
      similar exercise, frequency of exacerbations, and indices of systemic effects.

PMID- 21183608
TI  - Microsomal epoxide hydroxylase genotypes/diplotypes, traffic air pollution, and
      childhood asthma.
AB  - BACKGROUND: Epidemiologic studies indicate that exposure to air pollution caused
      by traffic may have an association with an increased risk of childhood asthma.
      Some studies report an association between the polymorphisms of the microsomal
      epoxide hydroxylase (EPHX1) gene and enzyme activity. We investigated the
      associations of EPHX1 Tyr113His and His139Arg polymorphisms with asthma and
      wheezing outcomes, and focused on the functional genetic change in different
      ambient nitrogen dioxide (NO2) levels on glutathione S-transferase p1 (GSTP1) and
      glutathione S-transferase m1 (GSTM1) genotypes. METHODS: A total of 3,741
      children were enrolled in the Taiwan Children Health Study from 14 communities.
      We examined the associations of EPHX1 Tyr113His and His139Arg genotypes and
      diplotypes with asthma and wheezing outcomes under different ambient NO2
      exposures. RESULTS: Children with the EPHX1 Arg/His or Arg/Arg genotypes at codon
      139 were significantly associated with increased risks of lifetime asthma
      (adjusted OR [aOR] = 1.3; 95% CI, 1.1-1.7; and aOR = 1.5; 95% CI, 1.1-2.1,
      respectively). The EPHX1 diplotypes showed significant associations with lifetime
      asthma (global P value = .01) and early-onset asthma (global P value = .01). The
      risk of EPHX1 139Arg allele and 113Tyr-139Arg diplotype were of greater magnitude
      in higher compared with lower NO2 communities. The increase of the effect from
      the EPHX1 139Arg allele with higher NO2 exposure was most marked in the GSTP1 Val
      allele and GSTM1 present genotype. CONCLUSIONS: Children with high EPHX1 activity
      may have increase risk of asthma and wheezing outcomes, and can be mediated
      through airway oxidative stress generation.

PMID- 21183607
TI  - Reptiles and mammals have differentially retained long conserved noncoding
      sequences from the amniote ancestor.
AB  - Many noncoding regions of genomes appear to be essential to genome function.
      Conservation of large numbers of noncoding sequences has been reported repeatedly
      among mammals but not thus far among birds and reptiles. By searching genomes of
      chicken (Gallus gallus), zebra finch (Taeniopygia guttata), and green anole
      (Anolis carolinensis), we quantified the conservation among birds and reptiles
      and across amniotes of long, conserved noncoding sequences (LCNS), which we
      define as sequences >=500 bp in length and exhibiting >=95% similarity between
      species. We found 4,294 LCNS shared between chicken and zebra finch and 574 LCNS
      shared by the two birds and Anolis. The percent of genomes comprised by LCNS in
      the two birds (0.0024%) is notably higher than the percent in mammals (<0.0003%
      to <0.001%), differences that we show may be explained in part by differences in
      genome-wide substitution rates. We reconstruct a large number of LCNS for the
      amniote ancestor (ca. 8,630) and hypothesize differential loss and substantial
      turnover of these sites in descendent lineages. By contrast, we estimated a small
      role for recruitment of LCNS via acquisition of novel functions over time. Across
      amniotes, LCNS are significantly enriched with transcription factor binding sites
      for many developmental genes, and 2.9% of LCNS shared between the two birds show
      evidence of expression in brain expressed sequence tag databases. These results
      show that the rate of retention of LCNS from the amniote ancestor differs between
      mammals and Reptilia (including birds) and that this may reflect differing roles
      and constraints in gene regulation.

PMID- 21183611
TI  - Decreased fraction of exhaled nitric oxide in obese subjects with asthma
      symptoms: data from the population study INTERGENE/ADONIX.
AB  - BACKGROUND: Several studies have demonstrated an association between obesity and
      asthma. However, it is uncertain if fraction of exhaled nitric oxide (Feno),
      which is used as a marker of airway inflammation, and atopy are associated with
      BMI. The aim of this study was to examine if obese subjects with asthma symptoms
      have a different phenotype of asthma than nonobese subjects as indicated by Feno.
      METHODS: The subjects (N = 2,187) consisted of women and men, aged 25 to 74,
      living in Gothenburg, Sweden, who participated in the randomly selected INTERGENE
      study cohort. Measurements included anthropometric measures, bioelectric
      impedance, Feno, pulmonary function, and blood samples for IgE; questionnaires
      included items on respiratory symptoms. Obesity was defined as BMI >= 30 kg/m(2).
      In this cross-sectional analysis, general linear models were used to analyze how
      Feno was associated with anthropometry, body composition, wheezing, and atopy.
      RESULTS: In nonobese subjects, wheezing was associated with raised Feno and
      atopy, whereas in contrast, obese subjects who reported wheezing had lower Feno
      than obese subjects without wheezing (16.1 vs 19.1 parts per billion, P < .01).
      The prevalence of atopy was similar in both of those subgroups (25.0% vs 20.7%, P
      = .4). Similarly, in 395 subjects (19%) who reported wheezing, Feno was
      negatively associated with BMI, waist-to-hip ratio, and percentage of body fat,
      whereas no significant relationships were observed in those without respiratory
      symptoms. CONCLUSIONS: Wheezing was significantly associated with reduced Feno in
      obese subjects, whereas there was a positive association between wheezing and
      Feno among the nonobese subjects, indicating a possible difference in asthma
      phenotype, based on body weight.

PMID- 21183610
TI  - Descriptors of breathlessness in children with persistent asthma.
AB  - BACKGROUND: In adult patients, the consistent use of language to describe dyspnea
      enhances patient-provider communication and contributes to diagnostic and
      therapeutic decisions. The objective of this research was to determine whether
      pediatric patients similarly display consistency in the language used to describe
      "uncomfortable awareness of breathing." METHODS: One hundred children between the
      ages of 8 and 15 years with moderate to severe persistent asthma enrolled in an
      asthma education research program completed questionnaires regarding descriptors
      of asthma on each of two occasions. In addition to the breathlessness
      questionnaires, demographic information, self-reported asthma severity, ED
      visits, missed school days, anthropometrics, and spirometry were obtained for
      each participant. RESULTS: Children were reliable in their choice of the
      descriptors that they applied to their breathing discomfort across two occasions,
      and they selected the same descriptors that were used by adults with asthma in
      previous studies. Children with greater self-reported asthma severity endorsed
      more descriptors to characterize breathing discomfort than did children with less
      severe asthma, but no differences were found among children based on demographic
      or anthropometric variables. CONCLUSIONS: Children with moderate to severe
      persistent asthma are reliable in their choice of descriptors of breathlessness.
      Knowledge of their experience of symptoms may be helpful clinically in the
      assessment and management of asthma.

PMID- 21183612
TI  - Defining the origins of the NOD-like receptor system at the base of animal
      evolution.
AB  - Distinguishing self from nonself and the onset of defense effector mechanisms
      upon recognition of pathogens are essential for the survival of all life forms in
      the animal kingdom. The family of nucleotide -binding and oligomeriszation domain
      like receptors (NLRs) was first identified in vertebrates and comprises a group
      of pivotal sensor protein of the innate immune system for microbial cell wall
      components or danger signals. Here, we provide first evidence that early
      diverging metazoans have large and complex NLR repertoires. The cnidarian
      NACHT/NB-ARC genes include novel combinations of domains, and the number of one
      specific type (NB-ARC and tetratricopeptide repeat containing) in Hydra is
      particularly large. We characterize the transcript structure and expression
      patterns of a selected HyNLR, HyNLR type 1 and describe putative interaction
      partners. In a heterologous expression system, we show induced proximity
      recruitment of an effector caspase (HyDD-Caspase) to the HyNLR type 1 protein
      upon oligomerization indicating a potential role of caspase activation downstream
      of NLR activation in Hydra. These results add substantially to our understanding
      of the ancestral innate immune repertoire as well as providing the first insights
      into putative cytoplasmic defense mechanisms at the base of animal evolution.

PMID- 21183613
TI  - Cheetah paradigm revisited: MHC diversity in the world's largest free-ranging
      population.
AB  - For more than two decades, the cheetah (Acinonyx jubatus) has been considered a
      paradigm of disease vulnerability associated with low genetic diversity,
      particularly at the immune genes of the major histocompatibility complex (MHC).
      Cheetahs have been used as a classic example in numerous conservation genetics
      textbooks as well as in many related scientific publications. However, earlier
      studies used methods with low resolution to quantify MHC diversity and/or small
      sample sizes. Furthermore, high disease susceptibility was reported only for
      captive cheetahs, whereas free-ranging cheetahs show no signs of infectious
      diseases and a good general health status. We examined whether the diversity at
      MHC class I and class II-DRB loci in 149 Namibian cheetahs was higher than
      previously reported using single-strand conformation polymorphism analysis,
      cloning, and sequencing. MHC genes were examined at the genomic and
      transcriptomic levels. We detected ten MHC class I and four class II-DRB alleles,
      of which nine MHC class I and all class II-DRB alleles were expressed.
      Phylogenetic analyses and individual genotypes suggested that the alleles belong
      to four MHC class I and three class II-DRB putative loci. Evidence of positive
      selection was detected in both MHC loci. Our study indicated that the low number
      of MHC class I alleles previously observed in cheetahs was due to a smaller
      sample size examined. On the other hand, the low number of MHC class II-DRB
      alleles previously observed in cheetahs was further confirmed. Compared with
      other mammalian species including felids, cheetahs showed low levels of MHC
      diversity, but this does not seem to influence the immunocompetence of free
      ranging cheetahs in Namibia and contradicts the previous conclusion that the
      cheetah is a paradigm species of disease vulnerability.

PMID- 21183614
TI  - Patient-specific computational hemodynamics of intracranial aneurysms from 3D
      rotational angiography and CT angiography: an in vivo reproducibility study.
AB  - BACKGROUND AND PURPOSE: Patient-specific simulations of the hemodynamics in
      intracranial aneurysms can be constructed by using image-based vascular models
      and CFD techniques. This work evaluates the impact of the choice of imaging
      technique on these simulations. MATERIALS AND METHODS: Ten aneurysms, imaged with
      3DRA and CTA, were analyzed to assess the reproducibility of geometric and
      hemodynamic variables across the 2 modalities. RESULTS: Compared with 3DRA
      models, we found that CTA models often had larger aneurysm necks (P = .05) and
      that most of the smallest vessels (between 0.7 and 1.0 mm in diameter) could not
      be reconstructed successfully with CTA. With respect to the values measured in
      the 3DRA models, the flow rate differed by 14.1 +/- 2.8% (mean +/- SE) just
      proximal to the aneurysm and 33.9 +/- 7.6% at the aneurysm neck. The mean WSS on
      the aneurysm differed by 44.2 +/- 6.0%. Even when normalized to the parent vessel
      WSS, a difference of 31.4 +/- 9.9% remained, with the normalized WSS in most
      cases being larger in the CTA model (P = .04). Despite these substantial
      differences, excellent agreement (kappa >= 0.9) was found for qualitative
      variables that describe the flow field, such as the structure of the flow pattern
      and the flow complexity. CONCLUSIONS: Although relatively large differences were
      found for all evaluated quantitative hemodynamic variables, the main flow
      characteristics were reproduced across imaging modalities.

PMID- 21183615
TI  - MR imaging of optic neuropathy with extended echo-train acquisition fluid
      attenuated inversion recovery.
AB  - BACKGROUND AND PURPOSE: XETA, also known as Cube, is a relatively new 3D FSE
      sequence that can be used to perform whole-brain FLAIR T2-weighted imaging at
      isotropic high spatial resolution. This high-resolution volumetric imaging,
      coupled with both fat and fluid suppression, permits ideal evaluation of optic
      nerve anatomy and signal intensity; therefore, we hypothesized that XETA FLAIR
      would be useful for the detection of T2 signal-intensity abnormality in the optic
      nerve. Our purpose was to evaluate the sensitivity of XETA FLAIR for this
      abnormality and to compare it with the coronal FSE T2 FS. MATERIALS AND METHODS:
      After obtaining approval of the institutional review board, 2 CAQ
      neuroradiologists retrospectively reviewed all patients with a clinical diagnosis
      of optic neuropathy who had undergone XETA FLAIR and standard orbital imaging
      from September 2006 to February 2009. Fifteen patients met these criteria and
      underwent the following sequences: XETA FLAIR, coronal FSE T2 FS, and T1-weighted
      postgadolinium sequences with FS. RESULTS: Signal-intensity abnormality was
      identified on the correct side of the patient's vision loss in all 15 patients on
      XETA but in only 11/15 patients on the coronal FSE T2-weighted imaging. Reviewer
      1 perceived the signal-intensity abnormality better on the XETA versus T2
      weighted imaging in 10/15 patients, and reviewer 2, in 9/15 patients. Neither
      reviewer visualized any of the imaging better by using the conventional coronal
      FSE T2 FS sequence. CONCLUSIONS: XETA FLAIR was more sensitive than coronal FSE
      T2 FS for identifying abnormal signal intensity within the optic nerves in
      patients with optic neuropathy.

PMID- 21183616
TI  - Corpus callosum length by gestational age as evaluated by fetal MR imaging.
AB  - Although suspected corpus callosum abnormality is a common indication for fetal
      MR imaging, biometric data specific to MR imaging are sparse. We sought to
      characterize growth in corpus callosum length by EGA with fetal MR imaging.
      Corpus callosum segments were assessed and overall corpus callosum length was
      measured and plotted against the EGA for 68 anatomically normal fetal brains
      ranging in EGA from 18.5 to 37.7 weeks, and linear and polynomial regression
      models were calculated. The body of the corpus callosum was identified in all
      fetuses, followed in frequency by the splenium (91.2%), genu (85.3%), and rostrum
      (32.4%). Measurements of corpus callosum length by MR imaging were in agreement
      with values established by sonography. A second-degree polynomial function was
      the best fit for callosal length by EGA. Understanding this normal growth pattern
      may enhance detection of subtle growth abnormalities.

PMID- 21183618
TI  - Functional MR imaging evidence of altered functional activation in metabolic
      syndrome.
AB  - BACKGROUND AND PURPOSE: MetS is a cluster of risk factors associated with
      significant cardiovascular morbidity and mortality and diminished cognitive
      function. Given that little is known about the early signs of brain vulnerability
      related to persistent metabolic dysfunction, we set out to determine whether
      cognitively healthy middle-aged individuals with MetS exhibit an altered
      cerebrovascular response to a cognitive challenge relative to those without MetS.
      MATERIALS AND METHODS: Forty neurologically healthy adults aged 40-60 years (19
      with MetS and 21 healthy controls) performed a 2-back verbal working memory task
      during fMRI. We compared BOLD responses between the 2 groups in 8 a priori
      regions of interest previously shown to be associated with the 2-back in patients
      with cardiovascular disease. RESULTS: Age, education level, sex distribution,
      cognitive and emotional functioning, and task performance (accuracy and reaction
      time) were not different between the groups. Compared with healthy controls,
      individuals with MetS demonstrated a lower 2-back-related BOLD response in the
      right superior frontal gyrus, right superior parietal lobule, and left inferior
      parietal lobule. CONCLUSIONS: This study provides preliminary evidence that
      cognitively intact middle-aged individuals with MetS exhibit significant
      alterations in cerebrovascular response to a cognitive challenge. Our results
      also demonstrate that fMRI may identify early brain changes associated with MetS.

PMID- 21183617
TI  - Aberrant diffusion and geometric properties in the left arcuate fasciculus of
      developmentally delayed children: a diffusion tensor imaging study.
AB  - BACKGROUND AND PURPOSE: One of the neurologic substrates of poor language in
      children with DD is the abnormal development of perisylvian language networks. We
      sought to determine whether this manifests as aberrant regional changes in
      diffusivity or geometry of the left AF. MATERIALS AND METHODS: We performed DTI
      studies in 16 young (age, 55.4 +/- 18.95 months) patients with DD and 11 age- and
      sex-matched TD children (age, 60.09 +/- 21.27 months). All children were right
      handed. To detect the malformation of left AF structure in native or standard
      space, we proposed new methodology consisting of 2 complementary approaches,
      principal fiber orientation quantification in color-coded anisotropic maps and
      tract-based morphometry analysis. RESULTS: Patients with DD did not show the
      typical pattern of age-related maturity of the AP and ML pathways passing through
      the left AF (R(2) of the AP pathway: DD versus TD = 0.002 versus 0.4542; R(2) of
      the ML pathway: DD versus TD = 0.002 versus 0.4154). In addition, the patients
      with DD showed significantly reduced FA in the temporal portion of the AF (mean
      FA of DD versus TD = 0.37 +/- 0.11 versus 0.48 +/- 0.06, P < .001), and the AF
      showed higher curvatures in the parietotemporal junction, resulting in sharper
      bends to the Wernicke area (mean curvature of DD versus TD = 0.12 +/- 0.03 versus
      0.06 +/- 0.02, P < .001). CONCLUSIONS: The proposed methods successfully revealed
      regional abnormalities in the axonal integrity of the left AF in the patients
      with DD. These abnormalities support the notion that the perisylvian language
      network is malformed in children with DD.

PMID- 21183620
TI  - Scaling back on scales with a scale of scales.

PMID- 21183619
TI  - Using high-resolution MR imaging at 7T to evaluate the anatomy of the midbrain
      dopaminergic system.
AB  - BACKGROUND AND PURPOSE: Dysfunction of DA neurotransmission from the SN and VTA
      has been implicated in neuropsychiatric diseases, including Parkinson disease and
      schizophrenia. Unfortunately, these midbrain DA structures are difficult to
      define on clinical MR imaging. To more precisely evaluate the anatomic
      architecture of the DA midbrain, we scanned healthy participants with a 7T MR
      imaging system. Here we contrast the performance of high-resolution T2- and T2*
      weighted GRASE and FFE MR imaging scans at 7T. MATERIALS AND METHODS: Ten healthy
      participants were scanned by using GRASE and FFE sequences. CNRs were calculated
      among the SN, VTA, and RN, and their volumes were estimated by using a
      segmentation algorithm. RESULTS: Both GRASE and FFE scans revealed visible
      contrast between midbrain DA regions. The GRASE scan showed higher CNRs compared
      with the FFE scan. The T2* contrast of the FFE scan further delineated
      substructures and microvasculature within the midbrain SN and RN. Segmentation
      and volume estimation of the midbrain SN, RN, and VTA showed individual
      differences in the size and volume of these structures across participants.
      CONCLUSIONS: Both GRASE and FFE provide sufficient CNR to evaluate the anatomy of
      the midbrain DA system. The FFE in particular reveals vascular details and
      substructure information within the midbrain regions that could be useful for
      examining structural changes in midbrain pathologies.

PMID- 21183622
TI  - Complex systems in pulmonary medicine: a systems biology approach to lung
      disease.
AB  - The lung is a highly complex organ that can only be understood by integrating the
      many aspects of its structure and function into a comprehensive view. Such a view
      is provided by a systems biology approach, whereby the many layers of complexity,
      from the molecular genetic, to the cellular, to the tissue, to the whole organ,
      and finally to the whole body, are synthesized into a working model of
      understanding. The systems biology approach therefore relies on the expertise of
      many disciplines, including genomics, proteomics, metabolomics, physiomics, and,
      ultimately, clinical medicine. The overall structure and functioning of the lung
      cannot be predicted from studying any one of these systems in isolation, and so
      this approach highlights the importance of emergence as the fundamental feature
      of systems biology. In this paper, we will provide an overview of a systems
      biology approach to lung disease by briefly reviewing the advances made at many
      of these levels, with special emphasis on recent work done in the realm of
      pulmonary physiology and the analysis of clinical phenotypes.

PMID- 21183621
TI  - Protein microarrays discover angiotensinogen and PRKRIP1 as novel targets for
      autoantibodies in chronic renal disease.
AB  - Biomarkers for early detection of chronic kidney disease are needed, as millions
      of patients suffer from chronic diseases predisposing them to kidney failure.
      Protein microarrays may also hold utility in the discovery of auto-antibodies in
      other conditions not commonly considered auto-immune diseases. We hypothesized
      that proteins are released as a consequence of damage at a cellular level during
      end-organ damage from renal injury, not otherwise recognized as self-antigens,
      and an adaptive humoral immune response to these proteins might be detected in
      the blood, as a noninvasive tracker of this injury. The resultant antibodies (Ab)
      detected in the blood would serve as effective biomarkers for occult renal
      injury, enabling earlier clinical detection of chronic kidney disease than
      currently possible, because of the redundancy of the serum creatinine as a
      biomarker for early kidney injury. To screen for novel autoantibodies in chronic
      kidney disease, 24 protein microarrays were used to compare serum Ab from
      patients with chronic kidney disease against matched controls. From a panel of 38
      antigens with increased Ab binding, four were validated in 71 individuals, with
      (n=50) and without (n=21) renal insufficiency. Significant elevations in the
      titer of novel auto-Ab were noted against angiotensinogen and PRKRIP1 in renal
      insufficiency. Current validation is underway to evaluate if these auto-Ab can
      provide means to follow the evolution of chronic kidney disease in patients with
      early stages of renal insufficiency, and if these rising titers of these auto-Ab
      correlate with the rate of progression of chronic kidney disease.

PMID- 21183623
TI  - Endothelin-1 attenuates increases in hydraulic conductivity due to platelet
      activating factor via prostacyclin release.
AB  - We previously showed that endothelin-1 (ET-1) and prostacyclin (PGI(2)) similarly
      attenuate increases in microvascular permeability induced by platelet-activating
      factor (PAF). This led us to hypothesize that ET-1 attenuates trans-endothelial
      fluid flux during PAF through PGI(2) release. We tested this hypothesis in three
      phases. First, bovine pulmonary artery endothelial cells were exposed to 0.008-8
      MUM ET-1 and assayed for PGI(2) release. Second, to determine whether increased
      transmonolayer flux after PAF could be attenuated by ET-1 or PGI(2) and reversed
      by PGI(2) synthesis inhibition or PGI(2) receptor blockade, we measured
      endothelial cell transmonolayer flux after cells were exposed to 10 nM PAF plus
      10 MUM PGI(2) or 80 pM ET-1, with or without 500 MUM tranylcypromine (PGI(2)
      synthase inhibitor) or 20 MUM CAY-10441 (PGI(2) receptor blocker). Finally,
      hydraulic conductivity (L(p)) was measured in rat mesenteric venules in vivo
      after exposure to 10 nM PAF and 80 pM ET-1 with or without tranylcypromine (100
      and 500 MUM) or CAY-10441 (2 and 20 MUM). We found that in vitro, ET-1 stimulated
      a dose-dependent increase in PGI(2) production (from 126 to 217 pg/ml, P < 0.01).
      Compared with PAF alone, PGI(2) plus PAF and ET-1 plus PAF decreased
      transmonolayer flux similarly by 52 and 46%, respectively (P < 0.01), while
      tranylcypromine and CAY-10441 reversed these effects by 92 and 47%, respectively
      (P < 0.05). In vivo, PAF increased L(p) fourfold (P < 0.01) and ET-1 attenuated
      this effect by 83% (P < 0.01). Tranylcypromine and CAY-10441 reversed the ET-1
      attenuation in L(p) during PAF by 55 and 45%, respectively (P < 0.01). We
      conclude that ET-1 may stimulate endothelial cell PGI(2) release to attenuate the
      increases in transmonolayer flux and hydraulic conductivity secondary to PAF.

PMID- 21183624
TI  - A toast to health and performance! Beetroot juice lowers blood pressure and the
      O2 cost of exercise.

PMID- 21183625
TI  - Effects of inhaled nitric oxide at rest and during exercise in idiopathic
      pulmonary fibrosis.
AB  - Patients with idiopathic pulmonary fibrosis (IPF) usually develop hypoxemia and
      pulmonary hypertension when exercising. To what extent endothelium-derived
      vasodilating agents modify these changes is unknown. The study was aimed to
      investigate in patients with IPF whether exercise induces changes in plasma
      levels of endothelium-derived signaling mediators, and to assess the acute
      effects of inhaled nitric oxide (NO) on pulmonary hemodynamics and gas exchange,
      at rest and during exercise. We evaluated seven patients with IPF (6 men/1 woman;
      57 +/- 11 yr; forced vital capacity, 60 +/- 13% predicted; carbon monoxide
      diffusing capacity, 52 +/- 10% predicted). Levels of endothelin, 6-keto
      prostaglandin-F(1alpha), thromboxane B(2), and nitrates were measured at rest and
      during submaximal exercise. Pulmonary hemodynamics and gas exchange, including
      ventilation-perfusion relationships, were assessed breathing ambient air and 40
      ppm NO, both at rest and during submaximal exercise. The concentration of
      thromboxane B(2) increased during exercise (P = 0.046), whereas levels of other
      mediators did not change. The change in 6-keto-prostaglandin-F(1alpha) correlated
      with that of mean pulmonary arterial pressure (r = 0.94; P < 0.005). Inhaled NO
      reduced mean pulmonary arterial pressure at rest (-4.6 +/- 2.1 mmHg) and during
      exercise (-11.7 +/- 7.1 mmHg) (P = 0.001 and P = 0.004, respectively), without
      altering arterial oxygenation or ventilation-perfusion distributions in any of
      the study conditions. Alveolar-to-capillary oxygen diffusion limitation, which
      accounted for the decrease of arterial Po(2) during exercise, was not modified by
      NO administration. We conclude that, in IPF, some endothelium-derived signaling
      molecules may modulate the development of pulmonary hypertension during exercise,
      and that the administration of inhaled NO reduces pulmonary vascular resistance
      without disturbing gas exchange.

PMID- 21183626
TI  - An anatomical and functional model of the human tracheobronchial tree.
AB  - The human tracheobronchial tree is a complex branched distribution system in
      charge of renewing the air inside the acini, which are the gas exchange units. We
      present here a systematic geometrical model of this system described as a self
      similar assembly of rigid pipes. It includes the specific geometry of the upper
      bronchial tree and a self-similar intermediary tree with a systematic branching
      asymmetry. It ends by the terminal bronchioles whose generations range from 8 to
      22. Unlike classical models, it does not rely on a simple scaling law. With a
      limited number of parameters, this model reproduces the morphometric data from
      various sources (Horsfield K, Dart G, Olson DE, Filley GF, Cumming G. J Appl
      Physiol 31: 207-217, 1971; Weibel ER. Morphometry of the Human Lung. New York:
      Academic Press, 1963) and the main characteristics of the ventilation. Studying
      various types of random variations of the airway sizes, we show that strong
      correlations are needed to reproduce the measured distributions. Moreover, the
      ventilation performances are observed to be robust against anatomical
      variability. The same methodology applied to the rat also permits building a
      geometrical model that reproduces the anatomical and ventilation characteristics
      of this animal. This simple model can be directly used as a common description of
      the entire tree in analytical or numerical studies such as the computation of air
      flow distribution or aerosol transport.

PMID- 21183628
TI  - Motor unit recruitment when neuromuscular electrical stimulation is applied over
      a nerve trunk compared with a muscle belly: triceps surae.
AB  - Neuromuscular electrical stimulation (NMES) can be delivered over a nerve trunk
      or muscle belly and can generate contractions by activating motor (peripheral
      pathway) and sensory (central pathway) axons. In the present experiments, we
      compared the peripheral and central contributions to plantar flexion contractions
      evoked by stimulation over the tibial nerve vs. the triceps surae muscles.
      Generating contractions through central pathways follows Henneman's size
      principle, whereby low-threshold motor units are activated first, and this may
      have advantages for rehabilitation. Statistical analyses were performed on data
      from trials in which NMES was delivered to evoke 10-30% maximum voluntary torque
      2-3 s into the stimulation (Time(1)). Two patterns of stimulation were delivered:
      1) 20 Hz for 8 s; and 2) 20-100-20 Hz for 3-2-3 s. Torque and soleus
      electromyography were quantified at the beginning (Time(1)) and end (Time(2); 6-7
      s into the stimulation) of each stimulation train. H reflexes (central pathway)
      and M waves (peripheral pathway) were quantified. Motor unit activity that was
      not time-locked to each stimulation pulse as an M wave or H reflex
      ("asynchronous" activity) was also quantified as a second measure of central
      recruitment. Torque was not different for stimulation over the nerve or the
      muscle. In contrast, M waves were approximately five to six times smaller, and H
      reflexes were approximately two to three times larger during NMES over the nerve
      vs. the muscle. Asynchronous activity increased by 50% over time, regardless of
      the stimulation location or pattern, and was largest during NMES over the muscle
      belly. Compared with NMES over the triceps surae muscles, NMES over the tibial
      nerve produced contractions with a relatively greater central contribution, and
      this may help reduce muscle atrophy and fatigue when NMES is used for
      rehabilitation.

PMID- 21183627
TI  - Genomic predictors of the maximal O2 uptake response to standardized exercise
      training programs.
AB  - Low cardiorespiratory fitness is a powerful predictor of morbidity and
      cardiovascular mortality. In 473 sedentary adults, all whites, from 99 families
      of the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family
      Study, the heritability of gains in maximal O(2) uptake (VO(2max)) after exposure
      to a standardized 20-wk exercise program was estimated at 47%. A genome-wide
      association study based on 324,611 single-nucleotide polymorphisms (SNPs) was
      undertaken to identify SNPs associated with improvements in VO(2max) Based on
      single-SNP analysis, 39 SNPs were associated with the gains with P < 1.5 * 10(
      4). Stepwise multiple regression analysis of the 39 SNPs identified a panel of 21
      SNPs that accounted for 49% of the variance in VO(2max) trainability. Subjects
      who carried <=9 favorable alleles at these 21 SNPs improved their VO(2max) by 221
      ml/min, whereas those who carried >=19 of these alleles gained, on average, 604
      ml/min. The strongest association was with rs6552828, located in the acyl-CoA
      synthase long-chain member 1 (ACSL1) gene, which accounted by itself for ~6% of
      the training response of VO(2max). The genes nearest to the SNPs that were the
      strongest predictors were PR domain-containing 1 with ZNF domain (PRDM1);
      glutamate receptor, ionotropic, N-methyl-D-aspartate 3A (GRIN3A); K(+) channel,
      voltage gated, subfamily H, member 8 (KCNH8); and zinc finger protein of the
      cerebellum 4 (ZIC4). The association with the SNP nearest to ZIC4 was replicated
      in 40- to 65-yr-old, sedentary, overweight, and dyslipidemic subjects trained in
      Studies of a Targeted Risk Reduction Intervention Through Defined Exercise
      (STRRIDE; n = 183). Two SNPs were replicated in sedentary obese white women
      exercise trained in the Dose Response to Exercise (DREW) study (n = 112):
      rs1956197 near dishevelled associated activator of morphogenesis 1 (DAAM1) and
      rs17117533 in the vicinity of necdin (NDN). The association of SNPs rs884736 in
      the calmodulin-binding transcription activator 1 (CAMTA1) locus and rs17581162
      ~68 kb upstream from regulator of G protein signaling 18 (RGS18) with the gains
      in VO(2max) in HERITAGE whites were replicated in HERITAGE blacks (n = 247).
      These genomic predictors of the response of Vo(2max) to regular exercise provide
      new targets for the study of the biology of fitness and its adaptation to regular
      exercise. Large-scale replication studies are warranted.

PMID- 21183629
TI  - Persistent disease and recurrence in differentiated thyroid cancer patients with
      undetectable postoperative stimulated thyroglobulin level.
AB  - (131)I is given in differentiated thyroid cancer (DTC) without taking into
      account thyroglobulin (Tg) levels at the time of ablation, whereas 6-18 months
      later it is a major criterion for cure. This single-center retrospective study
      assessed the frequency and risk factors for persistent disease on postablation
      whole body scan (WBS) and postoperative neck ultrasonography (n-US) and for
      recurrent disease during the subsequent follow-up, in patients with DTC and
      undetectable TSH-stimulated Tg level (TSH-Tg) in the absence of Tg antibodies
      (TgAb) at the time of ablation. Among 1031 patients ablated, 242 (23%)
      consecutive patients were included. Persistent disease occurred in eight cases
      (3%) (seven abnormal WBS and one abnormal n-US), all with initial neck lymph node
      metastases (N1). N1 was a major risk factor for persistent disease. Among 203
      patients with normal WBS and a follow-up over 6 months, TSH-Tg 6-18 months after
      ablation was undetectable in the absence of TgAb in 173 patients, undetectable
      with TgAb in 1 patient and equal to 1.2  ng/ml in 1 patient. n-US was normal in
      152 patients and falsely positive in 3 patients. After a mean follow-up of 4
      years, recurrence occurred in two cases (1%), both with aggressive histological
      variants. The only risk factor for recurrence was an aggressive histological
      variant (P = 0.03). In conclusion, undetectable postoperative TSH-Tg in the
      absence of TgAb at the time of ablation is frequent. In these patients, repeating
      TSH-Tg 6-18 months after ablation is not useful. (131)I ablation could be avoided
      in the absence of N1 and aggressive histological variant.

PMID- 21183630
TI  - Inactivation of murine norovirus 1, coliphage phiX174, and Bacteroides
      [corrected] fragilis phage B40-8 on surfaces and fresh-cut iceberg lettuce by
      hydrogen peroxide and UV light.
AB  - In this study, the inactivating properties of liquid hydrogen peroxide (L
      H(2)O(2)), vaporized hydrogen peroxide (V-H(2)O(2)), UV light, and a combination
      of V-H(2)O(2) and UV light were tested on murine norovirus 1 (MNV-1) and
      bacteriophages (phiX174 and B40-8) as models for human noroviruses. Disinfection
      of surfaces was examined on stainless steel discs based on European Standard EN
      13697 (2001). For fresh-produce decontamination, a mixture of the viruses was
      inoculated onto shredded iceberg lettuce and treated after overnight incubation
      at 2 degrees C. According to our results, L-H(2)O(2) (2.1%) was able to
      inactivate MNV-1 and phiX174 on stainless steel discs by approximately 4 log(10)
      units within 10 min of exposure, whereas for B40-8, 15% of L-H(2)O(2) was needed
      to obtain a similar reduction in 10 min. Only a marginal reduction (<=1 log(10)
      unit after 5 min of exposure) by V-H(2)O(2) (2.52%) was achieved for the tested
      model viruses, although in combination with UV light, a 4-log(10)-unit decrease
      within 5 min of treatment was observed on stainless steel discs. Similar trends
      were observed for the decontamination of shredded iceberg lettuce, but the viral
      decline was reduced. These results demonstrated that both L-H(2)O(2) and a
      combination of V-H(2)O(2) and UV light can be used for norovirus inactivation on
      surfaces; V-H(2)O(2) (2.52%) in combination with UV light is promising for
      decontamination of fresh produce with much less consumption of water and
      disinfectant.

PMID- 21183631
TI  - Novel structural elements within the nonproteolytic clostridium botulinum type F
      toxin gene cluster.
AB  - We sequenced for the first time the complete neurotoxin gene cluster of a
      nonproteolytic Clostridium botulinum type F. The neurotoxin gene cluster
      contained a novel gene arrangement that, compared to other C. botulinum
      neurotoxin gene clusters, lacked the regulatory botR gene and contained an
      intergenic is element between its orfX2 and orfX3 genes.

PMID- 21183632
TI  - Identification of candidate carrier proteins for surface display on Lactococcus
      lactis by theoretical and experimental analyses of the surface proteome.
AB  - Lactococcus lactis is a lactic acid bacterium of proven safety for use in human
      oral applications. For this purpose, surface display of recombinant proteins is
      important, and new approaches for it are being sought. Analysis of the bacterial
      surface proteome is essential in identifying new candidate carrier proteins for
      surface display. We have made two different predictions of surface-associated
      proteins of L. lactis MG1363 by using Augur and LocateP software, which yielded
      666 and 648 proteins, respectively. Surface proteins of L. lactis NZ9000, a
      derivative of MG1363, were identified by using a proteomics approach. The surface
      proteins were cleaved from intact bacteria, and the resulting peptides were
      identified by mass spectrometry. The latter approach yielded 80 proteins, 34 of
      which were not predicted by either software. Of the 80 proteins, 7 were selected
      for further study. These were cloned in frame with a C-terminal hexahistidine tag
      and overexpressed in L. lactis NZ9000 using nisin-controlled expression. Proteins
      of correct molecular weight carrying a hexahistidine tag were detected. Their
      surface localization was confirmed with flow cytometry. Basic membrane protein A
      (BmpA) was exposed at the highest level. To test BmpA as a candidate carrier
      protein, the hexahistidine tag was replaced by the B domain of staphylococcal
      protein A in the genetic construct. The B domain was displayed on the surface
      with BmpA as a carrier. The advantage of covalent BmpA binding was demonstrated.
      BmpA was thus shown to be a suitable candidate for a carrier protein in
      lactococcal surface display.

PMID- 21183633
TI  - Influence of two-component signal transduction systems of Lactobacillus casei
      BL23 on tolerance to stress conditions.
AB  - Lactobacillus casei BL23 carries 17 two-component signal transduction systems.
      Insertional mutations were introduced into each gene encoding the cognate
      response regulators, and their effects on growth under different conditions were
      assayed. Inactivation of systems TC01, TC06, and TC12 (LCABL_02080-LCABL_02090,
      LCABL_12050-LCABL_12060, and LCABL_19600-LCABL_19610, respectively) led to major
      growth defects under the conditions assayed.

PMID- 21183634
TI  - Metagenomic analysis of the viral communities in fermented foods.
AB  - Viruses are recognized as the most abundant biological components on Earth, and
      they regulate the structure of microbial communities in many environments. In
      soil and marine environments, microorganism-infecting phages are the most common
      type of virus. Although several types of bacteriophage have been isolated from
      fermented foods, little is known about the overall viral assemblages (viromes) of
      these environments. In this study, metagenomic analyses were performed on the
      uncultivated viral communities from three fermented foods, fermented shrimp,
      kimchi, and sauerkraut. Using a high-throughput pyrosequencing technique, a total
      of 81,831, 70,591 and 69,464 viral sequences were obtained from fermented shrimp,
      kimchi and sauerkraut, respectively. Moreover, 37 to 50% of these sequences
      showed no significant hit against sequences in public databases. There were some
      discrepancies between the prediction of bacteriophages hosts via homology
      comparison and bacterial distribution, as determined from 16S rRNA gene
      sequencing. These discrepancies likely reflect the fact that the viral genomes of
      fermented foods are poorly represented in public databases. Double-stranded DNA
      viral communities were amplified from fermented foods by using a linker-amplified
      shotgun library. These communities were dominated by bacteriophages belonging to
      the viral order Caudovirales (i.e., Myoviridae, Podoviridae, and Siphoviridae).
      This study indicates that fermented foods contain less complex viral communities
      than many other environmental habitats, such as seawater, human feces, marine
      sediment, and soil.

PMID- 21183635
TI  - Genome sequence and characterization of the Tsukamurella bacteriophage TPA2.
AB  - The formation of stable foam in activated sludge plants is a global problem for
      which control is difficult. These foams are often stabilized by hydrophobic
      mycolic acid-synthesizing Actinobacteria, among which are Tsukamurella spp. This
      paper describes the isolation from activated sludge of the novel double-stranded
      DNA phage TPA2. This polyvalent Siphoviridae family phage is lytic for most
      Tsukamurella species. Whole-genome sequencing reveals that the TPA2 genome is
      circularly permuted (61,440 bp) and that 70% of its sequence is novel. We have
      identified 78 putative open reading frames, 95 pairs of inverted repeats, and 6
      palindromes. The TPA2 genome has a modular gene structure that shares some
      similarity to those of Mycobacterium phages. A number of the genes display a
      mosaic architecture, suggesting that the TPA2 genome has evolved at least in part
      from genetic recombination events. The genome sequence reveals many novel genes
      that should inform any future discussion on Tsukamurella phage evolution.

PMID- 21183636
TI  - Involvement of an alkane hydroxylase system of Gordonia sp. strain SoCg in
      degradation of solid n-alkanes.
AB  - Enzymes involved in oxidation of long-chain n-alkanes are still not well known,
      especially those in gram-positive bacteria. This work describes the alkane
      degradation system of the n-alkane degrader actinobacterium Gordonia sp. strain
      SoCg, which is able to grow on n-alkanes from dodecane (C(12)) to hexatriacontane
      (C(36)) as the sole C source. SoCg harbors in its chromosome a single alk locus
      carrying six open reading frames (ORFs), which shows 78 to 79% identity with the
      alkane hydroxylase (AH)-encoding systems of other alkane-degrading
      actinobacteria. Quantitative reverse transcription-PCR showed that the genes
      encoding AlkB (alkane 1-monooxygenase), RubA3 (rubredoxin), RubA4 (rubredoxin),
      and RubB (rubredoxin reductase) were induced by both n-hexadecane and n
      triacontane, which were chosen as representative long-chain liquid and solid n
      alkane molecules, respectively. Biotransformation of n-hexadecane into the
      corresponding 1-hexadecanol was detected by solid-phase microextraction coupled
      with gas chromatography-mass spectrometry (SPME/GC-MS) analysis. The Gordonia
      SoCg alkB was heterologously expressed in Escherichia coli BL21 and in
      Streptomyces coelicolor M145, and both hosts acquired the ability to transform n
      hexadecane into 1-hexadecanol, but the corresponding long-chain alcohol was never
      detected on n-triacontane. However, the recombinant S. coelicolor M145-AH,
      expressing the Gordonia alkB gene, was able to grow on n-triacontane as the sole
      C source. A SoCg alkB disruption mutant that is completely unable to grow on n
      triacontane was obtained, demonstrating the role of an AlkB-type AH system in
      degradation of solid n-alkanes.

PMID- 21183637
TI  - Identification of the monooxygenase gene clusters responsible for the
      regioselective oxidation of phenol to hydroquinone in mycobacteria.
AB  - Mycobacterium goodii strain 12523 is an actinomycete that is able to oxidize
      phenol regioselectively at the para position to produce hydroquinone. In this
      study, we investigated the genes responsible for this unique regioselective
      oxidation. On the basis of the fact that the oxidation activity of M. goodii
      strain 12523 toward phenol is induced in the presence of acetone, we first
      identified acetone-induced proteins in this microorganism by two-dimensional
      electrophoretic analysis. The N-terminal amino acid sequence of one of these
      acetone-induced proteins shares 100% identity with that of the protein encoded by
      the open reading frame Msmeg_1971 in Mycobacterium smegmatis strain mc(2)155,
      whose genome sequence has been determined. Since Msmeg_1971, Msmeg_1972,
      Msmeg_1973, and Msmeg_1974 constitute a putative binuclear iron monooxygenase
      gene cluster, we cloned this gene cluster of M. smegmatis strain mc(2)155 and its
      homologous gene cluster found in M. goodii strain 12523. Sequence analysis of
      these binuclear iron monooxygenase gene clusters revealed the presence of four
      genes designated mimABCD, which encode an oxygenase large subunit, a reductase,
      an oxygenase small subunit, and a coupling protein, respectively. When the mimA
      gene (Msmeg_1971) of M. smegmatis strain mc(2)155, which was also found to be
      able to oxidize phenol to hydroquinone, was deleted, this mutant lost the
      oxidation ability. This ability was restored by introduction of the mimA gene of
      M. smegmatis strain mc(2)155 or of M. goodii strain 12523 into this mutant.
      Interestingly, we found that these gene clusters also play essential roles in
      propane and acetone metabolism in these mycobacteria.

PMID- 21183638
TI  - Development and application of a tool to assess laboratory hygiene in contained
      use facilities.
AB  - To gain information on laboratory hygiene in contained-use laboratories, a method
      was developed to study the presence of microorganisms on laboratory equipment.
      Focusing detection on genetically modified organisms (GMOs) containing the
      universal M13 primer binding sites enabled the detection of a broad range of GMOs
      using a single PCR. Swabbing surfaces in three different contained-use
      laboratories led to detection of M13-containing PCR products in 26 out of 34
      swabs. Most sequences (up to five per sample) were detected in swabs from the
      centrifuge and sink, followed by swabs taken from the bin and incubator (up to
      four sequences per sample). The obtained sequences varied in length from 171
      nucleotides (nt) to 878 nt. In most cases, sequences were only partially similar
      to sequences published in GenBank. The lengths of the regions with high
      similarity varied from 94 nt to 795 nt, and these similarities ranged from 81% to
      100%. Similarities with more than one sequence were commonly found, complicating
      the identification of detected sequences. Nonetheless, 84% of the detected
      sequences were actually handled in the laboratory at the time of sampling. This
      demonstrates that the method may be used as a quality control tool to assess the
      efficacy of decontamination and cleaning of commonly used surfaces, such as
      laboratory benches, freezer doors, and centrifuge rotors, without prior knowledge
      of the identity or characteristics of the GMOs.

PMID- 21183639
TI  - Novel antibacterial proteins from the microbial communities associated with the
      sponge Cymbastela concentrica and the green alga Ulva australis.
AB  - The functional metagenomic screening of the microbial communities associated with
      a temperate marine sponge and a green alga identified three novel hydrolytic
      enzymes with antibacterial activities. The results suggest that uncultured alpha-
      and gammaproteobacteria contain new classes of proteins that may be a source of
      antibacterial agents.

PMID- 21183640
TI  - Bacterial endosymbiont localization in Hyalesthes obsoletus, the insect vector of
      Bois noir in Vitis vinifera.
AB  - One emerging disease of grapevine in Europe is Bois noir (BN), a phytoplasmosis
      caused by "Candidatus Phytoplasma solani" and spread in vineyards by the
      planthopper Hyalesthes obsoletus (Hemiptera: Cixiidae). Here we present the first
      full characterization of the bacterial community of this important disease vector
      collected from BN-contaminated areas in Piedmont, Italy. Length heterogeneity PCR
      and denaturing gradient gel electrophoresis analysis targeting the 16S rRNA gene
      revealed the presence of a number of bacteria stably associated with the insect
      vector. In particular, symbiotic bacteria detected by PCR with high infection
      rates in adult individuals fell within the "Candidatus Sulcia muelleri" cluster
      in the Bacteroidetes and in the "Candidatus Purcelliella pentastirinorum" group
      in the Gammaproteobacteria, both previously identified in different leafhoppers
      and planthoppers. A high infection rate (81%) was also shown for another symbiont
      belonging to the Betaproteobacteria, designated the HO1-V symbiont. Because of
      the low level of 16S rRNA gene identity (80%) with the closest relative, an
      uncharacterized symbiont of the tick Haemaphysalis longicornis, we propose the
      new name "Candidatus Vidania fulgoroideae." Other bacterial endosymbionts
      identified in H. obsoletus were related to the intracellular bacteria Wolbachia
      pipientis, Rickettsia sp., and "Candidatus Cardinium hertigii." Fluorescent in
      situ hybridization coupled with confocal laser scanning microscopy and
      transmission electron microscopy showed that these bacteria are localized in the
      gut, testicles, and oocytes. As "Ca. Sulcia" is usually reported in association
      with other symbiotic bacteria, we propose that in H. obsoletus, it may occur in a
      bipartite or even tripartite relationship between "Ca. Sulcia" and "Ca.
      Purcelliella," "Ca. Vidania," or both.

PMID- 21183641
TI  - Longitudinal evaluation of the efficacy of heat treatment procedures against
      Legionella spp. in hospital water systems by using a flow cytometric assay.
AB  - Legionella spp. are frequently isolated in hospital water systems. Heat shock (30
      min at 70 degrees C) is recommended by the World Health Organization to control
      its multiplication. The aim of the study was to evaluate retrospectively the
      efficacy of heat treatments by using a flow cytometry assay (FCA) able to
      identify viable but nonculturable (VBNC) cells. The study included Legionella
      strains (L. pneumophila [3 clusters] and L. anisa [1 cluster]) isolated from four
      hot water circuits of different hospital buildings in Saint-Etienne, France,
      during a 20-year prospective surveillance. The strains recovered from the
      different circuits were not epidemiologically related, but the strains isolated
      within a same circuit over time exhibited an identical genotypic profile. After
      an in vitro treatment of 30 min at 70 degrees C, the mean percentage of viable
      cells and VBNC cells varied from 4.6% to 71.7%. The in vitro differences in heat
      sensitivity were in agreement with the observed efficacy of preventive and
      corrective heating measures used to control water contamination. These results
      suggest that Legionella strains can become heat resistant after heating
      treatments for a long time and that flow cytometry could be helpful to check the
      efficacy of heat treatments on Legionella spp. and to optimize the
      decontamination processes applied to water systems for the control of Legionella
      proliferation.

PMID- 21183642
TI  - Nationwide groundwater surveillance of noroviruses in South Korea, 2008.
AB  - To inspect the norovirus contamination of groundwater in South Korea, a
      nationwide study was performed in the summer (June to August) and winter (October
      to December) of 2008. Three-hundred sites designated by the government ministry
      were inspected. Water samples were collected for analysis of water quality,
      microorganism content, and viral content. Water quality was assessed by
      temperature, pH, turbidity, residual chlorine, and nitrite nitrogen content.
      Microorganism contents were analyzed bacteria, total coliforms, Escherichia coli,
      and bacteriophage. Virus analyses included panenterovirus and norovirus. Two
      primer sets were used for the detection of norovirus genotypes GI and GII,
      respectively. Of 300 samples, 65 (21.7%) were norovirus positive in the summer
      and in 52 (17.3%) were norovirus positive in the winter. The genogroup GI
      noroviruses that were identified were GI-1, GI-2, GI-3, GI-4, GI-5, GI-6, and GI
      8 genotypes; those in the GII genogroup were GII-4 and GII-Yuri genotypes. The
      analytic data showed correlative relationships between the norovirus detection
      rate and the following parameters: water temperature and turbidity in physical
      chemical parameters and somatic phage in microbial parameters. It is necessary to
      periodically monitor waterborne viruses that frequently cause epidemic food
      poisoning in South Korea for better public health and sanitary conditions.

PMID- 21183643
TI  - Cytoplasmic and periplasmic proteomic signatures of exponentially growing cells
      of the psychrophilic bacterium Pseudoalteromonas haloplanktis TAC125.
AB  - The psychrophilic model bacterium Pseudoalteromonas haloplanktis is characterized
      by remarkably fast growth rates under low-temperature conditions in a range from
      5 degrees C to 20 degrees C. In this study the proteome of cellular compartments,
      the cytoplasm and periplasm, of P. haloplanktis strain TAC125 was analyzed under
      exponential growth conditions at a permissive temperature of 16 degrees C. By
      means of two-dimensional protein gel electrophoresis and mass spectrometry, a
      first inventory of the most abundant cytoplasmic and periplasmic proteins
      expressed in a peptone-supplemented minimal medium was established. By this
      approach major enzymes of the amino acid catabolism of this marine bacterium
      could be functionally deduced. The cytoplasmic proteome showed a predominance of
      amino acid degradation pathways and tricarboxylic acid (TCA) cycle enzymes but
      also the protein synthesis machinery. Furthermore, high levels of cold
      acclimation and oxidative stress proteins could be detected at this moderate
      growth temperature. The periplasmic proteome was characterized by a significant
      abundance of transporters, especially of highly expressed putative TonB-dependent
      receptors. This high capacity for protein synthesis, efficient amino acid
      utilization, and substrate transport may contribute to the fast growth rates of
      the copiotrophic bacterium P. haloplanktis in its natural environments.

PMID- 21183644
TI  - Development and application of a method for counterselectable in-frame deletion
      in Clostridium perfringens.
AB  - Many pathogenic clostridial species produce toxins and enzymes. To facilitate
      genome-wide identification of virulence factors and biotechnological application
      of their useful products, we have developed a markerless in-frame deletion method
      for Clostridium perfringens which allows efficient counterselection and multiple
      gene disruption. The system comprises a galKT gene disruptant and a suicide galK
      plasmid into which two fragments of a target gene for in-frame deletion are
      cloned. The system was shown to be accurate and simple by using it to disrupt the
      alpha-toxin gene of the organism. It was also used to construct of two different
      virulence-attenuated strains, EtaNu1303 and HN1314: the former is a disruptant of
      the virRS operon, which regulates the expression of virulence factors, and the
      latter is a disruptant of the six genes encoding the alpha, theta, and kappa
      toxins; a clostripain-like protease; a 190-kDa secretory protein; and a putative
      cell wall lytic endopeptidase. Comparison of the two disruptants in terms of
      growth ability and the background levels of secreted proteins showed that HN1314
      is more useful than EtaNu1303 as a host for the large-scale production of
      recombinant proteins.

PMID- 21183645
TI  - New insights into the genetic organization of the FK228 biosynthetic gene cluster
      in Chromobacterium violaceum no. 968.
AB  - The biosynthetic gene cluster of FK228, an FDA-approved anticancer natural
      product, was identified and sequenced previously. The genetic organization of
      this gene cluster has now been delineated through systematic gene deletion and
      transcriptional analysis. As a result, the gene cluster is redefined to contain
      12 genes: depA through depJ, depM, and a newly identified pathway regulatory
      gene, depR.

PMID- 21183646
TI  - Accessing the soil metagenome for studies of microbial diversity.
AB  - Soil microbial communities contain the highest level of prokaryotic diversity of
      any environment, and metagenomic approaches involving the extraction of DNA from
      soil can improve our access to these communities. Most analyses of soil
      biodiversity and function assume that the DNA extracted represents the microbial
      community in the soil, but subsequent interpretations are limited by the DNA
      recovered from the soil. Unfortunately, extraction methods do not provide a
      uniform and unbiased subsample of metagenomic DNA, and as a consequence, accurate
      species distributions cannot be determined. Moreover, any bias will propagate
      errors in estimations of overall microbial diversity and may exclude some
      microbial classes from study and exploitation. To improve metagenomic approaches,
      investigate DNA extraction biases, and provide tools for assessing the relative
      abundances of different groups, we explored the biodiversity of the accessible
      community DNA by fractioning the metagenomic DNA as a function of (i) vertical
      soil sampling, (ii) density gradients (cell separation), (iii) cell lysis
      stringency, and (iv) DNA fragment size distribution. Each fraction had a unique
      genetic diversity, with different predominant and rare species (based on
      ribosomal intergenic spacer analysis [RISA] fingerprinting and phylochips). All
      fractions contributed to the number of bacterial groups uncovered in the
      metagenome, thus increasing the DNA pool for further applications. Indeed, we
      were able to access a more genetically diverse proportion of the metagenome (a
      gain of more than 80% compared to the best single extraction method), limit the
      predominance of a few genomes, and increase the species richness per sequencing
      effort. This work stresses the difference between extracted DNA pools and the
      currently inaccessible complete soil metagenome.

PMID- 21183647
TI  - Essential role of YlMPO1, a novel Yarrowia lipolytica homologue of Saccharomyces
      cerevisiae MNN4, in mannosylphosphorylation of N- and O-linked glycans.
AB  - Mannosylphosphorylation of N- and O-glycans, which confers negative charges on
      the surfaces of cells, requires the functions of both MNN4 and MNN6 in
      Saccharomyces cerevisiae. To identify genes relevant to mannosylphosphorylation
      in the dimorphic yeast Yarrowia lipolytica, the molecular functions of five Y.
      lipolytica genes showing significant sequence homology with S. cerevisiae MNN4
      and MNN6 were investigated. A set of mutant strains in which Y. lipolytica MNN4
      and MNN6 homologues were deleted underwent glycan structure analysis. In contrast
      to S. cerevisiae MNN4 (ScMNN4), the Y. lipolytica MNN4 homologue, MPO1 (YlMPO1),
      encodes a protein that lacks the long KKKKEEEE repeat domain at its C terminus.
      Moreover, just a single disruption of YlMPO1 resulted in complete disappearance
      of the acidic sugar moiety in both the N- and O-linked glycan profiles. In
      contrast, even quadruple disruption of all ScMNN6 homologues, designated YlKTR1,
      YlKTR2, YlKTR3, and YlKTR4, resulted in no apparent reduction in acidic sugar
      moieties. These findings strongly indicate that YlMpo1p performs a significant
      role in mannosylphosphorylation in Y. lipolytica with no involvement of the Mnn6p
      homologues. Mutant strains harboring the YlMPO1 gene disruption may serve as
      useful platforms for engineering Y. lipolytica glycosylation pathways for
      humanized glycans without any yeast-specific acidic modifications.

PMID- 21183648
TI  - Reconstitution of the FK228 biosynthetic pathway reveals cross talk between
      modular polyketide synthases and fatty acid synthase.
AB  - Functional cross talk between fatty acid biosynthesis and secondary metabolism
      has been discovered in several cases in microorganisms; none of them, however,
      involves a modular biosynthetic enzyme. Previously, we reported a hybrid modular
      nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) pathway for the
      biosynthesis of FK228 anticancer depsipeptide in Chromobacterium violaceum strain
      968. This pathway contains two PKS modules on the DepBC enzymes that lack a
      functional acyltransferase (AT) domain, and no apparent AT-encoding gene exists
      within the gene cluster or its vicinity. We report here that, through
      reconstitution of the FK228 biosynthetic pathway in Escherichia coli cells, two
      essential genes, fabD1 and fabD2, both encoding a putative malonyl coenzyme A
      (CoA) acyltransferase component of the fatty acid synthase complex, are
      positively identified to be involved in FK228 biosynthesis. Either gene product
      appears sufficient to complement the AT-less PKS modules on DepBC for polyketide
      chain elongation. Concurrently, a gene (sfp) encoding a putative Sfp-type
      phosphopantetheinyltransferase was identified to be necessary for FK228
      biosynthesis as well. Most interestingly, engineered E. coli strains carrying
      variable genetic components produced significant levels of FK228 under both
      aerobic and anaerobic cultivation conditions. Discovery of the trans
      complementation of modular PKSs by housekeeping ATs reveals natural product
      biosynthesis diversity. Moreover, demonstration of anaerobic production of FK228
      by an engineered facultative bacterial strain validates our effort toward the
      engineering of novel tumor-targeting bioagents.

PMID- 21183649
TI  - Characterization of a phosphotriesterase-like lactonase from Sulfolobus
      solfataricus and its immobilization for disruption of quorum sensing.
AB  - SsoPox, a bifunctional enzyme with organophosphate hydrolase and N-acyl
      homoserine lactonase activities from the hyperthermophilic archaeon Sulfolobus
      solfataricus, was overexpressed and purified from recombinant Pseudomonas putida
      KT2440 with a yield of 9.4 mg of protein per liter of culture. The enzyme has a
      preference for N-acyl homoserine lactones (AHLs) with acyl chain lengths of at
      least 8 carbon atoms, mainly due to lower K(m) values for these substrates. The
      highest specificity constant obtained was for N-3-oxo-decanoyl homoserine lactone
      (k(cat)/K(m) = 5.5 * 10(3) M(-1).s(-1)), but SsoPox can also degrade N-butyryl
      homoserine lactone (C(4)-HSL) and N-oxo-dodecanoyl homoserine lactone (oxo-C(12)
      HSL), which are important for quorum sensing in our Pseudomonas aeruginosa model
      system. When P. aeruginosa PAO1 cultures were grown in the presence of SsoPox
      immobilized membranes, the production of C(4)-HSL- and oxo-C(12)-HSL-regulated
      virulence factors, elastase, protease, and pyocyanin were significantly reduced.
      This is the first demonstration that immobilized quorum-quenching enzymes can be
      used to attenuate the production of virulence factors controlled by quorum
      sensing signals.

PMID- 21183650
TI  - Identification of enterococci from broiler products and a broiler processing
      plant and description of Enterococcus viikkiensis sp. nov.
AB  - In two previous studies dealing with lactic acid bacteria (LAB) from modified
      atmosphere-packaged (MAP) broiler products and a broiler processing plant,
      several isolates remained unidentified. According to 16S rRNA gene sequence
      analysis, 36 isolates were assigned to the genus Enterococcus. Numerical analysis
      of combined HindIII and EcoRI ribopatterns of these isolates resulted in species
      specific clusters that were congruent with the clusters obtained by both DNA
      directed RNA polymerase subunit A (rpoA) and phenylalanyl-tRNA synthetase alpha
      chain (pheS) housekeeping gene analyses. In the analyses, a group of five
      isolates distinct from any known enterococcal species clustered together. The
      five isolates were positioned in the Enterococcus avium group, with E. devriesei
      being the closest phylogenetic neighbor. The DNA-DNA hybridization levels with E.
      devriesei ranged from 28.8 to 54.3% and indicated that these strains represented
      a novel species. The name Enterococcus viikkiensis sp. nov. is proposed, with
      strain DSM 24043(T) (LMG 26075(T)) being the type strain. Our study demonstrated
      that the identification of enterococci within the E. avium phylogenetic group
      demands polyphasic taxonomic approaches. The rpoA and pheS gene similarities
      (99.0 to 99.2% and 94.3 to 95.4%, respectively) between E. viikkiensis and its
      closest phylogenetic neighbor, E. devriesei, were higher than those previously
      reported within the enterococci. In addition, the phenotypic profiles of the
      species in the E. avium group were also highly similar, and some traits were
      found to be misleading for enterococci, such as E. viikkiensis does not grow at
      45 degrees C. The numerical analysis of combined HindIII and EcoRI ribopatterns
      was of considerable assistance in distinguishing enterococcal species within the
      E. avium group.

PMID- 21183651
TI  - Sex differences in the prevalence of peripheral artery disease in patients
      undergoing coronary catheterization.
AB  - To determine whether there are sex differences in the prevalence of peripheral
      artery disease, we performed an observational study of 1014 men and 547 women,
      aged >= 40 years, referred for elective coronary angiography. Women were slightly
      older, more obese, had higher low-density lipoprotein cholesterol (LDL-C) levels
      and systolic blood pressure (BP), and were more likely to be African American.
      Women had higher high-density lipoprotein cholesterol (HDL-C) levels, lower
      diastolic BP, and were less likely to smoke or to have a history of
      cardiovascular disease. Women had less prevalent (62% vs 81%) and less severe
      coronary artery disease (CAD) (p < 0.001 for both) by coronary angiography, but
      more prevalent peripheral artery disease (PAD) as determined by the ankle
      brachial index (ABI) than men (23.6% versus 17.2%). Independent predictors of
      lower ABI were female sex, black race, older age, tobacco use, CAD, diabetes, and
      triglyceride level. In a full multivariable logistic regression model, women had
      a risk-adjusted odds ratio for PAD of 1.78 (95% CI 1.25-2.54) relative to men.
      Among patients referred for coronary angiography, women have less prevalent and
      less severe CAD, but more prevalent PAD, a sex difference that is not explained
      by traditional cardiovascular disease risk factors or CAD severity. Clinical
      Trial Registration-URL: http://clinicaltrials.gov. Unique identifier:
      NCT00380185.

PMID- 21183652
TI  - Inferior vena cava agenesis and deep vein thrombosis: 10 patients and review of
      the literature.
AB  - Inferior vena cava agenesis (IVCA) is a rare condition, found in almost 5% of
      patients under 30 years old with unprovoked deep venous thrombosis (DVT). We
      describe 10 consecutive patients with IVCA-associated DVT and conducted an
      extensive literature review to investigate the typical spectrum of IVCA
      associated DVT. Among our patients (eight men and two women; mean age, 25 +/- 4.5
      years), DVT followed intense and unusual (major) physical activity for eight of
      them. DVT was bilateral in six patients and unilateral in four. Ultrasonography
      was unable to detect IVCA, which was visualized by computed-tomography scans for
      seven patients, and magnetic resonance imaging and angiography for 10. Hereditary
      thrombophilia screening, to detect factor V Leiden or prothrombin gene
      heterozygosity (G20210A mutation), was positive for only two patients. Wearing
      elastic stockings and taking an indefinite or long-term vitamin K antagonist were
      prescribed for all 10 patients and nine complied with the latter. To date, 62
      patients with IVCA-associated DVT have been reported in the English literature.
      Analysis of them and our patients yielded a typical spectrum of IVCA-associated
      DVT characteristics: IVCA occurs in young adults, particularly males, and is
      revealed by proximal DVT following major physical exertion. All were treated with
      a prolonged vitamin K antagonist and advised to wear elastic stockings. No
      precise duration of anticoagulation has been established.

PMID- 21183656
TI  - Many routes to the same destination: lessons from skeletal muscle development.
AB  - The development and differentiation of vertebrate skeletal muscle provide an
      important paradigm to understand the inductive signals and molecular events
      controlling differentiation of specific cell types. Recent findings show that a
      core transcriptional network, initiated by the myogenic regulatory factors (MRFs;
      MYF5, MYOD, myogenin and MRF4), is activated by separate populations of cells in
      embryos in response to various signalling pathways. This review will highlight
      how cells from multiple distinct starting points can converge on a common set of
      regulators to generate skeletal muscle.

PMID- 21183653
TI  - ACCF/AHA/ACR/SCAI/SIR/SVM/SVN/SVS 2010 performance measures for adults with
      peripheral artery disease. A Report of the American College of Cardiology
      Foundation/American Heart Association Task Force on Performance Measures, the
      American College of Radiology, the Society for Cardiac Angiography and
      Interventions, the Society for Interventional Radiology, the Society for Vascular
      Medicine, the Society for Vascular Nursing, and the Society for Vascular Surgery
      (Writing Committee to Develop Clinical Performance Measures for Peripheral Artery
      Disease).

PMID- 21183657
TI  - Pcsk6 mutant mice exhibit progressive loss of ovarian function, altered gene
      expression, and formation of ovarian pathology.
AB  - Bioactivation of precursor proteins by members of the proprotein convertase (PC)
      family is essential for normal reproduction. The Pcsk6 gene is a member of the PC
      family that is expressed in numerous ovarian cell types including granulosa cells
      and oocytes. We hypothesized that loss of PCSK6 would produce adverse effects in
      the mouse ovary. Mice incapable of expressing PCSK6 (Pcsk6(tm1Rob)) were
      obtained, and reproductive parameters (serum hormones, whelping interval, estrus
      cyclicity, and fertility) were compared to Pcsk6(+/+) mice. While Pcsk6(tm1Rob)
      female mice are fertile, they manifest reduced reproductive capacity at an
      accelerated rate relative to Pcsk6(+/+) mice. Reproductive senescence is
      typically reached by 9 months of age and is correlated with loss of estrus
      cyclicity, elevated serum FSH levels, and gross alterations in ovarian
      morphology. A wide range of ovarian morphologies were identified encompassing
      mild, such as an apparent reduction in follicle number, to moderate--ovarian
      atrophy with a complete absence of follicles--to severe, manifesting as normal
      ovarian structures replaced by benign ovarian tumors, including tubulostromal
      adenomas. Targeted gene expression profiling highlighted changes in RNA
      expression of molecules involved in processes such as steroidogenesis,
      gonadotropin signaling, transcriptional regulation, autocrine/paracrine
      signaling, cholesterol handling, and proprotein bioactivation. These results show
      that PCSK6 activity plays a role in maintaining normal cellular and tissue
      homeostasis in the ovary.

PMID- 21183658
TI  - Sorting mouse jejunal epithelial cells with CD24 yields a population with
      characteristics of intestinal stem cells.
AB  - Intestinal stem cells (ISCs) have been studied for more than three decades;
      however, their isolation has remained a challenge. We hypothesized that, just as
      for stem cells of other tissues, one or more membrane markers would allow
      positive selection of ISCs by antibody-based sorting. To explore this hypothesis,
      microarray data of putative ISC fractions generated by side population sorting
      and laser capture microdissection were subjected to bioinformatic analysis to
      identify common membrane antigens. The microarray comparison suggested CD24 as a
      candidate surface marker, and immunohistochemistry showed expression of CD24 in
      epithelial cells of crypt bases. Flow cytometry of jejunal epithelial
      preparations revealed a CD24(+) CD45(-) fraction comprising ~1% of the cells.
      Analysis with epithelial cell adhesion molecule and CD31 confirmed that the cell
      preparations were epithelial and without endothelial contamination. Cycling cells
      identified by prior injection with 5-ethynyl-2'-deoxyuridine were found
      predominantly in the CD24(lo) subfraction. Transcript analysis by real-time RT
      PCR showed this subfraction to be enriched in the ISC markers leucine-rich-repeat
      containing G-protein-coupled receptor 5 (40-fold) and Bmi1 (5-fold), but also
      enriched in lysozyme (10-fold). Flow cytometry with anti-lysozyme antibodies
      demonstrated that Paneth cells comprise ~30% of the CD24(lo) subfraction.
      Additional flow analyses with leucine-rich-repeat-containing G-protein-coupled
      receptor 5-enhanced green fluorescent protein (EGFP) epithelium demonstrated
      colocalization of EGFP(hi) and CD24(lo). In contrast, CD24 cells were negative
      for the quiescent ISC marker doublecortin and CaM kinase-like-1. Culture of
      CD24(lo) cells in Matrigel generated organoid structures, which included all four
      epithelial lineages, thus giving functional evidence for the presence of ISCs. We
      conclude that the CD24(lo) fraction of jejunal epithelium is highly enriched with
      cycling ISCs. This isolation method should be useful to many investigators in the
      field to advance both the basic understanding of ISC biology and the therapeutic
      applications of ISCs.

PMID- 21183659
TI  - Association of PDZ-containing protein PDZD11 with the human sodium-dependent
      multivitamin transporter.
AB  - Intestinal absorption of biotin is mediated via the sodium-dependent multivitamin
      transporter (SMVT). Studies from our laboratory and others have characterized
      different aspects of the human SMVT (hSMVT), but nothing is currently known about
      protein(s) that may interact with hSMVT and affect its physiology/biology. In
      this study, a PDZ-containing protein PDZD11 was identified as an interacting
      partner with hSMVT using yeast two-hybrid screen of a human intestinal cDNA
      library. The interaction between hSMVT and PDZD11 was confirmed by in vitro GST
      pull-down assay and in vivo in a mammalian cell environment by a two-hybrid
      luciferase and coimmunoprecipitation assays. Furthermore, confocal imaging of
      live human intestinal epithelial HuTu-80 cells expressing hSMVT-GFP and DsRed
      PDZD11 demonstrated colocalization of these two proteins. We also examined the
      functional consequence of the interaction between hSMVT and PDZD11 in HuTu-80
      cells and observed significant induction in [(3)H]biotin uptake upon coexpression
      of hSMVT and PDZD11. In contrast, knocking down of PDZD11 with gene-specific
      small interfering RNA led to a significant decrease in biotin uptake;
      biotinylation assay showed this to be associated with a marked decrease in level
      of expression of hSMVT at the cell membrane. By truncation approach, we also
      demonstrated that the PDZ binding domain that is located in the COOH-terminal
      tail of hSMVT polypeptide is involved in the interaction with PDZD11. These
      results demonstrate for the first time that PDZD11 is an interacting partner with
      hSMVT in intestinal epithelial cells and that this interaction affects hSMVT
      function and cell biology.

PMID- 21183660
TI  - Hypoxia-inducible factor plays a gut-injurious role in intestinal ischemia
      reperfusion injury.
AB  - Gut injury and loss of normal intestinal barrier function are key elements in the
      paradigm of gut-origin systemic inflammatory response syndrome, acute lung
      injury, and multiple organ dysfunction syndrome (MODS). As hypoxia-inducible
      factor (HIF-1) is a critical determinant of the physiological and
      pathophysiological response to hypoxia and ischemia, we asked whether HIF-1 plays
      a proximal role in the induction of gut injury and subsequent lung injury. Using
      partially HIF-1alpha-deficient mice in an isolated superior mesenteric artery
      occlusion (SMAO) intestinal ischemia reperfusion (I/R) injury model (45 min SMAO
      followed by 3 h of reperfusion), we showed a direct relationship between HIF-1
      activation and intestinal I/R injury. Specifically, partial HIF-1alpha deficiency
      attenuated SMAO-induced increases in intestinal permeability, lipid peroxidation,
      mucosal caspase-3 activity, and IL-1beta mRNA levels. Furthermore, partial HIF
      1alpha deficiency prevented the induction of ileal mucosal inducible nitric oxide
      synthase (iNOS) protein levels after SMAO and iNOS deficiency ameliorated SMAO
      induced villus injury. Resistance to SMAO-induced gut injury was also associated
      with resistance to lung injury, as reflected by decreased levels of
      myeloperoxidase, IL-6 and IL-10 in the lungs of HIF-1alpha(+/-) mice. In
      contrast, a short duration of SMAO (15 min) followed by 3 h of reperfusion
      neither induced mucosal HIF-1alpha protein levels nor caused significant gut and
      lung injury in wild-type or HIF-1alpha(+/-) mice. This study indicates that
      intestinal HIF-1 activation is a proximal regulator of I/R-induced gut mucosal
      injury and gut-induced lung injury. However, the duration and severity of the gut
      I/R insult dictate whether HIF-1 plays a gut-protective or deleterious role.

PMID- 21183661
TI  - PDZK1 binding and serine phosphorylation regulate subcellular trafficking of
      organic anion transport protein 1a1.
AB  - Although perturbation of organic anion transport protein (oatp) cell surface
      expression can result in drug toxicity, little is known regarding mechanisms
      regulating its subcellular distribution. Many members of the oatp family,
      including oatp1a1, have a COOH-terminal PDZ consensus binding motif that
      interacts with PDZK1, while serines upstream of this site (S634 and S635) can be
      phosphorylated. Using oatp1a1 as a prototypical member of the oatp family, we
      prepared plasmids in which these serines were mutated to glutamic acid [E634E635
      (oatp1a1(EE)), phosphomimetic] or alanine [A634A635 (oatp1a1(AA)),
      nonphosphorylatable]. Distribution of oatp1a1(AA) and oatp1a1(EE) was largely
      intracellular in transfected human embryonic kidney (HEK) 293T cells.
      Cotransfection with a plasmid encoding PDZK1 revealed that oatp1a1(AA) was now
      expressed largely on the cell surface, while oatp1a1(EE) remained intracellular.
      To quantify these changes, studies were performed in HuH7 cells stably
      transfected with these oatp1a1 plasmids. These cells endogenously express PDZK1.
      Surface biotinylation at 4 degrees C followed by shift to 37 degrees C showed
      that oatp1a1(EE) internalizes quickly compared with oatp1a1(AA). To examine a
      physiological role for phosphorylation in oatp1a1 subcellular distribution,
      studies were performed in rat hepatocytes exposed to extracellular ATP, a
      condition that stimulates serine phosphorylation of oatp1a1 via activity of a
      purinergic receptor. Internalization of oatp1a1 under these conditions was rapid.
      Thus, although PDZK1 binding is required for optimal cell surface expression of
      oatp1a1, phosphorylation provides a mechanism for fast regulation of the
      distribution of oatp1a1 between the cell surface and intracellular vesicular
      pools. Identification of the proteins and motor molecules that mediate these
      trafficking events represents an important area for future study.

PMID- 21183663
TI  - Genome sequence of Bacillus subtilis subsp. spizizenii gtP20b, isolated from the
      Indian ocean.
AB  - Bacillus subtilis is an aerobic spore-forming Gram-positive bacterium that is a
      model organism and of great industrial significance as the source of diverse
      novel functional molecules. Here we present, to our knowledge, the first genome
      sequence of Bacillus subtilis strain gtP20b isolated from the marine environment.
      A subset of candidate genes and gene clusters were identified, which are
      potentially involved in production of diverse functional molecules, like novel
      ribosomal and nonribosomal antimicrobial peptides. The genome sequence described
      in this paper is due to its high strain specificity of great importance for basic
      as well as applied researches on marine organisms.

PMID- 21183662
TI  - Amino acids stimulate cholecystokinin release through the Ca2+-sensing receptor.
AB  - Cholecystokinin (CCK) is produced by discrete endocrine cells in the proximal
      small intestine and is released following the ingestion of food. CCK is the
      primary hormone responsible for gallbladder contraction and has potent effects on
      pancreatic secretion, gastric emptying, and satiety. In addition to fats,
      digested proteins and aromatic amino acids are major stimulants of CCK release.
      However, the cellular mechanism by which amino acids affect CCK secretion is
      unknown. The Ca(2+)-sensing receptor (CaSR) that was originally identified on
      parathyroid cells is not only sensitive to extracellular Ca(2+) but is activated
      by extracellular aromatic amino acids. It has been postulated that this receptor
      may be involved in gastrointestinal hormone secretion. Using transgenic mice
      expressing a CCK promoter driven/enhanced green fluorescent protein (GFP)
      transgene, we have been able to identify and purify viable intestinal CCK cells.
      Intestinal mucosal CCK cells were enriched >200-fold by fluorescence-activated
      cell sorting. These cells were then used for real-time PCR identification of
      CaSR. Immunohistochemical staining with an antibody specific for CaSR confirmed
      colocalization of CaSR to CCK cells. In isolated CCK cells loaded with a Ca(2+)
      sensitive dye, the amino acids phenylalanine and tryptophan, but not nonaromatic
      amino acids, caused an increase in intracellular Ca(2+) ([Ca(2+)](i)). The
      increase in [Ca(2+)](i) was blocked by the CaSR inhibitor Calhex 231.
      Phenylalanine and tryptophan stimulated CCK release from intestinal CCK cells,
      and this stimulation was also blocked by CaSR inhibition. Electrophysiological
      recordings from isolated CCK-GFP cells revealed these cells to possess a
      predominant outwardly rectifying potassium current. Administration of
      phenylalanine inhibited basal K(+) channel activity and caused CCK cell
      depolarization, consistent with changes necessary for hormone secretion. These
      findings indicate that amino acids have a direct effect on CCK cells to stimulate
      CCK release by activating CaSR and suggest that CaSR is the physiological
      mechanism through which amino acids regulate CCK secretion.

PMID- 21183665
TI  - Genome sequence of Lactobacillus animalis KCTC 3501.
AB  - Lactobacillus animalis is one of the most prevalent lactic acid bacteria present
      during the manufacturing process of kimchi, the best-known traditional Korean
      dish. Here, we present the draft genome sequence of Lactobacillus animalis type
      strain KCTC 3501 (1,882,795 bp, with a G+C content of 41.1%), which consists of 7
      scaffolds.

PMID- 21183664
TI  - Complete genome sequence of the metabolically versatile plant growth-promoting
      endophyte Variovorax paradoxus S110.
AB  - Variovorax paradoxus is a microorganism of special interest due to its diverse
      metabolic capabilities, including the biodegradation of both biogenic compounds
      and anthropogenic contaminants. V. paradoxus also engages in mutually beneficial
      interactions with both bacteria and plants. The complete genome sequence of V.
      paradoxus S110 is composed of 6,754,997 bp with 6,279 predicted protein-coding
      sequences within two circular chromosomes. Genomic analysis has revealed multiple
      metabolic features for autotrophic and heterotrophic lifestyles. These metabolic
      diversities enable independent survival, as well as a symbiotic lifestyle.
      Consequently, S110 appears to have evolved into a superbly adaptable
      microorganism that is able to survive in ever-changing environmental conditions.
      Based on our findings, we suggest V. paradoxus S110 as a potential candidate for
      agrobiotechnological applications, such as biofertilizer and biopesticide.
      Because it has many associations with other biota, it is also suited to serve as
      an additional model system for studies of microbe-plant and microbe-microbe
      interactions.

PMID- 21183666
TI  - Escherichia coli exports cyclic AMP via TolC.
AB  - In Escherichia coli more than 180 genes are regulated by the cyclic AMP (cAMP)
      cAMP receptor protein (CRP) complex. However, more than 90% of cAMP that is made
      by intracellular adenylyl cyclases is found in the culture medium. How is cAMP
      exported from E. coli? In a tolC mutant, 0.03 mM IPTG (isopropyl-beta-d
      thiogalactopyranoside) was sufficient to induce beta-galactosidase compared to
      0.1 mM IPTG in the parent strain. In a cya mutant unable to produce cAMP about 1
      mM extracellular cAMP was required to induce beta-galactosidase, whereas in a cya
      tolC mutant 0.1 mM cAMP was sufficient. When cAMP in E. coli cya was generated
      intracellularly by a recombinant, weakly active adenylyl cyclase from
      Corynebacterium glutamicum, the critical level of cAMP necessary for induction of
      maltose degradation was only achieved in a tolC mutant and not in the parent
      strain. Deletion of a putative cAMP phosphodiesterase of E. coli, CpdA, resulted
      in a slightly similar, yet more diffuse phenotype. The data demonstrate that
      export of cAMP via TolC is a most efficient way of E. coli to lower high
      concentrations of cAMP in the cell and maintain its sensitivity in changing
      metabolic environments.

PMID- 21183667
TI  - PigS and PigP regulate prodigiosin biosynthesis in Serratia via differential
      control of divergent operons, which include predicted transporters of sulfur
      containing molecules.
AB  - Serratia sp. strain ATCC 39006 produces the red-pigmented antibiotic prodigiosin.
      Regulation of prodigiosin biosynthesis involves a complex hierarchy, with PigP a
      master transcriptional regulator of multiple genes involved in prodigiosin
      production. The focus of this study was a member of the PigP regulon, pigS, which
      encodes an ArsR/SmtB family transcriptional repressor. Mutations in pigS reduced
      production of prodigiosin by decreasing the transcription of the biosynthetic
      operon. The pigS gene is the first in a four-gene operon, which also encodes
      three membrane proteins (pmpABC) of the COG2391 (DUF395; YedE/YeeE) and COG0730
      (DUF81; TauE/SafE) families that we propose constitute transport components for
      sulfur-containing compounds. We provide the first experimental evidence
      confirming the membrane localization of a COG2391 protein, that of PmpB.
      Divergently transcribed from pigS-pmpABC is a bicistronic operon (blhA-orfY),
      which encodes a metallo-beta-lactamase and a coenzyme A-disulfide reductase
      containing a rhodanese homology domain, both of which may participate in
      reactions with sulfur-containing compounds. The overproduction of the BlhA and
      OrfY enzymes and the PmpABC membrane proteins differentially affected
      pigmentation. We have dissected the contributions of these various proteins and
      determined their importance in the control of prodigiosin production. PigS
      mediated control of prodigiosin occurred via binding directly to a short inverted
      repeat sequence in the intergenic region overlapping the predicted -10 regions of
      both pigS and blhA promoters and repressing transcription. PigP was required for
      the activation of these promoters, but only in the absence of PigS-mediated
      repression.

PMID- 21183669
TI  - How the xap locus put electrical "Zap" in Geobacter sulfurreducens biofilms.

PMID- 21183668
TI  - The chromosomal mazEF locus of Streptococcus mutans encodes a functional type II
      toxin-antitoxin addiction system.
AB  - Type II chromosomal toxin-antitoxin (TA) modules consist of a pair of genes that
      encode two components: a stable toxin and a labile antitoxin interfering with the
      lethal action of the toxin through protein complex formation. Bioinformatic
      analysis of Streptococcus mutans UA159 genome identified a pair of linked genes
      encoding a MazEF-like TA. Our results show that S. mutans mazEF genes form a
      bicistronic operon that is cotranscribed from a sigma70-like promoter.
      Overproduction of S. mutans MazF toxin had a toxic effect on S. mutans which can
      be neutralized by coexpression of its cognate antitoxin, S. mutans MazE. Although
      mazF expression inhibited cell growth, no cell lysis of S. mutans cultures was
      observed under the conditions tested. The MazEF TA is also functional in E. coli,
      where S. mutans MazF did not kill the cells but rather caused reversible cell
      growth arrest. Recombinant S. mutans MazE and MazF proteins were purified and
      were shown to interact with each other in vivo, confirming the nature of this TA
      as a type II addiction system. Our data indicate that MazF is a toxic nuclease
      arresting cell growth through the mechanism of RNA cleavage and that MazE
      inhibits the RNase activity of MazF by forming a complex. Our results suggest
      that the MazEF TA module might represent a cell growth modulator facilitating the
      persistence of S. mutans under the harsh conditions of the oral cavity.

PMID- 21183670
TI  - Genome sequence of poultry pathogen Riemerella anatipestifer strain RA-YM.
AB  - Riemerella anatipestifer is a Gram-negative, rod-shaped bacterium associated with
      epizootic infections in poultry. R. anatipestifer strain RA-YM, belonging to the
      serotype 1 prevalent in China, is a clinically isolated strain with high-level
      virulence. Here, we report the first genome sequence of this species.

PMID- 21183671
TI  - Genome sequence of Leuconostoc inhae KCTC 3774, isolated from Kimchi.
AB  - Leuconostoc inhae strain KCTC 3774 is a Gram-positive, non-spore-forming,
      heterofermentative, spherical or lenticular lactic acid bacterium. Here we
      announce the draft genome sequence of Leuconostoc inhae KCTC 3774, isolated from
      traditional Korean kimchi, and describe major findings from its annotation.

PMID- 21183672
TI  - Genome sequence of the zoonotic pathogen Chlamydophila psittaci.
AB  - We present the first genome sequence of Chlamydophila psittaci, an intracellular
      pathogen of birds and a human zoonotic pathogen. A comparison with previously
      sequenced Chlamydophila genomes shows that, as in other chlamydiae, most of the
      genome diversity is restricted to the plasticity zone. The C. psittaci plasmid
      was also sequenced.

PMID- 21183673
TI  - Target genes, consensus binding site, and role of phosphorylation for the
      response regulator MtrA of Corynebacterium glutamicum.
AB  - The two-component signal transduction system consisting of the sensor kinase MtrB
      and the response regulator MtrA is highly conserved in corynebacteria and
      mycobacteria. Whereas mtrA of Mycobacterium tuberculosis was reported to be
      essential, we recently succeeded in creating DeltamtrAB and DeltamtrA deletion
      mutants of Corynebacterium glutamicum and provided evidence that mepA and nlpC,
      both encoding putative cell wall peptidases, are directly repressed by MtrA,
      whereas proP and betP, both encoding carriers for compatible solutes, are
      directly activated by MtrA. In the present study, novel MtrA target genes were
      identified, including mepB, encoding another putative cell wall peptidase. The
      repressor or activator functions of MtrA correlate with the distance between the
      MtrA binding site and the transcriptional start site. From the identified binding
      sites within 20 target promoters, a 19-bp MtrA consensus motif was derived which
      represents a direct repeat of 8 base pairs separated by 3 base pairs. Gene
      expression of a strain containing MtrA with a D53N mutation instead of wild-type
      MtrA resembled that of a DeltamtrA mutant, indicating that MtrA is active in its
      phosphorylated form. This result was confirmed by electrophoretic mobility shift
      assays with phosphorylated MtrA which showed an increased binding affinity.

PMID- 21183674
TI  - Draft genome sequence of Turicibacter sanguinis PC909, isolated from human feces.
AB  - While the microbiota resident in the human gut is now known to provide a range of
      functions relevant to host health, many of the microbial members of the community
      have not yet been cultured or are represented by a limited number of isolates. We
      describe here the draft genome sequence of Turicibacter sanguinis PC909, isolated
      from a pooled healthy human fecal sample as part of the Australian Human Gut
      Microbiome Project.

PMID- 21183676
TI  - Complete genome of the plant growth-promoting rhizobacterium Pseudomonas putida
      BIRD-1.
AB  - We report the complete sequence of the 5.7-Mbp genome of Pseudomonas putida BIRD
      1, a metabolically versatile plant growth-promoting rhizobacterium that is highly
      tolerant to desiccation and capable of solubilizing inorganic phosphate and iron
      and of synthesizing phytohormones that stimulate seed germination and plant
      growth.

PMID- 21183675
TI  - Complete genome sequence of Algoriphagus sp. PR1, bacterial prey of a colony
      forming choanoflagellate.
AB  - Bacteria are the primary food source of choanoflagellates, the closest known
      relatives of animals. Studying signaling interactions between the Gram-negative
      Bacteroidetes bacterium Algoriphagus sp. PR1 and its predator, the
      choanoflagellate Salpingoeca rosetta, provides a promising avenue for testing
      hypotheses regarding the involvement of bacteria in animal evolution. Here we
      announce the complete genome sequence of Algoriphagus sp. PR1 and initial
      findings from its annotation.

PMID- 21183677
TI  - Genome sequence of the emerging pathogen Aeromonas caviae.
AB  - Aeromonas caviae is a Gram-negative, motile and rod-shaped facultative anaerobe
      that is increasingly being recognized as a cause of diarrhea in children. Here we
      present the first genome sequence of an A. caviae strain that was isolated as the
      sole pathogen from a child with profuse diarrhea.

PMID- 21183678
TI  - Viral double-stranded RNAs from vaccinia virus early or intermediate gene
      transcripts possess PKR activating function, resulting in NF-kappaB activation,
      when the K1 protein is absent or mutated.
AB  - PKR is a potent antiviral molecule that can terminate infection by inhibiting
      protein synthesis and stimulating NF-kappaB activation and apoptosis. Originally,
      it was thought that only intermediate and late gene transcription produced double
      stranded (ds) RNA to activate PKR during vaccinia virus (VACV) infection. The
      VACV E3 or K3 proteins squelch this effect by binding to either dsRNA or PKR.
      However, in the absence of the K1 protein, VACV infection activates PKR at very
      early times post-infection and despite the presence of E3 and K3. These data
      suggest that VACV infection induces PKR activation by a currently unknown
      mechanism. To determine this mechanism, cells were infected with K1L-containing
      or -deficient VACVs. By using conditions that limited the progression of the
      poxvirus replication cycle, we observed that early gene transcripts activated PKR
      in RK13 cells, identifying a new PKR-activating mechanism of poxvirus infection.
      Using a similar approach for HeLa cells, intermediate gene transcription was
      sufficient to activate PKR. RNA isolated from infected RK13 or HeLa cells
      maintained PKR-activating properties only when dsRNA was present. Moreover, viral
      dsRNA was directly detected in infected cells either by RT-PCR or
      immunofluorescent microscopy. Interestingly, dsRNA levels were higher in infected
      cells in which the K1 protein was nonfunctional. Only K1 proteins with PKR
      inhibitory function prevented downstream NF-kappaB activation. These results
      reveal a new PKR activation pathway during VACV infection, in which the K1
      protein reduces dsRNA levels early in VACV infection to directly inhibit PKR and
      several of its downstream antiviral effects, thereby enhancing virus survival.

PMID- 21183679
TI  - Disruption of the viral polymerase complex assembly as a novel approach to
      attenuate influenza A virus.
AB  - To develop a novel attenuation strategy applicable to all influenza A viruses, we
      targeted the highly conserved protein-protein interaction of the viral polymerase
      subunits PA and PB1. We postulated that impaired binding between PA and PB1 would
      negatively affect trimeric polymerase complex formation, leading to reduced viral
      replication efficiency in vivo. As proof of concept, we introduced single or
      multiple amino acid substitutions into the protein-protein-binding domains of
      either PB1 or PA, or both, to decrease binding affinity and polymerase activity
      substantially. As expected, upon generation of recombinant influenza A viruses
      (SC35M strain) containing these mutations, many pseudo-revertants appeared that
      partially restored PA-PB1 binding and polymerase activity. These polymerase
      assembly mutants displayed drastic attenuation in cell culture and mice. The
      attenuation of the polymerase assembly mutants was maintained in IFNalpha/beta
      receptor knock-out mice. As exemplified using a H5N1 polymerase assembly mutant,
      this attenuation strategy can be also applied to other highly pathogenic
      influenza A virus strains. Thus, we provide proof of principle that targeted
      mutation of the highly conserved interaction domains of PA and PB1 represents a
      novel strategy to attenuate influenza A viruses.

PMID- 21183680
TI  - Phosphorylation of caspase-8 (Thr-263) by ribosomal S6 kinase 2 (RSK2) mediates
      caspase-8 ubiquitination and stability.
AB  - The ribosomal S6 kinase 2 (RSK2) is a member of the p90 ribosomal S6 kinase
      (p90RSK) family of proteins and plays a critical role in proliferation, cell
      cycle, and cell transformation. Here, we report that RSK2 phosphorylates caspase
      8, and Thr-263 was identified as a novel caspase-8 phosphorylation site. In
      addition, we showed that EGF induces caspase-8 ubiquitination and degradation
      through the proteasome pathway, and phosphorylation of Thr-263 is associated with
      caspase-8 stability. Finally, RSK2 blocks Fas-induced apoptosis through its
      phosphorylation of caspase-8. These data provide a direct link between RSK2 and
      caspase-8 and identify a novel molecular mechanism for caspase-8 modulation by
      RSK2.

PMID- 21183681
TI  - Improvement of dolichol-linked oligosaccharide biosynthesis by the squalene
      synthase inhibitor zaragozic acid.
AB  - The majority of congenital disorders of glycosylation (CDG) are caused by defects
      of dolichol (Dol)-linked oligosaccharide assembly, which lead to under-occupancy
      of N-glycosylation sites. Most mutations encountered in CDG are hypomorphic, thus
      leaving residual activity to the affected biosynthetic enzymes. We hypothesized
      that increased cellular levels of Dol-linked substrates might compensate for the
      low biosynthetic activity and thereby improve the output of protein N
      glycosylation in CDG. To this end, we investigated the potential of the squalene
      synthase inhibitor zaragozic acid A to redirect the flow of the polyisoprene
      pathway toward Dol by lowering cholesterol biosynthesis. The addition of
      zaragozic acid A to CDG fibroblasts with a Dol-P-Man synthase defect led to the
      formation of longer Dol-P species and to increased Dol-P-Man levels. This
      treatment was shown to decrease the pathologic accumulation of incomplete Dol
      pyrophosphate-GlcNAc(2)Man(5) in Dol-P-Man synthase-deficient fibroblasts.
      Zaragozic acid A treatment also decreased the amount of truncated protein N
      linked oligosaccharides in these CDG fibroblasts. The increased cellular levels
      of Dol-P-Man and possibly the decreased cholesterol levels in zaragozic acid A
      treated cells also led to increased availability of the
      glycosylphosphatidylinositol anchor as shown by the elevated cell-surface
      expression of the CD59 protein. This study shows that manipulation of the
      cellular Dol pool, as achieved by zaragozic acid A addition, may represent a
      valuable approach to improve N-linked glycosylation in CDG cells.

PMID- 21183683
TI  - RNA sequences and structures required for the recruitment and activity of the
      dengue virus polymerase.
AB  - Dengue virus RNA-dependent RNA polymerase specifically binds to the viral genome
      by interacting with a promoter element known as stem-loop A (SLA). Although a
      great deal has been learned in recent years about the function of this promoter
      in dengue virus-infected cells, the molecular details that explain how the SLA
      interacts with the polymerase to promote viral RNA synthesis remain poorly
      understood. Using RNA binding and polymerase activity assays, we defined two
      elements of the SLA that are involved in polymerase interaction and RNA
      synthesis. Mutations at the top of the SLA resulted in RNAs that retained the
      ability to bind the polymerase but impaired promoter-dependent RNA synthesis.
      These results indicate that protein binding to the SLA is not sufficient to
      induce polymerase activity and that specific nucleotides of the SLA are necessary
      to render an active polymerase-promoter complex for RNA synthesis. We also report
      that protein binding to the viral RNA induces conformational changes downstream
      of the promoter element. Furthermore, we found that structured RNA elements at
      the 3' end of the template repress dengue virus polymerase activity in the
      context of a fully active SLA promoter. Using assays to evaluate initiation of
      RNA synthesis at the viral 3'-UTR, we found that the RNA-RNA interaction mediated
      by 5'-3'-hybridization was able to release the silencing effect of the 3'-stem
      loop structure. We propose that the long range RNA-RNA interactions in the viral
      genome play multiple roles during RNA synthesis. Together, we provide new
      molecular details about the promoter-dependent dengue virus RNA polymerase
      activity.

PMID- 21183682
TI  - Fas-associated death domain (FADD) and the E3 ubiquitin-protein ligase TRIM21
      interact to negatively regulate virus-induced interferon production.
AB  - The production of cytokines such as type I interferon (IFN) is an essential
      component of innate immunity. Insufficient amounts of cytokines lead to host
      sensitivity to infection, whereas abundant cytokine production can lead to
      inflammation. A tight regulation of cytokine production is, thus, essential for
      homeostasis of the immune system. IFN-alpha production during RNA virus infection
      is mediated by the master transcription factor IRF7, which is activated upon
      ubiquitination by TRAF6 and phosphorylation by IKKepsilon and TBK1 kinases. We
      found that Fas-associated death domain (FADD), first described as an apoptotic
      protein, is involved in regulating IFN-alpha production through a novel
      interaction with TRIM21. TRIM21 is a member of a large family of proteins that
      can impart ubiquitin modification onto its cellular targets. The interaction
      between FADD and TRIM21 enhances TRIM21 ubiquitin ligase activity, and together
      they cooperatively repress IFN-alpha activation in Sendai virus-infected cells.
      FADD and TRIM21 can directly ubiquitinate IRF7, affect its phosphorylation
      status, and interfere with the ubiquitin ligase activity of TRAF6. Conversely, a
      reduction of FADD and TRIM21 levels leads to higher IFN-alpha induction, IRF7
      phosphorylation, and lower titers of RNA virus of infected cells. We conclude
      that FADD and TRIM21 together negatively regulate the late IFN-alpha pathway in
      response to viral infection.

PMID- 21183684
TI  - Single molecule studies of physiologically relevant telomeric tails reveal POT1
      mechanism for promoting G-quadruplex unfolding.
AB  - Human telomeres are composed of duplex TTAGGG repeats and a 3' single-stranded
      DNA tail. The telomeric DNA is protected and regulated by the shelterin proteins,
      including the protection of telomeres 1 (POT1) protein that binds telomeric
      single-stranded DNA. The single-stranded tail can fold into G-quadruplex (G4)
      DNA. Both POT1 and G4 DNA play important roles in regulating telomere length
      homeostasis. To date, most studies have focused on individual quadruplexes formed
      by four TTAGGG repeats. Telomeric tails in human cells have on average six times
      as many repeats, and no structural studies have examined POT1 binding in
      competition with G4 DNA folding. Using single molecule atomic force microscopy
      imaging, we observed that the majority of the telomeric tails of 16 repeats
      formed two quadruplexes even though four were possible. The result that
      physiological telomeric tails rarely form the maximum potential number of G4
      units provides a structural basis for the coexistence of G4 and POT1 on the same
      DNA molecule, which is observed directly in the captured atomic force microscopy
      images. We further observed that POT1 is significantly more effective in
      disrupting quadruplex DNA on long telomeric tails than an antisense
      oligonucleotide, indicating a novel POT1 activity beyond simply preventing
      quadruplex folding.

PMID- 21183685
TI  - Ubiquitination regulates the internalization, endolysosomal sorting, and
      signaling of the erythropoietin receptor.
AB  - Ubiquitination is a common mechanism of down-regulation of mitogenic receptors.
      Here, we show that ubiquitination of the erythropoietin receptor (EpoR) at
      Lys(256) is necessary and sufficient for efficient Epo-induced receptor
      internalization, whereas ubiquitination at Lys(428) promotes trafficking of
      activated receptors to the lysosomes for degradation. Interestingly, EpoR that
      cannot be ubiquitinated has reduced mitogenic activities and ability to stimulate
      the STAT5, Ras/MAPK, and PI3K/AKT signaling pathways. We therefore propose that
      ubiquitination of the EpoR critically controls both receptor down-regulation and
      downstream signaling.

PMID- 21183686
TI  - Double-stranded DNA binding domain of poly(ADP-ribose) polymerase-1 and molecular
      insight into the regulation of its activity.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) modifies various proteins, including
      itself, with ADP-ribose polymers (automodification). Polymer synthesis is
      triggered by binding of its zinc finger 1 (Zn1) and 2 (Zn2) to DNA breaks and is
      followed by inactivation through automodification. The multiple functional
      domains of PARP-1 appear to regulate activation and automodification-mediated
      inactivation of PARP-1. However, the roles of these domains in activation
      inactivation processes are not well understood. Our results suggest that Zn1,
      Zn2, and a domain identified in this study, the double-stranded DNA binding
      (DsDB) domain, are involved in DNA break-dependent activation of PARP-1. We found
      that binding of the DsDB domain to double-stranded DNA and DNA break recognition
      by Zn1 and Zn2, whose actual binding targets are likely to be single-stranded
      DNA, lead to the activation of PARP-1. In turn, the displacement of single- and
      double-stranded DNA from Zn2 and the DsDB domain caused by ADP-ribose polymer
      synthesis results in the dissociation of PARP-1 from DNA breaks and thus its
      inactivation. We also found that the WGR domain is one of the domains involved in
      the RNA-dependent activation of PARP-1. Furthermore, because zinc finger 3 (Zn3)
      has the ability to bind to single-stranded RNA, it may have an indirect role in
      RNA-dependent activation. PARP-1 functional domains, which are involved in
      oligonucleic acid binding, therefore coordinately regulate PARP-1 activity
      depending on the status of the neighboring oligonucleic acids. Based on these
      results, we proposed a model for the regulation of PARP-1 activity.

PMID- 21183687
TI  - Regulation of histone H2A and H2B deubiquitination and Xenopus development by
      USP12 and USP46.
AB  - Post-translational histone modifications play important roles in regulating gene
      expression programs, which in turn determine cell fate and lineage commitment
      during development. One such modification is histone ubiquitination, which
      primarily targets histone H2A and H2B. Although ubiquitination of H2A and H2B has
      been generally linked to gene silencing and gene activation, respectively, the
      functions of histone ubiquitination during eukaryote development are not well
      understood. Here, we identified USP12 and USP46 as histone H2A and H2B
      deubiquitinases that regulate Xenopus development. USP12 and USP46 prefer
      nucleosomal substrates and deubiquitinate both histone H2A and H2B in vitro and
      in vivo. WDR48, a WD40 repeat-containing protein, interacts with USP12 and USP46
      and is required for the histone deubiquitination activity. Overexpression of
      either gene leads to gastrulation defects without affecting mesodermal cell fate,
      whereas knockdown of USP12 in Xenopus embryos results in reduction of a subset of
      mesodermal genes at gastrula stages. Immunohistochemical staining and chromatin
      immunoprecipitation assays revealed that USP12 regulates histone deubiquitination
      in the mesoderm and at specific gene promoters during Xenopus development. Taken
      together, this study identifies USP12 and USP46 as histone deubiquitinases for
      H2A and H2B and reveals that USP12 regulates Xenopus development during gastrula
      stages.

PMID- 21183688
TI  - Spread of the qnrVC quinolone resistance determinant in Vibrio cholerae.

PMID- 21183689
TI  - Endothelial reticulon-4B (Nogo-B) regulates ICAM-1-mediated leukocyte
      transmigration and acute inflammation.
AB  - The reticulon (Rtn) family of proteins are localized primarily to the endoplasmic
      reticulum (ER) of most cells. The Rtn-4 family, (aka Nogo) consists of 3 splice
      variants of a common gene called Rtn-4A, Rtn-4B, and Rtn-4C. Recently, we
      identified the Rtn-4B (Nogo-B) protein in endothelial and smooth muscle cells of
      the vessel wall, and showed that Nogo-B is a regulator of cell migration in vitro
      and vascular remodeling and angiogenesis in vivo. However, the role of Nogo-B in
      inflammation is still largely unknown. In the present study, we use 2 models of
      inflammation to show that endothelial Nogo-B regulates leukocyte transmigration
      and intercellular adhesion molecule-1 (ICAM-1)-dependent signaling. Mice lacking
      Nogo-A/B have a marked reduction in neutrophil and monocyte recruitment to sites
      of inflammation, while Nogo-A/B(-/-) mice engrafted with wild-type (WT) bone
      marrow still exhibit impaired inflammation compared with WT mice engrafted with
      Nogo-A/B(-/-) bone marrow, arguing for a critical role of host Nogo in this
      response. Using human leukocytes and endothelial cells, we show mechanistically
      that the silencing of Nogo-B with small interfering RNA (siRNA) impairs the
      transmigration of neutrophils and reduces ICAM-1-stimulated phosphorylation of
      vascular endothelial-cell cadherin (VE-cadherin). Our results reveal a novel role
      of endothelial Nogo-B in basic immune functions and provide a key link in the
      molecular network governing endothelial-cell regulation of diapedesis.

PMID- 21183692
TI  - A new guise for hyper-IgM syndrome.

PMID- 21183691
TI  - Involvement of an alternative oxidase in oxidative stress and mycelium-to-yeast
      differentiation in Paracoccidioides brasiliensis.
AB  - Paracoccidioides brasiliensis is a thermodimorphic human pathogenic fungus that
      causes paracoccidioidomycosis (PCM), which is the most prevalent systemic mycosis
      in Latin America. Differentiation from the mycelial to the yeast form (M-to-Y) is
      an essential step for the establishment of PCM. We evaluated the involvement of
      mitochondria and intracellular oxidative stress in M-to-Y differentiation. M-to-Y
      transition was delayed by the inhibition of mitochondrial complexes III and IV or
      alternative oxidase (AOX) and was blocked by the association of AOX with complex
      III or IV inhibitors. The expression of P. brasiliensis aox (Pbaox) was
      developmentally regulated through M-to-Y differentiation, wherein the highest
      levels were achieved in the first 24 h and during the yeast exponential growth
      phase; Pbaox was upregulated by oxidative stress. Pbaox was cloned, and its
      heterologous expression conferred cyanide-resistant respiration in Saccharomyces
      cerevisiae and Escherichia coli and reduced oxidative stress in S. cerevisiae
      cells. These results reinforce the role of PbAOX in intracellular redox balancing
      and demonstrate its involvement, as well as that of other components of the
      mitochondrial respiratory chain complexes, in the early stages of the M-to-Y
      differentiation of P. brasiliensis.

PMID- 21183693
TI  - Chemical genomics and combo therapy.

PMID- 21183690
TI  - The small GTPase RacA mediates intracellular reactive oxygen species production,
      polarized growth, and virulence in the human fungal pathogen Aspergillus
      fumigatus.
AB  - Aspergillus fumigatus is the predominant mold pathogen in immunocompromised
      patients. In this study, we present the first characterization of the small
      GTPase RacA in A. fumigatus. To gain insight into the function of racA in the
      growth and pathogenesis of A. fumigatus, we constructed a strain that lacks a
      functional racA gene. The DeltaracA strain showed significant morphological
      defects, including a reduced growth rate and abnormal conidiogenesis on glucose
      minimal medium. In the DeltaracA strain, apical dominance in the leading hyphae
      is lost and, instead, multiple axes of polarity emerge. Intriguingly, superoxide
      production at the hyphal tips was reduced by 25% in the DeltaracA strain.
      Treatment of wild-type hyphae with diphenylene iodonium, an inhibitor of NADPH
      oxidase, resulted in phenotypes similar to that of the DeltaracA strain. These
      data suggest that DeltaracA strain phenotypes may be due to a reduction or
      alteration in the production of reactive oxygen species. Most surprisingly,
      despite these developmental and growth abnormalities, the DeltaracA strain
      retained at least wild-type virulence in both an insect model and two
      immunologically distinct murine models of invasive pulmonary aspergillosis. These
      results demonstrate that in vitro growth phenotypes do not always correlate with
      in vivo virulence and raise intriguing questions about the role of RacA in
      Aspergillus virulence.

PMID- 21183694
TI  - Pin-ing down PMN priming.

PMID- 21183695
TI  - The "age" of understanding VKA dose.

PMID- 21183696
TI  - Crohn disease: remissions but no cure.

PMID- 21183697
TI  - Vascular balancing act: EGFL7 and Notch.

PMID- 21183698
TI  - Polymorphisms in the multidrug resistance gene MDR1 (ABCB1) predict for molecular
      resistance in patients with newly diagnosed chronic myeloid leukemia receiving
      high-dose imatinib.

PMID- 21183699
TI  - Elevated circulating t(14;18) translocation levels prior to diagnosis of
      follicular lymphoma.

PMID- 21183700
TI  - The prognostic value of multilineage dysplasia in de novo acute myeloid leukemia
      patients with intermediate-risk cytogenetics is dependent on NPM1 mutational
      status.

PMID- 21183701
TI  - Platelet secretion defect in patients with familial hemophagocytic
      lymphohistiocytosis type 5 (FHL-5).

PMID- 21183702
TI  - Platelet interior imaging technologies.

PMID- 21183704
TI  - Form, function, and regulation of ARGONAUTE proteins.
AB  - Both transcriptional (TGS) and posttranscriptional gene silencing (PTGS) are
      conserved eukaryotic gene regulatory mechanisms, integral for taming exogenous
      (viruses and bacteria) or endogenous (repetitive elements and transposons)
      invasive nucleic acids to minimize their impact on genome integrity and function.
      TGS and PTGS also are essential for controlling the expression of protein coding
      genes throughout development or in response to environmental stimuli. In plants
      and animals, at least one member of the conserved ARGONAUTE (AGO) protein family
      comprises the catalytic engine of the silencing complex, which is guided by
      sequence-specific small RNA to cognate RNA. In this review, we present general
      features of plant and animal AGO proteins and detail our knowledge on the 10
      Arabidopsis thaliana AGOs.

PMID- 21183707
TI  - Amylin may offer (more) help to treat postmenopausal obesity.

PMID- 21183706
TI  - TCP transcription factors link the regulation of genes encoding mitochondrial
      proteins with the circadian clock in Arabidopsis thaliana.
AB  - Diurnal regulation of transcripts encoding proteins located in mitochondria,
      plastids, and peroxisomes is important for adaptation of organelle biogenesis and
      metabolism to meet cellular requirements. We show this regulation is related to
      diurnal changes in promoter activities and the presence of specific cis-acting
      regulatory elements in the proximal promoter region [TGGGC(C/T)], previously
      defined as site II elements, and leads to diurnal changes in organelle protein
      abundances. These site II elements can act both as activators or repressors of
      transcription, depending on the night/day period and on the number and
      arrangement of site II elements in the promoter tested. These elements bind to
      the TCP family of transcriptions factors in Arabidopsis thaliana, which nearly
      all display distinct diurnal patterns of cycling transcript abundance. TCP2,
      TCP3, TCP11, and TCP15 were found to interact with different components of the
      core circadian clock in both yeast two-hybrid and direct protein-protein
      interaction assays, and tcp11 and tcp15 mutant plants showed altered transcript
      profiles for a number of core clock components, including LATE ELONGATED
      HYPOCOTYL1 and PSEUDO RESPONSE REGULATOR5. Thus, site II elements in the promoter
      regions of genes encoding mitochondrial, plastid, and peroxisomal proteins
      provide a direct mechanism for the coordination of expression for genes involved
      in a variety of organellar functions, including energy metabolism, with the time
      of-day specific needs of the organism.

PMID- 21183708
TI  - Relative contributions of animal and muscle effects to variation in beef lean
      color stability.
AB  - Muscles from beef carcasses (n = 100) were selected from a commercial processor
      and aged for 14 d. Longissimus lumborum (LL), semimembranosus (SM), biceps
      femoris (BF), gluteus medius (GM), triceps brachii (TB), rectus femoris, vastus
      lateralis, adductor, semitendinosus, infraspinatus, teres major, biceps femoris
      ischiatic head, biceps femoris sirloin cap, and gracillus steaks were placed in
      display for 9 d. Instrumental color variables [lightness (L*), redness (a*),
      yellowness (b*), hue angle, chroma, and overall color change from d 0 (E)] were
      determined on d 0, 1, 3, 6, and 9 of display. Muscle pH and myoglobin content
      were determined for LL, SM, BF, GM, and TB. Muscles differed (P < 0.05) in
      initial values of each color variable evaluated, and the extent and timing of
      changes during display differed across muscles. Relationships between color
      variables measured in LL steaks and those measured in steaks from other muscles
      differed across days of display with the strongest relationships being observed
      earlier in the display period for labile muscles and later in stable muscles.
      Lightness of LL steaks was correlated with lightness of all of other muscles
      evaluated, regardless of display day (r = 0.27 to 0.79). For a*, hue angle,
      chroma, and E values, the strongest relationships between LL values and those of
      other muscles were detected between d 9 LL values and those of other muscles on d
      3, 6, or 9, depending on the relative stability of the muscle. Correlation
      coefficients between d 9 a*, hue angle, chroma, and E values in LL and those of
      other muscles were 0.50, 0.65, 0.28, and 0.43 (P < 0.05) or greater,
      respectively, for the muscles included in the study. Myoglobin content of SM, BF,
      GM, and TB was highly correlated with that of LL (r = 0.83, 0.82, 0.72, and 0.67,
      respectively; P < 0.05). Muscle pH of LL was correlated with pH of SM and GM (r =
      0.44 and 0.53; P < 0.05), but not (P > 0.05) pH of BF or TB. Muscle effects
      generally explained more variation in a*, b*, hue angle, chroma, and E than
      animal effects. However, the relative importance of animal effects increased as
      display continued. These data indicate that animal effects were consistent across
      muscles, though muscle effects had greater contribution to color stability
      variation. Furthermore, strong relationships between LL color stability and the
      stability of other muscles indicate that strategies developed to manage animal
      variation in LL color stability would beneficially affect the entire carcass.

PMID- 21183709
TI  - Developmental factors that influence sow longevity.
AB  - The length of adult sow life is now recognized as both an economic and a welfare
      concern. However, there are no consistent definitions to measure sow longevity.
      This study assessed 6 different descriptions of longevity and determined their
      relationship with developmental performance factors. Longevity definitions
      included stayability (probability of a sow producing 40 pigs or probability of
      her reaching 4 parities), lifespan (number of parities a female has accumulated
      before culling), lifetime prolificacy (number of pigs born alive during the
      productive lifetime of a female), herd life (time from first farrowing to
      culling), and pigs produced per day of life. Data consisted of 14,262 records of
      Yorkshire females from both nucleus and multiplication herds across 21 farms from
      4 seedstock systems. Within a subset of the data, information was available on
      the litter birth record of the female and her growth and composition data.
      Therefore, data were subdivided into 2 data sets, consisting of 1) data A, data
      from the farrowing records of a female, and 2) data B, data A and information
      from the litter birth record of a female and the growth and backfat data from a
      female. A Cox proportional hazards model was used to determine the relationship
      of developmental factors and first farrowing record with longevity. Those factors
      that were significantly (P < 0.0001) associated with longevity, regardless of
      definition, were age at first farrowing, litter size at first farrowing and last
      farrowing, number of stillborn in the first litter, adjusted 21-d litter weight
      of the first litter, herd type, backfat, and growth. Within a contemporary group,
      fatter, slower growing gilts had a decreased risk of being culled. Additionally,
      sows that had more pigs born alive, fewer stillborn pigs, and heavier litters at
      21 d of lactation in their first litter had a decreased risk of being culled.
      Furthermore, sows from nucleus herds experienced a greater risk of being culled.
      Many factors affected longevity, regardless of definition. Pork producers can
      implement management protocols that can extend the productive life of breeding
      females, resulting in improved profitability and animal welfare.

PMID- 21183710
TI  - Effects of genetic markers and implant strategy on longissimus and gluteus muscle
      tenderness of calf-fed steers and heifers.
AB  - Effects of genotype (GEN) and implant program (IMP) on LM and gluteus muscle (GM)
      tenderization were investigated using crossbred steer (n = 185) and heifer (n =
      158) calves. The 3-marker GeneSTAR Tenderness panel [CAST (calpastatin), CAPN1
      316 (u-calpain), and CAPN1 4751 (u-calpain)] was used to determine the GEN of
      each animal (reported as total number of favorable alleles, 0 through 6). Calves
      were randomly assigned to 1 of 2 IMP, conventional (CNV) or delayed. Cattle in
      the CNV group were implanted at the beginning of the finishing period with
      Revalor-IS or Revalor-IH (Intervet Inc., Millsboro, DE), and then reimplanted 59
      d later with Revalor-S or Revalor-H (Intervet Inc.). Calves in the delayed group
      received a single terminal implant (Revalor-S or Revalor-H) administered 45 d
      after initiation of the finishing period. Warner-Bratzler shear force (WBSF) was
      measured on LM and GM steaks at 3, 7, 14, 21, and 28 d postmortem. No
      interactions between the main effects of sex, IMP, or GEN were detected (P >
      0.05) for WBSF. An IMP * postmortem aging (age) interaction was detected (P <
      0.05) for LM and GM WBSF. For both muscles, steaks from CNV cattle had WBSF
      values that were approximately 0.2 kg greater (P < 0.05) than the values for
      steaks from delayed animals, but only during the early postmortem period (3 to 7
      d). A linear effect of GEN on WBSF was detected (P < 0.05) for LM and GM steaks.
      Within each muscle, steaks from cattle with 6 favorable alleles had WBSF values
      0.33 kg less than the values for steaks from cattle with 1 favorable allele. The
      GEN * age interaction was not significant for LM (P = 0.14) or GM (P = 0.20), but
      a numerical trend was observed for the effect of GEN on WBSF to diminish as age
      increased. To investigate how genetic markers could be interfaced with current
      beef carcass quality grading, cattle were sorted into 2 gene marker groups (GMG),
      <=3 vs. >=4 favorable alleles. For both muscles, GMG was effective only at
      identifying tenderness differences within the Select grade. When aged <=14 d,
      Select LM steaks from cattle with >=4 alleles had smaller (P < 0.05) WBSF values
      than did LM steaks from animals with <=3 alleles. Preslaughter factors (sex, IMP,
      and GMG) controlled in the present study each accounted for less than 7% of the
      explained variation in tenderness of the test population. Results from this study
      suggest that the 3 GeneSTAR Tenderness markers were associated with small
      differences (0.33 kg) in WBSF and may be useful for increasing the consistency of
      Select beef, but these specific markers accounted for only a minor amount of
      variation in beef tenderness.

PMID- 21183711
TI  - Texture and acceptability of goat meat frankfurters processed with 3 different
      sources of fat.
AB  - The objective of this research was to evaluate the texture and consumer
      acceptability of goat meat frankfurter formulations with no added fat (NAF), beef
      fat (BF), or canola oil (CO). Consumer sensory evaluation, fat, and moisture and
      texture profile analyses were performed on goat meat frankfurters produced with
      the fat sources BF, CO, and NAF. For sensory evaluations, NAF was less tender (P
      = 0.007; 4.90 vs. 4.11 and 4.35 for BF and CO, respectively) and the flavor was
      liked less (P = 0.004; 4.59 vs. 3.83 and 4.30 for BF and CO, respectively); BF
      was scored as the juiciest (P = 0.003; 3.86 vs. 4.49 and 4.58 for CO and NAF,
      respectively); and CO had the least amount of flavor (P = 0.029; 3.65 vs. 3.12
      and 3.10 for BF and NAF, respectively). Moisture was least (P < 0.001) in CO
      (46.59%), followed by BF (48.57%) and NAF (55.80%). The amount of fat was not
      different (P = 0.761) in BF (24.36%) or CO (24.43%) but was less (P < 0.001) in
      NAF (9.06%), as expected. The NAF had the most protein (P < 0.001; 34.14%),
      followed by CO (27.98%) and BF (26.07%). For texture profile analyses, NAF had
      the least hardness value (P = 0.008; 3.92 vs. 4.48 and 4.40 for BF and CO,
      respectively) and least chewiness value (P = 0.026; 2.89 vs. 3.39 and 3.29 for BF
      and CO, respectively). Beef fat and CO were not different for hardness (P =
      0.596) or chewiness (P = 0.530). No differences were observed in springiness (P =
      0.954) or resilience (P = 0.561). The sensory panelists tended to prefer BF for
      overall acceptability. Results from these data revealed that value-added goat
      meat products received acceptable sensory scores; therefore, continued research
      and development will greatly expand the knowledge of goat meat and increase the
      acceptance of value-added products.

PMID- 21183712
TI  - Head-only followed by cardiac arrest electrical stunning is an effective
      alternative to head-only electrical stunning in pigs.
AB  - Many small slaughter facilities use head-only electrical stunning to render swine
      unconscious and insensible to pain before slaughter. Head-only electrical
      stunning is a reversible procedure that is optimally effective for approximately
      15 s after stun completion. In many small North American slaughter plants, the
      authors have observed hoist speeds that are too slow to achieve a short enough
      stun-to-bleed interval to maintain insensibility through exsanguination. Unlike
      many European plants, there is no separate high-speed hoist for pigs and
      exsanguination on the floor is not condoned. As a result, a 2-stage stunning
      method was proposed where head-only stunning for 3 s was immediately followed by
      application of the same stunning wand to the cardiac region of the animal for 3 s
      while lying in lateral recumbancy. A paired-comparison study was conducted on 89
      pigs in a small slaughter facility to compare the head-only method applied for 6
      s with the head/heart method. The objective was to evaluate signs of return to
      sensibility, stun-to-bleed time, blood lactate concentration, muscle pH, drip
      loss, and fresh meat color to validate the head/heart electrical stunning method
      for small slaughter plants. Incidence of corneal reflex was not different (P >
      0.05) between head/heart (93.8%) and head only (85%) stunning. Nose twitching was
      more common (P < 0.05) in head only (26.5%) than head/heart (5%) stunning.
      Head/heart stunning eliminated rhythmic breathing, natural blinking, eye tracking
      to moving objects, and righting reflex, which were all observed in head-only
      stunned pigs. Eye tracking to moving objects was observed in 40.8% of head-only
      stunned pigs. Blood lactate was not different (P > 0.05) between stunning methods
      (head only: 8.8 +/- 0.7 mmol/L, head/heart: 7.8 +/- 0.7 mmol/L). Stun-to-bleed
      time did not differ (P > 0.05; head only: 32 +/- 1 s, head/heart: 33 +/- 1 s).
      Mean time to loss of heartbeat with the head-only method was 121 +/- 5 s. No
      heartbeat was observed with the head/heart method. Longissimus thoracis pH,
      color, and drip loss were not different (P > 0.05) between stunning methods. This
      study determined that the head/heart electrical stunning method reduces the
      incidence of signs of return to sensibility without significant effects on meat
      quality, plant operation speed, or blood lactate concentration. In addition, the
      head/heart method requires no capital investment for plants that are currently
      using the head-only method.

PMID- 21183713
TI  - Single nucleotide polymorphisms in the growth hormone-insulin-like growth factor
      axis in straightbred and crossbred Angus, Brahman, and Romosinuano heifers:
      population genetic analyses and association of genotypes with reproductive
      phenotypes.
AB  - The growth endocrine axis influences reproduction. The objectives of this study
      were to evaluate population genetic characteristics of SNP genotypes within genes
      of the GH-IGF axis in straightbred and crossbred Angus, Brahman, and Romosinuano
      heifers (n = 650) and to test the association of these genotypes with measures of
      reproduction. These objectives were achieved using 73 SNP within 7 genes on
      chromosome 5 and the pregnancy-associated plasma protein A2 (PAPP-A2) and GH
      receptor genes, which map to chromosomes 16 and 20, respectively. The SNP were
      elucidated by resequencing conserved regions of each gene by using DNA from
      familial-unrelated cattle of a multibreed discovery population. A multiplex SNP
      assay yielded 59 biallelic SNP useful for evaluating genetic identity and
      distance. Specifically, the divergence of straightbred Brahman cattle was
      approximately 15.5% from 5 Bos taurus-influenced breed groups. In the
      straightbred groups used as a validation population, only 3 SNP had minor allele
      frequencies >10%. These SNP were in the genes PAPP-A2 (ss115492449-A/C and
      ss115492450-G/T within intron 10) and signal transducers and activators of
      transcription 2 (STAT2; ss252841035-A/G within the 5' untranslated region), and
      they met the conditions of Hardy-Weinberg equilibrium (P > 0.31). The other 56
      SNP were useful for assigning each animal into ancestral clusters (n = 3
      proportions) to account for population stratification in genotype to phenotype
      association analyses. The 2 SNP in the PAPP-A2 gene influenced (P < 0.05) traits
      indicative of first-calf heifer rebreeding (i.e., calving interval, days to
      calving, and pregnancy rate). A STAT2 SNP genotype (i.e., GG) * primary ancestral
      cluster interaction (P < 0.05) suggested heifers primarily of B. taurus ancestry
      had a reduction of approximately 16.4 +/- 0.1% in calving interval and days to
      calving relative to heifers clustering primarily as Bos indicus ancestry. Even
      though additional research is needed to delineate the allelic variation
      attributed to genes of the GH-IGF axis, results of this study provide support for
      STAT2 and PAPP-A2 as potential candidate genes associated with first-calf heifer
      rebreeding traits.

PMID- 21183714
TI  - Physiology and endocrinology symposium: sperm-oviduct interactions in livestock
      and poultry.

PMID- 21183715
TI  - Whole-genome association analyses for lifetime reproductive traits in the pig.
AB  - Profits for commercial pork producers vary in part because of sow productivity or
      sow productive life (SPL) and replacement costs. During the last decade, culling
      rates of sows have increased to more than 50% in the United States. Both SPL and
      culling rates are influenced by genetic and nongenetic factors. A whole-genome
      association study was conducted for pig lifetime reproductive traits, including
      lifetime total number born (LTNB), lifetime number born alive (LNBA), removal
      parity, and the ratio between lifetime nonproductive days and herd life. The
      proportion of phenotypic variance explained by markers was 0.15 for LTNB and
      LNBA, 0.12 for removal parity, and 0.06 for the ratio between lifetime
      nonproductive days and herd life. Several informative QTL regions (e.g., 14 QTL
      regions for LTNB) and genes within the regions (e.g., SLC22A18 on SSC2 for LTNB)
      were associated with lifetime reproductive traits in this study. Genes associated
      with LTNB and LNBA were similar, reflecting the high genetic correlation (0.99 +/
      0.003) between these traits. Functional annotation revealed that many genes at
      the associated regions are expressed in reproductive tissues. For instance, the
      SLC22A18 gene on SSC2 associated with LTNB has been shown to be expressed in the
      placenta of mice. Many of the QTL regions showing associations coincided with
      previously identified QTL for fat deposition. This reinforces the role of fat
      regulation for lifetime reproductive traits. Overall, this whole-genome
      association study provides a list of genomic locations and markers associated
      with pig lifetime reproductive traits that could be considered for SPL in future
      studies.

PMID- 21183716
TI  - Relationship between hot flashes and ambulatory blood pressure: the Hilo women's
      health study.
AB  - OBJECTIVES: To examine ambulatory blood pressure (BP) differences between women
      who report hot flashes (HFs) and those who do not, and to observe whether an
      objectively measured HF is associated with transient changes in BP. HFs have been
      associated with elevated BP, but studies have not examined the relationship
      between objectively measured HFs and blood pressure during normal daily
      activities. METHODS: A sample of 202 women in Hilo, Hawaii, aged 45 to 55 years,
      were asked to fill out a questionnaire that included demographic information and
      an inventory of symptoms. The women underwent simultaneous 24-hour monitoring of
      ambulatory BP and HFs, at the same time keeping a diary that included mood and HF
      reports. RESULTS: No significant difference was present in mean BP between women
      who reported having an HF during the last 2 weeks and those who did not. When
      measurements controlled for negative mood reports and posture, there was a highly
      significant elevation in Z scores of systolic BP when a measured, objective HF
      occurred within 10 minutes before a BP reading, and a significant elevation of Z
      scores of diastolic BP when a subjectively reported HF occurred within 10 minutes
      after a BP reading. CONCLUSIONS: These results suggest that objectively measured
      HFs precede transient elevations of systolic BP, but it is unclear if there is a
      causal relationship. These results also suggest that women experience subjective
      HFs within 10 minutes after a transient increase in diastolic BP. Again, the
      causal relationship is not understood.

PMID- 21183717
TI  - Changes in ventricular repolarization duration during typical daily emotion in
      patients with Long QT syndrome.
AB  - OBJECTIVE: Intense emotions are known triggers of sudden cardiac death. However,
      the effect of typical daily emotion on repolarization has not been examined. We
      examined whether QT interval changes as a function of typical daily emotion in
      patients at risk for cardiac events in the context of emotion. METHODS: We
      studied 161 patients (n = 114 females; mean age, 35 years) with the congenital
      form of the Long QT Syndrome during daily activities. Each day for 3 days, a 12
      hour Holter recording was completed. Patients were paged ten times per day at
      random times and rated the intensity of 16 prespecified emotions during the
      preceding 5 minutes. Measurements of QT interval and interbeat intervals were
      synchronized with emotion ratings. RESULTS: Low Arousal Positive Affect was
      associated with significant increases in QT interval corrected for heart rate
      (using Fridericia's QTc) (p < .001), whereas higher arousal Activated Positive
      Affect (p < .001) and Activated Negative Affect (p < .01) were associated with
      significant decreases in QTc. Changes in QTc as a function of daily emotion
      ranged from 5-ms increases to 11-ms decreases. High-frequency heart rate
      variability (vagal tone) was positively correlated with QTc (p < .001). The
      effects of each positive emotion variable on QTc were greater in LQT2 than LQT1
      patients (p < .001). CONCLUSION: Ventricular repolarization duration (QTc)
      changes dynamically as a function of daily emotion. These changes are relatively
      small and do not constitute a risk in themselves. In the context of other risk
      factors, however, they may contribute to ventricular arrhythmias in vulnerable
      populations.

PMID- 21183718
TI  - Transcription termination maintains chromosome integrity.
AB  - DNA replication fork movement is impeded by collisions with transcription
      elongation complexes (TEC). We propose that a critical function of transcription
      termination factors is to prevent TEC from blocking DNA replication and inducing
      replication fork arrest, one consequence of which is DNA double-strand breaks. We
      show that inhibition of Rho-dependent transcription termination by bicyclomycin
      in Escherichia coli induced double-strand breaks. Cells deleted for Rho-cofactors
      nusA and nusG were hypersensitive to bicyclomycin, and had extensive chromosome
      fragmentation even in the absence of the drug. An RNA polymerase mutation that
      destabilizes TEC (rpoB*35) increased bicyclomycin resistance >40-fold. Double
      strand break formation depended on DNA replication, and can be explained by
      replication fork collapse. Deleting recombination genes required for replication
      fork repair (recB and ruvC) increased sensitivity to bicyclomycin, as did loss of
      the replication fork reloading helicases rep and priA. We propose that Rho
      responds to a translocating replisome by releasing obstructing TEC.

PMID- 21183719
TI  - Statistical method for revealing form-function relations in biological networks.
AB  - Over the past decade, a number of researchers in systems biology have sought to
      relate the function of biological systems to their network-level descriptions-
      lists of the most important players and the pairwise interactions between them.
      Both for large networks (in which statistical analysis is often framed in terms
      of the abundance of repeated small subgraphs) and for small networks which can be
      analyzed in greater detail (or even synthesized in vivo and subjected to
      experiment), revealing the relationship between the topology of small subgraphs
      and their biological function has been a central goal. We here seek to pose this
      revelation as a statistical task, illustrated using a particular setup which has
      been constructed experimentally and for which parameterized models of
      transcriptional regulation have been studied extensively. The question "how does
      function follow form" is here mathematized by identifying which topological
      attributes correlate with the diverse possible information-processing tasks which
      a transcriptional regulatory network can realize. The resulting method reveals
      one form-function relationship which had earlier been predicted based on analytic
      results, and reveals a second for which we can provide an analytic
      interpretation. Resulting source code is distributed via
      http://formfunction.sourceforge.net.

PMID- 21183720
TI  - N-terminal domain of human Hsp90 triggers binding to the cochaperone p23.
AB  - The molecular chaperone Hsp90 is a protein folding machine that is conserved from
      bacteria to man. Human, cytosolic Hsp90 is dedicated to folding of chiefly signal
      transduction components. The chaperoning mechanism of Hsp90 is controlled by ATP
      and various cochaperones, but is poorly understood and controversial. Here, we
      characterized the Apo and ATP states of the 170-kDa human Hsp90 full-length
      protein by NMR spectroscopy in solution, and we elucidated the mechanism of the
      inhibition of its ATPase by its cochaperone p23. We assigned isoleucine side
      chains of Hsp90 via specific isotope labeling of their delta-methyl groups, which
      allowed the NMR analysis of the full-length protein. We found that ATP caused
      exclusively local changes in Hsp90's N-terminal nucleotide-binding domain. Native
      mass spectrometry showed that Hsp90 and p23 form a 22 complex via a positively
      cooperative mechanism. Despite this stoichiometry, NMR data indicated that the
      complex was not fully symmetric. The p23-dependent NMR shifts mapped to both the
      lid and the adenine end of Hsp90's ATP binding pocket, but also to large parts of
      the middle domain. Shifts distant from the p23 binding site reflect p23-induced
      conformational changes in Hsp90. Together, we conclude that it is Hsp90's
      nucleotide-binding domain that triggers the formation of the Hsp90(2)p23(2)
      complex. We anticipate that our NMR approach has significant impact on future
      studies of full-length Hsp90 with cofactors and substrates, but also for the
      development of Hsp90 inhibiting anticancer drugs.

PMID- 21183722
TI  - Autoimmune limbic encephalitis as an emerging pediatric condition: case report
      and review of the literature.
AB  - Limbic encephalitis, first described in the 1960s as a paraneoplastic condition,
      has emerged as an autoimmune condition, occurring often without evidence of an
      underlying tumor. Many novel autoantibodies have been identified, and this
      diagnosis is increasingly being made in the pediatric population. This article
      reports the case of a 16-year-old boy who presented following gastrointestinal
      illness with subacute evolution of neuropsychiatric symptoms. Brain magnetic
      resonance imaging revealed progressive hippocampal signal abnormality and
      swelling. N-methyl-D-aspartate (NMDA) receptor antibody was detected in serum.
      The patient responded well to pharmacological immunotherapy but has residual
      cognitive deficits. The available literature on this condition is reviewed.
      Limbic encephalitis should be considered in the differential diagnosis in
      children presenting with encephalopathy, particularly with neuropsychiatric
      manifestations. Long-term surveillance and close follow-up are required to
      accurately clarify tumor risk and natural history of this condition in children
      and balance these factors with risks of radiation exposure through imaging.

PMID- 21183721
TI  - Disease allele-dependent small-molecule sensitivities in blood cells from
      monogenic diabetes.
AB  - Even as genetic studies identify alleles that influence human disease
      susceptibility, it remains challenging to understand their functional
      significance and how they contribute to disease phenotypes. Here, we describe an
      approach to translate discoveries from human genetics into functional and
      therapeutic hypotheses by relating human genetic variation to small-molecule
      sensitivities. We use small-molecule probes modulating a breadth of targets and
      processes to reveal disease allele-dependent sensitivities, using cells from
      multiple individuals with an extreme form of diabetes (maturity onset diabetes of
      the young type 1, caused by mutation in the orphan nuclear receptor HNF4alpha).
      This approach enabled the discovery of small molecules that show mechanistically
      revealing and therapeutically relevant interactions with HNF4alpha in both
      lymphoblasts and pancreatic beta-cells, including compounds that physically
      interact with HNF4alpha. Compounds including US Food and Drug Administration
      approved drugs were identified that favorably modulate a critical disease
      phenotype, insulin secretion from beta-cells. This method may suggest therapeutic
      hypotheses for other nonblood disorders.

PMID- 21183723
TI  - Does one more medication help? Effect of adding another anticonvulsant in
      childhood epilepsy.
AB  - OBJECTIVES: To study adding an anticonvulsant in children with uncontrolled
      epilepsy on >= 1 appropriate anticonvulsants. METHODS: Chart review, patients
      with intractable epilepsy in a neurology clinic July 1, 2004 to December 31,
      2007. Inclusion: Children on >= 1 stable anticonvulsant who had a second, third,
      or fourth anticonvulsant added. EXCLUSIONS: Noncompliance, subtherapeutic doses,
      and/or serum anticonvulsant levels, inappropriate anticonvulsant for seizure
      type, inadequate documentation, infantile spasms, or significant dosage changes
      in the baseline anticonvulsant(s) over the follow-up period. Patients were
      followed until further therapeutic changes occurred or September 30, 2008,
      whichever came first. OUTCOME: >= 50% decrease in seizure frequency. RESULTS:
      Charts reviewed: 1886. Patients who met criteria: 84. Time to assessment: 4 weeks
      to 42 months (median = 7 months). >= 50% reduction in seizure frequency: 35 of 52
      patients with second agent added; 5 of 30 patients with third agent added (P =
      .0001). CONCLUSIONS: Worthwhile seizure reduction is reasonably likely with the
      addition of a second anticonvulsant, but much less likely with the addition of
      third anticonvulsant.

PMID- 21183724
TI  - Efficacy and safety of rituximab in pediatric neuromyelitis optica.
AB  - Neuromyelitis optica is a central nervous system disease characterized by optic
      neuritis and transverse myelitis. It is a devastating illness, and early
      treatment may prevent future relapses and severe disability. However, there is
      much variability in protocols used for treatment. In limited studies, rituximab
      has shown efficacy in adult neuromyelitis optica patients. There is a paucity of
      literature on the efficacy and tolerability of rituximab in the pediatric
      population. The authors report the use of rituximab in 2 pediatric patients with
      neuromyelitis optica, demonstrating its efficacy, dosing, and tolerability. This
      report may be a useful guide for administering rituximab safely in pediatric
      neuromyelitis optica patients.

PMID- 21183725
TI  - Early ''relapse'' after herpetic encephalitis: extensive white matter lesions in
      an infant with interferon production deficit.
AB  - Acute secondary neurological deterioration after herpes simplex encephalitis has
      been reported. An immune-mediated process is thought to be responsible for some
      cases. The authors report the case of an infant who presented with fever,
      irritability, and orofacial involuntary movements, 15 days after herpes
      encephalitis onset. Polymerase chain reaction for herpes simplex virus was
      negative, and the magnetic resonance imaging revealed extensive white matter
      lesions. Chorea appeared only 11 days later. Raised immunoglobulin G index with
      oligoclonal bands and spreading of white matter lesions corroborated an immune
      mediated etiology. An interferon production deficit was also detected. This case
      alerts that this form of ''relapse'' appears earlier than previously reported. A
      high level of suspicion is needed in the presence of atypical neurological
      deterioration and early white matter lesions should be considered as a warning
      sign. This case is also relevant because it associates, for the first time, an
      immune-mediated ''relapse'' to an interferon production deficit.

PMID- 21183726
TI  - Fall risk factors in community-dwelling elderly who receive Medicaid-supported
      home- and community-based care services.
AB  - OBJECTIVE: This study identifies fall risk factors in an understudied population
      of older people who receive community-based care services. METHOD: Data were
      collected from enrollees of Ohio's Medicaid home- and community-based waiver
      program (preadmission screening system providing options and resources today
      [PASSPORT]). A total of 23,182 participants receiving PASSPORT services in
      2005/2006 was classified as fallers and nonfallers, and a variety of risk factors
      for falling was analyzed using logistic regressions. RESULTS: The following
      factors were identified as risk factors for falling: previous fall history, older
      age, White race, incontinence, higher number of medications, fewer numbers of
      activity of daily living limitations, unsteady gait, tremor, grasping strength,
      and absence of supervision. DISCUSSION: Identifying risk factors for the
      participants of a Medicaid home- and community-based waiver program are useful
      for a fall risk assessment, but it would be most helpful if the community-based
      care service programs incorporate measurements of known fall risk factors into
      their regular data collection, if not already included.

PMID- 21183727
TI  - Failure of the adipocytokine, resistin, to protect the heart from ischemia
      reperfusion injury.
AB  - Experimental studies have linked the adipocytokines with acute cardioprotection.
      Whether the adipocytokine, resistin, confers protection is, however, debatable.
      In the current study, the actions of resistin, administered at reperfusion, were
      investigated in in vivo and in vitro rodent and in vitro human models of
      myocardial ischemia-reperfusion (I/R) injury. Resistin did not reduce infarct
      size in Langendorff-perfused rat hearts or murine hearts perfused in vivo.
      Resistin also did not protect human atrial muscle subjected to hypoxia
      reoxygenation. Although cyclosporin A delayed mitochondrial permeability
      transition pore (MPTP) opening in murine cardiomyocytes, resistin was
      ineffective. Western blot analysis revealed that resistin treatment was
      associated with enhanced phosphorylation of Akt, at both the serine-473 (+ 51.9%,
      P = .01) and threonine-308 (+107%, P < .01) phosphorylation sites, although not
      to the extent seen with ischemic preconditioning (+132.5%, P = .002 and +389.1%,
      P < .01, respectively). We conclude that resistin administered at reperfusion at
      concentrations/doses equivalent to normal (upper end) and pathological serum
      levels does not protect against I/R injury or inhibit MPTP opening.

PMID- 21183729
TI  - Mechanism of sarpogrelate action in improving cardiac function in diabetes.
AB  - Although sarpogrelate, a 5-HT(2A) receptor antagonist, has been reported to exert
      beneficial effects in diabetes, the mechanisms of its action are not understood.
      In this study, diabetes was induced in rats by an injection of streptozotocin (65
      mg/kg) and the animals were assessed 7 weeks later. Decreased serum insulin as
      well as increased serum glucose, cholesterol, and triglyceride levels in diabetic
      animals were associated with increased blood pressure and heart/body weight
      ratio. Impaired cardiac performance in diabetic animals was evident by decreased
      heart rate, left ventricular developed pressure, rate of pressure development,
      and rate of pressure decay. Treatment of diabetic animals with sarpogrelate (5
      mg/kg) or insulin (10 units/kg) daily for 6 weeks attenuated the observed changes
      in serum insulin, glucose, and lipid levels as well as blood pressure and cardiac
      function by varying degrees. Protein content for membrane glucose transporters
      (GLUT-1 and GLUT-4) was depressed in diabetic heart; the observed alteration in
      GLUT-4 was partially prevented by both sarpogrelate and insulin, whereas that in
      GLUT-1 was attenuated by sarpogrelate only. Incubation of myoblast cells with
      sarpogrelate and insulin stimulated glucose uptake; these effects were additive.
      5-hydroxytryptamine was found to inhibit glucose-induced insulin release from the
      pancreas; this effect was prevented by sarpogrelate. These results suggest that
      sarpogrelate may improve cardiac function in chronic diabetes by promoting the
      expression of membrane glucose transporters as well as by releasing insulin from
      the pancreas.

PMID- 21183730
TI  - Is the standard weight-based dosing of dobutamine for stress testing appropriate
      for patients of widely varying body mass index?
AB  - BACKGROUND: Although a gradual increase in heart rate (HR) during dobutamine
      stress testing (DST) is desired, few data exists regarding whether this is
      similarly achieved in patients of widely varying body mass index (BMI). Whether
      difference in BMI contributes to variation in the hemodynamic and symptomatic
      response to dobutamine is also unknown. METHODS: From prospectively acquired data
      of 2776 consecutive patients who underwent DST according to standard weight-based
      clinical protocol, we classified patients into 4 groups of BMI (kg/m( 2)): <25
      (normal), 25 to 29.9 (overweight), 30 to 39.9 (obese), and >= 40 (severely obese)
      and compared the rate of increase of HR, mean blood pressure, and development of
      symptoms for the groups. RESULTS: Age was 68 + 12 years, 52% were men, BMI was
      29.8 + 6.6 kg/m(2) (range 14.5-81.4), 198 (7%) had BMI >= 40, and target HR was
      achieved in 2433 (88%). The rate of increase in HR was similar for each group of
      BMI after adjustment for age, gender, baseline HR, negative chronotropic use, and
      atropine administration. The percentage of patients in each group who achieved
      target HR was similar and the percentage of target HR achieved at each stage of
      dobutamine was essentially equivalent. Blood pressure responses and development
      of symptoms were similar in the 4 groups of BMI. Independent predictors of
      failure to achieve target HR included age, diabetes mellitus, treatment with
      negative chronotropic medications, and baseline HR; BMI was not a predictor (odds
      ratio [OR] 0.98, P = .086). CONCLUSION: The current weight-based protocol of
      dobutamine dosing for DST results in similar increases in HR and blood pressure
      for patients of widely varying BMI.

PMID- 21183728
TI  - Therapeutic potential for protein kinase C inhibitor in vascular restenosis.
AB  - Vascular restenosis, an overreaction of biological response to injury, is
      initialized by thrombosis and inflammation. This response is characterized by
      increased smooth muscle cell migration and proliferation. Available
      pharmacological treatments include anticoagulants, antiplatelet agents,
      immunosuppressants, and antiproliferation agents. Protein kinase C (PKC), a large
      family of serine/threonine kinases, has been shown to participate in various
      pathological stages of restenosis. Consequently, PKC inhibitors are expected to
      exert a wide range of pharmacological activities therapeutically beneficial for
      restenosis. In this review, the roles of PKC isozymes in platelets, leukocytes,
      endothelial cells, and smooth muscle cells are discussed, with emphasis given to
      smooth muscle cells. We will describe cellular and animal studies assessing
      prevention of restenosis with PKC inhibitors, particularly targeting -alpha, 
      beta, -delta, and -zeta isozymes. The delivery strategy, efficacy, and safety of
      such PKC regulators will also be discussed.

PMID- 21183731
TI  - Transcriptional activation of apolipoprotein CIII expression by glucose may
      contribute to diabetic dyslipidemia.
AB  - OBJECTIVE: Hypertriglyceridemia and fatty liver are common in patients with type
      2 diabetes, but the factors connecting alterations in glucose metabolism with
      plasma and liver lipid metabolism remain unclear. Apolipoprotein CIII (apoCIII),
      a regulator of hepatic and plasma triglyceride metabolism, is elevated in type 2
      diabetes. In this study, we analyzed whether apoCIII is affected by altered
      glucose metabolism. METHODS AND RESULTS: Liver-specific insulin receptor
      deficient mice display lower hepatic apoCIII mRNA levels than controls,
      suggesting that factors other than insulin regulate apoCIII in vivo. Glucose
      induces apoCIII transcription in primary rat hepatocytes and immortalized human
      hepatocytes via a mechanism involving the transcription factors carbohydrate
      response element-binding protein and hepatocyte nuclear factor-4alpha. ApoCIII
      induction by glucose is blunted by treatment with agonists of farnesoid X
      receptor and peroxisome proliferator-activated receptor-alpha but not liver X
      receptor, ie, nuclear receptors controlling triglyceride metabolism. Moreover, in
      obese humans, plasma apoCIII protein correlates more closely with plasma fasting
      glucose and glucose excursion after oral glucose load than with insulin.
      CONCLUSIONS: Glucose induces apoCIII transcription, which may represent a
      mechanism linking hyperglycemia, hypertriglyceridemia, and cardiovascular disease
      in type 2 diabetes.

PMID- 21183732
TI  - Phase I/IIa clinical trial of therapeutic angiogenesis using hepatocyte growth
      factor gene transfer to treat critical limb ischemia.
AB  - OBJECTIVE: To evaluate the safety and feasibility of intramuscular gene transfer
      using naked plasmid DNA-encoding hepatocyte growth factor (HGF) and to assess its
      potential therapeutic benefit in patients with critical limb ischemia. METHODS
      AND RESULTS: Gene transfer was performed in 22 patients with critical limb
      ischemia by intramuscular injection of HGF plasmid, either 2 or 4 mg, 2 times.
      Safety, ankle-brachial index, resting pain on a 10-cm visual analog scale, wound
      healing, and walking distance were evaluated before treatment and at 2 months
      after injection. No serious adverse event caused by gene transfer was detected
      over a follow-up of 6 months. Of particular importance, no peripheral edema, in
      contrast to that seen after treatment with vascular endothelial growth factor,
      was observed. In addition, the systemic HGF protein level did not increase during
      the study. At 2 months after gene transfer, the mean +/- SD ankle-brachial index
      increased from 0.46 +/- 0.08 to 0.59 +/- 0.13 (P<0.001), the mean +/- SD size of
      the largest ischemic ulcers decreased from 3.08 +/- 1.54 to 2.32 +/- 1.88 cm
      (P=0.007), and the mean +/- SD visual analog scale score decreased from 5.92 +/-
      1.67 to 3.04 +/- 2.50 cm (P=0.001). An increase in ankle-brachial index by >0.1,
      a reduction in ulcer size by >25%, and a reduction in visual analog scale score
      by >2 cm at 2 months after gene transfer were observed in 11 (64.7%) of 17 limbs,
      18 (72%) of 25 ulcers, and 8 (61.5%) of 13 limbs, respectively. CONCLUSIONS:
      Intramuscular injection of naked HGF plasmid is safe and feasible and can achieve
      successful improvement of ischemic limbs as sole therapy.

PMID- 21183733
TI  - Systemic markers of interferon-gamma-mediated immune activation and long-term
      prognosis in patients with stable coronary artery disease.
AB  - OBJECTIVE: Interferon gamma (IFN-gamma) is centrally involved in atherosclerosis
      related inflammation, but its activity cannot be reliably assessed by systemic
      measurements. In activated macrophages, IFN-gamma stimulates production of
      neopterin and conversion of tryptophan to kynurenine. We evaluated the
      relationships of plasma neopterin and plasma kynurenine:tryptophan ratio (KTR) to
      long-term prognosis in patients with stable angina pectoris and angiographically
      verified significant coronary artery disease. METHODS AND RESULTS: Samples were
      obtained from 2380 patients with a mean age of 63.7 years; 77.3% were men. During
      a median follow-up of 56 months, 10.8% of patients experienced a major coronary
      event (MCE), and 9.5% died. For MCE, each SD increment of neopterin and KTR
      (logarithmically transformed) was associated with multivariable adjusted hazard
      ratios and 95% CIs of 1.28 (1.10 to 1.48) and 1.28 (1.12 to 1.48), respectively.
      The corresponding hazard ratios (95% CIs) for all-cause mortality were 1.40 (1.21
      to 1.62) (neopterin) and 1.23 (1.06 to 1.43) (KTR). CONCLUSIONS: In patients with
      stable angina pectoris, systemic markers of IFN-gamma activity, plasma neopterin,
      and plasma KTR provide similar risk estimates for MCE and mortality. Our results
      support experimental data linking IFN-gamma to acute atherosclerotic
      complications.

PMID- 21183734
TI  - A modified sesamol derivative inhibits progression of atherosclerosis.
AB  - OBJECTIVE: Sesamol, a phenolic component of lignans, has been previously shown to
      reduce lipopolysaccharide-induced oxidative stress and upregulate
      phosphatidylinositol 3-kinase/Akt/endothelial nitric oxide synthase pathways. In
      the present study, we synthesized a modified form of sesamol (INV-403) to enhance
      its properties and assessed its effects on atherosclerosis. METHODS AND RESULTS:
      Watanabe heritable hyperlipidemic rabbits were fed with high-cholesterol chow for
      6 weeks and then randomized to receive high-cholesterol diet either alone or
      combined with INV-403 (20 mg/kg per day) for 12 weeks. Serial MRI analysis
      demonstrated that INV-403 rapidly reduced atherosclerotic plaques (within 6
      weeks), with confirmatory morphological analysis at 12 weeks posttreatment
      revealing reduced atherosclerosis paralleled by reduction in lipid and
      inflammatory cell content. Consistent with its effect on atherosclerosis, INV-403
      improved vascular function (decreased constriction to angiotensin II and
      increased relaxation to acetylcholine), reduced systemic and plaque oxidative
      stress, and inhibited nuclear factor-kappaB activation via effects on nuclear
      factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
      (IkappaBalpha) phosphorylation with coordinate reduction in key endothelial
      adhesion molecules. In vitro experiments in cultured endothelial cells revealed
      effects of INV-403 in reducing IkappaBalpha phosphorylation via inhibition of
      IkappaB kinase 2 (IKK2). CONCLUSIONS: INV-403 is a novel modified lignan
      derivative that potently inhibits atherosclerosis progression via its effects on
      IKK2 and nuclear factor-kappaB signaling.

PMID- 21183735
TI  - Platelet-endothelial cell adhesion molecule-1 regulates endothelial NO synthase
      activity and localization through signal transducers and activators of
      transcription 3-dependent NOSTRIN expression.
AB  - BACKGROUND: NO produced by the endothelial NO synthase (eNOS) is an important
      regulator of cardiovascular physiological and pathological features. eNOS is
      activated by numerous stimuli, and its activity is tightly regulated. Platelet
      endothelial cell adhesion molecule-1 (PECAM-1) has been implicated in regulating
      eNOS activity in response to shear stress. The current study was conducted to
      determine the role of PECAM-1 in the regulation of basal eNOS activity. METHODS
      AND RESULTS: We demonstrate that PECAM-1-knockout ECs have increased basal eNOS
      activity and NO production. Mechanistically, increased eNOS activity is
      associated with a decrease in the inhibitory interaction of eNOS with caveolin-1,
      impaired subcellular localization of eNOS, and decreased eNOS traffic inducer
      (NOSTRIN) expression in the absence of PECAM-1. Furthermore, we demonstrate that
      activation of blunted signal transducers and activators of transcription 3
      (STAT3) in the absence of PECAM-1 results in decreased NOSTRIN expression via
      direct binding of the signal transducers and activators of transcription 3 to the
      NOSTRIN promoter. CONCLUSIONS: Our results reveal an elegant mechanism of eNOS
      regulation by PECAM-1 through signal transducers and activators of transcription
      3-mediated transcriptional control of NOSTRIN.

PMID- 21183736
TI  - Serum hepcidin and macrophage iron correlate with MCP-1 release and vascular
      damage in patients with metabolic syndrome alterations.
AB  - OBJECTIVE: Increased body iron stores and hepcidin have been hypothesized to
      promote atherosclerosis by inducing macrophage iron accumulation and release of
      cytokines, but direct demonstration in human cells is lacking. The aim of this
      study was to evaluate the effect of iron on cytokine release in monocytes ex vivo
      and the correlation with vascular damage and to evaluate the relationship among
      serum levels of hepcidin, cytokines, and vascular damage in patients with
      metabolic syndrome alterations. METHODS AND RESULTS: Manipulation of iron status
      with ferric ammonium citrate and hepcidin-25 induced monocyte chemoattractant
      protein (MCP)-1 and interleukin-6 in human differentiating monocytes of patients
      with hyperferritinemia associated with the metabolic syndrome (n=11), but not in
      subjects with hemochromatosis or HFE mutations impairing iron accumulation
      (n=15), and the degree of induction correlated with the presence of carotid
      plaques, detected by echocolor-Doppler. In monocytes of healthy subjects (n=7),
      iron and hepcidin increased the mRNA levels and release of MCP-1, but not of
      interleukin-6. In 130 patients with metabolic alterations, MCP-1 levels, as
      detected by ELISA, were correlated with hepcidin-25 measured by time-of-flight
      mass spectrometry (P=0.005) and were an independent predictor of the presence of
      carotid plaques (P=0.05). CONCLUSIONS: Hepcidin and macrophage iron correlate
      with MCP-1 release and vascular damage in high-risk individuals with metabolic
      alterations.

PMID- 21183737
TI  - Therapeutic potential of poly(ADP-ribose) polymerase inhibitor AG014699 in human
      cancers with mutated or methylated BRCA1 or BRCA2.
AB  - BACKGROUND: Mutations in BRCA1 and BRCA2 (BRCA1/2), components of the homologous
      recombination DNA repair (HRR) pathway, are associated with hereditary breast and
      ovarian cancers. Poly(ADP-ribose) polymerase (PARP) inhibitors are selectively
      cytotoxic to animal cells with defective HRR, but results in human cancer cells
      have been contradictory. We undertook, to our knowledge, the first comprehensive
      in vitro and in vivo investigations of the antitumor activity of the PARP
      inhibitor AG014699 in human cancer cells carrying mutated or epigenetically
      silenced BRCA1/2. METHODS: We used nine human cell lines, four with nonmutated
      BRCA1/2 (MCF7, MDA-MB-231, and HCC1937-BRCA1 [breast cancer] and OSEC-2 [ovarian
      surface epithelial]), two with mutated BRCA1 (MDA-MB-436 and HCC1937 [breast
      cancer]), one with mutated BRCA2 (CAPAN-1 [pancreatic cancer]), one that was
      heterozygous for BRCA2 (OSEC-1 [ovarian surface epithelial]), and one with
      epigenetically silenced BRCA1 (UACC3199 [breast cancer]), and two Chinese hamster
      ovary cell lines, parental AA8 and XRCC3 mutated IRS 1SF. We assessed
      cytotoxicity, DNA damage, and HRR function. Antitumor activity of AG014699 was
      determined by growth of xenograft tumors (five mice per treatment group). Long
      term safety of AG014699 was assessed. RESULTS: AG014699 (<=10 MUM) was cytotoxic
      to cells with mutated BRCA1/2 or XRCC3 and to UACC3199 cells with epigenetically
      silenced BRCA1 but not to cells without BRCA1/2 or XRCC3 mutations or that were
      heterozygous for BRCA2 mutation. AG014699 induced DNA double-strand breaks in all
      nine cell lines studied. HRR was observed only in cells with functional BRCA1/2
      proteins. Growth of xenograft tumors with BRCA1/2 mutations or with
      epigenetically silenced BRCA1 was reduced by AG014699 treatment, and combination
      treatment with AG014699 plus carboplatin was more effective than either drug
      alone. AG014699 was not toxic in mice with nonmutated or heterozygous BRCA2.
      CONCLUSION: Human cancer cells or xenograft tumors with mutated or epigenetically
      silenced BRCA1/2 were sensitive to AG014699 monotherapy, indicating a potential
      role for PARP inhibitors in sporadic human cancers.

PMID- 21183738
TI  - Circulating platelet-activating factor is primarily cleared by transport, not
      intravascular hydrolysis by lipoprotein-associated phospholipase A2/ PAF
      acetylhydrolase.
AB  - RATIONALE: The phospholipid platelet-activating factor (PAF) stimulates all cells
      of the innate immune system and numerous cardiovascular cells. A single enzyme
      (plasma PAF acetylhydrolase [PAF-AH] or lipoprotein-associated phospholipase [Lp
      PL]A(2)) in plasma hydrolyzes PAF, but significant controversy exists whether its
      action is pro- or antiinflammatory and accordingly whether its inhibition will
      slow cardiovascular disease. OBJECTIVE: We sought to define how PAF and related
      short-chain oxidized phospholipids turnover in vivo and the role of PAF
      acetylhydrolase/Lp-PLA(2) in this process. METHODS AND RESULTS: [(3)H-acetyl]PAF
      was hydrolyzed by murine or human plasma (t(1/2), 3 and 7 minutes, respectively),
      but injected [(3)H-acetyl]PAF disappeared from murine circulation more quickly
      (t(1/2), <30 seconds). [(3)H]PAF clearance was unchanged in PAF receptor(-/-)
      animals, or over the first 2 half-lives in PAF-AH(-/-) animals. [(3)H]PAF
      turnover was reduced by coinjecting excess unlabeled PAF or an oxidatively
      truncated phospholipid, and [(3)H]PAF clearance was slowed in hyperlipidemic
      apolipoprotein (apo)E(-/-) mice with excess circulating oxidatively truncated
      phospholipids. [(3)H]PAF, fluorescent NBD-PAF, or fluorescent oxidatively
      truncated phospholipid were primarily accumulated by liver and lung, and were
      transported into endothelium as intact phospholipids through a common mechanism
      involving TMEM30a. CONCLUSIONS: Circulating PAF and oxidized phospholipids are
      continually and rapidly cleared, and hence continually and rapidly produced.
      Saturable PAF receptor-independent transport, rather than just intravascular
      hydrolysis, controls circulating inflammatory and proapoptotic oxidized
      phospholipid mediators. Intravascular PAF has access to intracellular
      compartments. Inflammatory and proapoptotic phospholipids may accumulate in the
      circulation as transport is overwhelmed by substrates in hyperlipidemia.

PMID- 21183739
TI  - Vasoconstrictor potential of coronary aspirate from patients undergoing stenting
      of saphenous vein aortocoronary bypass grafts and its pharmacological
      attenuation.
AB  - RATIONALE: Stent implantation into atherosclerotic plaques releases, apart from
      particulate debris, soluble substances that contribute to impaired microvascular
      perfusion. OBJECTIVE: To quantify the release of vasoconstrictors and to
      determine the efficacy of coronary dilators to attenuate their action. METHODS
      AND RESULTS: Using a distal protection/aspiration device, coronary arterial blood
      was retrieved before and during stenting in 22 patients with severe saphenous
      vein aorto-coronary bypass stenoses. The release of catecholamines, endothelin,
      serotonin, thromboxane B(2), and tumor necrosis factor (TNF)alpha was measured.
      The response of rat mesenteric arteries with intact (+E) and denuded (-E)
      endothelium to aspirate plasma was normalized to that by KCl. Responses to
      selective receptor blockade, adenosine, nitroprusside, and verapamil against the
      aspirate-induced constriction were determined. The coronary arterial plasma
      withdrawn before stenting induced 21+/-5% and the aspirate plasma after stenting
      induced 95+/-8% of maximum KCl-induced vasoconstriction. Serotonin, thromboxane
      B(2), and TNFalpha release into aspirate plasma increased by 1.9+/-0.2 MUmol/L,
      25.6+/-3.1 pg/mL, and 19.7+/-6.1 pg/mL, respectively, during stenting. The
      aspirate-induced vasoconstriction was largely antagonized by selective serotonin
      receptor blockade, with little further antagonism by additional thromboxane
      receptor blockade. TNFalpha did not induce constriction per se but potentiated
      the constriction with serotonin and the thromboxane-analog U-46619 in arteries
      +E. The concentrations to induce half-maximal vasodilation were comparable for
      nitroprusside (+E, 3.3*10(-8); -E, 1.9*10(-8) mol/L) and verapamil (+E, 8.3*10(
      8); -E, 7.8*10(-8) mol/L), and the vasoconstriction was eventually eliminated.
      The vasodilator response to adenosine was dependent on functional endothelium and
      weaker. CONCLUSION: Serotonin is the main coronary vasoconstrictor after
      stenting, and thromboxane and TNFalpha somewhat potentiate the serotonin
      response. Nitroprusside and verapamil are more potent than adenosine to attenuate
      the aspirate plasma-induced vasoconstriction, and they are not dependent on
      functional endothelium.

PMID- 21183740
TI  - Thioredoxin 1 negatively regulates angiotensin II-induced cardiac hypertrophy
      through upregulation of miR-98/let-7.
AB  - RATIONALE: Thioredoxin (Trx)1 inhibits pathological cardiac hypertrophy.
      MicroRNAs (miRNAs) are small noncoding RNAs that downregulate posttranscriptional
      expression of target molecules. OBJECTIVES: We investigated the role of miRNAs in
      mediating the antihypertrophic effect of Trx1 on angiotensin II (Ang II)-induced
      cardiac hypertrophy. METHODS AND RESULTS: Microarray analyses of mature rodent
      microRNAs and quantitative RT-PCR/Northern blot analyses showed that Trx1
      upregulates members of the let-7 family, including miR-98, in the heart and the
      cardiomyocytes therein. Adenovirus-mediated expression of miR-98 in
      cardiomyocytes reduced cell size both at baseline and in response to Ang II.
      Knockdown of miR-98, and of other members of the let-7 family, augmented Ang II
      induced cardiac hypertrophy, and attenuated Trx1-mediated inhibition of Ang II
      induced cardiac hypertrophy, suggesting that endogenous miR-98/let-7 mediates the
      antihypertrophic effect of Trx1. Cyclin D2 is one of the predicted targets of miR
      98. Ang II significantly upregulated cyclin D2, which in turn plays an essential
      role in mediating Ang II-induced cardiac hypertrophy, whereas overexpression of
      Trx1 inhibited Ang II-induced upregulation of cyclin D2. miR-98 decreased both
      expression of cyclin D2 and the activity of a cyclin D2 3'UTR luciferase
      reporter, suggesting that both Trx1 and miR-98 negatively regulate cyclin D2.
      Overexpression of cyclin D2 attenuated the suppression of Ang II-induced cardiac
      hypertrophy by miR-98, suggesting that the antihypertrophic actions of miR-98 are
      mediated in part by downregulation of cyclin D2. CONCLUSIONS: These results
      suggest that Trx1 upregulates expression of the let-7 family, including miR-98,
      which in turn inhibits cardiac hypertrophy, in part through downregulation of
      cyclin D2.

PMID- 21183741
TI  - Reciprocal control of hERG stability by Hsp70 and Hsc70 with implication for
      restoration of LQT2 mutant stability.
AB  - RATIONALE: The human ether-a-go-go-related gene (hERG) encodes the alpha subunit
      of the potassium current I(Kr). It is highly expressed in cardiomyocytes and its
      mutations cause long QT syndrome type 2. Heat shock protein (Hsp)70 is known to
      promote maturation of hERG. Hsp70 and heat shock cognate (Hsc70) 70 has been
      suggested to play a similar function. However, Hsc70 has recently been reported
      to counteract Hsp70. OBJECTIVE: We investigated whether Hsc70 counteracts Hsp70
      in the control of wild-type and mutant hERG stability. METHODS AND RESULTS:
      Coexpression of Hsp70 with hERG in HEK293 cells suppressed hERG ubiquitination
      and increased the levels of both immature and mature forms of hERG.
      Immunocytochemistry revealed increased levels of hERG in the endoplasmic
      reticulum and on the cell surface. Electrophysiological studies showed increased
      I(Kr). All these effects of Hsp70 were abolished by Hsc70 coexpression. Heat
      shock treatment of HL-1 mouse cardiomyocytes induced endogenous Hsp70, switched
      mouse ERG associated with Hsc70 to Hsp70, increased I(Kr), and shortened action
      potential duration. Channels with disease-causing missense mutations in
      intracellular domains had a higher binding capacity to Hsc70 than wild-type
      channels and channels with mutations in the pore region. Knockdown of Hsc70 by
      small interfering RNA or heat shock prevented degradation of mutant hERG proteins
      with mutations in intracellular domains. CONCLUSIONS: These results indicate
      reciprocal control of hERG stability by Hsp70 and Hsc70. Hsc70 is a potential
      target in the treatment of LQT2 resulting from missense hERG mutations.

PMID- 21183742
TI  - Increased risk of stroke in the year after a hip fracture: a population-based
      follow-up study.
AB  - BACKGROUND AND PURPOSE: Stroke is a documented risk factor for hip fracture.
      However, no documented studies are available on the risk of stroke among patients
      with hip fracture. This study investigated the frequency and risk of stroke after
      hip fracture using a nationwide population-based study. METHODS: The study cohort
      included 2101 patients hospitalized with a principal diagnosis of hip fracture
      from 2001 to 2004. The comparison cohort consisted of 6303 randomly selected
      subjects matched on sex, age, and year of index healthcare use as controls. We
      tracked patients for a 1-year period from their index healthcare encounter to
      identify those who had a stroke. Stratified Cox proportional hazard regression
      was performed to evaluate the association of hip fracture with subsequent stroke
      during 1-year follow-up. RESULTS: Of a total of 8404 patients, 86 (4.1%) from the
      study group and 170 (2.7%) from the comparison group had strokes during the
      follow-up period (P<0.001). The stratified Cox proportional analysis shows that
      the 1-year crude hazard of stroke among patients with hip fracture was 1.55 times
      (95% CI, 1.19 to 2.03; P=0.001) that of the comparison group. Furthermore, after
      adjusting for the major cardiovascular risk factors, the increased stroke risk of
      patients with hip fracture persisted at about the same level as in the unadjusted
      analysis (hazard ratio, 1.53; 95% CI, 1.17 to 2.01; P=0.002). CONCLUSIONS: Hip
      fracture is associated with increased risk of stroke in the next year.

PMID- 21183743
TI  - Recurrent stroke due to a novel voltage sensor mutation in Cav2.1 responds to
      verapamil.
AB  - BACKGROUND AND PURPOSE: Familial hemiplegic migraine is characterized by
      recurrent migraine, hemiparesis, and ataxia. Causes may be mutations in calcium
      and sodium channels or in a subunit of the Na/K-ATPse. Migraine treatment with
      calcium channel blockers was only successful in some patients. Summary of Case-
      We describe a 6-year-old girl with recurrent ischemic strokes after minor head
      trauma associated with seizures, hemiparesis, fever, and altered consciousness.
      Genetic analysis revealed a spontaneous, novel dominant CACNA1A mutation (c.4046G
      >A, p.R1349Q) that removed a highly conserved arginine of the voltage sensing
      region of the P/Q-type Ca(v)2.1 channel. Because a homologous mutation in the
      tottering-5J mouse increased open probability of the channel as well as calcium
      influx, we treated the patient with the calcium channel blocker verapamil during
      characteristic prodromi after head trauma. Treatment was instantly effective and
      prevented a new stroke. CONCLUSIONS: CACNA1A mutations should be considered in
      the diagnostic workup of childhood stroke, especially if associated with ataxia
      and migraine.

PMID- 21183744
TI  - Remote limb ischemic postconditioning protects against neonatal hypoxic-ischemic
      brain injury in rat pups by the opioid receptor/Akt pathway.
AB  - BACKGROUND AND PURPOSE: Remote ischemic postconditoning, a phenomenon in which
      brief ischemic stimuli of 1 organ protect another organ against an ischemic
      insult, has been demonstrated to protect the myocardium and adult brain in animal
      models. However, mediators of the protection and underlying mechanisms remain to
      be elucidated. In the present study, we tested the hypothesis that remote limb
      ischemic postconditioning applied immediately after hypoxia provides
      neuroprotection in a rat model of neonatal hypoxia-ischemia (HI) by mechanisms
      involving activation of the opioid receptor/phosphatidylinositol-3-kinase/Akt
      signaling pathway. METHODS: HI was induced in postnatal Day 10 rat pups by
      unilateral carotid ligation and 2 hours of hypoxia. Limb ischemic
      postconditioning was induced by 4 conditioning cycles of 10 minutes of ischemia
      and reperfusion on both hind limbs immediately after HI. The opioid antagonist
      naloxone, phosphatidylinositol-3-kinase inhibitor wortmannin, or opioid agonist
      morphine was administered to determine underlying mechanisms. Infarct volume,
      brain atrophy, and neurological outcomes after HI were evaluated. Expression of
      phosphorylated Akt, Bax, and phosphorylated ERK1/2 was determined by Western
      blotting. RESULTS: Limb ischemic postconditioning significantly reduced infarct
      volume at 48 hours and improved functional outcomes at 4 weeks after HI. Naloxone
      and wortmannin abrogated the postconditioning-mediated infarct-limiting effect.
      Morphine given immediately after hypoxia also decreased infarct volume.
      Furthermore, limb ischemic postconditioning recovered Akt activity and decreased
      Bax expression, whereas no differences in phosphorylated ERK1/2expression were
      observed. CONCLUSIONS: Limb ischemic postconditioning protects against neonatal
      HI brain injury in rats by activating the opioid receptor/phosphatidylinositol-3
      kinase/Akt signaling pathway.

PMID- 21183745
TI  - Association between carotid artery plaque ulceration and plaque composition
      evaluated with multidetector CT angiography.
AB  - BACKGROUND AND PURPOSE: Symptomatic carotid artery plaque ulceration is
      associated with distinct plaque components such as a large lipid-rich necrotic
      core (LR-NC) in ischemic stroke patients with a >=50% carotid stenosis. We
      evaluated the associations between carotid artery plaque ulceration and plaque
      characteristics in ischemic stroke patients with >=50% stenosis, as well as in
      those with a low degree of stenosis (0% to 49%). METHODS: Consecutive patients
      (n=346) with symptoms in the anterior circulation were evaluated with
      multidetector CT angiography (MDCTA) for the presence of atherosclerotic plaque,
      degree of stenosis, and plaque ulceration in the symptomatic carotid artery.
      Plaque volume and plaque component proportions of LR-NC, fibrous tissue, and
      calcification were measured. The associations between plaque ulceration and
      plaque characteristics were analyzed using logistic regression. RESULTS:
      Atherosclerotic plaque was present in 185 patients. Plaque ulcerations were
      present in 38 (21%) patients, of which half had a low degree stenosis (0% to
      49%). Plaque volume was significantly larger in ulcerated plaques. After
      adjustment for age, sex, and degree of stenosis, LR-NC proportion was strongly
      associated with plaque ulceration (odds ratio, 2.21; 95% CI, 1.49 to 3.27),
      whereas calcification proportion was inversely associated with plaque ulceration
      (odds ratio, 0.60; 95% CI, 0.40 to 0.89). These associations remained significant
      in patients with a low degree stenosis (0% to 49%). CONCLUSIONS: Plaque volume,
      degree of stenosis, and LR-NC proportion evaluated noninvasively with MDCTA are
      associated with carotid artery plaque ulceration, even in patients with a low
      degree stenosis (0% to 49%). Plaque volume and composition analysis with MDCTA
      may identify rupture prone plaques and improve risk stratification in ischemic
      stroke patients.

PMID- 21183746
TI  - Pharmacogenetic effect of the stromelysin (MMP3) polymorphism on stroke risk in
      relation to antihypertensive treatment: the genetics of hypertension associated
      treatment study.
AB  - BACKGROUND AND PURPOSE: Atherothrombotic diseases including stroke share a common
      etiology of atherosclerosis, and susceptibility to atherosclerosis has a genetic
      component. Stromelysin-1 (matrix metalloproteinase-3 [MMP3]) regulates arterial
      matrix composition and is a candidate gene for atherothrombosis. A common
      polymorphism of MMP3 alters expression levels and affects atherosclerotic
      progression and plaque stability. As part of the Genetics of Hypertension
      Associated Treatment study, ancillary to the Antihypertensive and Lipid Lowering
      to Prevent Heart Attack Trial, we evaluated the 5A/6A polymorphism in MMP3 to
      determine its association with stroke and determine whether it modifies clinical
      outcome response to blood pressure-lowering drugs. METHODS: The effect of the
      MMP3 5A/6A polymorphism on stroke rates was examined by using multivariate
      adjusted Cox regression models, including a test for interactions between
      genotype and antihypertensive drug class. RESULTS: Compared with participants
      treated with chlorthalidone with the 6A/6A genotype, individuals with the 6A/6A
      genotype randomized to lisinopril had higher stroke rates (hazard ratio=1.32; 95%
      CI, 1.08 to 1.61; P=0.007) and 5A/6A individuals taking lisinopril had lower
      stroke rates (hazard ratio(interaction)=0.74; 95% CI, 0.53 to 1.04;
      P(interaction)=0.08), whereas 5A/5A individuals taking lisinopril had the lowest
      stroke rate (hazard ratio(interaction)=0.51; 95% CI, 0.31 to 0.85;
      P(interaction)=0.009). There were no pharmacogenetic differences in stroke rate
      by genotype in patients taking amlodipine or doxazosin vs chlorthalidone.
      CONCLUSIONS: The MMP3 6A/6A genotype is associated with an increased risk of
      stroke in hypertensive subjects taking lisinopril compared with patients treated
      with chlorthalidone, whereas a protective effect was found for 5A/5A individuals
      treated with lisinopril. Genetic screening for the MMP3 5A/6A genotype might be a
      useful tool to select optimal antihypertensive therapy if this finding is
      replicated. Clinical Trial Registration- URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00563901.

PMID- 21183747
TI  - Relationship between baseline blood pressure parameters (including mean pressure,
      pulse pressure, and variability) and early outcome after stroke: data from the
      Tinzaparin in Acute Ischaemic Stroke Trial (TAIST).
AB  - BACKGROUND AND PURPOSE: High blood pressure (BP) in acute stroke is associated
      independently with a poor outcome. Recent evidence suggests that other
      hemodynamic parameters may also be associated with outcomes following stroke.
      METHODS: The relationship between baseline BP, heart rate, and other hemodynamic
      parameters, and early outcomes were assessed using data from TAIST trial.
      RESULTS: Death or neurological deterioration at day 10 was associated, both in
      unadjusted and adjusted analyses, with systolic BP (adjusted OR, 1.02; 95% CI,
      1.01-1.03), mean arterial pressure (OR, 1.02; 95% CI, 1.01-1.04), pulse pressure
      (OR, 1.02; 95% CI, 1.01-1.03), and BP variability (OR, 1.03; 95% CI, 1.01-1.05).
      Similar relationships were noted for deterioration alone, and recurrent stroke.
      CONCLUSIONS: Early death or neurologic deterioration, deterioration, and
      recurrent stroke are associated independently with high systolic BP, mean
      arterial pressure, pulse pressure, and BP variability. These measures offer
      potential therapeutic targets for improving early outcome after acute ischemic
      stroke.

PMID- 21183748
TI  - Diagnostic accuracy of the Barthel Index for measuring activities of daily living
      outcome after ischemic hemispheric stroke: does early poststroke timing of
      assessment matter?
AB  - BACKGROUND AND PURPOSE: This study investigated the diagnostic accuracy of the
      Barthel Index (BI) in 206 stroke patients, measured within 72 hours, for
      activities of daily living at 6 months and determined whether the timing of BI
      assessment during the first days affects the accuracy of predicting activities of
      daily living outcome at 6 months. METHODS: Receiver operating characteristic
      curves were constructed to determine the area under the curve and optimal cutoff
      points for BI at Days 2, 5, and 9. OR, sensitivity, specificity, positive
      predictive value, and negative predictive value were calculated to predict BI
      >=19. RESULTS: The area under the curve ranged from 0.785 on Day 2 to 0.837 and
      0.848 on Days 5 and 9. Comparison of the receiver operating characteristic curves
      showed that the area under the curve was significantly different between Days 2
      and 5 (P<0.001) and between Days 2 and 9 (P<0.001). No significant difference was
      found between Days 5 and 9 (P=0.08). Using a BI cutoff score of 7, the positive
      predictive value gradually increased from 0.696 on Day 2 to 0.817 on Day 2 to
      0.864 on Day 9, whereas negative predictive value declined from 0.778 on Day 2 to
      0.613 on Day 9. CONCLUSIONS: Assessment of the BI early poststroke showed good
      discriminative properties for final outcome of BI at 6 months. However, Day 5
      proved to be the earliest time for making an optimal prediction of final outcome
      of activities of daily living. The BI should be measured at the end of the first
      week in hospital-based stroke units for early rehabilitation management.

PMID- 21183749
TI  - Discriminating carotid atherosclerotic lesion severity by luminal stenosis and
      plaque burden: a comparison utilizing high-resolution magnetic resonance imaging
      at 3.0 Tesla.
AB  - BACKGROUND AND PURPOSE: To determine associations between stenosis, measures of
      plaque burden, and compositional features of carotid atherosclerosis, including
      high-risk features of intraplaque hemorrhage (IPH) and surface disruption.
      METHODS: Institutional Review Board approval and informed consent for all
      participants were obtained before study initiation. Patients with either carotid
      stenosis >50% by duplex ultrasound or suspected coronary artery disease underwent
      multi-contrast carotid MRI at 3.0 T. For each artery, stenosis, percent wall
      volume (PWV=100%*wall volume/total vessel volume), and mean wall thickness (MWT)
      were measured. Presence or absence of a lipid-rich necrotic core, calcification,
      IPH, and surface disruption were recorded. RESULTS: One hundred eighty-one
      patients were included in the final analysis. The area under the curve (AUC)
      calculated from receiver-operating-characteristics analysis found the presence of
      IPH was similarly classified by stenosis (AUC=0.82), PWV (AUC=0.88), and MWT
      (AUC=0.88). Notably, IPH was present in the lowest category of each parameter.
      Prevalence of IPH in arteries with 0% stenosis was 4.4%. In arteries with PWV
      <40%, prevalence was 3.2%; in arteries with MWT <1.0 mm, prevalence was 2.3%.
      Strength of classification for surface disruption was similarly classified by
      stenosis (AUC=0.87), PWV (AUC=0.93), and MWT (AUC=0.94). CONCLUSIONS: Measures of
      plaque burden do not substantially improve disease assessment compared to
      stenosis. The finding of IPH in all categories of stenosis and plaque burden
      suggests that direct characterization of plaque composition and surface status is
      necessary to fully discriminate disease severity.

PMID- 21183751
TI  - Activation of epsilon protein kinase C-mediated anti-apoptosis is involved in
      rapid tolerance induced by electroacupuncture pretreatment through cannabinoid
      receptor type 1.
AB  - BACKGROUND AND PURPOSE: Our previous study has demonstrated that the rapid
      tolerance to cerebral ischemia by electroacupuncture (EA) pretreatment was
      possibly mediated through an endocannabinoid system-related mechanism. The
      purpose of this study was to investigate whether activation of epsilon protein
      kinase C (epsilonPKC) was involved in EA pretreatment-induced neuroprotection via
      cannabinoid receptor type 1 in a rat model of transient focal cerebral ischemia.
      METHODS: The activation of epsilonPKC in the ipsilateral brain tissues after EA
      pretreatment was investigated in the presence or absence of cannabinoid receptor
      antagonists. At 2 hours after the end of EA pretreatment, focal cerebral ischemia
      was induced by middle cerebral artery occlusion for 120 minutes in rats. The
      neurobehavioral scores, infarction volumes, neuronal apoptosis, and the
      expression of Bcl-2 and Bax were evaluated after reperfusion in the presence or
      absence of epsilonPKC-selective peptide inhibitor (TAT-epsilonV1-2) or activator
      (TAT-psiepsilonRACK). RESULTS: EA pretreatment enhanced epsilonPKC activation.
      Systemic delivery of TAT-psiepsilonRACK conferred neuroprotection against a
      subsequent cerebral ischemic event when delivered 2 hours before ischemia.
      Pretreatment with EA reduced infarct volumes, improved neurological outcome,
      inhibited neuronal apoptosis, and increased the Bcl-2-to-Bax ratio after
      reperfusion, and the beneficial effects were attenuated by TAT-epsilonV1-2. In
      addition, the blockade of cannabinoid receptor type 1, but not cannabinoid
      receptor type 2 receptor, reversed the increase in epsilonPKC activation and
      neuroprotection induced by EA pretreatment. CONCLUSIONS: EA pretreatment may
      activate endogenous epsilonPKC-mediated anti-apoptosis to protect against
      ischemic damage after focal cerebral ischemia via cannabinoid receptor type 1,
      which represents a new mechanism of EA pretreatment-induced rapid tolerance to
      focal cerebral ischemia in rats.

PMID- 21183752
TI  - Determinants of quality of life after stroke in China: the ChinaQUEST (QUality
      Evaluation of Stroke care and Treatment) study.
AB  - BACKGROUND AND PURPOSE: Limited information exists on the long-term consequences
      of stroke in China. We aimed to describe the profile and determinants of health
      related quality of life among 12-month survivors of stroke. METHODS: The
      ChinaQUEST (QUality Evaluation of Stroke care and Treatment) study was a
      prospective 62-hospital registry study of patients with acute stroke (ischemic
      stroke and intracerebral hemorrhage). Health-related quality of life was
      determined in 12-month survivors using a 35-item quality-of-life questionnaire
      (QOL-35) designed specifically for use in Chinese people. Proxy responses were
      used in those who were unable to personally complete the QOL-35. RESULTS: A total
      of 4283 12-month stroke survivors completed assessments directly (1730 [40.4%])
      or by a proxy (2553 [59.6%]). Mean (SD) health-related quality of life scores
      were higher in self-responders (70 [0.3] out of a best possible 100 score) than
      in proxy responders (60 [0.3]; P<0.001). The strongest baseline variables that
      predicted "low" (below median) health-related quality of life scores in self
      responders were having a lower income (income <10 000 Chinese Yuan Renminbi [CNY,
      approximately US $1428] versus >19 000 CNY [approximately US $2714]; OR, 2.06;
      95% CI, 1.37 to 3.10) and being disabled at discharge (OR, 3.65; 95% CI, 2.72 to
      4.91). Proxy responders had similar predictive factors, including being disabled
      at discharge (OR, 4.99; 95% CI, 4.00 to 6.21), but income was not significant.
      CONCLUSIONS: In China, the strongest predictor of 12-month health-related quality
      of life after stroke is level of disability at hospital discharge. Level of
      income was another important factor. Health insurance schemes that offset the
      economic impact of stroke could help improve the health and well-being of Chinese
      people affected by stroke.

PMID- 21183753
TI  - Decreased kidney function: an unrecognized and often untreated risk factor for
      secondary cardiovascular events after carotid surgery.
AB  - BACKGROUND AND PURPOSE: Chronic kidney disease is an important risk factor for
      development and progression of atherosclerosis. The objective of the current
      study was to investigate the contribution of moderate kidney failure to
      cardiovascular (CV) mortality and morbidity after carotid endarterectomy (CEA).
      In addition, we investigated which proportion received optimal medical treatment
      or underwent diagnostic workup of the kidneys prior to CEA. METHODS: Between 2002
      and 2009, 1085 patients undergoing CEA were included in this study. Estimated
      glomerular filtration rate (eGFR) was assessed at baseline. Moderate kidney
      failure was defined as an eGFR 30-59 and compared with normal or mildly reduced
      kidney function (eGFR >=60). Primary endpoint was CV death, composed of fatal
      myocardial infarction, fatal stroke, and ruptured abdominal aneurysm. Secondary
      endpoints were CV morbidity. RESULTS: Moderate kidney failure (eGFR 30-59) was
      observed in 26.5% (288/1085) of the patients. During a median follow-up of 2.95
      years (0.0 to 3.0 years), the adjusted hazard ratio for CV death with an eGFR 30
      59 was 2.22 (1.27 to 3.89). Adjusted hazard ratio for MI with an eGFR 30-59 was
      1.90 (1.04 to 3.47). No higher risk for stroke and peripheral interventions was
      observed. Of all patients with an eGFR 30-59, 38.3% (105/274) received
      angiotensin-converting enzyme inhibitors, 74.5% (204/274) received statins, and
      34.4% (99/288) visited a nephrologist. CONCLUSIONS: Patients with an eGFR 30-59
      have a 2.2-fold increased risk for CV death and 1.9-fold increased risk for
      myocardial infarction the 3 three years after CEA compared with patients with an
      eGFR >=60, independent of other CV risk factors. A minority of these patients
      receive optimal medical treatment, which might explain the increased risk for
      progression of chronic kidney disease and CV morbidity and mortality.

PMID- 21183755
TI  - Papers from the 2009 Eisenberg Conference: Translating information into action:
      improving quality of care through interactive media.

PMID- 21183754
TI  - Estimation and validation of a multiattribute model of Alzheimer disease
      progression.
AB  - OBJECTIVES: To estimate and validate a multiattribute model of the clinical
      course of Alzheimer disease (AD) from mild AD to death in a high-quality
      prospective cohort study, and to estimate the impact of hypothetical
      modifications to AD progression rates on costs associated with Medicare and
      Medicaid services. DATA AND METHODS: The authors estimated sex-specific
      longitudinal Grade of Membership (GoM) models for AD patients (103 men, 149
      women) in the initial cohort of the Predictors Study (1989-2001) based on 80
      individual measures obtained every 6 mo for 10 y. These models were replicated
      for AD patients (106 men, 148 women) in the 2nd Predictors Study cohort (1997
      2007). Model validation required that the disease-specific transition parameters
      be identical for both Predictors Study cohorts. Medicare costs were estimated
      from the National Long Term Care Survey. RESULTS: Sex-specific models were
      validated using the 2nd Predictors Study cohort with the GoM transition
      parameters constrained to the values estimated for the 1st Predictors Study
      cohort; 57 to 61 of the 80 individual measures contributed significantly to the
      GoM models. Simulated, cost-free interventions in the rate of progression of AD
      indicated that large potential cost offsets could occur for patients at the
      earliest stages of AD. CONCLUSIONS: AD progression is characterized by a small
      number of parameters governing changes in large numbers of correlated indicators
      of AD severity. The analysis confirmed that the progression of AD represents a
      complex multidimensional physiological process that is similar across different
      study cohorts. The estimates suggested that there could be large cost offsets to
      Medicare and Medicaid from the slowing of AD progression among patients with mild
      AD. The methodology appears generally applicable in AD modeling.

PMID- 21183756
TI  - Revisiting decision aids: about definitions and classifications.

PMID- 21183750
TI  - Anatomical and technical factors associated with stroke or death during carotid
      angioplasty and stenting: results from the endarterectomy versus angioplasty in
      patients with symptomatic severe carotid stenosis (EVA-3S) trial and systematic
      review.
AB  - BACKGROUND AND PURPOSE: The purposes of this study were to assess the
      relationships between anatomic and technical factors and the 30-day risk of
      stroke or death after carotid angioplasty and stenting in the Endarterectomy
      versus Stenting in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S)
      trial and to perform a systematic review of the literature. METHODS: We included
      patients from EVA-3S in whom carotid stenting was attempted irrespective of
      allocated treatment. Two radiologists blinded to clinical data independently
      assessed the aortic arch and carotid arteries on procedural angiograms. In
      addition, we performed a systematic review of studies that reported 30-day risk
      of stroke or death in relation with arterial anatomy and technique. Outcomes were
      stroke or death and stroke occurring within 30 days of the carotid angioplasty
      and stenting procedure. RESULTS: Two hundred sixty-two patients from EVA-3S
      fulfilled the inclusion criteria (including 1 initially allocated to surgery and
      13 in whom stent insertion failed).Within 30 days after the procedure, 25 (9.5%)
      patients had a stroke or had died. The risk of stroke or death was higher in
      patients with internal carotid artery-common carotid artery angulation >=60
      degrees  (relative risk, 4.96; 2.29 to 10.74) and lower in those treated with
      cerebral protection devices (relative risk [RR], 0.38; 0.17 to 0.85). In the
      systematic review (56 studies; 34 398 patients), the risk of stroke or death was
      higher in patients with left-sided carotid angioplasty and stenting (RR, 1.29;
      1.05 to 1.58), increased internal carotid artery-common carotid artery angulation
      (RR, 3.41; 1.52 to 7.63), and when the target internal carotid artery stenosis
      was >10 mm (RR, 2.36; 1.28 to 3.38). There was no significant increase in risk of
      stroke or death in patients with Type III aortic arch, aortic arch calcification,
      or with ostial involvement, calcification, ulceration or degree of stenosis of
      the target internal carotid artery stenosis. The use of a cerebral protection
      device was associated with a lower risk of stroke or death (RR, 0.55; 0.41 to
      0.73). Risk was not related with stent or cerebral protection device type.
      CONCLUSIONS: Our results strongly suggest that some technical and anatomic
      factors, especially extreme angulation of the carotid artery, have an impact on
      the risks of carotid angioplasty and stenting.

PMID- 21183757
TI  - Decision aids: evolving from novelties to effective communication tools.

PMID- 21183758
TI  - AHRQ White Paper: Use of clinical decision rules for point-of-care decision
      support.
AB  - Translation of research into clinical practice remains a barrier, with
      inconsistent adoption of effective treatments and useful tests. Clinical decision
      rules (CDRs) integrate information from several clinical or laboratory findings
      to provide quantitative estimates of risk for a diagnosis or clinical outcome.
      They are increasingly reported in the literature and have the potential to
      provide a bridge that helps translate findings from original research studies
      into clinical practice. Unlike formal aids for shared decision making, they are
      pragmatic solutions that provide discrete quantitative data to aid clinicians and
      patients in decision making. These quantitative data can help inform the informal
      episodes of shared decision making that frequently take place at the point of
      care. Methods used to develop CDRs include expert opinion, multivariate models,
      point scores, and classification and regression trees Desirable CDRs are valid
      (make accurate predictions of risk), relevant (have been shown to improve patient
      oriented outcomes), are easy to use at the point of care, are acceptable (with
      good face validity and transparency of recommendations), and are situated in the
      clinical context. The latter means that the rule places patients in risk groups
      that are clinically useful (i.e., below the test threshold or above the treatment
      threshold) and does so in adequate numbers to make use of the CDR a worthwhile
      investment in time. CDRs meeting these criteria should be integrated with
      electronic health records, populating the point score or decision tree with
      individual patient data and performing calculations automatically to streamline
      decision making.

PMID- 21183759
TI  - Electronic health records to coordinate decision making for complex patients:
      what can we learn from wiki?
AB  - BACKGROUND: Processes of communication that guide decision making among
      clinicians collaboratively caring for complex patients are poorly understood and
      vary based on local contexts. In this paper, the authors characterize these
      processes and propose a wiki-style communication model to improve coordination of
      decision making among clinicians using an integrated electronic health record
      (EHR). METHODS: A narrative review of current patterns of communication among
      clinicians sharing medical decisions focusing on the emerging and potential roles
      of EHRs to enhance communication among clinicians caring for complex patients.
      RESULTS: . The authors present the taxonomy of decision making and communication
      among clinicians caring for complex patients. They then adapt wiki-style
      communication to propose a novel model of communication among clinicians for
      decision making within multidisciplinary disease management programs. Future
      innovations using wiki-style communication among clinicians are also described
      and placed in the context of medical decisions by clinicians working together in
      disease management programs. CONCLUSIONS: EHR-based wiki-style applications may
      have the potential to improve communication and care coordination among
      clinicians caring for complex patients. This could lead to improved quality and
      safety within multidisciplinary disease management programs.

PMID- 21183760
TI  - Interactive media for diabetes self-management: issues in maximizing public
      health impact.
AB  - BACKGROUND: Diabetes self-management presents a series of challenging tasks, and
      primary care, where the majority of cases of adult diabetes are treated, is hard
      pressed to address these issues given competing demands. This article discusses
      how interactive media (IM) can be used to support diabetes self-management.
      METHODS: Following a brief review of the literature, the 5 As framework for
      enhancing the effectiveness of health behavior counseling and the RE-AIM model
      for estimating and enhancing public health impact are used to frame discussion of
      the strengths and limitations of IM for diabetes shared decision making and self
      management support. RESULTS: Data and lessons learned from a series of randomized
      trials of IM for diabetes self-management education are summarized around 2 key
      issues. The first is enhancing patient engagement in decision making and includes
      enhancing user experience and engagement, improving quality of care, and
      promoting collaborative action planning and follow-up. The second is getting such
      resources into place and sustaining them in real-world primary care settings and
      involves enhancing participation at patient, clinician, and health care system
      levels and enhancing the generalizability of results. CONCLUSIONS: . Key
      opportunities for IM to support diabetes self-management include assessment of
      information for shared decision making, assistance with problem-solving self
      management challenges, and provision of follow-up support. A key current
      challenge is the linkage of IM supports to the rest of the patient's care, and
      collection of cost-effectiveness data is a key need for future research.

PMID- 21183761
TI  - Expression, purification, crystallization, and preliminary X-ray diffraction
      analysis of the human TLE1 Q domain.
AB  - Human transducin-like enhancer of split 1 (TLE1) plays crucial roles in a number
      of developmental processes and is involved in pathogenesis of malignancy tumors.
      The N-terminal glutamine-rich domain (Q domain) of TLE1 mediates its
      tetramerization and interactions with different DNA-binding transcription factors
      to regulate Notch and Wnt signaling pathways. To better understand the molecular
      mechanism of TLE1's functions in these pathways, we cloned, purified, and
      crystallized the TLE1 Q domain (TLE1-Q). The crystals belong to space group
      C222(1), with the complete diffraction data of the native and Se-Met TLE1-Q
      collected to 3.5 and 4.1 A resolutions, respectively. The phasing-solving and
      model building are in progress.

PMID- 21183762
TI  - Use of low-molecular-weight heparins during percutaneous coronary intervention.
AB  - Patients with acute coronary syndromes (ACS) may transition to percutaneous
      coronary intervention (PCI) after an initial phase of medical management that
      includes anticoagulation. When patients come to the catheterization laboratory,
      it is important to consider previously received anticoagulation. Enoxaparin has
      emerged as a more effective, yet simple, agent for use in the emergency room or
      upon initial encounter of the ACS patient. However, there may be uncertainty
      among physicians on the adequacy and way to use anticoagulation in the transition
      to the catheterization laboratory. Recently, new data have emerged on the use of
      enoxaparin in the catheterization laboratory. Dosing schedules based on
      pharmacodynamic and clinical data offer a seamless transition for enoxaparin from
      the medical management phase to PCI. In this paper, the pharmacokinetics of
      enoxaparin are reviewed and recommendations for anticoagulant regimens provided
      based upon the timing of presentation and pre-catheterization dosing.

PMID- 21183763
TI  - A randomized pilot trial for aggressive therapeutic approaches in aspirin
      resistant patients undergoing percutaneous coronary intervention.
AB  - BACKGROUND: There is great variability among individual patients in platelet
      inhibition after aspirin intake. Aspirin resistance has been associated with a
      higher incidence of ischemic events after percutaneous coronary intervention
      (PCI). The optimal antiplatelet therapy in aspirin-resistant patients undergoing
      PCI is unknown. The objective of this study was to evaluate whether aggressive
      antiplatelet therapy would reduce ischemic events in aspirin-resistant patients
      after PCI. METHODS: A total of 330 patients undergoing PCI (with bivalirudin)
      were screened for aspirin responsiveness. The resulting 36 aspirin-resistant
      patients were randomized into two arms: 1) conventional strategy patients
      received 325 mg aspirin orally and a loading dose of 600 mg clopidogrel at the
      time of the procedure; and 2) aggressive strategy patients received similar
      amounts of aspirin and clopidogrel, with the addition of an intravenous
      glycoprotein IIb/IIIa inhibitor bolus intraprocedurally. The primary outcome was
      an elevation of cardiac enzymes within 24 hours post procedure. The secondary
      outcome was a composite of major adverse cardiac events including death,
      myocardial infarction, stent thrombosis and urgent revascularization, and
      bleeding up to 30 days. RESULTS: Primary outcome occurred in 22% of the
      conventional strategy group and 11% of the aggressive strategy group (p = 0.36).
      The secondary outcome was reached in 27.8% of the conventional group and 5.5% of
      the aggressive strategy group (p = 0.17), which is suggestive of a statistical
      trend toward more ischemic events with conventional therapy. Importantly, there
      were 2 cases of definite stent thrombosis in the conventional strategy group.
      CONCLUSION: In aspirin-resistant patients, aggressive antiplatelet therapy tended
      to show better outcomes after PCI, without an increase in bleeding. These
      findings need validation in a large, randomized study.

PMID- 21183764
TI  - Platelet resistance - much known and much more unknown.

PMID- 21183765
TI  - Baseline C-reactive protein serum levels and in-stent restenosis pattern after m
      TOR inhibitors drug-eluting stent implantation.
AB  - BACKGROUND: A diffuse pattern of in-stent restenosis (ISR) has been shown to have
      a worse prognosis when compared to a focal pattern. It is still unknown whether
      baseline C-reactive protein (CRP) levels predict ISR pattern. METHODS: Our
      database was searched retrospectively for patients presenting with ISR after m
      TOR inhibitor drug-eluting stent (DES) implantation from January 2007 to December
      2009. Angiographic restenosis patterns were evaluated according to the simplified
      Mehran classification and patients were allocated either to the diffuse or focal
      pattern group. Predictors of restenosis pattern were assessed among clinical,
      angiographic, procedural and laboratory data, including baseline high-sensitivity
      CRP, recorded at the time of the first percutaneous intervention. RESULTS: 72
      patients (age, 65 +/- 9 years; male sex, 64%) found to have ISR after DES
      implantation were enrolled. 34 patients presented with a focal pattern, whereas
      38 patients presented with a diffuse pattern. At multivariate analysis, CRP
      levels were the only independent predictor of a diffuse ISR pattern [odds ratio,
      2.5; 95% confidence interval, 1.4-4.3; p = 0.001)]. Rising CRP tertiles were
      associated with an increased rate of diffuse pattern (13% versus 26% versus 61%;
      p for trend = 0.0001). CONCLUSION: Baseline CRP serum levels are associated with
      a diffuse ISR pattern after m-TOR inhibitor DES implantation. These findings
      suggest that baseline inflammatory reactivity may contribute to aggressive
      restenosis occurring despite drug elution.

PMID- 21183766
TI  - Impact of abciximab in diabetic patients with acute coronary syndrome who undergo
      percutaneous coronary intervention: results from a high-volume, single-center
      registry.
AB  - BACKGROUND: The prevalence of diabetes mellitus (DM) and ischemic heart disease
      is increasing. Moreover, patients with DM experiencing an acute coronary syndrome
      (ACS) have an increased risk of adverse outcomes after revascularization compared
      to non-diabetics. Data have suggested that the glycoprotein IIb/IIIa inhibitor
      abciximab might be more efficient in diabetics than in those without DM. METHODS
      AND RESULTS: We evaluated the effect of abciximab in patients with DM and ACS
      from our percutaneous coronary intervention (PCI) registry. Among 5,003 patients
      with ACS who underwent PCI, 629 had DM. Patients were followed for up to 3 years
      with regard to mortality, myocardial infarction (MI) and target vessel
      revascularization (TVR). Despite a more severe risk profile, adjusted analyses
      revealed a marked reduction in TVR (hazard ratio [HR], 0.30; confidence interval
      [CI], 0.14-0.63; p = 0.002), mortality (HR, 0.53; CI, 0.28-0.97; p = 0.04) and
      the combined endpoint, also including MI (HR, 0.53; CI, 0.35-0.79; p = 0.002) in
      the DM patients who received abciximab compared to those who did not, resulting
      in a risk of reaching the endpoints at levels similar to the risk in patients
      without DM. The reduction in MI was not significant. CONCLUSION: Our findings
      suggest that abciximab administered to ACS patients with DM during PCI reduces
      mortality and the need for TVR to rates similar to those seen in patients without
      DM and far below the risk in DM patients who do not receive abciximab.

PMID- 21183767
TI  - Drug-eluting stents following rotational atherectomy for heavily calcified
      coronary lesions: long-term clinical outcomes.
AB  - BACKGROUND: Rotational atherectomy followed by drug-eluting stent (DES)
      implantation for complex, severely calcified lesions is a rational combination
      that has not been sufficiently evaluated. METHODS: We investigated 102
      consecutive patients with angiographic evidence of heavily calcified lesions that
      underwent DES implantation following rotational atherectomy at our institution
      between June 2005 and October 2009, and we examined the long-term clinical
      outcomes. The major adverse cardiac events monitored were death, myocardial
      infarction and target lesion revascularization. RESULTS: Patients were 68.8 +/-
      7.4 years old, 52.9% were diabetic, and 12.7% had chronic kidney disease. Forty
      seven patients (46.1%) had three-vessel disease, and 13 (12.7%) had left main
      coronary artery stenosis. The radial approach was used in 37.3% of cases. The
      procedure was successful in 97%. In-hospital death occurred in 1 patient (0.9%),
      and 3 patients (2.9%) developed stent thrombosis. At the mean follow-up period of
      15 months (range 1- 54), the total cardiac death rate was 4.9%, target lesion
      revascularization was 8.8% and the incidence of myocardial infarction was 3.9%.
      The combined endpoint occurred in 12.7% of cases. CONCLUSION: DES following
      rotational atherectomy for heavily calcified coronary lesions is a safe and
      effective procedure that provides good long-term clinical outcomes.

PMID- 21183768
TI  - Rotational atherectomy in the DES era - away go troubles down the drain?

PMID- 21183769
TI  - Novel use of the Heartrail catheter as a thrombectomy device.
AB  - The presence of thrombus is independently associated with adverse outcomes during
      percutaneous coronary intervention (PCI), particularly in those cases involving a
      large thrombus burden such as in saphenous vein grafts (SVGs) or during primary
      PCI. Mechanical thrombectomy devices are used to reduce the thrombus burden in
      such high-risk procedures to reduce the risk of distal embolization and slow flow
      and no-reflow. Here we describe 3 cases of successful use of a stent delivery
      system with a wide-bore lumen, the "five-in-six" Heartrail catheter, as a
      thrombectomy device in SVG lesions and primary PCI following failure of
      conventional simple aspiration thrombectomy catheters.

PMID- 21183770
TI  - Left ventricular malposition of an ICD lead in a patient with Ebstein's anomaly.

PMID- 21183771
TI  - Prosthetic aortic valve abscess producing left main coronary artery occlusion in
      a patient with type IV dual left anterior descending coronary artery.
AB  - A 22-year-old female with a history of aortic and mitral valve replacement was
      admitted with a 4-week history of dyspnea and chest pain. Emergency coronary
      angiography revealed not only external compression of the left main coronary
      artery due to an aortic root abscess, but also the dual left anterior descending
      artery arising from the left and right coronary sinus. Although aortic root
      abscess is a well recognized complication of aortic valve endocarditis, coronary
      artery compression is an unusual mode of presentation. The binary distribution of
      the left anterior descending artery may limit the extent of ischemic insult to
      the anterior wall and thus led to a more insidious clinical course.

PMID- 21183772
TI  -  Novel use of a local drug delivery catheter for coronary perforation.
AB  - Coronary perforation is a complication of percutaneous coronary intervention
      that may be fatal. Conventionally, a perfusion balloon catheter is used for
      treatment, but may not always be available. We report a case in which bleeding
      due to coronary perforation was successfully treated without induction of
      ischemia using a local drug delivery catheter as a perfusion device.

PMID- 21183773
TI  - Anomalous origin of all three coronary arteries from right sinus of Valsalva in
      a patient with angina pectoris.
AB  - Anomalous origin of coronary arteries is uncommon, and all 3 coronary arteries
      arising from a single sinus of Valsalva is very rare. The anomaly has been
      associated with myocardial infarction and sudden cardiac death in particular when
      the anomalous left coronary artery courses between the great vessels. Imaging
      modalities have a complementary role to angiography in the diagnosis.
      Percutaneous interventions are technically difficult. Surgical options like
      direct repair of anomalous artery or coronary artery bypass graft can be helpful.
      We report a case of a patient who presented with chest pain and was found to have
      all 3 coronary arteries arising from the right sinus of Valsalva.

PMID- 21183774
TI  - Thrombectomy and fibrinolytic therapy of prosthetic valve thrombosis complicated
      by coronary embolism.
AB  - Prosthetic valve thrombosis is rare; its complication by coronary embolism is
      even more uncommon and when present, often fatal. Here, we present a rare case of
      mechanical aortic valve thrombosis with coronary emboli presenting in cardiogenic
      shock, managed successfully using a hybrid approach of mechanical thrombectomy
      and intravenous fibrinolytic therapy. 

PMID- 21183775
TI  - Patent ductus arteriosus associated with aberrant right subclavian artery: two
      cases, one successful interventional closure of PDA .
AB  - Two children were sent to the catheterization laboratory for transcatheter
      closure of patent ductus arteriosus (PDA). During the intervention, cineangiogram
      revealed associated aberrant right subclavian artery (ARSA). Both patients had
      left-sided aortic arch. The first patient was sent to surgery after one
      unsuccessful attempt to close the PDA due to the proximity of the ARSA and also
      because of other concomitant cardiac lesions. We successfully treated the second
      patient by closing the PDA with a Nit-Occlud(r) PDA occlusion device (Pfm
      Medical, Carlsbad, California). Similar mirror cases of PDA closure with aberrant
      left subclavian artery and right aortic arch have been reported. Anatomic
      features, as well as the technique and management of the procedure, are discussed
      here.

PMID- 21183776
TI  - Closure of aortic paravalvular leak under intravascular ultrasound and
      intracardiac echocardiography guidance.
AB  - Aortic paravalvular leaks after aortic valve replacement surgery - though not
      uncommon as an incidental finding - may become clinically significant in up to 5%
      of patients. Open surgical correction by either direct suturing or patching of
      the defect or reoperative valve replacement is associated with significant
      morbidity and mortality. Relatively few case reports are available in the
      literature addressing percutaneous closure of aortic paravalvular leaks. We
      describe the novel use of intracardiac echocardiography and intravascular
      ultrasound to guide closure strategy selection and subsequent deployment of an
      Amplatzer duct occluder device. The patient experienced immediate subjective and
      hemodynamic improvement accompanied by rapid resolution of heart failure symptoms
      from New York Heart Association (NYHA) class IV to NYHA class II. This marked
      clinical improvement has been sustained at 9 months to date and 4-month follow-up
      echocardiography confirmed complete resolution of aortic regurgitation as the
      mechanism behind this improvement. 

PMID- 21183777
TI  - Thrombotic occlusion of a large septal perforator presenting as ST-segment
      elevation in V1-V2 and treated with aspiration thrombectomy: a brief review of
      the literature .
AB  - The interventricular septum constitutes approximately one-third of the mass of
      the left ventricle, and the bulk of the anterior septum is supplied by septal
      branches of the left anterior descending coronary artery. Ischemia of the
      interventricular septum results in angina, infarction, biventricular failure and
      ventricular arrhythmias. While the majority of septal infarctions are due to
      occlusions of the proximal left anterior descending coronary artery, a large
      first septal branch thrombosis can rarely be the culprit. Given the paucity of
      data pertaining to septal perforator disease, a thorough discussion on septal
      perforator coronary artery interventions and an illustrative case will be
      provided. 

PMID- 21183778
TI  - Anomalous right coronary artery origin from the pulmonary artery (ARCAPA)
      coexisting with obstructive atherosclerotic disease of the left coronary artery.
AB  - Coronary artery anomalies arising from the pulmonary artery are rare, result in
      reversed flow in the affected coronary artery, and are commonly associated with
      myocardial ischemia in infancy or childhood. Uncorrected survival to adult age is
      rare. We present a 77-year-old individual with anomalous right coronary artery
      from the pulmonary artery (ARCAPA), diagnosed by coronary angiography, whose
      clinical presentation was governed by coexisting obstructive atherosclerotic
      coronary disease. 

PMID- 21183779
TI  - Simulation and analysis of prismatic bioinspired compound lenses for solar cells:
      II. Multifrequency analysis.
AB  - Multifrequency numerical simulations of the light-coupling efficiency of a
      prismatic bioinspired compound lens (BCL) of silicon atop a thick silicon
      substrate were carried out within the framework of geometrical optics. Comparison
      was made with untextured and groove-textured silicon substrates as well as with
      untextured silicon substrates with a double-layer anti-reflection (DLAR) coating.
      Taking into account the broadband nature and the sea-level spectral irradiance of
      the insolation flux, and averaging over all admissible directions and both linear
      polarization states of the incident light, we found that the light-coupling
      efficiency can be almost doubled with respect to the untextured silicon substrate
      and enhanced by about a third with respect to a DLAR-coated untextured silicon
      substrate, by adopting a DLAR-coated silicon BCL.

PMID- 21183780
TI  - Arsenic: a potentially useful poison for Hedgehog-driven cancers.
AB  - Dysregulated Hedgehog (Hh) signaling has been implicated in a growing number of
      human cancers. To date, most antagonists of this signaling pathway that have been
      developed target the Hh receptor Smoothened. However, these are predicted to have
      minimal effect when the pathway is activated as a result of dysregulation
      downstream of this receptor. In this issue of the JCI, Beauchamp and colleagues
      provide preclinical evidence that arsenic trioxide, a drug FDA approved for the
      treatment of acute promyelocytic leukemia, inhibits the growth of Ewing sarcoma
      and medulloblastoma cells by targeting GLI family zinc finger (GLI) proteins,
      which are Hh signaling pathway components downstream of Smoothened.

PMID- 21183782
TI  - A stimulating way to improve T cell responses to poxvirus-vectored vaccines.
AB  - Vaccines remain one of the most cost-effective public health measures. Despite
      ongoing efforts, protective vaccines against cancer and many infectious diseases,
      including malaria, tuberculosis, and HIV/AIDS, are still not in hand. Most
      investigators believe that to succeed against these difficult targets, vaccines
      that generate potent T cell responses are needed. In this issue of the JCI, Salek
      Ardakani et al. show how the relative virulence of a virus/vaccine vector affects
      the memory CD8+ T cells generated and how the response may be enhanced. The work
      has important implications for the development of future vaccines that aim to
      trigger CD8+ T cell responses.

PMID- 21183781
TI  - No Kiss1ng by leptin during puberty?
AB  - Leptin exerts a permissive action on puberty by stimulating release of
      gonadotropin-releasing hormone (GnRH) in the hypothalamus. However, GnRH neurons
      lack leptin receptor (LepR), indicating that leptin must indirectly regulate
      these neurons. The Kiss1 gene produces kisspeptins that stimulate GnRH secretion.
      Because Kiss1 neurons express LepR and inactivation of Kiss1 causes
      hypogonadotropic hypogonadism, Donato et al., in this issue of the JCI, assessed
      whether deletion of LepR from Kiss1 neurons would prevent sexual maturation.
      Unexpectedly, mice lacking LepR in Kiss1 neurons had normal pubertal development
      and fertility. In contrast, deletion of LepR from the ventral premammillary
      nucleus, a region of the brain involved in sexual behavior, prevented puberty and
      fertility. These findings highlight the complex biology of leptin in
      reproduction.

PMID- 21183783
TI  - Chemokine antagonism in chronic hepatitis C virus infection.
AB  - Immune responses to hepatitis C virus (HCV) fail to clear the virus in most
      individuals. Why patients who are less likely to clear HCV infection have high
      plasma levels of CXCL10 (also known as IP-10), a chemokine that directs T cells
      to sites of infection, has long been unclear. In this issue of the JCI, Casrouge
      and colleagues shed light on this paradox by showing that CXCL10 in the plasma of
      many HCV patients is enzymatically processed to produce a CXCL10 receptor
      antagonist. These findings introduce a role for chemokine antagonism during HCV
      infection and unveil new avenues for improved HCV diagnosis and therapy.

PMID- 21183784
TI  - Charting the course across the blood-brain barrier.
AB  - The blood-brain barrier (BBB) presents a significant obstacle to delivery of
      targeted therapies to brain tumors. In this issue of the JCI, Staquicini and
      colleagues apply an in vivo phage-displayed library of random peptides to
      identify differentially expressed peptides that can be used to transport targeted
      agents across the intact BBB. The authors uncover a non-canonical, peptide
      mediated iron-mimicry mechanism to induce transport of the
      transferrin/transferrin receptor complex across the BBB. They then demonstrate
      the ability of phage-targeting approaches to deliver therapeutic cargo and
      molecular imaging reporters across the BBB in an intracranial glioblastoma mouse
      model.

PMID- 21183785
TI  - Cytokinesis failure and attenuation: new findings in Fanconi anemia.
AB  - The hallmarks of the rare inherited disorder Fanconi anemia (FA) are progressive
      bone marrow failure and susceptibility to cancer. The former is the major cause
      of death for patients with FA, as it usually occurs earlier in life than cancer
      development. Despite spectacular advances in unraveling the molecular details of
      FA, the origin of the bone marrow failure that is central to this condition for
      most patients has long been puzzling and controversial. Two studies recently
      published in the JCI, including one in this issue, will add to the debate. They
      also highlight the fact that studying rare disorders can elucidate important new
      clinical and biological principles.

PMID- 21183786
TI  - Gene defects in the soma: some get it and some don't!
AB  - Advances in DNA sequencing technologies have increased attention on genetic
      variation in somatic tissues. Although long known to cause neoplastic diseases,
      somatic variation is now being investigated as a pathogenetic mechanism for other
      diseases. Somatic changes are genomic DNA variations that were not inherited but
      arise in tissues throughout life. In this issue of the JCI, Magerus-Chatinet et
      al. explore somatic changes in patients with autoimmune lymphoproliferative
      syndrome (ALPS), a congenital disease of defective apoptosis and autoimmunity
      that is usually associated with germline heterozygous mutations in the gene
      encoding the Fas death receptor. They explain why certain individuals have severe
      disease manifestations by documenting somatic alterations in the germline normal
      FAS allele in an unusual population of "double-negative" T cells found in ALPS.
      Thus, the oncological concept of somatic loss of heterozygosity leading to
      selected cell expansion also applies to autoimmune diseases.

PMID- 21183787
TI  - Leptin's effect on puberty in mice is relayed by the ventral premammillary
      nucleus and does not require signaling in Kiss1 neurons.
AB  - Studies in humans and rodents indicate that a minimum amount of stored energy is
      required for normal pubertal development. The adipocyte-derived hormone leptin is
      a key metabolic signal to the neuroendocrine reproductive axis. Humans and mice
      lacking leptin or the leptin receptor (LepR) (ob/ob and db/db mice, respectively)
      are infertile and fail to enter puberty. Leptin administration to leptin
      deficient subjects and ob/ob mice induces puberty and restores fertility, but the
      exact site or sites of leptin action are unclear. Here, we found that genetic
      deletion of LepR selectively from hypothalamic Kiss1 neurons in mice had no
      effect on puberty or fertility, indicating that direct leptin signaling in Kiss1
      neurons is not required for these processes. However, bilateral lesions of the
      ventral premammillary nucleus (PMV) of ob/ob mice blunted the ability of
      exogenous leptin to induce sexual maturation. Moreover, unilateral reexpression
      of endogenous LepR in PMV neurons was sufficient to induce puberty and improve
      fertility in female LepR-null mice. This LepR reexpression also normalized the
      increased hypothalamic GnRH content characteristic of leptin-signaling
      deficiency. These data suggest that the PMV is a key site for leptin's permissive
      action at the onset of puberty and support the hypothesis that the multiple
      actions of leptin to control metabolism and reproduction are anatomically
      dissociated.

PMID- 21183788
TI  - Identification of SOX3 as an XX male sex reversal gene in mice and humans.
AB  - Sex in mammals is genetically determined and is defined at the cellular level by
      sex chromosome complement (XY males and XX females). The Y chromosome-linked gene
      sex-determining region Y (SRY) is believed to be the master initiator of male sex
      determination in almost all eutherian and metatherian mammals, functioning to
      upregulate expression of its direct target gene Sry-related HMG box-containing
      gene 9 (SOX9). Data suggest that SRY evolved from SOX3, although there is no
      direct functional evidence to support this hypothesis. Indeed, loss-of-function
      mutations in SOX3 do not affect sex determination in mice or humans. To further
      investigate Sox3 function in vivo, we generated transgenic mice overexpressing
      Sox3. Here, we report that in one of these transgenic lines, Sox3 was ectopically
      expressed in the bipotential gonad and that this led to frequent complete XX male
      sex reversal. Further analysis indicated that Sox3 induced testis differentiation
      in this particular line of mice by upregulating expression of Sox9 via a similar
      mechanism to Sry. Importantly, we also identified genomic rearrangements within
      the SOX3 regulatory region in three patients with XX male sex reversal. Together,
      these data suggest that SOX3 and SRY are functionally interchangeable in sex
      determination and support the notion that SRY evolved from SOX3 via a regulatory
      mutation that led to its de novo expression in the early gonad.

PMID- 21183789
TI  - The TNFR family members OX40 and CD27 link viral virulence to protective T cell
      vaccines in mice.
AB  - Induction of CD8+ T cell immunity is a key characteristic of an effective
      vaccine. For safety reasons, human vaccination strategies largely use attenuated
      nonreplicating or weakly replicating poxvirus-based vectors, but these often
      elicit poor CD8+ T cell immunity and might not result in optimal protection.
      Recent studies have suggested that virulence is directly linked to
      immunogenicity, but the molecular mechanisms underlying optimal CD8+ T cell
      responses remain to be defined. Here, using natural and recombinant vaccinia
      virus (VACV) strains, we have shown in mice that VACV strains of differing
      virulence induce distinct levels of T cell memory because of the differential use
      of TNF receptor (TNFR) family costimulatory receptors. With strongly replicating
      (i.e., virulent) VACV, the TNFR family costimulatory receptors OX40 (also known
      as CD134) and CD27 were engaged and promoted the generation of high numbers of
      memory CD8+ T cells, which protected against a lethal virus challenge in the
      absence of other mechanisms, including antibody and help from CD4+ T cells. In
      contrast, weakly replicating (i.e., low-virulence) VACV strains were poor at
      eliciting protective CD8+ T cell memory, as only the Ig family costimulatory
      receptor CD28 was engaged, and not OX40 or CD27. Our results suggest that the
      virulence of a virus dictates costimulatory receptor usage to determine the level
      of protective CD8+ T cell immunity.

PMID- 21183790
TI  - Tumor endothelin-1 enhances metastatic colonization of the lung in mouse
      xenograft models of bladder cancer.
AB  - Many patients with advanced bladder cancer develop lethal metastases to the lung.
      The vasoconstricting protein endothelin-1 (ET-1) has been implicated in this
      process, although the mechanism(s) by which it promotes metastasis remains
      unclear. Here, we have evaluated whether tumor ET-1 expression can serve as a
      biomarker for lung metastasis and whether it is required for metastatic disease.
      Evaluation of ET-1 mRNA and protein expression in four patient cohorts revealed
      that levels of ET-1 are higher in patients with muscle-invasive bladder cancers,
      which are associated with higher incidence of metastasis, and that high ET-1
      levels are associated with decreased disease-specific survival. Consistent with
      its proinflammatory activity, we found that tumor-derived ET-1 acts through
      endothelin-1 receptor A (ETAR) to enhance migration and invasion of both tumor
      cells and macrophages and induces expression of inflammatory cytokines and
      proteases. Using human and mouse cancer cells depleted of ET-1 and pharmacologic
      blockade of ET receptors in lung metastasis models, we found that tumor ET-1
      expression and ETAR activity are necessary for metastatic lung colonization and
      that this process is preceded by and dependent on macrophage infiltration of the
      lung. In contrast, tumor ET-1 expression and ETAR activity appeared less
      important in established primary or metastatic tumor growth. These findings
      strongly suggest that ETAR inhibitors might be more effective as adjuvant
      therapeutic agents than as initial treatment for advanced primary or metastatic
      disease.

PMID- 21183791
TI  - Spontaneous abrogation of the G2DNA damage checkpoint has clinical benefits but
      promotes leukemogenesis in Fanconi anemia patients.
AB  - DNA damage checkpoints in the cell cycle may be important barriers against cancer
      progression in human cells. Fanconi anemia (FA) is an inherited DNA instability
      disorder that is associated with bone marrow failure and a strong predisposition
      to cancer. Although FA cells experience constitutive chromosomal breaks, cell
      cycle arrest at the G2 DNA damage checkpoint, and an excess of cell death, some
      patients do become clinically stable, and the mechanisms underlying this, other
      than spontaneous reversion of the disease-causing mutation, are not well
      understood. Here we have defined a clonal phenotype, termed attenuation, in which
      FA patients acquire an abrogation of the G2 checkpoint arrest. Attenuated cells
      expressed lower levels of CHK1 (also known as CHEK1) and p53. The attenuation
      could be recapitulated by modulating the ATR/CHK1 pathway, and CHK1 inhibition
      protected FA cells from cell death. FA patients who expressed the attenuated
      phenotype had mild bone marrow deficiency and reached adulthood, but several of
      them eventually developed myelodysplasia or leukemia. Better understanding of
      attenuation might help predict a patient's clinical course and guide choice of
      treatment. Our results also highlight the importance of evaluating the cellular
      DNA damage checkpoint and repair pathways in cancer therapies in general.

PMID- 21183792
TI  - Arsenic trioxide inhibits human cancer cell growth and tumor development in mice
      by blocking Hedgehog/GLI pathway.
AB  - The Hedgehog (Hh) pathway is activated in some human cancers, including
      medulloblastoma. The glioma-associated oncogene homolog (GLI) transcription
      factors are critical mediators of the activated Hh pathway, and their expression
      may be elevated in some tumors independent of upstream Hh signaling. Thus,
      therapies targeting GLI transcription factors may benefit a wide spectrum of
      patients with mutations at different nodal points of the Hh pathway. In this
      study, we present evidence that arsenic trioxide (ATO) suppresses human cancer
      cell growth and tumor development in mice by inhibiting GLI1. Mechanistically,
      ATO directly bound to GLI1 protein, inhibited its transcriptional activity, and
      decreased expression of endogenous GLI target genes. Consistent with this, ATO
      inhibited the growth of human cancer cell lines that depended on upregulated GLI
      expression in vitro and in vivo in a xenograft model of Ewing sarcoma.
      Furthermore, ATO improved survival of a clinically relevant spontaneous mouse
      model of medulloblastoma with activated Hh pathway signaling. Our results
      establish ATO as a Hh pathway inhibitor acting at the level of GLI1 both in vitro
      and in vivo. These results warrant the clinical investigation of ATO for tumors
      with activated Hh/GLI signaling, in particular patients who develop resistance to
      current therapies targeting the Hh pathway upstream of GLI.

PMID- 21183795
TI  - Onset of autoimmune lymphoproliferative syndrome (ALPS) in humans as a
      consequence of genetic defect accumulation.
AB  - Autoimmune diseases develop in approximately 5% of humans. They can arise when
      self-tolerance checkpoints of the immune system are bypassed as a consequence of
      inherited mutations of key genes involved in lymphocyte activation, survival, or
      death. For example, autoimmune lymphoproliferative syndrome (ALPS) results from
      defects in self-tolerance checkpoints as a consequence of mutations in the death
      receptor-encoding gene TNF receptor superfamily, member 6 (TNFRSF6; also known as
      FAS). However, some mutation carriers remain asymptomatic throughout life. We
      have now demonstrated in 7 ALPS patients that the disease develops as a
      consequence of an inherited TNFRSF6 heterozygous mutation combined with a somatic
      genetic event in the second TNFRSF6 allele. Analysis of the patients' CD4(-)CD8(
      ) (double negative) T cells--accumulation of which is a hallmark of ALPS-
      revealed that in these cells, 3 patients had somatic mutations in their second
      TNFRSF6 allele, while 4 patients had loss of heterozygosity by telomeric
      uniparental disomy of chromosome 10. This observation provides the molecular
      bases of a nonmalignant autoimmune disease development in humans and may shed
      light on the mechanism underlying the occurrence of other autoimmune diseases.

PMID- 21183793
TI  - Systemic combinatorial peptide selection yields a non-canonical iron-mimicry
      mechanism for targeting tumors in a mouse model of human glioblastoma.
AB  - The management of CNS tumors is limited by the blood-brain barrier (BBB), a
      vascular interface that restricts the passage of most molecules from the blood
      into the brain. Here we show that phage particles targeted with certain ligand
      motifs selected in vivo from a combinatorial peptide library can cross the BBB
      under normal and pathological conditions. Specifically, we demonstrated that
      phage clones displaying an iron-mimic peptide were able to target a protein
      complex of transferrin and transferrin receptor (TfR) through a non-canonical
      allosteric binding mechanism and that this functional protein complex mediated
      transport of the corresponding viral particles into the normal mouse brain. We
      also showed that, in an orthotopic mouse model of human glioblastoma, a
      combination of TfR overexpression plus extended vascular permeability and ligand
      retention resulted in remarkable brain tumor targeting of chimeric adeno
      associated virus/phage particles displaying the iron-mimic peptide and carrying a
      gene of interest. As a proof of concept, we delivered the HSV thymidine kinase
      gene for molecular-genetic imaging and targeted therapy of intracranial
      xenografted tumors. Finally, we established that these experimental findings
      might be clinically relevant by determining through human tissue microarrays that
      many primary astrocytic tumors strongly express TfR. Together, our combinatorial
      selection system and results may provide a translational avenue for the targeted
      detection and treatment of brain tumors.

PMID- 21183794
TI  - Evidence for an antagonist form of the chemokine CXCL10 in patients chronically
      infected with HCV.
AB  - Chronic infection with hepatitis C virus (HCV) is a major public health problem,
      with nearly 170 million infected individuals worldwide. Current treatment for
      chronic infection is a combination of pegylated IFN-alpha2 and ribavirin (RBV);
      however, this treatment is effective in fewer than 50% of patients infected with
      HCV genotype 1 or 4. Recent studies identified the chemokine CXCL10 (also known
      as IP-10) as an important negative prognostic biomarker. Given that CXCL10
      mediates chemoattraction of activated lymphocytes, it is counterintuitive that
      this chemokine correlates with therapeutic nonresponsiveness. Herein, we offer
      new insight into this paradox and provide evidence that CXCL10 in the plasma of
      patients chronically infected with HCV exists in an antagonist form, due to in
      situ amino-terminal truncation of the protein. We further demonstrated that
      dipeptidyl peptidase IV (DPP4; also known as CD26), possibly in combination with
      other proteases, mediates the generation of the antagonist form(s) of CXCL10.
      These data offer what we believe to be the first evidence for CXCL10 antagonism
      in human disease and identify a possible factor contributing to the inability of
      patients to clear HCV.

PMID- 21183796
TI  - Short-,moderate-, and long-term treadmill training protocols reduce plasma,
      fundus, but not small intestine ghrelin concentrations in male rats.
AB  - BACKGROUND: It has been suggested that circulating ghrelin levels are upregulated
      by fasting, hypoglycemic status, and a physical exercise-induced energy deficit.
      AIM: The purpose of the present study was to investigate the timecourse
      adaptations of the plasma, fundus, and small intestine ghrelin concentrations as
      well as related hormones and liver ATP levels to 3, 6, and 12 weeks of treadmill
      endurance running. MATERIAL/SUBJECTS AND METHODS: Thirty-nine male Wistar rats
      (12-14 weeks old) were randomly assigned to 3 control (C3, no.=5; C6, no.=7 and
      C12, no.=7) and 3 training groups (E3, no.=6; E6, no.=7 and E12, no.=7). The rats
      in the 3 training groups were exercised on a motor-driven treadmill at 25 m/min
      (0% grade) for 60 min/day, 5 days/week for 3, 6, and 12 weeks, respectively. The
      animals were sacrificed 48 h after the last session of each training program and
      tissues were analyzed. RESULTS: Total ghrelin concentrations were significantly
      (p<0.05) lower in trained rat plasma and fundus tissue after all treadmill
      endurance running programs. Small intestine ghrelin concentrations remained
      unchanged. Plasma GH concentrations and liver ATP content were significantly
      higher in E6 and E12 groups. CONCLUSION: Data indicate that as little as 3 weeks
      of moderate treadmill exercise reduces plasma and fundus total ghrelin
      concentrations with elevated plasma GH and liver ATP content occurring after 6
      and 12 weeks of training. Exercise training-induced improvement of energy source
      availability and negative feedback from increased GH levels may play a role in
      reducing plasma and fundus ghrelin levels.

PMID- 21183826
TI  - Another great year in the making.

PMID- 21183827
TI  - Past, present, and future of head injury research.

PMID- 21183797
TI  - The Atg6/Vps30/Beclin 1 ortholog BEC-1 mediates endocytic retrograde transport in
      addition to autophagy in C. elegans.
AB  - Autophagy and endocytosis are dynamic and tightly regulated processes that
      contribute to many fundamental aspects of biology including survival, longevity,
      and development. However, the molecular links between autophagy and endocytosis
      are not well understood. Here, we report that BEC-1, the C. elegans ortholog of
      Atg6/Vps30/Beclin1, a key regulator of the autophagic machinery, also contributes
      to endosome function. In particular we identify a defect in retrograde transport
      from endosomes to the Golgi in bec-1 mutants. MIG-14/Wntless is normally recycled
      from endosomes to the Golgi through the action of the retromer complex and its
      associated factor RME-8. Lack of retromer or RME-8 activity results in the
      aberrant transport of MIG-14/Wntless to the lysosome where it is degraded.
      Similarly, we find that lack of bec-1 also results in mislocalization and
      degradation of MIG-14::GFP, reduced levels of RME-8 on endosomal membranes, and
      the accumulation of morphologically abnormal endosomes. A similar phenotype was
      observed in animals treated with dsRNA against vps-34. We further identify a
      requirement for BEC-1 in the clearance of apoptotic corpses in the hermaphrodite
      gonad, suggesting a role for BEC-1 in phagosome maturation, a process that
      appears to depend upon retrograde transport. In addition, autophagy genes may
      also be required for cell corpse clearance, as we find that RNAi against atg-18
      or unc-51 also results in a lack of cell corpse clearance.

PMID- 21183828
TI  - Infrapatellar bursitis: an occupational legacy.

PMID- 21183829
TI  - Deminan Caracaracol: a mythologic figure in Taino culture or an allegoric of Pott
      disease?

PMID- 21183831
TI  - Pachydermodactyly: an uncommon acquired digital fibromatosis.

PMID- 21183832
TI  - Omega 3 Chia seed loading as a means of carbohydrate loading.
AB  - The purpose of this study was to determine if Omega 3 Chia seed loading is a
      viable option for enhancing sports performance in events lasting >90 minutes and
      allow athletes to decrease their dietary intake of sugar while increasing their
      intake of Omega 3 fatty acids. It has been well documented that a high dietary
      carbohydrate (CHO) intake for several days before competition is known to
      increase muscle glycogen stores resulting in performance improvements in events
      lasting >90 minutes. This study compared performance testing results between 2
      different CHO-loading treatments. The traditional CHO-loading treatment served as
      the control (100% cals from Gatorade). The Omega 3 Chia drink (50% of calories
      from Greens Plus Omega 3 Chia seeds, 50% Gatorade) served as the Omega 3 Chia
      loading drink. Both CHO-loading treatments were based on the subject's body
      weight and were thus isocaloric. Six highly trained male subjects V(O2)max 47.8
      84.2 ml . kg(-1); mean (SD) of V(O2)max 70.3 ml . kg(-1) (13.3) performed a 1
      hour run at ~65% of their V(O2)max on a treadmill, followed by a 10k time trial
      on a track. There were 2 trials in a crossover counterbalanced repeated-measures
      design with a 2-week washout between testing sessions to allow the participants
      to recover from the intense exercise and any effects of the treatment. There was
      no statistical difference (p = 0.83) between Omega 3 Chia loading (mean 10k time
      = 37 minutes 49 seconds) and CHO loading (mean = 37 minutes 43 seconds). Under
      our conditions, Omega 3 Chia loading appears a viable option for enhancing
      performance for endurance events lasting >90 minutes and allows athletes to
      decrease their dietary intake of sugar while increasing their intake of Omega 3
      fatty acids but offered no performance advantages.

PMID- 21183833
TI  - Real-world impact of rotavirus vaccination.

PMID- 21183834
TI  - Impact of rotavirus vaccination on diarrhea-related hospitalizations among
      children < 5 years of age in Mexico.
AB  - BACKGROUND: Single-strain rotavirus vaccine was added to the national
      immunization program in Mexico in May 2007. We assessed the impact of vaccination
      on the number of diarrhea-related hospitalizations in Mexican children in 2008
      and 2009. METHODS: We obtained data on all-cause diarrhea-related
      hospitalizations from January 2003 to June 2009 in Mexican children <5 years of
      age. We compared diarrhea-related hospitalizations during the 2008 and 2009
      rotavirus seasons with the median number of diarrhea-related hospitalizations at
      baseline (2003-2006), before rotavirus vaccine introduction, at 306 Ministry of
      Health hospitals. We estimated vaccine coverage using administrative data.
      RESULTS: A median number of 10,993 diarrhea-related hospitalizations (range: 9877
      11958) occurred each prevaccine rotavirus season from 2003 to 2006 among children
      < 5 years of age. Diarrhea-related hospitalizations decreased by 11% (N = 9836)
      in 2008 and by 40% (N = 6597) in 2009. The greatest declines occurred in infants
      < 12 months of age during 2008 (25%) and 2009 (52%), with 1-dose rotavirus
      vaccination coverage of 74% and 89% during these years, respectively. A 43%
      decline was also noted among children 12 to 23 months of age during the 2009
      season. No declines were noted during either 2008 or 2009 among unvaccinated
      children >24 months of age during the study period. CONCLUSIONS: Marked declines
      in diarrhea-related hospitalizations among vaccine-eligible Mexican children < 24
      months of age have occurred during the first 2 complete rotavirus seasons
      following rotavirus vaccination. Rotavirus-specific surveillance and
      epidemiologic studies are necessary for a better understanding of the changes in
      disease epidemiology and public health impact from rotavirus vaccination.

PMID- 21183835
TI  - Reduction of diarrhea-associated hospitalizations among children aged < 5 Years
      in Panama following the introduction of rotavirus vaccine.
AB  - BACKGROUND: In March 2006, rotavirus vaccine (Rotarix, RV1) was introduced into
      the Panamanian national immunization program. We assessed the effect of vaccine
      on diarrhea-associated hospitalizations among young Panamanian children. METHODS:
      We obtained monthly numbers of diarrhea-associated hospitalizations among
      children aged <= 5 years during 2003 and 2008 from 5 health regions in Panama,
      representing 53% of the birth cohort. We compared the number of diarrhea
      associated hospitalizations during the postvaccine years of 2007 and 2008 with
      the prevaccine mean numbers 2003-2005 among children < 1 year and those 1 to 4
      years of age. Administrative data were used to estimate national rotavirus
      vaccine coverage. RESULTS: During prevaccine years, diarrhea-associated
      hospitalizations among children < 5 years in the 5 regions averaged 4057
      annually. After the vaccine introduction, a decrease in diarrhea-associated
      hospitalizations of 22% (898 fewer) occurred in 2007 and 37% (1502 fewer) in
      2008. Greater reductions were observed during January through June, the months
      presumed to have high rotavirus activity in prevaccine years (33% reduction in
      2007 and 58% in 2008, compared with prevaccine mean). Reduction estimates were
      similar among infants and those aged 1-4 years of age, even though only 25% of
      the latter group was likely to have received vaccine by early 2008. Estimated
      coverage with >= 1 dose of rotavirus vaccine among infants increased from 63% at
      the end of 2006 to 94% at the end of 2008. CONCLUSIONS: RV1 appears to have had a
      substantial impact on diarrhea-associated hospitalizations among young children
      in Panama.

PMID- 21183836
TI  - Rotavirus vaccines in Belgium: policy and impact.
AB  - BACKGROUND: : The current Belgian experience with rotavirus vaccination provides
      a unique perspective to look at the effect of vaccination. Shortly after
      introduction, a nation-wide recommendation was issued and despite the fact that
      both rotavirus vaccines are offered through partial reimbursement, vaccine uptake
      has already reached a high level (at least 90%). METHODS: : For the purpose of
      looking at the effectiveness of the Belgian rotavirus vaccination policy, 3 years
      after introduction, we retrospectively collated the publicly available data on
      the number of laboratory-confirmed rotavirus cases reported to a national network
      of sentinel laboratories during 1999 to 2010 and compared them with the available
      data on hospitalizations due to rotavirus gastroenteritis. RESULTS: : Both data
      sources (reported laboratory-diagnosed cases to a sentinel network as well as
      data on hospitalizations due to rotavirus gastroenteritis) show a decrease in the
      number of rotavirus infections and a 4- to 6-week delay in the onset of disease
      and the peak of incidence in the postvaccination period. CONCLUSIONS: : Because
      this decline coincides with the increased vaccine uptake and is sustained during
      consecutive rotavirus seasons, the effect is mainly attributed to the rotavirus
      vaccination. The rapid increase in vaccine coverage, despite the partial
      reimbursement for the vaccines, is remarkable. Continued postlicensure
      surveillance is necessary to further investigate the effectiveness of the
      vaccines and to document the public health impact of the vaccination in reducing
      disease burden.

PMID- 21183837
TI  - Reduction in rotavirus-associated acute gastroenteritis following introduction of
      rotavirus vaccine into Australia's National Childhood vaccine schedule.
AB  - INTRODUCTION: : Rotavirus vaccines were introduced into the funded Australian
      National Immunization Program (NIP) in July 2007. Due to purchasing arrangements,
      individual states and territories chose either a 2-dose RV1 (Rotarix, GSK)
      regimen or 3-dose RV5 (Rotateq, Merck/CSL) regimen. This allowed comparison of
      both vaccines in similar populations with high infant vaccination coverage.
      METHODS: : Admission and rotavirus identification data from the major pediatric
      hospitals in 3 states (2 using RV5, 1 RV1), together with state-based
      hospitalization and vaccination data from Queensland (RV5) were analyzed for the
      years before, and up to 30 months following rotavirus vaccine introduction.
      Emergency encounters and short-stay unit admissions for gastroenteritis are also
      described. RESULTS: : Rotavirus vaccine coverage in Australia is high, with 87%
      of infants receiving at least 1 dose. Hospital admissions for both rotavirus
      gastroenteritis and nonrotavirus-coded gastroenteritis were reduced following
      vaccine introduction in all states, not only for the age group eligible for NIP
      rotavirus vaccination, but also for children born prior. RV5 vaccine efficacy in
      Queensland has been estimated at 89.3%. Marked reductions in acute
      gastroenteritis emergency presentations and short-stay unit admissions have also
      been observed. CONCLUSIONS: : Early evidence from the NIP in Australia has
      demonstrated high rotavirus coverage with both RV1 and RV5. The introduction of
      both vaccines has been associated with a marked reduction in gastroenteritis
      admissions, supportive of both direct vaccine protection, as well as with
      indirect herd protection.

PMID- 21183838
TI  - Sustained decline in rotavirus detections in the United States following the
      introduction of rotavirus vaccine in 2006.
AB  - BACKGROUND: Following implementation of the rotavirus vaccination program in
      2006, rotavirus activity in the United States declined dramatically in 2007-2008
      but increased slightly in 2008-2009, despite greater vaccine uptake. To further
      evaluate impact of the vaccine program, we assessed trends in rotavirus testing
      and detection during 2009-2010. METHODS: We examined rotavirus testing data from
      July 2000 to June 2010 from the National Respiratory and Enteric Viruses
      Surveillance System to compare rotavirus season timing and peak activity in the
      pre- and postvaccine introduction eras. Rotavirus season onset was defined as the
      first of 2 consecutive weeks during which the percentage of specimens testing
      positive for rotavirus was >= 10%. To assess trends in rotavirus testing and
      detection, we restricted the analyses to 25 laboratories that reported for >= 26
      weeks per season from 2000 to 2010. RESULTS: During 2009-2010, the threshold for
      the start of the rotavirus season was never achieved nationally or in the North,
      Midwest, or West. Activity in the South met this threshold but the season
      duration was substantially shorter and of lower magnitude than in all previous
      pre- and postvaccine introduction seasons. Nationally and within each region, the
      peak week was more delayed and the peak proportion of positive tests was
      substantially lower than all previous seasons. The total number of tests
      performed declined by 23%, and the number of positive tests declined by 86%.
      CONCLUSIONS: Rotavirus activity was substantially diminished during the 2009-2010
      rotavirus season compared with the prevaccine baseline and the 2 previous
      postvaccine introduction seasons. These sustained declines over 3 rotavirus
      seasons reaffirm the health benefits of the US rotavirus vaccination program.

PMID- 21183839
TI  - United States rotavirus strain surveillance from 2005 to 2008: genotype
      prevalence before and after vaccine introduction.
AB  - BACKGROUND: A live, attenuated rotavirus vaccine, RotaTeq(r), was approved in
      2006 for immunization of infants in the United States. To monitor the
      distribution of rotavirus genotypes before and after vaccine introduction, the
      Centers for Disease Control and Prevention conducted strain surveillance with the
      National Rotavirus Strain Surveillance System. METHODS: Over 3 rotavirus seasons,
      2005-2006, 2006-2007, and 2007-2008, National Rotavirus Strain Surveillance
      System laboratories collected rotavirus-positive stool specimens and submitted
      them to the Centers for Disease Control and Prevention. Rotavirus strains were G-
      and P-genotyped by multiplex reverse transcription-polymerase chain reaction or
      nucleotide sequencing. RESULTS: During 2005-2006 and 2006-2007 seasons, G1 was
      the dominant G-type but in the 2007-2008 season, G3 replaced G1 as the most
      frequently detected strain. Four genotypes, G1P[8], G2P[4], G3P[8], and G9P[8]
      were detected in every season. Uncommon strains observed during the study period
      were G2P[8], G1P[6], G2P[6], G4P[6], G1P[4], G3P[9], G12P [6], and G12P[8]. The
      mean age of rotavirus cases in the 2007-2008 season increased significantly in
      patients less than 3 years old compared with the 2 previous seasons. CONCLUSIONS:
      : The increased overall prevalence of G3P [8] strains in 2007-2008, the first
      rotavirus season with reasonable rotavirus vaccine coverage, was consistent with
      Australian reports of G3 dominance following RotaTeq introduction. However, these
      strain changes in both countries have occurred in the context of large declines
      in severe rotavirus disease and we cannot rule out that they are simply the
      result of naturally occurring changes in rotavirus strain prevalence. These
      findings underscore the need for careful monitoring of strains to assess possible
      vaccine pressure-induced changes and vaccine effectiveness against various
      rotavirus genotypes.

PMID- 21183840
TI  - Distribution of rotavirus genotypes after introduction of rotavirus vaccines,
      Rotarix(r) and RotaTeq(r), into the National Immunization Program of Australia.
AB  - BACKGROUND: Rotavirus vaccines, RotaTeq and Rotarix, were introduced into the
      Australian National Immunization Program on July 1, 2007. The simultaneous
      introduction in different Australian states and territories provides a unique
      opportunity to compare the affect of each vaccine on the types of circulating
      rotavirus strains. This report describes the rotavirus genotypes responsible for
      the hospitalization of children during the first 2-year period after vaccine
      introduction. METHODS: A total of 764 rotavirus-associated diarrheal cases were
      collected from children presenting to hospital in 10 Australian centers.
      Rotavirus genotype was determined using reverse transcription polymerase chain
      reaction assays. RESULTS: G1P[8] was the dominant genotype nationally (52%),
      followed by G2P[4] (19.8%), G9P[8] (12.2%), and G3P[8] (11%). Differences in the
      prevalence rates of G2P[4] and G3P[8] were seen in the various states. G2P[4]
      strains were more prevalent in states using Rotarix, whereas G3P[8] strains were
      more prevalent in states using RotaTeq. CONCLUSIONS: Differences in rotavirus
      genotypes were observed across Australia, which suggest that different immune
      pressures are exerted by the different vaccines, but do not necessarily imply
      lack of protection by either vaccine. These differences may simply be related to
      the variation that can occur because of natural annual fluctuation in rotavirus
      strain prevalence.

PMID- 21183841
TI  - Remarkable postvaccination spatiotemporal changes in United States rotavirus
      activity.
AB  - Analyses of US laboratory surveillance data during 1991 to 2004 established
      annual peak rotavirus activity occurred first in the Southwest and last in the
      Northeast. We compared spatiotemporal patterns during the 2 years preceding
      vaccine introduction in 2006 with the first 2 years following introduction. The
      postvaccine introduction years failed to demonstrate the typical Southwest to
      Northeast spread of rotavirus activity.

PMID- 21183842
TI  - Uptake, impact, and effectiveness of rotavirus vaccination in the United States:
      review of the first 3 years of postlicensure data.
AB  - BACKGROUND: Rotavirus vaccine was recommended for routine use in US infants in
      2006. Before the introduction of vaccine, rotavirus was the most common cause of
      severe gastroenteritis in children <5 years of age in the United States. METHODS:
      We reviewed published data to summarize the US experience during the first 3
      years of its rotavirus vaccination program. RESULTS: Rotavirus seasons have been
      delayed and diminished in magnitude during the postvaccine era compared with the
      prevaccine era. Hospitalizations, emergency department visits, and outpatient
      visits due to gastroenteritis have declined dramatically in children < 5 years of
      age including in children age-ineligible to have received vaccine, suggesting
      indirect benefits of vaccination. Rotavirus vaccine has been widely accepted by
      pediatricians. Vaccine coverage is steadily increasing but remains lower than
      coverage levels of other routine infant immunizations. CONCLUSIONS: The
      implementation of routine childhood immunization against rotavirus has rapidly
      and dramatically reduced the large health burden of rotavirus gastroenteritis in
      US children. Continued monitoring of rotavirus diarrhea is needed to determine if
      immunity wanes as vaccinated children get older and to better quantify the
      indirect benefits of vaccination. Ongoing surveillance will also enable
      monitoring of the long-term impact of vaccination on rotavirus epidemiology.

PMID- 21183843
TI  - Progress in the introduction of the rotavirus vaccine in Latin America and the
      Caribbean: four years of accumulated experience.
AB  - BACKGROUND: Two effective and safe rotavirus vaccines became available in 2006
      and have been recommended for use in all countries by the World Health
      Organization. This article provides an update on the use of rotavirus vaccine in
      Latin American and Caribbean (LAC) countries. METHODS: Data reported by LAC
      countries to the Pan American Health Organization (PAHO) were reviewed. RESULTS:
      As of May 2010, 14 LAC countries and 1 territory have introduced the rotavirus
      vaccine into their national expanded program on immunization (EPI). Reported
      coverage levels for rotavirus vaccine are lower than those for other EPI vaccines
      recommended at the same age. A total of 15 LAC countries are part of the PAHO's
      LAC rotavirus surveillance network; 12 of them are using the vaccine. LAC
      countries are conducting several studies on rotavirus vaccine effectiveness, cost
      effectiveness, and monitoring safety. Also, LAC countries are generating lessons
      learned on the public health implications of introducing a new vaccine into the
      EPI. Nine countries and the Cayman Islands pay for the entire cost of the vaccine
      using government funds. All but 2 countries purchase their rotavirus vaccine
      through PAHO's Revolving Fund. CONCLUSIONS: Rotavirus vaccine introduction in LAC
      has been faster than for other new vaccines, but coverage levels need to increase
      to maximize the effect of the intervention. Rotavirus surveillance needs to
      expand and be strengthened to better assess the effect of vaccine use. LAC
      countries will continue to provide useful data to monitor rotavirus trends and
      vaccine effect.

PMID- 21183844
TI  - The superiority of minimally invasive parathyroidectomy based on 1650 consecutive
      patients with primary hyperparathyroidism.
AB  - OBJECTIVE: To compare the results of minimally invasive parathyroidectomy (MIP)
      and conventional parathyroid surgery. BACKGROUND: Primary hyperparathyroidism is
      a common endocrine disorder often treated by surgical intervention. Outpatient
      MIP, employing image-directed focused exploration under cervical block
      anesthesia, has replaced traditional surgical approaches for many patients with
      primary hyperparathyroidism. This retrospective review of a prospective database
      compared MIP with conventional parathyroid surgery. METHODS: One thousand six
      hundred fifty consecutive patients underwent surgery for primary
      hyperparathyroidism by a single surgeon between 1990 and 2009 at 2 tertiary care
      academic hospitals. Conventional bilateral cervical exploration under general
      anesthesia was performed in 613 patients and MIP was performed in 1037 cases.
      Cure rates, complication rates, pathologic findings, length of hospital stay, and
      total hospital costs were compared. RESULTS: Minimally invasive parathyroidectomy
      is associated with improvements in the cure rate (99.4%) and the complication
      rate (1.45%) compared to conventional exploration with a cure rate of 97.1% and a
      complication rate of 3.10%. In addition, the hospital length of stay and total
      hospital charges were also improved compared to conventional surgery.
      CONCLUSIONS: Minimally invasive parathyroidectomy is a superior technique and
      should be adopted for the majority of patients with sporadic primary
      hyperparathyroidism.

PMID- 21183846
TI  - Novel approaches to perioperative assessment and intervention may improve long
      term outcomes after colorectal cancer resection in older adults.
AB  - Colorectal cancer (CRC) is common among older adults and surgical resection with
      curative intent is the primary treatment of CRC. Despite the changing
      demographics of CRC patients and increasing prevalence of multiple comorbidities,
      surgery is increasingly performed in this complex aging population. Clinically
      important short-term outcomes have improved for this population, but little is
      known about long-term outcomes. We review the literature to evaluate trends in
      CRC surgery in the geriatric population and the outcomes of surgical treatment.
      We explore the specific gaps in understanding longitudinal patient-centered
      outcomes of CRC treatment. We then propose adaptations from the geriatrics
      literature to better predict both short and long-term outcomes after CRC surgery.
      Interventions, such as prehabilitation, coupled with comprehensive geriatric
      assessment may be important future strategies for identifying vulnerable older
      patients, ameliorating the modifiable causes of vulnerability, and improving
      patient-centered longitudinal outcomes. Further research is needed to determine
      relevant aspects of geriatric assessments, identify effective intervention
      strategies, and demonstrate their validity in improving outcomes for at-risk
      older adults.

PMID- 21183845
TI  - The importance of assessing both inpatient and outpatient surgical quality.
AB  - OBJECTIVE: We aimed to determine whether hospital-level surgical performance was
      similar across outpatient and inpatient settings. BACKGROUND: The majority of
      surgical procedures in the United States are performed in an outpatient setting
      but most quality improvement focuses on inpatient care. METHODS: Using data from
      the 2006 to 2008 American College of Surgeons- National Surgical Quality
      Improvement Program, risk-adjusted hospital observed to expected ratios for
      morbidity and mortality were compared for inpatient and outpatient cases. In
      addition, hospital outpatient performance in each year was compared with
      performances in subsequent years. RESULTS: Hospitals demonstrated variation in
      outcomes for outpatient morbidity with both good and poor outliers in each year.
      Outpatient mortality was so rare as to not support robust modeling. There was a
      lack of congruence between hospital performance for outpatient morbidity and
      either inpatient morbidity or inpatient mortality in each year, indicating that
      inpatient performance is not interchangeable with outpatient performance.
      Outpatient morbidity performance correlation between years was only moderate
      (correlations 0.449-0.534, all P < 0.001) indicating that although outcomes from
      1 year mildly predict subsequent years, substitution of data would likely lead to
      missed opportunities for improvement. CONCLUSIONS: Assessments of risk-adjusted
      hospital-level outpatient morbidity performance demonstrate (1) variability
      across American College of Surgeons- National Surgical Quality Improvement
      Program sites; (2) a lack of congruence between outpatient morbidity performance
      and either inpatient morbidity or mortality performance; (3) year-to-year
      variation of outpatient morbidity performance at individual institutions.
      Continuing evaluation of both outpatient and inpatient outcomes is supported.
      Given the substantial volume of outpatient care delivered, outpatient assessments
      are likely to be an important component of ongoing quality improvement efforts.

PMID- 21183847
TI  - AmbLOXe--an epidermal lipoxygenase of the Mexican axolotl in the context of
      amphibian regeneration and its impact on human wound closure in vitro.
AB  - OBJECTIVE: The Mexican axolotl (Ambystoma mexicanum) is a well-characterized
      example for intrinsic regeneration. As lipoxygenase signaling is of crucial
      importance to scarless mammalian wound healing, we postulated that lipoxygenases
      might be expressed during amphibian regeneration and they might also influence
      human cells under appropriate conditions. In this study we identified an
      amphibian lipoxygenase and evaluated its impact on human cells in an in vitro
      wound model. METHODS: cDNA encoding for amphibian epidermal lipoxygenase
      (AmbLOXe) was polymerase chain reaction amplified and sequenced followed by
      phylogenic classification based on T-coffee alignment. Distribution of AmbLOXe
      was examined in various Ambystoma tissues, using polymerase chain reaction and in
      situ hybridization. Lipoxgenase influence was investigated using an outgrowth
      model of amphibian epidermal cells. Human osteosarcoma, as well as keratinocyte
      cell lines expressing AmbLOXe, were tested concerning in vitro wound closure in a
      monolayer scratch model. RESULTS: We isolated AmbLOXe from Ambystoma limb bud
      blastema identified as a homologue of human epidermal lipoxygenase. Amphibian
      epidermal lipoxygenase is expressed in Axolotl limb blastema and in epidermal
      cells which show decreased cell migration and proliferation rates when treated
      with LOX inhibitors. Furthermore, human osteosarcoma and keratinocyte cells
      showed increased rates of cell migration if transfected with AmbLOXe. CONCLUSION:
      In this study, AmbLOXe, a new effector of amphibian regeneration is described. In
      consideration of the presented data, AmbLOXe is important for amphibian epidermal
      cell proliferation and migration. As AmbLOXe expressing human osteosarcoma and
      keratinocyte cell lines showed increased rates of in vitro wound closure, an
      influence of amphibian mediators on human cells could be described for the first
      time.

PMID- 21183848
TI  - Minilaparoscopic versus conventional laparoscopic cholecystectomy a systematic
      review and meta-analysis.
AB  - OBJECTIVE: This review broadly examines the impact of minilaparoscopic versus
      conventional laparoscopic cholecystectomy. The primary outcome was failure of
      surgical technique. The secondary outcomes were to examine adverse events,
      cosmesis, length of time to return to activity, quality of life, and length of
      operation. METHODS: Five databases, 2 conference proceedings, reference lists of
      retrieved articles, and a Web-based trial registry were searched to identify
      eligible studies. Experts in the field of laparoscopic surgery were also
      contacted to provide information for the review.This systematic review and meta
      analysis were conducted in accordance with the QUORUM guidelines. RESULTS:
      Eighteen studies met eligibility criteria. Methodologic quality was unclear in
      most trials. Patients having a minilaparoscopic technique had higher conversion
      rates than patients having a conventional laparoscopic technique [OR 2.25 (1.18
      4.30)]. Although minilaparoscopic surgeries were converted, more often there was
      not a trend toward increased conversion to an open technique. There was a trend
      toward fewer adverse events using a minilaparoscopic technique [0.57 (0.31
      1.04)], however it was not significant. Cosmesis was improved in minilaparoscopic
      patients at 1 month [mean difference -0.74(-1.09 to -0.38)]. Patients receiving
      minilaparoscopic procedures returned to activity quicker [mean difference -0.74 (
      1.23-0.25)]. CONCLUSIONS: Further randomized trials are needed to determine
      whether minilaparoscopic techniques truly offer any advantages. Important patient
      outcomes such as failure of technique, adverse events, cosmesis, and quality of
      life should be emphasized to determine whether there is any benefit over
      conventional laparoscopic cholecystectomy.

PMID- 21183849
TI  - Increased short- and long-term mortality at low-volume pediatric heart transplant
      centers: should minimum standards be set? Retrospective data analysis.
AB  - OBJECTIVE: The relationship between volume and outcome in many complex surgical
      procedures is well established. BACKGROUND: No published data has examined this
      relationship in pediatric cardiac transplantation, but low-volume adult heart
      transplant programs seem to have higher early mortality. METHODS: The United
      Network for Organ Sharing (UNOS) provided center-specific data for the 4647
      transplants performed on patients younger than 19 years old, 1992 to 2007.
      Patients were stratified into 3 groups based on the volume of transplants
      performed in the previous 5 years at that center: low [<19 transplants, n = 1135
      (24.4%)], medium [19-62 transplants, n = 2321(50.0%)], and high [>=63
      transplants, n= 1191 (25.6%)]. A logistic regression model for postoperative
      mortality was developed and observed-to-expected (O:E) mortality rates calculated
      for each group. RESULTS: Unadjusted long-term survival decreased with decreasing
      center volume (P<0.0001). Observed postoperative mortality was higher than
      expected at low-volume centers [O:E ratio 1.39, 95% confidence interval (CI) 1.05
      1.83]. At low volume centers, high-risk patients (1.34, 0.85-2.12)--especially
      patients 1 year old or younger (1.60, 1.07-2.40) or those with congenital heart
      disease (1.36, 0.94-1.96)--did poorly, but those at high-volume centers did well
      (congenital heart disease: 0.90, 0.36-1.26; age<1 year: 0.75, 0.51-1.09). Similar
      results were obtained in the subset of patients transplanted after 1996. In
      multivariate logistic regression modeling, transplantation at a low-volume center
      was associated with an odds ratio for postoperative mortality of 1.60 (95% CI,
      1.14-2.24); transplantation at a medium volume center had an odds ratio of 1.24
      (95% CI, 0.92-1.66). CONCLUSION: The volume of transplants performed at any one
      center has a significant impact on outcomes. Regionalization of care is one
      option for improving outcomes in pediatric cardiac transplantation.

PMID- 21183850
TI  - Optimizing medical response to large-scale disasters: the ad hoc collaborative
      health care system.

PMID- 21183851
TI  - Portal vein thrombosis and liver transplantation: evolution during 10 years of
      experience at the University of Bologna.
AB  - OBJECTIVE: To evaluate the evolution of liver transplantation (LT) in cases with
      partial and total portal vein thrombosis (PVT). BACKGROUND: Portal vein
      thrombosis and in particular total PVT are still surgically demanding conditions,
      which can exclude patients from LT or increase the postoperative complications
      after LT. METHODS: We reviewed our 10-year experience (first era 1998-2002 and
      second era 2003-2008), comparing the outcome of patients with PVT to a group
      without PVT. RESULTS: Among 889 LTs, we intraoperatively diagnosed 91 PVTs
      (10.2%):51 partial PVTs (56%) and 40 total PVTs (44%). The rate of complete PVTs
      increased from the first to the second era (2.2% vs. 6.7%, P < 0.005). Partial
      PVTs were mainly treated with thrombectomy while complete PVTs were managed with
      thrombectomy in 26 cases (63%), jumping graft in 6 (15%), portocaval
      hemitransposition in 6 (15%), and anastomosis to varix in 3 (7%). Among cases of
      PVT and no-PVT, the postoperative mortality was comparable (6.6% vs. 5.8%), as
      were the 1- and 5-year patient survival rates (85% and 68% PVT vs. 86% and 73%
      non-PVT). The postoperative outcome was similar in the PVT group between patients
      with partial and complete PVT, but in this last group, patient survival differed
      significantly between the 1st and 2nd era (57% vs. 89% at 1 year, P < 0.05).
      CONCLUSIONS: Liver transplantation offers good survival in patients with partial
      PVT but also in selected cases with total PVT, where surgical innovation has
      improved the results.

PMID- 21183852
TI  - High concentrations of dichloroacetate have minor effects on the vitality of the
      mammalian nerve fibers: an ex-vivo electrophysiological study.
AB  - Dichloroacetate has been used extensively in the treatment of cancer and genetic
      mitochondrial diseases, but there have been reports of dichloroacetate-induced
      peripheral neuropathy. In this study, the acute effects of sodium dichloroacetate
      on the peripheral nerve fibers were investigated, using an ex-vivo preparation,
      in the isolated sciatic nerve of the rat. The amplitude of the evoked nerve
      compound action potential (CAP) was measured to confirm the proper functioning of
      the nerve fibers. The half-vitality time [the time required to decrease the CAP
      to 50% of its initial value, here called inhibitory time 50% (IT50)], of the
      nerve fibers, which had been incubated in normal saline, was 30.4 +/- 0.26 h
      (n=12). When the nerve fibers were incubated in 10 mmol/l of dichloroacetate, the
      IT50 was 29.7 +/- 0.34 h (n=8), with no significant difference from the control
      (P>0.05). The fact that such a high concentration of dichloroacetate as 10 mmol/l
      had no effect on the parameters of the evoked CAP is an indication of the high
      tolerance of peripheral nerve fibers to this compound. When a concentration of 20
      mmol/l of dichloroacetate was tested, a 15.2 +/- 1.25% (n=12) inhibition in the
      CAP amplitude occurred, but although a relatively small population of nerve
      fibers was inactive, the vitality of the remaining active axons was not affected,
      with a final IT50 of 28.1 +/- 0.64 h (n=12), with no significant difference from
      the IT50 of the control, which for this group of experiments was 28.1 +/- 0.17 h
      (P>0.05). This moderate effect, with a 15.2 +/- 1.25% decrease in the CAP
      amplitude, suggests that within the exposure limitation of the sciatic nerve
      preparation of 28-30 h, there could be a gradual development of certain
      biochemical changes leading to the early stages of dichloroacetate-induced
      neurotoxicity.

PMID- 21183854
TI  - Takotsubo syndrome.
AB  - The Takotsubo Syndrome was first described by Japanese investigators
      approximately 20 years ago and has been increasingly recognized in all countries.
      It occurs almost exclusively in postmenopausal women and is triggered by a severe
      emotional stress. Severe chest pain is common and the electrocardiogram often
      mimics that seen with an acute myocardial infarction. An echocardiogram or a left
      ventriculogram resembles a Takotsubo, a Japanese octopus fishing pot. In Japanese
      'Takotsubo' means a 'fishing pot for trapping octopus.' These traps have a round
      bottom with a narrow neck. When the octopus enters the Takotsubo it is most often
      trapped while the fisherman pulls the device to the surface. The syndrome is
      reversible and over the next several weeks to months all electrocardiographic and
      echocardiographic changes revert to normal. It is likely that the emotionally
      induced catecholamine surge in an estrogen-deficient woman causes a combination
      of epicardial coronary artery constriction, constriction of the myocardial
      microvasculature, and direct cardiomyocyte toxicity producing a temporary
      stunning effect on the left ventricular myocardium.

PMID- 21183855
TI  - Breast and stomach cancer incidence and survival in migrants in the Netherlands,
      1996-2006.
AB  - Migrant populations experience a health transition that influences their cancer
      risk, determined by environmental changes and acculturation processes. In this
      retrospective cohort study, we investigated differences in breast and stomach
      cancer risk and survival in migrants to the Netherlands. Invasive breast and
      stomach cancer cases diagnosed between 1996 and 2006 were selected from the
      Netherlands Cancer Registry. Standardized incidence ratios (SIR) were computed as
      the ratio of observed and expected cancers. Differences in the survival were
      expressed as hazard ratio (HR) using Cox regression and relative survival rates
      (RSR). All migrant women exhibited a significantly lower risk for breast cancer
      compared with Dutch natives. However, 5-year RSR was lower in all migrants (range
      68-73%) compared with Dutch natives (85%). Death rates were increased in Moroccan
      [HR = 1.2 (1.0-1.5)] and reduced in Indonesian [HR = 0.8 (0.8-0.9)] patients with
      breast cancer. The incidence of noncardia stomach cancer was significantly
      elevated in all migrants, being highest in Turkish males [SIR = 1.9 (1.6-2.3)].
      Cardia stomach cancer was less frequent in all migrants, being lowest in
      Surinamese males [SIR = 0.3 (0.2-0.6)]. Death rates for stomach cancer were lower
      in patients from Morocco [HR = 0.6 (0.4-0.9)], whereas 1-year RSR for stomach
      cancer was better in all migrant groups. Both lower breast cancer rates and
      higher stomach cancer rates point to a strong link between environmental
      exposures, behavioural patterns and cancer risk during the life course.
      Favourable risks in migrants should be sustained as long as possible whereas
      survival disparities require careful monitoring and counteraction with preventive
      means as well as improved access to healthcare.

PMID- 21183853
TI  - Isolated clinical hypertension diagnosis: self-home BP, ambulatory BP monitoring,
      or both simultaneously?
AB  - Self-blood pressure (BP) measurement (SBPM) and ambulatory BP measurement (ABPM)
      are suitable for the isolated clinical hypertension (ICH) or 'white-coat'
      hypertension diagnosis. However, patients with ICH have a different
      cardiovascular risk according to the measurement technique used for the
      diagnosis. OBJECTIVE: To describe baseline cardiovascular risk of patients with
      hypertension and with ICH according to SBPM and daytime ABPM. METHODS: Six
      hundred and sixty-four newly diagnosed and never treated patients with
      hypertension and with an average age of 59.3 years (standard deviation=12.0) were
      included (52% men) in this study. Clinical data, analytical data with urinary
      albumin excretion rate, estimated glomerular filtration rate, retinography, SBPM,
      and ABPM were performed. Cardiovascular risk was estimated from the European
      Society of Hypertension and Systemic Coronary Risk Evaluation tables. RESULTS:
      ICH prevalence varies according to the ambulatory measurement technique used:
      SBPM=24.2%, daytime ABPM=8.1, and 5.2% if criteria are required from both
      techniques. In the 403 patients with hypertension and who had SBPM and ABPM, the
      percentage of patients with high or very high baseline cardiovascular risk, falls
      progressively from 31.2% of patients with sustained hypertension to 20.0% of
      patients with ICH measured using SBPM, to 15.1% of patients with ICH measured
      using ABPM-day and to 9.5% of patients who present ICH using both techniques
      (P<0.005 for trend). CONCLUSION: The baseline results show that patients with
      hypertension and with ICH using SBPM and daytime ABPM are those who have a lower
      baseline cardiovascular risk and allow ICH to be defined on the basis of normal
      ambulatory readings using both techniques.

PMID- 21183856
TI  - Predictive value of NT-proBNP for cardioversion in a new onset atrial
      fibrillation.
AB  - OBJECTIVE: To detect the clinical use of N-terminal pro B-type natriuretic
      peptide (NT-proBNP) values for predicting cardioversion in a new onset atrial
      fibrillation (AF) in the emergency department. METHODS: NT-proBNP was measured in
      200 patients admitted to the emergency department, in the observational unit with
      primary diagnosis of a new onset AF (<2 weeks). Cohort was divided into rate
      control and rhythm-control groups according to the strategy used by the admitting
      physician. Patients treated with electric cardioversion were excluded. Primary
      endpoint was conversion to sinus rhythm during hospital admission. RESULTS: In
      rhythm and rate controls, NT-proBNP was lower in patients who restored sinus
      rhythm (P<0.001). Same result was observed even when logistic regression was used
      to adjust for differences at baseline clinical characteristics. NT-proBNP of less
      than 450 pg/ml was associated with cardioversion in both the groups (likelihood
      ratio of 0.19 for rate control, and 0.27 for rhythm control) whereas a value of
      more than 1800 pg/ml was associated with persistent AF at discharge (likelihood
      ratio of 2.02 and 2.01, respectively). CONCLUSION: In the acute setting of a new
      onset AF, NT-proBNP seems to predict cardioversion in rate-control and rhythm
      control strategies when it is less than 450 pg/ml or more than 1800 pg/ml. In
      this ranges of values it might help to allocate resources and plan for patient
      admission and further management. There is a grey area (450-1800 pg/ml) in which
      NT-proBNP did not seem to be clinically useful.

PMID- 21183857
TI  - Effect of intravenous mannitol in mobilization of resistant cirrhotic ascites.
AB  - INTRODUCTION: Cirrhotic ascites is conventionally treated with bed rest, salt
      restriction, and diuretics. In 20-30% of patients it eventually became resistant
      to diuretic therapy partly because of reduced sodium excretion owing to the
      development of resistance against atrial natriuretic peptide. Diuretics
      resistance can be overcome partially by increasing distal tubular sodium delivery
      by atrial natriuretic peptide and mannitol administration. OBJECTIVES: To
      determine the short-term response of intravenous mannitol administration on
      mobilization of resistant cirrhotic ascites in addition to conventional diuretic
      treatment. STUDY DESIGN: It was an interventional, experimental (double-blind
      randomized controlled) study conducted in the medical department of Jinnah
      Hospital, Lahore. A total of 60 patients meeting inclusion and exclusion criteria
      were included in the study, 30 each in mannitol and placebo groups. Patients were
      followed for 5 days after the administration with mannitol or placebo. Main
      outcome measures were increase in 24 h urinary sodium, increase in urinary
      volume, decrease in weight and abdominal girth. RESULTS: Data showed that all the
      parameters of response, that is increase in 24 h urinary sodium (cases 34.09+/
      16.71 vs. control 19.16+/-13.22, P=0.000), increase in urinary volume (cases
      260.00+/-73.58 vs. control 91.67+/-43.71) decrease in weight (cases 3.07+/-1.14
      vs. control 2.3+/-1.08, P=0.010) and decrease in abdominal girth (cases 4.70+/
      2.86 vs. control 2.07+/-1.41, P=0.000) on day 5 of treatment were in favor of
      mannitol administration. CONCLUSION: This study shows that resistant ascites can
      be initially mobilized by infusion of mannitol. The long-term benefits of such
      therapy are unknown.

PMID- 21183858
TI  - Endoscopic ultrasound-guided fine-needle aspiration biopsy in the evaluation of
      bile duct strictures and gallbladder masses: a systematic review and meta
      analysis.
AB  - STUDY OBJECTIVES: Recently, there are very few research on endoscopic ultrasound
      guided fine needle aspiration (EUS-FNA) of bile duct and gallbladder masses. The
      objective of this study was to assess the overall diagnostic accuracy of EUS-FNA
      in the evaluation of patients with bile duct strictures and gallbladder masses
      with a meta-analysis. METHODS: The MEDLINE, EMBASE, Cancerlit and Cochrane
      Library, and other database, from January 1995 to July 2010, were searched for
      studies evaluating EUS-FNA accuracy. Meta-analysis methods were used to obtain
      pooled estimates of sensitivity, specificity, diagnostic odds ratio, summary
      receiver operating characteristic curves, and the Q* index. RESULTS: A total of
      nine studies with 284 patients, who fulfilled all the inclusion criteria, were
      considered for the analysis. EUS-FNA had a pooled sensitivity of 0.84 (95%
      confidence interval: 0.78-0.88) and a pooled specificity of 1.00 (95% confidence
      interval: 0.94-1.00). Overall area under the curve was 0.9254, The Q* index was
      0.8598 and the calculated diagnostic odds ratio was 75.1. No complications
      occurred. CONCLUSION: EUS-FNA was an accurate and safe tool in the evaluation
      bile duct and gallbladder masses. High-quality prospective studies regarding EUS
      FNA in the evaluation of patients with bile duct and gallbladder masses are still
      needed to be conducted.

PMID- 21183859
TI  - Swimming upstream? Patient Protection and Affordable Care Act and the cultural
      ascendancy of public health.

PMID- 21183860
TI  - Defining fast-growing melanomas: reappraisal of epidemiological, clinical, and
      histological features.
AB  - The growth rate (GR) of melanomas is not uniform. A fast-growing subtype has been
      identified and seems to have a role in the stabilization of the mortality rates
      because of melanoma. To examine features associated with fast-growing melanomas
      (FGMs) and to determine the relationship between the GR and well-recognized
      prognostic factors of melanoma, a series of 386 new invasive cutaneous melanomas
      seen during 2004-2009 were retrieved from our database. The GR was calculated
      according to earlier published studies. FGMs were defined as those whose GR was
      greater than 0.49 mm per month. Differences in clinical, epidemiological, and
      pathological features were evaluated. Correlations between the GR, tumor
      thickness, and mitotic rate were also analyzed. FGMs were significantly more
      prevalent among patients aged over 65 years and with a higher rate of past
      personal history of nonmelanoma skin cancer. This subtype was over-represented
      among melanomas located on both nonexposed and usually exposed skin and was less
      related to earlier sunburns. Patients with FGMs presented with more aggressive
      pathological features and had more advanced disease with sentinel node analysis
      affected in up to 35% of cases. There was a strong positive correlation between
      the GR and tumor thickness (r=0.762), and mitotic rate (r=0.542). This study was
      limited by being retrospective in nature. FGMs are a highly aggressive subtype of
      melanomas that seem to develop after at least two routes, one related to chronic
      sun exposure and another unrelated to the sun. Older patients have a higher
      predisposition to develop this kind of tumor. This variant warrants specific
      strategies to improve primary and secondary prevention.

PMID- 21183861
TI  - Introduction of rapid tests for large-scale syphilis screening among female,
      male, and transgender sex workers in Mumbai, India.
AB  - BACKGROUND: Despite widespread availability of rapid plasma reagin (RPR) for
      syphilis screening at sex worker (SW)-dedicated project clinics, uptake of
      syphilis testing remains low and prevalence of syphilis remains high among SWs in
      Maharashtra, India. The primary reasons given for refusal of RPR were fear of
      venipuncture and long waiting times for results. METHODS: Between December 2007
      and February 2008, rapid point of contact diagnostic tests (Syphicheck-WB,
      Qualpro Diagnostics, India) using finger-prick samples were introduced for
      syphilis screening, with RPR confirmation test of positives. RESULTS: Uptake of
      syphilis screening among clinic attenders increased to 63.1% compared with an
      average of 14.3% before the intervention. Among the 19,809 SWs who were screened,
      598 tested positive (3% prevalence of lifetime infection). Of these, 395 (66.1%)
      accepted RPR confirmation test; 337 (88.3%) were seroreactive, 160 (40.5%) had
      titers >=1:8 (active syphilis). The projected overall prevalence of active
      syphilis among all SWs screened was 1.2% but varied by site and typology of sex
      work (brothel-based, 2.4%; bar-based, 0.5%; street-based, 2.3%; male SWs, 0.2%;
      transgender, 11.3%; home-based, 0.6%). CONCLUSIONS: The introduction of rapid
      tests dramatically increased the uptake of syphilis screening in this large-scale
      intervention among a high-risk population in India. However, only two-thirds of
      SWs with a positive rapid test accepted a confirmatory RPR test. The high
      proportion (40.5%) of active syphilis among those testing positive on the rapid
      screening test justifies treatment even if confirmatory testing is declined. A
      commercially available, simple, rapid nontreponemal test is needed to further
      strengthen syphilis screening.

PMID- 21183862
TI  - The tale of two serologic tests to screen for syphilis--treponemal and
      nontreponemal: does the order matter?
AB  - BACKGROUND: Standard syphilis screening involves an initial screening with a
      nontreponemal test and confirmation of positives with a treponemal test. However,
      some laboratories have reversed the order. There is no detailed quantitative and
      qualitative evaluation for the order of testing. In this study, we analyzed the
      health and economic outcomes of the order of testing for the 2 serologic tests
      used in syphilis screening under pure screening settings. METHODS: We used a
      cohort decision analysis to examine the health and economic outcomes of the
      screening algorithms for low and high prevalence settings. The 2-step algorithms
      were nontreponemal followed by treponemal (Nontrep-First) and treponemal followed
      by nontreponemal (Trep-First). We included the 1-step algorithms (treponemal only
      [Trep-Only] and an on-site nontreponemal only [Nontrep-Only]) for comparison. We
      estimated overtreatment rates and the number of confirmatory tests required for
      each algorithm. RESULTS: For a cohort of 10,000 individuals, our results
      indicated that the overtreatment rates were substantially higher (more than 3
      times) for the 1-step algorithms, although they treated a higher number of cases
      (over 15%). The 2-step algorithms detected and treated the same number of
      individuals. Among the 2-step algorithms, the Nontrep-First was more cost
      effective in the low prevalence setting ($1400 vs. $1500 per adverse outcome
      prevented) and more cost-saving ($102,000 vs. $84,000) in the high prevalence
      setting. CONCLUSIONS: The difference in cost was largely due to the substantially
      higher number of confirmatory tests required for the Trep-First algorithm,
      although the number of cases detected and treated was the same.

PMID- 21183863
TI  - Reasons for not HIV testing, testing intentions, and potential use of an over-the
      counter rapid HIV test in an internet sample of men who have sex with men who
      have never tested for HIV.
AB  - BACKGROUND: Correlates of main reasons for not HIV testing, HIV testing
      intentions, and potential use of an over-the-counter rapid HIV test (OTCRT) among
      men who have sex with men who have never tested for HIV (NTMSM) are unknown.
      METHODS: We evaluated these correlates among 946 NTMSM from 6 US cities who
      participated in an internet-based survey in 2007. FINDINGS: Main reasons for not
      testing were low perceived risk (32.2%), structural barriers (25.1%), and fear of
      testing positive (18.1%). Low perceived risk was associated with having fewer
      unprotected anal intercourse (UAI) partners and less frequent use of the internet
      for HIV information; structural barriers were associated with younger age and
      more UAI partners; fear of testing positive was associated with black and
      Hispanic race/ethnicity, more UAI partners, and more frequent use of the internet
      for HIV information. Strong testing intentions were held by 25.9% of all NTMSM
      and 14.8% of those who did not test because of low perceived risk. Among NTMSM
      who were somewhat unlikely, somewhat likely, and very likely to test for HIV,
      47.4%, 76.5%, and 85.6% would likely use an OTCRT if it was available,
      respectively. CONCLUSIONS: Among NTMSM who use the internet, main reasons for not
      testing for HIV vary considerably by age, race/ethnicity, UAI, and use of the
      internet for HIV information. To facilitate HIV testing of NTMSM, programs should
      expand interventions and services tailored to address this variation. If
      approved, OTCRT might be used by many NTMSM who might not otherwise test for HIV.

PMID- 21183864
TI  - Chlamydia trachomatis and Neisseria gonorrhoeae transmission from the female
      oropharynx to the male urethra.
AB  - In a sexually transmitted disease clinic-based sample of men who have sex with
      women, positivity for urethral Chlamydia trachomatis and Neisseria gonorrhoeae
      was 3.5% and 3.1%, respectively, among patients whose only urethral exposure in
      the previous 3 months was receiving fellatio from a woman. Urethral infections
      acquired by fellatio might contribute to ongoing disease spread.

PMID- 21183865
TI  - Screening for acute human immunodeficiency virus infection in Baltimore public
      testing sites.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) RNA testing of pooled HIV antibody
      negative specimens can identify acute HIV infection (AHI) and trigger
      interventions to reduce transmission during this highly infectious period.
      METHODS: A Baltimore, MD program serving sexually transmitted disease clinics and
      other high-risk sites combined HIV testing by third-generation enzyme immunoassay
      (EIA) with RNA testing of pooled antibody-negative specimens. Laboratory and
      Disease Intervention Specialists' records were reviewed for program evaluation. A
      cost analysis was performed. RESULTS: In 22 months, we tested 60,695 specimens
      for HIV. Of these, 1766 (2.9%) tested positive by EIA. Pooled HIV RNA testing of
      58,925 EIA-negative specimens detected 7 cases of AHI (0.01%). Reflex HIV RNA
      testing of EIA-reactive, Western blot-indeterminate specimens confirmed 4
      additional AHI cases (total AHI, 0.02%). Contact tracing detected no additional
      previously unknown cases of HIV infection. CONCLUSIONS: The utility of pooled HIV
      RNA testing may be limited by advances in HIV testing technology that reduce the
      seronegative window period and by characteristics of the local HIV epidemic.

PMID- 21183866
TI  - Medications to reduce cardiovascular risk after kidney transplantation.

PMID- 21183867
TI  - Subcapsular fetal pig pancreas fragment transplantation provides normal blood
      glucose control in a preclinical model of diabetes.
AB  - OBJECTIVE: Identifying a limitless source of beta-cells that survive
      transplantation into a neovascularised site and provide normal blood glucose
      control remains an important goal in the development of pancreatic islet
      xenotransplantation. It was our hypothesis that fetal porcine pancreas fragments
      could achieve these objectives, and this was tested in a large preclinical animal
      model. RESEARCH DESIGN AND METHODS: Inbred "Westran Pig" fetal porcine pancreas
      fragments were transplanted beneath the splenic capsule into syngeneic Westran
      Pig recipients without immunosuppression, and 3 months later, a total native
      pancreatectomy was performed to demonstrate function. RESULTS: Histologic
      analysis showed appropriate development of islet-like structures up to and beyond
      120 days after transplantation. After native pancreatectomy, recipients survived
      more than 100 days without exogenous insulin and with normal glucose homeostasis
      as assessed by normal glucose tolerance tests, K values, and normal glucagon
      secretion. CONCLUSIONS: This study confirms that fetal pig islet tissue has the
      potential to mature and function normally in a neovascularised site, hence,
      avoiding the innate immune destruction that occurs when islet tissue is exposed
      directly to the circulation.

PMID- 21183868
TI  - miRNA regulation of liver growth after 50% partial hepatectomy and small size
      grafts in rats.
AB  - BACKGROUND: The molecular mechanisms underlying the growth of small size grafts
      and the remaining livers are poorly understood. MicroRNAs (miRNAs) negatively
      modulate expression of genes that are involved in cellular function and
      metabolism. The aim of this study is to identify critical miRNA species that
      modulate the growth of small grafts and the remaining livers after partial
      hepatectomy (PH). METHODS: Small size graft liver transplantation was performed
      in rats. Liver tissue was harvested after transplant or PH for the determination
      of miRNA expression profile, and the data were confirmed by quantitative reverse
      transcriptase polymerase chain reaction. The genes involved in cell cycle and
      proliferation were analyzed by quantitative reverse-transcriptase polymerase
      chain reaction and immunohistochemical staining. RESULTS: Compared with control
      liver, miR_122a, Let_7b, and miR_26a were reduced by more than 90% in 45% volume
      grafts. In the remaining livers after 50% PH, 30 miRNAs were down-regulated by
      more than 50%, and among them, miR_22a, miR_26a, miR_30b, Let_7f, and Let_7g were
      markedly decreased. A negative correlation existed between down-regulated miRNAs
      and highly up-regulated genes involved in cell cycle and proliferation in the
      remaining livers. Moreover, overexpression of miR_26a markedly down-regulated
      cyclin E2 protein levels and significantly decreased proliferation of HepG2
      cells. CONCLUSION: Down-regulated miRNAs play a pivotal role in promoting the
      growth of small size grafts and the remaining livers. The negative correlation
      between down-regulated miRNAs and up-regulated genes suggests that these specific
      miRNAs participate in the modulation of a growth response in both living donors
      and small size graft recipients.

PMID- 21183869
TI  - T Lymphocyte responses to nonpolymorphic HLA-derived peptides are associated with
      chronic renal allograft dysfunction.
AB  - BACKGROUND: The routine assessment of cellular alloimmunity to guide therapy is
      of perennial interest because this limb of the immune system is the main target
      of current transplant immunosuppression. That this has not as yet been realized
      in clinical practice reflects the difficulty of developing a standardized assay
      that accounts for the high degree of polymorphism exhibited by histocompatibility
      antigens. METHODS: We have investigated whether immune responses to peptides
      derived from nonpolymorphic regions of human leukocyte antigen arise after
      transplantation, in particular in those with chronic allograft dysfunction.
      RESULTS: Peripheral blood mononuclear cell gamma-interferon production to
      peptides derived from the nonpolymorphic alpha3 domain of class 1 human leukocyte
      antigen occurred more frequently in long-term renal transplant recipients than
      healthy controls (51/110 vs. 1/18, 46.3% vs. 5.5%; P<0.001). These responses were
      associated with chronic allograft dysfunction manifested by a reduced and
      decreasing estimated glomerular filtration rate (responders vs. nonresponders:
      39.5 vs. 48.8 mL/min, P=0.015 and -4.1 vs. -1.3 mL/min/year, P=0.008). Responses
      occurred mostly to autologous, "cryptic self-epitopes" and arose from
      CD4CD25CD127 T lymphocytes, which have been previously implicated in chronic
      rejection. CONCLUSION: These findings suggest a strategy for assessing cellular
      immune responses to transplantation antigens with potential for generalization.

PMID- 21183870
TI  - A randomized study comparing IGL-1 to the University of Wisconsin preservation
      solution in liver transplantation.
AB  - BACKGROUND: Institut Georges Lopez-1 (IGL-1) is a new preservation solution with
      lower potassium and lower viscosity than University Wisconsin solution (UW).
      These characteristics which improve liver preservation lead us to evaluate
      clinical effects of IGL-1 in a randomized controlled study with UW.
      MATERIAL/METHODS: From June 2007 to July 2009, after exclusion of partial graft,
      combined transplantation and fulminant hepatic failure, 140 deceased donor
      allografts were randomly assigned to IGL-1 (n=48) or UW (n=92) solution.
      Variables concerning donors and recipients were collected including liver tests
      (total serum bilirubin, prothrombin time and transaminases) were analyzed until
      postoperative day 30. Incidences of hepatic artery thrombosis (HAT), primary non
      function (PNF) and biliary non anastomotic strictures (NAS) were analyzed. The
      comparative analysis of costs was realized. RESULTS: Donor and recipients
      characteristics were similar in both groups. Volume of preservation solution
      utilized for harvesting was identical. Duration of cold ischemia (472+/-142 vs.
      477+/-122 min), surgery (427+/-97 vs. 437+/-94 min) and proportion of extended
      criteria donor was similar. Postoperative kinetic and level liver tests were
      similar. Rate of PNF (2% vs. 4%), early retransplantation (6% vs. 7%), incidence
      of biliary NAS (2% vs. 3%) and HAT (6% vs. 4%) were similar. Mean intensive care
      unit (ICU) stay was similar (5.6 vs. 6.1 days). However costs related to
      preservation solution for one liver procurement were 992.0 for IGL-1 vs. 1609.0
      Euros for UW. CONCLUSIONS: Results of this randomized study shows that the
      efficacy and safety of IGL-1 are comparable to those of the reference UW with a
      lower cost.

PMID- 21183871
TI  - Effect of the ICAM1 and VCAM1 gene polymorphisms on delayed graft function and
      acute kidney allograft rejection.
AB  - BACKGROUND: Immunological response following renal transplantation is a result of
      ischemia and reperfusion injury, which increase ICAM-1 and VCAM-1 endothelial
      expression. Reports suggest that there are genetic variations in ICAM-1 and VCAM
      1 synthesis that can contribute to delayed graft function (DGF) and acute renal
      rejection after kidney transplantation. The aim of this study was to examine the
      effect of ICAM1 and VCAM1 gene polymorphisms on the early period after kidney
      transplantation. MATERIAL/METHODS: The study enrolled 270 Caucasian renal
      transplant recipients (166 males, 104 females). METHODS: Genotyping of the rs5498
      ICAM1 and the rs1041163 and rs3170794 VCAM1 gene polymorphisms was performed
      using real-time PCR. RESULTS: The distribution of genotypes and alleles of the
      studied polymorphisms in patients with DGF and without DGF showed no
      statistically significant differences. The risk of acute rejection was
      significantly higher in patients with the rs5498 ICAM1 GG genotype than in
      carriers of the AG and AA genotypes (OR 3.01; 95% CI 1.51-6.00, p=0.003).
      CONCLUSIONS: These results suggest that ICAM1 and VCAM1 gene polymorphisms play a
      minor role in pathogenesis of DGF. The rs5498 ICAM1 gene polymorphism is
      associated with increased risk of acute rejection of kidney allografts.

PMID- 21183872
TI  - Pentostatin as rescue therapy for glucocorticoid-refractory acute and chronic
      graft-versus-host disease.
AB  - BACKGROUND: Despite scientific advances in hematopoietic cell allografting,
      glucocorticoid-refractory acute (aGVHD) and chronic graft-versus-host disease
      (cGVHD) represent major sources of transplant-related morbidity and mortality. We
      aimed to characterize the activity of pentostatin as rescue therapy for
      refractory GVHD. MATERIAL/METHODS: In a retrospective analysis, we examined the
      activity of pentostatin as rescue therapy of glucocorticoid-refractory acute and
      chronic GVHD. RESULTS: In 12 patients with advanced (overall aGVHD grade III/IV
      in 8/12) refractory aGVHD, overall response (ORR) was achieved in 6/12, and
      complete remission (CR) of aGVHD in 4/12 allowing additional rescue
      immunosuppressive agents. Median overall survival (OS) was 1.4 months (95% CI:
      0.26-2.4). Causes of death included refractory aGVHD and infection. In 18
      patients with refractory cGVHD (12/18 with severe cGVHD), pentostatin induced CR
      in 1/18, and partial response (PR) in 9/18. Activity was observed in all affected
      organs. The median decrease in glucocorticoid therapy over 24 months after
      pentostatin initiation for refractory cGVHD was 38% (range=0-100%). Median OS was
      5 months (95% CI: 1.6 - NR). CONCLUSIONS: Allowing for the utilization of
      additional immune suppressive agents, this series suggests the activity of
      pentostatin as rescue therapy of refractory GVHD.

PMID- 21183873
TI  - Prevention of hyperacute xenograft rejection through direct thrombin inhibition
      with hirudin.
AB  - BACKGROUND: Hyperacute xenograft rejection (HXR) is characterized by complement
      activation and intravascular thrombosis. The pathogenesis of HXR is attributed to
      antibodies binding to alpha-Gal-epitopes on the endothelial cells (EC) of the
      xenograft, activating complement and thrombin-mediated coagulation mechanisms.
      Our aim was to evaluate the influence of thrombin inhibition upon HXR and tissue
      integrity in an ex-vivo working heart model. MATERIAL/METHODS: Eighteen isolated
      porcine hearts were perfused with human whole blood in a working heart model. The
      blood was treated with heparin (n=9) in group G-I and with heparin and
      additionally recombinant hirudin (0.012 mg/ml bolus, afterwards 4.5 ug/ml/h
      continuously) in group G-II (n=9). The experiments were terminated at end of
      cardiac output. Histological analysis was performed after the experiments.
      RESULTS: Working heart time of G-II was significantly longer (712.0+/-37.8 vs.
      125.0+/-31.4 min, p<0.01). Heart weight increase in G-II was lower (0.05+/-0.01
      vs. 0.30+/-0.06%/min, p<0.01). Stroke work index and specific coronary flow
      improved significantly in G-II after 120 minutes. Histological analysis revealed
      increased tissue damage and thrombosis phenomena in G-I. Moreover,
      immunohistochemistry showed increased C3 and C5b-C9 upon EC of G-I. CONCLUSIONS:
      Direct thrombin inhibition with Hirudin could be a successful strategy in primate
      xenotransplantation experiments to prevent tissue damage thus improving the graft
      survival.

PMID- 21183874
TI  - Influence of CYP2C19 genotypes on graft pathological findings and postoperative
      liver function in recipients after living-donor liver transplantation.
AB  - BACKGROUND: New graft cytochrome P450 2C19 (CYP2C19) should have different
      characteristics after living-donor liver transplantation (LDLT). We prospectively
      investigated the influence of genotypes of CYP2C19 in liver graft pathological
      finding (GPF) and postoperative liver function (POLF) of recipients after LDLT.
      MATERIAL/METHODS: Among 60 consecutive patients who underwent LDLT, 36 recipients
      developed sudden-onset abnormal liver function and required liver biopsy, while
      the remaining 24 recipients did not require biopsy. LDLT recipient blood samples
      were genotyped for CYP2C19 variants, and recipients were categorized as
      homozygous extensive metabolizers (HomEM), heterozygous extensive metabolizers
      (HetEM), and poor metabolizers (PM). RESULTS: The acute rejection rate was 15.0%
      (9/60). There were 4 characteristics of GPF when abnormal POLF occurred. Logistic
      regression analysis showed that the risk estimate of abnormal POLF was 26.7 times
      higher for LDLT recipients with the CYP2C19 HomEM genotype as compared to the PM
      genotype, and 5.0 times higher for LDLT recipients with the HomEM genotype as
      compared to the HetEM genotype. A linear trend relationship was found between the
      incidence of abnormal POLF and the CYP2C19 genotype. CONCLUSIONS: These results
      suggest that the speed of drug metabolism as characterized by the CYP2C19
      genotype (HomEM > HetEM > PM) may affect the outcome after LDLT; thus, CYP2C19
      genotyping may be valuable for predicting abnormal POLF with different GPF after
      LDLT.

PMID- 21183875
TI  - Use of an aberrant right hepatic artery arising from the superior mesenteric
      artery of the recipient for arterial reconstruction in liver transplantation.
AB  - BACKGROUND: Our aim was to report a single centre experience of using a
      recipient's aberrant right hepatic artery (RHA) from the superior mesenteric
      artery (SMA) to establish inflow into liver allografts. MATERIAL/METHODS: All
      patients who had arterial reconstruction with an aberrant RHA were identified
      from a prospective database (1989-2004). Indications and outcomes were evaluated,
      with particular reference to arterial complications. RESULTS: An aberrant RHA was
      used in 27/2518 recipients (1%), including 6 paediatric recipients. Indications
      were replaced CHA (4), hypoplastic CHA (7), atheroma (12), previous conduit (1)
      and poor post-anastomotic flow (3). After a median of 42 months, arterial
      complications occurred in 2 paediatric recipients (hepatic artery thrombosis 1;
      arterial stenosis 1). Four patients developed anastomotic biliary strictures, and
      one paediatric recipient developed ischaemic cholangiopathy after hepatic artery
      thrombosis. Two patients underwent retransplantation (one patient with arterial
      stenosis). 1-year and 5-year patient survival rates were 85% and 81%. There were
      6 deaths unrelated to vascular complications. CONCLUSIONS: In adult liver
      transplant recipients with an unsuitable common hepatic artery, an aberrant right
      hepatic artery may be used to establish arterial inflow. This technique may be
      associated with a higher rate of vascular complications in paediatric recipients,
      and should be used cautiously in this group.

PMID- 21183876
TI  - Liver repopulation by transplanted hepatocytes in a rat model of acute liver
      failure induced by carbon tetrachloride and a partial hepatectomy.
AB  - BACKGROUND: Although hepatocyte transplantation holds great promise, most of the
      transplanted hepatocytes fail to proliferate in the liver without any
      manipulation of the host. Previous studies have shown that the replacement of the
      host liver cells with transplanted hepatocytes, called "liver repopulation",
      requires a combination of proliferative stimuli to the transplanted hepatocytes
      and suppression of the host hepatocytes. This study explored whether liver
      repopulation could be achieved by hepatocyte transplantation in a chemically and
      surgically induced-liver failure model in the rat. MATERIAL/METHODS: Dipeptidyl
      peptidase IV-positive (DPPIV +) Fisher rats were used as donor and syngeneic
      DPPIV-deficient (DPPIV-) rats served as recipient. The recipient rats were
      treated with carbon tetrachloride (CCl4) for 4 weeks followed by a 68% partial
      hepatectomy (PH) and transplantation of the hepatocytes (HT). Five groups were
      established based on the influence of specific factors including CCl4, PH, and
      HT. The liver regeneration rates were evaluated by the liver weight/body weight
      (LW/BW) ratio. The liver repopulation rates were determined by the formula;
      (DPPIV+ cell counts/all cell counts) *100%. RESULTS: The liver regeneration rates
      were 3.5 and 2.6 in the rats with CCl4+PH, and PH alone, respectively (P<0.01).
      In the rats with CCl4+PH, DPPIV positive cell clusters appeared in the host liver
      parenchyma 7 days after HT (day 7), exhibiting continuous proliferation up to day
      28 (The liver repopulation rates were 1.1% and 13.4%, respectively, p<0.05).
      CONCLUSIONS: Liver repopulation by hepatocyte transplantation was therefore found
      to be possible in partially hepatectomized rats under the continuous exposure to
      regulated doses of CCl4.

PMID- 21183877
TI  - Students of the Polish catholic theological seminars and the issue of organ
      transplantation.
AB  - BACKGROUND: The aim of the paper was the analysis of the stance and knowledge of
      the religious seminars alumni, about the legal foundations of transplantology.
      MATERIAL/METHODS: The study group were 204 alumni of the five senior religious
      seminars in Poland. By the use of an anonymous questionnaire, the clerics were
      interviewed. The questionnaire consisted of thirteen questions concerning the
      issue of organ transplants in Poland. RESULTS: It can be concluded that the
      attitude of clerics towards the organ transplantation is no different in
      principle from the attitude of the general public. Noteworthy is the fact that
      clerics often declared their consent to be donors of organs for transplantation.
      Attitudes of the clerics are also characterized by the fact that they did not
      object to procurement of organs of people close to them after their death.
      However, it can be concluded, that the attitude of surveyed clerics reflects a
      negative trend associated with a greater focus on receiving an organ in time of
      danger (95%), than the willingness to donating their organs after death (80%).
      CONCLUSIONS: The level of knowledge of the legal conditions of transplantation
      among the students of catholic seminars is increasing. Clerics are aware of the
      role of future educators, despite the fact that in majority of religious seminars
      there was no consent of the Deans to perform such survey.

PMID- 21183878
TI  - Booster of plerixafor can be successfully used in addition to chemotherapy-based
      regimen to rescue stem cell mobilization failure.
AB  - BACKGROUND: Autologous stem cell transplantation (autoSCT) is currently
      considered one of the standard approaches in the treatment of patients suffering
      from multiple myeloma and recurrent or relapsed lymphomas. Unfortunately, a
      significant proportion of those patients fail to mobilize minimum CD34+ cell dose
      to undergo this procedure. Here we present the strategy that allows to rescue the
      outcome of ongoing unsuccessful chemotherapy based mobilizations. CASE REPORT:
      All five patients failed to release satisfactory number of CD34+ cells to
      peripheral blood after chemotherapy plus G-CSF-based mobilization regimen,
      despite raise in leukocytosis. In this situation, we decided to administer a
      booster of plerixafor, a specific CXCR4 receptor inhibitor. We observed rapid 2.6
      to 16-fold increase of peripheral blood CD34+ cells number that allowed to start
      aphereses in all cases. Consequently, all five patients who would not otherwise
      collect required number of CD34+ cells, collected above 2.0*106 CD34+ cells/kg
      that allowed for hematopoietic stem cell transplantation. CONCLUSIONS: We would
      like to suggest that poor mobilizers could be rescued with the timely addition of
      plerixafor, thus they can avoid another procedure of stem cell mobilization.

PMID- 21183879
TI  - Liver transplantation with ABO incompatible graft under immunoadsorption protocol
      -case report.
AB  - BACKGROUND: ABO incompatible liver transplantation is still controversial, but
      accepted in selected cases. Recently several authors reported use of the new
      technology aimed at elimination anti-donor ABO specific hemagglutinins to assist
      immunosuppression in preventing acute rejection after transplantation. CASE
      REPORT: We report two cases of liver transplantation in children with ABO
      incompatible graft under immunoadsorption protocol. Both patients were
      transplanted urgently (one due to acute decompensation of chronic liver failure
      and second due to acute liver failure) with ABO incompatible liver grafts. Both
      patients were in very poor general condition with deterioration of neurological
      status and there were no suitable ABO compatible grafts at the time. In both
      cases immunosuppressive protocol consisted of induction with basiliximab,
      followed by tacrolimus, mycophenolate mofetil and corticosteroids. Additionally
      in both patients 3 immunoadsorption sessions with Glycosorb ABO(r) system
      (Glycorex AB, Sweden), were performed. There were no any acute rejection episodes
      till now. The only problem observed after transplantation was mild anemia due to
      low grade hemolysis in the postoperative period. Both patients are alive and well
      with very good liver function 20 and 26 months after transplantation.
      CONCLUSIONS: Immunoadsorption therapy can be safely and effectively introduced in
      recipients of ABO incompatible donor liver.

PMID- 21183880
TI  - Simultaneous Clostridium difficile-associated colitis and late-onset intestinal
      cytomegalovirus disease in a renal transplant recipient.
AB  - BACKGROUND: Infection remains the most common complication following renal
      transplantation (RT). Cytomegalovirus (CMV) is one of the most important
      pathogens in this patient population and Clostridium difficile-associated colitis
      (CDAC) has emerged as one of the most frequent gastrointestinal complications.
      Only few cases of simultaneous CMV enterocolitis and CDAC have been reported.
      CASE REPORT: A 73-year-old woman who underwent RT more than 10 years earlier
      developed severe abdominal pain and profound bloody diarrhea. She was diagnosed
      with simultaneous CMV enterocolitis and CDAC and treated with ganciclovir and
      metronidazole. She was unable to clear the infections and underwent colonic and
      small bowel resection, but ultimately died from indirect complications following
      the two severe infections. CONCLUSIONS: Late-onset CMV disease in this patient
      who was CMV negative prior to transplantation and received a CMV-negative graft
      was an unexpected event; the simultaneous occurrence of CDAC aggravated the
      clinical picture ultimately leading to surgery, graft failure and death.
      Clinicians should be aware that opportunistic infections may develop many years
      post transplant and may occur simultaneously.

PMID- 21183881
TI  - Geographic differences in disease expression of cryptococcosis in solid organ
      transplant recipients in the United States.
AB  - BACKGROUND: Whether there are geographic differences in clinical presentation of
      cryptococcosis in solid organ transplant (SOT) recipients in the United States
      (US) is not known. MATERIAL/METHODS: Patients comprised a cohort of 120 SOT
      recipients from US transplant centers who fulfilled the EORTC/MSG criteria for
      cryptococcal disease. RESULTS: Central nervous system, pulmonary, and cutaneous
      cryptococcal disease were observed in 51% (61/120), 64% (77/120), and 15%
      (18/120) of the patients, respectively. Cutaneous disease was documented in 9%
      (3/32) of the patients from South Atlantic region, 19% (6/32) from Mid Atlantic,
      26% (6/23) from Southern, 7% (2/29) from Midwestern, and in 1 of 4 patients from
      the Northwestern region of the US. When controlled for age, immunosuppressive
      regimen, type of transplant, and renal failure at baseline, patients from the
      Southern compared with other regions of the US were significantly more likely to
      have cutaneous cryptococcal disease (OR 3.8, 95% CI 1.1-14, P=0.045).
      CONCLUSIONS: Post-transplant cryptococcosis is more likely to present with
      cutaneous disease in the Southern region compared with other regions in the US.
      This predilection for cutaneous cryptococcosis could not be explained on the
      basis of differences in immunosuppression or the type of transplant. Whether our
      findings are related to strain-related variations in characteristics of the yeast
      or other transplant variables remains to be determined.

PMID- 21183882
TI  - Nineteen years of experience utilizing anti-T-Lymphocyte globulin induction in
      pediatric kidney transplantation.
AB  - BACKGROUND: The optimal immunosuppressive therapy in kidney transplantation
      remains controversial. Since 1990, we included, in our department, anti-T
      Lymphocyte globulin Fresenius(r) (ATG-F) in a sequential immunosuppressive
      therapy in pediatric recipients of deceased donor kidneys. We analysed
      retrospectively the complications and long-term outcomes. MATERIAL/METHODS:
      Ninety eight kidney transplants were performed in 91 children and adolescents
      between November 1990 and October 2009, using deceased donor source grafts. In
      86.8% of the recipients ATG-F was used as antibody induction and in 12.2% of the
      recipients no ATG-F induction was used. RESULTS: Overall graft survival rates at
      1, 5, 10 and 15 years were 91.8%, 86.1%, 75.9% and 61.9% respectively. In the ATG
      F group the graft survival at 1, 5, 10 and 15 years was 93%, 89.1%, 79%, 62.4%
      and in group without ATG-F it was 83.3%, 66.7%, 55.6% at 1, 5, 10 years
      respectively (p=0.27). The overall incidence of infection was 1.6/patient in the
      first year post-transplantation and almost all were of mild or moderate
      intensity. A papillary thyroid carcinoma was diagnosed in one patient and no
      lymphoid malignancies were observed during the observational period. All patients
      were alive at the end of follow-up, except one who died of cardiovascular
      disease, 7 months after graft loss. CONCLUSIONS: These results indicate that ATG
      F induction in pediatric kidney transplantation using deceased donor kidneys is
      associated with good graft and patient survival rates, and with low levels of
      complications.

PMID- 21183883
TI  - Artificial liver support: quo vadis?
AB  - BACKGROUND: Approximately 2 million persons worldwide die each year from hepatic
      failure. Because of the scarcity of donor organs, artificial liver support
      systems are being developed with the aim of either supporting patients with
      borderline functional liver cell mass until an appropriate organ becomes
      available for transplantation or until their livers recover from injury.
      MATERIAL/METHODS: A literature review was performed using MEDLINE, PubMed,
      EMBASE, and library searches. Only major liver support techniques are included in
      this review. RESULTS: A number of extracorporeal liver assist systems are in
      various stages of clinical development. Published data indicate that patients
      with acute and acute-on-chronic liver failure may benefit from treatment with
      some of these therapeutic measures. Results from large prospective randomized
      trials have shown that treatment with MARS(r) and PROMETHEUS(r) may not confer a
      survival advantage, despite positive effects on blood toxemia and improvement in
      hepatic encephalopathy. Currently, hemofiltration using albumin-leaking membranes
      is being explored as a novel promising approach to blood purification in liver
      failure. CONCLUSIONS: Developing an effective liver assist technology has proven
      difficult, because of the complexity of liver functions that must be replaced, as
      well as heterogeneity of the patient population. Non-biological systems may have
      a role in the treatment of specific forms of liver failure where the primary goal
      is to provide blood detoxification/purification. Biological systems appear to
      hold promise for treating liver failure where the primary objective is to provide
      whole liver functions which are impaired or lost.

PMID- 21183884
TI  - Significance of in situ hybridization results for EBV-encoded RNA in post
      transplantation lymphoproliferative disorder setting: report from the PTLD.Int
      Survey.
AB  - BACKGROUND: Epstein-Barr virus (EBV) encodes 2 small nonpolyadenylated noncoding
      RNAs termed EBERs. EBERs are the most common viral transcripts found in EBV
      infected cells. In the present study we aimed to examine various aspects of EBER
      positivity in PTLD patients. MATERIAL/METHODS: We conducted a comprehensive
      search for the available data by Pubmed and Google Scholar search engines for
      reports indicating results of EBERs in PTLD patients. Data from 27 previously
      published studies were included into analysis. Finally, 243 recipients of
      allograft were included into analysis. RESULTS: One and 5 years survival rates
      for PTLD patients with EBER-positive results were 61% and 50%, respectively,
      compared to 55% and 49%, respectively, for EBER-negative PTLD patients. When
      death specifically due to PTLD was used as the final outcome, EBER-positive PTLD
      patients had relatively superior outcome; although p-value did not reach the
      significance level (p=0.09). EBER-positive patients were significantly more
      likely to develop PTLD lesions of B cell types (vs. T cell type; p=0.018); and
      early onset PTLD (p<0.001). EBER-positive PTLD patients were significantly more
      likely to be polymorphic versus monomorphic (p=0.05). EBER-negative PTLD patients
      were more likely to develop non-Hodgkin PTLD lesions (p<0.001). CONCLUSIONS: We
      found that PTLD patients with positive results for EBER represent relatively
      better histopathological features than those in EBER-negative PTLD patients, and
      the survival rate of EBER-positive PTLD patients is not inferior to that of the
      EBER-negative subjects. Moreover, they were more likely to represent early onset
      PTLD of B cell type with polymorphic and Hodgkin-like lesions; and biopsy
      specimens from different organs were significantly different regarding EBER test
      results. Future studies with large PTLD populations are needed to confirm our
      findings.

PMID- 21183885
TI  - Heart transplantation in the elderly: why cardiac transplantation does not need
      to be limited to younger patients but can be safely performed in patients above
      65 years of age.
AB  - Within the last forty years, heart transplantation as the ultimate option for the
      treatment of end-stage heart disease has undergone dramatic changes and advances
      in operative techniques, postoperative care, immunosuppression, and rejection
      management which resulted in reduced morbidity and mortality. As the heart
      failure epidemic worsens and the population grows older, cardiac transplantation
      criteria have expanded for end-stage heart disease refractory to medical
      management. Although outcomes after cardiac transplantation have improved, the
      critical organ shortage is a limitation to its efficacy. The demand-supply
      disparity for heart transplantations has led to clinical and ethical issues
      examining adequate candidacy for organ transplantation. Cardiac transplantation
      in the elderly recipient was considered a contraindication due to poor survival
      rates compared to younger recipients. Given the increase in life expectancy over
      the last decades, single-center studies have assessed the outcome of
      transplantation among elderly recipients and comparable survival and quality of
      life have been described among older heart transplantation recipients.
      Alternatives to cardiac transplantation which have become more common, such as
      mechanical circulatory support, and further investigation of the viability of
      transplantation in the elderly may help determine the proper allocation of the
      limited organ supply.

PMID- 21183886
TI  - Prevention of flu episodes with colostrum and Bifivir compared with vaccination:
      an epidemiological, registry study.
AB  - The aim of this study was to evaluate the efficacy of colostrum (ARD Colostrum)
      in association with the immunomodulator Bifivir in the prevention of flu episodes
      compared with anti-flu vaccination. The registry groups included no prevention,
      vaccination, vaccination+immunomodulators, and immunomodulators only. Groups were
      comparable for age and sex distribution. In the group without prevention there
      were 8 major episodes and 12 minor episodes out of 34 subjects (8-12/34); in the
      vaccination group the respective figures were 8-13/38; in the group treated with
      a combination of vaccination and immunomodulators (ARD Colostrum + Bifivir) the
      figures were 4-9/33; and in the group treated with immunomodulators only there
      were 11 viral episodes (3-8) in 36 subjects. The episodes in the
      vaccination+immunomodulators and immunomodulators only groups were significantly
      lower compared with the other two groups (P<0.05). The number of episodes
      registered with the immunnomodulators was significantly lower than those observed
      in patients using vaccination or no prevention (P<0.05). The number of days of
      disease was higher in untreated controls compared to the groups treated with
      immunomodulators (P<0.05) and 2 times higher in the vaccination group compared to
      the same groups (P<0.05). The average relative costs were significantly lower
      (2.3 times) in the immunomodulators groups in comparison with the other groups
      (P<0.05). No problems concerning tolerability or side effects were observed
      during the study. Compliance was very good. In conclusion, the administration of
      immunomodulators is very cost effective and appears to be more effective than
      vaccination to prevent flu.

PMID- 21183887
TI  - Prevalence of depression in patients affected by subclinical hypothyroidism.
AB  - AIM: The aim of this study was to estimate the prevalence of depressive symptoms
      in patients affected by subclinical hypothyroidism by means of Hamilton Rating
      Scale for Depression (HAM-D) and Montgomery-Asberg Depression Rating Scale
      (MADRS); to assess which depressive symptoms are prevalent in our population,
      with references to the factorialization of HAM-D by Cleary and Guy (1977); to
      verify whether levothyroxine replacement therapy alone can induce total remission
      of depressive symptoms. METHODS: The study enrolled 63 patients affected by
      subclinical hypothyroidism undergoing follow-up at the endocrinology service of
      San Paolo Hospital in Milan. All patients underwent an evaluation by means of HAM
      D and MADRS scales and serum TSH, free T4, free T3, TPO-Ab and Tg-Ab levels were
      measured. RESULTS: We estimated a prevalence of depressive symptoms in our
      population of 63.5%. Concerning the qualitative assessment of psychiatric
      disturbances in the population we considered, our results showed that the most
      frequent symptoms were part of four factors, according to the Cleary and Guy
      factorialization of HAM-D: these factors are representative of anxiety and
      somatisation (factor I), cognitive impairment disturbances (factor III),
      psychomotor retardation (factor V) and sleep disorders (factor VI). Levothyroxine
      replacement therapy alone wasn't effective in inducing total remission of
      depressive symptoms. CONCLUSION: This study suggests the importance of a
      psychiatric evaluation in patients affected by subclinical hypothyroidism.

PMID- 21183888
TI  - Relation of C. pneumoniae antibodies to inflammation and atherosclerosclerosis in
      dialysis patients.
AB  - AIM: the aim of this study was to investigate the association between the
      presence of antibodies to C. pneumoniae, some markers of inflammation and the
      presence of preclinical atherosclerotic lesions in hemodyalisis (HD) patients
      treated with different dialytic membranes. METHODS: C. pneumoniae antibodies were
      measured by microimmunofluorescence in blood samples of 68 chronic HD patients
      and in 120 healthy blood donors. Intima-media thickness (IMT) of carotid and of
      femoral arteries, eco-color doppler of sovraortic trunk and lower limb vessels
      were evaluated. Plasma levels of C-reactive protein (CRP) and terminal complement
      (C) complex, C5b-9, were measured. RESULTS: HD patients treated by cellulosic
      membranes have significantly higher plasma levels of C5b-9 and of CRP compared to
      those treated by synthetic membranes. A significantly higher prevalence of IgG
      antibodies to C. pneumoniae and also at higher titre was observed in HD patients
      in comparison to the controls (66% vs. 28%). The carotid artery mean wall
      thickness was significantly lower in C. pneumoniae seronegative patients than C.
      pneumoniae seropositive patients. Similar results were obtained for limb
      arteries. The use of cellulosic membranes, but not synthetic membranes, was
      associated with higher carotid IMT and this was independent of the C. pneumoniae
      serology status. CONCLUSION: in addition to known risk factors, the type of
      dialytic membrane used may contribute to the progression of atherosclerosis
      lesions in HD patients. Our data strengthen the evidences that C. pneumoniae
      infection under high inflammatory status might be a further risk factor for
      progression of atherosclerosis in HD patients, particularly in those treated with
      cellulosic membranes.

PMID- 21183889
TI  - Immunotolerance reaction for allograft-limb in rats induced by gene-modified cell
      transfusion.
AB  - The therapeutic value of the transforming growth factor beta 1 (TGF-b) in
      transplantation has been reported; However, cell-mediated gene therapy using TGF
      b is not applied to the organ transplantation widely. This study was to evaluate
      whether TGF-b-modified donor spleen cell specific transfusion in rat heterotopic
      allo-limb transplantation could induce tolerance tolerogenicity and prolong
      allograft's survival time. The Splenic T-cell in Wistar rats responsing to donor
      spleen cells which received TGF-b-transduced were severely impaired.The Survival
      time of Sprague-Dawley Allograft-limb in Wistar rats given TGF-b-modified donor
      spleen cells (5Y106 cells/well, administration of donor TGF-b-transduced donor
      spleen cells 7 days before transplantation) was extended modestly but
      significantly.

PMID- 21183890
TI  - Imaging and focal therapy in prostate and kidney cancer.
AB  - The advancement of imaging modalities in the past two decades has led to the
      increased incidence of small renal masses. This same technology is making nephron
      sparing treatment of small renal masses much more feasible and precise. The goal
      of this manuscript is to review the currently available imaging modalities
      utilized in focal treatment and follow-up of small renal masses.

PMID- 21183891
TI  - Current role and future perspective of MRI for diagnosis and characterization of
      renal cell carcinoma.
AB  - During the past years, magnetic resonance imaging (MRI) has been established as a
      reliable method for examination of the kidneys. Modern MRI systems enable to
      visualize renal masses with a high spatial resolution. This enables not only to
      differentiate between benign lesions and renal cancer but also to define the
      tumor stage with high accuracy. The impact of a precise preoperative staging has
      increased significantly due to stage adapted therapy approaches such as nephron
      sparing surgery or local ablative techniques (e.g. radiofrequency ablation).
      Tumor-related infiltration of the renal pelvis, infiltration of the perinephric
      fat or a tumor thrombus within the inferior caval vein has to be diagnosed with
      high accuracy to enable these stage adapted treatment regimens. This article
      introduces into clinically established "morphologic" MRI techniques for diagnosis
      and staging of renal cell carcinoma (RCC). Besides detection and staging of
      kidney cancer, the recent development of molecularly targeted therapies in
      patients with metastatic or non-operable tumors has led to novel diagnostic
      demands. To evaluate treatment efficiency, more information than just tumor
      morphology should be provided. Functional imaging techniques including dynamic
      contrast enhanced (DCE) MRI, diffusion weighted imaging (DWI), arterial spin
      labeling (ASL) and MR-spectroscopy are being investigated in preclinical and
      clinical trials. While some new techniques have shown promising results for a
      broad clinical application, others seem to be suited for dedicated questions
      only.

PMID- 21183892
TI  - The safety and oncologic efficacy of radio-frequency ablation for the treatment
      of small renal masses: comprehensive review of the current literature.
AB  - The success of radio frequency ablation (RFA) into various surgical fields has
      fueled the interest of the urological community to study its application in small
      renal masses (SRM). However, some controversies remain regarding its oncologic
      efficacy. This paper reviews the effects of technical factors and tumor/tissue
      characteristics on treatment success, discuss the evaluation of treatment success
      by post-treatment imaging and histopathology, and highlight intermediate term
      oncologic outcomes of recent, larger RFA series. The authors have performed a
      Medline database search regarding the treatment of SRM by RFA from 2003 through
      August 2010. To evaluate technical factors and tissue characteristics influencing
      treatment success, and the evaluation of treatment success by imaging and
      histopathology, papers were selected when they provided detailed descriptions on
      one or more of these items. For the analysis of oncologic outcomes, the selection
      was limited to series that treated a minimum of 20 patients or a minimum follow
      up of 48 months and reported effectiveness based on follow-up imaging. Technical
      evolutions and correct patient/tumor selection produced increasingly higher
      success rates with RFA. Even though tumor skipping has been described in
      preclinical studies and early clinical trials, this does not seem to influence
      efficacy of the procedure. Indeed, a 8.7% retreatment rate exists. However,
      accepting this potential downside, final ablative success rate is 94.1% at
      intermediate term follow-up. Complications after RFA are less frequent and more
      often minor compared to surgical series. The present analysis reveals that RFA
      achieves a high intermediate-term ablative success rate when accepting an 8.7% re
      ablation rate. Complication rates are low and usually minor. Based on this data,
      RFA represents an attractive minimal invasive treatment for SRM, especially in
      the growing elderly patient population with multiple comorbidities. Long-term
      follow-up data are expected to confirm the role of RFA in the treatment of SRM.

PMID- 21183893
TI  - Laparoscopic and percutaneous cryotherapy for renal neoplasms.
AB  - Incidence of renal cell carcinoma is increasing. There has been a shift towards
      utilization of nephron sparing surgery when feasible. Minimally invasive ablative
      treatments such as laparoscopic and percutaneous renal cryoablation aim to treat
      renal tumors with the two goals of cancer eradication and reduced morbidity
      compared to excisional surgical approaches. In this article, we review the basis
      of cryobiology and examine the current role of renal cryoablation and analyze the
      current literature focusing on laparoscopic and percutaneous approaches and
      discuss future directions and refinements in cryosurgical technology. While renal
      cryoablation is associated with higher local retreatment rates compared to
      radical or partial nephrectomy, emerging reports of intermediate-term oncological
      outcomes suggest disease-specific survival approaching that of extirpative
      surgery. Further follow up is needed to elucidate the long-term oncologic
      outcomes of and effects on renal function by renal cryoablation.

PMID- 21183894
TI  - Glucocorticoid induced risk of fractures.
AB  - In recent years studies have emphasized the importance of glucocorticoid-induced
      osteoporosis as the second most common form of osteoporosis after postmenopausal
      osteoporosis. Several studies have underlined that glucocorticoids are
      responsible for decreasing bone mineral density and increasing bone fragility,
      resulting in a large increase in fracture risk. This review wants to provide a
      background regarding the fracture risk of patients exposed to glucocorticoid
      treatment, considering the fracture risk as the most appropriate parameter to
      valuate glucocorticoid-induced osteoporosis. In fact, glucocorticoid treatment
      induces bone loss and increases fracture risk above all affecting trabecular
      bone, probably through an alteration in bone turnover and microarchitectural
      changes responsible for an early increased fracture risk which is primary
      influenced by dose and duration of treatment, body mass index, age and female
      gender.

PMID- 21183895
TI  - Etiopathogenetic advances and management of holoprosencephaly: from bench to
      bedside.
AB  - Holoprosencephaly (HPE) is a complex brain malformation caused by impaired or
      incomplete midline division of the prosencephalon. It's characterized by cerebral
      and facial anomalies of different levels of severity. Both genetic and
      environmental factors are known to cause HPE, but they cover only few cases.
      Genetic causes are responsible for about 20% of cases: they are chromosomal
      abnormalities and gene mutations: up to date, nine genes (SHH, ZIC2, SIX3, TGIF,
      PATCHED1, TDGF1/CRIPTO, FAST1, GLI2 and DHCR) are definitely associated with HPE,
      but many others candidate gene are under investigation. The diagnosis of HPE is
      usually prenatal and is based on systematic ultrasound scan (US) and magnetic
      resonance imaging (MRI). Children with HPE have many medical problems in
      agreement with the severity of the brain malformation: craniofacial
      abnormalities, neurological signs, endocrine disorders, oromotor and dysautonomic
      dysfunction, thus requiring a multidisciplinary team for symptomatic treatment of
      manifestations, prevention of complications and parental support. Genetic
      counselling is an important step, often made difficult by extreme phenotypic
      variability, genetic heterogeneity, and a high risk of recurrence in apparently
      sporadic cases. In conclusion it can be concluded that we are far from a complete
      explanation of the etiopathogenesis. Future researches on genomic rearrangements
      all over the genome with techniques like the CGH array should lead to the
      identification of other causal genes and could improve diagnosis and prognosis. A
      skill multidisciplinary approach is mandatory to offer the better clinical
      assistance to patients and their parents.

PMID- 21183896
TI  - CT onset of influenza A (H1N1) complicated with severe pneumonia in two typical
      cases.
AB  - The novel influenza A (H1N1) virus developed in the United States and Mexico in
      April 2009 and has spread worldwide rapidly. Pulmonary complications are major
      reason of death associated with influenza A (H1N1) infection. Thus, it is
      necessary to investigate characteristics on the turnover of A (H1N1) infection
      complicated with pneumonia. Although the chest radiographic findings of the
      influenza A (H1N1) pneumonia were described in a clinical report, the CT findings
      involving turnover of influenza A (H1N1) complicated with severe pneumonia have
      not yet been reported. We report two typical cases of novel influenza A (H1N1)
      pneumonia with chest CT findings and investigate features and turnover of
      influenza A(H1N1) pneumonia. From the CT appearance of two cases, we found that
      influenza A(H1N1) complicated with pneumonia might progress rapidly, but it would
      recover in two or three weeks once it was controlled effectively. The CT images
      in our report might help the clinician to clearly understand the patterns of
      onset, progression and outcomes in influenza A(H1N1) complicated with pneumonia.

PMID- 21183897
TI  - Efficacy of amoxycillin plus clavulanic acid-based triple therapy for
      Helicobacter pylori eradication: a retrospective study.

PMID- 21183899
TI  - [Memory disorders in multiple sclerosis].
AB  - Disturbances of short-term memory are the most early and frequent alterations of
      cognitive functions in multiple sclerosis (MS). We have conducted a complex
      neuropsychological and brain MRI study in patients with MS. The disturbances of
      memory were found in MS patients regardless of disease type and duration. The
      central pathophysiological process of the development of cognitive disturbances
      in MS is the lesion of projection, commissural and long association fibers that
      results in the disturbances of integrative brain activity and activation of the
      cortex in deep structures, first of all, in the thalamus.

PMID- 21183898
TI  - Riedel's thyroiditis and cerebral venous sinuses thrombosis: a case report.

PMID- 21183900
TI  - [Clinical predictors of the therapeutic response to valdoxan in moderate and
      severe depression].
AB  - Authors have analyzed the efficacy of valdoxan in treatment of moderate and
      severe depression from the position of clinical predictive factors for the most
      full drug response leading to the remission. A number of patients was 50,
      duration of therapy was 6 weeks. Due to the recurrent course and a severe
      depressive episode, the dosage was 50 mg per day from the second week of
      treatment in most patients (97,5%). Ten patients (20%) were withdrawn from the
      study. Among patients completed the study, 36 (90%) were considered responders.
      The most pronounced response leading to the remission was seen in 27 patients.
      Significantly lower frequency of anxiety depression, night insomnia represented
      by one of the variants, presence of atypical daily rhythm, as a rule, in the form
      of worsening in the evening hours, significantly higher frequency of symptoms
      referred to "Muscle tension" in the structure of generalized anxiety disorder
      (DSM-IV), persistent or periodic autonomous disorders regardless of the reactive
      lability or nonsignificant physical tension were specified as clinical predictors
      for the full response to the drug leading to the remission. Among comorbid
      disorders, the predictors were paroxysmal anxiety with-or without agoraphobia.

PMID- 21183901
TI  - [Hand motor dysfunctions in computer users].
AB  - It were studied 239 female typists aged from 16 to 62 years (mean age 20,1+/-7,8
      years) using author's questionnaire for computer typists to assess hand function
      and develop preventive measures of disturbances revealed. Indirect signs of
      tunnel hand neuropathy (27,2%), focal hand dystonia (21,4%) and muscular-tonic
      syndromes of different localization (18%) have been found. Typists are a risk
      group of fine hand motor dysfunctions. As preventive measures, authors recommend
      to use computer auxiliary devices, to change a motor stereotype during the day,
      to make hand "motor holidays", to organize working place.

PMID- 21183902
TI  - [Clinical features of headache of tension type and principles of treatment].
AB  - We examined 140 patients, aged from 23 to 47 years, with headache of tension type
      (HAT). Patients were stratified into two groups: HAT with trigger zones in
      pericranial muscles (HAT-1) and HAT without those (HAT-2). The study included the
      detection of pain threshold and pain tolerability in pericranial muscles using
      pressure algometer, quantitative assessment with the McGill Pain Questionnaire,
      evaluation of depression and anxiety. Loci of primary and secondary hyperalgesia,
      signs of anxiety disorder were observed in patients with HAT-1. Diclofenac sodium
      had a temporary effect and tizanidine had a stable positive effect. In patients
      with HAT-2, we found loci with signs of secondary hyperalgesia in pericranial
      muscles and symptoms of depression. There was no effect of diclofenac sodium,
      tizanidine had a subtle positive effect and venlafaxine exerted a good stable
      effect. In conclusion, there are different pathophysiological mechanisms of HAT
      with the presence of trigger zones in pericranial muscles and HAT without trigger
      zones.

PMID- 21183904
TI  - [Efficacy of vinpotropile in the therapy of initial signs of cerebrovascular
      pathology].
AB  - We conducted an open study on efficacy and safety of vinpotropile in patients
      with initial signs of chronic brain ischemia. Twenty patients, aged from 50 to 78
      years, were examined. Seven patients had the diagnosis of discirculatory
      encephalopathy (DE), I stage, and 13 patients were diagnosed with DE, II stage.
      Vinpotropile was prescribed in 2 capsules tree times per day during 30 days. At
      the end of the study (the 30th day), the results of the therapy were assessed as
      very good or good in 75% of patients. Also, positive changes were seen in the
      performance on neuropsychological tests: MMSE scores were improved in average by
      1,9 point, the mean score in the group being corresponded to normal values.
      Patients performed better on the Isaac speech activity test. The higher
      performance on the task and less errors were seen in the proof test that
      reflected the increase of attention/concentration. Patients showed the
      significant improvement on a scale that assessed self-rated health, activity and
      mood. The emotional state was normalized in 50% of patients during the treatment
      with vinpotropile. No adverse effects were observed.

PMID- 21183903
TI  - [New approaches to the treatment of chronic daily headache].
AB  - Two groups of patients with chronic daily headache have been treated: 16 patients
      of the first group received katadolon (flupirtin) in dose 300 mg per day during 2
      months as an alternative analgesics instead of combined sedative drugs (sedalgin,
      pentalgin, citramon) that patients abused for many years. The withdrawal period
      was painless, the use of katadolon resulted in the reduction of attack frequency
      and the decrease in the amount of traditional analgesics. Katadolon was well
      tolerated, only two patients reported the total weakness and 1 patient reported
      diarrhea. Velafax (venlafaxine) in dose 75 mg per day was prescribed to 18
      patients of the 2nd group during 6 weeks. The treatment resulted in the decrease
      of attack frequency and pain intensity. Velafax reduced allodynia which was
      studied using algometria and touches, and wind-up phenomenon. There was the
      significant increase of the R3 component of nociceptive blink reflex threshold
      and pain threshold of nociceptive flexor reflex that indicates the augmentation
      of antinociceptive protection and decrease in the sensitization of central
      nociceptive neurons of the trigeminal nerve. Patients treated with Velafax
      experienced nausea, constipation, impairment of sustained attention, decrease of
      appetite however these side-effects were mild and passed without treatment during
      5-7 days.

PMID- 21183905
TI  - [Treatment of depression after stopping acute psychosis in patients with
      schizophrenia].
AB  - The aim was to study the efficacy of different groups of neuroleptics and
      antidepressants in the treatment of depression after stopping acute psychosis in
      schizophrenic patients. Authors observed 183 patients during the treatment using
      a psychopathological method and a battery of psychometric scales for assessing
      patient's state, structure of psychopathological syndrome and side-effects of the
      drugs. Correlation analysis was applied to compare treatment characteristics with
      the dynamics of disease course (favorable or less favorable) during 8 years. We
      used 13 antipsychotic drugs, including depot drugs, and 15 antidepressants. In
      conclusion, the additional and strictly differentiated prescription of
      antidepressants in the treatment of schizophrenic patients with depressive
      symptoms after stopping acute psychosis is effective and safe. It allows to
      improve quality of life and prognosis of patients.

PMID- 21183906
TI  - [Hemodynamic and biochemical characteristics of the prefrontal cortex after the
      first episode of juvenile schizophrenia].
AB  - Authors analyzed biochemical (data obtained by proton MR spectroscopy) and
      hemodynamic ( data of fMRI) characteristics of the prefrontal cortex in 7
      patients with juvenile shift-like schizophrenia examined during remission after
      the first episode and in 8 mentally healthy subjects matched for sex and age. The
      between-group differences in the tested parameters were not found, however, the
      neurobiological features of the prefrontal cortex were correlated with the
      psychopathological symptoms assessed with the PANSS.

PMID- 21183907
TI  - [The use of antistax in the treatment of discirculatory encephalopathy].
AB  - Authors have studied the effect of antistax on the cerebral venous discirculation
      (VD) in patients with discirculatory encephalopathy. Forty-three patients (mean
      age 46,8+/-1,8 years) received antistax in daily dose 720 mg during 2 months.
      Efficacy of treatment was assessed using the Visual Analogous Scale, Doppler
      ultrasound data, result of a non-invasive study of peripheral arterial tonus
      (PAT). After the completion of treatment course, the significant decrease of
      complaints, intensity of VD by the ultrasound data and parameters of arterial
      hardness by PAT data was observed. The excellent tolerability was reported by
      61,1% patients; good one - by 38,9%. The results confirm the possibility of using
      antistax in neurological practice for treatment cerebral VD.

PMID- 21183908
TI  - [Cognitive functions in patients with idiopathic generalized and cryptogenic
      focal epilepsy].
AB  - The study included 32 patients with idiopathic generalized epilepsy, 20 patients
      with cryptogenic focal epilepsy and 20 healthy controls. Cognitive functions were
      assessed using tests of long- and short-term verbal memory (auditory, visual and
      motor), attention and word fluency. Correlations between clinical features of the
      epileptic process and cognitive deficit were analyzed. Cognitive functions in
      patients with epilepsy were significantly lower compared to controls. Long-term
      auditory verbal memory and attention were significantly worse in patients with
      cryptogenic focal epilepsy compared to those with idiopathic generalized
      epilepsy. The cognitive dysfunction was correlated with seizure frequency,
      disease duration, lifetime number of seizures, in particular generalized tonic
      clonic seizures.

PMID- 21183909
TI  - [Specialties of prolactin secretion and peripheral reproductive sex hormones in
      patients with of first episode of schizophrenia].
AB  - Levels of prolactin, estradiol and testosterone have been assessed in 50 first
      episode drug naive patients with schizophrenia (23 women and 27 men) and 17
      mentally healthy people. All patients have been stratified into two groups by sex
      and into two subgroups by severity of psychopathological symptoms. The levels of
      prolactin and estradiol were higher in men compared to the control group. In
      women, the level of estradiol was lower and the level of testosterone was higher
      regardless of burden of psychopathologic symptoms. The decrease of testosterone
      level was found in males with acute psychopathologic symptoms. The increase of
      psychopathologic symptoms leads to lowering of prolactin level regardless of sex
      that confirms the dopamine theory of schizophrenia. The results of this study
      confirm the protective role of estrogen in the development of disease.

PMID- 21183910
TI  - [Efficacy of cytoflavin in the treatment of burns patients with toxic and post
      hypoxic encephalopathy].
AB  - The thermal injury leads to increasing level of intracellular reactive oxygen
      specimen (ROS) reducing the antioxidant defense system. This pathway has been
      associated with endothelial and microvascular dysfunction and finally with
      multiple organ dysfunction (MOD). The purpose of this prospective, randomized
      clinical study was to determine the oxidant-antioxidant balance and investigate
      the effects of antioxidant therapy (cytoflavin) in burns patients with toxic and
      post-hypoxic encephalopathy. The study included 60 patients with thermal trauma
      and encephalopathy. Thirty patients received standard intensive therapy and
      cytoflavin intravenously in dose 10 ml/day 24 h after trauma during 5 days and 30
      patients of the control group received standard intensive therapy for burns. Both
      groups exhibited a high lipid peroxydation (LPO) (malondialdehyde, conjugate
      trienes) and low levels of the antioxidant defense system, vitamins A and E on
      the second day after trauma. On the 14th day of treatment, the level of LPO
      (p<0,01) and total MOD (p<0,05) index were significantly lower and MMSE scores
      were higher (p<0,01) compared to the control group. In conclusion, cytoflavin,
      due to its systemic and metabolic effects, was effective in the treatment of post
      hypoxic encephalopathy after the thermal injury.

PMID- 21183911
TI  - [Clinical and neurophysiological study of the efficacy of adaptol in the
      treatment of emotional burn-out].
AB  - The study aimed at therapeutic effect of adaptol on burn-out syndrome. Authors
      examined 32 patients aged from 25 to 45 years. Adaptol was prescribed in day dose
      1500 mg during 60 days. Clinical, psychological and electroencephalographic study
      (EEG) was conducted before and after the treatment course. The data of adaptol
      positive influence on the basic clinical symptoms (reduction of asthenic and
      anxiety scores) is obtained. The analysis of EEG results allows to draw
      conclusions on normalisation of brain functional activity after therapy.

PMID- 21183912
TI  - [Pantogam in the treatment of patients with organic brain lesions of different
      genesis].
AB  - We studied 35 patients with organic brain lesions caused by secondary brain
      harmful factors (group 1) and 33 patients with organic brain diseases of vascular
      genesis (group 2). Mean age of patients was 45.5+/-2.3 years. Asthenic,
      cerebroasthenic, psychoorganic syndromes in the combination with dissomnic,
      psychoautonomous, depressive, hypochondriac disorders predominated in the
      clinical picture of patients. Pantoham was prescribed in dose 1.0 g 3 times daily
      during 45 days. The effect of the drug on cognitive and mental disorders was
      found. The drug was most effective in patients of group 1. Pantoham was well
      tolerated.

PMID- 21183913
TI  - [Receptor system of brain vessels in arterial hypertension].
AB  - We conducted a post-mortem study of the receptor system of brain vessels in
      patients with arterial hypertension (AG), stages I-III, and healthy people using
      impregnation and a method of measuring NADPH-diaphorase. The receptor system of
      arterial wall is represented by treelike and glomerular structures with moderate
      enzyme activity. Reactive and destructive disturbances of the receptor system
      that were distinctly seen on histochemical preparations were found in brain
      arteries of AG patients. The intensity of changes in the nervous apparatus of
      brain vessels was closely related to the artery caliber, their localization,
      disease duration and severity, with the most early and deep changes in the
      afferent fibers and receptors of the pia mater arteries. In intracerebral
      arteries, reactive changes in receptor structures were found in long-term
      hypertension and destructive changes were found in AG, stages II-III.

PMID- 21183914
TI  - [Molecular-genetic approach to the clinical and nosologic differentiation of
      schizoaffective disorder].
AB  - The aim of the study was to find molecular-genetic variants associated with
      nosologically independent schizoaffective disorder (SAD) which clinical
      presentations had been specified earlier. Authors studied a sample of 230
      patients including 39 with "nuclear" (nosologically independent) and marginal
      (intermediate) variants of SAD, 53 with schizophrenia with schizoaffective states
      and 81 with schizophrenia with affective disorders in the structure of psychotic
      attacks. In these groups, authors studied the following polymorphisms: 5-HTTLPR,
      Val66Met BDNF, T102C 5-HTR2a and S677T MTHFR. Frequencies of genotypes were
      compared to those in a sample of healthy controls (328 people). It has been shown
      that the "nuclear" variant has a genetic profile represented by a combination of
      genetic variants (SS*ValVal*TT*CC) that distinguishes this clinical entity from
      other groups and controls. The results may be used as an additional criteria for
      clinical and nosological differentiation of SAD from schizophrenia.

PMID- 21183915
TI  - [Gender features of low back pain syndromes].
AB  - Forty-four patients with low back pain caused by a radix syndrome (mean age
      46.18+/-9.11 years) have been examined. Patients have been stratified by sex. The
      pain syndrome has been assessed in 1st, 10th and 21st by the VAS, pressure pain
      measurement and laboratory tests for measuring neurotransmitter levels. It has
      been shown that women endure a pain worse as assessed not only by the
      questionnaires but also by the pressure pain measurement especially at night. The
      analysis of blood serum revealed higher levels of beta-endorphin, serotonin,
      dopamine that were correlated (r<0.05) with the pain level, their amount
      decreasing with the reduction of pain.

PMID- 21183916
TI  - [Vinpotropil in the treatment of dyscirculatory encephalopathy with cognitive
      impairment without dementia].
AB  - The fixed combination containing 5 mg of vinpocetine and 400 mg of pyracetam
      (vinpotropil) was prescribed to 349 patients with dyscirculatory encephalopathy,
      I-II stages in dose one capsule three times a day during 3 months. After this
      treatment, repeated neuropsychological testing showed significant diminishing of
      dysexecutive cognitive impairment linked with frontal lobes dysfunction. The
      cognitive improvement was associated with the regress of subjective neurological
      symptoms like headache, dizziness, tinnitus, fatigue and insomnia. Vinpotropil
      was safe and well tolerated in elderly patients with chronic cerebral vascular
      insufficiency.

PMID- 21183917
TI  - [Omaron in the complex treatment of patients with multiple sclerosis].
AB  - We studied efficacy and tolerability of the combined drug omaron (25 mg of
      cinnarizine and 400 mg of piracetam in one tablet) in patients with multiple
      sclerosis. The dosage of the drug was 1 tablet 3 times a day during 12 weeks in
      33 patients (mean age 35.3+/-4.2 years) of the index group. A comparison group
      consisted of 27 patients matched for demographic and clinical characteristics who
      did not receive nootropics during the study. None of patients included in the
      study received disease modifying drugs. The significant (p<0.05) decrease in the
      severity of chronic fatigue syndrome (by 28.6% compared to baseline), improvement
      (p<0.05) of cognitive functions (increase of MMSE scores by 9.4%) were found in
      the index group compared to the comparison one. The statistically significant
      changes in the severity of disability assessed by EDSS were not observed. Omaron
      was well-tolerated with no serious adverse-effects.

PMID- 21183918
TI  - [Pharmacotherapy of motor manifestations in late stages of Parkinson's disease].
AB  - Accumulating data on experience of long therapy with levodopa revealed the
      pathomorphosis of clinical presentations of Parkinson's disease during its
      progression, in particular, described, the occurrence of motor fluctuations and
      levodopa-induced dyskinesias. In later stages of the illness, these disturbances
      attracted special attention of both the patient, and the attending, worsening
      quality of a life of patients. The article describes the main issues of the
      pathogenesis of this type of disorders and the currently available strategies for
      its treatment. We present our own experience of treatment motor fluctuations by
      means of the combined three-component medical product stalevo containing
      levodopa, carbidopa and entacapone.

PMID- 21183919
TI  - [Asthenic disorders in children].
AB  - The present study comprised two parts. In the first part, authors attempted to
      work out the systematics of asthenic disorders based on our own observations of
      189 children aged 7-14 years. The following clinical variants of asthenic states
      in children were singled out: cerebrogenic asthenia (14.3%), somatogenic (13.8%),
      residual (16.4%), dysontogenetic (20.1%) and neurasthenia (35.4%). In the second
      part, we summarized the results of treatment of neurasthenia with adaptol (32
      patients) compared to pantoham (30 patients). The efficacy of adaptol was higher:
      the improvement was seen in 71.9% of cases compared to pantoham (56.7%). The good
      tolerability of adaptol which clinical efficacy is confirmed by
      neurophysiological and psychological studies is discussed.

PMID- 21183920
TI  - [Treatment of patients with moderate and severe nonpsychotic depressions].
AB  - Twenty-three patients with moderate and severe nonpsychotic depressions without
      psychotic symptoms were treated with valdoxan during 8 weeks. Valdoxan was used
      in the combination with antidepressants and tranquilizers in 73.9% patients, the
      latter drugs were withdrawn after 3-6 weeks in 65.3% of cases. The distinct
      positive changes in the mental state of patients were seen on CGI-I and HADM-21
      scales. To the end of the study, 69.6% of patients were practically healthy
      according to the CGI-S scale; 17.4% had border-line psychiatric disorder without
      symptoms of depression; 13% had mild depressive symptoms. No significant side
      effects were observed in 91.3% of patients.

PMID- 21183921
TI  - [Methods of statistical analysis in psychiatric publications].
AB  - In order to evaluate the use of statistical methods, authors analyzed the
      articles in the "Korsakoff Journal of Neurology and Psychiatry" 2007-2008 (351
      articles) and the "Social and Clinical Psychiatry" 2007 (73 articles). The data
      were compared to the results of the similar Russian study performed 15 and 20
      years ago and the English-language study performed 25 years ago. It has been
      concluded that the share of articles without any statistical data analysis has
      decreased dramatically, the use of tables and graphs has become obligatory, t
      test has become one of the most used (without any explication of its usage in
      many cases). Russian publications remain behind English-language articles in
      using statistical methods.

PMID- 21183922
TI  - [Anti-acetylcholine receptor antibodies: effect of immunosuppressive drug therapy
      in patients with myasthenia gravis].
AB  - We studied anti-acetylcholine receptor antibodies (ARAb) in 25 patients with
      myasthenia gravis before and after the immunosuppressive drug (steroid) therapy
      and in 22 patients before and after thymectomy. The clinical effect after the
      treatment was correlated with the reduction of ARAb levels by more than 20% in
      62% of patients. The ARAb levels did not change, or even increased, in 15%
      patients despite the improvement of their clinical state. We showed the direct
      correlation between the clinical improvement and the decrease of ARAb level.

PMID- 21183923
TI  - [Changes of functional activity of peripheral blood leukocytes during the
      immunotherapy of tick-borne infections in children].
AB  - We studied the peculiarities of functional activity of peripheral blood
      leukocytes in different etiological variants and clinical forms of tick-borne
      infections in 629 children aged from 1 to 14 years. The decrease of biocide
      potential of neutrophils was accompanied by most severe clinical manifestations.
      The analysis of changes in defensin levels in different clinical forms of tick
      borne infections revealed the most significant changes in cases of mixed
      infection. The dynamics of functional activity of leukocytes during the
      cycloferon immunotherapy reflected the effectiveness of recovering process in
      biocide potential regardless of the infection etiology. The main advantage of
      immunotherapy is the possibility of its use in the complex treatment before the
      serologic confirmation of the diagnosis regardless of disease etiology.

PMID- 21183924
TI  - Migraine and preterm birth.
AB  - OBJECTIVE: To investigate whether maternal migraine was associated with preterm
      birth. STUDY DESIGN: Case-control sample within a population-based study of risk
      factors for cerebral palsy (CP). Infants without CP were matched for gestational
      age with those with CP. Maternal migraine was self-identified at first prenatal
      visit, most in the first trimester. RESULT: Infants without CP born to women with
      migraine had a higher rate of preterm birth (odds ratio (OR)=3.5, 95% confidence
      interval (CI) 1.5, 8.5), as did infants who died in the perinatal period (OR=7.3,
      95% CI 0.98, 54), the difference marginal for nominal statistical significance.
      In all outcome groups, infants of women with migraine had a higher observed rate
      of suboptimal intrauterine growth. In term infants, the rate of maternal migraine
      was higher in those with CP than in controls (OR=2.18, 95% CI 0.92, 5.25). Pre
      eclampsia was reported more frequently in women with migraine who gave birth to a
      child with CP or a perinatal death, particularly in those born preterm; OR=5.1
      (1.3, 20) and OR=2.9 (1.1, 7.6), respectively, but not in women giving birth to a
      control whether term or preterm. CONCLUSION: Maternal migraine, as self-reported
      early in pregnancy, was associated with preterm birth in survivors without CP and
      in infants who died in the perinatal period. The combination of maternal migraine
      and pre-eclampsia was associated with CP and perinatal death. The association of
      maternal migraine with outcomes of pregnancy warrants further study.

PMID- 21183925
TI  - Follow-up cervical length in asymptomatic high-risk women and the risk of
      spontaneous preterm birth.
AB  - OBJECTIVE: To determine whether further cervical length shortening by
      transvaginal ultrasonography in asymptomatic high-risk women with a short
      cervical length adds additional predictive value for spontaneous preterm birth
      and perinatal morbidity. STUDY DESIGN: Women with a history of spontaneous
      preterm birth, loop electrosurgical excision procedure, cone biopsy or uterine
      anomaly, who were pregnant with singleton gestations and were found by
      transvaginal ultrasonography to have a cervical length <3.0 cm at 20 to 28 weeks'
      gestation, and who underwent a follow-up cervical length within 3 weeks were
      evaluated, comparing those with further cervical length shortening (>10%) to
      those without further shortening. Primary outcomes were spontaneous preterm birth
      <35 weeks' gestation and perinatal morbidity. Secondary outcomes included
      spontaneous preterm birth <37 weeks, <34 weeks, <32 weeks, birth weight <2500 g,
      maternal and other neonatal outcomes. RESULT: Compared with women without further
      cervical shortening, those with further shortening were found by univariate
      analyses to have higher rates of spontaneous preterm birth <35 weeks (34.8 versus
      8.5%, P = 0.014), <37 weeks (56.5 versus 21.3%, P = 0.003), <34 weeks (30.4
      versus 2.1%, P = 0.001), <32 weeks (21.7 versus 0%, P = 0.003), birth weight
      <2500 g (60.9 versus 17.0%, P<0.0001), neonatal intensive care unit admission
      (47.8 versus 17.0%, P = 0.006) and composite perinatal morbidity (43.5 versus
      14.9%, P = 0.009). Logistic regression revealed the only independent predictors
      of spontaneous preterm birth <35 weeks were further cervical length shortening
      (adjusted odds ratio (aOR) 5.73; 95% confidence interval (CI) 1.31 to 24.43) and
      gestational age at short cervical length (aOR 0.95; 95% CI 0.91 to 0.99).
      CONCLUSION: Further cervical length shortening in asymptomatic high-risk women
      with a short cervical length is an important independent predictor of spontaneous
      preterm birth <35 weeks and perinatal morbidity.

PMID- 21183926
TI  - Perspectives on communication in labor and delivery: a focus group analysis.
AB  - OBJECTIVE: The objective of this study was to elicit and explore perceptions of
      barriers to optimal communication among clinicians on a labor and delivery unit,
      and to use this information to select and design approaches to improve
      communication. STUDY DESIGN: A qualitative research design using a focus group
      format was utilized. Attending and resident obstetricians and anesthesiologists,
      as well as staff nurses, pharmacists and unit secretaries participated in the
      focus groups, which were recorded and transcribed. Data were analyzed using a
      framework analysis approach. RESULT: In total, 18 focus groups with a total of 92
      participants were conducted. Eight key themes emerged regarding specific barriers
      to effective communication among clinicians in the labor and delivery setting.
      The most prominent of these themes included issues with inter-departmental
      coordination, clinical accessibility (the ability to reach other clinicians),
      lack of a consistent approach for clinical documentation, and the involvement of
      multiple care providers. On the basis of these themes, multiple interventions
      were designed to enhance communication. CONCLUSION: Focus group methodology can
      be used to elicit a detailed description of communication practices of clinicians
      on a labor and delivery unit, permitting an exploration of specific barriers to
      communication and the identification of potential solutions to those barriers.

PMID- 21183929
TI  - Ethnicity and arterial stiffness in Brazil.
AB  - BACKGROUND: The impact of increased central arterial stiffness as a predictor of
      morbidity and mortality, independently of other cardiovascular (CV) risk factors,
      has been established. The main aim of the present work was to investigate the
      association of ethnicity on arterial stiffness in different ethnic groups from
      the Brazilian population. METHODS: A total of 1,427 individuals from the general
      population were randomly selected from the Vitoria City metropolitan area and 588
      Amerindians from a native community in Brazil. The ethnicity of the general
      population was classified by a standard questionnaire as Caucasian descent,
      African descent, or Mulattos (considered racially mixed subjects). Pulse wave
      velocity (PWV) was measured with a noninvasive automatic device (Complior,
      Colson; Garges les Gonesses, France). RESULTS: Hemodynamic data of PWV, systolic
      blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure
      (MBP) was higher in African descent individuals than in the other groups (P <
      0.001). These results were still observed after adjustment for age and mean
      arterial pressure (P < 0.001). In addition, studying only normotensive
      individuals, PWV adjusted levels were higher in African descent individuals, and
      lower in Amerindians when compared with other ethnic groups (P < 0.01), showing,
      without the possible confounder effects of time and severity of hypertension or
      medication use, that PWV is associated with ethnicity in our population.
      CONCLUSION: The study of different ethnic groups from a highly admixtured
      population was able to demonstrate an association between ethnicity and arterial
      stiffness.

PMID- 21183928
TI  - Recombinant vascular endothelial growth factor 121 attenuates autoantibody
      induced features of pre-eclampsia in pregnant mice.
AB  - BACKGROUND: Pre-eclampsia (PE) is a serious hypertensive disorder of pregnancy
      characterized by excessive production of a soluble form of the vascular
      endothelial growth factor (VEGF) receptor-1, termed soluble fms-like tyrosine
      kinase-1 (sFlt-1). This placental-derived factor is believed to be a key
      contributor to the clinical features of PE. Women with PE are also characterized
      by the presence of autoantibodies, termed angiotensin type 1 receptor activating
      autoantibody (AT(1)-AA), that activate the major angiotensin receptor, AT(1).
      These autoantibodies cause clinical features of PE and elevated sFlt-1 when
      injected into pregnant mice. The research reported here used this autoantibody
      injection model of PE to assess the therapeutic potential of recombinant
      VEGF(121), a relatively stable form of the natural ligand. METHODS:
      Immunoglobulin G (IgG) from women with PE was injected into pregnant mice with or
      without continuous infusion of recombinant VEGF(121). Injected mice were
      monitored for symptoms of PE. RESULTS: As a result of infusion of recombinant
      VEGF(121) autoantibody-induced hypertension (systolic blood pressure) was reduced
      from 159 +/- 5 to 124 +/- 5 mm Hg, proteinuria from 111 +/- 16 to 40 +/- 5 mg
      protein/mg creatinine and blood urea nitrogen levels from 31 +/- 1 mg/dl to 18 +/
      2 mg/dl, P < 0.05. Histological analysis revealed that autoantibody-induced
      glomerular damage including the narrowing of Bowman's space and occlusion of
      capillary loop spaces was largely prevented by VEGF(121) infusion. Finally,
      impaired placental angiogenesis resulting from AT(1)-AA injection was
      significantly improved by VEGF(121) infusion. CONCLUSIONS: The infusion of
      recombinant VEGF(121) significantly attenuated autoantibody-induced features of
      PE.

PMID- 21183927
TI  - Physiologic and pharmacologic considerations for hypothermia therapy in neonates.
AB  - With mounting evidence that hypothermia is neuroprotective in newborns with
      hypoxic-ischemic encephalopathy (HIE), an increasing number of centers are
      offering this therapy. Hypothermia is associated with a wide range of physiologic
      changes affecting every organ system, and awareness of these effects is essential
      for optimum patient management. Lowering the core temperature also alters
      pharmacokinetic and pharmacodynamic properties of medications commonly used in
      asphyxiated neonates, necessitating close attention to drug efficacy and side
      effects. Rewarming introduces additional risks and challenges as the hypothermia
      associated physiologic and pharmacologic changes are reversed. In this review we
      provide an organ system-based assessment of physiologic changes associated with
      hypothermia. We also summarize evidence from randomized controlled trials showing
      lack of serious adverse effects of moderate hypothermia therapy in term and near
      term newborns with moderate-to-severe HIE. Finally, we review the effects of
      hypothermia on drug metabolism and clearance based on studies in animal models
      and human adults, and limited data from neonates.

PMID- 21183930
TI  - Association of subcutaneous and visceral adiposity with albuminuria: the
      Framingham Heart Study.
AB  - Microalbuminuria is a common condition associated with increased incidence of
      cardiovascular events and mortality. Abdominal obesity is associated with
      microalbuminuria, but studies linking visceral adipose tissue (VAT) and
      microalbuminuria are limited. Our objective was to determine the associations of
      albuminuria with VAT and subcutaneous adipose tissue (SAT). We performed a cross
      sectional study in the Framingham Multi-Detector Computed Tomography (MDCT)
      cohort (n = 3099, 48.2% women, mean age 53 years). VAT and SAT volumes were
      measured using computed tomography. Urinary albumin-to-creatinine ratio (UACR)
      was calculated from spot urine samples. Microalbuminuria was defined as a UACR
      >25 mg/g in women or >17 mg/g in men. Overall, 7.9% (n = 244) of the sample had
      microalbuminuria. Among men, VAT (odds ratio (OR) 1.48 per s.d., P < 0.0001) and
      SAT (OR 1.37 per s.d., P = 0.0002) were associated with microalbuminuria in
      minimally adjusted models, which remained significant after multivariable
      adjustment (VAT OR 1.34 per s.d., P = 0.001; SAT OR 1.28 per s.d., P = 0.005).
      Additionally, when considered jointly, VAT (P = 0.002) but not SAT (P = 0.2) was
      associated with microalbuminuria. In women, VAT was associated with
      microalbuminuria after minimal adjustment (OR 1.28, P = 0.01), but not after
      multivariable adjustment (OR 1.03, P = 0.8). In multivariable models in women,
      SAT was associated with a decreased odds of having microalbuminuria (OR 0.75 per
      s.d., P = 0.03). In conclusion, VAT is associated with microalbuminuria in men
      but not women. Albuminuria may be a manifestation of visceral adiposity.

PMID- 21183931
TI  - Long-term effects of a multidisciplinary treatment of uncomplicated obesity on
      carotid intima-media thickness.
AB  - Obesity is associated with well-known cardiovascular risk factors and a lower
      life expectancy. This study investigated whether nonoperative nutritional
      treatment of obesity without comorbidities influenced the carotid intima-media
      thickness (c-IMT) in the long run. Fifty-four subjects of an original cohort of
      251 subjects were re-evaluated 10 years after a medical nutritional treatment
      (MNT) with cognitive-behavioral approach for uncomplicated obesity. Forty
      subjects were classified as failure (10-year body weight change > 0.5 kg) and 14
      (body weight change <= 0.5 kg) as a success of the MNT. Ten years after MNT, c
      IMT significantly increased (0.06 +/- 0.02 mm; P = 0.004) in the failure group
      and significantly decreased (-0.07 +/- 0.03 mm; P = 0.027) in the success group.
      Ten-year change in c-IMT correlated significantly with 10-year change in body
      weight (r = 0.28; P = 0.040). Multiple stepwise linear regression analysis
      demonstrated that age, final BMI, and group (success or failure) influenced
      independently the 10-year c-IMT. In conclusion, this study is in agreement with
      the possibility that the successful MNT of obesity may be an effective choice in
      the long run and seems to indicate that it may be able to reduce the
      cardiovascular risk as reflected by the change in c-IMT.

PMID- 21183932
TI  - Multivariate linkage scan for metabolic syndrome traits in families with type 2
      diabetes.
AB  - The purpose of this study was to evaluate evidence for linkage to interrelated
      quantitative features of the metabolic syndrome (MetS). Data on eight
      quantitative MetS traits (body weight, waist circumference, systolic and
      diastolic blood pressure, high-density lipoprotein (HDL) cholesterol,
      triglycerides (TGs), and fasting glucose and insulin measurements) and a 10 cM
      genome scan were available for 78 white families (n = 532 subjects). These data
      were used to conduct multipoint, multivariate linkage analyses, including tests
      for coincident linkage and complete pleiotropy. The strongest evidence for
      linkage from the bivariate analyses was observed on chromosome 1 (1p22.2) (HDL
      TG; univariate lod score equivalent (lod(eq) = 3.99)) with stronger results from
      the trivariate analysis at the same location (HDL-TG-Insulin; lod(eq) = 4.32).
      Seven additional susceptibility regions (lod(eq) scores >1.9) were observed
      (1p36, 1q23, 2q21.2, 8q23.3, 14q23.2, 14q32.11, and 20p11.21). The results from
      this study indicate that several correlated traits of the MetS are influenced by
      the same gene(s) that account for some of the clustering of the MetS features.

PMID- 21183933
TI  - Association of BMI and cardiovascular risk stratification in the elderly African
      American females.
AB  - We aimed to estimate the association of BMI and risk of systemic hypertension in
      African-American females aged 65 years and older. In this retrospective, cross
      sectional study, medical charts were randomly reviewed after obtaining
      institutional review board approval and data collection was conducted for height,
      weight, BMI, age, ethnicity, gender, and hypertension. A multivariable logistic
      regression analysis was performed. The mean BMI was significantly higher in
      hypertensive subjects than normotensives (30.3 vs. 29 kg/m2; P = 0.003). A higher
      proportion of hypertensive subjects had a BMI >23 kg/m2 as compared to
      normotensives (88.9% vs. 83.5%; P = 0.023). When the log odds of having a history
      of hypertension was plotted against BMI as a continuous variable, we found that
      the odds showed an increasing trend with increasing BMI and a steep increase
      after a BMI of 23 kg/m2. When BMI was analyzed as a categorical variable, a BMI
      of 23-30 kg/m2 was found to have an odds ratio of 1.43 (95% confidence interval
      1.01-2.13; P = 0.05) and a BMI of >30 kg/m2 had an odds ratio of 1.76 (95%
      confidence interval 1.17-2.65; P = 0.007) when compared to a BMI of <23 kg/m2.
      This association remained significant in both univariate and multivariate
      analysis. We conclude that BMI is an independent predictor of hypertension in
      elderly African-American females. Our results indicate that the risk of
      hypertension increased significantly at BMI of >23 kg/m2 in this ethnic group.
      Weight reduction to a greater extent than previously indicated could play an
      integral role in prevention and control of high blood pressure in this particular
      population.

PMID- 21183934
TI  - Obesity is associated with reduced white matter integrity in otherwise healthy
      adults.
AB  - Existing work demonstrates that obesity is independently associated with
      cognitive dysfunction and macrostructural brain changes; however, little is known
      about the association between obesity and white matter (WM) integrity. We explore
      this relationship in a large cohort of otherwise healthy subjects. The present
      study classified 103 adult participants from the Brain Resource International
      Database between 21 and 86 years of age without history of neurological, medical,
      or psychiatric illness according to BMI (normal weight, overweight, obese) and
      subjected them to diffusion tensor imaging (DTI). Resulting fractional anisotropy
      (FA) indexes for the corpus callosum and fornix were examined in relation to BMI
      and age in a multiple regression framework. Results indicated that increasing BMI
      was independently associated with lower FA in the genu, splenium, and fornix, and
      a BMI * age interaction emerged for FA in the splenium and body of the corpus
      callosum. When categorized, obese persons demonstrated lower FA than normal and
      overweight persons for all WM indexes, but no FA differences emerged between
      overweight and normal persons. Results indicate both a direct association between
      obesity and reduced WM tract integrity and an interaction between obesity and
      aging processes on certain WM tracts in otherwise healthy adults. While such
      findings suggest a possible role for adiposity in WM dysfunction and associated
      cognitive deficits, prospective studies are needed to clarify the nature of these
      relationships and elucidate underlying mechanisms.

PMID- 21183935
TI  - Associations of visceral and liver fat with the metabolic syndrome across the
      spectrum of obesity: the AGES-Reykjavik study.
AB  - Visceral adipose tissue (VAT) is a key pathogenic fat depot in the metabolic
      syndrome (MetS), but liver fat (LF) may also play an important role. We evaluated
      associations of VAT and LF with MetS in normal weight, overweight, and obese men
      and women (BMI <25, 25-29.9, and >=30 kg/m2, respectively). This analysis
      included 2,495 participants from the Age, Gene/Environment Susceptibility (AGES)
      Reykjavik study with computed tomography measurements for VAT and LF. MetS was
      defined by >=3 of the following: larger abdominal circumference, hypertension,
      elevated triglyceride (TG), low high-density lipoprotein (HDL), impaired fasting
      glucose (IFG), and microalbuminuria. We estimated the odds of MetS per 1-s.d.
      increase in VAT and LF, adjusting for key covariates. VAT was associated with an
      increased odds of MetS in normal weight, overweight, and obese women (odds ratios
      (OR) = 2.78, 1.63, and 1.43, respectively; all P < 0.01) that diminished in
      magnitude with increasing BMI (VAT * BMI class interaction P < 0.001). In men,
      VAT was related to MetS only among the overweight (OR = 1.69, P < 0.01). LF was
      associated with MetS in the overweight and obese groups in women (OR = 1.38 and
      1.45; both P < 0.001) and in men (OR = 1.38, P = 0.01; and OR = 1.27, P = 0.10),
      but not in the normal weight groups. These BMI-specific relationships persisted
      when both fat depots were included in the model. VAT and LF were associated with
      MetS independently of each other, and these relationships were modified by BMI
      class such that, VAT was the more important depot at lower levels of obesity and
      LF at higher levels. Importantly, fatty liver may be a novel metabolic risk
      factor in overweight and obese individuals.

PMID- 21183936
TI  - High leptin/adiponectin ratio and serum triglycerides are associated with an "at
      risk" phenotype in young severely obese patients.
AB  - "At-risk" severely obese subjects are characterized by insulin resistance, and
      higher visceral fat and plasma lipid levels compared with metabolically healthy
      obese (MHO) subjects, although both groups have a high BMI and fat mass. The aim
      of this study was to measure several serum adipokines and gastrointestinal
      hormones in a young severely obese population from Southern Italy to identify
      biochemical markers of the "at-risk" insulin-resistant obese profile. We studied
      160 unrelated white young adults (mean age = 25.2 years, mean BMI = 44.9 kg/m(2),
      65% women) affected by obesity for at least 5 years. Serum concentrations of
      glucagon, ghrelin, gastric inhibitory peptide, glucagon like peptide-1,
      interleukin-6, tumor necrosis factor alpha, leptin, adiponectin, adipsin, and
      visfatin were measured. The leptin/adiponectin (L/A) ratio and fatty liver index
      (FLI) were calculated. We found a prevalence of 21.3% of MHO patients in our
      young severely obese patients. At univariate analysis, the "at-risk" group had
      higher mean levels of BMI (P < 0.0001), leptin (P = 0.039, men) and the L/A ratio
      (P = 0.003), and lower mean levels of visfatin (P = 0.026) than the MHO group.
      The L/A ratio, serum triglycerides, and male sex were significantly associated
      with "at-risk" obesity and accounted for 19.5% of insulin resistance at
      multivariate analysis. In conclusion, we demonstrate that a high serum L/A ratio
      and high levels of serum triglycerides may be markers of "at-risk" obesity,
      independent of waist circumference (WC) and BMI, in young severely obese
      population.

PMID- 21183937
TI  - Effect of diet with and without exercise training on markers of inflammation and
      fat distribution in overweight women.
AB  - The independent effects of exercise and weight loss on markers of inflammation
      (MOI) in obese individuals have not been clearly characterized. The objectives of
      this study were to: (i) identify the independent effects of exercise and weight
      loss on MOI and (ii) determine whether changes in MOI were associated with
      changes in fat distribution. Subjects were 126 healthy, premenopausal women, BMI
      27-30 kg/m(2). They were randomized to one of three groups: diet only, diet +
      aerobic-, or diet + resistance training until a BMI <25 kg/m(2) was achieved. Fat
      distribution was measured with computed tomography, and body composition with
      dual-energy X-ray absorptiometry. Serum concentrations of tumor necrosis factor
      (TNF)-alpha, soluble TNF receptor 1 (sTNF-R1), soluble TNF receptor 2 (sTNF-R2),
      C-reactive protein (CRP), and interleukin (IL)-6 were assessed. Results of
      repeated-measures ANOVA indicated a significant effect of time on MOI, such that
      MOI decreased with weight loss. Results of mixed-model analysis indicated that
      adjusting for intra-abdominal adipose tissue (IAAT) and total fat mass explained
      the decreases in TNF-alpha and sTNF-R1, whereas only total fat mass explained the
      decreases in sTNF-R2, IL-6, and CRP. In conclusion, weight loss was associated
      with decreases in MOI. The effect of weight loss appeared to be mediated by
      changes in total fat mass or IAAT. Addition of exercise did not alter the
      response, suggesting that weight loss has a more profound impact for reducing MOI
      in overweight women than exercise.

PMID- 21183939
TI  - HOXB7 expression by myeloma cells regulates their pro-angiogenic properties in
      multiple myeloma patients.
AB  - The deregulation of the homeobox genes as homeoboxB (HOXB)-7 has been previously
      associated to tumor progression and angiogenesis; here we investigated the
      potential role of HOXB7 in the pro-angiogenic properties of multiple myeloma (MM)
      cells. We found that HOXB7 was expressed in 10 out of 22 MM patients analyzed at
      the diagnosis related to high bone marrow angiogenesis and overexpressed in about
      40% of myeloma cell lines compared with normal plasma cells. Enforced HOXB7
      expression in MM cells by a lentiviral vector significantly modified their
      transcriptional and angiogenic profile, checked by combined microarray and
      angiogenesis PCR analyses, upregulating VEGFA, FGF2, MMP2, WNT5a and PDGFA and
      downregulating thrombospoindin-2. The pro- and anti-angiogenic HOXB7-related gene
      signature was also validated in a large independent dataset of MM patients.
      Accordingly, MM-induced vessel formation was significantly increased by HOXB7
      overexpression both in vitro angiogenic and chorioallantoic membrane assays, as
      well as the HOXB7 silencing by small interfering RNA inhibited the production of
      angiogenic factors, and the pro-angiogenic properties of MM cells. Finally, in
      SCID-NOD mice we confirmed that HOXB7 overexpression by MM cells stimulated tumor
      growth, increased MM-associated angiogenesis and the expression of pro-angiogenic
      genes by microarray analysis supporting the critical role of HOXB7 in the
      angiogenic switch in MM.

PMID- 21183938
TI  - Sequence-specific regulator Prdm14 safeguards mouse ESCs from entering
      extraembryonic endoderm fates.
AB  - Prdm14 is a PR-domain and zinc-finger protein whose expression is restricted to
      the pluripotent cells of the early embryo, embryonic stem cells (ESCs), and germ
      cells. Here, we show that Prdm14 safeguards mouse ESC (mESC) maintenance by
      preventing induction of extraembryonic endoderm (ExEn) fates. Conversely, Prdm14
      overexpression impairs ExEn differentiation during embryoid body formation.
      Prdm14 occupies and represses genomic loci encoding ExEn differentiation factors,
      while also binding to and promoting expression of genes associated with mESC self
      renewal. Prdm14-associated genomic regions substantially overlap those occupied
      by Nanog and Oct4, are enriched in a chromatin signature associated with distal
      regulatory elements and contain a unique DNA-sequence motif recognized by Prdm14
      in vitro. Our work identifies a new member of the mESC transcriptional network,
      Prdm14, which plays a dual role as a context-dependent transcriptional repressor
      or activator.

PMID- 21183940
TI  - Comparison of retinal nerve fiber layer measured by time domain and spectral
      domain optical coherence tomography in optic neuritis.
AB  - PURPOSE: To study the relationship between retinal nerve fiber layer (RNFL)
      thickness measurements from time domain (Stratus) and spectral domain (Cirrus HD)
      optical coherence tomography (OCT) in subjects with optic neuritis. METHODS: A
      total of 18 patients who had suffered monocular acute optic neuritis were imaged
      by a single trained operator using the Stratus-OCT (fast RNFL scan mode) and
      Cirrus HD-OCT (optic disc cube mode) on the same day. The relationship between
      RNFL thickness measurements of the two OCTs (overall and by quadrants) were
      evaluated using intraclass correlation coefficient (ICC) and Bland-Altman plots.
      Comparisons between eyes having optic neuritis (ON-group) and fellow eyes (fellow
      group) were assessed by a generalized estimating equation (GEE) regression model.
      RESULTS: For Stratus-OCT, the median average RNFL was 86.3 and 102 MU in the ON
      group and in the fellow-group, respectively. For Cirrus-OCT, the corresponding
      measurements were 81 and 93 MU. Average RNFL thickness as determined by the two
      OCT devices was well correlated in the ON-group (rho = 0.906, P< 0.001) and in
      the fellow-group (rho = 0.702, P = 0.001). The median signal strength was
      significantly higher with Cirrus-OCT. Bland-Altman plots showed that Stratus RNFL
      measurements were larger than Cirrus-OCT, but smaller when average RNFL thickness
      was very thin (<= 56 MU). CONCLUSIONS: Although the Cirrus-OCT and Stratus-OCT
      RNFL thickness measurements are well correlated in patients with optic neuritis,
      RNFL measurements cannot be directly compared. Clinicians should be aware that
      measurements are generally higher with Stratus- than with Cirrus-OCT.

PMID- 21183942
TI  - Earlier stage of myopic foveoschisis documented by optical coherence tomography.
      Reply to Loh and Wong.

PMID- 21183941
TI  - The role of anti-inflammatory agents in age-related macular degeneration (AMD)
      treatment.
AB  - Although age-related macular degeneration (AMD) is not a classic inflammatory
      disease like uveitis, inflammation has been found to have an important role in
      disease pathogenesis and progression. Innate immunity and autoimmune components,
      such as complement factors, chemokines, cytokines, macrophages, and ocular
      microglia, are believed to be heavily involved in AMD development. Targeting
      these specific inflammatory molecules has recently been explored in an attempt to
      better understand and treat AMD. Although antivascular endothelial growth factor
      therapy is the first line of defence against neovascular AMD, anti-inflammatory
      agents such as corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs),
      immunosuppressive agents (eg, methotrexate and rapamycin), and biologics (eg,
      infliximab, daclizumab, and complement inhibitors) may provide an adjunct or
      alternative mechanism to suppress the inflammatory processes driving AMD
      progression. Further investigation is required to evaluate the long-term safety
      and efficacy of these drugs for both neovascular and non-neovascular AMD.

PMID- 21183943
TI  - Pattern electroretinogram association with spectral domain-OCT structural
      measurements in glaucoma.
AB  - PURPOSE: To describe the association between pattern electroretinogram (PERG)
      amplitude and spectral domain-optical coherence tomography (SD-OCT) macular
      thickness, retinal nerve fibre layer (RNFL) thickness and optic disc topography
      measurements. SUBJECTS AND METHODS: Both eyes (n = 132) of 66 glaucoma patients
      (mean age = 67.9 years) enrolled in the University of California, San Diego, CA,
      USA, Diagnostic Innovations in Glaucoma Study (DIGS) were included. Eyes were
      tested with PERG (Glaid PERGLA, Lace Elettronica, Pisa, Italy), RTVue SD-OCT
      (Optovue Inc., Fremont, CA, USA) GCC, and NHM4 protocols on the same day. Of the
      66 enrolled patients, 43 had glaucoma defined by repeated abnormal standard
      automated perimetry (SAP) results in at least one eye and 23 were glaucoma
      suspects defined by a glaucomatous-appearing optic disc by physicians'
      examination in at least one eye and normal SAP results in both eyes. Associations
      (R(2)) were determined between PERG amplitude (MUV) and SD-OCT macular ganglion
      cell complex (GCC) thickness (MUm), macular thickness (MUm), macular outer
      retinal thickness (macular thickness minus GCC thickness) (MUm), RNFL thickness
      (MUm), neuroretinal rim area (mm(2)), and rim volume (mm(3)). RESULTS: PERG
      amplitude was significantly associated with GCC thickness (R(2) = 0.179, P <
      0.001), RNFL thickness (R(2) = 0.174, P < 0.001), and macular thickness (R(2) =
      0.095, P<0.001). R(2) associations with other parameters were not significant
      (all P > 0.624). Significant associations remained for GCC and average RNFL
      thickness when age and intraocular pressure at the time of testing were included
      in multivariate models (both P <= 0.030). CONCLUSIONS: PERG amplitude is
      significantly (but weakly) associated with macular GCC thickness, RNFL thickness,
      and macular thickness. The lack of association between PERG amplitude and macular
      outer retinal thickness supports previous results, possibly suggesting that that
      the PERG is driven primarily by retinal ganglion cell (inner retinal) responses.

PMID- 21183944
TI  - Cost effectiveness of the type II Boston keratoprosthesis.
AB  - PURPOSE: Despite demonstrated cost effectiveness, not all corneal disorders are
      amenable to type I Boston keratoprosthesis (KPro) implantation. This includes
      patients with autoimmune diseases, such as Stevens-Johnson syndrome/toxic
      epidermal necrolysis. Type II KPro is implanted through the eyelids in severe dry
      eye and cicatricial diseases, and its cost effectiveness was sought. PATIENTS AND
      METHODS: In a retrospective chart review, 29 patients who underwent type II KPro
      surgery at the Massachusetts Eye and Ear Infirmary between the years 2000 and
      2009 were identified. A total of 11 patients had 5-year follow-up data. Average
      cost effectiveness was determined by cost-utility analysis, comparing type II
      KPro surgery with no further intervention. RESULTS: Using the current parameters,
      the cost utility of KPro from third-party insurer (Medicare) perspective was
      63,196 $/quality-adjusted life year . CONCLUSION: Efforts to refer those less
      likely to benefit from traditional corneal transplantation or type I KPro, for
      type II KPro surgery, may decrease both patient and societal costs.

PMID- 21183945
TI  - Prevalence of pinguecula and pterygium in a general population in Spain.
AB  - PURPOSE: To determine the prevalence of pinguecula and pterygium and to
      investigate their associations in a general adult population in North-Western
      Spain. METHODS: An age-stratified random sample of 1155 subjects >= 40 years was
      selected in O Salnes (Spain). From 937 eligible subjects, 619 (66.1%)
      participated (mean age (SD): 63.4 (14.5) years, range: 40-96 years, 37.0% males).
      An interview to collect history of systemic diseases and lifestyle details and a
      comprehensive ophthalmic evaluation in which pinguecula and pterygium were
      recorded was carried out. The prevalence of pinguecula and pterygium and their
      relationship with lifestyle factors and ocular and systemic diseases was
      investigated. RESULTS: The prevalence of pinguecula was 47.9% (95% confidence
      interval (CI): 43.9-51.9). This prevalence increased significantly with aging (P
      = 0.002) and was higher in men (56.4%; 95% CI: 50.0-62.7) than in women (42.7%;
      95% CI: 37.8-47.8) (P=0.001). The prevalence of pterygium was 5.9% (95% CI: 4.3
      7.9). This prevalence also increased significantly with aging (P = 0.005) and was
      4.8% (95% CI: 2.6-8.4) in men and 6.5% (95% CI: 4.5-9.3) in women (P = 0.346).
      After controlling for age and sex, pinguecula was associated with alcohol intake
      (adjusted odds ratio (OR(a)): 3.08; 95% CI: 1.60-5.95), pterygium with
      fluorescein staining (OR(a): 2.64; 95% CI: 1.08-6.46) and both disorders with
      outer activity (OR(a): 2.07; 95% CI: 1.36-3.15 and 2.28; 95% CI: 1.04-4.98,
      respectively). CONCLUSIONS: Pinguecula is far more common than pterygium. Alcohol
      consumption is strongly associated with pinguecula. Fluorescein staining is
      highly prevalent in subjects with pterygium. Both disorders increase with age and
      are associated with outer activity.

PMID- 21183947
TI  - Oncolytic adenovirus based on serotype 3.
AB  - Oncolytic adenoviruses have been safe in clinical trials but the efficacy has
      been mostly limited. All published trials have been performed with serotype 5
      based viruses. The expression level of the Ad5 receptor CAR may be variable in
      advanced tumors. In contrast, the Ad3 receptor remains unclear, but is known to
      be abundantly expressed in most tumors. Therefore, we hypothesized that a fully
      serotype 3 oncolytic adenovirus might be useful for treating cancer. Patients
      exposed to adenoviruses develop high titers of serotype-specific neutralizing
      antibodies, which might compromise re-administration. Thus, having different
      serotype oncolytic viruses available might facilitate repeated dosing in humans.
      Ad3-hTERT-E1A is a fully serotype 3 oncolytic adenovirus controlled by the
      promoter of the catalytic domain of human telomerase. It was effective in vitro
      on cell lines representing seven major cancer types, although low toxicity was
      seen in non-malignant cells. In vivo, the virus had anti-tumor efficacy in three
      different animal models. Although in vitro oncolysis mediated by Ad3-hTERT-E1A
      and wild-type Ad3 occurred more slowly than with Ad5 or Ad5/3 (Ad3 fiber knob in
      Ad5) based viruses, in vivo the virus was at least as potent as controls. Anti
      tumor efficacy was retained in presence of neutralizing anti-Ad5 antibodies
      whereas Ad5 based controls were blocked. In summary, we report generation of a
      non-Ad5 based oncolytic adenovirus, which might be useful for testing in cancer
      patients, especially in the context of high anti-Ad5 neutralizing antibodies.

PMID- 21183948
TI  - Treatment of patient tumor-derived colon cancer xenografts by a TRAIL gene-armed
      oncolytic adenovirus.
AB  - Oncolytic virus-armed gene therapy may offer new treatment options and improve
      the prognosis for patients with colon cancer. In this study, we sought to further
      confirm the antitumor activity of oncolytic virus-armed tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) gene therapy in xenografts, which
      derived from the tumors of patients with colon cancer. To this end, we
      established xenotransplantable tumors from fresh surgical specimens. The
      histology of these xenografts maintained the features of the original tumors
      during passaging in nude mice. We next treated these xenografts with adenoviruses
      carrying TRAIL and the adenovirus E1A gene (Ad/TRAIL-E1) driven by the human
      telomerase reverse transcriptase promoter. The vector expressing the TRAIL gene
      (Ad/gTRAIL) or the E1A gene (Ad/GFP-E1) alone was used as control vector. The
      results demonstrated that Ad/TRAIL-E1 had more significant inhibitory effects on
      tumor growth than Ad/gTRAIL or Ad/GFP-E1 alone. Furthermore, we did not find any
      obvious treatment-related toxicity in the mice. Our results indicate that the use
      of an oncolytic adenoviral vector, in combination with TRAIL gene therapy, is a
      promising novel approach for cancer therapy.

PMID- 21183946
TI  - Retargeting adenoviral vectors to improve gene transfer into tumors.
AB  - Gene targeting to tumors using adenoviral (Ad) vectors holds great potential for
      cancer imaging and therapy, but the limited efficacy of current methods used to
      improve delivery to target tissues and reduce unwanted interactions remain
      substantial barriers to further development. Progress in characterizing the set
      of molecular interactions used by Ad vectors to infect particular tissues has
      aided the development of novel strategies for retargeting vectors to tumor cells.
      One method is chemical retargeting of adenovirus using bispecific antibodies
      (bsAbs) against both viral capsid proteins and tumor-specific cell surface
      molecules. This approach can be combined either with competitive inhibitors
      designed to reduce viral tropism in undesired tissues, or with traditional
      therapeutics to increase the expression of surface molecules for improved tumor
      targeting. Ablating liver cell-specific interactions through mutation of capsid
      proteins or chemical means are promising strategies for reducing adenovirus
      induced liver toxicity. The nature of tumor neovasculature also influences Ad
      delivery, and the use of vascular disrupting agents (VDAs) such as combretastatin
      can help elucidate these contributions. In this investigation, we evaluate a
      variety of these methods for retargeting Ad vectors to tumor cells in vitro and
      in vivo, and assess the contributions of specific molecular and tissue
      interactions that affect Ad transgene delivery.

PMID- 21183949
TI  - Direct gene transfer of adenoviral-mediated interferon alpha into human bladder
      cancer cells but not the bystander factors produced induces endoplasmic reticulum
      stress-related cytotoxicity.
AB  - We have previously shown that adenoviral-mediated interferon alpha (Ad-IFNalpha)
      is cytotoxic both to cells that are sensitive to recombinant interferon alpha
      (IFNalpha) and to cells which are resistant to IFNalpha. The cancer cell-specific
      cytotoxic effects of Ad-IFNalpha involve three different mechanisms: 1. The
      direct effect of IFNalpha production causing cancer cell death in IFNalpha
      sensitive cells (1); 2. The direct effect of Ad-IFNalpha infection and high
      levels of IFNalpha expression in IFNalpha resistant cancer cells (2); and 3. The
      indirect effect of the Ad-IFNalpha bystander factors produced (2-4). After Ad
      IFNalpha infection, the cells produce a large amount of perinuclear localized IFN
      protein. This protein over-load could be a major factor in the direct cancer cell
      death of those cells infected with Ad-IFNalpha compared with the indirect
      cytotoxic effects of the bystander factors produced. Here, we investigated
      whether a component of Ad-IFN-induced cell death involves protein overload
      induced endoplasmic reticulum (ER) stress, using an IFNalpha-resistant human
      bladder cancer cell line (KU7), and the normal human urothelial cell line, TERT
      NHUC, as preclinical models. We found that the two ER stress response pathways
      examined were activated in KU7 cells. In contrast, following treatment of the
      normal TERT-NHUC cells with Ad-IFNalpha, no ER stress signals were observed. In
      addition, no ER stress related changes were seen, when KU7 cells were exposed to
      conditioned medium from Ad-IFNalpha-treated KU7 cells, indicating that bystander
      produced cytotoxicity did not involve ER stress. After 24 h of Ad-IFNalpha
      infection, the KU7 cancer cells produced spliced X-box binding protein 1 and
      activating transcription factor 6 protein (ATF6), evoking an ER stress response
      that could contribute to Ad-IFNalpha induced apoptosis in these cancer cells. In
      addition, GADD153/CHOP, GADD34 and BAX were also subsequently modified following
      activation of the ER stress pathways, thereby signaling downstream effectors in a
      pro-apoptotic manner.

PMID- 21183950
TI  - Transfection of NF-kappaB decoy oligodeoxynucleotide suppresses pulmonary
      metastasis by murine osteosarcoma.
AB  - Nuclear factor-kappa B (NF-kappaB) has a pivotal role in the progression and
      distant metastasis of cancers, including malignant bone tumors. To inhibit NF
      kappaB activation, a new molecular therapy using synthetic double-stranded
      oligodeoxynucleotide (ODN) as a 'decoy' cis element against NF-kappaB has been
      developed. To determine whether pulmonary metastasis of osteosarcoma is reduced
      by inhibiting the action of NF-kappaB, NF-kappaB decoy ODN was transfected into
      the nuclei of murine osteosarcoma cells with high pulmonary metastatic potential,
      the LM8 cell line, using a three-dimensional alginate spheroid culture model. An
      in vitro study demonstrated the successful transfection of LM8 cells cultured in
      alginate beads by 'naked' NF-kappaB decoy ODN and that the activation of NF
      kappaB signaling was significantly suppressed. Tumor growth was not affected by
      transfection of NF-kappaB decoy ODN, however, the expression of vascular
      endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1)
      mRNA was markedly decreased. Furthermore, the transfection of 'naked' NF-kappaB
      decoy ODN effectively suppressed pulmonary metastasis in an in vivo alginate bead
      transplantation model. Our results suggest that NF-kappaB has a central and
      specific role in the regulation of tumor metastasis and could be a molecular
      target for development of anti-metastatic treatments for osteosarcoma.

PMID- 21183951
TI  - The role of in vivo T-cell depletion on reduced-intensity conditioning allogeneic
      stem cell transplantation from HLA-identical siblings in patients with follicular
      lymphoma.

PMID- 21183952
TI  - Janus kinase 2 regulates Bcr-Abl signaling in chronic myeloid leukemia.
AB  - Despite the success of imatinib mesylate (IM) in the early chronic phase of
      chronic myeloid leukemia (CML), patients are resistant to IM and other kinase
      inhibitors in the later stages of CML. Our findings indicate that inhibition of
      Janus kinase 2 (Jak2) in Bcr-Abl+ cells overcomes IM resistance although the
      precise mechanism of Jak2 action is unknown. Knocking down Jak2 in Bcr-Abl+ cells
      reduced levels of the Bcr-Abl protein and also the phosphorylation of Tyr177 of
      Bcr-Abl, and Jak2 overexpression rescued these knockdown effects. Treatment of
      Bcr-Abl+ cells with Jak2 inhibitors for 4-6 h but not with IM also reduced Bcr
      Abl protein and pTyr177 levels. In vitro kinase experiments performed with
      recombinant Jak2 showed that Jak2 readily phosphorylated Tyr177 of Bcr-Abl (a
      Jak2 consensus site, YvnV) whereas c-Abl did not. Importantly, Jak2 inhibition
      decreased pTyr177 Bcr-Abl in immune complexes but did not reduce levels of Bcr
      Abl, suggesting that the reduction of Bcr-Abl by Jak2 inhibition is a separate
      event from phosphorylation of Tyr177. Jak2 inhibition by chemical inhibitors
      (TG101209/WP1193) and Jak2 knockdown diminished the activation of Ras, PI-3
      kinase pathways and reduced levels of pTyrSTAT5. These findings suggest that Bcr
      Abl stability and oncogenic signaling in CML cells are under the control of Jak2.

PMID- 21183953
TI  - Gcn4p-mediated transcriptional repression of ribosomal protein genes under amino
      acid starvation.
AB  - Gcn4p is a well-characterized bZIP transcription factor that activates more than
      500 genes encoding amino acids and purine biosynthesis enzymes, and many stress
      response genes under various stress conditions. Under these stresses, it had been
      shown that transcriptions of ribosomal protein (RP) genes were decreased.
      However, the detailed mechanism of this downregulation has not been elucidated.
      In this study, we present a novel mechanistic model for a repressive role of
      Gcn4p on RP transcription, especially under amino-acid starvation. It was found
      that Gcn4p bound directly to Rap1p, which in turn inhibited Esa1p-Rap1p binding.
      The inhibition of Esa1p recruitment to RP promoters ultimately reduced the level
      of histone H4 acetylation and RP transcription. These data revealed that Gcn4p
      has simultaneous dual roles as a repressor for RP genes as well as an activator
      for amino-acid biosynthesis genes. Moreover, our results showed evidence of a
      novel link between general control of amino-acid biosynthesis and ribosome
      biogenesis mediated by Gcn4p at an early stage of adaptation to amino-acid
      starvation.

PMID- 21183954
TI  - The highly conserved KEOPS/EKC complex is essential for a universal tRNA
      modification, t6A.
AB  - The highly conserved Kinase, Endopeptidase and Other Proteins of small Size
      (KEOPS)/Endopeptidase-like and Kinase associated to transcribed Chromatin (EKC)
      protein complex has been implicated in transcription, telomere maintenance and
      chromosome segregation, but its exact function remains unknown. The complex
      consists of five proteins, Kinase-Associated Endopeptidase (Kae1), a highly
      conserved protein present in bacteria, archaea and eukaryotes, a kinase (Bud32)
      and three additional small polypeptides. We showed that the complex is required
      for a universal tRNA modification, threonyl carbamoyl adenosine (t6A), found in
      all tRNAs that pair with ANN codons in mRNA. We also showed that the bacterial
      ortholog of Kae1, YgjD, is required for t6A modification of Escherichia coli
      tRNAs. The ATPase activity of Kae1 and the kinase activity of Bud32 are required
      for the modification. The yeast protein Sua5 has been reported previously to be
      required for t6A synthesis. Using yeast extracts, we established an in vitro
      system for the synthesis of t6A that requires Sua5, Kae1, threonine, bicarbonate
      and ATP. It remains to be determined whether all reported defects of KEOPS/EKC
      mutants can be attributed to the lack of t6A, or whether the complex has multiple
      functions.

PMID- 21183955
TI  - Fis1 and Bap31 bridge the mitochondria-ER interface to establish a platform for
      apoptosis induction.
AB  - The mitochondria and the endoplasmic reticulum (ER) are two organelles that
      critically contribute to apoptosis induction. While it is established that they
      communicate, how cell death signals are transmitted from the mitochondria to the
      ER is unknown. Here, we show that the mitochondrial fission protein Fission 1
      homologue (Fis1) conveys an apoptosis signal from the mitochondria to the ER by
      interacting with Bap31 at the ER and facilitating its cleavage into the pro
      apoptotic p20Bap31. Exogenous apoptosis inducers likewise use this signalling
      route and induce the procession of Bap31. Moreover, we show that the recruitment
      of procaspase-8 to the Fis1-Bap31 platform is an early event during apoptosis
      induction. The association of procaspase-8 with the Fis1-Bap31 complex is
      dependent on the variant of death effector domain (vDED) in Bap31 and is required
      for the activation of procaspase-8. This signalling pathway establishes a
      feedback loop by releasing Ca(2+) from the ER that activates the mitochondria for
      apoptosis. Hence, the Fis1-Bap31 complex (ARCosome) that spans the mitochondria
      ER interface serves as a platform to activate the initiator procaspase-8, and
      thereby bridges two critical organelles for apoptosis signalling.

PMID- 21183957
TI  - [Objectives and methodology of S.E.N-ONT guidelines for living donor kidney
      transplantation].

PMID- 21183956
TI  - SUMO-specific protease 2 in Mdm2-mediated regulation of p53.
AB  - Genetic analysis in mice has revealed a key genetic pathway, SUMO-specific
      protease 2 (SENP2)-Mdm2-p53, essential for trophoblast development. Targeted
      disruption of SENP2 impairs the G-S transition required for mitotic and
      endoreduplication cell cycles during the expansion of trophoblast stem cells and
      their differentiation into polyploidy cells, respectively. The disruption
      disturbed the subcellular distribution and SUMO modification of Mdm2, leading to
      interference with p53 degradation. Here, we further explore the mechanism
      underlying SENP2-mediated regulation of Mdm2 in p53-induced cellular stress. We
      identify a specific isoform of SENP2 necessary and sufficient to negatively
      regulate the p53-dependent transcription and its related stress responses. This
      isoform-specific effect is attributed to the differential compartmentalization of
      SENP2. SUMO conjugation of Mdm2 induces its co-localization and association with
      SENP2 in promyelocytic leukemia bodies. Biochemical studies show that SENP2
      catalyzes the desumoylation process of Mdm2. SENP2-dependent regulation of Mdm2
      is sensitive to its p53-binding activity. Our findings led us to propose a
      mechanism underlying the SENP2-mediated regulation of Mdm2 that is critical for
      genome integrity in p53-dependent stress responses.

PMID- 21183958
TI  - [Present situaltion of living-donor kidney transplantation in Spain and other
      countries: past, present and future of an excellent therapeutic option].
AB  - Kidney transplantation from living donor is an established treatment in Spain
      since the 60s but has maintained a low level of activity until 2000, when the
      number of procedures and hospitals that perform this therapy experienced a
      gradual increase, reaching the highest figure in our history in 2009, with 235
      living donor kidney transplants (which represents 10% of renal transplant
      activity). The reasons why living donor kidney transplantation is emerging in our
      country are diverse and can be focused in four main areas. 1) Better outcomes
      obtained when using living donors for kidney transplantation than those obtained
      with kidneys from deceased donors. Younger recipients with better HLA matching,
      the good health of the donor, the absence of any damages that occur in the kidney
      secondary to brain death, the small ischemic time and the possibility of
      preemptive transplantation can explain the best graft and patient survival. 2)
      The scarcity of sources: the relaxation of entry criteria on the waiting list
      implies an increasing challenge of the demand for transplant without the
      contribution of living donor kidney transplantation, especially in young
      recipients where the chances of obtaining an age-appropriate deceased donor are
      lower, due to the change in the profile of the deceased donor (increasingly
      older). 3) Improvement in the safety of the donor: the excellent evaluation and
      monitoring of donors (based on international standards) plus the use of less
      invasive surgical techniques are related to a low complication rate and to
      survival expectancies of living donors being similar to those of the general
      population. 4) Barriers overcome: The training effort by the transplant teams,
      hospital and regional coordinations, and the National Transplant Organization is
      giving excellent results, visible in the gradual increase in the number of
      hospitals with a program of living donor kidney transplantation and its activity.
      In addition, desensitization programs and the national cross-over kidney
      transplantation program have removed barriers to transplantation in cases of ABO
      incompatibility or positive crossmatch.

PMID- 21183959
TI  - [Ethical aspects of living-donor kidney transplantation].
AB  - Living donor kidney transplantation is considered an established treatment for
      end-stage renal failure and is accepted in different transplant forums,
      nationally and internationally, while ensuring the safety of the donation, the
      information, the motivation and caring, the free consent and the absence profit.
      SAFETY: the living donor nephrectomy is not extent of risks so a good assessment
      of the donor's health status and psychosocial situation must be performed to
      evaluate if the benefits to donor and recipient outweigh the risks assumed.
      Information and Consent: to be considered ethically acceptable, the donor must be
      able to give his free consent to the donation after understanding the information
      provided, accepting the risks and benefits of organ donation, knowing the
      treatment alternatives for the recipient and the long-term consequences of his
      decision The absence of profit: offering or receiving money for an organ or other
      human tissue violates the principles of justice and equity and it is considered
      ethically and legally unacceptable MOTIVATION: it is important to make a good
      psychosocial assessment to identify whether the motivation is altruistic or not
      and, in other terms, to detect any kind of coercion (ex, in the family). Living
      donation must not be offered in desperate family situations so it is important to
      assess family relationships to rule out the absence of freedom in donor's
      choice.The Role of Health Care Ethics Committees: there exists a normative in our
      country that regulates living donation and establishes that the hospital ethics
      committees should participate in the process of living donation in all cases.
      Their job is to assess the process and develop a report on the donor free consent
      to donation. The responsible person of the living transplant program should
      provide the documentation necessary to the committee. An interview with the
      potential donor can be required in some cases.

PMID- 21183960
TI  - [Regulatory bases of living-donor kidney transplantation].
AB  - Living donor kidney transplantation is regulated in Spain by the transplantation
      law 30/1979 and developed by Royal Decree 2070/1999. These policies permit the
      living donation of an organ while its function is compensated by the rest of the
      body. It further specifies that the destination of the organ must be the
      transplantation in a specific person (this specification allows for the donation,
      not only among emotionally related, but between people that do not know each
      other, provided it is done altruistically, without any purpose of profit and
      without coercion). The donor must be competent, healthy and had reached 18 years
      old (which is evidenced by a medical certificate) and should be well informed of
      the consequences of their decision. The donor must give their consent to
      donation, free from inducement and consciously in the courts of civil
      registration. In order to guarantee the quality and safety of the procedure, the
      centers that performed this therapeutic must be authorized both for the
      nephrectomy and the transplantation.

PMID- 21183961
TI  - [Indications and contraindications of living-donor kidney transplantation].
AB  - Kidney transplant is the best therapy to manage end-stage kidney failure. The
      main barriers limiting this therapy are scarcity of cadaveric donors and the
      comorbidities of the patients with end-stage kidney failure, which prevent the
      transplant. Living kidney donor transplant makes it possible to obviate the
      problem of scarcity of cadaveric donor organs and also presents better results
      than the cadaveric transplant. The principal indication of living kidney donor
      transplant is preemptive transplant. This will allow the patient to avoid the
      complications of dialysis and it has also been demonstrated that it has better
      results than the transplant done after dialysis has been initiated. Priority
      indications of living donor transplant are also univitelline twins and HLA
      identical siblings. We will also have very favorable conditions when the donor is
      young and male. On the contrary, the living donor transplant will have worse
      results if the donors are over 60-65 years and the recipients are young, this
      possibly being a relative contraindication. There is an absolute contraindication
      for the living donation when the recipient has diseases with high risk of
      aggressive relapse in the grafts: focal and segmental hyalinosis that have had
      early relapse in the first transplant; atypical hemolytic uremic syndrome due to
      deficit or malfunction of the complement regulatory proteins; early development
      of glomerulonephritis due to anti-glomerular basement membrane antibody in
      patients with Alport Syndrome; primary hyperoxaluria.

PMID- 21183962
TI  - [Patient information: when and what].
AB  - The living donor kidney transplant should be considered a priority option
      providing better quality of life and survival for those needing renal replacement
      therapy. To increase their number, both nephrologists and patients, should be
      informed more and better, offering this option compared with LDKT alternatives
      (dialysis or kidney transplant from a deceased donor). The clinical nephrology
      consultations or specific pre-dialysis are the space where in stages 3 and 4 of
      renal failure should be started on LDKT informational approaches. Later, when
      seeking more detailed information and/or evaluation of potential donors, this
      could be provided at times and spaces specifically reserved for awareness
      professionals with the use of brochures or Internet addresses. Information should
      focus especially on the additional benefits of pre-emptive LDKT, the risks of
      nephrectomy and long term controls for the donor. Finally, donor, recipient and
      family should know that the donation will only be justified and may be accepted
      if the studies of risk/benefit for the donor and recipient have been faithfully
      evaluated according to the highest ethical standards.

PMID- 21183963
TI  - [Assessment and selection of kidney living donors].
AB  - Donor protection should always be taken account during the selection and
      assessment of a living donor. On these terms, the evaluation of a potential donor
      must include these issues: 1) The donor act is altruistic, consciousness and out
      of coercion; 2) Life expectancy and quality of life of the recipient will improve
      after the living donor kidney transplantation; 3) The donor has normal renal
      function and the potential risk of developing nephropathy in the long term follow
      up is scarce (familiar nephropathies and other processes that may increase the
      potential risk for renal disease in the future, like severe hypertension,
      diabetes, etc must be ruled out). The glomerular filtrate should meet criteria
      for the normal function corresponding to age furthermore the absence of
      proteinuria and urine smear is normal; 4) The screening in the donor should
      contemplate those clinical situations or diseases non related to the kidney
      function but might elevate the surgical and/or anesthesia risk besides disease
      transmission to the recipient (as neoplasia or infections); 5) The surgical act
      is possible without technical difficulties and always performed after a negative
      result of the crossmatch between donor and recipient. The living donor evaluation
      process will follow a different schedule based on each particular case and the
      center facilities. Any case, the mentioned process is divided in two parts: The
      first one contains an initial screening (using non invasive and low cost tests)
      that allows discarding contraindications for donation (in both donor and
      recipient). In a second phase the assessment of the donor varies with donor
      characteristics. However, a test for renal function is mandatory besides imaging
      techniques (like angioTC), screening for transmissible diseases and a detailed
      evaluation for psychosocial aspects preferably made by professional. Moreover
      Spanish policy on living donation requires a report with information about the
      consent for donation developed by an independent board (ethics committee) besides
      the consent for donation given at the civil registry.

PMID- 21183964
TI  - [Immunologic study of the donor-receptor couple].
AB  - The objective of the study is to evaluate the risk of graft failure. The presence
      of donor specific alloantibodies and the HLA incompatibilities between donor and
      receptor must be identified. There are several methods to identify alloandibodies
      that has different sensitivity and different Prognostic Value. Some define a high
      risk of hyperacute rejection, others an increase in the risk to loss the graft in
      defined subgroups. First steps of the pretransplant study identify: a) HLA typing
      of the receptor and available donors; b) alloantibodies by Complement Dependent
      Cytotoxicity against Panel (PRA-CDC) and screening of alloantibodies against HLA
      by Solid Phase; c) in sensitized receptors it can be useful to identify
      acceptable incompatibilities using Single Antigen Solid Phase technique and to
      evaluate the &laquo;Virtual Crossmatch&raquo;. Pretransplant study (10 days): a)
      crossmatch by Citotoxicity (CM-CDC) between receptor and donor; b) crossmatch by
      Flow-Cytometry (FCCM) between receptor and donor specially indicated in the
      retransplant. Useful also to discard IgM auto-antibodies. Receptors
      desensitization: the necessity and success probability of desensitization should
      be evaluated before treatment. Post-Transplant Monitoring: identify
      alloantibodies for: a) the differential diagnostic of corticorresistant rejection
      episodes with humoral component, and b) as a marker of long term reduced graft
      survival probability in the long term. Final remarks: Evaluation should consider
      the allosensibilization history of the receptor. The cytotoxicity crossmatch
      indicates a high risk of hyperacute rejection and is considered a
      contraindication. The Flow Cytometry crossmatch indicates an increase in the
      probability to loss the graft in the first year that is low for first transplants
      (>10%) but higher for retransplantation (>30%). The virtual crossmatch by solid
      phase indicates an increase in the probability to have an antibody mediated
      rejection (from 5% to 55%) but did not contraindicate always the transplant.

PMID- 21183965
TI  - [Surgical aspects of living-donor kidney transplantation].
AB  - Laparoscopic living donor nephrectomy has shown less morbidity than the open
      approach, with less pain and analgesia requirements and allowing a quicker
      recovery and an earlier return to normal activity. Furthermore, many studies have
      shown equivalent results between both approaches in terms of graft functions and
      recipient complications. For these reasons, we can accept laparoscopic kidney
      living donor nephrectomy as the gold standard surgical technique in these
      patients. The implementation of this minimally invasive technique in most centers
      has led to an increase in the rate of this kind of organ procurement, due to its
      better acceptance by the donors. In order to decide which kidney is better to
      extract, it is mandatory to maintain the best kidney in the donor. In case equal
      conditions, it is advisable to perform left nephrectomy.

PMID- 21183966
TI  - [Immunosuppression for living donor renal allograft recipients].
AB  - Living donor kidney transplantation allows immunosuppression individualization
      based on clinical and immunological criteria. Living donor kidney transplantation
      allows administration of immunosuppressive drugs days before transplantation, for
      a better acute rejection prevention. A 3-day course of tacrolimus and a
      micophenolic acid derivative is recommended. In recipients HLA-identical related
      to the donor, a tacrolimus-micophenolic acid r&eacute;gimen is recommended.
      Tacrolimus withdrawal after 6 months may be advisable. In all non-HLA-identical
      recipients, basiliximab induction is recommended, with the exception of high
      immunological risk patients, in whom thymoglobulin is a better option. The use of
      a kidney from an expanded criteria donor might imply a reduction in tacrolimus
      exposure since the very beginning, to optimize kidney graft function. In general,
      and depending on immunological risk, steroid withdrawal after the first 3 to 6
      months is recommended. ABO-incompatible living donor kidney transplantation is
      feasible after specific immunoadsorption, gammaglobulins, a dose of rituximab and
      conventional immunosupression.

PMID- 21183967
TI  - [Children as receptors of living donors].
AB  - The most important factor in life expectancy for children on renal replacement
      therapy (RRT) is to have a functioning graft when they reach adulthood (63 years 
      on transplantation vs 37 years on dialysis). The pediatric recipient is very
      suitable for a living donor transplantation (LDT), with few contraindications.
      There are several reasons that make LDT the most recommended RRT in children: pre
      emptive transplant avoiding dialysis, good renal mass, minimal cold ischemia
      time, better HLA-matching and the possibility to program the time of surgery.
      Long term graft survival in LDT is significantly better than in cadaveric donor
      transplantation (CDT) (81.3%  LDT vs 60.8 % CDT at 10 years follow-up).
      Calculated half-life graft survival for recipients aged 2-5 years reaches 27.5
      years in some series, making LDT the ideal option for these children. Adolescent
      recipients (12-17 years) have an excellent early graft survival, but the worst
      long term outcome compared with the rest of pediatric population. However,
      preemptive LDT has a 70% of graft survival at 10 years. Late rejections episodes
      associated with non-adherence factors are found in all series. Unrelated LDT in
      pediatric recipients outcome remain unclear.

PMID- 21183968
TI  - [Incompatible living donors in kidney tranplantation].
AB  - Renal transplant is the best option of treatment of chronic kidney disease and
      the shortage of cadaveric donors has caused the rapid increase of living donor
      programs. Provided that an important proportion of the donor-recipient pairs are
      incompatible between them, ABO incompatibility or positive cross-match test, one
      of the most important challenges of last decade, has been the solution of the
      above mentioned problem. For it there have begun the crossed-over transplant
      programs (also called donors' exchange programs) in his different combinations
      and these kind of transplants has been consolidated by an excellent results. To
      eliminate the titles of anti-HLA antibodies and the isoaglutinines we have
      different resources, beeing the most importants plasmapheresis, the
      immunoadsortion, immunoglobulin infusion, Rituximab use and splenectomy. They
      need all of them of the concomitant use of a powerful immunosuppression and of a
      suitable antiinfectious prevention. The results obtained with the incompatible
      donors are nowadays excellent and totally comparable to the obtained ones using
      living compatible donors.  

PMID- 21183969
TI  - [Short, medium and long-term follow-up of living donors].
AB  - Live-donor kidney transplants are being done since more than fifty years ago. In
      recent years, a marked increase in live donations is observed, as a result of the
      limited availability of organs from deceased donors. Also, the use of
      laparoscopic nephrectomy has contributed to increase live donations. A systematic
      review of the literature shows that short and long-term risks of morbidity and
      mortality of the donor are reasonably low. Even so, an increased incidence of
      high blood pressure and mild proteinuria has been reported. On the contrary, no
      detrimental effect on renal failure is observed and the incidence of long-term
      chronic renal failure is lower in the donor population when compared with the
      incidence observed in the general population. In any case, a regular follow-up of
      the donors is advisable in order to prevent or early detect those medical
      conditions that would represent a health risk, in particular those conditions
      that possibly will affect renal function: hypertension, diabetes, proteinuria and
      obesity. It would be also necessary to establish a nation-wide scientific
      registry, with prospective regular data collection, that will make possible a
      more accurate assessment of the long-term risk of uninephrectomy and early
      detection of new medical information that would contribute to redefine the risk
      of kidney donation or to establish new requisites in the donor evaluation
      protocols.

PMID- 21183970
TI  - Preparation of luminescent and mesoporous Eu3+/Tb3+ doped calcium silicate
      microspheres as drug carriers via a template route.
AB  - Luminescent and mesoporous Eu(3+)/Tb(3+) doped calcium silicate microspheres
      (LMCS) were synthesized by using mesoporous silica spheres as the templates. The
      LMCS and drug-loaded samples were characterized by means of X-ray diffraction
      (XRD), field emission scanning electron microscopy (FE-SEM), transmission
      electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), N(2)
      adsorption/desorption, and photoluminescence (PL) spectra. The results reveal
      that the LMCS have uniform spherical morphology with a diameter around 400 nm and
      the mesopore size of 6 nm. The prepared samples exhibit little cytotoxicity at
      concentrations below 5 mg mL(-1) via MTT assay. In addition, drug storage/release
      properties of the LMCS were demonstrated for ibuprofen (IBU). The obtained LMCS
      can be used to encapsulate drugs and release them. Under excitation by UV light,
      the IBU-loaded samples still show the characteristic (5)D(0)-(7)F(1-3) emission
      lines of Eu(3+) and the characteristic (5)D(4)-(7)F(3-6) emission lines of
      Tb(3+). The PL intensity of Eu(3+) in the drug carrier system increases with the
      cumulative released amount of IBU, making the drug release able to be tracked or
      monitored by the change of luminescence of Eu(3+). The LMCS reported here with
      mesoporous structure, good biocompatibility and luminescent property can be a
      promising drug delivery carrier.

PMID- 21183972
TI  - Red blood cell rheology using single controlled laser-induced cavitation bubbles.
AB  - The deformability of red blood cells (RBCs) is an important property that allows
      the cells to squeeze through small capillary vessels and can be used as an
      indicator for disease. We present a microfluidic based technique to quantify the
      deformability of RBCs by stretching a collection of RBCs on a timescale of tens
      of microseconds in a microfluidic chamber. This confinement constrains the motion
      of the cell to the imaging plane of the microscope during a transient cavitation
      bubble event generated with a focused and pulsed laser. We record and analyze the
      shape recovery of the cells with a high-speed camera and obtain a power law in
      time, consistent with other dynamic rheological results of RBCs. The extracted
      exponents are used to characterize the elastic properties of the cells. We obtain
      statistically significant differences of the exponents between populations of
      untreated RBCs and RBCs treated with two different reagents: neuraminidase
      reduces the cell rigidity, while wheat germ agglutinin stiffens the cell
      confirming previous experiments. This cavitation based technique is a candidate
      for high-throughput screening of elastic cell properties because many cells can
      be probed simultaneously in situ, thus with no pre-treatment.

PMID- 21183971
TI  - Imaging in real-time with FRET the redox response of tumorigenic cells to
      glutathione perturbations in a microscale flow.
AB  - Despite the potential benefits of selective redox-modulating strategies for
      cancer therapy, an efficacious methodology for testing therapies remains elusive
      because of the difficulty in measuring intracellular redox potentials over time.
      In this report, we have incorporated a new FRET-based biosensor to follow in real
      time redox-sensitive processes in cells transformed to be tumorigenic and
      cultured in a microfluidic channel. A microfluidic network was used to control
      micro-scale flow near the cells and at the same time deliver drugs exogenously.
      Subsequently, the response of a redox homeostasis circuit was tested, namely
      reduced glutathione (GSH)/oxidized glutathione(GSSG), to diamide, a thiol
      oxidant, and two drugs used for cancer therapies: BSO (L-buthionine-[SR]
      sulfoximine) and BCNU (carmustine). The main outcome from these experiments is a
      comparison of the temporal depletion and recovery of GSH in single living cells
      in real-time. These data demonstrate that mammalian cells are capable of
      restoring a reduced intracellular redox environment in minutes after an acute
      oxidative insult is removed. This recovery is significantly delayed by (i) the
      inhibition of GSH biosynthesis by BSO; (ii) the inactivation of glutathione
      reductase by BCNU; and (iii) in tumorigenic cells relative to an isogenic non
      tumorigenic control cell line.

PMID- 21183973
TI  - Alteration of microRNA expression correlates to fatty acid-mediated insulin
      resistance in mouse myoblasts.
AB  - As new regulators at the post-transcriptional level, microRNAs (miRNAs) are non
      coding 19-22 nucleotide RNA molecules that are believed to regulate the
      expression of thousands of genes. Since the monounsaturated fatty acid oleate can
      reverse insulin resistance induced by the saturated fatty acid palmitate, we
      carried out microarray analysis to determine differences in miRNA expression
      profiles in mouse muscle C2C12 cells that were treated with palmitate and
      palmitate plus oleate. Among the altered miRNAs, the expression levels of miR-7a,
      miR-194, miR-337-3p, miR-361, miR-466i, miR-706 and miR-711 were up- or down
      regulated by palmitate, but restored to their original level by oleate. These
      results were verified by quantitative RT-PCR (QRT-PCR). Further studies showed
      that over-expression of miR-7 down-regulated insulin receptor substrate 1 (IRS1)
      expression as well as inhibited insulin-stimulated Akt phosphorylation and
      glucose uptake. The miRNA expression profiles correlated to oleate protection
      against palmitate-induced insulin resistance in mouse muscle cells offer an
      alternative understanding of the molecular mechanism of insulin resistance.

PMID- 21183974
TI  - Thermal FT-IR microspectroscopy for rapid detection of solid-state ion-exchange
      reaction between metoclopramide HCl monohydrate and potassium bromide.
AB  - The combination of Fourier transform infrared (FT-IR) microspectroscopy with a
      thermal analyzer was applied to quickly investigate the solid-state ion-exchange
      reaction of metoclopramide HCl monohydrate (MCP H(2)O) by clipping MCP H(2)O
      powder between two KBr or KCl pellets. The physical and ground mixtures of MCP
      H(2)O or 150  degrees C-preheated MCP powder and KBr or KCl powders with a weight
      ratio of 1 : 100 were also prepared and determined by FT-IR microspectroscopy.
      The samples of MCP H(2)O or 150  degrees C-preheated MCP were identified by using
      differential scanning calorimetry (DSC) and thermogravimetric (TG) analysis. The
      results of present study indicate that the ion-exchange reaction was easily
      induced between MCP H(2)O and KBr by grinding and heating processes. The possible
      mechanism of ion-exchange reaction may take place between the HCl salt of MCP
      H(2)O and a KBr matrix by grinding or heating to yield a mixture of HCl and HBr
      salts of the MCP sample in the presence of hydrated water. The crystal hydrate
      played an important role to improve this ion-exchange reaction between MCP H(2)O
      and KBr. However, no ion-exchange reaction occurred between MCP H(2)O and KCl or
      between 150  degrees C-preheated MCP and KBr. The solid-state ion-exchange
      reaction was more easily determined by this novel thermal FT-IR microspectroscopy
      than other conventional methods.

PMID- 21183975
TI  - Functionalised endohedral fullerenes in single-walled carbon nanotubes.
AB  - Atomically thin carbon nanotubes serve as transparent-test tubes for individual
      molecules of functionalised endohedral fullerenes. Aberration-corrected
      transmission electron microscopy reveals the complex dynamic behaviour of these
      molecules at the atomic level, and it sheds light on the mechanism of their
      encapsulation into nanotubes.

PMID- 21183976
TI  - Monoolein: a magic lipid?
AB  - During the last few years, there has been an extraordinary increase in
      publications describing the manifold applications of monoolein, one of the most
      important lipids in the fields of drug delivery, emulsion stabilization and
      protein crystallization. In this perspective we present a comprehensive review of
      the phase behavior of this 'magic lipid'. An account of various mesophases formed
      in the presence of water and a collection of formulae for the calculation of
      their nano-structural parameters are provided. Effects of chemical and biological
      molecules including lipids, detergents, salts, sugars, proteins and DNA on the
      classical behavior are also discussed. Physicochemical triggers such as,
      temperature, pressure and shearing modulate the phase behavior of monoolein self
      assemblies that are covered in subsequent sections. Finally the growing
      applications of monoolein in various fields are also reported.

PMID- 21183977
TI  - Substituents dependent capability of bis(ruthenium-dioxolene-terpyridine)
      complexes toward water oxidation.
AB  - The bridging ligand, 1,8-bis(2,2':6',2''-terpyrid-4'-yl)anthracene (btpyan) was
      synthesized by the Miyaura-Suzuki cross coupling reaction of anthracenyl-1,8
      diboronic acid and 4'-triflyl-2,2':6'-2''-terpyridine in the presence of
      Pd(PPh(3))(4) (5 mol%) with 68% in yield. Three ruthenium-dioxolene dimers,
      [Ru(2)(OH)(2)(dioxolene)(2)(btpyan)](0) (dioxolene = 3,6-di-tert-butyl-1,2
      benzosemiquinone ([1](0)), 3,5-dichloro-1,2-benzosemiquinone ([2](0)) and 4-nitro
      1,2-benzosemiquinone ([3](0))) were prepared by the reaction of
      [Ru(2)Cl(6)(btpyan)](0) with the corresponding catechol. The electronic structure
      of [1](0) is approximated by [Ru(II)(2)(OH)(2)(sq)(2)(btpyan)](0) (sq =
      semiquinonato). On the other hand, the electronic states of [2](0) and [3](0) are
      close to [Ru(III)(2)(OH)(2) (cat)(2)(btpyan)](0) (cat = catecholato), indicating
      that a dioxolene having electron-withdrawing groups stabilizes
      [Ru(III)(2)(OH)(2)(cat)(2)(btpyan)](0) rather than
      [Ru(II)(2)(OH)(2)(sq)(2)(btpyan)](0) as resonance isomers. No sign was found of
      deprotonation of the hydroxo groups of [1](0), whereas [2](0) and [3](0) showed
      an acid-base equilibrium in treatments with t-BuOLi followed by HClO(4).
      Furthermore, controlled potential electrolysis of [1](0) deposited on an ITO
      (indium-tin oxide) electrode catalyzed the four-electron oxidation of H(2)O to
      evolve O(2) at potentials more positive than +1.6 V (vs. SCE) at pH 4.0. On the
      other hand, the electrolysis of [2](0) and [3](0) deposited on ITO electrodes did
      not show catalytic activity for water oxidation under similar conditions. Such a
      difference in the reactivity among [1](0), [2](0) and [3](0) is ascribed to the
      shift of the resonance equilibrium between [Ru(II)(2)(OH)(2)(sq)(2)(btpyan)](0)
      and [Ru(III)(2)(OH)(2)(cat)(2)(btpyan)](0).

PMID- 21183978
TI  - Assessment of the LiX salt-effect in anthracenyl lithiums.
AB  - Based on lithium anthracenes RLi, the formation of mixed complexes from
      organolithiums and lithium salts RLi.LiX is illustrated. The [RLi(L)](2) dimers
      formed in presence of different donating solvents L as well as the corresponding
      mixed lithium bromide complexes [RLi(L).LiX] were isolated and structurally
      characterized.

PMID- 21183979
TI  - Low-temperature dynamics in amorphous polymers and low-molecular-weight glasses-
      what is the difference?
AB  - Numerous experiments have shown that the low-temperature dynamics of a wide
      variety of disordered solids is qualitatively universal. However, most of these
      results were obtained with ensemble-averaging techniques which hide the local
      parameters of the dynamic processes. We used single-molecule (SM) spectroscopy
      for direct observation of the dynamic processes in disordered solids with
      different internal structure and chemical composition. The surprising result is
      that the dynamics of low-molecular-weight glasses and short-chain polymers does
      not follow, on a microscopic level, the current concept of low-temperature glass
      dynamics. An extra contribution to the dynamics was detected causing
      irreproducible jumps and drifts of the SM spectra on timescales between
      milliseconds and minutes. In most matrices consisting of small molecules and
      oligomers, the spectral dynamics was so fast that SM spectra could hardly or not
      at all be recorded and only irregular fluorescence flares were observed. These
      results provide new mechanistic insight into the behavior of glasses in general:
      At low temperatures, the local dynamics of disordered solids is not universal but
      depends on the structure and chemical composition of the material.

PMID- 21183980
TI  - Ion conducting particle networks in liquids: modeling of network percolation and
      stability.
AB  - Networks of inorganic particles (here SiO(2)) formed within organic liquids play
      an important role in science. Recently they have been considered as 'soggy sand'
      electrolytes for Li-based batteries with a fascinating combination of mechanical
      and electrical properties. In this communication we model formation and stability
      of the networks by Cluster-Cluster Aggregation followed by coarsening on a
      different time scale. The comparison of computer simulations based on our model
      with experimental results obtained for LiClO(4) containing polyethylene glycol
      reveals (i) that the percolation threshold for interfacial conductivity is very
      small, (ii) that the networks once formed coarsen with a time constant that is
      roughly independent of volume fraction and size--to a denser aggregate which then
      stays stable under operating condition. (iii) Trapping of the conducting solvent
      at high packing is also revealed.

PMID- 21183981
TI  - Temperature dependent single molecule rotational dynamics in PMA.
AB  - Temperature dependent measurements of the rotational diffusion of single dye
      molecules in the polymer poly(methyl acrylate) (PMA) are presented and compared
      to shear viscosity data and numerical simulations of the rotational diffusion
      process. It is found that single molecule rotational diffusion very accurately
      follows the Debye-Stokes-Einstein predictions for the shear viscosity without any
      additional parameter. We employ a simple model of dynamic changes of the
      rotational speed of a single molecule. This dynamic heterogeneity model is based
      on a Gaussian distribution of activation energies in a VFTH (Vogel-Fulcher
      Tammann-Hesse) type temperature dependence of the polymer viscosity. The
      simulations explain all experimental details concerning the stretched exponential
      single molecule relaxation dynamics and the related distributions. They also
      reveal that the observed distributions are related to the intrinsic physical
      properties of the polymer but do not in general reflect the instantaneous spread
      of local viscous properties.

PMID- 21183982
TI  - A light-powered stretch-contraction supramolecular system based on cobalt
      coordinated [1]rotaxane.
AB  - A mechanically switchable bistable [1]rotaxane, constituted of azobenzene
      modified cyclodextrins (CyDs) and a Schiff base bridged by a metallosalen unit,
      was designed and synthesized. (1)H NOESY NMR and ICD spectra were investigated to
      characterize the movement process of this stretch-contraction supramolecular
      system. The geometries of [1]rotaxane before and after irradiation by UV light
      were optimized and calculated. Coordinated with cobalt(III) ion, the rotaxane
      becomes more rigid and linear, which is seen from the more obvious signals in the
      induced circular dichroism (ICD) and (1)H NMR spectra. This type of light-powered
      [1]rotaxane has favourable repeatability and exhibits a novel approach to
      elaborate the transformation of a light-driven molecular machine.

PMID- 21183983
TI  - Pressure-induced collapse of guanidinium nitrate N-H...O bonded honeycomb layers
      into a 3-D pattern with varied H-acceptor capacity.
AB  - Highly favoured N-H...O bonded honeycomb layers in guanidinium nitrate,
      C(NH(2))(3)(+)NO(3)(-), have been destabilized by a pressure of 0.6 GPa, and the
      novel motif of 3-dimensional N-H...O bonded aggregation in high-pressure phase IV
      determined for in situ grown single-crystal by X-ray diffraction. The mechanism
      of the transition involves the collapse of voids present in phases I, II and III.
      In the P/T phase diagram a large hysteresis of the phase IV boundaries is caused
      by the strongly reconstructive character of the transition and pressure dependent
      H-accepting capacity of oxygen atoms.

PMID- 21183984
TI  - Enhanced luminescence of europium-doped layered double hydroxides intercalated by
      sensitiser anions.
AB  - Four sensitising anions naphthalene-1,5-disulfonate (15-NDS), naphthalene-2,6
      dicarboxylate (26-NDC), benzoate (BA) and terephthalate (TA) were intercalated
      into a Eu(3+)-doped Zn/Al layered double hydroxide. The carboxylate anions
      enhanced the red luminescence of Eu(3+) much more strongly than the sulfonate, in
      the descending order TA > 26-NDC > BA > 15-NDS.

PMID- 21183985
TI  - Gold catalyzes the Sonogashira coupling reaction without the requirement of
      palladium impurities.
AB  - By a combination of kinetic and theoretical studies it is concluded that gold is
      intrinsically active to perform the Sonogashira coupling reaction between
      phenylacetylene and iodobenzene. The presence of Pd impurities is not mandatory
      for catalyst activity.

PMID- 21183986
TI  - Macromolecular dynamics of conjugated polymer in donor-acceptor blends with
      charge transfer complex.
AB  - Donor-acceptor blends based on conjugated polymers are the heart of state-of-the
      art polymer solar cells, and the control of the blend morphology is crucial for
      their efficiency. As the film morphology can inherit the polymer conformational
      state from solution, the approaches for probing and controlling the polymer
      conformational state in the blends are of high importance. In this study, we show
      that the macromolecular dynamics in solutions of the archetypical conjugated
      polymer, MEH-PPV, is essentially changed upon addition of an acceptor 2,4,7
      trinitrofluorenone (TNF) by using dynamic light scattering (DLS). We have
      observed four new types of the macromolecular dynamics absent in the parent
      polymer determined by the polymer and acceptor content. The MEH-PPV : TNF ground
      state charge-transfer complex (CTC) is suggested to result in these dynamics. In
      the dilute polymer solution, the CTC formation leads to slower dynamics as
      compared with the pristine polymer. This is evidence of aggregates formed by
      intercoil links that are the CTCs involving two conjugated segments of different
      coils with acceptor molecules being sandwiched between them. At low acceptor
      content, the aggregates are not stable but at high acceptor content, they are. In
      the semidilute solution at low acceptor content, the dynamics becomes faster as
      compared with the pristine polymer that is explained by confinement of the
      coupled motions of entangled polymer chains. At high acceptor content, the
      dynamics is far much slower with a characteristic long-range correlation at the
      scale 3-5 MUm that is explained by aggregation of polymer chains in clusters. One
      can expect that the DLS technique could become a useful tool to study the nano-
      and microstructure of donor-acceptor conjugated polymer blends to achieve
      controllable morphology in the corresponding blend films.

PMID- 21183987
TI  - Rh(1-x)Pd(x) nanoparticle composition dependence in CO oxidation by oxygen:
      catalytic activity enhancement in bimetallic systems.
AB  - Bimetallic 15 nm Rh(1-x)Pd(x) nanoparticle catalysts of five different
      compositions and supported on Si wafers have been synthesized, characterized
      using TEM, SEM, and XPS, and studied in CO oxidation by O(2) in two pressure
      regimes: atmospheric pressure and 100-200 mTorr. The RhPd bimetallic nanocrystals
      exhibited similar synergetic effect of increased reaction activity at both
      atmospheric (760 Torr) and moderate (100-200 mTorr) pressures compared with pure
      Pd or Rh. The magnitude of the effect depends on the relative pressures of the CO
      and O(2) reactant gases and the reaction temperature. The catalytic activity of
      the nanocrystals measured at moderate pressure is directly correlated to the
      APXPS studies, which were carried out in the same pressure. The APXPS studies
      suggest that the Pd-Rh interfaces are important for the enhanced activity of the
      bimetallic nanoparticles.

PMID- 21183988
TI  - Seeing the forest for the trees: fluorescence studies of single enzymes in the
      context of ensemble experiments.
AB  - Enzymes are remarkable molecular machines that make many difficult biochemical
      reactions possible under mild biological conditions with incredible precision and
      efficiency. Our understanding of the working principles of enzymes, however, has
      not reached the level where one can readily deduce the mechanism and the
      catalytic rates from an enzyme's structure. Resolving the dynamics that relate
      the three-dimensional structure of an enzyme to its function has been identified
      as a key issue. While still challenging to implement, single-molecule techniques
      have emerged as one of the most useful methods for studying enzymes. We review
      enzymes studied using single-molecule fluorescent methods but placing them in the
      context of results from other complementary experimental work done on bulk
      samples. This review primarily covers three enzyme systems--flavoenzymes,
      dehydrofolate reductase, and adenylate kinase--with additional enzymes mentioned
      where appropriate. When the single-molecule experiments are discussed together
      with other methods aiming at the same scientific question, the weakness,
      strength, and unique contributions become clear.

PMID- 21183989
TI  - Binary [Cu2O/MWCNT] and ternary [Cu2O/ZnO/MWCNT] nanocomposites: formation,
      characterization and catalytic performance in partial ethanol oxidation.
AB  - Cuprous oxide agglomerates composed of 4-10 nm Cu2O nanoparticles were deposited
      on multiwalled carbon nanotubes (MWCNTs) and on ZnO/MWCNTs to give binary
      [Cu2O/MWCNT] and ternary [Cu2O/ZnO/MWCNT] composites. Di-aqua-bis[2
      (methoxyimino)propanoato]copper Cu[O2CCCH3NOMe](2).2H2O 1 in DMF was used as
      single source precursor for the deposition of nanoscaled Cu2O. The precursor
      decomposes either in air or under argon to yield CuO2 by in situ redox reaction.
      Thermogravimetric coupled mass spectroscopic analysis (TG-MS) of 1 revealed that
      methanol formed during the decomposition of 1 acts as a potential in situ
      reducing agent. Scanning electron microscopy (SEM) of the binary [Cu2O/MWCNT]
      nano-composite shows an increase of cuprous oxide loading depending on the
      precursor amount, along the periphery of the MWCNTs as well as formation of
      larger particle agglomerates. Transmission electron microscopy (TEM) of the
      sample shows crystalline domains of size 4-10 nm surrounded by an amorphous
      region within the larger particles. SEM and TEM of ternary [Cu2O/ZnO/MWCNT]
      clearly reveal that Cu2O nanoparticles are primarily deposited on ZnO rather than
      on MWCNTs. The catalytic activities of the [Cu2O/MWCNT] and [Cu2O/ZnO/MWCNT]
      binary and ternary composites were studied for the selective partial oxidation of
      ethanol to acetaldehyde with molecular oxygen. While using binary [Cu2O/MWCNT]
      (13.8 wt% Cu) as catalyst, acetaldehyde was obtained with a yield of 87% at 355 
      degrees C (selectivity 96% and conversion 91%). When nanoscale ZnO is present,
      the resulting [Cu2O/ZnO/MWCNT] composite shows preferential hydrogen and CO2
      formation due to the fact that the dehydrogenation and total oxidation pathway is
      more favoured compared to the binary composite. Significant morphological changes
      of the catalyst during the catalytic process were observed.

PMID- 21183990
TI  - Hydrophilic mesoporous carbon nanoparticles as carriers for sustained release of
      hydrophobic anti-cancer drugs.
AB  - The uniform mesoporous carbon nanoparticles (MCNs) with size below 200 nm and
      good water dispersibility were successfully synthesized via a combined
      hydrothermal synthesis and hard templating. The prepared MCNs served as effective
      carriers for camptothecin which efficiently inhibited the growth of MCF-7 cancer
      cells after its sustained release therein.

PMID- 21183991
TI  - Long signal peptides of RGMa and DCBLD2 are dissectible into subdomains according
      to the NtraC model.
AB  - Targeting of proteins to the endoplasmic reticulum (ER) usually requires N
      terminal signal peptides (SP) of approximately 22 amino acids in length. However,
      a substantial number of proteins contain exceptionally long SPs of 40 amino acids
      and more, an example being protein shrew-1/AJAP1. Using shrew-1's SP as example,
      the NtraC model has been developed by dissecting long SPs into two functionally
      distinct subdomains ("N" and "C") separated by a beta-turn rich transition area
      ("tra"). Further proteins have been identified by computational analysis
      complying with the NtraC model. Here we used the SPs of two of these proteins,
      DCBLD2 and RGMa (including three isoforms), to show that the NtraC model applies
      to a growing group of SPs. We demonstrate that the full-length SPs of RGMa and
      DCBLD2 are functional and furthermore that the C-domains are sufficient and
      essential for ER targeting, whereas the N-domains are dispensable. Thus, the N
      domains are available for additional functions.

PMID- 21183992
TI  - Anion tuning and polymer templating in a simple low molecular weight
      organogelator.
AB  - A simple triethoxysilane appended bis(urea) low molecular weight gelator (LMWG)
      affords strong gels in organic solvents that are susceptible to fine tuning by
      anion binding, while the gel structure can be rigidified into a porous hybrid
      polymer material by hydrolysis of the triethoxysilane end groups.

PMID- 21183993
TI  - Anisotropic multicompartment micro- and nano-capsules produced via embedding into
      biocompatible PLL/HA films.
AB  - We present a novel strategy to fabricate anisotropic multicompartment Janus
      capsules by embedding larger containers into a soft poly-L-lysine/hyaluronic acid
      (PLL/HA) polymeric film, followed by adsorption of smaller containers on top of
      their unmasked surface. This research is also attractive for developing
      substrates for cell cultures.

PMID- 21183994
TI  - Regioselective lactonization of unsymmetrical 1,4-diols: an efficient access to
      lactone lignans.
AB  - A Cp*Ru-based bifunctional catalyst system (Cp* = eta(5)-C(5)(CH(3))(5)) with a
      suitably-designed PN ligand (PN = chelating tertiary phosphine-protic amine
      ligand) has been developed for a regioselective lactonization of unsymmetrically
      substituted 1,4-diols, which may provide an expeditious access to a variety of
      lactone lignans.

PMID- 21183995
TI  - A shock tube and theoretical study on the pyrolysis of 1,4-dioxane.
AB  - The dissociation of 1, 2 and 4% 1,4-dioxane dilute in krypton was studied in a
      shock tube using laser schlieren densitometry, LS, for 1550-2100 K with 56 +/- 4
      and 123 +/- 3 Torr. Products were identified by time-of-flight mass spectrometry,
      TOF-MS. 1,4-dioxane was found to initially dissociate via C-O bond fission
      followed by nearly equal contributions from pathways involving 2,6 H-atom
      transfers to either the O or C atom at the scission site. The 'linear' species
      thus formed (ethylene glycol vinyl ether and 2-ethoxyacetaldehyde) then
      dissociate by central fission at rates too fast to resolve. The radicals produced
      in this fission break down further to generate H, CH(3) and OH, driving a chain
      decomposition and subsequent exothermic recombination. High-level ab initio
      calculations were used to develop a potential energy surface for the
      dissociation. These results were incorporated into an 83 reaction mechanism used
      to simulate the LS profiles with excellent agreement. Simulations of the TOF-MS
      experiments were also performed with good agreement for consumption of 1,4
      dioxane. Rate coefficients for the overall initial dissociation yielded
      k(123Torr) = (1.58 +/- 0.50) * 10(59) * T(-13.63) * exp(-43970/T) s(-1) and
      k(58Torr) = (3.16 +/- 1.10) * 10(79) * T(-19.13) * exp(-51326/T) s(-1) for 1600 <
      T < 2100 K.

PMID- 21184000
TI  - Anion-correlated conduction band edge shifts and charge transfer kinetics in dye
      sensitized solar cells with ionic liquid electrolytes.
AB  - In solvent-free ionic liquid electrolytes for efficient dye-sensitized solar
      cells, iodide and non-iodide melts are ordinarily blended in order to attain a
      high dynamic fluidity and thereby meet a fast mass transport of electroactive
      species. This common tactic could bring forth a prominent impact of various
      anions on cell efficiency by altering photocurrent and/or photovoltage. Herein we
      report evident effects of the dicyanamide versus tetracyanoborate anion on the
      energetics of titania conduction band edge and the kinetics of multi-channel
      charge-transfer reactions in cells employing a high absorption coefficient
      ruthenium sensitizer C106. A slightly shorter photoluminescence lifetime of C106
      grafted on alumina is probed for the tetracyanoborate-based reference cell with
      respect to the dicyanamide counterpart. However, owing to a more favourable
      thermodynamic driving force of ~90 meV, the tetracyanoborate anion prompts an
      almost 3-fold faster electron injection from the excited-state dye to titania
      than dicyanamide, leading to a higher charge separation yield, which is in good
      agreement with an almost indistinguishable ratio of external quantum efficiency
      enhancement in the whole spectral response region. Compared to tetracyanoborate,
      the presence of dicyanamide at the titania/electrolyte interface evokes a 27-fold
      smaller interfacial electron exchange rate (K) with triiodide, accounting for the
      open-circuit photovoltage variation observed in current-voltage measurements.

PMID- 21183996
TI  - Investigating excited state dynamics of salinixanthin and xanthorhodopsin in the
      near-infrared.
AB  - Excited state dynamics of native Xanthorhodopsin (XR), of an XR sample with a
      reduced prosthetic group, and of the associated Carotenoid (CAR) salinixanthin
      (SX) in ethanol were investigated by hyperspectral Near Infrared (NIR) probing.
      Global kinetic analysis shows that: (1) unlike the transient spectra recorded in
      the visible, fitting of the NIR data requires only two phases of exponential
      spectral evolution, assigned to internal conversion from S(2) -> S(1) and from
      S(1) -> S(0) of the carotene. (2) The rate of the internal conversion from S(2) 
      > S(1) in the reduced sample is well fit with a decay time of 130 fs,
      significantly longer than in XR and in SX, both of which are well fit with tau ~
      100 fs. This increased lifetime is consistent with a ~30% efficiency of ET from
      SX to retinal in XR. (3) S(1) of salinixanthin is verified to lie ~12,700 cm(-1)
      above the ground electronic surface, excluding its involvement in the retinal
      sensitization in XR. (4) The oscillator strength of the S(1) -> S(2) transition
      is determined to be no more than 0.16, despite its symmetry allowedness. (5) No
      long lived NIR absorbance decay assignable to the carotenoid S* state was
      detected in any of the samples. Inconsistencies concerning previously determined
      S(2) lifetimes and kinetic schemes used to model these data are discussed.

PMID- 21184001
TI  - Littoral diatoms as indicators of recent water and sediment contamination by
      metals in lakes.
AB  - We studied the response of benthic diatoms to recent metal contamination in
      littoral cores collected at 25 sites in 11 lakes situated at different distances
      from a smelter in the Rouyn-Noranda mining region (Quebec). Diatom response was
      described in terms of density, diversity, and taxonomic composition of the entire
      assemblages and as abundance of individual indicator taxa. Metal concentrations
      were measured in sediment and in the overlying water (as total dissolved and as
      free-ions). Sediment metal contamination was significantly higher in lakes
      located <10 km from the smelters than in lakes farther away. Such difference was
      not significant when metal concentrations in the overlying water were considered.
      Metal contamination did not affect diatom density, which indeed was highest in
      the most contaminated lake. Diversity (either measured as number of taxa or as
      Shannon and evenness indices) was instead significantly higher in lakes close to
      the smelter than elsewhere. Redundancy analysis indicated that diatom composition
      changed along a gradient in alkalinity (CO3) and one in sediment metal
      contamination (Cd, Hg, Cu). We identified three diatom taxa (Fragilaria
      construens var. venter, F. construens var. pumila, and Brachysira vitrea) that
      increased in relative and absolute abundance with metal contamination. Benthic
      diatom responses at the community (density, diversity, assemblage composition)
      and population levels (abundance of selected benthic taxa) were stronger to the
      sediment metal contamination than to the contamination of overlying water.
      Comparisons with available literature indicated that, for monitoring recent
      sediment contamination, diatoms in littoral sediments are preferable to
      invertebrates that mostly respond to overlying water. Diatoms in littoral cores
      are therefore unique as tools for monitoring recent contamination of lake
      sediments.

PMID- 21184002
TI  - Toxic and essential elements in blood from delivering women in selected areas of
      Sao Paulo State, Brazil.
AB  - This study was designed to evaluate the degree of environmental contamination and
      possible exposure of pregnant women to toxic elements in seven selected areas of
      Sao Paulo State, Brazil. The overall median concentration of Mo in maternal blood
      was 0.53 MUg L-1, highly significant differences found between sites (p <
      0.0001). Cd was found to be low overall - 0.09 MUg L-1 (0.01-0.58 MUg L-1) - with
      mothers from the Coastal and Rural 1 sites having the highest levels (p <
      0.016).Median Hg concentration was 0.60 MUg L-1 (0.06 MUg L-1-4.35 MUg L-1);
      median Pb level was 16.2 MUg L-1 (3.5-57.7 MUg L-1) and no differences between
      sites were observed for both metals. Median Mn level was 16.7 MUg L-1 (7.0-39.7
      MUg L-1), being highest in Urban 2 site (p < 0.016). Concentrations of maternal
      Co were found to range between 0.06 MUg L-1 and 1.1 MUg L-1 (median 0.25 MUg L-1)
      and As level was 0.60 MUg L-1 (0.10-3.8 MUg L-1) overall, with no statistical
      significance between sites for Co and As. Median Se concentrations were found to
      be 64 MUg L-1 (36-233 MUg L-1), with the highest median levels found in Urban 3
      site; site differences were statistically significant (p < 0.0001). Correlation
      for each element (between paired maternal and cord blood) was measured only in
      Rural site 1; significant correlation was shown for Hg, Pb, Mn and Co (p < 0.05).
      These findings may be interpreted as indicating low environmental contamination
      in Sao Paulo State, Brazil. These findings could also indicate that pregnant
      women have little or no contact with pollutants, possibly due to awareness
      campaigns carried out by public health practitioners.

PMID- 21184004
TI  - Activity-guided engineering of natural product carrier proteins.
AB  - A panel of chimeric carrier proteins was developed and screened for functional
      activity with essential enzymes involved in carrier protein-mediated
      biosynthesis. Regions on either side of the recognition helix II within three
      carrier proteins (CPs) from distinct biosynthetic pathways were swapped in all
      combinations to generate 24 mutated CPs. This panel of chimeric carrier proteins
      was tested using two previously established and one novel carrier protein assays.
      The results suggest a significant contribution from multiple structural units
      within carrier protein structure, rather than universal recognition helix, is
      necessary for proper recognition and activity with partner enzymes.

PMID- 21184005
TI  - Mechanism-based affinity capture of sirtuins.
AB  - The ability to probe for catalytic activities of enzymes and to detect their
      abundance in complex biochemical contexts has traditionally relied on a
      combination of kinetic assays and techniques such as western blots that use
      expensive reagents such as antibodies. The ability to simultaneously detect
      activity and isolate a protein catalyst from a mixture is even more difficult and
      currently impossible in most cases. In this manuscript we describe a chemical
      approach that achieves this goal for a unique family of enzymes called sirtuins
      using novel chemical tools, enabling rapid detection of activity and isolation of
      these protein catalysts. Sirtuin deacetylases are implicated in the regulation of
      many physiological functions including energy metabolism, DNA-damage response,
      and cellular stress resistance. We synthesized an aminooxy-derivatized NAD(+) and
      a pan-sirtuin inhibitor that reacts on sirtuin active sites to form a chemically
      stable complex that can subsequently be crosslinked to an aldehyde-substituted
      biotin. Subsequent retrieval of the biotinylated sirtuin complexes on
      streptavidin beads followed by gel electrophoresis enabled simultaneous detection
      of active sirtuins, isolation and molecular weight determination. We show that
      these tools are cross reactive against a variety of human sirtuin isoforms
      including SIRT1, SIRT2, SIRT3, SIRT5, SIRT6 and can react with microbial derived
      sirtuins as well. Finally, we demonstrate the ability to simultaneously detect
      multiple sirtuin isoforms in reaction mixtures with this methodology,
      establishing proof of concept tools for chemical studies of sirtuins in complex
      biological samples.

PMID- 21184006
TI  - The stoichiometry of single nanoparticles of copper zinc tin selenide.
AB  - Cu(2)ZnSnSe(4) nanoparticles have high potential to be used as ink for printable
      solar cells. Using transmission electron microscopy we show that these
      nanoparticles exhibit a broad range of chemical heterogeneity. These results are
      contrary to the interpretation of previous experimental work and will have
      considerable impact on the development of these nanoparticles.

PMID- 21184007
TI  - One-step covalent grafting of Fe4 single-molecule magnet monolayers on gold.
AB  - Iron(III)-based single-molecule magnets have been covalently grafted on Au(111)
      in one step using 1,2-dithiolan-3-yl side groups. Reaction with the substrate
      quantitatively affords a monolayer of electronically intact clusters doubly
      linked to the surface via Au-S bonds, as demonstrated by a combination of STM,
      XAS/XMCD and XPS studies.

PMID- 21184003
TI  - An architectural genetic and epigenetic perspective.
AB  - The organization and intranuclear localization of nucleic acids and regulatory
      proteins contribute to both genetic and epigenetic parameters of biological
      control. Regulatory machinery in the cell nucleus is functionally
      compartmentalized in microenvironments (focally organized sites where regulatory
      factors reside) that provide threshold levels of factors required for
      transcription, replication, repair and cell survival. The common denominator for
      nuclear organization of regulatory machinery is that each component of control is
      architecturally configured and every component of control is embedded in
      architecturally organized networks that provide an infrastructure for integration
      and transduction of regulatory signals. It is realistic to anticipate emerging
      mechanisms that account for the organization and assembly of regulatory complexes
      within the cell nucleus can provide novel options for cancer diagnosis and
      therapy with maximal specificity, reduced toxicity and minimal off-target
      complications.

PMID- 21184009
TI  - Nb doping of TiO2 nanotubes for an enhanced efficiency of dye-sensitized solar
      cells.
AB  - Nb-doped TiO(2) nanotube (with C(Nb) < 1 wt%) layers were successfully fabricated
      by self-ordered electrochemical anodization of Ti-Nb alloys. When used in dye
      sensitized solar cells the efficiency enhanced by up to 30% compared to non-doped
      TiO(2) nanotubes. IMVS measurements indicate the beneficial effect to be due to
      lower recombination losses.

PMID- 21184010
TI  - Controllable preparation of nanoparticle-coated chitosan microspheres in a co
      axial microfluidic device.
AB  - In this work, we describe a novel and simple microfluidic method for fabricating
      nanoparticle-coated chitosan microspheres. Uniform droplets of aqueous chitosan
      solution were dispersed into an oil phase containing partially hydrophilic
      nanoparticles via a co-axial microfluidic device. Recirculating flow in the
      continuous phase in the area between drops enhanced mixing and allowed the
      nanoparticles to coat the surface of the droplets as they passed through the
      channel. The chitosan droplets were then crosslinked with glutaraldehyde and
      nanoparticle-coated microspheres were obtained. SEM characterization shows that
      the microspheres are monodispersed with uniform nanoparticle distribution on the
      surface. The dispersity, size and composition of the microspheres could all
      easily be controlled by changing the microfluidic flow parameters and three
      different types of nanoparticles were successfully used to synthesize hybrid
      microspheres to demonstrate the method's versatility.

PMID- 21184008
TI  - Highly efficient synthesis of cyclic carbonates from CO2 and epoxides over
      cellulose/KI.
AB  - Cellulose/KI is a very active, selective, stable, and recyclable catalyst for the
      cycloaddition reactions of CO(2) and epoxides due to the excellent synergetic
      effect of cellulose and KI. It is found that the hydroxyl groups on the vicinal
      carbons of cellulose play a key role for the very high efficiency of the
      catalyst.

PMID- 21184011
TI  - Treasures from the Free Radical Renaissance Period--miscellaneous hexenyl radical
      kinetic data.
AB  - Rate constant data and Arrhenius parameters have been determined for a series of
      substituted hexenyl radicals of differing electronic and steric demand. Electron
      withdrawing groups (CF(3), CO(2)Et) directly attached to the radical centre
      slightly accelerate 5-exo ring-closure (k(cis) + k(trans) ~ 2.1 * 10(5) s(-1) at
      25 degrees ) relative to donating groups (OMe; 1.6 * 10(5) s(-1) at 25 degrees ).
      Sterically demanding groups (tert-Bu), as expected, slow the cyclization process
      (1 * 10(5) s(-1)). These observations are consistent with subtle changes in
      activation energy for 5-exo ring-closure. Interestingly, the nature of the
      solvent would appear to have a significant influence on this chemistry with the
      cis/trans stereoselectivity sometimes improved as the solvent polarity is
      increased. Except for the system containing the CF(3) (electron-withdrawing)
      group which displays an increase in the cyclization/capture rate constant
      (k(c)/k(H)), a general decrease in the k(c)/k(H) ratio as solvent polarity is
      increased is noted; these changes have been speculated to arise mainly from
      changes in k(H) in the various solvents employed.

PMID- 21184012
TI  - Cold collisions of N (4S) atoms and NH (3Sigma) molecules in magnetic fields.
AB  - We calculate the interaction potential between N atoms and NH molecules and use
      it to investigate cold and ultracold collisions important for sympathetic
      cooling. The ratio of elastic to inelastic cross sections is large over a wide
      range of collision energy and magnetic field for most isotopic combinations, so
      that sympathetic cooling of NH molecules by N atoms is a good prospect. However,
      there are important effects due to a p-wave shape resonance that may inhibit
      cooling in some cases. We show that scaling the reduced mass used in the
      collision is approximately equivalent to scaling the interaction potential. We
      then explore the dependence of the scattering properties on the reduced mass and
      explain the resonant effects observed using angular-momentum-insensitive quantum
      defect theory.

PMID- 21184016
TI  - Development and evaluation of an allied health research training scheme.
AB  - Allied health professionals are increasingly encouraged to utilise clinical
      research skills within their practice. While undergraduate allied health courses
      include some training in basic research skills, little is known about the most
      effective methods of continuing research training into professional life. This
      paper describes the implementation and evaluation of a 12-week allied health
      research training program, targeting interested clinicians and utilising a mixed
      approach of group learning and individual mentoring to guide participants through
      the process of conducting a systematic review of the literature. Evaluation
      included a qualitative analysis of in-depth semi-structured interviews with the
      first cohort of participants who completed the program (n=6) and their mentors
      (n=6), a quantitative analysis of changes in research interest, experience, and
      confidence of those who enrolled in the program (n=7) using the Research Spider
      tool, and a 6-month follow-up of research outputs resulting from the program.
      Results indicated that the program was beneficial, although the time and new
      learning required was a challenge for both participants and mentors. A
      significant increase was observed in research confidence, as well as an observed
      improvement in research experience, that approached but did not achieve
      statistical significance (p=0.06). At 6-month follow-up, the program had led to
      the submission of three papers for publication and one conference presentation.
      The results of the evaluation indicate that a research training program targeting
      motivated and interested clinicians and utilising existing resources can lead to
      tangible outputs within a clinical setting.

PMID- 21184017
TI  - Patient readiness and ability to set recovery goals during the first 6 months
      after stroke.
AB  - Goal setting is recommended both in the acute and rehabilitation phases after
      stroke, yet this presents multiple challenges for patients and clinicians. The
      aim of this study was to describe the participants' readiness and ability to set
      goals over time. METHODS: Fifteen stroke survivors aged 18-70 yrs were
      interviewed using a semi-structured interview guide at three time points: on the
      acute stroke unit, while participating in a subacute rehabilitation program, and
      6 mos after the stroke. Content analysis was performed using NVivo. RESULTS:
      Participants had difficulty setting goals early after stroke. Contributing to
      this was limited understanding of goal terminology, wanting to "get back to
      normal," differences in readiness to set goals, and poor knowledge about typical
      stroke recovery. CONCLUSION: Future models need to acknowledge the importance of
      timing and education in goal setting. People who have just had a stroke need time
      to understand many of the terms and concepts that treating clinicians use, and
      new models need to acknowledge the importance of health literacy if both patients
      and carers are to participate in the rehabilitation process. People that have had
      a stroke have an important role to play in the development of these new models.

PMID- 21184018
TI  - Community education clarifies career choice in an allied health professions
      course.
AB  - Community education, a form of experiential learning, balances academic content
      with experiences, teaching students to apply learning to life experiences.
      Community education is introduced in the course, "Professional Roles and
      Environments in Health Care," which allows students to explore allied health
      careers to help them identify a health profession of interest. Students indicated
      that community education is a valuable academic exercise, allowing them to
      acquire real world experiences, interact with health professionals, and relate
      classroom learning.

PMID- 21184019
TI  - HIPAA and FERPA: competing or collaborating?
AB  - The Family Educational Rights and Privacy Act (FERPA) was established in 1974 to
      protect the privacy of student educational records. The Health Insurance
      Portability and Accountability Act (HIPAA) had its first part implemented in 2002
      with the goal of protecting the privacy of patient health information. But what
      happens when the student is a patient? Does one follow FERPA or HIPAA or both?
      This article examines that question and guides schools through the HIPAA/FERPA
      intersection. Schools need to consider their individual situations, as there is
      not a "one size fits all." In addition, one word in the HIPAA or FERPA law can
      make a difference. What also has to be taken into account is individual state law
      where the school or patient is located. It is hoped that in the future the
      language of the laws will be ameliorated such that the focus can be on the
      students and patients and not deciphering what law to follow.

PMID- 21184021
TI  - Random thoughts about the world of periodicals.

PMID- 21184020
TI  - Blended learning: emerging best practices in allied health workforce development.
AB  - To remain dynamic and viable, academic institutions preparing the future
      workforce need to convert to a more accessible and convenient pathway for
      students. The need for responsiveness is especially true when considering
      strategies to prepare an allied health workforce in areas of shortages and to
      meet the needs of the underserved. A blended or hybrid learning model that
      strategically uses web-based and face-to-face teaching/learning methods is an
      innovative and strategic way that promotes learner-centered higher education and
      facilitates a higher learning experience. A model and emerging best practices for
      implementation are presented from our experience at the Center for Allied Health
      Programs at the University of Minnesota.

PMID- 21184022
TI  - Recommendations for physical and occupational therapy practice from the
      perspective of clients undergoing therapy for breast cancer-related impairments.
AB  - Evidence points to the efficacy of physical and occupational therapy intervention
      for the management of impairments and functional limitations related to the
      treatment of breast cancer. However, few studies give voice to the women
      participating in the physical rehabilitation programs intended to ameliorate
      their deficits. OBJECTIVE: The purpose of this qualitative investigation was to
      explore the experience of physical rehabilitation as well as to identify
      recommendations for physical and occupational therapy practice from the
      perspective of the client undergoing therapy for breast cancer-related
      impairments. DESIGN: A phenomenological design was chosen and included a
      purposive sample of women (n = 10) undergoing physical rehabilitation for
      impairments related to breast cancer treatment. Data included semistructured
      interviews and artifact examination. METHODS: Ten semistructured interviews were
      conducted at a setting of the participants' choice. Data collection continued
      until saturation was reached. Data analysis was cyclical and ongoing and involved
      all six researchers in analyzing and triangulating all pieces of data. Member
      checks and a peer review were conducted to confirm relevance and validity.
      RESULTS: Five themes emerged: 1) challenges with obtaining referrals, 2)
      challenges with patient education, 3) improvements in functional impairments, 4)
      emotional support, and 5) benefits of a specialized clinic environment.
      CONCLUSIONS: Consideration of the five themes led to four recommendations for
      physical and occupational therapist practice from the perspective of the client:
      1) advocate for presurgical therapy consultations, 2) be competent in the
      management of all impairments and functional limitations associated with breast
      cancer treatment, 3) be aware of the emotional support the therapist has the
      capacity to provide or not provide, and 4) as much as possible, create an
      inviting, nonclinical environment.

PMID- 21184023
TI  - Leadership in athletic training: implications for practice and education in
      allied health care.
AB  - Leadership behaviors are an important aspect of athletic training and are needed
      within all allied health care disciples. A two-phase, exploratory, non
      experimental research study using a Delphi technique and a randomly selected
      sample of athletic trainers (n = 161) was conducted to determine leadership
      competencies perceived to be important for athletic training practice and
      education. The Delphi technique (phase one) resulted in the Leadership
      Development in Athletic Training instrument (LDAT). In the national survey (phase
      two), respondents used the LDAT to rate the importance of leadership competencies
      for athletic training practice and for athletic training education. Coefficient
      alphas ranged from alpha = 0.83 to 0.97 and provided satisfactory estimates of
      internal consistency. Concurrent, construct, and convergent validity were
      established. Forty-nine leadership competencies were rated important for practice
      and 48 for education (M = 1.5, p <= 0.001). Exploratory factor analysis revealed
      that leadership competencies were organized by four constructs (with six
      emphases): 1) personality characteristics, 2) diagnosing context and people
      skills, 3) communication and initiative, and 4) strategic thinking. Repeated
      measures ANOVA with Sidak post-hoc adjustments indicated each leadership
      construct significantly increased in importance as the level of the ATEP
      progressed.

PMID- 21184024
TI  - Effects of an experiential learning program on the clinical reasoning and
      critical thinking skills of occupational therapy students.
AB  - This study examined the effects of participation in a 1-week, experiential, hands
      on learning program on the critical thinking and clinical reasoning skills of
      occupational therapy students. A quasi-experimental, nonrandomized pre- and post
      test design was used with a sample of 25 students. The students had completed
      three semesters of didactic lecture coursework in a master's level OT educational
      program prior to participation in a hands-on therapy program for children with
      hemiplegic cerebral palsy. Changes in critical thinking and clinical reasoning
      skills were evaluated using the following dependent measures: Self-Assessment of
      Clinical Reflection and Reasoning (SACRR) and the California Critical Thinking
      Skills Test (CCTST). Changes in pretest and posttest scores on the SACRR and the
      CCTST were statistically significant (p>0.05) following completion of the
      experiential learning program. This study supports the use of hands-on learning
      to develop clinical reasoning and critical thinking skills in healthcare
      students, who face ever more diverse patient populations upon entry-level
      practice. Further qualitative and quantitative investigations are needed to
      support the results of this study and determine which components of experiential
      learning programs are essential for developing clinical reasoning and critical
      thinking skills in future allied health professionals.

PMID- 21184025
TI  - Dietetic preceptor educational needs from the preceptor, student, and faculty
      perspectives.
AB  - Quality dietetic education relies on strong preceptors to encourage, motivate,
      and teach dietetic students so that they can excel as practitioners. The purpose
      of this study was to examine the needs of dietetic preceptors, determine how
      those needs should be met, and suggest who can best address those needs. Grounded
      theory methodology was used to design this study of preceptor needs. Focus groups
      and one-on-one interviews were conducted with 22 preceptors, 5 former students,
      and 4 faculty members of a clinical dietetic training program. Data were analyzed
      using open, axial, and selective coding. The central category/ factor that
      influenced preceptor participation and effectiveness was determined to be lack of
      time. Preceptors felt they did not have sufficient time to devote to precepting
      students. Other categories found to be important for successful precepting
      included student-preceptor orientation, the teaching-learning environment, views
      of dietetic professionalism, and the responsibilities and rewards of precepting.
      Based on the themes that emerged with this grounded theory methodology, this
      study suggests that preceptors should be trained in the following five areas: 1)
      basic teaching skills, 2) time management strategies, 3) methods for coaching
      students, 4) adult learning styles, and 5) methods for providing constructive
      feedback. This training should increase the likelihood that the experience will
      be both time-efficient and successful for the preceptor, student, and faculty
      involved. This should improve the effectiveness of preceptors as educators, which
      should consequently facilitate recruitment and retention of dietetic preceptors.

PMID- 21184026
TI  - Attitudes of different professionals toward the well-being of older adults living
      at home.
AB  - OBJECTIVES: Negative attitudes in society toward working in eldercare constitute
      a challenge to educators and care providers. The purpose of this study was to
      explore, describe, and compare the attitudes of different professional groups
      toward factors that are important for the well-being of older adults. METHODS: A
      randomized sample of 210 respondents that included registered nurses (RNs),
      registered occupational therapists (OTRs), personal benefit advisors (PBAs), and
      home help assistants (HHAs) was collected from social service agencies in 10
      Swedish municipalities. A scale was developed in a six-step process to measure
      attitudes toward factors influencing elder well-being, and the final 22-item
      Likert-type scale was called the "Staff Attitudes toward the Well-being of Older
      Adults" scale. RESULTS: Thirty-three percent of staff responded with positive
      attitudes toward working with elders, and the remaining were uncertain or
      negative. The attitudes of RNs, OTRs, and PBAs were significantly more positive
      than those of HHAs. DISCUSSION: The scale is practical for use in different
      professional groups with the aim of exploring existing attitudes, identifying
      areas with a low degree of prevailing positive attitudes and differences between
      groups, and evaluating whether attitudes change after staff training.

PMID- 21184027
TI  - Forming partnerships: Indiana-Ohio Center for Traumatic Amputation Rehabilitation
      Research.
AB  - As schools of allied health and health professions must increasingly conform to
      the research missions of their universities, positioning for faculty and funding
      resources will require creative collaborations among institutions. In 2004
      Indiana University Purdue University Indianapolis and the Ohio State University
      collaborated to create the Indiana-Ohio Center for Traumatic Amputation
      Rehabilitation Research which received substantial funding through the Department
      of Defense to support a project of significant national importance. This article
      describes the initial vision of the project, the development of the
      organizational structure, and the research agenda that produced a unique model
      that is now generating substantial research data for dissemination. Also
      described are factors contributing to the success of the Center, including the
      emphasis on strategic partnerships and plans for sustainability and expansion of
      the Center as a national research enterprise.

PMID- 21184028
TI  - A transdisciplinary definition of diagnosis.
AB  - Diagnosis is a fundamental abstract reasoning concept in healthcare. It forms the
      foundation for clinical guidelines, evidence-based practice, and healthcare
      interventions. The definition of diagnosis is evolving in a manner that may
      change patient care and clinical research. Currently, dictionary definitions of
      diagnosis fall into two broad categories, those that stress the original
      etymology and those that are based on classifying the patient problem according
      to preexisting labels. Many medical diagnoses are not sufficient to justify
      allied health, profession-specific interventions. Some authors have suggested
      profession-specific definitions of diagnosis and profession-specific
      nomenclature. However, a unique set of labels that are insulated from other
      health professions has been difficult to achieve because of the interdependence
      of pathology, impairments, and the patient's role in society. Coordinated
      interdisciplinary or transdisciplinary patient care, including clinical
      guidelines, and efficient delivery of services necessitate a definition that
      facilitates communication across health care professions. A solution to this
      dilemma may be to create a bridge, recognizing the multifactorial etiology of
      health and professional autonomy while explicitly stating the context of
      profession-specific interventions as a team approach. I propose that the
      definition of diagnosis be modified to: "the process of determining mechanisms by
      which the patient's health condition arises and the conclusions reached by doing
      so."

PMID- 21184029
TI  - Allied health-today and tomorrow. 1973.

PMID- 21184030
TI  - Differential forms of p53 in medulloblastoma primary tumors, cell lines and
      xenografts.
AB  - Medulloblastoma is the most common malignant brain tumor in childhood. The most
      prevalent chromosomal abnormalities are isochromosome 17q and loss of 17p, the
      location of the tumor suppressor gene p53. Mutations in the p53 gene in
      medulloblastoma are relatively infrequent but have recently been correlated to
      poor prognosis. Furthermore, the p53 gene encodes nine different isoforms, which
      may have a profound impact on p53 tumor suppressor activity. Nine medulloblastoma
      primary biopsy samples, six cell lines from medulloblastoma, and one from a
      supratentorial PNET, and a medulloblastoma xenograft, along with human brain and
      visceral tissues, were analyzed by Western blotting, using monoclonal p53
      antibodies against two regions in the N-terminus or the central domain.
      Medulloblastoma primary tissue and xenografts present low molecular weight
      proteins recognized by both N-terminal p53 antibodies that are absent in all cell
      lines including the one used for xenografts. Normal visceral organs display short
      forms of p53, and low levels of canonical p53. Normal brain structures, including
      cerebellum, contained only canonical size p53 at high levels. In conclusion, our
      results indicate that the presence of p53 isoforms may play a functional role in
      medulloblastoma. The observed differences in their presence in cell lines and
      derived xenografts, suggest that p53 should be investigated in in vivo models
      rather than in cell lines.

PMID- 21184032
TI  - [Patient education on risks of epidural anesthesia. Demands on medical diligence
      in obstetrics].

PMID- 21184031
TI  - beta-hydroxy-beta-methylbutyrate (HMB) attenuates muscle and body weight loss in
      experimental cancer cachexia.
AB  - beta-hydroxy-beta-methylbutyrate (HMB), a leucine metabolite, improves muscle
      mass and function. This study aimed at evaluating the effects of HMB
      administration in an experimental in vivo model of cancer cachexia (CC). Wistar
      rats were randomized to receive standard or 4% HMB-enriched chow. Rats from both
      groups were randomized to receive an i.p. inoculum of AH-130 cells (TB). All rats
      were weighed and sacrificed at day 24. Liver, heart and muscles were dissected
      and weighed. The protein levels of p-p70S6k, p-eIf2alpha, p-mTOR and p-4-EB-P1
      were evaluated by Western blotting on gastrocnemius muscle (GSN). As expected,
      the growth of the AH-130 ascites hepatoma induced significant carcass weight and
      GSN muscle loss. HMB treatment significantly increased GSN and heart weight in
      controls (p=0.002 and p<0.001, respectively). In HMB-treated TB, body weight was
      not lost but significantly (p=0.003) increased, and GSN loss was significantly
      (p=0.04) attenuated with respect to TB. Phosphorylated eIF2alpha markedly
      decreased in TB-rats vs. C. Feeding the HMB-enriched diet resulted in decreased p
      eIF2alpha levels in control animals, while no changes could be observed in the TB
      group. Phosphorylated p70S6K and phosphorylated mTOR were markedly increased by
      HMB treatment in controls and further increased in TB. Phosphorylated 4-EB-P1 was
      markedly increased in TB but substantially unaffected by HMB treatment.
      Administration of HMB attenuates body weight and muscle loss in experimental CC.
      Increased phosphorylation of key anabolic molecules suggests that these actions
      are mediated by improved protein anabolism in muscle.

PMID- 21184033
TI  - [Postpartum eclampsia and fulminant HELLP syndrome].
AB  - Postpartum onset of eclampsia and HELLP (hemolysis, elevated liver enzymes, low
      platelet count) syndrome is a rare but life-threatening complication for both
      mother and fetus. A case of a 38-year-old parturient (gravida 2, para 1) who was
      asymptomatic prior to delivery is reported. Emergency caesarean section had to be
      performed due to sudden onset of fetal bradycardia as a result of partial
      placental separation. The perioperative course was characterized by new onset
      hypertension, nausea and restlessness; within 2 h the patient suffered a
      generalized seizure which was treated with magnesium sulfate and hydralazine.
      Despite management in accordance with current guidelines, the condition
      deteriorated with hypotension, anemia and renal failure. On further examination
      hematomas in the abdominal cavity and walls were identified and laboratory tests
      confirmed HELLP syndrome with severe coagulopathy. Explorative laparotomy
      revealed diffuse bleeding without a significant isolated source or postpartum
      uterine hemorrhage. Retrospectively, the anemia could be ascribed to severe
      hemolysis and diffuse bleeding from coagulopathy. The patient required packed red
      cells, platelets, fresh frozen plasma and prothrombin complex. After admission to
      the intensive care unit persistent diffuse bleeding mainly caused by
      hyperfibrinolysis and renal failure occurred, which required blood transfusion,
      antifibrinolytic (tranexamic acid) and renal replacement therapy (continuous veno
      venous hemodiafiltration with citrate) for 6 days. The patient recovered without
      any sequelae and was discharged 26 days later. Placental separation with new
      onset peripartum hypertension is to be interpreted as a precursor of severe
      gestosis and associated complications, especially disseminated intravascular
      coagulation (DIC), acute renal failure and pleural effusion. A differentiation
      between a rapid drop in hemoglobin concentration secondary to hemolysis in
      postpartum HELLP syndrome rather than postpartum hemorrhage can be challenging.
      In addition, HELLP syndrome can lead to rapidly developing, fulminant
      hyperfibrinolysis in the context of DIC. Keys to successful management of
      postpartum gestosis and associated complications are early detection and
      perception of clinical and laboratory warning signs, a multidisciplinary approach
      with rapid and consistent targeted symptomatic therapy to save the mother and
      fetus.

PMID- 21184034
TI  - [Pain management of burn injuries].
AB  - Burn injuries represent a severe form of acute pain. In spite of improvements in
      wound treatment and pain regimens during recent years, the management of burn
      pain still remains a common problem and a tremendous challenge for clinical
      staff. An efficient pain treatment plan contributes to a fast and uneventful
      course and is an important part of the therapeutic management by plastic
      surgeons, anesthesiologists, psychologists and physiotherapists. Extensive
      pharmacokinetic alterations, additional neuropathic components and multiple
      dressing changes or therapeutic procedures need a flexible and dynamic pain
      strategy. A standardized continuous pain assessment and documentation are a
      cornerstone of burn pain control. In addition to pharmacological methods non
      pharmacological procedures can play an important role and should be started early
      during burn patient therapy.

PMID- 21184035
TI  - [Palliative care and end-of-life patients in emergency situations.
      Recommendations on optimization of out-patient care].
AB  - BACKGROUND: At the end of life acute exacerbations of medical symptoms (e.g.
      dyspnea) in palliative care patients often result in emergency medical services
      being alerted. The goals of this study were to discuss cooperation between
      emergency medical and palliative care structures to optimize the quality of care
      in emergencies involving palliative care patients. METHODS: For data collection
      an open discussion of the main topics by experts in palliative and emergency
      medical care was employed. Main outcome measures and recommendations included
      responses regarding current practices related to expert opinions and
      international literature sources. RESULTS: As the essential points of consensus
      the following recommendations for optimization of care were named: (1)
      integration of palliative care in the emergency medicine curricula for pre
      hospital emergency physicians and paramedics, (2) development of outpatient
      palliative care, (3) integration of palliative care teams into emergency medical
      structures, (4) cooperation between palliative and emergency medical care, (5)
      integration of crisis intervention into outpatient palliative emergency medical
      care, (6) provision of emergency plans and emergency medical boxes, (7) provision
      of palliative crisis cards and do not attempt resuscitation (DNAR) orders, (8)
      psychosocial aspects concerning palliative emergencies and (9) definition of
      palliative patients and their special situation by the physician responsible for
      prior treatment. CONCLUSIONS: Prehospital emergency physicians are confronted
      with emergencies in palliative care patients every day. In the treatment of these
      emergencies there are potentially serious conflicts due to the different
      therapeutic concepts of palliative medical care and emergency medical services.
      This study demonstrates that there is a need for regulated criteria for the
      therapy of palliative patients and patients at the end of life in emergency
      situations. Overall, more clinical investigations concerning end-of-life care and
      unresponsive palliative care patients in emergency medical situations are
      necessary.

PMID- 21184036
TI  - [Personnel planning in the emergency department. Optimized patient care round the
      clock].
AB  - In recent years the number of interdisciplinary emergency departments (ED) at
      hospitals in Germany has increased. The model of decentralized first contact
      units for each medical discipline has been abandoned, last but not least due to
      economic considerations. While decentralized units could be staffed with
      personnel from each discipline there is much controversy surrounding the question
      of which kind of doctor is best suited for a centralized ED. The development of
      programs providing the necessary qualification for German ED physicians in the
      future by working groups of several specialties is still nascent and has not yet
      produced concrete results. However, even without these special training programs,
      the management of critically ill or severely injured patients in the ED is
      paramount. The smooth operation of centralized EDs is therefore important.
      Therefore, taking into account economical aspects, qualification and number of
      available personnel, this article introduces a staffing concept as a rational
      basis for an optimized patient management in centralized EDs in Germany. Taking
      the patient characteristics, the specific treatment modalities and the number of
      admissions to the ED into account, this paper will determine treatment time per
      patient and the necessary number of physicians, as well as an optimized staffing
      model for EDs.

PMID- 21184038
TI  - [Abnormal x-ray finding after central venous catheterization].
AB  - Central venous catheter placement can cause a variety of complications, such as
      catheter fracture, loss of the guide wire and embolization. In the case reported
      a large bore central venous catheter was used in a 32-year-old patient undergoing
      surgery for vertebral body fracture of the thoracic spine. After a complication
      free surgical procedure the post-operative x-ray showed an abnormal finding. A
      piece of the guide wire was suspected to have been left in the patient. However,
      this possibility could be ruled out by the anesthesiologist who inserted the
      catheter. With an additional x-ray and CT scan of an identical catheter it could
      then be demonstrated that the abnormal finding was caused by polyurethane pins
      which are integrated in the catheter.

PMID- 21184037
TI  - [Intravenous administration of lidocaine for perioperative analgesia. Review and
      recommendations for practical usage].
AB  - Lidocaine is commonly used for regional anesthesia and nerve blocks. However,
      recent clinical studies demonstrated that intravenous perioperative
      administration of lidocaine can lead to better postoperative analgesia, reduced
      opioid consumption and improved intestinal motility. It can therefore be used as
      an alternative when epidural analgesia is contraindicated, not possible or not
      feasible. Apart from the sodium channel blocking effects relevant for regional
      anesthesia, lidocaine also has anti-inflammatory properties. Lidocaine can
      obviously inhibit the priming of resting neutrophilic granulocytes, which,
      simplified, may reduce the liberation of superoxide anions, a common pathway of
      inflammation after multiple forms of tissue trauma. At the authors' institutions
      intravenous lidocaine is primarily used for postoperative pain relief following
      abdominal surgery and is given as a bolus dose of 1.5-2.0 mg/kg body weight (BW)
      injected over 5 min followed by an infusion of 1.5 mg/kg BW/h intraoperatively
      and 1.33 mg/kg BW/h postoperatively in the recovery room or in the intensive care
      unit (ICU). The lidocaine infusion is stopped in the recovery room 30 min before
      discharge or in the ICU at the latest after 24 h. Lidocaine is not used on normal
      wards. This overview summarizes the current evidence for the intravenous
      administration of lidocaine for patients undergoing different types of surgery
      and gives practical advice for its use.

PMID- 21184039
TI  - [Operational availability of ground-based emergency medical services in Rheinland
      Palatinate: state-wide web-based system for collation, display and analysis].
AB  - BACKGROUND: A growing number of reports have been published in Germany related to
      problems with the operational readiness of mobile emergency physician services,
      although no systematic analyses have yet been presented. However, such
      investigations form the prerequisite for the deployment of countermeasures.
      METHODS: Rhineland-Palatinate (4,060,000 inhabitants, 7,753 mi(2)) is a typical
      territorial state in the southwest of Germany with extensive wooded areas
      covering 42% of the state and only few metropolitan areas. These basic conditions
      represent a challenge to the provision of state-wide emergency medical services
      (EMS). On behalf of the Ministry of the Interior a web-based platform for the
      collation, display and analysis of the operational readiness of all 68 ground
      based physician-staffed emergency units within the state was developed. Of these
      units 61 are affiliated to hospitals and 7 units to medical practices and 89,000
      emergency missions are carried out annually. RESULTS: Within the study period
      (April 2009-March 2010) 56 of the 68 units (82.4%) reported 1 or more periods of
      unavailability of operational readiness. In total 2,613 periods of temporary
      unavailability were documented with a mean duration of 8.9 h. The mean
      unavailability of operational readiness was 3.9% for the whole state, 6.2% for
      the northern and 1.6% for the southern EMS districts. In 7 of the units (10.3%)
      the degree of unavailability exceeded 5% and in 8 units (11.7%) it exceeded 10%.
      Two thirds of all suspended services were the result of shortages of emergency
      physicians, with considerably higher deficits at bases affiliated with hospitals
      of lower levels of care or in rural regions. CONCLUSIONS: This tool enables the
      large-scale collation and analysis of the operational readiness of physician
      based ambulance services. Currently the state does not suffer from a general lack
      of emergency physicians. However, rural areas as well as bases affiliated with
      small hospitals show a considerable deficit in operational readiness caused by a
      shortage of staff. These deficits may be partially compensated by optimized
      planning and disposition within rescue coordination centers. Moreover, they call
      for corrective actions in the light of health care politics. In addition,
      analyses of other elements of EMS (i.e. rescue helicopters) should be undertaken.

PMID- 21184041
TI  - [Validation of an advance directive].
AB  - BACKGROUND: German Legislation has defined the legal significance of advance
      directives (AD). Nevertheless, many precast ADs are of limited help in clinical
      decision making. Empirical results are rare and controversial. The SUPPORT study
      showed that precast ADs had a tendency to being ignored. Value-based AD proved to
      be of help in the interpretation of patients' wills by physicians. We therefore
      investigated whether a value-based AD that can be individualized with the help of
      a check-box-system is a valid instrument of communicating the patient's
      preferences. This is the first validation of an AD. MATERIAL AND METHODS: In our
      study we evaluated the acceptance and practicability of an AD. Questionnaires and
      the AD itself were handed out to patients, relatives, and members of the nursing
      and medical staff. All were asked to fill out the AD, mark all unclear passages,
      make amendments to the AD if wanted and finally were asked to answer a
      questionnaire regarding the AD. The level of significance was defined at 5%,
      meaning that every "unwanted" answer exceeding 5% or passages with more than 5%
      of the total remarks were analyzed and it was checked whether changes to the AD
      should be made. RESULTS: The return rate was 64.8% (201 of 310). The results were
      highly positive for the items "understandable" (81,6%), "clarifying" (65,7%),
      "helpful" (76,1%), and "sensible" (75,1%). 70% of patients and relatives stated
      that they were able to express personal wishes and values with this AD, as well
      as a majority of the medical staff (44% vs. 30%). The discrepancy between the
      groups was significant (ChiSq=13.11, p<.001). All paragraphs of the check-box
      system were validated as understandable and clear in intention. Major concerns
      were the inability of expressing own wishes and values (by 16,4% of all
      participants) and the fear of later alterations (15,4%). According to the
      findings and the evaluations the AD was modified. DISCUSSION: The value-based AD
      which is routinely used in a university hospital and which can be individualized
      by a check-box-system was broadly accepted by the test subjects and showed highly
      positive results with respect to the analyzed items. Only minor changes were
      derived from our study to hopefully raise its acceptance even more. The
      discrepancy between patients, relatives and the medical staff concerning the
      possibility to express one's wishes and values was surprising and in
      contradiction to former findings. However, our study cannot answer whether the
      higher level of distrust among medical staff can be explained by negative
      professional experiences. CONCLUSION: The investigated AD with a check box system
      seems to be an adequate instrument to communicate patient's wishes and
      directives.

PMID- 21184040
TI  - [Thrombotic microangiopathy after extracorporeal circulation: important
      differential diagnosis].
AB  - Thrombotic microangiopathies are characterized by platelet activation,
      endothelial damage, hemolysis and microvascular occlusion. This group of diseases
      is primary represented by thrombotic thrombocytopenic purpura (TTP) and hemolytic
      uremic syndrome (HUS). Patients present with microangiopathic hemolytic anemia
      and thrombocytopenia as well as occlusion-related organ ischemia to a variable
      degree. A deficiency of the metalloprotease ADAMTS-13 is a major risk for acute
      disease manifestation as this is a regulator of unusually large von Willebrand
      factor (vWF) multimers, which are extremely adhesive and secreted by endothelial
      cells. In classical TTP an ADAMTS-13 activity below 5% is specific, whereas in
      other forms of thrombotic microangiopathies activity of ADAMTS-13 ranges from
      very low to normal. Symptoms of different forms of thrombotic microangiopathy are
      frequently overlapping and a clear classification according to clinical criteria
      is often difficult. Due to a high mortality, particularly of TTP, immediate
      diagnosis and therapy are essential. In this article two cases of thombotic
      microangiopathy after cardiac surgery are reported. After exclusion of TTP and
      HUS as well as other etiologies of thrombotic microangiopathy a relationship
      between the use of extracorporeal circulation and the pathogenesis of thrombotic
      microangiopathy is assumed.

PMID- 21184043
TI  - [Intraosseous infusion in the pediatric emergency medical service. Analysis of
      emergency medical missions 1990-2009].
AB  - BACKGROUND: Timely establishment of venous access in infants and toddlers during
      emergency medical care can be a particularly challenging task. Alternative routes
      for drug and fluid administration, such as endobronchial, intramuscular, central
      venous or venous cut-down do not offer reliable solutions. Intraosseous infusion
      (IOI) has become established as an effective alternative intravascular access for
      rapid and efficient drug delivery. IOI was introduced in our local emergency
      medical service (EMS) in 1993 and was assigned a high priority in international
      guidelines for pediatric emergency medical care in 2000 and 2005. The aim of this
      study was to review the impact of the introduction of IOI on drug administration
      routes during prehospital emergency treatment of critically ill or severely
      injured pediatric patients (NACA index V-VII) in our tertiary medical care centre
      over a period of 20 years. METHODS: Pediatric prehospital emergency medical
      protocols from 1990 to 2009 were analyzed with respect to the administration
      routes for fluids and medications in severely injured or critically ill children
      with NACA severity scores V-VII. The frequency and mode of vascular access during
      prehospital treatment including IOI, endobronchial administration, central venous
      catheterization (CVC) and intramuscular administration as well as prehospital
      treatment and transportation without vascular access were analyzed. Two groups
      were compared: the introduction phase of IOI between 1990 and 1999 and the phase
      of growing IOI routine after introducing guidelines and regular staff IOI
      technique training between 2000 and 2009. Demographic data and drug
      administration routes in the two different time periods were analyzed using the
      Mann-Whitney-u test and t-test or chi(2)-test, respectively. A p-value <0.05 was
      regarded as significant. RESULTS: A total of 5,279 pediatric prehospital
      emergency charts were analyzed and 401 patients (7.6%) were scored as NACA V-VII.
      At the emergency scene 299 patients (75%) received a peripheral intravenous
      access, 3 (0.7%) a central venous line access, 77 (19%) an intraosseous needle
      and in 22 (5.4%) no vascular or intraosseous access was used during the course of
      prehospital treatment (NACA VII - 13 patients, NACA VI - 2 patients, NACA V - 7
      patients). Of the NACA VII patients 3 were transported under continuous
      cardiopulmonary resuscitation without vascular access. After 2002 all patients
      with NACA index VII were treated with vascular or intraosseous access. In 48
      patients (12%) at least initial medication was given by the endobronchial or
      alternative route but within the last 3 years endobronchial drug administration
      was no longer reported. Thus, in 124 critically ill patients (31%) routine
      peripheral venous access could not be established initially or until the end of
      treatment (77 times IOI, 22 times no access over the course of treatment, 3 times
      CVC and 22 times initial endobronchial followed by peripheral venous access).
      Over the reviewed period the use of IOI increased significantly (p<0.001), while
      the incidence of lacking vascular access (p<0.05) and alternative drug
      administration routes (p<0.001) continuously decreased. CONCLUSION: The IOI
      technique has not only been assigned a high priority in the guidelines for
      pediatric emergency care of critically ill children with difficult or failed
      venous access but has also significantly influenced current prehospital care. The
      introduction of the IOI technique in our prehospital pediatric emergency system
      has markedly reduced the number of critically ill or severely injured pediatric
      patients without vascular access or with less reliable alternative administration
      routes in the last 20 years.

PMID- 21184042
TI  - [Type A dissection. Principles of anesthesiological management].
AB  - Acute type A dissection is among the most dangerous of vascular diseases and is
      associated with a high lethality. Surgery for type A dissection is a complex
      procedure which is accompanied by relevant blood losses and severe deterioration
      of the coagulation system. Either due to the dissection or the surgical
      procedure, perfusion of affected organs can be diminished or completely disrupted
      with the risk of irreversible organ damage especially in the brain. Perioperative
      anesthesiological management for type A dissection is demanding and involves
      maintaining hemodynamic stability, surveillance of cerebral oxygenation and
      transesophageal echocardiographical diagnostic support for the decision-making of
      the most appropriate surgical approach. Furthermore, reestablishment of
      sufficient hemostasis can be challenging and requires thorough understanding of
      the relevant aspects affecting normal hemostasis during surgical repair of aortic
      dissection. In this article relevant pathophysiological aspects and basic
      principles of anesthesiological management of type A dissection are described.

PMID- 21184044
TI  - [Interventional lung assist membrane ventilator. Successful use despite heparin
      induced thrombocytopenia type II].
AB  - Pumpless extracorporeal carbon dioxide elimination using the interventional lung
      assist (iLA) membrane ventilator is a modern concept for the treatment of
      hypercapnia due to respiratory failure which cannot be sufficiently treated by
      conventional strategies. Heparin-induced thrombocytopenia type II (HIT II) is
      considered to be an absolute contraindication for placement of an iLA because of
      the system's heparin-coated diffusion membrane. The example demonstrates that iLA
      therapy can be continued despite occurrence of a HIT II in terms of an "off label
      use". In the case described, postoperative therapy using the iLA membrane
      ventilator was installed in a 69-year-old patient with severe ARDS after elective
      lung resection. Despite a confirmed HIT II detected in the course of iLA, this
      therapy was continued after changing systemic anticoagulation to argatroban. The
      platelet count increased again and the patient could be successfully weaned from
      the iLA membrane and finally transferred to a rehabilitation centre.

PMID- 21184045
TI  - [Persistent extramedullary plasmacytoma of the nose after radiotherapy].
AB  - Solitary extramedullary plasmacytomas of the head and neck are rare tumors. These
      tumors are known to be very radiosensitive and therefore radiotherapy is often
      considered as the treatment of choice. We present the case of a solitary
      extramedullary plasmacytoma of the nose which did not respond sufficiently to
      radiotherapy, i.e. persistence of the tumor led to surgical treatment. After a
      discussion of the recent literature we primarily recommend the excision of this
      type of tumor whenever possible.

PMID- 21184046
TI  - [Current aspects in ultrasonography of the salivary glands].
AB  - Ultrasonography is a basic diagnostic tool in all diseases of the salivary
      glands. Due to their relatively superficial anatomic location, distinct borders
      and homogenous echotexture, the salivary glands are ideally positioned for
      sonographic assessment. The advantages of this technique include its high
      diagnostic accuracy, non-invasiveness, lack of radiation exposure, as well as
      high reproducibility and low costs. Progress in ultrasound equipment and
      ultrasound transducers in recent years, i.e. colour-coded Doppler sonography with
      and without contrast enhancers, tissue harmonic imaging and elastography have
      widened the spectrum of indications and diagnostic accuracy. Although unspecific,
      many diseases of the salivary glands have particular sonographic characteristics.
      In addition, ultrasound-guided fine-needle biopsy is able to obtain material for
      cytological analysis in a targeted fashion under visual control. Compared to
      other imaging techniques such as CT and MRI, ultrasound achieves the highest
      sensitivity in the identification of neoplasms in the salivary glands.

PMID- 21184048
TI  - The identification and mapping of candidate genes and QTL involved in the fatty
      acid desaturation pathway in Brassica napus.
AB  - We constructed a linkage map for the population QDH, which was derived from a
      cross between an oilseed rape cultivar and a resynthesised Brassica napus. The
      linkage map included ten markers linked to loci orthologous to those encoding
      fatty acid biosynthesis genes in Arabidopsis thaliana. The QDH population
      contains a high level of allelic variation, particularly in the C genome. We
      conducted quantitative trait locus (QTL) analyses, using field data obtained over
      3 years, for the fatty acid composition of seed oil. The population segregates
      for the two major loci controlling erucic acid content, on linkage groups A8 and
      C3, which quantitatively affect the content of other fatty acids and is a problem
      generally encountered when crossing "wild" germplasm with cultivated "double low"
      oilseed rape cultivars. We assessed three methods for QTL analysis, interval
      mapping, multiple QTL mapping and single marker regression analysis of the subset
      of lines with low erucic acid. We found the third of these methods to be most
      appropriate for our main purpose, which was the study of the genetic control of
      the desaturation of 18-carbon fatty acids. This method enabled us to decouple the
      effect of the segregation of the erucic acid-controlling loci and identify 34 QTL
      for fatty acid content of seed oil, 14 in the A genome and 20 in the C genome.
      The QTL indicate the presence of 13 loci with novel alleles inherited from the
      progenitors of the resynthesised B. napus that might be useful for modulating the
      content or extent of desaturation of polyunsaturated fatty acids, only one of
      which coincides with the anticipated position of a candidate gene, an orthologue
      of FAD2.

PMID- 21184049
TI  - Trichome density of main stem is tightly linked to PepMoV resistance in chili
      pepper (Capsicum annuum L.).
AB  - A relationship between pepper trichome and pepper mottle virus (PepMoV)
      resistance was examined. In an intraspecific F(2) mapping population from the
      cross between Capsicum annuum CM334 (trichome-bearing and PepMoV resistant) and
      Chilsungcho (glabrous and PepMoV susceptible), major QTLs for both traits were
      identified by composite interval mapping in linkage group (LG) 24 corresponding a
      telomere region on pepper chromosome 10. Ptel1 of putative trichome enhancing
      locus was a common major QTL for trichome density on the main stem and calyx.
      Ptel1 apart from HpmsE031 at a 1.03 cM interval was specifically associated to
      the trichome density on the main stem, whereas Ptel2 near m104 marker on LG2 was
      specific for the calyx trichome. Epistatic analysis indicated that Ptel1 engaged
      in controlling the trichome density by mutual interactions with the organ
      specific QTLs. For PepMoV resistance, two QTLs (Pep1 and Pep2) were identified on
      the LG 24. Pep1 was located with Ptel1 in the R-gene cluster (RGC) for potyvirus
      resistance including Pvr4 with broad spectrum resistance to potyviruses. Pep1
      flanking TG420 marker seemed to be the major factors determining correlation with
      PepMoV resistance. These results indicate that the level of trichome density on
      pepper main stem can be used as a morphological marker for Pvr4 in pepper
      breeding.

PMID- 21184050
TI  - An analysis of sequence variability in eight genes putatively involved in drought
      response in sunflower (Helianthus annuus L.).
AB  - With the aim to study variability in genes involved in ecological adaptations, we
      have analysed sequence polymorphisms of eight unique genes putatively involved in
      drought response by isolation and analysis of allelic sequences in eight inbred
      lines of sunflower of different origin and phenotypic characters and showing
      different drought response in terms of leaf relative water content (RWC). First,
      gene sequences were amplified by PCR on genomic DNA from a highly inbred line and
      their products were directly sequenced. In the absence of single nucleotide
      polymorphisms, the gene was considered as unique. Then, the same PCR reaction was
      performed on genomic DNAs of eight inbred lines to isolate allelic variants to be
      compared. The eight selected genes encode a dehydrin, a heat shock protein, a non
      specific lipid transfer protein, a z-carotene desaturase, a drought-responsive
      element-binding protein, a NAC-domain transcription regulator, an auxin-binding
      protein, and an ABA responsive-C5 protein. Nucleotide diversity per synonymous
      and non-synonymous sites was calculated for each gene sequence. The pi (a)/pi (s)
      ratio range was usually very low, indicating strong purifying selection, though
      with locus-to-locus differences. As far as non-coding regions, the intron showed
      a larger variability than the other regions only in the case of the dehydrin
      gene. In the other genes tested, in which one or more introns occur, variability
      in the introns was similar or even lower than in the other regions. On the
      contrary, 3'-UTRs were usually more variable than the coding regions. Linkage
      disequilibrium in the selected genes decayed on average within 1,000 bp, with
      large variation among genes. A pairwise comparison between genetic distances
      calculated on the eight genes and the difference in RWC showed a significant
      correlation in the first phases of drought stress. The results are discussed in
      relation to the function of analysed genes, i.e. involved in gene regulation and
      signal transduction, or encoding enzymes and defence proteins.

PMID- 21184051
TI  - Residue dynamics of clopyralid and picloram in rape plant rapeseed and field
      soil.
AB  - A new method for simultaneous analysis of clopyralid and picloram residues in
      rape plant, rapeseed and field soil was developed and validated. The residual
      dynamics and final residues of clopyralid and picloram in rape plant, rapeseed
      and soil were determined by high performance liquid chromtography-diode array
      detector (HPLC-DAD) and high performance liquid chromtography-mass spectroscopy
      detector (HPLC-MSD). The limit of quantification (LOQ) was established as 0.02
      mg/kg for soil sample, 0.5 mg/kg for rape and rapeseed sample, respectively. It
      was shown that recoveries ranged from 71.3%-109.0% for clopyralid, and 84.0%
      100.5% for picloram at fortified levels of 0.02-2 mg/kg. From residue trials at
      two geographical experimental plots in China and laboratory simulated pots, the
      results showed that the half-lives of clopyralid in rape and soil were 3.66-4.83
      and 2.53-5.17 days, respectively, for picloram with half-lives of 5.17-10.73 and
      3.45-7.11 days. For tirals applied according to the label recommended, at harvest
      time the final residues of clopyralid in rapeseed were below 1.82 mg/kg, while
      the picloram residues could not be detected in rapeseed (<LOQ).

PMID- 21184052
TI  - Effect of agrochemical use on the drinking water quality of Agogo, a tomato
      growing community in Ashanti Akim, Ghana.
AB  - The effect of agrochemical use in agricultural activities on the drinking water
      quality of ground and surface water within Agogo, a prominent tomato growing area
      in the Ashanti region of Ghana was assessed by monitoring physicochemical
      parameters, trace metals and microbial quality of two water sources. Levels of
      contamination were greater in surface water than groundwater. Trace metal levels
      (mg/L) were 1.40, 0.12, 0.08 and 0.18 in surface water and 0.08, 0.10, 0.05 and
      0.08 in groundwater for Fe, Pb, Zn and Cd, respectively. Lead and Cd in surface
      and groundwater exceeded USEPA maximum acceptable levels (MCLs) for drinking
      water. Bacterial indicator numbers (geometric means/100 mL) in surface water
      varied from 9.35 x 105 to 1.57 x 1011 for total coliforms, 4.15 x 104 to 2.10 x
      107 for faecal coliforms and 2.80 x 10 to 3.25 x 102 for enterococci, but none
      was found in groundwater.

PMID- 21184053
TI  - Observation of sward destruction caused by irrigation with toxic Microcystis
      morphospecies containing water in Southern Hungary.
AB  - In the summer of 2006 bloom-like phenomenon occurred in a garden pond in Szeged,
      Southern Hungary. After regular watering of a sward with pond water containing
      the algal mass, destruction of garden grass occurred. Microcystis aeruginosa,
      Microcystis viridis, Microcystis ichthyoblabe, and Microcystis wesenbergii were
      identified by light microscopy in the water sample; microcystin-FR, -LR, -RR and 
      YR were determined by matrix-assisted laser desorption/ionization--time-of-flight
      analysis. There was an 80% decrease in the green mass (87% in chlorophyll
      content) of the grass in a 1 m2 area of the garden irrigated with pond water.

PMID- 21184055
TI  - Metabolomics: biomarkers of disease and drug toxicity.

PMID- 21184056
TI  - Potential of poly(styrene-co-divinylbenzene) monolithic columns for the LC-MS
      analysis of protein digests.
AB  - Two polystyrene-based capillary monolithic columns of different length (50 and
      250 mm) were used to evaluate the effects of column length on gradient separation
      of protein digests. A tryptic digest of a 9-protein mixture was used as a test
      sample. Peak capacities were determined from selected extracted ion
      chromatograms, and tandem mass spectrometry data were used for database matching
      using the MASCOT search engine. Peak capacities and protein identification scores
      were higher for the long column with all gradients. Peak capacities appear to
      approach a plateau for longer gradient times; maximum peak capacity was estimated
      to be 294 for the short column and 370 for the long column. Analyses with similar
      gradient slope produced a ratio of the peak capacities of 3.36 for the long and
      the short column, which is slightly higher than the expected value of the square
      root of the column length ratio. The use of a longer monolith improves peptide
      separation, as reflected by higher peak capacity, and also increases protein
      identification, as observed from higher identification scores and a larger number
      of identified peptides. Attention has also been paid to the peak production rate
      (PPR, peak capacity per unit time). For short analysis times, the short column
      produces a higher PPR, while for analysis times longer than 40 min, the PPR of
      the 250-mm column is higher.

PMID- 21184054
TI  - Markers of bone turnover for the prediction of fracture risk and monitoring of
      osteoporosis treatment: a need for international reference standards.
AB  - The International Osteoporosis Foundation (IOF) and the International Federation
      of Clinical Chemistry and Laboratory Medicine (IFCC) recommend that a marker of
      bone formation (serum procollagen type I N propeptide, s-PINP) and a marker of
      bone resorption (serum C-terminal telopeptide of type I collagen, s-CTX) are used
      as reference analytes for bone turnover markers in clinical studies.
      INTRODUCTION: Bone turnover markers (BTM) predict fracture risk, and treatment
      induced changes in specific markers account for a substantial proportion of
      fracture risk reduction. The aims of this report were to determine their clinical
      potential in the prediction of fracture risk and for monitoring the treatment of
      osteoporosis and to set an appropriate research agenda. METHODS: Evidence from
      prospective studies was gathered through literature review of the PUBMED database
      between the years 2000 and 2010 and the systematic review of the Agency for
      Healthcare Research and Quality up to 2001. RESULTS: High levels of BTMs may
      predict fracture risk independently from bone mineral density in postmenopausal
      women. They have been used for this purpose in clinical practice for many years,
      but there is still a need for stronger evidence on which to base practice. BTMs
      provide pharmacodynamic information on the response to osteoporosis treatment,
      and as a result, they are widely used for monitoring treatment in the individual.
      However, their clinical value for monitoring is limited by inadequate
      appreciation of the sources of variability, by limited data for comparison of
      treatments using the same BTM and by inadequate quality control. IOF/IFCC
      recommend one bone formation marker (s-PINP) and one bone resorption marker (s
      CTX) to be used as reference markers and measured by standardised assays in
      observational and intervention studies in order to compare the performance of
      alternatives and to enlarge the international experience of the application of
      markers to clinical medicine. CONCLUSION: BTM hold promise in fracture risk
      prediction and for monitoring treatment. Uncertainties over their clinical use
      can be in part resolved by adopting international reference standards.

PMID- 21184058
TI  - High hydrostatic pressure and biology: a brief history.
AB  - Pressure as a thermodynamical parameter was successively introduced in physics,
      hydrometallurgy, geochemistry, and biology. In all cases, the main objective was
      to recreate a natural phenomenon (gas or liquid compressibility, synthesis or
      crystal growth of minerals, survival of deep sea microorganisms...). The
      introduction of high hydrostatic pressure (HHP) in Biology was an important
      scientific feature over the last hundred years. This paper describes the
      different steps that have led to the spreading of pressure in biology and the
      opening of new frontiers either in basic and applied researches due to the
      specific characteristics of the pressure parameter. Because of the low energy
      conveyed by this parameter, leading to the preservation of most organoleptic
      properties of foods, and its ability to inactivate many pathogens, the use of HHP
      began to spread at the end of the twentieth century into the food industry, in
      particular for the development of pathogen inactivation processes. Today, even if
      this field is still the first application domain for HHP, more and more research
      works have shown that this parameter could be of great interest in health and
      medicine sciences.

PMID- 21184057
TI  - Ultrasonographic evaluation of the free intraperitoneal fluid in asymptomatic
      children.
AB  - BACKGROUND: Free intraperitoneal fluid can be an important sign in an abdominal
      inflammatory process or abdominal trauma. It is often present in children with
      abdominal pain, but it is a nonspecific finding. A minimal amount of free
      intraperitoneal fluid is considered normal. OBJECTIVE: The purpose of this study
      was to evaluate the incidence, location and volume of free fluid in the abdomen
      and pelvis in a population of asymptomatic children. MATERIALS AND METHODS: In
      this prospective study, we performed clinically indicated abdominal and pelvic
      sonography, using high-resolution transducers, in 200 asymptomatic children: 104
      (52%) girls, 96 (48%) boys; ages 6 days-15 years (mean 3 years 8 months). US
      studies were performed and prospectively evaluated by two experienced pediatric
      radiologists. Patients with any condition that could result in the accumulation
      of free intraperitoneal fluid as well as postpubertal girls were excluded from
      the study. RESULTS: Free intraperitoneal fluid was seen in 12 children (6%), only
      in the pelvis. Fluid volume never exceeded 1 ml. CONCLUSION: Our study suggests
      that 1 ml or less of free intraperitoneal fluid detected in the pelvis is
      probably insignificant.

PMID- 21184059
TI  - Bioconversion of substituted naphthalenes and beta-eudesmol with the cytochrome
      P450 BM3 variant F87V.
AB  - Bioconversion of various substituted naphthalenes that contain 1-methoxy- and 1
      ethoxy-naphthalenes, methylnaphthalenes, dimethylnaphthalenes, and
      naphthalenecarboxylic acid methyl esters were performed using recombinant
      Escherichia coli cells, which expressed the gene coding for a cytochrome P450 BM3
      variant F87V (P450 BM3 (F87V)) that was N-terminally fused to an archaeal
      peptidyl-prolyl cis-trans isomerase. In addition, bioconversion experiments with
      the same substrates were carried out using those that expressed the phnA1A2A3A4
      genes for a polycyclic aromatic hydrocarbon (PAH)-dihydroxylating dioxygenase,
      which originated from a PAH-utilizing marine bacterium Cycloclasticus sp. strain
      A5. Consequently, a variety of mono-hydroxylated derivatives were generated from
      these substituted naphthalenes. Oxidative aryl coupling was found to produce a
      novel compound 4,4'-diethoxy-[2,2']-binaphthalenyl-1,1'-diol from 1
      ethoxynaphthalene with the E. coli cells expressing the P450 BM3 (F87V) gene.
      This recombinant E. coli was further shown to introduce the hydroxyl group regio-
      and stereo-specifically into a sesquiterpene beta-eudesmol.

PMID- 21184060
TI  - Biomass production and nutrient uptake by Neochloris oleoabundans in an open
      trough system.
AB  - The purpose of this paper is to present biomass and nutrient uptake data from
      Neochloris oleoabundans production in an open trough system. The growth medium
      used was BG11, temperature ranged from 16.7  degrees C to 25.3  degrees C, and pH
      ranged from 5.52 to 9.94 because the customary pH increase during algal biomass
      production was moderated by incoming CO(2) gas streams (atmospheric, 2%, 4%, and
      6% CO(2)). Peak concentrations of algal biomass ranged from 643 to 970 mg L(-1),
      specific growth rates ranged from 0.15 to 0.37 day(-1), and doubling times ranged
      from 4.8 to 1.9 days. Carbon, nitrogen, and phosphorus were incorporated into the
      biomass at 0.05%, 8.3%, and 54% of supplied amounts. Open growth systems
      supplemented with CO(2) should be designed to regulate medium pH within the range
      of 6.3 to 7.1. Future research should examine various media and alternative
      carbon sources to decrease doubling times, increase peak concentrations, and
      optimize nutrient uptake.

PMID- 21184061
TI  - Seasonal variability of bacteria in fine and coarse urban air particulate matter.
AB  - The current knowledge about the microbial communities associated with airborne
      particulate matter, particularly in urban areas, is limited. This study aims to
      fill this gap by describing the microbial community associated with coarse (PM10)
      and fine (PM2.5) particulate matter using pyrosequencing. Particulate matter was
      sampled on Teflon filters over 3 months in summer and 3 months in winter in Milan
      (Italy), and the hypervariable V3 region of the gene 16S rRNA amplified from the
      DNA extracted from the filters. The results showed large seasonal variations in
      the microbial communities, with plant-associated bacteria dominating in summer
      and spore-forming bacteria in winter. Bacterial communities from PM10 and PM2.5
      were also found to differ from each other by season. In all samples, a high
      species richness, comparable with that of soils, but a low evenness was found.
      The results suggest that not only can the sources of the particulate influence
      the presence of specific bacterial groups but also that environmental factors and
      stresses can shape the bacterial community.

PMID- 21184062
TI  - Biodegradation of fenvalerate and 3-phenoxybenzoic acid by a novel
      Stenotrophomonas sp. strain ZS-S-01 and its use in bioremediation of contaminated
      soils.
AB  - A bacterial strain ZS-S-01, newly isolated from activated sludge, could
      effectively degrade fenvalerate and its hydrolysis product 3-phenoxybenzoic acid
      (3-PBA). Based on the morphology, physiological biochemical characteristics, and
      16 S rDNA sequence, strain ZS-S-01 was identified as Stenotrophomonas sp. Strain
      ZS-S-01 could also degrade and utilize deltamethrin, beta-cypermethrin, beta
      cyfluthrin, and cyhalothrin as substrates for growth. Strain ZS-S-01 was capable
      of degrading fenvalerate rapidly without a lag phase over a wide range of pH and
      temperature, even in the presence of other carbon sources, and metabolized it to
      yield 3-PBA, then completely degraded it. No persistent accumulative product was
      detected by HPLC and GC/MS analysis. Studies on biodegradation in various soils
      showed that strain ZS-S-01 demonstrated efficient degradation of fenvalerate and
      3-PBA (both 50 mg.kg(-1)) with a rate constant of 0.1418-0.3073 d(-1), and half
      lives ranged from 2.3 to 4.9 days. Compared with the controls, the half-lives for
      fenvalerate and 3-PBA reduced by 16.9-156.3 days. These results highlight strain
      ZS-S-01 may have potential for use in bioremediation of pyrethroid-contaminated
      environment.

PMID- 21184063
TI  - Extramural venous invasion by gastrointestinal malignancies: CT appearances.
AB  - The purpose of this article is to describe and demonstrate the appearances of
      extramural vascular invasion on computed tomography in gastrointestinal
      malignancies as one of the pathways of disease spread. In this article, we
      demonstrate the imaging features with pathologically proven examples, along with
      a brief description of relevant vascular anatomy. We shall also discuss the
      clinical significance and prognostic implications of extramural vascular invasion
      in gastrointestinal malignancies.

PMID- 21184065
TI  - Customized planning of augmentation mammaplasty with silicon implants using three
      dimensional optical body scans and biomechanical modeling of soft tissue outcome.
AB  - The aesthetic results of augmentation mammaplasty are essentially determined by
      the size and the shape of the implant as well as its position on the chest. To
      achieve successful aesthetic results, customized surgery planning based on a
      reliable visual concept of the prospective surgery outcome and quantitative
      methods for assessment of three-dimensional (3D) breast shape could be of
      considerable additional value. This report evaluates a novel method for
      customized planning and quantitative optimization of breast augmentation based on
      3D optical body scanning of the patient's breast and computational modeling of
      soft tissue mechanics. This method allows a 3D photo-realistic appearance of
      postsurgery breasts to be simulated for different surgical scenarios. It also
      allows the result of a virtual simulation to be implemented using measurements
      derived from a computationally predicted breast model. A series of clinical
      studies are presented that demonstrate the feasibility and accuracy of the
      proposed approach for customized 3D planning of breast augmentation, including
      direct comparison between simulated and postsurgery results. Our experimental
      results show that for 89% of the breast surface, the average difference between
      the simulated and postsurgery breast models amounts to less than 1 mm. The
      presented method for customized planning of augmentation mammaplasty enables
      realistic prediction and quantitative optimization of postsurgery breast
      appearance. Based on individual 3D data and physical modeling, the described
      approach enables more accurate and reliable predictions of surgery outcomes than
      conventionally used photos of prior patients, drawings, or ad hoc data
      manipulation. Moreover, it provides precise quantitative data for bridging the
      gap between virtual simulation and real surgery.

PMID- 21184064
TI  - Performing an additional decubitus series at CT colonography.
AB  - PURPOSE: To determine the rate and associated factors for acquiring a decubitus
      series at CT colonography (CTC), in addition to the standard supine and prone
      series. MATERIALS AND METHODS: CTC examinations read centrally at one institution
      but performed at three different centers in 6,380 adults were reviewed to
      determine the frequency of an additional decubitus series. Results were analyzed
      according to study indication (primary screening vs. diagnostic for incomplete
      colonoscopy), practice site (academic vs. community), patient age, gender, body
      mass index (BMI), and temporal variation. At all sites, the CT technologist
      determined the need for an additional decubitus series, with infrequent
      radiologist input in select cases. RESULTS: The frequency for the CT technologist
      to obtain a decubitus series at screening was 9.7% (578/5,952), compared with
      22.9% (98/428) following failed colonoscopy (P < 0.001). The decubitus rate for
      screening at the academic center (9.4%, 550/5,871) was significantly lower than
      the community hospitals (34.6% combined, 28/81) (P < 0.001). The rate
      progressively increased with age, from 5.0% under age 50 to 28.0% over age 80. No
      significant difference was seen between men and women (10.3 vs. 9.2%), but a
      strong correlation existed with increased BMI, rising to >25% for BMI over 40.
      Marked temporal variation existed at the academic center, with quarterly rates
      ranging from 0 to 17%. CONCLUSIONS: The frequency for performing a third series
      at CTC varies considerably according to indication, practice site, patient age,
      BMI, and time. These results have important implications for clinical practice,
      including the need for improved training and feedback for CT technologists.

PMID- 21184066
TI  - Influence of platelet-rich plasma on the histologic characteristics of the
      autologous fat graft to the upper lip of rabbits.
AB  - BACKGROUND: This study evaluated the influence of platelet-rich plasma (PRP) on
      the histologic characteristics of autologous fat grafts to the upper lip of
      rabbits. METHODS: Nine New Zealand white rabbits were used. Eight of the rabbits
      underwent fat harvest from the groin fat pads using a modified Coleman technique.
      One side of the upper lip was infiltrated with autologous fat and the other side
      with fat and PRP. Four of the infiltrated rabbits were killed 8 weeks after the
      lip augmentation, and the remaining four infiltrated rabbits plus one control
      case were killed 12 weeks after the procedure. Coronal sections of both upper
      lips were analyzed microscopically to evaluate the quality of the fat graft, the
      inflammatory reaction, the presence of oil cysts, the degree of fibrosis, and the
      neovascularization. RESULTS: The infiltration of adipose tissue plus PRP
      presented less inflammatory reaction (p < 0.05) and fewer oil cysts (p < 0.05)
      than the infiltration of adipose tissue without PRP. CONCLUSIONS: The
      infiltration of fat tissue plus PRP generates a lower inflammatory reaction and
      less formation of oil cysts than the infiltration of isolated fat. Platelet-rich
      plasma increases the maintenance of the transplanted fat cells.

PMID- 21184067
TI  - Aesthetic improvements of skin grafts in nasal tip reconstruction.
AB  - Defect closure on the nasal tip subunit still remains challenging. Full-thickness
      skin transplantation still is used despite its poor outcome in terms of the nasal
      tip contour caused by lack of dermal tissue. To avoid subsidence deformities
      associated with nasal tip reconstruction with skin transplants, this study
      analyzed methods using combined epidermal and dermal replacement. For 30
      consecutive patients with a nasal tip defect, a retrospective comparison was made
      between conventional full-thickness skin transplantation, retroauricular
      perichondrodermal composite grafts, and skin transplantation supplemented with
      the collagen-elastin matrix, Matriderm, used as a dermal substitute (n = 10 per
      study group).The postoperative results were evaluated in a randomized and blind
      manner by external facial surgeons using the Manchester Scar Scale. The findings
      showed a marked improvement in nasal tip contour with combined epidermal/dermal
      replacement without any deterioration in other graft qualities, justifying the
      additional effort involved in this procedure. Two patients developed fistulae
      after Matriderm-aided skin transplantation. Therefore, the authors do not
      consider this a suitable method for nasal tip reconstruction.

PMID- 21184069
TI  - The use of tissue glue in prominent ear correction surgery.
AB  - Cyanoacrylate tissue glues have been used for many years in otoplasty and
      specific indications for its use are as described. As well as being an effective
      means of dressing the postauricular suture line, its use in gluing the pinna back
      to the postauricular skin may negate the use of the head bandage in the
      postoperative period.

PMID- 21184070
TI  - The true incidence of near-term postoperative complications in prosthetic breast
      reconstruction utilizing human acellular dermal matrices: a meta-analysis.
AB  - BACKGROUND: The use of human acellular dermal matrix (HADM) materials in
      prosthetic-based breast reconstruction has gained popularity in recent years.
      Questions remain, however, regarding the nature and incidence of postoperative
      complications associated with this technique. The results reported in the
      available literature vary widely. This meta-analysis examines this question
      further with a broad review of the available literature in an effort to better
      define the true nature and incidence of near-term complications associated with
      the use of HADM in prosthetic-based breast reconstruction. It does not aim to
      compare this method of reconstruction to others. METHODS: A review of the
      available literature was performed in July 2009. The goal was to identify all
      previous works describing the placement of HADM at prosthetic-based breast
      reconstruction. Included were studies that documented the use of HADM for
      coverage of tissue expanders or permanent implants following therapeutic or
      prophylactic mastectomy. Excluded were studies that reported on the use of HADM
      in cosmetic breast surgery or studies that included the use of xenografts. Data
      collected included demographics as well as the nature and incidence of
      complications, with separate categories assigned for seroma, infection, flap
      necrosis, and "other." Data were analyzed using Comprehensive Meta-Analysis((r))
      software (Biostat, Englewood, NJ). Raw proportions, fixed-effect models, and
      random-effect models were used to assess the complication rates across studies.
      RESULTS: Eleven published articles and one abstract that was later published as
      an article were identified. Within these 12 studies, a total of 789 breasts were
      identified that had undergone reconstruction with HADM. The mean follow-up was
      13.7 months. Under the random-effects model, the total complication rate was
      12.0%. The most common complications were flap necrosis (3.3%), seroma (3.3%),
      and infection (5.6%). All complications not included in these categories were set
      apart in a separate category, "Other," and totaled 3.0% CONCLUSION: The true
      incidence of postoperative complications in the near term utilizing HADM in
      prosthetic-based breast reconstruction appears to be approximately 12%. The
      incidence of long-term complications such as capsular contracture remains
      unknown. However, as surgical experience with HADM grows, operative techniques
      designed at reducing risks will mature, strategies for managing complications
      will advance, and more advanced products designed to reduce the incidence of
      complications are likely to become available.

PMID- 21184071
TI  - Hyperbaric oxygen therapy: solution for difficult to heal acute wounds?
      Systematic review.
AB  - BACKGROUND: Hyperbaric oxygen therapy (HBOT) is used to treat various wound
      types. However, the possible beneficial and harmful effects of HBOT for acute
      wounds are unclear. METHODS: We undertook a systematic review to evaluate the
      effectiveness of HBOT compared to other interventions on wound healing and
      adverse effects in patients with acute wounds. To detect all available randomized
      controlled trials (RCTs) we searched five relevant databases up to March 2010.
      Trial selection, quality assessment, data extraction, and data synthesis were
      conducted by two of the authors independently. RESULTS: We included five trials,
      totaling 360 patients. These trials, with some methodologic flaws, included
      different kinds of wound and focused on different outcome parameters, which
      prohibited meta-analysis. A French trial (n = 36 patients) reported that
      significantly more crush wounds healed with HBOT than with sham HBOT [relative
      risk (RR) 1.70, 95% confidence interval (CI) 1.11-2.61]. Moreover, there were
      significantly fewer additional surgical procedures required with HBOT (RR 1.60,
      95% CI 1.03-2.50), and there was significantly less tissue necrosis (RR 1.70, 95%
      CI 1.11-2.61). In one of two American trials (n = 141) burn wounds healed
      significantly quicker with HBOT (P < 0.005) than with routine burn care. A
      British trial (n = 48) compared HBOT with usual care. HBOT resulted in a
      significantly higher percentage of healthy graft area in split skin grafts (RR
      3.50, 95% CI 1.35-9.11). In a Chinese trial (n = 145) HBOT did not significantly
      improve flap survival in patients with limb skin defects. CONCLUSIONS: HBOT, if
      readily available, appears effective for the management of acute, difficult to
      heal wounds.

PMID- 21184072
TI  - Prediction of anastomotic leak and its prognosis in digestive surgery.
AB  - BACKGROUND: Anastomotic leak (AL) is a dangerous postoperative complication in
      gastrointestinal surgery. The present study focuses on whether our prediction
      scoring system, "Estimation of Physiologic Ability and Surgical Stress" (E-PASS),
      could predict occurrence of AL and its prognosis in various kinds of
      gastrointestinal surgical procedures. METHODS: We prospectively investigated
      parameters of E-PASS, absence or presence of AL, and in-hospital mortality in
      6,005 patients who underwent elective digestive surgery with alimentary tract
      reconstruction in 45 acute care hospitals in Japan between 1 April 2002 and 31
      March 2007. RESULTS: Incidences of AL were 19.6% for esophagectomy via right
      thoracotomy and laparotomy, 11.7% for pancreaticoduodenectomy, 7.4% for low
      anterior resection, 4.0% for total gastrectomy, 1.8% for open distal gastrectomy,
      1.3% for open colectomy, for an overall incidence of 4.1%. The incidence in each
      procedure significantly correlated with median value of surgical stress score of
      the E-PASS (R = 0.78, n = 11, p = 0.0048). The incidences of AL increased when
      Total Risk Points (TRP) of the E-PASS increased; 1.1% at the TRP range of <500,
      2.8% at 500 to <1,000, 4.8% at 1,000 to <1,500, and 13.6% at >= 1,500 (p <
      0.0001). In patients who suffered from AL, an in-hospital mortality rate at TRP <
      1,000 was significantly lower than that at TRP of >= 1,000 (1.1 vs. 15.9%; p =
      0.00019). CONCLUSIONS: The E-PASS, requiring only nine variables, may be useful
      in predicting AL and its prognosis.

PMID- 21184073
TI  - Endarterectomy of the aneurysm sac in open abdominal aortic aneurysm repair
      reduces perigraft seroma and improves graft incorporation.
AB  - BACKGROUND: Fluid around the graft in the original aneurysm sac after open
      abdominal aortic aneurysm (AAA) repair is a poorly researched phenomenon. If
      large, such perigraft seroma can cause symptoms of compression, and cases of
      rupture have even been described. We assessed whether endarterectomy of the
      aneurysm sac reduces the incidence of perigraft fluid and improves graft
      incorporation. DESIGN AND METHODS: Starting in July 2005, all patients with
      elective open AAA repair were alternately treated either with conventional
      thrombectomy or thrombectomy plus endarterectomy of the aneurysm sac. All
      patients were treated with a polytetrafluoroethylene (PTFE) graft. The maximum
      axial width of the perigraft fluid collection was measured on computed tomography
      (CT) scans 1 year after operation. RESULTS: The CT scans of 115 patients were
      available; 56 had endarterectomy of the aneurysm sac and 59 did not. Fluid
      collections were significantly smaller in patients with endarterectomy (median
      width 4.0 versus 8.0 mm; P = 0.0001). Eight patients with endarterectomy had a
      fluid collection wider than 10 mm compared to 28 patients without endarterectomy
      (OR 0.18, 95% CI 0.07-0.46). After endarterectomy, 17 patients had radiological
      signs of complete graft incorporation in comparison to only 6 patients without
      endarterectomy (OR 3.85, 95% CI 1.39-10.66). No patients were symptomatic or
      reoperated for perigraft seroma. CONCLUSIONS: Endarterectomy of the aneurysm sac
      in open AAA repair appears to improve graft incorporation. The high rate of
      asymptomatic perigraft seroma is surprising, and its clinical significance is
      unknown. Ultrafiltration of PTFE grafts may be an underlying mechanism.

PMID- 21184074
TI  - Laparoscopic repeat resection of recurrent hepatocellular carcinoma.
AB  - BACKGROUND: The present study was designed to explore the safety and feasibility
      of laparoscopic re-resection of recurrent liver tumors. METHODS: Among 120
      hepatocellular carcinoma patients who received laparoscopic hepatectomy, six were
      carefully selected to receive laparoscopic re-resection. Surgical indications
      were evaluated by specific selection criteria for tumor location, size,
      metastases, vessel invasion, and liver function. Four patients received
      laparoscopic partial hepatectomy, and two received laparoscopic anatomical left
      lateral lobe resection. Results were analyzed retrospectively. RESULTS: The six
      surgeries (four laparoscopic partial hepatectomies, two laparoscopic anatomical
      left lateral lobe resections) were successfully performed with no intraoperative
      complications. Mean operative time was 140.83 +/- 35.69 min, mean blood loss was
      283.33 +/- 256.25 ml, and mean hospital stay was 5.67 +/- 1.63 days. CONCLUSIONS:
      Our experience with carefully selected cases meeting specific criteria suggests
      that laparoscopic hepatic re-resection is a safe, feasible procedure that may
      offer multiple benefits for treating recurrent hepatocellular carcinoma.

PMID- 21184075
TI  - Histological and immediate postoperative outcome after preoperative cetuximab:
      case-matched control study.

PMID- 21184076
TI  - Final pathology findings after immediate or delayed surgery in patients with
      cytologically benign or follicular thyroid nodules.
AB  - BACKGROUND: In the present study, we reviewed our experience with thyroid
      cytological findings showing benign or follicular tumor and evaluated the
      outcomes in patients who had undergone immediate or late surgical treatment.
      METHOD: In 2007, 445 patients underwent initial surgical therapy for benign or
      follicular thyroid nodules according to our criteria for surgical indication. Of
      these, 320 patients underwent thyroid excision immediately. In the remaining 125
      patients, surgery was performed after follow-up for more than 18 months. RESULTS:
      In this series, the frequencies of finding thyroid carcinoma pathologically were
      11.6 and 6.4% in patients undergoing immediate and late surgery, respectively. In
      these 445 patients, there was no significant difference in age, tumor size, serum
      thyroglobulin, or nodule growth rate between benign and malignant thyroid
      nodules. There was, however, a significant difference in ultrasonographic
      classification. CONCLUSIONS: Our criteria for surgical indication of nodules
      diagnosed as cytological benign or follicular tumors were considered appropriate.
      Ultrasonographic evaluation is an important and useful basis for therapeutic
      decision making in choosing either immediate surgery or observation for
      cytologically diagnosed benign or follicular tumors.

PMID- 21184077
TI  - Endoscopic minimally invasive thyroidectomy: a prospective proof-of-concept study
      in humans.

PMID- 21184078
TI  - Predictive risk factors for intra- and postoperative complications in 526
      laparoscopic sigmoid resections due to recurrent diverticulitis: a multivariate
      analysis.
AB  - BACKGROUND: Laparoscopic sigmoid resection is a feasible and frequent operation
      for patients who suffer from recurrent diverticulitis. There is still an ongoing
      debate about the optimal timing for surgery in patients who suffer from recurrent
      diverticulitis episodes. In elective situations the complication rate for this
      procedure is moderate, but there are patients at high risk for perioperative
      complications. The few identified risk factors so far refer to open surgery. Data
      for the elective laparoscopic approach is rare. The objective of this study was
      to identify potential predictive risk factors for intra- and postoperative
      complications in patients who underwent laparoscopic sigmoid resection due to
      diverticular disease. METHODS: Uni- and multivariate analyses of a prospectively
      gathered database (1993-2006) were performed on a consecutive series of 526
      patients who underwent laparoscopic sigmoid resection due to recurrent
      diverticulitis in a single institution. Patients were assessed for demographic
      data, operative indications, and intra- and postoperative complications.
      Altogether, we analyzed 17 potential risk factors to identify significant
      influence on the intra- and postoperative outcome, including timing of surgery.
      RESULTS: Statistical analysis of specific medical and surgical complications
      revealed anemia, previous myocardial infarction, heart failure, experience of the
      surgeon, and male gender, as independent predictive risk factors for
      postoperative complications. Patients older than age 75 years was the only
      independent risk factor for intraoperative complications in a multiple logistic
      regression model. Early elective surgery led to increased conversion rate but did
      not influence the postoperative complication rate. CONCLUSIONS: This large,
      single-center study provides first evidence of the significance of specific
      predictive risk factors for intra- and postoperative complications in
      laparoscopic sigmoid resection for diverticular disease.

PMID- 21184079
TI  - Ileocecal junction: anatomic, histologic, radiologic and endoscopic studies with
      special reference to its antireflux mechanism.
AB  - AIM: The aim of the study was to perform histomorphologic, endoscopic, and
      radiologic studies of the ileocecal junction (ICJ). A clearer understanding of
      the anatomical structure of the ICJ may shed some light on its function. METHODS:
      Histomorphologic studies were performed in 18 cadavers and radiologic in 22 and
      endoscopic in 10 healthy volunteers. Morphologic studies were done with the help
      of a magnifying loupe: histologic sections were stained with hematoxylin and
      eosin and Masson's trichrome. The ICJ was studied radiologically using the method
      of small bowel meal. Endoscopic study was done under controlled air inflation
      using a video endoscope. RESULTS: A nipple (1.5-2 cm long) with transversely
      lying stoma protruded from the medial wall of the cecum. A fornix was found on
      each side. The nipple stoma was surrounded by two lips: upper and lower. A
      mucosal fold started at both angles of the stoma and extended along the cecal
      circumference. It was marked on the outer cecal aspect by a groove. CONCLUSION:
      The ileocecal nipple is a muscular tube with a transversely lying stoma and is
      suspended to the cecal wall by a "suspensory ligament". The morphologic structure
      of the ileocecal nipple was confirmed endoscopically and radiologically. The
      ileocecal nipple was closed at rest and opened upon terminal ileal contraction to
      deliver ileal contents to the cecum. It evacuated the barium periodically into
      the cecum. The ileocecal nipple structure seems to be adapted to serve the
      function of cecoileal antireflux.

PMID- 21184080
TI  - Combined therapy associating systemic platinum-based chemotherapy and local
      radiotherapy into the treatment of primary intraocular lymphoma.

PMID- 21184081
TI  - A decision-making Fokker-Planck model in computational neuroscience.
AB  - In computational neuroscience, decision-making may be explained analyzing models
      based on the evolution of the average firing rates of two interacting neuron
      populations, e.g., in bistable visual perception problems. These models typically
      lead to a multi-stable scenario for the concerned dynamical systems.
      Nevertheless, noise is an important feature of the model taking into account both
      the finite-size effects and the decision's robustness. These stochastic dynamical
      systems can be analyzed by studying carefully their associated Fokker-Planck
      partial differential equation. In particular, in the Fokker-Planck setting, we
      analytically discuss the asymptotic behavior for large times towards a unique
      probability distribution, and we propose a numerical scheme capturing this
      convergence. These simulations are used to validate deterministic moment methods
      recently applied to the stochastic differential system. Further, proving the
      existence, positivity and uniqueness of the probability density solution for the
      stationary equation, as well as for the time evolving problem, we show that this
      stabilization does happen. Finally, we discuss the convergence of the solution
      for large times to the stationary state. Our approach leads to a more detailed
      analytical and numerical study of decision-making models applied in computational
      neuroscience.

PMID- 21184083
TI  - How host defense is encoded in the mammalian genome.
AB  - This issue of Mammalian Genome explores the genetic approach to infectious
      disease susceptibility as it has been applied in mammals. Although no single
      issue of any journal could give comprehensive treatment to a field so extensive
      and rapidly growing as this one, these texts describe key discoveries that
      provided new understanding of immune responses. Classical genetic studies opened
      and continue to pave the way to deep understanding of many issues in immunology.

PMID- 21184082
TI  - Dynamic contrast-enhanced magnetic resonance imaging and pharmacokinetic models
      in prostate cancer.
AB  - Dynamic contrast-enhanced MRI enables noninvasive analysis of prostate
      vascularization as well as tumour angiogenesis and capillary permeability
      characteristics in prostate cancers. Pharmacokinetic models summarizing the
      complex information provided by signal intensity-time curves for a few
      quantitative pharmacokinetic parameters are increasingly being used in the
      routine clinical setting. This review consists of two parts. The first part
      discusses the advantages and disadvantages of the MR pulse sequences that can be
      used for performing DCE-MRI and also of the most widely used pharmacokinetic
      parameters and models and the parameters they describe. The second part outlines
      the range of current and potential future clinical applications of DCE-MRI and
      pharmacokinetic parametric maps in patients with prostate cancer, with reference
      to the current scientific literature on the topic. The potential clinical
      applications of DCE-MRI for prostate cancer include detection, localization, and
      staging, differentiation of recurrent cancer and estimation of the patient's
      prognosis, as well as monitoring of treatment response.

PMID- 21184085
TI  - Comment to the paper "Posterior fossa decompression and the cerebellum in Chiari
      type II malformation: a preliminary MRI study".

PMID- 21184084
TI  - Glucose and fructose uptake by Limulus polyphemus hepatopancreatic brush border
      and basolateral membrane vesicles: evidence for Na+-dependent sugar transport
      activity.
AB  - [(3)H]-fructose and [(3)H]-glucose transport activities were determined in brush
      border membrane vesicles (BBMV) and basolateral membrane vesicles (BLMV) from
      Limulus polyphemus (horseshoe crab) hepatopancreas. Glucose transport was
      equilibrative in the absence of sodium and sodium dependent in the presence of
      sodium in BBMV, suggesting GLUT-like and SGLT-like transport activity. Glucose
      transport by BLMV was equilibrative and sodium independent. Fructose uptake by
      BBMV and BLMV was equilibrative in the absence of sodium and sodium dependent in
      the presence of sodium. Western blot analysis using a rabbit anti-mouse SGLT-1
      polyclonal antibody indicated the presence of a cross-reacting horseshoe crab
      BBMV protein of similar molecular weight to the mammalian SGLT1. Sequence
      alignment of the mouse SGLT-4 and SGLT1 with a translated, horseshoe crab
      expressed sequence tag also indicated significant identity between species.
      Fructose and glucose uptake in the absence and presence of sodium by
      hepatopancreas BBMV and BLMV indicated the presence of sodium-dependent transport
      activity for each sugar that may result from the presence of transporters similar
      to those described for other species.

PMID- 21184086
TI  - Renal impairment caused by temporary loop ileostomy.
AB  - PURPOSE: Creation of a temporary loop ileostomy is a standard surgical procedure.
      This study was undertaken to determine whether dehydration associated with the
      ileostomy causes renal impairment. METHODS: The prospective data from 107
      consecutive patients undergoing temporary loop ileostomy between 2004 and 2009
      was evaluated. GFR was calculated at the time of hospital discharge after
      constructing the ileostomy and at the time of deciding to close the ileostomy.
      RESULTS: The average GFR at the time of discharge after constructing the
      ileostomy was a median of 92.50 (60.75-223.88); at the time of deciding to close
      the ileostomy, it was 75.25 (4-135.13) ml/min/1.73 m(2) (p < 0.001). In 20
      patients renal function decreased, with a GFR <60 ml/min/1.73 m(2) during the
      ileostomy period; in six of these 20 patients, the decrease was severe (GFR <30
      ml/min/1.73 m(2)). Underlying diseases, reasons for constructing ileostomies,
      sex, and time interval to closure did not affect renal function. Patients in whom
      GFR was decreased at the time of deciding to close the ileostomy presented with
      significantly more closure-related surgical complications. CONCLUSIONS: Renal
      impairment is a well-known potential complication of loop ileostomy. To avoid
      this complication, close control and backup support is recommended in these
      patients.

PMID- 21184087
TI  - Intestinal transit and systemic metabolism of apple polyphenols.
AB  - BACKGROUND: Apples are the most widely consumed fruits in Germany and various
      other countries. Positive health effects of apple-derived polyphenols in vivo
      depend on their absorption, metabolism, distribution, and elimination from the
      body after consumption. Data on the metabolism of these polyphenols in humans are
      scarce. In order to study the intestinal transit and metabolism of apple
      polyphenols in humans, a variety of experiments were carried out. METHODS:
      Polyphenols were incubated with saliva (for 5 min), simulated gastric or duodenal
      juice (4 or 10 h, respectively), or rat hepatocytes (4 h) under aerobic
      conditions, and with ileostomy fluid under aerobic conditions for 10 h. The
      polyphenol profile in human serum (8 h later) and renal elimination in urine (24
      h later) were also investigated after consumption of 1 L apple juice. Polyphenols
      and their metabolites were identified and quantified by high-performance liquid
      chromatography with diode array detection (HPLC-DAD), HPLC-electrospray
      ionization-tandem mass spectrometry (ESI-MS/MS), and gas chromatography (GC)-MS.
      RESULTS: In the presence of native saliva or ileostomy fluid, beta-glycosides of
      phloretin and quercetin were hydrolyzed, to varying degrees depending on the
      sugar moiety, and to much lesser degrees in the presence of antibiotics. In the
      gastric milieu, almost complete degradation of procyanidin B(2) to (-)
      epicatechin was observed. In the presence of artificial duodenal juice flavan-3
      ol epimerization occurred. Quercetin was completely converted to phloroglucinol,
      3,4-dihydroxybenzoic acid, and 2,4,6-trihydroxybenzoic acid. Formation of
      isomeric products of hydroxycinnamic acid esters and their corresponding methyl
      esters was also observed, and similar results were obtained after incubation with
      rat hepatocytes. Products of phase II metabolism, two phloretin O-glucuronides
      and eight (methyl) quercetin O-glucuronides, were identified in the hepatocyte
      samples. Following enzymatic hydrolysis, 5-caffeoylquinic acid, 4-p
      coumaroylquinic acid, caffeic acid, (-)-epicatechin, phloretin, and quercetin
      were recovered in both serum and urine (5.3% and 3.5% of the amounts consumed,
      respectively). In addition, 19.5% of the polyphenols consumed were identified in
      the urine in the form of hydroxylated phenolic and hippuric acids. CONCLUSION:
      The findings relating to the absorption, metabolism, and systemic availability of
      polyphenols in vivo should contribute to our understanding of their biological
      effects, and the characterization of newly formed metabolites should facilitate
      further studies.

PMID- 21184088
TI  - Vitamins B status and antioxidative defense in patients with chronic hepatitis B
      or hepatitis C virus infection.
AB  - BACKGROUND & AIMS: The impact of hepatitis B virus (HBV) or hepatitis C virus
      (HCV) infection upon B vitamins status and antioxidative defense in infected
      patients was examined. METHODS: Dietary record and blood levels of B vitamins and
      oxidative stress-associated biomarkers were determined for 195 healthy controls,
      132 HBV, and 114 HCV patients. RESULTS: HBV-infected patients had significantly
      higher levels of total cholesterol, free fatty acids (FFA), and lower ghrelin
      level (p < 0.05); and HCV-infected patients had significantly higher Ishak
      inflammation score and lactate dehydrogenase activity (p < 0.05). HBV patients
      had significantly lower red blood cell (RBC) vitamins B(2) and B(6) levels, and
      HCV infection significantly decreased vitamins B(2,) B(6) and folate levels in
      RBC and/or plasma (p < 0.05). Correlation coefficients of RBC vitamin B(2) versus
      serum FFA in HBV patients, RBC vitamins B(2) and B(6) versus HCV RNA and Ishak
      inflammation score, and plasma vitamin B(6) vs Ishak inflammation score in HCV
      patients were <-0.5. HBV-infected patients had significantly higher oxidized
      glutathione level and lower glutathione peroxidase activity (p < 0.05), but HCV
      patients had significantly lower superoxide dismutase and catalase activities (p
      < 0.05). CONCLUSION: HBV or HCV infection enhanced oxidative stress and lowered B
      vitamins in circulation. In order to avoid other healthy risk, nutrition status
      should be monitored and limitation or supplementation of certain nutrients might
      be helpful for HBV- or HCV-infected patients.

PMID- 21184089
TI  - Control of cardiovascular differentiation by microRNAs.
AB  - MicroRNAs (miRs) are small non-coding RNAs, which control gene expression either
      by inducing mRNA degradation or by blocking translation, and play a crucial role
      in tissue homeostasis. In the cardiovascular system, miRs were shown to control
      cardiac hypertrophy, fibrosis and apoptosis, angiogenesis, and vessel remodeling.
      In addition, miRs regulate stem cell maintenance and some miRs induced cell fate
      decisions. This review summarizes the current insights into the control of stem
      cells and lineage commitment by miRs focusing specifically to the regulation of
      endothelial, smooth muscle, and cardiac lineage.

PMID- 21184090
TI  - The use of extracorporeal magnetic innervation for the treatment of stress
      urinary incontinence in older women: a pilot study.
AB  - PURPOSE: Stress urinary incontinence (SUI) is a major health problem that has
      substantial and important effects on health-related quality of life. In recent
      years, extracorporeal magnetic innervation (ExMI) has become a preferred method
      of treatment in urinary incontinence. This study presents the effects of ExMI
      treatment on pelvic floor muscle strength, urinary symptoms, incontinence
      conditions and quality of life of older women with SUI. METHODS: A total of 13
      patients between the ages of 61 and 69 (mean 65.23 +/- 2.8 years) were treated
      for SUI with ExMI. The following parameters were investigated: urinary symptoms,
      pelvic floor electromyographic (EMG) activity, 1-h pad test, incontinence
      conditions utilizing visual analog scale (VAS) and quality of life using Turkish
      version of the Urogenital Distress Inventory (UDI-6) and the Incontinence Quality
      of Life Instrument (I-QoL). All assessments were conducted at baseline and at the
      end of the study. Treatment lasted for 20 min, twice a week and for a total of 6
      weeks. RESULTS: The urinary symptoms and incontinence conditions decreased after
      the ExMI treatment sessions. The pad test results indicated a reduction in urine
      loss (p = 0.016). EMG values were improved (p = 0.005). Scores of I-QoL, UDI-6
      and VAS were reduced after the treatment, respectively (p = 0.002), (p = 0.002)
      and (p = 0.006). CONCLUSION: Extracorporeal magnetic innervation can be
      considered as it is an alternative, non-invasive and painless treatment method
      with good compliance for treatment of SUI in older patients.

PMID- 21184091
TI  - Congenital retroperitoneal vascular anomalies: impact on pelvic surgery.
AB  - PURPOSE: Congenital anomalies of the inferior vena cava (IVC) are not commonly
      recognized since they generally do not cause symptoms. METHODS: Preoperative
      cross-sectional imaging can identify anomalies of vascular structures that are
      highly relevant to the pelvic surgeon. The clinical impact of congenital vascular
      variations of IVC, especially on paraaortic lymphadenectomy, is investigated.
      RESULTS: In case the surgeon is unaware of these anomalies, impending
      differential diagnostic confusion (paraaortic adenopathy), intraoperative blood
      loss and the need for transfusion may occur. The development of IVC is a complex
      process concerning the formation of several anastomoses between three paired
      embryonic veins (posterior cardinal, subcardinal, supracardinal veins). In double
      IVC, the left IVC typically ends at the level of the left renal vein, in an
      anastomosis which crosses anterior to the aorta to join the normal right IVC.
      CONCLUSION: Anomalies of IVC are present in 0.4-3.5% of women. As different
      aberrations of IVC have important clinical implications, awareness of
      retroperitoneal abnormal vessels is crucial to avoid diagnostic pitfalls and
      intraoperative complications.

PMID- 21184092
TI  - Forensic and genetic characterization of mtDNA from Pathans of Pakistan.
AB  - Complete mitochondrial control region data were generated for 230 unrelated
      Pathans from North West Frontier Province and Federally Administered Tribal Areas
      of Pakistan. To confirm data quality and to explore the genetic structure of
      Pathans, mitochondrial DNA haplogroup affiliation was determined by shared
      haplogroup-specific polymorphisms in the control region and by the analysis of
      diagnostic coding region single-nucleotide polymorphisms using a multiplex system
      for the assignment of eight haplogroups: M, N1'5, W, R, R0, T, J, and U. Sequence
      comparison revealed that 193 haplotypes were defined by 215 variable sites when
      major insertions were ignored at nucleotide positions 16193, 309, and 573. From a
      phylogenetic perspective, Pathans have a heterogeneous origin, displaying a high
      percentage of West Eurasian haplogroups followed by haplogroups native to South
      Asia and a small fraction from East Asian lineages. In population comparisons,
      this ethnic group differed significantly from several other ethnic groups from
      Pakistan and surrounding countries. These results suggest that frequency
      estimates for mtDNA haplotypes should be determined for endogamous ethnic groups
      individually instead of pooling data for these subpopulations into a single
      dataset for the Pakistani population. Data presented here may contribute to the
      accuracy of forensic mtDNA comparisons in the Pathans of Pakistan.

PMID- 21184093
TI  - Development of a novel ex vivo model of corneal fungal adherence.
AB  - PURPOSE: To construct a suitable ex vivo model for the research of molecular
      mechanisms and the pharmacological screening of fungal adherence on the corneal
      surface. MATERIALS AND METHODS: Mouse eyes were divided into three groups as
      follows: a control group with normal corneal epithelium, a group with corneal
      epithelium that was needle-scarified, and a group with corneal epithelium that
      was completely debrided. All 96 corneas were placed in organ culture and
      inoculated with 5 MUl spore suspensions of Candida albicans at 109, 108, or 107
      colony-forming units (CFU)/ml and incubated for 0, 30, 60, or 120 min. The
      corneas were homogenated and diluted for quantification by counting the CFU. The
      effects of amphotericin B or chondroitin sulfate on the adherence of the fungal
      spores were evaluated with the ex vivo organ culture model and were also compared
      with the human corneal epithelium monolayer model in vitro. RESULTS: Compared
      with the normal corneas with intact epithelium, the corneas with scarified and
      debrided epithelium adhered more spores for above two and four folds. The spore
      adhesion on the corneal surface was in an inoculation concentration- and
      incubation time-dependent manner. Moreover, both amphotericin B and chondroitin
      sulfate inhibited the adhesion of C. albicans spores on the corneal surface, but
      the inhibitory rates were different between the ex vivo corneal organ culture
      model and the in vitro corneal epithelium monolayer model. CONCLUSIONS: The
      corneal organ culture was a suitable ex vivo model for the research of fungal
      adhesion mechanisms and drug screening.

PMID- 21184095
TI  - Working-memory load decreases mappings effects in spatial-compatibility tasks.
AB  - The paper investigates the role of working memory for the translation of spatial
      stimuli into spatial responses. Performance is typically superior with compatible
      mapping between stimulus and response locations than with incompatible mapping
      (spatial-mapping effect). According to popular dual-route models, the spatial
      mapping effect may arise from differences in the effectiveness of S-R
      translation, and/or from the effects of automatic response activation. Working
      memory load should not affect the automatic route, but delay S-R translation in
      the incompatible condition, increasing the mapping effect under load. These
      predictions were tested in two dual-task experiments. Participants performed a
      spatial-compatibility task with compatible or incompatible S-R mapping, while
      memorizing different amounts of spatial (Experiment 1) or verbal (Experiment 2)
      information. In both experiments, working-memory load decreased the mapping
      effect, but did not eliminate it. Results are at odds with the dual-route
      account. An alternative explanation based on the response-discrimination account
      (Ansorge and Wuhr in J Exp Psychol Hum Percept Perform 30:365-377, 2004) is
      proposed.

PMID- 21184094
TI  - Occurrence of xylan and mannan polysaccharides and their spatial relationship
      with other cell wall components in differentiating compression wood tracheids of
      Cryptomeria japonica.
AB  - Compression wood (CW) tracheids have different cell wall components than normal
      wood (NW) tracheids. However, temporal and spatial information on cell wall
      components in CW tracheids is poorly understood. We investigated the distribution
      of arabino-4-O-methylglucuronoxylans (AGXs) and O-acetyl-galactoglucomannans
      (GGMs) in differentiating CW tracheids. AGX labeling began to be detected in the
      corner of the S(1) layer at the early S(1) formation stage. Subsequently, the
      cell corner middle lamella (ccML) showed strong AGX labeling when intercellular
      spaces were not fully formed. AGX labeling was uniformly distributed in the S(1)
      layer, but showed uneven distribution in the S(2) layer. AGX labeling was mainly
      detected in the inner S(2) layer after the beginning of the helical cavity
      formation. The outer S(2) layer showed almost no labeling of low substituted
      AGXs. Only a very small amount of high substituted AGXs was distributed in the
      outer S(2) layer. These patterns of AGX labeling in the S(2) layer opposed the
      lignin and beta-1-4-galactan distribution in CW tracheids. GGM labeling patterns
      were almost identical to AGX labeling in the early stages of CW tracheids, and
      GGM labeling was detected in the entire S(2) layer from the early S(2) formation
      stage of CW tracheids with some spatial differences in labeling density depending
      on developmental stage. Compared with NW tracheids, CW tracheids showed
      significantly different AGX distributions in the secondary cell wall but similar
      GGM labeling patterns. No significant differences were observed in labeling after
      delignification of CW tracheids.

PMID- 21184096
TI  - The European eel--the swim bladder-nematode system provides a new view of the
      invasion paradox.
AB  - It is widely assumed that the likelihood of invasion decreases with increased
      species richness in the recipient community. However, the invasion paradox
      supports a negative and a positive relationship between native biodiversity and
      the success of an invader. Here, we show that for a host-parasite system
      (Anguilla anguilla as host and Anguillicoloides crassus as parasitic invader),
      invasion increases with native micro- and macroparasitic species richness. In
      fact, about 30% of the A. crassus intensity in eels could be explained by the
      number of both micro- and macroparasite species. This pattern could be due to the
      fact that A. crassus exploits a niche (the swim bladder) that is unoccupied by
      native parasite species and by the Th1/Th2 trade-off between native
      microparasites and the invader. We conclude that the host-parasite system
      resistance to invasion may depend on both niche availability and the Th1/Th2
      trade-off. As well, we encourage researchers to incorporate native parasite
      richness as a risk factor in epidemiological models of A. crassus.

PMID- 21184097
TI  - Molecular characterization, genomic distribution and evolutionary dynamics of
      Short INterspersed Elements in the termite genome.
AB  - Short INterspersed Elements (SINEs) in invertebrates, and especially in animal
      inbred genomes such that of termites, are poorly known; in this paper we
      characterize three new SINE families (Talub, Taluc and Talud) through the
      analyses of 341 sequences, either isolated from the Reticulitermes lucifugus
      genome or drawn from EST Genbank collection. We further add new data to the only
      isopteran element known so far, Talua. These SINEs are tRNA-derived elements,
      with an average length ranging from 258 to 372 bp. The tails are made up by
      poly(A) or microsatellite motifs. Their copy number varies from 7.9 * 10(3) to
      10(5) copies, well within the range observed for other metazoan genomes. Species
      distribution, age and target site duplication analysis indicate Talud as the
      oldest, possibly inactive SINE originated before the onset of Isoptera (~150 Myr
      ago). Taluc underwent to substantial sequence changes throughout the evolution of
      termites and data suggest it was silenced and then re-activated in the R.
      lucifugus lineage. Moreover, Taluc shares a conserved sequence block with other
      unrelated SINEs, as observed for some vertebrate and cephalopod elements. The
      study of genomic environment showed that insertions are mainly surrounded by
      microsatellites and other SINEs, indicating a biased accumulation within non
      coding regions. The evolutionary dynamics of Talu~ elements is explained through
      selective mechanisms acting in an inbred genome; in this respect, the study of
      termites' SINEs activity may provide an interesting framework to address the
      (co)evolution of mobile elements and the host genome.

PMID- 21184098
TI  - Comprehensive description of CFTR genotypes and ultrasound patterns in 694 cases
      of fetal bowel anomalies: a revised strategy.
AB  - Fetal bowel anomalies may reveal cystic fibrosis (CF) and the search for CF
      transmembrane conductance regulator (CFTR) gene mutations is part of the
      diagnostic investigations in such pregnancies, according to European
      recommendations. We report on our 18-year experience to document comprehensive
      CFTR genotypes and correlations with ultrasound patterns in a series of 694 cases
      of fetal bowel anomalies. CFTR gene analysis was performed in a multistep
      process, including search for frequent mutations in the parents and subsequent in
      depth search for rare mutations, depending on the context. Ultrasound patterns
      were correlated with the genotypes. Cases were distinguished according to whether
      they had been referred directly to our laboratory or after an initial testing in
      another laboratory. A total of 30 CF fetuses and 8 cases compatible with CFTR
      related disorders were identified. CFTR rearrangements were found in 5/30 CF
      fetuses. 21.2% of fetuses carrying a frequent mutation had a second rare
      mutation, indicative of CF. The frequency of CF among fetuses with no frequent
      mutation was 0.43%. Correlation with ultrasound patterns revealed a significant
      frequency of multiple bowel anomalies in CF fetuses. The results emphasize the
      need to search for rearrangements in the diagnosis strategy of fetal bowel
      anomalies. The diagnostic value of ultrasound patterns combining hyperechogenic
      bowel, loop dilatation and/or non-visualized gallbladder reveals a need to revise
      current strategies and to offer extensive CFTR gene testing when the triad is
      diagnosed, even when no frequent mutation is found in the first-step analysis.

PMID- 21184100
TI  - Enzymatic hydrolysis of cellulose in a membrane bioreactor: assessment of
      operating conditions.
AB  - The optimization of operating conditions for cellulose hydrolysis was
      systemically undertaken using an ultra-scaled down membrane bioreactor based on
      the parameter scanning ultrafiltration apparatus. The bioconversion of cellulose
      saccharification was carried out with freely suspended cellulase from Aspergillus
      niger as the biocatalyst. The polyethersulfone ultrafiltration membranes with a
      molecular weight cutoff of 10 kDa were used to construct the enzymatic membrane
      bioreactor, with the membrane showing a complete retaining of cellulase and
      cellobiase. The influence of solution pH, temperature, salt (NaCl) concentration,
      presence of cellobiase, cellulose-to-enzyme ratio and stirring speed on reducing
      sugar production was examined. The results showed that the addition of an
      appropriate amount of NaCl or cellobiase had a positive effect on reducing sugar
      formation. Under the identified optimal conditions, cellulose hydrolysis in the
      enzymatic membrane bioreactor was tested for a long period of time up to 75 h,
      and both enzymes and operation conditions demonstrated good stability. Also, the
      activation energy (E(a)) of the enzymatic hydrolysis, with a value of 34.11 +/-
      1.03 kJ mol(-1), was estimated in this study. The operational and physicochemical
      conditions identified can help guide the design and operation of enzymatic
      membrane bioreactors at the industrial scale for cellulose hydrolysis.

PMID- 21184099
TI  - Autosomal recessive hyponatremia due to isolated salt wasting in sweat associated
      with a mutation in the active site of Carbonic Anhydrase 12.
AB  - Genetic disorders of excessive salt loss from sweat glands have been observed in
      pseudohypoaldosteronism type I (PHA) and cystic fibrosis that result from
      mutations in genes encoding epithelial Na+ channel (ENaC) subunits and the
      transmembrane conductance regulator (CFTR), respectively. We identified a novel
      autosomal recessive form of isolated salt wasting in sweat, which leads to severe
      infantile hyponatremic dehydration. Three affected individuals from a small
      Bedouin clan presented with failure to thrive, hyponatremic dehydration and
      hyperkalemia with isolated sweat salt wasting. Using positional cloning, we
      identified the association of a Glu143Lys mutation in carbonic anhydrase 12
      (CA12) with the disease. Carbonic anhydrase is a zinc metalloenzyme that
      catalyzes the reversible hydration of carbon dioxide to form a bicarbonate anion
      and a proton. Glu143 in CA12 is essential for zinc coordination in this
      metalloenzyme and lowering of the protein-metal affinity reduces its catalytic
      activity. This is the first presentation of an isolated loss of salt from sweat
      gland mimicking PHA, associated with a mutation in the CA12 gene not previously
      implicated in human disorders. Our data demonstrate the importance of bicarbonate
      anion and proton production on salt concentration in sweat and its significance
      for sodium homeostasis.

PMID- 21184101
TI  - Transoral rotational esophagogastric fundoplication: technical, anatomical, and
      safety considerations.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) results primarily from the
      loss of an effective antireflux barrier, which forms a mechanical barrier against
      the retrograde movement of gastric content. Restoration of the incompetent
      antireflux barrier is possible by longitudinal and rotational advancement of the
      gastric fundus about the lower esophagus, creating an esophagogastric
      fundoplication. This article describes the technique of performing a rotational
      and longitudinal esophagogastric fundoplication, performed transorally using
      EsophyX. METHODS: The transoral incisionless fundoplication (TIF) technique
      enables the creation of a full-thickness esophagogastric fundoplication with
      fixation extending longitudinally up to 3.5 cm above the Z-line and rotationally
      more than 270 degrees around the esophagus. A key element of the technique
      involves rotating the fundus around the esophagus with a tissue mold during
      gastric desufflation. Anatomic considerations and use of the device's tissue
      invaginator to push the esophagus caudally are important to ensure safe
      positioning of the plications below the diaphragm. The steps of the technique are
      described in detail, and suggestions are given about patient selection and care,
      as well as prevention and management of complications.

PMID- 21184102
TI  - The importance of precompression time for secure stapling with a linear stapler.
AB  - BACKGROUND: One prerequisite for the safe stapling of anastomoses is the
      formation of perfectly aligned B-shaped staples. Using an animal model, this
      study investigated whether precompression enhances secure staple formation.
      METHODS: A 45-mm linear stapler with a blue cartridge (staple leg length, 3.5 mm)
      was used on three portions each of six porcine stomachs (cardia, center, and
      pylorus). Staple shape and height were examined according to the precompression
      time (0, 1, or 5 min) before firing. The shape was classified as optimal or
      suboptimal, and the heights of the staples were measured individually. The
      completeness of the proximal staple lines also was compared with the distal
      lines. RESULTS: The optimal staple rate in the 5-min group (52.7%) was
      significantly higher than in the 1-min group (28.7%; p<0.001) or the 0-min group
      (17.1%; p=0.002). The optimal staple rate in the 5-min group for the cardiac
      portion (mean wall thickness, 2.7 mm) reached 98.9%. However, this rate was less
      than 50% in the center (5.3 mm) and pylorus (4.2 mm) portions regardless of the
      precompression time. Compared with the root side, the top side of the cartridge
      had a lower optimal rate (45.3 vs. 18.7%; p<0.001). A high correlation of
      completeness was observed between the distal and proximal sides of the stump.
      CONCLUSIONS: When a linear stapling device is used, proper staple formation is
      correlated with intestinal wall thickness, and a sufficient amount of
      precompression time is effective for gaining the secure staple formation.

PMID- 21184103
TI  - Use of a peripheral venous catheter in single-incision laparoscopic surgery.
AB  - BACKGROUND: Getting the critical view in performing single-incision laparoscopic
      surgery (SILS) is challenging. In addition, visibility may be impaired by lens
      fogging and smoke accumulation in the abdomen produced by electrocautery or
      ultrasonic devices. METHODS: In 12 patients undergoing single-incision
      laparoscopic cholecystectomy, a peripheral venous catheter (PVC) was introduced
      in the right upper quadrant under direct vision, and a three-way stopcock was
      screwed onto the catheter to allow controlled smoke evacuation. Cholangiography
      was attempted in all cases, four times by introducing a (CH5) feeding tube via
      PVC. RESULTS: The described technique allowed controlled smoke evacuation via the
      PVC during SILS while reducing lens fogging and contamination by a constant air
      flow toward the venous catheter. Cholangiography was possible using a
      conventional cholangiography forceps (in 7 of 12 cases) or a feeding tube
      introduced via PVC (in 4 of 12 cases). Once, bleeding from an adjuvant vessel
      after incision of the cystic duct had to be controlled with clips, and no
      cholangiogram was achieved (in 1 of 12 cases). No procedure-related complications
      were observed. There was no conversion to conventional laparoscopic or open
      surgery. No visible scar was seen at the site of PVC introduction 5 weeks
      postoperatively. CONCLUSIONS: Visibility can be improved in SILS using a PVC
      without leaving apparent scars. Cholangiography via PVC is technically feasible
      and allows complete assessment of the biliary tract.

PMID- 21184104
TI  - Laparoendoscopic single-site (LESS) surgery versus conventional laparoscopic
      surgery: comparison of surgical port performance in a surgical simulator with
      novices.
AB  - BACKGROUND: Although laparoendoscopic single-site (LESS) surgery is feasible, it
      poses many technical challenges not seen in conventional laparoscopy. Recent
      interest and widespread implementation of LESS stems from advancements in
      commercially available access port technology. Consequently, this study
      objectively compared the technical performance between conventional laparoscopic
      and LESS surgical ports in a modified Fundamentals of Laparoscopic Surgery (FLS)
      simulator. METHODS: The 24 novice participants in this study performed the FLS
      peg transfer task using two conventional laparoscopic 12-mm working ports, the
      SILS port, the TriPort access system, and the GelPOINT system with two standard
      length 5-mm graspers. Each participant completed the task using conventional
      laparoscopy first for familiarization, followed by each of the three LESS
      surgical ports in random order. Task completion time, errors, and subjective
      questionnaire ratings were used to compare conventional laparoscopy and the
      single-port devices. Congruent with FLS scoring procedures, task completion time
      and errors were used to compute a standardized task score for each port. RESULTS:
      The task score did not differ significantly between conventional laparoscopy and
      the single-port devices. Additionally, there were no task score differences
      between trials for either the SILS port or the GelPOINT system. There was a
      significant performance decrement starting with the TriPort versus starting with
      either the SILS port or the GelPOINT, which resulted in the lowest overall trial
      task score (p<0.05). Task completion difficulty and instrument maneuverability
      resulted in no significant differences between ports. Ease of use and overall
      rank were significant, with conventional laparoscopy rated as the easiest to use
      and the highest overall followed by the GelPOINT system. CONCLUSIONS: Overall,
      the TriPort may be more challenging for novices to use in learning the LESS
      procedure than either the SILS port or the GelPOINT system. The GelPOINT system
      may offer the most consistent platform for LESS performance and novice skill
      acquisition.

PMID- 21184105
TI  - Endoscopic ultrasound-guided Trucut biopsy of gastrointestinal mesenchymal tumor.
AB  - BACKGROUND: Data on the utility of endoscopic ultrasound-guided Trucut biopsy
      (EUS-TCB) for suspected gastrointestinal mesenchymal tumor (GIMT) are limited.
      This study aimed to determine the diagnostic yield and complications from EUS-TCB
      for GIMT. METHODS: Consecutive patients with suspected upper gastrointestinal or
      rectal GIMT from the muscularis propria with a maximal diameter of 20 mm or more
      were enrolled in a prospective, single-center cohort. An EUS-TCB was performed
      when on-site fine-needle aspiration (FNA) cytology review of the lesion was
      deemed suboptimal. Gastrointestinal stromal tumor (GIST) and leiomyoma were
      defined by the presence or absence of positive immunochemistry (IC) for c-kit,
      respectively. All GIMTs with a nondiagnostic IC were considered as unspecified.
      The outcomes assessed included diagnostic pathologic and IC yield (when tested)
      and procedural complications. RESULTS: In this study, 38 patients (24 women;
      median age, 62 years) with suspected GIMT (median maximal diameter, 42 mm; range,
      20-120 mm) in the esophagus (n=6), stomach (n=28), duodenum (n=3), or rectum
      (n=1) underwent EUS-TCB without complications. Final diagnoses included GIST for
      20 patients, leiomyoma for 13 patients, unspecified GIMT for 3 patients, and
      unknown disorder for 2 patients. An EUS-FNA was performed for 33 (87%) of the 38
      patients, a diagnostic final cytology for 25 (76%) of 33 patients, and an FNA-IC
      for 12 (50%) of 24 patients. The EUS-TCB (median, 3 passes; range, 1-8 passes)
      obtained a visible tissue specimen in 37 (97%) of the 38 patients, with a median
      overall maximal fragment length of 3.5 mm (range, 0-15 mm). The diagnostic final
      TCB histology and TCB-IC were obtained, respectively, in 79 and 97% of the
      samples tested. CONCLUSIONS: In this cohort, EUS-TCB provided diagnostic
      histology and IC for 79 and 97% of the patients, respectively. For the initial
      biopsy of GIMT, EUS-TCB may be considered an acceptable alternative to EUS-FNA.

PMID- 21184106
TI  - Long-term follow-up after peroral cholangioscopy-directed lithotripsy in patients
      with difficult bile duct stones, including Mirizzi syndrome: an analysis of risk
      factors predicting stone recurrence.
AB  - BACKGROUND: Peroral cholangioscopy-directed lithotripsy (PC-directed lithotripsy)
      has been successfully used for the treatment of difficult bile duct stones,
      including Mirizzi syndrome (MS). However, long-term outcome and risk factors for
      stone recurrence after PC-directed lithotripsy have not yet been elucidated. The
      aim of this study was to assess the outcomes of long-term follow-up after PC
      directed lithotripsy and to clarify risk factors predicting stone recurrence.
      METHODS: One hundred twenty-two consecutive patients with difficult bile duct
      stones, including MS type II (McSherry classification system), were included in
      the study. RESULTS: Successful stone removal was achieved in 117 (95.9%) of the
      122 patients treated with PC-directed lithotripsy. Of these 117 patients,
      reliable follow-up information for a median period of 5.5 years (range=0.19-16.6)
      was obtained for 111 patients (94.9%) in whom stone type was classified into one
      of the following three categories: (1) MS type II (47 patients); (2) impacted
      stones (45 patients); and (3) large stones (>=20 mm in short diameter, 19
      patients). Bile duct stone recurrence was observed in 18 patients (16.1%), of
      whom 4 had MS type II, 9 had impacted stones, and 5 had large stones. Statistical
      analysis showed that dilated bile duct diameter greater than or equal to 20 mm
      was the only risk factor for stone recurrence. CONCLUSIONS: PC-directed
      lithotripsy used for the treatment of difficult bile duct stones, including MS
      type II and impacted stones, and is found to be safe at long-term follow-up.
      Dilated bile duct diameter is the only risk factor for stone recurrence. Careful
      follow-up is indispensable, particularly for patients with dilated bile ducts.

PMID- 21184107
TI  - Impact of gastrojejunostomy diameter on long-term weight loss following
      laparoscopic gastric bypass: a follow-up study.
AB  - BACKGROUND: Stenosis of the gastrojejunostomy after laparoscopic Roux-en-Y
      gastric bypass is a common occurrence. We have previously presented data
      demonstrating that the use of a 25-mm circular stapler results in a decreased
      incidence of stenosis compared to the results of a 21-mm circular stapler (6.2
      vs. 15.9%, P=0.03). One potential drawback of the larger-diameter stapler is the
      possibility for impaired long-term weight loss due to decreased restriction. We
      sought to determine the impact of circular stapler diameter on excess weight loss
      up to 5 years after surgery. METHODS: Our initial technique for creating the
      gastrojejunostomy after laparoscopic gastric bypass involved the transgastric
      passage of a 21-mm circular stapler anvil (group 1). After a large initial
      experience, we switched to a 25-mm circular stapler (group 2). Follow-up data
      were entered prospectively into a computer database. Weight loss was recorded as
      percent of excess weight lost. Only patients with follow-up beyond 3 years
      postoperatively were eligible for inclusion. RESULTS: Group 1 consisted of 145
      consecutive patients and group 2 consisted of 116 consecutive patients. There was
      no significant difference in weight loss between the groups at 3 (66.1 vs. 65.2%,
      P=0.76, n=134), 4 (66.4 vs. 58.6%, P=0.1, n=66), and 5 years after gastric bypass
      (62.7 vs. 57.5%, P=0.24, n=75). CONCLUSIONS: The use of a 25-mm circular stapler
      in laparoscopic gastric bypass operations instead of a 21-mm stapler does not
      result in significantly different long-term weight loss. The 25-mm stapler is
      preferred with our technique.

PMID- 21184108
TI  - Minimally invasive colon resection is associated with a persistent increase in
      plasma PlGF levels following cancer resection.
AB  - BACKGROUND: Minimally invasive colorectal resection (MICR) is associated with
      persistently elevated plasma VEGF levels that may stimulate angiogenesis in
      residual tumor foci. Placenta growth factor (PlGF) stimulates neovascularization
      in tumors by modulating VEGF's effects. This study's purpose was to determine the
      impact of MICR on blood PlGF levels in cancer patients (Study A) and to compare
      PreOp levels in patients with cancer and benign (BEN) disease (Study B). METHODS:
      Blood samples were collected preoperatively, on postoperative day (POD) 1, POD 3,
      and at various time points 2-4 weeks after surgery. Samples from 7-day periods
      after POD 6 were bundled to allow analysis. Plasma PlGF levels were determined
      via ELISA, results reported as mean+/-SD, and data analyzed via t test.
      Significance was set at p<0.008 after Bonferroni correction. RESULTS: Study A: 76
      colorectal cancer (CRC) patients had MICR (laparoscopic, 59%; hand-assisted,
      41%). The mean length of stay was 5.8+/-2.1 days. The mean PreOp PlGF level was
      15.4+/-4.3 pg/ml. Significantly increased levels were noted on POD 1 (25.8+/-7.7
      pg/ml, p<0.001), POD 3 (22.9+/-6.7, p<0.001), POD 7-13 (19.2+/-5.1, p<0.001), and
      POD 14-20 (19.5+/-6.7, p<0.002). The mean POD 21-27 level was not significantly
      different from baseline. Study B included 126 CRC and 111 BEN patients. PreOp
      levels were higher in the CRC patients (15.6+/-5.3 pg/ml) than in the BEN group
      (13.5+/-5.5 pg/ml, p=0.001). CONCLUSIONS: PlGF levels are elevated for 3 weeks
      after MICR and PreOp plasma levels are higher in CRC patients than in BEN disease
      patients. The cause of the postoperative increase is unclear. The persistently
      higher blood levels of PlGF and VEGF after MICR may stimulate angiogenesis in
      residual tumor foci. Further studies regarding late blood protein alterations
      after surgery appear to be indicated.

PMID- 21184109
TI  - Laparoscopic repair of suprapubic hernias: transabdominal partial extraperitoneal
      (TAPE) technique.
AB  - BACKGROUND: Suprapubic hernias are considered difficult to repair
      laparoscopically due to deficient posterior rectus sheath and proximity to
      important neurovascular structures and the urinary bladder. METHODS: We
      retrospectively reviewed 72 patients (18 males, 54 females) who, between 1998 and
      2008, had undergone laparoscopic repair for suprapubic hernial defects located
      less than 5 cm from the pubic arch. Five patients (6.9%) had recurrent hernias. A
      peritoneal flap was dissected distally to facilitate a mesh overlap of at least 5
      cm from the hernial defect. The lower margin of the mesh was fixed under direct
      vision to Cooper's ligaments bilaterally. The raised peritoneal flap was
      reattached to the anterior abdominal wall thereby partially extraperitonealizing
      the mesh. RESULTS: Mean diameter of the hernial defect was 5.2 cm (range=3.1-7.3
      cm) as measured intraperitoneally. Mean size of the mesh used was 328.8 cm2
      (range=225-506 cm2). Mean operating time was 116 min (range=64-170 min). Overall
      complication rate was 27.8%. There were no conversions. No recurrences were
      observed at a mean follow-up of 4.8 years (range=1.2-6.9 years) and a follow-up
      rate of 84.7% CONCLUSION: A mesh overlap of at least 5 cm and fixation of the
      lower margin of the mesh under direct vision to Cooper's ligaments appears to
      confer increased strength and durability and contribute to low hernia recurrence
      rates in patients with suprapubic hernias.

PMID- 21184110
TI  - Robotic suturing on the FLS model possesses construct validity, is less
      physically demanding, and is favored by more surgeons compared with laparoscopy.
AB  - BACKGROUND: The value of robotic assistance for intracorporeal suturing is not
      well defined. We compared robotic suturing with laparoscopic suturing on the FLS
      model with a large cohort of surgeons. METHODS: Attendees (n=117) at the SAGES
      2006 Learning Center robotic station placed intracorporeal sutures on the FLS box
      trainer model using conventional laparoscopic instruments and the da Vinci(r)
      robot. Participant performance was recorded using a validated objective scoring
      system, and a questionnaire regarding demographics, task workload, and suturing
      modality preference was completed. Construct validity for both tasks was assessed
      by comparing the performance scores of subjects with various levels of
      experience. A validated questionnaire was used for workload measurement. RESULTS:
      Of the participants, 84% had prior laparoscopic and 10% prior robotic suturing
      experience. Within the allotted time, 83% of participants completed the suturing
      task laparoscopically and 72% with the robot. Construct validity was demonstrated
      for both simulated tasks according to the participants' advanced laparoscopic
      experience, laparoscopic suturing experience, and self-reported laparoscopic
      suturing ability (p<0.001 for all) and according to prior robotic experience,
      robotic suturing experience, and self-reported robotic suturing ability (p<0.001
      for all), respectively. While participants achieved higher suturing scores with
      standard laparoscopy compared with the robot (84+/-75 vs. 56+/-63, respectively;
      p<0.001), they found the laparoscopic task more physically demanding (NASA score
      13+/-5 vs. 10+/-5, respectively; p<0.001) and favored the robot as their method
      of choice for intracorporeal suturing (62 vs. 38%, respectively; p<0.01).
      CONCLUSIONS: Construct validity was demonstrated for robotic suturing on the FLS
      model. Suturing scores were higher using standard laparoscopy likely as a result
      of the participants' greater experience with laparoscopic suturing versus robotic
      suturing. Robotic assistance decreases the physical demand of intracorporeal
      suturing compared with conventional laparoscopy and, in this study, was the
      preferred suturing method by most surgeons. Curricula for robotic suturing
      training need to be developed.

PMID- 21184112
TI  - Abnormal glucose tolerance testing following gastric bypass demonstrates reactive
      hypoglycemia.
AB  - BACKGROUND: Symptoms of reactive hypoglycemia have been reported by patients
      after Roux-en-Y gastric bypass (RYGB) surgery who experience maladaptive eating
      behavior and weight regain. A 4-h glucose tolerance test (GTT) was used to assess
      the incidence and extent of hypoglycemia. METHODS: Thirty-six patients who were
      at least 6 months postoperative from RYGB were administered a 4-h GTT with
      measurement of insulin levels. Mean age was 49.4+/-11.4 years, mean preoperative
      body mass index (BMI) was 48.8+/-6.6 kg/m2, percent excess BMI lost (%EBL) was
      62.6 +/- 21.6%, mean weight change from nadir weight was 8.2+/-8.6 kg, and mean
      follow-up time was 40.5+/-26.7 months. Twelve patients had diabetes
      preoperatively. RESULTS: Thirty-two of 36 patients (89%) had abnormal GTT. Six
      patients (17%) were identified as diabetic based on GTT. All six of these
      patients were diabetic preoperatively. Twenty-six patients (72%) had evidence of
      reactive hypoglycemia at 2 h post glucose load. Within this cohort of 26
      patients, 14 had maximum to minimum glucose ratio (MMGR)>3:1, 5 with a ratio>4:1.
      Eleven patients had weight regain greater than 10% of initial weight loss (range
      4.9-25.6 kg). Ten of these 11 patients (91%) with weight recidivism showed
      reactive hypoglycemia. CONCLUSIONS: Abnormal GTT is a common finding post RYGB.
      Persistence of diabetes was noted in 50% of patients with diabetes
      preoperatively. Amongst the nondiabetic patients, reactive hypoglycemia was found
      to be more common and pronounced than expected. Absence of abnormally high
      insulin levels does not support nesidioblastosis as an etiology of this
      hypoglycemia. More than 50% of patients with reactive hypoglycemia had
      significantly exaggerated MMGR. We believe this may be due to the nonphysiologic
      transit of food to the small intestine due to lack of a pyloric valve after RYGB.
      This reactive hypoglycemia may contribute to maladaptive eating behaviors leading
      to weight regain long term. Our data suggest that GTT is an important part of
      post-RYGB follow-up and should be incorporated into the routine postoperative
      screening protocol. Further studies on the impact of pylorus preservation are
      necessary.

PMID- 21184113
TI  - Laparoscopic proctectomy after neoadjuvant therapy: safety and long-term follow
      up.
AB  - PURPOSE: The oncologic value of laparoscopic proctectomy for rectal
      adenocarcinoma is uncertain. Long-term data, particularly in tumors at higher
      risk of recurrence, is lacking. This study evaluated short- and long-term
      outcomes in patients who underwent laparoscopic proctectomy for locally advanced
      cancer (transmural and/or node positive) after neoadjuvant chemoradiotherapy
      (CRT). METHODS: This is a retrospective cohort study of 50 consecutive patients
      with transmural and/or node-positive rectal cancer, from a single surgeon's
      practice, from 2001 to 2009. All patients were treated with neoadjuvant CRT. All
      cases were started laparoscopic or hand-assist. RESULTS: Of 50 patients, 58% were
      men, mean age was 60.9 years, and mean body mass index (BMI) was 26.3. The
      average distance of the tumor from the anal verge was 5.7 cm. All patients
      completed CRT, and the subsequent mean time to operation was 7.8 weeks. The
      conversion to open rate was 26%. Thirty-day mortality was 2%. Twenty-two percent
      had a complete response to CRT. Two patients had positive margins: one developed
      distant recurrence only, and the other died 2 years later without evidence of
      local recurrence. The average distal margin was 3.26 cm. The average lymph nodes
      resected was 11.9. Seven patients had an ileus that delayed discharge and one had
      a pelvic abscess. Median length of stay was 6 days. Three patients were
      readmitted within 30 days; all for dehydration. Mean follow-up was 2.72 years.
      According to Kaplan-Meier analysis, the 5-year local recurrence rate was 9.6%,
      and the distant recurrence rate was 31%. Five-year disease-specific survival was
      80% and overall survival was 68%. CONCLUSIONS: Patients with locally advanced
      rectal cancer treated with neoadjuvant therapy can safely undergo laparoscopic
      proctectomy with a low rate of complications. Oncologic outcomes, including 5
      year disease-free survival and local recurrence rates, are comparable to
      published reports of open proctectomy.

PMID- 21184114
TI  - Transgastric small bowel resection and anastomosis: a survival study.
AB  - BACKGROUND: Recently, natural orifice transluminal endoscopic surgery has emerged
      with new ideas of a transgastric access. The authors have evaluated the
      possibility of transgastric bowel resection with several modifications. This
      study aimed to evaluate transgastic small bowel resection using an automated
      stapling device via an assisting trocar. In a survival experiment, the possible
      technical problems, medical complications, and safety of the procedure were
      investigated as well as the postoperative course and follow-up care. METHODS: The
      study protocol was submitted to the animal research committee and approved. A
      total of 13 swine with a body weight of 25 kg (range, 20-46 kg) were investigated
      and entered into the study. General anesthesia was induced by certified personnel
      using ketamine, halothan, oxygen, and nitrous oxide. One trocar was used for
      laparoscopic assistance. A needleknife was used to complete a 1.5-cm-long
      gastrotomy. The gastroscope was advanced into the peritoneal cavity, and a small
      bowel loop was identified. Through the second channel of the scope, a coag
      grasper was used to dissect the mesentery. A linear stapler was inserted through
      the assisting trocar, and the resection was performed. Afterward, the bowel ends
      were reopened, and the stapler was reinserted for a side-to-side anastomosis. The
      specimen was removed via the stomach. Gastric closure was completed using
      laparoscopic mini-instruments. All problems were prospectively documented. Follow
      up evaluation was performed over 2 weeks. The animals were killed and reopened,
      and evidence of adhesions, infection, and abscess formation was evaluated.
      RESULTS: In this study, 13 female animals with a body weight of 25 kg (range, 20
      46 kg) underwent surgery. No mortality or postoperative complications occurred.
      The animals had stable weight development. After a follow-up period of 2 weeks,
      the animals were killed. The findings included minor adhesions, no abscess, and
      no inflammation. CONCLUSION: Transgastric bowel resection with minor laparoscopic
      assistance is a safe experimental procedure when performed by surgeons with
      adequate and extensive training. These experimental procedures should be
      evaluated carefully and critically in clinical practice.

PMID- 21184115
TI  - Metaanalysis of trials comparing minimally invasive and open distal
      pancreatectomies.
AB  - BACKGROUND: The current literature suggests that minimally invasive distal
      pancreatectomy (MIDP) is associated with faster recovery and less morbidity than
      open surgery. However, most studies have been limited by a small sample size and
      a single-institution design. To overcome this problem, the first metaanalysis of
      studies comparing MIDP and open distal pancreatectomy (ODP) has been performed.
      METHODS: A systematic literature review was conducted to identify studies
      comparing MIDP and ODP. Perioperative outcomes (e.g., morbidity and mortality,
      pancreatic fistula rates, blood loss) constituted the study end points.
      Metaanalyses were performed using a random-effects model. RESULTS: For the
      metaanalysis, 10 studies including 349 patients undergoing MIDP and 380 patients
      undergoing ODP were considered suitable. The patients in the two groups were
      similar with respect to age, body mass index (BMI), American Society of
      Anesthesiology (ASA) classification, and indication for surgery. The rate of
      conversion from full laparoscopy to hand-assisted procedure was 37%, and that
      from minimally invasive to open procedure was 11%. Patients undergoing MIDP had
      less blood loss, a shorter time to oral intake, and a shorter postoperative
      hospital stay. The mortality and reoperative rates did not differ between MIDP
      and ODP. The MIDP approach had fewer overall complications [odds ratio (OR),
      0.49; 95% confidence interval (CI), 0.27-0.89], major complications (OR, 0.57;
      95% CI, 0.34-0.96), surgical-site infections (OR, 0.32; 95% CI, 0.19-0.53), and
      pancreatic fistulas (OR, 0.68; 95% CI, 0.47-0.98). CONCLUSIONS: The MIDP
      procedure is feasible, safe, and associated with less blood loss and overall
      complications, shorter time to oral intake, and shorter postoperative hospital
      stay. Furthermore, the minimally invasive approach reduces the rate of pancreatic
      leaks and surgical-site infections after ODP.

PMID- 21184116
TI  - Consensus statement on the adoption of the COPE guidelines.

PMID- 21184117
TI  - Effects of dark septate endophytes on tomato plant performance.
AB  - Non-mycorrhizal fungal root endophytes can be found in all natural and cultivated
      ecosystems, but little is known about their impact on plant performance. The
      impact of three mitosporic dark septate endophytes (DSE48, DSE49 and
      Leptodontidium orchidicola) on tomato plant characteristics was studied. Their
      effects on root and shoot growth, their influence on fruit yield and fruit
      quality parameters and their ability to diminish the impact of the pathogen
      Verticillium dahliae were investigated. While shoot biomass of young plants was
      enhanced between 10% and 20% by the endophytes DSE48 and L. orchidicola in one of
      two experiments and by DSE49 in both experiments, vegetative growth parameters of
      24-week-old plants were not affected except a reproducible increase of root
      diameter by the isolate DSE49. Concerning fruit yield and quality, L. orchidicola
      could double the biomass of tomatoes and increased glucose content by 17%, but
      this was dependent on date of harvest and on root colonisation density.
      Additionally, the endophytes DSE49 and L. orchidicola decreased the negative
      effect of V. dahliae on tomato, but only at a low dosage of the pathogen. This
      indicates that the three dark septate endophytes can have a significant impact on
      tomato characters, but that the effects are only obvious at early stages of
      vegetative and generative development and currently too inconsistent to recommend
      the application of these DSEs in horticultural practice.

PMID- 21184118
TI  - General anaesthesia for deep brain stimulator electrode insertion in Parkinson's
      disease.
AB  - BACKGROUND: This paper compares the use of general and local anaesthetic in
      patients having deep brain stimulator (DBS) surgery. It is a retrospective case
      note study of 46 patients treated consecutively with subthalamic nucleus
      stimulation for Parkinson's disease as practise changed in a Neurosurgical unit.
      METHODS: The first 20 patients (LA group) had permanent electrodes placed under
      local anaesthesia. The remaining 26 patients (GA group) had the entire procedure
      under general anaesthesia. The groups were similar for age, sex, duration of
      Parkinson's disease and preoperative levodopa requirement. RESULTS: The clinical
      results were similar in that within each group, the reduction in levodopa was not
      only clinically but also statistically significant (p < 0.001 for both, paired t
      test): for the LA group, the 6-month requirement was 39.4% (29.5-52.6%) of the
      preoperative requirement and for the GA group, the 6-month requirement was 32.3%
      (25.2-41.5%) of the preoperative requirement. The reduction in levodopa was
      maintained at 1 year. Of note, duration of surgery and length of stay were
      reduced. The mean duration of surgery was 8.2 h (7.8-8.6) for the LA group and
      7.5 h (7.2-7.8) for the GA group (p = 0.003). The geometric mean of length of
      hospital stay was 5.4 days(4.6-6.3) for the LA group and 3.8 days (3.4-4.4) for
      the GA group (p = 0.001) There was no difference in electrophysiological
      recording. CONCLUSION: This study describes benefits in the GA group for the
      entire procedure of STN DBS. In these samples, there was no difference in the
      adverse effects seen in patients undergoing deep brain stimulator insertion with
      general anaesthetic compared with local anaesthetic. The use of general
      anaesthetic did not detract from the known benefits of surgery.

PMID- 21184119
TI  - The knockdown of Ha-GRIM-19 by RNA interference induced programmed cell death.
AB  - GRIM-19 (genes associated with retinoid-IFN-induced mortality-19) is a subunit of
      mitochondrial respiratory complex I in mammalian systems. However, its function
      in vivo is not really understood. We cloned GRIM-19 and explored its function and
      hormonal regulation in insect, the cotton bollworm, Helicoverpa armigera. The
      results showed that Ha-GRIM-19 was highly expressed during the larval stage. Its
      transcript levels could be upregulated by juvenile hormone (JH) analog methoprene
      or by methoprene plus 20E. The methoprene-upregulated transcription enhancement
      of Ha-GRIM-19 was mediated by the transcription factor Ha-Met1, the putative
      receptor of JH. Other transcription factors Ha-USP1 and Ha-Br-Z2 suppressed the
      action of methoprene in inducing Ha-GRIM-19 expression, but Ha-Br-Z2 introduced
      interaction between 20E and methoprene in upregulation of Ha-GRIM-19. The
      knockdown of Ha-GRIM-19 by RNA interference in larvae and in insect cell line
      induced programmed cell death. These data imply that Ha-GRIM-19 plays role in
      keeping the normal cellular growth and it is able to be upregulated by methoprene
      through putative JH receptor Met.

PMID- 21184121
TI  - Chemosynthetic activity prevails in deep-sea sediments of the Central Indian
      Basin.
AB  - It is hypothesized that in the deep-sea, under psychrophilic, barophilic and
      oligotrophic conditions, microbial community of Central Indian Basin (CIB)
      sediments could be chemosynthetic. In the dark, at near ambient temperature, 4 +/
      2 degrees C, 500 atm pressure, pelagic red clay could fix carbon at rates
      ranging from 100 to 500 nmol C g(-1) dry wt day(-1). These clays accumulate in
      the deepest and the most remote areas of the ocean and contain <30% biogenic
      material. These clays with volcanic signatures fixed 230-9,401 nmol C g(-1) dry
      wt day(-1) while siliceous radiolarian oozes of the basin fixed only 5-45 nmol C
      g(-1) dry wt day(-1). These rates are comparable to those of white smoker waters
      and are 1-4 orders of magnitude less than those of bacterial mats and active
      vents recorded at other localities worldwide. The experimental ratios of carbon
      fixation to metal oxidation in the sediments were 0-1 order of magnitude higher
      than the corresponding average theoretical ratio of 0.0215 (0.0218, 0.0222,
      0.0207 and 0.0211 for Fe, Mn, Co and Ni, respectively) in the siliceous ooze. In
      case of pelagic red clay it was 0-2 orders higher than theoretical ratio. Thus,
      chemosynthetic activity could be more widespread, albeit at low rates, than
      previously considered for abyssal basins. These environments may be dependent
      partially or even wholly on in situ microbial primary production for their carbon
      requirements rather than on photosynthetically derived detritus from surface
      waters.

PMID- 21184122
TI  - Influence of distal and proximal cues in encoding geometric information.
AB  - Vertebrates use geometric and featural information for spatial navigation. When
      both geometric and featural cues are available, animals can use a variety of
      spatial strategies based on this information. To examine the nature of these
      strategies, we manipulated the spatial relationship between a conspicuous cue and
      the position of the goal when goldfish (Carassius auratus) were searching for the
      exit of a rectangular environment with one distinctive wall. Two groups of fish
      were used, one with the distinctive wall close to the goal and the other with the
      distinctive wall on the other end of the enclosure. Results showed that fish
      encoded featural and geometric information in both conditions but the spatial
      relationship between the goal and the distinctive wall influences the
      characteristics of the encoding of the spatial cues and the strategy used to
      locate the goal. These results suggest that fish in both procedures use the local
      featural cues associated with the goal instead of the whole set of spatial cues
      as previous studies propose.

PMID- 21184123
TI  - Spatial behavior: the impact of global and local geometry.
AB  - Humans and other animals use the global geometry of the surrounding environment
      in order to orient and determine which direction they are facing. Accordingly,
      the impact of environment geometry on spatial behavior is reflected in the paths
      of progression in the environment. When the perception of the global geometry is
      limited, such as in large or dark environments, the global geometry of the
      environment has to be constructed gradually as the accumulated geometry of
      locales. In the present study, we progressively altered the form of a dark square
      test arena by means of local alterations to its corners and walls, in order to
      differentiate the impact of the global arena geometry from that of the local
      arena geometry sectors on spatial behavior in rats. We found that as long as the
      local alterations did not distort the global square geometry of the dark
      environment, the rats' behavior did not significantly change. In contrast,
      distortion of the square shape of the arena resulted in significant changes in
      the spatial distribution of the rats' activity. Accordingly, we suggest that the
      perceived global geometry affects spatial behavior, overriding the impact of the
      local geometry.

PMID- 21184124
TI  - New Caledonian crows use tools for non-foraging activities.
AB  - Tool use is of great interest for cognitive research, largely because it can be
      particularly revealing about the underlying information processing mechanisms.
      Tool use that is inflexible or requires extensive experience to change, and that
      is only addressed towards specific targets such as food, is not likely to reflect
      unusual or particularly complex cognition. On the contrary, if tools are employed
      flexibly and for a variety of innovative purposes, then conventional combinations
      of inherited predispositions and associative learning are challenged and
      interesting questions emerge. Since New Caledonian crows (Corvus moneduloides)
      are especially adept at using and making tools for food extraction, we decided to
      examine their ability to generalise this to other contexts. We recorded how five
      pairs of New Caledonian crows interacted with novel objects that were not
      associated with food. We observed eight occasions in which the first contact with
      the novel object was mediated by a tool, suggesting that the function of the tool
      was for exploration. This is the first report of non-foraging tool use in New
      Caledonian crows, and it implies that the cognitive operations controlling tool
      oriented behaviour in this species are more general than previously thought.

PMID- 21184125
TI  - Sequential planning in rhesus monkeys (Macaca mulatta).
AB  - In the current study, we examined the planning abilities of rhesus monkeys
      (Macaca mulatta) by training them on a five-item list composed of coloured
      photographs and then testing them on switch and mask trials. In contrast to
      previous studies where monkeys made responses using a joystick, in the current
      study, monkeys made responses directly to a touch screen. On switch trials, after
      a response to the first list item, the on-screen positions of two list items were
      exchanged. Performance on trials in which the second and third list items were
      exchanged was poorer compared to normal (non-switch) trials for all subjects.
      When the third and fourth items were exchanged, however, only one subject
      continued to show performance deficits. On mask trials, following a response to
      the first item, the remaining items were covered by opaque white squares. When
      two items were masked, all four subjects responded to each masked item at a level
      significantly above chance. When three items were masked, however, only one
      subjected was able to respond to all three masked items at a level significantly
      above chance. The results of the present study indicate that three of our four
      monkeys planned one response ahead while a single monkey planned two responses
      ahead. The significance of these findings is discussed in relation to previous
      studies on planning in chimpanzees and monkeys.

PMID- 21184126
TI  - Impaired antibody response to conjugated meningococcal serogroup C vaccine in
      asplenic patients.
AB  - The purpose of this study was to determine the quantity and quality of antibodies
      against the meningococcal serogroup C (MenC) conjugated vaccine in asplenic
      patients. In 116 asplenic patients, antibody concentrations (IgG) were measured
      against meningococcal serogroup C before and after immunisation. Of MenC-specific
      IgG, both antibody avidity and subclasses of IgG1 and IgG2 were determined. The
      mean MenC IgG concentration rose from 0.16 MUg/mL prior to vaccination to 3.69
      MUg/mL 3 weeks post-vaccination, with 67% of patients reaching the threshold of
      >= 2.0 MUg/mL. The mean IgG concentration at 35 weeks post-vaccination was 3.10
      MUg/mL. IgG2 concentrations increased more than IgG1. Marginal avidity maturation
      was seen. Hypo-responders to the first MenC vaccine (IgG anti-MenC <= 2.0 MUg/mL)
      were offered a booster dose. After revaccination, 59% reached the chosen IgG
      threshold. The IgG concentration rose from 0.29 to 1.12 MUg/mL, with an increase
      in the IgG1/IgG2 ratio. Avidity indices remained below 33%. In asplenic patients,
      the quantity and quality of antibodies produced after one dose of conjugated MenC
      vaccination is lower than that observed in previous studies in healthy adults.
      Booster vaccination does, indeed, lead to a rise in IgG geometric mean
      concentrations (GMCs), but does not lead to higher avidity of antibodies.

PMID- 21184127
TI  - Low-level laser therapy (LLLT) acts as cAMP-elevating agent in acute respiratory
      distress syndrome.
AB  - The aim of this work was to investigate if the low-level laser therapy (LLLT) on
      acute lung inflammation (ALI) induced by lipopolysaccharide (LPS) is linked to
      tumor necrosis factor (TNF) in alveolar macrophages (AM) from bronchoalveolar
      lavage fluid (BALF) of mice. LLLT has been reported to actuate positively for
      relieving the late and early symptoms of airway and lung inflammation. It is not
      known if the increased TNF mRNA expression and dysfunction of cAMP generation
      observed in ALI can be influenced by LLLT. For in vivo studies, Balb/c mice (n =
      5 for group) received LPS inhalation or TNF intra nasal instillation and 3 h
      after LPS or TNF-alpha, leukocytes in BALF were analyzed. LLLT administered
      perpendicularly to a point in the middle of the dissected bronchi with a
      wavelength of 660 nm and a dose of 4.5 J/cm(2). The mice were irradiated 15 min
      after ALI induction. In vitro AM from mice were cultured for analyses of TNF mRNA
      expression and protein and adenosine3':5'-cyclic monophosphate (cAMP) levels. One
      hour after LPS, the TNF and cAMP levels in AM were measured by ELISA. RT-PCR was
      used to measure TNF mRNA in AM. The LLLT was inefficient in potentiating the
      rolipram effect in presence of a TNF synthesis inhibitor. LLLT attenuated the
      neutrophil influx and TNF in BALF. In AM, the laser increased the cAMP and
      reduced the TNF-alpha mRNA. LLLT increases indirectly the cAMP in AM by a TNF
      dependent mechanism.

PMID- 21184129
TI  - Black tea polyphenol theaflavin suppresses LPS-induced ICAM-1 and VCAM-1
      expression via blockage of NF-kappaB and JNK activation in intestinal epithelial
      cells.
AB  - OBJECTIVE: The aim of this study was to determine the impact of the black tea
      polyphenol, theaflavin, on the expression of adhesion molecules and activation of
      lipopolysaccharide (LPS)-induced innate signaling in rat intestinal epithelial
      (RIE) cells. METHODS: The effect of theaflavin on neutrophil adhesion, expression
      of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule
      (VCAM)-1, LPS-induced nuclear factor-kappa B (NF-kappaB), and mitogen-activated
      protein kinase (MAPK) signaling was examined by neutrophil adhesion assay, RT
      PCR, Western blotting, immunofluorescence, and electrophoretic mobility shift
      assay (EMSA). RESULTS: Theaflavin suppressed adhesion of neutrophils to LPS
      stimulated RIE cells. LPS-induced ICAM-1 and VCAM-1 expressions were inhibited by
      theaflavin. LPS-induced IkappaBalpha phosphorylation/degradation and nuclear
      translocation of NF-kappaB/p65 were blocked by theaflavin. Also, theaflavin
      blocked NF-kappaB DNA-binding activity in EMSA. LPS-induced phosphorylation of
      JNK was inhibited by theaflavin. Bay11-7082 (a NF-kappaB inhibitor) and SP600125
      (a JNK inhibitor) suppressed the LPS-induced ICAM-1 and VCAM-1 mRNA
      accumulations. CONCLUSIONS: These results indicate that black tea polyphenol
      theaflavin suppresses LPS-induced ICAM-1 and VCAM-1 expressions through blockage
      of NF-kappaB and JNK activation in intestinal epithelial cells.

PMID- 21184130
TI  - Cross-linking of CD137 ligand modulates immune responses of thioglycollate
      elicited mouse peritoneal macrophages.
AB  - OBJECTIVE: The aim of this study was to investigate effects of CD137 ligand
      (CD137L)-mediated reverse signaling on cellular responses in thioglycollate
      elicited mouse peritoneal macrophages. METHODS: Five-week-old male C57B6 mice
      were injected intraperitoneally with thioglycollate for 3 days to isolate
      peritoneal macrophages. We counted total cell numbers with a Cell Lab Quanta SC.
      CD137L expression was examined with a flow cytometer. We also measured expression
      of inflammatory cytokines by flow cytometry and/or real time-PCR. RESULTS: Cross
      linking of CD137L with recombinant CD137-Fc protein (rCD137-Fc) increased total
      numbers of thioglycollate-elicited mouse peritoneal macrophages (hIgG-Fc- vs.
      rCD137-Fc-treated group, p < 0.05). However, ligation reduced the increase in IL
      1beta and IL-6 levels. Real-time PCR analysis showed that treatment of cells with
      rCD137-Fc also reduced transcript levels of IL-1beta, IL-6, iNOS and COX2 (hIgG
      Fc- vs. rCD137-Fc-treated group, p < 0.05), as well as expression of CD137L.
      CONCLUSION: Reverse signals initiated by CD137L negatively modulate certain
      immune functions of thioglycollate-elicited peritoneal macrophages.

PMID- 21184128
TI  - Role of xenobiotic metabolism in cancer: involvement of transcriptional and miRNA
      regulation of P450s.
AB  - Cytochrome P450 enzymes (P450s) are important targets in cancer, due to their
      role in xenobiotic metabolism. Since P450s are the "bridges" between the
      environment and our body, their function can be linked in many ways to
      carcinogenesis: they activate dietary and environmental components to ultimate
      carcinogens (i), the cancer tissue maintains its drug resistance with altered
      expression of P450s (ii), P450s metabolize (sometimes activate) drugs used for
      cancer treatment (iii) and they are potential targets for anticancer therapy
      (iiii). These highly polymorphic enzymes are regulated at multiple molecular
      levels. Regulation is as important as genetic difference in the existing
      individual variability in P450 activity. In this review, examples of the
      transcriptional (DNA methylation, histone modification, modulation by
      xenosensors) and post-transcriptional (miRNA) regulation will be presented and
      thereby introduce potential molecular targets at which the metabolism of
      anticancer drugs, the elimination of cancerogenes or the progress of
      carcinogenesis could be affected.

PMID- 21184131
TI  - New vandetanib analogs: fused tricyclic quinazolines with antiangiogenic
      potential.
AB  - The antiangiogenic effects of three novel anilinoquinazoline derivatives were
      studied with the aim to find new multi-kinase inhibitors as anticancer agents.
      The compounds are characterized by dioxolane, dioxane and dioxepine rings and
      bear the same aniline substituent in 4 position as vandetanib, known
      antiangiogenic agent. The in vitro assays were carried out on human umbilical
      vein endothelial cells (HUVECs), whereas in vivo angiogenesis was evaluated by
      means of Matrigel plug assay. The results showed that these compounds exert, even
      though to different extents, antiangiogenic activity affecting the various step
      of the process that leads to the formation of new blood vessels. At high
      concentrations they induced antiproliferative effects, whereas at non-cytotoxic
      concentrations they inhibited cell migration and the formation of tubular
      structures in Matrigel. In in vitro assays the dioxolane derivative 1 was more
      effective than vandetanib. Indeed, it inhibited the effects induced by exogenous
      VEGF and FGF-2 on both cell proliferation and morphogenesis, whereas vandetanib
      was completely ineffective. Moreover, all the compounds, as vandetanib,
      counteracted the FGF-2-induced increase in the hemoglobin content in the Matrigel
      plugs. Our results showed that all the three novel derivatives possess both in
      vitro and in vivo antiangiogenic activity, with compound 1 more effective than
      vandetanib to inhibit in vitro angiogenesis induced by exogenous cytokines.

PMID- 21184133
TI  - NGAL and NGALR are frequently overexpressed in human gliomas and are associated
      with clinical prognosis.
AB  - Recently, neutrophil gelatinase-associated lipocalin (NGAL) and its cell surface
      receptor, NGALR, have been shown to have critical roles in the biology of various
      tumors. Therefore, we investigated the expression of NGAL and NGALR in tumor
      sections obtained from patients with gliomas, and compared these results with the
      clinical characteristics of the patients. Using immunohistochemical assays, the
      expression levels of NGAL and NGALR were found to be up-regulated in tumor
      tissues, and to be related to tumor grade (p < 0.001). A positive correlation
      between expression of the two markers was also observed in these assays (r =
      0.849; p < 0.001). Overexpression of NGAL and NGALR in glioma tissues was also
      confirmed in western blot analysis and real-time quantitative RT-PCR assays.
      Furthermore, overexpression of NGAL and NGALR was found to be significantly
      associated with poor prognosis (p < 0.001 in each case). Multivariate analysis
      identified patient age, tumor grade, and expression levels of NGAL and NGALR to
      be independent prognostic factors. In particular, NGAL(2+)/NGALR(2+) tissues were
      associated with lower rates of survival (risk ratio, 1.378; 95% CI, 1.102-1.724;
      p = 0.005). These findings suggest that NGAL and NGALR expression are frequently
      up-regulated in gliomas, and are closely associated with poor clinical outcome.

PMID- 21184134
TI  - Performance of microbial fuel cell with volatile fatty acids from food wastes.
AB  - Food wastes were used as feedstock for the direct production of electricity in a
      microbial fuel cell (MFC). MFC operations with volatile fatty acids (VFA)
      produced 533 mV with a maximum power density of 240 mW/m(2). Short-chain VFAs,
      such as acetate, were degraded more rapidly and thus supported higher power
      generation than longer chain ones. In general, the co-existence of other,
      different VFAs slowed the removal of each VFA, which indicated that anodic
      microbes were competing for different substrates. 16S rRNA gene analysis using
      PCR-DGGE indicated that the MFC operation with VFAs had enriched unique microbial
      species.

PMID- 21184135
TI  - Nisin-selectable food-grade secretion vector for Lactococcus lactis.
AB  - A nisin-resistant Lactococcus lactis strain TML01 was isolated from crude milk. A
      gene with 99% homology to the nisin-resistance gene, nsr, was identified. The
      food-grade secretion plasmid, pLEB690 (3746 bp), was constructed based on this
      novel nsr gene enabling primary selection with up to 5 MUg nisin/ml. The
      functionality of pLEB690 as a secretion vector was shown by expressing and
      secreting the pediocin AcH gene papA in L. lactis. pLEB690 is therefore, a
      functional food-grade secretion vector potentially useful for the food industry.

PMID- 21184132
TI  - CD133+ niches and single cells in glioblastoma have different phenotypes.
AB  - Putative CD133(+) brain tumor stem cells have been shown to be located in niches
      and as single cells. This is the first study providing insight into the different
      phenotypes of CD133(+) cells in glioblastoma according to localization. Paraffin
      sections were stained by double immunofluorescence with CD133 and the candidate
      stem cell markers Sox2, Bmi-1, EGFR, podoplanin and nestin, the proliferation
      marker Ki67 and the endothelial cell markers CD31, CD34, and VWF. Cell counting
      showed that the CD133(+) cells in the niches had a significantly higher
      expression of Sox2, EGFR and nestin compared to CD133(+) single cells, but only a
      3% Ki67 labeling index versus 14% found for CD133(+) single cells. Only low
      endothelial cell marker expression was found in the niches or the CD133(-) tumor
      areas, while 43% CD133(+)/CD31(+) and 25% CD133(+)/CD34(+) single cells were
      found. CD133(+) blood vessels within CD133(+) niches were less proliferative and
      more often Bmi-1(+) than CD133(+) blood vessels outside niches. In conclusion,
      different CD133(+) cell phenotypes exist according to the in situ localization,
      and also the phenotype of CD133(+) blood vessels vary according to the
      localization. CD133(+) niches contain stem-like cells with a lower proliferation
      index than CD133(+) single cells, which have an endothelial differentiation
      profile suggesting a role in angiogenesis.

PMID- 21184136
TI  - Transgenic silkworms that weave recombinant proteins into silk cocoons.
AB  - As a result of breeding for more than 4,000 years, the silkworm, Bombyx mori, has
      acquired the ability to synthesize bulk amounts of silk proteins in its silk
      glands. To utilize this capacity for mass production of useful proteins,
      transgenic silkworms were generated that synthesized recombinant proteins in the
      silk gland and secreted them into the silk cocoon. The silk gland is classified
      into two main regions: the posterior (PSG) and the middle silk gland (MSG). By
      controlling the expressed regions of the recombinant protein gene in the silk
      gland, we were able to control the localization of the synthesized protein in the
      silk thread. Expression in the PSG or MSG led to localization in the insoluble
      fibroin core or hydrophilic outer sericin layer, respectively. This review
      focuses on the expression of recombinant protein in the MSG of transgenic
      silkworms. The recombinant protein secreted in the sericin layer is extractable
      from the cocoon with only a small amount of endogenous silk protein contamination
      by soaking the cocoon in mild aqueous solutions. The possibility of utilizing
      transgenic silkworms as a valuable tool for the mass production of therapeutic
      and industrially relevant recombinant proteins is discussed.

PMID- 21184137
TI  - Establishment of transgenic mice carrying the gene for farnesyl pyrophosphate
      synthase.
AB  - Farnesyl pyrophosphate synthase (FPPS) is an essential enzyme in the mevalonate
      pathway and might be relevant to hypertension and other cardiovascular diseases.
      FPPS transgenic mice were produced by microinjecting a construct with the FPPS
      gene into fertilized eggs derived from an inbred C57BL/6 strain. Three mice were
      identified as carrying copies of the transgene using the PCR. Reverse
      transcription PCR and Western blotting showed that the transgene was expressed in
      heart, liver, lung, ear, brain, thymus, and blood vessels in the transgenic
      mouse. Pathological analysis (hematoxylin and eosin staining) showed that FPPS
      expression did not cause obvious pathological changes in multiple tissues of 6
      week-old transgenic mice. This FPPS transgenic mouse model, may therefore,
      facilitate the investigation of the biological functions of FPPS in vivo.

PMID- 21184138
TI  - Residual dipolar couplings: are multiple independent alignments always possible?
AB  - RDCs for the 14 kDa protein hen egg-white lysozyme (HEWL) have been measured in
      eight different alignment media. The elongated shape and strongly positively
      charged surface of HEWL appear to limit the protein to four main alignment
      orientations. Furthermore, low levels of alignment and the protein's interaction
      with some alignment media increases the experimental error. Together with
      heterogeneity across the alignment media arising from constraints on temperature,
      pH and ionic strength for some alignment media, these data are suitable for
      structure refinement, but not the extraction of dynamic parameters. For an
      analysis of protein dynamics the data must be obtained with very low errors in at
      least three or five independent alignment media (depending on the method used)
      and so far, such data have only been reported for three small 6-8 kDa proteins
      with identical folds: ubiquitin, GB1 and GB3. Our results suggest that HEWL is
      likely to be representative of many other medium to large sized proteins commonly
      studied by solution NMR. Comparisons with over 60 high-resolution crystal
      structures of HEWL reveal that the highest resolution structures are not
      necessarily always the best models for the protein structure in solution.

PMID- 21184139
TI  - Ricoeur's "Petite ethique": an ethical epistemological perspective for clinician
      bioethicists.
AB  - The passage from a posture of clinician to that of clinician-bioethicist poses
      significant challenges for health professionals, most notably with regards to
      theoretical or epistemological views of complex ethical impasses encountered in
      clinical settings. Apprehending these situations from the only clinical
      perspective of the nurse or the doctor, for example, can be very unproductive to
      help solve this kind of situation and certainly poses great limits to the role of
      the clinician-bioethicist. Drawing on my own experience as a former nurse who,
      following graduate studies in bioethics has begun providing ethics consultation
      services, I argue that clinicians must undergo an epistemological transformation
      in order to become clinician-bioethicists. A source of inspiration or framework
      for would-be clinician-bioethicists is, I suggest, the "Petite ethique" developed
      by the contemporary French philosopher Paul Ricoeur. Specifically, clinician
      bioethicists should develop specific core ethical competencies (in line with the
      conclusions of the American Society for Bioethics and Humanities (Core
      competencies for health care ethics consultation, 1998); namely: savoir or
      knowing, savoir faire or knowing how to do, and savoir etre or knowing how to be.

PMID- 21184140
TI  - Effect of cobalt on Escherichia coli metabolism and metalloporphyrin formation.
AB  - Toxicity in Escherichia coli resulting from high concentrations of cobalt has
      been explained by competition of cobalt with iron in various metabolic processes
      including Fe-S cluster assembly, sulfur assimilation, production of free radicals
      and reduction of free thiol pool. Here we present another aspect of increased
      cobalt concentrations in the culture medium resulting in the production of cobalt
      protoporphyrin IX (CoPPIX), which was incorporated into heme proteins including
      membrane-bound cytochromes and an expressed human cystathionine beta-synthase
      (CBS). The presence of CoPPIX in cytochromes inhibited their electron transport
      capacity and resulted in a substantially decreased respiration. Bacterial cells
      adapted to the increased cobalt concentration by inducing a modified mixed acid
      fermentative pathway under aerobiosis. We capitalized on the ability of E. coli
      to insert cobalt into PPIX to carry out an expression of CoPPIX-substituted heme
      proteins. The level of CoPPIX-substitution increased with the number of passages
      of cells in a cobalt-containing medium. This approach is an inexpensive method to
      prepare cobalt-substituted heme proteins compared to in vitro enzyme
      reconstitution or in vivo replacement using metalloporphyrin heme analogs and
      seems to be especially suitable for complex heme proteins with an additional
      coenzyme, such as human CBS.

PMID- 21184141
TI  - A novel metabolic pathway for biodegradation of DDT by the white rot fungi,
      Phlebia lindtneri and Phlebia brevispora.
AB  - 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT) was used as the substrate for
      a degradation experiment with the white rot fungi Phlebia lindtneri GB-1027 and
      Phlebia brevispora TMIC34596, which are capable of degrading polychlorinated
      dibenzo-p-dioxin (PCDD) and polychlorinated biphenyls (PCBs). Pure culture of P.
      lindtneri and P. brevispora with DDT (25 MUmol l(-1)) showed that 70 and 30% of
      DDT, respectively, disappeared in a low-nitrogen medium after a 21-day incubation
      period. The metabolites were analyzed using gas chromatography/mass spectrometry
      (GC/MS). Both fungi metabolized DDT to 1,1-dichloro-2,2-bis(4-chlorophenyl)ethane
      (DDD), 2,2-bis(4-chlorophenyl)acetic acid (DDA) and 4,4-dichlorobenzophenone
      (DBP). Additionally, DDD was converted to DDA and DBP. DDA was converted to DBP
      and 4,4-dichlorobenzhydrol (DBH). While DBP was treated as substrate, DBH and
      three hydroxylated metabolites, including one dihydroxylated DBP and two
      different isomers of monohydroxylated DBH, were produced from fungal cultures,
      and these hydroxylated metabolites were efficiently inhibited by the addition of
      a cytochrome P-450 inhibitor, piperonyl butoxide. These results indicate that the
      white rot fungi P. lindtneri and P. brevispora can degrade DBP/DBH through
      hydroxylation of the aromatic ring. Moreover, the single-ring aromatic
      metabolites, such as 4-chlorobenzaldehyde, 4-chlorobenzyl alcohol and 4
      chlorobenzoic acid, were found as metabolic products of all substrate,
      demonstrating that the cleavage reaction of the aliphatic-aryl carbon bond occurs
      in the biodegradation process of DDT by white rot fungi.

PMID- 21184142
TI  - Country of birth and risk of hospitalization due to heart failure: a Swedish
      population-based cohort study.
AB  - To explore the relation between country of birth and risk of hospitalization due
      to heart failure (HF). All 40-89 year-old inhabitants in the city of Malmo,
      Sweden (n = 114,917, of whom 15.2% were born outside Sweden) were followed from
      November 1st, 1990 until December 31st, 2007. During a mean follow-up of 13.5 +/-
      5.3 years, a total of 7,640 individuals (47.4% men) were discharged from hospital
      with first-ever HF as primary diagnosis. Of them, 1,243 individuals had
      myocardial infarction (MI) before or concurrent with the HF hospitalization. The
      risk of HF was compared between immigrants from selected countries and Swedish
      natives. The overall analysis showed substantial differences among immigrant
      groups (P < 0.001). Compared to Swedish natives, significantly increased HF risk
      was found among immigrants from Finland (HR (hazard ratio): 1.40; 95% CI, 1.10
      1.81), Former Yugoslavia (1.45: 1.23-1.72) and Hungary (1.48: 1.16-1.89), taking
      age, sex, marital status, annual income and housing condition into account.
      Analysis results were similar when cases with MI before or concurrent with the HF
      hospitalization were included in the analysis. In general, the risk of HF was
      significantly higher among immigrants from high-income and middle-income
      countries. Marital status, annual income and housing condition were also
      significant independent risk factors for HF in this population. There are
      substantial differences in risk of hospitalization due to HF among immigrants
      from different countries that can not be explained by socioeconomic factors. To
      what extent these differences could be explained by biological risk factors
      remains to be explored.

PMID- 21184143
TI  - Cystatin C estimated renal dysfunction predicts T wave axis deviation in US
      adults: results from NHANES III.
AB  - Patients with impaired kidney function are at increased risk of ventricular
      arrhythmia and sudden death. The association between chronic kidney disease and
      frontal T wave axis deviation, a cardiovascular risk factor, in individuals
      without heart disease is unexplored and unknown. To test the hypothesis that
      chronic kidney disease predicts frontal T-wave axis deviation, American
      participants 40 years of age or older from NHANES III, were categorized as having
      and not having chronic kidney disease based on glomerular filtration rates
      estimated by both serum cystatin C and serum creatinine and serum creatinine
      alone. Frontal T-wave axis deviation was measured from the standard 12-lead
      electrocardiogram. Multivariable adjustments for age, ace, smoking, metabolic
      syndrome, albuminuria, left ventricular mass, QRS duration and heart rate were
      performed. In multivariable weighted regression analysis, the odds ratio for
      abnormal frontal T wave axis deviations and their corresponding 95% CIs in
      patients with decreased glomerular filtration rate determined by an equation
      included cystatin and creatinine was 1.90 (1.20-3.32). The odds ratio of frontal
      T wave axis deviation due to decreased kidney function, determined using an
      equation included serum creatinine alone, was 1.65 (1.10-2.90). This study
      suggests that abnormal frontal T wave axis deviation abnormalities occur in
      subjects with chronic kidney disease. Those with decline in renal function should
      be considered at risk for potentially serious T-wave associated arrhythmias and
      thus carefully monitored.

PMID- 21184144
TI  - Transcriptional silencing of N-Myc downstream-regulated gene 1 (NDRG1) in
      metastatic colon cancer cell line SW620.
AB  - N-Myc downstream-regulated gene 1 (NDRG1) plays vital roles in tumor metastasis
      suppression and is frequently silenced in metastatic colon cancers. NDRG1 is
      silenced in a highly metastatic colon cancer cell line SW620. The objective of
      this study was to investigate the potential mechanisms involved in silencing of
      the NDRG1 gene. SW480 and SW620 are two colon cancer cell lines established from
      the same patient with different metastatic potentials, making them an ideal model
      for investigation of metastatic mechanisms. Knockdown of NDRG1 in SW480 to a
      level that is similar to that in SW620 also modulated cell cycle and
      proliferation in SW480 towards the status of the highly metastatic SW620.
      Epigenetic mechanisms of the transcriptional control of NDRG1 were investigated.
      The silencing of NDRG1 in SW620 was not due to promoter hyper-methylation as
      bisulfite sequencing of the NDRG1 promoter showed minimal DNA methylation in both
      cell lines. On the other hand, chromatin immunoprecipitation showed a
      significantly higher level of RNA polymerase II (Pol II) association with the
      NDRG1 promoter in SW480 compared to SW620, in agreement with its gene expression
      level. The low Pol II binding at the NDRG1 promoter in SW620 was associated with
      gene-wide decrease in histone H4 acetylation and increase in histone H3 serine 10
      phosphorylation. Meanwhile, the NDRG1 coding region showed much higher histone H3
      lysine 4 methylation in SW480. In conclusion we observed unique histone
      modifications in two colon cancer cell lines with different metastatic
      potentials, indicating possible mechanisms for the down-regulation of NDRG1 in
      metastatic SW620.

PMID- 21184145
TI  - Tetraspanins and tumor progression.
AB  - Transmembrane protein tetraspanins either promote or suppress tumor invasion and
      metastasis. Their effects on tumor progression depend on the multimolecular
      transmembrane complex called tetraspanin-enriched microdomain (TEM) and are
      attributed to the alterations in the (1) motogenic and mitogenic behaviors and/or
      (2) microenvironmental interactions of tumor cells. As the modifiers of cell
      membrane structure and function, tetraspanins have emerged as diagnostic and
      prognostic markers and therapeutic targets for tumor progression.

PMID- 21184147
TI  - Controlled release of anti-inflammatory siRNA from biodegradable polymeric
      microparticles intended for intra-articular delivery to the temporomandibular
      joint.
AB  - PURPOSE: As the next step in the development of an intra-articular controlled
      release system to treat painful temporomandibular joint (TMJ) inflammation, we
      developed several biodegradable poly(DL-lactic-co-glycolic acid) (PLGA)-based
      microparticle (MP) formulations encapsulating a model anti-inflammatory small
      interfering RNA (siRNA) together with branched poly(ethylenimine) (PEI) as a
      transfecting agent. The effect of siRNA loading and N:P ratio on the release
      kinetics of siRNA-PEI polyplexes was determined, and the size and N:P ratio of
      the polyplexes released over time was characterized. METHODS: Polyplex-loaded
      PLGA MPs were prepared using an established double emulsion technique. Increasing
      the pH of the release samples enabled siRNA-PEI dissociation and subsequent
      measurement of the release of each component over 28 days. Polyplex diameter was
      measured for all release samples and compared to freshly prepared siRNA-PEI under
      simulated physiologic conditions. RESULTS: Systematic variation of siRNA loading
      and N:P ratio resulted in distinct siRNA and PEI release profiles. Polyplex
      diameter remained constant despite large variations in the relative amounts of
      siRNA and PEI. Excess PEI was sequestered through complexation with 500-1,000 nm
      diameter PLGA MP-derived particles, including small MPs and PLGA degradation
      products. CONCLUSIONS: These PLGA MP formulations show exciting potential as the
      first intra-articular TMJ controlled release system.

PMID- 21184148
TI  - The effect of human bone marrow stroma-derived heparan sulfate on the ex vivo
      expansion of human cord blood hematopoietic stem cells.
AB  - PURPOSE: In order to address cell dose limitations associated with the use of
      cord blood hematopoietic stem cell (HSC) transplantation, we explored the effect
      of bone marrow stroma-derived heparan sulfate (HS) on the ex vivo expansion of
      HSCs. METHODS: Heparan sulfate was isolated and purified from the conditioned
      media of human bone marrow stromal cells and used for the expansion of cord blood
      derived CD34(+) cells in the presence of a cocktail of cytokines. RESULTS: The
      number of myeloid lineage-committed progenitor cells was increased at low dosage
      of HS as illustrated by an increase in the total number of colony-forming cells
      (CFC) and colonies of erythroid (BFU-E) and granulocyte-macrophage (CFU-GM)
      precursors. Notably, the stroma-derived HS did not alter the growth of CD34(+)
      HSCs or negatively affect the levels of various HSC phenotypic markers after
      expansion. CONCLUSIONS: This study shows that HS secreted into solution by
      stromal cells has the capacity to support hematopoietic cytokines in the
      maintenance and expansion of HSCs. The incorporation of stroma-derived HS as a
      reagent may improve the efficacy of cord blood HSC transplantation by enhancing
      the number of committed cells and accelerating the rate of engraftment.

PMID- 21184149
TI  - New 4-maleamic acid and 4-maleamide peptidyl chalcones as potential multitarget
      drugs for human prostate cancer.
AB  - PURPOSE: The objective of this study was to investigate the effect of new 4
      maleamic acid and 4-maleamide peptidyl chalcone derivatives against human
      prostate cancer in vitro and in vivo. METHODS: From a series of 21 chalcones, the
      effects of the three best inhibitors of PC-3 and LNCaP cell viability on growth,
      including cell cycle changes, adhesion, migration, and cell invasion, as well as
      their ability to inhibit angiogenesis, clonogenic activity, and matrix
      metalloproteinases MMP-2 and MMP-9, were tested. The effects in vivo were studied
      in PC-3 and LNCaP xenografts. RESULTS: Three of the examined chalcones reduced
      cell viability in both cell lines in a strong dose- and time-dependent manner. An
      inhibition of the cell cycle progress was observed. These changes were
      accompanied with the inhibition of cell adhesion, migration, and invasion as well
      as with reduced neovascularization in chick embryos, tumor colony formation, and
      MMP-9 activity. The in vivo results demonstrated the strong activity of these
      structures as inhibitors of tumor development in nude mice compared to non
      treated animals. CONCLUSION: The results suggest the multitarget efficacy of 4
      maleamic acid and 4-maleamide peptidyl chalcones against human prostate cancer
      cells and emphasize the potential therapeutic relevance of these compounds.

PMID- 21184150
TI  - Paclitaxel-loaded poly(n-butylcyanoacrylate) nanoparticle delivery system to
      overcome multidrug resistance in ovarian cancer.
AB  - PURPOSE: The aim of this study was to test the ability of paclitaxel-loaded
      poly(butylcyanoacrylate) (PBCA) nanoparticles to overcome multidrug resistance
      (MDR) in human ovarian resistant cells (A2780/T) and investigate its possible
      mechanism. METHODS: We prepared paclitaxel-loaded PBCA nanoparticles by
      interfacial polymerization method. The physicochemistry of the nanoparticles was
      characterized. The cytotoxicity of paclitaxel-loaded PBCA nanoparticles was
      measured by MTT assay. Calcein-AM assay was used to analyze the P-glycoprotein (P
      gp) function, and the expression of MDR-1 mRNA in A2780/T cells treated with drug
      loaded nanoparticles was defined by QRT-PCR. RESULTS: The nanoparticles were
      approximately spherical in shape with an average diameter of 224.5 +/- 5.7 nm.
      The encapsulation efficiency was 99.23%. The in vitro drug release profile
      exhibited a biphasic pattern. The drug formulated in PBCA nanoparticles showed a
      greater cytotoxicity than paclitaxel against A2780/T cells. Paclitaxel-loaded
      PBCA as well as blank PBCA nanoparticles decreased P-gp function in a dose
      dependent manner, suggesting the efficacy of the drug-loaded nanoparticle system
      on overcoming MDR. There was no significant effect on inhibition to the
      expression of MDR1 mRNA. CONCLUSIONS: Paclitaxel-loaded PBCA nanoparticles can
      enhance cytotoxicity and overcome MDR through a mechanism of the inhibition of P
      gp function caused by the nanoparticles system.

PMID- 21184151
TI  - Binding characterization of recombinant odorant-binding proteins from the
      parasitic wasp, Microplitis mediator (Hymenoptera: Braconidae).
AB  - Chemoreception in insects is mediated by small odorant-binding proteins (OBPs)
      that are believed to carry lipophilic stimuli to the olfactory receptor cells
      through the aqueous sensillar lymph. Binding experiments and recent structural
      studies of OBPs have illustrated their versatility and ability to accommodate
      ligands of different shapes and chemical structures. We expressed and purified
      seven recombinant OBPs (MmedOBP1-MmedOBP7) from the parasitic wasp, Microplitis
      mediator (Hymenoptera: Braconidae) in a prokaryotic expression system. With 4,4'
      dianilino-1,1'-binaphthyl-5,5'-sulfonic acid (bis-ANS) as a fluorescent probe,
      the ligand-binding specificities of these seven MmedOBPs with 50 small organic
      compounds were investigated in vitro. The results revealed that all of the M.
      mediator OBPs can bind a wide variety of odorant molecules with different binding
      affinities. The best ligand for all seven MmedOBPs was beta-ionone. MmedOBP2
      showed affinity for some aromatic compounds, whereas MmedOBP4 and MmedOBP6 bound
      several terpenoids. MmedOBP5 bound beta-ionone, but did not bind any of the other
      potential ligands that we tested.

PMID- 21184152
TI  - The tumor stromal microenvironment as modulator of malignant behavior.

PMID- 21184153
TI  - Intelligent postoperative morbidity prediction of heart disease using artificial
      intelligence techniques.
AB  - Endovascular aneurysm repair (EVAR) is an advanced minimally invasive surgical
      technology that is helpful for reducing patients' recovery time, postoperative
      morbidity and mortality. This study proposes an ensemble model to predict
      postoperative morbidity after EVAR. The ensemble model was developed using a
      training set of consecutive patients who underwent EVAR between 2000 and 2009.
      All data required for prediction modeling, including patient demographics,
      preoperative, co-morbidities, and complication as outcome variables, was
      collected prospectively and entered into a clinical database. A discretization
      approach was used to categorize numerical values into informative feature space.
      Then, the Bayesian network (BN), artificial neural network (ANN), and support
      vector machine (SVM) were adopted as base models, and stacking combined multiple
      models. The research outcomes consisted of an ensemble model to predict
      postoperative morbidity after EVAR, the occurrence of postoperative complications
      prospectively recorded, and the causal effect knowledge by BNs with Markov
      blanket concept.

PMID- 21184154
TI  - Expanding the universe of cytokines and pattern recognition receptors: galectins
      and glycans in innate immunity.
AB  - Effective immunity relies on the recognition of pathogens and tumors by innate
      immune cells through diverse pattern recognition receptors (PRRs) that lead to
      initiation of signaling processes and secretion of pro- and anti-inflammatory
      cytokines. Galectins, a family of endogenous lectins widely expressed in infected
      and neoplastic tissues have emerged as part of the portfolio of soluble mediators
      and pattern recognition receptors responsible for eliciting and controlling
      innate immunity. These highly conserved glycan-binding proteins can control
      immune cell processes through binding to specific glycan structures on pathogens
      and tumors or by acting intracellularly via modulation of selective signaling
      pathways. Recent findings demonstrate that various galectin family members
      influence the fate and physiology of different innate immune cells including
      polymorphonuclear neutrophils, mast cells, macrophages, and dendritic cells.
      Moreover, several pathogens may actually utilize galectins as a mechanism of host
      invasion. In this review, we aim to highlight and integrate recent discoveries
      that have led to our current understanding of the role of galectins in host
      pathogen interactions and innate immunity. Challenges for the future will embrace
      the rational manipulation of galectin-glycan interactions to instruct and shape
      innate immunity during microbial infections, inflammation, and cancer.

PMID- 21184155
TI  - Molecular diagnosis of severe combined immunodeficiency--identification of IL2RG,
      JAK3, IL7R, DCLRE1C, RAG1, and RAG2 mutations in a cohort of Chinese and
      Southeast Asian children.
AB  - Severe combined immunodeficiencies (SCID) are a group of rare inherited disorders
      with profound defects in T cell and B cell immunity. From 2005 to 2010, our unit
      performed testing for IL2RG, JAK3, IL7R, RAG1, RAG2, DCLRE1C, LIG4, AK2, and
      ZAP70 mutations in 42 Chinese and Southeast Asian infants with SCID adopting a
      candidate gene approach, based on patient's gender, immune phenotype, and
      inheritance pattern. Mutations were identified in 26 patients, including IL2RG (n
      = 19), IL7R (n = 2), JAK3 (n = 2), RAG1 (n = 1), RAG2 (n = 1), and DCLRE1C (n =
      1). Among 12 patients who underwent hematopoietic stem cell transplantation,
      eight patients survived. Complications and morbidities during transplant period
      were significant, especially disseminated bacillus Calmette-Guerin disease which
      was often difficult to control. This is the first cohort study on SCID in the
      Chinese and Southeast Asian population, based on a multi-centered collaborative
      research network. The foremost issue is service provision for early detection,
      diagnosis, management, and definitive treatment for patients with SCID. National
      management guidelines for SCID should be established, and research into an
      efficient platform for genetic diagnosis is needed.

PMID- 21184157
TI  - Determinants of the use of prenatal care in rural China: the role of care
      content.
AB  - Several maternal demographic factors have been identified to influence the timing
      of starting prenatal care and its adequate use. However, how the content of
      prenatal care modifies these factors has not been studied previously. Using a
      representative sample collected for other purposes in rural China, we examined
      the factors predicting the uptake of prenatal care by taking into account the
      content of care (advice: on nutrition during pregnancy, diseases and pregnancy
      related problems, and on child care after birth; and routine tests: blood
      pressure, blood tests, and ultrasound). We studied 1,479 women who answered a
      house-hold KAP (knowledge, attitude, and practice) survey (97% response rate)
      collected after a prenatal care intervention from 2001 to 2003 in 20 townships
      located in a county in Anhui Province. A multinomial logistic regression was used
      for the analysis. The most prominent factors that predicted late start of
      prenatal care and inadequate care were younger age, low maternal income, and
      having more than one child. When we adjusted for the content of care, the
      influence of these factors on the use of prenatal care attenuated to varying
      degrees: in some cases there was up to 20% reduction in the values of the risk
      estimates, while in other cases the statistical significance of the estimates
      were lost. It is important to take into account the content of prenatal care when
      assessing the factors predicting women's use of prenatal care.

PMID- 21184159
TI  - Sight word instruction for students with autism: an evaluation of the evidence
      base.
AB  - This paper reviews the evidence on sight word instruction as a method of teaching
      students with autism and significant cognitive and verbal limitations to read
      printed words. Nine single-subject studies were rated using Reichow et al.'s (J
      Autism Dev Disord 38:1311-1319, 2008) evaluative method for identifying evidence
      based practice, and studies with at least adequate methodology were analyzed to
      identify common intervention features. Results yielded evidence in support of a
      massed trials approach featuring student response to a succession of items,
      differential positive reinforcement, systematic prompting, and use of visual
      supports. Across studies, students learned to identify printed words, even those
      with limited oral language and no prior reading instruction. However, no studies
      addressed the effects of sight word instruction on broad literacy outcomes.

PMID- 21184160
TI  - Brief report: teaching situation-based emotions to children with autistic
      spectrum disorder.
AB  - Many individuals with autism spectrum disorders (ASD) have difficulty recognizing
      emotions in themselves and others. Three children (all males) participated in the
      study. In a multi-element design children with ASD were trained to tact situation
      based emotions (i.e., "happy", "sad", "angry", and "afraid") using novel video
      based scenarios. To increase the likelihood that each child would learn a
      generalized repertoire of emotion understanding, multiple exemplars of emotion
      identification were trained using a multi-component procedure. The results
      indicated significant increases in tacting situation-based emotions. To evaluate
      the generalization of training, novel video stories were employed that depicted
      the trained emotions. The findings indicated generalization of situation-based
      emotional tacting to the novel video stories.

PMID- 21184158
TI  - Changes in the mother-child relationship during the transition to adulthood for
      youth with autism spectrum disorders.
AB  - We examined whether exiting high school was associated with changes in the mother
      child relationship. Participants were 170 mothers of youth with ASD who were part
      of our larger longitudinal study and who exited high school during the study;
      data were collected four times over 7 years. Results indicated improvement in the
      mother-child relationship while in high school; however, improvement in all
      indices slowed or stopped after exit. Mothers of youth with ASD without an
      intellectual disability (ID) and who had more unmet service needs evidenced the
      least improvement after exit. Our findings provide further evidence that the
      years after high school exit are a time of increased risk, especially for those
      with ASD without ID and whose families are under-resourced.

PMID- 21184161
TI  - Brief report: autistic-like traits in childhood predict later age at menarche in
      girls.
AB  - We investigated the relationship between autistic-like traits in early childhood
      and age at menarche in typically developing girls. Autistic-like symptoms were
      measured at age 2 years using the Child Behaviour Checklist, and age at menarche
      (AAM) was determined prospectively using self-report questionnaires at age 8, 10,
      14 and 17 years. Girls with 'high' autistic-like symptoms at age 2 years
      demonstrated significantly later AAM (n = 70; M = 13.07 years; SD = 1 year) than
      girls reported to show 'typical' (n = 216; M = 12.72 years; SD = 1.1) or 'low' (n
      = 47; M = 12.66 years; SD = 1.13 years) levels of these behaviors. These data
      further establish a link between the autism phenotype and later AAM and may
      provide insights into the etiology of the condition.

PMID- 21184163
TI  - Does cognitive impairment explain behavioral and social problems of children with
      neurofibromatosis type 1?
AB  - Thirty NF1-patients (mean age 11.7 years, SD = 3.3) and 30 healthy controls (mean
      age 12.5 years, SD = 3.1) were assessed on social skills, autistic traits,
      hyperactivity-inattention, emotional problems, conduct problems, and peer
      problems. Cognitive control, information processing speed, and social information
      processing were measured using 5 computer tasks. GLM analyses of variance showed
      significant group differences, to the disadvantage of NF1-patients, on all
      measures of behavior, social functioning and cognition. General cognitive ability
      (a composite score of processing speed, social information processing, and
      cognitive control) accounted for group differences in emotional problems, whereas
      social information processing accounted for group differences in conduct
      problems. Although reductions were observed for group differences in other
      aspects of behavior and social functioning after control for (specific) cognitive
      abilities, group differences remained evident. Training of cognitive abilities
      may help reducing certain social and behavioral problems of children with NF1,
      but further refinement regarding associations between specific aspects of
      cognition and specific social and behavioral outcomes is required.

PMID- 21184162
TI  - Sex-specific heterosis in line crosses of mice selectively bred for high
      locomotor activity.
AB  - When populations with similar histories of directional selection are crossed,
      their offspring may differ in mean phenotype as compared with the average for the
      parental populations, often exhibiting enhancement of the mean phenotype (termed
      heterosis or hybrid vigor). We tested for heterosis in a cross of two replicate
      lines of mice selectively bred for high voluntary wheel running for 53
      generations. Mice were paired to produce four sets of F1 offspring: two purebred
      High Runner (HR) lines and the hybrid reciprocal crosses. The purebred HR showed
      statistically significant, sex-dependent differences in body mass, wheel
      revolutions, running duration, mean running speed, and (controlling for body
      mass) organ masses (heart ventricles, liver, spleen, triceps surae muscle).
      Hybrid males ran significantly more revolutions than the purebred males, mainly
      via increased running speeds, but hybrid females ran intermediate distances,
      durations, and speeds, as compared with the purebred females. In both sexes,
      ventricles were relatively smaller in hybrids as compared with purebred HR.
      Overall, our results demonstrate differential and sex-specific responses to
      selection in the two HR lines tested, implying divergent genetic architectures
      underlying high voluntary exercise.

PMID- 21184164
TI  - Effect of domestication on aggression in gray Norway rats.
AB  - A comparative analysis of intermale aggression in the resident-intruder test was
      conducted with gray rats from a wild unselected population bred at the laboratory
      for three generations and gray rats selected for elimination (tame) and
      enhancement (aggressive) of aggressiveness towards human for 71-72 generations.
      Males from the laboratory line Wistar were used as neutral opponents. Rats from
      the tame line were characterized by reduced aggression manifest as longer attack
      latency, decreased number of attacks, upright postures, chases, kicks, and
      shorter total time of aggressive behavior compared to unselected males. There was
      no significant difference in the attack latency and the total time of aggression
      between rats of the aggressive line and unselected rats. A trend to decrease in
      the number of attacks, chases and upright postures and to increase in
      contribution of lateral threat postures to the total time of aggression was
      observed for males of the aggressive line. Plasma corticosterone in unselected
      males not presented with intruders and after their presentation was higher than
      in males of both selected lines. Comparative behavioral analysis of agonistic
      behaviors in rats from the aggressive and tame lines to opponents of different
      lines (Wistar, tame, aggressive) showed that the presence of an intruder from the
      aggressive line can enhance aggressive responses in residents from the tame line.
      Thus, selection for domestication of gray rats caused a significant attenuation
      of aggressive behavior without affecting the basic agonistic repertoire.

PMID- 21184165
TI  - Genetical genomic analysis of complex phenotypes using the PhenoGen website.
AB  - Our laboratory has developed an online interactive resource called PhenoGen (
      http://phenogen.ucdenver.edu ) which provides an archive of brain and other organ
      gene expression data from a panel of 20 common inbred mouse strains, and three
      recombinant inbred (RI) panels (two mouse and one rat). DNA microarray data can
      also be uploaded to the site where numerous analytical tools can be implemented.
      An important advantage to the archived data is that each array represents data
      from a single animal and each strain was sampled 4-7 times, providing an estimate
      of genetic variance (heritability) of individual transcript levels. These panels
      also allow genetic mapping of expression QTLs. Overlap of eQTLs with phenotypic
      QTLs provides a powerful approach to candidate gene identification. These methods
      are briefly described here and we encourage the use of our site for both
      scientific discovery and as a teaching tool in quantitative genetics.

PMID- 21184167
TI  - Selective breeding for increased home cage physical activity in collaborative
      cross and Hsd:ICR mice.
AB  - Selective breeding experiments for increased wheel running and open field
      behavior have identified genetic and neurobiological factors associated with
      increased voluntary physical activity in mice, but no previous study has directly
      selected for increased distance traveled in the home cage. Therefore, within
      family selection was applied to increase home cage activity as measured by
      continuous video tracking using two different starting populations, G2:F1
      Collaborative Cross (CC) and Hsd:ICR mice. Genetic correlations with distance
      traveled on running wheels and in the open field were evaluated by mid-parent
      offspring regression. A significant response to selection was observed in CC but
      not Hsd:ICR. Wheel running was heritable in both populations but not
      significantly genetically correlated with home cage activity. Open field was not
      heritable in either population. We conclude that different genes and neural
      circuits influence physical activity in the home cage as compared to wheel
      running or open field. Selective breeding for home cage activity in CC mice
      warrants further exploration.

PMID- 21184166
TI  - No association of the YWHAE gene with schizophrenia, major depressive disorder or
      bipolar disorder in the Han Chinese population.
AB  - YWHAE is a gene encoding 14-3-3epsilon, which is highly conserved across species,
      from bacteria to humans, and binds to phosphoserine/phosphothreonine motifs in a
      sequence-specific manner. YWHAE has been reported to be associated with
      schizophrenia in a study based on the Japanese population. Here, we conducted a
      genetic association analysis between common SNPs in the YWHAE gene and
      psychiatric diseases including schizophrenia, major depressive disorder and
      bipolar disorder in Han Chinese samples (1140 schizophrenia cases, 1140 major
      depressive disorder cases, 1140 bipolar disorder cases and 1140 normal controls).
      We studied 11 SNPs, seven of which had previously been reported as significant,
      in YWHAE. No association was found with schizophrenia, major depressive disorder
      or bipolar disorder. Considering the size of our sample sets (power > 90%), our
      results suggest that the YWHAE does not play a major role in schizophrenia, major
      depressive disorder or bipolar disorder in the Han Chinese population.

PMID- 21184168
TI  - Fine mapping quantitative trait loci that influence alcohol preference behavior
      in the High and Low Alcohol Preferring (HAP and LAP) mice.
AB  - The High Alcohol Preferring (HAP1) and Low Alcohol Preferring (LAP1) mouse lines
      were selectively bred for differences in alcohol intake. The HAP1 and LAP1 mice
      are essentially non-inbred lines that originated from an outbred colony of HS/Ibg
      mice, a heterogeneous stock developed from intercrossing 8 inbred strains of
      mice. In a former genomewide SNP association study, we identified quantitative
      trait loci (QTL) on chromosomes 1, 3, 5, and 9 (Bice et al. 2009). Provisional
      QTL were also identified on chromosomes 8 and X. In the present study, using the
      same F2 DNA samples, we placed a much denser set of SNPs within each of those QTL
      regions. Using the same analytical approach employed previously, which utilizes
      ancestral recombination to fine map the QLT interval, we obtained significant LOD
      scores on chromosomes 1, 3, and 9, only. Our results using a dense set of SNP
      markers suggest that there are multiple loci contributing to alcohol preference
      on those three chromosomes.

PMID- 21184169
TI  - Emerging adulthood and leaving foster care: settings associated with mental
      health.
AB  - The present study examined the role of contextual support on mental health during
      the transition to adulthood within a vulnerable group, adolescents leaving foster
      care because of their age. Participants were 265 19- to 23-year-olds who
      retrospectively reported on 3 main contexts of emerging adulthood: housing
      security, educational achievement, and employment attainment in the first 2 years
      after leaving foster care. Mental health measured self-reported emotional
      distress, substance abuse, and deviancy at the time of interview. Growth Mixture
      Modeling empirically identified 3 latent trajectory classes. Stable-Engaged (41%)
      experienced secure housing and increasing connections to education and employment
      over time. Stable-Disengaged (30%) maintained housing but reported decreasing
      rates of education and small increases in employment. Instable-Disengaged (29%)
      experienced chronic housing instability, declined connection to education, and
      failed to attain employment. Stable-Engaged and Stable-Disengaged classes
      reported better mental health compared to the Instable-Disengaged class,
      indicating the importance of housing in transitioning to adulthood.

PMID- 21184170
TI  - Changing meanings through art: a systematization of a psychosocial intervention
      with Chilean women in urban poverty situation.
AB  - This study explores the experiences that women in urban poverty situation have
      about their participation in a psychosocial group intervention mediated by
      artistic techniques. An investigation was done using a qualitative methodology.
      Participants were ten women older than 21 years old who live in Santiago de Chile
      in poverty situation. Two group evaluations were performed during the
      intervention process and once it was completed, ten individual semi-structure
      interviews. The information was analyzed following the proposals of Grounded
      Theory, identifying negative experience about tiredness and sacrifice related to
      the circumstances they live in. It was possible, at the same time, to describe
      the benefits of an artistic activity including a psychosocial work over the
      individual well-being. The artistic creation was revealed as a way of expression,
      of re-viewing oneself and the environment, and relaxation. Transformation is
      discussed concerning self-affirmation, reparation and transference of this
      experience in their lives, as a preventive and protective resource to overcome
      their problems.

PMID- 21184171
TI  - The impact of neighborhood factors on the well-being of survivors of intimate
      partner violence over time.
AB  - Intimate partner violence (IPV) is a pervasive social problem impacting the
      psychological well-being of millions of US women annually. The extant literature
      draws our attention to the devastating mental health effects of IPV, but largely
      overlooks how ecological factors may further explain survivors' well-being. This
      study examined how neighborhood disadvantage may contribute to survivors'
      compromised well-being, in addition to the abuse women experienced. Neighborhood
      disorder and fear of victimization significantly impacted survivors' well-being,
      over and above abuse. Although between-women effects of neighborhood disorder and
      fear were unrelated to change in women's depression or quality of life (QOL),
      significant within-woman effects were detected. Change in neighborhood disorder
      was negatively associated with change in QOL, and this relationship was fully
      mediated by fear. While no direct relationship between change in neighborhood
      disorder and depression was detected, an indirect effect through survivors' fear
      was revealed. Implications for future research and practice are discussed.

PMID- 21184172
TI  - Chasing our tails: psychological, institutional and societal paradoxes in natural
      resource management, sustainability, and climate change in Australia.
AB  - Natural Resource Management (NRM) and Ecologically Sustainable Development (ESD)
      have been guiding frameworks in Australia for a number of decades. Recently, NRM
      and ESD have become central to climate change mitigation. In this paper, we
      explore the psychological paradoxes that function within climate change settings,
      with particular attention devoted to the way that research and development
      reinforces these paradoxes by advocating for participatory forms of inquiry.
      Paradox emerges in NRM at psychological, institutional, and organisational
      levels. Paradoxes are also features of different forms of democracy such as
      neoliberal and participatory democracy. Although NRM, ESD and climate change are
      often conceptualised as distinct issue domains, these policy areas are
      fundamentally interconnected in both theory and in practice. This interconnection
      between these policy and research settings, reflections on paradox, and the
      experience of incorporating community psychology into the paradoxical settings of
      NRM and climate change are captured in this paper.

PMID- 21184173
TI  - Bone marrow cells participate in tumor vessel formation that supports the growth
      of Ewing's sarcoma in the lung.
AB  - An MHC-mismatch bone marrow (BM) transplant Ewing's sarcoma mouse model was used
      to investigate whether BM cells participate in the vessel formation that support
      Ewing's sarcoma lung metastasis. BM cells from H-2K(b/d) donor mice were
      transplanted into sublethally irradiated H-2K(d) recipient mice. Donor BM cells
      were identified using the H-2K(b) marker. Engraftment was confirmed by
      identifying the H-2K(b) IL-1beta-type specific polymorphism. After engraftment
      highly lung metastatic TC71-PM4 cells were injected intravenously. Mice were
      sacrificed 10 weeks after tumor cell injection. Hematoxylin-and-eosin staining
      was performed to identify lung metastatic foci. These tumors were then evaluated
      using immunohistochemical analysis. H-2K(b)-positive cells were found in lung
      metastases but not in normal lung, liver or spleen tissues. Injection of CM-Dil
      labeled BM cells into tumor bearing and control mice showed that nonspecific
      organ migration occurred at 24 h, but that these cells were absent 1 week later
      in control mice. These data suggest that the migration of the H-2K(b) BM cells to
      lung nodules was specific because these cells were observed 14 weeks after
      transplantation. Co-localization of H-2K(b) and CD31 or VE-Cadherin demonstrated
      that some endothelial cells were BM-derived. Co-localization of H-2K(b) and
      Desmin, smooth muscle actin (alpha-SMA) or PDGFR-beta indicated that a fraction
      of pericytes was also BM-derived. These results suggest that BM cells participate
      in the vascular formation that supports the growth of Ewing's sarcoma lung
      metastases. BM cells migrated to the metastatic tumor and differentiated into
      endothelial cells and pericytes. These data indicated that targeting this process
      may have therapeutic potential.

PMID- 21184175
TI  - Liver lipids of female Carcharias taurus (spotted raggedtooth) sharks: a
      comparison between seasons.
AB  - Female raggedtooth sharks (Carcharias taurus) migrate from the waters off the
      eastern Cape past KwaZulu-Natal and up to southern Mozambique and then back on an
      annual basis. They mate off the KwaZulu-Natal coast, gestate the pups off
      Mozambique, then deliver same off the eastern Cape. Prior to mating, they
      hypertrophise their livers and store large amounts of lipid, then towards the end
      of gestation subsist on this stored lipid as well as using it to feed their pups
      in utero. Raggedtooth sharks are aplacental, and hepatic lipids provide nutrients
      to the pups via continued ovulation throughout pregnancy. The fact of the liver
      hypertrophy was well documented, but whether the nature of the stored lipid or
      the amount of lipid per Kg of liver changed with season was unknown. Samples from
      raggedtooth females caught throughout the year were analysed for their lipid and
      fatty acid contents and significant differences noted between lipid, but not
      fatty acid, concentration with certain seasons. Liver mass decreased from spring
      to winter (16.3-9.9 kg) as did lipid concentration (572-326 mg/g). Within the
      fatty acids, 22:6n3 was +/-17%, 20:5n3 +/-7%, total n3 +/-30% and total n6 +/-7%.
      Also, both total polyunsaturates (+/-36%) and total monounsaturates (+/-33%) were
      greater than the total saturates (+/-28%).

PMID- 21184174
TI  - Lead positioning strategies to enhance response to cardiac resynchronization
      therapy.
AB  - Left ventricular lead position is one of the main determinants of CRT response.
      There are several approaches in LV lead positioning that include favoring an
      optimal anatomical position or targeting either the segment with maximal
      mechanical dyssynchrony or a region with maximal electrical delay. The
      conventional LV lead implantation faces several technical difficulties that may
      prevent the obtaining of a stable position and good performance of the LV lead
      without phrenic nerve stimulation. In addition, implant of the LV pacing lead in
      areas with myocardial scar may result in less than optimal cardiac
      resynchronization. Several strategies have been proposed to overcome all these
      obstacles including multimodality cardiac imaging to help in preprocedural or
      intraprocedural identification of the latest activated areas of the LV and the
      potential anatomical constraints. In selected patients, the surgical implant may
      be a solution to overcome these constraints. In the future, LV endocardial or
      epicardial multisite pacing may deliver an enhanced response to CRT.

PMID- 21184176
TI  - Survival of White Ibises (Eudocimus albus) in response to chronic experimental
      methylmercury exposure.
AB  - Although methylated mercury (MeHg) is known to have neurological, immunological,
      reproductive, and endocrine effects on vertebrates at low environmental exposure
      levels, effects on survival of exposed birds have not been demonstrated in the
      wild. Here, we report on survival of the same group of White Ibises (Eudocimus
      albus) during exposure to 4 levels of dietary MeHg in captivity and later as
      depurated free-ranging animals. Ibises were chronically exposed in captivity to
      dietary MeHg in groups at 0 (control), 0.05 (Low), 0.1 (Medium) and 0.3 (High)
      ppm MeHg ww for 43 months. No differences in annualized survival among captive
      MeHg groups were seen within age classes. Survival of all ages taken together was
      significantly lower for Control birds than for Low or Medium dosed birds, but was
      not different from High dosed birds. While this might be evidence of a hormetic
      effect, none of the captive results support the prediction that MeHg impairs
      survival. Using a mark-recapture analysis we found no effects of dose group or of
      Hg exposure on survival or resight probabilities during the first 99 days post
      release to the wild. The latter results suggest that there is no lasting, post
      depuration effect of even high MeHg exposure (0.3 ppm ww dietary) on survival.
      While these results agree with a variety of studies of survival of free-ranging
      birds, we suggest many survival studies have been confounded by seasonal
      depuration through molt, and variation in exposure rates. We suggest future
      studies concentrate on evaluating survival effects during nonmolting periods in
      species for which methylmercury exposure is relatively constant.

PMID- 21184177
TI  - Biogerontological research in Europe: special issue.

PMID- 21184178
TI  - The bronchodilator response of in vivo specific airway compliance in adults with
      asthma.
AB  - A new technique has been developed to determine in vivo airway compliance in
      humans that is specific to airway size and transpulmonary pressure, and can be
      represented as a three-dimensional surface. As yet, the ability of this technique
      to detect changes in specific airway compliance with disease status has not been
      demonstrated. The aim of this study was to assess whether this technique could
      determine changes in airway compliance which are thought to occur with altered
      smooth muscle tone in adults with asthma. Airway compliance was measured and
      displayed as a surface in adults with asthma before and after a reduction in
      smooth muscle tone by bronchodilator administration. Compliance, with respect to
      airway size, was calculated at three specific lung volumes; functional residual
      capacity (FRC), total lung capacity (TLC), and midway between FRC and TLC (MID).
      After bronchodilator, airway compliance increased at FRC and MID in the smaller
      airways (<3 mm). Furthermore, airway compliance under both conditions was greater
      in the smaller airways compared to the larger airways. In conclusion, our method
      may have future utility in assessing changes in airway compliance in respiratory
      diseases such as asthma.

PMID- 21184179
TI  - GDF9 as a candidate gene for prolificacy of Small Tail Han sheep.
AB  - Growth differentiation factor 9 (GDF9) which controls the fecundity of Belclare,
      Cambridge, Santa Ines, Moghani, Ghezel and Thoka ewes was studied as a candidate
      gene for the prolificacy of Small Tail Han sheep. According to the sequence of
      ovine GDF9 gene, six pairs of primers were designed to detect single nucleotide
      polymorphisms of two exons of GDF9 gene in both high fecundity breed (Small Tail
      Han sheep) and low fecundity breed (Dorset sheep) by polymerase chain reaction
      single strand conformation polymorphism (PCR-SSCP). Only the products amplified
      by primers 2-1 and 2-2 displayed polymorphisms. For primer 2-1, three genotypes
      (AA, AB and BB) were detected in both sheep breeds. Sequencing revealed one
      silent mutation (G477A) in exon 2 of GDF9 gene in the BB genotype in comparison
      with the AA, which was known as G3 mutation of GDF9 gene in Belclare and
      Cambridge ewes. The relationship of least squares means for litter size was AA >
      AB > BB in Small Tail Han sheep (P > 0.05). For primer 2-2, two genotypes (CC and
      CD) were detected in both sheep breeds. Sequencing revealed one novel single
      nucleotide mutation (G729T) in exon 2 of GDF9 gene in the CD genotype in
      comparison with the CC, which resulted in an amino acid change (Gln243His). The
      ewes with mutation heterozygous genotype CD had 0.77 (P < 0.01) lambs more than
      those with wild type CC in Small Tail Han sheep. These results preliminarily
      indicated that allele D of GDF9 gene was a potential genetic marker for improving
      litter size in Small Tail Han sheep.

PMID- 21184180
TI  - Molecular cloning and tissue expression of the fatty acid-binding protein (Es
      FABP9) gene in the reproduction seasons of Chinese mitten crab, Eriocheir
      sinensis.
AB  - Fatty acid-binding proteins (FABPs), small cytosolic proteins that function in
      the uptake and utilization of fatty acids, have been extensively studied in
      higher vertebrates while invertebrates have received little attention despite
      similar nutritional requirements during periods of reproductive activity.
      Therefore, a cDNA encoding Eriocheir sinensis FABP (Es-FABP9) was cloned based
      upon EST analysis of a testis cDNA library. The full length cDNA was 898 bp and
      encoded a 136 aa polypeptide that was highly homologous to related genes reported
      in shrimp. Gene expression analysis, as determined by RT-PCR, revealed the
      presence of Es-FABP9 transcripts was widely distributed with high and detectable
      expression levels observed in intestine, ovary, testis and heart, while
      expression were comparable among hepatopancreas, hemolymphe, gills, muscle,
      stomach and brain. Real-time quantitative RT-PCR analysis revealed that Es-FABP9
      expression in testis, hemolymphe, hepatopancreas and ovarian was dependent on the
      status of testis development. Evidence provided in the present report supports a
      role of Es-FABP9 in lipid transport during the period of rapid testis growth in
      E. sinensis, and indirectly confirms the participation of the hepatopancreas,
      testis, hemolymphe and ovarian in lipid nutrient absorption and utilization
      processes.

PMID- 21184181
TI  - Age-related expression profile of the SLC27A1 gene in chicken tissues.
AB  - The solute carrier family 27 (SLC27, also known as fatty acid transport proteins
      [FATPs]) plays important biological roles in cells. However, there is no report
      about the expression profile of SLC27 member in chicken. In this study, we
      quantified the expression of SLC27A1 (FATP1) mRNA in a mountainous black-boned
      chicken breed (MB) and a commercial meat type chicken breed (S01), to discern the
      tissue and age-related specific expression pattern and their potential
      involvement in fat deposition and muscle fatty acid metabolism. Real-time
      quantitative PCR assays were developed for accurate measurement of SLC27A1 mRNA
      levels in different tissues from chicken with different ages (0-12 weeks).
      Expression of SLC27A1 mRNA was detected in all tissues examined. There was a
      significantly age-related change of the SLC27A1 mRNAs in heart, breast muscle
      (BMW), leg muscle (LMW), liver, and abdominal fat (AF) tissues (P < 0.05). The
      breast muscle and leg muscle tissues had the highest expression of SLC27A1 mRNA
      than the other tissues from the same individual at 0, 2 and 4 weeks. The overall
      SLC27A1 mRNA level exhibited a "rise-decline" developmental change in all tissues
      except for breast muscle, subcutaneous fat, and brain. The S01 chicken had a
      higher expression of the SLC27A1 mRNA in breast muscle, subcutaneous fat, and
      heart tissues than the MB chicken. Our results showed that the expression of
      SLC27A1 mRNA in chicken tissues exhibits specific developmental changes and age
      related patterns.

PMID- 21184182
TI  - Effect of genetic variation of CEBPA gene on body measurement and carcass traits
      of Qinchuan cattle.
AB  - In our study, genetic variation in coding region of cattle CCAAT enhancer binding
      protein alpha(namely CEBPA)gene was detected by PCR-RFLP and DNA sequencing
      methods in 215 individuals from Qinchuan cattle breed. Two haplotypes (A and B)
      and three observed genotypes (AA, AB, and BB) were detected. The result of DNA
      sequence showed one mutation by comparisons with NC_007316. The mutation at nt963
      (T>G) were located in coding region of the CEBPA gene. Associations between the
      CEBPA gene genetic variation and the carcass traits were revealed in Qinchuan
      cattle. Least squares analysis revealed a significant statistical effect of the
      CEBPA gene different genotypes on slaughter weight and carcass weight in Qinchuan
      cattle. Individuals with BB genotype showed higher slaughter weight and carcass
      weight than individuals with AA and AB genotypes. Therefore, these results
      suggest that the CEBPA gene is a strong candidate gene that affects carcass
      traits in Qinchuan cattle.

PMID- 21184183
TI  - A model for allocating CDC's HIV prevention resources in the United States.
AB  - The Division of HIV/AIDS Prevention (DHAP) at the Centers for Disease Control and
      Prevention has an annual budget of approximately $325 million for funding HIV
      prevention programs in the U.S. The purpose of this paper is to thoroughly
      describe the methods used to develop a national HIV resource allocation model
      intended to inform DHAP on allocation strategies that might improve the overall
      effectiveness of HIV prevention efforts. The HIV prevention resource allocation
      problem consists of choosing how to apportion prevention resources among
      interventions and populations so that HIV incidence is minimized, given a budget
      constraint. We developed an epidemic model that projects HIV infections over time
      given a specific allocation scenario. The epidemic model is then embedded in a
      nonlinear mathematical optimization program to determine the allocation scenario
      that minimizes HIV incidence over a 5-year horizon. In our model, we consider the
      general U.S. population and specific at-risk populations. The at-risk populations
      include 15 subgroups structured by gender, race/ethnicity and HIV transmission
      risk group. HIV transmission risk groups include high-risk heterosexuals, men who
      have sex with men and injection drug users. We consider HIV screening
      interventions and interventions to reduce HIV-related risk behaviors. The output
      of the model is the optimal funding scenario indicating the amounts to be
      allocated to all combinations of populations and interventions. For illustrative
      purposes only, we provide a sample application of the model. In this example, the
      optimal allocation scenario is compared to the current baseline funding scenario
      to highlight how the current allocation of funds could be improved. In the
      baseline allocation, 29% of the annual budget is aimed at the general population,
      while the model recommends targeting 100% of the budget to the at-risk
      populations with no allocation targeted to the general population. Within the
      allocation to behavioral interventions the model recommends an increase in
      targeting diagnosed positives. Also, the model allocation suggests a greater
      focus on MSM and IDUs with a 72% of the annual budget allocated to them, while
      the baseline allocation for MSM and IDUs totals 37%. Incorporating future
      epidemic trends in the decision-making process informs the selection of
      populations and interventions that should be targeted. Improving the use of funds
      by targeting the interventions and population subgroups at greatest risk may lead
      to improved HIV outcomes. These models can also direct research by pointing to
      areas where the development of cost-effective interventions can have the most
      impact on the epidemic.

PMID- 21184184
TI  - PedsQLTM Cognitive Functioning Scale in pediatric liver transplant recipients:
      feasibility, reliability, and validity.
AB  - OBJECTIVE: The PedsQLTM (Pediatric Quality of Life InventoryTM) is a modular
      instrument designed to measure health-related quality of life and disease
      specific symptoms. The PedsQLTM Cognitive Functioning Scale was developed as a
      brief generic symptom-specific instrument to measure cognitive functioning. The
      objective of the present study was to determine the feasibility, reliability, and
      validity of the PedsQLTM Cognitive Functioning Scale in pediatric liver
      transplant recipients. METHODS: The 6-item PedsQLTM Cognitive Functioning Scale
      and the PedsQLTM 4.0 Generic Core Scales were completed by pediatric liver
      transplant recipients ages 8-18 years (n = 215) and parents of pediatric liver
      transplant recipients ages 2-18 years (n = 502). Both patient self-report and
      parent proxy-report were available for 212 cases. The 72-item Behavior Rating
      Inventory of Executive Function (BRIEF), a widely validated measure of executive
      functioning, was completed by 100 parents and 56 teachers on a subset of
      patients. RESULTS: The PedsQLTM Cognitive Functioning Scale demonstrated minimal
      missing responses (0.0%, child report, 0.67%, parent report), achieved excellent
      reliability (alpha = 0.88 child report, 0.94 parent report), distinguished
      between pediatric patients with liver transplants and healthy children supporting
      discriminant validity, and was significantly correlated with the PedsQLTM 4.0
      Generic Core Scales and the BRIEF supporting construct and concurrent validity,
      respectively. Pediatric liver transplants recipients experienced cognitive
      functioning comparable to long-term pediatric cancer survivors. CONCLUSIONS: The
      results demonstrate the feasibility, reliability, discriminant, construct, and
      concurrent validity of the PedsQLTM Cognitive Functioning Scale in pediatric
      liver transplant recipients.

PMID- 21184185
TI  - Validation of the AQLQ12+ among adolescents and adults with persistent asthma.
AB  - BACKGROUND: To date, there is limited psychometric evidence on the Asthma Quality
      of Life Questionnaire (AQLQ12 +) among populations that include adolescents and
      adults. OBJECTIVE: To provide evidence of the psychometric properties of the
      AQLQ12+ as a measure of asthma-specific quality of life (QOL) in patients with
      persistent asthma treated with a combination of inhaled glucocorticoid and long
      acting beta2-agonist, as well as explore the predictors of at least a minimally
      important AQLQ12+ improvement. METHODS: The psychometric properties of the
      AQLQ12+ were assessed through post hoc analysis of two large (n = 740 and 778)
      Phase III, randomized, double-blinded, placebo-controlled efficacy studies of
      mometasone furoate/formoterol fumarate (MF/F) combination compared with
      monotherapy in subjects with persistent asthma previously treated with either low
      dose or medium-dose inhaled glucocorticoids. RESULTS: With 15% and 8%
      participation from 12- to 17-year olds, blinded trial data demonstrated excellent
      reproducibility (ICC range: 0.76-0.85) and moderate-to-strong construct validity
      with other measures of asthma health at baseline and over time for the AQLQ12 +.
      A greater percentage of the MF/F treatment group (44%) achieved an important
      change at 26 weeks on the AQLQ12+ compared with formoterol fumarate (F, 23%) and
      placebo (18%) treatment groups in the low-dose study (P < 0.001) and the medium
      dose study (50% (MF/F) versus 34% (F) and 23% (placebo); P < 0.001). Pre
      randomization nighttime awakenings and rescue medications use were significant
      predictors of AQLQ12+ improvement. CONCLUSIONS: These findings provide strong
      support for the measurement properties of the AQLQ12+ among patients with
      persistent asthma and confidence in the AQLQ12+ improvements demonstrated by the
      MF/F treatment group.

PMID- 21184186
TI  - Measuring health-related quality of life in Kashin-Beck disease using EQ-5D.
AB  - PURPOSE: To assess health-related quality of life in patients with Kashin-Beck
      disease (KBD) in China. METHODS: A total of 684 participants from endemic areas
      of the Shaanxi province in China were recruited through a multistage stratified
      random sampling. Amongst those, 368 participants were diagnosed with KBD while
      the rest of 316 were non-KBD participants. Differences between KBD and non-KBD
      groups were analysed for the percentage of reporting any problems in each of EQ
      5D five dimensions, EQ-5D index scores and visual analogue scale (VAS) scores.
      RESULTS: KBD patients have a higher percentage of reporting any problems in each
      of EQ-5D dimension than non-KBD participants and a general population in Beijing.
      The most affected dimension is pain/discomfort, followed by mobility,
      anxiety/depression, and usual activities, and self-care being the last. The mean
      EQ-5D index and VAS scores for KBD patients are significantly lower than those of
      non-KBD participants. CONCLUSION: This study is the first attempt to measure the
      health-related quality of life in KBD patients. The results of the study show
      that KBD has a severe impact on patients' health-related quality of life as
      measured by EQ-5D. It particularly causes great problems in the dimensions of
      pain/discomfort, mobility and anxiety/depression.

PMID- 21184187
TI  - 4D parathyroid CT as the initial localization study for patients with de novo
      primary hyperparathyroidism.
AB  - BACKGROUND: Preoperative localization of parathyroid tumors of primary
      hyperparathyroidism (pHPT) is required for minimally invasive parathyroidectomy
      (MIP). Parathyroid four-dimensional computed tomography (4DCT) has mainly been
      used as an adjunct to other imaging modalities in the remedial setting. 4DCT was
      evaluated as the initial localization study in de novo patients with pHPT.
      MATERIALS AND METHODS: A total of 87 consecutive patients underwent
      parathyroidectomy for pHPT from August 2008 to November 2009. 4DCT was introduced
      as the preferred imaging modality instead of sestamibi with SPECT (SeS) in April
      2009. Results of the imaging studies [4DCT, SeS, and ultrasonography (US)],
      operative and, pathologic findings, and biochemical measurements were evaluated.
      RESULTS: In this study, 84% of patients (73 of 87) underwent an US, 59.8% (52 of
      87) a SeS, and 38.0% (33 of 87) had a 4DCT. 4DCT had improved sensitivity (85.7%)
      over SeS (40.4%) and US (48.0%) to localize parathyroid tumors to the correct
      quadrant of the neck (P < 0.005) as well as to localize (lateralize) the
      parathyroid lesions to one side of the neck (93.9% for 4DCT vs. 71.2% for US and
      61.5% for SeS; P < 0.005). 4DCT correctly predicted multiglandular disease (MGD)
      in 85.7% (6 of 7) patients, whereas US and SeS were unable to detect MGD in any
      case. All patients achieved cure based on intraoperative parathyroid hormone
      (PTH) measurements and normalization of intact PTH and S-Ca during follow-up.
      CONCLUSIONS: 4DCT provides significantly greater sensitivity than SeS and US for
      precise localization of parathyroid tumors of pHPT. Additionally, it correctly
      predicted MGD in a majority of patients.

PMID- 21184188
TI  - Tissue hOGG1 genotype predicts bladder cancer prognosis: a novel approach using a
      peptide nucleic acid clamping method.
AB  - BACKGROUND: Tissue genotyping is a more useful approach than using blood genomic
      DNA, because the tumor tissues can reflect the effects of somatic mutations in
      cancer. We investigated the value of the human oxoguanine glycosylase (hOGG1)
      genotype determined in tumor tissues as a prognostic indicator for bladder cancer
      (BC) using a novel technological approach. METHODS: A total of 335 DNA samples
      from patients with primary BC were analyzed by peptide nucleic acid (PNA)
      mediated real-time polymerase chain reaction (PCR) clamping to characterize the
      association between genetic polymorphisms within hOGG1 codon 326 and the
      clinicopathological characteristics of primary BC patients. RESULTS: Tumor stage
      and number were significantly associated with the hOGG1 codon 326 genotype in
      nonmuscle invasive bladder cancer (NMIBC) patients. Compared with Cys326Ser and
      Ser326Ser, the Cys326Cys genotype had a greater progression-free survival benefit
      in patients with muscle invasive bladder cancer (MIBC). Univariate and
      multivariate Cox regression analyses indicated that the hOGG1 Cys326Cys genotype
      has a protective effect against progression in MIBC (hazard ratio, 0.360 and
      0.314, respectively). CONCLUSIONS: The hOGG1 tissue genotype is associated with
      aggressive clinicopathological features in NMIBC and with progression in patients
      with MIBC. Results suggest that the hOGG1 tissue genotype represents a promising
      marker for assessing BC prognosis in the clinical setting.

PMID- 21184189
TI  - Preanalytical interferences compromise the clinical validity of matrix
      metalloproteinase 1 as marker of colorectal cancer.

PMID- 21184190
TI  - Initial experience with videoscopic inguinal lymphadenectomy.
AB  - BACKGROUND: Inguinofemoral lymphadenectomy is associated with frequent and marked
      incision-related morbidity. Our initial feasibility study of videoscopic inguinal
      lymphadenectomy (VIL) for melanoma showed appropriate nodal yield and anatomic
      dissection. Although a limited suprafascial dissection has been reported in the
      urologic literature, we report our growing experience with VIL applying a
      comprehensive approach to dissection. METHODS: Patients with inguinal metastases
      from varied malignancies were offered VIL. With institutional review board
      approval, procedures were performed via three ports: one at the apex of the
      femoral triangle, a second medial to the adductor, and a third lateral to
      sartorius. Femoral vessels were skeletonized, and all lymphatic tissue within the
      femoral triangle to 5 cm up onto the external oblique aponeurosis was resected.
      Specimens were removed through the apical port via a specimen bag.
      Clinicopathologic and perioperative outcome data were recorded. RESULTS: Forty
      five VILs were performed in 32 patients: 19 had unilateral VILs, and 13 had
      bilateral VILs for neuroendocrine, extramammary Paget disease, or varied
      genitourinary malignancies. Nine procedures (20%) were performed in women. Median
      age was 61 (range 16-87) years. Median body mass index was 30 (range 19-53).
      Median operative time was 165 (range 75-245) minutes, median length of stay was 1
      (range 1-14) day, and median drain duration was 15 days. Median number of
      collected nodes was 11 (range 4-24), and the largest node removed was 5.6 cm in
      size. Wound complications were observed in 8 cases (18%). Six patients (13%)
      developed cellulitis without any wound dehiscences, 1 patient developed a seroma,
      and 1 patient with diabetes had mild skin flap necrosis, which resolved with
      minimal local care. CONCLUSIONS: VIL is an alternative approach to traditional
      open inguinal lymphadenectomy. In our growing experience, node retrieval is
      appropriate and wound complications are substantially fewer than reported via an
      open approach. Further comparative analysis of VIL and traditional inguinofemoral
      lymphadenectomy is being pursued in a randomized, prospective trial.

PMID- 21184191
TI  - Resveratrol induces Notch2-mediated apoptosis and suppression of neuroendocrine
      markers in medullary thyroid cancer.
AB  - BACKGROUND: Currently, complete surgical resection is the only curative option
      for medullary thyroid cancer (MTC). Previous work has shown the Notch pathway is
      a potent tumor suppressor in MTC and that resveratrol activates the Notch pathway
      in carcinoid cancer, a related neuroedocrine malignancy. In this study, we
      hypothesized that the effects observed on carcinoid cells could be extended to
      MTC. METHODS: MTC cells treated with varying doses of resveratrol were assayed
      for viability by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium
      bromide) assay. Western blot analysis for achaete-scute complex-like 1 (ASCL1),
      chromogranin A (CgA), full-length and cleaved caspase 3, and poly-ADP ribose
      polymerase (PARP) was performed. Quantitative real-time polymerase chain reaction
      (qPCR) was used to measure relative mRNA expression. RESULTS: Treatment with
      resveratrol resulted in growth suppression and an increase in the cleavage of
      caspase-3 and PARP. A dose-dependent inhibition of ASCL1, a neuroedocrine
      transcription factor, was observed at the protein and mRNA levels. Protein levels
      of CgA, a marker of hormone secretion, were also reduced after treatment with
      resveratrol. A dose-dependent induction of Notch2 mRNA was observed by qPCR.
      CONCLUSIONS: Resveratrol suppresses in vitro growth, likely through apoptosis, as
      demonstrated by cleavage of caspase-3 and PARP. Furthermore, resveratrol
      decreased neuroedocrine markers ASCL1 and chromogranin A. Induction of Notch2
      mRNA suggests that this pathway may be central in the anti-MTC effects observed.

PMID- 21184192
TI  - Comparison of endoscopic and robotic thyroidectomy.
AB  - BACKGROUND: Endoscopic thyroidectomy is a technically challenging procedure.
      Robot-assisted thyroidectomy has been recently introduced and offers improved
      visualization and dexterity. The present study compared conventional endoscopic
      and robotic thyroidectomy for thyroid cancer patients in terms of perioperative
      outcomes and learning curve. All operations were performed by the same surgeon.
      MATERIALS AND METHODS: Between April 2007 and March 2010, 96 patients underwent
      endoscopic thyroidectomy (endoscopy group) and 163 patients underwent robotic
      thyroidectomy (robot group). A gasless transaxillary approach was used in both
      groups. The 2 groups were compared in terms of patient characteristics,
      perioperative clinical results, complications, and pathologic details. Learning
      curves for the 2 procedures were compared based on the number of cases required
      to reach a consistent operation time. RESULTS: Patient characteristics were
      similar for both groups. The mean total operation time for thyroidectomy with
      central compartment neck dissection was 142.7 +/- 52.1 min in the endoscopy group
      and 110.1 +/- 50.7 min in the robot group (P = .041). Both patient groups were
      similar in terms of pathological features including TNM stage, intraoperative
      blood loss, length of hospital stay, and complication rate. However, the mean
      number of retrieved central lymph nodes was 2.4 +/- 1.9 for the endoscopy group
      and 4.5 +/- 1.5 for the robot group (P = .004). The learning curve was 55-60
      cases for endoscopic thyroidectomy and 35-40 cases for robotic thyroidectomy.
      CONCLUSION: Robotic thyroidectomy was found to be superior to endoscopic
      thyroidectomy in terms of operation time, lymph node retrieval, and learning
      curve. Complication rates and postoperative hospital stay were similar for the 2
      procedures.

PMID- 21184193
TI  - Factors associated with postoperative pulmonary morbidity after esophagectomy for
      cancer.
AB  - BACKGROUND: Most studies analyzing risk factors for pulmonary morbidity date from
      the early 1990s. Changes in technology and treatment such as minimally invasive
      esophagectomy (MIE) and neoadjuvant treatment mandate analysis of more
      contemporary cohorts. METHODS: Predictive factors for overall and specific
      pulmonary morbidity in 858 patients undergoing esophagectomy between 1998 and
      2008 in five Australian university hospitals were analyzed by logistic regression
      models. RESULTS: A total of 394 patients underwent open esophagectomy, and 464
      patients underwent MIE. A total of 259 patients received neoadjuvant
      chemoradiotherapy, 139 preoperative chemotherapy alone, and 2 preoperative
      radiotherapy alone. In-hospital mortality was 3.5%. Smoking and the number of
      comorbidities were risk factors for overall pulmonary morbidity (odds ratio [OR]
      1.47, P = 0.016; OR 1.35, P = 0.001) and pneumonia (OR 2.29, P = 0.002; 1.56, P =
      0.005). The risk of respiratory failure was higher in patients with more
      comorbidities (OR 1.4, P = 0.035). Respiratory comorbidities (OR 3.81, P = 0.017)
      were strongly predictive of postoperative acute respiratory distress syndrome
      (ARDS). ARDS (4.51, P = 0.032) or respiratory failure (OR 8.7, P < 0.001), but
      not anastomotic leak (OR 2.22, P = 0.074), were independent risk factors for
      death. MIE (OR 0.11, P < 0.001) and thoracic epidural analgesia (OR 0.12, P =
      0.003) decreased the risk of respiratory failure. Neoadjuvant treatment was not
      associated with an increased risk of pulmonary complications. CONCLUSIONS:
      Preoperative comorbidity and smoking were risk factors for respiratory
      complications, whereas neoadjuvant treatment was not. MIE and the use of thoracic
      epidural analgesia decreased the risk of respiratory failure. Respiratory failure
      and ARDS were the only independent factors associated with an increased risk of
      in-hospital death, whereas anastomotic leakage was not.

PMID- 21184196
TI  - Engineering and ethical constraints.

PMID- 21184195
TI  - Inhibition of chemiluminescence and chemotactic activity of phagocytes in vitro
      by the extracts of selected medicinal plants.
AB  - The methanol extracts of 20 selected medicinal plants were investigated for their
      effects on the respiratory burst of human whole blood, isolated human
      polymorphonuclear leukocytes (PMNs) and isolated mice macrophages using a
      luminol/lucigenin-based chemiluminescence assay. We also tested the effect of the
      extracts on chemotactic migration of PMNs using the Boyden chamber technique. The
      extracts of Curcuma domestica L., Phyllanthus amarus Schum & Thonn and C.
      xanthorrhiza Roxb. were the samples producing the strongest oxidative burst of
      PMNs with luminol-based chemiluminescence, with IC(50) values ranging from 0.5 to
      0.7 MUg/ml. For macrophage cells, the extracts which showed strong suppressive
      activity for luminol-based chemiluminescence were C. xanthorrhiza and Garcinia
      mangostana L. Among the extracts studied, C. mangga Valton & Vazsjip, Piper
      nigrum L. and Labisia pumila var. alata showed strong inhibitory activity on
      lucigenin-amplified oxidative burst of PMNs, with IC(50) values ranging from 0.9
      to 1.5 MUg/ml. The extracts of Zingiber officinale Rosc., Alpinia galangal (L.)
      Willd and Averrhoa bilimbi Linn showed strong inhibition on the chemotaxic
      migration of cells, with IC(50) values comparable to that of ibuprofen (1.5
      MUg/ml). The results suggest that some of these plants were able to modulate the
      innate immune response of phagocytes at different steps, emphasizing their
      potential as a source of new immunomodulatory agents.

PMID- 21184197
TI  - APOE epsilon 4 allele and CSF APOE on cognition in HIV-infected subjects.
AB  - The significance of the cerebrospinal fluid (CSF) Apolipoprotein E (APOE) level
      and whether it might have differential effects on brain function due to the
      presence of APOE epsilon 4 allele(s) in HIV-infected patients are unknown.
      However, APOE epsilon 4 allele has been associated with greater incidence of HIV
      associated dementia and accelerated progression of HIV infection. Here, we show
      further evidence for the role of APOE epsilon 4 in promoting cognitive
      impairment. We measured the APOE levels in the CSF of HIV-infected individuals.
      HIV+ subjects showed lower CSF APOE proteins than SN controls (-19%, p= 0.03).
      While SN subjects with or without epsilon 4 allele showed no difference in CSF
      APOE levels, epsilon 4+ HIV+ subjects had similar levels to the SN subjects but
      higher levels than epsilon 4- HIV+ subjects (+34%, p= 0.01). Furthermore, while
      HIV+ subjects with epsilon 2 or epsilon 3 allele(s) showed a positive
      relationship between their CSF APOE levels and cognitive performance on the speed
      of processing domain (r= +0.35, p= 0.05), epsilon 4+ HIV+ subjects, in contrast,
      exhibited a negative relationship such that those with higher levels of CSF
      APOE(4) performed worse on the HIV Dementia Scale (r= -0.61, p= 0.02), had lower
      Global Cognitive Scores (r= -0.57, p= 0.03), and had poorer performance on tests
      involving learning (epsilon 4 allele x [APOE] interaction, p = 0.01). Our
      findings also suggest that the relatively higher levels of CSF APOE in epsilon 4+
      HIV+ (having primarily APOE4 isoforms) may negatively impact the brain and lead
      to poorer cognitive outcomes, while those individuals without the epsilon 4
      allele (with primarily APOE2 or APOE3 isoforms) may show compensatory responses
      that lead to better cognitive performance.

PMID- 21184199
TI  - Phenotypic and cytologic studies of lymphoid cells and monocytes in primary
      culture of porcine bone marrow during infection of African swine fever virus.
AB  - We have modeled in vitro infection of African swine fever virus (ASFV) in primary
      unstimulated cells of the porcine bone marrow and have studied the phenotypical
      changes in the population of porcine lymphoid cells by cytophotometry. Monocytes
      and large-sized lymphocytes completely vanished in 72 h of infection which is
      result of high sensitivity of those cells to ASFV. We describe DNA synthesis in
      monocytes at 24 h post infection. Cytophotometry of the uninfected cells revealed
      the few number of atypical lymphocytes and lymphoblasts after 72 h of
      cultivation; whereas in viral infected cultures, atypical cells appeared in large
      quantity (about 14%) with 24 h. Most of atypical lymphocytes and lymphoblasts had
      altered nucleus, and only a small number of atypical cells had additional
      nucleus. The cytophotometry of main and additional nuclei showed that DNA content
      didn't exceed diploid standard which indicates that the additional nuclei were
      consequence of fragmentation of nuclei in lymphocytes.

PMID- 21184198
TI  - Arachidonic acid induces production of 17,20beta-dihydroxy-4-pregnen-3-one (DHP)
      via a putative PGE2 receptor in fish follicles from the Eurasian perch.
AB  - The effects of docosahexaenoic, eicosaenoic and arachidonic acids (DHA, EPA and
      ARA, respectively) on sex-steroid and prostaglandin (PG) production were
      investigated in Eurasian perch (Perca fluviatilis) follicles using an in- vitro
      incubation technique. Only ARA was able to induce the production of 17,20beta
      dihydroxy-4-pregnen-3-one (DHP), the hormone produced by vitellogenic follicles
      undergoing final meiotic maturation, as well as the production of PGE2 and
      PGF2alpha by the follicles. This work also investigated, using a preliminary
      pharmacological approach, the presence of a functional PGE2-like receptor in fish
      follicles. Exogenous PGE2 and butaprost (specific agonist of the EP2 receptor)
      stimulated DHP production. A second experiment assayed the cyclic adenosine
      monophosphate (cAMP) production by the follicles after 24 h of incubation with
      the agonist and antagonist of the EP2 receptor. As observed in mammals, we
      concluded that the cAMP produced in response to PGE2 was probably mediated by an
      intracellular mechanism via a PGE2-like receptor. This is the first
      pharmacological indication of this type of receptors in fish follicles. This
      study also indicates that ARA, and its derivatives, PGE2 and PGF2alpha, may act
      on final follicle maturation in Eurasian perch.

PMID- 21184200
TI  - Comparison of electroporation and ChariotTM for delivery of beta-galactosidase
      into mammalian cells: strategies to use trehalose in cell preservation.
AB  - There are many compounds that can and have been used as cryoprotectants including
      disaccharides such as trehalose. Many organisms in nature use trehalose to help
      protect themselves at colder temperatures. Trehalose has also been used to a
      limited extent for the preservation of mammalian cells and tissues, but mainly as
      a supplement to other cryoprotectants like dimethyl sulfoxide. Recently, the use
      of trehalose as the primary cryoprotectant has gained much interest because of
      its low-potential cytotoxicity. Trehalose does not readily pass through mammalian
      cells membranes and research has shown that it is most effective when present on
      both sides of the cell membrane prior to preservation. Different strategies for
      introducing disaccharide sugars into cells have been investigated with limited
      success. In this study, two separate strategies are investigated for the
      introduction of disaccharide sugars into cells. Electroporation using an electric
      pulse to create temporary holes in the membrane so that molecules could pass
      through and a transport peptide (ChariotTM) that covalently binds to the molecule
      of interest and then moves it across the membrane. Both strategies have the
      potential to load disaccharide sugars into cells at concentrations that would
      provide ample protection during preservation. In preparation for cryopreservation
      studies, smooth muscle cells that are difficult to cryopreserve using
      conventional preservation protocols were used to evaluate and compare the
      translocation potential of these two strategies using beta-galactosidase.
      Assessment of each loading strategy was done by measuring viability and the
      presence of beta-galactosidase inside the cells. The results indicate that both
      methods appear feasible as potential delivery systems and that treatment
      cytotoxicity can be minimized. The next step is definition of the best loading
      strategy to introduce trehalose into cells followed by preservation by freezing.

PMID- 21184201
TI  - The reporting of gastric band slip and related complications; a review of the
      literature.
AB  - Laparoscopic adjustable gastric banding is a safe and effective treatment for
      morbid obesity. Long-term complications include band slippage, gastric pouch
      dilatation and gastric erosion. Rates of band slippage reported in the literature
      range from less than 1% to over 20%. The aim of this review was to explore
      whether differences in the reporting of this complication contributed to the
      variability in this outcome measure. A full literature search was undertaken
      using EMBASE and MEDLINE search engines. Forty studies were selected for analysis
      based on inclusion and exclusion criteria. Each was scrutinised for outcome
      reporting methods and related fields. Accurate definitions for relevant terms
      were derived from the best available evidence. Considerable variations in device
      deployed, operative approach, band fixation technique, and outcome reporting
      mechanisms were seen between the studies. The explanation and definition of terms
      used within manuscripts were also seen to vary between studies. A consensus needs
      to be reached on how best to report complications such as gastric band slippage.
      We suggest which information should be included by authors to allow for accurate
      and reproducible reporting of such outcomes in the future.

PMID- 21184202
TI  - Selection of reference genes for qRT-PCR in high fat diet-induced hepatic
      steatosis mice model.
AB  - With the epidemic proportions of obesity worldwide and the concurrent prevalence
      of hepatic steatosis, there is an urgent need for better understanding the
      intrinsic mechanism of hepatic steatosis, especially the changes of gene
      expression underlying the development of hepatic steatosis and its associated
      abnormal liver function. Quantitative real-time PCR (qRT-PCR) is a sensitive and
      highly reproducible technique of gene expression analysis. However, for accurate
      and reliable gene expression results, it is vital to have an internal control
      gene expressed at constant levels under all the experimental conditions being
      analyzed for. In this study, the authors validated candidate reference genes
      suitable for qRT-PCR profiling experiments using livers from control mice and
      high fat diet-induced obese mice. Cross-validation of expression stability of ten
      selected reference genes using three popular algorithms, GeNorm, NormFinder, and
      BestKeeper found HPRT1 and GAPDH as most stable reference genes. Thus, HPRT1 and
      GAPDH are recommended as stable reference genes most suitable for gene expression
      studies in the development of hepatic steatosis.

PMID- 21184203
TI  - Point-of-care testing.
AB  - The availability of rapid, point-of-care (POC) tests has significantly expanded
      the capacity of both developed and resource-constrained countries (RCCs) to
      diagnose HIV, with immunochromatographic tests most commonly used in these
      settings. This has been especially important in programs for prevention of mother
      to-child transmission, in both RCCs and the developed world. However, suitable
      POC tests are not yet commercially available for diagnosis of neonatal HIV, where
      persistence of maternal antibody in the infant precludes the use of current
      antibody tests during the first 12 to 18 months. In addition, measurement of CD4+
      T cells, CD4%, and HIV viral load still relies on sophisticated laboratory
      infrastructure, constraining the delivery of appropriate care to many HIV
      infected patients. Continued effort is required in the development and validation
      of additional POC tests to support HIV patient care, and in quality assurance in
      manufacturing and in test performance in the field to ensure appropriate use of
      existing and new POC tests.

PMID- 21184204
TI  - Percutaneous mitral repair: patient selection, results, and future directions.
AB  - Percutaneous heart valve therapies are rapidly changing our approach to valvular
      heart diseases. Currently, mitral valve surgery is the treatment of choice for
      patients suffering from severe symptomatic mitral regurgitation. However surgery,
      because of its inherent risks, is not applicable to all patients, particularly
      for the elderly with comorbidities. Catheter-based mitral repair systems offer a
      new option to those high-risk patients. The edge-to-edge repair using the
      MitraClip device (Evalve, Menlo Park, CA), simulating the surgical Alfieri stitch
      via percutaneous approach proved to be a safe and feasible technique. This
      article discusses the currently available data for the MitraClip transcatheter
      mitral repair system.

PMID- 21184205
TI  - The biodegradation of zein in vitro and in vivo and its application in implants.
AB  - A unique polymer-based sustained-release implant drug delivery system was
      prepared by using biocompatible and biodegradable Zein as the skeleton material.
      After preparing Zein colloids, the Zein-loaded implant rods were formulated by
      injection molding followed by evaporating the solvent, and being coated with
      poly(lactic-co-glycolic) acid (PLGA) solution. Drug release kinetics was examined
      by using Fluorouracil (5-FU) as model drug. Nearly zero-order release was
      achieved for the model drugs for a period of 0-25 days when the implants were
      incubated in distilled water at 37  degrees C. And then the degradation kinetics
      of the rods in vivo and in vitro were evaluated, which indicated that Zein could
      be absorbed by body and has good degradation property. The effects of different
      ratios of Zein/5-FU and the rods' diameter on drug release were studied,
      respectively. The plasma concentration of 5-FU in the implants were determined by
      HPLC after implanting a single dose of the implants in rats. All data were
      subsequently processed by using the computer program 3P97, and the values were
      showed as follows: the area under the plasma concentration-time curve (AUC) value
      was 321.88 (MUg/ml) * day, and the mean residence time (MRT) value was 23.05
      days. The sustained-release implants of Zein/5-FU were successfully formulated.
      The uniqueness of the article is that Zein has been used as a skeleton material
      in implant delivery system for the first time and zero-order release kinetics has
      been obtained successfully.

PMID- 21184207
TI  - Synergistic effect of coronary artery disease risk factors on long-term survival
      in patients with normal exercise SPECT studies.
AB  - BACKGROUND: Normal exercise single-photon emission computed tomography (SPECT)
      studies are associated with a low event rate (<1.0%/year) during short-term
      follow-up. The influence of cardiac risk factors on long-term outcomes in such
      patients has not been well studied. MATERIAL AND METHODS: 2,597 patients (55 +/-
      12 years, male 41%) without a history of heart disease and a normal exercise
      SPECT between the years 1995 and 2006 were followed for a mean 6.8 +/- 3.1 years
      for all-cause mortality assessed for using the Social Security Death Index.
      Baseline clinical risk factors and other clinical information were recorded for
      each patient and compared to outcomes. RESULTS: The mortality rate was 0.9%/year
      for our overall study population but varied according to individual baseline risk
      factors. Three coronary artery disease (CAD) risk factors were significant
      predictors of all-cause mortality: hypertension, diabetes, and smoking. When all
      three were absent, long-term all-cause mortality rate averaged 0.2%/year and when
      all three were present, all-cause mortality averaged 1.8%/year, constituting a
      5.7-fold adjusted increase in risk (95% CI 2.7-12.8, P < .0001). CONCLUSIONS:
      During follow-up, annualized mortality rate varies markedly according to the
      number of CAD risk factors in patients without known heart disease and a normal
      exercise SPECT stress. Despite overall excellent long-term prognosis of a normal
      exercise SPECT, the burden of traditional CAD risk factors exert a strong
      synergistic influence on long-term survival and warrant aggressive treatment in
      this patient population.

PMID- 21184206
TI  - Breakout session: Ethnic and gender differences in diabetic foot management and
      amputations.
AB  - BACKGROUND: Although the health status of all Americans has improved
      substantially in the past century, gender and ethnic disparities still persist.
      Gender and ethnic disparities in diabetic foot management and amputations are an
      important but largely ignored issue in musculoskeletal health care.
      QUESTIONS/PURPOSES: Our purposes were to (1) clarify where we are now, (2)
      describe ways to get where we need to go, and (3) suggest solutions for how we
      get there, with respect to gender and ethnic disparities in diabetic foot
      management and amputations. WHERE ARE WE NOW?: Studies investigating
      socioeconomic, cultural, racial, and biologic contributing factors on gender and
      ethnic musculoskeletal healthcare disparities have found no single root cause.
      Studies into disparities in diabetic foot management and amputation have
      discordant methodologies and most are retrospective. Effective intervention
      strategies to eliminate these disparities are nonexistent. WHERE DO WE NEED TO
      GO?: The orthopaedic leadership should lead the movement to create a clearly
      defined strategy and assist young investigators to gain access to large datasets
      to study this problem. Orthopaedic specialty society leaders should help to
      create valid outcome tools, especially on peripheral vascular disease and
      amputations. HOW DO WE GET THERE?: The working group proposed a three-pronged
      strategy of education, research, and advocacy to help address this problem.

PMID- 21184208
TI  - Partial volume correction incorporating Rb-82 positron range for quantitative
      myocardial perfusion PET based on systolic-diastolic activity ratios and phantom
      measurements.
AB  - BACKGROUND: Quantitative myocardial PET perfusion imaging requires partial volume
      corrections. METHODS: Patients underwent ECG-gated, rest-dipyridamole, myocardial
      perfusion PET using Rb-82 decay corrected in Bq/cc for diastolic, systolic, and
      combined whole cycle ungated images. Diastolic partial volume correction relative
      to systole was determined from the systolic/diastolic activity ratio, systolic
      partial volume correction from phantom dimensions comparable to systolic LV wall
      thicknesses and whole heart cycle partial volume correction for ungated images
      from fractional systolic-diastolic duration for systolic and diastolic partial
      volume corrections. RESULTS: For 264 PET perfusion images from 159 patients (105
      rest-stress image pairs, 54 individual rest or stress images), average resting
      diastolic partial volume correction relative to systole was 1.14 +/- 0.04,
      independent of heart rate and within +/-1.8% of stress images (1.16 +/- 0.04).
      Diastolic partial volume corrections combined with those for phantom dimensions
      comparable to systolic LV wall thickness gave an average whole heart cycle
      partial volume correction for ungated images of 1.23 for Rb-82 compared to 1.14
      if positron range were negligible as for F-18. CONCLUSION: Quantitative
      myocardial PET perfusion imaging requires partial volume correction, herein
      demonstrated clinically from systolic/diastolic absolute activity ratios combined
      with phantom data accounting for Rb-82 positron range.

PMID- 21184209
TI  - Comparison of the atherosclerotic burden among asymptomatic patients vs matched
      volunteers.
AB  - BACKGROUND: While asymptomatic patients should have a lower risk of cardiac
      events compared to symptomatic patients referred for cardiac stress testing,
      comparable event rates have been noted in some prior prognostic studies. To test
      if a high burden of undetected atherosclerosis among asymptomatic patients helps
      explain such findings, we compared atherosclerotic burden, as measured by
      coronary artery calcium (CAC) scanning, in propensity-matched groups of
      volunteers and asymptomatic patients. METHODS: CAC scans were performed on a
      research basis in 136 asymptomatic patients referred for exercise myocardial
      perfusion SPECT and in 1,398 volunteers. We performed matching by propensity
      scores to compare volunteers with the same CAD risk factor profile as our
      asymptomatic patients. RESULTS: Among our matched groups, asymptomatic patients
      had significantly greater mean CAC scores than volunteers (394 +/- 805 vs 151 +/-
      349, P = .001), primarily due to a higher frequency of CAC scores >1,000 (15.4%
      vs 2.5%, P < .001). Inducible myocardial ischemia by SPECT was present in 7% of
      patients, but was selectively concentrated among those with CAC scores >1,000,
      occurring in 27.0% of such patients vs only 1.9% among patients with CAC scores
      <1,000 (P < .0001). CONCLUSIONS: In contrast to asymptomatic volunteers,
      asymptomatic patients referred for cardiac stress testing possess more extensive
      atherosclerosis as measured by CAC. Among asymptomatic patients with high CAC
      scores, the frequency of concomitant inducible myocardial ischemia is high. These
      results help explain prior prognostic studies concerning asymptomatic patients
      and indicate the importance of making a clinical distinction between healthy
      subjects and asymptomatic patients with respect to atherosclerotic risk.

PMID- 21184212
TI  - An automatic method of the isocentre position verification for micromultileaf
      collimator based radiosurgery system.
AB  - An efficient procedure has been developed using an electronic portal imaging
      device (EPID) and in-house written software for verification of a target
      simulator alignment with the radiation isocentre. A 5 mm tungsten ball is aligned
      to a linac isocentre based on a lasers intersection point. The BrainLab((r)) m3TM
      add-on multileaf collimator (MLC) forms a rectangular open field of 1.8 * 1.8
      cm(2). At five different gantry and couch positions, EPID images are acquired. A
      computer search algorithm determines the centres of both a radiation field and a
      tungsten ball for each image. Based on the geometric differences between those
      centres, the optimum three-dimensional shift of a tungsten ball is calculated in
      order to minimise the misalignment error between a target simulator and a
      radiation isocentre. A decision can then be made whether or not the tungsten ball
      and lasers intersection point should be corrected. The accuracy and precision of
      the procedure has been tested and found to be 0.04 and 0.24 mm respectively at
      95% confidence interval. The procedure is also quicker, easier and more reliable
      to perform compared to the previous method based on irradiating a radiographic
      film.

PMID- 21184210
TI  - Health behaviours as mediating pathways between socioeconomic position and body
      mass index.
AB  - BACKGROUND: Low socioeconomic position is widely reported to associate with high
      body mass index (BMI). We, however, lack scientific evidence if health behaviours
      mediate the association between socioeconomic position and BMI. PURPOSE: The aims
      of the study were to explore associations of education and income with BMI and to
      study the mediating pathways through health behaviours. METHOD: Study population
      comprised 3,995 Finnish men and women aged 25 to 64 years who participated in a
      cross-sectional, population-based FINRISK 2002 Study. Participants' height and
      weight were measured to calculate BMI. Self-administered questionnaire assessed
      education, household income, leisure time physical activity, sitting behaviour,
      dietary habits, smoking, and alcohol consumption. Structural equation modelling
      with latent variables was applied to estimate age-adjusted direct and indirect
      associations between variables. RESULTS: Most health behaviours mediated the
      association between socioeconomic position and BMI. Strongest and most consistent
      mediators were diet and sitting in men and women, as well as leisure time
      physical activity in women. Health behaviours clustered strongly with each other.
      CONCLUSIONS: The strongest indirect associations between socioeconomic position
      and BMI were mediated through variables related to energy balance, i.e. diet and
      sedentariness. To reduce the socioeconomic variation in overweight and obesity,
      the main focus should be on food and sedentary behaviours while also taking into
      account the gender differences and clustering of unhealthy behaviours.

PMID- 21184211
TI  - Testicular oxidative damage and role of combined antioxidant supplementation in
      experimental diabetic rats.
AB  - The present study was designated to assess oxidative damage and its effect on
      germ cell apoptosis in testes of streptozotocin (STZ)-induced diabetic rats. The
      role of antioxidant supplementation with a mixture of vitamins E and C and alpha
      lipoic acid for protection against such damage was also evaluated. Forty-five
      adult male rats were randomly divided into three groups: group I, control, non
      diabetic rats; group II, STZ-induced, untreated diabetic rats; group III, STZ
      induced diabetic rats supplemented with a mixture of vitamins E and C and alpha
      lipoic acid. Glycated hemoglobin (HbA(1C)), glucose, and insulin levels were
      estimated in blood samples. Malondialdehyde (MDA), the activities of the enzymes
      superoxide dismutase (SOD), glutathione peroxidase (GPx), and caspase-3 in
      addition to testosterone (T) level were all determined in testicular tissues.
      Histopathological studies using H&E stain, as well as, immunohistochemical
      detection of apoptosis using (TUNEL) method were also performed. Blood glucose
      and HbA(1c) were significantly increased while insulin was significantly
      decreased in STZ-induced diabetic rats as compared with controls. In rat
      testicular tissues, MDA, and caspase-3 activity were significantly elevated while
      SOD and GPx enzymatic activities as well as T level were significantly decreased
      in diabetic rats as compared with control group. Antioxidant supplementation to
      diabetic rats restored the testicular enzymatic activities of SOD and GPx to
      almost control levels, in addition, MDA and caspase-3 activity decrease while T
      increase significantly as compared with untreated diabetic group. Prominent
      reduction of germ cell apoptosis was found in diabetic rats supplemented with
      antioxidants. An important role of testicular oxidative damage and germ cell
      apoptosis in diabetes-induced infertility could be suggested, treatment with
      antioxidants has a protective effect by restoring SOD and GPx antioxidant
      enzymatic activity.

PMID- 21184213
TI  - A new long terminal repeat (LTR) sequence allows to identify J genome from J S
      and St genomes of Thinopyrum intermedium.
AB  - A repetitive sequence of 491 bp, named pMD232-500, was isolated from S. cereale
      cv. Kustro using wheat SSR marker Xgwm232. GenBank BLAST search revealed that the
      sequence of pMD232-500 was highly similar to a part of retrotransposon Nusif-1.
      Fluorescence in situ hybridization (FISH) analysis using pMD232-500 as probe
      indicated that only 14 Thinopyrum intermedium chromosomes and all the chromosomes
      of S. cereale cv. Kustro bear FISH signals, however, no FISH signals were
      observed on Dasypyrum villosum chromosomes. In addition, the FISH signals were
      distributed on whole arms except their terminal regions. Further genomic in situ
      hybridization (GISH) analysis using genomic DNA from Pseudoroegneria spicata
      indicated that the 14 Th. intermedium chromosomes bearing FISH signals should
      belong to J genome. Thereafter, the repetitive elements pMD232-500 showed the
      unambiguous features of genomic constitution of Th. intermedium. In addition, the
      results in the present study have indicated the similarity of genomes from Th.
      intermedium and S. cereale.

PMID- 21184214
TI  - The association between chronic illness, multimorbidity and depressive symptoms
      in an Australian primary care cohort.
AB  - PURPOSE: To assess the link between multimorbidity, type of chronic physical
      health problems and depressive symptoms METHOD: The study was a cross-sectional
      postal survey conducted in 30 General Practices in Victoria, Australia as part of
      the diamond longitudinal study. Participants included 7,620 primary care
      attendees; 66% were females; age range from 18 to 76 years (mean = 51 years SD =
      14); 81% were born in Australia; 64% were married and 67% lived in an urban area.
      The main outcome measures include the Centre for Epidemiologic Studies Depression
      Scale (CES-D) and a study-specific self-report check list of 12 common chronic
      physical health problems. RESULTS: The prevalence of probable depression
      increased with increasing number of chronic physical conditions (1 condition:
      23%; 2 conditions: 27%; 3 conditions: 30%; 4 conditions: 31%; 5 or more
      conditions: 41%). Only 16% of those with no listed physical conditions recorded
      CES-D scores of 16 or above. Across the listed physical conditions the prevalence
      of 'probable depression' ranged from 24% for hypertension; 35% for emphysema; 35%
      for dermatitis to 36% for stroke. The dose-response relationship is reduced when
      functional limitations and self-rated health are taken into account, suggesting
      that these factors mediate the relationship. CONCLUSIONS: A clear dose-response
      relationship exists between the number of chronic physical problems and
      depressive symptoms. The relationship between multimorbidity and depression
      appears to be mediated via self-perceived health related quality of life. Primary
      care practitioners will identify more cases of depression if they focus on those
      with more than one chronic health problem, no matter what the problems may be,
      being especially aware in the group who rate their health as poor/fair.

PMID- 21184215
TI  - Random transposon mutagenesis of Verrucomicrobium spinosum DSM 4136(T).
AB  - The Verrucomicrobia are a bacterial group of growing interest due to their
      environmental ubiquity as free-living and host-associated microbes. They also
      exhibit an unusual compartmentalized cell plan, shared with members of
      neighboring phyla that include the Planctomycete bacteria. However,
      Verrucomicrobia are currently difficult to study, due to a lack of available
      genetic tools that would permit robust testing of hypotheses formulated from
      ecological and genomic data. To our knowledge, there are no published studies
      describing the transformation of exogenous DNA into any members of the
      Verrucomicrobia (or the neighboring phylum containing Planctomycetes). Here, we
      present a procedure for the transformation of DNA into Verrucomicrobium spinosum
      DSM 4136(T) via electroporation and the first description of a random transposon
      mutant library in this organism. We anticipate that this approach could be
      applied successfully to other Verrucomicrobia, providing opportunities to test
      the role of predicted gene function in ecological interactions and identify genes
      associated with the distinctive Planctomycete-Verrucomicrobial cell plan.

PMID- 21184216
TI  - Pseudomonas aeruginosa aerobic fatty acid desaturase DesB is important for
      virulence factor production.
AB  - Unsaturated fatty acids (UFAs) play a pivotal role in maintaining a functional
      cellular membrane in response to changes in environmental factors. Unlike in
      other gram-negative bacteria, in Pseudomonas aeruginosa, UFA synthesis is
      governed by 2 pathways: (1) the anaerobic FabAB-mediated pathway and (2) the
      aerobic inducible DesA/DesB desaturase pathway. Although fatty acids are
      functional constituents of several known virulence factors, the roles of
      Pseudomonas aeruginosa fatty acid synthesis enzymes in virulence factor
      production and pathogenesis have not yet been examined. Previous studies have
      shown that the mycobacterial DesA1 and DesA3 proteins are required for full
      virulence. Therefore, we assessed the effect, if any, of mutations affecting the
      various UFA synthesis enzymes on virulence factor production. Testing of
      individual mutations or combinations of mutations revealed that desB mutants were
      severely deficient in the production of proteolytic enzymes, pyocyanin, and
      rhamnolipid. In addition, the desB mutants showed impaired swarming and twitching
      motilities and reduced virulence in the Caenorhabditis elegans infection model.
      Taken together, these results demonstrate that DesB is not only a fatty acid
      desaturase but also a factor required for full virulence in Pseudomonas
      aeruginosa. DesB may thus constitute a novel drug target.

PMID- 21184217
TI  - Two putative histidine kinases are required for cyst formation in Rhodospirillum
      Centenum.
AB  - The photosynthetic bacterium, Rhodospirillum centenum, has a flexible life cycle
      that permits it to survive starvation as dormant cyst cells. Previous studies
      have identified some of the key regulators for encystment and demonstrated that
      the control of development is intricate. This complexity may arise from the need
      to integrate several environmental signals to mediate a switch from one mode of
      energy metabolism to another and to ensure that a transition to dormancy is
      initiated only when necessary. We searched for additional regulators of
      development by screening for encystment deficient strains after subjecting wild
      type R. centenum to mini-Tn5 mutagenesis. Analysis of "hypo-cyst" strains led to
      the identification of two genes that encode putative hybrid histidine kinases
      (cyd1 and cyd2). Cells with deletions of either gene fail to form cysts under
      conditions that normally induce development. Furthermore, the deletion strains
      exhibit altered swarming behavior suggesting that Cyd1 and Cyd2 affect behaviors
      utilized when the organism is attached to a substrate.

PMID- 21184218
TI  - Cloning and molecular analysis of a mannitol operon of phosphoenolpyruvate
      dependent phosphotransferase (PTS) type from Vibrio cholerae O395.
AB  - A putative mannitol operon of the phosphoenolpyruvate phosphotransferase (PTS)
      type was cloned from Vibrio cholerae O395, and its activity was studied in
      Escherichia coli. The 3.9-kb operon comprising three genes is organized as
      mtlADR. Based on the sequence analysis, these were identified as genes encoding a
      putative mannitol-specific enzyme IICBA (EII(Mtl)) component (MtlA), a mannitol-1
      phosphate dehydrogenase (MtlD), and a mannitol operon repressor (MtlR). The
      transport of [(3)H]mannitol by the cloned mannitol operon in E. coli was 13.8 +/-
      1.4 nmol/min/mg protein. The insertional inactivation of EII(Mtl) abolished
      mannitol and sorbitol transport in V. cholerae O395. Comparison of the mannitol
      utilization apparatus of V. cholerae with those of Gram-negative and Gram
      positive bacteria suggests highly conserved nature of the system. MtlA and MtlD
      exhibit 75% similarity with corresponding sequences of E. coli mannitol operon
      genes, while MtlR has 63% similarity with MtlR of E. coli. The cloning of V.
      cholerae mannitol utilization system in an E. coli background will help in
      elucidating the functional properties of this operon.

PMID- 21184219
TI  - Behavioral evidence for left-hemisphere specialization of motor planning.
AB  - Recent studies suggest that the left hemisphere is dominant for the planning of
      motor actions. This left-hemisphere specialization hypothesis was proposed in
      various lines of research, including patient studies, motor imagery studies, and
      studies involving neurophysiological techniques. However, most of these studies
      are primarily based on experiments involving right-hand-dominant participants.
      Here, we present the results of a behavioral study with left-hand-dominant
      participants, which follows up previous work in right-hand-dominant participants.
      In our experiment, participants grasped CD casings and replaced them in a
      different, pre-cued orientation. Task performance was measured by the end-state
      comfort effect, i.e., the anticipated degree of physical comfort associated with
      the posture that is planned to be adopted at movement completion. Both left- and
      right-handed participants showed stronger end-state comfort effects for their
      right hand compared to their left hand. These results lend behavioral support to
      the left-hemisphere-dominance motion-planning hypothesis.

PMID- 21184220
TI  - Appetite at high altitude: an fMRI study on the impact of prolonged high-altitude
      residence on gustatory neural processing.
AB  - Regulation of food intake is very important for health. It has been reported that
      people have decreased appetite at high altitude (HA). The current study recruited
      long-term HA residents to participate in an fMRI experiment which involved food
      craving. Result shows that the HA group showed decreased activation in the neural
      circuit for food craving, accompanied by decreased activation in regions for
      cognitive control and increased activation in regions for emotional processing.
      Such results also reflect the decreased gray matter volume and the hypometabolism
      mechanism under prolonged hypoxia stress at HA.

PMID- 21184221
TI  - Distal locking stem for revision femoral loosening and peri-prosthetic fractures.
AB  - Revision total hip arthroplasty in the setting of a large proximal femoral
      deficiency or a peri-prosthetic fracture remains a challenging problem. We
      describe the development, surgical technique and the use of cementless revision
      stems with distal inter-locking screws to provide immediate stability of the
      femoral implant. Results were assessed in a large multicentre French study
      conducted with the french hip and knee surgery society (SFHG). We retrospectively
      reviewed 725 revisions using interlocking stems from 14 French orthopaedic
      departments. Seven different stems were used in this series. In-patient records
      were retrieved, and in addition to demographic data the indication for revision,
      the preoperative and postoperative PMA and Harris hip scores were documented. The
      bone deficiency was classified on the basis of the French National Orthopaedic
      Meeting (SOFCOT) classification. Intraoperative complications and problems if any
      were retrieved from operative notes. Clinical status and radiographs at the final
      follow-up were evaluated, paying special attention to the metaphyseal filling
      index. Average follow-up was 4.5 years. As for the clinical results, the mean
      Harris hip score at last follow-up was 81. Therefore, it increased by an average
      of 31 points. Bone reconstruction was assessed on the cortico-medullary index in
      the metaphyseal area and at mid-shaft increasing from 36 to 45 and 54 to 63,
      respectively. Radiologically, 637 implants were stable, and 40 demonstrated
      subsidence. Forty-eight implants have been revised. We found a significant
      relation between the metaphyseal filling index, the stability of the stem and the
      quality of bone reconstruction. Results were analysed with respect to three
      groups of stems: group 1 was a straight, partially HA-coated implant; group 2 was
      a curved, fully HA-coated implant; and group 3 was a curved, partially-coated
      implant. Group 1 showed a significantly higher rate of failure when compared with
      the others types of implants. Group 2 had better functional results than group 3,
      which in turn reported better results than group 1. With regard to implant
      fixation, group 2 had significantly better results. Both groups 2 and 3 induced
      less thigh pain than group 1. The distal interlocking stem has shown promising
      results for femoral revisions. The advantages are initial axial and rotational
      stability and consistent bony in-growth owing to hydroxyapatite coating. Distal
      locked stems are mainly indicated to treat complex femoral revision with severe
      bone loss and peri-prosthetic fractures.

PMID- 21184222
TI  - Surgical treatment of thoracic outlet syndrome in young adults: single centre
      experience with minimum three-year follow-up.
AB  - Thoracic outlet syndrome is an often misdiagnosed syndrome which consists of a
      neurovascular compression at the upper thoracic outlet. The clinical presentation
      can be variable, ranging from mild symptoms to venous thrombosis and muscle
      atrophy. Many aetiologies, both congenital and acquired, related either to bony
      or soft tissue anomalies, have been associated with this syndrome. As a
      consequence, the diagnosis is often challenging and sometimes it can be obtained
      only with surgical exploration. Additionally, no specific clinical test is
      considered diagnostic of thoracic outlet syndrome. However, the recent advances
      in imaging techniques together with a careful clinical evaluation give the
      surgeon the chance to recognize the constricting anatomy before surgery in many
      cases. No standard surgical procedure has been identified; however, in literature
      the largest series have been treated with transaxillary first rib resection. Here
      we report our experience in the surgical treatment of this syndrome with a
      minimum follow-up of three years. Our approach consists of performing a
      supraclavicular decompression without routine first rib resection. This allows
      for identifying and removing the constricting anatomy in most cases, with
      satisfactory results in 96.9% of patients and a low complication rate.

PMID- 21184223
TI  - The dual mobility socket concept: experience with 668 cases.
AB  - Long-term results of a retrospective series of primary arthroplasty with the
      original cementless dual mobility socket (A) and the midterm results with the
      second generation (B) are reported. In series A (follow-up 16.5 years) 437 total
      hip arthroplasties (THA) were included and in series B (follow-up five years) 231
      hips. The 15-year survival rate was 84.4 +/- 4.5% (revision for any reason as
      endpoint); 30 hips (6.8%) were revised for aseptic loosening. Five THA were
      revised for dislocation: two early and three after ten years or more. With the
      second generation socket neither dislocation nor revision for mechanical reasons
      were observed. The survival rate was 99.6 +/- 0.4% (revision for any reason). The
      prevalence of revision for dislocation was very low in our series. This concept
      does not avoid wear and aseptic loosening, especially in young active patients,
      but the long-term stability has been confirmed. Dual mobility can be recommended
      for patients over 70 years of age and for younger patients with high risk of
      dislocation.

PMID- 21184224
TI  - Endovascular tubular stent-graft placement for isolated iliac artery aneurysms.
AB  - PURPOSE: To evaluate the safety, efficacy, and mid-term outcomes of endovascular
      tubular stent-graft placement for repair of isolated iliac artery aneurysms
      (IAAs). MATERIALS AND METHODS: Between January 2002 and March 2010, 20 patients
      (7 women and 13 men; mean age 74 years) underwent endovascular repair of 22
      isolated IAAs. Two patients underwent endovascular repair for bilateral
      aneurysms. Ten para-anastomotic aneurysms (45%) developed after open abdominal
      aortic aneurysm (AAA) repair with an aorto-iliac graft, and 12 were true
      aneurysms (55%). Eleven straight and 11 tapered stent-grafts were placed.
      Contrast-enhanced computed tomography (CT) was performed to detect complications
      and evaluate aneurysmal shrinkage at week 1, 3, 6, and 12 months and once every
      year thereafter. Non-contrast-enhanced CT was performed in seven patients with
      chronic kidney disease. RESULTS: All procedures were successful, without serious
      complications, during the mean (range) follow-up period of 746 days (47-2651).
      Type II endoleak not requiring treatment was noted in one patient. The mean (SD)
      diameters of the true and para-anastomotic aneurysms significantly (p < 0.05)
      decreased from 42.0 (9.3) to 36.9 (13.6) mm and from 40.1 (13.0) to 33.6 (15.8)
      mm, respectively; the mean (SD) shrinkage rates were 15.1% (20.2%) and 18.9%
      (22.4%), respectively. The primary patency rate was 100%, and no secondary
      interventions were required. Four patients (21%) developed transient buttock
      claudication, and one patient (5%) developed colorectal ischaemia, which was
      treated conservatively. CONCLUSION: Endovascular tubular stent-graft placement
      for the repair of isolated IAAs is safe and efficacious. Tapered stent-grafts of
      various sizes are required for accurate placement.

PMID- 21184225
TI  - Splenic artery syndrome after orthotopic liver transplantation: treatment with
      the Amplatzer vascular plug.
AB  - PURPOSE: To evaluate the safety and efficacy of the Amplatzer vascular plug (AVP)
      for embolization of the splenic artery in patients with hepatic hypoperfusion
      after orthotopic liver transplantation (OLT). MATERIALS AND METHODS: Thirteen
      patients (9 men and 4 women) with a mean age of 56 years (range 22-70) who
      developed splenic artery syndrome after OLT with decreased liver perfusion and
      clinically relevant impairment of liver function (increased transaminase or serum
      bilirubin levels, thrombocytopenia, and/or therapy-refractory ascites) were
      treated by embolization of the proximal third of the splenic artery using the
      AVP. The plugs ranged in diameter from 6 to 16 mm, and they were introduced
      through femoral (n = 9), axillary (n = 3), or brachial (n = 1) access using a 5F
      or 8F guiding catheter. RESULTS: The plugs were successfully placed, and complete
      occlusion of the splenic artery was achieved in all patients. Placement of two
      plugs was necessary for complete occlusion in 3 of the 13 patients. Occlusion
      took on average 10 min (range 4-35). There was no nontarget embolization or plug
      migration into more distal segments of the splenic artery. All patients showed
      improved arterial perfusion, including the liver periphery, on postinterventional
      angiogram. After embolization, liver function parameters (transaminase and
      bilirubin levels) improved with normalization of concomitant thrombocytopenia and
      a decrease in ascites volume. CONCLUSION: Our initial experience in a small
      patient population with SAS suggests that the AVP enables precise embolization of
      the proximal splenic artery, thus providing safe and effective treatment for poor
      liver perfusion after OLT due to SAS.

PMID- 21184226
TI  - Percutaneous transluminal angioplasty of hepatic artery stenosis in patients
      after orthotopic liver transplantation: mid-term results.
AB  - PURPOSE: This study was designed to present our experience with percutaneous
      treatment of hepatic artery stenosis in orthotopic liver transplant patients and
      to evaluate the efficacy, technical outcomes, and mid-term clinical results of
      the procedure. METHODS: Twenty-two percutaneous transluminal angioplasties (PTAs)
      were performed in 19 liver transplant recipients at our institution between 1998
      and 2010. Stents were placed into the hepatic/celiac artery in 16 PTAs, but
      balloon dilatation alone was performed in 6 because of the anatomical condition
      of the vessel. PTA/stenting was indicated in 17 patients because of elevated
      liver enzymes; 2 patients were asymptomatic. The objective of treating stenosis
      was prevention of long-term complications, including thrombosis. RESULTS:
      Technical success was achieved in all patients. There was only one complication:
      dissection of the treated artery without any subsequent adverse effects. In all
      patients, elevated liver enzyme levels improved after treatment. No restenosis
      was observed in any patient during a mean follow-up of 2.6 years (1 month to 5.5
      years). CONCLUSIONS: Percutaneous angioplasty/stent placement is a safe method
      for the treatment of hepatic artery stenosis after orthotopic liver
      transplantation, with a high technical success rate and promising mid-term
      results.

PMID- 21184227
TI  - Augmentation of chemotherapeutic infusion effect by TSU-68, an oral targeted
      antiangiogenic agent, in a rabbit VX2 liver tumor model.
AB  - PURPOSE: This study was designed to investigate the in vivo effects of
      combination therapy with TSU-68 and chemotherapeutic infusion in a rabbit VX2
      liver tumor model. METHODS: This study was approved by the animal care committee
      at our institute. Three weeks before chemotherapeutic infusion, VX2 carcinoma was
      implanted into the livers of 32 rabbits. One week after chemotherapeutic
      infusion, vehicle was administered orally for 3 weeks in the control group (n =
      16), and TSU-68 was administered orally at a daily dose of 200 mg/kg for 3 weeks
      in the treated group (n = 16). Computed tomography (CT) was performed before and
      1, 2, 3, and 4 weeks after chemotherapeutic infusion. Tumor response was assessed
      according to the Response Evaluation Criteria in Solid Tumors (RECIST) on CT
      scan. The maximum thickness of viable tumor was measured on microscopic sections.
      RESULTS: According to the RECIST, stable disease was observed in 9 (56%) rabbits
      and progressive disease in 7 (44%) in the control group, whereas partial response
      was observed in 1 (6%) rabbit and stable disease in 15 (94%) in the treated
      group. On pathologic examination, a viable lesion was present in 12 (75%) rabbits
      in the control group and in 6 (38%) rabbits in the treated group (P = 0.073). The
      mean maximum thickness of viable tumor in the treated group was significantly
      smaller than that in the control group (0.74 mm vs. 3.39 mm; P = 0.02).
      CONCLUSIONS: Oral administration of TSU-68 augmented the effect of
      chemotherapeutic infusion in a rabbit VX2 liver tumor model.

PMID- 21184228
TI  - Safety profile of sequential transcatheter chemoembolization with DC BeadTM:
      results of 237 hepatocellular carcinoma (HCC) patients.
AB  - INTRODUCTION: Complications of chemoembolization performed with DC Bead(TM)
      loaded with doxorubicin (DEBDOX) of diameters 100-300 MUm and 300-500 MUm are
      presented in this paper. These diameters are currently the smallest available in
      drug-eluting technology. METHODS: Included are 237 patients who were treated with
      sequential DEBDOX with doxorubicin loaded at 37.5 mg/ml of DC Bead. The National
      Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0)
      were used to categorize complications. RESULTS: Thirty-day mortality was 1.26%
      (3/237). Incidence of grade 5 complications was 1.26% (3/237). Overall, grade 4
      complications resulted in 5.48% (13/237) (irreversible liver failure,
      cholecystitis). Grade 2 liver function deterioration developed in 10 patients
      (4.2%). Cholecystitis/grade 2 and 4 incidents were observed in 3.6-5.06% across
      sessions (overall 13 patients; 5.48%). Postembolization Syndrome (PES) grade 1 or
      2 was observed in up to 86.5%; however, grade 2 was observed in 25-42.19% across
      treatments. Pleural effusion was seen in eight patients (overall 3.37%; grade 1
      in 1.8-3.7% across treatments; grade 3 in 0.42%). Grade 1 procedure-related
      laboratory pancreatitis was seen in 0.45%, and grade 2 gastrointestinal bleeding
      was seen in 0.84%. Procedure-associated skin erythema/grade 1 was seen in 0.84%.
      There was no correlation of liver failure or transient liver function
      deterioration with the diameter of the beads (p = 0.25-0.37 and p = 0.14-0.89,
      respectively). Stratifying with the diameter of the beads correlation values was:
      for cholecystitis (p = 0.11-0.96 across treatments), PES (p = 0.35-0.83),
      temporary/grade 1 elevation of liver enzymes (p = 0.002-0.0001), and bilirubin (p
      = 0.04-0.99). CONCLUSIONS: DEBDOX chemoembolization is safe and small calibres do
      not result in increased complication rates compared with results of series using
      larger diameters of beads.

PMID- 21184229
TI  - Sonication-assisted Agrobacterium rhizogenes-mediated transformation of Verbascum
      xanthophoeniceum Griseb. for bioactive metabolite accumulation.
AB  - An efficient protocol for the establishment of transformed root culture of
      Verbascum xanthophoeniceum using sonication-assisted Agrobacterium rhizogenes
      mediated transformation is reported. Only 10 days after the inoculation with A.
      rhizogenes ATCC 15834 and 45 s ultrasound exposure, hairy roots appeared on 75%
      of the Verbascum leaves. Ten hairy root lines were isolated, although only half
      of them were free of bacterial contamination and started growing when excised
      from mother explants. The transgenic nature of the most vigorously growing hairy
      root clones (VX1 and VX6) was confirmed by polymerase chain reaction. Under
      submerged cultivation both hairy root clones accumulated high biomass amounts
      (12.8 and 14.3 g L(-1), respectively) and significant amounts of bioactive
      phenylethanoid glycoside verbascoside (over 6-times more than in mother plant
      leaves). LC-APCI-MS analyses confirmed verbascoside accumulation in hairy root
      clones along with three other phenylethanoid glycosides (forsythoside B,
      leucosceptoside B and martynoside) and an iridoid glycoside aucubin. This is the
      first report on the induction of hairy roots of Verbascum plants.

PMID- 21184230
TI  - Production of marker-free disease-resistant potato using isopentenyl transferase
      gene as a positive selection marker.
AB  - The use of antibiotic or herbicide resistant genes as selection markers for
      production of transgenic plants and their continuous presence in the final
      transgenics has been a serious problem for their public acceptance and
      commercialization. MAT (multi-auto-transformation) vector system has been one of
      the different strategies to excise the selection marker gene and produce marker
      free transgenic plants. In the present study, ipt (isopentenyl transferase) gene
      was used as a selection marker gene. A chitinase gene, ChiC (isolated from
      Streptomyces griseus strain HUT 6037) was used as a gene of interest. ChiC gene
      was cloned from the binary vector, pEKH1 to an ipt-type MAT vector, pMAT21 by
      gateway cloning and transferred to Agrobacterium tumefaciens strain EHA105. The
      infected tuber discs of potato were cultured on hormone- and antibiotic-free MS
      medium. Seven of the 35 explants infected with the pMAT21/ChiC produced shoots.
      The same antibiotic- and hormones-free MS medium was used in subcultures of the
      shoots (ipt like and normal shoots). Molecular analyses of genomic DNA from
      transgenic plants confirmed the integration of gene of interest and excision of
      the selection marker in 3 of the 7 clones. Expression of ChiC gene was confirmed
      by Northern blot and western blot analyses. Disease-resistant assay of the marker
      free transgenic, in vitro and greenhouse-grown plants exhibited enhanced
      resistance against Alternaria solani (early blight), Botrytis cinerea (gray mold)
      and Fusarium oxysporum (Fusarium wilt). From these results it could be concluded
      that ipt gene can be used as a selection marker to produce marker-free disease
      resistant transgenic potato plants on PGR- and antibiotic-free MS medium.

PMID- 21184231
TI  - Natural genetic and induced plant resistance, as a control strategy to plant
      parasitic nematodes alternative to pesticides.
AB  - Plant-parasitic nematodes are pests of a wide range of economically important
      crops, causing severe losses to agriculture. Natural genetic resistance of plants
      is expected to be a valid solution of the many problems nematodes cause all over
      the world. Progress in resistance applications is particularly important for the
      less-developed countries of tropical and subtropical regions, since use of
      resistant cultivars may be the only possible and economically feasible control
      strategy in those farming systems. Resistance is being considered of particular
      importance also in modern high-input production systems of developed countries,
      as the customary reliance on chemical nematicides has been restricted or has come
      to an end. This review briefly describes the genetic bases of resistance to
      nematodes in plants and focuses on the chances and problems of its exploitation
      as a key element in an integrated management program. Much space is dedicated to
      the major problem of resistance durability, in that the intensive use of
      resistant cultivars is likely to increasingly induce the selection of virulent
      populations able to "break" the resistance. Protocols of pest-host suitability
      are described, as bioassays are being used to evaluate local nematode populations
      in their potential to be selected on resistant germplasm and endanger resistant
      crops. The recent progress in using robust and durable resistances against
      nematodes as an efficient method for growers in vegetable cropping systems is
      reported, as well as the possible use of chemicals that do not show any
      unfavorable impact on environment, to induce in plants resistance against plant
      parasitic nematodes.

PMID- 21184232
TI  - Metabolic engineering of artemisinin biosynthesis in Artemisia annua L.
AB  - Artemisinin, a sesquiterpene lactone isolated from the Chinese medicinal plant
      Artemisia annua L., is an effective antimalarial agent, especially for multi-drug
      resistant and cerebral malaria. To date, A. annua is still the only commercial
      source of artemisinin. The low concentration of artemisinin in A. annua, ranging
      from 0.01 to 0.8% of the plant dry weight, makes artemisinin relatively expensive
      and difficult to meet the demand of over 100 million courses of artemisinin-based
      combinational therapies per year. Since the chemical synthesis of artemisinin is
      not commercially feasible at present, another promising approach to reduce the
      price of artemisinin-based antimalarial drugs is metabolic engineering of the
      plant to obtain a higher content of artemisinin in transgenic plants. In the past
      decade, we have established an Agrobacterium-mediated transformation system of A.
      annua, and have successfully transferred a number of genes related to artemisinin
      biosynthesis into the plant. The various aspects of these efforts are discussed
      in this review.

PMID- 21184233
TI  - [Biologics in ophthalmology].

PMID- 21184234
TI  - [A history of joint puncture and injection].
AB  - Up until the middle of the 20th century joint puncture was considered a dangerous
      surgical intervention performed primarily to drain pus. The differential
      diagnostic significance of synovial analysis only became clear in the second half
      of the 20th century. Thus it became possible to reliably distinguish between
      inflammatory and non-inflammatory diseases, and establish whether arthritides are
      bacterial or crystal-induced. Attempts to inject disinfecting or anti
      inflammatory solutions into the joint go back to the end of the 19th century. In
      the mid 20th century, cortisone became the panacea of intraarticular therapy.
      After surgeons at the end of the 19th century succeeded in surgically removing
      the inflamed synovium, internal medicine specialists attempted to destroy the
      synovial membrane by injecting it with various chemicals around the mid 20th
      century; however, hardly any of these substances survived. Only with "internal
      radiation" by injecting radionuclides was a breakthrough seen in the middle of
      the 20th century. Since then radiosynoviorthesis and synovialectomy have become
      standard methods in the treatment of chronic inflammatory joint disease.

PMID- 21184235
TI  - Plastic repair for a case with synpolydactyly.
AB  - On March 23, 2010, we successfully treated a boy with synpolydactyly who had a
      total of 31 fingers and toes. Although there was bone syndactyly both the hands
      of the boy, one-step correction of four extremities was successful, this
      operation lasted 5 h and 20 min and intraoperative bleeding was about 50 ml. Skin
      grafting was successful after operation and all incisions healed well. The
      appearance and function of hands and feet were satisfactory.

PMID- 21184236
TI  - Partial, selective survival of nitrergic neurons in chagasic megacolon.
AB  - One frequent chronic syndrome of Chagas' disease is megacolon, an irreversible
      dilation of a colonic segment. Extensive enteric neuron loss in the affected
      segment is regarded as key factor for deficient motility. Here, we assessed the
      quantitative balance between cholinergic and nitrergic neurons representing the
      main limbs of excitatory and inhibitory colonic motor innervation, respectively.
      From surgically removed megacolonic segments of four patients, each three
      myenteric wholemounts (from non-dilated oral, megacolonic and non-dilated anal
      parts) was immunohistochemically triple-stained for choline acetyltransferase,
      neuronal nitric oxide synthase (NOS) and the panneuronal human neuronal protein
      Hu C/D. Degenerative changes were most pronounced in the megacolonic and anal
      regions, e.g. bulked, honeycomb-like ganglia with few neurons which were partly
      enlarged or atrophic or vacuolated. Neuron counts from each 15 ganglia of 12
      megacolonic wholemounts were compared with those of 12 age- and region-matched
      controls. Extensive neuron loss, mainly in megacolonic and anal wholemounts, was
      obvious. In all three regions derived from megacolonic samples, the proportion of
      NOS-positive neurons (control: 55%) was significantly increased: in non-dilated
      oral parts to 61% (p = 0.003), in megacolonic regions to 72% (p < 0.001) and in
      non-dilated anal regions to 78% (p < 0.001). We suggest the chronic dilation of
      megacolonic specimens to be due to the preponderance of the nitrergic, inhibitory
      input to the intestinal muscle. However, the observed neuronal imbalance was not
      restricted to the dilated regions: the non-dilated anal parts may be innervated
      by ascending, cholinergic axons emerging from less affected, more anally located
      regions.

PMID- 21184237
TI  - Expression pattern of claudins 1 and 3-an auxiliary tool in predicting behavior
      of mucoepidermoid carcinoma of salivary gland origin.
AB  - Claudins (CLDNs) are a family of membrane proteins important for permeability of
      tight junctions. They have also been implicated in carcinogenesis and tumor
      progression. We analyzed patterns of distribution and intensity of expression of
      CLDNs 1, 3, 4, and 7 in mucoepidermoid carcinoma (MEC) of salivary gland in 39
      patients. Correlations between the expression of CLDNs, tumor grade, and survival
      were explored. In immunohistochemical analysis, high expression of CLDN 1 was
      seen in low-grade MEC, and it appeared to be a suitable auxiliary marker of good
      prognosis. It classified MEC similarly to histological grading in 89.7% of cases
      (p = 0.001). High CLDN 3 expression was seen in intermediate- and high-grade MEC,
      while it was low in low-grade MEC. CLDN 3 intensity correctly categorized tumors
      into grades in 71.8% of cases (p = 0.017). However, in multivariate analysis CLDN
      1 and CLDN 3 did not achieve significance over tumor grade in predicting patient
      behavior. We conclude that analysis of staining intensities of CLDN 1 and 3 is
      useful as an auxiliary diagnostic and prognostic tool in patients with salivary
      gland MEC.

PMID- 21184238
TI  - Treeline proximity alters an alpine plant-herbivore interaction.
AB  - Rising treeline threatens the size and contiguity of alpine meadows worldwide. As
      trees encroach into previously open habitat, the movement and population dynamics
      of above-treeline alpine species may be disrupted. This process is well
      documented in studies of the Rocky Mountain apollo butterfly (Parnassius
      smintheus). However, subtler consequences of treeline rise remain poorly
      understood. In this study, we examine whether treeline proximity affects feeding
      behaviour of P. smintheus larvae, due to altered habitat affecting the
      distribution and availability of their host plant, lance-leaved stonecrop (Sedum
      lanceolatum). Understanding differential larval exploitation of food resources in
      relation to the treeline is an important step in predicting the consequences of
      continued treeline rise. Parnassius smintheus larvae feed more intensively on S.
      lanceolatum away from the treeline despite the relative paucity of hosts in these
      areas, and despite higher fitness penalties associated with the plant's herbivory
      induced chemical defenses. Sedum lanceolatum growing near the treeline is less
      attractive, and therefore represents a less significant resource for P. smintheus
      larvae than its abundance might imply. If treeline rise continues, we suggest
      that this pattern of altered resource exploitation may represent a mechanism by
      which larvae are adversely affected even while adult movement among and within
      meadows appears sufficient for maintaining population health, and total host
      availability seems ample.

PMID- 21184239
TI  - Role of the podocyte in proteinuria.
AB  - In recent years, the podocyte, with its elaborate cytoarchitecture and slit
      diaphragm, has been the focus of extensive research, yet its precise role in the
      glomerular filtration barrier is still debated. There are puzzling observations
      indicating that a comprehensive mechanistic model for glomerular filtration is
      still necessary. There is no doubt that podocytes are essential for glomerular
      filtration barrier integrity. However, most albumin never reaches the podocyte
      because it is prevented from entering the glomerular filter at the endothelium
      level. Another puzzling observation is that the glomerular filter never clogs
      despite its high load of several kilograms of plasma proteins per day. Recently,
      we proposed a novel model in which an electrical potential difference is
      generated across the glomerular filtration barrier by filtration. The model
      offers novel potential solutions to some of the riddles regarding the glomerular
      filter.

PMID- 21184240
TI  - Cyclosporin A therapy for Henoch-Schonlein nephritis with nephrotic-range
      proteinuria.
AB  - To evaluate the therapeutic role of cyclosporin A (CyA) for the treatment of
      Henoch-Schonlein nephritis (HSN), 29 patients (18 boys, 11 girls) with nephrotic
      range proteinuria were analyzed retrospectively. Mean age was 8.6 years (range
      2.0-15.5 years) at diagnosis of Henoch-Schonlein purpura (HSP). All patients had
      developed the nephrotic-range proteinuria at a mean interval of 4.4 months (range
      0-50.7 months) after the diagnosis of HSP. Mean duration of CyA treatment was
      12.3 months (range 2.6-55.0 months). Mean follow-up times were 3.7 years (range
      1.2-12.9 years) from the beginning of the CyA treatment. Steroids were tapered
      off and stopped gradually after initiation of CyA. All patients responded to the
      CyA treatment within a mean of 1.8 months (range 1 week to 3.5 months). Twenty
      three patients achieved stable remission with mean follow-up duration of 3.2
      years and 6 patients seemed to become CyA-dependent, since they developed
      proteinuria when the treatment was stopped. Renal function was preserved in all
      patients but one who developed end-stage renal disease after poor compliance with
      CyA. We concluded that CyA treatment for HSN showing nephrotic-range proteinuria
      is very effective and a safe method, although some patients become CyA-dependent.

PMID- 21184241
TI  - Expression and function of the Ets transcription factor pea3 during formation of
      zebrafish pronephros.
AB  - Polyomavirus enhancer activator 3 (Pea3), belonging to the PEA3 subfamily of Ets
      transcription factors, is essential for certain organogenesis in mammals.
      Previously, we found that pea3 correlated with wt1 expression and may contribute
      to nephrogenesis in rats. Here, we observed that pea3 was mainly expressed in the
      zebrafish pronephric glomerulus. We further performed functional analyses by in
      situ hybridization of pea3 in zebrafish embryos after pea3 messenger RNA (mRNA)
      overexpression and inhibition of double-target genes (pea3 and erm, another
      member of the PEA3 subfamily) by antisense morpholino-oligonucleotides (MO).
      Overexpression of pea3 induced abnormal pronephrogenesis. However, MO-pea3
      coinjected with MO-erm, but not alone, inhibited zebrafish pronephros
      development, and these defects were rescued by overexpression of the zebrafish
      wt1a gene. Thus, pea3 and erm are required for zebrafish pronephrogenesis and can
      functionally complement each other, and the wt1a gene may be one of their
      downstream targets.

PMID- 21184242
TI  - Sequence analysis of the replicase gene of 'sweet potato caulimo-like virus'
      suggests that this virus is a distinct member of the genus Cavemovirus.
AB  - Virion purification from indicator plants and partial sequencing of the replicase
      region of a 'sweet potato caulimo-like virus' (SPCV) isolate from Madeira,
      Portugal, are described. Phylogenetic analysis suggests that SPCV is a distinct
      member of the genus Cavemovirus (family Caulimoviridae). These results explain
      previous failed attempts to characterize SPCV based on antibodies or primers
      designed for other members of the Caulimoviridae. Using a quick DNA extraction
      protocol and PCR primers flanking the RT motif region, we were able to detect
      SPCV directly in sweet potato, thus saving considerable time during routine virus
      indexing.

PMID- 21184243
TI  - Inhibition of viral hemorrhagic septicemia virus replication using a short
      hairpin RNA targeting the G gene.
AB  - RNA interference (RNAi), a mechanism for post-transcriptional silencing of
      homologous genes by double-stranded RNA (dsRNA), has emerged as an antiviral
      strategy in animals. In this study, the epithelioma papulosum cyprini (EPC) cell
      line, in combination with a fugu-U6-promoter-driven shRNA construct designed
      against G gene, was used to investigate whether short hairpin RNA (shRNA) could
      inhibit viral hemorrhagic septicemia virus (VHSV) proliferation by sequence
      specific RNAi. The results showed that transfection with a shRNA-producing
      construct (shRNA-VG594) resulted in a sequence-specific knockdown of G gene mRNA
      in EPC cells. There were no significant differences in IFN-induced Mx1 gene
      expression among cells transfected with each shRNA vector including shRNA-VG594, 
      VG594sc (two nucleotides mismatch) and -EGFP (non-specific control), suggesting
      that knockdown of G gene expression was not due to an IFN response but instead by
      sequence-specific RNAi. Transfection of EPC cells with shRNA-VG594 conferred
      resistance to VHSV, and this anti-VHSV effect was not observed when using a two
      nucleotide-mismatched shRNA-VG594sc or a shRNA targeting EGFP. Furthermore, shRNA
      VG594 expressed in EPC cells did not confer protection against infectious
      hematopoietic necrosis virus (IHNV), suggesting sequence-specific RNAi-dependent
      suppression of viral replication.

PMID- 21184244
TI  - Complete genomic sequence of watermelon bud necrosis virus.

PMID- 21184245
TI  - Broad neutralizing antibody response and genetic variation in HIV-1 env genes in
      Koreans with primary HIV-1 infections.
AB  - To determine the neutralization profiles induced by HIV-1 Korean clade B, which
      has a monophyletic lineage and relative limited genetic diversity, we
      investigated the ability of HIV variants to elicit neutralizing antibodies in the
      immune response to primary infection. We selected seven Korean drug-naive
      subjects with an HIV-1 primary infection and did pseudovirion-based
      neutralization assays using env genes of Korean HIV origin. The neutralizing
      antibody responses to the Korean clade B showed broad reactivity to subtype B but
      a highly subtype-specific pattern. The lengths of the amino acid sequences and
      the PNGS numbers in the V1-V5 region were positively correlated with
      neutralization. These results imply that the genetic characteristics of HIV-1 env
      may affect neutralizing antibody responses in HIV-1-infected individuals. This is
      the first report describing the relationship between neutralizing antibody
      responses and HIV-1 genetic characteristics in Korean subjects. It can be useful
      for developing AIDS vaccines against HIV-1 subtype B strains.

PMID- 21184246
TI  - The prevalence of vitamin D deficiency in consecutive new patients seen over a 6
      month period in general rheumatology clinics.
AB  - The objectives of this study are to assess: (a) the prevalence of vitamin D
      deficiency among new patients attending rheumatology outpatient departments, (b)
      the age profile of these low vitamin D patients and (c) whether any diagnostic
      category had a particularly high number of vitamin D-deficient patients. All new
      patients seen consecutively in general rheumatology clinics between January to
      June 2007 inclusive were eligible to partake in this study, and 231 out of 264
      consented to do so. Parathyroid hormone, 25-hydroxyvitamin D, creatinine,
      calcium, phosphate, albumin and alkaline phosphatase levels were measured. We
      defined vitamin D deficiency as <=53 nmol/l and severe deficiency as <=25 nmol/l.
      Overall, 70% of 231 patients had vitamin D deficiency, and 26% had severe
      deficiency. Sixty-five percent of patients aged >=65 and 78% of patients aged
      <=30 years had low vitamin D levels. Vitamin D deficiency in each diagnostic
      category was as follows: (a) inflammatory joint diseases/connective tissue
      diseases (IJD/CTD), 69%; (b) soft tissue rheumatism, 77%; (c) osteoarthritis,
      62%; (d) non-specific musculoskeletal back pain, 75% and (e) osteoporosis, 71%.
      Seasonal variation of vitamin D levels was noted in all diagnostic groups apart
      from IJD/CTD group, where the degree of vitamin D deficiency persisted from late
      winter to peak summer. Very high prevalence of vitamin D deficiency was noted in
      all diagnostic categories (p = 0.006), and it was independent of age (p = 0.297).
      The results suggest vitamin D deficiency as a possible modifiable risk factor in
      different rheumatologic conditions, and its role in IJD/CTD warrants further
      attention.

PMID- 21184247
TI  - Arterial baroreflex modulation influences postural sway.
AB  - OBJECTIVE: Although considered mainly a random function, postural sway is
      influenced by physiological factors such as respiration. A direct effect of the
      autonomic nervous system (ANS) on posture has never been demonstrated. To test
      this hypothesis, we used a pure motion-independent autonomic stimulus (neck
      suction) to modulate the carotid baroreceptors on a broad frequency range,
      distinct from that of respiration. METHODS: Thirteen healthy subjects (age 26 +/-
      5 years) were studied upright, eyes closed, and on a force platform during
      controlled breathing (15 breath/min, 0.25 Hz), with and without stimulation of
      arterial baroreceptors by sinusoidal neck suction (0 to -30 mmHg pressure) at
      different frequencies (0.05, 0.10, 0.125, 0.15, 0.175, 0.20, 0.30 Hz), for eight
      periods lasting 2 min each. The increase in sway, R-R interval and blood pressure
      induced at each stimulation frequency was measured by spectral analysis. RESULTS:
      With neck suction, we observed a significant (p < 0.05) increase in oscillations
      synchronous in the R-R interval (from 0.10 to 0.20 Hz), systolic and diastolic
      blood pressure (from 0.05 to 0.15 Hz) and sway (from 0.10 to 0.30 Hz in both the
      antero-posterior and medio-lateral planes). Changes were greater in the left than
      in the right foot. CONCLUSION: Our study shows that postural sway is modulated by
      the ANS and is influenced by phasic stimulation of the arterial (carotid)
      baroreceptors. Our findings have potentially important clinical implications in
      the development of treatment strategies for pathological conditions in which
      alterations in posture and autonomic function coexist and could be mutually
      influenced.

PMID- 21184248
TI  - Reduced water induced skin wrinkling in congestive heart failure.
AB  - Water immersion skin wrinkling (WISW) of the fingertips may reflect central
      autonomic function. We found lower WISW in 60 heart failure patients versus
      controls (1.6+/-0.67 vs. 2.5+/-1.1, p<0.001), linking a cardiovascular disorder
      to reduced WISW.

PMID- 21184249
TI  - Seasonal influence of the surgical outcome after thoracic sympathectomy for
      hyperhidrosis.
AB  - Analyze the seasonal variation of the surgical results after sympathectomy
      through the seasons of the year. The surgical results are better in the spring,
      and the sudomotor reflex is worst in summer. Comparison of surgical results of
      distinct techniques should be done under the same climatic conditions.

PMID- 21184250
TI  - Comparative analysis of oxygen transfer rate distribution in stirred bioreactor
      for simulated and real fermentation broths.
AB  - Study of the distribution of the oxygen mass transfer coefficient, k (l) a, for a
      stirred bioreactor and simulated (pseudoplastic solutions of
      carboxymethylcellulose sodium salt) bacterial (P. shermanii), yeast (S.
      cerevisiae), and fungal (P. chrysogenum free mycelia) broths indicated
      significant variation of transfer rate with bioreactor height. The magnitude of
      the influence of the considered factors differed from one region to another. As a
      consequence of cell adsorption to bubble surface, the results indicated the
      impossibility of achieving a uniform oxygen transfer rate throughout the whole
      bulk of the microbial broth, even when respecting the conditions for uniform
      mixing. Owing to the different affinity of biomass for bubble surface, the
      positive influence of power input on k (l) a is more important for fungal broths,
      while increasing aeration is favorable only for simulated, bacterial and yeast
      broths. The influence of the considered factors on k (l) a were included in
      mathematical correlations established based on experimental data. For all
      considered positions, the proposed equations for real broths have the general
      expression [Formula in text] exhibiting good agreement with experimental results
      (with maximum deviations of +/- 10.7% for simulated broths, +/- 8.4% for P.
      shermanii, +/- 9.3% for S. cerevisiae, and +/- 6.6% for P. chrysogenum).

PMID- 21184251
TI  - High level phytase production by Aspergillus niger NCIM 563 in solid state
      culture: response surface optimization, up-scaling, and its partial
      characterization.
AB  - Phytase production by Aspergillus niger NCIM 563 was optimized by using wheat
      bran in solid state fermentation (SSF). An integrated statistical optimization
      approach involving the combination of Placket-Burman design (PBD) and Box-Behnken
      design (BBD) was employed. PBD was used to evaluate the effect of 11 variables
      related to phytase production, and five statistically significant variables,
      namely, glucose, dextrin, NaNO(3), distilled water, and MgSO(4) . 7H(2)O, were
      selected for further optimization studies. The levels of five variables for
      maximum phytase production were determined by a BBD. Phytase production improved
      from 50 IU/g dry moldy bran (DMB) to 154 IU/g DMB indicating 3.08-fold increase
      after optimization. A simultaneous reduction in fermentation time from 7 to 4
      days shows a high productivity of 38,500 IU/kg/day. Scaling up the process in
      trays gave reproducible phytase production overcoming industrial constraints of
      practicability and economics. The culture extract also had 133.2, 41.58, and
      310.34 IU/g DMB of xylanase, cellulase, and amylase activities, respectively. The
      partially purified phytase was optimally active at 55 degrees C and pH 6.0. The
      enzyme retained ca. 75% activity over a wide pH range 2.0-9.5. It also released
      more inorganic phosphorus from soybean meal in a broad pH range from 2.5 to 6.5
      under emulated gastric conditions. Molecular weight of phytase on Sephacryl S-200
      was approximately 87 kDa. The K (m) and V (max) observed were 0.156 mM and 220
      MUm/min/mg. The SSF phytase from A. niger NCIM 563 offers an economical
      production capability and its wide pH stability shows its suitability for use in
      poultry feed.

PMID- 21184252
TI  - Interaction of clozapine and its nitrenium ion with rat D2 dopamine receptors: in
      vitro binding and computational study.
AB  - The interaction of diazepine analogues like clozapine or olanzapine with D2
      receptor was greatly affected by a mixture of HRP/H(2)O(2) known to induce the
      formation of nitrenium ion. Unlike diazepine derivatives, the oxidative mixture
      had low impact on the affinity of oxa- and thiazepine derivatives such as
      loxapine, clothiapine or JL13 for the D2 receptor. Molecular docking simulations
      revealed a huge difference between the mode of interaction of clozapine nitrenium
      ion and the parent drug. Electronic and geometric changes of the tricyclic ring
      system caused by the oxidation appeared to prevent the compound finding the
      correct binding mode and could therefore explain the difference observed in
      binding affinities.

PMID- 21184253
TI  - Recurrent myocardial infarction associated with gefitinib therapy.
AB  - Gefitinib is an epidermal growth factor tyrosine kinase inhibitor used as a
      targeted chemotherapeutic agent in the treatment of lung cancer and other solid
      malignancies. Unlike other tyrosine kinase inhibitors, gefitinib is not
      recognized as having significant cardiotoxicity though it has been reported to be
      capable of potentiating ADP-induced activation and thromboxane A(2) generation in
      platelets which could promote thrombosis. We report a case of recurrent
      myocardial infarction with angiographically documented vulnerable plaque rupture
      in a patient receiving chronic gefitinib therapy for metastatic carcinoid tumor.
      Platelet function studies revealed marked ADP-induced platelet activation that
      was only suppressed by high-dose clopidogrel. Measurement of urine 11-dehydro
      thromboxane B(2) also indicated persistent thromboxane A(2) generation despite
      aspirin therapy, an emerging risk factor for adverse cardiovascular events.

PMID- 21184254
TI  - Phosphorylation of Caldesmon by PFTAIRE1 kinase promotes actin binding and
      formation of stress fibers.
AB  - Caldesmon (CaD) is an actin-binding protein that is capable of stabilizing actin
      filaments. Phosphorylation of CaD is widely accepted in the actin cytoskeletal
      modeling and promotion of cell migration. In this study, we show that CaD is a
      downstream phosphorylation substrate of PFTK1, a novel Cdc-2-related ser/thr
      protein kinase. Our study stemmed from an earlier investigation where we
      demonstrated that PFTK1 kinase conferred cell migratory advantages in human
      hepatocellular carcinoma (HCC) cells. Here, we showed that PFTK1-knockdown cells
      exhibited much reduced CaD phosphorylation and consequently caused dissociation
      of CaD from the F-actin fibers. The cellular localization of CaD was also altered
      in the absence of PFTK1. Immunofluorescence analysis revealed that PFTK1
      abrogated cells exhibited a diffused and blurred appearance of CaD localization,
      whereas intact co-localization with F-actins was apparent in PFTK1-expressing
      cells. Without the binding of CaD to actin, disappearance of actin stress fibers
      was also evident in PFTK1-abrogated cells. In addition, we found that CaD is also
      commonly up-regulated in HCC tumors when compared to adjacent non-malignant liver
      (P = 0.022). Taken together, our results highlight a novel biological cascade
      that involved the phosphorylation activation of CaD by PFTK1 kinase in promoting
      formation of actin stress fibers.

PMID- 21184255
TI  - RNA interference-mediated silencing of iASPP induces cell proliferation
      inhibition and G0/G1 cell cycle arrest in U251 human glioblastoma cells.
AB  - iASPP is an evolutionally conserved inhibitory member of the ASPP (apoptosis
      stimulating protein of p53) protein family. Overexpression of iASPP was observed
      in several types of human tumors, however, its role in tumorigenesis has not been
      fully clarified. To investigate the role of iASPP in human glioblastoma
      multiforme (GMB) progression, the authors employed lentivirus-mediated shRNA to
      silence endogenous iASPP expression and elucidated iASPP function by analysis of
      viability, colony formation, DNA synthesis, and cell cycle in p53-mutant
      glioblastoma cell line U251. iASPP was significantly and sustainably knocked down
      by iASPP-specific shRNA in U251 cells. Stable down-regulation of iASPP expression
      induced cell proliferation inhibition and G0/G1 cell cycle arrest by down
      regulation of cyclin D1 and up-regulation of p21(Waf1/Cip1). Thus, the findings
      not only provide a molecular basis for the role of iASPP in cell cycle
      progression of glioblastoma cells but also suggest a novel therapeutic target for
      the treatment of GBM.

PMID- 21184256
TI  - Tissue procurement strategies affect the protein biochemistry of human heart
      samples.
AB  - The ability to analyze the biochemical properties of human cardiac tissue is
      critical both to an understanding of cardiac pathology and also to the
      development of novel pharmacotherapies. However current strategies for tissue
      procurement are not uniform and are potentially biased. In this study we
      contrasted several commonly used approaches for tissue sampling in order to
      determine their impact on contractile protein biochemistry. Not surprisingly our
      results show that different tissue handling strategies have the potential to
      produce a wide variation in the phosphorylation and proteolysis of selected
      contractile proteins. However this was not uniform: phosphorylation of troponin I
      (TnI) and myosin light chain 2 (MLC2) varied significantly depending on approach
      whereas changes in desmin and myosin binding protein C (MyBP-C) were relatively
      unaffected. Moreover, some strategies increased whereas others reduced TnI
      phosphorylation, suggesting a dynamic balance between kinase and phosphatase
      activities. Overall, procurement strategies that involved maintenance of tissue
      in cardioplegia solution deviated most dramatically from prompt and rapid tissue
      immersion in liquid nitrogen.

PMID- 21184257
TI  - General guidelines for authors for submission of manuscripts that contain
      molecular biological content.
AB  - The Journal of Chemical Ecology (the Journal) has been publishing an increasing
      number of contributions that report experiments that use the methods of molecular
      biology. In 2004, a special issue of the Journal [JCE 30(12)] focused on
      molecular chemical ecology and documented the increasing trend of published
      submissions with molecular content (Seybold 2004). The guidelines presented here
      were developed to provide assistance to authors, with the goal of ensuring
      standardized and complete reporting of molecular information in the Journal. The
      fields of molecular biology and bioinformatics change rapidly as new technologies
      and protocols are continually developed and introduced. Thus, the Journal intends
      to revise and re-issue these guidelines periodically as significant changes in
      this area of science occur. Molecular biological content includes reports on
      specific nucleic acids and proteins involved in chemical ecological phenomena.
      The guidelines are separated into 3 parts: I. Types of Papers Published; II.
      Appropriate Nomenclature and Abbreviations; and III. Presentation of Molecular
      Biological Content.

PMID- 21184258
TI  - Flow injection small-volume fiber-optic pH sensor based on evanescent wave
      excitation and fluorescence determination.
AB  - A small-volume fiber-optic pH sensor (FOEWS) based on evanescent wave excitation
      is developed and evaluated. The sensor is simply fabricated by inserting a
      decladded optical fiber into a transparent capillary tube. A microchannel between
      the optical fiber and the capillary inner wall was formed and acted as flow cell
      for solution flowing through. The pH-sensitive fluorophore of fluorescein can be
      excited by the evanescent wave field produced on the fiber core surface to
      produce emission fluorescence. pH value was then sensed by its enhancing effect
      on the emission fluorescence intensity. The response range of the sensor is from
      pH 2.09 to pH 8.85 and the linear range is from pH 3.25 to 8.85. The proposed
      sensor has a small detection volume of 2.5 MUL and a short response time of 8 s.
      It has been applied to measure pH values of real water samples and was in good
      agreement with the results obtained by commercial pH meter.

PMID- 21184259
TI  - Solvatochromic and fluorescence behavior of sulfisoxazole.
AB  - The Fluorescence spectroscopic and solvatochromic behavior of Sulfisoxazole, a
      sulfa drug with antimicrobial activities, in various pure solvents of different
      polarity and hydrogen bonding capability is reported. The fluorescence emission
      spectrum of sulfisoxazole was found to be solvent polarity dependent, where a
      notable red shift in emission maximum was observed with increasing solvent
      polarity as well as hydrogen bonding capability. The effects of the latter two
      solvent parameters were quantitatively investigated using the methods of Lippert
      Mataga and solvatochromic comparison method (SCM) that is based on the Kamlet
      Taft equation. Particularly, the Lippert-Mataga method was applied to estimate
      the dipole moment of the excited state (MU(e)) upon plotting Stokes shift versus
      solvent polarizability (Deltaf), where a value of 11.54 Debye was obtained. On
      the other hand, applying the multiple regression analysis to the SCM method
      revealed that solvent polarizability (pi*) and hydrogen-bond donor capability
      (alpha) approximately equally stabilize sulfisoxazole in the excited state with
      minor destabilization contribution by the hydrogen-bond acceptor capability
      (beta). These findings revealed that the excited state of sulfisoxazole is
      stabilized by polar solvents, indicating that this drug molecules exhibit larger
      dipole moment in the excited state than in the ground state, which in turn
      implies that a potential intramolecular charge transfer (ICT) occurs after
      excitation.

PMID- 21184260
TI  - Going through the rites of passage: timing and transition of menarche, childhood
      sexual abuse, and anxiety symptoms in girls.
AB  - Menarche is a discrete, transitional event that holds considerable personal,
      social, biological, and developmental significance. The present longitudinal
      study examined both the transition and timing of menarche on the trajectory of
      anxiety in girls with histories of childhood maltreatment (N = 93; 63% European
      American, 14% multiracial, 10% Latino, 9% African American, and 4% Native
      American). We hypothesized that because menarche is a novel, unfamiliar
      experience, girls would show greater anxiety around the time of menarche. The
      anxiety-provoking nature of menarche may be accentuated among earlier-maturing
      girls and girls with histories of childhood sexual abuse. Results indicated that
      earlier-maturing girls were more anxious in the pre- and peri-menarche periods
      than their later-maturing peers; however, their anxiety declined after menarche.
      Childhood sexual abuse was associated with heightened anxiety throughout this
      transition. The developmental significance of the timing and transition of
      menarche in relation to childhood sexual abuse and anxiety is discussed.

PMID- 21184261
TI  - Who is likely to help and hurt? Profiles of African American adolescents with
      prosocial and aggressive behavior.
AB  - Prosocial behavior and aggression among children and adolescents are important
      indicators of social and interpersonal competence. The goal of this study was to
      investigate whether there are different prototypes among African American
      adolescents that can help explain prosocial and aggressive (relational and overt)
      behaviors. Also of interest was whether these profiles differed for boys and
      girls. The selection of independent variables (e.g., empathy, anger management,
      normative beliefs about aggression, and ethnic identity) was guided by an
      information processing model of aggression and prosocial behaviors. The sample
      consisted of 789 (57% female) African American adolescents between the ages of 11
      and 14. Cluster analysis produced three profiles that were similar for boys and
      girls. These were labeled "well-adjusted," "poorly adjusted," and "low identity."
      A fourth profile was labeled "low empathy" for girls and "poor anger management"
      for boys. These four clusters significantly differentiated who engaged in
      prosocial behavior and relational and overt aggression. Findings suggest that
      prevention programs may consider targeting well-adjusted youth to serve as peer
      modes. Additionally, programs that promote empathy, anger management, ethnic
      identity, and normative beliefs against aggression may be useful for reducing
      aggression and increasing prosocial behavior among poorly adjusted youth.

PMID- 21184262
TI  - Physical activity, additional breast cancer events, and mortality among early
      stage breast cancer survivors: findings from the WHEL Study.
AB  - OBJECTIVE: Research suggests that physical activity is associated with improved
      breast cancer survival, yet no studies have examined the association between post
      diagnosis changes in physical activity and breast cancer outcomes. The aim of
      this study was to determine whether baseline activity and 1-year change in
      activity are associated with breast cancer events or mortality. METHODS: A total
      of 2,361 post-treatment breast cancer survivors (Stage I-III) enrolled in a
      randomized controlled trial of dietary change completed physical activity
      measures at baseline and one year. Physical activity variables (total, moderate
      vigorous, and adherence to guidelines) were calculated for each time point.
      Median follow-up was 7.1 years. Outcomes were invasive breast cancer events and
      all-cause mortality. RESULTS: Those who were most active at baseline had a 53%
      lower mortality risk compared to the least active women (HR = 0.47; 95% CI: 0.26,
      0.84; p = .01). Adherence to activity guidelines was associated with a 35% lower
      mortality risk (HR = 0.65, 95% CI: 0.47, 0.91; p < .01). Neither baseline nor 1
      year change in activity was associated with additional breast cancer events.
      CONCLUSIONS: Higher baseline (post-treatment) physical activity was associated
      with improved survival. However, change in activity over the following year was
      not associated with outcomes. These data suggest that long-term physical activity
      levels are important for breast cancer prognosis.

PMID- 21184263
TI  - A review of African American-white differences in risk factors for cancer:
      prostate cancer.
AB  - OBJECTIVE: African American men have higher prostate cancer incidence rates than
      White men, for reasons not completely understood. This review summarizes the
      existing literature of race-specific associations between risk factors and
      prostate cancer in order to examine whether associations differ. METHODS: We
      reviewed epidemiologic studies published between January 1970 and December 2008
      that reported race-specific effect estimates. We focused mainly on modifiable
      risk factors related to lifestyle and health. A total of 37 articles from 21
      study populations met our inclusion criteria. RESULTS: We found no evidence of
      racial differences in associations between prostate cancer and alcohol intake,
      tobacco use, and family history of prostate cancer. Research suggests that a
      modest positive association may exist between height and prostate cancer risk
      (all prostate cancer and advanced prostate cancer) among Whites only. No clear
      patterns were observed for associations with physical activity, weight/body mass
      index, dietary factors, occupational history, sexual behavior, sexually
      transmissible infections, and other health conditions. DISCUSSION: Our results
      suggest few differences in prostate cancer risk factors exist between racial
      groups and underscore areas where additional research is needed. Future studies
      should enroll higher numbers of African American participants and report results
      for advanced prostate cancer.

PMID- 21184264
TI  - Bladder cancer mortality trends and patterns in Cordoba, Argentina (1986-2006).
AB  - BACKGROUND: Bladder cancer is common worldwide and the fourth most commonly
      diagnosed malignancy in men in Argentina. OBJECTIVE: To describe bladder cancer
      mortality trends in Cordoba (1986-2006), considering the effect of age, period,
      and cohort, and to estimate the effect of arsenic exposure on bladder cancer, and
      its interaction with sex, while controlling by smoking habits and space and time
      variation of the rates. METHODS: A joinpoint regression was performed to compute
      the estimated annual percentage changes (EAPC) of the age-standardized mortality
      rates (ASMR) in an adult population from Cordoba, Argentina. A Poisson model was
      fitted to estimate the effect of age, period, and cohort. The influence of
      gender, tobacco smoking (using lung cancer ASMR as surrogate), and arsenic in
      drinking water was examined using a hierarchical model. RESULTS: A favorable
      trend (1986-2006) in bladder cancer ASMR in both sexes was found: EAPC of -2.54
      in men and -1.69 in women. There was a decreasing trend in relative risk (RR) for
      cohorts born in 1931 or after. The multilevel model showed an increasing risk for
      each increase in lung cancer ASMR unit (RR = 1.001) and a biological interaction
      between sex and arsenic exposure. RR was higher among men exposed to increasing
      As-exposure categories (RR male low exposure 3.14, RR male intermediate exposure
      4.03, RR male high exposure 4.71 versus female low exposure). A non-random space
      time distribution of the rates was observed. CONCLUSIONS: There has been a
      decreasing trend in ASMR for bladder cancer in Cordoba. This study confirms that
      bladder cancer is associated with age, gender, smoking habit, and exposure to
      arsenic. Moreover, an effect measure modification between exposure to arsenic and
      sex was found.

PMID- 21184265
TI  - Reproductive history and risk of three breast cancer subtypes defined by three
      biomarkers.
AB  - Breast cancer subtypes defined by estrogen receptor (ER), progesterone receptor
      (PR), and HER2 expression are biologically distinct and thus, may have distinct
      etiologies. In particular, it is plausible that risk factors operating through
      hormonal mechanisms are differentially related to risk of such tumor subtypes.
      Using data from the Breast Cancer Surveillance Consortium, we explored
      associations between reproductive history and three breast cancer subtypes. Data
      on parity and age at first birth were collected from 743,623 women, 10,896 of
      whom were subsequently diagnosed with breast cancer. Cases were classified into
      three subtypes based on tumor maker expression: (1) ER positive (ER+, N = 8,203),
      (2) ER negative/PR negative/HER2 positive (ER-/PR-/HER2+, N = 288), or (3) ER-,
      PR-, and HER2-negative (triple-negative, N = 645). Associations with reproductive
      history, evaluated using Cox regression, differed significantly across tumor
      subtypes. Nulliparity was most strongly associated with risk of ER+ breast cancer
      [hazard ratio (HR) = 1.31, 95% confidence interval (CI): 1.23-1.39]; late age at
      first birth was most strongly associated with risk of ER-/PR-/HER2+ disease (HR =
      1.83, 95% CI: 1.31-2.56). Neither parity nor age at first birth was associated
      with triple-negative breast cancer. In contrast to ER+ and ER-/PR-/HER2+
      subtypes, reproductive history does not appear to be a risk factor for triple
      negative breast cancer.

PMID- 21184266
TI  - Helicobacter pylori infection and gastric cardia cancer: systematic review and
      meta-analysis.
AB  - OBJECTIVE: Helicobacter pylori infection is the most important risk factor for
      gastric cancer, but no association with cardia cancer has been recognized.
      However, a heterogeneous distribution of etiologically distinct types of cardia
      cancer may contribute to explain conflicting findings between studies in high-
      and low-risk settings. We aimed to quantify the association between H. pylori
      infection and gastric cardia cancer through meta-analysis, and to provide an
      explanation for the expected heterogeneity of results. METHODS: We systematically
      reviewed published studies addressing the association between H. pylori infection
      and gastric cardia cancer (up to June 2009), and extracted relative risk (RR)
      estimates for the association with cardia and non-cardia cancers. Summary RR
      estimates and 95% confidence intervals (95% CI) were computed using random
      effects models. Subgroup analyses were conducted, namely according to gastric
      cancer risk settings. RESULTS: Thirty-four articles were considered for meta
      analysis. For cardia cancer, summary RR was 1.08 (95% CI 0.83-1.40; I (2) =
      52.8%), higher in high-risk (RR = 1.98; 95% CI 1.38-2.83; I (2) = 18.4%) than in
      low-risk settings (RR = 0.78; 95% CI 0.63-0.97; I (2) = 11.6%). For non-cardia
      cancer, RR estimates were similar in high- (RR = 3.02; 95% CI 1.92-4.74; I (2) =
      90.7%) and low-risk settings (RR = 2.56; 95% CI 1.99-3.29; I (2) = 46.6%). These
      observations were consistent across different inclusion criteria and when
      accounting for the virulence of the infecting strains. CONCLUSIONS: In high-risk
      settings, a positive association between H. pylori infection and gastric cancer
      was observed both for cardia and non-cardia cancers. The results support the
      hypothesis of a heterogeneous distribution of etiologically distinct types of
      cardia cancer.

PMID- 21184267
TI  - A Promotora-administered group education intervention to promote breast and
      cervical cancer screening in a rural community along the U.S.-Mexico border: a
      randomized controlled trial.
AB  - BACKGROUND: Breast cancer is the most common neoplasm among Hispanic women.
      Cervical cancer has a higher incidence and mortality among Hispanic women
      compared with non-Hispanic White women. OBJECTIVE: To assess the effectiveness of
      a promotora-administered educational intervention to promote breast and cervical
      cancer screening among post-reproductive age, medically underserved Hispanic
      women residing along the U.S.-Mexico border. METHODS: Women age 50 or older were
      eligible to participate in this intervention study. A total of 381 subjects
      agreed to participate. Women were randomly assigned into one of two groups,
      educational intervention or usual care. The primary outcomes were self-reported
      mammogram and Pap smear screening. Logistic regression analysis was used to
      compute odds ratios for comparisons between intervention and control groups.
      RESULTS: Women in the intervention group were 2.0 times more likely to report
      having had a mammogram within the last year when compared with the usual care
      group (95% CI = 1.3-3.1). Likewise, women in the intervention group were 1.5
      times more likely to report having a Pap smear within the last year when compared
      with the usual care group, although this was not statistically significant (95%
      CI = 0.9-2.6). In a secondary analysis, the intervention suggests a stronger
      effect on those that had not had a mammogram or Pap smear within the past year at
      baseline. CONCLUSIONS: A promotora-based educational intervention can be used to
      increase breast and cervical cancer screening utilization among Hispanic women.

PMID- 21184268
TI  - Phosphorylated S6K1 is a possible marker for endocrine therapy resistance in
      hormone receptor-positive breast cancer.
AB  - Cross-talk between the estrogen receptor and the mammalian target of rapamycin
      (mTOR) pathway is one of the mechanisms of endocrine therapy resistance, and the
      phosphorylated S6 kinase 1(p-S6K1) is known to be a marker of the mTOR pathway
      activation. The authors assessed the prognostic significance of p-S6K1 according
      to the hormone receptor (HR) status. The expression of p-S6K1 was evaluated in
      304 breast cancer tissues, and the association between its expression and patient
      outcomes was investigated. Among 197 cases with the HR (+) tumor, 70 (35.5%) were
      positive for p-S6K1. Most of the patients (97.5%) with the HR (+) tumor received
      adjuvant endocrine therapy. The expression of p-S6K1 was found to be an
      independent worse prognosticator affecting overall survival (OS) and breast
      cancer-specific survival (BCSS) in the HR (+) group (hazard ratio, 2.62; 95%
      confidence interval [CI], 1.19-5.76; P = 0.017 and hazard ratio, 3.25; 95% CI,
      1.20-8.82; P = 0.020, respectively). In the HR (-) group, however, the p-S6K1
      expression was not associated with patients' survival. The expression of p-S6K1
      is a worse prognostic factor in patients with HR (+) tumors. These results
      suggest that the p-S6K1 expression might be a marker for endocrine therapy
      resistance in patients with HR (+) tumors.

PMID- 21184270
TI  - Chemotherapy for metastatic breast cancer. Comparison of clinical practice and
      cost of drugs in two cohorts of patients: 1994-1998 and 2003-2006.
AB  - Although new chemotherapeutic drugs for metastatic breast cancer (MBC) have been
      approved over the past decade, it is unclear whether this has changed the overall
      outcome of patients. This study assessed the clinical and economic impacts of
      these drugs. We retrospectively studied MBC patients receiving chemotherapy in
      our institution over two time periods, 1994-1998 and 2003-2006. Patient
      characteristics and outcomes, and treatment characteristics and costs (?, 2008)
      were compared. Three hundred and one patients were identified, 149 patients in
      the first cohort and 152 in second one. The median number of lines of
      chemotherapy was similar in the two cohorts (three lines). The median costs of
      chemotherapy per patient nearly doubled over time, from 6,272 ? in the 1994-1998
      cohort to 13,035 ? in the 2003-2006 cohort (P < 0.001). No survival difference
      was observed between the two groups, with a 3-year survival rate estimated to 41%
      in the 1994-1998 cohort and 44% in the 2003-2006 cohort (P = 0.52). In
      multivariate analysis, prognostic factors associated with longer overall survival
      were single metastatic site (HR 0.48; P < 10-3), bone metastases (HR = 0.67; P =
      0.007) and positive hormone receptors (HR 0.56; P = 0.0002). New chemotherapeutic
      agents induced a significant cost increase over time. The limited size and
      heterogeneity of our cohort do not allow any conclusion concerning their impact
      on survival.

PMID- 21184269
TI  - Significance of ER-Src axis in hormonal therapy resistance.
AB  - The estrogen receptor (ER) is implicated in the progression of breast cancer.
      Despite positive effects of hormonal therapy, initial or acquired resistance to
      endocrine therapies frequently occurs. Recent studies suggested ERalpha
      coregulator PELP1 and growth factor receptor ErbB2/HER2 play an essential role in
      hormonal therapy responsiveness. Src axis couples ERalpha with HER2 and PELP1,
      thus representing a new pathway for targeted therapy resistance. To establish the
      significance of ER-Src axis in PELP1 and HER2 mediated therapy resistance, we
      have generated model cells that stably express Src-shRNA under conditions of
      PELP1, HER2 deregulation. Depletion of Src using shRNA substantially reduced E2
      mediated activation of Src and MAPK activation in resistant model cells.
      Pharmacological inhibition of Src using dasatinib, an orally available inhibitor
      substantially inhibited the growth of therapy resistant MCF7-PELP1, MCF7-HER2,
      and MCF7-Tam model cells in proliferation assays. In post-menopausal xenograft
      based studies, treatment with dasatinib significantly inhibited the growth of
      therapy resistant cells. IHC analysis revealed that the tumors were ERalpha
      positive, and dasatinib treated tumors exhibited alterations in Src and MAPK
      signaling pathways. Combinatorial therapy of tamoxifen with dasatinib showed
      better therapeutic effect compared to single agent therapy on the growth of
      therapy resistant PELP1 driven tumors. The results from our study showed that ER
      Src axis play an important role in promoting hormonal resistance by proto
      oncogenes such as HER2, PELP1, and blocking this axis prevents the development of
      hormonal independence in vivo. Since PELP1, HER2, and Src kinase are commonly
      deregulated in breast cancers, combination therapies using both endocrine agents
      and dasatinib may have better therapeutic effect by delaying the development of
      hormonal resistance.

PMID- 21184271
TI  - CG0006, a novel histone deacetylase inhibitor, induces breast cancer cell death
      via histone-acetylation and chaperone-disrupting pathways independent of ER
      status.
AB  - We previously reported that CG0006, a novel hydroxamate-based pan-histone
      deacetylase inhibitor (HDACI), suppresses the growth of human cancer cells. Here,
      we tested the ability of CG0006 to inhibit breast cancer cell proliferation in
      relation to estrogen receptor (ER) status, and examined changes in the expression
      of cell-cycle regulatory proteins. CG0006 effects on the proliferation of
      multiple human cancer cell lines were tested using MTT and MTS assays. Changes in
      estrogen-signaling proteins and cell-cycle regulatory proteins were examined by
      western blotting and quantitative RT-PCR, and cell-cycle effects were tested
      using flow cytometry. CG0006 increased histone H3 and H4 acetylation, up
      regulated p21 protein, and promoted cell-cycle arrest, inducing G(2)/M-phase
      accumulation in ER-positive MCF7 cells, and G(1)- and G(2)/M-phase accumulation
      in ER-negative MDA-MB-231 cells. In both cell types, CG0006 treatment (1 MUM)
      reduced the levels of the estrogen-signaling proteins ERalpha and cyclin D1, and
      promoted massive degradation of cell-cycle regulatory proteins. CG0006 down
      regulated the histone deacetylase HDAC6 at the protein level in association with
      a subsequent increase in Hsp90 and alpha-tubulin acetylation. HDAC6 depletion
      using small interfering RNA produced a protein-degradation phenotype similar to
      that of CG0006 treatment. These findings suggest that CG0006 inhibits breast
      cancer cell growth by two different pathways: a histone acetylation-dependent
      pathway, and a non-epigenetic pathway that disrupts chaperone function.

PMID- 21184272
TI  - Evaluation of estrogen and progesterone receptors in non-neoplastic breast tissue
      of women of reproductive age exposed to tamoxifen and raloxifene: a randomized,
      double-blind study.
AB  - The objective of the present study was to compare the effects of tamoxifen and
      raloxifene in non-neoplastic breast epithelium. A randomized, double-blind study
      was carried out in 57 ovulatory, premenopausal women of 18-40 years of age, who
      had been diagnosed with fibroadenoma of the breast. The patients were divided
      into three groups: Group A: placebo, n=20; Group B: tamoxifen 20 mg/day, n = 21;
      and Group C: raloxifene 60mg/day, n=16. The study medication was given for 22
      days starting on the first day of the menstrual cycle. On the 23rd day, the
      fibroadenoma was removed and a sample of non-neoplastic breast tissue was
      collected for immunohistochemical evaluation of estrogen and progesterone
      receptors. Comparison between the mean percentages of stained nuclei in the three
      groups was performed by analysis of variance and multiple comparisons, using
      Tukey's method to compare pairwise means, with significance established at P <
      0.05. Exposition to tamoxifen or raloxifene resulted in a significant and similar
      reduction in the mean percentage of stained nuclei for estrogen and progesterone
      receptors (P<0.0001). Tamoxifen and raloxifene reduce progesterone and estrogen
      receptor alpha expression significantly and to a similar extent in the non
      neoplastic breast tissue of women of reproductive age.

PMID- 21184273
TI  - Does radiotherapy planning without breath control compensate intra-fraction heart
      and its compartments' movement?
AB  - This prospective study investigated radiation dose and volume changes during
      breathing cycle. Ten patients with left breast carcinoma receiving radiotherapy
      were included. Treatment planning images were obtained as three different sets of
      series taken: without breath control (F), deep inspiration (I), and end of
      expiration (E), with 3-mm intervals. As such, whole breath cycle was simulated.
      CT images taken during I and E were registered to F, according to DICOM
      coordinates. Each patient's target and organ at risk volumes were contoured by
      the primary radiation oncologist except heart components which were contoured by
      radiologist on F, I and E series. Radiotherapy planning was done on F series,
      then planning and beam data were transferred from F to I and E image series.
      Target and organs at risk (OAR) dose distributions for E and I image series were
      obtained. Dose changes between F, E, and I phases for whole heart and components,
      namely, left ventricle (LV), right ventricle (RV), left auricle (LA), right
      auricle (RA), and left anterior descendent artery (LAD) were examined.
      Furthermore, the issue of any compartment representing the maximum heart dose was
      investigated. Volume and dose variations for heart, LV, RV, LA, RA, and LAD were
      observed during breath cycle. Exposured dose was more than defined tolerance
      level for LV, RV, and LAD in some patients. However, dose differences between F-I
      and F-E were not statistically significant. Radiotherapy planning without breath
      control is not capable of compensating for whole intra-fraction heart and its
      components' volumes and dose changes.

PMID- 21184274
TI  - PALB2 germline mutations in familial breast cancer cases with personal and family
      history of pancreatic cancer.

PMID- 21184275
TI  - Investigating Hardy-Weinberg equilibrium in case-control or cohort studies or
      meta-analysis.
AB  - Yu et al. (Breast Cancer Res Treat 117:675-677, 2009) recently stated that
      testing for deviation from Hardy-Weinberg equilibrium (HWE) is necessary to
      identify systematic genotyping errors in case-control studies. They criticized a
      meta-analytic study for the deviation from HWE in the case group of one study.
      The aim of this article is twofold. First, we derive recommendations on how to
      test for deviations from HWE in different study designs. Second, we develop a
      meta-analytic framework for assessing compatibility with HWE or measuring
      deviation from HWE. The authors sketch the possible reasons behind deviation from
      HWE and provide guidelines for proper investigation of HWE deviations in
      different study designs. The authors argue that the standard HWE chi2 lack of fit
      test is logically flawed and provide a logically unflawed approach for measuring
      deviation from HWE using confidence intervals. The proposed method is applicable
      to meta-analyses of both case-control or cohort association studies. The proposed
      approach is illustrated using the meta-analysis criticized by Yu et al.
      Heterogeneity between studies can be assessed. The critique of Yu et al. to the
      article of Frank et al. (Breast Cancer Res Treat 111:139-144, 2008) can be
      refuted. Even more, validity of HWE can be proven for the pooled control sample.
      The authors advocate the use of a confidence interval-based approach to assess
      HWE. The latter should only be investigated in control populations. In
      multicenter studies or meta-analysis, deviation from HWE should be analyzed using
      a meta-analytic approach.

PMID- 21184276
TI  - A BRCA2 mutation incorrectly mapped in the original BRCA2 reference sequence, is
      a common West Danish founder mutation disrupting mRNA splicing.
AB  - Inherited mutations in the tumor suppressor genes BRCA1 and BRCA2 predispose
      carriers to breast and ovarian cancer. The authors have identified a mutation in
      BRCA2, 7845+1G>A (c.7617+1G>A), not previously regarded as deleterious because of
      incorrect mapping of the splice junction in the originally published genomic
      reference sequence. This reference sequence is generally used in many
      laboratories and it maps the mutation 16 base pairs inside intron 15. However,
      according to the recent reference sequences the mutation is located in the
      consensus donor splice sequence. By reverse transcriptase analysis, loss of exon
      15 in the final transcript interrupting the open reading frame was demonstrated.
      Furthermore, the mutation segregates with a cancer phenotype in 18 Danish
      families. By genetic analysis of more than 3,500 Danish breast/ovarian cancer
      risk families, the mutation was identified as the most common BRCA2 mutation in
      West Denmark, while it is rare in Central and East Denmark and not identified in
      South Sweden. Haplotype analysis using dense SNP arrays indicated a common
      founder of the mutation approximately 1,500 years ago.

PMID- 21184277
TI  - Effect of alpha-ketoglutarate on neurobehavioral, neurochemical and oxidative
      changes caused by sub-chronic cyanide poisoning in rats.
AB  - Recent studies revealed that alpha-ketoglutarate (A-KG) alone or with sodium
      thiosulfate (STS) provide significant protection against acute and sub-acute
      cyanide poisoning in rodents. This study addresses the protective effect of A-KG
      and/or STS in sub-chronic (90 days) cyanide poisoning. Wistar rats were divided
      into seven groups (n = 10): Control animals, potassium cyanide (KCN) A-KG, STS,
      KCN + A-KG, KCN + STS and KCN + A-KG + STS. Spontaneous motor activity and motor
      coordination were recorded every 15th day. Lipid peroxidation (LPO), reduced
      glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and
      catalase (CAT) in blood, brain, liver and kidney, and glutamate, aspartate and
      dopamine in discrete regions of brain were measured following 90 days exposure.
      Cyanide significantly decreased motor coordination, accompanied by increase in
      LPO (blood, brain and liver) and dopamine (corpus striatum and cerebral cortex)
      levels, and depletion in GSH (blood, brain and liver), GPx (brain and liver), SOD
      (brain and liver), and CAT (blood and brain) levels. Although treatment of A-KG
      and STS alone significantly blunted the toxicity of KCN, concomitant use of both
      afforded the maximum protection. This study shows a promising role of A-KG and
      STS as treatment regime for long term cyanide exposure.

PMID- 21184278
TI  - Calcium signalling and Alzheimer's disease.
AB  - New insights into how Ca(2+) regulates learning and memory have begun to provide
      clues as to how the amyloid-dependent remodelling of neuronal Ca(2+) signalling
      pathways can disrupt the mechanisms of learning and memory in Alzheimer's disease
      (AD). The calcium hypothesis of AD proposes that activation of the amyloidogenic
      pathway remodels the neuronal Ca(2+) signalling pathways responsible for
      cognition by enhancing the entry of Ca(2+) and/or the release of internal Ca(2+)
      by ryanodine receptors or InsP(3) receptors. The specific proposal is that Ca(2+)
      signalling remodelling results in a persistent elevation in the level of Ca(2+)
      that constantly erases newly acquired memories by enhancing the mechanism of long
      term depression (LTD). Neurons can still form memories through the process of
      LTP, but this stored information is rapidly removed by the persistent activation
      of LTD. Further dysregulation in Ca(2+) signalling will then go on to induce the
      neurodegeneration that characterizes the later stages of dementia.

PMID- 21184280
TI  - The dynamics of devaluation: the spiritual disease of civilization.
AB  - The presentation seeks to identify a major spiritual sickness that is not only
      widespread but also kept out of public discourse or seriously minimized in terms
      of its scope and destructive effects. Most religious traditions derive much of
      their power by giving 'believers' a sense of personal and/or collective worth,
      where worth may be associated with a feeling of positive valuation. However, as
      religious traditions decline in the wake of a materialist science or as they
      become corrupted by developing false forms of valuation, Western, if not world,
      civilization becomes ever more threatened by the disease of devaluation. In this
      context, the study will attempt three things: (1) to identify the manifestations
      or symptoms of devaluation as a disease of the soul; (2) to place these symptoms
      in a kind of historical context; and (3) to develop some effective healing
      strategies that may serve to counter, not only the symptoms but also the root
      causes of the disease of devaluation. In particular, it will be argued that false
      forms of valuation need to be identified so that public discourse can minimize
      the possibilities of these taking root and leading to one of the tragedies of our
      time: that is, the gaining of a kind of substitute value by the devaluing of some
      other group.

PMID- 21184279
TI  - Chronic variable stress alters inflammatory and cholinergic parameters in
      hippocampus of rats.
AB  - In the present study we investigated the effect of chronic variable stress (CVS)
      on some parameters of the immune system, including levels of cytokines
      [interleukin 1beta (IL-1 beta), interleukin 6 (IL-6), tumor necrosis factor alpha
      (TNF- alpha)] and chemokine CCL2 (MCP-1) in the hippocampus of rats.
      Acetylcholinesterase activity was also evaluated. Sixty-day old Wistar rats were
      submitted to different mild stressors for 40 days. After the last stress section,
      the cytokines and MCP-1 were determined by immunoassay and acetylcholinesterase
      activity by colorimetric method. Results showed that chronic stress significantly
      increased the levels of IL-1beta, IL-6 and TNF-alpha, but did not alter the
      levels of MCP-1. In addition, acetylcholinesterase activity was increased in the
      hippocampus of rats subjected to CVS. These findings suggest that inflammation
      and cholinergic dysfunction may be, at least in part, important contributors to
      the neurological dysfunction observed in some depressed patients.

PMID- 21184281
TI  - The prevalence of spirituality, optimism, depression, and fatalism in a bi-ethnic
      stroke population.
AB  - To provide insight into the reduced post-stroke all-cause mortality among Mexican
      Americans, we explored ethnic differences in the pre-stroke prevalence of (1)
      spirituality, (2) optimism, (3) depression, and (4) fatalism in a Mexican
      American and non-Hispanic white stroke population. The Brain Attack Surveillance
      in Corpus Christi (BASIC) project is a population-based stroke surveillance study
      in Nueces County, Texas. Seven hundred ten stroke patients were queried. For
      fatalism, optimism, and depression scales, unadjusted ethnic comparisons were
      made using linear regression models. Regression models were also used to explore
      how age and gender modify the ethnic associations after adjustment for education.
      For the categorical spirituality variables, ethnic comparisons were made using
      Fisher's exact tests. Mexican Americans reported significantly more spirituality
      than non-Hispanic whites. Among women, age modified the ethnic associations with
      pre-stroke depression and fatalism but not optimism. Mexican American women had
      more optimism than non-Hispanic white women. With age, Mexican American women had
      less depression and fatalism, while non-Hispanic white women had more fatalism
      and similar depression. Among men, after adjustment for education and age, there
      was no ethnic association with fatalism, depression, and optimism. Spirituality
      requires further study as a potential mediator of increased survival following
      stroke among Mexican Americans. Among women, evaluation of the role of optimism,
      depression, and fatalism as they relate to ethnic differences in post-stroke
      mortality should be explored.

PMID- 21184282
TI  - Defining and exploring modesty in Jewish American women.
AB  - Whether culture-based modesty may be a barrier to women's health care has been a
      longstanding question. Numerous studies have noted that, in certain cultures,
      modesty is considered a barrier to mammography screening and breast feeding.
      Though modesty has been noted as an inherent aspect of the lived experience of
      many cultures, no extant measures or clear definitions were found. Jewish women,
      some having strict rules regarding modesty, were sampled to understand their
      definition of modesty. These perspectives were objectively analyzed using Q
      methodology. We found that although some perspectives on modesty may be accounted
      for by culture, there are others that are not.

PMID- 21184283
TI  - An ethic of resistance: choosing life in health messages for African American
      women.
AB  - Media messages directed to African American women are more likely to have health
      content that emphasizes negative outcomes or sexual stereotypes. This paper
      critiques the use of health messages that focus on high mortality and morbidity
      rates, yet have not reduced health disparities, but have instead reduced Black
      women's bodies to carriers of disease. I introduce an ethic of resistance that
      privileges the authority and wholeness of Black women rather than disease and
      fragmentation. An ethic of resistance helps Black women connect to their
      spiritual health, move from passive receiver to active resister of negative
      messages, and break the generational silence to demystify sexuality and integrate
      it into a lifestyle of wholeness. My hope is to improve the health outcomes of
      African American women by improving the message.

PMID- 21184284
TI  - A new frameshift MEN1 gene mutation associated with familial malignant
      insulinomas.
AB  - MEN-1 is an autosomal dominant familial cancer syndrome characterized by
      involvement of parathyroid, enteropancreatic endocrine tissues and the anterior
      pituitary gland. Malignant insulinomas are rare, and therefore, there are few
      data regarding their clinical presentation and long-term prognosis. In this
      report we present a large family with malignant insulinoma and
      hyperparathyroidism with MEN-1 gene mutation analysis. A large family (three
      generations) with several members affected were evaluated for clinical and
      biochemical characteristic of MEN-1 syndrome. Genetic analysis for MEN1 gene was
      carried out in all family members using PCR amplification of coding regions
      followed by direct sequencing. In three brothers that presented with
      hypoglycemia, insulinoma was confirmed and two were malignant according to
      pathology and surgery report. Two of them had hyperparathyroidism too. Mutation
      screening revealed the presence of a two nucleotide deletion in the exon 2
      (c199_200del2). In the current study, the deletion happens early in the sequence,
      and obviously results in a non-functional gene product. However, it will be
      helpful to further examine somatic mutations and other genetic markers for a more
      precise study of genotype-phenotype correlation.

PMID- 21184285
TI  - Familial gastric cancer: update for practice management.
AB  - About 90% of gastric carcinoma presents a sporadic setting and only 10% shows a
      familial cluster; among this group, 1-3% are considered as hereditary syndromes,
      with a clear genetic pathway. The most important genetic mechanisms are
      associated with CDH1 germline mutations, causing the hereditary diffuse gastric
      cancer syndrome. Other inherited predispositions with gastric carcinoma are the
      hereditary nonpolyposis colorectal cancer, Li-Fraumeni and Peutz-Jeghers
      syndromes. In this brief update, we described these principal hereditary
      syndromes offering a simple management to physicians where are these diseases
      diagnosed.

PMID- 21184286
TI  - Public managed care and service access in outpatient substance abuse treatment
      units.
AB  - The continued growth of public managed behavioral health care has raised concerns
      about possible effects on services provided. This study uses a national sample of
      outpatient substance abuse treatment units surveyed in 2005 to examine
      associations between public managed care and service access, measured as both the
      types of services provided and the amount of treatment received by clients. The
      percentage of clients funded through public managed care versus other types of
      public funding was positively associated with treatment units' odds of providing
      some types of resource-intensive services and with the odds of providing
      transportation to clients, but was negatively associated with the average number
      of individual therapy sessions clients received over the course of treatment. In
      general, public managed care does not appear to restrict access to outpatient
      substance abuse treatment, although states should monitor these contracts to
      ensure clients receive adequate courses of individual treatment.

PMID- 21184288
TI  - The structure and function of endophilin proteins.
AB  - Members of the BAR domain protein superfamily are essential elements of cellular
      traffic. Endophilins are among the best studied BAR domain proteins. They have a
      prominent function in synaptic vesicle endocytosis (SVE), receptor trafficking
      and apoptosis, and in other processes that require remodeling of the membrane
      structure. Here, we discuss the role of endophilins in these processes and
      summarize novel insights into the molecular aspects of endophilin function. Also,
      we discuss phosphorylation of endophilins and how this and other mechanisms may
      contribute to disease.

PMID- 21184287
TI  - Examination of the utility of psychotherapy for patients with treatment resistant
      depression: a systematic review.
AB  - OBJECTIVE: To examine the utility of psychotherapy in managing treatment
      resistant depression. DATA SOURCES: PubMed, PsycInfo, Embase, Cochrane Registry
      of Controlled Clinical Trials, article bibliographies. REVIEW METHODS: Eligible
      articles had to be in English and include English-speaking adult outpatients from
      general medical or mental health clinics. Studies had to be randomized clinical
      trials (RCT) involving at least one of the following psychotherapy modalities:
      cognitive therapy, interpersonal therapy, or behavior therapy. Patients were
      considered treatment resistant if they reported partial or no remission following
      treatment with an adequate antidepressant dose for >= 6 weeks. Exclusion criteria
      included receiving psychotherapy at the time of recruitment, and/or comorbid
      psychiatric conditions unlikely to be treated outside of specialized mental
      health care (e.g., severe substance abuse). Due to heterogeneity in study
      designs, a summary estimate of effect was not calculated. Studies were critically
      analyzed and a qualitative synthesis was conducted. RESULTS: Of 941 original
      titles, 13 articles evaluating 7 unique treatment comparisons were included.
      Psychotherapy was examined as an augmentation to antidepressants in five studies
      and as substitution treatment in two studies. A total of 592 patients were
      evaluated (Mean age ~40 y; Females = 50-85%; Caucasians >= 75%). The STAR*D trial
      used an equipoise stratified randomization design; the remaining studies were
      RCTs. Compared to active management, two good quality trials showed similar
      benefit from augmenting antidepressants with psychotherapy; one fair quality and
      one poor quality trial showed benefit from psychotherapy augmentation; and one
      good and one poor trial found similar benefit from substituting psychotherapy for
      antidepressants. One fair quality trial showed lithium augmentation to be more
      beneficial than psychotherapy. CONCLUSIONS: Review demonstrates the utility of
      psychotherapy in managing treatment resistant depression. However, evidence is
      sparse and results are mixed. Given that quality trials are lacking, rigorous
      clinical trials are recommended to guide practice. In the interim, primary care
      providers should consider psychotherapy when treating patients with treatment
      resistant depression.

PMID- 21184289
TI  - Red blood cell production from immortalized progenitor cell line.
AB  - The supply of transfusable red blood cells (RBCs) is not sufficient in many
      countries. If immortalized erythroid progenitor cell lines able to produce
      transfusable RBCs in vitro were established, they would be valuable resources.
      However, such cell lines have not been established. We have developed a robust
      method to establish immortalized erythroid progenitor cell lines following the
      induction of hematopoietic differentiation of mouse embryonic stem (ES) cells and
      have established many immortalized erythroid progenitor cell lines so far.
      Although their precise characteristics varied among cell lines, each of these
      lines could differentiate in vitro into more mature erythroid cells, including
      enucleated RBCs. Following transplantation of these erythroid cells into mice
      suffering from acute anemia, the cells proliferated transiently, subsequently
      differentiated into functional RBCs, and significantly ameliorated the acute
      anemia. Considering the number of human ES cell lines that have been established
      so far and the number of induced pluripotent stem cell lines that will be
      established in future, the intensive testing of a number of these lines for
      establishing immortalized erythroid progenitor cell lines may allow the
      establishment of such cell lines similar to the mouse erythroid progenitor cell
      lines.

PMID- 21184290
TI  - Concurrent development of "Burkitt-like" lymphoma and BCL-2-rearranged low-grade
      B cell lymphoma sharing the same germinal center origin.
AB  - B cell lymphoma, unclassifiable, with features intermediate between diffuse large
      B cell lymphoma and Burkitt lymphoma (BL) is a new entity in WHO classification
      2008, and includes Burkitt-like transformation of follicular lymphoma (FL).
      However, the pathological significance of BCL-2/IgH translocation, which is
      characteristic in FL, in newly diagnosed cases of this disease is not well
      understood. We report a patient who developed B cell lymphoma with BL-like
      morphology on the shoulder, whose bone marrow was involved with FL-like cells. BL
      like tumor cells harbored amplified c-MYC genes with BCL-2/IgH translocation, but
      FL-like cells solely had BCL-2/IgH translocation. The sequence analysis of the
      IgH gene revealed both of cells originated from the same clone, showing that the
      aggressive BL-like tumor originated from the FL-like clones simultaneously found
      in the bone marrow. This case suggests that the IgH/BCL-2 translocation found in
      newly diagnosed Burkitt-like lymphoma indicates a history of FL-like indolent
      lymphoma, even if such history is not documented.

PMID- 21184291
TI  - Dopamine D2 occupancy as a biomarker for antipsychotics: quantifying the
      relationship with efficacy and extrapyramidal symptoms.
AB  - For currently available antipsychotic drugs, blockade of dopamine D(2) receptors
      is a critical component for achieving antipsychotic efficacy, but it is also a
      driving factor in the development of extrapyramidal symptoms (EPS). To inform the
      clinical development of asenapine, generic mathematical models have been
      developed for predicting antipsychotic efficacy and EPS tolerability based on
      D(2) receptor occupancy. Clinical data on pharmacokinetics, D(2) receptor
      occupancy, efficacy, and EPS for several antipsychotics were collected from the
      public domain. Asenapine data were obtained from in-house trials. D(2) receptor
      occupancy data were restricted to published positron emission tomography studies
      that included blood sampling for pharmacokinetics. Clinical efficacy data were
      restricted to group mean endpoint data from short-term placebo-controlled trials,
      whereas EPS evaluation also included some non-placebo-controlled trials. A
      generally applicable model connecting antipsychotic dose, pharmacokinetics, D(2)
      receptor occupancy, Positive and Negative Syndrome Scale (PANSS) response, and
      effect on Simpson-Angus Scale (SAS) was then developed. The empirical models
      describing the D(2)-PANSS and D(2)-SAS relationships were used successfully to
      aid dose selection for asenapine phase II and III trials. A broader use can be
      envisaged as a dose selection tool for new antipsychotics with D(2) antagonist
      properties in the treatment of schizophrenia.

PMID- 21184292
TI  - [HIV seroprevalence among STD patients in Nouakchott and Nouadhibou
      (Mauritania)].
AB  - This work presents the results of the behavioural and serologic survey on
      HIV/AIDS conducted from December 2007 to December 2008 among the group of STD
      (sexually transmitted disease) patients, supposed to be at HIV infection risk. In
      Mauritania, the last survey of HIV seroprevalence among the STD patients goes up
      to the year 1995 (the prevalence was estimated then to be 0.9%). The goal was to
      determine the seroprevalence of HIV and syphilis and to gather information on the
      knowledge, the sexual behaviours on a risk concerning the HIV/AIDS, and the
      sexually transmitted disease among these patients. The census has been made on
      over 224 STD patients during the period of the study, without predominance of sex
      and with a majority of young adults. The prevalence for HIV is 9% and for the
      syphilis it is 10%. Actually, the condom is widely underused by this group, even
      in occasional intercourse. The STD patients are a group of risk towards HIV,
      because of their risk behaviours and low level of knowledge.

PMID- 21184293
TI  - [Assessment of the risk of introduction to Tunisia of the Rift Valley fever virus
      by the mosquito Culex pipiens].
AB  - The mosquito Culex pipiens has been involved as vector of the West Nile virus in
      Tunisia. Its bio-ecological characteristics in combination with some
      environmental factors have favoured the emergence of this virus in a West-Nile
      free zone. This leads to question about the potential risk of introducing another
      arbovirus, the Rift Valley fever (RVF) virus, in Tunisia from neighbouring
      countries where RVF circulates. In this study, we have evaluated the vector
      competence of different populations of Cx. pipiens towards two strains of RVF
      virus, the virulent ZH548 and the avirulent Clone 13 by experimental infections
      and the genetic differentiation of these populations of Cx. pipiens using four
      microsatellite loci. We found disseminated infection rates ranging from 0% to
      14.7% and a high genetic differentiation among populations without any
      geographical pattern (no isolation by distance). Thus, although Cx. pipiens is
      able to sustain an amplification of RVF virus, viral dissemination through
      mosquito dispersal would be unlikely. However, as RVF is an emerging disease
      transmitted by several other potential mosquito species (e.g. Ochlerotatus
      caspius), attention should be maintained to survey livestock and mosquitoes in
      Tunisia.

PMID- 21184294
TI  - Reversible NO-catalyzed destruction of the Fe-S cluster of the FNR[4Fe-4S]2+
      transcription factor: a way to regulate the aidB gene activity in Escherichia
      coli cells cultured under anaerobic conditions.

PMID- 21184295
TI  - Alteration of catalysis of CYP74C subfamily enzymes as a result of site-directed
      mutagenesis.

PMID- 21184296
TI  - Microfluidic module for automated isolation and purification of nucleic acids
      from biological samples.

PMID- 21184297
TI  - A pseudovirus system for the testing of antiviral activity of compounds in
      different cell lines.

PMID- 21184298
TI  - The role of social factors in the regulation of stability of the cell genetic
      machinery in animals.

PMID- 21184299
TI  - Photochromism of visual pigment rhodopsin on the femtosecond time scale: coherent
      control of retinal chromophore isomerization.

PMID- 21184300
TI  - Effect of ubiquitination on peptidase activities of proteasomes in genotoxic
      stress.

PMID- 21184301
TI  - Effect of electromagnetic radiation of extremely high frequencies on the fatty
      acid composition of mouse thymic cells in normal state and in systemic
      inflammation.

PMID- 21184302
TI  - Exogenous heat shock protein HSP70 suppresses bacterial pathogen-induced
      activation of human neutrophils.

PMID- 21184303
TI  - Altered transcription and replication are the mechanisms of cytotoxicity of
      antitumor antibiotic olivomycin A.

PMID- 21184304
TI  - Energy-dependent respiration of Bacillus subtilis coupled membranes. A kinetic
      model.

PMID- 21184305
TI  - Orthologs of meiotic proteins in prokaryotic proteomes.

PMID- 21184306
TI  - The effect of propranolol on LPS-induced activation of human neutrophils.

PMID- 21184308
TI  - Molecular analysis of RNA induced by enhancer in Drosophila cells carrying
      reporter genetic constructs.

PMID- 21184307
TI  - Studies of complex formation of olivomycin A and its derivatives with DNA.

PMID- 21184309
TI  - ELISA detection of hazelnut proteins: effect of protein glycation in the presence
      or absence of wheat proteins.
AB  - Hazelnuts are widely used in the food industry, especially confectionary foods.
      Nevertheless, these nuts contain several allergenic proteins that may be
      unexpectedly present as contaminants in various foods and may pose a serious
      threat to allergic consumers. The enzyme-linked immunosorbent assay (ELISA) is
      the preferred method to assess the level of hazelnut protein contamination. It is
      commonly used by both the food industry and enforcement agencies. Several ELISA
      kits are commercially available. However, protein detectability by ELISA may be
      affected by severe changes that proteins undergo during processing. The aim of
      this study is therefore to investigate the impact of processing on the ability to
      detect hazelnut protein by four commercial ELISA kits. Hazelnut proteins in the
      presence or absence of soluble wheat proteins were modified with glucose via the
      Maillard reaction. Changes in hazelnut proteins, such as the formation of protein
      bound carbonyls, losses of reactive lysine residues and free amino groups, and
      severe aggregation dramatically affected the hazelnut protein detection by the
      commercial kits. The observed impact was highly dependent on the type of ELISA
      kit used.

PMID- 21184310
TI  - Migration of antimony from PET bottles into beverages: determination of the
      activation energy of diffusion and migration modelling compared with literature
      data.
AB  - Plastics bottles made from polyethylene terephthalate (PET) are increasingly used
      for soft drinks, mineral water, juices and beer. In this study a literature
      review is presented concerning antimony levels found both in PET materials as
      well as in foods and food simulants. On the other hand, 67 PET samples from the
      European bottle market were investigated for their residual antimony
      concentrations. A mean value of 224 +/- 32 mg kg(-1) was found, the median was
      220 mg kg(-1). Diffusion coefficients for antimony in PET bottle materials were
      experimentally determined at different temperature between 105 and 150 degrees C.
      From these data, the activation energy of diffusion for antimony species from the
      PET bottle wall into beverages and food simulants was calculated. The obtained
      value of 189 kJ mol(-1) was found to be in good agreement with published data on
      PET microwave trays (184 kJ mol(-1)). Based on these results, the migration of
      antimony into beverages was predicted by mathematical migration modelling for
      different surface/volume ratios and antimony bottle wall concentrations. The
      results were compared with literature data as well as international legal limits
      and guidelines values for drinking water and the migration limit set from food
      packaging legislation. It was concluded that antimony levels in beverages due to
      migration from PET bottles manufactured according to the state of the art can
      never reach or exceed the European-specific migration limit of 40 microg kg(-1).
      Maximum migration levels caused by room-temperature storage even after 3 years
      will never be essentially higher than 2.5 microg kg(-1) and in any case will be
      below the European limit of 5 microg kg(-1) for drinking water. The results of
      this study confirm that the exposure of the consumer by antimony migration from
      PET bottles into beverages and even into edible oils reaches approximately 1% of
      the current tolerable daily intake (TDI) established by World Health Organisation
      (WHO). Having substantiated such low antimony levels in PET-bottled beverages,
      the often addressed question on oestrogenic effects caused by antimony from PET
      bottles appears to be groundless.

PMID- 21184311
TI  - "D.O. or die": identity negotiation among osteopathic medical students.
AB  - Doctors of osteopathic medicine (D.O.s) have historically faced an uphill battle
      to gain professional legitimacy and credibility in a U.S. medical culture
      dominated by allopathic medicine. Today, struggles surrounding the negotiation of
      a professional osteopathic identity can be found among osteopathic medical
      students who actively debate the merits of a potential change in the D.O.
      designation. This study examines identity construction by analyzing osteopathic
      medical students' accounts of identity that reveal certain ways they negotiate
      their emerging professional selves. By merging current literature on identity
      negotiation from health and organizational communication, we highlight the
      complex relationship between the discursive construction of professional identity
      and the embodied and material consequences of becoming a D.O.

PMID- 21184312
TI  - Shifting the balance: the contemporary narrative of obesity.
AB  - In this essay, I assess the narrative of obesity as articulated in representative
      contemporary mainstream media fare--namely, The Oprah Winfrey Show, The Biggest
      Loser, and Big Medicine. I contend that the emergent narrative of obesity across
      these programs signals a shift from the historically received narrative in light
      of its intersection with the concurrent culturally resonant narratives of
      addiction and self-actualization. In particular, the proposed "problem" and
      "solution" to obesity, both historically attributed to personal responsibility,
      appear to be shifting in favor of cultural explanations that describe obesity as
      symptomatic of and secondary to broader issues related to community,
      emotionality, and agency. This suggests novel cultural understandings, practices,
      and policies regarding the mounting "obesity epidemic."

PMID- 21184313
TI  - 2009-2010 National Health Law Moot Court Competition.

PMID- 21184314
TI  - 2009-2010 National Health Law Moot Court Competition: best brief.

PMID- 21184315
TI  - The Patient Safety and Quality Improvement Act of 2005.

PMID- 21184316
TI  - Physicians and the first amendment.

PMID- 21184317
TI  - The role of communication in the patient-physician relationship.

PMID- 21184318
TI  - Something more to the story.

PMID- 21184319
TI  - Allocation of health care resources at the point of care.

PMID- 21184320
TI  - A matter of fairness.

PMID- 21184323
TI  - Psychological assessment of children in a community mental health clinic.
AB  - Collaborative and Therapeutic Assessment (TA) models (Finn & Tonsager, 1997;
      Fischer, 1985/1994) use psychological tests to answer client-constructed
      assessment questions in an understandable language, to be an intervention in and
      of themselves, and to initiate recommendations related to the referral. This
      article considers the application of Finn's TA model to an urban community
      psychology clinic in Oakland, California, where foster and kinship care, the
      child welfare system, trauma, neglect, and attachment disruptions are children's
      usual experience. These children hide their pain and complaints (Kelly, 1999),
      but show highly problematic behaviors to bewildered and frustrated caretakers,
      social workers, and school personnel. Their trauma, however, also often permeates
      the assessment data and shocks the assessor. A rationale is made for the
      necessity of a relational, culturally aware, systemic model in providing
      psychological assessment services to children and families in a community
      setting.

PMID- 21184324
TI  - Why did she put nail polish in my drink? Applying the Therapeutic Assessment
      model with an African American foster child in a community mental health setting.
AB  - Although the majority of research on Therapeutic Assessment (TA) discusses the
      application of TA in research or private practice settings, we found that the
      model could be applied in a community mental health setting. We argue that when
      implementing this model with racially diverse, low socioeconomic status children,
      it is essential to integrate issues of class, privilege, and race into the
      assessment process. A case is presented that illuminates the specific concerns
      and struggles of adapting this model to a community psychology population. This
      analysis includes the interface with systems, placement stability, and
      consideration of culturally responsible treatment. We also demonstrate how the
      support of a treatment team helps the individual clinician process and integrate
      the levels of trauma and pain with which these families present.

PMID- 21184325
TI  - Training assessors in Therapeutic Assessment.
AB  - This article focuses on the use of the comprehensive Therapeutic Assessment
      training model (Finn, 2007) with a child and his mother. The mother observed the
      child's testing sessions and was actively involved in a family intervention
      session as a way of translating assessment results into practice. One
      psychologist administered the psychological tests with the child, and 2 other
      clinicians worked with the mother throughout the process. We offer ideas about
      learning and training in the context of our case in Therapeutic Assessment. We
      investigate the parallel process between the way in which parents learn about
      their child's perspective and the way in which clinicians learn about the
      family's perspective. We discuss our discoveries in the context of planning case
      interventions. We explore the impact of trauma and ways of holding and containing
      this difficult work within our community and with each other.

PMID- 21184326
TI  - Therapeutic Assessment "on the Front Lines": comment on articles from WestCoast
      Children's Clinic.
AB  - I comment on the articles by Mercer (2011/this issue); Guerrero, Lipkind, and
      Rosenberg (2011/this issue); and Haydel, Mercer, and Rosenblatt (2011/this
      issue), which describe their practice of collaborative and therapeutic
      psychological assessment in a community mental health setting. These articles
      demonstrate that collaborative and Therapeutic Assessment can be used
      successfully with clients from underprivileged, high-risk backgrounds. Such
      assessments are rigorous for both clients and assessors, and their success
      depends on the ability of clinicians to form trusting relationships with clients.
      In fact, empathic disruptions by assessors are almost inevitable during the
      collaborative assessment process, especially if assessors' backgrounds and
      contexts are quite different from those of their clients. However, if assessors
      receive enough support to "take off their white coats" and reach into their
      clients' worlds, such disruptions can be repaired, leading to positive changes in
      both clients and assessors. This kind of assessment work is not for the faint of
      heart, but it is immensely rewarding.

PMID- 21184327
TI  - Reliability and validity of the Spanish version of the Minnesota Multiphasic
      Personality Inventory-Adolescent (MMPI-A).
AB  - The aim of this study was to determine the test-retest reliability and internal
      consistency of the scales of the Spanish version of the Minnesota Multiphasic
      Personality Inventory-Adolescent (MMPI-A; Butcher et al., 1992). Two samples of
      939 and 109 Spanish adolescents ages 14 to 18 years were assessed with the MMPI-A
      in their school environment. The first sample responded to the inventory once,
      whereas the second sample responded to it on 2 occasions with a 2-week interval
      between sessions. Results showed no significant differences in means or variances
      between the first and the second test administration for most MMPI-A scales. Test
      retest reliability ranged between .62 (Amorality, Ma(1)) and .92 (Immaturity,
      IMM); most correlations exceeded .70. Internal consistency values for the MMPI-A
      scales in the pretest and posttest were very similar overall. External validity
      of the MMPI-A was demonstrated through several significant correlations between
      its scales and YSR/11-18 syndromes and social interaction measures. The highest
      correlations were established between the Anxious/Depressed YSR/11-18 scale and
      other MMPI-A scales such as Schizophrenia (Sc), Welsh's Anxiety (A), Adolescent
      Anxiety (A-anx) and Adolescent-Alienation (A-aln), and between the Social
      Avoidance and Distress Scale and the MMPI-A Adolescent-Social Discomfort (A-sod)
      scale.

PMID- 21184328
TI  - Validity of the PAI interpersonal scales for measuring the dimensions of the
      interpersonal circumplex.
AB  - Two studies evaluated the validity of the interpersonal scales, Dominance (DOM)
      and Warmth (WRM), from the Personality Assessment Inventory (PAI; Morey, 1991,
      2007) to measure the 2 dimensions of the interpersonal circumplex (IPC). In Study
      1, 114 college freshmen completed the PAI and the Interpersonal Adjectives Scale
      (IAS; Wiggins, 1995). In Study 2, 170 college students completed the PAI and the
      Inventory of Interpersonal Problems-Short Circumplex (IIP-SC; Soldz, Budman,
      Demby, & Merry, 1995). The results of both studies supported the convergent
      validity of DOM and WRM, although discriminant validity was stronger using the
      IIP-SC as the criterion. Circumplex projections placed DOM and WRM in the
      appropriate segments of both the IAS and IIP-SC. These findings provide
      additional support for the validity of the PAI interpersonal scales as measures
      of the primary dimensions of the IPC.

PMID- 21184329
TI  - Effective cutoffs for detecting random, partially random, and nonrandom 370-item
      MMPI-2 short form protocols.
AB  - The ability of the 370-item short form MMPI-2 (Butcher, Graham, Ben-Porath,
      Tellegen, Dahlstrom, & Kaemmer, 2001) validity scales to detect random protocols
      was investigated using samples of 500 nonrandom protocols, 250 half-random
      protocols, and 250 all-random protocols. The long-form cutoff of VRIN >= 80 was
      unable to detect protocols with either level of randomness. The long-form cutoffs
      of Fp >= 100 or F >= 100 were able to detect all-random but not half-random
      protocols. Alternative cutoffs for VRIN, Fp, and F were investigated and short
      form subscales of those scales were developed to improve detection of partially
      random protocols. An algorithm using alternative cutoffs for the scales and the
      new subscales was highly effective, detecting almost all of the random protocols
      as well as the nonrandom protocols. A follow-up cross-validation study was
      conducted that confirmed the effectiveness of the algorithm.

PMID- 21184330
TI  - Adjective checklist to assess the big five personality factors in the Argentine
      population.
AB  - The aim of this work was to develop an adjective checklist to assess the Big Five
      personality factors in the Argentine population. The new instrument was
      administered to pilot (n= 112), validation (n= 372), and replication (n= 309)
      samples. The final version of the checklist included 67 adjectives encompassing
      its 5 dimensions. Factor analysis results were consistent with the Five-factor
      model. Internal consistency of scales was very good and convergent correlations
      with the Big Five Inventory (BFI; John, Donahue, & Kentle, 1991) were
      substantial. Face validity, as evaluated by 2 independent raters, was good.
      Preliminary evidence of validity for the checklist is presented. Finally, the
      Adjective Checklist for Personality Assessment and BFI are compared, taking into
      consideration their psychometric properties in our cultural context. Study
      limitations and future research are discussed.

PMID- 21184331
TI  - Evaluation of a domain-specific anger expression assessment strategy.
AB  - Previous studies have shown that self-reports of an individual's anger expression
      vary between the home and the work domain. The aim of this study was to
      investigate the validity of such self-reports by comparing them with reports of
      intimate partners and work colleagues in the respective domain. Participants (N=
      86) rated their anger expression on the general and on domain-specific versions
      of the State-Trait-Anger Expression Inventory (Spielberger, 1988). The self-rated
      anger-out-home scores correlated highly with partner ratings of anger-out-home
      scores (r = .61) and colleague ratings of anger-out-work scores correlated
      substantially with self-rated anger-out-work scores (r = .54). A similar but
      weaker correlation pattern emerged for anger control but not for anger-in. Self
      other correspondence was higher for the domain-specific anger expression
      assessment than for the general anger expression assessment. These results
      demonstrate that the domain-specific strategy for the assessment of self-reported
      anger expression can validly measure differences in anger expression in different
      domains.

PMID- 21184332
TI  - A brief inventory of Interpersonal Problems-Circumplex using nonparametric item
      response theory: introducing the IIP-C-IRT.
AB  - Nonparametric item response theory methods were applied to the responses of 1,000
      college students on the 64 items of the Inventory of Interpersonal Problems
      Circumplex (IIP-C; Alden, Wiggins, & Pincus, 1990) to develop an abbreviated 32
      item version of the instrument. In a separate validation sample of 981 students,
      the newly selected scale items did not show evidence of differential item
      functioning across males and females. There was high convergence found between
      the new scales and IIP-C parent scales, along with commensurate or improved fits
      to the circular structural model relative to the full scale and its existing
      brief derivatives-the IIP-32 and the IIP-SC. Results provide evidence that the
      new brief scales can improve the level of precision and information yielded in
      brief assessments of interpersonal problems without gender bias.

PMID- 21184333
TI  - Depression, anxiety, and the MCMI-III: construct validity and diagnostic
      efficiency.
AB  - This study aimed to enhance knowledge of the construct validity and diagnostic
      efficiency of the depression- and anxiety-related scales of the MCMI-III (Millon,
      1994). The MCMI-III, various concurrent depression and anxiety measures, and an
      Axis I structured diagnostic interview were administered in a total sample of 696
      outpatients with depressive disorders, anxiety disorders, or both. Sound
      construct validity was found for the Dysthymia and Major Depression clinical
      syndrome scales and the Avoidant and Depressive personality disorder scales. The
      validity of the Anxiety scale was poor, showing moderate convergence with panic
      and worry-related anxiety measures, but problems discriminating from depression.
      Operating characteristics for discriminating depressed patients from anxious
      patients were fair for the Major Depression scale, but poor for the Anxiety and
      Dysthymia scales.

PMID- 21184334
TI  - The QCAE: a Questionnaire of Cognitive and Affective Empathy.
AB  - Empathy has been inconsistently defined and inadequately measured. This research
      aimed to produce a new and rigorously developed questionnaire. Exploratory (n1 =
      640) and confirmatory (n2 = 318) factor analyses were employed to develop the
      Questionnaire of Cognitive and Affective Empathy (QCAE). Principal components
      analysis revealed 5 factors (31 items). Confirmatory factor analysis confirmed
      this structure in an independent sample. The hypothesized 2-factor structure
      (cognitive and affective empathy) was tested and provided the best and most
      parsimonious fit to the data. Gender differences, convergent validity, and
      construct validity were examined. The QCAE is a valid tool for assessing
      cognitive and affective empathy.

PMID- 21184335
TI  - The FAD-Plus: measuring lay beliefs regarding free will and related constructs.
AB  - We describe the development of FAD-Plus, a 27-item measure of lay beliefs in free
      will and 3 closely related constructs: scientific determinism, fatalistic
      determinism, and unpredictability. Previously published measures included only a
      subset of these variables and tended to assume an a priori pattern of relations
      among these 4 beliefs. In Study 1, exploratory factor analyses suggested
      relatively independent factors. This independence was sustained in Study 2, using
      a confirmatory analysis. Each of the 4 subscales (Free Will, Scientific
      Determinism, Fatalistic Determinism, and Unpredictability) showed acceptable
      internal consistencies. Study 2 also mapped out associations with the Big Five
      personality traits and showed that believing in free will is not synonymous with
      having an internal locus of control. Study 3 replicated the instrument's
      structure and subscale reliabilities in a community sample. Preliminary
      applications are described.

PMID- 21184338
TI  - Female sexual pain disorders and cognitive behavioral therapy.
AB  - Female sexual pain disorders are prevalent and have a deleterious effect on
      women's well-being. Because there are psychological elements to this pain,
      cognitive-behavioral therapy (CBT) may be a viable treatment alternative,
      particularly when compared to more physically invasive treatments such as surgery
      or medication. This article provides a critical analysis of research studies in
      this area by evaluating each study in detail, identifying gaps in the research
      base, and providing directions for future study. For the most part, all of the
      studies reviewed in this article found CBT to be effective. However, CBT
      modalities with minimal therapist direction or interaction were found to be
      problematic. In addition, there may be other noninvasive treatment types that are
      equally or more effective, such as biofeedback or supportive psychotherapy.

PMID- 21184339
TI  - The best is yet to come: positive developments for the journal of sex research.

PMID- 21184340
TI  - Changes in running mechanics using conventional shoelace versus elastic shoe
      cover.
AB  - The purpose of this study was to determine whether there are differences in the
      perceived comfort, plantar pressure, and rearfoot motion between laced running
      shoes and elastic-covered running shoes. Fifteen male amateur runners
      participated in the study. Each participant was assigned laced running shoes and
      elastic-covered running shoes for use during the study. The perceived comfort,
      plantar loading, and rearfoot motion control of each type of shoes during running
      were recorded. When the laced running shoes and elastic-covered running shoes
      were compared, the elastic-covered running shoes were given a lower perceived
      comfort rating in terms of shoe length, width, heel cup fitting, and forefoot
      cushioning. The elastic-covered running shoes also recorded higher peak plantar
      pressure in the lateral side of the forefoot, as well as larger maximum rearfoot
      pronation. Overall, shoelaces can help runners obtain better foot-shoe fit. They
      increase the perceived comfort, and decrease the maximum pronation and plantar
      pressure. Moreover, shoelaces may help prevent injury in running by allowing
      better control of the aforementioned factors.

PMID- 21184342
TI  - Coaching competency and satisfaction with the coach: a multi-level structural
      equation model.
AB  - The purpose of this initial predictive validity study was to determine the
      ability of measures derived from the Athletes' Perceptions of Coaching Competency
      Scale II - High School Teams (APCCS II-HST) to predict satisfaction with the head
      coach. Specification of the statistical model was informed by the mediational
      model of coach-athlete interactions. The technical quality of the satisfaction
      measure was evaluated before testing the predictive validity of the coaching
      competency measures. Data were collected from athletes of seven sports. Athlete
      observations (N = 748) were clustered within teams (G = 74). Multi-group
      confirmatory factor analyses (CFA) provided evidence for factorial invariance of
      a reduced version of the satisfaction measure by athlete gender. Multi-level CFA
      provided evidence of model-data consistency for a reduced version of the
      satisfaction measure. Multi-level structural equation modelling provided evidence
      for the ability of latent coaching competency to positively predict latent
      satisfaction at both the athlete level (technique competency and motivation
      competency) and the team level (coaching competency) and for close model-data
      fit. Implications of this study include: that the APCCS II-HST should be viewed
      as a replacement for the Coaching Competency Scale when the intended population
      is appropriate; a preliminary multi-level measurement model for satisfaction with
      one's coach that should be considered as a potential starting point in subsequent
      studies; and empirical support for a key relationship proposed in the mediational
      model of coach-athlete interactions.

PMID- 21184341
TI  - Monitoring markers of muscle damage during a 3 week periodized drop-jump exercise
      programme.
AB  - The aim of this study was to examine changes in indirect markers of muscle damage
      during 3 weeks of stretch-shortening exercise with a progressively increasing
      load and continued modulation of various key training variables. Eight healthy
      untrained men performed a drop-jump programme involving a progressive increase in
      load impact with respect to the number of jumps performed, drop (platform)
      height, squat depth amplitude, and addition of weights. Maximal concentric and
      isometric knee extensor strength were assessed immediately before and 10 min
      after each training session. Voluntary and 100 Hz-stimulation-evoked torque
      decreased acutely after each training session relative to pre-exercise values (P
      < 0.05) but recovered before the subsequent training session. Post-exercise
      plasma creatine kinase activity increased from 162.2 +/- 56.2 IU . l(-1) to 284.3
      +/- 116.3 IU . l(-1) at 48 h after the first training session (P < 0.05) and
      remained marginally elevated throughout the training period. The present results
      indicate that detrimental muscle damage can be avoided with drop-jump training
      even with the gradual introduction of more demanding exercise induced by
      increasing the volume, intensity, and muscle stretch amplitude. These findings
      suggest that the human neuromuscular system is highly adaptable to progressively
      varied loading demands during stretch-shortening exercise training.

PMID- 21184343
TI  - Physical activity among Spanish adolescents: relationship with their relatives'
      physical activity - the AVENA study.
AB  - Identifying factors related to physical activity levels in young people is
      important for a more efficient health promotion. The aims of this study were to
      assess physical activity levels in a national sample of urban Spanish
      adolescents, and to examine the association between significant others' physical
      activity (father, mother, brother, sister, and close friends) and that of the
      adolescents. The present study comprised 2260 adolescents (1157 boys, 1103 girls)
      aged 13.0-18.5 years participating in the AVENA Study. Both the adolescents'
      physical activity and that of their relatives and close friends was assessed by
      questionnaire. The odds of being active were higher in boys than girls (odds
      ratio = 2.79, 95% confidence interval = 2.34-3.33) and tended to decrease across
      age groups in both boys and girls. Father's and older brother's physical activity
      was associated with boys' physical activity, while that of any significant other
      was associated with girls' physical activity. When both parents reported being
      active, boys had nearly two times higher odds of being active and girls had
      nearly three times higher odds of being active. The physical activity levels of
      Spanish adolescents are in line with those previously reported. Physical activity
      levels in girls are strongly related to the physical activity of any significant
      other, whereas physical activity levels in boys are only related to their male
      relatives' physical activity.

PMID- 21184344
TI  - Body image, perceived and actual physical abilities in normal-weight and
      overweight boys involved in individual and team sports.
AB  - The aim of the study was to examine the relationships among body image,
      perception of physical abilities, and motor performance in boys involved in
      organized individual (i.e. tennis, fencing, judo) and team (i.e. soccer,
      handball, volleyball) sports. Altogether, 162 children (12.6 +/- 1.0 years) were
      categorized as normal-weight (n = 85) or overweight (n = 77). Body image was
      measured using Collins' Child Figure Drawings, while individuals' perceptions of
      strength, speed, and agility were assessed using the Perceived Physical Ability
      Scale. Fitness tests of the standing long jump, 20 m sprint, and 10 * 5 m shuttle
      run were also administered. Overweight boys showed greater body dissatisfaction
      and lower actual physical abilities than normal-weight peers. Participants
      involved in team sports reported lower body dissatisfaction and better
      performances in the shuttle-run compared with those involved in individual
      sports. For boys participating in team sports, body dissatisfaction was a
      significant mediator of the effect of body mass index on perceived physical
      ability. Results may influence intervention efforts, suggesting that targeting
      personal, psychological, and physical factors may prove efficient across physical
      activity locations and weight groups.

PMID- 21184345
TI  - Metamotivational state and dominance: Links with EMG gradients during isokinetic
      leg extension and a test of the misfit effect.
AB  - Although electromyographic (EMG) gradients have been observed in passive
      musculature during perceptual motor tasks, it is unclear whether this is related
      to metamotivational state or dominance. In addition, a misfit effect has been
      suggested whereby individuals report negative psychological responses when
      metamotivational state and dominance do not match. Research examining these
      phenomena within an exercise context is limited; therefore, this study used a
      reversal theory (Apter, 2001) framework to examine two hypotheses. The first
      hypothesis was that an EMG gradient would be observed when individuals performed
      isokinetic leg extensions in a telic metamotivational state, regardless of telic
      or paratelic metamotivational dominance. Second, it was hypothesizsed that telic
      dominant individuals and paratelic-dominant individuals would perform better on
      this task when in the telic and paratelic state, respectively. Altogether, 14
      telic-dominant and 12 paratelic-dominant individuals performed 100 self-paced
      isokinetic leg extensions at a rate of 90 degrees  . s(-1) in both telic and
      paratelic state manipulated conditions. Regardless of state, an EMG gradient was
      observed in telic-dominant individuals but not in paratelic-dominant individuals.
      Paratelic-dominant individuals performed better in the paratelic than the telic
      state condition, whereas in the telic state condition, telic-dominant individuals
      performed better than paratelic-dominant individuals. Findings add to the debate
      concerning the role of telic metamotivational state and dominance in the
      production of EMG gradients. Performance data support the misfit effect that
      outcomes are more positive when metamotivational state and dominance are
      congruent. Suggestions for research developments in this area are offered, as are
      tentative implications for applied practice.

PMID- 21184346
TI  - Net efficiency of roller skiing with a diagonal stride.
AB  - The aims of this study were: (a) to determine net efficiency during roller skiing
      with a diagonal stride at various speeds; (b) to assess the development of net
      efficiency across speeds; and (c) to examine the characteristics of efficiency in
      diagonal roller skiing. Two-dimensional kinematics and oxygen uptake were
      determined in eight male collegiate cross-country ski athletes who roller skied
      with the diagonal stride at various speeds on a level track. Net efficiency was
      calculated from rates of internal and external work and net energy expenditure.
      Individual net efficiency ranged from 17.7% to 52.1%. Net efficiency in the
      entire group of athletes increased with increasing speed, reached a maximum value
      of 37.3% at 3.68 m . s(-1), before slowly decreasing. These findings indicate
      that roller skiing with the diagonal stride at high speed is a highly efficient
      movement and that an optimal speed exists at which net efficiency can be
      maximally enhanced in diagonal roller skiing.

PMID- 21184347
TI  - Evaluation of the exercise workload of broadcast calisthenics for children and
      adolescents aged 11-17 years.
AB  - The aim of this study was to examine the exercise workload of the 3rd Series of
      National Broadcast Calisthenics for Elementary and Middle School Students.
      Altogether, 120 students aged 11-17 years were randomly selected from elementary
      and middle schools to participate in the study. Each participant performed a
      cycle ergometer test to obtain maximum oxygen uptake ([Vdot]O(2max)) and maximum
      heart rate values. In the laboratory, oxygen uptake ([Vdot]O(2)), metabolic
      equivalents (METs), and heart rate were recorded continuously throughout a
      calisthenics session performed by the participants. Ratings of perceived exertion
      (RPE) were also recorded. Throughout the calisthenics session, mean percentage of
      [Vdot]O(2) reserve varied from 30.7% to 41.2%, mean percentage of heart rate
      reserve from 39.0% to 56.9%, and mean RPE from 9.0 to 10.4. The mean energy cost
      during most of the segments across the four routines of calisthenics was
      significantly higher (P < 0.05) than 3.0 METs. In conclusion, the exercise
      workload of the 3rd Series of National Broadcast Calisthenics for Elementary and
      Middle School Students session varied from low to moderate. As part of a school
      based physical activity intervention project, calisthenics would help to promote
      an active lifestyle and health in children and adolescents.

PMID- 21184348
TI  - Simulated dyslexia in postsecondary students: description and detection using
      embedded validity indicators.
AB  - The current investigation identified characteristics that discriminated authentic
      dyslexia from its simulation using measures common to postsecondary learning
      disability evaluations. Analyses revealed accurate simulation on most achievement
      measures but inaccurate feigning on neurolinguistic processing measures, speed on
      timed tasks, and error quantity. The largest group separations were on rapid
      naming, speeded orthographic, and reading fluency tasks. Simulators accurately
      feigned dyslexia profiles on cut-score and discrepancy diagnostic models but not
      on the more complex aspects of the clinical judgment model. Regarding simulation
      detection, a multivariate rule exhibited the greatest classification accuracy,
      followed by univariate indices developed from rapid naming tasks. The findings of
      the current study suggest that aspects of a comprehensive evaluation may aid in
      the detection of simulated dyslexia.

PMID- 21184349
TI  - Editors' introduction to the issue: theoretical ideas in motor neuroscience and
      their capacity for falsification.

PMID- 21184350
TI  - Experimenting with theoretical motor neuroscience.
AB  - Motor neuroscience is well over 100 years old, with seminal work such as G. T.
      Fritz and E. Hitzig's discovery of motor cortex occurring in 1870. Theoretical
      motor neuroscience has been ongoing for at least the last 50 years. How mature a
      scientific discipline is motor neuroscience? Are experimentalists and
      theoreticians working together productively to help the field progress? This
      article addresses these questions by advancing the following theses. Motor
      neuroscience remains at a descriptive stage due to the incredible complexity of
      the problem to be solved. The proliferation of models--and distinct modeling
      camps--stems from the absence of unifying conceptual constructs. To advance the
      field, theoreticians must rely more heavily on the concept of falsification by
      producing models that lend themselves to clear experimental testing.

PMID- 21184351
TI  - In praise of "false" models and rich data.
AB  - The authors argue that "true" models that aim at faithfully mimicking or
      reproducing every property of the sensorimotor system cannot be compact as they
      need many free parameters. Consequently, most scientists in motor control use
      what are called "false" models--models that derive from well-defined
      approximations. The authors conceptualize these models as a priori limited in
      scope and approximate. As such, they argue that a quantitative characterization
      of the deviations between the system and the model, more than the mere act of
      falsifying, allows scientists to make progress in understanding the sensorimotor
      system. Ultimately, this process should result in models that explain as much
      data variance as possible. The authors conclude by arguing that progress in that
      direction could strongly benefit from databases of experimental results and
      collections of models.

PMID- 21184352
TI  - Brain-computer interface research comes of age: traditional assumptions meet
      emerging realities.
AB  - Brain-computer interfaces (BCIs) could provide important new communication and
      control options for people with severe motor disabilities. Most BCI research to
      date has been based on 4 assumptions that: (a) intended actions are fully
      represented in the cerebral cortex; (b) neuronal action potentials can provide
      the best picture of an intended action; (c) the best BCI is one that records
      action potentials and decodes them; and (d) ongoing mutual adaptation by the BCI
      user and the BCI system is not very important. In reality, none of these
      assumptions is presently defensible. Intended actions are the products of many
      areas, from the cortex to the spinal cord, and the contributions of each area
      change continually as the CNS adapts to optimize performance. BCIs must track and
      guide these adaptations if they are to achieve and maintain good performance.
      Furthermore, it is not yet clear which category of brain signals will prove most
      effective for BCI applications. In human studies to date, low-resolution
      electroencephalography-based BCIs perform as well as high-resolution cortical
      neuron-based BCIs. In sum, BCIs allow their users to develop new skills in which
      the users control brain signals rather than muscles. Thus, the central task of
      BCI research is to determine which brain signals users can best control, to
      maximize that control, and to translate it accurately and reliably into actions
      that accomplish the users' intentions.

PMID- 21184353
TI  - Neural correlates of skill acquisition with a cortical brain-machine interface.
AB  - Research into the development of brain-machine interfaces (BMIs) has led to
      demonstrations of rodents, nonhuman primates, and humans controlling prosthetic
      devices in real time through modulation of neural signals. In particular,
      cortical BMI studies have shown that improvements in performance require learning
      and are associated with changes in neuronal tuning properties. These studies have
      further shown evidence of long-term improvements in performance with practice.
      The authors conducted experiments to understand long-term skill acquisition with
      BMIs and to characterize the neural correlates of improvements in task
      performance. They specifically assessed long-term acquisition of neuroprosthetic
      skill (i.e., accurate task performance readily recalled across days). In 2
      monkeys performing a center-out task using a brain-controlled (BC) computer
      cursor, they closely monitored daily performance trends and the neural correlates
      under different conditions. Importantly, they assessed BC performance using a
      continuous-control multistep task. The authors first conducted experiments that
      mimicked experimental conditions commonly used. Specifically, a large set of
      neurons was incorporated with daily recalibration of the transform of neural
      activity to BC. Under such conditions, they found evidence of variable daily
      performance. In contrast, when a fixed transform was applied to stable recordings
      from an ensemble of neurons across days, there was consistent evidence of long
      term skill acquisition. Such skill acquisition was associated with the
      crystallization of a cortical map for prosthetic control. Taken together, the
      results suggest that the primate motor cortex can achieve skilled control of a
      neuroprosthetic device through consolidation of a cortical representation.

PMID- 21184354
TI  - Modularity for sensorimotor control: evidence and a new prediction.
AB  - By combining a few modules, the CNS may learn new control policies quickly and
      efficiently. Support for a modular organization of the motor system has recently
      come from the observation of low dimensionality in the motor commands. However,
      stronger evidence would come from testing the predictions on the effect of an
      intervention on the mechanisms required to implement a modular controller. Thus,
      the authors propose to test the predictions of modularity on motor adaptation.
      They argue that unlike a nonmodular controller, a modular controller must adapt
      faster to a perturbation that is compatible with the modules (i.e., one that can
      be compensated by reusing the same modules), than to an incompatible perturbation
      (i.e., one that requires new modules).

PMID- 21184355
TI  - Evidence for model-based action planning in a sequential finger movement task.
AB  - In this article, the authors examine whether and how humans use model-free,
      reflexive strategies and model-based, deliberative strategies in motor sequence
      learning. They asked subjects to perform the grid-sailing task, which required
      moving a cursor to different goal positions in a 5 * 5 grid using different key
      mapping (KM) rules between 3 finger keys and 3 cursor movement directions. The
      task was performed under 3 conditions: Condition 1, new KM; Condition 2, new goal
      position with learned KM; and Condition 3, learned goal position with learned KM;
      with or without prestart delay time. The performance improvement with prestart
      delay was significantly larger under Condition 2. This result provides evidence
      that humans implement a model-based strategy for sequential action selection and
      learning by using previously learned internal model of state transition by
      actions.

PMID- 21184356
TI  - Why professional athletes need a prolonged period of warm-up and other
      peculiarities of human motor learning.
AB  - Professional athletes involved in sports that require the execution of fine motor
      skills must practice for a considerable length of time before competing in an
      event. Why is such practice necessary? Is it merely to warm-up the muscles,
      tendons, and ligaments, or does the athlete's sensorimotor network need to be
      constantly recalibrated? In this article, the authors present a point of view in
      which the human sensorimotor system is characterized by: (a) a high noise level
      and (b) a high learning rate at the synaptic level (which, because of the noise,
      does not equate to a high learning rate at the behavioral level). They argue that
      many heuristics of human skill learning, including the need for a prolonged
      period of warm-up in experts, follow from these assumptions.

PMID- 21184357
TI  - Bouncing between model and data: stability, passivity, and optimality in hybrid
      dynamics.
AB  - Rhythmically bouncing a ball with a racket is a seemingly simple task, but it
      poses all the challenges critical for coordinative behavior: perceiving the
      ball's trajectory to adapt position and velocity of the racket for the next ball
      contact. To gain insight into the underlying control strategies, the authors
      conducted a series of studies that tested models with experimental data, with an
      emphasis on deriving model-based hypotheses and trying to falsify them. Starting
      with a simple dynamical model of the racket and ball interactions, stability
      analyses showed that open-loop dynamics affords dynamical stability, such that
      small perturbations do not require corrections. To obtain this passive stability,
      the ball has to be impacted with negative acceleration--a strategy that subjects
      adopted in a variety of conditions at steady state. However, experimental tests
      that applied perturbations revealed that after perturbations, subjects applied
      active perceptually guided corrections to reestablish steady state faster than by
      relying on the passive model's relaxation alone. Hence, the authors derived a
      model with active control based on optimality principles that considered each
      impact as a separate reaching-like movement. This model captured some additional
      features of the racket trajectory but failed to predict more fine-grained aspects
      of performance. The authors proceed to present a new model that accounts not only
      for fine-grained behavior but also reconciles passive and active control
      approaches with new predictions that will be put to test in the next set of
      experiments.

PMID- 21184358
TI  - Controlling variability.
AB  - In human motor control, there is uncertainty in both estimation of initial
      sensory state and prediction of the outcome of motor commands. With practice,
      increasing precision can often be achieved, but such precision incurs costs in
      time, effort, and neural resources. Therefore, motor planning must account for
      variability, uncertainty, and noise, not just at the endpoint of movement but
      throughout the movement. The author presents a mathematical basis for
      understanding the time course of uncertainty during movement. He shows that it is
      possible to achieve accurate control of the endpoint of a movement even with
      highly inaccurate and variable controllers. The results provide a first step
      toward a theory of optimal control for variable, uncertain, and noisy systems
      that must nevertheless accomplish real-world tasks reliably.

PMID- 21184360
TI  - Food-borne illness: high stakes health threat for older adults.

PMID- 21184361
TI  - Food Safety Knowledge and Practices among Older Adults: Identifying Causes and
      Solutions for Risky Behaviors.
AB  - Adults aged 60 years and older are more likely than younger adults to experience
      complications, hospitalization, and death because of food-borne infections.
      Recognizing this risk, we conducted a nationally representative survey (n =
      1,140) to characterize older adults' food safety knowledge, attitudes, and
      practices as well as the demographic characteristics of older adults with risky
      food handling practices. The survey was conducted using a Web-enabled panel. We
      found that although older adults consider themselves to be knowledgeable about
      food safety, many are not following recommended food safety practices. Areas for
      improvement include the following: reheating deli meats to steaming hot, not
      eating store-bought deli salads, cooking eggs properly, monitoring refrigerator
      temperature using a thermometer, using a food thermometer to check doneness of
      meat/poultry/egg dishes, and storing leftovers properly. The survey results also
      suggest that food safety education targeting older adults is needed and that such
      initiatives should emphasize practices to prevent listeriosis, a potentially
      fatal illness among older adults. Our findings suggest that, in particular, men,
      individuals with higher incomes, and college-educated individuals would benefit
      from food safety education.

PMID- 21184362
TI  - Challenges in the delivery of nutrition services to hospital discharged older
      adults: the community connections demonstration project.
AB  - The objective of this project was to explore the effort necessary to transform
      the Older Americans Act Nutrition Program (OAANP) into core programs within an
      integrated health care delivery system that serves hospital-discharged older
      adults in order to assist them in reintegrating into the community. Six OAANPs in
      six states were funded and provided technical assistance to develop coalitions
      with hospitals and community organizations. Each demonstration site was unique
      and faced many challenges in reaching out to a hospitalized vulnerable
      population. This project also provided opportunities to try out new initiatives
      and examine their sustainability within the community.

PMID- 21184363
TI  - The relationships between food group consumption, self-rated health, and life
      satisfaction of community-dwelling canadian older men: the manitoba follow-up
      study.
AB  - We conducted a cross-sectional evaluation nested within a long-term cohort study
      that was designed to examine the relationship between frequency of food group
      consumption (FGC), self-rated health, and life satisfaction of community-dwelling
      older men in the Manitoba Follow-up Study. Questionnaires returned from 1,211
      Canadian male participants contained frequency of FGC (daily, most days, or
      rarely), self-reported nutrition, and health-related perceptions. Men consuming
      vegetables/fruit (V&F) daily versus rarely were four times more likely to report
      better self-rated health OR = 4.00 (95%CI = 1.31, 12.3) and three times more
      likely to rate greater life satisfaction OR = 3.08 (95%CI = 1.00, 9.45). Our
      findings indicate that frequent consumption of V&F is associated with the
      perception of better health and greater life satisfaction.

PMID- 21184364
TI  - Reasons given by homebound older adults living in a large midwestern city for
      taking or not taking vitamin and mineral supplements.
AB  - The prevalence of vitamin and mineral supplement usage in a group of homebound
      older adults in a large Midwestern city and their motivation for supplement use
      or nonuse were evaluated. Sixty-one selected homebound individuals 60 years and
      older from three assistance programs for older adults participated in the study.
      Forty-seven percent reported taking vitamin or mineral supplements, and of these
      93% were taking a multivitamin supplement. Most participants received their
      information regarding supplements from a health care professional, generally a
      physician. For those not taking supplements, the most common reason given was the
      absence of a prescription/recommendation. For those taking supplements, the most
      common reason given was that supplements were prescribed/recommended.

PMID- 21184365
TI  - A home-based nutrition and physical activity intervention for grandparents
      raising grandchildren: a pilot study.
AB  - Five African American grandparents raising their grandchildren participated in a
      home-based nutrition and physical activity intervention. The primary goals were
      to increase grandparents' knowledge and skills in selecting and preparing healthy
      foods and to increase the grandparents' and grandchildren's physical activity
      levels. Results revealed that grandparents' concerns regarding their chronic
      diseases and desire to prevent health problems in their grandchildren served as
      motivators. Following the intervention, grandparents scored higher on nutrition
      and physical activity knowledge and their self-efficacy improved, although most
      health status indicators remained unchanged. Self-reported changes included
      walking more, reading food labels, and switching to a healthier type of fat.

PMID- 21184366
TI  - Helpful web sites for food safety and older adults.
AB  - When it comes to Food Safety in the U.S. there is not just one government agency
      responsible for a safe food supply, the Food Drug Administration (FDA), United
      States Department of Agriculture (USDA), and the Centers for Disease Control
      (CDC) play key roles. The links below are geared toward food safety guidance for
      older adults, who are particularly at risk. SOURCE: Cates et al.

PMID- 21184367
TI  - Alcohol and the older adult: a comprehensive review.
AB  - Alcohol consumption in the older adult is of major concern with the advent of
      baby boomers coming into the over 65-age bracket. Alcohol consumption has been
      touted as beneficial for health, and while that may be accurate for moderate
      consumption in younger persons, there is considerable risk associated with
      increased alcohol intake in older adults. This increase is partially due to age
      related physiological changes, existing diagnoses, number of comorbid conditions,
      and increased use of prescribed and/or over-the-counter medications, coupled with
      other concerns. This review addresses the current research regarding ethanol
      consumption in older adults and all-cause mortality as well as several conditions
      more frequently seen in the geriatric population. These conditions include
      vascular diseases, hypertension, type 2 diabetes, gastrointestinal disorders,
      hepatic disorders, dental and oro-facial problems, bone density decline, and
      falls and fractures. In addition, drug interactions and recent research into
      select vitamin and mineral considerations with increased alcohol intake in older
      persons are addressed. While recommendations for alcohol intake have not been
      specifically established for age ranges within the 65-year-and-older bracket, and
      practitioners do not routinely assess alcohol intake or ethanol related adverse
      events in this population, common sense approaches to monitoring will become
      increasingly important as the generation of "boomers" who believe that alcohol
      intake improves health comes of age.

PMID- 21184368
TI  - Use of calcium, folate, and vitamin D3-fortified milk for 6 months improves
      nutritional status but not bone mass or turnover, in a group of Australian aged
      care residents.
AB  - In residential care, inadequate calcium and folate intakes and low serum vitamin
      D (25(OH)D) concentrations are common. We assessed whether daily provision of
      calcium, folate, and vitamin D3-fortified milk for 6 months improved nutritional
      status (serum micronutrients), bone quality (heel ultrasound), bone turnover
      markers (parathyroid hormone, C-terminal collagen I telopeptide, terminal
      propeptide of type I procollagen), and/or muscle strength and mobility in a group
      of Australian aged care residents. One hundred and seven residents completed the
      study (mean (SD) age: 79.9 (10.1) years; body weight: 68.4 (15.4) kg). The median
      (inter-quartile range) volume of fortified milk consumed was 160 (149) ml/day. At
      the end of the study, the median daily vitamin D intake increased to 10.4 (8.7)
      MUg (P < .001), which is 70% of the adequate intake (15 MUg); and calcium density
      (mg/MJ) was higher over the study period compared with baseline (161 +/- 5 mg/MJ
      vs. 142 +/- 4 mg/MJ, P < .001). Serum 25(OH)D concentrations increased by 23 +/-
      2 nmol/L (83 (107)%, P < .001), yet remained in the insufficient range (mean 45
      +/- 2 nmol/L). Consumption of greater than the median intake of milk (160 ml/day)
      (n = 54, 50%) increased serum 25(OH)D levels into the adequate range (53 +/- 2
      nmol/L) and reduced serum parathyroid hormone by 24% (P = .045). There was no
      effect on bone quality, bone turnover markers, muscle strength, or mobility.
      Consumption of fortified milk increased dietary vitamin D intake and raised serum
      25(OH)D concentrations, but not to the level thought to reduce fracture risk. If
      calcium-fortified milk also was used in cooking and milk drinks, this approach
      could allow residents to achieve a dietary calcium intake close to recommended
      levels. A vitamin D supplement would be recommended to ensure adequate vitamin D
      status for all residents.

PMID- 21184370
TI  - Nutrition education improves morale and self-efficacy for middle-aged and older
      women.
AB  - This study aimed to improve dietary compliance, attitudes, morale, and self
      efficacy for 58 community-residing women ages 54-83 years regarding heart healthy
      dietary practices using a randomized control group design in two North Carolina
      counties. Questionnaires administered prior to Visits 1 (Baseline) and 4 (Day 90)
      and three 3-day food records were completed within 1 week of Visit 1 and 28-30
      days thereafter. Treatment included two individual counseling sessions using pre
      tested materials: Controls received corresponding mailings. Data analyses
      included descriptive statistics, analysis of covariance, correlations, and paired
      sample t-tests. Collective (total group) and control morale improved (p <= 0.01).
      The efficacy construct "ability to choose healthy foods" improved collectively (p
      < 0.0001). Compliance correlated (p <= 0.05) with the ability to follow special
      dietary regimens collectively and by group. Treatment Compliance correlated (p <=
      0.03) with the ability to choose healthy foods and morale. No significant between
      group differences were noted. Tailored nutrition programs empowered older women
      regarding their nutritional health improve morale and self-efficacy. In-home or
      mailed education materials with follow-up may be equally effective with similar
      older women in other locations.

PMID- 21184369
TI  - Measuring the impact of nutrition education and physical activity on older adults
      participating in government sponsored programs.
AB  - A longitudinal, four-year study (2004-2007) with a cohort of 139 older adults
      (majority women;71%) was conducted to examine the impact of community-based
      nutrition and physical activity programs on health outcome measures. Demographic
      and anthropometric data were collected and nutrition screening was performed.
      Blood pressure, serum cholesterol and glucose levels, and pulse rate were also
      measured. The blood pressure, both mean systolic and diastolic, 141(+/-
      19.0)/79.3 +/- 9.7 (2004) vs. 127.8 +/- 10.9/73.8 +/- 10.2 mm Hg (2007), were
      improved (p < 0.05) in women. There were also improvements (p < 0.05 in both men
      and women) in pulse rate between 2004 and 2007. There is no doubt that nutrition
      education and exercise programs together enhanced the overall health and well
      being of these older adults. However, our findings emphasize the need for further
      systematic study and for appropriate biometric assessments to evaluate the full
      impact of nutrition education and physical activity interventions in older
      adults.

PMID- 21184371
TI  - Anthropometric and dietary evaluations in a sample of "healthy" Mexican older
      adults.
AB  - The purpose of this study was to describe anthropometric, metabolic, and
      nutritional characteristics in healthy elderly adults in a primary health care
      setting. It was conducted through a cross-sectional study of 80 subjects 60 years
      of age and older. After confirming healthy status, clinical, biochemical,
      dietetic, and anthropometric evaluations were performed. The findings indicated
      22% had anemia, 22% had impaired glucose tolerance, 46% had hypertriglyceridemia,
      and 51% had hypercholesterolemia. More than 50% had obesity, and almost 80% had a
      high risk waist circumference measure. Mean energy intake was normal; however,
      more than 50% of participants did not have adequate intakes of potassium,
      calcium, magnesium, zinc, folic acid, and vitamins B(12) and A. Inadequate food
      intakes were common. Specific examples are that 16% of the subjects ate no
      meat/egg, 31% ate no dairy products, 56% ate no legumes, 22% ate no fruits, and
      41% ate no vegetables. Additionally, 31% consumed soft drinks. Therefore, we can
      conclude that elderly people otherwise considered as "healthy" nonetheless had a
      high proportion of obesity and cardiovascular risk factors. Inadequate dietary
      patterns were also observed and corresponded with poor micronutrient intake.

PMID- 21184372
TI  - Prevalence of chronic energy deficiency in rural-dwelling older Indian adults
      during a period of severe drought.
AB  - The prevalence of chronic energy deficiency (CED = BMI < 18.5) among older adults
      (>=60 years) was assessed utilizing a large data set from a community-based cross
      sectional study carried out in severely drought-affected rural areas of India.
      Anthropometric measurements (height, weight) were recorded for a total of 3,147
      individuals, and a family diet survey (one day 24-hour recall) was carried out in
      1,900 households (HHs) from 190 villages. As per the Body Mass Index (BMI), the
      prevalence of CED was 51.1% and 48.5% among older males and females,
      respectively. It was higher (p < 0.001) in the 70 years and older age group
      compared with those aged 60-69 years. In general, the prevalence of CED was
      higher (p < 0.001) for those belonging to the Scheduled Caste and Scheduled
      Tribes, for HHs of agricultural and non-agricultural labor, and for marginal or
      small farmers. The prevalence of CED was relatively lower (p > 0.05) among older
      adults during the drought period compared with the non-drought period. This could
      be attributed to intervention programs initiated by the government of India
      during the drought. These findings illustrate the value of intervention programs
      in drought-afflicted and drought-prone areas and underscore the importance of
      monitoring the nutritional status of older adults so that appropriate programs
      can be initiated as needed.

PMID- 21184373
TI  - Prevalence of undernutrition in a long-term care facility in Qatar.
AB  - This study assessed the nutritional status of 130 Qatari patients aged 65 to 90
      years who were residing in a long-term care facility for six months. Admission
      weight was not measured for 49.2% of the subjects. Of those whose weight was
      measured at admission, assessment at six months indicated that 21.3% had lost
      more than 10% of their admission weight, 38.9% were under the fifth percentile of
      body mass index (BMI), 39.8% had a BMI less than 21, 27.1% had albumin level
      below 34 g/L, and 18.6% had total cholesterol below (140 mg/dl). The study showed
      a high prevalence of undernutrition among these long-term care residents and
      indicated that appropriate nutritional assessment and nutrition care were not
      fully implemented during their stay in the facility.

PMID- 21184376
TI  - Mealtimes in nursing homes: striving for person-centered care.
AB  - Malnutrition is a common and serious problem in nursing homes. Dietary strategies
      need to be augmented by person-centered mealtime care practices to address this
      complex issue. This review will focus on literature from the past two decades on
      mealtime experiences and feeding assistance in nursing homes. The purpose is to
      examine how mealtime care practices can be made more person-centered. It will
      first look at several issues that appear to underlie quality of care at
      mealtimes. Then four themes or elements related to person-centered care
      principles that emerge within the mealtime literature will be considered:
      providing choices and preferences, supporting independence, showing respect, and
      promoting social interactions. A few examples of multifaceted mealtime
      interventions that illustrate person-centered approaches will be described.
      Finally, ways to support nursing home staff to provide person-centered mealtime
      care will be discussed. Education and training interventions for direct care
      workers should be developed and evaluated to improve implementation of person
      centered mealtime care practices. Appropriate staffing levels and supervision are
      also needed to support staff, and this may require creative solutions in the face
      of current constraints in health care.

PMID- 21184378
TI  - Self-reported height, calculated height, and derived body mass index in
      assessment of older adults.
AB  - Body mass index (BMI) is frequently used as assessment of nutritional and health
      risk. Yet, there is no consensus regarding assessment of height and cutpoints for
      weight classification in older adults. We first investigated differences in
      height by self-report (SR-height) and height calculated from measured knee-height
      (KH-height) and derived BMI in a cross-sectional assessment of 145 older adults
      residing in a Midwestern United States city. We further compared the proportion
      of older adults classified as at risk by seven different BMI cutpoints for weight
      classification as reported in the literature. We found no substantive difference
      in SR-height and KH-height or derived BMI, but we did find significant
      differences in the proportions of participants classified as At Risk across
      different BMI cutpoints. In community and clinical practice, SR-height and KH
      height, and BMI derived from these, can be used interchangeably, but the lack of
      consensus regarding BMI cutpoints could lead to misclassification of older adults
      at risk.

PMID- 21184377
TI  - Natural food folate and late-life depression.
AB  - Low folate status has been linked to depression, but findings have been
      inconsistent. The authors sought to examine the association between folate intake
      and late-life depression. This cross-sectional study included individuals age 60
      and older (n = 111 depression, n = 136 comparison). Depression participants
      received psychiatric care. Folate and kilocalorie intakes were assessed with a
      Block 1998 food frequency questionnaire. Naturally occurring food folate was
      inversely associated with depression after controlling for age, sex, race,
      education, and total energy (P = 0.0047). All other folate variables including
      total dietary folate and folic acid were non-significant for depression. These
      findings may indicate that the naturally occurring form of folate is uniquely
      protective for depression and perhaps brain health. Alternatively, natural folate
      may be a surrogate for other nutrients or overall dietary quality.

PMID- 21184379
TI  - Race/Ethnicity differences in the relationship between obesity and gait speed
      among older Americans.
AB  - Projections indicate that the older American population will become more racially
      diverse in the future. Therefore, eliminating health disparities among older
      adults should be a public health priority. Using data from the 1999-2002 National
      Health and Nutrition Examination Survey, we examined the relationship between
      obesity, measured by BMI and waist circumference, and gait speed, a performance
      based measure of physical function, in 2,285 older adults (>=60 y) in order to
      determine whether this relationship varies by race/ethnicity. Overweight and
      obesity, indicated by a BMI >= 25 kg/m(2) and a waist circumference in quartiles
      3 (male: 102.4-109.9 cm; female: 97.3-106.3 cm) and 4 (male: 110.2-156.6 cm;
      female: 106.4-147.5 cm), were associated with slower gait speed in non-Hispanic
      Whites. Among non-Hispanic Blacks, only extreme obesity, indicated by a BMI >= 35
      kg/m(2) and a waist circumference in quartile 4 (male: 110.2-149.6 cm; female:
      106.4-137.7 cm), was associated with a slower gait speed. Among Mexican
      Americans, only extreme obesity, indicated by a BMI >= 35 kg/m(2), was associated
      with a slower gait speed. Thus we found the relationship between obesity and gait
      speed differed by race/ethnicity. The goal of eliminating health disparities in
      access to and quality of health care is only possible when differences in the
      associations between possible risk factors and physical function are identified.

PMID- 21184380
TI  - Vitamin D insufficiency among postmenopausal women in urban and rural areas in
      Guilan, Northern Iran.
AB  - This study aimed to describe vitamin D status in postmenopausal women in urban
      and rural areas in Guilan, northern Iran. Between October 2004 and February 2005
      a group of 750 women older than 50 years was randomly selected from urban and
      rural areas in Guilan. The participants were interviewed to collect data on age,
      educational level, body weight, height, employment status, reproductive history,
      medications, history of illness, and supplement use. Serum 25(OH) D was measured
      in 646 women (427 in urban areas and 219 women in rural areas). Serum 25(OH) D
      levels in urban and rural postmenopausal women were 18.5 +/- 13.5 ng/ml and 22.9
      +/- 13.8 ng/ml (P < 0.0001), respectively. In urban and rural areas, 84.7% and
      79.5% of the women had serum 25(OH) D levels less than 30 ng/ml, respectively. In
      this study, serum vitamin D levels and prevalence of vitamin D insufficiency was
      related to educational level in urban women. The urban women in the lowest
      educational level (<5 years schooling) had a better vitamin D status than other
      educational groups. This study showed that a high proportion of postmenopausal
      women living in Guilan province had vitamin D insufficiency. Vitamin D inadequacy
      was more common in urban areas and especially in the upper social class.
      Supplement use and national strategies to prevent vitamin D insufficiency are
      strongly needed in this community.

PMID- 21184381
TI  - A comparison of eating practices of independently living older adults in private
      residences and in senior retirement housing: a pilot study.
AB  - This study investigated eating-related habits and their importance in older
      people and compared those living in private residences with those in senior
      retirement community housing. A convenience sample of 58 seniors answered eating
      related items from the Self-maintenance Habits and Preferences in Elderly
      questionnaire (SHAPE). Meal location, companions, concurrent activities, portion
      size, and food variety differed between private and retirement housing for some
      meals, but the overall importance assigned to eating practices was similar. The
      meals themselves appeared to be more important than any specific socio
      environmental element. Eating practices associated with dinner were more
      important than those for the other meals.

PMID- 21184382
TI  - A nutritional status survey of older adults in long-term care in the Yazd
      province of Iran.
AB  - It is important to assess the nutritional status of older adults because of its
      role in ensuring health and quality of life and its association with functional
      status. The purpose of this study was to evaluate the nutritional status of an
      older adult population living in long-term care institutions in the Yazd province
      of Iran. Fifty elderly subjects were randomly selected from each of two long-term
      care institutions in Yazd. A 3-day food intake survey was conducted using the
      direct weighing method and anthropometric measurements for calculating body mass
      index (BMI) were also collected. Of the participants, 54% of women and 41% of men
      had a BMI less than 19.9 kg/m(2). The mean intakes of energy, protein, vitamins A
      and C, riboflavin, and niacin as well as the minerals calcium, phosphorus, and
      iron, were significantly less than Dietary Reference Intakes (DRIs) for both
      genders. Thiamin intake was more than adequate in both women and men. In our
      study, the majority of elderly subjects displayed a poor reported nutritional
      intake according to the DRIs. Our findings support the development of national
      nutrition plans for older adults living in long-term care institutions as an
      important necessity.

PMID- 21184384
TI  - Review of microsurgical posterior urethral reconstruction.
AB  - Posterior urethra reconstruction can be a challenging proposition for both
      patient and surgeon. The vast majority of urethras can be successfully
      reconstructed with either anastomosis or grafting. However, there are some
      patients who have recurrent urethral strictures that require more complex
      reconstruction. There is some speculation that microsurgical penile
      revascularization may allow subsequent graft reconstruction with lower stricture
      rates, but this is not yet proven. For the most tenacious urethral strictures,
      free tissue transfer may be required. The free radial forearm flap is well suited
      for urethral reconstruction, and the free anterolateral thigh flap may also have
      a role for these patients. This article will review urethral trauma and
      strictures and microsurgery's role in reconstruction of the posterior urethra.

PMID- 21184385
TI  - Reconstruction of pressure sores with perforator-based propeller flaps.
AB  - Perforator flaps have been successfully used for reconstruction of pressure
      sores. Although V-Y advancement flaps approximate debrided wound edges,
      perforator-based propeller flaps allow rotation of healthy tissue into the
      defect. Perforator-based propeller flaps were planned in 13 patients. Seven
      pressure sores were over the sacrum, five over the ischial tuberosity, and one on
      the tip of the scapula. Three patients were paraplegic, six were bedridden, and
      five were ambulatory. In three patients, no perforators were found. In 10
      patients, propeller flaps were transferred. In two patients, total flap necrosis
      occurred, which was reconstructed with local advancement flaps. In two cases, a
      wound dehiscence occurred and had to be revised. One hematoma required
      evacuation. No further complications were noted. No recurrence at the flap site
      occurred. Local perforator flaps allow closure of pressure sores without
      harvesting muscle. The propeller version has the added benefit of transferring
      tissue from a distant site, avoiding reapproximation of original wound edges.
      Twisting of the pedicle may cause torsion and venous obstruction. This can be
      avoided by dissecting a pedicle of at least 3 cm. Propeller flaps are a safe
      option for soft tissue reconstruction of pressure sores.

PMID- 21184386
TI  - [Acute appendicitis - changes in epidemiology, diagnosis and therapy].
AB  - Appendicitis is the most common cause of an -acute abdomen. Around 135 000
      patients undergo appendectomy in Germany every year. Acute -appendicitis shows
      changes in epidemiology, -diagnosis and therapy. Epidemiological data indicate a
      continuing decrease in the incidence of acute non-perforated appendicitis. The
      incidence of perforated appendicitis has remained constant despite laparoscopy
      and imaging diagnostics. The status of sonography and CT scanning is increasing
      in the diagnosis of appendicitis. But there are differences between the
      sensitivity and specifity of study results and the clinical routine. The in
      crease of imaging diagnostics does not correlate with a decrease in the incidence
      of perforated -appendicitis. Laparoscopic appendectomy has -developed as a
      dominant method for operative therapy. There is no proof of a higher rate of
      postoperative intraabdominal abscesses any more. The use of a stapler is mostly
      required for appendical stump closure.

PMID- 21184387
TI  - [Is age a risk factor for laparoscopic colorectal surgery?].
AB  - BACKGROUND: The aims of this study were to evaluate the results of laparoscopic
      colorectal surgery in elderly patients and compare them with the results of open
      procedures. METHODS: An analysis of a prospectively collected database of 705
      patients who underwent in the period between January 2001 and December 2006
      elective laparoscopic (LAC) or open (OC) colorectal surgery was performed. The
      primary end point was the morbidity rate, which was analysed in relation to the
      age (<= 75 years, > 75 years) and operative technique (laparoscopic, open).
      RESULTS: During the study period, 360 elective laparoscopic and 345 elective open
      colorectal operations were performed. 140 patients (20%) were older than 75 years
      (geriatrics), 60 of whom underwent laparoscopic and 80 open surgery. Both groups
      of patients (laparoscopic vs. open) were comparable in basic parameters. Mean
      operative time for laparoscopic colorectal resections was not longer (LAC 141 +/-
      46 min vs. OC 137 +/- 57 min, n. s.); even in cases of simple stoma formation it
      was significantly shorter (LAC 42 +/- 19 min vs. OC 78 +/- 32 min, p = 0.004). In
      the group of younger patients (<= 75 years) the open approach was associated with
      a statistically significant increase of postoperative morbidity (LAC 26% vs. OC
      34%, p = 0.039). In the group of geriatric patients (> 75 years) the open
      approach was associated with a significantly high incidence of postoperative
      morbidity (LAC 27% vs. OC 48%, p = 0.012) too. In the laparoscopically operated
      patients, the morbidity rate did not differ in both age groups (older than 75
      years 27% vs. younger than 75 years 26%, n. s.). Conversely, open procedures in
      elderly patients were associated with a significant increase of postoperative
      complications (morbidity) compared to younger patients (older than 75 years 48%
      vs. younger than 75 years 34%, p = 0.033). CONCLUSION: On account of the lower
      incidence of post-operative complications, the laparoscopic approach should be
      indicated in colorectal surgery for geriatric patients.

PMID- 21184388
TI  - [Introduction to adverse drug reactions and drug-drug interaction].
AB  - Adverse drug reactions are very common during a systemic drug therapy. Most of
      these are fortunately mild or moderate and transient. Serious adverse drug
      reactions often lead to hospitalisation. Drug-drug interactions can also
      contribute substantially to differences in drug response. Drug-induced inhibition
      of drug metabolising enzymes is usually competitive and causes an increased
      exposure of the drug whose metabolism is inhibited. This usually results in a
      higher incidence of adverse drug reactions and an increased severity. Conversely
      enzyme induction increases the metabolic capacity thereby reducing the exposure
      of a drug with sometimes loss of drug effects (nonresponse). Detailed knowledge
      of the causative mechanisms will help detecting and avoiding severe adverse drug
      reactions.

PMID- 21184389
TI  - [Drug-drug interactions and nephrotoxicity].
AB  - Nephrotoxicity is a common and often clinically relevant adverse drug reaction.
      Mechanisms include vascular, tubulo-toxic, tubulo-obstructive, and immunological
      effects. Drug-drug interactions may occur at a pharmacokinetic or pharmacodynamic
      level. Such interactions can both increase (cisplatin and aminoglycoside) but
      also protect from nephrotoxicity (cidofovir and probenecid).Important measures
      for preventing nephrotoxicity are (1) consideration of potential pharmacokinetic
      and pharmacodynamic interactions when prescribing a drug, (2) prescription of
      nephrotoxic drugs for the shortest possible period, (3) detection of high-risk
      patients, and (4) consideration of hydration and prophylactic comedication.

PMID- 21184390
TI  - [Adverse drug reactions and drug interactions in analgesic therapy].
AB  - Nowadays multiple pharmacotherapeutic options are available to treat pain. The
      diverse analgesics differ not only in their mechanism, potency, and efficacy but
      vary also in adverse drug reactions and drug interactions. Knowledge about the
      clinically relevant aspects in this field is essential to fit pain therapy to the
      individual patient. Non-opioids such as acetaminophen are hepatotoxic at high
      doses or may induce agranolcytosis such as dipyrone. Non-steroidal anti
      inflammatory drugs (e.g. diclofenac) have a high risk of toxic effects
      particularly affecting stomach and kidneys. Especially the reasonable combination
      with other drugs that were frequently used in pain therapy, such as
      glucocorticoids, can induce gastrointestinal toxicity and bleeding. Also the use
      of WHO-II opioids (e.g. tramadol) should be carefully monitored for drug-related
      problems because of their individual drug metabolism and multiple drug-drug
      interactions. WHO-II as well as WHO-III opioids (e.g. morphine) provoke
      constipation, nausea, vomiting, and flush as adverse drug reactions of particular
      clinical relevance. An appropriate supportive therapy is mandatory, particularly
      regarding laxatives.

PMID- 21184391
TI  - [Delirium induced by drug treatment].
AB  - Delirium may be induced by a variety of reasons, among them drugs and in
      particular the combination of drugs. In elderly people a delirium is often
      misinterpreted as dementia. Anticholinergic activity is the mode of action by
      which drugs cause delirium. Antipsychotic drugs, antidepressants, antihistamines,
      and of course anticholinergic drugs themselves are the major anticholinergic
      classes of drugs. In addition some opioids have anticholinergic effects. Other
      drugs may induce delirium by dehydration (loop diuretics like furosemide) or
      sedation (benzodiazapines like lorazepam). Elderly people are at especially high
      risk to develop delirium, because of the multitude of drugs often prescribed to
      them, because they tend to drink to little, and because their brain is more
      sensitive to psychoactive drugs.

PMID- 21184392
TI  - [Adverse drug reactions in children].
AB  - Adverse drug reactions (ADRs) are important safety issues in pediatric
      pharmacotherapy because they can lead to significant morbidity and mortality in
      this population. It is currently assumed that the incidence of ADRs in children
      is between 0.6 % and 19.9 % and that between 0.6 % und 6 % of all hospital
      admissions of children are triggered by ADRs. Underreporting and insufficient
      documentation of ADRs in children, however, may obstruct the view on the true
      numbers. Pharmacovigilance centres in some countries are under way to increase
      the awareness of the problem. Their programs may help to systematically improve
      reporting and documentation of ADRs. One important goal is to better assess
      causality between the patients clinical reaction and drug use, because this is
      the key knowledge to specifically target an effective and safe pharmacotherapy.

PMID- 21184394
TI  - [Adverse drug reactions and interactions - cause of admission to hospital and
      after discharge].
AB  - Adverse drug reactions (ADRs) and interactions not only cause hospitalisation but
      also occur during the hospital stay itself. There, they contribute significantly
      to patient morbidity and mortality and furthermore create considerable additional
      costs for the healthcare systems. The majority of ADRs are dose-dependent and
      commonly found also for long-established and well known drugs. This is inherently
      related to the drug's mode of action. Accordingly, even rare side effects like
      rhabdomyolysis or arrhythmia turn out to be the limiting factor in the use of
      certain drugs which may even result in their withdrawal from the market.
      Detection and analysis of ADRs directly in the hospitals is therefore highly
      important. This provides a unique opportunity to investigate serious cases
      leading to hospitalisation, and, also prevent further occurrence of ADRs after
      discharge from hospital and thus enhance the protection of the patients.
      Clinically most relevant interactions have been found for drug metabolizing
      enzymes (e.g. CYP3A4, 1A2, 2D6), and drug efflux transporters (e.g. P
      glycoprotein). Data based drug-interaction software is an important tool for
      physicians to either reduce ADRs or to select alternatives with lower interaction
      potential.

PMID- 21184393
TI  - [Pruritus - an important adverse drug reaction].
AB  - Chronic pruritus may be induced by drugs. In this, chronic pruritus must be
      differentiated from acute pruritus. Acute pruritus can appear as a side-effect of
      a medication as for example antibiotics and will usually disappear within some
      days after discontinuation of the drug. Chronic pruritus is defined as itch
      sensations lasting longer than six weeks. Chronic pruritus, however, forms a
      major challenge in diagnostic and therapeutic respect. In view of the demographic
      development of the population and the frequent polypharmacy especially in the
      elderly, drugs should always be considered as a possible cause for pruritus.

PMID- 21184395
TI  - [Herbal drug-drug interaction and adverse drug reactions].
AB  - Herbal medicines are used by many patients. Their known or potential adverse
      events should be taken into account during treatment with herbal medicines. In
      this article adverse effects of commonly used herbs are presented. St. John's
      wort is known to be a potent inducer of cytochrome P450 (CYP) 3A4 leading to
      reduced blood concentrations of a number of CYP3A4 substrates. For many other
      combinations evidence is sparse but due to a number of case reports of adverse
      interactions they should only cautiously be combined with certain critical dose
      drugs until their risk is fully assessed. Pertinent examples are the
      immunostimulant Echinacea which could decrease the effect of immunosuppressants.
      Ginseng and ginkgo should not be combined with anticoagulants. Excessive sedation
      may occur with concomitant use of valerian and barbiturates.

PMID- 21184397
TI  - Structural variability of endotoxins from R-type isogenic mutants of Shigella
      sonnei.
AB  - The structural variations in the rough-type endotoxins [lipopolysaccharides
      (LPSs)] of Shigella sonnei mutant strains (S. sonnei phase II-4303, R41, 562H and
      4350) were investigated by Matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF-MS) and tandem MS. A series of S. sonnei
      mutants had previously been the subject of analytical studies on the biosynthesis
      of heptose components in the core oligosaccharide region of LPSs. This study
      gives a complete overview on the structures of the full core and lipid A of S.
      sonnei mutant strains by MS. We found that the LPSs of the isogenic rough mutants
      were formed in a step-like manner containing 0:1:2:3 heptose in the deep core
      region of 4350, 562H, R41 and 4303, respectively, and the longest LPS from the
      mutant S. sonnei 4303 contained also five hexoses. The structural variations in
      the lipid A moiety and in the oligosaccharide part of the intact LPS were
      followed by MALDI-TOF-MS/MS. For the dissolution and the ionization of the
      samples, 2,5-dihydroxybenzoic acid in citric acid solution was applied as matrix.
      The detailed evaluation of the mass spectra indicates heterogeneity in the lipid
      part due to the differences in the phosphate and fatty acid composition.

PMID- 21184398
TI  - A fully validated method for the determination of vardenafil in blood using gas
      chromatography/mass spectrometry.
AB  - Vardenafil (VDN) is one of the three commercially available phosphodiesterase
      type 5 inhibitors and it is mainly used in the treatment of erectile dysfunction.
      A sensitive and specific gas chromatography/mass spectrometry (GC/MS) method for
      the determination of VDN in blood has been developed and validated. Sample
      preparation included solid-phase extraction and derivatization with N-methyl-N
      tert-butyldimethylsilyl-trifluoroacetamide (MTBSTFA) and 1% tert
      butyldimethylsilylchloride (TBDMSCl). Protriptyline was used as the internal
      standard for this assay. Limits of detection and quantification for VDN were 0.70
      and 2.00 ug/l, respectively. The calibration curves were linear within the
      dynamic range 2.00-200.0 ug/l with a correlation coefficient higher than 0.991.
      Absolute recovery ranged from 88.6% to 95.7% for the analyte of interest at three
      quality control levels. Intra- and inter-day accuracy was found to be between -
      6.1% to 10.8% and - 9.3% to 11.6%, respectively, whereas intra- and inter-day
      precision was < 7.8% and 9.7%, correspondingly. The proposed method is the first
      fully validated GC/MS method for the determination of VDN in blood samples and it
      can be used in routine every day analysis by clinical and forensic laboratories
      for pharmacokinetic studies, for therapeutic drug level monitoring or for the
      investigation of related forensic cases. A few blood samples analyzed using the
      developed method is reported herein to demonstrate the suitability of the method.

PMID- 21184400
TI  - Chemical control of stem cell fate and developmental potential.
AB  - Potential applications of stem cells in medicine range from their inclusion in
      disease modeling and drug discovery to cell transplantation and regenerative
      therapies. However, before this promise can be realized several obstacles must be
      overcome, including the control of stem cell differentiation, allogeneic
      rejection and limited cell availability. This will require an improved
      understanding of the mechanisms that govern stem cell potential and the
      development of robust methods to efficiently control their fate. Recently, a
      number of small molecules have been identified that can be used both in vitro and
      in vivo as tools to expand stem cells, direct their differentiation, or reprogram
      somatic cells to a more naive state. These molecules have provided a wealth of
      insights into the signaling and epigenetic mechanisms that regulate stem cell
      biology, and are already beginning to contribute to the development of effective
      treatments for tissue repair and regeneration.

PMID- 21184404
TI  - Self-immobilizing fluorogenic imaging agents of enzyme activity.

PMID- 21184412
TI  - 50 years of the International Edition: more substance than appearance.

PMID- 21184410
TI  - Systematic investigation of halogen bonding in protein-ligand interactions.

PMID- 21184413
TI  - K. Peter C. Vollhardt.

PMID- 21184434
TI  - Observations of different core water cluster ions Y-(H2O)n (Y = O2, HOx, NOx,
      COx) and magic number in atmospheric pressure negative corona discharge mass
      spectrometry.
AB  - Reliable mass spectrometry data from large water clusters Y(-)(H(2)O)(n) with
      various negative core ions Y(-) such as O(2)(-), HO(-), HO(2)(-), NO(2)(-),
      NO(3)(-), NO(3)(-)(HNO(3))(2), CO(3)(-) and HCO(4)(-) have been obtained using
      atmospheric pressure negative corona discharge mass spectrometry. All the core Y(
      ) ions observed were ionic species that play a central role in tropospheric ion
      chemistry. These mass spectra exhibited discontinuities in ion peak intensity at
      certain size clusters Y(-)(H(2)O)(m) indicating specific thermochemical
      stability. Thus, Y(-)(H(2)O)(m) may correspond to the magic number or first
      hydrated shell in the cluster series Y(-)(H(2)O)(n). The high intensity
      discontinuity at HO(-)(H(2)O)(3) observed was the first mass spectrometric
      evidence for the specific stability of HO(-)(H(2)O)(3) as the first hydrated
      shell which Eigen postulated in 1964. The negative ion water clusters Y(
      )(H(2)O)(n) observed in the mass spectra are most likely to be formed via core
      ion formation in the ambient discharge area (760 torr) and the growth of water
      clusters by adiabatic expansion in the vacuum region of the mass spectrometers
      (~1 torr). The detailed mechanism of the formation of the different core water
      cluster ions Y(-)(H(2)O)(n) is described.

PMID- 21184435
TI  - Tautomerization in gas-phase ion chemistry of isomeric C-8 deoxyguanosine adducts
      from phenol-induced DNA damage.
AB  - Collision-induced dissociation (CID) of 8-(4''-hydroxyphenyl)-2'-deoxyguanosine
      and 8-(2''-hydroxyphenyl)-2'-deoxyguanosine was investigated using sequential
      tandem mass spectrometry. These adducts represent biomarkers of DNA damage linked
      to phenolic radicals and were investigated to gain insight into the effects of
      chemical structure of a C-8 modification on fragmentation pathways of modified 2'
      deoxyguanosine (dG). CID in MS(2) of the deprotonated molecules of both the
      isomers generated the same product ion having the same m/z values. CID in MS(3)
      of the product ion at m/z 242 and CID in MS(4) experiments carried out on the
      selected product ions at m/z 225 and m/z 218 afford distinct fragmentation
      patterns. The conformational properties of isomeric product ions from CID showed
      that the ortho-isomers possess the unique ability to tautomerize through an
      intramolecular proton transfer between the phenolic OH group and the imine
      nitrogen (N7). Tautomerization of ortho-isomers to their keto-tautomers led to
      differences in their system of conjugated double bonds compared with either their
      enol-tautomer or the para-isomer. The charge redistribution through the N-7 site
      on the imidazole ring is a critical step in guanosine adduct fragmentation which
      is disrupted by the formation of the keto-tautomer. For this reason, different
      reaction pathways are observed for 8-(4''-hydroxyphenyl)-2'-deoxyguanosine and 8
      (2''-hydroxyphenyl)-2'-deoxyguanosine. We present herein the dissociation and the
      gas-phase ion-molecule reactions for highly conjugated ions involved in the CID
      ion chemistry of the investigated adducts. These will be useful for those using
      tandem mass spectrometry for structural elucidation of C-8 modified dG adducts.
      This study demonstrates that the modification at the C-8 site of dG has the
      potential to significantly alter the reactivity of adducts. We also show the
      ability of tandem mass spectrometry to completely differentiate between the
      isomeric dG adducts investigated.

PMID- 21184437
TI  - Frequency and predictors of proxy-confirmed post-stroke cognitive complaints in
      lacunar stroke patients without major depression.
AB  - OBJECTIVE: Many lacunar stroke patients complained of cognitive decline after
      stroke. This study aims to investigate the factors underlying post-stroke
      cognitive complaints in these patients. METHODS: Seventy-five consecutive lacunar
      stroke patients without major depression were recruited for the study. Stroke
      severity was measured using NIHSS score and MRI was performed during the acute
      admission period. At 3 months, objective psychometric performance and depressive
      symptoms were assessed. Post-stroke cognitive complaints were corroborated by a
      proxy. Using logistic regression we examined the contribution of demographic
      features, stroke severity, objective psychometric scores, depressive symptoms,
      and imaging features (white matter lesion volume and infarct measures) to post
      stroke cognitive complaints. RESULTS: Thirty-two (42.7%) patients had post-stroke
      cognitive complaints. Patients with post-stroke cognitive complaints had more
      depressive symptoms and worse psychometric performance than those without. In the
      multivariate logistic regression model, only the severity of depressive symptoms
      was independently associated with post-stroke cognitive complaints. CONCLUSIONS:
      This study suggests that post-stroke cognitive complaints are frequent among
      lacunar stroke patients without major depression and are prominently determined
      by the subclinical depressive symptomatology.

PMID- 21184438
TI  - Heterologous production of polyunsaturated fatty acids in Saccharomyces
      cerevisiae causes a global transcriptional response resulting in reduced
      proteasomal activity and increased oxidative stress.
AB  - Due to their health benefits there is much interest in developing microbial
      processes for efficient production of polyunsaturated fatty acids (PUFAs). In
      this study we co-expressed Mucor rouxii Delta(12) - and Delta(6) -desaturase
      genes in Saccharomyces cerevisiae, which resulted in a yeast strain that
      accumulated linoleic acid and gamma-linolenic acid in the different lipid
      species. Additionally, the strain contained higher levels of phospholipids and
      lower levels of ergosterol than the reference strain. Integrated analysis of the
      transcriptome revealed decreased expression of genes involved in ergosterol
      biosynthesis, but more unexpectedly it also pointed towards attenuated activity
      of the ubiquitin-proteasome system and a reduced oxidative stress response. In
      vitro and in vivo measurements showed reduced levels of all three proteasomal
      activities and also increased levels of reactive oxidative species in the PUFA
      producing strain. Overall our results clearly show that PUFAs in yeast can be
      detrimental for several key cellular pathways, such as the oxidative stress
      response and proteasomal activity, suggesting that the membrane composition is of
      vital importance for these processes.

PMID- 21184439
TI  - Screening of cellulases for biofuel production: online monitoring of the
      enzymatic hydrolysis of insoluble cellulose using high-throughput scattered light
      detection.
AB  - A new prospective cellulase assay simultaneously combining high-throughput,
      online analysis and insoluble cellulosic substrates is described. The hydrolysis
      of three different insoluble cellulosic substrates, catalysed by a commercial
      cellulase preparation from Trichoderma reesei (Celluclast), was monitored using
      the BioLector - allowing online monitoring of scattered light intensities in a
      continuously shaken microtiter plate. Cellulase activities could be
      quantitatively assayed using the BioLector. At low cellulase/cellulose ratios,
      the Michaelis-Menten parameters of the cellulase mixture were mainly affected by
      the crystallinity index of the cellulose. Here, the apparent maximum cellulase
      activities inversely correlated with the crystallinity index of the cellulose. At
      high cellulase/cellulose ratios the particle size of the cellulose, defining the
      external surface area accessible to the cellulases, was the key determining
      factor for cellulase activity. The developed technique was also successfully
      applied to evaluate the pH optimum of cellulases. Moreover, the non-hydrolytic
      deagglomeration of cellulose particles was investigated, for the first time,
      using high-throughput scattered light detection. In conclusion, this cellulase
      assay ideally links high-throughput, online analysis and realistic insoluble
      cellulosic substrates in one simple system. It will considerably simplify and
      accelerate fundamental research on cellulase screening.

PMID- 21184470
TI  - Integrating DNA barcode data and taxonomic practice: determination, discovery,
      and description.
AB  - DNA barcodes, like traditional sources of taxonomic information, are potentially
      powerful heuristics in the identification of described species but require
      mindful analytical interpretation. The role of DNA barcoding in generating
      hypotheses of new taxa in need of formal taxonomic treatment is discussed, and it
      is emphasized that the recursive process of character evaluation is both
      necessary and best served by understanding the empirical mechanics of the
      discovery process. These undertakings carry enormous ramifications not only for
      the translation of DNA sequence data into taxonomic information but also for our
      comprehension of the magnitude of species diversity and its disappearance. This
      paper examines the potential strengths and pitfalls of integrating DNA sequence
      data, specifically in the form of DNA barcodes as they are currently generated
      and analyzed, with taxonomic practice.

PMID- 21184472
TI  - Multiple unknown degradants generated from the insect repellent DEET by
      photoinduced processes on TiO2.
AB  - This paper deals with the photocatalytic transformation of N,N-diethyl-m
      toluamide (DEET), one of the most widespread and efficient mosquito repellents,
      under simulated solar irradiation using titanium dioxide as the photocatalytic
      source of oxidizing species. The investigation involved monitoring of the DEET
      decomposition, the identification of intermediate compounds and the assessment of
      mineralization. High-resolution mass spectrometry was employed to assess the
      evolution of the photocatalyzed process over time. Fifty-one main species were
      identified after DEET transformation. Several isomeric species were formed and
      were characterized by analyzing MS and MS(n) spectra in full, and by comparison
      with parent molecule fragmentation pathways. In the DEET molecule, the initial
      transformation involved mono- and polyhydroxylation followed by oxidation of the
      alcohol groups, cleavage of the alkyl chains or ring opening. All these
      intermediates are easily degraded and DEET is completely mineralized after 4 h of
      irradiation. Microtox bioassay (Vibrio fischeri) was employed to evaluate the
      ecotoxicity of solutions treated by photocatalysis.

PMID- 21184481
TI  - The transcriptional response to chronic stress and glucocorticoid receptor
      blockade in the hippocampal dentate gyrus.
AB  - The dentate gyrus (DG) of the hippocampus plays a crucial role in learning and
      memory. This subregion is unique in its ability to generate new neurons
      throughout life and integrate these new neurons into the hippocampal circuitry.
      Neurogenesis has further been implicated in hippocampal plasticity and
      depression. Exposure to chronic stress affects DG function and morphology and
      suppresses neurogenesis and long-term potentiation (LTP) with consequences for
      cognition. Previous studies demonstrated that glucocorticoid receptor (GR)
      blockade by a brief treatment with the GR antagonist mifepristone (RU486) rapidly
      reverses the stress and glucocorticoid effects on neurogenesis. The molecular
      pathways underlying both the stress-induced effects and the RU486 effects on the
      DG are, however, largely unknown. The aim of this study was therefore (1) to
      investigate by microarray analysis which genes and pathways in the DG are
      sensitive to chronic stress and (2) to investigate to what extent blockade of GR
      can normalize these stress-induced effects on DG gene expression. Chronic stress
      exposure affected the expression of 90 genes in the DG (P < 0.01), with an
      overrepresentation of genes involved in brain development and morphogenesis and
      synaptic transmission. RU486 treatment of stressed animals affected expression of
      107 genes; however, mostly different genes than those responding to stress.
      Interestingly, we found CREBBP to be normalized by RU486 treatment to levels
      observed in control animals, suggesting that CREB-signaling may play a central
      role in mediating the chronic stress effects on neurogenesis, LTP and calcium
      currents. The identified genetic pathways provide insight into the stress-induced
      adaptive plasticity of the hippocampal DG that is so central in learning and
      memory and will direct future studies on the functional outcome and modulation of
      these stress effects.

PMID- 21184485
TI  - Beta-peptoid "foldamers"--why the additional methylene unit?
AB  - The field of peptoid (i.e., N-alkylglycine) research has been thriving since the
      first publications on this molecular design appeared in 1992. A highly efficient
      and modular synthetic platform, which is compatible with automation and ready
      generation of combinatorial libraries, was published the same year. This has
      enabled the investigation of numerous compounds with this architecture, and
      ligands with a wide variety of interesting biological targets have thus been
      discovered. Furthermore, detailed biophysical and structural studies focusing on
      the investigation of the conformational space adopted and three-dimensional
      folding of these peptide mimics have been undertaken. The same is true for beta
      peptides (i.e., oligomers composed of beta-amino acids). Since the first
      publication describing peptide mimics combining these two structural
      modifications [the N-alkyl-beta-alanines (beta-peptoids)] in 1998, on the other
      hand, the application of this backbone construct has appeared much more sparsely
      in the literature. The present perspective article will provide an overview of
      the data obtained for beta-peptoid-containing peptide mimics as well as a
      discussion of the future challenges associated with this type of backbone
      modification.

PMID- 21184486
TI  - Peptoid origins.
AB  - Peptoid oligomers were initially developed as part of a larger basic research
      effort to accelerate the drug-discovery process in the biotech/biopharma
      industry. Their ease of synthesis, stability, and structural similarity to
      polypeptides made them ideal candidates for the combinatorial discovery of novel
      peptidomimetic drug candidates. Diverse libraries of short peptoid oligomers
      provided one of the first demonstrations in the mid-1990s that high-affinity
      ligands to pharmaceutically relevant receptors could be discovered from
      combinatorial libraries of synthetic compounds. The solid-phase submonomer method
      of peptoid synthesis was so efficient and general that it soon became possible to
      explore the properties of longer polypeptoid chains in a variety of areas beyond
      drug discovery (e.g., diagnostics, drug delivery, and materials science).
      Exploration into protein-mimetic materials soon followed, with the fundamental
      goal of folding a non-natural sequence-specific heteropolymer into defined
      secondary or tertiary structures. This effort first yielded the peptoid helix and
      much later the peptoid sheet, both of which are secondary-structure mimetics that
      are close relatives to their natural counterparts. These crucial discoveries have
      brought us closer to building proteinlike structure and function from a non
      natural polymer and have provided great insight into the rules governing polymer
      and protein folding. The accessibility of peptoid synthesis to chemists and
      nonchemists alike, along with a lack of information-rich non-natural polymers
      available to study, has led to a rapid growth in the field of peptoid science by
      many new investigators. This work provides an overview of the initial discovery
      and early developments in the peptoid field.

PMID- 21184487
TI  - Peptoid conformational free energy landscapes from implicit-solvent molecular
      simulations in AMBER.
AB  - To test the accuracy of existing AMBER force field models in predicting peptoid
      conformation and dynamics, we simulated a set of model peptoid molecules recently
      examined by Butterfoss et al. (JACS 2009, 131, 16798-16807) using QM methods as
      well as three peptoid sequences with experimentally determined structures. We
      found that AMBER force fields, when used with a Generalized Born/Surface Area
      (GBSA) implicit solvation model, could accurately reproduce the peptoid torsional
      landscape as well as the major conformers of known peptoid structures. Enhanced
      sampling by replica exchange molecular dynamics (REMD) using temperatures from
      300 to 800 K was used to sample over cis-trans isomerization barriers. Compared
      to (Nrch)5 and cyclo-octasarcosyl, the free energy of N-(2-nitro-3-hydroxyl
      phenyl)glycine-N-(phenyl)glycine has the most "foldable" free energy landscape,
      due to deep trans-amide minima dictated by N-aryl sidechains. For peptoids with
      (S)-N (1-phenylethyl) (Nspe) side chains, we observe a discrepancy in backbone
      dihedral propensities between molecular simulations and QM calculations, which
      may be due to force field effects or the inability to capture n --> n*
      interactions. For these residues, an empirical phi-angle biasing potential can
      "rescue" the backbone propensities seen in QM. This approach can serve as a
      general strategy for addressing force fields without resorting to a complete
      reparameterization. Overall, this study demonstrates the utility of implicit
      solvent REMD simulations for efficient sampling to predict peptoid conformational
      landscapes, providing a potential tool for first-principles design of sequences
      with specific folding properties.

PMID- 21184489
TI  - DNA and chromatin imaging with super-resolution fluorescence microscopy based on
      single-molecule localization.
AB  - With the expansion of super-resolution fluorescence microscopy methods, it is now
      possible to access the organization of cells and materials at the nanoscale by
      optical means. This review discusses recent progress in super-resolution imaging
      of isolated and cell DNA using single-molecule localization methods. A high
      labeling density of photoswitchable fluorophores is crucial for these techniques,
      which can be provided by sequence independent DNA stains in which photoblinking
      reactions can be induced. In particular, unsymmetrical cyanine intercalating dyes
      in combination with special buffers can be used to image isolated DNA with a
      spatial resolution of 30-40 nm. For super-resolution imaging of chromatin, cell
      permeant cyanine dyes that bind the minor groove of DNA have the potential to
      become a useful alternative to the labeling of histones and other DNA-associated
      proteins. Other recent developments that are interesting in this context such as
      high density labeling methods or new DNA probes with photoswitching
      functionalities are also surveyed. Progress in labeling, optics, and single
      molecule localization algorithms is being rapid, and it is likely to provide real
      insight into DNA structuring in cells and materials.

PMID- 21184526
TI  - An evaluation of biotic ligand models predicting acute copper toxicity to Daphnia
      magna in wastewater effluent.
AB  - The toxicity of Cu to Daphnia magna was investigated in a series of 48-h
      immobilization assays in effluents from four wastewater treatment works. The
      assay results were compared with median effective concentration (EC50) forecasts
      produced by the HydroQual biotic ligand model (BLM), the refined D. magna BLM,
      and a modified BLM that was constructed by integrating the refined D. magna
      biotic ligand characterization with the Windermere humic aqueous model (WHAM) VI
      geochemical speciation model, which also accommodated additional effluent
      characteristics as model inputs. The results demonstrated that all the BLMs were
      capable of predicting toxicity by within a factor of two, and that the modified
      BLM produced the most accurate toxicity forecasts. The refined D. magna BLM
      offered the most robust assessment of toxicity in that it was not reliant on the
      inclusion of effluent characteristics or optimization of the dissolved organic
      carbon active fraction to produce forecasts that were accurate by within a factor
      of two. The results also suggested that the biotic ligand stability constant for
      Na may be a poor approximation of the mechanisms governing the influence of Na
      where concentrations exceed the range within which the biotic ligand stability
      constant value had been determined. These findings support the use of BLMs for
      the establishment of site-specific water quality standards in waters that contain
      a substantial amount of wastewater effluent, but reinforces the need for
      regulators to scrutinize the composition of models, their thermodynamic and
      biotic ligand parameters, and the limitations of those parameters.

PMID- 21184527
TI  - The effect of fullerenes and functionalized fullerenes on Daphnia magna
      phototaxis and swimming behavior.
AB  - The effects of carbon fullerenes (C(60) ) on the environment is a growing concern
      as the use of nanotechnology continues to increase. Previous studies have
      reported alteration in Daphnia magna behavior, including increased hopping
      frequency, heart rate, and appendage movement in response to tetrahydrofuran
      solubilized C(60) and increased hopping rate and appendage movement in response
      to tetrahydrofuran-solubilized C(60) HxC(70) Hx exposure. The objective of the
      current study was to evaluate effects of water-stirred C(60) and sonicated
      carboxylic acid functionalized fullerenes (fC(60) ) on D. magna behavior.
      Behavioral endpoints are important because changes in behavior can influence
      predator avoidance behaviors, alter predation risk, and potentially lead to
      population-level effects in D. magna. To evaluate the potential effect of
      fullerenes on phototactic behavior, D. magna were exposed to 545.4 ug/L C(60) and
      545.6 ug/L fC(60) , and vertical position was monitored. Daphnia magna were also
      exposed to 545.4 ug/L C(60) , 545.6 ug/L fC(60) , and 829.3 ug/L fC(60) , and
      swimming movements were recorded. Fullerenes altered the vertical migration
      response of D. magna to the addition of food, but D. magna vertical position
      response to predator cues was similar for fullerenes and controls. In addition,
      D. magna reduced swimming speed when exposed to C(60) , but other components of
      D. magna swimming behavior were not affected. This research supports previous
      findings and suggests that C(60) may influence D. magna behavior and highlights
      the need for further research on sublethal behavioral modifications in aquatic
      organisms in response to nanomaterials.

PMID- 21184528
TI  - Perfluorooctane sulfonic acid exposure increases cadmium toxicity in early life
      stage of zebrafish, Danio rerio.
AB  - Exposure to perfluorooctane sulfonic acid (PFOS) is known to induce thyroid
      related adverse effects in aquatic organisms. Because an antioxidant defense
      mechanism is one of the key functions of the thyroid gland, we examined whether
      preexposure to PFOS could disrupt thyroid function and enhance cadmium (Cd)
      induced oxidative stress in fish. Zebrafish embryos were exposed to control or
      0.5 mg/L PFOS for 7 d after fertilization and subsequently exposed to 0.038 mg/L
      of Cd(2+) or a mixture of the PFOS and Cd for an additional 3 d until 10 d
      postfertilization (dpf). Survival rates, body length, messenger RNA (mRNA)
      expressions related to thyroid function and oxidative stress, the levels of
      thyroid hormones, and malondialdehyde and antioxidant enzyme activities were
      measured. Significant down-regulation of mRNAs related to thyroid function
      (thyroid hormone receptor-alpha [THRalpha], thyroid hormone receptor-beta
      [THRbeta], hematopoietically expressed homeobox [hhex], and paired box gene 8
      [pax8]) and decrease of throxine (T4) levels were observed in the PFOS
      preexposure group, suggesting that PFOS preexposure would influence the
      performance of thyroid gland in the later stages of life. Certain genes relative
      to oxidative stress, such as superoxide dismutase 1 (sod1) and heat shock protein
      70 (hsp70), in the PFOS preexposure group were significantly up-regulated when
      the larvae were subsequently exposed to Cd or to the mixture of PFOS and Cd.
      Glutathione S-transferase activity and malondialdehyde levels of the PFOS
      preexposed group were increased significantly by Cd exposure. Significant
      decrease of the survival rates and body length of fish were observed at 10 dpf
      among the larvae that were previously exposed to PFOS. These results suggest that
      preexposure to PFOS could affect antioxidant defense mechanisms and potentially
      increase the toxicity of Cd on mRNA expression and enzyme activity level
      responses, as well as on survival or growth of individuals.

PMID- 21184529
TI  - Toxicity of water-soluble fractions of biodiesel fuels derived from castor oil,
      palm oil, and waste cooking oil.
AB  - Concerns over the sustained availability of fossil fuels and their impact on
      global warming and pollution have led to the search for fuels from renewable
      sources to address worldwide rising energy demands. Biodiesel is emerging as one
      of the possible solutions for the transport sector. It shows comparable engine
      performance to that of conventional diesel fuel, while reducing greenhouse gas
      emissions. However, the toxicity of products and effluents from the biodiesel
      industry has not yet been sufficiently investigated. Brazil has a very high
      potential as a biodiesel producer, in view of its climatic conditions and vast
      areas for cropland, with consequent environmental risks because of possible
      accidental biodiesel spillages into water bodies and runoff to coastal areas.
      This research determined the toxicity to two marine organisms of the water
      soluble fractions (WSF) of three different biodiesel fuels obtained by methanol
      transesterification of castor oil (CO), palm oil (PO), and waste cooking oil
      (WCO). Microalgae and sea urchins were used as the test organisms, respectively,
      for culture-growth-inhibition and early-life-stage-toxicity tests. The toxicity
      levels of the analyzed biodiesel WSF showed the highest toxicity for the CO,
      followed by WCO and the PO. Methanol was the most prominent contaminant;
      concentrations increased over time in WSF samples stored up to 120 d.

PMID- 21184530
TI  - Impact of nano titanium dioxide exposure on cellular structure of Anabaena
      variabilis and evidence of internalization.
AB  - The present study investigated the impact of nano titanium dioxide (nTiO(2) )
      exposure on the cellular structures of the nitrogen-fixing cyanobacteria Anabaena
      variabilis. Results of the present study showed that nTiO(2) exposure led to
      observable alteration in various intracellular structures and induced a series of
      recognized stress responses, including production of reactive oxygen species
      (ROS), appearance and increase in the abundance of membrane crystalline
      inclusions, membrane mucilage layer formation, opening of intrathylakoidal
      spaces, and internal plasma membrane disruption. The production of total ROS in
      A. variabilis cells increased with increasing nTiO(2) doses and exposure time,
      and the intracellular ROS contributed to only a small fraction (<10%) of the
      total ROS measured. The percentage of cells with loss of thylakoids and growth of
      membrane crystalline inclusions increased as the nTiO(2) dose and exposure time
      increased compared with controls, suggesting their possible roles in stress
      response to nTiO(2) , as previously shown for metals. Algal cell surface
      morphology and mechanical properties were modified by nTiO(2) exposure, as
      indicated by the increase in cell surface roughness and shifts in cell spring
      constant determined by atomic force microscopy analysis. The change in cell
      surface structure and increase in the cellular turgor pressure likely resulted
      from the structural membrane damage mediated by the ROS production. Transmission
      electron microscopy (TEM) analysis of nTiO(2) aggregates size distribution seems
      to suggest possible disaggregation of nTiO(2) aggregates when in close contact
      with microbial cells, potentially as a result of biomolecules such as DNA
      excreted by organisms that may serve as a biodispersant. The present study also
      showed, for the first time, with both TEM and Raman imaging that internalization
      of nTiO(2) particles through multilayered membranes in algal cells is possible.
      Environ. Toxicol. Chem. 2011; 30:861-869. (c) 2010 SETAC.

PMID- 21184531
TI  - Tissue-specific toxicological effects of cadmium in green mussels (Perna
      viridis): nuclear magnetic resonance-based metabolomics study.
AB  - Toxicity tests for metals have traditionally focused on selected biomarkers to
      characterize the biological stress induced by metals in marine organisms. Here
      nuclear magnetic resonance (NMR)-based metabolomics, a system biology tool, was
      applied to the marine green mussel, Perna viridis, to investigate the
      toxicological effects of Cd in both digestive gland and adductor muscle tissues.
      After Cd exposure for either two or four weeks, there was no significant
      metabolic change in the mussels exposed to Cd at 2 ug/L. At 20 ug/L, there were
      major metabolite changes related to amino acids, osmolytes, and energy
      metabolites. Digestive gland tissue was more sensitive to Cd than adductor muscle
      tissue. The adductor muscle tissue showed elevated levels of glutamine,
      glutamate, and lactate, and reduced levels of branched chain amino acids,
      aspartate, phenylalanine, and tyrosine. Overall, four weeks of Cd exposure
      produced neurotoxicity and metabolic disturbances and disturbed osmoregulation.
      These results suggest that the adductor muscle tissue of mussels may be a
      suitable supplemental biomarker for exposure to toxicants. In addition, the
      results demonstrate that (1) H-NMR-based metabolomic analysis can provide a
      systematic view of the toxicological effects of metals on mussels, suggesting
      that it might be employed to investigate the toxicological effects of other
      marine pollutants.

PMID- 21184532
TI  - Matrix effect study in the determination of linear alkylbenzene sulfonates in
      sewage sludge samples.
AB  - We propose a study of the matrix effect in the determination of linear
      alkylbenzene sulfonates (LAS) in sewage sludge samples. First, a rapid, selective
      and sensitive method is proposed. The method involves two stages: the extraction
      of the compound from the samples and analysis by liquid chromatography with
      fluorescence detection (LC-FLD). Three different techniques of extraction
      (microwave-assisted extraction, Soxhlet, and ultrasounds) were compared, and
      microwave-assisted extraction was selected as the best suited for our purpose.
      Microwave-assisted extraction allows reducing the extraction time (25 min
      compared with 12 h for conventional Soxhlet extraction) and solvent waste (25 ml
      of methanol compared with 200 ml for Soxhlet or more than 50 ml for the
      ultrasonic procedure). Absence of matrix effect was evaluated with two standards
      (2OC(8:0) and 2OC(16:0) ) that are not commercial; therefore, neither of them was
      detected in sewage sludge samples and they showed similar environmental behavior
      (adsorption and precipitation) to LAS (C(11:0) -C(13.0) ), which allow us to
      evaluate the matrix effect. Validation was carried out by a recovery assay, and
      the method was applied to samples from different sources; therefore, they had
      different compositions.

PMID- 21184539
TI  - Family coronary heart disease: a call to action.
AB  - A family history of coronary heart disease (CHD) is an accepted risk factor for
      cardiovascular events and is independent of common CHD risk factors. Advances in
      the understanding of genetic influences on CHD risk provide the opportunity to
      apply this knowledge and improve patient care. Utility of inherited
      cardiovascular risk testing exists by utilizing both phenotypes and genotypes and
      includes improved CHD risk prediction, selection of the most appropriate
      treatment, prediction of outcome, and family counseling. The major impediment to
      widespread clinical adoption of this concept involves un-reimbursed staff time,
      educational needs, access to a standardized and efficient assessment mechanism,
      and privacy issues. The link between CHD and inheritance is indisputable and the
      evidence strong and consistent. For clinicians, the question is how to utilize
      this information, in an efficient manner, in order to improve patient care and
      detection of high-risk family members.

PMID- 21184540
TI  - Low serum sodium as a poor prognostic indicator for mortality in congestive heart
      failure patients.
AB  - BACKGROUND: The incidence of congestive heart failure (CHF) has not significantly
      declined over the past 50 years, and overall survival rates are low at 5 years
      following diagnosis. Numerous studies have shown low serum sodium to be a poor
      prognostic indicator of all cause mortality in CHF patients. HYPOTHESIS: The goal
      of this hypothesis was to validate if hyponatremia is an important predictor of
      mortality in an outpatient population of CHF patients on maximal combined
      angiotensin-converting enzyme inhibitor (ACEI) and beta-blocker therapy. METHODS:
      A total of 364 (13% with hyponatremia) patients with CHF (ejection fraction [EF]
      <= 40%) were enrolled in a heart failure disease management program. The mean New
      York Heart Association (NYHA) class was II.XII. The average baseline serum sodium
      was 138.2 mEq/L. RESULTS: We evaluated the relationship between hyponatremia
      (<135 mEq/L) and all-cause mortality at 40 months. During follow-up, 8 patients
      in the hyponatremia group compared to 31 in the normonatremic group died. Results
      of Kaplan-Meier analyses indicated there were no significant differences in
      mortality between the hyponatremia and normonatremic groups (log-rank test =
      0.39). Results for Cox proportional hazards models indicated low sodium was not a
      significant predictor of mortality (unadjusted odds ratio [OR]: 1.41, 95%
      confidence interval [CI]: 0.65, 3.07; adjusted OR: 1.60, 95% CI: 0.57, 4.53).
      CONCLUSIONS: The relationship between hyponatremia and all-cause mortality did
      not reach significance. Hyponatremia did not significantly predict mortality in a
      CHF population on maximal medical therapy. Copyright (c) 2010 Wiley Periodicals,
      Inc.

PMID- 21184541
TI  - Maximum derivative of left ventricular pressure predicts cardiac mortality after
      cardiac resynchronization therapy.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) has been reported to improve
      cardiac performance. However, CRT in patients with advanced heart failure is not
      always accompanied by an improvement in survival rates. We investigated the
      association between hemodynamic studies and long-term prognosis after CRT.
      METHODS: A total of 68 consecutive patients receiving CRT devices due to advanced
      heart failure were assessed by hemodynamic study and long-term outcome after
      implantation of the device. Hemodynamic parameters were measured both with the
      CRT on and off. RESULTS: Patients demonstrated significant improvement in the
      maximum first derivative of left ventricular (LV) pressure (LV dP/dt(max) ) and
      QRS duration after periods with the CRT on. During the follow-up period of 34.9
      +/- 17.6 months, basal LV dP/dt(max) and isovolemic LV pressure half-time (T1/2),
      but not percent change in LV dP/dt(max) , were independent predictors of cardiac
      mortality or hospitalization due to heart failure after multivariate Cox
      regression analysis. The Kaplan-Meier survival analysis revealed that patients in
      the lowest basal LV dP/dt(max) tertile or the longest basal T1/2 tertile
      exhibited a significantly higher cardiac-caused mortality or heart failure
      hospitalization. CONCLUSIONS: Lower LV dP/dt(max) or longer T1/2 independently
      predicts cardiac mortality or heart failure hospitalization in patients receiving
      CRT. The assessment of the basal LV dP/dt(max) and T1/2 could provide useful
      information in long-term prognosis after CRT.

PMID- 21184542
TI  - Effects of the aging process on left ventricular systolic and diastolic
      synchronicity indexes: insights from 160 "completely" healthy volunteers.
AB  - BACKGROUND: Growing attempt to use left ventricular (LV) systolic (LVSIsys) and
      diastolic (LVSIdia) synchronicity indexes in the process of selecting potential
      responders to cardiac resynchronization therapy has created a need for normative
      reference values. HYPOTHESIS: This study sought: (1) to determine normal
      reference ranges for LVSIsys and LVSIdia, and (2) to assess their relationships
      to age and conventional parameters reflecting LV systolic and diastolic
      functions. METHODS: We recruited 160 healthy volunteers (104 men) free of any
      systemic or cardiovascular disease. Maximal difference and standard deviation of
      time to peak systolic and peak early diastolic myocardial velocities for LVSIsys
      and LVSIdia were measured using 6 and 12 segment models. RESULTS: Normal ranges
      for LVSIsys and LVSIdia obtained in this study were slightly higher than
      previously reported. The normal aging process did not significantly change
      LVSIsys, whereas LVSIdia progressively and consistently increased with age.
      Significant correlations were observed between LVSIdia and parameters
      representing LV diastolic function, that is, early mitral inflow velocity and its
      deceleration time, and early mitral annulus velocity. A physiologic increase in
      LV mass/Ht2.7 showed a weak, but significant correlation with LVSIdia (r = 0.15
      0.22), but not with LVSIsys. On multivariate analysis, an age-dependent increase
      in LVSIdia was confirmed. CONCLUSIONS: In this study, we propose age-specific
      reference ranges for LVSIsys and LVSIdia. LVSIsys remains stable throughout age
      groups, whereas LVSIdia progressively increases with age. We believe that the
      reference values provided here will be useful for defining abnormal LV
      synchronous contraction and relaxation.

PMID- 21184543
TI  - Frequency, risk factors, and effect on long-term survival of increased troponin I
      following uncomplicated elective percutaneous coronary intervention.
AB  - BACKGROUND: The frequency, risk factors for, and effect on long-term survival of
      increased troponin I (cTnI) following elective, uncomplicated percutaneous
      coronary intervention (PCI) remains uncertain. METHODS: We studied 907 patients
      undergoing elective PCI without recognized PCI complications and with at least 1
      measurement of cTnI 12 or more h following the procedure. Patients with pre-PCI
      cTnI above 0.1 ng/ml or with myocardial infarction within the previous 48 h were
      excluded. RESULTS: Maximal cTnI (TrMX) following PCI averaged 0.8 ng/ml, exceeded
      the upper normal of 0.1 ng/ml in 65.2% of patients and was 1.5 ng/ml or above in
      13.7%. Of several demographic and procedural variables examined, the only
      significant predictor of TrMX was the number of stents deployed. (p < 0.0023 95%
      confidence interval [CI]: 0.10-0.46). Significant univariate predictors of
      survival (Kaplan-Meier) were older age (p < 0.0001), diabetes (p = 0.02),
      peripheral vascular disease (p < 0.0001), obstructive lung disease (p < 0.0001),
      congestive failure (p < 0.0001), renal impairment (p < 0.0001), and TrMX of 3.62
      ng/ml or above (p = 0.0451). Independent predictors (Cox) were older age (p <
      0.0001), obstructive lung disease (p < 0.0001), congestive failure (p < 0.0001),
      and TrMX (p = 0.0272). CONCLUSIONS: Elevation of cTnI occurs in most patients
      undergoing elective, uncomplicated PCI. Deployment of multiple stents is
      associated with higher values of cTnI. Long-term survival is primarily influenced
      by age and pre-PCI comorbidities, however patients with the highest values of
      cTnI after PCI are also at increased risk of reduced survival. Significant
      independent predictors of reduced survival were older age, obstructive pulmonary
      disease, congestive failure (p < 0.0001 for each), and maximal post-PCI cTnI (p =
      0.0272).

PMID- 21184544
TI  - Myocardial performance index suggests optimal fluid loss during hemodialysis.
AB  - BACKGROUND: Patients on long-term maintenance hemodialysis (HD) are at high risk
      of developing cardiovascular disease and suffering various cardiovascular
      complications during HD. HYPOTHESIS: The purpose of this study was to evaluate
      the influence of changing loading conditions on the myocardial performance index
      (MPI) in patients on long-term HD and to specify an optimal level of fluid loss
      during HD that would maintain stable global cardiac function. METHODS: The study
      consisted of 52 patients with end-stage renal failure (ESRF), mean age 56+/-11.7
      y, range: 25-80 y, on regular HD. For each patient a complete echocardiographic
      Doppler examination was performed before and after HD. Systolic and diastolic
      parameters of left ventricular function were measured, and the myocardial
      performance index (MPI) was calculated. RESULTS: The MPI was significantly
      prolonged after HD (0.47+/-0.15 before HD versus 0.59+/-0.16 after HD, p <
      0.001). Mean change in body weight during HD was 2.1+/-0.86 kg. The MPI did not
      change significantly in patients with intradialytic weight loss up to 1.75 kg.
      CONCLUSIONS: The MPI value seems to be independent of acute preload changes only
      when fluid loss is less than 1.75 kg. A 1.75-kg fluid loss during HD seems to be
      the optimal goal. In ESRF patients on HD, the MPI seems to be a good indicator of
      global left ventricular function and potentially a valuable aid in the effort to
      maintain optimal fluid balance.

PMID- 21184545
TI  - Prognostic value of different laboratory measures of renal function for long-term
      mortality after contrast media-associated renal impairment.
AB  - BACKGROUND: Contrast media-induced nephropathy (CIN) is associated with markedly
      increased morbidity and mortality. Although creatinine is at present routinely
      used to characterize renal function, many studies and guidelines recommend using
      the estimated glomerular filtration rate (eGFR) since it was found to be much
      more accurate. HYPOTHESIS: To assess whether the eGFR or creatinine alone
      provided a better predictive value for long-term mortality after contrast media
      associated renal impairment. METHODS: From a prospective trial with 412 patients
      undergoing heart catheterization, creatinine and eGFR before and after 24 h, 48
      72 h, and 30 d after contrast-media exposure were assessed as well as long-term
      mortality. RESULTS: Univariate Cox regression models identified increases in
      creatinine after 48 h (hazard rate ratio [HRR] 1.754, 95% confidence interval
      [CI] 1.134-2.712) and 30 d (HRR 3.157, 95% CI 1.968-5.064) as well as decreases
      in eGFR after 30 d (HRR 0.962, 95% CI 0.939-0.986) to be significant predictors
      of long-term mortality. However, by multivariable Cox regression, only increases
      in creatinine after 48 h (HRR 1.608, 95% CI 1.002-2.581) and after 30 d (HRR
      2.685, 95% CI 1.598-4.511) turned out to be significant and independent
      predictors of mortality. With regard to a possibly critical threshold of
      creatinine increase, our data confirmed the historically grown increase in
      creatinine of 0.5 mg/dl or more during the first 48 h as being associated with
      increased mortality (p = 0.016, log rank test). CONCLUSIONS: Serum creatinine,
      but not eGFR, was predictive for long-term mortality, with a threshold of 0.5
      mg/dl or more indicating worse prognosis.

PMID- 21184546
TI  - Prevalence of coronary artery anomalies in 12,457 adult patients who underwent
      coronary angiography.
AB  - BACKGROUND: Coronary artery anomalies are found in 0.2% to 1.3% of patients
      undergoing coronary angiography and 0.3% of an autopsy series. We aimed to
      estimate the frequency of coronary artery anomalies in our patient population.
      METHODS: The data were collected retrospectively by analyzing the angiographic
      data of 12 457 consecutive adult patients undergoing coronary angiography between
      September 2002 and October 2007. RESULTS: Coronary artery anomalies were found in
      112 patients (0.9% incidence), 100 patients (89.3%) had origin and distribution
      anomalies, and 12 patients (10.7%) had coronary artery fistulae. Their mean age
      was 52 +/- 8 years (range, 22-79 y). Separate origins of left anterior descending
      and left circumflex coronary artery from the left sinus of Valsalva was the most
      common anomaly (63.4%). The right coronary artery rising from the left coronary
      sinus of Valsalva was found in 10 (8.9%) patients. Anomalous origin of the left
      circumflex coronary artery from the right sinus of Valsalva was seen in 10 (8.9%)
      patients. The left main coronary artery from the right coronary sinus of Valsalva
      was found in 1 (0.89%) patient while an isolated single coronary artery was seen
      in 2 (1.78%) patients. CONCLUSION: The incidence and the pattern of coronary
      artery anomalies in our patient population were almost identical with previous
      studies. Cardiologists should be aware of the coronary anomalies which may be
      associated with potentially serious cardiac events, because recognition of these
      coronary anomalies is mandatory in order to prescribe appropriate therapy.

PMID- 21184547
TI  - Predictors and long-term prognosis of angiographic slow/no-reflow phenomenon
      during emergency percutaneous coronary intervention for ST-elevated acute
      myocardial infarction.
AB  - OBJECTIVE: Angiographic slow/no-reflow during emergency percutaneous coronary
      intervention (PCI) in patients with ST-elevated acute myocardial infarction (AMI)
      may result in unfavorable outcomes. The aim of our study was to investigate the
      clinical factors and angiographic findings that predict slow/no-reflow phenomenon
      and the long-term prognosis of AMI patients with angiographic slow/no-reflow.
      METHODS: A total of 210 consecutive AMI patients, who underwent primary PCI
      within 12 hours of symptom onset were divided into a normal flow group
      (thrombolysis in myocardial infarction [TIMI] flow grade 3, n = 169) and a
      slow/no-reflow group (<=TIMI flow grade 2, n = 41), based on cineangiograms
      performed during PCI. RESULTS: A total of 41 patients (19.5%) developed slow/no
      reflow phenomenon. Univariate analysis showed that delayed reperfusion, high
      thrombus burden on baseline angiography, and acute hyperglycemia all correlated
      with slow/no-reflow (P < 0.05 for all). Multivariate analysis revealed that
      hyperglycemia on admission (>=10 mmol/L; odds ratio [OR]: 1.7, 95% confidence
      interval [CI]: 1.423-2.971, P = 0.012), reperfusion time (>=6 h; OR:1.4, 95% CI:
      1.193-1.695, P = 0.040), and high thrombus burden (OR: 1.6, 95% CI: 1.026-2.825,
      P = 0.031) were significant and independent predictors of angiographic slow/no
      reflow. The 6-month mortality and incidence of major adverse cardiac and
      cerebrovascular events (MACCE) were significantly higher in the slow/no-reflow
      group than in the normal flow group. Angiographic slow/no-reflow was
      independently predictive of MACCE (hazard ratio [HR]: 2.642, 95% CI: 1.304-5.932,
      P = 0.028). CONCLUSION: Delayed reperfusion, high thrombus burden on baseline
      angiography, and blood glucose level on admission can be used to stratify AMI
      patients into a lower or higher risk for angiographic slow/no-reflow during PCI.
      In addition, angiographic slow/no-reflow predicts an adverse outcome in AMI
      patients.

PMID- 21184548
TI  - Recurrent stent fracture in the right coronary artery.

PMID- 21184549
TI  - Do all hemolytic anemias that occur after mitral valve repair require surgical
      treatment?
AB  - We report on a 29-year-old woman with severe hemolytic anemia following mitral
      valve annuloplasty. Although hemolysis due to mechanical prosthetic mitral valve
      is well recognized, hemolytic anemia associated with mitral valve repair is an
      uncommon condition. Reoperation may be considered if the patient has serious and
      persistent anemia. Although valve replacement is suggested to be a unique
      intervention, it may not be the solution every time because of mechanical
      effects. Various mechanisms of hemolysis related to mitral valve repair were
      suggested, but sufficient and precise data is not available. In this case, we
      tried to emphasize whether all hemolytic anemias that occur after mitral valve
      repair require surgical treatment.

PMID- 21184550
TI  - Conversion of infarction-associated atrial fibrillation by restoration of atrial
      perfusion.
AB  - We report a patient who presented with new onset atrial fibrillation in the
      setting of inferior ST-segment elevation myocardial infarction (STEMI). Cardiac
      catheterization revealed proximal occlusion of the left circumflex artery.
      Balloon angioplasty and stenting restored flow to a large left atrial branch,
      with prompt conversion of the rhythm to atrial flutter, and then to sinus rhythm.
      To our knowledge this represents the first demonstration of restoration of sinus
      rhythm by reversing left atrial ischemia in the setting of STEMI.

PMID- 21184551
TI  - Cor triatriatum.

PMID- 21184552
TI  - A case of giant right atrium misinterpreted as a mediastinal mass on plain chest
      x-ray.

PMID- 21184553
TI  - Extreme hypothermia.

PMID- 21184554
TI  - Automatic external defibrillator, life vest defibrillator, or both?
AB  - The standard of practice for out-of-hospital defibrillation is the implantable
      cardioverter-defibrillator. However, much has been written and discussed about
      the use of automated external defibrillators. Not as much has been written about
      life vest wearable defibrillators.

PMID- 21184555
TI  - Endothelium as a predictor of adverse outcomes.

PMID- 21184556
TI  - Cardio-oncology/onco-cardiology.
AB  - An understanding of onco-cardiology or cardio-oncology is critical for the
      effective care of cancer patients. Virtually all antineoplastic agents are
      associated with cardiotoxicity, which can be divided into 5 categories: direct
      cytotoxic effects of chemotherapy and associated cardiac systolic dysfunction,
      cardiac ischemia, arrhythmias, pericarditis, and chemotherapy-induced
      repolarization abnormalities. Radiation therapy can also lead to coronary artery
      disease and fibrotic changes to the valves, pericardium, and myocardium. All
      patients being considered for chemotherapy, especially those who have prior
      cardiac history, should undergo detailed cardiovascular evaluation to optimize
      the treatment. Serial assessment of left ventricular systolic function and
      cardiac biomarkers might also be considered in selected patient populations.
      Cardiotoxic effects of chemotherapy might be decreased by the concurrent use of
      angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or beta
      blockers. Antiplatelet or anticoagulation therapy might be considered in patients
      with a potential hypercoagulable state associated with chemotherapy or cancer.
      Open dialogue between both cardiologists and oncologists will be required for
      optimal patient care.

PMID- 21184557
TI  - Confidential testing of cardiac examination competency in cardiology and
      noncardiology faculty and trainees: a multicenter study.
AB  - BACKGROUND: Many reported studies of medical trainees and physicians have
      demonstrated major deficiencies in correctly identifying heart sounds and
      murmurs, but cardiologists had not been tested. We previously confirmed these
      deficiencies using a 50-question multimedia cardiac examination (CE) test
      featuring video vignettes of patients with auscultatory and visible
      manifestations of cardiovascular pathology (virtual cardiac patients). Previous
      testing of 62 internal medical faculty yielded scores no better than those of
      medical students and residents. HYPOTHESIS: In this study, we tested whether
      cardiologists outperformed other physicians in cardiac examination skills, and
      whether years in practice correlated with test performance. METHODS: To obviate
      cardiologists' reluctance to be tested, the CE test was installed at 19 US
      teaching centers for confidential testing. Test scores and demographic data
      (training level, subspecialty, and years in practice) were uploaded to a secure
      database. RESULTS: The 520 tests revealed mean scores (out of 100 +/- 95%
      confidence interval) in descending order: 10 cardiology volunteer faculty (86.3
      +/- 8.0), 57 full-time cardiologists (82.0 +/- 3.3), 4 private-practice
      cardiologists (77.0 +/- 6.8), and 19 noncardiology faculty (67.3 +/- 8.8).
      Trainees' scores in descending order: 150 cardiology fellows (77.3 +/- 2.1), 78
      medical students (63.7 +/- 3.5), 95 internal medicine residents (62.7 +/- 3.2),
      and 107 family medicine residents (59.2 +/- 3.2). Faculty scores were higher in
      those trained earlier with longer practice experience. CONCLUSIONS: Academic and
      volunteer cardiologists outperformed other medical faculty, as did cardiology
      fellows. Lower scores were observed in more recently trained faculty. Remote
      testing yielded scores similar to proctored tests in comparable groups previously
      studied. No significant improvement was seen after medical school with residency
      training.

PMID- 21184558
TI  - The prevalence of endothelial dysfunction in patients with and without coronary
      artery disease.
AB  - BACKGROUND: Endothelial dysfunction (ED) is frequently present in patients
      presenting with acute or stable coronary artery disease (CAD), but it is also
      found in patients presenting with chest pain without angiographic coronary
      lesions. HYPOTHESIS: We hypothesized that even in patients without CAD, the
      presence of cardiovascular (CV) risk factors will correlate with the presence of
      ED. METHODS: Our study included a total of 341 consecutive patients referred for
      coronary angiography. We used pulse wave analysis with a finger plethysmograph
      (peripheral arterial tonometry) to determine endothelial function. Hyperemia
      ratio was calculated as the ratio of the postischemic hyperemia response relative
      to baseline measurement. RESULTS: The hyperemia ratio was significantly higher in
      patients without CAD (2.02 +/- 0.52) compared with patients with chronic CAD
      (1.81 +/- 0.44, P = 0.001) or acute CAD (1.74 +/- 0.49, P < 0.001). Prevalence of
      ED was 33%, 46%, and 58%, respectively. In multivariate analysis, the presence of
      CAD, diabetes, and cigarette smoking, and the total number of CV risk factors,
      were strong predictors of ED. In 67% of the patients without CAD but with >=3 CV
      risk factors, ED was present. CONCLUSIONS: Prevalence of ED in patients with
      chest pain depends on the presence of CAD and CV risk factors. Patients without
      CAD but with >=3 risk factors frequently presented with ED. Such patients may be
      at increased risk for future CV events and may profit from intensified therapy to
      control CV risk factors.

PMID- 21184559
TI  - Comparison of actigraphic and subjective measures of sleep in implantable
      cardioverter defibrillator and coronary artery disease patients.
AB  - BACKGROUND: Cardiac patients frequently have insomnia symptoms that may pose risk
      for future cardiac events. Poor sleep relates to hyperarousal, anxiety and
      depression, and the incidence of hypertension and myocardial infarction.
      HYPOTHESIS: The authors hypothesized that implantable cardioverter defibrillator
      (ICD) patients would have poorer sleep than coronary artery disease (CAD)
      patients related to hypervigilance for device functioning and shock discharge.
      METHODS: Authors investigated sleep efficiency and sleep latency in a sample of
      60 patients (n = 30 CAD and n = 30 ICD) without obstructive sleep apnea at the
      University of Florida & Shands Hospital. For 14 days, participants completed a
      sleep diary. Additionally, half of the total sample also used actigraphy to
      objectively measure their sleep. Measures of somatic hypervigilance and
      psychosocial distress were administered. RESULTS: Using actigraphy, mean sleep
      efficiency was poorer (69.76%) in CAD patients compared with ICD patients
      (82.80%). This difference was highly significant, F1,27 = 16.840, P < 0.001. CAD
      patients also had shorter mean total sleep times per sleep diaries compared with
      ICD patients (336.19 minutes or 5.60 hours, 430.65 minutes or 7.18 hours,
      respectively), F1,27 = 15.908, P < 0.001. CONCLUSIONS: The finding that ICD
      patients slept more efficiently than CAD patients is surprising given that CAD
      patients had higher ejection fractions and no concerns about ICD shocks. This
      difference cannot be accounted for by differences in hypervigilance, depression,
      anxiety, or physical activity. Results suggest that CAD patients may have more
      sleep problems and may warrant increased research attention.

PMID- 21184560
TI  - Obesity is an independent risk factor for heart failure: Zona Franca Cohort
      study.
AB  - BACKGROUND: Heart failure (HF) is a major problem in developed countries.
      However, its relationship with obesity remains unclear, especially in low-risk
      populations. The objective of the study was to analyze the relationship between
      obesity and HF in a low-risk Mediterranean population. HYPOTHESIS: Obesity is an
      independent predictor for HF. METHODS: A prospective community-based population
      cohort study with 10 years' follow-up was conducted at 2 healthcare centers in
      the city of Barcelona, Spain. From a registered population of 35 275, the study
      included 932 randomly selected patients without HF, age 35-84 years. Obesity was
      defined as body mass index (BMI) >=30 and HF according to European Society of
      Cardiology guidelines, confirmed by echocardiography. Cox proportional hazards
      regression was used to examine the association between obesity and heart failure.
      RESULTS: The difference in HF incidence between obese subjects (4.7%) and
      nonobese subjects (1.6%) was 3.1% (95% confidence interval [CI]: 0.7-5.5). In the
      unadjusted model, incident HF was significantly associated with BMI: the hazard
      ratio [HR] was 1.09 for every 1 kg/m2 increase (95% CI: 1.05-1.14) and 3.01 for
      BMI >=30 (95% CI: 1.34-6.77). After adjusting for age, sex, hypertension,
      ischemic heart disease, and diabetes mellitus, the results were similar: HR 1.06
      (95% CI: 1.01-1.10) and HR 2.45 for BMI >=30 (95% CI: 1.02-5.61). Overweight was
      not associated with HF in any of the models. The population-attributable risk of
      HF due to obesity was 43.0% (95% CI: 13.9-74.9). CONCLUSIONS: High rate
      differences, HRs, and attributable risk indicate that obesity is an important
      risk factor for incident HF.

PMID- 21184561
TI  - Perceived quality of care and lifestyle counseling among patients with heart
      disease.
AB  - BACKGROUND: To examine patients' perceived quality of care and reported receipt
      of information on diet and exercise related to cardiovascular disease prevention.
      METHODS: Patients admitted with acute coronary syndromes or elective cardiac
      catheterization were eligible for enrollment. Baseline medical information was
      collected through medical-record review. Patients completed surveys at the time
      of hospitalization that included items on perceived quality of care and whether
      they had received information from a healthcare provider on diet and exercise as
      related to their heart. Perceived quality of care was grouped into 3 categories:
      (1) poor to fair, (2) good, and (3) very good to excellent. RESULTS: Among the
      182 cardiac patients who completed the survey, those who reported poor to fair
      quality of care were more likely to report that they had received no advice
      regarding diet as compared with those who perceived their quality of care as good
      or very good to excellent (61%, 59%, and 26%, respectively, P < 0.0001). A
      similar pattern was observed for exercise (71%, 74%, and 36%, respectively, P <
      0.0001). CONCLUSIONS: Patients with low perceived quality of care were less
      likely to have discussed diet and exercise habits with healthcare providers.
      Improving receipt of lifestyle counseling is warranted given the central role
      that diet and exercise play in secondary prevention.

PMID- 21184562
TI  - Diastolic heart failure versus diastolic dysfunction: difference in renal
      function.
AB  - BACKGROUND: Despite the common finding of diastolic dysfunction with a preserved
      ejection fraction on routine echocardiography in elderly patients, it is unknown
      why some patients with isolated diastolic dysfunction are asymptomatic whereas
      others develop diastolic heart failure (ie, signs and symptoms of congestive
      heart failure). HYPOTHESIS: We hypothesized that renal insufficiency is more
      common in those patients with diastolic heart failure than those with diastolic
      dysfunction; it is intrinsic renal insufficiency that determines whether
      diastolic dysfunction becomes symptomatic. METHODS: We reviewed 686 consecutive
      transthoracic echocardiograms (TTEs). Patient age, race, weight, and
      cardiovascular risk factors (hypertension, diabetes, and coronary artery disease)
      were recorded. We used the Framingham Criteria for Congestive Heart Failure to
      determine the presence of diastolic heart failure by symptoms, exam findings, and
      radiological studies. Average creatinine clearance (CrCl), calculated by both
      total body weight and lean body mass, and estimated glomerular filtration rate
      (eGFR) were calculated for each group. RESULTS: Of the 686 TTEs reviewed, 18
      patients fulfilled the criteria for diastolic heart failure and 118 patients had
      asymptomatic diastolic dysfunction. There was no difference in age, race, or
      gender nor was there any difference in the echocardiographic variables of
      diastolic function or left ventricular hypertrophy between groups. Multiple
      regression analysis showed only lower CrCl (44 +/- 36 mL/min vs 76 +/- 42 mL/min,
      total body weight, P = 0.0015; and 31 +/- 24 mL/min vs 51 +/- 27 mL/min, lean
      body mass, P = 0.0012) and eGFR (44 +/- 33 mL/min/M2 vs 69 +/- 28 mL/min/M2, P =
      0.0003) were associated with diastolic heart failure. There was no significant
      difference in the presence of hypertension, diabetes, and coronary artery disease
      between groups. CONCLUSIONS: The results of this study support the hypothesis
      that patients with normal left ventricular ejection fractions but diastolic
      dysfunction develop congestive heart failure because of underlying renal
      insufficiency. A larger, prospective study is needed to confirm this hypothesis.

PMID- 21184563
TI  - Two-dimensional visualization of cholesterol and cholesteryl esters within human
      coronary plaques by near-infrared fluorescence angioscopy.
AB  - BACKGROUND: Cholesterol (C) and cholesteryl esters (CE) within coronary plaques
      are minimally visualized directly by any of the available imaging modalities in
      vivo. If they are rendered visible in vivo, the progression of coronary plaques
      and the effects of respective therapies on these plaques can be objectively
      evaluated. HYPOTHESIS: The C and CE within human coronary plaques can be
      visualized by near-infrared fluorescence angioscopy (NIRFA). METHODS: By exciting
      at 710 +/- 25 nm and emitting at 780 nm, near-infrared fluorescence (NIRF) of
      lipid components was examined by microscopy in vitro. Lipid components in 49
      plaques of 32 excised human coronary arteries were examined by NIRFA in vitro.
      Coronary plaques were examined by NIRFA in 25 patients with coronary artery
      disease. RESULTS: C, CE, and calcium (Ca) individually did not exhibit NIRF but
      did in the presence of beta-carotene, which is known to coexist with lipids in
      the vascular wall. Other substances that are contained in atherosclerotic plaques
      did not.2 The excised human coronary plaques were classified as those with NIRF
      and those without. The former plaques were classified into homogenous, doughnut
      shaped, and spotty types. Histological examinations revealed that these image
      patterns were determined by the differences in the locations of C, CE, and Ca,
      and that those deposited within 700 MUm in depth from the plaque surface were
      imaged by NIRFA. Homogenous, doughnut-shaped, or spotty NIRFA images were also
      observed in patients. CONCLUSIONS: NIRFA is feasible for 2-dimensional imaging of
      C and CE deposited in human coronary plaques.

PMID- 21184565
TI  - SETAC and a sustainable environment.

PMID- 21184566
TI  - The tissue residue approach for toxicity assessment: findings and critical
      reviews from a Society of Environmental Toxicology and Chemistry Pellston
      Workshop.
AB  - Over the past few years, the "critical body residue" approach for assessing
      toxicity based on bioaccumulated chemicals has evolved into a more expansive
      consideration of tissue residues as the dose metric when defining dose-response
      relationships, evaluating mixtures, developing protective guidelines, and
      conducting risk assessments. Hence, scientists refer to "tissue residue approach
      for toxicity assessment" or "tissue residue-effects approach" (TRA) when
      addressing ecotoxicology issues pertaining to tissue (or internal)
      concentrations. This introduction provides an overview of a SETAC Pellston
      Workshop held in 2007 to review the state of the science for using tissue
      residues as the dose metric in environmental toxicology. The key findings of the
      workshop are presented, along with recommendations for research to enhance
      understanding of toxic responses within and between species, and to advance the
      use of the TRA in assessment and management of chemicals in the environment.

PMID- 21184567
TI  - Advancing environmental toxicology through chemical dosimetry: external exposures
      versus tissue residues.
AB  - The tissue residue dose concept has been used, although in a limited manner, in
      environmental toxicology for more than 100 y. This review outlines the history of
      this approach and the technical background for organic chemicals and metals.
      Although the toxicity of both can be explained in tissue residue terms, the
      relationship between external exposure concentration, body and/or tissues dose
      surrogates, and the effective internal dose at the sites of toxic action tends to
      be more complex for metals. Various issues and current limitations related to
      research and regulatory applications are also examined. It is clear that the
      tissue residue approach (TRA) should be an integral component in future efforts
      to enhance the generation, understanding, and utility of toxicity testing data,
      both in the laboratory and in the field. To accomplish these goals, several key
      areas need to be addressed: 1) development of a risk-based interpretive framework
      linking toxicology and ecology at multiple levels of biological organization and
      incorporating organism-based dose metrics; 2) a broadly applicable, generally
      accepted classification scheme for modes/mechanisms of toxic action with explicit
      consideration of residue information to improve both single chemical and mixture
      toxicity data interpretation and regulatory risk assessment; 3) toxicity testing
      protocols updated to ensure collection of adequate residue information, along
      with toxicokinetics and toxicodynamics information, based on explicitly defined
      toxicological models accompanied by toxicological model validation; 4) continued
      development of residue-effect databases is needed ensure their ongoing utility;
      and 5) regulatory guidance incorporating residue-based testing and interpretation
      approaches, essential in various jurisdictions.

PMID- 21184568
TI  - Crucial role of mechanisms and modes of toxic action for understanding tissue
      residue toxicity and internal effect concentrations of organic chemicals.
AB  - This article reviews the mechanistic basis of the tissue residue approach for
      toxicity assessment (TRA). The tissue residue approach implies that whole-body or
      organ concentrations (residues) are a better dose metric for describing toxicity
      to aquatic organisms than is the aqueous concentration typically used in the
      external medium. Although the benefit of internal concentrations as dose metrics
      in ecotoxicology has long been recognized, the application of the tissue residue
      approach remains limited. The main factor responsible for this is the difficulty
      of measuring internal concentrations. We propose that environmental toxicology
      can advance if mechanistic considerations are implemented and toxicokinetics and
      toxicodynamics are explicitly addressed. The variability in ecotoxicological
      outcomes and species sensitivity is due in part to differences in toxicokinetics,
      which consist of several processes, including absorption, distribution,
      metabolism, and excretion (ADME), that influence internal concentrations. Using
      internal concentrations or tissue residues as the dose metric substantially
      reduces the variability in toxicity metrics among species and individuals exposed
      under varying conditions. Total internal concentrations are useful as dose
      metrics only if they represent a surrogate of the biologically effective dose,
      the concentration or dose at the target site. If there is no direct
      proportionality, we advise the implementation of comprehensive toxicokinetic
      models that include deriving the target dose. Depending on the mechanism of
      toxicity, the concentration at the target site may or may not be a sufficient
      descriptor of toxicity. The steady-state concentration of a baseline toxicant
      associated with the biological membrane is a good descriptor of the
      toxicodynamics of baseline toxicity. When assessing specific-acting and reactive
      mechanisms, additional parameters (e.g., reaction rate with the target site and
      regeneration of the target site) are needed for characterization. For
      specifically acting compounds, intrinsic potency depends on 1) affinity for, and
      2) type of interaction with, a receptor or a target enzyme. These 2 parameters
      determine the selectivity for the toxic mechanism and the sensitivity,
      respectively. Implementation of mechanistic information in toxicokinetic
      toxicodynamic (TK-TD) models may help explain time-delayed effects, toxicity
      after pulsed or fluctuating exposure, carryover toxicity after sequential pulses,
      and mixture toxicity. We believe that this mechanistic understanding of tissue
      residue toxicity will lead to improved environmental risk assessment.

PMID- 21184569
TI  - A review of the tissue residue approach for organic and organometallic compounds
      in aquatic organisms.
AB  - This paper reviews the tissue residue approach (TRA) for toxicity assessment as
      it applies to organic chemicals and some organometallic compounds (Sn, Hg, and
      Pb) in aquatic organisms. Specific emphasis was placed on evaluating key factors
      that influence interpretation of critical body residue (CBR) toxicity metrics
      including data quality issues, lipid dynamics, choice of endpoints, processes
      that alter toxicokinetics and toxicodynamics, phototoxicity, species- and life
      stage-specific sensitivities, and biotransformation. The vast majority of data
      available on TRA is derived from laboratory studies of acute lethal responses to
      organic toxicants exhibiting baseline toxicity. Application of the TRA to various
      baseline toxicants as well as substances with specific modes of action via
      receptor-mediated processes, such as chlorinated aromatic hydrocarbons,
      pesticides, and organometallics is discussed, as is application of TRA concepts
      in field assessments of tissue residues. In contrast to media-based toxicity
      relationships, CBR values tend to be less variable and less influenced by factors
      that control bioavailability and bioaccumulation, and TRA can be used to infer
      mechanisms of toxic action, evaluate the toxicity of mixtures, and interpret
      field data on bioaccumulated toxicants. If residue-effects data are not
      available, body residues can be estimated, as has been done using the target
      lipid model for baseline toxicants, to derive critical values for risk
      assessment. One of the primary unresolved issues complicating TRA for organic
      chemicals is biotransformation. Further work on the influence of
      biotransformation, a better understanding of contaminant lipid interactions, and
      an explicit understanding of the time dependency of CBRs and receptor-mediated
      toxicity are all required to advance this field. Additional residue-effects data
      on sublethal endpoints, early life stages, and a wider range of legacy and
      emergent contaminants will be needed to improve the ability to use TRA for
      organic and organometallic compounds.

PMID- 21184570
TI  - Utility of tissue residues for predicting effects of metals on aquatic organisms.
AB  - As part of a SETAC Pellston Workshop, we evaluated the potential use of metal
      tissue residues for predicting effects in aquatic organisms. This evaluation
      included consideration of different conceptual models and then development of
      several case studies on how tissue residues might be applied for metals,
      assessing the strengths and weaknesses of these different approaches. We further
      developed a new conceptual model in which metal tissue concentrations from metal
      accumulating organisms (principally invertebrates) that are relatively
      insensitive to metal toxicity could be used as predictors of effects in metal
      sensitive taxa that typically do not accumulate metals to a significant degree.
      Overall, we conclude that the use of tissue residue assessment for metals other
      than organometals has not led to the development of a generalized approach as in
      the case of organic substances. Species-specific and site-specific approaches
      have been developed for one or more metals (e.g., Ni). The use of gill tissue
      residues within the biotic ligand model is another successful application.
      Aquatic organisms contain a diverse array of homeostatic mechanisms that are both
      metal- and species-specific. As a result, use of whole-body measurements (and
      often specific organs) for metals does not lead to a defensible position
      regarding risk to the organism. Rather, we suggest that in the short term, with
      sufficient validation, species- and site-specific approaches for metals can be
      developed. In the longer term it may be possible to use metal-accumulating
      species to predict toxicity to metal-sensitive species with appropriate field
      validation.

PMID- 21184571
TI  - Tissue residue approach for chemical mixtures.
AB  - At the SETAC Pellston Workshop "The Tissue Residues Approach for Toxicity
      Assessment," held in June 2007, we discussed mixture toxicology in terms of the
      tissue residue approach (TRA). This article reviews the literature related to the
      TRA for mixtures of chemicals and recommends a practical, tiered approach that
      can be implemented in regulatory or risk assessment applications. As with the
      toxicity of individual chemicals, addressing mixture toxicity by means of the TRA
      has a number of significant advantages. Early work provided a theoretical basis
      and experimental data to support the use of TRA for mixtures; later work provided
      a field-based validation of the integration. However, subsequent development has
      been hindered by the lack of mixture toxicity data expressed in tissue or
      preferably target-site concentrations. We recommend a framework for addressing
      the toxicology of mixtures that integrates the TRA and mixture toxicology in a 3
      tier approach. Tier I uses concentration addition (CA) to estimate the toxicity
      of mixtures regardless of the mechanism of action of the components. However, the
      common approach that uses a bioaccumulation factor (BAF) to predict TR from the
      exposure-water concentration for organics must be modified slightly for metals
      because, unlike organics, the BAF for a metal changes as 1) the aqueous exposure
      concentration changes, and 2) the concentration of other metals changes. In
      addition, total tissue residues of a metal are not a good predictor of toxicity,
      because some organisms store high concentrations of metals internally in
      detoxified forms. In tier I, if the combination of measured concentrations in the
      mixture exceeds that predicted to produce adverse effects or above-reference
      levels, it is necessary to proceed to tier II. Tier II is a mixed model that
      employs CA and independent action to estimate mixture toxicity. Tiers I and II
      estimate the toxicity of mixtures to individual species. In tier III, the TRA is
      integrated with the multisubstance potentially affected fraction (ms-PAF) method
      to derive TR levels that are protective of a selected percentage of species in
      aquatic communities (e.g., hazardous concentration for 5% of the species [HC5]).

PMID- 21184572
TI  - Application of the tissue residue approach in ecological risk assessment.
AB  - The objective of this work is to present a critical review of the application of
      the tissue residue approach (TRA) in ecological risk and/or impact assessment
      (ERA) of chemical stressors and environmental criteria development. A secondary
      goal is to develop a framework for integrating the TRA into ecological
      assessments along with traditional, exposure concentration-based assessment
      approaches. Although widely recognized for its toxicological appeal, the utility
      of the TRA in specific applications will depend on numerous factors, such as
      chemical properties, exposure characteristics, assessment type, availability of
      tissue residue-response data, and ability to quantify chemical exposure.
      Therefore, the decision to use the TRA should include an evaluation of the
      relative strengths, limitations, and uncertainties among exposure and residue
      based methods for characterizing toxicological effects. Furthermore, rather than
      supplanting exposure concentration-based toxicity assessments, the TRA can be
      highly effective for evaluating and reducing uncertainty when used in a
      complementary manner (e.g., when evaluating multiple lines of evidence in field
      studies). To address limitations with the available tissue residue-response data,
      approaches for extrapolating residue-based toxicity data across species, tissues,
      and exposure durations are discussed. Some of these approaches rely on predicted
      residue-response relationships or toxicological models that have an implicit
      residue-response basis (e.g., biotic ligand model). Because risk to an organism
      is a function of both its exposure potential and inherent sensitivity (i.e., on a
      residue basis), bioaccumulation models will be required not only for translating
      tissue residue criteria into corresponding water and sediment criteria, but also
      for defining the most vulnerable species in an assemblage (i.e., highly exposed
      and highly sensitive species). Application of the TRA in ecological assessments
      and criteria development are summarized for bioaccumulative organic chemicals,
      TBT, and in situ bioassays using bivalve molluscs.

PMID- 21184573
TI  - Will genetic adaptation of natural populations to chemical pollution result in
      lower or higher tolerance to future climate change?

PMID- 21184575
TI  - Canada's environmental effects monitoring program: areas for improvement.

PMID- 21184576
TI  - Are ambient water quality criteria for copper protective of olfactory impairment
      in fish?

PMID- 21184577
TI  - Dehusking of seed by small mammals: default values for use in risk assessment.

PMID- 21184578
TI  - The canary is alive and singing: birds continue to provide invaluable information
      about our changing environment.

PMID- 21184580
TI  - Screening of human LPHN3 for variants with a potential impact on ADHD
      susceptibility.
AB  - Attention deficit hyperactivity disorder (ADHD) is the most common behavioral
      disorder in childhood, and often has effects detectable into adulthood. Advances
      in genetic linkage and association analysis have begun to elucidate some of the
      genetic factors underlying this complex disorder. Recently, we identified LPHN3,
      a novel ADHD susceptibility gene harbored in 4q, and showed that a LPHN3 common
      haplotype confers susceptibility to ADHD and predicts effectiveness of stimulant
      medication. Here we present the mutational analysis of the entire coding region
      of LPHN3 in a cohort of 139 ADHD subjects and 52 controls from across the USA. We
      identified 21 variants, of which 14 have been reported and 7 are novel. These
      include 5 missense, 8 synonymous, and 8 intronic changes. Interestingly, neither
      susceptibility nor protective haplotype alleles are associated with obviously
      significant coding region changes, or canonical splice site alterations,
      suggesting that non-coding variations determining the quantity and/or quality of
      LPHN3 isoforms are the likely contributors to this common behavioral disorder.

PMID- 21184579
TI  - From the black widow spider to human behavior: Latrophilins, a relatively unknown
      class of G protein-coupled receptors, are implicated in psychiatric disorders.
AB  - The findings of a recent study associate LPHN3, a member of the latrophilin
      family, with an increased risk of developing attention deficit/hyperactivity
      disorder (ADHD), the most common psychiatric disorder in childhood and
      adolescence. Latrophilins comprise a new family of G protein-coupled receptors of
      unknown native physiological function that mediate the neurotoxic effects of
      alpha-latrotoxin, a potent toxin found in black widow spider venom. This receptor
      toxin interaction has helped to elucidate the mechanistic aspects of
      neurotransmitter and hormone release in vertebrates. Such unprecedented discovery
      points to a new direction in the assessment of ADHD and suggest that further
      study of this receptor family may provide novel insights into the etiology and
      treatment of ADHD and other related psychiatric conditions.

PMID- 21184581
TI  - Factors associated with experiences of genetic discrimination among individuals
      at risk for Huntington disease.
AB  - The purpose of this study was to identify factors that are associated with
      experiencing genetic discrimination (GD) among individuals at risk for Huntington
      disease (HD). Multivariable logistic regression analysis was used to examine
      factors associated with experiencing GD in data from a cross-sectional, self
      report survey of 293 individuals at risk for HD. The study sample comprised 167
      genetically tested respondents, and 66 who were not tested (80% response rate).
      Overall, individuals who learn they are at risk for HD at a younger age (OR =
      3.1; 95% CI: 1.5-6.2; P = 0.002), are mutation-positive (OR = 2.8; 95% CI: 1.4
      6.0; P = 0.006), or are highly educated (OR = 2.7; 95% CI: 1.4-5.1; P = 0.002)
      are more likely to experience GD, particularly in insurance, family, and social
      settings. Further, younger age was associated with discrimination in insurance
      (OR = 0.97; 95% CI: 0.94-1.00; P = 0.038). This study provides evidence that some
      people who are at risk for HD were more likely to experience GD than others.
      Individuals who learned they are at risk for HD at a younger age and those who
      are mutation-positive were more likely to experience GD, particularly in
      insurance, family, and social settings. Younger individuals were more likely to
      experience discrimination in the insurance setting. Overall, highly educated
      individuals were also more likely to report discrimination. These results provide
      direction for clinical and family discussions, counseling practice, and policy
      aimed at mitigating experiences of GD.

PMID- 21184582
TI  - Mapping for dyslexia and related cognitive trait loci provides strong evidence
      for further risk genes on chromosome 6p21.
AB  - In a genome-wide linkage scan, we aimed at mapping risk loci for dyslexia in the
      German population. Our sample comprised 1,030 individuals from 246 dyslexia
      families which were recruited through a single-proband sib pair study design and
      a detailed assessment of dyslexia and related cognitive traits. We found evidence
      for a major dyslexia locus on chromosome 6p21. The cognitive trait rapid naming
      (objects/colors) produced a genome-wide significant LOD score of 5.87 (P = 1.00 *
      10-7) and the implicated 6p-risk region spans around 10 Mb. Although our finding
      maps close to DYX2, where the dyslexia candidate genes DCDC2 and KIAA0319 have
      already been identified, our data point to the presence of an additional risk
      gene in this region and are highlighting the impact of 6p21 in dyslexia and
      related cognitive traits.

PMID- 21184584
TI  - Increased symptoms of attention deficit hyperactivity disorder and major
      depressive disorder symptoms in Nail-patella syndrome: potential association with
      LMX1B loss-of-function.
AB  - Nail-Patella syndrome (NPS) is an autosomal dominant disorder that is the result
      of heterozygous loss-of-function mutations in LMX1B, coding for a LIM homeobox
      (LIM-HD) transcription factor. Analyses of lmx1b mutant mice have revealed the
      role of Lmx1b in the development of mesencephalic dopaminergic neurons and the
      serotonergic system; these areas have been linked with symptoms of attention
      deficit hyperactivity disorder (ADHD) and major depressive disorder (MDD). Fifty
      adults (38 females, 12 males) with NPS completed the Conners' Adult ADHD Rating
      Scales-Self-report: Long Version (CAARS) and Beck Depression Inventory-II (BDI
      II). The objective was to describe the neurobehavioral phenotype of these
      subjects and examine possible relationships between neurobehavioral symptoms and
      NPS. Elevated levels of DSM-IV-TR ADHD Inattentive symptoms were reported on the
      CAARS by 22% of the NPS sample. The BDI-II Total score was elevated for 40% of
      the NPS sample. There was a significant increase in the odds of an elevated BDI
      II Total score when any of the three CAARS scales were elevated (odds ratios
      ranging from 11.455 to 15.615). The CAARS and BDI-II did not significantly differ
      with gender, age, or education level. There was no significant association
      between genetic mutation-predicted protein status and elevations on CAARS or BDI
      II. Individuals with NPS reported co-occurring symptoms of ADHD and MDD, with
      higher levels of co-occurrence than reported in the literature for the general
      population. The co-occurrence of these symptoms may be related to mesencephalic
      dopaminergic neurologic pathway abnormalities that are a consequence of LMX1B
      loss of function.

PMID- 21184585
TI  - Association of RANBP1 haplotype with smooth pursuit eye movement abnormality.
AB  - Schizophrenia is a multifactorial disorder and smooth pursuit eye movement (SPEM)
      disturbance is proposed as one of the most consistent neurophysiological
      endophenotype in schizophrenia. The aim of this study was to examine the genetic
      association of RANBP1 polymorphisms with the risk of schizophrenia and with the
      risk of SPEM abnormality in schizophrenia patients in a Korean population. Two
      SNPs of RANBP1 were genotyped by TaqMan assay. Their genetic effect of
      single/haplotype polymorphisms on the risk of schizophrenia and SPEM abnormality
      from 354 patients and 396 controls were performed using chi2 and multiple
      regression analyses. Although no RANBP1 polymorphisms were associated with the
      risk of schizophrenia, a common haplotype, RANBP1-ht2 (rs2238798G-rs175162T),
      showed significant association with the risk of SPEM abnormality among
      schizophrenia patients after multiple correction (P(corr)  = 0.002-0.0003). The
      results of present study provide the evidence that RANBP1 on 22q11.21 locus might
      be causally related to the SPEM abnormality rather than the development of
      schizophrenia.

PMID- 21184583
TI  - Genome-wide association study of theta band event-related oscillations identifies
      serotonin receptor gene HTR7 influencing risk of alcohol dependence.
AB  - Event-related brain oscillations (EROs) represent highly heritable
      neuroelectrical correlates of human perception and cognitive performance that
      exhibit marked deficits in patients with various psychiatric disorders. We report
      the results of the first genome-wide association study (GWAS) of an ERO
      endophenotype-frontal theta ERO evoked by visual oddball targets during P300
      response in 1,064 unrelated individuals drawn from a study of alcohol dependence.
      Forty-two SNPs of the Illumina HumanHap 1 M microarray were selected from the
      theta ERO GWAS for replication in family-based samples (N = 1,095), with four
      markers revealing nominally significant association. The most significant marker
      from the two-stage study is rs4907240 located within ARID protein 5A gene
      (ARID5A) on chromosome 2q11 (unadjusted, Fisher's combined P = 3.68 * 10-6).
      However, the most intriguing association to emerge is with rs7916403 in serotonin
      receptor gene HTR7 on chromosome 10q23 (combined P = 1.53 * 10-4), implicating
      the serotonergic system in the neurophysiological underpinnings of theta EROs.
      Moreover, promising SNPs were tested for association with diagnoses of alcohol
      dependence (DSM-IV), revealing a significant relationship with the HTR7
      polymorphism among GWAS case-controls (P = 0.008). Significant recessive genetic
      effects were also detected for alcohol dependence in both case-control and family
      based samples (P = 0.031 and 0.042, respectively), with the HTR7 risk allele
      corresponding to theta ERO reductions among homozygotes. These results suggest a
      role of the serotonergic system in the biological basis of alcohol dependence and
      underscore the utility of analyzing brain oscillations as a powerful approach to
      understanding complex genetic psychiatric disorders.

PMID- 21184587
TI  - Gene-environment interactions in panic disorder and CO2 sensitivity: Effects of
      events occurring early in life.
AB  - Heterogeneous life events (LE) precede the onset of-and potentially increase the
      susceptibility to-panic disorder (PD). It remains unknown whether LE can act as
      moderators in the context of gene-by-environment interactions (G*E) that alter
      the susceptibility to PD and the related trait of CO2 sensitivity, nor it is
      known whether such moderation may depend on occurrence of events at different
      epochs in life. In 712 general population twins we analyzed by Maximum Likelihood
      analyses of ordinal data whether life (major- and stressful) events moderate the
      genetic risk for PD and CO2 sensitivity, as indexed by the 35% CO2 /65% O2
      challenge. For CO2 sensitivity, best-fitting models encompassed both additive and
      interactional effects that increased linearly with the cumulative number and
      severity (SEV) of events in lifetime. By analyzing the moderation effect of
      cumulative SEV separately for events that had occurred in adulthood (between age
      18 and 37) or during childhood-adolescence (before the 18th birthday), we found
      evidence of G*E only within the childhood-adolescence window of risk, although
      twins had rated the childhood-adolescence events as significantly (P = 0.001)
      less severe than those having occurred during adulthood. For PD, all
      interactional terms could be dropped without significant worsening of the models'
      fit. Consistently with a diathesis-stress model, LE appear to act as moderators
      of the genetic variance for CO2 sensitivity. Childhood-adolescence appears to
      constitute a sensitive period to the action of events that concur to alter the
      susceptibility to this panic-related trait.

PMID- 21184586
TI  - Exon expression and alternatively spliced genes in Tourette Syndrome.
AB  - Tourette Syndrome (TS) is diagnosed based upon clinical criteria including motor
      and vocal tics. We hypothesized that differences in exon expression and splicing
      might be useful for pathophysiology and diagnosis. To demonstrate exon expression
      and alternatively spliced gene differences in blood of individuals with TS
      compared to healthy controls (HC), RNA was isolated from the blood of 26 un
      medicated TS subjects and 23 HC. Each sample was run on Affymetrix Human Exon 1.0
      ST (HuExon) arrays and on 3' biased U133 Plus 2.0 (HuU133) arrays. To investigate
      the differentially expressed exons and transcripts, analyses of covariance
      (ANCOVA) were performed, controlling for age, gender, and batch. Differential
      alternative splicing patterns between TS and HC were identified using analyses of
      variance (ANOVA) models in Partek. Three hundred and seventy-six exon probe sets
      were differentially expressed between TS and HC (raw P < 0.005, fold change
      >|1.2|) that separated TS and HC subjects using hierarchical clustering and
      Principal Components Analysis. The probe sets predicted TS compared to HC with a
      >90% sensitivity and specificity using a 10-fold cross-validation. Ninety genes
      (transcripts) had differential expression of a single exon (raw P < 0.005) and
      were predicted to be alternatively spliced (raw P < 0.05) in TS compared to HC.
      These preliminary findings might provide insight into the pathophysiology of TS
      and potentially provide prognostic and diagnostic biomarkers. However, the
      findings are tempered by the small sample size and multiple comparisons and
      require confirmation using PCR or deep RNA sequencing and a much larger patient
      population.

PMID- 21184588
TI  - Heritability estimates for psychotic symptom dimensions in twins with psychotic
      disorders.
AB  - Factor analysis of psychotic symptoms frequently results in positive, negative,
      and disorganized dimensions, but heritability estimates have not yet been
      reported. Symptom dimensions are usually only measured in individuals with
      psychotic disorders. Here, it is valuable to assess influences acting via
      liability to psychosis and independent modifying effects. We estimated
      heritability for psychotic symptom dimensions, taking account of these issues.
      Two-hundred-and-twenty-four probandwise twin pairs (106 monozygotic, 118 same-sex
      dizygotic), where probands had psychoses, were ascertained from the Maudsley Twin
      Register in London (1948-1993). Lifetime history of DSM-III-R psychotic disorder
      and psychotic symptom dimensions was assessed from clinical records and research
      interviews and rated using the Operational Criteria Checklist. Estimates of
      heritability and environmental components of variance in liability were made with
      structural equation modeling using a causal-contingent common pathway model
      adapted for ascertainment from a clinical register. Significant heritability was
      found for DSM-III-R psychotic disorder (h2 = 90%, 95%CI 68-94%) and the
      disorganized symptom dimension (h2 = 84%, 95%CI 18-93%). The heritability for the
      disorganized dimension remained significant when influences acting through
      liability to psychosis were set to zero, suggesting that some influences on
      disorganization are modifying factors independent of psychosis liability.
      However, the relative extent of modifying factors versus influences acting
      through psychosis liability could not be clearly determined. To our knowledge,
      this study provides the first formal evidence of substantive heritability for the
      disorganized symptom dimension, and suggests that genetic loci influencing
      disorganization in individuals with psychoses are in some cases different from
      loci that influence risk of psychotic disorders themselves.

PMID- 21184589
TI  - Lack of association between G-protein coupled receptor kinase 5 gene and
      Parkinson's disease.
AB  - The major component of Lewy Bodies (LB), the pathological hallmark of Parkinson's
      disease (PD) is alpha-synuclein, most prominently phosphorylated at serine 129. G
      protein coupled receptor kinase 5 (GRK5) has been reported to phosphorylate alpha
      synuclein in vitro, enhancing the alpha-synuclein toxicity to dopaminergic
      neurons in Drosophila model. Moreover, GRK5 was found in LBs from brain of PD
      patients. A genetic association study performed in the Japanese population
      revealed haplotypic association of the GRK5 gene with susceptibility to sporadic
      PD. We aimed at investigating whether four polymorphisms within the GRK5 gene
      (rs871196, rs2420616, rs7069375, rs4752293) could represent a risk factor for
      sporadic PD in Southern Italy. We genotyped 446 patients with PD and 450 controls
      for these markers and did not find any significant association with the disease
      at allelic, genotypic and haplotypic level. Our results indicate that the GRK5
      gene does not confer risk to sporadic PD in our sample from Southern Italy.

PMID- 21184604
TI  - [Lower G.I./colon and rectum cancer].

PMID- 21184605
TI  - [Lower G.I./colon and rectum cancer. 1. Locally coordinated critical path].

PMID- 21184590
TI  - Family-based genetic association study of DLGAP3 in Tourette Syndrome.
AB  - Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder that is
      familial and highly heritable. Although genetic influences are thought to play a
      significant role in the development of TS, no definite TS susceptibility genes
      have been identified to date. TS is believed to be genetically related to both
      obsessive-compulsive disorder (OCD) and grooming disorders (GD) such as
      trichotillomania (TTM). SAP90/PSD95-associated protein 3 (SAPAP3/DLGAP3) is a
      post-synaptic scaffolding protein that is highly expressed in glutamatergic
      synapses in the striatum and has recently been investigated as a candidate gene
      in both OCD and GD studies. Given the shared familial relationship between TS,
      OCD and TTM, DLGAP3 was evaluated as a candidate TS susceptibility gene. In a
      family-based sample of 289 TS trios, 22 common single nucleotide polymorphisms
      (SNPs) in the DLGAP3 region were analyzed. Nominally significant associations
      were identified between TS and rs11264126 and two haplotypes containing
      rs11264126 and rs12141243. Secondary analyses demonstrated that these results
      cannot be explained by the presence of comorbid OCD or TTM in the sample.
      Although none of these results remained significant after correction for multiple
      hypothesis testing, DLGAP3 remains a promising candidate gene for TS.

PMID- 21184606
TI  - [Lower G. I./colon and rectum cancer. II. New therapeutic strategies applied to
      hepatic metastasis of colonic cancer].

PMID- 21184608
TI  - [Lower G. I./colon and rectum cancer. IV. Standard chemotherapy of advanced,
      recurrent colonic cancer].

PMID- 21184607
TI  - [Lower G. I./colon and rectum cancer. III. Current topics concerning
      postoperative adjuvant chemotherapy].

PMID- 21184609
TI  - Computational design and biophysical characterization of aggregation-resistant
      point mutations for gammaD crystallin illustrate a balance of conformational
      stability and intrinsic aggregation propensity.
AB  - gammaD crystallin is a natively monomeric eye-lens protein that is associated
      with hereditary juvenile cataract formation. It is an attractive model system as
      a multidomain Greek-key protein that aggregates through partially folded
      intermediates. Point mutations M69Q and S130P were used to test (1) whether the
      protein-design algorithm RosettaDesign would successfully predict mutants that
      are resistant to aggregation when combined with informatic sequence-based
      predictors of peptide aggregation propensity and (2) how the mutations affected
      relative unfolding free energies (DeltaDeltaG(un)) and intrinsic aggregation
      propensity (IAP). M69Q was predicted to have DeltaDeltaG(un) ? 0, without
      significantly affecting IAP. S130P was predicted to have DeltaDeltaG(un) ~ 0 but
      with reduced IAP. The stability, conformation, and aggregation kinetics in acidic
      solution were experimentally characterized and compared for the variants and wild
      type (WT) protein using circular dichroism and intrinsic fluorescence
      spectroscopy, calorimetric and chemical unfolding, thioflavin-T binding,
      chromatography, static laser light scattering, and kinetic modeling. Monomer
      secondary and tertiary structures of both variants were indistinguishable from
      WT, while DeltaDeltaG(un) > 0 for M69Q and DeltaDeltaG(un) < 0 for S130P.
      Surprisingly, despite being the least conformationally stable, S130P was the most
      resistant to aggregation, indicating a significant decrease of its IAP compared
      to WT and M69Q.

PMID- 21184610
TI  - Plasma protein N-glycan profiles are associated with calendar age, familial
      longevity and health.
AB  - The development of medical interventions for the preservation of disease-free
      longevity would be facilitated by markers that predict healthy aging. Altered
      protein N-glycosylation patterns have been found with increasing age and several
      disease states. Here we investigate whether glycans derived from the total
      glycoprotein pool in plasma mark familial longevity and distinguish healthy from
      unhealthy aging. Total plasma N-glycan profiles of 2396 middle aged participants
      in the Leiden Longevity Study (LLS) were obtained by glycan release, labeling,
      and subsequent HPLC analysis with fluorescence detection. After normalization and
      batch correction, several regression strategies were applied to evaluate
      associations between glycan patterns, familial longevity, and healthy aging. Two
      N-glycan features (LC-7 and LC-8) were identified to be more abundant in plasma
      of the offspring of long-lived individuals as compared to controls. These results
      were not confounded by the altered lipid status or glucose homeostasis of the
      offspring. Furthermore, a decrease in levels of LC-8 was associated with the
      occurrence of myocardial infarction (p = 0.049, coefficient = -0.065), indicating
      that plasma glycosylation patterns do not only mark familial longevity but may
      also reflect healthy aging. In conclusion, we describe two glycan features, of
      which increased levels mark familial longevity and decreased levels of one of
      these features mark the presence of cardiovascular disease.

PMID- 21184611
TI  - Secretome of human endothelial cells under shear stress.
AB  - Endothelial cells are exposed to different types of shear stress which triggers
      the secretion of subsets of proteins. In this study, we analyzed the secretome of
      endothelial cells under static, laminar, and oscillatory flow. To differentiate
      between endogenously expressed and added proteins, isolated human umbilical vein
      endothelial cells were labeled with l-Lysine-(13)C(6),(15)N(2) and l-Arginine
      (13)C(6),(15)N(4). Shear stress was applied for 24 h using a cone-and-plate
      viscometer. Proteins from the supernatants were isolated, trypsinized, and
      finally analyzed using LC-MS/MS (LTQ). Under static control condition 395
      proteins could be identified, of which 78 proteins were assigned to the secretome
      according to Swiss-Prot database. Under laminar shear stress conditions, 327
      proteins (83 secreted) and under oscillatory shear stress 507 proteins (79
      secreted) were measured. We were able to identify 6 proteins specific for control
      conditions, 8 proteins specific for laminar shear stress, and 5 proteins specific
      for oscillatory shear stress. In addition, we identified flow-specific secretion
      patterns like the increased secretion of cell adhesion proteins and of proteins
      involved in protein binding. In conclusion, the identification of shear stress
      specific secreted proteins (101 under different flow conditions) emphasizes the
      role of endothelial cells in modulating the plasma composition according to the
      physiological requirements.

PMID- 21184612
TI  - RockerBox: analysis and filtering of massive proteomics search results.
AB  - A major problem in the analysis of mass spectrometry-based proteomics data is the
      vast growth of data volume, caused by improvements in sequencing speed of mass
      spectrometers. This growth affects analysis times and storage requirements so
      severely that many analysis tools are no longer able to cope with the increased
      file sizes. We present a tool, RockerBox, to address size problems for search
      results obtained from the widely used Mascot search engine. RockerBox allows for
      a fast evaluation of large result files by means of a number of commonly accepted
      metrics that can often be viewed through charts. Moreover, result files can be
      filtered without altering their informative content, based on a number of FDR
      calculation methods. File sizes can be reduced dramatically, often to a tenth of
      their original size, thus relaxing the need for storage and computation power,
      and boosting analysis of current and future proteomics experiments.

PMID- 21184613
TI  - MIND-BEST: Web server for drugs and target discovery; design, synthesis, and
      assay of MAO-B inhibitors and theoretical-experimental study of G3PDH protein
      from Trichomonas gallinae.
AB  - Many drugs with very different affinity to a large number of receptors are
      described. Thus, in this work, we selected drug-target pairs (DTPs/nDTPs) of
      drugs with high affinity/nonaffinity for different targets. Quantitative
      structure-activity relationship (QSAR) models become a very useful tool in this
      context because they substantially reduce time and resource-consuming
      experiments. Unfortunately, most QSAR models predict activity against only one
      protein target and/or they have not been implemented on a public Web server yet,
      freely available online to the scientific community. To solve this problem, we
      developed a multitarget QSAR (mt-QSAR) classifier combining the MARCH-INSIDE
      software for the calculation of the structural parameters of drug and target with
      the linear discriminant analysis (LDA) method in order to seek the best model.
      The accuracy of the best LDA model was 94.4% (3,859/4,086 cases) for training and
      94.9% (1,909/2,012 cases) for the external validation series. In addition, we
      implemented the model into the Web portal Bio-AIMS as an online server entitled
      MARCH-INSIDE Nested Drug-Bank Exploration & Screening Tool (MIND-BEST), located
      at http://miaja.tic.udc.es/Bio-AIMS/MIND-BEST.php . This online tool is based on
      PHP/HTML/Python and MARCH-INSIDE routines. Finally, we illustrated two practical
      uses of this server with two different experiments. In experiment 1, we report
      for the first time a MIND-BEST prediction, synthesis, characterization, and MAO-A
      and MAO-B pharmacological assay of eight rasagiline derivatives, promising for
      anti-Parkinson drug design. In experiment 2, we report sampling, parasite
      culture, sample preparation, 2-DE, MALDI-TOF and -TOF/TOF MS, MASCOT search, 3D
      structure modeling with LOMETS, and MIND-BEST prediction for different peptides
      as new protein of the found in the proteome of the bird parasite Trichomonas
      gallinae, which is promising for antiparasite drug targets discovery.

PMID- 21184616
TI  - Redox behavior of rhodium 9,10-phenanthrenediimine complexes.
AB  - New square-planar rhodium complexes of the redox-active ligand 9,10
      phenenthrenediimine (phdi) have been prepared and studied. The complexes [dpp
      nacnac(CH3)]Rh(phdi) (2a; [dpp-nacnac(CH3)](-) = CH[C(Me)(N
      (i)Pr(2)C(6)H(3))](2)(-)) and [dpp-nacnac(CF3)]Rh(phdi) (2b; [dpp-nacnac(CF3)](-)
      = CH[C(CF(3))(N-(i)Pr(2)C(6)H(3))](2)(-)) have been prepared from the
      corresponding [nacnac]Rh(CO)(2) synthons by treatment with Me(3)NO in the
      presence of the phdi ligand. Complexes 2a and 2b are diamagnetic, and their
      absorption spectra are dominated by intense charge-transfer transitions
      throughout the visible region. Electrochemical studies indicate that both the
      phdi ligand and the rhodium metal center are redox-active, with the [nacnac](-)
      ligands serving to modulate the one-electron-oxidation and -reduction redox
      potentials. In the case of 2a, chemical oxidation and reduction reactions
      provided access to the one-electron-oxidized cation, [2a](+), and one-electron
      reduced anion, [2a](-), the latter of which has been characterized in the solid
      state by single-crystal X-ray diffraction. Solution electron paramagnetic
      resonance spectra of [2a](+) and [2a](-) are consistent with S = (1)/(2) spin
      systems, but surprisingly the low-temperature spectrum of [2a](-) shows a high
      degree of rhombicity, suggestive of rhodium(II) character in the reduced anion.

PMID- 21184614
TI  - Immediate consequences of cigarette smoking: rapid formation of polycyclic
      aromatic hydrocarbon diol epoxides.
AB  - Polycyclic aromatic hydrocarbons (PAH) are among the likely major causative
      agents for lung cancer in smokers. PAH require metabolic activation to exert
      their carcinogenic effects, and one important pathway proceeds through a three
      step sequence resulting in the formation of diol epoxides, which react with DNA
      to produce adducts that can cause mutations and initiate the carcinogenic
      process. However, no previous published studies have examined this critical
      pathway in humans specifically exposed to PAH by inhalation of cigarette smoke.
      This study used a unique approach employing a stable isotope derivative of
      phenanthrene, the simplest PAH with a bay region, a feature closely associated
      with PAH carcinogenicity. Twelve subjects each smoked a cigarette to which
      [D(10)]phenanthrene had been added. Plasma was analyzed for [D(10)]r-1,t-2,3,c-4
      tetrahydroxy-1,2,3,4-tetrahydrophenanthrene ([D(10)]PheT), the major end product
      of the diol epoxide metabolism pathway of phenanthrene. The analysis was
      performed by gas chromatography--negative ion chemical ionization--tandem mass
      spectrometry, using [(13)C(6)]PheT as internal standard. The results demonstrated
      that the three-step pathway resulting in the formation of diol epoxides, as
      monitored by [D(10)]PheT, occurred with remarkable rapidity. Levels of
      [D(10)]PheT in plasma of all subjects were maximal at the earliest time points
      examined, 15-30 min after smoking the cigarette containing [D(10)]phenanthrene,
      and decreased thereafter. These results demonstrate that the formation of a PAH
      diol epoxide occurs rapidly in smokers. Because PAH diol epoxides are mutagenic
      and carcinogenic, the results clearly demonstrate immediate negative health
      consequences of smoking, which should serve as a major warning to anyone
      contemplating initiating tobacco use.

PMID- 21184617
TI  - Gold-catalyzed regioselective hydration of propargyl acetates assisted by a
      neighboring carbonyl group: access to alpha-acyloxy methyl ketones and synthesis
      of (+/-)-actinopolymorphol B.
AB  - A general atom-economical approach for the synthesis of alpha-acyloxy methyl
      ketone is demonstrated through regioselective hydration of a wide range of
      propargyl acetates. Readily available catalyst comprising of 1% Ph(3)PAuCl and 1%
      AgSbF(6) in dioxane-H(2)O efficiently hydrolyzes the terminal alkynes of the
      propargyl acetate in the absence of acid promoters at ambient temperature within
      a short time. Effective regioselective hydration is facilitated by the
      neighboring carbonyl group as demonstrated through (18)O-labeling study.
      Compatibility of functional moieties and tolerance to various acid-labile
      protecting groups are observed. The catalytic condition is also suitable to
      perform hydration of TMS-substituted propargyl acetates, even though it requires
      prolonged reaction time for completion. Stereointegrity of the propargylic
      acetate is preserved during the hydration. The robustness of the system is
      successfully demonstrated through gram scale preparation of the product in nearly
      quantitative yield. The common alpha-acyloxy methyl ketone is transformed to 1,2
      diol and 1,2-amino alcohol derivatives. Synthesis of actinopolymorphol B is
      achieved for the first time involving hydration of the propargyl acetate as the
      key step.

PMID- 21184618
TI  - Standardizing the inclusion of indirect medical costs in economic evaluations.
AB  - A shortcoming of many economic evaluations is that they do not include all
      medical costs in life-years gained (also termed indirect medical costs). One of
      the reasons for this is the practical difficulties in the estimation of these
      costs. While some methods have been proposed to estimate indirect medical costs
      in a standardized manner, these methods fail to take into account that not all
      costs in life-years gained can be estimated in such a way. Costs in life-years
      gained caused by diseases related to the intervention are difficult to estimate
      in a standardized manner and should always be explicitly modelled. However, costs
      of all other (unrelated) diseases in life-years gained can be estimated in such a
      way. We propose a conceptual model of how to estimate costs of unrelated diseases
      in life-years gained in a standardized manner. Furthermore, we describe how we
      estimated the parameters of this conceptual model using various data sources and
      studies conducted in the Netherlands. Results of the estimates are embedded in a
      software package called 'Practical Application to Include future Disease costs'
      (PAID 1.0). PAID 1.0 is available as a Microsoft(r) Excel tool (available as
      Supplemental Digital Content via a link in this article) and enables researchers
      to 'switch off' those disease categories that were already included in their own
      analysis and to estimate future healthcare costs of all other diseases for
      incorporation in their economic evaluations. We assumed that total healthcare
      expenditure can be explained by age, sex and time to death, while the
      relationship between costs and these three variables differs per disease. To
      estimate values for age- and sex-specific per capita health expenditure per
      disease and healthcare provider stratified by time to death we used Dutch cost-of
      illness (COI) data for the year 2005 as a backbone. The COI data consisted of age
      and sex-specific per capita health expenditure uniquely attributed to 107
      disease categories and eight healthcare provider categories. Since the Dutch COI
      figures do not distinguish between costs of those who die at a certain age
      (decedents) and those who survive that age (survivors), we decomposed average per
      capita expenditure into parts that are attributable to decedents and survivors,
      respectively, using other data sources.

PMID- 21184619
TI  - Advances in cancer therapeutics and patient access to new drugs.
AB  - Globally, there are approximately 7.4 million cancer deaths annually,
      approximately 13% of deaths from all causes. Cancer is a disease of older people
      and, as the population ages over the next 10-20 years, we can expect an increase
      in the cancer incidence. Encouragingly, cancer mortality has stabilized in many
      countries. Part of this success may be attributed to the development of new
      cancer agents, collectively called 'targeted therapies', that are more specific
      to key components of tumour growth. Worldwide, however, one of the main factors
      that limit patient access to these important new drugs is their cost, which is
      higher than traditional chemotherapy. In this review, the clinical and
      pharmacoeconomic data of selected targeted agents are discussed. In the second
      part of this article, the challenges faced by healthcare systems in making such
      drugs available to patients is reviewed. Current strategies used by many
      countries around the world to manage cancer drug budgets are presented, along
      with a proposed approach using pharmacoeconomic methodology that may increase
      patient access.

PMID- 21184620
TI  - Efficacy, safety and pharmacokinetics of indacaterol in Caucasian and Japanese
      patients with chronic obstructive pulmonary disease: a comparison of data from
      two randomized, placebo-controlled studies.
AB  - BACKGROUND: Indacaterol is a novel, inhaled, once-daily, ultra-long-acting beta2
      adrenoceptor agonist that has been approved in the EU for the treatment of
      chronic obstructive pulmonary disease (COPD). Ethnic differences may influence
      the pharmacokinetics and pharmacodynamics of a drug, and it is therefore
      important to compare these parameters in different populations. OBJECTIVE: To
      compare the efficacy, safety and pharmacokinetics of indacaterol between
      Caucasian and Japanese patients with COPD. METHODS: Data from two randomized,
      double-blind, single-dose crossover, placebo-controlled studies in Caucasian and
      Japanese patients with moderate-to-severe COPD were compared. The two studies
      were similar in terms of study design, study population (inclusion/exclusion
      criteria), parameters examined and the indacaterol doses (150, 300 or 600 MUg)
      tested. Efficacy (primary endpoint: 24-hour post-dose [trough] forced expiratory
      volume in 1 second [FEV1]), pharmacokinetics, and safety were assessed for 24
      hours post-dose in each treatment period. RESULTS: Fifty-one Caucasian (86.3%
      male; mean age 61.8 years) patients were randomized into the first study and 50
      Japanese (92.0% male; mean age 67.2 years) patients were randomized into the
      second study; >=90% of patients completed the studies. In both studies, 24-hour
      post-dose trough FEV1 was significantly higher for all indacaterol doses versus
      placebo (p<0.001), with clinically relevant differences of 140 and 130 mL for the
      lowest (150 MUg) dose in the Caucasian and Japanese studies, respectively. In
      both studies, single doses of indacaterol provided improvements in FEV1 that were
      sustained for 24 hours (p<0.001 vs placebo at all time points). In both
      populations, the average maximum serum concentration (Cmax) of indacaterol was
      observed at the first sampling time point and pharmacokinetic profiles were
      similar between populations. The increase in exposure (Cmax and area under the
      serum concentration-time curve from time zero to 24 hours) with increasing
      indacaterol dose was similar in both populations. All indacaterol doses in both
      studies demonstrated similar safety profiles. CONCLUSION: Indacaterol provided 24
      hour bronchodilation with a fast onset of action and similar pharmacokinetic and
      safety profiles in Caucasian and Japanese patients. These findings suggest that
      ethnic factors do not influence the treatment of COPD with indacaterol.

PMID- 21184621
TI  - Effects of olmesartan medoxomil, an angiotensin II type 1 receptor antagonist, on
      plasma concentration of B-type natriuretic peptide, in hypertensive patients with
      type 2 diabetes mellitus: a preliminary, observational, open-label study.
AB  - BACKGROUND AND OBJECTIVE: Angiotensin II type 1 (AT1) receptor antagonists
      (angiotensin receptor blockers [ARBs]) are widely used for the treatment of not
      only hypertension but also cardiac dysfunction. B-type natriuretic peptide (BNP)
      is secreted mainly by the cardiac ventricle and plays an important role in the
      regulation of blood pressure (BP) and body fluid. It has been established that
      the plasma level of BNP is increased in patients with chronic heart failure in
      proportion to the severity of cardiac dysfunction. Because cardiac dysfunction is
      closely associated with a high risk of mortality in patients with diabetes
      mellitus, early identification and prevention of cardiac dysfunction are
      important. The objective of this study was to determine the effects of olmesartan
      medoxomil, a novel ARB, on the plasma level of BNP in hypertensive patients with
      type 2 diabetes. METHODS: This was a preliminary, prospective, observational,
      open-label study. Sixty-eight type 2 diabetic patients with hypertension
      (systolic BP [SBP]>=140 mmHg or diastolic BP [DBP]>=90 mmHg) received olmesartan
      medoxomil 10-20 mg/day for 24 weeks. Plasma levels of BNP, as well as several
      clinical parameters of glycaemic control and lipid metabolism, were compared
      before and after 24 weeks of treatment. Another group consisting of 22 age- and
      body mass index-matched subjects not treated with olmesartan medoxomil was
      observed for reference purposes. RESULTS: In the olmesartan medoxomil group,
      mean+/-SD SBP decreased from 152.8+/-16.4 at baseline to 146.8+/-14.4 mmHg after
      24 weeks' treatment (p<0.05); similarly, mean+/-SD DBP decreased from 85.6+/-10.5
      to 81.3+/-11.6 mmHg (p<0.05). In 53 subjects in whom plasma levels of BNP could
      be measured both before and after treatment, mean+/-SD BNP decreased from 41.3+/
      49.9 to 32.5+/-36.3 pg/mL (p<0.05). Change in plasma BNP level over the 24-week
      treatment period in the olmesartan medoxomil group was not correlated with change
      in SBP or DBP. Multiple regression analysis revealed that change in plasma BNP
      level was not correlated with baseline value of or change in any other
      parameters. No other parameters in the olmesartan medoxomil group, and no
      parameters in the non-olmesartan medoxomil reference group, showed significant
      changes. CONCLUSION: The current preliminary study showed that olmesartan
      medoxomil treatment might decrease plasma BNP levels, independent of its BP
      lowering effect, in hypertensive patients with type 2 diabetes.

PMID- 21184622
TI  - Effects of nilotinib on single-dose warfarin pharmacokinetics and
      pharmacodynamics: a randomized, single-blind, two-period crossover study in
      healthy subjects.
AB  - BACKGROUND AND OBJECTIVE: Nilotinib (Tasigna(r)), a highly selective and potent
      BCR-ABL tyrosine kinase inhibitor, is approved for the treatment of chronic
      myeloid leukaemia in the chronic phase (CML-CP) and the accelerated phase (CML
      AP) in patients resistant or intolerant to prior therapy, including imatinib.
      Nilotinib has shown competitive inhibition of cytochrome P450 enzyme (CYP) 2C9 in
      vitro, but its effect on CYP2C9 activity in humans is unknown. This study
      evaluated the effects of nilotinib on the pharmacokinetics and pharmacodynamics
      of warfarin, a sensitive CYP2C9 substrate, in healthy subjects. METHODS: Twenty
      four subjects (six female, 18 male, aged 21-65 years) were enrolled to receive a
      single oral dose of warfarin 25 mg with either a single oral dose of nilotinib
      800 mg or matching placebo (all administered 30 minutes after consumption of a
      high-fat meal) in a crossover design. Serial blood samples were collected post
      dose for determining serum concentrations of nilotinib and plasma concentrations
      of S- and R-warfarin. Prothrombin time (PT) and international normalized ratio
      (INR) values were determined as pharmacodynamic measures of warfarin activity.
      CYP2C9 genotyping was performed in all subjects using TaqMan(r) assay. RESULTS:
      Sixteen subjects were identified as CYP2C9 extensive metabolizers (EMs) and eight
      as intermediate metabolizers (IMs). There were no CYP2C9 poor metabolizers.
      Pharmacokinetic parameters of S- and R-warfarin were similar between the two
      treatments (warfarin + nilotinib vs warfarin alone) in both the EM and the IM
      groups. The geometric mean ratios (90% CIs) for the maximum concentration in
      plasma (C(max)) and area under the concentration-time curve from time zero to
      infinity (AUC(infinity)) of S-warfarin in plasma in all subjects were 0.98 (0.95,
      1.02) and 1.03 (0.99, 1.07), respectively, and for R-warfarin 1.00 (0.96, 1.04)
      and 1.02 (0.99, 1.04), respectively. Mean ratios for the maximum observed value
      and AUC from time zero to the last sampling time for PT were 1.00 (0.96, 1.04)
      and 1.00 (0.98, 1.02), respectively, and for the maximum observed value for INR
      and the AUC from time zero to the last sampling time for INR were 1.00 (0.97,
      1.03) and 1.00 (0.99, 1.01), respectively. Mean +/- SD serum nilotinib C(max) was
      1872 +/- 560  ng/mL, which is comparable to steady-state C(max) in CML and
      gastrointestinal stromal tumour patients receiving twice-daily 400  mg doses.
      Adverse events observed following either treatment were generally consistent with
      the known safety profiles of both drugs, and no new safety issues were observed.
      CONCLUSION: The study results demonstrate that nilotinib has no effect on single
      dose warfarin pharmacokinetics and pharmacodynamics. This implies that nilotinib
      is unlikely to inhibit CYP2C9 activity in human subjects. These findings suggest
      that warfarin and nilotinib may be used concurrently as needed.

PMID- 21184623
TI  - Inverse psoriasis: case presentation and review.
AB  - Inverse psoriasis is a rare form of psoriasis that affects between 3% and 7% of
      psoriasis patients. Its appearance and distribution in the flexural skin folds
      makes it a difficult disease to diagnose, and because it is thought of as a
      variant of psoriasis, there are very few studies that deal with it exclusively.
      We present a short case report of inverse psoriasis and a review of the
      literature on various facets of this disease: epidemiology, histology, clinical
      presentation, differential diagnosis, and treatment.

PMID- 21184624
TI  - What's that sound? Distance determination and aperture passage from ultrasound
      echoes.
AB  - PURPOSE: Individuals with visual impairment have difficulty detecting obstacles
      that are above waist height. A prototype device was developed to allow
      individuals to hear ultrasound reflections off environmental obstacles. The
      purpose of this research was to evaluate novices' ability to evaluate distance
      and pass through apertures using this device. METHOD: The first experiment
      evaluated the ability to judge the distance from a wall using the ultrasound
      system as compared to using auditory echolocation. The second examined time for
      passage, centreline accuracy and angle of rotation through different sized
      apertures. RESULTS: Distance judgement was found to be better with audified
      ultrasound than with auditory echolocation. When passing through apertures,
      audified ultrasound enabled centreline precision similar to that of vision, but
      individuals did not rotate their shoulders while passing through suggesting that
      more practice is necessary to combine perceptive information with proprioceptive
      action. CONCLUSIONS: The ability to judge distance and navigate through an
      environment with obstacles using a device which audifies ultrasound was shown to
      be better than using auditory echolocation, but not as effective as vision. This
      device will allow individuals with visual impairments to better detect and avoid
      environmental obstacles.

PMID- 21184625
TI  - Emerging technologies and web accessibility: research challenges and
      opportunities focussing on vision issues.
AB  - This is a technological review paper focussed on identifying both the research
      challenges and opportunities for further investigation arising from emerging
      technologies, and it does not aim to propose any recommendation or standard. It
      is focussed on blind and partially sighted World Wide Web (Web) users along with
      others who use assistive technologies. The Web is a fast moving interdisciplinary
      domain in which new technologies, techniques and research is in perpetual
      development. It is often difficult to maintain a holistic view of new
      developments within the multiple domains which together make up the Web. This
      suggests that knowledge of the current developments and predictions of future
      developments are additionally important for the accessibility community. Web
      accessibility has previously been characterised by the correction of our past
      mistakes to make the current Web fulfil the original vision of access for all.
      New technologies were not designed with accessibility in mind and technologies
      that could be useful for addressing accessibility issues were not identified or
      adopted by the accessibility community. We wish to enable the research community
      to undertake preventative measures and proactively address challenges, while
      recognising opportunities, before they become unpreventable or require
      retrospective technological enhancement. This article then reviews emerging
      trends within the Web and Web Accessibility domains.

PMID- 21184626
TI  - The development of an upper limb stroke rehabilitation robot: identification of
      clinical practices and design requirements through a survey of therapists.
AB  - PURPOSE. Timely and adequate rehabilitation after a stroke is crucial to
      maximising recovery. A way of increasing treatment access could be through
      robots, which would aid therapists in providing post-stroke rehabilitation. This
      research sought to discover the needs and preferences of therapists with respect
      to a robot that focuses on upper limb rehabilitation. Understanding requirements
      for devices could help to increase integration into clinical practice. METHODS.
      An international online survey was distributed through professional organisations
      and e-mail list services to therapists. The survey contained 85 items covering
      topics such as therapist background and treatment approach, rehabilitation aims
      and robotic rehabilitation device attributes. RESULTS. Data were analysed for 233
      respondents, most of whom were physiotherapists and occupational therapists from
      Australia, Canada and USA. Top attributes included: facilitating a variety of arm
      movements, being usable while seated, giving biofeedback to clients, having
      virtual activities specific to daily living, being useful in-home and having
      resistance adjustable to client needs. In addition, the device should cost under
      6000 USD. CONCLUSIONS. Findings from this survey provide guidance for technology
      developers regarding therapists' specifications for a robotic device for upper
      limb rehabilitation. In addition, findings offer a better understanding of how
      acceptance of such devices may be facilitated.

PMID- 21184627
TI  - Excess mortality associated with mental illness and substance use disorders among
      veteran clinic users with spinal cord injury.
AB  - PURPOSE: Among veterans with traumatic spinal cord injury (SCI) or disease
      aetiologies, examine the association between diagnosed mental illness (MI) and
      substance use disorders (SUD) on mortality after controlling for demographic and
      socioeconomic factors, SCI severity, injury duration and chronic physical
      illnesses. METHOD: Longitudinal analysis of Veteran Health Administration(VHA)
      administrative data and Medicare claims for FY 1999-2004 matched with Spinal Cord
      Dysfunction-Registry (SCD-R) of VHA clinic users (N = 8334) with SCI. SCI was
      identified through SCD-R; individual MIs (anxiety, bipolar, depressive disorders,
      psychoses, post-traumatic disorder and schizophrenia) and SUDs (tobacco, alcohol
      and/or drug) were identified through ICD-9-CM codes. Cox-proportional hazards
      regressions were used to examine association between MI and SUD and time to death
      in years. RESULTS: Among veterans with SCI, 17% died by the end of FY 2004.
      Veterans with psychosis (35%), depression (22%) and alcohol and/or drug use (20%)
      had significantly higher rates of mortality compared to those without these
      diagnoses. After adjusting for other independent variables in the study, hazards
      ratios for psychosis was 1.47 (95%CI = 1.24, 1.75), for alcohol and/or drug use
      was 1.30 (95% CI = 1.11, 1.53). CONCLUSIONS: Some types of MI and SUD were
      associated with excess mortality among veterans with SCI. Care for MI and SUD
      needs to be routinely integrated into SCI management. Future research is needed
      to determine whether depression and SUD treatment provides opportunity to improve
      survival.

PMID- 21184628
TI  - Outcomes of primary total knee arthroplasty: the impact of patient-relevant
      factors on self-reported function and quality of life.
AB  - PURPOSE: To identify factors associated with functional recovery and outcome 1
      year after total knee arthroplasty (TKA). METHODS: In the prospective follow-up
      study, all the patients (n = 75, aged 60-80 years) underwent primary TKA.
      Assessments were performed preoperatively and 12 months after surgery. The main
      measures were the Western Ontario and McMaster Universities OA Index (WOMAC) and
      the 15D. The clinical examination included analyses of comorbidity and a detailed
      knee examination. Age-standardised population values of the 15D and the Outcome
      Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT
      OARSI) criteria were used as indices of response. RESULTS: Osteoporosis, pain,
      gender, age and preoperative function of the opposite knee accounted for 29.9% of
      the variance in the change in the WOMAC function score. A preoperative score of
      the 15D below the age-standardised population level, pain, higher age and
      pulmonary disease reduced the possibility to reach the HRQOL level of the general
      population. Osteoporosis decreased the likelihood of achieving responder status
      according to the OMERACT-OARSI criteria. CONCLUSION: The baseline preoperative
      score of the 15D strongly associated with the achieved level of HRQOL after TKA.
      The findings of the present study highlight the multifactorial nature of health
      status in TKA.

PMID- 21184629
TI  - Exploring extensions to working life: job lock and predictors of decreasing work
      function in older workers.
AB  - PURPOSE:  Job lock, one form of restricted job mobility that often prevents older
      workers from retiring, is linked to existing health and work place problems. This
      study explored (i) the rate of change in work limitation for job locked and non
      job locked older workers and (ii) the factors associated with these changes over
      a 12-month period following a work injury. METHODS:  Prospective observational
      cohort study of adults aged  >=55 years. Data were collected using self-completed
      questionnaires. Individual growth modelling was used to examine the pre- and post
      injury influences on work limitation. RESULTS: Work limitation was greater in
      the job locked older workers pre-injury. Both job-locked and non-job locked
      respondents had initial post-injury decreases in work limitations, suggesting a
      positive impact of temporary post-injury accommodations. However, both groups had
      increases in work limitations over time, but the increases were greater in the
      non-job locked group. In those with job lock, return to work problems were
      associated with increases in work limitations; in those without job lock, greater
      increases were associated only with low education. CONCLUSIONS: These results
      suggest that job accommodations may be important in moderating increasing work
      limitation in job-locked older workers. Results support prior findings that job
      locked older workers have unique characteristics, perhaps requiring more tailored
      interventions to maintain them in the workforce.

PMID- 21184630
TI  - The Persian version of Trinity Amputation and Prosthetics Experience Scale:
      translation, factor structure, reliability and validity.
AB  - PURPOSE: The purpose of the present study was to translate the Trinity Amputation
      and Prosthetics Experience Scale (TAPES) into Persian and to investigate its
      psychometric properties. METHOD: A sample of 182 Persian-speaker individuals with
      lower limb amputation completed the TAPES questionnaire, of whom 103 individuals
      completed the Short Form 36 Health survey as well. The TAPES was re-administered
      to 41 participants in the retest session, with an interval of 5-7 days between
      the two sessions. Internal consistency, test-retest reproducibility,
      dimensionality, item internal consistency and discriminant validity and construct
      validity were assessed. RESULTS: Cronbach's alpha's were greater than the cut-off
      point of 0.70 for all subscales with the exception of social adjustment subscale.
      Minimum intraclass correlation coefficient of 0.70 was exceeded by all subscales
      with the exception of social activity subscale. Principle component analysis
      performed on each section of the TAPES revealed loading of all items on their
      corresponding factors. The exceptions were item 4 of social adjustment subscale
      and the single item of weight subscale. Most items were stronger measures of
      their hypothesised subscale than the other subscales. In terms of construct
      validity, 75% of a priori hypotheses were confirmed. CONCLUSIONS: The Persian
      version of TAPES seems to be a reliable and valid measure of psychological
      adaptation to artificial limb.

PMID- 21184631
TI  - Sphenoorbital meningioma: surgical technique and outcome.
AB  - OBJECT: The aim of this study was to describe the surgical technique used for
      removal of sphenoorbital meningiomas in the authors' practice and to review the
      operative outcome. METHODS: Review of the senior author's practice between 1994
      and 2009 revealed 39 patients (mean age 48 years) eligible for this study.
      Clinical presentation, surgical technique, postoperative outcome, and follow-up
      data are presented. Surgical technique is detailed, with an emphasis on
      aggressive removal consisting of drilling of the hypertrophied sphenoid bone,
      orbital wall, and anterior clinoid process, followed by tumor removal and a wide
      resection of the involved dura. A simple dural closure without reconstruction of
      the orbital roof or the lateral wall of the orbit is also described. RESULTS:
      Gross-total resection was achieved in 15 cases (38.5%), near-total resection with
      small residual in the cavernous sinus or periorbita in 20 cases (51.3%), and
      subtotal resection in 4 cases (10.3%). Postoperative complications included
      trigeminal hypesthesia in 9 patients [corrected], oculomotor palsy in 3 patients
      [corrected], and seizure in 2 patients. Seven patients had recurrence within the
      mean follow-up period of 40.7 months [corrected]. Preoperative visual deficits
      were present in 21 patients (53.8%). Of these, 14 (66.7%) experienced visual
      recovery to normal levels postoperatively.Statistical analyses revealed
      preoperative severe visual deficit and sphenoid bone hypertrophy as an
      independent risk factor and an independent favorable factor, respectively, for a
      favorable visual outcome. Proptosis was resolved (<= 2 mm) in 73.5% of the
      authors' patients. No patient had postoperative enophthalmos. CONCLUSIONS: In the
      authors' practice, surgery for sphenoorbital meningiomas consists of resection of
      the orbital/sphenoid intraosseous, intraorbital, and intradural tumor components.
      The authors believe that aggressive removal of the orbital/sphenoid intraosseous
      tumor is critical for a favorable visual outcome and tumor control. Furthermore,
      satisfactory cosmetic results can be achieved with simple reconstruction
      techniques as described.

PMID- 21184632
TI  - Petroclival meningiomas: study on outcomes, complications and recurrence rates.
AB  - OBJECT: Petroclival meningiomas are notoriously difficult lesions to manage
      surgically, given the critical neurovascular structures that are intimately
      associated with the tumors. In this paper, the authors' aim was to review their
      series of patients with petroclival meningiomas who underwent surgical treatment;
      emphasis was placed on evaluating modes of presentation, postoperative
      neurological outcome, complications, and recurrence rates. METHODS: Fifty
      patients underwent surgical treatment for petroclival meningiomas. The majority
      of the patients were women (72%). The authors retrospectively reviewed the
      patients' medical records, imaging studies, and pathology reports to analyze
      presentation, surgical approach, neurological outcomes, complications, and
      recurrence rates. RESULTS: Headache was the most common presentation (58%). The
      most commonly used approach was the transpetrous approach (in 16 patients),
      followed by the orbitozygomatic approach (in 13). Gross-total resection was
      performed in 14 patients (28%), and in the remaining patients there was residual
      tumor (72%). Eighteen patients with tumor remnants were treated with Gamma Knife
      surgery. New postoperative cranial neuropathies were noted in 22 patients (44%).
      The most common cranial nerve (CN) deficit following surgery was CN III
      dysfunction (in 11 patients) and facial weakness (in 10). In 9 patients, the CN
      dysfunction was transient (41%), and 7 patients had permanent dysfunction (32%).
      Eight patients developed hydrocephalus and all required placement of a
      ventriculoperitoneal shunt. A CSF leak was noted in only 2 patients (4%), and
      wound dehiscence was noted in 1. The CSF leaks and the wound dehiscence occurred
      in patients who were undergoing reoperations. Adequate radiographic follow-up
      (minimum 6 months) was available for 31 patients (62%). The mean follow-up was
      22.1 months. In 6 patients, tumor progression or recurrences were noted. The
      median time to recurrence was 84 months. At the time of discharge from the
      hospital, 92% of the patients had good outcomes (Glasgow Outcome Scale Scores 4
      and 5). Three patients died of causes not directly related to the surgery.
      CONCLUSIONS: Petroclival meningiomas still pose a formidable challenge to
      neurosurgeons. In their series, the authors used multiple skull base approaches
      and careful microneurosurgical technique to achieve a good functional outcome
      (Glasgow Outcome Scale Score 4 or 5) in 92% of patients, although the extent of
      gross-total resection was only 28%. The authors' primary surgical goal was to
      achieve maximal tumor resection while maintaining or improving neurological
      function. The authors favor the treatment of residual tumor or recurrent tumor
      with stereotactic radiosurgery.

PMID- 21184633
TI  - Cyclic sciatica from extrapelvic endometriosis affecting the sciatic nerve.
AB  - Sciatic (catamenial) radiculopathy, waxing and waning with the menstrual cycle,
      is an uncommon condition typically caused by pelvic endometriosis affecting the
      lumbosacral plexus or proximal sciatic nerve. The authors describe a woman with
      catamenial sciatica caused by endometriosis affecting the sciatic nerve trunk in
      the upper thigh. Symptomatic with leg pain for 5 years, this patient developed
      gluteal atrophy and sensory loss and decreased strength in the L-5
      dermatomyotome, a distribution confirmed by electromyography. Magnetic resonance
      imaging suggested thickening of the sciatic nerve at and distal to the sciatic
      notch. At operation the nerve showed extrinsic and intrinsic abnormality, proven
      to be endometriosis. Her symptoms improved, and she began gonadotropin-releasing
      hormone agonist therapy for further suppression. This very unusual case shows
      that endometriosis can affect the sciatic nerve over a range of territory inside
      and outside the pelvis, and that surgery must be appropriately directed to avoid
      negative exploration. Surgical decompression achieves good relief of symptoms,
      and medical therapy also allows sustained suppression of this disease.

PMID- 21184634
TI  - Survival of patients with malignant primary osseous spinal neoplasms: results
      from the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to
      2003.
AB  - OBJECT: Malignant primary osseous spinal neoplasms are aggressive tumors that
      remain associated with poor outcomes despite aggressive multidisciplinary
      treatment measures. To date, prognosis for patients with these tumors is based on
      results from small single-center patient series and controlled trials. Large
      population-based observational studies are lacking. To assess national trends in
      histology-specific survival, the authors reviewed patient survival data spanning
      30 years (1973-2003) from the Surveillance, Epidemiology, and End Results (SEER)
      registry, a US population-based cancer registry. METHODS: The SEER registry was
      queried to identify cases of histologically confirmed primary spinal chordoma,
      chondrosarcoma, osteosarcoma, or Ewing sarcoma using coding from the
      International Classification of Disease for Oncology, Third Edition. Association
      of survival with histology, metastasis status, tumor site, and year of diagnosis
      was assessed using Cox proportional-hazards regression analysis. RESULTS: A total
      of 1892 patients were identified with primary osseous spinal neoplasms (414 with
      chordomas, 579 with chondrosarcomas, 430 with osteosarcomas, and 469 with Ewing
      sarcomas). Chordomas presented in older patients (60 +/- 17 years; p < 0.01)
      whereas Ewing sarcoma presented in younger patients (19 +/- 11 years; p < 0.01)
      compared with patients with all other tumors. The relative incidence of each
      tumor type remained similar per decade from 1973 to 2003. African Americans
      comprised a significantly greater proportion of patients with osteosarcomas than
      other tumors (9.6% vs 3.5%, respectively; p < 0.01). Compared with the sacrum,
      the mobile spine was more likely to be the site of tumor location for chordomas
      than for all other tumors (47% vs 23%, respectively; p < 0.05). Osteosarcoma and
      Ewing sarcoma were 3 times more likely than chondrosarcoma and chordoma to
      present with metastasis (31% vs 8%, respectively). Resection was performed more
      frequently for chordoma (88%) and chondrosarcoma (89%) than for osteosarcoma
      (61%) and Ewing sarcoma (53%). Overall median survival was histology-specific
      (osteosarcoma, 11 months; Ewing sarcoma, 26 months; chondrosarcoma, 37 months;
      chordoma, 50 months) and significantly worse in patients with metastasis at
      presentation for all tumor types. Survival did not significantly differ as a
      function of site (mobile spine vs sacrum/pelvis) for any tumor type, but more
      recent year of diagnosis was associated with improved survival for isolated
      spinal Ewing sarcoma (hazard ration [HR] 0.95; p = 0.001), chondrosarcoma (HR
      0.98; p = 0.009), and chordoma (HR 0.98; p = 0.10), but not osteosarcoma.
      CONCLUSIONS: In this analysis of a 30-year, US population-based cancer registry
      (SEER), the authors provide nationally representative prognosis and survival data
      for patients with malignant primary spinal osseous neoplasms. Overall patient
      survival has improved for isolated spine tumors with advancements in care over
      the past 4 decades. These results may be helpful in providing historical controls
      for understanding the efficacy of new treatment paradigms, patient education, and
      guiding level of aggressiveness in treatment strategies.

PMID- 21184635
TI  - Stereotactic body radiotherapy for spinal metastases: current status, with a
      focus on its application in the postoperative patient.
AB  - Stereotactic body radiotherapy (SBRT) for spinal metastases is an emerging
      therapeutic option aimed at delivering high biologically effective doses to
      metastases while sparing the adjacent normal tissues. This technique has emerged
      following advances in radiation delivery that include sophisticated radiation
      treatment planning software, body immobilization devices, and capabilities of
      detecting and correcting patient positional deviations with image-guided
      radiotherapy. There are limited clinical data specifically supporting the role of
      SBRT as a superior alternative to conventional radiation in the postoperative
      patient. The focus of this review was to examine the evidence pertaining to spine
      SBRT in the treatment of spinal metastases and to provide a comprehensive
      analysis of published patterns of failure, with emphasis on the postoperative
      patient.

PMID- 21184637
TI  - Hangman's fracture: a historical and biomechanical perspective.
AB  - The execution technique of hanging, introduced by the Angle, Saxon, and Jute
      Germanic tribes during their invasions of the Roman Empire and Britain in the 5th
      century, has remained largely unchanged over time. The earliest form of a gallows
      was a tree on which prisoners were hanged. Despite the introduction of several
      modifications such as a trap door, the main mechanism of death remained
      asphyxiation. This created the opportunity for attempted revival after the
      execution, and indeed several well-known cases of survival following judicial
      hanging have been reported. It was not until the introduction of the standard
      drop by Dr. Samuel Haughton in 1866, and the so-called long drop by William
      Marwood in 1872 that hanging became a standard, humane means to achieve
      instantaneous death. Hangmen, however, fearing knot slippage, started
      substituting the subaural knot for the traditional submental knot. Subaural knots
      were not as effective, and cases of decapitation were recorded. Standardization
      of the long drop was further propagated by John Berry, an executioner who used
      mathematical calculations to estimate the correct drop length for each individual
      to be hanged. A British committee on capital sentences, led by Lord Aberdare,
      studied the execution method, and advocated for the submental knot. However, it
      was not until Frederic Wood-Jones published his seminal work in 1913 that
      cervical fractures were identified as the main mechanism of death following
      hanging in which the long drop and a submental knot were used. Schneider
      introduced the term "hangman's fracture" in 1965, and reported on the
      biomechanics and other similarities of the cervical fractures seen following
      judicial hangings and those caused by motor vehicle accidents.

PMID- 21184636
TI  - Correlation of matrix metalloproteinases-1 and -3 with patient age and grade of
      lumbar disc herniation.
AB  - OBJECT: The authors studied the histological alterations and the expression of
      matrix metalloproteinase (MMP)-1 and MMP-3 in disc specimens of patients who had
      undergone operations for lumbar disc herniation. METHODS: Forty-three lumbar disc
      specimens were evaluated histopathologically for degenerative changes and
      immunohistochemical expression of MMP-1 and MMP-3. The observed degenerative
      changes provided a degenerative score that was applied in each patient. Sections
      of disc immunostained for MMP-1 and MMP-3 were evaluated semiquantitatively.
      Patients were categorized in 3 age groups: < 30 years, between 30 and 60 years,
      and > 60 years of age. The expression of MMP-1 and MMP-3 were correlated to
      patient's age, degenerative score, and grade of lumbar disc herniation. RESULTS:
      There was no statistically significant difference in the degenerative score
      between the age groups. Degenerative changes were more pronounced in greater
      grades of herniation (p < 0.0001). In the group of patients < 30 years of age
      there was a significant correlation between MMP-1 and MMP-3 expression and both
      degenerative score and herniation grade. For the group of patients 30-60 years of
      age, there was no significant difference between MMP-1 expression and
      degenerative score, but the correlation between MMP-1 expression and grade of
      herniation was significant. There was a significant correlation between MMP-3
      expression and both degenerative score and herniation grade. Regarding the
      patients > 60 years of age, there was a significant correlation between MMP-1 and
      MMP-3 expression and both degenerative score and herniation grade. There was a
      significantly lower expression of both MMP-1 and MMP-3 in the group < 30 years of
      age compared with the other ages. No significant correlation was found in MMP-1
      and MMP-3 expression between the groups of patients who were 30-60 and > 60 years
      of age. Interestingly, in age groups > 30 years, there were no statistically
      significant differences between the expression of MMP-1 and MMP-3, whereas in
      patients < 30 years of age the expression of MMP-3 was significantly lower than
      the expression of MMP-1. CONCLUSIONS: The expression of MMP-1 and MMP-3 were
      strongly correlated to the age of the patients and the grade of herniation. An
      important finding in this study is the differential expression of MMP-1 and MMP-3
      between the age groups. In the young age group it appears that deregulation of
      MMP-1 expression is higher than that of MMP-3 in the pathogenesis of lumbar disc
      herniation.

PMID- 21184638
TI  - A computed tomography-based morphometric study of thoracic pedicle anatomy in a
      random United States trauma population.
AB  - OBJECT: The objective of this study was to establish normative data for thoracic
      pedicle anatomy in the US adult population. To this end, CT scans chosen at
      random from an adult database were evaluated to determine the ideal pedicle screw
      (PS) length, diameter, trajectory, and starting point in the thoracic spine. The
      role of patient sex and side of screw placement were also assessed. The authors
      postulated that this information would be of value in guiding safe implant size
      and placement for surgeons in training. METHODS: One hundred patients (50 males
      and 50 females) were selected via retrospective review of a hospital trauma
      registry database over a 6-month period. Patients included in the study were
      older than 18 years of age, had axial bone-window CT images of the thoracic
      spine, and had no evidence of spinal trauma. For each pedicle, the pedicle width,
      pedicle-rib width, estimated screw length, trajectory, and ideal entry point were
      measured using eFilm Lite software. Statistical analysis was performed using the
      Student t-test. RESULTS: The shortest mean estimated PS length was at T-1 (33.9
      +/- 3.3 mm), and the longest was at T-9 (44.9 +/- 4.4 mm). Pedicle screw length
      was significantly affected by patient sex; men could accommodate a PS from T1-12
      a mean of 4.0 +/- 1.0 mm longer than in women (p < 0.001). Pedicle width showed
      marked variation by spinal level, with T-4 (4.4 +/- 1.1 mm) having the narrowest
      width and T-12 (8.3 +/- 1.7 mm) having the widest. Pedicle width had an obvious
      affect on potential screw diameter; 65% of patients had a least 1 pedicle at T-4
      that was < 5 mm in diameter and therefore would not accept a 4.0-mm screw with
      1.0 mm of clearance, as compared with only 2% of patients with a similar status
      at T-12. Sex variation was also apparent, as thoracic pedicles from T-1 to T-12
      were a mean of 1.4 +/- 0.2 mm wider in men than in women (p < 0.001). The PS
      trajectory in the axial plane was measured, showing a marked decrease from T-1 to
      T-4, stabilization from T-5 to T-10, followed by a decrease at T11-12. When screw
      trajectory was stratified by side of placement, a mean of 1.7 degrees  +/- 0.5
      degrees  of increased medialization was required for ideal pedicle cannulation
      from T-3 to T-12 on the left as compared with the right side, presumably because
      of developmental changes in the vertebral body caused by the aorta (p < 0.05 for
      T3-12, except for T-5, where p = 0.051). The junction of the superior articular
      process, lamina, and the superior ridge of the transverse process was shown to be
      a conserved surface landmark for PS placement. CONCLUSIONS: Preoperative CT
      evaluation is important in choosing PS length, diameter, trajectory, and entry
      point due to variation based on spinal level, patient sex, and side of placement.
      These data are valuable for resident and fellow training to guide the safe use of
      thoracic PSs.

PMID- 21184639
TI  - Analysis of prevertebral soft-tissue swelling and dysphagia in multilevel
      anterior cervical discectomy and fusion with recombinant human bone morphogenetic
      protein-2 in patients at risk for pseudarthrosis.
AB  - OBJECT: The goal of this study was to demonstrate the incidence of fusion and
      soft-tissue swelling in multilevel anterior cervical discectomies and fusions
      (ACDFs) using polyetheretherketone (PEEK) spacers with recombinant human bone
      morphogenetic protein-2 (rhBMP-2) impregnated in a Type I collagen sponge and
      titanium plates. METHODS: A single surgeon performed 30 multilevel ACDFs using
      PEEK spacers with an rhBMP-2 impregnated collagen sponge (0.4 ml, or the
      equivalent of 0.6 mg rhBMP-2). Soft-tissue swelling was assessed using cervical
      spine radiographs on postoperative Day 1 and at 2, 6, and 10 weeks and 6 months
      after surgery. Incidence of dysphagia was assessed with the Cervical Spine
      Research Society Swallowing-Quality of Life tool. Clinical success was evaluated
      with the Neck Disability Index, neck pain scores, and arm pain scores. Final
      fusion was assessed with CT by an independent neuroradiologist. RESULTS: Patients
      were followed for 6 months unless they had an incomplete fusion; those patients
      were reassessed at 9 months. Twenty-four patients underwent 2-level ACDFs and 6
      underwent 3-level ACDFs were performed on patients with the following risk
      factors for pseudarthrosis: smoking (33%), diabetes (13%), and obesity (body mass
      index >= 30 [43%]). Seventeen percent of the patients had multiple risk factors.
      Soft-tissue swelling peaked at 2 weeks regardless of level of surgery or number
      of levels treated surgically and decreased to near preoperative levels by 6
      months. At 2 weeks, Swallowing-Quality of Life evaluation showed 19% of patients
      frequently choking on food, 4.8% frequently choking when drinking, and 47.6% with
      frequent food sticking in the throat. Scores continued to improve, and at 6
      months, 0% had frequent choking on food, 6.7% had frequent difficulty drinking,
      and 6.7% had frequent food sticking in the throat. The Neck Disability Index,
      neck pain, and arm pain scores all improved progressively over 6 months.
      Incidence of fusion was 95% at 6 months and 100% at 9 months. There were no
      rehospitalizations or reoperations for soft-tissue swelling or dysphagia.
      CONCLUSIONS: Multilevel ACDF procedures using PEEK grafts and rhBMP-2 can be
      performed safely in patients with multiple risk factors for pseudarthrosis with
      excellent fusion outcomes.

PMID- 21184640
TI  - Optimizing iliac screw fixation: a biomechanical study on screw length,
      trajectory, and diameter.
AB  - OBJECT: The authors performed a study to determine the optimal iliac screw size,
      length, and trajectory that produce the highest insertional torques. METHODS: Ten
      fresh cadavers were used and 7.5 * 140-mm and 9.5 * 140-mm iliac screws were
      placed using 3D image guidance in a randomized fashion in 1 of 2 trajectories.
      The screws were inserted from the posterior superior iliac spine (PSIS) to either
      1) supraacetabular bone or 2) the anterior inferior iliac spine (AIIS).
      Insertional torque was measured for each full revolution, and the concomitant
      depth for each torque measurement was recorded. Insertional torque was correlated
      with detailed bony anatomy. RESULTS: There was no difference in mean peak
      insertional torque between the 2 trajectories (25.6 +/- 16.4 in-lb
      [supraacetabular], 26.3 +/- 18.2 lb-in [AIIS]; p = 0.8). However, there was a
      difference between the 2 screw diameters (21.1 +/- 10.9 lb-in [7.5-mm-diameter
      screw], 33.7 +/- 19.4 lb-in [9.5-mm-diameter screw]; p = 0.0003). The greatest
      mean peak insertional torques were observed at depths greater than 80 mm (12.7 +/
      9.6 lb-in [<= 80 mm], 23.7 +/- 15.7 lb-in [> 80 mm]; p = 2.6 * 10(-7)).
      Insertional torque peaks correlated with engagement of the lateral iliac cortex
      and the superior iliac fossa. CONCLUSIONS: Although the trajectory had no effect
      on insertional torque, increased torques are achievable by placing larger
      diameter and longer screws in proximity to bony landmarks, most of which are at
      distances greater 80 mm from the entry point at the PSIS. Iliac screws longer
      than those commonly used in clinical practice can be safely and accurately placed
      using image guidance, and reproducible screw paths can be achieved.

PMID- 21184641
TI  - Biomechanics of thoracic short versus long fixation after 3-column injury.
AB  - OBJECT: Posterior screw-rod fixation for thoracic spine trauma usually involves
      fusion across long segments. Biomechanical data on screw-based short-segment
      fixation for thoracic fusion are lacking. The authors compared the effects of
      spanning short and long segments in the thoracic spine. METHODS: Seven human
      spine segments (5 segments from T-2 to T-8; 2 segments from T-3 to T-9) were
      prepared. Pure-moment loading of 6 Nm was applied to induce flexion, extension,
      lateral bending, and axial rotation while 3D motion was measured
      optoelectronically. Normal specimens were tested, and then a wedge fracture was
      created on the middle vertebra after cutting the posterior ligaments. Five
      conditions of instrumentation were tested, as follows: Step A, 4-level fixation
      plus cross-link; Step B, 2-level fixation; Step C, 2-level fixation plus cross
      link; Step D, 2-level fixation plus screws at fracture site (index); and Step E,
      2-level fixation plus index screws plus cross-link. RESULTS: Long-segment
      fixation restricted 2-level range of motion (ROM) during extension and lateral
      bending significantly better than the most rigid short-segment construct. Adding
      index screws in short-segment constructs significantly reduced ROM during
      flexion, lateral bending, and axial rotation (p < 0.03). A cross-link reduced
      axial rotation ROM (p = 0.001), not affecting other loading directions (p > 0.4).
      CONCLUSIONS: Thoracic short-segment fixation provides significantly less
      stability than long-segment fixation for the injury studied. Adding a cross-link
      to short fixation improved stability only during axial rotation. Adding a screw
      at the fracture site improved short-segment stability by an average of 25%.

PMID- 21184642
TI  - Does vertebral level of pedicle subtraction osteotomy correlate with degree of
      spinopelvic parameter correction?
AB  - OBJECT: Pedicle subtraction osteotomy (PSO) is a spinal realignment technique
      that may be used to correct sagittal spinal imbalance. Theoretically, the level
      and degree of resection via a PSO should impact the degree of sagittal plane
      correction in the setting of deformity. However, the quantitative effect of PSO
      level and focal angular change on postoperative spinopelvic parameters has not
      been well described. The purpose of this study is to analyze the relationship
      between the level/degree of PSO and changes in global sagittal balance and
      spinopelvic parameters. METHODS: In this multicenter retrospective study, 70
      patients (54 women and 16 men) underwent lumbar PSO surgery for spinal imbalance.
      Preoperative and postoperative free-standing sagittal radiographs were obtained
      and analyzed by regional curves (lumbar, thoracic, and thoracolumbar), pelvic
      parameters (pelvic incidence and pelvic tilt [PT]) and global balance (sagittal
      vertical axis [SVA] and T-1 spinopelvic inclination). Correlations between PSO
      parameters (level and degree of change in angle between the 2 adjacent vertebrae)
      and spinopelvic measurements were analyzed. RESULTS: Pedicle subtraction
      osteotomy distribution by level and degree of correction was as follows: L-1 (6
      patients, 24 degrees ), L-2 (15 patients, 24 degrees ), L-3 (29 patients, 25
      degrees ), and L-4 (20 patients, 22 degrees ). There was no significant
      difference in the focal correction achieved by PSO by level. All patients
      demonstrated changes in preoperative to postoperative parameters including
      increased lumbar lordosis (from 20 degrees  to 49 degrees , p < 0.001), increased
      thoracic kyphosis (from 30 degrees  to 38 degrees , p < 0.001), decreased SVA and
      T-1 spinopelvic inclination (from 122 to 34 mm, p < 0.001 and from +3 degrees  to
      -4 degrees , p < 0.001, respectively), and decreased PT (from 31 degrees  to 23
      degrees , p < 0.001). More caudal PSO was correlated with greater PT reduction (r
      = -0.410, p < 0.05). No correlation was found between SVA correction and PSO
      location. The PSO degree was correlated with change in thoracic kyphosis (r = 
      0.474, p < 0.001), lumbar lordosis (r = 0.667, p < 0.001), sacral slope (r =
      0.426, p < 0.001), and PT (r = -0.358, p < 0.005). CONCLUSIONS: The degree of PSO
      resection correlates more with spinopelvic parameters (lumbar lordosis, thoracic
      kyphosis, PT, and sacral slope) than PSO level. More importantly, PSO level
      impacts postoperative PT correction but not SVA.

PMID- 21184643
TI  - Total en bloc spondylectomy for spinal metastases in thyroid carcinoma.
AB  - OBJECT: Thyroid carcinoma generally has a favorable prognosis, and patients
      rarely present with distant metastases. Authors of several studies have proposed
      piecemeal resection for spinal metastases in thyroid carcinoma; however, few have
      analyzed the impact of local curative surgery such as total en bloc spondylectomy
      (TES) for thyroid carcinoma. The purposes of the present study are to determine
      the strategy of surgical treatment for spinal metastases of thyroid carcinoma and
      to evaluate the surgical results of and the prognosis associated with TES.
      METHODS: Twenty-four cases of spinal metastases were retrospectively reviewed.
      The patients included 16 women and 8 men, with a mean age of 60.7 years.
      Histological examination showed follicular carcinoma in 15 cases, papillary
      carcinoma in 8, and medullary carcinoma in 1. Total en bloc spondylectomy was
      performed in 10 cases; debulking surgery, such as piecemeal excision or eggshell
      curettage, was performed in 14. The average follow-up time was 55 months (12-180
      months). RESULTS: Four patients had no evidence of disease, 8 were alive with the
      disease, and 12 had died of the disease. The overall survival rate from the time
      of surgery was 74% at 5 years. Patients with visceral metastases had a
      significant, higher risk of death. The survival rate of patients following TES
      was 90% at 5 years, which was higher than the rate in patients who underwent
      debulking surgery (63%). However, no significant difference was observed between
      the 2 types of surgery. There was a local recurrence after debulking surgery in 8
      (57%) of 14 cases. Because of the recurrences, reoperation was required after a
      mean of 41 months. In contrast, there was a local recurrence after TES in only 1
      (10%) of 10 cases. The difference between debulking surgery and TES regarding
      local recurrence was statistically significant. CONCLUSIONS: Total en bloc
      spondylectomy with enough of a margin provided favorable local control of spinal
      metastases of thyroid carcinoma during a patient's lifetime.

PMID- 21184644
TI  - Australian national trends in stimulant dispensing: 2002-2009.
AB  - OBJECTIVE: Internationally there has been an increase in the prescriptions of
      stimulant medication. The aim of this study was to examine longitudinal national
      trends of stimulant dispensing in Australia between 2002 and 2009. METHOD:
      Government databases were retrospectively reviewed for all dispensed stimulant
      prescriptions between 2002 and 2009. Prescriptions were converted to defined
      daily dose (DDD)/1000 population/day using census data. Utilization of
      dexamphetamine and methylphenidate were analysed by source (subsidized or non
      subsidized), prescriber (general practitioner, psychiatrist or other
      specialists), gender and age of patient. RESULTS: Between 2002 and 2009,
      dispensing of stimulants in Australia increased 87% from 2.93 to 5.47 DDD/1000
      population/day. Dexamphetamine remained the most commonly dispensed stimulant,
      with rates of dispensing falling 13% from 2.02 to 1.75 DDD/1000 population/day.
      Dispensed prescriptions of methylphenidate increased 300% from 0.45 in 2002 to
      1.81 DDD/1000 population/day in 2009, attributable to the availability of long
      acting preparations. Dispensing of stimulants to males was four-fold greater than
      to females. There was substantial dispensing of dexamphetamine to those older
      than 25 years. CONCLUSIONS: Stimulant dispensing in Australia increased between
      2002 and 2009 as a result of increased dispensing of long-acting preparations of
      methylphenidate. Further research is required to determine if the increase in
      stimulant dispensing in Australia is clinically appropriate.

PMID- 21184645
TI  - A phase I study of the oral platinum agent satraplatin in sequential combination
      with capecitabine in the treatment of patients with advanced solid malignancies.
AB  - BACKGROUND: The broad spectrum of antitumor activity of both the oral platinum
      analogue satraplatin (S) and capecitabine (C), along with the advantage of their
      oral administration, prompted a clinical study aimed to define the maximum
      tolerated dose (MTD) of the combination. PATIENTS AND METHODS: Four dose levels
      of S (mg/m(2)/day) and C (mg/m(2)/day) were evaluated in adult patients with
      advanced solid tumors: 60/1650, 80/1650, 60/2000, 70/2000; a course consisted of
      28 days with sequential administration of S (days 1-5) and C (days 8-21) followed
      by one week rest. RESULTS: Thirty-seven patients were treated, 24 in the dose
      escalation and 13 in the expansion phase; at the MTD, defined at S 70/C 2000, two
      patients presented dose limiting toxicities: lack of recovery of neutropenia by
      day 42 and nausea with dose skip of C. Most frequent toxicities were nausea
      (57%), diarrhea (51%), neutropenia (46%), anorexia, fatigue, vomiting (38% each).
      Two partial responses were observed in platinum sensitive ovarian cancer and one
      in prostate cancer. CONCLUSION: At S 70/C 2000 the combination of sequential S
      and C is tolerated with manageable toxicities; its evaluation in platinum and
      fluorouracil sensitive tumor types is worthwhile because of the easier
      administration and lack of nephro- and neurotoxicity as compared to parent
      compounds.

PMID- 21184647
TI  - Xolair in asthma therapy: an overview.
AB  - Asthma is a chronic lung inflammatory disease affecting from 5 to 10% of the
      population. It generally appears with periods of crisis alternating with free
      periods, but inflammation is always present. Allergic asthma manifests with
      paroxysmal crisis of bronchospasm, hissing-like respiratory noises, dyspnea, and
      respiratory distress syndrome. Different studies have shown an increase of IgE
      serum levels in subjects suffering from allergic asthma. Xolair is a monoclonal
      antibody that binds the Cepsilon3 domain of IgEs, inducing a conformational
      change of the immunoglobulin, a concealment of FcepsilonRI and FcepsilonRII
      receptors binding sites, thus precluding binding by IgEs and therefore stopping
      the release of inflammation mediators. Xolair is indicated as add-on therapy to
      improve asthma control in adult and adolescent patients (12 years of age and
      above) suffering from severe persistent allergic asthma. The aim of this review
      is 1) to explore the safety and tolerability of Xolair in asthma therapy and 2)
      to examine recent important developments focusing on treatment strategies of
      asthma with Xolair.

PMID- 21184646
TI  - Functional drug screening assay reveals potential glioma therapeutics.
AB  - Here we describe a novel functional screening assay based on bioluminescence
      monitoring of the naturally secreted Gaussia luciferase (Gluc) in the conditioned
      medium of cultured cells. Using this assay, we identified small-molecule drugs
      that sensitized brain tumor cells to the tumor necrosis factor-related apoptosis
      inducing ligand-induced cell death. Human glioblastoma multiforme cells were
      engineered by gene transfer to express Gluc as a reporter for cell viability,
      which can be monitored over time by bioluminescence measurements using a plate
      luminometer. We have optimized the Gluc assay for screening and validated it
      using the National Institute of Neurological Disorders and Stroke (NINDS) custom
      collection II library consisting of 1,040 drugs and bioactive compounds, most of
      which are Food and Drug Administration-approved and are able to cross the blood
      brain barrier. We found that the cardiac glycosides family sensitized
      glioblastoma multiforme cells to the tumor necrosis factor-related apoptosis
      inducing ligand-induced apoptosis. In conclusion, the Gluc secretion assay is a
      robust tool for functional drug screening and can be applied to many different
      fields including cancer.

PMID- 21184648
TI  - Micronutrients at the interface between inflammation and infection--ascorbic acid
      and calciferol. Part 2: calciferol and the significance of nutrient supplements.
AB  - As explained in the first part of the article, vitamins and trace elements
      influence various metabolic functions that are directly related to immune
      function. In this context, secosteroid vitamin D has met with growing interest.
      The discussion has focused on whether and, if so, to what extent, vitamin D might
      contribute to the prevention and possibly the treatment of infections and
      autoimmune diseases. We know, for instance, that immune cells are capable of
      synthesizing calcitriol from its precursor calcidiol, whereby the former enhances
      the synthesis of antibacterial peptides by macrophages while simultaneously
      inhibiting the (auto)immune response mediated by T helper cells (Th1). Numerous
      observational studies support the hypothesis that a vitamin D deficit increases
      the risk of autoimmune diseases such as type 1 diabetes mellitus, multiple
      sclerosis, psoriasis and rheumatoid arthritis; however, there are few reliable
      interventional studies to date. In general, immune status represents a sensitive
      indicator of micronutrient supply. Conversely, the activity of the immune system
      has an effect on the status of and requirements for nutrients.

PMID- 21184649
TI  - Up-regulation of Gr1+CD11b+ population in spleen of dextran sulfate sodium
      administered mice works to repair colitis.
AB  - Dextran sulfate sodium (DSS) is commonly used in rodent IBD models to chemically
      induce acute intestinal inflammation. The acute course of colitis includes colon
      tissue damages and recovery from wounded tissues. As skin wound repair was
      delayed by splenectomy, we asked whether splenectomy would induce the delay of
      colonic wound healing. In splenectomized mice, body weight recovery, disease
      score and colon length were delayed. Surprisingly we found a great increase of
      Gr1+CD11b+ cells in spleen and bone marrow of DSS-administered mice. Anti-Gr-1
      antibody treatment worsened the DSS- administered colitis. These results indicate
      that Gr1+CD11b+ cells induced by DSS worked to repair colon wound healing and
      repair colitis.

PMID- 21184650
TI  - Micronutrients at the interface between inflammation and infection--ascorbic acid
      and calciferol: part 1, general overview with a focus on ascorbic acid.
AB  - As elements of the antioxidant system, cofactors of enzymes, components of
      transcription factors, and epigenetic modulators, micronutrients, such as
      vitamins and trace elements, influence various metabolic processes that are
      directly associated with immune functions. Specifically, the vitamins C and D
      have been shown to have significance immune function. Therefore, the objective of
      this review is to elucidate interactions between micronutrients and the immune
      system. In the initial section of this review, we present a general overview of
      interactions between the immune system and micronutrients, with a focus on the
      immunobiologically relevant functions of vitamin C. Immune competent cells
      accumulate vitamin C against a concentration gradient, with a close relationship
      between vitamin C supply and immune cell activity, especially phagocytosis
      activity and T-cell function. Accordingly, one of the consequences of vitamin C
      deficiency is impaired resistance to various pathogens, while an enhanced supply
      increases antibody activity and infection resistance.

PMID- 21184651
TI  - Polycations selectively blocking tissue factor-dependent FVII activation:
      collective in vitro anticoagulation studies.
AB  - Tissue factor (TF) is an initiator of the extrinsic blood coagulation, which is
      often susceptible to upregulation by tissue injury, advanced glycation end
      product, or diverse inflammation. TF hypercoagulability is accompanied by
      elevated generation of clotting factors (e.g., FVIIa, FXa, and thrombin) and
      fibrin production, all of which are proinflammatory. In this laboratory, our in
      vitro experimental results show that polycationic anticoagulants (compound 48/80,
      ruthenium red, polybrene, protamine, Buforin I, and cationic polyamino acids)
      intervene TF hypercoagulability at posttranslational level. Polycations
      preferentially suppress TF-dependent FVII activation with diminished FVIIa
      formation shown on Western blotting, resulting in non- or un-competitive
      inhibition on FVIIa amidolytic activity. In contrast, polycations have no effect
      on FVIIa catalysis, FXa activity, or thrombin activity per se. Polycations could
      present a new class of anticoagulants with such unique upstream downregulation of
      blood coagulation. In view of coagulation-dependent inflammation and the new
      paradigm of blood coagulation-inflammation-thrombosis circuit, the polycations as
      a new class of anticoagulants could effectively contribute to antiinflammation,
      antithrombosis, and cardioprotection. Further development of effective
      anticoagulants is of biopharmaceutical significance in broadly easing disease
      conditions.

PMID- 21184652
TI  - Cytokine therapies in Crohn's disease: where are we now and where should we go?
AB  - In the gut of patients with Crohn's disease (CD), one of the major forms of
      inflammatory bowel diseases in humans, distinct subsets of T helper (Th) cells
      produce large amounts of cytokines, which are supposed to orchestrate the immuno
      inflammatory process leading to the tissue damage. Indeed, cytokine blockers,
      including the three licensed anti-TNF-alpha and the neutralizing IL-12/p40
      antibodies, have already been tested with success in CD. More than one third of
      patients do not respond to these treatments and response can wane with time.
      Moreover, blockade of such cytokines has been reported to associate with
      development of severe side effects and/or new immune-mediated pathologies. These
      findings and our better understanding of cytokine-associated effector pathways of
      tissue destruction suggest the necessity of novel cytokine-based therapies in CD.

PMID- 21184653
TI  - Anti-inflammatory activity and clinical efficacy of a 3-month levocetirizine
      therapy in mite-allergic children.
AB  - The non-sedating third generation antihistamine levocetirizine has ample evidence
      of efficacy in allergic rhinitis. In vitro studies suggested that levocetirizine
      has anti-inflammatory properties not simply related to the antihistamine activity
      but also to regulation of eosinophils. We performed a double-blind placebo
      controlled study in 40 children allergic to house dust mites with persistent
      rhinitis with the primary aim to evaluate the anti-inflammatory efficacy of
      levocetirizine measuring eosinophil-related parameters and exhaled nitric oxide
      (eNO). After one month of treatment, a significant improvement in nasal symptom
      medication scores was observed in actively but not in placebo treated patients.
      After 3 months of treatment, a significant effect was detected on eosinophilic
      cationic protein (ECP) in nasal mucosa and on nasal eNO in active treated
      patients. This suggests that during treatment of mite-allergic children with
      levocetirizine the early improvement in nasal symptoms is due to the
      antihistamine activity, while more time is needed to achieve an effect on
      allergic inflammation.

PMID- 21184654
TI  - Correlation between circulating adhesion molecules and resistin levels in
      hypertensive type-2 diabetic patients.
AB  - BACKGROUND: Endothelial dysfunction, a common feature among hypertensive and type
      2 diabetic patients, has been associated with inflammation and increased
      concentrations of serum soluble adhesion molecules and resistin, a monocyte
      macrophage- and adipocyte-derived cytokine. THE AIM OF THIS STUDY: To determine
      if there is a correlation between the serum concentrations of ICAM-1, VCAM-1,
      Eselectin and resistin in hypertensive type-2 diabetic patients. METHODS: Thirty
      hypertensive type-2 diabetic patients were enrolled in the study. Serum ICAM-1,
      VCAM-1, E-selectin and resistin concentrations were determined by ELISA and
      correlated with the Spearman correlation coefficient. RESULTS: The patients'
      serum resistin concentrations significantly correlated with VCAM-1 (r = 0.31, p=
      0.05) concentrations but not with ICAM-1 (r = 0.29, p = >0.05) and E-selectin (r
      = 0.10, p = 0.24) concentrations. CONCLUSION: VCAM-1 and resistin may participate
      in the pathophysiology of vascular damage in hypertensive type-2 diabetic
      patients. Serum resistin concentrations may be a marker of endothelial
      dysfunction.

PMID- 21184655
TI  - Endothelin receptor antagonists as disease modifiers in systemic sclerosis.
AB  - Systemic sclerosis (SSc) is a multisystem connective tissue disease of unknown
      etiology that is characterized by inflammation, vascular dysfunction and fibrosis
      of the skin and visceral organs. SSc is clinically diverse both in terms of the
      burden of skin and organ involvement and the rate of progression of the disease.
      Recent studies indicate that the endothelin system, especially ET-1 and the ETA
      and ETB receptors may play a key role in the pathogenesis of SSc. A new class of
      drugs, endothelin receptor antagonists has been introduced for treatment of
      patients with pulmonary arterial hypertension (PAH). Bosentan, a dual endothelin
      receptor antagonist as well as Sitaxsentan and Ambrisentan, selective blockers of
      the ETA receptor have proven effective in SSc-PAH. This effect may be mediated
      through both a vasodilatory and antifibrotic effect, thus making these agents
      attractive as potential disease modifying agents for SSc.

PMID- 21184656
TI  - Models and evolution of inflammatory activities.

PMID- 21184657
TI  - Antiviral sensing in teleost fish.
AB  - Vertebrates are armed with an array of pattern recognition receptors (PRRs) to
      sense viral pathogen associated molecular patterns (PAMPs). Upon activation, the
      PRRs trigger an interferon response which is central to host antiviral defence.
      Recent studies have demonstrated that the PRR surveillance system is well
      conserved in vertebrates during evolution. In fact, most classical PRRs
      characterised in mammals, such as Toll like receptors and the RIG-I-like
      receptors, have been identified in lower vertebrates. This review summarises
      recent progress in PRR recognition of viral PAMPs in teleost fish.

PMID- 21184658
TI  - 3D modelling of three pro-inflammatory molecules in selected fish species.
AB  - The inflammatory response is the reaction of all Metazoan organisms to pathogen
      invasion that initiates when pathogen-derived molecules are recognized by
      specific pattern recognition receptors expressed mainly on cells of the innate
      immune system. The successive expression of pro-inflammatory cytokines and
      chemokines limits pathogen spread, and attracts and activates immune cells to
      help in the elimination of the invaders. In this paper we focused on the analyses
      of the 3D structures of three pro-inflammatory molecules (interleukin-1beta,
      tumor necrosis factor-alpha, interleukin-8) from selected Teleost fish species
      (Oncorhynchus mykiss, Dicentrarchus labrax, Chionodraco hamatus) generated using
      as template models those of experimental homologous proteins. These structures
      were discussed with the aim to investigate the differences between them and
      mammalian counterparts and, moreover, to verify the presence of the structural
      requirements for their biological activities, known mainly in mammals.

PMID- 21184659
TI  - Helicobacter pylori and inflammation.
AB  - Helicobacter pylori is a spiral-shaped, flagellated, microaerophilic Gram
      negative bacillus which colonizes the gastric mucosa of more than 50% of human
      population. The chronic infection generates a state of inflammation, which
      however is asymptomatic in the majority of the subjects. Nevertheless, in a
      subset of the H. pylori-infected population, the gastric inflammation may evolve
      toward chronic gastritis, peptic ulcer, gastric mucosa-associated lymphoid tissue
      (MALT) lymphoma, and gastric cancer. In brief, the stages of the H. pylori
      colonization are the following: crossing of the gastric mucus layer, adhesion to
      the gastric epithelium, and then obtaining nutrients while avoiding to be
      defeated by the host immune response. For some H. pylori colonization/virulence
      factors a specific role has been suggested in the development of the inflammation
      and in the impact on the host immune system. On the other hand, some host's
      factors have been found relevant in originating chronic gastric inflammation and
      the subsequent pathological outcome in the presence of H. pylori infection. In
      other words, both bacterial action and host response contribute to the
      pathogenesis. The host-pathogen co-adaptation resulted in a H. pylori
      colonization that in most of the cases might remain harmless; however, the
      concomitance of particular genotypes of both pathogen and host may concur to the
      development of severe pathology. Although a large body of clinical and
      experimental observations have been provided since the discovery of H. pylori, a
      further knowledge of the mechanisms of host-pathogen interaction and of those
      that lead to achieve protective immunity against this pathogen is still necessary
      to guide and make efficacious the fight against H. pylori.

PMID- 21184660
TI  - Interleukin-18, from neuroinflammation to Alzheimer's disease.
AB  - A large body of evidence on brain development and ageing has revealed that
      inflammatory processes profoundly affect brain functions during life span of
      mammalians, including humans. Activation of innate immune mechanisms leading to
      pro-inflammatory cytokine up-regulation is involved in devastating and disabling
      human brain illnesses, as Alzheimer's disease (AD), a progressive
      neurodegenerative disease that causes dementia in the elderly. Emerging data
      indicates that the cytokine Interleukin (IL)-18, one of the key mediator of
      inflammation and immune response, has relevance in the physiopathological
      processes of the brain, by ultimately influencing the integrity of neurons and
      putatively contributing to AD. In this review, the relationship between specific
      IL-18-mediated processes and AD neurodegeneration is summarized and clinical
      studies pointing to a role of the cytokine in the pathology are discussed.
      Altogether, the presented data indicate that a more complete knowledge of the
      molecular mechanisms underlying IL-18 implication in neuroinflammatory and
      neurodegenerative pathways could contribute toward the development of new
      therapeutic strategies for AD.

PMID- 21184661
TI  - Inflammation in arthropods.
AB  - The inflammatory process in arthropods includes primarily the recruitment of
      circulating hemocytes to wounds or sites of microbial infections. Melanization,
      capsule formation and clotting reactions will finally result in the sealing of
      wounds. In this review we will focus on recent research about hemolymph clotting
      and melanization reactions, and the recruitment of hemocytes to wounds and
      infections. We further describe in more detail new knowledge about crustacean
      hematopoiesis that is crucial for hemocyte recruitment to the site of an
      infection and there develop an inflammatory response. Moreover, we pay special
      attention to the gut as an important route of infection in arthropods. Since the
      gastrointestinal tract provides a first line of defense and regulation of the
      indigenous bacteria and the intestine often harbors loads of potential pathogenic
      microorganisms, the integrity of intestinal epithelium and to maintain the
      correct flora is crucial to animal health.

PMID- 21184663
TI  - Inflammatory response in molluscs: cross-taxa and evolutionary considerations.
AB  - Inflammation represents the rapid and efficient elimination of damaged tissue and
      microbes and eventually the restoration of tissue functionality. Inflammatory
      response is one of the vital reactions to body injury, acting alongside the
      restoration of homeostasis, wound repair and immune response. In mammals, wound
      healing is a process that seeks to restore tissue integrity and function, and is
      characterized by a series of biological processes including inflammatory
      response. Here, we review pioneering experiments and recent observations in
      invertebrate models suggesting that in highly divergent and evolutionary distant
      taxa, such as molluscs, insects and vertebrates, the inflammatory response could
      be driven by a pool of molecules sharing common evolutionary origin.

PMID- 21184662
TI  - Nitrosative stress during infection-induced inflammation in fish: lessons from a
      host-parasite infection model.
AB  - The inflammatory response should be considered a protective immune reaction of
      the host aimed at the removal of pathogens, sometimes irrespective of negative
      side-effects. In this review we discuss the differential contribution of
      macrophages and neutrophilic granulocytes to nitrosative stress in vivo and
      discuss how the timing and concentration of nitric oxide (NO.) are important
      factors determining the degree of nitrosative stress during parasite-induced
      inflammation. Infections of common carp (Cyprinus carpio) with the extracellular
      protozoan parasite Trypanoplasma borreli provide an excellent example of how
      adaptation and homeostasis are essential elements of the host-pathogen
      relationship. On the one hand, host-derived NO. interferes with clearance of IgM
      from the parasite surface and thus can be considered a protective immune reaction
      of the host. On the other hand, it is essential that the host limits the risks
      associated with the production of NO., preventing suppressive effects on
      lymphocyte proliferation. We review, for both host and parasite, the role of
      oxygen and nitrogen radicals in the induction of nitrosative stress and the
      importance of antioxidant compounds for protection against these radicals.
      Finally, mediators of inflammation such as cytokines, chemokines or alarmins that
      are involved in the inflammatory response will be discussed in the context of the
      carp-T. borreli infection model.

PMID- 21184664
TI  - Inflammation and innate immune response against viral infections in marine fish.
AB  - Viral infections in fish are common in both natural and cultured fish populations
      and the spread of infectious disease is a serious threat to both natural
      ecosystems and commercial exploitations. A significant body of studies have
      addressed the host response to viral infection including the efficacy of DNA
      vaccines however we still have a fragmented vision of both pathologies associated
      with viral infection and the immune response to those across fish species. Many
      studies have concentrated upon freshwater fish including the zebrafish (Danio
      rerio) and the Rainbow trout (Oncorhynchus mykiss) whereas the majority of marine
      fish studies address the Atlantic salmon (Salmo salar). Here we provide a
      comprehensive review concentrating upon the salient pathological features of the
      most common viral infections including examples of the Betanodaviruses,
      Birnaviruses, Rhabdoviruses and the Isavirus in cultured fish with emphasis where
      possible upon non-salmonid cold water adapted marine species. In parallel we
      review the current state of the art mainly in reference to gene expression
      studies describing the host innate immune response concentrating upon the
      inflammatory response and its relationship toward anti-viral immunity in fish.
      Due to the complexity of the observed responses and the limitations of candidate
      gene expression studies to describe global biological processes, recent efforts
      in the use of microarray analysis for the study of the anti-viral response have
      been highlighted including members of the Pleuronectiform and the Perciform
      families. Finally we review the potential of the zebrafish to become a
      significant biological model in the elucidation of the molecular mechanisms
      underlying the piscine immune response to viral infection.

PMID- 21184665
TI  - Blockade of MUC1 expression by glycerol guaiacolate inhibits proliferation of
      human breast cancer cells.
AB  - We sought to determine whether administration of glycerol guaiacolate at an
      optimal biological dose inhibits human breast cancer cell growth. Human breast
      cancer MCF-7 and ZR-75-1 cells were treated with glycerol guaiacolate and the
      therapeutic efficacy and biological activity of this drug was investigated on
      breast cancer cell growth. MCF-7 cells were injected into the mammary fat pad of
      overectamized female athymic nude mice. Ten days later, animals were treated with
      daily intraperitoneal injections of glycerol guaiacolate for six weeks. Tumor
      size and volume was monitored and immunohistochemistry analysis on MUC1, p21 and
      ki-67 was performed. Glycerol guaiacolate decreased breast cancer cell growth in
      a dose-dependent manner, decreased cell migration, and caused G1 cell cycle
      arrest. Our results demonstrate that glycerol guaiacolate inhibits MUC1 protein
      and mRNA expression levels and significantly increased p21 expression in human
      breast cancer cells as well as induced PARP cleavage. Similarly, glycerol
      guaiacolate inhibited breast tumor growth in vivo as well as enhanced p21
      expression and decreased breast tumor cell proliferation (ki-67 expression).
      Collectively, our results demonstrate that glycerol guaiacolate decreased MUC1
      expression and enhanced cell growth inhibition by inducing p21 expression in
      breast cancer cells. These findings suggest that glycerol guaiacolate may provide
      a novel and effective approach for the treatment of human breast cancer.

PMID- 21184666
TI  - Pomegranate extract, a prooxidant with antiproliferative and proapoptotic
      activities preferentially towards carcinoma cells.
AB  - The antiproliferative and proapoptotic effects of pomegranate extract (PE), as
      correlated with its prooxidant activity, were studied. PE exerted greater
      antiproliferative effects towards cancer, than to normal, cells, isolated from
      the human oral cavity. In cell-free systems, PE generated hydrogen peroxide
      (H(2)O(2)) in cell culture media and in phosphate buffered saline, with
      prooxidant activity increasing from acidic to alkaline pH, and oxidized
      glutathione (GSH) in an alkaline, phosphate buffer. Detection of PE-generated
      H(2)O(2) was greatly lessened in medium amended with N-acetyl-L-cysteine. Using
      HSC-2 carcinoma cells as the bioindicator, the cytotoxicity of PE was potentiated
      towards cells pretreated with the GSH depleter, 1-chloro-2,4-dinitrobenzene, and
      attenuated in cells co-treated with the H(2)O(2) scavengers, catalase, pyruvate,
      and divalent cobalt ion. Intracellular GSH was lessened in cells treated with PE;
      GSH depletion in PE-treated cells was confirmed visually with the fluorescent
      dye, Cell TrackerTM Green 5-chloromethylfluorescein diacetate. These studies
      demonstrated that the antiproliferative mechanism of PE was, in part, by
      induction of oxidative stress. The mode of cell death was by apoptosis, as shown
      by flow cytometry, activation of caspase-3, and cleavage of PARP. Lessening of
      caspase-3 activation and of PARP cleavage in cells co-treated with PE and either
      cobalt or pyruvate, respectively, as compared to PE alone, indicated that
      apoptosis was through the prooxidant nature of PE.

PMID- 21184667
TI  - Work related asthma in the textile industry.
AB  - Nowadays, occupational asthma is the most common form of occupational lung
      disease in the world. In some countries the textile industry remains an important
      source of potential agents causing occupational asthma. In the textile industry
      several agents such as cotton dust and dyes may cause occupational asthma. In
      this review, we discuss the epidemiology, pathogenesis/mechanisms, clinical
      presentations, management and prevention specific to occupational asthma in the
      textile industry.Work-related asthma risk is considerable. Current understanding
      of the mechanisms by which many textile agents cause occupational asthma is
      limited, especially for low molecular-weight sensitizers and irritants. The
      diagnosis is generally established on the basis of a suggestive history of a
      temporal association between exposure and the onset of symptoms and objective
      evidence that these symptoms are related to airflow limitation. Early diagnosis,
      elimination or reduction of exposure to the offending agent and early use of
      convenient therapy according to disease severity may play an important role in
      the prevention of long-term persistence of asthma. Its prevention in the textile
      industry should be both technical and medical. It depends on the difficulties to
      reduce dust level, the limits in arranging work station or in occupational
      rehabilitation. These difficulties are increased in small textile industry
      companies. Persistent occupational asthma in this sector is often associated with
      substantial disability and consequent impacts on income and quality of life.
      Prevention of new cases is the best approach to reduce the burden of asthma
      attributable to occupational exposures. This review also outlines different
      patents on the diagnosis and treatment of asthma.

PMID- 21184668
TI  - Therapeutic approach to multiple sclerosis by novel oral drug.
AB  - Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the
      central nervous system and the most common cause of neurological disability in
      young adults, along with a considerable clinical and pathological heterogeneity.
      Since, current therapies appear to be modest in the magnitude of their treatment
      effects, particularly in the progressive phase of this disease, thus novel
      promising therapeutic strategies might open a light horizon in approaching to an
      efficient treatment in MS. In this review, we will discuss about relevant patents
      and novel designed immunosuppressive and anti-inflammatory oral drugs promising
      for treatment of multiple sclerosis.

PMID- 21184669
TI  - Anti-inflammatory approaches that target the chemokine network.
AB  - Chemokine-ligand/receptor axes play pivotal roles in a myriad of inflammatory,
      allergic and autoimmune diseases, as well as in the promotion of tumor growth and
      metastasis. Upon insult, tissue resident cells (and cancer cells in general)
      release a defined set of inflammatory chemokines that are responsible for the
      recruitment of activated pathological leukocytes. Recruited leukocytes synthesize
      and release a host of inflammatory mediators such as chemokines, cytokines,
      reactive oxygen and nitrogen species, and proteinases. These agents are
      responsible for the maintenance and amplification of inflammatory responses, and
      are directly responsible for secondary tissue damage, promotion of autoimmunity,
      fibrosis and tissue remodelling. Many cancers are associated with the expression
      of chemokine ligands that co-opt leukocytes such as tumor associated macrophages
      which in turn provide mediators including growth factors, chemokines and
      proteinases that promote angiogenesis, tumor growth, and cancer metastasis. Here,
      we discuss the relevant patents, development and the mechanism of action of a
      range of therapeutic and potential therapeutic agents that specifically target
      the chemokine ligand and receptor network. The main approaches that will be
      highlighted here are antagonism, cell depletion and the relatively unexplored
      fields of anti-sense, gene and stem cell therapies.

PMID- 21184670
TI  - Reproducibility of different screening classifications in ultrasonography of the
      newborn hip.
AB  - BACKGROUND: Ultrasonography of the hip has gained wide acceptance as a primary
      method for diagnosis, screening and treatment monitoring of developmental hip
      dysplasia in infants. The aim of the study was to examine the degree of
      concordance of two objective classifications of hip morphology and subjective
      parameters by three investigators with different levels of experience. METHODS:
      In 207 consecutive newborns (101 boys; 106 girls) the following parameters were
      assessed: bony roof angle (alpha-angle) and cartilage roof angle (beta-angle)
      according to Graf's basic standard method, "femoral head coverage" (FHC) as
      described by Terjesen, shape of the bony roof and position of the cartilaginous
      roof. Both hips were measured twice by each investigator with a 7.5 MHz linear
      transducer (SONOLINE G60S(r) ultrasound system, SIEMENS, Erlangen, Germany).
      RESULTS: Mean kappa-coefficients for the subjective parameters shape of the bony
      roof (0.97) and position of the cartilaginous roof (1.0) demonstrated high intra
      observer reproducibility. Best results were achieved for alpha-angle, followed by
      beta-angle and finally FHC. With respect to limits of agreement, inter-observer
      reproducibility was calculated less precisely. CONCLUSIONS: Higher measurement
      differences were evaluated more in objective scorings. Those variations were
      observed by every investigator irrespective of level of experience.

PMID- 21184671
TI  - Antimicrobial resistance among producers and non-producers of extended spectrum
      beta-lactamases in urinary isolates at a tertiary Hospital in Tanzania.
AB  - BACKGROUND: Published data on the existence and magnitude of extended spectrum
      beta-lactamase (ESBL) production in urinary pathogens in local setting is
      limited. The aim of the present study was to determine the prevalence of
      antimicrobial resistance and ESBL production among Escherichia coli and
      Klebsiella spp from urine samples in a tertiary hospital. This was a cross
      sectional study conducted at Muhimbili National Hospital in Dar es Salaam,
      Tanzania. FINDINGS: A total of 270 E.coli and Klebsiella spp urinary pathogens
      from children and adults isolated from January to March 2010 were included in the
      study. E. coli and Klebsiella spp isolates were tested for antimicrobial
      susceptibility by the Clinical and Laboratory Standard Institute's disc diffusion
      method. These isolates were further screened for ESBL phenotype using cefotaxime
      and ceftazidime discs. Isolates with reduced sensitivity were confirmed using
      ESBL E-test strips. Of 270 isolates, 138 (51.1%) were E. coli and 132 (48.9%)
      were Klebsiella spp. ESBL was detected in 122 (45.2%) of all the isolates. ESBL-
      producing E. coli strains were significantly more resistance to cotrimoxazole
      (90.7%), ciprofloxacin (46.3%) and nalidixic acid (61.6%) than strains that did
      not produce ESBL (p < 0.05). Similarly, ESBL- producing Klebsiella spp strains
      were significantly more resistance to cotrimoxazole (92.6%), ciprofloxacin
      (25.0%), nalidixic acid (66.2%), and gentamicin (38.2%) than strains that did not
      produce ESBL (P < 0.05). Multi-drug resistance was found to be significantly (P <
      0.05) more in ESBL producing isolates (90.5%) than non ESBL producers (68.9%).
      The occurrence of ESBL was significantly higher among isolates from inpatients
      than outpatients [95 (50.5%) vs. 27(32.9%)] (p = 0.008). The occurrence of ESBL
      was significantly higher among isolates from children than in adults [84 (54.9%)
      vs. 38(32.5%)] (p < 0.001). CONCLUSIONS: High prevalence of ESBL-producing E.
      coli and Klebsiella spp strains was found among inpatients and children. Most of
      the ESBL- producing isolates were multi-drug resistant making available
      therapeutic choices limited. We recommend continued antibiotic surveillance as
      well comprehensive multi-center studies to address the emerging problem of ESBL
      associated infections in order to preserve the continued usefulness of most
      antimicrobial drugs. Further more conducting molecular studies will help to
      evaluate the various ESBL types.

PMID- 21184672
TI  - "Rehabilitation schools for scoliosis" thematic series: describing the methods
      and results.
AB  - The Scoliosis Rehabilitation model begins with the correct diagnosis and
      evaluation of the patient, to make treatment decisions oriented to the patient.
      The treatment is based on observation, education, scoliosis specific exercises,
      and bracing. The state of research in the field of conservative treatment is
      insufficient. There is some evidence supporting scoliosis specific exercises as a
      part of the rehabilitation treatment, however, the evidence is poor and the
      different methods are not known by most of the scientific community. The only way
      to improve the knowledge and understanding of the different physiotherapy
      methodologies (specific exercises), integrated into the whole rehabilitation
      program, is to establish a single and comprehensive source of information about
      it. This is what the SCOLIOSIS Journal is going to do through the "Rehabilitation
      Schools for Scoliosis" Thematic Series, where technical papers coming from the
      different schools will be published.

PMID- 21184673
TI  - Spinal deformities rehabilitation - state of the art review.
AB  - BACKGROUND: Medical rehabilitation aims at an improvement in function, capacity
      and participation. For the rehabilitation of spinal deformities, the goal is to
      maintain function and prevent secondary symptoms in the short- and long-term. In
      patients with scoliosis, predictable signs and symptoms include pain and reduced
      pulmonary function. MATERIALS AND METHODS: A Pub Med review was completed in
      order to reveal substantial evidence for inpatient rehabilitation as performed in
      Germany. No evidence has been found in general to support claims for actual
      inpatient rehabilitation programmes as used today. Nevertheless, as there is some
      evidence that inpatient rehabilitation may be beneficial to patients with spinal
      deformities complicated by certain additional conditions, the body of evidence
      there is for conservative treatment of spinal deformities has been reviewed in
      order to allow suggestions for outpatient conservative treatment and inpatient
      rehabilitation. DISCUSSION: Today, for both children and adolescents, we are able
      to offer intensive rehabilitation programmes lasting three to five days, which
      enable the patients to acquire the skills necessary to prevent postures fostering
      scoliosis in everyday life without missing too much of school teaching subjects
      at home. The secondary functional impairments adult scoliosis patients might
      have, as in the opinion of the author, still today require the time of 3-4 weeks
      in the clinical in-patient setting. Time to address psychosocial as well as
      somatic limitations, namely chronic pains and cardiorespiratory malfunction is
      needed to preserve the patients working capability in the long-term. CONCLUSION:
      Outpatient treatment/rehabilitation is sufficient for adolescents with spinal
      deformities.Inpatient rehabilitation is recommended for patients with spinal
      deformities and pain or severe restrictive ventilation disorder.

PMID- 21184674
TI  - Tetherin restricts direct cell-to-cell infection of HIV-1.
AB  - BACKGROUND: Tetherin (BST-2/CD317/HM1.24) is an interferon (IFN)-inducible factor
      of the innate immune system, recently shown to exert antiviral activity against
      HIV-1 and other enveloped viruses by tethering nascent viral particles to the
      cell surface, thereby inhibiting viral release. In HIV-1 infection, the viral
      protein U (Vpu) counteracts this antiviral action by down-modulating tetherin
      from the cell surface. Viral dissemination between T-cells can occur via cell
      free transmission or the more efficient direct cell-to-cell route through lipid
      raft-rich virological synapses, to which tetherin localizes. RESULTS: We
      established a flow cytometry-based co-culture assay to distinguish viral transfer
      from viral transmission and investigated the influence of tetherin on cell-to
      cell spread of HIV-1. Sup-T1 cells inducible for tetherin expression were used to
      examine the impact of effector and target cell tetherin expression on virus
      transfer and transmission. Using this assay, we showed that tetherin inhibits
      direct cell-to-cell virus transfer and transmission. Viral Vpu promoted viral
      transmission from tetherin-expressing cells by down-modulating tetherin from the
      effector cell surface. Further, we showed that tetherin on the target cell
      promotes viral transfer and transmission. Viral infectivity in itself was not
      affected by tetherin. CONCLUSION: In addition to inhibiting viral release,
      tetherin also inhibits direct cell-to-cell spread. Viral protein Vpu counteracts
      this restriction, outweighing its possible cost of fitness in cell-to-cell
      transmission. The differential role of tetherin in effector and target cells
      suggest a role for tetherin in cell-cell contacts and virological synapses.

PMID- 21184675
TI  - Lack of effect of glutamine administration to boost the innate immune system
      response in trauma patients in the intensive care unit.
AB  - INTRODUCTION: The use of glutamine as a dietary supplement is associated with a
      reduced risk of infection. We hypothesized that the underlying mechanism could be
      an increase in the expression and/or functionality of Toll-like receptors (TLR),
      key receptors sensing infections. The objective of this study was to evaluate
      whether glutamine supplementation alters the expression and functionality of TLR2
      and TLR4 in circulating monocytes of trauma patients admitted to the intensive
      care unit (ICU). METHODS: We designed a prospective, randomized and single-blind
      study. Twenty-three patients received parenteral nutrition (TPN) with a daily
      glutamine supplement of 0.35 g/kg. The control group (20 patients) received an
      isocaloric-isonitrogenated TPN. Blood samples were extracted before treatment, at
      6 and 14 days. Expression of TLR2 and TLR4 was determined by flow cytometry.
      Monocytes were stimulated with TLR specific agonists and cytokines were measured
      in cell culture supernatants. Phagocytic ability of monocytes was also
      determined. RESULTS: Basal characteristics were similar in both groups. Monocytes
      from patients treated with glutamine expressed the same TLR2 levels as controls
      before treatment (4.9 +/- 3.5 rmfi vs. 4.3 +/- 1.9 rmfi, respectively; P = 0.9),
      at Day 6 (3.8 +/- 2.3 rmfi vs. 4.0 +/- 1.7 rmfi, respectively; P = 0.7) and at
      Day 14 (4.1 +/- 2.1 rfim vs. 4.6 +/- 1.9 rmfi, respectively; P = 0.08). TLR4
      levels were not significantly different between the groups before treatment: (1.1
      +/- 1 rmfi vs 0.9 +/- 0.1 rmfi respectively; P = 0.9), at Day 6 (1.1 +/- 1 rmfi
      vs. 0.7 +/- 0.4 rmfi respectively; P = 0.1) and at Day 14 (1.4 +/- 1.9 rmfi vs.
      1.0 +/- 0.6 rmfi respectively; P = 0.8). No differences in cell responses to TLR
      agonists were found between groups. TLR functionality studied by phagocytosis did
      not vary between groups. CONCLUSIONS: In trauma patients in the intensive care
      unit, TPN supplemented with glutamine does not improve the expression or the
      functionality of TLRs in peripheral blood monocytes. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT01250080.

PMID- 21184676
TI  - Incomplete concerted evolution and reproductive isolation at the rDNA locus
      uncovers nine cryptic species within Anopheles longirostris from Papua New
      Guinea.
AB  - BACKGROUND: Nuclear ribosomal DNA (rDNA) genes and transcribed spacers are highly
      utilized as taxonomic markers in metazoans despite the lack of a cohesive
      understanding of their evolution. Here we follow the evolution of the rDNA second
      internal transcribed spacer (ITS2) and the mitochondrial DNA cytochrome oxidase I
      subunit in the malaria mosquito Anopheles longirostris from Papua New Guinea
      (PNG). This morphospecies inhabits a variety of ecological environments
      indicating that it may comprise a complex of morphologically indistinguishable
      species. Using collections from over 70 sites in PNG, the mtDNA was assessed via
      direct DNA sequencing while the ITS2 was assessed at three levels - crude
      sequence variation through restriction digest, intragenomic copy variant
      organisation (homogenisation) through heteroduplex analysis and DNA sequencing
      via cloning. RESULTS: Genetic evaluation of over 300 individuals revealed that A.
      longirostris comprises eight ITS2 PCR-RFLP genotypes and nine ITS2 heteroduplex
      genotypes showing distinct copy variant organization profiles after PCR
      amplification. Seven of these nine genotypes were found to be sympatric with
      other genotypes. Phylogenetic analysis of cloned ITS2 PCR products and mtDNA COI
      confirmed all nine clades with evidence of reproductive isolation at the rDNA
      locus. Compensatory base changes in the ITS2 secondary structure or in
      pseudoknots were absent when closely related species were assessed. Individuals
      from each ITS2 genotype showed the same copy variant heteroduplex profile
      suggesting that the rDNA array is fixed within each genotype. CONCLUSION: The
      centromere-proximal position of the rDNA array in Anopheles mosquitoes has
      probably reduced interchromosomal recombination leaving intrachromosomal events
      responsible for the observed pattern of concerted evolution we see in these
      mosquitoes. The stability of these intragenomic ITS2 copy variants within
      individuals and interbreeding populations suggests that rDNA is moving as a
      single evolutionary unit through natural populations to fixation and has provided
      a complementary diagnostic tool to the restriction digest for studying genetic
      discontinuities and species boundaries. In this, the utility of the ITS2 as a
      universal taxonomic marker is probably contingent on several factors pertaining
      to spacer dimensions and the genomic location of the rDNA array with respect to
      recombination and proximity to regions potentially under selection.

PMID- 21184678
TI  - Turning around an ailing district hospital: a realist evaluation of strategic
      changes at Ho Municipal Hospital (Ghana).
AB  - BACKGROUND: There is a growing consensus that linear approaches to improving the
      performance of health workers and health care organisations may only obtain short
      term results. An alternative approach premised on the principle of human resource
      management described as a form of 'High commitment management', builds upon a
      bundles of balanced practices. This has been shown to contribute to better
      organisational performance. This paper illustrates an intervention and outcome of
      high commitment management (HiCom) at an urban hospital in Ghana. Few studies
      have shown how HiCom management might contribute to better performance of health
      services and in particular of hospitals in low and middle-income settings.
      METHODS: A realist case study design was used to analyse how specific management
      practices might contribute to improving the performance of an urban district
      hospital in Ho, Volta Region, in Ghana. Mixed methods were used to collect data,
      including document review, in-depth interviews, group discussions, observations
      and a review of routine health information. RESULTS: At Ho Municipal Hospital,
      the management team dealt with the crisis engulfing the ailing urban district
      hospital by building an alliance between hospital staff to generate a sense of
      ownership with a focus around participative problem analysis. The creation of an
      alliance led to improving staff morale and attitude, and contributed also to
      improvements in the infrastructure and equipment. This in turn had a positive
      impact on the revenue generating capacity of the hospital. The quick turn around
      in the state of this hospital showed that change was indeed possible, a factor
      that greatly motivated the staff.In a second step, the management team initiated
      the development of a strategic plan for the hospital to maintain the dynamics of
      change. This was undertaken through participative methods and sustained earlier
      staff involvement, empowerment and feelings of reciprocity. We found that these
      factors acted as the core mechanisms underlying the changes taking place at Ho
      Municipal Hospital. CONCLUSIONS: This study shows how a hospital management team
      in Ghana succeeded in resuscitating an ailing hospital. Their high commitment
      management approach led to the active involvement and empowerment of staff. It
      also showed how a realist evaluation approach such as this, could be used in the
      research of the management of health care organisations to explain how management
      interventions may or may not work.

PMID- 21184677
TI  - Primate-specific evolution of noncoding element insertion into PLA2G4C and human
      preterm birth.
AB  - BACKGROUND: The onset of birth in humans, like other apes, differs from non
      primate mammals in its endocrine physiology. We hypothesize that higher primate
      specific gene evolution may lead to these differences and target genes involved
      in human preterm birth, an area of global health significance. METHODS: We
      performed a comparative genomics screen of highly conserved noncoding elements
      and identified PLA2G4C, a phospholipase A isoform involved in prostaglandin
      biosynthesis as human accelerated. To examine whether this gene demonstrating
      primate-specific evolution was associated with birth timing, we genotyped and
      analyzed 8 common single nucleotide polymorphisms (SNPs) in PLA2G4C in US
      Hispanic (n = 73 preterm, 292 control), US White (n = 147 preterm, 157 control)
      and US Black (n = 79 preterm, 166 control) mothers. RESULTS: Detailed structural
      and phylogenic analysis of PLA2G4C suggested a short genomic element within the
      gene duplicated from a paralogous highly conserved element on chromosome 1
      specifically in primates. SNPs rs8110925 and rs2307276 in US Hispanics and
      rs11564620 in US Whites were significant after correcting for multiple tests (p <
      0.006). Additionally, rs11564620 (Thr360Pro) was associated with increased
      metabolite levels of the prostaglandin thromboxane in healthy individuals (p =
      0.02), suggesting this variant may affect PLA2G4C activity. CONCLUSIONS: Our
      findings suggest that variation in PLA2G4C may influence preterm birth risk by
      increasing levels of prostaglandins, which are known to regulate labor.

PMID- 21184679
TI  - Early childhood caries in preschool children of Kosovo - a serious public health
      problem.
AB  - BACKGROUND: Even though it has been widely studied, early childhood caries (ECC)
      remains a serious public health problem, especially in countries where there is
      no national program of oral health assessment and no genuine primary oral health
      care, such as in Kosovo. The purpose of this study was to assess the prevalence
      of ECC and analyze caries risk factors. METHODS: The subjects were 1,008
      preschool children, selected by stratified random cluster sampling, in the
      municipality of Prishtina, capital of Kosovo. Data were collected through
      clinical examination and interviews. Dmft data were recorded according to WHO
      criteria. Bacterial examination (CRT bacteria test) and plaque test of Greene
      Vermillion were used. RESULTS: The mean dmft of preschool children was found to
      be 5.8. The prevalence of ECC was 17.36%, with a mean dmft of 11 +/- 3.6.
      Streptococcus mutans prevalence in ECC children was 98%. A significant
      correlation between dmft and S mutans counts (>=105 CFU/mL saliva) was
      demonstrated. A correlation was also found between daily sweets consumption and
      dmft in children with ECC (P < 0.001). Comparing the dmft of ECC children and
      duration of bottle feeding showed a statistical correlation (P < 0.001). The mean
      plaque test was 1.52. None of the examined children had ever used fluoride.
      CONCLUSION: The prevalence of ECC was high among preschool children in the
      municipality of Kosovo. We recommend increasing parents' knowledge of proper
      feeding habits and oral health practices, and increasing preschool children's
      accessibility to dental services.

PMID- 21184680
TI  - The combined effect of smoking tobacco and drinking alcohol on cause-specific
      mortality: a 30 year cohort study.
AB  - BACKGROUND: Smoking and consuming alcohol are both related to increased mortality
      risk. Their combined effects on cause-specific mortality were investigated in a
      prospective cohort study. METHODS: Participants were 5771 men aged 35-64,
      recruited during 1970-73 from various workplaces in Scotland. Data were obtained
      from a questionnaire and a screening examination. Causes of death were all cause,
      coronary heart disease (CHD), stroke, alcohol-related, respiratory and smoking
      related cancer. Participants were divided into nine groups according to their
      smoking status (never, ex or current) and reported weekly drinking (none, 1-14
      units and 15 or more). Cox proportional hazards models were used to obtain
      relative rates of mortality, adjusted for age and other risk factors. RESULTS: In
      30 years of follow-up, 3083 men (53.4%) died. Compared with never smokers who did
      not drink, men who both smoked and drank 15+ units/week had the highest all-cause
      mortality (relative rate = 2.71 (95% confidence interval 2.31-3.19)). Relative
      rates for CHD mortality were high for current smokers, with a possible protective
      effect of some alcohol consumption in never smokers. Stroke mortality increased
      with both smoking and alcohol consumption. Smoking affected respiratory mortality
      with little effect of alcohol. Adjusting for a wide range of confounders
      attenuated the relative rates but the effects of alcohol and smoking still
      remained. Premature mortality was particularly high in smokers who drank 15 or
      more units, with a quarter of the men not surviving to age 65. 30% of men with
      manual occupations both smoked and drank 15+ units/week compared with only 13%
      with non-manual ones. CONCLUSIONS: Smoking and drinking 15+ units/week was the
      riskiest behaviour for all causes of death.

PMID- 21184681
TI  - Increased incidence of glucose disorders during pregnancy is not explained by pre
      pregnancy obesity in London, Canada.
AB  - BACKGROUND: The increasing incidence of impaired glucose tolerance (IGT),
      gestational diabetes (GDM) and type 2 diabetes (T2D) during pregnancy was
      hypothesized to be associated with increases in pre-pregnancy body mass index
      (BMI). The aims were to 1) determine the prevalence of IGT/GDM/T2 D over a 10
      year period; 2) examine the relationship between maternal overweight/obesity and
      IGT/GDM/T2D; and 3) examine the extent to which maternal metabolic complications
      impact maternal and fetal pregnancy outcomes. METHODS: Data arose from a
      perinatal database which contains maternal characteristics and perinatal outcome
      for all singleton infants born in London, Canada between January 1, 2000 and
      December 31, 2009. Univariable and multivariable odds ratios (OR) were estimated
      using logistic regression with IGT/GDM/T2 D being the outcome of interest.
      RESULTS: A total of 36,597 women were included in the analyses. Population
      incidence of IGT, GDM and T2 D rose from 0.7%, 2.9% and 0.5% in 2000 to 1.2%,
      4.2% and 0.9% in 2009. The univariable OR for IGT, GDM and T2 D were 1.65, 1.52
      and 2.06, respectively, over the ten year period. After controlling for maternal
      age, parity and pre-pregnancy BMI the OR did not decrease. Although there was a
      positive relationship between pre-pregnancy BMI and prevalence of IGT/GDM/T2 D,
      this did not explain the time trends in the latter. Diagnosis of IGT/GDM/T2 D
      increased the risk of having an Apgar score <7 at 5 minutes, which was partially
      explained by gestational hypertension, high placental ratio, gestational age and
      large for gestational age babies. CONCLUSIONS: We found a significant increase in
      the incidence of IGT/GDM/T2 D for the decade between 2000-2009 which was not
      explained by rising prevalence of maternal overweight/obesity.

PMID- 21184682
TI  - Costs of receipt and donation of ejaculates in a simultaneous hermaphrodite.
AB  - BACKGROUND: Sexual conflicts between mating partners can strongly impact the
      evolutionary trajectories of species. This impact is determined by the balance
      between the costs and benefits of mating. However, due to sex-specific costs it
      is unclear how costs compare between males and females. Simultaneous
      hermaphrodites offer a unique opportunity to determine such costs, since both
      genders are expressed concurrently. By limiting copulation of focal individuals
      in pairs of pond snails (Lymnaea stagnalis) to either the male role or the female
      role, we were able to compare the fecundity of single sex individuals with paired
      hermaphrodites and non-copulants. Additionally, we examined the investment in
      sperm and seminal fluid of donors towards feminized snails and hermaphrodites.
      RESULTS: Compared to non-mating focal snails, reciprocating individuals as well
      as male and female copulants experienced a significant fecundity reduction (~40%)
      after, on average, 3.07 +/- 0.12 copulations in their allowed roles (for donors
      2.98 +/- 0.16 copulations and for recipients 3.14 +/- 0.12 copulations). In a
      single copulation, significantly more sperm was donated to partners that were
      restricted to mating in the female role than to hermaphrodites, while seminal
      fluid transfer was unaffected by recipient type. CONCLUSIONS: Our data indicate
      that the costs of mating in both sex functions are high in L. stagnalis. This
      conclusion is based on fecundity data collected separately for male and female
      copulants. Male mating costs result from investment in expensive ejaculates,
      composed of sperm and seminal fluid. For female copulants, fecundity reduction
      correlated with transferred sperm numbers in the first copulation, while
      differences in transferred quantities of seminal fluid were not detected. These
      findings may point toward a "sperm effect" as a novel feature of pond snail
      reproductive ecology. In conclusion, sex allocation and sexual conflict both
      contribute to decreased female fecundity in pond snails.

PMID- 21184683
TI  - Hydrogen inhalation ameliorates ventilator-induced lung injury.
AB  - INTRODUCTION: Mechanical ventilation (MV) can provoke oxidative stress and an
      inflammatory response, and subsequently cause ventilator-induced lung injury
      (VILI), a major cause of mortality and morbidity of patients in the intensive
      care unit. Inhaled hydrogen can act as an antioxidant and may be useful as a
      novel therapeutic gas. We hypothesized that, owing to its antioxidant and anti
      inflammatory properties, inhaled hydrogen therapy could ameliorate VILI. METHODS:
      VILI was generated in male C57BL6 mice by performing a tracheostomy and placing
      the mice on a mechanical ventilator (tidal volume of 30 ml/kg without positive
      end-expiratory pressure, FiO(2) 0.21). The mice were randomly assigned to
      treatment groups and subjected to VILI with delivery of either 2% nitrogen or 2%
      hydrogen in air. Sham animals were given same gas treatments for two hours (n = 8
      for each group). The effects of VILI induced by less invasive and longer exposure
      to MV (tidal volume of 10 ml/kg, 5 hours, FiO(2) 0.21) were also investigated (n
      = 6 for each group). Lung injury score, wet/dry ratio, arterial oxygen tension,
      oxidative injury, and expression of pro-inflammatory mediators and apoptotic
      genes were assessed at the endpoint of two hours using the high-tidal volume
      protocol. Gas exchange and apoptosis were assessed at the endpoint of five hours
      using the low-tidal volume protocol. RESULTS: Ventilation (30 ml/kg) with 2%
      nitrogen in air for 2 hours resulted in deterioration of lung function, increased
      lung edema, and infiltration of inflammatory cells. In contrast, ventilation with
      2% hydrogen in air significantly ameliorated these acute lung injuries. Hydrogen
      treatment significantly inhibited upregulation of the mRNAs for pro-inflammatory
      mediators and induced antiapoptotic genes. In the lungs treated with hydrogen,
      there was less malondialdehyde compared with lungs treated with nitrogen.
      Similarly, longer exposure to mechanical ventilation within lower tidal volume
      (10 mg/kg, five hours) caused lung injury including bronchial epithelial
      apoptosis. Hydrogen improved gas exchange and reduced VILI-induced apoptosis.
      CONCLUSIONS: Inhaled hydrogen gas effectively reduced VILI-associated
      inflammatory responses, at both a local and systemic level, via its antioxidant,
      anti-inflammatory and antiapoptotic effects.

PMID- 21184684
TI  - Implementation of a reference standard and proficiency testing programme by the
      World Wide Antimalarial Resistance Network (WWARN).
AB  - BACKGROUND: The Worldwide Antimalarial Resistance Network (WWARN) is a global
      collaboration to support the objective that anyone affected by malaria receives
      effective and safe drug treatment. The Pharmacology module aims to inform optimal
      anti-malarial drug selection. There is an urgent need to define the drug exposure
      - effect relationship for most anti-malarial drugs. Few anti-malarials have had
      their therapeutic blood concentration levels defined. One of the main challenges
      in assessing safety and efficacy data in relation to drug concentrations is the
      comparability of data generated from different laboratories. To explain
      differences in anti-malarial pharmacokinetics in studies with different
      measurement laboratories it is necessary to confirm the accuracy of the assay
      methods. This requires the establishment of an external quality assurance process
      to assure results that can be compared. This paper describes this process.
      METHODS: The pharmacology module of WWARN has established a quality
      assurance/quality control (QA/QC) programme consisting of two separate
      components:1. A proficiency testing programme where blank human plasma spiked
      with certified reference material (CRM) in different concentrations is sent out
      to participating bioanalytical laboratories.2. A certified reference standard
      programme where accurately weighed amounts of certified anti-malarial reference
      standards, metabolites, and internal standards are sent to participating
      bioanalytical and in vitro laboratories. CONCLUSION: The proficiency testing
      programme is designed as a cooperative effort to help participating laboratories
      assess their ability to carry out drug analysis, resolve any potential problem
      areas and to improve their results - and, in so doing, to improve the quality of
      anti-malarial pharmacokinetic data published and shared with WWARN.By utilizing
      the same source of standards for all laboratories, it is possible to minimize
      bias arising from poor quality reference standards. By providing anti-malarial
      drug standards from a central point, it is possible to lower the cost of these
      standards.

PMID- 21184685
TI  - The checkpointkinase 2 (CHK2) 1100delC germ line mutation is not associated with
      the development of squamous cell carcinoma of the head and neck (SCCHN).
AB  - BACKGROUND: The checkpointkinase 2 (CHK2) is part of the highly conserved ATM
      CHK2 signaling pathway, which is activated in response to DNA damage, in
      particular after double strand breaks which can be caused by carcinogens like
      smoking. After induction of downstream targets, e.g. the tumor suppressor p53,
      its activation leads to cell cycle arrest and apoptosis. Recently, the presence
      of CHK2 germ line mutations, primarily the 1100delC variant, has been reported to
      be involved in carcinogenesis. The CHK2 1100delC variant results in a truncated
      protein which is instable and inactive. Carriers of this variant have been shown
      to have an increased risk to develop breast cancer and probably also other
      tumors. Our purpose was to investigate the role of CHK2 germ line mutations in
      patients with squamous cell carcinoma of the head and neck (SCCHN). MATERIALS AND
      METHODS: We investigated 91 patients suffering from SCCHN including all tumor
      sites (oropharynx, hypopharynx, larynx) for the presence of the germ line
      mutation 1100delC by direct sequence analysis. Patients were characterized by
      their tumor localization, tumor stage, age, the presence of additional malignant
      tumors and predisposing carcinogens (smoking, alcohol abuse). RESULTS: None of
      the patients, independently of the tumor site, age, the abuse of predisposing
      carcinogens, or the presence of other kinds of tumors, carried the CHK2 1100delC
      variant. CONCLUSIONS: The germ line CHK2 1100delC variant does not seem to have a
      major impact on the development of SCCHN.

PMID- 21184686
TI  - Quantitative analysis of mRNA translation in mammalian spermatogenic cells with
      sucrose and Nycodenz gradients.
AB  - BACKGROUND: Developmental and global regulation of mRNA translation plays a major
      role in regulating gene expression in mammalian spermatogenic cells. Sucrose
      gradients are widely used to analyze mRNA translation. Unfortunately, the
      information from sucrose gradient experiments is often compromised by the absence
      of quantification and absorbance tracings, and confusion about the basic
      properties of sucrose gradients. METHODS: The Additional Materials contain
      detailed protocols for the preparation and analysis of sucrose and Nycodenz
      gradients, obtaining absorbance tracings of sucrose gradients, aligning tracings
      and fractions, and extraction of equal proportions of RNA from all fractions.
      RESULTS: The techniques described here have produced consistent measurements
      despite changes in personnel and minor variations in RNA extraction, gradient
      analysis, and mRNA quantification, and describes for the first time potential
      problems in using gradients to analyze mRNA translation in purified spermatogenic
      cells. CONCLUSIONS: Accurate quantification of the proportion of polysomal mRNA
      is useful in comparing translational activity at different developmental stages,
      different mRNAs, different techniques and different laboratories. The techniques
      described here are sufficiently accurate to elucidate the contributions of
      multiple regulatory elements of variable strength in regulating translation of
      the sperm mitochondria associated cysteine-rich protein (Smcp) mRNA in transgenic
      mice.

PMID- 21184687
TI  - Nutritional related cardiovascular risk factors in patients with coronary artery
      disease in Iran: a case-control study.
AB  - BACKGROUND AND AIMS: There are limited findings available on coronary artery
      disease (CAD) risk factors and nutritional pattern of CAD patients in Iran. The
      purpose of this study was to compare nutritional-related risk factors of CAD
      patients with that of matched controls. METHODS: In a case-control design,
      dietary patterns and CAD risk factors of 108 documented patients (determined by
      cardiac catheterization showing greater than 70% stenosis or established
      myocardial infarction) whom were admitted to coronary care units (CCU) of Ahvaz
      teaching hospitals were compared with that of 108 gender- and age-matched
      subjects of normal cardiac catheterization (lesser than 40% stenosis). Measured
      variables consisted of blood lipid profile, smoking habits, dietary patterns,
      anthropometric indices and blood pressure levels. RESULTS: Almost all patients
      had hypertriglyceridemia and high LDL-C levels. Odds ratios (CI 95%) for
      consuming fish, tea, vegetable oils were 0.55(0.31-0.91), 0.3(0.15-0.65),
      0.23(0.13-0.42), respectively. However, consumption of hydrogenated fats, and
      full-fat yoghurt was associated with higher CAD risk (OR = 2.12(1.23-3.64) and
      2.35(1.32-4.18), respectively. Patients' serum lipid profiles, sugar
      concentrations, and blood pressure levels were significantly higher than defined
      cut-off points of the known risk factors. Considerable numbers of the control
      group also showed high levels of the known risk factors. CONCLUSIONS: Consumption
      of fish, tea and vegetable oils shown to have protective effect on CAD while full
      fat yoghurt and hydrogenated fats increase the risk of CAD. Moreover, CAD
      patients obviously have higher blood lipids and sugar concentrations, blood
      pressure, body fat percent and BMI levels compared with their matched
      counterparts. We need to define specific local cut-off points with more practical
      criteria to detect CAD patients.

PMID- 21184688
TI  - RISCI--Repeat Induced Sequence Changes Identifier: a comprehensive, comparative
      genomics-based, in silico subtractive hybridization pipeline to identify repeat
      induced sequence changes in closely related genomes.
AB  - BACKGROUND: The availability of multiple whole genome sequences has facilitated
      in silico identification of fixed and polymorphic transposable elements (TE).
      Whereas polymorphic loci serve as makers for phylogenetic and forensic analysis,
      fixed species-specific transposon insertions, when compared to orthologous loci
      in other closely related species, may give insights into their evolutionary
      significance. Besides, TE insertions are not isolated events and are frequently
      associated with subtle sequence changes concurrent with insertion or post
      insertion. These include duplication of target site, 3' and 5' flank
      transduction, deletion of the target locus, 5' truncation or partial deletion and
      inversion of the transposon, and post insertion changes like inter or intra
      element recombination, disruption etc. Although such changes have been studied
      independently, no automated platform to identify differential transposon
      insertions and the associated array of sequence changes in genomes of the same or
      closely related species is available till date. To this end, we have designed
      RISCI - 'Repeat Induced Sequence Changes Identifier' - a comprehensive,
      comparative genomics-based, in silico subtractive hybridization pipeline to
      identify differential transposon insertions and associated sequence changes using
      specific alignment signatures, which may then be examined for their downstream
      effects. RESULTS: We showcase the utility of RISCI by comparing full length and
      truncated L1HS and AluYa5 retrotransposons in the reference human genome with the
      chimpanzee genome and the alternate human assemblies (Celera and HuRef).
      Comparison of the reference human genome with alternate human assemblies using
      RISCI predicts 14 novel polymorphisms in full length L1HS, 24 in truncated L1HS
      and 140 novel polymorphisms in AluYa5 insertions, besides several insertion and
      post insertion changes. We present comparison with two previous studies to show
      that RISCI predictions are broadly in agreement with earlier reports. We also
      demonstrate its versatility by comparing various strains of Mycobacterium
      tuberculosis for IS 6100 insertion polymorphism. CONCLUSIONS: RISCI combines
      comparative genomics with subtractive hybridization, inferring changes only when
      exclusive to one of the two genomes being compared. The pipeline is generic and
      may be applied to most transposons and to any two or more genomes sharing high
      sequence similarity. Such comparisons, when performed on a larger scale, may pull
      out a few critical events, which may have seeded the divergence between the two
      species under comparison.

PMID- 21184689
TI  - Long term outcome of adolescent and adult patients with pineal parenchymal tumors
      treated with fractionated radiotherapy between 1982 and 2003--a single
      institution's experience.
AB  - BACKGROUND: To evaluate the effectivity of fractionated radiotherapy in
      adolescent and adult patients with pineal parenchymal tumors (PPT). METHODS:
      Between 1982 and 2003, 14 patients with PPTs were treated with fractionated
      radiotherapy. 4 patients had a pineocytoma (PC), one a PPT with intermediate
      differentiation (PPTID) and 9 patients a pineoblastoma (PB), 2 of which were
      recurrences. All patients underwent radiotherapy on the primary tumor site with a
      median total dose of 54 Gy. In 9 patients with primary PB treatment included
      whole brain irradiation (3 patients) or irradiation of the craniospinal axis (6
      patients) with a median total dose of 35 Gy. RESULTS: Median follow-up was 123
      months in the PC patients and 109 months in the patients with primary PB. 7
      patients were free from relapse at the end of follow-up. One PC patient died from
      spinal seeding. Among 5 PB patients treated with radiotherapy without
      chemotherapy, 3 developed local or spinal tumor recurrence. Both patients treated
      for PB recurrences died. The patient with PPTID is free of disease 7 years after
      radiotherapy. CONCLUSION: Local radiotherapy seems to be effective in patients
      with PC and some PPTIDs. Diagnosis and treatment of patients with more aggressive
      variants of PPTIDs as well as treatment of PB needs to be further improved, since
      local and spinal failure even despite craniospinal irradiation (CSI) is common.
      As PPT are very rare tumors, treatment within multi-institutional trials remains
      necessary.

PMID- 21184690
TI  - Identification of differentially expressed genes induced by Bamboo mosaic virus
      infection in Nicotiana benthamiana by cDNA-amplified fragment length
      polymorphism.
AB  - BACKGROUND: The genes of plants can be up- or down-regulated during viral
      infection to influence the replication of viruses. Identification of these
      differentially expressed genes could shed light on the defense systems employed
      by plants and the mechanisms involved in the adaption of viruses to plant cells.
      Differential gene expression in Nicotiana benthamiana plants in response to
      infection with Bamboo mosaic virus (BaMV) was revealed using cDNA-amplified
      fragment length polymorphism (AFLP). RESULTS: Following inoculation with BaMV, N.
      benthamiana displayed differential gene expression in response to the infection.
      Isolation, cloning, and sequencing analysis using cDNA-AFLP furnished 90 cDNA
      fragments with eight pairs of selective primers. Fifteen randomly selected genes
      were used for a combined virus-induced gene silencing (VIGS) knockdown
      experiment, using BaMV infection to investigate the roles played by these genes
      during viral infection, specifically addressing the means by which these genes
      influence the accumulation of BaMV protein. Nine of the 15 genes showed either a
      positive or a negative influence on the accumulation of BaMV protein. Six
      knockdown plants showed an increase in the accumulation of BaMV, suggesting that
      they played a role in the resistance to viral infection, while three plants
      showed a reduction in coat protein, indicating a positive influence on the
      accumulation of BaMV in plants. An interesting observation was that eight of the
      nine plants showing an increase in BaMV coat protein were associated with cell
      rescue, defense, death, aging, signal transduction, and energy production.
      CONCLUSIONS: This study reports an efficient and straightforward method for the
      identification of host genes involved in viral infection. We succeeded in
      establishing a cDNA-AFLP system to help track changes in gene expression patterns
      in N. benthamiana plants when infected with BaMV. The combination of both DNA
      AFLP and VIGS methodologies made it possible to screen a large number of genes
      and identify those associated with infections of plant viruses. In this report, 9
      of the 15 analyzed genes exhibited either a positive or a negative influence on
      the accumulation of BaMV in N. benthamiana plants.

PMID- 21184691
TI  - The reality of using primaquine.
AB  - BACKGROUND: Primaquine is currently the only medication used for radical cure of
      Plasmodium vivax infection. Unfortunately, its use is not without risk. Patients
      with glucose-6-phosphate dehydrogenase (G6PD) deficiency have an increased
      susceptibility to haemolysis when given primaquine. This potentially fatal
      clinical syndrome can be avoided if patients are tested for G6PD deficiency and
      adequately informed before being treated. CASE PRESENTATION: A 35-year old male
      presented to our clinic on the Thai-Burmese border with a history and clinical
      examination consistent with intravascular haemolysis. The patient had been
      prescribed primaquine and chloroquine four days earlier for a P. vivax infection.
      The medication instructions had not been given in a language understood by the
      patient and he had not been tested for G6PD deficiency. The patient was not only
      G6PD deficient but misunderstood the instructions and took all his primaquine
      tablets together. With appropriate treatment the patient recovered and was
      discharged home a week later. CONCLUSIONS: Whilst primaquine remains the drug of
      choice to eradicate hypnozoites and control P. vivax transmission, the risks
      associated with its use must be minimized during its deployment. In areas where
      P. vivax exists, patients should be tested for G6PD deficiency and adequately
      informed before administration of primaquine.

PMID- 21184692
TI  - Cognitive and psychosocial development of HIV pediatric patients receiving highly
      active anti-retroviral therapy: a case-control study.
AB  - BACKGROUND: The psychosocial development of pediatric HIV patients has not been
      extensively evaluated. The study objectives were to evaluate whether emotional
      and social functions are differentially associated with HIV-related
      complications. METHODS: A matched case-control study design was conducted. The
      case group (n = 20) consisted of vertically infected children with HIV (aged 3-18
      years) receiving HAART in Greece. Each case was matched with two randomly
      selected healthy controls from a school-based population. CNS imaging and
      clinical findings were used to identify patients with HIV-related neuroimaging
      abnormalities. The Wechsler Intelligence Scale III and Griffiths Mental Abilities
      Scales were applied to assess cognitive abilities. The age specific Strengths and
      Difficulties Questionnaire was used to evaluate emotional adjustment and social
      skills. The Fisher's exact test, student's t-test, and Wilcoxon rank sum test
      were used to compare categorical, continuous, and ordinal scores, respectively,
      of the above scales between groups. RESULTS: HIV patients without neuroimaging
      abnormalities did not differ from patients with neuroimaging abnormalities with
      respect to either age at HAART initiation (p = 0.306) or months of HAART
      treatment (p = 0.964). While HIV patients without neuroimaging abnormalities had
      similar cognitive development with their healthy peers, patients with
      neuroimaging abnormalities had lower mean General (p = 0.027) and Practical (p =
      0.042) Intelligence Quotient scores. HIV patients without neuroimaging
      abnormalities had an increased likelihood of both Abnormal Emotional Symptoms (p
      = 0.047) and Hyperactivity scores (p = 0.0009). In contrast, HIV patients with
      neuroimaging abnormalities had an increased likelihood of presenting with
      Abnormal Peer Problems (p = 0.033). CONCLUSIONS: HIV patients without
      neuroimaging abnormalities are more likely to experience maladjustment with
      respect to their emotional and activity spheres, while HIV patients with
      neuroimaging abnormalities are more likely to present with compromised social
      skills. Due to the limited sample size and age distribution of the study
      population, further studies should investigate the psychosocial development of
      pediatric HIV patients following the disclosure of their condition.

PMID- 21184693
TI  - Dedication to Manoel Pimentel Neto --1928-2010.
AB  - Dr Manoel Pimentel Neto's career as a researcher and adviser is recalled in this
      summary of his professional life. He adored his work, to which he dedicated
      himself fully as an exemplary public employee. In 1958, he graduated in
      veterinary medicine from the Rural University of Brazil (Universidade Rural do
      Brasil; URB), which today is the Rural Federal University of Rio de Janeiro
      (Universidade Federal Rural do Rio de Janeiro; UFRRJ). At that time, postgraduate
      training in different aspects of veterinary medicine did not exist. Dr Pimentel
      started his activities as a veterinary surgeon at the then Ministry of
      Agriculture, working on cattle health, and later on transferred to the National
      Department of Agricultural and Livestock Research (DNPA), which was the
      institution that evolved into the present-day EMBRAPA.

PMID- 21184694
TI  - Cryptosporidium infection in Brazil: implications for veterinary medicine and
      public health.
AB  - The aim of this review paper is to report the results of cryptosporidiosis
      research in Brazil, mainly its occurrence in animals and implications for
      veterinary medicine and public health. An increasing number of papers related to
      Cryptosporidium spp. infection in Brazil are available at national and
      international literature. The main focus described in these papers is the
      occurrence of Cryptosporidium spp. in food, environmental samples, in humans and
      several animal species, particularly birds, cattle, dogs and cats. Using
      molecular biology techniques, most Cryptosporidium species and genotypes
      identified in other countries have been described in Brazil. In mammals, there
      are descriptions of infection by C. bovis, C. canis, C. felis, C. meleagridis, C.
      parvum, and the cervine genotype; in birds, the following species and genotypes
      have been described: C. baileyi, C. galli, C. meleagridis, C. parvum and the
      avian genotypes I, II and III. Several species have been described in humans,
      such as C. parvum, C. hominis, and some species adapted to animal hosts such as
      C. canis, C. felis and C. meleagridis.

PMID- 21184695
TI  - Serological survey of Rickettsia sp. in horses and dogs in a non-endemic area in
      Brazil.
AB  - Brazilian Spotted Fever (BSF) is a lethal rickettsiosis in humans caused by the
      bacteria Rickettsia rickettsii, and is endemic in some areas of Brazil. Horses
      and dogs are part of the disease's life cycle and they may also serve as sentinel
      animals in epidemiological studies. The first human BSF case in the State of
      Parana was reported in 2005. The present study was conducted in the municipality
      of Almirante Tamandare, where no previous case of BSF was reported. Serum samples
      were collected from 71 horses and 20 dogs from nine properties in the area. Ticks
      were also collected from these animals. All farmers completed a questionnaire
      about their knowledge of BSF and animal health management. Serum samples were
      analyzed by indirect immunofluorescent-antibody assay (IFA) using R. rickettsii
      and R. parkeri as antigens. Ticks were analyzed by PCR for Rickettsia sp., and
      all of them were PCR-negative. Six horses (8.45%) and 4 dogs (20%) were
      identified as seropositive. Farmers were not aware of the correlation between the
      presence of ticks and risk of BSF. Although a non-endemic area, Almirante
      Tamandare is a vulnerable environment for BSF and effective tick control measures
      are required.

PMID- 21184696
TI  - Toxoplasma gondii: humoral and cellular immune response of BALB/c mice immunized
      via intranasal route with rTgROP2.
AB  - TgROP2 is an intracellular protein associated with rhoptries of Toxoplama gondii
      and an antigen component of a candidate vaccine for toxoplasmosis. The purpose of
      the present study was to evaluate the efficacy of rTgROP2 to stimulate humoral
      and cellular immune responses in BALB/c mice via intranasal injection. TgROP2
      partial coding sequence was (196-561) amplified by PCR from genomic T. gondii RH
      strain DNA and cloned into the pTrcHis expression vector. Escherichia coli
      Rosetta 2 cells transformed with pTrcHis-TgROP2 showed high levels (~1 mg.mL(-1))
      of recombinant protein after 4 hours of IPTG induction. Recombinant TgROP2
      exhibited an apparent Mr equal to 54 kDa. In order to test immunogenicity of the
      recombinant protein, 10 BALB/c mice received 10 ug of rROP2 protein + 10 ug of
      Quil-A via intranasal injection. Doses were administered at days 0, 21, and 42.
      Three animals were euthanized and used to evaluate cellular immune response on
      day 62. Five (50%) and two (20%) out of ten animals produced IgG (DO mean =
      0.307; cut-off = 0.240) and IgA (DO mean = 0.133, cut-off = 0.101), respectively,
      by ELISA on day 62. The proliferation of splenocytes revealed high stimulation
      index (SI) when co-cultured with 5, 10 and 15 ug.mL(-1) of rTgROP2. These results
      indicate that intranasal immunization with recombinant protein ROP2 plus Quil-A
      can elicit both cellular and humoral immune responses in BALB/c mice.

PMID- 21184697
TI  - Efficacy evaluation of a commercial neem cake for control of Haematobia irritans
      on Nelore cattle.
AB  - Much attention has been given to the development of botanical insecticides to
      provide effective natural control of cattle ectoparasites without harming
      animals, consumers, and environment. This study evaluated the efficacy of a
      commercial neem cake in controlling Haematobia irritans infestation on cattle.
      The study was conducted at the Embrapa Southeast Cattle Research Center (CPPSE),
      in Sao Carlos, SP, Brazil, from April to July 2008. The neem cake mixed in
      mineral salt in a 2% concentration was provided to 20 Nelore cows during nine
      weeks and had its efficacy evaluated by comparison of the infestation level
      against a control group. Fly infestations were recorded weekly by digital
      photographs of each animal from both groups and the number of flies was later
      counted in a computer-assisted image analyzer. Quantification of neem cake
      components by high-performance liquid chromatography revealed the presence of
      azadirachtin (421 mg.kg(-1)) and 3-tigloyl-azadirachtol (151 mg.kg(-1)) in the
      tested neem cake. Addition of the 2% neem cake reduced mineral salt intake in
      about 22%. The 2% neem cake treatment failed to reduce horn fly infestations on
      cattle during the 9-week study period.

PMID- 21184698
TI  - Seroprevalence of Rickettsia bellii and Rickettsia felis in dogs, Sao Jose dos
      Pinhais, State of Parana, Brazil.
AB  - Brazilian spotted fever (BSF) is a vector-borne zoonosis caused by Rickettsia
      rickettsii bacteria. Dogs can be host sentinels for this bacterium. The aim of
      the study was to determine the presence of antibodies against Rickettsia spp. in
      dogs from the city of Sao Jose dos Pinhais, State of Parana, Southern Brazil,
      where a human case of BSF was first reported in the state. Between February 2006
      and July 2007, serum samples from 364 dogs were collected and tested at 1:64
      dilutions by indirect immunofluorescence assay (IFA) against R. rickettsii and R.
      parkeri. All sera that reacted at least to one of Rickettsia species were tested
      against the six main Rickettsia species identified in Brazil: R. rickettsii, R.
      parkeri, R. bellii, R. rhipicephali, R. amblyommii and R. felis. Sixteen samples
      (4.4%) reacted to at least one Rickettsia species. Among positive animals, two
      dogs (15.5%) showed suggestive titers for R. bellii exposure. One sample had a
      homologous reaction to R. felis, a confirmed human pathogen. Although Rickettsia
      spp. circulation in dogs in the area studied may be considered at low prevalence,
      suggesting low risk of human infection, the present data demonstrate for the
      first time the exposure of dogs to R. bellii and R. felis in Southern Brazil.

PMID- 21184699
TI  - Occurrence of Theileria equi in horses raised in the Jaboticabal microregion, Sao
      Paulo State, Brazil.
AB  - Blood and serum samples from 170 horses raised in the Jaboticabal microregion,
      Sao Paulo State, Brazil, were collected and tested by microscopic examination of
      blood smears, indirect fluorescent antibody test (IFAT) and nested polymerase
      chain reaction (nPCR) for Theileria equi infections. The association among the
      test results was verified by the McNemar test. During the examination of thin
      blood smears, parasites were detected in six (3.52%) horses. Anti-T. equi
      antibodies were detected in 100% sera samples, with titers ranging between 1:80
      and 1:5120. The nPCR based on the T. equi merozoite antigen gene (EMA-1) allowed
      the visualization of species-specific amplified product in 108 (63.53%) horses.
      All six samples judged positive microscopically were also positive for nPCR.
      Statistical analysis indicated general disagreement (p < 0.0001) between IFAT and
      nPCR; IFAT and blood smear; and nPCR and blood smear on the detection of parasite
      carriers. The results of the present study indicate that T. equi is widely spread
      among horses in the Jaboticabal microregion, Northeast region of Sao Paulo State,
      Brazil.

PMID- 21184700
TI  - Sandflies (Psychodidae: Phlebotominae) survey in an urban transmission area of
      visceral leishmaniasis, Northeastern Brazil.
AB  - Visceral leishmaniasis (VL) is a major public health challenge in Brazil,
      especially in states where it is endemic. The aim of this study was to
      investigate the relationship of sand fly population density with environmental
      variables (temperature, rainfall and relative humidity) in urban areas of the
      city of Mossoro, Rio Grande do Norte, Northeastern Brazil. Sand flies were
      captured with Center Disease Control (CDC) traps installed monthly in the intra
      and peridomicile of three houses. Data analysis was based on the chi-square test
      and linear regression. A total of 7,347 sand flies were captured, being 93.85%
      Lutzomyia longipalpis and 6.15% Lutzomyia evandroi. Sand flies were more commonly
      found in the peridomicile and there was no difference between the number of males
      and females. The variables rainy season as well as relative humidity and
      rainfall, alone or together, did not have an effect on sand fly population
      density. However, high temperatures had a negative effect. The study of the
      behavior of sand flies in specific units of endemic areas can provide input to
      public health authorities for planning appropriate VL vector control measures.

PMID- 21184701
TI  - Toxoplasma gondii: diagnosis of experimental and natural infection in pigeons
      (Columba livia) by serological, biological and molecular techniques.
AB  - This study aimed to diagnose experimental and natural Toxoplasma gondii infection
      in pigeons (Columba livia) by serological, biological and molecular techniques.
      Twelve pigeons, free of infection, were inoculated with 50 sporulated oocysts of
      T. gondii (VEG sample) and four remained uninfected controls. Four birds (three
      infected and one control) were euthanized at 15, 30, 45 and 60 days post
      infection (dpi), and their tissues were used to perform a bioassay in mice and
      nested-PCR using B1 gene as target. Blood was obtained weekly and it was tested
      for the presence of anti-T. gondii antibodies by the indirect fluorescent
      antibody test (IFAT) and modified agglutination test (MAT). Seven (58.3%) out of
      12 inoculated pigeons were positive by serological techniques and titers ranged
      between 1:40 and 1:5120 by MAT and between 1:512 and 1:4096 by IFAT. Complete
      agreement was seen between the results obtained by serological techniques and
      nested-PCR in seven positive birds. In the bioassay in mice, five (41.7%) out of
      12 pigeons inoculated were positive to T. gondii. Only one pigeon died at 23 dpi
      due to toxoplasmosis. A second study with free-living pigeons was performed for
      detection of anti-T. gondii antibodies. Birds were captured in the municipalities
      of Sao Paulo, Ibiuna and Sorocaba, Sao Paulo State, Southeastern Brazil. All 126
      free-living birds were negative to anti-T. gondii antibodies by MAT (titer <
      1:5). Bioassays were performed in mice with tissues from all captured birds and
      T. gondii was not isolated in any pigeon.

PMID- 21184702
TI  - Ticks on birds in a forest fragment of Brazilian cerrado (savanna) in the
      municipality of Uberlandia, State of Minas Gerais, Brazil.
AB  - This is a report of tick species, parasite prevalence and infestation intensity
      of birds in a forest fragment (18 degrees  56' 57'' S and 48 degrees  12' 14'' W)
      within the Brazilian cerrado (savanna), in the municipality of Uberlandia, State
      of Minas Gerais, Brazil. A total of 162 birds from 26 species were captured. One
      adult tick, 296 larvae and 67 nymphs were found on passerine birds. Of these, it
      was identified 31 larvae and 27 nymphs of Amblyomma longirostre, 17 nymphs of A.
      nodosum, one A. cajennense larvae and one male of Rhipicephalus sanguineus. All
      other ticks were identified as Amblyomma sp. larvae (n = 264) or nymphs (n = 26).
      Overall tick infestation intensity and prevalence were 4.32 ticks/infested bird
      and 52%, respectively. Sampling of host-seeking ticks on the ground within the
      forest during a two-year period showed only five Amblyomma sp. nymphs and one
      adult male of A. nodosum whereas a search for ticks on domestic animals (cattle,
      horses and dogs) found Rhipicephalus (Boophilus) microplus ticks. Although
      identification was possible in only 27% of bird ticks there seemed to be no
      correlation between environmental and domestic animal and bird infestation. It
      can be assumed that bird infestation may occur above the ground or at specific
      sites not sampled.

PMID- 21184703
TI  - Occurrence and molecular characterization of Cryptosporidium spp. isolated from
      domestic animals in a rural area surrounding Atlantic dry forest fragments in
      Teodoro Sampaio municipality, State of Sao Paulo, Brazil.
AB  - The aim of this study was to assess the occurrence of Cryptosporidium in domestic
      animals in rural properties surrounding rain forest fragments within the
      municipality of Teodoro Sampaio, southeastern Brazil. Conventional sucrose
      flotation method followed by molecular characterization of the parasites by
      sequencing PCR products amplified from SSU rRNA gene were used. Stool samples
      were collected from domestic animals raised as pets and livestock in all rural
      properties surrounding three forest fragments. Samples from cattle (197), equine
      (63), pigs (25), sheep (11), and dogs (28) were collected from 98 rural
      properties. The frequency of occurrence of Cryptosporidium within each animal
      species was 3.0% (6/197) among cattle and 10.7% (3/28) among dogs.
      Cryptosporidium was not detected in stool samples from equine, sheep, and pigs.
      All sequences obtained from the six samples of calves showed molecular identity
      with Cryptosporidium andersoni while all sequences from dog samples were similar
      to C. canis. The frequency of occurrence of Cryptosporidium in these domestic
      animal species was low. The absence of C. parvum in the present study suggests
      that the zoonotic cycle of cryptosporidiosis may not be relevant in the region
      studied. The presence of Cryptosporidium species seldom described in humans may
      be, otherwise, important for the wild fauna as these animals are a source of
      infection and dissemination of this protozoan to other animal species. The impact
      and magnitude of infection by C. andersoni in wild ruminants and C. canis in wild
      canids have to be assessed in future studies to better understand the actual
      importance of these species in this region.

PMID- 21184704
TI  - Seroprevalence of Toxoplasma gondii infection in swine matrices in Nova Mutum and
      Diamantino, Mato Grosso, Brazil.
AB  - This report aimed to assess the seroprevalence of Toxoplasma gondii infection in
      708 swine matrices in Nova Mutum and Diamantino in the state of Mato Grosso,
      Central-West Brazil. Serum samples were examined by indirect fluorescent antibody
      test (IFAT). It was found a seroprevalence of 12.8%, considering titers >= 64.
      Therefore, the data reinforce the need for appropriate management of swine
      raising to minimize the risk of infection of pigs with T. gondii.

PMID- 21184705
TI  - Occurrence of Leishmania (Leishmania) chagasi in a domestic cat (Felis catus) in
      Andradina, Sao Paulo, Brazil: case report.
AB  - This work describes natural infection by Leishmania in a domestic cat where
      amastigote forms of the parasite were observed in the popliteal lymph node
      imprint. Positive and negative serological reactions were observed by enzyme
      linked immunosorbent assay (ELISA) and indirect immunofluorescence assay (IFA),
      respectively. Polymerase chain reaction (PCR) revealed that the nucleotide
      sequence of the sample was identical to Leishmania (L.) chagasi. This is the
      first report of the disease in felines of the city of Andradina, SP, an area
      considered endemic for canine and human visceral leishmaniasis.

PMID- 21184706
TI  - Serosurvey of antibodies against spotted fever group Rickettsia spp. in horse
      farms in Northern Parana, Brazil.
AB  - Brazilian spotted fever (BSF) is an emerging disease most likely caused by
      Rickettsia rickettsii. The objective of the present study was to estimate the
      seroprevalence of BSF rickettsia infections in equines from six horse farms
      located in Londrina County, Parana, Southern Brazil. Six owners of horse farms
      situated in Cambe, Santa Fe, Guaraci and Londrina municipalities participated in
      the study. All farms were located in areas where BSF has not been reported. A
      total of 273 horses were sampled and their sera were tested by indirect
      immunofluorescence assay (IFA) using R. rickettsii and R. parkeri antigens.
      Titers equal to and greater than 64 were considered positive. Of 273 sera tested,
      15 (5.5%) reacted to R. rickettsii and 5 (1.8%) to R. parkeri. Five out of the
      six farms studied revealed seropositive animals and seropositivity rate ranged
      from 0 to 13%. The titers ranged from 64 to 512, and four samples had a titer of
      512. Nine animals reacted to R. rickettsii with titers four-fold higher than
      those for R. parkeri. These results suggest that horses in Northern Parana may
      have been exposed to rickettsiae identical or closely related to R. rickettsii.

PMID- 21184707
TI  - A first record of Amblyomma dissimile (Acari: Ixodidae) parasitizing the lizard
      Ameiva ameiva (Teiidae) in Brazil.
AB  - A non-engorged adult female Amblyomma dissimile and two Amblyomma sp. larvae were
      found parasitizing the lizard Ameiva ameiva in the municipality of Chapadinha,
      State of Maranhao. This is the first record in the state of Maranhao and fills a
      gap in the distribution of A. dissimile in Brazil. The lizard A. ameiva
      represents a new host for A. dissimile, and also the first record of this tick
      species infesting lizards of the family Teiidae in Brazil.

PMID- 21184708
TI  - First report of coenurosis in sheep in the State of Mato Grosso do Sul, Brazil.
AB  - This paper reports the first case of coenurosis in the State of Mato Grosso do
      Sul, Brazil. This disease is caused by the larval stage of the tapeworm Taenia
      multiceps (Leske, 1780). The animal in which the disease was diagnosed was an 18
      month-old ewe from an endemic area of Southern Brazil as an imported animal among
      a group of 30 sheep. The clinic-pathological condition was that commonly found in
      herbivores affected by the disease, especially sheep. Apathy, nystagmus,
      intermittent blindness, circling and pressing head against obstacles were the
      neurological signs reported. The necropsy showed that a brain lesion in the
      subcortex of the right hemisphere was a bladder-like cyst measuring 4 cm in
      diameter filled with a translucent fluid with a large number of white spherules
      (protoscolices) floating. In addition to the identification of the Coenurus
      cerebralis protoscolices, the brain tissue lesion was histopathologically
      described.

PMID- 21184709
TI  - Toxoplasma gondii antibodies on domiciled cats from Lages municipality, Santa
      Catarina State, Brazil.
AB  - Sera were collected from 300 domiciled cats from the municipality of Lages,
      Southern Brazil, to determine the prevalence of Toxoplasma gondii antibodies and
      risk factors associated. Tests for T. gondii antibodies were performed using
      indirect immunofluorescent antibody test (IFAT). Positive reactions with titers
      >=1:64 were found in 43 (14.33%) cats. A significant number of seropositive cats
      were >=6 month old (p = 0.03758) and had access to the streets or/and rural areas
      (p = 0.04185). The results indicate that T. gondii is widespread in cats in Lages
      with a prevalence of 14.33%.

PMID- 21184710
TI  - Evaluation of anthelmintic activity of liquid waste of Agave sisalana (sisal) in
      goats.
AB  - It was evaluated the anthelmintic activity of Agave sisalana (sisal) juice
      against gastrointestinal nematodes and its potential toxic effects in goats. In
      vitro tests showed more than 95% reduction in larval counts of the genus
      Haemonchus spp. at concentrations between 86.5 and 146.3 mg.mL(-1). In vivo the
      percent reduction of larvae of the fourth (L4) and fifth (L5) stages of
      Haemonchus, Oesophagostomum and Trichostrongylus was less than 95% in groups GI
      and GII, and between 80 and 90% in group GIII. A. sisalana juice at the
      concentrations tested in vitro was effective against gastrointestinal nematodes
      in goats; however, its anthelmintic efficacy was reduced when administered to
      animals.

PMID- 21184711
TI  - [The quality of the medical journals and the evaluation of the scientific
      productivity].
AB  - The knowledge when is disseminated, used and transferred to professionals
      established a relation between investigators, publishers and educators which has
      as a target the readers. A social responsibility of scientists is to look for
      solutions to problems that affect the society, since the medicine is to look for
      solutions that lead to increase the health level and to diminish the consequences
      of the disease. The evaluation of the scientific productivity, the quality of the
      journals and the education is a necessity as a part of a general evaluation of
      results. It is realize by the own institutions or by different groups. In this
      area, there is again a link between investigators-publishers-educators but with
      the readers. The aim is to communicate reflections about the quality of medical
      journals and the scientific productivity.

PMID- 21184712
TI  - [Incidence and clinical factors related with nosocomial infection in children
      with heart surgery].
AB  - BACKGROUND: The risk of nosocomial infection in pediatric patients undergoing
      heart surgery is high and proportional to the days of stay, mainly in intensive
      care units. Our objective was to determine the incidence and associated factors
      to nosocomial infections after a heart surgery. METHODS: Descriptive,
      retrospective clinical study with 64 pediatric patients underwent to a heart
      surgery. The chi(2) with Yates fix for nonparametric data test, relative risk, as
      well as incidence rate were performed. RESULTS: Nosocomial infection prevalence
      rate was 52; a fatality in infected 21.2, rate not infected of 16.1; the type of
      nosocomial infection with the highest rate of 65.6 was pneumonia, and the
      microorganism most common (rate 12.5) was the Candida. The largest number of
      infection events were 24 with a 37.5 rate. The most significant variables for
      infection were heart surgery, parenteral nutrition, nasogastric intubation and
      tracheotomy. CONCLUSIONS: The pediatric patients underwent to a heart surgery
      presented nosocomial infection in the half of the cases and the fatality rate was
      higher than the rate reported in literature.

PMID- 21184713
TI  - Changes on craniofacial structures in children with growth-hormone-deficiency.
AB  - OBJECTIVE: To describe the growth of craniofacial structures in growth-hormone
      deficiency (GHD) children during growth-hormone therapy (GHT). METHODS: A cross
      sectional sample of 46 subjects (n = 14 girls, 32 boys) aged 4-18 years was
      obtained. They were categorized into two paired groups: the reference group, for
      comparing the cephalograms, consisted in 23 healthy subjects, and the study group
      (23 patients) with GHD under GHT. Differences between groups were assessed by
      independent t-tests. RESULTS: The boys showed smaller measurements for all facial
      structures presenting significant differences in total mandibular length (Co-Pg p
      < 0.03), lower anterior facial height (ANS-Me p < 0.03) and total anterior facial
      height (N-Me p < 0.02) as well as retrognathic facial type. In girls the
      posterior cranial base length was shortened (S-Ba 29.14 +/- 3.02 mm) and show a
      high mandibular plane angle (40 +/- 5.50 degrees ) a wide relation anterior
      maxillo-mandibular (5.86 +/- 1.57 degrees ) with a statistical difference (p <
      0.05 and p < 0.04) compared with the reference group. CONCLUSIONS: We suggest
      considering the cephalometric morphology at the beginning of GHT.

PMID- 21184714
TI  - [The effect of milk products consumption in mothers during breastfeeding].
AB  - BACKGROUND: Several studies indicate that milk products consumption by mothers
      during the nursing period induce colic in the newborns. However, when mothers
      interrupt milk consumption, the colic of the newborns disappears. OBJECTIVE: to
      analyze milk composition in Mexican women according to maternal milk products
      consumption. METHODS: Seven women were studied in puerperal period, three of them
      consumed milky products and four not. All were healthy; they gave a five cc milk
      sample, which was frozen until the moment of the analysis. A double dimension
      electrophoresis in polyacrilamide gels was carried out. The protein levels were
      determined by Lowry's method. Total lipid extraction and cromatography in thin
      plaque was carried out. Total carbohydrate content was quantified. RESULTS: No
      differences were found in protein electrophoresis neither in the chromatographic
      lipid analysis. Carbohydrate content was similar in both groups. CONCLUSIONS:
      Colic in newborn depends on the idiosyncrasy of each one, and not in the supposed
      induced modifications of milk products on maternal milk consumption.

PMID- 21184715
TI  - [Rapid immune response against hepatitis B using an accelerated intradermal
      vaccination schedule].
AB  - OBJECTIVE: To analyze the prescription of antiviral and antibiotic agents in
      children with upper airway infection (UAI) during Influenza H1N1 epidemic.
      METHODS: A cross-section study (01/04/2009 to 31/03/2010) was performed. We
      analyzed the antiviral and antibiotic agents' prescription and its relation with
      the presence of the triad of symptom of suspicion (migraine, fever and cough) and
      the cost for attention (medicines and screening test). RESULTS: 838 children were
      attendance for UAI, 40.3% with the suspicion triad. In 733 patients, the
      screening test were done with 155 positive results (120 had the triad). All
      patient with a positive result received oseltamivir. During the first five months
      of the epidemic, the medical prescriptions were: antibiotics 60-85%, 0-7% anti
      viral and 20-30% symptomatic drugs. At the 6th at 8th months (peak of outbreak)
      antibiotics 35-70%, anti-virals 20-25% and 10-30% symptomatic drugs. At final
      months (9th to 11th) antimicrobials 65-80%, anti-virals 20-30% and symptomatic 0
      10%. The cost for URI attention increased a 27%. CONCLUSIONS: Medical
      prescription changed during the epidemic, with an increased in the anti-virals,
      especially for patients with high suspicion for influenza and positive screening
      test.

PMID- 21184716
TI  - [Therapeutic conduct in children attended in emergency room during the epidemic
      of influenza A H1N1].
AB  - OBJECTIVE: To analyze the prescription of antiviral and antibiotic agents in
      children with upper airway infection (UAI) during Influenza H1N1 epidemic.
      METHODS: A cross-section study (01/04/2009 to 31/03/2010) was performed. We
      analyzed the antiviral and antibiotic agents' prescription and its relation with
      the presence of the triad of symptom of suspicion (migraine, fever and cough) and
      the cost for attention (medicines and screening test). RESULTS: 838 children were
      attendance for UAI, 40.3% with the suspicion triad. In 733 patients, the
      screening test were done with 155 positive results (120 had the triad). All
      patient with a positive result received oseltamivir. During the first five months
      of the epidemic, the medical prescriptions were: antibiotics 60-85%, 0-7% anti
      viral and 20-30% symptomatic drugs. At the 6th at 8th months (peak of outbreak)
      antibiotics 35-70%, antivirals 20-25% and 10-30% symptomatic drugs. At final
      months (9th to 11th) antimicrobials 65-80%, antivirals 20-30% and symptomatic 0
      10%. The cost for URI attention increased a 27%. CONCLUSIONS: Medical
      prescription changed during the epidemic, with an increased in the antivirals,
      especially for patients with high suspicion for influenza and positive screening
      test.

PMID- 21184717
TI  - [The practice of medicine in 1910].
AB  - The aim is to describe the environmental and the practice of the medicine around
      the 1910, year of the Mexican Revolution. Prominent physicians and theirs
      contributions are describe. All of them from the Mexican clinical school
      development by Manuel Carpio and Miguel Jimenez. It is stand out the progress of
      the Mexican medicine with the incorporation of the European advances into the
      daily practice. It is also describe the development and contemporary practice of
      surgery of the Mexican surgery school forced by surgeons like Miguel Munoz,
      Francisco Montes de Oca and Rafael Lavista.

PMID- 21184718
TI  - [Acinetobacter baumannii bacteremia].
AB  - Acinetobacter baumannii has emerged as an important nosocomial pathogen. It is
      difficult to control and treat. The most seriously ill patients and those
      previously infected are more likely than others to be infected or colonized by A.
      baumannii. The epidemiology of A. baumannii infection is complex, with the
      coexistence of epidemic and endemic infections. The A. baumannii are the species
      isolated in 90% of the nosocomial infections and in 92% of the nosocomial
      bacteremias. The intensive care units presented the greater number of nosocomial
      bacteremias by A. baumannii. The most common sources of A. baumannii are
      respiratory tract, surgical wound, catheter, urinary tract and others. The most
      frequently clinical manifestation is sepsis and a fulminating course is observed
      when the patient presents septic shock. Progressive resistance of A. baumannii to
      antimicrobial limits the therapeutic options. The patients with A. baumannii
      multidrug-resistant present an excessive rate of attributed mortality, length of
      stay and costs.

PMID- 21184719
TI  - [Prenatal dexametasone and periventricular leucomalacia in prematures].
AB  - BACKGROUND: Prematurity is observed in 5-8% of deliveries, and is frequent cause
      of handicap. Premature have 5-24% risk for developing periventricular
      leukomalacia (PLM). The use of antenatal steroids (AS) is controversial for
      preventing PLM. METHODS: We studied 110 premature neonates < 1500 g, divided in 2
      groups: control (group 1, n = 55), and group 2 (n = 55) who received antenatal
      dexamethasone. We registered clinical data, evolution and use of oxygen or
      mechanical ventilation. At one month age a transfontanelar ultrasound was done
      looking specific PLM. RESULTS: In group 1, found 6/55 (10.9%) with PLM and 3/55
      (5.4%) in group 2, RR = 0.5, CI 95% (0.13-1.90). In group 1: 30/55 (54.54%) the
      ultrasound was normal; in 16 (29%) had intraventricular haemorrhage, and in 3
      cases (5.45%) had severe hydrocephalus. In group 2: 32/55 (58.18%) ultrasound was
      normal, 16/55 (29%) had intraventricular haemorrhage, 4/55 (7.27%) had severe
      hydrocephalus. We did not find significant difference between other variables in
      both groups. CONCLUSIONS: There was no significant difference in PLM incidence
      between patients who did or did not received antenatal dexamethasone.

PMID- 21184720
TI  - [Nutritional indicators in children with acute lymphoblastic leukemia].
AB  - BACKGROUND: A nutritional assessment allows to determine the state of nutrition
      and to predict the possibility of displaying additional risks for a disease.
      Previous investigations have verified that it is not sufficient for children with
      acute lymphoblastic leukemia (ALL) to have registry of anthropometric
      measurements such as age, weight, and height. Given the previous information, it
      is necessary to conduct studies with nutritional indicators that contribute to
      understanding their importance in children with ALL. OBJECTIVE: To compare the
      nutritional values of five indicators of children with and without ALL. METHODS:
      A sample of 21 children with a diagnosis of ALL and 54 children without ALL
      (control) participated in the study; the children's ages ranged between 1.3 to 10
      years. Comparisons between cases and controls were performed. RESULTS: Indicators
      of albumin and triceps skin fold showed differences between the groups (p <
      0.005). CONCLUSIONS: Children with ALL at time of diagnosis had nutritional
      deficiencies of subcutaneous fat reserve and protein. These indicators could be
      part of the prognostic and standard of care for children with this cancer.

PMID- 21184721
TI  - [Prevalence of risk factors for drowning at home related to the socioeconomic
      level].
AB  - OBJECTIVE: To measure the association between social economic conditions and the
      presence of risk factors for drowning at home in children under 5 years old
      within metropolitan area of Guadalajara. METHODS: Surveyed 439 family houses were
      lived children less than 5 years old randomly selected during 18 months.
      Variables included social economic level, demographics, and bodies of water and
      accessories present at the house. RESULTS: Children in the lower social economic
      level are exposed more frequently to buckets and laundry tubs in the house than
      children of medium level families, but not to underground cisterns and wells. No
      mater the equal number of underground cisterns and wells, safety accessories and
      equipment are less frequent in low socioeconomic families. Children in the low
      social economic level spend more time at their homes than medium socioeconomic
      level children. CONCLUSIONS: It seems that the high frequency of drowning among
      low social economic families is related to a higher exposure to risk factors. It
      is necessary to improve mechanisms and change environmental conditions to reduce
      the number of children drowning at home.

PMID- 21184722
TI  - [Experience in the management of pediatric patients with Gaucher disease].
AB  - Among lysosomal storage diseases, Gaucher disease depicts the highest rate of
      incidence, according with the international epidemiological reports. Gaucher
      disease is due to an impairing of the acid beta-glucosidase enzyme, since its
      lack promotes accumulation of the sphingolipid glucosylceramide at macrophages,
      leading to heterogeneous multiorganic damage (visceral, skeletal, and central
      nervous system affectation). This paper portrays a series of clinical cases of
      Gaucher disease with patients treated at the same city (Monterrey, Nuevo Leon),
      at the Paediatric Haematology Department of the Specialties General Hospital,
      UMAE 25, in Monterrey of the Instituto Mexicano del Seguro Social. Gaucher
      disease is symptomatic since early childhood in a good proportion of patients.
      The patients in this serie was treated with enzyme replacement therapy, and share
      the typical overall features of the disease.

PMID- 21184723
TI  - [Holt-Oram syndrome associated with facial anomalies. A case report].
AB  - Cardiomyelic syndromes have skeletal malformations of the upper limb and
      congenital heart disease, and are related to mutations in transcription factors
      with T-Box domains. Holt-Oram syndrome is characterized by upper-extremity
      malformations involving the radial, thenar, or carpal bones and congenital heart
      defects. It is inherited in an autosomal dominant manner, a mutation in TBX5 gene
      located on chromosome 12 (12q24.1) is associated with variable phenotypes. This
      is an unusual case of a patient with Holt-Oram syndrome associated with facial
      anomalies: hemifacial microsomia on the right side, forehead prominent and tall,
      hypertelorism, depressed nasal bridge, low set ears and micrognathia. The
      presentation broadens the clinical spectrum with delineation of facial dysmorphic
      features.

PMID- 21184724
TI  - [The clinical guidelines of practice project at the Instituto Mexicano del Seguro
      Social].
AB  - The advance in the knowledge and technology is growing quickly and greater
      quantity, so it is difficult for the health professional to access to whole
      information that is generated every day on diagnostic and therapeutic strategies
      more effective, so the clinic practice guidelines (CPG) is a resource to support
      the updating of the health professional and support them in making clinical
      decisions. The CPG is also a better support to the manager of health services in
      making decisions regarding the strategies that have performed for the patient and
      less risk to the individual and collective health. They also support the response
      capacity of the medical units and hospitals and guide the planning of services to
      the optimization of the resources. This paper summarizes the methodology of a
      national project for the development of GPC coordinated by the Mexican Social
      Security Institute with the collaboration of more than 1200 health professionals
      of the institution in a great effort institutional update and make information
      accessible to the entire health sector, which also defines the steps to upgrade
      and maintain the updating of knowledge and technology expressed in them.

PMID- 21184725
TI  - [A clinical guideline for diagnosis and treating of diabetes during pregnancy].
AB  - BACKGROUND: Metabolic disturbance commonly occurs during pregnancy and perinatal
      outcome harms, with increased maternal-fetal morbidity. The prevalence of
      diabetes during pregnancy in Mexico is 7%. OBJECTIVE: To develop a guideline
      available to the staff of the first, second and third level of care, that
      includes recommendations based on the best available evidence. METHODS: Clinical
      questions were formulated and structured. Standardized sequence was established
      to search for practice guidelines from the clinical questions raised on diagnosis
      and treatment of diabetes and pregnancy. The working group selected clinical
      practice guidelines. We found eleven guidelines which took many of the
      recommendations. For recommendations not included in the reference guides the
      search process was conducted in PubMed and Cochrane Library. The results were
      expressed as levels of evidence and grade of recommendation. CONCLUSIONS:
      Diabetes mellitus during pregnancy increases perinatal morbidity and mortality.
      The recommendations in this evidence-based guide will help to make diagnosis and
      treatment standardized to reduce the consequences of disease.

PMID- 21184728
TI  - Quantification of protein concentration by the Bradford method in the presence of
      pharmaceutical polymers.
AB  - We investigated how the Bradford assay for measurements of protein released from
      a drug formulation may be affected by a concomitant release of a pharmaceutical
      polymer used to formulate the protein delivery device. The main result is that
      polymer-caused perturbations of the Coomassie dye absorbance at the Bradford
      monitoring wavelength (595nm) can be identified and corrected by recording
      absorption spectra in the region of 350-850mm. The pharmaceutical polymers
      Carbopol and chitosan illustrate two potential types of perturbations in the
      Bradford assay, whereas the third polymer, hydroxypropylmethylcellulose (HPMC),
      acts as a nonperturbing control. Carbopol increases the apparent absorbance at
      595nm because the polymer aggregates at the low pH of the Bradford protocol,
      causing a turbidity contribution that can be corrected quantitatively at 595nm by
      measuring the sample absorbance at 850nm outside the dye absorption band.
      Chitosan is a cationic polymer under Bradford conditions and interacts directly
      with the anionic Coomassie dye and perturbs its absorption spectrum, including
      595nm. In this case, the Bradford method remains useful if the polymer
      concentration is known but should be used with caution in release studies where
      the polymer concentration may vary and needs to be measured independently.

PMID- 21184729
TI  - Magnetic beads-assisted mild enrichment procedure for weak-binding lectins.
AB  - Investigating unidentified weak-acting lectins is important for understanding
      glycan-related phenomena. We have developed an improved screening method for weak
      acting lectins using glycan-conjugated magnetic beads (or glycobeads) involving a
      partial washing method and named it the mild enrichment procedure. Weak-acting
      lectins exist in equilibrium between bound lectin and free lectin produced by
      dissociation, whereas most tight-binding lectin exists in a bound state. The
      conventional washing step, in which the solution phase is replaced, may remove
      dissociated lectin from around the glycobeads; therefore, we attempted to leave a
      buffer space around the glycobeads to maintain the association-dissociation
      equilibrium of weak-acting lectins. Our results revealed that our mild enrichment
      procedure for screening for weak interactions, such as maltose-concanavalin A
      (K(a)~10(4)M(-1)) and lactose-peanut agglutinin (K(a)~10(3)M(-1)) interactions,
      was more effective than conventional batch methods.

PMID- 21184730
TI  - A gold nanoparticle-mediated enzyme bioreactor for inhibitor screening by
      capillary electrophoresis.
AB  - A facile protocol to prepare highly effective and durable in-line enzyme
      bioreactors inside capillary electrophoresis (CE) columns was developed. To
      demonstrate the methodology, l-glutamic dehydrogenase (GLDH) was selected as the
      model enzyme. GLDH was first immobilized onto 38-nm-diameter gold nanoparticles
      (GNPs), and the functionalized GNPs were then assembled on the inner wall at the
      inlet end of the CE capillary treated with polyethyleneimine (PEI), producing an
      in-line GLDH bioreactor. Compared with a GLDH bioreactor prepared by immobilizing
      GLDH directly on PEI-treated capillary, the GNP-mediated bioreactor showed a
      higher enzymatic activity and a much better stability. The in-capillary enzyme
      bioreactor was proven to be very useful for screening of GLDH inhibitors
      deploying the GLDH-catalyzed alpha-ketoglutaric acid reaction. The screening
      assay was preliminarily validated by using a known GLDH inhibitor, namely
      perphenazine. A Z' factor value of 0.95 (n=10) was obtained, indicating that the
      screening results were highly reliable. Screening of GLDH inhibitors present in
      medicinal plant extracts by the proposed method was demonstrated. The inhibition
      percentages were found to be 53% for Radix scutellariae, 45% for Radix
      codonopsis, 37% for Radix paeoniae alba, and 0% for the other 22 extracts tested
      at a concentration of 0.6mg extract/ml.

PMID- 21184731
TI  - TOX4 and its binding partners recognize DNA adducts generated by platinum
      anticancer drugs.
AB  - Platinating agents are commonly prescribed anticancer drugs damaging DNA. Induced
      lesions are recognized by a wide range of proteins. These are involved in
      cellular mechanisms such as DNA repair, mediation of cytotoxicity or chromatin
      remodeling. They therefore constitute crucial actors to understand pharmacology
      of these drugs. To expand our knowledge about this subproteome, we developed a
      ligand fishing trap coupled to high throughput proteomic tools. This trap is made
      of damaged plasmids attached to magnetic beads, and was exposed to cell nuclear
      extracts. Retained proteins were identified by nanoHPLC coupled to tandem mass
      spectrometry. This approach allowed us to establish a list of 38 proteins
      interacting with DNA adducts generated by cisplatin, oxaliplatin and satraplatin.
      Some of them were already known interactome members like high mobility group
      protein 1 (HMGB1) or the human upstream binding factor (hUBF), but we also
      succeeded in identifying unexpected proteins such as TOX HMG box family member 4
      (TOX4), phosphatase 1 nuclear targeting subunit (PNUTS), and WD repeat-containing
      protein 82 (WDR82), members of a recently discovered complex. Interaction between
      TOX4 and platinated DNA was subsequently validated by surface plasmon resonance
      imaging (SPRi). These interactions highlight new cellular responses to DNA damage
      induced by chemotherapeutic agents.

PMID- 21184732
TI  - WNT signaling controls expression of pro-apoptotic BOK and BAX in intestinal
      cancer.
AB  - In a majority of cases, colorectal cancer is initiated by aberrant activation of
      the WNT signaling pathway. Mutation of the genes encoding the WNT signaling
      components adenomatous polyposis coli or beta-catenin causes constitutively
      active beta-catenin/TCF-mediated transcription, driving the transformation of
      intestinal crypts to cancer precursor lesions, called dysplastic aberrant crypt
      foci. Deregulated apoptosis is a hallmark of adenomatous colon tissue. However,
      the contribution of WNT signaling to this process is not fully understood. We
      addressed this role by analyzing the rate of epithelial apoptosis in aberrant
      crypts and adenomas of the Apc(Min/+) mouse model. In comparison with normal
      crypts and adenomas, aberrant crypts displayed a dramatically increased rate of
      apoptotic cell death. Expression profiling of apoptosis-related genes along the
      crypt-villus axis and in Apc mutant adenomas revealed increased expression of two
      pro-apoptotic Bcl-2 family members in intestinal adenomas, Bok and Bax. Analysis
      of the colon of familial adenomatous polyposis (FAP) patients along the crypt-to
      surface axis, and of dysplastic crypts, corroborated this expression pattern.
      Disruption of beta-catenin/TCF-4-mediated signaling in the colorectal cancer cell
      line Ls174T significantly decreased BOK and BAX expression, confirming WNT
      dependent regulation in intestinal epithelial cells. Our results suggest a
      feedback mechanism by which uncontrolled epithelial cell proliferation in the
      stem cell compartment can be counterbalanced by an increased propensity to
      undergo cell death.

PMID- 21184733
TI  - IL-13 suppresses double-stranded RNA-induced IFN-lambda production in lung cells.
AB  - Acute asthma exacerbations are frequently associated with respiratory viral
      infections. Although impaired production of type III IFNs (IFN-lambdas) is
      related to the severity of asthma exacerbation, the mechanisms underlying
      deficient IFN-lambda production in asthma are poorly understood. Airway
      epithelial cells were stimulated in vitro with a synthetic mimetic of viral
      double-stranded RNA (dsRNA). IL-13, a crucial cytokine responsible for asthma
      pathogenesis, suppressed dsRNA-induced expression of IFN-lambdas, and JAK
      inhibitor AG490 prevented the suppression by IL-13. IL-13 per se did not affect
      IFN-lambda production or the expressions of membrane dsRNA receptor TLR3 and of
      cytoplasmic receptors RIG-I and MDA5. IL-13-deficient mice exhibited more
      enhanced IFN-lambda expression after intratracheal instillation of dsRNA than
      wild-type mice, whereas IFN-lambda expression after dsRNA was absent in the mouse
      lungs of the OVA-induced asthma model. These findings suggest that IL-13 may be a
      putative cytokine suppressing IFN-lambda production against airway viral
      infections in asthmatics.

PMID- 21184734
TI  - Dopamine D2 and D4 receptor heteromerization and its allosteric receptor-receptor
      interactions.
AB  - Dopamine D(2) and D(4) receptors partially codistribute in the dorsal striatum
      and appear to play a fundamental role in complex behaviors and motor function.
      The discovery of D(2)R-D(4.)(x)R (D(4.2)R, D(4.4)R or D(4.7)R) heteromers has
      been made in cellular models using co-immunoprecipitation, in situ Proximity
      Ligation Assays and BRET(1) techniques with the D(2)R and D(4.7)R receptors being
      the least effective in forming heteromers. Allosteric receptor-receptor
      interactions in D(2)R-D(4.2)R and D(2)R-D(4.4) R heteromers were observed using
      the MAPK assays indicating the existence of an enhancing allosteric receptor
      receptor interaction in the corresponding heteromers between the two orthosteric
      binding sites. The bioinformatic predictions suggest the existence of a basic set
      of common triplets (ALQ and LRA) in the two participating receptors that may
      contribute to the receptor-receptor interaction interfaces.

PMID- 21184735
TI  - Involvement of HDAC1 in E-cadherin expression in prostate cancer cells; its
      implication for cell motility and invasion.
AB  - In this study, we investigate the molecular mechanism by which histone
      deacetylase (HDAC) inhibitors exert anti-invasiveness effect against prostate
      cancer cells. We first evaluate the growth inhibition effect of HDAC inhibitors
      in prostate cancer cells, which is accompanied by induction of p21(WAF1)
      expression and accumulation of acetylated histones. And we found that the
      migration and invasion of prostate cancer cells is strongly inhibited by
      treatment with HDAC inhibitors. In parallel, E-cadherin level is highly up
      regulated in HDAC inhibitor-treated prostate cancer cells. And siRNA knockdown of
      E-cadherin significantly diminishes the anti-invasion effect of HDAC inhibitors,
      indicating that E-cadherin overexpression is one of possible mechanism for anti
      invasion effect of HDAC inhibitors. Furthermore, specific downregulation of
      HDAC1, but not HDAC2, causes E-cadherin expression and subsequent inhibition of
      cell motility and invasion. Collectively, our data demonstrate that HDAC1 is a
      major repressive enzyme for E-cadherin expression as well as HDAC inhibitor
      mediated anti-invasiveness.

PMID- 21184736
TI  - Identification of the methylation preference region in heterogeneous nuclear
      ribonucleoprotein K by protein arginine methyltransferase 1 and its implication
      in regulating nuclear/cytoplasmic distribution.
AB  - Protein arginine methylation plays crucial roles in numerous cellular processes.
      Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a multi-functional protein
      participating in a variety of cellular functions including transcription and RNA
      processing. HnRNP K is methylated at multiple sites in the glycine- and arginine
      rich (RGG) motif. Using various RGG domain deletion mutants of hnRNP K as
      substrates, here we show by direct methylation assay that protein arginine
      methyltransferase 1 (PRMT1) methylated preferentially in a.a. 280-307 of the RGG
      motif. Kinetic analysis revealed that deletion of a.a. 280-307, but not a.a. 308
      327, significantly inhibited rate of methylation. Importantly, nuclear
      localization of hnRNP K was significantly impaired in mutant hnRNP K lacking the
      PRMT1 methylation region or upon pharmacological inhibition of methylation.
      Together our results identify preferred PRMT1 methylation sequences of hnRNP K by
      direct methylation assay and implicate a role of arginine methylation in
      regulating intracellular distribution of hnRNP K.

PMID- 21184737
TI  - Ectopic expression of H2AX protein promotes TrkA-induced cell death via
      modulation of TrkA tyrosine-490 phosphorylation and JNK activity upon DNA damage.
AB  - We previously reported that TrkA overexpression causes accumulation of gammaH2AX
      proteins in the cytoplasm, subsequently leading to massive cell death in U2OS
      cells. To further investigate how cytoplasmic H2AX is associated with TrkA
      induced cell death, we established TrkA-inducible cells stably expressing GFP
      tagged H2AX. We found that TrkA co-localizes with ectopically expressed GFP-H2AX
      proteins in the cytoplasm, especially at the juxta-nuclear membranes, which
      supports our previous results about a functional connection between TrkA and
      gammaH2AX in TrkA-induced cell death. gammaH2AX production from GFP-H2AX proteins
      was significantly increased when TrkA was overexpressed. Moreover, ectopic
      expression of H2AX activated TrkA-mediated signal pathways via up-regulation of
      TrkA tyrosine-490 phosphorylation. In addition, suppression of TrkA tyrosine-490
      phosphorylation under a certain condition was removed by ectopic expression of
      H2AX, indicating a functional role of H2AX in the maintenance of TrkA activity.
      Indeed, TrkA-induced cell death was highly elevated by ectopic H2AX expression,
      and it was further accelerated by DNA damage via JNK activation. These all
      results suggest that cytoplasmic H2AX could play an important role in TrkA
      mediated cell death by modulating TrkA upon DNA damage.

PMID- 21184738
TI  - Specific inhibition of nitric oxide synthases at different time points in a
      murine model of pulmonary sepsis.
AB  - Excessive production of nitric oxide (NO) by NO synthase (NOS) and a subsequent
      oxidative stress reaction are thought to be critically involved in the
      pathophysiology of sepsis. Previous studies suggested that NO production by
      neuronal NOS (nNOS) and inducible NOS (iNOS) is implemented in the disease
      process at different time points after the injury. Here we tested the roles of
      selective pharmacological inhibition of nNOS and iNOS at different time points in
      a murine model of pulmonary sepsis. The injury was induced by intranasal
      administration of live Pseudomonas aeruginosa (3.2*10(7) colony-forming units) in
      C57BL/6 wild-type mice. The animals received no treatment (control) or treatment
      with a specific nNOS inhibitor (4 or 8h), iNOS inhibitor (4 or 8h), or non
      specific NOS inhibitor (4 or 8h). In controls, the injury was associated with
      excessive releases of pro-inflammatory cytokines in the plasma, enhanced tissue
      lipid peroxidation, and decreased survival. Non-specific NOS inhibition at either
      time point did not influence survival and was not further investigated. While
      nNOS inhibition at 4h was associated with a trend toward improved survival and
      significantly reduced contents of lung nitrite/nitrate (NO(x)) and liver
      malondialdehyde, the blockade of nNOS at 8h had no effect on these parameters. In
      contrast, early iNOS inhibition was associated with a trend toward decreased
      survival and no effects on lung NO(x) and liver malondialdehyde contents, whereas
      later iNOS blockade was associated with decreased malondialdehyde content in
      liver homogenates. In conclusion, pulmonary sepsis in mice may be beneficially
      influenced by specific pharmacological nNOS inhibition at an earlier time point
      and iNOS inhibition at a later time points post-injury. Future investigations
      should identify the time changes of the expression and activation of NOS
      isoforms.

PMID- 21184739
TI  - Characterization and biological actions of N-terminal truncated forms of glucose
      dependent insulinotropic polypeptide.
AB  - The N-terminal domain of glucose-dependent insulinotropic polypeptide (GIP) plays
      an important role in regulating biological activity. This study examined
      biological properties of several N-terminal truncated forms of GIP and two novel
      forms with substitutions at Phe position-6 with Arg or Val. GIP(6-42), GIP(R6
      42), GIP(V6-42), GIP(7-42) and GIP(9-42) stimulated cAMP production in BRIN-BD11
      cells similar to native GIP, whereas responses to GIP(3-42), GIP(4-42), GIP(5-42)
      and GIP(8-42) were reduced (P<0.01 to P<0.001). GIP-induced cyclic AMP production
      was significantly inhibited by GIP(3-42), GIP(4-42), GIP(5-42), GIP(6-42), GIP(R6
      42), GIP(7-42) and GIP(8-42) (P<0.001). Compared with native GIP, in vitro
      insulinotropic activity of GIP(3-42), GIP(4-42), GIP(5-42), GIP(7-42) and GIP(8
      42) was reduced (P<0.05 to P<0.001), with GIP(4-42), GIP(5-42), GIP(7-42) and
      GIP(8-42) also potently inhibiting GIP-stimulated insulin secretion (P<0.001). In
      ob/ob mice, GIP(4-42) and GIP(8-42) increased (P<0.05 to P<0.01) plasma glucose
      concentrations compared to the glucose-lowering action of native GIP. When GIP(8
      42) was co-administered with native GIP it countered the ability of the native
      peptide to lower plasma glucose and increase circulating insulin concentrations.
      These data confirm the importance of the N-terminal region of GIP in regulating
      bioactivity and reveal that sequential truncation of the peptide yields novel GIP
      receptor antagonists which may have functional significance.

PMID- 21184740
TI  - Gln3-Gcn4 hybrid transcriptional activator determines catabolic and biosynthetic
      gene expression in the yeast Saccharomyces cerevisiae.
AB  - The yeast Saccharomyces cerevisiae is able to sense the availability and quality
      of nitrogen sources and the intrinsic variation of amino acid disponibility for
      protein synthesis. When this yeast is provided with secondary nitrogen sources,
      transcription of genes encoding enzymes involved in their catabolism is elicited
      through the action of Gln3, which constitutes the main activator of the Nitrogen
      Catabolite Repression network (NCR). Activation of genes encoding enzymes
      involved in the amino acid biosynthetic pathways is achieved through the action
      of the GCN4-encoded transcriptional modulator whose transcriptional activation is
      induced at the translational level by limitation for any amino acid. Thus the
      role of each one of these activators had been secluded to either catabolic or
      biosynthetic pathways. However, some observations have suggested that under
      peculiar physiological conditions, Gln3 and Gcn4 could act simultaneously in
      order to contemporaneously increase expression of both sets of genes. This paper
      addresses the question of whether Gln3 and Gcn4 cooperatively determine
      expression of their target genes. Results presented herein show that induced
      expression of catabolic and biosynthetic genes when cells are grown under
      nitrogen derepressive conditions and amino acid deprivation is dependent on the
      concurrent action of Gln3 and Gcn4, which form part of a unique transcriptional
      complex. We propose that the combination of Gln3 and Gcn4 results in the
      constitution of a hybrid modulator which elicits a novel transcriptional
      response, not evoked when these modulators act in a non-combinatorial fashion.

PMID- 21184741
TI  - Posttranslational negative regulation of glycosylated and non-glycosylated BCRP
      expression by Derlin-1.
AB  - Human breast cancer resistance protein (BCRP)/MXR/ABCG2 is a well-recognized ABC
      half-transporter that is highly expressed at the apical membrane of many normal
      tissues and cancer cells. BCRP facilitates disposition of endogenous and
      exogenous harmful xenobiotics to protect cells/tissues from xenobiotic-induced
      toxicity. Despite the enormous impact of BCRP in the physiological and
      pathophysiological regulation of the transport of a wide variety of substrates,
      little is known about the factors that regulate posttranslational expression of
      BCRP. Here, we identified Derlin-1, a member of a family of proteins that bears
      homology to yeast Der1p, as a posttranslational regulator of BCRP expression.
      Overexpression of Derlin-1 suppressed ER to Golgi transport of wild-type (WT)
      BCRP that is known to be efficiently trafficked to the plasma membrane. On the
      other hand, protein expression of N596Q variant of BCRP, N-linked glycosylation
      deficient mutant that preferentially undergoes ubiquitin-mediated ER-associated
      degradation (ERAD), was strongly suppressed by the overexpression of Derlin-1,
      whereas knockdown of Derlin-1 stabilized N596Q protein, suggesting a negative
      regulatory role of Derlin-1 for N596Q protein expression. Notably, knockdown of
      Derlin-1 also stabilized the expression of tunicamycin-induced deglycosylated WT
      BCRP protein, implying the importance of glycosylation state for the recognition
      of BCRP by Derlin-1. Thus, our data demonstrate that Derlin-1 is a negative
      regulator for both glycosylated and non-glycosylated BCRP expression and provide
      a novel posttranslational regulatory mechanism of BCRP by Derlin-1.

PMID- 21184742
TI  - RPAP3 enhances cytotoxicity of doxorubicin by impairing NF-kappa B pathway.
AB  - Activation of anti-apoptotic gene transcription by NF-kappaB (nuclear factor
      kappa B) has been reported to be linked with a resistance of cancer cells against
      chemotherapy. NEMO (NF-kappaB essential modulator) interacts with a number of
      proteins and modulates the activity of NF-kappaB pathway. In this study, we
      revealed that RPAP3 (RNA polymerase II-associated protein 3) possesses an
      activity to bind with NEMO and to inhibit the ubiquitination of NEMO and that
      RPAP3 enhances doxorubicin-induced cell death in breast cancer cell line T-47D
      through the marked impairment of NF-kappaB pathway. These results indicate that
      RPAP3 may be a novel modulator of NF-kappaB pathway in apoptosis induced by anti
      cancer chemotherapeutic agents.

PMID- 21184743
TI  - Nonmuscle myosin IIA is required for lamellipodia formation through binding to
      WAVE2 and phosphatidylinositol 3,4,5-triphosphate.
AB  - Investigation of the mechanism underlying cell membrane-targeted WAVE2 capture by
      phosphatidylinositol 3,4,5-triphosphate (PIP(3)) through IRSp53 revealed an
      unidentified 250-kDa protein (p250) bound to PIP(3). We identified p250 as
      nonmuscle myosin IIA heavy chain (MYH9) by mass spectrometry and immunoblot
      analysis using anti-MYH9 antibody. After stimulation with insulin-like growth
      factor I (IGF-I), MYH9 colocalized with PIP(3) in lamellipodia at the leading
      edge of cells. Depletion of MYH9 expression by small interfering RNA (siRNA) and
      inhibition of myosin II activity by blebbistatin abrogated the formation of actin
      filament (F-actin) arcs and lamellipodia induced by IGF-I. MYH9 was
      constitutively associated with WAVE2, which was dependent on myosin II activity,
      and the MYH9-WAVE2 complex colocalized to PIP(3) at the leading edge after IGF-I
      stimulation. These results indicate that MYH9 is required for lamellipodia
      formation since it provides contractile forces and tension for the F-actin
      network to form convex arcs at the leading edge through constitutive binding to
      WAVE2 and colocalization with PIP(3) in response to IGF-I.

PMID- 21184744
TI  - Sirtuins and inflammation: Friends or foes?
AB  - Lysine acetylation/deacetylation has been recognized as an important
      posttranslational modification regulating numerous cellular processes. Sirtuins
      represent novel players in these complex regulatory circuits. These NAD-dependent
      lysine-deacetylases have attracted much interest based on their role in the
      regulation of lifespan in lower organisms, and their capacity to interfere with
      cell growth, proliferation and survival in response to stress. Their absolute
      requirement for NAD suggests that these enzymes may represent an important
      molecular link between metabolism and several human disorders such as diabetes
      and cancer. More recently, the identification of several transcription factors
      known to play a role in the immune system as sirtuin substrates has suggested
      that this family of enzymes may also play an important role in the regulation of
      inflammation, a pathological situation with clear links to metabolism and aging
      in humans. We review herein the possible links between nuclear sirtuins and the
      regulation of an immune response, and discuss the possible strategies that may
      lead to the development of novel therapeutic approaches to treat inflammation by
      targeting sirtuin activity.

PMID- 21184745
TI  - In vitro liver metabolism of aclidinium bromide in preclinical animal species and
      humans: identification of the human enzymes involved in its oxidative metabolism.
AB  - The metabolism of aclidinium bromide, a novel long-acting antimuscarinic drug for
      the maintenance treatment of chronic obstructive pulmonary disorder, has been
      investigated in liver microsomes and hepatocytes of mice, rats, rabbits, dogs,
      and humans. Due to the rapid hydrolysis of this ester compound, two distinct
      radiolabeled forms of aclidinium were studied. The main biotransformation route
      of aclidinium was the hydrolytic cleavage of the ester moiety, resulting in the
      formation of the alcohol metabolite (M2, LAS34823) and carboxylic acid metabolite
      (m3, LAS34850), which mainly occurred non-enzymatically. By comparison, the
      oxidative metabolism was substantially lower and the metabolite profiles were
      similar across all five species examined. Aclidinium was metabolized oxidatively
      to four minor primary metabolites that were identified as monohydroxylated
      derivatives of aclidinium at the phenyl (M4) and glycolyl (m6 and m7) moieties of
      the molecule. The NADPH-dependent metabolite m4 involved the loss of one of the
      thiophene rings of aclidinium. Incubations with human recombinant P450 isoforms
      and inhibition studies with selective chemical inhibitors and antibodies of human
      P450 enzymes demonstrated that the oxidative metabolism of aclidinium is
      primarily mediated by CYP3A4 and CYP2D6. Additionally, up to eight secondary
      metabolites were also characterized, involving further hydrolysis, oxidation, or
      glucuronidation of the primary metabolites. Also, the liver oxidative metabolism
      of the alcohol metabolite (LAS34823) resulted in the production of one
      hydroxylated metabolite (M1) mediated by human CYP2D6, whereas the acid
      metabolite (LAS34850) was not metabolized enzymatically, although a minor non
      enzymatic and NADPH-dependent reduction was observed.

PMID- 21184746
TI  - Autophagy inhibition enhances apoptosis triggered by BO-1051, an N-mustard
      derivative, and involves the ATM signaling pathway.
AB  - In a previous study, BO-1051, an N-mustard linked with a DNA-affinic molecule,
      was shown to target various types of cancer cell lines. In the present study, we
      aimed to investigate the cytotoxicity, as well as the underlying mechanism, of BO
      1051. We found that BO-1051 simultaneously induced apoptosis and autophagy in
      hepatocellular carcinoma cell lines. DNA double strand breaks induced by BO-1051
      activated the ATM signaling pathway and subsequently resulted in caspase
      dependent apoptosis. When autophagy was inhibited in its early or late stages,
      apoptosis was significantly enhanced. This result indicated autophagy as a
      cytoprotective effect against BO-1051-induced cell death. We further inhibited
      ATM activation using an ATM kinase inhibitor or ATM-specific siRNA and found that
      while apoptosis was blocked, autophagy also diminished in response to BO-1051. We
      not only determined a signaling pathway induced by BO-1051 but also clarified the
      linkage between DNA damage-induced apoptosis and autophagy. We also showed that
      BO-1051-induced autophagy acts as a cytoprotective reaction and downstream target
      of the ATM-signaling pathway. This research revealed autophagy as a universal
      cytoprotective response against DNA damage-inducing chemotherapeutic agents,
      including BO-1051, cisplatin, and doxorubicin, in hepatocellular carcinoma cell
      lines. Autophagy contributes to the remarkable drug resistance ability of liver
      cancer.

PMID- 21184747
TI  - Strategies for the identification of allosteric modulators of G-protein-coupled
      receptors.
AB  - Once considered a pharmacological curiosity, allosteric modulation of seven
      transmembrane domain G-protein-coupled receptors (GPCRs) has emerged as a
      potentially powerful means to affect receptor function for therapeutic purposes.
      Allosteric modulators, which interact with binding sites topologically distinct
      from the orthosteric ligand binding sites, can potentially provide improved
      selectivity and safety, along with maintenance of spatial and temporal aspects of
      GPCR signaling. Accordingly, drug discovery efforts for GPCRs have increasingly
      focused on the identification of allosteric modulators. This review is devoted to
      an examination of the strategies, challenges, and opportunities for high
      throughput screening for allosteric modulators of GPCRs, with particular focus on
      the identification of positive allosteric modulators.

PMID- 21184748
TI  - Soraphen A, an inhibitor of acetyl CoA carboxylase activity, interferes with
      fatty acid elongation.
AB  - Acetyl CoA carboxylase (ACC1 and ACC2) generates malonyl CoA, a substrate for de
      novo lipogenesis (DNL) and an inhibitor of mitochondrial fatty acid beta
      oxidation (FAO). Malonyl CoA is also a substrate for microsomal fatty acid
      elongation, an important pathway for saturated (SFA), mono- (MUFA) and
      polyunsaturated fatty acid (PUFA) synthesis. Despite the interest in ACC as a
      target for obesity and cancer therapy, little attention has been given to the
      role ACC plays in long chain fatty acid synthesis. This report examines the
      effect of pharmacological inhibition of ACC on DNL and palmitate (16:0) and
      linoleate (18:2, n-6) metabolism in HepG2 and LnCap cells. The ACC inhibitor,
      soraphen A, lowers cellular malonyl CoA, attenuates DNL and the formation of
      fatty acid elongation products derived from exogenous fatty acids, i.e., 16:0 and
      18:2, n-6; IC(50)~5nM. Elevated expression of fatty acid elongases (Elovl5,
      Elovl6) or desaturases (FADS1, FADS2) failed to override the soraphen A effect on
      SFA, MUFA or PUFA synthesis. Inhibition of fatty acid elongation leads to the
      accumulation of 16- and 18-carbon unsaturated fatty acids derived from 16:0 and
      18:2, n-6, respectively. Pharmacological inhibition of ACC activity will not only
      attenuate DNL and induce FAO, but will also attenuate the synthesis of very long
      chain saturated, mono- and polyunsaturated fatty acids.

PMID- 21184749
TI  - Regulation of somatostatin gene expression by brain derived neurotrophic factor
      in fetal rat cerebrocortical cells.
AB  - Brain derived neurotrophic factor (BDNF) increases the levels of somatostatin
      (SS) and its mRNA. To test the hypothesis that the regulation of SS synthesis by
      BDNF occurs at the transcriptional level and requires specific promoter
      sequences, cerebrocortical and PC12trkB neurons were transiently transfected with
      different constructs of the SS promoter fused to the luciferase and CAT reporter
      genes. We demonstrated that BDNF triggered the transcription of the SS gene
      through the CRE sequence located in the SS promoter. BDNF and SS are genes
      regulated by K(+)-induced neuronal activity. Using BDNF blocking antibodies, we
      investigated whether K(+)-induced BDNF was required for K(+)-dependent SS mRNA
      induction. We found that K(+)-induced SS mRNA was partially prevented when BDNF
      was blocked. This finding indicated that BDNF mediated the induction of SS mRNA
      by K(+) depolarization. To identify the mechanisms by which BDNF activates SS
      gene transcription we first elucidated the signaling pathways activated by BDNF
      in cerebrocortical cells. We confirmed that BDNF activates the MAPK/ERKs and
      PI3K/Akt pathways. Both signaling pathways are, in turn, implicated in the
      activation of CREB by BDNF. In addition we observed that the PKA inhibitors, H89
      and Rp-cAMPS decreased BDNF-induced CREB activation. These findings suggested
      that BDNF-induced CREB activation was also mediated by the cAMP/PKA pathway. We
      next elucidated the mechanism by which BDNF induces SS mRNA. We observed that
      H89, PD0998059, KN62 and LY294002 diminished BDNF-induced SS mRNA suggesting that
      BDNF-induced SS mRNA is mediated by the activation of cAMP/PKA, MAPK/ERKs, CaMK
      and PI3K pathways.

PMID- 21184750
TI  - Effect of amniotic-fluid ingestion on vaginal-cervical-stimulation-induced Fos
      expression in female rats during estrus.
AB  - Placental Opioid-Enhancing Factor (POEF) is a substance found in amniotic fluid
      (AF) that, when ingested, potentiates opioid-mediated, but not non-opioid
      mediated, hypoalgesia. Vaginal-cervical stimulation (VCS) produces a stimulus
      bound, partially opioid-mediated hypoalgesia that previous research has shown to
      be potentiated by AF ingestion. To understand the mechanism of opioid enhancement
      by POEF we investigated the pattern of neural activation after a bout of VCS that
      produced hypoalgesia, with and without co-administration of AF. Specifically,
      virgin Long-Evans rats showing vaginal estrus were handled briefly (control) or
      received VCS (75g pressure, 1 min), in a pattern that approximated early
      parturition rather than copulation, using a spring-loaded glass-rod probe. Rats
      were given an orogastric infusion (0.25 ml) of either AF or 0.9% saline resulting
      in four groups (VCS or handling; AF or saline). Rats were perfused 90 min after
      treatment and tissue was processed by immunohistochemistry for Fos. The number of
      Fos-immunoreactive cells was counted in structures previously shown to express
      Fos in response to VCS (the medial preoptic area, MPOA; the ventrolateral portion
      of the ventromedial hypothalamic nucleus, vlVMH; the arcuate nucleus, ARC). We
      found that this pattern of VCS did not produce a significant increase in Fos
      expression in the MPOA and vlVMH unless it was paired with AF. VCS produced a
      significant increase in Fos in the ARC. The interaction of AF and VCS on Fos
      expression in the MPOA suggests that POEF may enhance vaginal-cervical sensory
      input at parturition to facilitate sensitization of the MPOA, and presumably
      facilitate maternal-behavior onset.

PMID- 21184751
TI  - Regio- and stereoselective oxidation of propranolol enantiomers by human CYP2D6,
      cynomolgus monkey CYP2D17 and marmoset CYP2D19.
AB  - Toxic and pharmacokinetic profiles of drug candidates are evaluated in vivo often
      using monkeys as experimental animals, and the data obtained are extrapolated to
      humans. Well understanding physiological properties, including drug-metabolizing
      enzymes, of monkeys should increase the accuracy of the extrapolation. The
      present study was performed to compare regio- and stereoselectivity in the
      oxidation of propranolol (PL), a chiral substrate, by cytochrome P450 2D (CYP2D)
      enzymes among humans, cynomolgus monkeys and marmosets. Complimentary DNAs
      encoding human CYP2D6, cynomolgus monkey CYP2D17 and marmoset CYP2D19 were
      cloned, and their proteins expressed in a yeast cell expression system. The regio
      and stereoselective oxidation of PL enantiomers by yeast cell microsomal
      fractions were compared. In terms of efficiency of expression in the system, the
      holo-proteins ranked CYP2D6=CYP2D17>>CYP2D19. This may be caused by the bulky
      side chain of the amino acid residue at position 119 (leucine for CYP2D19 vs.
      valine for CYP2D6 and CYP2D17), which can disturb the incorporation of the heme
      moiety into the active-site cavity. PL enantiomers were oxidized by all of the
      enzymes mainly into 4-hydroxyproranolol (4-OH-PL), followed by 5-OH-PL and N
      desisopropylpropranolol (NDP). In the kinetic analysis, apparent K(m) values were
      commonly in the MUM range and substrate enantioselectivity of R-PL<S-PL was
      observed in both K(m) and V(max) values for the formation of the three
      metabolites from PL enantiomers. The activity to produce NDP tended to be higher
      for the monkey enzymes, particularly CYP2D17, than for the human enzyme. These
      results indicate that in the oxidation of PL enantiomers by CYP2D enzymes,
      stereoselectivity is similar but regioselectivity is different between humans and
      monkeys.

PMID- 21184752
TI  - Origins of the high catalytic activity of human alcohol dehydrogenase 4 studied
      with horse liver A317C alcohol dehydrogenase.
AB  - The turnover numbers and other kinetic constants for human alcohol dehydrogenase
      (ADH) 4 ("stomach" isoenzyme) are substantially larger (10-100-fold) than those
      for human class I and horse liver alcohol dehydrogenases. Comparison of the
      primary amino acid sequences (69% identity) and tertiary structures of these
      enzymes led to the suggestion that residue 317, which makes a hydrogen bond with
      the nicotinamide amide nitrogen of the coenzyme, may account for these
      differences. Ala-317 in the class I enzymes is substituted with Cys in human
      ADH4, and locally different conformations of the peptide backbones could affect
      coenzyme binding. This hypothesis was tested by making the A317C substitution in
      horse liver ADH1E and comparisons to the wild-type ADH1E. The steady-state
      kinetic constants for the oxidation of benzyl alcohol and the reduction of
      benzaldehyde catalyzed by the A317C enzyme were very similar (up to about 2-fold
      differences) to those for the wild-type enzyme. Transient kinetics showed that
      the rate constants for binding of NAD(+) and NADH were also similar. Transient
      reaction data were fitted to the full Ordered Bi Bi mechanism and showed that the
      rate constants for hydride transfer decreased by about 2.8-fold with the A317C
      substitution. The structure of A317C ADH1E complexed with NAD(+) and 2,3,4,5,6
      pentafluorobenzyl alcohol at 1.2 A resolution is essentially identical to the
      structure of the wild-type enzyme, except near residue 317 where the additional
      sulfhydryl group displaces a water molecule that is present in the wild-type
      enzyme. ADH is adaptable and can tolerate internal substitutions, but the protein
      dynamics apparently are affected, as reflected in rates of hydride transfer. The
      A317C substitution is not solely responsible for the larger kinetic constants in
      human ADH4; thus, the differences in catalytic activity must arise from one or
      more of the other hundred substitutions in the enzyme.

PMID- 21184753
TI  - Polygenetic regression model of renin-angiotensin system genes and the risk of
      coronary artery disease in a large angiographic population.
AB  - BACKGROUND: Polygenetic effect has rarely been addressed in the genetic studies
      of coronary artery disease (CAD). We used the largest and ethnically homogeneous
      angiographic cohort to analyze multilocus data in renin-angiotensin system genes,
      and provide an explicit demonstration of gene-gene interactions. METHODS: A total
      of 1254 consecutive patients who underwent cardiac catheterization (735 with
      coronary artery disease and 519 without) were recruited. Angiotensin converting
      enzyme(ACE) gene I/D polymorphism; T174M, M235T, G-6A, A-20C, G-152A, and G-217A
      polymorphisms of the angiotensinogen (AGT) gene; and A1166C polymorphism of the
      angiotensin II type I receptor (AT1R) gene were genotyped. We used a regression
      approach based on a generalized linear model to evaluate haplotype effects,
      adjust non-genetic confounding effects and detect gene-gene interaction between
      ACE and AT1R genes. RESULTS: We found significant differences in global AGT gene
      haplotype profile and individual haplotypes between cases and controls.
      Significant two-way and three-way gene-gene interactions between ACE I/D, AT1R
      A1166C polymorphisms and AGT gene haplotypes were detected. However, subjects
      carrying both D allele and GGCATC haplotype had an increased risk of CAD (odds
      ratio=1.63 [1.16-2.29]; P=0.004). We also used haplotype counting to directly
      estimate the odds ratio of each specific AGT gene haplotype, and found that the
      effects of haplotypes were markedly different in subgroups with different ACE or
      AT1R gene genotype. CONCLUSIONS: The regression-based haplotype analyses permits
      simultaneous dectection of multi-locus and multi-gene effects in determining the
      risk of CAD. We provide the paradigm for genetic studies of complex-trait
      diseases using candidate genes based on biological pathways.

PMID- 21184754
TI  - PTD4-apoptin protein and dacarbazine show a synergistic antitumor effect on B16
      F1 melanoma in vitro and in vivo.
AB  - PTD4-apoptin protein enters cells and harbors tumor-selective cell death
      activity. Dacarbazine is the mainstay of treatment for malignant melanoma. In
      this study, we investigated the cytotoxic effect of PTD4-apoptin protein and/or
      dacarbazine in mouse B16-F1 and human A875 and SK-MEL-5 melanoma cells in vitro
      and by means of a mouse B16-F1 melanoma model in vivo. PTD4-apoptin protein
      inhibits the growth of B16-F1, A875 and SK-MEL-5 melanoma cells in a dose
      dependent manner, but not in normal human cell lines WI-38 and L-02. PTD4-apoptin
      combined with dacarbazine revealed a synergistic cytotoxic effect (coefficient of
      drug interaction<1) in all three different tumor cell lines. In vivo, PTD4
      apoptin protein and dacarbazine alone effectively inhibited the growth of B16-F1
      melanoma in C57BL/6 mice. Strikingly, combined PTD4-apoptin/dacarbazine treatment
      significantly increased the antitumor effect in comparison to the single
      treatments. As important, a combined PTD4-apoptin/dacarbazine treatment with a
      50% reduction of dacarbazine revealed similar antitumor activities, without
      detectable hematologic side effects. A combined PTD4-apoptin/dacarbazine
      treatment represents a promising novel efficient and safe anticancer strategy.

PMID- 21184755
TI  - Dysfunctions in circadian behavior and physiology in mouse models of Huntington's
      disease.
AB  - Many patients with Huntington's disease (HD) exhibit disturbances in their daily
      cycle of sleep and wake as part of their symptoms. These patients have difficulty
      sleeping at night and staying awake during the day, which has a profound impact
      on the quality of life of the patients and their care-givers. In the present
      study, we examined diurnal and circadian rhythms of four models of HD including
      the BACHD, CAG 140 knock-in and R6/2 CAG 140 and R6/2 CAG 250 lines of mice. The
      BACHD and both R6/2 lines showed profound circadian phenotypes as measured by
      wheel-running activity. Focusing on the BACHD line for further analysis, the
      amplitude of the rhythms in the BACHD mice declined progressively with age. In
      addition, the circadian regulation of heart rate and body temperature in freely
      behaving BACHD mice were also disrupted. Furthermore, the distribution of sleep
      as well as the autonomic regulation of heart rate was disrupted in this HD model.
      To better understand the mechanistic underpinnings of the circadian disruption,
      we used electrophysiological tools to record from neurons within the central
      clock in the suprachiasmatic nucleus (SCN). The BACHD mice exhibit reduced
      rhythms in spontaneous electrical activity in SCN neurons. Interestingly, the
      expression of the clock gene PERIOD2 was not altered in the SCN of the BACHD
      line. Together, this data is consistent with the hypothesis that the HD mutations
      interfere with the expression of robust circadian rhythms in behavior and
      physiology. The data raise the possibility that the electrical activity within
      the central clock itself may be altered in this disease.

PMID- 21184756
TI  - Virus-like particles in Eimeria tenella are associated with multiple RNA
      segments.
AB  - Total nucleic acids from sporulated oocysts of Eimeria tenella isolated from
      Changchun in China were found to contain three extrachromosomal double-stranded
      RNA segments (dsRNAs) of 1.4, 2.4 and 3.6 kb in sizes. These RNAs were resistant
      to RNase A digestion under high salt concentration (0.3 M NaCl). RNA-dependent
      RNA polymerase (RDRP) activity was detected in crude extracts of E. tenella
      sporulated oocysts containing these nucleic acid species. Virus-like particles
      (VLPs) were shown to have a diameter of approximately 38 nm under Electron
      Microscopy (EM) after purification by sucrose density gradient centrifugation. In
      keeping with the nomenclature generally adopted for protozoan viruses, we have
      named this isolate as E. tenella virus (ETV) which is the first virus isolated
      from E. tenella.

PMID- 21184758
TI  - A sensitive sandwich ELISA to measure (1->3)-beta-d-glucan levels in blood.
AB  - A highly sensitive (1->3)-beta-d-glucan (beta-glucan)-specific sandwich ELISA was
      developed using a fragment of recombinant horseshoe crab factor G protein. The
      factor G fragment, which was expressed in Escherichia coli, contains a QQWS
      motif, two beta-glucan-binding domains, and an additional N-terminal cysteine
      residue. The sensitivity of our ELISA was comparable to a conventional (1->3)
      beta-d-glucan detection method using a horseshoe crab-clotting reaction such as
      an amebocyte lysate-based assay. In addition, the beta-glucan levels measured by
      our sandwich ELISA in plasma samples showed a good correlation with those
      measured by the amebocyte lysate-based assay. In the case of our sandwich ELISA,
      it is not necessary to pre-inactivate interfering substances in plasma samples
      that is essential for the conventional amebocyte lysate-based assay. Moreover,
      the assay time of the ELISA method is much shorter than that of the amebocyte
      lysate-based assay. Because of these advantages, the ELISA system will be more
      suitable for high-throughput analysis in clinical laboratories using general
      clinical auto-analyzers. beta-glucan is a typical biomarker for fungal infections
      and the measurements of beta-glucan levels by our ELISA could be useful for the
      diagnosis of fungal infections.

PMID- 21184759
TI  - Performance of a multiplex assay compared to enzyme and precipitation methods for
      anti-ENA testing in systemic lupus and systemic sclerosis.
AB  - INTRODUCTION: Testing for autoantibodies to extractable nuclear antigens (ENA) is
      essential in the investigation of connective tissue disease.
      Counterimmunoelectrophoresis is an early described testing methodology for
      antibodies to ENAs, but is labour-intensive, only moderately sensitive, and
      reliant on high-quality reference sera. Enzyme-linked immunosorbent assay (ELISA)
      is automatable for relatively high sample throughput, but has issues with false
      positives. The addressable laser bead immunoassay (ALBIA) is a multiplex
      technology which can assess several antibody specificities simultaneously on a
      small serum sample. We report performance of an ALBIA system compared with CIE
      and ELISA. METHODS: Samples from 100 systemic sclerosis patients attending Royal
      Free Hospital in 2007 and 99 SLE patients attending St Thomas's Hospital in 2007
      2008 were studied. All samples were tested for antibodies to RNP, Sm, Ro, La, Scl
      70, Jo-1 by in-house CIE, FIDISTM ALBIA (BMD, France), and ELISAs (Phadia,
      Germany). Cohen's kappa coefficient was used to examine agreement of the
      different assay methods for the same antibody. McNemar's test was used to detect
      differences between methodologies. RESULTS: One sample was positive for anti-Jo-1
      by CIE, & confirmed by ALBIA & ELISA. All 198 remaining samples were anti-Jo-1
      negative by all 3 methods. With respect to RNP, Ro, La, Scl-70 antibodies, there
      was good agreement in assay performance between CIE, ALBIA, and ELISA. For Sm,
      agreement was less good between CIE and ELISA (kappa 0.491), and ALBIA and ELISA
      (kappa 0.403). Using McNemar's test performance was no different between the 3
      assays, with the following exceptions: between CIE and ELISA for Ro-60 (p<0.01)
      and RNP (p<0.05), and between ALBIA and ELISA for RNP (p<0.01). CONCLUSIONS: The
      FIDISTM ALBIA produced similar level of performance as CIE, but with advantages
      of automation, and less dependence on highly skilled operators. ALBIA represents
      a potential advancement applicable to routine Immunology diagnostics.

PMID- 21184757
TI  - Increasing prevalence of HCC and cirrhosis in patients with chronic hepatitis C
      virus infection.
AB  - BACKGROUND & AIMS: Patients with hepatitis C virus (HCV) infection are at risk
      for developing costly and morbid complications, although the actual prevalence of
      these complications is unknown. We examined time trends in the prevalence of
      cirrhosis and its related complications, such as hepatic decompensation and
      hepatocellular carcinoma (HCC). METHODS: We calculated the annual prevalence of
      cirrhosis, decompensated cirrhosis, and HCC in a national sample of veterans
      diagnosed with HCV between 1996 and 2006. Patients with HCV who had at least one
      physician visit in a given calendar year were included in the analysis of
      prevalence for that year. We used direct standardization to adjust the prevalence
      of cirrhosis and related complications for increasing age of the cohort as well
      as sex and changes in clinical characteristics. RESULTS: In this cohort, the
      number of individuals with HCV increased from 17,261 in 1996 to 106,242 in 2006.
      The prevalence of cirrhosis increased from 9% in 1996 to 18.5% in 2006. The
      prevalence of patients with decompensated cirrhosis doubled, from 5% in 1996 to
      11% in 2006, whereas the prevalence of HCC increased approximately 20-fold (0.07%
      in 1996 to 1.3% in 2006). After adjustment, the time trend in the prevalence of
      cirrhosis (and its complications) was lower than the crude trend, although it
      still increased significantly. CONCLUSIONS: The prevalence of cirrhosis and HCC
      in HCV-infected patients has increased significantly over the past 10 years. An
      aging cohort of patients with HCV could partly explain our findings. Clinicians
      and health care systems should develop strategies to provide timely and effective
      care to this high-risk population of patients.

PMID- 21184760
TI  - Kinetic models of guanidine hydrochloride-induced curing of the yeast [PSI+]
      prion.
AB  - A population of [PSI(+)] Saccharomyces cerevisiae cells can be cured of the
      [PSI(+)] prion by the addition of guanidine hydrochloride (GdnHCl). In this paper
      we extend existing nucleated polymerisation simulation models to investigate the
      mechanisms that might underlie curing. Our results are consistent with the belief
      that prions are dispersed through the cells at division following GdnHCl
      addition. A key feature of the simulation model is that the probability that a
      polymer is transmitted from mother to daughter during cell division is dependent
      upon the length of the polymer. The model is able to reproduce the essential
      features of data from several different experimental protocols involving addition
      and removal of GdnHCl.

PMID- 21184761
TI  - Spatio-temporal modelling of the Hes1 and p53-Mdm2 intracellular signalling
      pathways.
AB  - The correct localisation of transcription factors is vitally important for the
      proper functioning of many intracellular signalling pathways. Experimental data
      has shown that many pathways exhibit oscillations in concentrations of the
      substances involved, both temporally and spatially. Negative feedback loops are
      important components of these oscillations, providing fine regulation for the
      factors involved. In this paper we consider mathematical models of two such
      pathways-Hes1 and p53-Mdm2. Building on previous mathematical modelling
      approaches, we derive systems of partial differential equations to capture the
      evolution in space and time of the variables in the Hes1 and p53-Mdm2 systems.
      Through computational simulations we show that our reaction-diffusion models are
      able to produce sustained oscillations both spatially and temporally, accurately
      reflecting experimental evidence and advancing previous models. The simulations
      of our models also allow us to calculate a diffusion coefficient range for the
      variables in each mRNA and protein system, as well as ranges for other key
      parameters of the models, where sustained oscillations are observed. Finally, by
      exploiting the explicitly spatial nature of the partial differential equations,
      we are also able to manipulate mathematically the spatial location of the
      ribosomes, thus controlling where the proteins are synthesized within the
      cytoplasm. The results of these simulations predict an optimal distance outside
      the nucleus where protein synthesis should take place in order to generate
      sustained oscillations. Using partial differential equation models, new
      information can be gained about the precise spatio-temporal dynamics of mRNA and
      proteins. The ability to determine spatial localisation of proteins within the
      cell is likely to yield fresh insight into a range of cellular diseases such as
      diabetes and cancer.

PMID- 21184762
TI  - Regulation of cell cycle and DNA repair in post-mitotic GABA neurons in psychotic
      disorders.
AB  - Disturbances of cell cycle regulation and DNA repair in post-mitotic neurons have
      been implicated in degenerative and malignant diseases of the human brain. Recent
      work is now suggesting that abnormal regulation of these functions in GABA cells
      of the adult hippocampus may also play a role in two neuropsychiatric disorders.
      In schizophrenia and bipolar disorder, a network of genes involved in the
      regulation of GAD67, a marker for the functional differentiation of GABA cells,
      show pronounced changes in expression and include kainate receptor subunits,
      TGFbeta and Wnt signaling pathways, epigenetic factors and transcription factors.
      One of these genes, cyclin D2, is involved in the regulation of cell cycle and
      DNA repair and appears to be a pivotal element in linking GAD67 expression with
      these functional clusters of genes. Dysfunction of post-mitotic GABAergic neurons
      in the adult hippocampus of patients with psychotic disorders is associated with
      changes in the expression of genes that are involved in the maintenance of
      functional and genomic integrity of GABA cells. The nature of these changes is
      quite different in schizophrenia and bipolar disorder, suggesting that a common
      cell phenotype (in this case, decreased GAD67 expression) may involve two
      fundamentally different molecular endophenotypes and reflect unique
      susceptibility genes involved in the respective disorders. This article is part
      of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio
      Costa'.

PMID- 21184763
TI  - Nociceptin/orphanin FQ receptor knockout rats: in vitro and in vivo studies.
AB  - Nociceptin/orphanin FQ (N/OFQ) regulates several biological functions via
      selective activation of the N/OFQ peptide (NOP) receptor. Recently knockout rats
      for the NOP receptor gene (NOP(-/-)) have been generated; these animals were used
      in the present study to investigate their emotional (open field, elevated plus
      maze, and forced swimming test), locomotor (drag and rotarod test), and
      nociceptive (plantar and formalin test) phenotypes in comparison with their
      NOP(+/+) littermates. In addition, N/OFQ sensitivity has been assessed in
      electrically stimulated vas deferens tissues taken from NOP(+/+) and NOP(-/-)
      rats. In the elevated plus maze and forced swimming tests NOP(-/-) rats showed
      anxiety- and anti-depressant-like phenotype, respectively. No differences were
      found in the open field test. NOP(-/-) rats outperformed their NOP(+/+)
      littermates in two motor behaviour assays. Genetic ablation of the NOP receptor
      gene produced a statistically significant increase in nociceptive behaviour of
      the mutant rats in the formalin test. Finally, in the electrically stimulated rat
      vas deferens taken from NOP(+/+) tissues, N/OFQ inhibited in a concentration
      dependent manner the electrically induced twitches while the peptide was inactive
      in tissues taken from NOP(-/-) animals. These results, in line with previous
      findings obtained with selective NOP receptor antagonists in mice and rats and
      with mouse knockout studies, clearly indicate that endogenous N/OFQ-NOP receptor
      signalling plays an important role in controlling anxiety- and mood-related
      behaviours, exercise-driven locomotor activity and nociception. These
      observations are relevant for defining the therapeutic indications (and
      contraindications) of NOP receptor antagonists.

PMID- 21184765
TI  - Stimulation at dorsal and ventral electrode contacts targeted at the subthalamic
      nucleus has different effects on motor and emotion functions in Parkinson's
      disease.
AB  - Motor and emotion processing depend on different fronto-basal ganglia circuits.
      Distinct sub-regions of the subthalamic nucleus (STN) may modulate these
      circuits. We evaluated whether stimulation targeted at separate territories in
      the STN region would differentially affect motor and emotion function. In a
      double-blind design, we studied twenty Parkinson's disease patients who had deep
      brain stimulation (DBS) electrodes implanted bilaterally in the STN. We
      stimulated either dorsal or ventral contacts of the STN electrodes on separate
      days in each patient and acquired behavioral measures. Dorsal contact stimulation
      improved motor function by reducing scores on the Unified Parkinson's Disease
      Rating Scale and by reducing both reaction time and reaction time variability
      compared to ventral contact stimulation. By contrast, ventral contact stimulation
      led to an increase in positive emotion compared to dorsal contact stimulation.
      These results support the hypothesis that different territories within the STN
      region implement motor and emotion functions.

PMID- 21184764
TI  - Influence of early attentional modulation on working memory.
AB  - It is now established that attention influences working memory (WM) at multiple
      processing stages. This liaison between attention and WM poses several
      interesting empirical questions. Notably, does attention impact WM via its
      influences on early perceptual processing? If so, what are the critical factors
      at play in this attention-perception-WM interaction. I review recent data from
      our laboratory utilizing a variety of techniques (electroencephalography (EEG),
      functional MRI (fMRI) and transcranial magnetic stimulation (TMS)), stimuli
      (features and complex objects), novel experimental paradigms, and research
      populations (younger and older adults), which converge to support the conclusion
      that top-down modulation of visual cortical activity at early perceptual
      processing stages (100-200 ms after stimulus onset) impacts subsequent WM
      performance. Factors that affect attentional control at this stage include
      cognitive load, task practice, perceptual training, and aging. These developments
      highlight the complex and dynamic relationships among perception, attention, and
      memory.

PMID- 21184767
TI  - (Arene)Cl2Ru(II) complexes with N-coordinated estrogen and androgen
      isonicotinates: interaction with sex hormone binding globulin and anticancer
      activity.
AB  - (Arene)dichloridoruthenium(II) complexes with N-coordinated isonicotinates of
      androgens (6) and estrogens (9) were prepared and tested for affinity to the
      estrogen receptor (ERalpha) and sex hormone binding globulin (SHBG), as well as
      for cytotoxicity in cancer cells. None of the new complexes bound noticeably to
      the ER and most of them also bound less strongly to SHBG than the corresponding
      unmetallated steroids 7. In MTT assays the Ru(p-cymene) complexes 9 of 2
      substituted estrones were equally or even more cytotoxic than the metal-free
      steroids against hormone-dependent (MCF-7 breast and KB-V1 cervix carcinomas) and
      hormone-independent (518A2 melanoma) cells. The addition of external SHBG to MTT
      assays lowered the cytotoxicities of the complexes 9 and distinctly more so those
      of some steroids 7, probably by the way of sequestration and reduction of the
      cellular uptake. In the absence of SHBG the estrogen complexes 9 were
      internalized by 518A2 melanoma cells and ruthenated their DNA as quantified by
      ICP-OES. They also ruthenated salmon sperm DNA but did not change the topology of
      plasmid DNA in EMSA experiments. In addition, the Ru(p-cymene) complex of 2
      ethoxyestrone (9c) was shown to reduce the motility of 518A2 melanoma cells in a
      wound-healing assay.

PMID- 21184766
TI  - Nitrous oxide causes a regulated hypothermia: rats select a cooler ambient
      temperature while becoming hypothermic.
AB  - An initial administration of 60% nitrous oxide (N(2)O) evokes hypothermia in rats
      and if the administration continues for more than 1-2h, acute tolerance typically
      develops such that the initial reduction in core temperature (Tc) reverses and Tc
      recovers toward control values. Calorimeter studies at normal ambient temperature
      indicate that hypothermia results from a transient reduction in heat production
      (HP) combined with an elevation in heat loss. Acute tolerance develops primarily
      due to progressive increases in HP. Our aim was to determine whether rats
      provided a choice of ambient temperatures would behaviorally facilitate or oppose
      N(2)O-induced hypothermia. A gas-tight thermally-graded alleyway (range, 6.7-37.0
      degrees C) enabled male Long-Evans rats (n=12) to select a preferred ambient
      temperature during a 5-hour steady-state administration of 60% N(2)O and a
      separate paired control gas exposure (order counterbalanced). Tc was measured
      telemetrically from a sensor surgically implanted into the peritoneal cavity
      >7days before testing. Internal LED lighting maintained the accustomed day:night
      cycle (light cycle 0700-1900h) during sessions lasting 45.5h. Rats entered the
      temperature gradient at 1100h, and the 5-h N(2)O or control gas period did not
      start until 23h later to provide a long habituation/training period. Food and
      water were provided ad libitum at the center of the alleyway. The maximum
      decrease of mean Tc during N(2)O administration occurred at 0.9h and was -2.05+/
      0.25 degrees C; this differed significantly (p<0.0001) from the corresponding Tc
      change at 0.9h during control gas administration (0.01+/-0.14 degrees C). The
      maximum decrease of the mean selected ambient temperature during N(2)O
      administration occurred at 0.7h and was -13.58+/-1.61 degrees C; this differed
      significantly (p<0.0001) from the corresponding mean change in the selected
      ambient temperature at 0.7h during control gas administration (0.30+/-1.49
      degrees C). N(2)O appears to induce a regulated hypothermia because the selection
      of a cool ambient temperature facilitates the reduction in Tc. The recovery of Tc
      during N(2)O administration (i.e., acute tolerance development) could have been
      facilitated by selection of ambient temperatures that were warmer than those
      chosen during control administrations, but interestingly, this did not occur.

PMID- 21184768
TI  - Novel role of signal transducer and activator of transcription 3 as a
      progesterone receptor coactivator in breast cancer.
AB  - Interactions between progesterone receptor (PR) and signal transducer and
      activator of transcription 3 (Stat3)-mediated signaling pathways have already
      been described. In the present study, we explored the capacity of Stat3 to
      functionally interact with progesterone receptor (PR) and modulate PR
      transcriptional activation in breast cancer cells. We found that the synthetic
      progestin medroxyprogesterone acetate (MPA) induced the association of a PR/Stat3
      complex in which Stat3 acts as a coactivator of PR. We demonstrated that Stat3
      activation is required for MPA modulation of the endogenous genes bcl-X and
      p21(CIP1) which are involved in MPA-induced cell cycle regulation. Stat3 activity
      as a coactivator of PR was observed in both the classical and nonclassical ligand
      activated-PR transcriptional mechanisms, since the effects described were
      identified in the bcl-X promoter which contains a progesterone responsive element
      and in the p21(CIP1) promoter which carries Sp1 binding sites where PR is
      recruited via the transcription factor Sp1. The data herein presented identifies
      a potential therapeutic intervention for PR-positive breast tumors consisting of
      targeting Stat3 function or PR/Stat3 interaction which will result in the
      inhibition of PR function.

PMID- 21184770
TI  - Rock squirrel (Spermophilus variegatus) blood sera affects proteolytic and
      hemolytic activities of rattlesnake venoms.
AB  - Rock squirrels (Spermophilus variegatus) from two sites in south central New
      Mexico, where prairie (Crotalus viridis viridis) and western diamondback
      (Crotalus atrox) rattlesnakes are common predators, were assayed for inhibition
      of rattlesnake venom digestive and hemostatic activities. At statistically
      significant levels rock squirrel blood sera reduced the metalloprotease and
      hemolytic activity of venoms from C. v. viridis and C. atrox more than venom from
      an allopatric snake species, the northern Pacific rattlesnake (Crotalus
      oreganus). In contrast, general proteolytic activity of venom from C. oreganus
      was inhibited more by S. variegatus serum defenses than activity of venom from
      sympatric snakes. For all three venoms, incubation with squirrel sera increased
      the level of fibrinolysis over venom-only treatments. These results suggest that
      rock squirrels (S. variegatus) can defend against metalloproteases and other
      proteases after envenomation from at least two of five rattlesnake predators they
      might encounter. However, there were statistically significant differences
      between general proteolytic activity and fibrinolytic activity of C. v. viridis
      and C. atrox venom, suggesting that rock squirrels might be differentially
      vulnerable to these two predators. The hypothesis that prey resistance influences
      snake venom evolution in a predator-prey arms race is given further support by
      the previously cryptic variation in venoms detected when assayed against prey
      defenses.

PMID- 21184769
TI  - Identification of amino acids critical for the cytotoxicity of Shiga toxin 1 and
      2 in Saccharomyces cerevisiae.
AB  - Shiga toxins (Stx1 and Stx2) are produced by E. coli O157:H7, which is a leading
      cause of foodborne illness. The A subunits of Stx1 (Stx1A) and Stx2 (Stx2A) are
      ribosome inactivating proteins (RIPs) that inhibit translation by removing an
      adenine from the highly conserved alpha-sarcin ricin loop (SRL) of the large
      rRNA. Here, we used mutagenesis in Saccharomyces cerevisiae to identify residues
      critical for cytotoxicity of Stx1A and Stx2A. The A subunits depurinated the SRL,
      inhibited translation and caused apoptotic-like cell death in yeast. Single
      mutations in Asn75, Tyr77, Glu167 and Arg176 reduced the cytotoxicity of both
      toxins around 10-fold. However, Asn75 and Tyr77 were more critical for the
      depurination activity of Stx2A, while Arg176 was more critical for the
      depurination activity of Stx1A. The crystal structures of the two proteins lack
      electron density for some surface loops, including one which is adjacent to the
      active site in both molecules. Modeling these loops changed neither the secondary
      nor the tertiary structures of the rest of the protein. Analysis of solvent
      accessible surface areas indicated that Asn75 and Tyr77 are more exposed in
      Stx2A, while Arg176 is more exposed in Stx1A, indicating that residues with
      higher surface exposure were more critical for enzymatic activity. Double
      mutations at Glu167 and Arg176 eliminated the depurination activity and
      cytotoxicity of both toxins. C-terminal deletions of A chains eliminated
      cytotoxicity of both toxins, but showed functional differences. Unlike Stx1A,
      cytotoxicity of Stx2A was lost before its ability to depurinate ribosomes. These
      results identify residues that affect enzymatic activity and cytotoxicity of
      Stx1A and Stx2A differently and demonstrate that the function of these residues
      can be differentiated in yeast. The extent of ribosome depurination and
      translation inhibition did not correlate with the extent of cell death,
      indicating that depurination of the SRL and inhibition of translation are not
      entirely responsible for cell death.

PMID- 21184771
TI  - Allicin from garlic neutralizes the hemolytic activity of intra- and extra
      cellular pneumolysin O in vitro.
AB  - Pneumolysin (PLY) is a key virulence factor contributes to the pathogenesis of
      Streptococcus pneumoniae. In this study we investigated the effect of allicin and
      aqueous garlic extracts on hemolytic activity of PLY both in prelysed and intact
      cells. Additionally the antimicrobial activity of allicin was tested against the
      bacteria. All tested materials potently inhibited the PLY hemolytic activity.
      Allicin neutralizes PLY in a concentration- and time-dependent manner. Twenty
      five minute incubation of PLY (2 HU/mL) with 0.61 MUM/mL concentration of
      allicin, totally inhibited hemolytic activity of PLY (IC50 = 0.28 MUM/mL). The
      inhibitory activity of old extract of garlic was similar to pure allicin (IC50 =
      50.46 MUL/mL; 0.31 MUM/mL; P < 0.05). In contrast fresh extract of garlic
      inhibits the PLY hemolytic activity at lower concentrations (IC50 = 13.96 MUL/mL;
      0.08 MUM/mL allicin). Exposure of intact cells to allicin (1.8 MUM) completely
      inhibited hemolytic activity of PLY inside bacterial cells. The inhibitory effect
      of the allicin was restored by addition of reducing agent DTT at 5 mM, proposing
      that allicin likely inhibits the PLY by binding to cysteinyl residue in the
      binding site. The MIC value of allicin was determined to be 512 MUg/mL (3.15
      MUM/mL). These results indicate that PLY is a novel target for allicin and may
      provide a new line of investigation on pneumococcal diseases in the future.

PMID- 21184772
TI  - Drug development from Australian elapid snake venoms and the Venomics pipeline of
      candidates for haemostasis: Textilinin-1 (Q8008), HaempatchTM (Q8009) and
      CoVaseTM (V0801).
AB  - Snake venoms are attractive for drug discovery and development, with a number of
      therapeutics derived from snake venom either in clinical use or in development.
      Recognising this opportunity, Australian biopharmaceutical company QRxPharma Ltd
      and its subsidiary Venomics Pty Ltd (VPL) has partnered with the University of
      Queensland (UQ) to screen and develop drug candidates from Australian elapid
      snake venoms. VPL has three haemostasis candidates in early preclinical
      development. Textilinin-1 (Q8008) is a 7 kDa potent and selective plasmin
      inhibitor that has application as an anti-fibrinolytic agent to reduce blood loss
      associated with complex surgeries. HaempatchTM (Q8009) is a Factor Xa-like
      protein that displays potent procoagulant effects and is being developed as a
      topical haemostatic agent to reduce blood loss resulting from surgery or trauma.
      CoVaseTM (V0801) is a procoagulant cofactor that may have application as a
      systemic anti-bleeding agent in the treatment of internal bleeding and non
      compressible haemorrhage. This review focuses on drug discovery from Australian
      elapid snake venoms, with emphasis on the QRxPharma/VPL drug discovery project
      undertaken in collaboration with UQ and candidates at further stages of
      development.

PMID- 21184773
TI  - Progressive age-dependent DNA methylation changes start before adulthood in mouse
      tissues.
AB  - Changes in DNA methylation during aging have implications for various age-related
      diseases. While the deleterious effects of age-dependent methylation changes
      after adulthood have attracted the attention of researchers, the relationship
      between those changes and changes that occur before adulthood have not been
      focused on. In this study, dozens of CpG sites whose methylation status changed
      after adulthood were identified in the mouse muscle, brain, and liver, by
      analysis of the methylation status of 316 CpG sites located within -7 to 3 kb of
      the transcription start sites (TSS-flanking regions) of 350 genes. Although the
      majority of the methylation changes were tissue-specific, two characteristics
      were observed in the methylation changes of each tissue. First, most DNA
      methylation changes after adulthood were preceded by prominent and same-direction
      DNA methylation changes before adulthood, and second, the expression levels of
      genes near progressively methylated and demethylated CpG sites were already
      significantly low and high, respectively, in young mice. The latter finding was
      also confirmed by analyzing recently published data of genome-wide age-dependent
      methylation changes. These results suggest that the DNA methylation status
      consistently move toward development/maturation throughout lifespan, and the
      tissue-dependent epigenetic or transcriptional status underlies the methylation
      changes.

PMID- 21184774
TI  - Increase in formalin-induced tonic pain by 5alpha-reductase and aromatase
      inhibition in female rats.
AB  - Little is known about the role of steroidogenic enzymes in pain modulation. This
      study examined the effects of 5alpha-reductase and aromatase inhibition on
      formalin-induced tonic pain (FITP) in adult female rats. The animals received
      subcutaneous injection (5 mg/kg) of finasteride (an inhibitor of 5alpha
      reductase) and letrozole (an inhibitor of aromatase), either separately or in
      combination, 15 min before formalin injection at a low (0.25%) and high (2.5%)
      concentration. Pretreatment with inhibitors increased FITP evoked by injection of
      0.25% formalin, but they were not effective on 2.5% formalin pain. The enhancing
      effects of finasteride and letrozole on FITP induced by 2.5% formalin was
      demonstrated by inhibitory actions of these drugs on morphine (7 and 10 mg/kg,
      intraperitoneal) induced antinociception. The nervous system could be considered
      as the main target of the enzymes inhibition, since the pronociceptive effect was
      also observed after administration of inhibitors to ovariectomized rats.
      Altogether, these findings suggest that the biological activity of the enzymes
      5alpha-reductase and aromatase modulates FITP and may help to develop effective
      therapeutic strategies to counteract pain.

PMID- 21184775
TI  - Ethanol-induced sensitization depends preferentially on D1 rather than D2
      dopamine receptors.
AB  - Behavioral sensitization, defined as a progressive increase in the locomotor
      stimulant effects elicited by repeated exposure to drugs of abuse, has been used
      as an animal model for drug craving in humans. The mesoaccumbens dopaminergic
      system has been proposed to be critically involved in this phenomenon; however,
      few studies have been designed to systematically investigate the effects of
      dopaminergic antagonists on development and expression of behavioral
      sensitization to ethanol in Swiss mice. We first tested the effects of D(1)
      antagonist SCH-23390 (0-0.03 mg/kg) or D(2) antagonist Sulpiride (0-30 mg/kg) on
      the locomotor responses to an acute injection of ethanol (2.0 g/kg). Results
      showed that all tested doses of the antagonists were effective in blocking
      ethanol's stimulant effects. In another set of experiments, mice were pretreated
      intraperitoneally with SCH-23390 (0.01 mg/kg) or Sulpiride (10 mg/kg) 30 min
      before saline or ethanol injection, for 21 days. Locomotor activity was measured
      weekly for 20 min. Four days following this pretreatment, all mice were
      challenged with ethanol. Both antagonists attenuated the development of ethanol
      sensitization, but only SCH-23390 blocked the expression of ethanol sensitization
      according to this protocol. When we tested a single dose (30 min before tests) of
      either antagonist in mice treated chronically with ethanol, both antagonists
      attenuated ethanol-induced effects. The present findings demonstrate that the
      concomitant administration of ethanol with D(1) but not D(2) antagonist prevented
      the expression of ethanol sensitization, suggesting that the neuroadaptations
      underlying ethanol behavioral sensitization depend preferentially on D(1)
      receptor actions.

PMID- 21184777
TI  - Isolation and in vitro characterisation of prohaemocytes from the spider crab,
      Hyas araneus (L.).
AB  - A population of small, mostly undifferentiated, haemocytes were identified and
      enriched from the circulation of the spider crab, H. araneus, using a two-step
      density gradient separation procedure. Typically, these cells are spherical, ca.
      8-12 MUm diameter and have a high nucleus:cytoplasm ratio. Their number in the
      circulation increases significantly 24 h after a state of haemocytopenia has been
      created by withdrawal of 2 mL of haemolymph. The rise in the number of these
      cells at this time is consistent with a left shift phenomenon. A two-step
      separation procedure was developed to generate enriched populations of these
      small cells from the haemolymph and in vitro assays revealed that ca. 47% are
      BrdU-positive in vitro. By contrast BrdU uptake was not observed in the hyaline,
      semigranular or granular cells. The proliferative ability of the small cells,
      coupled with their close morphological resemblance to immature haemocytes
      reported from the haematopoietic tissue of other decapod species, leads us to
      conclude that these cells are prohaemocytes.

PMID- 21184776
TI  - Characterization of the novel antibacterial peptide Leucrocin from crocodile
      (Crocodylus siamensis) white blood cell extracts.
AB  - Four novel antibacterial peptides, Leucrocin I-IV from Siamese crocodile white
      blood cell extracts were purified by reverse phase high performance liquid
      chromatography (RP-HPLC). Leucrocins exhibit strong antibacterial activity
      towards Staphylococcus epidermidis, Salmonella typhi and Vibrio cholerae. The
      peptides were 7-10 residues in length with different primary structure. The amino
      acid sequence of Leucrocin I is NGVQPKY with molecular mass around 806.99 Da and
      Leucrocin II is NAGSLLSGWG with molecular mass around 956.3 Da. Further, the
      interaction between peptides and bacterial membranes as part of their killing
      mechanism was studied by fluorescence and electron microscopy. The outer membrane
      and cytoplasmic membrane was the target of action of Leucrocins as assayed in
      model membrane by release of beta-galactosidase due to the membrane
      permeabilization. Finally, the hemolytic effect was tested against human red
      blood cell. Leucrocin I, III and IV showed less toxicity against human red blood
      cells than Leucrocin II.

PMID- 21184778
TI  - Cross-species affective functions of the medial forebrain bundle-implications for
      the treatment of affective pain and depression in humans.
AB  - Major depression (MD) might be conceptualized as pathological under-arousal of
      positive affective systems as parts of a network of brain regions assessing,
      reconciling and storing emotional stimuli versus an over-arousal of parts of the
      same network promoting separation-distress/GRIEF. In this context depression can
      be explained as an emotional pain state that is the result of a disregulation of
      several sub-systems that under physiological conditions are concerned with bodily
      or emotional homeostasis of the human organism in a social context.
      Physiologically, homeostasis is maintained by influences of the SEEKING system
      represented - amongst others - by the medial forebrain bundle (MFB). Neuroimaging
      studies show that the MFB has a proven access to the GRIEF/Sadness system. A
      functional decoupling of these systems with a dysfunctional GRIEF pathway might
      result in MD. Therewith GRIEF and SEEKING/PLEASURE systems play important roles
      as opponents in maintenance of emotional homeostasis. Chronic electrical
      modulation of the reward SEEKING pathways with deep brain stimulation might show
      anti-depressive effects in humans suffering from MD by re-initiating an emotional
      equilibrium (of higher or lower activity) between these opposing systems.

PMID- 21184779
TI  - MDMA ("ecstasy") abuse as an example of dopamine neuroplasticity.
AB  - A number of reviews have focused on the short- and long-term effects of MDMA and,
      in particular, on the persistent deficits in serotonin neurotransmission that
      accompany some exposure regimens. The mechanisms underlying the serotonin
      deficits and their relevance to various behavioral and cognitive consequences of
      MDMA use are still being debated. It has become clear, however, that some
      individuals develop compulsive and uncontrolled drug-taking that is consistent
      with abuse. For other drugs of abuse, this transition has been attributed to
      neuroadaptations in central dopamine mechanisms that occur as a function of
      repeated drug exposure. A question remains as to whether similar neuroadaptations
      occur as a function of exposure to MDMA and the impact of serotonin neurotoxicity
      in the transition from use to abuse. This review focuses specifically on this
      issue by first providing an overview of human studies and then reviewing the
      animal literature with specific emphasis on paradigms that measure subjective
      effects of drugs and self-administration as indices of abuse liability. It is
      suggested that serotonin deficits resulting from repeated exposure to MDMA self
      administration lead to a sensitized dopaminergic response to the drug and that
      this sensitized response renders MDMA comparable to other drugs of abuse.

PMID- 21184780
TI  - Automated and quantitative image analysis of ischemic dendritic blebbing using in
      vivo 2-photon microscopy data.
AB  - Ischemia induces a 'blebbing' of dendrites, a structural alteration where
      dendrites take on a 'beads on a string' appearance. We developed a toolkit
      program, BlebQuant, for quantitative automated bleb analysis to chart the
      morphology of dendrites labeled with GFP/YFP under normal conditions and after
      ischemia-induced damage. In vivo 2-photon data from mouse layer 5 neurons with
      apical dendritic tufts extending to the cortical surface were examined before,
      during, and after global ischemia. To quantify changes in dendritic structure, we
      used morphometric tools that exploit characteristic features of blebbing,
      distinguished as localized regions of spherical or ellipsoid swellings. By
      comparing acquired images during ischemia and reperfusion to a pre-ischemia
      reference image, our automated approach detected blebs based on defined
      eccentricity and area thresholds and quantified the percentage of blebbed
      dendrites based on a block-selection method. Our results indicate that the
      automated morphometric indices we employ yield results that correlate with manual
      assessment. The automated approach permits rapid and effective analysis of
      dendritic structure and may facilitate the study of ischemic dendritic damage.

PMID- 21184781
TI  - Time-varying model identification for time-frequency feature extraction from EEG
      data.
AB  - A novel modelling scheme that can be used to estimate and track time-varying
      properties of nonstationary signals is investigated. This scheme is based on a
      class of time-varying AutoRegressive with an eXogenous input (TVARX) models where
      the associated time-varying parameters are represented by multi-wavelet basis
      functions. The orthogonal least square (OLS) algorithm is then applied to refine
      the model parameter estimates of the TVARX model. The main features of the multi
      wavelet approach is that it enables smooth trends to be tracked but also to
      capture sharp changes in the time-varying process parameters. Simulation studies
      and applications to real EEG data show that the proposed algorithm can provide
      important transient information on the inherent dynamics of nonstationary
      processes.

PMID- 21184782
TI  - Alcohol seeking and consumption in the NVHL neurodevelopmental rat model of
      schizophrenia.
AB  - Alcohol abuse in schizophrenia exceeds rates in the general population and
      worsens illness outcomes. Neonatal ventral hippocampal lesion (NVHL) rats model
      multiple schizophrenia dimensions including addiction vulnerability. This study
      compared NVHL vs. SHAM-controls in operant alcohol seeking and consumption. NVHLs
      enhanced consumption of combined ethanol/sucrose solution but neither ethanol or
      sucrose only solutions, consistent with increased vulnerability specific to
      carbohydrate-laden alcohol beverages typically consumed in early stages of human
      alcoholism.

PMID- 21184783
TI  - Anger and cardiovascular startle reactivity in normotensive young males.
AB  - Anger has been implicated in the etiology of hypertensive disease. Trait anger
      has been linked to enhanced cardiovascular responsiveness. However, whether this
      association reflects differences in context appraisal or a general hyper
      reactivity of the cardiovascular system remains unclear. We studied the
      cardiovascular response to acoustic startle probes in 76 healthy Caucasian males
      in different affective contices (pleasant, neutral, and unpleasant). All
      participants completed the State-Trait-Anger-Expression-Inventory (STAXI) by
      Spielberger and the results were analysed with stepwise regression analysis
      according to the anger scores and traditional risk factors for hypertension. Our
      study reveals differential modulation of the cardiovascular response to startle
      stimuli by affective pictures in the dimensions "valence" for heart rate and
      "arousal" for blood pressure. Anger-in was identified as the most important
      determinant for blood pressure responses in unpleasant context, while anger-out
      was associated with less cardiovascular activation in neutral context. This is
      the first study that relates trait anger to cardiovascular reactivity and
      affective reflex modulation in normotensive subjects. We could demonstrate an
      interaction of affective context and trait anger for cardiovascular (hyper
      )reactivity. Increased cardiovascular reactivity for higher scores of anger-in in
      unpleasant context may indicate enhanced sympathetic reactivity and constitute a
      risk factor for the development of essential hypertension.

PMID- 21184784
TI  - Distinct role of endocytosis for Smad and non-Smad TGF-beta signaling regulation
      in hepatocytes.
AB  - BACKGROUND & AIMS: In injured liver, TGF-beta affects all hepatic cell types and
      participates in wound healing and fibrogenesis. TGF-beta downstream signaling is
      highly complex and cell type dependent, involving Smad and non-Smad signaling
      cascades thus requiring tight regulation. Endocytosis has gained relevance as
      important mechanism to control signaling initiation and termination. In this
      study, we investigated endocytic mechanisms for TGF-beta mediated Smad and non
      Smad signaling in hepatocytes. METHODS: Endocytosis in hepatocytes was elucidated
      using chemical inhibitors, RNAi, viral gene transfer and caveolin-1-/- mice. TGF
      beta signaling was monitored by Western blot, reporter assays and gene expression
      analysis. RESULTS: In hepatocytes, Smad activation is to a large degree
      accomplished AP-2 complex dependent on the hepatocyte surface without the
      necessity of clathrin coated pit formation or an endocytic step. In contrast, non
      Smad/AKT pathway activation required functional dynamin mediated endocytosis and
      the presence of caveolin-1, an essential protein for caveolae formation.
      Furthermore, these two TGF-beta signaling initiation platforms discriminate
      distinct signaling routes that integrate at the transcriptional level as shown
      for TGF-beta target genes, Id1, Smad7, and CTGF. Endocytosis inhibition increased
      canonical Smad signaling and culminated in a superinduction of Id1 and Smad7
      expression, whereas caveolin-1 mediated AKT pathway activation was required for
      maximal CTGF induction. CONCLUSIONS: Endocytosis is critical for TGF-beta
      signaling regulation in hepatocytes and determines gene expression signature and
      (patho)physiological outcome.

PMID- 21184785
TI  - Diabetes is a progression factor for hepatic fibrosis in a high fat fed mouse
      obesity model of non-alcoholic steatohepatitis.
AB  - BACKGROUND & AIMS: While type 2 diabetes is an independent risk factor for
      worsening of human non-alcoholic steatohepatitis (NASH) in clinical studies, it
      has not been systematically reported in any model whether diabetes exacerbates
      NASH. The study aim was to determine if diabetes causes NASH progression in a
      mouse model of diet induced obesity. METHODS: C57BL/6 mice were fed a high fat
      diet (HFD: 45% kcal fat) or standard chow (CHOW: 12% kcal fat) for 20 weeks and
      some animals (HFD+DM or CHOW+DM) were also rendered diabetic by low dose
      streptozotocin for the final 5 weeks, to model type 2 diabetes. Serum assays
      included circulating insulin, triglyceride, ALT and AST, glucose, and
      ultrasensitive CRP and results of insulin tolerance tests. Intrahepatic lipid,
      triglyceride, macrophage infiltration, and fibrosis were determined. Fibrosis
      markers collagen-I, collagen-III, CTGF, TIMP-1, and FAP were assessed by qPCR and
      CTGF and collagen-I by immunostaining. RESULTS: HFD mice were obese, insulin
      resistant and hyperinsulinaemic, with NASH features of elevated intrahepatic
      lipid and macrophages, but without fibrosis. In contrast, the HFD+DM mice
      exhibited fibrosis in addition to these NASH features. By ANOVA, Sirius red
      staining at perisinusoidal, portal tract and central vein sites, collagen-I,
      collagen-III, FAP, and TIMP-1 transcripts and collagen-I and CTGF protein were
      each significantly increased in HFD+DM, compared with CHOW alone. In a further
      experiment, insulin treatment protected against fibrosis and CRP increases in
      HFD+DM, showing that diabetes, not streptozotocin, causes the fibrosis.
      CONCLUSIONS: This novel model indicates that diet-induced NASH fibrosis is
      exacerbated by diabetes and attenuated by insulin therapy.

PMID- 21184786
TI  - Deletion of steroid receptor coactivator-3 gene ameliorates hepatic steatosis.
AB  - BACKGROUND & AIMS: Excess dietary fat can cause hepatic steatosis, which can
      progress into severe liver disorders including steatohepatitis and cirrhosis.
      Steroid receptor coactivator-3 (SRC-3), a member of the p160 coactivator family,
      is reported as a key regulator of adipogenesis and energy homeostasis. We sought
      to determine the influence of SRC-3 on hepatic steatosis and the mechanism
      beneath. METHODS: The influence of siRNA-mediated SRC-3 silencing on hepatic
      lipid accumulation was assessed in HepG2 cells. The molecular mechanism of SRC-3
      regulation of hepatic lipid metabolism was also studied. Moreover, the effect of
      SRC-3 ablation on hepatic steatosis was examined in SRC-3 deficient mice.
      RESULTS: In this study, we report that SRC-3 ablation reduces palmitic acid
      induced lipid accumulation in HepG2 cells. Moreover, deletion of SRC-3
      ameliorates hepatic steatosis and inflammation response in mice fed a high fat
      diet (HFD). These metabolic improvements can presumably be explained by the
      reduction in chicken ovalbumin upstream promoter transcription factor II (COUP
      TFII) expression and the subsequent elevation in peroxisome proliferator
      activated receptor alpha (PPARalpha) level. At the molecular level, SRC-3
      interacts with retinoic receptor alpha (RARalpha) to activate COUP-TFII
      expression under all-trans retinoic acid (ARTA) treatment. CONCLUSIONS: These
      findings indicate a crucial role for SRC-3 in regulating hepatic lipid metabolism
      and provide the possible novel inner mechanisms.

PMID- 21184787
TI  - Augmentation of DHCR24 expression by hepatitis C virus infection facilitates
      viral replication in hepatocytes.
AB  - BACKGROUND & AIMS: We characterized the role of 24-dehydrocholesterol reductase
      (DHCR24) in hepatitis C virus infection (HCV). DHCR24 is a cholesterol
      biosynthetic enzyme and cholesterol is a major component of lipid rafts, which is
      reported to play an important role in HCV replication. Therefore, we examined the
      potential of DHCR24 as a target for novel HCV therapeutic agents. METHODS: We
      examined DHCR24 expression in human hepatocytes in both the livers of HCV
      infected patients and those of chimeric mice with human hepatocytes. We targeted
      DHCR24 with siRNA and U18666A which is an inhibitor of both DHCR24 and
      cholesterol synthesis. We measured the level of HCV replication in these HCV
      replicon cell lines and HCV infected cells. U18666A was administrated into
      chimeric mice with humanized liver, and anti-viral effects were assessed.
      RESULTS: Expression of DHCR24 was induced by HCV infection in human hepatocytes
      in vitro, and in human hepatocytes of chimeric mouse liver. Silencing of DHCR24
      by siRNA decreased HCV replication in replicon cell lines and HCV JFH-1 strain
      infected cells. Treatment with U18666A suppressed HCV replication in the replicon
      cell lines. Moreover, to evaluate the anti-viral effect of U18666A in vivo, we
      administrated U18666A with or without pegylated interferon to chimeric mice and
      observed an inhibitory effect of U18666A on HCV infection and a synergistic
      effect with interferon. CONCLUSIONS: DHCR24 is an essential host factor which
      augmented its expression by HCV infection, and plays a significant role in HCV
      replication. DHCR24 may serve as a novel anti-HCV drug target.

PMID- 21184788
TI  - Impact of artificial sunlight therapy on the progress of non-alcoholic fatty
      liver disease in rats.
AB  - BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is recognized as the most
      severe form of non-alcoholic fatty liver disease, with likely progression to
      liver cirrhosis and hepatocellular carcinoma. However, there is no unified
      standard for diagnosis and therapeutics. This study aimed to characterize lipid
      transfer/metabolic proteins as non-invasive diagnostic markers, and to evaluate
      the therapeutic effects of phototherapy on the progression of NASH in rats.
      METHODS: Lewis rats given a choline-deficient and iron-supplemented l-amino acid
      defined (CDAA) diet and Zucker fa/fa rats were used as a diet-induced and an
      obesity-related NASH models, respectively, with or without phototherapy. RESULTS:
      Serum apolipoprotein E and low molecular weight-adiponectin levels were gradually
      reduced and reached the lowest level at fatty liver/NASH stage both in CDAA diet
      induced NASH model and in genetically obese model. Total-adiponectin levels were
      dramatically elevated after NASH was established in CDAA diet-induced NASH model.
      Phototherapy ameliorated hepatocyte apoptosis, inflammation, fibrosis, and
      insulin/leptin resistance caused by CDAA diet with alteration of the levels of
      lipid transfer/metabolic proteins and elevation of the circulating active form of
      vitamin D(3). Vitamin D(3) supplementation ameliorated NASH progression in CDAA
      diet-induced NASH model. However, phototherapy failed to ameliorate the obesity
      and steatosis, suggesting that phototherapy may possess anti
      inflammatory/fibrotic activity rather than anti-obesity/steatotic activity.
      CONCLUSIONS: These results suggest that serum lipid transfer/metabolic proteins
      and vitamin D(3) status may be effective biomarkers for non-invasive diagnosis of
      NASH progression, and that phototherapy may be a good complementary therapy for
      NASH because of its regulation of lipid transfer/metabolic proteins and vitamin
      D(3).

PMID- 21184789
TI  - Regeneration of cartilage and bone by defined subsets of mesenchymal stromal
      cells--potential and pitfalls.
AB  - Mesenchymal stromal cells, also referred to as mesenchymal stem cells, can be
      obtained from various tissues. Today the main source for isolation of mesenchymal
      stromal cells in mammals is the bone marrow. Mesenchymal stromal cells play an
      important role in tissue formation and organogenesis during embryonic
      development. Moreover, they provide the cellular and humoral basis for many
      processes of tissue regeneration and wound healing in infancy, adolescence and
      adulthood as well. There is increasing evidence that mesenchymal stromal cells
      from bone marrow and other sources including term placenta or adipose tissue are
      not a homogenous cell population. Only a restricted number of appropriate stem
      cells markers have been explored so far. But routine preparations of mesenchymal
      stromal cells contain phenotypically and functionally distinct subsets of stromal
      cells. Knowledge on the phenotypical characteristics and the functional
      consequences of such subsets will not only extend our understanding of stem cell
      biology, but might allow to develop improved regimen for regenerative medicine
      and wound healing and novel protocols for tissue engineering as well. In this
      review we will discuss novel strategies for regenerative medicine by specific
      selection or separation of subsets of mesenchymal stromal cells in the context of
      osteogenesis and bone regeneration. Mesenchymal stromal cells, which express the
      specific cell adhesion molecule CD146, also known as MCAM or MUC18, are prone for
      bone repair. Other cell surface proteins may allow the selection of chondrogenic,
      myogenic, adipogenic or other pre-determined subsets of mesenchymal stromal cells
      for improved regenerative applications as well.

PMID- 21184790
TI  - Repeated glucoprivation delayed hyperphagic responses while activating
      neuropeptide Y neurons in rats.
AB  - It is well known that glucoprivation induces the release of counterregulatory
      hormones such as glucagon, and that the response is attenuated when the stimuli
      are repeated. Glucoprivation also activates orexigenic neurons and induces
      hyperphagic responses, although it remains unclear whether these responses are
      attenuated in repeated glucoprivation. In this study, we examined time course
      changes in feeding as well as activities of orexigenic neuropeptide Y (NPY)
      neurons in repeated glucoprivation in rats. Either 2-deoxy-d-glucose (2DG), which
      blocks glucose utilization, or isotonic saline (control) was injected
      subcutaneously to rats for 14 days, and food consumption for 1 and 2h after
      injection was monitored throughout the experiment. While 2DG injection induced
      robust feeding responses during the first 1h after injection, the response was
      gradually attenuated and the food consumption was significantly less on days 12
      14 compared to that on day 1. On the other hand, food consumption during 2h after
      2DG injection was not changed significantly for 14 days. The transcriptional
      activities of NPY neurons in the arcuate nucleus and C1/A1 region of the
      hindbrain, measured by intronic in situ hybridization, were significantly
      enhanced after repeated 2DG injection for 14 days, while the feeding responses to
      intracerebroventricular injection of NPY were significantly less in the 2DG
      repeated group compared to the saline-repeated group. It is thus demonstrated
      that repeated glucoprivation delayed hyperphagic responses while activating NPY
      neurons in rats. Our data also suggest that decreased feeding responses to NPY
      might be at least partially responsible for the delayed response.

PMID- 21184791
TI  - Venom peptides from solitary hunting wasps induce feeding disorder in
      lepidopteran larvae.
AB  - The cell lytic activity and toxicity against lepidopteran larvae of 13 venom
      peptides (4 OdVPs and 9 EpVPs) from two solitary hunting wasps, Orancistrocerus
      drewseni and Eumenes pomiformis, were examined with mastoparan as a reference
      peptide. Of the 13 peptides, 7 were predicted to have alpha-helical structures
      that exhibit the typical character of amphipathic alpha-helical antimicrobial
      peptides. The remaining peptides exhibited coil structures; among these, EpVP5
      possesses two Cys residues that form an internal disulfide bridge. All the
      helical peptides including mastoparan showed antimicrobial and insect cell lytic
      activities, whereas only two of them were hemolytic against human erythrocytes.
      The helical peptides induced a feeding disorder when injected into the vicinity
      of the head and thorax of Spodoptera exigua larvae, perhaps because their non
      specific neurotoxic or myotoxic action induced cell lysis. At low concentrations,
      however, these helical peptides increased cell permeability without inducing cell
      lysis. These findings suggest that the helical venom peptides may function as non
      specific neurotoxins or myotoxins and venom-spreading factors at low
      concentrations, as well as preservatives for long-term storage of the prey via
      antimicrobial, particularly antifungal, activities.

PMID- 21184793
TI  - Novel experimental models and paradigms for neuropsychiatric disorders:
      Editorial.

PMID- 21184794
TI  - Association study of PDE4B with panic disorder in the Japanese population.
AB  - BACKGROUND: Panic disorder (PD) is a severe and chronic psychiatric disorder with
      genetic components underlying in its etiology. The Phosphodiesterase 4B (PDE4B)
      gene has been reported to be associated with several psychiatric disorders.
      Several studies indicated that PDE4B may be involved in the regulation of anxiety
      and depression. Therefore, we investigate the association of PDE4B with PD in the
      Japanese population. METHODS: We genotyped 14 single nucleotide polymorphisms
      (SNPs) of PDE4B in 231 PD cases (85 males and 146 females) and 407 controls (162
      males and 245 females). Differences in the genotype, allele and haplotype
      frequencies between the two groups were compared. RESULTS: We found a significant
      association between PDE4B and PD in the haplotype analysis (haplotype C-T-T-A,
      permutation P=0.031, OR=1.81, 95% CI=1.30-2.51). Sex-specific analyses
      demonstrated that PDE4B was associated with PD in females in the allele/genotype
      and haplotype analyses (rs10454453, allele P=0.042, genotype P=0.0034; haplotype
      C-T-T-A, permutation P=0.028). CONCLUSION: Our results suggest that PDE4B may
      play a role in the pathophysiology of PD in the Japanese population. Replication
      studies using larger samples will be needed for more reliable conclusions.

PMID- 21184795
TI  - The effect of lovastatin on oxidative stress and antioxidant enzymes in hydrogen
      peroxide intoxicated rat.
AB  - Oxidative stress has been linked to the development of many diseases and hastens
      the progression of cardiovascular diseases. Since lovastatin is used worldwide as
      a cholesterol lowering drug, the present study was undertaken to evaluate the
      antioxidant property of lovastatin against H(2)O(2) induced oxidative stress in
      rats. Four study groups of rats of four animals each were treated with DMSO
      (control), H(2)O(2) (OS), lovastatin (L) and H(2)O(2) + lovastatin (OSL). On the
      15th day the animals were sacrificed, and the liver and heart tissues were
      analyzed for oxidative stress biomarkers and anti-oxidant enzymes. Results of the
      OSL-group showed a reduction in thiobarbituric acid reactive substances in liver
      (42.7%) and heart tissue (8%) compared with the control group. An increase was
      observed in the activity of the antioxidant enzymes, catalase (34.6% in liver and
      33.3% in heart) and glutathione peroxidase (50.5% in liver and 34.7% in heart). A
      commensurate increase in the activity of G6PDH was observed indicating an
      enhanced requirement of NADPH. The ratio GSH:GSSG in liver (1.05) and heart
      (0.84) was satisfactorily regulated compared to the control group (1.01 in liver
      and 0.93 in heart). These results suggest that lovastatin possesses antioxidant
      activity and reduces oxidative stress.

PMID- 21184792
TI  - Effects of fatty acid unsaturation numbers on membrane fluidity and alpha
      secretase-dependent amyloid precursor protein processing.
AB  - Fatty acids may integrate into cell membranes to change physical properties of
      cell membranes, and subsequently alter cell functions in an unsaturation number
      dependent manner. To address the roles of fatty acid unsaturation numbers in
      cellular pathways of Alzheimer's disease (AD), we systematically investigated the
      effects of fatty acids on cell membrane fluidity and alpha-secretase-cleaved
      soluble amyloid precursor protein (sAPP(alpha)) secretion in relation to
      unsaturation numbers using stearic acid (SA, 18:0), oleic acid (OA, 18:1),
      linoleic acid (LA, 18:2), alpha-linolenic acid (ALA, 18:3), arachidonic acid (AA,
      20:4), eicosapentaenoic acid (EPA, 20:5), and docosahexaenoic acid (DHA, 22:6).
      Treatments of differentiated human neuroblastoma (SH-SY5Y cells) with AA, EPA and
      DHA for 24h increased sAPP(alpha) secretion and membrane fluidity, whereas those
      treatments with SA, OA, LA and ALA did not. Treatments with AA and DHA did not
      alter the total expressions of amyloid precursor protein (APP) and alpha
      secretases in SH-SY5Y cells. These results suggested that not all unsaturated
      fatty acids but only those with 4 or more double bonds, such as AA, EPA and DHA,
      are able to increase membrane fluidity and lead to increase in sAPP(alpha)
      secretion. This study provides insights into dietary strategies for the
      prevention of AD.

PMID- 21184796
TI  - Neuroprotective effect of ginger on anti-oxidant enzymes in streptozotocin
      induced diabetic rats.
AB  - The aim of the present study was to investigate the effect of ginger on oxidative
      stress markers in the mitochondrial fractions of cerebral cortex (CC), cerebellum
      (CB), hippocampus (HC) and hypothalamus (HT) of diabetic rats. Diabetes
      exacerbates neuronal injury induced by hyperglycemia mediated oxidative damage. A
      marked decrease in anti-oxidant marker enzymes, superoxide dismutase (SOD),
      catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced
      glutathione (GSH) and increase in malondialdehyde (MDA) was observed in the
      diabetic rats. Decreased activities of anti-oxidant enzymes in diabetic rats were
      augmented on oral administration of ginger. Moreover, ginger administration
      depleted the MDA level, which was earlier increased in the diabetic rats. These
      results suggest that ginger exhibit a neuroprotective effect by accelerating
      brain anti-oxidant defense mechanisms and down regulating the MDA levels to the
      normal levels in the diabetic rats. Thus, ginger may be used as therapeutic agent
      in preventing complications in diabetic patients.

PMID- 21184797
TI  - Toxicological studies on a standardized extract of Solanum indicum ssp.
      distichum.
AB  - A standardized extract of the fruits of Solanum distichum has previously been
      shown to possess anti-hypertensive activity in rats (ED50 about 1 mg/kg). Earlier
      acute toxicity studies had shown that single doses up to 2g/kg orally or
      intraperitoneally failed to show any signs of morbidity. To study its potential
      long-term toxicity, rats of either sex were fed orally 1g/kg of the extract daily
      over a period of 4 weeks to 6 months. The extract did not affect food intake or
      rate of growth of the animals. Blood counts and other hematological parameters
      remained unaffected. Treatment for 4 weeks had no effect on plasma cholesterol or
      blood urea nitrogen in both sexes, but extended treatment to 6 months tended to
      lower both parameters. Plasma creatinine, liver enzymes and fasting blood sugar,
      plasma electrolytes, total protein and albumin were not altered. Gross necropsy
      showed a 20% increase in liver to body weight ratios after 6 months. None of the
      body organs tested showed any histopathological changes. Bearing in mind that the
      dose of the extract used in this study was several 100 times greater than its
      ED50, the present findings point to the wide safety margin of the extract.

PMID- 21184798
TI  - Decomposing unpleasantness: differential exogenous attention to disgusting and
      fearful stimuli.
AB  - Negative stimuli have consistently been shown to efficiently attract exogenous
      attention. Two different types of unpleasant stimuli, disgusting and fearful,
      sharing similar arousal and valence, are usually employed as a single category.
      However, since they diverge in several important aspects (biological
      functionality, associated feelings, and central and peripheral physiological
      correlates), it may be expected that their potential to capture attention
      differs. Event-related potentials and behavioral indices were recorded while
      participants were engaged in a digit categorization task in response to three
      types of irrelevant, distracting pictures: disgusting, fearful and neutral.
      Disgusting trials were associated with worse performance than fearful trials in
      the digit categorization task as revealed by reaction times and number of errors.
      Moreover, P2-associated cuneus activation and scalp anterior P2 amplitude were
      greater for disgusting than for fearful distracters. All these indices reveal
      that, under the experimental conditions employed in the present study, disgusting
      distracters are more efficient at attracting exogenous attention than are fearful
      distracters.

PMID- 21184799
TI  - Emotionally positive stimuli facilitate lexical decisions-an ERP study.
AB  - The influence of briefly presented positive and negative emotional pictures on
      lexical decisions on positive, negative and neutral words or pseudowords was
      investigated. Behavioural reactions were the fastest following all positive
      stimuli and most accurate for positive words. Stimulus-locked ERPs revealed
      enhanced early posterior and late parietal attention effects following positive
      pictures. A small neural affective priming effect was reflected by P3 modulation,
      indicating more attention allocation to affectively incongruent prime-target
      pairs. N400 was insensitive to emotion. Response-locked ERPs revealed an early
      fronto-central negativity from 480ms before reactions to positive words. It was
      generated in both fronto-central and extra-striate visual areas, demonstrating a
      contribution of perceptual and, notably, motor preparation processes. Thus, no
      behavioural and little neural evidence for congruency-driven affective priming
      with emotional pictures was found, but positive stimuli generally facilitated
      lexical decisions, not only enhancing perception, but also acting rapidly on
      response preparation and by-passing full semantic analysis.

PMID- 21184800
TI  - The polo-like kinase inhibitor BI 2536 exhibits potent activity against malignant
      plasma cells and represents a novel therapy in multiple myeloma.
AB  - OBJECTIVE: Polo-like kinase 1 (Plk1) is a regulator of the cell cycle that has
      been implicated in the pathology of many cancers. We have investigated whether
      this kinase plays a role in multiple myeloma (MM) using the Plk1 inhibitor BI
      2536. MATERIALS AND METHODS: We have used six MM cell lines and six patient
      derived samples to determine the effects of the Plk1 inhibitor, BI 2536, on cell
      viability, apoptosis, and cytokinesis. We have also examined the effect of the
      microenvironment on these parameters and the effects of BI 2536 in combination
      with other antimyeloma agents. RESULTS: We show that MM cell lines and patient
      samples express PLK1 and that cell death by apoptosis occurs when Plk1 is
      inhibited. Cells treated with BI 2536 accumulate in the G(2)/M phase of the cell
      cycle causing endoduplication. The effects of BI 2536 are not abrogated when
      cells are cultured on extracellular matrix components, in the presence of
      interleukin-6, or with bone marrow stromal cells. CONCLUSIONS: Plk1 inhibition
      leads to cell death in MM cell lines and patient myeloma samples. Our data
      suggest that inhibition of Plk1 may have potential use as a therapeutic strategy
      in multiple myeloma.

PMID- 21184801
TI  - Therapeutic benefits in thalassemic mice transplanted with long-term-cultured
      bone marrow cells.
AB  - OBJECTIVE: Autologous bone marrow (BM) cells with a faulty gene corrected by gene
      targeting could provide a powerful therapeutic option for patients with genetic
      blood diseases. Achieving this goal is hindered by the low abundance of
      therapeutically useful BM cells and the difficulty maintaining them in tissue
      culture long enough to complete gene targeting without differentiating. Our
      objective was to devise a simple long-term culture system, using unfractioned BM
      cells, that maintains and expands therapeutically useful cells for >=4 weeks.
      MATERIALS AND METHODS: From 2 to 60 million BM cells from wild-type (WT) mice or
      from mice carrying a truncated erythropoietin receptor transgene were plated with
      or without irradiated fetal-liver-derived AFT024 stromal cells in 25-cm(2)
      culture flasks. Four-week-cultured cells were analyzed and transplanted into
      sublethally irradiated thalassemic mice (1 million cells/mouse). RESULTS: After 4
      weeks, cultures with AFT024 cells had extensive "cobblestone" areas. Optimum
      expansion of Sca-1-positive cells was 5.5-fold with 20 * 10(6) WT cells/flask and
      27-fold with 2 * 10(6) truncated erythropoietin receptor transgene cells. More
      than 85% of thalassemic mice transplanted with either type of cells had almost
      complete reversal of their thalassemic phenotype for at least 6 months, including
      blood smear dysmorphology, reticulocytosis, high ferritin plasma levels, and
      hepatic/renal hemosiderosis. CONCLUSIONS: When plated at high cell densities on
      irradiated fetal-liver-derived stromal cells, BM cells from WT mice maintain
      their therapeutic potential for 4 weeks in culture, which is sufficient time for
      correction of a faulty gene by targeting.

PMID- 21184802
TI  - RANBP17 is localized to the XY body of spermatocytes and interacts with SPEM1 on
      the manchette of elongating spermatids.
AB  - We identified Ran-binding protein 17 (RANBP17) as one of the interacting partners
      of sperm maturation 1 (SPEM1) using yeast 2-hybrid screening and
      immunoprecipitation assays. Expression profiling analyses suggested that RANBP17
      was preferentially expressed in the testis. Immunofluorescent confocal microscopy
      revealed a dynamic localization pattern of RANBP17 during spermatogenesis. In
      primary spermatocytes RANBP17 was mainly localized to the XY body. In the
      subsequent spermiogenesis, RANBP17 was first observed in the nuclei of round
      spermatids (steps 1-7) and then confined to the manchette of elongating
      spermatids (steps 8-14) together with its interacting partner SPEM1. In the Spem1
      null testes, levels of RANBP17 were significantly elevated. As a member of a
      large protein family involved in the nucleocytoplasmic transport, RANBP17 may
      have a role in sex chromosome inactivation during the meiotic phase of
      spermatogenesis, and also in the intramanchette transport during spermiogenesis.
      Interactions between RANBP17 and SPEM1, for the first time, point to a potential
      function of SPEM1 in the RANBP17-mediated nucleocytoplasmic transport.

PMID- 21184804
TI  - Liquorice and glycyrrhetinic acid increase DHEA and deoxycorticosterone levels in
      vivo and in vitro by inhibiting adrenal SULT2A1 activity.
AB  - The mineralocorticoid effects of liquorice are mediated by the inhibitory effects
      of one of its active components glycyrrhetinic acid on 11beta-hydroxysteroid
      dehydrogenase type 2. However, liquorice is reputed to have many medicinal
      properties and also contains a number of other potentially biologically active
      compounds. Here we have investigated the wider effects of oral liquorice on
      steroidogenesis focussing particularly on possible inhibitory effects of
      glycyrrhetinic acid on adrenal sulfotransferase activity. Salivary steroids were
      profiled by ELISA in groups of normal male and female volunteers after consuming
      either liquorice-containing or non-liquorice-containing confectionary for one
      week. Cortisol and cortisone levels reflected expected inhibition of 11beta
      hydroxysteroid dehydrogenase type 2 by glycyrrhetinic acid. Salivary aldosterone
      was decreased but deoxycorticosterone, dehydroepiandrosterone and testosterone
      were increased. To assess whether glycyrrhetinic acid directly affected
      steroidogenesis, free and conjugated steroids were measured in incubates of
      adrenocortical H295 cells, firstly, in the presence or absence of forskolin and
      secondly, with radiolabeled deoxycorticosterone or dehydroepiandrosterone.
      Glycyrrhetinic acid inhibited cortisone and enhanced cortisol synthesis
      consistent with 11beta-hydroxysteroid dehydrogenase type 2 inhibition. Basal and
      forskolin-stimulated syntheses of deoxycorticosterone and dehydroepiandrosterone
      conjugates were also inhibited in a dose-dependent manner; glycyrrhetinic acid
      inhibited the conjugation of deoxycorticosterone and dehydroepiandrosterone with
      IC50 values of 7 MUM. Inhibition of deoxycorticosterone and
      dehydroepiandrosterone conjugation was apparent within 4 h of starting
      glycyrrhetinic acid treatment and was not associated with changes in the
      expression of SULT 2A1 mRNA. SULT2A1 encodes the enzyme sulfotransferase 2A1
      which is responsible for the sulfonation of deoxycorticosterone and
      dehydroepiandrosterone as well as pregnenolone and 17-hydroxypregnenolone in
      human adrenal glands. We suggest that the glycyrrhetinic acid constituent of
      liquorice increases circulating and thereby, salivary levels of unconjugated
      deoxycorticosterone and dehydroepiandrosterone by inhibiting their conjugation at
      source within the adrenal cortex. This effect may contribute to the
      mineralocorticoid actions of glycyrrhetinic acid and gives substance to claims
      that liquorice also has androgenic properties.

PMID- 21184803
TI  - Defining adrenarche in the rhesus macaque (Macaca mulatta), a non-human primate
      model for adrenal androgen secretion.
AB  - Adrenarche, defined as a prepubertal increase in adrenal androgen secretion
      resulting from zona reticularis (ZR) maturation, is thought to occur only in
      humans and some Great Apes. In the rhesus macaque, studies of circulating
      dehydroepiandrosterone (DHEA) or its sulpho-conjugate (DHEAS) have failed to
      demonstrate a prepubertal rise typical of human adrenarche, but available data
      are cross-sectional and include few neonatal or early infant samples. However, ZR
      maturation is complete in rhesus infants by 3 months of age based on
      morphological and biochemical analyses. Furthermore, preliminary longitudinal
      studies from birth through infancy of castrated males, and intact males and
      females, suggests for the first time that there is a transient, prepubertal
      elevation of adrenal androgen in rhesus macaques. Serum DHEAS concentration
      increased, peaking between 6 and 8 weeks of age in castrate males, and intact
      males and females, then declined. These longitudinal profiles add
      endocrinological support to the morphological and biochemical evidence that
      adrenarche occurs in a narrow developmental window in infant rhesus macaques.
      Adrenarche in any species should be defined only after careful longitudinal
      hormone analysis have been conducted in stages of development that are suggested
      by morphological and biochemical evidence of ZR maturation.

PMID- 21184805
TI  - Impaired neonatal survival of pro-opiomelanocortin null mutants.
AB  - Intercrosses of heterozygous pro-opiomelanocortin (POMC) mice result in
      homozygous null progeny at lower frequencies than expected. Genotyping offspring
      at pre-, peri-, and postnatal stages revealed that over half of homozygous null
      mutants die in the early postnatal stages. To investigate the reasons for this
      early postnatal lethality, we analyzed in detail different parameters in the
      initial hours after birth. POMC null mutants born to heterozygous dams presented
      at birth with corticosterone levels no different from wildtype littermates, were
      euglycemic, and had normal liver glycogen stores. However, already 30 min after
      birth corticosterone levels dropped by 80% and were undetectable thereafter,
      while corticosterone levels in wildtype animals increased during postnatal hours.
      Circulating adrenaline was almost below detection 1h after birth. Blood glucose
      levels fell sharply in all genotypes within 30 min after birth; however, wildtype
      and heterozygous pups overcame hypoglycemia within an hour, while mutant pups
      stayed hypoglycemic. The depletion of liver glycogen stores in mutant pups was
      significantly less efficient compared to their littermates in the hours after
      birth. POMC null mutant mice born to POMC null mutant dams completely lack
      corticosterone and die of the expected respiratory dysfunction. In contrast, POMC
      null mutant mice born to heterozygous dams do not die of respiratory problems,
      but rather due to hypoglycemia. Our studies confirm an essential involvement of
      POMC peptides and of adrenal glucocorticoids and catecholamines on glucose
      homeostasis critical for early postnatal survival.

PMID- 21184806
TI  - A negative allosteric modulator demonstrates biased antagonism of the follicle
      stimulating hormone receptor.
AB  - High quality gamete production in males and females requires the pituitary
      gonadotropin follicle stimulating hormone (FSH). In this report a novel chemical
      class of small molecule inhibitors of FSH receptor (FSHR) is described. ADX61623,
      a negative allosteric modulator (NAM), increased the affinity of interaction
      between (125)I-hFSH and human FSHR (hFSHR) five fold. This form of FSHR occupied
      simultaneously by FSH and ADX61623 was inactive for cAMP and progesterone
      production in primary cultures of rat granulosa cells. In contrast, ADX61623 did
      not block estrogen production. This demonstrates for the first time, biased
      antagonism at the FSHR. To determine if ADX61623 blocked FSH induction of
      follicle development in vivo, a bioassay to measure follicular development and
      oocyte production in immature female rats was validated. ADX61623 was not
      completely effective in blocking FSH induced follicular development in vivo at
      doses up to 100mg/kg as oocyte production and ovarian weight gain were only
      moderately reduced. These data illustrate that FSHR couples to multiple signaling
      pathways in vivo. Suppression of one pool of FSHR uncouples Galphas and cAMP
      production, and decreases progesterone production. Occupancy of another pool of
      FSHR sensitizes granulosa cells to FSH induced estradiol production. Therefore,
      ADX61623 is a useful tool to investigate further the mechanism of the FSHR
      signaling dichotomy. This may lead to a greater understanding of the signaling
      infrastructure which enables estrogen biosynthesis and may prove useful in
      treating estrogen dependent disease.

PMID- 21184807
TI  - Downregulation of GABAB receptors in the spinal cord dorsal horn in diabetic
      neuropathy.
AB  - Diabetic neuropathic pain is a common clinical problem and remains difficult to
      treat with classic analgesics. Spinal dorsal horn neurons are important in
      mediating nociceptive signaling, and the hyperactivity of these neurons is
      critical in diabetic neuropathy. In this study, we determined the GABA(B)
      receptor expression level in dorsal horn neurons in streptozotocin (STZ)-induced
      diabetes in rats by using reverse-transcription polymerase chain reaction (RT
      PCR) and western blot analyses. Mean blood glucose concentrations were
      significantly higher and the paw withdrawal threshold was significantly lower in
      STZ-treated rats than in saline-treated rats. Immunohistochemical staining showed
      that the GABA(B) receptor was extensively expressed in the spinal dorsal horn
      neurons. The GABA(B1) mRNA level decreased in a time-dependent manner in STZ
      treated rats compared with saline-treated controls. Furthermore, the protein
      expression level revealed by western blot analysis was lower in STZ-treated rats
      than in saline-treated rats. These data suggest that GABA(B) receptors are
      downregulated in the spinal dorsal horn in this model of STZ-induced diabetic
      neuropathic pain. The reduction of GABA(B) expression may contribute to the
      hyperactivity of spinal dorsal horn neurons and diabetic neuropathic pain.

PMID- 21184808
TI  - Whole body lexical decision.
AB  - When a person standing upright raises an arm on cue, muscles of the left and
      right sides of the body exhibit changes prior to and specific to the responding
      arm. We had standing participants perform a visual lexical decision task ("is
      this letter string a word?"), responding yes by raising one arm and no by raising
      the other arm. We recorded onset of the arm movement and onset of
      electromyographic activity in thigh, trunk, and shoulder muscles. We observed the
      expected responding arm specificity and found that the onset difference favoring
      word decisions was evident in similar magnitude at all measurement sites, with
      the difference at the levels of thigh, trunk and shoulder muscles available 225,
      189, and 120 ms, respectively, prior to its manifestation at the level of arm
      movement. We discuss including (a) whole body reaction time along with event
      related potentials in determining the decision-response, brain-body temporal
      relation and (b) response execution along with response initiation in
      investigating mental chronometry.

PMID- 21184809
TI  - Chronic stress impairs learning and hippocampal cell proliferation in senescence
      accelerated prone mice.
AB  - Chronic stress can induce cognitive impairment. It is unclear whether a higher
      susceptibility to chronic stress is associated with the progression of
      pathological brain aging. Senescence-accelerated prone mouse 8 (SAMP8) is a
      naturally occurring animal model of accelerated brain aging. Senescence
      accelerated resistant mouse 1 (SAMR1) is usually used as the normal control. In
      this study, we examined the effects of chronic restraint stress (CRS) on learning
      in the Y-maze, hippocampal cell proliferation, and the expression of brain
      derived neurotrophic factor (BDNF) in the hippocampus of 4-month-old SAMP8 and
      SAMR1. The results showed that exposure to CRS impaired learning and hippocampal
      cell proliferation in SAMP8 and SAMR1 but to a much greater extent in SAMP8.
      Furthermore, CRS significantly decreased the expression of BDNF protein and mRNA
      in the hippocampus of SAMP8 and SAMR1. These data indicated that SAMP8 is more
      sensitive to the deleterious effects of CRS on learning than SAMR1. A greater
      decrease in hippocampal cell proliferation caused by chronic stress may be part
      of the underlying mechanism for the more severe learning deficit observed in
      SAMP8. In addition, our findings suggested a role of BDNF in the stress-induced
      impairment of learning and hippocampal cell proliferation in both strains.

PMID- 21184810
TI  - Are serotonin 3A and 3B receptor genes associated with suicidal behavior in
      schizophrenia subjects?
AB  - Suicide is a major contributor to the morbidity and mortality of schizophrenia,
      accounting for approximately 10% of deaths in these patients. Genetic factors
      have been reported to modulate the risk for suicide, although the precise
      mechanism and magnitude of the genetic contribution are unknown. Further, suicide
      attempters present abnormalities in the serotonergic system. We evaluated whether
      genetic variants in the serotonin receptors HTR3A (rs897692, rs1150226,
      rs1176724, rs2276302, rs3737457, rs897687 and rs1176713) and HTR3B (rs3758987,
      rs10502180, rs11606194, rs17116121, rs1176744, rs17116138, rs2276307, rs3782025
      and rs1176761) were susceptibility components for suicidal behavior in 154
      Caucasians schizophrenia subjects (20.1% of suicide attempters). In a second
      step, we compared haplotype and gene-gene interaction approaches because both
      genes are located in the chromosome 11q23 approximately 28Kbp apart. We did not
      observe allelic or genotypic associations. Six haplotypes were nominally
      significant associated with suicide. Gene-gene interaction using Helix Tree
      software showed two nominally significant interactions reproduced by haplotype
      association. Likewise, haplotypes composed by the markers included in the best
      multidimensional reduction three-locus model were nominally significant. Our
      results suggest that HTR3A and HTR3B polymorphisms may not play a major role in
      the susceptibility for suicidal behavior in schizophrenia subjects. Moreover,
      gene-gene interaction and haplotype association may have consistent results for
      genes located in the same chromosome.

PMID- 21184811
TI  - Neuromagnetic activity in the somatosensory cortices of children with cerebral
      palsy.
AB  - Children with cerebral palsy (CP) have altered tactile, proprioceptive and
      kinesthetic awareness. These sensory impairments appear to be related to an
      aberrant organization of the somatosensory cortex. To date, the neuromagnetic
      responses of somatosensory cortices representing the foot have not been
      investigated in children with spastic diplegic CP. In this investigation, we used
      magnetoencephalography (MEG) to evaluate cortical differences in the earliest
      somatosensory responses elicited by foot stimulation in typically developing
      children and those with spastic diplegic CP who have a Gross Motor Function
      Classification Score of III-IV. All participants underwent unilateral tibial
      nerve stimulation of each foot as whole brain MEG data were acquired. Primary
      somatosensory cortical responses were modeled using an equivalent current dipole
      for each foot. The results presented in this study are the first to show that
      activation of the somatosensory cortices representing the foot in children with
      spastic diplegic CP is diminished, but not latent.

PMID- 21184812
TI  - Tuning the gain of somato-sympathetic reflexes by stimulation of the thoracic
      spine in humans.
AB  - In animals, somatic stimulation of the limbs can evoke sympathetic reflexes of
      supraspinal origin. In addition, spinal reflexes can be elicited by stimulation
      of somatic tissues of the trunk. However, limited evidence is available
      concerning the specific modulation of sympathetic reflexes by afferents from the
      thoracic spine. This has also been largely overlooked in healthy humans. The aim
      of the present study was to determine whether tonic noxious heat (NH) applied to
      the skin over T3-T5 could segmentally increase supraspinal sympathetic reflexes
      (skin conductance responses - SCRs) induced by phasic electrical stimulation of
      the sural nerve. In addition, the effect of spinal manipulation (SM) on SCR
      amplitude and SCR amplification by NH was investigated. During the control
      session, palmar and plantar SCR amplitude was stable, showing no significant
      modulation. During NH and SM, however, palmar SCR amplitude was respectively
      increased and decreased in comparison to baseline, leading to a robust difference
      in SCR amplitude between the 2 conditions (p<0.001). Moreover, these changes were
      also significantly and marginally different compared to the control session
      (p=0.041 and p=0.053, respectively). Interestingly, when applied immediately
      before NH, SM had a preventive effect on palmar SCR amplification induced by NH.
      In sharp contrast, changes in plantar SCRs were not significantly different
      between sessions (p=0.42). Altogether, these results indicate that somatic
      stimulation of the thoracic spine may modulate somato-sympathetic reflexes
      segmentally in conscious, healthy volunteers.

PMID- 21184813
TI  - Hippocampal synaptic metaplasticity requires the activation of NR2B-containing
      NMDA receptors.
AB  - The potential to exhibit synaptic plasticity itself is modulated by previous
      synaptic activity, which has been termed as metaplasticity. In this paper, we
      demonstrated that the activation of N-methyl-d-aspartate (NMDA) receptor 2B
      (NR2B) subunit in NNDA receptors was required for hippocampal metaplasticity at
      Schaffer collateral-commissural fiber-CA1 synapses. Brief 5 Hz priming
      stimulation did not cause long-term synaptic plasticity; however, it could result
      in the inhibition of subsequently evoked long-term potentiation (LTP). Meanwhile,
      the application of selective antagonists for NR2B subunit of NMDA receptors after
      delivering priming stimulation could block the metaplasticity. In contrast, LTP
      induction was not affected by NR2B antagonists in slices without pre-treatment of
      priming stimulation. These results indicated that the activation of NR2B
      containing NMDA receptors was required for metaplasticity.

PMID- 21184814
TI  - The study of postnatal and later development of the taste and olfactory systems
      using the human brain mapping approach: an update.
AB  - Gustatory and olfactory functions are already present at birth, although the full
      development of both systems takes place postnatally. The existence of early
      postnatal sensitive periods throughout the developmental course of sensory
      systems, including the taste and olfactory, has been well documented. The normal
      postnatal and later development of any sensory function parallels development of
      the central nervous system. This development is associated with development
      related plastic changes that ensure the increasing efficiency of neural
      communication that takes place throughout development and correlates with signal
      changes acquired by means of neuroimaging techniques. In this paper, we review
      papers published in the last 10 years that have reported on the investigation of
      age-related changes in brain activation patterns in response to gustatory and
      olfactory processing with two related aims. We aim to ascertain the way in which
      developmental plastic changes within the taste and olfactory systems have been
      reflected in signals obtained through neuroimaging techniques. Furthermore, we
      aim to identify sensitive periods of gustatory and olfactory development by
      conducting a systematic review of research on brain activation patterns of the
      taste and olfactory systems that have been measured through neuroimaging
      techniques in developing populations. The main contribution of the present review
      is the identification of the need to conduct further research on developmental
      brain mapping of the taste and olfactory systems in newborns, children and
      adolescents, and on the association between developmental plastic changes and
      imaging signals. In addition, further developmental research based on
      longitudinal designs is required.

PMID- 21184815
TI  - A behavioral analysis of altruism.
AB  - Altruistic acts have been defined, in economic terms, as "...costly acts that
      confer economic benefits on other individuals" (Fehr and Fischbacher, 2003). In
      multi-player, one-shot prisoner's dilemma games, a significant number of players
      behave altruistically; their behavior benefits each of the other players but is
      costly to them. We consider three potential explanations for such altruism. The
      first explanation, following a suggestion by the philosopher Derek Parfit,
      assumes that players devise a strategy to avoid being free-loaders-and that in
      the present case this strategy dictates cooperation. The second explanation says
      that cooperators reject the one-shot aspect of the game and behave so as to
      maximize reward over a series of choices extending beyond the present situation
      (even though reward is not maximized in the present case). This explanation
      assumes that people may learn to extend the boundaries of their selves socially
      (beyond their own skin) as well as temporally (beyond the present moment). We
      propose a learning mechanism for such behavior analogous to the biological,
      evolutionary mechanism of group selection. The third explanation assumes that
      people's altruism is based on a straightforward balancing of undiscounted costs
      to themselves against discounted benefits to others (social discounting). The
      three proposed explanations of altruism complement each other.

PMID- 21184816
TI  - Influence of preparation method on polynucleotide conformation and
      pharmacological activity of lipoplex.
AB  - Conformations of polyinosinic acid [poly(I)] and polycytidylic acid [poly(C)] in
      liposomes (lipoplex) were investigated by both circular dichroism (CD)
      spectroscopy and fluorescence resonance energy transfer (FRET) measurements, and
      compared with those in aqueous solution. The results indicate that poly(I) and
      poly(C) take double-stranded structure in aqueous solution at pH 6.5-7.5 in the
      presence of NaCl at higher concentration than 50mM. Although lipoplex was
      prepared without NaCl to avoid aggregation of lipoplex particles, poly(I) and
      poly(C) were double-stranded in pre-mixed poly(I)/poly(C) lipoplex (pre-mixed
      LIC), prepared by adding a mixed solution of poly(I) and poly(C) to the cationic
      liposomes. However, poly(I) and poly(C) did not take double-stranded structure in
      separately mixed LIC, prepared by separate addition of poly(I) solution and
      poly(C) solution to the cationic liposomes. The physicochemical properties
      (particle diameter and zeta potential) of pre-mixed LIC and separately mixed LIC
      were not different, but the anti-proliferative effect of pre-mixed LIC on human
      epidermoid carcinoma A431 cells was about eight times greater than that of
      separately mixed LIC. Our results indicate that polynucleotide conformation in
      lipoplex is markedly influenced by the preparation method, and the polynucleotide
      conformation in lipoplex has a substantial effect on pharmacological activity.

PMID- 21184818
TI  - The effects of age and interaural delay on detecting a change in interaural
      correlation: The role of temporal jitter.
AB  - Duration thresholds for detecting a change in interaural correlation (from 0 to
      1, or from 1 to 0) in the initial portion of a 1-second, broadband noise (0-10
      kHz) were determined for younger and older adults in a two-interval, two
      alternative forced choice paradigm as a function of the interaural delay between
      the noise bursts presented to each ear. When the interaural delay was 0 ms, older
      adults found it harder to detect a change in correlation from 0 to 1 than from 1
      to 0. For younger adults, however, this pattern was reversed. For interaural
      delays greater than 0 ms, both younger adults and older adults found it easier to
      detect a change in interaural correlation from 0 to 1 for short interaural delays
      (1 ms) with the reverse being true for longer interaural delays (5 ms). It is
      shown that this pattern of results is expected if temporal jitter (loss of neural
      synchrony in the auditory system) increases with age and with interaural delay.
      The implications of these results for age-related changes in stream segregation
      are discussed.

PMID- 21184817
TI  - On the classification of pathways in the auditory midbrain, thalamus, and cortex.
AB  - Auditory forebrain pathways exhibit several morphological and physiological
      properties that underlie their specific neurobiological roles in auditory
      processing. Anatomically, such projections can be distinguished by their terminal
      size, arborization patterns, and postsynaptic dendritic locations. These
      structural features correlate with several postsynaptic physiological properties,
      such as EPSP amplitude, short-term plasticity, and postsynaptic receptor types.
      Altogether, these synaptic properties segregate into two main classes that are
      associated with either primarily information-bearing (Class 1) or modulatory
      (Class 2) roles, and have been used to delineate the principle routes of
      information flow through the auditory midbrain, thalamus, and cortex. Moreover,
      these synaptic properties engender as yet unexplored issues regarding the
      neuronal processing of auditory information, such as the convergent integration
      and long-term plasticity of auditory forebrain inputs.

PMID- 21184820
TI  - Insamhodo-tang, a traditional Korean medicine, regulates mast cell-mediated
      allergic inflammation in vivo and in vitro.
AB  - AIM OF THE STUDY: Insamhodo-tang (IHT) has traditionally been used in Korea to
      treat a variety of diseases, including chronic cough, tuberculosis, and chronic
      bronchitis. However, the anti-allergic and anti-inflammatory effects of IHT and
      its molecular mechanisms have yet to be clearly elucidated. In this study, we
      attempted to evaluate the effects of IHT on mast cell-mediated allergy
      inflammation in vitro and in vivo. MATERIALS AND METHODS: We investigated to
      ascertain the pharmacological effects of IHT on both compound 48/80-induced and
      2,4-dinitrofluorobenzene (DNFB)-induced allergic reactions under in vivo
      conditions. Additionally, to find a possible explanation for the anti
      inflammatory mechanisms of IHT, we evaluated the regulatory effects of IHT on the
      level of inflammatory mediators in phorbol 12-myristate 13-acetate plus calcium
      ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). RESULTS: The
      finding of this study demonstrated that IHT reduced compound 48/80-induced
      systemic anaphylactic shock, DNFB-induced dermatitis, and ear swelling responses
      in mice. Additionally, IHT inhibited the production of interleukin (IL)-6, IL-8,
      and TNF-alpha, as well as the activation of nuclear factor-kappaB and caspase-1
      in PMACI-stimulated HMC-1. CONCLUSION: Collectively, the findings of this study
      provide us with a novel insight into the pharmacological actions of IHT as a
      potential molecule for use in the treatment of allergic inflammation diseases.

PMID- 21184819
TI  - Effect of Alnus japonica extract on a model of atopic dermatitis in NC/Nga mice.
AB  - AIM OF THE STUDY: The bark of Alnus species has long been used in traditional
      oriental medicine in the treatment of many pathological conditions, including
      fever, hemorrhage, diarrhea, alcoholism, various skin diseases (e.g. chronic
      herpes, eczema and prurigo), and inflammation. In order to assess the
      immunomodulatory efficacy of a novel herbal medicine in treating atopic
      dermatitis, we measured serum levels of several allergic and inflammatory
      biomarkers in NC/Nga mice before and after treatment with this experimental
      agent. MATERIALS AND METHODS: Gene and protein expression analyses of iNOS and
      COX-2 were quantified by real time PCR and Western blot analysis and serum levels
      of IL-4, -5 and -13 were also measured by ELISA, all of which were reduced after
      treatment with the experimental agent. Additionally, serum concentrations of IgE
      and blood eosinophil counts were reduced in treated mice. RESULTS: The topical
      application of leaf and bark extract from Alnus japonica suppressed the
      development of AD-like skin lesions. The percent of blood eosinophils was
      decreased after treatment with leaf and bark extract from Alnus japonica. The
      serum IgE and Th2-related cytokine levels were decreased after treatment with
      leaf and bark extract from Alnus japonica compared with those treated with base
      cream (vehicle treated AD group). The IL-4, IL-5 and IL-13 were lower than those
      of vehicle treated AD group. CONCLUSIONS: We contend that leaf and bark extract
      from Alnus japonica may prove useful in the treatment of atopic dermatitis and
      other allergic skin diseases, although more in-depth clinical studies are
      necessary before clinical implementation.

PMID- 21184821
TI  - Inhibition of 2,4-dinitrofluorobenzene-induced atopic dermatitis by topical
      application of the butanol extract of Cordyceps bassiana in NC/Nga mice.
AB  - ETHNOPHARMACOLOGICAL SIGNIFICANCE: The Cordyceps species are insect-borne
      mushrooms that have been ethnopharmacologically used for skin diseases such as
      eczema and dermatitis. AIM OF THE STUDY: In this study, we investigated the
      curative effects of the butanol fraction (CBBF) of Cordyceps bassiana on atopic
      dermatitis. MATERIALS AND METHODS: Dermatitis was induced by repeated application
      of 2,4-dinitrofluorobenzene (DNFB) in NC/Nga mice. After a topical application of
      CBBF on the skin lesions, the dermatitis score, epidermal thickness, mast cell
      number, and interleukin (IL)-4 and interferon (IFN)-gamma, as well as the levels
      of histamine and immunoglobulin E (IgE) in the serum, were measured. Moreover,
      effect of CBBF on histamine release was examined using RBL-2H3 under stimulation
      with 2,4-dinitrophenylated bovine serum albumin (DNP-BSA). RESULTS: CBBF
      inhibited atopic dermatitis symptoms and signs in the DNFB-treated NC/Nga mice.
      The suppressive activity of topically applied CBBF may be due to the dose
      dependent blockade of a series of immunopathological events, including the
      release of histamine, the production of IgE, and the secretion of IL-4 and IFN
      gamma. However, this extract did not directly suppress the degranulation process,
      assessed by measuring beta-hexosaminidase release. CONCLUSIONS: Our results
      suggest that CBBF can be applied as an effective herbal remedy to treat atopic
      dermatitis.

PMID- 21184822
TI  - A high content screening assay for identifying lysosomotropic compounds.
AB  - Lysosomes are acidic organelles that are essential for the degradation of old
      organelles and engulfed microbes. Furthermore, lysosomes play a key role in cell
      death. Lipophilic or amphiphilic compounds with a basic moiety can become
      protonated and trapped within lysosomes, causing lysosomal dysfunction.
      Therefore, high-throughput screens to detect lysosomotropism, the accumulation of
      compounds in lysosomes, are desirable. Hence, we developed a 96-well format, high
      content screening assay that measures lysosomotropism and cytotoxicity by
      quantitative image analysis. Forty drugs, including antidepressants,
      antipsychotics, antiarrhythmics and anticancer agents, were tested for their
      effects on lysosomotropism and cytotoxicity in H9c2 cells. The assay correctly
      identified drugs known to cause lysosomotropism and revealed novel information
      showing that the anticancer drugs, gefitinib, lapatinib, and dasatinib, caused
      lysosomotropism. Although structurally and pharmacologically diverse, drugs that
      were lysosomotropic shared certain physicochemical properties, possessing a
      ClogP>2 and a basic pKa between 6.5 and 11. In contrast, drugs which did not lie
      in this physicochemical property space were not lysosomotropic. The assay is a
      robust, rapid screen that can be used to identify lysosomotropic, as well as,
      cytotoxic compounds, and can be positioned within a screening paradigm to
      understand the role of lysosomotropism as a contributor to drug-induced toxicity.

PMID- 21184823
TI  - Choline acetyltransferase of the common type immunoreactivity in the rat brain
      following different heroin treatments: a pilot study.
AB  - Previous studies suggest that behavioral consequences of heroin treatment depend
      on the drug history of the animals and that cholinergic neurotransmission is
      involved in both behavioral and motor sensitization induced by heroin and other
      drugs of abuse. Immunohistochemistry, using a recently developed antiserum,
      specific for choline acetyl-transferase of the common type (cChAT), was applied
      to four different groups of rats, differing in drug regimens. Two groups of rats
      were submitted to the same schedule of heroin sensitization and then challenged
      for vehicle or heroin before sacrifice, obtaining two distinct groups, namely
      heroin-vehicle (HV) and heroin-heroin (HH). The same challenge was applied to
      another group of rats, previously submitted to a treatment with vehicle,
      obtaining other two groups, vehicle-vehicle (VV) and vehicle-heroin (VH),
      respectively. The number of cChAT-positive neurons is significantly increased
      (p<0.05) in the diagonal band nuclei (with a consequent increase of cChAT
      positive fibers in the dentate gyrus) and notably, even not significantly
      (p>0.05), increased in the nucleus accumbens core of heroin-sensitized rats (HV,
      HH). Instead, acute heroin treatment significantly increase (p<0.05) the number
      of cChAT-positive cells in the nucleus accumbens shell of both heroin-naive (VH)
      and heroin-sensitized (HH) rats. In heroin-sensitized rats (HV, HH), moreover,
      staining intensity of cChAT-positive fibers is significantly increased in the
      dorsal striatum, and basolateral amygdala (p<0.05). Unlikely, cChAT positive
      fibers in the central amygdala are significantly increased (p<0.05) by acute
      heroin treatments (VH, HH). The increase of cholinergic fibers in the dentate
      gyrus of the heroin sensitized rats (HV, HH) seems accompanied by a evident
      reduction in calretinin immunoreactive neurons in the same area. Our results, in
      a small group of animals, support the view that cholinergic mechanisms are
      intimately associated with the development of addictive phenotype. Furthermore,
      they suggest that cholinergic system is differentially engaged, following
      different heroin treatments.

PMID- 21184824
TI  - Calcitonin-like immunoreactivity in the subcommissural organ-Reissner's fiber
      complex of some freshwater and marine teleosts.
AB  - The subcommissural organ (SCO) is a highly specialised circumventricular
      ependymal organ covering and penetrating the posterior commissure. The secretory
      products of the SCO condense to form Reissner's fiber (RF). Because of its
      extensive secretory activity and the chemical properties of its secretion, the
      organ functions as similar to the neurosecretory cells. Teleosts comprised of
      more than 20,000 extant species that show great diversity in terms of the form,
      habit and habitat. Affinity of calcitonin antibodies for the SCO-RF complex was
      used as a histochemical tool to study the morphology of some freshwater and
      seawater teleosts and its potential correlate to their osmotic environment. While
      intense to moderate calcitonin-like immunoreactivity was seen in the cells of the
      SCO of majority of the freshwater species viz., common carp, catfish, eel and
      perch; the SCO of goldfish revealed limited immunoreactivity. Like the SCO, the
      RF in all species was also immunostained with antibodies against calcitonin. It
      appeared as a single, continuous fiber that ran from SCO into the third ventricle
      and extended through the aqueduct, fourth ventricle and central canal of the
      spinal cord. In contrast to that in the freshwater fishes, the SCO-RF complex in
      majority of the seawater fishes, showed no calcitonin-like immunoreactivity. The
      data presented in this study described the comparative histomorphology of the SCO
      RF complex and suggest a possibility that the calcitonin-like immunoreactivity in
      the SCO-RF complex might be a feature correlated to the osmotic environment of
      the fish.

PMID- 21184826
TI  - Biosynthesis and metabolism of steroids in molluscs.
AB  - Molluscs are the second most diverse animal group, they are ecologically
      important and they are considered excellent indicators of ecosystem health. Some
      species have been widely used in pollution biomonitoring programs; however, their
      endocrinology is still poorly known. Despite some studies reporting the presence
      of (vertebrate-type) steroids in molluscs, information regarding enzymatic
      pathways involved in steroid synthesis and further catabolism of those steroids
      is still fragmentary. Regarding steroidogenesis, a number of excellent studies
      were performed in the 70s using different radio-labelled steroid precursors and
      detecting the formation of different metabolites. But, since then a long gap of
      research exist until the late 90s when the 'endocrine disruption' issue raised
      the need of a better knowledge of mollusc (and invertebrate) endocrinology in
      order to assess alterations caused by pollutants. Here we summarize past and
      recent studies dealing with steroid biosynthesis and metabolism in different
      mollusc species. Most of these studies suggest the involvement of steroids in
      mollusc reproduction. However, the knowledge is still fragmentary and many
      questions remain to be answered.

PMID- 21184825
TI  - Neuroprotective mechanisms of minocycline against sphingomyelinase/ceramide
      toxicity: Roles of Bcl-2 and thioredoxin.
AB  - In this study, we determined whether minocycline may protect rat cortical
      cultures against neurotoxicity induced by sphingomyelinase/ceramide and explored
      the underlying mechanisms. We found that minocycline exerted strong
      neuroprotective effects against toxicity induced by bacterial sphingomyelinase
      and synthetic C2 ceramide. Minocycline enhanced the production of nitric oxide
      (NO) with resultant increases in cellular cGMP content. Consistently, minocycline
      dependent neuroprotection was abolished by the nitric oxide synthase inhibitor L
      N(G)-nitroarginine methyl ester (L-NAME) and the soluble guanylate cyclase (sGC)
      inhibitor 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ). Western blotting
      revealed that minocycline restored the expression levels of cGMP-dependent
      protein kinase (PKG)-1, antioxidative thioredoxin-1, and antiapoptotic Bcl-2 that
      were down-regulated by bacterial sphingomyelinase. Accordingly, the PKG inhibitor
      KT5823, the thioredoxin reductase inhibitor 1-chloro-2,4-dinitrobenzene (DNCB),
      and a Bcl-2 inhibitor significantly abolished the minocycline neuroprotection.
      The minocycline-dependent restoration of Bcl-2 was abolished by L-NAME, ODQ, and
      KT5823, but not by DNCB, suggesting the involvement of NO/sGC/PKG but not
      thioredoxin. Furthermore, minocycline-dependent recovery of thioredoxin-1 was PKG
      independent. Taken together, our results indicate that minocycline protects rat
      cortical neurons against bacterial sphingomyelinase/ceramide toxicity via an
      NO/cGMP/PKG pathway with induction of Bcl-2 and PKG-independent stimulation of
      thioredoxin-1.

PMID- 21184827
TI  - Extracting gene function from protein-protein interactions using Quantitative BAC
      InteraCtomics (QUBIC).
AB  - Large-scale proteomic screens are increasingly employed for placing genes into
      specific pathways. Therefore generic methods providing a physiological context
      for protein-protein interaction studies are of great interest. In recent years
      many protein-protein interactions have been determined by affinity purification
      followed by mass spectrometry (AP-MS). Among many different AP-MS approaches, the
      recently developed Quantitative BAC InteraCtomics (QUBIC) approach is
      particularly attractive as it uses tagged, full-length baits that are expressed
      under endogenous control. For QUBIC large cell line collections expressing tagged
      proteins from BAC transgenes or gene trap loci have been developed and are freely
      available. Here we describe detailed workflows on how to obtain specific protein
      binding partners with high confidence under physiological conditions. The methods
      are based on fast, streamlined and generic purification procedures followed by
      single run liquid chromatography-mass spectrometric analysis. Quantification is
      achieved either by the stable isotope labeling of amino acids in cell culture
      (SILAC) method or by a 'label-free' procedure. In either case data analysis is
      performed by using the freely available MaxQuant environment. The QUBIC approach
      enables biologists with access to high resolution mass spectrometry to perform
      small and large-scale protein interactome mappings.

PMID- 21184828
TI  - Constitutive and conditional RNAi transgenesis in mice.
AB  - Gene silencing by RNA interference (RNAi) has become a routine method for
      extracting function from the mammalian genome. Short hairpin (sh) RNAs expressed
      from stably integrated vectors mediate RNAi both in cultured cells and mice and
      present therefore a fast alternative to conventional knockout approaches. We
      describe three strategies to control gene silencing in mice by shRNA expression
      that can be applied to any transcript of interest. The strategies include
      germline and inducible cell type-specific knockdowns, which depending on the
      molecular switch applied can be either permanent (Cre/loxP) or reversible
      (tetO/tTA). For reliable expression the shRNAs of interest are knocked into a pre
      engineered Rosa26 docking site by recombinase mediated cassette exchange (RMCE).
      ES cells expressing the shRNA of interest can then be used to generate shRNA
      transgenic mice. The high efficiency of RMCE in ES cells enables the fast
      production of knockdown mice for in vivo functional analysis.

PMID- 21184829
TI  - Dysbindin C-A-T haplotype is associated with thicker medial orbitofrontal cortex
      in healthy population.
AB  - The dysbindin (dystrobrevin-binding protein 1) gene has been indicated as one of
      the most important schizophrenia susceptibility genes. Several genetic variations
      of this gene have been investigated by using an "intermediate phenotype" approach
      showing a particular detrimental effect on the prefrontal function in
      schizophrenic patients. However, the nature of dysbindin function within the
      brains of healthy individuals is poorly understood, in particular as concerns
      brain anatomy. We examine relationships between a previously implicated three
      marker C-A-T dysbindin haplotype and regional cortical thickness in a wide
      population genotyped for risk carriers (n=14) and non-risk carriers (n=93).
      Surface-based analysis of the cortical mantle showed that the dysbindin haplotype
      was associated with structural differences in the medial orbitofrontal cortex,
      where the risk carriers showed the highest cortical thickness values and the non
      risk carriers the lowest. Our study extends previous evidence found on
      schizophrenic patients to the healthy population, demonstrating the influence of
      dysbindin risk variants on the neuronal architecture of a specific brain region
      relevant to the neuropathology of schizophrenia.

PMID- 21184830
TI  - Patterns of cortical thickness and surface area in early Parkinson's disease.
AB  - Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder diagnosed on
      the basis of motor symptoms, but that also includes cognitive and visuo-spatial
      deficits. Though PD is known to initially affect subcortical regions, the cortex
      also exhibits neuronal loss in the course of the disease as post mortem studies
      have shown. So far, PD-related pattern of cortical damage remains unclear,
      because of disease-caused heterogeneity, and also in part because of
      methodological issues such as the limitations of Voxel Based Morphometry. Here
      corticometry was used, a technique that decouples local surface from thickness,
      to obtain a better picture of PD corticomorphometric patterns. We acquired MRI
      volumes for 33 healthy controls (HC) and 49 PD patients, extracted local cortical
      thickness and surface area and modeled both of them as a function of group and
      age for each participant. Cortical thickness averaged on the whole cortex did not
      differ between the two groups while mean surface area was significantly larger in
      the PD group. The bilateral parietal lobule, the right superior frontal gyrus,
      the left cingulate cortex and the left insular cortex exhibited larger local
      surface area in the PD group. The right precuneus exhibited cortical thinning
      associated with age in the PD group and not in the HC group. Furthermore,
      cortical thinning was observed in the PD group compared with the control group in
      the left medial supplementary motor area (SMA) and in the right dorsal pre-SMA.
      Finally, we found the left temporal pole thickness to correlate with disease
      duration, as well as the bilateral occipital cortex and Broca's area. These
      results suggest that PD etiology is associated with specific cortical
      alterations, which could account for cognitive deficits that arise as the disease
      evolves. Finally, our results observed in the occipital cortex as a function of
      disease duration may indicate the increase in PD-related visuo-spatial deficits,
      which can sometimes result in hallucinations later on in the disease. In the
      future, MRI-generated corticometry, combined with additional behavioral markers,
      may prove to be a useful diagnosis tool to characterize the evolution of motor
      and cognitive deficits in PD.

PMID- 21184831
TI  - Neuroanatomy in adolescents and young adults with 22q11 deletion syndrome:
      comparison to an IQ-matched group.
AB  - 22q11 deletion syndrome (22q11DS) is a common genetic condition associated with
      learning disability and high risk for psychiatric illness, in particular
      schizophrenia. Previous neuroimaging studies in children and adults with 22q11DS
      have uncovered a number of abnormalities, but have not differentiated between
      features relating to cognitive impairment and features relating to risk for
      schizophrenia. This structural MRI study compares adolescents with 22q11DS (n=14)
      to adolescents with idiopathic learning disability (n=13) and to typically
      developing controls (n=14). Voxel-based morphometry and region-of-interest
      volumetric analyses were employed to test specific hypotheses based on prior
      studies of 22q11DS. Features that differentiated 22q11DS participants from both
      matched-IQ and higher-IQ controls were total white matter volume reduction,
      occipito-parietal and anterior temporal grey matter reduction, frontal and insula
      grey matter enlargement, and corpus callosum enlargement. On the other hand,
      hippocampal volume and cerebellar hemisphere reductions differed between 22q11DS
      and higher-IQ controls only. The neuroanatomical substrates for cognitive
      impairment and psychiatric illness in 22q11DS are at least partially separable.
      Correlations between regional volumetric abnormalities and age suggest that
      exaggerated processes of normal adolescent brain maturation contribute to
      psychosis-risk in 22q11DS, consistent with previous findings in childhood-onset
      schizophrenia.

PMID- 21184832
TI  - COMT Val108/158Met genotype modulates human sensory gating.
AB  - BACKGROUND: The catechol-O-methyltransferase (COMT) Val(108/158)Met polymorphism
      of the dopamine system is essential for prefrontal cortex processing capacity and
      efficiency. In addition, dopaminergic neurotransmission is also associated with
      the sensory gating phenomenon protecting the cerebral cortex from information
      overload. It is however unclear if COMT genotype as a predictor of prefrontal
      efficiency modulates sensory gating on the level of the auditory cortex, i.e. the
      gating of the auditory evoked P50 and N100 components. METHODS: P50 and N100
      gating and COMT Val(108/158)Met genotype were determined in 282 healthy subjects
      of German descent carefully screened for psychiatric or neurological disorders.
      RESULTS: A significant effect of the COMT genotype was observed for N100 gating
      (F=4.510, df=2, p=0.012) but not for P50 gating (F=0.376, df=2, p=0.687).
      Contrast analysis showed that Met/Met individuals had poorer N100 gating compared
      to Val/Met (F=-12.931, p=0.003) and the Val/Val individuals (F=-11.056, p=0.057).
      CONCLUSION: The results indicate that a high prefrontal efficiency as suggested
      by the COMT Met/Met genotype is associated with to a poor sensory gating of the
      N100 component. This would fit in a model where a high prefrontal processing
      capacity allows a pronounced afferent input of sensory information from the
      auditory cortex as reflected by a poor sensory gating. The more pronounced
      prefrontal contribution to the N100 compared to the P50 component may explain the
      exclusive genotype association with the N100 sensory gating. This preliminary
      model should be replicated and validated in future investigations.

PMID- 21184833
TI  - New Zealand geckos (Diplodactylidae): Cryptic diversity in a post-Gondwanan
      lineage with trans-Tasman affinities.
AB  - We used a multi-gene approach to assess the phylogenetic relationships of New
      Zealand diplodactylid geckos to their Australian and New Caledonian relatives and
      to one another. Data from nuclear (RAG-1, PDC) and mitochondrial (ND2, 16S) genes
      from >180 specimens representing all 19 recognized New Zealand taxa and all but
      two of 20 putatively new species suggested by previous studies were analyzed
      using Maximum Parsimony, Maximum Likelihood and Bayesian inference. All analyses
      retrieved a monophyletic New Zealand clade, most closely related to the
      Australian Diplodactylidae exclusive of Pseudothecadactylus. Hoplodactylus is
      paraphyletic and composed of two morphological groups: a broad-toed clade,
      consisting of the island-restricted, largest extant species, Hoplodactylus
      duvaucelii, and the species-rich, wide-ranging Hoplodactylus maculatus clade; and
      a narrow-toed clade, comprising five monophyletic subgroups: Naultinus, the
      Hoplodactylus pacificus and Hoplodactylus granulatus clades, and the distinctive
      species Hoplodactylus rakiurae and Hoplodactylus stephensi. Each of these
      lineages is here recognized at the generic level. Our data support recognition of
      16 new species (36 total), and five new or resurrected genera (seven total). The
      New Zealand diplodactylid radiation split from its Australian relatives 40.2mya
      (95% highest posterior density estimate 28.9-53.5), after the opening of the
      Tasman Sea. Their distribution cannot, therefore, be regarded as derived as a
      result of Gondwanana vicariance. The age of the New Zealand crown group, 24.4mya
      (95% highest posterior density estimate 15.5-33.8), encompasses the period of the
      'Oligocene drowning' of New Zealand and is consistent with the hypothesis that
      New Zealand was not completely inundated during this period. Major lineages
      within New Zealand geckos diverged chiefly during the mid- to late Miocene,
      probably in association with a suite of geological and climatological factors
      that have characterized the region's complex history.

PMID- 21184834
TI  - Generation of a panel of monoclonal antibodies against atypical chemokine
      receptor CCX-CKR by DNA immunization.
AB  - INTRODUCTION: Chemokines are regulated by a family of 'atypical' chemokine
      receptors, D6, DARC and CCX-CKR, each of which efficiently internalizes its
      cognate chemokine ligands. Development of monoclonal antibodies (MAbs) that would
      recognize CCX-CKR on the cell surface will be helpful to identify primary CCX-CKR
      expressing cell types and analyze the fate of CCX-CKR after ligand binding to the
      receptor. METHODS: We generated IgG MAbs recognizing the cell-surface CCX-CKR by
      DNA immunization using a molecular adjuvant, and analyzed the epitope recognized
      by the MAbs. Then, the reactivities of the MAbs with CCX-CKR-transfected cells,
      and also hepatocytes and hepatic tumor lines were evaluated. Finally, we also
      tested the ligand-like activities of the MAbs, namely, induction of
      internalization of CCX-CKR by the MAbs. RESULTS: A panel of MAbs reacting with
      CCX-CKR expressed on the cell surface was prepared. The panel was a small one,
      consisting of only ten MAbs, but was rich in terms of diversity of the Ig
      isotypes and of the epitopes. Epitope analyses revealed that all the 10 MAbs
      recognized at least three different, although very close, peptide structures of
      the N-terminal domain. Three MAbs, namely, 2F11, 13E11 and 14F10, were selected
      to represent the panel. All of the MAbs were applicable for flow cytometry and
      immunoflurescent assays and immunoprecipitation. The reactivity of the 2F11 MAb
      was also confirmed by western blotting. Endogenous expression of CCX-CKR on human
      hepatocytes and hepatic tumor cell lines was demonstrated using the 13E11 MAb.
      Interestingly, binding of the 13E11 MAb with B300-19 cells expressing CCX-CKR
      resulted in induction of CCX-CKR internalization. DISCUSSION: This panel of MAbs
      may be expected to prove valuable for further study of the functions of this
      silent chemokine receptor, including those related to the homeostasis of lymphoid
      cells, and to the growth and metastasis of hepatic cancer.

PMID- 21184836
TI  - Human genetic studies on osteoarthritis from clinicians' viewpoints.

PMID- 21184835
TI  - Using ordered values of subregional cartilage thickness change increases
      sensitivity in detecting risk factors for osteoarthritis progression.
AB  - OBJECTIVE: To examine whether ordered values of (sub)regional femorotibial
      cartilage thickness change are superior to region-based approaches in detecting
      risk factors for cartilage loss in osteoarthritis (OA). METHODS: 58 women with
      knee OA had 3 Tesla MR images acquired at baseline and 24 months. Changes in
      cartilage thickness (?ThCtAB) were determined in eight medial femorotibial
      subregions. An ascending sort of individual ?ThCtAB measurements was done to
      create "ordered values". Risk factors for cartilage loss considered were: age,
      BMI, anatomical knee axis (AAA), minimal (medial) joint space width (mJSW), and
      percent of medial tibial plateau covered by the meniscus (percent cover). All
      change metrics were tested for association with the risk factors using Kendall's
      tau and relative sensitivity of multiple tests of subregions and ordered values
      were compared with single metrics of change from plate and compartment summaries
      and the first ordered value. RESULTS: The associations between subregion ?ThCtAB
      and AAA (P=0.0002), mJSW (P=0.016), and age (P=0.011) were significant, but only
      AAA (at alpha=0.05) and age (at alpha=0.1) remained significant after adjusting
      for multiple subregions. In contrast, cMFTC had P-values<0.05 for AAA (P=0.0001),
      mJSW (P=0.016), and meniscus subluxation (0.04). The first ordered value had
      significant associations with AAA (P=0.0004), mJSW (P=0.003), meniscus
      subluxation (P=0.02) and percent cover (P=0.031) all of which were significant at
      alpha=0.05 after adjusting for tests on multiple risk factors. CONCLUSION:
      Ordered values of ?ThCtAB were more sensitive in detecting risk factors of
      cartilage loss than subregional ?ThCtAB. Sensitivity was further enhanced by
      considering the minimum ordered value as a single test, thus not requiring
      adjustment for multiple tests. Using ordered values there was a significant
      association between ?ThCtAB and baseline AAA, mJSW, meniscus subluxation and
      meniscus percent cover. This study provides an important step in validating
      ordered values of cartilage change.

PMID- 21184837
TI  - Evaluation of unipodal stance in knee osteoarthritis patients using knee
      accelerations and center of pressure.
AB  - OBJECTIVE: This study aims to compare knee joint instability and postural
      impairments during the performance of a unipodal stance task between patients
      having knee osteoarthritis (OA) and healthy elderly subjects using knee
      accelerations and center of pressure (COP) measurements. MATERIALS AND METHODS:
      Twenty patients with medial knee OA and nine healthy individuals participated in
      this study. Three-dimensional (3D) knee joint accelerations and COP were measured
      during unipodal stance. The range and the root mean square (RMS) were extracted
      from medial lateral (ML) and anterior-posterior (AP) knee accelerations, whereas
      sway area, velocity, and ML and AP ranges were measured from the COP. The average
      parameters of three trials for each subject were compared between groups.
      RESULTS: Results show that knee OA patients exhibited a significantly higher
      range of knee acceleration in both ML (0.22+/-0.08 g vs 0.15+/-0.05 g) and AP
      (0.17+/-0.06 g vs 0.06+/-0.01 g) directions and a lower COP velocity (136.6+/
      22.3 mm/s vs 157.6+/-18.4 mm/s) than did the healthy age-matched group.
      Significant correlations between the COP and knee acceleration parameters were
      also obtained. CONCLUSIONS: This study confirmed that patients with knee OA
      displayed greater body sway than did able-bodied subjects. Moreover, using an
      accelerometric-based method, this study highlighted the higher knee joint
      instability in the frontal and sagittal planes in knee OA patients compared with
      able-bodied subjects during a unipodal standing task.

PMID- 21184838
TI  - Bacteraemia caused by Leptotrichia trevisanii in a neutropenic patient.
AB  - We describe an episode of Leptotrichia trevisanii bacteraemia in a neutropenic
      hemato-oncology patient receiving chemotherapy for Refractory Anemia with Excess
      Blasts-2 (RAEB-2). Although Leptotrichia spp. colonize the oral cavity and
      genitourinary tract, serious episodes of bacteraemia might occur in
      immunocompromised patients, particularly in those with severe neutropenia.
      Therefore, microbiologists should consider the possibility of Leptotrichia spp.
      septicemia in patients with blood cultures positive for gram negative bacilli,
      when routine microbiology tests fail to reveal a correct identification of the
      organism.

PMID- 21184839
TI  - Development of Prevotella nigrescens-specific PCR primers based on the nucleotide
      sequence of a Pn23 DNA probe.
AB  - A previous study reported the cloning of a putative Prevotella nigrescens
      specific DNA probe, Pn23, using random shotgun method. The present study
      evaluated the species-specificity of Pn23 for P. nigrescens using the clinical
      strains of Prevotella intermedia and P. nigrescens to develop P. nigrescens
      specific polymerase chain reaction (PCR) primers. Southern blot analysis showed
      that the DNA probe, Pn23, detected only the genomic DNA of P. nigrescens strains.
      PCR showed that the two sets of PCR primers, Pn23-F1/Pn23-R1 and Pn23-F2/Pn23-R2,
      had species-specificity for P. nigrescens. Interestingly, the two sets of PCR
      primers, Pn23-F6/Pn23-R6 and Pn23-F7/Pn23-R7, had strain-specificity for P.
      nigrescens ATCC 33563. The detection limits of the four primer sets were 40 or 4
      pg of the purified genomic DNA of P. nigrescens ATCC 33563. These results suggest
      that the DNA probe, Pn23, and the two sets of PCR primers, Pn23-F1/Pn23-R1 and
      Pn23-F2/Pn23-R2, can be useful for the detection of P. nigrescens in the
      molecular epidemiological studies of oral infectious diseases.

PMID- 21184840
TI  - Functional analysis of the fungal/plant class chitinase family in Aspergillus
      fumigatus.
AB  - A quintuple mutant was constructed to delete the entire family of the
      fungal/plant (class III) chitinases of Aspergillus fumigatus. Only a limited
      reduction in the total chitinolytic activity was seen for the different chitinase
      mutants including the quintuple mutant. In spite of this reduction in
      chitinolytic activity, no growth or germination defects were observed in these
      chitinase mutants. This result demonstrated that the fungal/plant chitinases do
      not have an essential role in the morphogenesis of A. fumigatus. A slight
      diminution of the growth during autolysis was seen for the quintuple mutant
      suggesting that class III chitinases may play only a nutritional role during this
      phase of the cycle, retarding fungal death.

PMID- 21184841
TI  - Mechanisms of carbacholine and GABA action on resting membrane potential and
      Na+/K+-ATPase of Lumbricus terrestris body wall muscles.
AB  - This work was aimed to identify the action of several ion channel and pump
      inhibitors as well as nicotinic, GABAergic, purinergic and serotoninergic drugs
      on the resting membrane potential (RMP) and assess the role of cholinergic and
      GABAergic sensitivity in earthworm muscle electrogenesis. The nicotinic agonists
      acetylcholine (ACh), carbacholine (CCh) and nicotine depolarize the RMP at
      concentrations of 5 MUM and higher. The nicotinic antagonists (+)tubocurarine,
      alpha-bungarotoxin, muscarinic antagonists atropine and hexamethonium do not
      remove or prevent the CCh-induced depolarization. Verapamil, tetrodotoxin,
      removal of Cl(-) and Ca(2+) from the solution also cannot prevent the
      depolarization by CCh. In a Na(+)-free medium, however, CCh lost this
      depolarization ability and this indicates that the drug opens the sodium
      permeable pathway. Serotonin, glutamate, glycine, adenosine triphosphate (ATP)
      and cis-4-aminocrotonic acid (GABA(C) receptor antagonist) had no effect on the
      RMP. On the other hand, isoguvacin, gamma-aminobutyric acid (GABA) and baclofen
      (GABA(B) receptor agonist) hyperpolarized the RMP. Ouabain, bicucullin (GABA(A)
      antagonist) and phaclofen (GABA(B) antagonist), as well as the removal of Cl(-),
      suppressed the effect of GABA and baclofen. CCh did not enhance the
      depolarization generated by ouabain but, on the other hand, hindered the
      hyperpolarizing activity of baclofen both in the absence and presence of atropine
      and (+)tubocurarine. The long-term application of CCh depolarizes the RMP
      primarily by inhibiting the Na(+)/K(+)-ATPase. The muscle membrane also contains
      A and B type GABA binding sites, the activation of which increases the RMP at the
      expense of increasing the action of ouabain- and Cl(-) -sensitive electrogenic
      pumps.

PMID- 21184842
TI  - Metabolic and physiological responses in tissues of the long-lived bivalve
      Arctica islandica to oxygen deficiency.
AB  - In Arctica islandica, a long lifespan is associated with low metabolic activity,
      and with a pronounced tolerance to low environmental oxygen. In order to study
      metabolic and physiological responses to low oxygen conditions vs. no oxygen in
      mantle, gill, adductor muscle and hemocytes of the ocean quahog, specimens from
      the German Bight were maintained for 3.5 days under normoxia (21 kPa=controls),
      hypoxia (2 kPa) or anoxia (0 kPa). Tissue levels of anaerobic metabolites
      octopine, lactate and succinate as well as specific activities of octopine
      dehydrogenase (ODH) and lactate dehydrogenase (LDH) were unaffected by hypoxic
      incubation, suggesting that the metabolism of A. islandica remains fully aerobic
      down to environmental oxygen levels of 2 kPa. PO(2)-dependent respiration rates
      of isolated gills indicated the onset of metabolic rate depression (MRD) below 5
      kPa in A. islandica, while anaerobiosis was switched on in bivalve tissues only
      at anoxia. Tissue-specific levels of glutathione (GSH), a scavenger of reactive
      oxygen species (ROS), indicate no anticipatory antioxidant response takes place
      under experimental hypoxia and anoxia exposure. Highest specific ODH activity and
      a mean ODH/LDH ratio of 95 in the adductor muscle contrasted with maximal
      specific LDH activity and a mean ODH/LDH ratio of 0.3 in hemocytes. These
      differences in anaerobic enzyme activity patterns indicate that LDH and ODH play
      specific roles in different tissues of A. islandica which are likely to economize
      metabolism during anoxia and reoxygenation.

PMID- 21184844
TI  - Heterogeneous sphingosine-1-phosphate lyase gene expression and its regulatory
      mechanism in human lung cancer cell lines.
AB  - The role of sphingolipid metabolic pathway has been recognized in determining
      cellular fate. Although sphingolipid degradation has been extensively studied,
      gene expression of human sphingosine 1-phosphate lyase (SPL) catalyzing
      sphingosine 1-phosphate (S1P) remains to be determined. Among 5 human lung cancer
      cell lines examined, SPL protein levels paralleled the respective mRNA and enzyme
      activities. Between H1155 and H1299 cells used for further experiments, higher
      cellular S1P was observed in H1155 with higher SPL activity compared with H1299
      with low SPL activity. GATA-4 has been reported to affect SPL transcription in
      Dictyostelium discoideum. GATA-4 was observed in H1155 but not in other cell
      lines. Overexpression of GATA-4 in H1299 increased SPL expression. However,
      promoter analysis of human SPL revealed that the most important region was
      located between -136bp and -88bp from the first exon, where 2 Sp1 sites exist but
      no GATA site. DNA pull-down assay of H1155 showed increased DNA binding of Sp1
      and GATA-4 within this promoter region compared with H1299. Electrophoresis
      mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP) assay, reporter
      assay using mutated binding motif, and mithramycin A, a specific Sp1 inhibitor,
      suggest the major role of Sp1 in SPL transcription and no direct binding of GATA
      4 with this 5' promoter region. The collaborative role of GATA-4 was proved by
      showing coimmunoprecipitation of Sp1 and GATA-4 using GST-Sp1 and overexpressed
      GATA-4. Thus, high SPL transcription of H1155 cells was regulated by Sp1 and GATA
      4/Sp1 complex formation, both of which bind to Sp1 sites of the 5'-SPL promoter.

PMID- 21184843
TI  - Valproate uncompetitively inhibits arachidonic acid acylation by rat acyl-CoA
      synthetase 4: relevance to valproate's efficacy against bipolar disorder.
AB  - BACKGROUND: The ability of chronic valproate (VPA) to reduce arachidonic acid
      (AA) turnover in brain phospholipids of unanesthetized rats has been ascribed to
      its inhibition of acyl-CoA synthetase (Acsl)-mediated activation of AA to AA-CoA.
      Our aim was to identify a rat Acsl isoenzyme that could be inhibited by VPA in
      vitro. METHODS: Rat Acsl3-, Acsl6v1- and Acsl6v2-, and Acsl4-flag proteins were
      expressed in E. coli, and the ability of VPA to inhibit their activation of long
      chain fatty acids to acyl-CoA was estimated using Michaelis-Menten kinetics.
      RESULTS: VPA uncompetitively inhibited Acsl4-mediated conversion of AA and of
      docosahexaenoic (DHA) but not of palmitic acid to acyl-CoA, but did not affect AA
      conversion by Acsl3, Acsl6v1 or Acsl6v2. Acsl4-mediated conversion of AA to AA
      CoA showed substrate inhibition and had a 10-times higher catalytic efficiency
      than did conversion of DHA to DHA-CoA. Butyrate, octanoate, or lithium did not
      inhibit AA activation by Acsl4. CONCLUSIONS: VPA's ability to inhibit Acsl4
      activation of AA and of DHA to their respective acyl-CoAs, when related to the
      higher catalytic efficiency of AA than DHA conversion, may account for VPA's
      selective reduction of AA turnover in rat brain phospholipids, and contribute to
      VPA's efficacy against bipolar disorder.

PMID- 21184845
TI  - Contribution of late sodium current (I(Na-L)) to rate adaptation of ventricular
      repolarization and reverse use-dependence of QT-prolonging agents.
AB  - BACKGROUND: Abnormal rate adaptation of ventricular repolarization is
      arrhythmogenic. There is controversy on the underlying ionic mechanisms for rate
      dependent change in repolarization. OBJECTIVE: The purpose of this study was to
      examine the role of the late sodium current (I(Na-L)) in normal rate-dependence
      of ventricular repolarization and reverse use-dependence of QT-prolonging agents.
      METHODS: The effects of I(Na-L) blockade, I(Na-L) enhancement, I(Kr) blockade,
      and changes in extracellular potassium concentration ([K(+)](o)) on rate
      adaptation of the QT interval and action potential duration (APD) were examined
      in isolated rabbit ventricular wedges and single myocytes. Rate dependence of
      I(Na-L), delayed rectifier potassium current (I(K)), and L-type calcium current
      (I(Ca)) was determined using a whole-cell, voltage clamp technique. RESULTS: At
      control, APD exhibited rate-dependent changes in the multicellular preparations
      as well as in the isolated single ventricular myocytes when [K(+)](o) remained
      constant. The rate dependence of APD was significantly enhanced by reduction of
      [K(+)](o) from 4 to 1 mM or by I(Na-L) enhancement but was markedly blunted by
      the selective sodium channel blocker tetrodotoxin. The I(Kr) blocker dofetilide
      (3 nM) amplified the QT to basic cycle length slope (71.2 +/- 13.1 ms/s vs 35.1
      +/- 8.8 ms/s in control, n = 4, P <.05). This reverse use-dependence was
      abolished by tetrodotoxin at 5 MUM (11.4 +/- 4.3 ms/s, n = 4, P <.01). There were
      no significant differences in I(Ca) or I(K) over the range of basic cycle lengths
      from 2,000 to 500 ms. However, I(Na-L) exhibited a significant rate-dependent
      reduction. CONCLUSION: I(Na-L) is sensitive to rate change due to its slow
      inactivation and recovery kinetics and plays a central role in the rate
      dependence of APD/QT and in the reverse use-dependence of select APD/QT
      prolonging agents.

PMID- 21184846
TI  - Occult hepatitis C virus infection and associated predictive factors: the
      Pakistan experience.
AB  - The aim of the present study was to determine the presence of HCV RNA in the
      liver biopsies of patients with abnormal liver tests but without detectable serum
      HCV RNA and anti-HCV antibodies in sera. Liver biopsies and whole blood of total
      31 patients who were negative for anti-HCV antibodies with elevated liver
      function tests were received at Division of Molecular Diagnostics, University of
      the Punjab Pakistan from January 2002 to June 2009 for the detection of HCV RNA.
      HCV RNA status of the subjects was tested by reverse-transcription PCR and
      quantified using SmartCycler II real-time PCR. HCV genotyping was carried out in
      HCV RNA positive samples using molecular genotyping method. HCV RNA was found in
      liver-biopsy specimens from 23 (74.2%) of the total 31 patients negative for anti
      HCV antibodies and undetectable serum HCV RNA. HCV RNA of both negative and
      positive polarity was found in the livers of 8 (25.8%) patients. Genotyping
      analysis showed that 65% patients were infected with HCV 3a, 17% with 3b, 13%
      with 1a and 4% patients were found with untypable genotype. In a multivariate
      logistic regression model, patients having previous history surgeries, male sex
      and age above 30 years were significantly associated with the presence of occult
      HCV infection (p<0.05). In conclusion, patients with elevated liver enzymes and
      negative HCV antibodies and negative serum RNA may have occult HCV infection and
      its chance increases with previous history of surgeries, in male sex and above 30
      years of age.

PMID- 21184847
TI  - Livedoid vasculopathy as a coagulation disorder.
AB  - Livedoid vasculopathy is an occlusive cutaneous disease of the dermal vessels
      with pauci-inflammatory or non-inflammatory histopathology findings. It is
      characterized by the presence of macules or papules, erythemato-purpuric lesions
      located on the legs, especially on the ankles and feet, which produce ulcerations
      that are intensely painful and originate ivory atrophic scars called "atrophie
      blanche". In this review article, studies on LV from the literature are analyzed,
      and their etiopathogenic associations, particularly those related to the
      thrombophilic states, as well as the pathologic findings and therapeutic
      approaches applied in the difficult clinical management of these cases, are
      evaluated.

PMID- 21184848
TI  - Protein crystal microspectrophotometry.
AB  - Single crystal microspectrophotometry has emerged as a valuable technique for
      monitoring molecular events that take place within protein crystals, thus tightly
      coupling structure to function. Absorption and fluorescence spectra, ligand
      binding affinities and kinetic constants can be determined, allowing i) the
      definition of the experimental conditions for X-ray crystallography experiments
      and their interpretation, ii) the assessment of whether crystal lattice forces
      have altered conformational equilibria, iii) the comparison with data obtained in
      solution. Microspectrophotometric measurements using oriented crystals and
      linearly polarized light are carried out usually off-line with respect to X-ray
      data collection and are aimed at an in- depth characterization of protein
      function in the crystal, leading to robust structure-function relationships. The
      power of this approach is highlighted by reporting a few case studies, including
      hemoglobins, pyridoxal 5'-phosphate-dependent enzymes and acetylcholinesterases.
      This article is part of a Special Issue entitled: Protein Structure and Function
      in the Crystalline State.

PMID- 21184849
TI  - Is entire nerve root decompression necessary for hemifacial spasm?
AB  - OBJECTIVE: The root exit zone (REZ) of the seventh cranial nerve has been the
      target of microvascular decompression surgery (MVD) while searching the
      neurovascular conflict for treatment of hemifacial spasm for long time. Recently,
      increasing cases regarding the offending vessel beyond the REZ have been
      reported. To verify whether a thorough dissection of the nerve may give rise to a
      better postoperative result without enhancing complications, we conducted a
      parallel investigation. PATIENTS AND METHODS: 112 Connective entire-nerve-exposed
      MVDs were performed and compared to 186 REZ-exposed MVDs performed by the same
      group of surgeons in 2009. The surgical findings, postoperative outcomes and
      complications as well as microscopic operating time were examined. RESULTS:
      Immediately after the surgery, the outcomes were excellent in 98.2%, good in 1.8%
      and poor in 0% in the entire-nerve-exposed group, compared to excellent in 92.5%,
      good in 1.6% and poor in 5.9% in the REZ-exposed group. The difference of
      outcomes between the two groups were statistically significant (chi(2)=4.6845,
      P=0.0304), but not the complications and microscopic operating time. Nine of the
      11 poor-outcome patients from the REZ-exposed group were then reoperated on
      within a few days, and their symptoms disappeared in eight patients. The main
      reason for the failed surgeries was that the offending vessels beyond REZ were
      missed. CONCLUSIONS: These findings suggested that the entire-root-decompression
      technique is recommended while performing MVDs in patients with hemifacial spasm.

PMID- 21184850
TI  - Developments for a growing Japanese patient population: facilitating new
      technologies for future health care.
AB  - Lung cancer, COPD and cardiovascular diseases are highlighted as some of the most
      common disease that cause mortality, and for that reason are the most active
      areas for drug development. This perspective paper overviews the urgent need to
      develop a health care system for a rapidly growing patient population in Japan,
      including forthcoming demands on clinical care, expecting outcomes, and
      economics. There is an increasing requirement to build on the strengths of the
      current health care system, thereby delivering urgent solutions for the future.
      There is also a declaration from the Ministry of Health, Labour and Welfare
      (MHLW), to develop new biomarker diagnostics, which is intended for patient
      stratification, aiding in diagnostic phenotype selection for responders to drug
      treatment of Japanese patients. This perspective was written by the panel in
      order to introduce novel technologies and diagnostic capabilities with successful
      implementation. The next generation of personalized drugs for targeted and
      stratified patient treatment will soon be available in major disease areas such
      as, lifestyle-related cancers, especially lung cancers with the highest mortality
      including a predisposing disorder chronic obstructive pulmonary disease,
      cardiovascular disease, and other diseases. Mass spectrometric technologies can
      provide the "phenotypic fingerprint" required for the concept of Personalized
      Medicine. Mass spectrometry-driven target biomarker diagnoses in combination with
      high resolution computed tomography can provide a critical pathway initiative
      facilitated by a fully integrated e-Health infrastructure system. We strongly
      recommend integrating validated biomarkers based on clinical proteomics, medical
      imaging with clinical care supported by e-Health model to support personalized
      treatment paradigms to reduce mortality and healthcare costs of chronic and co
      morbid diseases in the elderly population of Japan.

PMID- 21184851
TI  - N(alpha)-Acetylation of yeast ribosomal proteins and its effect on protein
      synthesis.
AB  - N(alpha)-Acetyltransferases (NATs) cause the N(alpha)-acetylation of the majority
      of eukaryotic proteins during their translation, although the functions of this
      modification have been largely unexplored. In yeast (Saccharomyces cerevisiae),
      four NATs have been identified: NatA, NatB, NatC, and NatD. In this study, the
      N(alpha)-acetylation status of ribosomal protein was analyzed using NAT mutants
      combined with two-dimensional difference gel electrophoresis (2D-DIGE) and mass
      spectrometry (MS). A total of 60 ribosomal proteins were identified, of which 17
      were N(alpha)-acetylated by NatA, and two by NatB. The N(alpha)-acetylation of
      two of these, S17 and L23, by NatA was not previously observed. Furthermore, we
      tested the effect of ribosomal protein N(alpha)-acetylation on protein synthesis
      using the purified ribosomes from each NAT mutant. It was found that the protein
      synthesis activities of ribosomes from NatA and NatB mutants were decreased by
      27% and 23%, respectively, as compared to that of the normal strain. Furthermore,
      we have shown that ribosomal protein N(alpha)-acetylation by NatA influences
      translational fidelity in the presence of paromomycin. These results suggest that
      ribosomal protein N(alpha)-acetylation is necessary to maintain the ribosome's
      protein synthesis function.

PMID- 21184852
TI  - Strategy for purification and mass spectrometry identification of SELDI peaks
      corresponding to low-abundance plasma and serum proteins.
AB  - Analysis by SELDI-TOF-MS of low abundance proteins makes it possible to select
      peaks as candidate biomarkers. Our aim was to define a purification strategy to
      optimise identification by MS of peaks detected by SELDI-TOF-MS from plasma or
      serum, regardless of any treatment by a combinatorial peptide ligand library
      (CPLL). We describe 2 principal steps in purification. First, choosing the
      appropriate sample containing the selected peak requires setting up a databank
      that records all the m/z peaks detected from samples in different conditions.
      Second, the specific purification process must be chosen: separation was achieved
      with either chromatographic columns or liquid-phase isoelectric focusing, both
      combined when appropriate with reverse-phase chromatography. After purification,
      peaks were separated by gel electrophoresis and the candidate proteins were
      analyzed by nano-liquid-chromatography-MS/MS. We chose 4m/z peaks (9400, 13,571,
      13,800 and 15,557) selected for their differential expression between two
      conditions, as examples to explain the different strategies of purification, and
      we successfully identified 3 of them. Despite some limitations, our strategy to
      purify and identify peaks selected from SELDI-TOF-MS analysis was effective.

PMID- 21184853
TI  - Proteolytic and non-proteolytic roles of ubiquitin and the ubiquitin proteasome
      system in transcriptional regulation.
AB  - The ubiquitin proteasome system (UPS) regulates perhaps the most intriguing
      balance in all of biology: how cells control protein function and malfunction in
      order to regulate, and eventually eliminate, the old and error prone while
      simultaneously synthesizing and orchestrating the new. In light of the growing
      notion that ubiquitination and the 26S proteasome are central to a multiplicity
      of diverse cellular functions, we discuss here the proteolytic and non
      proteolytic roles of the UPS in regulating pathways ultimately involved in
      protein synthesis and activity including roles in epigenetics, transcription, and
      post-translational modifications. This article is part of a Special Issue
      entitled The 26S Proteasome: When degradation is just not enough!

PMID- 21184854
TI  - A rare cause of a gastric submucosal tumor.

PMID- 21184855
TI  - Divergence of immunologic and protective responses of different BCG strains in a
      murine model.
AB  - The ongoing evolution of BCG after its introduction in 1921 resulted in strains
      that differ genetically and phenotypically. Based on a genomic deletion (Region
      of Difference 2 or RD2) that occurred between 1927 and 1931, BCG strains can be
      sub-classified by the presence or absence of RD2. The existence of other
      mutations that distinguish BCG strains precludes simple comparison of RD2
      positive and RD2-negative BCG strains to determine the importance, if any, of RD2
      for vaccine protection. In this study, we have compared the RD2-containing BCG
      Russia, BCG Pasteur (which is a natural mutant for RD2), and BCG Pasteur
      complemented with RD2-genes Rv1979c-Rv1982 through various in vitro and in vivo
      assays of immunogenicity and protection. We determined that the presence of RD2
      did not affect vaccine persistence, but lead to increased immunogenicity, as
      measured by ELISpot. Additionally, T-cells from animals immunized with BCG Russia
      and BCG Pasteur::Rv1979c-82 were more effective at killing Mycobacterium
      tuberculosis in macrophages than T-cells from animals immunized with BCG Pasteur.
      In a mouse vaccine-challenge model, the presence of RD2 had no effect on
      pulmonary TB, as measured by M. tuberculosis burden and degree of histopathology,
      at 4, 8 or 12 weeks post-infection. The presence of RD2 was however associated
      with decreased dissemination of M. tuberculosis to the spleen. Together, our data
      demonstrated that the loss of RD2 resulted in decreased immunogenicity but did
      not affect protection against pulmonary TB, indicating a dissociation between
      these phenotypes associated with BCG vaccination.

PMID- 21184856
TI  - Anti-adenovirus humoral responses influence on the efficacy of vaccines based on
      epitope display on adenovirus capsid.
AB  - The efficacy of recombinant adenoviruses (Ads) vaccine vectors is diminished by
      the high prevalence of anti-Ad antibodies (Abs) that hampers gene transfer.
      Epitope display on Ad capsid constitutes an alternative approach to bypass anti
      Ad Ab capacity from blocking antigen expression. To understand the role of the
      epitope insertion site, an ovalbumin-derived epitope was genetically inserted
      into either Ad hexon or fiber proteins. Hexon-modified Ads triggered higher anti
      ovalbumin Ab responses after one injection but surprisingly fiber-modified Ads
      were by far more potent after two or several administrations. Our data unravel a
      role for anti-Ad humoral immunity in controlling anti-epitope humoral responses.

PMID- 21184857
TI  - Immunogenic and replicative properties of classical swine fever virus replicon
      particles modified to induce IFN-alpha/beta and carry foreign genes.
AB  - Virus replicon particles (VRP) are genetically engineered infectious virions
      incapable of generating progeny virus due to partial or complete deletion of at
      least one structural gene. VRP fulfil the criteria of a safe vaccine and gene
      delivery system. With VRP derived from classical swine fever virus (CSF-VRP), a
      single intradermal vaccination protects from disease. Spreading of the challenge
      virus in the host is however not completely abolished. Parameters that are
      critical for immunogenicity of CSF-VRP are not well characterized. Considering
      the importance of type I interferon (IFN-alpha/beta) to immune defence
      development, we generated IFN-alpha/beta-inducing VRP to determine how this would
      influence vaccine efficacy. We also evaluated the effect of co-expressing
      granulocyte macrophage colony-stimulating factor (GM-CSF) in the vaccine context.
      The VRP were capable of long-term replication in cell culture despite the
      presence of IFN-alpha/beta. In vivo, RNA replication was essential for the
      induction of an immune response. IFN-alpha/beta-inducing and GM-CSF-expressing
      CSF-VRP were similar to unmodified VRP in terms of antibody and peripheral T-cell
      responses, and in reducing the blood levels of challenge virus RNA. Importantly,
      the IFN-alpha/beta-inducing VRP did show increased efficacy over the unmodified
      VRP in terms of B-cell and T-cell responses, when tested with secondary immune
      responses by in vitro restimulation assay.

PMID- 21184858
TI  - Induction of immune memory by a multisubunit chlamydial vaccine.
AB  - We tested the hypothesis that intramuscular immunization with a multisubunit
      chlamydial vaccine candidate will induce long lasting immune responses in mice.
      Accordingly, groups of female C57BL/6 mice were immunized intramuscularly with
      Vibrio cholerae ghosts (VCG) expressing the Poring B and polymorphic membrane
      protein-D proteins of Chlamydia trachomatis or a control antigen. Humoral and
      cell-mediated immune responses were evaluated following immunization and after
      live chlamydial infection. Immunization induced an anamnestic response
      characterized by chlamydial-specific IgG2a and IgA antibodies in sera and vaginal
      lavage as well as specific genital and splenic T cell responses. The results also
      revealed that the local mucosal and systemic cellular and humoral immune
      effectors induced in mice following immunization with the vaccine candidate are
      long lasting. Vaccinated mice cleared intravaginal challenge with 10(5)
      chlamydial inclusion forming units within 12 days compared to control mice, which
      shed up to 2 * 10(3) IFUs at this time point. Moreover, rechallenge of mice 98
      days after resolution of the primary infection resulted in the recall and
      retention of a relatively high frequency of chlamydial-specific Th1 cells and
      IgG2a in the genital mucosa. These results provide the first evidence that a VCG
      based multisubunit chlamydial vaccine is capable of effectively stimulating
      anamnestic systemic and mucosal immune responses in mice. The data support
      further vaccine evaluation and testing for induction of long-term protective
      immunity.

PMID- 21184859
TI  - Comment on: the cost effectiveness of rotavirus vaccination: comparative analyses
      for five European countries and transferability in Europe.

PMID- 21184861
TI  - Introduction: Comparative effectiveness research-objectives, challenges, and
      contributions of the US Department of Veterans Affairs.

PMID- 21184862
TI  - Observational methods in comparative effectiveness research.
AB  - Comparative effectiveness research (CER) may be defined informally as an
      assessment of available options for treating specific medical conditions in
      selected groups of patients. In this context, the most prominent features of CER
      are the various patient populations, medical ailments, and treatment options
      involved in any particular project. Yet, each research investigation also has a
      corresponding study design or "architecture," and in patient-oriented research a
      common distinction used to describe such designs are randomized controlled trials
      (RCTs) versus observational studies. The purposes of this overview, with regard
      to CER, are to (1) understand how observational studies can provide accurate
      results, comparable to RCTs; (2) recognize strategies used in selected newer
      methods for conducting observational studies; (3) review selected observational
      studies from the Veterans Health Administration; and (4) appreciate the
      importance of fundamental methodological principles when conducting or evaluating
      individual studies.

PMID- 21184863
TI  - Scientific and organizational collaboration in comparative effectiveness
      research: the VA cooperative studies program model.
AB  - Comparative effectiveness research (CER) has the ability to improve health and
      inform patients, clinicians, and decision makers. However, calls for more devoted
      efforts with regard to CER have been countered by methodological, resource, and
      translational challenges related to conducting these studies. The Department of
      Veterans Affairs (VA) Cooperative Studies Program (CSP) is a clinical research
      infrastructure that has contributed much evidence to support clinical practice
      for several decades. Although the CSP does not exclusively focus on CER, it
      employs strategies that lend themselves toward the planning and execution of
      studies that seek to compare interventions and/or strategies for treating
      disease. Consequently, the CSP provides a model for addressing important
      scientific, structural, and operational factors for clinical research, including
      large, national and multinational comparative effectiveness studies. Exploration
      of the difficulties the CSP has encountered can help to elucidate barriers that
      face CER. This article discusses factors and approaches for collaboratively
      developing and conducting definitive studies that produce outcomes aimed at
      influencing clinical practice, lessons that have resulted from such efforts, and
      ongoing challenges. Future program directions are also presented to highlight
      areas of emphasis and implications for CER within the VA and nationally.

PMID- 21184864
TI  - The past, present, and future of comparative effectiveness research in the US
      Department of Veterans Affairs.
AB  - A particular challenge for the healthcare provider and the patient is to choose
      among competing therapeutic approaches for a particular condition. Often, the
      relative benefits and risks of potential therapies are not uniformly available
      from the existing scientific information. Many have pointed to the need for more
      comparative effectiveness research (CER) to aide in these decisions. The US
      Department of Veterans Affairs (VA) has a long history of conducting CER. The
      success of the VA CER program has been facilitated by several important aspects
      of scientific infrastructure related to (1) research question refinement, (2)
      study design, planning and coordination, (3) evidence synthesis, and (4)
      implementation research. In publications that had VA coauthors in 2 major medical
      journals, 25% of the published studies were classified as CER. The most frequent
      categories of study were pharmaceutical and behavioral interventions. In the
      future, the CER enterprise will move toward increased input from clinicians in
      research topic choice and enhanced consideration of other methodologies besides
      the randomized controlled trial.

PMID- 21184865
TI  - Comparative effectiveness research and medical informatics.
AB  - As is the case for environmental, ecological, astronomical, and other sciences,
      medical practice and research finds itself in a tsunami of data. This data
      deluge, due primarily to the introduction of digitalization in routine medical
      care and medical research, affords the opportunity for improved patient care and
      scientific discovery. Medical informatics is the subdiscipline of medicine
      created to make greater use of information in order to improve healthcare. The 4
      areas of medical informatics research (information access, structure, analysis,
      and interaction) are used as a framework to discuss the overlap in information
      needs of comparative effectiveness research and potential contributions of
      medical informatics. Examples of progress from the medical informatics literature
      and the Veterans Affairs Healthcare System are provided.

PMID- 21184866
TI  - Implementation research: a critical component of realizing the benefits of
      comparative effectiveness research.
AB  - Comparative effectiveness research (CER) holds the promise of improving patient
      centered care and increasing value in the healthcare system. Achieving these
      goals, however, depends on effectively implementing the findings of CER. In this
      article, we draw on lessons from implementation research and our experience in
      the Veterans Administration (VA) healthcare system to offer recommendations about
      what is needed to support implementation of CER. There is no single strategy for
      successful implementation. Implementation efforts must take into account the
      nature of the evidence, the type of change being implemented, the clinical
      context in which the findings are being applied, and the specific barriers and
      facilitators to implementing new practices. The experience of the VA illustrates
      the importance of taking a systems approach that aligns numerous elements of the
      healthcare system--guidelines, decision support, performance measures, financial
      incentives, coverage and benefits policy, and health information technology--to
      support implementation:. We illustrate these principles with an example of
      implementing a new model of evidence-based depression care.

PMID- 21184860
TI  - The role of chalcones in suppression of NF-kappaB-mediated inflammation and
      cancer.
AB  - Although consumption of fruits, vegetables, spices, cereals and pulses has been
      associated with lower incidence of cancer and other chronic diseases, how these
      dietary agents and their active ingredients minimize these diseases, is not fully
      understood. Whether it is oranges, kawa, hops, water-lilly, locorice, wax apple
      or mulberry, they are all connected by a group of aromatic ketones, called
      chalcones (1,3-diaryl-2-propen-1-ones). Some of the most significant chalcones
      identified from these plants include flavokawin, butein, xanthoangelol, 4
      hydroxyderricin, cardamonin, 2',4'-dihydroxychalcone, isoliquiritigenin,
      isosalipurposide, and naringenin chalcone. These chalcones have been linked with
      immunomodulation, antibacterial, antifungal, antiviral, anti-inflammatory,
      antioxidant, anticancer, and antidiabetic activities. The current review,
      however, deals with the role of various chalcones in inflammation that controls
      both the immune system and tumorigenesis. Inflammatory pathways have been shown
      to mediate the survival, proliferation, invasion, angiogenesis and metastasis of
      tumors. How these chalcones modulate inflammatory pathways, tumorigenesis and
      immune system is the focus of this review.

PMID- 21184867
TI  - Methodological issues in comparative effectiveness research: clinical trials.
AB  - The US Department of Veterans Affairs (VA) Cooperative Studies Program has been
      conducting comparative effectiveness clinical trials for nearly 4 decades in many
      disease areas, including cardiovascular disease/surgery, diabetes mellitus,
      mental health, neurologic disorders, cancer, infectious diseases, and rheumatoid
      arthritis. The features that have made this program advantageous for conducting
      comparative effectiveness clinical trials are described along with methodological
      considerations for future trials based on lessons learned from its experience
      conducting these types of studies. Some of the lessons learned involve managing
      risk factors, clinical equipoise, patient preferences, evolving technology, the
      use of usual care as a comparator and pharmaceutical issues related to study drug
      blinding. These issues are not unique to the VA but can play an important role in
      enabling valid comparisons between treatments that may have differences in
      delivery or mechanisms of action and could affect the execution and feasibility
      of conducting a clinical trial with a comparative effectiveness aim. We also
      outline some future directions for comparative effectiveness clinical trials.

PMID- 21184868
TI  - Endoscopic assessment and grading of Barrett's esophagus using magnification
      endoscopy and narrow-band imaging: accuracy and interobserver agreement of
      different classification systems (with videos).
AB  - BACKGROUND: Three different classification systems for the evaluation of
      Barrett's esophagus (BE) using magnification endoscopy (ME) and narrow-band
      imaging (NBI) have been proposed. Until now, no comparative and external
      evaluation of these systems in a clinical-like situation has been performed.
      OBJECTIVE: To compare and validate these 3 classification systems. DESIGN:
      Prospective validation study. SETTING: Tertiary-care referral center. Nine
      endoscopists with different levels of expertise from Europe and Japan
      participated as assessors. PATIENTS: Thirty-two patients with long-segment BE.
      INTERVENTIONS: From a group of 209 standardized prospective recordings collected
      on BE by using ME combined with NBI, 84 high-quality videos were randomly
      selected for evaluation. Histologically, 28 were classified as gastric type
      mucosa, 29 as specialized intestinal metaplasia (SIM), and 27 as SIM with
      dysplasia/cancer. Assessors were blinded to underlying histology and scored each
      video according to the respective classification system. Before evaluation, an
      educational set concerning each classification system was carefully studied. At
      each assessment, the same 84 videos were displayed, but in different and random
      order. MAIN OUTCOME MEASUREMENTS: Accuracy for detection of nondysplastic and
      dysplastic SIM. Interobserver agreement related to each classification. RESULTS:
      The median time for video evaluation was 25 seconds (interquartile range 20-39
      seconds) and was longer with the Amsterdam classification (P < .001). In 65% to
      69% of the videos, assessors described certainty about the histology prediction.
      The global accuracy was 46% and 47% using the Nottingham and Kansas
      classifications, respectively, and 51% with the Amsterdam classification. The
      accuracy for nondysplastic SIM identification ranged between 57% (Kansas and
      Nottingham) and 63% (Amsterdam). Accuracy for dysplastic tissue was 75%,
      irrespective of the classification system and assessor expertise level.
      Interobserver agreement ranged from fair (Nottingham, kappa = 0.34) to moderate
      (Amsterdam and Kansas, kappa = 0.47 and 0.44, respectively). LIMITATION: No per
      patient analysis. CONCLUSIONS: All of the available classification systems could
      be used in a clinical-like environment, but with inadequate interobserver
      agreement. All classification systems based on combined ME and NBI, revealed
      substantial limitations in predicting nondysplastic and dysplastic BE when
      assessed externally. This technique cannot, as yet, replace random biopsies for
      histopathological analysis.

PMID- 21184869
TI  - Sedation during upper GI endoscopy in cirrhotic outpatients: a randomized,
      controlled trial comparing propofol and fentanyl with midazolam and fentanyl.
AB  - BACKGROUND: Patients with liver cirrhosis frequently undergo diagnostic or
      therapeutic upper GI endoscopy (UGIE), and the liver disease might impair the
      metabolism of drugs usually administered for sedation. OBJECTIVE AND SETTING: To
      compare sedation with a combination of propofol plus fentanyl and midazolam plus
      fentanyl in cirrhotic outpatients undergoing UGIE. DESIGN: A prospective,
      randomized, controlled trial was conducted between February 2008 and February
      2009. MAIN OUTCOMES MEASUREMENTS: Efficacy (proportion of complete procedures
      using the initial proposed sedation scheme), safety (occurrence of sedation
      related complications), and recovery time were measured. RESULTS: Two hundred ten
      cirrhotic patients referred for UGIE were randomized to 2 groups: midazolam group
      (0.05 mg/kg plus fentanyl 50 MUg intravenously) or propofol group (0.25 mg/kg
      plus fentanyl 50 MUg intravenously). There were no differences between groups
      regarding age, sex, weight, etiology of cirrhosis, and Child-Pugh or American
      Society of Anesthesiologists classification. Sedation with propofol was more
      efficacious (100% vs 88.2%; P < .001) and had a shorter recovery time than
      sedation with midazolam (16.23 +/- 6.84 minutes and 27.40 +/- 17.19 minutes,
      respectively; P < .001). Complication rates were similar in both groups (14% vs
      7.3%; P = .172). LIMITATIONS: Single-blind study; sample size. CONCLUSION: Both
      sedation schemes were safe in this setting. Sedation with propofol plus fentanyl
      was more efficacious with a shorter recovery time compared with midazolam plus
      fentanyl. Therefore, the former scheme is an alternative when sedating cirrhotic
      patients undergoing UGIE.

PMID- 21184870
TI  - Accuracy of contrast-enhanced harmonic EUS with a second-generation perflutren
      lipid microsphere contrast agent (with video).
AB  - BACKGROUND: EUS-FNA has limitations in cancer diagnosis/staging. New contrast
      agents, transducers, and processors have improved the potential of contrast
      enhanced harmonic (CEH)-EUS. OBJECTIVE: To determine optimal settings and
      preliminary accuracy of CEH-EUS by using a second-generation perflutren lipid
      microsphere contrast agent and a prototype linear echoendoscope. DESIGN:
      Prospective, comparative, pilot study. SETTING: Tertiary-care medical center.
      PATIENTS: This study involved patients with esophageal/pancreatic/liver tumors or
      adenopathy. INTERVENTION: Contrast agent was injected (10 MUL/kg intravenously in
      1-2 doses), and the mechanical index was optimized over 5 cases (0.3).
      Intermittent/continuous imaging was used with extended pure harmonic detection.
      MAIN OUTCOME MEASUREMENTS: Before-contrast and after-contrast predictions of
      neoplasia (5-point Likert scale). The reference standard was positive tissue or 6
      month follow-up. Perfusion factors (sequence, pattern, washout) were noted, and
      phases were video recorded (arterial, venous, and postvenous). RESULTS: Thirty
      sites (7 nodes and 16 pancreatic and 7 nonpancreatic masses) were imaged in 21
      patients; 21 of 30 had FNA, and 5 had surgery. Four cases (13.3%) were rated as
      undecided/indeterminate with EUS (vs 1 [3.3%] with CEH-EUS; P = .35). Twenty-four
      cases with confirmed diagnoses (12 malignant and 12 benign) were used for test
      performance: positive/negative predictive values for CEH-EUS were 80.0% (95%
      confidence interval, 51.9%-95.7%)/100.0% (95% confidence interval, 63.0%-100.0%)
      versus 84.6%/100.0% for EUS. Accuracies, counting "undecided" (1 in CEH-EUS and 4
      in EUS) as incorrect, were 83.3% and 79.2%. In 2 cases, management would change
      significantly: (1) liver hemangioma, avoiding FNA; and (2) mediastinal "cyst"
      confirmed as solid. LIMITATIONS: Small sample. Tissue not always available.
      CONCLUSION: CEH-EUS adds minimal imaging time and is accurate, with small
      improvement over EUS. Added information in vascular and cystic lesions can
      potentially change management.

PMID- 21184871
TI  - Anchoring flap versus flared end, fully covered self-expandable metal stents to
      prevent migration in patients with benign biliary strictures: a multicenter,
      prospective, comparative pilot study (with videos).
AB  - BACKGROUND: Recently, placement of fully covered self-expandable metal stents
      (FCSEMSs) has been proposed as an alternative treatment for the management of
      benign biliary strictures. However, the major limitations of FCSEMSs are frequent
      migration and removal complications. OBJECTIVE: We conducted this study to
      compare the antimigration effects, complication rates, and short-term efficacy of
      2 FCSEMSs with either an anchoring flap (AF) or a flared end (FE) at the proximal
      end of the stent. DESIGN: A multicenter, prospective comparative pilot study.
      SETTING: Two tertiary referral centers. PATIENTS: A total of 43 patients with
      benign biliary stricture who were candidates for placement of FCSEMSs were
      assigned to the AF (n = 22) or the FE group (n = 21). INTERVENTIONS: Predefined
      duration of placement and removal of FCSEMSs. RESULTS: After a median period of
      placement of 6 months (interquartile range 4-6), no patients in the AF group and
      33% of patients (7 of 21, 1 in proximal and 6 in distal) in the FE group had
      stent migration (P = .004). The removal rate of the FCSEMSs was 100% in both
      groups (per protocol, n = 22 in the AF group and n = 17 in the FE group).
      Immediate improvement of biliary stricture was 91% (20/22, per protocol) in the
      AF group and 88% (15/17, per protocol) in the FE group. All stents were removed
      without difficulty. LIMITATIONS: Short-term follow-up after the removal of
      FCSEMSs. CONCLUSIONS: With regard to the antimigration effect of FCSEMSs for
      benign biliary stricture, the AF design may be superior to the FE. For up to 6
      months, both FCSEMSs can be endoscopically removed without complications. (
      CLINICAL TRIAL REGISTRATION NUMBER: NCT00945516.).

PMID- 21184872
TI  - The target sign: an endoscopic marker for the resection of the muscularis propria
      and potential perforation during colonic endoscopic mucosal resection.
AB  - BACKGROUND: EMR of large sessile polyps and laterally spreading tumors (LSTs) of
      the colon is safe and cost-effective. Perforation remains a feared and well
      recognized complication; however, endoscopic detection is often absent, and most
      commonly, diagnosis is delayed and depends on clinical signs and/or radiology
      findings. To date, an endoscopic sign to identify muscularis propria (MP)
      resection and potential perforation has not been described. OBJECTIVE: To
      describe an endoscopic sign for prompt recognition of EMR-related MP resection.
      DESIGN: Prospective analysis. SETTINGS: Tertiary referral academic
      gastroenterology unit. PATIENTS: Patients with the target sign were identified
      prospectively in 2 large prospective studies of EMR for colonic LSTs 20 mm or
      larger. INTERVENTION: A standardized EMR approach was used. MP defects were
      closed endoscopically with clips. MAIN OUTCOME MEASUREMENTS: The presence or
      absence of the target sign in the polypectomy specimen and its influence on
      subsequent endoscopic management of polypectomy complications. RESULTS: A total
      of 445 patients with LSTs or sessile polyps 20 mm or larger (mean size 33 mm,
      range 20-85 mm) were prospectively enrolled in 2 studies. Ten patients (mean age
      70.3 years, range 48-83 years, 50% male) with target lesions and histologically
      confirmed MP resection were identified prospectively at the time of EMR, with 3
      having full-thickness resection. All cases were identified intraprocedurally by a
      target sign on the underside of the specimen and a mirror target evident in the
      mucosal defect. All patients were treated endoscopically with 1 to 5 endoscopic
      clips. None required operative management. Thirteen inpatient days were required
      to treat the 10 patients (mean 1.3 days). LIMITATIONS: Nonrandomized study.
      CONCLUSIONS: Careful analysis of the post-EMR specimen and resection defect may
      reveal a target sign, an easily recognized and reliable marker of either partial-
      or full-thickness MP resection and potential perforation. Prompt recognition of
      this sign facilitates endoscopic management.

PMID- 21184873
TI  - The target sign: a new weapon for early diagnosis of colonic perforation during
      EMR.

PMID- 21184874
TI  - Preferences for ethnicity and sex of endoscopists in a Hispanic population in the
      United States.
AB  - BACKGROUND: Preferences toward endoscopists have been shown to be a barrier to
      colorectal cancer screening in certain patient populations. OBJECTIVE: To
      evaluate sex and ethnicity preferences for endoscopists in a largely Hispanic
      population. METHODS: This was a prospective cross-sectional study. Patients were
      given an anonymous questionnaire in which information on demographics and
      sex/ethnic preferences for endoscopists was determined. Bivariate and
      multivariate models were used to assess factors that affected outcome variables.
      RESULTS: A total of 438 patients were included (213 men, 225 women; mean age 62
      years). Predominant ethnicities were white (44%) and Hispanic (45%). Twenty-six
      percent and 17% of patients expressed sex and ethnicity preferences,
      respectively. Women (30.8%), particularly Hispanic women (35%), had a sex
      preference more often than men (20.4%; P < .05). Hispanics had an ethnicity
      preference more often than white patients (P < .01). Lower education level, being
      a first-generation immigrant, family history of colorectal cancer, having a
      concurrent preference for obstetrician/gynecologist, and ethnicity preference for
      endoscopist were associated with the presence of a sex preference for the
      endoscopist (P < .05). Being a first-generation immigrant and having an ethnicity
      preference for a primary care provider or the sex of the endoscopist were
      significantly associated with a preference for the ethnicity of the endoscopist
      (P < .05). LIMITATIONS: Results are based on self-report. Limited study factors
      were also assessed. CONCLUSIONS: Among a predominant Hispanic population, sex and
      ethnicity preferences for endoscopists are often seen. They may coexist, increase
      the likelihood of the presence of one when the other is present, and likely
      influence compliance with colorectal cancer screening.

PMID- 21184875
TI  - Laparoscopic-assisted percutaneous endoscopic cecostomy in children with
      defecation disorders (with video).
AB  - BACKGROUND: The antegrade continence enema (ACE) procedure has been widely used
      in the management of children with defecation disorders. The ACE procedure has
      undergone many technical modifications. We developed a safe and minimally
      invasive technique, the laparoscopic-assisted percutaneous endoscopic cecostomy
      (LAPEC). OBJECTIVE: To compare LAPEC to laparoscopic cecostomy in terms of
      operative time, hospital length of stay, and procedure-related morbidity. DESIGN:
      Retrospective review of children undergoing the ACE procedure. SETTING: Two
      tertiary-care centers. PATIENTS: This study involved children with defecation
      disorders. INTERVENTION: The ACE procedure. MAIN OUTCOME MEASUREMENTS: Procedure
      complications, length of stay, and operative time. RESULTS: Fifty patients
      underwent LAPEC, and 15 underwent laparoscopic cecostomy. Of the LAPEC patients,
      70% were male, with mean age 12 +/- 4.2 years, mean operative time 100.1 +/- 16.6
      minutes, and mean length of stay 3.4 +/- 1.4 days. Of the laparoscopic cecostomy
      patients, 56% were male, with mean age 10.5 +/- 4 years, mean operative time
      100.8 +/- 19.1 minutes, and mean length of stay 3.8 +/- 1.6 days. There was no
      statistical difference between the 2 groups. The single intraoperative
      complication during LAPEC was a cecal hematoma. Postoperative complications after
      LAPEC included 6 patients with low-grade fever, 3 patients with tube dislodgement
      (2 treated by repeat LAPEC and the other by open surgery), and 2 patients with
      skin breakdown. Of the 50 LAPEC patients and their families, 48 were satisfied
      with the outcome. LIMITATIONS: Retrospective study. CONCLUSION: LAPEC is a safe,
      minimally invasive procedure for cecostomy placement in children with refractory
      constipation or fecal incontinence.

PMID- 21184876
TI  - A randomized, controlled trial to confirm the beneficial effects of the water
      method on U.S. veterans undergoing colonoscopy with the option of on-demand
      sedation.
AB  - BACKGROUND: Sedation for colonoscopy discomfort imposes a recovery-time burden on
      patients. The water method permitted 52% of patients accepting on-demand sedation
      to complete colonoscopy without sedation. On-site and at-home recovery times were
      not reported. OBJECTIVE: To confirm the beneficial effect of the water method and
      document the patient recovery-time burden. DESIGN: Randomized, controlled trial,
      with single-blinded, intent-to-treat analysis. SETTING: Veterans Affairs
      outpatient endoscopy unit. PATIENTS: This study involved veterans accepting on
      demand sedation for screening and surveillance colonoscopy. INTERVENTION: Air
      versus water method for colonoscope insertion. MAIN OUTCOME MEASUREMENTS:
      Proportion of patients completing colonoscopy without sedation, cecal intubation
      rate, medication requirement, maximum discomfort (0 = none, 10 = severe),
      procedure-related and patient-related outcomes. RESULTS: One hundred veterans
      were randomized to the air (n = 50) or water (n = 50) method. The proportions of
      patients who could complete colonoscopy without sedation in the water group (78%)
      and the air group (54%) were significantly different (P = .011, Fisher exact
      test), but the cecal intubation rate was similar (100% in both groups). Secondary
      analysis (data as Mean [SD]) shows that the water method produced a reduction in
      medication requirement: fentanyl, 12.5 (26.8) MUg versus 24.0 (30.7) MUg;
      midazolam, 0.5 (1.1) mg versus 0.94 (1.20) mg; maximum discomfort, 2.3 (1.7)
      versus 4.9 (2.0); recovery time on site, 8.4 (6.8) versus 12.3 (9.4) minutes; and
      recovery time at home, 4.5 (9.2) versus 10.9 (14.0) hours (P = .049; P = .06; P =
      .0012; P = .0199; and P = .0048, respectively, t test). LIMITATIONS: Single
      Veterans Affairs site, predominantly male population, unblinded examiners.
      CONCLUSION: This randomized, controlled trial confirms the reported beneficial
      effects of the water method. The combination of the water method with on-demand
      sedation minimizes the patient recovery-time burden. ( CLINICAL TRIAL
      REGISTRATION NUMBER: NCT00920751.).

PMID- 21184877
TI  - A prospective, randomized assessment of a spatial orientation device in natural
      orifice transluminal endoscopic surgery.
AB  - BACKGROUND: One of the challenges in natural orifice transluminal endoscopic
      surgery (NOTES) is spatial orientation. The Queen's NOTES group has devised a
      novel method of orientation by using a magnetic device that passes within an
      endoscope channel allowing for 3-dimensional imaging of the shape and orientation
      of the endoscope. OBJECTIVE: To assess the feasibility and utility of a novel
      orientation device. DESIGN: Randomized, controlled trial. SETTING: Animal
      research laboratory study on four 25-kg pigs. INTERVENTION: The device was tested
      by 6 endoscopists and 6 laparoscopic surgeons. Starting at the gastrotomy, the
      time to identify 4 targets was recorded. Participants were required to identify
      and touch the gallbladder, the fallopian tube, a clip on the abdominal wall, and
      the liver edge. Use of the orientation device was randomized for each session.
      MAIN OUTCOME MEASUREMENTS: Time to identify targets with and without the device.
      Secondary analysis assessed differences between medical specialties and level of
      training. RESULTS: The mean time to identify all 4 targets with the device was
      75.08 +/- 42.68 seconds versus 100.20 +/- 60.70 seconds without the device (P
      <.001). The mean time to identify all 4 targets on the first attempt was 102.29
      +/- 61.36 seconds versus 72.99 +/- 40.19 seconds on the second attempt (P <.001).
      No differences based on specialty or level of training were identified.
      LIMITATIONS: Small sample size and simplicity of tasks. CONCLUSION: Regardless of
      randomization order, both groups were faster with the device. These encouraging
      results warrant further study using more complex scenarios.

PMID- 21184878
TI  - Development and validation of a training module on the use of narrow-band imaging
      in differentiation of small adenomas from hyperplastic colorectal polyps.
AB  - BACKGROUND: Experts are accurate in differentiating small adenomas from
      hyperplastic polyps at colonoscopy by using narrow-band imaging (NBI). OBJECTIVE:
      To prospectively evaluate the effectiveness of an NBI training module on
      individuals with varying colonoscopy experience. DESIGN: Prospective educational
      evaluation study. SETTING: Academic endoscopy unit. PARTICIPANTS: Twenty-one
      participants of varying colonoscopy experience (novices, trainees, and
      experienced gastroenterologists) and 5 experts in NBI. INTERVENTION: Participants
      completed a computer-based test module consisting of 30 NBI polyp images. No
      feedback was given. They then completed a computer-based training module on the
      use of NBI in the differentiation of adenomas and hyperplastic polyps. The test
      module was then completed a second time. MAIN OUTCOME MEASUREMENTS: Construct
      validity (the difference in baseline accuracy on the test module between
      different groups of participants) and content validity (difference in accuracy
      achieved on the test module before and after training) of the training module.
      RESULTS: There was a significant difference in the baseline accuracy (P < .001)
      between experts (0.95; 95% confidence interval [CI], 0.92-0.97), experienced
      colonoscopists (0.68; 95% CI, 0.68-0.74), trainees (0.75; 95% CI, 0.67-0.82), and
      novices (0.62; 95% CI, 0.46-0.77). Accuracy increased significantly (P < .001)
      for all 3 groups after training (novices 0.84; 95% CI, 0.78-0.88, trainees 0.90;
      95% CI, 0.84-0.93, and experienced colonoscopists 0.84; 95% CI, 0.76-0.89). After
      training, the agreement was moderate at least (kappa = 0.56 for novices, kappa =
      0.70 for trainees, and kappa = 0.54 for experienced colonoscopists). LIMITATIONS:
      This study did not assess the accuracy of optical diagnosis in routine clinical
      practice. CONCLUSION: A short, computer-based training module can improve the
      diagnostic accuracy and interobserver agreement for the use of NBI to
      differentiate adenomas from hyperplastic polyps and could be used for the initial
      training in optical diagnosis.

PMID- 21184879
TI  - Increasing exposure of gastroenterology fellows to abdominal imaging.

PMID- 21184880
TI  - A novel balloon pull-through technique for esophageal dilation in eosinophilic
      esophagitis (with video).
AB  - BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic inflammatory condition
      that can be complicated by esophageal strictures requiring endoscopic dilation.
      Whereas recent data have advanced the notion that dilation can be done
      effectively with minimal morbidity, issues concerning safety and tolerability
      remain. OBJECTIVE: To review our initial experience with a novel esophageal
      balloon pull-through technique for sizing and dilation in EoE as well as to
      present a video illustrating the methodology. DESIGN: Case series. SETTING:
      Tertiary-care referral center. PATIENTS: Thirteen patients with EoE.
      INTERVENTION: Balloon pull-through technique for esophageal dilation. MAIN
      OUTCOME MEASUREMENTS: Dilation effect, size, and complications (esophageal
      perforation, bleeding requiring endoscopic hemostasis, or severe chest pain
      requiring hospitalization). RESULTS: Thirteen patients (7 men, 6 women; mean age
      40 years, range 19-66 years) with EoE underwent dilation with the esophageal
      balloon pull-through technique. Resistance during the pull-through was
      encountered in 11 patients (85%), even though no discrete areas of narrowing were
      encountered. A tear was achieved in 9 patients (69%). Nine patients (69%)
      reported improvement in their dysphagia after dilation. There were no serious
      complications from the procedure. LIMITATIONS: Retrospective, single center,
      small patient numbers in this initial report. CONCLUSIONS: The esophageal balloon
      pull-through technique for esophageal dilation in patients with EoE appears to be
      safe and effective. It is a rational approach to gauging the luminal diameter of
      the esophagus and treating strictures in patients with EoE and dysphagia, but
      further prospective study is required to confirm these initial results.

PMID- 21184881
TI  - Endoscopically applied radiofrequency ablation appears to be safe in the
      treatment of malignant biliary obstruction.
AB  - BACKGROUND: In unresectable malignant bile duct obstruction in a patient with a
      life expectancy longer than 3 months, the use of self-expandable metal stents
      (SEMSs) is the standard technique to ensure continued biliary drainage. As many
      as 50% of patients with SEMSs will present with stent occlusion within 6 months.
      Changes to stent design and composition and concomitant therapy have failed to
      improve stent patency; therefore, alternative techniques to safely prolong stent
      patency are required. OBJECTIVE: To demonstrate the safety of endobiliary bipolar
      radiofrequency ablation (RFA) in patients with malignant biliary obstruction and
      to report the 90-day biliary patency of this novel procedure. DESIGN: Open-label
      pilot study. SETTING: Single tertiary care unit. PATIENTS: A total of 22 patients
      with unresectable malignant bile duct obstruction. INTERVENTIONS: Bipolar RFA
      within the bile duct. MAIN OUTCOME MEASUREMENTS: Immediate and 30-day
      complications and 90-day stent patency. RESULTS: A total of 22 patients (16
      pancreatic, 6 cholangiocarcinoma) were recruited between January 2009 and April
      2010. Deployment of an RFA catheter was successful in 21 patients. SEMS placement
      was achieved in all cases of successful RFA catheter deployment. One patient
      failed to demonstrate successful biliary decompression after SEMS placement and
      died within 90 days. All other patients maintained stent patency at 30 days. One
      patient had asymptomatic biochemical pancreatitis, 2 patients required
      percutaneous gallbladder drainage, and 1 patient developed rigors. At 90-day
      follow-up, 1 additional patient had died with a patent stent, and 3 patients had
      occluded biliary stents. LIMITATIONS: Cohort study. CONCLUSIONS: Endobiliary RFA
      treatment appears to be safe. Randomized studies with prolonged follow-up are
      warranted.

PMID- 21184882
TI  - Unusual, large, pedunculated, polypoid lesion of the cecum.

PMID- 21184883
TI  - Ankaferd Blood Stopper in GI bleeding: alternative for everything?

PMID- 21184885
TI  - Anastomotic biliary stricture after orthotopic liver transplantation: patients'
      or endoscopists' Achilles heel?

PMID- 21184887
TI  - EUS-guided FNA of peritoneal carcinomatosis.

PMID- 21184888
TI  - Utility of colonoscopy withdrawal time measurement in the setting of an adequate
      adenoma detection rate.

PMID- 21184890
TI  - A retrograde view during colonoscopy assists detection of lesions hidden behind
      folds.

PMID- 21184891
TI  - Retroscopy increases adenoma detection rates.

PMID- 21184892
TI  - Two retroscopy studies demonstrate improved yield of adenomas.

PMID- 21184893
TI  - Retroscopy improves the detection of adenomas on the proximal aspect of colonic
      folds.

PMID- 21184894
TI  - Additional study corroborates improved adenoma detection rates for medium- and
      large-size lesions through the use of retroscopy.

PMID- 21184896
TI  - Foreword: diagnostic imaging for the general surgeon.

PMID- 21184897
TI  - Preface: diagnostic imaging for the general surgeon.

PMID- 21184898
TI  - Computed tomography, magnetic resonance, and ultrasound imaging: basic
      principles, glossary of terms, and patient safety.
AB  - The basic principles underlying computed tomography, magnetic resonance, and
      ultrasound are reviewed to promote better understanding of the properties and
      appropriate applications of these 3 common imaging modalities. A glossary of
      frequently used terms for each technique is appended for convenience. Risks to
      patient safety including contrast-induced nephropathy, radiation-induced
      malignancy, and nephrogenic systemic fibrosis are discussed.

PMID- 21184899
TI  - Imaging of the thyroid and parathyroid glands.
AB  - Current multimodal imaging techniques offer practicing providers the adequate
      framework to plan and accomplish care for patients with thyroid and parathyroid
      disorders. Available imaging modalities include ultrasonography (US), nuclear
      scintigraphy, computed tomography (CT), and magnetic resonance imaging (MRI). US
      remains the most cost-effective and the safest approach for the initial
      evaluation of the thyroid gland. Parathyroid subtraction scintigraphy provides
      localization of pathologic parathyroid glands with the greatest sensitivity.
      Localizing imaging studies allow for surgical planning with minimal risk and
      morbidity to the patient. CT scan and MRI play an adjunctive role in the further
      characterization of neck pathology.

PMID- 21184900
TI  - Contemporary breast imaging and concordance assessment: a surgical perspective.
AB  - Disease conditions of the breast are very common. Patients with such conditions
      often present to surgeons for both diagnostic evaluation and treatment. Nearly
      all of them will require breast imaging. This article summarizes the use,
      applicability, and concordance assessment of mammography, ultrasonography, and
      magnetic resonance imaging in patients who have breast complaints or
      abnormalities on clinical examination or imaging.

PMID- 21184901
TI  - Biliary, pancreatic, and hepatic imaging for the general surgeon.
AB  - Technologic advancements have allowed imaging modalities to become more useful in
      the diagnosis of hepatobiliary and pancreatic disorders. Computed tomography
      scanners now use multidetector row technology with contrast-delayed imaging for
      quicker and more accurate imaging. Magnetic resonance imaging with
      cholangiopancreatography can more clearly delineate liver lesions and the biliary
      and pancreatic ducts, and can diagnose pathologic conditions early in their
      course. Newer technologies, such as single-operator cholangioscopy and endoscopic
      ultrasonography, have sometimes shown superiority to traditional modalities. This
      article addresses the literature regarding available imaging techniques in the
      diagnosis and treatment of common surgical hepatobiliary and pancreatic diseases.

PMID- 21184902
TI  - Imaging of gastrointestinal bleeding.
AB  - Radiological techniques are important in evaluating patients with
      gastrointestinal bleeding. Scintigraphic, computed tomographic angiographic, and
      enterographic techniques are sensitive tools in identifying the source of
      bleeding and may be useful in identifying patients likely to have a benign course
      and in selecting patients for therapeutic intervention. Angiography plays a key
      role in bleeding localization, and modern embolization techniques make this a
      viable therapeutic option. With the refining developments in body imaging and
      related reconstructive techniques, it is likely that radiological interventions
      will play an expanding and critical role in evaluating patients with
      gastrointestinal hemorrhage in the future.

PMID- 21184903
TI  - Small bowel imaging.
AB  - There is a variety of options available to image the small bowel depending on the
      clinical scenario. This article describes multiple imaging options and focuses on
      several clinical scenarios common to general surgeons.

PMID- 21184904
TI  - Computed tomographic colonography.
AB  - This article provides basic information about computed tomographic colonography
      (CTC) and reviews the preparation, methods, and tools required for the procedure.
      The clinical uses for CTC (screening/diagnosis of colon cancer and colonic
      obstruction) are outlined, and its accuracy and validity are compared with other
      diagnostic methods. A summary of the benefits and risks of the test are presented
      and the current practicalities for implementation are addressed.

PMID- 21184905
TI  - Update on imaging for acute appendicitis.
AB  - Acute appendicitis is a common surgical emergency and the diagnosis can often be
      made clinically; however, many patients present with atypical findings. For these
      patients, there are multiple imaging modalities available to aid in the diagnosis
      of suspected appendicitis in an effort to avoid a negative appendectomy. Computed
      tomography is the test of choice in most patients in whom the diagnosis is not
      certain. Ultrasonography is particularly useful in children and pregnant women.
      Magnetic resonance imaging is recommended when ultrasonography is inconclusive.
      Appropriate use of these imaging studies avoids delays in treatment, prolonged
      hospitalization, and unnecessary surgery.

PMID- 21184906
TI  - Bariatric surgery and postoperative imaging.
AB  - This article reviews the use of radiological imaging in the post-gastric bypass
      patient. A thorough understanding of the reconstructed anatomy is critical to
      interpret imaging abnormalities, when present. Radiological imaging can help
      guide the surgeon's management in this specific patient population.

PMID- 21184907
TI  - The use of ultrasound in vascular procedures.
AB  - While the use of duplex ultrasound (DUS) in the diagnosis of vascular disease has
      been established, its role in vascular procedures continues to expand. More
      powerful and portable technology has helped to overcome real and perceived
      barriers to the use of DUS. Familiarity with Doppler and ultrasound physics is
      helpful to understand the potential roles and limitations of DUS. Use of real
      time imaging allows the surgeon to obtain central venous and peripheral arterial
      access, as well as place vena cava filters and treat iatrogenic arterial
      pseudoaneurysms with a greater degree of patient safety, comfort, and overall
      success.

PMID- 21184908
TI  - Computed tomography for the diagnosis and management of abdominal aortic
      aneurysms.
AB  - Computed tomography (CT) is useful in the detection and diagnosis of abdominal
      aortic aneurysms (AAA). Rupture risk can be assessed by accurately measuring
      diameter, tortuosity, thrombus extent, and wall stress. CT can aid in accurately
      determining anatomic variants as well as AAA etiology. Evaluation for surgical
      intervention is made by close examination of AAA morphology and specific anatomic
      features.

PMID- 21184909
TI  - Focused assessment with sonography for trauma: methods, accuracy, and
      indications.
AB  - Focused assessment with sonography for trauma (FAST) is an invaluable adjunct in
      the management of trauma patients for detection of free intra-abdominal and
      pericardial fluid. Over the past 2 decades, the use of this technique has
      increased significantly. This article reviews the clinical application and future
      direction of FAST.

PMID- 21184910
TI  - Imaging of the cervical spine in injured patients.
AB  - Cervical spine injury can be excluded by clinical examination, without the need
      for radiographic study, in many patients. For those who require study, computed
      tomography of the cervical spine with sagittal and coronal reconstruction is the
      best modality for both screening and diagnosing cervical spine injury. Optimal
      evaluation of the obtunded patient remains controversial.

PMID- 21184911
TI  - Imaging for blunt carotid and vertebral artery injuries.
AB  - Originally thought to be a rare occurrence, blunt cerebrovascular injuries
      (BCVIs) are now diagnosed in approximately 1% of blunt trauma patients. Early
      imaging of patients has resulted in the diagnosis of BCVIs during the
      asymptomatic phase, thus allowing prompt treatment. Although the ideal regimen of
      antithrombotic therapy has yet to be determined, treatment with either
      antiplatelet agents or anticoagulation has been shown to markedly reduce BCVI
      related stroke rate. BCVIs are rare, potentially devastating injuries;
      appropriate imaging in high-risk patients should be performed and prompt
      treatment initiated to prevent ischemic neurologic events.

PMID- 21184912
TI  - Current use of CT in the evaluation and management of injured patients.
AB  - From its beginnings as a time consuming and an inefficient imaging modality with
      no place in the evaluation of traumatically injured patients, computed axial
      tomographic (CT) scanners have evolved to yield rapid, highly sensitive images,
      revolutionizing trauma management protocols. This article describes the
      fundamentals of CT and the imaging protocols and discusses the use of CT in
      diagnosing injuries to various regions, such as abdomen, liver, spleen, pancreas,
      kidney, and chest.

PMID- 21184914
TI  - Taking the uncharted path.

PMID- 21184913
TI  - Positron emission tomography for benign and malignant disease.
AB  - Functional imaging using radiolabeled probes that specifically bind and
      accumulate in target tissues has improved the sensitivity and specificity of
      conventional imaging. Fluorodeoxyglucose (FDG)-positron emission tomography (PET)
      has shown improved diagnostic accuracy in differentiating benign from malignant
      lesions in the setting of solitary pulmonary nodules. FDG-PET has become useful
      in preoperative staging of patients with lung cancer, and is being tested with
      many other malignancies for its ability to change patient management. This
      article provides an overview of the current status of FDG-PET and presents the
      challenges of moving toward routine use.

PMID- 21184915
TI  - Quiz page January 2011. A kidney transplant patient with rapidly progressive
      kidney failure and a radiopaque pyelum wall.

PMID- 21184916
TI  - What to measure-albuminuria or total proteinuria?

PMID- 21184917
TI  - Fistula first: recent progress and ongoing challenges.

PMID- 21184918
TI  - Validity of administrative database coding for kidney disease: a systematic
      review.
AB  - BACKGROUND: Information in health administrative databases increasingly guides
      renal care and policy. STUDY DESIGN: Systematic review of observational studies.
      SETTING & POPULATION: Studies describing the validity of codes for acute kidney
      injury (AKI) and chronic kidney disease (CKD) in administrative databases
      operating in any jurisdiction. SELECTION CRITERIA: After searching 13 medical
      databases, we included observational studies published from database inception
      though June 2009 that validated renal diagnostic and procedural codes for AKI or
      CKD against a reference standard. INDEX TESTS: Renal diagnostic or procedural
      administrative data codes. REFERENCE TESTS: Patient chart review, laboratory
      values, or data from a high-quality patient registry. RESULTS: 25 studies of 13
      databases in 4 countries were included. Validation of diagnostic and procedural
      codes for AKI was present in 9 studies, and validation for CKD was present in 19
      studies. Sensitivity varied across studies and generally was poor (AKI median,
      29%; range, 15%-81%; CKD median, 41%; range, 3%-88%). Positive predictive values
      often were reasonable, but results also were variable (AKI median, 67%; range,
      15%-96%; CKD median, 78%; range, 29%-100%). Defining AKI and CKD by only the use
      of dialysis generally resulted in better code validity. The study characteristic
      associated with sensitivity in multivariable meta-regression was whether the
      reference standard used laboratory values (P < 0.001); sensitivity was 39% lower
      when laboratory values were used (95% CI, 23%-56%). LIMITATIONS: Missing data in
      primary studies limited some of the analyses that could be done. CONCLUSIONS:
      Administrative database analyses have utility, but must be conducted and
      interpreted judiciously to avoid bias arising from poor code validity.

PMID- 21184921
TI  - Kidney paired donation: fundamentals, limitations, and expansions.
AB  - Incompatibility between the candidate recipient and the prospective donor is a
      major obstacle to living donor kidney transplant. Kidney paired donation (KPD)
      can circumvent the incompatibility by matching them to another candidate and
      living donor for an exchange of transplants such that both transplants are
      compatible. KPD has faced legal, logistical, and ethical challenges since its
      inception in the 1980s. Although the full potential of this modality for
      facilitating transplant for individuals with incompatible donors is unrealized,
      great strides have been made. In this review article, we detail how several
      impediments to KPD have been overcome to the benefit of ever greater numbers of
      patients. Limitations and questions that have been addressed include blood group
      type O imbalance, reciprocal match requirements, simultaneous donor nephrectomy
      requirements, combining KPD with desensitization, the role of list-paired
      donation, geographic barriers, legal barriers, concerns regarding living donor
      safety, fragmented registries, and inefficient matching algorithms.

PMID- 21184920
TI  - Novel equations to estimate lean body mass in maintenance hemodialysis patients.
AB  - BACKGROUND: Lean body mass (LBM) is an important nutritional measure representing
      muscle mass and somatic protein in hemodialysis patients, for whom we developed
      and tested equations to estimate LBM. STUDY DESIGN: A study of diagnostic test
      accuracy. SETTING & PARTICIPANTS: The development cohort included 118
      hemodialysis patients with LBM measured using dual-energy x-ray absorptiometry
      (DEXA) and near-infrared (NIR) interactance. The validation cohort included 612
      additional hemodialysis patients with LBM measured using a portable NIR
      interactance technique during hemodialysis. INDEX TESTS: 3-month averaged serum
      concentrations of creatinine, albumin, and prealbumin; normalized protein
      nitrogen appearance; midarm muscle circumference (MAMC); handgrip strength; and
      subjective global assessment of nutrition. REFERENCE TEST: LBM measured using
      DEXA in the development cohort and NIR interactance in validation cohorts.
      RESULTS: In the development cohort, DEXA and NIR interactance correlated strongly
      (r = 0.94, P < 0.001). DEXA-measured LBM correlated with serum creatinine level,
      MAMC, and handgrip strength, but not with other nutritional markers. Three
      regression equations to estimate DEXA-measured LBM were developed based on each
      of these 3 surrogates and sex, height, weight, and age (and urea reduction ratio
      for the serum creatinine regression). In the validation cohort, the validity of
      the equations was tested against the NIR interactance-measured LBM. The equation
      estimates correlated well with NIR interactance-measured LBM (R2 >= 0.88),
      although in higher LBM ranges, they tended to underestimate it. Median (95%
      confidence interval) differences and interquartile range for differences between
      equation estimates and NIR interactance-measured LBM were 3.4 (-3.2 to 12.0) and
      3.0 (1.1-5.1) kg for serum creatinine and 4.0 (-2.6 to 13.6) and 3.7 (1.3-6.0) kg
      for MAMC, respectively. LIMITATIONS: DEXA measurements were obtained on a
      nondialysis day, whereas NIR interactance was performed during hemodialysis
      treatment, with the likelihood of confounding by volume status variations.
      CONCLUSIONS: Compared with reference measures of LBM, equations using serum
      creatinine level, MAMC, or handgrip strength and demographic variables can
      estimate LBM accurately in long-term hemodialysis patients.

PMID- 21184922
TI  - Intra-abdominal Hypertension and Abdominal Compartment Syndrome.
AB  - Increased intra-abdominal pressure (IAP), also referred to as intra-abdominal
      hypertension (IAH), affects organ function in critically ill patients and may
      lead to abdominal compartment syndrome (ACS). Although initially described in
      surgical patients, IAH and ACS also occur in medical patients without abdominal
      conditions. IAP can be measured easily and reliably in patients through the
      bladder using simple tools. The effects of increased IAP are multiple, but the
      kidney is especially vulnerable to increased IAP because of its anatomic
      position. Although the means by which kidney function is impaired in patients
      with ACS is incompletely elucidated, available evidence suggests that the most
      important factor involves alterations in renal blood flow. IAH should be
      considered as a potential cause of acute kidney injury in critically ill
      patients; its role in other conditions, such as hepatorenal syndrome, remains to
      be elucidated. Because several treatment options (both medical and surgical) are
      available, IAH and ACS should no longer be considered irrelevant epiphenomena of
      severe illness or critical care. An integrated approach targeting IAH may improve
      outcomes and decrease hospital costs, and IAP monitoring is a first step toward
      dedicated IAH management. IAH prevention, most importantly during abdominal
      surgery but also during fluid resuscitation, may avoid ACS altogether. However,
      when ACS occurs and medical treatment fails, decompressive laparotomy is the only
      option.

PMID- 21184923
TI  - Asymptomatic large extracapsular renal pseudoaneurysm following kidney transplant
      biopsy.
AB  - Vascular complications after kidney biopsy include hematomas, arteriovenous
      fistulas, and pseudoaneurysms. Ultrasonography is a useful tool for the diagnosis
      of these complications, and color Doppler scan is effective at distinguishing
      among them. We describe a transplant patient who underwent percutaneous kidney
      biopsy in whom echography performed after biopsy showed a pulsatile hypoechoic
      perinephric mass of 4.4 cm. This collection illuminated with color Doppler and
      connected to the transplant. Color Doppler scanning of the mass showed high
      velocity turbulent flow within the cavity and a jet of blood from an intrarenal
      segmental artery. A typical pattern biphasic flow ("to-and-fro" waveform) at the
      pseudoaneurysm neck on color Doppler confirmed the diagnosis of postbiopsy
      pseudoaneurysm. Pseudoaneurysms usually are asymptomatic, but when they cause
      clinical signs or risk rupture, interventional treatment is required.
      Supraselective coil embolization of the artery feeding the pseudoaneurysm was
      performed successfully in our patient. Pseudoaneurysm can mimic renal cysts on
      gray-scale ultrasound. We suggest that Doppler sonography be performed in cystic
      areas detected after biopsy to exclude pseudoaneurysm.

PMID- 21184919
TI  - Baseline physical performance, health, and functioning of participants in the
      Frequent Hemodialysis Network (FHN) trial.
AB  - BACKGROUND: Self-reported physical health and functioning and direct measures of
      physical performance are decreased in hemodialysis patients and are associated
      with mortality and hospitalization. STUDY DESIGN: We determined baseline cross
      sectional associations of physical performance, health, and functioning with
      demographics, clinical characteristics, nutritional indexes, laboratory
      benchmarks, and measures of body composition in participants in the Frequent
      Hemodialysis Network (FHN) trial. SETTING & PARTICIPANTS: 375 persons enrolled in
      the FHN with data for physical performance, health, and functioning. PREDICTORS:
      Explanatory variables were categorized into fixed factors of age, race, comorbid
      conditions (diabetes mellitus, heart failure, and peripheral arterial disease)
      and potentially modifiable factors of dialysis dose, phosphorus level, hemoglobin
      level, equilibrated normalized protein catabolic rate (enPCR), body composition,
      body mass index, phase angle, and ratio of intracellular water volume to body
      weight (calculated from bioelectrical impedance). OUTCOMES: Scores on tests of
      physical performance, health, and functioning. MEASUREMENTS: Physical performance
      measured using the Short Physical Performance Battery, self-reported physical
      health and functioning using the 36-Item Short Form Health Survey (SF-36). Body
      composition (body mass index and bioimpedance analysis) and laboratory data were
      obtained from affiliated dialysis providers. RESULTS: Relative to population
      norms, scores for all 3 physicality metrics were low. Poorer scores on all 3
      metrics were associated with diabetes mellitus and peripheral arterial disease.
      Poorer scores on the SF-36 Physical Functioning subscale and Short Physical
      Performance Battery also were associated with age, lower ratio of intracellular
      water volume to body weight, and lower enPCR. Black race was associated with
      poorer scores on the Short Physical Performance Battery. LIMITATIONS: This was a
      cross-sectional study of individuals agreeing to participate in the FHN study and
      may not be generalizable to the general dialysis population. CONCLUSIONS:
      Hemodialysis patients show markedly impaired physical performance, health, and
      functioning relative to population norms. Although some factors associated with
      these impairments are not modifiable, others may change with improvement in
      nutritional status or body composition.

PMID- 21184925
TI  - Residual kidney function and quality of life in incident hemodialysis patients.

PMID- 21184927
TI  - Measured GFR has limited clinical utility.

PMID- 21184930
TI  - Invited commentary.

PMID- 21184928
TI  - US Renal Data System 2010 Annual Data Report.

PMID- 21184931
TI  - Perioperative cardiac events in endovascular repair of complex aortic aneurysms
      and association with preoperative studies.
AB  - BACKGROUND: Endovascular repair of complex aortic aneurysms (CAAs) can be
      performed in high-risk individuals, yet is still associated with significant
      morbidity, including spinal cord ischemia, cardiac complications, and death. This
      analysis was undertaken to better define the cardiac risk for CAA. METHODS: A
      prospective database of patients undergoing thoracoabdominal or juxtarenal aortic
      aneurysm repair with branched and fenestrated endografts was used to
      retrospectively determine the number of cardiac events, defined as myocardial
      infarction (MI), atrial fibrillation (AF), and ventricular arrhythmia (VA), that
      occurred <= 30 days of surgery. Postoperative serial troponin measurements were
      performed in 266 patients. Any additional available cardiac information,
      including preoperative echocardiography, physiologic stress tests, and history of
      cardiac disease, was obtained from medical records. The efficacy of preoperative
      stress testing and the association of various echo parameters were evaluated in
      the context of cardiac outcomes using univariable and multivariable logistic
      regression models. RESULTS: Between August 2001 and December 2007, 395 patients
      underwent endovascular repair of a thoracoabdominal or juxtarenal aortic
      aneurysm. The incidence of AF, VA, and 30-day cardiac-related death was 9%, 3%,
      and 2%, respectively. Overall 30-day mortality was 6%. Univariable analysis
      showed the presence of mitral annulus calcification was associated with MI (odds
      ratio [OR], 3.5; 95% confidence interval [CI], 0.9-13.8; P = .07). Left atrium
      cavity area, ejection fraction, left ventricle mass, and left ventricular mass
      index were univariably associated with the presence of VA. Multivariable analysis
      showed only the left atrium cavity area was independently associated with VA (OR,
      1.2; 95% CI, 1.0-1.5; P = .07). Stress test was done in 179 patients. Negative
      stress test results occurred in 152 (85%), of whom 9 (6%) sustained an MI during
      the 30-day perioperative course. MI occurred in 2 of the 27 patients (7%) who had
      a positive stress test result. CONCLUSIONS: Endovascular repair of CAA can be
      performed in high-risk individuals but is associated with significant cardiac
      risk. It remains difficult to risk stratify patients using preoperative stress
      testing. Echo evaluation may help to identify patients who may be more likely to
      develop ventricular arrhythmias in the postoperative period and thus warrant
      closer monitoring. Postoperative troponin monitoring of all patients undergoing
      repair of CAA is warranted given the overall risk of MI.

PMID- 21184934
TI  - Invited commentary.

PMID- 21184932
TI  - In situ rifampin-soaked grafts with omental coverage and antibiotic suppression
      are durable with low reinfection rates in patients with aortic graft enteric
      erosion or fistula.
AB  - OBJECTIVE: We previously reported that in situ rifampin-soaked grafts (ISRGs)
      were safe in select patients with aortic graft infections, with the best results
      in those with aortic graft enteric erosion or fistula (AGEF). This study
      evaluates the late results of ISRG for AGEF. METHODS: From 1990 to 2008, 183
      patients were treated for aortic graft infections (121 primary and 62 AGEF). We
      reviewed 54 patients treated for AGEF with a standard protocol, which included
      excision of the infected part of the graft, intestinal repair, ISRG with omental
      wrap, and long-term antibiotics. We excluded 8 patients with AGEF (13%) treated
      with axillofemoral grafts (AXFG, n = 5) or in situ femoral vein (n = 3) due to
      excessive perigraft purulence. Endpoints were early morbidity and mortality, late
      survival, reinfection, and graft-related complications. RESULTS: There were 45
      male patients and 9 female patients with a mean age of 69 +/- 9 years.
      Presentation was gastrointestinal bleeding in 33 patients, fever in 25 patients,
      and hemorrhagic shock in 10 patients. Other features were perigraft fluid in 29
      patients and purulence in 9 patients. Forty-two patients (80%) had infections
      isolated to a portion of the graft body or limb, with the remainder of the graft
      well incorporated. Total graft excision was performed in 31 patients and partial
      excision in 23 patients. Total operating time was 6.2 +/- 1.9 hours.
      Postoperative complications occurred in 28 patients (52%), and there were 5
      deaths (9%). Operative mortality was 2.3% in stable patients (1 of 44) and 40% in
      those with hemorrhagic shock (4 of 10; P < .001). The hospital stay was 20 +/- 18
      days. Mean follow-up was 51 months (range, 3-197 months). Five-year patient
      survival, primary graft patency, and limb salvage rates were 59 +/- 8%, 92 +/-
      5%, and 100%, respectively. There were no late graft-related deaths. There were
      two (4%) graft reinfections, one that was treated with axillofemoral bypass, and
      the other with perigraft fluid aspiration and oral antibiotic suppression.
      CONCLUSION: ISRGs with omental wrap and long-term antibiotics are associated with
      low reinfection rates in patients with AGEF who do not have excessive perigraft
      purulence. Graft patency and limb salvage rates are excellent.

PMID- 21184935
TI  - Endovascular management of superior mesenteric artery pseudoaneurysm.
AB  - A 31-year-old man underwent a Whipple procedure for a pancreatic neuroendocrine
      tumor, which consists of a pancreaticoduodenectomy and reconstruction to restore
      intestinal continuity. Six weeks after the operation, he presented with severe
      mid-epigastric pain radiating to his back. Imaging studies revealed a large
      pseudoaneurysm arising from the superior mesenteric artery. Selective superior
      mesenteric angiography confirmed the presence of the pseudoaneurysm. A 6 mm * 2.5
      cm stent graft (Viabhan; W.L. Gore, Flagstaff, Ariz) was deployed across the
      pseudoaneurysm origin with preservation of the mesenteric branches. The patient
      had immediate resolution of symptoms and follow-up imaging showed patency of the
      stent graft and exclusion of the pseudoaneurysm.

PMID- 21184936
TI  - The PARTNER trial.

PMID- 21184938
TI  - Regarding "gender trends in the repair of ruptured abdominal aortic aneurysms and
      outcomes".

PMID- 21184939
TI  - Regarding "clinical course of asymptomatic patients with carotid duplex scan end
      diastolic velocities of 100 to 124 centimeters per second".

PMID- 21184942
TI  - Regarding "analysis of risk factors for abdominal aortic aneurysm in a cohort of
      more than 3 million individuals".

PMID- 21184945
TI  - Regarding "asymptomatic carotid artery stenosis-Medical therapy alone versus
      medical therapy plus carotid endarterectomy or stenting".

PMID- 21184946
TI  - Regarding "haptoglobin 2-1 phenotype predicts rapid growth of abdominal aortic
      aneurysms".

PMID- 21184949
TI  - Near miss maternal mortality in a multiethnic population.
AB  - PURPOSE: To determine the impact of ethnicity on "near miss"/severe obstetric
      morbidity in a multi-ethnic, tertiary care population. METHODS: We carried out a
      cross-sectional analysis using birth data for 12,774 women with Medicaid who gave
      birth between January 1994 and January 2005 at Duke University. Univariate and
      multivariate analyses were carried out to compare ethnic groups and risk factors
      for severe obstetric morbidity and mortality using codes for conditions
      corresponding to the WHO definitions of near miss maternal morbidities. RESULTS:
      African-American women experienced significantly more pregnancy complications
      (25.4%) compared to White (21.7%) and Hispanic (18.8%) women. The presence of
      medical comorbidities was highest among African-Americans (9.1%) compared to
      Whites (8.1%) and Hispanics (2.6%). Near miss mortality, however, was
      significantly higher in Hispanic women (5.9%) compared to African-Americans
      (4.6%), and Whites (4.1%). Hispanic women had 45% greater risk of near miss
      mortality compared to Whites (relative risk [RR] = 1.45, 95% confidence interval
      [CI]: 1.14-1.84) whereas differences were non-significant for African-American
      women. In multivariate regression, near misses remained highest for Hispanic
      women (RR = 1.66; 95% CI: 1.27-2.17). CONCLUSIONS: The increase in near miss
      maternal mortality for Hispanic women suggests a more complex interaction between
      ethnicity, socioeconomic status and health than traditional birth outcome
      measures capture.

PMID- 21184950
TI  - Clustering of obesity-related risk behaviors in children and their mothers.
AB  - PURPOSE: To examine the clustering and patterns of obesity-related behaviors in
      children and their mothers and the concordance between mother and child pairs.
      METHODS: Primary school-aged children and their mothers in Victoria, Australia,
      participated (data from 549 mothers, 352 children, and 304 mother/child pairs).
      Examination of behavior patterns included 1) assessment of the overlap in
      national physical activity, screen-time, and fruit and vegetable consumption
      guidelines being met; and 2) cluster analysis of positive (consumption of fruits
      and vegetables) and negative (consumption of energy dense food/drink) dietary
      behaviors, sedentary behavior/screen-time, and physical activity. RESULTS: Only
      partial overlap was observed between groups meeting national recommendations for
      sedentary behavior and consumption of fruit and vegetables and energy-dense food.
      Less than 40% of mothers and children were meeting sedentary behavior guidelines.
      In both mothers and children five clusters were identified. With the exception of
      a single cluster in children with high levels of physical activity, clusters of
      healthy and unhealthy behavior were concordant in mothers and their children (p <
      .0001), particularly those defined by sedentary behaviors and consumption of
      energy-dense food/drink. CONCLUSIONS: Complex patterns of obesity-related
      behaviors exist in children and their mothers. The concordance of clusters
      between children and their mothers suggests that modeling of sedentary behavior
      and creation of a child's eating environment by parents may be particularly
      important influences on children's behavior.

PMID- 21184951
TI  - Life course origins of the metabolic syndrome in middle-aged women and men: the
      role of socioeconomic status and metabolic risk factors in adolescence and early
      adulthood.
AB  - PURPOSE: To assess whether body mass index (BMI), blood pressure, and
      socioeconomic status in adolescence and early adulthood are independently related
      to the metabolic syndrome in adult women and men. METHODS: We based our work on a
      Swedish prospective cohort study that recruited participants at 16 years of age
      (N = 1083 at age 16; 403 women and 429 men at age 43, 78% of those still alive [N
      = 1071]). Blood pressure (BP) and BMI were assessed when participants were 16 and
      21 years of age. At age 43, the metabolic syndrome was defined according to the
      International Diabetes Federation guidelines. Socioeconomic status (SES) was
      operationalized by the participant (age 21 and 43) or parent's (age 16)
      occupational status. Information on smoking, snuff, alcohol, and inactivity was
      collected at age 43. RESULTS: In women, SES at age 16 was independently related
      to the risk of metabolic syndrome. In women and men, BMI at age 16 was related to
      metabolic syndrome but was attenuated by BMI at age 21, which was significant in
      the final model; in women systolic BP displayed similar patterns. CONCLUSIONS:
      Our data seem to suggest two independent life course pathways for metabolic
      syndrome: one metabolic pathway for both women and men operating through BMI (for
      women also systolic BP) in adolescence and early adulthood, and for women, an
      apparently independent pathway through adolescent socioeconomic disadvantage.

PMID- 21184952
TI  - Low high density lipoprotein cholesterol: prevalence and associated risk-factors
      in a large French population.
AB  - PURPOSE: High density lipoprotein-cholesterol (HDL-C) is a strong predictor of
      cardiovascular risk. We investigated the distribution of HDL-C in a French
      general population according to age, sex, and the risk factors associated with
      low HDL-C values. METHODS: A group of 18,483 men and 22,047 women 16-79 years of
      age were investigated during a medical check-up. Relevant parameters were studied
      in three groups according to age and gender-specific percentile classes (<=5th
      [HDL5] median and >95th). Gender-specific logistic regression models selected
      variables associated with HDL5. RESULTS: Using the National Cholesterol Education
      Program Adult Treatment Panel III criteria (threshold: 40 mg/dL in men, 50 mg/dL
      in women) the prevalence of low HDL-C was 11.1% and 26.4% in men and women and it
      decreased with age. Mean HDL-C levels increased with age. HDL5 was positively
      associated with a sedentary lifestyle and deprivation (p < 0.00001) even after
      adjustment on alcohol consumption and smoking. Abdominal obesity, smoking,
      hypertriglyceridemia, hyperleucocytosis, and low alcohol consumption were
      associated with HDL5 for both genders. CONCLUSIONS: The prevalence of low HDL-C
      was similar to that observed in other Europeans but lower than in the United
      States. HDL5 was associated with cardiovascular risk factors, metabolic syndrome,
      and social deprivation. A prevention policy to increase HDL-C levels should focus
      on reducing smoking and abdominal obesity, particularly in deprived subjects.

PMID- 21184953
TI  - The association between blood pressure and years of schooling versus educational
      credentials: test of the sheepskin effect.
AB  - PURPOSE: Attaining a degree may offer greater opportunities for health than years
      of schooling alone. This study examines whether there is a degree, or
      "sheepskin," effect on the association between education and blood pressure.
      METHODS: Multivariable-adjusted ordinal and linear regression models assessed
      associations of years of schooling and degree attainment with systolic and
      diastolic blood pressure in a sample of 552 adults ages 38 to 47 years. RESULTS:
      Years of schooling was inversely associated with systolic blood pressure
      adjusting for age, gender and race (beta = -0.4, 95% confidence limit: -0.7, -0.1
      mmHg systolic blood pressure/year of schooling). Additional adjustment for
      mother's education, childhood verbal intelligence quotient, childhood health, and
      childhood socioeconomic status had minimal impact on effect size (beta = -0.3,
      95% confidence limit = -0.7, 0.0). However, years of schooling was no longer
      associated with blood pressure in the fully adjusted model which included
      additional adjustment for degree attained (beta = 0.0, 95% confidence limit: 
      0.5, 0.4). In the fully adjusted model (including adjustment for years of
      schooling), individuals with a graduate degree still had significantly lower
      systolic blood pressure than HS degree-holders (e.g., beta = -9.2, 95% confidence
      limit: -15.2, -3.2 for graduate vs high school degree). Findings were similar for
      diastolic blood pressure. CONCLUSIONS: The association of years of schooling with
      blood pressure may be largely due to degree attainment rather than simply the
      knowledge and skills accumulated due to years of schooling alone.

PMID- 21184954
TI  - Single-incision laparoscopic staging for endometrial cancer.

PMID- 21184955
TI  - Comparison of hospital performance in emergency versus elective general surgery
      operations at 198 hospitals.
AB  - BACKGROUND: Surgical quality improvement has focused on elective general surgery
      (ELGS) outcomes despite the substantial risk associated with emergency general
      surgery (EMGS) procedures. Furthermore, any differences in the quality of care
      provided to EMGS versus ELGS patients are not well described. We compared risk
      factors and risk-adjusted outcomes associated with EMGS and ELGS procedures to
      assess whether hospitals have comparable outcomes across these procedures. STUDY
      DESIGN: Using American College of Surgeons National Surgical Quality Improvement
      Program data (2005 to 2008), regression models were constructed for 30-day
      overall morbidity, serious morbidity, and mortality among all patients, EMGS
      patients, and ELGS patients. Observed-to-expected (O/E) ratios were calculated
      from models based on EMGS or ELGS patients. Association of hospital performance
      after EMGS versus ELGS procedures was assessed by evaluating correlations of O/E
      ratios; agreement in outlier status (hospitals where O/E confidence intervals
      [CI] do not overlap 1.0) was evaluated with weighted kappa. RESULTS: Of 473,619
      procedures, 67,445 (14.2%) patients underwent an EMGS procedure. EMGS patients
      were more likely to experience any morbidity (odds ratio [OR] 1.20; 95% CI 1.16
      to 1.23), serious morbidity (OR 1.26; 95% CI 1.21 to 1.30), and mortality (OR
      1.39; 95% CI 1.30 to 1.48). Correlation between O/E ratios for EMGS and ELGS were
      moderate to low (overall morbidity = 0.48, p < 0.0001; serious morbidity = 0.41,
      p < 0.0001, mortality = 0.18, p = 0.01). Outlier status was not consistent across
      EMGS and ELGS, with only slight agreement (overall morbidity = 0.18, p < 0.0001;
      serious morbidity = 0.16, p = 0.001, mortality = 0.19, p = 0.01). CONCLUSIONS:
      EMGS patients are at substantially greater risk than ELGS patients for adverse
      events. Hospitals do not appear to have highly consistent performance across EMGS
      and ELGS outcomes. Processes of care that afford improved outcomes to EMGS
      patients need to be identified and disseminated.

PMID- 21184956
TI  - Magnamosis II: Magnetic compression anastomosis for minimally invasive
      gastrojejunostomy and jejunojejunostomy.
AB  - BACKGROUND: Previously we demonstrated the safety and patency of a magnetic
      compression anastomosis (magnamosis). We present the further development of this
      technique, with specific focus on optimizing device design for minimally invasive
      magnamosis. STUDY DESIGN: The magnamosis device was designed to incorporate 3
      features: 2 convex-concave radially symmetric halves that magnetically self
      align, a central channel for immediate patency, and specially engineered radial
      topography of the mating surfaces to promote gradual remodeling. Each symmetrical
      half consists of a ring-shaped neodymium-iron-boron magnet encased in
      polycarbonate casing. Twenty-one young adult pigs underwent either magnetic
      gastrojejunostomy (n = 13) or jejunojejunostomy (n = 8). Animals were euthanized
      at 1, 2, 4, and 6 weeks after operation. Anastomoses were studied with contrast
      radiography, burst pressure, and histology. RESULTS: Gastrojejunostomy: In all
      animals with successful placement of magnets, anastomoses were patent by contrast
      fluoroscopy, well healed by histologic examination, and showed excellent burst
      strength. Jejunojejunostomy: All animals had uneventful clinical courses,
      indicating that the magnamosis with immediate patency functioned properly without
      device dislodgement. At sacrifice, all magnamoses were patent, well healed by
      histology, and had burst strengths that equaled or exceeded that of traditional
      stapled anastomoses. CONCLUSIONS: Minimally invasive placement of a custom
      magnetic device in the stomach and jejunum allows intraluminal self-alignment and
      subsequent compression anastomosis over 3 to 10 days. The magnamosis is
      immediately patent and develops strength equal to or greater than that of hand
      sewn or stapled anastomoses. Magnamosis is effective in the pig model, and may be
      a safe, effective, and minimally invasive alternative to current anastomotic
      strategies in humans.

PMID- 21184957
TI  - The impact of select chronic diseases on outcomes after trauma: a study from the
      National Trauma Data Bank.
AB  - BACKGROUND: Data regarding pre-existing comorbidities is often poorly recorded in
      trauma registries, and reports of their impact on outcomes are conflicting.
      Additionally, many previous reports, when conducting data analysis, do not
      reliably account for differences in case and control cohorts. Our objective was
      to identify a subset of patients with reliable comorbidity and complication data
      in the National Trauma Data Bank (NTDB) in order to determine the impact of
      select chronic organ system dysfunction on morbidity and mortality using case
      control methodology. STUDY DESIGN: We analyzed a refined dataset from NTDB 7.1
      (2002 to 2006) containing admissions to Level 1 and 2 trauma centers, which
      specified using chart abstraction to document comorbidities and complications.
      Patients with a history of cirrhosis, dialysis, HIV, and warfarin therapy were
      compared with a 2:1 case-matched control group. Data regarding age; Injury
      Severity Score (ISS); ventilator, ICU, and hospital lengths of stay;
      complications; and mortality were obtained. Pearson's chi-square, Fisher's exact
      test, and the t-test were used to compare demographics and outcomes of each
      comorbidity group. A p value < 0.05 was considered significant. RESULTS: After
      case-control matching, pre-existing cirrhosis, dialysis, and warfarin therapy
      were found to be risk factors for both complications and mortality; HIV/AIDS was
      found to be a risk factor only for complications. CONCLUSIONS: Chronic hepatic
      failure, end-stage renal disease, immunodeficiency, and acquired coagulopathy are
      associated with higher resource use, complication rates, and mortality in a
      refined subset of NTDB patients.

PMID- 21184959
TI  - Challenges of improving outcomes of rectal cancer surgery in obese patients.

PMID- 21184960
TI  - Understanding racial disparities in cancer treatment and outcomes.

PMID- 21184962
TI  - Dichotomizing continuous prognostic factors can cause paradoxical results in
      survival models.

PMID- 21184963
TI  - No small issue: Hepatectomies-minimally invasive but more-than-minimally biased
      toward minor resections?

PMID- 21184966
TI  - The relationship between obesity and psychiatric disorders across ethnic and
      racial minority groups in the United States.
AB  - CONTEXT: Epidemiologic studies of obesity have not examined the prevalence and
      relationship of mental health conditions with obesity for diverse ethnic and
      racial populations in the United States. OBJECTIVE: (1) To assess whether obesity
      was associated with diverse psychiatric diagnoses across a representative sample
      of non-Latino whites, Latinos, Asians, African-Americans, and Afro-Caribbeans;
      and (2) to test whether physical health status, smoking, sociodemographic
      characteristics, and psychiatric comorbidities mediate any of the observed
      associations. DESIGN: Our analyses used pooled data from the NIMH Collaborative
      Psychiatric Epidemiology Surveys (CPES). Analyses tested the association between
      obesity and psychiatric disorders in a diverse sample of Americans (N=13,837),
      while adjusting for factors such as other disorders, age, gender, socioeconomic
      status, smoking and physical health status (as measured by chronic conditions and
      WHO-DAS scores) in different models. RESULTS: The relationship between obesity
      and last-year psychiatric disorders varied by ethnicity/race. The likelihood of
      having mood or anxiety disorder was positively associated with obesity for
      certain racial/ethnic groups, but was moderated by differences in physical health
      status. Substance-use disorders were associated with decreased odds for obesity
      in African-Americans. CONCLUSIONS: The role of physical health status (as
      measured by chronic conditions and WHO-DAS scores) dramatically changes the
      pattern of associations between obesity and psychiatric disorders, suggesting the
      important role it plays in explaining differential patterns of association across
      racial and ethnic groups.

PMID- 21184967
TI  - Response style and vulnerability to anger-induced eating in obese adults.
AB  - Emotional eating appears to contribute to weight gain, but the characteristics
      that make one vulnerable to emotional eating remain unclear. The present study
      examined whether two negative affect response styles, rumination and distraction,
      influenced palatable food intake following an anger mood induction in normal
      weight and obese adults. We hypothesized that higher rumination and lower
      distraction would be associated with greater vulnerability to anger-induced
      eating, particularly among obese individuals. Sixty-one participants (74% female,
      mean age=34.6) underwent neutral and anger mood inductions in counterbalanced
      order. Directly following each mood induction, participants were provided with
      2400 kcal of highly palatable snack foods in the context of a laboratory taste
      test. Results revealed that distraction influenced energy intake following the
      mood induction for obese but not normal weight individuals. Obese participants
      who reported greater use of distraction strategies consumed fewer calories than
      those reporting less use of distraction strategies. These findings were
      independent of subjective hunger levels, individual differences in mood responses
      and trait anger, and other factors. Rumination did not account for changes in
      energy intake among obese or normal weight participants. Among obese individuals,
      the tendency to utilize fewer negative affect distraction strategies appears to
      be associated with vulnerability to eating in response to anger. Future research
      should determine whether coping skills training can reduce emotional eating
      tendencies.

PMID- 21184968
TI  - Self-reported vs. actual energy intake in youth with and without loss of control
      eating.
AB  - Episodes of loss of control over eating (LOC) in children and adolescents--often
      characterized by the consumption of highly palatable dessert and snack-type foods
      -have been associated with a lack of awareness while eating that could lead to
      under- or over-estimation of how much food is consumed. However, little is known
      about the reporting accuracy of food intake in youth with and without LOC eating.
      One hundred fifty-six girls and boys were administered the Eating Disorder
      Examination to assess for the presence of LOC eating. Youth were queried
      regarding the amounts of foods consumed directly following a multi-item,
      laboratory buffet test meal. Children with LOC (n=42) did not differ
      significantly from youth without LOC (n=114) in reporting accuracy of total food
      intake (reported minus actual energy intake: 153.0 +/- 59.6 vs. 96.9 +/- 36.0
      kcal; p=0.42). However, compared to those without LOC, children with LOC were
      less accurate at reporting percentage of energy intake from carbohydrate
      (p=0.01). Youth with LOC were also less accurate at reporting their intake of
      desserts (p=0.04). Findings point to the possibility that youth with LOC may have
      poorer recall of sweet food consumption. Future research is required to examine
      whether poorer recall reflects a lack of awareness while eating palatable, sweet
      foods.

PMID- 21184969
TI  - Coping and social support as potential moderators of the relation between anxiety
      and eating disorder symptomatology.
AB  - Trait anxiety and eating disorder (ED) symptomatology are often thought to be
      inextricably linked. Because anxiety often precedes an ED, predicts poor outcome,
      and persists even after recovery from an ED, it is important to examine whether
      certain factors have the ability to potentially attenuate anxiety's effect on
      eating pathology. In the current study, we examined two possible moderating
      factors: coping skills and social support. Participants were 96 females seen at
      one point for an ED at a Midwestern clinic, including 53 with a current ED
      diagnosis and 43 who no longer met criteria for an ED and who were at varying
      levels of recovery. Results revealed that emotion-oriented coping moderated the
      relation between anxiety and ED symptoms. Individuals who were high in trait
      anxiety and who reported low levels of emotion-oriented coping reported much
      lower levels of ED symptomatology than those with high trait anxiety and high
      emotion-oriented coping. Contrary to our hypotheses, task-oriented coping,
      avoidance-oriented coping, and perceived social support (total, family, friend,
      and special person) did not emerge as moderators of the relation between trait
      anxiety and eating pathology. Results provide growing support that factors that
      interact with anxiety can lessen anxiety's effect on eating pathology.
      Implications for treatment and future directions are discussed.

PMID- 21184970
TI  - Race, weight, and correlates of binge eating in female college students.
AB  - This study examined the correlates of race, weight status, and binge eating among
      715 female undergraduate students (77% Caucasian; 13% African American) enrolled
      at an urban university. Approximately 21.7% of Caucasians and 36.8% of African
      Americans (AA) were overweight/obese. Higher BMI was associated with BED, and
      severity of binge eating symptoms. After removing participants who endorsed
      compensatory behaviors >= 1*/week from the analyses, 8.4% of the sample met
      criteria for BED (2.4% of the AA and 9.9% of the Caucasian students) and 44%
      reported severe binge eating symptoms. AA students were less likely to have BED
      than Caucasian students and reported less severe binge eating symptomatology. For
      Caucasian students, mood, cognitive restraint, drive for thinness, and BMI all
      contributed significant individual variance in binge eating severity. For African
      Americans, mood, body image dissatisfaction, and drive for thinness were found to
      be unique contributors. For those meeting criteria for BED, retrospectively
      recalled predictors of binge eating included negative affect (e.g., self-anger,
      worry, guilt), but not hunger. Behavioral triggers for binge behavior differed by
      race, as well, with African American students retrospectively reporting lower
      levels of anxiety prior to bingeing. Results from this study suggest that there
      are racial differences in binge eating behaviors. Future studies are needed to
      examine differences in eating practices among racial groups (e.g., grazing, large
      portions, high fat food preparation) that may contribute to early onset weight
      gain and obesity. The results suggest the importance of sensitive tailored weight
      and disordered eating interventions for college women from diverse backgrounds.

PMID- 21184972
TI  - The impact of perceived social support and negative life events on bulimic
      symptoms.
AB  - OBJECTIVE: The purpose of the current study was to evaluate the relationship
      between social support, negative life events, and disordered eating using a
      longitudinal design. More specifically, we examined whether the interaction
      between perceived social support and occurrence of negative life events would
      predict symptoms of eating disorders. METHOD: Two hundred seventy female
      undergraduate students completed self-report questionnaires at two time points to
      assess perceived social support, negative life events experienced, and current
      psychopathology. RESULTS: Low social support and a greater number of negative
      life events interacted to predict increased bulimic symptoms, but not restrictive
      eating tendencies or symptoms of depression or anxiety. DISCUSSION: Low perceived
      social support in the face of negative events may exacerbate bulimic symptoms.
      Management of interpersonal problems and the enhancement of social skills may be
      important targets in the treatment of eating disorders.

PMID- 21184971
TI  - A laboratory-based study of mood and binge eating behavior in overweight
      children.
AB  - PURPOSE: Associations between negative mood and binge eating in the laboratory
      are well-established in adults, but such data are limited in youth. We
      investigated the relation between mood and binge eating in children using a
      laboratory feeding paradigm. METHOD: Overweight girls, aged 6-12 years, with (BE;
      n=23) and without (control, CON; n=23) reported objective and/or subjective binge
      eating underwent both sad and neutral mood inductions, followed by multi-item
      buffet meals. RESULTS: The Group * Mood Condition interaction for overall energy
      intake was non-significant. However, BE girls consumed more energy from fat in
      the sad condition as compared to the neutral condition. Baseline mood predicted
      BE girls' likelihood of reporting loss of control during the sad condition test
      meal. CONCLUSIONS: Results suggest that emotional eating episodes in children
      reporting aberrant eating may be characterized by the experience of loss of
      control, rather than the consumption of objectively large amounts of food.
      Interventions focused on affect regulation may minimize the adverse consequences
      of pediatric binge eating.

PMID- 21184973
TI  - Eating disorder pathology and menstrual cycle fluctuations in eating variables in
      oral contraceptive users and non-users.
AB  - Food intake and food cravings fluctuate across the menstrual cycle in women who
      are not using oral contraceptives (OCs), however less is known about cyclical
      variations in eating variables in women using OCs. Furthermore, few studies have
      examined the relationship between eating disorder pathology and menstrual cycle
      fluctuations in eating behaviors. In the present study, we examined self-report,
      retrospective ratings of food cravings intensity, hunger level, and amount eaten
      across the menstrual cycle in 67 non-OC users and across exogenous hormone
      regimens in 81 OC users. We also investigated the relationship between eating
      disorder pathology and cyclical fluctuations in eating variables. The results
      indicated that OC users and non-OC users report similar levels of food cravings
      and amount eaten across cycle phases, with food cravings and reported amount
      eaten elevated during the week prior to menses/hormone withdrawal bleeding and
      during the week of menses/hormone withdrawal bleeding. However, OC users reported
      elevated hunger during both the week prior to hormone withdrawal bleeding and
      during hormone withdrawal bleeding, whereas non-OC users reported an elevation in
      hunger level only during the week prior to menses. Fear of fatness and other
      eating disorder pathology variables were significantly associated with increases
      in food cravings, hunger level and reported amount eaten the week prior to menses
      in non-OC users, but not in OC users. These findings suggest that future studies
      should examine the potential role of menstrual cycle-related fluctuations in
      eating variables on the development of eating disorders.

PMID- 21184974
TI  - Biases in emotional processing are associated with vulnerability to eating
      disorders over time.
AB  - Biases in emotional processing are thought to play a role in the maintenance of
      eating disorders (EDs). In a previous study (Pringle et al., 2010), we were able
      to demonstrate that biases in the processing of negative self beliefs (a self
      schema processing task), facial expressions of emotion (a facial expression
      recognition task) and information relating to eating, shape and weight (an
      emotional Stroop) were all predictive of the level of subclinical ED symptoms
      (used here as a measure of risk) cross-sectionally in a vulnerable sample of
      dieters. The present study was a 12-month follow up of the participants from
      Pringle et al. (2010). Longitudinally, greater endorsement of ED relevant and
      depression relevant negative self beliefs in the self-schema processing task at
      time 1 was related to subclinical ED systems (level of risk) 12 months later at
      time 2. Compared to the cross-sectional study, there was no clear relationship
      between performance on the facial expression recognition task, emotional Stroop
      task and level of risk 12 months later. Although these findings are preliminary,
      one tentative interpretation may be that whilst biases in the processing of ED
      specific stimuli are predictive of level of risk at a given moment, over time
      less specific stimuli relating to beliefs about the self, including mood related
      variables, are more closely related to level of risk.

PMID- 21184976
TI  - Weight perception in female athletes: associations with disordered eating
      correlates and behavior.
AB  - Although weight perception is associated with disordered eating correlates and
      unhealthy eating behavior, it is unclear whether these associations exist in
      specific female populations at greater risk of disordered eating (i.e.,
      athletes). The aim of this study was to examine associations between weight
      perception and disordered eating correlates (perfectionism and social physique
      anxiety (SPA)) and eating behavior in female athletes. Measures of perfectionism
      (positive and negative), SPA, weight perception and disordered eating were
      completed by 136 female elite athletes. Athletes with overweight perceptions
      reported greater negative perfectionism, higher SPA and more disordered eating
      behavior than female athletes with normal-weight perceptions. Overweight
      perceptions are, therefore, an additional factor to consider in the relationship
      between perfectionism, physique anxiety and disordered eating in female athletes.

PMID- 21184975
TI  - Outcome expectations and realizations as predictors of weight regain among
      dieters.
AB  - This prospective study tested whether (a) baseline outcome expectations regarding
      the benefits of a weight-loss diet, (b) 6-month outcome realizations regarding
      perceived benefits actually experienced, and/or (c) the interaction between them
      predicted 6-12-month weight regain among overweight/obese women randomized to one
      of four popular weight-loss diets (N=311). Positive 6-month realizations
      regarding improvements in physical shape and appearance predicted less 6-12-month
      weight regain among Atkins diet participants only (n=70), controlling for
      baseline expectations, the expectations-realization interaction, and initial
      weight loss. Atkins participants displayed three distinct patterns of regain
      based on levels of 6-month realizations and initial weight loss. Experimental
      research should investigate whether improving realizations leads to reduced
      weight regain in response to this popular diet.

PMID- 21184977
TI  - Translation of the Quality of Life for Eating Disorders questionnaire into Hindi.
AB  - OBJECTIVE: The Quality of Life for Eating Disorders questionnaire was translated
      into Hindi (QOL ED-H) using the forward-backward translation procedure for use
      with Indian females. METHOD: A total of ninety-five females were recruited from
      two secondary schools and one tertiary college from Delhi, India. They were aged
      between 14 and 37 years, ranging from low to high socioeconomic status
      communities. A psychologist and teacher produced a preliminary Hindi version,
      which was back-translated by the psychologist and a journalist and any disparity
      was checked. The Hindi and English versions were administered one week apart to
      the same participants, the order being randomised. RESULTS: Repeated measures
      analysis revealed no significant differences in QOL ED scores (global and
      subscores) between the Hindi and English versions, when controlled for age.
      CONCLUSION: The QOL ED-H can be used to assess eating and exercise disordered
      thinking, feeling, behaviours, psychological feelings and daily living in Indian
      females of all SES groups.

PMID- 21184978
TI  - African and Caucasian body ideals in South Africa and the United States.
AB  - African women are often thought to be protected from developing eating disorder
      pathology because they experience less cultural pressure to be thin. Yet, to our
      knowledge, no previous study has quantified the African body ideals portrayed by
      the media. We determined the African and Caucasian body ideals portrayed by the
      media in the United States (US) and South Africa (RSA), by calculating the
      average body mass index of male and female fashion models in the respective
      countries. The African female body ideal was significantly heavier than the
      Caucasian body ideal in the US, but significantly thinner than the Caucasian body
      ideal in RSA. The African male body ideal was significantly thinner than the
      Caucasian body ideal in both countries. Findings indicate that the body ideals
      portrayed by the media parallel the previously reported eating disorder pathology
      for both sexes, and in both countries.

PMID- 21184979
TI  - Comparing live and remote models in eating conformity research.
AB  - Research demonstrates that people conform to how much other people eat. This
      conformity occurs in the presence of other people (live model) and when people
      view information about how much food prior participants ate (remote models). The
      assumption in the literature has been that remote models produce a similar effect
      to live models, but this has never been tested. To investigate this issue, we
      randomly paired participants with a live or remote model and compared their
      eating to those who ate alone. We found that participants exposed to both types
      of model differed significantly from those in the control group, but there was no
      significant difference between the two modeling procedures.

PMID- 21184980
TI  - Eating disorders in adolescents: correlations between symptoms and central
      control of eating behavior.
AB  - The aim of this study was to verify the relationship between eating disorders
      (binge eating and bulimia nervosa) and body image dissatisfaction with BMI,
      anorexigenic and orexigenic factors in adolescents. Thirty-two adolescents, (13
      obese [BMI=36.65+/-5.68] and 19 non-obese [BMI=22.18+/-3.11]), aged between 14
      and 19y, were recruited. Symptoms of eating disorders were measured by self
      report questionnaires (BSQ, BITE and BES). Hormones, cytokines and neuropeptides
      were determined by Elisa kits (Phoenix peptide). A positive correlation was found
      between: leptin and BES (r=.724), BSQ (r=.705) and BITE (r=.696); BMI and BES
      (r=.663), BSQ (r=.525) and BITE (r=.732); the same pattern was observed to
      insulin and TNF-alpha. A negative correlation was found in alpha-MSH and AgRP
      with BES, BSQ and BITE. Blood levels of hormones and neuropeptides could be the
      link between obesity and eating disorders in adolescents. However, it is not
      clear which is the cause and which is the consequence.

PMID- 21184981
TI  - Differences between grandiose and vulnerable narcissism and bulimic symptoms in
      young women.
AB  - Researchers have found some evidence of a link between narcissism and bulimia
      nervosa (BN). It is increasingly recognized, however, that there are two forms of
      narcissism: grandiose and vulnerable. Unfortunately, extant research on this
      relation has failed to distinguish between these forms. This is important as they
      differ in underlying traits, etiology, and outcomes. In the current study, we
      examined the relations between grandiose and vulnerable narcissism and BN and
      tested whether the relation between vulnerable narcissism and BN is confounded by
      trait levels of neuroticism. As hypothesized, only vulnerable narcissism was
      related with BN symptoms and much of this relation was explained by neuroticism.
      Future research should examine what vulnerable narcissism adds to the prediction
      of BN above and beyond neuroticism.

PMID- 21184982
TI  - Unwanted sexual experiences, depressive symptoms and disordered eating among
      college students.
AB  - Unwanted sexual experiences occurring only in young adulthood have rarely been
      explored. A sample of 122 college women completed a questionnaire survey
      assessing previous unwanted sexual experiences, sexual satisfaction, depressive
      symptoms and disordered eating. Seventeen percent reported unwanted sexual
      experiences. Results indicated that unwanted sexual experiences were associated
      with disordered eating and depressive symptoms, but that sexual satisfaction was
      not. Furthermore, the relationship between unwanted sexual experiences and
      disordered eating was mediated by depressive symptoms. These findings emphasize
      the high rates of unwanted sexual experiences in student populations, and suggest
      that victims of these experiences should be screened for depression.

PMID- 21184983
TI  - Avoidance of affect in the eating disorders.
AB  - The Distress Tolerance Scale (DTS) (Corstorphine, Mountford, Tomlinson, Waller, &
      Meyer, 2007) measures the tendency to use cognitive and behavioural strategies to
      manage the experience of positive and negative affect. This paper aimed to
      explore the factor structure of the DTS, particularly in relation to avoidance of
      affect. Participants were 227 female university students (non-clinical sample)
      and 257 clients seeking treatment for an eating disorder (clinical sample).
      Confirmatory factor analysis was used to test two previously proposed factor
      structures of the DTS in the non-clinical sample. Both of these models were found
      to be a poor fit to the data. Subsequently, nine items measuring avoidance of
      affect were analysed using exploratory factor analysis in the non-clinical
      sample. Three factors of avoidance of affect were identified (Behavioural
      Avoidance of Positive Affect, Behavioural Avoidance of Negative Affect, and
      Cognitive Avoidance of Affect). Confirmatory factor analysis supported this
      avoidance of affect model in the clinical sample. Significant correlations were
      observed between avoidance of affect subscales and eating psychopathology in both
      samples. Results suggest that the avoidance of positive emotion may be an
      important factor in eating disorders. It is recommended that future studies
      broaden their investigation of the role of emotion in eating disorders to include
      both negative and positive emotion.

PMID- 21184984
TI  - The relationship between body weight (body mass index) and attachment history in
      young women.
AB  - OBJECTIVE: This study investigated whether attachment history predicts unique
      variance in body mass index in young women. METHOD: A cross-sectional design was
      employed. One hundred and forty five women completed self report measures of
      attachment history and psychological symptoms. RESULTS: The findings indicated
      that negative parental discipline predicted significant variance in body mass
      index when common variance associated with demographic and psychological symptom
      measures was taken into account. CONCLUSIONS: It is concluded that attachment
      history may contribute to overweight and obesity and may be an important factor
      to consider in the prevention and treatment of overweight in women.

PMID- 21184987
TI  - Identifying patients at risk for premature discontinuation of thienopyridine
      after coronary stent implantation.
AB  - We sought to identify patients at risk for premature discontinuation of
      thienopyridines and to develop a risk score for thienopyridine adherence after
      coronary stent implantation. Patients were prospectively included from December
      2007 to March 2008. At 1-month follow-up, all patients were given the Morisky
      questionnaire and asked if they had stopped taking thienopyridines. Multivariate
      analysis identified predictors of thienopyridine discontinuation; points were
      assigned to each variable according to the odds ratios and the c-statistic of the
      score was calculated. Mean age of the 400 patients included was 61.0 +/- 10.4
      years; 66 patients (16.5%) stopped thienopyridines after 1 month. Reasons for
      discontinuation were cost (62%), lack of information (17%), and recommendation by
      another doctor to stop treatment (15%). Factors associated with discontinuation
      included unmarried status (odds ratio 2.48, p = 0.046), lack of private health
      insurance (odds ratio 4.68, p = 0.041), acute coronary syndrome (odds ratio 2.31,
      p = 0.004), nondiabetics (odds ratio 2.20, p = 0.041), and patients who earned <2
      times (odds ratio 8.23, p <0.001) and 2 to 3 times (odds ratio 4.46, p = 0.021)
      the minimum wage. Total risk score was 0 to 14 points and was strongly associated
      with thienopyridine discontinuation. For total scores of 0 to 4, 5 to 8, 9 to 12,
      and >=13, 0%, 7%, 20%, and 37% of patients, respectively, stopped thienopyridines
      (c-statistic 0.76, p <0.0001). Risk score was also significantly associated with
      complete adherence as assessed by the Morisky questionnaire (c-statistic 0.74, p
      <0.001). In conclusion, we have identified patients at risk for premature
      discontinuation of thienopyridines using variables obtained before stent
      implantation and developed a risk score that accurately predicts premature
      thienopyridine discontinuation.

PMID- 21184988
TI  - Trials on the effect of cardiac resynchronization on arterial blood pressure in
      patients with heart failure.
AB  - Cardiac resynchronization therapy (CRT) increases cardiac performance in patients
      with heart failure, but its effect on arterial pressure is not well established.
      To determine the effect of CRT on systolic blood pressure (SBP), diastolic blood
      pressure (DBP), and pulse pressure (PP) a systematic review using standard
      nomenclatures for CRT was done in Scopus (MEDLINE and Embase), Cochrane
      Controlled Trials Register, National Institutes of Health
      http://www.ClinicalTrials.gov database, and bibliography of select meta-analyses
      for studies evaluating CRT in patients with dilated cardiomyopathy. Two
      independent investigators extracted the articles based on predefined criteria.
      The primary outcome was difference in arterial pressure parameters from baseline
      to after CRT in nonrandomized cohort trials. This was then validated by comparing
      the change in arterial pressure between CRT and medical therapy groups in
      randomized controlled trials. A random-effects model was used for analyses.
      Analyses of 15 nonrandomized studies showed that CRT resulted in an increase
      (from baseline) in SBP by 4.4 mm Hg (95% confidence interval [CI] 0.8 to 8.0, p =
      0.02), no change in DBP (p = 0.21), and an increase in PP by 2.8 mm Hg (95% CI
      1.0 to 4.6, p = 0.003). Results from the 3 randomized controlled trials were
      concordant with an increase in SBP by 3.9 mm Hg (95% CI 1.1 to 6.8, p = 0.007),
      no effect on DBP (p = 0.40), and an increase in PP by 4.3 mm Hg (95% CI 4.1 to
      4.5, p <0.001) compared to medical therapy. In conclusion, CRT is associated with
      a modest increase in SBP and PP in patients with heart failure.

PMID- 21184989
TI  - Usefulness of cooling and coronary catheterization to improve survival in out-of
      hospital cardiac arrest.
AB  - Survival rates after out-of-hospital cardiac arrest (OHCA) continue to be poor.
      Recent evidence suggests that a more aggressive approach to postresuscitation
      care, in particular combining therapeutic hypothermia with early coronary
      intervention, can improve prognosis. We performed a single-center review of 125
      patients who were resuscitated from OHCA in 2 distinct treatment periods, from
      2002 to 2003 (control group) and from 2007 to 2009 (contemporary group). Patients
      in the contemporary group had a higher prevalence of cardiovascular risk factors
      but similar cardiac arrest duration and prehospital treatment (adrenaline
      administration and direct cardioversion). Rates of cardiogenic shock (48% vs 41%,
      p = 0.2) and decreased conscious state on arrival (77% vs 86%, p = 0.2) were
      similar in the 2 cohorts, as was the incidence of ST-elevation myocardial
      infarction (33% vs 43%, p = 0.1). The contemporary cohort was more likely to
      receive therapeutic hypothermia (75% vs 0%, p <0.01), coronary angiography (77%
      vs 45%, p <0.01), and percutaneous coronary intervention (38% vs 23%, p = 0.03).
      This contemporary therapeutic strategy was associated with better survival to
      discharge (64% vs 39%, p <0.01) and improved neurologic recovery (57% vs 29%, p
      <0.01) and was the only independent predictor of survival (odds ratio 5.5, 95%
      confidence interval 1.2 to 26.2, p = 0.03). Longer resuscitation time, presence
      of cardiogenic shock, and decreased conscious state were independent predictors
      of poor outcomes. In conclusion, modern management of OHCA, including therapeutic
      hypothermia and early coronary angiography is associated with significant
      improvement in survival to hospital discharge and neurologic recovery.

PMID- 21184990
TI  - Clinical and prognostic relevance of echocardiographic evaluation of right
      ventricular geometry in patients with idiopathic pulmonary arterial hypertension.
AB  - The aim of the present study was to assess the clinical and prognostic
      significance of right ventricular (RV) dilation and RV hypertrophy at
      echocardiography in patients with idiopathic pulmonary arterial hypertension.
      Echocardiography and right heart catheterization were performed in 72 consecutive
      patients with idiopathic pulmonary arterial hypertension admitted to our
      institution. The median follow-up period was 38 months. The patients were grouped
      according to the median value of RV wall thickness (6.6 mm) and the median value
      of the RV diameter (36.5 mm). On multivariate analysis, the mean pulmonary artery
      pressure (p = 0.018) was the only independent predictor of RV wall thickness, and
      age (p = 0.011) and moderate to severe tricuspid regurgitation (p = 0.027) were
      the independent predictors of RV diameter. During follow-up, 22 patients died.
      The death rate was greater in the patients with a RV diameter >36.5 mm than in
      patients with a RV diameter <=36.5 mm: 15.9 (95% confidence interval 9.4 to 26.8)
      vs 6.6 (95% confidence interval 3.3 to 13.2) events per 100-person years (p =
      0.0442). In contrast, the death rate was similar in patients with RV wall
      thickness above or below the median value. However, among the patients with a RV
      wall thickness >6.6 mm, a RV diameter >36 mm was not associated with a poorer
      prognosis (p = 0.6837). In conclusion, in patients with idiopathic pulmonary
      arterial hypertension, a larger RV diameter is a marker of a poor prognosis but a
      greater RV wall thickness reduces the risk of death associated with a dilated
      right ventricle.

PMID- 21184991
TI  - Long-term follow-up of patients with first-time chest pain having 64-slice
      computed tomography.
AB  - A paucity of data on outcome of coronary multislice computed tomography (CT) is
      available. The aim of this study was to assess the long-term follow-up of 64
      slice CT in a homogenous patient group. In total 222 patients (136 men, 61%, 59
      +/- 11 years of age) with chest pain at intermediate risk of coronary artery
      disease (CAD) and no previous CAD underwent 64-slice CT. Coronary lesions were
      considered significant or not based on a threshold of 50% luminal narrowing.
      Plaques were classified as calcified, noncalcified, and mixed based on type. End
      point during follow-up was major adverse cardiac events (nonfatal myocardial
      infarction, unstable angina requiring hospitalization, myocardial
      revascularization). Coronary plaques were detected in 162 patients (73%).
      Coronary artery stenosis was significant in 62 patients. Normal arteries were
      found in 59 patients (27%). During a mean follow-up of 5 +/- 0.5 years, 30
      cardiac events occurred. Annualized event rates were 0% in patients with normal
      coronary arteries, 1.2% in patients with nonsignificant stenosis, and 4.2% in
      patients with significant stenosis (p <0.01). Predictors of cardiac events were
      presence of significant stenosis, proximal stenosis, and multivessel disease.
      Noncalcified and mixed plaques had the worse prognosis (p <0.05). In conclusion,
      64-CT provides long-term incremental value in patients at intermediate risk of
      CAD.

PMID- 21184992
TI  - An early and simple predictor of severe left main and/or three-vessel disease in
      patients with non-ST-segment elevation acute coronary syndrome.
AB  - Clopidogrel should be initiated as soon as possible in patients with non-ST
      segment elevation acute coronary syndrome (NSTE-ACS) except those who urgently
      require coronary artery bypass grafting (CABG). The present study assessed the
      ability to predict severe left main coronary artery and/or 3-vessel disease
      (LM/3VD) that would most likely require urgent CABG based on only clinical
      factors on admission in 572 patients with NSTE-ACS undergoing coronary
      angiography. Severe LM/3VD was defined as >=75% stenosis of LM and/or 3VD with
      >=90% stenosis in >=2 proximal lesions of the left anterior descending coronary
      artery and other major epicardial arteries. Patients were divided into the 3
      groups according to angiographic findings: no LM/3VD (n = 460), LM/3VD but not
      severe LM/3VD (n = 57), and severe LM/3VD (n = 55). Severe LM/3VD was associated
      with a higher rate of urgent CABG compared to no LM/3VD and LM/3VD but not severe
      LM/3VD (46%, 2%, and 2%, p <0.001). On multivariate analysis, degree of ST
      segment elevation in lead aVR was the strongest predictor of severe LM/3VD (odds
      ratio 29.1, p <0.001), followed by positive troponin T level (odds ratio 1.27, p
      = 0.044). ST-segment elevation >=1.0 mm in lead aVR best identified severe LM/3VD
      with 80% sensitivity, 93% specificity, 56% positive predictive value, and 98%
      negative predictive value. In conclusion, ST-segment elevation >=1.0 mm in lead
      aVR on admission electrocardiogram is highly suggestive of severe LM/3VD in
      patients with NSTE-ACS. Selected patients with this finding might benefit from
      promptly undergoing angiography, withholding clopidogrel to allow early CABG.

PMID- 21184993
TI  - Meta-analysis of B-type natriuretic peptide's ability to identify stress induced
      myocardial ischemia.
AB  - Studies in victims of sudden cardiac death and those surviving a cardiac arrest
      have confirmed that extent of coronary artery disease is similar in those with
      and without angina, suggesting that it is the presence of myocardial ischemia
      rather than associated symptoms that determine the prognosis. Experimental models
      show that hypoxic myocardial tissue results in production of extra B-type
      natriuretic peptide (BNP), suggesting that BNP could potentially serve as a
      biomarker of myocardial ischemia. We performed a meta-analysis of the studies
      that link BNP to inducible myocardial ischemia as indicated by noninvasive stress
      tests. Values of true positive, false positive, true negative, and false negative
      were calculated from the reported sensitivity, specificity, disease prevalence,
      and total number of patients studied. Sixteen studies reporting data on 2,784
      patients across 14 study populations were included in the final analysis. Mean
      age of participants was 55 to 69 years and 55% to 90% were men. Pooled
      sensitivity and specificity of BNP for detection of stress-induced myocardial
      ischemia were 71% (95% confidence interval [CI] 68 to 74) and 52% (95% CI 52 to
      54), respectively. Pooled diagnostic odds ratio was 3.5 (95% CI 2.46 to 5.04) and
      summary receiver operating characteristic curve revealed an area under the curve
      of 0.71 +/- 0.02 (mean +/- SE). In conclusion, this meta-analysis suggests that
      an increased BNP level can identify inducible ischemia as detected by standard
      noninvasive stress tests. This raises the possibility of a whole new role for BNP
      in the diagnosis and management of myocardial ischemia.

PMID- 21184994
TI  - Specific characteristics of sudden death in a mediterranean Spanish population.
AB  - Most of the data reported on sudden cardiac death has been from studies of Anglo
      Saxon patients. We conducted a study to ascertain the relation between sudden
      death (SD) and some epidemiologic, clinical, and biochemical parameters and to
      assess the coronary histopathologic aspects of subjects in a Spanish population
      who had died suddenly. A total of 204 subjects (86% men), aged 12 to 80 years
      (mean 54 +/- 15), who had died from out-of-hospital natural SD were evaluated.
      Only 15% of subjects had been previously diagnosed with heart disease. Pathologic
      evidence of underlying cardiovascular disease was found in 90% of cases, with
      coronary heart disease (CHD) the most frequent (58%). The CHD was acute coronary
      thrombosis in 41% and a stable plaque with luminal narrowing of >=75% in 59%. An
      old myocardial infarction was found in 31% of the SD victims. Cardiac hypertrophy
      was found in 48%, with no relation between the presence of cardiac hypertrophy
      and CHD. Patients with stable plaques had a greater heart weight than did those
      with acute coronary thrombosis (p = 0.02). Male gender, older age, smoking, and
      low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio of
      >=3 were associated with CHD. A greater percentage of patients with an eroded
      and/or ruptured plaque than patients with a stable plaque were smokers. Only
      smoking and a low-density lipoprotein/high-density lipoprotein cholesterol ratio
      of >=3 were associated with an eroded and/or ruptured plaque. In conclusion,
      compared with the findings from studies of Anglo-Saxon patients, a lower
      incidence of CHD and acute coronary thrombosis and a greater incidence of cardiac
      hypertrophy were found in SD victims of a Mediterranean Spanish population.

PMID- 21184995
TI  - Relation of pulse pressure to blood pressure response to exercise in patients
      with hypertrophic cardiomyopathy.
AB  - Almost one third of patients with hypertrophic cardiomyopathy (HC) will have an
      abnormal blood pressure response (ABPR) to exercise, and this has been associated
      with a greater risk of sudden cardiac death. In the present study, we examined
      the association between the steady (mean arterial pressure) and pulsatile (pulse
      pressure) blood pressure components as they relate to ABPR in patients with HC (n
      = 70). All patients completed a standard Bruce protocol during symptom-limited
      stress testing with concurrent hemodynamic measurements. Pulse pressure (PP) was
      significantly greater in patients with HC with an ABPR (n = 19) than in the
      patients with HC without an ABPR to exercise (p <0.05). According to binary
      logistic regression analysis, PP at rest was a significant predictor of ABPR in
      patients with HC (p <0.05). Mean arterial pressure was not significantly
      different between the 2 groups, nor was it a predictor of an ABPR in the presence
      of HC. Those within the greatest tertile of PP at rest were 4.8 times more likely
      to have an ABPR than those within the lowest PP tertile (95% confidence interval
      1.24 to 18.2, p <0.05). In conclusion, elevations in PP at rest might identify
      patients with HC at a greater risk of having an ABPR during exercise.

PMID- 21184996
TI  - Comparison of the effectiveness and safety of low-molecular weight heparin versus
      unfractionated heparin anticoagulation after heart valve surgery.
AB  - Although unfractionated heparin (UFH) is used routinely after heart valve surgery
      at many institutions, cardiovascular surgery patients have a particularly high
      risk for developing heparin-induced thrombocytopenia (HIT). The aim of this study
      was to compare the efficacy and safety of low-molecular-weight heparin (LMWH) or
      UFH after heart valve surgery by conducting a retrospective evaluation of
      consecutive cardiovascular surgery patients in whom the LMWH dalteparin (n = 100)
      was used as the postoperative anticoagulant. This group was compared to an
      earlier group of patients who received UFH (n = 103). The main outcomes included
      the efficacy of the anticoagulant regimens (determined by the incidence of valve
      thrombosis, arterial thromboembolic events, and venous thromboembolic events) and
      the safety (determined by major bleeding, HIT, thrombotic events in HIT-positive
      cases, and death). Overall, there were for fewer thrombotic events in the LMWH
      treated group (4% vs 11%, p = 0.11). There was a higher rate of bleeding events
      in the UFH-treated group (10% vs 3%, p = 0.08). Six patients in the UFH-treated
      group developed HIT, 4 of whom had thrombotic events (HIT with thrombosis). In
      the LMWH-treated group, 3 patients developed HIT, 1 of whom had HIT with
      thrombosis. In conclusion, in this study, an LMWH regimen after heart valve
      surgery was effective and safe, with fewer thrombotic, bleeding, HIT, and HIT
      with thrombosis events.

PMID- 21184997
TI  - Effect of insurance type on adverse cardiac events after percutaneous coronary
      intervention.
AB  - Previous studies have documented disparities in both access to invasive
      cardiovascular procedures and outcomes in patients with Medicaid, Medicare, or no
      insurance. Outcomes by insurance have yet not been examined in a percutaneous
      coronary intervention (PCI) population. Data from patients undergoing PCI from
      June 2000 to June 2009 were retrospectively analyzed. Insurance was categorized
      as private, Medicare, Medicaid, and uninsured, according to the primary insurance
      at discharge. The outcome variable of interest was major adverse cardiac events
      (a composite of death, Q-wave myocardial infarction, and target vessel
      revascularization) at 1 year. Multivariable Cox regression analysis was
      stratified according to age <65 and >=65 years. Of the 13,573 patients who had
      undergone PCI, 6,653 (49.0%) had private insurance, 6,150 (45.3%) had Medicare,
      486 (3.6%) had Medicaid, and 284 (2.1%) were uninsured. Of the patients <65 years
      old, Medicaid (hazard ratio [HR] 1.59, 95% confidence interval [CI] 1.04 to
      2.43), Medicare (HR 2.18, 95% CI 1.58 to 2.99), and no insurance (HR 2.41, 95% CI
      1.36 to 4.27) were associated with greater rates of adjusted major adverse
      cardiac events at 1 year compared with private insurance. Of the patients >=65
      years old, only Medicaid (HR 3.07, 95% CI 1.09 to 8.61) was associated with a
      greater rate of adjusted major adverse cardiac events at 1 year. In conclusion,
      patients with government-sponsored insurance and no insurance have worse
      cardiovascular outcomes than patients with private insurance after PCI at 1 year.
      This implies that the provision of health insurance alone might not have a
      dramatic effect on cardiovascular outcomes after PCI.

PMID- 21184998
TI  - Global variability in angina pectoris and its association with body mass index
      and poverty.
AB  - In the absence of a previous global comparison, we examined the variability in
      the prevalence of angina across 52 countries and its association with body weight
      and the poverty index using data from the World Health Organization-World Health
      Survey. The participants with angina were defined as those who had positive
      results using a Rose angina questionnaire and/or self-report of a physician
      diagnosis of angina. The body mass index (BMI) was determined as the weight in
      kilograms divided by the square of the height in meters. The poverty index (a
      standard score of socioeconomic status for a given country) was extracted from
      the United Nations' statistics. The associations of angina with the BMI and
      poverty index were analyzed cross-sectionally using univariate and multivariate
      analyses. The results showed that the total participants (n = 210,787) had an
      average age of 40.64 years. The prevalence of angina ranged from 2.44% in Tunisia
      to 23.89% in Chad. Those participants with a BMI of <18.5 kg/m(2) (underweight),
      25 to 29 kg/m(2) (overweight), or BMI >= 30 kg/m(2) (obese) had a significantly
      greater risk of having angina compared to those with a normal BMI (>= 18.5 but
      <25 k/m(2)). The odds ratios of overweight and obese for angina remained
      significant in the multilevel models, in which the influence of the country-level
      poverty status was considered. A tendency was seen for underweight status and a
      poverty index >14.65% to be associated with the risk of having angina, although
      these associations were not statistically significant in the multilevel models.
      In conclusion, significant variations were found in the anginal rates across 52
      countries worldwide. An increased BMI was significantly associated with the odds
      of having angina.

PMID- 21184999
TI  - Relation of bundle branch block to long-term (four-year) mortality in
      hospitalized patients with systolic heart failure.
AB  - There is controversy regarding type of bundle branch block (BBB) that is
      associated with increased mortality risk in patients with heart failure (HF). The
      present study was designed to explore the association between BBB pattern and
      long-term mortality in hospitalized patients with systolic HF. Risk of 4-year all
      cause mortality was assessed in 1,888 hospitalized patients with systolic HF
      (left ventricular ejection function <50%) without a pacemaker in a prospective
      national survey. Cox proportional hazards regression modeling was used to compare
      mortality risk in patients with right BBB (RBBB; 10%), left BBB (LBBB; 14%), and
      no BBB (76%) on admission electrocardiogram. At 4 years of follow up, mortality
      rates were highest in patients with RBBB (69%), intermediate in those with LBBB
      (63%), and lowest in those without BBB (50%, p <0.001). Multivariate analysis
      demonstrated a significant 36% increased mortality risk in patients with RBBB
      versus no BBB (p = 0.002) but no significant difference in mortality risk for
      patients with LBBB versus no BBB (hazard ratio 1.04, p = 0.66). RBBB versus LBBB
      was associated with a 29% (p = 0.035) increased risk for 4-year mortality in the
      total population and with a 58% (p = 0.015) increased risk in patients with
      ejection fraction <30%. In conclusion, RBBB but not LBBB on admission
      electrocardiogram is associated with a significant increased long-term mortality
      risk in hospitalized patients with systolic HF. Deleterious effects of RBBB
      compared to LBBB appear to be more pronounced in patients with more advanced left
      ventricular dysfunction.

PMID- 21185000
TI  - Usefulness of repeated N-terminal pro-B-type natriuretic peptide measurements as
      incremental predictor for long-term cardiovascular outcome after vascular
      surgery.
AB  - Plasma N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels improve
      preoperative cardiac risk stratification in vascular surgery patients. However,
      single preoperative measurements of NT-pro-BNP cannot take into account the
      hemodynamic stress caused by anesthesia and surgery. Therefore, the aim of the
      present study was to assess the incremental predictive value of changes in NT-pro
      BNP during the perioperative period for long-term cardiac mortality. Detailed
      cardiac histories, rest left ventricular echocardiography, and NT-pro-BNP levels
      were obtained in 144 patients before vascular surgery and before discharge. The
      study end point was the occurrence of cardiovascular death during a median follow
      up period of 13 months (interquartile range 5 to 20). Preoperatively, the median
      NT-pro-BNP level in the study population was 314 pg/ml (interquartile range 136
      to 1,351), which increased to a median level of 1,505 pg/ml (interquartile range
      404 to 6,453) before discharge. During the follow-up period, 29 patients (20%)
      died, 27 (93%) from cardiovascular causes. The median difference in NT-pro-BNP in
      the survivors was 665 pg/ml, compared to 5,336 pg/ml in the patients who died (p
      = 0.01). Multivariate Cox regression analyses, adjusted for cardiac history and
      cardiovascular risk factors (age, angina pectoris, myocardial infarction, stroke,
      diabetes mellitus, renal dysfunction, body mass index, type of surgery and the
      left ventricular ejection fraction), demonstrated that the difference in NT-pro
      BNP level between pre- and postoperative measurement was the strongest
      independent predictor of cardiac outcome (hazard ratio 3.06, 95% confidence
      interval 1.36 to 6.91). In conclusion, the change in NT-pro-BNP, indicated by
      repeated measurements before surgery and before discharge is the strongest
      predictor of cardiac outcomes in patients who undergo vascular surgery.

PMID- 21185001
TI  - Clinical challenges of genotype positive (+)-phenotype negative (-) family
      members in hypertrophic cardiomyopathy.

PMID- 21185002
TI  - Percutaneous coronary intervention for non ST-elevation acute coronary syndromes:
      which, when and how?
AB  - The presentation of patients with suspected non ST-elevation acute coronary
      syndromes is quite diverse. Therefore, the diagnostic workup and choice of
      treatment may vary accordingly. Major issues regarding the evaluation are the
      likelihood of the diagnosis and the risk for adverse events. These factors should
      guide the choice of diagnostic test. Patients with increased risk for ischemic
      events and patients with recurrent ischemia are most likely to benefit from
      revascularization. In addition, when percutaneous coronary intervention is
      considered, evidence suggests that sufficient time should be allowed for
      pharmacologic stabilization, reducing the possibility of periprocedurally
      inflicted myocardial infarction. However, postponement of intervention may lead
      to an increase of new spontaneous events, and high-risk patients should apply for
      revascularization soon after pharmacologic stabilization. The extent of
      revascularization performed by percutaneous coronary intervention depends
      predominantly on patient characteristics and anatomy but should be limited to
      flow-obstructive lesions. In conclusion, patients presenting with non-ST
      elevation acute coronary syndromes constitute a very diverse population;
      diagnostic workup, treatment, and the timing of a possible intervention should be
      tailored individually.

PMID- 21185003
TI  - Patient perception versus medical record entry of health-related conditions among
      patients with heart failure.
AB  - A shared understanding of medical conditions between patients and their health
      care providers may improve self-care and outcomes. In this study, the concordance
      between responses to a medical history self-report (MHSR) form and the
      corresponding provider documentation in electronic health records (EHRs) of 19
      select co-morbidities and habits in 230 patients with heart failure were
      evaluated. Overall concordance was assessed using the kappa statistic, and crude,
      positive, and negative agreement were determined for each condition. Concordance
      between MHSR and EHR varied widely for cardiovascular conditions (kappa = 0.37 to
      0.96), noncardiovascular conditions (kappa = 0.06 to 1.00), and habits (kappa =
      0.26 to 0.69). Less than 80% crude agreement was seen for history of arrhythmias
      (72%), dyslipidemia (74%), and hypertension (79%) among cardiovascular conditions
      and lung disease (70%) and peripheral arterial disease (78%) for
      noncardiovascular conditions. Perfect agreement was observed for only 1 of the 19
      conditions (human immunodeficiency virus status). Negative agreement >80% was
      more frequent than >80% positive agreement for a condition (15 of 19 [79%] vs 8
      of 19 [42%], respectively, p = 0.02). Only 20% of patients had concordant MSHRs
      and EHRs for all 7 cardiovascular conditions; in 40% of patients, concordance was
      observed for <=5 conditions. For noncardiovascular conditions, only 28% of MSHR
      EHR pairs agreed for all 9 conditions; 37% agreed for <=7 conditions.
      Cumulatively, 39% of the pairs matched for <=15 of 19 conditions. In conclusion,
      there is significant variation in the perceptions of patients with heart failure
      compared to providers' records of co-morbidities and habits. The root causes of
      this variation and its impact on outcomes need further study.

PMID- 21185005
TI  - Comparison of morbidity and mortality in diabetics versus nondiabetics having
      isolated coronary bypass versus coronary bypass plus valve operations versus
      isolated valve operations.
AB  - The impact of diabetes mellitus (DM) on the outcome of patients requiring cardiac
      surgery has been investigated in previous decades. However, the profile of
      cardiac surgical practice is changing in addition to changes in patients' risk
      profile, making the results inconclusive. In this study we sought to investigate
      the impact of DM on operative mortality and morbidity in patients undergoing
      cardiac surgery and adjust for patient and disease characteristics. In total
      10,709 patients (9,229 nondiabetics and 1,480 diabetics) were admitted to the
      study; 5,557 patients (1,012 diabetics) underwent an isolated coronary operation,
      1,775 patients (278 diabetics) underwent coronary plus valve operations, and
      3,337 patients (209 diabetics) underwent valve operations. To control for
      differences in patient and disease characteristics, a propensity score (for DM)
      was performed. DM increased crude morbidity and this difference was maintained
      after risk adjustment for propensity score; conversely, the crude operative
      mortality risk was higher in diabetics but not significantly after adjustment for
      propensity score. Thereafter, DM remained independently associated to operative
      mortality risk in the valve population only (odds ratio 2.53, 95% confidence
      interval 1.45 to 4.4, p = 0.001). In conclusion, DM has a significant impact on
      operative mortality of patients undergoing heart valve surgery. Although diabetic
      patients undergoing coronary operations are not at increased risk of operative
      mortality, morbidity is significantly affected in the overall population.

PMID- 21185004
TI  - Warfarin use and outcomes in patients with advanced chronic systolic heart
      failure without atrial fibrillation, prior thromboembolic events, or prosthetic
      valves.
AB  - Warfarin is often used in patients with systolic heart failure (HF) to prevent
      adverse outcomes. However, its long-term effect remains controversial. The
      objective of this study was to determine the association of warfarin use and
      outcomes in patients with advanced chronic systolic HF without atrial
      fibrillation (AF), previous thromboembolic events, or prosthetic valves. Of the
      2,708 BEST patients, 1,642 were free of AF without a history of thromboembolic
      events and without prosthetic valves at baseline. Of these, 471 patients (29%)
      were receiving warfarin. Propensity scores for warfarin use were estimated for
      each patient and were used to assemble a matched cohort of 354 pairs of patients
      with and without warfarin use who were balanced on 62 baseline characteristics.
      Kaplan-Meier and Cox regression analyses were used to estimate the association
      between warfarin use and outcomes during 4.5 years of follow-up. Matched
      participants had a mean age +/- SD of 57 +/- 13 years with 24% women and 24%
      African-Americans. All-cause mortality occurred in 30% of matched patients in the
      2 groups receiving and not receiving warfarin (hazard ratio 0.86, 95% confidence
      interval 0.62 to 1.19, p = 0.361). Warfarin use was not associated with
      cardiovascular mortality (hazard ratio 0.97, 95% confidence interval 0.68 to
      1.38, p = 0.855), or HF hospitalization (hazard ratio 1.09, 95% confidence
      interval 0.82 to 1.44, p = 0.568). In conclusion, in patients with chronic
      advanced systolic HF without AF or other recommended indications for
      anticoagulation, prevalence of warfarin use was high. However, despite a
      therapeutic international normalized ratio in those receiving warfarin, its use
      had no significant intrinsic association with mortality and hospitalization.

PMID- 21185007
TI  - Safety of lower activated clotting times during atrial fibrillation ablation
      using open irrigated tip catheters and a single transseptal puncture.
AB  - Guidelines largely based on closed-tip catheters recommend activated clotting
      times (ACTs) >300 to 350 seconds during atrial fibrillation (AF) ablation to
      prevent thrombus and char formation. Open irrigated tip catheters (OITC) may
      decrease complications and permit lower ACTs. This study evaluated factors
      contributing to vascular and hemorrhagic complications during AF ablation with
      emphasis on catheter type, anticoagulation level, procedural and clinical
      variables, and gender. In 1,122 AF ablations we examined catheter used, ACT
      level, gender, and complications. Target ACTs initially were >300 seconds and
      were decreased to 225 seconds for the OITC. Average ACT ranges were created:
      <250, 250 to 299, 300 to 350, and >350 seconds. Average ACT was <250 seconds in
      557 ablations (complication rate 1.62%). Cochran-Armitage analysis showed that
      complications increased linearly as ACT increased and peaked at 5.55% for
      ablations with ACTs >350 seconds (p = 0.038). Women were older (66 +/- 10 vs 60
      +/- 10 years, p <0.001) and had more paroxysmal AF (43% vs 28%, p = 0.007) and
      more hypertension (50% vs 40%, p = 0.013). Women received less heparin but were
      over-represented in higher ACT ranges (p <0.0001) consistent with a
      pharmacokinetic gender difference. There was no difference in vascular or
      hemorrhagic complications between men and women (2.3% vs 2.9%, p = 0.668).
      Multivariate logistic regression showed that only use of the OITC was associated
      with lower complication rates (p = 0.024). In conclusion, AF ablation with the
      OITC is safe with a target ACT of 225 seconds.

PMID- 21185006
TI  - Value of the surface electrocardiogram in detecting right ventricular dilatation
      in the presence of left bundle branch block.
AB  - Approximately 20% of patients with heart failure have left bundle branch block
      (LBBB) on surface electrocardiogram (ECG). In this group of patients, detection
      of right ventricular (RV) dilatation on standard ECG can be of clinical relevance
      because RV enlargement is an important prognostic marker. Consequently, the aim
      of this study was to evaluate diagnostic accuracy for several
      electrocardiographic criteria in determining significant RV dilatation in these
      patients. Standard 12-lead ECGs were obtained in 173 patients with heart failure
      and known LBBB. From the ECG, 3 criteria for RV dilatation were defined: presence
      of terminal positivity in lead aVR (late R wave in lead aVR), low voltage (<0.6
      mV) in all extremity leads, and an R/S ratio <1 in lead V(5). In addition, all
      patients underwent comprehensive echocardiographic evaluation including
      assessment of RV dimensions. Measurements were performed blinded to
      electrocardiographic results. Significant RV dilatation was defined as an RV base
      to-apex length >= 86 mm or an RV diastolic area >= 33 cm(2). Eighty-six patients
      (50%) had a late R wave in lead aVR, 36 patients (21%) had low voltage in
      extremity leads, and 67 patients (39%) had an R/S ratio <1 in lead V(5). An RV
      base-to-apex length >= 86 mm was present in 67 patients (39%), and 62 patients
      (36%) had an RV diastolic area >= 33 cm(2). Any combination of 2 to 3 positive
      criteria could predict an RV base-to-apex length >= 86 mm with a positive
      predictive value of 89% and a negative predictive value of 88%. Similarly, an RV
      diastolic area >= 33 cm(2) was predicted with a positive predictive value of 80%
      and a negative predictive value of 88%. In conclusion, combining 2 to 3 distinct
      electrocardiographic criteria allows for accurate detection of RV dilatation in
      patients with heart failure and LBBB.

PMID- 21185008
TI  - Frequency of cardiac events at four years among initially asymptomatic filipinos
      with the Brugada type 1 electrocardiographic pattern.
AB  - Brugada type 1 electrocardiographic (ECG) pattern occurs in 0.2% of Filipinos. A
      knowledge gap exists on the natural course of asymptomatic patients with Brugada
      type 1 ECG pattern. Most studies that reported cohort event rates were taken from
      hospitals or referral centers. This is the first cohort from an entire country
      where the subjects were selected randomly. The objective of this study was to
      describe the frequency of cardiac events at 4 and 6 years of 7 patients with
      Brugada type 1 ECG pattern of 3,907 patients previously screened from the general
      population of the Philippines during the National Nutrition and Health Survey.
      Personal interviews at year 4 using a structured questionnaire were conducted by
      1 of the investigators. Occurrences of major (syncope, seizure, unexplained
      accidents, sudden death) and minor events in subjects and their first- and second
      degree relatives were elicited. Six-year follow-up by text messaging was
      conducted to ascertain vital status and occurrence of cardiac events. All 7
      patients with Brugada type 1 ECG pattern were men. Three of the 7 initially
      asymptomatic subjects (43%, 95 confidence interval 6 to 80) developed a major
      cardiac event by the fourth year. Those with events were younger than those
      without events. All 7 were alive by the sixth year. No additional events were
      noted between the fourth and sixth years. In conclusion, cardiac events are
      considerable in initially asymptomatic Filipinos with Brugada type 1 ECG pattern.

PMID- 21185010
TI  - Inhibitory properties of Coffea canephora extract against oral bacteria and its
      effect on demineralisation of deciduous teeth.
AB  - OBJECTIVES: The antibacterial activity of Coffea canephora extract was evaluated
      in vitro against Streptococcus mutans and Streptococcus sobrinus. The viability
      of planktonic cells was analysed by susceptibility tests (MIC and MBC) and time
      kill assays. The effect of the extract on dental demineralisation was also
      investigated. METHODS: Primary 1st molar fragments (n=24) were inoculated with a
      saliva pool and sustained in a multiple plaque growth system for 10 days to form
      biofilm. The biofilm was treated with light roasted C. canephora extract at 20%,
      Milli-Q water (negative control) and chlorhexidine (positive control) once a day,
      during a week. Blank controls comprised fragments without treatment. Biofilm pH
      was monitored in the last day of treatment. Changes in tooth mineralisation were
      assessed by cross-sectional microhardness (CSMH) test. RESULTS: MIC and MBC for
      S. mutans were 7+/-2 mg/mL and 160+/-0 mg/mL, respectively, showing no activity
      for S. sobrinus. The extract produced a 4-log reduction in the number of colonies
      of S. mutans after 3-h treatment (p<0.05) with undiluted extract (20%) and MBC
      concentration (16%). There was no difference among negative/blank controls and
      coffee plaque pH. Differences between CSMH values of dental fragments subjected
      to the coffee extract and to chlorhexidine were not significant. At depths up to
      30 MUm from the enamel surface, coffee extract and chlorhexidine promoted higher
      CSMH values when compared to blank/negative controls (p<0.05). CONCLUSION: Our
      data suggest that light roasted C. canephora extract is beneficial as an
      anticariogenic substance.

PMID- 21185009
TI  - Functional null mutations of MSRB3 encoding methionine sulfoxide reductase are
      associated with human deafness DFNB74.
AB  - The DFNB74 locus for autosomal-recessive, nonsyndromic deafness segregating in
      three families was previously mapped to a 5.36 Mb interval on chromosome 12q14.2
      q15. Subsequently, we ascertained five additional consanguineous families in
      which deafness segregated with markers at this locus and refined the critical
      interval to 2.31 Mb. We then sequenced the protein-coding exons of 18 genes in
      this interval. The affected individuals of six apparently unrelated families were
      homozygous for the same transversion (c.265T>G) in MSRB3, which encodes a zinc
      containing methionine sulfoxide reductase B3. c.265T>G results in a substitution
      of glycine for cysteine (p.Cys89Gly), and this substitution cosegregates with
      deafness in the six DFNB74 families. This cysteine residue of MSRB3 is conserved
      in orthologs from yeast to humans and is involved in binding structural zinc. In
      vitro, p.Cys89Gly abolished zinc binding and MSRB3 enzymatic activity, indicating
      that p.Cys89Gly is a loss-of-function allele. The affected individuals in two
      other families were homozygous for a transition mutation (c.55T>C), which results
      in a nonsense mutation (p.Arg19X) in alternatively spliced exon 3, encoding a
      mitochondrial localization signal. This finding suggests that DFNB74 deafness is
      due to a mitochondrial dysfunction. In a cohort of 1,040 individuals (aged 53-67
      years) of European ancestry, we found no association between 17 tagSNPs for MSRB3
      and age-related hearing loss. Mouse Msrb3 is expressed widely. In the inner ear,
      it is found in the sensory epithelium of the organ of Corti and vestibular end
      organs as well as in cells of the spiral ganglion. Taken together, MSRB3
      catalyzed reduction of methionine sulfoxides to methionine is essential for
      hearing.

PMID- 21185012
TI  - Microwave-assisted efficient synthesis of aryl ketone beta-C-glycosides from
      unprotected aldoses.
AB  - Condensation between unprotected aldoses and dibenzoylmethane catalyzed by
      NaHCO(3) in the cosolvents EtOH and H(2)O (4:1) under microwave irradiation gave
      aryl ketone beta-C-glycosides 6b-i in higher yields (from 50% with C-riboside 6g
      up to 99% with C-glucoside 6b) and better anomeric selectivities (beta
      configuration >95%) in a shorter reaction time (90 min), compared with previous
      conventional methodologies. This method provides an attractive alternative to the
      existing means for the preparation of high value ketone beta-C-glycosides.

PMID- 21185011
TI  - Gene expression and genetic variation data implicate PCLO in bipolar disorder.
AB  - BACKGROUND: Genetic variation may contribute to differential gene expression in
      the brain of individuals with psychiatric disorders. To test this hypothesis, we
      identified genes that were differentially expressed in individuals with bipolar
      disorder, along with nearby single nucleotide polymorphisms (SNPs) that were
      associated with expression of the same genes. We then tested these SNPs for
      association with bipolar disorder in large case-control samples. METHODS: We used
      the Stanley Genomics Database to extract gene expression and SNP microarray data
      from individuals with bipolar disorder (n = 40) and unaffected controls (n = 43).
      We identified 367 genes that were differentially expressed in the prefrontal
      cortex of cases vs. controls (fold change > 1.3 and FDR q-value < .05) and 45
      nearby SNPs that were associated with expression of those same genes (FDR q-value
      < .05). We tested these SNPs for association with bipolar disorder in a meta
      analysis of genome-wide association studies (GWAS) including 4,936 cases and
      6,654 healthy controls. RESULTS: We identified 45 SNPs that were associated with
      expression of differentially expressed genes, including HBS1L (15 SNPs), HLA-DPB1
      (15 SNPs), AMFR (8 SNPs), PCLO (2 SNPs) and WDR41 (2 SNPs). Of these, one SNP
      (rs13438494), in an intron of the piccolo (PCLO) gene, was significantly
      associated with bipolar disorder (FDR adjusted p < .05) in the meta-analysis of
      GWAS. CONCLUSIONS: These results support the previous findings implicating PCLO
      in mood disorders and demonstrate the utility of combining gene expression and
      genetic variation data to improve our understanding of the genetic contribution
      to bipolar disorder.

PMID- 21185013
TI  - New chiral imidazolium ionic liquids from isomannide.
AB  - New chiral bis and mono-imidazolium ionic liquids derived from isomannide were
      synthesized. The structural features of the chiral organic cations impart a
      special arrangement of the chiral cavity. The new chiral chloride salts of
      isomannide derivatives are pivotal compounds for the synthesis of different
      organic ionic liquids. After metathesis different anions were associated to the
      chiral cations providing a new class of chiral ionic liquids.

PMID- 21185014
TI  - ESIMS and NMR studies on the selective deprotection of acetylated glucosides by
      dibutyltin oxide.
AB  - The reaction process for the selective deprotection of acetylated glucosides by
      dibutyltin oxide in methanol is investigated by using methyl 2,3,4,6-tetra-O
      acetyl-alpha-d-glucopyranoside as a model substrate with ESIMS and NMR
      techniques. According to the results, it is inferred that at first, dimeric 1,3
      dimethoxytetrabutyldistannoxane is formed by the reaction of dibutyltin oxide
      with methanol, and then the tetraorganodistannoxane reacts with the acetylated
      glucoside to produce glucoside-organotin complex intermediates. Finally, the
      complex intermediates are hydrolyzed leading to the free-OH glucoside and
      organotin acetate derivatives. The reaction is affected by neighboring group
      participation and steric hindrance, which allow for high selectivities among
      different acetyl groups in acetylated glucosides.

PMID- 21185015
TI  - Relationships of sociotropy and autonomy with dimensions of the Temperament and
      Character Inventory in healthy subjects.
AB  - The relationships of sociotropy and autonomy, the 2 personality traits postulated
      as vulnerability factors for depression, with 7 dimensions of the Temperament and
      Character Inventory, a comprehensive measure of personality, were studied in 305
      healthy subjects. Sociotropy and autonomy were assessed by the sociotropy and
      autonomy subscales, respectively, of the original 60-item Sociotropy-Autonomy
      Scale. In multiple regression analysis, sociotropy was significantly correlated
      with higher harm avoidance, reward dependence (RD), and self-transcendence (ST),
      and lower self-directedness; and the correlation was strongest with higher RD
      (beta = 0.27) and second strongest with lower self-directedness (beta = -0.25).
      Meanwhile, autonomy was significantly correlated with higher persistence and ST,
      and lower RD; and the correlations were especially strong with higher ST (beta =
      0.37) and lower RD (beta = -0.28). These results support Beck's concepts of these
      personality traits, that is, the orientation toward interpersonal relationships
      of sociotropy, and that toward mastery and independence of autonomy.

PMID- 21185016
TI  - Suicidality in the "prodromal" phase of schizophrenia.
AB  - OBJECTIVES: Patients with schizophrenia are at high risk for suicide ideation,
      attempts, and completed suicide. However, suicidal behavior during the prodromal
      phase of schizophrenia and a possible association between prodromal suicidal
      behavior and suicidality after the onset of overt psychosis are not studied.
      METHODS: One hundred six consecutively admitted schizophrenia patients with
      recent onset were evaluated retrospectively for prodromal symptoms and
      suicidality during the prodromal phase and after the onset of frank psychosis. In
      addition, 106 matched control subjects from the general population were evaluated
      for suicidality during the same age period of the prodromal phase of the
      corresponding patient. RESULTS: Suicide ideation and attempt during the prodromal
      period were reported in 25.5% and 7.5% of the patients, which are 3.8- and 8-fold
      greater than in the controls, respectively. Patients with suicidal behavior
      experienced a greater number of prodromal symptoms than those without. Prodromal
      depressive mood, marked impairment in role functioning, and tobacco smoking
      exerted an independent effect on suicide ideation, whereas depressive mood was
      the symptom significantly more frequent in patients with suicide attempt. Suicide
      attempts were associated with an earlier onset of prodromal symptoms and frank
      psychosis. All patients with prodromal suicide attempts were cigarette smokers.
      Suicide ideation during the prodromal phase was strongly associated with lifetime
      suicidality after the onset of frank psychosis. CONCLUSIONS: Suicidal behavior is
      quite common during the prodromal period. The association of smoking, depressive
      mood, impaired functioning, and a large number of prodromal symptoms,
      particularly in patients with an early onset of symptomatology, carries a
      substantially increased risk for suicide ideation. Particular care is needed in
      patients with prodromal suicide ideation after the onset of frank psychosis
      because the risk to attempt suicide is high.

PMID- 21185017
TI  - Mental imagery in congenital prosopagnosia: a reply to Gruter et al.

PMID- 21185018
TI  - [Cardiovascular prevention: more evidence].

PMID- 21185020
TI  - Potenza et al. Primary subtalar arthrodesis for the treatment of comminuted intra
      articular calcaneal fractures [Injury 41;2010:702-6].

PMID- 21185019
TI  - Does salpingectomy affect the ipsilateral ovarian response to gonadotropin during
      in vitro fertilization-embryo transfer cycles?
AB  - In a study on the influence of salpingectomy on the same patient ipsilateral
      ovarian response, 15 patients who were admitted to our department with the
      diagnosis of uni- or bilateral hydrosalpinges and who were successfully treated
      by laparoscopic salpingectomy were evaluated. The observed significant decrease
      in the ipsilateral ovarian response after salgingectomy, as reflected by the
      quantity of developing follicles during controlled ovarian hyperstimulation for
      IVF, should be presented to patients during the decision-making process, before
      offering salpingectomy for the treatment of hydrosalpinx.

PMID- 21185021
TI  - The relationship of vitamin D deficiency to statin myopathy.
AB  - OBJECTIVE: Our goal was to examine the interaction between vitamin D and statins
      and the possible role of vitamin D deficiency in statin myopathy. BACKGROUND: The
      vitamin D receptor is present in skeletal muscle and vitamin D deficiency can
      cause myopathy. Statins (3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors)
      are generally well tolerated, but have been associated with a spectrum of
      skeletal muscle complaints, ranging from myalgia and asymptomatic mild elevations
      of creatine kinase (CK) to rhabdomyolysis. There has been recent interest in the
      possible interaction between statin myopathy and vitamin D deficiency. We
      performed a systematic medical literature review to examine this possible
      relationship. METHODS: We identified English language articles relating statins,
      vitamin D and statin myopathy via a PubMed search through July 2010. Articles
      pertinent to the topic were reviewed in detail. RESULTS/CONCLUSIONS: Our review
      suggests that some but not all statins increase 25(OH) D levels. Two cross
      sectional studies have associated vitamin D deficiency with statin-associated
      myalgias, and suggested that that increasing vitamin D levels can reverse the
      myalgia. Nevertheless, given the quality and paucity of studies examining this
      possibility, additional studies are needed to examine the potential role of
      vitamin D deficiency in statin myopathy. It is presently premature to recommend
      vitamin D supplementation as treatment for statin associated muscle complaints in
      the absence of low vitamin D levels although such supplementation could be tried
      in patients with deficient or reduced vitamin D levels.

PMID- 21185022
TI  - Increased skeletal muscle phosphocreatine recovery after sub-maximal exercise is
      associated with increased carotid intima-media thickness.
AB  - BACKGROUND: The association between skeletal muscle mitochondrial function and
      CVD risk in healthy subjects is unknown. METHODS: Forty subjects were evaluated
      for CVD risk with lipid profile, oral glucose tolerance test and measurement of
      carotid intima-media thickness (cIMT). Skeletal muscle mitochondrial function was
      determined by phosphocreatine recovery after sub-maximal exercise with
      (31)Phosphorous-MRS and represented as tauPCr. RESULTS: tauPCr was positively
      associated with age (r=+0.41; P=0.009) and cIMT (r=+0.50; P=0.001) on univariate
      analyses. In multivariate regression analysis controlling for age, the
      association between tauPCr and cIMT remained significant (beta=0.003; P=0.03).
      This association remained significant after controlling for traditional risk
      factors for CVD including age, gender, tobacco use, BMI, blood pressure,
      cholesterol and fasting glucose in a combined model (beta=0.003; P=0.04;
      R(2)=0.53; P=0.008 for overall model). CONCLUSIONS: These data suggest a novel
      association between skeletal muscle tauPCr and increased cIMT, independent of age
      or traditional CVD risk factors.

PMID- 21185023
TI  - Comparison of glenohumeral motion using different rotation sequences.
AB  - Glenohumeral motion presents challenges for its accurate description across all
      available ranges of motion using conventional Euler/Cardan angle sequences
      without singularity. A comparison of the description of glenohumeral motion was
      made using the ISB recommended YX'Y" sequence to the XZ'Y" sequence. A direct in
      vivo method was used for the analysis of dynamic concentric glenohumeral joint
      motion in the scapular plane. An electromagnetic tracking system collected data
      from ten healthy individuals while raising their arm. There were differences in
      the description of angular position data between the two different sequences. The
      YX'Y" sequence described the humerus to be in a more anteriorly rotated and
      externally rotated position compared to XZ'Y" sequence, especially, at lower
      elevation angles. The description of motion between increments using XZ'Y"
      sequence displacement decomposition was comparable to helical angles in magnitude
      and direction for the study of arm elevation in the scapular plane. The
      description of the direction or path of motion of the plane of elevation using
      YX'Y" angle decomposition would be contrary to that obtained using helical
      angles. We recommend that this alternate sequence (XZ'Y") should be considered
      for describing glenohumeral motion.

PMID- 21185024
TI  - Insights into chiral recognition mechanisms in supercritical fluid
      chromatography. II. Factors contributing to enantiomer separation on tris-(3,5
      dimethylphenylcarbamate) of amylose and cellulose stationary phases.
AB  - In this second part of our work on enantioselective supercritical fluid
      chromatography (SFC), we investigate the factors participating in the chiral
      recognition process on tris-(3,5-dimethylphenylcarbamate) of amylose and
      cellulose chiral stationary phases (CSPs). 135 racemates with diverse structures
      were analysed under identical SFC conditions on both stationary phases. The
      possibility of identifying the differential interactions of an enantiomer pair
      within the chromatographic system is assessed using a modified version of the
      solvation parameter model and factorial discriminant analysis. It is illustrated
      that one relationship of intermolecular interactions is insufficient to express
      the enantioseparation of different groups of racemates. An innovative approach is
      used in unravelling the interactions taking part in the enantiorecognition
      process. Different intermolecular interactions participating in the enantiomeric
      separation are demonstrated between the two stationary phases.

PMID- 21185025
TI  - Optimizing pressurized liquid extraction of microbial lipids using the response
      surface method.
AB  - Response surface methodology (RSM) was used for the determination of optimum
      extraction parameters to reach maximum lipid extraction yield with yeast. Total
      lipids were extracted from oleaginous yeast (Rhodotorula glutinis) using
      pressurized liquid extraction (PLE). The effects of extraction parameters on
      lipid extraction yield were studied by employing a second-order central composite
      design. The optimal condition was obtained as three cycles of 15 min at 100
      degrees C with a ratio of 144 g of hydromatrix per 100 g of dry cell weight.
      Different analysis methods were used to compare the optimized PLE method with two
      conventional methods (Soxhlet and modification of Bligh and Dyer methods) under
      efficiency, selectivity and reproducibility criteria thanks to gravimetric
      analysis, GC with flame ionization detector, High Performance Liquid
      Chromatography linked to Evaporative Light Scattering Detector (HPLC-ELSD) and
      thin-layer chromatographic analysis. For each sample, the lipid extraction yield
      with optimized PLE was higher than those obtained with referenced methods
      (Soxhlet and Bligh and Dyer methods with, respectively, a recovery of 78% and 85%
      compared to PLE method). Moreover, the use of PLE led to major advantages such as
      an analysis time reduction by a factor of 10 and solvent quantity reduction by
      70%, compared with traditional extraction methods.

PMID- 21185026
TI  - Development of a sensitive non-targeted method for characterizing the wine
      volatile profile using headspace solid-phase microextraction comprehensive two
      dimensional gas chromatography time-of-flight mass spectrometry.
AB  - Future understanding of differences in the composition and sensory attributes of
      wines require improved analytical methods which allow the monitoring of a large
      number of volatiles including those present at low concentrations. This study
      presents the optimization and application of a headspace solid-phase
      microextraction (HS-SPME) method for analysis of wine volatiles by comprehensive
      two-dimensional gas chromatography (GC*GC) time-of-flight mass spectrometry
      (TOFMS). This study demonstrates an important advancement in wine volatile
      analysis as the method allows for the simultaneous analysis of a significantly
      larger number of compounds found in the wine headspace compared to other current
      single dimensional GC-MS methodologies. The methodology allowed for the
      simultaneous analysis of over 350 different tentatively identified volatile and
      semi-volatile compounds found in the wine headspace. These included potent aroma
      compound classes such as monoterpenes, norisoprenoids, sesquiterpenes, and alkyl
      methoxypyrazines which have been documented to contribute to wine aroma. It is
      intended that wine aroma research and wine sensory research will utilize this non
      targeted method to assess compositional differences in the wine volatile profile.

PMID- 21185027
TI  - Determination of UV filters in packaging by focused ultrasonic solid-liquid
      extraction and liquid chromatography.
AB  - A focused ultrasonic solid-liquid extraction (FUSLE) and high performance liquid
      chromatography (HPLC) with a diode array detector (DAD) is proposed for the
      determination of ten fat-soluble UV filters in packaging. FUSLE technique is
      relatively new and has been used for the extraction of a few analytes; such as
      polycyclic aromatic hydrocarbons and other organic pollutants. In this work, it
      has been demonstrated that FUSLE is a useful, fast and simple extraction
      methodology for UV filters because the complete extraction was carried out with
      just 6ml of tetrahydrofuran and in only one cycle of 30s. The developed method
      has been validated and applied to the analysis of polyethylene-based multilayer
      packaging samples. The FUSLE-based method allows the sensitive detection of most
      of the UV-filters in polyethylene, with limits of detection between 0.4 and
      8.5ngmg(-1) (except for BDM). Intra and inter-day relative standard deviation
      values were below 5 and 14%, respectively, except for MBP. In addition, the
      proposed method was more efficient than tetrahydrofuran extraction under reflux
      for 2.5h for all the analytes except for EMT and BDM. Therefore, the developed
      method can be used to establish the absorption capability of different types of
      packaging and this information will be very useful in packaging selection.

PMID- 21185028
TI  - Electrochemical preparation of polyaniline-ionic liquid based solid phase
      microextraction fiber and its application in the determination of benzene
      derivatives.
AB  - A polyaniline-ionic liquid (i.e. 1-butyl-3-methylimidazolium tetrafluoroborate,
      [C(4)mim][BF(4)]) composite film coated platinum wire (PANI-IL/Pt) was prepared
      by electrochemical method for the first time. Scanning electron microscopy image
      showed that the PANI-IL composite film was even and porous. When the PANI-IL/Pt
      was used as a fiber for the headspace solid-phase microextraction (HS-SPME) of
      some benzene derivatives (i.e. 1,3-dimethylbenzene, 1,2-dimethylbenzene, 1,4
      dichlorobenzene, 1,2-dichlorobenzene, 1,3,5-trimethylbenzene and 1,2,4
      trimethylbenzene), followed by gas chromatographic analysis, it presented
      excellent performance, which was much better than that of PANI/Pt and commercial
      polydimethylsiloxane fiber. Hence the fiber was coupled with gas chromatography
      for the determination of these benzene derivatives. It was found that under the
      optimized conditions the linear ranges were 0.04-400 MUg L(-1) with correlation
      coefficients above 0.99, the detection limits were 9.3-48.1 ng L(-1) (S/N=3), the
      relative standard deviations (RSDs) were smaller than 5.1% for five successive
      measurements with single fiber, and the RSDs for fiber-to-fiber were 5.0-11.1%
      (n=3) for different benzene derivatives. The proposed method was successfully
      applied to the extraction and determination of benzene derivatives in waste water
      and tap water, and the recoveries were 87.1-108.1% for different analytes.
      Therefore, the PANI-IL/Pt is a promising SPME fiber.

PMID- 21185029
TI  - Development of a quantitative high-performance thin-layer chromatographic method
      for sucralose in sewage effluent, surface water, and drinking water.
AB  - Sucralose, a persistent chlorinated substance used as sweetener, can already be
      found in waste water, and various countries focused on the release of sucralose
      into the aquatic environment. A quantitative high-performance thin-layer
      chromatography (HPTLC) method, which is orthogonal to existing methods, was
      developed to analyze sucralose in water. After sample preparation, separation of
      up to 17 samples was performed in parallel on a HPTLC plate silica gel 60 F(254)
      with a mixture of isopropyl acetate, methanol and water (15:3:1, v/v/v) within 15
      min. Due to the weak native UV absorption of sucralose (<=200 nm), various post
      chromatographic derivatization reactions were compared to selectively detect
      sucralose in effluent and surface water matrices. Thereby p-aminobenzoic acid
      reagent was discovered as a new derivatization reagent for sucralose. Compared to
      the latter and to beta-naphthol, derivatization with aniline diphenylamine o
      phosphoric acid reagent was slightly preferred and densitometry was performed by
      absorbance measurement at 400 nm. The limit of quantification (LOQ) of sucralose
      in drinking and surface water was calculated to be 100 ng/L for a given recovery
      rate of 80% and the extraction of a 0.5 L water sample. The sucralose content
      determined in four water samples obtained during an interlaboratory trial in 2008
      was in good agreement to the mean laboratory values of that trial. According to
      the t-test, which compares the results with the target value, the means obtained
      by HPTLC were not significantly different from the respective means of six
      laboratories, analyzed by HPLC-MS/MS or HPLC-TOF-MS with the use of mostly
      isotopically labeled standards. The good accuracy and high sample throughput
      capacity proved HPTLC as a well suited method regarding quantification of
      sucralose in various aqueous matrices.

PMID- 21185030
TI  - A new method of analysis of peroxydisulfate using ion chromatography and its
      application to the simultaneous determination of peroxydisulfate and other common
      inorganic ions in a peroxydisulfate matrix.
AB  - A new method for the determination of peroxydisulfate using ion chromatography
      has been developed. Elution of peroxydisulfate was effected by isocratic elution
      using 200 mM NaOH at 40 degrees C. A modification of the method using gradient
      elution was able to simultaneously determine other common inorganic ions
      (nitrate, nitrite, sulfate and chloride) down to significantly low concentrations
      in a peroxydisulfate matrix. The relative standard deviations (RSD) were in the
      range of 0.5-5%, for peak areas and <0.2% for peak retention times. The
      recoveries were between 95% and 120% for a concentration range of about 0.5-42
      ppm. The limit of detection for peroxydisulfate ion was 0.2 ppm and for the other
      ions were <=2*10(-2) ppm. The calibration curves were linear with slope and
      intercepts close to 1 and 0, respectively.

PMID- 21185031
TI  - Headspace hollow fiber protected liquid-phase microextraction combined with gas
      chromatography-mass spectroscopy for speciation and determination of volatile
      organic compounds of selenium in environmental and biological samples.
AB  - A simple and novel speciation method for the determination of volatile organic
      compounds of selenium (dimethylselenide (DMSe) and dimethyldiselenide (DMDSe) has
      been developed using a headspace hollow fiber protected liquid-phase
      microextraction (HS-HF-LPME) combined with capillary gas chromatography-mass
      spectrometry (GC-MS). The organic solvent impregnated in the pores and filled
      inside the porous hollow fiber membrane was used as an extraction interface in
      the HS-HF-LPME of the compounds. The effect of different variables on the
      extraction efficiency was studied simultaneously using an experimental design.
      The variables of interest in the HS-HF-LPME were sample volume, extraction time,
      temperature of sample solution, ionic strength, stirring rate and dwelling time.
      A Plackett-Burman design was performed for screening in order to determine the
      significant variables affecting the extraction efficiency. Then, the significant
      factors were optimized by a Box-Behnken design (BBD) and the response surface
      equations were derived. Under optimum conditions, preconcentration factors up to
      1250 and 1170 were achieved for DMSe and DMDSe respectively. The detection limit
      and relative standard deviation (RSD) (n=5, c=50 MUg L(-1)) for DMSe were 65 ng
      L(-1) and 4.8%, respectively. They were also obtained for DMDSe as 57 ng L(-1)
      and 3.9%, respectively. The developed technique was found to be applicable to
      spiked environmental and biological samples.

PMID- 21185032
TI  - Direct synthesis of acid-base bifunctionalized hexagonal mesoporous silica and
      its catalytic activity in cascade reactions.
AB  - A series of efficient acid-base bifunctionalized hexagonal mesoporous silica
      (HMS) catalysts contained aminopropyl and propanesulfonic acid have been
      synthesized through a simple co-condensation by protection of amino group. The
      results of small-angle XRD, TEM, and N(2) adsorption-desorption measurements show
      that the resultant materials have mesoscopic structures. X-ray photoelectron
      spectroscopies, elemental analysis (EA), back titration, (29)Si NMR and (13)C NMR
      confirm that the organosiloxanes were condensed as a part of the silica
      framework. The resultant catalysts exhibit excellent acid-basic properties, which
      make them possess high activity for one-pot deacetalization-Knoevenagel and
      deacetalization-nitroaldol (Henry) reactions.

PMID- 21185033
TI  - Suicidal ideation in treatment-seeking Veterans of Operations Enduring Freedom
      and Iraqi Freedom: the role of coping strategies, resilience, and social support.
AB  - BACKGROUND: Recent epidemiologic studies have found an increased risk of suicide
      among Veterans of Operations Enduring Freedom and Iraqi Freedom (OEF-OIF) with
      psychiatric disorders. However, little is known about whether variables other
      than psychiatric conditions, such as coping strategies, resilience, and social
      support, may be related to suicidality in this population. METHODS: A total of
      167 OEF-OIF Veterans seeking behavioral or primary care services completed a
      survey containing measures of combat exposure, psychopathology, pain,
      psychological resilience, social support, and cognitive coping strategies.
      RESULTS: Thirty-six respondents (21.6%) reported contemplating suicide in the two
      weeks prior to completing the survey. Compared to suicide non-contemplators,
      suicide contemplators were older, and more likely to screen positive for
      depression and posttraumatic stress disorder (PTSD), and to report a deployment
      related pain condition or complaint. They also scored higher on measures of
      worry, self-punishment, and cognitive-behavioral avoidance strategies, and lower
      on measures of psychological resilience and postdeployment social support.
      Multivariate analysis revealed that a positive depression screen, and higher
      scores on measures of self-punishment and cognitive-social avoidance coping were
      positively associated with suicidal ideation, while higher scores on measures of
      psychological resilience (i.e., positive acceptance of change) were negatively
      related to suicidal ideation. Moderator analysis revealed that a positive screen
      for depression or PTSD significantly diminished the protective effect of
      postdeployment social support on suicidal ideation. CONCLUSIONS: 1 in 5 treatment
      seeking OEF-OIF Veterans may contemplate suicide. Interventions to reduce
      depressive symptoms, and maladaptive cognitive-behavioral coping strategies of
      self-punishment and cognitive social avoidance, and to bolster psychological
      resilience may help mitigate suicidality in this population.

PMID- 21185034
TI  - Macrobenthos habitat mapping in a tidal flat using remotely sensed data and a GIS
      based probabilistic model.
AB  - This paper proposes and tests a method of producing macrofauna habitat potential
      maps based on a weights-of-evidence model (a probabilistic approach) for the
      Hwangdo tidal flat, Korea. Samples of macrobenthos were collected during field
      work, and we considered five mollusca species for habitat mapping. A weights-of
      evidence model was used to calculate the relative weights of 10 control factors
      that affect the macrobenthos habitat. The control factors were compiled as a
      spatial database from remotely sensed data combined with GIS analysis. The
      relative weight of each factor was integrated as a species potential index (SPI),
      which produced habitat potential maps. The maps were compared with the surveyed
      habitat locations, revealing a strong correlation between the potential maps and
      species locations. The combination of a GIS-based weights-of-evidence model and
      remote sensing techniques is an effective method in determining areas of
      macrobenthos habitat potential in a tidal flat setting.

PMID- 21185035
TI  - Effects of reclamation on macrobenthic assemblages in the coastline of the
      Arabian Gulf: a microcosm experimental approach.
AB  - Coastal reclamation and modifications are extensively carried out in Bahrain,
      which may physically smother the coastal and subtidal habitats resulting in
      changes to abundance and distribution of macrobenthic assemblages. A microcosm
      laboratory experiment using three common macrobenthic invertebrates from a
      proposed reclaimed coastal area was preformed to examine their responses to mud
      burial using marine sediment collected from a designated borrow area. Significant
      difference in numbers of survived organisms between control and experimental
      treatments with a survival percentage of 41.8% for all of the selected species
      was observed. The polychaete Perinereis nuntia showed the highest percentage of
      survival (57.1%) followed by the bivalve Tellinavaltonis (42.3%) and the
      gastropod Cerithidea cingulata (24.0%). Quantifying species responses to sediment
      burial resulted from dredging and reclamation will aid in predicting the expected
      ecological impacts associated with coastal developments and subsequently
      minimizing these impacts and maintaining a sustainable use of coastal and marine
      ecosystems in the Arabian Gulf.

PMID- 21185036
TI  - Are sea otters being exposed to subsurface intertidal oil residues from the Exxon
      Valdez oil spill?
AB  - Twenty years after the Exxon Valdez oil spill, scattered patches of subsurface
      oil residues (SSOR) can still be found in intertidal sediments at a small number
      of shoreline locations in Prince William Sound, Alaska. Some scientists
      hypothesize that sea otters continue to be exposed to SSOR by direct contact when
      otters dig pits in search of clams. This hypothesis is examined through site
      specific examinations where SSOR and otter-dug pits co-occur. Surveys documented
      the exact sediment characteristics and locations on the shore at the only three
      subdivisions where both SSOR and otter pits were found after 2000. Shoreline
      characteristics and tidal heights where SSOR have persisted are not suitable
      habitat for sea otters to dig pits during foraging. There is clear separation
      between areas containing SSOR and otter foraging pits. The evidence allows us to
      reject the hypothesis that sea otters encounter and are being exposed by direct
      contact to SSOR.

PMID- 21185037
TI  - [New alliance between the Panamerican Health Organization and the EQUATOR Network
      to improve writing and publication of articles on health outcomes research].

PMID- 21185038
TI  - [Vitamin D deficiency and bone mineral density in Crohn's disease].
AB  - BACKGROUND AND OBJECTIVES: Inadequate serum levels of 25-hydroxyvitamin D
      (25OHD(3)) are deemed as a possible risk factor for osteoporosis in Crohn's
      disease (CD). Our aim is to determine the prevalence of inadequate serum levels
      of 25OHD(3) and its possible relationship with low bone mineral disease (BMD) in
      CD. PATIENTS AND METHODS: Sixty-four patients from the province of Granada
      (Spain) were enrolled. Serum levels of 25OHD3 and intact parathyroid hormone were
      measured. BMD was assessed by dual-energy x-ray absorptiometry at lumbar spine
      (LS) and femoral neck (FN). RESULTS: Almost 60% of patients showed inadequate
      serum levels of 25OHD(3), whereas only about 16% showed levels considered as
      adequate (>=30 ng/mL). Z-score at FN was <= -2 in 4.7% of patients and 20.3% at
      LS. Regarding T-score, 4.7 and 46.9% of patients met criteria for osteoporosis
      and osteopenia at FN, respectively, whereas 6.25 and 42.2% did it at LS,
      respectively. Patients with inadequate serum levels of 25OHD(3) had non
      significant lower BMD, both at the LS and the FN. CONCLUSIONS: Prevalence of
      inadequate serum levels of 25-(OH)D was high in our series. A no statistically
      significant tendency towards low BMD in patients with inadequate serum levels of
      25-(OH)D both at the FN and the LS was observed.

PMID- 21185039
TI  - [Risk factors for lower limbs vascular complications in diabetic patients].

PMID- 21185040
TI  - [What clinical guideline should we use for the management of osteoporosis?].

PMID- 21185041
TI  - Carnivorous pitcher plants: insights in an old topic.
AB  - Plant insect interactions are usually recognized as a scenario where herbivorous
      insects feed on a host plant. However, also the opposite situation is known,
      where plants feed on insects. Carnivorous pitcher plants of the genus Nepenthes
      as well as other pitcher plants obtain many nutrients from caught insect prey.
      Special features of the pitcher traps' surface are responsible for attraction and
      trapping insects. Once caught, the prey is digested in the fluid of the pitchers
      to release nutrients and make them available for the plant. Nutrients are taken
      up by special glands localized on the inner surface of the pitchers. These glands
      also secrete the hydrolyzing enzymes into the digestion fluid. Although this is
      known for more than 100 years, our knowledge of the pitcher fluid composition is
      still limited. Only in recent years some enzymes have been purified from the
      pitcher fluid and their corresponding genes could be identified. Among them, many
      pathogenesis-related proteins have been identified, most of which exhibiting
      hydrolytic activities. The role of these proteins as well as the role of
      secondary metabolites, which have been identified in the pitcher fluid, is
      discussed in general and in the context of further studies on carnivorous plants
      that might give answers to basic questions in plant biology.

PMID- 21185042
TI  - It's not just deprivation.

PMID- 21185043
TI  - Distribution of neuromedin S and its receptor NMU2R in pigs.
AB  - Neuromedin S (NMS) has been found to be involved in the regulation of the
      reproductive, endocrine, and immune systems in mammals. However, its function in
      pigs is currently not well understood. Thus, it is essential and important to
      characterize the central distribution of NMS mRNA and its receptor, neuromedin U
      receptor-2 (NMU2R), in pigs for clarifying its physiological functions. In this
      study, we found that NMS mRNA were densely distributed in the hypothalamus,
      hypophysis, hippocampus, and brain stem of pigs by in situ hybridization.
      Moreover, NMS and NMU2R mRNAs was also expressed in the alimentary organs,
      endocrine and lymphatic organs, and ovaries by semi-Q RT-PCR. All these results
      suggest that the NMS/NMU2R system plays an important role in modulating various
      physiological functions in pigs. This research provides useful information for
      predicting the physiological functions of the NMS/NMU2R system in pigs.

PMID- 21185044
TI  - [Ischemic strokes related to benign primitive cardiac tumours].
AB  - BACKGROUND: We report three cases of ischemic cardioembolic strokes related to
      benign primary cardiac tumours (two fibromas and one fibroelastoma). CASE
      REPORTS: This is a retrospective study over a five years period (from December
      2004 to December 2009) in a French community hospital. Data on hospital strokes
      were obtained from the informatics department. Three benign primary cardiac
      tumours were found as the cause of acute neurological manifestations: a 45-year
      old woman with a fibroelastoma revealed by a brain infarction, a 29-year-old man
      with a myxoma revealed by a transient ischemic attack, and a 46-year-old woman
      with a myxoma revealed by a brain infarction. Rankin scores performed at least 18
      months after cardiac tumour surgery were respectively of 0, 0 and 2. CONCLUSION:
      Our study confirms that this is a rare event even if those tumours seem to have a
      high embolic potential (myxomas). Anyway, long-term functional outcome seems to
      be good.

PMID- 21185045
TI  - Pharmacovigilance methods in public health programmes: the example of miltefosine
      and visceral leishmaniasis.
AB  - Pharmacovigilance is concerned with the assessment of benefit and harm. Disease
      burden, status of healthcare delivery through government centres and
      practitioners, existing pharmacovigilance programmes, relevant pre-marketing
      studies and the likely effectiveness and risks of drugs must be considered for
      planning pharmacovigilance activity. The risk of a drug may be known, unknown,
      potential or specific to the context of the programme. The potential benefits of
      a public health programme aimed at reducing or eliminating a specific condition
      will depend on the health burden due to that condition, which is a function of
      the seriousness of the condition and its frequency, as well as the likely
      efficacy of the programme in reaching its goals. The present article has outlined
      an approach to pharmacovigilance for such a donor-funded programme, using
      pharmacovigilance in leishmaniasis as an example.

PMID- 21185046
TI  - Effects of pesticide temephos on the gills of Aphanius dispar (Pisces:
      Cyprinodontidae).
AB  - The changes in the behavior of Aphanius dispar, a cyprinodont fish when exposed
      to different concentrations of temephos, an organophosphorus pesticide widely
      used to control mosquito larvae in aquatic habitats are noted. The histopathology
      of gills exposed to temephos is studied in detail using light microscopy (LM),
      transmission electron microscopy (TEM) and scanning electron microscopy (SEM).
      The gill lesions were seen in all exposed concentrations of 1, 5, 10 and 25 ppm
      and the magnitude of the damage increased with the increase in concentrations.
      The most adverse effects of temephos are the destruction of cartilage and the
      large-scale cell death. Other effects included the degradation of chloride cells
      (CCs), desquamation, epithelial lifting, hypertrophy and lamellar fusion. The
      histological changes of microridges did not follow a consistent pattern in
      exposed concentrations. However, lamellar curling and collapsing was common in
      all exposed fish.

PMID- 21185047
TI  - Competing roles of microRNA-122 recognition elements in hepatitis C virus RNA.
AB  - MicroRNA-122 positively modulates hepatitis C virus (HCV) through direct
      interactions with viral RNA. Three microRNA-122 recognition elements (MREs) have
      been previously identified: two in the 5'UTR and one in the 3'UTR. Herein, we
      report the relative affinity of microRNA-122 to these sites using viral RNA
      coated magnetic beads, with mutagenesis and probes to disrupt interactions of
      microRNA-122 at specific sites. We demonstrate cooperativity in binding between
      the closely spaced MREs within the 5'UTR in vitro. We also identified a well
      conserved fourth site in the coding region and showed that it is the highest
      affinity MRE site. Site-directed mutagenesis of the MREs in HCV subgenomic
      replicons expressed in Huh-7.5 cells demonstrated competing roles of the
      stimulatory MREs in the 5'UTR with the inhibitory role of an MRE in the open
      reading frame (ORF). These data have important implications in elucidating the
      mechanism of interaction between microRNA-122 and HCV RNA.

PMID- 21185048
TI  - Decoding arenavirus pathogenesis: essential roles for alpha-dystroglycan-virus
      interactions and the immune response.
AB  - Pathogenesis following a virus infection results from interactions between the
      virus and its host. The outcome is determined by tipping the balance between
      virulence of the virus or susceptibility/resistance of the host to favor one or
      the other. This review focuses on two important members of the Old World
      arenavirus family: Lassa fever virus (LFV), a robust human pathogen that causes a
      severe acute hemorrhagic disease; and lymphocytic choriomeningitis virus (LCMV),
      also a human pathogen but better known in the context of its rodent model.
      Research with this model has uncovered and illuminated many of our current
      concepts in immunobiology and viral pathogenesis. Presented here are recent
      advances that form the framework for a better understanding of how viruses induce
      and maintain persistent infection as well as for the pathogenesis associated with
      acute LFV infection. A major component for understanding the pathogenesis of
      these arenaviruses revolves around study of the interaction of virus with its
      receptor, alpha-dystroglycan (alpha-DG).

PMID- 21185049
TI  - Lineage replacement accompanying duplication and rapid fixation of an RNA element
      in the nsP3 gene in a species of alphavirus.
AB  - A sequence of thirty-six nucleotides in the nsP3 gene of Ross River virus (RRV),
      coding for the amino acid sequence HADTVSLDSTVS, was duplicated some time between
      1969 and 1979 coinciding with the appearance of a new lineage of this virus and
      with a major outbreak of Epidemic Polyarthritis among residents of the Pacific
      Islands. This lineage of RRV continues to circulate throughout Australia and both
      earlier lineages, which lacked the duplicated element, now are extinct. Multiple
      copies of several other elements also were observed in this region of the nsP3
      gene in all lineages of RRV. Multiple copies of one of these, coding for the
      amino acid sequence P*P*PR, were detected in the C-terminal region of the nsP3
      protein of all alphaviruses except those of African origin. The fixation of
      duplications and insertions in 3' region of nsP3 genes from all lineages of
      alphaviruses, suggests they provide some fitness advantage.

PMID- 21185050
TI  - Terminal modifications of norovirus P domain resulted in a new type of subviral
      particles, the small P particles.
AB  - The protruding (P) domain of norovirus VP1 is responsible for immune recognition
      and host receptor interaction. Our previous studies have demonstrated that a
      modification of the ends of the P domain affects the conformation and/or function
      of the P protein. An expression of the P domain with or without the hinge, or
      with an additional cysteine at either ends of the P protein resulted in P dimers
      and/or P particles. Here we report a new type of subviral particle, the small P
      particles, through a further modification, either an addition of the flag tag or
      a change of the arginine cluster, at the C-terminus of the cysteine-containing P
      domain. Gel filtration and cryo-EM studies showed that the small P particles are
      tetrahedrons formed by 6 P dimers or 12 P monomers that is half-size of the P
      particles. Fitting of the crystal structure of the P domain into the cryo-EM
      density map of the particle indicated similar conformations of the P dimers as
      those in P particles. The small P particles bind human HBGAs and are
      antigenically reactive similar to their parental VLPs and P particles. These data
      suggest that the C-terminus of the P domain is an important factor in the
      formation of the P particles. Further elucidation of the mechanism of these
      modifications in the P particle formation would be important in structure biology
      and morphogenesis of noroviruses. The small P particles may also be a useful
      alternative in study of norovirus-host interaction and vaccine development for
      noroviruses.

PMID- 21185051
TI  - Investigation of pharmaceuticals in Missouri natural and drinking water using
      high performance liquid chromatography-tandem mass spectrometry.
AB  - A comprehensive method has been developed and validated in two different water
      matrices for the analysis of 16 pharmaceutical compounds using solid phase
      extraction (SPE) of water samples, followed by liquid chromatography coupled with
      tandem mass spectrometry. These 16 compounds include antibiotics, hormones,
      analgesics, stimulants, antiepileptics, and X-ray contrast media. Method
      detection limits (MDLs) that were determined in both reagent water and municipal
      tap water ranged from 0.1 to 9.9 ng/L. Recoveries for most of the compounds were
      comparable to those obtained using U.S. EPA methods. Treated and untreated water
      samples were collected from 31 different water treatment facilities across
      Missouri, in both winter and summer seasons, and analyzed to assess the 16
      pharmaceutical compounds. The results showed that the highest pharmaceutical
      concentrations in untreated water were caffeine, ibuprofen, and acetaminophen, at
      concentrations of 224, 77.2, and 70 ng/L, respectively. Concentrations of
      pharmaceuticals were generally higher during the winter months, as compared to
      those in the summer due, presumably, to smaller water quantities in the winter,
      even though pharmaceutical loadings into the receiving waters were similar for
      both seasons.

PMID- 21185052
TI  - Colloid straining within saturated heterogeneous porous media.
AB  - The transport of 0.46 MUm, 2.94 MUm, 5.1 MUm and 6.06 MUm latex particles in
      heterogeneous porous media prepared from the mixing of 0.78 mm, 0.46 mm and 0.23
      mm quartz sands was investigated through column transport experiments. It was
      observed that the 0.46 MUm particles traveled conservatively within the
      heterogeneous porous media, suggesting that under the experimental conditions
      employed in this research the strong repulsive interactions between the
      negatively charged latex particles and the clean quartz sands led to minimal
      colloid immobilization due to physicochemical filtration. The immobilization of
      the 2.94 MUm, 5.1 MUm and 6.06 MUm latex particles was thus attributed to colloid
      straining. Experimental results showed that the straining of colloidal particles
      within heterogeneous sand mixtures increased when the fraction of finer sands
      increased. The mathematical model that was developed and tested based on results
      obtained using uniform sands (Xu et al., 2006) was found to be able to describe
      colloid straining within heterogeneous porous media. Examination of the
      relationship between the best-fit values of the clean-bed straining rate
      coefficients (k(0)) and the ratio of colloid diameter (d(p)) and sand grain size
      (d(g)) indicated that when number-average sizes were used to represent the size
      of the heterogeneous porous media, there existed a consistent relationship for
      both uniform sands and heterogeneous sand mixtures. Similarly, the use of the
      number-averaged sizes for the heterogeneous porous media produced a uniform
      relationship between the colloid straining capacity term (lambda) and the ratio
      of d(p)/d(g) for all the sand treatments.

PMID- 21185053
TI  - Photocatalytic degradation of benzenesulfonate on colloidal titanium dioxide.
AB  - Titanium dioxide-mediated photocatalyzed degradation of benzenesulfonate (BS) was
      investigated by monitoring chemical oxygen demand (COD), total organic carbon
      (TOC) content, sulfate concentration, pH as well as the absorption and emission
      spectral changes in both argon-saturated and aerated systems. Liquid
      chromatography-mass spectrometry analysis was utilized for the detection of
      intermediates formed during the irradiation in the UVA range (lambda(max) = 350
      nm). The results obtained by these analytical techniques indicate that the
      initial step of degradation is hydroxylation of the starting surfactant,
      resulting in the production of hydroxy- and dihydroxybenzenesulfonates. These
      reactions were accompanied by desulfonation, which increases [H(+)] in both argon
      saturated and aerated systems. In accordance with our previous theoretical
      calculations, the formation of ortho- and meta-hydroxylated derivatives is
      favored in the first step. The main product of the further oxygenation of these
      derivatives was 2,5-dihydroxy-benzesulfonate. No decay of the hydroxy species
      occurred during the 8-h irradiation in the absence of dissolved oxygen. In the
      aerated system much more efficient desulfonation and hydroxylation, moreover, a
      significant decrease of TOC took place at the initial stage. Further
      hydroxylation led to cleavage of the aromatic system, due to the formation of
      polyhydroxy derivatives, followed by ring fission, resulting in the production of
      aldehydes and carboxylic acids. Total mineralization was achieved by the end of
      the 8-h photocatalysis. It has been proved that in this photocatalytic procedure
      the presence of dissolved oxygen is necessary for the cleavage of the aromatic
      ring because hydroxyl radicals photochemically formed in the deaerated system too
      alone are not able to break the C-C bonds.

PMID- 21185054
TI  - Temperature phased anaerobic digestion increases apparent hydrolysis rate for
      waste activated sludge.
AB  - It is well established that waste activated sludge with an extended sludge age is
      inherently slow to degrade with a low extent of degradation. Pre-treatment
      methods can be used prior to anaerobic digestion to improve the efficiency of
      activated sludge digestion. Among these pre-treatment methods, temperature phased
      anaerobic digestion (TPAD) is one promising method with a relatively low energy
      input and capital cost. In this study, an experimental thermophilic (50-70 
      degrees C)-mesophilic system was compared against a control mesophilic-mesophilic
      system. The thermophilic-mesophilic system achieved 41% and 48% volatile solids
      (VS) destruction during pre-treatment of 60  degrees C and 65  degrees C (or 70 
      degrees C) respectively, compared to 37% in the mesophilic-mesophilic TPAD
      system. Solubilisation in the first stage was enhanced during thermophilic pre
      treatment (15% at 50  degrees C and 27% at 60  degrees C, 65  degrees C and 70 
      degrees C) over mesophilic pre-treatment (7%) according to a COD balance. This
      was supported by ammonia-nitrogen measurements. Model based analysis indicated
      that the mechanism for increased performance was due to an increase in hydrolysis
      coefficient under thermophilic pre-treatment of 60  degrees C (0.5 +/- 0.1 d(
      1)), 65  degrees C (0.7 +/- 0.2 d(-1)) and 70  degrees C (0.8 +/- 0.2 d(-1)) over
      mesophilic pre-treatment (0.2 +/- 0.1 d(-1)), and thermophilic pre-treatment at
      50  degrees C (0.12 +/- 0.06 d(-1)).

PMID- 21185055
TI  - Short-term bacterial community composition dynamics in response to accumulation
      and breakdown of Microcystis blooms.
AB  - Short-term bacterial community composition (BCC) dynamics in response to
      accumulation and breakdown of Microcystis blooms were examined by conducting in
      situ mesocosm experiments with varying levels of Microcystis sp. biomass, ranging
      from 15 to 3217 MUg/L as measured by chlorophyll-a concentration in the
      freshwater water column. The BCC was assessed by means of terminal restriction
      fragment length polymorphism (T-RFLP) of 16S ribosomal RNA genes followed by
      cloning and sequencing of selected samples. The results showed that the
      composition of both free-living and particle-attached bacterial communities
      changed during the accumulation and breakdown phases of a Microcystis bloom, and
      differences were also evident with different levels of Microcystis biomass. The
      relative abundance of bacteria affiliated with Micrococcineae and Legionellales
      increased in general after amendment with Microcystis. Significant correlation
      between the relative abundance of Micrococcineae and breakdown of Microcystis
      biomass was also observed. Canonical correspondence analysis (CCA) showed that
      the changes in the free-living and particle-attached bacterial community were
      mostly related to the changes in the concentrations of chlorophyll-a, dissolved
      organic carbon (DOC), dissolved oxygen (DO) and pH, which were mainly induced by
      the breakdown of Microcystis biomass. Overall, our study revealed the following:
      i) accumulation of Microcystis blooms and their breakdown have strong impacts on
      bacterial community composition; ii) there might be saprophytic association
      between Micrococcineae and decomposition of Microcystis biomass; iii) it is
      necessary to reveal potential associations between Legionellales organisms and
      Microcystis blooms in eutrophic freshwater lakes.

PMID- 21185056
TI  - Threshold concentrations of biomass and iron for pressure drop increase in spiral
      wound membrane elements.
AB  - In a model feed channel for spiral-wound membranes the quantitative relationship
      of biomass and iron accumulation with pressure drop development was assessed.
      Biofouling was stimulated by the use of tap water enriched with acetate at a
      range of concentrations (1-1000 MUgCl(-1)). Autopsies were performed to quantify
      biomass concentrations in the fouled feed channel at a range of Normalized
      Pressure Drop increase values (NPD(i)). Active biomass was determined with
      adenosinetriphosphate (ATP) and the concentration of bacterial cells with Total
      Direct Cell count (TDC). Carbohydrates (CH) were measured to include accumulated
      extracellular polymeric substances (EPS). The paired ATP and CH concentrations in
      the biofilm samples were significantly (p<0.001; R(2)=0.62) correlated and both
      parameters were also significantly correlated with NPD(i) (p<0.001). TDC was not
      correlated with the pressure drop in this study. The threshold concentration for
      an NPD(i) of 100% was 3.7 ng ATP cm(-2) and for CH 8.1 MUg CH cm(-2). Both
      parameters are recommended for diagnostic membrane autopsy studies. Iron
      concentrations of 100-400 mg m(-2) accumulated in the biofilm by adsorption were
      not correlated with the observed NPD(i), thus indicating a minor role of Fe
      particulates at these concentrations in fouling of spiral-wound membrane.

PMID- 21185057
TI  - A review of personal care products in the aquatic environment: environmental
      concentrations and toxicity.
AB  - Considerable research has been conducted examining occurrence and effects of
      human use pharmaceuticals in the aquatic environment; however, relatively little
      research has been conducted examining personal care products although they are
      found more often and in higher concentrations than pharmaceuticals. Personal care
      products are continually released into the aquatic environment and are
      biologically active and persistent. This article examines the acute and chronic
      toxicity data available for personal care products and highlights areas of
      concern. Toxicity and environmental data were synergized to develop a preliminary
      hazard assessment in which only triclosan and triclocarban presented any hazard.
      However, numerous PCPs including triclosan, paraben preservatives, and UV filters
      have evidence suggesting endocrine effects in aquatic organisms and thus need to
      be investigated and incorporated in definitive risk assessments. Additional data
      pertaining to environmental concentrations of UV filters and parabens, in vivo
      toxicity data for parabens, and potential for bioaccumulation of PCPs needs to
      obtained to develop definitive aquatic risk assessments.

PMID- 21185058
TI  - Automated evaluation of the effect of ionic liquids on catalase activity.
AB  - An automated assay for the evaluation of the influence of ionic liquids on the
      activity of catalase was developed. The activity and inhibition assays were
      implemented in a sequential injection analysis (SIA) system and intended to
      contribute for the estimation of the toxicity of the tested compounds. The fast
      developed methodology was based on the oxidation of the non-fluorescent probe
      amplex red, in the presence of H2O2, to produce resorufin, a strong fluorescent
      compound. Catalase activity was monitored by the decreased of the fluorescence
      intensity due to the consumption of H2O2 by the enzyme. The activity assays were
      performed in strictly aqueous media and in the presence of increasing
      concentrations of seven commercially available ionic liquids and sodium azide, a
      strong inhibitor of catalase. IC50 values between 0.15 and 2.77 M were obtained
      for the tested compounds, revealing distinct inhibitory effects. This allowed us
      to perform some considerations about the toxicity of the tested cations and
      anions. The developed SIA methodology showed to be robust and exhibited good
      repeatability in all the assay conditions. On the other hand, it proved to be in
      good agreement with the actual concerns of "Green Chemistry" since it involved
      the consumption of less than 200 MUL of reagents and the production of only 1.7
      mL of effluent (per cycle) and at the same time reduced the operator exposure
      resulting in increased environmental and human safety.

PMID- 21185059
TI  - Endocrine disrupting nonyl- and octylphenol in infant food in Germany:
      considerable daily intake of nonylphenol for babies.
AB  - Nonylphenol and octylphenol are persistent endocrine disrupters that are priority
      substances of the European Union Water Framework Directive. Their presence in the
      environment has caused increasing concern about their impact to human health.
      Infants are more sensitive to hormonal impacts of environmental chemicals than
      adults. The results of the present study indicate that nonylphenol is ubiquitous
      in foodstuffs for babies and toddlers commercially available in Germany, while
      octylphenol could only be determined in 80% of all food samples. The daily
      intakes based on consumption studies in MUg nonylphenol kg-1 body weight per day
      for high consumers in the baby category (0.23-0.65 MUg kg-1 bw d-1) were
      relatively high. This could lead to a higher risk especially for babies.

PMID- 21185060
TI  - The arrival and discharge of conjugated estrogens from a range of different
      sewage treatment plants in the UK.
AB  - The occurrence of free and conjugated estrogens was examined in a survey of
      eleven sewage treatment plants (STPs) and their discharge water in the United
      Kingdom using grab sampling. The STPs included trickling filter with and without
      tertiary treatment, and activated sludge with tertiary treatment. For three
      activated sludge plants both influent and effluent samples were compared. For a
      further 8STPs only the effluent was examined. The estrone-3-sulphate, estradiol-3
      sulphate and estriol-3-sulphate concentrations (up to 20 ng L(-1)) were typically
      5-fold that of the respective free estrogen concentration in the effluents. This
      represents a substantial additional 'potential' estrogen load arriving in the
      receiving waters. Estrone-3-glucuronide was found at 9 ng L(-1), estradiol-3
      glucuronide at 7 ng L(-1), and estriol-3-glucuronide at 32 ng L(-1) in sewage
      influent. Except on one occasion, no glucuronide conjugates could be found in the
      effluent. The results suggest in most cases glucuronide conjugates will be
      completely transformed in sewage treatment whilst sulphate conjugates will only
      be partially removed.

PMID- 21185061
TI  - Accumulation and quantitative estimates of airborne lead for a wild plant (Aster
      subulatus).
AB  - Foliar uptake of airborne lead is one of the pathways for Pb accumulation in
      plant organs. However, the approximate contributions of airborne Pb to plant
      organs are still unclear. In the present study, aerosols (nine-stage size
      segregated aerosols and total suspended particulates), a wild plant species
      (Aster subulatus) and the corresponding soils were collected and Pb contents and
      isotopic ratios in these samples were analyzed. Average concentration of Pb was
      96.5 +/- 63.5 ng m(-3) in total suspended particulates (TSP) and 20.4 +/- 5.5 ng
      m(-3) in the fine fractions of size-segregated aerosols (SSA) (<2.1 MUm), higher
      than that in the coarser fractions (>2.1 MUm) (6.38 +/- 3.71 ng m(-3)).
      Enrichment factors show that aerosols and soils suffered from anthropogenic
      inputs and the fine fractions of the size-segregated aerosols enriched more Pb
      than the coarse fractions. The order of Pb contents in A. subulatus was
      roots>leaves>stems. The linear relationship of Pb isotope ratios ((206)Pb/(207)Pb
      and (208)Pb/(206)Pb) among soil, plant and aerosol samples were found. Based on
      the simple binary Pb isotopic model using the mean (206)Pb/(207)Pb ratios in TSP
      and in SSA, the approximate contributions of airborne Pb into plant leaves were
      72.2% and 65.1%, respectively, suggesting that airborne Pb is the most important
      source for the Pb accumulation in leaves. So the combination of Pb isotope
      tracing and the simple binary Pb isotope model can assess the contribution of
      airborne Pb into plant leaves and may be of interest for risk assessment of the
      exposure to airborne Pb contamination.

PMID- 21185062
TI  - Knuckle-walking in Sivapithecus? The combined effects of homology and homoplasy
      with possible implications for pongine dispersals.
AB  - Sivapithecus is a Miocene great ape from South Asia that is orangutan-like
      cranially but is distinctive postcranially. Work by others shows that the humerus
      resembles large terrestrial cercopithecoids proximally and suspensory hominoids
      distally, but most functional interpretations nevertheless situate Sivapithecus
      in an arboreal setting. We present a new quantitative analysis of the
      Sivapithecus capitate and hamate. Though the functional morphology of both bones
      suggests some degree of arboreality, the overall morphology is most similar to
      knuckle-walking African apes. Other features of the Sivapithecus humerus and hind
      limb are also functionally consistent with knuckle-walking, and we suggest that
      this locomotor behavior is a valid alternative functional interpretation of the
      postcranial morphology. We speculate that knuckle-walking in Sivapithecus would
      have evolved independently from African apes, perhaps for similar ecological
      reasons. The discovery of a possible pongine knuckle-walker challenges the
      hypotheses that (1) knuckle-walking evolved only once in hominoids and (2)
      knuckle-walking is too highly specialized to be the positional behavior from
      which human bipedalism evolved. The possibility of knuckle-walking in
      Sivapithecus may help to explain not only the curious combination of characters
      that typify the postcranium but also the unique postcranial morphology of extant
      Pongo. Furthermore, it may clarify the distribution of fossil pongines across
      many ecological zones in Eurasia in the Miocene and Pleistocene, as well as,
      independently, the spread of African apes across a diversity of environments in
      equatorial Africa.

PMID- 21185063
TI  - Rheumatic manifestations of scurvy: a report of three recent cases in a major
      urban center and a review.
AB  - OBJECTIVES: To report 3 cases of scurvy seen in a large urban medical center over
      a 6-month period, referred for evaluation of rheumatologic symptoms and findings
      in the presence of elevated inflammatory markers. The relevant literature is
      reviewed and unusual manifestations highlighted. METHODS: Descriptive case
      reports of 3 patients ultimately diagnosed with scurvy and a review of the
      relevant literature with an emphasis on rheumatologic manifestations (PubMed
      search, 1965 through August 2009). RESULTS: Three patients presented with
      symptoms including fatigue, purpuric rash, synovitis with effusion, anemia, and
      markedly elevated erythrocyte sedimentation rate and C-reactive protein levels.
      One patient presented with severe pulmonary hypertension. Careful nutritional
      history revealed a diet deficient in vitamin C. Examination revealed
      hemarthrosis, skin findings characteristic of scurvy, and deficiency in vitamin C
      on laboratory analysis. Symptoms resolved with vitamin C supplementation.
      Characteristics and frequency of rheumatologic manifestations are reviewed.
      CONCLUSIONS: While scurvy is usually described in poorer countries, individuals
      who have psychiatric disorders, or alcoholics with poor nutrition, it can occur
      even in otherwise normal populations in affluent countries. Such patients often
      present to rheumatologists with rheumatologic symptoms and awareness of the
      disease is necessary to make the proper diagnosis.

PMID- 21185064
TI  - Diffuse calcifications of the spleen: a novel association with systemic lupus
      erythematosus.
AB  - OBJECTIVES: While anatomical and physiological changes in the spleen are reported
      in systemic lupus erythematosus (SLE), a complex autoimmune disease that can
      affect most organ systems, calcifications have not been described as a
      characteristic feature. We report 4 lupus patients with extensive splenic
      calcifications with no apparent cause except for their primary disease. The
      relevant literature on calcifications of the spleen in SLE is also reviewed.
      METHODS: Four lupus patients with extensive splenic calcifications are described,
      identified by radiologists at 2 large urban academic centers. In addition, the
      relevant literature was reviewed (PubMed search 1947 through May 2010) using the
      following terms: "lupus," "spleen," and "calcified," "calcification,"
      "calcifications," or "microcalcifications." English-language case reports and
      series were selected. RESULTS: Four lupus patients were found to have a unique
      pattern of splenic calcifications. The age range was 36 to 73 years. Two of the
      patients were women, and 1 of these had SLE and limited systemic sclerosis. On
      reviewing the literature, 6 additional cases of lupus and splenic calcifications
      were found, 1 of which had pathologic assessment of the spleen on autopsy. The
      incidence of infection was apparently not increased in affected patients.
      CONCLUSIONS: A unique pattern of calcifications of the spleen may be found in
      lupus patients, which can suggest the diagnosis of the underlying connective
      tissue disease. Whether splenic calcification can predispose to hyposplenism
      remains to be determined. While the exact significance of diffuse splenic
      calcification is still unknown, this unique radiologic finding may be a result of
      the disease process itself.

PMID- 21185065
TI  - Percutaneous cryoablation of renal masses: impact of patient selection and
      treatment parameters on outcomes.
AB  - OBJECTIVES: To evaluate whether the trend in patient selection or perioperative
      parameters were associated with treatment outcomes after percutaneous
      cryoablation (PCA) of renal masses. METHODS: We retrospectively analyzed our
      urological oncology database and identified 52 patients treated for a total of 54
      renal masses. Univariate analysis was performed to evaluate whether the variables
      of age, gender, tumor size, number of probes used, total freezing time,
      preoperative creatinine, American Society of Anesthesia class, body mass index,
      or age-adjusted Charlson comorbidity index (CCI) score had an impact on the
      outcomes of treatment failure or the complication rate. RESULTS: During a mean
      follow-up of 21 months, recurrence-free, overall, and disease-specific (based on
      radiographic follow-up and biopsy) survival were 96.2%, 98.1% and 100%,
      respectively. The mean age-adjusted CCI score for patients with postoperative
      complications was 6.5, compared with a mean score of 3.0 in patients without
      postoperative complications (P = .02). The complication rate was also
      significantly higher when a greater number of cryoprobes were used during PCA (P
      < .005). None of the variables analyzed were predictive of treatment failure.
      CONCLUSIONS: Of the pre- and intraoperative variables studied, age-adjusted CCI
      score and number of cryoprobes used were the only variables with predictive value
      for outcomes in regard to treatment failure or complications. As investigators
      continue using cryoablation to treat renal masses, it is important to be able to
      completely and honestly counsel patients regarding the likelihood of
      complications and need for subsequent therapy in the setting of treatment
      failure.

PMID- 21185066
TI  - Automated measurement method and tool of glomerular filtration rate using
      triphasic helical computed tomography images.
AB  - OBJECTIVES: To introduce an automated method to perform computed tomography-based
      glomerular filtration rate (CT GFR) measurement using the 2-point Patlak plot
      technique and triphasic helical CT images. We also evaluated the correlation
      between our automated method and the manual measurement results, as well as the
      results from cystatin C. METHODS: The present study included 25 patients without
      an acute renal disorder. The CT scan protocol consisted of an unenhanced CT
      examination followed by 2 contrast-enhanced CT examinations in the arterial and
      parenchymal phase. Between the noncontrast scan and the arterial scan, 7 dynamic
      scans were obtained to provide more data on the arterial input function. The 2
      point Patlak plot technique was used in the automated and manual measurement
      methods. For each patient, the cystatin C level, determined in blood samples, was
      used as a reference. RESULTS: The correlation between our automated method and
      the cystatin C method in 25 patients was 0.8029 (P < .001). The correlation
      between the manually implemented CT GFR method and the cystatin C method was
      0.8287 (P < .001). A strong correlation (r = .9518, P < .001) was seen between
      the automated and manual measurements using the same model; however, the
      automated process can be finished within 2 minutes. CONCLUSIONS: The automated CT
      GFR measurement method could potentially be used because of its highly improved
      efficiency. Moreover, it would avoid the use of a differential renal nuclear
      study. This would be helpful for predicting the residual GFR after nephrectomy
      and could also be used to predict the residual GFR after partial nephrectomy for
      tumor or stone treatment.

PMID- 21185067
TI  - Expression of gamma-H2AX in endometrial carcinomas: an immunohistochemical study
      with p53.
AB  - OBJECTIVE.: The most frequently mutated gene in human cancer is p53, a gene that
      functions in the checkpoint response to DNA double-strand breaks. gamma-H2AX is a
      marker of activated DNA damage and is overexpressed in many malignancies and
      their precursor lesions. The purpose of this study was to evaluate the
      association between p53 and gamma-H2AX expression and the clinical value of gamma
      H2AX in endometrial carcinoma. METHODS.: We investigated 106 patients with
      primary endometrial carcinoma (type I/endometrioid, n=84; type II/non
      endometrioid, n=20; mixed pattern or other histological types, n=2) who were
      treated at our institution between 1999 and 2009. gamma-H2AX and p53 expression
      were assessed using immunohistochemistry from paraffin-embedded tissue blocks,
      and results were correlated with clinical data. RESULTS.: A strong positive
      correlation was observed between gamma-H2AX and p53 expression (p<0.0001). Like
      p53, gamma-H2AX staining was significantly associated with advanced tumor stage
      (p=0.04), histological grade (p<0.0001), histological type (p<0.0001), and
      vascular space involvement (p=0.05), but not with lymph node involvement (p=0.64)
      and patients' age (p=0.36). In a univariate survival analysis, p53 and gamma-H2AX
      staining were associated with a shortened disease-free and overall survival but
      in the Cox regression analyses both parameters did not serve as independent
      prognostic parameter. CONCLUSIONS.: Our findings suggest that there is a link
      between the p53 dependent cell cycle arrest and gamma-H2AX dependent DNA repair
      pathway in endometrial cancer. Increasing expression levels of gamma-H2AX are
      associated with unfavourable prognostic factors in type I and type II endometrial
      carcinomas.

PMID- 21185068
TI  - Nutrients and foods for the primary prevention of asthma and allergy: systematic
      review and meta-analysis.
AB  - BACKGROUND: Epidemiologic studies suggest that deficiencies of the nutrients
      selenium; zinc; vitamins A, C, D, and E; and low fruit and vegetable intake may
      be associated with the development of asthma and allergic disorders. OBJECTIVES:
      To investigate the evidence that nutrient and food intake modifies the risk of
      children developing allergy. METHODS: We systematically searched 11 databases.
      Studies were critically appraised, and meta-analyses were undertaken. RESULTS: We
      identified 62 eligible reports. There were no randomized controlled trials.
      Studies used cohort (n = 21), case-control (n = 15), or cross-sectional (n = 26)
      designs. All studies were judged to be at moderate to substantial risk of bias.
      Meta-analysis revealed that serum vitamin A was lower in children with asthma
      compared with controls (odds ratio [OR], 0.25; 95% CI, 0.10-0.40). Meta-analyses
      also showed that high maternal dietary vitamin D and E intakes during pregnancy
      were protective for the development of wheezing outcomes (OR, 0.56, 95% CI, 0.42
      0.73; and OR, 0.68, 95% CI, 0.52-0.88, respectively). Adherence to a
      Mediterranean diet was protective for persistent wheeze (OR, 0.22; 95% CI, 0.08
      0.58) and atopy (OR, 0.55; 95% CI, 0.31-0.97). Seventeen of 22 fruit and
      vegetable studies reported beneficial associations with asthma and allergic
      outcomes. Results were not supportive for other allergic outcomes for these
      vitamins or nutrients, or for any outcomes in relation to vitamin C and selenium.
      CONCLUSION: The available epidemiologic evidence is weak but nonetheless
      supportive with respect to vitamins A, D, and E; zinc; fruits and vegetables; and
      a Mediterranean diet for the prevention of asthma. Experimental studies of these
      exposures are now warranted.

PMID- 21185069
TI  - Induced pluripotent stem cells: a novel frontier in the study of human primary
      immunodeficiencies.
AB  - BACKGROUND: The novel ability to epigenetically reprogram somatic cells into
      induced pluripotent stem cells (iPSCs) through the exogenous expression of
      transcription promises to revolutionize the study of human diseases. OBJECTIVE:
      Here we report on the generation of 25 iPSC lines from 6 patients with various
      forms of primary immunodeficiencies (PIDs) affecting adaptive immunity, innate
      immunity, or both. METHODS: Patients' dermal fibroblasts were reprogrammed by
      expression of 4 transcription factors, octamer-binding transcription factor 4
      (OCT4), sex determining region Y-box 2 (SOX2), Krueppel-like factor 4 (KLF4), and
      cellular myelomonocytosis proto-oncogene (cMYC), by using a single excisable
      polycistronic lentiviral vector. RESULTS: iPSCs derived from patients with PIDs
      show a stemness profile that is comparable with that observed in human embryonic
      stem cells. After in vitro differentiation into embryoid bodies, pluripotency of
      the patient-derived iPSC lines was demonstrated by expression of genes
      characteristic of each of the 3 embryonic layers. We have confirmed the patient
      specific origin of the iPSC lines and ascertained maintenance of karyotypic
      integrity. CONCLUSION: By providing a limitless source of diseased stem cells
      that can be differentiated into various cell types in vitro, the repository of
      iPSC lines from patients with PIDs represents a unique resource to investigate
      the pathophysiology of hematopoietic and extrahematopoietic manifestations of
      these diseases and might assist in the development of novel therapeutic
      approaches based on gene correction.

PMID- 21185070
TI  - Structural and immunologic cross-reactivity among filarial and mite tropomyosin:
      implications for the hygiene hypothesis.
AB  - BACKGROUND: The hygiene hypothesis suggests that parasitic infection modulates
      host immune responses and decreases atopy. Other data suggest parasitic
      infections may induce allergic responsiveness. OBJECTIVE: To assess the
      structural and immunologic relationships between the known Dermatophagoides
      pteronyssinus (Der p 10) tropomyosin allergen and filarial tropomyosin of
      Onchocerca volvulus (OvTrop). METHODS: The molecular, structural, and immunologic
      relationships between OvTrop and Der p 10 were compared. Levels of OvTrop
      specific and Der p 10-specific IgE, IgG, and IgG4 in sera of filaria-infected and
      filarial-uninfected D pteronyssinus-atopic individuals were compared, as were the
      responses in nonhuman primates infected with the filarial parasite Loa loa. Cross
      reactivity was compared by antigen-mediated depletion assays and functionality by
      passive basophil sensitization. RESULTS: Filarial and mite tropomyosins were very
      similar, with 72% identity at the amino acid level, and overlapping predicted 3
      dimensional structures. The prevalence of IgE and IgG to Der p 10 was increased
      in filaria-infected individuals compared with uninfected subjects. There was a
      strong correlation between serum levels of Ov- and Der p 10-tropomyosin-specific
      IgE, IgG, and IgG4 (P < .0001; r > 0.79). Preincubation of sera from anti-Der p
      10-positive subjects with OvTrop completely depleted IgE, IgG, and IgG4 anti-Der
      p 10. Basophils sensitized with sera from individuals allergic to Der p 10
      released histamine similarly when triggered with OvTrop or Der p 10. Primates
      experimentally infected with L loa developed IgE that cross-reacted with Der p
      10. CONCLUSION: Filarial infection induces strong cross-reactive antitropomyosin
      antibody responses that may affect sensitization and regulation of allergic
      reactivity.

PMID- 21185071
TI  - The IgG molecule as a biological immune response modifier: mechanisms of action
      of intravenous immune serum globulin in autoimmune and inflammatory disorders.
AB  - Intravenous immune globulin (IVIG) is an important treatment modality in patients
      with humoral or B-cell immune deficiency as replacement therapy. Soon after its
      introduction in the early 1980s for the treatment of patients with immune
      deficiency, IVIG was used in the treatment of children with idiopathic
      thrombocytopenia purpura. Presently, more commercial IVIG is used for the
      treatment of autoimmune and inflammatory disorders than as replacement therapy in
      patients with immune deficiency. Understanding the mechanisms of action of IVIG
      in these autoimmune and inflammatory disorders has occupied investigators over
      the past 3 decades. A number of mechanisms for the immune modulation and anti
      inflammatory actions of IVIG have been described, including Fc receptor blockade,
      inhibition of complement deposition, enhancement of regulatory T cells,
      inhibition or neutralization of cytokines and growth factors, accelerated
      clearance of autoantibodies, modulation of adhesion molecules and cell receptors,
      and activation of regulatory macrophages through the FcgammaRIIb receptor. It can
      now be appreciated that IVIG affects many different pathways to modulate the
      immune and inflammatory response. Further delineation of these pathways might
      lead to new treatment strategies.

PMID- 21185072
TI  - Phenotypic landscape of a bacterial cell.
AB  - The explosion of sequence information in bacteria makes developing high
      throughput, cost-effective approaches to matching genes with phenotypes
      imperative. Using E. coli as proof of principle, we show that combining large
      scale chemical genomics with quantitative fitness measurements provides a high
      quality data set rich in discovery. Probing growth profiles of a mutant library
      in hundreds of conditions in parallel yielded > 10,000 phenotypes that allowed us
      to study gene essentiality, discover leads for gene function and drug action, and
      understand higher-order organization of the bacterial chromosome. We highlight
      new information derived from the study, including insights into a gene involved
      in multiple antibiotic resistance and the synergy between a broadly used
      combinatory antibiotic therapy, trimethoprim and sulfonamides. This data set,
      publicly available at http://ecoliwiki.net/tools/chemgen/, is a valuable resource
      for both the microbiological and bioinformatic communities, as it provides high
      confidence associations between hundreds of annotated and uncharacterized genes
      as well as inferences about the mode of action of several poorly understood
      drugs.

PMID- 21185074
TI  - Slow crack growth and reliability of dental ceramics.
AB  - OBJECTIVE: To determine the slow crack growth (SCG) and Weibull parameters of
      five dental ceramics: a vitreous porcelain (V), a leucite-based porcelain (D), a
      leucite-based glass-ceramic (E1), a lithium disilicate glass-ceramic (E2) and a
      glass-infiltrated alumina composite (IC). METHODS: Eighty disks (O 12 mm * 1.1mm
      thick) of each material were constructed according to manufacturers'
      recommendations and polished. The stress corrosion susceptibility coefficient (n)
      was obtained by dynamic fatigue test, and specimens were tested in biaxial
      flexure at five stress rates immersed in artificial saliva at 37  degrees C.
      Weibull parameters were calculated for the 30 specimens tested at 1 MPa/s in
      artificial saliva at 37  degrees C. The 80 specimens were distributed as follows:
      10 for each stress rate (10(-2), 10(-1), 10(1), 10(2)MPa/s), 10 for inert
      strength (10(2)MPa/s, silicon oil) and 30 for 10(0)MPa/s. Fractographic analysis
      was also performed to investigate the fracture origin. RESULTS: E2 showed the
      lowest slow crack growth susceptibility coefficient (17.2), followed by D (20.4)
      and V (26.3). E1 and IC presented the highest n values (30.1 and 31.1,
      respectively). Porcelain V presented the lowest Weibull modulus (5.2). All other
      materials showed similar Weibull modulus values, ranging from 9.4 to 11.7.
      Fractographic analysis indicated that for porcelain D, glass-ceramics E1 and E2,
      and composite IC crack deflection was the main toughening mechanism.
      SIGNIFICANCE: This study provides a detailed microstructural and slow crack
      growth characterization of widely used dental ceramics. This is important from a
      clinical standpoint to assist the clinician in choosing the best ceramic material
      for each situation as well as predicting its clinical longevity. It also can be
      helpful in developing new materials for dental prostheses.

PMID- 21185073
TI  - Neuromagnetic evidence for a featural distinction of English consonants: sensor-
      and source-space data.
AB  - Speech sounds can be classified on the basis of their underlying articulators or
      on the basis of the acoustic characteristics resulting from particular
      articulatory positions. Research in speech perception suggests that distinctive
      features are based on both articulatory and acoustic information. In recent
      years, neuroelectric and neuromagnetic investigations provided evidence for the
      brain's early sensitivity to distinctive features and their acoustic
      consequences, particularly for place of articulation distinctions. Here, we
      compare English consonants in a Mismatch Field design across two broad and
      distinct places of articulation - labial and coronal - and provide further
      evidence that early evoked auditory responses are sensitive to these features. We
      further add to the findings of asymmetric consonant processing, although we do
      not find support for coronal underspecification. Labial glides (Experiment 1) and
      fricatives (Experiment 2) elicited larger Mismatch responses than their coronal
      counterparts. Interestingly, their M100 dipoles differed along the
      anterior/posterior dimension in the auditory cortex that has previously been
      found to spatially reflect place of articulation differences. Our results are
      discussed with respect to acoustic and articulatory bases of featural speech
      sound classifications and with respect to a model that maps distinctive phonetic
      features onto long-term representations of speech sounds.

PMID- 21185075
TI  - Brief report: The Identity Style Inventory (ISI-3) and the Utrecht-Management of
      Identity Commitments Scale (U-MICS): factor structure, reliability, and
      convergent validity in French-speaking university students.
AB  - The purpose of this study was to evaluate the factor structure and the
      reliability of the French versions of the Identity Style Inventory (ISI-3) and
      the Utrecht-Management of Identity Commitments Scale (U-MICS) in a sample of
      college students (N = 457, 18-25 years old). Confirmatory factor analyses
      confirmed the hypothesized three-factor solution of the ISI-3 identity styles
      (i.e. informational, normative, and diffuse-avoidant styles), the one-factor
      solution of the ISI-3 identity commitment, and the three-factor structure of the
      U-MICS (i.e. commitment, in-depth exploration, and reconsideration of
      commitment). Additionally, theoretically consistent and meaningful associations
      among the ISI-3, U-MICS, and Ego Identity Process Questionnaire (EIPQ) confirmed
      convergent validity. Overall, the results of the present study indicate that the
      French versions of the ISI-3 and UMICS are useful instruments for assessing
      identity styles and processes, and provide additional support to the cross
      cultural validity of these tools.

PMID- 21185076
TI  - Targeted delivery of chlorotoxin-modified DNA-loaded nanoparticles to glioma via
      intravenous administration.
AB  - Gene therapy offers great potential for brain glioma. However, therapeutic genes
      could not reach glioma spontaneously. A glioma-targeting gene delivery system is
      highly desired to transfer exogenous genes throughout the tumor focus. In this
      study, the nanoscopic high-branching dendrimer, polyamidoamine (PAMAM), was
      selected as the main vector. Chlorotoxin (CTX), which has been demonstrated to
      bind specifically to receptor expressed in glioma, was exploited as the targeting
      ligand to conjugate PAMAM via bifunctional polyethyleneglycol (PEG), yielding
      PAMAM-PEG-CTX. The cellular uptake of CTX itself was observed apparently in C6
      glioma cells, almost not in 293 cells. The modification of CTX could
      significantly increase the cellular uptake of vectors and the DNA-loaded
      nanoparticles (NPs) in C6 cells. The in vivo distribution of PAMAM-PEG-CTX/DNA
      NPs in the brain was higher than that of PAMAM/DNA NPs and PAMAM-PEG/DNA NPs.
      Furthermore, the gene expression of PAMAM-PEG-CTX/DNA NPs was higher and broader
      in glioma than that of unmodified and PEG-modified counterparts. The TUNEL
      analysis showed a more wide-extended apoptosis in the CTX-modified group,
      compared to other groups including commercial temozolomide group. The median
      survival time of CTX-modified group and temozolomide group was 59.5 and 49 days,
      respectively, significantly longer than that of other groups. The results
      suggested that CTX could be exploited as a special glioma-targeting ligand, and
      PAMAM-PEG-CTX/DNA NPs is a potential non-viral delivery system for gene therapy
      of glioma via intravenous administration.

PMID- 21185077
TI  - Pregenesys pre-eclampsia markers consensus meeting: What do we require from
      markers, risk assessment and model systems to tailor preventive strategies?
AB  - The Pregenesys Consensus Meeting held in Cambridge on 13 July 2009 was organized
      by the Pregenesys Consortium to review and critically discuss current knowledge
      regarding early markers of preeclampsia, to identify priorities and opportunities
      for future research, to consider issues that may need to be addressed in future
      recommendations and to highlight key issues in cost effectiveness and national
      policies concerning prediction and early screening for the risk of developing
      preeclampsia. This report summarizes the outcome of the Consensus Meeting and
      draws attention to issues for further investigation with specific regard to
      single versus multiple markers, early versus late risk identification, and the
      long-term effects on both maternal and perinatal health and the need to include
      these in any future cost-benefit assessment.

PMID- 21185078
TI  - Positive effects on hematopoiesis in patients with myelodysplastic syndrome
      receiving deferasirox as oral iron chelation therapy: a brief review.
AB  - Iron overload is a frequent consequence in transfusion-dependent myelodysplastic
      syndromes (MDSs), which often requires iron chelation therapy (ICT).
      Interestingly, ICT may sometimes induce a hematologic improvement that leads to
      significant reduction or complete interruption of blood transfusions. This
      phenomenon has been recently described in MDS treated with the new oral chelator
      deferasirox. Here we briefly review the literature about this phenomenon and
      discuss the possible biological mechanisms underlying hematologic effects of
      deferasirox in MDS, starting from a new paradigmatic case in whom both hemoglobin
      level and platelet count improved, inducing transfusion-independence, soon after
      starting the treatment with deferasirox.

PMID- 21185079
TI  - Effects of dissolved organic matter and reduced sulphur on copper bioavailability
      in coastal marine environments.
AB  - Copper-induced toxicity in aqueous systems depends on its speciation and
      bioavailability. Natural organic matter (NOM) and reduced sulphur species can
      complex copper, influencing speciation and decreasing bioavailability. NOM
      composition in estuaries can vary, depending on inputs of terrigenous,
      autochthonous, or wastewater source material. At a molecular level, variability
      in NOM quality potentially results in different extents of copper binding. The
      aims of this study were to measure acute copper EC(50) values in coastal marine
      and estuarine waters, and identify the relationships between total dissolved
      copper EC(50) values and measured water chemistry parameters proportional to NOM
      and reduced sulphur composition. This has implications on the development of
      marine-specific toxicity prediction models. NOM was characterised using dissolved
      organic carbon (DOC) concentration and fluorescence measurements, combined with
      spectral resolution techniques, to quantify humic-, fulvic-, tryptophan-, and
      tyrosine-like fractions. Reduced sulphur was measured by the chromium-reducible
      sulphide (CRS) technique. Acute copper toxicity tests were performed on samples
      expressing extreme DOC, fluorescent terrigenous, autochthonous, and CRS
      concentrations. The results show significant differences in NOM quality,
      independent of DOC concentration. CRS is variable among the samples;
      concentrations ranging from 4 to 40 nM. The toxicity results suggest DOC as a
      very good predictive measure of copper EC(50) in estuaries (r(2)=0.87)
      independent of NOM quality. Furthermore, for filtered samples, CRS exists at
      concentrations that would be saturated with copper at measured EC(50), suggesting
      that while CRS might bind Cu and decrease bioavailability, it does not control
      copper speciation at toxicologically relevant concentrations and therefore is not
      a good predictive measure of copper toxicity in filtered samples.

PMID- 21185080
TI  - Myopia over the lifecourse: prevalence and early life influences in the 1958
      British birth cohort.
AB  - PURPOSE: To investigate the hypothesis that the excessive growth of the eye in
      myopia is associated with general growth and thus influenced by early life
      biological and social factors, and that these associations underlie recent
      secular trends of increasing prevalence and severity of myopia. DESIGN: Cohort
      study. PARTICIPANTS: A total of 2487 randomly selected 44-year-old members of the
      1958 British birth cohort (27% subsample). METHODS: Diverse and detailed
      biological, social, and lifestyle data have been collected by following members
      since birth through a series of clinical examinations or face-to-face interviews
      carried out by trained examiners. At 44 years, cohort members underwent
      autorefraction using the Nikon Retinomax 2 (Nikon Corp., Tokyo, Japan) under non
      cycloplegic conditions. A lifecourse epidemiologic approach, based on 4
      sequential multivariable "life stage" models (preconceptional; prenatal,
      perinatal, and postnatal; childhood; and adult), was used to examine the
      influence of early life biological, social and lifestyle factors, growth
      patterns, and "eye-specific" factors on myopia. MAIN OUTCOME MEASURES: Myopia
      severity (all, mild/moderate: spherical equivalent -0.75 to -5.99 diopters [D];
      severe: >=-6.00 D extreme vs. emmetropia -0.74 to +0.99 D) and myopia onset
      (early [<16 years] vs. later). RESULTS: A total of 1214 individuals (49%; 95%
      confidence interval, 48.8-50.8) were myopic (late onset in 979 [80.6%]). Myopia
      was positively associated with low birthweight for gestational age, gender,
      greater maternal age, higher paternal occupational social class, and maternal
      smoking in early pregnancy. Myopia was independently associated with proxy
      markers of near work and educational performance, with some differences by onset
      and severity. In adults, greater height and higher educational attainment and
      socioeconomic status were associated with myopia. CONCLUSIONS: Trends in the key
      influences on child health and growth identified as novel putative risk factors
      in this study are consistent with global trends of increasing myopia: increasing
      births to older mothers, increasing rates of intrauterine growth retardation and
      survival of affected children, increasing persistence of smoking in pregnancy,
      and changing socioeconomic status. Prospects for prevention of myopia would be
      improved by a paradigm shift in myopia research, with lifecourse and genetic
      epidemiologic approaches applied in tandem in large unselected populations.

PMID- 21185081
TI  - Relationships between early behavioural characteristics and temperament at 6
      years.
AB  - The aim of this study was to analyze the extent to which the relations and the
      stability of the neonatal behaviour and the infant behaviour at both 4 and 12
      months could be used to predict the infant temperament at 6 years. Seventy-two
      full-term, normal-weight, healthy children were followed from 3 days postpartum
      to 6 years. Neonatal behaviour at 3 and 30 days was assessed using the Neonatal
      Behaviour Assessment Scale (NBAS), behaviour at 4 and 12 months was assessed
      using the Infant Behaviour Record (IBR) from the Bayley Scales for Infant
      Development (BSID) and temperament at 6 years was assessed using the Dimensions
      of Temperament Survey-Revised (DOTS-R). Negative and positive affectivity and
      attention were the factors extracted from the behaviours of the IBR. Our results
      showed a low/moderate correlation between neonatal behaviour on the one hand and
      behaviour at 4 and 12 months and temperament at 6 years on the other hand. The
      motor performance, orientation and ANS stability of the neonate at 3 and 30 days
      were predictors of positive and negative affectivity at 4 months. State
      regulation and ANS stability at 3 days were predictors of negative affectivity
      and attention respectively at 12 months. Negative affectivity at 12 months and
      endurance at 30 days were predictors of general activity and
      persistence/attention at 6 years. Also, an inverse relation was found between
      state regulation at 30 days and general activity at 6 years, and a positive
      relation was found between attention at 4 months and persistence/attention at 6
      years. We conclude that neonatal behaviour and behaviour in the first year of
      life are good predictors of temperament at 6 years and that early negative
      affectivity has an important role on infant temperament development.

PMID- 21185082
TI  - Screening for postpartum bipolar disorder: validation of the Mood Disorder
      Questionnaire.
AB  - BACKGROUND: Despite the prevalent nature of postpartum depression in women with
      bipolar disorder, there are currently no screening instruments designed
      specifically for bipolar disorder in the postpartum period. METHODS: Women with
      histories of major depressive disorder or bipolar disorder (type I or II)
      attending an outpatient perinatal clinic were administered the Mood Disorder
      Questionnaire during the first month after delivery. An experienced research
      coordinator, blind to the Mood Disorder Questionnaire results, conducted a face
      to face diagnostic interview using the Structured Clinical Interview for DSM-IV.
      RESULTS: A total of 57 women with bipolar disorder (30 with bipolar II disorder
      and 27 with bipolar I disorder) and 68 women with major depressive disorder
      completed the Mood Disorder Questionnaire between two to four weeks after
      delivery. The traditional scoring criteria yielded a sensitivity of 75.44%
      [95%CI: 62.24%-85.87%] and a specificity of 86.76% [95%CI: 76.36%-93.77%]. The
      optimal cut-off score was eight or more endorsed symptoms without the
      supplementary questions (a sensitivity of 87.72% [95% CI: 76.32%-94.92%] and a
      specificity of 85.29% [95%CI: 74.61%-92.72%]). CONCLUSIONS: The Mood Disorder
      Questionnaire with alternate scoring is a useful screening instrument for bipolar
      disorder in the postpartum period.

PMID- 21185083
TI  - Medial prefrontal cortex and the self in major depression.
AB  - Self-focus (i.e. the process by which one engages oneself in self-referential
      processing) is a core issue in the psychopathology of major depression. The
      cortical midline structures, including the medial prefrontal cortex (MPFC), play
      a key role in self-referential processing in healthy subjects. Four functional
      magnetic resonance imaging studies recently found either an increased or a
      decreased MPFC activation during self-referential processing in depressed
      patients compared to healthy controls. Building on critical differences in
      experimental settings, we argue that these conflicting results are indeed
      consistent with two modes of elevated MPFC activation in major depression. An
      elevated tonic ventral MPFC activation, as uncovered by an event-related design,
      may embody automatic aspects of depressive self-focus, such as attracting
      attention to self-relevant incoming information. An elevated phasic dorsal MPFC
      activation, as uncovered by a block-based design, may embody more strategic
      aspects of depressive self-focus, such as comparing the self with inner
      standards. Additionally, strategic self-focus in depression may recruit the
      anterior cingulate cortex and more lateral regions of the prefrontal cortex. An
      aberrant functional connectivity of the dorsal MPFC may underlie this lack of
      reciprocal inhibition between the cognitive control network and the default mode
      network. Altogether, these results suggest that self-focus in depression may
      emerge as a process competing for brain resources due to a lack of inhibition of
      the default mode network, resulting in detrimental effects on externally-oriented
      cognitive processes. Follow-up studies are warranted to determine the trait vs.
      state nature of these biomarkers and their ability to predict treatment outcome.

PMID- 21185084
TI  - Reliability, minimal detectable changes, practice effects and correlates of the 6
      min walk test in patients with schizophrenia.
AB  - We examined the reproducibility of the 6-min walk test (6 MWT) in patients with
      schizophrenia. Secondary aims were to assess minimal detectable changes and
      practice effects of the 6 MWT and the presence of clinical conditions that might
      interfere. From 71 patients with schizophrenia two trials of the 6 MWT,
      administered within 3 days, were analysed. The intraclass correlation coefficient
      between the two tests was 0.96. The minimal detectable change was 56.2m for men
      and 50.2m for women. Body mass index, daily antipsychotic dose, negative and
      depressive symptoms, resting heart rate, age, smoking behavior and different
      musculoskeletal complaints were all significantly associated with the distance
      walked. The 6 MWT can be recommended for evaluating the functional exercise
      capacity in patients with schizophrenia. Some practice effect could however not
      be excluded.

PMID- 21185085
TI  - The study of social cognition with neuroimaging methods as a means to explore
      future directions of deficit evaluation in schizophrenia?
AB  - This article discusses the important advances in a recent field of science
      dealing with the brain processes implicated in understanding social situations
      and interacting with others. Many behavioral studies on schizophrenia have shown
      the impairment of these processes and their preferential relation with
      disorganization and negative syndromes. Brain imaging is a powerful method to
      identify brain systems participating in these processes in healthy subjects and
      will be used increasingly to study mental disorders such as schizophrenia. A few
      preliminary studies have opened this field of research and allowed for the
      drawing of some limited conclusions. We emphasize the importance of developing an
      integrated neurocognitive framework to account for the multifaceted nature of
      social cognition deficits in schizophrenia. Inspired by contemporary models of
      empathy and social cognition that identify different components such as shared
      representation, mentalizing, self/other distinction, we show how schizophrenia
      affects these components at the behavioral and functional levels. We also outline
      the interest of this model to understand putative abnormalities of contextual
      integration within the area of mentalization. Finally, we discuss how specialized
      measures of brain functions during the performance of these precisely defined
      mental processes might be used as outcome predictors.

PMID- 21185086
TI  - Does perceived social support and parental attitude relate to alexithymia? A
      study in Finnish late adolescents.
AB  - The aim of the present study was to explore the associations of perceived social
      support and parental attitude with alexithymia in a Finnish adolescent population
      sample. Of the initial sample of 935 adolescents, 729 (78%) answered the
      questionnaire and formed the final sample. The mean age of the subjects was 19
      years (range 17-21 years). The 20-item Toronto Alexithymia Scale (TAS-20) was
      used for assessment of alexithymia. Perceived social support from family,
      friends, and significant other people was measured using the Multidimensional
      Scale of Perceived Social Support (MSPSS). Perceived parental care and
      overprotection were assessed using the Parental Bonding Instrument (PBI), and
      separately for mother and father. After controlling for the sociodemographic
      factors, alexithymia was significantly associated with a lower degree of
      experienced social support and higher parental overprotection both in females and
      males. Maternal overprotection was associated (p<0.04) with TAS-20 total score as
      well as the Difficulty Identifying Feelings (DIF) and Difficulty Describing
      Feelings (DDF) subscales. The lack of social support from friends appeared to
      predict alexithymia more strongly than lack of support from family and
      significant other people. Against our hypothesis, maternal and paternal care was
      not directly associated with alexithymic features. This study highlights the
      significance of intrusive and overprotective parental attitudes as a possible
      risk factor for development of alexithymia. However, to assess causality, we need
      longitudinal studies. The results also emphasize the need for further studies to
      establish the significance of peer relationships in the development of
      alexithymia.

PMID- 21185087
TI  - Interaction of the attenuated recombinant rIHNV-Gvhsv GFP virus with macrophages
      from rainbow trout (Oncorhynchus mykiss).
AB  - One of the most important threats to the salmonid aquaculture industry is
      infection caused by novirhabdoviruses such as infectious haematopoietic necrosis
      virus (IHNV) or viral haemorrhagic septicaemia virus (VHSV). Using reverse
      genetics, an avirulent recombinant rIHNV-Gvhsv GFP strain was generated, which
      was able to replicate as effectively as wild type IHNV in a fish cell line and in
      macrophages. Although this recombinant virus induced protective responses against
      IHNV and VHSV, the response did not involve the production of antibodies or
      modulate the expression of some antiviral genes. To determine the immune
      mechanisms underlying the protection conferred by the rIHNV-Gvhsv GFP virus,
      different immune parameters (NO production, respiratory burst activity and the
      induction of apoptosis) were assessed in the macrophage population. The results
      obtained in the present work may indicate that the Nv protein could be important
      in the modulation of NO and ROS production. rIHNV-Gvhsv GFP did not appear to
      have a clear effect on nitric oxide production or apoptosis. However, an
      increased respiratory burst activity (with levels induced by the recombinant
      virus significantly higher than the levels induced by the wild type virus),
      suggests a stimulation of the macrophage population, which could be related to
      the protection against virulent viruses.

PMID- 21185088
TI  - Immunization of sheep with a combination of intimingamma, EspA and EspB decreases
      Escherichia coli O157:H7 shedding.
AB  - Enterohaemorrhagic Escherichia coli O157:H7 are zoonotic pathogens associated
      with haemorrhagic colitis (HC) and the haemolytic uremic syndrome (HUS).
      Ruminants are the main reservoir of this organism and most outbreaks of E. coli
      O157:H7 infections are food borne. Food contamination by ruminant manure has been
      reported as the primary source of human infection, therefore inhibition of E.
      coli O157:H7 colonization and shedding in ruminants could control the risk of
      human exposure to this pathogen. In the present study a vaccine based on the
      translocon proteins EspA and EspB and the outer membrane adhesion factor
      intimingamma significantly reduced faecal shedding of E. coli O157:H7 by orally
      infected sheep. Protection correlates with serum antibody responses to the
      defined antigens and validates the targeting of these colonization factors.
      Whereas vaccination has been described in cattle, this is the first study
      describing a significant decrease in faecal shedding following systemic
      immunization of sheep.

PMID- 21185089
TI  - The assessment of hearing impairment among healthy children in rural and urban
      areas in China.
AB  - OBJECTIVE: To investigate the auditory function of healthy children and provide
      experimental data to protect children's hearing in China. METHODS: Total of 191
      normally growing children (6-12 years old) in Qinling mountain area, the
      pasturing area around Qinghai Lake and Nanjing city were randomly included in
      this study. The whole-frequency auditory thresholds of these children were
      examined. RESULTS: There was significant difference between the boys' and girls'
      auditory thresholds at nearly the whole frequencies in the Qinling area.
      Significant difference was also found between the boys' and girls' auditory
      thresholds at high frequencies and super high frequencies in the pasturing area
      around Qinghai Lake. Overall, the girls' auditory function was much better than
      the boys'. In contrast, there was no significant difference between the boys' and
      girls' auditory thresholds in Nanjing city. The auditory thresholds in high
      frequencies and super high frequencies of the boys in Nanjing city were lower
      than those of the boys in mountain and plateau pasturing areas, while there was
      no significant difference of the girls' auditory thresholds between city and
      rural areas except for a few low frequencies. CONCLUSIONS: Hearing impairment was
      found in Chinese children of rural areas, especially among the boys. Since the
      children in rural areas should have no chance to be exposed to the modern
      industrial noises, it is most likely that the impulse noises from firecrackers
      caused the partial loss of hearings.

PMID- 21185090
TI  - Congenital dacryocystocele: is there a familial predisposition?
AB  - Congenital impatency of the nasolacrimal drainage system is relatively common.
      Dacryocystocele formation is an infrequent variant of such congenital
      nasolacrimal duct obstruction (NLDO). Congenital dacryocystocele typically
      manifests as a mass in the medial canthal region; alternatively the nasolacrimal
      expansion may present solely intranasally as a nasolacrimal duct cyst. Despite
      the relative frequency of congenital NLDO, there have been few reported familial
      cases. We report here two female siblings with congenital dacryocystocele, and
      review the etiology and potential inherited predisposition to this comparatively
      rare entity.

PMID- 21185091
TI  - Altered dipeptidyl peptidase IV and prolyl endopeptidase activities in chronic
      tonsillitis, tonsillar hyperplasia and adenoid hyperplasia.
AB  - OBJECTIVE: To analyse peptidase activities in the removed tonsils and adenoids
      from patients with chronic tonsillitis, tonsillar hyperplasia and adenoid
      hyperplasia. METHODS: We have analyzed 48 tissue samples from patients undergoing
      tonsillectomy and adenoidectomy for chronic tonsillitis, tonsillar hyperplasia or
      adenoid hyperplasia. Tonsillectomy and adenoidectomy samples were collected and
      frozen for later enzyme analysis. The catalytic activity of a pool of peptidases
      (dipeptidyl peptidase IV, prolyl endopeptidase, aminopeptidase A, aminopeptidase
      N, aspartyl aminopeptidase, aminopeptidase B, neutral endopeptidase, pyroglutamyl
      peptidase I, puromycin-sensitive aminopeptidase and cystinyl aminopeptidase) was
      measured fluorometrically. RESULTS: The activity of prolyl endopeptidase was
      higher in tonsillar hyperplasia and adenoid hyperplasia than in chronic
      tonsillitis. On the contrary, dipeptidyl peptidase IV activity was higher in
      chronic tonsillitis than in hypertrophic tissues. When data were stratified by
      age and gender, dipeptidyl peptidase IV was also found to be more active in adult
      and male chronic tonsillitis tissues. Inversely, dipeptidyl peptidase IV activity
      was higher in tissues of females with tonsillar hyperplasia. CONCLUSIONS: These
      data indicate the involvement of dipeptidyl peptidase IV and prolyl endopeptidase
      in the mechanisms underlying chronic tonsillitis, tonsillar hyperplasia and
      adenoid hyperplasia.

PMID- 21185092
TI  - Pharmacogenomic biomarkers: new tools in current and future drug therapy.
AB  - The rapid development of techniques in the area of genome analysis has
      facilitated identification of new pharmacogenomic biomarkers that can provide
      predictive tools for improved drug response and fewer adverse drug reactions.
      Such biomarkers mainly originate from genes encoding drug-metabolizing enzymes,
      drug transporters, drug targets and human leukocyte antigens. Some of these are
      now integrated by the USA Food and Drug Administration and the European Medicines
      Agency into drug label inserts. In this review, we examine the utility and
      mechanistic background of pharmacogenomic biomarkers in several areas of
      medicine, including cancer, infection and cardiovascular disease. We also discuss
      the use of these biomarkers in drug development and address the impact on
      personalized drug prescription, including opportunities and bottlenecks.

PMID- 21185093
TI  - Use of knee height for the estimation of stature in elderly Turkish people and
      their relationship with cardiometabolic risk factors.
AB  - The determination of the approximately truest value in height measurement is
      important in many fields, but it is difficult to perform true measurements,
      especially in the elderly individuals. We planned to investigate the following
      items in geriatric Turkish population: to calculate the decrease in height with
      advancing age by using the standing height measurement and estimated height
      derived from the knee height; to evaluate the significance of difference between
      the two measurement methods in the calculation of body mass index (BMI) and
      waist/height ratio (WHtR); to determine the cut-off value of WHtR according to
      estimated height in elderly individuals. We studied 551 cases aged between 19 and
      97 years. Knee height was measured using a sliding caliper in a sitting position.
      Linear regression analysis was carried out to derive predictive equations for the
      estimation of stature with adults (<= 50 years of age) according to the gender.
      This equation was then used to estimate height among elderly subjects. Of the
      cases, 60.3% were <60 years (mean: 48.75 +/- 7.50); 39.7% of the cases were >60
      years (mean: 69.51 +/- 7.12). Estimated BMI (EBMI) measurements in the females
      and males >60 years were in average 1.23 kg/m(2) and 0.92 kg/m(2) higher than
      their real BMIs, respectively. EBMI measurements in the females <60 years were
      0.32 kg/m(2) higher than their real BMIs (p<0.01). There is a statistically
      significant difference between WHtR in the females of both age groups, and in the
      males >60 years, as compared to our estimated WHtR (EWHtR) measurements (p<0.01).
      The cut-off point of WHtR was 0.61 and 0.58 in the female and male cases of >60
      years in our study, respectively. WHtR seemed to be a better anthropometric index
      that could predict most cardiometabolic risk factors in our study. EWHtR emerged
      to be a better cardiometabolic risk index especially in the elderly group.

PMID- 21185094
TI  - Chronotropic incompetence and survival in chronic heart failure.
AB  - BACKGROUND: Failure of the heart rate to rise normally during an incremental
      exercise test is termed chronotropic incompetence (CI). It is common in patients
      with chronic heart failure (CHF), and we wanted to explore the relation between
      CI and outcome in unselected patients with CHF. METHODS: 411 patients with left
      ventricular systolic dysfunction who underwent cardiopulmonary exercise testing
      (CPET) were included. CI was defined as a failure to achieve 80% of the maximum
      predicted heart rate (HR). A CI index was also calculated: (Peak HR-Rest HR)/(220
      age-Rest HR)*100. Cox regression was used to assess the univariate and
      multivariate relationship between variables and all-cause mortality. Survivors
      were followed for a median of 89months (IQR 62.8-98.6). The majority were male
      (81.4%) with a median age of 67years (IQR 60-73). A subgroup of 266 patients had
      NT-proBNP values. RESULTS: CI was present in 42.3% of the population. The mean CI
      index was 65.7% (SD 41.3%). Patients without CI exercised for longer (510s) and
      had higher peak VO(2) values (21.1mL/kg/min) than those with CI (424 seconds and
      18mL/kg/min). Only peak VO(2), age and beta blocker use were independent
      prognostic variables. In the subset of patients with NT-proBNP available, Log[NT
      proBNP] was the most powerful predictor of mortality followed by peak VO(2) and
      beta blocker use. CONCLUSIONS: Patients with CI had lower exercise time and peak
      VO(2). However CI was not a significant predictor of mortality in patients with
      CHF undergoing CPET.

PMID- 21185096
TI  - Intra- and inter-observer agreement when using a descriptive classification scale
      for clinical assessment of faecal consistency in growing pigs.
AB  - The objective of the current study was to evaluate intra- and inter-observer
      agreement using a descriptive classification scale with four categories,
      descriptive text and pictures for assessment of consistency in faecal samples
      from pigs post weaning. The four consistency categories were score one=firm and
      shaped, score two=soft and shaped, score three=loose and score four=watery. Five
      observers from the same veterinary practice examined 100 faecal samples using the
      scale with four categories. Four of the observers examined the 100 faecal samples
      twice within the same day. Within observers the difference in proportions for the
      individual consistency categories between two examinations was on average 0.04
      (range: 0-0.10). The mean intra-observer agreement was 0.82 (range: 0.72-0.91)
      with a mean kappa value of 0.76 (range: 0.61-0.88). For inter-observer agreement
      overall kappa was 0.64. For the 10 pair-wise comparisons the mean inter-observer
      agreement was 0.73 (range: 0.61-0.90) with a mean kappa value of 0.64 (range:
      0.48-0.87). The difference in proportions for the individual consistency
      categories was on average 0.08 (range: 0-0.17). In conclusion, the agreement
      observed for the descriptive classification scale with four categories,
      descriptive text and pictures may be categorized as a substantial to almost
      perfect intra-observer agreement and a moderate to almost perfect inter-observer
      agreement. However, more objective measures than clinical scales may still be
      needed to improve intra- and inter-observer agreement in research studies.

PMID- 21185095
TI  - Meta-analysis of the combination of warfarin and dual antiplatelet therapy after
      coronary stenting in patients with indications for chronic oral anticoagulation.
AB  - BACKGROUND: The optimal antithrombotic strategy for patients with chronic oral
      anticoagulation undergoing coronary stenting is unknown. Our study conducted a
      meta-analysis of 9 previous trials comparing the safety and efficacy of triple
      antithrombotic regimen (including warfarin, aspirin and clopidogrel) to non
      triple antithrombotic regimens in those patients. METHODS: Two investigators
      independently searched Pubmed, Ovid and Elsevier databases for all reported
      studies, and yielded 9 (of 242 potentially relevant) articles, published before
      July 2009, enrolling 5181 patients, follow-up period ranging from 1 month to 18
      months. Two coauthors independently recorded the data regarding interventions and
      the occurrence of major bleeding, stroke, myocardial infarction and death.
      RESULTS: Patients with triple antithrombotic regimen had significant reduction in
      ischemic stroke (odds ratio [OR] is 0.29, 95% confidence interval [CI] is from
      0.15 to 0.58; and P=0.0004) as compared with dual antiplatelet therapy. While
      there was a two-fold increased risk of major bleeding associated with triple
      antithrombotic regime (OR 2.00, 95% CI 1.41 to 2.83; and P<0.0001). The overall
      incidence of death (OR 1.20, 95% CI 0.63 to 2.27, and P=0.56) and myocardial
      infarction (OR 0.84, 95% CI 0.57 to 1.23; and P=0.38) was comparable between the
      two regimens. CONCLUSION: Our study confirmed the cardiovascular benefits of
      triple antithrombotic regimen by reducing ischemic stroke risk, but also
      demonstrated its increased risk of major bleeding. It poses imperative demands
      for future prospective randomized studies to define the optimal antithrombotic
      regimen in patients requiring chronic anticoagulation undergoing coronary
      stenting.

PMID- 21185097
TI  - Health awareness campaigns and diagnosis rates: evidence from National Breast
      Cancer Awareness Month.
AB  - Awareness campaigns are often used to encourage medical screening that allows for
      early detection of health problems, but much remains unknown about the
      effectiveness of these programs. This paper evaluates whether National Breast
      Cancer Awareness Month (NBCAM) has led to increased diagnosis of breast cancer.
      The analysis examines the number of diagnoses made in November (1 month after
      NBCAM) during years before and after NBCAM was initiated. We find that from 1993
      to 1995, the period when breast cancer advocacy was expanding rapidly into a
      nationwide movement, NBCAM led to an increase in the number of November
      diagnoses. During earlier periods (from the mid-1980s to the early-1990s), when
      breast cancer advocacy was still a nascent grassroots movement, and in later
      periods, when breast cancer advocacy had become a well-established nationwide
      cause, there is little evidence that October NBCAM events had an effect on
      November diagnoses.

PMID- 21185098
TI  - Learning new movement patterns: a study on good and poor writers comparing
      learning conditions emphasizing spatial, timing or abstract characteristics.
AB  - In the earliest stages of motor-skill learning cognitive, visuo-spatial and
      dynamic processes play an important role. Which of these should be addressed
      first when children need to learn a new complex movement sequence? This study
      compares three learning methods in a within-subject design by having 18 good and
      18 poor 8-year-old writers master unfamiliar, letter-like patterns by (1) tracing
      a trajectory on a screen, (2) tracking a moving target (pursuit), and (3)
      performing the pattern using written explicit instructions. Following each 10
      trial learning phase, the children completed a short test phase. Besides errors
      and kinematic data, Dynamic Time Warping (DTW) was used to calculate the
      deviation for each pattern from the ideal shape (DTW-distance). As predicted, the
      number of errors and DTW-distance were very low during the learning phase of the
      tracing and pursuit conditions and higher in the explicit condition. Conversely,
      in the test phase, tracing yielded the highest DTW-distance and the explicit
      condition the lowest DTW-distance and error percentages. The results were
      remarkably similar for the good and poor writers. The poor learning results of
      the tracing condition and the good results of the explicit condition have
      important implications for the teaching of handwriting and remedial therapy.

PMID- 21185099
TI  - Response to Cauraugh, J. H., et al. Bilateral movement training and stroke motor
      recovery progress: a structured review and meta-analysis. Human Movement Science
      (2009), doi: 10.1016/j.humov.2009.09.004.

PMID- 21185100
TI  - Increased dynamic regulation of postural tone through Alexander Technique
      training.
AB  - Gurfinkel and colleagues (2006) recently found that healthy adults dynamically
      modulate postural muscle tone in the body axis during anti-gravity postural
      maintenance and that this modulation is inversely correlated with axial
      stiffness. Our objective in the present study was to investigate whether dynamic
      modulation of axial postural tone can change through training. We examined
      whether teachers of the Alexander Technique (AT), who undergo "long-term" (3
      year) training, have greater modulation of axial postural tone than matched
      control subjects. In addition, we performed a longitudinal study on the effect of
      "short-term" (10-week) AT training on the axial postural tone of individuals with
      low back pain (LBP), since short term AT training has previously been shown to
      reduce LBP. Axial postural tone was quantified by measuring the resistance of the
      neck, trunk and hips to small (+/-10 degrees ), slow (1 degrees /s) torsional
      rotation during stance. Modulation of tone was determined by the torsional
      resistance to rotation (peak-to-peak, phase-advance, and variability of torque)
      and axial muscle activity (EMG). Peak-to-peak torque was lower (~50%), while
      phase-advance and cycle-to-cycle variability were enhanced for AT teachers
      compared to matched control subjects at all levels of the axis. In addition, LBP
      subjects decreased trunk and hip stiffness following short-term AT training
      compared to a control intervention. While changes in static levels of postural
      tone may have contributed to the reduced stiffness observed with the AT, our
      results suggest that dynamic modulation of postural tone can be enhanced through
      long-term training in the AT, which may constitute an important direction for
      therapeutic intervention.

PMID- 21185101
TI  - Comfortable synchronization of cyclic drawing movements with a metronome.
AB  - Continuous circle drawing is considered a paragon of emergent timing, whereas the
      timing of finger tapping is said to be event-based. Synchronization with a
      metronome, however, must to some extent be event-based for both types of
      movement. Because the target events in the movement trajectory are more poorly
      defined in circle drawing than in tapping, circle drawing shows more variable
      asynchronies with a metronome than does tapping. One factor that may have
      contributed to high variability in past studies is that circle size, drawing
      direction, and target point were prescribed and perhaps outside the comfort
      range. In the present study, participants were free to choose most comfortable
      settings of these parameters for two continuously drawn shapes, circles and
      infinity signs, while synchronizing with a regular or intermittently perturbed
      metronome at four different tempi. Results showed that preferred circle sizes
      were generally smaller than in previous studies but tended to increase as tempo
      decreased. Synchronization results were similar for circles and infinity signs,
      and similar to earlier results for circles drawn within a fixed template (Repp &
      Steinman, 2010). Comparison with tapping data still showed drawing to exhibit
      much greater variability and persistence of asynchronies as well as slower phase
      correction in response to phase shifts in the metronome. With comfort level ruled
      out as a factor, these differences can now be attributed more confidently to
      differences in event definition and/or movement dynamics.

PMID- 21185102
TI  - Influence of the farming system and vine variety on yeast communities associated
      with grape berries.
AB  - Wine production in most countries is based on the use of commercial strains
      leading to the colonisation of the wineries by these strains with the consequent
      reduction of autochthonous biodiversity. This implies that wine styles could
      therefore become standardised. The vineyard could be an important source of
      native yeasts of oenological interest. For this reason the objective of this
      study was to compare two agronomic conditions with the aim of preserving yeast
      biodiversity in the vineyard. A three year sampling plan was designed to evaluate
      the influence of different agronomic parameters on the biodiversity of
      fermentative grape yeasts. Thus two vineyards, one organic and one conventional,
      with three different grape varieties (Shiraz, Grenache and Barbera) were chosen.
      In total, 27 samples were collected from both vineyards. Of these, 1080 colonies
      were isolated and a total of 9 species were identified. The strains identified as
      Saccharomyces cerevisiae were genotyped by microsatellite analysis obtaining nine
      different electrophoretic patterns. Classical ecology indexes were used to obtain
      the richness (S), the biodiversity (H') and the dominance (D) of the species
      studied. The results indicated a clear influence on grape associated yeast
      diversity of the phytosanitary treatment used in the vineyard. This is the first
      time that classical ecology indexes have been used to study the ecology of the
      spontaneous fermentation of grape musts and the species Candida sorbosa and
      Pichia toletana have been described in vineyards of the Madrid winegrowing
      region.

PMID- 21185103
TI  - Haemoglobin A1c is superior to fasting glucose in predicting the incidence of
      diabetes over 8 years among Chinese.
AB  - Baseline haemoglobin A1c had a higher standardized hazard ratio, and more optimal
      sensitivity and specificity than fasting glucose in predicting the 8-year
      incidence of diabetes among 530 non-diabetic Chinese from the population-based
      Hong Kong Cardiovascular Risk Factor Prevalence Study.

PMID- 21185104
TI  - Tetanus seroepidemiology and factors influencing immunity status among farmers of
      advanced age.
AB  - OBJECTIVES: Tetanus, which is a vaccine preventable disease, remains a
      significant health concern. The mortality is especially high in elderly and
      farming is a significant risk factor for the disease. This study evaluates the
      serological immunity of tetanus and the related factors, in a farmer population.
      METHODS: This cross-sectional study was carried out in a village located in the
      western part of Turkey. Volunteer farmers over the age of 50 were included in the
      study. The study group was determined by the systematic sampling method. IgG
      class tetanus antibody was measured in sera of each participant. A structured
      questionnaire evaluating the demographic characteristics was completed by the
      investigators. RESULTS: A total of 293 participants (55.3% female, 44.7% male)
      were recruited from March 2010 to June 2010. A serum protective tetanus antitoxin
      level (> 0.1 IU/ml) was detected in 99 out of 293 (33.9%) of participants.
      According to univariate analysis; advancing age, female gender, lower education,
      low monthly income, presence of chronic disease, absent or incomplete vaccination
      history or being unvaccinated in the last ten years were risk factors for
      insufficient tetanus immunity. After multiple logistic regression analysis, up-to
      date vaccination, gender and age were the only factors that remained
      independently associated with immune status (p < 0.001). CONCLUSION: Farmers of
      advancing age are a population at risk for tetanus due to their work environment
      and their absent or incomplete immunization to the disease. Low rates of immunity
      detected highlight the importance to explore strategies in order to improve
      immunization status in this risky population.

PMID- 21185105
TI  - Basic research in evolution and ecology enhances forensics.
AB  - In 2009, the National Research Council recommended that the forensic sciences
      strengthen their grounding in basic empirical research to mitigate against
      criticism and improve accuracy and reliability. For DNA-based identification,
      this goal was achieved under the guidance of the population genetics community.
      This effort resulted in DNA analysis becoming the 'gold standard' of the forensic
      sciences. Elsewhere, we proposed a framework for streamlining research in
      decomposition ecology, which promotes quantitative approaches to collecting and
      applying data to forensic investigations involving decomposing human remains. To
      extend the ecological aspects of this approach, this review focuses on forensic
      entomology, although the framework can be extended to other areas of
      decomposition.

PMID- 21185106
TI  - Wnt signaling in macrophages: augmenting and inhibiting mycobacteria-induced
      inflammatory responses.
AB  - Wnt proteins are secreted, palmitoylated glycoproteins with multiple functions in
      cell proliferation and migration as well as tissue organization. They are best
      known for their role in embryonic development and tissue homeostasis. In the last
      years, Wnt signaling was also shown to be involved in the regulation of
      inflammatory processes: Wnt5a is induced in human macrophages in response to
      mycobacteria and conserved bacterial structures and contributes to the regulation
      of pro-inflammatory cytokines via its receptor Frizzled (Fzd) 5. Wnt5a is also
      induced in other infectious and inflammatory diseases such as tuberculosis,
      sepsis, psoriasis, rheumatoid arthritis and atherosclerosis. In contrast, Wnt3a,
      a ligand of Fzd1, is constitutively expressed by bronchial epithelial cells and
      mediates anti-inflammatory effects on mycobacteria-infected macrophages via the
      Wnt/beta-Catenin signaling pathway. This pathway suppresses the activity of
      GSK3beta, a well known regulator of NF-kappaB-dependent gene transcription. Here
      we review recent data on immunomodulatory activities of Wnt proteins. Additional
      experiments using exogenous Wnt homologs further support the notion that TLR/NF
      kappaB and Wnt signaling are functionally interconnected.

PMID- 21185107
TI  - The production of the sesquiterpene beta-caryophyllene in a transgenic strain of
      the cyanobacterium Synechocystis.
AB  - The plant secondary metabolite, beta-caryophyllene, is a ubiquitous component of
      many plant resins that has traditionally been used in the cosmetics industry to
      provide a woody, spicy aroma to cosmetics and perfumes. Clinical studies have
      shown it to be potentially effective as an antibiotic, anesthetic, and anti
      inflammatory agent. Additionally, there is significant interest in engineering
      phototrophic microorganisms with sesquiterpene synthase genes for the production
      of biofuels. Currently, the isolation of beta-caryophyllene relies on
      purification methods from oleoresins extracted from large amounts of plant
      material. An engineered cyanobacterium platform that produces beta-caryophyllene
      may provide a more sustainable and controllable means of production. To this end,
      the beta-caryophyllene synthase gene (QHS1) from Artemisia annua was stably
      inserted, via double homologous recombination, into the genome of the
      cyanobacterium Synechocystis sp. strain PCC6803. Gene insertion into
      Synechocystis was confirmed through PCR assays and sequencing reactions.
      Transcription and expression of QHS1 were confirmed using RT-PCR, and synthesis
      of beta-caryophyllene was confirmed in the transgenic strain using GC-FID and GC
      MS analysis.

PMID- 21185109
TI  - Synthesis and biological activity of pyrazolothienotetrahydroisoquinoline and
      [1,2,4]triazolo[3,4-a]thienotetrahydroisoquinoline derivatives.
AB  - 1-hydrazino-3-thioxo-5,6,7,8-tetrahydroisoquinoline-4-carbonitrile (3) was
      subjected to react with bifunctional compounds namely: acetylacetone, ethyl
      cyanoacetate, ethyl benzoylactate, diethylmalonate and ethyl acetoacetate to
      produce pyrazololthienotetrahydroisoquinoline derivatives 6-11. Also, heating of
      compound (3) with formic acid afforded triazolothienotetrahydroisoquinoline
      compound 5 which reacted with alpha-halogenated compounds to afford compounds 13a
      e. Compound 13c when heated with triethylorthoformate afforded triazolo
      derivative 14. Also, compound 6 was used for synthesizing compounds 18-20.
      Representative compounds of the synthesized triazolo and
      pyrazolothienotetrahydroisoquinoline products were tested and evaluated as
      antimicrobial agents.

PMID- 21185108
TI  - The Alzheimer's associated 5' region of the SORL1 gene cis regulates SORL1
      transcripts expression.
AB  - SORL1 has been identified as a major contributor to late onset Alzheimer's
      disease (LOAD). We test whether genetic variability in the 5' of SORL1 gene
      modulates the risk to develop LOAD via regulation of SORL1-messenger ribonucleic
      acid (mRNA) expression and splicing. Two brain structures, differentially
      vulnerable to LOAD pathology, were examined in 144 brain samples from 92
      neurologically normal individuals. The temporal cortex, which is more susceptible
      to Alzheimer's pathology, demonstrated ~2-fold increase in SORL1-mRNA levels in
      carriers of the minor alleles at single nucleotide polymorphisms (SNPs),
      rs7945931 and rs2298525, compared with noncarriers. No genetic effect on total
      SORL1-mRNA levels was detected in the frontal cortex. However, rs11600875 minor
      allele was associated with significantly increased levels of exon-2 skipping, but
      only in frontal cortex. No correlation of SORL1-mRNAs expression was found
      between frontal and temporal cortexes. Collectively, these indicate the brain
      region specificity of the genetic regulation of SORL1 expression. Our results
      suggest that genetic regulation of SORL1 expression plays a role in disease risk
      and may be responsible for the reported LOAD associations. Further studies to
      detect the actual pathogenic variant/s are necessary.

PMID- 21185110
TI  - 2-hydroxyisoquinoline-1,3(2H,4H)-diones as inhibitors of HIV-1 integrase and
      reverse transcriptase RNase H domain: influence of the alkylation of position 4.
AB  - We report herein the synthesis of a series of fifteen 2-hydroxyisoquinoline
      1,3(2H,4H)-dione derivatives. Alkyl and arylalkyl groups were introduced on
      position 4 of the basis scaffold. All the compounds presented poor inhibitory
      properties against HIV-1 reverse transcriptase ribonuclease H (RNase H). Four
      compounds inhibited HIV-1 integrase at a low micromolar level. A docking study
      using the later crystallographic data available for PFV integrase allowed us to
      explain the slightly improved integrase inhibitory activities of 4-pentyl and 4
      (3-phenylpropyl)-2-hydroxyisoquinoline-1,3(2H,4H)-diones, when compared to the
      basis scaffold. Physicochemical studies were consistent with 1:1 and 1:2
      (metal/ligand) stoichiometries of the magnesium complexes in solution.
      Unfortunately all tested compounds exhibited high cellular cytotoxicity in cell
      culture which limited their applications as antiviral agents. However these
      identified integrase inhibitors provide a very good basis for the development of
      new hits.

PMID- 21185111
TI  - Developing a framework for critiquing health research: an early evaluation.
AB  - A new framework for critiquing health-related research is presented in this
      article. More commonly used existing frameworks tend to have been formulated
      within the quantitative research paradigm. While frameworks for critiquing
      qualitative research exist, they are often complex and more suited to the needs
      of students engaged in advanced levels of study. The framework presented in this
      article addresses both quantitative and qualitative research within one list of
      questions. It is argued that this assists the 'novice' student of nursing and
      health-related research with learning about the two approaches to research by
      giving consideration to aspects of the research process that are common to both
      approaches and also that differ between quantitative and qualitative research.

PMID- 21185112
TI  - Determinants of fertility and reproductive success after hysteroscopic
      septoplasty for women with unexplained primary infertility: a prospective
      analysis of 88 cases.
AB  - OBJECTIVE: To evaluate prospectively the effect of hysteroscopic septoplasty as
      therapy for unexplained primary infertility in women with uterine septum as a
      sole cause for reproductive failure and to define the factors influencing
      reproductive success. STUDY DESIGN: In a prospective comparative study, we
      enrolled 103 infertile women with uterine septum as a sole cause for reproductive
      failure. They had had unexplained primary infertility >2 years and a follow-up
      >12 months. Uterine anomalies were diagnosed by means of hysterosalpingography
      (HSG) and 2D-transvaginal sonography (TVS) with intrauterine saline infusion.
      Hysteroscopic septoplasty was performed in the early follicular phase. Pregnancy
      rates (PR) according to patient and septum characteristics (septum size) were the
      main outcome measures. RESULTS: Follow-up was complete for 88 patients. The mean
      (+/-SD) age of the patients was 36.1+/-2.1 years. Forty-two patients became
      pregnant (40.7%). The mean (+/-SD) delay in conception was 7.5+/-2.6 months.
      Nearly 80% of the pregnant women conceived spontaneously. Of 44 pregnancies in 42
      women, 36 live newborns were delivered. The PR was significantly higher in women
      <35 years of age or with <3 years of unexplained primary infertility. Moreover,
      in women with a septum size larger than one-half of their uterine length the PR
      was significantly higher than those with septum size <1/2 of their uterus
      (P=.12). CONCLUSION: Fertility and pregnancy after hysteroscopic septoplasty in
      women with unexplained primary infertility and uterine septum as a sole cause for
      reproductive failure seems to depend on patient age, duration of infertility
      before septoplasty, and septum size. Women with a septum size larger than one
      half of their uterine length have a higher chance of successful pregnancy after
      hysteroscopic septoplasty.

PMID- 21185113
TI  - Assessment of ischemia-modified albumin level in patients with recurrent
      pregnancy loss during the first trimester.
AB  - OBJECTIVE: The finding that ischemia-modified albumin (IMA) is increased in pre
      eclamptic pregnancy suggests a role for IMA as a potential biomarker for abnormal
      placental development related to miscarriage. This study was undertaken to
      evaluate IMA levels in women with recurrent pregnancy loss (RPL). STUDY DESIGN:
      This case-control study was performed between March 2008 and September 2009, at
      the Department of Obstetrics and Gynecology of Meram School of Medicine. Serum
      IMA and albumin concentrations were assessed in 43 women with a history of two or
      more unexplained first trimester miscarriages (group 1), and 42 healthy pregnant
      women (group 2) in the first trimester. IMA, adjusted IMA and albumin
      concentrations were compared between the groups. Statistical analysis was
      performed using Student's t-test and Mann-Whitney U test. RESULTS: IMA and
      adjusted IMA levels were significantly higher in women with RPL (1.11+0.08 and
      1.09+0.09, respectively) compared to women in group 2 (0.88+0.10 and 0.88+0.11,
      respectively). Albumin levels in group 1 were significantly lower compared with
      group 2. There was a negative correlation between IMAand albumin levels in each
      group. CONCLUSION: Maternal IMA levels appear to be elevated in women with early
      RPL. This finding may suggest that an abnormally high hypoxic intrauterine
      environment may be associated with abnormal placental development that
      contributes to early miscarriage.

PMID- 21185114
TI  - Understanding stewardship behaviour: factors facilitating and constraining
      private water well stewardship.
AB  - Regulatory frameworks to ensure municipal drinking water safety exist in most
      North American jurisdictions. However, similar protection is rarely provided to
      people reliant on water provided from private wells. In Canada, approximately 4
      million people depend on privately owned, domestic wells for their drinking
      water. Numerous studies have shown that people who rely on private wells for
      their water supplies are at risk from nitrate and bacterial contamination. Given
      the fact that regulations relating to private wells tend to be weak or poorly
      enforced, actions taken by well owners to protect their own drinking water safety
      are extremely important. Drawing on one of the largest and most comprehensive
      surveys of private well owners ever conducted in Canada or elsewhere, this paper
      explores factors that influence well owner stewardship behaviour. Key behaviours
      examined included annual testing of well water and inspection of wells, measures
      to protect water quality, and proper decommissioning of unused wells. A
      geographically-stratified survey, sent to 4950 well owners in Ontario, Canada,
      resulted in an effective response rate of 34% (n = 1567). Logistic regression
      analyses revealed that motivations for well stewardship behaviours included
      reassurance, the perception of problems, and knowledge of the environment.
      Knowing how to perform stewardship behaviours was an important antecedent to
      action. Barriers to stewardship included complacency, inconvenience, ignorance,
      cost, and privacy concerns. To promote stewardship, local initiatives, better
      educational materials, and enforcement through real estate laws are all required.
      Ultimately, drinking water safety for people reliant on private wells is shown to
      be a responsibility shared by governments and private well owners.

PMID- 21185115
TI  - Disease-free survival following salvage cryotherapy for biopsy-proven radio
      recurrent prostate cancer.
AB  - BACKGROUND: The optimum treatment of prostate cancer recurrence following
      radiation therapy (RT) remains controversial due to the lack of long-term data.
      OBJECTIVE: Our aim was to review the survival of patients who underwent salvage
      cryotherapy to the prostate gland for biopsy-proven recurrent prostate cancer and
      establish prognostic indicators. DESIGN, SETTING, AND PARTICIPANTS: A
      retrospective analysis was performed on all patients undergoing salvage
      cryotherapy at an academic urology unit for biopsy-proven locally recurrent
      prostate cancer after RT from 1995 to 2004. Patients' preoperative,
      perioperative, and postoperative data were reviewed and recorded. INTERVENTION:
      Two freeze-thaw cycles of transperineal cryotherapy were performed under
      transrectal ultrasound guidance by a single surgeon. MEASUREMENTS: The primary
      outcome was survival. Secondary outcomes were disease-free survival (DFS),
      metastasis-free survival, and progression to androgen-deprivation therapy.
      RESULTS AND LIMITATIONS: Of 187 patients, 176 had records available for follow-up
      (follow-up rate: 94%). Mean follow-up was 7.46 yr (range: 1-14 yr). Fifty-two
      patients were followed for >10 yr. DFS at 10 yr was 39%. Risk factors for
      recurrence were presalvage prostate-specific antigen (PSA), preradiation, and
      presalvage Gleason score. A PSA nadir >1.0 ng/dl was highly predictive of early
      recurrence. CONCLUSIONS: Salvage cryotherapy led to an acceptable 10-yr DFS.
      Presalvage PSA and Gleason score were the best predictors of disease recurrence.
      A PSA nadir >1 ng/dl following cryotherapy indicated a poor prognosis, and
      recurrence of disease was universal in these patients.

PMID- 21185116
TI  - Does the surgeon really matter? Functional results following radical
      prostatectomy.

PMID- 21185117
TI  - Impact of two-way air flow due to temperature difference on preventing the entry
      of outdoor particles using indoor positive pressure control method.
AB  - Maintaining positive pressure indoors using mechanical ventilation system is a
      popular control method for preventing the entry of outdoor airborne particles.
      The idea is, as long as the supply air flow rate is larger than return air flow
      rate, the pressure inside the ventilated room should be positive since the
      superfluous air flow must exfiltrate from air leakages or other openings of the
      room to the outdoors. Based on experimental and theoretical analyses this paper
      aims to show the impact of two-way air flow due to indoor/outdoor temperature
      difference on preventing the entry of outdoor particles using positive pressure
      control method. The indoor positive pressure control method is effective only
      when the size of the opening area is restricted to a certain level, opening
      degree less than 30 degrees  in this study, due to the two-way air flow effect
      induced by differential temperature. The theoretical model was validated using
      the experimental data. The impacts of two-way air flow due to temperature
      difference and the supply air flow rate were also analyzed using the theoretical
      model as well as experimental data. For real houses, it seems that the idea about
      the positive pressure control method for preventing the entry of outdoor
      particles has a blind side.

PMID- 21185118
TI  - Impact of responder definition on the enriched enrollment randomized withdrawal
      trial design for establishing proof of concept in neuropathic pain.
AB  - The objective of this study was to evaluate how enrichment for responders
      increases assay sensitivity in an enriched enrollment randomized withdrawal
      (EERW) proof-of-concept (POC) study in neuropathic pain. Adults with moderate to
      severe peripheral neuropathic pain entered a 3- to 4-day screening period,
      followed by a 12-day titration to the highest tolerated dose that provided pain
      control (pregabalin 50-200mg t.i.d.), and then a 9-day maintenance period.
      Subjects were stratified as primary responders (?30%), secondary responders (?10%
      to <30%), or nonresponders (<10%) based on decrease in pain intensity and were
      randomized to placebo or pregabalin during the randomized withdrawal period. The
      primary endpoint was mean of average 24-h pain intensity during the last 3days of
      treatment period relative to the 3days before randomization. Time-to-efficacy
      failure was the key secondary endpoint. Other features included not requiring
      discontinuation of current analgesic therapies and blinding investigators to
      study design elements that could contribute to non-treatment-related responses.
      Effect size (ES) (mean treatment difference/SD) was used to measure assay
      sensitivity. Pregabalin-treated subjects (n=52) had significantly less pain than
      those receiving placebo (n=51) (P?.003). Effect size of the primary endpoint was
      0.72 for primary responders and decreased if secondary and nonresponders were
      included in the analysis. The highest ES (1.68) was demonstrated for the endpoint
      time-to-efficacy-failure seen in primary responders with painful diabetic
      neuropathy. The EERW trial design using time-to-efficacy-failure may provide a
      sensitive and efficient method to conduct POC studies of novel therapies in
      patients with neuropathic pain. Enriching a study population with patients who
      have achieved a 30% decrease in pain with an investigational therapy, and using
      time-to-efficacy-failure during the randomized withdrawal phase as the primary
      endpoint, can be used for a proof-of-concept study to optimize assay sensitivity
      and efficiently determine the analgesic potential of a new treatment for
      neuropathic pain.

PMID- 21185120
TI  - Diagnosis and assessment of neuropathic pain: the saga of clinical tools.

PMID- 21185119
TI  - Systematic review of prevalence, correlates, and treatment outcomes for chronic
      non-cancer pain in patients with comorbid substance use disorder.
AB  - Recent data suggest that comorbid substance use disorders (SUDs) are common among
      chronic non-cancer pain (CNCP) patients; however, prevalence rates vary across
      studies and findings are limited regarding treatment options for CNCP patients
      with comorbid SUD. The purpose of this systematic review is to assess the
      prevalence, associated demographic and clinical characteristics, and treatment
      outcomes for CNCP patients with comorbid SUD. We conducted searches from Ovid
      MEDLINE, PsychINFO, and PubMED from 1950 through February 2010 and retrieved the
      references. Thirty-eight studies met inclusion criteria and provided data that
      addressed our key questions. Three to forty-eight percent of CNCP patients have a
      current SUD. There are no demographic or clinical factors that consistently
      differentiate CNCP patients with comorbid SUD from patients without SUD, though
      SUD patients appear to be at greater risk for aberrant medication-related
      behaviors. CNCP patients with SUD are more likely to be prescribed opioid
      medications and at higher doses than CNCP patients without a history of SUD. CNCP
      patients with comorbid SUD do not significantly differ in their responses to
      treatment compared to CNCP patients without SUD, though the quality of this
      evidence is low. Limited data are available to identify predictors of treatment
      outcome. Although clinical experience and research suggests that SUDs are common
      among CNCP patients, only limited data are available to guide clinicians who
      treat this population. Research is needed to increase understanding of the
      prevalence, correlates, and responses to treatment of CNCP patients with comorbid
      SUDs.

PMID- 21185121
TI  - Genetic resistance to natural helminth infections in two chicken layer lines.
AB  - Groups of Lohmann Brown (LB) and Lohmann Selected Leghorn (LSL) hens were reared
      under helminth-free conditions and kept afterwards together in a free range
      system. Mortality rate, body weight development, laying performance and faecal
      egg counts (FEC) were recorded during a 12 month laying period. At the end of the
      laying period, 246 LSL and 197 LB hens were necropsied and worms counted
      following the World Association for the Advancement of Veterinary Parasitology
      (W.A.A.V.P.) guidelines. In addition adult Heterakis gallinarum and Ascaridia
      galli were sexed and measured for length. Significant (P<0.01) differences were
      observed in mortality rates between LSL and LB animals (12.9 vs. 5.7%). LSL hens
      showed significantly (P<0.05) higher FEC when compared with LB hens at almost all
      dates of monitoring. Almost all animals became infected with at least one
      helminth species. The most prevalent species were H. gallinarum, Capillaria spp.
      and A. galli. LB hens showed a significantly (P<0.05) higher average number of
      adult H. gallinarum, Capillaria spp. and tapeworms when compared with LSL
      animals. However, number of adult A. galli was in tendency lower in these
      animals. In total, LB had a significantly (P<0.05) higher worm burden than LSL
      (192.3 vs. 94.3). The estimated heritabilities for total worm burden were 0.23
      (SE+/-0.12) in LSL and 0.75 (SE+/-0.21) in LB, respectively. The number of all
      different helminth species were positively correlated. The sex ratio of H.
      gallinarum and A. galli and the average worm lengths were not significantly
      (P>0.05) different between the genotypes. There was no significant phenotypic
      correlation between body weight and worm burden in LSL, whereas it was the case
      in LB (r=0.17, P<0.05). Based on the estimated heritabilities it is possible to
      select for helminth resistance in both genotypes.

PMID- 21185122
TI  - Cat genotype Tritrichomonas foetus survives passage through the alimentary tract
      of two common slug species.
AB  - Tritrichomonas foetus has recently been recognised as the cause of large bowel
      diarrhoea in cats (feline trichomoniasis), for which the epidemiology is largely
      unknown. We tested whether garden slugs common in Sydney, Australia can pass
      viable T. foetus in their faeces after oral intake. First, Leopard slugs (Limax
      maximus) were offered cat food with 10(4) of T. foetus per gram, 63% (5/8) of
      slugs consumed food with T. foetus and subsequently 20% (1/5) shed T. foetus in
      their faeces. Furthermore, 63% (5/8) and 75% (6/8) of the Leopard slugs and the
      Yellow cellar slugs (Limacus flavus) consumed food with 10(6) of T. foetus per
      gram and subsequently 100% (5/5) and 83% (5/6) shed T. foetus in their faeces,
      respectively. These results suggest that slugs may facilitate passive
      transmission of T. foetus between cats. We speculate that cats may become
      infected with T. foetus should they consume food contaminated with faeces from
      slug(s) infected with T. foetus.

PMID- 21185123
TI  - Noninvasive assessment of burn wound severity using optical technology: a review
      of current and future modalities.
AB  - Clinical examination alone is not always sufficient to determine which burn
      wounds will heal spontaneously and which will require surgical intervention for
      optimal outcome. We present a review of optical modalities currently in clinical
      use and under development to assist burn surgeons in assessing burn wound
      severity, including conventional histology/light microscopy, laser Doppler
      imaging, indocyanine green videoangiography, near-infrared spectroscopy and
      spectral imaging, in vivo capillary microscopy, orthogonal polarization spectral
      imaging, reflectance-mode confocal microscopy, laser speckle imaging, spatial
      frequency domain imaging, photoacoustic microscopy, and polarization-sensitive
      optical coherence tomography.

PMID- 21185124
TI  - Early life stress impairs social recognition due to a blunted response of
      vasopressin release within the septum of adult male rats.
AB  - Early life stress poses a risk for the development of psychopathologies
      characterized by disturbed emotional, social, and cognitive performance. We used
      maternal separation (MS, 3h daily, postnatal days 1-14) to test whether early
      life stress impairs social recognition performance in juvenile (5-week-old) and
      adult (16-week-old) male Wistar rats. Social recognition was tested in the social
      discrimination test and defined by increased investigation by the experimental
      rat towards a novel rat compared with a previously encountered rat. Juvenile
      control and MS rats demonstrated successful social recognition at inter-exposure
      intervals of 30 and 60 min. However, unlike adult control rats, adult MS rats
      failed to discriminate between a previously encountered and a novel rat after 60
      min. The social recognition impairment of adult MS rats was accompanied by a lack
      of a rise in arginine vasopressin (AVP) release within the lateral septum seen
      during social memory acquisition in adult control rats. This blunted response of
      septal AVP release was social stimulus-specific because forced swimming induced a
      rise in septal AVP release in both control and MS rats. Retrodialysis of AVP (1
      MUg/ml, 3.3 MUl/min, 30 min) into the lateral septum during social memory
      acquisition restored social recognition in adult MS rats at the 60-min interval.
      These studies demonstrate that MS impairs social recognition performance in adult
      rats, which is likely caused by blunted septal AVP activation. Impaired social
      recognition may be linked to MS-induced changes in other social behaviors like
      aggression as shown previously.

PMID- 21185125
TI  - Self-assessed parental depressive problems are associated with blunted cortisol
      responses to a social stress test in daughters. The TRAILS Study.
AB  - Depression runs in families and is considered a stress-related disorder. Familial
      risk for depression may be transmitted via deregulated psychophysiological stress
      responses from parent to child. In this study, we examined the association
      between self-assessed lifetime parental depressive problems (PDP) and adolescent
      offspring' cortisol responses to a social stress test. Data were collected as
      part of the third assessment wave of TRAILS (TRacking Adolescents' Individual
      Lives Survey), a large prospective population study of Dutch adolescents. Data of
      330 adolescents (mean age 16.04; 40.9% girls) who participated in a laboratory
      session, including a standardized performance-related social stress task (public
      speaking and mental arithmetic) were examined. Four saliva cortisol samples were
      collected before, during and after the social stress task which were analyzed
      with repeated measures Analysis of Variance. Lifetime parental depressive
      problems were assessed by self-reports from both biological parents. PDP was
      associated with daughter' cortisol responses (F(3,133)=3.90, p=.02), but no
      association was found in sons (F(3,193)=0.27, p=.78). Girls whose parents ever
      experienced depressive symptoms displayed a blunted cortisol response to the
      standardized social stress test, while girls whose parents never had such
      problems displayed the characteristic curvilinear response pattern. This effect
      was not mediated by offspring stress history (age 0-16). Analyses were corrected
      for smoking behaviour and adolescent depressed mood. The fact that PDP were
      measured by self-report questionnaires and did not reflect clinical DSM-IV
      diagnosis could be considered a limitation of the study.

PMID- 21185126
TI  - Nicotine exposure in daily waterpipe smokers and its relation to puff topography.
AB  - Waterpipe tobacco smoking is increasing in popularity worldwide and available
      evidence point to its addictive and harmful potential. This study is conducted to
      assess nicotine exposure in daily waterpipe smokers, and its correlation with
      puff topography parameters. Sixty-one waterpipe tobacco smokers (56 males; mean
      age+/-SD, 30.9+/-9.5years; mean number of weekly waterpipe smoking episodes 7.8+/
      5.7) abstained from smoking for at least 24h, and then smoked tobacco from a
      waterpipe ad libitum in a laboratory setting. During the session puff topography
      parameters were monitored continuously, and pre- and post-smoking expired-air CO
      was measured. Before and after smoking, venous blood was sampled for the
      assessment of plasma nicotine using Gas Chromatography-Mass Spectrometry. The
      average pre- and post-smoking expired-air CO was 4+/-1.7 and 35.5+/-32.7ppm,
      respectively (i.e., a CO boost of 31.5ppm, p<.001). Mean plasma nicotine
      concentration increased from 3.07+/-3.05ng/ml pre-smoking to 15.7+/-8.7ng/ml post
      smoking (p<.001). Plasma nicotine boost was correlated with total session time
      (Pearson correlation coefficient r=.31, p=.04), cumulative puff duration (r=.37,
      p=.01), mean puff duration (r=.34, p=.02), and total smoke inhaled in the session
      (r=.34, p=.02. These data show considerable nicotine exposure in daily waterpipe
      smokers, and that nicotine exposure is a function of waterpipe smoking patterns.

PMID- 21185127
TI  - Adolescent romantic relationships and change in smoking status.
AB  - Although smoking rates have decreased, smoking among adolescents continues to be
      a problem. Previous research has shown the importance of peer influences on
      adolescent smoking behavior but has mostly neglected the impact of adolescent
      romantic relationships. This study examines the influence of romantic
      relationships with smokers and non-smokers on smoking initiation and cessation
      over a one-year period using data from the National Longitudinal Study of
      Adolescent Health (Add Health). For initial non-smokers, we examined whether the
      total length of time in romantic relationships with smokers and non-smokers at
      Wave I, as well as amount of exposure to smoking through romantic partners,
      predicted smoking initiation at Wave II. Among initial regular smokers, we
      examined whether these same relationship characteristics predicted smoking
      cessation at Wave II. These analyses were conducted separately for respondents in
      any type of romantic relationship, as well as just those respondents in close
      romantic relationships. Results indicated that, for close romantic relationships,
      cessation was more likely among smokers with more time in relationships with non
      smoking partners. Greater exposure to smoking through romantic partners at Wave I
      significantly decreased the likelihood of cessation among initial smokers and
      increased the likelihood of initiation among initial non-smokers. For all
      relationships, greater exposure to smoking through romantic partners at Wave I
      significantly reduced the likelihood of cessation. These associations held when
      controlling for best friend smoking, as well as demographic factors and school
      level smoking, suggesting that peer-based smoking programs aimed at adolescents
      should incorporate a focus on romantic relationships.

PMID- 21185128
TI  - Possible involvement of microRNAs (miR-135a*) in heart failure associated with
      25bp deletion in MYBPC3 (cardiac myosin binding protein C) gene.

PMID- 21185129
TI  - Biological resilience of older adults versus frailty.

PMID- 21185130
TI  - Physiological traits and meat quality of pigs as affected by genotype and housing
      system.
AB  - The influence of pig housing system: alternative (bedding with outdoor area, BO)
      vs. conventional (slatted floor, SF) on growth performance, reactivity to pre
      slaughter handling and meat quality was evaluated in two genotypes differing in
      the sire line, Duroc (CD) or synthetic (CS) with 40 pigs/genotype. Animal
      response to housing did not differ between genotypes. BO pigs had higher growth
      rate and feed intake, but similar carcass composition to SF pigs. Levels of
      stress related hormones and plasma metabolites at slaughter were not different
      between BO and SF pigs, suggesting that housing did not influence pig reactivity
      to pre-slaughter handling. Similar (Longissimus lumborum and Biceps femoris) or
      slightly reduced (Semimembranosus) pH values, higher drip, lipid content and
      juiciness were observed in BO compared with SF pork. CD pigs had more tender meat
      than CS. In conclusion, the BO system resulted in higher feed intake, faster
      growth rate, increased intramuscular fat, and improved eating quality in both
      genotypes.

PMID- 21185131
TI  - Expression of proteoglycan versican in in situ breast lesions: relations between
      stromal changes, histotype, and invasion.
AB  - The role of the stromal constituents in the natural history of breast cancers is
      still poorly defined. The aim of the present study was to evaluate the expression
      of proteoglycan versican, a constituent of desmoplastic stroma of invasive
      carcinomas, in preinvasive breast lesions. We selected 41 cases of breast
      carcinoma: 28 pure in situ lesions and 13 invasive lesions with in situ
      associated lesions. The study provided evidence that versican is strongly
      expressed in the perilesional stroma of a subclass of ductal in situ carcinomas,
      and that the extension of versican immunostaining is statistically related to the
      high grade (G3) category (54% of diffuse expressors; p=0.01), and with a comedo
      pattern (67% of diffuse expressors, p=0.003). On the other hand, the expression
      of versican in the cases of classic lobular in situ carcinomas that we selected
      for the study was confined to the anatomical structures that usually contain the
      proteoglycan in adult breast tissues. In our cohort, versican synthesis was found
      to be associated with spindle-shaped elements with myofibroblastic phenotype, as
      in the stroma of invasive carcinoma. These data, taken together with evidence
      from previous studies on proteins strongly related to versican, suggest that
      various histotypes of breast in situ carcinomas could follow different pathways
      of epithelial stromal interactions. In particular a category of in situ lesions
      shows constituents of desmoplastic stroma before the manifestation of the
      morphological signs of invasion. Study of the connective tissue modifications
      that trigger the pivotal phase of invasion could provide new prospects in
      oncology.

PMID- 21185132
TI  - [Impact of elective single embryo transfer criteria on the twin pregnancy rate in
      a French population].
AB  - To reduce the twin pregnancy rate and their morbidity, several recommendations
      have been proposed to practice the "elective single embryo transfer" in a
      selected population. We decided to apply the criteria that were proposed in five
      articles from the literature to our population to evaluate the percentage of our
      population concerned and the impact on our twin pregnancy rate. The result is
      that these criteria only concern 2,4 to 10,8% of our population with a minor
      reduction of our twin pregnancy rate with a potential lake of chance concerning
      the pregnancy rate. We should study others possibilities than the population's
      criteria to reduce the number of embryo transferred.

PMID- 21185133
TI  - [Termination of pregnancy and intra-uterine fetal death after 14 weeks of
      pregnancy: Which protocol for induction of labour in 2010?].
AB  - The induction of labour for intra-uterine fetal death (IUFD) and termination of
      pregnancy (TOP) is a common obstetrical situation. The management of these
      specific inductions has improved. OBJECTIVES: Define a protocol that meets the
      several constraints of security, efficiency and cost for labor induction for IUFD
      and TOP. MATERIALS AND METHODS: Review. RESULTS: The protocol chosen uses the
      mifepristone 200mg by oral way on the first day for cervical preparation,
      completed by placing laminaria tents the evening of the 2nd day if the membranes
      are unreachable. On the 3rd day, in the birth room, the labor starts under
      analgesia, by using misoprostol 400 MUg through vaginal way every 3 hours.
      Specific situations such as scarred uterus need modifications. CONCLUSION: Many
      protocols are described in the literature, they differ in their molecules, their
      dosages and their associations. This review offers a protocol that meets the
      announced objectives.

PMID- 21185134
TI  - Clinical and microbial efficacy of antimicrobial treatments of experimental avian
      colibacillosis.
AB  - The clinical and microbial efficacy of antimicrobial treatments of avian
      colibacillosis was studied, using an experimental model on chickens previously
      inoculated with multiresistant commensal Escherichia coli strains. One E. coli
      with pMG252 plasmid containing bla(FOX5) and qnrA1 genes and another E. coli with
      pMG298 plasmid containing bla(CTX-M15) and qnrB1 genes were first orally
      inoculated to chickens Both isolates were also resistant to chloramphenicol,
      sulphamethoxazole, trimethoprim, streptomycin, gentamicin, kanamycin, and
      tetracycline. The birds were then experimentally infected with an avian
      pathogenic E. coli (APEC), via the air sac. Treatments (oxytetracycline (OTC),
      trimethoprim-sulfadimethoxin (SXT), amoxicillin (AMX) or enrofloxacin (ENR) were
      then offered at the therapeutic doses. Symptoms, lesions in dead or sacrificed
      birds, and isolation and characterization of APEC from internal organs were
      studied. Results showed that OTC, SXT or ENR treatments could control the
      pathology. AMX worsened the disease, possibly due to endotoxin shock. All APEC re
      isolated from internal organs showed the same antimicrobial susceptibility as the
      APEC inoculated strain, except for one APEC isolate from an infected OTC-treated
      bird, which acquired tetracycline resistance only, and one APEC isolate recovered
      from the air sacs of a chicken in the infected SXT-treated group, which acquired
      the pMG252 plasmid and became multi-resistant. Thus three antimicrobials could
      control the disease but the experimental model enabled, to our knowledge, the
      first observation of plasmid transfer from a bacterium of the intestinal tract to
      a pathogenic isolate from the respiratory tract.

PMID- 21185135
TI  - Management of menopausal symptoms in breast cancer patients.
AB  - In breast cancer patients, menopausal symptoms such as hot flashes, urogenital
      problems, musculoskeletal symptoms and cognitive dysfunction are common,
      regardless of age at diagnosis. They affect quality of life and systemic therapy
      will worsen this. Endocrine and/or chemotherapy may induce temporary or permanent
      ovarian failure and can exacerbate these symptoms. Hormone therapy (HT) has been
      studied in breast cancer survivors, but safety has been questioned. The HABITS
      trial investigating estrogen-based HT, as well as the LIBERATE trial
      investigating tibolone, found a reduction in disease-free survival for those
      treated. Alternative strategies are needed, as menopause symptoms may reduce
      compliance with breast cancer treatments. This article reviews recently published
      strategies to tackle menopausal problems in breast cancer patients.
      Antidepressants may help with hot flashes. Acupuncture and hypnosis can also be
      used but the evidence is conflicting. For urogenital problems vaginal
      moisturizers or topical estrogens can be employed. A musculoskeletal syndrome
      induced by aromatase inhibitors (AIs) is frequently encountered and currently
      there are no effective treatment strategies. Bisphosphonates reduce AI-induced
      bone resorption and can also increase disease-free and overall survival. Standard
      dose endocrine and chemotherapy are associated with a decline in cognitive
      function.

PMID- 21185136
TI  - A novel skull registration based on global and local deformations for
      craniofacial reconstruction.
AB  - Craniofacial reconstruction is important in forensic identification. It aims to
      estimate a facial appearance for human skeletal remains using the relationship
      between the soft tissue and the underlying bone structure. Various computerized
      methods have been developed in recent decades. An effective way is to deform a
      reference skull to the discovered skull, and then apply the same deformation to
      the skin associated with the reference skull to provide an approximate face for
      the discovered skull. For this method, the better the two skulls match each
      other, the more face-like the reconstructed skin surface will be. In this paper,
      we present a novel skull registration method that can match the two skulls
      closely, so as to improve the accuracy of the reconstruction. It combines both
      global and local deformations. A generic thin-plate spline (TPS)-based
      deformation, which is global, is applied first to roughly align the two skulls
      based on two groups of manually defined landmarks. Afterwards, the two skulls are
      largely matched, except some regions, on which some new landmarks are
      automatically marked. A compact support radial basis functions (CSRBF)-based
      deformation, which is local, will then be performed on these regions to adjust
      the initial alignment of the two skulls. Such adjustment can be repeatedly
      implemented until the two skulls have optimal alignment. In addition, all the
      skulls and face involved in the registration are represented by their single
      outer surfaces to facilitate the reconstruction procedure. The experiments
      demonstrate that our method can create a plausible face even when the reference
      skull is very different from the discovered skull. As a result, we can make full
      use of our database to provide multiple estimates for a principle components
      analysis (PCA) for the final reconstruction.

PMID- 21185137
TI  - Adipocere: what is known after over two centuries of research.
AB  - This paper reviews over two centuries of research focusing on various issues
      relating to adipocere. Adipocere is a crumbly, soap-like postmortem product that
      forms from soft tissue in a variety of environments. The timing of the formation
      and degradation of adipocere depends largely on the environmental circumstances.
      Once formed, adipocere can persist for hundreds of years, acting as a
      preservative. In this way, some define it as a process of mummification. This
      type of persistence can be useful in a forensic context as it can preserve
      evidence. Sustained interest in adipocere prompted many investigations into the
      composition and conditions of formation. More recent investigations, aided by
      technological advances, build upon the knowledge gained from prior studies as
      well as delve into the chemical composition of adipocere. This in turn provides
      new information on detection and documentation of constituent substances.

PMID- 21185138
TI  - Filling the evidence gap: how can we improve the outcome of neonatal
      encephalopathy in the next 10 years?
AB  - Neonatal encephalopathy associated with perinatal hypoxia-ischaemia is one of the
      most common causes of death and permanent disability worldwide. However, of a
      wide range of "experimentally neuroprotective treatments" invented so far, only
      therapeutic hypothermia has been promoted into a standard clinical practice. Such
      a wide gap in the efficacy of neuroprotective treatments between the experimental
      setting and clinical practice may be attributed to the strategic flaw in
      translating basic knowledge into clinical care. When previous clinical studies
      are carefully reviewed, one may notice that few therapeutic options were chosen
      based on their track records in experimental studies; protective effects of some
      drugs had been assumed only based on their pharmacokinetics in adult species;
      several therapies were chosen merely because clinicians were familiar to these
      treatments for other purpose; some other therapies were imported too
      preliminarily from laboratory to clinical practice, potentially ignoring the
      difference in physiological and pathological backgrounds between rodent models
      and human patients. When further clinical trials are planned, it is important to
      ask whether (i) the treatment is supported by pharmacokinetics specific to
      immature brain, and (ii) the neuroprotective effect of the treatment has
      consistently been demonstrated using clinically relevant models and study
      designs. The use of translational large animal models allows the practical
      simulation and fine-tuning of clinical protocols, which may further assist
      successful translation of basic knowledge. In addition to the effort to develop
      alternative therapeutic options, it is important to maximise the effect of the
      current only neuroprotective option, or therapeutic hypothermia. Independent
      variables which influence the efficacy of hypothermia have to be elucidated to
      improve its therapeutic protocol, and to increase the number of patients who will
      benefit from this treatment.

PMID- 21185139
TI  - Lymphocytosis as a predictor of poor response to  treatment of hepatitis C.
AB  - BACKGROUND/AIMS: Identification of factors predicting response to therapy is
      critical in the management of hepatitis C. This study assessed significance of
      lymphocytosis as a predictor of sustained virological response (SVR). METHODS:
      Retrospective analysis of lymphocytosis and its correlation with virologic
      response was performed in 110 subjects with chronic HCV infection, who underwent
      interferon based therapy. Lymphocytosis was defined as ratio of lymphocytes to
      neutrophils (L/N) above 0.6. L/N ratios were calculated to avoid the impact of
      hypersplenism and constitutional leukopenia seen in African Americans (AA).
      RESULTS: At baseline, L/N of HCV subjects (0.86) as compared to Hepatitis B
      controls (0.56) was significantly higher (P < 0.01). More AA HCV subjects (81.8%)
      had lymphocytosis at baseline when compared to Caucasian Americans subjects with
      HCV (37.9%) or AA controls (39.4%). Nonresponders had a higher frequency of
      lymphocytosis at baseline compared to subjects that achieved SVR (61.4% vs.
      36.0%, p<0.05). More HCV subjects without lymphocytosis at baseline achieved SVR
      (33.3%) compared to HCV subjects with lymphocytosis (15%). At week 12 of therapy,
      nonresponders had higher L/N (1.02 vs. 0.86) and frequency of lymphocytosis (73%
      vs. 48%) compared to subjects that achieved SVR (p<0.05 for both). Only 17.2% of
      subjects with lymphocytosis at 12 weeks achieved SVR compared to 37.5% without
      lymphocytosis (p < 0.05). All responders exhibited significant normalization of
      lymphocytosis after treatment. CONCLUSIONS: HCV induces lymphocytosis, especially
      in AA, and is associated with lower rate of SVR. Furthermore, lymphocytosis may
      serve as an inexpensive pre-treatment tool to predict poor virologic response to
      HCV therapy.

PMID- 21185141
TI  - Dual Energy CT lung perfusion imaging--correlation with SPECT/CT.
AB  - OBJECTIVE: Aims were (1) to determine the diagnostic accuracy of Dual Energy CT
      (DECT) in the detection of perfusion defects and (2) to evaluate the potential of
      DECT to improve the sensitivity for PE. METHODS: 15 patients underwent Dual
      Energy pulmonary CT angiography (DE CTPA) and a combination of lung perfusion
      SPECT/CT and ventilation scintigraphy. CTPA and DE iodine distribution maps as
      well as perfusion SPECT/CT and inhalation scintigrams were reviewed for pulmonary
      embolism (PE) diagnosis. DECT and SPECT perfusion images were assessed regarding
      localization and extent of perfusion defects. Diagnostic accuracy of DE iodine
      (perfusion) maps was determined with reference to SPECT/CT. Diagnostic accuracies
      for PE detection of DECT and of SPECT/CT with ventilation scintigraphy were
      calculated with reference to the consensus reading of all modalities. RESULTS: DE
      CTPA had a sensitivity/specificity of 100%/100% for acute PE, while the
      combination of SPECT/CT and ventilation scintigraphy had a
      sensitivity/specificity of 85.7%/87.5%. For perfusion defects, DECT iodine maps
      had a sensitivity/specificity of 76.7% and 98.2%. CONCLUSION: DECT is able to
      identify pulmonary perfusion defects with good accuracy. This technique may
      potentially enhance the diagnostic accuracy in the assessment of PE.

PMID- 21185142
TI  - Crohn's disease: CT enterography manifestations before and after treatment.
AB  - PURPOSE: The purpose of this study was to determine whether CT enterography (CTE)
      changes of Crohn's disease (CD) after treatment correlated with clinical
      remission. MATERIALS AND METHODS: We retrospectively studied 50 known CD patients
      (male: 35; female: 15) with clinical remission in a period of 3 years (2005
      2008). CD was diagnosed by clinical, enteroscopic and pathologic manifestations.
      Clinical remission was identified by experienced gastroenterologists using the
      combing criteria of clinical, endoscopy and laboratory tests. First CTE and
      endoscopy exams were performed during their first hospitalization in our hospital
      meanwhile CD diagnosis was made during that time. Repeated CTE and endoscopy
      exams were done after treatment. CTE findings were determined by two experienced
      radiologists with double-blind approach. Each patient was analyzed for the CTE
      parameters including bowel wall attenuation, bowel wall thickening (>3mm), bowel
      wall thickening types (type A: multilayered mural stratification; type B: two
      layers with strong mucosal enhancement and prominent low-density submucosa; type
      C: two layers without strong mucosal enhancement; type D: homogeneous
      enhancement) comb sign, luminal stenosis (mild: luminal diameter 2-3 cm;
      moderate: luminal diameter 1-2 cm; severe: luminal diameter<1cm) and the presence
      of extraenteric complications (such as fistulas and abscess). All the
      quantitative parameters were measured three times by each review. RESULTS: After
      treatment, bowel wall thickening was attenuated in 88% of CD patients. Thickness
      of bowel wall was decreased from 8.8 +/- 2.8mm to 6.4 +/- 1.9 mm (P<0.001). CT
      value of bowel wall in portal stage was also declined from 90.0 +/- 15.4 (HU) to
      73.4 +/- 14.2 (HU (P<0.001). The percentage of patients with type A or B bowel
      wall thickening was decreased from 78.7% to 35.4%, while those with type C or D
      thickening was increased from 21.2% to 64.6% (P<0.001). The percentage of
      patients with comb sign was decreased from 88% to 60% (P=0.001). The percentage
      of patients with moderate or severe luminal stenosis was reduced from 74% to 32%
      (P<0.001). The ROC (receiver operating characteristic) analysis showed bowel wall
      attenuation (A(z)=0.89) and bowel wall thickness (A(z)=0.81) were the two best
      parameters to predict disease activity, and combining of these two values was
      better than using them solely (kappa=0.71, P<0.001). The bowel wall attenuation
      (OR=9.56, P<0.001) and bowel wall thickness (OR=3.32, P=0.001) were significantly
      correlated with the disease activity in the following logistic regression
      analysis. CONCLUSION: Therapeutic effect of CD and disease activity can be
      properly evaluated by CTE.

PMID- 21185144
TI  - Toward a new methodological paradigm for testing theories of health behavior and
      health behavior change.
AB  - OBJECTIVE: Traditional theory testing commonly applies cross-sectional (and
      occasionally longitudinal) survey research to test health behavior theory. Since
      such correlational research cannot demonstrate causality, a number of researchers
      have called for the increased use of experimental methods for theory testing.
      METHODS: We introduce the multi-methodological theory-testing (MMTT) framework
      for testing health behavior theory. RESULTS: The MMTT framework introduces a set
      of principles that broaden the perspective of how we view evidence for health
      behavior theory. It suggests that while correlational survey research designs
      represent one method of testing theory, the weaknesses of this approach demand
      that complementary approaches be applied. Such approaches include randomized lab
      and field experiments, mediation analysis of theory-based interventions, and meta
      analysis. CONCLUSION: These alternative approaches to theory testing can
      demonstrate causality in a much more robust way than is possible with
      correlational survey research methods. Such approaches should thus be
      increasingly applied in order to more completely and rigorously test health
      behavior theory. PRACTICE IMPLICATIONS: Greater application of research derived
      from the MMTT may lead researchers to refine and modify theory and ultimately
      make theory more valuable to practitioners.

PMID- 21185143
TI  - Arcobacter molluscorum sp. nov., a new species isolated from shellfish.
AB  - Nineteen bacteria isolates recovered from shellfish samples (mussels and oysters)
      showed a new and specific 16S rDNA-RFLP pattern with an Arcobacter identification
      method designed to recognize all species described up to 2008. These results
      suggested that they could belong to a new species. ERIC-PCR revealed that the 19
      isolates belonged to 3 different strains. The sequence of the 16S rRNA gene of a
      representative strain (F98-3(T)) showed 97.6% similarity with the closest species
      Arcobacter marinus followed by Arcobacter halophilus (95.6%) and Arcobacter
      mytili (94.7%). The phylogenetic analysis with the16S rRNA, rpoB, gyrB and hsp60
      genes placed the shellfish strains within the same cluster as the three species
      mentioned (also isolated from saline habitats) but they formed an independent
      phylogenetic line. The DDH results between strain F98-3(T) and A. marinus
      (54.8%+/-1.05), confirmed that it represents a new species. Several biochemical
      tests differentiated the shellfish isolates from all other Arcobacter species.
      Although the new species was different from A. mytili, they shared not only the
      same habitat (mussels) but also the characteristic of being so far the only
      Arcobacter species that are simultaneously negative for urea and indoxyl acetate
      hydrolysis. All results supported the classification of the shellfish strains as
      a new species, for which the name Arcobacter molluscorum sp. nov. with the type
      strain F98-3(T) is proposed (=CECT 7696(T)=LMG 25693(T)).

PMID- 21185145
TI  - Clinical factors affecting inspired gas humidification and oral dryness during
      noninvasive ventilation.
AB  - PURPOSE: Oral dryness is a common complication during noninvasive ventilation
      (NIV). We measured the oral dryness of patients and performed a bench study to
      investigate factors related to humidification during NIV. MATERIALS AND METHODS:
      Patients were randomly assigned into 2 groups: medium (Med group) and maximum
      (Max group) heated humidifier (HH) settings. Oral moistness was measured using an
      oral moisture-checking device, and the feeling of oral dryness was evaluated
      using a 0 to 10 numerical rating scale (NRS) at 0, 12, and 24 hours from the
      beginning of NIV and at 12 and 24 hours after NIV was discontinued. A bench study
      was performed to assess the effects of positive end-expiratory pressure (PEEP),
      the fraction of inspired oxygen (F(I)O(2)), and air leaks on absolute humidity.
      We evaluated 3 HH settings: no HH, HH at the medium setting, and HH at the
      maximum setting. The temperature in the outlet chamber was 31 degrees C to 32
      degrees C for the medium HH setting and 38 degrees C to 41 degrees C for the
      maximum HH setting. RESULTS: In the clinical study, 12 patients were assigned to
      the Med group and 11 to the Max group. In the Med group, oral moistness decreased
      and NRS increased at 12 and 24 hours compared with 0 hours (P < .05). In the Max
      group, neither the oral moistness nor the NRS changed throughout the study
      period, whereas in the bench study, high F(I)O(2), high PEEP, and air leak
      decreased the absolute humidity for both HH settings (P < .01). However, it is
      not clear to what extent these factors affected the patients' oral dryness
      because the ranges of F(I)O(2) and PEEP were narrow. CONCLUSIONS: Oral dryness
      was a common problem in our patients. The HH setting significantly affected
      humidification and oral dryness during NIV.

PMID- 21185146
TI  - Cardiovascular manifestations of acute pancreatitis.
AB  - Acute pancreatitis (AP) is an acute inflammatory process of the pancreas that is
      associated with variable involvement of pancreatic/peripancreatic tissue and one
      or more organ systems in varying degrees. Among the multiple organ system
      dysfunctions in severe AP, cardiovascular and/or pulmonary manifestations are
      frequent. The cardiovascular system may be affected alone or with other organ
      systems in all stages of AP. Abnormalities of cardiac rhythm, contractility, and
      vasomotor tone of peripheral vessels are common cardiovascular manifestations.
      The pathogenetic factors of cardiac manifestations include hypovolemia and
      metabolic disturbances (eg, hyperkalemia, hypomagnesemia, and hypophosphatemia).
      Clinically, patients present with hypotension, tachycardia, and signs of systemic
      inflammatory response syndrome (high cardiac index, significant pulmonary
      shunting, decreased systemic vascular resistance, and decreased myocardial
      contractility). Approximately 50% of patients with AP have electrocardiographic
      changes, most commonly T-wave flattening and ST-segment depression. Many of the
      cardiac manifestations in AP are reversible with appropriate management. In AP,
      early onset of either multi-organ dysfunction or a sustained single-organ
      dysfunction is associated with poor outcome. This review highlights cardiac
      manifestations of AP relevant to clinical practice.

PMID- 21185147
TI  - Edgar Van Nuys Allen: the test was only the beginning.

PMID- 21185148
TI  - Epicardial fat: an additional measurement for subclinical atherosclerosis and
      cardiovascular risk stratification?
AB  - BACKGROUND: The value of epicardial adipose tissue (EAT) thickness as determined
      by echocardiography in cardiovascular risk assessment is not well understood. The
      aim of this study was to determine the associations between EAT thickness and
      Framingham risk score, carotid intima media thickness, carotid artery plaque, and
      computed tomographic coronary calcium score in a primary prevention population.
      METHODS: Patients presenting for cardiovascular preventive care (n = 356) who
      underwent echocardiography as well as carotid artery ultrasound and/or coronary
      calcium scoring were included. RESULTS: EAT thickness was weakly correlated with
      Framingham risk score. The prevalence of carotid plaque was significantly greater
      in those with EAT thickness >= 5.0 mm who either had low Framingham risk scores
      or had body mass indexes >= 25 kg/m(2), compared with those with EAT thickness
      <5.0 mm. No significant association between EAT thickness and carotid intima
      media thickness or coronary calcium score existed. CONCLUSION: EAT thickness >=
      5.0 mm may identify an individual with a higher likelihood of having detectable
      carotid atherosclerosis.

PMID- 21185149
TI  - The use of atomic force microscopy to study the pathologic effects of anti
      annexin autoantibodies.
AB  - Patients with recurrent pregnancy loss and a history of thrombotic events have
      often been noted to have autoantibodies directed at annexin A5. However, the
      relationship of these autoantibodies to immunopathology is still unknown,
      although it has been proposed that they have a direct effect on the function of
      annexin A5. Annexin A5 may be a significant immunological target with pathologic
      implications. Essentially, annexin A5 is an anticoagulant protein that
      crystallizes over negatively charged phospholipid surfaces and thereby blocks
      them from availability for coagulation reactions. To address this issue, we have
      taken advantage of our expertise with atomic force microscopy and studied anti
      annexin A5 autoantibodies isolated from patients and focused on the ability of
      these antibodies to influence annexin A5 crystallization on planar mica-supported
      phospholipid bilayers. We report herein that such antibodies from patients, but
      not controls, produced a significant disruption of incomplete annexin A5
      crystalline shield on phospholipid bilayer. In addition, the IgG fraction
      isolated from such patients significantly decreased the velocity of annexin A5
      crystallization. Atomic force microscopy is a powerful tool to study the
      pathologic mechanisms of autoantibodies and the data herein reflect the potential
      of anti-annexin A5 antibodies that produce pathology in a number of varied but
      overlapping clinical conditions, including autoimmune thrombosis and
      antiphospholipid syndrome.

PMID- 21185150
TI  - Transmucosal fixation of the fractured edentulous mandible.
AB  - Transmucosal fixation is a new strategy for the treatment of edentulous
      mandibular fractures using external fixation principles within the oral cavity.
      The component parts of this technique are not new. External fixation, locking
      plates and transmucosal implants represent the foundations of this technique; the
      authors' development has been to bring these established methods together as a
      transmucosal intra oral locking plate fixation technique. The first eight
      patients treated with this technique have achieved bony union, they have no long
      term sensory deficit and all patients were able to eat a soft diet with minimal
      discomfort the day after surgery. The first five of eight patients on long-term
      review showed bony union confirmed radiographically. For the remainder and
      subsequent patients, radiographs have not been scheduled at review, in the
      absence of symptoms.

PMID- 21185151
TI  - A long-term comparative study of two rigid internal fixation techniques in terms
      of masticatory function and neurosensory disturbance after mandibular correction
      by bilateral sagittal split ramus osteotomy.
AB  - Bilateral sagittal split ramus osteotomy (BSSO) is widely used to treat
      mandibular prognathism. Several methods have been described for fixation of the
      bony segments. This study compared two methods of rigid fixation (bicortical
      screws and monocortical miniplates) to identify differences in postoperative
      masticatory function and neurosensory disturbance after 5 years of mandibular set
      back correction. 77 women who had undergone BSSO for Class III malocclusion were
      reviewed, and masticatory functions and neurosensory recovery were examined with
      the appropriate indicators pre- and postoperatively (at approximately 1 month,
      and 1, 2, 3, 4, and 5 years). Masticatory function exhibited similar recovery
      patterns in both groups. Orthognathic surgery improved occlusal force and
      occlusal contact area, but longer than 4 years after surgery may be required for
      postoperative occlusal functions in prognathic patients to reach the level of
      healthy subjects. The groups showed no significant differences in the recovery of
      parameters of masticatory functions and neurosensory disturbance even 5 years
      after surgery. In the evaluation of temporomandibular joint function using the
      Helkimo index, the score was significantly higher for the screw group than for
      the miniplate group. This suggests that BSSO fixed with miniplates may offer a
      relatively safe and reliable procedure yielding adequate results and high patient
      satisfaction.

PMID- 21185152
TI  - A rare cause of a parotid mass: spontaneous pseudoaneurysm of the superficial
      temporal artery.

PMID- 21185153
TI  - Effects of mineralocorticoid receptor antagonist spironolactone on atrial
      conduction and remodeling in patients with heart failure.
AB  - BACKGROUND: Spironolactone was shown to reduce mortality in patients with heart
      failure (HF). However, the effect of spironolactone on the incidence of atrial
      fibrillation remains unknown. Therefore, we examined the effects of
      spironolactone on atrial conduction and remodeling in patients with HF. METHODS
      AND RESULTS: A total of 21 patients with HF were divided into either
      spironolactone group (n=11) or control group (n=10). The patients were followed
      up for 12 months. Blood examination, echocardiogram, and signal-averaged
      electrocardiogram were performed at study enrollment and after 3 and 12 months of
      treatment. In the spironolactone group, atrial natriuretic peptide tended to
      reduce, left atrium dimension was significantly smaller, the ratio of E wave to A
      wave tended to improve, and P-duration was significantly shortened. CONCLUSIONS:
      Spironolactone improves atrial conduction and remodeling in patients with HF.

PMID- 21185154
TI  - Effect of preoperative hemoglobin A1c levels on long-term outcomes for diabetic
      patients after off-pump coronary artery bypass grafting.
AB  - BACKGROUND: Diabetes mellitus is an independent risk factor for cardiovascular
      events after coronary artery bypass grafting (CABG), and hemoglobin A1c (HbA1c)
      is the most convenient marker for monitoring glycemic control among diabetic
      patients. However, few studies have reported the impact of baseline HbA1c levels
      on outcomes for diabetic patients after CABG. This study therefore aimed to
      investigate whether preoperative HbA1c levels in diabetic patients are predictive
      of long-term outcomes after off-pump CABG (OPCAB). METHODS AND RESULTS: Of 893
      patients undergoing primary isolated OPCAB at Juntendo University Hospital from
      July 2002 to December 2007, subjects comprised 306 diabetic patients <80 years
      old. We divided these patients into 3 groups according to the preoperative HbA1c
      levels. No significant differences in baseline characteristics, angiographic
      findings, or operative parameters were apparent among the 3 groups. No operative
      or in-hospital mortality occurred. All-cause mortality and cardiac mortality
      rates were 6.2% (19 cases) and 1.3% (4 cases), respectively. Kaplan-Meier's
      survival showed no significant differences in all-cause or cardiac mortality (log
      rank test, p=0.26, p=0.17, respectively). Multivariate analysis by Cox's
      proportional hazards model also demonstrated that no covariates predicted
      mortality except for age. CONCLUSIONS: Preoperative HbA1c levels might not
      predict long-term outcomes for diabetic patients undergoing OPCAB. Careful
      evaluation for diabetes should be needed in preoperative management of CABG.

PMID- 21185155
TI  - Clinical Global Impression of Improvement (CGI-I) as a valid proxy measure for
      remission in schizophrenia: analyses of ziprasidone clinical study data.
AB  - OBJECTIVE: To determine the degree to which a proxy measure of remission in
      schizophrenia correlates with the criteria identified by the Remission in
      Schizophrenia Working Group, and how well early treatment response to ziprasidone
      predicts remission. METHODS: Data from 10 ziprasidone studies were analyzed to
      determine rates of remission achieved with ziprasidone using a remission
      definition of Clinical Global Impression of Improvement (CGI-I) of 1, and
      compared with rates of remission achieved using the remission working group
      criteria. Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric
      Rating Scale (BPRS) scores were then investigated as predictors of remission.
      RESULTS: A CGI-I score of 1 correlated with the remission criteria developed by
      the remission working group. In the combined ziprasidone arms, BPRS scores at
      Weeks 1, 3, and 4 successfully predicted PANSS remission (p<0.01) and BPRS
      remission (p<0.0001) at study endpoint (44-196weeks). PANSS scores (at Weeks 1,
      3, and 4) successfully predicted PANSS remission (p<0.01) at study endpoint.
      PANSS scores at Week 3 successfully predicted BPRS remission (p=0.02) at study
      endpoint. A CGI-I score of 1 or 2 at Week 1 also successfully predicted remission
      in schizophrenia. CONCLUSION: The findings show a correlation between clinical
      and research scales (remission working group criteria) for the assessment of
      remission in schizophrenia. This proxy measure for the assessment of remission
      should be easy to apply in a clinical setting and facilitates the prediction of
      remission in schizophrenia.

PMID- 21185156
TI  - The atypical anti-psychotic clozapine decreases bone mass in rats in vivo.
AB  - BACKGROUND: Fracture risk is increased in patients with schizophrenia, who often
      receive long-term therapy with anti-psychotic drugs. The mechanisms by which
      skeletal fragility is increased in patients with psychosis include increased risk
      of falling, but direct skeletal toxicity of anti-psychotic drugs is a possibility
      that has not been investigated. METHODS: We examined the skeletal effects, in
      vivo and in vitro, of a typical anti-psychotic drug, haloperidol, which primarily
      inhibits dopaminergic signaling, and an atypical anti-psychotic drug, clozapine,
      which predominantly inhibits serotonergic signaling. RESULTS: In growing rats, 42
      days of clozapine treatment reduced whole body bone mineral density by 15%
      (P<0.01 vs vehicle), and trabecular and cortical bone volume, as assessed by
      microcomputed tomography, by 29% and 15%, respectively (P<0.05 vs vehicle for
      each). Treatment with haloperidol did not affect bone density. Clozapine, but not
      haloperidol, transiently increased levels of serum corticosterone, and decreased
      levels of serum testosterone. In vitro, clozapine dose-dependently decreased
      osteoblast mitogenesis, osteoblast differentiation and osteoclastogenesis, while
      haloperidol did not affect any of these parameters. CONCLUSIONS: These data
      demonstrate that clozapine, but not haloperidol, exerts adverse skeletal effects
      in rodents, and that this effect may be attributable to direct actions to reduce
      osteoblast growth and function. Long-term administration of clozapine may
      therefore negatively affect bone health, and clinical studies to investigate this
      possibility are warranted.

PMID- 21185157
TI  - Association between HTR2C polymorphisms and metabolic syndrome in patients with
      schizophrenia treated with atypical antipsychotics.
AB  - BACKGROUND: Previous research indicates that common single-nucleotide
      polymorphisms (SNPs) in the serotonin 5-HT2C receptor gene (HTR2C) are associated
      with metabolic syndrome (MetS) related to antipsychotic treatment. This study
      analyzes a large sample of patients with schizophrenia treated with atypical
      antipsychotics to determine whether variation in the HTR2C is associated with
      MetS. METHODS: Six tag SNPs, capturing all common genetic variations in the HTR2C
      gene in the Han population, were genotyped in 456 Chinese schizophrenic
      inpatients treated with atypical antipsychotics (clozapine: 171, olanzapine: 91,
      and risperidone: 194). RESULTS: Single-marker based analysis shows that of the
      six HTR2C SNPs, the rs498177 SNP showed a significant association with MetS in
      female patients, and the C allele was associated with an increased risk of MetS
      (for genotype TT/TC/CC: MetS vs. non-MetS=50%/27%/23% vs. 69%/28%/3%, and for
      allele T/C: MetS vs. non-MetS=63%/37% vs. 83%/17%, p=0.0007). Haplotype analysis
      shows that the A-C type of rs521018-rs498177 in the HTR2C gene significantly
      decreased the risk of MetS (corrected p=0.0108) in female patients. CONCLUSIONS:
      The results of this study support the role of HTR2C genetic variants in
      susceptibility to MetS in patients treated with atypical antipsychotics. However,
      this association is gender-dependent.

PMID- 21185158
TI  - Actin dynamics regulate immediate PAR-2-dependent responses to acute epidermal
      permeability barrier abrogation.
AB  - BACKGROUND: Lamellar body (LB) secretion and terminal differentiation of stratum
      granulosum (SG) cells are signaled by both protease activated receptor-2 (PAR-2)
      and caveolin-1 (cav-1). OBJECTIVE: To address the early dynamics of LB secretion,
      we examined cytoskeletal remodeling of keratinocytes in 3 mouse models following
      acute barrier abrogation: hairless mice, PAR-2 knockout (-/-) and cav-1 -/-.
      METHODS AND RESULTS: Under basal conditions, globular (G)-actin accumulates in SG
      cells cytosol, while filamentous (F)-actin is restricted to peri-membrane
      domains. Barrier abrogation induces the apical movement of F-actin and the
      retreat of the SG-G-actin front, paralleled by upstream cytoskeletal kinases
      activation. This phenomenon was both enhanced by PAR-2 agonist, and inhibited by
      cytochalasin-D and in PAR-2 knockout mice. We found that plasma membrane
      conformational changes causing LB secretion are controlled by PAR-2-dependent
      cytoskeletal rearrangements. We next addressed the interaction dynamics between
      cytoskeleton and plasma membrane following PAR-2-induced actin stress fiber
      formation in both cav-1 -/- and wildtype cells. Actin stress fiber formation is
      increased in cav-1 -/- cells prior to and following PAR-2 agonist peptide
      treatment, while absence of cav-1 inhibits E-cadherin-mediated cell-to-cell
      adhesion. CONCLUSION: PAR-2 drives cytoskeletal/plasma membrane dynamics that
      regulate early LB secretion following barrier abrogation, stress fiber formation
      and keratinocyte adhesion.

PMID- 21185159
TI  - Use of functional interactions with MarA to discover chromosomal genes affecting
      antibiotic susceptibility in Escherichia coli.

PMID- 21185160
TI  - Bactericidal oncocin derivatives with superior serum stabilities.
AB  - The proline-rich antimicrobial peptide oncocin is remarkably active in vitro
      against a number of important Gram-negative bacteria of concern to humans owing
      to their increasing resistance to antibiotics, i.e. Enterobacteriaceae
      (Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae) and non
      fermenting species (Acinetobacter baumannii and Pseudomonas aeruginosa).
      Degradation of oncocin in mouse serum was investigated in this study. Several
      approaches to stabilise the main cleavage sites (C-terminal to Arg-15 and N
      terminal to Arg-19) by substituting either or both arginine (Arg) residues with
      non-proteinogenic amino acids, i.e. alpha-amino-3-guanidino-propionic acid,
      homoarginine, nitro-arginine, N-methyl-arginine, beta-homoarginine, D-arginine (D
      Arg) or ornithine (Orn), were tested. These modifications were found to increase
      the half-life of oncocin in full mouse serum. For oncocin with two Orn residues
      in positions 15 and 19, the half-life in full serum increased from 25 min to 3 h.
      An increase of >8 h was observed for oncocin with two D-Arg residues at these
      same positions. The antibacterial activities of these modified sequences were
      slightly better than the original oncocin sequence. Moreover, the three most
      stable analogues were found to be bactericidal against E. coli and were not toxic
      to HeLa cells or haemolytic to human erythrocytes.

PMID- 21185161
TI  - A facile synthesis and characterization of Ag, Au and Pt nanoparticles using a
      natural hydrocolloid gum kondagogu (Cochlospermum gossypium).
AB  - An environmentally benign method for the synthesis of noble metal nanoparticles
      has been reported using aqueous solution of gum kondagogu (Cochlospermum
      gossypium). Both the synthesis, as well as stabilization of colloidal Ag, Au and
      Pt nanoparticles has been accomplished in an aqueous medium containing gum
      kondagogu. The colloidal suspensions so obtained were found to be highly stable
      for prolonged period, without undergoing any oxidation. SEM-EDXA, UV-vis
      spectroscopy, XRD, FTIR and TEM techniques were used to characterize the Ag, Au
      and Pt nanoparticles. FTIR analysis indicates that -OH groups present in the gum
      matrix were responsible for the reduction of metal cations into nanoparticles. UV
      vis studies showed a distinct surface plasmon resonance at 412 and 525 nm due to
      the formation of Au and Ag nanoparticles, respectively, within the gum network.
      XRD studies indicated that the nanoparticles were crystalline in nature with face
      centered cubic geometry. The noble metal nanoparticles prepared in the present
      study appears to be homogeneous with the particle size ranging between 2 and 10
      nm, as evidenced by TEM analysis. The Ag and Au nanoparticles formed were in the
      average size range of 5.5+/-2.5 nm and 7.8+/-2.3 nm; while Pt nanoparticles were
      in the size range of 2.4+/-0.7 nm, which were considerably smaller than Ag and Au
      nanoparticles. The present approach exemplifies a totally green synthesis using
      the plant derived natural product (gum kondagogu) for the production of noble
      metal nanoparticles and the process can also be extended to the synthesis of
      other metal oxide nanoparticles.

PMID- 21185162
TI  - Protective effect of lactofermented beetroot juice against aberrant crypt foci
      formation and genotoxicity of fecal water in rats.
AB  - The aim of the study was to investigate the effects of beetroot juice fermented
      by Lactobacillus brevis 0944 and Lactobacillus paracasei 0920 (FBJ) on carcinogen
      induction of aberrant crypt foci (ACF) in rat colon. N-Nitroso-N-methylurea (MNU)
      was used as carcinogen, which was administrated intragastrically at a dose of 50
      mg/kg on the 23rd and 26th day of the experiment. Additionally, we investigated
      the cytotoxicity and genotoxicity of fecal water from experimental animals in the
      Caco 2 cell line, evaluated by MTT/NRU tests and the comet assay, respectively,
      as well as by the count of bacteria adhered to colon epithelium assessed by
      fluorescence in situ hybridization and DAPI staining. The experimental rats were
      divided into four groups based on diet type: basal diet, basal diet supplemented
      with FBJ, basal diet and MNU treatment, and basal diet supplemented with FBJ and
      MNU treatment. FBJ significantly reduced the number of ACF in MNU-treated rats
      (from 55+/-18 to 21+/-6). Moreover, the number of extensive aberrations (more
      than 4 crypts in a focus) decreased from 45+/-21 to 7+/-4. Fecal water obtained
      from rats fed with an MNU-containing diet induced pronounced cytotoxic and
      genotoxic effects in Caco 2 cells, but FBJ supplementation of the diet abolished
      these effects. The presence of FBJ in the diet significantly increased the count
      of bacteria, including Lactobacillus/Enterococcus, adhered to colonic epithelium.
      In conclusion, supplementation of the diet with lactofermented beetroot juice may
      provide protection against precancerous aberrant crypt formation and reduce the
      cytotoxic and genotoxic effects of fecal water.

PMID- 21185164
TI  - Effect of viral upper respiratory tract infection on the urge-to-cough sensation.
AB  - BACKGROUND: Recently, interest has emerged in the sensation of irritation that
      precedes the motor act of coughing; this phenomenon has been termed the urge-to
      cough (UTC). Although one previous study has demonstrated a transient enhancement
      of cough reflex sensitivity during acute upper respiratory tract infection (URI),
      the effect of URI on UTC has not previously been investigated. METHODS: Employing
      standard cough challenge methodology, we measured cough reflex sensitivity in 24
      otherwise healthy adult nonsmokers during URI and again after recovery (4-8 weeks
      later) by determining C(2) and C(5), the concentrations of capsaicin inducing 2
      or more and 5 or more coughs, respectively. In addition, we determined the
      capsaicin concentration at which the UTC sensation first occurred, without an
      associated motor cough, and termed it C(u). Furthermore, we determined the
      difference between concentrations of capsaicin inducing the first motor event of
      cough (C(1)) and C(u), and have termed it C(Delta). RESULTS: During URI, cough
      reflex sensitivity as measured by C(1) (p = 0.033) and C(5) (p = 0.001), as well
      as the urge-to-cough threshold, C(u) (p = 0.046), were significantly enhanced
      compared to the post-recovery state. The degree of change in cough reflex
      sensitivity (C(5)) was significantly greater than that of the urge-to-cough
      threshold, C(u) (p = 0.044). CONCLUSION: Our results demonstrate that the UTC
      sensation is transiently enhanced during URI. We also confirm the results of the
      lone previous study that demonstrated transient enhancement of cough reflex
      sensitivity during URI. The UTC threshold may represent an additional relevant
      end point to measure in future studies evaluating potential antitussive agents.

PMID- 21185163
TI  - The clue of Interstitial Cell of Cajalopathy (ICCpathy) in human diabetic
      gastropathy: the ultrastructural and electrical clues of ICCpathy in human
      diabetic gastropathy.
AB  - Recent studies of diabetic animal models suggest an important role of ICC in the
      pathogenesis of gastropathy. The aim of this study was to characterize the
      ultrastructural features of ICC and record the electrical properties in the
      stomach of patients with type 2 DM. Gastric specimens were obtained from 13
      diabetic patients and 6 control subjects with gastric cancer that underwent
      gastrectomy. All specimens were taken from disease-free areas. The samples were
      processed for both electron microscopic and electrophysiologic examination. The
      characteristic ultrastructural changes of the ICC were observed in both the
      nucleus and cytoplasm in patients with type 2 DM. Wrinkling of the nuclear
      envelope and changes in the cytoplasm such as dilatation of the endoplasmic
      reticulum, an increase of autophagic vacuoles, were more frequently observed in
      the diabetic patients. Apoptosis characterized by nuclear karyorrhexis or
      pyknosis was observed only in the diabetic patients. Slow waves were recorded in
      the circular muscle of stomach. In diabetic patients, the mean resting membrane
      potential was higher and amplitude was lower than controls. These changes of
      electrical activities of slow waves were accompanied with ultrastructural changes
      of ICC, particularly the characteristic nuclear changes. In human diabetic
      patients, the characteristic ultrastructural changes of ICC such as preapoptosis,
      accompanied with electrical dysrhythmia of slow waves, were observed. These
      results show several evidence converging to support that degeneration of the ICC
      may be associated with the pathogenesis of diabetic gastropathy.

PMID- 21185165
TI  - Exogenous lipoid pneumonia. Clinical and radiological manifestations.
AB  - Lipoid pneumonia results from the pulmonary accumulation of endogenous or
      exogenous lipids. Host tissue reactions to the inhaled substances differ
      according to their chemical characteristics. Symptoms can vary significantly
      among individuals, ranging from asymptomatic to severe, life-threatening disease.
      Acute, sometimes fatal, cases can occur, but the disease is usually indolent.
      Possible complications include superinfection by nontuberculous mycobacteria,
      pulmonary fibrosis, respiratory insufficiency, cor pulmonale, and hypercalcemia.
      The radiological findings are nonspecific, and the disease presents with variable
      patterns and distribution. For this reason, lipoid pneumonia may mimic many other
      diseases. The diagnosis of exogenous lipoid pneumonia is based on a history of
      exposure to oil, characteristic radiological findings, and the presence of lipid
      laden macrophages on sputum or BAL analysis. High-resolution computed tomography
      (HRCT) is the best imaging modality for the diagnosis of lipoid pneumonia. The
      most characteristic CT finding in LP is the presence of negative attenuation
      values within areas of consolidation. There are currently no studies in the
      literature that define the best therapeutic option. However, there is a consensus
      that the key measure is identifying and discontinuing exposure to the offending
      agent. Treatment in patients without clinical symptoms remains controversial, but
      in patients with diffuse pulmonary damage, aggressive therapies have been
      reported. They include whole lung lavage, systemic corticosteroids, and
      thoracoscopy with surgical debridement.

PMID- 21185166
TI  - Development of a label-free impedance biosensor for detection of antibody-antigen
      interactions based on a novel conductive linker.
AB  - We developed a label-free impedance biosensor based on an innovative conductive
      linker for detecting antibody-antigen interactions. As the often used
      conventional long chain thiol is a poor conductor, it is not a suitable material
      for use in a faradaic biosensor. In this study, we adopted a thiophene-based
      conductive bio-linker to form a self-assembled monolayer and to immobilize the
      bio-molecules. We used cyclic voltammetry and impedance spectroscopy to verify
      the enhanced conductivity properties. Results showed that the electron transfer
      resistance of this new conductive linker was 3 orders of a magnitude lower than
      for a case using a conventional long chain thiol linker. With the decreased
      impedance (i.e. increased faradaic current), we can obtain a higher signal/noise
      ratio such that the detection limit is improved. Using fluorescence microscopy,
      we verified that our new conductive linker has a protein immobilization
      capability similar to a conventional long chain thiol linker. Also, using S100
      proteins, we verified the protein interaction detection capability of our system.
      Our obtained results showed a linear dynamic range from 10 ng/ml to 10 MUg/ml and
      a detection limit of 10 ng/ml. With our new conductive linker, an electrochemical
      impedance biosensor shows great potential to be used for point-of-care
      applications.

PMID- 21185167
TI  - Nanocrystalline diamond impedimetric aptasensor for the label-free detection of
      human IgE.
AB  - Like antibodies, aptamers are highly valuable as bioreceptor molecules for
      protein biomarkers because of their excellent selectivity, specificity and
      stability. The integration of aptamers with semiconducting materials offers great
      potential for the development of reliable aptasensors. In this paper we present
      an aptamer-based impedimetric biosensor using a nanocrystalline diamond (NCD)
      film as a working electrode for the direct and label-free detection of human
      immunoglobulin E (IgE). Amino (NH(2))-terminated IgE aptamers were covalently
      attached to carboxyl (COOH)-modified NCD surfaces using carbodiimide chemistry.
      Electrochemical impedance spectroscopy (EIS) was applied to measure the changes
      in interfacial electrical properties that arise when the aptamer-functionalized
      diamond surface was exposed to IgE solutions. During incubation, the formation of
      aptamer-IgE complexes caused a significant change in the capacitance of the
      double-layer, in good correspondence with the IgE concentration. The linear
      dynamic range of IgE detection was from 0.03 MUg/mL to 42.8 MUg/mL. The detection
      limit of the aptasensor reached physiologically relevant concentrations (0.03
      MUg/mL). The NCD-based aptasensor was demonstrated to be highly selective even in
      the presence of a large excess of IgG. In addition, the aptasensor provided
      reproducible signals during six regeneration cycles. The impedimetric aptasensor
      was successfully tested on human serum samples, which opens up the potential of
      using EIS for direct and label-free detection of IgE levels in blood serum.

PMID- 21185168
TI  - Foot and ankle fractures at the supination line.
AB  - BACKGROUND: The supination line is a fictive line along the foot and ankle, on
      which over twenty fracture types and approximately ten different ligamentous
      sprain-injuries have been identified. OBJECTIVE: The current study was conducted
      to evaluate the incidence of different types of supination line injuries visible
      at the initial radiographs at the Emergency Department and to determine the type
      and percentage of misdiagnosed injuries. METHOD: Retrospective study of
      consecutive patients who visited the Emergency Department, between January 1 and
      June 30, 2009, after sustaining an injury of the foot or ankle and had a
      radiograph taken within 24 h of the incident. RESULTS: In the 6-month study
      period 1284 patients were included. In these cases the trauma mechanism was a
      sprain in 780 patients (60.7%). Of these patients 310 suffered from a fracture
      (40%). There were 36 (4.6%) false-positive cases and in 91 (11.7%) cases the
      initial diagnosis was false-negative. The number with a missed fracture expressed
      as a percentage of all patients with a fracture was 29.4% (91/310). CONCLUSION:
      Detection of injuries along the supination line remains difficult. This study
      might aid in decreasing the number of misdiagnosed injuries, which is of value as
      these might negatively affect outcome.

PMID- 21185169
TI  - Frontiers in targeting glioma stem cells.
AB  - Patients with glioblastoma multiforme (GBM - WHO grade IV) seldom recover. This
      is due to the infiltrative nature of these tumours and the presence of cellular
      populations with ability to escape therapies and drive tumour recurrence and
      progression. In some cases, these resistant cells exhibit stem properties [glioma
      stem cells (GSC)]. This article aims at discussing relevant issues on GSC
      resistance to current therapies and outlines possible and promising avenues in
      regard to novel therapeutic strategies, such as pharmacological, immunological
      and viral interventions.

PMID- 21185170
TI  - Effects of surface treatment and process parameters on immobilization of
      recombinant yeast cells by adsorption to fibrous matrices.
AB  - The effects of surface properties of Saccharomyces cerevisiae strains 468/pGAC9
      and 468 on adhesion to polyethyleneimine (PEI) and/glutaraldehyde (GA) pre
      treated cotton (CT), polyester (PE), polyester+cotton (PECT), nylon (NL),
      polyurethane foam (PUF), and cellulose re-enforced polyurethane (CPU) fibers were
      investigated. Process parameters (circulation velocity, pH, ionic strength, media
      composition and surfactants) were also examined. 80%, 90%, and 35% of the cells
      were adsorbed onto unmodified CT, PUF, and PE, respectively. PEI-GA pre-treated
      CT and alkali treated PE yielded 25% and 60% cell adhesion, respectively.
      Adsorption rate (K(a)) ranged from 0.06 to 0.17 for CT and 0.06-0.16 for PE at
      varied pH. Adhesion increased by 15% in the presence of ethanol, low pH and ionic
      strength, and decreased by 23% in the presence of yeast extract and glucose.
      Shear flow and 1% Triton X-100 detached 62% and 36% nonviable cells from PE and
      CT, respectively, suggesting that cell immobilization in fibrous-bed bioreactors
      can be controlled to optimize cell density for long-term stability.

PMID- 21185171
TI  - Comparative study of biological hydrogen production by pure strains and consortia
      of facultative and strict anaerobic bacteria.
AB  - In this paper, a simple and rapid method was developed in order to assess in
      comparative tests the production of binary biogas mixtures containing CO(2) and
      another gaseous compound such as hydrogen or methane. This method was validated
      and experimented for the characterisation of the biochemical hydrogen potential
      of different pure strains and mixed cultures of hydrogen-producing bacteria (HPB)
      growing on glucose. The experimental results compared the hydrogen production
      yield of 19 different pure strains and sludges: facultative and strict anaerobic
      HPB strains along with anaerobic digester sludges thermally pre-treated or not.
      Significant yields variations were recorded even between different strains of the
      same species by i.e. about 20% for three Clostridium butyricum strains. The pure
      Clostridium butyricum and pasteurianum strains achieved the highest yields i.e.
      up to 1.36 mol H(2)/mol glucose compared to the yields achieved by the sludges
      and the tested Escherichia and Citrobacter strains.

PMID- 21185172
TI  - Production of 5-hydroxymethylfurfural from glucose catalyzed by hydroxyapatite
      supported chromium chloride.
AB  - Production of 5-hydroxymethylfurfural (HMF) from glucose was studied in ionic
      liquids in the presence of hydroxyapatite supported chromium chloride (Cr-HAP)
      using oil-bath heating and microwave irradiation (MI). Compared with oil-bath
      heating, the MI way obviously increased HMF yield and reduced the reaction time
      from days to several minutes. A maximum HMF yield of 40% was obtained from the
      dehydration of glucose under MI in 2.5 min. This method is potential as an energy
      efficient and cost-effective approach for the conversion of biomass into platform
      chemicals.

PMID- 21185173
TI  - Utilization of PEI-modified Corynebacterium glutamicum biomass for the recovery
      of Pd(II) in hydrochloric solution.
AB  - A new type of biosorbent was developed for binding anionic precious metals
      through cross-linking waste biomass Corynebacterium glutamicum with
      polyethylenimine (PEI). This biomass was evaluated for the removal and recovery
      of palladium and compared to commercial adsorbents, such as Amberjet 4200 Cl,
      Lewatit Monoplus TP 214, SPC-100, and SPS-200. The kinetic experiments revealed
      that the sorption equilibrium was reached with 30 min for the PEI-modified
      biomass. The maximum uptake of the biosorbent was 176.8 mg/g, which was
      calculated using the Langmuir model. The Pd(II) maximum uptake exhibited the
      following order: Amberjet 4200 Cl>Lewatit Monoplus TP 214>PEI-modified
      biomass>SPC-100>SPS-200. Acidified thiourea in 1.0M HCl was used to desorb Pd(II)
      from all of the sorbents examined.

PMID- 21185174
TI  - A kinetic evaluation of anaerobic treatment of swine wastewater at two
      temperatures in a temperate climate zone.
AB  - A static granular bed reactor (SGBR) was used to treat swine wastewater at 24 and
      16 degrees C. At 24 degrees C, the organic loading rate (OLR) was 0.7-5.4 kg
      COD/m(3)day and the average chemical oxygen demand (COD) removal efficiency was
      88.5%, respectively. Meanwhile, at 16 degrees C, the OLR was 1.6-4.0 kg
      COD/m(3)day and the average COD removal efficiency was 68.0%, respectively. The
      SGBR acted as a bioreactor as well as a biofilter. After backwashing, the
      recovery of COD removal was not a function of an OLR but recovery time, while
      that of TSS removal was not a function of either recovery time or the OLR. The
      maximum substrate utilization rate (k(max)) ratio was 1.89 between 24 and 16
      degrees C, and the half velocity constant (K(s)) ratio was 1.22, and the maximum
      specific growth rate (MU(max)) ratio was 4.71. In addition, the temperature
      activity coefficient in this study was determined to be 1.09.

PMID- 21185175
TI  - Earthworm effects on gaseous emissions during vermifiltration of pig fresh
      slurry.
AB  - Treatment of liquid manure can result in the production of ammonia, nitrous oxide
      and methane. Earthworms mix and transform nitrogen and carbon without consuming
      additional energy. The objective of this paper is to analyse whether earthworms
      modify the emissions of NH(3), N(2)O, CH(4) and CO(2) during vermifiltration of
      pig slurry. The experiment used mesocosms of around 50 L, made from a vermifilter
      treating the diluted manure of a swine house. Three levels of slurry were added
      to the mesocosms, with or without earthworms, during one month, in triplicate.
      Earthworm abundance and gas emissions were measured three and five times,
      respectively. There was a decrease in emissions of ammonia and nitrous oxide and
      a sink of methane in treatments with earthworms. We suggest that earthworm
      abundance can be used as a bioindicator of low energy input, and low greenhouse
      gas and ammonia output in systems using fresh slurry with water recycling.

PMID- 21185176
TI  - Performance evaluation and phylogenetic characterization of anaerobic fluidized
      bed reactors using ground tire and pet as support materials for biohydrogen
      production.
AB  - This study evaluated two different support materials (ground tire and
      polyethylene terephthalate [PET]) for biohydrogen production in an anaerobic
      fluidized bed reactor (AFBR) treating synthetic wastewater containing glucose
      (4000 mg L(-1)). The AFBR, which contained either ground tire (R1) or PET (R2) as
      support materials, were inoculated with thermally pretreated anaerobic sludge and
      operated at a temperature of 30 degrees C. The AFBR were operated with a range of
      hydraulic retention times (HRT) between 1 and 8h. The reactor R1 operating with a
      HRT of 2h showed better performance than reactor R2, reaching a maximum hydrogen
      yield of 2.25 mol H(2)mol(-1) glucose with 1.3mg of biomass (as the total
      volatile solids) attached to each gram of ground tire. Subsequent 16S rRNA gene
      sequencing and phylogenetic analysis of particle samples revealed that reactor R1
      favored the presence of hydrogen-producing bacteria such as Clostridium,
      Bacillus, and Enterobacter.

PMID- 21185177
TI  - Synthesis and SAR of 4-(pyrazol-3-yl)-pyridines as novel c-jun N-terminal kinase
      inhibitors.
AB  - The design and synthesis of a novel series of c-jun N-terminal kinase (JNK)
      inhibitors is described. The development of the 4-(pyrazol-3-yl)-pyridine series
      was discovered from an earlier pyrimidine series of JNK inhibitors. Through the
      optimization of the scaffold 2, several potent compounds with good in vivo
      profiles were discovered.

PMID- 21185178
TI  - 6-Benzylamino 4-oxo-1,4-dihydro-1,8-naphthyridines and 4-oxo-1,4
      dihydroquinolines as HIV integrase inhibitors.
AB  - SAR studies on the quinolone carboxylic acid class of HIV-1 integrase inhibitors
      focused on improving the metabolic stability and led to the discovery of 27 and
      38.

PMID- 21185179
TI  - Modulation of i-motif thermodynamic stability by the introduction of UNA
      (unlocked nucleic acid) monomers.
AB  - The influence of acyclic RNA derivatives, UNA (unlocked nucleic acid) monomers,
      on i-DNA thermodynamic stability has been investigated. The 22nt human telomeric
      fragment was chosen as the model sequence for stability studies. UNA monomers
      modulate i-motif stability in a position-depending manner. The largest
      destabilization is observed for position C14, while UNA placed in position A12
      causes significant increase of i-DNA thermodynamic stability. CD curves of UNA
      modified variants imply no structural changes relative to the native i-motif.

PMID- 21185180
TI  - Design, synthesis and antibacterial activity of 3-methylenepyrrolidine formyl
      hydroxyamino derivatives as novel peptide deformylase inhibitors.
AB  - The synthesis and antibacterial activity of 3-methylenepyrrolidine formyl
      hydroxyamino derivatives are reported. The antibacterial activities of these
      derivatives were evaluated to discover SAR at P(1') and P(3') positions, and most
      of these derivatives exhibit better in vitro antibacterial activity than existing
      drugs against drug-resistant clinical isolates including MRSA, PRSP, and
      Haemophilus influenzae.

PMID- 21185181
TI  - Experimental and theoretical investigation of the scope of enantioselective
      ketone allylations employing Nakamura's allylzinc-bisoxazoline reagent.
AB  - The scope of enantioselective allylations employing Nakamura's allylzinc
      bisoxazoline reagent was examined by performing allylations of a selection of
      readily available ketones. Low-to-moderate ee's were observed, and a
      computational study was conducted to rationalize the results. Examination of
      transition structures of previously performed allylations that proceeded with
      high ee revealed the importance of both local and global control elements in
      these successful reactions. The ability of density functional theory methods to
      estimate the enantioselectivity of these asymmetric ketone allylations was
      established. All allylations that were studied computationally exhibited low (<5
      kcal/mol) activation barriers, a result that is consistent with the highly
      reactive nature of Nakamura's reagent.

PMID- 21185182
TI  - Discovery of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered
      azalides active against efflux-mediated resistant Streptococcus pneumoniae.
AB  - A series of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered
      azalides, were discovered, structurally characterized and biologically evaluated.
      They have shown good antibacterial activity against selected Gram-positive and
      Gram-negative bacterial strains. These include N" substituted 9a-(N'-carbamoyl
      gamma-aminopropyl)- (6a,c), 9a-(N'-thiocarbamoyl-gamma-aminopropyl)- (7a,e), 9a
      [N'-(beta-cyanoethyl)-N'-(carbamoyl-gamma-aminopropyl)]- (9a-c, 9g) 9a-[N'-(beta
      cyanoethyl)-N'-(thiocarbamoyl-gamma-aminopropyl)]-derivatives (10d-f) of 5-O
      desosaminyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythronolide A (3). Among the
      synthesized compounds thiourea 7a and urea 9b have shown substantially improved
      activity comparable to azithromycin (1) and significantly better activity than
      the 3-decladinosyl-azithromycin (2) and the parent 3-cladinosyl analogues against
      efflux-mediated resistant S. pneumoniae.

PMID- 21185183
TI  - Design, synthesis, and pharmacological evaluation of azetedine and pyrrolidine
      derivatives as dual norepinephrine reuptake inhibitors and 5-HT(1A) partial
      agonists.
AB  - Compounds with combined norepinephrine reuptake inhibitor (NRI) and serotonin 1A
      (5-HT(1A)) partial agonist pharmacology may offer a new therapeutic approach for
      treating symptoms of neuropsychiatric disorders including ADHD, depression, and
      anxiety. Herein we describe the design and optimization of novel chemical matter
      that exhibits favorable dual NRI and 5-HT(1A) partial agonist activity. Lead
      compounds in this series were found to be devoid of activity at the dopamine
      transporter and were shown to be brain penetrant with high receptor occupancy.

PMID- 21185184
TI  - Molecular probes for the A2A adenosine receptor based on a pyrazolo[4,3
      e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine scaffold.
AB  - Pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine derivatives such as SCH
      442416 display high affinity and selectivity as antagonists for the human A(2A)
      adenosine receptor (AR). We extended ether-linked chain substituents at the p
      position of the phenyl group using optimized O-alkylation. The conjugates
      included an ester, carboxylic acid and amines (for amide condensation), an alkyne
      (for click chemistry), a fluoropropyl group (for (18)F incorporation), and
      fluorophore reporter groups (e.g., BODIPY conjugate 14, K(i) 15 nM). The potent
      and A(2A)AR-selective N-aminoethylacetamide 7 and N-[2-(2-aminoethyl)
      aminoethyl]acetamide 8 congeners were coupled to polyamidoamine (PAMAM) G3.5
      dendrimers, and the multivalent conjugates displayed high A(2A)AR affinity.
      Theoretical docking of an AlexaFluor conjugate to the receptor X-ray structure
      highlighted the key interactions between the heterocyclic core and the binding
      pocket of the A(2A)AR as well as the distal anchoring of the fluorophore. In
      conclusion, we have synthesized a family of high affinity functionalized
      congeners as pharmacological probes for studying the A(2A)AR.

PMID- 21185185
TI  - The discovery of high affinity agonists of GPR109a with reduced serum shift and
      improved ADME properties.
AB  - Amino-anthranilic acid derivatives have been identified as a new class of low
      serum shifted, high affinity full agonists of the human orphan G-protein-coupled
      receptor GPR109a with improved ADME properties.

PMID- 21185187
TI  - The synthesis and biological evaluation of 1-C-alkyl-L-arabinoiminofuranoses, a
      novel class of alpha-glucosidase inhibitors.
AB  - The asymmetric synthesis of 1-C-alkyl-l-arabinoiminofuranoses 1 was achieved by
      asymmetric allylic alkylation (AAA), ring closing metathesis (RCM), and Negishi
      cross coupling as key reactions. Some of the prepared compounds showed potent
      inhibitory activities towards intestinal maltase, with IC(50) values comparable
      to those of commercial drugs such as acarbose, voglibose, and miglitol, which are
      used in the treatment of type 2 diabetes. Among them, the inhibitory activity
      (IC(50)=0.032MUM) towards intestinal sucrase of 1c was quite strong compared to
      the above commercial drugs.

PMID- 21185186
TI  - Molecular recognition and enhancement of aqueous solubility and bioactivity of
      CD437 by beta-cyclodextrin.
AB  - CD437 (6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid) is a
      novel synthetic retinoic acid derivative that has been shown to selectively
      induce apoptosis in human lung cancer cells. This compound, however, is limited
      in its application due to its low solubility in aqueous solutions. One technique
      for increasing the solubility and bioavailability of a cytotoxic agent is the
      formation of inclusion complexes with cyclodextrins. Herein, we report the
      formation and characterization of a 2:1 complex between beta-cyclodextrin (beta
      CD) and CD437. It is shown that CD437 is a tight binder of beta-CD with an
      overall association constant of 2.6+/-0.6*10(7)M(-2). In addition, we demonstrate
      (a) that beta-CD-derived complexation enhances the aqueous solubility of CD437,
      and (b) that a significant increase in the toxicity of CD437 against a human lung
      adenocarcinoma cell line can be achieved by co-treatment with beta-CD.

PMID- 21185188
TI  - THRUMIN1 is a light-regulated actin-bundling protein involved in chloroplast
      motility.
AB  - Chloroplast movement in response to changing light conditions optimizes
      photosynthetic light absorption. This repositioning is stimulated by blue light
      perceived via the phototropin photoreceptors and is transduced to the actin
      cytoskeleton. Some actin-based motility systems use filament reorganizations
      rather than myosin-based translocations. Recent research favors the hypothesis
      that chloroplast movement is driven by actin reorganization at the plasma
      membrane, but no proteins affecting chloroplast movements have been shown to
      associate with both the plasma membrane and actin filaments in vivo. Here we
      identified THRUMIN1 as a critical link between phototropin photoreceptor activity
      at the plasma membrane and actin-dependent chloroplast movements. THRUMIN1
      bundles filamentous actin in vitro, and it localizes to the plasma membrane and
      displays light- and phototropin-dependent localization to microfilaments in vivo.
      These results suggest that phototropin-induced actin bundling via THRUMIN1 is
      important for chloroplast movement. A mammalian homolog of THRUMIN1, GRXCR1, has
      been implicated in auditory responses and hair cell stereocilla development as a
      regulator of actin architecture. Studies of THRUMIN1 will help elucidate the
      function of this family of eukaryotic proteins.

PMID- 21185189
TI  - A role for vasa in regulating mitotic chromosome condensation in Drosophila.
AB  - Vasa (Vas) is a conserved DEAD-box RNA helicase expressed in germline cells that
      localizes to a characteristic perinuclear structure called nuage. Previous
      studies have shown that Vas has diverse functions, with roles in regulating mRNA
      translation, germline differentiation, pole plasm assembly, and piwi-interacting
      RNA (piRNA)-mediated transposon silencing. Although vas has also been implicated
      in the regulation of germline proliferation in Drosophila and mice, little is
      known about whether Vas plays a role during the mitotic cell cycle. Here, we
      report a translation-independent function of vas in regulating mitotic chromosome
      condensation in the Drosophila germline. During mitosis, Vas facilitates robust
      chromosomal localization of the condensin I components Barren (Barr) and CAP-D2.
      Vas specifically associates with Barr and CAP-D2, but not with CAP-D3 (a
      condensin II component). The mitotic function of Vas is mediated by the formation
      of perichromosomal Vas bodies during mitosis, which requires the piRNA pathway
      components aubergine and spindle-E. Our results suggest that Vas functions during
      mitosis and may link the piRNA pathway to mitotic chromosome condensation in
      Drosophila.

PMID- 21185190
TI  - ATP hydrolysis is required for relocating cohesin from sites occupied by its
      Scc2/4 loading complex.
AB  - BACKGROUND: The Cohesin complex that holds sister chromatins together until
      anaphase is comprised of three core subunits: Smc1 and Smc3, two long-rod-shaped
      proteins with an ABC-like ATPase head (nucleotide-binding domain [NBD]) and a
      dimerization domain linked by a 50 nm long intramolecular antiparallel coiled
      coil, and Scc1, an alpha-kleisin subunit interconnecting the NBD domains of Smc1
      and Smc3. Cohesin's stable association with chromosomes is thought to involve
      entrapment of chromatin fibers by its tripartite Smc1-Smc3-Scc1 ring via a poorly
      understood mechanism dependent on a separate Scc2/4 loading complex. A key issue
      concerns where entrapment initially takes place: at sites where cohesin is found
      stably associated or at distinct "loading" sites from which it translocates.
      RESULTS: In this study, we find transition state mutant versions (Smc1E1158Q and
      SmcE1155Q) defective in disengagement of their nucleotide binding domains (NBDs),
      unlike functional cohesin, colocalize with Scc2/4 at core centromeres, sites that
      catalyze wild-type cohesin's recruitment to sequences 20 kb or more away. In
      addition to Scc2/4, the unstable association of transition state complexes with
      core centromeres requires Scc1's association with Smc1 and Smc3 NBDs, ATP-driven
      NBD engagement, cohesin's Scc3 subunit, and its hinge domain. CONCLUSION: We
      propose that cohesin's association with chromosomes is driven by two key events.
      NBD engagement driven by ATP binding produces an unstable association with
      specific loading sites like core centromeres, whereas subsequent ATP hydrolysis
      triggers DNA entrapment, which permits translocation along chromatin fibers.

PMID- 21185192
TI  - Environmental uncertainty and the global biogeography of cooperative breeding in
      birds.
AB  - Understanding why organisms as different as amoebas, ants, and birds cooperate
      remains an important question in evolutionary biology. Although ecology can
      influence cooperation and conflict within animal societies and has been
      implicated in species differences in sociality, the environmental predictors of
      sociality across broad geographic and taxonomic scales remain poorly understood.
      In particular, the importance of temporal variation in selection pressure has
      been underestimated in most evolutionary studies. Environmental uncertainty
      resulting from climatic variation is likely to be an important driver of temporal
      variation in selection pressure and therefore is expected to impact the evolution
      of behavioral, morphological, and physiological traits, including cooperation.
      Using a data set of over 95% of the world's birds, we examine the global
      geography and environmental, biotic, and historical biogeographic predictors of
      avian social behavior. We find dramatic spatial variation in social behavior for
      which environmental and biotic factors--namely, among-year environmental
      variability in precipitation--are important predictors. Although the clear global
      biogeographic structure in avian social behavior carries a strong signal of
      evolutionary history, environmental uncertainty plays an additional key role in
      explaining the incidence and distribution of avian cooperative breeding behavior.

PMID- 21185191
TI  - Zebrafish neural tube morphogenesis requires Scribble-dependent oriented cell
      divisions.
AB  - How control of subcellular events in single cells determines morphogenesis on the
      scale of the tissue is largely unresolved. The stereotyped cross-midline mitoses
      of progenitors in the zebrafish neural keel provide a unique experimental
      paradigm for defining the role and control of single-cell orientation for tissue
      level morphogenesis in vivo. We show here that the coordinated orientation of
      individual progenitor cell division in the neural keel is the cellular
      determinant required for morphogenesis into a neural tube epithelium with a
      single straight lumen. We find that Scribble is required for oriented cell
      division and that its function in this process is independent of canonical
      apicobasal and planar polarity pathways. We identify a role for Scribble in
      controlling clustering of alpha-catenin foci in dividing progenitors. Loss of
      either Scrib or N-cadherin results in abnormally oriented mitoses, reduced cross
      midline cell divisions, and similar neural tube defects. We propose that Scribble
      dependent nascent cell-cell adhesion clusters between neuroepithelial progenitors
      contribute to define orientation of their cell division. Finally, our data
      demonstrate that while oriented mitoses of individual cells determine neural tube
      architecture, the tissue can in turn feed back on its constituent cells to define
      their polarization and cell division orientation to ensure robust tissue
      morphogenesis.

PMID- 21185194
TI  - A journey from benzanilides to dithiobenzanilides: Synthesis of selective
      spasmolytic compounds.
AB  - A series of dithiobenzanilide derivatives was synthesized and each compound was
      evaluated for its ability to reduce KCl-induced contractions of smooth muscle
      preparations of the guinea pig. Starting from a recent publication describing
      benzanilide derivatives as antispasmodic agents, structure-activity guided
      synthesis was performed to obtain compounds with improved spasmolytic activity.
      First, compounds with two amide bonds were designed and second, both amide
      oxygens were replaced by two sp2 sulfur atoms resulting in dithiobenzanilide
      derivatives. The most potent antispasmodic dithiobenzanilide 19 showed improved
      activity with an IC50 value of 0.4 MUM. Moreover, the study also demonstrated
      that these active compounds were able to antagonize the effect of spasmogens like
      acetylcholine and phenylephrine and that the activity is not mediated by
      activation of ATP-dependent potassium channels (K(ATP)-channels) or inhibition of
      endothelial nitric oxide synthase (eNOS).

PMID- 21185195
TI  - Virtual screening and synthesis of quinazolines as novel JAK2 inhibitors.
AB  - JAK2 is an important target in multiple processes associated with tumor growth.
      In this study, virtual screening was employed for hit compound identification
      with chemical libraries using SurflexDock. Subsequently, hit optimization for
      potent and selective candidate JAK2 inhibitors was performed through synthesis of
      diverse C-1 substituted quinazoline derivatives. A novel compound 5p, (6,7
      dimethoxyquinazolin-4-yl)naphthalen-1-ylamine, was thus obtained. JAK2 inhibitory
      activity of 5p was 43% at 20MUM and this was comparable to AG490, a
      representative JAK2 inhibitor. Moreover, 5p showed a positive correlation between
      JAK2 inhibition and cytotoxicity; 5p treatment in HT-29 cells strongly inhibited
      JAK2 activation and subsequent STAT3 phosphorylation, reduced anti-apoptotic
      protein levels, and finally induced apoptosis. This suggests that compound 5p is
      a candidate inhibitor of JAK2 and its downstream STAT3 signaling pathway for
      antitumor therapy. In the docking model, the quinazoline template of 5k, the lead
      compound, occupied a hydrophobic region such as Leu856, Leu855, Ala880, Leu932
      and Gly935, and the highly conserved hydrogen bond was created by 6-OMe of the
      ring template, which binds to the NH of Arg980. Moreover, hydrophobic
      interactions were identified between morpholine moiety and the hydrophobic region
      formed by Leu855, Ala880, Tyr931, Val911 and Met929. Also, compound 5k more
      strongly inhibited JAK2 phosphorylation in mouse embryonic stem cells than AG490.
      Our study shows the successful application of virtual screening for lead
      discovery and we propose that the novel compound 5p can be an effective JAK2
      inhibitor candidate for further antitumor agent research.

PMID- 21185196
TI  - The octadecanoid signaling pathway participates in the chilling-induced
      transcription of omega-3 fatty acid desaturases in Arabidopsis.
AB  - The jasmonate signaling pathway is known to be involved in various stress
      responses in plants, but little is known specifically on the role of the
      octadecanoid pathway in the regulation of omega-3 fatty acid desaturase (FAD)
      genes in response to low temperature. To uncover this problem, the expression
      level of three omega-3 FAD genes (AtFAD3, AtFAD7, and AtFAD8) and the content of
      linolenic acid (C18:3) in both wild type (WT) and mutant (or WT suppressed)
      plants disrupted in the octadecanoid pathway were analyzed under normal
      conditions and the chilling treatment (4  degrees C), respectively. As compared
      with WT plants, chilling-induced organ-specific expressions of omega-3 FAD genes
      significantly changed when the octadecanoid pathway was blocked or suppressed,
      and presented either the "suppressed increase" or the "enhanced decrease"
      tendency. Meanwhile, chilling-induced increases in the content of C18:3 found in
      WT plants, obviously reduced in both leaves and roots, and even turned to a
      decrease in stems when the octadecanoid pathway was disrupted. Overall, the
      transcription of omega-3 FAD genes and the proportion of C18:3 in the whole plant
      both of aos mutants and salicylic acid (SA)-treated plants under chilling stress
      were evidently lower than those of WT plants, except the expression of AtFAD3
      gene in leaves. All these findings indicate that the octadecanoid pathway does
      participate in the chilling-induced transcription of omega-3 FAD genes in
      Arabidopsis.

PMID- 21185197
TI  - Determination of singlet oxygen quenching and protection of biological systems by
      various extracts from seed of Rumex crispus L.
AB  - The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging effect and total
      phenolic contents were evaluated for the screening of singlet oxygen ((1)O(2))
      quenching efficacy of various seed extracts from Rumex crispus L. The butanol and
      ethyl-acetate extracts displayed remarkable effect of DPPH as compared to
      positive control ascorbic acid. The concentrations (QC(50)) of butanol and ethyl
      acetate extracts required to exert 50% reducing effect on (1)O(2) were found to
      be 116 and 82 MUg mL(-1), respectively. Both extracts were also found to protect
      the in vitro biological system from the detrimental effect of (1)O(2) on type II
      photosensitization in Escherichia coli, red blood cell, lactate dehydrogenase and
      histidine. Among all the tested extracts, the ethyl-acetate and butanol extracts
      contained higher amount of total phenolic contents. The results suggest that our
      study may contribute to the development of new bioactive products with potential
      applications to reduce photo-produced oxidative stress involving reactive oxygen
      species in living organisms.

PMID- 21185198
TI  - Larynx preservation: what is the standard treatment?
AB  - Locally advanced laryngeal and hypo-pharyngeal cancers have a rather poor
      prognosis. Up until the early 1990s, standard treatment was total laryngectomy,
      with dramatic functional and social outcome. The introduction of cisplatin based
      chemotherapy made concurrent chemo-radiotherapy (CCRT) the standard treatment for
      selected patients, fit for an organ preservation strategy. Over two decades of
      improvement in nonsurgical management of locally advanced laryngeal cancer is
      reviewed, including the most recent improvements with the introduction of taxanes
      and anti-EGFR targeted therapy.

PMID- 21185199
TI  - Therapeutic effect of a peptide inhibitor of TGF-beta on pulmonary fibrosis.
AB  - Pulmonary fibrosis encompasses several respiratory diseases characterized by
      epithelial cell injury, inflammation and fibrosis. Transforming growth factor
      (TGF)-beta1 is one of the main profibrogenic cytokines involved in the
      pathogenesis of lung fibrosis. It induces fibroblast differentiation into
      myofibroblasts, which produce high levels of collagen and concomitantly loss of
      lung elasticity and reduction of the respiratory function. In the present study,
      we have investigated the effects of P17 (a TGF-beta inhibitor peptide) on IMR-90
      lung fibroblast differentiation in vitro, as well as on the inhibition of the
      development of bleomycin-induced pulmonary fibrosis in mice. It was found that in
      IMR-90 cells, P17 inhibited TGF-beta1-induced expression of connective tissue
      growth factor and alpha-smooth muscle actin. In vivo, treatment of mice with P17
      2days after bleomycin administration decreased lung fibrosis, areas of
      myofibroblast-like cells and lymphocyte infiltrate. P17 also reduced mRNA
      expression of collagen type I, fibronectin and the fibronectin splice isoform EDA
      in the lung, and increased the expression of IFN-gamma mRNA. Finally, therapeutic
      treatment with P17 in mice with already established fibrosis was able to
      significantly attenuate the progression of lung fibrosis. These results suggest
      that P17 may be useful in the treatment of pulmonary fibrosis.

PMID- 21185200
TI  - Mechanism of regulation of autoimmunity by iNKT cells.
AB  - iNKT cells, CD1d dependent natural killer T cells are a unique population of T
      cells. The capacity of iNKT cells to produce regulatory cytokines first provided
      an indication of their regulatory potential. Later on, in experimental models as
      well as in patients afflicted with an auto-immune disease, such as Type 1
      diabetes mellitus, multiple sclerosis, and systemic lupus erythematosus along
      with others, a deficit in iNKT cell number was observed, suggesting the role
      these cells may possibly have in the prevention of auto-immune diseases. More
      importantly, experimental strategies which focused on increasing the volume or
      stimulation of iNKT cells in laboratory animals, demonstrated an improved level
      of protection against the development of auto-immune diseases. This article
      reviews the mechanism of protection against autoimmunity by iNKT cells, discusses
      the obstacles against and indications for the potential use of iNKT cell
      manipulation in the treatment of human auto-immune diseases.

PMID- 21185201
TI  - Assessment of EmboGel--a selectively dissolvable radiopaque hydrogel for embolic
      applications.
AB  - PURPOSE: To evaluate the embolic properties of an alginate-based embolic
      biomaterial (EmboGel) and its solvent (EmboClear) in treatment of aneurysms.
      MATERIALS AND METHODS: EmboGel is a mixture of iohexol and alginate that
      polymerizes into a hydrocoil when delivered through a coaxial catheter with a
      distal mixing tip, exposing alginate to a calcium chloride solution. In contrast
      to previously reported embolic agents, EmboGel can be selectively dissolved by
      EmboClear, a mixture of the enzyme alginate lyase and ethylenediaminetetraacetic
      acid (EDTA). The embolic and contrast properties of EmboGel were assessed in in
      vitro models of saccular aneurysm and an aortic aneurysm endoleak. The
      dissolvability of EmboGel with EmboClear was assessed further after endovascular
      delivery in the New Zealand white rabbit in the native aortoiliofemoral
      territory, a created saccular aneurysm, and the native carotid arteries. RESULTS:
      EmboGel effectively filled aneurysm cavities in the case of stent excluded
      saccular and fusiform aneurysms. EmboGel was readily dissolved by EmboClear in
      vitro and after in vivo embolization. When the distal abdominal aorta and pelvic
      arteries were occluded with EmboGel, within 1 minute of EmboClear infusion,
      patency of the aorta and most of the pelvic circulation was regained as noted by
      angiography. Embolization in the subclavian artery and numerous distal branches
      was rapidly dissolved by EmboClear. Finally, the carotid artery occluded with
      EmboGel regained patency after administration of EmboClear. CONCLUSIONS: EmboGel
      is a dissolvable alginate-based biomaterial that can be used for numerous embolic
      applications. EmboGel can be selectively dissolved with EmboClear, a solution of
      alginate lyase and EDTA.

PMID- 21185202
TI  - Partial recovery after intraarterial pharmacomechanical thrombolysis in
      ophthalmic artery occlusion following nasal autologous fat injection.
AB  - Although autologous fat injection into the face is a widely used procedure in
      aesthetic surgery, heed must be taken because it may cause severe complications
      related to inadvertent arterial embolization, including stroke and vision loss.
      Vision loss may originate from ophthalmic artery occlusion, and no therapeutic
      options have yet been reported for this condition. Herein, the authors report a
      case of ophthalmic artery occlusion following nasal autologous fat injection.
      Partial recovery of choroidal and retinal perfusion, ocular motility, and corneal
      clarity was achieved after intraarterial pharmacomechanical thrombolysis.

PMID- 21185203
TI  - Idiopathic non-specific interstitial pneumonitis responsive to transplant
      associated immunosuppression.

PMID- 21185204
TI  - Twenty-five-year survival after heart-lung transplantation: a milestone.
AB  - Limited information about long-term survivors of heart-lung transplant recipients
      exists. We report a 57-year-old man who has now survived 25 years after a heart
      lung transplant. Initial induction and maintenance immunotherapy was rabbit anti
      thymocyte globulin, cyclosporine, azathioprine, and methylprednisolone. This
      patient is currently alive and working 25 years later and has continued good
      function of the heart-lung graft,without evidence of bronchiolitis obliterans.

PMID- 21185205
TI  - The relationship of ACE and CETP gene polymorphisms with cardiovascular disease
      in a cohort of Asian Indian patients with and those without type 2 diabetes.
AB  - INTRODUCTION: Hypertension and dyslipidemia have been associated with
      cardiovascular disease (CVD). We investigated the association of candidate gene
      polymorphisms in angiotensin-converting enzyme (ACE) and cholesterol ester
      transfer protein (CETP) genes in a cohort of Asian Indian patients with and those
      without type 2 diabetes. METHODS: PCR-based genotyping of insertion/deletion
      (I/D) polymorphism of ACE (rs4646994) and -629C>A of CETP (rs1800775) was carried
      out in 520 individuals, of whom 160 had CVD+type 2 diabetes mellitus (T2DM), 90
      were CVD patients without T2DM, 150 had T2DM with no cardiovascular
      complications, and 120 were age- and sex-matched healthy controls. RESULTS: With
      respect to the ACE gene I/D polymorphism, there was a higher percentage of D/D
      genotype in CVD+T2DM patients, but it was not statistically significant, while
      the CETP -629A allele was significantly associated with CVD+T2DM patients
      (P=.000007; odds ratio=0.46; 95% confidence interval=0.32-0.65) as compared with
      the normal controls and not with CVD alone. Additive interactions between the
      AA+I/I genotypes, AC+I/D genotypes, and AC+D/D were identified between the
      patients and the controls with P values of .0052, .0009, and .0078, respectively.
      CONCLUSIONS: Our study suggests that candidate gene polymorphism -629C>A of CETP
      may serve as a susceptibility biomarker for CVD in T2DM patients. Analyzing the
      combined effect of both ACE and CETP genotypes would enhance the sensitivity and
      specificity of CVD risk estimation in the T2DM patients in our population.

PMID- 21185206
TI  - Age-period-cohort analysis of mortality from epilepsy in Taiwan, 1971-2005.
AB  - BACKGROUND: Age-period-cohort (APC) analysis could provide useful insight into
      the interpretation of time trends for disease rates. This study aimed to
      determine whether the patterns of age, period and cohort effects on epilepsy
      mortality in Taiwan were similar to those in the US and in England and Wales.
      METHODS: We employed a three-phase APC analysis method developed by Keyes and
      Li,(7) which conceptualizes the cohort effect as a partial interaction between
      age and period. The effects of age, period, and cohort were indicated by the
      relative risk (RR) of mortality rates. RESULTS: We found an increase in mortality
      rates in the elderly from 1981-85 to 2001-05 and no decline in mortality rates
      for children, adolescents and adults from 1991-95 to 2001-05. According to APC
      analysis, the RRs increased sharply during adolescence, and leveled off in
      adulthood, and then increased steeply in the elderly. The RR of period effects
      decreased from period 1971-1975 to period 1991-1995 and then increased. With the
      exception of cohort 1911-1915, no significant cohort effects were found.
      CONCLUSION: Despite the limitations of official published mortality data, we
      still found prominent age effects according to APC analysis, which were similar
      to the results of a previous study. However, the patterns of period and cohort
      effects in relation to epilepsy mortality in Taiwan differed from those in
      England and Wales and in the US.

PMID- 21185207
TI  - Diffusion exchange NMR spectroscopy in inhomogeneous magnetic fields.
AB  - Two-dimensional diffusion exchange experiments in the presence of a strong,
      static magnetic field gradient are presented. The experiments are performed in
      the stray field of a single sided NMR sensor with a proton Larmor frequency of
      11.7 MHz. As a consequence of the strong and static magnetic field gradient the
      magnetization has contributions from different coherence pathways. In order to
      select the desired coherence pathways, a suitable phase cycling scheme is
      introduced. The pulse sequence is applied to study diffusion as well as the
      molecular exchange properties of organic solvents embedded in a mesoporous matrix
      consisting of a sieve of zeolites with a pore size of 0.8 nm and grain size of 2
      MUm. This pulse sequence extends the possibilities of the study of transport
      properties in porous media, with satisfying sensitivity in measurement times of a
      few hours, in a new generation of relatively inexpensive low-field NMR mobile
      devices.

PMID- 21185208
TI  - Interdependence of in-cell xenon density and temperature during Rb/129Xe spin
      exchange optical pumping using VHG-narrowed laser diode arrays.
AB  - The (129)Xe nuclear spin polarization (P(Xe)) that can be achieved via spin
      exchange optical pumping (SEOP) is typically limited at high in-cell xenon
      densities ([Xe](cell)), due primarily to corresponding reductions in the alkali
      metal electron spin polarization (e.g. P(Rb)) caused by increased non-spin
      conserving Rb-Xe collisions. While demonstrating the utility of volume
      holographic grating (VHG)-narrowed lasers for Rb/(129)Xe SEOP, we recently
      reported [P. Nikolaou et al., JMR 197 (2009) 249] an anomalous dependence of the
      observed P(Xe) on the in-cell xenon partial pressure (p(Xe)), wherein P(Xe)
      values were abnormally low at decreased p(Xe), peaked at moderate p(Xe) (~300
      torr), and remained surprisingly elevated at relatively high p(Xe) values (>1000
      torr). Using in situ low-field (129)Xe NMR, it is shown that the above effects
      result from an unexpected, inverse relationship between the xenon partial
      pressure and the optimal cell temperature (T(OPT)) for Rb/(129)Xe SEOP. This
      interdependence appears to result directly from changes in the efficiency of one
      or more components of the Rb/(129)Xe SEOP process, and can be exploited to
      achieve improved P(Xe) with relatively high xenon densities measured at high
      field (including averaged P(Xe) values of ~52%, ~31%, ~22%, and ~11% at 50, 300,
      500, and 2000 torr, respectively).

PMID- 21185209
TI  - J-modulation effects in DOSY experiments and their suppression: the Oneshot45
      experiment.
AB  - Diffusion-ordered spectroscopy (DOSY) is a powerful NMR method for identifying
      compounds in mixtures. DOSY experiments are very demanding of spectral quality;
      even small deviations from expected behaviour in NMR signals can cause
      significant distortions in the diffusion domain. This is a particular problem
      when signals overlap, so it is very important to be able to acquire clean data
      with as little overlap as possible. DOSY experiments all suffer to a greater or
      lesser extent from multiplet phase distortions caused by J-modulation, requiring
      a trade-off between such distortions and gradient pulse width. Multiplet
      distortions increase spectral overlap and may cause unexpected and misleading
      apparent diffusion coefficients in DOSY spectra. These effects are described here
      and a simple and effective remedy, the addition of a 45 degrees  purging pulse
      immediately before the onset of acquisition to remove the unwanted anti-phase
      terms, is demonstrated. As well as affording significantly cleaner results, the
      new method allows much longer diffusion-encoding pulses to be used without
      problems from J-modulation, and hence greatly increases the range of molecular
      sizes that can be studied for coupled spin systems. The sensitivity loss is
      negligible and the added phase cycling is modest. The new method is illustrated
      for a widely-used general purpose DOSY pulse sequence, Oneshot.

PMID- 21185210
TI  - Pyrimethamine increases beta-hexosaminidase A activity in patients with Late
      Onset Tay Sachs.
AB  - OBJECTIVE: To assess whether or not pyrimethamine (PMT) can be used to enhance
      beta-hexosaminidase A activity (HexA) in subjects with Late Onset Tay Sachs
      (LOTS), we studied the effect of incremental doses of PMT in vivo in 9 LOTS
      patients carrying the alphaG269S/c.1278insTACT mutations. METHODS: PMT treatment
      was initiated at a dose of 6.25 mg, increasing gradually up to a maximal
      allowable dose of 75 mg daily at 4-6 weeks intervals for a total of up 10 months.
      Mean patients' age was 37.9+/-16.1 yrs (range 20-67 years). RESULTS: Lymphocyte
      HexA activity rose in all subjects, peaking at 78+/-30% over baseline activity
      (mean+/-SD; range 36-114%). The optimal PMT dose varied considerably, averaging
      at 30+/-24.1 mg (range-6.25-75 mg, daily). Further increase in PMT beyond the
      optimal dose was associated with gradual loss of effect on lymphocyte HexA.
      Improvement in speech was seen within several weeks in 4 out of 9 subjects,
      mostly paralleling the initial increment in HexA. Mood stabilization was also
      perceived in 3 subjects, but this was more difficult to assess due to the
      concomitant use of psychotropic/mood stabilizing agents. Reversible decline in
      motor activity manifesting predominantly in more frequent falls was seen in 3
      subjects when the PMT dose was increased beyond the peak effect generating dose.
      CONCLUSIONS: PMT therapy can increase HexA activity in LOTS in vivo. Optimal
      doses should be tailored individually to avoid loss of biochemical effects. Clear
      cut neurological and psychiatric effects are difficult to discern at this time,
      mostly due to short term study follow up and large inter-individual variability.

PMID- 21185212
TI  - Comparison of molecular markers for determining the viability and infectivity of
      Cryptosporidium oocysts and validation of molecular methods against animal
      infectivity assay.
AB  - BACKGROUND: Globally, disinfectants are widely used to intervene in the
      dissemination of Cryptosporidium oocysts. However, extensive investigations of
      oocyst inactivation by various disinfectants are not feasible due to the
      limitations imposed by animal infectivity methods. Molecular techniques provide
      an alternative strategy; however, non-metabolic genes have been used as markers
      for determining viability/infectivity. METHODS: In this study we used
      amyloglucosidase (AG) - a metabolic protein - as a marker to determine
      viability/infectivity of Cryptosporidium. Oocysts were exposed to 6% hydrogen
      peroxide for 2min. Samples were analyzed by cell culture polymerase chain
      reaction (CC-PCR) using PCR primers specific for heat shock protein 70 (hsp70)
      and AG. Both target genes were amplified with the same level of intensity.
      RESULTS: Based on the results it can be concluded that AG is a valid target for
      the study of environmental survival and for the evaluation of the efficacy of
      microbicides against Cryptosporidium using molecular and cellular assays.
      Comparison of the CC-PCR assay and mouse infectivity assay showed a fairly good
      correlation under these test conditions. CONCLUSION: Results indicate that the CC
      PCR assay presents a valid and cost-effective alternative to the mouse
      infectivity assay.

PMID- 21185211
TI  - ARTS and Siah collaborate in a pathway for XIAP degradation.
AB  - ARTS (apoptosis-related protein in the TGF-beta signaling pathway) is a
      mitochondrial protein that binds XIAP (X-linked inhibitor of apoptosis protein)
      upon entering the cytosol, thus promoting cell death. Expression of ARTS is lost
      in some malignancies. Here, we show that ARTS binds to XIAP at BIR1, a domain
      distinct from the caspase-binding sites. Furthermore, ARTS interacts with the E3
      ligase Siah-1 (seven in absentia homolog 1) to induce ubiquitination and
      degradation of XIAP. Cells lacking either Siah or ARTS contain higher steady
      state levels of XIAP. Thus, ARTS serves as an adaptor to bridge Siah-1 to XIAP,
      targeting it for destruction.

PMID- 21185213
TI  - Brain lipid sensing and nervous control of energy balance.
AB  - Nutrient sensitive neurons (glucose and fatty acids (FA)) are present in many
      sites throughout the brain, including the hypothalamus and brainstem, and play a
      key role in the neural control of energy and glucose homeostasis. Through
      neuronal output, FA may modulate feeding behaviour as well as both insulin
      secretion and action. For example, central administration of oleate inhibits food
      intake and glucose production in rats. This suggests that daily variations in
      plasma FA concentrations might be detected by the central nervous system as a
      signal which contributes to the regulation of energy balance. At the cellular
      level, subpopulations of neurons in the ventromedial and arcuate hypothalamic
      nuclei are selectively either inhibited or activated by FA. Possible molecular
      effectors of these FA effects likely include chloride or potassium ion channels.
      While intracellular metabolism and activation of the ATP-sensitive K(+) channel
      appear to be necessary for some of the signaling effects of FA, at least half of
      the FA responses in ventromedial hypothalamic neurons are mediated by interaction
      with FAT/CD36, a FA transporter/receptor that does not require intracellular
      metabolism to activate downstream signaling. Thus, FA or their metabolites can
      modulate neuronal activity as a means of directly monitoring ongoing fuel
      availability by brain nutrient-sensing neurons involved in the regulation of
      energy and glucose homeostasis. Besides these physiological effects, FA overload
      or metabolic dysfunction might impair neural control of energy homeostasis and
      contribute to obesity and/or type 2 diabetes in predisposed subjects.

PMID- 21185214
TI  - Normal plasma FGF23 levels kinetic in tenofovir-related hypophosphatemic
      osteomalacia in an HIV-infected patient with von Recklinghausen disease.
AB  - The antiretroviral agent tenofovir can cause hypophosphatemic osteomalacia due to
      renal phosphate wasting. The potential role for Fibroblast Growth Factor 23
      (FGF23), a phosphaturic hormone is unknown. We evaluated FGF23 plasma
      concentrations in an HIV-positive patient with neurofibromatosis in whom
      hypophosphatemia developed during tenofovir therapy. This patient presented with
      diffuse pain, hypophosphatemia and tubular dysfunction with inadequate phosphate
      reabsorption. The full recovery after tenofovir discontinuation indicates that
      the hypophosphatemia was related to tenofovir and not to von Recklinghausen
      disease. Our data argue against a role for FGF23 in tenofovir-induced
      hypophosphatemia nor in the regulation of hypophosphatemia in this situation.

PMID- 21185215
TI  - A novel and environment-friendly method for preparing dihydropyrano[2,3
      c]pyrazoles in water under ultrasound irradiation.
AB  - A green and convenient approach to the synthesis of dihydropyrano[2,3-c]pyrazoles
      via four-component reaction of aromatic aldehydes, hydrazine, ethyl acetoacetate
      and malononitrile in water under ultrasound irradiation is described. This method
      provides several advantages such as environmental friendliness, shorter reaction
      time, excellent yields, and simple workup procedure.

PMID- 21185216
TI  - Cultural constructions of "obesity": understanding body size, social class and
      gender in Morocco.
AB  - This article presents data from an in-depth qualitative study of overweight and
      diabetic women in Morocco, a North African country experiencing a rapid increase
      in obesity according to national statistics. This case study explores the
      heterogeneous relationship among health, culture and religion in Morocco by
      highlighting the relationship between the intricacies of women's everyday lives
      and their body sizes. My findings suggest that although the Body Mass Index (BMI)
      of adult women has been documented to have increased in Morocco along with other
      macroeconomic changes (i.e., increases in urbanization, etc.), "obesity" has yet
      to be universally medicalized in the Moroccan context. As such women do not
      generally utilize a medicalized concept of obesity in reference to their larger
      body sizes. Rather, cultural constructions of "obesity" are understood through
      cultural understandings of a larger body size, religious beliefs about health and
      illness, and the nature of women's religious participation. This stands in
      contrast to dominant accounts about the region that promote an overall veneration
      of a larger body size for women.

PMID- 21185217
TI  - Inpatient versus outpatient cervical priming for induction of labour: therapeutic
      landscapes and women's preferences.
AB  - A qualitative study was conducted in Australia to explore women's preferences for
      inpatient or outpatient settings for cervical priming for induction of labour.
      The concept of therapeutic landscapes was used to explore the different aspects
      of the home and hospital that make them therapeutic to women. The therapeutic
      value of the home and hospital landscapes was defined by their ability to provide
      women with 'comfort' and 'safety', and women were found to draw on a range of
      contextual factors to negotiate between the comfort of home and the perceived
      safety of the hospital. The study provides important information for health
      professionals to enable them to enhance women's wellbeing should they be offered
      the choice of inpatient or outpatient priming.

PMID- 21185218
TI  - Magnetic resonance imaging assessment of regional abdominal muscle function in
      elite AFL players with and without low back pain.
AB  - Changes in the motor control of trunk muscles have been identified in people with
      low back pain (LBP) including elite football players. Previous research has found
      functional differences in the anatomical regions of abdominal muscles; however,
      this has not been examined in football players with LBP. The aim of this study
      was to investigate if the ability to draw-in the abdominal wall is altered among
      football players with LBP, and to determine if there are functional differences
      between the middle and lower abdominal regions in participants with and without
      LBP. Forty-three elite Australian Football League players were imaged using
      magnetic resonance imaging (MRI) as they drew in their abdominal walls, and the
      trunk cross-sectional area (CSA) was measured in relaxed and contracted states.
      At the lower region, participants with LBP (1.1%) reduced their trunk CSA to a
      lesser extent than those without LBP (3.2%) (P = 0.018). The results also showed
      that the draw-in of the abdominal wall was smaller in Region 1 (8.8%) compared to
      Region 2 (16.0%) and Region 3 (19.7%) (P < 0.001). This study provides evidence
      of regional differences in motor control and altered control of the lower region
      in participants with LBP. This may direct physiotherapists, especially those
      treating athletes, to focus on the lower abdominal region in those with LBP.

PMID- 21185219
TI  - Head eye co-ordination and gaze stability in subjects with persistent whiplash
      associated disorders.
AB  - Symptoms of dizziness, unsteadiness and visual disturbances are frequent
      complaints in persons with persistent whiplash associated disorders. This study
      investigated eye, head co-ordination and gaze stability in subjects with
      persistent whiplash (n = 20) and asymptomatic controls (n = 20). Wireless motion
      sensors and electro-oculography were used to measure: head rotation during
      unconstrained head movement, head rotation during gaze stability and sequential
      head and eye movements. Ten control subjects participated in a repeatability
      study (two occasions one week apart). Between-day repeatability was acceptable
      (ICC > 0.6) for most measures. The whiplash group had significantly less maximal
      eye angle to the left, range of head movement during the gaze stability task and
      decreased velocity of head movement in head eye co-ordination and gaze stability
      tasks compared to the control group (p < 0.01). There were significant
      correlations (r > 0.55) between both unrestrained neck movement and neck pain and
      head movement and velocity in the whiplash group. Deficits in gaze stability and
      head eye co-ordination may be related to disturbed reflex activity associated
      with decreased head range of motion and/or neck pain. Further research is
      required to explore the mechanisms behind these deficits, the nature of changes
      over time and the tests' ability to measure change in response to rehabilitation.

PMID- 21185220
TI  - Computer assisted learning in manipulative therapy education.
AB  - Teaching manipulative therapy is one of the most relevant issues in a
      physiotherapy course. However, for an effective instruction of this topic
      practical experience is considered fundamental. To achieve this purpose, this
      paper presents a computer assisted environment for the practical learning of
      manipulative therapy. The implementation of such a laboratory includes standard
      Personal Computers (PCs), the popular software package Matlab, a digital camera
      and gloves with embedded strength sensors located in the thumb and near the
      wrist. The students wear a glove that measures the applied force in the patient.
      These signals are acquired and stored in a computer providing the teachers with
      the necessary information to analyze the applied force and verify if the manual
      therapy was successful. A digital camera is also used to record the images of the
      student's movements during the manual therapy application. The developed system
      has an autonomy of 15h allowing the application of thirty therapies and the
      corresponding data analysis.

PMID- 21185221
TI  - Rethinking yellow flags.
AB  - The use of Yellow Flags has become widespread in clinical practice, as a means to
      identify clients with low back pain who might not respond favourably to physical
      treatments. However, using questionnaires to identify psychosocial risk factors
      that can result in ongoing pain and suffering is not a straightforward matter,
      and if used without due thought could result in an impoverished service for the
      client. This discussion article aims to raise awareness of the issues that emerge
      when relying on Yellow Flags; including the practicalities of using forced-choice
      questionnaires to identify complex interactions between a client's social
      environment and their psychological state. Yellow Flags are based on a
      biopsychosocial model of health, yet this paper argues that the use of Yellow
      Flags, in practice, belongs within a reductionist paradigm. By calling attention
      to the issues raised, we envisage a better utilization of the biopsychosocial
      model; whereby taking account of a client's unique experience and meaning of pain
      will enable the individual to be managed with a more genuine and insightful
      understanding than seemingly occurs at the present time.

PMID- 21185222
TI  - Upper Limb Neurodynamic Test 1 and symptoms reproduction in carpal tunnel
      syndrome. A validity study.
AB  - The aim of this study was to estimate the validity of the Upper Limb Neurodynamic
      Test 1 (ULNT1) for the diagnosis of Carpal Tunnel Syndrome (CTS) with blind
      comparison to a reference criterion of a compatible clinical presentation and
      abnormal nerve conduction. 47 subjects with suspected CTS were enrolled. All
      patients were tested with nerve conduction studies and ULNT1. Considering results
      as positive in the presence of reproduction of symptoms on affected upper limb,
      or side-to-side differences in elbow extension, or symptoms modified by lateral
      neck side-bending, we estimated sensitivity as 91.67%, specificity as 15%,
      positive likelihood ratio as 1.0784, negative likelihood ratio as 0.5556, and
      post-test probability for negative test as 40%. Using a new criterion, i.e. the
      reproduction of symptoms only in the first three digits of the affected hand, we
      estimated sensitivity as 54.17%, specificity as 70%, positive and negative
      likelihood ratios as 1.8056 and 0.6548, respectively, and post-test probability
      for positive test as 68%. Our investigation suggests that the reproduction of the
      typical current CTS symptoms in the affected hand during ULNT1 testing, improves
      estimation of the probability of the presence of this condition, even if this
      test alone cannot be used to diagnose CTS.

PMID- 21185223
TI  - Effects of taping on thumb alignment and force application during PA
      mobilisations.
AB  - Work related thumb pain (WRTP) is a major problem among manipulative
      physiotherapists. Therapists who maintain the thumb joints in an extended
      alignment during PA mobilisation experience less WRTP. The purposes of this study
      were to investigate what effect taping of the thumbs has on thumb alignment
      during mobilisation and to gain normative data on the mobilisation forces applied
      by student physiotherapists. Forty final year student physiotherapists
      participated and were asked to apply a grade III PA mobilisation onto the C7
      vertebra of one of 32 asymptomatic models. Participants were then instructed to
      apply the same mobilisation onto a force measurement instrument, in both the tape
      and no tape conditions, while the alignment of their metacarpophalangeal (MCP)
      and interphalangeal (IP) joints was noted via video recorder. Thumb alignment
      improved in 72.5% of participants post taping, with significant increases in the
      number of MCP joints maintained in a neutral alignment (p < 0.05). The mean peak
      mobilisation force applied by the students was 70.9 N. Taping of the thumbs prior
      to PA mobilisation improved thumb alignment during mobilisation in this cohort of
      undergraduate students, thus potentially influencing one of the contributory
      factors to WRTP.

PMID- 21185224
TI  - Learning to estimate out-of-plane motion in ultrasound imagery of real tissue.
AB  - In freehand 3D ultrasound (US), the relative positions and orientations of the 2D
      US images are usually obtained from a position tracking device, at the expense of
      clinical convenience. As an alternative or complement to this approach,
      transducer motion can be inferred from image content, using image registration
      techniques to recover in-plane motion and speckle decorrelation to recover out-of
      plane motion. One difficulty with the speckle decorrelation approach is that for
      real tissues, the rate of speckle decorrelation is not only transducer dependent,
      but also medium dependent. This paper proposes a novel method for estimating the
      elevational correlation length of US signals in such media by learning its
      relationship to in-plane image statistics from a pool of synthetic US imagery
      generated from virtual phantoms of varied micro-structure. Learning takes place
      within a sparse Gaussian process regression framework. In experiments with
      synthetic US imagery and real imagery of animal tissue, the approach is shown to
      generalise well across transducer and medium changes, with performance better
      than a method based on speckle classification and comparable to our
      implementation of the heuristic state-of-the-art method. The proposed approach
      better lends itself to improvement through the creation of more realistic
      training sets.

PMID- 21185225
TI  - Pellucid corneal marginal degeneration: A review.
AB  - Pellucid marginal corneal degeneration (PMD) is a rare ectatic disorder which
      typically affects the inferior peripheral cornea in a crescentic fashion. The
      condition is most commonly found in males and usually appears between the 2nd and
      5th decades of life affecting all ethnicities. The prevalence and aetiology of
      this disorder remain unknown. Ocular signs and symptoms of patients with PMD
      differ depending on the severity of the condition. Unless corneal topography is
      evaluated, early forms of PMD may often be undetected however, in the later
      stages PMD can often be misdiagnosed as keratoconus. Visual signs and symptoms
      include longstanding reduced visual acuity or increasing against-the-rule
      irregular astigmatism leading to a slow reduction in visual acuity. In rare
      cases, patients may present with a sudden loss of vision and excruciating ocular
      pain due to corneal hydrops or spontaneous perforation. The vast majority of PMD
      patients are managed using spectacles and contact lenses. Several surgical
      procedures have been used in an attempt to improve visual acuity when spectacles
      and contact lenses do not provide adequate vision correction. Since patients with
      PMD make poor candidates for laser vision correction, an awareness of the
      topographical and slit-lamp features of PMD will be useful to clinicians
      screening for signs of corneal abnormality before corneal refractive surgery.
      This review describes the clinical features of PMD, its differential diagnosis
      and various management strategies presently available.

PMID- 21185226
TI  - Vibrational spectra and natural bond orbital analysis of the herbicidal molecule
      2(4-chlorophenoxy)-2-methyl propionic acid.
AB  - The herbicide 2(4-chlorophenoxy)-2-methyl propionic acid (MCPP) has been
      subjected to NIR FT-Raman and infrared spectral studies. The optimized molecular
      structure, vibrational wavenumbers, IR intensities and Raman activities have been
      calculated by using density functional method (B3LYP) with the standard 6-31G(d)
      basis set. The calculated molecular geometry has been compared with the XRD data.
      The detailed assignments of the normal modes have been performed based on the
      potential energy distribution (PED) following the scaled quantum mechanical force
      field (SQMFF) methodology. The IR and Raman spectra have been plotted for the
      calculated wavenumbers. The simulated spectra satisfactorily coincide with the
      experimental spectra. The strong hyperconjugative interaction and charge
      delocalization that leads to the stability of the molecule have been investigated
      with the aid of natural bond orbital (NBO) analysis.

PMID- 21185227
TI  - Spectroscopic investigations on Naphthol and Tetrahydronaphthol. A theoretical
      approach.
AB  - The computational efficiencies of the semi-empirical method have been compared
      with those of different ab-initio methods for positional isomers of Naphthol and
      Tetrahydro-naphthol type molecules. The efficiencies for computations in case of
      optimized structure, electronic absorption and emission properties are
      investigated. For that semi-empirical approach ZINDO and two different nature of
      ab-initio approaches such as TD-HF/6-311G(d,p) and TD-DFT/B3LYP/6-311G(d,p) were
      considered. The three main approaches are studied here to give the right
      direction of simulation. Semi-empirical AM1/ZINDO function itself can detect the
      trend of molecular transitions and the values obtained by simulations are more
      realistic than ab-initio methods. Ab-initio methods can reproduce exact values of
      first transitional energy with some scaling factor both in ground and in excited
      states of Tetrahydro-naphthol positional isomers whereas no solution or
      prediction could be inferred for Naphthol isomers.

PMID- 21185228
TI  - Effects of cultivation conditions on the uptake of arsenite and arsenic chemical
      species accumulated by Pteris vittata in hydroponics.
AB  - The physiological responses of the arsenic-hyperaccumulator, Pteris vittata, such
      as arsenic uptake and chemical transformation in the fern, have been
      investigated. However, a few questions remain regarding arsenic treatment in
      hydroponics. Incubation conditions such as aeration, arsenic concentration, and
      incubation period might affect those responses of P. vittata in hydroponics.
      Arsenite uptake was low under anaerobic conditions, as previously reported.
      However, in an arsenite uptake experiment, phosphorous (P) starvation-dependent
      uptake of arsenate was observed under aerobic conditions. Time course-dependent
      analysis of arsenite oxidation showed that arsenite was gradually oxidized to
      arsenate during incubation. Arsenite oxidation was not observed in any of the
      control conditions, such as exposure to a nutrient solution or to culture medium
      only, or with the use of dried root; arsenite oxidation was only observed when
      live root was used. This result suggests that sufficient aeration allows the
      rhizosphere system to oxidize arsenite and enables the fern to efficiently take
      up arsenite as arsenate. X-ray absorption near edge structure (XANES) analyses
      showed that long-duration exposure to arsenic using a hydroponic system led to
      the accumulation of arsenate as the dominant species in the root tips, but not in
      the whole roots, partly because up-regulation of arsenate uptake by P starvation
      of the fern was caused and retained by long-time incubation. Analysis of
      concentration-dependent arsenate uptake by P. vittata showed that the uptake
      switched from a high-affinity transport system to a low-affinity system at high
      arsenate concentrations, which partially explains the increased arsenate
      abundance in the whole root.

PMID- 21185229
TI  - Acute response of blood glucose to short-term exercise training in patients with
      type 2 diabetes.
AB  - It is unclear whether the glucose lowering effects of an exercise session are
      augmented by training. Therefore, we sought to assess the effects of a four-week
      exercise training program on the acute response of blood glucose to a single
      exercise session in patients with T2DM. A Quasi experimental design was used.
      Thirty-four patients with T2DM (18 males) completed a four-week exercise regime
      consisting of two 1-h supervised sessions and one 30 min unsupervised home
      session per week. The sessions contained cardiorespiratory and resistance
      exercises. Blood glucose was measured prior to and after each training session.
      Resting heart rate (HR), blood pressure (BP), body composition, lipid profile and
      cardiorespiratory fitness (VO2max) were determined before and after the four week
      training program. Decreases in blood glucose (pre to post exercise session) over
      the four weeks were (mean+/-SD); week 1: 13.3+/-18.6%, week 2: 19.7+/-18.5%, week
      3: 18.1+/-20.8%, week 4: 22.8+/-17.9%. General linear modelling with repeated
      measures ANCOVA showed that there was a significant (p<0.01) time effect over
      this period. Additionally, there were small, but significant decreases in resting
      heart rate (-6.6+/-10.3 bpm, p=0.001), systolic blood pressure (-5.6+/-14.9 mmHg,
      p=0.043) and fat mass (-1.6+/-3.2%, p=0.024) and an increase in VO(2max) (1.6+/
      3.7 ml/kg/min, p=0.025) over the four weeks. Four weeks of exercise training
      augments the exercise-induced decrease in blood glucose that occurs in a single
      exercise session.

PMID- 21185231
TI  - An innovative model of supportive clinical teaching and learning for
      undergraduate nursing students: the cluster model.
AB  - Students look forward to their clinical practicum to learn within the context of
      reality nursing. As educators we need to actively develop models of clinical
      practicum whereby students are supported to engage and learn in the clinical
      learning environment. The aim of this paper is to describe an innovative model of
      supportive clinical teaching and learning for undergraduate nursing students as
      implemented in a large teaching hospital in New South Wales, Australia. The model
      of supportive clinical teaching and learning situates eight students at a time,
      across a shift, on one ward, with an experienced registered nurse from the ward
      specialty, who is employed as the clinical teacher to support nursing students
      during their one to two week block practicum. Results from written evaluation
      statements inform the discussion component of the paper for a model that has
      proved to be successful in this large healthcare facility.

PMID- 21185230
TI  - Antipsychotic drugs and obesity.
AB  - Mechanisms underlying antipsychotic cardiometabolic adverse effects are
      incompletely understood. This hampers the identification of high-risk patients,
      low-risk antipsychotics and preventive/ameliorative treatments. Recent clinical,
      molecular and genetic data suggest that: (i) antipsychotic-naive samples provide
      the greatest power for mechanistic studies; (ii) weight and metabolic effects can
      be discordant, pointing to overlapping and distinct mechanisms; (iii)
      antipsychotics affect satiety and energy homeostasis signaling; (iv) the specific
      peptides mediating these effects are unknown but probably overlap with those
      involved in idiopathic obesity; and (v) single nucleotide polymorphisms in genes
      encoding known neurotransmitter receptors and metabolic proteins are promising
      pharmacogenomic targets for countering adverse affects. However, sophisticated
      molecular studies and genome-wide association studies, ideally in antipsychotic
      naive/first episode samples, are needed to further advance the field.

PMID- 21185232
TI  - An evidence-based oral hygiene education program for nursing staff.
AB  - Increasing evidence shows strong statistical correlations between improved oral
      hygiene and reduction in the incidence, and mortality, from health care
      associated pneumonia among elderly. Therefore, it is important that nursing staff
      are well educated in oral hygiene. The objective was to describe the design of a
      new oral hygiene educational program for nursing staff, where the theoretical
      parts of the education were integrated with evidence about the preventive effect
      of improved oral care on respiratory tract infections and health care-associated
      pneumonia among hospitalized or nursing home resident older people. An
      educational model was translated into three educational steps: hands-on training,
      group discussions, and a theoretical lecture including scientific evidence about
      the preventive effect of oral hygiene on respiratory tract infections, and health
      care-associated pneumonia, among older people. Evidence-based oral hygiene
      education seems to be a feasible way to increase the motivation for daily oral
      care tasks among nursing staff, and thus to improve the oral hygiene status among
      the nursing home resident elderly. Further studies are, however, needed to
      further evaluate the effect of evidence-based oral hygiene educations in
      different health care settings and over longer time periods.

PMID- 21185233
TI  - Learning to work collaboratively: nurses' views of their pre-registration
      interprofessional education and its impact on practice.
AB  - One of the challenges of contemporary health care is the need for health and
      social care professionals to work differently to meet the complex needs of
      patients/clients. However it cannot be assumed that these professionals have been
      prepared with the skills and confidence to collaborate effectively, outside of
      traditional professional boundaries. Interprofessional education (IPE) is well
      established as an effective learning and teaching approach to prepare
      practitioners for collaborative practice at the point of qualification (DOH 2001;
      Hale 2003; Morison et al., 2003; Department of Health 2006; Hammick et al.,
      2007). The phenomenological study reported in this paper sought to follow up a
      group of newly qualified adult nurses at six months post-qualification. These
      nurses had undertaken a pre-registration curriculum in which classroom-based
      interprofessional learning was well embedded and formally assessed within their
      three year programme. Data from eight in depth interviews were analysed and five
      key themes were emerged: common understanding of IPE; teaching and learning;
      understanding of professional roles; stereotypes; influence of the practice
      environment. The outcome of the study suggested IPE should be as practice focused
      as possible to improve its relevance to nursing practice. This study contributed
      to the development of an innovative curriculum which provides the opportunity for
      nurses to integrate IPE theory within their collaborative working practice.

PMID- 21185234
TI  - Early-onset versus late-onset Alzheimer's disease: the case of the missing APOE
      E4 allele.
AB  - Some patients with early-onset Alzheimer's disease (AD) present with a distinct
      phenotype. Typically, the first and most salient characteristic of AD is episodic
      memory impairment. A few patients, however, present with focal cortical, non
      memory symptoms, such as difficulties with language, visuospatial, or executive
      functions. These presentations are associated with specific patterns of atrophy
      and frequently with a young age at onset. Age is not, however, the only
      determinant of phenotype; underlying factors, especially genetic factors, seem
      also to affect phenotype and predispose patients to younger or older age at
      onset. Importantly, patients with atypical early-onset disease seldom carry the
      APOE E4 allele, which is the most important risk factor for lowering the age of
      onset in patients with AD. Additionally, theAPOE E4 genotype seems to predispose
      patients to vulnerability in the medial temporal areas, which leads to memory
      loss. Conversely, patients negative for the APOE E4 allele and with early-onset
      AD are more likely to be predisposed to vulnerability of cerebral networks beyond
      the medial temporal lobes. Other factors are probably involved in determining the
      pattern of atrophy, but these are currently unknown.

PMID- 21185235
TI  - Subtotal hysterectomy and myomectomy - vaginally.
AB  - Vaginal subtotal (or supracervical) hysterectomy and vaginal myomectomy are
      elegant procedures rarely carried out by the average gynaecologist. Both
      techniques, however, are easily learned, and in view of the proven advantages of
      vaginal surgery over abdominal or laparoscopic approaches, they are worthy of a
      wider application. Subtotal hysterectomy may be preferred to excision of the
      entire uterus in certain circumstances, and may be carried out vaginally. Vaginal
      myomectomy allows for a more thorough myomectomy and stronger uterine repair than
      a laparoscopic procedure, as well as avoiding abdominal wounds. It may represent
      the optimal approach where fibroids are favourably sited. We first set out the
      case for subtotal hysterectomy and then describe the development of vaginal
      subtotal hysterectomy and vaginal myomectomy. We discuss the evidence supporting
      their use and indications, and then describe techniques for both vaginal
      procedures.

PMID- 21185236
TI  - Extract of grains of paradise and its active principle 6-paradol trigger
      thermogenesis of brown adipose tissue in rats.
AB  - Grains of paradise (GP) is a species of the ginger family, Zingiberaceae,
      extracts of which have a pungent, peppery taste due to an aromatic ketone, 6
      paradol. The aim of this study was to explore the thermogenic effects of GP
      extracts and of 6-paradol. Efferent discharges from sympathetic nerves entering
      the interscapular brown adipose tissue were recorded. Intragastric injection of a
      GP extract or 6-paradol enhanced the efferent discharges of the sympathetic
      nerves in a dose-dependent manner. The enhanced nerve discharges were sustained
      for as long as 3h. The rats did not become desensitized to the stimulatory
      effects these compounds on sympathetic nerve activity. The tissue temperature of
      brown adipose tissue showed significant increase in rats injected with 6-paradol.
      These results demonstrate that GP extracts and 6-paradol activate thermogenesis
      in brown adipose tissue, and may open up new avenues for the regulation of weight
      loss and weight maintenance.

PMID- 21185237
TI  - Determination of firocoxib in equine plasma using high performance liquid
      chromatography.
AB  - A new method of analysis has been developed and validated for the determination
      of firocoxib, a new nonsteroidal anti-inflammatory drug (NSAID) approved for use
      in horses and dogs to control pain and inflammation associated with
      osteoarthritis. Following a liquid extraction using ethyl acetate:hexane (40:60),
      samples were separated by isocratic reversed-phase HPLC on a Sunfire C(18) column
      and quantified using UV detection at 290 nm. The mobile phase was a mixture of
      water with 0.025% trifluoroacetic acid and acetonitrile, with a flow-rate of 1.1
      ml/min. The procedure produced a linear curve over the concentration range 5-1500
      ng/ml with a lower limit of quantification of 5 ng/ml. Intra- and inter-assay
      variability was less than 7%. The average recovery was 98%. The method is
      suitable for the analysis of clinical samples from pharmacokinetic studies and
      can also be used for small volume sample sizes.

PMID- 21185238
TI  - Limits of detection for the determination of mono- and dicarboxylic acids using
      gas and liquid chromatographic methods coupled with mass spectrometry.
AB  - The chromatographic separation and instrumental limits of detection (LODs) were
      obtained for a broad range of C(1)-C(18) monocarboxylic (MCAs) and C(2)-C(14)
      dicarboxylic acids (DCAs) employing either chemical derivatization followed by
      gas chromatography-mass spectrometry and flame ionization detection (GC-MS/FID)
      or direct analysis with liquid chromatography high resolution MS and tandem MS
      (LC-MS). Suitability, efficiency and stability of reaction products for several
      derivatization agents used for esterification (BF(3)/butanol), and
      trimethysilylation, including trimethylsilyl-N-N-dimethylcarbamate (TMSDMC) and
      N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) were evaluated. The lowest
      limits of detection for the majority of compounds below 10 pg (with the exception
      of acetic acid) were obtained for derivatization with BF(3)/butanol followed by
      GC-MS in the total ion current (TIC) mode. Further improvements were achieved
      when applying either selected ion monitoring (SIM), which decreased the LODs to 1
      4 pg or a combination of SIM and TIC (SITI) (2-5 pg). GC-FID provided LODs
      comparable to those obtained by GC-MS TIC. Both trimethylsilylation (followed by
      GC-MS) and direct LC-MS/MS analysis yielded LODs of 5-40 pg for most of the
      acids. For volatile acids the LODs were higher, e.g., 25 and 590 ng for TMSDMC
      and BSTFA derivatized formic acid, respectively, whereas the LC-MS methods did
      not allow for the analysis of formic acid at all.

PMID- 21185239
TI  - Detection of banned nitrofuran metabolites in animal plasma samples using UHPLC
      MS/MS.
AB  - The use of nitrofurans as veterinary drugs in food-producing animals has been
      banned in the EU since the 1990s. Monitoring programs in the EU are based on the
      detection of protein-bound metabolites after slaughter. An UHPLC-MS/MS method was
      developed and validated for pre slaughter determination of four nitrofuran
      metabolites (AHD, AOZ, SEM, AMOZ) in animal plasma (bovine, ovine, equine and
      porcine). This method is proposed as an alternative method for on-farm
      surveillance. Plasma samples were derivatised with 2-nitrobenzaldehyde and
      subsequently extracted with organic solvent. Extracts were concentrated and then
      analysed by UHPLC-MS/MS. The method was validated according to Commission
      Decision 2002/657/EC. Inter-species recovery for AHD, AOZ, SEM and AMOZ was 72,
      74, 57 and 71%, respectively. Decision limits (CCalpha) were calculated from
      within laboratory reproducibility experiments to be 0.070, 0.059, 0.071 and 0.054
      MUg kg(-1), respectively. In addition, the assay was applied to incurred plasma
      samples taken from pigs treated with furazolidone.

PMID- 21185240
TI  - Direct LC-ES-MS/MS determination of phthalates in physiological saline solutions.
AB  - A method for determining a group of phthalic esters (PAEs) in physiological
      saline solutions has been developed. The PAEs studied were dimethyl phthalate,
      diethyl phthalate, butyl benzyl phthalate and dibutyl phthalate. These groups of
      phthalates were determined by liquid chromatography-electrospray ionization
      tandem mass spectrometry, working in positive ion mode. The compounds were
      separated by liquid chromatography working in gradient mode with acetonitrile
      ultrapure water as a mobile phase. The separation was performed starting with 5%
      of acetonitrile and increasing to 75% in 5 min, followed by isocratic elution for
      8 min. The method was precise (with relative standard deviation (RSD) from 1.0 to
      6.8%) and sensitive, with LODs of 0.05, 0.38, 0.05 and 0.82 MUg L-1 for DMP, DEP,
      BBP and DBP, respectively. The proposed analytical method has been applied to
      determine these compounds in different physiological saline solutions
      commercialized in plastic bottles.

PMID- 21185241
TI  - Hollow fiber-based liquid phase microextraction (HF-LPME) for a highly sensitive
      HPLC determination of sulfonamides and their main metabolites.
AB  - In this paper, three phase-hollow fiber-based liquid phase microextraction (HF
      LPME) combined with a HPLC procedure using diode array (DAD) and fluorescence
      detection (FLD) has been developed for the determination of four widely used
      sulfonamides: sulfadiazine, sulfamerazine, sulfamethazine, sulfamethoxazole and
      their main metabolites, the corresponding N(4)-acetyl derivatives: N(4)-acetyl
      sulfadiazine, N(4)-acetyl-sulfamerazine, N(4)-acetyl-sulfamethazine, N(4)-acetyl
      sulfamethoxazole. A Q3/2 Accurel KM polypropylene hollow fiber supporting 1
      octanol was used between a 2 M Na(2)SO(4) aqueous solution (pH 4) as a donor
      phase and aqueous solution (pH 12) as an acceptor phase. The procedure allows
      very low detection and quantitation limits of 0.3-33 ng L(-1) and 0.9-100 ng L(
      1), respectively. The proposed method was applied to the determination of the
      analytes in environmental water samples (surface, tap and wastewater).

PMID- 21185242
TI  - Derivatization strategies for the determination of biogenic amines in wines by
      chromatographic and electrophoretic techniques.
AB  - This paper revises the derivatization approaches for the determination of
      biogenic amines in wines. Since most of these amines display poor spectroscopic
      features to be detected by UV absorption or emission (fluorescence) spectroscopy,
      derivatization is necessary to attain the desired sensitivity. Reagents such as o
      phthaldialdehyde, fluorenylmethylchloroformate, dansyl-Cl and dabsyl-Cl have
      widely been used for analytical labeling through amino group. A comparison of
      features of off- and on-line pre- and post chromatographic/electrophoretic
      labeling is given using 1,2-naphthoquinone-4-sulfonate (NQS) as an example. The
      evaluation of the influence of the wine sample composition on the derivatization
      process indicates that pre-column labeling may undergo more severe matrix
      effects.

PMID- 21185243
TI  - Analysis of the oxido-redox status of plasma proteins. Technology advances for
      clinical applications.
AB  - Reactive oxygen species (ROS) are potentially implicated in renal pathology.
      Direct evidence is available for animal models of glomerulonephritis but the
      demonstration of ROS implication in human diseases is only circumstantial and
      requires further experimental support. One problem limiting any evolution is the
      brief life of ROS (in terms of milliseconds) that makes it difficult their direct
      detection 'in vivo'. An alternative is to look at the products of oxidation of
      proteins that remain in blood as a signature of ROS activity. Recent data have
      shown the presence of oxidation products of albumin (sulfonic (34)Cys albumin) in
      serum of patients with focal-glomerulosclerosis, that is a primary glomerular
      diseases causing nephrotic syndrome. Structural studies based on spectroscopy and
      calorimetry strengthened the relevance of oxidation of the unique free SH groups
      of (34)Cys for conformation of albumin, in analogy with what already reported for
      other proteins. In this review, we present new developments on technologies for
      the detection of the oxido-redox potential of proteins that are based on the
      concept that oxidation is inversely correlated with their free content of
      sulphydryl groups. We describe, in particular, two new iodoacetamide-substituted
      cyanines that have been developed for labelling sulphydryl groups and can be
      utilized as stable dyes prior mono- and bi-dimensional electrophoresis. Proteins
      with low binding with iodoacetamide-cyanines may be considered as surrogate
      biomarkers of ROS activity. Standardization of these techniques and their
      acquisition in more laboratories would enable clinicians to plan screening
      studies on ROS in human diseases.

PMID- 21185244
TI  - [Neonatal sucking blisters: prevalence and differential diagnosis].

PMID- 21185245
TI  - A newborn with unusual morphology: some practical aspects.
AB  - Newborns with an unusual phenotype with or without malformations are common in
      the practice of every paediatrician. Determining whether the phenotype is a
      variation of normal or should be considered abnormal and, if the latter, also
      finding the cause can be extremely difficult. Here the main steps that should be
      followed in the diagnostic procedures are discussed. A careful family history and
      detailed physical examination remain the hallmarks of the investigations in all
      newborns. Very frequently clinical photographs will facilitate discussing
      patients with colleagues. Additional investigations usually include radiological
      examinations of all body parts that show abnormalities, and screening of the
      heart, kidneys, eyes and hearing. The studies with the highest yield are
      cytogenetic analyses which nowadays often involve microarray assays. In the near
      future, total exome sequencing will be available for diagnostic purposes which
      will have a major impact on the diagnostic process.

PMID- 21185246
TI  - Factitious disorder as a differential diagnosis for recurrent skin graft failure.
AB  - This case report presents the history of a 43-year-old man who sustained a
      relatively minor burn to his face but who subsequently suffered significant
      morbidity. Although the wound was grafted on a number of occasions, it failed to
      heal. Multiple investigations were carried out to determine the cause of
      recurrent wound breakdown. It had been suspected that the patient was interfering
      with the wound but this could not be proven initially. He was eventually
      diagnosed with factitious disorder and it was only when this was managed in the
      multi-disciplinary setting that his wound finally healed.

PMID- 21185247
TI  - Scrotal reconstruction by testicular apposition and wrap-around skin grafting.
AB  - Scrotal loss with testicular exposure commonly follows debridement for
      necrotising infections and is devastating to the patient both physically and
      psychologically. This article describes our method of scrotal reconstruction by
      testicular apposition and wrap-around skin grafting. The key elements of our
      technique are: (1) preservation of viable spermatic fascia, (2) suturing the
      testes together with a broad surface area of contact to allow fusion of
      testicular fascial layers into a single scrotal sac and (3) meticulous attention
      to skin graft take. We applied this technique in 27 consecutive patients. Two
      thirds (66%) achieved thin, pliable scrotums that closely mimicked an original
      scrotum while 18% developed well-formed sacs with slight adhesions. This
      technique is simple, reproducible and achieves for the patient an aesthetic
      neoscrotum with minimal morbidity.

PMID- 21185248
TI  - A 24-year-old patient with paraplegia and acquired urethral diverticulum: a case
      report.
AB  - Urethral diverticulum is a rare pathology in male patients. It is most often
      encountered in patients with paraplegia due to iterative catheterizations. The
      diagnosis of a large diverticulum is easy to make when faced with clinical
      symptoms, such as: repeated urinary tract infections, perineal pain and
      especially when there is penile swelling. We report the case of a 24-year-old
      patient with paraplegia and urethral diverticulum. In this case, the issue lies
      in the therapeutic possibilities.

PMID- 21185249
TI  - Cyclin D1 gene polymorphism, A870G, is associated with an increased risk of
      salivary gland tumors in the Chinese population.
AB  - Expression of Cyclin D1 is believed to lead to progression through the G1 to S
      cell cycle checkpoint, and both experimental and pathological evidence suggests
      that overexpression of this protein may increase the risk of several cancers. The
      Cyclin D1 A870G polymorphism may modulate expression of the Cyclin D1 protein and
      is associated with the development of several types of tumor. We investigated the
      association between the Cyclin D1 A870G polymorphism and susceptibility to
      salivary gland tumors (SGTs) by PCR-RFLP in 102 Chinese SGT patients and 101
      healthy controls. The frequencies of the AG (p=0.002; odds ratio (OR), 3.466) and
      AA (p=0.003; OR, 3.133) genotypes of Cyclin D1 were significantly higher in
      patients with SGT than in the healthy controls. The frequencies of these two
      genotypes were also significantly higher in pleomorphic adenoma (PA) patients
      (p=0.002; OR, 2.229), compared with the healthy controls. In addition, the
      expression of Cyclin D1 was found to be significantly higher in PA patients with
      the AA genotype, compared with PA patients with the GG genotype. Taken together,
      our results suggested that the Cyclin D1 A870G polymorphism is associated with an
      increased risk of SGTs in the Chinese population. The Cyclin D1 AA genotype not
      only increased the risk of PA, but also increased the expression of Cyclin D1 in
      this type of tumor.

PMID- 21185250
TI  - Degenerative pleomorphic adenoma of the nasal cavity.
AB  - INTRODUCTION: Malignant salivary gland tumor usually involves the parotid gland.
      Although unusual locations have been reported for such tumors, we here report an
      extremely rare case of nasal location in a salivary gland adenoma with malignant
      transformation. OBSERVATION: A 65-year-old man with diabetes and hypertension
      presented with left nasosinal tumefaction causing nasal obstruction with slow
      evolution and recent onset of epistaxis and slight telecanthus. CT, MRI and
      nasosinal bone biopsy were performed. Treatment was by surgical exeresis on an
      external approach. CONCLUSION: Malignant transformation of a pleomorphic adenoma
      with nasal location is extremely rare and little described in the literature.
      Imaging found strong signs of malignancy, confirmed on histology. Surgical
      exeresis was the only effective treatment option.

PMID- 21185251
TI  - Assessment of mean auditory hazard incurred by occupational exposure to impulse
      noise.
AB  - OBJECTIVES: To assess the collective hearing hazard entailed by occupational
      noise exposure. METHODS: The Late Audio-Sonometric Index (LASI) is a global score
      recommended for following up hearing loss in groups of workers exposed to
      traumatic noise, combining: daily noise exposure level (L(EX,8h) in dB(A));
      individual hearing threshold level at 3 kHz (HTL (3kHz) in dB); HTL(0)(3)(kHz)
      targeted at retirement; and 5 (or 10) years age bracket between 50 and 59 years
      of age. LASI=HTL(0)(3kHz) - HTL (3kHz)+10 log (age - 20) - 10 log (0.23*L(EX,8h) 
      17.36). RESULTS: When L(EX,8h) exceeds 80dB(A) and HTL(0)(3kHz) is at 25dB,
      occasional audiometric surveillance may be recommended for workers exposed to
      hazardous impulse noise: e.g., should the median and the mean LASI values fall
      below 20 for men or 23 for women (indicative threshold values). CONCLUSION: This
      exponential model thus integrates the fact that daily exposure to impulse noise
      may be more harmful for hearing than eight hours exposure to continuous noise of
      equivalent energy.

PMID- 21185252
TI  - A human iPSC model of Hutchinson Gilford Progeria reveals vascular smooth muscle
      and mesenchymal stem cell defects.
AB  - The segmental premature aging disease Hutchinson-Gilford Progeria syndrome (HGPS)
      is caused by a truncated and farnesylated form of Lamin A called progerin. HGPS
      affects mesenchymal lineages, including the skeletal system, dermis, and vascular
      smooth muscle (VSMC). To understand the underlying molecular pathology of HGPS,
      we derived induced pluripotent stem cells (iPSCs) from HGPS dermal fibroblasts.
      The iPSCs were differentiated into neural progenitors, endothelial cells,
      fibroblasts, VSMCs, and mesenchymal stem cells (MSCs). Progerin levels were
      highest in MSCs, VSMCs, and fibroblasts, in that order, with these lineages
      displaying increased DNA damage, nuclear abnormalities, and HGPS-VSMC
      accumulating numerous calponin-staining inclusion bodies. Both HGPS-MSC and -VSMC
      viability was compromised by stress and hypoxia in vitro and in vivo (MSC).
      Because MSCs reside in low oxygen niches in vivo, we propose that, in HGPS, this
      causes additional depletion of the MSC pool responsible for replacing
      differentiated cells lost to progerin toxicity.

PMID- 21185253
TI  - Normal myocardial perfusion on 64-detector resting cardiac CT.
AB  - BACKGROUND: Computed tomography (CT) of the heart is increasingly used to
      characterize not only the coronary arteries but also cardiac structure and
      function. The performance of CT in depicting myocardial perfusion is under active
      investigation. OBJECTIVE: We describe the pattern of normal myocardial perfusion
      on resting 64-detector cardiac CT. METHODS: Patients (n = 33; 20 women, 13 men;
      mean age, 52 years) with normal radionuclide myocardial perfusion imaging and
      normal coronary arteries on CT angiography (120 kVp) comprised the study
      population. Segmental myocardial perfusion on CT was measured in Hounsfield units
      (HU) with manual and semiautomated methods for the 17-segment American Heart
      Association model in both systole and diastole. Segments were aggregated into
      coronary artery territories, from apex to base and by myocardial wall. The
      relationships between myocardial perfusion and various patient factors were
      evaluated. RESULTS: Overall mean myocardial perfusion was 98 HU in systole and 94
      HU in diastole with the manual method (P = .011) and 92 HU in systole and 95 HU
      in diastole with the automated method (P = .001). The septum showed significantly
      higher mean attenuation values than the other walls in systole and diastole with
      both methods. Generally, attenuation values were lower in the left circumflex
      artery territory and in the apex. Bivariate analysis showed higher mean
      myocardial attenuation values for women than men, although this difference did
      not persist on multivariate analysis adjusted for patient size. CONCLUSION:
      Normal mean resting myocardial perfusion correlates with CT attenuation values of
      approximately 92-98 HU on CT angiography in the coronary arterial phase. The
      septum consistently shows greater attenuation values than the other walls.

PMID- 21185254
TI  - Diversity visualization by endonuclease: a rapid assay to monitor diverse
      nucleotide libraries.
AB  - Many experiments require a fast and cost-effective method to monitor nucleic acid
      sequence diversity. Here we describe a method called diversity visualization by
      endonuclease (DiVE) that allows rapid visualization of sequence diversity of
      polymerase chain reaction (PCR) products based on DNA hybridization kinetics
      coupled with the activity of a single-strand specific nuclease. The assay
      involves only a limited number of steps and can be performed in less than 4h,
      including the initial PCR. After PCR, the homoduplex double-stranded DNA (dsDNA)
      is denatured and reannealed under stringent conditions. During the reannealing
      process, incubation with S1 nuclease removes single-stranded loops of formed
      heteroduplexes and the resulting digest is visualized on agarose gel. The
      sequence diversity is inversely proportional to the band intensities of S1
      nuclease surviving dsDNA molecules of expected size. As an example, we employed
      DiVE to monitor the diversity of panning rounds from a single-framework,
      semisynthetic single-chain antibody fragment (scFv) phage display library. The
      results are in good agreement with the observed decrease in diversity in phage
      display panning rounds toward the selection of monoclonal scFv. We conclude that
      the DiVE assay allows rapid and cost-effective monitoring of diversities of
      various nucleotide libraries and proves to be particularly suitable for scaffold
      based randomized libraries.

PMID- 21185255
TI  - Investigating microwave hydrolysis for the traceable quantification of peptide
      standards using gas chromatography-mass spectrometry.
AB  - Over the past decade, a number of endogenous peptides and endogenous peptide
      analogs have been employed in therapeutics and as diagnostic markers. The use of
      peptides as standards for the absolute quantification of proteins has become
      commonly accepted. Consequently, the requirement for standard peptides traceable
      to the International System of Units with low associated measurement uncertainty,
      and for accurate methods of peptide quantification, has increased. Here we
      describe a method of peptide quantification involving microwave-assisted acid
      hydrolysis followed by gas chromatography-mass spectrometry that enables
      traceable quantification of a peptide by exact matching isotope dilution mass
      spectrometry where the total hydrolysis time required is only 3h. A solution of
      angiotensin I was quantified using this method, and the results were in agreement
      with those obtained previously using an oven hydrolysis liquid chromatography
      tandem mass spectrometry method.

PMID- 21185256
TI  - Carbon metabolism and the sign of control coefficients in metabolic adaptations
      underlying K-ras transformation.
AB  - Metabolic adaptations are associated with changes in enzyme activities. These
      adaptations are characterized by patterns of positive and negative changes in
      metabolic fluxes and concentrations of intermediate metabolites. Knowledge of the
      mechanism and parameters governing enzyme kinetics is rarely available. However,
      the signs-increases or decreases-of many of these changes can be predicted using
      the signs of metabolic control coefficients. These signs require the only
      knowledge of the structure of the metabolic network and a limited qualitative
      knowledge of the regulatory dependences, which is widely available for carbon
      metabolism. Here, as a case study, we identified control coefficients with fixed
      signs in order to predict the pattern of changes in key enzyme activities which
      can explain the observed changes in fluxes and concentrations underlying the
      metabolic adaptations in oncogenic K-ras transformation in NIH-3T3 cells. The
      fixed signs of control coefficients indicate that metabolic changes following the
      oncogenic transformation-increased glycolysis and oxidative branch of the pentose
      phosphate pathway, and decreased concentration in sugar-phosphates-could be
      associated with increases in activity for glucose-6-phosphate dehydrogenase,
      pyruvate kinase and lactate dehydrogenase, and decrease for transketolase. These
      predictions were validated experimentally by measuring specific activities. We
      conclude that predictions based on fixed signs of control coefficients are a very
      robust tool for the identification of changes in enzyme activities that can
      explain observed metabolic adaptations in carbon metabolism.

PMID- 21185258
TI  - Normal and abnormal functions of adenosine receptors in the central nervous
      system revealed by genetic knockout studies.
AB  - Endogenous adenosine is a widely distributed upstream regulator of a broad
      spectrum of neurotransmitters, receptors, and signaling pathways that converge to
      contribute to the expression of an array of important brain functions. Over the
      past decade, the generation and characterization of genetic knockout models for
      all four G-protein coupled adenosine receptors, the A1 and A2A receptors in
      particular, has confirmed and extended the neuromodulatory and integrated role of
      adenosine receptors in the control of a broad spectrum of normal and abnormal
      brain functions. After a brief introduction of the available adenosine receptor
      knockout models, this review focuses on findings from the genetic knockout
      approach, placing particular emphasis on the most recent findings. This review is
      organized into two sections to separately address (i) the role of adenosine
      receptors in normal brain processes including neuroplasticity, sleep-wake cycle,
      motor function, cognition, and emotion-related behaviors; and (ii) their role in
      the response to various pathologic insults to brain such as ischemic stroke,
      neurodegeneration, or brain dysfunction/disorders. We largely limit our overview
      to the prominent adenosine receptor subtypes in brain-the A1 and A2A receptors
      for which numerous genetic knockout studies on brain function are available. A1
      and A2A receptor knockouts have provided significant new insights into
      adenosine's control of complex physiologic (e.g., cognition) and pathologic
      (e.g., neuroinflammation) phenomena. These findings extend and strengthen the
      support for A1 and A2A receptors in brain as therapeutic targets in several
      neurologic and psychiatric diseases. However, they also emphasize the importance
      of considering the disease context-dependent effect when developing adenosine
      receptor-based therapeutic strategies.

PMID- 21185260
TI  - Myelin basic protein binds microtubules to a membrane surface and to actin
      filaments in vitro: effect of phosphorylation and deimination.
AB  - Myelin basic protein (MBP) is a multifunctional protein involved in maintaining
      the stability and integrity of the myelin sheath by a variety of interactions
      with membranes and other proteins. It assembles actin filaments and microtubules,
      can bind actin filaments and SH3-domains to a membrane surface, and may be able
      to tether them to the oligodendrocyte membrane and participate in signal
      transduction in oligodendrocytes/myelin. In the present study, we have shown that
      the 18.5 kDa MBP isoform can also bind microtubules to lipid vesicles in vitro.
      Phosphorylation of MBP at Thr94 and Thr97 (bovine sequence) by MAPK, and
      deimination of MBP (using a pseudo-deiminated recombinant form), had little
      detectable effect on its ability to polymerize and bundle microtubules, in
      contrast to the effect of these modifications on MBP-mediated assembly of actin.
      However, these modifications dramatically decreased the ability of MBP to tether
      microtubules to lipid vesicles. MBP and its phosphorylated and pseudo-deiminated
      variants were also able to bind microtubules to actin filaments. These results
      suggest that MBP may be able to tether microtubules to the cytoplasmic surface of
      the oligodendrocyte membrane, and that this binding can be regulated by post
      translational modifications to MBP. We further show that MBP appears to be co
      localized with actin filaments and microtubules in cultured oligodendrocytes, and
      also at the interface between actin filaments at the leading edge of membrane
      processes and microtubules behind them. Thus, MBP may also cross-link
      microtubules to actin filaments in vivo.

PMID- 21185261
TI  - The single pore residue Asp523 in PKD2L1 determines Ca2+ permeation of the
      PKD1L3/PKD2L1 complex.
AB  - The polycystic kidney disease 1-like 3 (PKD1L3)-polycystic kidney disease 2-like
      1 (PKD2L1) complex functions as a Ca(2+)-permeable, non-selective cation channel
      that is activated by acid and its subsequent removal; this is called an off
      response. In this study, we identified a single aspartic residue in PKD2L1 that
      is responsible for the Ca(2+) permeation of the PKD1L3/PKD2L1 complex. Calcium
      imaging analysis using point mutants of negatively charged amino acids present in
      the putative pore regions of PKD1L3 and PKD2L1 revealed that neutralization of
      the aspartic residue in PKD2L1 (D523N), which is conserved among PKD2 family
      members, abolished Ca(2+) permeation, despite robust cell surface expression. In
      contrast, neutralization of the other negatively charged residues of PKD1L3
      (D2049N and E2072Q) and PKD2L1 (D525N and D530N) as well as substitution of
      Asp(523) with a glutamate residue (D523E) had little effect on Ca(2+) permeation
      properties. These results demonstrate that Asp(523) in PKD2L1 is a key
      determinant of Ca(2+) permeation into the PKD1L3/PKD2L1 complex and that PKD2L1
      contributes to forming the pore of the PKD1L3/PKD2L1 channel.

PMID- 21185259
TI  - Recent developments in adenosine receptor ligands and their potential as novel
      drugs.
AB  - Medicinal chemical approaches have been applied to all four of the adenosine
      receptor (AR) subtypes (A(1), A(2A), A(2B), and A(3)) to create selective
      agonists and antagonists for each. The most recent class of selective AR ligands
      to be reported is the class of A(2B)AR agonists. The availability of these
      selective ligands has facilitated research on therapeutic applications of
      modulating the ARs and in some cases has provided clinical candidates. Prodrug
      approaches have been developed which improve the bioavailability of the drugs,
      reduce side-effects, and/or may lead to site-selective effects. The A(2A) agonist
      regadenoson (Lexiscan(r)), a diagnostic drug for myocardial perfusion imaging, is
      the first selective AR agonist to be approved. Other selective agonists and
      antagonists are or were undergoing clinical trials for a broad range of
      indications, including capadenoson and tecadenoson (A(1) agonists) for atrial
      fibrillation, or paroxysmal supraventricular tachycardia, respectively,
      apadenoson and binodenoson (A(2A) agonists) for myocardial perfusion imaging,
      preladenant (A(2A) antagonist) for the treatment of Parkinson's disease, and
      CF101 and CF102 (A(3) agonists) for inflammatory diseases and cancer,
      respectively.

PMID- 21185262
TI  - Design, synthesis and DNA binding properties of orthogonally positioned diamino
      containing polyamide f-IPI.
AB  - An orthogonally positioned diamino/dicationic polyamide f-IPI 2 was synthesized.
      It has enhanced binding affinity, and it showed comparable sequence specificity
      to its monoamino/monocationic counterpart f-IPI 1. Results from CD and DNase I
      footprinting studies confirmed the minor groove binding and selectivity of
      polyamides 1 and 2 for the cognate sequence 5'-ACGCGT-3'. SPR studies provided
      their binding constants: 2.4 * 10(8)M(-1) for diamino 2, which is ~4 times higher
      than 5.4 * 10(7)M(-1) for its monoamino analogue 1.

PMID- 21185263
TI  - The BRAFT1799A mutation confers sensitivity of thyroid cancer cells to the
      BRAFV600E inhibitor PLX4032 (RG7204).
AB  - Aberrant signaling of the Ras-Raf-MEK-ERK (MAP kinase) pathway driven by the
      mutant kinase BRAF(V600E), as a result of the BRAF(T1799A) mutation, plays a
      fundamental role in thyroid tumorigenesis. This study investigated the
      therapeutic potential of a BRAF(V600E)-selective inhibitor, PLX4032 (RG7204), for
      thyroid cancer by examining its effects on the MAP kinase signaling and
      proliferation of 10 thyroid cancer cell lines with wild-type BRAF or BRAF(T1799A)
      mutation. We found that PLX4032 could effectively inhibit the MAP kinase
      signaling, as reflected by the suppression of ERK phosphorylation, in cells
      harboring the BRAF(T1799A) mutation. PLX4032 also showed a potent and BRAF
      mutation-selective inhibition of cell proliferation in a concentration-dependent
      manner. PLX4032 displayed low IC(50) values (0.115-1.156MUM) in BRAF(V600E)
      mutant cells, in contrast with wild-type BRAF cells that showed resistance to the
      inhibitor with high IC(50) values (56.674-1349.788MUM). Interestingly, cells with
      Ras mutations were also sensitive to PLX4032, albeit moderately. Thus, this study
      has confirmed that the BRAF(T1799A) mutation confers cancer cells sensitivity to
      PLX4032 and demonstrated its specific potential as an effective and BRAF(T1799A)
      mutation-selective therapeutic agent for thyroid cancer.

PMID- 21185264
TI  - Inducible disruption of autophagy in the lung causes airway hyper-responsiveness.
AB  - Autophagy is a highly conserved process primarily known for its role in cellular
      adaptation to nutritional stress. This bulk protein degradation pathway relocates
      nutrients during starvation. Recent studies, however, have revealed essential
      roles of autophagy in various organs under normal conditions. Especially,
      autophagy is now recognized as the pathway responsible for the elimination of
      damaged proteins resulting from environmental stress. Lungs are constantly
      exposed to high oxygen tension and environmental chemicals. To investigate the
      importance of autophagy in lung physiology, we used an inducible system to ablate
      Atg7 expression, which is a protein essential for autophagy, in the respiratory
      epithelial cells of adult mice. We found that Atg7 deficiency caused swelling of
      bronchiolar epithelial cells and accumulation of p62, which links substrate
      proteins to the autophagy machinery. Bronchiolar epithelial cells, isolated by
      micro-dissection of lung tissues, had elevated expression of cytoprotective genes
      that are typically activated by Nrf2. Interestingly, Atg7-deficient lungs
      displayed hyper-responsiveness to cholinergic stimuli without apparent
      inflammatory signs. Swollen bronchiolar epithelial cells may have lead to
      mechanical airway constriction and lowered the threshold for the increase of
      airway resistance. This study demonstrates the critical role of autophagy in the
      lungs for the maintenance of pulmonary homeostasis.

PMID- 21185265
TI  - HCN channel activity-dependent modulation of inhibitory synaptic transmission in
      the rat basolateral amygdala.
AB  - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are expressed
      in the central nervous system and play a regulatory role in neuronal
      excitability. In the present study, we examined a physiological role of HCN
      channels in the rat basolateral amygdala (BLA). In vitro electrophysiological
      studies showed that ZD7288 decreased spontaneous inhibitory postsynaptic current
      (sIPSC) without changing miniature IPSC (mIPSC). HCN channel blockade also
      attenuated feedback inhibitions in BLA principal neurons. However, blockade of
      HCN channel had little effects on spontaneous excitatory postsynaptic current
      (sEPSC) and mEPSC. Therefore, HCN channel appeared to decrease BLA excitability
      by increasing the action potential-dependent inhibitory control over the BLA
      principal neurons. Anxiety is reported to be influenced by neuronal excitability
      in the BLA and inhibitory synaptic transmission is thought to play a pivotal role
      in regulating overall excitability of the amygdala. As expected, blockade of HCN
      channels by targeted injection of ZD7288 to the BLA increased anxiety-like
      behavior under elevated plus maze test. Our results suggest that HCN channel
      activity can modulate the GABAergic synaptic transmission in the BLA, which in
      turn control the amygdala-related emotional behaviors such as anxiety.

PMID- 21185266
TI  - Cation-pi and pi-pi stacking interactions allow selective inhibition of
      butyrylcholinesterase by modified quinine and cinchonidine alkaloids.
AB  - Scaffold varied quaternized quinine and cinchonidine alkaloid derivatives were
      evaluated for their selective butyrylcholinesterase (BChE) inhibitory potential.
      K(i) values were between 0.4-260.5MUM (non-competitive inhibition) while
      corresponding K(i)values to acetylcholinesterase (AChE) ranged from 7.0-400MUM
      exhibiting a 250-fold selectivity for BChE. Docking arrangements (GOLD, PLANT)
      revealed that the extended aromatic moieties and the quaternized nitrogen of the
      inhibitors were responsible for specific pi-pi stacking and pi-cation
      interactions with the choline binding site and the peripheral anionic site of
      BChE's active site.

PMID- 21185267
TI  - PTEN deletion prevents ischemic brain injury by activating the mTOR signaling
      pathway.
AB  - It is increasingly clear that the tumor suppressor PTEN (phosphatase and tensin
      homolog deleted on chromosome 10) is a negative regulator of neuronal cell
      survival. However, its molecular mechanisms remain poorly understood. Here we
      found that PTEN/mTOR is critical for controlling neuronal cell death after
      ischemic brain injury. Male rats were subjected to MCAO (middle cerebral artery
      occlusion) followed by pretreating with bpv (pic), a potent inhibitor for PTEN,
      or by intra-cerebroventricular infusion of PTEN siRNA. bpv (pic) significantly
      decreased infarct volume and reduced the number of TUNEL-positive cells. We
      further demonstrated that although bpv (pic) did not affect brain injury-induced
      mTOR protein expression, bpv (pic) prevented decrease in phosphorylation of mTOR,
      and the subsequent decrease in S6. Similarly, down-regulation of PTEN expression
      also reduced the number of TUNEL-positive cells, and increased phospho-mTOR.
      These data suggest that PTEN deletion prevents neuronal cell death resulting from
      ischemic brain injury and that its neuroprotective effects are mediated by
      increasing the injury-induced mTOR phosphorylation.

PMID- 21185268
TI  - Cobalamin deficiency-induced changes of epidermal growth factor (EGF)-receptor
      expression and EGF levels in rat spinal cord.
AB  - We investigated the effect of cobalamin (Cbl) deficiency on epidermal growth
      factor receptor (EGFR) mRNA levels in the spinal cord (SC) and liver of rats made
      Cbl-deficient (Cbl-D) by means of total gastrectomy or a Cbl-D diet, and
      simultaneously measured the levels of the epidermal growth factor (EGF). Both
      methods of inducing Cbl deficiency decreased EGFR expression in the SC and liver.
      Cbl replacement treatment normalized or nearly so most of the abnormalities in
      EGFR expression in the totally gastrectomized (TGX) rats at different times. The
      EGFR-immunostaining intensity decreased in the SC white matter of the Cbl-D rats
      and significantly increased in that of the TGX, Cbl-treated rats. EGF levels
      significantly increased in liver of TGX rats and in SC of 4-month TGX rats, and
      the increases returned to almost normal levels after a postoperative 2-month
      administration of Cbl to TGX rats. These findings demonstrate that Cbl deficiency
      dysregulates the EGFR-EGF dyad in these tissues.

PMID- 21185270
TI  - Anthracyclines and their metabolism in human liver microsomes and the
      participation of the new microsomal carbonyl reductase.
AB  - Anthracyclines (ANTs) are widely used in the treatment of various forms of
      cancer. Although their usage contributes to an improvement in life expectancy, it
      is limited by severe adverse effects-acute and chronic cardiotoxicity. Several
      enzymes from both AKR and SDR superfamilies have been reported as participants in
      the reduction of ANTs. Nevertheless all of these are located in the cytosolic
      compartment. One microsomal reductase has been found to be involved in the
      metabolism of xenobiotics-11beta-HSD1, but no further information has been
      reported about its role in the metabolism of ANTs. The aim of this study is to
      bring new information about the biotransformation of doxorubicin (DOX),
      daunorubicin (DAUN) and idarubicin (IDA), not only in human liver microsomal
      fraction, but also by a novel human liver microsomal carbonyl reductase that has
      been purified by our group. The reduction of ANTs at C-13 position is regarded as
      the main pathway in the biotransformation of ANTs. However, our experiments with
      human liver microsomal fraction show different behaviour, especially when the
      concentration of ANTs in the incubation mixture is increased. Microsomal fraction
      was incubated with doxorubicin, daunorubicin and idarubicin. DOX was both reduced
      into doxorubicinol (DOXOL) and hydrolyzed into aglycone DOX and then subsequently
      reduced. The same behaviour was observed for the metabolism of DAUN and IDA. The
      activity of hydrolases definitely brings a new look to the entire metabolism of
      ANTs in microsomal fraction, as formed aglycones undergo reduction and compete
      for the binding site with the main ANTs. Moreover, as there are two competitive
      reducing reactions present for all three ANTs, kinetic values of direct reduction
      and the reduction of aglycone were calculated. These results were compared to
      previously published data for human liver cytosol. In addition, the participation
      of the newly determined human liver microsomal carbonyl reductase was studied. No
      reduction of DOX into DOXOL was detected. Nevertheless, the involvement in
      reduction of DAUN into DAUNOL as well as IDA into IDAOL was demonstrated. The
      kinetic values obtained were then compared with data which have already been
      reported for cytosolic ANTs reductases.

PMID- 21185269
TI  - In vivo 1H-magnetic resonance spectroscopy study of the attentional networks in
      autism.
AB  - Attentional dysfunction is one of the most consistent findings in individuals
      with autism spectrum disorders (ASD). However, the significance of such findings
      for the pathophysiology of autism is unclear. In this study, we investigated
      cellular neurochemistry with proton magnetic resonance spectroscopy imaging ((1)H
      MRS) in brain regions associated with networks subserving alerting, orienting,
      and executive control of attention in patients with ASD. Concentrations of
      cerebral N-acetyl-aspartate (NAA), creatinine+phosphocreatinine, choline
      containing compounds, myo-inositol (Ins) and glutamate+glutamine (Glx) were
      determined by 3T (1)H-MRS examinations in 14 high-functioning medication-free
      adults with a diagnosis of ASD and 14 age- and IQ-matched healthy controls (HC)
      in the anterior cingulate cortex (ACC), thalamus, temporoparietal junction (TPJ),
      and areas near or along the intraparietal sulcus (IPS). Compared to HC group, the
      ASD group showed significantly lower Glx concentration in right ACC and reduced
      Ins concentration in left TPJ. This study provides evidence of abnormalities in
      neurotransmission related to networks subserving executive control and alerting
      of attention, functions which have been previously implicated in ASD
      pathogenesis.

PMID- 21185271
TI  - MAP kinases in inflammatory bowel disease.
AB  - The mammalian family of mitogen-activated protein kinases (MAPKs) is activated by
      diverse extracellular and intracellular stimuli, and thereby they play an
      essential role in connecting cell-surface receptors to changes in transcriptional
      programs. The MAPK signaling pathways regulate a wide range of cellular
      activities and have been implicated in the pathogenesis of several diseases,
      including inflammatory bowel disease (IBD). This review summarizes recent
      findings on the regulatory mechanism of MAPK signaling pathways, focusing on
      nuclear targets and their role in IBD. Finally, it summarizes how these signaling
      pathways have been exploited for the development of therapeutics and discuss the
      current knowledge of potential MAPK inhibitors and their anti-inflammatory
      effects in clinical trials related to IBD.

PMID- 21185272
TI  - Disease-specific autoantibodies in primary biliary cirrhosis.
AB  - Anti-mitochondrial autoantibodies (AMA) are specific markers of primary biliary
      liver cirrhosis (PBC), a cholestatic autoimmune disease which is characterised by
      a progressive destruction of the biliary epithelial cells followed by fibrosis,
      cirrhosis and liver failure. The prevalence of AMA in PBC is more than 90% and
      they can precede long before the clinical symptoms. AMA are conventionally
      detected by indirect immunofluorescence (IIF) using rodent liver, kidney, and
      stomach sections as substrates. Additionally, different PBC-specific anti-nuclear
      autoantibodies (ANA) can be observed in 30% of patients presenting with multiple
      nuclear dot or nuclear membrane staining patterns, which preferentially are
      identified using HEp-2 cells as substrate. The identification of the major PBC
      specific mitochondrial and nuclear targets has allowed the generation of
      monospecific antigenic targets which are increasingly used in solid-phase assays
      for routine detection of AMA and ANA in mono- or multiparametric screen test
      systems. In the present paper, we give an overview of the diagnostic significance
      of autoantibodies in PBC, discuss the competencies of different techniques used
      for their determination and propose an effective diagnostic strategy.

PMID- 21185273
TI  - Real-time biallelic polymorphism-polymerase chain reaction for chimerism
      monitoring of hematopoietic stem cell transplantation relapsed patients.
AB  - BACKGROUND: An accurate analysis of chimerism kinetics permits early detection of
      hematopoietic stem cell transplantation (HSCT) in patients with high risks of
      graft-versus-host disease or those liable to relapse. Although short tandem
      repeats-PCR (STR-PCR) is the golden standard for quantitative chimerism analysis
      in most of the clinical laboratories, it has a relatively low sensitivity of 5%
      and the detection of low percentage in mixed chimerism is usually delayed. In
      this study, we developed a real-time PCR for chimerism analysis based on the
      informative biallelic polymorphisms (BP). METHODS: The allele frequencies of 19
      selective biallelic polymorphic markers were analyzed using the genomic DNA from
      100 healthy Taiwanese volunteers. The informative biallelic polymorphic markers
      with high discrimination power in the Taiwanese population were identified. The
      TaqMan probe-based real-time BP-PCR for amplification of the informative loci was
      designed and the detection sensitivity was determined. Clinical application of
      real-time BP-PCR in chimerism monitoring was evaluated and was compared with the
      conventional STR-PCR by analyzing the DNA samples obtained at different time
      points post-HSCT from 4 relapsed and 10 non-relapsed patients. RESULTS: Allele
      distribution analysis revealed that the loci of S01a, S03, S04a, S05b, S06, S07b,
      S08b, S09b, S10b and S11a had a relatively high discrimination power and were the
      informative BP for chimerism monitoring in the Taiwanese population. Real-time BP
      PCRs for these 10 BP loci were set up with the detection sensitivity equivalent
      to 0.003-0.006%. Real-time BP-PCR of the 4 HSCT patients revealed the presence of
      recipient-specific DNA at early time point than STR-PCR for 3 of the patients,
      whereas real-time BP-PCR was as effective as STR-PCR in uncovering the sign of
      relapse for one of the patients. In addition, the baseline value for the patients
      with no sign of relapse was 0.127 +/- 0.193% of recipient DNA. CONCLUSION: We
      conclude that real-time BP-PCR is a sensitive and reliable method for chimerism
      monitoring and is superior to the STR-PCR in identifying patients who are at high
      risk for relapse after transplantation.

PMID- 21185274
TI  - Proficiency testing outcomes of 3-hydroxyisovalerylcarnitine measurements by
      tandem mass spectrometry in newborn screening.
AB  - BACKGROUND: The use of tandem mass spectrometry (MS/MS) for the analysis of amino
      acids and acylcarnitines from dried-blood spots (DBS) has become routine practice
      in newborn screening laboratories. The Newborn Screening Quality Assurance
      Program (NSQAP) added 3-hydroxyisovalerylcarnitine (C5OH) into its routine
      quality control and proficiency testing (PT) DBS materials for MS/MS to assure
      the quality of C5OH screening. We report the results from NSQAP evaluations for
      C5OH-enriched DBS, and summarize participant screening practices based on their
      analytical methods. METHODS: NSQAP prepared C5OH-enriched DBS materials for its
      participants. Laboratories reported quantitative and qualitative results. Bias
      plots of quantitative results were constructed using reported data and the
      results were sorted by an analytical method. RESULTS: NSQAP participants reported
      PT specimen 3964 as outside of normal limits for C5OH. The mean C5OH value for
      derivatized and non-derivatized methods was 2.80 and 2.67 MUmol/l, respectively.
      Reported data from other specimens showed a similar trend in derivatized vs. non
      derivatized assay results. Differences in C5OH quantitative values were observed
      among laboratories using different internal standards. CONCLUSIONS: C5OH MS/MS
      measurements in DBS assays varied by method and the choice of internal standards.
      The use of NSQAP's DBS materials allows harmonization of C5OH measurements by
      newborn screening laboratories worldwide.

PMID- 21185275
TI  - Determination of cortisol production rates with contemporary liquid
      chromatography-mass spectrometry to measure cortisol-d(3) dilution after infusion
      of deuterated tracer.
AB  - OBJECTIVES: Measurement of 24-h cortisol production rate (CPR) using steady-state
      infusion of deuterated cortisol and analysis of stable-isotope dilution by MS is
      a valuable tool to examine hypothalamic-pituitary-adrenal axis activity in
      humans. We have developed and validated an improved method for measuring cortisol
      dilution with contemporary LC-MS technology. DESIGN AND METHODS: Plasma samples
      and calibrators were extracted with ethylacetate. LC-MS was performed with a
      Surveyor HPLC and TSQ Quantum triple-quadrupole mass spectrometer equipped with
      an atmospheric pressure chemical ionization (APCI) source. RESULTS: Selectivity
      was improved over previous methods via elimination of an interferent identified
      as 20beta-dihydrocortisol. The LLOQ for cortisol-d(3) was 2.73nmol/L and LOD
      1.37nmol/L. Plasma calibrators were linear over the concentration range 1.5-10%
      cortisol-d(3), with correlation coefficients >0.995. CONCLUSIONS: This APCI LC-MS
      method offers simplified sample work-up and analysis and enables selective
      detection of the low concentration of cortisol-d(3) infused for determination of
      24-h CPR.

PMID- 21185276
TI  - Pregnancy associated plasma protein-A (PAPP-A) is not a marker of the vulnerable
      atherosclerotic plaque.
AB  - OBJECTIVE: To investigate if pregnancy associated plasma protein-A (PAPP-A) was
      present in the vulnerable plaque, and if not, to find alternative hypothesis for
      the release of PAPP-A. DESIGN AND METHODS: Vulnerable plaques and control tissues
      were examined by immunohistochemistry. Volunteers and patients with non
      atherosclerotic disease were examined for release of PAPP-A during ischemia and
      medical treatment. Non-atherosclerotic tissue samples were examined after
      incubation with heparins. RESULTS: We were not able to detect PAPP-A in
      vulnerable plaques. Patients and volunteers experiencing ischemic events without
      atherosclerotic lesions only had elevated PAPP-A when treated with heparin. When
      tissue from normal artery wall was incubated with heparin, PAPP-A was eluted.
      This was not the case for non-arterial tissue samples. CONCLUSION: Elevation of
      PAPP-A in patients with acute coronary syndromes seems to be caused by heparin
      induced release of PAPP-A from the arterial wall and not due to excretion from
      vulnerable plaques.

PMID- 21185277
TI  - A simple and inexpensive automated technique for measurement of serum
      nitrite/nitrate.
AB  - OBJECTIVE: We described an automated technique for measurement of serum
      nitrite/nitrate (NO(x)) using the Cobas Mira clinical chemistry analyzer. DESIGN
      AND METHODS: NO(x) was measured by the modified Griess method. Precision,
      accuracy, linearity, instrument carry-over and lower limit of quantitation (LLOQ)
      were assessed. RESULTS: The automated technique for measurement of serum NO(x)
      was linear, precise, and accurate. It has a LLOQ of 2.0 MUmol/L. CONCLUSION:
      Serum NO(x) measured by the modified Griess method can be applied easily to the
      Cobas Mira clinical chemistry analyzer.

PMID- 21185278
TI  - Bmpr1a signaling plays critical roles in palatal shelf growth and palatal bone
      formation.
AB  - Cleft palate, including submucous cleft palate, is among the most common birth
      defects in humans. While overt cleft palate results from defects in growth or
      fusion of the developing palatal shelves, submucous cleft palate is characterized
      by defects in palatal bones. In this report, we show that the Bmpr1a gene,
      encoding a type I receptor for bone morphogenetic proteins (Bmp), is
      preferentially expressed in the primary palate and anterior secondary palate
      during palatal outgrowth. Following palatal fusion, Bmpr1a mRNA expression was
      upregulated in the condensed mesenchyme progenitors of palatal bone. Tissue
      specific inactivation of Bmpr1a in the developing palatal mesenchyme in mice
      caused reduced cell proliferation in the primary and anterior secondary palate,
      resulting in partial cleft of the anterior palate at birth. Expression of Msx1
      and Fgf10 was downregulated in the anterior palate mesenchyme and expression of
      Shh was downregulated in the anterior palatal epithelium in the Bmpr1a
      conditional mutant embryos, indicating that Bmp signaling regulates mesenchymal
      epithelial interactions during palatal outgrowth. In addition, formation of the
      palatal processes of the maxilla was blocked while formation of the palatal
      processes of the palatine was significantly delayed, resulting in submucous cleft
      of the hard palate in the mutant mice. Our data indicate that Bmp signaling plays
      critical roles in the regulation of palatal mesenchyme condensation and
      osteoblast differentiation during palatal bone formation.

PMID- 21185279
TI  - The Pou5f1/Pou3f-dependent but SoxB-independent regulation of conserved enhancer
      N2 initiates Sox2 expression during epiblast to neural plate stages in
      vertebrates.
AB  - The transcription factor Sox2 is a core component of the pluripotency control
      circuits in the early embryo, and later controls many aspects of neural
      development. Here, we demonstrate that Sox2 expression in the epiblast (mouse
      blastoderm) and anterior neural plate (ANP) is determined by the upstream
      enhancer N2. The mouse enhancer N2 exhibits strong activity in mouse ES cells,
      epiblast and ANP, and is regulated correctly in chicken and zebrafish embryos.
      Targeted deletion of this enhancer in mouse embryos caused a large reduction of
      Sox2 expression to 10% of that of wild-type levels in epiblast and ANP. However,
      this was tolerated by mouse embryo, probably due to functional compensation by
      Sox3. The activity of enhancer N2 depends on phylogenetically conserved bipartite
      POU factor-binding motifs in a 73-bp core sequence that function synergistically,
      but this activation does not involve Sox2. The major POU factor expressed at the
      epiblastic stage is Pou5f1 (Oct3/4), while those in the anterior neural plate are
      Pou3f factors (Oct6, Brn2 etc.). These factors are gradually exchanged during the
      transition from epiblast to ANP stages in mouse embryos and epiblast stem cells
      (EpiSC). Consistently, enhancer N2 activity changes from full Pou5f1 dependence
      to Pou3f dependence during the development of neural plate cells (NPC) from
      EpiSC, as assessed by specific POU factor knockdown in these cells. Zebrafish
      mutant embryos completely devoid of Pou5f1 activity failed to activate enhancer
      N2 and to express Sox2 in the blastoderm and ANP, and these defects were rescued
      by exogenous supply of pou5f1. Previously, Pou5f1-Sox2 synergism-dependent Sox2
      activation through enhancer SRR2 in ES cells has been highlighted, but this
      mechanism is limited to ES cells and amniotes. In contrast, the enhancer N2
      mediated, POU factor-dependent activation of Sox2, without involvement of Sox2,
      is a phylogenetically conserved core mechanism that functions in gene regulatory
      networks at early embryonic stages.

PMID- 21185280
TI  - Synovial joint formation requires local Ext1 expression and heparan sulfate
      production in developing mouse embryo limbs and spine.
AB  - Heparan sulfate proteoglycans (HSPGs) regulate a number of major developmental
      processes, but their roles in synovial joint formation remain unknown. Here we
      created conditional mouse embryo mutants lacking Ext1 in developing joints by
      mating Ext1(f/f) and Gdf5-Cre mice. Ext1 encodes a subunit of the Ext1/Ext2 Golgi
      associated protein complex responsible for heparan sulfate (HS) synthesis. The
      proximal limb joints did form in the Gdf5-Cre;Ext1(f/f) mutants, but contained an
      uneven articulating superficial zone that expressed very low lubricin levels. The
      underlying cartilaginous epiphysis was deranged as well and displayed random
      patterns of cell proliferation and matrillin-1 and collagen IIA expression,
      indicative of an aberrant phenotypic definition of the epiphysis itself. Digit
      joints were even more affected, lacked a distinct mesenchymal interzone and were
      often fused likely as a result of local abnormal BMP and hedgehog activity and
      signaling. Interestingly, overall growth and lengthening of long bones were also
      delayed in the mutants. To test whether Ext1 function is needed for joint
      formation at other sites, we examined the spine. Indeed, entire intervertebral
      discs, normally composed by nucleus pulposus surrounded by the annulus fibrosus,
      were often missing in Gdf5-Cre;Ext1(f/f) mice. When disc remnants were present,
      they displayed aberrant organization and defective joint marker expression.
      Similar intervertebral joint defects and fusions occurred in Col2-Cre;beta
      catenin(f/f) mutants. The study provides novel evidence that local Ext1
      expression and HS production are needed to maintain the phenotype and function of
      joint-forming cells and coordinate local signaling by BMP, hedgehog and Wnt/beta
      catenin pathways. The data indicate also that defects in joint formation
      reverberate on, and delay, overall long bone growth.

PMID- 21185282
TI  - Radial glia regulate Cajal-Retzius cell positioning in the early embryonic
      cerebral cortex.
AB  - The organization of neocortex, along its radial axis, into a six-layered
      structure is one of the most exquisite features of the brain. Because of their
      strategic localization in the marginal zone, and their expression of reelin, a
      signal that controls spatial ordering of cortical layers, Cajal-Retzius (C-R)
      cells play a crucial role in cortical patterning along this axis. Yet, it remains
      less well understood how C-R cell targeting itself is regulated. At the onset of
      corticogenesis when C-R cells first arrive in the cortex via tangential
      migration, radial glia (RG) are the main cell type present. This suggests that RG
      may play a role in C-R cell localization. To test this, we used genetic
      approaches to perturb RG scaffold during early corticogenesis. We found that
      disrupting RG endfoot adhesion to basal lamina consistently results in C-R cell
      displacement. These displacements do not appear to result from primary defects in
      neural progenitor cell proliferation, deficits in the meninges or basement
      membrane, or cell autonomous defects in C-R cells. Instead, they show close
      temporal and spatial correlation with RG endfoot retraction. Moreover, ablation
      of RG via cell cycle blockade similarly results in local displacement of C-R
      cells. These lines of evidence thus indicate that, during early corticogenesis,
      RG play a primary role in regulating spatial targeting of C-R cells. Since RG are
      also neural progenitors as well as neuronal migration scaffolds, these findings
      suggest that, during nervous system development, neuroepithelial stem cells may
      not only be responsible for generating a diverse array of neuronal cell types and
      facilitating their radial migration. They may also, through regulating the
      placement of guidepost cells, coordinate spatial patterning of the nervous system
      along its radial axis.

PMID- 21185281
TI  - Hand2 function in second heart field progenitors is essential for cardiogenesis.
AB  - Cardiogenesis involves the contributions of multiple progenitor pools, including
      mesoderm-derived cardiac progenitors known as the first and second heart fields.
      Disruption of genetic pathways regulating individual subsets of cardiac
      progenitors likely underlies many forms of human cardiac malformations. Hand2 is
      a member of the basic helix loop helix (bHLH) family of transcription factors and
      is expressed in numerous cell lineages that contribute to the developing heart.
      However, the early embryonic lethality of Hand2-null mice has precluded lineage
      specific study of its function in myocardial progenitors. Here, we generated and
      used a floxed allele of Hand2 to ablate its expression in specific cardiac cell
      populations at defined developmental points. We found that Hand2 expression
      within the mesoderm-derived second heart field progenitors was required for their
      survival and deletion in this domain recapitulated the complete Hand2-null
      phenotype. Loss of Hand2 at later stages of development and in restricted domains
      of the second heart field revealed a spectrum of cardiac anomalies resembling
      forms of human congenital heart disease. Molecular analyses of Hand2 mutant cells
      revealed several genes by which Hand2 may influence expansion of the cardiac
      progenitors. These findings demonstrate that Hand2 is essential for survival of
      second heart field progenitors and that the graded loss of Hand2 function in this
      cardiac progenitor pool can cause a spectrum of congenital heart malformation.

PMID- 21185283
TI  - Cell proliferation in the absence of E2F1-3.
AB  - E2F transcription factors regulate the progression of the cell cycle by
      repression or transactivation of genes that encode cyclins, cyclin dependent
      kinases, checkpoint regulators, and replication proteins. Although some E2F
      functions are independent of the Retinoblastoma tumor suppressor (Rb) and related
      family members, p107 and p130, much of E2F-mediated repression of S phase entry
      is dependent upon Rb. We previously showed in cultured mouse embryonic
      fibroblasts that concomitant loss of three E2F activators with overlapping
      functions (E2F1, E2F2, and E2F3) triggered the p53-p21(Cip1) response and caused
      cell cycle arrest. Here we report on a dramatic difference in the requirement for
      E2F during development and in cultured cells by showing that cell cycle entry
      occurs normally in E2f1-3 triply-deficient epithelial stem cells and progenitors
      of the developing lens. Sixteen days after birth, however, massive apoptosis in
      differentiating epithelium leads to a collapse of the entire eye. Prior to this
      collapse, we find that expression of cell cycle-regulated genes in E2F-deficient
      lenses is aberrantly high. In a second set of experiments, we demonstrate that
      E2F3 ablation alone does not cause abnormalities in lens development but rescues
      phenotypic defects caused by loss of Rb, a binding partner of E2F known to
      recruit histone deacetylases, SWI/SNF and CtBP-polycomb complexes,
      methyltransferases, and other co-repressors to gene promoters. Together, these
      data implicate E2F1-3 in mediating transcriptional repression by Rb during cell
      cycle exit and point to a critical role for their repressive functions in cell
      survival.

PMID- 21185284
TI  - Epithelial Wnt/beta-catenin signaling regulates palatal shelf fusion through
      regulation of Tgfbeta3 expression.
AB  - The canonical Wnt/beta-catenin signaling plays essential role in development and
      diseases. Previous studies have implicated the canonical Wnt/beta-catenin
      signaling in the regulation of normal palate development, but functional Wnt/beta
      catenin signaling and its tissue-specific activities remain to be accurately
      elucidated. In this study, we show that functional Wnt/beta-catenin signaling
      operates primarily in the palate epithelium, particularly in the medial edge
      epithelium (MEE) of the developing mouse palatal shelves, consistent with the
      expression patterns of beta-catenin and several Wnt ligands and receptors.
      Epithelial specific inactivation of beta-catenin by the K14-Cre transgenic allele
      abolishes the canonical Wnt signaling activity in the palatal epithelium and
      leads to an abnormal persistence of the medial edge seam (MES), ultimately
      causing a cleft palate formation, a phenotype resembling that in Tgfbeta3 mutant
      mice. Consistent with this phenotype is the down-regulation of Tgfbeta3 and
      suppression of apoptosis in the MEE of the beta-catenin mutant palatal shelves.
      Application of exogenous Tgfbeta3 to the mutant palatal shelves in organ culture
      rescues the midline seam phenotype. On the other hand, expression of stabilized
      beta-catenin in the palatal epithelium also disrupts normal palatogenesis by
      activating ectopic Tgfbeta3 expression in the palatal epithelium and causing an
      aberrant fusion between the palate shelf and mandible in addition to severely
      deformed palatal shelves. Collectively, our results demonstrate an essential role
      for Wnt/beta-catenin signaling in the epithelial component at the step of palate
      fusion during palate development by controlling the expression of Tgfbeta3 in the
      MEE.

PMID- 21185285
TI  - Developmental regulation of MURF ubiquitin ligases and autophagy proteins nbr1,
      p62/SQSTM1 and LC3 during cardiac myofibril assembly and turnover.
AB  - The striated muscle-specific tripartite motif (TRIM) proteins TRIM63/MURF1,
      TRIM55/MURF2 and TRIM54/MURF3 can function as ubiquitin E3 ligases in ubiquitin
      mediated muscle protein turnover. Despite their well-characterised roles in
      muscle atrophy, the dynamics of MURF expression in the development and early
      postnatal adaptation of striated muscle is largely unknown. Here, we show that
      MURF2 is expressed at the very onset of mouse cardiac differentiation at
      embryonic day 8.5, and represents a sensitive marker for differentiating
      myocardium. During cardiac development, expression shifts from the 50 kDa to the
      60 kDa A-isoform, which dominates postnatally. In contrast, MURF1 shows strong
      postnatal upregulation and MURF3 is not significantly expressed before birth.
      MURF2 expression parallels that of the autophagy-associated proteins LC3,
      p62/SQSTM1 and nbr1. SiRNA knockdown of MURF2 in neonatal rat cardiomyocytes
      disrupts posttranslational microtubule modification and myofibril assembly, and
      is only partly compensated by upregulation of MURF3 but not MURF1. Knockdown of
      both MURF2 and MURF3 severely disrupts the formation of ordered Z- and M-bands,
      likely by perturbed tubulin dynamics. These results suggest that ubiquitin
      mediated protein turnover and MURF2 in particular play an unrecognised role in
      the earliest steps of heart muscle differentiation, and that partial
      complementation of MURF2 deficiency is afforded by MURF3.

PMID- 21185286
TI  - Metabolic sugar signal promotes Arabidopsis meristematic proliferation via G2.
AB  - Most organs in higher plants are generated postembryonically from the meristems,
      which harbor continuously dividing stem cells throughout a plant's life cycle. In
      addition to developmental regulations, mitotic activities in the meristematic
      tissues are modulated by nutritional cues, including carbon source availability.
      Here we further analyze the relationship between the sugar signal and seedling
      meristem establishment, taking advantage of our previous observation that
      exogenously supplied metabolic sugars can rescue the meristem growth arrest
      phenotype of the Arabidopsis stip mutant seedlings. Our results show that
      metabolic sugars reactivate the stip meristems by activating the expression of
      key cell cycle regulators, and therefore, promoting G2 to M transition in
      Arabidopsis meristematic tissues. One of the early events in this process is the
      transcriptional repression of TSS, a genetic suppressor of the stip mutations, by
      sugar signals, suggesting that TSS may act as an integrator of developmental and
      nutritional signals in regulating meristematic proliferation. We also present
      evidence that metabolic sugar signals are required for the activation of mitotic
      entry during de novo meristem formation from G2 arrested cells. Our observations,
      together with the recent findings that nutrient deprivation leads to G2 arrest of
      animal germline stem cells, suggest that carbohydrate availability-regulated G2
      to M transition may represent a common mechanism in stem cell division regulation
      in multicellular organisms.

PMID- 21185288
TI  - The Escherichia coli metal-binding chaperone SlyD interacts with the large
      subunit of [NiFe]-hydrogenase 3.
AB  - The multi-step biosynthesis of the [NiFe]-hydrogenase enzyme involves a variety
      of accessory proteins. To further understand this process, a Strep-tag II variant
      of the large subunit of Escherichia coli hydrogenase 3, HycE, was constructed to
      enable isolation of protein complexes. A complex with SlyD, a chaperone protein
      implicated in hydrogenase production through association with the nickel-binding
      accessory protein HypB, was observed. A SlyD-HycE interaction preceding both iron
      and nickel insertion to the enzyme was detected, mediated by the chaperone domain
      of SlyD, and independent of HypB. These results support a model of several roles
      for SlyD during hydrogenase maturation.

PMID- 21185287
TI  - Quantification and cell-to-cell variation of vascular endothelial growth factor
      receptors.
AB  - The vascular endothelial growth factor receptors (VEGFR) play a significant role
      in angiogenesis, the formation of new blood vessels from existing vasculature.
      Systems biology offers promising approaches to better understand angiogenesis by
      computational modeling the key molecular interactions in this process. Such
      modeling requires quantitative knowledge of cell surface density of pro
      angiogenic receptors versus anti-angiogenic receptors, their regulation, and
      their cell-to-cell variability. Using quantitative fluorescence, we
      systematically characterized the endothelial surface density of VEGFRs and
      neuropilin-1 (NRP1). We also determined the role of VEGF in regulating the
      surface density of these receptors. Applying cell-by-cell analysis revealed
      heterogeneity in receptor surface density and VEGF tuning of this heterogeneity.
      Altogether, we determine inherent differences in the surface expression levels of
      these receptors and the role of VEGF in regulating the balance of anti-angiogenic
      or modulatory (VEGFR1) and pro-angiogenic (VEGFR2) receptors.

PMID- 21185289
TI  - The LKB1/AMPK polarity pathway.
AB  - The LKB1 tumor suppressor kinase is an activator of the AMP-activated protein
      kinase (AMPK), a metabolic gauge that responds to variations of cellular
      energetic levels by favoring catabolic versus anabolic processes. Recent studies
      have provided substantial evidence that LKB1 and AMPK control cell polarity from
      invertebrates to mammals. This review examines how the LKB1-AMPK pathway, in
      conjunction with other positional signals, converts energy-sensing information
      into the activation of Myosin II to maintain epithelial-cell architecture but
      also to complete cell division. This molecular link between polarity and
      metabolism may constitute an ancient stress-response protective mechanism that
      was co-opted for tumor suppression during evolution.

PMID- 21185290
TI  - Evolution of GnRH: diving deeper.
AB  - Gonadotropin-releasing hormone (GnRH) plays a central role in vertebrate
      reproduction. The evolutionary origin of this neuropeptide and its receptor is
      not obvious, but the advent of genomics makes it possible to examine the roots of
      GnRH and delve deeper into its ancestral relationships. New peptide sequences
      identified in invertebrates from annelids to tunicates reveal GnRH-like peptides
      of 10-12 amino acids. Structural conservation suggests homology between the 15
      known invertebrate peptides and the 15 known vertebrate GnRHs. The functions of
      the invertebrate GnRH-like peptides are not necessarily related to reproduction.
      We suggest that structurally related families of invertebrate peptides including
      corazonin and adipokinetic hormone (AKH) form a superfamily of neuropeptides with
      the GnRH family. GnRH receptors have also been identified in invertebrates from
      annelids to tunicates suggesting that the origin of GnRH and its receptor extends
      deep in evolution to the origin of bilaterian animals. To resolve the
      relationship of invertebrate and vertebrate receptors, we conducted large-scale
      phylogenetic analysis using maximum likelihood. The data support a superfamily
      that includes GnRH, AKH and corazonin receptors derived from both published
      sequences and unpublished gene model predictions. Closely related to the GnRHR
      superfamily is the vasopressin/oxytocin superfamily of receptors. Phylogenetic
      analysis suggests a shared ancestry with deep roots. A functional role for GnRH
      in vertebrates or invertebrates leads to questions about the evolutionary origin
      of the pituitary. Our analysis suggests a functioning pituitary was the result of
      genomic duplications in early vertebrates.

PMID- 21185291
TI  - Oxidative stress elicited by insecticides: a role for the adipokinetic hormone.
AB  - Adipokinetic hormones (AKHs) are insect neuropeptides responding to stress
      situations including oxidative stress. Two insecticides - endosulfan and
      malathion - were used to elicit oxidative stress conditions in the firebug
      Pyrrhocoris apterus, and the physiological functions of AKHs and their ability to
      activate protective antioxidative reactions were studied. The insecticide
      treatments elicited only a slight increase of the AKH level in CNS, but more
      intensive increase in haemolymph, which indicates an immediate involvement of AKH
      in the stress response. The treatment also resulted in a significant increase of
      catalase activity in the bug's body and depletion of the reduced glutathione pool
      in the haemolymph, however, co-application of the insecticides with the AKH (80
      pmol) reduced the effect. It has also been found that co-application of the
      insecticides with AKH increased significantly the bug mortality compared to that
      induced by the insecticides alone. This enhanced effect of the insecticides
      probably resulted from the stimulatory role of AKH on bug metabolism: the carbon
      dioxide production was increased significantly after the co-treatment by AKH with
      insecticides compared to insecticide treatment alone. It was hypothesized that
      the increased metabolic rate could intensify the insecticide action by an
      accelerated rate of exchange of metabolites accompanied by faster penetration of
      insecticides into tissues.

PMID- 21185293
TI  - Growth hormone promotes the survival of retinal cells in vivo.
AB  - Growth hormone (GH) is synthesized and present in the developing chick retina,
      where it may have local actions in retinal cell differentiation similar to those
      of conventional growth factors. We have previously shown that retinal GH has
      neuroprotective effects in retinal ganglion cells. In this paper, we extend our
      earlier functional studies by examining the in vivo effects of a GH siRNA (NR-cGH
      1) after microinjection into the eye cup of the developing chick embryo in ovo.
      We show that intra-vitreous cGH siRNA lowers both GH mRNA and insulin-like growth
      factor-1 (IGF-1) mRNA levels in the retina in vivo, and concomitantly elevates
      the numbers of apoptotic cells in the retina. These effects are apparent 6h after
      treatment, and persist for at least 24h. The apoptotic cells induced by GH
      withdrawal were primarily located close to the optic fissure of the developing
      eye, and were distributed in clusters, suggesting that there are sub-populations
      of retinal cells that are particularly susceptible to apoptotic stimuli. These
      results support our view that a GH/IGF-1 axis in retinal cells regulates retinal
      cell survival in vivo.

PMID- 21185292
TI  - Molecular characterization and brain distribution of the progesterone receptor in
      whiptail lizards.
AB  - Progesterone and its nuclear receptor are critical in modulating reproductive
      physiology and behavior in female and male vertebrates. Whiptail lizards (genus
      Cnemidophorus) are an excellent model system in which to study the evolution of
      sexual behavior, as both the ancestral and descendent species exist. Male-typical
      sexual behavior is mediated by progesterone in both the ancestral species and the
      descendant all-female species, although the molecular characterization and
      distribution of the progesterone receptor protein throughout the reptilian brain
      is not well understood. To better understand the gene targets and ligand binding
      properties of the progesterone receptor in whiptails, we cloned the promoter and
      coding sequence of the progesterone receptor and analyzed the predicted protein
      structure. We next determined the distribution of the progesterone receptor
      protein and mRNA throughout the brain of Cnemidophorus inornatus and
      Cnemidophorus uniparens by immunohistochemistry and in situ hybridization. We
      found the progesterone receptor to be present in many brain regions known to
      regulate social behavior and processing of stimulus salience across many
      vertebrates, including the ventral tegmental area, amygdala, nucleus accumbens
      and several hypothalamic nuclei. Additionally, we quantified immunoreactive cells
      in the preoptic area and ventromedial hypothalamus in females of both species and
      males of the ancestral species. We found differences between both species and
      across ovarian states. Our results significantly extend our understanding of
      progesterone modulation in the reptilian brain and support the important role of
      the nuclear progesterone receptor in modulating sexual behavior in reptiles and
      across vertebrates.

PMID- 21185294
TI  - Presence of pituitary adenylate cyclase-activating polypeptide (PACAP) in the
      plasma and milk of ruminant animals.
AB  - Milk contains a variety of proteins and peptides that possess biological
      activity. Growth factors, such as growth hormone, insulin-like, epidermal and
      nerve growth factors are important milk components which may regulate growth and
      differentiation in various neonatal tissues and also those of the mammary gland
      itself. We have recently shown that pituitary adenylate cyclase-activating
      polypeptide (PACAP), an important neuropeptide with neurotrophic actions, is
      present in the human milk in much higher concentration than in the plasma of
      lactating women. Investigation of growth factors in the milk of domestic animals
      is of utmost importance for their nutritional values and agricultural
      significance. Therefore, the aim of the present study was to determine the
      presence and concentration of PACAP in the plasma and milk of three ruminant
      animal species. Furthermore, the presence of PACAP and its specific PAC1 receptor
      were investigated in the mammary glands. Radioimmunoassay measurements revealed
      that PACAP was present in the plasma and the milk of the sheep, goat and the cow
      in a similar concentration to that measured previously in humans. PACAP38-like
      immunoreactivity (PACAP38-LI) was 5-20-fold higher in the milk than in the plasma
      samples of the respective animals, a similar serum/milk ratio was found in all
      the three species. The levels did not show significant changes within the
      examined 3-month-period of lactation after delivery. Similar PACAP38-LI was
      measured in the homogenates of the sheep mammary gland samples taken 7 and 30
      days after delivery. PAC1 receptor expression was detected in these udder
      biopsies by fluorescent immunohistochemistry suggesting that this peptide might
      have an effect on the mammary glands themselves. These data show that PACAP is
      present in the milk of various ruminant domestic animal species at high
      concentrations, the physiological implications of which awaits further
      investigation.

PMID- 21185295
TI  - Inhibiting roles of melanin-concentrating hormone for skin pigment dispersion in
      barfin flounder, Verasper moseri.
AB  - Barfin flounders change their surface color pattern to match their background. We
      have reported evidence of the association between hormones and body color changes
      in this fish. First, bolus intraperitoneal injection with melanin-concentrating
      hormone (MCH) immediately turned the skin color pale, while injection with
      melanocyte-stimulating hormone (MSH) did not change the skin color. Second, gene
      expression levels of MCH change in response to background color, while those of
      MSH do not. We also reported the expression of an MCH receptor gene (Mch-r2) in
      the skin of this fish. In this study, we aimed to further evaluate the roles of
      MCH in skin color change. First, long-term adaptation of adult barfin flounder to
      black or white background colors induced significantly different pigment
      migration patterns in both melanophores and xanthophores (P<0.05). However,
      continuous intraperitoneal injection with MCH did not influence chromatophore
      proliferation. Then, using in vitro experiments, we found that MCH aggregates
      both melanophores and xanthophores, and inhibits the pigment-dispersing activity
      of MSH in a similar manner. Finally, we identified transcripts of Mch-r2 in cells
      isolated from both melanophores and xanthophores. Taken together, the evidence
      suggests that MCH aggregates pigments via MCH-R2 in concert with the nervous
      system by overcoming the melanin-dispersing activities of MSH in barfin flounder.

PMID- 21185296
TI  - Pre- and postnatal bisphenol A treatment results in persistent deficits in the
      sexual behavior of male rats, but not female rats, in adulthood.
AB  - Perinatal administration of the endocrine disruptor bisphenol A (BPA) reportedly
      inhibits the sexual behavior of sexually naive adult male rats. In order to
      evaluate the effects of BPA administration during early development on later
      reproductive behavior, we administered one of five doses of bisphenol A daily to
      pregnant female rats throughout gestation and lactation, and quantified the
      appetitive and consummatory sexual behaviors of the resultant male and female
      offspring over multiple sexual encounters in adulthood. Males receiving low dose
      perinatal BPA (50 MUg/kg bw/day) showed persistent deficits in sexual behavior in
      adulthood. Males receiving the highest dose (5 mg/kg bw/day), however, were
      indistinguishable from controls with respect to consummatory sexual behaviors but
      showed decreased latencies to engage in those behaviors when sexually naive, with
      significant non-linear, or U-shaped, dose-response relationships observed on the
      first and last day of testing. Adult female sexual behavior was not affected by
      early BPA administration at any dose tested. These results are consistent with
      previous reports that BPA exerts behavioral effects especially at low doses, and
      further indicates that BPA can cause lasting impairment of sexual behavior in
      males, but does not alter the normal development of female appetitive or
      consummatory sexual behaviors. To our knowledge, this is the first report
      indicating that adult sexual performance is impaired in sexually experienced
      animals following perinatal exposure to bisphenol A.

PMID- 21185297
TI  - Hypothalamic vasopressin response to stress and various physiological stimuli:
      visualization in transgenic animal models.
AB  - Arginine vasopressin (AVP) is involved in the homeostatic responses numerous life
      threatening conditions, for example, the promotion of water conservation during
      periods of dehydration, and the activation of the hypothalamo-pituitary adrenal
      axis by emotional stress. Recently, we generated new transgenic animals that
      faithfully express an AVP-enhanced green fluorescent protein (eGFP) fusion gene
      in the paraventricular nucleus (PVN), the supraoptic nucleus (SON) and the
      suprachiasmatic nucleus (SCN) of the hypothalamus. In these transgenic rats,
      marked increases in eGFP fluorescence and fusion gene expression were observed in
      the magnocellular division of the PVN and the SON, but not the SCN, after osmotic
      challenges, such as dehydration and salt loading, and both acute and chronic
      nociceptive stimuli. In the parvocellular division of the PVN, eGFP expression
      was increased after acute and chronic pain, bilateral adrenalectomy, endotoxin
      shock and restraint stress. In the extra-hypothalamic areas of the brain, eGFP
      expression was induced in the locus coeruleus after the intracerebroventricular
      administration of colchicine. Next, we generated another transgenic rat that
      expresses a fusion gene comprised of c-fos promoter-enhancer sequences driving
      the expression of monomeric red fluorescent protein 1 (mRFP1). In these
      transgenic rats, abundant nuclear fluorescence of mRFP1 was observed in the PVN,
      the SON and other osmosensitive areas after acute osmotic stimulation. Finally,
      we generated a double transgenic rat that expresses both the AVP-eGFP and c-fos
      mRFP1 fusion genes. In this double transgenic rat, we have observed nuclear mRFP1
      fluorescence in eGFP-positive neurons after acute osmotic stimulation. These
      unique transgenic rats provide an exciting new tool to examine neuroendocrine
      responses to physiological and stressful stimuli in both in vivo and in vitro
      preparations.

PMID- 21185298
TI  - Poly(ADP-ribose) polymerase plays a differential role in DNA damage-response and
      cell death pathways in Trypanosoma cruzi.
AB  - Poly(ADP-ribosyl)ation is a post-translational modification of proteins. Poly(ADP
      ribose) polymerase (PARP) and poly(ADP-ribose) glycohydrolase (PARG) are the
      enzymes responsible for poly(ADP-ribose) (PAR) polymer metabolism and are present
      in most higher eukaryotes. The best understood role of PARP is the maintenance of
      genomic integrity either via promotion of DNA repair at low levels of genotoxic
      stress or via promotion of cell death at higher levels of damage. The unicellular
      eukaryote Trypanosoma cruzi, as opposed to humans and other organisms, has only
      one PARP (TcPARP) and one PARG (TcPARG). In the present study we show that under
      different DNA-damaging agents (H(2)O(2) or UV-C radiation) TcPARP is activated
      and translocated from the cytosol to the nucleus, while TcPARG always shows a
      nuclear localisation. Parasites in the presence of PARP or PARG inhibitors, as
      well as parasites over-expressing either TcPARP or TcPARG, suggested that PAR
      metabolism could be involved in different phases of cell growth, even in the
      absence of DNA damage. We also believe that we provide the first reported
      evidence that different proteins could be poly(ADP-ribosyl)ated in response to
      different stimuli, leading to different cell death pathways.

PMID- 21185299
TI  - Production of rabbit monoclonal antibodies against mouse embryonic stem cells and
      identification of pluripotency-associated surface antigens.
AB  - Embryonic stem (ES) cells are pluripotent stem cells derived from the inner cell
      mass of the blastocyst. ES cell surface molecules are important for the
      identification, labeling, sorting, quality control and functional studies of ES
      cells. Currently, knowledge of ES surface molecules is limited. To identify new
      surface molecules, we generated a panel of rabbit monoclonal antibodies (rMabs)
      against mouse ES (mES) cells. We identified three monoclonal antibodies that
      interact with molecules on the mES cell surface and found that the expression of
      their respective antigens decreased upon mES cell differentiation. The antigen of
      the rMab ZjuESrMab29 was identified as granulocyte macrophage colony-stimulating
      factor receptor alpha (GM-CSFR alpha) by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). This study demonstrated that rabbit monoclonal antibody
      production via whole-cell immunization could be a practical method for the
      discovery of stem cell surface antigens.

PMID- 21185300
TI  - A multiplex assay for the quantification of antibody responses in Staphylococcus
      aureus infections in mice.
AB  - Staphylococcus aureus causes a variety of infections. Knowledge about the
      physiological role of most S. aureus antigens in colonization and infection is
      only limited. This can be studied by measuring antigen-specific antibody
      responses. In this study, we optimized the multiplex microsphere bead-based flow
      cytometry technique for mouse serum samples. We analysed immunoglobulin G (IgG)
      levels directed against 26 S. aureus proteins in a single small-volume mouse
      serum sample. We assessed possible cross reactivity. Furthermore, we analysed
      serum samples from mice with different types of S. aureus infections caused by
      different S. aureus strains. The results show that cross reactivity between
      proteins on microspheres and serum antibodies towards other proteins was limited.
      We found that lung-infected mice had a higher and broader IgG response than skin
      infected mice. Clearly, the site of infection influences the IgG profile. Next,
      we compared sera from mice with intravenously-induced bacteraemia caused by
      different S. aureus strains. We showed different IgG responses depending on the
      causing S. aureus strain. It is concluded that the bead-based multiplex S. aureus
      antibody assay can be successfully applied to determine the immunogenicity of
      different S. aureus proteins in relation to the site of infection and the S.
      aureus strain causing the infection.

PMID- 21185301
TI  - Identification of IgG(1) variants with increased affinity to FcgammaRIIIa and
      unaltered affinity to FcgammaRI and FcRn: comparison of soluble receptor-based
      and cell-based binding assays.
AB  - Clinical response to the anti-CD20 antibody rituximab has been demonstrated to
      correlate with the polymorphism in the FcgammaRIIIa receptor where patients
      homozygous for the higher affinity V158 allotype showed a better response rate.
      This finding suggests that engineering of anti-CD20 for increased FcgammaRIIIa
      affinity could result in improved clinical outcome. To identify variants with
      increased affinity to FcgammaRIIIa, we developed quantitative assays using
      soluble receptors as well as engineered cell lines expressing FcgammaRI or
      FcgammaRIIIa on the cell surface. We assayed a set of anti-CD20 IgG(1) variants
      that had identical Fab regions, but alterations in the Fc regions, in both the
      soluble receptor-based and cell-based FcgammaRIIIa binding assays. We obtained
      similar relative binding affinity increases and assay precisions. The increase in
      affinity for FcgammaRIIIa correlated with the increase in activity in the
      antibody-dependent cellular cytotoxicity assay. These variants had unaltered
      FcgammaRI binding. In addition to Fcgamma receptors, IgG also binds to FcRn, the
      receptor responsible for the long circulating half-life of IgG. The mutations in
      the anti-CD20 variants were previously found not to affect FcRn binding in the
      soluble receptor-based assays; consequently, we used anti-Her2 variants with
      different binding affinities to FcRn to study FcRn binding assays. We generated a
      cell line expressing FcRn on the cell surface to measure IgG binding and obtained
      similar ranking of these anti-Her2 variants in the cell-based and the soluble
      receptor-based FcRn binding assays. In conclusion, both the soluble receptor
      based and cell-based binding assays can be used to identify IgG(1) variants with
      increased affinity to FcgammaRIIIa and unaltered affinity to FcgammaRI and FcRn.

PMID- 21185302
TI  - High-affinity amphipathic modulators of amyloid fibril nucleation and elongation.
AB  - The misfolding and aggregation of proteins to form amyloid fibrils are associated
      with a number of debilitating, age-related diseases. Many of the proteins that
      form amyloid in vivo are lipid-binding proteins, accounting for the significant
      impact of lipids on the rate of formation and morphology of amyloid fibrils. To
      systematically investigate the effect of lipid-like compounds, we screened a
      range of amphipathic lipids and detergents for their effect on amyloid fibril
      formation by human apolipoprotein (apo) C-II. The initial screen, conducted using
      a set of amphiphiles at half critical micelle concentration, identified several
      activators and inhibitors that were selected for further analysis. Sedimentation
      analysis and circular dichroism studies of apoC-II at low, non-fibril-forming
      concentrations (0.05 mg/ml) revealed that all of the inhibitors induced the
      formation of apoC-II dimers enriched in alpha-helical content while the
      activators promoted the formation of stable apoC-II tetramers with increased beta
      structure. Kinetic analysis identified modulators of apoC-II fibril formation
      that were effective at concentrations as low as 10 MUM, corresponding to a
      modulator-to-apoC-II ratio of approximately 1:10. Delayed addition of the test
      compounds after fibril formation had commenced allowed the effects of selected
      amphiphiles on fibril elongation to be determined separately from their effects
      on fibril nucleation. The results indicated that specific amphiphiles induce
      structural changes in apoC-II that cause separate and independent effects on
      fibril nucleation and elongation. Low-molecular-weight amphipathic lipids and
      detergents may serve as useful, stage-specific modulators of protein self
      assembly and fibril formation in disease-prevention strategies.

PMID- 21185303
TI  - Derepression of bacterial transcription-repair coupling factor is associated with
      a profound conformational change.
AB  - Transcription-repair coupling factor (TRCF; the product of the mfd gene) is a
      widely conserved bacterial protein that couples DNA repair with transcription.
      TRCF recognizes RNA polymerase stalled at a noncoding lesion in the DNA template
      strand, uses the energy from ATP hydrolysis to disrupt the transcription complex,
      and stimulates DNA repair by recruiting UvrA, a component of the nucleotide
      excision repair machinery, to the site. TRCF is a large (130 kDa) multifunctional
      protein with a complex structure-function relationship consisting of a compact
      arrangement of eight structured domains linked by flexible linkers. Through a
      conserved, intramolecular, interdomain interaction, TRCF is held in a
      conformation in which its enzymatic activities (ATPase activity and DNA
      translocase activity) are strongly repressed. Disruption of the repressive
      interdomain interaction by amino acid substitutions within the interface
      derepresses ATPase and DNA translocase activities. In this work, we have shown
      that derepressed TRCF mutants are dramatically sensitized to limited proteolysis
      compared with repressed TRCF, pointing to an altered conformational state.
      Analysis of the protease cleavage sites mapped onto the structure of the
      repressed TRCF conformation indicates that (1) the cleavage sites tend to cluster
      at linkers connecting the TRCF structured domains, and (2) many of the cleavage
      sites sensitized in the derepressed TRCF are partially or completely buried to
      protease access in the repressed TRCF structure. We conclude that TRCF
      derepression is associated with profound conformational changes that primarily
      involve a reorganization of the interdomain interactions.

PMID- 21185304
TI  - Nucleotide pocket thermodynamics measured by EPR reveal how energy partitioning
      relates myosin speed to efficiency.
AB  - We have used spin-labeled ADP to investigate the dynamics of the nucleotide
      binding pocket in a series of myosins, which have a range of velocities. Electron
      paramagnetic resonance spectroscopy reveals that the pocket is in equilibrium
      between open and closed conformations. In the absence of actin, the closed
      conformation is favored. When myosin binds actin, the open conformation becomes
      more favored, facilitating nucleotide release. We found that faster myosins favor
      a more closed pocket in the actomyosin*ADP state, with smaller values of
      DeltaH(0) and DeltaS(0), even though these myosins release ADP at a faster rate.
      A model involving a partitioning of free energy between work-generating steps
      prior to rate-limiting ADP release explains both the unexpected correlation
      between velocity and opening of the pocket and the observation that fast myosins
      are less efficient than slow myosins.

PMID- 21185305
TI  - Structural and functional studies of fatty acyl adenylate ligases from E. coli
      and L. pneumophila.
AB  - Fatty acyl-AMP ligase (FAAL) is a new member of a family of adenylate-forming
      enzymes that were recently discovered in Mycobacterium tuberculosis. They are
      similar in sequence to fatty acyl-coenzyme A (CoA) ligases (FACLs). However,
      while FACLs perform a two-step catalytic reaction, AMP ligation followed by CoA
      ligation using ATP and CoA as cofactors, FAALs produce only the acyl adenylate
      and are unable to perform the second step. We report X-ray crystal structures of
      full-length FAAL from Escherichia coli (EcFAAL) and FAAL from Legionella
      pneumophila (LpFAAL) bound to acyl adenylate, determined at resolution limits of
      3.0 and 1.85 A, respectively. The structures share a larger N-terminal domain and
      a smaller C-terminal domain, which together resemble the previously determined
      structures of FAAL and FACL proteins. Our two structures occur in quite different
      conformations. EcFAAL adopts the adenylate-forming conformation typical of FACLs,
      whereas LpFAAL exhibits a unique intermediate conformation. Both EcFAAL and
      LpFAAL have insertion motifs that distinguish them from the FACLs. Structures of
      EcFAAL and LpFAAL reveal detailed interactions between this insertion motif and
      the interdomain hinge region and with the C-terminal domain. We suggest that the
      insertion motifs support sufficient interdomain motions to allow substrate
      binding and product release during acyl adenylate formation, but they preclude
      CoA binding, thereby preventing CoA ligation.

PMID- 21185306
TI  - Construction of a genetic multiplexer to toggle between chemosensory pathways in
      Escherichia coli.
AB  - Many applications require cells to switch between discrete phenotypic states.
      Here, we harness the FimBE inversion switch to flip a promoter, allowing
      expression to be toggled between two genes oriented in opposite directions. The
      response characteristics of the switch are characterized using two-color
      cytometry. This switch is used to toggle between orthogonal chemosensory pathways
      by controlling the expression of CheW and CheW*, which interact with the Tar
      (aspartate) and Tsr* (serine) chemoreceptors, respectively. CheW* and Tsr* each
      contain a mutation at their protein-protein interface such that they interact
      with each other. The complete genetic program containing an arabinose-inducible
      FimE controlling CheW/CheW* (and constitutively expressed tar/tsr*) is
      transformed into an Escherichia coli strain lacking all native chemoreceptors.
      This program enables bacteria to swim toward serine or aspartate in the absence
      or in the presence of arabinose, respectively. Thus, the program functions as a
      multiplexer with arabinose as the selector. This demonstrates the ability of
      synthetic genetic circuits to connect to a natural signaling network to switch
      between phenotypes.

PMID- 21185307
TI  - Tracing the detail: how mutations affect binding modes and thermodynamic
      signatures of closely related aldose reductase inhibitors.
AB  - Improvements on the computational methods for affinity prediction from the
      structure of protein-ligand complexes require a better understanding of the
      nature of molecular interactions and biomolecular recognition principles. In the
      present contribution, the binding of two chemically closely related human aldose
      reductase inhibitors had been studied by high-resolution X-ray analysis (0.92
      1.35 A) and isothermal titration calorimetry against a series of single-site
      mutants of the wild-type protein. A crucial threonine thought to be involved in a
      short bromine-to-oxygen halogen bond to the inhibitors in the wild type has been
      mutated to the structurally similar residues alanine, cysteine, serine and
      valine. Overall, structurally, the binding mode of the inhibitors is conserved;
      however, small but significant geometrical adaptations are observed as a
      consequence of the spatial and electronic changes at the mutation site. They
      involve the opening of a central bond angle and shifts in consequence of the lost
      or gained halogen bonds. Remarkably, the tiny structural changes are responded by
      partly strong modulation of the thermodynamic profiles. Even though the free
      energy of binding is maximally perturbed by only 7 kJ/mol, much stronger
      modulations and shifts in the enthalpy and entropy signatures are revealed, which
      indicate a pronounced enthalpy/entropy compensation. However, an explanatory
      correlation can be detected when facing these perturbances against the small
      structural changes. This also provides deeper insights into how single-site
      mutations can alter the selectivity profile of closely related ligands against a
      target protein.

PMID- 21185308
TI  - Structural studies of ROK fructokinase YdhR from Bacillus subtilis: insights into
      substrate binding and fructose specificity.
AB  - The main pathway of bacterial sugar phosphorylation utilizes specific
      phosphoenolpyruvate phosphotransferase system (PTS) enzymes. In addition to the
      classic PTS system, a PTS-independent secondary system has been described in
      which nucleotide-dependent sugar kinases are used for monosaccharide
      phosphorylation. Fructokinase (FK), which phosphorylates d-fructose with ATP as a
      cofactor, has been shown to be a member of this secondary system. Bioinformatic
      analysis has shown that FK is a member of the "ROK" (bacterial Repressors,
      uncharacterized Open reading frames, and sugar Kinases) sequence family. In this
      study, we report the crystal structures of ROK FK from Bacillus subtilis (YdhR)
      (a) apo and in the presence of (b) ADP and (c) ADP/d-fructose. All structures
      show that YdhR is a homodimer with a monomer composed of two similar alpha/beta
      domains forming a large cleft between domains that bind ADP and D-fructose.
      Enzymatic activity assays support YdhR function as an ATP-dependent fructose
      kinase.

PMID- 21185309
TI  - Ubiquitin is a novel substrate for human insulin-degrading enzyme.
AB  - Insulin-degrading enzyme (IDE) can degrade insulin and amyloid-beta, peptides
      involved in diabetes and Alzheimer's disease, respectively. IDE selects its
      substrates based on size, charge, and flexibility. From these criteria, we
      predict that IDE can cleave and inactivate ubiquitin (Ub). Here, we show that IDE
      cleaves Ub in a biphasic manner, first, by rapidly removing the two C-terminal
      glycines (k(cat)=2 s(-1)) followed by a slow cleavage between residues 72 and 73
      (k(cat)=0.07 s(-1)), thereby producing the inactive 1-74 fragment of Ub (Ub1-74)
      and 1-72 fragment of Ub (Ub1-72). IDE is a ubiquitously expressed cytosolic
      protein, where monomeric Ub is also present. Thus, Ub degradation by IDE should
      be regulated. IDE is known to bind the cytoplasmic intermediate filament protein
      nestin with high affinity. We found that nestin potently inhibits the cleavage of
      Ub by IDE. In addition, Ub1-72 has a markedly increased affinity for IDE (~90
      fold). Thus, the association of IDE with cellular regulators and product
      inhibition by Ub1-72 can prevent inadvertent proteolysis of cellular Ub by IDE.
      Ub is a highly stable protein. However, IDE instead prefers to degrade peptides
      with high intrinsic flexibility. Indeed, we demonstrate that IDE is exquisitely
      sensitive to Ub stability. Mutations that only mildly destabilize Ub
      (DeltaDeltaG<0.6 kcal/mol) render IDE hypersensitive to Ub with rate enhancements
      greater than 12-fold. The Ub-bound IDE structure and IDE mutants reveal that the
      interaction of the exosite with the N-terminus of Ub guides the unfolding of Ub,
      allowing its sequential cleavages. Together, our studies link the control of Ub
      clearance with IDE.

PMID- 21185310
TI  - Crystal structures of Enoyl-ACP reductases I (FabI) and III (FabL) from B.
      subtilis.
AB  - Enoyl-[acyl carrier protein] (ACP) reductase (ENR) is a key enzyme in type II
      fatty acid synthesis that catalyzes the last step in each elongation cycle.
      Therefore, it has been considered as a target for antibiotics. However, recent
      studies indicate that some pathogens have more than one ENR; in particular,
      Bacillus subtilis has two ENRs, FabI and FabL. The crystal structures of the
      ternary complexes of BsFaBI and BsFabL are found as a homotetramer showing the
      same overall structure despite a sequence identity of only 24%. The positions of
      the catalytic dyad of Tyr-(Xaa)(6)-Lys in FabL are almost identical to that of
      FabI, but a detailed structural analysis shows that FabL shares more structural
      similarities with FabG and other members of the SDR (short-chain alcohol
      dehydrogenase/reductase) family. The apo FabL structure shows significantly
      different conformations at the cofactor and the substrate-binding regions, and
      this resulted in a totally different tetrameric arrangement reflecting the
      flexibility of these regions in the absence of the cofactor and
      substrate/inhibitor.

PMID- 21185311
TI  - Spontaneous proton transfer to a conserved intein residue determines on-pathway
      protein splicing.
AB  - The discovery of inteins, which are protein-splicing elements, has stimulated
      interest for various applications in chemical biology, bioseparations, drug
      delivery, and sensor development. However, for inteins to effectively contribute
      to these applications, an increased mechanistic understanding of cleavage and
      splicing reactions is required. While the multistep chemical reaction that leads
      to splicing is often explored and utilized, it is not clear how the intein
      navigates through the reaction space. The sequence of reaction steps must
      progress in concert in order to yield efficient splicing while minimizing off
      pathway cleavage reactions. In this study, we demonstrate that formation of a
      previously identified branched intermediate is the critical step for determining
      splicing over cleavage products. By combining experimental assays and quantum
      mechanical simulations, we identify the electrostatic interactions that are
      important to the dynamics of the reaction steps. We illustrate, via an animated
      simulation trajectory, a proton transfer from the first C-terminal extein residue
      to a conserved aspartate, which synchronizes the multistep enzymatic reaction
      that is key to splicing. This work provides new insights into the complex
      interplay between critical active-site residues in the protein splicing
      mechanism, thereby facilitating biotechnological application while shedding light
      on multistep enzyme activity.

PMID- 21185312
TI  - Genetic incorporation of a photo-crosslinkable amino acid reveals novel protein
      complexes with GRB2 in mammalian cells.
AB  - Cell signaling pathways are essentially organized through the distribution of
      various types of binding domains in signaling proteins, with each domain binding
      to specific target molecules. Although identification of these targets is crucial
      for mapping the pathways, affinity-based or copurification methods are
      insufficient to distinguish between direct and indirect interactions in a
      cellular context. In the present study, we developed another approach involving
      the genetic encoding of a photo-crosslinkable amino acid. p-Trifluoromethyl
      diazirinyl-l-phenylalanine was thus incorporated at a defined site in the Src
      homology 2 (SH2) domain of the adaptor protein GRB2 in human embryonic kidney
      cells. These cells were exposed to 365-nm light after an epidermal growth factor
      stimulus, and the crosslinkable GRB2-SH2 domain exclusively formed covalent bonds
      with directly interacting proteins. Proteomic mass spectrometry analysis
      identified these direct binders of GRB2-SH2 separately from the proteins
      noncovalently bound to the Src homology 3 domains of GRB2. In addition to two
      signaling-associated proteins (GIT1 and AF6), the heterogeneous nuclear
      ribonucleoproteins F, H1, and H2 were thus identified as novel direct binders.
      The results revealed a connection between the cell signaling protein and the
      nuclear machinery involved in mRNA processing, and demonstrated the usefulness of
      genetically encoded photo-crosslinkers for mapping protein-protein interactions
      in cells.

PMID- 21185313
TI  - The effects of huperzine A and IDRA 21 on visual recognition memory in young
      macaques.
AB  - Nootropic agents or cognitive enhancers are purported to improve mental functions
      such as cognition, memory, or attention. The aim of our study was to determine
      the effects of two possible cognitive enhancers, huperzine A and IDRA 21, in
      normal young adult monkeys performing a visual memory task of varying degrees of
      difficulty. Huperzine A is a reversible acetylcholinesterase (AChE) inhibitor,
      its administration results in regionally specific increases in acetylcholine
      levels in the brain. In human clinical trials, Huperzine A resulted in cognitive
      improvement in patients with mild to moderate form of Alzheimer's disease (AD)
      showing its potential as a palliative agent in the treatment of AD. IDRA 21 is a
      positive allosteric modulator of glutamate AMPA receptors. It increases
      excitatory synaptic strength by attenuating rapid desensitization of AMPA
      receptors and may thus have beneficial therapeutic effects to ameliorate memory
      deficits in patients with cognitive impairments, including AD. The present study
      evaluated the effects of the two drugs in normal, intact, young adult monkeys to
      determine whether they can result in cognitive enhancement in a system that is
      presumably functioning optimally. Six young pigtail macaques (Macaca nemestrina)
      were trained on delayed non-matching-to-sample task, a measure of visual
      recognition memory, up to criterion of 90% correct responses on each of the four
      delays (10s, 30s, 60s, and 90s). They were then tested on two versions of the
      task: Task 1 included the four delays intermixed within a session and the monkeys
      performed it with the accuracy of 90%. Task 2 included, in each of 24 trials, a
      list of six objects presented in succession. Two objects from the list were then
      presented for choice paired with novel objects and following two of the four
      delays intermixed within a session. This task with a higher mnemonic demand
      yielded an average performance of 64% correct. Oral administration of huperzine A
      did not significantly affect the monkeys' performance on either task. However, a
      significant negative correlation was found between the baseline performance on
      each delay and the change in performance under huperzine A, suggesting that under
      conditions in which the subjects were performing poorly (55-69%), the drug
      resulted in improved performance, whereas no improvement was obtained when the
      baseline was close to 90%. In fact, when the subjects were performing very well,
      huperzine A tended to reduce the performance accuracy, indicating that in a
      system that functions optimally, the increased availability of acetylcholine does
      not improve performance or memory, especially when the animals are close to the
      maximum performance. In contrast, oral administration of IDRA 21 significantly
      improved performance on Task 2, especially on the longest delay. This finding
      supports the potential use of this drug in treatment of cognitive and memory
      disorders. This article is part of a Special Issue entitled 'Trends in
      neuropharmacology: in memory of Erminio Costa'.

PMID- 21185314
TI  - Short- and long-term depression at glutamatergic synapses on hippocampal
      interneurons by group I mGluR activation.
AB  - Group I metabotropic glutamate receptors (mGluRs) are expressed by many
      interneurons of the hippocampus. Although they have been implicated in short- and
      long-term synaptic plasticity of glutamatergic transmission, their roles in
      modulating transmission to interneurons are incompletely understood. The
      selective group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) acutely
      depressed transmission at synapses in the feed-forward inhibitory pathway made by
      Schaffer collaterals on interneurons in the rat hippocampal CA1 sub-field. DHPG
      elicited a qualitatively similar depression at synapses made by pyramidal neuron
      axon collaterals on interneurons in the feedback circuit in stratum oriens.
      Selective blockers revealed a link from mGluR1 to reversible, and mGluR5 to long
      lasting, depression. The acute DHPG-induced depression was consistently
      accompanied by an elevation in paired-pulse ratio, implying a presynaptic
      decrease in release probability. However, it was also attenuated by blocking G
      protein and Ca(2+) signalling within the postsynaptic neuron, arguing for a
      retrograde signalling cascade. The DHPG-evoked depression was unaffected by
      antagonists of CB1 and GABA(B) receptors but was occluded when presynaptic P/Q
      type Ca(2+) channels were blocked. Finally, high-frequency stimulation delivered
      to an independent conditioning pathway evoked a heterosynaptic reversible
      depression, which was sensitive to group I mGluR antagonists. Group I mGluRs thus
      powerfully modulate synaptic excitation of hippocampal interneurons and mediate
      inter-synaptic cross-talk. This article is part of a Special Issue entitled
      'Synaptic Plasticity & Interneurons'.

PMID- 21185315
TI  - A systems genetic analysis of alcohol drinking by mice, rats and men: influence
      of brain GABAergic transmission.
AB  - Genetic influences on the predisposition to complex behavioral or physiological
      traits can reflect genetic polymorphisms that lead to altered gene product
      function, and/or variations in gene expression levels. We have explored
      quantitative variations in an animal's alcohol consumption, using a genetical
      genomic/phenomic approach. In our studies, gene expression is correlated with
      amount of alcohol consumed, and genomic regions that regulate the alcohol
      consumption behavior and the quantitative levels of gene expression (behavioral
      and expression quantitative trait loci [QTL]) are determined and used as a filter
      to identify candidate genes predisposing the behavior. We determined QTLs for
      alcohol consumption using the LXS panel of recombinant inbred mice. We then
      identified genes that were: 1) differentially expressed between five high and
      five low alcohol-consuming lines or strains of mice; and 2) were physically
      located in, or had an expression QTL (eQTL) within the alcohol consumption QTLs.
      Comparison of mRNA and protein levels in brains of high and low alcohol consuming
      mice led us to a bioinformatic examination of potential regulation by microRNAs
      of an identified candidate transcript, Gnb1 (G protein beta subunit 1). We
      combined our current analysis with our earlier work identifying candidate genes
      for the alcohol consumption trait in mice, rats and humans. Our overall analysis
      leads us to postulate that the activity of the GABAergic system, and in
      particular GABA release and GABA receptor trafficking and signaling, which
      involves G protein function, contributes significantly to genetic variation in
      the predisposition to varying levels of alcohol consumption. This article is part
      of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio
      Costa'.

PMID- 21185316
TI  - Restraint stress-induced reduction in prepulse inhibition in Brown Norway rats:
      role of the CRF2 receptor.
AB  - Stress plays a role in many psychiatric disorders that are characterized by
      deficits in prepulse inhibition (PPI), a form of sensorimotor gating.
      Corticotropin-releasing factor (CRF) is one of the most important
      neurotransmitters involved in behavioral components of the stress response.
      Central infusion of CRF reduces PPI in both rats and mice. In mice, it has been
      shown that CRF(1) receptor activation mediates the effect of exogenous CRF on
      PPI. However, the roles of the two CRF receptors in a stress-induced reduction in
      PPI are not known. We sought to determine whether CRF(1) and/or CRF(2) receptor
      blockade attenuates a stress-induced reduction of PPI in rats. In separate
      experiments, we assessed PPI in Brown Norway rats after exposure to 5 days of 2-h
      restraint, and after pretreatment with the CRF(1) receptor antagonist, CP-154,526
      (20.0 mg/kg), or the CRF(2) receptor antagonist, antisauvagine-30 (10.0 MUg).
      Repeated, but not acute, restraint decreased PPI and attenuated the increase in
      PPI caused by repeated PPI testing. Blockade of the CRF(1) receptor did not
      attenuate the effect of repeated restraint on PPI or grooming behavior. While
      CRF(2) receptor blockade did attenuate the effect of repeated restraint on PPI,
      repeated ICV infusion of the selective CRF(2) receptor agonist urocortin III, did
      not affect PPI. These findings demonstrate the effect of stress on sensorimotor
      gating and suggest that the CRF(2) receptor mediates this effect in rats.

PMID- 21185318
TI  - A microdialysis study of ST1936, a novel 5-HT6 receptor agonist.
AB  - The function of 5-HT6 receptors, one of the last additions to the large family of
      5-HT receptors, is largely unknown due to the limited knowledge of their
      transduction mechanisms, lack of full centrally acting agonists and
      inconsistencies in the pharmacological and neurochemical effects of the
      antagonists. Recently, a new full agonist, ST1936, with nanomolar affinity for 5
      HT6 receptors, has become available. Here we report the effect of ST1936 (5-10-20
      mg/kg/ip) on dialysate DA, NA and 5-HT in the medial prefrontal cortex (PFCX) and
      in the shell and core of the nucleus accumbens (NAc). Systemic administration of
      ST1936 dose-dependently increased dialysate DA and NA in the NAc shell and PFCX
      and to a lesser extent in the NAc core; these effects were prevented by systemic
      administration of the two 5-HT6 receptor antagonists, SB271046 (10-20 mg/kg/ip)
      and SB399885 (5 mg/kg/ip). These properties of ST1936 suggest that 5-HT6
      receptors control the activity of DA and NA neurons projecting to the NAc and to
      the PFCX.

PMID- 21185317
TI  - Synaptic plasticity in inhibitory neurons of the auditory brainstem.
AB  - There is a growing appreciation of synaptic plasticity in the early levels of
      auditory processing, and particularly of its role in inhibitory circuits.
      Synaptic strength in auditory brainstem and midbrain is sensitive to standard
      protocols for induction of long-term depression, potentiation, and spike-timing
      dependent plasticity. Differential forms of plasticity are operative at synapses
      onto inhibitory versus excitatory neurons within a circuit, and together these
      could serve to tune circuits involved in sound localization or multisensory
      integration. Such activity-dependent control of synaptic function in inhibitory
      neurons may also be expressed after hearing loss and could underlie persistent
      neuronal activity in patients with tinnitus. This article is part of a Special
      Issue entitled 'Synaptic Plasticity & Interneurons'.

PMID- 21185319
TI  - LTP and LTD in cortical GABAergic interneurons: emerging rules and roles.
AB  - Recent studies of excitatory transmission in cortical interneurons reveal a
      surprising diversity of forms of long-term plasticity. LTP and LTD can be
      elicited at many synapses on interneurons, and pharmacological manipulations
      implicate NMDA, calcium-permeable AMPA and metabotropic receptors in the
      induction of plasticity. Distinct patterns are beginning to emerge in identified
      pathways, as defined by the cells of origin of the presynaptic glutamatergic
      axons and the postsynaptic interneuron subtypes. We review this literature, and
      speculate about the possible adaptive significance of long-term activity
      dependent changes in transmission for cortical information processing. This
      article is part of a Special Issue entitled 'Synaptic Plasticity & Interneurons'.

PMID- 21185320
TI  - What goes through the gate? Exploring interference with visual feature binding.
AB  - A series of experiments explored the mechanisms determining the encoding and
      storage of features and objects in visual working memory. We contrasted the
      effects of three types of visual suffix on cued recall of a display of colored
      shapes. The suffix was presented after the display and before the recall cue. The
      latter was either the color or shape of one of the objects and signaled recall of
      the object's other feature. In Experiments 1 and 2, we found a larger effect of
      'plausible' suffixes comprising features (color and shape) drawn from the
      experimental set, relative to the effect of 'implausible' suffixes comprising
      features outside the experimental set. Experiment 3 extended this pattern by
      showing that 'semi-plausible' suffixes containing only one feature (either color
      or shape) from the experimental set had an equivalent effect to those with both
      features from the set. Reduction in accuracy was mainly due to an increase in
      recall of suffix features, rather than within-display confusions. The findings
      suggest a feature-based filtering process in visual working memory, with any
      stimuli that pass through this filter serving to directly overwrite existing
      object representations.

PMID- 21185321
TI  - Interactions between attention and visual short-term memory (VSTM): what can be
      learnt from individual and developmental differences?
AB  - An ever increasing amount of research in the fields of developmental psychology
      and adult cognitive neuroscience explores attentional control as a driver of
      visual short-term and working memory capacity limits ("VSTM" and "VWM",
      respectively). However, these literatures have thus far been disparate: they use
      different measures or different labels, and the constructs of interest often
      appear to be quite distinct. In the current review, we attempt to bridge these
      gaps across disciplines and explore the extent to which these two literatures
      might support one another. In order to do this, we explore five principal
      questions of interest to members of both communities: (1) To what extent are
      measures of VSTM, VWM and attentional control commensurate across the
      developmental and adult literatures? (2) To what extent do individual differences
      in attentional control account for why some children, just like some adults, show
      poorer VSTM and VWM capacity than others? (3) Can developmental improvements in
      VSTM and VWM capacity also be explained by differences in attentional control?
      (4) What novel insights can be gained by studying the developmental cognitive
      neuroscience of attention and VSTM and VWM? (5) Can visual short-term and working
      memory capacity be modulated by training and, if so, how can training effects
      inform the relationships between attention and VSTM? Throughout, we evaluate the
      central thesis that variability in attentional control, both between individuals
      and over development, is a driver of variability in VSTM and VWM capacity.

PMID- 21185322
TI  - Rats' learned preferences for flavors encountered early or late in a meal paired
      with the postingestive effects of glucose.
AB  - Rats learn to prefer flavors that are followed by postingestive effects of
      nutrients. This experiment investigated whether the timing of a flavor
      (specifically, in the first or second half of the meal) influences learning about
      that flavor. Stronger learning about earlier or later flavors would indicate when
      the rewarding postingestive effects of nutrients are sensed. Rats with
      intragastric (IG) catheters drank saccharin-sweetened, calorically-dilute
      solutions with distinct flavors added, accompanied by IG infusion of glucose
      (+sessions) or water (-sessions). In both types of sessions, an "Early" flavor
      was provided for the first 8 min and a "Late" flavor for the last 8 min. Thus,
      rats were trained with Early(+) and Late(+) in high-calorie meals, and Early(-)
      and Late(-) in low-calorie meals. Strength of the learned preference for Early(+)
      and Late(+) was then assessed in a series of two-bottle choice tests between
      Early(+) vs. Early(-), Late(+) vs. Late(-), Early(+) vs. Late(+), and Early(-)
      vs. Late(-). Rats preferred both Early(+) and Late(+) over the respective (-)
      flavors. But Early(+) was only preferred when rats were tested hungry. Late(+)
      was preferred when rats were tested hungry or recently satiated. This indicates
      qualitatively different associations learned about flavors at different points in
      the meal. While not supporting the idea that postingestive effects become most
      strongly associated with later-occurring ("dessert") flavors, it does suggest a
      reason dessert flavors may remain attractive in the absence of hunger.

PMID- 21185323
TI  - The number of equilibria in the diallelic Levene model with multiple demes.
AB  - The Levene model is the simplest mathematical model to describe the evolution of
      gene frequencies in spatially subdivided populations. It provides insight into
      how locally varying selection promotes a population's genetic diversity. Despite
      its simplicity, interesting problems have remained unsolved even in the diallelic
      case. In this paper we answer an open problem by establishing that for two
      alleles at one locus and J demes, up to 2J-1 polymorphic equilibria may coexist.
      We first present a proof for the case of stable monomorphisms and then show that
      the result also holds for protected alleles. These findings allow us to prove
      that any odd number (up to 2J-1) of equilibria is possible, before we extend the
      proof to even numbers. We conclude with some numerical results and show that for
      J>2, the proportion of parameter space affording this maximum is extremely small.

PMID- 21185324
TI  - cDNA cloning, structural, and functional analyses of venom phospholipases A2 and
      a Kunitz-type protease inhibitor from steppe viper Vipera ursinii renardi.
AB  - Snake venom phospholipases A2 (PLA2s) display a wide array of biological
      activities and are each characteristic to the venom. Here, we report on the cDNA
      cloning and characterization of PLA2s from the steppe viper Vipera ursinii
      renardi venom glands. Among the five distinct PLA2 cDNAs cloned and sequenced,
      the most common were the clones encoding a basic Ser-49 containing PLA2 (Vur
      S49). Other clones encoded either ammodytin analogs I1, I2d and I2a (designated
      as Vur-PL1, Vur-PL2 and Vur-PL3, respectively) or an ammodytoxin-like PLA2
      (Vurtoxin). Additionally, a novel Kunitz-type trypsin inhibitor for this venom
      species was cloned and sequenced. Comparison of these PLA2 and Kunitz inhibitor
      sequences with those in the sequence data banks suggests that the viper V. u.
      renardi is closely related to Vipera ammodytes and Vipera aspis. Separation of V.
      u. renardi venom components by gel-filtration and ion-exchange chromatography
      showed the presence of many PLA2 isoforms. Remarkably, the most abundant PLA2
      isolated was Vur-PL2 while Vur-S49 analog was in very low yield. There are great
      differences between the proportion of cDNA clones and that of the proteins
      isolated. Two Vur-PL2 isoforms (designated as Vur-PL2A and Vur-PL2B)
      indistinguishable by masses, peptide mass fingerprinting, N-terminal sequences
      and CD spectroscopy were purified from the pooled venom. However, when
      rechromatographed on cation-exchanger, Vur-PL2A showed only one peak
      corresponding to Vur-PL2B, suggesting the existence of conformers for Vur-PL2.
      Vur-PL2B was weakly cytotoxic to rat pheochromocytoma PC12 cells and showed both
      strong anticoagulant and anti-platelet activities. This is the first case of a
      strong anticoagulating ammodytin I analog in Vipera venom.

PMID- 21185325
TI  - Modification of collagen with a natural cross-linker, procyanidin.
AB  - We have investigated the modification of collagen with a natural plant
      polyphenol, procyanidin under acidic conditions. Fourier transform infrared
      spectroscopy (FTIR) and Atomic force microscopy (AFM) studies demonstrate that
      the hydrogen bond interactions between collagen and procyanidin does not destroy
      the triple helix conformation of collagen, and the fibril aggregation occurs
      because of the cross-linking with procyanidin. The water contact angle (WCA)
      tests indicate that the hydrophobicity of the procyanidin modified collagen films
      can be improved. Whereas, the water vapor permeability (WVP) of the films
      decrease with the increasing procyanidin content due to the formation of denser
      structure. Moreover, differential scanning calorimetry (DSC) and
      thermogravimetric (TG) measurements reveal that the collagen/procyanidin films
      have improved thermal stability in comparison with pure collagen. The present
      study reveals that procyanidin stabilizes collagen as a cross-linker and
      preserves its triple helical structure.

PMID- 21185326
TI  - N15: the linear phage-plasmid.
AB  - The lambdoid phage N15 of Escherichia coli is very unusual among temperate phages
      in that its prophage is not integrated into chromosome but is a linear plasmid
      molecule with covalently closed ends. Upon infection the phage DNA circularises
      via cohesive ends, then phage-encoded enzyme, protelomerase, cuts at an inverted
      repeat site and forms hairpin ends (telomeres) of the linear plasmid prophage.
      Replication of the N15 prophage is initiated at an internally located ori site
      and proceeds bidirectionally resulting in formation of duplicated telomeres. Then
      the N15 protelomerase cuts duplicated telomeres generating two linear plasmid
      molecules with hairpin telomeres. Stable inheritance of the plasmid prophage is
      ensured by partitioning operon similar to the F factor sop operon. Unlike F sop,
      the N15 centromere consists of four inverted repeats dispersed in the genome. The
      multiplicity and dispersion of centromeres are required for efficient
      partitioning of a linear plasmid. The centromeres are located in N15 genome
      regions involved in phage replication and control of lysogeny, and binding of
      partition proteins at these sites regulates these processes. Two N15-related
      lambdoid Siphoviridae phages, phiKO2 in Klebsiella oxytoca and pY54 in Yersinia
      enterocolitica, also lysogenize their hosts as linear plasmids, as well as
      Myoviridae marine phages VP882 and VP58.5 in Vibrio parahaemolyticus and PhiHAP-1
      in Halomonas aquamarina. The genomes of all these phages contain similar
      protelomerase genes, lysogeny modules and replication genes, as well as plasmid
      partitioning genes, suggesting that these phages may belong to a group diverged
      from a common ancestor.

PMID- 21185327
TI  - Acute exposure to tributyltin induces c-fos activation in the hypothalamic
      arcuate nucleus of adult male mice.
AB  - Tributyltin (TBT) is a largely diffused environmental pollutant, banned from
      paints in the European Union from 2003. However, the level of TBT (and other
      organotins) in food, particularly fish and shellfish, remains still high. Several
      studies demonstrated that TBT is involved in the development of obesity, via
      peripheral action, but currently, there are only a few data illustrating effects
      of TBT on the nervous system. In the present study, we tested the hypothesis that
      acute exposure to TBT may directly activate brain cells in particular, in those
      hypothalamic nuclei regulating the food intake. To this purpose, TBT was orally
      administered at a single dose (10 mg/kg/body weight) to two groups of adult male
      mice: regularly fed or fasted for 24 h. Mice were sacrificed 90 min after the TBT
      administration and perfused by 4% paraformaldehyde. Brains were quickly
      dissected, frozen and sectioned for immunocytochemical detection of c-fos, a
      common marker of cell activation. In both, fed or fasted mice, exposure to TBT
      induced a significant increase of c-fos expression in the arcuate nucleus in
      comparison to control mice. The other nuclei involved in the control of feeding
      behavior did not show any significant increase. These data are the first in vivo
      demonstration that TBT has not only peripheral effects, but also may activate
      elements in the brain, in particular in a crucial region for the regulation of
      food intake like the arcuate nucleus.

PMID- 21185328
TI  - Ramsay-Hunt syndrome.

PMID- 21185329
TI  - Results of total DNA measurement in koi tissue by Koi Herpes Virus real-time PCR.
AB  - Koi Herpes Virus (KHV) has been classified recently as a member of the
      Alloherpesviridae within the Herpesvirales order (Waltzek et al., 2005). Although
      one of the unique features of Herpesviridae, the sister family of Herpesvirales,
      is latent infection, it has not been demonstrated consistently that KHV of
      Alloherpesviridae can cause latent infection and be reactivated from latency. To
      investigate if KHV genomic DNA is present in koi exposed to KHV infection, 10
      healthy fish were investigated from a koi population with a history of a KHV
      outbreak. No gross lesions or microscopic changes were observed at necropsy or by
      histological examination. No infectious virus was isolated from either the blood
      plasma or tissues. However, KHV DNA was detected in the white blood cells of nine
      of the ten fish by real-time PCR and PCR-Southern blot. KHV DNA was also detected
      in the brain, eye, spleen, gills hematopoietic kidney, trunk kidney, and
      intestine of nine of the ten fish by PCR-Southern blot. Interestingly, KHV DNA
      was also detected in the intestinal contents from seven of ten koi. Portions of
      major capsid gene DNA, amplified from two of the ten koi WBCs, were found to be
      identical to KHV-U. This study demonstrated that KHV genomic DNA can be detected
      in normal koi exposed previously to KHV and suggests that KHV becomes latent in
      fish.

PMID- 21185330
TI  - Establishment and validation of an ELISA for the quantitation of HBsAg in
      recombinant hepatitis B vaccines.
AB  - Commercial enzyme-linked immunosorbent assay (ELISA) kits for the determination
      of the in vitro potency of recombinant hepatitis B vaccines, which detect
      hepatitis B surface antigen (HBsAg), have been used frequently as an alternative
      for traditional in vivo potency tests. With the constant need for validation
      procedures, an ELISA that could be employed to determine the in vitro potency of
      five recombinant hepatitis B vaccines simultaneously was established using two
      monoclonal antibodies. The use of two monoclonal antibodies produced "in house"
      specific for the small envelope protein S of the hepatitis B virus (HBV) resulted
      in the production of a highly specific, sensitive and stable ELISA. The standard
      ELISA parameters used in this study, considering the HBsAg content of each
      recombinant hepatitis B vaccine evaluated, resulted in a standard curve that
      could be applied for potency evaluations of different, commercial hepatitis B
      vaccine lots.

PMID- 21185331
TI  - Increased sensitivity for various rotavirus genotypes in stool specimens by
      amending three mismatched nucleotides in the forward primer of a real-time RT-PCR
      assay.
AB  - The real-time TaqMan RT-PCR assay (Pang et al., 2004) did not detect 14 clinical
      samples with rotavirus G2 genotype. Three to five nucleotides (nt) were found to
      be mismatched between the published forward primer when compared to G2P[4],
      G2P[8], G3P[4], G9P[4], G8 and G12 sequences. An additional forward primer was
      designed and included in a modified assay to test the 14 clinical samples and 12
      samples with known rotavirus G and P genotypes. The modified assay has improved
      significantly the sensitivity for specific rotavirus strains without affecting
      the detection of other genotypes, creating a molecular assay with broad detection
      of various genotypes of group A rotaviruses.

PMID- 21185332
TI  - Anthracene-based inhibitors of dengue virus NS2B-NS3 protease.
AB  - Dengue virus (DENV) is a mosquito-borne flavivirus that has strained global
      healthcare systems throughout tropical and subtropical regions of the world. In
      addition to plaguing developing nations, it has re-emerged in several developed
      countries with recent outbreaks in the USA (CDC, 2010), Australia (Hanna et al.,
      2009), Taiwan (Kuan et al., 2010) and France (La Ruche et al., 2010). DENV
      infection can cause significant disease, including dengue fever, dengue
      hemorrhagic fever, dengue shock syndrome, and death. There are no approved
      vaccines or antiviral therapies to prevent or treat dengue-related illnesses.
      However, the viral NS2B-NS3 protease complex provides a strategic target for
      antiviral drug development since NS3 protease activity is required for virus
      replication. Recently, we reported two compounds with inhibitory activity against
      the DENV protease in vitro and antiviral activity against dengue 2 (DEN2V) in
      cell culture (Tomlinson et al., 2009a). Analogs of one of the lead compounds were
      purchased, tested in protease inhibition assays, and the data evaluated with
      detailed kinetic analyses. A structure activity relationship (SAR) identified key
      atomic determinants (i.e. functional groups) important for inhibitory activity.
      Four "second series" analogs were selected and tested to validate our SAR and
      structural models. Here, we report improvements to inhibitory activity ranging
      between ~2- and 60-fold, resulting in selective low micromolar dengue protease
      inhibitors.

PMID- 21185333
TI  - Glucose-6-phosphate dehydrogenase is the target for the trypanocidal action of
      human steroids.
AB  - Steroids such as dehydroepiandrosterone (DHEA) and epiandrosterone (EA) exert
      multiple effects in mammals including the inhibition of glucose-6-phosphate
      dehydrogenase (G6PDH). Initially, the inhibition was considered specific for the
      mammalian enzyme. The beneficial effect of these steroids on infections by
      protists and nematodes was attributed to stimulation of the immune system.
      However, we showed previously that DHEA and EA also inhibit Trypanosoma brucei
      and T. cruzi G6PDH, with low micromolar K(i)' values, but not the enzyme from
      Leishmania species, and kill in vitro cultured trypanosomes. We report here that,
      contrary to wild-type trypanosomes, mutant bloodstream-form T. brucei cells
      expressing L. mexicana G6PDH are not susceptible to the steroids, proving that
      G6PDH is the in situ target. Moreover, bromo-derivatives of the steroids show 50
      100 fold lower K(i)' values for the enzyme and display an increased potency to
      kill the parasites. Therefore, the compounds offer promise for use in development
      of parasite-selective drugs.

PMID- 21185334
TI  - Mitochondrial oxidant stress triggers cell death in simulated ischemia
      reperfusion.
AB  - To clarify the relationship between reactive oxygen species (ROS) and cell death
      during ischemia-reperfusion (I/R), we studied cell death mechanisms in a cellular
      model of I/R. Oxidant stress during simulated ischemia was detected in the
      mitochondrial matrix using mito-roGFP, a ratiometric redox sensor, and by Mito
      Sox Red oxidation. Reperfusion-induced death was attenuated by over-expression of
      Mn-superoxide dismutase (Mn-SOD) or mitochondrial phospholipid hydroperoxide
      glutathione peroxidase (mito-PHGPx), but not by catalase, mitochondria-targeted
      catalase, or Cu,Zn-SOD. Protection was also conferred by chemically distinct
      antioxidant compounds, and mito-roGFP oxidation was attenuated by NAC, or by
      scavenging of residual O(2) during the ischemia (anoxic ischemia). Mitochondrial
      permeability transition pore (mPTP) oscillation/opening was monitored by real
      time imaging of mitochondrial calcein fluorescence. Oxidant stress caused release
      of calcein to the cytosol during ischemia, a response that was inhibited by
      chemically diverse antioxidants, anoxia, or over-expression of Mn-SOD or mito
      PHGPx. These findings suggest that mitochondrial oxidant stress causes
      oscillation of the mPTP prior to reperfusion. Cytochrome c release from
      mitochondria to the cytosol was not detected until after reperfusion, and was
      inhibited by anoxic ischemia or antioxidant administration during ischemia.
      Although DNA fragmentation was detected after I/R, no evidence of Bax activation
      was detected. Over-expression of the anti-apoptotic protein Bcl-X(L) in
      cardiomyocytes did not confer protection against I/R-induced cell death.
      Moreover, murine embryonic fibroblasts with genetic depletion of Bax and Bak, or
      over-expression of Bcl-X(L), failed to show protection against I/R. These
      findings indicate that mitochondrial ROS during ischemia triggers mPTP
      activation, mitochondrial depolarization, and cell death during reperfusion
      through a Bax/Bak-independent cell death pathway. Therefore, mitochondrial
      apoptosis appears to represent a redundant death pathway in this model of
      simulated I/R. This article is part of a Special Issue entitled: Mitochondria and
      Cardioprotection.

PMID- 21185335
TI  - Studies on the relationship between pulsed UV light irradiation and the
      simultaneous occurrence of molecular and cellular damage in clinically-relevant
      Candida albicans.
AB  - This constitutes the first study to report on the relationship between pulsed UV
      light (PL) irradiation and the simultaneous occurrence of molecular and cellular
      damage in clinical strains of Candida albicans. Microbial protein leakage and
      propidium iodide (PI) uptake assays demonstrated significant increases in cell
      membrane permeability in PL-treated yeast that depended on the amount of UV
      pulses applied. This finding correlated well with the measurement of increased
      levels of lipid hydroperoxidation in the cell membrane of PL-treated yeast. PL
      treated yeast cells also displayed a specific pattern of intracellular reactive
      oxygen species (ROS) generation, where ROS were initially localised in the
      mitochondria after low levels of pulsing (UV dose 0.82 MUJ/cm(2)) before more
      wide-spread cytosolic ROS production occurred with enhanced pulsing.
      Intracellular ROS levels were measured using the specific mitochondrial peroxide
      stain dihydrorhodamine 123 and the cytosolic oxidation stain dichloroflurescin
      diacetate. Use of the dihydroethidium stain also revealed increased levels of
      intracellular superoxide as a consequence of augmented pulsing. The ROS bursts
      observed during the initial phases of PL treatment was consistent with the
      occurrence of apoptotic cells as confirmed by detection of specific apoptotic
      markers, abnormal chromatin condensation and externalisation of cell membrane
      lipid phosphatidylserine. Increased amount of PL-irradiation (ca. UV does 1.24
      1.65 MUJ/cm(2)) also resulted in the occurrence of late apoptotic and necrotic
      yeast phenotypes, which coincided with the transition from mitochondrial to
      cytosolic localisation of ROS and with irreversible cell membrane leakage. Use of
      the comet assay also revealed significant nuclear damage in similarly treated PL
      samples. Although some level of cellular repair was observed in all test strains
      during sub-lethal exposure to PL-treatments (<=20 pulses or UV dose 0.55
      MUJ/cm(2)), this was absent in similar samples exposed to increased amounts of
      pulsing. This study showed that PL-irradiation inactivates C. albicans test
      strains through a multi-targeted process with no evidence of microbial ability to
      support cell growth after <=20 pulses. Implications of our findings in terms of
      application of PL for contact-surface disinfection are discussed.

PMID- 21185337
TI  - Pseudoislets in stirred-suspension culture exhibit enhanced cell survival,
      propagation and insulin secretion.
AB  - Cells from primary islets and beta-cell lines form pseudoislets (PIs) in static
      cultures. Interestingly, MIN6 beta-cells with aberrant regulation of
      proliferation form PIs which cease to grow after a week in culture. This growth
      arrest is attributed to a pro-apoptotic and anti-proliferative PI environment. We
      hypothesized that cell necrosis due to poor nutrient transport in dishes rather
      than apoptosis effects the observed PI size restriction. Formation of beta-cell
      PIs was explored in stirred-suspension bioreactors with enhanced mass transfer.
      Cells in stirred-suspension proliferated continuously and the PI size increased
      for two weeks. Bioreactor PIs displayed regulated basal insulin secretion and
      enhanced responsivity to glucose and incretins. Compared to dishes, cell
      viability in the bioreactor was higher with lower released lactate dehydrogenase
      activity. Similar expression of p21 and p27 in monolayers and PIs did not suggest
      an anti-proliferative PI milieu. Caspase-2, -8 and -9 activities were comparable
      in dish and bioreactor PIs, and the latter continued to grow after one week of
      culture. Thus, apoptosis is not sufficient to explain the differences in PI size
      between dishes and bioreactor. Moreover, the bioreactor method described here may
      be used to generate PIs with increased cell viability and function for research
      and clinical applications.

PMID- 21185336
TI  - Characterization of a rabbit polyclonal antibody against threonine-AMPylation.
AB  - An antibody against the posttranslational modification AMPylation was produced
      using a peptide corresponding to human Rac1 switch I region with AMPylated
      threonine-35 residue as an antigen. The resulting rabbit antiserum was tested for
      its abilities to recognize AMPylated proteins by western blot and
      immunoprecipitation. The antiserum is highly specific for threonine-AMPylated
      proteins and weakly recognizes tyrosine-AMPylated proteins. Depletion of serum
      with modified protein abolished its activity against tyrosine-AMPylated proteins.
      The antiserum also recognized native proteins with modification in an
      immunoprecipitation experiment. Interactions of the antiserum could be inhibited
      by competition with AMP but not with GMP or UMP. This antiserum had potential
      utility for the identification of unknown AMPylated proteins.

PMID- 21185338
TI  - Improvement of biohydrogen production by Enterobacter cloacae IIT-BT 08 under
      regulated pH.
AB  - The present study investigates the effect of pH and intermediate products
      formation on biological hydrogen production using Enterobacter cloacae IIT-BT 08.
      Initial pH was found to have a profound effect on hydrogen production potential,
      while regulating the pH 6.5 throughout the fermentation was found to increase the
      cumulative hydrogen production rate and yield significantly. Modified Gompertz
      equation was used to fit the cumulative hydrogen production curves to obtain the
      hydrogen production potential P, the hydrogen production rate R and lag phase
      lambda. At regulated pH 6.5, higher H(2) yield (3.1molH(2)mol(-1) glucose),
      specific hydrogen production potential (798.1mL/g) and specific rate of H(2)
      production (72.1mLL(-1)h(-1)g(-1)) were obtained. The volatile fatty acid profile
      showed butyrate, ethanol and acetate as the major end metabolites of fermentation
      under the operating pH conditions tested; however, their pattern of distribution
      was pH dependent. At the optimum pH of 6.5, the acetate to butyrate ratio (A/B
      ratio) was found to be higher than that at any other pH. The study also
      investigates the effect of sodium ions on biohydrogen production potential. It
      was also found that sodium ion concentration up to 250mM enhanced the hydrogen
      production potential; however, any further increase in the metal ion
      concentration had an inhibitory effect.

PMID- 21185339
TI  - Genome of turbot rhabdovirus exhibits unusual non-coding regions and an
      additional ORF that could be expressed in fish cell.
AB  - Genomic sequence of Scophthalmus maximus rhabdovirus (SMRV) isolated from
      diseased turbot has been characterized. The complete genome of SMRV comprises
      11,492 nucleotides and encodes five typical rhabdovirus genes N, P, M, G and L.
      In addition, two open reading frames (ORF) are predicted overlapping with P gene,
      one upstream of P and smaller than P (temporarily called Ps), and another in P
      gene which may encodes a protein similar to the vesicular stomatitis virus C
      protein. The C ORF is contained within the P ORF. The five typical proteins share
      the highest sequence identities (48.9%) with the corresponding proteins of
      rhabdoviruses in genus Vesiculovirus. Phylogenetic analysis of partial L protein
      sequence indicates that SMRV is close to genus Vesiculovirus. The first 13
      nucleotides at the ends of the SMRV genome are absolutely inverse
      complementarity. The gene junctions between the five genes show conserved
      polyadenylation signal (CATGA(7)) and intergenic dinucleotide (CT) followed by
      putative transcription initiation sequence A(A/G)(C/G)A(A/G/T), which are
      different from known rhabdoviruses. The entire Ps ORF was cloned and expressed,
      and used to generate polyclonal antibody in mice. One obvious band could be
      detected in SMRV-infected carp leucocyte cells (CLCs) by anti-Ps/C serum via
      Western blot, and the subcellular localization of Ps-GFP fusion protein exhibited
      cytoplasm distribution as multiple punctuate or doughnut shaped foci of uneven
      size.

PMID- 21185340
TI  - Chitosan-interferon-beta gene complex powder for inhalation treatment of lung
      metastasis in mice.
AB  - We prepared gene powders with chitosan as a non-viral vector and mannitol as a
      dry powder carrier to compare their gene expression and therapeutic efficacy to
      intravenous or intratracheal gene solutions using mice burdened with pulmonary
      metastasis prepared by injecting CT26 cells. The expression of a luciferase
      expression plasmid driven by the cytomegalovirus promoter (pCMV-Luc) and plasmid
      DNA encoding farnesylated enhanced green fluorescent protein (pEGFP-F) suggested
      that the genes expressed in both normal and tumorous tissues and the
      intratracheal powder resulted in higher expression than the intravenous or
      intratracheal solution. The intravenous and intratracheal solutions and the
      intratracheal powder of pCMV-Mubeta encoding murine interferon-beta were
      administered the day after the inoculation of mice with CT26 cells. Lung weight
      and the number of pulmonary nodules at day 21 were significantly suppressed by
      the three formulations at a dose of 10 MUg (N/P = 5). Reducing the dose to 1 MUg
      resulted in a loss of effect by the intravenous solution; however, the
      intratracheal formulations, especially the powder, were still effective. The
      intratracheal powder of pCMV-Mubeta at a dose of 1 MUg administered on day 1
      significantly extended mean survival time compared to the untreated control.
      These findings showed that therapeutic gene powders are promising for gene
      therapy to treat lung cancer or metastasis.

PMID- 21185341
TI  - The inflammatory microenvironment of HCC - the plot becomes complex.

PMID- 21185342
TI  - Characterization of prolactin-releasing peptide: binding, signaling and hormone
      secretion in rodent pituitary cell lines endogenously expressing its receptor.
AB  - The recently discovered prolactin-releasing peptide (PrRP) binds to the PrRP
      receptor and is involved in endocrine regulation and energy metabolism. However,
      its main physiological role is currently unknown. Two biologically active
      isoforms of PrRP exist: the 31 (PrRP31) and the 20 (PrRP20) amino acid forms,
      which both contain a C-terminal Phe amide sequence. In the present study, the
      PrRP receptor was immunodetected in three rodent tumor pituitary cell lines: GH3,
      AtT20 and RC-4B/C cells. The saturation binding of radioiodinated PrRP31 to
      intact cells demonstrated a K(d) in the 10(-9)M range and a B(max) in the range
      of tens of thousands binding sites per cell. For binding to RC-4B/C cells, both
      PrRP31 and PrRP20 competed with (125)I-PrRP31 with a similar K(i). The C-terminal
      analog PrRP13 showed lower binding potency compared to PrRP31 and PrRP20. All
      PrRP analogs increased the phosphorylation of MAPK/ERK1/2 (mitogen-activated
      phosphorylase/extracellular-regulated kinase) and CREB (cAMP response element
      binding protein) in RC-4B/C cells. Additionally, prolactin release was induced by
      the PrRP analogs in a dose-dependent manner in RC-4B/C cells. Finally, food
      intake after intracerebroventricular administration of PrRP analogs in fasted
      mice was followed. Both PrRP31 and PrRP20 decreased food intake, but PrRP13 did
      not show significant effect. Studies on pituitary cell lines expressing the PrRP
      receptor are more physiologically relevant than those on cells transfected with
      the receptor. This cell type can be used as a model system for pharmacological
      studies searching for PrRP antagonists and stable effective PrRP agonists, as
      these drugs may have potential as anti-obesity agents.

PMID- 21185343
TI  - Glucose-dependent insulinotropic peptide receptor expression in the hippocampus
      and neocortex of mesial temporal lobe epilepsy patients and rats undergoing
      pilocarpine induced status epilepticus.
AB  - The glucose-dependent insulinotropic peptide receptor (GIPR) has been implicated
      with neuroplasticity and may be related to epilepsy. GIPR expression was analyzed
      by immunohistochemistry in the hippocampus (HIP) and neocortex (Cx) of rats
      undergoing pilocarpine induced status epilepticus (Pilo-SE), and in three young
      male patients with left mesial temporal lobe epilepsy related to hippocampal
      sclerosis (MTLE-HS) treated surgically. A combined GIPR immunohistochemistry and
      Fluoro-Jade staining was carried out to investigate the association between the
      GIPR expression and neuronal degeneration induced by Pilo-SE. GIPR was expressed
      in the cytoplasm of neurons from the HIP CA subfields, dentate gyrus (DG) and Cx
      of animals and human samples. The GIPR expression after the Pilo-SE induction
      increases significantly in the HIP after 1h and 5 days, but not after 12h or 50
      days. In the Cx, the GIPR expression increases after 1h, 12h and 5 days, but not
      50 days after the Pilo-SE. The expression of GIPR 12h after Pilo-SE was inversely
      proportional to the Fluoro-Jade staining intensity. In the human tissue, GIPR
      expression patterns were similar to those observed in chronic Pilo-SE animals. No
      Fluoro-Jade stained cells were observed in the human sample. GIPR is expressed in
      human HIP and Cx. There was a time and region dependent increase of GIPR
      expression in the HIP and Cx after Pilo-SE that was inversely associated to
      neuronal degeneration.

PMID- 21185344
TI  - Functional expression of choline transporter-like protein 1 (CTL1) in human
      neuroblastoma cells and its link to acetylcholine synthesis.
AB  - We examined the molecular and functional characterization of choline uptake into
      human neuroblastoma cell lines (SH-SY5Y: non-cholinergic and LA-N-2: cholinergic
      neuroblastoma), and the association between choline transport and acetylcholine
      (ACh) synthesis in these cells. Choline uptake was saturable and mediated by a
      single transport system. Removal of Na(+) from the uptake buffer strongly
      enhanced choline uptake. Choline uptake was inhibited by the choline analogue
      hemicholinium-3 (HC-3) and various organic cations, and was significantly
      decreased by acidification of the extracellular medium. The increase in choline
      uptake under Na(+)-free conditions was inhibited by a Na(+)/H(+) exchanger (NHE)
      inhibitor. Real-time PCR revealed that choline transporter-like protein 1 (CTL1),
      NHE1 and NHE5 mRNA are mainly expressed. Western blot and immunocytochemical
      analysis indicated that CTL1 protein was expressed in plasma membrane. ChAT mRNA
      was expressed at a much higher level in LA-N-2 cells than in SH-SY5Y cells. The
      conversion of choline to ACh was confirmed in both cells, and was enhanced in
      Na(+)-free conditions. These findings suggest that CTL1 is functionally expressed
      in both SH-SY5Y and LA-N-2 cells and is responsible for choline uptake that
      relies on a directed H(+) gradient as a driving force, and this transport
      functions in co-operation with NHE1 and NHE5. Furthermore, choline uptake through
      CTL1 is associated with ACh synthesis in cholinergic neuroblastoma cells.

PMID- 21185345
TI  - Derlin-1 overexpression ameliorates mutant SOD1-induced endoplasmic reticulum
      stress by reducing mutant SOD1 accumulation.
AB  - Unfolded protein responses, including induction of stress sensor kinases,
      chaperones, and apoptotic mediators, are involved in the familial amyotrophic
      lateral sclerosis (ALS) model related to mutant Cu/Zn superoxide dismutase (SOD1)
      and sporadic ALS. We hypothesized that the endoplasmic reticulum-resident factor
      Derlin-1 plays a pivotal role in the regulation of misfolded proteins evoked by
      mutant SOD1. We show that Derlin-1 overexpression reduced mutant SOD1-induced
      cell toxicity and increased cell viability by suppressing the activation of the
      ER stress pathway factors: immunoglobulin-binding protein, activating
      transcription factor 6 p50, and C/EBP homologous protein. Interestingly,
      exogenous Derlin-1 resulted in a decrease in the amount of mutant SOD1, and a
      lesser decrease in that of wild-type SOD1, in transfected cells. Reduced SOD1
      protein expression was observed in the microsomal fraction of wild-type and
      mutant SOD1 cells. Our results indicate that Derlin-1 regulates the turn over of
      SOD1 by promoting the proteasomal and autophagosomal degradation of SOD1 protein,
      but not by decreasing mutant SOD1 mRNA levels. Insights into the effects of
      Derlin-1 on mutant SOD1 may facilitate advancements in the treatment of motor
      neuron degeneration associated with ALS.

PMID- 21185346
TI  - The new '5-HT' hypothesis of depression: cell-mediated immune activation induces
      indoleamine 2,3-dioxygenase, which leads to lower plasma tryptophan and an
      increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of
      which contribute to the onset of depression.
AB  - This paper reviews the body of evidence that not only tryptophan and consequent 5
      HT depletion, but also induction of indoleamine 2,3-dioxygenase (IDO) and the
      detrimental effects of tryptophan catabolites (TRYCATs) play a role in the
      pathophysiology of depression. IDO is induced by interferon (IFN)gamma,
      interleukin-6 and tumor necrosis factor-alpha, lipopolysaccharides and oxidative
      stress, factors that play a role in the pathophysiology of depression. TRYCATs,
      like kynurenine and quinolinic acid, are depressogenic and anxiogenic; activate
      oxidative pathways; cause mitochondrial dysfunctions; and have neuroexcitatory
      and neurotoxic effects that may lead to neurodegeneration. The TRYCAT pathway is
      also activated following induction of tryptophan 2,3-dioxygenase (TDO) by
      glucocorticoids, which are elevated in depression. There is evidence that
      activation of IDO reduces plasma tryptophan and increases TRYCAT synthesis in
      depressive states and that TDO activation may play a role as well. The
      development of depressive symptoms during IFNalpha-based immunotherapy is
      strongly associated with IDO activation, increased production of detrimental
      TRYCATs and lowered levels of tryptophan. Women show greater IDO activation and
      TRYCAT production following immune challenge than men. In the early puerperium,
      IDO activation and TRYCAT production are associated with the development of
      affective symptoms. Clinical depression is accompanied by lowered levels of
      neuroprotective TRYCATs or increased levels or neurotoxic TRYCATs, and lowered
      plasma tryptophan, which is associated with indices of immune activation and
      glucocorticoid hypersecretion. Lowered tryptophan and increased TRYCATs induce T
      cell unresponsiveness and therefore may exert a negative feedback on the primary
      inflammatory response in depression. It is concluded that activation of the
      TRYCAT pathway by IDO and TDO may be associated with the development of
      depressive symptoms through tryptophan depletion and the detrimental effects of
      TRYCATs. Therefore, the TRYCAT pathway should be a new drug target in depression.
      Direct inhibitors of IDO are less likely to be useful drugs than agents, such as
      kynurenine hydroxylase inhibitors; drugs which block the primary immune response;
      compounds that increase the protective effects of kynurenic acid; and specific
      antioxidants that target IDO activation, the immune and oxidative pathways, and 5
      HT as well.

PMID- 21185347
TI  - Predictors of treatment outcome in adults with ADHD treated with OROS(r)
      methylphenidate.
AB  - BACKGROUND: We conducted a post-hoc analysis of the Long-Acting MethylpheniDate
      in Adult attention-deficit hyperactivity disorder (LAMDA) study to investigate
      predictors of response in adults with ADHD randomly assigned to Osmotic Release
      Oral System (OROS)((r))-methylphenidate hydrochloride (MPH) 18, 36 or 72 mg or
      placebo. METHODS: LAMDA comprised a 5-week, double-blind (DB) period, followed by
      a 7-week, open-label (OL) period. A post-hoc analysis of covariance and a
      logistic regression analysis were undertaken to detect whether specific baseline
      parameters or overall treatment compliance during the double-blind phase
      contributed to response. The initial model included all covariates as independent
      variables; a backward stepwise selection method was used, with stay criteria of
      p<0.10. Six outcomes were considered: change from baseline CAARS:O-SV (physician
      rated) and CAARS:S-S (self-report) scores at DB and OL end points, and response
      rate (>=30% decrease in CAARS:O-SV score from baseline) and normalization of
      CAARS:O-SV score at DB end point. RESULTS: Taking into account a significant
      effect of OROS((r))-MPH treatment versus placebo in the original analysis
      (p<=0.015), across the outcomes considered in this post-hoc analysis, higher
      baseline CAARS scores were most strongly predictive of superior outcomes. Male
      gender and lower academic achievement were also predictive for improved results
      with certain outcomes. CONCLUSIONS: Several baseline factors may help to predict
      better treatment outcomes in adults receiving OROS((r))-MPH; however, further
      research is required to confirm these findings and examine their neurobiological
      underpinnings.

PMID- 21185348
TI  - Inhibition of Helicobacter pylori growth and its cytotoxicity by 2-hydroxy 4
      methoxy benzaldehyde of Decalepis hamiltonii (Wight & Arn); a new functional
      attribute.
AB  - Helicobacter pylori mediated gastric ulcer and cancers are common global problems
      since it was found to colonize in ~50% of gastric ulcer/cancer patients.
      Decalepis hamiltonii, (Asclepiadaceae family) extracts have been depicted with
      medicinal properties supporting the traditional knowledge of health beneficial
      attributes of D. hamiltonii. Previously we have shown that both aqueous as well
      as methanol extracts of D. hamiltonii containing abundant phenolics with
      predominant levels (20-40% of total phenolics) of 2-hydroxy-4-methoxy
      benzaldehyde (HMBA). Despite higher levels, HMBA contributed very little to the
      antioxidant activity (<10%) when compared to other phenolic compounds in the
      extract. In the current study we attempted to explore antimicrobial property,
      particularly anti-H. pylori activity, since traditional users document D.
      hamiltonii as a fighter of microbial infections. HMBA was isolated from the roots
      of D. hamiltonii by hydrodistillation and cold crystallization method; identified
      by HPLC and characterized using ESI-MS and confirmed by NMR studies as a compound
      of molecular mass 152 Da. Isolated HMBA was found to inhibit the growth of H.
      pylori, a potential ulcerogen in a dose dependent manner with MIC of ~39 MUg/mL
      as apposed to that of amoxicillin (MIC - 26 MUg/mL) for which H. pylori is
      susceptible. Results were further substantiated by the lysis of H. pylori by
      electron microscopy and electrophoretic studies. Studies on the mechanism of
      action indicated the counteracting effect of vacuolating toxin (VacA) of H.
      pylori which otherwise would lead to host cell cytotoxicity. Further the
      increased binding ability of HMBA to DNA and protein offered an impact on DNA
      protectivity and bioavailability. Results for the first time provide a direct
      evidence for anti-microbial attribute of HMBA. Insignificant antioxidant
      attribute of HMBA also reveals the anti-H. pylori activity via mechanisms other
      than antioxidative routes.

PMID- 21185349
TI  - Identification by photoaffinity labeling of the extracellular N-terminal domain
      of PAC1 receptor as the major binding site for PACAP.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) exerts many crucial
      biological functions through the interaction with its specific PAC1 receptor
      (PAC1-R), a class B G protein-coupled receptor (GPCR). To identify the binding
      sites of PACAP in the PAC1-R, three peptide derivatives containing a
      photoreactive p-benzoyl-phenylalanine (Bpa) residue were developed. These
      photosensitive PACAP analogs were fully biologically active and competent to
      displace radiolabeled Ac-PACAP27 from the PAC1-R. Subsequently, the (125)I
      labeled photoprobes were used to anchor the PAC1-R expressed in Chinese hamster
      ovary cells. Photolabeling led to the formation of two protein complexes of 76
      and 67 kDa, representing different glycosylated forms of the receptor. Proteinase
      and chemical cleavages of the peptide-receptor complexes revealed that
      (125)I[Bpa(0), Nle(17)]PACAP27, (125)I[Bpa(6), Nle(17)]PACAP27 and
      (125)I[Nle(17), Bpa(22)]PACAP27 covalently labeled the Ser(98) - Met(111)
      segment, the Ser(124) - Glu(125) dipeptide and the Ser(141) - Met(172) fragment,
      respectively. Taking into account the topology of the PAC1-R, these segments are
      mainly located within the extracellular N-terminal domain, indicating that this
      PAC1-R domain is the major binding site of PACAP27. The present study constitutes
      the first characterization of the binding domains of PACAP to its specific
      receptor and suggests heterogeneity within the binding mode of peptide ligands to
      class B GPCRs.

PMID- 21185350
TI  - Cognitive inefficiency in depressive undergraduates: stroop processing and ERPs.
AB  - Evidence from neuroimaging studies indicates that depressive symptomatology is
      associated with inefficient recruitment of prefrontal brain regions while
      performing tasks that tax executive function. In the current study, we
      investigated the time-course and ERP signature of inefficient executive
      functioning using a verbal Stroop color-naming task. Twenty (20) undergraduates
      with moderate to severe BDI-II depression scores and 20 low-scoring controls
      completed the task. Performance measures did not differ between the two groups.
      Overt reaction and P300 latencies indicated that all participants showed
      prominent Stroop effects, such that incongruent responses were delayed compared
      to congruent. Effects of task condition on the frontal N450 indicated that
      depressive participants differentiated congruent and incongruent trials earlier
      than did controls, and that the size of the congruency effect on the N450 was
      related to self-reported trait rumination among depressive participants.
      Following this effect, depressive participants showed larger P300s, suggesting an
      over-commitment of cognitive control resources in the depressive participants.
      These data lend further evidence to the cortical inefficiency hypothesis and
      extend the literature by indicating possible improper timing of neural
      activations during an executive task in depressive undergraduates.

PMID- 21185351
TI  - Hedonic reactivity to visual and olfactory cues: rapid facial electromyographic
      reactions are altered in anorexia nervosa.
AB  - Though it has been suggested that hedonic processing is altered in anorexia
      nervosa (AN), few studies have used objective measures to assess affective
      processes in this eating disorder. Accordingly, we investigated facial
      electromyographic, autonomic and subjective reactivity to the smell and sight of
      food and non-food stimuli, and assessed more particularly rapid facial reactions
      reflecting automatic processing of pleasantness. AN and healthy control (HC)
      women were exposed, before and after a standardized lunch, to pictures and
      odorants of foods differing in energy density, as well as to non-food sensory
      cues. Whereas the temporal profile of zygomatic activity in AN patients was
      typified by a fast drop to sensory cues within the 1000 ms following stimulus
      onset, HC showed a larger EMG reactivity to pictures in a 800-1000 ms time
      window. In contrast, pleasantness ratings discriminated the two groups only for
      high energy density food cues suggesting a partial dissociation between objective
      and subjective measures of hedonic processes in AN patients. The findings suggest
      that the automatic processing of pleasantness might be altered in AN, with the
      sensitivity to reward being modulated by controlled processes.

PMID- 21185353
TI  - Adaptation to bimanual asymmetric weights in isometric force coordination.
AB  - This study examined how different weighting coefficients imposed on individual
      finger force regulate bimanual finger force coordination patterns under the
      influence of bilateral coupling and visual information of the force output. The
      weighted sum of the two forces was computed as the total force output to match
      two target force levels (10% and 35% MVC) in separate conditions, and visual
      feedback of the total force output was provided in the experiment. The results
      revealed higher performance error at 35% in comparison with 10% MVC with the
      greatest error at the unequal coefficient setting. The correlation between the
      individual forces and the force output ratios correlated nonlinearly with the
      weighting coefficient ratios; however, the extent of change was much smaller than
      the coefficient ratios. The results suggest that bilateral coupling and task
      constraints interact to determine the coordination strategy. The irregularity of
      the individual finger forces increased with the weighting coefficient while the
      irregularity of the total force remained the same. The results support the
      hypothesis that the organization of redundant motor coordination patterns emerges
      from the interactive effect of the constraints on movement.

PMID- 21185354
TI  - Contingent negative variation and activation of postural preparation before
      postural perturbation by backward floor translation at different initial standing
      positions.
AB  - We investigated the effects of balance difficulty on contingent negative
      variation (CNV) and postural preparation against perturbation. Thirteen subjects
      were perturbed by a backward floor translation (S2) after an auditory warning
      stimulus. To alter balance difficulty, subjects maintained standing posture from
      four initial positions before perturbation. The position of the center of
      pressure in the anteroposterior direction (CoPy) was expressed as a percentage
      distance of foot length (%FL) from the heel: 10%FL anterior to extreme backward
      leaning; quiet standing (QS); and 20%FL and 10%FL posterior to extreme forward
      leaning. CNV, CoPy, and electromyography (EMG) of the lower leg muscles were
      analyzed. Balance difficulty was represented by the relative distance of the
      forward peak position of CoPy after S2 from the QS position. Balance difficulty
      was higher with a more anterior initial position. The late CNV peaked just before
      S2 (latency: -76 to -306 ms), then started becoming small. CNV peak was earlier
      and larger with increasing balance difficulty. CoPy backward shift and a
      continuous EMG increase were observed as the strategy for postural preparation,
      and were significantly earlier (61 ms and 42 ms, respectively) than the CNV peak.
      CNV peak time correlated closely with onset times of CoPy backward shift (r=0.78)
      and continuous EMG increase (r=0.71). These findings suggest that as balance
      difficulty increases, attentional allocation to sensory information and/or
      postural preparation starts earlier just before the perturbation.

PMID- 21185355
TI  - Violation of syntax and prosody--disentangling their contributions to the early
      left anterior negativity (ELAN).
AB  - The syntactic and prosodic information needed for auditory language comprehension
      is intertwined within the speech signal. Previous studies seeking to isolate
      automatic syntactic processes have reported an early left anterior negativity
      (ELAN) between 100 and 200 ms elicited by syntactic phrase structure violations.
      Although prosody was already well controlled in these studies, a change in the
      fundamental frequency (F(0)) contour occurred together with the syntactic
      violation. The present magnetoencephalography study aimed to disentangle the
      influence of these two superimposed processes. Responses elicited by a syntactic
      phrase structure violation were compared to responses elicited by a prosodically
      incongruent change in the sentence's F(0) contour in order to estimate the
      contribution of a prosodic incongruency to the ELAN effect. While both violations
      elicited stronger superior temporal cortex activation than correct sentences in a
      110-160 ms time window, the syntax violation effect was larger than the prosody
      violation effect and showed a left hemispheric bias which was absent for the
      prosodic violation. Furthermore, only syntactically incorrect sentences elicited
      an additional very early effect in a preceding time window. Thus, the syntax
      violation effect found in the current and also in previous studies cannot be
      attributed to the detection of an unexpected prosodic contour, but rather
      reflects difficulties in local phrase structure building.

PMID- 21185356
TI  - Decreased CCAAT/enhancer binding protein beta expression inhibits the growth of
      glioblastoma cells.
AB  - C/EBPbeta is a leucine-zipper transcription factor implicated in the control of
      metabolism, development, cell differentiation, and proliferation. However, it
      remains unclear its role in tumor development. Here, we show that down-regulation
      of C/EBPbeta by RNA interference inhibits proliferation in the GL261 murine
      glioblastoma cell line, induces an arrest of the cell cycle at the G0/G1
      boundary, and diminishes their transformation capacity and migration. In
      addition, we show that C/EBPbeta regulates the expression of several DNA damage
      response- and invasion-related genes. Lastly, C/EBPbeta depletion significantly
      retards tumor onset and prolongs survival in a murine orthotopic brain tumor
      model. Immunohistochemical analysis revealed a significant diminution of
      proliferating cell nuclear antigen (PCNA) labeling in tumors derived from
      C/EBPbeta-depleted GL261 cells compared with that in controls. These results
      show, for the first time, the dependence of glioma cells on C/EBPbeta and suggest
      a potential role of this transcription factor in glioma development.

PMID- 21185357
TI  - NR2A subunit of the N-methyl D-aspartate receptors are required for potentiation
      at the mossy fiber to granule cell synapse and vestibulo-cerebellar motor
      learning.
AB  - Traditionally studies aimed at elucidating the molecular mechanisms underlying
      cerebellar motor learning have been focused on plasticity at the parallel fiber
      to Purkinje cell synapse. In recent years, however, the concept is emerging that
      formation and storage of memories are both distributed over multiple types of
      synapses at different sites. Here, we examined the potential role of potentiation
      at the mossy fiber to granule cell synapse, which occurs upstream to plasticity
      in Purkinje cells. We show that null-mutants of N-methyl d-aspartate-NR2A
      receptors (NMDA-NR2A(-/-) mice) have impaired induction of postsynaptic long-term
      potentiation (LTP) at the mossy fiber terminals and a reduced ability to raise
      the granule cell synaptic excitation, while the basic excitatory output of the
      mossy fibers is unaffected. In addition, we demonstrate that these NR2A(-/-)
      mutants as well as mutants in which the C terminal in the NR2A subunit is
      selectively truncated (NR2A(DeltaC/DeltaC) mice) have deficits in phase reversal
      adaptation of their vestibulo-ocular reflex (VOR), while their basic eye movement
      performance is similar to that of wild type littermates. These results indicate
      that NMDA-NR2A mediated potentiation at the mossy fiber to granule cell synapse
      is not required for basic motor performance, and they raise the possibility that
      it may contribute to some forms of vestibulo-cerebellar memory formation.

PMID- 21185358
TI  - The influence of temporal asynchrony on multisensory integration in the
      processing of asynchronous audio-visual stimuli of real-world events: an event
      related potential study.
AB  - In this study, we manipulated the temporal asynchrony between auditory and visual
      inputs, and contrasted event-related potentials (ERPs) evoked by multisensory
      stimuli with the summation of the ERPs evoked by unisensory-auditory (A) and
      unisensory-visual (V) stimuli with the same temporal asynchrony. Our goal was to
      investigate the influence of temporal asynchrony on multisensory integration. In
      our experiment, the auditory and visual inputs in the multisensory stimuli had a
      stimulus onset asynchrony (SOA) of -300 ms, 0 ms, or 300 ms. The results
      suggested that when the auditory and visual inputs were synchronous, multisensory
      integrations would occur in the time windows of 110-160 ms, 210-250 ms and 300
      350 ms after auditory onset. When the auditory onset preceded the critical action
      onset by 300 ms, multisensory integrations were involved in the time windows of
      110-160 ms and 300-350 ms after auditory onset. When the critical action onset
      preceded the auditory onset by 300 ms, multisensory integrations would occur in
      the time windows of 110-160 ms, 210-250 ms, 290-320 ms and 350-400 ms after
      auditory onset. In addition, in the time windows of 110-160 ms and 210-250 ms,
      the integrations were stronger when the auditory and visual inputs were
      synchronous, and in the time window of 250-400 ms, multisensory integrations
      would be different as the SOAs were different. It was suggested that multisensory
      integration would occur regardless of the asynchrony between auditory and visual
      inputs, and multisensory integration could be influenced by temporal asynchrony.

PMID- 21185359
TI  - Bone morphogenetic protein receptor expressions in the adult rat brain.
AB  - Bone morphogenetic proteins (BMP) are members of the transforming growth factor
      beta (TGF-beta) superfamily. BMPs exert its biological functions by interacting
      with membrane bound receptors belonging to the serine/threonine kinase family
      including bone morphogenetic protein receptor I (BMPRIA, BMPRIB) and type II
      (BMPRII). Although BMPR expressions have been well described in the early
      development of the CNS, little information is available for their expressions in
      the adult CNS. We, thus, investigated BMPR expressions in the adult rat CNS using
      immunohistochemistry. Here, we show that BMPRIA, IB and II proteins are widely
      expressed throughout the adult CNS. Interestingly, we observed that BMPRIA, IB
      and II proteins are abundantly expressed in many kinds of axons. In addition, we
      found that BAMRIB-IR was preferentially expressed in dendrites of many neurons
      throughout the CNS, while BMPRIA was mainly expressed in cell bodies, showing
      that BMPRIA and BMPRIB are differentially targeted in a single neuron. In
      addition, besides abundant BMPR expressions in neurons, we exhibited BMPR
      expressions in astrocytes and ependymal cells. These data indicate that BMPRs are
      more widely expressed throughout the adult CNS than previously reported, and
      their continued abundant expressions in the adult brain strongly support the idea
      that BMPRs play pivotal roles also in the adult brain.

PMID- 21185360
TI  - Identification of the Plasmodium falciparum rhoptry neck protein 5 (PfRON5).
AB  - Gathering knowledge about the proteins involved in erythrocyte invasion by
      Plasmodium merozoites is the starting point for developing new strategies to
      control malarial disease. Many of these proteins have been studied in Toxoplasma
      gondii, where some belonging to the Moving Junction complex have been identified.
      This complex allows a strong interaction between host cell and parasite
      membranes, required for parasite invasion. In this genus, four rhoptry proteins
      (RON2, RON4, RON5 and RON8) and one micronemal protein (TgAMA-1) have been found
      as part of the complex. In Plasmodium falciparum, RON2 and RON4 have been
      characterized. In the present study, we identify PfRON5, a ~110 kDa protein which
      is expressed in merozoite and schizont stages of the FCB-2 strain.

PMID- 21185362
TI  - Molecular characterization and expression of a gene encoding cytosolic Hsp90 from
      Pennisetum glaucum and its role in abiotic stress adaptation.
AB  - Heat shock protein 90 (Hsp90) is an abundant and highly conserved molecular
      chaperone that is essential for viability in eukaryotes. They have a crucial role
      in the folding of a set of proteins involved in the regulation of many essential
      cellular pathways and also re-folding of stress-denatured polypeptides. However,
      their exact function is still not clearly elucidated. In this study the full
      length cDNA encoding for Hsp90 polypeptide and its corresponding gene was
      isolated from Pennisetum glaucum (designated PgHsp90). PgHsp90 cDNA encoded for a
      polypeptide of 698 amino acids with a predicted molecular mass of 80.3kDa and
      shared a high sequence homology (97-81%) to other plant cytosolic Hsp90s and
      shared less sequence homology (40-45%) to organelle and endoplasmic reticulum
      specific Hsp90 isoforms. A deduced amino acid sequence possessed three structural
      domains: N-terminus (1-211) ATP binding domain, middle (281-540) client protein
      interacting domain and C-terminus (541-698) dimerization domain; the N-terminus
      and middle domain is linked by a charged linker domain (212-280). It possesses
      the five-conserved amino acid signature sequence motifs characteristic of the
      Hsp90 family and a C-terminus MEEVD penta-peptide characteristic of the cytosolic
      Hsp90 isoform. The predicted quaternary architecture generated for PgHsp90
      through molecular modeling was globally akin to that of yeast Hsp90. The PgHsp90
      gene consists of 3 exons and 2 introns. The position and phasing of these introns
      were conserved in other plant cytosolic Hsp90 genes. Recombinant PgHsp90 protein
      was expressed in E. coli and purified to homogeneity, which possessed in vitro
      chaperone activity. E. coli expressing PgHsp90 protein showed enhanced tolerance
      to heat, salt and dehydration stresses. The quantitative up-regulation of PgHsp90
      gene expression positively correlates in response to different stresses to meet
      the additional demand for protein folding support. Cumulatively, the in vivo and
      in vitro experiments indicated that PgHsp90 plays an adaptive or protective role
      to counter the stress induced protein damage.

PMID- 21185361
TI  - Histone deacetylases in skeletal development and bone mass maintenance.
AB  - The skeleton is a multifunctional and regenerative organ. Dynamic activities
      within the bone microenvironment necessitate and instigate rapid and temporal
      changes in gene expression within the cells (osteoclasts, osteoblasts, and
      osteocytes) responsible for skeletal maintenance. Regulation of gene expression
      is controlled, in part, by histone deacetylases (Hdacs), which are intracellular
      enzymes that directly affect chromatin structure and transcription factor
      activity. Key roles for several Hdacs in bone development and biology have been
      elucidated though in vitro and in vivo models. Recent findings suggest that
      clinical usage of small molecule Hdac inhibitors for conditions like epilepsy,
      bipolar disorder, cancer, and a multitude of other ailments may have unintended
      effects on bone cell populations. Here we review the progress that has been made
      in the last decade in understanding how Hdacs contribute to bone development and
      maintenance.

PMID- 21185363
TI  - Phospholipid-polyaspartamide micelles for pulmonary delivery of corticosteroids.
AB  - A novel drug delivery system for beclomethasone dipropionate (BDP) has been
      constructed through self-assembly of a pegylated phospholipid-polyaminoacid
      conjugate. This copolymer was obtained by chemical reaction of alpha,beta-poly(N
      2-hydroxyethyl)-DL-aspartamide (PHEA) with 1,2-distearoyl-sn-glycero-3
      phosphoethanolamine-N-[amino(polyethyleneglycol)2000] (DSPE-PEG(2000)-NH(2)).
      Benefiting from the amphiphilic structure with the hydrophilic shell based on
      both PHEA and PEG and many hydrophobic stearoyl tails, PHEA-PEG(2000)-DSPE
      copolymer was able to self assemble into micelles in aqueous media above a
      concentration of 1.23 * 10(-7)M, determined by fluorescence studies. During the
      self-assembling process in aqueous solution, these structures were able to
      incorporate BDP, with a drug loading (DL) equal to 3.0 wt%. Once the empty and
      BDP-loaded micelles were prepared, a deep physicochemical characterization was
      carried out, including the evaluation of mean size, PDI, zeta potential,
      morphology and storage stability. Moreover, the excellent biocompatibility of
      both empty and drug-loaded systems was evaluated either on human bronchial
      epithelium (16HBE) or on red blood cells. The cellular uptake of BDP, free or
      blended into PHEA-PEG(2000)-DSPE micelles, was also evaluated, evidencing a high
      drug internalization when entrapped into these nanocarriers and demonstrating
      their potential for delivering hydrophobic drugs in the treatment of pulmonary
      diseases.

PMID- 21185364
TI  - Interaction of folate-conjugated human serum albumin (HSA) nanoparticles with
      tumour cells.
AB  - Folic acid has been previously demonstrated to mediate intracellular nanoparticle
      uptake. Here, we investigated cellular uptake of folic acid-conjugated human
      serum albumin nanoparticles (HSA NPs). HSA NPs were prepared by desolvation and
      stabilised by chemical cross-linking with glutaraldehyde. Folic acid was
      covalently coupled to amino groups on the surface of HSA NPs by carbodiimide
      reaction. Preparation resulted in spherical HSA NPs with diameters of 239 +/- 26
      nm. As shown by size exclusion chromatography, 7.40 +/- 0.90 MUg folate was bound
      per mg HSA NPs. Cellular NP binding and uptake were studied in primary normal
      human foreskin fibroblasts (HFFs), the human neuroblastoma cell line UKF-NB-3,
      and the rat glioblastoma cell line 101/8 by fluorescence spectrophotometry, flow
      cytometry, and confocal laser scanning microscopy. Covalent conjugation of folic
      acid to HSA NPs increased NP uptake into cancer cells but not into HFFs. Free
      folic acid interfered with cancer cell uptake of folic acid-conjugated HSA NPs
      but not with uptake of folic acid-conjugated HSA NPs into HFFs. These data
      suggest that covalent linkage of folic acid can specifically increase cancer cell
      HSA NP uptake.

PMID- 21185365
TI  - Characterization, blood profile and biodistribution properties of surface
      modified PLGA nanoparticles of SN-38.
AB  - SN-38, the active metabolite of irinotecan, poses a challenge in terms of drug
      delivery due to its low solubility and labile lactone ring. The aim of this study
      was to develop a SN-38 nanoparticulate delivery system to evaluate the in vivo
      blood profile and biodistribution properties of nanoparticles (NPs). Poly lactide
      co-glycolide (PLGA) NPs that were covalently bound to polyethylene glycol-folate
      (PEG-FOL) were prepared, and their in vivo biodistribution in rats was
      investigated. Either the SN-38 solution or SN-38 NP suspension was administered
      intravenously into the tail vein at a dose of 2mg SN-38 eq./kg. As expected, SN
      38 NPs showed a higher plasma concentration in vivo when compared with free SN-38
      during a 24h period. Compared with the SN-38 solution, both folate targeted and
      non-targeted NPs exhibited superior drug concentration in body organs such as the
      liver, spleen, and lung at 1 and 8h post-administration.

PMID- 21185366
TI  - 'Every mother is a mini-doctor': ethnomedicinal uses of fish, shellfish and some
      other aquatic animals in Bangladesh.
AB  - AIM OF THE STUDY: This research article examines the zootherapeutic uses of fish,
      shellfish and some other aquatic animals in two fishing villages in Bangladesh
      one floodplain and one coastal. MATERIALS AND METHODS: The floodplain fishing
      village Volarkandi is located within the Hakaluki wetland ecosystem in the
      northern Bangladesh and is inhabited mostly by Muslim fishers, whereas the
      coastal fishing village Thakurtala is located on Moheskhali island and most of
      the inhabitants are caste-based Hindu fishers. Participatory techniques were used
      to collect and validate information from the key informants. RESULTS: The
      research revealed that, historically, fishers have used fish and other aquatic
      animals not only as food items for nutrition, but also to solve a host of
      physical problems and diseases. Fish and shellfish are widely used for their
      galactogogue and aphrodisiac properties, for quick recovery from long-time
      sickness, to enhance the 'intelligence level' of children, and to prevent and
      treat a host of diseases like night blindness, chicken pox, dysentery, piles,
      muscular inflammation, fistula, malaria, skin diseases and 'big belly' syndrome
      in children. Depending on the objective of the use, different parts of the animal
      body, its derivatives, or the whole animal are used. The research also clarified
      different forms of the recipes used. The socio-cultural construction of the
      ethnomedicinal uses and the distinct gender roles of the fisherwomen were
      analyzed. CONCLUSION: The research revealed that the aetiologies and the
      preventive measures against folk illness are socio-culturally embedded and such
      indigenous medical systems grow and are sustained as a situated body of knowledge
      within the boundaries of a typical world view framed by local culture and
      biodiversity.

PMID- 21185367
TI  - Testicular toxicity induced by a triple neurokinin receptor antagonist in male
      dogs.
AB  - Mechanism mediating the testicular toxicity induced by CS-003, a triple
      neurokinin receptor antagonist, was investigated in male dogs. Daily CS-003
      administrations showed testicular toxicity, such as a decrease in the sperm
      number, motility and prostate weight; and an increase in sperm abnormality,
      accompanying histopathological changes in the testis, epididymis and prostate. A
      single CS-003 administration suppressed plasma testosterone and LH levels in
      intact and castrated males. The suppressed LH release was restored by GnRH
      agonist injection, suggesting that pituitary sensitivity to GnRH is not impaired
      by CS-003. Treatment with SB223412, a neurokinin 3 receptor antagonist, caused a
      similar effect to CS-003, such as toxicity in the testis, prostate and epididymis
      and decreased plasma level of LH and testosterone. In conclusion, CS-003-induced
      testicular toxicity is caused by the inhibition of neurokinin B/neurokinin 3
      receptor signaling probably at the hypothalamic level in male dogs.

PMID- 21185368
TI  - Neuroprotection by the selective iNOS inhibitor GW274150 in a model of Parkinson
      disease.
AB  - Neuroinflammation and the activation of inducible nitric oxide synthase (iNOS)
      have been proposed to play a role in the pathogenesis of Parkinson disease (PD).
      In this study we investigated the effects of the selective iNOS inhibitor
      GW274150 in the 6-OHDA model of PD. 6-OHDA administration was associated with
      increased numbers of cells expressing iNOS. Administration of the iNOS inhibitor
      twice daily for 7 days, beginning 2 days after the 6-OHDA lesioning, led to a
      significant neuroprotection as shown by assessment of the integrity of the
      nigrostriatal system by tyrosine hydroxylase immunocytochemistry and HPLC
      assessment of striatal dopamine content. However, GW274150 displayed a bell
      shaped neuroprotective profile, being ineffective at high doses. 6-OHDA lesioning
      was associated with an increase in microglial activation as assessed by the MHC
      II antigen OX-6 and the number of matrix metalloproteinase 9 (MMP-9)
      immunopositive cells. NO is a known modulator of MMP-9, and iNOS inhibition was
      associated with decreased numbers of MMP-9-immunopositive cells, culminating in a
      reduction in the numbers of reactive microglia. Withdrawal of GW274150 for a
      further 7 days negated any neuroprotective effects of iNOS inhibition, suggesting
      that the damaging effects of inflammation last beyond 7 days in this model and
      the continued administration of the drug may be required.

PMID- 21185369
TI  - Mutational analysis of TRAF6 reveals a conserved functional role of the RING
      dimerization interface and a potentially necessary but insufficient role of RING
      dependent TRAF6 polyubiquitination towards NF-kappaB activation.
AB  - TRAF6 is an E3 ubiquitin ligase that plays a pivotal role in the activation of NF
      kappaB by innate and adaptive immunity stimuli. TRAF6 consists of a highly
      conserved carboxyl terminal TRAF-C domain which is preceded by a coiled coil
      domain and an amino terminal region that contains a RING domain and a series of
      putative zinc-finger motifs. The TRAF-C domain contributes to TRAF6
      oligomerization and mediates the interaction of TRAF6 with upstream signaling
      molecules whereas the RING domain comprises the core of the ubiquitin ligase
      catalytic domain. In order to identify structural elements that are important for
      TRAF6-induced NF-kappaB activation, mutational analysis of the TRAF-C and RING
      domains was performed. Alterations of highly conserved residues of the TRAF-C
      domain of TRAF6 did not affect significantly the ability of the protein to
      activate NF-kappaB. On the other hand a number of functionally important residues
      (L77, Q82, R88, F118, N121 and E126) for the activation of NF-kappaB were
      identified within the RING domain of TRAF6. Interestingly, several homologues of
      these residues in TRAF2 were shown to have a conserved functional role in TRAF2
      induced NF-kappaB activation and lie at the dimerization interface of the RING
      domain. Finally, whereas alteration of Q82, R88 and F118 compromised both the K63
      linked polyubiquitination of TRAF6 and its ability to activate NF-kappaB,
      alteration of L77, N121 and E126 diminished the NF-kappaB activating function of
      TRAF6 without affecting TRAF6 K63-linked polyubiquitination. Our results support
      a conserved functional role of the TRAF RING domain dimerization interface and a
      potentially necessary but insufficient role for RING-dependent TRAF6 K63-linked
      polyubiquitination towards NF-kappaB activation in cells.

PMID- 21185370
TI  - Mast cells and metabolic syndrome.
AB  - Mast cells are critical effectors in the development of allergic diseases and in
      many immunoglobulin E-mediated immune responses. These cells exert their
      physiological and pathological activities by releasing granules containing
      histamine, cytokines, chemokines, and proteases, including mast cell-specific
      chymase and tryptase. Like macrophages and T lymphocytes, mast cells are
      inflammatory cells, and they participate in the pathogenesis of inflammatory
      diseases such as cardiovascular complications and metabolic disorders. Recent
      observations suggested that mast cells are involved in insulin resistance and
      type 2 diabetes. Data from animal models proved the direct participation of mast
      cells in diet-induced obesity and diabetes. Although the mechanisms by which mast
      cells participate in these metabolic diseases are not fully understood,
      established mast cell pathobiology in cardiovascular diseases and effective mast
      cell inhibitor medications used in pre-formed obesity and diabetes in
      experimental models offer hope to patients with these common chronic inflammatory
      diseases. This article is part of a Special Issue entitled: Mast cells in
      inflammation.

PMID- 21185372
TI  - Peripheral analgesia: Hitting pain where it hurts.
AB  - Pain is a complex biological phenomenon that encompasses intricate
      neurophysiological, behavioural, psychosocial and affective components.
      Protracted or chronic pain alerts an individual to a possible pathological
      abnormality and is the main reason why patients visit a primary care physician.
      Despite the pervasiveness of chronic pain in the population, the effectiveness of
      current pharmacological therapies remains woefully inadequate and prolonged
      treatment often leads to the development of undesirable side-effects. Since the
      vast majority of chronic pain originates in a specific tissue or group of
      tissues, it may be advantageous to target pain control in the periphery and
      thereby circumvent the known risks associated with non-specific systemic
      treatments. This review spotlights a number of promising targets for peripheral
      pain control including the transient receptor potential (TRP) family of neuronal
      ion channels, the family of proteinase activated receptors (PARs), cannabinoids,
      and opioids. A critical appraisal of these targets in preclinical models of
      disease is given and their suitability as future peripheral analgesics is
      discussed.

PMID- 21185373
TI  - The production of 'aerodynamically equivalent' drug and excipient inhalable
      powders using a novel fractionation technique.
AB  - Inhalation particles can be produced by various techniques such as milling,
      controlled crystallisation and spray-drying, but current methods cannot, to-date,
      precisely control the aerodynamic size distribution of produced powders. The aim
      of this study was to develop and validate a novel preparative technique whereby
      the efficient and reproducible aerodynamic fractionation of drug and excipient
      powders could be achieved. Salmeterol xinafoate (SX), fluticasone propionate (FP)
      and fine alpha-lactose monohydrate (FL) were chosen as model compounds. Powders
      were aerosolised using a dry powder feeder into a Next Generation Impactor
      operated at 60 L min(-1). Powders deposited on NGI stages were then collected and
      analysed. The fractionation process was successful for all powders producing
      significant linear correlations between the pre-set aerodynamic cut-off limits
      and geometric size measurements. For each of SX, FP and FL, sufficient powder
      quantities were recovered from NGI stages 1-6 producing six fractions with
      sequential aerodynamic and geometric particle size distributions. The
      fractionation technique was efficient and reproducible for all powders studied.
      The method can be equally applied to various drugs and excipients regardless of
      their previous production/processing history. Therefore, the aerodynamic
      fractionation technique may be used to compare and contrast samples produced by
      different processes.

PMID- 21185374
TI  - Persistent and non-persistent changes in gene expression result from long-term
      estrogen exposure of MCF-7 breast cancer cells.
AB  - Life-long estrogen exposure is recognized as a major risk factor for the
      development of breast cancer. While the initial events in the regulation of gene
      expression by estrogen have been described in detail, far less is known of the
      role of estrogen in the long-term regulation of gene expression. In this study,
      we investigated the effects of long-term exposure of MCF-7 breast cancer cells to
      1nM 17beta-estradiol on gene expression with the goal of distinguishing between
      gene expression that is continually reliant on estrogen receptor (ER) function as
      opposed to secondary and persistent effects that are downstream of ER. To assess
      the direct involvement of ER in the differential gene expression of long-term
      estrogen exposed (LTEE) cells in comparison with that of control cells, we
      exposed cultures to the selective estrogen receptor modulator raloxifene (RAL).
      cDNA microarray analysis showed that exposure to RAL inhibited expression of
      numerous characterized estrogen-regulated genes, including PGR, GREB1, and PDZK1.
      Genes that were increased in expression in LTEE cells yet were unaffected by RAL
      exposure included the aryl hydrocarbon receptor (AHR) and numerous other genes
      that were not previously reported to be regulated by estrogen. Epigenetic
      regulation was evident for the AHR gene; AhR transcript levels remained elevated
      for several cell passages after the removal of estrogen. Signal transducer and
      activator of transcription 1 (STAT1); STAT1-regulated genes including ISG15,
      IFI27, and IFIT1; and MHC class I genes were also up-regulated in LTEE cells and
      were unaffected by RAL exposure. STAT1 is commonly overexpressed in breast and
      other cancers, and is associated with increased resistance to radiation and
      chemotherapy. This is the first study to relate estrogen exposure to increased
      STAT1 expression in breast cancer cells, an effect that may represent an
      additional role of estrogen in the pathogenesis of breast cancer.

PMID- 21185375
TI  - Human adrenal cells that express both 3beta-hydroxysteroid dehydrogenase type 2
      (HSD3B2) and cytochrome b5 (CYB5A) contribute to adrenal androstenedione
      production.
AB  - Androstenedione is one of several weak androgens produced in the human adrenal
      gland. 3beta-Hydroxysteroid dehydrogenase type 2 (HSD3B2) and cytochrome b5
      (CYB5A) are both required for androstenedione production. However, previous
      studies demonstrated the expression of HSD3B2 within the zona glomerulosa (ZG)
      and fasciculata (ZF) but low levels in the zona reticularis. In contrast, CYB5A
      expression increases in the zona reticularis (ZR) in human adrenal glands.
      Although their colocalization has been reported in gonadal theca and Leydig cells
      this has not been studied in the human adrenal. Therefore, we immonolocalized
      HSD3B2 and CYB5A in normal human adrenal glands and first demonstrated their co
      expression in the cortical cells located at the border between the ZF and ZR in
      normal human adrenal. Results of in vitro studies using the human adrenal H295R
      cells treated with the HSD3B2 inhibitor, trilostane, also demonstrated a markedly
      decreased androstenedione production. Decreasing CYB5A mRNA using its
      corresponding siRNA also resulted in significant inhibition of androstenedione
      production in the H295R cells. These findings together indicate that there are a
      group of cells co-expressing HSD3B2 and CYB5A with hybrid features of both ZF and
      ZR in human adrenal cortex, and these hybrid cortical cells may play an important
      role in androstenedione production in human adrenal gland.

PMID- 21185376
TI  - Endothelins & erectile dysfunction.
AB  - Erectile dysfunction (ED) is common and a significant contributor to poor quality
      of life and psychosocial morbidity in men. Normal erectile function requires
      effective co-ordination between a number of complex neural pathways. Penile
      tumescence occurs in response to rapid arterial inflow to the corpora cavernosa
      with simultaneous venous outflow restriction due to expansion of the lacunar
      spaces. This process is under both central and local neuromediation. Endothelins
      are potent vasoconstrictor peptides that cause strong, slowly developing but
      sustained contraction of trabecular smooth muscles cells of the corpora
      cavernosa. Multiple mechanisms of action are proposed, including transmembrane
      calcium flux, mobilisation of inositol triphosphate sensitive intracellular
      calcium stores and calcium sensitisation through the Rho-Rho kinase pathway. The
      exact role of endothelins in the pathogenesis of ED currently remains unclear.
      Elevated endothelin-1 levels are found in patients with diabetes mellitus and
      this alone may be sufficient to cause ED. However, this is not borne out in
      clinical studies. The resultant elevated intracellular calcium may, however,
      modulate gene expression sufficiently to cause smooth muscle proliferation.
      Alternatively, alterations in endothelin receptor sensitivity in conditions such
      as diabetes and hypertension may enhance vasoconstrictor processes. Currently
      there is contradictory evidence for the role of endothelin receptor antagonists
      in ED. Animals studies suggest they inhibit corporal vasoconstriction, improve
      erectile function and protect against diabetes-induced smooth muscle apoptosis.
      However, the results of clinical studies in ED have been less promising.
      Uncertainty regarding the exact role of endothelin in penile erection hampers
      progress in this area. It is possible that the endothelin system may only be
      relevant to ED in certain conditions where global endothelial dysfunction exists
      (e.g. diabetes mellitus, systemic sclerosis) and the use of endothelin
      antagonists in these patient groups may yield improved outcomes.

PMID- 21185377
TI  - Genetic screens using the piggyBac transposon.
AB  - Transposons are an attractive system to use in genetic screens as they are
      molecularly tractable and the disrupted loci that give rise to the desired
      phenotype are easily mapped. We consider herein the characteristics of the
      piggyBac transposon system in complementing existing mammalian screen strategies,
      including the Sleeping Beauty transposon system. We also describe the design of
      the piggyBac resources that we have developed for both forward and reverse
      genetic screens, and the protocols we use in these experiments.

PMID- 21185371
TI  - Mast cells and inflammation.
AB  - Mast cells are well known for their role in allergic and anaphylactic reactions,
      as well as their involvement in acquired and innate immunity. Increasing evidence
      now implicates mast cells in inflammatory diseases where they are activated by
      non-allergic triggers, such as neuropeptides and cytokines, often exerting
      synergistic effects as in the case of IL-33 and neurotensin. Mast cells can also
      release pro-inflammatory mediators selectively without degranulation. In
      particular, IL-1 induces selective release of IL-6, while corticotropin-releasing
      hormone secreted under stress induces the release of vascular endothelial growth
      factor. Many inflammatory diseases involve mast cells in cross-talk with T cells,
      such as atopic dermatitis, psoriasis and multiple sclerosis, which all worsen by
      stress. How mast cell differential responses are regulated is still unresolved.
      Preliminary evidence suggests that mitochondrial function and dynamics control
      mast cell degranulation, but not selective release. Recent findings also indicate
      that mast cells have immunomodulatory properties. Understanding selective release
      of mediators could explain how mast cells participate in numerous diverse
      biologic processes, and how they exert both immunostimulatory and
      immunosuppressive actions. Unraveling selective mast cell secretion could also
      help develop unique mast cell inhibitors with novel therapeutic applications.
      This article is part of a Special Issue entitled: Mast cells in inflammation.

PMID- 21185378
TI  - Targeted genome editing in pluripotent stem cells using zinc-finger nucleases.
AB  - Zinc-finger nucleases (ZFNs) are designer nucleases capable of cleaving a
      prespecified target DNA within complex genomes. ZFNs consist of a non-specific
      endonuclease domain fused to an engineered DNA-binding domain that tethers the
      nuclease activity to the chosen chromosomal site. The endonuclease-induced DNA
      double strand break triggers a cellular DNA damage response, resulting in double
      strand break repair by either accurate homologous recombination (HR) or error
      prone non-homologous end-joining (NHEJ). Thus, ZFNs are powerful tools for
      targeted genome engineering in a variety of mammalian cell types, including
      embryonic (ESCs) and induced pluripotent stem cells (iPSCs). As a paradigm for
      genome editing in pluripotent stem cells, we describe the use of ZFNs in murine
      ESCs for generating knockout alleles by NHEJ without selection or by HR employing
      different selection schemes.

PMID- 21185379
TI  - PhiC31 integrase facilitates genetic approaches combining multiple recombinases.
AB  - Homologous and site-specific DNA recombination has revolutionized genetic
      engineering. The reliability of recombinases such as Cre and FLP has allowed
      scientists to design complex strategies to study gene function in mammals.
      However, the retention of recombination sites in the genome limits the use of Cre
      and FLP recombinases in subsequent modifications. Access to additional
      recombinases in the ES cell toolbox would enormously widen the number of
      possibilities to manipulate the genome. In the method presented here, we combine
      the use of PhiC31, a site-specific integrase, with FLP to obtain site-specific
      insertion and replacement in pre-inserted docking sites in the genome of mouse ES
      cells. This method allows for the integration of any sequence of interest in a
      pre-defined locus, leaving Cre recombinase available for downstream applications.
      The selection strategy is based on a silent selection marker activated by a
      plasmid-delivered promoter, making the integration system highly reliable and
      reducing the need for extensive molecular screens. This article describes how to
      create "dockable" mouse embryonic stem (ES) cell lines, integrate incoming
      vectors, and analyze the resulting clones. Current applications of this
      technology are also discussed.

PMID- 21185380
TI  - Mouse mutants and phenotypes: accessing information for the study of mammalian
      gene function.
AB  - Recent advances in high-throughput gene targeting and conditional mutagenesis are
      creating new and powerful resources to study the in vivo function of mammalian
      genes using the mouse as an experimental model. Mutant ES cells and mice are
      being generated at a rapid rate to study the molecular and phenotypic
      consequences of genetic mutations, and to correlate these study results with
      human disease conditions. Likewise, classical genetics approaches to identify
      mutations in the mouse genome that cause specific phenotypes have become more
      effective. Here, we describe methods to quickly obtain information on what mutant
      ES cells and mice are available, including recombinase driver lines for the
      generation of conditional mutants. Further, we describe means to access genetic
      and phenotypic data that identify mouse models for specific human diseases.

PMID- 21185381
TI  - Genetic engineering of mammalian cells by direct delivery of FLP recombinase
      protein.
AB  - Protein transduction is based on the ability of certain peptides, designated as
      cell penetrating peptides (CPPs), to intracellularly deliver cargo molecules,
      such as peptides and proteins. In combination with site specific recombination,
      CPP-mediated delivery of recombinases enables a precise and highly efficient
      control of gene expression in cultured cells and mice. Herein, we provide
      detailed protocols for engineering and purification of a cell-permeant FLP
      recombinase protein. Two examples describe the use of cell permeant FLP for
      excising prespecified fragments from transgenes expressed in fibroblasts and
      mouse embryonic stem cells. A third example describes the combined use of cell
      permeant Cre and FLP recombinases to reversibly induce transgenes in embryonic
      stem cells. We anticipate that the protocols described herein will be widely used
      for various genetic interventions addressing complex biological questions.

PMID- 21185382
TI  - High-throughput mouse phenotyping.
AB  - Comprehensive phenotyping will be required to reveal the pleiotropic functions of
      a gene and to uncover the wider role of genetic loci within diverse biological
      systems. The challenge will be to devise phenotyping approaches to characterise
      the thousands of mutants that are being generated as part of international
      efforts to acquire a mutant for every gene in the mouse genome. In order to
      acquire robust datasets of broad based phenotypes from mouse mutants it is
      necessary to design and implement pipelines that incorporate standardised
      phenotyping platforms that are validated across diverse mouse genetics centres or
      mouse clinics. We describe here the rationale and methodology behind one
      phenotyping pipeline, EMPReSSslim, that was designed as part of the work of the
      EUMORPHIA and EUMODIC consortia, and which exemplifies some of the challenges
      facing large-scale phenotyping. EMPReSSslim captures a broad range of data on
      diverse biological systems, from biochemical to physiological amongst others.
      Data capture and dissemination is pivotal to the operation of large-scale
      phenotyping pipelines, including the definition of parameters integral to each
      phenotyping test and the associated ontological descriptions. EMPReSSslim data is
      displayed within the EuroPhenome database, where a variety of tools are available
      to allow the user to search for interesting biological or clinical phenotypes.

PMID- 21185384
TI  - High-throughput RNAi screening in mammalian cells with esiRNAs.
AB  - The development of advanced functional genomic tools has paved the way for
      systematic investigations of biological processes in health and disease. In
      particular, the implementation of RNA interference (RNAi) as a genome-wide, loss
      of-function screening tool has enabled scientists to probe the role for every
      gene in cellular assays and many new factors for various processes have been
      discovered employing RNAi screens in recent years. However, the results also
      demonstrate the complexity of biological systems and indicate that we are still a
      long way from understanding functional networks in depth. Nevertheless, RNAi
      screens present a powerful method to interrogate gene function in high-throughput
      and different methods to elicit RNAi in mammalian cells have been developed.
      Here, we describe steps that should be considered when planning an RNAi screen
      employing endoribonuclease prepared (e)siRNAs. We provide useful information on
      how to implement the screen and analyze the results. Furthermore, we discuss
      strategies for hit validation and present an outline on how to follow-up on
      verified hits to gain a molecular understanding of the underlying phenotypes.

PMID- 21185383
TI  - High-throughput analysis of gene expression on tissue sections by in situ
      hybridization.
AB  - Genome-scale sequencing projects, high-throughput RNAi screens, systematic gene
      targeting, and system-biology-based network predictions all depend on a
      validation of biological significance in order to understand the relevance of a
      particular finding. Such validation, for the most part, rests on low-throughput
      technologies. This article provides protocols that, in combination with suitable
      instrumentation, make possible a semi-automated analysis of gene expression on
      tissue sections by means of in situ hybridization. Knowledge of gene expression
      localization has the potential to aid, and thereby accelerate, the validation of
      gene functions.

PMID- 21185385
TI  - Comparative expression of wild-type and highly soluble mutant His103Leu of
      hydroxynitrile lyase from Manihot esculenta in prokaryotic and eukaryotic
      expression systems.
AB  - Low protein solubility and inclusion body formation represent big challenges in
      production of recombinant proteins in Escherichia coli. We have recently reported
      functional expression of hydroxynitrile lyase from Manihot esculenta, MeHNL, in
      E. coli with high in vivo solubility and activity using directed evolution. As a
      part of attempts to clarify the mechanism of this phenomenon, we have described
      the possibility of expression of the highly active and soluble mutant MeHNL
      His103Leu as well as wild-type enzyme in several expression systems.
      Methylotrophic yeast Pichia pastoris, protozoan host Leishmania tarentolae and
      two cell-free translations, including an E. coli lysate (WakoPURE system) and
      wheat germ translation system were used to compare expression profiles of the
      genes. Two distinguishable protein expression patterns were observed in
      prokaryotic and eukaryotic-based systems. The wild-type and mutant enzyme showed
      high activity for both genes (up to 10 U/ml) in eukaryotic hosts P. pastoris and
      L. tarentolae, while those of E. coli exhibited about 1 and 15 U/ml,
      respectively. The different activity level in prokaryotic systems but the same
      level among the eukaryotic hosts indicate the phenomenon is specific to the E.
      coli system. Both the wild-type and mutant enzymes were functionally expressed in
      eukaryotic systems, probably using the folding assistants such as chaperones.
      Properties of expression systems used in this study were precisely compared, too.

PMID- 21185386
TI  - The g-type lysozyme of Scophthalmus maximus has a broad substrate spectrum and is
      involved in the immune response against bacterial infection.
AB  - Lysozyme is a muramidase that inflicts damage on bacterial cell wall by
      catalyzing the cleavage of the beta-1,4-glycosidic bond between N-acetylmuramic
      acid and N-acetylglucosamine in peptidoglycan. Lysozymes are classified into
      several types, one of which is the goose-type (g-type). In this study, we
      identified and analyzed a g-type lysozyme (SmLysG) from turbot Scophthalmus
      maximus. The deduced amino acid sequence of SmLysG contains 193 residues and is
      most closely related to that of the g-type lysozyme of Scophthalmus rhombus (94%
      overall identity). SmLysG possesses a Goose Egg White Lysozyme (GEWL) domain with
      conserved residues essential for catalytic activity. Recombinant SmLysG (rSmLysG)
      purified from yeast exhibits strong lysozyme activity against Micrococcus luteus.
      Enzyme assays showed that the optimal temperature and pH of rSmLysG are 30
      degrees C and pH 7.0, respectively. Substrate spectrum analysis indicated that
      rSmLysG inhibited the growth of a number of important fish pathogens of both Gram
      negative and Gram-positive natures. SmLysG transcription was detected in multiple
      tissues and was upregulated in kidney and spleen by experimental challenges with
      lipopolysaccharide and bacterial pathogens that are, respectively, sensitive to
      and resistant against the lytic effect of rSmLysG. Comparative analysis showed
      that although bacterial infection also induced the expression of c-type lysozyme,
      the induction levels were much lower than those of SmLysG. Taken together, these
      results indicate that SmLysG is a functional g-type lysozyme with a wide working
      range and is involved in innate immune defense against general bacterial
      infection.

PMID- 21185388
TI  - The Lusitania Province as a center of diversification: the phylogeny of the genus
      Microlipophrys (Pisces: Blenniidae).
AB  - The Lusitania Province has been considered a transition zone between the Atlantic
      northern cold waters and Tropical warm waters. Tropical species have expanded
      their ranges during warm periods and either retreated during cold periods or
      survived in local refuges. Successive waves of dispersion into this Province
      could have favored diversification through geographic isolation. Taxa that
      remained in this large Province may also have diversified in loco. We analyzed
      molecular markers of the genus Microlipophrys (family Blenniidae) that confirm
      the validity of this genus and of the seven recognized species. Microlipophrys
      and its sister clade apparently originated within Lusitania and dispersed into
      the tropics at a later stage.

PMID- 21185387
TI  - Quantitative pharmacologic MRI: mapping the cerebral blood volume response to
      cocaine in dopamine transporter knockout mice.
AB  - The use of pharmacologic MRI (phMRI) in mouse models of brain disorders allows
      noninvasive in vivo assessment of drug-modulated local cerebral blood volume
      changes (DeltaCBV) as one correlate of neuronal and neurovascular activities. In
      this report, we employed CBV-weighted phMRI to compare cocaine-modulated neuronal
      activity in dopamine transporter (DAT) knockout (KO) and wild-type mice. Cocaine
      acts to block the dopamine, norepinephrine, and serotonin transporters (DAT, NET,
      and SERT) that clear their respective neurotransmitters from the synapses,
      helping to terminate cognate neurotransmission. Cocaine consistently reduced CBV,
      with a similar pattern of regional DeltaCBV in brain structures involved in
      mediating reward in both DAT genotypes. The largest effects (-20% to -30%
      DeltaCBV) were seen in the nucleus accumbens and several cortical regions.
      Decreasing response amplitudes to cocaine were noted in more posterior components
      of the cortico-mesolimbic circuit. DAT KO mice had significantly attenuated
      DeltaCBV amplitudes, shortened times to peak response, and reduced response
      duration in most regions. This study demonstrates that DAT knockout does not
      abolish the phMRI responses to cocaine, suggesting that adaptations to loss of
      DAT and/or retained cocaine activity in other monoamine neurotransmitter systems
      underlie these responses in DAT KO mice.

PMID- 21185389
TI  - Efficacy and safety of ciprofloxacin for prophylaxis of polyomavirus BK virus
      associated hemorrhagic cystitis in allogeneic hematopoietic stem cell
      transplantation recipients.
AB  - Polyoma virus BK-induced hemorrhagic cystitis is an important cause of morbidity
      after hematopoietic stem cell transplantation (HSCT). Fluoroquinolones have been
      shown in vitro to inhibit BK viral replication by direct inhibition of the BK
      encoded DNA gyrase. We hypothesized that extended prophylaxis with ciprofloxacin
      may decrease the incidence of severe (grades 3 and 4) BK virus-associated
      hemorrhagic cystitis (sBKHC) after HSCT. We retrospectively collected patient and
      transplant data, as well as incidence of sBKHC, for all consecutive patients
      undergoing allogeneic HSCT between June 2006 and August 2010 at our institution.
      Prophylaxis for sBKHC with ciprofloxacin 500 mg orally twice daily from day 0
      until day 60 had been instituted in March 2009, delimiting a group receiving
      ciprofloxacin prophylaxis (CP) or no prophylaxis (NP). We compared the cumulative
      incidence of sBKHC in CP and NP, including death in absence of sBKHC as a
      competing risk. Ninety-two consecutive patients were included in the analysis, 44
      in CP and 48 in NP. Median age of patients was 50 years (range: 19-70), and 47%
      received a myeloablative conditioning regimen. The cumulative incidence of sBKHC
      was significantly reduced in CP (2.6% versus 20.9%, P = .01). Multivariate Cox
      regression analysis revealed that assignment to CP and concomitant acute graft
      versus-host disease (GVHD) were the only factors independently associated with
      the occurrence of sBKHC. Patients in CP did not experience a higher risk of
      Clostridium difficile diarrhea and were less likely to develop episodes of
      bacteremia. Ciprofloxacin prophylaxis appears safe and effective in reducing the
      incidence of severe BKHC after allogeneic HSCT.

PMID- 21185390
TI  - Application of the DNA adductome approach to assess the DNA-damaging capability
      of in vitro micronucleus test-positive compounds.
AB  - The in vitro micronucleus (MN) test is widely used for screening genotoxic
      compounds, but it often produces false-positive results. To consider the
      significance of positive results, it is important to know whether DNA adducts are
      formed in the cells treated with the test compound. Recently, Matsuda et al.
      developed the DNA adductome approach to detect DNA adducts comprehensively ([4]
      Kanaly, et al., Antioxid. Redox Signal., 2006, 8, 993-1001). We applied this
      method to assess the DNA-damaging capability of in vitro MN test-positive
      compounds. CHL/IU cells were treated with compounds from three categories: (1)
      carcinogens causing DNA alkylation, ethyl methanesulfonate and N-methyl-N'-nitro
      N-nitrosoguanidine; (2) carcinogens producing DNA bulky adducts, 2-amino-6-phenyl
      1-methylimidazo[4,5-b]pyrene, benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, and
      4-nitroquinoline-1-oxide, and (3) non-carcinogens, caffeine, maltol, and sodium
      chloride, with or without metabolic activation. With the conditions in which all
      test compounds gave positive results in the MN tests, DNA was extracted from the
      cells and hydrolyzed to deoxyribonucleosides, which were subsequently subjected
      to LC/ESI-MS/MS analysis. All carcinogens (categories 1 and 2) produced various
      DNA adduct peaks, and some of the m/z peak values corresponded to known adducts.
      No non-carcinogens produced DNA adducts, indicating that these compounds produced
      MN through different mechanisms from the adduct formation. These results indicate
      that the adductome approach is useful to demonstrate DNA damage formation of MN
      test-positive compounds and to understand their mechanisms of action.

PMID- 21185391
TI  - Genotoxicity of sodium metabisulfite in mouse tissues evaluated by the comet
      assay and the micronucleus test.
AB  - Sodium metabisulfite (SMB, Na(2)S(2)O(5)) is widely used in the food and
      pharmaceutical industries, because of its ability to inhibit proliferation of
      microorganisms and its antioxidant properties. We have evaluated the genotoxic
      effects of SMB on different tissues of the mouse, by use of the comet assay
      (liver and blood cells) and the micronucleus test (blood and bone marrow cells).
      For all tissues, significant increases in damage index and damage frequency
      values were observed in the SMB-treated groups (1 and 2g/kg doses) compared to
      the control animals. The Kruskal-Wallis test showed that the mean micronucleus
      frequencies in peripheral blood and bone marrow cells of mice treated with the
      highest dose of SMB (2g/kg) showed significant increases, when compared with
      controls, and a significant reduction in the ratio of polychromatic to
      normochromatic erythrocytes was also seen. No difference in results between sexes
      was observed. Our results show that high oral doses of SMB may pose a genotoxic
      risk.

PMID- 21185392
TI  - Mild stretch activates cPLA2 in alveolar type II epithelial cells independently
      through the MEK/ERK and PI3K pathways.
AB  - Alveolar epithelial type II cells (AT II) in which lung surfactant synthesis and
      secretion take place, are subjected to low magnitude stretch during normal
      breathing. The aim of the study was to explore the effect of mild stretch on
      phospholipase A(2) (PLA(2)) activation, an enzyme known to be involved in
      surfactant secretion. In A549 cells (a model of AT II cells), we showed, using a
      fluorometric assay, that stretch triggers an increase of total PLA(2) activity.
      Western blot experiments revealed that the cytosolic isoform cPLA(2) is rapidly
      phosphorylated under stretch, in addition to a modest increase in cPLA(2) mRNA
      levels. Treatment of A549 cells with selective inhibitors of the MEK/ERK pathway
      significantly attenuated the stretch-induced cPLA(2) phosphorylation. A strong
      interaction of cPLA(2) and pERK enzymes was demonstrated by immunoprecipitation.
      We also found that inhibition of PI3K pathway attenuated cPLA(2) activation after
      stretch, without affecting pERK levels. Our results suggest that low magnitude
      stretch can induce cPLA(2) phosphorylation through the MEK/ERK and PI3K-Akt
      pathways, independently.

PMID- 21185393
TI  - The male postabdomen of the "ancestral" archostematan beetle Tetraphalerus bruchi
      Heller, 1913 (Ommatidae) and its phylogenetic significance.
AB  - External and internal features of the male postabdomen of Tetraphalerus bruchi
      were examined with a broad spectrum of morphological techniques and are described
      in detail. The conditions found in males of Tetraphalerus are compared to those
      in other archostematan beetles and members of other coleopteran suborders. The
      far-reaching reduction of the sternite I, structural modifications of sternite
      II, the retracted condition of the terminal segments, and ventromedially fused
      apodemes arising from the anterior margin of tergite IX are likely autapomorphies
      of Coleoptera. The male postabdomen of Tetraphalerus is less derived than in most
      other groups of Coleoptera. The sclerotized elements are symmetrical. In contrast
      to earlier statements on the archostematan male genital apparatus a distinctly
      developed, sclerotized basal piece is present. The aedeagus is trilobed and all
      elements of the copulatory apparatus are distinct. The muscular equipment is
      simple and moderately developed. All muscles (except the transverse muscles 61
      and 62) occur pairwise and symmetrically. The distinct increase of the number of
      postabdominal muscles in representatives of the higher lineages of Coleoptera is
      likely linked with a torsion of the copulatory apparatus, which also results in
      asymmetries of the sclerotised parts. The testes of Tetraphalerus are long, multi
      coiled tubes like in other archostematans, Myxophaga (Torridincola) and Adephaga.
      The presence of a deep notch on the parameres is a synapomorphy of Tetraphalerus
      and Omma. Curved parameres, a shortened distal portion, and a distinctly
      shortened penis are potential synapomorphies of Omma rutherfordi and Omma
      mastersi. The large size of the sclerotized part of the phallobase ('basal
      piece') and the division of the sclerotization of sternum IX are potential ground
      plan autapomorphies of Archostemata, with secondary modification of the latter
      feature in Cupedidae. The reduced condition of the sclerotization of sternum VIII
      is an apomorphic condition which has likely evolved independently in
      Tetraphalerus and Paracupes. Further anatomical investigation of the male genital
      apparatus of Coleoptera and holometabolous insects in general is required for a
      reliable morphological and phylogenetic interpretation. Concerning the presence
      or absence of particular sclerotizations (e.g., 'basal piece' of phallobase)
      histological section series and Confocal Laser Scanning Microscopy can add more
      precise information to what can be observed using permanent preparations of
      macerated specimens.

PMID- 21185394
TI  - Kaposi's sarcoma presenting as a bulky tumor mass of the colon.

PMID- 21185395
TI  - Tracheobronchial remnants: a rare congenital anomaly.

PMID- 21185396
TI  - Gastric electrical stimulation improves outcomes of patients with gastroparesis
      for up to 10 years.
AB  - BACKGROUND & AIMS: We assessed the long-term clinical outcomes of gastric
      electrical stimulation (GES) therapy with Enterra (Enterra Therapy System;
      Medtronic, Minneapolis, MN) in a large cohort of patients with severe
      gastroparesis. METHODS: Gastroparesis patients (n=221; 142 diabetic, 48
      idiopathic, and 31 postsurgical) treated with Enterra (Medtronic) for 1-11 years
      were retrospectively assessed; 188 had follow-up visits and data were collected
      for at least 1 year (mean 56 months, range 12-131 months). Total symptom scores
      (TSSs), gastric emptying, nutritional status, weight, hospitalizations, use of
      prokinetic and/or antiemetic medications, levels of HbA1c levels (in diabetic
      patients), and adverse events were evaluated at the beginning of the study
      (baseline) and during the follow-up period. RESULTS: TSS, hospitalization days,
      and use of medications were significantly reduced among all patients (P<.05).
      More patients with diabetic (58%) and postsurgical gastroparesis (53%) had a
      greater than 50% reduction in TSS than those with idiopathic disease (48%;
      P=.32). Weight significantly increased among all groups, and 89% of J-tubes could
      be removed. At end of the follow-up period, all etiological groups had similar,
      abnormal delays in mean gastric retention. Thirteen patients (7%) had their
      devices removed because of infection at the pulse generator site. CONCLUSIONS:
      GES therapy significantly improved subjective and objective parameters in
      patients with severe gastroparesis; efficacy was sustained for up to 10 years and
      was accompanied by good safety and tolerance profiles. Patients with diabetic or
      postsurgical gastroparesis benefited more than those with idiopathic disease.

PMID- 21185397
TI  - Diagnostic yield improves with collection of 2 samples in fecal immunochemical
      test screening without affecting attendance.
AB  - BACKGROUND & AIMS: The fecal immunochemical test (FIT) is superior to the guaiac
      based fecal occult blood test in detecting neoplasia. There are not much data on
      the optimal number of FITs to perform. We conducted a population-based trial to
      determine attendance and diagnostic yield of 1- and 2-sample FIT screening.
      METHODS: The study included 2 randomly selected groups of subjects aged 50-74
      years (1-sample FIT, n=5007; 2-sample FIT, n=3197). The 2-sample group was
      instructed to collect fecal samples on 2 consecutive days. Subjects were referred
      for colonoscopy when at least 1 sample tested positive (>=50 ng hemoglobin/mL).
      RESULTS: Attendance was 61.5% in the 1-sample group (2979 of 4845; 95% confidence
      interval, 60.1%-62.9%) and 61.3% in the 2-sample group (1875 of 3061; 95%
      confidence interval, 59.6%-63.0%; P=.84). In the 1-sample group 8.1% tested
      positive, and in the 2-sample group 12.8% had at least 1 positive test outcome
      and 5.0% had 2 positive test outcomes (P<.05). When the mean from both test
      results in the 2-sample group was used, 10.1% had a positive test outcome
      (P<.05). The detection rates for advanced neoplasia were 3.1% in the 1-sample
      group, 4.1% in the 2-sample group with at least 1 positive test outcome, 2.5%
      when both test results were positive, and 3.7% among subjects with the mean from
      both test results being positive. CONCLUSIONS: There is no difference in
      attendance for subjects offered 1- or 2-sample FIT screening. The results allow
      for the development of efficient FIT screening strategies that can be adapted for
      local colonoscopy capacities, rather than varying the cut-off value in a 1-sample
      strategy.

PMID- 21185398
TI  - Management of hepatitis B.

PMID- 21185399
TI  - IL28B-genotype testing now and in the era of direct-acting antiviral agents.

PMID- 21185400
TI  - Inappropriate sinus tachycardia in a transplanted heart--further insights into
      pathogenesis.

PMID- 21185401
TI  - The impact of cardiac resynchronization therapy on the incidence of ventricular
      arrhythmias in mild heart failure.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) decreases mortality, improves
      functional status, and induces reverse left ventricular (LV) remodeling in
      selected populations. However, the effect of CRT on ventricular arrhythmias is
      controversial. This is particularly important among patients with mild heart
      failure (HF), in whom sudden death is a leading cause of mortality. OBJECTIVE:
      This study sought to assess the impact of CRT on ventricular arrhythmias in mild
      HF. METHODS: The REsynchronization reVErses Remodeling in Systolic left
      vEntricular dysfunction (REVERSE) study is a multicenter randomized, double-blind
      trial of CRT among patients with mild systolic HF. The time to first appropriate,
      treated ventricular tachycardia/ventricular fibrillation (VT/VF) episode or
      spontaneous sustained VT in cardiac resynchronization therapy plus defibrillation
      device (CRT-D) patients was compared between groups, as were predictors of VT/VF.
      RESULTS: The study randomized 508 patients who received CRT-D devices. There were
      no significant demographic differences between groups. There were no differences
      in VT/VF episodes or VT storm between groups. Specifically, in the CRT ON group,
      the estimated event rate was 18.7% at 2 years, compared with 21.9% in the CRT OFF
      group (hazard ratio 1.05, P = .84). However, among CRT ON patients, those with
      reverse remodeling had a reduced incidence of VT/VF compared with those without
      remodeling (5.6% vs. 16.3%, hazard ratio 0.31, P = .001). CONCLUSION: CRT for up
      to 2 years does not impact VT/VF in mild HF despite marked clinical and
      remodeling effects of pacing. This neutral effect may be attributable to
      competing antiarrhythmic effects of reverse remodeling and proarrhythmic effect
      of pacing. CLINICAL TRIAL REGISTRATION:
      http://www.clinicaltrials.gov/ct2/show/NCT00271154.

PMID- 21185402
TI  - Circadian pattern of life-threatening ventricular arrhythmia in patients with
      sleep-disordered breathing and implantable cardioverter-defibrillators.
AB  - BACKGROUND: Sleep-disordered breathing (SDB) has been associated with various
      benign cardiac arrhythmias occurring during sleep. OBJECTIVE: The purpose of this
      study was to demonstrate that SDB contributes to the development of life
      threatening ventricular arrhythmias in patients with an established arrhythmic
      substrate. METHODS: We prospectively studied the association between SDB and
      timing of life-threatening ventricular arrhythmic events in 45 patients with an
      implantable cardioverter-defibrillator (ICD). SDB was defined as an apnea
      hypopnea index (AHI) >10 events/hour based on an overnight sleep study. The
      primary outcome measure was appropriate ICD therapy, defined as antitachycardia
      pacing or shock for ventricular tachycardia or ventricular fibrillation during 1
      year follow-up. RESULTS: SDB was present in 26 (57.8%) patients. Appropriate ICD
      therapies were higher among patients with SDB (73% vs 47%, P = .02). Logistic
      regression identified SDB as a predictor of any appropriate ICD therapy (odds
      ratio 4.4, 95% confidence interval 1.4-15.3, P = .01). The risk for ventricular
      arrhythmias was higher in patients with SDB solely due to an increase in events
      occurring between midnight and 6 AM (odds ratio 5.6, 95% confidence interval 2.0
      15.6, P = .001) with no discernible effect on appropriate ICD therapy during
      nonsleeping hours (odds ratio 0.7, 95% confidence interval 0.2-2.3, P = .61).
      CONCLUSION: Patients with an ICD and SDB have a striking increase in the onset of
      life-threatening ventricular arrhythmic events during sleeping hours. These
      findings provide a rationale for SDB screening in patients with appropriate ICD
      therapy if device interrogation reveals a predominance of nocturnal onset of
      arrhythmias.

PMID- 21185403
TI  - Mapping of cardiac electrical activation with electromechanical wave imaging: an
      in silico-in vivo reciprocity study.
AB  - BACKGROUND: Electromechanical wave imaging (EWI) is an entirely noninvasive,
      ultrasound-based imaging method capable of mapping the electromechanical
      activation sequence of the ventricles in vivo. Given the broad accessibility of
      ultrasound scanners in the clinic, the application of EWI could constitute a
      flexible surrogate for the 3-dimensional electrical activation. OBJECTIVE: The
      purpose of this report is to reproduce the electromechanical wave (EW) using an
      anatomically realistic electromechanical model, and establish the capability of
      EWI to map the electrical activation sequence in vivo when pacing from different
      locations. METHODS: EWI was performed in 1 canine during pacing from 3 different
      sites. A high-resolution dynamic model of coupled cardiac electromechanics of the
      canine heart was used to predict the experimentally recorded electromechanical
      wave. The simulated 3-dimensional electrical activation sequence was then
      compared with the experimental EW. RESULTS: The electrical activation sequence
      and the EW were highly correlated for all pacing sites. The relationship between
      the electrical activation and the EW onset was found to be linear, with a slope
      of 1.01 to 1.17 for different pacing schemes and imaging angles. CONCLUSION: The
      accurate reproduction of the EW in simulations indicates that the model framework
      is capable of accurately representing the cardiac electromechanics and thus
      testing new hypotheses. The one-to-one correspondence between the electrical
      activation and the EW sequences indicates that EWI could be used to map the
      cardiac electrical activity. This opens the door for further exploration of the
      technique in assisting in the early detection, diagnosis, and treatment
      monitoring of rhythm dysfunction.

PMID- 21185404
TI  - CNS regeneration after chronic injury using a self-assembled nanomaterial and
      MEMRI for real-time in vivo monitoring.
AB  - To speed up the process of central nervous system (CNS) recovery after injury,
      the need for real-time measurement of axon regeneration in vivo is essential to
      assess the extent of injury, as well as the optimal timing and delivery of
      therapeutics and rehabilitation. It was necessary to develop a chronic animal
      model with an in vivo measurement technique to provide a real-time monitoring and
      feedback system. Using the framework of the 4 P's of CNS regeneration (Preserve,
      Permit, Promote and Plasticity) as a guide, combined with noninvasive manganese
      enhanced magnetic resonance imaging (MEMRI), we show a successful chronic injury
      model to measure CNS regeneration, combined with an in vivo measurement system to
      provide real-time feedback during every stage of the regeneration process. We
      also show that a chronic optic tract (OT) lesion is able to heal, and axons are
      able to regenerate, when treated with a self-assembling nanofiber peptide
      scaffold (SAPNS). FROM THE CLINICAL EDITOR: The authors of this study demonstrate
      the development of a chronic injury model to measure CNS regeneration, combined
      with an in vivo measurement system to provide real-time feedback during every
      stage of the regeneration process. In addition, they determined that chronic
      optic tract lesions are able to heal with axonal regeneration when treated with a
      self-assembling nanofiber peptide scaffold (SAPNS).

PMID- 21185405
TI  - The use and abuse of multiple outcomes in randomized controlled depression
      trials.
AB  - OBJECTIVE: Multiple outcomes are commonly analyzed in randomized trials.
      Interpretation of the results of trials with many outcomes is not always
      straightforward. We characterize the prevalence and factors associated with
      multiple outcomes in reports of clinical trials of depression, methods used to
      account for these outcomes, and concordance between published analyses and
      original protocol specifications. METHODS: A PubMed search for randomized
      controlled depression trials that included multiple outcomes published between
      January 2007 and October 2008 in 6 medical journals. Original study protocols
      were reviewed where available. Parallel data collection by 2 abstractors was used
      to determine trial registration information, the number of outcomes, and
      analytical method. RESULTS: Of the 55 included trials, nearly half of the papers
      reported more than 1 primary outcome, while almost all (90.9%, n = 50) reported
      more than 2 combined primary or secondary outcomes. Relatively few of the studies
      (5.8%, n = 3) adjusted for multiple outcomes. While most studies had published
      protocols in clinical trial registries (76.4%, n = 42), many did not specify
      outcomes in the protocol (n = 11) and a number had discrepancies with the
      published report. CONCLUSIONS: Multiple outcomes are prevalent in randomized
      controlled depression trials and appropriate statistical analyses to account for
      these methods are rarely used. Not all studies filed protocols, and there were
      discrepancies between these protocols and published reports. These issues
      complicate interpretability of trial results, and in some cases may lead to
      spurious conclusions. Promulgation of guidelines to improve analysis and
      reporting of multiple outcomes is warranted.

PMID- 21185406
TI  - B cells and immunosenescence: a focus on IgG+IgD-CD27- (DN) B cells in aged
      humans.
AB  - Immunosenescence contributes to the decreased ability of the elderly to control
      infectious diseases, which is also reflected in their generally poor response to
      new antigens and vaccination. It is known that the T cell branch of the immune
      system is impaired in the elderly mainly due to expansion of memory/effector
      cells that renders the immune system less able to respond to new antigens. B
      lymphocytes are also impaired in the elderly in terms of their response to new
      antigens. In this paper we review recent work on B cell immunosenescence focusing
      our attention on memory B cells and a subset of memory B cells (namely IgG(+)IgD(
      )CD27(-)) that we have demonstrated is increased in healthy elderly.

PMID- 21185407
TI  - Influence of serum protein and albumin addition on the structure and activity of
      an exogenous pulmonary surfactant.
AB  - The comparative analysis of the deleterious action of albumin and total serum
      proteins (SP) might help to understand the nature of the interaction surfactant-
      SP. This study evaluated the effects of serum proteins and albumin on bulk shear
      viscosity, surface tension, surface area reduction, and the ratio between the
      light and heavy subtypes of surfactant suspensions. Our results showed a
      correlation between the bulk viscosity and aggregation degree of surfactant
      suspensions. The addition of albumin or SP induced the transformation from the
      heavy to the light subtype, reducing the viscosity. SP caused disaggregation and
      inactivation, whereas albumin caused only disaggregation without loss of surface
      activity. When SP were removed, the heavy fraction obtained recovered its surface
      activity. We conclude that the disaggregation may not be the primary cause for
      the loss of surface activity. Surfactant inactivation by a serum component,
      different from albumin, would be probably due to a physical interaction, a
      phenomenon that is reversed when SP are removed.

PMID- 21185409
TI  - Mechanical characteristics of solid-freeform-fabricated porous calcium
      polyphosphate structures with oriented stacked layers.
AB  - This study addresses the mechanical properties of calcium polyphosphate (CPP)
      structures formed by stacked layers using a powder-based solid freeform
      fabrication (SFF) technique. The mechanical properties of the 35% porous
      structures were characterized by uniaxial compression testing for compressive
      strength determination and diametral compression testing to determine tensile
      strength. Fracture cleavage surfaces were analyzed using scanning electron
      microscopy. The effects of the fabrication process on the microarchitecture of
      the CPP samples were also investigated. Results suggest that the orientation of
      the stacked layers has a substantial influence on the mechanical behavior of the
      SFF-made CPP samples. The samples with layers stacked parallel to the mechanical
      compressive load are 48% stronger than those with the layers stacked
      perpendicular to the load. However, the samples with different stacking
      orientations are not significantly different in tensile strength. The observed
      anisotropic mechanical properties were analyzed based on the physical
      microstructural properties of the CPP structures.

PMID- 21185408
TI  - Assessment of growth factor treatment on fibrochondrocyte and chondrocyte co
      cultures for TMJ fibrocartilage engineering.
AB  - Treatments for patients suffering from severe temporomandibular joint (TMJ)
      dysfunction are limited, motivating the development of strategies for tissue
      regeneration. In this study, co-cultures of fibrochondrocytes (FCs) and articular
      chondrocytes (ACs) were seeded in agarose wells, and supplemented with growth
      factors, to engineer tissue with biomechanical properties and extracellular
      matrix composition similar to native TMJ fibrocartilage. In the first phase,
      growth factors were applied alone and in combination, in the presence or absence
      of serum, while in the second phase, the best overall treatment was applied at
      intermittent dosing. Continuous treatment of AC/FC co-cultures with TGF-beta1 in
      serum-free medium resulted in constructs with glycosaminoglycan/wet weight ratios
      (12.2%), instantaneous compressive moduli (790 kPa), relaxed compressive moduli
      (120 kPa) and Young's moduli (1.87 MPa) that overlap with native TMJ disc values.
      Among co-culture groups, TGF-beta1 treatment increased collagen deposition ~20%,
      compressive stiffness ~130% and Young's modulus ~170% relative to controls
      without growth factor. Serum supplementation, though generally detrimental to
      functional properties, was identified as a powerful mediator of FC construct
      morphology. Finally, both intermittent and continuous TGF-beta1 treatment showed
      positive effects, though continuous treatment resulted in greater enhancement of
      construct functional properties. This work proposes a strategy for regeneration
      of TMJ fibrocartilage and its future application will be realized through
      translation of these findings to clinically viable cell sources.

PMID- 21185410
TI  - Structural and spectroscopic characterization of a series of potassium- and/or
      sodium-substituted beta-tricalcium phosphate.
AB  - In this paper, we report X-ray diffraction investigations as well as Raman and
      solid-state (31)P and (23)Na magic angle spinning nuclear magnetic resonance
      (NMR) characterization of three series of calcium orthophosphates. The general
      formulae of the studied compounds are Ca(10.5-x/2)M(x)(PO(4))(7), where M=K or Na
      and x=0, 0.25, 0.50, 0.75, 1.0; and Ca(10)K(x)Na(1-x)(PO(4))(7), where x=0, 0.25,
      0.5, 0.75, 1.0. These calcium orthophosphates are found to be isostructural with
      beta-tricalcium phosphate (beta-TCP, Ca(3)(PO(4))(2)) with the substitution of
      some calcium sites by potassium and/or sodium cations. The unit cell parameters
      vary continuously with the level of substitution, a characteristic of these solid
      solutions. The Raman spectra show the different vibrational bands of the
      phosphate groups PO(4), while the NMR chemical shifts are sensitive to the non
      equivalent phosphorus and sodium ions present in these substituted samples. As
      both Raman and NMR spectroscopies are local probes, they offer tools to
      distinguish between these different phosphorus and phosphate groups, according to
      their structural site and local environment, especially the type of cation
      substituent. A convenient decomposition of the Raman and NMR spectra into
      Gaussian-Lorentzian components leads us to propose an assignment of the main
      observed bands of these substituted beta-TCPs.

PMID- 21185411
TI  - Bioconversion of Saccharum spontaneum (wild sugarcane) hemicellulosic hydrolysate
      into ethanol by mono and co-cultures of Pichia stipitis NCIM3498 and
      thermotolerant Saccharomyces cerevisiae-VS3.
AB  - The lignocellulosic biomass is a low-cost renewable resource for eco-benign
      liquid fuel 'ethanol'. To resolve the hydrolysis of mixed sugars in
      lignocellulosic substrate Saccharum spontaneum, the microbial co-cultures of
      Pichia stipitis NCIM 3498 and thermotolerant Saccharomyces cerevisiae-VS(3) were
      analyzed for efficient bioconversion of mixed sugars into ethanol. Among the
      hydrolysis conditions, the acid hydrolysis released maximum sugars along with
      furans, phenolics and acetic acid. The acidic hydrolysate was detoxified and
      fermented by monocultures of P. stipitis NCIM3498 (P.S.) and thermotolerant S.
      cerevisiae VS(3) (S.C.), and co-culture of P.S. (7.5 mL) and S.C. (2.5 mL).
      Before the fermentation of hemicellulose acid hydrolysate, both the monocultures
      (P.S. and S.C.), and varying ratios of P.S. and S.C. microorganisms in co
      cultures #1, #2 and #3 were grown on simulated synthetic medium. The ethanol
      yield from monocultures of P.S. (0.44 +/- 0.021 g/g), S.C. (0.22 +/- 0.01 g/g)
      and co-culture #3 (0.49 +/- 0.02 g/g) revealed unique characteristics of each
      mono and co-culture technology. The fermentation of hemicellulose acid
      hydrolysate with monocultures of P.S., S.C. and co-culture #3 produced 12.08 +/-
      0.72 g/L, 1.40 +/- 0.07 g/L, and 15.0 +/- -0.92 g/L ethanol, respectively.

PMID- 21185412
TI  - General analysis of mathematical models for bone remodeling.
AB  - Bone remodeling is regulated by pathways controlling the interplay of osteoblasts
      and osteoclasts. In this work, we apply the method of generalized modeling to
      systematically analyse a large class of models of bone remodeling. Our analysis
      shows that osteoblast precursors can play an important role in the regulation of
      bone remodeling. Further, we find that the parameter regime most likely realized
      in nature lies close to bifurcation lines, marking qualitative changes in the
      dynamics. Although proximity to a bifurcation facilitates adaptive responses to
      changing external conditions, it entails the danger of losing dynamical
      stability. Some evidence implicates such dynamical transitions as a potential
      mechanism leading to forms of Paget's disease.

PMID- 21185413
TI  - Increased serum adiponectin concentrations in amenorrheic physically active women
      are associated with impaired bone health but not with estrogen exposure.
AB  - BACKGROUND: The role of adiponectin in mediating gonadal status and bone health
      in weight-stable healthy adult female athletes with secondary amenorrhea has not
      yet been described. METHODS: Using a prospective observational study, age-matched
      premenopausal women were studied, including 1) sedentary ovulatory women (SedOv;
      n=10), 2) exercising ovulatory women (ExOv; n=15), and 3) exercising amenorrheic
      women (ExAmen; n=9). Primary outcome measures included serum total adiponectin
      and daily urinary estrogen (E1G) levels, expressed as area under the curve (AUC),
      body fat distribution, and bone mineral density (BMD). Serum leptin, ghrelin,
      total triiodothyronine (TT3), insulin, and resting energy expenditure (REE) were
      also determined. RESULTS: The women in this study did not differ in age (25.3+/
      1.4 years; mean +/- SEM), height (164+/-1 cm), weight (57.7+/-1.0 kg) and BMI
      (21.5+/-0.4 kg/m(2)). Exercising women had a higher fat free mass (FFM), lower
      fat mass (FM) and lower serum leptin concentrations (p<0.05) compared to
      sedentary women. Adiponectin and ghrelin levels were higher (p<0.05), and TT3
      (p=0.019), urinary E1G AUC (p=0.002) lower in ExAmen compared with ExOv and
      SedOv. Total and L1-L4 BMD were lower (p<0.05) in ExAmen compared with ExOv.
      Stepwise linear regression identified trunkal FM as the strongest predictor of
      log adiponectin adjusted for FM (F=23.54, p<0.001). L1-L4 BMD was predicted by
      log adiponectin and E1G AUC (F=9.856, p=0.045). Total BMD was predicted by log
      adiponectin (F=7.948, p=0.009). TT3 was the strongest predictor of E1G AUC
      (F=9.885, p=0.004). CONCLUSIONS: Hypoestrogenic adult female athletes with
      secondary amenorrhea demonstrate elevated circulating adiponectin relative to FM
      in association with impaired bone health. Estrogen exposure was predicted by TT3,
      but not adiponectin. These findings suggest that nutritionally regulated hormones
      may mediate gonadal status, and that adiponectin and estrogen, either
      independently or in combination, may mediate bone health in adult amenorrheic
      physically active women.

PMID- 21185414
TI  - Vulnerability of healthy vertebrae in patients with and without previous
      vertebral fracture.
AB  - Vertebral deformities are associated with a marked increase in morbidity,
      mortality, and burden in terms of sanitary expenditures. Patients with vertebral
      fractures have a negative impact in their health, less quality of life, and loss
      of functional capacity and independence. The purpose of this study was to explore
      the vulnerability of healthy vertebrae in patients who have sustained already a
      compression fracture and in patients who do not have prevalent fractures in the
      thoracic spine; and to explore the association of the deformity in healthy
      vertebrae with different variables, such as bone mineral density (BMD), body mass
      index, age, loss of height, presence of clinical kyphosis, history of other
      osteoporotic fractures, and falls occurring during the last year. Clinical data
      and complementary studies from 175 postmenopausal outpatients were analyzed.
      These women (age: 69.7+/-11.1 years) had not received any treatment for
      osteoporosis. Anteroposterior and lateral radiographs of the thoracic spine and
      bone densitometry of the hip were obtained; morphometry was performed in 1575
      thoracic vertebrae from T4 to T12. The angle of wedging of each vertebral body
      was calculated using a trigonometric formula. Then, the sum of wedge angles of
      vertebral bodies (SWA) was determined, and Cobb angle was measured. In patients
      with vertebral fractures, after excluding the angles of fractured vertebral
      bodies, the mean wedge angle of the remaining vertebrae (MWAhealthy) was
      calculated. The same procedure was followed in patients without vertebral
      fractures. MWAhealthy was considered as an indicator of the structural
      vulnerability of non-fractured vertebrae. Patients with prevalent fractures had
      lower BMD, wider Cobb angle, and higher sum of wedge angles than patients without
      vertebral fractures. The proportion of patients with accentuation of clinical
      kyphosis was higher in the group with prevalent vertebral fractures. A highly
      significant difference was found in the MWAhealthy, which was higher in patients
      with prevalent fractures (4.1+/-1.3 degrees  vs. 3.0+/-1.1 degrees ; p<0.001).
      Patients showing vertebral fractures had 7.1+/-4.2 cm height loss in average,
      significantly superior than that found among non-fractured women (3.6+/-3.2 cm;
      p<0.01). In multivariate analysis, the increase of MWAhealthy was associated with
      advancing age (p<0.02), lower femoral neck BMD (p<0.005), presence of clinical
      kyphosis (p<0.01) and vertebral fractures (p<0.02). This study presents evidence
      that a series of factors independently influence the increase in wedging
      deformity of vertebral bodies that are not fractured yet. These factors could
      contribute to an increased vulnerability of the vertebrae, making them more
      susceptible to fracture.

PMID- 21185415
TI  - Matrix metalloproteinases in osteoclasts of ontogenetic and regenerating
      zebrafish scales.
AB  - Matrix metalloproteinases (MMPs) are key enzymes in the turnover of extracellular
      matrix in health, disease, development and regeneration. We have studied
      zebrafish scale regeneration to ascertain the role of MMP-2 and MMP-9 in these
      processes. Scales were plucked from the surface of anaesthetised adult male
      zebrafish, and the scales that regenerated in the scale pocket were recovered at
      various time points after plucking. Analyses consisted of (i) mmp-9 in situ
      hybridisation; (ii) MMP-9+TRAcP double-staining; (iii) qRT-PCR for mmp-2 and mmp
      9; (iv) zymography for gelatinolytic activity and (v) a hydroxyproline assay. We
      found that mmp-9 positive cells were confined to the episquamal side of the
      scales. Ontogenetic scales had irregular clusters of mono- and multinucleated mmp
      9 expressing cells along their lateral margins and radii. During regeneration,
      mmp-9 positive cells were seen on the scale plate, but not along the lateral
      margins. Double staining for TRAcP and MMP-9 revealed the osteoclastic nature of
      these cells. During early scale regeneration, mmp-2 and mmp-9 transcripts
      increased in abundance in the scale, enzymatic MMP activity increased and
      collagen degradation was detected by means of hydroxyproline measurements. Near
      the end of regeneration, all of these parameters returned to the basal values
      seen in ontogenetic scales. These findings suggest that MMPs play an important
      role in remodelling of the scale plate during regeneration, and that this
      function resides in mononucleated and multinucleated osteoclasts which co-express
      TRAcP and mmp-9. Our findings suggest that the fish scale regeneration model may
      be a useful system in which to study the cells and mechanisms responsible for
      regeneration, development and skeletal remodelling.

PMID- 21185417
TI  - Meta-analysis: risk of fractures with acid-suppressing medication.
AB  - AIMS: Recent studies have suggested an increased risk of fractures with proton
      pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs). We planned
      to perform a meta-analysis of fractures in patients taking PPIs and H2RAs.
      METHODS: We searched MEDLINE and EMBASE in September 2010 for observational
      studies reporting on the risk of fractures with acid-suppressing medication (PPIs
      and H2RA). We also checked the references lists of included studies and
      regulatory authority websites for additional data. We performed random effects
      meta-analysis of odds ratios (OR) according to fracture type and conducted
      subgroup analyses by duration of exposure. Heterogeneity was assessed using the
      I(2) statistic. RESULTS: Our review included 12 studies covering 1,521,062
      patients. Pooled analysis of PPI use showed significant risk for spine fractures
      (4 studies, OR 1.50, 95% CI 1.32-1.72, p<0.001, I(2)=0%) but this was not
      significant for H2RA (3 studies, OR 1.05, 95% CI 0.92-1.19, p=0.50, I(2)=0%).
      Similarly for hip fractures, there was a significant risk of fractures with PPIs
      (10 studies, OR 1.23, 95% CI 1.11-1.36, p<0.001, I(2)=72%), but not for H2RAs (9
      studies, OR 1.12, 95% CI 0.99-1.27, p=0.06, I(2)=75%), respectively). Analysis of
      fractures overall (based on all 12 studies covering a mixture of fracture types)
      yielded an OR of 1.20 (95% CI 1.11-1.30, p<0.001, I(2)=78%) for PPIs, and OR of
      1.08 (95% CI 1.00-1.18, p=0.06, I(2)=82%) for H2RA. However, aside from the risk
      of spine fractures, all the other analyses were limited by substantial
      heterogeneity. One study that reported on a direct comparison between acid
      suppressing medications found an increased risk with PPIs vs. H2RA for hip
      fractures, OR 1.34 (95% CI 1.14-1.38). CONCLUSION: There is some evidence for a
      modest association between PPI use and risk of fractures, which was not seen with
      H2RA exposure. The association is most consistent for spine fractures, while
      there is substantial heterogeneity in the magnitude of risk for other fractures.
      Clinicians who are concerned about patients with high fracture risk may wish to
      consider the option of H2RAs instead of PPIs.

PMID- 21185416
TI  - Increasing duration of type 1 diabetes perturbs the strength-structure
      relationship and increases brittleness of bone.
AB  - Type 1 diabetes (T1DM) increases the likelihood of a fracture. Despite serious
      complications in the healing of fractures among those with diabetes, the
      underlying causes are not delineated for the effect of diabetes on the fracture
      resistance of bone. Therefore, in a mouse model of T1DM, we have investigated the
      possibility that a prolonged state of diabetes perturbs the relationship between
      bone strength and structure (i.e., affects tissue properties). At 10, 15, and 18
      weeks following injection of streptozotocin to induce diabetes, diabetic male
      mice and age-matched controls were examined for measures of skeletal integrity.
      We assessed 1) the moment of inertia (I(MIN)) of the cortical bone within
      diaphysis, trabecular bone architecture of the metaphysis, and mineralization
      density of the tissue (TMD) for each compartment of the femur by micro-computed
      tomography and 2) biomechanical properties by three-point bending test (femur)
      and nanoindentation (tibia). In the metaphysis, a significant decrease in
      trabecular bone volume fraction and trabecular TMD was apparent after 10 weeks of
      diabetes. For cortical bone, type 1 diabetes was associated with decreased
      cortical TMD, I(MIN), rigidity, and peak moment as well as a lack of normal age
      related increases in the biomechanical properties. However, there were only
      modest differences in material properties between diabetic and normal mice at
      both whole bone and tissue-levels. As the duration of diabetes increased, bone
      toughness decreased relative to control. If the sole effect of diabetes on bone
      strength was due to a reduction in bone size, then I(MIN) would be the only
      significant variable explaining the variance in the maximum moment. However,
      general linear modeling found that the relationship between peak moment and
      I(MIN) depended on whether the bone was from a diabetic mouse and the duration of
      diabetes. Thus, these findings suggest that the elevated fracture risk among
      diabetics is impacted by complex changes in tissue properties that ultimately
      reduce the fracture resistance of bone.

PMID- 21185418
TI  - Estimation of bone mineral density in children from diagnostic CT images: a
      comparison of methods with and without an internal calibration standard.
AB  - We investigated the feasibility and potential limitations of estimating bone
      mineral density (BMD) from standard diagnostic computed tomography (dCT). We
      analyzed three sets of BMD measurements for L1 and L2, each performed by a novice
      and an expert, for intra- and interobserver variance (n=43 studies from 38
      patients; median age, 13.2 years) using one BMD quantification system with
      (conventional quantitative computed tomography (QCT)) and two without (QCT and
      dCT) an external calibration phantom. Using ANOVA model, means of three sets of
      BMD measurements analyzed by the expert differed by 2.5mg/cm(2); for the novice,
      by less than 1mg/cm(2). Variation of measurement differences was less for the
      expert. Mean intra- and interobserver absolute standardized differences (ASD)
      were 1.77% and 1.8%, respectively. The mean ASD between phantom and phantom-less
      methods of QCT studies were 3.3%; mean ASD of phantom QCT versus phantom-less dCT
      was 14.3%. Regression modeling suggested compensation for sources of dCT BMD
      measurement bias can reduce the mean ASD of phantom QCT versus phantom-less dCT
      to 6.5%. Thus, phantom-less QCT of dCT adds clinically useful BMD information not
      typically attained from dCT, thereby augmenting patient care and presenting
      important possibilities for research without need for additional study.

PMID- 21185419
TI  - Serum osteocalcin level is positively associated with insulin sensitivity and
      secretion in patients with type 2 diabetes.
AB  - OBJECTIVE: Bone is being recognized as an endocrine organ. Although previous
      animal studies showed that osteocalcin stimulated the expression of insulin in
      islets and of adiponectin in adipocytes with increased insulin secretion and
      sensitivity, the associations of serum osteocalcin with those parameters remain
      unclear in humans. METHODS: In this cross-sectional study, we employed 101
      postmenopausal women and 152 men with type 2 diabetes, who have not taken drugs
      for diabetes or osteoporosis. We also examined 75 g oral glucose tolerance test
      (OGTT) in 18 postmenopausal women and 20 men who visited our clinic for medical
      check-up for diabetes. RESULTS: In both postmenopausal women and men, multiple
      regression analysis adjusted for age, body mass index, and serum creatinine
      showed that serum osteocalcin level was significantly and negatively associated
      with fasting plasma glucose, HbA(1c), %Trunk fat, and homeostasis model
      assessment (HOMA) for insulin resistance (p<0.05), and positively with HOMA for
      beta-cell function (p<0.05). In addition, significant positive association of
      serum osteocalcin level with serum adiponectin level was found in postmenopausal
      women (p<0.05), but not in men. In the OGTT examinations, subjects were divided
      into tertiles by their serum osteocalcin levels in each gender. Postmenopausal
      women in the lowest tertile showed hyperglycemia and hyperinsulinemia compared to
      those in the highest tertile after oral glucose loading (p<0.05). Men in the
      lowest tertile also exhibited hyperinsulinemia (p<0.05), while hyperglycemia was
      not found. CONCLUSION: These findings indicate that serum osteocalcin level is
      positively associated with insulin sensitivity and secretion in Japanese patients
      with type 2 diabetes.

PMID- 21185420
TI  - An unusual case of a "hepatic" tumor.

PMID- 21185421
TI  - A rare esophageal disorder.

PMID- 21185422
TI  - 2009 H1N1 influenza vaccines in pregnant women: the French Pharmacovigilance
      survey.

PMID- 21185423
TI  - Immunogenicity and tolerability of an inactivated and adjuvanted pandemic H1N1
      influenza vaccine, in HIV-1-infected patients.
AB  - We evaluated the efficacy and tolerability of a single dose of the split virion
      AS03-adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in 84 HIV-1
      infected individuals. Antibody titers were determined by hemagglutination
      inhibition assay and by microneutralization. Vaccine was well tolerated. At 21
      days post vaccination, 56 (67%) patients had seroconverted. There was no
      correlation between baseline CD4 cell count (p=0.539) or HIV viral load (p=0.381)
      and immune response. Other vaccine strategies should be evaluated in this HIV
      population, to improve response rates.

PMID- 21185424
TI  - Determinants of influenza vaccine purchasing decision in the US: a conjoint
      analysis.
AB  - We explore the determinants of influenza vaccine purchasing decision in the US
      via a nationwide survey of 251 medical office managers and physicians on
      preferences for seven vaccine presentation attributes: price, presence of
      thimerosal, contamination risk, storage space requirement, number of preparation
      steps, dosing errors and speed. The findings show that thimerosal, contamination
      risk, and dosing errors were the most important attributes. For pediatricians,
      thimerosal's absence was shown to be the most valuable attribute. Participants
      would be willing to spend the following additional amounts per dose of influenza
      vaccine to acquire products as follows: $5.06 for the absence of thimerosal,
      $5.23 for a lower contamination risk, $4.94 for lower chance of dosing errors.
      They would pay $1.08 more for influenza vaccines that were faster to administer,
      $1.27 more for vaccines that were easier to store, and $1.76 more for vaccines
      that had fewer steps to administer.

PMID- 21185425
TI  - [Formalized expert recommendations. Screening and management of bipolar
      disorders].

PMID- 21185426
TI  - [Screening and management of bipolar disorders: methodology].

PMID- 21185427
TI  - [Screening and management of bipolar disorders: results].

PMID- 21185428
TI  - Methods in Enzymology. Research on Nitrification and Related Processes, Part A.
      Preface.

PMID- 21185429
TI  - Modeling the role of nitrification in open ocean productivity and the nitrogen
      cycle.
AB  - The ocean is an important component of the global carbon cycle, and currently
      serves as the principal sink for anthropogenic CO(2) from the atmosphere. A key
      role in the natural oceanic carbon cycle is played by the plankton ecosystem,
      which acts to elevate the storage capacity of the ocean, but it is believed that
      this will experience change in the future in response to anthropogenic forcing.
      One of the approaches used to understand and forecast the oceanic carbon cycle is
      ecosystem modeling, and this is typically grounded on the nitrogen cycle because
      of the strong regulatory role this element plays in biological productivity.
      Nitrification is one of the central processes in the oceanic nitrogen cycle, one
      whose role may change in the future, but also one with a particular relevance to
      observational efforts to quantify the biological carbon cycle. Here, we describe
      and summarize current efforts to model nitrification in pelagic open ocean
      ecosystems, and look forward to future avenues for progress.

PMID- 21185430
TI  - Continuous cultivation and thermodynamic aspects of niche definition in the
      nitrogen cycle.
AB  - The study of model organisms in pure culture has provided detailed information
      about the physiology and biochemistry of nitrification and related processes.
      Metagenomic sequencing of environmental samples is providing information to what
      extent this understanding also applies to natural microbial communities. Here, we
      outline a conceptual and experimental strategy that links these two approaches.
      It consists of the mathematical modeling of nitrification and related processes.
      The model predictions are subsequently validated experimentally by the study of
      natural microbial communities in continuous cultures under precisely defined
      environmental conditions. Combined with calorimetry and metagenomic monitoring
      this form of "experimental metagenomics" enables the answering of current
      questions in the ecology of the nitrogen cycle.

PMID- 21185431
TI  - Isolation, cultivation, and characterization of ammonia-oxidizing bacteria and
      archaea adapted to low ammonium concentrations.
AB  - Ammonia-oxidizing microorganisms (AOM) generate their energy by the oxidation of
      ammonia (NH(3)) to nitrite (NO(2)(-)). This process can be carried out by ammonia
      oxidizing bacteria (AOB) as well as by the recently discovered ammonia-oxidizing
      archaea (AOA). In the past, AOB were enriched in batch cultures, often in the
      presence of rather high concentrations of NH(4)(+). Here, we describe methods to
      enrich, isolate, and investigate the basic physiology of AOB and AOA with
      emphasis on those that are adapted to low NH(4)(+) concentrations. The methods
      described include enrichment of AOA and AOB in batch cultures and of AOB in
      continuous cultures, the isolation of AOA by serial dilution and AOB by pour
      plates or dilution to extinction, and techniques to determine growth and activity
      of the AOA and AOB. Finally, we incorporated a section with Appendix about the
      identification of AOA and AOB as well as the measurement of the different
      inorganic nitrogen species.

PMID- 21185432
TI  - Cultivation, detection, and ecophysiology of anaerobic ammonium-oxidizing
      bacteria.
AB  - Anaerobic ammonium-oxidizing (anammox) bacteria oxidize ammonium with nitrite
      under anoxic conditions. The anammox process is currently used to remove ammonium
      from wastewater and contributes significantly to the loss of fixed nitrogen from
      the oceans. In this chapter, we focus on the ecophysiology of anammox bacteria
      and describe new methodologies to grow these microorganisms. Now, it is possible
      to enrich anammox bacteria up to 95% with a membrane bioreactor that removes
      forces of selection for fast settling aggregates and facilitates the growth of
      planktonic cells. The biomass from this system has a high anaerobic ammonium
      oxidation rate (50 fmol NH(4)(+) . cell(-1) day(-1)) and is suitable for many
      ecophysiological and molecular experiments. A high throughput Percoll density
      gradient centrifugation protocol may be applied on this biomass for further
      enrichment (>99.5%) of anammox bacteria. Furthermore, we provide an up-to-date
      list of commonly used primers and introduce protocols for quantification and
      detection of functional genes of anammox bacteria in their natural environment.

PMID- 21185433
TI  - Cultivation, growth physiology, and chemotaxonomy of nitrite-oxidizing bacteria.
AB  - Lithoautotrophic nitrite-oxidizing bacteria (NOB) are known as fastidious
      microorganisms, which are hard to maintain and not many groups are trained to
      keep them in culture. They convert nitrite stoichiometrically to nitrate and
      growth is slow due to the poor energy balance. NOB are comprised of five genera,
      which are scattered among the phylogenetic tree. Because NOB proliferate in a
      broad range of environmental conditions (terrestrial, marine, acidic) and have
      diverse lifestyles (lithoautotrophic, mixotrophic, and heterotrophic), variation
      in media composition is necessary to match their individual growth requirements
      in the laboratory. From Nitrobacter and Nitrococcus relatively high cell amounts
      can be achieved by consumption of high nitrite concentrations, whereas
      accumulation of cells belonging to Nitrospira, Nitrospina, or the new candidate
      genus Nitrotoga needs prolonged feeding procedures. Isolation is possible for
      planktonic cells by dilution series or plating techniques, but gets complicated
      for strains with a tendency to develop microcolonies like Nitrospira.
      Physiological experiments including determination of the temperature or pH
      optimum can be conducted with active laboratory cultures of NOB, but the
      attainment of reference values like cell protein content or cell numbers might be
      hard to realize due to the formation of flocs and the low cell density.
      Monitoring of laboratory enrichments is necessary especially if several species
      or genera coexist within the same culture and due to population shifts over time.
      Chemotaxonomy is a valuable method to identify and quantify NOB in biofilms and
      pure cultures alike, since fatty acid profiles reflect their phylogenetic
      heterogeneity. This chapter focusses on methods to enrich, isolate, and
      characterize NOB by various cultivation-based techniques.

PMID- 21185434
TI  - Surveying N2O-producing pathways in bacteria.
AB  - Nitrous oxide (N(2)O) is produced by bacteria as an intermediate of both
      dissimilatory and detoxification pathways under a range of oxygen levels,
      although the majority of N(2)O is released in suboxic to anoxic environments.
      N(2)O production under physiologically relevant conditions appears to require the
      reduction of nitric oxide (NO) produced from the oxidation of hydroxylamine
      (nitrification), reduction of nitrite (denitrification), or by host cells of
      pathogenic bacteria. In a single bacterial isolate, N(2)O-producing pathways can
      be complex, overlapping, involve multiple enzymes with the same function, and
      require multiple layers of regulatory machinery. This overview discusses how to
      identify known N(2)O-producing inventory and regulatory sequences within
      bacterial genome sequences and basic physiological approaches for investigating
      the function of that inventory. A multitude of review articles have been
      published on individual enzymes, pathways, regulation, and environmental
      significance of N(2)O-production encompassing a large diversity of bacterial
      isolates. The combination of next-generation deep sequencing platforms, emerging
      proteomics technologies, and basic microbial physiology can be used to expand
      what is known about N(2)O-producing pathways in individual bacterial species to
      discover novel inventory and unifying features of pathways. A combination of
      approaches is required to understand and generalize the function and control of
      N(2)O production across a range of temporal and spatial scales within natural and
      host environments.

PMID- 21185435
TI  - Stable isotope probing with 18O-water to investigate growth and mortality of
      ammonia oxidizing bacteria and archaea in soil.
AB  - Ammonia oxidizing bacteria (AOB) and archaea oxidize ammonia to nitrite, the
      first and rate-limiting step in the important ecosystem process of nitrification.
      Growth and mortality of ammonia oxidizers in soil are difficult to quantify but
      accurate measurements would offer important insights into how environmental
      parameters regulate the population dynamics of these organisms. Stable isotope
      probing (SIP) is a recently developed technique that can identify microorganisms
      that assimilate labeled substrates and can be adapted to quantify the growth of
      organisms in soil. Here, we describe the use of SIP with (18)O-water to
      investigate the growth and mortality of ammonia oxidizers in a soil taken from a
      ponderosa pine forest in northern Arizona, USA. Addition of ammonia to soil
      stimulated the growth of AOB but not ammonia oxidizing archaea (AOA). The
      mortality of AOA was increased upon addition of ammonia to soil; however, the
      variance in these measurements was high. The mortality of AOB, in contrast, was
      not impacted by addition of ammonia to soil. The results suggest that increased
      ammonia availability in soil favors AOB over AOA.

PMID- 21185436
TI  - Measuring nitrification, denitrification, and related biomarkers in terrestrial
      geothermal ecosystems.
AB  - Research on the nitrogen biogeochemical cycle in terrestrial geothermal
      ecosystems has recently been energized by the discovery of thermophilic ammonia
      oxidizing archaea (AOA). This chapter describes methods that have been used for
      measuring nitrification and denitrification in hot spring environments, including
      isotope pool dilution and tracer approaches, and the acetylene block approach.
      The chapter also summarizes qualitative and quantitative methods for measurement
      of functional and phylogenetic biomarkers of thermophiles potentially involved in
      these processes.

PMID- 21185437
TI  - Determining the distribution of marine and coastal ammonia-oxidizing archaea and
      bacteria using a quantitative approach.
AB  - The oxidation of ammonia to nitrite is the first and often rate-limiting step in
      nitrification and plays an important role in both nitrogen and carbon cycling.
      This process is carried out by two distinct groups of microorganisms: ammonia
      oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB). This chapter
      describes methods for measuring the abundance of AOA and AOB using ammonia
      monooxygenase subunit A (amoA) genes, with a particular emphasis on marine and
      coastal systems. We also describe quantitative measures designed to target two
      specific clades of marine AOA: the "shallow" (group A) and "deep" (group B) water
      column AOA.

PMID- 21185438
TI  - 15N-labeling experiments to dissect the contributions of heterotrophic
      denitrification and anammox to nitrogen removal in the OMZ waters of the ocean.
AB  - In recent years, (15)N-labeling experiments have become a powerful tool
      investigating rates and regulations of microbially mediated nitrogen loss
      processes in the ocean. This chapter introduces the theoretical and practical
      aspects of (15)N-labeling experiments to dissect the contribution of
      denitrification and anammox to nitrogen removal in oxygen minimum zones (OMZs).
      We provide a detailed description of the preparation and realization of the
      experiments on board. Subsequent measurements of N(2) isotopes using gas
      chromatography mass spectrometry as well as processing of data and calculation of
      anammox and denitrification rates are explained. Important supplementary
      measurements are specified, such as the measurement of nanomolar concentrations
      of ammonium, nitrite, and nitrate. Nutrient profiles and (15)N-experiments from
      the Peruvian OMZ are presented and discussed as an example.

PMID- 21185439
TI  - Assessment of nitrogen and oxygen isotopic fractionation during nitrification and
      its expression in the marine environment.
AB  - Nitrification is a microbially-catalyzed process whereby ammonia (NH(3)) is
      oxidized to nitrite (NO(2)(-)) and subsequently to nitrate (NO(3)(-)). It is also
      responsible for production of nitrous oxide (N(2)O), a climatically important
      greenhouse gas. Because the microbes responsible for nitrification are primarily
      autotrophic, nitrification provides a unique link between the carbon and nitrogen
      cycles. Nitrogen and oxygen stable isotope ratios have provided insights into
      where nitrification contributes to the availability of NO(2)(-) and NO(3)(-), and
      where it constitutes a significant source of N(2)O. This chapter describes
      methods for determining kinetic isotope effects involved with ammonia oxidation
      and nitrite oxidation, the two independent steps in the nitrification process,
      and their expression in the marine environment. It also outlines some remaining
      questions and issues related to isotopic fractionation during nitrification.

PMID- 21185440
TI  - Identification of diazotrophic microorganisms in marine sediment via fluorescence
      in situ hybridization coupled to nanoscale secondary ion mass spectrometry (FISH
      NanoSIMS).
AB  - Growing appreciation for the biogeochemical significance of uncultured
      microorganisms is changing the focus of environmental microbiology. Techniques
      designed to investigate microbial metabolism in situ are increasingly popular,
      from mRNA-targeted fluorescence in situ hybridization (FISH) to the "-omics"
      revolution, including metagenomics, transcriptomics, and proteomics. Recently,
      the coupling of FISH with nanometer-scale secondary ion mass spectrometry
      (NanoSIMS) has taken this movement in a new direction, allowing single-cell
      metabolic analysis of uncultured microbial phylogenic groups. The main advantage
      of FISH-NanoSIMS over previous noncultivation-based techniques to probe
      metabolism is its ability to directly link 16S rRNA phylogenetic identity to
      metabolic function. In the following chapter, we describe the procedures
      necessary to identify nitrogen-fixing microbes within marine sediment via FISH
      NanoSIMS, using our work on nitrogen fixation by uncultured deep-sea methane
      consuming archaea as a case study.

PMID- 21185441
TI  - Measurement and distribution of nitrification rates in the oceans.
AB  - Nitrification is the process that converts ammonium to nitrate and thus links the
      regeneration of organic nitrogen to fixed nitrogen loss by denitrification. The
      first step, oxidation of ammonia to nitrite, is performed by a phylogenetically
      restricted group of proteobacteria (ammonia-oxidizing bacteria, AOB) and
      Crenarchaea (ammonia-oxidizing archaea, AOA). The second step is restricted to
      nitrite-oxidizing bacteria (NOB) as far as currently known. All three groups are
      assumed to be autotrophic and obligately aerobic, but the true extent of
      autotrophy and potential anaerobic pathways in these organisms is currently under
      investigation. Here, we describe methods for the measurement of nitrification
      rates in the marine environment, with a focus on seawater systems and stable
      isotopic tracer methods. The methods vary in analytical requirements but share
      the need for incubations, which must be optimized for different environments with
      different substrate concentrations. Recent advances in mass spectrometry now make
      it possible to minimize incubation artifacts and to achieve greatly improved
      sensitivity.

PMID- 21185442
TI  - Construction of STOX oxygen sensors and their application for determination of O2
      concentrations in oxygen minimum zones.
AB  - Until recently, it has not been possible to measure O(2) concentrations in oxygen
      minimum zones (OMZs) with sufficient detection limits and accuracy to determine
      whether OMZs are anoxic or contain 1-2 MUM O(2). With the introduction of the
      STOX (switchable trace oxygen) sensor, the level for accurate quantification has
      been lowered by a factor of 1000. By analysis with STOX sensors, O(2) can be
      prevented from reaching the sensing cathode by another cathode (front guard
      cathode), and it is the amplitude in signal by polarization/depolarization of
      this front guard that is used as a measure of the O(2) concentration. The STOX
      sensors can be used in situ, most conveniently connected to a conventional CTD
      (conductivity, temperature, and depth analyzer) along with a conventional oxygen
      sensor, and they can be used for monitoring O(2) dynamics during laboratory
      incubations of low-O(2) media such as OMZ water. The limiting factors for use of
      the STOX sensors are a relatively slow response, with measuring cycle of at least
      30 s with the current design, and fragility. With improved procedures for
      construction, the time for a complete measuring cycle is expected to come down to
      about 10 s.

PMID- 21185444
TI  - Protocol for the measurement of nitrous oxide fluxes from biological wastewater
      treatment plants.
AB  - The overarching goal herein was to develop a protocol that could be used to
      generate consistent information on the generation and emission of nitrous oxide
      (N(2)O) from open-surface wastewater treatment bioreactors. The developed
      protocol was reviewed and endorsed by the United States Environmental Protection
      Agency (USEPA), whereupon it was used to determine N(2)O emissions from a wide
      array of wastewater treatment processes across the United States. Scaled-down
      variants of the protocol have also since been adopted for lab-scale measurements.
      The protocol consists of a combination of elements that entail real-time online
      measurement of headspace N(2)O concentrations, supplemented by discrete
      measurements of liquid-phase N(2)O and other routinely monitored wastewater and
      process parameters. Notably, the advective flow rate of headspace gas is also
      directly measured.

PMID- 21185443
TI  - Regulation and measurement of nitrification in terrestrial systems.
AB  - Understanding nitrification rates and their regulation continues as a key area of
      research for assessing human's increasing impact on the terrestrial N cycle. We
      review the organisms and processes responsible for nitrification in terrestrial
      systems. The control of nitrification by substrate availability is discussed with
      particular attention to the factors affecting ammonia/ammonium availability. The
      effects on nitrification rates of environmental controls including oxygen, water
      potential, temperature and pH are described. With this general understanding of
      the factors affecting nitrification rates as a basis, we present an in depth
      analysis of methods used to measure nitrification in terrestrial systems. Net,
      gross and potential nitrification rate measurements are explained including the
      use of isotopes and inhibitors to measure rates in soils. Methods for the
      estimation of nitrification kinetics and modeling are briefly described. Future
      challenges will require understanding the factors controlling nitrification
      across spatial scales from ecosystems to soil microsites if we are to sustainably
      manage reactive nitrogen in terrestrial environments.

PMID- 21185445
TI  - Genetic transformation of ammonia-oxidizing bacteria.
AB  - The study of traits of ammonia-oxidizing bacteria (AOB) by genetic transformation
      is an approach that is facilitated by the availability of AOB genome sequences.
      To transform an AOB, a vector construct is introduced into the cells by
      electroporation or conjugation to effect the inactivation, complementation, or
      expression of a selected gene. For inactivation studies, the vector construct
      should contain the gene of interest with an antibiotic resistance cassette and
      recombine into the cell's chromosome. For gene expression studies, a wide-host
      range vector with a transcriptional gene fusion can be used to test for gene
      roles. For gene complementation studies, a wide-host range vector expressing the
      inactivated gene can be used to recover the lost function in an AOB mutant
      strain. This chapter is a compilation of the methods that have been used to
      transform the AOB Nitrosomonas europaea and Nitrosospira multiformis and of the
      considerations and caveats to successfully produce, maintain, and store AOB
      transformants. The protocols may be applied to other AOB.

PMID- 21185446
TI  - Dissecting iron uptake and homeostasis in Nitrosomonas europaea.
AB  - The chemolithoautotroph Nitrosomonas europaea oxidizes about 25 mol of NH(3) for
      each mole of CO(2) that is converted to biomass using an array of heme and
      nonheme Fe-containing proteins. Hence mechanisms of efficient iron (Fe) uptake
      and homeostasis are particularly important for this Betaproteobacterium. Among
      nitrifiers, N.europaea has been the most studied to date. Characteristics that
      make N.europaea a suitable model to study Fe uptake and homeostasis are as
      follows: (a) its sequenced genome, (b) its capability to grow relatively well in
      0.2 MUM Fe in the absence of heterologous siderophores, and (c) its amenability
      to mutagenesis. In this chapter, we describe the methodology we use in our
      laboratory to dissect Fe uptake and homeostasis in the ammonia oxidizer N.
      europaea.

PMID- 21185447
TI  - Production of recombinant multiheme cytochromes c in Wolinella succinogenes.
AB  - Respiratory nitrogen cycle processes like nitrification, nitrate reduction,
      denitrification, nitrite ammonification, or anammox involve a variety of
      dissimilatory enzymes and redox-active cofactors. In this context, an intriguing
      protein class are cytochromes c, that is, enzymes containing one or more
      covalently bound heme groups that are attached to heme c binding motifs (HBMs) of
      apo-cytochromes. The key enzyme of the corresponding maturation process is
      cytochrome c heme lyase (CCHL), an enzyme that catalyzes the formation of two
      thioether linkages between two vinyl side chains of a heme and two cysteine
      residues arranged in the HBM. In recent years, many multiheme cytochromes c
      involved in nitrogen cycle processes, such as hydroxylamine oxidoreductase and
      cytochrome c nitrite reductase, have attracted particular interest. Structurally,
      these enzymes exhibit conserved heme packing motifs despite displaying very
      different enzymic properties and largely unrelated primary structures. The
      functional and structural characterization of cytochromes c demands their
      purification in sufficient amounts as well as the feasibility to generate site
      directed enzyme variants. For many interesting organisms, however, such systems
      are not available, mainly hampered by genetic inaccessibility, slow growth rates,
      insufficient cell yields, and/or a low capacity of cytochrome c formation.
      Efficient heterologous cytochrome c overproduction systems have been established
      using the unrelated proteobacterial species Escherichia coli and Wolinella
      succinogenes. In contrast to E. coli, W. succinogenes uses the cytochrome c
      biogenesis system II and contains a unique set of three specific CCHL isoenzymes
      that belong to the unusual CcsBA-type. Here, W. succinogenes is presented as host
      for cytochrome c overproduction focusing on a recently established gene
      expression system designed for large-scale production of multiheme cytochromes c.

PMID- 21185448
TI  - Techniques for investigating hydroxylamine disproportionation by hydroxylamine
      oxidoreductases.
AB  - Hydroxylamine, an important intermediate in ammonia oxidation by ammonia
      oxidizing bacteria (AOB), is inherently unstable with respect to
      disproportionation. The process is slow in neutral solutions, but could
      potentially be catalyzed by enzymes such as the hydroxylamine oxidoreductases,
      which normally catalyze the oxidation of ammonia to nitrite in the AOB.
      Disproportionation could be physiologically important to some AOB under
      microaerobic conditions, and could also confound in vitro analyses if it occurs
      and is not taken into consideration. This chapter presents methods for detecting
      ammonia, nitric oxide, nitrite, nitrous oxide, and isotopically labeled
      dinitrogen, which are the most thermodynamically favored products of
      hydroxylamine disproportionation.

PMID- 21185449
TI  - Liquid chromatography-mass spectrometry-based proteomics of Nitrosomonas.
AB  - During the last century, the research on aerobic ammonium-oxidizing bacteria
      (AOB) lead to many exciting physiological and biochemical discoveries.
      Nevertheless the molecular biology of AOB is not well understood. The
      availability of the genome sequences of several Nitrosomonas species opened up
      new possiblities to use state of the art transcriptomic and proteomic tools to
      study AOB. With the currect technology, thousands of proteins can be analyzed in
      several hours of measurement and translated proteins can be detected at femtomole
      and attomole concentrations. Moreover, it is possible to use mass spectrometry
      based proteomics approach to analyze the expression, subcellular localization,
      posttranslational modifications, and interactions of translated proteins. In this
      chapter, we describe our LC-MS/MS methodology and quality control strategy to
      study the protein complement of Nitrosomonas eutropha C91.

PMID- 21185450
TI  - The geochemical record of the ancient nitrogen cycle, nitrogen isotopes, and
      metal cofactors.
AB  - The nitrogen (N) cycle is the only global biogeochemical cycle that is driven by
      biological functions involving the interaction of many microorganisms. The N
      cycle has evolved over geological time and its interaction with the oxygen cycle
      has had profound effects on the evolution and timing of Earth's atmosphere
      oxygenation (Falkowski and Godfrey, 2008). Almost every enzyme that
      microorganisms use to manipulate N contains redox-sensitive metals.
      Bioavailability of these metals has changed through time as a function of varying
      redox conditions, and likely influenced the biological underpinnings of the N
      cycle. It is possible to construct a record through geological time using N
      isotopes and metal concentrations in sediments to determine when the different
      stages of the N cycle evolved and the role metal availability played in the
      development of key enzymes. The same techniques are applicable to understanding
      the operation and changes in the N cycle through geological time. However, N and
      many of the redox-sensitive metals in some of their oxidation states are mobile
      and the isotopic composition or distribution can be altered by subsequent
      processes leading to erroneous conclusions. This chapter reviews the enzymology
      and metal cofactors of the N cycle and describes proper utilization of methods
      used to reconstruct evolution of the N cycle through time.

PMID- 21185451
TI  - Implementation of Gold deconvolution for enhanced energy resolution in EEL
      spectra.
AB  - Gold's iterative deconvolution algorithm has been applied to one-dimensional EEL
      spectra from hexagonal BN. The experimental resolution was varied from 1.1 to
      2.25 eV and Gold's algorithm was able to restore low-loss and core-loss spectra
      overall well. To estimate the instrument response function, the most convenient
      method was to extract the zero-loss peak from the low-loss spectrum. By instead
      using low-loss spectra as kernel, as suggested by Egerton, enhanced energy
      resolution could also be obtained with plural scattering simultaneously removed.
      It is further shown how the FWHM of the pi* peak in the boron K-edge of hexagonal
      BN is reduced from 1.4 to 0.7 eV with almost no noise amplification after 500
      iterations while resolving the sigma* doublet. The result was almost identical
      after a stunning 5000-10,000 iterations, implying that Gold's method converges
      and can be stable for a large number of iterations. However, for lower-intensity
      spectra the number of iterations is limited. The results close to the intense
      zero-loss peak were uncertain and further testing with better experimental
      resolution is recommended. It is also found that to improve the resolution and
      not just sharpen the spectra, a large number of iterations is required.

PMID- 21185453
TI  - A simple algorithm for measuring particle size distributions on an uneven
      background from TEM images.
AB  - Nanoparticles have a wide range of applications in science and technology. Their
      sizes are often measured using transmission electron microscopy (TEM) or X-ray
      diffraction. Here, we describe a simple computer algorithm for measuring particle
      size distributions from TEM images in the presence of an uneven background. The
      approach is based on adaptive thresholding, making use of local threshold values
      that change with spatial coordinate. The algorithm allows particles to be
      detected and characterized with greater accuracy than using more conventional
      methods, in which a global threshold is used. Its application to images of
      heterogeneous catalysts is presented.

PMID- 21185452
TI  - Images of paraffin monolayer crystals with perfect contrast: minimization of beam
      induced specimen motion.
AB  - Quantitative analysis of electron microscope images of organic and biological two
      dimensional crystals has previously shown that the absolute contrast reached only
      a fraction of that expected theoretically from the electron diffraction
      amplitudes. The accepted explanation for this is that irradiation of the specimen
      causes beam-induced charging or movement, which in turn causes blurring of the
      image due to image or specimen movement. In this paper, we used three different
      approaches to try to overcome this image-blurring problem in monolayer crystals
      of paraffin. Our first approach was to use an extreme form of spotscan imaging,
      in which a single image was assembled on film by the successive illumination of
      up to 50,000 spots, each of a diameter of around 7 nm. The second approach was to
      use the Medipix II detector with its zero-noise readout to assemble a time-sliced
      series of images of the same area in which each frame from a movie with up to 400
      frames had an exposure of only 500 electrons. In the third approach, we simply
      used a much thicker carbon support film to increase the physical strength and
      conductivity of the support. Surprisingly, the first two methods involving dose
      fractionation in space or time produced only partial improvements in contrast
      whereas the third approach produced many virtually perfect images, where the
      absolute contrast predicted from the electron diffraction amplitudes was observed
      in the images. We conclude that it is possible to obtain consistently almost
      perfect images of beam-sensitive specimens if they are attached to an
      appropriately strong and conductive support; however great care is needed in
      practice and the problem remains of how to best image ice-embedded biological
      structures in the absence of a strong, conductive support film.

PMID- 21185454
TI  - Effects of higher oscillation modes on TM-AFM measurements.
AB  - The finite element method and molecular dynamics simulations are used for
      modeling the AFM microcantilever dynamics and the tip-sample interaction forces,
      respectively. Molecular dynamics simulations are conducted to calculate the tip
      sample force data as a function of tip height at different lateral positions of
      the tip with respect to the sample. The results demonstrate that in the presence
      of nonlinear interaction forces, higher eigenmodes of the microcantilever are
      excited and play a significant role in the tip and sample elastic deformations.
      Using comparisons between the results of FEM and lumped models, how some aspects
      of the system behavior can be hidden when the point-mass model is used is
      illustrated.

PMID- 21185455
TI  - Preparation of thin ceramic monofilaments for TEM observation with novel
      embedding processes.
AB  - An applicable method to prepare transmission electron microscopy specimens from
      ceramic fibers for longitudinal and cross-sectional observations is investigated.
      The method includes novel embedding processes to fix fibers, a polishing process
      using a self-manufactured device to get uniformly low thickness (40 MUm for L
      fiber, 60 MUm for C-fiber), a one-side dimpling process to grind the specimen to
      near electron transparency (about 5 MUm in thickness for both L-fiber and C
      fiber) and an efficient ion milling process using calculated parameters. These
      techniques are reliable to accomplish the preparation with high quality in a
      relatively short time. Many factors related to the preparation processes are
      discussed.

PMID- 21185456
TI  - Quantitative EELS analysis of zirconium alloy metal/oxide interfaces.
AB  - Zirconium alloys have been long used for fuel cladding and other structural
      components in water-cooled nuclear reactors, but waterside corrosion is a primary
      limitation on both high fuel burn-up and extended fuel cycle operation.
      Understanding the processes that occur at the metal/oxide interface is crucial
      for a full mechanistic description of the oxidation process. In this paper we
      show that reliable quantification of the oxygen content at the metal/oxide
      interface can be obtained by Electron Energy Loss Spectrometry (EELS) if enough
      care is taken over both the preparation of Transmission Electron Microscopy (TEM)
      samples and the methodology for quantification of the EELS data. We have reviewed
      the accuracy of theoretically calculated inelastic partial scattering cross
      sections and effective inelastic mean-free-paths for oxygen and zirconium in
      oxidized Zr-alloy samples. After careful recalibration against a ZrO2 powder
      standard, systematic differences in the local oxygen profile across the interface
      in different zirconium alloys were found. The presence of a sub-stoichiometric
      oxide layer (a suboxide) was detected under conditions of slow oxide growth but
      not where growth was more rapid. This difference could arise from the different
      corrosion resistances of the alloys or, more likely, as a result of the
      transition in oxidation behaviour, which refers to a sharp increase in the
      oxidation rate when the oxide is a few microns thick.

PMID- 21185457
TI  - Quantification of the lateral detachment force for bacterial cells using atomic
      force microscope and centrifugation.
AB  - To determine the lateral detachment force for individual bacterial cells, a
      quantitative method using the contact mode of an atomic force microscope (AFM)
      was developed in this study. Three key factors for the proposed method, i.e. scan
      size, scan rate and cantilever choice, were evaluated and optimized. The scan
      size of 40*40 MUm2 was optimal for capturing sufficient number of adhered cells
      in a microscopic field and provide adequate information for cell identification
      and detachment force measurement. The scan rate affected the measurement results
      significantly, and was optimized at 40 MUm/s considering both force measurement
      accuracy and experimental efficiency. The hardness of applied cantilevers also
      influenced force determination. The proposed protocol for cantilever selection is
      to use those with the lowest spring constant first and then step up to a harder
      cantilever until all cells are detached. The lateral detachment force of
      Escherichia coli cells on polished stainless steel and a glass-slide coated with
      poly-l-lysine were measured as 0.763+/-0.167 and 0.639+/-0.136 nN, respectively.
      The results showed that the established method had good repeatability and
      sensitivity to various bacteria/substrata combinations. The detachment force
      quantified by AFM (0.639+/-0.136 nN) was comparable to that measured by the
      centrifugation method (1.12 nN).

PMID- 21185458
TI  - A method for accurate localisation of EBSD pattern centres.
AB  - The moving screen technique for pattern centre localisation is revisited. A cross
      correlation based iterative procedure is developed to find both the zoom factor
      and the zoom centre (which is also the pattern centre) between two EBSD
      diffraction patterns acquired at two camera positions. The procedure involves two
      steps: first, a rough estimate of the pattern centre position and zoom factor
      (the ratio of the two detector distances) is obtained by cross-correlating the
      entire images. Then, based on this first estimate, cross-correlation of smaller
      regions of interest (ROIs) gives the displacement field which is interpreted as a
      zoom factor misfit coupled with a zoom centre position misfit. These misfits are
      iteratively decreased until the displacement field is reduced to the noise level.
      The procedure is first applied to simulated patterns and it is shown that the
      iterative procedure converges very rapidly to the exact solution with an accuracy
      better than 1/100th of pixel. The potential of this technique for experimental
      patterns is discussed and recommendations for new EBSD detectors are proposed.

PMID- 21185459
TI  - Combining moire patterns and high resolution transmission electron microscopy for
      in-plane thin films thickness determination.
AB  - This paper reports the coupling of HRTEM and moire pattern observations, allowing
      the determination of the thickness ratio of two superimposed crystals. Pseudo
      lattice fringes are observed using identical TEM experimental conditions as for
      observing moire patterns. The pseudo-lattice spacing is first calculated in the
      dynamical theory framework in two beam conditions. This approach shows a linear
      behavior of the spacing as a function of the thickness ratio of the two crystals.
      The roles of sample crystallographic orientation and sample thickness on the
      thickness ratio determination are discussed from multi-beam simulations. Finally,
      the method is applied on a bimetallic CuAg core-shell nanoparticle of a known
      structure. It is demonstrated that for this particle, the thickness ratio of Cu
      and Ag can be determined with an error that results in a precision less than 0.75
      nm on the Cu and Ag thicknesses. The advantages of the technique are the use of
      an in-plane sample configuration and a single HRTEM image.

PMID- 21185460
TI  - Robust determination of Young's modulus of individual carbon nanotubes by quasi
      static interaction with Lorentz forces.
AB  - Young's modulus of an individual multi-wall carbon nanotube has been determined
      by the method of quasi-static transverse bending due to a Lorentz force observed
      in situ in a transmission electron microscope. The deflection of the nanotube
      allows the determination of Young's modulus using Euler-Bernoulli's beam
      equation. Because we determine the specific dependence of the deflection on the
      position along the nanotube axis, it is possible to gain insight into the type of
      mountings and furthermore allows for an estimation of the homogeneity of the
      nanotube. Both properties have been found to be of importance to determine
      Young's modulus. It was found to be higher by up to a factor of 1.6 compared to
      the value obtained by assuming rigid mountings.

PMID- 21185461
TI  - Object-wave reconstruction by carbon film-based Zernike- and Hilbert-phase plate
      microscopy: a theoretical study not restricted to weak-phase objects.
AB  - Transmission electron microscopy phase-contrast images taken by amorphous carbon
      film-based phase plates are affected by the scattering of electrons within the
      carbon film causing a modification of the image-wave function. Moreover, image
      artefacts are produced by non-centrosymmetric phase plate designs such as the
      Hilbert-phase plate. Various methods are presented to correct phase-contrast
      images with respect to the scattering of electrons and image artefacts induced by
      phase plates. The proposed techniques are not restricted to weak-phase objects
      and linear image formation. Phase-contrast images corrected by the presented
      methods correspond to those taken by an ideal centrosymmetric, matter-free phase
      plate and are suitable for object-wave reconstruction.

PMID- 21185462
TI  - Mapping titanium and tin oxide phases using EELS: an application of independent
      component analysis.
AB  - We study materials that present challenges for conventional elemental mapping
      techniques and can in some cases be treated successfully using independent
      component analysis (ICA). In this case the material in question is obtained from
      a TiO2-SiO2 solid solution that is spinodally decomposed into TiO2 rich-SnO2 rich
      multilayers. Conventional elemental mapping is difficult because the edges most
      easily mapped for these elements (Ti-L, Sn-M and O-K) all have onsets within the
      same 80 eV range. ICA is used to separate entire spectral signals corresponding
      to particular material phases or molecular units rather than particular elements
      and is thus able to distinguish between TiO2 and SnO2. We show that
      quantification of oxide species can be performed by different methods that
      require extra assumptions, but nevertheless should be feasible in many cases.

PMID- 21185463
TI  - [Informations for the infertile couple].
AB  - The aim of the first consultation related to infertility is supposed to be the
      optimization of all factors that can increase the chances of pregnancy: more
      frequent sexual intercourse during the fertility windows; lifestyle modifications
      (better diet, decreased exposure to tobacco or other toxics); older couples can
      enjoy the same advice but should be proposed a quicker medical support. Maternal
      preconceptional advice must be transmitted. A testicular cancer must always be
      excluded in infertile men, while the risk of hormone-dependent cancers in
      infertile women remains undetermined. With the results of this first
      consultation, couples will generally be proposed the best solution to achieve
      their parental project: ovarian stimulation assisted reproductive technology
      (IUI, IVF or ICSI) or adoption.

PMID- 21185464
TI  - [Guidelines for clinical practice risks associated with laparoscopic entry:
      methods].

PMID- 21185465
TI  - [Risks associated with laparoscopic entry].
AB  - OBJECTIVE: To provide guidelines for clinical practice from the French college of
      obstetrics and gynecology (CNGOF), based on the best evidence available, on
      laparoscopic entry techniques and technologies and their associated
      complications. MATERIALS AND METHODS: French and English-language articles from
      Medline, PubMed, and the Cochrane Database were searched, using the key words:
      laparoscopic entry, laparoscopy access, pneumoperitoneum, Veress needle, open
      (Hasson), direct trocar, visual entry, shielded trocars, optical trocar radially
      expanded trocars, and laparoscopic complications. RESULTS: Except for high-risk
      subgroups, laparoscopic entry should be performed using one of the four
      followings techniques (grade B): trans-umbilical trocar insertion after creation
      of a pneumoperitoneum using Veress needle; open-laparoscopy (Hasson technique),
      left upper quadrant (LUQ) laparoscopic entry or trans-ombilical direct trocart
      insertion. Because of insufficient evaluation, radially expanding trocars and
      visual entry systems (optical trocars) should not be used as a first-line
      technique (grade C). Left upper quadrant (LUQ, Palmer's) laparoscopic entry
      technique should be used in patients with previous midline incision laparotomy
      (grade B). In pregnant women, the level of insertion of the first trocar should
      be adapted to uterine volume (grade B). In second trimester, an open (Hasson) or
      a LUQ technique should be performed (grade C). In third trimester, an open
      (Hasson) technique (above the level of uterine fundus) should be performed when a
      laparoscopy is indicated. For pneumoperitoneum establishment using Veress needle
      insertion, one or several Veress needle safety tests or checks should be done
      (grade B) and waggling of the Veress needle from side to side must be avoided, as
      this can enlarge a bowel or vascular injury. In the Veress needle method of
      entry, the abdominal pressure should be increased immediately prior to insertion
      of the first trocar (from 15 to 25 mmHg) (grade C). CONCLUSION: Implementation of
      this guideline should optimize the decision-making process in choosing a
      particular technique to enter the abdomen during laparoscopy.

PMID- 21185466
TI  - [Gestational diabetes. Introduction].

PMID- 21185467
TI  - [Method and organization].

PMID- 21185468
TI  - [Definitions, epidemiology, risk factors].
AB  - Gestational diabetes mellitus is defined as carbohydrate intolerance that begins
      or is first recognized during pregnancy. Its prevalence, generally situated
      between 2-6%, may reach 10-20% in high-risk populations, with an increasing trend
      across most racial/ethnic groups studied. Among classical risk factors, previous
      gestational diabetes, older maternal age and obesity have the most important
      impact on gestational diabetes risk. Racial/ethnic origin and family history of
      type 2 diabetes have a significant but moderate impact (except for type 2
      diabetes in siblings). Several non classical factors have been recently
      characterized, either physiological (low birth weight and short maternal height)
      or pathological (polycystic ovaries). The multiplicity of risk factors and their
      interactions results in a low reliability of risk prediction on an individual
      basis.

PMID- 21185469
TI  - [Maternal outcome of gestational diabetes mellitus].
AB  - OBJECTIVE: To estimate maternal outcome of treated or untreated gestational
      diabetes mellitus (GDM). METHODS: French and English publications were searched
      using PubMed and Cochrane library. RESULTS: The diagnosis of GDM gathers a high
      risk population of preeclampsia and cesarean section (EL3). These risks are
      positively correlated with the level of hyperglycemia in a linear way (EL2).
      Intensive treatment of mild GDM compared with routine care reduces the risk of
      pregnancy-induced hypertension (preeclampsia, gestational hypertension).
      Moreover, it does not increase the risk of operative vaginal delivery, cesarean
      section and postpartum haemorrhage (EL1). Overweight, obesity and maternal
      hyperglycemia are independent risk factors for preeclampsia (EL2). Their
      association with GDM increases the risk of preeclampsia and cesarean section
      compared to diabetic women with normal body mass index (EL3). The association of
      several risk factors (such as advanced maternal age, pre-existing chronic
      hypertension, pre-existing nephropathy, obesity, suboptimal glycemic control)
      increases the risk of preeclampsia. In that case, the classical follow-up (blood
      pressure measurement, proteinuria) should be more frequent than monthly
      (professional consensus). The risk of cesarean section is increased by
      macrosomia, whether it was prenatally suspected or not. But this increased risk
      remains whatever the birth weight is (EL3). Diagnosis and treatment of GDM do not
      reduce the risk of severe perineal lesions, operative vaginal delivery and
      postpartum haemorrhage (EL2). Some psychological symptoms, such as anxiety and
      alteration of self-perception, can occur at the diagnosis of GDM (EL3). The
      treatment of GDM seems to reduce the risk of postpartum depression symptoms
      (EL2). CONCLUSION: Most of the informations published on GDM cover the risks of
      preeclampsia and cesarean section. Intensive care of GDM reduces theses risks.
      The pregnancy follow-up should be adjusted to the risk factors.

PMID- 21185470
TI  - [Fetal and neonatal complications of gestational diabetes: perinatal mortality,
      congenital malformations, macrosomia, shoulder dystocia, birth injuries, neonatal
      outcomes].
AB  - OBJECTIVE: To evaluate perinatal outcomes in case of gestational diabetes (GD)
      treated or not. METHODS: This study is based on Pubmed search and on NICE and HAS
      recommendations. RESULTS: Moderate or severe GD increases the risk of foetal and
      neonatal complications [EL1]. The risk of malformation is slightly increased in
      case of GD compared with non diabetic population [EL2]. The increased risk of
      malformation is probably linked to undiagnosed cases of type 2 diabetes among
      cases of GD [EL2]. There is a continuous association of maternal glucose levels
      with increased birth weight [EL2]. The incidence of macrosomia decreases when
      diabetes is treated [EL1]. Data from the literature don't allow estimating
      precise risk of hypertrophic cardiomyopathy in case of GD, but severe clinical
      form is exceptional. Risk of neonatal asphyxia and perinatal death is not
      increased in case of GD [EL2]. Birth injuries and nerve palsy are rare in case of
      GD, and there is no evidence for increased incidence of such events when GD is
      not treated. The risk of neonatal respiratory distress whatever is the cause, is
      difficult to estimate. There is no evidence to establish a link between GD and
      neonatal respiratory distress. It is difficult to estimate the risk of neonatal
      hypoglycaemia because of various definitions used in the different studies, but
      the frequency of hypoglycaemia treated with IV glucose is low [EL1]. The risk of
      hypocalcemia [EL4] and hyperbilirubinemia [EL1] is similar to that of the general
      population. CONCLUSION: Severe perinatal complications specifically linked to GD
      are rare. Macrosomia is the principal neonatal adverse outcomes demonstrated in
      case of GD. It is the main factor related to the complications reported in case
      of GD. Maternal obesity is an additional risk factor of neonatal adverse outcomes
      and is independent from the diabetes.

PMID- 21185471
TI  - [Relevance of gestational diabetes mellitus screening and comparison of selective
      with universal strategies].
AB  - OBJECTIVES: To assess the relevance of gestational diabetes mellitus (GDM)
      screening policy and to compare selective with universal screening. METHODS:
      Systematic review of all French and English languages publications in Medline and
      Cochrane Databases, published since 1990. RESULTS: Maternal hyperglycemia is
      associated with increased maternal and neonatal complications. The 75 g OGTT
      (Oral Glucose Tolerance Test) is a valid and reliable test for GDM diagnosis.
      Treatment of GDM reduces perinatal complications. Selective screening allows to
      limit false positive rate and to concentrate medical resources. Nevertheless,
      screening might be more difficult to perform and lead to miss up to 45% of GDM
      cases. Universal screening offers higher sensitivity but leads to more
      therapeutic interventions whose benefit and cost/efficiency ratio need to be
      estimated in low risk women. CONCLUSION: The benefits of GDM screening and
      treatment have only been proven for women with GDM risk factors. Their relevance
      in women without risk factor remains controversial.

PMID- 21185472
TI  - [When should we screen for gestational diabetes?].
AB  - AIM: Consider the arguments for screening outside the classical period of 24-28
      SA. MATERIALS AND METHODS: A literature search between 1990 and 2010 was
      performed using the Pubmed and Cochrane database. Foreign societies guidelines
      were also consulted. RESULTS: Screening for gestational diabetes is recommended
      between 24 and 28 weeks of pregnancy, when glucose tolerance deteriorates.
      However, for patients with certain risk factors, the increasing prevalence of
      type 2 diabetes in women of childbearing age requires earlier screening. Fasting
      blood glucose should be measured at the first visit during pregnancy for these
      patients. The diagnostics threshold is the same as for patients who are not
      pregnant, i.e. blood glucose > 1.26 g/L. On the other hand, the interest of
      screening for gestational diabetes at the beginning of pregnancy in the case of
      certain risk factors is not supported by prospective studies. It is therefore not
      recommended to perform an OGTT in early pregnancy in order to diagnose
      gestational diabetes. The search for a gestational diabetes, regardless of
      screening policy recommended, has to be performed between 24 and 28 weeks
      gestational age. There are no reasons to consider a new search for gestational
      diabetes at later stages.

PMID- 21185473
TI  - [Methods of screening of gestational diabetes between 24 and 28 weeks'
      gestation].
AB  - The aim of this review is to answer the question "how to detect the gestational
      diabetes mellitus (GDM) between 24 and 28 weeks of gestation?". Two approaches
      are well established: one-step approach (75 g-OGTT) and two-steps approach (50 g
      followed 100g-OGTT). The analysis of the literature shows that each of these
      methods has a good reproducibility close to 80 %, without requiring preliminary
      dietetics. The HAPO study provides consistent data about the 75 g-OGTT materno
      fetal morbidity related. Furthermore, the one-step approach, relationship two
      steps approach, has several advantages: reduction of time of diagnosis and
      primary care, better tolerance, simpler memorization. We recommend for the
      screening and the diagnosis of GDM an 75 g-OGTT with three measures: FPG, 1-h and
      2-h. The various alternative methods are discussed. The measure of the fasting
      blood glucose isolated between 24 and 28 weeks of gestation is not a relevant
      approach. None of the other alternative methods (HbA1c, fructosamine, glycosuria,
      random and postprandial plasma glucose) cannot be recommended. Indeed, these
      methods have been addressed in little numerous studies, among heterogeneous
      populations, using variable criteria, and variable sensitivity values. Only the
      HbA1c might be useful to detect a pre-pregnancy diabetes mellitus.

PMID- 21185474
TI  - [Diagnostic criteria for gestational diabetes mellitus].
AB  - AIM: To answer two questions: is there a threshold for pathological hyperglycemia
      after 24 weeks of gestation? What are the diagnostic criteria for gestational
      diabetes mellitus? MATERIAL AND METHODS: Review of the literature considering the
      relationships between glucose values and complications during pregnancy in women
      without specific care for this condition. Only the Hyperglycemia and Adverse
      Pregnancy Outcome (HAPO) study meets sufficient quality criteria. RESULTS:
      Increasing glucose values during pregnancy, either at fasting and after a 75-g
      oral glucose-tolerance test, are independently associated with adverse pregnancy
      outcomes, especially birth weight above the 90th percentile for gestational age,
      caesarian delivery and fetal hyperinsulinemia. There is no obvious threshold at
      which risks increase. The International Association of Diabetes Pregnancy Study
      Group has proposed, considering the glycemic values associated with a 1.75-fold
      increased risk of macrosomia, fetal hyperinsulinism and adiposity in the HAPO
      study, the following criteria: fasting plasma glucose >= 0.92 g/L (5.1 mmol/L)
      and/or 1-hour plasma glucose value >= 1.80 g/L (10.0 mmol/L) and/or 2-hour plasma
      glucose value >= 1.53 g/L (8.5 mmol/L). CONCLUSION: Choosing glycemic threshold
      to define gestational diabetes mellitus is necessarily arbitrary because of a
      continuum. Only experts may propose definition criteria.

PMID- 21185475
TI  - [Management of gestational diabetes].
AB  - BACKGROUND: Maternal and perinatal complications linked to gestational diabetes
      could be decreased with an intensive treatment. AIM: To assess the effect of
      various treatments, glycaemia targets and procedures for blood glucose self
      monitoring, on fetal and maternal prognosis. METHODS: Systematic review of
      literature studying the efficacy of the treatment of gestational diabetes to
      decrease fetal morbi-mortality thereof. Analysis based on bibliographic search in
      pubmed using the following keywords: "therapeutic", "treatment" and "gestational
      diabetes". RESULTS: Specific treatment of gestational diabetes (dietetics,
      physical exercise, blood glucose self-monitoring, insulin-therapy if appropriate)
      reduces severe perinatal complications (composite criterion), fetal macrosomia
      and pre-eclampsia compared to the absence of therapy, with however an increase in
      the number of triggered deliveries, and without any increase in the number of
      cesarean sections. Regarding oral antidiabetics, despite no difference was found
      in fetal or maternal prognosis upon treatment with glyburide, metformin, or
      insulin, they should not be prescribed. CONCLUSION: The treatment of "severe or
      moderate" gestational diabetes is recommended. Additional studies, in particular
      long-term studies in children, are warranted before oral antidiabetics can be
      used.

PMID- 21185476
TI  - [Obstetrical care in gestational diabetes and management of preterm labor].
AB  - OBJECTIVES: Search for data necessary to elaborate recommendations for
      obstetrical care in gestational diabetes and management of preterm labor.
      METHODS: Systematic review of the literature and levels of evidence. RESULTS: In
      case of gestational diabetes and in the absence of disease or other risk factor
      associated, there is no evidence to support a systematic rate of clinical follow
      up different from other pregnancy. The relevance of ultrasound estimates of fetal
      weight is limited. No formula is superior to others or to the simple measurement
      of abdominal circumference for the prediction of macrosomia (EL3). The usefulness
      of the research septal hypertrophy is not demonstrated (EL4). The systematic
      application of umbilical Doppler has no proven benefits in the absence of growth
      restriction or hypertension associated (EL4). Monthly ultrasound monitoring of
      the fetus can be proposed for diabetics on insulin or poorly controlled. In cases
      of gestational diabetes controlled by diet, cardiotocography of fetal heart rate
      has not proven useful. In poorly controlled diabetes and/or on insulin, the
      registration may be discussed taking into account other risk factors associated
      (EL4). A weekly recording of fetal heart rate is often recommended in case of
      type 2 diabetes discovered during pregnancy. In case of preterm labor, calcium
      channel blockers and oxytocin antagonists can be used without specific
      precautions. The risk of using beta-adrenergic outweighs the benefit.
      Administration of corticosteroid can be done under glycemic control, with insulin
      therapy if necessary. Screening test for gestational diabetes should not be
      performed within few days after last steroid injection.

PMID- 21185477
TI  - [Evaluation of the ovarian reserve].
AB  - AIMS: This literature review attempts to answer the following questions: 1) When
      making an assessment of ovarian reserve (OR) in an infertile woman? and 2) what
      is the investigation that best identifies situations of low OR in order to guide
      patients towards appropriate care? RESULTS: Some elements of the clinical
      examination should prompt us to rapidly perform OR tests: patients over 35 years,
      with cycle disorders or a history of pelvic disease, chemotherapy or
      radiotherapy. The most widely used OR tests are FSH, estradiol, inhibin B, antral
      follicle count (AFC), ovarian volume, Antimullerian hormone (AMH) and dynamic
      tests. Most studies evaluating these markers were performed within the frame of
      in vitro fertilization (IVF), and we have little information on their ability to
      predict spontaneous pregnancy. FSH seems an interesting marker to identify
      extreme situations of ovarian insufficiency when using a high threshold value.
      Estradiol assay must always be associated with it. The AFC and AMH both have a
      good ability to predict the response to ovarian stimulation in IVF. However,
      their association does not increase their strength of prediction. The ovarian
      volume, inhibin B as well as dynamic tests are not relevant markers. None of
      these markers can predict the chances of pregnancy in IVF. CONCLUSION: OR tests
      must be performed before assisted reproduction techniques (ART) and should
      include FSH, estradiol, and AMH or CFA. Each center must define its specific
      standards for the interpretation of results. This assessment will advise the
      couple about their chances of success in ART and the clinician to adapt its
      management.

PMID- 21185478
TI  - [Delivery (timing, mode, glycemic control) in women with gestational diabetes].
AB  - OBJECTIVES: To provide management guidelines for labor and delivery in women with
      gestational diabetes. MATERIALS AND METHODS: A literature search was performed
      using the Pubmed and Cochrane database. Foreign societies guidelines were also
      consulted. RESULTS: There is no additional information from recent studies that
      may suggest changing current French guidelines about timing of delivery in
      gestational diabetes. The incidence of shoulder dystocia is increased in women
      with gestational diabetes, especially when infants are weighing more than 4500 g.
      Elective cesarean section when the fetal weight was greater than or equal to 4250
      to 4500 g may reduce the risk of shoulder dystocia. Meticulous attention to
      avoiding maternal hyperglycemia during labor can prevent neonatal hypoglycemia.
      There is no significant role for x-ray pelvimetry in the management of
      gestational diabetes. CONCLUSION: Management of labor and delivery in women with
      gestational diabetes will mainly depend on estimated fetal weight, especially
      when macrosomia is present.

PMID- 21185479
TI  - [Management of neonates born to mothers with gestational diabetes: paediatric
      environment].
AB  - OBJECTIVE: To estimate the modalities of neonatal care for newborn from mother
      with gestational diabetes (GD) treated or not. METHODS: This study is based on
      Pubmed search and on NICE and HAS recommendations. RESULTS: There is no
      paediatric indication to organize the birth in a specialized structure, excepted
      in case of severe abnormality of the foetal growth, of severe malformation or of
      risk of prematurity. It is recommended to watch systematically the glycaemia of
      the newborn children of mother with GD treated by insulin or in case of
      macrosomia or growth restriction. The systematic surveillance of the glycaemia is
      not indicated at the child's of mother with GD treated by only diet and without
      abnormality of growth. The newborn should benefit from the usual surveillance of
      the neonatal icterus. The dosage of the calcemia and the realization of blood
      cells count are indicated according to the clinical signs. The realization of
      additional examinations in search of a cardiac, osseous or cerebral malformation
      must be directed according to the signs in the clinical examination. The
      indications of transfer of the newborn of mother with DG in neonatal unit are the
      same that for every newborn child. CONCLUSIONS: The newborn can be welcomed in
      the maternity of nearness except in case of prematurity, of severe malformations
      or of severe abnormality of the foetal growth. The care of the newborn of mother
      with DG, in particular for the prevention, the detection and the treatment of
      hypoglycaemias, will be improved by the existence of a protocol.

PMID- 21185480
TI  - [Postpartum and contraception after gestational diabetes].
AB  - Women who had gestational diabetes must have their glycemia closely checked after
      delivery to insure complete normalization. Few studies are published but breast
      feeding does not seem to modify the metabolic profile of the mother or the
      children. Contraception must take account associated risk factors. Very few
      studies are published and none notified a significant modification of the
      carbohydrate metabolism with hormonal contraception, either estroprogestative or
      progestative only. But associated obesity, hypertension or dyslipidemia need the
      prescription of a contraception with no vascular secondary effect. In these cases
      an intrauterine device represents a very good choice.

PMID- 21185481
TI  - [Outcomes in women with history of gestational diabetes mellitus. Screening and
      prevention of type 2 diabetes mellitus. Literature review].
AB  - Women with a history of gestational diabetes mellitus (GDM) are characterized by
      a high risk of type 2 diabetes mellitus (T2DM) (X 7), metabolic syndrome (X 2 to
      5) and cardiovascular diseases (X 1,7). Women with lesser degrees of glucose
      intolerance share the same risks. T2DM may occur from postpartum (5 to 14%) to
      several years later, up to 25 years. Some factors associated with T2DM are
      identified: obesity, early diagnostic before 24 weeks, high pregnancy OGTT blood
      glucose or insulinotherapy. Screening for T2DM only with fasting glucose provides
      less sensibility than with OGTT; HbA1c may supplant these dosages. The recurrence
      rate of GDM is between 30 and 84%, non-white ethnicity and insulinotherapy during
      GDM being the best proven predictors. High risk women need repeated life-long
      screenings for glycemic abnomalies, or when another pregnancy is planned. Among
      overweight or obese women with history of GDM who show minor glycoregulation
      disturbances, it is proved that modifications of lifestyle in intensive programs
      or metformin halve the risk of DT2. However, studies analysing practices show low
      adhesion to screening; without an intensive program, few women implement
      lifestyle modifications. These intensive programs should be implemented and
      proposed to high-risk women. Their therapeutic education should also include
      prevention of cardiovascular risk factors.

PMID- 21185482
TI  - [Management of the infertile couple. Introduction].

PMID- 21185483
TI  - [Long term outcome in children of mothers with gestational diabetes].
AB  - OBJECTIVES: To appreciate, in epidemiological studies, the impact of fetal
      exposure to gestational diabetes on the long term outcome of the offspring (type
      2 diabetes, overweight and obesity, metabolic syndrome and neurological
      complications). METHODS: A systematic search was conducted in Medline between
      January 1990 and April 2010. Prospective studies (follow-up of the offspring born
      of mothers with gestational diabetes) and retrospective studies (questionnaire
      about the parents'history of diabetes in diabetic patients) were searched and
      analysed. RESULTS: The fetal exposure to maternal gestational diabetes is a
      moderate risk factor for metabolic syndrome in the offspring. But some other
      perinatal risk factors of metabolic syndrome carry a bigger influence. The
      influence of genetic factors and maternal overweight may not be easily
      distinguished from the impact of fetal exposure to gestational diabetes.
      CONCLUSION: It remains uncertain if the control of maternal glycemia alone may be
      effective and sufficient to prevent the metabolic syndrome in the adult-aged
      offspring.

PMID- 21185484
TI  - [Anatomic evaluation of the female of the infertile couple].
AB  - One third of infertility cases are due to anatomical abnormalities of the female
      reproductive tract: endometrial polyps (33%), bilateral tubal blockage (12%),
      hydrosalpinx (7%), sub-mucosal fibroids (3%) and pelvic endometriosis. These may
      need surgical correction which could restore fertility. This review aim to
      determine which examinations should be performed first. Hysterosalpingography
      shows sensitivity of only 65% but it increases the achievement of spontaneous
      pregnancy by three times. Office hysteroscopy has an excellent sensitivity (>95%)
      for diagnosing intra-uterine lesions. Pelvic ultrasound, whose good sensitivity
      is improved by adding 3D imaging and hysterosonography, seems as efficient as
      office hysteroscopy in diagnosing uterine cavity abnormalities. Moreover, it also
      efficiently diagnoses pelvic diseases such as hydrosalpinx or endometrioma
      without laparoscopy. A first line laparoscopy is indicated in for woman suspected
      of endometriosis or tubal pathology (history of complicated appendicitis,
      previous pelvic surgery, pelvic inflammatory disease). For the others straight
      forward cases, the majority of patients, hysterosalpingography and pelvic
      ultrasound seem to be sufficient as primary diagnostic tool.

PMID- 21185486
TI  - [Methods and organization].

PMID- 21185485
TI  - [Evaluation of the male of the infertile couple].
AB  - The exploration of male infertility combines clinical examination and
      complementary analysis, including biology and ultrasonography. The purpose of
      this review is to analyze the data available on the accuracy of interview,
      testicular ultrasonography, sperm analysis and post-coital test. Medical history
      and patient's interview remain central in the exploration of the infertile man.
      Despite some limitations, studies on testicular sonography confirm the high
      prevalence of testicular lesions in infertile men. Up to now, sperm analysis
      remains the pivotal element of the exploration of male fertility. The new WHO
      manual for semen analysis published in 2010 should help in redefining its place
      in the global exploration of male infertility. Despite its statutory character in
      France, the interest of systematic sperm bacterial examination remains to be
      demonstrated. Concerning sperm DNA fragmentation, its use as a first-line test
      should not be recommended. Finally, high levels of evidence do not exist
      concerning the use of post-coital test as a predictor of pregnancy in infertile
      couples.

PMID- 21185487
TI  - [Preservation of fertility in case of sterilizing treatment].
AB  - The different options of fertility preservation must be approached with all
      patients before initiating any cancer therapy and physicians should refer each
      patient treated during their reproductive years to specialists in a specialized
      center that will evaluate the best available alternatives to preserve male and
      female fertility.The only efficiently proven ways of fertility preservation are
      sperm cryopreservation for men and embryo cryopreservation to preserve couple
      fertility. However, the recent progress observed with oocyte cryopreservation (in
      particular the oocyte vitrification) may change our practices in the future if
      vitrification is allowed in France. Although the law of Bioethics of 2004
      authorizes the ovarian cryopreservation today, its modalities of use stay at
      present at the stage of the research. But in spite of the low number of published
      births today in France and in the world, the ovarian tissue cryopreservation is a
      promising technique. It remains the last possible alternative to protect
      fertility of prepubertal girls. The sperm cryopreservation must be systematically
      proposed to all men (even teenagers) undergoing a treatment for cancer
      potentially harmful for their fertility whatever their sperm quality. The
      testicular tissue cryopreservation is also a method to be discussed for adults,
      teenagers in case of failure of sperm banking or for prepubertal boys.

PMID- 21185488
TI  - [Induction of ovulation].
AB  - OBJECTIVES: To elaborate guidelines for the use of different treatment and
      different protocols for ovarian stimulation. SEARCHED STRATEGY: We searched for
      all publications which described randomised controlled trial evaluating different
      ovarian stimulation protocols and different indications on PubMed, Medline and
      Cochrane Database. The keywords were: ovulation induction, citrate of clomiphene,
      gonadotropin, metformin, anti estrogens, anti aromatase, pulsatile GnRH
      administration, cancer, ovarian hyperstimulation, thrombosis, multiple
      pregnancies, and complications. Randomised controlled trials were first
      considered. Then was considered recent meta analysis and cohort study. We
      mentioned when literature was weak.

PMID- 21185489
TI  - [Reproductive surgery].
AB  - The place of surgery in the management of an infertile couple is still under
      debate. Good pregnancy outcomes in assisted reproductive technologies have led to
      a decrease in surgical indications. In this evidence based review, we updated our
      data of high powered articles in order to establish national guidelines for
      clinical practice about the role and benefits of surgery in principal etiologies
      of female infertility.

PMID- 21185490
TI  - [Assisted reproductive technologies place].
AB  - There are three kinds of infertility treatment: medical treatment, surgical
      treatment and assisted reproductive technology (ART). ART includes intra uterine
      insemination (IUI), in vitro fertilization (IVF) and intracytoplasmic sperm
      injection (ICSI). ART technologies made a lot of progress last years and their
      field of applications extended. Through literature reviews, IUI is recommended
      for unexplained infertility and discussed for male or cervical infertility. IVF
      is recommended for tubal and unexplained infertility. Limits between IVF and ICSI
      in case of male infertility remains unclear. In non mal infertility ICSI is not
      recommended.

PMID- 21185491
TI  - [Prognosis criteria for the management of the infertile couple].
AB  - Advanced maternal age, obesity and cigarette smoking are associated with
      decreased fertility, adverse Assisted Reproductive Technologies (ART) outcomes
      and fetal and neonatal complications. IVF failures increase dramatically in women
      aged between 42-43 years. Advanced paternal age is associated with fetal and
      neonatal adverse outcomes. However, it remains uncertain that advanced paternal
      age could impair IVF results. Obesity (Body mass index more than 30 kg/m(2)) is
      associated with lower fecundity, pregnancy complications and adverse ART results.
      The rate of complications is increasing with higher BMI. Cigarette smoking is
      associated with longer time to conceive and decreased IVF results. In case of
      infertility associated with obesity or cigarette smoking, physicians have to
      inform their patient about the benefits of smoking cessation and weight loss.
      However, maternal age had to be considered as the main prognosis factor before
      delaying ART because of dietary or smoking cessation program.

PMID- 21185493
TI  - Reply comments to 'Efficacy of a diazepam at preventing febrile seizure
      recurrence after febrile illness'.

PMID- 21185494
TI  - Images in cardiology. Aberrant origin of circumflex coronary artery from left
      subclavian artery.

PMID- 21185495
TI  - The aging heart and post-infarction left ventricular remodeling.
AB  - Aging is a risk factor for heart failure, which is a leading cause of death world
      wide. Elderly patients are more likely than young patients to experience a
      myocardial infarction (MI) and are more likely to develop heart failure following
      MI. The poor clinical outcome of aging in cardiovascular disease is recapitulated
      on the cellular level. Increase in stress exposure and shifts in signaling
      pathways with age change the biology of cardiomyocytes. The progressive
      accumulation of metabolic waste and damaged organelles in cardiomyocytes blocks
      the intracellular recycling process of autophagy and increases the cell's
      propensity toward apoptosis. Additionally, the decreased cardiomyocyte renewal
      capacity in the elderly, due to reduction in cellular division and impaired stem
      cell function, leads to further cardiac dysfunction and maladaptive responses to
      disease or stress. We review the cellular and molecular aspects of post
      infarction remodeling in the aged heart, and relate them to the clinical problem
      of post-infarction remodeling in elderly patients.

PMID- 21185496
TI  - Cerebral embolism following transcatheter aortic valve implantation: comparison
      of transfemoral and transapical approaches.
AB  - OBJECTIVES: The objective of this study was to compare the incidence of cerebral
      embolism (CE) as evaluated by diffusion-weighted magnetic resonance imaging (DW
      MRI) following transapical (TA) transcatheter aortic valve implantation (TAVI)
      versus transfemoral (TF) TAVI. BACKGROUND: The TA-TAVI approach avoids both the
      manipulation of large catheters in the aortic arch/ascending aorta and the
      retrograde crossing of the aortic valve, and this avoidance might lead to a lower
      rate of CE. METHODS: This was a prospective multicenter study including 60
      patients who underwent cerebral DW-MRI the day before and within the 6 days
      following TAVI (TF approach: 29 patients; TA approach: 31 patients). Neurologic
      and cognitive function assessments were performed at DW-MRI time points. RESULTS:
      The TAVI procedure was performed with the Edwards valve and was successful in all
      cases but one (98%). A total of 41 patients (68%) had 251 new cerebral ischemic
      lesions at the DW-MRI performed 4 +/- 1 days after the procedure, 19 patients in
      the TF group (66%) and 22 patients in the TA group (71%; p = 0.78). Most patients
      (76%) with new ischemic lesions had multiple lesions (median number of lesions
      per patient: 3, range 1 to 31). There were no differences in lesion number and
      size between the TF and TA groups. No baseline or procedural factors were found
      to be predictors of new ischemic lesions. The occurrence of CE was not associated
      with a measurable impairment in cognitive function, but 2 patients (3.3%) had a
      clinically apparent stroke within the 24 h following the procedure (1 patient in
      each group). CONCLUSIONS: TAVI is associated with a high rate of silent cerebral
      ischemic lesions as evaluated by DW-MRI, with no differences between the TF and
      TA approaches. These results provide important novel insight into the mechanisms
      of CE associated with TAVI and support the need for further research to both
      reduce the incidence of CE during these procedures and better determine their
      clinical relevance.

PMID- 21185497
TI  - Multiple biomarkers at admission significantly improve the prediction of
      mortality in patients undergoing primary percutaneous coronary intervention for
      acute ST-segment elevation myocardial infarction.
AB  - OBJECTIVES: We investigated whether multiple biomarkers improve prognostication
      in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary
      percutaneous coronary intervention. BACKGROUND: Few data exist on the prognostic
      value of combined biomarkers. METHODS: We used data from 1,034 STEMI patients
      undergoing primary percutaneous coronary intervention in a high-volume
      percutaneous coronary intervention center in the Netherlands and investigated
      whether combining N-terminal pro-brain natriuretic peptide, glucose, C-reactive
      protein, estimated glomerular filtration rate, and cardiac troponin T improved
      the prediction of mortality. A risk score was developed based on the strongest
      predicting biomarkers in multivariate Cox regression. The additional prognostic
      value of the strongest predicting biomarkers to the established prognostic
      factors (age, body weight, diabetes, hypertension, systolic blood pressure, heart
      rate, anterior myocardial infarction, and time to treatment) was assessed in
      multivariable Cox regression. RESULTS: During follow-up (median, 901 days), 120
      of the 1,034 patients died. In Cox regression, glucose, estimated glomerular
      filtration rate, and N-terminal pro-brain natriuretic peptide were the strongest
      predictors for mortality (p < 0.05, for all). A risk score incorporating these
      biomarkers identified a high-risk STEMI subgroup with a significantly higher
      mortality when compared with an intermediate- or low-risk subgroup (p < 0.001).
      Addition of the 3 biomarkers to established prognostic factors significantly
      improved prediction for mortality, as shown by the net reclassification
      improvement (0.481, p < 0.001) [corrected] and integrated discrimination
      improvement (0.0226, p = 0.03) [corrected]. CONCLUSIONS: Our data suggest that
      addition of a multimarker to a model including established risk factors improves
      the prediction of mortality in STEMI patients undergoing primary percutaneous
      coronary intervention. Furthermore, the use of a simple risk score based on these
      biomarkers identifies a high-risk subgroup.

PMID- 21185498
TI  - Prognostic biomarkers in ST-segment elevation myocardial infarction: a step
      toward personalized medicine or a tool in search of an application?

PMID- 21185499
TI  - Screening for copy number variation in genes associated with the long QT
      syndrome: clinical relevance.
AB  - OBJECTIVES: The aim of this study was to investigate, in a set of 93 mutation
      negative long QT syndrome (LQTS) probands, the frequency of copy number variants
      (CNVs) in LQTS genes. BACKGROUND: LQTS is an inherited cardiac arrhythmia
      characterized by a prolonged heart rate-corrected QT (QTc) interval associated
      with sudden cardiac death. Recent studies suggested the involvement of
      duplications or deletions in the occurrence of LQTS. However, their frequency
      remains unknown in LQTS patients. METHODS: Point mutations in KCNQ1, KCNH2, and
      SCN5A genes were excluded by denaturing high-performance liquid chromatography or
      direct sequencing. We applied Multiplex Ligation-dependent Probe Amplification
      (MLPA) to detect CNVs in exons of these 3 genes. Abnormal exon copy numbers were
      confirmed by quantitative multiplex PCR of short fluorescent fragment (QMPSF).
      Array-based comparative genomic hybridization (array CGH) analysis was performed
      using Agilent Human Genome 244K Microarrays to further map the genomic
      rearrangements. RESULTS: We identified 3 different deletions in 3 unrelated
      families: 1 in KCNQ1 and 2 involving KCNH2. We showed in the largest family that
      the deletion involving KCNH2 is fully penetrant and segregates with the long QT
      phenotype in 7 affected members. CONCLUSIONS: Our study demonstrates that CNVs in
      KCNQ1 and KCNH2 explain around 3% of LQTS in patients with no point mutation in
      these genes. This percentage is likely higher than the frequency of point
      mutations in ANKB, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP9, and SNTA1
      together. Thus, we propose that CNV screening in KCNQ1 and KCNH2 may be performed
      routinely in LQTS patients.

PMID- 21185500
TI  - DNA structural variants as genetic risk factors for the long QT syndrome.

PMID- 21185502
TI  - Genetic testing in subjects with no clinical abnormality: the tip of a huge
      iceberg.

PMID- 21185501
TI  - Risk for life-threatening cardiac events in patients with genotype-confirmed long
      QT syndrome and normal-range corrected QT intervals.
AB  - OBJECTIVES: This study was designed to assess the clinical course and to identify
      risk factors for life-threatening events in patients with long-QT syndrome (LQTS)
      with normal corrected QT (QTc) intervals. BACKGROUND: Current data regarding the
      outcome of patients with concealed LQTS are limited. METHODS: Clinical and
      genetic risk factors for aborted cardiac arrest (ACA) or sudden cardiac death
      (SCD) from birth through age 40 years were examined in 3,386 genotyped subjects
      from 7 multinational LQTS registries, categorized as LQTS with normal-range QTc
      (<= 440 ms [n = 469]), LQTS with prolonged QTc interval (> 440 ms [n = 1,392]),
      and unaffected family members (genotyped negative with <= 440 ms [n = 1,525]).
      RESULTS: The cumulative probability of ACA or SCD in patients with LQTS with
      normal-range QTc intervals (4%) was significantly lower than in those with
      prolonged QTc intervals (15%) (p < 0.001) but higher than in unaffected family
      members (0.4%) (p < 0.001). Risk factors ACA or SCD in patients with normal-range
      QTc intervals included mutation characteristics (transmembrane-missense vs.
      nontransmembrane or nonmissense mutations: hazard ratio: 6.32; p = 0.006) and the
      LQTS genotypes (LQTS type 1:LQTS type 2, hazard ratio: 9.88; p = 0.03; LQTS type
      3:LQTS type 2, hazard ratio: 8.04; p = 0.07), whereas clinical factors, including
      sex and QTc duration, were associated with a significant increase in the risk for
      ACA or SCD only in patients with prolonged QTc intervals (female age > 13 years,
      hazard ratio: 1.90; p = 0.002; QTc duration, 8% risk increase per 10-ms
      increment; p = 0.002). CONCLUSIONS: Genotype-confirmed patients with concealed
      LQTS make up about 25% of the at-risk LQTS population. Genetic data, including
      information regarding mutation characteristics and the LQTS genotype, identify
      increased risk for ACA or SCD in this overall lower risk LQTS subgroup.

PMID- 21185504
TI  - High-resolution magnetic resonance myocardial perfusion imaging at 3.0-Tesla to
      detect hemodynamically significant coronary stenoses as determined by fractional
      flow reserve.
AB  - OBJECTIVES: The objective of this study was to compare visual and quantitative
      analysis of high spatial resolution cardiac magnetic resonance (CMR) perfusion at
      3.0-T against invasively determined fractional flow reserve (FFR). BACKGROUND:
      High spatial resolution CMR myocardial perfusion imaging for the detection of
      coronary artery disease (CAD) has recently been proposed but requires further
      clinical validation. METHODS: Forty-two patients (33 men, age 57.4 +/- 9.6 years)
      with known or suspected CAD underwent rest and adenosine-stress k-space and time
      sensitivity encoding accelerated perfusion CMR at 3.0-T achieving in-plane
      spatial resolution of 1.2 * 1.2 mm(2). The FFR was measured in all vessels with
      >50% severity stenosis. Fractional flow reserve <0.75 was considered
      hemodynamically significant. Two blinded observers visually interpreted the CMR
      data. Separately, myocardial perfusion reserve (MPR) was estimated using Fermi
      constrained deconvolution. RESULTS: Of 126 coronary vessels, 52 underwent
      pressure wire assessment. Of these, 27 lesions had an FFR <0.75. Sensitivity and
      specificity of visual CMR analysis to detect stenoses at a threshold of FFR <0.75
      were 0.82 and 0.94 (p < 0.0001), respectively, with an area under the receiver
      operator characteristic curve of 0.92 (p < 0.0001). From quantitative analysis,
      the optimum MPR to detect such lesions was 1.58, with a sensitivity of 0.80,
      specificity of 0.89 (p < 0.0001), and area under the curve of 0.89 (p < 0.0001).
      CONCLUSIONS: High-resolution CMR MPR at 3.0-T can be used to detect flow-limiting
      CAD as defined by FFR, using both visual and quantitative analyses.

PMID- 21185503
TI  - Prediction of cardiovascular events in statin-treated stable coronary patients by
      lipid and nonlipid biomarkers.
AB  - OBJECTIVES: The aim of this study was to investigate the relationship between
      lipid and nonlipid biomarker levels achieved during statin therapy and the
      incidence of major cardiovascular events (MCVEs) in patients with stable coronary
      heart disease (CHD). BACKGROUND: Several plasma nonlipid biomarkers have been
      shown to predict MCVEs in population studies. METHODS: This is a nested case
      control study in the TNT (Treating to New Targets) study population, a randomized
      trial that compared the efficacy of high- (80 mg) versus low-dose (10 mg)
      atorvastatin for the secondary prevention of CHD. Fasting plasma levels of
      standard lipids and of 18 nonlipid biomarkers were obtained after an 8-week run
      in period on atorvastatin 10 mg and again 1 year after being randomized to 10 or
      80 mg atorvastatin in 507 patients who experienced MCVEs during the 4.9 years of
      study follow-up and in 1,020 control subjects. An MCVE was defined as CHD death;
      nonfatal, non-procedure-related myocardial infarction; resuscitated cardiac
      arrest; or fatal or nonfatal stroke. RESULTS: Low-density lipoprotein
      cholesterol, high-density lipoprotein cholesterol, and triglycerides were all
      predictive of recurrent MCVEs (p <= 0.009). Concentrations of many of the 18
      nonlipid biomarkers were lowered by atorvastatin therapy (independent of dose).
      However, almost none of the nonlipid biomarker levels, whether measured after the
      8-week run-in period or after 1 year of treatment with 10 or 80 mg atorvastatin,
      were predictive of recurrent MCVEs. CONCLUSIONS: In patients with stable CHD,
      atorvastatin improved plasma levels of an expanded panel of nonlipid biomarkers.
      However, independently of atorvastatin dose, the achieved levels of the vast
      majority of nonlipid biomarkers did not predict MCVEs. (A Study to Determine the
      Degree of Additional Reduction in CV Risk in Lowering LDL Below Minimum Target
      Levels [TNT]; NCT00327691).

PMID- 21185505
TI  - Cardiac effects of antiretroviral therapy in HIV-negative infants born to HIV
      positive mothers: NHLBI CHAART-1 (National Heart, Lung, and Blood Institute
      Cardiovascular Status of HAART Therapy in HIV-Exposed Infants and Children cohort
      study).
AB  - OBJECTIVES: The aim of this study was to investigate the possible effects of
      antiretroviral therapy (ART) in utero on cardiac development and function in
      human immunodeficiency virus (HIV)-negative children. BACKGROUND: ART reduces
      vertical HIV transmission. Long-term cardiotoxicity after in utero exposure to
      ART is unknown in children but has occurred in young animals. METHODS: Using a
      prospective multisite cohort study design, echocardiograms taken between birth
      and 24 months were compared in 2 groups of HIV-negative infants of HIV-positive
      mothers: 136 infants exposed to ART (ART+) and 216 unexposed infants (ART-).
      RESULTS: Mean left ventricular (LV) mass z-scores were consistently lower in ART+
      girls than in ART- girls: differences in mean z-scores were -0.46 at birth (p =
      0.005), -1.02 at 6 months (p < 0.001), -0.74 at 12 months (p < 0.001), and -0.79
      at 24 months (p < 0.001). Corresponding differences in z-scores for boys were
      smaller: 0.13 at 1 month (p = 0.42), -0.44 at 6 months (p = 0.01), -0.15 at 12
      months (p = 0.37), and -0.21 at 24 months (p = 0.21). Septal wall thickness and
      LV dimension were smaller than expected in ART+ infants, but LV contractility was
      consistently about 1 SD higher at all ages (p < 0.001). In ART+ infants, LV
      fractional shortening was higher than in ART- infants; girls showed a greater
      difference. CONCLUSIONS: Fetal exposure to ART is associated with reduced LV
      mass, LV dimension, and septal wall thickness z-scores and increased LV
      fractional shortening and contractility up to age 2 years. These effects are more
      pronounced in girls than in boys. Fetal ART exposure may impair myocardial growth
      while improving depressed LV function.

PMID- 21185506
TI  - Noncoronary cardiac abnormalities are associated with coronary artery dilation
      and with laboratory inflammatory markers in acute Kawasaki disease.
AB  - OBJECTIVES: We explored the association of noncoronary cardiac abnormalities with
      coronary artery dilation and with laboratory inflammatory markers early after
      Kawasaki disease (KD) diagnosis. BACKGROUND: Left ventricular (LV) dysfunction,
      mitral regurgitation (MR), and aortic root dilation occur early after diagnosis;
      their associations with coronary artery dilation and inflammatory markers have
      not been well-described. METHODS: Centrally interpreted echocardiograms were
      obtained at KD diagnosis and 1 and 5 weeks after diagnosis on 198 subjects in the
      National Institutes of Health-sponsored Pediatric Heart Network KD pulsed steroid
      trial. Regression models were constructed to investigate the relationships among
      early LV dysfunction, MR, and aortic root dilation with coronary artery dilation
      and laboratory inflammatory markers. RESULTS: At diagnosis, LV systolic
      dysfunction was present in 20% of subjects and was associated with coronary
      artery dilation, seen in 29% (p = 0.004). Although LV dysfunction improved
      rapidly, LV dysfunction at diagnosis predicted greater odds of coronary artery
      dilation at 1 and 5 weeks after diagnosis (5-week odds ratio: 2.7, 95% confidence
      interval: 1.2 to 6.3). At diagnosis, MR was present in 27% of subjects and aortic
      root dilation was present in 8%; each was associated with larger coronary artery
      size at diagnosis. Left ventricular dysfunction was associated with higher
      erythrocyte sedimentation rate and, at diagnosis only, lower serum albumin; MR
      was associated with higher erythrocyte sedimentation rate and lower albumin at
      all times. Aortic root size had little association with inflammatory markers.
      CONCLUSIONS: Noncoronary cardiac abnormalities are associated with coronary
      artery dilation and laboratory evidence of inflammation in the first 5 weeks
      after KD, suggesting a shared inflammatory mechanism. (Trial of Pulse Steroid
      Therapy in Kawasaki Disease [A Trial Conducted by the Pediatric Heart Network];
      NCT00132080).

PMID- 21185507
TI  - Coadministration of atorvastatin prevents nitroglycerin-induced endothelial
      dysfunction and nitrate tolerance in healthy humans.
AB  - OBJECTIVES: We aimed to assess whether concurrent administration of atorvastatin
      would modify the development of tolerance and endothelial dysfunction associated
      with sustained nitroglycerin (GTN) therapy in humans. BACKGROUND: Animal studies
      have demonstrated that administration of 3-hydroxy-3 methylglutaryl coenzyme A
      reductase inhibitors can protect against GTN-induced endothelial dysfunction and
      tolerance, likely through an antioxidant mechanism. METHODS: Thirty-six healthy
      male volunteers were randomized to receive continuous transdermal GTN (0.6 mg/h)
      and placebo, atorvastatin (80 mg/day) alone, or continuous transdermal GTN (0.6
      mg/h) with concurrent atorvastatin (80 mg/day), all for 7 days. On the second
      visit, forearm blood flow was measured with venous-occlusion strain gauge
      plethysmography in response to incremental infusions of acetylcholine (7.5, 15,
      and 30 MUg/min). Acetylcholine infusions were coinfused first with saline, and
      repeated during the coinfusion of vitamin C (24 mg/min). Blood pressure responses
      to sublingual GTN (400 MUg) were assessed on both visits. RESULTS: Acetylcholine
      responses in the GTN plus placebo group were significantly attenuated versus
      those in the GTN plus atorvastatin and atorvastatin groups (p < 0.01). Coinfusion
      of vitamin C completely restored acetylcholine responses in the GTN plus placebo
      group (p < 0.01 vs. saline coinfusion), but caused no change in either the
      atorvastatin or the GTN plus atorvastatin groups. Blood pressure responses to
      sublingual GTN did not significantly change between visits in subjects receiving
      GTN plus atorvastatin and atorvastatin alone, but were significantly blunted in
      the GTN plus placebo group (p < 0.05). CONCLUSIONS: The present findings
      demonstrate, for the first time in humans, that atorvastatin prevents both GTN
      induced endothelial dysfunction and nitrate tolerance, likely by counteracting
      the GTN-induced increase in oxidative stress.

PMID- 21185508
TI  - Adipokine resistin is a key player to modulate monocytes, endothelial cells, and
      smooth muscle cells, leading to progression of atherosclerosis in rabbit carotid
      artery.
AB  - OBJECTIVES: We investigated the effects of human resistin on atherosclerotic
      progression and clarified its underlying mechanisms. BACKGROUND: Resistin is an
      adipokine first identified as a mediator of insulin resistance in murine obesity
      models. But, its role in human pathology is under debate. Although a few recent
      studies suggested the relationship between resistin and atherosclerosis in
      humans, the causal relationship and underlying mechanism have not been clarified.
      METHODS: We cloned rabbit resistin, which showed 78% identity to human resistin
      at the complementary deoxyribonucleic acid level, and its expression was examined
      in 3 different atherosclerotic rabbit models. To evaluate direct role of resistin
      on atherosclerosis, collared rabbit carotid arteries were used. Histological and
      cell biologic analyses were performed. RESULTS: Rabbit resistin was expressed by
      macrophages of the plaque in the 3 different atherosclerotic models. Peri
      adventitial resistin gene transfer induced macrophage infiltration and expression
      of various inflammatory cytokines, resulting in the acceleration of plaque growth
      and destabilization. In vitro experiments elucidated that resistin increased
      monocyte-endothelial cell adhesion by upregulating very late antigen-4 on
      monocytes and their counterpart vascular cell adhesion molecule-1 on endothelial
      cells. Resistin augmented monocyte infiltration in collagen by direct
      chemoattractive effect as well as by enhancing migration toward monocyte
      chemotactic protein-1. Administration of connecting segment-1 peptide, which
      blocks very late antigen-4 * vascular cell adhesion molecule-1 interaction,
      ameliorated neointimal growth induced by resistin in vivo. CONCLUSIONS: Our
      results indicate that resistin aggravates atherosclerosis by stimulating
      monocytes, endothelial cells, and vascular smooth muscle cells to induce vascular
      inflammation. These findings provide the first insight on the causal relationship
      between resistin and atherosclerosis.

PMID- 21185509
TI  - Images in cardiology. Intermittent obstruction of a prosthetic aortic valve.

PMID- 21185510
TI  - President's page: Quality and appropriateness of care: the response to
      allegations and actions needed by the cardiovascular professional.

PMID- 21185511
TI  - Blood pressure and stroke: findings from recent trials.

PMID- 21185512
TI  - FAME and coronary stent investigations: is there a kink in the wire?

PMID- 21185515
TI  - Who are you going to believe? Adolescents and nicotine addiction.

PMID- 21185516
TI  - Growing our kids in "healthy soil": new research on environmental influences on
      children's food intake.

PMID- 21185517
TI  - Same-sex attraction and health disparities: do sexual minority youth really need
      something different for healthy development?

PMID- 21185518
TI  - Smoking-related cue-induced brain activation in adolescent light smokers.
AB  - PURPOSE: To examine using functional magnetic resonance imaging whether
      adolescents with low levels of nicotine exposure (light smokers) display neural
      activation in areas shown to be involved with addiction in response to smoking
      related stimuli. DESIGN/SETTING/PARTICIPANTS: A total of 12 adolescent light
      smokers (aged 13-17, who smoked 1-5 cigarettes per day) and 12 nonsmokers (ages
      13-17, never smoked a cigarette) from the San Francisco Bay Area underwent
      functional magnetic resonance imaging scanning. During scanning, the adolescents
      were shown photographic blocks of smoking and control cues. Smoking cues
      comprised pictures of individuals smoking cigarettes and smoking-related objects
      such as lighters and ashtrays. Neutral cues comprised images of everyday objects
      and individuals engaged in daily activities. FINDINGS: For smokers, smoking cues
      elicited greater activation than neutral cues in the mesolimbic reward circuit
      (left anterior cingulate: t = 7.04, p < .001; right hippocampus: t = 6.37, p <
      .001). We found activation from smoking cues versus neutral cues within both the
      left and right frontal medial orbital regions (t = 5.09, p < .001 and t = 3.94, p
      = .001, respectively). Nonsmokers showed no significant difference in activation
      between smoking-related cues and neutral cues. CONCLUSION: Our finding that
      smoking cues produced activation in adolescent light smokers in brain regions,
      similar to that seen in adult and teenage heavy smokers, suggests that
      adolescents exhibit heightened reactivity to smoking cues even at low levels of
      smoking. This article adds to the existing published data by suggesting that
      nicotine dependence may begin with exposure to low levels of nicotine, thus
      underscoring the need for early intervention among adolescent smokers.

PMID- 21185519
TI  - Food sold in school vending machines is associated with overall student dietary
      intake.
AB  - PURPOSE: To examine the association between food sold in school vending machines
      and the dietary behaviors of students. METHODS: The 2005-2006 U.S. Health
      Behavior in School-aged Children survey was administered to 6th to 10th graders
      and school administrators. Dietary intake in students was estimated with a brief
      food frequency measure. School administrators completed questions regarding food
      sold in vending machines. For each food intake behavior, a multilevel regression
      analysis modeled students (level 1) nested within schools (level 2), with the
      corresponding food sold in vending machines as the main predictor. Control
      variables included gender, grade, family affluence, and school poverty index.
      Analyses were conducted separately for 6th to 8th and 9th-10th grades. RESULTS:
      In all, 83% of the schools (152 schools; 5,930 students) had vending machines
      that primarily sold food of minimal nutritional values (soft drinks, chips, and
      sweets). In younger grades, availability of fruit and/or vegetables and chocolate
      and/or sweets was positively related to the corresponding food intake, with
      vending machine content and school poverty index providing an explanation for
      70.6% of between-school variation in fruit and/or vegetable consumption and 71.7%
      in sweets consumption. Among the older grades, there was no significant effect of
      food available in vending machines on reported consumption of those food.
      CONCLUSION: Vending machines are widely available in public schools in the United
      States. In younger grades, school vending machines were either positively or
      negatively related to the diets of the students, depending on what was sold in
      them. Schools are in a powerful position to influence the diets of children;
      therefore, attention to the food sold at school is necessary to try to improve
      their diets.

PMID- 21185520
TI  - The costs of food at home and away from home and consumption patterns among U.S.
      adolescents.
AB  - PURPOSE: This study examined the associations of prices of food at home
      groceries, prices of fast food away from home and the availability of food stores
      and restaurants with the number of days over the past week that adolescents
      consumed fruit and fruit juices, vegetables, meat, nonmeat protein, dairy,
      grains, and sweets. METHODS: Individual-level data on adolescents were drawn from
      the Child Development Supplement of the Panel Study of Income Dynamics combined
      at the zip code level with external economic contextual data. Multivariate
      regression analyses were used to estimate the associations between food
      consumption categories and the economic contextual factors. Regressions were also
      estimated by households' poverty status. RESULTS: Fast food and food at home
      prices were not significantly associated with any of the food consumption
      categories in the full sample. However, among poor adolescents, higher fast food
      prices were associated with higher levels of nonmeat protein consumption. Food
      store outlet availability was found to have very small significant associations
      with some food consumption categories but no significant associations were found
      for restaurant outlets. CONCLUSIONS: Food away from home prices, such as fast
      food prices and supermarket and grocery store availability, were associated with
      some food consumption categories among low-income youths and related policies
      deserve further examination.

PMID- 21185521
TI  - Comparison of teenagers' early same-sex and heterosexual behavior: UK data from
      the SHARE and RIPPLE studies.
AB  - PURPOSE: North American research finds increased sexual risk-taking among
      teenagers with same-sex partners, but understanding of underlying processes is
      limited. The research carried out in the United Kingdom compares teenagers' early
      sexual experiences according to same- or opposite-sex partner, focusing on
      unwanted sex in addition to risk-taking, and exploring underlying psychosocial
      differences. METHODS: Multivariate analyses combined self-reported data from two
      randomized control trials of school sex education programs (N = 10,250). Outcomes
      from sexually experienced teenagers (N = 3,766) were partner pressure to have
      first sex and subsequent regret, and sexual risk measures including pregnancy.
      Covariates included self-esteem, future expectations, substance use, and
      communication with mother. RESULTS: By the time of follow-up (mean age, 16), same
      sex genital contact (touching or oral or anal) was reported by 2.3% of teenagers,
      with the majority also reporting heterosexual intercourse. A total of 39%
      reported heterosexual intercourse and no same-sex genital contact. Boys were more
      likely to report partner pressure (Odds ratio [OR] = 2.56, 95% confidence
      intervals [CI] = 1.29-5.08) and regret (OR = 2.32; 95% CI = 1.39-3.86) in
      relation to first same-sex genital contact than first heterosexual intercourse,
      but girls showed no differences according to partner type. Teenagers with
      bisexual behavior reported greater pregnancy or partner pregnancy risk than
      teenagers with exclusively opposite-sex partners (girls, OR = 4.51, 95% CI = 2.35
      8.64; boys, OR = 4.43, 95% CI = 2.41-8.14), partially reduced by attitudinal and
      behavioral differences. CONCLUSIONS: This UK study confirms greater reporting of
      sexual risk-taking among teenagers with same-sex partners, and suggests that boys
      in this group are vulnerable to unwanted sex. It suggests limitations to the
      interpretation of differences, in terms of psychosocial risk factors common to
      all adolescents.

PMID- 21185522
TI  - Role modeling, risk, and resilience in California adolescents.
AB  - PURPOSE: To examine the relationship between role model presence, type of role
      model, and various health-risk and health-protective behaviors among California
      adolescents. METHODS: We used cross-sectional data on 4,010 multiethnic
      adolescents aged 12-17 years from the 2003 California Health Interview Survey, a
      population-based random-digit dial telephone survey of more than 40,000
      California households. The survey, conducted every other year since 2001,
      collects extensive demographic, health, and health-related information. RESULTS:
      Fifty-nine percent of adolescents identified a role model. Affluent teens were
      more likely to have a role model than lower income teens. Role models were
      generally of the same ethnicity and gender as the teens; ethnic congruence was
      higher among African Americans and whites than Latinos and Asians; gender
      congruence was higher among males. Type of role model was significantly
      associated with health-related behaviors. Identification of a teacher was
      strongly associated with positive health behaviors. Correlations with health
      promoting behaviors were generally smaller in magnitude but consistently positive
      among family member and athlete role models. Peer or entertainer role models were
      associated with health-risk behaviors. CONCLUSION: Not only role model presence
      but also the type of role model is an important predictor of adolescent health
      related behaviors. Our findings have implications for designing youth targeted
      interventions and policies involving role models.

PMID- 21185523
TI  - Motivation and body-related factors as discriminators of change in adolescents'
      exercise behavior profiles.
AB  - PURPOSE: A prospective study was conducted to explore the relative contributions
      of weight-related self-perceptions and exercise-related motivation variables in
      predicting change in leisure-time exercise within a sample of adolescents in the
      United Kingdom. METHODS: A cohort of 310 adolescents (51% male, Mean age = 14.08
      +/- .32 years at baseline) was classified into four groups on the basis of
      reported change in leisure-time exercise over 10-months: those who maintain, drop
      out from exercise, take up exercise, and those who were continually inactive.
      Discriminant function analyses were conducted to predict group membership from
      adolescents' profiles of motivational and weight-related perceptions at baseline.
      RESULTS: For boys, the first discriminant function (DF1) revealed that exercise
      maintainers reported higher identified regulation, introjected regulation,
      competence, relatedness, and body satisfaction than all other groups (between
      group R(2) = .45). DF2 was more indicative of current exercise levels than
      change, indicating higher intrinsic motivation and lower amotivation for both
      active groups at baseline (between-group R(2) = .40). In girls, DF1 showed that
      exercise maintainers reported higher intrinsic motivation, identified regulation,
      autonomy, competence, relatedness, and lower external regulation than all other
      groups (between-group R(2) = .58). DF2 indicated that higher body mass index, and
      perceiving greater pressure to lose weight positively predicted drop out, and
      negatively predicted exercise uptake (between-group R(2) = .26). CONCLUSIONS:
      Fostering autonomous (self-determined) motivation seems a key determinant to
      maintaining leisure-time exercise for both boys and girls. Additionally, reducing
      perceptions of pressure to lose weight and promoting positive interactions with
      others during exercise may be particularly useful to prevent dropout in girls.

PMID- 21185524
TI  - Environmental influences on young adult weight gain: evidence from a natural
      experiment.
AB  - OBJECTIVES: This study investigated the importance of environmental influences in
      explaining weight gain and related behaviors among freshman college students.
      METHODS: We exploited a natural experiment that takes place on most college
      campuses in the United States--randomized dormitory assignments. We estimated the
      effects of living in dormitories with varying physical environment
      characteristics on weight gain and related behaviors (daily number of meals and
      snacks, weekly frequency of exercise) among randomly assigned freshman students.
      RESULTS: We found strong evidence linking weight and related behaviors to
      individual dormitories, as well as to specific characteristics of the
      dormitories. On average, students assigned to dormitories with on-site dining
      halls gained more weight and exhibited more behaviors consistent with weight gain
      during the freshman year as compared with students not assigned to such
      dormitories. Females in such dormitories weighed .85 kg (p = .03) more and
      exercised 1.43 (p < .01) times fewer; males consumed .22 (p = .02) more meals and
      .38 (p = .01) more snacks. For female students, closer proximity of the dormitory
      to a campus gym led to more frequent exercise (.54, p = .03), whereas living
      closer to central campus reduced exercise (-.97, p = .01). CONCLUSIONS: Using a
      natural experiment to deal with the potential endogeneity of the living
      environment, this study found that the physical environment affects both
      students' weight changes and weight-related behaviors.

PMID- 21185525
TI  - Breathing awareness meditation and LifeSkills Training programs influence upon
      ambulatory blood pressure and sodium excretion among African American
      adolescents.
AB  - PURPOSE: To evaluate the effect of breathing awareness meditation (BAM), Botvin
      LifeSkills Training (LST), and health education control (HEC) on ambulatory blood
      pressure and sodium excretion in African American adolescents. METHODS: Following
      3 consecutive days of systolic blood pressure (SBP) screenings, 166 eligible
      participants (i.e., SBP >50th-95th percentile) were randomized by school to
      either BAM (n = 53), LST (n = 69), or HEC (n = 44). In-school intervention
      sessions were administered for 3 months by health education teachers. Before and
      after the intervention, overnight urine samples and 24-hour ambulatory SBP,
      diastolic blood pressure, and heart rate were obtained. RESULTS: Significant
      group differences were found for changes in overnight SBP and SBP, diastolic
      blood pressure, and heart rate over the 24-hour period and during school hours.
      The BAM treatment exhibited the greatest overall decreases on these measures
      (Bonferroni adjusted, ps < .05). For example, for school-time SBP, BAM showed a
      change of -3.7 mmHg compared with no change for LST and a change of -.1 mmHg for
      HEC. There was a nonsignificant trend for overnight urinary sodium excretion (p =
      .07), with the BAM group displaying a reduction of -.92 +/- 1.1 mEq/hr compared
      with increases of .89 +/- 1.2 mEq/hr for LST and .58 +/- .9 mEq/hr for HEC group.
      CONCLUSION: BAM appears to improve hemodynamic function and may affect sodium
      handling among African American adolescents who are at increased risk for
      development of cardiovascular disease.

PMID- 21185526
TI  - Sensation seeking, risk behaviors, and alcohol consumption among Mexican origin
      youth.
AB  - PURPOSE: To examine factors associated with ever use of alcohol among Mexican
      origin youth. METHODS: Using a prospective study design, we followed 1,053
      Mexican origin adolescents. Participants completed two surveys in their homes and
      three follow-up telephone interviews, every 6-8 months, in between. The second
      home survey was completed 30 months (SD = 4.8 months) after baseline.
      Acculturation, subjective social status, and family cohesion were assessed at
      baseline and final home visit. Ever drinking, risk behaviors, and sensation
      seeking tendencies were assessed at the final home visit only. RESULTS: Overall,
      30% of the study participants reported ever drinking alcohol. Multivariate models
      revealed that being female, increasing age, lower levels of acculturation, family
      cohesion and subjective social status, higher sensation-seeking tendencies, and
      concomitantly engaging in three or four other risk behaviors were associated with
      ever drinking. Also, social disinhibition, an aspect of sensation seeking,
      mediated the relationship between engaging in other risk behaviors and alcohol
      use. This is consistent with previous research, suggesting that social
      disinhibition is a common factor that underlies the use of alcohol, tobacco,
      illicit drugs, and other problem behaviors. CONCLUSIONS: The results of this
      study support taking a family-based approach to prevention that includes
      discussion of other risk behaviors, especially smoking, among Mexican origin
      youth. In addition, tailoring programs by gender, directly addressing how changes
      in social norms resulting from acculturation can affect a youth's decision to
      drink alcohol and underlying gender-based differences in why youth drink could
      improve the efficacy of preventive interventions.

PMID- 21185527
TI  - Can the gateway hypothesis, the common liability model and/or, the route of
      administration model predict initiation of cannabis use during adolescence? A
      survival analysis--the TRAILS study.
AB  - PURPOSE: There is substantial research linking tobacco and alcohol use to
      subsequent cannabis use, yet the specificity of this relationship is still under
      debate. The aim of this study was to examine which substance use model--the
      gateway hypothesis, the common liability (CL) model and/or the route of
      administration model--best explains the relationship between early onset of
      tobacco and alcohol use and subsequent cannabis use initiation. METHODS: We used
      data from 2,113 (51% female) Dutch adolescents who participated in three
      consecutive assessment waves (mean age: 11.09, 13.56, and 16.27 years,
      respectively) of the TRacking Adolescents' Individual Lives Survey study.
      (Pre)adolescent cannabis, tobacco and alcohol use was assessed using the Youth
      Self-Report and a TRacking Adolescents' Individual Lives Survey developed
      questionnaire. RESULTS: We found that, during adolescence, early onset of tobacco
      use does not pose a significantly higher risk of initiating cannabis use than
      early onset alcohol use. Therefore, we can rule out the route of administration
      model. Moreover, we found that adolescents who reported early onset comorbid use
      of both tobacco and alcohol have a higher likelihood to initiate cannabis use
      than adolescents who have tried either tobacco or alcohol. The gateway hypothesis
      is not broad enough to explain this finding. Therefore, the CL model best
      predicts our findings. CONCLUSION: Future research on adolescent cannabis
      initiation should focus on testing the robustness of the CL model. Furthermore,
      identifying adolescents who use both tobacco and alcohol, before the age of 13,
      may help to curtail the onset of cannabis use.

PMID- 21185528
TI  - Scaling up adolescent sexual and reproductive health interventions through
      existing government systems? A detailed process evaluation of a school-based
      intervention in Mwanza region in the northwest of Tanzania.
AB  - PURPOSE: There is little evidence from the developing world of the effect of
      scale-up on model adolescent sexual and reproductive health (ASRH) programmes. In
      this article, we document the effect of scaling up a school-based intervention
      (MEMA kwa Vijana) from 62 to 649 schools on the coverage and quality of
      implementation. METHODS: Observations of 1,111 students' exercise books, 11 ASRH
      sessions, and 19 peer-assistant role plays were supplemented with interviews with
      47 ASRH-trained teachers, to assess the coverage and quality of ASRH sessions in
      schools. RESULTS: Despite various modifications, the 10-fold scale-up achieved
      high coverage. A total of 89% (989) of exercise books contained some MEMA kwa
      Vijana 2 notes. Teachers were enthusiastic and interacted well with students.
      Students enjoyed the sessions and scripted role plays strengthened participation.
      Coverage of the biological topics was higher than the psycho-social sessions. The
      scale-up was facilitated by the structured nature of the intervention and the
      examined status of some topics. However, delays in the training, teacher
      turnover, and a lack of incentive for teaching additional activities were
      barriers to implementation. CONCLUSIONS: High coverage of participatory school
      based reproductive health interventions can be maintained during scale-up.
      However, this is likely to be associated with significant changes in programme
      content and delivery. A greater emphasis should be placed on improving teachers'
      capacity to teach more complex-skills-related activities. Future intervention
      scale-up should also include an increased level of supervision and may be
      strengthened by underpinning from national level directives and inclusion of
      behavioral topics in national examinations.

PMID- 21185529
TI  - Variation in sexual behaviors in a cohort of adolescent females: the role of
      personal, perceived peer, and perceived family attitudes.
AB  - PURPOSE: Little is known about how adolescent sexual behaviors develop and the
      influence of personal or perceived social attitudes. We sought to describe how
      personal, perceived peer, and perceived family attitudes toward adolescent sexual
      activity influence sexual behaviors of adolescent females' over time. METHODS:
      Between the years of 1999 and 2006, 358 English-speaking female adolescents, aged
      14-17 years, were recruited from three urban adolescent clinics. Participants
      completed quarterly and annual questionnaires over a span of 4 years. Primary
      outcomes included engagement in any of the following eight sexual behaviors:
      kissing, having breasts touched, having genitals touched, touching partners'
      genitals, oral giving, oral receiving, anal, or vaginal sex. Three attitudinal
      scales assessed personal importance of abstinence, perceived peer beliefs about
      when to have sex, and perceived family beliefs that adolescent sex is negative.
      We used generalized estimating equations to identify predictors of each sexual
      behavior and compared whether personal, perceived peer, or perceived family
      attitudes predicted sexual behaviors over time. RESULTS: The odds of reporting
      each sexual behavior increased with age but were lower among those whose personal
      or perceived family attitudes were less positive. Participants' personal
      attitudes toward adolescent sex were the strongest predictor of engagement in all
      eight sexual behaviors even after controlling for perceived peer and perceived
      family attitudes. CONCLUSIONS: Female adolescent's personal attitudes toward
      abstinence appear to be the strongest predictor of engagement in a variety of
      sexual behaviors. Efforts to influence adolescent attitudes toward abstinence may
      be an important approach to reducing sexual behaviors that increase the risk of
      pregnancy and sexually transmitted infections.

PMID- 21185531
TI  - HIV-infected adolescents: relationship between atazanavir plasma levels and
      bilirubin concentrations.
AB  - The use of atazanavir (ATV) in adolescents infected with human immunodeficiency
      virus was analyzed in this study. ATV morning plasma concentrations were
      determined during regular visits to the outpatient department. Results showed
      that bilirubin levels were higher among patients with higher ATV plasma
      concentrations (p = .018). Monitoring plasma levels of ATV could avoid toxicity
      in these patients.

PMID- 21185532
TI  - High prevalence of Pneumocystis jiroveci colonization among young HIV-infected
      patients.
AB  - BACKGROUND: Pneumocystis colonization in young HIV-infected patients has been
      poorly studied. The aim of this study was to analyze the prevalence of P jiroveci
      colonization in a cohort of young HIV-infected patients. MATERIAL AND METHODS: We
      designed a basal cross-sectional study in 20 young HIV-infected patients to
      determine the prevalence of P jiroveci colonization in oropharyngeal wash samples
      studied by nested polymerase chain reaction (PCR). Subsequently, patients were
      followed up during 50 weeks to observe the development of Pneumocystis pneumonia
      (PCP). RESULTS: P jiroveci colonization was detected in eight (40%) of the 20
      oropharyngeal wash samples. Genotype 85C/248C was the most frequent. After 50
      weeks of follow-up, one colonized patient with advanced immunodepression
      developed PCP. CONCLUSIONS: We have found a high prevalence of P jiroveci
      colonization in young HIV-infected patients with a major prevalence of genotype 1
      (85C/248C). Further studies are necessary to clarify if Pneumocystis colonization
      could be a potential risk factor of developing PCP in young HIV infected
      patients.

PMID- 21185530
TI  - Transmitted HIV-1 drug resistance among young men of color who have sex with men:
      a multicenter cohort analysis.
AB  - BACKGROUND: Given the elevated potential for primary or transmitted drug
      resistance (TDR) among newly HIV-infected individuals, there is a need for a
      deeper understanding of the baseline resistance patterns present in young men of
      color who have sex with men. METHODS: Genotypic data were collected for
      participants aged 13-24 who were enrolled from seven sites. Univariate and
      bivariate methods were used to describe the prevalence of TDR and characteristics
      associated with TDR. RESULTS: Of the 296 individuals participating in the
      substudy, 145 (49%) had baseline genotypes. The majority of the individuals were
      African American (65%) and gay-identified (70%). There was significant variation
      in genotype availability by site (p < .001). Major surveillance drug resistance
      mutations were present in 28 subjects (19.3%); the majority were non-nucleoside
      reverse transcriptase inhibitor mutations (12.4%). Subjects with TDR were less
      likely to have used alcohol on 1 or more days in the prior 2 weeks. Location was
      not associated with acquisition of TDR. CONCLUSIONS: There was a high rate of TDR
      in a geographically and racially diverse sample of HIV-infected young men of
      color who have sex with men. This represents a serious public health concern
      given the young age of this sample and the potential need for long-term
      antiretroviral therapy. These findings underscore the critical roles of both
      early case identification and secondary prevention.

PMID- 21185533
TI  - The utility of keg registration laws: a cross-sectional study.
AB  - PURPOSE: Many states have implemented keg registration policies to reduce
      adolescent binge drinking and related consequences. We examined the association
      between the strength and comprehensiveness of these policies and measures of beer
      consumption in the general population and adolescent binge drinking, as well as
      drinking and driving. METHODS: Data concerning the presence and stringency of the
      states' keg registration laws were secured from the Alcohol Policy Information
      System. Keg law ratings for each state were correlated with its (1) beer
      consumption per capita, as well as the 30-day prevalence of the following: (2)
      adolescent binge drinking, (3) adolescents who drive after drinking, and (4)
      adolescents who ride with a driver who has been drinking, as assessed by the
      Youth Risk Behavior Survey. RESULTS: As hypothesized, the stringency and
      comprehensiveness of state level keg registration laws were moderately (-.31 to 
      .41) and negatively associated with each of these outcomes. However, these
      relationships largely attenuated when controlling for per capita beer sales.
      CONCLUSIONS: Longitudinal research is needed to examine the relationships between
      keg registration policies and levels of adolescent alcohol consumption, hazardous
      drinking, and driving after drinking.

PMID- 21185535
TI  - How adolescents use SMS (short message service) to micro-coordinate contact with
      youth mental health outreach services.
AB  - BACKGROUND: Mobile phones play a central role in the lives of young people and
      are being increasingly recognized as valuable tools in health care. However,
      there is a paucity of studies exploring the use of mobile phones in youth
      outreach mental health services. Our outreach team's experience is that enabling
      youth to access their therapist directly through mobile phone improves engagement
      and retention, and short message service (SMS) in particular, is a useful tool
      for coordinating appointments. The purpose of this study was to audit the content
      of SMS exchanges between therapists and clients and to investigate the extent of
      inappropriate SMS use. METHOD: An audit of SMS messages sent and received from an
      outreach youth mental health service was conducted over a 7-month period.
      RESULTS: The majority of SMS traffic sent to and received from clients was micro
      coordinating face-to-face-meetings (76% and 61%, respectively), reflecting a
      practical real-time use of SMS. Only a small proportion of the client use of SMS
      was classified as inappropriate (2%). CONCLUSIONS: The results demonstrate that
      mobile phones and SMS can be used as a safe, practical way of maintaining contact
      and coordinating meetings within a youth outreach service.

PMID- 21185536
TI  - Human ultraweak photon emission and the yin yang concept of Chinese medicine.
AB  - The relationship between connective tissue and meridian function is discussed in
      terms of energy transmission. The network of hydrogen-bonded water molecules
      interspersed within the collagen fibrillar matrix is especially significant for
      both the sensitivity of connective tissue to weak signals of mechanical pressure,
      heat, or electricity and the electrical intercommunication that may correlate
      with the meridian acupuncture system. Special electromagnetic properties of
      connective tissue have similar collective properties of ultraweak photon
      emission. A relationship between ultraweak photon emission and yin yang dynamics
      is based on three types of ultraweak photon emission studies, focusing on diurnal
      and annual dynamics, diseased states, and acupuncture points. A novel concept
      explains the functional (health) integrity of physiologic systems in relation to
      the left-right balance in ultraweak photon emission by pointing to, (1) balanced
      corticoneuromusculoskeletal activities and triboluminescent aspects of ultraweak
      photon emission by skeletal structures, and (2) local fine-tuning in oxygen
      supply and the formation of radical oxygen species. This approach offers testable
      hypotheses for further validation utilizing a combination of human photon
      recording techniques and specialized metabolomics for the estimation of organ
      specific oxidative states.

PMID- 21185534
TI  - Disordered weight control behaviors in early adolescent boys and girls of color:
      an under-recognized factor in the epidemic of childhood overweight.
AB  - OBJECTIVES: Ethnic disparities in childhood overweight are well-documented. In
      addition, disordered weight control behaviors (DWCB) have been linked to
      overweight and weight gain in multiple ways, but little is known about DWCB in
      youth of color, especially boys. We examined the distribution and determinants of
      ethnic and gender disparities in DWCB in early adolescents. METHODS: In fall
      2005, 47 Massachusetts middle schools participating in the Healthy Choices
      overweight prevention study administered a self-report baseline survey assessing
      student sociodemographics, height, weight, and DWCB (vomiting or use of laxatives
      or diet pills in the past month to control weight). Data from 16,978 girls and
      boys were used in multivariate logistic regression models to estimate the odds of
      DWCB in youth of color compared with their white peers, controlling for
      individual- and school-level factors. RESULTS: Among white youth, 2.7% of girls
      and 2.3% of boys reported DWCB. The odds of DWCB were elevated 2-10 times in most
      ethnic groups relative to whites. Disparities were attenuated but persisted after
      controlling for multiple individual- and school-level factors. CONCLUSIONS:
      Ethnic disparities in DWCB must be considered in efforts to address the epidemic
      of childhood overweight.

PMID- 21185537
TI  - Putative primo-vascular system in mesentery of rats.
AB  - Primo-vessels have been observed in the rat abdominal cavity as floating thread
      like structures on and not adhering to fascia-wrapped internal organs. To date
      their presence, locations, and lengths have been irregular and unpredictable, and
      their identification not regularly repeatable, thus they have remained a nagging
      enigma in primo-vascular system research for several years. In this work,
      locations were found where primo-vessels were regularly present and observed
      repeatedly. These vessels were not floating or freely movable but lay in a
      regular position in the mesentery in the abdominal cavity of the rat, being
      observed between the cecum and small intestine and between the colon and
      mesentery root. The difference between a lymph vessel and a primo-vessel is
      described in anatomical and histological aspects. In addition, trypan blue was
      found to enter primo-vessels through the surrounding membranes and filled spaces
      between fibers comprising the primo-vessels. It is conjectured that the
      previously observed floating primo-vessels had anomalously and irregularly
      emerged, for some unknown physiological reasons, from primo-vessels normally
      located in the fascia-like mesentery.

PMID- 21185538
TI  - Viability assessment of primo-node slices from organ surface primo-vascular
      tissues in rats.
AB  - The primo-vascular system is a novel thread-like structure which is recently
      rediscovered, but its cellular properties are largely unknown. In this study, a
      slice preparation for primo-nodes was developed to facilitate study of the
      cellular properties of primo-node cells in vitro. Slices (4-8 slices; 200 MUm
      thick) were sectioned from single primo-nodes collected from the abdominal organ
      surface of rats and incubated in oxygenated Krebs solution at 25 degrees C or 31
      degrees C for up to 7 hours. Trypan blue staining and whole-cell patch-clamp
      recordings were performed to estimate the viability of cells in the slices.
      Viability was largely maintained during the first 3 hours, but subsequently
      decreased (from 80% to 21%, p < 0.001). In addition, the viability of slices
      incubated at 31 degrees C was higher than those incubated at 25 degrees C (80%vs.
      47%, p < 0.001). In whole-cell patch-clamp experiments, high resistance seals
      readily formed and primo-node cells showed a mean resting membrane potential (-38
      mV) comparable to that recorded with sharp electrodes and outwardly-rectifying
      current-voltage relationships. The results show that the primo-node slices
      developed in this study maintained viability for up to 4 hours in vitro.

PMID- 21185539
TI  - Meridian electrical potential response to acupuncture stimulation between
      operator and subject.
AB  - The human body has a symmetric structure and maintains a physiological balance
      through the harmony of yin and yang. One of the fundamental principles of
      acupuncture is that unbalanced or abnormal bioenergetic conditions on the left
      and right meridians may be restored to a balanced, normal condition by
      acupuncture therapy. In this study, the electrical potential along the stomach
      meridian was measured to investigate the bioenergy consensus between the operator
      and subject during acupuncture stimulation, and the acupuncture response on
      opposite meridians was investigated by comparing the electric potential on the
      left and right stomach meridian during stimulation of the left side stomach
      meridian-36. When meridian electrical potential was simultaneously measured in
      both the operator and subject, opposite polarities were observed, which might
      indicate the transfer of bioenergy between operator and subject. In addition, the
      meridian electrical potentials of the subjects' left and right stomach meridians
      were also always of opposite polarity and presented three different signal
      patterns, which might have represented the condition of the associated meridian.

PMID- 21185540
TI  - Violet laser acupuncture--part 1: Effects on brain circulation.
AB  - Violet laser acupuncture using a wavelength of 405 nm has been investigated in
      only a few scientific studies. The aim of this study was to provide selective
      evidence of a specific effect of violet laser acupuncture on mean cerebral blood
      flow velocity using a Doppler ultrasound technique. A transcranial Doppler
      sonography construction was developed especially for this study to monitor blood
      flow profiles in the basilar and middle cerebral arteries simultaneously and
      continuously. The acupuncture point Dazhui on the upper back was tested in a
      controlled study with 10 healthy volunteers (24.9 +/- 3.3 years, mean age +/- SD;
      5 females, 5 males). In addition to an on/off-effect, violet laser stimulation
      increased the blood flow velocity in the basilar artery significantly (p < 0.001)
      compared with the reference interval before laser acupuncture. In the middle
      cerebral artery, only minimal, nonsignificant changes in blood flow velocity were
      seen. Metal needle acupuncture at the same point intensified the effects;
      however, blood flow profiles did not change significantly during and after
      stimulation with a deactivated violet laser.

PMID- 21185541
TI  - Acupuncture for treating temporomandibular disorder: retrospective study on
      safety and efficacy.
AB  - This study aimed to retrospectively examine the efficacy and safety of
      acupuncture for the relief of pain originating from temporomandibular joint
      disorder and trigeminal neuralgia. Participants included patients suffering from
      trigeminal neuralgia or temporomandibular disorder with osseous pathology ruled
      out by panoramic X-rays. Participants received a series of 8-10 weekly
      acupuncture treatments and rated their pain via a visual analogue scale. From
      assessment of a total of 39 patients, analysis of pain severity before and after
      treatment showed that acupuncture intervention was highly beneficial for patients
      with temporomandibular joint disorder (88.6%, p < 0.01), compared with patients
      with trigeminal neuralgia in which there was only a minor effect (25%). The data
      also demonstrated that acupuncture was both efficacious in acute patients (91%, p
      < 0.01) and chronic patients (70%, p < 0.05) and elicited no side effects during
      the course of treatment. Acupuncture treatment was a safe and efficient
      methodology for relieving the pain of patients suffering from temporomandibular
      disorder with no detectable osseous joint component. Based on these results, a
      randomized clinical trial is being initiated at the Stomatologic Clinic at the
      Tel Aviv Sourasky Medical Center to assess the role of acupuncture in treating
      temporomandibular joint disorder.

PMID- 21185542
TI  - Evaluation of Antioxidant Potential of Melanthera scandens.
AB  - A methanol extract of dried leaves of Melanthera scandens was examined for
      antioxidant activities using a variety of assays, including 1-diphenyl-2
      picrylhydrazyl (DPPH) radical scavenging, reducing power, ferrous chelating, and
      ferric thiocyanate methods with ascorbic acid and EDTA as positive controls. The
      extract showed noticeable activities in most of these in vitro tests. The amount
      of phenolic compounds in the extract expressed in gallic acid equivalent was
      found to be 52.8 mg/g. The extract demonstrated inhibition of linoleic acid lipid
      peroxidation, active reducing power, and DPPH radical scavenging activities which
      were less than that of the positive controls. The extract also showed weaker iron
      chelating effect when compared with the EDTA positive control. The present
      results showed that M. scandens leaf extract possessed antioxidant properties and
      this plant is a potential useful source of natural antioxidants.

PMID- 21185543
TI  - In vitro pharmacodynamic profile of Loranthus ferrugineus: evidence for
      noncompetitive antagonism of norepinephrine-induced vascular contraction.
AB  - The mode by which Loranthus ferrugineus methanol extract antagonizes and/or
      modulates norepinephrine-induced vasoconstriction was investigated in rat aortic
      rings. The vascular effects of three different concentrations of this extract
      were challenged against cumulative additions of norepinephrine. Phentolamine, a
      nonselective alpha-adrenoceptor antagonist, verapamil, an L-type calcium channel
      blocker, and papaverine, a phosphodiesterase inhibitor, were used in three
      different concentrations as positive controls. Log concentration-response curves
      and double-reciprocal plots were constructed for the extract and each
      vasorelaxant. To characterize antagonism reversibility, the norepinephrine
      maximum contractile effect was examined before extract addition to the aortic
      ring chamber and after its removal. Phentolamine shifted the norepinephrine log
      concentration-response curve to the right with no significant depression in the
      maximum response. Similar to verapamil and papaverine, the extract produced a
      rightward shift in norepinephrine log concentration-response curve and a
      significant drop in maximum response. The double-reciprocal plots showed
      comparable y-intercept values for all phentolamine concentrations, a
      characteristic of competitive antagonism. In contrast, different y-intercept
      values on double-reciprocal plots were obtained for each concentration of
      extract, verapamil, and papaverine, typical of noncompetitive antagonism. The
      norepinephrine maximum contractile response was approximately similar before the
      addition of extract and after its removal. The data collectively showed that L.
      ferrugineus methanol extract exerted its vascular effect by reversible
      noncompetitive antagonism of norepinephrine-induced vasoconstriction. These
      findings add to the understanding of the cardiovascular mechanisms by which L.
      ferrugineus, a plant traditionally used for the management of hypertension,
      elicits its action.

PMID- 21185544
TI  - Antioxidant efficacy of Nasturtium officinale extracts using various in vitro
      assay systems.
AB  - Nasturtium officinale R. Br. (watercress), of the family Brassicaceae, has been
      long used as a home remedy or a medicinal plant by the people of southeastern
      Iran. The aim of this study was to investigate the antioxidant activity of N.
      officinale extract using various in vitro assay systems, including the ferric
      reducing antioxidant power and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonate)
      assays, 1,1-diphenyl-2-picrylhydrazyl, hydrogen peroxide, nitric oxide radical
      scavenging, and ferrous ion chelating activity, as well as the inhibitory effect
      on ferrous ion/ascorbate induced lipid peroxidation, in rat liver homogenate. The
      results revealed that N. officinale extract possesses potent reducing power in a
      ferric reducing antioxidant power assay, concentration-dependent scavenging
      ability on 2,2'-azinobis 3-ethylbenzothiazoline-6-sulfonate, 1,1-diphenyl-2
      picrylhydrazyl, nitric oxide radicals, and hydrogen peroxide, as well as
      chelating ability on ferrous ions. Furthermore, N. officinale extract prevented
      thiobarbituric acid reactive substances formation in ferrous ion/ascorbate
      induced lipid peroxidation in rat liver homogenate in a dose-dependent manner. In
      addition, this N. officinale extract had the phenolic and flavonoid contents of
      96.2 mg gallic acid equivalents/g dried extract and 63.2 mg catechin
      equivalents/g dried extract, respectively. The cumulative results clearly
      indicate that N. officinale extract possesses potent antioxidant properties
      probably mediated through direct trapping of free radicals, reducing power, and
      also through metal chelating. Based on its antioxidative potential, N. officinale
      extract might find applications in the prevention of free radical-related
      diseases.

PMID- 21185545
TI  - Light as a trigger and a probe of the internal dynamics of living organisms.
AB  - It has been reported that the colors perceived behind closed eyes provide an
      indication of the psychophysical state of a subject. We discuss this phenomenon
      in the light of recently developed approaches to living organisms, based on the
      interplay between matter organization, biochemistry and electrodynamics. "When
      there is no energy, there is no color, no shape, no life." Caravaggio (1571
      1610).

PMID- 21185546
TI  - Generalization of action knowledge following observational learning.
AB  - Both observational and physical practices support the acquisition of motor skill
      knowledge in the form of spatiotemporal coordination patterns. The current
      experiment examined the extent that observation and physical practice can support
      the transfer of spatiotemporal knowledge and amplitude knowledge associated with
      motor skills. Evidence from a multijoint limb task revealed that knowledge about
      spatiotemporal patterns (relative phase) acquired by observers and models can be
      generalized exceptionally well within the trained arm (right) and across to the
      untrained arm (left). Transfer of relative phase occurred even when untrained
      combinations of joint amplitudes were required. This indicates that observation
      and physical practice both lead to the development of an effector-independent
      representation of the spatiotemporal knowledge in this task. Both observers and
      models showed some transfer of the relative amplitude knowledge, with observers
      demonstrating superior transfer for both a trained and untrained-arm transfer
      test, while the models were limited to positive transfer on an untrained-arm
      transfer test. The representation of movement amplitude knowledge is effector
      independent in this task, but the use of that knowledge is constrained by the
      specific practice context and the linkage between the elbow and wrist.

PMID- 21185547
TI  - The relation between action, predictability and temporal contiguity in temporal
      binding.
AB  - Previous studies have documented a subjective temporal attraction between actions
      and their effects. This finding, named intentional binding, is thought to be the
      result of a cognitive function that links actions to their consequences. Although
      several studies have tried to outline the necessary and sufficient conditions for
      intentional binding, a quantitative comparison between the roles of temporal
      contiguity, predictability and voluntary action and the evaluation of their
      interactions is difficult due to the high variability of the temporal binding
      measurements. In the present study, we used a novel methodology to investigate
      the properties of intentional binding. Subjects judged whether an auditory
      stimulus, which could either be triggered by a voluntary finger lift or be
      presented after a visual temporal marker unrelated to any action, was presented
      synchronously with a reference stimulus. In three experiments, the
      predictability, the interval between action and consequence and the presence of
      action itself were manipulated. The results indicate that (1) action is a
      necessary condition for temporal binding; (2) a fixed interval between the two
      events is not sufficient to cause the effect and (3) only in the presence of
      voluntary action do temporal predictability and contiguity play a significant
      role in modulating the effect.These findings are discussed in the context of the
      relationship between intentional binding and temporal expectation.

PMID- 21185548
TI  - Target-flanker discriminability affects conflict size but not sustained
      suppression.
AB  - On successive trials, repetitions of irrelevant information often tend to reduce
      congruency effects as compared to alternations of irrelevant information. The
      preferred explanation for this congruency modulation is the sustained-suppression
      hypothesis, suggesting that suppression of the irrelevant information on a given
      trial perseveres into the subsequent trial. However, in contrast to the
      generality of this idea, this modulation is only stable when the irrelevant
      information contains spatial features, which coincided in the existing research
      with large conflict sizes and response conflicts. In two arrow flanker
      experiments, we investigated whether the congruency modulation depends on the
      size of the conflict, by manipulating the saliency of the target (Experiment 1)
      and the flankers (Experiment 2). Although these manipulations affected the size
      of the conflict caused by the flankers, neither experiment showed an influence of
      conflict size on the reduction of the congruency effect for repetitions as
      compared to alternation of the irrelevant flankers. We conclude that sustained
      suppression is not a consequence of large conflicts, at least if sustained
      suppression causes the congruency modulation.

PMID- 21185549
TI  - Antihypertensive peptides: production, bioavailability and incorporation into
      foods.
AB  - Bioactive food peptides are encrypted within the sequence of food proteins but
      can be released during food processing (by enzymatic hydrolysis or fermentation)
      or during gastrointestinal transit. Among bioactive food peptides, those with
      antihypertensive activity are receiving special attention due to the high
      prevalence of hypertension in the Western countries and its role in
      cardiovascular diseases. This paper reviews the current literature on
      antihypertensive food peptides, focusing on the main methodologies for their
      production, such as enzymatic hydrolysis, fermentation and the use of recombinant
      bacteria. This paper also describes the structure/activity relationship of
      angiotensin-converting enzyme (ACE)-inhibitory peptides, as well as their
      bioavailability, physiological effects demonstrated by both in vitro and in vivo
      assays, and the contribution of mechanisms of action other than ACE inhibition.
      Finally, current reported strategies for incorporation of antihypertensive
      peptides into foods and their effects on both availability and activity are
      revised in this manuscript.

PMID- 21185550
TI  - Individualized, targeted wound treatment based on the tissue bacterial level as a
      biological marker.
AB  - BACKGROUND: The use of biologic markers to aid in individualizing wound treatment
      may help improve outcomes. A biologic marker that has been demonstrated to be
      predictive of healing in both chronic and acute wounds is wound tissue bacterial
      level. The objective of this study was to determine whether tissue bacterial
      level can be used to individualize wound treatment regimens with a stem-like cell
      derived product. METHODS: Amnion-derived cellular cytokine solution (ACCS) was
      topically applied to rat chronic wounds, and healing rates were measured.
      RESULTS: Experimental wounds treated with ACCS demonstrated accelerated healing
      regardless of the tissue level of bacteria, compared with saline. As the level of
      tissue bacteria increased, the frequency of ACCS application required to obtain
      optimal results increased. CONCLUSIONS: It appears that the biologic
      characteristic of tissue bacterial level can serve as a marker to predict the
      response of open granulating wounds treated with ACCS.

PMID- 21185551
TI  - The effect of emotion regulation strategies on anger.
AB  - This study examined the effects of different emotion regulation strategies on the
      experience and expression of anger. Participants consisted of undergraduate
      students who endorsed at least a moderate level of state anger. As part of a
      laboratory experiment, they were instructed to reappraise (n = 24), suppress (n =
      24), or accept (n = 25) their anger during a frustrating task. Reappraisal was
      more effective at reducing anger than attempts to suppress or accept it.
      Furthermore, participants in the reappraisal condition persisted significantly
      longer with the frustrating task than those who were instructed to suppress or
      accept their negative feelings. These findings suggest that reappraisal
      techniques are more effective than acceptance and suppression techniques for
      modulating the experience and expression of anger.

PMID- 21185552
TI  - Eating disorder examination questionnaire and clinical impairment assessment
      questionnaire: general population and clinical norms for young adult women in
      Sweden.
AB  - Optimal use of assessment instruments for the detection and diagnosis of eating
      disorders (ED) depends on the availability of normative data. The aim of this
      work was to, for the first time, collect norms for both the Eating Disorder
      Examination Questionnaire (EDE-Q) and the newly developed Clinical Impairment
      Assessment (CIA) Scale from a general population of young women in Sweden, as
      well as from a clinical population of ED patients in Sweden. Participants were
      composed of both a randomized sample from the general population of women aged 18
      30 years (N = 760) as well as from a clinical population aged 18-66 years (N =
      2383). Data for the clinical population was extracted from the Stepwise database.
      Mean scores, standard deviations and percentile ranks for the global for the EDE
      Q (as well as its subscales) and the CIA are presented. Prevalence figures of key
      eating disorder behaviors are also reported. Comparisons are made between the
      results in the present study with other existing normative studies on the EDE-Q
      and the CIA. The present study contributes to improving the accuracy of the
      interpretation of scores of the widely used self-report measure of ED, the EDE-Q,
      and the CIA, both of which play important roles in for diagnosis, prevention and
      intervention of ED.

PMID- 21185553
TI  - Using click chemistry to access mono- and ditopic beta-cyclodextrin hosts
      substituted by chiral amino acids.
AB  - A wide range of chiral mono- and ditopic cyclodextrin-based receptors have been
      synthesized by CuI-catalyzed azide-alkyne cycloaddition starting from mono-6
      azido-beta-cyclodextrin and chiral amino acids. Of interest, microwaves proved
      very efficient to access a wide range of ditopic beta-cyclodextrin receptors with
      quantitative yields.

PMID- 21185555
TI  - Neuropsychologic profile of college students with schizotypal traits.
AB  - BACKGROUND: This study investigated the neuropsychologic functioning in
      nonclinical individuals with schizotypal traits using a comprehensive battery of
      neuropsychologic tests. METHOD: We measured the neuropsychologic functioning of
      individuals with psychometrically defined nonclinical schizotypy (n = 28) and
      healthy controls (n = 31) for verbal memory (the Korean version of the California
      Verbal Learning Test), nonverbal memory (the Rey-Osterrieth Complex Figure Test),
      executive function (the Wisconsin Card Sorting Test), and attention (the d2 Test,
      Trail Making Test, and Controlled Oral Word Association Test). RESULTS: The
      schizotypal trait group committed significantly more total and perseverative
      errors and completed fewer categories on the Wisconsin Card Sorting Test than the
      control group. Performance on the other neuropsychologic tests did not differ
      between groups. CONCLUSIONS: The nonclinical individuals with schizotypal traits
      demonstrated executive dysfunction, showing decreased ability in
      conceptualization, use of cues, and mental flexibility. Furthermore, these
      results indicate that the cognitive deficits observed in schizophrenia are also a
      characteristic of nonclinical individuals with schizotypal traits.

PMID- 21185556
TI  - The quest for the 'critical lesion site' in cognitive deficits: problems and
      perspectives.

PMID- 21185554
TI  - Taenia crassiceps infection abrogates experimental autoimmune encephalomyelitis.
AB  - Helminth infections induce strong immunoregulation that can modulate subsequent
      pathogenic challenges. Taenia crassiceps causes a chronic infection that induces
      a Th2-biased response and modulates the host cellular immune response, including
      reduced lymphoproliferation in response to mitogens, impaired antigen
      presentation and the recruitment of suppressive alternatively activated
      macrophages (AAMF). In this study, we aimed to evaluate the ability of T.
      crassiceps to reduce the severity of experimental autoimmune encephalomyelitis
      (EAE). Only 50% of T. crassiceps-infected mice displayed EAE symptoms, which were
      significantly less severe than uninfected mice. This effect was associated with
      both decreased MOG-specific splenocyte proliferation and IL-17 production and
      limited leukocyte infiltration into the spinal cord. Infection with T. crassiceps
      induced an anti-inflammatory cytokine microenvironment, including decreased TNF
      alpha production and high MOG-specific production of IL-4 and IL-10. While the
      mRNA expression of TNF-alpha and iNOS was lower in the brain of T. crassiceps
      infected mice with EAE, markers for AAMF were highly expressed. Furthermore, in
      these mice, there was reduced entry of CD3(+)Foxp3(-) cells into the brain. The
      T. crassiceps-induced immune regulation decreased EAE severity by dampening T
      cell activation, proliferation and migration to the CNS.

PMID- 21185557
TI  - Arsenic occurrence in drinking water supply systems in ten municipalities in
      Vojvodina Region, Serbia.
AB  - Vojvodina, a northern region of Serbia, belongs to the Pannonian Basin, whose
      aquifers contain high concentrations of arsenic. This study represents arsenic
      levels in drinking water in ten municipalities in Serbia. Around 63% of all water
      samples exceeded Serbian and European standards for arsenic in drinking water.
      Large variations in arsenic were observed among supply systems. Arsenic
      concentrations in public water supply systems in Vojvodina were much higher than
      in other countries in the Pannonian Basin.

PMID- 21185558
TI  - Determination of the appropriate catheter length for needle thoracostomy by using
      computed tomography scans of trauma patients in Japan.
AB  - BACKGROUND: Previous studies reported a high failure rate in relieving tension
      pneumothorax by needle thoracostomy, because the catheter was not sufficiently
      long to access the pleural space. The Advanced Trauma Life Support guideline
      recommends needle thoracostomy at the second intercostal space in the middle
      clavicular line using a 5.0-cm catheter, whereas the corresponding guideline in
      Japan does not mention a catheter length. It is necessary to measure the chest
      wall thickness (CWT) and determine the appropriate catheter length taking the
      differences of habitus in race and region into consideration. This study was
      designed to analyse CWT in Japanese trauma patients by computed tomography and to
      determine the percentage of patients whose pleural space would be accessible
      using a 5.0-cm catheter. PATIENTS AND METHODS: We performed a retrospective
      review of chest computed tomography of 256 adult Japanese trauma patients who
      were admitted to the level 1 trauma centre of Tokai University Hospital in
      Kanagawa, Japan between January and July 2008. In 256 patients, the CWT at 512
      sites (left and right sides) was measured by chest computed tomography at the
      second intercostal space in the middle clavicular line. The frequency of
      measurement sites <5.0 cm was calculated simultaneously. The samples were divided
      according to gender, side (left and right), abbreviated injury scale (<3, ?3),
      arm position during examination (up/down), and the existence or non-existence of
      associated injuries (pneumothorax, subcutaneous emphysema, and fracture of the
      sternum and ribs); the CWT of each group was compared. RESULTS: The mean CWT
      measured in 192 males and 64 females was 3.06+/-1.02 cm. The CWT values at 483
      sites (94.3%) were less than 5.0 cm. The CWT of females was significantly greater
      than that of males (3.66 cm vs. 2.85 cm, p<0.0001), and patients with
      subcutaneous emphysema had greater CWTs than those without it (4.16 cm vs. 3.01
      cm, p<0.0001). CONCLUSION: The mean CWT at the second intercostal space in the
      middle clavicular line was 3.06 cm. It is likely that over 94% of Japanese trauma
      patients could be treated with a 5.0-cm catheter.

PMID- 21185559
TI  - Effects of three approaches to standardized oral hygiene to reduce bacterial
      colonization and ventilator associated pneumonia in mechanically ventilated
      patients: a randomised control trial.
AB  - BACKGROUND: Ventilator associated pneumonia remains an important concern in the
      intensive care unit (ICU). An increasing body of evidence shows that mortality
      and morbidity can be reduced by implementing a range of preventive strategies,
      including optimizing oral hygiene. AIM: The aim of this feasibility study was to
      test two oral hygiene strategies on the effects of microbial colonization of
      dental plaque with respiratory pathogens (primary outcome) and incidence of
      ventilator associated pneumonia (secondary outcome). METHODS: A single blind
      randomised comparative study was conducted in a 20-bed adult intensive care unit
      in a university hospital. Patients with an expected duration of mechanical
      ventilation more than 48 h were eligible. Patients were randomised to one of
      three study regimens (Group A control, second hourly oral rinse with sterile
      water, Group B sodium bicarbonate mouth wash second hourly, and Group C twice
      daily irrigations with chlorhexidine 0.2% aqueous oral rinse and second hourly
      irrigations with sterile water). All study options included cleaning with a
      toothbrush and non foaming toothpaste. RESULTS: Data from a total of 109 patients
      were analyzed. Group A 43, Group B 33 and Group C 33 (mean age: 58 +/- 17 years,
      simplified acute physiology score II: 44 +/- 14 points). On admission no
      significant differences were found between groups for all clinical data. While
      Group B showed a greater trend to reduction in bacterial colonization no
      significant differences could be demonstrated at Day 4 of admission (p=0.302).
      The incidence of ventilator associated pneumonia was evenly spread between Groups
      B and C (5%) while Group A was only 1%. CONCLUSIONS: While a number of studies
      have advocated the use of various mouth rinses in reducing colonization of dental
      plaque a standardized oral hygiene protocol which includes the use of mechanical
      cleaning with a toothbrush may be a factor in the reduction of colonization of
      dental plaque with respiratory pathogens. This feasibility study provides data to
      inform future adequately powered studies.

PMID- 21185560
TI  - The quality and duration of sleep in the intensive care setting: an integrative
      review.
AB  - BACKGROUND: Sleep is essential for well-being and recovery from illness. The
      critically ill are in significant need of sleep but at increased risk of sleep
      loss and disruption. OBJECTIVES: To determine the quality and duration of sleep
      experienced by adults who are patients in intensive care units and factors
      affecting their sleep. DESIGN: An integrative approach was used for this
      literature review in order to explore the available evidence on this topic, which
      has yet to be fully investigated. DATA SOURCES: PubMed, CINAHL, Psychinfo, the
      Australian Digital Theses Program and ProQuest Dissertations and Theses
      (Interdisciplinary) databases were searched for studies conducted about sleep in
      adult intensive care units. Manual searches of papers identified from this search
      were performed to find additional studies. REVIEW METHODS: Data related to the
      quality and duration of sleep along with study design, sample size and intensive
      care context were extracted, evaluated and summarised. RESULTS: Total sleep time
      is normal or reduced with significant fragmentation. Light sleep is prolonged and
      deep and rapid eye movement sleep are reduced. The most likely factors affecting
      sleep quality are high sound levels, frequent interventions and medications. Data
      obtained from polysomnography are supported by patient self reports. Considerable
      variation in data exists between patients and studies affecting generalizability.
      Existing criteria for staging sleep may be inadequate for quantifying sleep in
      intensive care patients. CONCLUSIONS: There is evidence that intensive care
      patients' sleep is significantly disrupted. Alternative methods of quantifying
      sleep for intensive care patients may be required. Few large observational or
      interventional studies have used polysomnography and simultaneous recordings of
      intrinsic and extrinsic disruptive factors. These studies are required in order
      to improve sleep for intensive care patients.

PMID- 21185561
TI  - Effects of peroxisome proliferator activated receptor-gamma 2 gene Pro12Ala
      polymorphism on fasting blood lipids: a meta-analysis.
AB  - OBJECTIVE: Results from the published studies on the association of peroxisome
      proliferator activated receptor-gamma 2 (PPARgamma2) Pro12Ala polymorphism with
      blood lipids are conflicting. In this meta-analysis, we investigated the
      association of the Pro12Ala polymorphism with total cholesterol, triglycerides,
      low density lipoprotein cholesterol, and high-density lipoprotein cholesterol.
      METHODS: 74 studies with 52,998 subjects were included in this meta-analysis.
      Dominant model and additive model were used for this meta-analysis. RESULTS: We
      did not detect significant overall association of the Pro12Ala polymorphism with
      total cholesterol, low density lipoprotein cholesterol, or high-density
      lipoprotein cholesterol (P>0.05). Under dominant model, significant association
      between the PPARgamma2 Pro12Ala polymorphism and increased blood TC in male
      subjects was detected: standardized mean difference=0.10, 95% confidence interval
      (0.02, 0.22), P=0.02, Pheterogeneity=0.14. We found a marginal association of the
      Pro12Ala polymorphism with increased HDL-C in healthy subjects under dominant
      model: standardized mean difference=0.10, 95% confidence interval (-0.00, 0.20),
      P=0.06, Pheterogeneity=0.96. We also found subjects with genotype AlaAla have
      lower blood TG than subjects with genotype ProPro in Caucasians: for analysis
      including the outlier studies: SMD=-0.40, 95% CI (-0.76, -0.05), P=0.02,
      Pheterogeneity<0.00001, and for analysis excluding the outlier studies: SMD=
      0.23, 95% CI (-0.39, -0.06), P=0.006, Pheterogeneity=0.86. CONCLUSIONS: Our meta
      analysis suggests that, compared with non-carriers, carriers of Ala allele have
      significant increased blood TC in male subjects, and marginally significant
      increased blood HDL-C in healthy subjects. Our meta-analysis also supports that
      subjects with genotype AlaAla have lower blood TG than subjects with genotype
      ProPro in Caucasians.

PMID- 21185562
TI  - An approximate simulation model for initial luge track design.
AB  - Competitive and recreational sport on artificial ice tracks has grown in
      popularity. For track design one needs knowledge of the expected speed and
      acceleration of the luge on the ice track. The purpose of this study was to
      develop an approximate simulation model for luge in order to support the initial
      design of new ice tracks. Forces considered were weight, drag, friction, and
      surface reaction force. The trajectory of the luge on the ice track was estimated
      using a quasi-static force balance and a 1d equation of motion was solved along
      that trajectory. The drag area and the coefficient of friction for two runs were
      determined by parameter identification using split times of five sections of the
      Whistler Olympic ice track. The values obtained agreed with experimental data
      from ice friction and wind tunnel measurements. To validate the ability of the
      model to predict speed and accelerations normal to the track surface, a luge was
      equipped with an accelerometer to record the normal acceleration during the
      entire run. Simulated and measured normal accelerations agreed well. In a
      parameter study the vertical drop and the individual turn radii turned out to be
      the main variables that determine speed and acceleration. Thus the safety of a
      new ice track is mainly ensured in the planning phase, in which the use of a
      simulation model similar to this is essential.

PMID- 21185563
TI  - Rapid and sensitive drug metabolism studies by SU-8 microchip capillary
      electrophoresis-electrospray ionization mass spectrometry.
AB  - Monolithically integrated, polymer (SU-8) microchips comprising an
      electrophoretic separation unit, a sheath flow interface, and an electrospray
      ionization (ESI) emitter were developed to improve the speed and throughput of
      metabolism research. Validation of the microchip method was performed using
      bufuralol 1-hydroxylation via CYP450 enzymes as the model reaction. The
      metabolite, 1-hydroxybufuralol, was easily separated from the substrate
      (R(s)=0.5) with very good detection sensitivity (LOD=9.3nM), linearity (range: 50
      500nM, r(2)=0.9997), and repeatability (RSD(Area)=10.3%, RSD(Migrationtime)=2.5%
      at 80nM concentration without internal standard). The kinetic parameters of
      bufuralol 1-hydroxylation determined by the microchip capillary electrophoresis
      (CE)-ESI/mass spectrometry (MS) method, were comparable to the values presented
      in literature as well as to the values determined by in-house liquid
      chromatography (LC)-UV. In addition to enzyme kinetics, metabolic profiling was
      demonstrated using authentic urine samples from healthy volunteers after intake
      of either tramadol or paracetamol. As a result, six metabolites of tramadol and
      four metabolites of paracetamol, including both phase I oxidation products and
      phase II conjugation products, were detected and separated from each other within
      30-35s. Before analysis, the urine samples were pre-treated with on-chip, on-line
      liquid-phase microextraction (LPME) and the results were compared to those
      obtained from urine samples pre-treated with conventional C18 solid-phase
      extraction (SPE, off-chip cartridges). On the basis of our results, the SU-8 CE
      ESI/MS microchips incorporating on-chip sample pre-treatment, injection,
      separation, and ESI/MS detection were proven as efficient and versatile tools for
      drug metabolism research.

PMID- 21185564
TI  - Chromatographic behavior of xanthines in aqueous normal phase chromatography
      using titania stationary phase.
AB  - The chromatographic behavior of native titania was investigated in aqueous normal
      phase chromatography using a set of N-methylated xanthines as polar test solutes.
      In agreement with a hydrophilic interaction on a polar bed, the retention of
      xanthine models increased mainly along their molecular polarity. Adsorption of
      these molecules on the hydrated surface of titania prevailed as a retention
      mechanism for low water contents in the mobile phase. Several N-methylated
      xanthines could be easily discriminated along the number and position of their
      methyl groups while the nitrogen atom at position 3 was found deeply involved in
      the retention on titania. To get further insights on the interactions occurring
      on the surface of titania, the retention of xanthine derivatives based on ligand
      exchange was evaluated as a function of the buffer concentration and type. The
      separation efficiency of native titania for the set of N-methylated xanthines was
      comparable to that observed on zirconia but lower than that obtained on native
      silica due to mixed-mode interactions. However, titania exhibited a superior
      ability to recognize several isomeric positions of xanthine derivatives in
      comparison to zirconia and silica.

PMID- 21185565
TI  - Directly suspended droplet microextraction with in injection-port derivatization
      coupled to gas chromatography-mass spectrometry for the analysis of polyphenols
      in herbal infusions, fruits and functional foods.
AB  - A miniaturized liquid-phase extraction procedure based on directly suspended
      droplet microextraction is proposed for determining different classes of
      polyphenols. A derivatization reaction by means of in injection-port reaction
      with bis(trimethylsilyl)trifluoroacetamide is carried out to convert the polar
      non-volatile polyphenols into volatile derivatives. The separation and detection
      is carried out by coupling gas chromatography with mass spectrometry in the
      selected ion monitoring mode. The procedure uses undecanone, a low density
      organic solvent, and several factors influencing the extraction, collection
      efficiency and derivatization reaction are optimized. Excellent linearity was
      obtained for the range studied (0.05-500ngmL(-1)). The limits of detection are
      between 0.011 and 0.13ngmL(-1), depending on the compound, and the limits of
      quantification between 0.037 and 0.43ngmL(-1). The sensitivity and detection
      limits for polyphenols using the DSDME sample pretreatment method were very low.
      Enrichment factors are between 413 and 578. The recoveries obtained for spiked
      samples are satisfactory for all the compounds. The coupled miniaturized method
      is applied to the sensitive determination of both cis- and trans-resveratrol
      isomers, piceatannol, catechin, epicatechin, quercetin and fisetin in herbal
      infusions, fruits, juices and functional foods.

PMID- 21185566
TI  - TLC for pharmaceutical analysis in resource limited countries.
AB  - This review article discusses the sustainability and robust advantages of planar
      chromatography that are critical to the successful performance of product quality
      assessments in resource limited areas including field applications. Because of
      the robustness and ease of use, the training required for successful performance
      of the high performance thin layer chromatography (HPTLC) assessments is much
      lower than that of other technologies with comparable reproducibility such as
      high performance liquid chromatography (HPLC). Some of the successful
      applications of planar chromatography in resource limited countries are
      presented. It should be noted that these planar chromatographic technologies have
      much lower plate counts and therefore separation power than column technologies
      such as HPLC and gas liquid chromatography (GLC). However in finished
      pharmaceutical products there are generally few active ingredients which are
      assessed making the HPTLC adequate for these analyses. In addition at this time
      there is a much wider array of detection technologies available for HPLC and GLC.

PMID- 21185567
TI  - Continuous cell introduction and rapid dynamic lysis for high-throughput single
      cell analysis on microfludic chips with hydrodynamic focusing.
AB  - A chip-based microfluidic system for high-throughput single-cell analysis is
      described. The system was integrated with continuous introduction of individual
      cells, rapid dynamic lysis, capillary electrophoretic (CE) separation and laser
      induced fluorescence (LIF) detection. A cross microfluidic chip with one sheath
      flow channel located on each side of the sampling channel was designed. The
      labeled cells were hydrodynamically focused by sheath-flow streams and
      sequentially introduced into the cross section of the microchip under hydrostatic
      pressure generated by adjusting liquid levels in the reservoirs. Combined with
      the electric field applied on the separation channel, the aligned cells were
      driven into the separation channel and rapidly lysed within 33ms at the entry of
      the separation channel by Triton X-100 added in the sheath-flow solution. The
      maximum rate for introducing individual cells into the separation channel was
      about 150cells/min. The introduction of sheath-flow streams also significantly
      reduced the concentration of phosphate-buffered saline (PBS) injected into the
      separation channel along with single cells, thus reducing Joule heating during
      electrophoretic separation. The performance of this microfluidic system was
      evaluated by analysis of reduced glutathione (GSH) and reactive oxygen species
      (ROS) in single erythrocytes. A throughput of 38cells/min was obtained. The
      proposed method is simple and robust for high-throughput single-cell analysis,
      allowing for analysis of cell population with considerable size to generate
      results with statistical significance.

PMID- 21185569
TI  - A density functional approach to retention in chromatography with chemically
      bonded phases.
AB  - A density functional approach to the retention in a chromatography with
      chemically bonded phases is developed. The bonded phase is treated as brush built
      of grafted polymers. The chain molecules are modelled as freely jointed spheres.
      Segments of all components interact with the surface via the hard wall potential
      whereas interactions between the segments are described by Lennard-Jones (12-6)
      potential. The structure of the bonded phase is investigated. The distribution of
      different solutes in the stationary phases is determined. An influence of the
      following parameters on the retention is analyzed: the grafting density, the
      grafted chains length, the strength of molecular interactions, the solute sizes,
      temperature. The theoretical predictions are consisted with numerous experimental
      results.

PMID- 21185568
TI  - Enhanced comprehensive two-dimensional gas chromatographic resolution of
      polychlorinated biphenyls on a non-polar polysiloxane and an ionic liquid column
      series.
AB  - A total of 196 out of 209 polychlorobiphenyl (PCB) congeners were resolved using
      GC*GC-TOFMS with a non-polar/ionic liquid column series consisting of poly(50%-n
      octyl-50%-methyl)siloxane and (1,12-di(tripropylphosphonium)dodecane
      bis(trifluoromethansulfonyl)amide) in the first and second dimension,
      respectively. It has been found that 13 PCB congeners overlap in five doublets
      (CB12+CB13, CB62+CB75, CB70+CB76, CB97+CB125 and CB153+CB168) and one triplet
      (CB90+CB101+CB113). All toxic, "dioxin like" congeners were separated with no
      interferences from any PCB congener. The 109 PCBs present in Aroclor 1242 and the
      82 PCBs present in Aroclor 1260 were resolved GC*GC-TOFMS analysis on this column
      set.

PMID- 21185570
TI  - Application of a pH responsive multimodal hydrophobic interaction chromatography
      medium for the analysis of glycosylated proteins.
AB  - Protein glycosylation has significant effects on the structure and function of
      proteins. The efficient separation and enrichment of glycoproteins from complex
      biological samples is one key aspect and represents a major bottleneck of
      glycoproteome research. In this paper, we have explored pH multimodal hydrophobic
      interaction chromatography to separate glycosylated from non-glycosylated forms
      of proteins. Three different proteins, ribonuclease, invertase and IgG, have been
      examined and different glycoforms have been identified. The media itself shows
      strong responsiveness to small variations in pH, which makes it possible to fine
      tune the chromatographic conditions according to the properties of the protein
      isolated. Optimal glycoprotein separation has been obtained at pH 4. The pH
      responsive multimodal HIC medium in contrast to conventional HIC media is able to
      resolve contaminating DNA.

PMID- 21185571
TI  - Editorial on "Potential of nanoparticles in sample preparation" by R. Lucena,
      B.M. Simonet, S. Cardenas and M. Valcarcel.

PMID- 21185572
TI  - A prospective study on personality and the cortisol awakening response to predict
      posttraumatic stress symptoms in response to military deployment.
AB  - Few prospective studies on pre-trauma predictors for subsequent development of
      posttraumatic stress disorder (PTSD) have been conducted. In this study we
      prospectively investigated whether pre-deployment personality and the cortisol
      awakening response (CAR) predicted development of PTSD symptoms in response to
      military deployment. Furthermore, we hypothesized that potential effects of age,
      childhood trauma and previous deployment on development of PTSD symptoms were
      mediated via pre-deployment personality, CAR and PTSD symptoms. Path analysis was
      performed on data from 470 male soldiers collected before and six months after a
      4-month deployment to Afghanistan. Before deployment, personality was assessed
      with the short-form Temperament-Character Inventory and the Cook-Medley Hostility
      scale. In addition, pre-deployment saliva sampling for assessment of the CAR was
      performed immediately after awakening and 15, 30 and 60min thereafter. Pre
      deployment high hostility and low self-directedness represented intrinsic
      vulnerabilities for development of PTSD symptoms after deployment. The CAR
      assessed before deployment did not predict PTSD symptoms after deployment. Pre
      deployment low-to-moderate PTSD symptoms were associated with PTSD symptoms after
      deployment. As hypothesized, the effects of age and childhood trauma on PTSD
      symptoms after deployment were mediated via personality and pre-deployment PTSD
      symptoms. However, the number of previous deployments was not related to
      development of PTSD symptoms. The total model explained 24% of variance in PTSD
      symptoms after military deployment.

PMID- 21185573
TI  - Correlation between tumor-related seizures and molecular genetic profile in 103
      Chinese patients with low-grade gliomas: a preliminary study.
AB  - Tumor-related seizures are a well-known presenting symptom of primary brain
      tumors, particularly low-grade gliomas (LGGs). The objective of the present study
      was to investigate the possible correlation between tumor-related seizures and
      molecular genetic profile in Chinese patients with LGGs. A series of 103 LGGs,
      including 27 oligodendrogliomas, 41 oligoastrocytomas and 35 astrocytomas, was
      analyzed by denaturing high-performance liquid chromatography (DHPLC) for 1p and
      19q status, with particular emphasis on correlations with tumor-related seizures.
      Most oligodendrogliomas and oligoastrocytomas had LOH 1p and LOH 19q, which were
      rarely seen in combination in astrocytomas (p<0.001). LOH 1p and LOH 19q were
      also closely associated (p=0.022). The majority of patients with LGGs presented
      with seizures at disease onset (68.9% of all patients). The most common seizure
      type was secondary generalized seizures (81.7% of patients with seizures).
      Patients without LOH 19q were more likely to present with seizures (p=0.033),
      particularly secondary generalized seizures (p=0.005), than those with this
      alteration. The current study presented an update on studies on tumor-related
      seizures and molecular genetic profile, and brought forward putative candidate
      genes for secondary generalized seizures on chromosome 19q, based on the
      assumption that common molecular genetic pathways may exist for glioma
      development and tumor-related seizures.

PMID- 21185574
TI  - [The "athlete's heart": structure, function and differential diagnosis].
AB  - Long-term, intense sport activity induces morphologic and functional adaptations
      on cardiovascular system. The magnitude of these changes is determined by various
      factors, creating a specific condition: the "Athlete's Heart" (AH). It is
      important to distinguish this entity from other cardiomyopathies, taking into
      account that the differential diagnosis can be challenging. There has been an
      increase in the number of people practicing sports, which goes in parallel with
      the increase in the prevalence of AH. However, the proportion of asymptomatic
      subjects affected by cardiovascular diseases taking part on competitive sports,
      is also growing. We revise the main characteristics of AH, as well as the key
      points to distinguish AH from pathologic conditions. A delicate characterization
      as AH or cardiomyopathy would help to settle appropriate measures to lower the
      risk of sports-related sudden cardiac death.

PMID- 21185575
TI  - [Application of guidelines for secondary prevention of fracture and the FRAX
      index in patients with fragility fracture].
AB  - BACKGROUND AND OBJECTIVES: There are different guidelines for secondary
      prevention of fractures related with osteoporosis. Our aim is to analyse the
      appliance of such guidelines in a sample of patients with fragility fracture
      PATIENTS AND METHODS: Adult patients older than 50 years attended in the
      emergency department with a fragility fracture were invited to participate in a
      study for secondary prevention. Clinical data and densitometry for the FRAX index
      were recorded. Current guidelines were employed to calculate the number of
      patients who needed secondary prevention. RESULTS: With the appliance of current
      guidelines to 380 patients, 54-100% of women and 26-81% of men were candidates
      for treatment. For hip fractures the percentage was 81-100% and for forearm
      fractures 36-93%. FRAX index for hip fracture was >=3% in 35% of patients. The
      National Institute for Health and Clinical Excellence and the National
      Osteoporosis Foundation 2009 were the most restrictive guidelines (54% and 57%
      respectively). On the other hand the National Guideline Clearinghouse (87%) and
      the National Osteoporosis Guideline Group (93%). CONCLUSION: There are high
      differences in the percentage of patients who need treatment to prevent new
      fractures according to the guidelines. Fewer patients require treatment when the
      FRAX index is included in a guideline.

PMID- 21185576
TI  - Association between extended-release niacin treatment and glycemic control in
      patients with type 2 diabetes mellitus: analysis of an administrative-claims
      database.
AB  - The aim of the study was to evaluate trends in antihyperglycemic agents (AHAs)
      use in patients with type 2 diabetes mellitus (T2DM) newly initiating extended
      release niacin (ERN) compared with other lipid-modifying therapy (LMT). United
      States administrative-claims data identified adults with T2DM on AHAs who
      received a new prescription for ERN or another LMT between January 2001 and June
      2003 (index date), and these adults were followed for 12 months. Inclusion
      criteria were (1) stable T2DM as defined by International Classification of
      Diseases, Ninth Revision, codes and also receiving at least 2 AHA prescriptions
      12 to 24 months before initiating ERN or LMT treatment and (2) at least 2
      prescriptions within 12 months before the onset of ERN or LMT. Trends in AHA
      prescriptions 12 months before (baseline) and after (follow-up) index date were
      defined as (1) no change (ie, stable T2DM), (2) increased (ie, worsening T2DM),
      or (3) reduced (ie, improved T2DM). Among 3799 patients with T2DM, 392 (10.3%)
      were treated with ERN and 3407 (89.7%) were treated with other LMT. In the ERN
      cohort, 82.1% of patients experienced no change in AHA prescriptions between
      baseline and follow-up compared with 79.4% of patients in the LMT cohort (P =
      .20); 13% of the ERN cohort and 16% of the LMT cohort (P = .17) experienced a
      dose increase or the addition of another AHA; and 5% of both cohorts were
      prescribed fewer AHAs or switched to a lower dose (P = .92). Treatment with ERN
      (vs other types of LMT) did not significantly increase AHA use, implying that
      T2DM status did not worsen in this cohort.

PMID- 21185577
TI  - Relationship between splenic sequestration and thrombocytopenia in Trypanosoma
      evansi infection in rats.
AB  - Trypanosoma evansi infections in domestic animals are characterized by anemia and
      thrombocytopenia. The cause of the platelets decrease is unknown, but researchers
      suggest that thrombocytopenia may result from damage of the bone marrow, reduced
      survival of platelets, auto-immune thrombocytopenia, disseminated intravascular
      coagulation and splenic sequestration. Some of these causes have already been
      tested by our research group and found to be unrelated. Therefore, this study has
      the objective of testing the hypothesis that splenic sequestration might be
      responsible for thrombocytopenia in T. evansi-infected rats. A total of 28 rats
      assigned to four groups were used in the experiment. Group A rats were
      splenectomized and infected with T. evansi, group B rats were infected with T.
      evansi, group C rats were splenectomized, but not infected and group D rats were
      normal controls. Five days post-infection all rats were anesthetized and blood
      was collected in order to measure the number of circulating platelets, fibrinogen
      levels, prothrombin time (PT) and activated partial thromboplastin time (aPTT).
      The spleens of groups B and D were weighed at necropsy. The infected animals
      (groups A and B) showed a significant reduction in platelets and increased PT and
      aPTT when compared to negative control groups (groups C and D). Animals from
      group A showed increased levels of fibrinogen. The mean weight of spleen differed
      between group B (2.62g) and group D (0.55g). It was concluded that there is no
      relationship between thrombocytopenia and splenic sequestration in infection by
      T. evansi.

PMID- 21185578
TI  - [14th Workshop on peripheral nervous system diseases. Forward].

PMID- 21185579
TI  - [An unrecognized cause of myelopathy associated with copper deficiency: the use
      of denture cream].
AB  - We report two patients with myelopathy associated with copper deficiency and
      pancytopenia. Excessive intake of zinc can lead to a severe deficiency of copper
      reducing the absorption of ingested copper. The patients had in common
      consumption of denture adhesive paste containing zinc. In both patients,
      laboratory tests showed a combination of copper deficiency, hyperzincemia and
      increased urinary zinc level. The use of a denture cream was stopped. Copper
      supplementation, initially subcutaneously then oral corrected the copper
      deficiency and pancytopenia. Clinically, the pain faded but the gait disturbance
      persisted. Copper deficiency associated with the use of denture cream rich in
      zinc is an unrecognized cause of myelopathy associated with pancytopenia which
      should be diagnosed early to establish appropriate therapeutic measures to
      minimize neurological complications.

PMID- 21185580
TI  - Satureja khozestanica essential oil ameliorates progression of diabetic
      nephropathy in uninephrectomized diabetic rats.
AB  - Diabetic nephropathy is the common cause of leading to end stage of renal disease
      (ESRD). Satureja khozestanica essential oil (SKEO) was used as an antioxidant and
      antidiabetic for the inhibition of diabetic nephropathy. Forty male rats were
      uninephrectomized and divided in four groups randomly; group one as control,
      group two diabetic untreatment, groups three and four treatment with SKEO by 250
      or 500 ppm in drinking water, respectively. Diabetes was induced in the second,
      third and fourth groups by alloxan injection subcutaneously. After eight weeks
      treatment, serum malondialdehyde, serum creatinine and serum urea were measured.
      The kidney paraffin sections were stained by periodic acid Schiff method.
      Glomerular volume and glomerular number were estimated by stereological rules.
      Glomerular sclerosis was studied semi-quantitatively. The means were compared by
      SPSS 13 software and Mann-Whitney test at p<0.05. Satureja khozestanica essential
      oil (250 or 500 ppm) significantly inhibited the progression of glomerular
      hypertrophy, glomerular number loss, glomerulosclerosis, lipid peroxidation,
      serum urea and creatinine compared with the diabetic untreated group. The level
      of glomerular number, serum malondialdehyde, serum creatinine and urea in the
      treated groups was significantly maintained at the same level as that of the
      control group. In conclusion, satureja essential oil significantly can ameliorate
      glomerular hypertrophy, loss of glomerular number, glomerulosclerosis and
      attenuated serum urea and serum creatinine in diabetic rats.

PMID- 21185581
TI  - Podoplanin is expressed by a sub-population of human foetal rib and knee joint
      rudiment chondrocytes.
AB  - The aim of this study was to determine if podoplanin was expressed by rudiment
      chondrocytes in human foetal cartilages. Podoplanin was immunolocalised in first
      trimester human foetal rib and knee joint rudiments to a sub-population of
      chondrocytes deep in the rib rudiments, tibial and femoral growth plates and
      cells associated with the cartilage canals of the foetal knee joint rudiments.
      Lymphatic vessels in the loose stromal tissues surrounding the developing
      rudiments were also demonstrated on the same histology slides using
      antipodoplanin (MAb D2-40) and anti-LYVE-1 and differentiated from CD-31 positive
      blood vessels confirming the discriminative capability of the antibody
      preparations used. The D2-40 positive rib and knee rudiment chondrocytes were not
      stained with antibodies to LYVE-1, CD-31 or CD-34 however perlecan was a
      prominent pericellular proteoglycan around these cells confirming their
      chondrogenic phenotype. Discernable differences were evident between the surface
      and deep rudiment chondrocytes in terms of their antigen reactivities detected
      with MAb D2-40 or antiperlecan antibodies. Binding of the cytoplasmic tail of
      PDPN to the ERM proteins ezrin, radixin and moeisin may result in changes in
      cytoskeletal organisation which alter the phenotype of this central population of
      rudiment cells. This may contribute to morphological changes in the rudiment
      cartilages which lead to establishment of the primary ossification centres and is
      consistent with their roles as transient developmental scaffolds during tissue
      development.

PMID- 21185582
TI  - Thermal behavior of acousto-optic devices: effects of ultrasound absorption and
      transducer losses.
AB  - In the present paper we analyze the electric and acoustic losses in acousto-optic
      devices, especially in their ultrasonic transducers and the related thermal
      effects. We include electric and acoustic losses into the classical electric
      equivalent model of the transducer, to explain the characteristics of the
      measured electric and thermal behavior. Measured temperature distributions on the
      acousto-optic crystal faces serve visualization of the conversion efficiency of
      the radio-frequency input to bulk acoustic waves. We show that the pronounced
      acoustic frequency dependence of the temperature distribution is in correlation
      with the frequency dependent losses in the transducer and in the bulk. We also
      demonstrate experimentally the effectiveness of our active and passive heat
      removing and temperature stabilization methods.

PMID- 21185583
TI  - Oxidative removal of bisphenol A using zero valent aluminum-acid system.
AB  - Bisphenol A (BPA), a controversial endocrine disruptor, is ubiquitous in the
      aquatic environment. In this study, the oxidative degradation of BPA and its
      mechanism using zero valent aluminum (ZVAl)-acid system under air-equilibrated
      conditions was investigated. Under pH <3.5 acidic conditions, ZVAl demonstrated
      an excellent capacity to remove BPA. More than 75% of BPA was eliminated within
      12 h in pH 1.5 reaction solutions initially containing 4.0 g/L aluminum and 2.0
      mg/L BPA at 25 +/- 1  degrees C. The removal of BPA was further accelerated with
      increasing aluminum loadings. Higher temperature and lower initial pH also
      facilitated BPA removal. The addition of Fe(2+) into the ZVAl-acid system
      significantly accelerated the reaction likely due to the enhancing transformation
      of H(2)O(2) to HO via Fenton reaction. Furthermore, the primary products or
      intermediates including monohydroxylated BPA, hydroquinone, 2-(4
      hydroxyphenyl)propane and 4-isopropenylphenol, were identified and a possible
      reaction scheme was proposed. The remarkable capacity of the ZVAl-acid system in
      removing BPA displays its potential application in the treatment of organic
      compound-contaminated water.

PMID- 21185584
TI  - The interaction of boron with goethite: experiments and CD-MUSIC modeling.
AB  - Boron (B) is an essential element for plants and animals growth that interacts
      with mineral surfaces regulating its bioavailability and mobility in soils,
      sediments, and natural ecosystems. The interaction with mineral surfaces is quite
      important because of a narrow range between boron deficiency and toxicity limits.
      In this study, the interaction of boric acid with goethite (alpha-FeOOH) was
      measured in NaNO(3) background solution as a function of pH, ionic strength,
      goethite and boron concentration representing as adsorption edges and isotherms.
      Boron adsorption edges showed a bell-shaped pattern with maximum adsorption
      around pH 8.50, whereas adsorption isotherms were rather linear. The adsorption
      data were successfully described with the CD-MUSIC model in combination with the
      Extended Stern (ES) model. The charge distribution (CD) of inner-sphere boron
      surface complexes was calculated from the geometry optimized with molecular
      orbital calculations applying density functional theory (MO/DFT). The CD modeling
      suggested dominant binding of boric acid as a trigonal inner-sphere complex with
      minor contributions of a tetrahedral inner-sphere complex (at high pH) and a
      trigonal outer-sphere complex (at low pH). The interpretation with the CD model
      is consistent with the spectroscopic observations.

PMID- 21185585
TI  - Morphometric variables can be analyzed using cladistic methods: a reply to Adams
      et al.

PMID- 21185586
TI  - Point-source effects on N and P uptake in a forested and an agricultural
      Mediterranean streams.
AB  - We examined the effect of point-source inputs from wastewater treatment plants
      (WWTP) on in-stream uptake of ammonium, nitrate and phosphate and compared it
      between two streams draining catchments with contrasting land use. The selected
      streams were La Tordera and Gurri (NE Spain), draining a forest- and an
      agriculture-dominated catchment, respectively. In each stream, we compared
      nutrient uptake metrics, estimated from nutrient additions, between two reaches
      located upstream and downstream of a WWTP input. Measurements were done on 8-9
      dates during 2002-2003. In La Tordera, the point-source increased concentrations
      of all studied nutrients; whereas in Gurri, this effect was less evident. Point
      source effects on nutrient uptake differed between the two streams, and among
      solutes. In La Tordera, uptake lengths (S(w)) of ammonium and phosphate averaged
      hundreds of meters above the point-source, and increased (i.e., decreased uptake
      efficiency) 4 and 5 times, respectively, below the point-source. S(w) of nitrate
      was >=2km regardless of reach location. In Gurri, S(w) of all studied nutrients
      was within the km range in the two reaches. In this stream, diffuse nutrient
      inputs from adjacent fields may overwhelm the local effect of the point-source
      input. Uptake velocities (v(f)) of the studied nutrients ranged between 10EXP(-6)
      and 10EXP(-4)m/s in the two streams, and were similar between the two reaches in
      each stream. However, phosphate v(f) decreased under increasing concentrations
      following a power function. This trend remained significant when combining our
      results with those compiled from literature, suggesting the efficiency loss
      response may be a general trend for phosphate across streams. The relative
      increases in uptake rates (U) below the point-source were proportional to the
      relative point-source contribution to downstream nutrient loads, especially for
      ammonium and nitrate. However, the increases in U were not enough to compensate
      for the increases in nutrient loads downstream of the WWTP input.

PMID- 21185587
TI  - Leukocytosis may be seen in patients with undiagnosed myelopoliferative
      disorders, factitious leukocytosis and venous thromboembolism.

PMID- 21185588
TI  - Mini-incision vasectomy reversal using no-scalpel vasectomy principles: efficacy
      and postoperative pain compared with traditional approaches to vasectomy
      reversal.
AB  - OBJECTIVES: To evaluate the efficacy and postoperative morbidity of a mini
      incision vasectomy reversal (MIVR) using no-scalpel vasectomy principles compared
      with traditional incisional approaches to vasectomy reversal (VR). METHODS: Of
      164 patients undergoing consecutive VR, 139 underwent bilateral vasovasostomy
      (55% bilateral MIVR, 24% mixed MIVR/traditional incision VR, and 21% bilateral
      traditional incision VR). The MIVRs were performed using a subcentimeter incision
      after the vas deferens was captured and delivered through the skin using the no
      scalpel vasectomy principles and instruments. Semen analyses were obtained at 3
      month intervals postoperatively until pregnancy was achieved. Motile sperm in the
      ejaculate after VR defined patency. Pain and functional recovery after surgery
      were evaluated using a previously validated 10-point pain scale adapted to VR.
      The no-scalpel vasectomy patients served as controls for the postoperative pain
      assessments. RESULTS: The median follow-up was 11.6 months. The patency rate was
      96%, 100%, and 91% for the MIVR, mixed MIVR/traditional incision, and bilateral
      traditional incision VR, respectively (P = .4). The semen parameters did not
      significantly differ among the VR approaches. The pain severity during the first
      48 hours after surgery was significantly less (P < .05) for the patients who had
      undergone bilateral MIVR than for the patients who had undergone traditional
      incision VR and did not significantly differ from that of the men who had
      undergone no-scalpel vasectomy. The patients returned to normal activities an
      average of 2 days earlier after MIVR than after traditional incision VR.
      CONCLUSIONS: The results of our study have shown that MIVR does not compromise
      patency outcomes or semen parameters compared with more traditional approaches to
      VR and results in less pain during the early period of recovery after surgery and
      quicker functional recovery.

PMID- 21185589
TI  - Use of tandem double J stents in the management of recurrent and recalcitrant
      ureteral stenosis after kidney transplantation.
AB  - OBJECTIVE: To evaluate the use of tandem double J stents in recalcitrant ureteral
      stenosis after kidney transplant. METHODS: We reviewed patients who underwent
      tandem double J stent placement after kidney transplant, assessing demographics
      (gender, age, cause of renal failure, recipient implantation site, blood
      pressure, donor status), renal function, biopsy results, site of stenosis,
      dilations, time with tandem stents, and outcome. Success was defined as ureteral
      patency without reconstructive surgery. Student t test was used for creatinine
      levels. Multivariate survival analysis identified risk factors for failure.
      RESULTS: A total of 19 patients (mean age 36.6 years) were included. The most
      common site of ureteral stenosis was distal (79%). Average number of biopsies
      before tandem stents was 1.8 (0-5) and, pathology results showed acute rejection
      in 16%. Percutaneous nephrostomy was performed after 66.8 +/- 140.8 weeks from
      transplantation date. Dilations averaged 2 +/- 1.1 (0-4) before tandem placement.
      Renal function improved after tandem stents (P < .01) and remained stable
      throughout follow-up (P = .147). The patency success rate was 58% with a mean of
      48.7 +/- 48 weeks with tandem in place. The failure rate was 26%, with a mean of
      16 +/- 7 weeks for tandem time. No perioperative complications were identified.
      Number of dilations before tandem was the only factor associated with failure
      (hazard ratio = 2.61; confidence interval = 1.150-5.908, P < .03). Proximal
      strictures (P = .072) and renal function (P = .067) were associated with a trend
      for tandem stent failure. CONCLUSIONS: Tandem stents can treat recurrent and
      recalcitrant ureteral stenosis after kidney transplantation that failed previous
      balloon dilation or ureteral reconstruction.

PMID- 21185590
TI  - Onlay on albuginea: modified onlay preputial island flap urethroplasty for single
      stage repair of primary severe hypospadias requiring urethral plate division.
AB  - OBJECTIVES: To describe a modified onlay preputial island flap (OIF)
      urethroplasty to also be used in patients requiring urethral plate transection
      for penile straightening. METHODS: A total of 14 cases with primary severe
      hypospadias underwent the modified OIF urethroplasty as follows. After skin
      degloving, the corpora cavernosa were dissected ventrally. The urethral plate was
      mobilized and, if curvature >30 degrees  persisted, transected just proximally to
      the coronal sulcus. A pedicled preputial island flap was elevated and placed as
      an onlay to create the neourethra. It was sewn to the margins of the urethral
      plate proximally and distally. In contrast, in the portion of the shaft without a
      plate, it was sewn directly to the albuginea of the corpora cavernosa with 2
      parallel suture lines. Glanuloplasty and skin closure followed as in standard
      onlay repairs. RESULTS: After a median follow-up of 7 months (range 5 to 27), 3
      patients (21%) developed complications requiring additional surgery (1 simple
      fistula, 1 partial urethroplasty breakdown, and 1 ballooning of the neourethra).
      None of the remaining patients presented with residual curvature or voiding
      problems, according to the parental report. CONCLUSIONS: The results of the
      present preliminary experience suggest that OIF urethroplasty can also be
      performed in cases requiring urethral plate transection. It can be accomplished
      by suturing the preputial flap directly to the albuginea of the corpora
      cavernosa. Although we acknowledge that a larger number of cases and longer
      follow-up are necessary, we believe this technique should be incorporated into
      the armamentarium of hypospadiologists.

PMID- 21185592
TI  - The PIERS trial: hope for averting deaths from pre-eclampsia.

PMID- 21185591
TI  - Prediction of adverse maternal outcomes in pre-eclampsia: development and
      validation of the fullPIERS model.
AB  - BACKGROUND: Pre-eclampsia is a leading cause of maternal deaths. These deaths
      mainly result from eclampsia, uncontrolled hypertension, or systemic
      inflammation. We developed and validated the fullPIERS model with the aim of
      identifying the risk of fatal or life-threatening complications in women with pre
      eclampsia within 48 h of hospital admission for the disorder. METHODS: We
      developed and internally validated the fullPIERS model in a prospective,
      multicentre study in women who were admitted to tertiary obstetric centres with
      pre-eclampsia or who developed pre-eclampsia after admission. The outcome of
      interest was maternal mortality or other serious complications of pre-eclampsia.
      Routinely reported and informative variables were included in a stepwise backward
      elimination regression model to predict the adverse maternal outcome. We assessed
      performance using the area under the curve (AUC) of the receiver operating
      characteristic (ROC). Standard bootstrapping techniques were used to assess
      potential overfitting. FINDINGS: 261 of 2023 women with pre-eclampsia had adverse
      outcomes at any time after hospital admission (106 [5%] within 48 h of
      admission). Predictors of adverse maternal outcome included gestational age,
      chest pain or dyspnoea, oxygen saturation, platelet count, and creatinine and
      aspartate transaminase concentrations. The fullPIERS model predicted adverse
      maternal outcomes within 48 h of study eligibility (AUC ROC 0.88, 95% CI 0.84
      0.92). There was no significant overfitting. fullPIERS performed well (AUC ROC
      >0.7) up to 7 days after eligibility. INTERPRETATION: The fullPIERS model
      identifies women at increased risk of adverse outcomes up to 7 days before
      complications arise and can thereby modify direct patient care (eg, timing of
      delivery, place of care), improve the design of clinical trials, and inform
      biomedical investigations related to pre-eclampsia. FUNDING: Canadian Institutes
      of Health Research; UNDP/UNFPA/WHO/World Bank Special Programme of Research,
      Development, and Research Training in Human Reproduction; Preeclampsia
      Foundation; International Federation of Obstetricians and Gynecologists; Michael
      Smith Foundation for Health Research; and Child and Family Research Institute.

PMID- 21185593
TI  - Role of material-driven fibronectin fibrillogenesis in cell differentiation.
AB  - Fibronectin (FN) is a ubiquitous extracellular matrix protein (ECM) protein that
      is organized into fibrillar networks by cells through an integrin-mediated
      process that involves contractile forces. This assembly allows for the unfolding
      of the FN molecule, exposing cryptic domains that are not available in the native
      globular FN structure and activating intracellular signalling complexes. However,
      organization of FN into a physiological fibrillar network upon adsorption on a
      material surface has not been observed. Here we demonstrate cell-free, material
      induced FN fibrillogenesis into a biological matrix with enhanced cellular
      activities. We found that simple FN adsorption onto poly(ethyl acrylate)
      surfaces, but not control polymers, triggered FN organization into a fibrillar
      network via interactions in the amino-terminal 70 kDa fragment, which is involved
      in the formation of cell-mediated FN fibrils. Moreover, the material-driven FN
      fibrils exhibited enhanced biological activities in terms of myogenic
      differentiation compared to individual FN molecules and even type I collagen. Our
      results demonstrate that molecular assembly of FN can take place at the material
      interface, giving rise to a physiological protein network similar to fibrillar
      matrices assembled by cells. This research identifies material surfaces that
      trigger the organization of extracellular matrix proteins into biological active
      fibrils and establishes a new paradigm to engineer ECM-mimetic biomaterials.

PMID- 21185594
TI  - Cytotoxicity of, and innate immune response to, size-controlled polypyrrole
      nanoparticles in mammalian cells.
AB  - Monodisperse polypyrrole (PPy) nanoparticles with five different diameters (20,
      40, 60, 80, and 100 nm) were fabricated via chemical oxidation polymerization in
      order to evaluate size-dependent cytotoxicity. The cellular uptake of PPy
      nanoparticles in human lung fibroblasts (IMR90) and mouse alveolar macrophages
      (J774A.1) was observed by transmission electron microscopy. The nanoparticles
      were internalized into the IMR90 via endocytosis. In the J774A.1, the
      nanoparticles were entered via phagocytosis and endocytosis. Endocytosed
      nanoparticles were transported to lysosome via endosome-network. The cytotoxicity
      and innate immune response of PPy-treated cells were systematically investigated
      by viability assay, oxidative stress, apoptosis/necrosis, and expression of
      costimulatory molecules. The viability, oxidative stress, and apoptosis/necrosis
      of PPy-treated cells revealed size- and dose-dependency. Because of phagocytosis,
      PPy treatment had more adverse effects on the J774A.1 than the IMR90. Innate
      immune response of PPy-treated macrophages was measured by the expression of
      costimulatory molecules on surface of the cells. The expression of costimulatory
      molecules involved in Th1 response (CD40 and CD80) was lightly up-regulated and
      the other costimulatory molecule related in Th2 response (CD86) was less
      expressed than a negative control. These findings may provide better
      nanotoxicological information of polymer nanomaterials, and support the further
      development of PPy nanoparticles in bioelectronic applications.

PMID- 21185595
TI  - Tumor transfection after systemic injection of DNA lipid nanocapsules.
AB  - With the goal of generating an efficient vector for systemic gene delivery, a new
      kind of nanocarrier consisting of lipid nanocapsules encapsulating DOTAP/DOPE
      lipoplexes (DNA LNCs) was pegylated by the post-insertion of amphiphilic and
      flexible polymers. The aim of this surface modification was to create a long
      circulating vector, able to circulate in the blood stream and efficient in
      transfecting tumoral cells after passive targeting by enhanced permeability and
      retention effect (EPR effect). PEG conformation, electrostatic features, and
      hydrophylicity are known to be important factors able to influence the
      pharmacokinetic behaviour of vectors. In this context, the surface structure
      characteristics of the newly pegylated DNA LNCs were studied by measuring
      electrophoretic mobility as a function of ionic strength in order to establish a
      correlation between surface properties and in vivo performance of the vector.
      Finally, thanks to this PEGylation, gene expression was measured up to 84-fold
      higher in tumor compared to other tested organs after intravenous injection. The
      present results indicate that PEGylated DNA LNCs are promising carriers for an
      efficient cancer gene therapy.

PMID- 21185596
TI  - Chimeric fibronectin matrix mimetic as a functional growth- and migration
      promoting adhesive substrate.
AB  - Therapeutic protein engineering combines genetic, biochemical, and functional
      information to improve existing proteins or invent new protein technologies.
      Using these principles, we developed an approach to deliver extracellular matrix
      (ECM) fibronectin-specific signals to cells. Fibronectin matrix assembly is a
      cell-dependent process that converts the inactive, soluble form of fibronectin
      into biologically-active ECM fibrils. ECM fibronectin stimulates cell functions
      required for normal tissue regeneration, including cell growth, spreading,
      migration, and collagen reorganization. We have developed recombinant fibronectin
      fragments that mimic the effects of ECM fibronectin on cell function by coupling
      the cryptic heparin-binding fragment of fibronectin's first type III repeat
      (FNIII1H) to the integrin-binding domain (FNIII8-10). GST/III1H,8-10 supports
      cell adhesion and spreading and stimulates cell proliferation to a greater extent
      than plasma fibronectin. Deletion and site-specific mutant constructs were
      generated to identify the active regions in GST/III1H,8-10 and reduce construct
      size. A chimeric construct in which the integrin-binding, RGDS loop was inserted
      into the analogous site in FNIII8 (GST/III1H,8(RGD)), supported cell adhesion and
      migration, and enhanced cell proliferation and collagen gel contraction.
      GST/III1H,8(RGD) was expressed in bacteria and purified from soluble lysate
      fractions by affinity chromatography. Fibronectin matrix assembly is normally up
      regulated in response to tissue injury. Decreased levels of ECM fibronectin are
      associated with non-healing wounds. Engineering fibronectin matrix mimetics that
      bypass the need for cell-dependent fibronectin matrix assembly in chronic wounds
      is a novel approach to stimulating cellular activities critical for tissue
      repair.

PMID- 21185597
TI  - Tissue response to poly(L-lactic acid)-based blend with phospholipid polymer for
      biodegradable cardiovascular stents.
AB  - A temporary cardiovascular stent device by bioabsorbable materials might reduce
      late stent thrombosis. A water-soluble amphiphilic phospholipid polymer bearing
      phosphorylcholine groups (PMB30W) was blended with a high-molecular-weight poly(l
      lactic acid) (PLLA) to reduce unfavorable tissue responses at the surface. The
      PLLA implants and the polymer blend (PLLA/PMB30W) implants were inserted into
      subcutaneous tissues of rats, the infrarenal aorta of rats, and the internal
      carotid arteries of rabbits. After 6 months subcutaneous implantation, the
      PLLA/PMB30W maintained high density of phosphorylcholine groups on the surface
      without a significant bioabsorption. After intravascular implantation, the cross
      sectional areas of polymer tubing with diameters less than 1.6 mm were
      histomorphometrically measured. Compared to the PLLA tubing, the PLLA/PMB30W
      tubing significantly reduced the thrombus formation during 30 d of implantation.
      Human peripheral blood mononuclear cells were cultured on the PLLA and the
      PLLA/PMB30W to compare inflammatory reactions. Enzyme-linked immunosorbent assay
      quantified substantially decreased proinflammatory cytokines in the case of the
      PLLA/PMB30W. They were almost the same level as the negative controls. Thus, we
      conclude that the phosphorylcholine groups could reduce tissue responses
      significantly both in vivo and in vitro, and the PLLA/PMB30W is a promising
      material for preparing temporary cardiovascular stent devices.

PMID- 21185598
TI  - Persistent babesiosis in a stem cell transplant recipient.

PMID- 21185599
TI  - Splenic infarction associated with rapidly progressive chronic lymphocytic
      leukemia with complex karyotype and ATM mutation.

PMID- 21185600
TI  - Correlation between genetic polymorphisms of the hOCT1 and MDR1 genes and the
      response to imatinib in patients newly diagnosed with chronic-phase chronic
      myeloid leukemia.
AB  - The association between seven polymorphisms in the genes hOCT1 and MDR1, encoding
      for imatinib transporter proteins, and the response to imatinib 400mg/daily was
      investigated in 65 patients newly diagnosed with chronic-phase chronic myeloid
      leukemia. The AA genotype at the rs6935207 hOCT1 polymorphic locus was not
      detected in patients with inadequate response to imatinib. The CC genotype at the
      rs1045642 (C3435T) MDR1 locus was associated with primary failure, whereas a T
      allele at the rs2032582 (G2677T/A) MDR1 locus seemed to protect from primary
      failure. Beside, the MDR1 haplotype 1236T-2677G-3435C was more frequently found
      in patients primarily resistant to imatinib.

PMID- 21185602
TI  - Short-term consultancy and collaborative evaluation in a post-conflict and
      humanitarian setting: lessons from Afghanistan.
AB  - In humanitarian and post-conflict settings, evaluations are rarely participative
      due to constraints such as limited time, resources or expertise. External
      evaluators control most of the process while stakeholders are the most consulted
      but are rarely participants. Yet, we believe that not all evaluators are
      comfortable with that sort of practice and that it is possible to involve
      stakeholders in the evaluation process in the field. The objective of this paper
      is to demonstrate, that even in a post-conflict setting such as Afghanistan in
      2003, a short term consultancy allowed for the adoption of a collaborative and
      useful evaluation approach. After the description of the whole process in order
      to facilitate its reproduction by humanitarian evaluators, we discuss strengths
      and weaknesses of the process and highlight some positives and negatives factors
      affecting the use of evaluation finding.

PMID- 21185601
TI  - Genetic, enzymatic and developmental alterations observed in Caiman latirostris
      exposed in ovo to pesticide formulations and mixtures in an experiment simulating
      environmental exposure.
AB  - In South America, economic interests in last years have produced a constant
      increase in transgenic soybean cropping, with the corresponding rise in pesticide
      formulated products. The aim of this study was to determine the effects of
      pesticides formulations and mixtures on a South American caiman, Caiman
      latirostris, after in ovo exposure. We conducted a field-like experiment which
      simulates the environmental exposure that a caiman nest can receive in
      neighbouring croplands habitats. Experimental groups were Control group,
      Treatment 1: sprayed with a glyphosate herbicide formulation, and Treatment 2:
      sprayed with a pesticide mixture of glyphosate, endosulfan and cypermethrin
      formulations. Results demonstrated genotoxicity, enzymatic and metabolic
      alterations, as well as growth delay in caimans exposed in ovo to Treatments 1
      and 2, showing a higher toxicity for the mixture. Integral evaluation through
      biomarkers of different biological meaning is highly informative as early
      indicators of contamination with pesticides and mixtures in this wildlife
      species.

PMID- 21185603
TI  - Genetic characteristics of eighty-seven patients with the Wiskott-Aldrich
      syndrome.
AB  - The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive immune deficiency
      disorder characterized by thrombocytopenia, small platelet size, eczema,
      recurrent infections, and increased risk of autoimmune disorders and
      malignancies. WAS is caused by mutations in the WASP gene which encodes WASP, a
      502-amino acid protein. WASP plays a critical role in actin cytoskeleton
      organization and signalling, and functions of immune cells. We present here the
      results of genetic analysis of patients with WAS from eleven Eastern and Central
      European (ECE) countries and Turkey. Clinical and haematological information of
      87 affected males and 48 carrier females from 77 WAS families were collected. The
      WASP gene was sequenced from genomic DNA of patients with WAS, as well as their
      family members to identify carriers. In this large cohort, we identified 62
      unique mutations including 17 novel sequence variants. The mutations were
      scattered throughout the WASP gene and included single base pair changes (17
      missense and 11 nonsense mutations), 7 small insertions, 18 deletions, and 9
      splice site defects. Genetic counselling and prenatal diagnosis were applied in
      four affected families. This study was part of the J Project aimed at identifying
      genetic basis of primary immunodeficiency disease in ECE countries. This report
      provides the first comprehensive overview of the molecular genetic and
      demographic features of WAS in ECE.

PMID- 21185604
TI  - Dyadic and triadic skills in preterm and full term infants: a longitudinal study
      in the first year.
AB  - This longitudinal study examined dyadic and triadic skills in 26 preterm and 31
      full term infants at 3, 6 and 9 months of age. In dyadic interaction, infants
      engaged with a stranger in face-to-face play interrupted by a still-face episode.
      In triadic interaction, infants interacted with the adult stranger as she
      coordinated gaze between the infant and object. Both groups were sensitive for
      non-contingency in both dyadic and triadic interactions. There were significant
      group and developmental differences for dyadic and triadic competencies. Compared
      to full term infants, preterms made less positive elicits during the still-face
      at 6 months and followed gaze less at 9 months of age. Six-month dyadic skills
      and 9-month triadic competencies were positively related in preterm and full term
      infants.

PMID- 21185605
TI  - BINS validation - Bayley neurodevelopmental screener in Brazilian preterm
      children under risk conditions.
AB  - Psychometric researches increase in Brazil. Bayley Infant Neurodevelopment
      Screener - BINS (Aylward, 1995) is a low cost, fast instrument. In 10' it
      classifies children under developmental risk degrees. This research purpose was
      investigating BINS psychometric properties. 61 low-income Brazilian preterm, were
      divided in groups: 31 children (12 months) and 30 children (24 months), both sex,
      birth weight < 2000 g. Socio-demographic-psychological profile was previously
      registered. Neurologists examined them through Amiel-Tison and Gosselin (2001)
      and physicians with Denver-DDST-II (Frankenburg, Dodds, Archer, & Bresnick,
      1990). Psychologist assessed children at chronological age, with Bayley Scales
      BSID-II (Bayley, 1993) and BINS (12 m) and BINS (24 m). Results demonstrated
      homogeneous characteristics sample. Reliability indexes were over requested
      standards. Validity evidences based on external variables were positive moderated
      and BINS (24 m)/BSID-II (mental) presented high correlation. Validity evidences
      based on content were attested by expertise. High sensitivity was found. So, BINS
      can be considered an instrument of adequate psychometric properties, able to
      screen children under risk, according to Psychological Association requests.

PMID- 21185606
TI  - The impact of breastfeeding on mothers' attentional sensitivity towards infant
      distress.
AB  - BACKGROUND: Maternal response towards infant distress has an important impact on
      infant development. In animals it is established that lactation and pup suckling
      plays an important role in maintaining maternal responses. Previous research
      suggests that breastfeeding is associated with sensitive maternal responses in
      human mothers. However, this may be because women who are more sensitive to their
      infant choose to breastfeed. The current study investigated the attentional
      sensitivity towards infant distress in women who went on to breast or formula
      feed during pregnancy as well as after birth. We hypothesised that differences in
      breast and formula feeding mothers would only emerge after birth once feeding had
      commenced. METHOD: Women were recruited during pregnancy through community
      midwives as part of a longitudinal study. 51 women were seen during late
      pregnancy and between 3 and 6 months after birth (27 were breast and 24 were
      formula feeding). Sensitivity to infant distress was measured as the extent of
      women's attentional bias towards infant distress stimuli. RESULTS: After birth,
      we found that our index of attentional bias towards infant distress was 37 ms
      (0.5 S.D.s) (CI; 6-69, p = 0.021) higher in breastfeeding compared to formula
      feeding mothers. However, mothers who went on to breastfeed did not show greater
      attentional bias towards infant distress already during late pregnancy.
      CONCLUSIONS: Our results suggest that the act of breastfeeding may influence
      mothers' attentional sensitivity towards infant distress. Previous research
      suggests breastfeeding is indicative of sensitive parenting. The current findings
      may suggest a mechanism by which breastfeeding and/or associated infant
      interaction could contribute to this sensitivity.

PMID- 21185607
TI  - Impaired reading comprehension in schizophrenia: evidence for underlying
      phonological processing deficits.
AB  - The present study examined reading ability in high functioning people with
      schizophrenia. To this end, 16 people with schizophrenia who were living in the
      community and 12 matched controls completed tests of passage reading
      (comprehension, accuracy, and rate), word recognition, and phonological
      processing (phonological awareness, phonological memory and rapid naming) and
      ratings of reading self-concept and practices. Performance of the participants
      with schizophrenia was impaired relative to control participants on reading
      comprehension and rapid naming and relative to the population norms on
      phonological awareness, and rapid naming. In addition, self-rating data revealed
      that participants with schizophrenia had poorer perceptions of their reading
      ability and engaged in reading activities less frequently than their control
      counterparts. Consistent with earlier research, significant correlations were
      found between phonological awareness and reading comprehension. These findings
      expand on previous research in the area to suggest that community-based
      individuals with schizophrenia experience problems with reading comprehension
      that may have a phonological basis.

PMID- 21185608
TI  - Moderate increase in temperature may exacerbate neuroinflammatory processes in
      the brain: human cell culture studies.
AB  - The effect of a moderate, physiologically relevant rise in temperature on several
      neuroinflammatory parameters was investigated in vitro using human cell lines and
      cultured human astrocytes. A two degree Celsius rise in temperature was found to
      enhance the neurotoxicity of microglia-like and astrocytic cells, increase the
      release of monocyte chemotactic protein (MCP)-1 by activated human monocytic THP
      1 cells and amplify the generation of reactive oxygen intermediates by
      differentiated HL-60 myelocytic cells. Moderate increases in body temperature may
      exacerbate neuroinflammation and neuronal injury in chronic neurodegenerative
      disorders. Hence, therapies aimed at lowering the body temperature could be used
      to slow down the progression of such diseases.

PMID- 21185609
TI  - Role for tumor necrosis factor-alpha in JC virus reactivation and progressive
      multifocal leukoencephalopathy.
AB  - JCV causes the CNS demyelinating disease progressive multifocal
      leukoencephalopathy (PML). After primary infection, JCV persists in a latent
      state, where viral protein expression and replication are not detectable. NF
      kappaB and C/EBPbeta regulate the JCV promoter via a control element, kappaB,
      suggesting proinflammatory cytokines may reactivate JCV to cause PML, e.g., in
      HIV-1/AIDS. Since HIV-1 induces cytokines in brain, including TNF-alpha, we
      examined a role for TNF-alpha in JCV regulation. TNF-alpha stimulated both early
      and late JCV transcription. Further, the kappaB element conferred TNF-alpha
      response to a heterologous promoter. Immunohistochemistry of HIV+/PML revealed
      robust labeling for TNF-alpha and TNFR-1. These data suggest TNF-alpha
      stimulation of kappaB may contribute to JCV reactivation in HIV+/PML.

PMID- 21185611
TI  - Anti-TNF therapy in the injured spinal cord.
AB  - Spinal cord injury (SCI) has a significant impact on the quality and expectancy
      of life. It also carries a heavy economic burden, with considerable costs
      associated with primary care and loss of income. The normal architecture of the
      spinal cord is radically disrupted by injury. After the initial insult, structure
      and function are lost through active secondary processes that involve reactive
      astrocytes, glial progenitors, microglia, macrophages, fibroblasts and Schwann
      cells. These cells produce chemokines and cytokines such as tumor necrosis factor
      (TNF)-alpha and interleukin (IL)-1beta, which mediate the recruitment of
      inflammatory cells to the injury site. Targeting of these cytokines represents a
      potential strategy to reduce the secondary damage in SCI. In this review, we
      focus on several emerging strategies to neutralize TNF-alpha, including
      antibodies, soluble receptors, recombinant TNF-binding proteins, TNF receptor
      fusion proteins, and non-specific agents (e.g. thalidomide) and discuss their
      potential as therapy for SCI.

PMID- 21185610
TI  - Targeting the melanocortin receptor system for anti-stroke therapy.
AB  - The melanocortin receptors are a subfamily of G-protein-coupled, rhodopsin-like
      receptors that are rapidly being acknowledged as an extremely promising target
      for pharmacological intervention in a variety of different inflammatory
      pathologies, including stroke. Stroke continues to be a leading cause of death
      worldwide, with risk factors including smoking, diabetes, hypertension and
      obesity. The pathophysiology of stroke is highly complex: reintroduction of blood
      flow to the infarcted brain region is paramount in limiting ischaemic damage
      caused by stroke, yet a concomitant inflammatory response can compound tissue
      damage. The possibilities of pro-resolving treatments that target this
      inflammatory response have only recently begun to be explored. This review
      discusses the endogenous roles of the melanocortin system in reducing
      characterized aspects of inflammation, and how these, together with potent
      neuroprotective actions, suggest its potential as a therapeutic target in stroke.

PMID- 21185612
TI  - Transmurality of scar influences the effect of a hybrid-intervention with
      autologous bone marrow cell injection and aortocoronary bypass surgery (MNC/CABG)
      in patients after myocardial infarction.
AB  - BACKGROUND: Cell therapy (CTx) is a strategy to support cardiac regeneration
      after myocardial infarction (MI). Thus far, clinical studies provided mixed
      results. Here, we investigated whether transmurality of the infarct may play a
      relevant role. METHODS: 18 patients (63 +/- 3 years, 15 male) undergoing elective
      coronary artery bypass graft (CABG) surgery 2.2 +/- 0.7 months post MI
      participated. 10 had transmural and 8 non-transmural infarct scars assessed by Tc
      99m-MIBI Single-Photon Emission Computed Tomography (SPECT) and F18-FDG-Positron
      Emission-Tomography (PET). During surgery, 10 ml of sternal bone marrow were
      obtained, mononuclear cells (MNC) were isolated. At the end of surgery MNC were
      injected into the infarctions' center and border zones (10 injections, 2 ml
      total, 6.6 +/- 1.3 * 10(7) MNC). RESULTS: No major complications attributable to
      cell therapy were observed. The sizes of non-transmural scars were reduced at 3
      and 24 months after treatment (7.7 +/- 1.1% and 5.5 +/- 1.8 vs. 17.5 +/- 4.9%,
      P=0.05 and P=0.04), while transmural scars remained unchanged (23.5 +/- 2.6% and
      23.8+/-3.2 vs. 23.5 +/- 2.6%, P>0.99 and P=0.95). A trend towards improved LVEF
      was seen in patients with non-transmural scars (MRI: 48.8 +/- 5.1% vs. 30.6 +/-
      8.7%, P=0.3; SPECT: 54.1 +/- 3.1 vs. 41.0 +/- 4.0, P=0.086), but not in patients
      with transmural scars (MRI: 36.7 +/- 3.9 vs. 34.3 +/- 5.0, P=0.63, SPECT: 37.8 +/
      3.1 vs. 37.9 +/- 2.3%, P=0.96). CONCLUSIONS: A single hybrid intervention of MNC
      recovery, purification and injection with CABG-surgery (MNC/CABG) may be an
      attractive modality for cell therapy. However, no regeneration of avital
      transmural scar tissue seems to occur, while the contribution of MNC to improved
      perfusion in non-transmural myocardial infarct scars remains to be determined.

PMID- 21185614
TI  - Intracellular granule formation in response to oxidative stress in
      Bifidobacterium.
AB  - Bacteria in the genus Bifidobacterium are commonly known as beneficial colonizers
      in the human gastrointestinal tract. We found that, when these anaerobic
      organisms were grown in culture media without the reducing agent, cysteine, they
      produced intensely stained intracellular granules reminiscent of polyphosphate
      granules (poly P) produced by other bacteria in response to certain environmental
      signals, such as starvation and oxidative stress. The addition of cysteine led to
      a significant reduction in granule formation in bifidobacteria. Specific
      microscopic staining showed that the intracellular granules in Bifidobacterium
      scardovii were consistent with the poly P granules. In addition, the expression
      of the putative polyphosphate kinase gene responsible for poly P synthesis showed
      a 16-fold increase in the granule-forming cultures of B. scardovii compared with
      the nongranule-forming cultures, suggesting a role of poly P production in the
      oxidative stress response. Furthermore, the granule-forming cells exhibited a
      higher acid tolerance and a higher degree of cell surface hydrophobicity than the
      nongranule-forming cells. Therefore, we propose that Bifidobacterium cells
      produce poly P as a part of the oxidative stress response, which in turn allows
      the cells to better tolerate other environmental stresses such as acidic pH and
      perhaps allows better host colonization in vivo.

PMID- 21185613
TI  - Flat-panel versus 64-channel computed tomography for in vivo quantitative
      characterization of aortic atherosclerotic plaques.
AB  - BACKGROUND: Flat-panel computed tomography (FpCT) provides better spatial
      resolution than 64-channel CT (64-CT) and may improve in vivo quantitative
      assessment of atherosclerotic plaques. METHODS AND RESULTS: Lesions in 184 aortic
      histology sections from 6 Watanabe heritable hyperlipidemic rabbits were
      quantitatively compared with 64-CT (image thickness, 0.625 mm) and FpCT (image
      thickness, 0.150 mm) images. Images were re-oriented perpendicular to the vessel
      centerline. For detecting plaque, FpCT and 64-CT were not significantly different
      (sensitivity, 76% vs 66%; P=NS). Although FpCT was significantly more sensitive
      (42% vs 0%; P=<0.001) for detecting eccentric lesions, the area under the curve
      (AUC) for FpCT (0.6) was not significantly different from that for 64-CT (0.45;
      P=NS). In detecting plaques with <= 10% lipid (low attenuation foci), FpCT was
      significantly more sensitive than 64-CT (24% vs 0.7%; P<0.00) and had a
      significantly greater AUC (0.6 vs 0.5; P<0.006). Additionally, FpCT was more
      sensitive (65% vs 0%; P<0.00) in detecting plaques with <= 5% calcium (high
      attenuation foci) but not in detecting branch points. Both FpCT and histology
      allowed us to detect low-attenuation foci as small as 0.3mm in diameter, whereas
      64-CT allowed us to detect only low-attenuation foci >= 1.5mm in diameter.
      CONCLUSIONS: Flat-panel CT seemed to have more potential for quantitatively
      screening low-risk small atherosclerotic lesions, whereas 64-CT was apparently
      more useful when imaging established, well-characterized lesions, particularly
      when measuring the vascular wall thickness in a rabbit model of atherosclerosis.

PMID- 21185615
TI  - Glucometabolic state in Chinese patients undergoing elective coronary
      angiography.
AB  - AIM: The aim of this study is to characterize the glucometabolic state of
      patients undergoing elective coronary angiography (CA) in a subpopulation in
      China. METHODS AND RESULTS: This study recruited 896 patients undergoing elective
      CA for the evaluation of suspected coronary artery disease (CAD). Oral glucose
      tolerance tests (OGTTs) performed in patients without previously known diabetes
      revealed that 173 (19.2%) had newly diagnosed diabetes and 281 (31.5%) had
      impaired glucose regulation. The prevalence of abnormal glucose metabolism (AGM)
      was significant difference among three groups of CA diagnosis, including normal
      coronary, nonsignificant stenosis and CAD. Overall, the proportion of patients
      with type 2 diabetes increased from 22.0% at baseline to 41.2% post-OGTT
      analysis. In total, 270 (59.5%) patients with AGM would have remained undetected
      if OGTTs had not been performed. Patients with CAD, hypertension, dyslipidemia,
      obesity and high C-reactive protein levels were at high risk of AGM. CONCLUSIONS:
      AGM is common and underestimated by FPG testing alone in patients undergoing
      elective CA. OGTTs should be routinely performed to assess the glucometabolic
      state of patients undergoing elective CA, especially in patients with high risks
      of AGM. Detecting the state of AGM in CA individuals may provide strategies to
      reduce the progression of AGM and associated complications.

PMID- 21185616
TI  - Active pharmaceutical management strategies of health insurance systems to
      improve cost-effective use of medicines in low- and middle-income countries: a
      systematic review of current evidence.
AB  - OBJECTIVES: Health insurance systems have great potential to improve the cost
      effective use of medicines by leveraging better provider prescribing, more cost
      effective use by consumers, and lower prices from industry. Despite ample
      evidence from high-income countries, little is known about insurance system
      strategies targeting medicines in low- and middle-income countries (LMIC). This
      paper provides a critical review of the literature on these strategies and their
      impacts in LMIC. METHODS: We conducted a systematic review of published peer
      reviewed and grey literature and organized the insurance system strategies into
      four categories: medicines selection, purchasing, contracting and utilization
      management. RESULTS: In n=63 reviewed publications we found reasonable evidence
      supporting the use of insurance as an overall strategy to improve access to
      pharmaceuticals and outcomes in LMIC. Beyond this, most of the literature focused
      on provider contracting strategies to influence prescribing. There was very
      little evidence on medicines selection, purchasing, or utilization management
      strategies. CONCLUSIONS: There is a paucity of published evidence on the impact
      of insurance system strategies on improving the use of medicines in LMIC. The
      existing evidence is questionable since the majority of the published studies
      utilize weak study designs. This review highlights the need for well-designed
      studies to build an evidence base on the impact of medicines management
      strategies deployed by LMIC insurance programs.

PMID- 21185617
TI  - Recent developments in sociobiology and the scientific method.

PMID- 21185618
TI  - Conservation science must engender hope to succeed.

PMID- 21185619
TI  - Academic strategies in a funding crisis: research competitor, ruderal or
      university teacher?

PMID- 21185620
TI  - The application of a simplified method to map the aerobic acetate mineralization
      rates at the groundwater table of the Netherlands.
AB  - A simplified method is used to assess the microbial activity of subsoils and
      soils across a broad geographic scale. Acetate was selected because it is a major
      intermediate in catabolic biochemical pathways. In order to get minimal
      disturbance, only a small amount of tritium labelled acetate and water is added
      to the subsoil material. After an incubation time, the subsoil material is
      separated from the water by centrifugation and the formed tritium labelled water
      is separated from the remaining acetate by evaporation. The data of 128 locations
      in the Netherlands were plotted in a soil map and were also compared with the
      depth, dry weight, electric conductivity, pH and nitrate concentration. The peat
      areas consisted of limed meadows with a high groundwater level whereas the sand
      areas often showed deeper groundwater levels and a lower pH. The subsoils at the
      groundwater table of the peat areas, which are in contact with soil air, showed a
      higher mineralization rate compared with the surface soils in our study. In
      contrast, the mineralization rate of the subsoil at the groundwater table of
      sandy soils showed on average a factor 30 lower rate. Nevertheless, the self
      purification capacity of the subsoil can be vital under weather conditions where
      the surface soil becomes less active.

PMID- 21185621
TI  - Estimating spatially-variable first-order rate constants in groundwater reactive
      transport systems.
AB  - Numerical reactive transport models are often used as tools to assess aquifers
      contaminated with reactive groundwater solutes as well as investigating
      mitigation scenarios. The ability to accurately simulate the fate and transport
      of solutes, however, is often impeded by a lack of information regarding the
      parameters that define chemical reactions. In this study, we employ a steady
      state Ensemble Kalman Filter (EnKF), a data assimilation algorithm, to provide
      improved estimates of a spatially-variable first-order rate constant lambda
      through assimilation of solute concentration measurement data into reactive
      transport simulation results. The methodology is applied in a steady-state,
      synthetic aquifer system in which a contaminant is leached to the saturated zone
      and undergoes first-order decay. Multiple sources of uncertainty are
      investigated, including hydraulic conductivity of the aquifer and the statistical
      parameters that define the spatial structure of the parameter field. For the
      latter scenario, an iterative method is employed to identify the statistical mean
      of lambda of the reference system. Results from all simulations show that the
      filter scheme is successful in conditioning the lambda ensemble to the reference
      lambda field. Sensitivity analyses demonstrate that the estimation of the lambda
      values is dependent on the number of concentration measurements assimilated, the
      locations from which the measurement data are collected, the error assigned to
      the measurement values, and the correlation length of the lambda fields.

PMID- 21185622
TI  - Low-temperature-induced transcription factors in grapevine enhance cold tolerance
      in transgenic Arabidopsis plants.
AB  - We report the characterization of low-temperature-induced transcription factors
      in grapevine (Vitis vinifera). Four transcription factors were identified in low
      temperature-treated grapevine. The expression of V. vinifera C-repeat-binding
      factors, VvCBF2, VvCBF4, and VvCBFL, and V. vinifera B-box-type zinc finger
      protein, VvZFPL, was immediately induced and upregulated in leaves by the low
      temperature treatment. Similar induction of the gene expression was observed in
      low-temperature-treated stems and flowers, although VvZFPL was constitutively
      expressed in flowers. Tendrils expressed all the four genes constitutively. In
      berry skin, VvCBF2 and VvCBFL were induced by the low-temperature treatment
      before the onset of veraison, while only VvCBF2 was induced under the low
      temperature condition after the onset of veraison. The overexpression of VvCBF2
      and VvZFPL in Arabidopsis plants led to longer hypocotyls than the control
      plants. The rosette leaves of these plants were smaller and had lower chlorophyll
      contents than those of the control plants, resulting in a pale green color.
      Finally, the VvCBF2- and VvZFPL-overexpressing plants revealed growth
      retardation. These results suggest that VvCBF2 and VvZFPL may affect
      photomorphogenesis and growth in grapevine. Meanwhile, no morphological changes
      were detected in the VvCBF4- and VvCBFL-overexpressing plants. The cold tolerance
      test demonstrated that all of the overexpressing plants remained viable and
      noticeably healthy compared with the control plants even after exposure to severe
      cold treatment, suggesting that VvCBF2, VvCBF4, VvCBFL, or VvZFPL may enhance
      cold tolerance in grapevine.

PMID- 21185623
TI  - Regulation of respiration in plants: a role for alternative metabolic pathways.
AB  - Respiratory metabolism includes the reactions of glycolysis, the tricarboxylic
      acid cycle and the mitochondrial electron transport chain, but is also directly
      linked with many other metabolic pathways such as protein and lipid biosynthesis
      and photosynthesis via photorespiration. Furthermore, any change in respiratory
      activity can impact the redox status of the cell and the production of reactive
      oxygen species. In this review, it is discussed how respiration is regulated and
      what alternative pathways are known that increase the metabolic flexibility of
      this vital metabolic process. By looking at the adaptive responses of respiration
      to hypoxia or changes in the oxygen availability of a cell, the integration of
      regulatory responses of various pathways is illustrated.

PMID- 21185625
TI  - Efficient and novel one-pot synthesis of antifungal active 1-substituted-8-aryl-3
      alkyl/aryl-4H-pyrazolo[4,5-f][1,2,4]triazolo[4,3-b][1,2,4]triazepines using solid
      support.
AB  - A simple, efficient and environment-friendly procedure is developed for the
      synthesis of 1-substituted-8-aryl-3-alkyl/aryl-4H-pyrazolo[4,5
      f][1,2,4]triazolo[4,3-b][1,2,4]triazepines in the presence of N,N
      dimethylformamide as an energy transfer medium, p-TsOH as catalyst and basic
      alumina as solid support under microwave irradiation. The products are obtained
      in moderate to good yields and are in a state of high purity. Moreover, title
      compounds have been screened for antifungal activity.

PMID- 21185624
TI  - Association of common KIBRA variants with episodic memory and AD risk.
AB  - KIBRA single nucleotide polymorphism (SNP) rs17070145 was identified in a genome
      wide association study (GWAS) of memory performance, with some but not all follow
      up studies confirming association of its T allele with enhanced memory. This
      allele was associated with reduced Alzheimer's disease (AD) risk in 1 study,
      which also found overexpression of KIBRA in memory-related brain regions of AD.
      We genotyped rs17070145 and 14 additional SNPs in 2571 late onset Alzheimer's
      disease (LOAD) patients vs. 2842 controls, including African-Americans. We found
      significantly reduced risk for rs17070145 T allele in the older African-American
      subjects (p = 0.007) and a suggestive effect in the older Caucasian series. Meta
      analysis of this allele in > 8000 subjects from our and published series showed a
      suggestive protective effect (p = 0.07). Analysis of episodic memory in control
      subjects did not identify associations with rs17070145, though other SNPs showed
      significant associations in 1 series. KIBRA showed evidence of overexpression in
      the AD temporal cortex (p = 0.06) but not cerebellum. These results suggest a
      modest role for KIBRA as a cognition and AD risk gene, and also highlight the
      multifactorial complexity of its genetic associations.

PMID- 21185626
TI  - Predicting hERG activities of compounds from their 3D structures: development and
      evaluation of a global descriptors based QSAR model.
AB  - A QSAR based predictive model of hERG activity in terms of 'global descriptors'
      has been developed and evaluated. The QSAR was developed by training 77 compounds
      covering a wide range of activities and was validated based on an external 'test
      set' of 80 compounds using neural network method. Statistical parameters and
      examination of enrichment factor indicated the effectiveness of the present
      model. Randomization test demonstrated the robustness of the model and cross
      validation test further validated the QSAR. Domain of applicability test
      indicated to the high degree of reliability of the predicted results.
      Satisfactory performance in classifying compounds into 'active' and 'inactive'
      groups was also obtained. The cases where the QSAR failed, the possible sources
      of errors have been discussed.

PMID- 21185628
TI  - Neuromuscular alterations exist with knee osteoarthritis presence and severity
      despite walking velocity similarities.
AB  - BACKGROUND: Neuromuscular strategies during walking in individuals with knee
      osteoarthritis are being explored for diagnostic information; however, isolating
      differences to disease progression is difficult given walking velocity decreases
      with osteoarthritis severity. This study investigated lower extremity
      electromyograms during walking in asymptomatic individuals and individuals with
      different severities of knee osteoarthritis who walked with similar self-selected
      velocities. METHODS: Muscle activity in lateral and medial gastrocnemius, vastus
      lateralis and medialis, rectus femoris and the lateral and medial hamstrings was
      monitored during self-selected walking in 230 subjects with asymptomatic knees,
      moderate and severe knee osteoarthritis. Sixteen asymptomatic individuals, 16
      individuals with moderate and 15 individuals with severe knee osteoarthritis were
      identified based on similarities in average walking velocity. Principal component
      analysis was employed to derive amplitude and temporal characteristics of the
      electromyographic (EMG) waveforms. Analysis of variance models tested for group
      and muscle differences in principal pattern scores (alpha=0.05). Bonferroni post
      hoc testing was utilized on all significant findings. FINDINGS: Despite similar
      walking velocities, individuals with moderate knee OA had elevated and prolonged
      quadriceps and elevated lateral hamstring activity compared to asymptomatic
      individuals (P<0.05). A diminished phase shift between medial and lateral
      gastrocnemius muscle activation, greater and prolonged lateral compared to medial
      hamstring activation were found in the severe group compared to asymptomatic and
      moderate knee OA groups (P<0.05). INTERPRETATION: Lower extremity neuromuscular
      function during walking is altered with the presence and severity of knee
      osteoarthritis and not simply a direct function of walking velocity.

PMID- 21185629
TI  - Choosing a proper working length can improve the lifespan of locked plates. A
      biomechanical study.
AB  - BACKGROUND: It is hypothesized that the working length influences the implants
      fatigue behavior. However, few studies addressing this issue came to contrary
      results. Therefore, we tested systematically the influence of working length and
      implant material on the plate's endurance. METHODS: We used an artificial model
      providing the substantial angle and length conditions of a human femur. A
      fracture gap of 10mm was bridged with identical shaped plate implants made of
      stainless steel and grade-2 titanium. The fatigue strength was tested for a
      short, medium and long working length. Aiming at an implant failure within 80,000
      loading cycles the upper load threshold was set to 265N for the titanium plates
      and to 420N for the steel plates. The lower load threshold was -20N for both
      plates. FINDINGS: For the steel plates there was no correlation between fatigue
      strength and working length. The construct stiffness did not differ at short and
      medium working length and was reduced by 10% (P=0.047) at long working length.
      For the titanium plates the fatigue strength tends to increase with the working
      length but this correlation was not significant (tau=0.417, P=0.051). Further
      there was a negative correlation between working length and construct stiffness
      (tau=0.552; P=0.01). INTERPRETATION: The working length has no appreciable effect
      on the endurance of the steel plates. Compared to the grade 2-titanium plates the
      stainless steel plates sustain a larger amount of cyclic load. However, for the
      titanium plates a larger working length tends to improve the endurance.

PMID- 21185631
TI  - Strategies for enhancing the phytoremediation of cadmium-contaminated
      agricultural soils by Solanum nigrum L.
AB  - Field trials contribute practical information towards the development of
      phytoremediation strategies that cannot be provided by laboratory tests. We
      conducted field experiments utilizing the Cd hyperaccumulator plant Solanum
      nigrum L., on farmland contaminated with 1.91 mg kg(-1) Cd in the soil. Our study
      showed that S. nigrum has a relatively high biomass. Planting density had a
      significant effect on the plant biomass and thus on overall Cd accumulation. For
      double harvesting, an optimal cutting position influenced the amount of Cd
      extracted from soils. Double cropping was found to significantly increase the
      amount of Cd extracted by S. nigrum. Fertilizing had no significant effect on
      plant biomass or on the Cd remediation of the soil over the short-term period.
      Our study indicates that S. nigrum can accumulate Cd from soils where the
      concentrations are relatively low, and thus has application for use in
      decontamination of slightly to moderately Cd-contaminated soil.

PMID- 21185630
TI  - Impact of the earthworm Lumbricus terrestris (L.) on As, Cu, Pb and Zn mobility
      and speciation in contaminated soils.
AB  - To assess the risks that contaminated soils pose to the environment properly a
      greater understanding of how soil biota influence the mobility of metal(loid)s in
      soils is required. Lumbricus terrestris L. were incubated in three soils
      contaminated with As, Cu, Pb and Zn. The concentration and speciation of
      metal(loid)s in pore waters and the mobility and partitioning in casts were
      compared with earthworm-free soil. Generally the concentrations of water
      extractable metal(loid)s in earthworm casts were greater than in earthworm-free
      soil. The impact of the earthworms on concentration and speciation in pore waters
      was soil and metal specific and could be explained either by earthworm induced
      changes in soil pH or soluble organic carbon. The mobilisation of metal(loid)s in
      the environment by earthworm activity may allow for leaching or uptake into
      biota.

PMID- 21185632
TI  - HCV infection and the incidence of CKD.
AB  - BACKGROUND: The risk of hepatitis C virus (HCV) infection upon incident chronic
      kidney disease (CKD) in the presence of traditional risk factors and renal
      modifying therapy is not well known. STUDY DESIGN: National cohort study. SETTING
      & PARTICIPANTS: HCV-infected and -uninfected veterans in ERCHIVES (Electronically
      Retrieved Cohort of HCV Infected Veterans) in 2001-2006. PREDICTOR: HCV
      infection. OUTCOMES: Incident CKD stages 3-5. RESULTS: We identified 18,002
      patients with HCV infection and 25,137 controls with estimated glomerular
      filtration rate >60 mL/min/1.73 m(2) at baseline. HCV-infected patients had a
      lower prevalence of several CKD risk factors, including diabetes (22.9% vs
      26.6%), hypertension (52.4% vs 60.8%), and dyslipidemia (39.3% vs 73.9%; P <
      0.001). HCV infection was associated with a higher risk of developing CKD stages
      3-5 (HR, 1.30; 95% CI, 1.23-1.37). Increasing age, hypertension, and diabetes
      were associated with significantly higher risks of developing CKD in HCV-infected
      patients and controls. Decompensated liver disease was a strong predictor of CKD
      in HCV-infected patients (HR, 3.37; 95% CI, 3.10-3.66) and HCV-uninfected
      controls (HR, 2.04; 95% CI, 1.84-2.25). In Kaplan-Meier analysis, HCV-infected
      persons had a shorter time to CKD. LIMITATIONS: Lack of proteinuria data; small
      number of women. CONCLUSIONS: HCV infection is associated with higher risk and
      shorter time to CKD despite having a lower prevalence of many CKD risk factors.
      HCV-infected persons should have targeted monitoring for the development and
      progression of CKD.

PMID- 21185633
TI  - Social capital and self-rated health in Colombia: the good, the bad and the ugly.
AB  - Although there is increasing evidence supporting the associations between social
      capital and health, less is known of potential effects in Latin American
      countries. Our objective was to examine associations of different components of
      social capital with self-rated health in Colombia. The study had a cross
      sectional design, using data of a survey applied to a nationally representative
      sample of 3025 respondents, conducted in 2004-2005. Stratified random sampling
      was performed, based on town size, urban/rural origin, age, and sex. Examined
      indicators of social capital were interpersonal trust, reciprocity, associational
      membership, non-electoral political participation, civic activities and
      volunteering. Principal components analysis including different indicators of
      social capital distinguished three components: structural-formal (associational
      membership and non-electoral political participation), structural-informal (civic
      activities and volunteering) and cognitive (interpersonal trust and reciprocity).
      Multilevel analyses showed no significant variations of self-rated health at the
      regional level. After adjusting for sociodemographic covariates, interpersonal
      trust was statistically significantly associated with lower odds of poor/fair
      health, as well as the cognitive social capital component. Members of
      farmers/agricultural or gender-related groups had higher odds of poor/fair
      health, respectively. Excluding these groups, however, associational membership
      was associated with lower odds of poor/fair health. Likewise, in Colombians with
      educational attainment higher than high school, reciprocity was associated with
      lower odds of fair/poor health. Nevertheless, among rural respondents non
      electoral political participation was associated with worse health. In
      conclusion, cognitive social capital and associational membership were related to
      better health, and could represent important notions for health promotion. Human
      rights violations related to political violence and gender based discrimination
      may explain adverse associations with health.

PMID- 21185634
TI  - Dysfunctional social control of mental illness: a commentary on Yoon.

PMID- 21185635
TI  - Spontaneous recovery of a fronto-orbital blow-in fracture in a child.

PMID- 21185637
TI  - Transverse displacement and angulation of the proximal segment after mandibular
      setback by means of bilateral intraoral vertico-sagittal ramus osteotomy.
AB  - PURPOSE: The purpose of this study was to assess the transverse displacement and
      angulation of the proximal segment after a bilateral intraoral vertico-sagittal
      ramus osteotomy (IVSRO) and its relation with mandibular setback. PATIENTS AND
      METHODS: Sixty patients were recruited into this study and underwent a mandibular
      setback with bilateral IVSRO with wire fixation. Posteroanterior and lateral
      cephalometric radiographs were obtained 1 month before and 1 month after surgery.
      The transverse displacement and angulation of the proximal segments after surgery
      were measured on posteroanterior radiographs, via the best-fit method. The
      correlation of the amount of mandibular setback with the amount of transverse
      displacement and angulation of proximal segment was also assessed. RESULTS: A
      statistically significant increase was seen in intergonial width (P < .001), and
      inter-ramus width (P < .001) with a mean of 2.25 mm (SD, 0.82) and 4.45 mm (SD,
      1.18), respectively. Both the right and left ramus angles showed an increased
      angle on average: mean, 1.70 degrees  (SD, 0.91) and 1.43 degrees  (SD, 0.66),
      respectively. There was a statistically significant increase in both angles 1
      month after surgery (P < .001). There was a statistically significant relation
      between the amount of mandibular body setback measured at B point and increase in
      intergonial width (P = .012, r = 0.45), inter-ramus width (P = .018, r = 0.42),
      left ramus angle (P = .007, r = 0.48), and right ramus angle (P = .008, r =
      0.47). CONCLUSIONS: This study suggested that IVSRO leads to an increase in
      intergonial width and inter-ramus width, as well as the outward angulation of the
      condylar fragment. In addition, there was a significant correlation between the
      amount of setback and intergonial width, inter-ramus width, and medial ramus
      angles.

PMID- 21185636
TI  - Reconstruction of forehead skin: the unilateral horizontal advancement flap.

PMID- 21185638
TI  - Metastatic clear cell renal carcinoma of the palate mimicking noninvoluting
      congenital hemangioma.

PMID- 21185639
TI  - "Mirroring" computational planning, navigation guidance system, and
      intraoperative mobile C-arm cone-beam computed tomography with flat-panel
      detector: a new rationale in primary and secondary treatment of midfacial
      fractures?

PMID- 21185640
TI  - Nasal reconstruction: experience using tissue expansion and forehead flap.
AB  - PURPOSE: The forehead is acknowledged to be one of the best, if not the best,
      donor sites for reconstruction of postoperative nasal defects after ablation in
      cancer patients. The versatility, color match, and texture are among the benefits
      of this flap. However, it has 2 major disadvantages: 1) it is stiff, flat, and
      thicker than normal nasal skin, and thus molding from a 2-dimensional to a 3
      dimensional shape is difficult, and 2) there is a donor-site defect that requires
      coverage using a split-thickness skin graft. PATIENTS AND METHODS: In this 5-year
      study (2004-2009), we modified the 2-stage technique and added an operation
      before tissue transfer and pedicle division in 48 patients with nasal defects.
      During the first stage, the tumor was completely excised, and a tissue expander
      was inserted in the subgaleal plane. After 3 weeks, expansion was initiated. The
      second operation was performed 12 weeks later. A full-thickness forehead flap was
      elevated and transposed with primary closure of the donor site. In a third or
      final stage 3 weeks later, the pedicle was divided. Patient satisfaction and
      donor site scar was evaluated. RESULTS: Over the past 5 years, 48 reconstructions
      for nasal defects were performed using this technique. Nasal defects of the
      dorsum, alar, tip, columella, and septum were successfully treated. Graft take
      was successful in all patients. CONCLUSIONS: The forehead flap technique, in
      conjunction with tissue expander for nasal repair, has both advantages and
      disadvantages. The esthetic benefits of this technique must be weighed against
      the disadvantages.

PMID- 21185641
TI  - Technique to manage the enlarged maxillary tuberosity in elderly edentulous
      patients requiring dentures.

PMID- 21185642
TI  - Maxillomandibular advancement for obstructive sleep apnea.
AB  - Although nasal continuous positive airway pressure therapy is considered the
      first-line treatment of obstructive sleep apnea, surgery has been shown to be a
      valid option for patients who are intolerant to positive pressure therapy. In the
      past 20 years, maxillomandibular advancement has been widely accepted as the most
      effective surgical therapy for obstructive sleep apnea syndrome.
      Maxillomandibular advancement has been shown to enlarge the pharyngeal and
      hypopharyngeal airway by physically expanding the facial skeletal framework. It
      has also been shown that the forward movement of the maxillomandibular complex
      increases tissue tension. This decreases the collapsibility of the velopharyngeal
      and suprahyoid musculature and improves lateral pharyngeal wall collapse, all of
      which have been shown to be significant components contributing to the upper
      airway obstruction in obstructive sleep apnea. The outcome of maxillomandibular
      advancement has been extensively reported, with success rates of 57% to 100%. A
      recent meta-analysis of 627 patients from 22 studies showed an overall success
      rate of 86%. The long-term follow-up of 56 patients for 43.7 months from 3
      studies showed a surgical success rate of 89%. These data are similar to my
      experience with an 89% success rate in more than 600 maxillomandibular
      advancement procedures performed.

PMID- 21185643
TI  - YouTube as a source of information on cardiopulmonary resuscitation.
AB  - OBJECTIVE: Widespread knowledge of cardiopulmonary resuscitation (CPR) is
      critical to improving survival in sudden cardiac death. We analyzed YouTube, an
      Internet video-site which is a growing source of healthcare information for
      source, content and quality of information about CPR. METHODS: YouTube was
      queried using keywords "CPR", "Cardiopulmonary resuscitation", "BLS" and "Basic
      life support". Videos in English demonstrating CPR technique were included.
      Videos were classified by upload source, content, structure of course, subject
      for CPR demonstration, etc. Videos were scored for 'accuracy of demonstration' of
      CPR steps on a scale of 0-8 and for 'viewability'. RESULTS: Of 800 videos
      screened 52 met the inclusion criteria with mean duration of 233 (+/-145)s and
      view count 37 (+/-77) per day. 48% (n = 25) videos were by individuals with
      unspecified credentials. No differences were noted in view count/day, 'accuracy
      of demonstration' and 'viewability' among videos based on source. No information
      was provided about scene safety assessment in 65% (n = 34) videos. Only 69% (n =
      31/45) videos demonstrated the correct compression-ventilation ratio while 63.5%
      (n = 33), 34.6% (n = 18) and 40.4% (n = 21) gave information on location, rate
      and depth of chest compressions respectively. 19% (n = 10) videos incorrectly
      recommended checking for pulse. CONCLUSION: Videos judged the best source for CPR
      information were not the ones most viewed. Information on this platform is
      unregulated, hence content by trusted sources should be posted to provide
      accurate and easily accessible information about CPR. YouTube may have a
      potential role in video-assisted learning of CPR and as source of information for
      CPR in emergencies.

PMID- 21185644
TI  - Waterbirth and pelvic floor injury: a retrospective study and postal survey using
      ICIQ modular long form questionnaires.
AB  - OBJECTIVE: Benefits attributed to waterbirth (WB) include a shorter second stage
      of labour and reduction of perineal trauma. The aim of this study is to assess
      the incidence of perineal trauma and pelvic floor function following WB compared
      to land birth (LB). STUDY DESIGN: We conducted a retrospective analysis on the
      incidence of perineal trauma following a spontaneous WB (n=160) or a LB (n=623).
      Data were collected using the hospital's healthcare database, which codes
      information on pregnancy outcomes and related variables. ICIQ-VS for vaginal
      symptoms, and the ICIQ-KH Long Form (KHQ) were used to assess pelvic floor
      function a year after delivery. RESULTS: Length of 2nd stage was significantly
      shorter in the WB group. Although this did not translate into less perineal
      trauma, the incidence of 3rd degree tears appeared to be doubled in the WB group.
      77 (38.5%) women from the WB group and 54 (22%) from the LB group answered the
      postal questionnaires. A significant number of women reported vaginal and urinary
      symptoms, however the difference between both groups was not statistically
      significant. CONCLUSION: Waterbirth results in a shorter 2nd stage of labour.
      This does not lead to less overall perineal trauma or better pelvic floor
      performance postpartum. Physical limitations in protecting the perineum during
      the expulsion phase may be associated with an increase in the incidence of 3rd
      degree tears in the WB population.

PMID- 21185645
TI  - Acute toxicity evaluation of explosive wastewater by bacterial bioluminescence
      assays using a freshwater luminescent bacterium, Vibrio qinghaiensis sp. Nov.
AB  - The compositions of explosive wastewater generated from TNT (2,4,6
      trinitrotoluene) purification stage were characterized by using UV-vis
      spectroscopy, Fourier transform infrared spectroscopy (FTIR), high performance
      liquid chromatograph (HPLC) and gas chromatograph/mass spectroscopy (GC/MS). The
      acute toxicity was evaluated by bacterium bioluminescence assay using a
      freshwater luminescent bacterium (Vibrio qinghaiensis sp. Nov.) and a marine
      luminescent bacterium (Photobacterium phosphoreum). The results showed that the
      wastewater's biodegradability was poor due to the high amount of chemical oxygen
      demand (COD). The main organic components were dinitrotoluene sulfonates (DNTS)
      with small amount of TNT, dinitrotoluene (DNT), mononitrotoluene (MNT) and other
      derivatives of nitrobenzene. It was highly toxic to luminescent bacteria P.
      phosphoreum and V. qinghaiensis sp. Nov. After reaction time of 15 min, the
      relative concentration of toxic pollutants (expressed as reciprocal of dilution
      ratio of wastewater) at 50% of luminescence inhibition ratio was 5.32*10(-4) for
      P. phosphoreu, while that was 4.34*10(-4) for V. qinghaiensis. V. qinghaiensis is
      more sensitive and suitable for evaluating the wastewater's acute toxicity than
      P. phosphoreum. After adsorption by resin, the acute toxicity can be greatly
      reduced, which is helpful for further treatment by biological methods.

PMID- 21185646
TI  - A new approach to simulate characterization of particulate matter employing
      support vector machines.
AB  - This paper, for the first time, applies the support vector machines (SVMs)
      paradigm to identify the optimal segmentation algorithm for physical
      characterization of particulate matter. Size of the particles is an essential
      component of physical characterization as larger particles get filtered through
      nose and throat while smaller particles have detrimental effect on human health.
      Typical particulate characterization processes involve image reading,
      preprocessing, segmentation, feature extraction, and representation. Of these
      various steps, knowledge based selection of optimal image segmentation algorithm
      (from existing segmentation algorithms) is the key for accurately analyzing the
      captured images of fine particulate matter. Motivated by the emerging machine
      learning concepts, we present a new framework for automating the selection of
      optimal image segmentation algorithm employing SVMs trained and validated with
      image feature data. Results show that the SVM method accurately predicts the best
      segmentation algorithm. As well, an image processing algorithm based on Sobel
      edge detection is developed and illustrated.

PMID- 21185647
TI  - Novel zwitterionic inorganic-organic hybrids: synthesis of hybrid adsorbents and
      their applications for Cu2+ removal.
AB  - A series of zwitterionic hybrid adsorbents were prepared via the ring-opening
      polymerization of pyromellitic acid dianhydride (PMDA) and N-[3
      (trimethoxysilyl)propyl] ethylene diamine (TMSPEDA), and a subsequent
      zwitterionic process as well as sol-gel reaction. Their applications for Cu(2+)
      removal by adsorption were performed. FTIR spectra confirmed the step products.
      TGA revealed that the initial decomposition temperature (IDT) of these
      zwitterionic hybrid adsorbents could arrive at near 150 degrees C. DSC showed
      that T(g) values decreased with an increase in PMDA content in the hybrid matrix.
      Ion-change capacity (IEC) revealed that the cation-exchange capacities (CIECs)
      and anion-exchange capacities (AIECs) of these hybrid adsorbents were within the
      range of 9.13-11.49 and 4.97-6.28 mmol g(-1), respectively. Meanwhile, the CIECs
      and AIECs exhibit an opposite change trend as PMDA content increases. Adsorption
      experiment indicated that their adsorptions for Cu(2+) ions followed Lagergren
      second-order kinetic model, surface adsorption and intraparticle diffusion
      mechanisms might be the major process. These findings demonstrated that they are
      promising absorbents for the separation and recovery of Cu(2+) ions from
      contaminated water.

PMID- 21185648
TI  - Silkworm exuviae--a new non-conventional and low-cost adsorbent for removal of
      methylene blue from aqueous solutions.
AB  - In this paper, silkworm exuviae (SE) waste, an agricultural waste available in
      large quantity in China, was utilized as low-cost adsorbent to remove basic dye
      (methylene blue, MB) from aqueous solution by adsorption. Kinetic data and
      sorption equilibrium isotherms were carried out in batch process. The adsorption
      kinetic experiments revealed that MB adsorption onto SE for different initial dye
      concentrations all followed pseudo-second order kinetics and were mainly
      controlled by the film diffusion mechanism. Batch equilibrium results at
      different temperatures suggest that MB adsorption onto SE can be described
      perfectly with Freundlich isotherm model compared with Langmuir and D-R isotherm
      models, and the characteristic parameters for each adsorption isotherm were also
      determined. Thermodynamic parameters calculated show the adsorption process has
      been found to be endothermic in nature. The analysis for the values of the mean
      free energies of adsorption (E(a)), the Gibbs free energy (DeltaG(0)) and the
      effect of ionic strength all demonstrate that the whole adsorption process is
      mainly dominated by ion-exchange mechanism, which has also been verified by
      variations in FT-IR spectra and pH value before and after adsorption and
      desorption studies. The results reveal that SE can be employed as a low-cost
      alternative to other adsorbents for MB adsorption.

PMID- 21185650
TI  - On the relationship between nociceptive evoked potentials and intraepidermal
      nerve fiber density in painful sensory polyneuropathies.
AB  - This study analyzed the relationship between the density of intraepidermal nerve
      fibers (IENF) and the characteristics of either nociceptive laser-evoked
      potentials (LEPs) or contact heat-evoked potentials (CHEPs) in patients with
      painful sensory polyneuropathy with the aim to determine which parameters of LEPs
      and CHEPs more reliably reflect IENF loss. A total of 96 patients and 35 healthy
      volunteers took part in the study. Based on clinical examination, nerve
      conduction tests, and quantitative sensory testing, we identified 52 patients
      with small-fiber neuropathy (SFN), 40 with mixed (small-fiber and large-fiber)
      neuropathy (MFN), and 4 who were excluded from the analysis because of no
      evidence of involvement of small fibers. The latency of the N2 was delayed for
      both LEPs and CHEPs in patients with MFN and for CHEPs only in patients with SFN.
      The amplitude of the vertex N2/P2 potential was similarly reduced in both types
      of neuropathy, but LEPs were more frequently absent than CHEPs in MFN patients
      (68% vs 40%). In general, latency and amplitude of LEPs and CHEPs were well
      correlated with IENF density. SFN patients were characterized by abnormal EPs and
      slightly decreased but morphologically abnormal IENF. MFN patients were
      characterized by frequently absent LEPs and CHEPs and a rather severe IENF loss.
      The correlation between nociceptive evoked potentials (laser-evoked potentials
      and contact heat-evoked potentials) and skin biopsy aids in the diagnosis of
      painful neuropathies.

PMID- 21185649
TI  - Local application of the endocannabinoid hydrolysis inhibitor URB597 reduces
      nociception in spontaneous and chemically induced models of osteoarthritis.
AB  - The present study examined whether enhancement of endogenous cannabinoid levels
      by administration of the fatty acid amide hydrolase inhibitor URB597 could
      modulate joint nociception in 2 rodent models of osteoarthritis (OA). OA-like
      changes were induced in male Wistar rats by intra-articular injection of
      monoiodoacetate, while Dunkin-Hartley guinea pigs (age 9-12 months) develop OA
      naturally and were used as a model of spontaneous OA. Joint nociception was
      measured by recording electrophysiologically from knee joint primary afferents in
      response to noxious hyper-rotation of the joint before and after close intra
      arterial injection of URB597 (0.03 mg; 0.1 mL bolus); the CB(1) receptor
      antagonist AM251 (1 mg/kg intraperitoneally) or the CB(2) receptor antagonist
      AM630 (1 mg/kg intraperitoneally). The effect of systemic URB597 administration
      (5 mg/kg) on joint pain perception in the monoiodoacetate model was determined by
      hindlimb incapacitance. Peripheral injection of URB597 caused afferent firing
      rate to be significantly reduced by up to 56% in the rat OA model and by up to
      69% in the guinea pig OA model. Systemic co-administration of AM251, but not
      AM630, abolished the antinociceptive effect of URB597 in both models. URB597 had
      no effect in saline-injected control rat joints or in nonarthritic guinea pigs.
      Systemic URB597 administration significantly reduced hindlimb incapacitance in
      monoiodoacetate joints and co-administration of the CB(1) antagonist abolished
      this effect. Local injection of URB597 into OA knee joints reduces
      mechanonociception and pain, and this response is mediated by CB(1) receptors.
      Targeting endocannabinoid-metabolizing enzymes in the peripheral nervous system
      could offer novel therapeutic approaches for the treatment of OA pain.

PMID- 21185651
TI  - Atomic imaging using secondary electrons in a scanning transmission electron
      microscope: experimental observations and possible mechanisms.
AB  - We report detailed investigation of high-resolution imaging using secondary
      electrons (SE) with a sub-nanometer probe in an aberration-corrected transmission
      electron microscope, Hitachi HD2700C. This instrument also allows us to acquire
      the corresponding annular dark-field (ADF) images both simultaneously and
      separately. We demonstrate that atomic SE imaging is achievable for a wide range
      of elements, from uranium to carbon. Using the ADF images as a reference, we
      studied the SE image intensity and contrast as functions of applied bias, atomic
      number, crystal tilt, and thickness to shed light on the origin of the unexpected
      ultrahigh resolution in SE imaging. We have also demonstrated that the SE signal
      is sensitive to the terminating species at a crystal surface. A possible
      mechanism for atomic-scale SE imaging is proposed. The ability to image both the
      surface and bulk of a sample at atomic-scale is unprecedented, and can have
      important applications in the field of electron microscopy and materials
      characterization.

PMID- 21185652
TI  - Spatial and temporal investigation of Echinococcus granulosus coproantigen
      prevalence in farm dogs in South Powys, Wales.
AB  - The prevalence of canine echinococcosis appears to have been increasing in
      mid/south Wales in recent years - raising the concern of a potential resurgence
      in transmission to humans. A campaign was therefore conducted in 2008 in order to
      provide dogs in South Powys with anthelmintics, estimate the coproantigen
      prevalence amongst these dogs, and evaluate potential risk factors for
      coproantigen positivity. The coproantigen prevalence identified in these dogs
      (n=577) was 10.6% (95% confidence interval 7.6-13.5%), with 20.6% (15.6-25.7%) of
      farms (n=247) containing at least one coproantigen-positive dog. Further spatial
      investigation identified considerable spatial heterogeneity amongst the farms,
      with an increased coproantigen prevalence in the regions of Brecknockshire and
      the Brecon Beacons National Park. Within these areas, there was strong evidence
      of an increase in coproantigen prevalence, compared to that found in a study
      conducted in 2002. Finally, a mixed effects logistic regression model identified
      increased roaming behaviour and decreased dog weight as being associated with
      increased odds of coproantigen positivity, whereas pet dogs on some farms had
      similar odds of infection to working dogs. Further surveillance efforts in South
      Powys are required and should also include the northern areas of Gwent and
      Glamorgan.

PMID- 21185653
TI  - A longitudinal study of Besnoitia besnoiti infections and seasonal abundance of
      Stomoxys calcitrans in a dairy cattle farm of southwest France.
AB  - Bovine besnoitiosis, caused by the cyst-forming apicomplexan Besnoitia besnoiti,
      is commonly reported in some restricted regions of South-Western Europe, and in
      larger regions of Africa and Asia. This infection is thought to be transmitted by
      blood feeding insects and is responsible for major economic losses in cattle
      production. A recent emergence in Europe, notified in the Centre of France, Spain
      and Germany, has attracted more attention to this disease. Clinical signs could
      appear in some animals; however, many infected cattle remain asymptomatic or show
      scleral-conjunctival cysts (SCC) only. Recent development of serological methods
      allows carrying out seroepidemiological field studies. In this respect, a long
      term investigation was performed in a dairy cattle farm localized in an enzootic
      area of besnoitiosis of South-western France between March 2008 and May 2009. The
      objective was to estimate the seasonal pattern of B. besnoiti infections based on
      the presence of SCC and serology (ELISA and Western blot). In parallel, an
      entomological survey was conducted to describe population dynamics of Stomoxys
      calcitrans and Tabanidae species. The seroprevalence determined by Western blot
      in a cohort of 57 animals continuously present during the whole survey increased
      from 30% in March 2008 to 89.5% in May 2009 and was always higher than the
      prevalence based on clinically assessed SCC. New positive B. besnoitia
      seroconversions occurred throughout the year with the highest number in spring.
      In addition, many seroconversions were reported in the two months before turn-out
      and could be associated with a high indoors activity of S. calcitrans during this
      period.

PMID- 21185654
TI  - Influence of culture medium pH on internalization, growth and phenotypic
      plasticity of Neospora caninum.
AB  - Neospora caninum, a strictly intracellular protozoan, is a major leading cause of
      parasite-induced abortion in cattle. A widely held view of N. caninum infection
      is that both cellular proliferation and stage interconversion (tachyzoite
      bradyzoite transformation) are triggered, perhaps even modulated by, changes in
      cultural conditions. This study tested the hypothesis that exposure of N. caninum
      tachyzoites to different pH culture media affects the parasite's entry,
      proliferation and cyst formation in cultured cells. The endocytic pathway for N.
      caninum entry into the K562 cell line was found to be mediated by low pH of
      culture medium. Internalization of N. caninum by host cells was significantly
      increased in acidic and alkaline culture medium compared to cells maintained in
      neutral medium as revealed by transmission electron microscopy. Parasite
      proliferation within Vero cells was assessed by plaque formation assay and was
      found to be highest when pH level was optimum, paralleled by a decrease in the
      number of cysts. In contrast, parasite encystation increased when the pH level
      was alkaline or acidic, as evaluated by indirect immunofluorescence and
      immunocytochemical analyses. Acidic pH regardless of state of host cell infection
      suppressed the rate of host cell division. These findings suggest that culture
      medium pH has a determinable effect on the host cell-N. caninum interaction and
      support the hypothesis that pH of culture medium influence the entry, growth, and
      phenotypic plasticity of N. caninum in mammalian cells.

PMID- 21185656
TI  - The role of assisted self-help in services for alcohol-related disorders.
AB  - Potentially harmful substance use is common, but many affected people do not
      receive treatment. Brief face-to-face treatments show impact, as do strategies to
      assist self-help remotely, by using bibliotherapies, computers or mobile phones.
      Remotely delivered treatments offer more sustained and multifaceted support than
      brief interventions, and they show a substantial cost advantage as users increase
      in number. They may also build skills, confidence and treatment fidelity in
      providers who use them in sessions. Engagement and retention remain challenges,
      but electronic treatments show promise in engaging younger populations.
      Recruitment may be assisted by integration with community campaigns or brief
      opportunistic interventions. However, routine use of assisted self-help by
      standard services faces significant challenges. Strategies to optimize adoption
      are discussed.

PMID- 21185655
TI  - Life long endogenous estrogen exposure and later adulthood cognitive function in
      a population of naturally postmenopausal women from Southern China: the Guangzhou
      Biobank Cohort Study.
AB  - BACKGROUND: Estrogen has neurotrophic and neuroprotective properties in animal
      and in vitro studies. Epidemiological studies are inconclusive, but suggest a
      positive association between endogenous estrogen exposure (measured by
      reproductive period, the number of years between menarche and menopause) and
      later life cognitive function. METHODS: Structural equation modeling was used in
      a cross-sectional study of 11,094 naturally postmenopausal multiparous Chinese
      older (>=50 years) women from the Guangzhou Biobank Cohort Study (phases 2 and 3)
      to assess the interrelationship of four proxies of higher endogenous estrogen
      exposure (longer reproductive period, older age of first pregnancy, lower parity
      and shorter average duration of breast feeding per child) with immediate and the
      delayed 10-word recall score in phases 2 and 3, and with the mini-mental state
      examination (MMSE) score in phase 3 (5641 women). RESULTS: Adjusted for age,
      education, childhood and adulthood socio-economic position and physical activity,
      longer reproductive period was associated with higher scores (0.02 words per
      year, 95% confidence interval (CI) 0.008-0.02 for delayed recall and 0.05 MMSE
      score, 95%CI 0.04-0.07, respectively). Lower parity and shorter average duration
      of breast-feeding per child were also associated with better cognitive function.
      CONCLUSIONS: In a large cohort of naturally postmenopausal Chinese women proxies
      of greater endogenous estrogen exposure were associated with better cognitive
      function. These findings support biological evidence for a cognitively protective
      role of endogenous estrogen.

PMID- 21185657
TI  - Proximal atherosclerotic lesion as a cause of very late stent thrombosis.
AB  - Very late stent thrombosis is defined as in-stent thrombosis occurring after 1
      year of an intra-coronary artery stent placement. Drug eluting stents have lately
      been criticized for increased reports of very late stent thrombosis. The exact
      cause of these very late stent thromboses is not clearly understood. Virchow's
      triad describes the three main factors of thrombus formation to be stasis of
      blood flow, endothelial injury and hypercoagulability. Based on Virchow's triad,
      we propose the cause of very late stent thrombosis to be formation of a de novo
      atherosclerotic lesion in the proximal segment of a stented artery. The de novo
      atherosclerotic lesion narrows the vessel lumen and causes stasis of blood flow
      in the distal stent. The de novo lesion can also cause myocardial ischemia
      creating a prothrombotic environment in the stented region. Stasis of blood flow
      and prothrombotic environment in the stented region can lead to the formation of
      very late stent thrombosis. Since atherosclerosis is a dynamic aging process in
      humans, we propose de novo proximal lesions in the coronary arteries can
      predispose to very late stent thrombosis.

PMID- 21185658
TI  - Physico-chemical, microbiological, textural and sensory attributes of matured
      game salami produced from springbok (Antidorcas marsupialis), gemsbok (Oryx
      gazella), kudu (Tragelaphus strepsiceros) and zebra (Equus burchelli) harvested
      in Namibia.
AB  - Differences and consumer acceptability of matured salami produced from game
      species were evaluated. The pH of the salami differed (p < 0.05) with springbok
      salami having the highest mean pH value. No differences (p > 0.05) were observed
      among the species for a(w), shear force, gumminess or cohesiveness.
      Microbiological counts of the game salami differed for coliform (p < 0.05) but
      not for E. coli (p > 0.05) counts. The most distinctive characteristics observed
      by the quantitative descriptive analyses were smoky, salty, pepper and salami
      flavour, combined with a smoky, salami aroma. Game flavour was not perceived as a
      strong attribute during the sensory analyses. Gemsbok salami was strongly
      associated with the attribute colour as described by the male and female consumer
      panels. The springbok salami scored the lowest for both colour and taste. Salami
      produced from gemsbok, kudu and zebra were superior to springbok salami.

PMID- 21185659
TI  - Cookery method and end-point temperature can affect the Warner-Bratzler shear
      force, cooking loss, and internal cooked color of beef longissimus steaks.
AB  - Steaks from 60 beef ribeye rolls were used to test the interactive effects of
      cookery method and end-point temperature on Warner-Bratzler shear force (WBSF)
      and internal cooked color. Pairs of longissimus thoracis (LT) steaks were
      assigned to combinations of 3 different end-point temperatures and 5 cookery
      methods. The forced-air convection oven (FAC) required the longest time and
      produced the reddest internal color, regardless of end-point temperature. The
      clam-shell grill (CLAM) required the least cooking time and resulted in the
      lowest cooking losses, but CLAM-cooked steaks also had the greatest WBSF values
      and least red internal color. Repeatability values for WBSF were acceptable
      (>0.60) for all degrees of doneness when steaks were cooked in the FAC and
      impingement oven, but steaks cooked on the CLAM were not repeatable. The
      relationship of myofibrillar toughening, moisture loss and cooked color changes
      in beef LT steaks also differed due to cookery methods.

PMID- 21185660
TI  - Alexithymia in alcohol dependent patients is partially mediated by alcohol
      expectancy.
AB  - BACKGROUND: Up to fifty percent of alcohol dependent individuals have
      alexithymia, a personality trait characterised by difficulties identifying and
      describing feelings, a lack of imagination and an externalised cognitive style.
      Although studies have examined alexithymia in relation to alcohol dependence, no
      research exists on mechanisms underlying this relationship. The present study
      examined the mediational effect of alcohol expectancies on alexithymia and
      alcohol dependence. METHODS: 230 outpatients completed the Toronto Alexithymia
      Scale (TAS-20), the Drinking Expectancy Questionnaire (DEQ) and the Alcohol Use
      Disorder Identification Test (AUDIT). RESULTS: Regression analysis showed that
      alexithymia and alcohol dependence was, in two of three cases, partially mediated
      through alcohol expectancy. CONCLUSIONS: Alcohol expectancies of assertion and
      affective change show promise as mediators of alcohol dependence in individuals
      with alexithymia.

PMID- 21185661
TI  - Fetal response to abbreviated relaxation techniques. A randomized controlled
      study.
AB  - BACKGROUND: stress during pregnancy can have adverse effects on the course of
      pregnancy and on fetal development. There are few studies investigating the
      outcome of stress reduction interventions on maternal well-being and obstetric
      outcome. AIMS: this study aims (1) to obtain fetal behavioral states
      (quiet/active sleep, quiet/active wakefulness), (2) to investigate the effects of
      maternal relaxation on fetal behavior as well as on uterine activity, and (3) to
      investigate maternal physiological and endocrine parameters as potential
      underlying mechanisms for maternal-fetal relaxation-transferral. STUDY DESIGN:
      the behavior of 33 fetuses was analyzed during laboratory relaxation/quiet rest
      (control group, CG) and controlled for baseline fetal behavior. Potential
      associations between relaxation/quiet rest and fetal behavior (fetal heart rate
      (FHR), FHR variation, FHR acceleration, and body movements) and uterine activity
      were studied, using a computerized cardiotocogram (CTG) system. Maternal heart
      rate, blood pressure, cortisol, and norepinephrine were measured. RESULTS:
      intervention (progressive muscle relaxation, PMR, and guided imagery, GI) showed
      changes in fetal behavior. The intervention groups had higher long-term variation
      during and after relaxation compared to the CG (p=.039). CG fetuses had more FHR
      acceleration, especially during and after quiet rest (p=.027). Women in the PMR
      group had significantly more uterine activity than women in the GI group (p=.011)
      and than CG women. Maternal heart rate, blood pressure, and stress hormones were
      not associated with fetal behavior. CONCLUSIONS: this study indicates that the
      fetus might participate in maternal relaxation and suggests that GI is superior
      to PMR. This could especially be true for women who tend to direct their
      attention to body sensations such as abdominal activity.

PMID- 21185662
TI  - Applications of a transportable Raman spectrometer for the in situ detection of
      controlled substances at border controls.
AB  - A transportable Raman spectrometer was tested for the detection of illicit drugs
      seized during border controls. In a first step, the analysis methodology was
      optimized using reference substances such as diacetylmorphine (heroin), cocaine
      and amphetamine (as powder or liquid forms). Adequate focalisation distance and
      times of analysis, influence of daylight and artificial light sources,
      repeatability and limits of detection were studied. In a second step, the
      applications and limitations of the technique to detect the illicit substances in
      different mixtures and containers were evaluated. Transportable Raman
      spectroscopy was found to be adequate for a rapid screen of liquids and powders
      for the detection and identification of controlled substances. Additionally, it
      had the advantage over other portable techniques, such as ion mobility
      spectrometry, of being non-destructive and capable of rapid analysis of large
      quantities of substances through containers such as plastic bags and glass
      bottles.

PMID- 21185663
TI  - [Rupture of a popliteal artery pseudo-aneurysm revealing a tibial osteochondroma:
      case report and review of the literature].
AB  - Osteochondroma constitutes the most frequent bone tumor. It is exceptionally
      responsible for vascular complications from which pseudo-aneurysms constitute the
      most frequent entity. We report the case of a 20-year-old patient who presented
      with acute pain of the left knee following a sports' accident. Vascular
      ultrasonography showed the rupture of a false aneurysm of the popliteal artery.
      An arteriography confirmed the diagnosis by showing contrast leakage at the level
      of the below-knee popliteal artery projecting over an osteochondroma. Surgery was
      undertaken to close the aneurysm an insert a venous graft. The procedure was
      completed by excision of the bone tumor. Vascular complications of osteochondroma
      are rare but should be considered in young patients with a false aneurysm of the
      popliteal artery. Surgery is required for the treatment of false aneurysms on
      exostosis.

PMID- 21185664
TI  - Adjuvant radiotherapy for rectal cancer: recent results, new questions.
AB  - Many randomised studies have now well established the role of radiotherapy (RT)
      in rectal cancer: it decreases the rate of local relapse and improves survival
      for stage II and III. The benefit of RT remains even in case of total mesorectum
      excision. Preoperative strategy has a better tolerance and is more efficient than
      post-operative RT. Two schedules have been widely used: an hypofractionated (5 *
      5 Gy) and a normofractionated (45-50 Gy by fractions of 1.8-2 Gy) schedule. Both
      have advantages and drawbacks. Patients with locally advanced tumours or low
      lying cancer must benefit from a protracted schedule, which increases down
      staging and the number of sphincter-preserving surgery. Combined
      chemoradiotherapy with 5FU or capecitabine enhances local control without a clear
      benefit in overall survival or disease-free survival. Adjunction of oxaliplatin
      does not improve the pathological response rate significantly. Results with
      cetuximab are still disappointing. Bevacizumab seems to increase widely the
      radiation response, but more data are needed to confirm these preliminary
      results. With this modern approach, the rate of local relapse is lower than 10%;
      the main issue is now the occurrence of distant relapses in 25-30% of the
      patients. Neo-adjuvant chemotherapy (CT) seems the better way to address this
      issue, because post-operative CT could be done properly in only 50% of the
      patients. Large prospective trials using neo-adjuvant CT with or without targeted
      therapies must be designed taking distant relapses and overall survival as main
      end-points.

PMID- 21185665
TI  - Bilateral patellar tendon ruptures without predisposing systemic disease or
      steroid use: a case report and review of the literature.
AB  - Simultaneous bilateral patellar tendon rupture occurs rarely and is even rarer in
      patients without systemic disease or predisposing conditions. We present a case
      of bilateral, midsubstance patellar tendon ruptures along with a partial anterior
      cruciate ligament tear from a fall from a standing height in an otherwise healthy
      adult without any predisposing conditions. Most patients that sustain a tendon
      rupture have risk factors for tendonopathy including chronic renal disease,
      systemic lupus erythematosus, rheumatoid arthritis, or exposure to medications
      (such as corticosteroids or fluoroquinolones). Currently, there are approximately
      50 reported cases of bilateral patellar tendon rupture in the scientific
      literature; however, only a small minority occurred in patients without any
      predisposing factors. Most of the reports of a bilateral tendon rupture without
      systemic disease occurred in the inferior pole of the tendon, with only a few of
      these occurring in the midsubstance. Because of the rarity of this event in a
      patient without systemic disease, this condition is often misdiagnosed. Emergency
      physicians should maintain a high degree of suspicion in those patients with
      concerning clinical and/or radiographic findings.

PMID- 21185666
TI  - Tension pneumoperitoneum during routine colonoscopy.
AB  - Colonoscopy is generally a safe and effective means to detect, diagnose, and
      treat colonic abnormalities. Although the overall complication rate is low, the
      morbidity and mortality following perforation approach 50%. Here we present a
      case of a 49-year-old woman undergoing routine colonoscopy when she suffered
      bowel perforation and tension pneumoperitoneum. This is a seldom occurrence and
      may result following bowel perforation with the rapid accumulation of free air
      into the peritoneal cavity. It is a life-threatening complication and a surgical
      emergency.

PMID- 21185667
TI  - Bedside renal ultrasound in the evaluation of suspected ureterolithiasis.
AB  - OBJECTIVE: To determine whether ultrasound changes emergency physicians'
      estimated likelihood of acute ureterolithiasis in patients with flank pain.
      METHODS: This prospective, observational study enrolled patients awaiting
      computed tomographic (CT) scan for presumed renal colic. Using a visual analogue
      scale, treating physicians estimated the likelihood of acute ureterolithiasis
      based first on clinical findings and urinalysis, then after ultrasound, and
      finally after CT. A 20% change in estimated likelihood was considered clinically
      significant. Test characteristics of ultrasound for any ureteral stone and for
      those greater than or equal to 5 mm in size were determined. RESULTS: One hundred
      seven patients were enrolled. Sensitivity, specificity, and negative predictive
      value of ultrasound for stones observed on CT were 76.3% (95% confidence interval
      [CI], 59.4%-88.0%), 78.3% (95% CI, 66.4%-86.9%), and 85.7% (95% CI, 74.1%-92.9%)
      respectively, and for stones >5 mm 90.0% (95% CI, 54.1%-99.5%), 63.9% (95% CI,
      53.4%-73.2%), and 98.4% (95% CI, 90.3%-99.9%), respectively. Ultrasound
      significantly impacted the estimated likelihood of disease in 33 of 107 cases
      (30.8%, 95% CI, 22.5%-40.6%). Computed tomography further significantly changed
      physicians' impression of disease in 55 of 107 cases (51.4%, 95% CI, 41.6%
      61.1%). CONCLUSIONS: Bedside renal ultrasound had only a limited impact on the
      physicians' clinical impression of patients with possible ureterolithiasis. The
      sensitivity of sonographic hydronephrosis was modest for detecting any ureteral
      stone, but much better for detecting a large stone. Further study is needed to
      define the precise role ultrasound should play in evaluating patients with
      suspected ureterolithiasis.

PMID- 21185668
TI  - Elevated S100B level in cerebrospinal fluid could predict poor outcome of carbon
      monoxide poisoning.
AB  - OBJECTIVE: S100B is a calcium-binding protein produced by astroglia in the brain
      and has been used as a marker of neuronal damage after brain trauma. We
      investigated the utility of S100B in cerebrospinal fluid (CSF) measured during
      the early phase of carbon monoxide (CO) poisoning in predicting the subsequent
      clinical course. METHODS: The study included 31 patients who were admitted to the
      hospital with loss of consciousness following CO poisoning. S100B levels were
      measured by enzyme-linked immunosorbent assay in CSF, and serum samples collected
      simultaneously within 24 hours and on the fourth day after CO exposure. All
      patients were followed for at least 3 months and divided into 3 groups based on
      the clinical course: persistent vegetative state (PVS), delayed encephalopathy
      (DE), and complete recovery with no complications (NC). RESULTS: During the 3
      month period, 3 patients developed PVS, 5 developed DE, and 23 were classified as
      NC. The mean S100B levels in the CSF within 24 hours after CO exposure were
      higher in the PVS group (9.25 ng/mL) than in the DE (2.03 ng/mL) and NC groups
      (1.86 ng/mL). However, the mean serum S100B levels were not elevated in the 3
      groups (0.21, 0.59, and 0.16 ng/mL, respectively). CONCLUSION: Early elevation of
      S100B in CSF after CO poisoning could be a suitable predictor of subsequent
      development of PVS.

PMID- 21185669
TI  - Capitellum fracture: detecting fat pads may have a significant impact on outcome.
AB  - Capitellum fractures account for less than 1% of all elbow fractures. Their
      appearance on plain radiographs may be subtle. It is this combination of features
      that make these injuries easy to misdiagnose. Misdiagnosis of a nondisplaced
      capitellum fracture is significant because the capitellum does not have soft
      tissue attachments and can convert to a displaced fracture that will need
      surgery. Although a prior study has reported a high incidence of occult elbow
      fractures when elevated fat pads are present, it did not demonstrate an impact on
      management. Our case illustrates that because of the capitellum's propensity to
      displace, detecting fat pads and immobilizing the elbow may have a significant
      impact on outcome.

PMID- 21185670
TI  - Do outcomes of near syncope parallel syncope?
AB  - BACKGROUND: Limited information on the evaluation of emergency department (ED)
      patients complaining of "near syncope" exists. Multiple studies of syncope
      exclude near syncope claiming near syncope is poorly defined and its definition
      is nonuniform. OBJECTIVE: The aim of this study was to determine the incidence of
      critical interventions or adverse outcomes associated with near syncope and
      compare these outcomes with syncope. METHODS: Prospective, observational study
      enrolling (August 2007-October 2008) consecutive ED patients (age, >=18 years)
      presenting with near syncope was conducted. Near syncope was defined as an
      episode in which the patient felt they might lose consciousness but did not.
      Critical intervention/adverse outcome was defined as hemorrhage, cardiac
      ischemia/intervention, alteration in antidysrhythmics, pacemaker/defibrillator
      placement, sepsis, stroke, death, dysrhythmia, sepsis, pulmonary embolus, or
      carotid stenosis. Primary outcome was an adverse outcome or critical intervention
      in hospital or less than 30 days. Near syncope and syncope outcomes and admission
      rates were compared using the chi(2) test. RESULTS: After 1870 patients were
      screened, 244 met the study definition. Of the 244 patients, follow-up was
      achieved in 242 (99%). Emergency department hospitalization or 30-day adverse
      outcomes occurred in 49 (20%) of 244 compared with 68 (23%) of 293 of patients
      with syncope (P = .40). The most common adverse outcomes/critical interventions
      were hemorrhage (n = 6), bradydysrhythmia (n = 6), alteration in antidysrhythmics
      (n = 6), and sepsis (n = 10). Of patients with near syncope, 49% were admitted
      compared with 69% with syncope (P = .001). CONCLUSION: Patients with near syncope
      are as likely those with syncope to experience critical interventions or adverse
      outcomes; however, near-syncope patients are less likely to be admitted. Given
      similar risk of adverse outcomes for near syncope and syncope, future studies are
      warranted to improve the treatment of ED patients with near syncope.

PMID- 21185671
TI  - Left ventricular dysfunction screening in hypertensive patients with N-terminal
      pro-B-type natriuretic peptide and electrocardiogram.
AB  - OBJECTIVE: Early recognition of left ventricular hypertrophy is important because
      antihypertensive treatment decreases morbidity and mortality. The ideal screening
      method for left ventricular hypertrophy in hypertensive emergency department (ED)
      patients has not been identified. Our objective was to determine the diagnostic
      accuracies of electrocardiogram (ECG) and N-terminal Pro-B-type natriuretic
      peptide (pro-BNP) for left ventricular hypertrophy individually and in
      combination in hypertensive ED patients. METHODS: Prospective diagnostic study in
      an academic urban tertiary care hospital ED with annual census of 65,000 visits.
      Inclusion criteria are as follows: adult ED patients with systolic blood pressure
      greater than or equal to 160 mm Hg or diastolic blood pressure greater than or
      equal to 100 mm Hg on 2 or more measurements taken 60 minutes apart. Exclusion
      criteria are as follows: patients with heart failure, renal
      insufficiency/failure, acute myocardial infarction, or without recent or
      scheduled echocardiograms. All patients received echocardiograms and had pro-BNP
      levels measured using a RAMP point-of-care device (Response Biomedical,
      Vancouver, BC, Canada). We calculated diagnostic test characteristics with 95%
      confidence intervals (CIs). RESULTS: A total of 49 patients were enrolled. The
      average age was 57.9 years, 26.5% were male, and 63.3% were African American.
      Thirty-two patients (65%) had left ventricular hypertrophy by echocardiogram.
      Twenty-one (43%) had ECG evidence of left ventricular hypertrophy. Median pro-BNP
      level was 268 pg/mL. The combination of the 2 tests provided the greatest
      specificity (94%; 95% CI, 69%-99.7%) and positive predictive value (94%; 95% CI,
      (68%-99.7%). CONCLUSIONS: The combination of ECG and pro-BNP is a promising
      screening algorithm for identification of hypertensive ED patients with left
      ventricular hypertrophy.

PMID- 21185672
TI  - A patient with foot ulcer and severe metabolic alkalosis.
AB  - We report a case of triple acid-base disorder with metabolic alkalosis as the
      primary disorder in a 65-year-old man due to ingestion and application to leg
      ulcers of baking soda (calcium bicarbonate). The blood pH was 7.65 with
      hypochloremia, hypokalemia, and prerenal azotemia. He was treated with isotonic
      saline with K replacement, and the patient improved without any adverse clinical
      consequences. We discuss the causes, mechanisms, and management of Cl-responsive
      (depletion) metabolic alkalosis.

PMID- 21185673
TI  - Tattoo-induced vasculitis: is it really the ink?

PMID- 21185674
TI  - Clinical triage decision vs risk scores in predicting the need for endotherapy in
      upper gastrointestinal bleeding.
AB  - BACKGROUND: Acute upper gastrointestinal hemorrhage (UGIH) is a common reason for
      hospitalization with substantial associated morbidity, mortality, and cost.
      Differentiation of high- and low-risk patients using established risk scoring
      systems has been advocated. The aim of this study was to determine whether these
      scoring systems are more accurate than an emergency physician's clinical decision
      making in predicting the need for endoscopic intervention in acute UGIH. METHODS:
      Patients presenting to a tertiary care medical center with acute UGIH from 2003
      to 2006 were identified from the hospital database, and their clinical data were
      abstracted. One hundred ninety-five patients met the inclusion criteria and were
      included in the analysis. The clinical Rockall score and Blatchford score (BS)
      were calculated and compared with the clinical triage decision (intensive care
      unit vs non-intensive care unit admission) in predicting the need for endoscopic
      therapy. RESULTS: Clinical Rockall score greater than 0 and BS greater than 0
      were sensitive predictors of the need for endoscopic therapy (95% and 100%) but
      were poorly specific (9% and 4%), with overall accuracies of 41% and 39%. At
      higher score cutoffs, clinical Rockall score greater than 2 and BS greater than 5
      remained sensitive (84% and 87%) and were more specific (29% and 33%), with
      overall accuracies of 48% and 52%. Clinical triage decision, as a surrogate for
      predicting the need for endoscopic therapy, was moderately sensitive (67%) and
      specific (75%), with an overall accuracy (73%) that exceeded both risk scores.
      CONCLUSIONS: The clinical use of risk scoring systems in acute UGIH may not be as
      good as clinical decision making by emergency physicians.

PMID- 21185675
TI  - Venoarterial extracorporeal membrane oxygenation resuscitation in diabetic
      ketoacidosis with hypothermic cardiocirculatory instability.
AB  - Diabetic ketoacidosis with hypothermia is underrecognized, and the mortality rate
      is high at between 30% and 60%. The cause of hypothermia in diabetic ketoacidosis
      patients is speculative and has multiple factors. Insulin deficit is the most
      important factor that leads to a lack of substrate for cellular heat production.
      Water depletion and low environment temperature may also be contributing factors,
      especially in patients with a severe diabetic coma. Hypothermia may also
      aggravate uncontrolled diabetes mellitus and complicate treatment because insulin
      secretion is impaired and exogenous administered insulin is less effective at low
      temperatures. We present a case, the first in the literature, of severe diabetic
      ketoacidosis with marked hypothermia and cardiovascular instability that was
      successfully resuscitated by venoarterial extracorporeal membrane oxygenation
      support. Based on this report, we suggest that portable venoarterial
      extracorporeal membrane oxygenation should be considered to treat patients with
      severe diabetic ketoacidosis and hypothermic cardiocirculatory instability.

PMID- 21185676
TI  - Aluminium-induced ventricular tachycardia.
AB  - Aluminium (Al) is the most widely distributed metal in the environment. It is
      commonly used in daily life, which provides easy exposure to human. The exposure
      to this toxic metal occurs through air, food, and water. The clinical spectrum of
      poisoning varies depending on the dosage and duration of consumption. Acute
      exposure to Al is highly toxic to lungs, heart, and blood vessels causing
      pulmonary edema, shock, and arrhythmias. Chronic exposure to aluminium is
      associated with behavioral, neurologic, and hematologic changes. Some
      epidemiologic studies have shown poor performance in cognitive tests and a higher
      prevalence rate of neurologic symptoms for workers occupationally exposed to
      aluminium. Although there are several reports about ventricular tachycardia in
      case of acute poisoning, there is no report about chronic poisoning. In this
      report, we presented a 20-year-old man who had recurrent ventricular tachycardia.

PMID- 21185677
TI  - Sialolith in a two-year-old.

PMID- 21185678
TI  - A right apical consolidation: images from the emergency department.

PMID- 21185679
TI  - Bilateral loculated pleural effusion as a manifestation of acute parenteral
      organophosphate intoxication: a case report.
AB  - BACKGROUND: Acute organophosphate (OP) toxicity causes a wide range of clinical
      effects on the respiratory system, including pulmonary bronchoconstriction and
      bronchorrhea. Morbidity and mortality from acute OP toxicity correlate best with
      pulmonary secretions. OBJECTIVE: In this article, we report bilateral loculated
      pleural effusion as a rare pulmonary effect in a patient with acute parenteral OP
      toxicity. CASE REPORT: A 25-year-old, previously healthy woman was transferred to
      our Poison Department 3 days after suicidal injection of malathion. At the time
      of presentation her vital signs were normal, except that her respiratory rate was
      24 breaths/min. She complained of pleuritic chest pain and had a cough productive
      of yellow sputum. She had generalized chest wall tenderness, and breath sounds
      were decreased in the base of both lung fields. Standard therapy for OP toxicity,
      including atropine, pralidoxime, and diazepam, was initiated. Due to persistent
      pleuritic chest pain, a computed tomography (CT) scan was performed that showed
      bilateral loculated pleural effusions. Shortly after hospital admission, the
      patient developed respiratory distress, for which she was intubated and
      transferred to the Intensive Care Unit. She received continued medical therapy
      and was extubated on hospital day 3. A CT scan of the chest on hospital day 9,
      after completion of the treatment, documented resolution of the effusions.
      CONCLUSION: Parenteral OP toxicity occurs rarely, and in this case it was
      associated with bilateral loculated pleural effusions. In this regard, it should
      be considered in a patient with acute parenteral OP toxicity and persistent chest
      wall pain.

PMID- 21185680
TI  - Acute handling disturbance modulates plasma insulin-like growth factor binding
      proteins in rainbow trout (Oncorhynchus mykiss).
AB  - The effects of acute stressor exposure on proximal (growth hormone [GH]) and
      distal (insulin-like growth factor-I [IFG-I] and insulin-like growth factor
      binding proteins [IFGBPs]) components of the somatotropic axis are poorly
      understood in finfish. Rainbow trout (Oncorhynchus mykiss) were exposed to a 5
      min handling disturbance to mimic an acute stressor episode, and levels of plasma
      GH, IGF-I, and IGFBPs at 0, 1, 4, and 24 h post-stressor exposure were measured.
      An unstressed group was also sampled at the same clock times (09:00, 10:00,
      13:00, and 08:00 [the following day]) as acute stress sampling to determine
      temporal changes in the above somatotropic axis components. The acute stressor
      transiently elevated plasma cortisol and glucose levels at 1 and 4 h post
      stressor exposure, whereas no changes were seen in the unstressed group. Plasma
      GH levels were not affected by handling stress or sampling time in the unstressed
      animals. Plasma IGF-I levels were significantly depressed at 1 and 4 h post
      stressor exposure, but no discernible temporal pattern was seen in the unstressed
      animals. Using a western ligand blotting technique, we detected plasma IGFBPs of
      21, 32, 42, and 50 kDa in size. The plasma levels of the lower-molecular-weight
      IGFBPs (21 and 32 kDa) were unaffected by handling stressor, nor were there any
      discernible temporal patterns in the unstressed animals. By contrast, the higher
      molecular-weight IGFBPs (42 and 50 kDa) were affected by stress or time of
      sampling. Levels of the 42-kDa IGFBP levels significantly decreased over the
      sampling period in unstressed control animals, but this temporal drop was
      eliminated in stressed animals. Levels of the 50-kDa IGFBPs also decreased
      significantly over the sampling time in unstressed trout, whereas handling
      disturbance transiently increased levels of this IGFBP at 1 h but not at 4 and 24
      h post-stressor exposure compared with the control group. Overall, our results
      suggest that acute stress adaptation involves modulation of plasma IGF-1 and high
      molecular-mass IGFBP levels (42 and 50 kDa) in rainbow trout.

PMID- 21185681
TI  - Effects of orexigenic peptides and leptin on melatonin secretion during different
      photoperiods in seasonal breeding ewes: an in vitro study.
AB  - The pineal gland (PG) acts as a neuroendocrine transducer of daily and seasonal
      time through the nocturnal release of melatonin. Here, we examined the
      interaction of season, orexin, ghrelin, and leptin on melatonin secretion by
      pineal explants in short-term culture. Glands were collected after sunset from 12
      ewes during long days (LD; April and May) and from an additional 12 ewes during
      short days (SD; October and November). Glands were transected sagittally into
      strips, with each equilibrated in 2.5 mL of Dulbecco's modified Eagle's medium
      for 60 min, followed by a 2-h incubation in control medium or medium containing
      orexin B (10 and 100 ng/mL), ghrelin (10 and 100 ng/mL), or 50 ng/mL of leptin.
      After a 3-h incubation, some PG explants treated previously with lower doses of
      orexin or ghrelin were challenged with 50 ng/mL of leptin and those treated with
      both doses of orexin were challenged with 300 nM of the beta-agonist
      isoproterenol. One milliliter of medium was harvested and replaced from each well
      every 30 min. Treatment with the low dose of orexin during LD increased melatonin
      secretion about 110% (P<0.01); treatment with a high dose increased melatonin
      secretion about 47% (P<0.001). During the SD period, leptin stimulated (P < 0.05)
      melatonin secretion slightly compared with mean melatonin concentration in
      controls. However, together, orexin and leptin depressed (P<0.01) melatonin
      secretion. Both doses of ghrelin reduced (P < 0.01) melatonin concentration
      during the SD season compared with control culture. Addition of ghrelin and
      leptin to culture medium increased (P<0.01) melatonin concentration compared with
      ghrelin-treated culture and decreased melatonin concentration (P<0.01) compared
      with leptin-treated culture during SD. Isoproterenol stimulated (P<0.01)
      melatonin secretion compared with values observed during the pretreatment period.
      We conclude that orexigenic peptides (orexin B and ghrelin) and an anorectic
      peptide (leptin) affect PG directly. The responses of PG to those hormones depend
      on day length. Moreover, secretion of melatonin from the ovine PG is under an
      adrenergic regulation.

PMID- 21185682
TI  - Predictors of substance abuse treatment need and receipt among homeless women.
AB  - Many homeless women do not receive needed treatment for substance abuse. This
      study identified social network and other predisposing factors associated with
      perceived need for and receipt of substance abuse treatment among 273 homeless
      women who screened positive for past-year substance abuse. Perceived treatment
      need was more likely among women with drug-using sex partners, a denser network,
      and an arrest history but less likely for those with a minor child and a longer
      history of homelessness. Receiving treatment was more likely among women who
      received informational support from their sex partners and who had an arrest
      history but less likely among those who had a more street-based social network,
      had a minor child, considered themselves homeless, and recently needed mental
      health treatment. Treatment services researchers should attend more closely to
      social contextual factors, as well as the more traditional individual factors, to
      understand access and barriers to treatment.

PMID- 21185683
TI  - Computer-based interventions for drug use disorders: a systematic review.
AB  - A range of innovative computer-based interventions for psychiatric disorders have
      been developed and are promising for drug use disorders due to reduced cost and
      greater availability compared to traditional treatment. Electronic searches were
      conducted from 1966 to November 19, 2009, using MEDLINE, Psychlit, and EMBASE.
      Four hundred sixty-eight nonduplicate records were identified. Two reviewers
      classified abstracts for study inclusion, resulting in 12 studies of moderate
      quality. Eleven studies were pilot or full-scale trials compared to a control
      condition. Interventions showed high acceptability despite substantial variation
      in type and amount of treatment. Compared to treatment-as-usual, computer-based
      interventions led to less substance use and higher motivation to change, better
      retention, and greater knowledge of presented information. Computer-based
      interventions for drug use disorders have the potential to dramatically expand
      and alter the landscape of treatment. Evaluation of Internet- and telephone-based
      delivery that allows for treatment-on-demand in patients' own environment is
      needed.

PMID- 21185684
TI  - Integrated employee assistance program/managed behavioral health plan utilization
      by persons with substance use disorders.
AB  - New federal parity and health reform legislation, promising increased behavioral
      health care access and a focus on prevention, has heightened interest in employee
      assistance programs (EAPs). This study investigated service utilization by
      persons with a primary substance use disorder (SUD) diagnosis in a managed
      behavioral health care (MBHC) organization's integrated EAP/MBHC product (N =
      1,158). In 2004, 25.0% of clients used the EAP first for new treatment episodes.
      After initial EAP utilization, 44.4% received no additional formal services
      through the plan, and 40.4% received regular outpatient services. Overall,
      outpatient care, intensive outpatient/day treatment, and inpatient/residential
      detoxification were most common. About half of the clients had co-occurring
      psychiatric diagnoses. Mental health service utilization was extensive. Findings
      suggest that for service users with primary SUD diagnoses in an integrated
      EAP/MBHC product, the EAP benefit plays a key role at the front end of treatment
      and is often only one component of treatment episodes.

PMID- 21185685
TI  - A brief marijuana intervention for non-treatment-seeking young adult women.
AB  - We randomized 332 women, 18-24 years old, who were not explicitly seeking
      treatment for their marijuana use to either a two-session motivationally focused
      intervention or an assessment-only condition. Assessed by timeline follow-back
      methodology, participants reported using marijuana 57% of days in the 3 months
      prior to study entry. Intervention effects on the likelihood of marijuana use
      were not statistically significant at 1 month (odds ratio [OR] = 0.77, p = .17),
      significant at 3 months (OR = 0.53, p = .01), and no longer significant at 6
      months (OR = 0.74, p = .20). Among the 61% of participants endorsing any desire
      to quit using marijuana at baseline, significant intervention effects on the
      likelihood of marijuana use days were observed at 1 month (OR = 0.42, p = .03), 3
      months (OR = 0.31, p = .02), and 6 months (OR = 0.35, p = .03). A two-session
      brief motivational intervention reduced marijuana use among young women not
      seeking treatment. Women with a desire to quit showed a greater and more durable
      response.

PMID- 21185686
TI  - [Postpartum reversible cerebral angiopathy: an unusual cause of headache].
AB  - We present the case of a 34-year-old woman who developed, in postpartum period of
      an uncomplicated pregnancy, a thunderclap headache with visual disturbance
      associated with a severe arterial hypertension. Both clinical evolution and
      cerebral imaging including angio-MR confirmed the diagnosis of postpartum
      reversible vasoconstriction syndrome. One of the leading causes of this syndrome
      is the use of vasoactive drugs as it was observed in the case of this patient. It
      is important to consider this syndrome in the differential diagnosis in patients
      presenting with headache in the postpartum period.

PMID- 21185687
TI  - [Cerebral haemorrhage: an unusual complication of idiopathic thrombocytopenic
      purpura].

PMID- 21185689
TI  - Quarterly medical review: pulmonary involvement in systemic diseases.

PMID- 21185688
TI  - [Bilateral catheter for continuous TAP block and postoperative pain relief after
      gynecologic surgery].
AB  - We describe the case of two patients who had undergone gynecologic surgery and in
      whom a continuous ropivacaine infusion was administered through a catheter placed
      on each abdominal side, using the technique of ultrasound-guided TAP block.
      Postoperative analgesia was of excellent quality with almost no morphine
      requirement. No side effects were encountered.

PMID- 21185690
TI  - Alternate splint for flexion contracture in children with burns.
AB  - Splinting children and ensuring that children wear the splint can be challenging
      tasks for both the therapist and the caregiver. Sometimes creativity is needed to
      create a pediatric splint that is easy to don and stays in place. These authors
      describe their challenge with pediatric burn patients either not wearing or
      losing their splint and how they now combine the splint directly into the
      pressure garment to ensure better patient compliance

PMID- 21185691
TI  - The presence and impact of stress reactions on disability among patients with arm
      injury.
AB  - This study explores the prevalence and types of stress reactions and their impact
      on self-perceived disability among arm-hand-injured patients. It tested the null
      hypothesis that there is no correlation between stress reactions after traumatic
      hand injury and arm-specific disability. In a prospective cohort of 24 patients,
      stress reactions were measured using the Impact of Events Scale-Revised (IES-R),
      and arm-specific disability was measured using the QuickDASH, an average of 7.5
      months (range: 1.5-33 months) after injury. Type of injury, length of time since
      injury, and gender did not influence scores on the IES-R or the QuickDASH. The
      IES-R subscales of intrusion and hyperarousal correlated with QuickDASH scores
      (intrusion: r=0.57, p=0.004; hyperarousal: r=0.45, p=0.029). These findings
      suggest that the patient may require attention to learn how to engage in the
      therapy process while experiencing stress reactions.

PMID- 21185693
TI  - GRADE guidelines: a new series of articles in the Journal of Clinical
      Epidemiology.
AB  - The "Grades of Recommendation, Assessment, Development, and Evaluation" (GRADE)
      approach provides guidance for rating quality of evidence and grading strength of
      recommendations in health care. It has important implications for those
      summarizing evidence for systematic reviews, health technology assessment, and
      clinical practice guidelines. GRADE provides a systematic and transparent
      framework for clarifying questions, determining the outcomes of interest,
      summarizing the evidence that addresses a question, and moving from the evidence
      to a recommendation or decision. Wide dissemination and use of the GRADE
      approach, with endorsement from more than 50 organizations worldwide, many highly
      influential (http://www.gradeworkinggroup.org/), attests to the importance of
      this work. This article introduces a 20-part series providing guidance for the
      use of GRADE methodology that will appear in the Journal of Clinical
      Epidemiology.

PMID- 21185694
TI  - Clinical application of SPHARM-PDM to quantify temporomandibular joint
      osteoarthritis.
AB  - The severe bone destruction and resorption that can occur in osteoarthritis of
      the temporomandibular joint (TMJ) is associated with significant pain and limited
      joint mobility. However, there is no validated method for the quantification of
      discrete changes in joint morphology in early diagnosis or assessment of disease
      progression or treatment effects. To achieve this, the objective of this cross
      sectional study was to use simulated bone resorption on cone-beam CT (CBCT) to
      study condylar morphological variation in subjects with temporomandibular joint
      (TMJ) osteoarthritis (OA). The first part of this study assessed the hypothesis
      that the agreement between the simulated defects and the shape analysis
      measurements made of these defects would be within 0.5mm (the image's spatial
      resolution). One hundred seventy-nine discrete bony defects measuring 3mm and 6mm
      were simulated on the surfaces of 3D models derived from CBCT images of
      asymptomatic patients using ITK-Snap software. SPHARM shape correspondence was
      used to localize and quantify morphological differences of each resorption model
      with the original asymptomatic control. The size of each simulated defect was
      analyzed and the values obtained compared to the true defect size. The
      statistical analysis revealed very high probabilities that mean shape
      correspondence measured defects within 0.5mm of the true defect size. 95%
      confidence intervals (CI) were (2.67, 2.92) and (5.99, 6.36) and 95% prediction
      intervals (PI) were (2.22, 3.37) and (5.54, 6.82), respectively for 3mm and 6mm
      simulated defects. The second part of this study applied shape correspondence
      methods to a longitudinal sample of TMJ OA patients. The mapped longitudinal
      stages of TMJ OA progression identified morphological variants or subtypes, which
      may explain the heterogeneity of the clinical presentation. This study validated
      shape correspondence as a method to precisely and predictably quantify 3D
      condylar resorption.

PMID- 21185695
TI  - Biodegradable fixation for craniomaxillofacial surgery: a 10-year experience
      involving 761 operations and 745 patients.
AB  - Patient acceptance, safety, and efficacy of poly-l/dl-lactic acid (PLLDL) bone
      plates and screws in craniomaxillofacial surgery are reported in this article.
      Included in the sample are 745 patients who underwent 761 separate operations,
      including more than 1400 surgical procedures (orthognathic surgery (685), bone
      graft reconstruction (37), trauma (191) and transcranial surgery (20)). The
      success (no breakage or inflammation requiring additional operating room
      treatment) was 94%. Failure occurred because of breakage (14) or exuberant
      inflammation (31). All breakage occurred at mandibular sites and the majority of
      inflammatory failure occurred in the maxilla or orbit (29), with only two in the
      mandible. Failures were evenly distributed between the two major vendors. PLLDL
      70/30 bone plates and screws may be used successfully in a variety of
      craniomaxillofacial surgical applications. The advantages include the gradual
      transference of physiological forces to the healing bone, the reduced need for a
      second operation to remove the material and its potential to serve as a vehicle
      to deliver bone-healing proteins to fracture/osteotomy sites. Bone healing was
      noted at all sites, even where exuberant inflammation required a second surgical
      intervention.

PMID- 21185696
TI  - Parental consanguineous marriages and age at onset of schizophrenia.

PMID- 21185697
TI  - Molecular basis of resistance to macrolides, lincosamides and streptogramins in
      Staphylococcus saprophyticus clinical isolates.
AB  - The aim of this study was to evaluate the prevalence of resistance to macrolide
      lincosamide-streptogramin (MLS) antibiotics as well as to assess the molecular
      basis of this resistance amongst 72 Staphylococcus saprophyticus urinary isolates
      collected from 2005 to 2009 in University Hospital of Caen (France). Of the 72
      strains studied, 33 (45.8%) were resistant to at least one MLS antibiotic,
      including 24 (72.7%) with an M phenotype, 5 (15.2%) with an inducible MLS(B)
      phenotype, 3 (9.1%) with a combined M+L phenotype and 1 (3.0%) with an L
      phenotype. All isolates were susceptible to the combination of streptogramins A
      and B. The resistance genes erm(A), erm(B), erm(C), msr(A) and lnu(A) were
      detected alone in 0, 0, 5 (15.2%), 24 (72.7%) and 1 (3.0%) of the 33 MLS
      resistant isolates, respectively, whereas 2 strains (6.1%) were positive for both
      msr(A) and lnu(A). All msr(A)-positive isolates exhibited an M phenotype, whereas
      all five erm(C)-positive and all three lnu(A)-positive strains displayed,
      respectively, an inducible MLS(B) phenotype and an L phenotype with a positive
      Hodge test. Plasmid analysis indicated that erm(C) and lnu(A) genes were borne by
      small-size plasmids (ca. 2.5 kb), whereas larger plasmids (30-90 kb) harboured
      msr(A). In conclusion, these findings show a high prevalence of MLS resistance in
      S. saprophyticus, which was mainly associated with the presence of the msr(A)
      gene. Since S. saprophyticus colonises the gastrointestinal tract, it may
      constitute an unexpected reservoir for MLS resistance genes, in particular
      msr(A), amongst coagulase-negative staphylococci.

PMID- 21185698
TI  - Interpenetrating polymer network (IPN) nanogels based on gelatin and poly(acrylic
      acid) by inverse miniemulsion technique: synthesis and characterization.
AB  - Novel interpenetrating polymer network (IPN) nanogels composed of poly(acrylic
      acid) and gelatin were synthesised by one pot inverse miniemulsion (IME)
      technique. This is based on the concept of nanoreactor and cross-checked from
      template polymerization technique. Acrylic acid (AA) monomer stabilized around
      the gelatin macromolecules in each droplet was polymerized using ammonium
      persulfate (APS) and tetramethyl ethylene diamine (TEMED) in 1:5 molar ratio and
      cross-linked with N,N-methylene bisacrylamide (BIS) to form semi-IPN (sIPN)
      nanogels, which were sequentially cross-linked using glutaraldehyde (Glu) to form
      IPNs. Span 20, an FDA approved surfactant was employed for the formation of
      homopolymer, sIPN and IPN nanogels. Formation of stable gelatin-AA droplets were
      observed at 2% surfactant concentration. Dynamic light scattering (DLS) and
      scanning electron microscopy (SEM) studies of purified nanogels showed small,
      spherical IPN nanogels with an average diameter of 255 nm. In contrast, sIPN
      prepared using the same method gave nanogels of larger size. Fourier-transform
      infrared (FT-IR) spectroscopy, SEM, DLS, X-ray photoelectron spectroscopy (XPS)
      and zeta potential studies confirm the interpenetration of the two networks.
      Leaching of free PAA chains in sIPN upon dialysis against distilled water leads
      to porous nanogels. The non-uniform surface of IPN nanogels seen in transmission
      electron microscopy (TEM) images suggests the phase separation of two polymer
      networks. An increase of N/C ratio from 0.07 to 0.17 (from PAA gel to IPN) and
      O/C ratio from 0.22 to 0.37 (from gelatin gel to IPN) of the nanogels by XPS
      measurements showed that both polymer components at the nanogel surface are
      interpenetrated. These nanogels have tailoring properties in order to use them as
      high potential drug delivery vehicles for cancer targeting.

PMID- 21185699
TI  - A novel biological strategy for morphology control of PbWO4 crystals in tomato
      extract.
AB  - PbWO(4) crystals were readily synthesized by reacting lead oxide (PbO(2)) with
      sodium tungstate (Na(2)WO(4).2H(2)O) at room temperature in the presence of
      tomato extract. Biomolecules such as vitamins, proteins in the extract played
      both the roles of reductant and template. The size and morphology of the PbWO(4)
      crystals could be controlled by adjusting the concentration of the reactants.
      When the concentration ratio of PbO(2) and Na(2)WO(4) was increased, the
      morphologies of the products varied from spherical to fusiform. Room-temperature
      fluorescence spectra indicated the products had a slight blue shift compared to
      the solid structure, which may be due to the structure defects in the crystals.
      The possible mechanism of PbWO(4) crystal growth in tomato extract was discussed.

PMID- 21185700
TI  - Electron arc therapy for bilateral chest wall irradiation: treatment planning and
      dosimetric study.
AB  - AIMS: The treatment of patients with synchronous bilateral breast cancer is a
      challenge. We present a report of dosimetric data of patients with bilateral
      chest walls as the target treated with electron arc therapy. MATERIALS AND
      METHODS: Ten consecutive patients who had undergone electron arc therapy to the
      bilateral chest wall for breast cancer were analysed. After positioning and
      immobilisation, patients underwent computed tomography scans from the neck to the
      upper abdomen. Electron arc plans were generated using the PLATO RTS (V1.8.2
      Nucletron) treatment planning system. Electron energy was chosen depending upon
      the depth and thickness of the planning target volume (PTV). For all patients,
      the arc angle ranged between 80 and 280 degrees  (start angle 80 degrees , stop
      angle 280 degrees ). The homogeneity index, coverage index and doses to organs at
      risk were evaluated. The patient-specific output factor and thermoluminescence
      dosimetry (TLD) measurements were carried out for all patients. The total planned
      dose to the PTV was 50Gy/25 fractions/5 weeks. RESULTS: The mean PTV (+/-
      standard deviation) was 568.9 (+/-116)cm(3). The mean PTV coverage was 89 (+/
      5.8)% of the prescribed dose. For the right lung, the mean values of D(1) and
      D(10) were 46 (+/-7.6) and 30 (+/-9)Gy, respectively. For the left lung, the mean
      values of D(1) and D(10) were 45 (+/-7) and 27 (+/-8)Gy, respectively. For the
      heart, the mean values of D(1), D(5) and D(10) were 21 (+/-15), 13.5 (+/-12) and
      9 (+/-9)Gy, respectively. The mean values of TLD at various pre-specified
      locations on the chest wall surface were 1.84, 1.82, 1.82, 1.89 and 1.78Gy,
      respectively CONCLUSION: The electron arc technique for treating the bilateral
      chest wall is a feasible and pragmatic technique. This technique has the twin
      advantages of adequate coverage of the target volume and sparing of adjacent
      normal structures. However, compared with other techniques, it needs a firm
      quality assurance protocol for dosimetry and treatment delivery.

PMID- 21185701
TI  - MAT1A variants modulate the effect of dietary fatty acids on plasma homocysteine
      concentrations.
AB  - BACKGROUND AND AIM: Dietary n-3 polyunsaturated fatty acids (PUFAs) are
      associated with decreased plasma homocysteine (Hcy), an important biomarker for
      cardiovascular disease. The S-adenosylmethionine synthetase type-1 (MAT1A), an
      essential enzyme in the conversion of methionine to S-adenosylmethionine, plays a
      key role in homocysteine metabolism. This study investigated the interaction
      between dietary fatty acids and MAT1A genotypes on plasma Hcy concentrations
      among Boston Puerto Ricans. METHODS AND RESULTS: Plasma Hcy and MAT1A genotypes
      were determined in 994 subjects of the Boston Puerto Rican Health Study. Dietary
      fatty acid intakes were assessed by interviews using a questionnaire adapted from
      the NCI/Block food frequency form. RESULT: In the cross-sectional analysis,
      genetic variant MAT1A 3U1510 displayed a significant interaction with dietary n
      3:n-6 PUFA ratio in determining plasma Hcy (p-value for interaction = 0.025).
      3U1510G homozygotes had significantly lower plasma Hcy concentration than major
      allele homozygotes and heterozygotes (AA + AG) (p-value for trend = 0.019) when
      the n-3:n-6 ratio was >0.09. Two other MAT1A variants, d18777 and i15752, also
      showed significant interactions with different constituents of dietary fat
      influencing Hcy concentrations. Furthermore, haplotypes consisting of three
      variants displayed a strong interaction with n3:n6 ratio influencing Hcy
      concentrations. CONCLUSIONS: Our results suggest that MAT1A genotypes appear to
      modulate effects of dietary fat on plasma Hcy.

PMID- 21185702
TI  - Association between the rs1050450 glutathione peroxidase-1 (C > T) gene variant
      and peripheral neuropathy in two independent samples of subjects with diabetes
      mellitus.
AB  - Glutathione peroxidase-1 (GPx-1) is an endogenous anti-oxidant enzyme. The T
      allele of the GPx-1 rs1050450 (C > T) gene variant is associated with reduced
      enzyme activity. Our aim was to examine the association between this gene variant
      and peripheral neuropathy in two cross-sectional samples of subjects with
      diabetes: (i) 773 Caucasian subjects were genotyped from the UCL Diabetes and
      Cardiovascular disease Study (UDACS) and (ii) 382 Caucasian subjects from the
      Ealing Diabetes Study (EDS). Peripheral neuropathy status (and oxidised-LDL [Ox
      LDL:LDL] and plasma Total Ant-ioxidant Status [TAOS] in UDACS), were analysed in
      relation to genotype. We observed that: (i) In UDACS, the odds ratio (OR) for
      peripheral neuropathy in the T allele carriers compared to the CC genotype was
      1.61 [1.10-2.28], p = 0.01. This remained significant after adjustment for other
      risk factors. Ox-LDL:LDL ratio was significantly elevated in T allele carriers
      (CC vs. CT/TT: 16.3 +/- 2.4 v 18.0 +/- 2.9 U/mmol LDL, p = 0.02). (ii) In EDS,
      the OR for peripheral neuropathy in the T allele carriers compared to the CC
      genotype was 1.95 [1.11-3.42], p = 0.02. This remained significant after
      adjustment for other risk factors. In conclusion, we observed a significant
      association between the T allele and peripheral neuropathy and LDL oxidation.
      This is the first paper to examine the rs1050450 variant in two samples of
      Caucasian subjects with diabetes. Prospective analysis of the gene variant is
      required in diabetic and healthy cohorts with measured plasma markers of
      oxidative stress to investigate the described association further.

PMID- 21185703
TI  - Genetic and environmental relationships between Framingham Risk Score and
      adiposity measures in Koreans: the Healthy Twin study.
AB  - BACKGROUND AND AIMS: We examined heritability and bivariate analyses for the
      Framingham Risk Score (FRS) and adiposity measures among Koreans. METHODS AND
      RESULTS: We analysed the data from 2496 participants (962 men, 1534 women, age 30
      74 years), including 1320 non-twin family members, 468 monozygotic (MZ) and 120
      dizygotic (DZ) twin pairs, collected from the Healthy Twin study of Korea.
      Adiposity measurements comprised BMI, waist circumference (WC), waist-to-hip
      ratio and waist-to-height ratio (WHTR). Analyses were conducted using the
      Sequential Oligogenic Linkage Analysis Routines (SOLAR) package software. The co
      twin control analyses shows that estimates of within-pair regression coefficients
      in the relationship between adiposity traits and FRS were attenuated for MZ twin
      pairs, relative to DZ twin pairs (0.11-0.26 vs. 0.60-0.71). The heritability
      estimate for FRS was 0.37, and the estimates for adiposity traits ranged from
      0.45 to 0.63 (P < 0.001). Bivariate analysis revealed genetic correlations
      between FRS, and all of the adiposity traits ranged from 0.16 (for WHTR, P >
      0.05) to 0.46 (for WC, P < 0.001). The common environmental correlations between
      FRS and each of the adiposity traits ranged from 0.43 to 0.66 (P < 0.001).
      CONCLUSIONS: FRS and each of the obesity traits shared common genetic and
      environmental relationships. These findings support a pleiotropic action between
      genes associated with adiposity traits and FRS and a need of further
      investigations for identifying specific common environmental factors.

PMID- 21185704
TI  - Piscivorous cyprinid fish modulates suction feeding kinematics to capture elusive
      prey.
AB  - Previous studies have shown that evasive prey generally elicit a different
      kinematical pattern of prey capture from suction feeding fish compared to non
      evasive types of prey. However, no evidence exists that predatory fish can
      modulate their prey capture kinematics in response to whether or not an elusive
      prey performs an escape response. Here, we analyse prey capture kinematics of a
      specialist piscivore (asp, Aspius aspius) during feeding on untethered, live
      goldfish, which regularly displayed escape attempts when attacked by the asp.
      Significant modulation occurred in function of the escape attempts of prey: mouth
      opening was prolonged and increased in magnitude, and one individual also showed
      an increased hyoid depression when feeding on prey trying to escape. As the
      orientation of the prey with respect to the predator prior to the start of mouth
      opening was related to the probability of observing an escape attempt, asp could
      theoretically perform this type of modulation by a priori choosing a pre
      programmed motor pattern. However, since contact between the prey and the asp's
      mouth appeared to be a factor improving the timing of mouth closing, this fine
      tuning of prey capture kinematics is more likely to be caused by reflexive neural
      feedback control.

PMID- 21185707
TI  - Editorial overview.

PMID- 21185705
TI  - Molecular profiling to identify relevant immune resistance mechanisms in the
      tumor microenvironment.
AB  - The molecular identification of tumor antigens initially catalyzed substantial
      enthusiasm for the development of tumor antigen-based vaccines for the treatment
      of cancer. However, numerous vaccine approaches in melanoma and other cancers
      have yielded a low rate of clinical response, despite frequent induction of
      specific T cells as detected in the peripheral blood. This observation has
      prompted several investigators to begin interrogating the tumor microenvironment
      for biologic correlates to tumor response versus resistance. Evidence is
      beginning to emerge suggesting that distinct subsets of tumors may exist that
      reflect distinct categories of immune escape. Lack of chemokine-mediated
      trafficking, poor innate immune cell activation, and the presence of specific
      immune suppressive mechanisms can be found to characterize subsets of tumors. A
      non-inflamed tumor phenotype may predict for resistance to cancer vaccines,
      suggesting a possible predictive biomarker and patient enrichment strategy. But
      in addition, characterization of these subsets may pave the way for catering
      therapeutic interventions toward the biologic features of the tumor in individual
      patients.

PMID- 21185706
TI  - Prevention of cancer by prophylactic human papillomavirus vaccines.
AB  - Oncogenic human papillomaviruses (HPVs) are exclusively mucosal pathogens that
      are noncytopathic and the basal epithelial cells harboring and maintaining an
      infection do not produce either capsid antigen or virus. The efficacy of the
      licensed L1 virus-like particle (VLP) vaccines has encouraged development of
      several second generation vaccines aimed at expanding the coverage to all
      oncogenic HPV types and reducing barriers to global implementation. Currently
      there is no defined immune correlate of protection that can be used to determine
      if an individual patient is protected and for the evaluation of these second
      generation vaccines. Surprisingly, passive transfer of neutralizing serum
      antibody is protective in animal models. Recent studies suggest how neutralizing
      antibody mediates immunity against mucosal HPV and the possible impact of memory
      B cells.

PMID- 21185708
TI  - Docosahexaenoic acid reverts resistance to UV-induced apoptosis in human
      keratinocytes: involvement of COX-2 and HuR.
AB  - The dramatic increase in the incidence of nonmelanoma skin cancer over the last
      decades has been related to the augmented exposure to ultraviolet (UV) radiation
      (UVR). It is known that apoptosis is induced as a protective mechanism after the
      acute irradiation of keratinocytes, whereas apoptotic resistance and
      carcinogenesis may follow the chronic exposure to UVR. We found that not all the
      human keratinocytes lines studied underwent apoptosis following acute exposure to
      UVR (10-60 mJ/cm(2)). Whereas UVR induced apoptosis in the HaCaT cells, NCTC 2544
      and nr-HaCaT cells showed apoptosis resistance. The cytokeratin pattern of the
      apoptosis-resistant cells indicated that they possessed a degree of
      differentiation lower than that of HaCaT cells. They also showed an enhanced
      expression of cyclooxygenase-2 (COX-2), an early marker of carcinogenesis in
      various tissues, including skin. n-3 polyunsaturated fatty acids have drawn
      increasing interest as nutritional factors with the potential to reduce UVR
      carcinogenesis, and since they are apoptosis inducers and COX-2 inhibitors in
      cancer cells, we investigated the ability of n-3 polyunsaturated fatty acids to
      influence the resistance to UVR-induced apoptosis in keratinocytes. We observed
      that docosahexaenoic acid (DHA) reverted the resistance of nr-HaCaT cells to UVR
      induced apoptosis, increasing the Bax/Bcl-2 ratio and caspase-3 activity, and
      reduced COX-2 levels by inhibiting the expression of the human antigen R (HuR), a
      known COX-2 mRNA stabilizer in keratinocytes. The transfection of nr-HaCaT cells
      with HuR siRNA mimicked the proapoptotic effect of DHA. Overall, our findings
      further support the role of DHA as a suitable anticarcinogenic factor against
      nonmelanoma skin cancers.

PMID- 21185709
TI  - Protection and reversal of hepatic fibrosis by red wine polyphenols in
      hyperhomocysteinemic mice.
AB  - Hyperhomocysteinemia leads to several clinical manifestations and, particularly,
      liver disease. Lowering homocysteine through nutrition or other means might offer
      preventive or therapeutic benefits. Polyphenols are natural compounds known for
      their antioxidant and healing properties for vessels. In a previous study we have
      shown a beneficial effect of a red wine polyphenolic extract (PE) administration
      on plasma homocysteine level in cystathionine beta synthase deficient mice, a
      murine model of hyperhomocysteinemia. These mice also develop hepatic fibrosis.
      As increased matrix metalloproteinase (MMP) 2 has been shown to be involved in
      the development of hepatic fibrosis, we then focused on the effect of PE
      administration on expression and activity of MMP-2 in liver of
      hyperhomocysteinemic mice and its impact on hepatic fibrosis development. PE was
      added for four weeks to the drinking water of heterozygous cystathionine beta
      synthase-deficient mice fed a high-methionine diet. Effects of PE administration
      were examined by histological analysis with Sirius red staining, zymography,
      immunobloting, real-time quantitative reverse transcriptase polymerase chain
      reaction, peroxynitrite level, catalase activity and nicotinamide adenine
      dinucleotide phosphate oxidase activity. We show that administration of PE had a
      beneficial effect (i) on MMP-2 expression via modulation of nitrotyrosine
      modified total protein level and (ii) on MMP-2 activity via modulation of its
      activator/inhibitor balance. We also demonstrated a reversal effect of PE
      supplementation on hepatic fibrosis development. Our results demonstrate a
      preventive action of PE administration on biomarkers of hepatic dysfunction due
      to hyperhomocysteinemia.

PMID- 21185710
TI  - Availability and properties of materials for the Fakse Landfill biocover.
AB  - Methane produced in landfills can be oxidized in landfill covers made of compost;
      often called biocovers. Compost materials originating from seven different
      sources were characterized to determine their methane-oxidizing capacity and
      suitability for use in a full-scale biocover at Fakse Landfill in Denmark.
      Methane oxidation rates were determined in batch incubations. Based on material
      availability, characteristics, and the results of batch incubations, five of the
      seven materials were selected for further testing in column incubations. Three of
      the best performing materials showed comparable average methane oxidation rates:
      screened garden waste compost, sewage sludge compost, and an unscreened 4-year
      old garden waste compost (120, 112, and 108 gm(-2)d(-1), respectively). On the
      basis of these results, material availability and cost, the unscreened garden
      waste compost was determined to be the optimal material for the biocover.
      Comparing the results to criteria given in the literature it was found that the
      C/N ratio was the best indicator of the methane oxidation capacity of compost
      materials. The results of this work indicate that batch incubations measuring
      methane oxidation rates offer a low-cost and effective method for comparing
      compost sources for suitability of use in landfill biocovers.

PMID- 21185711
TI  - Ultra-sensitive biosensor based on mesocellular silica foam for organophosphorous
      pesticide detection.
AB  - A sensitive amperometric acetylcholinesterase (AChE) biosensor was fabricated
      based on mesocellular silica foam (MSF), which functioned as both an enzyme
      immobilization matrix and a solid phase extraction (SPE) material for the
      preconcentration of target molecules. The hydrophilic interface, the good
      mechanical/chemical stability, and the suitable pore dimension of MSF provided
      the entrapped AChE a good environment to well maintain its bioactivity at basic
      condition. The AChE immobilized in MSF showed improved catalytic ability for the
      hydrolysis of acetylthiocholine, as evidenced by the increasing of the oxidation
      current of thiocholine, the enzymatic catalytic hydrolysis production of
      acetylthiocholine. In addition, the MSF with large surface area showed a modest
      adsorption capacity for monocrotophos, a model organophosphate used in this
      study, via the hydrogen bond or physical adsorption interaction. The combination
      of the SPE and the good enzyme immobilization ability in MSF significantly
      promoted the sensitivity of the biosensor, and the limit of detection has lowered
      to 0.05 ng/mL. The biosensor exhibited accuracy, good reproducibility, and
      acceptable stability when used for garlic samples analysis. The strategy may
      provide a new method to fabricate highly sensitive biosensors for the detection
      of ultra-trace organophosphorous pesticide infield.

PMID- 21185713
TI  - Monitoring of dopamine release in single cell using ultrasensitive ITO
      microsensors modified with carbon nanotubes.
AB  - The study of single cell dynamics has been greatly adapted in biological and
      medical research and applications. In this work a novel microfluidic
      electrochemical sensor with carbon nanotubes (CNTs) modified indium tin oxide
      (ITO) microelectrode was developed for single cells release monitoring. The
      sensitivity of the electrochemical sensor after CNTs surface modification was
      improved by 2.5-3 orders of magnitude. The developed CNTs modified ITO sensor was
      successfully employed to monitor the dopamine release from single living rat
      pheochromocytoma (PC 12) cells. Its ultrahigh sensitivity, transparency and need
      for fewer agents enable this smart electrochemical sensor to become a powerful
      tool in recording dynamic release from various living tissues and organs
      optically and electrically.

PMID- 21185712
TI  - Facile synthesis of Fe(3)O(4)@Al(2)O(3) core-shell nanoparticles and their
      application to the highly specific capture of heme proteins for direct
      electrochemistry.
AB  - In this study, magnetic core-shell Fe(3)O(4)@Al(2)O(3) nanoparticles (NPs)
      attached to the surface of a magnetic glassy carbon electrode (MGCE) were used as
      a functional interface to immobilize several heme proteins including hemoglobin
      (Hb), myoglobin (Mb) and horseradish peroxidase (HRP) for fabricating
      protein/Fe(3)O(4)@Al(2)O(3) film. Transmission electron microscope, UV-vis
      spectroscopy, electrochemical impedance spectroscopy, and cyclic voltammetry were
      used to characterize the films. With the advantages of the magnetism and the
      excellent biocompatibility of the Fe(3)O(4)@Al(2)O(3) NPs, the
      protein/Fe(3)O(4)@Al(2)O(3) film could be easily fabricated in the present of
      external magnetic field, and well retained the bioactivity of the immobilized
      proteins, hence dramatically facilitated direct electron transfer of heme
      proteins and excellent electrocatalytic behaviors towards H(2)O(2) were
      demonstrated. The presented system avoids the complex synthesis for protecting
      Fe(3)O(4) NPs, supplies a facile, low cost and universal way to immobilize
      proteins, and is promising for construction of third-generation biosensors and
      other bio-magnetic induction devices.

PMID- 21185714
TI  - Three-step electrodeposition synthesis of self-doped polyaniline nanofiber
      supported flower-like Au microspheres for high-performance biosensing of DNA
      hybridization recognition.
AB  - A three-step electrodeposition method has been successfully adopted to fabricate
      morphology-controlled novel Au microspheres on self-doped polyaniline nanofibers
      (nanoSPAN) modified glassy carbon electrode. The deposition conditions, such as
      HAuCl(4) concentration and deposition step, have significant influences on the
      morphologies and electrochemical properties of the resulted Au microspheres. Well
      hierarchical and homogeneously dispersed flower-like Au microspheres (HHFAu) were
      obtained under optimal conditions by the three-step electrodeposition strategy in
      5.0mM HAuCl(4) solution. HHFAu possess large surface area, excellent electron
      transfer ability and good biocompatibility. The DNA probe could be effectively
      attached to HHFAu and thus a high-performance DNA biosensor was constructed by
      using electrochemical impedance spectroscopy as detection method. A gene fragment
      of the cauliflower mosaic virus 35S gene, which is related to one of the
      screening genes for the transgenically modified plants, has been satisfactorily
      detected. The linear range was from 1.0 * 10(-13)M to 1.0 * 10(-6)M and the
      detection limit was 1.9 * 10(-14)M. This HHFAu/nanoSPAN-based impedance
      biosensing platform holds great promise for the detection of other biological and
      chemical molecules.

PMID- 21185715
TI  - Molecular electronics based nanosensors on a viral scaffold.
AB  - Assembling and interconnecting the building blocks of nanoscale devices and being
      able to electronically address or measure responses at the molecular level
      remains an important challenge for nanotechnology. Here we show the usefulness of
      bottom-up self-assembly for building electronic nanosensors from multiple
      components that have been designed to interact in a controlled manner. Cowpea
      mosaic virus was used as a scaffold to control the positions of gold
      nanoparticles. The nanoparticles were then interconnected using thiol-terminated
      conjugated organic molecules, resulting in a three-dimensional conductive
      network. Biotin molecules were attached to the virus scaffold using linkers to
      act as molecular receptors. We demonstrated that binding avidin to the biotin
      receptors on the self-assembled nanosensors causes a significant change in the
      network conductance that is dependent on the charge of the avidin protein.

PMID- 21185716
TI  - Use of a novel micro-fluidic device to create arrays for multiplex analysis of
      large and small molecular weight compounds by surface plasmon resonance.
AB  - There is an increasing demand to develop biosensor monitoring devices capable of
      biomarker profiling for predicting animal adulteration and detecting multiple
      chemical contaminants or toxins in food produce. Surface plasmon resonance (SPR)
      biosensors are label free detection systems that monitor the binding of specific
      biomolecular recognition elements with binding partners. Essential to this
      technology are the production of biochips where a selected binding partner,
      antibody, biomarker protein or low molecular weight contaminant, is immobilised.
      A micro-fluidic immobilisation device allowing the covalent attachment of up to
      16 binding partners in a linear array on a single surface has been developed for
      compatibility with a prototype multiplex SPR analyser. The immobilisation unit
      and multiplex SPR analyser were respectively evaluated in their ability to be fit
      for-purpose for binding partner attachment and detection of high and low
      molecular weight molecules. The multiplexing capability of the dual technology
      was assessed using phycotoxin concentration analysis as a model system. The
      parent compounds of four toxin groups were immobilised within a single chip
      format and calibration curves were achieved. The chip design and SPR technology
      allowed the compartmentalisation of the binding interactions for each toxin group
      offering the added benefit of being able to distinguish between toxin families
      and perform concentration analysis. This model is particularly contemporary with
      the current drive to replace biological methods for phycotoxin screening.

PMID- 21185717
TI  - Progress in Arabidopsis starch research and potential biotechnological
      applications.
AB  - For the past decade, Arabidopsis has been the model higher plant of choice.
      Research into leaf starch metabolism has demonstrated that Arabidopsis is a
      useful system in which to make fundamental discoveries about both starch
      biosynthesis and starch degradation. This review describes recent discoveries in
      these fields and illustrates how such discoveries might be applied in the green
      biotechnology sector to improve and diversify our starch crops.

PMID- 21185718
TI  - Structural insight on processivity, human disease and antiviral drug toxicity.
AB  - DNA polymerase gamma (Pol gamma) is a nuclear encoded, mitochondrially located
      replicase that conducts all DNA synthesis in the organelle. Structurally, human
      Pol gamma closely resembles bacteriophage T7 DNA polymerase. Perhaps due to this
      prokaryotic-like feature, Pol gamma is highly susceptible to inhibition by drugs
      designed against HIV reverse transcriptase and HCV RNA polymerase. In this
      review, I summarize recent structural and biochemical studies towards
      understanding Pol gamma-mediated antiviral drug toxicity.

PMID- 21185719
TI  - Herbal therapy use by cancer patients: a literature review on case reports.
AB  - Complementary and alternative medicine use is common amongst cancer patients. In
      many surveys, herbal medicines are amongst the most commonly used group of
      treatments. Herbal remedies are believed by the general public to be safe, cause
      less side-effects and less likely to cause dependency. The authors performed a
      literature review to assess which herbal approaches have had associated cancer
      case reports and determine which of these have been studied in prospective
      research. Eighteen case reports of patients having apparent antitumour effects
      from herbal therapy and 21 case reports of toxic effects of herbs used by cancer
      patients were identified. Clinicaltrials.gov and MEDLINE (via PubMed) were
      searched for each of the herbal products identified in these reports. Clinical
      trials in cancer populations were identified for green tea extracts or compounds
      (n=34), phytoestrogens (n=27), mistletoe (n=8), Ganoderma lucidum (n=1), noni
      (n=1) and Silymarin (n=1). Daikenchuto, PC-SPES, Nyoshinsan/TJ and Saw palmetto
      have also been studied prospectively. In conclusion, some of the herbs with
      promising case report findings have undergone prospective clinical investigations
      but many others have either not yet been explored or the results have not been
      reported in English. Unconventional therapies, such as herbs and minerals, used
      in ancient medical traditions have led to the identification of active anticancer
      agents. Mechanisms to support prospective research with such approaches are
      discussed.

PMID- 21185720
TI  - Abundance of amoA genes of ammonia-oxidizing archaea and bacteria in activated
      sludge of full-scale wastewater treatment plants.
AB  - In this study, the abundance and sequences of amoA genes of ammonia-oxidizing
      archaea (AOA) and bacteria (AOB) were determined in seven wastewater treatment
      plants (WWTPs) whose ammonium concentrations in influent and effluent wastewaters
      varied considerably (5.6-422.3 mgN l(-1) and 0.2-29.2 mgN l(-1), respectively).
      Quantitative real-time PCR showed that the comparative abundance of AOA and AOB
      amoA genes differed among the WWTPs. In all three industrial WWTPs, where the
      influent and effluent contained the higher levels of ammonium (36.1-422.3 mgN l(
      1) and 5.3-29.2 mgN l(-1), respectively), more than four orders of magnitude
      higher numbers of AOB amoA genes than AOA amoA genes arose (with less than the
      limit of detection of AOA amoA genes). In contrast, significant numbers of AOA
      amoA genes occurred in all municipal WWTPs (with ammonium levels in the influent
      and effluent of 5.6-11.0 mgN l(-1) and 0.2-3.0 mgN l(-1), respectively).
      Statistical analysis suggested that compared to other plants' parameters, the
      ammonium levels in the plants' effluent showed correlation with the highest p
      value to the abundance of AOA amoA genes.

PMID- 21185721
TI  - Potent and selective thiophene urea-templated inhibitors of S6K.
AB  - S6K1 (p70 S6 kinase-1) is thought to play a critical role in the development of
      obesity and insulin resistance, thus making it an attractive target in developing
      medicines for the treatment of these disorders. We describe a novel thiophene
      urea class of S6K inhibitors. The lead matter for the development of these
      inhibitors came from mining the literature for reports of weak off-target S6K
      activity. These optimized inhibitors exhibit good potency and excellent
      selectivity for S6K over a panel of 43 kinases.

PMID- 21185722
TI  - Azaindoles as potent CRTH2 receptor antagonists.
AB  - A new class of 7-azaindole analogs of MK-7246 as potent and selective CRTH2
      antagonists is reported. The SAR leading to the identification of the optimal
      azaindole regioisomer as well as the pharmacokinetics and off-target activities
      of the most potent antagonists are disclosed.

PMID- 21185723
TI  - Descriptive epidemiology of breast cancer in Vojvodina.
AB  - The main aim of our study was to perform the epidemiological analysis of the
      breast cancer in Autonomous Province of Vojvodina, Republic of Serbia, in 15
      years period (1987-2001). Descriptive method was used in epidemiological analysis
      of the data from the Vojvodina cancer registry. According to our results the
      breast cancer is the most frequent neoplasm in women in Vojvodina (26.54% of all
      cancers), and the leading cause of mortality (20.97%). Linear trend for both
      incidence and mortality crude and standardized rates showed the significant and
      unfavorable increase from 1987 to 2001.

PMID- 21185724
TI  - Tamoxifen, cytochrome P450 genes and breast cancer clinical outcomes.
AB  - Tamoxifen has a key role in the management of women with hormone receptor (HR)
      positive breast cancer. It is the endocrine treatment of choice in premenopausal
      women with HR positive breast cancer and is also clinically indicated in
      significant numbers of post-menopausal women who have relative contraindications
      to aromatase inhibitors. Tamoxifen is a pro-drug that is metabolised to its
      active metabolites by the cytochrome P450 (CYP) enzymes including CYP2D6, CYP3A,
      CYP2B6, and CYP2C19. The CYP genes are polymorphic resulting in variable enzyme
      activity. Retrospective clinical data suggests that specific single nucleotide
      polymorphisms (SNPs) of CYP2D6 can lead to null or reduced enzyme activity
      resulting in worse outcomes for those individuals when treated with tamoxifen for
      HR positive breast cancer. There is however a lack of robust prospective clinical
      data on this subject. Commercial tests are now available for the genotyping of
      CYP2D6 with the aim of individualisation of tamoxifen therapy for patients with
      HR positive breast cancer. Selective serotonin reuptake inhibitor antidepressant
      drugs such as paroxetine and fluoxetine have also been used to manage tamoxifen
      induced hot flushes. These drugs potently inhibit the metabolism of tamoxifen by
      CYP2D6 and thus potentially may lessen the efficacy of tamoxifen. The genetic
      variations in other enzymes involved in tamoxifen metabolism (CYP3A, CYP2B6,
      CYP2C19) do not appear to cause any meaningful difference in the efficacy of
      tamoxifen. This review article will summarize the available published breast
      cancer data on the interaction between the relevant SNPs for CYP2D6, CYP3A,
      CYP2B6, and CYP2C19 and the efficacy of tamoxifen, their role in
      individualisation of hormonal therapy and the role of the commercially available
      genotyping kits.

PMID- 21185725
TI  - Immediate effects of therapeutic music on loaded sit-to-stand movement in
      children with spastic diplegia.
AB  - The effects of patterned sensory enhancement (PSE) music on muscle power and
      movement control in children with spastic diplegia (SD) during loaded sit-to
      stand (LSTS) were investigated. Twenty-three children with SD aged 5 to 12 years
      were recruited. Individualized PSE was composed by a music therapist based on
      each subject's sit-to-stand (STS) movement with 50% 1-repetition maximum load.
      Each subject performed LSTS continuously for eight repetitions under randomly
      assigned music or no-music (Control) conditions while the kinematic and kinetic
      data were measured simultaneously. For the music condition, PSE music was played
      only during the first five repetitions (PSE condition), and the following three
      repetitions were referred to as the Continuation condition. Paired t- or Wilcoxon
      signed rank tests were used to compare the variables between the PSE and Control
      conditions, and between the Continuation and Control conditions. Compared to the
      Control condition, greater peak knee extensor power (P=0.009), greater total
      extensor power (P=0.015), and better center-of-mass smoothness (P=0.01), but less
      movement time (P=0.003) were found in the PSE condition. Significant effects of
      the PSE music on the above variables were also found for Continuation condition.
      The current results showed that individualized PSE music helped improve the
      performance of LSTS in children with SD. The associated biomechanical features
      also continued to exist in subsequent movement cycles after the music had ceased.
      These findings suggest that therapy using LSTS combined with PSE music may be
      beneficial for rehabilitating children with SD.

PMID- 21185726
TI  - Association between isometric muscle strength and gait joint kinetics in
      adolescents and young adults with cerebral palsy.
AB  - The purpose of this study was to determine the association between isometric
      muscle strength of the lower limbs and gait joint kinetics in adolescents and
      young adults with cerebral palsy (CP). Twenty-five participants (11 males) with
      bilateral spastic CP, aged 14-22 years (mean: 18.9, sd: 2.0 yr) and Gross Motor
      Function Classification System (GMFCS) level II (n=19) and III (n=6) were tested.
      Hand held dynamometry was used to measure isometric strength (expressed in Nm/kg)
      of the hip, knee, and ankle muscles using standardized testing positions and
      procedures. 3D gait analysis was performed with a VICON system to calculate joint
      kinetics in the hip, knee and ankle during gait. Ankle peak moments exceeded by
      far the levels of isometric strength of the plantar flexors, while the knee and
      hip peak moments were just at or below maximal isometric strength of knee and hip
      muscles. Isometric muscle strength showed weak to moderate correlations with peak
      ankle and hip extension moment and power during walking. Despite considerable
      muscle weakness, joint moment curves were similar to norm values. Results suggest
      that passive stretch of the muscle-tendon complex of the triceps surae
      contributes to the ankle moment during walking and that muscle strength
      assessment may provide additional information to gait kinetics.

PMID- 21185727
TI  - A prospective study of surgical patterns of care for high grade glioma in the
      current era of multimodality therapy.
AB  - Previous surgical patterns of care reports in high grade glioma (HGG) antedated
      the use of chemo-radiotherapy. This study, from an elective neurosurgical centre
      serving an isolated population of over 2 million, identified adult patients with
      HGG from a prospective multidisciplinary database. Of 328 patients in Western
      Australia who were diagnosed with HGG between 1 June 2006 and 30 June 2008, 283
      patients (86%) received care at the study site. A total of 4% were diagnosed on
      imaging and clinical factors alone; 12% had surgery outside the study site. The
      remaining 231 patients had 264 surgical procedures; 78% resection and 22% biopsy.
      Median survival (grade IV) was 9.4 months. Resection predicted improved survival
      (hazard ratio 0.64; 95% confidence interval 0.4-0.89); however, in multivariable
      analysis, only age and grade predicted outcome. The proportion of patients having
      no tissue diagnosis, or biopsy alone, compares favourably with data before the
      use of chemo-radiotherapy, as does survival. The therapeutic nihilism surrounding
      HGG may have decreased since the introduction of temozolomide.

PMID- 21185728
TI  - Clinical characteristics and therapeutic outcome of Gram-negative bacterial
      spinal epidural abscess in adults.
AB  - Gram-negative (G(-)) bacterial spinal epidural abscess (SEA) in adults is
      uncommon. Of the 42 adult patients with bacterial SEA admitted to the Chang Gung
      Memorial Hospital - Kaohsiung, between 2003 and 2007, 12 with G(-) SEA were
      included in this study. Of these 12 patients, seven were men and five were women;
      their ages ranged between 17 years and 81 years (median=72.5 years, mean=62.5
      years). The patients were admitted at different stages of symptom onset (four
      were in the acute stage and four each in the subacute and chronic stages) and at
      different levels of neurologic deficit severity, ranging from back pain to
      paraplegia. Of these 12 patients, 11 had a medical and/or neurosurgical condition
      as the preceding event and four had a concomitant infection at other sites. Back
      pain (83%, 10/12) was the most common clinical presentation, followed by
      paraparesis (50%, 6/12), radiating pain (33%, 4/12), and urinary retention (25%,
      3/12). The following causative G(-) pathogens were detected: Klebsiella
      pneumoniae (three patients), Salmonella spp. (three), Escherichia coli (two),
      Enterobacter spp. (two), Aeromonas hydrophila (one), and Prevotella
      melaninogenica (one). Both Enterobacter strains were resistant to multiple
      antibiotics. Of the 12 patients, eight (66.7%) had spontaneous SEA, whereas the
      remaining four had postneurosurgical SEA. Thoracic, lumbar, and thoracolumbar
      spine segments were the most commonly affected. After receiving medical and/or
      surgical treatment, 10 of the 12 patients (83%) survived, and all 10 recovered
      well. In conclusion, G(-) bacterial SEA accounted for 28.5% (12/42) of adult SEA.
      The causative G(-) pathogens found in this study were different from those
      reported in Western countries, and the strains noted in our study had multiple
      antibiotic resistance. Our findings suggest that the choice of initial empirical
      antibiotics for SEA should be carefully considered.

PMID- 21185729
TI  - Analysis of Revision Anterior Cruciate Ligament Reconstruction according to the
      combined injury, degenerative change, and MRI findings.
AB  - The purposes of this study were to analyze the results of revision ACL
      reconstruction, and to determine the effects of pre-revision combined injuries,
      degenerative changes, and post-revision magnetic resonance imaging (MRI) findings
      on clinical results. Forty patients (41 operations) were enrolled in this study.
      Clinical results and stabilities were evaluated. Radiological results were
      evaluated using Fairbank scale. For the subgroup analysis, Fairbank scale and
      preoperative combined injuries were used. Follow-up MRIs were also available for
      31(75.6%) patients and we searched for relations between MRI findings and
      clinical results. Significant improvements in subjective, objective scores
      (p<0.0001), and stability (p<0.0001) were observed between pre-revision surgery
      and final follow-up results. In the subgroup analysis according to the
      degenerative change, the mild group achieved better clinical results than the
      severe group (p=0.015 and 0.035, respectively). In the subgroup analysis
      according to the combined injuries, no significant difference was observed
      between 2 groups in terms of final follow-up Lysholm and IKDC subjective scores
      (p=0.083 and 0.085, respectively). No relation was found between clinical or
      stability results and MRI findings (p=0.26~0.99). Our results show that the
      severities of combined injuries were not correlated with clinical results, but
      the severities of degenerative changes were correlated with clinical results and
      that results were better in the no or mildly degenerated group. We also found
      that MRI is helpful for evaluating revision ACL, but that no relation was found
      between clinical or stability results and MRI findings of the graft after
      revision surgery.

PMID- 21185731
TI  - Phagocytosis of spermatozoa by epithelial cells in the vagina of the lizard
      Hemidactylus mabouia (Reptilia, Squamata).
AB  - Hemidactylus mabouia is an Africa oviparous lizard that is now distributed on
      other continents and has been introduced to Brazil. In the majority of reptiles,
      the females have the ability to store spermatozoa in specialized regions of the
      genital tract. Considering that in H. mabouia the storage of spermatozoa is
      restricted to the region of the uterine tube, in this study we utilized optical
      and transmission electron microscopy to investigate the processes related to the
      large number of spermatozoa in the vagina. Although it was possible to visualize
      spermatozoa in the vagina, an ultrastructural analysis of the region revealed
      that significant phagocytosis occurs, which is mediated by the epithelial cells.
      Such a process indicates that the anterior portion of the vagina is related to
      the elimination of supernumerary or deficient spermatozoa and not storage.

PMID- 21185730
TI  - Synthesis and in vivo evaluation of 18F-fluoroethyl GF120918 and XR9576 as
      positron emission tomography probes for assessing the function of drug efflux
      transporters.
AB  - The purpose of this study was to synthesize two new positron emission tomography
      (PET) probes, N-(4-(2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2
      isoquinolinyl)ethyl)phenyl)-9,10-dihydro-5-[18F]fluoroethoxy-9-oxo-4-acridine
      carboxamide ([18F]3) and quinoline-3-carboxylic acid [2-(4-{2-[7-(2
      [18F]fluoroethoxy)-6-methoxy-3,4-dihydro-1H-isoquinolin-2
      yl]ethyl}phenylcarbamoyl)-4,5-dimethoxyphenyl]amide ([18F]4), and to evaluate the
      potential of these PET probes for assessing the function of two major drug efflux
      transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP).
      [18F]3 and [18F]4 were synthesized by 18F-alkylation of each O-desmethyl
      precursor with [18F]2-fluoroethyl bromide for injection as PET probes. In vitro
      accumulation assay showed that treatment with P-gp/BCRP inhibitors (1 and 2)
      enhanced the intracellular accumulation capacity of P-gp- and BCRP-overexpressing
      MES-SA/Dx5 cells. In PET studies, the uptake (AUC(brain[0-)60 (min])) of [18F]3
      and [18F]4 in wild-type mice co-injected with 1 were approximately sevenfold
      higher than that in wild-type mice, and the uptake of [18F]3 and [18F]4 in P
      gp/Bcrp knockout mice were eight- to ninefold higher than that in wild-type mice.
      The increased uptake of [18F]3 and [18F]4 was similar to that of parent compounds
      ([11C]1 and [11C]2) previously described, indicating that radioactivity levels in
      the brain after injection of [18F]3 and [18F]4 are related to the function of
      drug efflux transporters. Also, these results suggest that the structural
      difference between parent compounds ([11C]1 and [11C]2) and fluoroethyl analogs
      ([18F]3 and [18F]4) do not obviously affect the potency against drug efflux
      transporters. In metabolite analysis of mice, the unchanged form in the brain and
      plasma at 60 min after co-injection of [18F]4 plus 1 were higher (95% for brain;
      81% for plasma) than that after co-injection of [18F]3 plus 1. [18F]4 is a
      promising PET probe to assess the function of drug efflux transporters.

PMID- 21185732
TI  - (99m)Tc Auger electrons--analysis on the effects of low absorbed doses by
      computational methods.
AB  - We describe here the use of computational methods for evaluation of the low dose
      effects on human fibroblasts after irradiation with Technetium-99m ((99m)Tc)
      Auger electrons. The results suggest a parabolic relationship between the
      irradiation of fibroblasts with (99m)Tc Auger electrons and the total absorbed
      dose. Additionally, the results on very low absorbed doses may be explained by
      the bystander effect, which has been implicated on the cell's effects at low
      doses. Further in vitro evaluation will be worthwhile to clarify these findings.

PMID- 21185733
TI  - The validity of preoperative lymph node staging guidelines of European Society of
      Thoracic Surgeons in non-small-cell lung cancer patients.
AB  - OBJECTIVE: The European Society of Thoracic Surgeons (ESTS) has proposed
      preoperative lymph-node staging guidelines (LNSGs) for non-small-cell lung cancer
      (NSCLC) based on the introduction of new staging modalities into clinical
      practice. The validity of these guidelines was assessed. METHODS: Among the
      patients (n=185) with histologically confirmed NSCLC diagnosed between 2007 and
      2009, who were suitable for thoracotomy, the 168 who underwent computed
      tomography (CT) of the chest and CT-integrated positron emission tomography (PET
      CT) were included in the study. The preoperative mediastinal stage was confirmed
      by mediastinoscopy in all patients. A thoracotomy was done for mediastinoscopy
      negative patients. The mediastinal staging results were adapted to the ESTS-LNSG
      (direct thoracotomy for T1-2 N0 tumour according to CT and PET-CT and invasive
      staging for others) and the validity of the guidelines was tested. RESULTS: In
      this series, the overall mediastinal lymph-node metastasis (MLNM) prevalence was
      29.2%. If the guidelines had been applied, thoracotomy without invasive
      mediastinal staging would have been done in only 11 (6.5%) patients, and no MLNM
      would have been detected. Mediastinoscopy would have been performed in 157
      patients and MLNM would have been found in 41 (26%). In the 116 mediastinoscopy
      negative patients, MLNM would have been detected after thoracotomy in an
      additional eight patients. Thus, the sensitivity, specificity, and positive and
      negative predictive values of the guidelines were calculated as 84%, 100%, 100%
      and 94%, respectively. CONCLUSIONS: The preoperative LNSGs for NSCLC proposed by
      the ESTS are effective.

PMID- 21185734
TI  - Determining the appropriate sleeve lobectomy versus pneumonectomy ratio in
      central non-small cell lung cancer patients: an audit of an aggressive policy of
      pneumonectomy avoidance.
AB  - OBJECTIVE: To study the outcomes of broncho +/- angioplastic sleeve lobectomy
      (SL) versus pneumonectomy (PN), and the PN:SL ratio after an aggressive policy of
      parenchyma-sparing surgery to improve postoperative complications rate and long
      term quality of life (QoL). METHODS: A prospective study was conducted in 490
      patients with non-small cell lung cancer between 2005 and 2009. All patients not
      suitable for standard lobectomy were scheduled for SL, if possible, or for PN;
      eight patients with functional impairment were directly scheduled for SL.
      RESULTS: Of 76 procedures, 21 (4%) were PN and 55 (11%) SL (29 bronchoplastic,
      seven bronchovascular, seven angioplastic; 11 extended to more than one lobe).
      There were no surgical, oncological or physiological preoperative differences
      between the groups. The 5-year PN:SL ratio was 1:2.6 (2005: 1:2.1; 2006: 1:2.6;
      2007: 1:3.6; 2008: 1:3; 2009: 1:3.5). SL and PN mortality were 2 (3.6%) and 1
      (5%), respectively. Postoperative complications occurred in 18 (32%) SL and 7
      (33%) PN patients. pN1 (p = 0.04), vascular reconstruction and upper-left SL were
      risk factors for postoperative complications of SL (p = 0.03) but were not
      detected as a mortality risk. Overall 5-year survival was 61% for SL and 31% for
      PN. Survival at 5 years was significantly higher for SL (p = 0.03, Kaplan-Meier).
      Age <70 years and SL were positive factors for long-term survival. In
      multivariate modelling, both remained positive factors. Surviving PN patients
      experienced significantly greater loss of respiratory function and lower QoL than
      those who avoided this surgery (preoperative score, PN vs SL: 52 vs 51; 3 months,
      41 vs 43; and 6 months, 42 vs 51, p = 0.04). The adjuvant treatment complement
      was higher in SL at 34 (62%) than at PN 10 (47%). The side effects of this
      treatment were more frequent in patients with more extirpated parenchyma (p =
      0.04). CONCLUSIONS: Parenchyma-sparing procedures can reduce the PN rate to less
      than 10%. A PN:SL index lower than 1:1.5 as a quality standard in a specialised
      thoracic unit should encourage the use of broncho-angioplastic procedures and
      improve patient outcomes. Long-term survival, QoL, postoperative lung function
      test and tolerance of adjuvant therapies are significantly better after SL than
      PN intervention.

PMID- 21185735
TI  - Identifying the educational needs of menopausal women: a feasibility study.
AB  - BACKGROUND: The goal of this project was to identify the educational needs of
      menopausal women and test the feasibility of an online self management program
      based on social learning theory. METHODS: The four stages included 1) a needs
      assessment using a) focus groups with 24 women ages 40 to 55 and b) phone
      interviews with eight health experts; 2) the use of concept mapping methodology
      for quantifying qualitative data from stage 1 to identify the core programmatic
      concepts; 3) development of a demonstration program; and 4) a pilot study with 35
      women and 9 health experts to assess knowledge gained and program satisfaction.
      RESULTS: Results show that women desire more information about normalcy of
      menopause and symptom management and found the program to meet a need for
      menopausal education otherwise perceived as unavailable. The women significantly
      increased their menopausal knowledge after brief exposure (t(34) = 3.64; p =
      .001). CONCLUSION: This project provides support for an online health education
      program for menopausal women and content ideas for inclusion in women's health
      education curriculum.

PMID- 21185736
TI  - Gender differences in stroke care and outcomes in Ontario.
AB  - BACKGROUND: Studies of potential gender differences in stroke care and outcomes
      have yielded inconsistent findings. The Project for an Ontario Women's Health
      Evidence-based Report study measured established stroke care indicators in a
      large, representative sample of women and men with stroke or transient ischemic
      attack (TIA) admitted to acute care institutions in the province of Ontario,
      Canada. METHODS: The Registry of the Canadian Stroke Network performs a biennial
      audit on a random sample of 20% of patients with stroke or TIA seen at more than
      150 acute care institutions across Ontario. We used data from the 2004/05 audit
      to compare stroke care by gender, with stratification by age and neighborhood
      income. RESULTS: The sample consisted of 4,046 patients (51% women). There were
      no significant gender differences in the use of thrombolysis, neuroimaging,
      carotid imaging, dysphagia screening, antithrombotic therapy, or neurology and
      other consultations. Women with ischemic stroke or TIA were less likely than men
      to be prescribed statins or undergo carotid imaging and endarterectomy within 6
      months of stroke; women were more likely than men to receive antihypertensives.
      There were no significant gender differences in readmission or mortality rates
      after stroke. INTERPRETATION: In this population-based study, we found little
      evidence of gender differences in stroke care or outcomes other than lipid
      lowering therapy, carotid imaging, and endarterectomy. Further study is needed to
      assess the contribution of the provincial stroke strategy in eliminating gender
      differences in management of acute stroke and to better understand and target
      remaining gender differences in management.

PMID- 21185737
TI  - Increasing discussions of intimate partner violence in prenatal care using Video
      Doctor plus Provider Cueing: a randomized, controlled trial.
AB  - PURPOSE: To report the effectiveness of a prenatal intervention and to provide
      evidence that prenatal visits provide an opportune time for health assessment and
      counseling with abused women. METHODS: Fifty ethnically diverse pregnant women
      who presented for routine prenatal care and who also reported being at risk for
      intimate partner violence (IPV) were recruited to the study. Participants were
      assigned to either usual care or the Video Doctor plus Provider Cueing
      intervention. At baseline and 1 month later at another routine prenatal visit,
      intervention group participants received a 15-minute Video Doctor assessment and
      interactive tailored counseling. Their providers received a printed Cue Sheet
      alert and suggested counseling statements. MAIN FINDINGS: Participants in the
      intervention group were significantly more likely to report provider-patient
      discussions of IPV compared with participants receiving usual care at baseline
      (81.8% vs. 16.7%; p < .001) and at the 1-month follow-up (70.0% vs. 23.5%; p =
      .005). Summing the number of patient-provider discussions across the two visits
      at baseline and 1 month later, intervention participants were significantly more
      likely to have IPV risk discussion with their providers at one or both visits
      (90.0% vs. 23.6%; p < .001) compared with the participants who received usual
      care. When specifically asked about the helpfulness of these IPV-related
      discussions, 20 out of 22 (90.9%) participants rated the discussion as helpful or
      very helpful at baseline and all 18 (100%) participants rated the discussion as
      helpful or very helpful at the 1-month follow-up. CONCLUSION: Video Doctor plus
      Provider Cueing intervention significantly increases the likelihood of provider
      patient IPV discussion with pregnant women with a history of abuse.

PMID- 21185738
TI  - Effects of combination tocopherols and alpha lipoic acid therapy on oxidative
      stress and inflammatory biomarkers in chronic kidney disease.
AB  - OBJECTIVE: Although increased oxidative stress and inflammation are highly
      prevalent in chronic kidney disease (CKD), few studies have investigated whether
      oral antioxidant therapy can alter markers of inflammation or oxidative stress in
      patients with CKD. The purpose of this study was to investigate whether a
      combination of mixed tocopherols and alpha lipoic acid (ALA) would alter
      biomarkers of oxidative stress and inflammation in subjects with stage 3 to 4
      CKD. METHODS: This was a prospective, randomized, double-blind, placebo
      controlled pilot trial. In all, 62 subjects were enrolled and were randomly
      assigned to receive a combination of mixed tocopherols 666 IU/day, in addition to
      ALA 600 mg/day, or their matching placebos for a total of 8 weeks. Plasma F(2)
      isoprostane and protein thiol concentration were measured as biomarkers of
      oxidative stress, and C-reactive protein and interleukin-6 concentration as
      biomarkers of systemic inflammation. RESULTS: There were no significant
      differences in demographics, diabetic status, or estimated glomerular filtration
      rate between study treatment and placebo groups at baseline. Of the 62 randomized
      subjects, 58 (93%) completed the study protocol. After 2 months of treatment,
      there were no significant changes in the concentrations of F(2)-isoprostanes,
      protein thiols, C-reactive protein, and interleukin-6 with respect to treatment
      with mixed tocopherols and ALA as compared with matching placebos, whether
      analyzed as intention to treat or as treated. Diabetic status and baseline body
      mass index did not influence the results. CONCLUSIONS: Combination of oral mixed
      tocopherols and ALA treatment for 2 months does not influence biomarkers of
      oxidative stress and inflammation in patients with stage 3 to 4 CKD.

PMID- 21185739
TI  - Three months of regular gum chewing neither alleviates xerostomia nor reduces
      overhydration in chronic hemodialysis patients.
AB  - INTRODUCTION AND AIMS: Gum chewing has been known to be a part of adjunctive
      medical therapy for cancer-related xerostomia. Nonadherence to fluid restriction
      in hemodialysis (HD) patients brought about by unrestricted thirst and xerostomia
      leads to excessive interdialytic weight gain (IWG). The effectiveness of gum
      chewing in reducing thirst in HD patients has till recently been evaluated by
      only a single study with short 2-week intervention period. The aim of the present
      study was to assess the effect of 3 months of regular use of sugar-free chewing
      gum on xerostomia, thirst, and hydration and nutritional status in HD patients.
      METHODS: A prospective pre/post (3 + 1 month[s]) study including 38 chronic HD
      patients (14 women, 17 men; mean age, 59 +/- 10 years; time on dialysis, 48 +/-
      45 months) with mean mid-week IWG of >1 kg, persistent xerostomia, and/or thirst
      was conducted. Seven patients did not complete the study including 3 because of
      suspected side effects of gum chewing (diarrhea or paradoxically increased
      thirst). After a 2-week run-in period, the subjects received a specified number
      of packs of low-tack, sugar-free chewing gum and specially designed diaries.
      Basic biochemistry and multifrequency electric bioimpedance were performed a
      total of 8 times, that is, at baseline and after each month of the intervention
      period, both before and after dialysis. Questionnaires related to xerostomia and
      thirst were filled in by the patients at baseline, at the end of the intervention
      period, and 1 month later. Body weight (for IWG assessment) and blood pressure
      were measured at the start of each dialysis for the whole duration of the study.
      RESULTS: The mean number of chewing gum pellets used during the first and the
      third month of the study was 137 +/- 56 and 139 +/- 59, respectively. The
      patients did not report experiencing any changes in the intensity of xerostomia
      and thirst during the study. Total body water content assessed with bioimpedance
      did not decrease (41.9 +/- 8.9 kg at baseline vs. 42.7 +/- 9.1 kg at the end of
      the intervention period). Moreover, no changes in extracellular mass (31.9 +/-
      6.4 kg vs. 32.6 +/- 6.6 kg), extracellular water (18.0 +/- 5.2 kg vs. 18.3 +/-
      5.0 kg), and phase angle (4.6 +/- 0.8 vs. 4.6 +/- 0.8) were observed. Mean IWG
      between 2 mid-weekly HD sessions also did not change (2.3 +/- 0.8 kg at baseline
      vs. 2.3 +/- 0.9 kg at the end of the intervention period). No significant changes
      in thirst and xerostomia were observed 4 weeks after the end of the intervention
      period; however, mean IWG between 2 mid-weekly HD sessions increased to 2.8 +/-
      1.0 kg (P < .001). CONCLUSIONS: Regular gum chewing is known to be well tolerated
      by most HD patients; however, it does not lead to the alleviation of xerostomia
      or excessive thirst and does not reduce IWG or improve hydration status.

PMID- 21185740
TI  - Dietary intake in hemodialysis patients does not reflect a heart healthy diet.
AB  - OBJECTIVE: Cardiovascular disease is highly prevalent and has a major effect on
      morbidity and mortality in patients undergoing maintenance hemodialysis (MHD).
      Dietary factors that may contribute to cardiovascular disease have not been well
      studied in this population. We hypothesize that dietary intake in this population
      does not meet the guidelines for cardiovascular risk reduction. DESIGN: A cross
      sectional study was completed using the validated "Block Dialysis 1 Food
      Frequency Questionnaire" to assess dietary intake of MHD patients. SETTING AND
      PATIENTS: A total of 70 patients undergoing MHD at our outpatient dialysis center
      completed the questionnaire under the supervision of a trained dietitian. The
      population consisted of 38 men and 32 women. MAIN OUTCOME MEASURE: Dietary intake
      was the main outcome measure, with a focus on calories, soluble fiber, saturated
      fatty acid (SFA), unsaturated fatty acid intake (UFA), and protein. RESULTS: The
      mean fiber intake was 10.77 (+/-5.87) g/day, and only 2 of 71 (2.9%) were in
      compliance with the recommended daily intake of >25 g/day. As percentage of total
      calories, of the 70 patients, 5 (7.1%) had a fat intake of <30%, 22 (31.4%) had
      SFA intake of <10%, 64 (91.4%) had a UFA of <=30%, 22 (31.4%) had a protein-based
      diet of >=15%, and 66 (94.3%) had a carbohydrate diet of <60%. CONCLUSIONS: Most
      patients did not meet the dietary guidelines for reducing the risk of
      cardiovascular disease. Substituting UFA or soluble fiber for SFA improves low
      density lipoprotein (LDL) cholesterol levels without negative effects on other
      lipid parameters.

PMID- 21185741
TI  - Predominant vasogenic edema in a patient with fatal cerebral air embolism.
AB  - Cerebral air embolism (CAE) is a rare neurologic complication that can occur in
      patients undergoing various medical procedures or trauma. CAE can sometimes
      result in death caused by severe brain edema. In spite of these implications, the
      pathophysiologic mechanisms and radiologic features of fatal CAE remain to be
      elucidated. In this case report, a patient with carcinomatous pleuritis lost
      consciousness and developed quadriplegia and had generalized seizures during
      intrathoracic lavage. Serial computed tomography (CT) revealed the presence of
      air in intracranial blood vessels following severe brain edema; these are
      typically observed on the CT scans of patients with fatal CAE. Diffusion-weighted
      imaging (DWI) of the brain obtained at 24 hours after the onset of CAE revealed
      scattered cortical gyriform high signal intensity often observed in CAE cases,
      whereas the apparent diffusion coefficient and T2-weighted imaging revealed
      diffuse hyperintensity in the subcortical deep white matter, indicating vasogenic
      edema. Our case showed predominant vasogenic edema rather than cortical ischemic
      changes in the subcortical deep white matter area. These findings indicate that
      diffuse subcortical vasogenic edema could be the main cause of mortality in fatal
      CAE.

PMID- 21185742
TI  - Variations of blood pressure in stroke unit patients may result from alternating
      body positions.
AB  - BACKGROUND: Blood pressure (BP) is one of the major vital parameters monitored in
      the stroke unit. The accuracy of indirect BP measurement is strongly influenced
      by the position of both patient and arm during the measurement. Acute stroke
      patients are often nursed in lateral decubitus positions. The effect of these
      alternating body positions in relation to affected body side on the outcome and
      reliability of BP readings in acute stroke patients is unknown. METHODS: An
      automatic oscillometric BP device was used. BP was measured in both arms in the
      (back) supine and both lateral decubitus positions. RESULTS: In total, 54
      consecutive acute stroke patients were included. Thirty-five patients had right
      sided deficits and 19 patients had left-sided deficits. Supine BP readings were
      similar in the right and left arms regardless of side of deficit. Measurements of
      BP in the lateral decubitus positions resulted in significantly lower BP readings
      in the uppermost arm (around 12 mm Hg in both arms) and significantly higher
      readings in the right lowermost arm (around 6 mm Hg) compared to the supine
      position. This effect seemed less pronounced when the left lowermost arm was
      measured. There was no relation between change of BP readings in various lateral
      positions and side of stroke. CONCLUSIONS: Alternating lateral decubitus
      positions according to nursing standards in acute stroke patients lead to a mean
      18 mm Hg BP fluctuation. This may largely be explained by hydrostatic pressure
      effects, partly by anatomic factors in the left lowermost arm, but not by the
      side of stroke.

PMID- 21185743
TI  - Cerebral venous sinus thrombosis in an adult patient presenting as headache and
      acute subdural hematoma.
AB  - We report a 55-year-old man with cerebral venous sinus thrombosis presenting as
      acute subdural hematoma. He was treated with an intravenous infusion of heparin
      sodium and the occluded superior sagittal sinus was recanalized. According to our
      literature review, acute subdural hematoma caused by cerebral venous sinus
      thrombosis is relatively rare, and only a single case has reported thus far. We
      speculate that dehydration was the reason for cerebral venous sinus thrombosis in
      the present case, and the sudden rise in intracranial pressure in addition to
      hemodynamic stress caused by cerebral venous sinus thrombosis resulted in the
      collapse of a bridging vein and caused an acute subdural hematoma.

PMID- 21185745
TI  - Re: Inherited cardiomyopathies mimicking arrhythmogenic right ventricular
      cardiomyopathy.

PMID- 21185744
TI  - The prognosis for aphasia in stroke.
AB  - BACKGROUND: Aphasia is a disabling chronic stroke symptom, but the prognosis for
      patients presenting with aphasia in the hyperacute window has not been well
      characterized. The purpose of this study is to assess the prognosis for recovery
      of language function in subjects presenting with aphasia caused by ischemic
      stroke within 12 hours of symptom onset. METHODS: Subjects presenting with
      aphasia were identified from a prospective cohort study of 669 subjects
      presenting emergently with acute stroke. Subjects were characterized by
      demographics, serial clinical examinations, unenhanced computed tomography, and
      computed tomographic angiography. Aphasia severity was assessed by National
      Institutes of Health Stroke Scale (NIHSS) examinations performed at baseline,
      discharge, and 6 months. Demographic, clinical, and imaging factors were assessed
      for prognostic impact. RESULTS: Aphasia was present in 30% of subjects (n = 204).
      Of the 166 aphasic patients alive at discharge (median 5 days), aphasia improved
      in 57% and resolved in 38%. In the 102 aphasic subjects evaluated at 6 months,
      aphasia improved in 86% and completely resolved in 74% of subjects. Among aphasic
      subjects with "mild" stroke (initial NIHSS <5), aphasia resolved in 90% of
      subjects by 6 months. Factors significantly associated with better outcome
      included clinically and radiographically smaller strokes and lower prestroke
      disability. CONCLUSIONS: The prognosis for full recovery of aphasia present in
      the hyperacute window is good. Radiographic and clinical markers indicating
      lesser extent of ischemia correlated to greater recovery. Given the excellent
      prognosis for language recovery in mild stroke, the net benefit of thrombolysis
      in such cases is uncertain.

PMID- 21185746
TI  - Scopulariopsis brevicaulis infection of prosthetic valve resembling aspergilloma
      on histopathology.
AB  - Fungal prosthetic valve endocarditis is an infrequent but serious complication of
      valve replacement surgery. Approximately 75% of patients are affected with
      Candida species. Scopulariopsis species affecting prosthetic valve is rarely
      reported in the literature.

PMID- 21185748
TI  - A collaborative HIV prevention and education initiative in a faith-based setting.

PMID- 21185747
TI  - Differential proteoglycan and hyaluronan distribution in calcified aortic valves.
AB  - BACKGROUND: While the prevalence of calcified aortic valve disease continues to
      rise and no pharmacological treatments exist, little is known regarding the
      pathogenesis of the disease. Proteoglycans and the glycosaminoglycan hyaluronan
      are involved in calcification in arteriosclerosis and their characterization in
      calcified aortic valves may lend insight into the pathogenesis of the disease.
      METHODS: Fourteen calcified aortic valves removed during valve replacement
      surgery were immunohistochemically stained for the proteoglycans decorin,
      biglycan, and versican, as well as the glycosaminoglycan hyaluronan. Staining
      intensity was evaluated in the following regions of interest: center of calcified
      nodule, edge of nodule, tissue directly surrounding the nodule; center and tissue
      surrounding small "prenodules"; and fibrosa layer of normal regions of the
      leaflet distanced from the nodule. RESULTS: Decorin, biglycan, and versican, as
      well as hyaluronan, were abundantly present immediately surrounding the calcified
      nodules, but minimally within the nodule itself. Expression of decorin and
      biglycan in and surrounding prenodules was greater than in the edge and center
      regions of mature nodules. The levels of expression of the proteoglycans and
      hyaluronan were highly correlated with one another in the different regions of
      the valve. CONCLUSIONS: The three proteoglycans and hyaluronan demonstrated
      distinctive localization relative to nodules within calcified aortic valves,
      where they likely mediate lipid retention, cell proliferation, and extracellular
      matrix remodeling, and motivate further study. Comparisons between expression of
      these components in mature nodules and prenodules suggest distinct roles for
      these components in nodule progression, especially in the tissues surrounding the
      nodules.

PMID- 21185749
TI  - Binational care-seeking behavior and health-related quality of life among HIV
      infected Latinos in the U.S.-Mexico border region.
AB  - Although binational health care-seeking is common among HIV-infected Latinos
      living near the U.S.-Mexico border, information is lacking on whether regional
      indicators of health access are associated with Health-Related Quality of Life
      (HRQL). This study examined health care-seeking behaviors across four HRQL
      domains (emotional well-being, cognitive functioning, physical functioning, and
      pain) using linear regression. HIV-infected Latinos (n = 239) were recruited from
      U.S. community clinics situated near the border shared by California with Mexico.
      In general, the Spanish-speaking (81%) and male-dominant (84%) population had
      positive indicators of HRQL. AIDS diagnosis predicted poorer HRQL (cognitive
      functioning, physical functioning, and pain), as did receipt of traditional
      medications and/or herbs in Mexico (physical functioning and pain). Staying for 1
      or more months in Mexico in the past year was associated with higher cognitive
      functioning and less pain. Border-related factors were inconsistently implicated
      in HRQL measures. Improved understanding of complementary and alternative
      medicine usage by HIV-infected Latinos is warranted.

PMID- 21185750
TI  - HIV and Mexican migrant workers in the United States: a review applying the
      vulnerable populations conceptual model.
AB  - Mexican migrant workers residing in the United States are a vulnerable population
      at high risk for HIV infection. This article critically appraises the published
      data surrounding HIV prevalence in this vulnerable group, as seen through the
      lens of the Vulnerable Populations Conceptual Model. This model demonstrates how
      exposure to risk and resource availability affect health status. The health
      status of Mexican migrants in the United States is compromised by a number of
      factors that increase risk of HIV: limited access to health services, multiple
      sexual partners, low rates of condom use, men having sex with men, and lay
      injection practices. Migration from Mexico to the United States has increased the
      prevalence of HIV in rural Mexico, making this an issue of urgent binational
      concern. This review highlights the implications for further nursing research,
      practice, and policy.

PMID- 21185751
TI  - Addressing the slow uptake of HIV testing in Malawi: the role of stigma, self
      efficacy, and knowledge in the Malawi BRIDGE Project.
AB  - This study was carried out to test the hypothesis that HIV-related stigma would
      function as a barrier to uptake of HIV testing and that knowledge and self
      efficacy would serve as facilitators. We also hypothesized that exposure to a
      behavior-change campaign would be associated with lower levels of stigma and
      higher levels of knowledge and self-efficacy. We conducted two separate cross
      sectional surveys as part of the Malawi BRIDGE Project, including one at baseline
      in eight districts (n = 891), and another at mid-term in four districts in Malawi
      (n = 881). HIV-related knowledge, self-efficacy, and lack of stigma were
      positively associated with HIV testing. A positive association was also found
      between program exposure, on one hand, and knowledge, self-efficacy, and lack of
      stigma, on the other. These findings suggest that important psychosocial
      variables are linked with people's likelihood of HIV testing, and that these
      variables may be influenced by behavior-change programs.

PMID- 21185752
TI  - Pharmacogenomics of warfarin dose requirements in Hispanics.
AB  - While Hispanics are the largest and most rapidly growing minority population in
      the United States, they are underrepresented in pharmacogenomic studies with
      warfarin. We sought to determine the combination of clinical and genetic
      influences of warfarin dose requirements in Hispanics. In addition, we tested the
      performance of published warfarin dosing algorithms derived from largely non
      Hispanic cohorts in an inner-city U.S. Hispanic population. Genetic samples and
      clinical data were obtained from 50 Hispanics on a stable dose of warfarin. The
      contribution of cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase
      complex-1 (VKORC1) genotypes and clinical factors to warfarin dose requirements
      was determined. The correlation between the predicted dose using published
      algorithms and therapeutic dose was also assessed. Compared to the VKORC1-1639 GG
      genotype, warfarin dose requirements were 30% and 62% lower with the GA and AA
      genotypes, respectively (p=0.001). The combination of the VKORC1-1639G>A and
      CYP2C9 genotypes and clinical factors explained 56% of the inter-patient
      variability in warfarin dose. Warfarin dose predicted using algorithms derived
      from mostly non-Hispanic cohorts was significantly correlated with the
      therapeutic dose in our Hispanic cohort (r(2)=0.43 to 0.49; p<0.001); the
      predicted dose was within 1.0 mg/day of the therapeutic dose for 40% to 50% of
      patients. Our data suggest that factors influencing warfarin dose requirements in
      Hispanic Caucasians are similar to those previously described in European
      Caucasians and that dosing algorithms derived from non-Hispanic Caucasian cohorts
      are applicable to Hispanics living in the U.S.

PMID- 21185753
TI  - Lactate-driven equine conditioning programmes.
AB  - Equine conditioning programmes are rarely driven by science. Indeed, the
      scientific literature on conditioning responses often refers to conventional
      technique rather than physiological driving parameters. This, alongside poor
      classification of conditioning protocols, has reduced the possibility of
      comparative data analysis. Recent interest into lactate-driven conditioning
      programmes has driven this review which provides a summary of equine protocols
      used to date and their responses. Key areas identified for further
      standardisation and/or investigation include (1) the treadmill acclimation
      protocol and markers of its efficiency, (2) the design and frequency of
      standardised exercise tests used, and (3) the interpretation of data for the
      development of effective and realistic conditioning programmes.

PMID- 21185754
TI  - Maturation of response time and attentional control in ADHD: evidence from an
      attentional capture paradigm.
AB  - Inattention and hyperactivity/impulsivity are the core symptoms of Attention
      Deficit/Hyperactivity Disorder (ADHD). Slowness, although less known, has been
      also recently reported in children with ADHD and may contribute to their learning
      difficulties. Slow response time and greater response time variability have been
      highlighted by several computerized tasks. The goal of the present work was to
      evaluate the age-related response time in ADHD children and in a group of matched
      control children during an attentional capture paradigm. The study population
      included 75 children with ADHD (aged between 6 and 13) and 75 age- and gender
      matched typical developing children (Control group). The children with ADHD made
      more errors than children on the control group. The response times and the
      response time variability decreased with age in both groups and were
      significantly greater in ADHD than in controls. The distractor effect was similar
      in both groups. The maturation of response times and response time variability
      with age is quite similar in children with ADHD and typical developing children
      but whatever the age-class, children with ADHD were slower and exhibited greater
      response time variability than control children that could explain the variation
      during day-time of attention capacities in ADHD.

PMID- 21185755
TI  - Over-expression of NYGGF4 (PID1) inhibits glucose transport in skeletal myotubes
      by blocking the IRS1/PI3K/AKT insulin pathway.
AB  - INTRODUCTION: Defects in insulin-stimulated glucose uptake in muscle are the
      important early events in the pathogenesis of insulin resistance. NYGGF4 (also
      named PID1) is a recently discovered gene which is suggested to be associated
      with obesity-associated insulin resistance. In this study, we aimed to
      investigate the effects of NYGGF4 on glucose uptake and insulin signaling in rat
      skeletal muscle cells. METHODS: Rat L6 myoblasts were transfected with either an
      empty vector or an NYGGF4-expressing vector and induced to differentiate into
      mature L6 skeletal myotubes. Glucose uptake was determined by measuring uptake of
      2-deoxy-d-[(3)H] glucose. Immunoblotting was performed to detect the
      translocation of insulin-sensitive glucose transporter 4 (GLUT4). Immunoblotting
      was also used to measure phosphorylation and total protein levels of the insulin
      signaling proteins including insulin receptor (IR), insulin receptor substrate 1
      (IRS1), Akt, extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38, and c
      Jun-N-terminal kinase (JNK). RESULTS: NYGGF4 over-expression in L6 skeletal
      myotubes reduced insulin-stimulated glucose uptake and impaired insulin
      stimulated GLUT4 translocation. It also diminished insulin-stimulated tyrosine
      phosphorylation of IRS1 and serine phosphorylation of Akt without affecting the
      phosphorylation of IR, ERK1/2, p38, or JNK. CONCLUSIONS: Over-expression of
      NYGGF4 inhibits glucose transport in skeletal myotubes by blocking the
      IRS1/PI3K/AKT insulin pathway. These observations highlight the potential role of
      NYGGF4 in glucose homeostasis and the development of insulin resistance in
      obesity.

PMID- 21185756
TI  - Identification of the first COG-CDG patient of Indian origin.
AB  - Mutations in the Conserved Oligomeric Golgi (COG) complex give rise to type II
      congenital disorders of glycosylation (CDG). Thus far, mutations have been
      identified in 6 of the 8 COG subunits. Here we present data identifying a
      previously reported CDG-IIx case from Singapore as a new COG4 patient with 2
      novel mutations leading to p.E233X and p.L773R; with p.E233X being a de novo
      mutation. As a result, COG4 protein expression was dramatically reduced, while
      expression of the other subunits remained unaffected. Analysis of serum N-glycans
      revealed deficiencies in both sialylation and galactosylation. Furthermore,
      patient fibroblasts have impaired O-glycosylation. Importantly, patient
      fibroblasts exhibited a delay in Brefeldin A (BFA) induced retrograde transport,
      a common characteristic seen in COG deficiencies.

PMID- 21185757
TI  - Retrobulbar thrombus in a cat with systemic hypertension.
AB  - This report describes a 14-year-old neutered male Norwegian Forest cat that was
      evaluated for a complaint of inappetence, lethargy, and ocular protrusion with
      third eyelid prolapse. The systemic blood pressure was elevated at 205/129 mmHg.
      Fundic examination revealed severe retinal hemorrhage in both eyes. Based on an
      ultrasound study of the retrobulbar area, a thrombus caudal to the right globe
      was suspected. Over 18 days, the cat exhibited significant clinical improvement
      as well as good blood pressure control. To our knowledge this is the first report
      of a retrobulbar thrombus in a cat with systemic hypertension.

PMID- 21185758
TI  - Aortitis and periaortitis in ankylosing spondylitis.
AB  - Aortic involvement is a potential life-threatening complication of ankylosing
      spondylitis, usually occurring late in the course of this frequent disease.
      Inflammatory lesions evolving to fibrosis are primarily localized in the aortic
      root causing regurgitation, but this process can extend into the left atrium
      (subaortic bump) involving the mitral valve and the heart conduction system.
      First, second and third degree atrioventricular blocks are the most common
      conduction alterations described and they can be temporary. Chronic periaortitis
      has been described in ankylosing spondylitis patients. This disease is
      characterized by inflammation evolving to fibrosis and it is localized in the
      periaortic and peri-iliac retroperitoneum. It causes compressive effects on
      ureters and venous, arterial and lymphatic vessels. Its treatment employs
      endoscopic and/or surgical procedures and administration of corticosteroids, even
      in association with immunosuppressive agents. Both aortitis (with conduction
      system alterations) and periaortitis should be kept in mind by the physicians
      because they can significantly influence the prognosis of ankylosing spondylitis
      patients and they can need a rapid treatment.

PMID- 21185759
TI  - [French first results using magnetic resonance-guided focused ultrasound for
      myoma treatment].
AB  - OBJECTIVE: Many women with myomas desire uterine conservation. Magnetic resonance
      guided focused ultrasound surgery (MRgFUS) is a new non-invasive therapy. We
      describe our early results regarding efficacy and safety of MRgFUS for the
      treatment of uterine leiomyomas. PATIENTS AND METHODS: Fifty-two French women,
      over 18 years of age, who were candidates for surgical myomectomy, hysterectomy
      or uterine artery embolization due to symptomatic myomas were treated by MRgFUS
      (ExAblate 2000((r)), InSightec) and followed up for at least 6 months. Intramural
      or subserous myomas with a size between 4-12 cm and a T2 low intensity MRI image
      were selected in women with no abdominal scar and no bowel interposition. The
      modified symptom severity score (SSS) was examined before and after the treatment
      at 6 months. Second treatment rate during the first follow-up year was reported.
      RESULTS: No serious complications were recorded during the treatments or follow
      up period. Seven women had initial failure mostly because of bowel interposition,
      six of them had uterine artery embolisation. The mean modified SSS value for
      patients before MRgFUS was 41/100 and the values diminished significantly to a
      mean value of 22/100. A total of 65% of women had a reduction of at least 10
      points (n=22) (initial score of 41 [29; 62] and 22 [16; 46] at 6 month follow
      up). Good correlation was observed between myomas destruction and the symptoms
      score. During the follow-up period, ten patients (19%) required invasive
      interventions (six hysterectomies, two embolisations and two myomectomies). The
      average reduction in myoma volume determined by MR imaging at 6 months after
      treatment was 14%. This volume reduction is poorly correlated with the myoma's
      treated volume of 36.4% (6-74%). CONCLUSION: MRgFUS can safely be used for
      symptomatic treatment and avoid the need for surgical intervention in most
      patients. Additional follow-up is needed to determine the long-term durability of
      this promising non-invasive approach and to obtain reimbursement.

PMID- 21185760
TI  - [Fetal-pelvic disproportion and X-ray pelvimetry].
AB  - OBJECTIVES: X-ray pelvimetry is a method that not only allows exploring the
      pelvic inlet but also would partially explain the "fetal-pelvic disproportion".
      The aims of this study are to estimate this capacity to actually explain the
      aforementioned disproportion, assessing as well its influence on the follow-up of
      later pregnancies. PATIENTS AND METHODS: A retrospective study was performed in
      Angers' hospital, France. We went back over 11 years and included 90 nulliparous
      patients, all of whom had a C-section due to "fetal-pelvic disproportion". We
      defined a specific sub-group for arrest of labor. RESULTS: Only 55.5% of the
      patients had an unfavorable Magnin's index (<23 cm) and 47.8% were, according to
      it, in the uncertainty - or dystocia - zone. Labor arrest was explained by
      mechanical obstruction (72% of the patients had pelvic abnormalities) and by
      dysfunctional patterns (40% due to a posterior position of the occiput, 18%
      because of hypotonic labor). An important number of elective C-sections (55
      cases) was recorded for subsequent pregnancies. Reasons were bound to X-ray
      pelvimetry (35 cases), the patients' wish (two cases), to maternal pathology
      (four cases), to a hydramnios (three cases) and to the suspicion of fetal
      distress (five cases). DISCUSSION AND CONCLUSIONS: The term "fetal-pelvic
      disproportion" should be carefully used. Some authors used it in case of arrest
      of labor during two hours, a normal dynamic pattern, sufficient cervical dilation
      and, for many, an occipoanterior position.

PMID- 21185761
TI  - [New technologies for genome analysis: Which use in prenatal diagnosis].
AB  - Array-CGH emergence allowed important diagnosis progress, and a better care of
      patients in postnatal. So, there is a great temptation to use it also in prenatal
      diagnosis. The point of view objective is to make a rapid overview of cytogenetic
      diagnosis evolution during the last 50 years, and to show all questions raised by
      the use of array-CGH, and problems that could arise in prenatal diagnosis. While
      array-CGH just comes in genetic laboratories, new diagnosis approaches emerged
      like whole genome sequencing or non-invasive prenatal diagnosis. The 2nd
      objective will be to review all these techniques for a probably close future.

PMID- 21185762
TI  - [Value of ultrasonographic measurement of bladder neck mobility in the management
      of female stress urinary incontinence].
AB  - Transvaginal ultrasound is the first line imaging investigation in gynaecology.
      It was thus introduced for the exploration of female stress urinary incontinence
      at the beginning of the 1980s. Various techniques and parameters of ultrasound
      examination have been used for the assessment of bladder neck mobility. The aim
      of this literature review was to suggest the adequate ultrasound technique to
      study bladder neck mobility. We reviewed articles indexed in MEDLINE dealing with
      urogenital ultrasound and published between 1998 and 2008. The bladder-symphysis
      distance measured by transperineal ultrasound is a reliable and reproductive tool
      to study female stress urinary incontinence. Despite a lack of standardization of
      Valsalva manoeuvre, normal bladder neck mobility is estimated between 15 and 20
      mm. Furthermore, in case of complications from stress urinary incontinence
      surgery, ultrasound is considered as the first line imaging test. Perineal
      ultrasound is an interesting investigation for preoperative assessment of stress
      urinary incontinence or in case of surgery failure or complications. This
      suggests the need for wider diffusion of this technique in urogynecology teams.

PMID- 21185763
TI  - Postmortem serotonin levels in cerebrospinal and pericardial fluids with regard
      to the cause of death in medicolegal autopsy.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter in the central
      nervous system (CNS) and a smooth muscle regulator in the cardiovascular and
      gastrointestinal systems. The present study investigated postmortem 5-HT levels
      in cerebrospinal fluid (CSF) and pericardial fluid (PCF) with regard to the cause
      of death in serial medicolegal autopsy cases within 48 h postmortem (n=351, >20
      years of age). CSF and PCF 5-HT slightly increased during the postmortem period
      (r=0.298 and 0.253, respectively, p<0.001), showing no gender-related difference.
      The CSF level decreased depending on the subject age (r=0.497, p<0.001); however,
      the CSF and PCF levels showed similar findings with regard to the cause of death:
      these levels were significantly higher for sedative-hypnotic drug intoxication
      and hyperthermia (heat stroke), but lower for blunt head injury and hypothermia
      (cold exposure); the cutoff value was estimated as 25.5 ng/ml and 5.0 ng/ml,
      respectively. For other cause of death groups, some cases showed a higher level.
      These findings suggest elevations in CSF and PCF 5-HT levels due to systemic
      toxic or hyperthermic neuronal dysfunction, and systemic stress responses to
      trauma without CNS involvement.

PMID- 21185764
TI  - A picture is worth a thousand words--the utility of 3D visualization illustrated
      by a case of survived pancreatic transection.
AB  - It is one of the most important tasks of the forensic pathologist to explain the
      forensically relevant medical findings to medical non-professionals. However, it
      is often difficult to comment on the nature and potential consequences of organ
      injuries in a comprehensive way to individuals with limited knowledge of anatomy
      and physiology. This rare case of survived pancreatic transaction after kicks to
      the abdomen illustrates how the application of dedicated software programs for
      three-dimensional reconstruction can overcome these difficulties, allowing for
      clear and concise visualization of complex findings.

PMID- 21185765
TI  - Suicidal knife wound to the heart: challenges in reconstructing wound channels
      with post mortem CT and CT-angiography.
AB  - We present a case of an individual who stabbed himself through the heart with a
      large knife. Post mortem computed tomography (CT) and CT-angiography were used to
      assess the stab channel and to reconstruct the sequence of events. After
      penetrating injuries to the chest, both the intra-thoracic organs and the injury
      causing instrument may shift (e.g. from pnemothorax) and render forensic
      reconstructions more challenging. This case report illustrates the potentials and
      the pitfalls of CT for the reconstruction of penetrating injures to the chest.

PMID- 21185766
TI  - Synergistic effect of hydrogen peroxide production and sonochemiluminescence
      under dual frequency ultrasound irradiation.
AB  - The synergistic effect of H(2)O(2) production and sonochemiluminescence (SCL) was
      studied under both orthogonal and opposite dual irradiation at the frequencies of
      28, 584 and 970 kHz and at various acoustic powers. The largest reduction in
      H(2)O(2) production was observed under opposite dual irradiation at a 28/28 kHz
      frequency without considering the acoustic power levels. The largest enhancement
      was observed under dual irradiation at a frequency of 28/970 kHz. This
      enhancement might be due to the increased number of bubbles that underwent
      violent collapse by low frequency ultrasound (28 kHz). These results were also
      confirmed by observing the SCL. Under dual irradiation at relatively high
      frequencies (i.e., 584 and 970 kHz), the synergistic effect was high at low
      acoustic power levels. However, the effect tended to decrease (to the equivalent
      of the calculation from the result of each single irradiation) with increasing
      acoustic power. Unlike dual irradiation coupled with a frequency of 28 kHz, the
      inhibition effect was not observed under dual irradiation at relatively high
      frequencies. With respect to H(2)O(2) production, the production rate constants
      of H(2)O(2) followed the order of 584/584>584/970>28/970~28/584>28/28 kHz, which
      resulted from the fact that the production efficiency of H(2)O(2) at an
      irradiation frequency of 584 kHz was considerably higher than that at other
      frequencies.

PMID- 21185767
TI  - Anterior thigh pain - A case report.

PMID- 21185768
TI  - The slow and fast components of postural sway in chronic neck pain.
AB  - BACKGROUND: Several studies have reported altered postural control in people with
      neck pain. The aim of this study was to increase the understanding of the nature
      of altered postural control in neck pain by studying the slow and fast components
      of body sway. METHODS: Subjects with whiplash associated disorders (WAD, n = 21)
      and chronic non-specific neck pain (NS, n = 24) were compared to healthy controls
      (CON, n = 21) in this cross-sectional study. The magnitudes of the slow and fast
      sway components were assessed in Rhomberg quiet stance for 30 s on a force plate
      with eyes closed. We also investigated associations between postural sway and
      symptoms, self-ratings of functioning and kinesiophobia. RESULTS: Increased
      magnitude of the slow sway component was found in WAD, but not in NS. Greater
      magnitude of the slow component in WAD was associated with poorer physical
      functioning, including balance disturbances, and more severe sensory symptoms.
      CONCLUSIONS: Increased magnitude of the slow sway component implies an aberration
      in sensory feedback or processing of sensory information in WAD. The associations
      between postural sway and self-rated characteristics support the clinical
      validity of the test. Further investigation into NS, involving a longer test time
      is warranted.

PMID- 21185769
TI  - On the origins of nitric oxide.
AB  - Nitric oxide (NO) is widely recognized for its role as signaling compound.
      However, the metabolic mechanisms that determine changes in the level of NO in
      plants are only poorly understood, despite this knowledge being crucial to
      understanding the signal function of NO. To date, at least seven possible
      pathways of NO biosynthesis have been described for plants, although the
      molecular and enzymatic components are resolved for only one of these. Currently,
      this represents the most significant bottleneck for NO research. In this review,
      we provide an overview of the multiplicity of NO production and scavenging
      pathways in plants. Furthermore, we discuss which areas should be focused on in
      future studies to investigate the origin of fluctuations in the level of NO in
      plants.

PMID- 21185770
TI  - Optimizing non-natural protein function with directed evolution.
AB  - Developing technologies such as unnatural amino acid mutagenesis, non-natural
      cofactor engineering, and computational design are generating proteins with novel
      functions; these proteins, however, often do not reach performance targets and
      would benefit from further optimization. Evolutionary methods can complement
      these approaches: recent work combining unnatural amino acid mutagenesis and
      phage selection has created useful proteins of novel composition. Weak initial
      activity in a computationally designed enzyme has been improved by iterative
      rounds of mutagenesis and screening. A marriage of ingenuity and evolution will
      expand the scope of protein function well beyond Mother Nature's designs.

PMID- 21185771
TI  - Spectroscopic (FTIR and FT Raman) analysis and vibrational study on 2,3-dimethyl
      naphthalene using ab-initio HF and DFT calculations.
AB  - A combined experimental and theoretical study on molecular and vibrational
      structure of 2,3-dimethyl naphthalene (2,3-DMN) has been undertaken in the
      present work. The FTIR and FT Raman spectra of 2,3-DMN were recorded in the
      region 4000-100 cm(-1). The optimized geometries were calculated by HF and DFT
      (B3LYP) methods with 6-31++G (d, p), 6-311G (d, p) and 6-311++G (d, p) basis
      sets. The harmonic vibrational frequencies, infrared intensities and Raman
      activities of the 2,3-DMN were evaluated with these methods. After scaling the
      computational wave numbers are in very good agreement with the experimental
      values. A detailed interpretation of the infrared and Raman spectra of 2,3-DMN is
      presented. The effects of substitution of methyl group on the molecule have also
      been discussed.

PMID- 21185772
TI  - Vibrational spectroscopy (FTIR and FTRaman) investigation using ab initio (HF)
      and DFT (B3LYP) calculations on the structure of 3-Bromo phenol.
AB  - The FT-IR and FT-Raman spectra of 3-Bromo phenol (3-BP) molecule have been
      recorded using Bruker IFS 66V spectrometer in the range of 4000-100 cm(-1). The
      molecular geometry and vibrational frequencies in the ground state are calculated
      by using the ab initio Hartree-fock (HF) and DFT (B3LYP) methods with 6-31G (d,
      p) and 6-311G (d, p) basis sets. The computed values of frequencies are scaled
      using a suitable scale factor to yield good coherence with the observed values.
      Making use of the recorded data, the complete vibrational assignments are made
      and analysis of the observed fundamental bands of molecule is carried out. The
      geometries and normal modes of vibrations obtained from ab initio HF and B3LYP
      calculations are in good agreement with the experimentally observed data. The
      differences between the observed and scaled wave number values of most of the
      fundamentals are very small in DFT than HF. The inductive effect of halogen atom
      in the molecule has also been investigated.

PMID- 21185773
TI  - Kinetics of Epstein-Barr virus load and virus-specific CD8+ T cells in acute
      infectious mononucleosis.
AB  - BACKGROUND: During the convalescent phase of acute infectious mononucleosis
      (AIM), Epstein-Barr virus (EBV) load shrinks rapidly in association with a rapid
      decline in the number of EBV-specific CD8(+) T cells. The actual contribution of
      EBV-specific CD8(+) T cells in reducing EBV load, however, is not known.
      OBJECTIVES: To clarify the impact of EBV-specific CD8(+) T cells on the
      contraction of EBV load in AIM, we estimated half-lives of both EBV load and EBV
      specific CD8(+) T cells. STUDY DESIGN: Blood was serially taken from five
      pediatric patients with AIM during the convalescent period, including the very
      early phase, and both EBV load and EBV-specific CD8(+) T cell numbers were
      assayed. RESULTS: EBV load declined rapidly (half-life 1.5 d) during the first 2
      weeks after onset of symptoms. This half-life was seven-fold shorter than that
      reported for CD27(+) memory B cells. Subsequently, the EBV load declined much
      more slowly, with a half-life of 38.7 d. EBV-specific CD8(+) T cell numbers also
      declined concomitantly with the decrease in EBV load. The half-life of EBV
      specific CD8(+) T cells during first 2 weeks was 2.9 d. The number of EBV
      specific CD8(+) T cells and the rate of change of viral load correlated
      significantly (R(2) >= 0.8; p <= 0.02). CONCLUSIONS: The short half-life of EBV
      load, together with the strong correlation between the number of EBV-specific
      CD8(+) T cells and the rate of change of viral load indicates an active role for
      EBV-specific CD8(+) T cells in elimination of EBV in AIM.

PMID- 21185774
TI  - Multicenter comparative study of Epstein-Barr virus DNA quantification for
      virological monitoring in transplanted patients.
AB  - BACKGROUND: EBV-related post-transplant lymphoproliferative diseases are usually
      accompanied by increased EBV DNA in peripheral blood. Monitoring EBV DNAemia is
      the basis for weighing decisions regarding initiation of pre-emptive or anti-EBV
      related tumor therapy. However, the definition of clinically relevant cut-off
      values is hampered by the lack of standardization in EBV DNA testing. OBJECTIVES:
      To estimate inter-laboratory variability and to evaluate the impact of different
      matrices in EBV DNA load determination in Italian laboratories involved in
      monitoring of virus infections in transplanted patients. STUDY DESIGN: Two
      different proficiency panels were distributed among seven centers: the first
      contained cell-associated and cell-free EBVs; the second was prepared by spiking
      both cell-associated and cell-free EBVs in EBV DNA-negative whole blood from EBV
      seropositive healthy donors. Samples were extracted and amplified with different
      methods. Intra-laboratory and inter-laboratory variabilities was evaluated.
      RESULTS: 337 EBV DNA determinations were performed. Sensitivity was 100% for both
      panels, specificity was 100% for the first and 74% for the second panel, where
      whole blood was utilized as the matrix. Discrepant results in the second panel
      were restricted to samples containing low copy numbers. Quantification fell
      within +/-0.5 log in 73% of the determinations. Values for cell-associated
      samples tended to be more heterogeneous than those obtained from cell-free
      samples. Good overall linearity was observed for each sample type; inter
      laboratory variability ranged from 4.71% to 12.86%. CONCLUSIONS: The results of
      this multicenter study indicate that EBV DNAemia may be reliably quantified by
      different laboratories using a variety of commercial and in-house molecular
      assays.

PMID- 21185775
TI  - Impaired mesial synchronization in temporal lobe epilepsy.
AB  - OBJECTIVE: Temporal lobe epilepsy is commonly associated with synchronous, hyper
      synchronous and des-synchronous activity. The aim of the present work is to
      explore synchronization activity in both mesial areas in temporal lobe epileptic
      patients during the interictal state. METHODS: Using a cluster technique, we
      analyzed 17 temporal lobe epilepsy patients' records of foramen ovale electrodes
      activity during the inter-ictal state. RESULTS: There exists a clear tendency in
      the mesial area of the epileptic side to be organized as isolated clusters of
      electrical activity as compared with the contra-lateral side, which is organized
      in the form of large clusters of synchronous activity. The number of
      desynchronized areas is larger in the epileptic side than in the contra-lateral
      side in 16 out of 17 temporal lobe epileptic patients. CONCLUSIONS: The mesial
      area responsible for the seizures is less synchronous than the contra-lateral;
      the different kind of synchronous organization accounts for a lower
      synchronization activity at the epileptic side, suggesting that this lack of
      synchronous cluster organization would favour the appearance of seizures.
      SIGNIFICANCE: Our results shed new light regarding synchronization issues in
      temporal lobe epilepsy and also it would help in reducing drastically the time of
      study.

PMID- 21185776
TI  - Effects of parameters affecting biomass yield and thermal behaviour of Chlorella
      vulgaris.
AB  - Conventional fossil fuels are facing a global challenge which lead scientists to
      explore alternative fuel production from biological sources. The algae-based
      fuels are gaining rapid attention as it has potential to replace petroleum-based
      fuels. An indigenous high lipid producing microalgae was isolated from a
      freshwater pond in the KwaZulu-Natal province of South Africa. The isolate was
      later identified as Chlorella vulgaris, based on partial 28S large subunit
      ribosomal RNA gene sequence. The growth kinetics, pyrolytic characteristics and
      photosynthetic efficiency of Chlorella was evaluated in vitro. The optimized
      conditions for higher biomass yield of the selected strain were at 4% CO(2), 0.5
      g l(-1) NO(3) and 0.04 g l(-1) PO(4), respectively. The pulse amplitude
      modulation results indicated that C. vulgaris could withstand a light intensity
      ranging from 150 to 350 MUmol photons m(-2)s(-1). Further increase in light
      intensity resulted in a decline of the electron transport rate. Carbon fixation
      rate, lipid content and calorific value of C. vulgaris was 6.17 mg l(-1)h(-1),
      21% and 17.44 kJ g(-1), respectively. The pyrolitic studies under inert
      atmosphere at different heating rates of 15, 30, 40 and 50 degrees C min(-1) from
      ambient temperature to 800 degrees C showed that the overall final weight loss
      recorded for the four different heating rates was in the range of 78.9-81%. These
      studies could be useful to appraise the biofuel potential of the isolated C.
      vulgaris strain, which can later be taken for pilot scale production.

PMID- 21185777
TI  - Production of 5-aminolevulinic acid by Propionibacterium acidipropionici
      TISTR442.
AB  - Propionibacterium acidipropionici TISTR442 produced the highest amount of 5
      aminolevulinic acid (ALA) when cultivated in medium supplemented with glycine at
      18g/l. ALA production correlated with ALA synthase activity, whereas ALA
      dehydratase activity was maintained at a low level. ALA yield reached 405mg/l
      after prolonged cultivation for 1 month.

PMID- 21185778
TI  - Improved polyhydroxybutyrate (PHB) production in transgenic tobacco by enhancing
      translation efficiency of bacterial PHB biosynthetic genes.
AB  - Polyhydroxybutyrate [P(3HB)] was produced in the transgenic tobacco harboring the
      genes encoding acetoacetyl-CoA reductase (PhaB) and polyhydroxyalkanoate synthase
      (PhaC) from Ralstonia eutropha (Cupriavidus necator) with optimized codon usage
      for expression in tobacco. P(3HB) contents in the transformants (0.2mg/g dry cell
      weight in average) harboring the codon-optimized phaB gene was twofold higher
      than the control transformants harboring the wild-type phaB gene. The
      immunodetection revealed an increased production of PhaB in leaves, indicating
      that the enhanced expression of PhaB was effective to increase P(3HB) production
      in tobacco. In contrast, codon-optimization of the phaC gene exhibited no
      apparent effect on P(3HB) production. This result suggests that the efficiency of
      PhaB-catalyzed reaction contributed to the flux toward P(3HB) biosynthesis in
      tobacco leaves.

PMID- 21185779
TI  - Shrinkage-free preparation of scaffold-free cartilage-like disk-shaped cell sheet
      using human bone marrow mesenchymal stem cells.
AB  - Aiming for the clinical application of cartilage regeneration, a culture method
      for mesenchymal stem cells (MSCs) derived from human bone marrow to obtain
      scaffold-free cartilage-like disk-shaped sheet of uniform sizes without the
      shrinkage was investigated. A disk-shaped cell sheet having the same diameter as
      that of the membrane without the shrinkage was formed after the cultivation of
      MSCs (18.6 * 10(5)cells/well) for 3 weeks in a cell culture insert (CCI)
      containing a flat membrane whose porosity was 12%, while 6.2 and 31.0 *
      10(5)MSCs/well, respectively, resulted in the shrinkage of the aggregate and the
      hole formation in the center part of the sheet. Cell aggregates shrunk also in a
      96-well plate and CCIs having lower porosity. The disk-shaped cell sheet showed
      the comparable thickness (1.2mm) and sulfated glycosaminoglycan (sGAG) density to
      those of the pellet formed in a pellet culture. The gene expression levels of
      aggrecan and type II collagen in the disk-shaped cell sheet were not lower than
      those in the pellet. In conclusion, the usage of CCI having 12% porosity and 18.6
      * 10(5)MSCs/well could avoid the shrinkage from the formation of the scaffold
      free cartilage-like disk-shaped cell sheet.

PMID- 21185780
TI  - Isolation and identification of lipase producing thermophilic Geobacillus sp. SBS
      4S: cloning and characterization of the lipase.
AB  - A thermophilic microorganism, SBS-4S, was isolated from a hot spring located in
      Gilgit, Northern Areas of Pakistan. It was found to be an aerobic, gram-positive,
      rod-shaped, thermophilic bacterium that grew on various sugars, carboxylic acids
      and hydrocarbons at temperatures between 45 degrees C and 75 degrees C. Complete
      16S rRNA gene sequence of the microorganism exhibited homology to various species
      of genus Geobacillus. A highest homology of 99.8% was found with Geobacillus
      kaustophilus. A partial (0.7 kbp) chaperonin gene sequence also showed a highest
      homology of 99.4% to that of G. kaustophilus whereas biochemical characteristics
      of the microorganism were similar to Geobacillus uzenensis. Based on biochemical
      characterization, 16S rRNA and chaperonin gene sequences, we identified SBS-4S as
      a strain of genus Geobacillus. Strain SBS-4S produced several extracellular
      enzymes including amylase, protease and lipase. The lipase encoding gene was
      cloned, expressed in Escherichia coli and the gene product was characterized. The
      recombinant lipase was optimally active at 60 degrees C with stability at wide pH
      range (6-12). The enzyme activity was enhanced remarkably in the presence of
      Ca(+2). The K(m) and the V(max) for the hydrolysis of p-nitrophenyl acetate were
      3.8mM and 2273 MUmol min(-1)mg(-1), respectively. The ability of the recombinant
      enzyme to be stable at a wide pH range makes it a potential candidate for use in
      industry.

PMID- 21185781
TI  - Intracoronary optical coherence tomography for the assessment of in-stent
      restenosis.
AB  - Optical coherence tomography (OCT) is a novel imaging modality in interventional
      cardiology. With its clear image quality, it has attracted considerable attention
      as a tool to accurately evaluate atherosclerosis and coronary stents in vivo. It
      has a 10-fold higher resolution compared to intravascular ultrasound and utilises
      near-infrared light that requires temporary blood clearance during image
      acquisition. We present a case of in-stent restenosis in a patient five years
      after percutaneous intervention. Optical coherence tomography clearly showed the
      mechanism behind the stent failure and helped appropriately plan the subsequent
      repeat intervention. The technology heralds an exciting advance in the invasive
      assessment of the coronary arteries that will improve our understanding of heart
      disease into the future.

PMID- 21185782
TI  - Numeracy and nurse prescribing: do the standards achieve their aim?
AB  - The new standards of proficiency for Nurse and Midwife prescribers have been in
      place for 4 years and have provided a challenge for education providers and
      students alike. Many students find the pass mark of 100% for numeracy a
      frightening prospect, the way numeracy is assessed can vary across the higher
      education institutions adding to the complexity of the problem. Drug calculation
      remains a challenge for the nursing profession and the standards for numeracy
      assessment in nurse prescribing add more to the debate.

PMID- 21185783
TI  - Increased IL-17 expression is associated with pathology in a bovine model of
      tuberculosis.
AB  - The identification of bovine tuberculosis (bTB) biomarkers in specific stages of
      the disease will contribute to a better understanding of the immunopathology
      associated with tuberculosis and to improve the disease diagnosis and prognosis.
      The aim of this study was to understand the changing profile of the immune
      responses during the course of infection and to identify biomarkers associated
      with pathology. Here we describe the immune response developed in experimentally
      infected cattle with field Mycobacterium bovis strains. Blood samples were taken
      from each animal at different time points after M. bovis intratracheal infection
      and lymphocyte subset activation and cytokine mRNA expression were determined
      from peripheral blood mononuclear cells in response to purified protein
      derivative (PPDB). We found that CD4 and CD8 activation during the early stages
      of infection, together with IL-17 gene expression, were positively associated
      with pathology. The results of this study provide evidences of the role of IL-17
      in the immunopathology of tuberculosis and support the use of IL-17 as a
      potential biomarker with predictive value of prognosis in bTB.

PMID- 21185785
TI  - On the use of donor-derived iNKT cells for adoptive immunotherapy to prevent
      leukemia recurrence in pediatric recipients of HLA haploidentical HSCT for
      hematological malignancies.
AB  - T-cell-depleted hematopoietic stem cell transplantation from an HLA
      haploidentical relative (hHSCT) is a useful therapy for children with high-risk
      leukemia lacking suitable HLA-matched donors. The immune deficiency ensuing hHSCT
      renders patients susceptible to life-threatening infections and disease
      recurrence. Adoptive immunotherapy can restore/enhance early post-transplantation
      immunocompetence of hHSCT recipients. Efforts are directed to identify strategies
      for inducing graft-versus-leukemia (GVL) response, while avoiding graft-versus
      host disease (GVHD) occurrence. CD1d-restricted invariant iNKT cells are innate
      like, lipid-reactive T lymphocytes implicated in the control of innate and
      adaptive immunity. Preclinical data suggest that iNKT cells positively modulate
      both GVL response and GVHD. Our recent findings in a cohort of 22 children given
      hHSCT for different hematological malignancies show that failure to reconstitute
      iNKT cells after transplantation correlates with leukemia relapse. In this
      review, we will discuss potential new options for adoptively transferring donor
      derived iNKT cells into hHSCT recipients in the early post-transplantation period
      to prevent disease recurrence.

PMID- 21185784
TI  - Clinical development of a novel CD1d-binding NKT cell ligand as a vaccine
      adjuvant.
AB  - Natural killer T (NKT) cells are known to play a role against certain microbial
      infections, including malaria and HIV, two major global infectious diseases.
      Strategies that can harness and amplify the immunotherapeutic potential of NKT
      cells can serve as powerful tools in the fight against such diseases. 7DW8-5, a
      novel glycolipid, may be one such tool. The interaction of 7DW8-5 with CD1d
      molecules induces activation of NKT cells, thereby activating various immune
      competent cells including dendritic cells (DCs) to provide a significant adjuvant
      effect for several vaccines. This review discusses the discovery and
      characterization of 7DW8-5 and the practical considerations of its preclinical
      and clinical development as a potential glycolipid adjuvant for candidate malaria
      and HIV vaccines.

PMID- 21185786
TI  - High level of soluble HLA-G in amniotic fluid is correlated with congenital
      transmission of Toxoplasma gondii.
AB  - The expression of human leukocyte antigen (HLA)-G on cytotrophoblast cells
      contributes to maternal-fetal tolerance. Soluble forms of HLA-G (sHLA-G) can be
      detected in amniotic fluid (AF) and a decrease of sHLA-G is known to be
      correlated to fetal loss. In this work we investigated the role of sHLA-G in the
      transplacental passage of the protozoan parasite Toxoplasma gondii, responsible
      for congenital toxoplasmosis in about 30% of fetuses when primary infection (PI)
      occurs during pregnancy. We determined the sHLA-G concentration in 61 AF from
      women with PI and 24 controls. Our results showed higher sHLA-G levels in AF from
      PI than in controls (p<0.001). Moreover sHLA-G level from congenitally infected
      fetuses (n=12) was higher than in fetus in whom congenital infection was ruled
      out (n=49, p<0.05). These data suggest that sHLA-G could participate in
      immunomodulation necessary to avoid fetal loss due to Toxoplasma infection, but
      that over-expression could favor congenital transmission.

PMID- 21185787
TI  - Induction of NKT cell-specific immune responses in cancer tissues after NKT cell
      targeted adoptive immunotherapy.
AB  - Valpha24 natural killer T (NKT) cells have potent anti-tumor activity. We
      performed a phase II clinical study in patients with head and neck squamous cell
      carcinoma (HNSCC) using ex vivo expanded Valpha24 NKT cells and alpha
      galactosylceramide (alphaGalCer; KRN7000)-pulsed antigen-presenting cells (APCs)
      to investigate the efficacy and induction of NKT cell-specific immune responses.
      The subjects were 10 patients with locally recurrent and operable HNSCC. One
      course of nasal submucosal administration of alphaGalCer-pulsed APCs and intra
      arterial infusion of activated NKT cells via tumor-feeding arteries was given
      before salvage surgery. Anti-tumor effects, NKT cell-specific immune responses in
      extirpated cancer tissue and peripheral blood, safety, and pathological effects
      were evaluated. Five cases achieved objective tumor regression. The number of NKT
      cells increased in cancer tissues in 7 cases and was associated with tumor
      regression. The combination therapy induced NKT cell-specific immune responses in
      cancer tissues that were associated with beneficial clinical effects.

PMID- 21185788
TI  - Anterior, posterior and apical vaginal reconstruction with and without bolsters.
AB  - Pelvic-organ-prolapse repair presents unique challenges to the pelvic surgeon.
      Historically, the unacceptable failure rates with traditional procedures have
      instigated the many conceptual and technique changes. Critical analysis of the
      biomechanics of normal and altered anatomy has shifted the primary focus of
      surgeries from the midline of the distal vagina to the interspinous diameter. In
      addition, just as surgeons in other fields have begun to incorporate bolsters
      into various types of repairs, the field of prolapse repair has seen a
      proliferation of materials that are available to help strengthen repairs. Much
      effort, time and significant resources have been invested in improving these
      repairs, but much remains to be learned. The rapid pace of change has prevented
      the development of the type of evidence-based data that are needed to analyse
      accurately the specific risks and benefits of the various available approaches.
      Conceptual changes in the aetiology of pelvic organ prolapse, pelvic biodynamics
      and the specific nature of connective tissue damage have helped to fuel the rapid
      pace of change.

PMID- 21185789
TI  - Preoperative weight loss in high-risk superobese bariatric patients: a computed
      tomography-based analysis.
AB  - BACKGROUND: Superobesity, through organomegaly, excessive adiposity, and
      associated severe co-morbidities, is a recognized risk factor for bariatric
      surgery. Our study examined the utility of preoperative weight loss with a liquid
      low-calorie diet (LCD) as a method of risk reduction. METHODS: All patients with
      a body mass index (BMI) >50 kg/m(2) were instructed to consume a LCD (800 kcal/d)
      with the goal of losing >=10% of their body weight. The co-morbidities were
      monitored. The abdominal wall depth and cross-sectional areas of subcutaneous
      adipose tissue (SAT) at 12 and 20 cm below the costal margin, visceral adipose
      tissue (VAT), and liver volume were measured, using computed tomography, at
      baseline and after completion of the LCD. Laparoscopic gastric bypass was
      performed in all patients. RESULTS: The study included 30 patients (27 men and 3
      women) with a mean age of 53 years (range 34-53). The mean BMI was reduced from
      56 kg/m(2) (range 50-69) at baseline to 49 kg/m(2) (range 43-60) after an average
      of 9 weeks of the LCD. The VAT decreased from a mean of 388 cm(2) to 342 cm(2).
      The abdominal wall depth decreased from 3.6 to 3.2 cm at 12 cm below the costal
      margin and from 3.7 to 3.4 cm at 20 cm. The mean SAT at both 12 and 20 cm below
      the costal margin had decreased from 577 cm(2) and 687 cm(2) to 509 cm(2) and 614
      cm(2), respectively. The liver volume was reduced by 18%. All co-morbidities were
      well controlled at LCD completion. No patient died, and 2 minor complications
      occurred postoperatively. CONCLUSION: The results of our study have shown that
      preoperative LCD is a safe and effective tool leading to a significant decrease
      in liver volume and abdominal wall depth, as well as a reduction in both VAT and
      SAT. Its use might contribute to improved short-term surgical outcomes in high
      risk superobese patients.

PMID- 21185790
TI  - Determination of ciprofloxacin in human plasma using high-performance liquid
      chromatography coupled with fluorescence detection: application to a population
      pharmacokinetics study in children with severe malnutrition.
AB  - Clinical pharmacokinetic studies of ciprofloxacin require accurate and precise
      measurement of plasma drug concentrations. We describe a rapid, selective and
      sensitive HPLC method coupled with fluorescence detection for determination of
      ciprofloxacin in human plasma. Internal standard (IS; sarafloxacin) was added to
      plasma aliquots (200 MUL) prior to protein precipitation with acetonitrile.
      Ciprofloxacin and IS were eluted on a Synergi Max-RP analytical column (150
      mm*4.6 mm i.d., 5 MUm particle size) maintained at 40 degrees C. The mobile phase
      comprised a mixture of aqueous orthophosphoric acid (0.025
      M)/methanol/acetonitrile (75/13/12%, v/v/v); the pH was adjusted to 3.0 with
      triethylamine. A fluorescence detector (excitation/emission wavelength of 278/450
      nm) was used. Retention times for ciprofloxacin and IS were approximately 3.6 and
      7.0 min, respectively. Calibration curves of ciprofloxacin were linear over the
      concentration range of 0.02-4 MUg/mL, with correlation coefficients
      (r(2))>=0.998. Intra- and inter-assay relative standard deviations (SD) were
      <8.0% and accuracy values ranged from 93% to 105% for quality control samples
      (0.2, 1.8 and 3.6 MUg/mL). The mean (SD) extraction recoveries for ciprofloxacin
      from spiked plasma at 0.08, 1.8 and 3.6 MUg/mL were 72.8+/-12.5% (n=5), 83.5+/
      5.2% and 77.7+/-2.0%, respectively (n=8 in both cases). The recovery for IS was
      94.5+/-7.9% (n=15). The limits of detection and quantification were 10 ng/mL and
      20 ng/mL, respectively. Ciprofloxacin was stable in plasma for at least one month
      when stored at -15 degrees C to -25 degrees C and -70 degrees C to -90 degrees C.
      This method was successfully applied to measure plasma ciprofloxacin
      concentrations in a population pharmacokinetics study of ciprofloxacin in
      malnourished children.

PMID- 21185791
TI  - Simultaneous determination of D-amino acids by the coupling method of D-amino
      acid oxidase with high-performance liquid chromatography.
AB  - An enzymatic assay system of D-amino acids was established using the D-amino acid
      oxidase of Schizosaccharomyces pombe. In this method, the enzyme converts the D
      amino acids to the corresponding alpha-keto acids, which are then reacted with
      1,2-diamino-4,5-methylenedioxybenzene (DMB) in an organic solvent. The resultant
      fluorescent compounds are separated and quantified by high-performance liquid
      chromatography (HPLC). Use of an organic solvent following the alpha-keto acid
      modification with DMB prevents the non-enzymatic deamination of L-amino acids,
      which are generally present at much higher concentrations than D-amino acids in
      biological samples. With this method, D-Glu, D-Asn, D-Gln, D-Ala, D-Val, D-Leu, D
      Phe, and D-Ile can be quantified in the order of micromolar, and other D-amino
      acids except D-Asp can be assayed within a sensitivity range of 50-100 MUM. The
      established enzymatic method was used to analyze the d-amino acid contents in
      human urine. The concentration of D-Ser obtained using this enzymatic method (223
      MUM) was in good agreement with that obtained using the conventional HPLC method
      (198 MUM). The enzymatic method also demonstrated that the human urine contained
      5.45 MUM of d-Ala and 0.91 MUM of D-Asn. Both D-amino acids were difficult to be
      identified using the conventional method, because the large signals from L-amino
      acids masked those from d-amino acids. The enzymatic method that we have
      developed can circumvent this problem.

PMID- 21185792
TI  - HPLC MS/MS method for quantification of meprobamate in human plasma: application
      to 24/7 clinical toxicology.
AB  - We described the development and full validation of rapid and accurate liquid
      chromatography method, coupled with tandem mass spectrometry detection, for
      quantification of meprobamate in human plasma with [(13)C-(2)H(3)]-meprobamate as
      internal standard. Plasma pretreatment involved a one-step protein precipitation
      with acetonitrile. Separation was performed by reversed-phase chromatography on a
      Luna MercuryMS C18 (20 mm*4 mm*3 MUm) column using a gradient elution mode. The
      mobile phase was a mix of distilled water containing 0.1% formic acid and
      acetonitrile containing 0.1% formic acid. The selected reaction monitoring
      transitions, in electrospray positive ionization, used for quantification were
      219.2->158.2 m/z and 223.1->161.1m/z for meprobamate and internal standard,
      respectively. Qualification transitions were 219.2->97.0 and 223.1->101.1 m/z for
      meprobamate and internal standard, respectively. The method was linear over the
      concentration range of 1-300 mg/L. The intra- and inter-day precision values were
      below 6.4% and accuracy was within 95.3% and 103.6% for all QC levels (5, 75 and
      200 mg/L). The lower limit of quantification was 1 mg/L. Total analysis time was
      reduced to 6 min including sample preparation. The present method is successfully
      applied to 24/7 clinical toxicology and demonstrated its usefulness to detect
      meprobamate poisoning.

PMID- 21185793
TI  - Human plasma quantification of droperidol and ondansetron used in preventing
      postoperative nausea and vomiting with a LC/ESI/MS/MS method.
AB  - An analytical method based upon liquid chromatography coupled to ion trap mass
      spectrometry (MS) detection with electrospray ionization interface has been
      developed for the simultaneous identification and quantification of droperidol
      and ondansetron in human plasma. The two drugs were isolated from 0.5 mL of
      plasma using a basic liquid-liquid extraction with diethyl ether/heptane (90/10,
      v/v) and tropisetron and haloperidol as internal standards, with satisfactory
      extraction recoveries. They were separated on a 5-MUm C(18) Highpurity column
      (150 mm*2.1 mm I.D.) maintained at 30 degrees C. The elution was achieved
      isocratically with a mobile phase of 2 mM HCOONH(4) pH 3.8 buffer/acetonitrile
      (60/40, v/v) at a flow rate of 200 MUL/min. Data were collected either in full
      scan MS mode at m/z 100-450 or in full-scan MS-MS mode, selecting the [M+H] (+)
      ion at m/z=294.0 for ondansetron, m/z=285.2 for tropisetron, m/z=380.0 for
      droperidol and m/z=376.0 for haloperidol. The most intense daughter ion of
      ondansetron (m/z=212.0) and droperidol (m/z=194.0) were used for quantification.
      Retention times for tropisetron, ondansetron, droperidol and haloperidol were
      2.50, 2.61, 3.10 and 4.68 min, respectively. Calibration curves were linear for
      both compounds in the 0.50-500 ng/mL range. The limits of detection and
      quantification were 0.10 ng/mL and 0.50 ng/mL, respectively. The intra- and inter
      assay precisions were lower than 6.4% and intra- and inter-assay recoveries were
      in the 97.6-101.9% range for the three 3, 30 and 300 ng/mL concentrations. This
      method allows simultaneous and rapid measurement of droperidol and ondansetron,
      which are frequently co-administrated for the prevention of postoperative nausea
      and vomiting.

PMID- 21185794
TI  - Vascular disorders of the liver: recommendations from the Italian Association for
      the Study of the Liver (AISF) ad hoc committee.
AB  - This review summarizes the document elaborated by the Italian Association for the
      Study of the Liver (AISF) ad hoc committee "Vascular disorders of the liver" on
      the primary circulatory liver diseases, which include Budd-Chiari syndrome,
      obstruction of the hepatic portion of the inferior vena cava, portal vein
      thrombosis, sinusoidal obstruction syndrome (veno-occlusive disease) and
      hereditary hemorrhagic telangiectasia. A characteristic of the primary
      circulatory liver diseases is that portal hypertension usually precedes liver
      dysfunction. Significant overlap exists amongst the diseases and risk factors
      that predispose patients to the primary circulatory liver diseases, though the
      pathogenesis of individual diseases varies. Management of the different vascular
      disorders is very peculiar and often multidisciplinary and patients should be
      referred to a tertiary referral centre for optimal care.

PMID- 21185795
TI  - Neurological comorbidities amongst patients with viral hepatitis B: a nationwide
      population-based study.

PMID- 21185797
TI  - [Familial hypocalciuric hypercalcemia: a new mutation].
AB  - Familial hypocalciuric hypercalcemia (FHH) is a cause of hypercalcemia with
      autosomal dominant pattern of inheritance and high penetrance. In most of the
      cases it can be shown to be due to an inactivating mutation on the gene coding
      for the calcium-sensing receptor (CaSR). Heterozygous cases usually do not
      present symptoms and they are diagnosed as an incidental finding. We report three
      affected children with an inactivating heterozygous mutation, p.Phe789del, in
      exon 7 of the calcium-sensing receptor gene (CASR gene), situated in chromosome
      3q21 (Ensembl ENSG00000036828), which results in elevated serum calcium, normal o
      high level of parathyroid hormone (PTH) and reduced urinary excretion with
      hypocalciuria. It is very important to determine the difference between FHH and
      primary hyperparathyroidism. Therefore, in a mild to moderate PTH-dependent
      hypercalcemia we must perform a family study and determine the urinary excretion
      of calcium. The presence of any other affected family member or reduced urinary
      calcium excretion is enough to suspect FHH, and this should be confirmed by the
      mutational analysis of the CASR gene, in order to establish the correct
      diagnosis, differentiated from primary hyperparathyroidism, to avoid unnecessary
      investigations or operations.

PMID- 21185799
TI  - Swedish population data and concordance for the kits PowerPlex(r) ESX 16 System,
      PowerPlex(r) ESI 16 System, AmpFlSTR(r) NGMTM, AmpFlSTR(r) SGM PlusTM and
      Investigator ESSplex.

PMID- 21185798
TI  - Diabetes prevention: can insulin secretagogues do the job?
AB  - The recent Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes
      Research (NAVIGATOR) trial reported that nateglinide, a non-sulfonylurea insulin
      secretagogue, failed to prevent progression from impaired glucose tolerance to
      diabetes. In order to determine the beneficial effect of insulin secretagogues as
      a class in diabetes prevention, we performed a literature search for randomized
      controlled studies and review articles on diabetes prevention and use of
      sulfonylureas, nateglinide, and meglitinide in PubMed and Ovid Medline since
      1950. Three studies were identified with none of them reporting success in
      preventing diabetes, indicating that insulin secretagogues should not be
      recommended for diabetes prevention.

PMID- 21185796
TI  - Liver Match, a prospective observational cohort study on liver transplantation in
      Italy: study design and current practice of donor-recipient matching.
AB  - BACKGROUND: The Liver Match is an observational cohort study that prospectively
      enrolled liver transplantations performed at 20 out of 21 Italian Transplant
      Centres between June 2007 and May 2009. Aim of the study is to investigate the
      impact of donor/recipient matching on outcomes. In this report we describe the
      study methodology and provide a cross-sectional description of donor and
      recipient characteristics and of graft allocation. METHODS: Adult primary
      transplants performed with deceased heart-beating donors were included. Relevant
      information on donors and recipients, organ procurement and allocation were
      prospectively entered in an ad hoc database within the National Transplant Centre
      web-based Network. Data were blindly analysed by an independent Biostatistical
      Board. RESULTS: The study enrolled 1530 donor/recipient matches. Median donor age
      was 56 years. Female donors (n = 681, median 58, range 12-92 years) were older
      than males (n = 849, median 53, range 2-97 years, p < 0.0001). Donors older than
      60 years were 42.2%, including 4.2% octogenarians. Brain death was due to non
      traumatic causes in 1126 (73.6%) cases. Half of the donor population was
      overweight, 10.1% was obese and 7.6% diabetic. Hepatitis B core antibody (HBcAb)
      was present in 245 (16.0%) donors. The median Donor Risk Index (DRI) was 1.57
      (>1.7 in 35.8%). The median cold ischaemia time was 7.3h (>= 10 in 10.6%). Median
      age of recipients was 54 years, and 77.7% were males. Hepatocellular carcinoma
      (HCC) was the most frequent indication overall (44.4%), being a coindication in
      roughly 1/3 of cases, followed by viral cirrhosis without HCC (28.2%) and
      alcoholic cirrhosis without HCC (10.2%). Hepatitis C virus infection (with or
      without HCC) was the most frequent etiologic factor (45.9% of the whole
      population and 71.4% of viral-related cirrhosis), yet hepatitis B virus infection
      accounted for 28.6% of viral-related cirrhosis, and HBcAb positivity was found in
      49.7% of recipients. The median Model for End Stage Liver Disease (MELD) at
      transplant was 12 in patients with HCC and 18 in those without. Multivariate
      analysis showed a slight but significant inverse association between DRI and MELD
      at transplant. CONCLUSIONS: The deceased donor population in Italy has a high
      risk profile compared to other countries, mainly due to older donor age. Almost
      half of the grafts are transplanted in recipients with HCC. Higher risk donors
      tend to be preferentially allocated to recipients with HCC, who are usually less
      ill and older. No other relevant allocation strategy is currently adopted at
      national level.

PMID- 21185800
TI  - Kinetic and stoichiometric analysis of the modification process for N-terminal
      PEGylation of staphylokinase.
AB  - Staphylokinase (SAK) is a therapeutic protein with promise for thrombolytic
      therapy of acute myocardial infarction. In this study, polyethylene glycol (PEG)
      aldehyde was used for N-terminal PEGylation of SAK to improve the pharmacological
      profiles of SAK. Due to the presence of the competitive PEGylation between the N
      terminus and the Lys residues, kinetic and stoichiometric analysis was carried
      out to investigate the process for the N-terminal PEGylation of SAK. To achieve
      this objective, size exclusion chromatography and tryptic peptide mapping were
      used to measure the PEGylation extent of SAK molecule and its specific amino acid
      residues, respectively.

PMID- 21185801
TI  - Strategy for fluorescent labeling of human acidic fibroblast growth factor
      without impairment of mitogenic activity: a bona fide tracer.
AB  - Here we describe, for the first time, the design and characterization of a bona
      fide fluorescently labeled mutant of the human acidic fibroblast growth factor
      (aFGF). The aFGF-Cys2 mutant was recombinantly synthesized by substituting the
      second amino acid with a reactive cysteine whose sulfhydryl group's side chain
      reactivity facilitated the covalent binding of a fluorescent probe as a thiolyte
      monobromobimane. Using a combination of biophysical and functional assays, we
      found that the fluorescently labeled mutant aFGF is characterized by essentially
      the same global folding, mitogenic activity, and association behavior with
      heparin, its physiological activator, as the unlabeled wild-type protein. We used
      this new tracer protein mutant to determine the association behavior of aFGF with
      heparin in the presence of high concentrations of albumin that mimicked more
      closely the plasma medium in which aFGF is naturally located and in which it has
      evolved to function. By exposing the aFGF-Cys2-heparin complex to increasing
      concentrations of albumin up to physiological plasma levels, we were able to
      demonstrate that macromolecular crowding does not affect the stoichiometry of the
      interaction. In summary, the dimeric aFGF-Cys2-heparin complex might represent a
      biologically relevant complex in physiological media.

PMID- 21185802
TI  - A modified protocol to prepare seed-free starting solutions of amyloid-beta
      (Abeta)1-40 and Abeta1-42 from the corresponding depsipeptides.
AB  - Preparing reliable, seed-free stock solutions of the highly amyloidogenic
      peptides amyloid-beta (Abeta) is difficult. Besides the formation of aggregates
      during synthesis and storage, dissolution of the peptide is a critical step
      because vortexing can induce aggregation. To overcome this, synthesis of the more
      water-soluble depsi-Abeta(1-42) peptide, from which the native sequence is easily
      obtained, has been suggested. We further refined this technique, including a
      cutoff filtration step and switching the depsipeptide in basic conditions, to
      stabilize the formed native peptide. The obtained solutions of native Abeta(1-40)
      and Abeta(1-42) peptides were homogeneous and aggregate free, as indicated by
      thioflavin T and circular dichroism analysis.

PMID- 21185803
TI  - Whole gene amplification and protein separation from a few cells.
AB  - Despite the growing interest to explore untapped microbial gene and protein
      diversity, no single platform has been able to acquire both gene and protein
      information from just a few cells. We present a microfluidic system that
      simultaneously performs on-chip capillary electrophoresis for protein analysis
      and whole genome amplification (WGA), and we demonstrate this by doing both for
      the same cohort of cyanobacterial cells. This technology opens avenues for
      studying protein profiles of precious environmental microbial samples and
      simultaneously accessing genomic information based on WGA.

PMID- 21185804
TI  - Deuteration of Escherichia coli enzyme I(Ntr) alters its stability.
AB  - Enzyme I(Ntr) is the first protein in the nitrogen phosphotransferase pathway.
      Using an array of biochemical and biophysical tools, we characterized the
      protein, compared its properties to that of EI of the carbohydrate PTS and, in
      addition, examined the effect of substitution of all nonexchangeable protons by
      deuterium (perdeuteration) on the properties of EI(Ntr). Notably, we find that
      the catalytic function (autophosphorylation and phosphotransfer to NPr) remains
      unperturbed while its stability is modulated by deuteration. In particular, the
      deuterated form exhibits a reduction of approximately 4 degrees C in thermal
      stability, enhanced oligomerization propensity, as well as increased sensitivity
      to proteolysis in vitro. We investigated tertiary, secondary, and local
      structural changes, both in the absence and presence of PEP, using near- and far
      UV circular dichroism and Trp fluorescence spectroscopy. Our data demonstrate
      that the aromatic residues are particularly sensitive probes for detecting
      effects of deuteration with an enhanced quantum yield upon PEP binding and
      apparent decreases in tertiary contacts for Tyr and Trp side chains. Trp
      mutagenesis studies showed that the region around Trp522 responds to binding of
      both PEP and NPr. The significance of these results in the context of structural
      analysis of EI(Ntr) are evaluated.

PMID- 21185806
TI  - Influence of liposome composition and membrane binding on protein kinase activity
      of PI3Kgamma.
AB  - Phosphoinositide 3-kinase gamma (PI3Kgamma) has been implicated in a variety of
      cellular signaling processes. It is a multifunctional enzyme with lipid and
      protein kinase activity that also acts as a scaffold protein. Although it is well
      known that membrane recruitment is essential for the phosphorylation of
      phosphoinositides, the cellular localization of PI3Kgamma as a protein kinase
      remains unclear. It has merely been described that PI3Kgamma protein kinase
      activity leading to MAPK activation seems to be restricted to a cytosolic
      localization. Here, we demonstrate that a hybrid-PI3Kgamma having protein kinase,
      but not lipid kinase activity shows a similar cellular distribution with a high
      membrane association and comparable liposome binding behavior to wild-type
      PI3Kgamma. Binding of PI3Kgamma to liposomes mimicking the natural plasma
      membrane slightly stimulates autophosphorylation of PI3Kgamma. However, liposomes
      containing an unphysiologically high amount of PI inhibit autophosphorylation of
      PI3Kgamma. Finally, PI3Kgamma bound to membrane fragments does not show
      autophosphorylation which is possibly due to protein-protein-interactions at the
      plasma membrane. This indicates that not only MAPK activation, but PI3Kgamma
      protein kinase activity in general is localized in the cytosol.

PMID- 21185805
TI  - Harmine is an ATP-competitive inhibitor for dual-specificity tyrosine
      phosphorylation-regulated kinase 1A (Dyrk1A).
AB  - Harmine is a beta-carboline alkaloid. The compound is a potent inhibitor of dual
      specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A), a kinase
      implicated in Down syndrome. In this study, we show that harmine functions as an
      ATP-competitive inhibitor against Dyrk1A. Our conclusion is supported by kinetic
      analysis of harmine inhibition as well as by the characterization of a Dyrk1A
      mutation conferring significant resistance to harmine. The mutation, V306A, is
      located next to the highly conserved D307 residue in kinases known to coordinate
      the phosphate groups of ATP through a Mg2+ ion. The V306A mutation offers harmine
      resistance by differentially altering Dyrk1A affinity for harmine and ATP. The
      V306A mutation causes no apparent alteration to Dyrk1A activity except for the
      reduction in ATP affinity. This deficiency could be fully compensated by
      supplying ATP with a concentration in the physiological range. Our results reveal
      that harmine inhibits Dyrk1A activity by interacting with residues in the ATP
      binding pocket and displacing ATP. Our results also suggest that harmine will be
      a good lead compound for further designing of selective ATP-competitive Dyrk1A
      inhibitors through exploration of the ATP-binding pocket of Dyrk1A.

PMID- 21185807
TI  - FOXO1 stimulates ceruloplasmin promoter activity in human hepatoma cells treated
      with IL-6.
AB  - FOXO1, a member of the winged-helix family of transcription factors, is a
      ubiquitously expressed protein involved in regulating a variety of cellular
      processes including glucose homeostasis, apoptosis, cell cycle control, muscle
      differentiation, and angiogenesis. In addition to these biological functions,
      FOXO1 is a key player in the oxidative stress response by stimulating the
      expression of metal-containing anti-oxidant proteins such as manganese superoxide
      dismutase, selenoprotein P, and catalase. Evidence in the literature suggests
      that FOXO1 may also be capable of regulating the expression of the anti-oxidant
      protein Ceruloplasmin (Cp), a six-copper-containing protein synthesized and
      secreted mainly by the liver. In the present report, we demonstrate that FOXO1
      stimulates Cp promoter activity in conjunction with the cytokine IL-6. Through
      deletional analysis and in vitro binding studies, we determine the DNA sequence
      responsible for the FOXO1-dependent regulation of the Cp proximal promoter.
      Finally, we demonstrate that FOXO1 is capable of enhancing the expression of
      endogenous Cp in human hepatic carcinoma cells treated with IL-6. These results
      allow us to identify FOXO1 as a regulator of Cp expression to promote the anti
      oxidant pathway in response to IL-6 signaling.

PMID- 21185808
TI  - Bj-PRO-5a, a natural angiotensin-converting enzyme inhibitor, promotes
      vasodilatation mediated by both bradykinin B2and M1 muscarinic acetylcholine
      receptors.
AB  - Bradykinin-potentiating peptides (BPPs) or proline-rich oligopeptides (PROs)
      isolated from the venom glands of Bothrops jararaca (Bj) were the first natural
      inhibitors of the angiotensin-converting enzyme (ACE) described. Bj-PRO-5a
      (<EKWAP), a member of this structurally related peptide family, was essential for
      the development of captopril, the first site-directed ACE inhibitor used for the
      treatment of human hypertension. Nowadays, more Bj-PROs have been identified with
      higher ACE inhibition potency compared to Bj-PRO-5a. However, despite its modest
      inhibitory effect of ACE inhibition, Bj-PRO-5a reveals strong bradykinin
      potentiating activity, suggesting the participation of other mechanisms for this
      peptide. In the present study, we have shown that Bj-PRO-5a induced nitric oxide
      (NO) production depended on muscarinic acetylcholine receptor M1 subtype (mAchR
      M1) and bradykinin B2 receptor activation, as measured by a chemiluminescence
      assay using a NO analyzer. Intravital microscopy based on transillumination of
      mice cremaster muscle also showed that both bradykinin B2 receptor and mAchR-M1
      contributed to the vasodilatation induced by Bj-PRO-5a. Moreover, Bj-PRO-5a
      mediated vasodilatation was completely blocked in the presence of a NO synthase
      inhibitor. The importance of this work lies in the definition of novel targets
      for Bj-PRO-5a in addition to ACE, the structural model for captopril development.

PMID- 21185809
TI  - Gene expression associated with an enriched environment after transient focal
      ischemia.
AB  - Recent studies have demonstrated that animals housed in an enriched environment
      after an experimental stroke obtained a better functional outcome than those
      housed in a standard cage; however, little is known about the gene expression
      associated with this functional recovery. The purpose of the present study was to
      elucidate the expression of genes in an enriched environment after experimental
      stroke in the ischemic and non-ischemic sides of the cortices. Transient focal
      brain ischemia was produced by the occlusion of the right middle cerebral artery
      (t-MCAO) in male Sprague-Dawley rats. The rats were divided into 3 groups:
      ischemic rats housed in the enriched environment, ischemic rats housed in
      standard cages, and non-ischemic rats in standard cages. Four weeks after t-MCAO,
      the rats were sacrificed and gene expression was examined. Motor function was
      improved in ischemic rats housed in the enriched environment compared with those
      in standard cages; however, there were no significant differences in the size of
      the infarct area between the ischemic rats in the enriched environment and those
      in standard cages. Decreases in the expression of Egr-1, -2, and BDNF mRNA in
      both sides of the cortices were detected in rats housed in the enriched
      environment, indicating that gene expression was altered throughout the brain at
      4 weeks after transient focal ischemia.

PMID- 21185810
TI  - The effect of disease associated point mutations on 5beta-reductase (AKR1D1)
      enzyme function.
AB  - The stereospecific 5beta-reduction of Delta(4)-3-ketosterols is very difficult to
      achieve chemically and introduces a 90 degrees  bend between ring A and B of the
      planar steroid. In mammals, the reaction is catalyzed by steroid 5beta-reductase,
      a member of the aldo-keto reductase (AKR) family. The human enzyme, AKR1D1, plays
      an essential role in bile-acid biosynthesis since the 5beta-configuration is
      required for the emulsifying properties of bile. Deficient 5beta-reductase
      activity can lead to cholestasis and neo-natal liver failure and is often lethal
      if it remains untreated. In five patients with 5beta-reductase deficiency,
      sequencing revealed individual, non-synonymous point mutations in the AKR1D1
      gene: L106F, P133R, G223E, P198L and R261C. However, mapping these mutations to
      the AKR1D1 crystal structure failed to reveal any obvious involvement in
      substrate or cofactor binding or catalytic mechanism, and it remained unclear
      whether these mutations could be causal for the observed disease. We analyzed the
      positions of the reported mutations and found that they reside in highly
      conserved portions of AKR1D1 and hypothesized that they would likely lead to
      changes in protein folding, and hence enzyme activity. Attempts to purify the
      mutant enzymes for further characterization by over-expression in Escherichia
      coli yielded sufficient amounts of only one mutant (P133R). This enzyme exhibited
      reduced K(m) and k(cat) values with the bile acid intermediate Delta(4)-cholesten
      7alpha-ol-3-one as substrate reminiscent of uncompetitive inhibition. In
      addition, P133R displayed no change in cofactor affinity but was more
      thermolabile as judged by CD-spectroscopy. When all AKR1D1 mutants were expressed
      in HEK 293 cells, protein expression levels and enzyme activity were dramatically
      reduced. Furthermore, cycloheximide treatment revealed decreased stability of
      several of the mutants compared to wild type. Our data show, that all five
      mutations identified in patients with functional bile acid deficiency strongly
      affected AKR1D1 enzyme functionality and therefore may be causal for this
      disease.

PMID- 21185811
TI  - Human antiquitin: structural and functional studies.
AB  - Antiquitin (ALDH7) is a member of the aldehyde dehydrogenase superfamily which
      oxidizes various aldehydes to form the corresponding carboxylic acids. Human
      antiquitin (ALDH7A1) is believed to play a role in detoxification, osmoregulation
      and more specifically, in lysine metabolism in which alpha-aminoadipic
      semialdehyde is identified as the specific, physiological substrate of the
      enzyme. In the present study, the structural basis for the substrate specificity
      was studied by site-directed mutagenesis. Kinetic analysis on wild-type human
      antiquitin and its mutants E121A and R301A demonstrated the importance of Glu121
      and Arg301 in the binding as well as the turnover of alpha-aminoadipic
      semialdehyde. On the functional aspect, in addition to the already diversified
      physiological functions of antiquitin, the recent demonstration of its presence
      in the nucleus suggests that it may also play a role in cell growth and cell
      cycle progression. In this investigation, the expression level of antiquitin was
      monitored in synchronized WRL68 and HEK293 cell culture systems. It was found
      that the protein was up-regulated during G(1)-S phase transition.
      Immunofluorescence staining of the synchronized cells demonstrated an increased
      expression and accumulation of antiquitin in the nucleus during the G(1)-S phase
      transition. Knockdown of antiquitin using shRNA transfection also resulted in
      changes in the levels of several key cell cycle-regulating proteins.

PMID- 21185812
TI  - Characterization of the steroid degrading bacterium S19-1 from the Baltic Sea at
      Kiel, Germany.
AB  - Steroid contamination of sea water is an ever growing problem and impacts
      population dynamics of all kinds of sea animals. We have long experience with the
      soil bacterium Comamonas testosteroni ATCC11996 which is able to catabolize a
      variety of steroids and polycyclic aromatic hydrocarbons, and which might be used
      in the bioremediation of contaminated places. In C. testosteroni about 20 enzymes
      which are involved in steroid degradation could be induced by 0.5 mM
      testosterone. In this work, we isolated a marine bacterial strain, S19-1, from
      the Baltic Sea at Kiel (Germany) which degrades steroids and is able to use
      steroids as carbon source. S19-1 was characterized as being Gram negative, and
      16S rRNA analysis showed that it belongs to the genus Buttiauxella of the
      Enterobacteriaceae family. Strain S19-1 could be best grown in SIN medium
      supplemented with 0.6-4.1% NaCl at 20 degrees C. As a carbon source,
      testosterone, estradiol or cholesterol in minimal medium could be used by S19-1.
      Moreover, S19-1 could grow up in medium with 50 MUg/ml erythromycin. Plasmids
      pK18 and other plasmids were successfully transformed into S19-1 by chemical
      transformation (CaCl(2)) and shown to replicate in the cells. Currently, work is
      ongoing to find the steroid inducible genes.

PMID- 21185813
TI  - Effect of membrane composition on lipid oxidation in liposomes.
AB  - To study the effect of membrane composition on the oxidation of liposomes,
      different systems were prepared by adding one component at time to
      phosphatidylcholine (Epikuron 200). In particular, the effect of cholesterol and
      its ester, cholesterol stearate, on membrane structure and oxidation was studied.
      A first screening of the structure and net charge of the different preparation
      was made by means of z-potential and size measurements. Then the liposomes were
      oxidized by using a hydrophilic radical initiator, the (2,2-azobis(2
      amidinopropane) hydrochloride, AAPH, which thermally decomposes to give a
      constant radical flux in water. The oxidation of liposomes, monitored by
      following the absorbance of the primary products of oxidation at 234 nm, was
      shown to be dependent on the composition of the liposomal bilayer and so on its
      biophysical properties. In addition, size and z-potential measurements gathered
      in the time course of the peroxidation reaction, revealed that the oxidation
      induced a modification of the superficial characteristics of the membrane bilayer
      so as to change its charge at the shear plane (z-potential). This behaviour was
      shared by all liposomal preparations independent of the composition. The change
      in sizes of the different liposomal preparation, instead, followed different
      trends, being more stable both in control samples and in oxidized ones when
      cholesterol was present. From the analysis of the results, it can be concluded
      that cholesterol affects the oxidation induced by hydrophilic radical initiator
      of model membranes by changing the biophysical properties of the phospholipid
      bilayer. The rigidity induced by cholesterol at temperatures above the T(m) makes
      the membrane more resistant to radical attack from an external aqueous phase and
      this in turn delays the start of the reaction. The decrease of z-potential of the
      liposomal particles induced by the oxidation process can be an important clue to
      understand the mechanisms involved in the etiology of important diseases.

PMID- 21185814
TI  - Preparation of submicron liposomes exhibiting efficient entrapment of drugs by
      freeze-drying water-in-oil emulsions.
AB  - A novel liposome preparation method is described as freeze-drying of water-in-oil
      emulsions containing sucrose in the aqueous phase (W) and phospholipids and
      poly(ethylene glycol)(1500) (PEG) in the oil phase (O). The water-in-oil
      emulsions were prepared by sonication and then lyophilized to obtain dry
      products. Upon rehydration, the dry products formed liposomes with a size smaller
      than 200 nm and an encapsulation efficiency (EE) higher than 60% for model drugs.
      The presence of lyoprotectant and PEG was found to be a prerequisite for the
      formation of liposomes with desirable properties, such as a small particle size
      and high EE. The lyophilates were stable and could be rehydrated to form
      liposomes without any change in size or EE even after a storage period of 6
      months. Also, the lipophilic drug-containing FWE liposomes were stable and could
      be stored for at least 6 months although the liposomes containing hydrophilic
      drugs showed significant leakage. Based on the vesicle size and EEs of the model
      drugs, as well as the scanning electron micrograph (SEM) and small angle X-ray
      scattering (SAXS) pattern of the lyophilates, a possible mechanism for the
      liposome formation is proposed.

PMID- 21185815
TI  - Role of hydrophobic and polar interactions for BSA-amphiphile composites.
AB  - To evaluate the role of hydrophobic and electrostatic or other polar interactions
      for protein-ligand binding, we have studied the interactions of bovine serum
      albumin (BSA) with 2-alkylmalonic acid and 2-alkylbenzimidazole amphiphiles
      having different head group and alkyl chain length. The binding affinity for the
      protein-amphiphile interactions is found to depend predominantly on the length of
      hydrocarbon chain, suggesting the crucial role of hydrophobic forces, supported
      by polar interactions at the protein surface. The BSA fluorescence exhibits
      appreciable hypsochromic shift along with a reduction in fluorescence intensity
      and mean lifetime upon binding with 2-alkylmalonic acid. UV-visible, steady state
      and time-resolved fluorescence measurements were performed to compare the effects
      of amphiphiles on BSA as a function of the amphiphiles head group and alkyl chain
      length.

PMID- 21185816
TI  - Lipid bilayer molecular dynamics study of lipid-derived agonists of the putative
      cannabinoid receptor, GPR55.
AB  - Both L-alpha-lysophosphatidylinositol (LPI) and 2-arachidonoyl-sn-glycero-3
      phosphoinositol (2-AGPI) have been reported to activate the putative cannabinoid
      receptor, GPR55. Recent microsecond time-scale molecular dynamics (MD)
      simulations and isothiocyanate covalent labeling studies have suggested that a
      transmembrane helix 6/7 (TMH6/7) lipid pathway for ligand entry may be necessary
      for interaction with cannabinoid receptors. Because LPI and 2-AGPI are lipid
      derived ligands, conformations that each assumes in the lipid bilayer are
      therefore likely important for their interaction with GPR55. We report here the
      results of 70 ns NAMD molecular dynamics (MD) simulations of LPI and of 2-AGPI in
      a fully hydrated bilayer of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine
      (POPC). These simulations are compared with a 70 ns simulation of the cannabinoid
      CB1 receptor endogenous ligand, N-arachidonoylethanolamine (anandamide, AEA) in a
      POPC bilayer. These simulations revealed that (1) LPI and 2-AGPI sit much higher
      in the bilayer than AEA, with inositol headgroups that can at times be solvated
      completely by water; (2) the behavior of the acyl chains of AEA and 2-AGPI are
      similar in their flexibilities in the bilayer, while the acyl chain of LPI has
      reduced flexibility; and (3) both 2-AGPI and LPI can adopt a tilted headgroup
      orientation by hydrogen bonding to the phospholipid phosphate/glycerol groups or
      via intramolecular hydrogen bonding. This tilted head group conformation (which
      represents over 40% of the conformer population of LPI (42.2 +/- 3.3%) and 2-AGPI
      (43.7 +/- 1.4%)) may provide a low enough profile in the lipid bilayer for LPI
      and 2-AGPI to enter GPR55 via the putative TMH6/7 entry port.

PMID- 21185817
TI  - Analytical validation of microdialysis analyzer for monitoring glucose, lactate
      and pyruvate in cerebral microdialysates.
AB  - BACKGROUND: Cerebral microdialysis is a valuable tool for neurochemical
      monitoring of acute brain injury. We performed an independent analytical
      validation of glucose, lactate and pyruvate methods on the new ISCUS(flex) new
      analyzer developed by CMA Microdialysis. METHODS: Evaluation of analytical
      parameters included limit of detection, limit of quantification, linearity, intra
      and inter-assay imprecision expressed as the coefficient of variation (CV),
      recovery, inter-sample and inter-reagent contamination, drug and bilirubin
      interferences, sample stability, method comparison. RESULTS: Linearity ranges
      were 0.1-25 mmol/L, 0.2-12 mmol/L and 19-1500 MUmol/L for glucose, lactate and
      pyruvate respectively. For critical threshold, intra- and inter-assay CVs were
      3.1/4.5% for glucose (1 mmol/L), 3.5/4% for lactate (4 mmol/L) and 3.3/4.3% for
      pyruvate (100 MUmol/L). Inter-assay CVs for lactate/pyruvate (LPR) and
      lactate/glucose (LGR) ratios were 5.9% and 6.0% respectively. For glucose,
      lactate, pyruvate, LPR and LGR, the reference change values (RCV) were 20%, 26%,
      20%, 27% and 28% respectively. Practically, variations below 27% between two
      successive LPR values could not be interpreted as significant. CONCLUSION: These
      data prove that ISCUS(flex) has the qualities required for clinical application
      in neuro-intensive care. Correct clinical interpretation of data need the
      implementation of a strict quality control program and strong cooperation between
      clinicians and biologists.

PMID- 21185818
TI  - Identification of biomarkers to improve diagnostic sensitivity of sporadic
      colorectal cancer in patients with low preoperative serum carcinoembryonic
      antigen by clinical proteomic analysis.
AB  - BACKGROUND: Colorectal cancer (CRC) is the third most common type of cancer
      worldwide. Carcinoembryonic antigen (CEA) assays usually give false negative
      results. To improve the diagnosis of primary sporadic CRC, there is an urgent
      need to identify new biomarkers. METHODS: We used laser pressure catapulting and
      proteomics to analyze overexpressed cancer associated proteins from 48 sporadic
      CRC patients with low preoperative serum CEA (LPSC) (<5 ng/ml). Real-time Q-PCR
      was used to identify the target gene transcripts. Immunoblots were carried out to
      validate the biomarkers. RESULTS: Alpha-enolase, HSP27 and macrophage migration
      inhibitory factor (MIF) were overexpressed in all tumor tissues from 48 LPSC CRC
      patients, as assessed by 2DE image analysis. The genes were also overexpressed at
      the transcript level in all tumor tissues from the same patients. In the
      immunoblot assay, only serum levels of Alpha-enolase and MIF were significantly
      overexpressed in the LPSC group compared to the mean levels in the control group.
      Combined with the determinations of preoperative CEA levels, screening for serum
      Alpha-enolase and MIF were shown to improve the diagnosis of primary CRC.
      CONCLUSIONS: Serum Alpha-enolase and MIF may be potential biomarkers that can be
      used to improve clinical predication of primary CRC with LPSC.

PMID- 21185819
TI  - Biomarker discovery in biological specimens (plasma, hair, liver and kidney) of
      diabetic mice based upon metabolite profiling using ultra-performance liquid
      chromatography with electrospray ionization time-of-flight mass spectrometry.
AB  - BACKGROUND: The number of diabetic patients has recently been increasing
      worldwide. Diabetes is a multifactorial disorder based on environmental factors
      and genetic background. In many cases, diabetes is asymptomatic for a long period
      and the patient is not aware of the disease. Therefore, the potential
      biomarker(s), leading to the early detection and/or prevention of diabetes
      mellitus, are strongly required. However, the diagnosis of the prediabetic state
      in humans is a very difficult issue, because the lifestyle is variable in each
      person. Although the development of a diagnosis method in humans is the goal of
      our research, the extraction and structural identification of biomarker
      candidates in several biological specimens (i.e., plasma, hair, liver and kidney)
      of ddY strain mice, which undergo naturally occurring diabetes along with aging,
      were carried out based upon a metabolite profiling study. METHODS: The low
      molecular-mass compounds including metabolites in the biological specimens of
      diabetic mice (ddY-H) and normal mice (ddY-L) were globally separated by ultra
      performance liquid chromatography (UPLC) using different reversed-phase columns
      (i.e., T3-C18 and HS-F5) and detected by electrospray ionization time-of-flight
      mass spectrometry (ESI-TOF-MS). The biomarker candidates related to diabetes
      mellitus were extracted from a multivariate statistical analysis, such as an
      orthogonal partial least-squares-discriminant analysis (OPLS-DA), followed by a
      database search, such as ChemSpider, KEGG and HMDB. RESULTS: Many metabolites and
      unknown compounds in each biological specimen were detected as the biomarker
      candidates related to diabetic mellitus. Among them, the elucidation of the
      chemical structures of several possible metabolites, including more than two
      biological specimens, was carried out along with the comparison of the tandem
      MS/MS analyses using authentic compounds. One metabolite was clearly identified
      as N-acetyl-L-leucine based upon the MS/MS spectra and the retention time on the
      chromatograms. CONCLUSIONS: N-acetyl-L-leucine is an endogenous compound included
      in all biological specimens (plasma, hair, liver and kidney). Therefore, this
      metabolite appears to be a potential biomarker candidate related to diabetes.
      Although the structures of other biomarker candidates have still not yet
      determined, the present approach based upon a metabolite profiling study using
      UPLC-ESI-TOF-MS could be helpful for understanding the abnormal state of various
      diseases.

PMID- 21185820
TI  - APOC3 -482C>T polymorphism, circulating apolipoprotein C-III and smoking:
      interrelation and roles in predicting type-2 diabetes and coronary disease.
AB  - OBJECTIVES: We determined the relationship of smoking status on APOC3 -482C>T
      polymorphism and apolipoprotein C-III (apoC-III) concentrations and the latter
      two parameters' influence on risk of diabetes and coronary heart disease (CHD).
      DESIGN AND METHODS: Prediction of incident cases was assessed at 5.5years' follow
      up in unselected 519 individuals of a general population genotyped for -482C>T
      polymorphism. RESULTS: Female sex and current smoking were significantly
      associated with low circulating apoC-III in subjects without (p<=0.033) than with
      abdominal obesity (p=0.053) or than insulin resistant -482TT homozygotes
      (p=0.034) who had 20-30% higher serum apoC-III. Multi-adjusted serum apoC-III was
      log-linearly associated with fasting triglycerides. ApoC-III levels determined
      the development of diabetes [RR 1.56 (95%CI 1.21; 2.01)] and CHD [RR 1.38 (1.10;
      1.72) for an increment of 14%], after adjustment for confounders. CONCLUSION:
      APOC3 -482TT genotype is associated with high apoC-III concentrations only in the
      presence of abdominal obesity or insulin resistance, but not in current smokers
      who remain lean or insulin-sensitive. Rather than APOC3 -482C>T polymorphism,
      circulating apoC-III determines cardiometabolic risk.

PMID- 21185821
TI  - Antagonism of 5-HT(2A) receptors inhibits the expression of pronociceptive
      mediator and enhances endogenous opioid mechanism in carrageenan-induced
      inflammation in rats.
AB  - We have recently reported that treatment with the 5-HT(2A) receptor antagonist
      ketanserin in the inflamed paw raises the nociceptive threshold above normal
      level (hypoalgesia) and this response is naloxone-reversible. The present study
      aimed to investigate neurochemical changes at the site of inflammation and in
      dorsal root ganglia (DRG) and the spinal cord following the blockade of 5-HT(2A)
      receptors. Intraplantar injection of ketanserin (20 MUg) inhibited carrageenan
      induced increase in CGRP immunoreactivity-positive neurons in DRG. On the other
      hand, administration of ketanserin (20 MUg) and 5-HT (10 MUg), but not vehicle,
      enhanced and inhibited recruitment of beta-endorphin-expressing immune cells,
      respectively, in subcutaneous loci of inflamed hindpaw. Moreover, the treatment
      with ketanserin increased the number of endomorphine-containing cells in the
      inflamed paw and MU-opioid receptor-expressing neurons in DRG at L4-5 but reduced
      the expression of endomorphine in superficial layers of the lumbar spinal cord.
      The present study provided evidence at the cellular level showing that the
      blockade of 5-HT(2A) receptors inhibited inflammation-associated increase in
      pronociceptive mediator, and that the pronociceptive property of 5-HT is mediated
      by the suppression of inflammation-activated opioid mechanism. Therefore,
      targeting the 5-HT(2A) receptors in the site of inflammation may be a promising
      approach to inhibit inflammatory pain.

PMID- 21185822
TI  - Sodium hydrosulfide improves the protective potential of the cardioplegic
      histidine buffer solution.
AB  - Since H(2)S has an emerging role as a cardioprotector, we hypothesized that NaHS
      addition to the new cardioplegic histidine buffer solution (HBS) could improve
      its cardioprotective potential. Male Wistar-Han rat hearts were divided in 4
      groups: i) control, ii) perfusion control (perfusion only), iii) 6h ischemia in
      HBS or in a modified-HBS with 100 MUM of NaHS, a H(2)S donor, (HBSM) and iv) as
      iii followed by 30 min reperfusion. During ischemia, aliquots of the cardioplegic
      solution were collected for NMR analysis. Heart mitochondria respiration and
      transmembrane potential were measured after ischemia or after ischemia followed
      by reperfusion. Proteins involved in the apoptotic signaling pathway were also
      quantified in both mitochondrial and tissue samples. Cardiac mechanic performance
      was evaluated by measuring the heart rate and the left ventricular pressure. In
      HBSM-preserved hearts, a) glucose consumption increased as well as lactate and
      alanine production during ischemia, b) heart mitochondria presented an improved
      phosphorylative efficiency, including decreased phosphorylative lag phase for
      complex I and complex II substrates, c) mitochondrial and tissue p53, Bax and
      caspase-9 were lower and d) there was a more positive atrial chronotropic
      response than in HBS-preserved hearts. We concluded that the addition of NaHS to
      HBS enhances glycolysis during ischemia, decreases mitochondrial dysfunction,
      especially by preserving the phosphorylative system, prevents apoptosis and
      during ischemia/reperfusion.

PMID- 21185823
TI  - Role of prostanoid IP and EP receptors in mediating vasorelaxant responses to
      PGI2 analogues in rat tail artery: Evidence for Gi/o modulation via EP3
      receptors.
AB  - Prostanoid IP receptors coupled to Gs are thought to be the primary target for
      prostacyclin (PGI(2)) analogues. However, these agents also activate prostanoid
      EP(1-4) receptor subtypes to varying degrees, which are positively (EP(2/4)) or
      negatively (EP(3)) coupled to adenylate cyclase through Gs or Gi, respectively.
      We investigated the role of these receptors in modulating relaxation to PGI(2)
      analogues cicaprost, iloprost and treprostinil in pre-contracted segments of rat
      tail artery. Prostanoid IP (RO1138452), EP(4) (GW627368X), EP(3) (L-798106), EP(1
      3) (AH6809), and EP(1) (SC-51322) receptor antagonists were used to determine
      each receptor contribution. The role of G(i/o) was investigated using pertussis
      toxin (PTX), while dependence on cAMP was determined using adenylate cyclase
      (2'5'dideoxyadenosine, DDA) and protein kinase A (2'-O-monobutyryladenosine-
      3',5'-cyclic monophosphorothioate, Rp- isomer, Rp-2'-O-MB-cAMPS) inhibitors, and
      by measurement of tissue cAMP. All analogues caused relaxation which was
      significantly (P<0.01) inhibited by RO1138452; with maximum response to
      cicaprost, iloprost and treprostinil reduced by 51%, 66% and 37%, respectively.
      GW627368X had no effect when used alone, but in combination with RO1138452,
      caused a rightward shift of the curves for cicaprost and iloprost but not
      treprostinil. PTX treatment potentiated relaxation to all 3 analogues (P<0.01),
      as did L798106 and AH6809 but not SC-51322. Basal cAMP levels were higher in PTX
      treated tissues and DDA- and Rp-2'-O-MB-cAMPs--sensitive responses increased to
      analogue concentrations <0.1MUM. In conclusion, prostanoid EP(3) receptors via
      G(i/o) negatively modulate prostanoid IP receptor-mediated relaxation to
      cicaprost, iloprost and treprostinil. However, other pathways contribute to
      analogue-induced vasorelaxation, the nature of which remains unclear for
      treprostinil.

PMID- 21185824
TI  - Pharmacological treatment of hyperinsulineamia in rats depends on coping style.
AB  - Passive and proactive coping styles are associated with marked differences in
      behavioral and neuroendocrine responses. Previous studies revealed that the
      passive individuals are more prone to hyperinsulinemia. Likewise, we hypothesize
      that different coping styles may require different drugs to treat this. We tested
      this by treating passive and proactive rats (Roman Low Avoidance and Roman High
      Avoidance rats respectively) with either Rosiglitazone or with RU486. After eight
      days of treatment we performed and intravenous glucose tolerance test (IVGTT) and
      we compared the insulin and glucose levels with those measured during the IVGTT
      at baseline. Rosiglitazone improved insulin levels during an IVGTT in both
      passive and proactive coping styles. RU486, however, lowered insulin levels only
      in rats with a passive coping style. This study suggests that insight in the
      neuroendocrine differences between passive and proactive coping styles may
      provide an extra impulse to improve treatment of insulin resistance, since it
      allows the application of drugs targeted at the individual.

PMID- 21185825
TI  - Zinc protects against indomethacin-induced damage in the rat small intestine.
AB  - The clinical utility of nonsteroidal anti-inflammatory drugs (NSAIDs) is often
      limited by the adverse effects that they produce in the small intestine.
      Alterations in the composition and functions of the glycocalyx and brush border
      membranes of the rat small intestine have been shown to occur in response to
      indomethacin, an NSAID often used in the study of adverse effects of these drugs.
      The micronutrient, zinc, has been documented to have cytoprotective effects in
      the gastrointestinal tract. The aim of this study was to evaluate the potential
      of zinc to reduce indomethacin-induced small intestinal damage. We pre-treated
      rats with zinc sulphate (50 mg/kg body weight) 2h before administration of
      indomethacin (20 mg/kg body weight) and sacrificed the rats 1, 12 or 24h after
      indomethacin. The extent of small intestinal mucosal damage and the content of
      lipids and sugars in the mucosa were determined. Bacterial counts in the
      intestinal lumen and the mucosa were ascertained. Activities of matrix
      metalloproteinases (MMPs) and levels of metallothionein in the mucosa were also
      measured. Pre-treatment with zinc sulphate was found to reduce the extent of
      indomethacin-induced mucosal damage. It also prevented drug-induced changes in
      the content of lipids and sugars in the mucosa. Drug-induced increases in
      activities of the MMPs and bacterial counts in the intestine were also attenuated
      by zinc. Metallothionein levels were significantly higher in animals pre-treated
      with zinc. We conclude that zinc was effective in protecting against indomethacin
      induced small intestinal damage and suggest that it may do so by induction of
      metallothionein.

PMID- 21185826
TI  - Chronic peripheral administration of somatostatin receptor subtype-4 agonist NNC
      26-9100 enhances learning and memory in SAMP8 mice.
AB  - Selective somatostatin receptor subtype agonists have been proposed as a means to
      mitigate learning and memory loss associated with Alzheimer's disease. The first
      aim of this study evaluated blood-to-brain transport and regional brain
      distribution of NNC 26-9100, a selective somatostatin subtype-4 (sst4) receptor
      agonist. The entry rate of (131)I-NNC 26-9100 was K(i)=0.25 MUl/g min, with an
      ~93% association with the parenchymal component. The second goal of this study
      was to evaluate the effect of chronic NNC 26-9100 administration (i.p.) on
      learning and memory, brain Abeta(x-42) levels, and protein expression of sst4
      receptor and amyloid precursor protein (APP) in the senescence-accelerated mouse
      p8 (SAMP8) model of Alzheimer's disease. Mice chronically treated with NNC 26
      9100 showed improved learning (day 21) and memory (day 28) using the T-maze
      paradigm (20 and 200 MUg). Ex vivo tissue analyses showed a decline in Abeta(x
      42) levels at the 20 MUg dose, while no alterations were observed in sst4
      receptor or APP protein expression compared to vehicle controls. These findings
      indicate NNC 26-9100 is taken up into key brain regions associated with learning
      and memory. Furthermore, chronic administration of NNC 26-9100 improved learning
      and memory and decreased Abeta(x-42) brain levels. These results suggest sst4
      receptor agonists may provide a viable therapy in the treatment of Alzheimer's
      disease and other forms of cognitive impairment.

PMID- 21185827
TI  - Docetaxel inhibits cyclooxygenase-2 induction in vascular smooth muscle cells.
AB  - The aim of this study was to determine whether docetaxel affects expression of
      cyclooxygenase-2 (COX-2) in vascular smooth muscle cells. Cultured rat aortic
      smooth muscle cells (RASMCs) were stimulated with interleukin-1b (IL-1beta). COX
      2 expression level and ERK activity were evaluated by Western blot analysis. COX
      2 expression as well as tubulin formation was also evaluated by
      immunocytochemical analysis. IL-1beta induced COX-2 expression in RASMCs, which
      was inhibited by docetaxel (5-20ug/ml) in a concentration-dependent manner. IL
      1beta increased ERK activity, which was not affected by docetaxel. IL-1beta
      induced COX-2 expression level was markedly augmented at 24h after washing out
      docetaxel from the culture medium. Immunocytochemical analysis revealed that COX
      2 immunoreactivity in RASMCs stimulated with IL-1beta was decreased in the
      presence of docetaxel but was recovered at 24h after washing out docetaxel, while
      docetaxel-induced change in tubulin formation, namely, polymerization of alpha
      tubulin fibers, remained at 24h after washing out docetaxel. The results suggest
      that docetaxel inhibits COX-2 induction, and this action of docetaxel is
      reversible and ERK-independent.

PMID- 21185828
TI  - Protective effect of embelin against acetic acid induced ulcerative colitis in
      rats.
AB  - The aim of the present study is to evaluate the effect of embelin isolated from
      Embelia ribes on acetic acid induced colitis in rats. Experimental animals
      received embelin (25 and 50 mg/kg, p.o.) and sulfasalazine (100mg/kg, p.o.) for
      five consecutive days before induction of colitis by intra-rectal acetic acid (3%
      v/v) administration and the treatment continued up to 7 days. The colonic mucosal
      injury was assessed by clinical, macroscopic, biochemical and histopathological
      examinations. Embelin treatment significantly decreased clinical activity score,
      gross lesion score, percent affected area and wet colon weight when compared to
      acetic acid induced controls. The treatment also reduced significantly the
      colonic myeloperoxidase activity, lipid peroxides and serum lactate dehydrogenase
      and significantly increased the reduced glutathione. The histopathological
      studies also confirmed the foregoing findings. The protective effect may be due
      to its antioxidant and anti-inflammatory activities.

PMID- 21185829
TI  - Gene expression changes in patient-matched gastric normal mucosa, adenomas, and
      carcinomas.
AB  - A subset of gastric carcinomas shows histologic evidence of a multistep process,
      progressing from gastric adenoma to gastric carcinoma. We examined gene
      expression changes during the gastric adenoma-carcinoma sequence in 26 snap
      frozen samples (normal mucosa, adenoma, and carcinoma samples from eight patients
      and two additional carcinomas) by oligonucleotide microarray. Unsupervised
      hierarchical clustering analysis demonstrated differential gene expression
      between gastric normal mucosa, adenomas and carcinomas. We identified 319 and 422
      genes differentially regulated in adenoma and carcinoma, respectively, relative
      to normal mucosa, using a combination of Welch's t-test and fold-change analysis.
      Applying a combination of robust multi-category support vector machines to the
      data, reveal that 39 and 21 genes were gradually up- and down-regulated,
      respectively, in succession in normal mucosa, adenoma, and carcinoma samples. We
      validated gene expression levels of four genes: hydroxyprostaglandin
      dehydrogenase 15 (HPGD), follistatin-like 1, trefoil factor 1 (TTF1) and trefoil
      factor 2 (TFF2) by RT-PCR and found direct correlation with microarray results.
      The expressions of the TFF2 and HPGD genes were further evaluated by
      immunohistochemistry in 103 adenomas and 70 carcinomas; expression of both
      proteins was decreased in these tissues. The progressive alteration in gene
      expression in the transition from normal mucosa to carcinoma suggests that these
      changes may play critical roles in gastric carcinogenesis.

PMID- 21185830
TI  - Discovery of two novel EWSR1/ATF1 transcripts in four chimerical transcripts
      expressing clear cell sarcoma and their quantitative evaluation.
AB  - The most common recurrent translocation in clear cell sarcoma t(12;22)(q13;q12)
      results in an EWSR1/ATF1 chimeric gene. We present a molecular analysis of tumor
      overgrowing right proximal tibia with bone destruction metastatic to two groin
      lymph nodes. Fluorescent in situ hybridization analysis performed on paraffin
      embedded tissue sections of primary tumor sample indicated one rearranged locus
      of EWSR1 gene and one additional red signal. Reverse transcription-polymerase
      chain reaction analysis revealed the presence of four different EWSR1/ATF1
      chimerical transcripts in the tumor sample as well as in both metastatic lymph
      nodes. Two previously described transcripts EWSR1exon7/ATF1exon5 and
      EWSR1exon8/ATF1exon4, and two novel transcripts EWSR1exon7/ATF1exon4 and
      EWSR1exon9/ATF1exon4 were identified. Both novel transcripts were out-of-frame
      fusions and, therefore, most likely had limited biological impact in oncogenesis
      of clear cell sarcoma. Quantitative evaluation demonstrated unequal distribution
      of these transcripts, with EWSR1exon8/ATF1exon4 type being overexpressed.

PMID- 21185832
TI  - Lack of protective effect of local administration of triamcinolone or systemic
      treatment with methylprednisolone against damages caused by optic nerve crush in
      rats.
AB  - The purpose of the present study was to investigate the effects of
      administrations of triamcinolone acetonide and systemic methylprednisolone sodium
      succinate on optic nerves (ON) and retinal ganglion cells (RGC) in a rat model of
      optic nerve crush. The treated groups either received triamcinolone immediately
      in the form of two pieces of soaked-gelform surrounding retrobulbar optic nerves
      (0.5 mg/per gelform) or methylprednisolone via peritoneal injection, and control
      group received intra-peritoneal injection with phosphate-buffered saline (PBS)
      after crush experiments. RGC density was counted by retrograde labeling with
      Fluorogold, and visual function was assessed by flash visual-evoked potentials.
      Terminal transferase dUTP nick end-labeling (TUNEL) assays, Western blot analysis
      of serine/threonine kinase (p-Akt), extracellular signal-regulated kinases (p
      ERK) and signal transducer and activator of transcription 3 (p-STAT3) and
      immunohistochemistry of ED1, marker of macrophage/microglia in the optic nerve
      were conducted. Two and four weeks after optic nerve crush experiments, neither
      triamcinolone nor methylprednisolone treatment rescued the RGC from death in the
      central and mid-peripheral retinas compared with those of the corresponding optic
      nerve-crushed and PBS-treated rats. Visual-evoked potentials measurements showed
      a prolonged latency of the P(1) wave in all treated groups (triamcinolone
      treated: 123 +/- 23 ms, methylprednisolone-treated: 133 +/- 25 ms and PBS
      treated: 151 +/- 55 ms) after two weeks. TUNEL assays showed that there was no
      decrease in apoptotic cells in the RGC layers of both triamcinolone treated and
      methylprednisolone-treated retinas. Western blot analysis showed that p-AKT, p
      ERK and p-Stat3 were not up-regulated in either retina of the triamcinolone or
      methylprednisolone treated rats. In addition, the number of ED1-positive cells
      was not attenuated at the lesion sites of the ON in either treatment group. Based
      upon these results, we conclude that neither retrobulbar administration of
      triamcinolone nor systemic administration of methylprednisolone has any
      neuroprotective effects in a rat model of optic nerve crush.

PMID- 21185831
TI  - Annexin A6 contributes to the invasiveness of breast carcinoma cells by
      influencing the organization and localization of functional focal adhesions.
AB  - The interaction of annexin A6 (AnxA6) with membrane phospholipids and either
      specific extracellular matrix (ECM) components or F-actin suggests that it may
      influence cellular processes associated with rapid plasma membrane reorganization
      such as cell adhesion and motility. Here, we examined the putative roles of AnxA6
      in adhesion-related cellular processes that contribute to breast cancer
      progression. We show that breast cancer cells secrete annexins via the exosomal
      pathway and that the secreted annexins are predominantly cell surface-associated.
      Depletion of AnxA6 in the invasive BT-549 breast cancer cells is accompanied by
      enhanced anchorage-independent cell growth but cell-cell cohesion, cell
      adhesion/spreading onto collagen type IV or fetuin-A, cell motility and
      invasiveness were strongly inhibited. To explain the loss in adhesion/motility,
      we show that vinculin-based focal adhesions in the AnxA6-depleted BT-549 cells
      are elongated and randomly distributed. These focal contacts are also
      functionally defective because the activation of focal adhesion kinase and the
      phosphoinositide-3 kinase/Akt pathway were strongly inhibited while the MAP
      kinase pathway remained constitutively active. Compared with normal human breast
      tissues, reduced AnxA6 expression in breast carcinoma tissues correlates with
      enhanced cell proliferation. Together this suggests that reduced AnxA6 expression
      contributes to breast cancer progression by promoting the loss of functional cell
      cell and/or cell-ECM contacts and anchorage-independent cell proliferation.

PMID- 21185833
TI  - Effect of hypothyroxinemia on thyroid hormone responsiveness and action during
      rat postnatal neocortical development.
AB  - Neurological deficits due to maternal and neonatal hypothyroxinemia under mild
      moderate iodine deficiency are a major preventable health problem worldwide. The
      present study assesses the impact of hypothyroxinemia on postnatal neocortical
      development and also compares it to the known effects of severe hypothyroidism.
      Our results strongly suggest that even within elevated circulating
      triiodothyronine (T3) levels, hypothyroxinemia significantly impairs thyroid
      hormone responsiveness in developing rat neocortex. The significant compensatory
      alteration in deiodinase levels with unaltered monocarboxylate transporter 8
      (MCT8) and thyroid hormone receptors (TRs), although found to be similar in
      hypothyroxinemic and hypothyroid condition, is more pronounced under later
      condition. The resultant downregulation of nuclear myelin binding protein (MBP)
      and mitochondrial transcripts Cytochrome oxidase III (Cox III) as well as
      significantly enhanced mitochondrial localization of Bax and reduced Bcl-2 and
      Bcl-xL accompanied by enhanced release of Cytochrome c and Smac with activation
      of caspase-3 indicates pronounced apoptosis leading to compromised cellular
      survival. The similarities of this responsiveness albeit with difference in
      degree under hypothyroidism and hypothyroxinemic state with adequate availability
      of T3 are suggestive of an independent role of thyroxine in neocortex
      development. Taken together, this study brings forth the neurophysiological
      aspects of hypothyroxinemia and underscores the importance of adequate iodine
      nutrition along with mandatory thyroxin monitoring during pregnancy and after
      birth.

PMID- 21185834
TI  - Chronic infusion of CDNF prevents 6-OHDA-induced deficits in a rat model of
      Parkinson's disease.
AB  - Cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived
      neurotrophic factor (MANF) constitute a novel, evolutionarily conserved family of
      neurotrophic factors (NTF) expressed in vertebrates and invertebrates. The
      effects of two-week infusions of CDNF, MANF and glial cell line-derived
      neurotrophic factor (GDNF) were studied in a rat 6-hydroxydopamine (6-OHDA)
      hemiparkinsonian model. Degeneration of nigrostriatal dopamine nerve tract after
      toxin injection was assessed by measuring amphetamine-induced rotational
      behavior, and at the end of the experiment by quantifying tyrosine hydroxylase
      (TH)-positive neurons in the substantia nigra pars compacta (SNpc) and TH
      positive fibers in the striatum. The diffusion of the NTFs into the brain tissue
      following chronic infusion was also studied. Finally, we examined the
      transportation of intrastriatally injected (125)I-CDNF within the brain. The
      amphetamine-induced rotational behavior was gradually normalized in rats treated
      with CDNF for two weeks following the intrastriatal 6-OHDA injection. CDNF was
      also able to inhibit 6-OHDA-induced loss of TH-immunoreactive cells of the SNpc
      and TH-positive fibers in the striatum. MANF and GDNF had no statistically
      significant effect in any of the above measures. The volume of distribution for
      MANF in the striatum was significantly larger than that of GDNF after 3-day
      infusions. Both (125)I-CDNF and (125)I-GDNF were retrogradely transported from
      the striatum to the SN. No behavioral signs of toxicity were observed during
      treatment with the three NTFs. These results imply that CDNF may have potential
      as a neuroprotective or even neurorestorative therapy of PD.

PMID- 21185835
TI  - Zinc monotherapy is not as effective as chelating agents in treatment of Wilson
      disease.
AB  - BACKGROUND & AIMS: Wilson disease is a genetic disorder that affects copper
      storage, leading to liver failure and neurologic deterioration. Patients are
      treated with copper chelators and zinc salts, but it is not clear what approach
      is optimal because there have been few studies of large cohorts. We assessed long
      term outcomes of different treatments. METHODS: Patients in tertiary care centers
      were retrospectively analyzed (n = 288; median follow-up time, 17.1 years) for
      adherence to therapy, survival, treatment failure, and adverse events from
      different treatment regimens (chelators, zinc, or a combination). Hepatic
      treatment failure was defined as an increase in activity of liver enzymes
      (aspartate aminotransferase, alanine aminotransferase, and gamma
      glutamyltransferase) >2-fold the upper limit of normal or >100% of baseline with
      an increase in urinary copper excretion. RESULTS: The median age at onset of
      Wilson disease was 17.5 years. Hepatic and neuropsychiatric symptoms occurred in
      196 (68.1%) and 99 (34.4%) patients, respectively. Hepatic treatment failure
      occurred more often from zinc therapy (14/88 treatments) than from chelator
      therapy (4/313 treatments; P < .001). Actuarial survival, without
      transplantation, showed an advantage for chelating agents (P < .001 vs zinc).
      Changes in treatment resulted mostly from adverse events, but the frequency did
      not differ between groups. Patients who did not respond to zinc therapy showed
      hepatic improvement after reintroduction of a chelating agent. CONCLUSIONS:
      Treatments with chelating agents or zinc salt are effective in most patients with
      Wilson disease; chelating agents are better at preventing hepatic deterioration.
      It is important to identify patients who do not respond to zinc therapy and have
      increased activities of liver enzymes, indicating that a chelating agent should
      be added to the therapeutic regimen.

PMID- 21185836
TI  - 5-Fluorouracil adjuvant chemotherapy does not increase survival in patients with
      CpG island methylator phenotype colorectal cancer.
AB  - BACKGROUND & AIMS: 5-Fluorouracil (5-FU)-based adjuvant chemotherapy does not
      increase survival times of patients with colorectal tumors with microsatellite
      instability. We determined the response of patients with colorectal tumors with
      the CpG island methylator phenotype (CIMP) to 5-FU-based therapy. METHODS: We
      analyzed a population-based cohort of 302 patients with colorectal cancer (CRC)
      for a median follow-up time of 50.7 months. CIMP status was determined by
      analysis of the CACNAG1, SOCS1, RUNX3, NEUROG1, and MLH1 promoters; tumors were
      considered to be CIMP positive if at least 3 promoters were methylated. RESULTS:
      Tumors from 29.5% of patients (89/302) were CIMP positive; CIMP status did not
      influence disease-free survival (DFS; log-rank = 0.3). Of tumors of TNM stages II
      III (n = 196), 32.7% were CIMP positive. Among patients with stages II-III CRC
      who did not receive adjuvant 5-FU chemotherapy, those with CIMP-positive tumors
      had longest times of DFS (log-rank = 0.04); In patients who received
      chemotherapy, those with CIMP-positive tumors had shorter times of DFS (log-rank
      = 0.02). In patients with CIMP-negative tumors, adjuvant 5-FU chemotherapy
      significantly increased time of DFS (log-rank = 0.00001). However, in patients
      with CIMP-positive tumors, adjuvant 5-FU chemotherapy did not affect time of DFS
      (log-rank = 0.7). Multivariate analysis showed a significant, independent
      interaction between 5-FU treatment and CIMP status (hazard ratio [HR], 0.6; 95%
      confidence interval [CI], 0.5-0.8). Among patients with CIMP-positive tumors,
      adjuvant chemotherapy was not an independent predictor of outcome (HR, 0.8; 95%
      CI, 0.3-2.0). In patients who did not receive adjuvant 5-FU chemotherapy, CIMP
      status was the only independent predictor of survival (HR, 2.0; 95% CI, 1.1-3.8).
      CONCLUSIONS: Patients with CIMP-positive colorectal tumors do not benefit from 5
      FU-based adjuvant chemotherapy.

PMID- 21185838
TI  - Sexy thoughts: effects of sexual cognitions on testosterone, cortisol, and
      arousal in women.
AB  - Previous research suggests that sexual stimuli increase testosterone (T) in women
      and shows inconsistent effects of sexual arousal on cortisol (C), but effects of
      cognitive aspects of arousal, rather than behaviors or sensory stimuli, are
      unclear. The present study examined whether sexual thoughts affect T or C and
      whether hormonal contraceptive (HC) use moderated this effect, given mixed
      findings of HC use confounding hormone responses. Participants (79 women)
      provided a baseline saliva sample for radioimmunoassay. We created the Imagined
      Social Situation Exercise (ISSE) to test effects of imagining social interactions
      on hormones, and participants were assigned to the experimental (sexual) or one
      of three control (positive, neutral, stressful) conditions. Participants provided
      a second saliva sample 15 min post-activity. Results indicated that for women not
      using HCs, the sexual condition increased T compared to the stressful or positive
      conditions. In contrast, HC using women in the sexual condition had decreased T
      relative to the stressful condition and similar T to the positive condition. The
      effect was specific to T, as sexual thoughts did not change C. For participants
      in the sexual condition, higher baseline T predicted larger increases in sexual
      arousal but smaller increases in T, likely due to ceiling effects on T. Our
      results suggest that sexual thoughts change T but not C, baseline T levels and HC
      use may contribute to variation in the T response to sexual thoughts, and
      cognitive aspects of sexual arousal affect physiology.

PMID- 21185837
TI  - Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation.
AB  - BACKGROUND & AIMS: The transient receptor potential (TRP) channels TRPV1 and
      TRPA1 have each been associated with regulation of efferent properties of primary
      afferent neurons that initiate neurogenic inflammation and are required for the
      development of inflammatory hyperalgesia. To evaluate the role of these channels
      in producing pain during pancreatic inflammation, we studied pancreatic nodose
      ganglion (NG) and dorsal root ganglion (DRG) sensory neurons (identified by
      content of retrograde tracer) and behavioral outcomes in a mouse model of acute
      pancreatitis. METHODS: Pancreatic inflammation was induced by 8 hourly injections
      of cerulein (50 MUg/kg). The extent of inflammation, pancreatic neuron TRP
      channel expression and function and excitability, and pain-related behaviors were
      evaluated over the course of the following week. RESULTS: Histology and
      myeloperoxidase activity confirmed pancreatic inflammation that was associated
      with increased excitability and messenger RNA expression of the TRP channels in
      NG and DRG pancreatic neurons. Calcium imaging of pancreatic NG and DRG neurons
      from mice given cerulein revealed increased responses to TRP agonists. TRPV1 and
      TRPA1 antagonists attenuated cerulein-induced pain behaviors and pancreatic
      inflammation; they had a synergistic effect. CONCLUSIONS: Pancreatic inflammation
      significantly increased the expression and functional properties of TRPV1 and
      TRPA1, as well as the excitability of pancreatic sensory neurons in vagal and
      spinal pathways. TRP channel antagonists acted synergistically to reverse
      pancreatic inflammation and associated pain behaviors; reagents that target
      interactions between these channels might be developed to reduce pain in patients
      with acute pancreatitis.

PMID- 21185839
TI  - HMR 1098 is not an SUR isotype specific inhibitor of heterologous or sarcolemmal
      K ATP channels.
AB  - Murine ventricular and atrial ATP-sensitive potassium (K(ATP)) channels contain
      different sulfonylurea receptors (ventricular K(ATP) channels are Kir6.2/SUR2A
      complexes, while atrial K(ATP) channels are Kir6.2/SUR1 complexes). HMR 1098, the
      sodium salt of HMR 1883 {1-[[5-[2-(5-chloro-o-anisamido)ethyl]-2
      methoxyphenyl]sulfonyl]-3-methylthiourea}, has been considered as a selective
      sarcolemmal (i.e. SUR2A-dependent) K(ATP) channel inhibitor. However, it is not
      clear whether HMR 1098 would preferentially inhibit ventricular K(ATP) channels
      over atrial K(ATP) channels. To test this, we used whole-cell patch clamp
      techniques on mouse atrial and ventricular myocytes as well as (86)Rb(+) efflux
      assays and excised inside-out patch clamp techniques on Kir6.2/SUR1 and
      Kir6.2/SUR2A channels heterologously expressed in COSm6 cells. In mouse atrial
      myocytes, both spontaneously activated and diazoxide-activated K(ATP) currents
      were effectively inhibited by 10 MUM HMR 1098. By contrast, in ventricular
      myocytes, pinacidil-activated K(ATP) currents were inhibited by HMR 1098 at a
      high concentration (100 MUM) but not at a low concentration (10 MUM). Consistent
      with this finding, HMR 1098 inhibits (86)Rb(+) effluxes through Kir6.2/SUR1 more
      effectively than Kir6.2/SUR2A channels in COSm6 cells. In excised inside-out
      patches, HMR 1098 inhibited Kir6.2/SUR1 channels more effectively, particularly
      in the presence of MgADP and MgATP (mimicking physiological stimulation).
      Finally, dose-dependent enhancement of insulin secretion from pancreatic islets
      and decrease of blood glucose level confirm that HMR 1098 is an inhibitor of
      Kir6.2/SUR1-composed K(ATP) channels.

PMID- 21185840
TI  - Suppression of NHE1 by small interfering RNA inhibits HIF-1alpha-induced
      angiogenesis in vitro via modulation of calpain activity.
AB  - Hypoxia-inducible factor-1 (HIF-1) orchestrates angiogenesis under hypoxic
      conditions mainly due to increased expression of such target genes as vascular
      endothelial growth factor (VEGF). Na+/H+exchanger-1 (NHE1), a potential HIF
      target gene product, plays a pivotal role in proliferation, survival, migration,
      adhesion and so on. However, it is unknown whether NHE1 is involved in HIF-1alpha
      induced angiogenesis. This present study demonstrated that the expression of NHE1
      was much higher in human umbilical vein endothelial cells (HUVECs) infected with
      adenovirus encoding HIF-1alpha (rAd-HIF) than with vacuum adenovirus (vAd). HIF
      1alpha also increased the expression of VEGF, the expression and activity of
      calpains, and the intracellular pH. Moreover, small interfering RNA targeting
      NHE1 (NHE1 siRNA) dramatically decreased the expression of NHE1 and thus lowered
      the intracellular pH, and it also attenuated the protein expression of calpain-2
      but not calpain-1, resulting in the lower calpain activity. Furthermore, HIF
      1alpha enhanced the proliferation, migration and Matrigel tube formation, which
      were inhibited by NHE1 siRNA. Finally, the inhibitory effect of NHE1 siRNA was
      reversed by VEGF and the reversibility of the later was abrogated by the calpain
      inhibitor ALLM. In conclusion, the findings have revealed that NHE1 might
      participate in HIF-1-induced angiogenesis due, at least in part, to the
      alteration of the calpain activity, suggesting that NHE1 as well as calpains
      might represent a potential target of controlling angiogenesis in response to the
      hypoxic stress under various pathological conditions.

PMID- 21185842
TI  - Hypothermia postpones DNA damage repair in irradiated cells and protects against
      cell killing.
AB  - Hibernation is an established strategy used by some homeothermic organisms to
      survive cold environments. In true hibernation, the core body temperature of an
      animal may drop to below 0 degrees C and metabolic activity almost cease. The
      phenomenon of hibernation in humans is receiving renewed interest since several
      cases of victims exhibiting core body temperatures as low as 13.7 degrees C have
      been revived with minimal lasting deficits. In addition, local cooling during
      radiotherapy has resulted in normal tissue protection. The experiments described
      in this paper were prompted by the results of a very limited pilot study, which
      showed a suppressed DNA repair response of mouse lymphocytes collected from
      animals subjected to 7-Gy total body irradiation under hypothermic (13 degrees C)
      conditions, compared to normothermic controls. Here we report that human BJ-hTERT
      cells exhibited a pronounced radioprotective effect on clonogenic survival when
      cooled to 13 degrees C during and 12h after irradiation. Mild hypothermia at 20
      and 30 degrees C also resulted in some radioprotection. The neutral comet assay
      revealed an apparent lack on double strand break (DSB) rejoining at 13 degrees C.
      Extension of the mouse lymphocyte study to ex vivo-irradiated human lymphocytes
      confirmed lower levels of induced phosphorylated H2AX (gamma-H2AX) and
      persistence of the lesions at hypothermia compared to the normal temperature.
      Parallel studies of radiation-induced oxidatively clustered DNA lesions (OCDLs)
      revealed partial repair at 13 degrees C compared to the rapid repair at 37
      degrees C. For both gamma-H2AX foci and OCDLs, the return of lymphocytes to 37
      degrees C resulted in the resumption of normal repair kinetics. These results, as
      well as observations made by others and reviewed in this study, have implications
      for understanding the radiobiology and protective mechanisms underlying
      hypothermia and potential opportunities for exploitation in terms of protecting
      normal tissues against radiation.

PMID- 21185844
TI  - Dose-responsiveness and persistence of microRNA expression alterations induced by
      cigarette smoke in mouse lung.
AB  - Our previous studies demonstrated that exposure to cigarette smoke (CS), either
      mainstream or environmental, results in a remarkable downregulation of microRNA
      expression in the lung of both mice and rats. The goals of the present study were
      to evaluate the dose responsiveness to CS and the persistence of microRNA
      alterations after smoking cessation. ICR (CD-1) neonatal mice were exposed whole
      body to mainstream CS, at the doses of 119, 292, 438, and 631mg/m(3) of total
      particulate matter. Exposure started within 12h after birth and continued daily
      for 4 weeks. The levels of bulky DNA adducts and 8-oxo-7,8-dihydro-2'
      deoxyguanosine (8-oxodGuo) were measured by (32)P postlabeling procedures, and
      the expression of 697 mouse microRNAs was analyzed by microarray. The highest CS
      dose was lethal. Exposure to CS caused a dose-dependent increase of DNA
      alterations. DNA adducts and, even more sharply, 8-oxodGuo were reverted 1 and 4
      weeks after smoking cessation. Exposure to CS resulted in an evident
      dysregulation of microRNA expression profiles, mainly in the sense of
      downregulation. The two lowest doses were not particularly effective, while the
      highest nonlethal dose produced extensive microRNA alterations. The expression of
      most downregulated microRNAs, including among others 7 members of the let-7
      family, was restored one week after smoking cessation. However, the recovery was
      incomplete for a limited array of microRNAs, including mir-34b, mir-345, mir-421,
      mir-450b, mir-466, and mir-469. Thus, it appears that microRNAs mainly behave as
      biomarkers of effect and that exposure to high-dose, lasting for an adequate
      period of time, is needed to trigger the CS-related carcinogenesis process in the
      experimental animal model used.

PMID- 21185843
TI  - Antroquinonol inhibits NSCLC proliferation by altering PI3K/mTOR proteins and
      miRNA expression profiles.
AB  - Antroquinonol a derivative of Antrodia camphorata has been reported to have
      antitumor effects against various cancer cells. However, the effect of
      antroquinonol on cell signalling and survival pathways in non-small cell lung
      cancer (NSCLC) cells has not been fully demarcated. Here we report that
      antroquinonol treatment significantly reduced the proliferation of three NSCLC
      cells. Treatment of A549 cells with antroquinonol increased cell shrinkage,
      apoptotic vacuoles, pore formation, TUNEL positive cells and increased Sub-G1
      cell population with respect to time and dose dependent manner. Antroquinonol
      treatment not only increased the Sub-G1 accumulation but also reduced the protein
      levels of cdc2 without altering the expression of cyclin B1, cdc25C, pcdc2, and
      pcdc25C. Antroquinonol induced apoptosis was associated with disrupted
      mitochondrial membrane potential and activation of Caspase 3 and PARP cleavage in
      A549 cells. Moreover, antroquinonol treatment down regulated the expression of
      Bcl2 proteins, which was correlated with the decreased PI3K and mTOR protein
      levels without altering pro apoptotic and anti apoptotic proteins. Results from
      the microarray analysis demonstrated that antroquinonol altered the expression
      level of miRNAs compared with untreated control in A549 cells. The data
      collectively suggested the antiproliferative effect of antroquinonol on NSCLC
      A549 cells, which provides useful information for understanding the anticancer
      mechanism influenced by antroquinonol and is the first report to suggest that
      antroquinonol may be a promising chemotherapeutic agent for lung cancer.

PMID- 21185841
TI  - Clustered DNA lesion repair in eukaryotes: relevance to mutagenesis and cell
      survival.
AB  - A clustered DNA lesion, also known as a multiply damaged site, is defined as >= 2
      damages in the DNA within 1-2 helical turns. Only ionizing radiation and certain
      chemicals introduce DNA damage in the genome in this non-random way. What is now
      clear is that the lethality of a damaging agent is not just related to the types
      of DNA lesions introduced, but also to how the damage is distributed in the DNA.
      Clustered DNA lesions were first hypothesized to exist in the 1990s, and work has
      progressed where these complex lesions have been characterized and measured in
      irradiated as well as in non-irradiated cells. A clustered lesion can consist of
      single as well as double strand breaks, base damage and abasic sites, and the
      damages can be situated on the same strand or opposing strands. They include
      tandem lesions, double strand break (DSB) clusters and non-DSB clusters, and base
      excision repair as well as the DSB repair pathways can be required to remove
      these complex lesions. Due to the plethora of oxidative damage induced by
      ionizing radiation, and the repair proteins involved in their removal from the
      DNA, it has been necessary to study how repair systems handle these lesions using
      synthetic DNA damage. This review focuses on the repair process and mutagenic
      consequences of clustered lesions in yeast and mammalian cells. By examining the
      studies on synthetic clustered lesions, and the effects of low vs high LET
      radiation on mammalian cells or tissues, it is possible to extrapolate the
      potential biological relevance of these clustered lesions to the killing of tumor
      cells by radiotherapy and chemotherapy, and to the risk of cancer in non-tumor
      cells, and this will be discussed.

PMID- 21185845
TI  - Chromatin dynamics during cell cycle mediate conversion of DNA damage into
      chromatid breaks and affect formation of chromosomal aberrations: biological and
      clinical significance.
AB  - The formation of diverse chromosomal aberrations following irradiation and the
      variability in radiosensitivity at different cell-cycle stages remain a long
      standing controversy, probably because most of the studies have focused on
      elucidating the enzymatic mechanisms involved using simple DNA substrates. Yet,
      recognition, processing and repair of DNA damage occur within the nucleoprotein
      complex of chromatin which is dynamic in nature, capable of rapid unfolding,
      disassembling, assembling and refolding. The present work reviews experimental
      work designed to investigate the impact of chromatin dynamics and chromosome
      conformation changes during cell-cycle in the formation of chromosomal
      aberrations. Using conventional cytogenetics and premature chromosome
      condensation to visualize interphase chromatin, the data presented support the
      hypothesis that chromatin dynamic changes during cell-cycle are important
      determinants in the conversion of sub-microscopic DNA lesions into chromatid
      breaks. Consequently, the type and yield of radiation-induced chromosomal
      aberrations at a given cell-cycle-stage depends on the combined effect of DNA
      repair processes and chromatin dynamics, which is cell-cycle-regulated and
      subject to up- or down-regulation following radiation exposure or genetic
      alterations. This new hypothesis is used to explain the variability in
      radiosensitivity observed at various cell-cycle-stages, among mutant cells and
      cells of different origin, or among different individuals, and to revisit
      unresolved issues and unanswered questions. In addition, it is used to better
      understand hypersensitivity of AT cells and to provide an improved predictive G2
      assay for evaluating radiosensitivity at individual level. Finally, experimental
      data at single cell level obtained using hybrid cells suggest that the proposed
      hypothesis applies only to the irradiated component of the hybrid.

PMID- 21185846
TI  - Repair and biochemical effects of DNA-protein crosslinks.
AB  - Genomic DNA is associated with various structural, regulatory, and transaction
      proteins. The dynamic and reversible association between proteins and DNA ensures
      the accurate expression and propagation of genetic information. However, various
      endogenous, environmental, and chemotherapeutic agents induce DNA-protein
      crosslinks (DPCs), and hence covalently trap proteins on DNA. Since DPCs are
      extremely large compared to conventional DNA lesions, they probably impair many
      aspects of DNA transactions such as replication, transcription, and repair due to
      steric hindrance. Recent genetic and biochemical studies have shed light on the
      elaborate molecular mechanism by which cells repair or tolerate DPCs. This review
      summarizes the current knowledge regarding the repair and biochemical effects of
      the most ubiquitous form of DPCs, which are associated with no flanked DNA strand
      breaks. In bacteria small DPCs are eliminated by nucleotide excision repair
      (NER), whereas oversized DPCs are processed by RecBCD-dependent homologous
      recombination (HR). NER does not participate in the repair of DPCs in mammalian
      cells, since the upper size limit of DPCs amenable to mammalian NER is smaller
      than that of bacterial NER. Thus, DPCs are processed exclusively by HR. The
      reactivation of the stalled replication fork at DPCs by HR seems to involve fork
      breakage in mammalian cells but not in bacterial cells. In addition, recent
      proteomic studies have identified the numbers of proteins in DPCs induced by
      environmental and chemotherapeutic agents. However, it remains largely elusive
      how DPCs affect replication and transcription at the molecular level. Considering
      the extremely large nature of DPCs, it is possible that they impede the
      progression of replication and transcription machineries by mechanisms different
      from those for conventional DNA lesions. This might also be true for the DNA
      damage response and signaling mechanism.

PMID- 21185847
TI  - Egocentric and allocentric memory as assessed by virtual reality in individuals
      with amnestic mild cognitive impairment.
AB  - Present evidence suggests that medial temporal cortices subserve allocentric
      representation and memory, whereas egocentric representation and memory also
      depends on parietal association cortices and the striatum. Virtual reality
      environments have a major advantage for the assessment of spatial navigation and
      memory formation, as computer-simulated first-person environments can simulate
      navigation in a large-scale space. Twenty-nine patients with amnestic MCI (aMCI)
      were compared with 29 healthy matched controls on two virtual reality tasks
      affording to learn a virtual park (allocentric memory) and a virtual maze
      (egocentric memory). Participants further received a neuropsychological
      investigation and MRI volumetry at the time of the assessment. Results indicate
      that aMCI patients had significantly reduced size of the hippocampus bilaterally
      and the right-sided precuneus and inferior parietal cortex. aMCI patients were
      severely impaired learning the virtual park and the virtual maze. Smaller volumes
      of the right-sided precuneus were related to worse performance on the virtual
      maze. Participants with striatal lacunar lesions committed more errors than
      participants without such lesions on the virtual maze but not on the virtual
      park. aMCI patients later converting to dementia (n=15) had significantly smaller
      hippocampal size when compared with non-converters (n=14). However, both groups
      did not differ on virtual reality task performance. Our study clearly
      demonstrates the feasibility of virtual reality technology to study spatial
      memory deficits of persons with aMCI. Future studies should try to design spatial
      virtual reality tasks being specific enough to predict conversion from MCI to
      dementia and conversion from normal to MCI.

PMID- 21185848
TI  - Post-weaning chronic social isolation produces profound behavioral dysregulation
      with decreases in prefrontal cortex synaptic-associated protein expression in
      female rats.
AB  - Early life stressors in rodents, including maternal separation and social
      isolation, have been shown to disrupt brain development and profoundly affect a
      wide-range of behaviors in adult animals. In this study, we focus on the
      development of female Sprague-Dawley rats in the presence and absence of
      conspecifics during the critical period of social play. Similar studies in male
      rodents have shown that this form of social deprivation results in dysregulated
      dopaminergic and serotonergic functions in the brain with core features of
      neuropsychiatric disorders including anxiety disorder and schizophrenia. Here we
      examined the behavioral and biochemical effects of post-weaning social isolation
      in female rats. Our findings demonstrated that isolation rearing produced marked
      deficits in social interaction behaviors and increased anxiety in open-field and
      novelty-suppressed feeding tests. The expression of synaptic-associated proteins
      PSD95 and synapsin I as well as glutamate receptors subunits GluR1 and NR1 in the
      prefrontal cortex (PFC) were significantly reduced in isolation-reared female
      rats. Current findings provide evidence that in female rats, post-weaning
      environmental disruption can result in profound dysregulation of synapse-related
      proteins and behavior.

PMID- 21185849
TI  - An ocular mucosal administration of nanoparticles containing DNA vaccine pRSC-gD
      IL-21 confers protection against mucosal challenge with herpes simplex virus type
      1 in mice.
AB  - Herpes stromal keratitis (HSK) is a chronic inflammatory process caused by the
      infection of herpes simplex virus type 1 (HSV-1). Development of a HSV-1 vaccine
      is a priority because these infections are common and cannot be well prevented.
      It appears that the potential of nanocarriers in DNA vaccination will be required
      to augment the immune response to DNA vaccines. Therefore, in the study,
      nanoparticles Fe(3)O(4) coated with glutamic acid, DNA vaccine pRSC-gD-IL-21 and
      polyethylenimine were prepared and immunized in the mice by ocular mucosal
      administration. The immune responses and protection efficiency against HSV-1
      challenge were also tested. The results showed that the nanoparticles containing
      DNA vaccine pRSC-gD-IL-21 induced mice to generate higher levels of specific
      neutralizing antibody, sIgA in tears, and IFN-gamma, IL-4 in serum, and to
      enhance the cytotoxicities of NK cells and splenocytes as well as splenocyte
      proliferative response to glycoprotein D compared with those of the control mice.
      More importantly, the mice immunized with the experimental vaccine showed less
      HSK degree than that of the control mice after HSV-1 challenge of the murine
      ocular mucosa. In conclusion, an ocular mucosal administration of nanoparticles
      containing DNA vaccine confers strong specific immune responses and effective
      inhibition of HSK in a HSV-1 infected murine model.

PMID- 21185850
TI  - Attitudinal and demographic predictors of measles, mumps and rubella (MMR)
      vaccine acceptance: development and validation of an evidence-based measurement
      instrument.
AB  - BACKGROUND AND OBJECTIVE: Parents' attitudes toward MMR vaccine and measles,
      mumps and rubella infections relate to their child's MMR status, therefore
      improving these attitudes is central to improving current suboptimal MMR uptake.
      However, no study has yet combined evidence-based, comprehensive and
      psychometrically validated assessment of these attitudes with reliable objective
      MMR status data, in order to identify through multivariate analyses the strongest
      attitudinal predictors of MMR uptake for interventions to target. The present
      study fills this lacuna by developing and testing a robust evidence-based MMR
      attitudes measurement instrument. DESIGN: Cross-sectional self-administered
      postal/telephone questionnaire with objective behavioural outcome. SETTING AND
      PARTICIPANTS: 535 parents of children aged 5-18 in London and north-west England,
      UK (response rate 18.1%). Recruitment via Primary Care Trust records, age
      stratified purposive sample with suboptimally immunised cases oversampled. MAIN
      OUTCOME MEASURES: Parents' responses to evidence-based measurement instrument
      comprising 20 attitude/previous behaviour items (collapsing to 5 scales) and 7
      demographic items, and their children's PCT-recorded 5th birthday status for MMR
      dose 1 (on-time, late or none) and MMR dose 2 (on-time or none). RESULTS: The
      attitudes measurement instrument was psychometrically robust: content valid, and
      demonstrating good or acceptable internal consistency (Cronbach's alpha=0.55-0.75
      for all scales), test-retest reliability (Pearson's correlation >0.60-0.80,
      p<0.01 to <0.001 for all scales and 11 individual items), concurrent/construct
      validity (t-tests for difference between MMR status groups p<0.05 for four scales
      and thirteen individual items), and predictive/criterion validity (OR=0.66, 95%
      confidence interval=0.48-0.92 to OR=1.97, 95% CI=1.18-3.31 for three scales and
      five individual items). Black and minority ethnicity (OR=1.94, 95% CI=1.15-3.30
      to OR=4.15, 95% CI=2.40-7.19), positive MMR attitudes (OR=1.63, 95% CI=1.00-2.66
      to OR=1.97, 95% CI=1.18-1.31), and positive social attitudes (OR=1.64, 95%
      CI=1.23-2.40 to OR=1.72, 95% CI=1.13-2.38) independently predicted uptake for
      both MMR doses. MMR status groups differed most strongly on preference for single
      measles, mumps and rubella vaccines (6-9% variance in status explained), previous
      MMR acceptance/rejection (5-9%), and wishing to protect others through
      vaccinating one's own child (6-8%). CONCLUSIONS: The measurement instrument is
      robust on multiple validity and reliability dimensions, and is appropriate for
      use in research and practice as a tool for designing and evaluating
      interventions. Parents appear to act in line with their attitudes toward MMR
      vaccine, though attitudes toward measles infection bore little relation to MMR
      uptake. This study indicates populations and attitudes to be prioritized in MMR
      uptake improvement interventions.

PMID- 21185851
TI  - The changing epidemiology of varicella incidence after implementation of the one
      dose varicella vaccination policy.
AB  - The varicella vaccine has been available in the Taiwan market since July 1997.
      Beginning 1998-1999, Taipei City and Taichung City/County as the early launch
      areas included the varicella vaccine in their free pediatric vaccination
      programs. By contrast, the national free vaccination program was not implemented
      until 2004. We aim to investigate the changing epidemiology of varicella
      incidence through an analysis of age-period-cohort effects. With the greatest
      decrease in varicella incidence occurring in children aged below 6, the incidence
      of varicella shifted to older age groups as reflected in different birth cohorts.
      The current study provides important implications for the current vaccination
      policy.

PMID- 21185852
TI  - AIK-C measles vaccine expressing fusion protein of respiratory syncytial virus
      induces protective antibodies in cotton rats.
AB  - Respiratory syncytial virus (RSV) is the most common cause of respiratory
      infection in infants, and no vaccine is available. In this report, recombinant
      AIK-C measles vaccines, expressing the RSV G or F protein of subgroup A
      (MVAIK/RSV/G or F), were investigated as a RSV vaccine candidate. MVAIK/RSV/G or
      F had the original ts phenotype and expressed RSV/G or F protein. Cross-reactive
      neutralizing antibodies against RSV subgroups A and B were detected in cotton
      rats immunized intramuscularly with MVAIK/RSV/F but not MVAIK/RSV/G. In cotton
      rats infected with RSV, RSV was recovered and lung histopathological finding was
      compatible with interstitial pneumonia, demonstrating thickening of alveolar
      walls and infiltration of mononuclear cells. When cotton rats immunized with
      MVAIK/RSV/F were challenged with homologous RSV subgroup A, no infectious RSV was
      recovered and very mild inflammation was noted without RSV antigen expression.
      When they were challenged with subgroup B, protective efficacy decreased. When
      cotton rats immunized with MVAIK/RSV/G were challenged with RSV subgroup A, low
      levels of infectious virus were recovered from lung. When challenged with
      subgroup B, no protective effects was demonstrated, demonstrating large amounts
      of RSV antigen in bronchial-epithelial cells. MVAIK/RSV/F is promising candidate
      and protective effects should be confirmed in monkey model.

PMID- 21185853
TI  - The mitogenic effect of testosterone and 17beta-estradiol on airway smooth muscle
      cells.
AB  - Airway disease distribution and/or severity exhibit sex differences suggesting
      that sex hormones are involved in the respiratory system physiology and
      pathophysiology. The implication of airway smooth muscle cells (ASMCs) in the
      physiology of the airways and the pathogenetic mechanism of airway remodeling is
      of great interest. Therefore, we studied the effect of testosterone and 17beta
      estradiol on ASMC proliferation and the mechanisms involved. Cell proliferation
      was estimated using the methyl-[3H]thymidine incorporation and Cell Titer 96(r)
      AQueous One Solution Assay methods. ASMC isolated from adult male or female
      rabbit trachea were incubated with testosterone (1 pM-1 MUM) or 17beta-estradiol
      (1 pM-1 MUM), in the presence or absence of the androgen receptor antagonist
      flutamide (10 nM) or estrogen receptor antagonist ICI182780 (10 nM), as well as
      of the PI3K inhibitors LY294002 (20 MUM) or wortmannin (1 MUM), or the MAPK
      inhibitors PD98059 (100 MUM) or U0126 (1 MUM). After 24 h of incubation,
      testosterone and 17beta-estradiol increased methyl-[3H]thymidine incorporation
      and cell number, in ASMC isolated from male or female animals. The induction of
      ASMC proliferation by testosterone or 17beta-estradiol was inhibited by flutamide
      or ICI182780 respectively, as well as by LY294002, wortmannin, PD98059 or U0126.
      In conclusion, testosterone and 17beta-estradiol have a mitogenic effect on ASMC,
      which is receptor-mediated and involves the MAPK and PI3K signaling pathways.
      Moreover, their effect is the same for ASMC from male and female animals. It is
      possible that gender-related differences in ASMC remodeling, may be influenced by
      the different patterns of sex steroid hormone secretion in males and females.

PMID- 21185854
TI  - Dihydroptychantol A, a macrocyclic bisbibenzyl derivative, induces autophagy and
      following apoptosis associated with p53 pathway in human osteosarcoma U2OS cells.
AB  - Dihydroptychantol A (DHA), a novel macrocyclic bisbibenzyl compound extracted
      from liverwort Asterella angusta, has antifungal and multi-drug resistance
      reversal properties. Here, the chemically synthesized DHA was employed to test
      its anti-cancer activities in human osteosarcoma U2OS cells. Our results
      demonstrated that DHA induced autophagy followed by apoptotic cell death
      accompanied with G2/M-phase cell cycle arrest in U2OS cells. DHA-induced
      autophagy was morphologically characterized by the formation of double membrane
      bound autophagic vacuoles recognizable at the ultrastructural level. DHA also
      increased the levels of LC3-II, a marker of autophagy. Surprisingly, DHA-mediated
      apoptotic cell death was potentiated by the autophagy inhibitor 3-methyladenine,
      suggesting that autophagy may play a protective role that impedes the eventual
      cell death. Furthermore, p53 was shown to be involved in DHA-mediated autophagy
      and apoptosis. In this connection, DHA increased nuclear expression of p53,
      induced p53 phosphorylation, and upregulated p53 target gene p21(Waf1/Cip1). In
      contrast, cytoplasmic p53 was reduced by DHA, which contributed to the
      stimulation of autophagy. In relation to the cell cycle, DHA decreased the
      expression of cyclin B1, a cyclin required for progression through the G2/M
      phase. Taken together, DHA induces G2/M-phase cell cycle arrest and apoptosis in
      U2OS cells. DHA-induced apoptosis was preceded by the induction of protective
      autophagy. DHA-mediated autophagy and apoptosis are associated with the
      cytoplasmic and nuclear functions of p53.

PMID- 21185855
TI  - Crowding in a detection task: external noise triggers change in processing
      strategy.
AB  - External noise paradigms have been widely used to probe different levels of
      visual processing (Pelli & Farell, 1999). A basic assumption of this paradigm is
      that the processing strategy is noise-invariant, remaining the same in low and
      high external noise. We tested this assumption by examining crowding in a
      detection task where traditionally crowding has no effect. In the first
      experiment, we measured detection thresholds for a vertically oriented sine wave
      grating (target) surrounded by four sine wave gratings (flankers) that were
      either vertically or horizontally oriented. At low noise levels, the detection
      threshold for the target was unaffected by the orientation of the flankers--there
      was no crowding. Surprisingly, however, there was crowding for detection at high
      noise levels: the threshold increased for the similarly-oriented flankers. This
      suggests that high noise triggered a change in processing strategy, increasing
      the range of space or features over which the visual signal was sampled. In a
      second experiment, we evaluated the impact of the spatial and temporal window of
      the noise on this crowding effect. Although crowding was observed for detection
      when the spatial and/or temporal window of the noise was localized (i.e.
      identical to the signal window), no crowding was observed when the noise was
      spatially and temporally extended (i.e. continuously displayed, full screen
      dynamic noise). Our results show that certain spatiotemporal distributions of
      external noise can elicit a change in processing strategy, invalidating the noise
      invariant assumption that underlies external noise paradigms. In contrast,
      spatiotemporally extended noise maintains the required noise-indifference,
      perhaps because it matches the characteristics of the internal noise that
      determines the contrast threshold in low noise.

PMID- 21185857
TI  - Characterization and antiviral function of a cytosolic sensor gene, MDA5, in
      Japanese flounder, Paralichthys olivaceus.
AB  - Cytosolic pattern recognition receptors such as retinoic acid-inducible gene I
      (RIG-I)-like receptors (RLRs) play an important role in sensing viral RNAs. The
      receptor encoded by melanoma differentiation-associated gene 5 (MDA5), an RLR,
      recognizes viral RNA in the cytoplasm and enhances antiviral response in host
      cells. The full-length MDA5 gene in Japanese flounder, Paralichthys olivaceus was
      cloned and found to have 11,251 nucleotides. MDA5 transcript abundance was
      significantly increased in whole kidney infected with viral hemorrhagic
      septicemia virus (VHSV) as well as whole kidney and peripheral blood leukocytes
      stimulated with poly I:C in vitro. Hirame natural embryo (HINAE) cells
      overexpressing MDA5 showed a lower cytopathic effect (CPE) against VHSV, hirame
      rhabdovirus (HIRRV) and infectious pancreatic necrosis virus (IPNV) infection.
      When infected with VHSV, MDA5-overexpressing HINAE cells had 24-75 fold lower
      virus titer than normal HINAE cells. These results suggest that Japanese flounder
      MDA5 is involved in the induction of antiviral response.

PMID- 21185856
TI  - Porcine S100A8 and S100A9: molecular characterizations and crucial functions in
      response to Haemophilus parasuis infection.
AB  - S100 calcium-binding protein A8 (S100A8) and S100 calcium-binding protein A9
      (S100A9) are pivotal mediators of inflammatory and protective anti-infection
      responses for the mammalian host. In this study, we present the molecular cloning
      of porcine S100A8 (pS100A8) and porcine S100A9 (pS100A9). Both genes comprise 3
      exons and 2 introns and are located on pig chromosome 4q21-q23 (closely linked to
      SW512). Homology comparison to other mammalian species affirmed that critical
      functional amino acids for post-transcriptional modification, inflammatory
      regulation, and formation of heterodimeric complexes exist in pS100A8 and
      pS100A9. Under normal conditions, both genes are preferentially expressed in
      porcine immune or immune-related organs, e.g., bone marrow, spleen, lymph nodes,
      and lung. Upon stimulation in porcine whole blood cultures with LPS or Poly(I:C),
      they are dramatically induced. Interestingly, the maximum increase of mRNA levels
      in blood cultures of Meishan pigs is significantly greater than that in Duroc
      pigs. We previously showed that pS100A8 and pS100A9 mRNA were up-regulated
      following Haemophilus parasuis (HPS) infection. We herein further confirm their
      up-regulation at the protein level in multiple HPS infected tissues (spleen, lung
      and liver). Functional cluster and network analysis based on our previous
      microarray data discovered that CEBPB may be one of the key transcription
      factors. A pS100A8/pS100A9-CASP3-SLC1A2 pathway regulating lipid metabolism was
      found. Both of their pro- and anti-inflammatory functions in response to HPS
      infection are highlighted.

PMID- 21185858
TI  - Replication-involved genes of pAL1, the linear plasmid of Arthrobacter
      nitroguajacolicus Ru61a--phylogenetic and transcriptional analysis.
AB  - The 113-kb pAL1 is the only Arthrobacter linear plasmid known; it has terminal
      inverted repeats and 5' covalently attached terminal proteins (TPs). The latter
      and a telomere-associated protein (Tap) are encoded by plasmid ORFs 102 and 101,
      respectively. As for Streptomyces linear replicons, in which both above proteins
      are instrumental in telomere patching, they are involved in pAL1 replication as
      well. However, the alignment of actinobacterial Taps and TPs revealed that pAL1
      and the linear elements from Rhodococci comprise a discrete phylogenetic group,
      clearly delineated from the streptomycetes linear plasmids. In line with such
      findings is the same genetic arrangement of ORF 101 and 102 counterparts in the
      rhodococcal elements. Furthermore, the adjacent gene (ORF100) has matches in the
      rhodococcal plasmids as well. In linear elements of Streptomyces there is no
      ORF100 homolog. Two alternative annotations are possible for ORF100 gene
      products. As RT-PCR revealed cotranscription of ORFs 100-102, the ORF100 gene
      product is presumably involved in replicative processes. Taken also into
      consideration the likely absence of an internal replication origin (other than in
      Streptomyces linear elements), we assume a distinct replication/telomere patching
      mechanism for pAL1 type replicons.

PMID- 21185859
TI  - Insertion sequence elements in Cupriavidus metallidurans CH34: distribution and
      role in adaptation.
AB  - Cupriavidus metallidurans CH34 is a beta-proteobacterium well equipped to cope
      with harsh environmental conditions such as heavy metal pollution. The strain
      carries two megaplasmids specialized in the response to heavy metals and a
      considerable number of genomic islands, transposons and insertion sequence (IS)
      elements. The latter were characterized in detail in this study, which revealed
      nine new IS elements totaling to 21 distinct IS elements from 10 different IS
      families and reaching a total of 57 intact IS copies in CH34. Analysis of all
      fully sequenced bacterial genomes revealed that relatives of these IS elements
      were mostly found in the Burkholderiaceae family (beta-proteobacteria) to which
      C. metallidurans belongs. Three IS elements were 100% conserved in other bacteria
      suggesting recent interaction and horizontal transfer between these strains. In
      addition, a number of these IS elements were associated with genomic islands,
      gene inactivation or rearrangements that alter the autotrophic growth capacities
      of CH34. The latter rearrangements gave the first molecular evidence for the
      mutator phenotype that is characteristic for various C. metallidurans strains.
      Furthermore, differential expression of some IS elements (or adjacent genes in
      the same strand orientation) was found under heavy metal stress, an environmental
      stress to which C. metallidurans CH34 is well adapted. These observations
      indicate that these IS elements play an active role in C. metallidurans CH34
      lifestyle, including its metabolic potential and adaptation under selective
      pressure.

PMID- 21185860
TI  - Top-down effects on early visual processing in humans: a predictive coding
      framework.
AB  - An increasing number of human electroencephalography (EEG) studies examining the
      earliest component of the visual evoked potential, the so-called C1, have cast
      doubts on the previously prevalent notion that this component is impermeable to
      top-down effects. This article reviews the original studies that (i) described
      the C1, (ii) linked it to primary visual cortex (V1) activity, and (iii)
      suggested that its electrophysiological characteristics are exclusively
      determined by low-level stimulus attributes, particularly the spatial position of
      the stimulus within the visual field. We then describe conflicting evidence from
      animal studies and human neuroimaging experiments and provide an overview of
      recent EEG and magnetoencephalography (MEG) work showing that initial V1 activity
      in humans may be strongly modulated by higher-level cognitive factors. Finally,
      we formulate a theoretical framework for understanding top-down effects on early
      visual processing in terms of predictive coding.

PMID- 21185862
TI  - Vascular graft infections in the intensive care unit: clinical spectrum and
      prognostic factors.
AB  - OBJECTIVES: To report clinical characteristics and prognosis of vascular graft
      infections in Intensive Care Unit (ICU). METHODS: Thirty seven patients
      consecutively admitted in ICU for suspected or definite vascular graft infection
      between January 2006 and June 2009 were included. RESULTS: Staphylococcus species
      (n = 18) and enterobacteriae (n = 16) were the most frequent causative organisms.
      Twenty six patients (70%) needed mechanical ventilation. Further surgical
      procedures were performed in 7 patients (19%). In case of definite infection,
      mortality in ICU was 33%. In non survivors, shock (92% vs 42%, p = 0.01), age >
      70 years (73% vs 27%, p = 0.04), POSSUM score > 45 (73% vs 27%, p = 0.04) and
      extra-anatomic bypass (45% vs 14%, p = 0.05) were more frequent, intra-operative
      volume of red cells transfusion (6 +/- 3 vs 3 +/- 2 units, p = 0.006) and of
      fresh frozen plasma (2.8 +/- 2.8 vs 0.7 +/- 1.2 units, p = 0.02), and SAPS II
      score (58 +/- 26 vs 38 +/- 17, p = 0.03) were higher. Proportion of adequate
      initial antibiotic therapy was similar in survivors and non survivors (91% vs
      100%, p = 0.4). Proportion of patients treated with an aminoglycoside tended to
      be higher in survivors (59% vs 27%, p = 0.07). By multivariate analysis, only
      shock was associated with death in ICU (AOR: 16.3; 95% CI: 1.7-152.1; p = 0.01).
      CONCLUSIONS: Vascular graft infection carries high morbidity and mortality rates
      in ICU. Extra-anatomic bypass might be associated with higher mortality. Early
      aminoglycoside prescription might be protective.

PMID- 21185861
TI  - Common and distinct networks underlying reward valence and processing stages: a
      meta-analysis of functional neuroimaging studies.
AB  - To better understand the reward circuitry in human brain, we conducted activation
      likelihood estimation (ALE) and parametric voxel-based meta-analyses (PVM) on 142
      neuroimaging studies that examined brain activation in reward-related tasks in
      healthy adults. We observed several core brain areas that participated in reward
      related decision making, including the nucleus accumbens (NAcc), caudate,
      putamen, thalamus, orbitofrontal cortex (OFC), bilateral anterior insula,
      anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC), as well as
      cognitive control regions in the inferior parietal lobule and prefrontal cortex
      (PFC). The NAcc was commonly activated by both positive and negative rewards
      across various stages of reward processing (e.g., anticipation, outcome, and
      evaluation). In addition, the medial OFC and PCC preferentially responded to
      positive rewards, whereas the ACC, bilateral anterior insula, and lateral PFC
      selectively responded to negative rewards. Reward anticipation activated the ACC,
      bilateral anterior insula, and brain stem, whereas reward outcome more
      significantly activated the NAcc, medial OFC, and amygdala. Neurobiological
      theories of reward-related decision making should therefore take distributed and
      interrelated representations of reward valuation and valence assessment into
      account.

PMID- 21185864
TI  - The potential role of new oral anticoagulants in the prevention and treatment of
      thromboembolism.
AB  - Thromboembolic disorders are among the major causes of morbidity and mortality,
      and anticoagulation remains the cornerstone of prevention and treatment of these
      disorders. Although effective, the well-established agents have significant
      drawbacks. Heparin, low molecular weight heparin, and fondaparinux must be given
      parenterally, which is inconvenient for long-term or home use. The orally
      administered vitamin K antagonists (such as warfarin) have a slow onset of
      action, thus requiring bridging therapy with a parenteral agent when immediate
      anticoagulation is needed (e.g. inpatients with acute deep vein thrombosis).
      Because vitamin K antagonists produce a variable anticoagulant response as a
      result of multiple drug-drug and food-drug interactions and genetic
      polymorphisms, frequent coagulation monitoring and dose adjustment are required
      to ensure a therapeutic level of anticoagulation, which is inconvenient for both
      patients and physicians. In the search for new agents to overcome the drawbacks
      associated with traditional agents, direct Factor Xa inhibitors (e.g.
      rivaroxaban, apixaban, and edoxaban) and direct thrombin inhibitors (e.g.
      dabigatran etexilate) have been developed and are undergoing late-stage clinical
      evaluation for the prevention and treatment of thromboembolic disorders. These
      new oral agents have already shown promise in large-scale clinical studies and
      data suggest that we have entered a new era with novel drugs that are closer than
      ever to the 'ideal anticoagulant'. Because these new oral agents have a rapid
      onset of action and can be given at fixed doses without the need for routine
      coagulation monitoring, they may simplify treatment paradigms and are expected to
      improve overall clinical outcome.

PMID- 21185865
TI  - Regulatory mechanism of duodenal bicarbonate secretion: Roles of endogenous
      prostaglandins and nitric oxide.
AB  - The secretion of HCO(3)(-) in the duodenum is increased by exogenous
      prostaglandin (PG) E(2) and mucosal acidification, the latter being accompanied
      by a rise in mucosal PGE(2) content and nitric oxide (NO) release. The
      stimulatory effect of PGE(2) is mediated intracellularly by both Ca(2+) and 3',5'
      adenosine cyclic adenosine monophosphate (cAMP), and this action is inhibited by
      EP3 and EP4 antagonists. The secretion is also increased by NOR3 (NO donor), and
      this response is mimicked by dibutyryl 3',5'-cyclic guanosine monophosphate
      (dbcGMP) and attenuated by indomethacin. Mucosal acidification stimulates HCO(3)(
      ) secretion with concomitant increases in mucosal PGE(2) production and NO
      release. The effects on HCO(3)(-) secretion and PGE(2) production are inhibited
      by indomethacin [nonselective cyclooxygenase (COX) inhibitor] and SC-560
      (selective COX-1 inhibitor) but not rofecoxib (selective COX-2 inhibitor). N(G)
      nitro-l-arginine methyl ester [l-NAME: nonselective NO synthase (NOS) inhibitor],
      but not aminoguanidine [selective inducible NOS inhibitor], attenuates the acid
      induced HCO(3)(-) secretion and NO release in an l-arginine-sensitive manner. In
      addition, the response to PGE(2) is potentiated by vinpocetine [phosphodiesterase
      (PDE) 1 inhibitor] and cilostamide (PDE3 inhibitor), while the response to NOR3
      is increased by vinpocetine. We conclude that endogenous PGs and NO are both
      involved in the local regulation of acid-induced duodenal HCO(3)(-) secretion;
      COX-1 and constitutive NOS are key enzymes responsible for the production of PGs
      and NO, respectively; NO stimulates HCO(3)(-) secretion by increasing PG
      production; PGE(2) stimulates HCO(3)(-) secretion via activation of EP3/EP4
      receptors; and both PDE1 and PDE3 are involved in the regulation of duodenal
      HCO(3)(-) secretion.

PMID- 21185866
TI  - Recent progress in phospholipase A2 research: from cells to animals to humans.
AB  - Mammalian genomes encode genes for more than 30 phospholipase A2s (PLA2s) or
      related enzymes, which are subdivided into several classes including low
      molecular-weight secreted PLA2s (sPLA2s), Ca2+-dependent cytosolic PLA2s
      (cPLA2s), Ca2+-independent PLA2s (iPLA2s), platelet-activating factor
      acetylhydrolases (PAF-AHs), lysosomal PLA2s, and a recently identified adipose
      specific PLA. Of these, the intracellular cPLA2 and iPLA2 families and the
      extracellular sPLA2 family are recognized as the "big three". From a general
      viewpoint, cPLA2alpha (the prototypic cPLA2 plays a major role in the initiation
      of arachidonic acid metabolism, the iPLA2 family contributes to membrane
      homeostasis and energy metabolism, and the sPLA2 family affects various
      biological events by modulating the extracellular phospholipid milieus. The cPLA2
      family evolved along with eicosanoid receptors when vertebrates first appeared,
      whereas the diverse branching of the iPLA2 and sPLA2 families during earlier
      eukaryote development suggests that they play fundamental roles in life-related
      processes. During the past decade, data concerning the unexplored roles of
      various PLA2 enzymes in pathophysiology have emerged on the basis of studies
      using knockout and transgenic mice, the use of specific inhibitors, and
      information obtained from analysis of human diseases caused by mutations in PLA2
      genes. This review focuses on current understanding of the emerging biological
      functions of PLA2s and related enzymes.

PMID- 21185863
TI  - Regulation and therapeutic targeting of peptide-activated receptor guanylyl
      cyclases.
AB  - Cyclic GMP is a ubiquitous second messenger that regulates a wide array of
      physiologic processes such as blood pressure, long bone growth, intestinal fluid
      secretion, phototransduction and lipolysis. Soluble and single-membrane-spanning
      enzymes called guanylyl cyclases (GC) synthesize cGMP. In humans, the latter
      group consists of GC-A, GC-B, GC-C, GC-E and GC-F, which are also known as NPR-A,
      NPR-B, StaR, Ret1-GC and Ret2-GC, respectively. Membrane GCs are activated by
      peptide ligands such as atrial natriuretic peptide (ANP), B-type natriuretic
      peptide (BNP), C-type natriuretic peptide (CNP), guanylin, uroguanylin, heat
      stable enterotoxin and GC-activating proteins. Nesiritide and carperitide are
      clinically approved peptide-based drugs that activate GC-A. CD-NP is an
      experimental heart failure drug that primarily activates GC-B but also activates
      GC-A at high concentrations and is resistant to degradation. Inactivating
      mutations in GC-B cause acromesomelic dysplasia type Maroteaux dwarfism and
      chromosomal mutations that increase CNP concentrations are associated with
      Marfanoid-like skeletal overgrowth. Pump-based CNP infusions increase skeletal
      growth in a mouse model of the most common type of human dwarfism, which supports
      CNP/GC-B-based therapies for short stature diseases. Linaclotide is a peptide
      activator of GC-C that stimulates intestinal motility and is in late-stage
      clinical trials for the treatment of chronic constipation. This review discusses
      the discovery of cGMP, guanylyl cyclases, the general characteristics and
      therapeutic applications of GC-A, GC-B and GC-C, and emphasizes the regulation of
      transmembrane guanylyl cyclases by phosphorylation and ATP.

PMID- 21185867
TI  - Co-culture of neurons and glia in a novel microfluidic platform.
AB  - In this study, we developed a microfluidic cell co-culture platform that permits
      individual manipulation of the microenvironment of different cell types.
      Separation of the cell culture chambers is controlled by changing the position of
      a microfabricated valve, which serves as a barrier between the chambers. This
      unique feature of our platform allowed us to maintain healthy co-cultures of
      hippocampal neurons and glia for several weeks under optimal conditions.
      Controlled fluidic exchange between the cell culture chambers provided neurons
      with a continuous supply of in situ conditioned glia media that was critical for
      their survival. Using the barrier valve, we transfected neurons in the adjacent
      chambers with green fluorescent protein (GFP) and mCherry cDNA, respectively,
      with a transfection efficiency of approximately 40%. Co-culture with glia further
      enhanced the transfection efficiency of neurons to almost 60%. Thus the
      microfluidic devices offer a novel platform for the long-term culture,
      transfection, and individual treatment of central nervous system cells.

PMID- 21185868
TI  - Human/nonhuman primate AC-PC ratio--considerations for translational brain
      measurements.
AB  - This comparative magnetic resonance imaging (MRI) analysis evaluated the ratio of
      AC-PC (anterior commissure to posterior commissure) distance measures in selected
      groups of humans and nonhuman primates (NHPs). An understanding of the basis of
      this ratio between primate species may allow more accurate translation of NHP
      stereotactic targeting measurements to upcoming human trials. MRI datasets of
      adult humans [n=21], and juvenile and adult NHPs (Macaca fascicularis [n=40], and
      Macaca mulatta [n=32]), were evaluated in a mid-sagittal plane to obtain the AC
      PC distance measure for each examined subject. Two trained evaluators, blinded to
      each other's results, carried out three separate measurements of the AC-PC length
      for each subject. Each observer carried out measurements of the entire dataset
      [n=93] before repeating the measurements two additional times. Previous dataset
      measures were not available for review at the time of subsequent measures. Inter-
      and intra-observer variabilities were not statistically significant. Minimal
      intraspecies variation was found in the AC-PC measurement of our human and NHP
      groups. We found significant interspecies differences, however, more between
      humans and NHPs, and less between the NHP groups. Regression analysis confirms
      the strong linear relationship of AC-PC distance based primarily on species in
      our study groups. Human/NHP AC-PC ratios varied between 2.1 and 2.3 based on the
      compared NHP species groups. We conclude that the scale differences in brain
      measurements between NHPs and humans described in this study allows improved
      translation of stereotactic targeting coordinates in future human clinical
      trials, which may lead to improved efficacy and safety.

PMID- 21185869
TI  - Strand-specific real-time RT-PCR for distinguishing influenza vRNA, cRNA, and
      mRNA.
AB  - Real-time RT-PCR is used to quantify individual influenza viral RNAs. However,
      conventional real-time RT-PCR, using strand-specific primers, has been shown to
      produce not only the anticipated strand-specific products, but also substantial
      amounts of non-strand-specific products, indicating lack of specificity.
      Therefore, in this study, a novel strand-specific real-time RT-PCR method was
      established to quantify the three types of influenza viral RNA (vRNA, cRNA, and
      mRNA) separately. This method is based on reverse transcription using tagged
      primers to add a 'tag' sequence at the 5' end and the hot-start method. Real-time
      PCR using the 'tag' portion as the forward primer and a segment-specific reverse
      primer ensured the specificity for quantifying the three types of RNA. Using this
      method, specific target RNA was detected at 100-100,000-folds higher level than
      other types of RNA. This method was also used to evaluate the vRNA, cRNA, and
      mRNA levels of segments 5 and 6 in MDCK cells infected with influenza A virus at
      different time point post-infections. The cRNA level was 1/10 to 1/100 lower than
      that of the vRNA and mRNA. Moreover, different dynamics of vRNA, cRNA, and mRNA
      synthesis were observed; the copy number of the vRNA gradually increased
      throughout the infection, the cRNA increased and then plateaued, while the mRNA
      increased and then decreased. This novel method thus provides data critical for
      understanding the influenza virus life cycle, including transcription,
      replication, and genome incorporation into virions.

PMID- 21185870
TI  - Improved detection and quantitation of norovirus from water.
AB  - Norovirus is associated commonly with human sewage and is responsible for
      numerous cases of waterborne and foodborne gastroenteritis every year. Assays
      using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) have
      been developed for norovirus, however, accurate detection and quantitation remain
      problematic owing to a lack of suitable positive controls. To improve enumeration
      of norovirus genomes from water, a synthetic norovirus genogroup II quantitation
      standard and competitive internal positive control were developed. The
      quantitation standard demonstrates identical amplification efficiency as wildtype
      norovirus and can be used as a viral surrogate in labs with restricted access to
      norovirus. The internal control quantifies sample inhibition, allowing for
      accurate quantitation of norovirus from complex environmental samples. Seawater
      samples spiked with sewage or bird guano were evaluated using the norovirus assay
      as part of a methods comparison study. Inhibition was detected in nine of 36
      (25%) samples, two of which proved to be positive upon re-analysis. Results
      support the specificity of this assay for human-source (sewage) fecal
      contamination. Overall, use of this quantitation standard and internal control
      signify a great advance over traditional positive controls and suggest that
      molecular techniques for viral analysis could become standardized for routine
      water quality monitoring.

PMID- 21185871
TI  - Increased plasma corticosterone levels after periaqueductal gray stimulation
      induced escape reaction or panic attacks in rats.
AB  - The hypothalamo-pituitary-adrenal (HPA) axis is involved in stress, depression
      and anxiety. Controversy exists on HPA axis activation during panic attacks
      (PAs). We examined whether the HPA axis is involved in the escape or panic-like
      response in an animal model of PAs induced by electrical stimulation of the
      dorsolateral periaqueductal gray (dlPAG) in rats. Additionally, rats were also
      treated with chronic administration of buspirone (BUSP) and escitalopram (ESCIT),
      respectively; and they were stimulated in the open-field arena for panic-like
      reaction. Levels of stress hormone corticosterone were measured following 30 min
      after escape or panic condition. Our results demonstrated that the levels of
      plasma corticosterone were significantly increased after the induction of escape
      or panic-like response in comparison with the sham animals. The levels of
      corticosterone were significantly decreased in the dlPAG stimulated groups after
      rats were treated chronically with the ESCIT but not the BUSP as compared to the
      saline treated animals. Importantly, the increase of corticosterone level after
      escape or panic-like response was paralleled by an increase of neuronal
      activation of c-Fos in both the parvocellular and magnocellular paraventricular
      nucleus of the hypothalamus. Moreover, the c-Fos data also showed a decrease in
      the number of positive cells particularly for the ESCIT as well as the BUSP in
      comparison with the saline stimulated animals. In conclusion, the present study
      clearly demonstrated that PA or escape response activates the HPA axis and it
      remains difficult to anticipate the mechanism underlying HPA axis during PAs and
      its relationship with 5-HT drugs.

PMID- 21185873
TI  - Memory impairment in rats by hippocampal administration of the serine protease
      subtilisin.
AB  - Since the serine protease subtilisin has been reported to generate a novel form
      of long-term depression (LTD) in rat hippocampal slices, the present work was
      designed to determine whether it has any effect on learning and memory processes.
      Rats were used to examine the effects of subtilisin, injected directly into the
      dorsal hippocampus, on task performance in a step-through inhibitory avoidance of
      a mild footshock. The administration of 100 ng of subtilisin into each
      hippocampus, immediately after training, was sufficient to induce a detectable
      learning deficit with a footshock stimulus of 0.5 mA. Higher doses produced dose
      related impairments in memory consolidation. These effects were not the result of
      irreversible toxicity, since rats trained with a higher amplitude footshock (0.75
      mA) were able to perform as control animals; therefore, the amnesic effect was
      not further evident. Furthermore, the administration of subtilisin before
      avoidance training did not produce any detectable effect on performance during
      the training or test sessions, indicating that neither acquisition nor
      consolidation was affected. It is concluded that the post-training administration
      of a serine protease inhibitor is able to produce robust deficits of memory
      consolidation consistent with its ability to generate LTD, raising the
      possibility that related molecules could play physiological or pathological roles
      in the modulation of learning and memory.

PMID- 21185872
TI  - NMDA preconditioning protects against quinolinic acid-induced seizures via PKA,
      PI3K and MAPK/ERK signaling pathways.
AB  - Preconditioning by N-methyl-d-aspartate (NMDA) may be promoted in vivo by the
      administration of a sub-convulsing dose of NMDA, with a neuroprotective effect
      against seizures and neuronal death induced by the infusion of quinolinic acid
      (QA) in mice. This study aimed to evaluate the participation of protein kinase C
      (PKC), cyclic AMP-dependent protein kinase (PKA), mitogen-activated protein
      kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK),
      Ca(2+)/calmodulin dependent protein kinase II (CaMKII) and phosphatidilinositol-3
      kinase (PI3K) signaling pathways in this neuroprotection model. Adult Swiss male
      mice were preconditioned with NMDA 24 h before the infusion of QA, and were
      treated with inhibitors of the aforementioned signaling pathways either 15 min
      before the preconditioning or infusion of QA. Inhibition of the PKA and PI3K
      pathways abolished the protection evoked by NMDA, and inhibition of the MEK
      pathway significantly diminished this protection. Treatment with PKC and CaMKII
      inhibitors did not alter the protection rate. Inhibition of the MEK and PKC
      pathways resulted in an increased mortality rate when followed by the infusion of
      QA, or NMDA preconditioning and QA infusion, respectively. These results suggest
      that the PKA, PI3K and MEK pathways have a crucial role in the achievement of a
      neuroprotective state following preconditioning.

PMID- 21185874
TI  - The role of a Brugia malayi p38 MAP kinase ortholog (Bm-MPK1) in parasite anti
      oxidative stress responses.
AB  - Filariasis, caused by thread-like nematode worms, affects millions of individuals
      throughout the tropics and is a major cause of acute and chronic morbidity.
      Filarial nematodes effectively evade host immunological responses and are long
      lived within their hosts. Recently an emphasis has been placed on enzymatic and
      non-enzymatic anti-oxidant systems which counteract the generation of reactive
      oxygen species (ROS) by macrophages and granulocytes, a first line of defense
      against parasites. We have characterized an anti-oxidant pathway in the filarial
      parasite Brugia malayi related to the evolutionarily conserved human mitogen
      activated p38 protein kinase and the Caenorhabditis elegans PMK-1 protein kinase
      stress pathways. We have expressed a recombinant p38/PMK-1 ortholog from B.
      malayi (Bm-MPK1) and have successfully activated the kinase with mammalian
      upstream kinases. In addition, we have demonstrated inhibition of Bm-MPK1
      activity using a panel of known p38 inhibitors. Using the potent and highly
      selective allosteric p38 inhibitor, BIRB796, we have implicated Bm-MPK1 in a
      pathway which offers B. malayi protection from the effects of ROS. Our results,
      for the first time, describe a stress-activated protein kinase pathway within the
      filarial parasite B. malayi which plays a role in protecting the parasite from
      ROS. Inhibition of this pathway may have therapeutic benefit in treating
      filariasis by increasing the sensitivity of filarial parasites to ROS and other
      reactive intermediates.

PMID- 21185875
TI  - Ghrelin, leptin and adiponectin as possible predictors of the hedonic value of
      odors.
AB  - Several lines of evidence point to a close relationship between the hormones of
      energy homeostasis and the olfactory system. Examples are the localization of
      leptin and adiponectin receptors in the olfactory system or increased activation
      of brain regions related to the palatability and the hedonic value of food in
      response to food pictures after application of ghrelin. In this preliminary
      study, we tested in 31 subjects (17 male and 14 female) if and to what extent the
      peripheral blood concentrations of "satiety" hormones, such as leptin,
      adiponectin, and ghrelin (acyl and total), are correlated with the self-ratings
      of odor pleasantness and with the objective olfactory and gustatory ability. The
      hedonic values of some odors were found to be differently rated between donors
      depending on gender and body weight. The concentrations of leptin, adiponectin
      and total ghrelin were significantly associated with the hedonic value of pepper
      black oil, but failed to show significant correlations for 5 other odors tested.
      Except for a significant association between leptin and odor identification,
      hormone concentrations were not linked to the abilities of smell and taste.
      Peripheral adipokines and gut hormones may alter the perception and pleasantness
      of specific odors, presumably either directly through their receptors in the
      olfactory system or indirectly through central interfaces between the regulation
      systems of olfaction, appetite control, memory and motivation.

PMID- 21185876
TI  - Serum salusin-alpha level in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA), a chronic inflammatory disease, leads to early and
      accelerated atherosclerosis; however, its pathogenesis is not yet fully
      documented. Salusin-alpha and beta are novel bioactive peptides. Salusin-alpha
      suppresses macrophage foam cell formation, while salusin-beta stimulates.
      Moreover, decreased serum salusin-alpha level has been reported previously in
      patients with coronary artery disease. The aims of the study were to assess serum
      salusin-alpha level and its association with predictors of atherosclerosis in a
      cohort of patients with RA. The study included 56 RA patients, 37 Behcet's
      disease (BD) patients, and 29 healthy controls (HC). TNF-alpha, IL-6 and salusin
      alpha levels, homeostasis model assessment (HOMA-IR) index and common carotid
      intima-media thickness (IMT) were determined. In the RA and BD groups, salusin
      alpha levels (p<0.001 and p<0.01, respectively) and IMTs (p<0.001 for both) were
      higher compared to the HC group. However, the level of salusin-alpha was not
      directly associated with the IMT in all the groups. Serum salusin-alpha levels
      are increased in RA and BD, although they have increased IMT. Salusin-alpha has
      been reported to have anti-atherogenic effects in previous studies. However, it
      seems that salusin-alpha does not directly affect the atherogenesis in RA and BD.
      Further studies are needed to understand the regulation of salusin-alpha and
      determination of its relations with the predictors of atherosclerosis in RA and
      BD.

PMID- 21185877
TI  - Processing of chromogranins/secretogranin in patients with diabetic retinopathy.
AB  - AIMS: Inflammation has been linked to the development of diabetic retinopathy
      (DR). Chromogranins A, B (CgA, CgB) and secretogranin II (SgII), are prohormones
      overexpressed in inflammatory diseases. The present study was conducted to
      evaluate the presence and processing of these prohormones in the vitreous of
      patients with DR (DV), compared with nondiabetic vitreous (NDV). METHODS:
      Thirteen DV and 14 NDV samples were collected during vitreoretinal surgery.
      ELISA, Western blot, RP-HPLC, dot blot, protein sequencing and mass spectrometry
      were used to study the quantitative expression and the processing of CgA, CgB and
      SgII. RESULTS: CgA, CgB and SgII presence was higher in DV than in NDV. Mean
      concentration of CgA evaluated by ELISA was 90.8 (+/- 90.1) n L-1 in DV vs. 29.7
      (+/-20.9) in NDV (p=0.039). In NDV, Western blot indicated that only short CgB
      derived peptides were identified. In DV, proteomic analyses showed that long CgA
      , CgB- and SgII-derived fragments and alpha1-antitrypsin were overexpressed,
      suggesting possible inhibition of the proteolytic process. CONCLUSIONS: This
      study shows differences in the presence and endogenous processing of CgA, CgB and
      SgII from DV vs. NDV. In DV, the increase of complete granins and the attenuation
      of their endogenous proteolytic processing could participate in DR progression by
      reducing the presence of regulatory peptides, important for the pro-/anti
      angiogenic balance in the eye.

PMID- 21185878
TI  - Bradykinin and prostaglandin E1 regulate calcitonin gene-related peptide
      expression in cultured rat sensory neurons.
AB  - Primary cultures of adult rat dorsal root ganglia (DRG) sensory neurons were used
      to determine whether bradykinin and prostaglandins E1 (PGE1), E2 (PGE2) or I2
      (PGI2) stimulate long-term calcitonin gene-related peptide (CGRP) mRNA
      accumulation and peptide release. Treatment (24 h) of neurons with either
      bradykinin or PGE1, significantly increased CGRP mRNA content and iCGRP release.
      However, PGE2 or PGI2 was without effect. Exposure of the cultured neurons to
      increasing concentrations of bradykinin or PGE1 demonstrated that the stimulation
      of CGRP expression was concentration-dependent, while time-course studies showed
      that maximal levels of CGRP mRNA accumulation and peptide release were maintained
      for at least 48 h. Treatment of the neuronal cultures with a bradykinin B2
      receptor antagonist significantly inhibited the bradykinin-induced increase in
      CGRP expression and release. In addition, preincubation of neuronal cultures with
      the cyclooxygenase inhibitor indomethacin did not alter the PGE1-mediated
      stimulation of CGRP but blocked completely the bradykinin-induced increase in
      CGRP production. Therefore, these data indicate that bradykinin and PGE1 can
      regulate the synthesis and release of CGRP in DRG neurons and that the
      stimulatory effects of bradykinin on CGRP are mediated by a cyclooxygenase
      product(s). Thus, these findings suggest a direct relationship between chronic
      alterations in bradykinin/prostaglandin production that may arise from
      pathophysiological causes and long-term changes in CGRP expression.

PMID- 21185880
TI  - SOE-LRed: A simple and time-efficient method to localize genes with point
      mutations onto the Escherichia coli chromosome.
AB  - We use a powerful method to replace wild-type genes on the chromosome of
      Escherichia coli. Using a unique form of PCR, we generate easily constructible
      gene fusions bearing single point mutations. Used in conjunction with homologous
      recombination, this method eliminates cloning procedures previously used for this
      purpose.

PMID- 21185879
TI  - Calmodulin binds HER2 and modulates HER2 signaling.
AB  - Human epidermal growth factor receptor 2 (HER2), a member of the ErbB family of
      receptor tyrosine kinases, has defined roles in neoplastic transformation and
      tumor progression. Overexpression of HER2 is an adverse prognostic factor in
      several human neoplasms and, particularly in breast cancer, correlates strongly
      with a decrease in overall patient survival. HER2 stimulates breast tumorigenesis
      by forming protein-protein interactions with a diverse array of intracellular
      signaling molecules, and evidence suggests that manipulation of these
      associations holds therapeutic potential. To modulate specific HER2 interactions,
      the region(s) of HER2 to which each target binds must be accurately identified.
      Calmodulin (CaM), a ubiquitously expressed Ca(2+) binding protein, interacts with
      multiple intracellular targets. Interestingly, CaM binds the juxtamembrane region
      of the epidermal growth factor receptor, a HER2 homolog. Here, we show that CaM
      interacts, in a Ca(2+)-regulated manner, with two distinct sites on the N
      terminal portion of the HER2 intracellular domain. Deletion of residues 676-689
      and 714-732 from HER2 prevented CaM-HER2 binding. Inhibition of CaM function or
      deletion of the CaM binding sites from HER2 significantly decreased both HER2
      phosphorylation and HER2-stimulated cell growth. Collectively, these data suggest
      that inhibition of CaM-HER2 interaction may represent a rational therapeutic
      strategy for the treatment of patients with breast cancer. This article is part
      of a Special Issue entitled: 11th European Symposium on Calcium.

PMID- 21185881
TI  - Use of signature-tagged mutagenesis to identify virulence determinants in
      Haemophilus ducreyi responsible for ulcer formation.
AB  - Elucidating the molecular mechanisms responsible for chancroid, a genital ulcer
      disease caused by Haemophilus ducreyi, has been hampered in part by the relative
      genetic intractability of the organism. A whole genome screen using signature
      tagged mutagenesis in the temperature-dependent rabbit model (TDRM) of H. ducreyi
      infection uncovered 26 mutants with a presumptive attenuated phenotype.
      Insertions in two previously recognized virulence determinants, hgbA and lspA1,
      validated this genome scanning technique. Database interrogation allowed
      assignment of 24 mutants to several functional classes, including transport,
      metabolism, DNA repair, stress response and gene regulation. The attenuated
      virulence for a 3 strain with a mutation in hicB was confirmed by individual
      infection in the TDRM. The results from this preliminary study indicate that this
      high throughput strategy will further the understanding of the pathogenesis of H.
      ducreyi infection.

PMID- 21185882
TI  - Detection of phytoplasma by loop-mediated isothermal amplification of DNA (LAMP).
AB  - Napier stunt phytoplasma (16SrXI and 16SrIII) in eastern Africa is a serious
      threat to the expansion of Napier grass (Pennisetum purpureum) farming in the
      region, where it is widely cultivated as fodder in zero grazing livestock
      systems. The grass has high potential for bio-fuel production, and has been
      adopted by farmers as a countermeasure to cereal stem borer Lepidoptera, since it
      attracts and traps the insect. Diagnosis of stunt phytoplasma have been largely
      by nested polymerase chain reaction (nPCR) targeting the 16S rRNA gene. However,
      the method is laborious, costly and technically demanding. This investigation has
      developed a simpler but effective phytoplasma diagnostic tool, called; loop
      mediated isothermal amplification of DNA (LAMP). The assay was tested on 8
      symptomatic and 8 asymptomatic plants, while its detection limit was compared to
      nested PCR using samples serially diluted from 3 ng/MUl to 0.38 pg/MUl. Molecular
      typing of LAMP products was determined by BsrI restriction digestion and Southern
      blot analysis. The assay sensitivity, positive and negative predictive values
      were estimated, while the specificity was tested on 11 phytoplasma groups. LAMP
      was specific to 5 phytoplasma groups: 16SrVI, X, XI and XVI. BsrI restriction
      digestion produced two predicted fragments, and there was specific binding of
      probe DNA to the LAMP amplicons in Southern blot analysis. The assay sensitivity
      was 100%, while the positive and negative predictive values were 63 and 100%
      respectively. LAMP was 20-fold more sensitive than nested PCR. This study
      validates LAMP for routine diagnosis of Napier stunt and other closely related
      phytoplasmas.

PMID- 21185883
TI  - The diurnal cortisol cycle and cognitive performance in the healthy old.
AB  - Associations between cognitive performance and cortisol have variously been
      reported for measures of both cortisol level and change, and for some domains of
      cognitive functioning more than others. In this study, associations between
      cortisol secretion measures and cognitive performance were examined in 50 healthy
      older people (mean age 74 years; 34 F /16 M). Participants provided 16 accurately
      timed saliva samples over 2 consecutive days to determine diurnal profiles of
      cortisol secretion. Overall cognitive performance (OCP) was measured as the
      principal component of a comprehensive battery of cognitive tests. Across a 30
      year age range, there was a strong inverse correlation between age and OCP. Age
      and poorer OCP were also associated with an attenuated cortisol awakening
      response (CAR), defined as the rise from 0-30 min after awakening, and a
      subsequent less steep fall in cortisol level over the rest of the day.
      Partialling analyses, suggested that the correlation between fall in cortisol
      over the day and OCP was independent of age. Both older age and less cortisol
      change were particularly related to poorer performance on tests of declarative
      memory and executive functioning. Our conclusions are that during the short post
      awakening period, an exception exists to the generally pertaining association
      between higher levels of cortisol and poorer cognitive performance.
      Consequentially dynamic measures reflecting the rise (CAR) and fall from the post
      awakening peak may be particularly salient in helping to explain links between
      cortisol and cognitive performance. Finally our pattern of results across
      different cognitive tests suggests an association between cortisol and those
      domains of cognitive functioning which depend crucially on the integrity of the
      hippocampus and pre-frontal cortex.

PMID- 21185884
TI  - The effects of arousal and valence on facial electromyographic asymmetry during
      blocked picture viewing.
AB  - The effect of stimulus valence and arousal on facial electromyographic (EMG)
      asymmetry was investigated to inform the debate about two contrasting hypotheses
      of emotion: the right hemisphere dominance hypothesis and the valence hypothesis.
      EMG was recorded from the left and right corrugator and zygomaticus muscles while
      participants (N = 21) viewed blocks of negative and positive pictures that were
      high or low in arousal. Ratings of valence and arousal were taken before and
      after each of the four emotion blocks. Corrugator muscle activity yielded
      evidence for left hemi-face dominance during high and low arousal negative
      picture blocks whereas zygomaticus muscle activity yielded evidence for right
      hemi-face dominance during high arousal positive picture blocks, especially early
      during the picture sequence. This pattern of results is consistent with the
      valence hypothesis.

PMID- 21185885
TI  - Cellular mechanisms by which lipoic acid confers protection during the early
      stages of cerebral ischemia: a possible role for calcium.
AB  - Lipoic acid (LA) is a naturally occurring compound and dietary supplement with
      powerful antioxidant properties. Although LA is neuroprotective in models of
      stroke, little is known about the cellular mechanisms by which it confers
      protection during the early stages of ischemia. Here, using a rat model of
      permanent middle cerebral artery occlusion (MCAO), we demonstrated that
      administration of LA 30 min prior to stroke, reduces infarct volume in a dose
      dependent manner. Whole-cell patch clamp techniques in rat brain slices were used
      to determine if LA causes any electrophysiological alterations in either healthy
      neurons or neurons exposed to oxygen and glucose deprivation (OGD). In healthy
      neurons, LA (0.005 mg/ml and 0.05 mg/ml) did not significantly change resting
      membrane potential, threshold or frequency of action potentials or synaptic
      transmission, as determined by amplitude of excitatory post synaptic currents
      (EPSCs). Similarly, in neurons exposed to OGD, LA did not alter the time course
      to loss of EPSCs. However, there was a significant delay the onset of anoxic
      depolarization as well as in the time course of the depolarization. Next,
      intracellular calcium (Ca(2+)) levels were monitored in isolated neurons using
      fura-2. Pretreatment with 0.005 mg/ml and 0.05 mg/ml LA for 30 min and 6 h did
      not significantly alter resting Ca(2+) levels or Ca(2+) response to glutamate
      (250 MUM). However, pretreatment with 0.5 mg/ml LA for 6 h significantly
      increased resting Ca(2+) levels and significantly decreased the Ca(2+) response
      to glutamate. In summary, these findings suggest that LA does not affect neuronal
      physiology under normal conditions, but can protect cells from an ischemic event.

PMID- 21185886
TI  - Loss of striatal dopaminergic terminals during the early stage in response to
      MPTP injection in C57BL/6 mice.
AB  - The molecular mechanisms underlying MPTP (1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine)-induced dopaminergic (DAergic) neuronal death in vivo are
      still not fully understood. To investigate the selective DAergic neurotoxicity,
      we have developed an immunological technique to isolate DAergic synaptosomes from
      mouse striatal tissues using an antibody against 20 amino acid residues in the
      extracellular second loop of dopamine transporter (DAT). The DAT protein level in
      the isolated DAergic synaptosomes was markedly decreased at 16 h after a single
      injection of 30 mg/kg MPTP, but not in striatal homogenate and crude synaptosomes
      fraction. GBR-12909, a dopamine uptake inhibitor, completely reversed the MPTP
      induced decrease of DAT protein in the DAergic synaptosomes. These results
      suggest that the isolated DAergic synaptosomes can be useful to identify
      mechanisms of loss of the nerve terminals.

PMID- 21185887
TI  - Encouraging regeneration in the central nervous system: is there a role for
      olfactory ensheathing cells?
AB  - The olfactory system holds a privileged position within the adult mammalian
      central nervous system; olfactory neurons undergo continual replacement and
      regeneration of synaptic contacts following injury, a feature shared by only a
      select few neuronal systems. The olfactory ensheathing cell, a glial cell found
      only in this system, is thought to play a central role in this regenerative
      process and has hence been the focus of numerous studies into promoting CNS
      regeneration following injury, in particular of the spinal cord. In trials,
      olfactory ensheathing cells have achieved some of the most promising results yet
      in promoting CNS regeneration, including a degree of functional recovery in
      humans following CNS injury. Comparatively, numerous other strategies, both those
      involving cellular transplantation and those examining neutralisation of
      inhibitory factors of the CNS, have achieved limited success. A combinational
      strategy, with olfactory ensheathing cells at its centre, is arguably the best
      way forward in encouraging effective recovery following CNS injury. This review
      examines the inhibitory environment of the CNS and the research to date on
      overcoming its effects on the regrowth of injured axons. The efficacy of
      therapies involving olfactory ensheathing cells, and the place of these therapies
      among the many other strategies being developed is examined.

PMID- 21185888
TI  - A heterozygous deletion in the glutamate decarboxylase 67 gene enhances maternal
      and fetal stress vulnerability.
AB  - Both down-regulation of glutamate decarboxylase 67 (GAD67) and maternal exposure
      to severe stress during pregnancy can increase the risk of schizophrenia and
      related psychotic disorders in the offspring. To investigate a gene-environment
      interaction, we performed the restraint-and-light stress to pregnant GAD67-GFP
      knock-in (GAD67(+/GFP)) and wild-type (GAD67(+/+)) mice three times a day for 45
      min per session during gestational day (G) 15.0-17.5. The stress hormone
      (corticosterone) level of pregnant GAD67(+/GFP) mice (the overall GABA content is
      reduced because of the destruction of one allele of the endogenous GAD67 gene)
      was higher than that of GAD67(+/+), even without stress. The fetal body weights
      (GAD67(+/+)) in the GAD67(+/GFP) mothers were lower than those in the GAD67(+/+)
      mothers. GAD67(+/GFP) fetuses exhibited higher corticosterone (CORT) levels than
      GAD67(+/+) fetuses, even in non-stressed GAD67(+/+) mothers. Fetal body weight
      decreases and CORT-increases by maternal stress (GAD67(+/+) mother) were
      significantly more in the GAD67(+/GFP) fetuses than the GAD67(+/+) fetuses. These
      results indicate that a GAD67 heterozygous deletion itself enhances vulnerability
      by many aspects, e.g., maternal stress, maternity, and being in utero. Thus, an
      abnormality in GAD67 could interact with environmental risk factors of
      psychiatric disorders, including schizophrenia.

PMID- 21185889
TI  - Mitochondrial DNA deletion mutations in patients with neuropsychiatric symptoms.
AB  - It has been suggested that mitochondrial dysfunction is important in the
      pathogenesis of psychiatric disorders such as depression, schizophrenia and
      dementia. We report herein three adult patients exhibiting such psychiatric
      symptoms as the core manifestation, accompanied by various degrees of myopathic
      symptoms. Pathological findings in biopsied skeletal muscle were compatible with
      mitochondrial myopathy in all cases. Maternal inheritance was not apparent in all
      three cases; however, two patients were born to consanguineous parents. Mutation
      analysis on the mitochondrial DNA (mtDNA) and seven nuclear genes, in which
      pathogenic mutations are known to cause mtDNA deletions, was performed. MtDNA
      deletion mutations were identified in skeletal muscles of all patients. Neither
      pathogenic mutations nor copy number variation was identified among the nuclear
      genes. Although further studies are needed, the molecular pathways inducing
      mitochondrial abnormalities may be implicated in a variety of psychiatric
      conditions.

PMID- 21185890
TI  - Identification of mixed equine rhinitis B virus infections leading to further
      insight on the relationship between genotype, serotype and acid stability
      phenotype.
AB  - Equine rhinitis B virus (ERBV) is the single species in the genus Erbovirus,
      family Picornaviridae. Equine rhinitis B viruses exist in three serotypes and are
      associated with respiratory disease in horses. Members of the species vary in
      stability at acid pH. To date there has been discordance in genotype, serotype
      and acid stability phenotype groupings. To identify capsid regions associated
      with acid stability, two viruses were serially treated at pH 3.3 to isolate acid
      stable mutants. An acid-stable mutant of the prototype acid-labile serotype 1
      virus contained a single amino acid change in the C-terminus of VP1. Similar
      treatment with a separate isolate identified a multiple ERBV serotype infection
      with acid-labile serotype 1 and acid-stable serotype 3. Dual infections were
      subsequently identified in original swabs taken from the infected horse and from
      two further cell culture passaged viruses originally isolated in Switzerland.
      Serotype specific rat antisera were produced and used to examine a collection of
      isolates from a range of genotypes, acid stability phenotypes and serotypes. In
      contrast to previous reports, we showed viruses previously classified as acid
      stable serotype 1 are in fact serotype 3 and that there is a clear association of
      serotype with genotype and acid stability phenotype in ERBVs. Additionally, we
      have shown that ERBV capsids dissociate into pentamers in acidic conditions below
      their threshold of stability, similarly to closely related viruses in the same
      family.

PMID- 21185891
TI  - Molecular detection and sequence analysis of feline Torque teno virus (TTV) in
      China.
AB  - In the present study, two isolates (SH-F1 and SH-F2) of Torque teno felis virus
      (feline TTV) were detected in 16 (12.5%) serum samples collected from cats in
      China. Their full length genomes were cloned and sequenced. The results showed
      that they were 2063bp in length and contained three open reading frames (ORFs)
      (ORF1: nt438-1748, ORF2: nt268-585 and ORF3: nt268-581, 1461-1842). Phylogenetic
      analysis showed that they were clustered with the strain of Japan (Fc-TTV4,
      AB076003) and the strain of France (PRA4, EF538878). Sequence analysis indicated
      that SH-F1 had high (97.5% and 93.3%) identity with the strain of Japan and the
      strain of France, and SH-F2 shared 94.5% and 92.1% homology with them,
      respectively. In conclusion, we demonstrated that feline TTV is present in China.

PMID- 21185892
TI  - Polysaccharide nanogel gene delivery system with endosome-escaping function: Co
      delivery of plasmid DNA and phospholipase A2.
AB  - We developed a novel gene delivery system capable of endosome disruption using a
      polysaccharide-based cationic nanogel composed of a hexadecyl group-bearing
      cationic cycloamylose nanogel (C16-catCA nanogel) and phospholipaseA(2) (PLA(2))
      to hydrolyze membrane phospholipids. C16-catCA nanogel formed nanoparticles with
      PLA(2) and pDNA by hydrophobic and electrostatic interactions. Both pDNA and
      PLA(2) were effectively internalized into cells by the C16-catCA nanogel. In
      addition, the pDNA expression level was enhanced when complexed with specific
      concentrations of PLA(2). PLA(2) complexed with C16-catCA nanogel also showed a
      similar hemolytic activity against red blood cells to that observed using native
      PLA(2). These results suggest that the C16-catCA nanogel/PLA(2) complex possesses
      membrane disruption ability when delivered into cells and triggers the subsequent
      release of pDNA from the endosome to the cytoplasm. This is the first report of
      co-delivery of pDNA and PLA(2) using the same carrier to achieve effective gene
      delivery.

PMID- 21185893
TI  - Self-assembled siRNA-PLGA conjugate micelles for gene silencing.
AB  - Biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) was conjugated to the 3'
      end of small interfering RNA (siRNA) via a disulfide bond to synthesize siRNA
      PLGA hybrid conjugates. siRNA-PLGA conjugates were spontaneously self-assembled
      to form a spherical core/shell type micellar structure of ~20 nm in an aqueous
      environment, probably by hydrophobic interaction of PLGA blocks in the core
      surrounded by an siRNA shell layer. When linear polyethylenimine was added to the
      siRNA-PLGA micelles in aqueous solution, stable siRNA-PLGA/LPEI micelles with a
      size of ~30 nm were produced via ionic complexation between siRNA and LPEI in the
      outer shell. The cationic siRNA-PLGA/LPEI micelles showed superior intracellular
      uptake and enhanced gene silencing effect, compared to naked siRNA/LPEI
      complexes. The hybrid micelle structure based on siRNA and PLGA can be
      potentially used as an efficient siRNA delivery system for gene silencing.

PMID- 21185894
TI  - Effects of distraction and focused attention on actual and perceived food intake
      in females with non-clinical eating psychopathology.
AB  - The aim of this study was to determine the effects of distraction and focused
      attention on both food intake and accuracy of perceived intake in women with non
      clinical levels of disordered eating. In a laboratory study, twenty-seven young
      women consumed three identical pasta meals once a week for three consecutive
      weeks. Meals were eaten ad libitum during a control and two test conditions, in
      which attention was either diverted away from (distraction condition) or directed
      towards food-related stimuli (focused attention condition). They also completed
      the drive for thinness, bulimia and body dissatisfaction subscales of the Eating
      Disorders Inventory-2. Intake was significantly higher in the distraction than in
      the control or focused attention conditions, but was not related to eating
      psychopathology. A measure of accuracy of perceived intake indicated that drive
      for thinness was associated with overestimation of food intake in the focused
      attention condition. This study suggests that distraction could promote food
      intake in all non-clinical consumers, irrespective of individual differences in
      eating behaviours. Furthermore, it suggests that those with a high drive for
      thinness may overestimate intake when required to focus on their food. These
      findings could have implications for mealtime interventions in the treatment of
      eating disorders.

PMID- 21185895
TI  - Just thinking about exercise makes me serve more food. Physical activity and
      calorie compensation.
AB  - Based on the findings demonstrating compensation between mental effort and
      subsequent food consumption, this article focuses on the compensatory mechanism
      between thinking about physical activity and food intake. Results from a field
      experiment indicate that simply reading about physical activity leads
      participants to compensate by serving themselves more snacks. The amount of
      snacks served was mediated by biased calorie estimation. Additionally, we also
      manipulated the way physical activity was perceived (as tiring exercise or as a
      fun activity). Although results suggest extra consumption when exercise is
      perceived as tiring, differences were not statistically significant.

PMID- 21185896
TI  - Training inhibitory control. A recipe for resisting sweet temptations.
AB  - When inhibitory control is lacking, people are more prone to indulge in high
      calorie food. This research examined whether training to inhibit food-related
      responses renders one less susceptible to temptations of high calorie food. Trait
      chocolate lovers were divided into three conditions: participants either
      consistently inhibited responding to chocolate stimuli (chocolate/no-go
      condition), consistently responded to chocolate stimuli (chocolate/go condition),
      or responded to chocolate stimuli only during half the trials (control
      condition). Chocolate consumption was measured following the manipulation with a
      taste test. Chocolate consumption did not differ between the control condition
      and the chocolate/go condition, and increased as a function of dietary restraint
      in both conditions. In the chocolate/no-go condition, however, chocolate
      consumption was significantly reduced, and higher levels of dietary restraint
      were associated with decreased chocolate intake. These findings demonstrate that
      repeatedly practicing inhibitory control over food-related responses can help
      people regain control over the consumption of high calorie food.

PMID- 21185897
TI  - Silibinin: a novel inhibitor of Abeta aggregation.
AB  - Alzheimer's disease (AD) is characterized by the abnormal aggregation of amyloid
      beta peptide (Abeta) into extracellular fibrillar deposits known as amyloid
      plaque. Inhibition of Abeta aggregation is therefore viewed as a potential method
      to halt or slow the progression of AD. It is reported that silibinin (silybin), a
      flavonoid derived from the herb milk thistle (Silybum marianum), attenuates
      cognitive deficits induced by Abeta25-35 peptide and methamphetamine. However, it
      remains unclear whether silibinin interacts with Abeta peptide directly and
      decreases Abeta peptide-induced neurotoxicity. In the present study, we
      identified, through employing a ThT assay and electron microscopic imaging that
      silibinin also appears to act as a novel inhibitor of Abeta aggregation and this
      effect showed dose-dependency. We also show that silibinin prevented SH-SY5Y
      cells from injuries caused by Abeta(1-42)-induced oxidative stress by decreasing
      H(2)O(2) production in Abeta(1-42)-stressed neurons. Taken together, these
      results indicate that silibinin may be a novel therapeutic agent for the
      treatment of AD.

PMID- 21185898
TI  - Ginsenoside Rd attenuates early oxidative damage and sequential inflammatory
      response after transient focal ischemia in rats.
AB  - We previously found that ginsenoside Rd (Rd), one of the main active ingredients
      in Panax ginseng, attenuates neuronal oxidative damage in vitro induced by
      hydrogen peroxide and oxygen-glucose deprivation. In this study, we sought to
      investigate the potential protective effects and associated mechanisms of Rd in a
      rat model of focal cerebral ischemia. Rats administered with Rd (0.1-200mg/kg) or
      vehicle was subjected to transient middle cerebral artery occlusion. Rd at the
      dose of 10-50mg/kg significantly reduced the infarct volume and improved the long
      term neurological outcome up to 6 weeks after ischemia. To evaluate the
      underlying mechanisms, in vivo free radical generation was monitored using
      microdialysis, oxidative DNA damage was identified by 8-hydroxy-deoxyguanosine
      immunostaining, oxidative protein damage was identified by the assessment of
      protein carbonyl and advanced glycosylation end products, and lipid peroxidation
      was estimated by determining the malondialdehyde and 4-hydroxynonenal formations.
      Microdialysis results displayed a prominent inhibitory effect of Rd on the
      hydroxy radical formation trapped as 2,3- and 2,5-DHBA. Early accumulations of
      DNA, protein and lipid peroxidation products were also suppressed by Rd
      treatment. Although Rd partly preserved endogenous antioxidant activities in the
      ischemic penumbra, in sham rats without stroke, endogenous antioxidant activities
      were not affected by Rd. Furthermore, we assayed sequential inflammatory response
      in a later phase after ischemia. Rd significantly eliminated inflammatory injury
      as indicated by the suppression of microglial activation, inducible nitric oxide
      synthase and cyclooxygenase-2 expression. Collectively, these findings
      demonstrated that Rd exerts neuroprotection in transient focal ischemia, which
      may involve early free radicals scavenging pathway and a late anti-inflammatory
      effect.

PMID- 21185899
TI  - Neuroprotective effect of pyruvate and oxaloacetate during pilocarpine induced
      status epilepticus in rats.
AB  - Recent research data have shown that systemic administration of pyruvate and
      oxaloacetate causes an increased brain-to-blood glutamate efflux. Since increased
      release of glutamate during epileptic seizures can lead to excitotoxicity and
      neuronal cell death, we tested the hypothesis that glutamate scavenging mediated
      by pyruvate and oxaloacetate systemic administration could have a neuroprotective
      effect in rats subjected to status epilepticus (SE). SE was induced by a single
      dose of pilocarpine (350mg/kgi.p.). Thirty minutes after SE onset, a single dose
      of pyruvate (250mg/kgi.p.), oxaloacetate (1.4mg/kgi.p.), or both substances was
      administrated. Acute neuronal loss in hippocampal regions CA1 and hilus was
      quantitatively determined five hours after SE onset, using the optical
      fractionator method for stereological cell counting. Apoptotic cascade in the
      hippocampus was also investigated seven days after SE using caspase-1 and -3
      activity assays. SE-induced neuronal loss in CA1 was completely prevented in rats
      treated with pyruvate plus oxaloacetate. The SE-induced caspase-1 activation was
      significantly reduced when rats were treated with oxaloacetate or pyruvate plus
      oxaloacetate. The treatment with pyruvate and oxaloacetate caused a
      neuroprotective effect in rats subjected to pilocarpine-induced SE.

PMID- 21185900
TI  - Functional significance of the negative-feedback regulation of ATP release via
      pannexin-1 hemichannels under ischemic stress in astrocytes.
AB  - The opening of pannexin-1 (Px1) hemichannels is regulated by the activity of
      P2X(7) receptors (P2X(7)Rs). At present, however, little is known about how
      extracellular ATP-sensitive P2X(7)Rs regulates the opening and closure of Px1
      hemichannels. Several lines of evidence suggest that P2X(7)Rs are activated under
      pathological conditions such as ischemia, resulting in the opening of Px1
      hemichannels responsible for the massive influx of Ca(2+) from the extracellular
      space and the release of ATP from the cytoplasm, leading to cell death. Here we
      show in cultured astrocytes that the suppression of the activity of P2X(7)Rs
      during simulated ischemia (oxygen/glucose deprivation, OGD) resulted in the
      opening of Px1 hemichannels, leading to the enhanced release of ATP. In addition,
      the suppression of the activity of P2X(7)Rs during OGD resulted in a significant
      increase in astrocytic damage. Both the P2X(7)Rs suppression-induced enhancement
      of the release of ATP and cell damage were reversed by co-treatment with blockers
      of Px1 hemichannels, suggesting that suppression of the activity of PX(7)Rs
      resulted in the opening of Px1 hemichannels. All these findings suggested the
      existence of a negative-feedback loop regulating the release of ATP via Px1
      hemichannels; ATP-induced suppression of ATP release. The present study indicates
      that ATP, released through Px1 hemichannels, activates P2X(7)Rs, resulting in the
      closure of Px1 hemichannels during ischemia. This negative-feedback mechanism,
      suppressing the loss of cellular ATP and Ca(2+) influx, might contribute to the
      survival of astrocytes under ischemic stress.

PMID- 21185902
TI  - Effects of alcohol withdrawal on cardiovascular system.
AB  - Alcohol withdrawal syndrome (AWS) develops after cessation of alcohol intake in
      alcoholic patients characterizing psychiatric symptoms and changes in autonomous
      nervous systems. We studied cardiovascular changes during different phases of AWS
      (1, 2, 3 and 10 days after admission for detoxification; n=34) and compared them
      with those in early recovery (at least 1 month of abstinence; n=30). The results
      study showed that cardiovascular system underwent significant changes during AWS
      characterizing the decrease of heart rate, systolic and diastolic blood
      pressures, and total peripheral resistance. Stroke index was lower during AWS
      than in early recovery. As the decreased stroke index was compensated by
      increased heart rate, cardiac index did not differ during AWS from that in early
      recovery. Increased functioning of noradrenaline (along with other central and
      peripheral regulating mechanisms) may be an important factor associated with
      cardiovascular changes in AWS. Normalization of this function after AWS leads to
      returning of cardiovascular parameters to baseline levels.

PMID- 21185901
TI  - mRNA for the EAAC1 subtype of glutamate transporter is present in neuronal
      dendrites in vitro and dramatically increases in vivo after a seizure.
AB  - The neuronal Na(+)-dependent glutamate transporter, excitatory amino acid carrier
      1 (EAAC1, also called EAAT3), has been implicated in the control of synaptic
      spillover of glutamate, synaptic plasticity, and the import of cysteine for
      neuronal synthesis of glutathione. EAAC1 protein is observed in both perisynaptic
      regions of the synapse and in neuronal cell bodies. Although amino acid residues
      in the carboxyl terminal tail have been implicated in the dendritic targeting of
      EAAC1 protein, it is not known if mRNA for EAAC1 may also be targeted to
      dendrites. Sorting of mRNA to specific cellular domains provides a mechanism by
      which signals can rapidly increase translation in a local environment; this form
      of regulated translation has been linked to diverse biological phenomena ranging
      from establishment of polarity during embryogenesis to synapse development and
      synaptic plasticity. In the present study, EAAC1 mRNA sequences were amplified
      from dendritic samples that were mechanically harvested from low-density
      hippocampal neuronal cultures. In parallel analyses, mRNA for histone deacetylase
      2 (HDAC-2) and glial fibrillary acidic protein (GFAP) was not detected,
      suggesting that these samples are not contaminated with cell body or glial mRNAs.
      EAAC1 mRNA also co-localized with Map2a (a marker of dendrites) but not Tau1 (a
      marker of axons) in hippocampal neuronal cultures by in situ hybridization. In
      control rats, EAAC1 mRNA was observed in soma and proximal dendrites of
      hippocampal pyramidal neurons. Following pilocarpine- or kainate-induced
      seizures, EAAC1 mRNA was present in CA1 pyramidal cell dendrites up to 200MUm
      from the soma. These studies provide the first evidence that EAAC1 mRNA localizes
      to dendrites and suggest that dendritic targeting of EAAC1 mRNA is increased by
      seizure activity and may be regulated by neuronal activity/depolarization.

PMID- 21185904
TI  - Toxicological and immunomodulatory assessments of botryosphaeran (beta-glucan)
      produced by Botryosphaeria rhodina RCYU 30101.
AB  - Toxicological and immunomodulatory activities of botryosphaeran (BR), a newly
      emerged beta-glucan that comprises a beta-(1 -> 3) backbone and beta-(1 -> 6)
      branched glucose residues were assessed. BR was 1.82 * 10(6) Da (M.W.) estimated
      by reversely-linear equation constructed by regression of logarithms of standard
      polysaccharides and their retention times of gel permeation chromatography.
      Sprague-Dawley rats were daily gavage-administered with BR at doses of 0, 1.25,
      12.5, and 125 mg/kg body weight (BW) for 28 d. Serum hematological and
      biochemical analysis of all treatment were all within normal ranges. Mitogen
      stimulated lymphoblastogenesis of spleno-lymphocytes was enhanced by BR at doses
      of 1.25 and 12.5 mg/kg BW. Through in vitro comparative assessments, RAW 264.7
      macrophage (RAW) cells were treated with BR and two commercial beta-glucans,
      zymosan (ZY) and barley beta-glucan (GB), to characterize their relative
      immunomodulatory properties. All three beta-glucans stimulated phagocytosis on
      fluorescence-labeled Escherichia coli. At dose levels from 5 to 200 MUg/mL for
      24h, nitric oxide produced by BR- and ZY-treated cells were higher than those
      produced by GB-treated and control groups. BR, ZY but GB also stimulated RAW
      cells in producing TNF-alpha. The results demonstrate that BR is toxicologically
      accepted and features as a potent immunomodulator.

PMID- 21185903
TI  - Antipsychotic dose and diminished neural modulation: a multi-site fMRI study.
AB  - BACKGROUND: The effect of antipsychotics on the blood oxygen level dependent
      signal in schizophrenia is poorly understood. The purpose of the present
      investigation is to examine the effect of antipsychotic medication on independent
      neural networks during a motor task in a large, multi-site functional magnetic
      resonance imaging investigation. METHODS: Seventy-nine medicated patients with
      schizophrenia and 114 comparison subjects from the Mind Clinical Imaging
      Consortium database completed a paced, auditory motor task during functional
      magnetic resonance imaging (fMRI). Independent component analysis identified
      temporally cohesive but spatially distributed neural networks. The independent
      component analysis time course was regressed with a model time course of the
      experimental design. The resulting beta weights were evaluated for group
      comparisons and correlations with chlorpromazine equivalents. RESULTS: Group
      differences between patients and comparison subjects were evident in the cortical
      and subcortical motor networks, default mode networks, and attentional networks.
      The chlorpromazine equivalents correlated with the unimotor/bitemporal (rho=
      0.32, P=0.0039), motor/caudate (rho=-0.22, P=0.046), posterior default mode
      (rho=0.26, P=0.020), and anterior default mode networks (rho=0.24, P=0.03).
      Patients on typical antipsychotics also had less positive modulation of the
      motor/caudate network relative to patients on atypical antipsychotics
      (t(77)=2.01, P=0.048). CONCLUSION: The results suggest that antipsychotic dose
      diminishes neural activation in motor (cortical and subcortical) and default mode
      networks in patients with schizophrenia. The higher potency, typical
      antipsychotics also diminish positive modulation in subcortical motor networks.
      Antipsychotics may be a potential confound limiting interpretation of fMRI
      studies on the disease process in medicated patients with schizophrenia.

PMID- 21185905
TI  - Zirconia ceramic inlay-retained fixed dental prostheses - first clinical results
      with a new design.
AB  - OBJECTIVES: The purpose of this prospective study was to evaluate the clinical
      outcome of inlay-retained fixed dental prostheses (IRFDPs) with a new design made
      from a zirconia ceramic. METHODS: Twenty-three 3-unit IRFDPs were placed in 23
      patients, restoring five second premolars and 18 first molars. Preparations were
      performed in accordance with general principles for ceramic inlay restorations
      and modified with a retainer-wing bevel preparation in the enamel at the buccal
      and oral sides. The frameworks were scanned and milled out of zirconia ceramic,
      using the InLab CAD/CAM-system and the pontics were veneered with feldspathic
      ceramic. All IRFDPs were luted adhesively with composite resin. Clinical follow
      up examinations were performed annually. Statistical analysis was performed using
      descriptive statistics and Kaplan-Meier survival analysis. RESULTS: All patients
      with their 23 IRFDPs could be examined clinically after a mean observation time
      of 20 months. None of the IRFDPs failed. Two ceramic veneers fractured, both of
      them needed repair. One restoration debonded, but was recemented immediately.
      However, these technical complications did not affect the clinical function of
      the IRFDPs involved. CONCLUSIONS: The clinical outcome of zirconia ceramic IRFDPs
      with the modified design seems promising.

PMID- 21185906
TI  - Functional characterization of hematopoietic stem cells in the spleen.
AB  - OBJECTIVE: Hematopoietic stem cells (HSCs) reside in both bone marrow (BM) and
      spleen in adult mice. However, whether BM and spleen HSCs are functionally
      similar is not known. Spleen HSCs were compared with BM HSCs by various assays.
      MATERIALS AND METHODS: Whole BM and spleen cells were quantitatively analyzed by
      competitive repopulation. Single-cell transplantation was performed with HSCs
      purified from BM and spleen. A parabiosis model was used to distinguish organ
      specific HSCs from circulating HSCs. The cell cycle was analyzed with pyronin Y
      staining and bromodeoxyuridine uptake. RESULTS: Repopulating and self-renewal
      potentials were similar on a clonal basis between BM and spleen HSCs, whereas the
      HSC frequency in the spleen was significantly lower than that in the BM. Analysis
      of parabiotic mice suggested that most HSCs are long-term residents in each
      organ. Cell-cycle analysis revealed that spleen HSCs cycle twice as frequently as
      do BM HSCs, suggesting that G(0) phase length is longer in BM HSCs than in spleen
      HSCs. The cycling difference between BM and spleen HSCs was also observed in mice
      that had been reconstituted with BM or spleen cells, suggesting that HSC
      quiescence is regulated in an organ-specific manner. CONCLUSIONS: Spleen HSCs and
      BM HSCs are functionally similar, but their cycling behaviors differ.

PMID- 21185908
TI  - Immunolocalization of aquaporin-6 in the rat retina.
AB  - Previous RT-PCR experiments revealed that the neural retina of the rat contains
      gene transcripts of numerous aquaporins (AQPs), including AQP6 (Tenckhoff et al.,
      Neuroreport 16 (2005) 53-56). In the present study, we investigated the
      localization of AQP6 immunoreactivity in slices of the rat neural retina, and
      determined whether blue light injury of the retina affects the tissue
      distribution of this channel. AQP6 immunoreactivity was found to be selectively
      localized to the outer plexiform layer. Around the ribbon synapses in this layer,
      AQP6 labeling was co-localized with the glial water channel AQP4. AQP6 labeling
      was not colocalized with the marker of horizontal cells, calbindin, nor with the
      marker of rod bipolar cells, protein kinase Calpha. Along with the degeneration
      of photoreceptor cells after blue light treatment of the retina, AQP6-labeled
      ribbon synapses disappeared, and a punctate AQP6 staining redistributed into the
      inner nuclear layer. The co-localization of AQP6 and the glial water channel AQP4
      suggests a preferential localization of AQP6 in glial membranes that surround the
      ribbon synapses in the outer plexiform layer. AQP6 might be involved in the glia
      mediated osmo and ion regulation of the extracellular space in this layer.

PMID- 21185909
TI  - 17beta-estradiol and progesterone regulate multiple progestin signaling molecules
      in the anteroventral periventricular nucleus, ventromedial nucleus and sexually
      dimorphic nucleus of the preoptic area in female rats.
AB  - Recent work identified novel progestin signaling molecules, including
      progesterone receptor membrane component 1 (Pgrmc1), Pgrmc2, serpine mRNA binding
      protein 1 (Serbp1), progestin and adiponectin receptors 7 (Paqr7) and Paqr8.
      These molecules mediate rapid progesterone (P(4)) effects in non-neural tissue
      and we recently mapped their expression in the brain. Many rapid effects of P(4)
      require 17beta-estradiol (E(2)) and P(4) priming; therefore, we examined the
      effects of ovarian hormones on the expression of these non-classical progestin
      signaling molecules. We focused specifically on the anteroventral periventricular
      nucleus (AVPV), the sexually dimorphic nucleus of the preoptic area (SDN-POA) and
      the ventrolateral portion of the ventromedial nucleus (VMNvl). These brain nuclei
      are important for female reproduction. Ovariectomized adult female rats were
      implanted with capsules containing sesame oil or E(2), and injected 48 h later
      with sesame oil or P(4). Brains were collected 8 h later and RNA was isolated
      from the AVPV, SDN-POA and VMNvl. We assessed the effects of ovarian hormones on
      mRNA levels using quantitative polymerase chain reaction (QPCR). In the AVPV,
      Serbp1 mRNA levels were increased by P(4) in the presence of E(2), and Paqr8 was
      downregulated by P(4) alone. In the SDN-POA, combined E(2) and P(4) increased
      Pgrmc1 and Serbp1 mRNA levels, and E(2) alone increased Paqr8 mRNA levels.
      Finally, in the VMNvl, P(4) increased mRNA levels encoding Pgrmc1, Pgrmc2 and
      Serbp1, and the combination of E(2) and P(4) increased Pgrmc1 and Serbp1 mRNA
      levels. Paqr7 was not regulated by E(2) or P(4) in any brain region examined. In
      summary, we showed that ovarian hormones regulate novel progestin signaling
      molecules in brain regions important for the neuroendocrine control of
      reproduction.

PMID- 21185910
TI  - Repeated, intermittent exposures to diisopropylfluorophosphate in rats:
      protracted effects on cholinergic markers, nerve growth factor-related proteins,
      and cognitive function.
AB  - Organophosphates (OPs) pose a constant threat to human health due to their
      widespread use as pesticides and their potential employment in military and
      terrorist attacks. The acute toxicity of OPs has been extensively studied;
      however, the consequences of prolonged or repeated exposure to levels of OPs that
      produce no overt signs of acute toxicity (i.e. subthreshold levels) are poorly
      understood. Further, there is clinical evidence that such repeated exposures to
      OPs lead to prolonged deficits in cognition, although the mechanism for this
      effect is unknown. In this study, the behavioral and neurochemical effects of
      repeated, intermittent, and subthreshold exposures to the alkyl OP,
      diisopropylfluorophosphate (DFP) were investigated. Rats were injected with DFP
      s.c. (dose range, 0.25-1.0 mg/kg) every other day over the course of 30 days, and
      then given a 2 week, DFP-free washout period. In behavioral experiments conducted
      at various times during the washout period, dose dependent decrements in a water
      maze hidden platform task and a spontaneous novel object recognition (NOR)
      procedure were observed, while prepulse inhibition of the acoustic startle
      response was unaffected. There were modest decreases in open field locomotor
      activity and grip strength (particularly during the DFP exposure period);
      however, rotarod performance and water maze swim speeds were not affected. After
      washout, DFP concentrations were minimal in plasma and brain, however,
      cholinesterase inhibition was still detectable in the brain. Moreover, the 1.0
      mg/kg dose of DFP was associated with (brain region-dependent) alterations in
      nerve growth factor-related proteins and cholinergic markers. The results of this
      prospective animal study thus provide evidence to support two novel hypotheses:
      (1) that intermittent, subthreshold exposures to alkyl OPs can lead to protracted
      deficits in specific domains of cognition and (2) that such cognitive deficits
      may be related to persistent functional changes in brain neurotrophin and
      cholinergic pathways.

PMID- 21185911
TI  - Distal-less-like protein distribution in the larval lamprey forebrain.
AB  - A polyclonal antibody against the Drosophila distal-less (DLL) protein, cross
      reactive with cognate vertebrate proteins, was employed to map DLL-like
      expression in the midlarval lamprey forebrain. This work aimed to characterize in
      detail the separate diencephalic and telencephalic DLL expression domains, in
      order to test our previous modified definition of the lamprey prethalamus [Pombal
      and Puelles (1999) J Comp Neurol 414:391-422], adapt our earlier schema of
      prosomeric subdivisions in the lamprey forebrain to more recent versions of this
      model [Pombal et al. (2009) Brain Behav Evol 74:7-19] and reexamine the pallio
      subpallial regionalization of the lamprey telencephalon. We observed a large
      scale conservation of the topologic distribution of the DLL protein, in
      consonance with patterns of Dlx expression present in other vertebrates studied.
      Moreover, evidence was obtained of substantial numbers of DLL-positive neurons in
      the olfactory bulb and the cerebral hemispheres, in a pattern consistent with
      possible tangential migration out of the subpallium into the overlying pallium,
      as occurs in mammals, birds, frogs and teleost fishes.

PMID- 21185912
TI  - Effects of color information on face processing using event-related potentials
      and gamma oscillations.
AB  - In humans, face configuration, contour and color may affect face perception,
      which is important for social interactions. This study aimed to determine the
      effect of color information on face perception by measuring event-related
      potentials (ERPs) during the presentation of natural- and bluish-colored faces.
      Our results demonstrated that the amplitude of the N170 event-related potential,
      which correlates strongly with face processing, was higher in response to a
      bluish-colored face than to a natural-colored face. However, gamma-band activity
      was insensitive to the deviation from a natural face color. These results
      indicated that color information affects the N170 associated with a face
      detection mechanism, which suggests that face color is important for face
      detection.

PMID- 21185913
TI  - Neuroprotective effects of pioglitazone in a rat model of permanent focal
      cerebral ischemia are associated with peroxisome proliferator-activated receptor
      gamma-mediated suppression of nuclear factor-kappaB signaling pathway.
AB  - Previous studies have demonstrated that pioglitazone (Piog), a peroxisome
      proliferator-activated receptor gamma (PPARgamma) agonist, inhibits ischemia
      induced brain injury. Piog has also been shown to exert anti-inflammatory effects
      by attenuation of nuclear factor-kappaB (NF-kappaB) activation after myocardial
      ischemia/reperfusion injury. Because NF-kappaB is known to play a major role in
      the pathophysiology of brain ischemia, the present study was undertaken to
      elucidate whether pioglitazone attenuates ischemic neuronal damage through
      PPARgamma-mediated suppression of NF-kappaB apoptotic signaling pathway.
      Permanent middle cerebral artery occlusion (pMCAO) model was induced by using an
      intraluminal filament technique in rats. Piog was administrated i.p. twice (24 h
      before and at the time of ischemia insult) or once (10 min after ischemia). The
      neuroprotection of Piog was analyzed by assessing neurological deficits,
      infarction volume and morphological changes. The inhibition of NF-kappaB
      signaling pathway by Piog was evaluated by detecting the nuclear translocation of
      NF-kappaB p65 with immunohistochemistry and its target gene p53 by real-time PCR,
      and the expression of phospholated NF-kappaB p65 (p- NF-kappaB p65) in primary
      cultured neurons and the protein levels of IkappaBalpha and p-ERK in the ischemic
      cortex or striatum with Western blotting analysis. The contribution of a
      PPARgamma mechanism to Piog's inhibitory effects on NF-kappaB and neuroprotection
      was evaluated by pretreatment with the PPARgamma irreversible antagonist GW9662.
      In vitro ischemia in cultured primary neurons was induced by the oxygen-glucose
      deprivation (OGD) and the protective effect of Piog on cultured neurons was
      measured by lactate dehydrogenase (LDH) assay. Piog (0.5, 1, 2 mg/kg) reduced
      infarction volume, and improved morphological changes and motor deficits. Piog
      markedly up-regulated the protein levels of IkappaBalpha or p-ERK 6 h or 12 h
      after ischemia. Piog reduced the nuclear translocation of NF-kappaB p65 in the
      ischemic cortical cells and repressed the expression of p53 12 h after ischemia.
      Pre-treatment with GW9662 blocked Piog-elicited reduction in infarction volume,
      the increase in protein levels of IkappaBalpha and p-ERK, the reduction in the
      nuclear translocation of NF-kappaB subunit p65 and the repression of p53 mRNA
      expression. In addition, Piog attenuated the OGD-induced neuronal damage and
      inhibited the OGD-induced increases in p- NF-kappaB p65 in neurons. The present
      findings suggest that Piog's neuroprotection appears to be associated with
      PPARgamma-mediated suppression of NF-kappaB signaling pathway.

PMID- 21185914
TI  - Slow intrinsic oscillations in thick neocortical slices of hypoxia tolerant deep
      diving seals.
AB  - Direct evidence that the mammalian neocortex is an important generator of
      intrinsic activity comes from isolated neocortical slices that spontaneously
      generate multiple rhythms including those in the beta, delta and gamma range.
      These oscillations are also seen in intact animals where they interact with other
      areas including the hippocampus, thalamus and basal ganglia. Here we show that
      thick isolated neocortical slices from hooded seals intrinsically generate
      persistent spontaneous activities, both repetitive non-rhythmic activity with
      activity states lasting for several minutes, and oscillating activity with
      rhythms that are much slower (<0.1 Hz) than the rhythms previously described in
      vitro. These intrinsic activities were very robust and persisted for up to 1 h
      even in severely hypoxic conditions. We hypothesize that the remarkable hypoxia
      tolerance of the hooded seal nervous system made it possible to maintain
      functional integrity in slices thick enough to preserve intact neuronal networks
      capable of generating these slow oscillations. The observed activities in seal
      neocortical slices support the notion that mammalian cortical networks
      intrinsically generate multiple states of activity that include oscillatory
      activity all the way down to <0.1 Hz. This intrinsic neocortical excitability is
      an important contributor not only to sleep but also to the default awake state of
      the neocortex.

PMID- 21185916
TI  - The possible additional role of the cystic fibrosis transmembrane regulator to
      motoneuron inhibition produced by glycine effects.
AB  - In the present work we study the contribution of the chloride channel of the
      Cystic Fibrosis Transmembrane Regulator (CFTR) in the postsynaptic inhibition of
      somatic motoneurons during rapid-eye-movement (REM) sleep atonia. Postsynaptic
      inhibition of motoneurons is partially responsible for the atonia that occurs
      during REM sleep. Disfacilitation is an additional mechanism that lowers
      motoneuron excitability in this state. Postsynaptic inhibition is mediated by the
      release of glycine from synaptic terminals on motoneurons, and by GABA that plays
      a complementary role to that of glycine. In this work we look in brain stem
      motoneurons of neonatal rats at a mechanism unrelated to the actions of glycine,
      GABA or to disfacilitation which depends on the chloride channel of the CFTR. We
      studied the presence of CFTR by immunocytochemistry. In electrophysiological
      experiments utilizing whole cell recordings in in vitro slices we examined the
      consequences of blocking this chloride channel. The effects on motoneurons of the
      application of glycine, of the application of glibenclamide (a CFTR blocker) and
      again of glycine during the effects of glibenclamide were studied. Glycine
      produced an hyperpolarization, a decrease in motoneuron excitability and a
      decrease in input resistance, all characteristic changes of the postsynaptic
      inhibition produced by this neurotransmitter. Glibenclamide produced an increase
      in input resistance and in motoneurons' repetitive discharge as well as a shift
      in the equilibrium potential for chloride ions as indicated by the displacement
      of the reversal potential for glycinergic actions. In motoneurons treated with
      glibenclamide, glycine produced postsynaptic inhibition but this effect was
      smaller when compared to that elicited by glycine in control conditions. The fact
      that blocking of the CFTR-chloride channel in brain stem motoneurons influences
      glycinergic inhibition suggests that this channel may play a complementary role
      in the glycinergic inhibition that occurs during REM sleep.

PMID- 21185917
TI  - Cultured adult porcine astrocytes and microglia express functional interferon
      gamma receptors and exhibit toxicity towards SH-SY5Y cells.
AB  - In vitro cultures of various glial cell types are common systems used to model
      neuroinflammatory processes associated with age-dependent human neurodegenerative
      diseases. Even though most researchers choose to use neonatal rodent brain
      tissues as the source of glial cells, there are significant variations in glial
      cell functions that are species and age dependent. It has been established that
      human and swine immune systems have a number of similarities, which suggests that
      cultured porcine microglia and astrocytes may be good surrogates for human glial
      cell types. Here we describe a method that could be used to prepare more than 90%
      pure microglia and astrocyte cultures derived from adult porcine tissues. We
      demonstrate that both microglia and astrocytes derived from adult porcine brains
      express functional interferon-gamma receptors (IFN-gamma-R) and CD14. They become
      toxic towards SH-SY5Y neuroblastoma cells when exposed to proinflammatory
      mediators. Upon such stimulation with lipopolysaccharide (LPS) and interferon
      gamma (IFN-gamma), adult porcine microglia, but not astrocytes, secrete tumor
      necrosis factor-alpha (TNF-alpha) while both cell types do not secrete detectable
      levels of nitric oxide (NO). Comparison of our experimental data with previously
      published studies indicates that adult porcine glial cultures have certain
      functional characteristics that make them similar to human glial cells. Therefore
      adult porcine glial cells may be a useful model system for studies of human
      diseases associated with adulthood and advanced age. Adult porcine tissues are
      relatively easy to obtain in most countries and could be used as a reliable and
      inexpensive source of cultured cells.

PMID- 21185915
TI  - Photoperiodic suppression of drug reinstatement.
AB  - The rewarding influence of drugs of abuse varies with time of day and appears to
      involve interactions between the circadian and the mesocorticolimbic dopamine
      systems. The circadian system is also intimately involved in measuring daylength.
      Thus, the present study examined the impact of changing daylength (photoperiod)
      on cocaine-seeking behaviors. Male Sprague-Dawley rats were trained and tested on
      a 12L:12D light:dark schedule for cocaine-induced reinstatement of conditioned
      place preference (CPP) at three times of day (Zeitgeber time (ZT): 4, 12, and 20)
      to determine a preference score. Rats were then shifted to either shorter
      (6L:18D) or longer (18L:6D) photoperiods and then to constant conditions, re
      tested for cocaine-induced reinstatement under each different condition, and then
      returned to their original photoperiod (12L:12D) and tested once more. Rats
      exhibited a circadian profile of preference score in constant darkness with a
      peak at 12 h after lights-off. At both ZT4 and ZT20, but not at ZT12, shorter
      photoperiods profoundly suppressed cocaine reinstatement, which did not recover
      even after switching back to 12L:12D. In contrast, longer photoperiods did not
      alter reinstatement. Separate studies showed that the suppression of cocaine
      reinstatement was not due to repeated testing. In an additional experiment, we
      examined the photoperiodic regulation of tyrosine hydroxylase (TH) and dopamine
      transporter (DAT) proteins in drug-naive rats. These results revealed
      photoperiodic modulation of proteins in the prefrontal cortex and dorsal
      striatum, but not in the nucleus accumbens or ventral tegmental area. Together,
      these findings add further support to the circadian genesis of cocaine-seeking
      behaviors and demonstrate that drug-induced reinstatement is modulated by
      photoperiod. Furthermore, the results suggest that photoperiod partly contributes
      to the seasonal expression of certain drug-related behaviors in humans living at
      different latitudes and thus our findings may have implications for novel
      targeting of circadian rhythms in the treatment of addiction.

PMID- 21185918
TI  - Macrophage migration inhibitory factor contributes to development of nonsteroidal
      anti-inflammatory drugs-induced gastric injury in mice.
AB  - Macrophage migration inhibitory factor (MIF) plays an important role in the
      development of inflammation. In this study, we evaluated the role of MIF in
      gastric injury induced by non-steroidal anti-inflammatory drugs (NSAIDs) in mice.
      To induce gastric injury, mice were intraperitnoneally injected with 35 mg/kg of
      indomethacin. The level of MIF protein was up-regulated and severe gastric injury
      with inflammatory infiltrate was observed in the stomach of wild-type (WT) mice
      treated with indomethacin. The severity of gastric injury in MIF-deficient mice
      was less than that in WT mice. Increase in TNF-alpha in gastric tissue of mice
      treated with indomethacin was suppressed in MIF-deficient mice. The expression of
      HSP70, which has a cytoprotective role, was remarkably up-regulated in the
      stomach of MIF-deficient mice compared with WT mice after indomethacin treatment.
      Our results suggest that MIF is essential for the development of gastric injury
      induced by NSAIDs.

PMID- 21185919
TI  - Antitumor activity of extracts and compounds from the skin of the toad Bufo bufo
      gargarizans Cantor.
AB  - The skin of the toad Bufo bufo gargarizans Cantor is known to be rich in
      bufadienolides, peptides and alkaloids. It has been found to be a source of some
      extracts and biologically active compounds with antitumor activity. Cinobufacini
      (Huachansu), a Chinese medicine prepared from the dried toad skin, has been
      widely used in clinical therapy for various cancers in China. Bufadienolides,
      such as bufalin, cinobufagin, resibufogenin, and telocinobufagin, are the major
      active compounds derived from the toad skin. They are the maker biologically
      active compounds of cinobufagin while the antitumor activity of cinobufagin may
      be due to this kind of components. Experimental research has suggested that
      cinobufacini and its active compounds (e.g. bufalin and cinobufagin) exhibit
      significant antitumor activity, including inhibition of cell proliferation,
      induction of cell differentiation, induction of apoptosis, disruption of the cell
      cycle, inhibition of cancer angiogenesis, reversal of multi-drug resistance, and
      regulation of the immune response. Clinical data have indicated that cinobufacini
      may have effective anticancer activity with low toxicity and few side effects.
      Data to date suggest it may also enhance quality of life for patients with
      cancer. Thus, this review briefly summarizes recent studies on the anticancer
      activity of cinobufacini and some of its active compounds from the skin of the
      toad Bufo bufo gargarizans Cantor. This might provide additional evidence for
      further study of the extracts and active compounds from the toad skin in cancer
      treatment.

PMID- 21185920
TI  - Pharmacological studies in an herbal drug combination of St. John's Wort
      (Hypericum perforatum) and passion flower (Passiflora incarnata): in vitro and in
      vivo evidence of synergy between Hypericum and Passiflora in antidepressant
      pharmacological models.
AB  - Extracts of Hypericum, Passiflora and Valeriana are used for the treatment of
      mild depression and anxiety. We were interested whether a combination of
      Hypericum and Passiflora exerts comparable effects to Hypericum alone. We used
      two well-established models for investigating extracts for their anti-depressant
      activity, namely the effects on synaptic uptake of serotonin and the forced
      swimming-test. We show here for the first time, that Passiflora significantly
      enhances the pharmacological potency of Hypericum in both models. Our data
      suggest that anti-depressive therapeutic effects of Hypericum are possible with
      lower doses, when it is combined with Passiflora, than with mono-preparations of
      Hypericum.

PMID- 21185921
TI  - Comparative pharmacokinetics of paeoniflorin in plasma of vascular dementia and
      normal rats orally administrated with Danggui-Shaoyao-San or pure paeoniflorin.
AB  - Danggui-Shaoyao-San (DSS), a traditional Chinese medicinal prescription, is
      clinically used for the treatment of vascular dementia (VD). This study compared
      the pharmacokinetics of paeoniflorin, the main active ingredients in Paeonia
      lactiflora Pall, in VD and normal rats administrated with DSS or pure
      paeoniflorin. The absorptions of paeoniflorin in both VD and normal group of rats
      were better when orally administrated with DSS than that with pure paeoniflorin,
      which justified the combined use as formula DSS. Moreover, a better absorption of
      paeoniflorin in rats of the VD than in normal group was observed, which is
      helpful for the treatment of VD.

PMID- 21185922
TI  - Hepatoprotective and TNF-alpha inhibitory activity of Zosima absinthifolia
      extracts and coumarins.
AB  - Zosima absinthifolia (ZA) extracts and the coumarins (+)-columbianadin and (-)
      deltoin were evaluated for their potential hepatoprotective and antiinflamatory
      effects in a CCl(4)-induced hepatotoxicity assay in rats and by the inhibition of
      TNF-alpha production on LPS-stimulated THP-1 macrophages, respectively. Both the
      ZA extracts and the coumarins showed hepatoprotective activity confirmed by
      monitoring the ALT/AST levels and by histopathological examination. The
      antiinflamatory activity, proved by the inhibition of TNF-alpha production, was
      found to be higher for the n-hexane root extract than for coumarins, suggesting
      synergic potential of the extract. The concentration of (-)-deltoin and (+)
      columbianadin in extracts was determined by HPLC analysis.

PMID- 21185923
TI  - Macrostachyols A-D, new oligostilbenoids from the roots of Gnetum macrostachyum.
AB  - Four new oligostilbenes, macrostachyols A-D (1-4) along with six known
      stilbenoids (5-10), were isolated from the roots of Gnetum macrostachyum. These
      compounds were also evaluated for their cytotoxicity towards HeLa and KB cell
      lines. Only compound 4 showed the significant cytotoxicity to HeLa cells with
      IC(50) value of 4.13 MUM.

PMID- 21185924
TI  - Evolutionary patterns of killer cell Ig-like receptor genes in Old World monkeys.
AB  - Killer cell Ig-like receptors (KIRs) modulate the cytotoxic effects of Natural
      Killer cells. KIR genes are encoded in the Leucocyte Receptor Complex and are
      characterized by their high haplotypic diversity and polymorphism. The KIR system
      has been studied in only three species of Old World monkeys, the rhesus macaque,
      the cynomolgus macaque, and the sabaeus monkey, displaying a complexity rivaling
      that of hominids (human and apes). Here we analyzed bacterial artificial
      chromosome draft sequences spanning the KIR haplotype of three other Old World
      monkeys, the vervet monkey (Chlorocebus aethiops), the olive baboon (Papio
      anubis) and the colobus monkey (Colobus guereza). A total of 25 KIR gene models
      were identified in these species, predicted to encode receptors with 1, 2, and 3
      extracellular Ig domains, all of them with long cytoplasmic domains having two
      putative ITIMs, although three had a positively charged residue in the
      transmembrane domain. Sequence and phylogenetic analyses showed that most Old
      World monkeys shared five classes of KIR loci: i) KIR2DL5/3DL20 in the most
      centromeric region, followed by ii) the single Ig domain-encoding locus KIR1D,
      iii) the pseudogene KIR2DP, iv) the conserved KIR2DL4, and v) the highly
      diversified KIR3DL/H loci in the telomeric half of the cluster. An exception to
      this pattern was the KIR haplotype of the colobus monkey that lacked the KIR1D,
      KIR2DP, and KIR2DL4 loci of the central region of the cluster. Thus, Old World
      monkeys display a broad spectrum of KIR haplotype variation that has been
      generated upon an ancestral haplotype architecture by gene duplication, gene
      deletion, and non-homologous recombination.

PMID- 21185925
TI  - NP-647, a novel TRH analogue: investigating physicochemical parameters critical
      for its oral and parenteral delivery.
AB  - NP-647 (L-pGlu-(2-propyl)-L-His-L-ProNH(2)) is a novel thyrotropin releasing
      hormone (TRH) analogue, with potential antiepileptic activity. In the present
      study, the physicochemical parameters of NP-647, including its solid state
      properties, dissociation constant, partition coefficient, solubility (intrinsic
      solubility and pH-solubility profile) and stability (gastrointestinal enzymatic
      stability, pH-stability profile and temperature stability) were investigated for
      their criticality for oral and parenteral delivery. NP-647 was characterized as
      amorphous material having glass transition temperature of 66.73  degrees C at 50%
      RH. It was found very hygroscopic with deliquescent in nature. pK(a) of the
      compound, as determined using potentiometric titration, was found to be 7.2 +/-
      0.02 (basic). Intrinsic solubility and pH-solubility behavior were determined
      using dissolution titration template method. NP-647 has intrinsic solubility of
      2.4 +/- 0.01 mg mL(-1). Partition/distribution studies indicate that NP-647 has a
      low log P (-1.07 +/- 0.06) and log D(7.4) (-1.20 +/- 0.02), characteristic of
      hydrophilic molecule. It was found most stable in tartrate buffer of pH of 5.0.
      Arrhenius plot of NP-647 suggest its half life of ~ 3.2 years and shelf life of ~
      6 months. These studies conclude that amorphous nature of NP-647 with
      deliquescent property will be critical in its solid oral dosage formulation and
      need to be investigated further.

PMID- 21185926
TI  - Physical stability of nanosuspensions: investigation of the role of stabilizers
      on Ostwald ripening.
AB  - The effect of stabilizer type (small molecule vs. polymeric) and the amount of
      micellar solubilized drug on Ostwald ripening of nanosuspensions was
      investigated. Indomethacin nanosuspensions were prepared with small molecule
      stabilizers (sodium lauryl sulfate (SLS) and Dowfax 2A1 (DF)) and a polymeric
      stabilizer (hydroxypropyl methyl cellulose (HPMC)). Two different drug:stabilizer
      ratios were used to evaluate the effect of micellar solubilized drug. The Ostwald
      ripening potential of nanosuspensions was evaluated by subjecting them to various
      stress conditions (temperature (15, 25, 35 and 45 degrees C), thermal cycling,
      and mechanical shaking) for three months. The mean particle size increased in all
      SLS and DF formulations stored under different stress conditions. No effect of
      micellar solubilized drug on the Ostwald ripening rate was observed. In the case
      of HPMC formulations only those stored at higher temperatures (35 or 45 degrees
      C) exhibited an increase in mean particle size. The increase in size in the HPMC
      formulation stored at 45 degrees C was attributed to dehydration of the HPMC
      chains and subsequent loss of protection of the nanoparticles. The cube of the
      mean particle diameter versus time plot was determined to be non-linear for all
      formulations exhibiting Ostwald ripening. Therefore, according to the Lifshitz,
      Slyozov and Wagner theory the process was not diffusion controlled. The most
      probable mechanism for Ostwald ripening was surface nucleation controlled.

PMID- 21185927
TI  - Lipid membrane composition influences drug release from
      dioleoylphosphatidylethanolamine-based liposomes on exposure to ultrasound.
AB  - The effect of membrane composition on calcein release from
      dioleoylphosphatidylethanolamine (DOPE)-based liposomes on exposure to low doses
      of 1.13 MHz focused ultrasound (US) was investigated by multivariate analysis,
      with the goal of designing liposomes for US-mediated drug delivery. Regression
      analysis revealed a strong correlation between sonosensitivity and the non
      bilayer forming lipids DOPE and pegylated distearoylphosphatidylethanolamine
      (DSPE-PEG 2000), with DOPE having the strongest impact. Unlike most of the
      previously studied distearoylphosphatidylethanolamine (DSPE)-based liposomes, all
      the current DOPE-based liposome formulations were found stable in 20% serum in
      terms of drug retention.

PMID- 21185928
TI  - Physiological differences between histologically defined subdivisions in the
      mouse auditory thalamus.
AB  - The auditory thalamic area includes the medial geniculate body (MGB) and the
      lateral part of the posterior thalamic nucleus (Pol). The MGB can be subdivided
      into a ventral subdivision, forming part of the lemniscal (primary) auditory
      pathway, and medial and dorsal subdivisions, traditionally considered (alongside
      the Pol) part of the non-lemniscal (secondary) pathway. However, physiological
      studies of the auditory thalamus have suggested that the Pol may be more
      appropriately characterised as part of the lemniscal pathway, while the medial
      MGB may be part of a third (polysensory) pathway, with characteristics of
      lemniscal and non-lemniscal areas. We document physiological properties of
      neurons in histologically identified areas of the MGB and Pol in the
      anaesthetised mouse, and present evidence in favour of a distinctive role for
      medial MGB in central auditory processing. In particular, medial MGB contains a
      greater proportion of neurons with short first-spike latencies and high response
      probabilities than either the ventral or dorsal MGB, despite having low
      spontaneous rates. Therefore, medial MGB neurons appear to fire more reliably in
      response to auditory input than neurons in even the lemniscal, ventral
      subdivision. Additionally, responses in the Pol are more similar to those in the
      ventral MGB than the dorsal MGB.

PMID- 21185929
TI  - Polygenic inheritance of sensorineural hearing loss (Snhl2, -3, and -4) and organ
      of Corti patterning defect in the ALR/LtJ mouse strain.
AB  - Progressive sensorineural hearing loss in humans is a common and debilitating
      impairment. Sensorineural deafness in inbred strains of mice is a similarly
      common and genetically diverse phenotype providing experimental models to study
      the underlying genetics and the biological effects of the risk factors. Here, we
      report that ALR/LtJ mice develop early-onset profound sensorineural hearing loss
      as evidenced by high-to-low frequency hearing threshold shifts, absent distortion
      product otoacoustic emissions, and normal endocochlear potentials. Linkage
      analyses of a segregating backcross revealed three novel quantitative trait loci
      named sensorineural hearing loss (Snhl) -2, -3, and -4. The QTLs achieved very
      high LOD scores with markers on chromosome 1 (Snhl2, LOD: 12), chromosome 6
      (Snhl3, LOD: 24) and chromosome 10 (Snhl4, LOD: 11). Together, they explained 90%
      of the phenotypic variance. While Snhl2 and Snhl3 affected hearing thresholds
      across a broad range of test frequencies, Snhl4 caused primarily high-frequency
      hearing loss. The hearing impairment is accompanied by an organ of Corti
      patterning defect that is characterized by the ectopic expression of
      supernumerary outer hair cells organized in rows along the abneural site of the
      sensory epithelium in the presence of unaltered planar polarity and otherwise
      normal cochlear duct morphology. Cloning the Snhl2, -3, and -4 genes in the
      ALR/LtJ mice may provide important genetic and mechanistic insights into the
      pathology of human progressive sensorineural deafness.

PMID- 21185930
TI  - Antinociceptive effect of extract of Emilia sonchifolia in mice.
AB  - AIM OF THE STUDY: Emilia sonchifolia (L.) DC. (Asteraceae) is a medicinal plant
      traditionally used in Brazilian folk medicine to treat asthma, fever, cuts,
      wounds and rheumatism. This study was conducted to establish the antinociceptive
      properties of hydroethanolic extract from aerial parts of Emilia sonchifolia in
      mice using chemical and thermal models of nociception. MATERIALS AND METHODS: To
      evaluate the antinociceptive effect of Emilia sonchifolia hydroethanolic extract
      (EsHE) administered by oral route, peripheral (acetic acid-induced abdominal
      writhing and formalin), spinal (tail flick) and supra-spinal (hot plate)
      behavioral models of acute pain were used. High-performance liquid chromatography
      (HPLC) was used to determine the fingerprint chromatogram of the EsHE. RESULTS:
      The EsHE at test doses of 100 and 300 mg/kg, p.o. clearly demonstrated
      antinociceptive activity in all tests. The extract had a stronger antinociceptive
      effect than morphine. Administration of the opioid receptor antagonist, naloxone,
      completely inhibited the antinociceptive effect induced by EsHE (100mg/kg). The
      presence of phenolic compounds in the extract of Emilia sonchifolia was confirmed
      using HPLC. CONCLUSION: The extract of Emilia sonchifolia markedly exhibits
      opioid-mediated anti-nociceptive activity action in mice. Thus, may be useful in
      the treatment of inflammatory hyperalgesic disorders, which supports previous
      claims of its traditional use.

PMID- 21185931
TI  - Diuretic activity and acute oral toxicity of Palicourea coriacea (Cham.) K Schum.
AB  - AIM OF THE STUDY: Palicourea coriacea (Cham.) K Schum, is an endemic plant used
      in the Midwestern Region of Brazil, popularly known as "douradinha do campo" and
      "congonha do campo". This plant has been used in traditional medicine for several
      ailments, especially to treat kidney diseases. Since no formal studies on the
      biological activities and medicinal properties of the ethanolic extract of
      Palicourea coriacea (PCEE) have been carried out previously, the present study
      represents the first research into the efficacy of this plant as a diuretic agent
      employing laboratory rats as test animals. MATERIALS AND METHODS: For diuretic
      activity evaluation we assayed three doses of PCEE (20, 40 and 80mg/kg) and
      measurement of the urinary volume and electrolytes (Na(+), K(+)) concentration
      were taken. The acute oral toxicity of PCEE was investigated according to OECD
      Guideline 423. RESULTS: The oral administration of a single dose of PCEE
      significantly increased the urinary volume in 24h. Additionally, the treatment
      with PCEE increased, in a dose-dependent manner, the excretion of both, Na(+) and
      K(+). No sign of toxicity was observed in the animals. CONCLUSIONS: The present
      study confirmed the ethnopharmacological use of Palicourea coriacea as a diuretic
      agent in the experimental condition tested here. Additionally, this work supports
      the importance of the preservation of local knowledge as well as the conservation
      of Brazilian biodiversity.

PMID- 21185933
TI  - Meta-analysis of MTHFR gene variants in schizophrenia, bipolar disorder and
      unipolar depressive disorder: evidence for a common genetic vulnerability?
AB  - Past analyses examining the relationship between genetic variation in the 5, 10
      methylenetetrahydrofolate reductase (MTHFR) gene and psychiatric disorders have
      provided mixed and largely inconclusive findings. MTHFR is involved in the one
      carbon metabolic pathway which is essential for DNA biosynthesis and the
      epigenetic process of DNA methylation. We conducted a meta-analysis of all
      published case-control studies investigating associations between two common
      MTHFR single nucleotide polymorphisms (SNPs), MTHFR C677T (sample size 29,502)
      and A1298C (sample size 7934), and the major psychiatric disorders (i)
      schizophrenia (SZ), (ii) bipolar disorder (BPD), and (iii) unipolar depressive
      disorder (UDD). In order to examine possible shared genetic vulnerability, we
      also tested for associations between MTHFR and all of these major psychiatric
      disorders (SZ, BPD and UDD) combined. MTHFR C677T was significantly associated
      with all of the combined psychiatric disorders (SZ, BPD and UDD); random effects
      odds ratio (OR)=1.26 for TT versus CC genotype carriers; confidence interval (CI)
      1.09-1.46); meta-regression did not suggest moderating effects of psychiatric
      diagnosis, sex, ethnic group or year of publication. Although MTHFR A1298C was
      not significantly associated with the combination of major psychiatric disorders,
      nor with SZ, there was evidence for diagnostic moderation indicating a
      significant association with BPD (random effects OR=2.03 for AA versus CC
      genotype carriers, CI: 1.07-3.86). Meta-analysis on UDD was not possible due to
      the small number of studies available. This study provides evidence for shared
      genetic vulnerability for SZ, BPD and UDD mediated by MTHFR 677TT genotype, which
      is in line with epigenetic involvement in the pathophysiology of these
      psychiatric disorders.

PMID- 21185932
TI  - Antihypertensive effects of isoquercitrin and extracts from Tropaeolum majus L.:
      evidence for the inhibition of angiotensin converting enzyme.
AB  - AIM OF THE STUDY: Previous studies have shown that the extracts obtained from
      Tropaeolum majus L. exhibit pronounced diuretic properties. In the present study,
      we assessed whether the hypotensive and/or antihypertensive mechanism of
      hydroethanolic extract (HETM), semi-purified fraction (TMLR) obtained from T.
      majus and the flavonoids isoquercitrin (ISQ) and kaempferol (KPF) can be mediated
      by their interaction with angiotensin converting enzyme (ACE). METHODS AND
      METHODS: Firstly, to evaluate changes in mean arterial pressure (MAP), different
      groups of normotensive and spontaneously hypertensive rats (SHR) were orally and
      intraduodenally treated with HETM (10-300 mg/kg) and TMLR (12.5-100mg/kg) and
      intravenously treated with ISQ and KPF being later anesthetized with ketamine
      (100mg/kg) and xylazine (20mg/kg). The left femoral vein and the right carotid
      artery were isolated, and polyethylene catheters were inserted for ISQ and KPF
      (0.5-4 mg/kg) administration and blood pressure recording, respectively. The
      plasmatic ACE activity was evaluated to indirect fluorimetry, in serum samples
      after orally treatment with HETM, TMLR, ISQ and KPF. RESULTS: The oral
      administration of the HETM and its TMLR significantly reduced, in a dose
      dependent manner, the MAP in both normotensive and SHR. In addition, these
      preparations significantly decreased the MAP for up to 3h after the
      administration of the extract. Additionally, the intravenous administration of
      ISQ, but not KPF, decreased MAP in rats. Otherwise, neither the extracts nor ISQ
      affected the heart rate. The oral administration of the HETM, TMLR or ISQ reduced
      ACE activity in serum samples at 90 min after administration. Finally, the
      intravenous administration of ISQ caused a significant reduction in the
      hypertensive response to angiotensin I, but not angiotensin II in normotensive
      rats. CONCLUSION: Our results show that the hypotensive effects caused by the
      HETM, as well as by its TMLR, may be associated with the high levels of the
      flavonoid ISQ found in this plant. In addition, ISQ-induced hypotension in rats
      is an event dependent on the inhibition of angiotensin II generation by ACE.

PMID- 21185934
TI  - Regulation of iron pathways in response to hypoxia.
AB  - Constituting an integral part of a heme's porphyrin ring, iron is essential for
      supplying cells and tissues with oxygen. Given tight links between oxygen
      delivery and iron availability, it is not surprising that iron deprivation and
      oxygen deprivation (hypoxia) have very similar consequences at the molecular
      level. Under hypoxia, the expression of major iron homeostasis genes including
      transferrin, transferrin receptor, ceruloplasmin, and heme oxygenase-1 is
      activated by hypoxia-inducible factors to provide increased iron availability for
      erythropoiesis in an attempt to enhance oxygen uptake and delivery to hypoxic
      cells. Iron-response proteins (IRP1 and IRP2) and "cap-n-collar" bZIP
      transcriptional factors (NE-F2 p45; Nrf1, 2, and 3; Bach1 and 2) also control
      gene and protein expression of the key iron homeostasis proteins. In this
      article, we give an overview of the mechanisms by which iron pathways are
      regulated by hypoxia at multiple levels. In addition, potential clinical benefits
      of manipulating iron pathways in the hypoxia-related conditions anemia and
      ischemia are discussed.

PMID- 21185936
TI  - Workshop/conference report on EMA draft guideline on validation of bioanalytical
      methods.
AB  - This is a summary report of the workshop on the EMA Draft Guideline on Validation
      of Bioanalytical Methods held April 15-16th 2010 in Brussels (Belgium) and
      jointly organised by the European Bioanalysis Forum (EBF) and the European
      Federation for Pharmaceutical Sciences (EUFEPS). Aim of the workshop was to
      discuss the current scientific knowledge in the area of bioanalysis, the
      regulatory requirements with special focus on the new Draft Guideline and their
      subsequent implementation to the work in bioanalytical laboratories. Comments on
      the Draft Guideline were presented and discussed with representatives from
      regulatory authorities in Europe. The workshop started with discussions on the
      scope of the Guideline and the need for implementation of GLP. A special focus
      was set on method validation of chromatographic procedures and subsequent study
      sample analysis. In addition, requirements for ligand-binding assays were briefly
      addressed. Intention of this Conference Report is to summarise important aspects
      of the discussions in order to draw certain conclusions, and to identify points
      which remain open and may require clarification at a later stage.

PMID- 21185935
TI  - Exercise training attenuates oxidative stress and decreases p53 protein content
      in skeletal muscle of type 2 diabetic Goto-Kakizaki rats.
AB  - Oxidative stress can impair mitochondrial function and fuel utilization and is
      closely linked with the development of insulin resistance in skeletal muscle in
      diabetes mellitus as well as fatty liver disease. In vitro data indicate that
      cellular levels of reactive oxygen species depend on the expression and activity
      of p53, which plays a key role in energy metabolism and as a crucial
      transcription factor for SCO cytochrome oxidase deficient homolog 2 (SCO2) and
      tumor p53-induced glycolysis and apoptosis regulator (TIGAR), which regulate
      mitochondrial respiration and glycolysis in cells. The aims of this study were:
      (1) to investigate whether exercise training could attenuate the development of
      oxidative stress in skeletal muscle in rats with diabetes mellitus (DM) and (2)
      to evaluate the potential role of p53 and its transcriptional targets in exercise
      induced mitochondrial adaptation in skeletal muscle in rats with DM. Goto
      Kakizaki (GK) rats, which develop type 2 DM (T2DM) early in life, were randomly
      divided into two groups: (1) subjected to regular exercise on a treadmill at
      20m/min for 30-60min, 6 days per week for 8 weeks (GK exercising, n=7), and (2)
      rested controls (GK control, n=7). Exercise training increased serum adiponectin
      and decreased serum insulin and levels of glycosylated hemoglobin (P<0.05).
      Skeletal muscle GSH content and GSH:GSSG ratio increased in GK exercising rats vs
      GK controls (P<0.05). Skeletal muscle COX activity (P<0.05), mtDNA markers
      (P<0.01), and COXII protein levels (P<0.05) increased in response to exercise
      training. Exercise training decreased p53 protein levels and TIGAR expression in
      skeletal muscle (P<0.05), but SCO2 expression was unchanged. These data indicate
      that exercise training can attenuate oxidative stress and increase mitochondrial
      DNA content in skeletal muscle in rats with T2DM and that exercise-induced
      suppression of p53 and TIGAR expression may play a role in preventing oxidative
      stress in insulin resistance.

PMID- 21185937
TI  - Detection of antibodies against HLA-C epitopes in patients with rejected kidney
      transplants.
AB  - BACKGROUND: Although HLA-C matching is not considered in kidney transplantation,
      several reports have shown that anti-HLA-C antibodies are associated with
      rejection and graft failure. DNA-based typing methods can now accurately
      determine HLA-C compatibility and sensitive assays such as Luminex with single
      alleles can identify HLA-C antibodies. HLA-C displays considerable amino acid
      polymorphism that can be translated into a structurally defined epitope
      repertoire. METHODS: We have analyzed post-allograft nephrectomy sera from 45 HLA
      C mismatched cases submitted by 15 laboratories worldwide participating in the
      15th International Histocompatibility Workshop. All of them had HLA class I
      antibodies detected by a Luminex-based solid phase method using single-allele
      beads. This study addressed the determination of antibodies against donor HLA-C
      mismatches. Analysis of antibody reactivity patterns was performed using
      HLAMatchmaker, a structurally based matching program that considers 56 HLA-C
      eplets to define antibody-reactive epitopes. Many eplets shared by groups of HLA
      C antigens, whereas others are also shared with HLA-A and/or HLA-B antigens.
      RESULTS: Twenty-seven patients (60%) had donor-specific HLA-C antibodies,
      significantly less than the donor-specific antibodies induced by HLA-A and HLA-B
      mismatches. HLA-C antibody responses correlated with the eplet loads of the HLA-C
      mismatches. There were 352 instances whereby a donor HLA-C eplet was mismatched
      and for 84 (24%) of them there was antibody reactivity with a particular eplet
      (69 instances) or an eplet pair (15 instances). The latter generally consisted of
      mismatched eplets paired with self-eplets shared between the immunizing HLA-C
      alleles and HLA alleles of the patient. Several HLA-C eplets exhibited a
      relatively high immunogenicity as evidenced by their frequencies of specific
      antibodies. CONCLUSION: These findings demonstrate the importance of HLA-C
      mismatching in humoral sensitization and that HLA-C epitopes can induce specific
      antibodies. They illustrate the usefulness of HLAMatchmaker in understanding
      donor-specific antibody reactivity patterns and the determination of HLA mismatch
      acceptability when transplantation is considered.

PMID- 21185938
TI  - Intramuscular delivery of a naked DNA plasmid encoding proinsulin and pancreatic
      regenerating III protein ameliorates type 1 diabetes mellitus.
AB  - Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by
      inflammation of pancreatic islets and destruction of beta cells. Up to now, there
      is still no cure for this devastating disease and alternative approach should be
      developed. To explore a novel gene therapy strategy combining immunotherapy and
      beta cell regeneration, we constructed a non-viral plasmid encoding proinsulin
      (PI) and pancreatic regenerating (Reg) III protein (pReg/PI). Therapeutic
      potentials of this plasmid for T1DM were investigated. Intramuscular delivery of
      pReg/PI resulted in a significant reduction in hyperglycemia and diabetes
      incidence, with an increased insulin contents in the serum of T1DM mice model
      induced by STZ. Treatment with pReg/PI also restored the balance of Th1/Th2
      cytokines and expanded CD4(+)CD25(+)Foxp3(+) T regulatory cells, which may
      attribute to the establishment of self-immune tolerance. Additionally, in
      comparison to the mice treated with empty vector pBudCE4.1 (pBud), attenuated
      insulitis and apoptosis achieved by inhibiting activation of NF-kappaB in the
      pancreas of pReg/PI treated mice were observed. In summary, these results
      indicate that intramuscular delivery of pReg/PI distinctly ameliorated STZ
      induced T1DM by reconstructing the immunological self-tolerance and promoting the
      regeneration of beta cells, which might be served as a promising candidate for
      the gene therapy of T1DM.

PMID- 21185940
TI  - The RhoGAP domain-containing protein, Porf-2, inhibits proliferation and enhances
      apoptosis in neural stem cells.
AB  - Neural stem cells (NSCs) are essential to developing and mature CNS. They shape
      the structural and functional layouts of the brain in developing CNS and continue
      to proliferate, generating new neurons in several adult brain regions. Preoptic
      regulatory factor-2 (Porf-2), a RhoGAP domain-containing protein expressed in
      CNS, has a role in gender-related brain development and function. Porf-2
      expression was knocked down in C17.2, a mouse cerebellar multipotent cell line.
      This increased proliferation and decreased drug-induced apoptosis without
      affecting cell type distribution following differentiation induction. It lowered
      levels of cyclin kinase inhibitor p21, affected G1 to S phase cell cycle
      transition; partially blocked the elevation in p53 transcriptional activity, p21
      and Bcl-2-associated X protein (Bax) levels caused by bleomycin, but had no
      influence on enhancement of Bax in response to staurosporine. Thus Porf-2 may
      inhibit NSC proliferation by enhancing p21 protein levels followed by G1 phase
      arrest; it plays pro-apoptotic roles in response to drug treatment through both
      p53 transcription-dependent and independent pathways. This is consistent with
      categorization of Porf-2 as a functional RhoGAP in CNS.

PMID- 21185941
TI  - Evaluation of housekeeping genes as references for quantitative real time RT-PCR
      analysis of gene expression in Japanese flounder (Paralichthys olivaceus).
AB  - Japanese flounder (Paralichthys olivaceus) is an important economic fish species
      cultured worldwide. In this report, we compared the potentials of ten
      housekeeping genes as quantitative real time RT-PCR (qRT-PCR) references for the
      study of gene expression in Japanese flounder under normal physiological
      conditions and during bacterial infection. For this purpose, the expression of
      the ten genes in eight flounder tissues (liver, spleen, kidney, heart, muscle,
      brain, gill, and intestine) was determined by qRT-PCR before and after bacterial
      infection. The expression levels of the housekeeping genes were then compared and
      evaluated with geNorm and NormFinder algorithms. The results showed that before
      bacterial infection, the tested genes exhibited tissue-specific expressions to
      various degrees, with beta-actin and ubiquitin-conjugating enzyme being ranked as
      the most stable genes across tissue types. Following bacterial challenge, all the
      tested genes varied in expression levels in tissue-dependent manners and no cross
      all-tissue type reference gene was identified among the examined panel of
      housekeeping genes; however, alpha-tubulin was recognized as the most stable gene
      in four (spleen, heart, muscle, and gill) of the eight examined tissues. These
      results indicate that for qRT-PCR analysis of gene expression in Japanese
      flounder as a function of bacterial infection, the choice of reference genes
      should be made according to tissue type.

PMID- 21185939
TI  - NFAT regulates pre-synaptic development and activity-dependent plasticity in
      Drosophila.
AB  - The calcium-regulated transcription factor NFAT is emerging as a key regulator of
      neuronal development and plasticity but precise cellular consequences of NFAT
      function remain poorly understood. Here, we report that the single Drosophila
      NFAT homolog is widely expressed in the nervous system including motor neurons
      and unexpectedly controls neural excitability. Likely due to this effect on
      excitability, NFAT regulates overall larval locomotion and both chronic and acute
      forms of activity-dependent plasticity at the larval glutamatergic neuro-muscular
      synapse. Specifically, NFAT-dependent synaptic phenotypes include changes in the
      number of pre-synaptic boutons, stable modifications in synaptic microtubule
      architecture and pre-synaptic transmitter release, while no evidence is found for
      synaptic retraction or alterations in the level of the synaptic cell adhesion
      molecule FasII. We propose that NFAT regulates pre-synaptic development and
      constrains long-term plasticity by dampening neuronal excitability.

PMID- 21185942
TI  - Immunostimulant effects of Cotinus coggyria on rainbow trout (Oncorhynchus
      mykiss).
AB  - In this study, non-specific immune effects of tetra (Cotinus coggyria) on rainbow
      trout (Oncorhynchus mykiss) by dietary intake were investigated. Fish were fed
      daily ad libitum with diets containing 0.5% and 1.0% tetra for 3 weeks. After
      this period, fish were switched back to the basal diet for additional 6 weeks.
      Extracellular and intracellular respiratory burst activities, phagocytosis in
      blood leukocytes, lysozyme activities, and total plasma protein levels were
      evaluated at the end of the tetra feeding period and every 3 weeks during the
      basal diet period. Extracellular and intracellular respiratory burst activities,
      phagocytic activity, lysozyme activity and total protein level parameters of the
      groups containing 0.5% and 1.0% tetra were higher than the control group at the
      end of the 3rd, 6th and 9th weeks, respectively (P < 0.05). The highest values of
      the non-specific immune parameters were observed in the group fed with 1.0%
      tetra. Tetra groups did not show any significant difference (P > 0.05) in terms
      of specific growth rate and average weight of the fish.

PMID- 21185943
TI  - Non-invasive diffusion tensor imaging detects white matter degeneration in the
      spinal cord of a mouse model of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is characterized by selective degeneration of
      motor neurons. Here we examine the ability of magnetic resonance imaging (MRI) to
      measure axonal degeneration in the lumbar spinal cord of the SOD1 mouse model of
      ALS. Diffusion tensor imaging (DTI) was successful in detecting axonal spinal
      cord damage in vivo. Fractional anisotropy (FA) values were reduced exclusively
      in the ventral white matter tracts of the lumbar spinal cord of ALS-affected SOD1
      mice compared to wild-type littermates, with this effect becoming more pronounced
      with disease progression. The reduced FA values were therefore limited to white
      matter tracts arising from the motor neurons, whereas sensory white matter fibers
      were preserved. Significant decreases in water diffusion parallel to the white
      matter fibers or axial diffusivity were observed in the SOD1 mice, which can be
      attributed to the axonal degeneration observed by electron microscopy. At the
      same time, radial diffusivity perpendicular to the spinal column increased in the
      SOD1 mice, reflecting reduced myelination. These results demonstrate the
      usefulness of MRI in tracking disease progression in live animals and will aid in
      the assessment of treatment efficacy. This method could also potentially be
      adapted to aid the diagnosis and assessment of ALS progression in humans.

PMID- 21185945
TI  - Analysis of thioredoxin peroxidase as a promising antigen for diagnosis of
      Fasciola gigantica infection: a preliminary study.
AB  - Buffalo fasciolosis induced by Fasciola gigantica causes important economic
      losses in tropical areas of Asia. Detection of prepatent infection is essential
      to control this disease. Classical tools such as coprology, necroscopy or ELISA
      based on crude extracts from F. gigantica are poorly sensitive or specific.
      Purified antigens could be used to increase these parameters. Western blot
      analysis and mass spectrometry of a fraction of F. gigantica excretory-secretory
      products obtained by gel filtration showed that thioredoxin peroxidase could be a
      potential antigen for serodiagnosis: it was recognized from the 2nd week after
      infection, by all buffalo experimentally or naturally infected with F. gigantica
      but not by healthy animals.

PMID- 21185944
TI  - Activation of human macrophages by bacterial components relieves the restriction
      on replication of an interferon-inducing parainfluenza virus 5 (PIV5) P/V mutant.
AB  - Macrophages regulate immune responses during many viral infections, and can be a
      major determinant of pathogenesis, virus replication and immune response to
      infection. Here, we have addressed the question of the outcome of infection of
      primary human macrophages with parainfluenza virus 5 (PIV5) and a PIV5 mutant
      (P/V-CPI-) that is unable to counteract interferon (IFN) responses. In cultures
      of naive monocyte-derived macrophages (MDMs), WT PIV5 established a highly
      productive infection, whereas the P/V-CPI- mutant was restricted for replication
      in MDMs by IFN-beta. Restricted replication in vitro was relieved in MDM that had
      been activated by prior exposure to heat killed Gram positive bacteria, including
      Listeria monocytogenes, Streptococcus pyogenes, and Bacillus anthracis. Enhanced
      replication of the P/V mutant in MDM previously activated by bacterial components
      correlated with a reduced ability to produce IFN-beta in response to virus
      infection, whereas IFN signaling was intact. Activated MDM were found to
      upregulate the synthesis of IRAK-M, which has been previously shown to negatively
      regulate factors involved in TLR signaling and IFN-beta production. We discuss
      these results in terms of the implications for mixed bacteria-virus infections
      and for the use of live RNA virus vectors that have been engineered to be
      attenuated for IFN sensitivity.

PMID- 21185946
TI  - Comparison of microglomerular structures in the mushroom body calyx of neopteran
      insects.
AB  - Mushroom bodies (MBs) are prominent neuropils in the insect brain involved in
      higher order processing such as sensory integration, learning and memory, and
      spatial orientation. The size and general morphology of MBs are diverse across
      insects. In this study we comparatively investigated the microstructure of
      synaptic complexes (microglomeruli) in major sensory input regions of the MBs,
      the calyces, across various neopteran insect species. Pre- and postsynaptic
      compartments of microglomeruli were analyzed using anti-synapsin
      immunocytochemistry, f-actin-phalloidin labeling and high-resolution confocal
      microscopy. Our results suggest that calycal microglomeruli are present across
      all investigated neopteran insect species, but differences are found in the
      distribution of synapsin and f-actin within their pre- and postsynaptic
      compartments. Hymenopteran MBs contain the highest number and packing density of
      microglomeruli compared to all other species from the different insect orders we
      investigated. We conclude that the evolution of high numbers of microglomeruli in
      Hymenoptera may reflect an increase in synaptic microcircuits, which could
      enhance the computational capacities of the MBs.

PMID- 21185949
TI  - To the editor: Differentiating orthodromic reciprocating tachycardia from
      atrioventricular nodal reentrant tachycardia.

PMID- 21185950
TI  - Real-time electrogram analysis for monitoring coronary blood flow during human
      ventricular fibrillation: implications for CPR.
AB  - BACKGROUND: Effective chest compressions during prolonged ventricular
      fibrillation (VF) have been shown to increase the chances of successful
      defibrillation to a rhythm associated with a sustainable cardiac output. There is
      currently no effective method of recording the degree of antegrade coronary
      artery flow during chest compression in VF. OBJECTIVE: This study sought to
      quantify the relationship between the antegrade coronary flow and the
      characteristics of human VF using near real-time wavelet-based
      electrocardiographic markers. METHODS: VF experiments were conducted in 8
      isolated human hearts. The Langendorff perfusion enabled different flow rates
      (perfusion) during VF, which allowed for the simulation of chest compression with
      different efficacies. After the initiation of VF, the hearts were maintained in
      ischemia (no flow) for 3 minutes, followed by a 2-minute reperfusion and
      defibrillation. The experiments were repeated at flows of 0%, 30%, and 100% of
      baseline perfusion, and volume-conducted surface electrograms were recorded and
      analyzed using continuous wavelet transform in 5-second frames. RESULTS: Near
      real-time wavelet features were derived that demonstrated significant differences
      in the multicomponent nature of VF signals and predicted perfusion rate
      characteristics for different flow rates (i.e., 0%, 30%, and 100%; P < .0006). A
      pattern classifier was trained using the feature values from 5 hearts, and the
      flow rates for 3 additional hearts were predicted with an accuracy of 90%.
      CONCLUSION: VF electrogram characteristics as measured by wavelet analysis relate
      to antegrade coronary flow rate during VF. These findings suggest that chest
      compression efficacy of physiological importance could be monitored using near
      real-time wavelet analysis.

PMID- 21185951
TI  - Atrial flutter: right, left, or both?

PMID- 21185952
TI  - Amphioxus Tbx6/16 and Tbx20 embryonic expression patterns reveal ancestral
      functions in chordates.
AB  - T-box transcription factors are found in all metazoans and play diverse roles
      during embryogenesis. In the cephalochordate amphioxus, nine T-box genes were
      previously identified. In this work we undertook the analysis of the embryonic
      expression pattern of Tbx6/16 and Tbx20, the last two T-box genes for which no
      such data are available. We found that Tbx6/16 is expressed in the unsegmented
      paraxial mesoderm, in a subpopulation of neurons, and in the tail epidermis.
      Comparison with the expression patterns of the different vertebrate orthologues
      indicates a conserved role of those genes in posterior mesoderm formation in
      chordates. Tbx20 expression is detected in the ventral mesoderm of amphioxus
      embryos, in cells that are proposed to be precursors of the amphioxus myocardium,
      in some neurons of the neural tube, and in the pre-oral pit which is thought to
      be the homologue of the vertebrate adenohypophysis. In vertebrates, Tbx20 is also
      one of the first genes expressed in the embryonic heart field, suggesting that
      the function of this gene in heart development has been conserved during chordate
      evolution.

PMID- 21185953
TI  - Injectable calcium phosphate cement with PLGA, gelatin and PTMC microspheres in a
      rabbit femoral defect.
AB  - In this study, we investigated the in vivo degradation properties and tissue
      response towards injectable calcium phosphate cement (CPC) with no further
      addition, or calcium phosphate composite cement containing approximately 50 vol.%
      of microspheres. Three types of spheres were assessed, i.e. poly(lactic-co
      glycolic acid) (PLGA), gelatin (GEL) and poly(trimethylene carbonate) (PTMC). The
      cements were injected into 4.6 mm diameter and 6mm deep cylindrical defects in
      the femoral condyle of New Zealand white rabbits, hardened in situ and, after
      wound closure, left to heal for 4, 8 and 12 weeks (n=6 for each composition and
      time period). After retrieval, specimens were analyzed using histological and
      histomorphometrical methods. Results showed that non-modified CPCs showed
      excellent bone contact but only very limited erosion at the surface. The CPC/PLGA
      implant degraded almost completely, while tissue response significantly improved
      at each time period. CPC/PTMC showed slower degradation characteristics compared
      to CPC/PLGA. Finally, at all time periods, there was an evident inflammatory
      response to the CPC/GEL composite cement. In conclusion, the degradation
      properties of the CPC/PLGA microspheres composite and its bone response when
      implanted into the femoral condyles of rabbits were significantly better than
      those of CPC/gelatin and CPC/PTMC microspheres composites.

PMID- 21185954
TI  - A comparative study of mesoporous glass/silk and non-mesoporous glass/silk
      scaffolds: physiochemistry and in vivo osteogenesis.
AB  - Mesoporous bioactive glass (MBG) is a new class of biomaterials with a well
      ordered nanochannel structure, whose in vitro bioactivity is far superior than
      that of non-mesoporous bioactive glass (BG); the material's in vivo osteogenic
      properties are, however, yet to be assessed. Porous silk scaffolds have been used
      for bone tissue engineering, but this material's osteoconductivity is far from
      optimal. The aims of this study were to incorporate MBG into silk scaffolds in
      order to improve their osteoconductivity and then to compare the effect of MBG
      and BG on the in vivo osteogenesis of silk scaffolds. MBG/silk and BG/silk
      scaffolds with a highly porous structure were prepared by a freeze-drying method.
      The mechanical strength, in vitro apatite mineralization, silicon ion release and
      pH stability of the composite scaffolds were assessed. The scaffolds were
      implanted into calvarial defects in SCID mice and the degree of in vivo
      osteogenesis was evaluated by microcomputed tomography (MUCT), hematoxylin and
      eosin (H&E) and immunohistochemistry (type I collagen) analyses. The results
      showed that MBG/silk scaffolds have better physiochemical properties (mechanical
      strength, in vitro apatite mineralization, Si ion release and pH stability)
      compared to BG/silk scaffolds. MBG and BG both improved the in vivo osteogenesis
      of silk scaffolds. MUCT and H&E analyses showed that MBG/silk scaffolds induced a
      slightly higher rate of new bone formation in the defects than did BG/silk
      scaffolds and immunohistochemical analysis showed greater synthesis of type I
      collagen in MBG/silk scaffolds compared to BG/silk scaffolds.

PMID- 21185955
TI  - Bioactive SrO-SiO2 glass with well-ordered mesopores: characterization,
      physiochemistry and biological properties.
AB  - For a biomaterial to be considered suitable for bone repair it should ideally be
      both bioactive and have a capacity for controllable drug delivery; as such,
      mesoporous SiO(2) glass has been proposed as a new class of bone regeneration
      material by virtue of its high drug-loading ability and generally good
      biocompatibility. It does, however, have less than optimum bioactivity and
      controllable drug delivery properties. In this study, we incorporated strontium
      (Sr) into mesoporous SiO(2) in an effort to develop a bioactive mesoporous SrO
      SiO(2) (Sr-Si) glass with the capacity to deliver Sr(2+) ions, as well as a drug,
      at a controlled rate, thereby producing a material better suited for bone repair.
      The effects of Sr(2+) on the structure, physiochemistry, drug delivery and
      biological properties of mesoporous Sr-Si glass were investigated. The prepared
      mesoporous Sr-Si glass was found to have an excellent release profile of
      bioactive Sr(2+) ions and dexamethasone, and the incorporation of Sr(2+) improved
      structural properties, such as mesopore size, pore volume and specific surface
      area, as well as rate of dissolution and protein adsorption. The mesoporous Sr-Si
      glass had no cytotoxic effects and its release of Sr(2+) and SiO(4)(4-) ions
      enhanced alkaline phosphatase activity - a marker of osteogenic cell
      differentiation - in human bone mesenchymal stem cells. Mesoporous Sr-Si glasses
      can be prepared to porous scaffolds which show a more sustained drug release.
      This study suggests that incorporating Sr(2+) into mesoporous SiO(2) glass
      produces a material with a more optimal drug delivery profile coupled with
      improved bioactivity, making it an excellent material for bone repair
      applications.

PMID- 21185956
TI  - Midkine-deficiency increases the anabolic response of cortical bone to mechanical
      loading.
AB  - The adaptive response of bone to load is dependent on molecular factors,
      including growth factor signaling, which is involved in the regulation of
      proliferation, differentiation and function of osteoblasts and osteoclasts. Based
      on a recent study, which has shown that the deficiency of growth factor midkine
      (Mdk) in mice at 12 and 18 months of age resulted in increased trabecular bone
      formation, we hypothesized that mechanically-induced bone remodeling may, at
      least in part, be dependent on Mdk expression. To investigate this, we loaded the
      ulnae of Mdk-deficient mice and appropriate wild-type mice at the age of 12
      months using the in vivo ulna loading model. Histomorphometric quantification of
      the periosteal bone demonstrated an increased mineralizing surface, mineral
      apposition rate, and bone formation rate in ulnae of Mdk-deficient mice compared
      to wild-type mice in response to loading. Because Mdk has been shown to bind to a
      complex of receptor-type protein tyrosine phosphatase zeta (Ptprz) and low
      density lipoprotein receptor-related protein-6 (Lrp-6) together with the
      alpha4beta1- and alpha6beta1-integrins, we performed in vitro studies using
      osteoblastic cells, transiently over-expressing Mdk, Wnt-3a, and Ptprz to
      evaluate whether Mdk has a role in regulating bone formation by modulating Wnt
      signaling. We observed a negative effect of Mdk on Wnt signaling, the extent of
      which appeared to be dependent on Ptprz expression. Moreover, we performed in
      vitro loading studies with osteoblasts treated with recombinant Mdk and observed
      a negative effect on the expression of Wnt target genes, which play a critical
      role in osteoblast proliferation. In summary, our data demonstrate that Mdk
      deficiency in mice has an anabolic effect on mechanically induced cortical bone
      formation. This could be due to an improved osteoblast function based on an
      enhancement of beta-catenin-dependent Wnt signaling by both Mdk-deficiency and
      mechanical loading.

PMID- 21185957
TI  - Ring in the new ....

PMID- 21185958
TI  - Serving the public: health literacy and food deserts.

PMID- 21185959
TI  - Support for the US Guidelines for the Diagnosis and Management of Food Allergy.

PMID- 21185960
TI  - Guidelines for the Diagnosis and Management of Food Allergy in the United States:
      summary of the NIAID-sponsored expert panel report.

PMID- 21185961
TI  - Translating the Dietary Guidelines for Americans 2010 to bring about real
      behavior change.

PMID- 21185962
TI  - What does the Journal's impact factor mean to you?

PMID- 21185963
TI  - To boldly go where no food has gone before.

PMID- 21185964
TI  - The impact of pregnancy nutrition on offspring obesity.

PMID- 21185965
TI  - A quality-adjusted life year of prevention: the cost-effectiveness of nutrition
      counseling.

PMID- 21185966
TI  - Cost-effectiveness analysis of a low-fat diet in the prevention of breast and
      ovarian cancer.
AB  - BACKGROUND: Results of the Women's Health Initiative Randomized Controlled
      Dietary Modification Trial (WHI-DM) suggest that a low-fat diet may be associated
      with beneficial health outcomes for specific groups of women. OBJECTIVE: The
      objective is to assess how cost-effective the WHI-DM would be if implemented as a
      public health intervention and under the sponsorship of private health insurers
      and Medicare. Breast and ovarian cancers are the health outcomes of interest.
      PARTICIPANTS: Two groups of WHI-DM participants form the target population for
      this analysis: participants consuming >36.8% of energy from fat at baseline, and
      participants at high risk for breast cancer with 32% or more of energy from fat
      at baseline. METHODS: This study uses Markov cohort modeling, following societal
      and health care payer perspectives, with Monte Carlo simulations and one-way
      sensitivity analyses. WHI-DM records, nationally representative prices, and
      published estimates of medical care costs were the sources of cost information.
      Simulations were performed for hypothetical cohorts of women aged 50, 55, 60, 65,
      or 70 years at the beginning of the intervention. Effectiveness was estimated by
      quality-adjusted life years (QALYs) and the main outcome measure was the
      incremental cost-effectiveness ratio (ICER). RESULTS: Following the societal
      perspective, the ICERs for the 50-year old cohort are $13,773/QALY (95%
      confidence interval $7,482 to $20,916) for women consuming >36.8% of energy from
      fat at baseline and $10,544/QALY ($2,096 to $23,673) for women at high risk for
      breast cancer. The comparable ICER from a private health care payer perspective
      is $66,059/QALY ($30,155 to $121,087) and from a Medicare perspective, it is
      $15,051/QALY ($6,565 to $25,105). CONCLUSIONS: The WHI-DM is a cost-effective
      strategy for the prevention of breast and ovarian cancers in the target
      population, from both societal and Medicare perspectives. Private health care
      payers have a relative short timeframe to realize a return on investment, since
      after age 65 years the financial benefits associated with the prevention program
      would accrue to Medicare. For this reason, the intervention is not cost-effective
      from a private health care payer perspective.

PMID- 21185968
TI  - A computer support program that helps clinicians provide patients with metabolic
      syndrome tailored counseling to promote weight loss.
AB  - BACKGROUND: Physician counseling can help patients make substantial changes in
      diet and physical activity behaviors that can result in weight loss and a
      reduction in metabolic risk factors. Unfortunately, time constraints and a lack
      of training often make it difficult for physicians to provide effective
      counseling. The objective in this study was to test the effect of a computerized
      support tool to enhance brief physician-delivered health lifestyle counseling to
      patients with increased metabolic risk factors during two usual care visits.
      DESIGN/SETTING/PARTICIPANTS: This is a prospective controlled trial of a 12-month
      intervention conducted at two large community health centers serving mostly
      Hispanic patients. Participants (n = 279) had a body mass index (calculated as
      kg/m2) >= 25 and at least two components of the metabolic syndrome. INTERVENTION:
      In the intervention group, a computer program was used to help patients set
      tailored self-management goals for weight loss, nutrition, and physical activity.
      Goals were then reviewed and reinforced at clinic visits with participants'
      physicians at baseline and again at 6 months. The control group received care as
      usual. Data were collected between July 2007 and August 2008. MAIN OUTCOME
      MEASURES: Change in body weight was the primary outcome. Secondary measures
      included changes in blood glucose, blood cholesterol, blood pressure, physical
      activity, and energy intake. RESULTS: Significantly more patients in the
      intervention group lost >= 5% of their body weight at 12 months than controls
      (26.3% vs 8.5%; odds ratio = 3.86; P < 0.01). Loss of > 5% of total body weight
      was associated with improvements in cardiovascular risk factors, including low
      density lipoprotein cholesterol (-14.0 vs -4.1 mg/dL; P = 0.04). CONCLUSIONS: A
      brief computer-based intervention designed to increase the dialogue between
      patients and clinicians about behavioral goals can lead to increased 12-month
      weight loss.

PMID- 21185967
TI  - Comparison of dietary intake of overweight postpartum mothers practicing
      breastfeeding or formula feeding.
AB  - BACKGROUND: Weight gain in the postpartum period is a risk factor for long-term
      obesity. Investigations of dietary intake among lactating and nonlactating
      overweight women might identify nutritional concerns specific to this population.
      OBJECTIVE: To compare nutrient, meal, and snack intakes, food-group servings and
      prevalence of dieting among fully breastfeeding (BF), mixed breast and formula
      feeding (MF), and formula feeding (FF) overweight and obese women. The second aim
      was to compare nutrient intakes and food-group servings to the Dietary Reference
      Intake and MyPyramid recommendations, respectively. DESIGN: Data were collected
      from September 2004 through April 2006 in Durham, NC. Infant feeding practices
      and dietary information were collected on 450 women between 6 and 9 weeks
      postpartum. Two 24-hour dietary recalls were completed by phone, using Nutrition
      Data Systems for Research. Analysis of covariance was used to compare infant
      feeding groups in dietary quality (nutrient intake per 1,000 kcal) and food-group
      servings, controlling for prepregnancy body mass index, race, age, education,
      income, and marital status. chi2 analysis was performed to determine differences
      in meal and snack intake and dieting among infant feeding groups. RESULTS: BF
      women consumed more energy (2,107 +/- 50 kcal) than MF (1,866 +/- 56 kcal) or FF
      (1,657 +/- 50 kcal) women (P < 0.001). Adjusted nutrient intake did not differ
      between groups. All groups were at risk for inadequate intakes of vitamins A, E,
      C, and folate and did not meet recommended servings of all food groups. BF women
      consumed lunch and snacks more frequently, were less likely to diet, and reported
      higher intakes of grains and desserts than MF and FF women. CONCLUSIONS: To help
      increase intakes of nutrients lacking in the diet and prevent postpartum weight
      gain, overweight women should be encouraged to increase fruits, vegetables, low
      fat dairy, whole grains, legumes, and healthy types of fat, while decreasing
      refined grains, regular soda, sweetened beverages, and desserts.

PMID- 21185969
TI  - Dietary patterns and survival of older adults.
AB  - BACKGROUND: Recent research has linked overall dietary patterns to survival in
      older adults. OBJECTIVES: The objective of this study was to determine the
      dietary patterns of a cohort of older adults, and to explore associations of
      these dietary patterns with survival over a 10-year period. A secondary goal was
      to evaluate participants' quality of life and nutritional status according to
      their dietary patterns. DESIGN: The Health, Aging, and Body Composition Study is
      a prospective cohort study of 3,075 older adults. In this study, all-cause
      mortality was assessed from baseline through Year 10. Food intake was estimated
      with a modified Block food frequency questionnaire, and dietary patterns of 2,582
      participants with complete data were derived by cluster analysis. RESULTS: Six
      dietary pattern clusters were identified, including a Healthy Foods cluster,
      characterized by higher intake of low-fat dairy products, fruit, whole grains,
      poultry, fish, and vegetables. Both the High-Fat Dairy Products and Sweets and
      Desserts clusters had a 1.4-fold higher risk of mortality than the Healthy Foods
      cluster after adjusting for potential confounders. The Healthy Foods cluster also
      had significantly more years of healthy life and more favorable levels of
      selected nutritional biomarkers than the other clusters. CONCLUSIONS: A dietary
      pattern consistent with current guidelines to consume relatively high amounts of
      vegetables, fruit, whole grains, poultry, fish, and low-fat dairy products may be
      associated with superior nutritional status, quality of life and survival in
      older adults.

PMID- 21185971
TI  - Publishing nutrition research: a review of multivariate techniques--part 1.
AB  - This article is the seventh in a series reviewing the importance of research
      design, analyses, and epidemiology in the conduct, interpretation, and
      publication of nutrition research. Although there are a variety of factors to
      consider before conducting nutrition research, the techniques used to conduct the
      statistical analysis are fundamental for translating raw data into interpretable
      findings. The statistical approach must be considered during the design phase of
      any study and often involves the use of multivariate analytical techniques.
      Multivariate analytical techniques represent a variety of mathematical models
      used to measure and quantify an exposure-disease or an exposure-outcome
      association, taking into account important factors that can influence this
      relationship. The primary purpose of this review is to introduce the more
      commonly used multivariate techniques, including linear and logistic regression
      (simple and multiple), and survival analyses (Kaplan Meier plots and Cox
      regression). These techniques are described in detail, providing basic
      definitions and practical examples with nutrition relevancy. An appreciation for
      the general principles within and presented previously in this article series is
      vital for enhancing the rigor in which nutrition-related research is implemented,
      reviewed, and published.

PMID- 21185970
TI  - Self-monitoring in weight loss: a systematic review of the literature.
AB  - Self-monitoring is the centerpiece of behavioral weight loss intervention
      programs. This article presents a systematic review of the literature on three
      components of self-monitoring in behavioral weight loss studies: diet, exercise,
      and self-weighing. This review included articles that were published between 1993
      and 2009 that reported on the relationship between weight loss and these self
      monitoring strategies. Of the 22 studies identified, 15 focused on dietary self
      monitoring, one on self-monitoring exercise, and six on self-weighing. A wide
      array of methods was used to perform self-monitoring; the paper diary was used
      most often. Adherence to self-monitoring was reported most frequently as the
      number of diaries completed or the frequency of log-ins or reported weights. The
      use of technology, which included the Internet, personal digital assistants, and
      electronic digital scales were reported in five studies. Descriptive designs were
      used in the earlier studies whereas more recent reports involved prospective
      studies and randomized trials that examined the effect of self-monitoring on
      weight loss. A significant association between self-monitoring and weight loss
      was consistently found; however, the level of evidence was weak because of
      methodologic limitations. The most significant limitations of the reviewed
      studies were the homogenous samples and reliance on self-report. In all but two
      studies, the samples were predominantly white and women. This review highlights
      the need for studies in more diverse populations, for objective measures of
      adherence to self-monitoring, and for studies that establish the required dose of
      self-monitoring for successful outcomes.

PMID- 21185972
TI  - Association of modifiable and nonmodifiable factors with vitamin D status in
      pregnant women and neonates in Oakland, CA.
AB  - There is little information on the contribution of modifiable vs nonmodifiable
      factors to maternal and neonatal vitamin D status in temperate regions of the
      United States. The purpose of this cross-sectional observation study conducted
      between December 2006 and February 2008 was to identify associations between
      observed and measured maternal characteristics and vitamin D status at term in
      pregnant women and their infants in a multiethnic community in Oakland, CA. Two
      hundred seventy-five pregnant women aged 18 to 45 years and carrying a singleton
      fetus were recruited and data from 210 mother-infant pairs were included in
      analyses. Analysis of covariance identified predictors of maternal and cord serum
      25-hydroxyvitamin D [25(OH)D] in a multivariate model considering vitamin D
      intake, lifestyle factors, and skin pigmentation. Maternal serum 25(OH)D was
      significantly associated with season of delivery (P=0.0002), average daily D
      intake (P=0.0008), right upper inner arm pigmentation (P=0.0035), and maternal
      pre- or early-pregnancy body mass index (calculated as kg/m2) (P=0.0207). The
      same factors were significant for cord serum 25(OH)D, which was highly correlated
      with maternal serum 25(OH)D (r=0.79; P<0.0001). During the year, 54% of mothers
      and 90% of neonates had 25(OH)D <30 ng/mL (<75 nmol/L). Of women taking daily
      prenatal vitamin/mineral supplements (400 IU vitamin D), 50.7% had serum 25(OH)D
      <30 ng/mL (<75 nmol/L). In conclusion, 25(OH)D <30 ng/mL (<75 nmol/L) was
      prevalent in mothers and neonates across racial groups and seasons, and vitamin D
      status was associated with both modifiable and nonmodifiable risk factors.

PMID- 21185973
TI  - Validation of a food frequency questionnaire to assess intake of n-3
      polyunsaturated fatty acids in subjects with and without major depressive
      disorder.
AB  - The role of n-3 polyunsaturated fatty acids (PUFAs) in psychiatric illness is a
      topic of public health importance. This report describes development and
      biomarker validation of a 21-item, self-report food frequency questionnaire (FFQ)
      intended for use in psychiatric research to assess intake of alpha-linolenic acid
      (18:3n-3 [ALA]), docosahexaenoic acid (22:6n-3 [DHA]), and eicosapentaenoic acid
      (20:5n-3 [EPA]). In a cross-sectional study conducted from September 2006 to
      September 2008, sixty-one ethnically diverse adult participants with (n=34) and
      without (n=27) major depressive disorder completed this n-3 PUFA FFQ and provided
      a plasma sample. Plasma levels of n-3 PUFAs EPA and DHA, and n-6 PUFA arachidonic
      acid (20:4n-6 [AA]) were quantified by gas chromatography. Using Spearman's rho,
      FFQ-estimated intake correlated with plasma levels of DHA (r=0.50; P<0.0001) and
      EPA (r=0.38; P=0.002), but not with ALA levels (r=0.22; P=0.086). Participants
      were classified into quartiles by FFQ-estimated intake and plasma PUFA
      concentrations. Efficacy of the FFQ to rank individuals into same or adjacent
      plasma quartiles was 83% for DHA, 78.1% for EPA, and 70.6% for ALA;
      misclassification into extreme quartiles was 4.9% for DHA, 6.5% for EPA, and 8.2%
      for ALA. FFQ-estimated EPA intake and plasma EPA were superior to plasma AA
      levels as predictors of the plasma AA to EPA ratio. This brief FFQ can provide
      researchers and clinicians with valuable information concerning dietary intake of
      DHA and EPA.

PMID- 21185974
TI  - Postpartum teens' breakfast consumption is associated with snack and beverage
      intake and body mass index.
AB  - Addressing high-risk dietary patterns among postpartum teens may help reduce
      weight retention and prevent intergenerational obesity. The objective of this
      study was to describe the relationship between breakfast consumption and outcomes
      of snack and beverage intake and body mass index (BMI) among postpartum teens.
      During 2007-2009, 1,330 postpartum teens across 27 states participated in a cross
      sectional, baseline assessment of a group-randomized, nested cohort study.
      Participants were enrolled in the Parents as Teachers Teen Program and completed
      a 7-day recall of breakfast, snack, and beverage consumption. BMI was calculated
      from heights and weights obtained by on-site staff. Sample descriptives were
      compared across breakfast consumption frequency groupings by one-way analysis of
      variance tests or chi2 tests. General linear models assessed relationships
      between breakfast consumption and measures of snack and sweetened beverage
      intake, water consumption, and BMI-for-age percentile. Almost half (42%) of the
      sample consumed breakfast fewer than 2 days per week. Those who ate breakfast 6
      to 7 days/week consumed 1,197 fewer kilocalories per week from sweet and salty
      snacks, 1,337 fewer kilocalories per week from sweetened drinks, and had a lower
      BMI compared to those who ate breakfast fewer than 2 days per week (P < 0.05).
      Consumption of fruit, vegetables, milk, water, and cereal as a snack were higher
      among regular breakfast consumers (P < 0.05). Although breakfast consumption
      among postpartum teens is low, those who regularly consume breakfast had
      healthier snacking behaviors and weight. Interventions are needed to encourage
      breakfast consumption among teen mothers.

PMID- 21185975
TI  - Influence of placement of a nutrition logo on cafeteria menu items on lunchtime
      food Choices at Dutch work sites.
AB  - This study investigated the effectiveness of labeling foods with the Choices
      nutrition logo on influencing cafeteria menu selection and the behavioral
      determinants of menu choices in work site cafeterias in the Netherlands. A
      cluster randomized controlled trial was conducted. Intervention cafeterias
      (n=13), where the Choices logo was used to promote healthier eating for a 3-week
      period, were compared with control cafeterias (n=12), which offered the same menu
      without the logo. Sales data were collected daily for 9 weeks, from March to May
      2009. In addition, employees from one intervention and one control company
      completed an online questionnaire at baseline and after the intervention (n=368)
      in which the behavioral determinants of food choice (ie, attitude, self-efficacy,
      and intention) and logo use were measured. Generalized estimating equation
      analyses, chi2 tests, t tests and linear regression analyses were performed. No
      nutritionally meaningful intervention effects were found in the sales of
      sandwiches, soups, snacks, fruit, and salads. Also, no significant differences in
      behavioral determinants were found. "Intention to eat healthier" and "paying
      attention to product information" were positively associated with self-reported
      consumption of foods with the Choices logo at lunch. The intervention did not
      have a significant effect on employees' lunchtime food choices. Labeling healthy
      choices might be useful for health-conscious employees in the volitional phase of
      behavior change. Further research should focus on the possible health benefits of
      menu reformulation in the catering sector.

PMID- 21185976
TI  - Frequency of soup intake is inversely associated with body mass index, waist
      circumference, and waist-to-hip ratio, but not with other metabolic risk factors
      in Japanese men.
AB  - Several previous studies have shown that the intake of soup negatively correlates
      with the body mass index (BMI), serum cholesterol and triacylglycerol levels, and
      blood pressure, suggesting that soup intake reduces metabolic risk. However, the
      correlation between soup intake and various metabolic risk factors has not been
      well-established. Especially, it has not been investigated in Asian countries.
      The aim of this study was to investigate the association of the frequency of soup
      intake and metabolic risk factors such as BMI, waist circumference, waist-to-hip
      ratio, serum cholesterol, serum triacylglycerol, blood glucose, and glycated
      hemoglobin. A cross-sectional study of 103 Japanese men aged 24 to 75 years was
      conducted. The intake of soup and other food was investigated by semi
      quantitative food frequency questionnaires. The correlation between the frequency
      of soup intake and metabolic risk factors was analyzed by multiple regression
      analysis with a linear model. The median value of frequency of soup intake was
      7.0 times per week. After adjusting for confounding factors such as age, energy
      intake, energy from alcohol intake, current smoking, and estimated energy
      expenditure, the frequency of soup intake was found to have a significant inverse
      association with BMI (P=0.040), waist circumference (P=0.024), and waist-to-hip
      ratio (P=0.001). However, no significant associations with other metabolic risk
      factors were found. Frequency of soup intake is negatively correlated with
      obesity-related physical parameters in Japanese men.

PMID- 21185977
TI  - Impact of a nutrition education program to increase intake of calcium-rich foods
      by Chinese-American women.
AB  - Chinese-American women have a high risk of osteoporosis. However, their calcium
      intake has been reported previously as considerably below the Dietary Reference
      Intake. Increasing consumption of calcium-rich foods, many of which are also
      fortified with vitamin D, is a safe way to increase their calcium and vitamin D
      intake. This study's objective was to pilot-test an intervention to help Chinese
      American women incorporate calcium-rich foods into their diet. This intervention
      was evaluated using a quasi-experimental study with a nested design and pre-,
      immediate post-, and 3-month follow-up assessments. Calcium and vitamin D intake,
      Theory of Planned Behavior constructs, and knowledge were measured at three time
      points. First-generation Chinese-American mothers between 35 and 55 years old
      (n=141) were recruited from six weekend Chinese schools. Three Chinese schools
      each were randomly assigned to the experimental (n=71) or control group (n=70).
      The experimental group received a free heel scan and six weekly interactive
      lessons designed based on the Theory of Planned Behavior. The control group
      received six weekly nonrelated financial lessons by mail. Changes for each
      measure were assessed by linear mixed model with repeated measures adjusted for
      confounding variables. Compared to the control group, the experimental group
      improved all measures considerably, except two subjective norm constructs
      (normative belief and motivation to comply) at post-assessments. The experimental
      group significantly increased its baseline calcium (t=7.898, P<0.001) and vitamin
      D intake (t=6.609; P<0.001) at posttest and this increase was retained at follow
      up. Results suggest that this theory-based intervention is effective for
      increasing the dietary calcium and vitamin D intake of Chinese-American women.

PMID- 21185978
TI  - School and district wellness councils and availability of low-nutrient, energy
      dense vending fare in Minnesota middle and high schools.
AB  - The Child Nutrition and WIC Reauthorization Act of 2004 required school districts
      participating in the federal school meals program to establish by the start of
      the 2006-2007 school year policies that included nutrition guidelines for all
      foods sold on school campus during the school day and policy development
      involving key stakeholders. For many schools, policy development was done by
      wellness councils. This study examined the association between having a wellness
      council and availability of low-nutrient, energy-dense foods/beverages in school
      vending machines following enactment of the federal legislation. In 2006-2007,
      Minnesota middle (n=35) and high (n=54) school principals reported whether their
      school and district had a wellness council. Trained research staff observed
      foods/beverages in vending machines accessible to students. Low-nutrient, energy
      dense foods/beverages (snacks >3 g fat or >200 calories/serving, and soda,
      fruit/sport drinks and reduced-fat/whole milk) were grouped into seven categories
      (eg, high-fat baked goods) and a food score was calculated. Higher scores
      indicated more low-nutrient, energy-dense vending fare. Multivariate linear
      regression, adjusted for school characteristics, was used to examine associations
      between scores and a three-category council variable (district-only; district and
      school; no council). Among schools, 53% had district-only councils, 38% district
      and school councils, and 9% had no council. Schools with both a district and
      school council had a significantly lower mean food score than schools without
      councils (P=0.03). The potential of wellness councils to impact availability of
      low-nutrient, energy-dense vending fare is promising. There may be an added
      benefit to having both a school and district council.

PMID- 21185979
TI  - American Dietetic Association revised standards of practice and standards of
      professional performance for registered Dietitians (generalist, specialty, and
      advanced) in diabetes care.

PMID- 21185980
TI  - Setting fees-where do I start?

PMID- 21185981
TI  - [Hand eczema and occupational disorders].
AB  - Hand eczema (HE) is a frequent skin disease, combining endogenous and exogenous
      factors. Occupational -or work-related- hand eczema (OHE) is frequently a chronic
      and relapsing disease, due to irritant and allergenic contacts. Burden of disease
      is important, since OHE strikes quality of life of the patient, has significant
      social and economic impact, and may jeopardize his professional future. The
      management of OHE combines etiological assessment, efficient symptomatic
      treatment and adaptation of working conditions.

PMID- 21185982
TI  - [Alitretinoin in chronic hand eczema: summary of clinical trials].
AB  - After an open preliminary study, two double-blind placebo-controlled randomized
      studies have confirmed the value of per os alitretinoin in the management of
      severe chronic hand eczema (CHE). The first showed dose-dependent efficacy and a
      response defined as "clear" or "almost clear" by 53% of the patients receiving 10
      40 mg of alitretinoin per day for 12 weeks. In the second multicenter study (the
      Bach study), comparing the efficacy of a 12-week alitretinoin treatment (10 mg,
      30 mg) to placebo for CHE, a "clear or almost clear" result was observed in 17%
      (placebo group), 28% (group alitretinoin 10 mg), and 48% (group alitretinoin 30
      mg). The onset of action was also significantly shorter in the group treated with
      30 mg of alitretinoin compared to the group treated with 10 mg. In a study of
      randomized retreatment versus placebo, 80% of the patients who were initially
      responders to alitretinoin and whose CHE had relapsed found "clear" or "almost
      clear" with alitretinoin 30 mg administered for 12-24 weeks compared to 48% with
      alitretinoin 10 mg. In all the studies, clinical tolerance was comparable and
      satisfactory, with the most frequent negative side effects being headache,
      flushing, and mucocutaneous signs identical to those compared with other
      retinoids. An increase in cholesterol and/or triglycerides was the most frequent
      biological side effect. Central hypothyroidism, with no clinical expression, was
      observed more rarely. These studies confirm that alitretinoin treatment can be
      envisaged as second-line therapy in adults with CHE that does not respond to well
      observed treatment with class potent or very potent dermocorticoids.

PMID- 21185983
TI  - [In the (re) discovering of the hand].

PMID- 21185984
TI  - [Hand for the dermatologist].
AB  - Through its anatomical, topographical, and functional distinctiveness, more than
      all other parts of the body, the hand is the interface between humans and their
      environment. All types of stimulus produce cutaneous signs in the hands, notably
      cold, light, pressure, contact, etc. Exposure to light makes it the region where
      photodermatosis is expressed, but also a particular site for cutaneous
      carcinogenesis. The countless chemical substances that the hand encounters can
      create specific or particular diseases in this location (irritative dermitis,
      contact eczema, hyperkeratosis, atrophy, etc.). The hand is also the site of
      infectious dermatosis transmission (erysipeloid, orf, mycobacteriosis, etc.),
      sometimes exotic (chromomycosis, histoplasmosis), and the site of plant
      penetration (protothecosis or more commonly thorns and splinters). The complexity
      of its vascularization and its many bones, joints, and tendons explain why it is
      a preferred area for signs of systemic diseases (diverse forms of lupus,
      dermatomyositis, inflammatory rheumatism, etc.). The nail unit alone shows
      innumerable signs of exogenic diseases, but also reflects certain internal
      diseases localized here with often characteristic signs. Here more than anywhere
      else, dermatology opens out to all of medicine.

PMID- 21185985
TI  - [Retinoids: mechanisms of action].
AB  - Retinoids, vitamin A derivatives, are natural or synthetic molecules with
      pleiotropic effects, which regulate cell differentiation, proliferation and
      apoptosis. In target cell, the active natural metabolites retinoic acid (RA) and
      9-cis-retinoic acid are synthetized from retinol by a two-step process with
      intermediate metabolite retinaldehyde. In 1987, the identification of the nuclear
      retinoic acid receptors that belong to the superfamily of nuclear receptors led
      to a significant progress in the comprehension of the mechanism of action of
      retinoids. There are two families of Retinoid Nuclear Receptors (RNR), the RA
      receptors (RAR), which natural ligand is RA, and the Retinoid X Receptors (RXR),
      which natural ligand is 9-cis-retinoic acid. Among synthetic retinoids,
      isotretinoin, acitretin, tazarotene and adapalene are ligands of the RAR,
      bexarotene is the first rexinoid (ligand of the RXR), alitretinoin the first
      panagonist (RAR+ RXR). For each family, there are 3 isotypes (alpha, beta,
      gamma), and for each isotype several isoforms. Each NRR is composed of 6 regions
      (A-F). 3 regions are of importance: the A/B region has a ligand-independent
      transcriptional activation function, the C region harbors the DNA binding domain,
      the E region harbors the ligand binding domain. To regulate the expression of
      target genes, NRR have to dimerize. RXR are obligatory in dimers (heterodimers
      RAR-RXR, homodimers RXR-RXR). Dimers binds specific sequences of DNA, present in
      the promoters of target genes. When the ligand, natural or synthetic, bind to
      RNR, coactivators are recruited and transcription factors are activated. In
      target cell, retinoids not utilized are degradated in polar metabolites by
      enzymes of cytochrome P450.

PMID- 21185986
TI  - Lessons for women's health from the Massachusetts reform: affordability,
      transitions, and choice.
AB  - Three years into Massachusetts' health insurance reform, we are beginning to see
      what that experience portends for women nationally in the wake of legislation
      similar to the Massachusetts model. Although the Massachusetts reform has been
      successful in terms of reducing the number of uninsured men and women, interviews
      with Massachusetts women reveal significant problems that remain to be addressed.
      In this paper, we offer snapshots of three women whom we interviewed on the cusp
      of the Massachusetts reform. None of the women had insurance at the time; thus,
      health care reform represents a significant improvement in their access to care.
      However, as these snapshots indicate, major challenges remain in terms of
      affordability, continuity of coverage, and systemic complexities in choosing
      plans.

PMID- 21185987
TI  - Relevance of gender-sensitive policies and general health indicators to compare
      the status of South Asian women's health.
AB  - BACKGROUND: despite goals for gender equity in South Asia, the relationship
      between gender-sensitive policies and the empowerment of women is complex and
      requires an analysis of how policies align with a broad set of social, cultural,
      political, and economic indicators that relate to women's health. METHODS:
      through a review of four documents under the umbrella of the World Health
      Organization and the United Nations, a list of 17 gender-sensitive policy and 17
      general health indicators was generated with a focus on health, education,
      economic, and political empowerment and violence against women. A series of
      policy documents and international and national databases that are accessible in
      the public domain were the major tools used to find supporting documentation to
      address women's health outcomes in Bangladesh, India, Nepal, Pakistan, and Sri
      Lanka. RESULTS: all five South Asian countries had several gender-sensitive
      policies that were measurable by indicators that contribute to health.
      Examination of political and economic status, birth sex ratios, human
      trafficking, illiteracy rates, maternal mortality rates, contraception
      prevalence, fertility rates, knowledge of HIV/AIDS prevention, access to skilled
      birth attendants, and microfinance show that large gender inequities still
      prevail despite the presence of gender-sensitive policies. CONCLUSION: in many
      cases, the presence of gender-sensitive policies did not reflect the realization
      of gender equity over a wide range of indicators. Although the economic,
      political, social, and cultural climates of the five countries may differ, the
      integration of women's needs into the formulation, implementation, and monitoring
      of policies is a universal necessity to achieve positive outcomes.

PMID- 21185988
TI  - Balancing work and family after childbirth: a longitudinal analysis.
AB  - BACKGROUND: in the United States, women with young children have dramatically
      increased their participation in the workforce, resulting in greater potential
      conflict between work and family roles. However, few studies have examined
      postpartum work-family conflict. This study examined associations between work
      family conflict and women's health after childbirth. METHODS: employed women, 18
      years of age and older, were recruited while hospitalized for childbirth and
      followed for 18 months (n = 541; 66% response rate). Health outcomes were
      measured using the Short Form 12, version 2. Longitudinal fixed-effects models
      estimated the associations between work-family conflict (modeled as job and home
      spillover) and health. RESULTS: women who reported high levels of job spillover
      to home had mental health scores slightly, but significantly, worse than women
      who reported low levels of spillover (beta = -1.26; SE = 0.47). Women with medium
      and high levels of home spillover to job also reported worse mental health (beta
      = -0.81, SE = 0.30; and beta = -1.52, SE = 0.78) relative to those with low
      spillover. Women who reported medium (versus low) levels of home spillover
      reported slightly improved physical health (beta = 0.64, SE = 0.30). There was no
      significant association between job spillover and physical health. CONCLUSION:
      this study focused exclusively on employed postpartum women. Results illustrate
      that job and home spillover are associated with maternal mental and physical
      health. Findings also revealed that flexible work arrangements were associated
      with poorer postpartum mental health scores, which may reflect unintended
      consequences, such as increasing the amount of work brought home.

PMID- 21185989
TI  - Health status, health service use, and satisfaction according to sexual identity
      of young Australian women.
AB  - OBJECTIVES: we sought to compare physical and mental health status, health
      service use, and satisfaction among young Australian women of varying sexual
      identity; and to explore associations of all of these variables with satisfaction
      with their general practitioner (GP). METHODS: data are from the youngest cohort
      of women in the Australian Longitudinal Study on Women's Health surveyed in 2003.
      The sample included women aged 25 to 30 who identified as exclusively
      heterosexual (n = 8,083; 91.3%), mainly heterosexual (n = 568; 6.4%), bisexual (n
      = 100; 1.1%), or lesbian (n = 99; 1.1%). Univariate analyses compared self
      reported mental health, physical health, access to GP services, and satisfaction
      across the four sexual identity groups. Linear regression, controlling for
      education, income, and residence, was used to identify factors associated with GP
      satisfaction. RESULTS: sexual minority women (lesbian, bisexual, and mainly
      heterosexual) were significantly more likely than were heterosexual women to
      report poorer mental health and to have more frequently used health services;
      depression was strongly associated with mental health services use. Bisexual and
      mainly heterosexual women were most likely to report poorer general health,
      abnormal Pap tests, sexually transmissible infections, urinary tract infections,
      hepatitis B or C virus infection, and asthma. Lesbians were most likely to have
      never had a Pap test or be underscreened. All sexual minority women had lower
      continuity of GP care and lower satisfaction with that care than heterosexual
      women. CONCLUSION: underlying social determinants of physical and mental health
      disparities experienced by sexual minority women require exploration, including
      the possible effects of discrimination and marginalization on higher levels of
      risk taking. Lower continuity of care and lower satisfaction with GP services
      also need further investigation.

PMID- 21185990
TI  - A comparison of individual and social vulnerabilities, health, and quality of
      life among Canadian women with mental diagnoses and young children.
AB  - PURPOSE: this study examined whether differences exist among women with mental
      health issues who had either young, adult, or no children in relation to their
      individual and social vulnerabilities, health, and quality of life. METHODS: the
      design of this study was a secondary quantitative analysis of data extracted from
      a larger Canadian 5-year study focused on mental health and housing. This study's
      sample included 234 female psychiatric consumer/survivors: 108 (46%) women
      reported having no children, 68 (29%) had at least one child younger than 18
      years of age, and 58 (25%) had children 18 years of age or older. The women
      completed structured interviews between 2004 and 2006. FINDINGS: seventy-nine
      percent of mothers were separated from their young children. In comparison with
      women with older children and those without children, women with young children
      were more often homeless, had fewer strengths/resources, greater physical but
      lower cognitive/intellectual functioning, and a low perception of quality of life
      regarding their financial situation. In addition, women with young children
      reported the greatest problem with substance use and poorest quality of life
      regarding daily activities, health, and overall quality of life. These results,
      however, were mediated by the confounding effects of housing. No differences were
      identified between groups regarding utilization of health and social services.
      CONCLUSION: these findings support the need for early integrated health and
      social interventions that assist women achieve their well-being.

PMID- 21185991
TI  - Gender differences in life expectancy and disability-free life expectancy among
      older adults in Sao Paulo, Brazil.
AB  - BACKGROUND: research on life expectancy has demonstrated the negative impact of
      disability on the health of older adults and its differential effects on women as
      evidenced by their higher disabled life expectancy (DLE). The goal of the present
      study was to investigate gender differences in total life expectancy (TLE),
      disability-free life expectancy (DFLE), and DLE; examine gender differences on
      personal care assistance among older adults in Sao Paulo, Brazil; and discuss the
      implications for public policies. METHODS: the sample was drawn from two waves
      (2000, 2006) of the dataset of Salud, Bienestar, y Envejecimiento, a large
      longitudinal study conducted in Sao Paulo (n = 2,143). The study assessed
      disability using the activities of daily living (ADL). The interpolation of
      Markov Chain method was used to estimate gender differences in TLE, DLE, and
      DFLE. FINDINGS: TLE at age 60 years was approximately 5 years longer for women
      than men. Women aged 60 years were expected to live 28% of their remaining lives
      twice the percentage for men-with at least one ADL disability. These women also
      lived more years (M = 0.71, SE = 0.42) with three or more ADL disabilities than
      men (M = 0.82, SE = 0.16). In terms of personal care assistance, women received
      more years of assistance than men. CONCLUSION: among older adults in Sao Paulo,
      women lived longer lives but experienced a higher and more severe disability
      burden than men. In addition, although women received more years of personal
      assistance than men, women experienced more unmet care assistance needs.

PMID- 21185992
TI  - HPV vaccine promotion: does referring to both cervical cancer and genital warts
      affect intended and actual vaccination behavior?
AB  - BACKGROUND: young women have poor awareness that human papillomavirus (HPV) can
      cause both cervical cancer and genital warts, a sexually transmitted infection
      (STI). A newly developed HPV vaccine can provide protection against both cervical
      cancer and genital warts. This vaccine could be promoted by health
      authorities/professionals as preventing cervical cancer plus genital warts, or
      cervical cancer alone. Because stigma around STIs may reduce acceptance of the
      vaccine, the effect of information framing ('cervical cancer' versus 'cervical
      cancer plus genital warts') on intention to receive the HPV vaccine and actual
      uptake behavior was examined using the health belief model (HBM). METHODS: we
      randomized 159 young women under the age of 27 to receive one of two variations
      of a fact-sheet describing the HPV vaccine as 1) preventing cervical cancer or 2)
      preventing cervical cancer and genital warts. RESULTS: the results revealed low
      HPV knowledge (22%) and high HPV vaccination intention (79%), which was not
      influenced by information framing. Receipt of the vaccine at the 2-month follow
      up was 37%, and was also not influenced by information framing. The overall HBM
      predicted vaccination intention (p < .001) and behavior (p = .002). However, only
      barriers (p = .029) and benefits (p = .001) independently predicted HPV
      vaccination intention; susceptibility (p = .023) and benefits (p = .033)
      independently predicted HPV vaccination behavior. CONCLUSION: highlighting the
      sexual transmissibility of HPV does not seem to lower vaccination intentions or
      behaviors among young women. Potential challenges for promotion of the HPV
      vaccination program in Australia and worldwide are discussed.

PMID- 21185993
TI  - Menstrual suppression for combat operations: advantages of oral contraceptive
      pills.
AB  - BACKGROUND: increasing numbers of women are deployed to austere settings in which
      menstruation may impose logistical challenges. Minimal data exists about the use
      of oral contraceptive pills (OCPs) for menstrual suppression in this population.
      Post-deployment survey was undertaken to establish prevalence of continuous OCP
      use, perceived barriers, and associations with menstrual burden in a military
      population within the austere environment. METHODS: voluntary and anonymous 44
      item questionnaire. RESULTS: of 500 women, 78% (n = 390) had personal experience
      using OCPs and 66% (n = 330) desired menstrual suppression. However, only 40% (n
      = 192) reported any OCP use and only 21% (n = 99) reported continuous use during
      deployment. Sixty-seven percent of women reported some difficulty in daily pill
      compliance and nearly half (45%) missed >= 1 pill per week in the austere
      setting. Continuous users were nearly twice as compliant as conventional users (p
      = .019) and compliant OCP users reported significantly less menstrual burden than
      noncompliant users (p = .017). Almost all women (85%) desired mandatory education
      about menstrual suppression through OCPs. CONCLUSION: despite OCP experience and
      desire for amenorrhea, prevalence of extended cycle OCP use in this population is
      low. Extended OCPs users in the austere setting report improved compliance and
      reduced menstrual burden compared with conventional users. Education about OCPs
      is highly desirable for most military women and may benefit those in austere
      settings.

PMID- 21185995
TI  - The Suleman octuplet case and egregious ethical breaches.

PMID- 21185996
TI  - Congenital hyperinsulinism.

PMID- 21185994
TI  - The burden of illness in the first year home: do male and female VA users differ
      in health conditions and healthcare utilization.
AB  - BACKGROUND: we sought to describe gender differences in medical and mental health
      conditions and health care utilization among veterans who used Veterans Health
      Administration (VA) services in the first year after combat in Iraq and
      Afghanistan. METHODS: this is an observational study, using VA administrative and
      clinical data bases, of 163,812 Operation Enduring Freedom/Operation Iraqi
      Freedom veterans who had enrolled in VA and who had at least one visit within 1
      year of last deployment. RESULTS: female veterans were slightly younger (mean
      age, 30 years vs. 32 for men; p <.0001), twice as likely to be African American
      (30% vs. 15%; p <.0001), and less likely to be married (32% vs. 49%; p < .0001).
      Women had more visits to primary care (2.6 vs. 2.0; p < .001) and mental health
      (4.0 vs. 3.6; p < .001) clinics and higher use of community care outside the VA
      (14% vs. 10%; p < .001). After adjustment for significant demographic
      differences, women were more likely to have musculoskeletal and skin disorders,
      mild depression, major depression, and adjustment disorders, whereas men were
      more likely to have ear disorders and posttraumatic stress disorder. Thirteen
      percent of women sought care for gynecologic examination, 10% for contraceptive
      counseling, and 7% for menstrual disorders. CONCLUSION: female veterans had
      similar rates of physical conditions, but higher rates of some mental health
      disorders and additionally, used the VA for reproductive health needs. They also
      had slightly greater rates of health care service use. These findings highlight
      the complexity of female Veteran health care and support the development of
      enhanced comprehensive women's health services within the VA.

PMID- 21185997
TI  - Morphologic analysis of focal and diffuse forms of congenital hyperinsulinism.
AB  - Congenital hyperinsulinism is clinically characterized by an inappropriate
      insulin secretion resulting in recurrent severe hypoglycemia. Nesidioblastosis,
      the proliferation of islet cells budding off from ducts, has been considered for
      years as the histologic lesion responsible for the syndrome. In our morphologic
      studies, we demonstrate that nesidioblastosis is not specific of the disease,
      which is actually not a single entity. Indeed, we recognize the existence of 2
      different forms-a diffuse form and a focal form-and demonstrate that they can be
      differentiated by morphologic criteria, even on frozen sections during surgery.
      This histologic distinction directs the therapeutic approach because the patients
      experiencing the focal form of the syndrome can be completely cured by a very
      limited pancreatectomy. Molecular findings confirmed the reliability of this
      histologic distinction, showing a specific background for each form.

PMID- 21185998
TI  - Genetics of congenital hyperinsulinemic hypoglycemia.
AB  - A genetic diagnosis is now possible for approximately 45%-55% of patients with
      hyperinsulinemic hypoglycemia. Understanding the genetic etiology of the disease
      in these patients is clinically important because a genetic diagnosis will
      provide information on prognosis, recurrence risk, and importantly may also guide
      clinical management. The aim of this review is to provide an outline of the 7
      different molecular mechanisms underlying this heterogeneous disease and to
      demonstrate that the clinical phenotype can act as a useful guide when
      prioritizing the order of genetic testing.

PMID- 21185999
TI  - KATP channel mutations in congenital hyperinsulinism.
AB  - Adenosine triphosphate (ATP)-sensitive potassium channels (K(ATP) channels) have
      a central role in the regulation of insulin secretion in pancreatic beta cells.
      They are octameric complexes organized around the central core constituted by the
      Kir6.2 subunits. The regulation of the channel itself takes place on the
      sulfonylurea receptor-1 subunit. The channel opens and closes according to the
      balance between adenine nucleotide ATP and adenosine diphosphate.
      Hyperinsulinemic hypoglycemia (also named congenital hyperinsulinism, or CHI) is
      associated with loss-of-function K(ATP) channel mutations. Their frequency
      depends on the histopathological form and the responsiveness of CHI patients to
      diazoxide. ABCC8/KCNJ11 defects are identified in approximately 80% of patients
      with CHI refractory to diazoxide. Within this group, focal forms are related to a
      paternally inherited KCNJ11 or ABCC8 mutation and the loss of the corresponding
      maternal allele in some pancreatic beta cells leading to a focal lesion. Diffuse
      forms are mostly associated with recessively inherited mutations. Some patients
      with diffuse forms also carried a single K(ATP) channel mutation. In contrast,
      K(ATP) mutations are involved in 15% of diazoxide-responsive CHI cases that are
      either sporadic or dominantly inherited.

PMID- 21186000
TI  - Positron emission tomography/computed tomography diagnostics by means of fluorine
      18-L-dihydroxyphenylalanine in congenital hyperinsulinism.
AB  - The unfavorable prognosis of congenital hyperinsulinism (CHI) can be avoided if
      the patients are treated with high-dose glucose infusions and timely surgical
      intervention. Circumscribed foci used to be identified by selective percutaneous
      pancreatic vein catheterization and determination of the insulin level. Fluorine
      18-L-dihydroxyphenylalanine-positron emission tomography (PET) was developed as a
      milder alternative for diagnostic localization of focal disease. The uptake of
      fluorine-18-L-dihydroxyphenylalanine is considerably increased in foci with high
      insulin synthesis rates. In Berlin, diagnosis was achieved by high definition
      PET/computed tomography with multiphase contrast media protocols that provided
      all necessary data with one investigation. We have investigated 135 patients with
      congenital hyperinsulinism, including 45 patients with focal disease (33.3%). All
      the foci were excised on the basis of PET/computed tomography images. The German
      data demonstrate that 87% to 91% of the operated patients could be completely
      healed.

PMID- 21186001
TI  - Visualization of the focus in congenital hyperinsulinism by intraoperative
      sonography.
AB  - In surgery for focal congenital hyperinsulinism (CHI), the identification and
      complete resection of the focus without collateral damage is of utmost
      importance. In a pilot study we applied intra-abdominal high-frequency sonography
      during surgery for focal CHI in 2 infants. The focus could be identified, its
      relation to the pancreatic and common bile duct could be shown, and the typical
      octopus-like tentacles could be demonstrated. In one case the resection was
      successful; in the other it was not. These preliminary results suggest that
      intraoperative sonography could be a valuable tool in the surgical therapy of
      focal CHI and warrants further evaluation in a clinical study.

PMID- 21186002
TI  - A specialized team approach to diagnosis and medical versus surgical treatment of
      infants with congenital hyperinsulinism.
AB  - Hyperinsulinism (HI) is the most common cause of transient and permanent forms of
      hypoglycemia in infancy. Establishing the correct diagnosis and initiating
      appropriate therapy without delay is of utmost importance. Once the diagnosis is
      made and if medical therapy with diazoxide fails, one should assume that the
      infant has a K(ATP) channel defect and may require surgery. In this case, the
      infant should be referred to a center that specializes in HI with 18-fluoro L-3,4
      dihydroxyphenylalanine positron emission tomography scan. This report describes a
      center specializing in HI with a team of experts consisting of endocrinologists,
      nurse practitioners, geneticists, radiologists, pathologists, and a surgeon. It
      describes the center's paradigm for managing severe HI on the basis of more than
      250 cases of HI in the past 10 years, including the diagnosis of HI, medical
      options, genetics of HI, imaging in HI, the surgical approach to HI, and
      outcomes.

PMID- 21186003
TI  - Rare forms of congenital hyperinsulinism.
AB  - Rare forms of congenital hyperinsulinism (CHI) are caused by mutations in GLUD1
      (encoding glutamate dehydrogenase), GCK (encoding glucokinase), HADH (encoding
      for L-3-hydroxyacyl-CoA dehydrogenase), SLC16A1 (encoding the monocarboxylat
      transporter 1), HNF4A (encoding hepatocyte nuclear factor 4alpha) or UCP2
      (encoding mitochondrial uncoupling protein 2). The clinical presentation is very
      heterogeneous in regards to age of onset, severity, and manner of symptoms, as
      well as the response to medical treatment. Special individual characteristics
      have to be accounted in diagnosis and treatment. Diazoxide is the first-line drug
      for the rare forms of CHI for long-term treatment but is not entirely effective
      in some of these rarer defects (GCK, MCT1). The use of diazoxide is often limited
      by side effects and the use of octreotide as second-line drug has to be
      considered. A near-total pancreatectomy is only reserved for patients with
      diffuse disease and resistance to medical treatment as a last resort. Patients
      with CHI should be managed by centers with a highly experienced team in
      diagnostic work-up and treatment of this disease.

PMID- 21186004
TI  - Glucose metabolism and neurological outcome in congenital hyperinsulinism.
AB  - Advances in imaging and surgical techniques allow a complete cure for children
      with focal-type congenital hyperinsulinism (CHI). In contrast, management of
      diffuse-type CHI remains a matter of controversy. To prevent hypoglycemic brain
      damage, extensive surgery has been recommended in the past, resulting in
      diabetes. On the basis of 2 data sets of patients with congenital
      hyperinsulinism, the German registry for CHI with 235 patients (ages 1 day to 19
      years) and the diabetes treatment register (Diabetes Patienten
      Verlaufsdokumentationssystem initiative), a follow-up study was initiated for
      diabetes mellitus and the intellectual and physical development as well as motor
      function. In our ongoing study, we investigated 20 patients with CHI (12 male,
      mean ages 9.9 years). Six of 20 patients had undergone subtotal pancreatectomy.
      In early infantile development (0-3 years) we observed a trend to motor and
      speech delay. In early childhood (2.5-7 years) there appeared a trend to an
      advantage of results of nonverbal tasks compared with verbal tasks. Before 1990
      most patients (~75%) were treated by subtotal pancreatectomy; since 2000, a more
      conservative approach is obvious (4/68). All patients with diabetes (n = 25)
      developed the condition after undergoing subtotal pancreatectomy. No spontaneous
      manifestation of diabetes was noted before adulthood. There was a wide range of
      age (0-17.7 years) at manifestation indicating a long period during which glucose
      tolerance is compensated. Compared with >40.000 children with type 1 diabetes
      mellitus from the Diabetes Patienten-Verlaufsdokumentationssystem registry, we
      found significant differences with a tendency for being overweight as well as
      small stature. Mean daily insulin dose and HbA1c was comparable in both groups.

PMID- 21186005
TI  - Surgical management of congenital hyperinsulinism of infancy.
AB  - Congenital hyperinsulinism of infancy (CHI) is characterized by inappropriate
      insulin secretion resulting in persistent hypoglycemia, which can lead to
      irreversible severe neurological damage in the infant. Many patients with CHI
      will respond to medical therapy, but surgery is necessary in those that do not.
      There are 2 main histologic subtypes, diffuse and focal, both of which may
      require different surgical strategies. Near-total pancreatectomy is the procedure
      of choice for diffuse CHI, whereas a localized resection is curative in focal
      CHI. Open surgery is the traditional approach to pancreatic resection. However,
      laparoscopy is increasingly used, particularly in localized resection for focal
      disease. We describe both methods of pancreatectomy.

PMID- 21186006
TI  - The surgical management of atypical forms of congenital hyperinsulinism.
AB  - Beyond the 2 classical forms of congenital hyperinsulinism, focal and diffuse, we
      report our experience on the surgical treatment of atypical forms. We define 2
      subtypes among these atypical forms of hyperinsulinism: in case of a giant focal
      form the surgical strategy is the same as in focal forms. In case of
      hyperinsulinism caused by a mosaic, our experience suggests the benefit of a
      limited resection from the tail to the body of the pancreas.

PMID- 21186007
TI  - Surgery in congenital hyperinsulinism-tips and tricks not only for surgeons. A
      practical guide.
AB  - Each form of congenital hyperinsulinism (CHI)-focal, diffuse, atypical-requires
      its own surgical strategy and technique. Focal CHI is treated by a positron
      emission tomography/computed tomography-guided, local resection which is confined
      only to the lesion. As much healthy pancreatic tissue as possible is preserved.
      On the contrary, the therapeutic mainstay of diffuse CHI must be conservative
      nowadays. Only in the exceptional cases in which medical treatment fails surgical
      therapy is warranted to prevent hypoglycemia. However, the extension of resection
      that is able to cure hyperinsulinism while avoiding diabetes is not known today.
      The outcome, therefore, is unpredictable. In the rare atypical cases it is
      important to stop the resection at the right time in order not to finish
      unnecessarily with a mutilating operation.

PMID- 21186009
TI  - State of the journal 2011.

PMID- 21186011
TI  - Intraoperative neuromonitoring for early localization and identification of
      recurrent laryngeal nerve during thyroid surgery.
AB  - Early and definite identification of the recurrent laryngeal nerve (RLN) is an
      important step to avoid inadvertent nerve injury during complicated thyroid
      operations. This study aimed to determine the feasibility of routine use of
      intraoperative neuromonitoring (IONM) to localize and identify the RLN at an
      early stage of thyroid surgery. This prospective study enrolled 220 consecutive
      patients (333 RLNs at risk) who underwent thyroid operations with application of
      IONM. The RLN was localized and identified routinely with a nerve stimulator
      after opening the space between the thyroid and carotid sheath. The success rates
      of early RLN localization and identification were evaluated. The current for
      localization and the amplitude of evoked laryngeal electromyographic signals were
      also recorded and analyzed. All RLNs, including 87 (26%) nerves that were
      regarded as difficult to identify, were successfully localized and identified.
      The stimulation level for RLN localization was 2mA in 315 nerves (95%) and 3mA in
      the other 18 nerves (5%). The signal obtained from RLN localization (amplitude =
      932 +/-436MUV) showed a clear and reliable laryngeal electromyographic response
      that was similar to that from direct vagus (amplitude=811+/-389MUV) or RLN
      stimulation (amplitude=1132+/-472MUV). The palsy rate was 0.6% and no permanent
      palsy occurred. RLN injury is rare if the nerve is definitely identified early in
      the thyroid operation. The conclusion of this study is that IONM is a reliable
      tool for early RLN localization and identification, even in complicated thyroid
      operations.

PMID- 21186012
TI  - Electromyographic study of differential sensitivity to succinylcholine of the
      diaphragm, laryngeal and somatic muscles: a swine model.
AB  - Neuromuscular blocking agents (NMBAs) might diminish the electromyography signal
      of the vocalis muscles during intraoperative neuromonitoring of the recurrent
      laryngeal nerve. The aim of this study was to compare differential sensitivity of
      different muscles to succinylcholine in a swine model, and to realize the
      influence of NMBAs on neuromonitoring. Six male Duroc-Landrace piglets were
      anesthetized with thiamylal and underwent tracheal intubation without the use of
      an NMBA. The left recurrent laryngeal nerve, the spinal accessory nerve, the
      right phrenic nerve and the brachial plexus were stimulated. Evoked potentials
      (electromyography signal) of four muscle groups were elicited from needle
      electrodes before and after intravenous succinylcholine bolus (1.0 mg/kg).
      Recorded muscles included the vocalis muscles, trapezius muscle, diaphragm and
      triceps brachii muscles. The onset time and 80% recovery of control response were
      recorded and analyzed. The testing was repeated after 30 minutes. The onset time
      of neuromuscular blocking for the vocalis muscles, trapezius muscle, diaphragm
      and triceps brachii muscle was 36.3 +/- 6.3 seconds, 38.8 +/- 14.9 seconds, 52.5
      +/- 9.7 seconds and 45.0 +/- 8.2 seconds during the first test; and 49.3 +/- 10.8
      seconds, 40.0 +/- 12.2 seconds, 47.5 +/- 11.9 seconds and 41.3 +/- 10.1 seconds
      during the second test. The 80% recovery of the control response for each muscle
      was 18.3 +/- 2.7 minutes, 16.5+/-6.9 minutes, 8.1+/-2.5 minutes and 14.8+/-2.9
      minutes during the first test; and 21.5+/-3.8 minutes, 12.5 +/- 4.3 minutes, 10.5
      +/- 3.1 minutes and 16.4 +/- 4.2 minutes during the second test. The sensitivity
      of the muscles to succinylcholine, ranked in order, was: the vocalis muscles, the
      triceps brachii muscle, the trapezius muscle and the diaphragm. We demonstrated a
      useful and reliable animal model to investigate the effects of NMBAs on
      intraoperative neuromonitoring. Extrapolation of these data to humans should be
      done with caution.

PMID- 21186013
TI  - Immigration distress and associated factors among Vietnamese women in
      transnational marriages in Taiwan.
AB  - The purpose of this study was to explore the types and predictors of immigration
      distress among Vietnamese women in transnational marriages in Taiwan. A cross
      sectional survey with face-to-face interviews was conducted for data collection.
      A convenient sample of 203 Vietnamese women in transnational marriages in
      southern Taiwan was recruited. The Demographic Inventory measured the
      participants' age, education, employment status, religion, length of residency
      and number of children, as well as their spouse's age, education, employment
      status and religion. The Demand of Immigration Specific Distress scale measured
      the level of distress and had six subscales: loss, novelty, occupational
      adjustment, language accommodation, discrimination and alienation. Among the 203
      participants, 6.4% had a high level of immigration distress; 91.1% had moderate
      distress; and 2.5% had minor distress. Higher mean scores were found for the
      loss, novelty and language accommodation subscales of the Demand of Immigration
      Specific Distress scale. Participant's (r = 0.321, p < 0.01) and spouse's (r =
      0.375, p < 0.01) unemployment, and more children (r = 0.129, p < 0.05) led to
      greater immigration distress. Length of residency in Taiwan (r = 0.576, p <
      0.001) was an effective predictor of immigration distress. It indicated that the
      participants who had stayed fewer years in Taiwan had a higher level of immigrant
      distress. Health care professionals need to be aware that the female newcomers in
      transnational marriages are highly susceptible to immigration distress. The study
      suggests that healthcare professionals need to provide a comprehensive assessment
      of immigration distress to detect health problems early and administer culturally
      appropriate healthcare for immigrant women in transnational marriages.

PMID- 21186014
TI  - Anorectal malignant melanomas: experience of Uludag University.
AB  - Anorectal melanomas represent a group of mucosal melanomas with unknown etiology
      and poor prognosis. The lesions can be misdiagnosed as hemorrhoids during
      clinical examination. We reviewed the morphological and clinical features of 14
      anorectal melanomas, and discuss the treatment modalities of this entity.
      Fourteen patients who were diagnosed with anorectal malignant melanoma between
      1997 and 2004 were evaluated with regard to age, sex, size, morphology, lymph
      node or distant metastasis, treatment modality and survival. Eight patients were
      female and six were male, and their mean age was 58 years. The size of melanoma
      ranged from 3 cm to 8 cm. Pathological evaluation revealed epithelioid and
      spindle cell type tumor in seven and two patients, respectively, whereas, in the
      remaining seven patients, the tumor was composed of both types. Pigmentation was
      apparent in all tumors. There was lymph node metastasis in 11 patients and
      distant metastasis in all patients. Eleven patients underwent abdominoperineal
      resection and three were treated by local excision. Mean survival was 8.7 months.
      Prognosis of anorectal melanoma remains poor. Awareness of the diverse
      clinicopathological features of these lesions, both on the part of the clinicians
      and pathologists, is crucial for their early detection and proper treatment.

PMID- 21186015
TI  - Multiple organ infarctions following disseminated intravascular coagulation
      precipitated by sepsis in a healthy infant: a case report.
AB  - Multiple organ infarctions are a very rare clinical event in children. We report
      a 3-month-old infant with sepsis and disseminated intravascular coagulation, who
      was diagnosed with cerebral ischemic stroke associated with middle cerebral
      artery stenosis and subsequent retinal infarction by magnetic resonance imaging,
      fundoscopy and magnetic resonance angiography. In addition, he suffered from
      renal infarction with hypertension and was treated until 1 year of age. We
      emphasize the importance of early recognition of organ infarctions, prophylaxis
      of risk factors and of optimized therapy of the underlying etiology.

PMID- 21186016
TI  - Subcutaneous emphysema, pneumothorax, pneumomediastinum, and pneumoperitoneum
      during colonoscopic balloon dilation: a case report.
AB  - A 77-year-old woman underwent colonoscopic balloon dilatation for colonic
      stricture 1 year after laparoscopic anterior resection of sigmoid colon cancer.
      During the balloon dilatation, panfacial swelling and apnea were noted. Emergency
      endotracheal intubation was undertaken. Chest X-ray revealed diffuse subcutaneous
      emphysema and bilateral pneumothorax. We discuss the possible mechanism and
      management of this uncommon complication during therapeutic colonoscopy.

PMID- 21186017
TI  - Malignant melanoma of the choroid in the eye with oculodermal melanocytosis of a
      Chinese woman.
AB  - In this study, we report a rare case of choroidal melanoma in an eye with
      oculodermal melanocytosis (Nevus of Ota). A 56-year-old Taiwanese woman with
      oculodermal melanocytosis in the right eye was found to have an ipsilateral uveal
      melanoma. Histopathology of the enucleated eye confirmed the diagnosis of
      malignant choroidal melanoma of mixed cell type. A search of the literature
      revealed strong evidence that oculodermal melanocytosis can predispose to the
      development of uveal melanoma in Caucasians. Only seven such cases have been
      reported in the East Asian population. This is believed to be the first such
      reported case in a patient of Chinese descent.

PMID- 21186018
TI  - Spontaneous internal jugular vein thrombosis: a case report.
AB  - Internal jugular vein thrombosis (IJVT) is an elusive vascular disease that is
      rarely seen, with potentially lethal complications such as sepsis and pulmonary
      embolism. Spontaneous IJVT is considered when no apparent predisposing cause of
      thrombosis is present. A previously healthy, 31-year-old woman presented to the
      university-based emergency department because of painless swelling in the right
      anterior side of her neck. Physical examination revealed a painless, soft and
      immobile mass in the right anterior side of her neck beneath the
      sternocleidomastoid muscle, without hyperemia or local heat. On ultrasonographic
      examination, a hyperechogenic mass was visualized around the thoracic entrance of
      the right internal jugular vein, which was suggestive of a thrombus. The patient
      was administered intravenous antibiotic and low-molecular-weight heparin followed
      by oral coumadin as anticoagulant therapy. Her complaints were relieved within 5
      days. She was completely well after 6 months. Venous thrombosis generally results
      from impaired blood flow locally or systemically that leads to activation of
      coagulation. Primary care physicians should sustain a high index of suspicion in
      patients who present with undiagnosed swelling in the neck, or other signs and
      symptoms attributed to IJVT.

PMID- 21186019
TI  - Description- and experience-based choice: does equivalent information equal
      equivalent choice?
AB  - Does the manner in which people acquire information affect their choices? Recent
      research has contrasted choices based on summary descriptions (e.g. a 100% chance
      of $3 vs. an 80% chance of $4) with those based on the 'experience' of drawing
      samples from environments that do (or should) match those provided by
      descriptions. Intriguingly, decision-makers' preferences differ markedly across
      the two formats: the so-called description-experience "gap" - but debate over the
      cause of this gap continues. We employed novel techniques to ensure strict
      control over both external and internal biases in the samples of information that
      people used to make decisions from experience. In line with some other recent
      research, we found a much diminished gap in both experiments suggesting that the
      divergence in choices based on description and sequentially acquired (non
      consequential) samples is largely the result of non-equivalent information at the
      point of choice. The implications for models of risky choice are discussed.

PMID- 21186020
TI  - VDR deficiency affects alveolar bone and cementum apposition in mice.
AB  - OBJECTIVE: To compare the mineralisation density (MD), morphology and histology
      of alveolar bone and cementum amongst VDR +/+, VDR -/-, and VDR -/- groups
      supplemented with a diet TD 96348, containing 20% lactose, 2.0% calcium and 1.25%
      phosphorous. METHODS: Four groups of mice (6 mice/group) were identified by
      genotyping: VDR +/+ mice (VDR wild type), VDR -/- mice (VDR deficient), VDR -/-
      offsprings derived from VDR -/- parents receiving a supplemental diet (early
      rescued), and VDR -/- mice fed with a supplemental diet beginning at age one
      month (late rescued). All mice were sacrificed at age 70.5 days. Micro-CT was
      used to compare MD and morphology of alveolar bone and cementum. H-E and
      Toluidine blue staining was used to examine the ultrastructure of the alveolar
      bone and cementum at matched locations. RESULTS: In VDR -/- group, alveolar bone
      and cementum failed to mineralise normally. Early rescue increased MD of alveolar
      bone in VDR -/- mice with excessive alveolar bone formation, but which not
      observed in late rescue group. MD and morphology of cementum-dentine complex in
      both early and late rescue groups were comparable with VDR +/+ group when feeding
      with high-calcium rescue diet. CONCLUSIONS: VDR affects alveolar bone
      mineralisation and formation systemically and locally. However, cementum
      apposition and mineralisation is mainly regulated by calcium concentrations in
      serum.

PMID- 21186021
TI  - The learnability of abstract syntactic principles.
AB  - Children acquiring language infer the correct form of syntactic constructions for
      which they appear to have little or no direct evidence, avoiding simple but
      incorrect generalizations that would be consistent with the data they receive.
      These generalizations must be guided by some inductive bias - some abstract
      knowledge - that leads them to prefer the correct hypotheses even in the absence
      of directly supporting evidence. What form do these inductive constraints take?
      It is often argued or assumed that they reflect innately specified knowledge of
      language. A classic example of such an argument moves from the phenomenon of
      auxiliary fronting in English interrogatives to the conclusion that children must
      innately know that syntactic rules are defined over hierarchical phrase
      structures rather than linear sequences of words (e.g., Chomsky, 1965, 1971,
      1980; Crain & Nakayama, 1987). Here we use a Bayesian framework for grammar
      induction to address a version of this argument and show that, given typical
      child-directed speech and certain innate domain-general capacities, an ideal
      learner could recognize the hierarchical phrase structure of language without
      having this knowledge innately specified as part of the language faculty. We
      discuss the implications of this analysis for accounts of human language
      acquisition.

PMID- 21186022
TI  - Fire and soils: methodological issues and implications to management.

PMID- 21186023
TI  - Menstrual effects among women exposed to polychlorinated biphenyls and
      dibenzofurans.
AB  - BACKGROUND: Polychlorinated biphenyls (PCBs), dibenzofurans (PCDFs), and dibenzo
      dioxins (PCDDs) may affect the female reproductive system in humans. A mass
      poisoning occurred in Taiwan due to PCBs/PCDFs-contaminated cooking oil, and was
      called the Yucheng (oil-disease in Chinese). We aimed to determine whether
      Yucheng women were affected in their menstruation. METHODS: After the event, we
      followed the exposed individuals and an age-matched neighborhood reference group.
      Menstrual cycle characteristics and age at menarche were obtained by a telephone
      interview. We used multiple linear and logistic regression to examine the
      association between PCBs/PCDFs and menstrual cycle characteristics, after
      adjusting for confounding factors. RESULTS: Totally 445 women responded
      satisfactorily and were included in the analyses of menstrual characteristics.
      Menstrual cycle irregularity and dysmenorrheal did not differ between Yucheng and
      referents. Yucheng women's menstrual cycles were 0.5 (95% CI: 0.0-0.5; p=0.03)
      days shorter than those of the referents. The Yucheng women with skin lesions
      caused by PCBs/PCDFs were more prominently affected, with the cycles 1.2 days
      shorter than the referents. Yucheng women exposed to PCBs/PCDFs at the
      premenacheal period had reduced cycle length (-0.7 day, 95% CI: -1.4 to 0.0;
      p=0.04) and longer days of menstrual flow (0.5 day, 95% CI: 0.0-1.0; p=0.04).
      Among those women who were exposed at an age of 5-9 years, menarche started
      slightly earlier with borderline significance. CONCLUSIONS: Shorter menstrual
      cycle length and a longer duration of bleeding in each cycle were found among
      women previously exposed to PCBs/PCDFs. These effects were more obviously
      observed among those exposed at premenarcheal ages.

PMID- 21186024
TI  - Takagi-Sugeno control of nocturnal temperature in greenhouses using air heating.
AB  - A solution to the problem of controlling the minimum temperature in greenhouses
      using controllers developed from nonlinear models of the system is discussed and
      applied on a real greenhouse. More precisely, the controllers designed are Takagi
      Sugeno type controllers, and the proposed design method is an iterative method
      based on solving a set of Linear Matrix Inequalities, which ensures stability and
      performance in closed-loop. The tests in a real greenhouse show that it is
      possible to design controllers for control of nocturnal temperature that give
      good performance, and guarantee stability in a wide range of working conditions.

PMID- 21186025
TI  - Musculo - ske Wii tal medicine.

PMID- 21186026
TI  - Nutraceutical antioxidants for vascular protection? Please mind regression toward
      the mean.

PMID- 21186027
TI  - Vertical ground reaction forces diminish in mice after botulinum toxin injection.
AB  - We examined changes in weight-bearing ability in mice after injection with
      botulinum toxin type A (BTX) to determine whether BTX can be used to isolate the
      effects of muscle on bone. As ambulation patterns were previously shown to
      improve within two weeks post-injection, we hypothesized that BTX injection to
      the posterior hindlimb would not significantly affect the mouse's ability to bear
      weight in the affected limb one week post-injection. Female BALB/c mice (N=13, 16
      17 week old) were injected with either 20 MUL of BTX (1U/100 g) or saline (SAL)
      in the left posterior hindlimb. Vertical ground reaction forces (GRF), hindlimb
      muscle cross-sectional area (MCSA), and tibial bone micro-architecture were
      assessed for 42 d following injection. Peak and average vertical GRF were 11+/-1%
      and 23+/-3% lower, respectively, in the BTX-injected hindlimb within 4d post
      injection and remained lower than the SAL-injected hindlimb 14-21 d post
      injection (15+/-4% and 10+/-2%, respectively). Time between forelimb and hindlimb
      peaks was 30-40% greater in the BTX-injected hindlimb than SAL-injected hindlimb
      4-14 d post-injection. Peak vertical GRF recovered earlier following BTX
      injection than MCSA or bone volume fraction. These results indicate that weight
      bearing ability recovered despite persistent muscle atrophy, and that weight
      bearing alone was insufficient to maintain bone in the absence of muscle
      activity. We suggest that the absence of high-frequency signals typically
      associated with fast-twitch muscle activity may be contributing to the ongoing
      degradation of bone after BTX injection.

PMID- 21186028
TI  - Determination of decamethylcyclopentasiloxane in river and estuarine sediments in
      the UK.
AB  - Robust analytical procedures for the measurement of decamethylcyclopentasiloxane
      (D5) in river and estuarine sediments and their application in determining
      environmental concentrations in the UK are presented for the first time in this
      work. Novel approaches to minimise commonly reported artefacts are utilised,
      improving the confidence in the concentrations of D5 reported. Accelerated
      solvent extraction (ASE) and liquid-solid extraction methods are compared. Both
      methods use on-column injection gas chromatography/mass spectrometry (GC/MS).
      Measurements of D5 concentrations in sediments sampled from the river Great Ouse
      and from the Humber estuary (UK) are also reported. ASE was suitable to measure
      concentrations of D5 in sediments obtained from the river Great Ouse, UK (186
      1450 ng g-1, dry weight) and octamethyltetracyclosiloxane (D4, 12-24 ng g-1, dry
      weight). C12 linear alkybenzene (C12 LAB), which can be used as a chemical marker
      for sewage effluent related emissions, was also measured in this analysis. Liquid
      solid extraction was optimised to provide more confidence in the lower D5
      concentrations measured in the Humber estuary, UK (49-256 ng g-1, dry weight). A
      Limit of quantitation (LOQ) for D5 of 57-110 and 4 ng g-1 dry weight was
      determined for ASE and liquid-solid extraction, respectively.

PMID- 21186029
TI  - On-line solid-phase extraction coupled to hydrophilic interaction chromatography
      mass spectrometry for the determination of polar drugs.
AB  - The present study describes the first fully automated method based on on-line
      solid-phase extraction (SPE) coupled to hydrophilic interaction chromatography
      electrospray-mass spectrometry (HILIC-(ESI)MS) to determine a group of polar
      drugs that includes illicit drugs (such as cocaine, morphine, codeine and
      metabolites) and pharmaceuticals in environmental water samples. The SPE was
      performed using a highly retentive polymeric sorbent. The HILIC separation was
      optimised and the initial high organic content of the chromatographic mobile
      phase, was also suitable for the proper on-line elution of the analytes retained
      in the SPE column and for enhancing the ESI ionisation efficiency. This method
      allows the loading of samples of up to 250ml of ultrapure water or 10ml of
      environmental water samples spiked at low ngl(-1) levels of the analytes. The
      method yields near 100% recoveries for all the analytes. The method was also
      validated with environmental water samples with linear ranges from 5 to 1000ngl(
      1) and limits of detection <=2ngl(-1) for most of the compounds.

PMID- 21186030
TI  - Selectivity of monolithic supports under overloading conditions and their use for
      separation of human plasma and isolation of low abundance proteins.
AB  - Human serum albumin (HSA) and immunoglobulin G (IgG) represent over 75% of all
      proteins present in human plasma. These two proteins frequently interfere with
      detection, determination and purification of low abundance proteins that can be
      potential biomarkers and biomarker candidates for various diseases. Some low
      abundance plasma proteins such as clotting factors and inhibitors are also
      important therapeutic agents. In this paper, the characterization of ion-exchange
      monolithic supports under overloading conditions was performed by use of sample
      displacement chromatography (SDC). If these supports were used for separation of
      human plasma, the composition of bound and eluted proteins in both anion- and
      cation-exchange mode is dependent on column loading. Under overloading
      conditions, the weakly bound proteins such as HSA in anion-exchange and IgG in
      cation-exchange mode are displaced by stronger binding proteins, and this
      phenomenon was not dependent on column size. Consequently, small monolithic
      columns with a column volume of 100 and 200 MUL are ideal supports for high
      throughput screening in order to develop new methods for separation of complex
      mixtures, and for sample preparation in proteomic technology.

PMID- 21186031
TI  - Thioether-functionalized mesoporous fiber membranes: sol-gel combined electrospun
      fabrication and their applications for Hg2+ removal.
AB  - Mesoporous polyvinylpyrrolidone (PVP)/SiO(2) composite nanofiber membranes
      functionalized with thioether groups have been fabricated by a combination method
      of sol-gel process and electrospinning. The precursor sol was synthesized by one
      step co-condensation of tetraethyl orthosilicate (TEOS) and 1,4
      bis(triethoxysilyl)propane tetrasulfide (BTESPTS, (CH(3)CH(2)O)(3)Si(CH(2))(3)S-S
      S-S(CH(2))(3)Si-(OCH(2)CH(3))(3)), with the triblock copolymer poly(ethylene
      oxide)-poly(propylene oxide)-poly(ethylene oxide) (P123, EO(20)PO(70)EO(20)) as
      template. After the addition of PVP, nanofiber membranes were prepared by
      electrospinning. The membranes were characterized by scanning electron microscopy
      (SEM), high-resolution transmission electron microscopy (HRTEM) images, X-ray
      diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), N(2)
      adsorption-desorption isotherms, and an Elementar Vario EL analyzer. The
      composites were used as highly selective adsorbents for Hg(2+) due to the
      modification with thioether groups (-S-), and were conveniently separated from
      the waste water. The composite could be regenerated through acidification.

PMID- 21186032
TI  - Fine tuning of the morphology of copper oxide nanostructures and their
      application in ambient degradation of methylene blue.
AB  - In this work, flower-like, boat-like, plate-like and ellipsoid-like copper oxide
      (CuO) nanostructures were fabricated by simple modulation of reaction conditions.
      X-ray diffraction, scanning electron microscopy, transmission electron
      microscopy, selected area electron diffraction, nitrogen adsorption-desorption
      measurements and UV-visible diffuse reflectance spectra were employed to
      characterize the obtained CuO nanostructures. Reactants, hydrothermal temperature
      and time were found to largely affect the morphology and structure of CuO
      nanostructures. Flower-like and boat-like CuO nanostructures were successively
      fabricated by increasing hydrothermal time. Plate-like and ellipsoid-like CuO
      nanostructures were produced by modulating the use of polyethylene glycol (PEG)
      and NH(3).H(2)O. The formation mechanisms were proposed based on the experimental
      results, which show that both PEG and NH(3).H(2)O play an important role in the
      formation of the morphology and structure of CuO. The catalytic activity of the
      as-prepared CuO nanostructures was demonstrated by catalytic oxidation of
      methylene blue (MB) in presence of hydrogen peroxide (H(2)O(2)). The as-prepared
      CuO nanostructures all show good catalytic activity.

PMID- 21186033
TI  - Thiocyanate removal from aqueous solution by a synthetic hydrotalcite sol.
AB  - The use of a chloride-containing synthetic hydrotalcite sol (LDHC) as adsorbent
      to remove thiocyanate from aqueous solution was investigated. LDHC was prepared
      by coprecipitation and was characterized by HRTEM, particle size, XRD, and FTIR.
      The experiments showed that LDHC was particularly effective in removing
      thiocyanate due to its small particle size and high zeta potential. The
      adsorption of thiocyanate on LDHC was favored when the initial solution pH was in
      the range 3-10, though the most effective pH range was between 4.0 and 8.0. The
      adsorption reached equilibrium within 150 min. The interaction between the
      surface sites of LDHC and thiocyanate ions may be a combination of both anion
      exchange and surface complexation. The pseudo-second-order model best described
      the adsorption kinetics of thiocyanate onto LDHC. The equilibrium isotherm showed
      that the adsorption of thiocyanate on LDHC was consistent with the Langmuir
      equation and the saturated adsorption capacity of LDHC for thiocyanate was 98.3
      mg/g at 20 degrees C. The regenerated LDHC in FeCl(3) solution can be used
      repeatedly in adsorption-regeneration cycles. The results showed that LDHC can be
      used as a new adsorbent for thiocyanate removal from aqueous solution because of
      its high adsorption capacity and rapid adsorption rate.

PMID- 21186034
TI  - The fabrication of one-dimensional Ca4Y6(SiO4)6O: Ln3+ (Ln=Eu, Tb) phosphors by
      electrospinning method and their luminescence properties.
AB  - One-dimensional Ca(4)Y(6)(SiO(4))(6)O: Ln(3+) (Ln=Eu, Tb) microfibers were
      fabricated by a simple and cost-effective electrospinning method. X-ray
      diffraction (XRD) pattern and high-resolution transmission electron microscopy
      (HRTEM) confirmed that the fibers were composed of hexagonal Ca(4)Y(6)(SiO4)(6)O
      phase. Thermogravimetric and differential scanning calorimetry (TG-DSC) results
      showed that the Ca(4)Y(6)(SiO4)(6)O phase began to crystallize at 740 degrees C.
      Scanning electron microscopy (SEM) and transmission electron microscopy (TEM)
      results indicated that the diameter of as-prepared microfibers ranged from 390 to
      900 nm and the diameter of the microfibers annealed at 1000 degrees C ranged from
      to 120 to 260 nm. Under ultraviolet and low-voltage electron beams (3-5 kV)
      excitation, the Ca(4)Y(6)(SiO(4))(6)O: Ln(3+) (Ln=Eu, Tb) samples showed the red
      and green emission, corresponding to (5)D(0)->(7)F(2) transition of Eu(3+) and
      (5)D(4)->(7)F(5) transition of Tb(3+), respectively.

PMID- 21186035
TI  - Self-aggregation and antimicrobial activity of imidazolium and pyridinium based
      ionic liquids in aqueous solution.
AB  - Two series of long-chain imidazolium and pyridinium based ionic liquids (1-alkyl
      3-methylimidazolium and 1-alkylpyridinium bromides) were synthesised and the
      effect of the alkyl chain length and the nature of the cationic head group on
      micellization and antimicrobial activity of the ionic liquids (ILs) were
      investigated. Tensiometry, conductometry, spectrofluorimetry and PGSE-NMR were
      applied to study the self-aggregation of the amphiphilic ILs in aqueous solution.
      The ILs investigated displayed surface activity and the characteristic chain
      length dependence of the micellization process of surfactants. The antimicrobial
      activity was evaluated against Gram-negative and Gram-positive bacteria and
      fungi. ILs containing more than eight carbon atoms in the alkyl chain showed
      antimicrobial activity. Their efficiency as antimicrobial agents increased with
      the hydrophobicity of the amphiphilic cation being the C(14) homologous the most
      active compounds.

PMID- 21186036
TI  - [Brachial plexus sleep palsy].
AB  - INTRODUCTION: Brachial plexus is rarely involved in "Saturday night palsy". CASE
      REPORT: A young man was admitted for numbness and weakness of his right upper
      limb after awaking from sleep. Neurophysiological studies, consistent with
      brachial plexopathy, revealed presence of proximal conduction blocks. Patient
      presented spontaneous clinical and neurophysiological improvement. DISCUSSION:
      Diagnosis of compressive brachial plexopathy needs to eliminate other causes of
      neuropathy with conduction block.

PMID- 21186038
TI  - The effect of initial stress on the propagation behavior of SH waves in
      piezoelectric coupled plates.
AB  - This study analytically investigates the propagation of shear waves (SH waves) in
      a coupled plate consisting of a piezoelectric layer and an elastic layer with
      initial stress. The piezoelectric material is polarized in z-axis direction and
      perfectly bonded to an elastic layer. The mechanical displacement and electrical
      potential function are derived for the piezoelectric coupled plates by solving
      the electromechanical field equations. The effects of the thickness ratio and the
      initial stress on the dispersion relations and the phase and group velocities are
      obtained for electrically open and mechanically free situations. The numerical
      examples are provided to illustrate graphically the variations of the phase and
      group velocities versus the wave number for the different layers comparatively.
      It is seen that the phase velocity of SH waves decreases with the increase of the
      magnitude of the initial compression stress, while it increases with the increase
      of the magnitude of the initial tensile stress. The initial stress has a great
      effect on the propagation of SH waves with the decrease of the thickness ratio.
      This research is theoretically useful for the design of surface acoustic wave
      (SAW) devices with high performance.

PMID- 21186037
TI  - [Vitamin D and multiple sclerosis. A prospective survey of patients of Poitou
      Charentes area].
AB  - INTRODUCTION: Recent reports demonstrate the implication of vitamin D in multiple
      sclerosis (MS). METHODS: In a multicentric regional study (Poitou-Charentes area)
      during the first trimester 2010, we measured the 25-OH vitamin D serum level in
      170 consecutive MS patients, and in 170 controls matched for age (+/-4 years),
      sex and date of blood sample analysis. We searched for correlations between 25-OH
      vitamin D serum levels and the MS form, the disability (EDSS), the relapse rate
      during the previous year and the presence and number of enhancing lesions on T1
      weighted MRI dating less than 12 months in relapsing MS. RESULTS: Hypovitaminosis
      D was very frequent in MS patients and 25-OH vitamin D serum level was
      significantly lower (14.5 +/- 9.2 mcg/mL) in MS patients than in the control
      group (16.7 +/- 9.6 mcg/mL). This serum level was inversely correlated with the
      degree of disability measured with EDSS score and was lower in secondary
      progressive (RR-SP) and primary progressive (PP) MS than in relapsing MS (RR). No
      correlation was found between 25-OH vit D serum level and relapse rate during the
      previous year in RR MS and the presence and number of enhancing lesions on T1
      weighted MRI dating from less than 12 months. CONCLUSION: 25-OH vit D serum level
      is very low in MS, mainly in RR-SP and PP MS and is correlated with disability.
      This suggests MS patients should be screened for vitamin D deficiency and given
      supplementation systematically when hypovitaminosis D is discovered.

PMID- 21186039
TI  - A new standing-wave-type linear ultrasonic motor based on in-plane modes.
AB  - This paper presents a new standing-wave-type linear ultrasonic motor using
      combination of the first longitudinal and the second bending modes. Two
      piezoelectric plates in combination with a metal thin plate are used to construct
      the stator. The superior point of the stator is its isosceles triangular
      structure part of the stator, which can amplify the displacement in horizontal
      direction of the stator in perpendicular direction when the stator is operated in
      the first longitudinal mode. The influence of the base angle theta of the
      triangular structure part on the amplitude of the driving foot has been analyzed
      by numerical analysis. Four prototype stators with different angles theta have
      been fabricated and the experimental investigation of these stators has validated
      the numerical simulation. The overall dimensions of the prototype stators are no
      more than 40 mm (length) * 20 mm (width) * 5 mm (thickness). Driven by an AC
      signal with the driving frequency of 53.3 kHz, the no-load speed and the maximal
      thrust of the prototype motor using the stator with base angle 20 degrees  were
      98 mm/s and 3.2N, respectively. The effective elliptical motion trajectory of the
      contact point of the stator can be achieved by the isosceles triangular structure
      part using only two PZTs, and thus it makes the motor low cost in fabrication,
      simple in structure and easy to realize miniaturization.

PMID- 21186040
TI  - Radial transport processes as a precursor to particle deposition in drinking
      water distribution systems.
AB  - Various particle transport mechanisms play a role in the build-up of
      discoloration potential in drinking water distribution networks. In order to
      enhance our understanding of and ability to predict this build-up, it is
      essential to recognize and understand their role. Gravitational settling with
      drag has primarily been considered in this context. However, since flow in water
      distribution pipes is nearly always in the turbulent regime, turbulent processes
      should be considered also. In addition to these, single particle effects and
      forces may affect radial particle transport. In this work, we present an
      application of a previously published turbulent particle deposition theory to
      conditions relevant for drinking water distribution systems. We predict
      quantitatively under which conditions turbophoresis, including the virtual mass
      effect, the Saffman lift force, and the Magnus force may contribute significantly
      to sediment transport in radial direction and compare these results to
      experimental observations. The contribution of turbophoresis is mostly limited to
      large particles (>50 MUm) in transport mains, and not expected to play a major
      role in distribution mains. The Saffman lift force may enhance this process to
      some degree. The Magnus force is not expected to play any significant role in
      drinking water distribution systems.

PMID- 21186041
TI  - Transformation of the antiepileptic drug oxcarbazepine upon different water
      disinfection processes.
AB  - Transformation of the pharmaceutical oxcarbazepine (OXC), a keto analogue of
      carbamazepine (CBZ) was investigated under different water disinfection processes
      (ozonation, chlorination and UV irradiation) to compare its persistence, toxicity
      and degradation pathways with those of CBZ. Analysis by LC-ion trap-MS(n) allowed
      for the identification of up to thirteen transformation products (TPs). The major
      abundant and persistent TPs (10,11-dihydro-10,11-trans-dihydroxy-carbamazepine
      (DiOH-CBZ), acridine (ACIN) and 1-(2-benzaldehyde)-(1H, 3H)-quinazoline-2,4-dione
      (BQD)) were identical to those previously reported during water treatment of CBZ.
      Only one new compound arising from an intramolecular cyclisation reaction was
      identified during UV irradiation. OXC reacted quickly with hydroxyl radical and
      relatively rapidly with free chlorine while slow reaction rates were recorded in
      presence of ozone and upon UV irradiation. An increase of the acute toxicity of
      UV irradiated solutions, monitored by a Daphnia magna bioassay, was recorded,
      probably due to the accumulation of ACIN. The formation of ACIN is of concern due
      to the carcinogenic properties of this chemical. ACIN was also generated during
      the direct UV photo transformation of DiOH-CBZ and 10-hydroxy-10,11-dihydro
      carbamazepine (OH-CBZ), two metabolites of OXC and CBZ widely detected in water
      resources. Analysis of tap water samples revealed the occurrence at ng/L levels
      of the major TPs detected under laboratory scale experiments, except ACIN.

PMID- 21186042
TI  - Exploiting a new electrochemical sensor for biofilm monitoring and water
      treatment optimization.
AB  - Bacterial biofilm development is a serious problem in many fields, and the
      existing biofilm monitoring sensors often turn out to be inadequate. In this
      perspective, a new sensor (ALVIM) has been developed, exploiting the natural
      marine and freshwater biofilms electrochemical activity, proportional to surface
      covering. The results presented in this work, obtained testing the ALVIM system
      both in laboratory and in an industrial environment, show that the sensor gives a
      fast and accurate response to biofilm growth, and that this response can be used
      to optimize cleaning treatments inside pipelines. Compared to the existing
      biofilm sensors, the proposed system show significant technological innovations,
      higher sensitivity and precision.

PMID- 21186043
TI  - Small molecule inhibitors of histone acetyltransferase Tip60.
AB  - Tip60 is a key member of the MYST family of histone acetyltransferases and
      involved in a broad spectrum of cellular pathways and disease conditions. So far,
      small molecule inhibitors of Tip60 and other members of MYST HATs are rarely
      reported. To discover new small molecule inhibitors of Tip60 as mechanistic tools
      for functional study and as chemical leads for therapeutic development, we
      performed virtual screening using the crystal structure of Esa1 (the yeast
      homolog of Tip60) on a small molecule library database. Radioactive acetylation
      assays were carried out to further evaluate the virtual screen hits. Several
      compounds with new structural scaffolds were identified with micromolar
      inhibition potency for Tip60 from the biochemical studies. Further, computer
      modeling and kinetic assays suggest that these molecules target the acetyl-CoA
      binding site in Tip60. These new inhibitors provide valuable chemical hits to
      develop further potent inhibitors for the MYST HATs.

PMID- 21186044
TI  - Selective redox degradation of chlorinated aliphatic compounds by Fenton reaction
      in pyrite suspension.
AB  - Selective redox degradation of chlorinated aliphatics by Fenton reaction in
      pyrite suspension was investigated in a closed system. Carbon tetrachloride (CT)
      was used as a representative target of perchlorinated alkanes and
      trichloroethylene (TCE) was used as one of highly chlorinated alkenes.
      Degradation of CT in Fenton reaction was significantly enhanced by pyrite used as
      an iron source instead of soluble Fe. Pyrite Fenton showed 93% of CT removal in
      140 min, while Fenton reaction with soluble Fe(II) showed 52% and that with
      Fe(III) 15%. Addition of 2-propanol to the pyrite Fenton system significantly
      inhibited degradation of TCE (99% to 44% of TCE removal), while degradation of CT
      was slightly improved by the 2-propanol addition (80-91% of CT removal). The
      result suggests that, unlike oxidative degradation of TCE by hydroxyl radical in
      pyrite Fenton system, an oxidation by the hydroxyl radical is not a main
      degradation mechanism for the degradation of CT in pyrite Fenton system but a
      reductive dechlorination by superoxide can rather be the one for the CT
      degradation. The degradation kinetics of CT in the pyrite Fenton system was
      decelerated (0.13-0.03 min(-1)), as initial suspension pH decreased from 3 to 2.
      The formation of superoxide during the CT degradation in the pyrite Fenton system
      was observed by electron spin resonance spectroscopy. The formation at initial pH
      3 was greater than that at initial pH 2, which supported that superoxide was a
      main reductant for degradation of CT in the pyrite Fenton system.

PMID- 21186045
TI  - Concentrations of polychlorinated biphenyls in water from US Lake Ontario
      tributaries between 2004 and 2008.
AB  - Research on the environmental fate and transport of PCBs in Lake Ontario basin
      depends, among other aspects, on the availability of representative data sets for
      upstream sources, but data are lacking for most US Lake Ontario tributaries. In
      this study, water samples were collected between September 2004 and October 2008
      from five tributaries and were analyzed for 209 polychlorinated biphenyls (PCB)
      with high-resolution gas chromatography/high resolution mass spectrometry
      (HRGC/HRMS) following EPA Method 1668 A. Total PCB concentrations ranged between
      0.31 and 42.75 ng L(-1). Congeners between Di and Hexa PCBs accounted between 70
      and 99% of the total PCB. The tributary with highest PCB concentrations presented
      similar pattern and percentage levels to Aroclor 1242. Total average loads for
      the sampling events ranged between 1.85 g d(-1) and 59.08 g d(-1). PCB
      concentrations were evaluated against other variables and other studies
      (including different matrices) to better understand their transport. The
      methodology used is reliable to assess PCB contamination in surface water.

PMID- 21186046
TI  - Effects of bioturbation on the fate of oil in coastal sandy sediments--an in situ
      experiment.
AB  - Effects of bioturbation by the common lugworm Arenicola marina on the fate of oil
      hydrocarbons (alkanes and PAHs) were studied in situ during a simulated oil spill
      in a shallow coastal area of Roskilde fjord, Denmark. The fate of selected oil
      compounds was monitored during 120 d using GC-MS and bioturbation activity (feces
      production and irrigation) was measured regularly during the experiment and used
      as input parameters in a mechanistic model describing the effects of A. marina on
      the transport and degradation of oil compounds in the sediment. The chemical
      analytical data and model results indicated that A. marina had profound and
      predictable effects on the distribution, degradation and preservation of oil and
      that the net effect depended on the initial distribution of oil. In sediment with
      an oil contaminated subsurface-layer A. marina buried the layer deeper in the
      sediment which clearly enhanced oil persistence. Conversely, A. marina stimulated
      both the physical removal and microbial degradation of oil compounds in uniformly
      oil contaminated sediments especially in deeper sediment layers (10-20 cm below
      the surface), whereas the fate of oil compounds deposited in surface layers (0-5
      cm) mainly was affected by removal processes induced by wave actions and other
      bioturbating infauna such as Nereis diversicolor, Corophium volutator and
      Hydrobia spp. present in the experimental plots.

PMID- 21186047
TI  - Gene expression analysis of HUVEC in response to TF-binding.
AB  - INTRODUCTION: Tissue factor (TF), the cofactor for factor VII/VIIa (FVII/FVIIa)
      and initiator of the extrinsic pathway, is transiently expressed on intravascular
      cells under control of cytokines and growth factors. In addition, endothelial
      cells express a binding site for external TF. In the present study, we
      investigated gene expression of endothelial cells derived from human umbilical
      veins (HUVEC) in response to TF-binding to identify differentially expressed
      genes. MATERIALS AND METHODS: HUVEC were treated with recombinant relipidated TF
      (Innovin) versus nontreated cells, as well as TF/FVIIa versus FVIIa alone. TF
      binding was measured by ELISA. Gene expression profiles were examined using HG
      U133 plus 2.0 arrays (Affymetrix). RESULTS: Gene expression analysis of HUVEC
      showed 148 up-regulated and 29 down-regulated genes 4h after TF binding. Notably,
      the genes, which were significantly up- and down-regulated, either by TF alone or
      by the complex of TF/FVIIa, exhibited a complete overlap, indicating that
      activation of endothelial cells after binding of external added TF does not
      depend on FVIIa as has been demonstrated for TF-expressing cells. TF-mediated
      regulation of gene expression of several genes, involved in regulation of
      apoptosis, cell adhesion, cell motility, and angiogenesis, was confirmed by qPCR.
      Furthermore, in case of SELE, TGFB2, TNFAIP3, TNFSF4, TNFSF18, TAGLN, CXCL1,
      PCF11 antibodies directed to TF clearly inhibited TF-mediated regulation of gene
      expression. CONCLUSIONS: The results demonstrate that interaction of TF with
      HUVEC via a binding site, independent from FVIIa, may result in regulation of a
      variety of genes involved in arteriosclerosis, cancer, and cardiovascular
      diseases.

PMID- 21186048
TI  - A rapid, automated VWF ristocetin cofactor activity assay improves reliability in
      the diagnosis of Von Willebrand disease.
AB  - INTRODUCTION: The effective diagnosis and monitoring of Von Willebrand Disease
      (VWD) requires an accurate assessment of ristocetin co-factor activity (VWF:RCo).
      Current methodologies include automated platelet aggregometry and manual visual
      agglutination both of which are laborious to perform and notoriously subject to a
      high degree of inter and intra assay variation. METHODS AND MATERIALS: We have
      evaluated an automated VWF:RCo assay (BC Von Willebrand Reagent, Siemens,
      Marberg, Germany) for use on the Sysmex CS2100i analyser (Milton Keynes, UK) and
      retrospectively compared the results with an in-house manual visual agglutination
      assay and VWF antigen (Siemens) in normal subjects and in 53 patients with
      various types of VWD and 23 patients following VWF therapeutic treatment.
      RESULTS: The intra and interassay CV was improved with the automated assay (2.3%
      and 3.8% respectively) compared to 7% with the manual VWF:RCo assay. Good
      correlation was found between the two assays (r=0.91) in 53 patients with VWD.
      The mean manual VWF:RCo was 0.25IU/ml and mean automated VWF:RCo was 0.27IU/ml. A
      comparable increase in VWF:RCo following treatment, mostly with Desmopressin, was
      found in 13 patients with type 1 VWD (mean 3.9 fold increase with manual VWF:RCo
      and 3.1 fold with the automated VWF:RCo). In 13 patients with type 2 or 3 VWD
      following treatment mostly with concentrate , a higher increase was found with
      the automated VWF:RCo assay than the manual assay (mean 11.9 fold manually and
      mean 20.3 automated). CONCLUSION: The automated VWF:RCo assay shows enhanced
      precision and analysis time in this difficult and time consuming laboratory test
      and its introduction should greatly improve the reliability of VWF testing.

PMID- 21186049
TI  - Comparison of the effect of homocysteine in the reduced form, its thiolactone and
      protein homocysteinylation on hemostatic properties of plasma.
AB  - Mechanisms involved in the relationship between hyperhomocysteinemia and
      hemostatic process are still unclear. In the literature there are few papers
      describing studies on the effects of homocysteine (Hcys) on proteins that
      participate in blood coagulation and fibrinolysis in human. The aim of our study
      was to establish and compare the influence of a reduced form of Hcys (at final
      doses of 0.01 - 1 mM) and the most reactive form of Hcys - its cyclic thioester,
      homocysteine thiolactone (HTL, 0.1 - 1 MUM) on the clot formation (using whole
      human plasma and purified fibrinogen) and the fibrin lysis. Moreover, the aim of
      our study was to explain the effect of plasma protein modifications (S- and N
      homocysteinylation) on selected parameters of hemostasis. We observed that HTL,
      like its precursor, a reduced form of Hcys stimulated polymerization of
      fibrinogen, but this process was not dose-dependent. In the presence of HTL (at
      the lowest tested concentration - 0.1MUM) the increase was about 55%. Our present
      results also demonstrated that Hcys in the reduced form (0.01 - 1 mM) and HTL at
      lower doses than Hcys (0.1 - 1 MUM) reduced the fibrin lysis in whole human
      plasma. Our results reported that HTL, like the reduced form of Hcys (at
      concentrations corresponding to concentrations in plasma during
      hyperhomocysteinemia) induced modifications of hemostatic plasma proteins, and
      the consequence of these modifications may be alteration in protein structure
      associated with changes of hemostatic functions.

PMID- 21186050
TI  - The clock gene Per2 is required for normal platelet formation and function.
AB  - INTRODUCTION: Apoptotic cell death is a highly regulated genetic program, which
      has been observed in mature megakaryocytes fragmenting into platelets. The clock
      gene Per2, a key component of core clock oscillator, was involved in affecting
      both cell cycle control and apoptosis. Thus, loss of Per2 function may be
      considered potential influence of platelet formation and function. METHODS: Per2
      null mice and C57BL/6 mice were used in the study. Bleeding time, platelet count,
      megakaryocyte count, megakaryocyte ploidy, megakaryocyte apoptosis, rate of
      proplatelet formation, clot retraction, platelet aggregation and secretion were
      performed to evaluate thrombopoiesis and hemostasis. Quantitative RT-PCR was
      employed to analyze genes expression in liver, bone marrow and enriched
      megakaryocytes. RESULTS: The Per2-null mice had nearly 50% platelet counts in
      peripheral blood. Per2-null platelets were compromised in their ability to
      aggregate and secretion, consistent with a marked reduction in the number of
      dense and a-granules. Megakaryocytes from Per2-null mice showed no significant
      variation in number but increased in ploidy. Ultrastructural examination of Per2
      null megakaryocytes revealed many vacuoles in demarcation membranes and reduction
      in platelet granules. Megakaryocytes from Per2-null bone marrow decreased the
      rate of proplatelet formation and impaired apoptosis. Per2-null mice showed
      increased both in Tpo in livers and its receptors C-mpl in bone marrow, and the
      megakaryocytes from these mice decreased P53 expression, consequently increased
      Bcl-xl and Bcl-2 level. CONCLUSIONS: The clock gene Per2 modulating the apoptosis
      of megakaryocytes was required for platelet formation and function.

PMID- 21186051
TI  - Urethral steinstrasse causing acute urinary retention.
AB  - Multiple urethral calculi-forming steinstrasse in the urethra leading to acute
      urinary retention is a rare event in pediatric urolithiasis. We report a child
      with urethral steinstrasse that cleared spontaneously with attempted urethral
      catheterization.

PMID- 21186052
TI  - Recombinant spider silk particles as drug delivery vehicles.
AB  - Spider silk has been in the focus of research mainly due to the superior
      mechanical characteristics of silk fibers. However, it has been previously shown
      that spider silk proteins can also adopt other morphologies such as
      submicroparticles. This study examines the applicability of such particles as
      drug carriers. Particle characterization revealed that particles made of the
      engineered spider silk protein eADF4(C16) are colloidally stable in solution.
      Here, it is shown that small molecules with positive net-charge can diffuse into
      the negatively charged spider silk protein matrix driven by electrostatic
      interactions. The loading efficiencies correlate with the distribution
      coefficient (logD) of small molecules of weak alkaline nature. Interestingly,
      constant release rates can be realized for a period of two weeks at physiological
      conditions in vitro, with accelerated release rates within acidic environments.
      Enzymatic degradation studies of eADF4(C16) particles indicated that the silk
      proteins degrade slowly and the particles decrease in size. Along with their all
      aqueous and easy preparation, drug loaded eADF4(C16) particles provide a high
      potential for diverse applications in which controlled release from biodegradable
      carriers is desired.

PMID- 21186053
TI  - Ultrasensitive electrochemical immunoassay for BRCA1 using BMIM.BF4-coated SBA-15
      as labels and functionalized graphene as enhancer.
AB  - BRCAl is an anti-oncogene in women, who are genetically predisposed to breast and
      ovary cancer. The detection of BRCA1 can offer an opportunity to characterize the
      function of genetic features in breast and ovarian cancer and to screen breast or
      ovarian cancer patients. In this study, we designed a new label and fabricated a
      novel sandwich-type electrochemical immunoassay for the ultrasensitive detection
      of BRCAl. Horseradish peroxidase (HRP) was entrapped in the pores of amino-group
      functionalized SBA-15 and the secondary antibody (Ab2) combined with SBA-15 by
      covalent bond. Ionic liquid (IL) was added into the mixed solution of SBA
      15/HRP/Ab2 and application of IL increased the electrochemical activity of HRP
      and promoted electron transport. The synergistic effect between IL, SBA-15, Ab2
      and HRP could retain the bioactivity of HRP and Ab2. The sensitivity of the
      sandwich-type immunosensor using SBA-15/HRP/Ab2/BMIM.BF4 as labels for BRCA1
      detection was much higher than that using either SBA-15/HRP/Ab2 or SBA-15/Ab2 as
      labels. Under optimal conditions, the electrochemical immunoassay exhibited a
      wide working range from 0.01 to 15 ng/mL with a detection limit of 4.86 pg/mL
      BRCA1. The precision, reproducibility, and stability of the immunoassay were
      acceptable.

PMID- 21186054
TI  - DNA assembly and re-assembly activated by cationic comb-type copolymer.
AB  - Guanine-rich oligonucleotides, such as TG(4)T and TG(5)T, assemble into a
      tetramolecular quadruplexes with layers of G-quartets stabilized by coordination
      to monovalent cations. Association rates of the quadruplexes are extremely slow,
      likely owing to electrostatic repulsion among the four strands. We have shown
      that comb-type copolymers with a polycation backbone and abundant hydrophilic
      graft chains form water-soluble polyelectrolyte complexes with DNA and promote
      DNA hybridization. Here, we report the effect of cationic comb-type copolymers on
      the kinetics of tetramolecular quadruplex formation. The copolymer significantly
      increased the association rate of tetramolecular quadruplexes without altering
      kinetic effects of metal cations in quadruplex formation. Dissociation rates of
      the quadruplexes were also accelerated by the copolymer suggesting that the
      copolymer has chaperone-like activity that reduces the energy barriers associated
      with dissociation and re-assembly of base pairs. This hypothesis was further
      supported by the observation that the copolymer activated the strand exchange
      reaction between the quadruplex and a constituting single-stranded.

PMID- 21186055
TI  - Oral pharmacokinetics of the anti-HIV efavirenz encapsulated within polymeric
      micelles.
AB  - Aiming to improve the pediatric pharmacotherapy of the human immunodeficiency
      virus (HIV) infection, our group has recently developed a concentrated
      formulation of the first-line antiretroviral efavirenz by means of encapsulation
      within polymeric micelles. The aqueous solubility of the drug was increased more
      than 8400 times (up to 34mg/mL) and preliminary preclinical data suggested the
      significantly greater oral bioavailability with respect to an extemporaneous
      suspension and an oleous solution (similar to the only "commercially available"
      pediatric formulation). As the preamble to a bioequivalence trial to evaluate the
      micellar system in adult healthy volunteers, the present work investigated the
      effect of parameters such as dose per body weight and drug concentration on the
      oral pharmacokinetics of the drug. The non-linear pharmacokinetics of the drug
      was confirmed for all the formulations. Despite the drug concentration and dose,
      micelles consistently resulted in significantly greater absorption rates, PK
      parameters increasing up to 3-fold. For example, C(max) values increased from
      687, 1789 and 2657ng/mL for the oily system to 1145, 2856 and 7056ng/mL for the
      micellar one, for EFV doses between 20 and 80mg/kg. Data clearly showed that the
      smaller the micellar size, the higher the bioavailability attained. The effect of
      micellar size was also assessed. In addition, a comparison between in vitro
      dissolution rates of EFV for the different micelles and AUC values suggested that
      micelles releasing faster in vitro lead to a less pronounced absorption in vivo.
      These findings would suggest the involvement of additional absorption mechanisms.

PMID- 21186057
TI  - A model for biodegradation of composite materials made of polyesters and
      tricalcium phosphates.
AB  - A saturation behaviour has been observed when incorporating tricalcium phosphate
      (TCP) in various polyesters to control the degradation rate. This paper presents
      an understanding of this behaviour using a mathematical model. The coupled
      process of hydrolysis reaction of the ester bonds, acid dissociation of the
      carboxylic end groups, dissolution of the calcium phosphates and buffering
      reactions by the dissolved phosphate ions is modelled together using a set of
      differential equations. Two non-dimensional groups of the material and chemical
      parameters are identified which control the degradation rate of the composites.
      An effectiveness map is established to show the conditions under which
      incorporating TCP into polyesters is effective, saturated or ineffective.
      Comparisons are made between the model predictions and existing experimental data
      in the literature. The map provides a useful tool to guide the design of
      polyester/TCP composites for tissue engineering and orthopaedic fixation
      applications.

PMID- 21186056
TI  - Delivery of basic fibroblast growth factor with a pH-responsive, injectable
      hydrogel to improve angiogenesis in infarcted myocardium.
AB  - A pH- and temperature-responsive, injectable hydrogel has been designed to take
      advantage of the acidic microenvironment of ischemic myocardium. This system can
      improve therapeutic angiogenesis methods by providing spatio-temporal control of
      angiogenic growth factor delivery. The pH- and temperature-responsive random
      copolymer, poly(N-isopropylacrylamide-co-propylacrylic acid-co-butyl acrylate)
      (p[NIPAAm-co-PAA-co-BA]), was synthesized by reversible addition fragmentation
      chain transfer polymerization. This polymer was a liquid at pH 7.4 and 37 
      degrees C but formed a physical gel at pH 6.8 and 37  degrees C. Retention of
      biotinylated basic fibroblast growth factor (bFGF) between 0 and 7 days after
      injection into infarcted rat myocardium was 10-fold higher with hydrogel delivery
      versus saline. Following 28 days of treatment in vivo, capillary and arteriolar
      densities were increased 30-40% by polymer + bFGF treatment versus saline + bFGF
      or polymer-only controls. Treatment with polymer + bFGF for 28 days resulted in a
      2-fold improvement in relative blood flow to the infarct region versus day 0,
      whereas saline + bFGF or polymer-only had no effect. Fractional shortening
      determined by echocardiography was significantly higher following treatment with
      polymer + bFGF (30 +/- 1.4%) versus saline (25 +/- 1.2%) and polymer alone (25 +/
      1.8%). By responding to local changes in pH- and temperature in an animal model
      of ischemia, this hydrogel system provided sustained, local delivery of bFGF,
      improved angiogenesis, and achieved therapeutic effects in regional blood flow
      and cardiac function.

PMID- 21186058
TI  - The role of PEG architecture and molecular weight in the gene transfection
      performance of PEGylated poly(dimethylaminoethyl methacrylate) based cationic
      polymers.
AB  - In this study, we report the synthesis of well-defined model PEGylated
      poly(dimethylaminoethyl methacrylate) based cationic polymers composed of
      different PEG architecture with controlled PEG and nitrogen content via
      reversible addition-fragmentation chain transfer (RAFT) polymerization, and study
      the effects of PEG architecture and polymer molecular weight on gene delivery and
      cytotoxicity. Investigation of the physico-chemical interactions of these model
      cationic polymers with DNA demonstrated that all these polymers effectively
      complexed with DNA, and PEG topology did not significantly affect the abilities
      of the polymers to complex and release DNA. However the size and zeta potential
      of the complexes were found to be influenced by PEG architecture. The polymers
      with the block-like configurations formed nanosized DNA complexes. In contrast,
      considerably higher molecular weight was necessary for the copolymer with the
      statistical configuration of short PEG chains to form such a small complex. Cell
      line-dependent influence of PEG architecture on cellular uptake, gene expression
      efficiency and cell viability of the polymer-DNA complexes was observed. The
      diblock copolymer-DNA complexes induced higher gene expression than the brush
      like block copolymer-DNA complexes, and the statistical copolymer-DNA complexes
      mediated much lower gene expression than the block-like copolymers-DNA complexes.
      Increasing the molecular weight of statistical polymer to some extent improved
      gene expression efficiency. The statistical copolymer was less cytotoxic as
      compared to the block-like copolymers. These findings provide important insights
      into the effect of PEGylation nature on gene expression, which will be useful for
      the design of PEGylated gene delivery polymers.

PMID- 21186059
TI  - The synergistic effect of hierarchical assemblies of siRNA and chemotherapeutic
      drugs co-delivered into hepatic cancer cells.
AB  - Diblock copolymers (PEI-PCL) of poly(epsilon-caprolactone) (PCL) and linear
      poly(ethylene imine) (PEI) were synthesized and assembled to biodegradable nano
      carriers for co-delivery of BCL-2 siRNA and doxorubicin (DOX). Folic acid as a
      tumor-targeting ligand was conjugated to the polyanion, poly(ethylene glycol)
      block-poly(glutamic acid) (FA-PEG-PGA). Driven by the electrostatic interaction,
      FA-PEG-PGA was coated onto the surface of the cationic PEI-PCL nanoparticles pre
      loaded with siRNA and DOX, potentiating a ligand-directed delivery to human
      hepatic cancer cells Bel-7402. At certain N/P and C/N ratios (N/P: PEI-PCL
      nitrogen to siRNA phosphate; C/N: FA-PEG-PGA carboxyl to PEI-PCL amine), the
      nanoparticles exhibited not only high transfection efficiency but also ideally
      controlled release of drug. Compared to non-specific delivery, the folate
      targeted delivery of BCL-2 siRNA resulted in more significant gene suppression at
      both the BCL-2 mRNA and protein expression levels, inducing cancer cell apoptosis
      and improving the therapeutic efficacy of the co-administered DOX. Herein we
      demonstrated that co-loading siRNA and small molecular drug in a multifunctional
      hierarchical nano-assembly enabled simultaneously delivering siRNA and drug into
      the same cancer cells, yielding synergistic effect of RNA interference and
      chemotherapy in cancer.

PMID- 21186060
TI  - Two Litopenaeus vannamei HMGB proteins interact with transcription factors LvSTAT
      and LvDorsal to activate the promoter of white spot syndrome virus immediate
      early gene ie1.
AB  - White spot syndrome virus (WSSV) has caused great economic damage to shrimp
      aquaculture. Previous studies have shown that WSSV successfully usurps the
      immunity system of the host for its own gene regulation. To investigate the role
      of shrimp high mobility group box (HMGB) proteins in WSSV gene regulation, two
      Litopenaeus vannamei HMGB genes, LvHMGBa and LvHMGBb, were isolated by rapid
      amplification of cDNA ends (RACE). Recombinant LvHMGBa/b proteins were present in
      the nucleus of transfected Drosophila Schneider 2 (S2) cells. Luciferase reporter
      assays revealed that LvHMGBa/b upregulated the WSSV immediate-early (IE) gene
      (ie1) in a NF-kappaB and STAT binding site-dependent manner. GST pull-down assays
      demonstrated that LvHMGBa/b interacted with L. vannamei Dorsal (LvDorsal) and L.
      vannamei STAT (LvSTAT), respectively. LvHMGBa was highly expressed in
      hepatopancreas while HMGBb was highly expressed in stomach, intestine, heart,
      antennal gland, and epidermis. Moreover, an immune challenge assay demonstrated
      that the expression of LvHMGBa/b was upregulated by WSSV infection and that both
      mRNAs reached peak values at 24 h post-infection. To our knowledge, this is the
      first report that invertebrate HMGB proteins participates in viral gene
      regulation.

PMID- 21186061
TI  - Emerging effortful control in toddlerhood: the role of infant
      orienting/regulation, maternal effortful control, and maternal time spent in
      caregiving activities.
AB  - Latent growth modeling (LGM) was used to examine the contribution of changes in
      infant orienting/regulation (O/R) to the emergence of toddler effortful control
      (EC), the contributions of maternal EC to the development of infant O/R and the
      emergence of toddler EC, the influence of maternal time spent in caregiving
      activities on toddler EC and the slope of infant O/R, and the contribution of
      maternal EC to subsequent maternal time spent in caregiving activities. Mothers
      from 158 families completed a self-report measure of EC when their infants were 4
      months of age, a measure of infant O/R when their infants were 4, 6, 8, 10, and
      12 months of age, and a measure of toddler EC when their children reached 18
      months of age. Information concerning maternal time spent in various interactive
      caregiving activities was collected when infants were 6 months old. Results
      indicated higher maternal EC predicted interindividual differences in the
      intercept (i.e., higher intercepts), but not slope, of infant O/R and that higher
      maternal EC, higher infant O/R intercept, and higher infant O/R slope contributed
      to higher toddler EC. Furthermore, higher maternal EC predicted greater maternal
      time spent in interactive caregiving activities with their infants and greater
      maternal time in interactive caregiving with infants also contributed to higher
      toddler EC after controlling for maternal EC. These findings contribute to the
      understanding of the influence of maternal EC, directly and through caregiving,
      on toddler EC. Additional implications as they are related to early developing
      regulatory aspects of temperament are discussed.

PMID- 21186062
TI  - A pilot double-blind sham-controlled trial of repetitive transcranial magnetic
      stimulation for patients with refractory schizophrenia treated with clozapine.
AB  - Schizophrenia is a complex and heterogeneous psychiatric disorder. Auditory
      verbal hallucinations occur in 50-70% of patients with schizophrenia and are
      associated with significant distress, decreased quality of life and impaired
      social functioning. This study aimed to investigate the effects of active
      compared with sham 1-Hz repetitive transcranial magnetic stimulation (rTMS)
      applied to the left temporal-parietal cortex in patients with schizophrenia
      treated with clozapine. Symptom dimensions that were evaluated included general
      psychopathology, severity of auditory hallucinations, quality of life and
      functionality. Seventeen right-handed patients with refractory schizophrenia
      experiencing auditory verbal hallucinations and treated with clozapine were
      randomly allocated to receive either active rTMS or sham stimulation. A total of
      384 min of rTMS was administered over 20 days using a double-masked, sham
      controlled, parallel design. There was a significant reduction in Brief
      Psychiatric Rating Scale (BPRS) scores in the active group compared with the sham
      group. There was no significant difference between active and sham rTMS on
      Quality of Life Scale (QLS), Auditory Hallucinations Rating Scale (AHRS),
      Clinical Global Impressions (CGI) and functional assessment staging (FAST)
      scores. Compared with sham stimulation, active rTMS of the left temporoparietal
      cortex in clozapine-treated patients showed a positive effect on general
      psychopathology. However, there was no effect on refractory auditory
      hallucinations. Further studies with larger sample sizes are needed to confirm
      these findings.

PMID- 21186064
TI  - Vitamin D has a direct immunomodulatory effect on CD8+ T cells of patients with
      early multiple sclerosis and healthy control subjects.
AB  - Little is known on a putative effect of vitamin D on CD8+ T cells. Yet, these
      cells are involved in the immmunopathogenesis of MS. We assessed the cytokine
      profile of EBV-specific CD8+ T cells of 10 early MS patients and 10 healthy
      control subjects with or without 1,25(OH)(2)D(3) and found that, with
      1,25(OH)(2)D(3), these cells secreted less IFN-gamma and TNF-alpha and more IL-5
      and TGF-beta. CD4+ T cell depletion or even culture with CD8+ T cells only did
      not abolish the immunomodulatory effect of 1,25(OH)(2)D(3) on CD8+ T cells,
      suggesting that 1,25(OH)(2)D(3) can act directly on CD8+ T cells.

PMID- 21186063
TI  - Age-associated alterations in sympathetic noradrenergic innervation of primary
      and secondary lymphoid organs in female Fischer 344 rats.
AB  - Normal aging processes, as well as, psychological stress affect the immune
      system; each can act alone, or interact with each other, to cause dysregulation
      of immune function substantially altering physical and mental health. The
      sympathetic nervous system (SNS), a major mediator of stress effects on immune
      function, is significantly affected by normal aging process, and stress can
      affect aging of the SNS. Previously, we have shown age-associated changes in
      sympathetic noradrenergic (NA) innervation of lymphoid organs in male rodents
      that affect immune regulation. The purpose of this study was to investigate
      sympathetic innervation of lymphoid organs and associated alterations in immune
      responses in young and aging female Fischer 344 (F344) rats. Histofluorescence
      and immunocytochemistry for NA innervation, and neurochemistry for norepinephrine
      (NE) levels were performed in the thymus, spleen, and mesenteric lymph nodes
      (MLN) isolated from 3-month-old young (normal estrous cycle), 8- to 9-month-old
      (onset of irregular estrous cycling), and 24-25 month, and 30-31 month female
      F344 rats (acyclic) at diestrus based on vaginal smears. Age-related alterations
      in natural killer (NK) cell activity, interleukin-2 (IL-2) and interferon-gamma
      (IFN-gamma) production, T and B lymphocyte proliferation were examined in
      splenocytes. Sympathetic NA innervation and NE levels increased with aging in the
      thymus, declined in spleen and MLN, and was accompanied by significant reductions
      in NK cell activity, IL-2 and IFN-gamma production, and T and B cell
      proliferation in old female rats. In 8-9 mo rats, NE levels in the hilar region
      of the spleen and IFN-gamma production were unaltered, while NE levels in the end
      region of the spleen and IL-2 production were reduced. Collectively, these
      results suggest that aging is characterized by significant alterations in
      sympathetic NA innervation in the thymus, spleen, and MLN associated with
      immunosuppression, and that there is a marked shift in NA activity and immune
      reactivity occurring during middle-aged female rats.

PMID- 21186065
TI  - Rendering hospital budgets volume based and open ended to reduce waiting lists:
      does it work?
AB  - In the past decades fixed budgets for hospitals were replaced by reimbursement
      based on outputs in several countries in order to bring down waiting lists. This
      was also the case in the Netherlands where fixed global budgets were replaced by
      budgets that are to a large extent volume based and in practice open-ended. The
      objective of this study was to examine the effectiveness of this Dutch policy
      measure, which was implemented in 2001. We carried out a statistical analysis and
      interpretation of trends in Dutch hospital admission rates. We observed a
      significant turn in the development of in-patient admission rates after the
      abolition of budget caps in 2001: decreasing admission rates turned into an
      internationally exceptional increase of more than 3% per year. Day care
      admissions had already been rising explosively for two decades, but the pace
      increased after 2001. The increase in the number of admissions includes a broad
      range of patient categories that were not in the first place associated with long
      waiting times. The growth was attributable for a large part to admissions for
      observation of the patient and the evaluation of symptoms, not resulting in a
      definite medical diagnosis. We considered several factors, other than the
      availability of more resources, to explain the growth: the ageing of the
      population, making up for waiting list arrears, ditto for "under consumption" of
      unplanned care and, as to the growth of day care, substitution for inpatient
      care. However, these factors were all found to fall short as an explanation.
      Although waiting times have dropped since the change in the budget system, they
      continue to be long for several procedures. Our study indicates that making
      available more resources to admit patients, or otherwise an increase in hospital
      activity, do not in itself lead to equilibrium between demand and supply because
      the volume and composition of demand are partly induced by supply. We conclude
      that abolishing budget caps to solve waiting list problems is not efficient.
      Instead of a generic measure, a more focused approach is necessary. We suggest
      ingredients for such an approach.

PMID- 21186066
TI  - Behaviour and fate of nine recycled water trace organics during managed aquifer
      recharge in an aerobic aquifer.
AB  - The fate of nine trace organic compounds was evaluated during a 12month large
      scale laboratory column experiment. The columns were packed with aquifer sediment
      and evaluated under natural aerobic and artificial anaerobic geochemical
      conditions, to assess the potential for natural attenuation of these compounds
      during aquifer passage associated with managed aquifer recharge (MAR). The nine
      trace organic compounds were bisphenol A (BPA), 17beta-estradiol (E2), 17alpha
      ethynylestradiol (EE2), N-nitrosodimethylamine (NDMA), N-nitrosomorpholine
      (NMOR), carbamazepine, oxazepam, iohexol and iodipamide. In the low organic
      carbon content Spearwood sediment, all trace organics were non-retarded with
      retardation coefficients between 1.0 and 1.2, indicating that these compounds
      would travel at near groundwater velocities within the aquifer. The natural
      aerobic geochemical conditions provided a suitable environment for the rapid
      degradation for BPA, E2, iohexol (half life <1day). Lag-times for the start of
      degradation of these compounds ranged from <15 to 30days. While iodipamide was
      persistent under aerobic conditions, artificial reductive geochemical conditions
      promoted via the addition of ethanol, resulted in rapid degradation (half life
      <1days). Pharmaceuticals (carbamazepine and oxazepam) and disinfection by
      products (NDMA and NMOR) did not degrade under either aerobic or anaerobic
      aquifer geochemical conditions (half life >50days). Field-based validation
      experiments with carbamazepine and oxazepam also showed no degradation. If
      persistent trace organics are present in recycled waters at concentrations in
      excess of their intended use, natural attenuation during aquifer passage alone
      may not result in extracted water meeting regulatory requirements. Additional pre
      treatment of the recycled water would therefore be required.

PMID- 21186067
TI  - Synthesis and biological activity of novel inhibitors of topoisomerase I: 2-aryl
      substituted 2-bis-1H-benzimidazoles.
AB  - Inhibitors of topoisomerase I constitute a novel family of antitumor agents. The
      class of benzimidazole derivatives contains compounds possessing affinity to DNA.
      For example, fluorescent stains Hoechst 33342 and Hoechst 33258 interact with DNA
      as ligand and produce nonspecific inhibition of the catalytic activity of many
      enzymes involved in DNA synthesis, including DNA topoisomerase and DNA helicase.
      Several 2-aryl-5-substituted-2,5-bisbenzimidazole derivatives were synthesized
      and ability of these derivatives to induce DNA cleavage in the presence of
      topoisomerase I was evaluated in vitro. These analogs were also assayed for their
      cytotoxicity against U87, MCF7 and HeLa human tumor cells. All the four compounds
      showed a potent growth inhibitory effect on all the cell lines, with IC50 in the
      MUM range.

PMID- 21186068
TI  - Developing spatially stratified N(2)O emission factors for Europe.
AB  - We investigate the possibility to replace the - so-called - Tier 1 IPCC approach
      to estimate soil N(2)O emissions with stratified emissions factors that take into
      account both N-input and the spatial variability of the environmental conditions
      within the countries of the European Union, using the DNDC-Europe model. Spatial
      variability in model simulations is high and corresponds to the variability
      reported in literature for field data. Our results indicate that (a) much of the
      observed variability in N(2)O fluxes reflects the response of soils to external
      conditions, (b) it is likely that national inventories tend to overestimate the
      uncertainties in their estimated direct N(2)O emissions from arable soils; (c) on
      average over Europe, the fertilizer-induced emissions (FIE) coincide with the
      IPCC factors, but they display large spatial variations. Therefore, at scales of
      individual countries or smaller, a stratified approach considering fertilizer
      type, soil characteristics and climatic parameters is preferable.

PMID- 21186069
TI  - Ecotoxicity of nanosized TiO2. Review of in vivo data.
AB  - This report presents an exhaustive literature review of data on the effect of
      nanoparticulate TiO(2) on algae, higher plants, aquatic and terrestrial
      invertebrates and freshwater fish. The aim, to identify the biologically
      important characteristics of the nanoparticles that have most biological
      significance, was unsuccessful, no discernable correlation between primary
      particle size and toxic effect being apparent. Secondary particle size and
      particle surface area may be relevant to biological potential of nanoparticles,
      but insufficient confirmatory data exist. The nanotoxicity data from thirteen
      studies fail to reveal the characteristics actually responsible for their
      biological reactivity because reported nanotoxicity studies rarely carry
      information on the physicochemical characteristics of the nanoparticles tested. A
      number of practical measures are suggested which should support the generation of
      reliable QSAR models and so overcome this data inadequacy.

PMID- 21186070
TI  - Ni adsorption and Ni-Al LDH precipitation in a sandy aquifer: an experimental and
      mechanistic modeling study.
AB  - Mining activities and industries have created nickel (Ni) contaminations in many
      parts of the world. The objective of this study is to increase our understanding
      of Ni adsorption and Nickel-Aluminium Layered Double Hydroxide (Ni-Al LDH)
      precipitation to reduce Ni mobility in a sandy soil aquifer. At pH >= 7.2 both
      adsorption and Ni-Al LDH precipitation occurred. In batch experiments with the
      sandy soil up to 70% of oxalate-extractable Al was taken up in LDH formation
      during 56 days. In a long term column experiment 99% of influent Ni was retained
      at pH 7.5 due to Ni adsorption (~ 34%) and Ni-Al LDH precipitation (~ 66%) based
      on mechanistic reactive transport modeling. The subsequent leaching at pH 6.5
      could be largely attributed to desorption. Our results show that even in sandy
      aquifers with relatively low Al content, Ni-Al LDH precipitation is a promising
      mechanism to immobilize Ni.

PMID- 21186071
TI  - Urinary total globotriaosylceramide and isoforms to identify women with Fabry
      disease: a diagnostic test study.
AB  - BACKGROUND: Fabry disease is a treatable X-linked lysosomal storage disorder
      caused by alterations in the structural gene (GLA) of alpha-galactosidase A
      (AGAL), manifesting with cardiovascular and/or kidney disease and decreased life
      span. Although males as well as females can be affected, females cannot be
      identified using AGAL activity. We evaluated urinary total globotriaosylceramide
      (Gb3) and single N-acyl isoforms for the detection of Fabry disease in female
      patients with and without chronic kidney disease (CKD). STUDY DESIGN: Diagnostic
      accuracy study. SETTING & PARTICIPANTS: 28 untreated women with Fabry disease and
      335 female outpatients without Fabry disease with (n = 213) and without CKD (n =
      122). INDEX TEST: Assessment of urinary Gb3 using electrospray ionization tandem
      mass spectrometry, including 6 N-acyl isoforms, total Gb3 related to urinary
      creatinine, and ratios of Gb3-24 to Gb3-18 and Gb3-24 to urinary AGAL. REFERENCE
      TEST: Fabry disease, diagnosed by identification of known pathogenic GLA
      mutations in patients or their male relatives. RESULTS: 6 parameters (ratio of
      Gb3-24 to urinary AGAL activity; Gb3-24; ratio of Gb3-24 to Gb3-18; Gb3-22; Gb3
      16; and total Gb3) were highly informative for the diagnosis of Fabry disease
      independent of the presence or absence of CKD (area under the receiver operating
      characteristic curve, 0.876-0.927; all P < 0.001). LIMITATIONS: Because of low
      signal-to-noise ratios, 15.8% of samples had to be excluded. CONCLUSION: Total
      urinary Gb3 and Gb3 isoforms can be used for the diagnosis of Fabry disease in
      women.

PMID- 21186072
TI  - Trends in parathyroidectomy rates in US hemodialysis patients from 1992 to 2007.
AB  - BACKGROUND: Parathyroidectomy rates in hemodialysis patients increased from 1992
      to 2002, when medication choices to manage secondary hyperparathyroidism
      expanded. STUDY DESIGN: Retrospective follow-up registry study. SETTING &
      PARTICIPANTS: We evaluated annual cohorts of point-prevalent US hemodialysis
      patients with Medicare as primary payer for 1992-2007 (n = 1,063,258 for 1992
      1999; 757,207 for 2000-2003; 902,119 for 2004-2007). PREDICTOR: Comorbid
      conditions, vitamin D use, previous kidney transplant, and parathyroid hormone
      testing were assessed in the previous year. Available bone and mineral disorder
      treatment patterns were evaluated. OUTCOMES: We examined incidence rate trends
      and patient characteristics through 2007 to estimate the association between
      parathyroidectomy and patient factors. Follow-up was from January 1 of each study
      year to the earliest in the same year of parathyroidectomy, death, or December
      31. MEASUREMENTS: We used chi(2) analysis to compare patient characteristics in 3
      time frames. Unadjusted and adjusted parathyroidectomy rates were calculated. Cox
      regression was used to test the association of parathyroidectomy and covariates.
      RESULTS: Adjusted parathyroidectomy rates increased from 1998 (7.0/1,000 patient
      years; 1,045 events), peaked in 2002 (12.8/1,000 patient-years; 2,229 events),
      decreased through 2005 (5.4/1,000 patient-years; 1,078 events), and increased in
      2006 (8.6/1,000 patient-years; 1,743 events) and 2007 (8.8/1,000 patient-years;
      1,832 events). Vitamin D use, virtually undetectable in 1991, subsequently
      steadily increased; >80% of patients received vitamin D in 2006. LIMITATIONS: The
      study was not designed to provide causal explanations for observed changes; oral
      medication use trend data were limited to one large dialysis provider and may not
      reflect use patterns in all dialysis facilities; because Medicare is not the
      primary payer for all US hemodialysis patients, results do not describe the
      entire US hemodialysis population; parathyroid hormone values are lacking in the
      database. CONCLUSIONS: Adjusted parathyroidectomy rates varied substantially from
      1992 through 2007. Rates were highest in 1994 and 2002 and lowest in 1998 and
      2005, likely influenced by changing medication use patterns and guideline
      publication.

PMID- 21186073
TI  - The role of tight junctions in paracellular ion transport in the renal tubule:
      lessons learned from a rare inherited tubular disorder.
AB  - Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an
      autosomal recessive renal tubular disorder that typically presents with
      disturbances in magnesium and calcium homeostasis, recurrent urinary tract
      infections, and polyuria and/or polydipsia. Patients with FHHNC have high risk of
      the development of chronic kidney disease and end-stage renal disease in early
      adolescence. Multiple distinct mutations in the CLDN16 gene, which encodes a
      tight junction protein, have been found responsible for this disorder. In
      addition, mutations in another member of the claudin family, CLDN19, were
      identified in a subset of patients with FHHNC with visual impairment. The
      claudins belong to the family of tight junction proteins that define the
      intercellular space between adjacent endo- and epithelial cells. Claudins are
      especially important for the regulation of paracellular ion permeability. We
      describe a Brazilian family with 2 affected siblings presenting with the typical
      FHHNC phenotype with ocular anomalies. The clinical diagnosis of FHHNC was
      confirmed using mutational analysis of the CLDN19 gene, which showed 2 compound
      heterozygous mutations. In the context of the case vignette, we summarize the
      clinical presentation, diagnostic criteria, and therapeutic options for patients
      with FHHNC. We also review recent advances in understanding the
      electrophysiologic function of claudin-16 and -19 in the thick ascending limb of
      the loop of Henle and implications for ion homeostasis in the human body.

PMID- 21186074
TI  - Association of plasma aldosterone with cardiovascular mortality in patients with
      low estimated GFR: the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study.
AB  - BACKGROUND: We have previously shown that plasma aldosterone levels within the
      physiologic reference range predicted increased all-cause and cardiovascular
      disease (CVD) mortality in patients referred for coronary angiography. Decreased
      kidney function is associated with a marked increase in CVD mortality that is not
      explained fully by known cardiovascular risk factors. We hypothesized that level
      of kidney function might modify the association between plasma aldosterone level
      and CVD mortality. STUDY DESIGN: Prospective cohort study. SETTING &
      PARTICIPANTS: 3,153 patients (mean age, 62.7 +/- 10.6 years; 30.1% women) free of
      primary kidney disease at baseline were referred for coronary angiography in a
      tertiary-care center in Southwest Germany between 1997 and 2000. PREDICTORS:
      Plasma aldosterone level, determined using radioimmunoassay. Tertiles of
      estimated glomerular filtration rate (eGFR) based on creatinine and cystatin C
      levels. OUTCOMES & MEASUREMENTS: CVD mortality and sudden cardiac death events at
      7.75 years. RESULTS: At baseline, median plasma aldosterone concentration was
      79.0 (25th-75th percentile, 48.0-124.0) pg/mL. Mean eGFR was 83.8 +/- 20.1 (SD)
      mL/min/1.73 m(2), and mean eGFRs in tertiles 1-3 were 61.9 +/- 13.0, 84.7 +/-
      4.4, and 104.7 +/- 10.3 mL/min/1.73 m(2), respectively. After a median follow-up
      of 7.75 years, 454 (14.4%) patients died of cardiovascular causes and 179 (5.7%)
      died suddenly. Multivariate Cox proportional hazard analyses showed increased
      risks of CVD mortality (HR per 50-pg/mL increment in plasma aldosterone
      concentration, 1.08; 95% CI, 1.03-1.12; P = 0.001) and sudden cardiac death (HR,
      1.11; 95% CI, 1.06-1.15; P < 0.001). In tertiles 1-3 of eGFR, adjusted HRs per 50
      pg/mL increment in plasma aldosterone concentration for CVD mortality were 1.10
      (95% CI, 1.05-1.14; P < 0.001), 1.00 (95% CI, 0.83-1.16; P = 0.8), and 0.97 (95%
      CI, 0.75-1.26; P = 0.8), respectively (product term for interaction, P = 0.001),
      and for sudden cardiac death were 1.13 (95% CI, 1.08-1.17; P < 0.001), 0.99 (95%
      CI, 0.75-1.29; P = 0.9), and 0.90 (95% CI, 0.60-1.34; P = 0.5), respectively
      (product term for interaction, P < 0.001). LIMITATIONS: No urinary analysis was
      performed to assess dietary salt intake and proteinuria. CONCLUSIONS: Our
      findings suggest that the association of higher plasma aldosterone concentration
      with overall CVD mortality and sudden cardiac death is stronger for patients with
      lower kidney function.

PMID- 21186075
TI  - Long-term clinical outcomes following drug-eluting or bare-metal stent placement
      in patients with severely reduced GFR: Results of the Massachusetts Data Analysis
      Center (Mass-DAC) State Registry.
AB  - BACKGROUND: Patients with chronic kidney disease have been under-represented in
      randomized trials of drug-eluting stents relative to bare-metal stents and are at
      high risk of mortality. STUDY DESIGN: Cohort study with propensity score
      matching. SETTINGS & PARTICIPANTS: All adults with chronic kidney disease and
      severely decreased glomerular filtration rate (GFR; serum creatinine >2.0 mg/dL
      or dialysis dependence) undergoing percutaneous coronary intervention with stent
      placement between April 1, 2003, and September 30, 2005, at all acute-care
      nonfederal hospitals in Massachusetts. PREDICTOR: Patients were classified as
      drug-eluting stent-treated if all stents were drug eluting and bare-metal stent
      treated if all stents were bare metal. Patients treated with both types of stents
      were excluded from the primary analysis. OUTCOMES & MEASUREMENTS: 2-year crude
      mortality risk differences (drug-eluting - bare-metal stents) were determined
      from vital statistics records, and risk-adjusted mortality, myocardial infraction
      (MI), and revascularization differences were estimated using propensity score
      matching of patients with severely reduced GFR based on clinical and procedural
      information collected at the index admission. RESULTS: 1,749 patients with
      severely reduced GFR (24% dialysis dependent) were treated with drug-eluting (n =
      1,256) or bare-metal stents (n = 493) during the study. Overall 2-year mortality
      was 32.8% (unadjusted drug-eluting stent vs bare-metal stent; 30.1% vs 39.8%; P <
      0.001). After propensity score matching 431 patients with a drug-eluting stent to
      431 patients with a bare-metal stent, 2-year risk-adjusted mortality, MI, and
      target-vessel revascularization rates were 39.4% versus 37.4% (risk difference,
      2.1%; 95% CI, -4.3 to 8.5; P = 0.5), 16.0% versus 19.0% (risk difference, -3.0%;
      95% CI, -8.2 to 2.1; P = 0.3), and 13.0% versus 17.6% (risk difference, -4.6%;
      95% CI, -9.5 to 0.3; P = 0.06). LIMITATIONS: Observational design, ascertainment
      of serum creatinine level >2.0 mg/dL and dialysis dependence from case report
      forms. CONCLUSIONS: In patients with severely decreased GFR, treatment with drug
      eluting stents was associated with a modest decrease in target-vessel
      revascularization not reaching statistical significance and was not associated
      with a difference in risk-adjusted rates of mortality or MI at 2 years compared
      with bare-metal stents.

PMID- 21186076
TI  - Talking about colds and flu: the lay diagnosis of two common illnesses among
      older British people.
AB  - This paper reports on a study of the ways in which 54 older people in South Wales
      (UK) talk about the symptoms and causes of cold and influenza (flu). The study
      was designed to understand why older people might reject or accept the offer of
      seasonal flu vaccine, and in the course of the interviews respondents were also
      asked to express their views about the nature and causes of the two key
      illnesses. The latter are among the most common infections in human beings. In
      terms of the biomedical paradigm the common cold is caused by numerous
      respiratory viruses, whilst flu is caused by the influenza virus. Medical
      diagnosis is usually made on clinical grounds without laboratory confirmation.
      Symptoms of flu include sudden onset of fever and cough, and colds are
      characterized by sneezing, sore throat, and runny nose, but in practice the
      symptoms often overlap. In this study we examine the degree by which the views of
      lay people with respect to both diagnosis and epidemiology diverge with that
      which is evident in biomedical discourse. Our results indicate that whilst most
      of the identified symptoms are common to lay and professional people, the former
      integrate symptoms into a markedly different observational frame from the latter.
      And as far as causation is concerned it is clear that lay people emphasize the
      role of 'resistance' and 'immunity' at least as much as 'infection' in accounting
      for the onset of colds and flu. The data are analyzed using novel methods that
      focus on the co-occurrence of concepts and are displayed as semantic networks. As
      well as reporting on its findings the authors draw out some implications of the
      study for social scientific and policy discussions concerning lay diagnosis, lay
      expertise and the concept of an expert patient.

PMID- 21186078
TI  - Dendritic cells engineered to express GITRL enhance therapeutic immunity in
      murine Lewis lung carcinoma.
AB  - Glucocorticoid-induced tumor necrosis factor receptor and its ligand (GITRL) are
      critically involved in the regulation of immune response. In this study, we aimed
      to generate bone marrow-derived dendritic cells (BMDCs) transfected with
      recombinant adenovirus expressing GITRL (pAd-GITRL-BMDCs) and explore their
      therapeutic efficacy in murine Lewis lung carcinoma. In vitro, pAd-GITRL-BMDCs
      greatly enhanced effector T cells proliferation but markedly abrogate the
      suppression of Treg cells. Moreover, vaccination with pAd-GITRL-BMDCs
      significantly retarded tumor growth, which was accompanied with increased IFN
      gamma-producing CD8+ T cells and markedly decreased Treg cells in vivo. These
      findings suggest GITRL could enhance the immune stimulation of DC and might
      facilitate the potential development of DCs-based anti-tumor therapies.

PMID- 21186077
TI  - A prospective, randomised EORTC intergroup phase 3 study comparing the oncologic
      outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage
      renal cell carcinoma.
AB  - BACKGROUND: Nephron-sparing surgery (NSS) can safely be performed with slightly
      higher complication rates than radical nephrectomy (RN), but proof of oncologic
      effectiveness is lacking. OBJECTIVE: To compare overall survival (OS) and time to
      progression. DESIGN, SETTING, AND PARTICIPANTS: From March 1992 to January 2003,
      when the study was prematurely closed because of poor accrual, 541 patients with
      small (<=5 cm), solitary, T1-T2 N0 M0 (Union Internationale Contre le Cancer
      [UICC] 1978) tumours suspicious for renal cell carcinoma (RCC) and a normal
      contralateral kidney were randomised to NSS or RN in European Organisation for
      Research and Treatment of Cancer Genito-Urinary Group (EORTC-GU) noninferiority
      phase 3 trial 30904. INTERVENTION: Patients were randomised to NSS (n=268) or RN
      (n=273) together with limited lymph node dissection (LND). MEASUREMENTS: Time to
      event end points was compared with log-rank test results. RESULTS AND
      LIMITATIONS: Median follow-up was 9.3 yr. The intention-to-treat (ITT) analysis
      showed 10-yr OS rates of 81.1% for RN and 75.7% for NSS. With a hazard ratio (HR)
      of 1.50 (95% confidence interval [CI], 1.03-2.16), the test for noninferiority is
      not significant (p=0.77), and test for superiority is significant (p=0.03). In
      RCC patients and clinically and pathologically eligible patients, the difference
      is less pronounced (HR=1.43 and HR=1.34, respectively), and the superiority test
      is no longer significant (p=0.07 and p=0.17, respectively). Only 12 of 117 deaths
      were the result of renal cancer (four RN and eight NSS). Twenty-one patients
      progressed (9 after RN and 12 after NSS). Quality of life and renal function
      outcomes have not been addressed. CONCLUSIONS: Both methods provide excellent
      oncologic results. In the ITT population, NSS seems to be significantly less
      effective than RN in terms of OS. However, in the targeted population of RCC
      patients, the trend in favour of RN is no longer significant. The small number of
      progressions and deaths from renal cancer cannot explain any possible OS
      differences between treatment types.

PMID- 21186079
TI  - miR-185 targets RhoA and Cdc42 expression and inhibits the proliferation
      potential of human colorectal cells.
AB  - Increasing evidence in the past few years has shown that miRNAs could serve
      functionally as "oncogenes" or "tumor suppressor genes" and regulate multiple
      cellular processes relevant to carcinogenesis and cancer progression. Both RhoA
      and Cdc42, two members of the Rho GTPase family, are found to be upregulated in
      several types of human tumors including colorectal cancer, and have been
      implicated in cancer initiation and progression. In the present studies, we found
      that miR-185 expression greatly inhibited the proliferation potential of Hela
      cells. An examination of the predicted targets of miR-185 revealed RhoA and Cdc42
      among the putative targets that are crucial for cell proliferation. A genomic
      sequence analysis indicated that nt 1844-1852 of the RhoA 3'UTR and nt 1382-1396
      of the cdc42 3'UTR encode for miR-185 target matching sequences and they are
      highly conserved across different species. Using a luciferase-reporter assay, we
      show that miR-185 expression significantly suppressed the RhoA and Cdc42 3'UTR
      activities, and the inhibitory effect was lost when the putative target sites for
      miR-185 were mutated. Consistent with these results, ectopic expression of miR
      185 reduced protein levels of RhoA and Cdc42 in cells, indicating miR-185
      functionally regulates RhoA and Cdc42 abundance. Similar to the effects of
      knocking down RhoA and/or Cdc42 expression, miR-185 effectively inhibited
      proliferation, induced G1 cell cycle arrest and apoptosis, and blocked invasion
      of colorectal cancer cells. Thus, miR-185 is a negative regulator of RhoA and
      Cdc42 and their cellular activities, and could inhibit proliferation and invasion
      of colorectal cancer cells.

PMID- 21186080
TI  - Removal of As(III) and As(V) from water by copper oxide incorporated mesoporous
      alumina.
AB  - In the present manuscript a new adsorbent namely copper oxide incorporated
      mesoporous alumina (COIMA) for removal of arsenic from water is reported. The
      COIMA was prepared by treating mesoporous alumina with copper sulphate solution
      followed by calcination at 450 degrees C in the presence of air. Various
      adsorption isotherm and kinetic parameters were computed using batch adsorption
      studies to determine the adsorption capacity for As(III) and As(V) and to
      understand the mechanism of adsorption. It was observed that incorporation of
      copper oxide improves the adsorption capacity of unmodified alumina from 0.92 to
      2.16 mg g(-1) for As(III) and from 0.84 to 2.02 mg g(-1) for As(V). The results
      revealed that the adsorption follows Langmuir isotherm and pseudo-second-order
      kinetic models for both As(III) and As(V). The material is capable of
      simultaneously removing As(III) and As(V) with removal efficiencies of more than
      95% for both As(III) and As(V). Assessment of the water quality before and after
      treatment with COIMA also confirmed that the there is no leaching of copper and
      other parameters were also within permissible limits of Indian drinking water
      standard indicating that the COIMA can be used for treatment of arsenic
      contaminated drinking water.

PMID- 21186081
TI  - Hip and knee arthroplasty: failures among the successes.

PMID- 21186082
TI  - Psychosocial correlates of adolescent marijuana use: variations by status of
      marijuana use.
AB  - INTRODUCTION: This study examined the associations between psychosocial factors
      and status of marijuana use: former experimentation, current occasional, and
      current frequent use. METHODS: Data were collected from a nationally
      representative sample of U.S. tenth-graders who participated in the 2005/6 Health
      Behavior in School-aged Children Study (n=1465). Multinomial regressions, run
      separately by gender, examined the association of risk and protective factors
      from the individual (life satisfaction; academic achievement; aggression,
      bullying) and contextual (mothers and fathers' knowledge of adolescents'
      activities, school climate) domains with status of marijuana use (former
      experimentation, current occasional use, current frequent use). RESULTS: Former
      experimental and current marijuana uses were negatively associated with
      protective factors such as academic achievement, mothers' and fathers' knowledge
      of adolescents' activities, and life satisfaction, but not with positive school
      climate. Former experimental and current marijuana uses were positively
      associated with aggression and bullying perpetration. Most associations varied by
      gender and status of marijuana use. In adjusted analyses, aggression emerged as
      the sole risk factor and fathers' knowledge as the sole protective factor
      associated with most statuses of marijuana use, across gender. CONCLUSION:
      Fathers may be particularly important in preventing adolescent marijuana use, and
      interventions promoting fathers' knowledge of adolescents' activities are
      warranted.

PMID- 21186083
TI  - Viability and proliferation of pluripotential cells delivered to tendon repair
      sites using bioactive sutures--an in vitro study.
AB  - PURPOSE: We evaluated the fate of pluripotential stem cells adherent to a suture
      carrier after being passed through tendon tissue in vitro. METHODS: FiberWire
      suture segments were coated with poly-L-lysine (PLL) and a 2 * 10(6) C3H10T1/2 (a
      mouse embryo pluripotential cell line) cell suspension. The sutures were
      incubated for 7 days, passed through two 1-cm segments of acellularized rabbit
      Achilles tendons and tied (horizontal mattress). The repairs were frozen and
      sectioned (6 MUm). The sections were stained with 4',6-diamidino-2-phenylindole
      and a live/dead viability/cytotoxicity (calcein/ethidium homodimer) kit and
      examined with fluorescent microscopy to evaluate cell presence and viability.
      Alamar Blue was used in parallel to assess metabolic activity. RESULTS: PLL
      coated sutures showed a 3-fold increase in fluorescence when compared with the
      phosphate-buffered saline-coated controls. At day 3, fluorescence was 2.2 times
      greater. At day 5, a 2-fold increase was found, and at day 8 there was no
      significant difference in values. Furthermore, after delivery of the cells into
      tendon, fluorescence readings for the samples (n = 19) showed 9450 compared with
      the positive control at 21,218. At 96 hours the mean was 27,609 compared with
      34,850 for the positive control. The difference in fluorescence means at 48 hours
      and 96 hours were significant (p < .001). Live-dead and DAPI staining confirmed
      the presence of live cells at the tendon repair site. CONCLUSIONS: Sutures seeded
      with pluripotential embryonic cells deliver cells to a tendon repair site. The
      cells deposited at the repair site survive the trauma of passage and remain
      metabolically active, as seen in staining and metabolic assay studies. Use of
      bioactive sutures leads to repopulation of the acellular zone surrounding sutures
      within the tendon.

PMID- 21186084
TI  - The herpetic whitlow.

PMID- 21186085
TI  - Malignant transformation of multiple enchondromas in the hand: case report.
AB  - Enchondromatosis can transform into chondrosarcoma, but this event is rare in the
      hand. We present the case of a patient with chondrosarcomas of the ring and
      little fingers. The chondrosarcomas had a long progression of 60 years and the
      patient presented with large tumors and a severely deformed appearance.

PMID- 21186086
TI  - Epidemiology of suspected wrist joint infection versus inflammation.
AB  - PURPOSE: To determine the cumulative prevalence of septic arthritis presenting to
      the emergency department of an academic medical center and evaluate the use of
      clinical data to diagnose infection versus inflammation. METHODS: We conducted a
      records review of a single institution with 80,000 annual emergency room visits.
      We included a consecutive series of patients with suspected wrist infection from
      January 1, 2007, to December 31, 2008. Adults complaining of atraumatic wrist
      pain with either erythema or swelling on physical examination or a final
      diagnosis of septic arthritis, gout, pseudogout, cellulitis, wrist
      hematoma/edema, or wrist arthritic flare were suspected to have infection. We
      collected data using a standardized data abstraction form. RESULTS: We reviewed
      804 patient records. A total of 104 patients meeting inclusion criteria for
      suspected wrist joint infection during the 2-year study period were included.
      Mean age was 62.5 years (SD, 20.2 y); 63 were men. There were 12 patients with a
      history of gout, 4 with a history of pseudogout, and 19 with a history of
      diabetes. Wrist arthrocentesis was performed in 31 patients, and 11 underwent
      surgical treatment. There were 16 patients with a final diagnosis of gout, 11
      with pseudogout, 43 with cellulitis, 13 with upper extremity hematoma/edema, and
      15 with wrist arthritic flare. The cumulative prevalence of septic arthritis was
      5%. CONCLUSIONS: In this series of emergency department patients with suspected
      wrist joint infection, gout, pseudogout, and cellulitis were the most common
      etiologies. The cumulative incidence of septic wrist arthritis was low.

PMID- 21186087
TI  - Reconstructive options of burn injuries to the hand and upper extremity.

PMID- 21186088
TI  - Arthrodesis as a salvage for failed proximal interphalangeal joint arthroplasty.
AB  - PURPOSE: To review the rate of fusion, complications, and subjective outcome
      measures of proximal interphalangeal joint arthrodesis after failed implant
      arthroplasty. METHODS: We conducted a retrospective review identifying patients
      from 1990 to 2009 who underwent proximal interphalangeal joint arthrodesis for
      implant arthroplasty failure. All types of implants were included. We reviewed
      clinical notes and radiographs identifying patient history, implant type,
      revisions before arthrodesis, method of arthrodesis, rate of union, time to
      union, and complications. We used the Michigan Hand Outcomes Questionnaire to
      assess patients' function and perceived clinical outcome. RESULTS: A total of 13
      joints in 8 patients (6 female, 2 male) identified with an average clinical
      follow-up of 6.5 years (range, 1.0-12.3 y) were available for study. The average
      time from joint replacement to salvage for all implant types was 9.3 years
      (range, 1.6-32.2 y). Eight of the 13 fingers achieved union. The average time to
      union was 5.8 months (range, 1-11 mo). Eight of 13 fingers underwent removal of K
      wires, tension band, or both. Excluding hardware-related problems, there were 4
      additional complications in 4 patients. CONCLUSIONS: Salvage of failed proximal
      interphalangeal joint arthroplasty remains a challenging clinical problem.
      Although achieving solid fusion with arthrodesis is not completely reliable or
      without complication, patients' subjective and functional outcomes demonstrate
      fair to good results. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 21186089
TI  - Role of vascularized bone grafts in the treatment of scaphoid nonunions
      associated with proximal pole avascular necrosis and carpal collapse.

PMID- 21186090
TI  - [Antenatal screening for HIV: knowledge, attitudes, beliefs and practices of
      pregnant women. Analysis of current practices and the impact of setting up an
      informative brochure].
AB  - OBJECTIVES: To assess the impact of an information leaflet on the behavior and
      knowledge of pregnant women about the risks of HIV infection during pregnancy.
      PATIENTS AND METHODS: Comparative prospective study conducted in two phases from
      March 1 to September 30, 2007 on patients presenting for the first time in
      antenatal care at the Maternity Hospital of Tours (n=539). During the first
      phase, only a self-questionnaire was given during the second an informative
      brochure has been attached to the questionnaire. RESULTS: Currently 25.1% of
      pregnant women have not made a test during their pregnancy. This rate decreases
      to 12.9% when the test is routinely offered. It falls to 8.2% with the
      introduction of an informative brochure. The test was imposed in 28.7% of
      patients. Some risks of transmission of HIV, including those specific to
      pregnancy, are undervalued. A negative test before the pregnancy is the main
      reason for refusal of antenatal screening. A high level of education was the only
      risk factor identified for refusal. They are better informed as shown by the
      higher rate of correct answers about the risks of HIV transmission and antenatal
      screening. We hypothesize that the women who pursued graduate studies evaluate
      the risk of infection before accepting or refusing the test. CONCLUSION: The
      study shows that the distribution of an informative brochure on advanced prenatal
      screening, increased the number of women performing the test and improved their
      knowledge about risks of transmission, especially from mother to the child.

PMID- 21186091
TI  - Delayed colo-anal anastomosis is an alternative to prophylactic diverting stoma
      after total mesorectal excision for middle and low rectal carcinomas.
AB  - BACKGROUND: After total mesorectal excision (TME), a low colorectal or colo-anal
      anastomosis is usually performed. A prophylactic covering stoma is often used,
      especially for patients receiving neoadjuvant chemo-radiotherapy. However,
      morbidity is high, mainly due to anastomotic leakage. METHODS: From May 2000 to
      October 2008, patients with middle or low rectal cancer who underwent a trans
      anal pull-through procedure after TME were prospectively recorded. No covering
      stoma was performed in these patients. However, they all underwent a delayed colo
      anal anastomosis (DCA), which was performed 6 days following the TME, on average.
      Both the surgical technique and follow-up were standardised. Patients with T3, T4
      and/or N+ cancers were given preoperative radiotherapy. A retrospective analysis
      was done to assess post-operative mortality, morbidity, and oncologic and
      functional results. RESULTS: One hundred consecutive patients with rectal tumours
      at a median distance of 5 cm from the anal verge underwent DCA after TME. The 5
      year overall and disease-free survival rates were 81% and 66%, respectively. The
      post-operative mortality rate was 3% and the overall post-operative morbidity
      rate was 36%, with only 3 anastomotic leakages. After two years, 73% of the
      patients had good functional outcomes. CONCLUSION: The trans-anal pull-through
      procedure after TME, followed by DCA seems to be a safe and efficient sphincter
      preserving procedure to treat patients with middle or low rectal cancer while
      avoiding a prophylactic, diverting stoma.

PMID- 21186092
TI  - Pathomechanisms and complications related to patient positioning and anesthesia
      during shoulder arthroscopy.
AB  - The lateral decubitus and beach-chair positions each offer unique benefits to the
      shoulder surgeon with respect to visualization, efficiency, and ease during
      arthroscopic shoulder procedures. The purpose of this article was to
      comprehensively review the reports and studies documenting independent and
      dependent complications related to patient positioning and anesthesia during
      arthroscopic shoulder surgery. The lateral decubitus position has been associated
      with the potential for peripheral neurapraxia, brachial plexopathy, direct nerve
      injury, and airway compromise. The beach-chair position has been associated with
      cervical neurapraxia, pneumothorax, and the potential for end-organ hypoperfusion
      injuries (when deliberate hypotension is used). Potentially concerning are
      hypotensive bradycardic events, which may be relatively common in association
      with the use of epinephrine-containing interscalene anesthetics in beach chair
      positioned patients. Irrigant complications (fluid spread, ventricular
      tachycardia) are avoidable risks not unique to either specific position. Although
      minor transient anesthetic- and position-related complications (neurapraxia,
      hypotension) may occur in as many 10% to 30% of patients, major complications
      such as end-organ damage or permanent impairments are exceedingly rare.
      Regardless of position, complications are almost uniformly avoidable if surgeon
      and anesthetist exercise care and prudent attention to position and anesthetic
      choices. The purpose of this article is to review the potential for position- and
      anesthesia-related complications and acquaint the shoulder surgeon with the
      proposed pathophysiologic mechanisms that can lead to them.

PMID- 21186093
TI  - [Haemodynamic monitoring or output cardiac monitoring? Reply].

PMID- 21186094
TI  - [Neuromonitoring and prognosis after severe brain injury: beyond cerebral
      perfusion pressure alone].

PMID- 21186095
TI  - Anti-protozoal activity of diamine derivatives.
AB  - Ten N-monoalkylated diamines were synthesized and evaluated for in vitro
      activities against Trichomonas vaginalis and Giardia lamblia. Several compounds
      displayed a good inhibition of parasite growth, with MIC less or equal to
      20MUg/mL. N-hexadecil-1,4-butanediamine was found to be the most active compound
      in vitro against T. vaginalis with MIC of 2.5MUg/mL, twice more active in
      comparison to the reference drug metronidazole (MTZ). Seven of the studied
      compounds showed a better anti-G. lamblia activity than MTZ.

PMID- 21186096
TI  - Identification of voice disorders using long-time features and support vector
      machine with different feature reduction methods.
AB  - Identification of voice disorders has a fundamental role in our life nowadays.
      Therefore, many of these diseases must be diagnosed at early stages of occurrence
      before they lead to a critical condition. Acoustic analysis can be used to
      identify voice disorders as a complementary technique with other traditional
      invasive methods, such as laryngoscopy. In this article, we followed an extensive
      study in the diagnosis of voice disorders using the statistical pattern
      recognition techniques. Finally, we proposed a combined scheme of feature
      reduction methods followed by pattern recognition methods to classify voice
      disorders. Six classifiers are used to evaluate feature vectors obtained by
      principal component analysis or linear discriminant analysis (LDA) as feature
      reduction methods. Furthermore, individual, forward, backward, and branch-and
      bound methods are examined as feature selection methods. The performance of each
      combined scheme is evaluated in terms of the accuracy, sensitivity, specificity,
      and area under the receiver operating characteristic curve (AUC). The
      experimental results denote that LDA along with support vector machine (SVM) has
      the best performance, with a recognition rate of 94.26% and AUC of 97.94%.
      Additionally, this structure has the lowest complexity in comparison with other
      architectures. Among feature selection methods, individual feature selection
      followed by SVM classifier shows the best recognition rate of 91.55% and AUC of
      95.80%.

PMID- 21186097
TI  - Pre-morbid Conduct Disorder symptoms are associated with cannabis use among
      individuals with a first episode of psychosis.
AB  - BACKGROUND: Early cannabis use has consistently been associated with an increased
      risk for the later development of psychosis. Studies suggest that Conduct
      Disorder (CD) is more common amongst young people who later go on to develop
      psychosis. CD has been associated with greater and earlier cannabis use in
      general population samples. Based on this evidence, we hypothesised that among
      patients experiencing their first episode of psychosis, the presence of CD
      symptoms prior to age 15 would be associated with cannabis use. METHOD: 102
      patients experiencing a first episode of psychosis were interviewed to assess CD
      symptoms prior to age 15 and use of cannabis and other substances. RESULTS: The
      number of CD symptoms was significantly associated with lifetime cannabis use
      (odds ratio=5.41 (1.76-16.57), p=0.03) and with first use of cannabis before age
      14 (odds ratio=1.46 (1.12-1.92), p=0.006), after controlling for
      stimulant/hallucinogen use and level of education. CONCLUSIONS: Among patients
      experiencing a first episode of psychosis, CD symptoms were significantly
      associated with use of cannabis and with use by age 14. Among individuals
      vulnerable for psychosis, CD symptoms may independently increase the likelihood
      of cannabis use which in turn increases the risk of psychosis.

PMID- 21186098
TI  - Visuo-spatial cognition in schizophrenia: confirmation of a preference for local
      information processing.
AB  - During visuo-spatial cognitive tasks, patients with schizophrenia show a
      preference for local (detailed) rather than global (holistic) information
      processing. The efficiency of such information processing is influenced by task
      difficulty. We tested whether patients' preference for local processing would
      persist if task demands favored global or local processing. Twenty-four
      stabilized patients with schizophrenia (SZ) and 25 healthy, matched controls (C)
      were tested in a mental mirroring task. Task difficulty was manipulated while
      stimulus surface structures were maintained unchanged. Information processing was
      assessed by recording eye movements. SZ were slower than C in the easiest
      condition but they made more errors than C in the more difficult conditions.
      Further, SZ did not adapt their average fixation duration to task demands
      resulting in longer fixation duration in the easiest condition and shorter
      fixation duration in the most difficult condition compared to C. These findings
      suggest that patients employ local information processing even when it is
      maladaptive for task demands. That is, patients do not adapt their fixation
      duration to task demands implicating (i) a preference for scanning local stimuli
      features and (ii) information processing inflexibility. These features need to be
      taken into account when evaluating visuo-spatial cognitive performance in
      schizophrenia.

PMID- 21186099
TI  - Biological response of hydrogels embedding gold nanoparticles.
AB  - A nanocomposite hydrogel based on natural polysaccharides and gold nanoparticles
      (ACnAu) has been prepared and its biological effects were tested in vitro with
      both bacteria and eukaryotic cells. Antimicrobial tests showed that AC-nAu gels
      are effective in killing both gram+ (Staphylococcus aureus) and gram-
      (Pseudomonas aeruginosa) bacteria. LDH assays pointed at a toxic effect towards
      eukaryotic cell-lines (HepG2 and MG63), in contrast with the case of silver-based
      hydrogels; cytofluorimetry studies demonstrated an apoptosis-related mechanism
      induced by increase of ROS intracellular level which leads to cell death after 24
      h of direct contact with AC-nAu gels. In vivo biocompatibility has been evaluated
      in a rat model, investigating the peri-implant soft tissue reaction after 1 month
      of implantation. The results show that silver-containing samples induced a
      fibrotic capsule of the same average thickness of the control sample (devoid of
      nanoparticles) (~50 MUm), while in the case of gold containing materials the
      fibrotic capsule was thicker (~100 MUm), confirming a higher biocompatibility for
      silver-based samples than for gold-based ones.

PMID- 21186100
TI  - Health literacy and the provision of information to women with breast cancer.
AB  - AIMS: Health literacy and functional health literacy are important for patients
      with cancer, as key information regarding treatment complications and clinical
      trials is often imparted using written educational material. This study measured
      the health literacy and functional health literacy levels in a population of
      women with breast cancer and compared these with the level of written information
      provided. MATERIALS AND METHODS: A cross-sectional survey of women with stage I
      III breast cancer attending an outpatient clinic was conducted. Health literacy
      levels were assessed using the Rapid Estimate of Adult Literacy in Medicine
      (REALM) score and functional health literacy was assessed using three validated
      screening questions. Patient education materials were assessed using the Simple
      Measure of Gobbledygook (SMOG) and Flesch Reading Ease (FRE) systems. RESULTS:
      One hundred and twenty-seven women were recruited. For patients, the mean REALM
      score was 64.3 (>=US 9th grade/reading age 14 years). The mean SMOG score of
      patient education materials was 80.5 (reading age 17 years). The mean FRE score
      of patient education materials was 55.7 (reading age 15-17 years). All patient
      information sheets assessed were written at >=8th grade (reading age 13 years)
      and as a result up to 9% of patients would be unable to read them. Nineteen per
      cent of the population had inadequate functional health literacy. CONCLUSIONS:
      Health literacy levels were high in the population studied. However, the reading
      level of written patient information was also high, meaning that up to 9% of
      patients would be unable to read the information provided. Functional health
      literacy levels were lower, with 19% of patients having inadequate ability. This
      means that although most patients are able to read the information sheets
      provided, there is a larger proportion that would be unable to understand and act
      upon this information. Patient education materials should be written at an
      appropriate level and different modalities of communication should be used to
      ensure adequate comprehension.

PMID- 21186101
TI  - Metabolic syndrome and coronary heart disease among Spanish male workers: a case
      control study of MESYAS.
AB  - BACKGROUND AND AIMS: In Spain, the incidence of coronary heart disease is below
      that expected based on the burden of classic cardiovascular risk factors present
      in the population. Whether the risk associated with metabolic syndrome is lower
      in Spain deserves to be investigated. This study evaluates the association of
      incident clinical coronary heart disease with metabolic syndrome and each of its
      individual defining components in a sample of Spanish working males. METHODS AND
      RESULTS: Among the workers of a factory (MESYAS registry), 208 incident cases of
      coronary heart disease (between 1981 and 2005) were age-matched with 2080 healthy
      workers visited in 2004-2005. Metabolic syndrome was characterized using modified
      criteria of the joint consensus definition (2009). Metabolic syndrome was
      strongly associated with coronary heart disease (OR = 4.03; 95% CI: 2.98, 5.45)
      and the risk seemed to be fully explained by metabolic syndrome components (OR =
      0.84, p = 0.54 after adjustment). Odds ratios for the independent effects of the
      diagnostic criteria were: hypertriglyceridemia (OR = 3.39, p < 0.001),
      hyperglycemia (OR = 2.70, p < 0.001), low HDL cholesterol (OR = 2.35, p < 0.001),
      hypertension (OR = 1.49, p = 0.016) and overweight (OR = 1.07, p = 0.678). Young
      workers showed a higher risk associated with metabolic syndrome. CONCLUSION: The
      risk associated with metabolic syndrome is fully explained by its components
      considered independently. The risk of coronary heart disease in a Spanish male
      working population is considerably increased among those with metabolic syndrome,
      by a factor similar to that described for other countries. Public health measures
      to prevent a rise in the prevalence of metabolic syndrome are advisable to
      minimize cardiovascular disease rate in Spain.

PMID- 21186102
TI  - Role of oxidized low density lipoproteins and free fatty acids in the
      pathogenesis of glomerulopathy and tubulointerstitial lesions in type 2 diabetes.
AB  - Oxidized lipids initiate and modulate the inflammatory cellular events in the
      arterial wall and the formation of macrophage foam cells. CD36 mediates the
      cellular uptake of ox-LDL through its recognition of specific truncated fatty
      acid moieties and oxidized phosphatidylcholine. Evidence has been reported that
      chemokine CXCL16, rather than CD36, is the main scavenger receptor in human
      podocytes mediating the uptake of ox-LDL. Ox-LDL induces loss of nephrin
      expression from cultured podocytes. It has been recently shown that nephrin once
      phosphorilated associates with PI3K and stimulates the Akt dependent signaling.
      This pathway plays a critical role in nephrin-actin-dependent cytoskeleton
      activation and remodeling, in the control of protein trafficking and in podocyte
      survival. An enhanced FFA uptake by podocytes is mediated by increased C36
      scavenger receptor expression, together with a decrease of betaoxidation and in
      turn intracellular lipid accumulation. Accumulated FFA that is trapped into the
      mitochondrial matrix leads to mitochondrial ROS production, lipid peroxidation
      and mitochondrial damage and dysfunction. A disturbed transport and oxidation of
      FFA, paralleled by an impaired antioxidant response, damages podocyte structure
      and leads to glomerulopathy in early stages of nephrosis. Increased triglyceride
      synthesis and ox-and glycated LDL uptake by mesangial cells may also contribute
      to determine diabetic glomerulopathy. Oxidative processes are pivotal events in
      injury to renal tubular and epithelial cells exposed to ox-LDL. Notably CXCL16
      are the main receptors for the uptake of ox-LDL in podocytes, whereas CD36 plays
      this role in tubular renal cells. In overt type 2 diabetes Ox-LDL and FFA damage
      podocyte function, SD-podocyte structure and tubulointerstitial tissue, at least
      partially, through different pathogenetic mechanisms. Further studies are needed
      to investigate the role of Ox-LDL and FFA on renal complications in obese,
      insulin resistant patients before the development of diabetes. The aim of the
      present review is to briefly elucidate the patterns of systemic lipid metabolism
      and the individual effects of lipotoxicity at glomerular and tubular level in the
      kidney of overt type 2 diabetic patients. These findings better elucidate our
      knowledge of diabetic glomerulopathy, beside and along with previous findings, in
      vivo and in vitro, on ox-LDL and FFA effects in mesangial cells.

PMID- 21186103
TI  - Characteristics of diet patterns in metabolically obese, normal weight adults
      (Korean National Health and Nutrition Examination Survey III, 2005).
AB  - BACKGROUND AND AIMS: Metabolically obese normal weight (MONW) subjects are a
      subgroup of individuals who have a normal weight and body mass index (BMI), but
      exhibit obesity-related abnormalities. The objective of this study was to analyze
      the prevalence of metabolic syndrome (MetS) and characteristics of diet patterns
      in MONW Koreans. METHODS AND RESULTS: We analyzed the data of 3050 adults > 20
      years of age with a normal BMI (18.5~24.9 kg/m(2)) obtained from the Korea
      National Health and Nutrition Examination Survey III. Anthropometric measurements
      and information on health behaviors were obtained. The diagnostic criteria for
      MetS were defined by the International Diabetes Federation consensus. Dietary
      intake was assessed by the 24-h recall method. The weighted prevalence of MONW
      was 14.3%. The risk of MONW correlated inversely with the frequency of snacking
      and positively with the type of snack, particularly those with high
      carbohydrates. A high carbohydrate diet (>=73.9% of energy intake) compared to a
      low carbohydrate diet (<59.9% of energy intake) was positively associated with
      the risk of MONW (OR = 2.54; 95% CI: 1.41, 4.56), whereas a high protein diet
      (>=17.1% of energy intake) compared to a low protein diet (<12.2% of energy
      intake) reduced the risk of MONW (OR = 0.60; 95% CI: 0.39, 0.92) in females, but
      not in males. CONCLUSIONS: This study suggests that a reduced intake of
      carbohydrates and carbohydrate snacks were associated with a lower prevalence of
      MONW in females.

PMID- 21186104
TI  - Global cardiovascular risk management in different Italian regions: an analysis
      of the Evaluation of Final Feasible Effect of Control Training and Ultra
      Sensitisation (EFFECTUS) educational program.
AB  - BACKGROUND AND AIM: The Final Evaluation Feasible Effect of Ultra Control
      Training and Sensitization (EFFECTUS) is an educational program, aimed at
      improving global CV risk stratification and management in Italy. The present
      study evaluates differences on clinical approach to global CV risk among
      physicians involved in the EFFECTUS program and stratified in three geographical
      macro-areas (North, Center, South) of our Country. METHODS AND RESULTS:
      Physicians were asked to submit data already available in their medical records,
      covering the first 10 adult outpatients, consecutively seen in the month of May
      2006. Overall, 1.078 physicians (27% females, aged 50 +/- 7 years) collected data
      of 9.904 outpatients (46.5% females, aged 67 +/- 9 years), among which 3.219
      (32.5%) were residents in Northern, 3.652 (36.9%) in Central and 3.033 (30.6%) in
      Southern Italy. A significantly higher prevalence of major CV risk factors,
      including obesity, physical inactivity, hypertension and diabetes, was recorded
      in Southern than in other areas. Accordingly, Southern physicians more frequently
      prescribed antihypertensive, glucose and lipid lowering agents than other
      physicians, who paid significantly more attention to life-style changes in their
      clinical practice. CONCLUSIONS: This analysis of the EFFECTUS study demonstrates
      a high prevalence of CV risk factors in Italy, particularly in Southern areas,
      and indicates some important discrepancies in the clinical management of global
      CV risk among physcians working in different Italian regions.

PMID- 21186105
TI  - The association of the Mediterranean Adequacy Index with fatal coronary events in
      an Italian middle-aged male population followed for 40 years.
AB  - BACKGROUND AND AIMS: The dietary habits defined as the Mediterranean diet have
      shown to be protective for coronary heart disease (CHD) and other morbid
      conditions. The present analysis aims to test the Mediterranean Adequacy Index
      (MAI), a dietary index derived from the Mediterranean habits, versus the
      occurrence of fatal CHD events in an Italian male population followed for 40
      years. METHODS AND RESULTS: In 1965, at the time of the 5-year follow-up
      examination of the Italian Rural Areas of the Seven Countries Study, the diet was
      assessed by the dietary-history method in 1139 men aged 45-64 years, free from
      previous coronary events, in the rural communities of Crevalcore (Northern Italy)
      and Montegiorgio (Central Italy). MAI has been computed and its natural log
      (lnMAI) used for the analysis. Mortality data were collected and coded for the
      subsequent 40 years. The lnMAI was inversely associated with CHD mortality at 20
      and 40 years when entered alone in the Cox proportional hazards model and when
      adjusted for age, cigarette smoking, systolic blood pressure, serum cholesterol,
      physical activity and body mass index. The hazard ratio for 1 unit of lnMAI
      (roughly corresponding to 2.7 units of MAI) was associated with a CHD mortality
      reduction of 26% in 20 years and 21% in 40 years of follow-up, when adjusted for
      the covariates. CONCLUSIONS: In an Italian middle-aged male population, MAI
      showed the protective effect of a healthy Mediterranean Diet pattern versus the
      occurrence of fatal CHD events at 20 and 40 years.

PMID- 21186107
TI  - Nutritional intake and oxidative stress in chronic heart failure.
AB  - BACKGROUND AND AIMS: Patients with chronic heart failure (CHF) are known to be at
      risk of malnutrition, and cardiac cachexia is an adverse prognostic indicator.
      The aim of this study was to determine the dietary adequacy of CHF patients
      compared with Dietary Reference Values, to compare the nutritional intake and
      status of CHF patients to a healthy comparison group, and finally to determine
      whether nutritional intake and status depended on New York Heart Association
      (NYHA) functional class. METHODS AND RESULTS: Patients with CHF (n = 39) and a
      comparison group of 27 healthy participants, who did not have CHF, were asked to
      complete a four-day food diary, and energy and nutrient intakes were calculated.
      F(2alpha)-isoprostanes were measured in urine as an indicator of oxidative stress
      and antioxidants were measured in serum or plasma. Overall 73% of the CHF
      patients were consuming less than recommended energy intakes, and more than 50%
      of these patients were also consuming less than recommended vitamin D, selenium
      and zinc intakes. Nutrient intake (energy, vitamin B6, D, E, iron, folate and
      riboflavin) was lower in CHF patients than in the comparison group, with vitamin
      B6 and folate intake and antioxidant status decreasing, and isoprostane status
      increasing as NYHA functional class increased. CONCLUSION: The majority of CHF
      patients do not meet dietary reference values for energy and a range of
      nutrients, and nutrient intake is lower in CHF patients than in healthy
      individuals. Dietary inadequacy tends to be increased in those with more severe
      disease.

PMID- 21186106
TI  - Education modulates the association of the FTO rs9939609 polymorphism with body
      mass index and obesity risk in the Mediterranean population.
AB  - OBJECTIVE: To define whether the rs9939609 FTO (fat mass and obesity associated)
      single nucleotide polymorphism (SNP) is associated with anthropometric
      measurements and its modulation by educational level in a Mediterranean
      population. METHODS: We studied 3 independent adult samples: a random sample (n =
      1580) from the general population (GP), obese hospital patients (OHP) (n = 203)
      and elderly subjects (n = 1027) with high cardiovascular risk (HCR). Weight and
      height were directly measured. Education and physical activity (PA) were measured
      using questionnaires. RESULTS: The rs9939609 presented heterogeneous associations
      with BMI. In the GP, the minor A-allele was significantly associated with greater
      BMI, following a co-dominant pattern (P = 0.009), whereas in the OHP this
      association was recessive (P = 0.004). Conversely, we did not find a significant
      association with BMI in the HCR group (P < 0.596). In the GP we found a
      significant interaction between the FTO SNP and education (P = 0.048). In the
      stratified analysis, no association of the FTO SNP with greater BMI in university
      subjects was detected (P = 0.786), whereas the association was observed in non
      university subjects (P = 0.001). The FTO * education interaction (P = 0.020) was
      also observed in determining obesity risk in the GP. A-allele carriers had a
      greater risk of being obese only if they had no university education (OR: 1.56;
      95%CI: 1.09-2.23 for TA and OR: 2.01; 95%CI: 1.27-3.26 for AA subjects). The
      interaction of the FTO with education remained significant even after adjustment
      for PA. CONCLUSIONS: The association of the FTO SNP with greater BMI and obesity
      risk in the GP was strongly modulated by education.

PMID- 21186108
TI  - Diet, fitness and metabolic syndrome--the DR's EXTRA study.
AB  - BACKGROUND AND AIMS: To study the independent and combined associations of diet
      and cardiorespiratory fitness with the prevalence of the metabolic syndrome
      (MetS). METHODS AND RESULTS: We studied a population-based random sample of 663
      men and 671 women 57-78 years of age at baseline of an ongoing randomised
      controlled trial. Based on a 4-day food record a diet score was created according
      to goals achieved (vegetables >=400 g/day, fish >=2 servings/week, fibre >=14
      g/1000 kcal, saturated fat <10 E%/day). Cardiorespiratory fitness was measured as
      maximal oxygen uptake (VO(2 max)) in a maximal symptom-limited bicycle ergometer
      test. MetS was defined by the National Cholesterol Education Program criteria.
      The lowest prevalence of MetS (5%) was observed among individuals in the highest
      VO(2 max) tertile and achieving 3-4 dietary goals. The highest prevalence (55%)
      was observed among those in the lowest VO(2 max) tertile and achieving none of
      the dietary goals. Among individuals in the highest VO(2 max) tertile, the odds
      ratio of having MetS was 0.04 (95% CI 0.02-0.10) for those achieving 3-4 dietary
      goals, 0.07 (0.04-0.14) for those achieving 1-2 dietary goals, and 0.16 (0.07
      0.37) for those achieving none of the dietary goals compared with individuals in
      the lowest VO(2 max) tertile and achieving none of the goals after adjustment for
      confounding factors. CONCLUSION: Healthy diet and higher levels of
      cardiorespiratory fitness are associated with a reduced risk of having MetS.
      However, fitness seems to have a stronger association with MetS than diet.

PMID- 21186109
TI  - Effect of bariatric surgery on peripheral flow-mediated dilation and coronary
      microvascular function.
AB  - BACKGROUND AND AIMS: To assess the effects of bariatric surgery (BS) on
      peripheral endothelial function and on coronary microvascular dilator function.
      METHODS AND RESULTS: We studied 50 morbidly obese patients (age 38 +/- 9, 13 M)
      who underwent BS and 20 comparable obese controls (age 41 +/- 11, 6 M) without
      any evidence of cardiovascular disease. Peripheral vascular dilator function was
      assessed by brachial artery diameter changes in response to post-ischemic forearm
      hyperaemia (flow-mediated dilation, FMD). Coronary microvascular function was
      assessed by measuring coronary blood flow (CBF) velocity response to i.v.
      adenosine and to cold pressor test (CPT) in the left anterior descending coronary
      artery by transthoracic Doppler echocardiography. The tests were performed at
      baseline and at 3-month follow-up. At baseline, FMD and CBF response to adenosine
      and CPT were similar in the 2 groups. Compared to baseline, FMD at follow-up
      improved significantly in BS patients (5.9 +/- 2.7% to 8.8 +/- 2.4%, p < 0.01),
      but not in controls (6.3 +/- 3.2% vs. 6.4 +/- 3.1%, p = 0.41). Similarly, a
      significant improvement of CBF response to adenosine (1.63 +/- 0.47 to 2.45 +/-
      0.57, p < 0.01) and to CPT (1.43 +/- 0.26 to 2.13 +/- 0.55, p < 0.01) was
      observed in BS patients but not in controls (1.55 +/- 0.38 vs. 1.53 +/- 0.37, p =
      0.85; and 1.37 +/- 0.26 vs. 1.34 +/- 0.21, p = 0.48, respectively). The
      favourable vascular effects of BS were similar independently of the presence and
      changes of other known cardiovascular risk factors and of basal values and
      changes of serum C-reactive protein levels. CONCLUSIONS: Our data show that, in
      morbidly obese patients, together with peripheral endothelial function, BS also
      improves coronary microvascular function. These effects suggest global
      improvement of vascular function which can contribute significantly to the
      reduction of cardiovascular risk by BS reported in previous studies.

PMID- 21186110
TI  - Uric acid does not affect the prevalence and extent of coronary artery disease.
      Results from a prospective study.
AB  - BACKGROUND: Hyperuricemia may be involved in the atherosclerotic process due to
      endothelial dysfunction and facilitation of smooth muscle cell proliferation.
      However, debates still exist on the independent role of hyperuricemia, due to its
      association with several cardiovascular risk factors, such as hypertension,
      hyperlipidemia, obesity and insulin resistance. Thus, the aim of the current
      study was to investigate in a consecutive cohort of patients undergoing coronary
      angiography whether hyperuricemia is associated with the extent of coronary
      artery disease. METHODS AND RESULTS: Our population is represented by a total of
      1901 consecutive patients undergoing coronary angiography between May 2007 and
      January 2010 at the Azienda Ospedaliera "Maggiore della Carita", Novara, Italy.
      We additionally evaluated platelet aggregation by PFA-100 (Collagen/Epinefrine)
      and Multiplate. Quantitative coronary angiography and analysis of IMT were
      performed by experienced cardiologists who had no knowledge of the patients'
      clinical information. Higher uric acid was associated with advanced age, larger
      prevalence of male gender, diabetes, renal insufficiency, hypertension, previous
      CABG and MI, but with a lower prevalence of family history of CAD. Patients with
      high uric acid were more often on calcium antagonists, ace-inhibitors,
      angiotensin receptor antagonists, and, as expected, on diuretics. A significant
      relationship was observed between uric acid and the prevalence (OR [95% CI] =
      1.18 [1.04-1.32], p = 0.01) and severity of CAD (OR [95% CI] = 1.17 [1.03-1.33],
      p = 0.014). However, the relationship disappeared after correction for baseline
      confounding factors for both prevalence (OR [95% CI] = 1.06 [0.93-1.21], p =
      0.35) and extent of CAD (OR [95% CI] = 1.0 [0.87-1.15], p = 0.96). No
      relationship was observed between acid uric and IMT (p = 0.73) analyzed in 359
      consecutive patients. Finally, there was no relationship between uric acid and
      platelet aggregation in patients with or without aspirin therapy, as measured by
      PFA-100 and Multiplate. CONCLUSIONS: Our study showed that uric acid is not
      associated with platelet aggregation, the extent of coronary artery disease and
      IMT. Thus, waiting for the results of additional large studies, uric acid may not
      be considered as a risk factor for coronary artery disease, and its reduction by
      specific therapies may not be recommended to prevent coronary artery disease and
      atherosclerosis.

PMID- 21186111
TI  - Inaccuracy in meta-analysis on rosiglitazone and myocardial infarction.

PMID- 21186112
TI  - Receptor identification and physiological characterisation of glucagon-like
      peptide-2 in the rat heart.
AB  - BACKGROUND AND AIMS: The anorexigenic glucagon-like peptide (GLP)-2 is produced
      by intestinal L cells and released in response to food intake. It affects
      intestinal function involving G-protein-coupled receptors. To verify whether GLP
      2 acts as a cardiac modulator in mammals, we analysed, in the rat heart, the
      expression of GLP-2 receptors and the myocardial and coronary responses to GLP-2.
      METHODS AND RESULTS: GLP-2 receptors were detected on ventricular extracts by
      quantitative real-time polymerase chain reaction (Q-RT-PCR) and Western blotting.
      Cardiac GLP-2 effects were analysed on Langendorff perfused hearts. Intracellular
      GLP-2 signalling was investigated on Langendorff perfused hearts and by Western
      blotting and enzyme-linked immunosorbent assay (ELISA) on ventricular extracts.
      By immunoblotting and Q-RT-PCR, we revealed the expression of ventricular GLP-2
      receptors. Perfusion analyses showed that GLP-2 induces positive inotropism at
      low concentration (10-12 mol l(-1)), and negative inotropism and lusitropism from
      10 to 10 mol l(-1). It dose-dependently constricts coronaries. The negative
      effects of GLP-2 were independent from GLP-1 receptors, being unaffected by
      exendin-3 (9-39) amide. GLP-2-dependent negative action involves Gi/o proteins,
      associates with a reduction of intracellular cyclic adenosine monophosphate
      (cAMP), an increase in extracellular signal regulated kinases 1 and 2 (ERK1/2)
      and a decrease in phospholamban phosphorylation, but is independent from
      endothelial nitric oxide synthase (eNOS) and protein kinase G (PKG). Finally, GLP
      2 competitively antagonised beta-adrenergic stimulation. CONCLUSIONS: For the
      first time, to our knowledge, we found that: (1) the rat heart expresses
      functional GLP-2 receptors; (2) GLP-2 acts on both myocardium and coronaries,
      negatively modulating both basal and beta-adrenergic stimulated cardiac
      performance; and (3) GLP-2 effects are mediated by G-proteins and involve ERK1/2.

PMID- 21186113
TI  - A derangement of the maternal lipid profile is associated with an elevated risk
      of congenital heart disease in the offspring.
AB  - BACKGROUND AND AIMS: Maternal hyperglycaemia and hyperhomocysteinaemia are risk
      factors for congenital heart disease (CHD). These metabolic derangements and
      deranged lipid levels are associated with adult cardiovascular disease. We
      examined whether maternal lipid levels are associated with the risk of CHD
      offspring. METHODS AND RESULTS: From 2003 onwards, a case-control study was
      conducted. Participants were mothers of children with (n = 261) and without (n =
      325) CHD. At around 16 months after the index-pregnancy, maternal lipid levels
      were determined. Maternal characteristics and lipid levels were compared by
      Student's t-test. In a multivariable logistic regression model, risk estimates
      were calculated for associations between CHD and lipid levels. Adjustments were
      made for maternal age, diabetes, ethnicity, body mass index (BMI), parity,
      periconception folic acid use and total homocysteine levels. Outcome measures are
      presented in (geometric) means (p5-p95) and odds ratios (ORs) with 95% confidence
      intervals (CIs). Case mothers showed higher cholesterol (4.9 vs. 4.7 mmol l(-1),
      P < 0.05), low-density lipoprotein (LDL)-cholesterol (3.2 vs. 3.0 mmol l(-1), P <
      0.05), apolipoprotein B (84.0 vs. 80.0 mg dl(-1), P < 0.01) and homocysteine
      (10.8 vs. 10.2 MUmol l(-1), P < 0.05) than controls. LDL-cholesterol above 3.3
      mmol l(-1) (OR 1.6 (95%CI, 1.1-2.3)) and apolipoprotein B above 85.0 mg dl(-1)
      were associated with an almost twofold increased CHD risk (OR 1.8 (95%CI, 1.2
      2.6)). This was supported by elevated CHD risks per unit standard deviation
      increase in cholesterol (OR 1.2 (95% CI 1.03-1.5)), LDL-cholesterol (OR 1.3
      (95%CI, 1.1-1.6) and apolipoprotein B (OR 1.3 (95% CI 1.1-1.6)). Apolipoprotein B
      was most strongly associated with CHD risk. CONCLUSION: A mildly deranged
      maternal lipid profile is associated with an increased risk of CHD offspring.

PMID- 21186114
TI  - The role of serum adipocyte fatty acid-binding protein on the development of
      metabolic syndrome is independent of pro-inflammatory cytokines.
AB  - BACKGROUND AND AIM: Adipocyte fatty acid-binding protein (FABP4) is abundantly
      expressed in adipocytes and plays a role in glucose homeostasis. We analysed the
      relationship between serum FABP4 levels and the progression of metabolic syndrome
      in healthy adults. METHODS AND RESULTS: A total of 465 subjects were selected
      from participants in a medical check-up programme at a Health Promotion Center.
      Baseline serum FABP4 levels were measured, and the subjects were evaluated for
      the presence of metabolic syndrome (MetS) according to the recommendations of the
      American Heart Association/National Heart, Lung, and Blood Institute. The
      subjects were re-evaluated 4 years later. Baseline FABP4 concentrations were
      significantly higher in subjects with MetS than in those without MetS (P<0.001).
      At the 4-year follow-up, subjects in the highest FABP4 tertile at baseline
      exhibited higher values for body mass index, fat mass and percent body fat, as
      well as blood pressure, fasting glucose, total cholesterol, triglycerides, low
      density lipoprotein (LDL)-cholesterol, insulin, homeostasis model assessment of
      insulin resistance, monocyte chemoattractant protein-1 and tumor necrosis factor
      alpha levels (all P<0.05). The subjects with higher FABP4 levels had lower HDL
      cholesterol concentrations (P<0.05). After adjustment for age, sex, change in
      percent body fat and baseline values for other metabolic and inflammatory
      parameters, FABP4 levels at baseline were shown to be strongly associated with
      the development of MetS by year 4 (odds ratio (OR), 5.75; 95% confidence interval
      (CI), 2.71-12.23 for highest tertile vs. lowest tertile, P<0.001) CONCLUSION:
      Baseline serum FABP4 levels appear to be a significant predictor for the future
      development of MetS, independent of pro-inflammatory cytokines.

PMID- 21186115
TI  - A performance-based system for the long-term management of municipal waste
      landfills.
AB  - Landfills have been the dominant alternative for disposal of solid waste and
      there are tens of thousands of closed landfills throughout the world that require
      a long-term management strategy. In contrast to approaches based on time or
      target values, this paper describes a performance-based methodology for
      evaluation of post-closure care (PCC). Using the methodology, critical components
      of PCC at a landfill, including leachate and gas management, groundwater
      monitoring and cover integrity, are considered to determine whether a landfill
      meets defined conditions for functional stability and can transition from
      regulated PCC to a post-regulatory custodial care program representing de minimus
      care activities only. The methodology is predicated on understanding the
      biological, chemical, and physical behavior of a landfill and the presence of
      sufficient data to verify expected trends in landfill behavior. If an evaluation
      suggests that a change can be made to PCC, the landfill owner must perform
      confirmation monitoring and then surveillance monitoring at a decreasing
      frequency to verify that the change is protective of human health and the
      environment. A hypothetical case study showed that using the methodology to
      evaluate site-specific PCC requirements could result in increased environmental
      protection at comparable cost by spending available funds where they are most
      needed.

PMID- 21186116
TI  - Clinical solid waste management practices and its impact on human health and
      environment--A review.
AB  - The management of clinical solid waste (CSW) continues to be a major challenge,
      particularly, in most healthcare facilities of the developing world. Poor conduct
      and inappropriate disposal methods exercised during handling and disposal of CSW
      is increasing significant health hazards and environmental pollution due to the
      infectious nature of the waste. This article summarises a literature review into
      existing CSW management practices in the healthcare centers. The information
      gathered in this paper has been derived from the desk study of open literature
      survey. Numerous researches have been conducted on the management of CSW.
      Although, significant steps have been taken on matters related to safe handling
      and disposal of the clinical waste, but improper management practice is evident
      from the point of initial collection to the final disposal. In most cases, the
      main reasons of the mismanagement of CSW are the lack of appropriate legislation,
      lack of specialized clinical staffs, lack of awareness and effective control.
      Furthermore, most of the healthcare centers of the developing world have faced
      financial difficulties and therefore looking for cost effective disposal methods
      of clinical waste. This paper emphasizes to continue the recycle-reuse program of
      CSW materials after sterilization by using supercritical fluid carbon dioxide (SF
      CO2) sterilization technology at the point of initial collection. Emphasis is on
      the priority to inactivate the infectious micro-organisms in CSW. In that case,
      waste would not pose any threat to healthcare workers. The recycling-reuse
      program would be carried out successfully with the non-specialized clinical
      staffs. Therefore, the adoption of SF-CO2 sterilization technology in management
      of clinical solid waste can reduce exposure to infectious waste, decrease labor,
      lower costs, and yield better compliance with regulatory. Thus healthcare
      facilities can both save money and provide a safe environment for patients,
      healthcare staffs and clinical staffs.

PMID- 21186117
TI  - Online sorting of recovered wood waste by automated XRF-technology. Part I:
      detection of preservative-treated wood waste.
AB  - Waste wood is frequently contaminated with wood treatment preservatives including
      chromated copper arsenate (CCA) and alkaline copper quat (ACQ), both of which
      contain metals which contaminate recycled wood products. The objective of this
      research was to propose a design for online automated identification of As-based
      and Cu-based treated wood within the recovered wood waste stream utilizing an X
      ray fluorescence (XRF) system, and to evaluate the detection parameters of such
      system. A full-scale detection unit was used for experimentation. Two main
      parameters (operational threshold (OT) and measurement time) were evaluated to
      optimize detection efficiencies. OTs of targeted metals, As and Cu, in wood were
      reduced to 0.02 and 0.05, respectively. The optimum minimum measurement time of
      500 ms resulted in 98%, 91%, and 97% diversion of the As, Cu and Cr mass
      originally contained in wood, respectively. Comparisons with other detection
      methods show that XRF technology can potentially fulfill the need for cost
      effective processing at large facilities (>30 tons per day) which require the
      removal of As-based preservatives from their wood waste stream.

PMID- 21186118
TI  - Gas production, composition and emission at a modern disposal site receiving
      waste with a low-organic content.
AB  - AV Miljo is a modern waste disposal site receiving non-combustible waste with a
      low-organic content. The objective of the current project was to determine the
      gas generation, composition, emission, and oxidation in top covers on selected
      waste cells as well as the total methane (CH(4)) emission from the disposal site.
      The investigations focused particularly on three waste disposal cells containing
      shredder waste (cell 1.5.1), mixed industrial waste (cell 2.2.2), and mixed
      combustible waste (cell 1.3). Laboratory waste incubation experiments as well as
      gas modeling showed that significant gas generation was occurring in all three
      cells. Field analysis showed that the gas generated in the cell with mixed
      combustible waste consisted of mainly CH(4) (70%) and carbon dioxide (CO(2))
      (29%) whereas the gas generated within the shredder waste, primarily consisted of
      CH(4) (27%) and nitrogen (N(2)) (71%), containing no CO(2). The results indicated
      that the gas composition in the shredder waste was governed by chemical reactions
      as well as microbial reactions. CH(4) mass balances from three individual waste
      cells showed that a significant part (between 15% and 67%) of the CH(4) generated
      in cell 1.3 and 2.2.2 was emitted through leachate collection wells, as a result
      of the relatively impermeable covers in place at these two cells preventing
      vertical migration of the gas. At cell 1.5.1, which is un-covered, the CH(4)
      emission through the leachate system was low due to the high gas permeability of
      the shredder waste. Instead the gas was emitted through the waste resulting in
      some hotspot observations on the shredder surface with higher emission rates. The
      remaining gas that was not emitted through surfaces or the leachate collection
      system could potentially be oxidized as the measured oxidation capacity exceeded
      the potential emission rate. The whole CH(4) emission from the disposal site was
      found to be 820 +/- 202 kg CH(4)d(-1). The total emission rate through the
      leachate collection system at AV Miljo was found to be 211 kg CH(4)d(-1). This
      showed that approximately 1/4 of the emitted gas was emitted through the leachate
      collections system making the leachate collection system an important source
      controlling the overall gas migration from the site. The emission pathway for the
      remaining part of the gas was more uncertain, but emission from open cells where
      waste is being disposed of or being excavated for incineration, or from
      horizontal leachate drainage pipes placed in permeable gravel layers in the
      bottom of empty cells was likely.

PMID- 21186119
TI  - Textiles wastewater treatment using anoxic filter bed and biological wriggle bed
      ozone biological aerated filter.
AB  - In this study, the performance of the anoxic filter bed and biological wriggle
      bed-ozone biological aerated filter (AFB-BWB-O(3)-BAF) process treating real
      textile dyeing wastewater was investigated. After more than 2 month process
      operation, the average effluent COD concentration of the AFB, BWB, O(3)-BAF were
      704.8 mg/L, 294.6 mg/L and 128.8 mg/L, with HRT being 8.1-7.7h, 9.2h and 5.45 h,
      respectively. Results showed that the effluent COD concentration of the AFB
      decreased with new carriers added and the average removal COD efficiency was
      20.2%. During operation conditions, HRT of the BWB and O(3)-BAF was increased,
      resulting in a decrease in the effluent COD concentration. However, on increasing
      the HRT, the COD reduction capability expressed by the unit carrier COD removal
      loading of the BWB reactor increased, while that of the O(3)-BAF reactor
      decreased. This study is a beneficial attempt to utilize the AFB-BWB-O(3)-BAF
      combine process for textile wastewater treatment.

PMID- 21186120
TI  - Efficient production of ethanol from crude glycerol by a Klebsiella pneumoniae
      mutant strain.
AB  - A mutant strain of Klebsiella pneumoniae, termed GEM167, was obtained by gamma
      irradiation, in which glycerol metabolism was dramatically affected on exposure
      to gamma rays. Levels of metabolites of the glycerol reductive pathway, 1,3
      propanediol (1,3-PD) and 3-hydroxypropionic acid (3-HP), were decreased in the
      GEM167 strain compared to a control strain, whereas the levels of metabolites
      derived from the oxidative pathway, 2,3-butanediol (2,3-BD), ethanol, lactate,
      and succinate, were increased. Notably, ethanol production from glycerol was
      greatly enhanced upon fermentation by the mutant strain, to a maximum production
      level of 21.5 g/l, with a productivity of 0.93 g/l/h. Ethanol production level
      was further improved to 25.0 g/l upon overexpression of Zymomonas mobilis pdc and
      adhII genes encoding pyruvate decarboxylase (Pdc) and aldehyde dehydrogenase
      (Adh), respectively in the mutant strain GEM167.

PMID- 21186121
TI  - Using enriched cultures for elevation of anaerobic syntrophic interactions
      between acetogens and methanogens in a high-load continuous digester.
AB  - Volatile fatty acids (VFAs) are key intermediates in anaerobic digestion.
      Enriched acetogenic and methanogenic cultures were used for syntrophic anaerobic
      digestion of VFAs in a high-load continuous reactor fed with acetic (HAc),
      propionic (HPr) and butyric (HBu) acids at maximum concentrations of 5, 3 and 4
      g/L, respectively. Interactive effects of HPr, HBu and HAc were analyzed.
      Furthermore, hydraulic retention time (HRT) and methanogen to acetogen population
      ratio (M/A) were investigated as key microbiological and operating variables of
      VFA anaerobic degradations. Optimum conditions were found to be HPr=1125.0mg/L,
      HBu=1833.4 mg/L, HAc=1727.4 mg/L, HRT=21 h and M/A=2.5 (corresponding to maximum
      VFA removal and biogas production rate (BPR)). Results of verification
      experiments and predicted values from fitted correlations were in close agreement
      at 95% confidence interval. HRT and M/A had positive effects on VFA removal and
      BPR. M/A was the most important factor that affected BPR. All VFAs inhibited VFA
      removals.

PMID- 21186122
TI  - Bioconversion of crude glycerol to glycolipids in Ustilago maydis.
AB  - Ustilago maydis is known to produce glycolipid-type biosurfactants. Here, we show
      that U. maydis is able to efficiently convert biodiesel-derived crude glycerol to
      glycolipids. We have optimized the medium composition and environmental factors
      for bioconversion of crude glycerol to glycolipids. The synthetic medium (MinCG)
      contains 50 g L(-1) crude glycerol and 20.3 mg L(-1) ammonium citrate as the
      carbon and nitrogen sources, respectively. The supplementation of trace amount of
      amino acids, Group-B vitamins and precursors of glycolipids, mannose and
      erythritol, also improved the final yield. At pH 4.0 and 30 degrees C, 32.1 g L(
      1) total glycolipids was produced in a 8.2-day fed-batch bioprocess. Methanol at
      2% or above severely inhibited cell growth and production of glycolipids. Our
      results suggest that U. maydis is an excellent host for the bioconversion of
      crude glycerol to value-added products.

PMID- 21186123
TI  - Discovery of a series of potent arylthiadiazole H(3) antagonists.
AB  - A series of 2-piperidinopiperidine-5-arylthiadiazoles was synthesized and
      subjected to a structure-activity relationship (SAR) investigation. The potency
      of this series was improved to the single digit nanomolar range. The key analogs
      were shown to be free of P450 issues, and they also maintained good ex vivo
      activity and brain penetration.

PMID- 21186124
TI  - Symptomatic dystrophinopathies in female children.
AB  - Although manifesting female carriers of dystrophinopathies have been documented
      in adults, there are few reports of females presenting with symptomatic
      dystrophinopathies during childhood. The Canadian Pediatric Neuromuscular Group
      identified and characterized nine cases of female children 16 years or younger
      with genetically and/or histologically confirmed symptomatic dystrophinopathy,
      with an age range of 2-10 years at presentation. Presenting symptoms included
      proximal muscle weakness (6/9), calf pseudohypertrophy (5/9), abnormal gait (5/9)
      and myalgias (5/9). Five patients were noted to have significant behavioural and
      learning issues. The patients had a delay in diagnosis of 4 years from symptom
      onset. Skewed X inactivation was noted in 5/9 patients, while one patient had X
      inactivation levels in the normal range. Two of the patients were found to have
      X/autosome translocation, one of whom also had skewed X-inactivation. Increased
      awareness of manifesting females with dystrophinopathies will allow for earlier
      diagnosis and appropriate management for this rare group of patients.

PMID- 21186125
TI  - Physiological and phytochemical response to drought stress of German chamomile
      (Matricaria recutita L.).
AB  - In arid and semi-arid regions where water availability is a major limitation,
      using plants with low water consumption is one way to manage available water
      efficiently. Chamomile (Matricaria recutita L.) may be considered as an
      economical crop for fields with water scarcity due to its considerable
      adaptability to a wide range of climates and soils. A field experiment was
      conducted during 2007-2008 using complete randomized block design with four
      replications in order to evaluate the effect of drought stress on agro
      morphological characters (fresh flower weight, dried flower yield, shoot weight
      and root weight), oil content, oil composition and apigenin content of chamomile.
      Drought stress had four different levels of soil moisture depletion (30%, 50%,
      70% and 90%). Analysis of variance showed that drought stress decreased plant
      height, flower yield, shoot weight and apigenin content but it had no significant
      effect on oil content or oil composition. Impacts of drought stress on growth
      indices were evaluated as well and the results indicated that plant managed to
      maintain potential for biomass production under the drought stress. Growth
      analysis results as well as phytochemical properties of this plant showed that
      despite decrease in agronomical traits, chamomile could be proposed as a moderate
      drought resistant medicinal plant with a reasonable performance.

PMID- 21186126
TI  - Risk of acute kidney injury after minimally invasive transapical aortic valve
      implantation in 270 patients.
AB  - OBJECTIVE: Contrast agent is a potential risk factor for acute kidney injury
      (AKI). Little is known about the incidence of contrast-induced nephropathy (CIN)
      after trans-apical aortic valve implantation (TA-AVI) and on the impact of
      contrast exposure during preoperative computed tomography (CT) scan and cardiac
      catheterization. METHODS: A total of 270 consecutive high-risk patients received
      TA-AVI for symptomatic aortic valve stenosis during a 3-year period. Different
      preoperative, peri-procedural, and postoperative variables were analyzed by uni-
      and multivariate logistic regression concerning incidence of early (<7 days) AKI
      and need for renal replacement therapy (RRT). Nine patients on chronic
      preoperative dialysis were excluded. RESULTS: Mean age was 82 +/- 5.8 years, 71%
      were female. LogEuroSCORE (European System for Cardiac Operative Risk Evaluation)
      and STS Score were 31.4 +/- 15.6% and 12.1 +/- 7.4%, respectively. Preoperative
      estimated glomerular filtration rate (eGFR) <60 ml min(-1) was present in 35.2%.
      CT scan and cardiac catheterization within 7 days before TA-AVI were performed in
      43.7% and 20.3% of the patients and were associated with a mean contrast-agent
      exposition of 110 +/- 21 ml for CT scans and 91 +/- 65 ml for cardiac
      catheterization. Regarding the postoperative renal outcome, an improved or at
      least stable eGFR was seen in more than 50% of the patients. Intra-operative
      contrast-agent application was 99 +/- 64 ml and correlated significantly to the
      development of postoperative AKI and need for RRT (p=0.013 and p=0.003).
      Postoperative RRT was required in 15.7%. Chronic renal insufficiency (odds ratio
      (OR)=6.8, p=0.025) and number of blood transfusions (OR=8.8, p=0.009) were
      independent risk factors for RRT. Postoperative AKI occurred in 16.1% and intra
      operative contrast-agent burden >99 ml (OR=2.3, p=0.038), new thrombocytopenia
      (OR=4.4, p=0.005) and pathological leucocyte count (OR=2.8, p=0.009) were
      independent risk factors for this event. Early (within 1-7 days before TA-AVI)
      preoperative CT and cardiac catheterization did not significantly increase
      incidence of RRT or AKI. Short-term and long-term survival was explicitly lower
      in the AKI and in the RRT groups (p<0.001 each). CONCLUSIONS: GFR improves after
      TA-AVI. Postoperative AKI and RRT depend on the amount of intra-operative
      contrast agent. These results strongly support the need for intra-operative tools
      to reduce contrast-agent exposition during TA-AVI.

PMID- 21186127
TI  - Identifying potential heart donors among newborns undergoing circulatory
      determination of death.
AB  - BACKGROUND: Infants younger than 1 year old have the highest heart transplant
      wait-list mortality. Transplantation from donors after circulatory determination
      of death (DCDD) is an innovative new option for these patients. We examined the
      potential for heart donation in neonatal intensive care unit (NICU) patients
      undergoing elective withdrawal of life support. METHODS: Medical records of all
      patients who died between June 2003 and June 2008 in our 84-bed NICU were
      reviewed. The mode of death among potential organ donors (weight > 2.5 kg) was
      categorized into 4 groups: Died despite cardiopulmonary resuscitation (CPR), do
      not resuscitate (DNR) status, brain death, or withdrawal of life support.
      Patients undergoing planned life-support withdrawal were evaluated for DCDD
      potential. RESULTS: Of 266 NICU deaths during the study period, 117 patients
      weighed more than 2.5 kg at the time of death, of whom 15 (13%) died despite CPR,
      and 33 (28%) were DNR. No brain deaths occurred; consequently, no conventional
      organ donation resulted. Of 69 infants (59%) who died after withdrawal, 53 were
      excluded as potential donors due to active infection, cardiac dysfunction, or
      congenital heart disease. Among the remaining 16, median time from withdrawal to
      death was 31 minutes (range, < 1-310 minutes). Five infants (4.3% of deaths in
      babies > 2.5 kg) died within 30 minutes, had good cardiac function, and could
      have been potential DCDD heart donors. CONCLUSIONS: Among NICU patients withdrawn
      from life support during a 5-year period, 4.3% would have been suitable heart
      donors after circulatory determination of death. Implementing a NICU DCDD program
      could markedly expand the donor pool and reduce short-term wait-list mortality
      for infant heart transplantation.

PMID- 21186128
TI  - Mild exercise early in life produces changes in bone size and strength but not
      density in proximal phalangeal, third metacarpal and third carpal bones of foals.
AB  - Exercise or lack of it in early life affects chondro-osseous development. Two
      groups of horses were used to investigate the effects of age and exercise regimen
      on bone parameters of diaphyseal, metaphyseal, epiphyseal and cuboidal bones of
      the distal limb of Thoroughbreds. One group had exercised only spontaneously from
      an early age at pasture (PASTEX group), while the other group of horses were
      exposed to a 30% greater workload through additional defined exercise (CONDEX).
      Longitudinal data from peripheral quantitative computed tomography (pQCT) were
      obtained from eight scan sites of the left forelimb (proximal phalangeal (P(p); 1
      site), third metacarpal (Mc3; six sites) and third carpal (C(3); one site) bones)
      of 32 Thoroughbred foals scanned five times from ~3 weeks to 17 months of age.
      The primary outcome measures were bone mineral content (BMC), bone area (BA), and
      periosteal circumference (Peri C) in diaphyseal bone, with cortical thickness
      (CortTh), volumetric bone mineral density (BMD(v)) and a bone strength index
      (SSI) also being analysed. At the P(p) site within the model there was a
      significant effect (P=0.00-0.025) of conditioning exercise increasing bone
      parameters, except endosteal circumference (Endo C) and BMD(v). The BMC, BA, and
      SSI of P(p) were significantly greater in the CONDEX than PASTEX groups at 12 and
      17 months (P=0.015-0.042) and CortTh at 17 months (P=0.033). At the M55 site of
      Mc3 BMC, BA and SSI (P=0.02-0.04), and at the M33 site, SSI (P=0.05) were higher
      in the CONDEX than PASTEX group. The adaptive responses, consistent with
      diaphyseal strengthening, were more marked in the diaphysis of P(p) than Mc3. In
      the Mc3, metaphysis, trabecular BMD(v) was less in the CONDEX than PASTEX group,
      associated with greater bone mineral accretion in the outer cortical-sub-cortical
      bone in the CONDEX group. There were no significant between-group differences in
      any epiphyseal or cuboidal bone parameter. Although the early imposed exercise
      regimen was not intensive, it had significant effects on diaphyseal bone
      strength, through change in size but not bone density.

PMID- 21186129
TI  - Job strain, work characteristics and back pain: a study in a university hospital.
AB  - OBJECTIVES: The demand-control-support "job strain" model is frequently used in
      occupational health research. We sought to explore the relationship between job
      strain and back pain. METHOD: One thousand two hundred and ninety-eight
      collaborators of a Swiss teaching hospital responded to a cross-sectional
      questionnaire survey that measured job strain, the occurrence of back pain as
      well as the characteristics and consequences of this pain. RESULTS: Job strain
      computed with both psychological and physical demands was strongly and
      significantly associated with various measures of back pain. These associations
      displayed a dose-response pattern, and remained strong even after adjustment for
      job characteristics and professional categories. In contrast, separate dimensions
      of job strain (except physical demands) and job strain computed with only
      psychological demands did not remain significantly associated with back pain
      after adjustment for other variables. CONCLUSION: Our results support the
      findings linking back pain to job strain. Moreover, the relationship between back
      pain and job strain is much stronger if job strain includes both psychological
      and physical demands. Results of this study suggest that workplace interventions
      that aim to reduce job strain may help prevent back pain and may alleviate the
      personal, social, and economic burden attributable to back pain.

PMID- 21186130
TI  - Analysis of the stabilities of hexameric amyloid-beta(1-42) models using discrete
      molecular dynamics simulations.
AB  - Amyloid-beta (Abeta) oligomers appear to play a pivotal role in Alzheimer's
      disease. A 42 residue long alloform, Abeta42, is closely related to etiology of
      the disease. In vitro results show evidences of hexamers; however structures of
      these hexamers have not been resolved experimentally. Here, we use discrete
      molecular dynamics (DMD) to analyze long duration stabilities of Abeta42 hexamer
      models developed previously in our lab. The hydrophobic core of these models is a
      six-stranded beta-barrel with 3-fold radial symmetry formed by residues 30-40.
      This core is shielded from water by residues 1-28. The nine models we analyzed
      differ by the relative positions of the core beta-strands, and whether the other
      segments surrounding the core contain alpha helices or beta-strands. A model of
      an annular protofibril composed of 36 Abeta peptides was also simulated. Results
      of these model simulations were compared with results of aggregation simulations
      that started from six well separated random coils of Abeta42 and with simulations
      of two known beta-barrel structures. These results can be categorized into three
      groups: stable models with properties similar or superior to those of
      experimentally determined beta-barrel proteins, aggregation-prone models, and an
      amorphous aggregate from random coils. Conformations at the end of the simulation
      for aggregation-prone models have exposed hydrophobic core with dangling beta
      strands on the surface. Hydrogen bond patterns within the beta-barrel were a
      critical factor for stability of the beta-barrel models. Aggregation-prone
      conformations imply that the association of these hexamers may be possible, which
      could lead to the formation of larger assemblies.

PMID- 21186131
TI  - Comparison of digital and optical hand-held refractometers for the measurement of
      feline urine specific gravity.
AB  - Measuring urine specific gravity (USG) is an important component of urine
      analysis as it evaluates renal concentrating capability. The objective of this
      study was to quantify the difference in USG values between a hand-held optical
      analogue refractometer and a cat-specific digital instrument. Urine samples from
      55 cats were assessed. There was a statistically significant difference between
      these two refractometers (P<0.001), with the optical refractometer (mean
      USG=1.031) consistently reading higher than the digital refractometer (mean
      USG=1.027). Results for a random subset of the samples (n=10) were compared with
      urine osmolality and both the optical and digital instruments demonstrated
      excellent correlation. While an accurate USG reading is important, it is unlikely
      that the statistical significance between the two instruments is clinically
      significant and, therefore, unlikely to result in a change in patient evaluation
      or treatment plans. While both the digital and optimal refractometers are highly
      correlated to the urine osmolality, making both devices valid for assessment of
      USG in clinical practice, this digital device is easier to read and eliminates
      the variability of subjective interpretation.

PMID- 21186132
TI  - [Septo-optic dysplasia (De Morsier's syndrome). About one case discovered during
      the pregnancy].
AB  - The authors report a case of septo-optic dysplasia discovered during the
      pregnancy without another abnormality. It's a rare cerebral abnormality that is
      characterized by an absence of septum pellucidum associated to a hypoplasia of
      ways and optic chiasm to variable degrees. Discovery is often made for adulthood.
      Future is extremely wide. It is determined with the arisen to different degrees
      of incapacity of Pituitary gland, psychomotor delay of variable intensity with
      mental deficiency, a visual confusion, and a confusion of the regulation of the
      temperature.

PMID- 21186133
TI  - [Hypoactive sexual desire disorder, HSDD].
AB  - Hypoactive Sexual Desire Disorder (HSDD) is the most common Female Sexual
      Dysfunction (FSD) affecting adult women of any age, including postmenopausal
      women. HSDD may have significant effects on the relationships and emotional
      balance of women and constitutes the most common form of FSD observed in clinical
      practice. HSDD is characterised by a deficiency or lack of sexual fantasies and
      desire for sexual activity, causing serious distress or interpersonal
      difficulties, and it is not exclusively caused by the effects of another
      psychiatric disorder, pathology or substance (such as medication). HSDD
      pathophysiology is not yet well understood, but it is thought to involve an
      imbalance between factors controlling inhibition and excitation of sexual desire
      in the brain. Many physicians are reluctant to discuss sexual desire problems
      with their patients for various reasons, such as insufficient knowledge of the
      field, an absence of efficient treatments and time constraints. Even though
      current treatment options are limited, a better understanding of the
      physiopathology behind HSDD may help develop new therapies.

PMID- 21186134
TI  - Agglomeration and rapid ascent of microbubbles by ultrasonic irradiation.
AB  - Microbubbles have some different characteristics from conventional bubbles. To
      apply the useful properties for gas-liquid contact operation in industry,
      however, a separate technology of microbubbles has to be realized. In this study,
      promotion of microbubble separation using ultrasound was proposed. By irradiating
      with ultrasound, milky white microbubbles suspended solution changed
      instantaneously to be clear. The interesting behavior of microbubbles observed in
      the ultrasonic field was investigated by microscopic and macroscopic
      visualizations. The rapid ascent of microbubbles was caused by their
      agglomeration, where the Bjerknes force of attraction and electrical repulsive
      force on microbubble surface acted. Ultrasonic irradiation into microbubble
      suspended solution was very useful for dynamic operation of microbubbles.

PMID- 21186135
TI  - Patient versus informant reporting of ICD symptoms in Parkinson's disease using
      the QUIP: validity and variability.
AB  - Questions exist regarding the validity of patient-reporting of psychiatric
      symptoms in Parkinson's disease (PD). We assessed observer variability and
      validity in reporting of impulse control disorder (ICD) symptoms in PD by using
      the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease
      (QUIP). PD patients and their informants (71 pairs) completed the QUIP to assess
      four ICDs (compulsive gambling, buying, sexual behavior, and eating) in patients.
      Trained raters then administered a diagnostic interview. Sensitivity of the QUIP
      for a diagnosed ICD was 100% for both patient- and informant-completed
      instruments, and specificity was 75% for both raters. Approximately 40% of
      patients without an ICD diagnosis had a positive QUIP, suggesting that many PD
      patients experience subsyndromal ICD symptoms that require ongoing monitoring.
      Agreement between patient- and informant-reporting of any ICD behaviors on the
      QUIP was moderate (kappa=0.408), and for individual ICDs was highest for gambling
      (kappa=0.550). Overall, a negative QUIP from either the patient or informant
      rules out the possibility of an ICD, while a positive QUIP requires a follow-up
      diagnostic interview and ongoing monitoring to determine if symptoms currently
      are, or in the future become, clinically significant.

PMID- 21186136
TI  - Structural, thermal and optical characterization of an organic NLO material-
      benzaldehyde thiosemicarbazone monohydrate single crystals.
AB  - Single crystals of the organic NLO material, benzaldehyde thiosemicarbazone
      (BTSC) monohydrate, were grown by slow evaporation method. Solubility of BTSC
      monohydrate was determined in ethanol at different temperatures. The grown
      crystals were characterized by single crystal X-ray diffraction analysis to
      determine the cell parameters and by FT-IR technique to study the presence of the
      functional groups. Thermogravimetric and differential thermal analyses reveal the
      thermal stability of the crystal. UV-vis-NIR spectrum shows excellent
      transmission in the region of 200-1100 nm. Theoretical calculations were carried
      out to determine the linear optical constants such as extinction coefficient and
      refractive index. Further the optical nonlinearities of BTSC have been
      investigated by Z-scan technique with He-Ne laser radiation of wavelength 632.8
      nm. Mechanical properties of the grown crystal were studied using Vickers
      microhardness tester. Second harmonic generation efficiency of the powdered BTSC
      monohydrate was tested using Nd:YAG laser and it is found to be ~5.3 times that
      of potassium dihydrogen orthophosphate.

PMID- 21186137
TI  - Nitro-substituted 3,3'-bis(indolyl)methane derivatives as anion receptors:
      electron-withdrawing effect and tunability of anion binding properties.
AB  - A series of nitro-substituted 3,3'-bis-indolyl phenylmethane derivatives were
      synthesized and their anion binding properties were investigated in detail. The
      introduction of the electron-withdrawing nitro group into indole unit and/or meso
      phenyl ring, which leads to the increased acidity of indole NH and meso-position
      CH proton, has a positive effect on anion binding. The nitro-substituted
      bis(indolyl)methane receptors exhibited selective colorimetric sensing of F-
      anion, as revealed by the notable color and spectral changes, rationally due to
      the deprotonation of the indole NH of the receptor. Meanwhile, the additive
      introduction of the nitro substituents on the meso-phenyl ring of
      bis(indolyl)methane can lead to the deprotonation of the meso-position CH and
      further induce an irreversible oxidation process obtaining bis(indolyl)methene
      product in the F- anion sensing system.

PMID- 21186139
TI  - The effect of postoperative pain management program on improving nurses'
      knowledge and attitudes toward pain.
AB  - Effective postoperative pain treatment is an essential component to good quality
      of care. The purpose of this study was to explore nurses' knowledge of and
      attitudes toward pain in surgical wards before and after implementation of a
      postoperative management program at a university hospital in Jordan. The program
      consisted of an education program for nurses, and its effect was evaluated by
      using a pre- and post-intervention design. Sixty five registered nurses were
      asked to respond to a 21 items questionnaire, and a total of 240 patients'
      records were audited. After implementation of the program, the mean scores for
      all the questionnaire items were found to increase to 75%, with an average of
      16/21 for the correct answers. There was a statistically significant difference
      (p < 0.05) between the number of correct answers between nurses' responses in the
      pre-intervention phase and their responses in the post-intervention phase for
      most of the questionnaire items. Also, there was a statistically significant
      improvement in the documentation of patients' care in 85% of the audited
      patients' records. It was recommended to introduce an acute pain services (APS)
      using a well established and safe pain management routines to increase the
      quality of care.

PMID- 21186138
TI  - Fluorosurfactant-capped gold nanoparticles-enhanced chemiluminescence from
      hydrogen peroxide-hydroxide and hydrogen peroxide-bicarbonate in presence of
      cobalt(II).
AB  - Nonionic fluorosurfactant (FSN)-capped gold nanoparticles (GNPs) remain
      excellently stable at a wider pH range and high ionic strength, which is useful
      to investigate some CL systems involved in high salt and a strict pH range. In
      this study, we utilized FSN-capped GNPs of different sizes to distinguish the
      emitting species from H2O2-Co2+-NaOH and H2O2-Co2+-NaHCO3 systems. When the pH of
      FSN-capped gold colloidal solution was adjusted to 10.2 by dropwise addition of
      0.05 M NaOH, the CL intensity of H2O2-Co2+-NaHCO3 system was enhanced 6-fold or
      60-fold respectively in the presence of FSN-capped 14 nm or 69 nm GNPs with
      comparison to H2O2-Co2+-NaOH. The variation of CL spectra and UV-vis spectra, as
      well as the quenching effect of reactive oxygen species scavengers were studied
      in detail to understand the CL enhancement mechanisms of FSN-capped GNPs on the
      two systems. For H2O2-Co2+-NaOH system, the gold(I) complexes intermediate and
      singlet oxygen dimol species were proposed as the emitting species. The excited
      states of the carbon dioxide dimers and singlet oxygen dimol species were
      considered responsible for the light emission of H2O2-Co2+-NaHCO3 system. To our
      knowledge, this work is the first time to study the two CL systems simultaneously
      using nanoparticles.

PMID- 21186142
TI  - Insulin during pregnancy, labour and delivery.
AB  - Optimal glycaemic control is of the utmost importance to achieve the best
      possible outcome of a pregnancy complicated by diabetes. This holds for
      pregnancies in women with preconceptional type 1 or type 2 diabetes as well as
      for pregnancies complicated by gestational diabetes. Glycaemic control is
      conventionally expressed in the HbA1c value but the HbA1c value does not
      completely capture the complexity of glycaemic control. The daily glucose profile
      measured by the patients themselves through measurements performed in capillary
      blood obtained by finger stick provides valuable information needed to adjust
      insulin therapy. Hypoglycaemia is the major threat to the pregnant woman or the
      woman with tight glycaemic control in the run-up to pregnancy. Repetitive
      hypoglycaemia can lead to hypoglycaemia unawareness, which is reversible with
      prevention of hypoglycaemia. A delicate balance should be struck between
      preventing hyperglycaemia and hypoglycaemia. Insulin requirements are not uniform
      across the day: it is low during the night with a more or less pronounced rise at
      dawn, followed by a gradual decrease during the remainder of the day. A basal
      amount of insulin is needed to regulate the endogenous glucose production, short
      acting insulin shots are needed to handle exogenous glucose loads. Insulin
      therapy means two choices: the type of insulin used and the method of insulin
      administration. Regarding the type of insulin, the choice is between human and
      analogue insulins. The analogue short-acting insulin aspart has been shown to be
      safe during pregnancy in a randomised trial and has received registration for
      this indication; the short-acting analogue insulin lispro has been shown to be
      safe in observational studies. No such information is available on the long
      acting insulin analogues detemir and glargine and both are prescribed off-label
      with human long-acting insulin as obvious alternatives. Randomised trials have
      not been able to show superiority of continuous subcutaneous insulin
      administration (CSII (insulin pump)) over intensive insulin injection therapy
      (multiple-dose insulin (MDI)) on any maternal or foeto-neonatal end point.
      However, group sizes were far too small to allow assessment of superiority and
      issues such as manageability of the disease and quality of life were never
      assessed. These two issues are of major importance to patients. The first
      trimester is often the period of most hypoglycaemic events, and insulin therapy
      should be especially closely monitored and adjusted in this period. After
      midterm, insulin requirements increase. Continuous glucose monitoring can offer
      better insights into the glycaemic profile than self-monitoring of blood glucose
      levels by the patients but the place of these new monitoring techniques has yet
      to be established more clearly. Insulin therapy during labour means short-acting
      insulin adjusted to achieve glucose levels between 4 and 8 mmol l(-1) to prevent
      neonatal hypoglycaemia as much as possible. After delivery, glycaemic control
      must be relaxed to prevent hypoglycaemia, especially in women who breastfeed.

PMID- 21186143
TI  - Derivatization of carbohydrates for GC and GC-MS analyses.
AB  - GC and GC-MS are excellent techniques for the analysis of carbohydrates;
      nevertheless the preparation of adequate derivatives is necessary. The different
      functional groups that can be found and the diversity of samples require specific
      methods. This review aims to collect the most important methodologies currently
      used, either published as new procedures or as new applications, for the analysis
      of carbohydrates. A high diversity of compounds with diverse functionalities has
      been selected: neutral carbohydrates (saccharides and polyalcohols), sugar acids,
      amino and iminosugars, polysaccharides, glycosides, glycoconjugates,
      anhydrosugars, difructose anhydrides and products resulting of Maillard reaction
      (osuloses, Amadori compounds). Chiral analysis has also been considered,
      describing the use of diastereomers and derivatives to be eluted on chiral
      stationary phases.

PMID- 21186144
TI  - [Iron, hepcidin and chronic kidney disease].
AB  - Iron deficiency is commonly observed in chronic kidney disease. Blood loss and
      iron consumption under erythropiesis activating agents (ESA) induce absolute
      deficiency whereas defect of iron intestinal absorption and storage release
      account for functional deficiency. High hepcidin plasma levels are probably
      induced by inflammatory process and can explain functional deficiency. However,
      hepcidin is negatively correlated with ESA needs and hepcidin expression is
      influenced by other factors as degree of renal insufficiency, iron pool,
      treatments (iron IV and ESA). IV iron is the common therapeutic approach of iron
      deficiency and only normalized iron marrow supply cannot account for his
      efficiency. New IV iron products allow us to conceive new therapeutic schemes.
      Hepcidin inhibition is another therapeutic alternative.

PMID- 21186146
TI  - Lymphedema in patients with head and neck cancer.
AB  - PURPOSE/OBJECTIVES: to describe the current state of the science on secondary
      lymphedema in patients with head and neck cancer. DATA SOURCES: published journal
      articles and books and data from the National Cancer Institute, the American
      Cancer Society, and other healthcare-related professional association Web sites.
      DATA SYNTHESIS: survivors of head and neck cancer may develop secondary
      lymphedema as a result of the cancer or its treatment. Secondary lymphedema may
      involve external (e.g., submental area) and internal (e.g., laryngeal,
      pharyngeal, oral cavity) structures. Although lymphedema affects highly visible
      anatomic sites (e.g., face, neck), and profoundly influences critical physical
      functions (e.g., speech, breathing, swallowing, cervical range of motion),
      research regarding this issue is lacking. Studies are needed to address a variety
      of vital questions, including incidence and prevalence, optimal measurement
      techniques, associated symptom burden, functional loss, and psychosocial impact.
      CONCLUSIONS: secondary lymphedema in patients with head and neck cancer is a
      significant but understudied issue. IMPLICATIONS FOR NURSING: a need exists to
      systematically examine secondary lymphedema related to treatment for head and
      neck cancer and address gaps in the current literature, such as symptom burden,
      effects on body functions, and influences on quality of life. Oncology nurses and
      other healthcare professionals should have empirical evidence to help them manage
      lymphedema after head and neck cancer treatment.

PMID- 21186147
TI  - Oncology nurses' perspectives on the state of cancer survivorship care: current
      practice and barriers to implementation.
AB  - PURPOSE/OBJECTIVES: to describe current survivorship care from the perspectives
      of oncology nurses. DESIGN: descriptive. SETTING: e-mail invitation to Web-based
      survey. SAMPLE: 399 Oncology Nursing Society members providing care for patients
      initially treated more than one year previously. METHODS: an online survey was
      used to evaluate current aspects of survivorship care. MAIN RESEARCH VARIABLES:
      practice settings, services provided, and barriers to delivering survivorship
      care. FINDINGS: few nurses (27%) worked in settings with a formal survivorship
      program. Several program components were provided significantly more often in
      outpatient settings, pediatric facilities, and workplaces with a formal
      survivorship program. At the transition from acute to follow-up care, the
      survivorship nursing care provided most often was scheduling for ongoing
      monitoring (71%) and the least likely was assistance for employment or legal
      issues (16%). The greatest barriers to providing survivorship care were lack of
      time and funding (46%). Among nurses new to oncology (fewer than five years), 49%
      indicated they lacked sufficient knowledge compared to 36% of nurses with more
      than five years of oncology experience. CONCLUSIONS: findings describe current
      aspects of survivorship care across practice settings. Nurses reported that the
      greatest barriers are lack of time, funding, and lack of knowledge about
      survivorship issues. IMPLICATIONS FOR NURSING: a need exists for education to
      enhance knowledge and skills of nurses who will provide survivorship care.
      Research is warranted to develop empirically supported guidelines and care
      delivery models that address the barriers to providing survivorship services.

PMID- 21186149
TI  - The role of information sources and objective risk status on lymphedema risk
      minimization behaviors in women recently diagnosed with breast cancer.
AB  - PURPOSE/OBJECTIVES: to assess the role of education sources and objective risk
      status on knowledge and practice of lymphedema risk-minimization behaviors among
      women recently diagnosed with breast cancer. RESEARCH APPROACH: prospective
      survey. SETTING: a hospital in Sydney, Australia. PARTICIPANTS: 106 women
      recently diagnosed with breast cancer at increased risk for developing lymphedema
      following lymph node dissection. METHODOLOGIC APPROACH: a questionnaire
      administered at the time of surgery and three months after surgery measured
      demographics, lymphedema knowledge, lymphedema information sources used, and
      adherence to risk-minimization recommendations. MAIN RESEARCH VARIABLES:
      lymphedema knowledge, source of information used, objective lymphedema risk, and
      adherence to risk-minimization behaviors. FINDINGS: knowledge was high and
      increased over time. Lymphedema information from the clinic (e.g., brochures,
      nursing staff) was the most cited source. Adherence to recommendations was
      moderate; nonadherence was mostly for behaviors requiring regular enactment.
      Regression analysis revealed that only receipt of information from nursing staff
      and lymphedema knowledge three months after surgery were significant predictors
      of risk-minimization behaviors. CONCLUSIONS: exposing women to lymphedema risk
      information at the time of breast cancer diagnosis facilitates increased
      awareness and enactment of risk-minimization behaviors. Nursing staff play a key
      role in disseminating this information and in convincing women to perform the
      recommendations. INTERPRETATION: provision of lymphedema education by breast
      clinic staff is critical to ensure that women realize the importance of early
      detection and treatment. Reminder booster sessions by nursing staff may be
      beneficial particularly for longer-term knowledge retention and adherence to
      recommended behaviors.

PMID- 21186148
TI  - Sensory perceptions of patients with cancer undergoing surgical insertion of a
      totally implantable venous access device: a qualitative, exploratory study.
AB  - PURPOSE/OBJECTIVES: to investigate sensory perceptions of patients who underwent
      insertion of a totally implantable venous access device (TIVAD) under local
      anesthesia. RESEARCH APPROACH: qualitative, exploratory study. SETTING: tertiary
      care center in Belgium. PARTICIPANTS: 20 adult patients with cancer or
      hematologic disease undergoing a first-time TIVAD insertion. METHODOLOGIC
      APPROACH: immediately after insertion, patients were asked to describe their
      sensory perceptions during each of four phases. Descriptions were documented in a
      sensory information grid (SIG) that was composed of a row and column matrix of
      entries for the four phases of the procedure and the five sensory modalities.
      Verbatim descriptions of patients were assigned labels using a descriptive coding
      process. MAIN RESEARCH VARIABLES: sensory perceptions in the modalities of
      hearing, sight, touch, smell, and taste. FINDINGS: patients experienced many
      sensory perceptions that mainly occurred during preparation of the patients and
      surgical equipment (phase 2) and during the actual TIVAD insertion (phase 3).
      Patients perceived fewer olfactory sensations. No taste perceptions were
      mentioned. CONCLUSIONS: patients reported numerous sensory perceptions during
      TIVAD insertion. The SIG method proved suitable for assessing and documenting
      patients' sensory perceptions. INTERPRETATION: the reported descriptions can be
      used (a) to develop a structured questionnaire to quantitatively assess sensory
      perceptions and (b) to prepare patients for what to expect with regard to sensory
      information experienced before, during, and after TIVAD insertion. This method
      for exploring and documenting sensory perceptions might be applicable to other
      diagnostic or therapeutic interventions.

PMID- 21186150
TI  - Striving to respond to palliative care patients' pain at home: a puzzle for
      family caregivers.
AB  - PURPOSE/OBJECTIVES: to describe the types of pain patients in palliative care at
      home experience and how family caregivers assess them and intervene. RESEARCH
      APPROACH: qualitative using grounded theory. SETTING: family caregivers' homes.
      PARTICIPANTS: 24 family caregivers of patients with advanced cancer receiving
      palliative care at home. METHODOLOGIC APPROACH: semistructured interviews and
      field notes. Data analysis used Strauss and Corbin's recommendations for open,
      axial, and selective coding. MAIN RESEARCH VARIABLES: pain, pain management,
      family caregivers, palliative care, and home care. FINDINGS: caregivers assessed
      different types of pain and, therefore, were experimenting with different types
      of interventions. Not all family caregivers were able to distinguish between the
      different pains afflicting patients, and, consequently, were not selecting the
      most appropriate interventions. This often led to poorly managed pain and
      frustrated family caregivers. CONCLUSIONS: The accurate assessment of the types
      of pain the patient is experiencing, coupled with the most appropriate
      intervention for pain control, is critical for optimal pain relief as well as
      supporting the confidence and feelings of family caregivers who are undertaking
      the complex process of cancer pain management. INTERPRETATION: nurses involved
      with patients receiving palliative care and their family caregivers should be
      aware of all types of pain experienced by the patient and how caregivers are
      managing the pain. Nurses should be knowledgeable about different pain relief
      interventions to help family caregivers obtain accurate information, understand
      their options, and administer these interventions safely and effectively.

PMID- 21186151
TI  - Measuring stigma in people with lung cancer: psychometric testing of the cataldo
      lung cancer stigma scale.
AB  - PURPOSE/OBJECTIVES: to develop an instrument to measure the stigma perceived by
      people with lung cancer based on the HIV Stigma Scale. DESIGN: psychometric
      analysis. SETTING: online survey. SAMPLE: 186 patients with lung cancer. METHODS:
      an exploratory factor analysis with a common factor model using alpha factor
      extraction. MAIN RESEARCH VARIABLES: lung cancer stigma, depression, and quality
      of life. FINDINGS: four factors emerged: stigma and shame, social isolation,
      discrimination, and smoking. Inspection of unrotated first-factor loadings showed
      support for a general stigma factor. Construct validity was supported by
      relationships with related constructs: self-esteem, depression, social support,
      and social conflict. Coefficient alphas ranging from 0.75-0.97 for the subscales
      (0.96 for stigma and shame, 0.97 for social isolation, 0.9 for discrimination,
      and 0.75 for smoking) and 0.98 for the 43-item Cataldo Lung Cancer Stigma Scale
      (CLCSS) provided evidence of reliability. The final version of the CLCSS was 31
      items. Coefficient alpha was recalculated for the total stigma scale (0.96) and
      the four subscales (0.97 for stigma and shame, 0.96 for social isolation, 0.92
      for discrimination, and 0.75 for smoking). CONCLUSIONS: the CLCSS is a reliable
      and valid measure of health-related stigma in this sample of people with lung
      cancer. IMPLICATIONS FOR NURSING: the CLCSS can be used to identify the presence
      and impact of lung cancer stigma and allow for the development of effective
      stigma interventions for patients with lung cancer.

PMID- 21186152
TI  - Tailoring cancer education and support programs for low-income, primarily African
      American cancer survivors.
AB  - PURPOSE/OBJECTIVES: to identify the information and stress-management topics of
      most interest to low-income, predominantly African American cancer survivors.
      RESEARCH APPROACH: descriptive, cross sectional. SETTING: outpatient oncology
      clinic in a public hospital in Birmingham, Alabama. PARTICIPANTS: 25 patients
      with cancer; 12 were men, 22 were African Americans, and 16 had a 12th-grade
      education or less. METHODOLOGIC APPROACH: patients ranked potential topics to be
      included in an educational curriculum. MAIN RESEARCH VARIABLES: quantitative
      rankings of information and stress-management priorities. FINDINGS: learning
      about cancer, understanding cancer treatments, relieving cancer pain, and keeping
      well in mind and body were the most highly ranked topics among those offered
      within the American Cancer Society's I Can Cope curriculum, which also included
      supportive topics such as mobilizing social support. The preferred stress
      management topics were humor therapy, music therapy, meditation, and relaxation;
      lower-ranked topics included pet therapy and art as therapy. CONCLUSIONS: cancer
      survivors appear most interested in topics specific to their illness and
      treatment versus supportive topics. Stress management also received high
      rankings. INTERPRETATION: nurses have a key role in providing patient education
      and support. Tailoring education programs may better target specific needs and
      improve the quality of cancer care of underserved patients.

PMID- 21186153
TI  - Top 10 from the top two.

PMID- 21186155
TI  - The power of videotaped personal statements of patients with lung cancer: a
      recruitment strategy for smoking prevention and cessation programs.

PMID- 21186156
TI  - A young woman looks back: losing her mother to breast cancer.

PMID- 21186157
TI  - Determinants of quality of life in patients near the end of life: a longitudinal
      perspective.
AB  - PURPOSE/OBJECTIVES: to describe the quality of life (QOL) of patients near the
      end of life and to identify determinants of their QOL. DESIGN: descriptive,
      longitudinal. SETTING: university-affiliated cancer center, two private
      oncologists' offices, and patients' homes. SAMPLE: 80 patients with either stage
      IIIb or IV lung cancer newly diagnosed in the previous month or recurrent lung
      cancer with distant disease. METHODS: patients were interviewed for responses to
      instruments to assess demographic, physical, psychosocial, and spiritual
      characteristics. Baseline data were collected at the patients' places of oncology
      care. Home visits were made for the two-month and four-month data collection
      points. MAIN RESEARCH VARIABLES: QOL; symptom frequency, severity, and distress;
      functional status; anxiety; depression. FINDINGS: fifty percent of patients died
      within five months of their lung cancer diagnosis. Patients reported a relatively
      high QOL that did not change significantly as they approached the end of life.
      Symptom distress was the strongest determinant of QOL, followed by symptom
      severity, symptom frequency, and depression. CONCLUSIONS: QOL was most affected
      by symptoms experienced in patients with advanced lung cancer, particularly
      distress associated with symptoms. Interventions for symptom management must be
      implemented at diagnosis because patients in this population may approach the end
      of life quickly. IMPLICATIONS FOR NURSING: a routine and thorough symptom
      assessment is imperative for patients with advanced lung cancer. Attention to
      symptom distress is important because of its effect on QOL.

PMID- 21186158
TI  - Identification of latent classes in patients who are receiving biotherapy based
      on symptom experience and its effect on functional status and quality of life.
AB  - PURPOSE/OBJECTIVES: to identify subgroups of patients receiving biotherapy with
      pain, fatigue, sleep disturbance, and depression and to determine functional
      status and quality of life differences between subgroups. DESIGN: a descriptive,
      prospective, cohort study design. SETTING: internet-based survey. SAMPLE: 187
      patients with cancer receiving biotherapy. METHODS: pain intensity, Piper Fatigue
      Scale, General Sleep Disturbance Scale, Center for Epidemiological Studies
      Depression, Karnofsky Performance Scale, and the Multidimensional Quality of Life
      Scale-Cancer were used at two time points one month apart (T1 and T2). Latent
      profile analysis identified subgroups. MAIN RESEARCH VARIABLES: biotherapy,
      symptoms, functional status, and quality of life. FINDINGS: At T1 (N = 187), five
      patient subgroups were identified, ranging from subgroup 1 (mild fatigue and
      sleep disturbance) to subgroup 5 (severe on all four symptoms). At T2 (N = 114),
      three patient subgroups were identified, ranging from subgroup 1 (mild pain,
      fatigue, and sleep disturbance without depression) to subgroup 3 (mild pain,
      moderate fatigue, and sleep disturbance with severe depression). At each time
      point, the patient subgroup with the most severe symptoms showed significantly
      lower functional status and quality of life. CONCLUSIONS: as with other cancer
      treatments, biotherapy can be divided into similar patient subgroups with four
      prevalent symptoms. Subgroups of patients differ in functional status and quality
      of life as a result of symptom severity. IMPLICATIONS FOR NURSING: clinicians
      should assess and identify patients with severe levels of the four prevalent
      symptoms and offer appropriate interventions. Future study is needed to
      investigate the factors that contribute to symptom severity and to examine the
      occurrence of symptom clusters that may place patients at increased risk for
      poorer outcomes.

PMID- 21186159
TI  - A breast navigator program: barriers, enhancers, and nursing interventions.
AB  - PURPOSE/OBJECTIVES: to identify barriers to and enhancers of completion of breast
      cancer treatment from the perspective of participants in a breast health
      navigator program. RESEARCH APPROACH: qualitative, using focus group methodology
      and telephone interview. SETTING: two teaching hospital ambulatory cancer
      centers. PARTICIPANTS: women enrolled in the breast navigator program, including
      patients who completed (n = 13) and did not complete (n = 1) breast cancer
      treatment. METHODOLOGIC APPROACH: researchers used semistructured, open-ended
      questioning to guide the interviews and elicit identification of barriers to and
      enhancers of treatment. A flexible approach was used and the interviews were
      recorded. Content analysis was used to identify themes. MAIN RESEARCH VARIABLES:
      perceived barriers and enhancers of breast cancer treatment. FINDINGS: the most
      common theme was the value of the education and information received from the
      navigator. Several participants saw this as the essence of the role. Assistance
      with managing symptoms, access to financial and community resources, and the team
      approach were completion enhancers. CONCLUSIONS: completion of breast cancer
      therapy and care can be improved by recognizing the value the nurse navigator
      role brings to the patient experience and enhancing that role. INTERPRETATION:
      the intentional presence of the oncology nurse and the nursing emphasis on
      culturally appropriate education and care can be seen as key competencies of the
      navigator. As the concept of the navigation process is expanded to other cancers,
      oncology nurses are particularly well positioned to advocate for the navigator
      role as a nursing domain.

PMID- 21186160
TI  - Healthcare team members' perception of staffing adequacy in a comprehensive
      cancer center.
AB  - PURPOSE/OBJECTIVES: to describe the perceptions of staffing adequacy of
      healthcare team members working together on units in a comprehensive cancer
      center. RESEARCH APPROACH: a descriptive, phenomenologic design was used.
      Semistructured interviews were conducted with participants. SETTING: an urban,
      Magnet-designated comprehensive cancer center in the southwestern United States.
      PARTICIPANTS: a purposive sample of 10 RNs, 5 nursing assistants, and 5 associate
      directors. METHODOLOGIC APPROACH: data analysis was guided by Streubert's
      procedural interpretation of the phenomenologic method. FINDINGS: themes emerged,
      including alterations to care; challenges to an already challenging shift; the
      right mix; effects on patients, safety, and quality; mitigating factors; and the
      aftermath. CONCLUSIONS: perceived inadequate staffing affects healthcare staff
      both personally and professionally, triggering responses that influence
      approaches to patient care, unit operations, and relationships. INTERPRETATION:
      the unique and sometimes varied perspectives and experiences of frontline staff
      are critical to understanding factors that influence and affect willingness to
      work and remain in hospital settings, and may serve as a basis for shaping
      interventions and strategies to ensure adequate numbers of caregivers at the
      bedside.

PMID- 21186161
TI  - Depressive symptoms, grief, and complicated grief among family caregivers of
      patients with advanced cancer three months into bereavement.
AB  - PURPOSE/OBJECTIVES: to describe depressive symptoms, grief, and complicated grief
      for bereaved family caregivers of patients who died from cancer-related causes
      and to explore relationships among these variables. DESIGN: a nonexperimental,
      secondary analysis of cross-sectional descriptive data from a longitudinal
      intervention study evaluating the effect of providing feedback from standardized
      assessment tools. SETTING: two large, private, not-for-profit hospices in
      Florida. SAMPLE: convenience sample of 280 family caregivers, bereaved three
      months. METHODS: secondary analysis of self-report, survey data three months
      following death. MAIN RESEARCH VARIABLES: depressive symptoms, grief, and
      complicated grief. FINDINGS: Three months after the loss of a loved one, 34% of
      the caregivers had clinically meaningful scores for depressive symptoms. A
      significant number of bereaved caregivers were experiencing grief and depression.
      CONCLUSIONS: bereaved caregivers were experiencing significant levels of
      depressive symptoms and complicated grief. Caregivers with higher levels of grief
      had more depressive symptoms. IMPLICATIONS FOR NURSING: tools are available to
      identify bereaved caregivers most in need of intervention.

PMID- 21186162
TI  - Evaluation of tobacco cessation classes aimed at hospital staff nurses.
AB  - PURPOSE/OBJECTIVES: to evaluate a three-hour smoking cessation program and its
      effect on nurse knowledge, counseling behaviors, and confidence in counseling
      behaviors. DESIGN: program evaluation. SETTING: a Magnet-designated, 500-bed
      community hospital in Southern California. SAMPLE: 107 nurses. METHODS: program
      content included behavior counseling and pharmacotherapy along with role playing.
      Investigator-developed self-report surveys were completed on the day of the class
      and at 3, 6, and 12 months. MAIN RESEARCH VARIABLES: Short- and long-term changes
      in nurse knowledge, attitudes, and behaviors about tobacco cessation efforts.
      FINDINGS: knowledge significantly increased from baseline to post-test.
      Counseling skills improved. Nurses who completed all surveys exhibited no
      significant changes about asking patients to quit smoking but did demonstrate
      significant changes at three months regarding advising patients, assessing quit
      readiness, and providing assistance. Changes were maintained over the year.
      Nurses' average ability to counsel patients was rated "good or very good" after
      one year. At 3, 6, and 12 months, most respondents reported providing cessation
      counseling or referrals to at least one patient. CONCLUSIONS: these findings
      support tobacco cessation programs for bedside nurses as useful in enhancing
      nurse confidence in patient-counseling skills. IMPLICATIONS FOR NURSING: study
      findings demonstrated benefits to using the developed curriculum. Additional
      research is needed on tobacco cessation programs for hospital nurses,
      particularly with longitudinal outcomes and actual nurse behaviors.

PMID- 21186163
TI  - A pilot study of activity engagement in the first six months after stem cell
      transplantation.
AB  - PRPOSE/OBJECTIVES: to describe the natural pace and pattern of activity
      resumption in the first six months after stem cell transplantation (SCT). DESIGN:
      longitudinal, descriptive survey. SETTING: bone marrow transplantation program of
      a National Cancer Institute-designated comprehensive cancer center in the
      northeastern United States. SAMPLE: 18 men and 18 women who underwent either
      autologous (83%) or allogeneic (17%) transplantation. METHODS: participants were
      surveyed 30 days, 100 days, and six months after SCT. Descriptive statistics were
      followed by exploratory linear mixed modeling with factors of time, gender, and
      the interaction between time and gender. MAIN RESEARCH VARIABLES: a modified
      checklist version of the Activity Card Sort was used to measure activity
      retention. FINDINGS: participants generally were performing 49% of their usual
      activities 30 days after transplantation, 70% of their premorbid activities 100
      days after transplantation, and 77% of their premorbid activities six months
      after transplantation. Level of activity engagement increased over time, with the
      greatest changes observed from 30-100 days after SCT. Men retained more of their
      activities than women in the domains of low physical-demand leisure and social
      activities. CONCLUSIONS: rehabilitation screening may be most helpful in the
      period from 100 days to six months, when activity levels begin to plateau.
      Activity recovery may differ for men and women; future research should explore
      how this could affect rehabilitation needs. IMPLICATIONS FOR NURSING: nurses can
      use structured surveys to explore and promote patients' satisfaction with and
      ability to engage in daily activities and ensure appropriate referrals to
      rehabilitation during recovery from SCT.

PMID- 21186164
TI  - The attitudes, communication, treatment, and support intervention to reduce
      breast cancer treatment disparity.
AB  - PURPOSE/OBJECTIVES: to test the effect of a supportive, one-time
      psychoeducational intervention on treatment adherence among African American
      women receiving first adjuvant therapy for breast cancer. DESIGN: a pilot,
      randomized, controlled clinical trial, two-group design, with one-time
      intervention and four data collection points. SETTING: two University of
      Pittsburgh Cancer Institute clinics. SAMPLE: 24 African American women. METHODS:
      the Attitudes, Communication, Treatment, and Support (ACTS) intervention is a 45
      minute one-on-one session with an African American woman recommended to have
      chemotherapy for breast cancer. The interventionist is an African American breast
      cancer survivor. The intervention consists of a discussion about chemotherapy and
      the importance of communicating knowledge needs and distress, an explanation of
      the specific treatment plan according to pathology, and support through the
      survivor testimonial and video clips from the African American community. MAIN
      RESEARCH VARIABLES: dose of chemotherapy received and dose of chemotherapy
      prescribed. FINDINGS: Twenty patients completed chemotherapy, and four chose not
      to begin or discontinued recommended chemotherapy. The groups were equal in key
      sociodemographic variables. Compared to usual care, the ACTS intervention
      participants demonstrated trends toward initiation of chemotherapy (100% versus
      82%), overall adherence to chemotherapy (92% versus 73%), and percentage of total
      dose of chemotherapy received or prescribed (94% versus 74%). Compared to usual
      care, the ACTS intervention participants demonstrated more rapid initiation of
      chemotherapy and better overall adherence to chemotherapy. CONCLUSIONS: the pilot
      ACTS intervention shows promise as a psychoeducational intervention to assist
      with chemotherapy decision making among African American women. IMPLICATIONS FOR
      NURSING: African American women are at high risk of not receiving the full dose
      of prescribed chemotherapy for breast cancer for multiple reasons. Nurses must be
      sensitive to the unique fears and concerns of this population regarding
      chemotherapy decisions. An intervention addressing these fears and concerns may
      help to increase adherence.

PMID- 21186167
TI  - One's motor performance predictably modulates the understanding of others'
      actions through adaptation of premotor visuo-motor neurons.
AB  - Neurons firing both during self and other's motor behavior (mirror neurons) have
      been described in the brain of vertebrates including humans. The activation of
      somatic motor programs driven by perceived behavior has been taken as evidence
      for mirror neurons' contribution to cognition. The inverse relation, that is the
      influence of motor behavior on perception, is needed for demonstrating the long
      hypothesized causal role of mirror neurons in action understanding. We provide
      here conclusive behavioral and neurophysiological evidence for that causal role
      by means of cross-modal adaptation coupled with a novel transcranial magnetic
      stimulation (TMS)-adaptation paradigm. Blindfolded repeated motor performance of
      an object-directed action (push or pull) induced in healthy participants a strong
      visual after-effect when categorizing others' actions, as a result of motor-to
      visual adaptation of visuo-motor neurons. TMS over the ventral premotor cortex,
      but not over the primary motor cortex, suppressed the after-effect, thus
      localizing the population of adapted visuo-motor neurons in the premotor cortex.
      These data are exquisitely consistent in humans with the existence of premotor
      mirror neurons that have access to the action meaning. We also show that
      controlled manipulation of the firing properties of this neural population
      produces strong predictable changes in the way we categorize others' actions.

PMID- 21186168
TI  - Association between SLC2A9 transporter gene variants and uric acid phenotypes in
      African American and white families.
AB  - OBJECTIVES: SLC2A9 gene variants associate with serum uric acid in white
      populations, but little is known about African American populations. Since SLC2A9
      is a transporter, gene variants may be expected to associate more closely with
      the fractional excretion of urate, a measure of renal tubular transport, than
      with serum uric acid, which is influenced by production and extrarenal clearance.
      METHODS: Genotypes of single nucleotide polymorphisms (SNPs) distributed across
      the SLC2A9 gene were obtained in the Genetic Epidemiology Network of Arteriopathy
      cohorts. The associations of SNPs with serum uric acid, fractional excretion of
      urate and urine urate-to-creatinine ratio were assessed with adjustments for age,
      sex, diuretic use, BMI, homocysteine and triglycerides. RESULTS: We identified
      SLC2A9 gene variants that were associated with serum uric acid in 1155 African
      American subjects (53 SNPs) and 1132 white subjects (63 SNPs). The most
      statistically significant SNPs in African American subjects (rs13113918) and
      white subjects (rs11723439) were in the latter half of the gene and explained 2.7
      and 2.8% of the variation in serum uric acid, respectively. After adjustment for
      this SNP in African Americans, 0.9% of the variation in serum uric acid was
      explained by an SNP (rs1568318) in the first half of the gene. Unexpectedly,
      SLC2A9 gene variants had stronger associations with serum uric acid than with
      fractional excretion of urate. CONCLUSIONS: These findings support two different
      loci by which SLC2A9 variants affect uric acid levels in African Americans and
      suggest SLC2A9 variants affect serum uric acid level via renal and extrarenal
      clearance.

PMID- 21186169
TI  - Patients with limited rheumatoid arthritis-related interstitial lung disease have
      a better prognosis than those with extensive disease.

PMID- 21186170
TI  - HLA-G and HLA-E in patients with juvenile idiopathic arthritis.
AB  - OBJECTIVE: To investigate the expression and release of HLA-G and HLA-E in JIA.
      METHODS: Soluble (s)HLA-G and HLA-E were measured in sera from 58 JIA patients
      and 54 healthy donors. Surface expression of HLA-G, HLA-E and immunoglobulin-like
      transcript (ILT)2 and ILT4, two receptors for HLA-G, was assessed on T, B cells
      and monocytes from peripheral blood (PB) and SF of 12 JIA patients and from PB of
      12 controls. RESULTS: Serum sHLA-G concentration was significantly lower in
      patients than in controls. Both sHLA-G and sHLA-E were detected in SF and sHLA-E
      concentration in SF was higher in extended oligoarticular/polyarticular than in
      limited oligoarticular JIA. Patients compared with controls showed: (i) down
      regulation of HLA-E and ILT2 expression on T cells; (ii) up-regulation of HLA-E
      expression on B cells and monocytes; and (iii) down-regulation of ILT4 expression
      on monocytes. Comparing JIA patients' SF and PB we found: (i) up-regulation of
      HLA-E and ILT2 expression in T and B cells and monocytes; and (ii) down
      regulation of ILT4 expression in monocytes. ILT4 was up-regulated in monocytes
      from oligoarticular extended/polyarticular compared with oligoarticular limited
      JIA. CONCLUSIONS: A lower concentration of sHLA-G in sera may predispose to JIA,
      as observed for other autoimmune diseases. sHLA-E concentration in SF correlate
      with the number of affected joints. Higher ILT2 expression on SF cell populations
      compared with PB may be related to high sHLA-G concentration in SF. Higher HLA-E
      expression in SF than in PB cell populations may protect them from NK cytolysis.

PMID- 21186171
TI  - Therapeutic effects of TACI-Ig on rats with adjuvant-induced arthritis via
      attenuating inflammatory responses.
AB  - OBJECTIVE: To investigate the effects of TACI-Ig, a recombinant fusion protein
      that modulates B- and T-cell activation by binding and neutralizing B-lymphocyte
      stimulator (BLyS) and a proliferation-inducing ligand (APRIL), in an established
      adjuvant-induced arthritis (AA) rat model. METHODS: Rats with experimental
      arthritis were randomly separated into different groups and then treated with
      TACI-Ig (0.7, 2.1, 6.3 mg/kg), rhTNFR-Fc (2.8 mg/kg), MTX (0.5 mg/kg) or IgG-Fc
      (6.3 mg/kg), from Day 16 to Day 34 after immunization. Arthritis was evaluated by
      hind paw swelling, polyarthritis index and histopathological examination.
      Activities of BLyS, APRIL, IL-1beta, IL-2, IL-10, TGF-beta1, PGE(2), TNF-alpha,
      IFN-gamma, immunoglobulin (Ig)G1, IgG2a, IgM and IgA were assessed by ELISA.
      Cluster of differentiation (CD)20 expression was detected by immunohistochemical
      analysis. RESULTS: TACI-Ig (2.1, 6.3 mg/kg) treatment significantly reduced the
      severity of established arthritis using the methods of clinical observation and
      histopathological examination. TACI-Ig treatment inhibited expression of IgM,
      decreased the expression of BLyS and APRIL and regulated the balance of pro
      inflammatory and anti-inflammatory cytokines in serum of AA rats.
      Immunohistochemical analysis demonstrated that CD20 production was reduced in
      spleen. CONCLUSIONS: Data presented here demonstrate that administration of TACI
      Ig significantly attenuates progression of experimental arthritis, with
      reductions in inflammatory response and bone and joint destruction.

PMID- 21186172
TI  - The power Doppler ultrasonography score from 24 synovial sites or 6 simplified
      synovial sites, including the metacarpophalangeal joints, reflects the clinical
      disease activity and level of serum biomarkers in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: We evaluated the significance of the power Doppler ultrasonography
      (PDUS) score by comparing it with serum biomarkers and clinical disease activity.
      METHODS: We measured the PDUS scores of 24 synovial sites in 12 joints in 22 RA
      patients. For convenience, the PDUS scores of six synovial sites in six joints
      were also examined. Each joint was scored for a power Doppler (PD) signal on a
      scale from 0 to 3. The PDUS scores are the sums of the PD signal scores for the
      24 synovial sites or the 6 synovial sites. On the same day, serum variables as
      well as clinical disease activity were evaluated. RESULTS: The PDUS scores from
      the 24 joint sites were significantly positively correlated with DAS of 28 joints
      (DAS-28), simplified disease activity index (SDAI), clinical disease activity
      index (CDAI) and serum biomarkers including MMP-3, VEGF and tissue inhibitor of
      metalloproteinases-1 (TIMP-1). Accordingly, the PDUS scores from the six synovial
      sites greatly correlated with those from the 24 joint sites. Clinical disease
      activities as well as serum variables were also clearly correlated with the PDUS
      scores from the six synovial sites. CONCLUSION: The standard as well as the
      simplified PDUS scores well reflected clinical disease activity and serum
      variables, including angiogenic factors. Our data reaffirm the utility of
      ultrasonography for monitoring disease activity in patients with RA.

PMID- 21186173
TI  - Peach (Prunus persica) fruit response to anoxia: reversible ripening delay and
      biochemical changes.
AB  - The use of modified atmospheres has been successfully applied in different fruits
      to delay the ripening process and to prevent physiological disorders. In
      addition, during normal ripening, hypoxic areas are generated inside the fruit;
      moreover, anaerobic conditions may also arise during fruit post-harvest storage
      and handling. In consequence, the fruit is an interesting model to analyze the
      metabolic modifications due to changes in oxygen levels. In this work, a 72 h
      anoxic treatment by using an N(2) storage atmosphere was applied to peaches
      (Prunus persica L. Batsch) after harvest. Ripening was effectively delayed in
      treated fruits, preventing fruit softening, color changes and ethylene
      production. Metabolic changes induced by anoxia included induction of
      fermentative pathways, glycolysis and enzymes involved in both sucrose synthesis
      and degradation. Sucrose, fructose and glucose contents remained unchanged in
      treated fruit, probably due to sucrose cycling. Sorbitol was not consumed and
      citrate was increased, correlating with citric acid cycle impairment due to O(2)
      deprivation. Malate content was not affected, indicating compensation in the
      reactions producing and consuming malate. Changes in malic enzymes and pyruvate
      orthophosphate dikinase may provide pyruvate for fermentation or even act to
      regenerate NADP. After fruit transfer to aerobic conditions, no signs of post
      anoxia injury were observed and metabolic changes were reversed, with the
      exception of acetaldehyde levels. The results obtained indicate that peach fruit
      is an organ with a high capacity for anoxic tolerance, which is in accord with
      the presence of hypoxic areas inside fruits and the fact that hypoxic pre
      treatment improves tolerance to subsequent anoxia.

PMID- 21186174
TI  - The circadian clock modulates water dynamics and aquaporin expression in
      Arabidopsis roots.
AB  - We have developed a plant growth system to analyze water dynamics in the roots of
      a small model plant, Arabidopsis thaliana, by nuclear magnetic resonance (NMR)
      microscopic imaging. Using the two-dimensional slice technique, we obtained a
      series of images with high signal-to-noise ratio indicating the water
      distribution in the root. To demonstrate light regulation of water transport in
      the root and involvement of aquaporin gene expression, we visualized the
      distribution of water in Arabidopsis roots under various light conditions and
      compared the data with the expression profiles of two aquaporin genes. (1)H-NMR
      imaging revealed that water content in Arabidopsis roots is lower in the light
      than in the dark. This diurnal variation in water content was clearly observed in
      the basal zone of the root. In addition, an autonomous rhythm of water dynamics
      was observed under continuous light (LL) and darkness (DD). However, the
      circadian oscillation in water dynamics was obscured in the early-flowering 3
      (elf3) mutant under LL. The expression of both the aquaporin genes, AtPIP1;2 and
      AtPIP2;1, oscillated with the circadian rhythm under LL conditions in wild-type
      seedlings, but not in the elf3 mutant. These results demonstrate the advantages
      of our technique for monitoring water dynamics in roots of living Arabidopsis
      seedlings, and suggest that the circadian clock modulates water dynamics and
      aquaporin expression.

PMID- 21186175
TI  - OryzaExpress: an integrated database of gene expression networks and omics
      annotations in rice.
AB  - Similarity of gene expression profiles provides important clues for understanding
      the biological functions of genes, biological processes and metabolic pathways
      related to genes. A gene expression network (GEN) is an ideal choice to grasp
      such expression profile similarities among genes simultaneously. For GEN
      construction, the Pearson correlation coefficient (PCC) has been widely used as
      an index to evaluate the similarities of expression profiles for gene pairs.
      However, calculation of PCCs for all gene pairs requires large amounts of both
      time and computer resources. Based on correspondence analysis, we developed a new
      method for GEN construction, which takes minimal time even for large-scale
      expression data with general computational circumstances. Moreover, our method
      requires no prior parameters to remove sample redundancies in the data set. Using
      the new method, we constructed rice GENs from large-scale microarray data stored
      in a public database. We then collected and integrated various principal rice
      omics annotations in public and distinct databases. The integrated information
      contains annotations of genome, transcriptome and metabolic pathways. We thus
      developed the integrated database OryzaExpress for browsing GENs with an
      interactive and graphical viewer and principal omics annotations
      (http://riceball.lab.nig.ac.jp/oryzaexpress/). With integration of Arabidopsis
      GEN data from ATTED-II, OryzaExpress also allows us to compare GENs between rice
      and Arabidopsis. Thus, OryzaExpress is a comprehensive rice database that
      exploits powerful omics approaches from all perspectives in plant science and
      leads to systems biology.

PMID- 21186178
TI  - The risk of foot ulceration in people with diabetes screened in community
      settings: findings from a cohort study.
AB  - BACKGROUND: Annual foot checks are recommended in patients with diabetes mellitus
      (DM) to identify those at risk of foot ulceration. Systematic reviews have found
      few studies evaluating the predictive value of tests in community-based diabetic
      populations. AIM: To quantify the predictive value of clinical risk factors in
      relation to foot ulceration in a community population. METHODS: A cohort of 1192
      people with diabetes receiving care in community settings was recruited and a
      screening procedure, covering symptoms, signs and diagnostic tests was conducted
      at baseline. At an average 1-year follow-up patients who developed a foot ulcer
      were identified by an independent blind assessor. Multivariable analysis was
      performed to identify clinical predictors of foot ulceration. FINDINGS: The
      incidence of foot ulceration was 1.93% [95% confidence interval (CI) 1.27-2.89).
      Three time-independent clinical predictors with five factors were selected:
      previous amputation [odds ratio (OR) 14.7, 95% CI 3.1-69.5), use of insulin
      before 3 months with inability to distinguish between cool and cold temperatures
      (OR 2.97, 95% CI 1.9-4.5) and failure to obtain at least one blood pressure
      reading for the calculation of ankle-brachial index with the failure to feel
      touch with a 10-g monofilament (OR 1.7, 95% CI 1.3-2.2). INTERPRETATION:
      Recommendations for annual diabetic foot check in low-risk, community-based
      patients should be reviewed as absolute events of ulceration are low. The
      accuracy of foot risk assessment tools to predict ulceration requires evaluation
      in randomized controlled trials with concurrent economic evaluations.

PMID- 21186176
TI  - RiceFOX: a database of Arabidopsis mutant lines overexpressing rice full-length
      cDNA that contains a wide range of trait information to facilitate analysis of
      gene function.
AB  - Identification of gene function is important not only for basic research but also
      for applied science, especially with regard to improvements in crop production.
      For rapid and efficient elucidation of useful traits, we developed a system named
      FOX hunting (Full-length cDNA Over-eXpressor gene hunting) using full-length
      cDNAs (fl-cDNAs). A heterologous expression approach provides a solution for the
      high-throughput characterization of gene functions in agricultural plant species.
      Since fl-cDNAs contain all the information of functional mRNAs and proteins, we
      introduced rice fl-cDNAs into Arabidopsis plants for systematic gain-of-function
      mutation. We generated >30,000 independent Arabidopsis transgenic lines
      expressing rice fl-cDNAs (rice FOX Arabidopsis mutant lines). These rice FOX
      Arabidopsis lines were screened systematically for various criteria such as
      morphology, photosynthesis, UV resistance, element composition, plant hormone
      profile, metabolite profile/fingerprinting, bacterial resistance, and heat and
      salt tolerance. The information obtained from these screenings was compiled into
      a database named 'RiceFOX'. This database contains around 18,000 records of rice
      FOX Arabidopsis lines and allows users to search against all the observed
      results, ranging from morphological to invisible traits. The number of searchable
      items is approximately 100; moreover, the rice FOX Arabidopsis lines can be
      searched by rice and Arabidopsis gene/protein identifiers, sequence similarity to
      the introduced rice fl-cDNA and traits. The RiceFOX database is available at
      http://ricefox.psc.riken.jp/.

PMID- 21186179
TI  - A complicated pelvic fracture in an octogenarian.

PMID- 21186177
TI  - Epigenetic reprogramming and development: a unique heterochromatin organization
      in the preimplantation mouse embryo.
AB  - Fertilization of the oocyte by the sperm results in the formation of a totipotent
      zygote, in which the maternal and paternal chromatin is enclosed in two pronuclei
      undergoing distinct programmes of transcriptional activation and chromatin
      remodelling. The highly packaged paternal chromatin delivered by the sperm is
      decondensed and acquires a number of specific epigenetic marks, but markedly
      remains devoid of those usually associated with constitutive heterochromatin.
      During this period the maternal chromatin remains relatively stable except for
      marks associated with transcription and/or replication such as arginine
      methylation and H3/H4 acetylation. The embryo then undergoes a series of mitotic
      divisions without significant additional growth but differentiation, resulting in
      the formation of a blastocyst containing distinct cell types. The chromatin
      remodelling events during these stages are likely to be important in establishing
      the nuclear foundations required for later triggers of differentiation. Overall,
      we summarize three important points during these earliest reprogramming events:
      (i) relatively stable maternal chromatin after fertilization, (ii) rapid
      acquisition of specific histone marks by the paternal chromatin during the hours
      that follow fertilization and (iii) rapid remodelling of constitutive
      heterochromatic marks and modifications in the core of the nucleosome from the
      first mitotic division. These features are likely to be required for the creation
      of a chromatin environment compatible with cellular reprogramming and plasticity.

PMID- 21186180
TI  - Histiocytic sarcoma of the central nervous system: a challenging diagnosis.

PMID- 21186182
TI  - The annotation and the usage of scientific databases could be improved with
      public issue tracker software.
AB  - Since the publication of their longtime predecessor The Atlas of Protein
      Sequences and Structures in 1965 by Margaret Dayhoff, scientific databases have
      become a key factor in the organization of modern science. All the information
      and knowledge described in the novel scientific literature is translated into
      entries in many different scientific databases, making it possible to obtain very
      accurate information on a biological entity like genes or proteins without having
      to manually review the literature on it. However, even for the databases with the
      finest annotation procedures, errors or unclear parts sometimes appear in the
      publicly released version and influence the research of unaware scientists using
      them. The researcher that finds an error in a database is often left in a
      uncertain state, and often abandons the effort of reporting it because of a lack
      of a standard procedure to do so. In the present work, we propose that the simple
      adoption of a public error tracker application, as in many open software
      projects, could improve the quality of the annotations in many databases and
      encourage feedback from the scientific community on the data annotated publicly.
      In order to illustrate the situation, we describe a series of errors that we
      found and helped solve on the genes of a very well-known pathway in various
      biomedically relevant databases. We would like to show that, even if a majority
      of the most important scientific databases have procedures for reporting errors,
      these are usually not publicly visible, making the process of reporting errors
      time consuming and not useful. Also, the effort made by the user that reports the
      error often goes unacknowledged, putting him in a discouraging position.

PMID- 21186183
TI  - A proposed method of bias adjustment for meta-analyses of published observational
      studies.
AB  - OBJECTIVE: Interpretation of meta-analyses of published observational studies is
      problematic because of numerous sources of bias. We develop bias assessment,
      elicitation and adjustment methods, and apply them to a systematic review of
      longitudinal observational studies of the relationship between objectively
      measured physical activity and subsequent change in adiposity in children.
      METHODS: We separated internal biases that reflect study quality from external
      biases that reflect generalizability to a target setting. Since published results
      were presented in different formats, these were all converted to correlation
      coefficients. Biases were considered as additive or proportional on the
      correlation scale. Opinions about the extent of each bias in each study, together
      with its uncertainty, were elicited in a formal process from quantitatively
      trained assessors for the internal biases and subject-matter specialists for the
      external biases. Bias-adjusted results for each study were combined across
      assessors using median pooling, and results combined across studies by random
      effects meta-analysis. RESULTS: Before adjusting for bias, the pooled correlation
      is difficult to interpret because the studies varied substantially in quality and
      design, and there was considerable heterogeneity. After adjusting for both the
      internal and external biases, the pooled correlation provides a meaningful
      quantitative summary of all available evidence, and the confidence interval
      incorporates the elicited uncertainties about the extent of the biases. In the
      adjusted meta-analysis, there was no apparent heterogeneity. CONCLUSION: This
      approach provides a viable method of bias adjustment for meta-analyses of
      observational studies, allowing the quantitative synthesis of evidence from
      otherwise incompatible studies. From the meta-analysis of longitudinal
      observational studies, we conclude that there is no evidence that physical
      activity is associated with gain in body fat.

PMID- 21186184
TI  - Commentary: testosterone and the metabolic syndrome: cause or consequence?

PMID- 21186185
TI  - ATP independent type IB topoisomerase of Leishmania donovani is stimulated by
      ATP: an insight into the functional mechanism.
AB  - Most type IB topoisomerases do not require ATP and Mg(2+) for activity. However,
      as shown previously for vaccinia topoisomerase I, we demonstrate that ATP
      stimulates the relaxation activity of the unusual heterodimeric type IB
      topoisomerase from Leishmania donovani (LdTOP1L/S) in the absence of Mg(2+). The
      stimulation is independent of ATP hydrolysis but requires salt as a co-activator.
      ATP binds to LdTOP1L/S and increases its rate of strand rotation. Docking studies
      indicate that the amino acid residues His93, Tyr95, Arg188 and Arg190 of the
      large subunit may be involved in ATP binding. Site directed mutagenesis of these
      four residues individually to alanine and subsequent relaxation assays reveal
      that the R190A mutant topoisomerase is unable to exhibit ATP-mediated stimulation
      in the absence of Mg(2+). However, the ATP-independent relaxation activities of
      all the four mutant enzymes remain unaffected. Additionally, we provide evidence
      that ATP binds LdTOP1L/S and modulates the activity of the otherwise ATP
      independent enzyme. This study establishes ATP as an activator of LdTOP1L/S in
      the absence of Mg(2+).

PMID- 21186186
TI  - The relationship between HIV-1 genome RNA dimerization, virion maturation and
      infectivity.
AB  - The relationship between virion protein maturation and genomic RNA dimerization
      of human immunodeficiency virus type 1 (HIV-1) remains incompletely understood.
      We have constructed HIV-1 Gag cleavage site mutants to enable the steady state
      observation of virion maturation steps, and precisely study Gag processing, RNA
      dimerization, virion morphology and infectivity. Within the virion maturation
      process, the RNA dimer stabilization begins during the primary cleavage (p2-NC)
      of Pr55 Gag. However, the primary cleavage alone is not sufficient, and the
      ensuing cleavages are required for the completion of dimerization. From our
      observations, the increase of cleavage products may not put a threshold on the
      transition from fragile to stable dimeric RNA. Most of the RNA dimerization
      process did not require viral core formation, and particle morphology dynamics
      during viral maturation did not completely synchronize with the transition of
      dimeric RNA status. Although the endogenous virion RT activity was fully acquired
      at the initial step of maturation, the following process was necessary for viral
      DNA production in infected cell, suggesting the maturation of viral RNA/protein
      plays critical role for viral infectivity other than RT process.

PMID- 21186187
TI  - Prevalence and regional differences of gestational diabetes mellitus and oral
      glucose tolerance tests in Finland.
AB  - BACKGROUND: The prevalence of gestational diabetes (GDM) is constantly increasing
      all around the world. Aim of this study is to report prevalence and regional
      differences of GDM, oral glucose tolerance tests (OGTT) and register-based GDM
      risk factors [age and body mass index (BMI)] among Finnish women. METHODS: Data
      from the Finnish Medical Birth Register including all deliveries in Finland
      during 2004-06 (N = 174 634) were used. The criteria for GDM were abnormal
      results in OGTT, GDM diagnosis based on ICD-10 classification or use of insulin
      treatment during pregnancy. Pregnant women with type I diabetes were excluded,
      but women with pregestational diabetes (type II) were included since they also
      can receive GDM diagnosis. RESULTS: The prevalence of GDM was 10-11% and OGTTs 22
      28% between the period 2004 until 2006. Regional differences were 2-fold both in
      prevalence of GDM (8-15%) and OGTTs (19-34%). Proportions of obese women varied
      between 28% and 35% and women aged >40 years between 3% and 4%. The regional
      differences in GDM prevalence were not attenuated when risk factors were taken
      into account. Overweight and age >=years explained only a fourth of the variation
      in GDM prevalence. CONCLUSION: Proportion of women undergoing OGTT increased but
      the prevalence of GDM did not during the study period. Two-fold regional
      differences in OGTT prevalence explained higher proportion of variation in
      prevalence of GDM than risk factors available from birth registry, age and BMI.

PMID- 21186188
TI  - Leadership, infrastructure and capacity to support child injury prevention: can
      these concepts help explain differences in injury mortality rankings between 18
      countries in Europe?
AB  - BACKGROUND: Mortality and morbidity rates, traditionally used indicators for
      child injury, are limited in their ability to explain differences in child injury
      between countries, are inadequate in capturing actions to address the problem of
      child injury and do not adequately identify progress made within countries. There
      is a need for a broader set of indicators to help better understand the success
      of countries with low rates of child injury, provide guidance and benchmarks for
      policy makers looking to make investments to reduce their rates of fatal and non
      fatal child injury and allow monitoring of progress towards achieving these
      goals. This article describes an assessment of national leadership,
      infrastructure and capacity in the context of child injury prevention in 18
      countries in Europe and explores the potential of these to be used as additional
      indicators to support child injury prevention practice. METHODS: Partners in 18
      countries coordinated data collection on 21 items relating to leadership,
      infrastructure and capacity. Responses were coded into an overall score and
      scores for each of the three areas and were compared with child injury mortality
      rankings using Spearman's rank correlation. RESULTS: Overall score and scores for
      leadership and capacity were significantly negatively correlated to child injury
      mortality ranking. CONCLUSIONS: Findings of this preliminary work suggest that
      these three policy areas may provide important guidance for the types of
      commitments that are needed in the policy arena to support advances in child
      safety and their assessment a way to measure progress.

PMID- 21186190
TI  - A test for heterotachy using multiple pairs of sequences.
AB  - Heterotachy is a general term to describe positions that evolve at different
      rates in different lineages. Heterotachy also can generally be viewed as
      multivariate rates-across-sites variation, which can be described as randomly
      drawing rates (or branch lengths) from a multivariate distribution for each
      branch at each site (Wu J, Susko E. 2009. General heterotachy and distance method
      adjustments. Mol Biol Evol. 26:2689-2697). Motivated by this result, we propose
      three new distance-based tests: a heterogeneity test, a heterotachy test, and a
      within-gene heterotachy test and demonstrate with simulations that they perform
      well under a wide range of conditions. We also applied the first two tests to two
      real data sets and found that although all these data sets showed significant
      evidence of heterotachy, there were subtrees for which the data were consistent
      with an equal rates or rates-across-sites model.heterogeneity, heterotachy,
      within-gene heterotachy, covarion model, distance method, hypothesis test.

PMID- 21186189
TI  - Extraordinary sequence divergence at Tsga8, an X-linked gene involved in mouse
      spermiogenesis.
AB  - The X chromosome plays an important role in both adaptive evolution and
      speciation. We used a molecular evolutionary screen of X-linked genes potentially
      involved in reproductive isolation in mice to identify putative targets of
      recurrent positive selection. We then sequenced five very rapidly evolving genes
      within and between several closely related species of mice in the genus Mus. All
      five genes were involved in male reproduction and four of the genes showed
      evidence of recurrent positive selection. The most remarkable evolutionary
      patterns were found at Testis-specific gene a8 (Tsga8), a spermatogenesis
      specific gene expressed during postmeiotic chromatin condensation and nuclear
      transformation. Tsga8 was characterized by extremely high levels of insertion
      deletion variation of an alanine-rich repetitive motif in natural populations of
      Mus domesticus and M. musculus, differing in length from the reference mouse
      genome by up to 89 amino acids (27% of the total protein length). This population
      level variation was coupled with striking divergence in protein sequence and
      length between closely related mouse species. Although no clear orthologs had
      previously been described for Tsga8 in other mammalian species, we have
      identified a highly divergent hypothetical gene on the rat X chromosome that
      shares clear orthology with the 5' and 3' ends of Tsga8. Further inspection of
      this ortholog verified that it is expressed in rat testis and shares remarkable
      similarity with mouse Tsga8 across several general features of the protein
      sequence despite no conservation of nucleotide sequence across over 60% of the
      rat-coding domain. Overall, Tsga8 appears to be one of the most rapidly evolving
      genes to have been described in rodents. We discuss the potential evolutionary
      causes and functional implications of this extraordinary divergence and the
      possible contribution of Tsga8 and the other four genes we examined to
      reproductive isolation in mice.

PMID- 21186191
TI  - The solute carrier families have a remarkably long evolutionary history with the
      majority of the human families present before divergence of Bilaterian species.
AB  - The Solute Carriers (SLCs) are membrane proteins that regulate transport of many
      types of substances over the cell membrane. The SLCs are found in at least 46
      gene families in the human genome. Here, we performed the first evolutionary
      analysis of the entire SLC family based on whole genome sequences. We
      systematically mined and analyzed the genomes of 17 species to identify SLC
      genes. In all, we identified 4,813 SLC sequences in these genomes, and we
      delineated the evolutionary history of each of the subgroups. Moreover, we also
      identified ten new human sequences not previously classified as SLCs, which most
      likely belong to the SLC family. We found that 43 of the 46 SLC families found in
      Homo sapiens were also found in Caenorhabditis elegans, whereas 42 of them were
      also found in insects. Mammals have a higher number of SLC genes in most
      families, perhaps reflecting important roles for these in central nervous system
      functions. This study provides a systematic analysis of the evolutionary history
      of the SLC families in Eukaryotes showing that the SLC superfamily is ancient
      with multiple branches that were present before early divergence of Bilateria.
      The results provide foundation for overall classification of SLC genes and are
      valuable for annotation and prediction of substrates for the many SLCs that have
      not been tested in experimental transport assays.

PMID- 21186192
TI  - Comment on: A potential role for daptomycin in enterococcal infections: what is
      the evidence?

PMID- 21186193
TI  - Activity of moxifloxacin against intracellular community-acquired methicillin
      resistant Staphylococcus aureus: comparison with clindamycin, linezolid and co
      trimoxazole and attempt at defining an intracellular susceptibility breakpoint.
AB  - BACKGROUND: Co-trimoxazole, clindamycin and linezolid are used to treat community
      acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, but
      little is known about intracellular activity. Moxifloxacin is active against
      intracellular methicillin-susceptible S. aureus (MSSA), but CA-MRSA has not been
      studied. METHODS: We used 12 clinical CA-MRSA, 1 MSSA overexpressing norA and 2
      hospital-acquired MRSA (moxifloxacin MICs: 0.03 to 4 mg/L). Activity was assessed
      in broth and after phagocytosis by THP-1 macrophages or keratinocytes
      {concentration-dependent experiments [24 h of incubation] to determine relative
      potencies [EC(50)], static concentrations [C(s)] and maximal relative efficacies
      [E(max) (change in log(10) cfu compared with initial inoculum)] and time
      dependent experiments [0-72 h] at human C(max)}. RESULTS: Concentration-dependent
      experiments: in broth, EC(50) and C(s) were correlated with the MIC for all
      antibiotics, but moxifloxacin achieved significantly (P < 0.01) greater killing
      (more negative E(max)) than the comparators; and in THP-1 cells and
      keratinocytes, moxifloxacin acted more slowly but still reached a near
      bactericidal effect (2 to 3 log(10) cfu decrease) at 24 h with unchanged EC(50)
      and C(s) as long as its MIC was <=0.125 mg/L (recursive partitioning analysis).
      Clindamycin and linezolid were static, and co-trimoxazole was unable to suppress
      the intracellular growth of CA-MRSA. At human C(max) in broth, moxifloxacin
      killed more rapidly and more extensively (>=5 log(10) cfu decrease at 10 h) than
      clindamycin (4 log(10) cfu at 48 h) or co-trimoxazole and linezolid (1-2 log(10)
      cfu at 72 h). CONCLUSIONS: Moxifloxacin is active against both extracellular and
      intracellular CA-MRSA if the MIC is low, and is more effective than clindamycin,
      co-trimoxazole and linezolid.

PMID- 21186195
TI  - Cystic lesions of the pancreas: current trends in approach and management.
AB  - The more frequent deployment of cross-sectional imaging for various abdominal
      conditions has resulted in an increased detection of cystic pancreatic lesions,
      particularly cystic pancreatic neoplasms. Cystic pancreatic lesions may be
      neoplastic or non-neoplastic. They may appear radiologically similar and often
      present a diagnostic dilemma; they need to be diagnosed and differentiated with
      accuracy in order to offer optimum treatment. Some of the cystic neoplasms are
      potentially malignant and have a wide spectrum of histological variation from the
      frankly benign 'adenomas' to invasive adenocarcinomas .When identified, these
      cystic lesions need a systematic work up and a diagnostic algorithm should be
      followed to its logical conclusion. This article reviews these cystic lesions of
      the pancreas, neoplastic and pseudocysts, and aims to update readers with the
      current trends in their diagnosis and management.

PMID- 21186194
TI  - Chemical modification of capuramycins to enhance antibacterial activity.
AB  - OBJECTIVES: To extend capuramycin spectrum of activity beyond mycobacteria and
      improve intracellular drug activity. METHODS: Three capuramycin analogues (SQ997,
      SQ922 and SQ641) were conjugated with different natural and unnatural amino acids
      or decanoic acid (DEC) through an ester bond at one or more available hydroxyl
      groups. In vitro activity of the modified compounds was determined against
      Mycobacterium spp. and representative Gram-positive and Gram-negative bacteria.
      Intracellular activity was evaluated in J774A.1 mouse macrophages infected with
      Mycobacterium tuberculosis (H37Rv). RESULTS: Acylation of SQ997 and SQ641 with
      amino undecanoic acid (AUA) improved in vitro activity against most of the
      bacteria tested. Conjugation of SQ922 with DEC, but not AUA, improved its
      activity against Gram-positive bacteria. In the presence of efflux pump inhibitor
      phenylalanine arginine beta-naphthyl amide, MICs of SQ997-AUA, SQ641-AUA and
      SQ922-DEC compounds improved even further against drug-susceptible and drug
      resistant Staphylococcus aureus. In Gram-negative bacteria, EDTA-mediated
      permeabilization caused 4- to 16-fold enhancement of the activity of AUA
      conjugated SQ997, SQ922 and SQ641. Conjugation of all three capuramycin analogues
      with AUA improved intracellular killing of H37Rv in murine macrophages.
      CONCLUSIONS: Conjugation of capuramycin analogues with AUA or DEC enhanced in
      vitro activity, extended the spectrum of activity in Gram-positive bacteria and
      increased intracellular activity against H37Rv.

PMID- 21186196
TI  - The value of a liaison neurology service in a district general hospital.
AB  - BACKGROUND: Healthcare development in the UK has resulted in an increase in
      neurologists working in district general hospitals. METHODS: The aim of the study
      was to determine the use of a neurologist for inpatient diagnosis and management,
      and to measure a neurologist's diagnostic reliability in a district general
      hospital over a 27-month period. Patient data were prospectively recorded. Follow
      up was performed independently by two clinicians reviewing the medical notes.
      Reasons for diagnostic change were determined. RESULTS: 306 inpatients were
      referred to the neurologist between 1 January 2007 and 31 March 2009 (2% of
      medical admissions). Mean (SD) age was 49.3 (18.8) years, and the female/male
      ratio was 1.2:1. Epilepsy and stroke were the most common diagnoses. Diagnostic
      concordance between referring physician and neurologist ranged from kappa score
      0.13 (spinal pathology) to 0.83 (central nervous system infection). Neurological
      opinion resulted in diagnostic change in 38.2% and management change in 88.8%.
      Only 1.6% of patients remained without a diagnosis, a fourfold improvement from
      physician referral. After medical records had been reviewed, 3.3% of inpatient
      diagnoses (10 of 306 patients) changed from the original diagnosis by the
      neurologist. Specialist investigation helped in revising diagnoses in four of the
      10 diagnostic changes. CONCLUSION: This study shows that in a district general
      hospital a neurologist can contribute to inpatient diagnosis and management with
      minimal diagnostic change over time, suggesting reliability of this service.

PMID- 21186197
TI  - Thoracic imaging findings in a case of disseminated cysticercosis.

PMID- 21186198
TI  - Patients' supportive care needs and psychological distress in advanced breast
      cancer patients in Japan.
AB  - OBJECTIVE: Few studies have investigated the prevalence of the unmet needs among
      advanced or recurrent breast cancer patients in Asian countries and little is
      known about the relation between their unmet needs and psychological
      distress/quality of life. METHODS: The participants (n = 87) comprised randomly
      selected ambulatory female patients with advanced or recurrent breast cancer
      attending the Outpatient Department of Oncology, Immunology and Surgery of Nagoya
      City University Hospital. The patients were asked to complete self-administered
      questionnaires assessing the level of their physical and psychological symptoms,
      supportive care needs and socio-demographic and biomedical factors. The
      association between the patients' perceived needs and psychological
      distress/quality of life was then analyzed statistically. RESULTS: The patients
      had a mean +/- standard deviation of 11 +/- 7.7 and a median of 10 unmet needs.
      The prevalence of the 17 most frequent unmet needs was over 50%, and almost all
      of these unmet need items belonged to the Psychological or the Health system and
      information domain. The total Short-form Supportive Care Needs Survey
      Questionnaire with cancer score was significantly associated with the indices of
      psychological distress and quality of life. Most of the Short-form Supportive
      Care Needs Survey Questionnaire with cancer domains except Sexuality domain were
      also significantly associated with all the indices of psychological distress.
      CONCLUSIONS: Psychosocial needs were strongly associated with psychological
      distress and quality of life. Quality of life and psychological distress may be
      improved if interventions for unmet needs, especially psychological and
      information needs, are made.

PMID- 21186199
TI  - Right coronary artery fistula to the coronary sinus and right atrium associated
      with giant right coronary enlargement detected by transthoracic echocardiography.
AB  - We present the case of a 54-year-old female with a previous history of lung
      fibrosis secondary to methotrexate used for rheumatoid arthritis who was referred
      to cardiology evaluation due to precordial pain. Echocardiography showed biatrial
      enlargement with an enlarged coronary sinus and tubular image posterior to the
      heart. On the coronary angiogram, the right coronary artery was enlarged, and a
      distal fistula was identified. The patient underwent a contrast enhanced cardiac
      computed tomography which demonstrated an aneurysmatic right coronary artery with
      a distal fistula to the right atrium and coronary sinus. As the chest pain did
      not recur and there was a high risk of the intervention to correct coronary
      fistula, the patient remained on conservative treatment.

PMID- 21186200
TI  - A conventional multimodality imaging cascade to detect a superior vena cava
      obstruction.
AB  - Iatrogenic injuries of the superior vena cava (SVC) following surgical or
      endovascular treatments are rare but challenging complications and require prompt
      diagnosis and appropriate treatment. The additional diagnostic value of
      venography, contrast-enhanced computed tomography, and magnetic resonance imaging
      has been widely assessed in the clinical setting of the SVC obstruction, whereas
      the role of conventional transoesophageal echocardiography (TEE) is still
      uncertain. A 43-year-old female patient was admitted to the echocardiography
      laboratory because of a superior vena cava syndrome (SVCS) following a balloon
      SVC venoplasty with stent implantation. A standard transoesophageal
      echocardiography examination clearly detected the SVC obstruction on previously
      implanted stents. We found that fundamental steps of early diagnosis of SVCS
      would benefit from standard TEE.

PMID- 21186201
TI  - HLA class II DPB1 and DRB1 polymorphisms associated with genetic susceptibility
      to beryllium toxicity.
AB  - OBJECTIVES: Chronic beryllium disease (CBD) is a hypersensitivity granulomatous
      pulmonary disease caused by exposure to the metal beryllium (Be2+). Our objective
      was to extend current knowledge of the genetics of beryllium disease by examining
      all HLA-DPB1 and HLA-DPR1 gene polymorphisms and the interactions between them.
      METHODS: DNA-based typing of HLA-DPB1 and HLA-DRB1 loci at the allele level was
      performed on 65 CBD, 44 beryllium sensitised (BeS) but without CBD and 288 non
      affected, beryllium exposed controls. RESULTS: The DPbetaE69 residue regardless
      of zygosity, but particularly if present on non-*0201 alleles, was of primary
      importance for the development of CBD and BeS, while other negatively charged
      residues DPbetaDE55, 56 and DPbetaDE84, 85 incrementally increased, although not
      independently, the risk. The DPbetaE69 positive alleles with charge -7 or -9 were
      associated with both CBD and BeS. The polymorphic residues DPbetaE69, DPbetaDE55,
      56 and DPbetaDE84, 85 were responsible for the -9 charge and the first two
      residues for the -7 charge. CONCLUSIONS: In the absence of DPbetaE69, DRbetaE71
      is a risk factor for CBD and BeS. DPbetaE69 and DRbetaE71 are adjacent to other
      amino acids that are also negatively charged, suggesting that the positively
      charged Be2+ modifies the local environment of the epitopes in a way that
      promotes interactions between peptides and T cells and results in CBD. Finally,
      the protective effect of the DPB1*0201 positive haplotype may involve particular
      polymorphisms outside of the DPB1 gene.

PMID- 21186202
TI  - Does prenatal cadmium exposure affect fetal and child growth?
AB  - OBJECTIVES: Cadmium is known to be a significant health hazard, but most
      information comes from studies of adults. The effects of exposure to cadmium
      during fetal life on early growth and development remain uncertain. In this study
      we investigated the placental transport of cadmium and the effects of prenatal
      cadmium exposure on fetal and child growth in Taiwan. METHODS: The data in this
      study were from a birth cohort study in Taiwan which started in 2004. Pregnant
      women were recruited from four hospitals and interviewed after delivery to
      collect information on themselves and their infants. Children were followed up to
      obtain information on growth up to 3years of age. Whole blood cadmium
      concentrations in maternal and cord blood samples were measured and the
      relationship with birth size and growth assessed using linear regression and
      mixed models. RESULTS: 321 maternal blood samples and 402 cord blood samples were
      eligible for analysis. Among 289 pairs with maternal and cord blood suitable for
      measurement, the median cadmium concentration in cord blood (0.31MUg/l) was less
      than that in maternal blood (1.05MUg/l), with low correlation between the two
      (r=0.04). An increase in cord blood cadmium was found to be associated with
      newborn decreased head circumference and to be significantly and consistently
      associated with a decrease in height, weight and head circumference up to 3 years
      of age. CONCLUSIONS: Placental transport of cadmium is limited. However, prenatal
      cadmium exposure may have a detrimental effect on head circumference at birth and
      child growth in the first 3years of life.

PMID- 21186203
TI  - Results of surgical management of symptomatic shoulders with partial thickness
      tears of the rotator cuff.
AB  - INTRODUCTION: The optimal management of partial thickness tears of the rotator
      cuff (PTRCT) is still controversial. SOURCE OF DATA: A literature search, on
      PubMed, Cochrane and Google Scholar databases, identified 273 relevant abstracts
      of articles published in peer-reviewed journals. Twenty-three clinical studies
      reporting the outcomes of surgically treated patients affected by PTRCTs were
      selected. AREAS OF AGREEMENT: The different repair approaches results in variable
      functional outcomes. The Coleman Methodology Score (CMS) used to asses the
      quality of the studies showed great heterogeneity in study design, the sample,
      pre- and post-operative diagnostic assessments and the score used to evaluate
      outcomes. The mean CMS value was 67.95 (ranging from 30 to 82). AREAS OF
      CONTROVERSY: The heterogeneity of the treatment options and of the outcome
      assessment methods makes it difficult to compare the results of the different
      studies. GROWING POINTS: There is a need to use standardized pre- and post
      operative assessment methods and functional outcome scores. To improve the
      diagnosis and to choose the best treatment, it may be useful to measure the
      thickness of the rotator cuff to ascertain whether the size correlates with
      outcome. CONCLUSION: There is a lack of scientifically based guidelines, probably
      a result of the relatively low levels of evidence of the studies. There is a need
      for adequately powered randomized clinical trials, using standard diagnostic
      assessment, common and validated scoring system comparing reported outcomes and
      duration of follow-up greater than 2 years.

PMID- 21186204
TI  - Thyroid function in pregnancy.
AB  - Advances in understanding the physiology of thyroid function in normal pregnancy
      have highlighted the importance of the consequences of abnormal function on
      obstetric outcome and foetal well-being. Pubmed search was done using the terms
      thyroid and pregnancy. Areas of agreement are the following: gestational
      normative reference ranges for thyroid function tests are required for proper
      interpretation of any abnormalities. Measurement of thyroid-stimulating
      antibodies and antithyroid peroxidase antibodies is useful for diagnosis of
      thyroid disease in pregnancy. Treatment of Graves' hyperthyroidism should be done
      with propylthiouracil for first trimester only, then carbimazole or methimazole.
      Patients on levothyroxine require an increase in dosage during gestation. Areas
      of controversy are the following: total thyroxine (TT4) versus Free T4 (FT4)
      assays in pregnancy. Screening for thyroid function in early gestation: should it
      be routinely performed on everyone? What tests are appropriate? Growing points
      are the following: physiology of thyroxine delivery to the foetus. Establishment
      of gestational thyroid hormone reference ranges. Evaluation of strategies to
      screen thyroid function in early pregnancy. Areas timely for developing research
      are the following: placental thyroid hormone physiology, thyroid hormone therapy
      and screening thyroid function.

PMID- 21186205
TI  - Claims on health care: a decision-making framework for equity, with application
      to treatment for HIV/AIDS in South Africa.
AB  - Trying to determine how best to allocate resources in health care is especially
      difficult when resources are severely constrained, as is the case in all
      developing countries. This is particularly true in South Africa currently where
      the HIV epidemic adds significantly to a health service already overstretched by
      the demands made upon it. This paper proposes a framework for determining how
      best to allocate scarce health care resources in such circumstances. This is
      based on communitarian claims. The basis of possible claims considered include:
      the need for health care, specified both as illness and capacity to benefit;
      whether or not claimants have personal responsibility in the conditions that have
      generated their health care need; relative deprivation or disadvantage; and the
      impact of services on the health of society and on the social fabric. Ways of
      determining these different claims in practice and the weights to be attached to
      them are also discussed. The implications for the treatment of HIV/AIDS in South
      Africa are spelt out.

PMID- 21186206
TI  - Post mortem scientific sampling and the search for causes of death in intensive
      care: what information should be given and what consent should be obtained?
AB  - PURPOSE: The search for cause of death is important to improve knowledge and
      provide answers for the relatives of the deceased. Medical autopsy following
      unexplained death in hospital is one way to identify cause of death but is
      difficult to carry out routinely. Post mortem sampling (PMS) of tissues via thin
      biopsy needle or 'mini incisions' in the skin may be a useful alternative. A
      study was undertaken to assess how this approach is perceived by intensive care
      doctors and also to evaluate how this practice is considered in ethical terms in
      France. METHODS: A study of PMS practices immediately after death in 10 intensive
      care departments was performed. The medical director of each centre was
      interviewed by telephone and asked to describe practices in their unit and to
      outline the questions raised by this practice. RESULTS: PMS is routinely
      performed in 70% of the units which responded, without systematically obtaining
      formal consent and without precise rules for communicating results. Approaches to
      PMS differed between centres, but all physicians felt that PMS is useful for the
      scientific information it gives and also for the information it provides for
      relatives. All physicians regret the lack of standards to structure PMS
      practices. CONCLUSION: Information from post mortem examinations is important for
      society to inform about causes of death, for doctors to improve practices and for
      decision-makers responsible for organising care. Debate persists regarding the
      balance between individual rights and community interests. It is suggested that
      an approach for identifying cause of death could easily be integrated into the
      relationship between carers and relatives, provided full transparency is
      maintained.

PMID- 21186208
TI  - Retractions in the scientific literature: is the incidence of research fraud
      increasing?
AB  - BACKGROUND: Scientific papers are retracted for many reasons including fraud
      (data fabrication or falsification) or error (plagiarism, scientific mistake,
      ethical problems). Growing attention to fraud in the lay press suggests that the
      incidence of fraud is increasing. METHODS: The reasons for retracting 742 English
      language research papers retracted from the PubMed database between 2000 and 2010
      were evaluated. Reasons for retraction were initially dichotomised as fraud or
      error and then analysed to determine specific reasons for retraction. RESULTS:
      Error was more common than fraud (73.5% of papers were retracted for error (or an
      undisclosed reason) vs 26.6% retracted for fraud). Eight reasons for retraction
      were identified; the most common reason was scientific mistake in 234 papers
      (31.5%), but 134 papers (18.1%) were retracted for ambiguous reasons. Fabrication
      (including data plagiarism) was more common than text plagiarism. Total papers
      retracted per year have increased sharply over the decade (r=0.96; p<0.001), as
      have retractions specifically for fraud (r=0.89; p<0.001). Journals now reach
      farther back in time to retract, both for fraud (r=0.87; p<0.001) and for
      scientific mistakes (r=0.95; p<0.001). Journals often fail to alert the naive
      reader; 31.8% of retracted papers were not noted as retracted in any way.
      CONCLUSIONS: Levels of misconduct appear to be higher than in the past. This may
      reflect either a real increase in the incidence of fraud or a greater effort on
      the part of journals to police the literature. However, research bias is rarely
      cited as a reason for retraction.

PMID- 21186209
TI  - Use of energy deposition spectrometer Liulin for individual monitoring of
      aircrew.
AB  - Silicon energy deposition spectrometer Liulin was primarily developed for cosmic
      radiation monitoring onboard spacecrafts. Nowadays, Liulin type detectors are
      also used to characterise radiation field on board aircraft, at alpine
      observatories and behind the shielding of heavy ion accelerators. In this work,
      experiments and calibrations performed in these radiation fields are presented
      and the method developed for calculation of ambient dose equivalent H*(10) on
      board aircraft is described. Since 2001, a simple method employing the energy
      deposition spectra had been used to determine H*(10) on board aircraft but, in
      2004, it became clear that the resulting values were strongly biased at locations
      close to Earth's equator. An improved method for the determination of H*(10) on
      board aircraft using the Liulin detector was developed. It took into account the
      composition of the radiation field via the ratio of absorbed doses D(low) and
      D(neut) reflecting the contributions from low-LET particles and neutrons,
      respectively. It resulted in much better agreement with the EPCARD computer code
      for all aircraft locations; relative differences were within 11 % for low-LET and
      20 % for neutron components of H*(10).

PMID- 21186207
TI  - The challenge of defining standards of prevention in HIV prevention trials.
AB  - As new HIV prevention tools are developed, researchers face a number of ethical
      and logistic questions about how and when to include novel HIV prevention
      strategies and tools in the standard prevention package of ongoing and future HIV
      prevention trials. Current Joint United Nations Programme on HIV/AIDS
      (UNAIDS)/World Health Organization (WHO) guidance recommends that participants in
      prevention trials receive 'access to all state of the art HIV risk reduction
      methods', and that decisions about adding new tools to the prevention package be
      made in consultation with 'all relevant stakeholders'. The guidance, however,
      leaves open questions of both process and implementation. In March 2009, the
      Global Campaign for Microbicides, UNAIDS and the Centers for Disease Control and
      Prevention convened a consultation to develop practical answers to these
      questions. Fifty-nine diverse participants, including researchers, ethicists,
      advocates and policymakers, worked to develop consensus criteria on when to
      include new HIV prevention tools in future trials. Participants developed a set
      of questions to guide decision-making, including: whether the method has been
      recommended by international bodies or adopted at a national level; the size of
      the effect and weight of the evidence; relevance to the trial population; whether
      the tool has been approved or introduced in the trial country; whether adding the
      tool might lead to trial futility; outstanding safety issues and status of the
      trial. Further work is needed to develop, implement and evaluate approaches to
      facilitate meaningful stakeholder participation in this deliberative process.

PMID- 21186210
TI  - Design of a multi-element TEPC for neutron monitoring.
AB  - Tissue-equivalent proportional counters (TEPCs) have long been considered
      suitable candidate instruments for more accurate neutron monitors in nuclear
      power plants. It has also been recognised that the production of truly light
      weight devices based on TEPCs requires further effort directed towards increasing
      their sensitivity and decreasing their physical size. This paper deals with the
      construction of a multi-element TEPC (METEPC) designed to have the sensitivity of
      a 12.7-cm (5-in.) diameter spherical TEPC, but with approximately one-tenth of
      its physical size. Construction of the METEPC is achieved by machining 61
      elongated cylindrical cavities in a single block of A150 TE plastic. Comparative
      measurements carried out in neutron fields with mean energies ranging from 34 to
      354 keV demonstrate that the METEPC constructed does match the sensitivity of a 5
      in. spherical TEPC and that microdosimetric lineal energy spectra measured with
      both detectors have the same features and show the same changes with neutron
      radiation quality.

PMID- 21186211
TI  - Delayed effects of chronic low-dose high linear energy transfer (LET) radiation
      on mice in vivo.
AB  - In the present work, the delayed effects of chronic high linear energy transfer
      (LET) radiation in polychromatic erythrocytes (PCEs) of mice bone marrow were
      investigated in vivo. Irradiation of the two-month-old SHK white mongrel random
      bred male mice was performed in the radiation field behind the concrete shield of
      the accelerator of 70 GeV protons to accumulate doses of 0.005-0.16 Gy. The
      dependence of the biological response on dose, adaptive response (AR) and genomic
      instability (GI) in F(1) and F(2) generations from males irradiated with doses of
      0.005 and 0.16 Gy and from males exposed to combined action of immunomodulator
      bendazol hydrochloride (BH) and of 0.16 Gy irradiation, were examined using the
      micronucleus formation test. The data demonstrated that irradiation of mice with
      these doses lead to an increase in the level of cytogenetic damage and induces no
      AR. With analysis of the bone marrow radiosensitivity to 1.5 Gy of X rays and the
      capacity to AR it was found that the chronic high-LET irradiation of parents
      induced the GI at least two generations. The combined exposure to BH and the dose
      of 0.16 Gy induces no AR in F(0) generation but induces AR in F(1) and F(2)
      offspring.

PMID- 21186212
TI  - Physical models implemented in the GEANT4-DNA extension of the GEANT-4 toolkit
      for calculating initial radiation damage at the molecular level.
AB  - The ROSIRIS project aims to study the radiobiology of integrated systems for
      medical treatment optimisation using ionising radiations and evaluate the
      associated risk. In the framework of this project, one research focus is the
      interpretation of the initial radio-induced damage in DNA created by ionising
      radiation (and detected by gamma-H2AX foci analysis) from the track structure of
      the incident particles. In order to calculate the track structure of ionising
      particles at a nanometric level, the Geant4 Monte Carlo toolkit was used. Geant4
      (Object Oriented Programming Architecture in C++) offers a common platform,
      available free to all users and relatively easy to use. Nevertheless, the current
      low-energy threshold for electromagnetic processes in GEANT4 is set to 1 keV (250
      eV using the Livermore processes), which is an unsuitable value for nanometric
      applications. To lower this energy threshold, the necessary interaction processes
      and models were identified, and the corresponding available cross sections
      collected from the literature. They are mostly based on the plane-wave Born
      approximation (first Born approximation, or FBA) for inelastic interactions and
      on semi-empirical models for energies where the FBA fails (at low energies). In
      this paper, the extensions that have been introduced into the 9.3 release of the
      Geant4 toolkit are described, the so-called Geant4-DNA extension, including a set
      of processes and models adapted in this study and permitting the simulation of
      electron (8 eV-1 MeV), proton (100 eV-100 MeV) and alpha particle (1 keV-10 MeV)
      interactions in liquid water.

PMID- 21186213
TI  - Cellular burdens and biological effects on tissue level caused by inhaled radon
      progenies.
AB  - In the case of radon exposure, the spatial distribution of deposited radioactive
      particles is highly inhomogeneous in the central airways. The object of this
      research is to investigate the consequences of this heterogeneity regarding
      cellular burdens in the bronchial epithelium and to study the possible biological
      effects at tissue level. Applying computational fluid and particle dynamics
      techniques, the deposition distribution of inhaled radon daughters has been
      determined in a bronchial airway model for 23 min of work in the New Mexico
      uranium mine corresponding to 0.0129 WLM exposure. A numerical epithelium model
      based on experimental data has been utilised in order to quantify cellular hits
      and doses. Finally, a carcinogenesis model considering cell death-induced cell
      cycle shortening has been applied to assess the biological responses. Present
      computations reveal that cellular dose may reach 1.5 Gy, which is several orders
      of magnitude higher than tissue dose. The results are in agreement with the
      histological finding that the uneven deposition distribution of radon progenies
      may lead to inhomogeneous spatial distribution of tumours in the bronchial
      airways. In addition, at the macroscopic level, the relationship between cancer
      risk and radiation burden seems to be non-linear.

PMID- 21186214
TI  - Construction issues surrounding a portable four-band neutron detection system.
AB  - Solid state-based surface barrier detectors (SBDs) have been employed in neutron
      radiation dosimetry for over half a century, each combination of detector
      featuring positives and pitfalls. Here the implications of constructing a
      portable neutron spectrometer device, based upon moderating high-density
      polyethylene substrates and utilising different types of large-area solid state
      SBDs, are discussed.

PMID- 21186215
TI  - Active personal dosemeters in interventional radiology: tests in laboratory
      conditions and in hospitals.
AB  - The work package 3 of the ORAMED project, Collaborative Project (2008-11)
      supported by the European Commission within its seventh Framework Programme, is
      focused on the optimisation of the use of active personal dosemeters (APDs) in
      interventional radiology and cardiology (IR/IC). Indeed, a lack of appropriate
      APD devices is identified for these specific fields. Few devices can detect low
      energy X rays (20-100 keV), and none of them are specifically designed for
      working in pulsed radiation fields. The work presented in this paper consists in
      studying the behaviour of some selected APDs deemed suitable for application in
      IR/IC. For this purpose, measurements under laboratory conditions, both with
      continuous and pulsed X-ray beams, and tests in real conditions on site in
      different European hospitals were performed. This study highlights the
      limitations of APDs for this application and the need of improving the APD
      technology so as to fulfil all needs in the IR/IC field.

PMID- 21186216
TI  - A Monte Carlo simulation of monoenergetic neutrons traversing rectangular and
      spherical polyethylene moderators.
AB  - A Monte Carlo-based simulation of the transport of a series of monoenergetic
      neutron sources through first a rectangular block of 0.93 g cm(-3) density
      polyethylene and secondly through a sphere made of the same substance is
      presented here. In both instances, the neutron fields are monitored at closely
      spread intervals through the moderator mass, producing a lot of data in the
      process. To reduce the amount of data presented, a figure of merit is created by
      estimating the cross section for each discrete neutron energy and by applying
      this to the number of neutrons present of each energy giving an arbitrary
      response figure. This work was undertaken in order to aid the design and
      development of a novel neutron spectrometer.

PMID- 21186217
TI  - Brazilian gamma-neutron dosemeter: response to 241AmBe and 252Cf neutron sources.
AB  - With the aim of improving the monitoring of workers potentially exposed to
      neutron radiation in Brazil, the IPEN/CNEN-SP in association with PRO-RAD
      designed and developed a passive individual gamma-neutron mixed-field dosemeter
      calibrated to be used to (241)AmBe sources. To verify the dosimetry system
      response to different neutron spectra, prototypes were irradiated with a (252)Cf
      source and evaluated using the dose-calculation algorithm developed for (241)AmBe
      sources.

PMID- 21186218
TI  - A novel technique using DNA denaturation to detect multiply induced single-strand
      breaks in a hydrated plasmid DNA molecule by X-ray and 4He2+ ion irradiation.
AB  - To detect multiple single-strand breaks (SSBs) produced in plasmid DNA molecules
      by direct energy deposition from radiation tracks, we have developed a novel
      technique using DNA denaturation by which irradiated DNA is analysed as single
      strand DNA (SS-DNA). The multiple SSBs that arise in both strands of DNA, but do
      not induce a double-strand break, are quantified as loss of SS-DNA using agarose
      gel electrophoresis. We have applied this method to X-ray and (4)He(2+) ion
      irradiated samples of fully hydrated pUC18 plasmid DNA. The fractions of both SS
      DNA and closed circular DNA (CC-DNA) exponentially decrease with the increasing
      dose of X rays and (4)He(2+) ions. The efficiency of the loss of SS-DNA was half
      that of CC-DNA for both types of irradiation, indicating that one of two strands
      in DNA is not broken when one SSB is produced in CC-DNA by irradiation. Contrary
      to our initial expectation, these results indicate that SSBs are not multiply
      induced even by high linear energy transfer radiation distributed in both
      strands.

PMID- 21186219
TI  - Radiation dose to members of public residing around uranium mining complex,
      Jaduguda, Jharkhand, India.
AB  - Uranium mining activities in the Jaduguda region of Jharkhand state, India have
      been carried out for the last five decades. Radioactive releases from mines, ore
      processing facility and tailings pond may increase the natural radiation dose to
      members of the public residing around the complex. It is, therefore, imperative
      to investigate the radiological condition around the uranium mining complex and
      assess the dose received by them. In the present study, it was estimated that the
      average radiation dose from all exposure pathways to the public living in
      villages around the mining complex is 2.5 mSv y(-1) and around 50 % contributed
      due to inhalation of radon and its progeny. The external radiation dose due to
      terrestrial and cosmic activity is estimated to be 1.1 mSv y(-1), which is 40 %
      of the total dose and ingestion dose contributes only 3% to the total dose.

PMID- 21186220
TI  - High survival of frozen cells irradiated with gamma radiation.
AB  - Cell storage in liquid nitrogen (LN) offers the most secure method of cell
      preservation even if cryopreserved cells are exposed to natural background of
      ionising radiation (IR). A lot of experiments have demonstrated that IR can
      induce damages in living cells, but only a little information regarding the
      response of cryopreserved cells is available. To investigate the effect of IR on
      frozen and unfrozen cells, peripheral blood mononuclear cells were directly
      irradiated at room temperature, then immediately frozen, or frozen and then
      irradiated in LN with different doses of gamma rays. After thawing, cells were
      incubated and death fraction was evaluated at different time points.
      Interestingly, the percentages of dead cells induced by IR gradually increased
      with both dose radiation and incubation time and were significantly lower for
      cells irradiated at -196 degrees C than those irradiated at room temperature.

PMID- 21186221
TI  - Design concept for a novel SQUID-based microdosemeter.
AB  - The interest in proton and ion-beam therapy has increased substantially in recent
      years, leading the Bureau International des Poids et Mesures to recommend that a
      new quantity be defined to account for the biological effect of treatment
      modalities used in the radiotherapy. In response, we have begun work on the
      design of a new microbolometer based on the inductive superconducting transition
      edge detector (ISTED) designed at the National Physical Laboratory. Our work aims
      to expand the use of the ISTED from its current use as an infra-red detector to
      the measurement of energy deposition of photons, hadrons and ions by
      incorporating a tissue-equivalent absorber. We present here the work carried out
      till date, including the detection of single visible photons, with an energy
      resolution of 0.2 eV and a time response of a few microseconds, using a 15-um
      Superconducting QUantum Interference Device operating at 9 K. We also describe
      thermal computational modelling carried out for a simple ISTED absorber. Finally,
      we discuss the work currently in progress and that to be carried out before the
      detector is realised.

PMID- 21186222
TI  - A method of identification of abnormal glow curves in individual monitoring using
      CaSO4:Dy teflon TLD and hot gas reader.
AB  - In the present study, a method of identifying abnormal glow curves to
      electronically screen the glow curves of TL readout is presented. The method is
      based on the fact that the shape of an abnormal glow curve differs from the shape
      of a normal one. A few criteria for defining the normal shape of glow curves are
      arrived at by analysing the glow curves of dosemeters exposed to various doses in
      laboratory conditions and read at different elapsed time post irradiation. About
      300 glow curves of dosemeters used for monthly monitoring were analysed as per
      these criteria and the effectiveness of the method is observed for total counts
      as low as 150 uSv equivalent.

PMID- 21186223
TI  - Wavelet-SVM classification and automatic recognition of unstained viable cells in
      phase-contrast microscopy.
AB  - Irradiation of individual cultured mammalian cells with a pre-selected number of
      ions down to one ion per single cell is a useful experimental approach to
      investigating the low-dose ionising radiation exposure effects and thus
      contributing to a more realistic human cancer risk assessment. One of the crucial
      tasks of all the microbeam apparatuses is the visualisation, recognition and
      positioning of every individual cell of the cell culture to be irradiated. Before
      irradiations, mammalian cells (specifically, Chinese hamster V79 cells) are
      seeded and grown as a monolayer on a mylar surface used as the bottom of a
      specially designed holder. Manual recognition of unstained cells in a bright
      field microscope is a time-consuming procedure; therefore, a parallel algorithm
      has been conceived and developed in order to speed up this irradiation protocol
      step. Many technical problems have been faced to overcome the complexity of the
      images to be analysed: cell discrimination in an inhomogeneous background, among
      many disturbing bodies mainly due to the mylar surface roughness and culture
      medium bodies; cell shapes, depending on how they attach to the surface, which
      phase of the cell cycle they are in and on cell density. Preliminary results of
      the recognition and classification based on a method of wavelet kernels for the
      support vector machine classifier will be presented.

PMID- 21186224
TI  - A protocol for evidence-based targeting and evaluation of statewide strategies
      for preventing falls among community-dwelling older people in Victoria,
      Australia.
AB  - BACKGROUND: Falls are a significant threat to the safety, health and independence
      of older citizens. Despite the now substantial evidence about effective falls
      prevention interventions, translation into falls reductions has not yet been
      fully realised. While the hip fracture rate is decreasing, the number and rate of
      fall-related hospital admissions among older people is increasing. The challenge
      now is to deliver the most effective interventions efficiently at a population
      level, and for these interventions to be taken up by older people. OBJECTIVE: To
      support the development, and evaluation of, effective falls prevention policy and
      practice in the state of Victoria, Australia. METHODS: The RE-AIM model (Reach,
      Efficacy, Adoption, Implementation, Maintenance) was used to identify strategies
      for an effective programme. Research objectives were developed to support the
      strategies. These include: (1) identification of subgroups of older people most
      frequently admitted to hospital for falls; (2) examining the acceptability of
      established falls interventions; (3) identification of factors that encourage and
      support relevant lifestyle changes; (4) identifying opportunities to incorporate
      confirmed interventions in existing programmes and services; (5) developing
      guidelines for sustainability. The research results will subsequently guide
      strategy details for the falls prevention plan. RE-AIM will provide the framework
      for the evaluation structure. OUTCOME MEASURES MEASURES: to monitor the
      implementation of the selected interventions will be determined for each
      intervention, based on the five key factors of the RE-AIM model. The overall
      effect of the falls prevention plan will be monitored by time series analysis of
      fall-related hospital admission rates for community-dwelling older people.

PMID- 21186225
TI  - QRS-T morphology measured from exercise electrocardiogram as a predictor of
      cardiac mortality.
AB  - AIMS: Total cosine R-to-T (TCRT) measured from the standard 12-lead
      electrocardiogram (ECG) reflects the spatial relationship between depolarization
      and repolarization wavefronts and a low TCRT value is a marker of poor prognosis.
      We tested the hypothesis that measurement of TCRT or QRS/T angle from exercise
      ECG would provide even more powerful prognostic information. METHODS AND RESULTS:
      The prognostic significances of TCRT and QRS/T angle were assessed from exercise
      ECG recordings in 1297 patients [age 56 +/- 13 years (mean +/- SD), 67% males]
      undergoing a clinically indicated bicycle stress-test and the subsequent follow
      up. During an average follow-up of 45 +/- 12 months, 74 patients died (5.7%); 34
      (2.6%) were cardiac deaths, and 24 (1.9%) were sudden cardiac deaths. Total
      cosine R-to-T and QRS/T angle exhibited a correlation with the RR intervals in
      the total cohort, but the individual responses were variable, e.g. median
      correlation of TCRT-RR was 0.89 with an inter-quartile range from 0.55 to 0.98. A
      reduced correlation of TCRT-RR during the recovery phase of exercise ECG
      predicted cardiac death [adjusted heart rate (HR) 3.5, 95% confidence interval
      (CI): 1.8-6.8, P= 0.001] similarly as the baseline TCRT measured from ECG at rest
      (adjusted HR 3.4, 95% CI: 1.4-8.1, P= 0.01). The poor correlation between the
      TCRT-RR both during the exercise and recovery was specifically related to a risk
      of sudden cardiac death (adjusted HR 6.2, 95% CI: 2.1-17.8, P< 0.001).
      CONCLUSIONS: Loss of rate-adaptation of the spatial relationship between
      depolarization and repolarization wavefronts is a strong predictor of cardiac
      death, especially of sudden cardiac death.

PMID- 21186226
TI  - Electrophysiology of anterograde right-atrial and left-atrial inputs to the
      atrioventricular node in patients with atrioventricular nodal re-entrant
      tachycardia.
AB  - AIMS: To study anterograde atrioventricular (A-V) nodal electrophysiological
      properties through the right-atrial (Ri) and left-atrial inputs (Li) under the
      pharmacological autonomic blockade (AUB) in patients with slow-fast A-V nodal re
      entrant tachycardia (AVNRT) and in controls. METHODS AND RESULTS: Twenty-nine
      patients with slow-fast AVNRT and 15 control subjects were included. Programmed
      stimulation with single extrastimulus was performed from the right atrial
      appendage to test the Ri, and from the posterolateral coronary sinus to test the
      Li. The AUB was induced with intravenous atropine (0.04 mg/kg) and metoprolol
      (0.15 mg/kg). The A-V nodal conduction times, refractoriness, discontinuous
      conduction (>= 40 ms atrial-His interval 'jump'), and inducibility of AVNRT or
      reciprocating beats were compared. The A-V nodal conduction times were longer:
      (i) through the Ri than Li, (ii) in patients than controls, and (iii) in baseline
      than after AUB--at slow rates in both groups and at fast rates in patients
      through the right input only (P < 0.05-0.001). A significantly longer slow
      pathway effective refractory period was demonstrated through the Li than the Ri
      in patients in baseline (P < 0.05). The discontinuous conduction was demonstrated
      94 times in 25 of 29 (83%) patients and 15 times in 6 of 15 (40%) controls (P <
      0.01), and was most frequently encountered with the Ri testing. Likewise,
      inducibility was manifested most frequently with the Ri testing (P = 0.08), and
      decreased after AUB during this testing only (P = 0.05). CONCLUSION: The inherent
      magnitude of discordance of A-V nodal conduction velocity, refractoriness, and
      parasympathetic modulation between the Ri and Li to the A-V node may play a role
      in the aetiology of AVNRT.

PMID- 21186227
TI  - A shock in time saves ablation?

PMID- 21186228
TI  - Heart rates in cardiac resynchronization: the art of optimal device programming.

PMID- 21186229
TI  - Effects of physical exercise on cardiac dyssynchrony in patients with impaired
      left ventricular function.
AB  - AIMS: The purpose of this study was to determine the effect of exercise on
      dyssynchrony in patients with left ventricular dysfunction. METHODS AND RESULTS:
      Sixty patients with a left ventricular ejection fraction (LVEF) <= 35% were
      studied. Interventricular mechanical delay (IVMD), intraventricular mechanical
      delay [Ts-(lateral-septal)], and left ventricular filling ratio were measured at
      rest and during exercise. Significant IVMD was defined as a difference between
      aortic and pulmonary pre-ejection times of >40 ms. Intraventricular dyssynchrony
      was defined as a Ts-(lateral-septal) >65 ms. Forty-five patients with no
      dyssynchrony at rest were analysed (age 62 +/- 14; LVEF 28 +/- 6%) and compared
      with a control group of 15 patients with known dyssynchrony at rest. None of the
      45 patients without dyssynchrony at rest developed dyssynchrony during exercise
      based on IVMD and Ts-(lateral-septal). In the control group, IVMD decreased from
      65 +/- 19 to 33 +/- 11 ms (P< 0.001) during exercise, whereas Ts-(lateral-septal)
      did not change. Persistence of dyssynchrony during exercise (decrease of IVMD
      <60%) was significantly associated with response to cardiac resynchronization
      therapy (CRT). Whereas all 10 responders had persistent dyssynchrony during
      exercise, 4 of the 5 non-responders (80%) had an exercise-induced decrease of
      IVMD >60% (P< 0.004). CONCLUSION: Exercise does not elicit mechanical
      dyssynchrony in patients without dyssynchrony at rest. In patients with
      significant dyssynchrony at rest, exercise-induced decrease of IVMD is common.
      Persistence of dyssynchrony during exercise might be a novel predictor of
      response to CRT.

PMID- 21186230
TI  - Usefulness of transoesophageal echocardiography before circumferential pulmonary
      vein ablation in patients with atrial fibrillation: is it really mandatory?
AB  - AIMS: Transoesophageal echocardiography (TEE) is recommended prior to
      circumferential pulmonary vein ablation (CPVA) in patients with atrial
      fibrillation (AF) to identify left atrial (LA) or left atrial appendage (LAA)
      wall thrombi. It is not clear whether all patients undergoing CPVA should receive
      pre-procedural TEE. We wanted to assess the incidence of LA thrombus in these
      patients and to identify factors associated with its presence. METHODS AND
      RESULTS: Consecutive patients referred for CPVA from 2004 to 2009 underwent TEE
      within 48 h prior to the procedure. Of 408 patients included in the study, 6
      patients (1.47%) had LA thrombi, persistent AF, and LA dilation. Compared with
      patients without thrombus, these six patients had larger LA diameter (P = 0.0001)
      and more frequently were women (P = 0.002), had persistent AF (P = 0.04), and had
      underlying structural cardiac disease (P = 0.014). The likelihood of presenting
      LA thrombus increased with the number of these four risk factors present (P <
      0.001). None of the patients with paroxysmal AF and without LA dilation had LA
      thrombus. A cut-off value of 48.5 mm LA diameter yielded 83% sensitivity, 92%
      specificity, and a 10.1 likelihood ratio to predict LA thrombus appearance.
      CONCLUSION: The incidence of LA thrombus prior to CPVA is low. Persistent AF,
      female sex, structural cardiopathy, and LA dilation were associated with the
      presence of LA thrombus. Our data suggest that the use of TEE prior to CPVA to
      detect LA thrombi might not be needed in patients with paroxysmal AF and no LA
      dilation or structural cardiopathy.

PMID- 21186231
TI  - Pulmonary vein antrum isolation leads to a significant decrease of left atrial
      size.
AB  - AIMS: Pulmonary vein antrum isolation (PVAI) is an effective treatment for atrial
      fibrillation (AF); however, its impact on left atrial (LA) size is unknown. This
      study evaluates the impact of PVAI on LA size, and whether LA size differs
      between patients with a successful outcome and patients with AF recurrences.
      METHODS AND RESULTS: Seventy-nine patients (76% male, mean age 56 +/- 8 years)
      with symptomatic, drug refractory AF (70% paroxysmal, 30% persistent/permanent)
      underwent radiofrequency PVAI. Ablation lesions were created encircling right and
      left pulmonary venous ostia in pairs. The endpoint was complete isolation of all
      pulmonary veins. Magnetic resonance imaging was performed before and 4 months
      after PVAI and LA volume was measured by manually tracing the LA area. Clinical
      follow-up was at 1, 3, 6, 12, and 24 months. Rhythm status was determined by
      history, electrocardiogram, and 48 h Holter monitoring. After a mean follow-up of
      12 +/- 5 months, 62 patients (78%) were free of AF (72% without antiarrhythmic
      drugs). In the total group, LA volume decreased from 104 +/- 27 mL to 91 +/- 25
      mL, P < 0.001. Patients with a successful outcome showed a decrease in LA volume
      of 103 +/- 27 mL to 89 +/- 24 mL, P < 0.001. Among patients with AF recurrences,
      LA volume decreased from 105 +/- 29 mL to 95 +/- 27 mL, P = 0.012. No significant
      difference was seen between the change in LA volume in both subgroups, P = 0.27.
      CONCLUSION: Pulmonary vein antrum isolation in patients with AF resulted in a
      significant decrease of LA size. There was no relation between the decrease in LA
      size and the recurrence of AF after PVAI.

PMID- 21186232
TI  - Timing of defibrillator implant after acute myocardial infarction: what's new?

PMID- 21186233
TI  - Catastrophic consequence of a pacing lead in the wrong chamber.

PMID- 21186234
TI  - Comparing the importance of different aspects of quality of life to older adults
      across diverse cultures.
AB  - BACKGROUND: there is limited research examining the relative importance of
      aspects of quality of life (QOL) to older adults across cultures. OBJECTIVE: to
      examine the relative importance of 31 internationally agreed areas of QOL to
      older adults in 22 countries in relation to health status, age and level of
      economic development. DESIGN: a survey quota sampling design was used to collect
      cross-cultural data. This study reports a secondary analysis of WHOQOL-OLD pilot
      study, which was collected simultaneously in 22 centres. SETTINGS: a variety of
      community, primary, secondary and tertiary health care settings located in
      Australia, France, Switzerland, England, Scotland, USA, Israel, Spain, Japan,
      China (mainland and Hong Kong), Turkey, Lithuania, Czech Republic, Hungary,
      Canada, Norway, Sweden, Denmark, Germany, Brazil and Uruguay. PARTICIPANTS: the
      total sample contained 7,401 people over 60 years with a mean age of 73.1 years;
      57.8% were women and 70.1% considered themselves 'healthy'. RESULTS: there were
      significant differences in the importance given to various aspects of QOL for
      people living in medium and high-development countries. Culture explained 15.9%
      of the variance in the importance ratings of QOL. However, the interaction showed
      that cultural differences were reduced once health status, gender and age were
      taken into account. The importance of QOL to age bands in different cultures was
      not significantly affected by whether or not participants perceived themselves to
      be healthy. CONCLUSION: understanding the self-reported importance of diverse
      aspects of QOL for different cultures and for healthy and less healthy people may
      assist national and international policy makers to decide on priorities for the
      development of programmes for the ageing population.

PMID- 21186235
TI  - Re: "A pooled analysis of extremely low-frequency magnetic fields and childhood
      brain tumors".

PMID- 21186236
TI  - Survival in cancer patients with previous hospitalization for sarcoidosis: a
      Swedish population-based cohort study during 1964-2006.
AB  - BACKGROUND: Sarcoidosis has been reported to be associated with an increased risk
      of cancer; however, little information is available about the prognosis for
      sarcoidosis patients diagnosed with cancer. PATIENTS AND METHODS: A population
      based cohort of sarcoidosis patients was identified from Swedish registers. Cause
      specific and overall hazard ratios (HRs) were estimated by using Cox regression
      model to show the probability of death in the study group compared with the
      control population. RESULTS: A total of 1167 sarcoidosis patients were identified
      with subsequent cancer compared with 1,023,725 cancer patients without
      sarcoidosis from 1964 to 2006, showing a significant survival disparity [overall
      HR 1.21, 95% confidence interval (CI) 1.13-1.30 and cause-specific HR 1.16, 95%
      CI 1.08-1.27]. Site-specific analyses revealed that an overall mortality excess
      in sarcoidosis patients was observed for six cancers in comparison with a cancer
      specific mortality excess for four cancers. Notably, stratified analyses showed
      that the prognosis was worse for cancer patients diagnosed below age 65 years.
      Cancer sites with significant mortality excess after sarcoidosis were mutually
      exclusive for men and women. CONCLUSIONS: A previously diagnosed sarcoidosis
      worsens the prognosis of cancer, preferentially for those diagnosed at a
      relatively younger age. The underlying mechanisms and more prognostic factors
      warrant further investigation.

PMID- 21186237
TI  - Hysterectomy and risk of cardiovascular disease: a population-based cohort study.
AB  - AIMS: Hysterectomy for benign indications is one of the commonest surgical
      procedures in women, but the association between the procedure and cardiovascular
      disease (CVD) is not fully understood. In this population-based cohort study, we
      studied the effects of hysterectomy, with or without oopherectomy, on the risk of
      later life CVD. METHODS AND RESULTS: Using nationwide healthcare registers, we
      identified all Swedish women having a hysterectomy on benign indications between
      1973 and 2003 (n = 184,441), and non-hysterectomized controls (n = 640,043). Main
      outcome measure was the first hospitalization or death of incident CVD (coronary
      heart disease, stroke, or heart failure). Occurrence of CVD was determined by
      individual linkage to the Inpatient Register. In women below age 50 at study
      entry, hysterectomy was associated with a significantly increased risk of CVD
      during follow-up [hazard ratio (HR), 1.18, 95% confidence interval (CI), 1.13
      1.23; HR, 2.22, 95% CI, 1.01-4.83; and HR, 1.25, 95% CI, 1.06-1.48; in women
      without oopherectomy, with oopherectomy before or at study entry, respectively,
      using women without hysterectomy or oopherectomy as reference]. In women aged 50
      or above at study entry, there were no significant associations between
      hysterectomy and incident CVD. CONCLUSIONS: Hysterectomy in women aged 50 years
      or younger substantially increases the risk for CVD later in life and
      oopherectomy further adds to the risk of both coronary heart disease and stroke.

PMID- 21186238
TI  - Circulating CD31+/Annexin V+ microparticles correlate with cardiovascular
      outcomes.
AB  - AIMS: CD31+/Annexin V+ microparticles (MPs) are increased in patients with
      cardiovascular risk factors and impaired coronary endothelial function. We
      evaluated whether MPs are an independent marker for cardiovascular events in
      patients with stable coronary artery disease (CAD). METHODS AND RESULTS: The
      number of CD31+/Annexin V+ MP was determined by flow cytometry in 200 patients
      (age 66.1+/-10.4 years) and correlated with cardiovascular outcomes. The median
      follow-up time for major adverse cardiovascular and cerebral event (MACCE)-free
      survival was 6.1 (6.0/6.4) years. Four patients were lost to follow-up. A first
      MACCE occurred in 72 patients (37%). Microparticle levels were significantly
      higher in patients with MACCE compared with patients without event (P=0.004). The
      prevalence of diabetes (P=0.02) and male gender (P=0.05) was significantly
      related to the MP level. In multivariate analysis (cardiovascular risk factors,
      number of diseased vessels, use of angiotensin-converting enzyme-inhibitors and
      statins), high MP levels were associated with a higher risk for cardiovascular
      death [Hazard ratio (HR) 4.0, 95% confidence interval (CI) 1.1-14.6; P=0.04], the
      need for revascularization (HR 2.4, 95% CI 1.3-4.4; P=0.005), and the occurrence
      of a first MACCE (HR 2.3, 95% CI 1.4-3.8; P=0.001). Inclusion of the MP level
      into a classical risk factor model substantially increased c-statistics from
      0.637 (95% CI: 0.557-0.717) to 0.702 (95% CI: 0.625-0.780) (P=0.03). CONCLUSION:
      The level of circulating CD31+/Annexin V+ MPs is an independent predictor of
      cardiovascular events in stable CAD patients and may be useful for risk
      stratification.

PMID- 21186239
TI  - Mycorrhizal associations and reproductive isolation in three closely related
      Orchis species.
AB  - BACKGROUND AND AIMS: The maintenance of species boundaries in sympatric
      populations of closely related species requires some kind of reproductive
      isolation that limits gene flow among species and/or prevents the production of
      viable progeny. Because in orchids mycorrhizal fungi are needed for seed
      germination and subsequent seedling establishment, orchid-mycorrhizal
      associations may be involved in acting as a post-mating barrier. METHODS: We
      investigated the strength of post-mating barriers up to the seed germination
      stage acting between three closely related Orchis species (Orchis anthropophora,
      O. militaris and O. purpurea) and studied the role of mycorrhizal fungi in
      hybridization by burying seed packets of pure and hybrid seeds. After retrieval
      and assessment of seed germination, the fungi associating with protocorms
      originating from hybrid and pure seeds were determined and compared with those
      associating with adult individuals using DNA array technology. RESULTS: Whereas
      pre-zygotic post-mating barriers were rather weak in most crosses, post-zygotic
      post-mating barriers were stronger, particularly when O. purpurea was crossed
      with O. anthropophora. Germination trials in the field showed that seed
      germination percentages of hybrid seeds were in most cases lower than those
      originating from pure crosses. In all species pair combinations, total post
      mating reproductive isolation was asymmetric. Protocorms associated with a
      smaller range of fungal symbionts than adult plants, but there was considerable
      overlap in mycorrhizal associations between protocorms and their respective
      parents. CONCLUSIONS: Our results suggest that mycorrhizal associations
      contribute little to reproductive isolation. Pre-mating barriers are probably the
      main factors determining hybridization rates between the investigated species.

PMID- 21186240
TI  - Linking carbon supply to root cell-wall chemistry and mechanics at high altitudes
      in Abies georgei.
AB  - BACKGROUND AND AIMS: The mobile carbon supply to different compartments of a tree
      is affected by climate, but its impact on cell-wall chemistry and mechanics
      remains unknown. To understand better the variability in root growth and
      biomechanics in mountain forests subjected to substrate mass movement, we
      investigated root chemical and mechanical properties of mature Abies georgei var.
      smithii (Smith fir) growing at different elevations on the Tibet-Qinghai Plateau.
      METHODS: Thin and fine roots (0.1-4.0 mm in diameter) were sampled at three
      different elevations (3480, 3900 and 4330 m, the last corresponding to the
      treeline). Tensile resistance of roots of different diameter classes was measured
      along with holocellulose and non-structural carbon (NSC) content. KEY RESULTS:
      The mean force necessary to break roots in tension decreased significantly with
      increasing altitude and was attributed to a decrease in holocellulose content.
      Holocellulose was significantly lower in roots at the treeline (29.5 +/- 1.3 %)
      compared with those at 3480 m (39.1 +/- 1.0 %). Roots also differed significantly
      in NSC, with 35.6 +/- 4.1 mg g(-1) dry mass of mean total soluble sugars in roots
      at 3480 m and 18.8 +/- 2.1 mg g(-1) dry mass in roots at the treeline.
      CONCLUSIONS: Root mechanical resistance, holocellulose and NSC content all
      decreased with increasing altitude. Holocellulose is made up principally of
      cellulose, the biosynthesis of which depends largely on NSC supply. Plants
      synthesize cellulose when conditions are optimal and NSC is not limiting. Thus,
      cellulose synthesis in the thin and fine roots measured in our study is probably
      not a priority in mature trees growing at very high altitudes, where climatic
      factors will be limiting for growth. Root NSC stocks at the treeline may be
      depleted through over-demand for carbon supply due to increased fine root
      production or winter root growth.

PMID- 21186241
TI  - An in vitro investigation of peak insertion torque values of six commercially
      available mini-implants.
AB  - This study compared peak insertion torque values of six commercially available
      self-drilling mini-implants [Mini Spider(r) screw (1.5 * 8 mm), Infinitas(r) (1.5
      * 9 mm), Vector TAS(r) (1.4 * 8 mm), Dual Top(r) (1.6 * 8 mm), Tomas Pin(r) (1.6
      * 8 mm), and Ortho-Easy(r) (1.7 * 6, 8, and 10 mm)]. Twenty implants each were
      drilled into acrylic rods at a speed of 8 rpm using a motorized torque
      measurement stand, and the values were recorded in Newton centimetres (Ncm). A
      further 20 Ortho-Easy(r) implants with a length of 6 and 10 mm were tested at 8
      rpm; 20 implants of 6 mm length were also tested at 4 rpm. Kaplan-Meier estimates
      of the peak torque values were compared using the log-rank test with multiple
      comparisons evaluated by Sidak's test. There were significant differences in the
      maximum torque values for different mini-implants with the same length. The Mini
      Spider(r) screw and Infinitas(r) showed the lowest average torque values (6.5 and
      12.4 Ncm) compared with Vector TAS(r), Dual ToP(r), Tomas Pin(r), and Ortho
      Easy(r) (30.9, 29.4, 25.4, and 24.8 Ncm, respectively). There was no correlation
      between the diameter of the implants and torque values. The Tomas Pin(r) showed
      the largest standard deviation (7.7 Ncm) and the Dual Top(r) implant the smallest
      (0.6 Ncm). Different insertion speeds did not result in significant differences
      in peak torque values but the 6 mm mini-implants showed significantly higher
      torque values than the 8 and 10 mm implants. Using a 'torque limiting'
      screwdriver or pre-drilling cortical bone to reduce insertion, torque appears
      justified for some of the tested implants.

PMID- 21186242
TI  - Pseudo-response regulator (PRR) homologues of the moss Physcomitrella patens:
      insights into the evolution of the PRR family in land plants.
AB  - The pseudo-response regulators (PRRs) are the circadian clock component proteins
      in the model dicot Arabidopsis thaliana. They contain a receiver-like domain
      (RLD) similar to the receiver domains of the RRs in the His-Asp phosphorelay
      system, but the RLDs lack the phosphoacceptor aspartic acid residue invariably
      conserved in the receiver domains. To study the evolution of PRR genes in plants,
      here we characterize their homologue genes, PpPRR1, PpPRR2, PpPRR3 and PpPRR4,
      from the moss Physcomitrella patens. In the phylogenetic analysis, PpPRRs cluster
      together, sister to an angiosperm PRR gene subfamily, illustrating their close
      relationships with the angiosperm PRRs. However, distinct from the angiosperm
      sequences, the RLDs of PpPRR2/3/4 exhibit a potential phosphoacceptor aspartic
      acid-aspartic acid-lysine (DDK) motif. Consistently, the PpPRR2 RLD had
      phosphotransfer ability in vitro, suggesting that PpPRR2 functions as an RR. The
      PpPRR1 RLD, on the other hand, shows a partially diverged DDK motif, and it did
      not show phosphotransfer ability. All PpPRRs were expressed in a circadian and
      light-dependent manner, with differential regulation between PpPRR2/4 and
      PpPRR1/3. Altogether, our results illustrate that PRRs originated from an RR(s)
      and that there are intraspecific divergences among PpPRRs. Finally, we offer
      scenarios for the evolution of the PRR family in land plants.

PMID- 21186243
TI  - Nitric oxide: a key factor behind the dysfunctionality of endothelial progenitor
      cells in diabetes mellitus type-2.
AB  - Diabetes mellitus type-2 (DM-2) contributes to atherogenesis by inducing
      endothelial cell injury and dysfunction. Endothelial progenitor cells (EPCs) are
      essential to blood vessel formation, can differentiate into mature endothelial
      cells, and promote the repair of damaged endothelium. In DM-2, the circulating
      EPC count is low and their functionality is impaired. The mechanisms that
      underlie this reduced count and impaired functionality are poorly understood.
      Nitric oxide (NO) is a short-lived signalling molecule that is produced by
      vascular endothelial cells and participates in the maintenance of vascular tone.
      NO is also known to participate in other physiological processes, such as cell
      survival, proliferation, and migration. The bioavailability of NO is reduced in
      EPCs from DM-2 patients. Interestingly, an inverse relationship exists between
      the reduction in NO bioavailability in EPCs and the patient's plasma glucose and
      glycated haemoglobin levels. In addition, NO bioavailability in EPCs correlates
      with plasma oxidized low-density lipoprotein levels in DM-2. Although this
      reduction in NO bioavailability could be attributed to oxidative stress in DM-2
      patients, it also may be due to impairment of one or more members of the protein
      signalling cascades that are responsible for NO production. The stimulation of NO
      production or its signalling cascades in EPCs may increase their numbers and
      improve their function, thus attenuating endothelium damage, independent of the
      vasodilatory effects of NO. This review summarizes the metabolic alterations that
      underlie the molecular mechanisms that may be responsible for EPC decrease and
      dysfunction in DM-2 with emphasis on the involvement of the NO system.

PMID- 21186244
TI  - Ct3d: tracking microglia motility in 3D using a novel cosegmentation approach.
AB  - MOTIVATION: Cell tracking is an important method to quantitatively analyze time
      lapse microscopy data. While numerous methods and tools exist for tracking cells
      in 2D time-lapse images, only few and very application-specific tracking tools
      are available for 3D time-lapse images, which is of high relevance in
      immunoimaging, in particular for studying the motility of microglia in vivo.
      RESULTS: We introduce a novel algorithm for tracking cells in 3D time-lapse
      microscopy data, based on computing cosegmentations between component trees
      representing individual time frames using the so-called tree-assignments. For the
      first time, our method allows to track microglia in three dimensional confocal
      time-lapse microscopy images. We also evaluate our method on synthetically
      generated data, demonstrating that our algorithm is robust even in the presence
      of different types of inhomogeneous background noise. AVAILABILITY: Our algorithm
      is implemented in the ct3d package, which is available under
      http://www.picb.ac.cn/patterns/Software/ct3d; supplementary videos are available
      from http://www.picb.ac.cn/patterns/Supplements/ct3d.

PMID- 21186245
TI  - PUGSVM: a caBIGTM analytical tool for multiclass gene selection and predictive
      classification.
AB  - Phenotypic Up-regulated Gene Support Vector Machine (PUGSVM) is a cancer
      Biomedical Informatics Grid (caBIGTM) analytical tool for multiclass gene
      selection and classification. PUGSVM addresses the problem of imbalanced class
      separability, small sample size and high gene space dimensionality, where
      multiclass gene markers are defined by the union of one-versus-everyone
      phenotypic upregulated genes, and used by a well-matched one-versus-rest support
      vector machine. PUGSVM provides a simple yet more accurate strategy to identify
      statistically reproducible mechanistic marker genes for characterization of
      heterogeneous diseases. AVAILABILITY: http://www.cbil.ece.vt.edu/caBIG
      PUGSVM.htm.

PMID- 21186246
TI  - A sub-pathway-based approach for identifying drug response principal network.
AB  - MOTIVATION: The high redundancy of and high degree of cross-talk between
      biological pathways hint that a sub-pathway may respond more effectively or
      sensitively than the whole pathway. However, few current pathway enrichment
      analysis methods account for the sub-pathways or structures of the tested
      pathways. We present a sub-pathway-based enrichment approach for identifying a
      drug response principal network, which takes into consideration the quantitative
      structures of the pathways. RESULT: We validated this new approach on a
      microarray experiment that captures the transcriptional profile of dexamethasone
      (DEX)-treated human prostate cancer PC3 cells. Compared with GeneTrail and DAVID,
      our approach is more sensitive to the DEX response pathways. Specifically, not
      only pathways but also the principal components of sub-pathways and networks
      related to prostate cancer and DEX response could be identified and verified by
      literature retrieval.

PMID- 21186247
TI  - A computationally efficient modular optimal discovery procedure.
AB  - MOTIVATION: It is well known that patterns of differential gene expression across
      biological conditions are often shared by many genes, particularly those within
      functional groups. Taking advantage of these patterns can lead to increased
      statistical power and biological clarity when testing for differential expression
      in a microarray experiment. The optimal discovery procedure (ODP), which
      maximizes the expected number of true positives for each fixed number of expected
      false positives, is a framework aimed at this goal. Storey et al. introduced an
      estimator of the ODP for identifying differentially expressed genes. However,
      their ODP estimator grows quadratically in computational time with respect to the
      number of genes. Reducing this computational burden is a key step in making the
      ODP practical for usage in a variety of high-throughput problems. RESULTS: Here,
      we propose a new estimate of the ODP called the modular ODP (mODP). The existing
      'full ODP' requires that the likelihood function for each gene be evaluated
      according to the parameter estimates for all genes. The mODP assigns genes to
      modules according to a Kullback-Leibler distance, and then evaluates the
      statistic only at the module-averaged parameter estimates. We show that the mODP
      is relatively insensitive to the choice of the number of modules, but
      dramatically reduces the computational complexity from quadratic to linear in the
      number of genes. We compare the full ODP algorithm and mODP on simulated data and
      gene expression data from a recent study of Morrocan Amazighs. The mODP and full
      ODP algorithm perform very similarly across a range of comparisons. AVAILABILITY:
      The mODP methodology has been implemented into EDGE, a comprehensive gene
      expression analysis software package in R, available at
      http://genomine.org/edge/.

PMID- 21186248
TI  - Voroprot: an interactive tool for the analysis and visualization of complex
      geometric features of protein structure.
AB  - We present Voroprot, an interactive cross-platform software tool that provides a
      unique set of capabilities for exploring geometric features of protein structure.
      Voroprot allows the construction and visualization of the Apollonius diagram
      (also known as the additively weighted Voronoi diagram), the Apollonius graph,
      protein alpha shapes, interatomic contact surfaces, solvent accessible surfaces,
      pockets and cavities inside protein structure. AVAILABILITY: Voroprot is
      available for Windows, Linux and Mac OS X operating systems and can be downloaded
      from http://www.ibt.lt/bioinformatics/voroprot/.

PMID- 21186249
TI  - Genome-scale phylogenetics: inferring the plant tree of life from 18,896 gene
      trees.
AB  - Phylogenetic analyses using genome-scale data sets must confront incongruence
      among gene trees, which in plants is exacerbated by frequent gene duplications
      and losses. Gene tree parsimony (GTP) is a phylogenetic optimization criterion in
      which a species tree that minimizes the number of gene duplications induced among
      a set of gene trees is selected. The run time performance of previous
      implementations has limited its use on large-scale data sets. We used new
      software that incorporates recent algorithmic advances to examine the performance
      of GTP on a plant data set consisting of 18,896 gene trees containing 510,922
      protein sequences from 136 plant taxa (giving a combined alignment length of >2.9
      million characters). The relationships inferred from the GTP analysis were
      largely consistent with previous large-scale studies of backbone plant phylogeny
      and resolved some controversial nodes. The placement of taxa that were present in
      few gene trees generally varied the most among GTP bootstrap replicates.
      Excluding these taxa either before or after the GTP analysis revealed high levels
      of phylogenetic support across plants. The analyses supported magnoliids sister
      to a eudicot + monocot clade and did not support the eurosid I and II clades.
      This study presents a nuclear genomic perspective on the broad-scale phylogenic
      relationships among plants, and it demonstrates that nuclear genes with a history
      of duplication and loss can be phylogenetically informative for resolving the
      plant tree of life.

PMID- 21186250
TI  - A single amino acid mutation at position 170 of human parainfluenza virus type 1
      fusion glycoprotein induces obvious syncytium formation and caspase-3-dependent
      cell death.
AB  - An escape mutant of human parainfluenza virus type 1 (hPIV1), which was selected
      by serial passage in the presence of a sialidase inhibitor, 4-O
      thiocarbamoylmethyl-2-deoxy-2,3-didehydro-N-acetylneur-aminic acid (TCM
      Neu5Ac2en), exhibited remarkable syncytium formation and virus-induced cell death
      in LLC-MK2 cells but no difference in susceptibility for the sialidase inhibitor
      TCM-Neu5Ac2en from that of wild-type hPIV1 strain C35 (WT). The mutant virus also
      had higher replication and plaque formation abilities. The mutant virus acquired
      two amino acid mutations, Glu to Gly at position 170 and Ala to Glu 442 in fusion
      (F) glycoprotein, but no mutations in haemaggulutinin-neuraminidase (HN)
      glycoprotein. Using cells co-expressing F and HN genes with site-specific
      mutagenesis, we demonstrated that a point mutation of Glu to Gly at position 170,
      which was estimated to be located in hPIV1 F glycoprotein heptad repeat 1, was
      required for obvious syncytium formation and caspase-3-dependent cell death. In
      contrast, wild-type F glycoprotein induced no synctium formation or cell death.
      The findings suggest that a single amino acid mutation of hPIV1 F glycoprotein
      promotes syncytium formation that is followed by caspase-3-dependent cell death.

PMID- 21186251
TI  - Barbituric acid derivative BAS 02104951 inhibits PKCepsilon, PKCeta,
      PKCepsilon/RACK2 interaction, Elk-1 phosphorylation in HeLa and PKCepsilon and
      eta translocation in PC3 cells following TPA-induction.
AB  - Protein kinase C (PKC) is a family of at least 10 isozymes involved in the
      activation of different signal transduction pathways. The exact function of these
      isozymes is not known at present. Isozyme-selective inhibitors would be important
      to explain the function of the different PKCs and are anticipated to have
      pharmaceutical potential. Here we report that the small organic molecule BAS
      02104951 [5-(1,3-benzodioxol-5-ylmethylene)-1-(phenylmethyl)-2,4,6(1H,3H,5H)
      pyrimidinetrion], a barbituric acid derivative, inhibited PKCeta and PKCepsilon
      in vitro (IC(50) 18 and 36 uM, respectively). BAS 02104951 also inhibited the
      interaction of PKCepsilon with its adaptor protein receptor for activated C
      kinase 2 (RACK2) (IC(50) 28.5 uM). BAS 02104951 also inhibited 12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced Elk-1 phosphorylation in HeLa
      cells, translocation of PKCepsilon and PKCeta to the membrane following treatment
      of PC3 cells with TPA. The compound did not inhibit the proliferation of PC3 and
      HeLa cells. BAS 02104951 can be used as selective inhibitor of PKCepsilon in
      cells not expressing PKCeta and may serve as a basis for the rational development
      of a selective inhibitor of PKCepsilon or PKCeta, or for an inhibitor of the
      PKCepsilon/RACK2 interaction.

PMID- 21186252
TI  - Developing a smoking cessation program for Turkish-speaking migrants in
      Switzerland: novel findings and promising effects.
AB  - INTRODUCTION: Recent studies show that smoking prevalence in the Turkish-speaking
      migrant population in Switzerland is substantially higher than in the general
      population. A specific group treatment for Turkish-speaking migrants was
      developed and tested in order to provide the migrant population with equal access
      to smoking cessation programs and to improve the migration-sensitive quality of
      such programs by sociocultural targeting. METHODS: The evaluation of the program
      included quantitative (questionnaires t1 and t2 and follow-up by telephone) and
      qualitative methods (participant observation and semi-structured interviews).
      RESULTS: The results showed that 37.7% of the 61 participants were smoke free at
      the 12-month follow-up. The factors of being in a partnership and using nicotine
      replacement products during the program were positively associated with
      successful cessation. We also demonstrated the importance of "strong ties"
      (strong relationships between participants) and the sensitivity of the program to
      sociocultural (e.g., social aspects of smoking in Turkish culture, which were
      addressed in relapse prevention), socioeconomic (e.g., low financial resources,
      which were addressed by providing the course for free), and migration-specific
      (e.g., underdeveloped access to smoking cessation programs, which was addressed
      using outreach strategy for recruiting) issues. CONCLUSIONS: Overall, the smoking
      cessation program was successfully tested and is now becoming implemented as a
      regular service of the Swiss Public Health Program for Tobacco Prevention (by the
      Swiss Association for Smoking Prevention).

PMID- 21186253
TI  - Predictors of 3-month abstinence in smokers attending stop-smoking clinics in
      Malaysia.
AB  - INTRODUCTION: Much is known about the predictors of success in quitting smoking.
      In particular, nicotine dependence, but not strength of motivation to stop,
      appears to predict abstinence. However, to date, studies have come almost
      exclusively from Western countries. More data are needed on the cross-cultural
      generalizability of these findings. METHODS: One hundred and ninety-eight smokers
      attending 5 stop-smoking clinics in Malaysia completed a questionnaire prior to
      their target quit date and were followed up 3 months after this date. Predictors
      included sociodemographic variables, smoking patterns, past history of quitting,
      characteristics of current quit attempt, and smoking motives as well as nicotine
      dependence (Fagerstrom Test for Nicotine Dependence [FTND]) and self-rated
      strength of motivation of stop. RESULTS: At 3-month follow-up, 35.4% (95% CI:
      28.7-42.0) of participants reported being abstinent. A backward elimination
      multiple logistic regression identified a number of significant predictors of
      success, including strength of motivation to stop (adjusted odds ratio [OR]:
      3.05, 95% CI: 1.28-7.25). FTND did not predict success. CONCLUSIONS: Motivation
      and nicotine dependence may play different roles in explaining variation in
      ability to stop smoking in different cultures.

PMID- 21186254
TI  - Invasion in multi-type populations: the role of phenotypic robustness and
      fluctuations.
AB  - We study the invasion dynamics of a mutant population characterized by an
      increased phenotypic variability with respect to the incumbent population, with
      an emphasis on the effects of increased phenotypic robustness and fluctuations
      induced by small system size. This model is based on recent experimental and
      theoretical results which hint at the possibility that inactivation of certain
      genes, either by the effect of mutations or by pharmacological intervention,
      leads to the liberation of cryptic genetic variation which, in turn, produces a
      host of new phenotypic variants. We present a theoretical framework based on the
      so-called evolutionary formalism where the population dynamics can be analysed in
      terms of a suitably defined entropy function. This analytical framework allows us
      to ascertain the effect that increased phenotypic robustness of the new
      phenotypes has on the invasion probability and show that increased phenotypic
      robustness improves the fixation probability of the mutant population. The
      stochastic effects due to small population size are evaluated by means of
      numerical simulations. Our results are discussed in the light of recent results
      concerning the effect of diversity on the progression from a premalignant
      condition, such as the Barret's esophagus, to a fully developed tumour.

PMID- 21186255
TI  - Dynamics of population communities with prey migrations and Allee effects: a
      bifurcation approach.
AB  - The population dynamics of predator-prey systems in the presence of patch
      specific predators are explored in a setting where the prey population has access
      to both habitats. The emphasis is in situations where patch-prey abundance drives
      prey dispersal between patches, with the fragile prey populations, i.e.
      populations subject to the Allee effect. The resulting 3D and 4D non-linear
      systems depending on some parameters, which reflect 'measures' of factors under
      consideration, support rich dynamics and in particular a diverse number of
      predator-prey life history outcomes. The model's mathematical analysis is carried
      out via submodels that focus in lower-dimensional settings. The outcomes depend
      on and, in fact, are quite sensitive to the structure of the system, the range of
      parameter values and initial conditions. We show that the system can support
      multistability and a diverse set of predator-prey life-history dynamics that
      include rather complex dynamical system outcomes. It is argued that, in general,
      evolution should favour heterogeneous settings including Allee effects, prey
      refuges and patch-specific predators.

PMID- 21186257
TI  - The role of reinfection and partner notification in the efficacy of Chlamydia
      screening programs.
AB  - Repeated Chlamydia trachomatis infections after treatment are common. One reason
      is reinfection from untreated partners in ongoing sexual partnerships.
      Mathematical models that are used to predict the impact of screening on reducing
      chlamydia prevalence often do not incorporate reinfection and might overestimate
      the expected impact. We describe a pair compartmental model that explicitly
      incorporates sexual partnership duration and reinfection. The pair model predicts
      a weaker impact of screening when compared directly with a model that does not
      accommodate partnerships. Effective management of sex partners to prevent
      reinfection might need to be strengthened in chlamydia control programs.

PMID- 21186256
TI  - Bacterial pore-forming cytolysins induce neuronal damage in a rat model of
      neonatal meningitis.
AB  - BACKGROUND: Group B Streptococcus (GBS) and Streptococcus pneumoniae (SP) are
      leading causes of bacterial meningitis in neonates and children. Each pathogen
      produces a pore-forming cytolytic toxin, beta-hemolysin/cytolysin (beta-h/c) by
      GBS and pneumolysin by SP. The aim of this study was to understand the role of
      these pore-forming cytotoxins, in particular of the GBS beta-h/c, as potential
      neurotoxins in experimental neonatal meningitis. METHODS: Meningitis was induced
      in 7- and 11-day-old rats by intracisternal injection of wild type (WT) GBS or SP
      and compared with isogenic beta-h/c- or pneumolysin-deficient mutants, or a
      double mutant of SP deficient in pneumolysin and hydrogen peroxide production.
      RESULTS: GBS beta-h/c and SP pneumolysin contributed to neuronal damage, worsened
      clinical outcome and weight loss, but had no influence on the early kinetics of
      leukocyte influx and bacterial growth in the cerebrospinal fluid. In vitro, beta
      h/c-induced neuronal apoptosis occurred independently of caspase-activation and
      was not preventable by the broad spectrum caspase-inhibitor z-VAD-fmk.
      CONCLUSIONS: These data suggest that both cytolytic toxins, the GBS beta-h/c and
      SP pneumolysin, contribute to neuronal damage in meningitis and extend the
      concept of a key role for bacterial pore-forming cytolysins in the pathogenesis
      and sequelae of neonatal meningitis.

PMID- 21186258
TI  - Penetration and activation of brain endothelium by Salmonella enterica serovar
      Typhimurium.
AB  - Salmonella meningitis is a serious disease of the central nervous system, common
      particularly in Africa. Here, we show that Salmonella enterica serovar
      Typhimurium is able to adhere, invade, and penetrate human brain microvascular
      endothelial cells (hBMECs), the single-cell layer constituting the blood-brain
      barrier (BBB). Cellular invasion was dependent on host actin cytoskeleton
      rearrangements, while expression of a functional type III secretion system was
      not essential. In addition, Salmonella infection activated a proinflammatory
      immune response targeting neutrophil signaling and recruitment. Salmonella
      invasion and immune activation may represent a crucial step in the penetration of
      the BBB and development of Salmonella meningitis.

PMID- 21186259
TI  - Calculation of the anterograde velocity of varicella-zoster virions in a human
      sciatic nerve during shingles.
AB  - Zoster of the sciatic nerve, the longest nerve in the human body, is an uncommon
      event. We cared for a child with sciatic nerve zoster who had severe pain over
      the lower back 6 days before appearance of vesicular rash on the foot in the L4
      dermatome. On the basis of the clinical data, we calculated an anterograde
      velocity for the varicella zoster virion of 5.55 mm/h or .0015 mm/s. Because
      there is no good animal model of varicella zoster virus reactivation from
      latency, this experiment of nature fills a notable gap in our knowledge about
      varicella zoster virus neuronal transportation.

PMID- 21186260
TI  - Tuberculin-specific T cells are reduced in active pulmonary tuberculosis compared
      to LTBI or status post BCG vaccination.
AB  - Functional characteristics of tuberculosis (TB)-specific CD4 T cells were studied
      in clinically active pulmonary TB (n = 21) and high TB exposure including LTBI (n
      = 17). Following tuberculin stimulation, activated CD4 T cells were identified by
      flow-cytometry (CD154 up-regulation, degranulation, interferon gamma [IFN-gamma],
      tumor necrosis factor alpha [TNF-alpha], and interleukin 2 [IL-2? production).
      Interestingly, CD154 up-regulation accounted for ~80% of activated CD4 T cells in
      the active TB group but just 40% in the controls, whereas IFN-gamma accounted for
      only ~50% of activated cells in each group. The frequencies of CD4 T cells
      displaying at least 1 activation marker discriminated better between the groups
      than those displaying degranulation or IFN-gamma production alone.

PMID- 21186261
TI  - Brain. Editorial.

PMID- 21186262
TI  - The human pre-Botzinger complex identified.

PMID- 21186263
TI  - Post-acute delivery of erythropoietin induces stroke recovery by promoting
      perilesional tissue remodelling and contralesional pyramidal tract plasticity.
AB  - The promotion of post-ischaemic motor recovery remains a major challenge in
      clinical neurology. Recently, plasticity-promoting effects have been described
      for the growth factor erythropoietin in animal models of neurodegenerative
      diseases. To elucidate erythropoietin's effects in the post-acute ischaemic
      brain, we examined how this growth factor influences functional neurological
      recovery, perilesional tissue remodelling and axonal sprouting of the
      corticorubral and corticobulbar tracts, when administered intra
      cerebroventricularly starting 3 days after 30 min of middle cerebral artery
      occlusion. Erythropoietin administered at 10 IU/day (but not at 1 IU/day),
      increased grip strength of the contralesional paretic forelimb and improved motor
      coordination without influencing spontaneous locomotor activity and exploration
      behaviour. Neurological recovery by erythropoietin was associated with structural
      remodelling of ischaemic brain tissue, reflected by enhanced neuronal survival,
      increased angiogenesis and decreased reactive astrogliosis that resulted in
      reduced scar formation. Enhanced axonal sprouting from the ipsilesional pyramidal
      tract into the brainstem was observed in vehicle-treated ischaemic compared with
      non-ischaemic animals, as shown by injection of dextran amines into both motor
      cortices. Despite successful remodelling of the perilesional tissue,
      erythropoietin enhanced axonal sprouting of the contralesional, but not
      ipsilesional pyramidal tract at the level of the red and facial nuclei. Moreover,
      molecular biological and histochemical studies revealed broad anti-inflammatory
      effects of erythropoietin in both hemispheres together with expression changes of
      plasticity-related molecules that facilitated contralesional axonal growth. Our
      study establishes a plasticity-promoting effect of erythropoietin after stroke,
      indicating that erythropoietin acts via recruitment of contralesional rather than
      of ipsilesional pyramidal tract projections.

PMID- 21186264
TI  - A founder mutation in Anoctamin 5 is a major cause of limb-girdle muscular
      dystrophy.
AB  - The limb-girdle muscular dystrophies are a group of disorders with wide genetic
      and clinical heterogeneity. Recently, mutations in the ANO5 gene, which encodes a
      putative calcium-activated chloride channel belonging to the Anoctamin family of
      proteins, were identified in five families with one of two previously identified
      disorders, limb-girdle muscular dystrophy 2L and non-dysferlin Miyoshi muscular
      dystrophy. We screened a candidate group of 64 patients from 59 British and
      German kindreds and found the truncating mutation, c.191dupA in exon 5 of ANO5 in
      20 patients, homozygously in 15 and in compound heterozygosity with other ANO5
      variants in the rest. An intragenic single nucleotide polymorphism and an
      extragenic microsatellite marker are in linkage disequilibrium with the mutation,
      suggesting a founder effect in the Northern European population. We have further
      defined the clinical phenotype of ANO5-associated muscular dystrophy. Patients
      show adult onset proximal lower limb weakness with highly raised serum creatine
      kinase values (average 4500 IU/l) and frequent muscle atrophy and asymmetry of
      muscle involvement. Onset varies from the early 20 s to 50 s and the weakness is
      generally slowly progressive, with most patients remaining ambulant for several
      decades. Distal presentation is much less common but a milder degree of distal
      lower limb weakness is often observed. Upper limb strength is only mildly
      affected and cardiac and respiratory function is normal. Females appear less
      frequently affected. In the North of England population we have identified eight
      patients with ANO5 mutations, suggesting a minimum prevalence of 0.27/100,000,
      twice as common as dysferlinopathy. We suggest that mutations in ANO5 represent a
      relatively common cause of adult onset muscular dystrophy with high serum
      creatine kinase and that mutation screening, particularly of the common mutation
      c.191dupA, should be an early step in the diagnostic algorithm of adult limb
      girdle muscular dystrophy patients.

PMID- 21186265
TI  - Reversal of autophagy dysfunction in the TgCRND8 mouse model of Alzheimer's
      disease ameliorates amyloid pathologies and memory deficits.
AB  - Autophagy, a major degradative pathway for proteins and organelles, is essential
      for survival of mature neurons. Extensive autophagic-lysosomal pathology in
      Alzheimer's disease brain contributes to Alzheimer's disease pathogenesis,
      although the underlying mechanisms are not well understood. Here, we identified
      and characterized marked intraneuronal amyloid-beta peptide/amyloid and lysosomal
      system pathology in the Alzheimer's disease mouse model TgCRND8 similar to that
      previously described in Alzheimer's disease brains. We further establish that the
      basis for these pathologies involves defective proteolytic clearance of neuronal
      autophagic substrates including amyloid-beta peptide. To establish the pathogenic
      significance of these abnormalities, we enhanced lysosomal cathepsin activities
      and rates of autophagic protein turnover in TgCRND8 mice by genetically deleting
      cystatin B, an endogenous inhibitor of lysosomal cysteine proteases. Cystatin B
      deletion rescued autophagic-lysosomal pathology, reduced abnormal accumulations
      of amyloid-beta peptide, ubiquitinated proteins and other autophagic substrates
      within autolysosomes/lysosomes and reduced intraneuronal amyloid-beta peptide.
      The amelioration of lysosomal function in TgCRND8 markedly decreased
      extracellular amyloid deposition and total brain amyloid-beta peptide 40 and 42
      levels, and prevented the development of deficits of learning and memory in fear
      conditioning and olfactory habituation tests. Our findings support the pathogenic
      significance of autophagic-lysosomal dysfunction in Alzheimer's disease and
      indicate the potential value of restoring normal autophagy as an innovative
      therapeutic strategy for Alzheimer's disease.

PMID- 21186266
TI  - Serotonin transporter interacts with the PDGFbeta receptor in PDGF-BB-induced
      signaling and mitogenesis in pulmonary artery smooth muscle cells.
AB  - The serotonin transporter (SERT) and the platelet-derived growth factor receptor
      (PDGFR) have been implicated in both clinical and experimental pulmonary
      hypertension (PH) and the facilitation of pulmonary artery smooth muscle cell
      (PASMC) growth. To gain a better understanding of the possible relationship of
      these two cell surface molecules we have explored interactions between SERT and
      PDGFR. We have previously demonstrated that SERT transactivates PDGFRbeta in
      serotonin-stimulated PASMC proliferation. We now provide evidence for a role for
      SERT in PDGF-BB signaling and PASMC proliferation by using pharmacological
      inhibitors, genetic ablation, and construct overexpression of SERT. The results
      show that four tested SERT blockers dose dependently inhibit PDGF-stimulated
      human and bovine PASMC proliferation with comparable efficacy to that of PDGFR
      inhibitors, whereas 5-HT1B or 5-HT2A receptor inhibitors had no effect.
      Combinations of the SERT and PDGFR inhibitors led to synergistic/additive
      inhibition. Similarly, PDGF-induced PASMC proliferation was attenuated by small
      interfering RNA downregulation of SERT. Inhibition of SERT in PASMCs attenuated
      PDGF-induced phosphorylation of PDGFRbeta, Akt, and p38 but not Erk.
      Overexpression of SERT in HEK293 cells led to enhanced Akt phosphorylation by
      PDGF, which was blunted by a SERT PDZ motif mutant, indicating the mechanistic
      need for the PDZ motif of SERT in PDGF signaling. Furthermore,
      coimmunoprecipitation experiments showed that SERT and PDGFRbeta become
      physically associated upon PDGF stimulation. In total, the data show for the
      first time an important interactive relationship between SERT and the PDGFRbeta
      in the production of PASMC proliferation triggered by PDGF that may be important
      in PH.

PMID- 21186267
TI  - PKR-dependent CHOP induction limits hyperoxia-induced lung injury.
AB  - Supplemental O(2) is commonly employed in patients with respiratory failure;
      however, hyperoxia is also a potential contributor to lung injury. In animal
      models, hyperoxia causes oxidative stress in the lungs, resulting in increased
      inflammation, edema, and permeability. We hypothesized that oxidative stress from
      prolonged hyperoxia leads to endoplasmic reticulum (ER) stress, resulting in
      activation of the unfolded protein response (UPR) and induction of CCAAT enhancer
      binding protein homologous protein (CHOP), a transcription factor associated with
      cell death in the setting of persistent ER stress. To test this hypothesis, we
      exposed the mouse lung epithelial cell line MLE-12 to 95% O(2) for 8-24 h and
      evaluated for evidence of UPR induction and CHOP induction. Hyperoxia caused
      increased CHOP expression without other evidence of UPR activation. Because CHOP
      expression is preceded by phosphorylation of the alpha-subunit of the eukaryotic
      initiation factor-2 (eIF2alpha), we evaluated the role of double-stranded RNA
      activated protein kinase (PKR), a non-UPR-associated eIF2alpha kinase. Hyperoxia
      caused PKR phosphorylation, and RNA interference knockdown of PKR attenuated
      hyperoxia-induced CHOP expression. In vivo, hyperoxia induced PKR phosphorylation
      and CHOP expression in the lungs without other biochemical evidence for ER
      stress. Additionally, Ddit3(-/-) (CHOP-null) mice had increased lung edema and
      permeability, indicating a previously unknown protective role for CHOP after
      prolonged hyperoxia. We conclude that hyperoxia increases CHOP expression via an
      ER stress-independent, PKR-dependent pathway and that increased CHOP expression
      protects against hyperoxia-induced lung injury.

PMID- 21186268
TI  - Impact of repeated increases in shear stress via reactive hyperemia and handgrip
      exercise: no evidence of systematic changes in brachial artery FMD.
AB  - Reactive hyperemia (RH) creates an uncontrolled, transient increase in brachial
      artery (BA) shear stress (SS) for flow-mediated dilation (FMD) assessment. In
      contrast, handgrip exercise (HGEX) can create similar, sustained SS increases
      over repeated trials. The purpose of this study was to examine the impact of
      repeated SS elevation via RH or HGEX and the relationship between RH and HGEX
      %FMD. BA diameter and blood velocity were assessed with echo and Doppler
      ultrasound in 20 healthy subjects. Visit A consisted of four 6-min HGEX trials
      (HGEX trials 1-4) at the intensity required to achieve a shear rate (SR = mean
      blood velocity/BA diameter; an estimate of SS) of 65 s(-1). Visit B consisted of
      four RH trials (RH trials 1-4). The RH SR area under the curve (AUC) was higher
      in trial 1 versus trial 3 and trial 4 (P = 0.019 and 0.047). The HGEX mean SR was
      similar across trials (mean SR = 66.1 +/- 5.8 s(-1), P = 0.152). There were no
      differences in %FMD across trials or tests (RH trial 1: 6.9 +/- 3.5%, trial 2:
      6.9 +/- 2.3%, trial 3: 7.1 +/- 3.5%, and trial 4: 7.0 +/- 2.8%; HGEX trial 1: 7.3
      +/- 3.6%, trial 2: 7.0 +/- 3.6%, trial 3: 6.5 +/- 3.5%, and trial 4: 6.8 +/-
      2.9%, P = 0.913). No relationship between subject's RH %FMD and HGEX %FMD was
      detected (r(2) = 0.12, P = 0.137). However, with response normalization, a
      relationship emerged (RH %FMD/SR AUC vs. HGEX %FMD/mean SR, r(2) = 0.44, P =
      0.002). In conclusion, with repeat trials, there were no systematic changes in RH
      or HGEX %FMD. The relationship between normalized RH and HGEX %FMD suggests that
      endothelial responses to different SS profiles provide related information
      regarding endothelial function.

PMID- 21186269
TI  - The hypothalamic arcuate nucleus: a new site of cardiovascular action of
      angiotensin-(1-12) and angiotensin II.
AB  - The hypothalamic arcuate nucleus (ARCN) has been reported to play a significant
      role in cardiovascular regulation. It has been hypothesized that the ARCN may be
      one of the sites of cardiovascular actions of angiotensins (ANGs). Experiments
      were carried out in urethane-anesthetized, artificially ventilated, adult male
      Wistar rats. The ARCN was identified by microinjections of N-methyl-d-aspartic
      acid (NMDA; 10 mM). Microinjections (50 nl) of ANG-(1-12) (1 mM) into the ARCN
      elicited increases in mean arterial pressure (MAP), heart rate (HR), and greater
      splanchnic nerve activity (GSNA). The tachycardic responses to ANG-(1-12) were
      attenuated by bilateral vagotomy. The cardiovascular responses elicited by ANG-(1
      12) were attenuated by microinjections of ANG II type 1 receptor (AT(1)R)
      antagonists but not ANG type 2 receptor (AT(2)R) antagonist. Combined inhibition
      of ANG-converting enzyme (ACE) and chymase in the ARCN abolished ANG-(1-12)
      induced responses. Microinjections of ANG II (1 mM) into the ARCN also increased
      MAP and HR. Inhibition of ARCN by microinjections of muscimol (1 mM) attenuated
      the pressor and tachycardic responses to intravenously administered ANG-(1-12)
      and ANG II (300 pmol/kg each). These results indicated that 1) microinjections of
      ANG-(1-12) into the ARCN elicited increases in MAP, HR, and GSNA; 2) HR responses
      were mediated via both sympathetic and vagus nerves; 3) AT(1)Rs, but not AT(2)Rs,
      in the ARCN mediated ANG-(1-12)-induced responses; 4) both ACE and chymase were
      needed to convert ANG-(1-12) to ANG II in the ARCN; and 5) ARCN plays a role in
      mediating the cardiovascular responses to circulating ANGs.

PMID- 21186271
TI  - Na+ channel distribution and electrophysiological heterogeneities in guinea pig
      ventricular wall.
AB  - We sought to explore the distribution pattern of Na(+) channels across
      ventricular wall, and to determine its functional correlates, in the guinea pig
      heart. Voltage-dependent Na(+) channel (Na(v)) protein expression levels were
      measured in transmural samples of ventricular tissue by Western blotting.
      Isolated, perfused heart preparations were used to record monophasic action
      potentials and volume-conducted ECG, and to measure effective refractory periods
      (ERPs) and pacing thresholds, in order to assess excitability, electrical
      restitution kinetics, and susceptibility to stimulation-evoked tachyarrhythmias
      at epicardial and endocardial stimulation sites. In both ventricular chambers,
      Na(v) protein expression was higher at endocardium than epicardium, with
      midmyocardial layers showing intermediate expression levels. Endocardial
      stimulation sites showed higher excitability, as evidenced by lower pacing
      thresholds during regular stimulation and downward displacement of the strength
      interval curve reconstructed after extrasystolic stimulation compared with
      epicardium. ERP restitution assessed over a wide range of pacing rates showed
      greater maximal slope and faster kinetics at endocardial than epicardial
      stimulation sites. Flecainide, a Na(+) channel blocker, reduced the maximal ERP
      restitution slope, slowed restitution kinetics, and eliminated epicardial-to
      endocardial difference in dynamics of electrical restitution. Greater
      excitability and steeper electrical restitution have been associated with greater
      arrhythmic susceptibility of endocardium than epicardium, as assessed by
      measuring ventricular fibrillation threshold, inducibility of tachyarrhythmias by
      rapid cardiac pacing, and the magnitude of stimulation-evoked repolarization
      alternans. In conclusion, higher Na(+) channel expression levels may contribute
      to greater excitability, steeper electrical restitution slopes and faster
      restitution kinetics, and greater susceptibility to stimulation-evoked
      tachyarrhythmias at endocardium than epicardium in the guinea pig heart.

PMID- 21186272
TI  - Activation of the neuregulin/ErbB system during physiological ventricular
      remodeling in pregnancy.
AB  - The neuregulin-1 (NRG1)/ErbB system has emerged as a paracrine endothelium
      controlled system in the heart, which preserves left ventricular (LV) performance
      in pathophysiological conditions. Here, we analyze the activity and function of
      this system in pregnancy, which imparts a physiological condition of LV
      hemodynamic overload. NRG1 expression and ErbB receptor activation were studied
      by Western blot analyses in rats and mice at different stages of pregnancy. LV
      performance was evaluated by transthoracic echocardiography, and myocardial
      performance was assessed from twitches of isolated papillary muscles. NRG1/ErbB
      signaling was inhibited by oral treatment of animals with the dual ErbB1/ErbB2
      tyrosine kinase inhibitor lapatinib. Analyses of LV tissue revealed that protein
      expression of different NRG1 isoforms and levels of phosphorylated ErbB2 and
      ErbB4 significantly increased after 1-2 wk of pregnancy. Lapatinib prevented
      phosphorylation of ErbB2 and ERK1/2, but not of ErbB4 and protein kinase B (Akt),
      revealing that lapatinib only partially inhibited NRG1/ErbB signaling in the LV.
      Lapatinib did not prevent pregnancy-induced changes in LV mass and did not cause
      apoptotic cell death or fibrosis in the LV. Nevertheless, lapatinib led to
      premature maternal death of ~25% during pregnancy and it accentuated pregnancy
      induced LV dilatation, significantly reduced LV fractional shortening, and
      induced abnormalities of twitch relaxation (but not twitch amplitude) of isolated
      papillary muscles. This is the first study showing that the NRG1/ErbB system is
      activated, and plays a modulatory role, during physiological hemodynamic overload
      associated with pregnancy. Inhibiting this system during physiological overload
      may cause LV dysfunction in the absence of myocardial cell death.

PMID- 21186270
TI  - Catechin treatment improves cerebrovascular flow-mediated dilation and learning
      abilities in atherosclerotic mice.
AB  - Severe dyslipidemia and the associated oxidative stress could accelerate the age
      related decline in cerebrovascular endothelial function and cerebral blood flow
      (CBF), leading to neuronal loss and impaired learning abilities. We hypothesized
      that a chronic treatment with the polyphenol catechin would prevent endothelial
      dysfunction, maintain CBF responses, and protect learning abilities in
      atherosclerotic (ATX) mice. We treated ATX (C57Bl/6-LDLR(-/-)hApoB(+/+); 3 mo
      old) mice with catechin (30 mg . kg(-1) . day(-1)) for 3 mo, and C57Bl/6 [wild
      type (WT), 3 and 6 mo old] mice were used as controls. ACh- and flow-mediated
      dilations (FMD) were recorded in pressurized cerebral arteries. Basal CBF and
      increases in CBF induced by whisker stimulation were measured by optical
      coherence tomography and Doppler, respectively. Learning capacities were
      evaluated with the Morris water maze test. Compared with 6-mo-old WT mice,
      cerebral arteries from 6-mo-old ATX mice displayed a higher myogenic tone, lower
      responses to ACh and FMD, and were insensitive to NOS inhibition (P < 0.05),
      suggesting endothelial dysfunction. Basal and increases in CBF were lower in 6-mo
      old ATX than WT mice (P < 0.05). A decline in the learning capabilities was also
      observed in ATX mice (P < 0.05). Catechin 1) reduced cerebral superoxide staining
      (P < 0.05) in ATX mice, 2) restored endothelial function by reducing myogenic
      tone, improving ACh- and FMD and restoring the sensitivity to nitric oxide
      synthase inhibition (P < 0.05), 3) increased the changes in CBF during
      stimulation but not basal CBF, and 4) prevented the decline in learning abilities
      (P < 0.05). In conclusion, catechin treatment of ATX mice prevents
      cerebrovascular dysfunctions and the associated decline in learning capacities.

PMID- 21186273
TI  - Moderate exercise training provides left ventricular tolerance to acute pressure
      overload.
AB  - The present study evaluated the impact of moderate exercise training on the
      cardiac tolerance to acute pressure overload. Male Wistar rats were randomly
      submitted to exercise training or sedentary lifestyle for 14 wk. At the end of
      this period, the animals were anaesthetized, mechanically ventilated, and
      submitted to hemodynamic evaluation with biventricular tip pressure manometers.
      Acute pressure overload was induced by banding the descending aorta to induce a
      60% increase of peak systolic left ventricular pressure during 120 min. This
      resulted in the following experimental groups: 1) sedentary without banding (SED
      + Sham), 2) sedentary with banding (SED + Band), and 3) exercise trained with
      banding (EX + Band). In response to aortic banding, SED + Band animals could not
      sustain the 60% increase of peak systolic pressure for 120 min, even with
      additional narrowing of the banding. This was accompanied by a reduction of
      dP/dt(max) and dP/dt(min) and a prolongation of the time constant tau, indicating
      impaired systolic and diastolic function. This impairment was not observed in EX
      + Band (P < 0.05 vs. SED + Band). Additionally, compared with SED + Band, EX +
      Band presented less myocardial damage, exhibited attenuated protein expression of
      active caspase-3 and NF-kappaB (P < 0.016), and showed less protein carbonylation
      and nitration (P < 0.05). These findings support our hypothesis that exercise
      training has a protective role in the modulation of the early cardiac response to
      pressure overload.

PMID- 21186274
TI  - Cerebral microvascular rarefaction induced by whole brain radiation is reversible
      by systemic hypoxia in mice.
AB  - Whole brain radiation therapy (WBRT) leads to cognitive impairment in 40-50% of
      brain tumor survivors following treatment. Although the etiology of cognitive
      deficits post-WBRT remains unclear, vascular rarefaction appears to be an
      important component of these impairments. In this study, we assessed the effects
      of WBRT on the cerebrovasculature and the effects of systemic hypoxia as a
      potential mechanism to reverse the microvascular rarefaction. Transgenic mice
      expressing green fluorescent protein driven by the Acta2 (smooth muscle actin)
      promoter for blood vessel visualization were randomly assigned to control or
      radiated groups. Animals received a clinical series of 4.5 Gy WBRT two times
      weekly for 4 wk followed by 1 mo of recovery. Subsequently, mice were subjected
      to 11% (hypoxia) or 21% (normoxia) oxygen for 1 mo. Capillary density in
      subregions of the hippocampus revealed profound vascular rarefaction that
      persisted despite local tissue hypoxia. Nevertheless, systemic hypoxia was
      capable of completely restoring cerebrovascular density. Thus hippocampal
      microvascular rarefaction post-WBRT is not capable of stimulating angiogenesis
      and can be reversed by chronic systemic hypoxia. Our results indicate a potential
      shift in sensitivity to angiogenic stimuli and/or the existence of an independent
      pathway of regulating cerebral microvasculature.

PMID- 21186275
TI  - Mechanisms of novel cardioprotective functions of CCN2/CTGF in myocardial
      ischemia-reperfusion injury.
AB  - CCN2/connective tissue growth factor (CTGF), a CCN family matricellular protein
      repressed in healthy hearts after birth, is induced in heart failure of various
      etiologies. Multiple cellular and biological functions have been assigned to
      CCN2/CTGF depending on cellular context. However, the functions and mechanisms of
      action of CCN2/CTGF in the heart as well as its roles in cardiac physiology and
      pathophysiology remain unknown. Transgenic mice with cardiac-restricted
      overexpression of CTGF (Tg-CTGF) were generated and compared with nontransgenic
      littermate control (NLC) mice. Tg-CTGF mice displayed slightly lower cardiac mass
      and inconspicuous increase of myocardial collagen compared with NLC mice but no
      evidence of contractile dysfunction. Analysis of the myocardial transcriptome by
      DNA microarray revealed activation of several distinct gene programs in Tg-CTGF
      hearts involved in cardioprotection and growth inhibition. Indeed, Tg-CTGF mice
      subjected to ischemia-reperfusion injury by in situ transient occlusion of the
      left anterior descending coronary artery in vivo displayed reduced vulnerability
      with markedly diminished infarct size. These findings were recapitulated in
      isolated hearts perfused with recombinant human (h)CTGF before the ischemia
      reperfusion procedure. Consistently, Tg-CTGF hearts, as well as isolated adult
      cardiac myocytes exposed to recombinant hCTGF, displayed enhanced phosphorylation
      and activity of the Akt/p70S6 kinase/GSK-3beta salvage kinase pathway and
      induction of several genes with reported cardioprotective functions. Inhibition
      of Akt activities also prevented the cardioprotective phenotype of hearts from Tg
      CTGF mice. This report provides novel evidence that CTGF confers cardioprotection
      by salvage phosphokinase signaling leading to inhibition of GSK-3beta activities,
      activation of phospho-SMAD2, and reprogramming of gene expression.

PMID- 21186277
TI  - Promoting a central role for physiology in research and education worldwide.

PMID- 21186276
TI  - Endogenous HMGB1 contributes to ischemia-reperfusion-induced myocardial apoptosis
      by potentiating the effect of TNF-&alpha;/JNK.
AB  - High-mobility group box 1 (HMGB1) is a nuclear protein that has been implicated
      in the myocardial inflammation and injury induced by ischemia-reperfusion (I/R).
      The purpose of the present study was to assess the role of HMGB1 in myocardial
      apoptosis induced by I/R. In vivo, myocardial I/R induced an increase in
      myocardial HMGB1 expression and apoptosis. Inhibition of HMGB1 (A-box)
      ameliorated the I/R-induced myocardial apoptosis. In vitro, isolated cardiac
      myocytes were challenged with anoxia-reoxygenation (A/R; in vitro correlate to
      I/R). A/R-challenged myocytes also generated HMGB1 and underwent apoptosis.
      Inhibition of HMGB1 attenuated the A/R-induced myocyte apoptosis. Exogenous HMGB1
      had no effect on myocyte apoptosis. However, inhibition of HMGB1 attenuated
      myocyte TNF-alpha production after the A/R was challenged; surprisingly, HMGB1
      itself did not induce myocyte TNF-alpha production. Exogenous TNF-alpha induced a
      moderate proapoptotic effect on the myocytes, an effect substantially potentiated
      by coadministration of HMGB1. It is generally accepted that apoptosis induced by
      TNF-alpha is regulated by the balance of activation of c-Jun NH(2)-terminal
      kinase (JNK) and NF-kappaB. Indeed, in the present study, TNF-alpha increased the
      phosphorylation status of JNK and p65, a subunit of NF-kappaB; HMGB1 greatly
      potentiated TNF-alpha-induced JNK phosphorylation. Furthermore, inhibition of JNK
      (SP-600125) prevented the myocyte apoptosis induced by a TNF-alpha/HMGB1
      cocktail. Finally, A/R increased HMGB1 production in both wild-type and toll-like
      receptor 4-deficient myocytes; however, deficiency in toll-like receptor 4
      diminished A/R-induced myocyte apoptosis, TNF-alpha, and JNK activation. Our
      results indicate that myocyte-derived HMGB1 and TNF-alpha work in concert to
      promote I/R-induced myocardial apoptosis through JNK activation.

PMID- 21186279
TI  - Peroxisome biogenesis: something old, something new, something borrowed.
AB  - Eukaryotic cells are characterized by their varied complement of organelles. One
      set of membrane-bound, usually spherical compartments are commonly grouped
      together under the term peroxisomes. Peroxisomes function in regulating the
      synthesis and availability of many diverse lipids by harnessing the power of
      oxidative reactions and contribute to a number of metabolic processes essential
      for cellular differentiation and organismal development.

PMID- 21186278
TI  - Olfactory learning in Drosophila.
AB  - Studies of olfactory learning in Drosophila have provided key insights into the
      brain mechanisms underlying learning and memory. One type of olfactory learning,
      olfactory classical conditioning, consists of learning the contingency between an
      odor with an aversive or appetitive stimulus. This conditioning requires the
      activity of molecules that can integrate the two types of sensory information,
      the odorant as the conditioned stimulus and the aversive or appetitive stimulus
      as the unconditioned stimulus, in brain regions where the neural pathways for the
      two stimuli intersect. Compelling data indicate that a particular form of
      adenylyl cyclase functions as a molecular integrator of the sensory information
      in the mushroom body neurons. The neuronal pathway carrying the olfactory
      information from the antennal lobes to the mushroom body is well described.
      Accumulating data now show that some dopaminergic neurons provide information
      about aversive stimuli and octopaminergic neurons about appetitive stimuli to the
      mushroom body neurons. Inhibitory inputs from the GABAergic system appear to gate
      olfactory information to the mushroom bodies and thus control the ability to
      learn about odors. Emerging data obtained by functional imaging procedures
      indicate that distinct memory traces form in different brain regions and
      correlate with different phases of memory. The results from these and other
      experiments also indicate that cross talk between mushroom bodies and several
      other brain regions is critical for memory formation.

PMID- 21186280
TI  - TMEM16A protein: a new identity for Ca(2+)-dependent Cl- channels.
AB  - Ca(+)-dependent Cl- channels (CaCCs) play a variety of physiological roles in
      different organs and tissues, including transepithelial Cl- secretion, smooth
      muscle contraction, regulation of neuronal excitability, and transduction of
      sensory stimuli. The recent identification of TMEM16A protein as an important
      component of CaCCs should allow a better understanding of their physiological
      role, structure-function relationship, and regulatory mechanisms.

PMID- 21186281
TI  - Hijacking solute carriers for proton-coupled drug transport.
AB  - The physiological role of mammalian solute carrier (SLC) proteins is to mediate
      transmembrane movement of electrolytes, nutrients, micronutrients, vitamins, and
      endogenous metabolites from one cellular compartment to another. Many
      transporters in the small intestine, kidney, and solid tumors are H(+)-coupled,
      driven by local H(+)-electrochemical gradients, and transport numerous drugs.
      These transporters include PepT1 and PepT2 (SLC15A1/2), PCFT (SLC46A1), PAT1
      (SLC36A1), OAT10 (SLC22A13), OATP2B1 (SLCO2B1), MCT1 (SLC16A1), and MATE1 and
      MATE2-K (SLC47A1/2).

PMID- 21186282
TI  - Comparison of open three-field and minimally-invasive esophagectomy for
      esophageal cancer.
AB  - The aim was to compare the early outcomes between thoracoscopic and laparoscopic
      esophagectomy (TLE) and open three-field esophagectomy for esophageal cancer. We
      retrospectively analyzed clinical data from 96 patients with esophageal cancer
      who underwent TLE, and 78 patients who underwent open three-field esophagectomy
      from March 2008 to September 2010. All the operations were successful. There was
      no significant difference between TLE and open three-field esophagectomy with
      regard to the number of lymph nodes procured (17.75+/-5.56 vs. 18.03+/-6.20,
      P>0.05), complications (32.3% vs. 46.2%, P>0.05), and operative mortality (2.1%
      vs. 3.8%, P>0.05). However, hospital stay was significantly shorter in the TLE
      group than the open esophagectomy group (12.64+/-8.82 vs. 17.53+/-6.40 days,
      P<0.01), and the TLE group had significantly less blood loss (346.68+/-41.13 vs.
      519.26+/-47.74 ml, P<0.01). This showed that TLE for esophageal cancer offers
      results as good as or better than those with open three-field esophagectomy.

PMID- 21186283
TI  - Effects of foam or gauze on sternum wound contraction, distension and heart and
      lung damage during negative-pressure wound therapy of porcine sternotomy wounds.
AB  - The study was performed to compare the effects of negative-pressure wound therapy
      (NPWT) using gauze and foam on wound edge movement and the macroscopic appearance
      of the heart and lungs after NPWT. Sternotomy wounds were created in 6*70 kg
      pigs. Negative pressures of -40, -70, -120 and -160 mmHg were applied and the
      following were evaluated: wound contraction, distension and the macroscopic
      appearance of the heart and lungs after NPWT. Wound contraction was greater when
      using foam than gauze (3.5+/-0.3 cm and 1.3+/-0.2 cm, respectively, P<0.01). The
      application of traction to the lateral edges of the sternotomy resulted in
      greater wound distention with foam than with gauze (5.3+/-0.3 cm and 3.6+/-0.2
      cm, respectively, P<0.001). After using foam, the surface of the heart was red
      and mottled, and lung emphysema and sometimes, lung rupture were observed. After
      using gauze, the organ surface had no markings. The study shows that foam allows
      greater wound contraction and distension than gauze. This movement of the wound
      edges may cause damage to the underlying organs. There is less damage to the
      heart and lungs when using gauze than foam.

PMID- 21186284
TI  - Is brain natriuretic peptide a marker for adverse postoperative outcomes in
      patients undergoing cardiac surgery?
AB  - A best evidence topic (BET) was constructed according to a structured protocol.
      The question addressed was 'Is brain natriuretic peptide (BNP) a marker for
      adverse postoperative outcomes in patients undergoing cardiac surgery?' Nearly
      200 papers were found using the reported search, of which 17 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. BNP levels have been shown by several prospective
      observational cohort studies to be a marker for cardiac dysfunction and adverse
      outcome in patients undergoing cardiac surgery. BNP levels can be used to guide
      the therapy of patients with heart failure which may reduce adverse cardiac
      events. Whether BNP-guided therapy can be applied to patients undergoing cardiac
      surgery is unknown. We conclude that preoperative and postoperative measurement
      of natriuretic peptides could help predict postoperative cardiac dysfunction and
      adverse outcome in patients undergoing cardiac surgery. Furthermore, they may
      improve the ability of commonly used risk assessment tools to predict outcome.

PMID- 21186285
TI  - N-Glycans mutations rule oligomeric assembly and functional expression of P2X3
      receptor for extracellular ATP.
AB  - N-Glycosylation affects the function of ion channels at the level of multisubunit
      assembly, protein trafficking, ligand binding and channel opening. Like the
      majority of membrane proteins, ionotropic P2X receptors for extracellular ATP are
      glycosylated in their extracellular moiety. Here, we used site-directed
      mutagenesis to the four predicted N-glycosylation sites of P2X(3) receptor
      (Asn(139), Asn(170), Asn(194) and Asn(290)) and performed comparative analysis of
      the role of N-glycans on protein stability, plasma membrane delivery, trimer
      formation and inward currents. We have found that in transiently transfected
      HEK293 cells, Asn(170) is apparently the most important site for receptor
      stability, since its mutation causes a primary loss in protein content and
      indirect failure in membrane expression, oligomeric association and inward
      current responses. Even stronger effects are obtained when mutating Thr(172) in
      the same glycosylation consensus. Asn(194) and Asn(290) are the most dispensable,
      since even their simultaneous mutation does not affect any tested receptor
      feature. All double mutants containing Asn(170) mutation or the Asn(139)/Asn(290)
      double mutant are instead almost unable to assemble into a functional trimeric
      structure. The main emerging finding is that the inability to assemble into
      trimers might account for the impaired function in P2X(3) mutants where residue
      Asn(170) is replaced. These results improve our knowledge about the role of N
      glycosylation in proper folding and oligomeric association of P2X(3) receptor.

PMID- 21186286
TI  - A potential biochemical mechanism underlying the influence of sterol deprivation
      stress on Caenorhabditis elegans longevity.
AB  - To investigate the biochemical mechanism underlying the effect of sterol
      deprivation on longevity in Caenorhabditis elegans, we treated parent worms (P0)
      with 25-azacoprostane (Aza), which inhibits sitosterol-to-cholesterol conversion,
      and measured mean lifespan (MLS) in F2 worms. At 25 MUM (~EC(50)), Aza reduced
      total body sterol by 82.5%, confirming sterol depletion. Aza (25 MUM) treatment
      of wild-type (N2) C. elegans grown in sitosterol (5 MUg/ml) reduced MLS by 35%.
      Similar results were obtained for the stress-related mutants daf-16(mu86) and gas
      1(fc21). Unexpectedly, Aza had essentially no effect on MLS in the stress
      resistant daf-2(e1370) or mitochondrial complex II mutant mev-1(kn1) strains,
      indicating that Aza may target both insulin/IGF-1 signaling (IIS) and
      mitochondrial complex II. Aza increased reactive oxygen species (ROS) levels 2.7
      fold in N2 worms, but did not affect ROS production by mev-1(kn1), suggesting a
      direct link between Aza treatment and mitochondrial ROS production. Moreover,
      expression of the stress-response transcription factor SKN-1 was decreased in
      amphid neurons by Aza and that of DAF-28 was increased when DAF-6 was involved,
      contributing to lifespan reduction.

PMID- 21186287
TI  - Erwinia oleae sp. nov., isolated from olive knots caused by Pseudomonas
      savastanoi pv. savastanoi.
AB  - Three endophytic bacterial isolates were obtained in Italy from olive knots
      caused by Pseudomonas savastanoi pv. savastanoi. Phenotypic tests in combination
      with 16S rRNA gene sequence analysis indicated a phylogenetic position for these
      isolates in the genera Erwinia or Pantoea, and revealed two other strains with
      highly similar 16S rRNA gene sequences (>99 %), CECT 5262 and CECT 5264, obtained
      in Spain from olive knots. Rep-PCR DNA fingerprinting of the five strains from
      olive knots with BOX, ERIC and REP primers revealed three groups of profiles that
      were highly similar to each other. Multilocus sequence analysis (MLSA) based on
      concatenated partial atpD, gyrB, infB and rpoB gene sequences indicated that the
      strains constituted a single novel species in the genus Erwinia. The strains
      showed general phenotypic characteristics typical of the genus Erwinia and whole
      genome DNA-DNA hybridization data confirmed that they represented a single novel
      species of the genus Erwinia. The strains showed DNA G+C contents ranging from
      54.7 to 54.9 mol%. They could be discriminated from phylogenetically related
      species of the genus Erwinia by their ability to utilize potassium gluconate, l
      rhamnose and d-arabitol, but not glycerol, inositol or d-sorbitol. The name
      Erwinia oleae sp. nov. (type strain DAPP-PG 531(T)= LMG 25322(T) = DSM 23398(T))
      is proposed for this novel taxon.

PMID- 21186288
TI  - Nonomuraea maritima sp. nov., isolated from coastal sediment.
AB  - A novel actinomycete, strain FXJ7.203(T), was isolated from a coastal sediment
      sample collected in Bohai Bay, China. In 16S rRNA gene sequence analyses, strain
      FXJ7.203(T) always formed a unique monophyletic line within the genus Nonomuraea
      and was most closely related to Nonomuraea turkmeniaca (97.9 %), Nonomuraea
      candida (97.8 %), Nonomuraea helvata (97.7 %) and Nonomuraea rubra (97.5 %).
      Morphological and chemotaxonomic characteristics supported the allocation of the
      strain to the genus Nonomuraea. The polar lipid profile showed that its
      phospholipid type was PIV. The major fatty acids were iso-C(16 : 0), C(17 :
      1)omega6c, iso-C(16 : 1) G, 10-methyl C(17 : 0) and iso-C(15 : 0). The major
      menaquinone was MK-9(H(4)) with minor amounts of MK-9(H(2)), MK-9(H(0)) and MK
      9(H(6)). The results of physiological and biochemical tests allowed
      differentiation of strain FXJ7.203(T) from closely related species. Based on the
      genotypic and phenotypic data, strain FXJ7.203(T) represents a novel species of
      the genus Nonomuraea, for which the name Nonomuraea maritima sp. nov. is
      proposed, with strain FXJ7.203(T) ( = CGMCC 4.5681(T) = NBRC 106687(T)) as the
      type strain.

PMID- 21186289
TI  - Flavobacterium chungbukense sp. nov., isolated from soil.
AB  - A yellow-pigmented, Gram-staining-negative, non-motile, strictly aerobic and rod
      shaped bacterium, designated CS100(T), was isolated from soil in Chungbuk, Korea.
      Phylogenetic analysis and comparative studies based on the 16S rRNA gene sequence
      showed that strain CS100(T) belonged to the genus Flavobacterium in the family
      Flavobacteriaceae. Strain CS100(T) showed the highest sequence similarities to
      Flavobacterium glaciei JCM 13953(T) (97.6 %) and Flavobacterium johnsoniae KACC
      11410(T) (97.1 %). Sequence similarity to other members of the genus
      Flavobacterium was 91.5-97.0 %. Growth occurred at 4-30  degrees C, at pH 5.0-9.0
      and in the presence of 0-2 % (w/v) NaCl. Flexirubin-type pigments were produced.
      Menaquinone-6 (MK-6) was the major respiratory quinone and the major fatty acids
      were iso-C(15 : 0) (17.3 %), summed feature 3 (comprising iso-C(15 : 0) 2-OH
      and/or C(16 : 1)omega7c, 15.5 %) and C(16 : 0) (11.8 %). The DNA G+C content was
      36.4 mol%. Strain CS100(T) hydrolysed skimmed milk and gelatin, but not chitin or
      pectin, and showed oxidase and catalase activities. DNA-DNA relatedness was 3.0 %
      with F. glaciei JCM 13953(T) and 11.5 % with F. johnsoniae KACC 11410(T). On the
      basis of the evidence from this study, strain CS100(T) represents a novel species
      of the genus Flavobacterium, for which the name Flavobacterium chungbukense sp.
      nov. is proposed. The type strain is CS100(T) ( = KACC 15048(T) = JCM 17386(T)).

PMID- 21186290
TI  - Flavobacterium phragmitis sp. nov., an endophyte of reed (Phragmites australis).
AB  - A Gram-staining-negative bacterium, designated strain BLN2(T), was isolated from
      within the roots of reeds (Phragmites australis) in Beijing Cuihu Wetland (China)
      and characterized using a polyphasic taxonomic approach. The cells were yellow
      pigmented, rod-shaped, strictly aerobic and devoid of flagella, but showed
      gliding motility. Strain BLN2(T) produced yellow, translucent, circular and
      convex colonies, with optimal growth at 30  degrees C and pH 7.0. The major
      respiratory quinone was menaquinone 6 (MK-6) and the predominant fatty acids were
      iso-C(15 : 0), summed feature 3 (comprising C(16 : 1)omega7c and/or C(16 :
      1)omega6c), C(16 : 0) 3-OH, C(16 : 0,) iso-C(17 : 0) 3-OH and iso-C(15 : 0) 3-OH.
      The G+C content of the genomic DNA was 34.8 mol%. The 16S rRNA gene sequence
      analysis showed that strain BLN2(T) belonged to the genus Flavobacterium and was
      most closely related to Flavobacterium anhuiense CGMCC 1.6859(T) (97.0 % sequence
      similarity). The DNA-DNA relatedness between strain BLN2(T) and F. anhuiense
      CGMCC 1.6859(T) was 25.7 %. Based on the phenotypic data and phylogenetic
      inference presented, it is concluded that strain BLN2(T) represents a novel
      species within the genus Flavobacterium, for which the name Flavobacterium
      phragmitis sp. nov. is proposed. The type strain is BLN2(T) ( = DSM 23314(T) =
      CGMCC 1.10370(T)).

PMID- 21186291
TI  - Luteimonas lutimaris sp. nov., isolated from a tidal flat.
AB  - A Gram-staining-negative, strictly aerobic bacterium, designated strain G3(T),
      was isolated from a tidal flat of the Taean coast in South Korea. Cells were
      moderately halotolerant and non-motile rods showing catalase- and oxidase
      positive reactions. Growth of strain G3(T) was observed between 15 and 40 
      degrees C (optimum 30  degrees C) and between pH 5.5 and 9.0 (optimum pH 6.5
      7.5). Strain G3(T) contained Q-8 as the predominant lipoquinone and iso-C(15 :
      0), iso-C(17 : 1)omega9c, iso-C(16 : 0) and iso-C(11 : 0) as the major fatty
      acids. The G+C content of the genomic DNA was 69.6 mol%. Phylogenetic analyses
      based on 16S rRNA gene sequences showed that strain G3(T) formed a tight
      phylogenetic lineage with Luteimonas mephitis B1953/27.1(T) within the genus
      Luteimonas and was most closely related to L. mephitis B1953/27.1(T) with 98.0 %
      16S rRNA gene sequence similarity. The DNA-DNA relatedness between strain G3(T)
      and L. mephitis B1953/27.1(T) was 35.2 +/- 3.3 %. On the basis of chemotaxonomic
      data and molecular properties, strain G3(T) represents a novel species of the
      genus Luteimonas, for which the name Luteimonas lutimaris sp. nov. is proposed.
      The type strain is G3(T) (= KACC 14929(T) = JCM 16916(T)).

PMID- 21186292
TI  - Terriglobus saanensis sp. nov., an acidobacterium isolated from tundra soil.
AB  - Two aerobic bacterial strains, designated SP1PR4(T) and SP1PR5, were isolated
      from tundra soil samples collected from Saana fjeld, North-western Finland (69
      degrees  03' N 20 degrees  50' E). Cells of both strains were Gram-negative, non
      motile rods. Phylogenetic analysis indicated that the strains belong to the genus
      Terriglobus in subdivision 1 of the phylum Acidobacteria. Strains SP1PR4(T) and
      SP1PR5 shared identical BOX and ERIC fingerprints and 99.7 % 16S rRNA gene
      similarity indicating that, together with their identical physiological features,
      these strains are members of the same species. The 16S rRNA gene sequence
      similarity of SP1PR4(T) and SP1PR5 with Terriglobus roseus DSM 18391(T) was 97.1
      %. A low DNA-DNA hybridization value (<20 %) and rpoB gene sequence similarity
      (83.6 %) with T. roseus DSM 18391(T) indicated that the tundra soil isolates
      represent novel members of the genus Terriglobus. Strains SP1PR4(T) and SP1PR5
      grew at pH 4.5-7.5 and 4-30  degrees C. Sugars were the preferred growth
      substrates. The major cellular fatty acids were iso-C(15 : 0), C(16 : 1)omega7c,
      iso-C(13 : 0) and C(16 : 0). The DNA G+C content of strain SP1PR4(T) was 57.3
      mol%. Based on phylogenetic, chemotaxonomic and physiological analyses, the name
      Terriglobus saanensis sp. nov. is proposed to accommodate the two strains; the
      type strain is SP1PR4(T) ( = DSM 23119(T)  = ATCC BAA-1853(T)).

PMID- 21186293
TI  - Reclassification of Aurantimonas altamirensis (Jurado et al. 2006), Aurantimonas
      ureilytica (Weon et al. 2007) and Aurantimonas frigidaquae (Kim et al. 2008) as
      members of a new genus, Aureimonas gen. nov., as Aureimonas altamirensis gen.
      nov., comb. nov., Aureimonas ureilytica comb. nov. and Aureimonas frigidaquae
      comb. nov., and emended descriptions of the genera Aurantimonas and Fulvimarina.
AB  - Members of the genera Aurantimonas and Fulvimarina have largely been described on
      the basis of 16S rRNA gene sequence analyses, biochemical tests and limited
      chemotaxonomic data. Examination of the polar lipid compositions of members of
      these two genera indicated that although the patterns were similar with regards
      the phospholipid and amino lipid compositions, there were clear differences in
      the presence or absence of the glycolipid sulfoquinovosyldiacylglycerol (SQDG).
      This glycolipid was absent in members of the species Aurantimonas coralicida and
      Fulvimarina pelagi but was present in Aurantimonas altamirensis, Aurantimonas
      ureilytica and Aurantimonas frigidaquae. These results are also consistent with
      the 16S rRNA sequence-based grouping. We therefore propose that the genus
      Aurantimonas be divided further to reflect this additional information. Thus, it
      is recommended that Aurantimonas altamirensis, Aurantimonas ureilytica and
      Aurantimonas frigidaquae are transferred to a new genus, Aureimonas gen. nov., as
      Aureimonas altamirensis gen. nov., comb. nov. (type strain S21B(T) = CECT 7138(T)
      = CIP 109525(T) = KCTC 22106(T) = LMG 23375(T) = DSM 21988(T)), Aureimonas
      ureilytica comb. nov. (type strain 5715S-12(T) = KACC 11607(T) = DSM 18598(T) =
      CIP 109815(T)) and Aureimonas frigidaquae comb. nov. (type strain CW5(T) = KCTC
      12893(T) = JCM 14755(T) = DSM 21987(T)). The type species of the new genus is
      Aureimonas altamirensis. Additionally, emended descriptions of the genera
      Aurantimonas and Fulvimarina are provided.

PMID- 21186294
TI  - Comment on the Importance of S100A4 in regulation of MMP-13.

PMID- 21186296
TI  - The C terminus of Alb3 interacts with the chromodomains 2 and 3 of cpSRP43.

PMID- 21186299
TI  - Hedgehog signaling and therapeutics in pancreatic cancer.
AB  - OBJECTIVE: To conduct a systematic review of the role that the hedgehog signaling
      pathway has in pancreatic cancer tumorigenesis. METHOD: PubMed search (2000-2010)
      and literature based references. RESULTS: Firstly, in 2009 a genetic analysis of
      pancreatic cancers found that a core set of 12 cellular signaling pathways
      including hedgehog were genetically altered in 67-100% of cases. Secondly, in
      vitro and in vivo studies of treatment with cyclopamine (a naturally occurring
      antagonist of the hedgehog signaling pathway component; Smoothened) has shown
      that inhibition of hedgehog can abrogate pancreatic cancer metastasis. Thirdly,
      experimental evidence has demonstrated that sonic hedgehog (Shh) is correlated
      with desmoplasia in pancreatic cancer. This is important because targeting the
      Shh pathway potentially may facilitate chemotherapeutic drug delivery as
      pancreatic cancers tend to have a dense fibrotic stroma that extrinsically
      compresses the tumor vasculature leading to a hypoperfusing intratumoral
      circulation. It is probable that patients with locally advanced pancreatic cancer
      will derive the greatest benefit from treatment with Smoothened antagonists.
      Fourthly, it has been found that ligand dependent activation by hedgehog occurs
      in the tumor stromal microenvironment in pancreatic cancer, a paracrine effect on
      tumorigenesis. Finally, in pancreatic cancer, cells with the CD44+CD24+ESA+
      immunophenotype select a population enriched for cancer initiating stem cells.
      Shh is increased 46-fold in CD44+CD24+ESA+ cells compared with normal pancreatic
      epithelial cells. Medications that destruct pancreatic cancer initiating stem
      cells are a potentially novel strategy in cancer treatment. CONCLUSIONS: Aberrant
      hedgehog signaling occurs in pancreatic cancer tumorigenesis and therapeutics
      that target the transmembrane receptor Smoothened abrogate hedgehog signaling and
      may improve the outcomes of patients with pancreatic cancer.

PMID- 21186298
TI  - Aberrant DNA hypermethylation patterns lead to transcriptional silencing of tumor
      suppressor genes in UVB-exposed skin and UVB-induced skin tumors of mice.
AB  - Overexposure of the human skin to solar ultraviolet (UV) radiation is the major
      etiologic factor for development of skin cancers. Here, we report the results of
      epigenetic modifications in UV-exposed skin and skin tumors in a systematic
      manner. The skin and tumor samples were collected after chronic exposure of the
      skin of SKH-1 hairless mice to UVB radiation using a well-established
      photocarcinogenesis protocol. We found a distinct DNA hypermethylation pattern in
      the UVB-exposed epidermal skin and UVB-induced skin tumors that was associated
      with the elevated expression and activity of the DNA methyltransferases (Dnmt) 1,
      Dnmt3a and Dnmt3b. To explore the role of hypermethylation in skin
      photocarcinogenesis, we focused on the p16(INK4a) and RASSF1A tumor suppressor
      genes, which are transcriptionally silenced on methylation. We established that
      the silencing of these genes in UVB-exposed epidermis and UVB-induced skin tumors
      is associated with a network of epigenetic modifications, including
      hypoacetylation of histone H3 and H4 and increased histone deacetylation, as well
      as recruitment of methyl-binding proteins, including MeCP2 and MBD1, to the
      methylated CpGs. Higher levels of DNA methylation and DNMT activity in human
      squamous cell carcinoma specimens than in normal human skin suggest that the data
      are relevant clinically. Our data indicate for the first time that UVB-induced
      DNA hypermethylation, enhanced Dnmt activity and histone modifications occur in
      UVB-exposed skin and UVB-induced skin tumors and suggest that these events are
      involved in the silencing of tumor suppressor genes and in skin tumor
      development.

PMID- 21186301
TI  - Neuropilin-1 exerts co-receptor function for TGF-beta-1 on the membrane of cancer
      cells and enhances responses to both latent and active TGF-beta.
AB  - Neuropilin (Nrp)-1 and Nrp-2 are multifunctional proteins frequently expressed by
      cancer cells and contribute to tumor progression by mechanisms that are not well
      understood. They are co-receptors for vascular endothelial growth factor and
      class 3 semaphorins, but recently we found that Nrp1 also binds latent and active
      transforming growth factor (TGF)-beta1, and activates the latent form latency
      associated peptide (LAP)-TGF-beta1. Here, we report that Nrp1 has affinity for
      TGF-beta receptors TbetaRI and TbetaRII, the signaling TGF-beta receptors, as
      well as TbetaRIII (betaglycan), as determined in binding assays, pull down assays
      and confocal microscopy. Nrp1 had a higher affinity for TbetaRI than TbetaRII and
      could form a complex with these receptors. In breast cancer cells, Nrp1 and
      TbetaRI cointernalized in the presence of TGF-beta1. Nrp1 acted as a TGF-beta co
      receptor by augmenting canonical Smad2/3 signaling. Importantly, Nrp-positive
      cancer cells, unlike negative cells, were able to activate latent TGF-beta1 and
      respond. We examined two other membrane proteins that bind LAP-TGF-beta, i.e. an
      RGD-binding integrin (alphavbeta3) and Glycoprotein A repetitions predominant
      (CLRRC32). RGD-binding integrins are frequently expressed by cancer cells, and
      glycoprotein A repetitions predominant is expressed by activated regulatory T
      cells that appear linked to poor tumor immunity. In vitro, these receptors did
      not activate LAP-TGF-beta1, but subsequent addition of Nrp1 activated the
      cytokine. Thus, Nrp1 might collaborate with other latent TGF-beta receptors in
      TGF-beta capture and activation. We also show that Nrp2 has activities similar to
      Nrp1. We conclude that Nrp1 is a co-receptor for TGF-beta1 and augments responses
      to latent and active TGF-beta. Since TGF-beta promotes metastasis this is highly
      relevant to cancer biology.

PMID- 21186300
TI  - Chemopreventive effects of early-stage and late-stage supplementation of vitamin
      E and selenium on esophageal carcinogenesis in rats maintained on a low vitamin
      E/selenium diet.
AB  - Low vitamin E and selenium (Ve/Se) nutritional status is known to be associated
      with increased risk of esophageal squamous cell carcinoma (ESCC). A previous
      human intervention trial demonstrated that Ve/Se supplementation decreased the
      occurrence of esophageal cancer death among younger participants but not among
      older ones. In this study, we intended to mimic this human nutritional status to
      determine the chemopreventive effects of Ve/Se supplementation at the early or
      late stage of esophageal carcinogenesis in rats maintained on a low Ve/Se diet.
      ESCC was induced in F344 rats with N-nitrosomethylbenzylamine (NMBzA) (0.35 mg/kg
      body wt, subcutaneously, three times per week for 5 weeks). The rats were
      maintained on a modified AIN-93M diet with low levels of Ve/Se or supplementation
      to the normal level by using the AIN-93M diet. At Week 25, the numbers of visible
      tumors and ESCC were significantly lower in rats on AIN-93M diet during the
      entire experimental period (Group D) or during the early stage (Group B) but not
      during the late stage (Group C). Ve/Se supplementation (switching from the low
      Ve/Se diet to the AIN-93M diet) also decreased cell proliferation, angiogenesis,
      8-hydroxy-2'-deoxyguanosine, biosynthesis of prostaglandin E2 and leukotriene B4,
      expression of cyclooxygenase 2 and 5-lipoxygenase in the esophagus. Our results
      demonstrated that Ve/Se supplementation inhibited NMBzA-induced esophageal
      carcinogenesis in rats on low Ve/Se diet, and supplementation during the early
      stage is more effective than during the late stage of carcinogenesis.

PMID- 21186304
TI  - Bracket slot and archwire dimensions: manufacturing precision and third order
      clearance.
AB  - OBJECTIVE: To determine the accuracy of different manufacturer's dimensions of
      bracket slots and stainless steel archwires and compare these against the
      tolerance limits given by DIN 13971 and 13971-2. Further to calculate torque play
      and effective torque and to compare the results to nominal torque. DESIGN: A
      laboratory investigation. SETTING: The Department of Orthodontics and Dentofacial
      Orthopedics at Medical University of Graz, Austria. MATERIALS AND METHODS: Ten
      upper central incisor brackets (0.022 inch) from five different bracket systems
      were investigated. Bracket slot height was measured with leaf gauges. The height
      and width of 10 stainless steel archwires with dimensions either 0.019*0.022 or
      0.020*0.025 inch were measured using a micrometer. RESULTS: All measured bracket
      slot heights were within the upper and lower tolerance limits given by DIN 13971
      2. Archwires showed measurements outside the upper and lower tolerance limits
      given by DIN 13971. The smallest effective torque loss (4.5 degrees ) resulted
      from the combination of the 0.022-inch SPEED System bracket with the 0.020*0.025
      inch SPEED Wire small upper. The highest torque loss (11.7 degrees ) was found
      with the 0.022-inch Damon 2 bracket and the 0.019*0.025-inch ECO Charge 1
      archwire. CONCLUSION: The accuracy of the manufacturers dimension is not to be
      taken for granted. A perfect 'finishing' still requires correction bends put in
      by the orthodontist.

PMID- 21186305
TI  - How well do reports of clinical trials in the orthodontic literature comply with
      the CONSORT statement?
AB  - OBJECTIVES: To assess whether clinical trials published in the orthodontic
      literature comply with the Consolidated Standards of Reporting Trials (CONSORT)
      statement, and whether compliance has changed over time. DESIGN: Retrospective
      study. SAMPLE: Clinical trials published in four orthodontic journals (American
      Journal of Orthodontics and Dentofacial Orthopedics, Angle Orthodontist, European
      Journal of Orthodontics, and Journal of Orthodontics) at three time points
      [1995/6 (pre-CONSORT), 2000/1 (post-CONSORT) and 2005/6 (post revised-CONSORT)].
      METHODS: Trials were scored using a 36-point checklist developed from the CONSORT
      statement. Each item on the checklist was scored as either included, not
      included, or not applicable if the trial design did not allow its inclusion. The
      proportion of trials describing randomization, allocation concealment, and
      blinding was also calculated. The mean scores were compared between time points
      and between journals. RESULTS: A total of 151 reports were included. The mean
      score was 41.5% (SD 10.3). The mean post-CONSORT score was higher than the pre
      CONSORT score (P = 0.01; WMD, 5.73; 95% CI, 1.64-9.82), and the mean post revised
      CONSORT was also higher than the pre-CONSORT score (P = 0.01; WMD, 4.44; 95% CI,
      1.02-7.87). At the post revised-CONSORT time point, the mean score in the
      journals which had adopted the CONSORT statement was higher than for those which
      had not (P<0.001; chi square, 17.78; df = 3). Reporting of randomization,
      allocation concealment and blinding was inadequate at all three time points.
      CONCLUSIONS: The reporting of clinical trials in the orthodontic literature has
      improved since the publication of the CONSORT statement, particularly in journals
      which have adopted the statement. However, the reporting of randomization,
      allocation concealment and blinding remains inadequate.

PMID- 21186306
TI  - How to...mechanically erupt a palatal canine.
AB  - Management of ectopic permanent maxillary canines represents one of the greatest
      challenges to orthodontists. This paper outlines a variety of techniques and
      mechanics which may facilitate expedient, predictable and safe eruption of
      palatal canines. While each method may be useful in isolation, the varying
      presentations of palatal canines ensure that the ability to apply an array of
      techniques is essential if successful outcomes are to be consistently achieved.

PMID- 21186307
TI  - Removable rapid maxillary expansion.
AB  - A novel removable rapid maxillary expansion appliance is described for use in
      routine clinical practice. The laboratory construction and clinical technique is
      described, and the advantages of the appliance over conventional rapid expansion
      devices are highlighted.

PMID- 21186308
TI  - The William Houston Gold Medal of the Royal College of Surgeons of Edinburgh
      2009.
AB  - As part of the Membership in Orthodontics examination, candidates are required to
      present five treated cases. Two of the cases treated by one of the winners of the
      William Houston Gold Medal from the MOrth diet of the Royal College of Surgeons
      of Edinburgh in 2009 are described.

PMID- 21186309
TI  - What information should we give to our orthognathic patients?
AB  - In 2002, whilst the author was an orthodontic registrar, she underwent a
      bimaxillary osteotomy to correct her class III malocclusion. This therefore gives
      her a unique perspective into the information she believes prospective patients
      undergoing similar procedures would find helpful and the choices of format to
      deliver that advice.

PMID- 21186310
TI  - Orthodontic therapists--a challenge for the 21st century.
AB  - The introduction of orthodontic therapists in 2007 has led to significant changes
      to the delivery of orthodontic treatment in the UK. This article outlines the
      author's experience of training therapists on the Yorkshire Orthodontic Therapy
      Course and discusses challenges faced by this new way of providing orthodontics
      in the UK.

PMID- 21186315
TI  - Challenges for improving patients' experiences of health care.

PMID- 21186313
TI  - Ectopia or concomitant hypohyperdontia?

PMID- 21186316
TI  - Health care reform in the Netherlands: the fairest of all?

PMID- 21186318
TI  - Identifying poorly performing general practices in England: a longitudinal study
      using data from the quality and outcomes framework.
AB  - OBJECTIVE: to determine the characteristics of general practices which perform
      poorly in terms of Quality and Outcome (QOF) performance indicators in England's
      NHS. METHOD: retrospective, four year longitudinal study, 2005 to 2008. Data were
      obtained from 8515 practices (99% of practices in England) in year 1, 8264 (98%)
      in year 2, 8192 (98%) in year 3 and 8256 (99%) in year 4. OUTCOME MEASURES: QOF
      performance scores; social deprivation (IMD-2007) and ethnicity from the 2001
      national census; general practice characteristics. RESULTS: we identified a
      cohort of 212 (2.7%) practices which remained in the lowest decile for total QOF
      scores in the four years following the introduction of the QOF. A total of
      705,386 patients were registered at these practices in year 4. These practices
      were more likely to be singlehanded (odds ratio [OR], 13.8), non-training
      practices (OR, 3.9) and located in deprived areas (OR, 2.6; most vs least
      deprived quintiles). General practitioners (GPs) in these practices were more
      often aged >= 65 years or more (OR, 7.3; mean GP age >= 65 years vs <45 years),
      male (OR 2.0), UK qualified (OR 2.0) with small list sizes (OR 3.2; list size
      <1000 vs 1500-2000 patients). We identified individual QOF indicators which were
      poorly achieved. The reported prevalence of most chronic diseases was lower in
      the poorly performing cohort. CONCLUSIONS: a small minority of practices have
      remained poor performers in terms of measurable performance indicators over a
      four-year period. The strongest predictors of poor QOF performance were
      singlehanded and small practices, and practices staffed by elderly GPs.

PMID- 21186319
TI  - Complexity in health care: a rejoinder.

PMID- 21186320
TI  - What evidence is there that a physiotherapy service in the emergency department
      improves health outcomes? A systematic review.
AB  - OBJECTIVE: the nature of care delivered in emergency departments has changed due
      to increased demand. In response, one relatively new change is the introduction
      of a physiotherapy service. There have been anecdotal reports that this may
      reduce patient waiting times and lead to more effective use of other health care
      staff, though it is unclear how such a service affects health outcomes. The
      objective was to identify the effect an emergency department physiotherapy
      service has on health outcomes. METHOD: systematic searches were carried out on
      the following databases: CINAHL, Medline, Web of Knowledge, Scopus, PEDro,
      PubMed, Cochrane and Academic Search Premier. Selection criteria included full
      text English primary studies published in peer-reviewed journals, investigating
      physiotherapy services based directly in the emergency department. Papers were
      appraised using a researcher-developed appraisal of bias tool. RESULTS: eleven
      eligible primary studies were identified. For most, the likelihood of
      methodological bias was high or unknown due to inadequate detail provided. Three
      studies were judged to have introduced little bias. At system and provider
      levels, there is insufficient evidence to support benefits of an emergency
      department physiotherapy service. At patient level, there is high-level evidence
      of benefits in terms of improved pain control and reduced disability in the short
      term. CONCLUSIONS: research evidence does not support the use of physiotherapists
      in emergency departments.

PMID- 21186322
TI  - Nontypable Haemophilus influenzae: an intracellular phase within epithelial cells
      might contribute to persistence.

PMID- 21186323
TI  - Ankyrin-B interactions with spectrin and dynactin-4 are required for dystrophin
      based protection of skeletal muscle from exercise injury.
AB  - Costameres are cellular sites of mechanotransduction in heart and skeletal muscle
      where dystrophin and its membrane-spanning partner dystroglycan distribute
      intracellular contractile forces into the surrounding extracellular matrix.
      Resolution of a functional costamere interactome is still limited but likely to
      be critical for understanding forms of muscular dystrophy and cardiomyopathy.
      Dystrophin binds a set of membrane-associated proteins (the dystrophin
      glycoprotein complex) as well as gamma-actin and microtubules and also is
      required to align sarcolemmal microtubules with costameres. Ankyrin-B binds to
      dystrophin, dynactin-4, and microtubules and is required for sarcolemmal
      association of these proteins as well as dystroglycan. We report here that
      ankyrin-B interactions with beta2 spectrin and dynactin-4 are required for
      localization of dystrophin, dystroglycan, and microtubules at costameres as well
      as protection of muscle from exercise-induced injury. Knockdown of dynactin-4 in
      adult mouse skeletal muscle phenocopied depletion of ankyrin-B and resulted in
      loss of sarcolemmal dystrophin, dystroglycan, and microtubules. Moreover,
      mutations of ankyrin-B and of dynactin-4 that selectively impaired binary
      interactions between these proteins resulted in loss of their costamere
      localizing activity and increased muscle fiber fragility as a result of loss of
      costamere-associated dystrophin and dystroglycan. In addition, costamere
      association of dynactin-4 did not require dystrophin but did depend on beta2
      spectrin and ankyrin-B, whereas costamere association of ankyrin-B required beta2
      spectrin. Together, these results are consistent with a functional hierarchy
      beginning with beta2 spectrin recruitment of ankyrin-B to costameres. Ankyrin-B
      then interacts with dynactin-4 and dystrophin, whereas dynactin-4 collaborates
      with dystrophin in coordinating costamere-aligned microtubules.

PMID- 21186324
TI  - Fusarium temperatum sp. nov. from maize, an emergent species closely related to
      Fusarium subglutinans.
AB  - A large number of Fusarium isolates closely related to F. subglutinans were
      collected from maize in Belgium. We used a robust polyphasic approach to describe
      a new biological species, Fusarium temperatum, within the Gibberella fujikuroi
      species complex. F. temperatum can be distinguished from F. subglutinans and from
      other Fusarium species within the Gibberella fujikuroi species complex with AFLP
      fingerprint profile, differences in the translation elongation factor 1-alpha and
      beta-tubulin DNA sequence and interspecies mating compatibility analyses.
      Intraspecies mating compatibility suggests that sexual reproduction might be
      common for field isolates of F. temperatum, and reliable female fertile mating
      population tester strains were proposed for this heterothallic species.

PMID- 21186325
TI  - Botryosphaeriaceae associated with Pterocarpus angolensis (kiaat) in South
      Africa.
AB  - There have been several recent reports of Pterocarpus angolensis (kiaat) trees
      dying in South Africa, Zambia and Zimbabwe, where this tree is used in
      traditional medicine and is a valuable source of timber for woodcarving and
      furniture. A survey of material from diseased P. angolensis trees in South Africa
      yielded isolates of the Botryosphaeriaceae, an important fungal family known to
      cause a number of tree diseases. The aim of this study was to identify these
      Botryosphaeriaceae and to determine their pathogenicity to P. angolensis with
      branch inoculations. Seven species of the Botryosphaeriaceae were identified
      based on a combination of morphological characteristics and sequences from the
      ITS and EF-1alpha gene regions. Four of these represent undescribed taxa for
      which the names Pseudofusicoccum violaceum, P. olivaceum, Diplodia alatafructa
      and Fusicoccum atrovirens are provided. The remaining three species collected
      include Lasiodiplodia theobromae, L. pseudotheobromae and L. crassispora.
      Inoculation trials on tree branches showed that L. pseudotheobromae and one
      isolate of D. alatafructa differed significantly from control inoculations. The
      high levels of virulence and common occurrence of L. pseudotheobromae suggest
      that this species could play a role in tree dieback and death.

PMID- 21186326
TI  - Dipteran-associated Harpellales from lowland and submontane tropical rain forests
      of Veracruz (Mexico).
AB  - We report on the species of Harpellales found in dipteran hosts during two
      surveys (32 field d) in the state of Veracruz, Mexico. One new morphospecies,
      Genistellospora dorsicaudata, is described with particular attention to the
      position of the terminal cell associated with fully developed fertile thalli
      bearing sexual spores. We emend the description of G. guanacastensis to include
      morphometrics on the zygospores, based on discovery of the sexual spores for that
      species in our collections. Thirteen other previously described species, which
      are new for Mexico, include G. homothallica, Pennella montana, Simuliomyces
      microsporus, Smittium aciculare, S. brasiliense (in a new host type), S.
      culisetae, S. dipterorum, S. microsporum, S. simulii and the unbranched species
      Harpella melusinae, H. tica, Stachylina grandispora and S. paucispora. Some
      species have been described but not named, specifically one each of Harpella,
      Pennella and Smittium. All taxa are identified morphologically, illustrated and
      additional details on their ecology are provided.

PMID- 21186327
TI  - Molecular phylogenetics of the Gloeophyllales and relative ages of clades of
      Agaricomycotina producing a brown rot.
AB  - The Gloeophyllales is a recently described order of Agaricomycotina containing a
      morphologically diverse array of polypores (Gloeophyllum), agarics (Neolentinus,
      Heliocybe) and resupinate fungi (Veluti-Veluticeps, Boreostereum,
      Chaetodermella), most of which have been demonstrated to produce a brown-rot mode
      of wood decay and are found preferentially on coniferous substrates. Multiple
      phylogenetic studies have included taxa of Gloeophyllales, but none have sampled
      the order thoroughly, and so far only ribosomal RNA genes have been used.
      Consequently the limits and higher level placement of the Gloeophyllales are
      obscure. We obtained sequence data for three protein-coding genes (rpb2, atp6,
      tef1) and three rRNA regions (nuc-ssu, nuc-lsu, 5.8S) in 19 species of
      Gloeophyllales representing seven genera and analyzed them together with a
      diverse set of Agaricomycotina, emphasizing Polyporales. Boreostereum, which is
      suspected to produce a white rot, is the sister group of the rest of the
      Gloeophyllales, all of which produce a brown rot. Gloeophyllum contains at least
      two independent clades, one of which might correspond to the genus Osmoporus.
      White rot and resupinate fruiting bodies appear to be plesiomorphic in
      Gloeophyllales. Relaxed molecular clock analyses suggest that the Gloeophyllales
      arose in the Cretaceous, after the origin of Pinaceae.

PMID- 21186328
TI  - Quantitative real-time PCR assay for rapid detection of plant and human
      pathogenic Macrophomina phaseolina from field and environmental samples.
AB  - A real-time qPCR assay was developed to detect and quantify Macrophomina
      phaseolina abundance in rhizosphere soil and plant tissue. Both TaqMan and SYBR
      green techniques were targeted on ~ 1 kb sequence characterized amplified region
      (SCAR) of M. phaseolina and two sets of specific primers were designed for SYBR
      green (MpSyK) and TaqMan (MpTqK) assays. No cross-hybridization and no
      fluorescent signal exceeding the baseline threshold was observed in TaqMan and
      SYBR green assays, respectively. The minimum detection limit or sensitivity of
      TaqMan assay was 30 fg/MUL of M. phaseolina DNA and limit of quantification of M.
      phaseolina viable population was estimated as 0.66 * 10(5) CFU/g soil(-1)
      equivalent to 10 pg/MUL of target DNA. This is the first report which
      demonstrated real-time qPCR assays with greater specificity and sensitivity to
      detect M. phaseolina population in soil and plant materials.

PMID- 21186329
TI  - Is accurate prediction of gait in nonambulatory stroke patients possible within
      72 hours poststroke? The EPOS study.
AB  - BACKGROUND: Early prognosis, adequate goal setting, and referral are important
      for stroke management. OBJECTIVE: To investigate if independent gait 6 months
      poststroke can be accurately predicted within the first 72 hours poststroke,
      based on simple clinical bedside tests. Reassessment on days 5 and 9 was used to
      check whether accuracy changed over time. METHODS: In 154 first-ever ischemic
      stroke patients unable to walk independently, 19 demographic and clinical
      variables were assessed within 72 hours and again on days 5 and 9 poststroke.
      Multivariable logistic modeling was applied to identify early prognostic factors
      for regaining independent gait, defined as >=4 points on the Functional
      Ambulation Categories. RESULTS: Multivariable modeling showed that patients with
      an independent sitting balance (Trunk Control Test-sitting; 30 seconds) and
      strength of the hemiparetic leg (Motricity Index leg; eg, visible contraction for
      all 3 items, or movement against resistance but weaker for 1 item) on day 2
      poststroke had a 98% probability of achieving independent gait at 6 months.
      Absence of these features in the first 72 hours was associated with a probability
      of 27%, declining to 10% by day 9. CONCLUSIONS: Accurate prediction of
      independent gait performance can be made soon after stroke, using 2 simple
      bedside tests: "sitting balance" and "strength of the hemiparetic leg." This
      knowledge is useful for making early clinical decisions regarding treatment goals
      and discharge planning at hospital stroke units.

PMID- 21186331
TI  - High plasma concentrations of transforming growth factor-beta and tissue
      inhibitor of metalloproteinase-1: potential non-invasive predictors for
      electroanatomical remodeling of atrium in patients with non-valvular atrial
      fibrillation.
AB  - BACKGROUND: The degree of electroanatomical remodeling of the left atrial (LA)
      affects the clinical outcome after rhythm control of atrial fibrillation (AF).
      Our hypothesis was that plasma concentrations of transforming growth factor (TGF)
      beta and tissue inhibitor of metalloproteinase (TIMP)-1 reflect LA voltage and
      structural remodeling in patients with non-valvular AF. METHODS AND RESULTS: In
      the study, 242 patients (male 79.4%, 55.1 +/- 11.0 years old) with AF (155
      paroxysmal AF, 87 persistent AF) underwent catheter ablation. Pre-ablation plasma
      concentrations of TGF-beta and TIMP-1 and the degree of electroanatomical
      remodeling quantified by LA voltage map (NavX) and 3D-CT were evaluated. The mean
      LA voltage and volume were compared in patients with high TGF-beta (>=10.0 ng/ml,
      H-TGF) vs. low TGF-beta (<10.0 ng/ml, L-TGF) and high TIMP-1 (>=1.1 ng/ml, H
      TIMP) vs. low TIMP-1 (<1.1 ng/ml, L-TIMP). Patients with H-TGF had lower mean LA
      voltage (P=0.014) and greater LA volume (P=0.022), particularly, posterior venous
      LA volume (P=0.005) than those with L-TGF. In patients with H-TIMP, the mean LA
      voltage (P=0.019) was lower than those with L-TIMP. LA volume was significantly
      higher (P<0.001) in patients with ejection fraction <=58% than those with >58%.
      CONCLUSIONS: In patients with non-valvular AF, high plasma concentrations TGF
      beta and TIMP-1 and low ejection fraction were closely related with
      electroanatomical remodeling of LA.

PMID- 21186332
TI  - Attainment of glycaemic goals by step-up therapy with biphasic insulin aspart
      70/30 in Japanese type 2 diabetic patients.
AB  - We have made step-up titration protocol with biphasic insulin aspart-70/30 (BIAsp
      30), and tried to achieve glycemic goals in poorly controlled Japanese type 2
      diabetic patients. We summarized all results obtained to analyze the
      effectiveness of our protocol. The target of glycaemic control was defined as
      HbA1c over 7.0 %. In our insulin initiation protocol, all patients started a once
      daily injection of BIAsp 30 before the breakfast in addition to their oral
      hypoglycaemic agents. The patients who could not achieve the target from 12 to 16
      weeks after the start of insulin treatment proceeded to twice daily insulin
      injection before breakfast and dinner. Next, the patients who could not achieve
      the target from 12 to 16 weeks after the addition of another BIAsp injection
      proceeded to thrice daily insulin injection before each meal a day. The results
      of 39 patients were analyzed, and 10.3 % of all patients achieved the target
      after the start of once daily injection of BIAsp 30, 41.7 % achieved in twice
      daily injection of BIAsp, and 51.4 % achieved in thrice daily injection of BIAsp.
      Daily insulin dose at the end of each treatment was 9.3+/-4.1 U in once daily,
      17.4+/-6.3 U in twice daily, and 28.4+/-10.4 U in thrice daily. Total body weight
      increase by 2.0+/-2.6 kg. The initiation and titration protocol with BIAsp 30
      improved glycaemic control, and increased the number of patients with the
      achievement of glycaemic goals.

PMID- 21186330
TI  - Abbreviated environmental enrichment enhances neurobehavioral recovery comparably
      to continuous exposure after traumatic brain injury.
AB  - BACKGROUND: Environmental enrichment (EE) is a complex living milieu that has
      been shown to enhance functional recovery versus standard (STD) housing after
      experimental traumatic brain injury (TBI) and therefore may be considered a
      rodent correlate of rehabilitation. However, the typical EE paradigm consists of
      continuous exposure to enrichment after TBI, which is inconsistent with the
      limited time frame in clinical rehabilitation. OBJECTIVE: To determine whether
      abbreviated EE (ie, rehabilitation-relevant dose response) confers benefits
      similar to typical EE after TBI. METHODS: Adult male rats received either a
      controlled cortical impact (2.8 mm depth at 4 m/s) or sham injury and were then
      randomly assigned to TBI + EE, TBI + EE (2 hours), TBI + EE (4 hours), TBI + EE
      (6 hours), TBI + STD, and respective sham controls. Motor (beam balance/beam
      walk) and cognitive (Morris water maze) performance was assessed on postoperative
      days 1 to 5 and 14 to 19, respectively. RESULTS: The TBI + EE (2 hours) and TBI +
      EE (4 hours) groups were not statistically different from the TBI + STD group in
      any behavioral assessment. In contrast, the TBI + EE (6 hours) group exhibited
      significant enhancement of motor and cognitive performance when compared with the
      TBI + STD group, as well as the TBI + EE (2 hours) and TBI + EE (4 hours) groups
      (P < .003), and did not differ from the TBI + EE (typical) group. CONCLUSIONS:
      These data demonstrate that abbreviated EE (6 hours) produces motor and cognitive
      benefits similar to continuous EE after TBI and thus may be considered a dose
      relevant rehabilitation paradigm.

PMID- 21186333
TI  - Association of serum bone morphogenetic protein 4 levels with obesity and
      metabolic syndrome in non-diabetic individuals.
AB  - Bone morphogenetic protein 4 (BMP-4) is involved in the earliest stages of
      adipocyte differentiation and is recognized as an adipogenic factor for white
      adipose tissue. The association of serum BMP-4 levels with anthropometric and
      metabolic parameters has not been previously studied. We aimed to explore the
      relationship of serum BMP-4 levels with obesity and metabolic syndrome. Serum BMP
      4 levels were measured in 104 non-diabetic individuals from the Chungju Metabolic
      Disease Cohort Study. Anthropometric measurements and components of metabolic
      syndrome were assessed in all patients. Serum BMP-4 levels were significantly
      increased in individuals with obesity or metabolic syndrome. After adjusting for
      age and gender, serum BMP-4 levels were positively correlated with body mass
      index, waist circumference (WC), waist-to-hip ratio, fasting plasma insulin,
      homeostasis model assessment index, and triglycerides and were negatively
      correlated with high-density lipoprotein (HDL) cholesterol. Among these
      parameters, WC and HDL cholesterol were found to be independent contributing
      factors for serum BMP-4 levels. Serum BMP-4 levels were also significantly higher
      in subjects with positive diagnostic criteria for each component of metabolic
      syndrome. The area under the receiver operating characteristic curve for BMP-4
      was 0.661 (P = 0.022, 95% CI = 0.528 to 0.794) and the cut-off value was 2.84
      pg/mL. This is the first demonstration that serum BMP-4 levels are associated
      with adiposity, insulin resistance, and the presence of metabolic syndrome.
      Whether BMP-4 may be involved in the pathogenesis of obesity and metabolic
      syndrome deserves further investigation.

PMID- 21186335
TI  - Possible involvement of the transient receptor potential vanilloid type 1 channel
      in postoperative adhesive obstruction and its prevention by a kampo (traditional
      Japanese) medicine, daikenchuto.
AB  - This study focused on the localization of transient receptor potential vanilloid
      type 1 (TRPV1) in the intestines in postoperative adhesion model rats and
      investigated the underlying mechanism for the anti-adhesion action of daikenchuto
      (DKT), especially in relation to TRPV1. Postoperative intestinal adhesion was
      induced by sprinkling talc in the small intestine. The expression of TRPV1 mRNA
      was examined by in situ hybridization and real-time RT-PCR. The effects of DKT
      and its major ingredient, hydroxy sanshool, with or without ruthenium red, a TRP
      channel antagonist, on talc-induced intestinal adhesions were evaluated. The
      level of TRPV1 mRNA was higher in the adhesion regions of talc-treated rats than
      in normal small intestine of sham-operated rats. Localization of TRPV1 mRNA
      expression was identified in the submucosal plexus of both sham-operated and talc
      treated rats; and in talc-treated rats, it was observed also in the myenteric
      plexus and regions of adhesion. Capsaicin, DKT, and hydroxy sanshool
      significantly prevented formation of intestinal adhesions. The effects of DKT and
      hydroxy sanshool were abrogated by subcutaneous injection of ruthenium red. These
      results suggest that pharmacological modulation of TRPV1 might be a possible
      therapeutic option in postoperative intestinal adhesion, which might be relevant
      to the prevention of postoperative adhesive obstruction by DKT.

PMID- 21186336
TI  - Pathophysiological roles of aldosterone and mineralocorticoid receptor in the
      kidney.
AB  - Aldosterone, a steroid hormone, has traditionally been viewed as a key regulator
      of fluid and electrolyte homeostasis, as well as blood pressure, through the
      activation of mineralocorticoid receptor (MR). However, a number of studies
      performed in the last decade have revealed an important role of aldosterone/MR in
      the pathogenesis of renal injury. Aldosterone/MR-induced renal tissue injury is
      associated with increased renal inflammation and oxidative stress, fibrosis,
      mesangial cell proliferation, and podocyte injury, probably through genomic and
      non-genomic pathways. However, our preliminary data have indicated that acute
      administration of aldosterone or a selective MR antagonist, eplerenone, does not
      change blood pressure, heart rate, or renal blood flow. These data suggest that
      aldosterone/MR induces renal injury through mechanisms that are independent of
      acute changes in systemic and renal hemodynamics. In this review, we will briefly
      summarize the roles of aldosterone/MR in the pathogenesis of renal injury,
      focusing on the underlying mechanisms that are independent of systemic and renal
      hemodynamic changes.

PMID- 21186337
TI  - Hepatocyte nuclear factor 4 alpha is associated with mesenchymal-epithelial
      transition in developing kidneys of C57BL/6 mice.
AB  - During kidney development, the metanephric mesenchyme (MM) develops into the
      nephron through mesenchymal-epithelial transition (MET). We have previously
      reported that knock-down of the expression of hepatocyte nuclear factor 4 alpha
      (Hnf4a) gene induces failure of cellular organization in the condensed mesenchyme
      (CM) of cultured embryonic kidneys. To elucidate the details of MET during
      nephrogenesis, embryonic mouse kidneys were analyzed by electron microscopy,
      immunohistochemistry, and molecular biology. The findings showed that the
      intercellular junction, but not the basal lamina, was present in the CM.
      Additionally, immediately after Hnf4a gene expression, the expression of
      epithelial genes (Krt8, Tjp1, and Cdh1) increased, and those of mesenchymal genes
      (Acta1 and Vim) decreased, in the CM compared to the MM. To clarify the
      relationship between MET and Hnf4alpha, the fibroblast cell line with forced
      expression of Hnf4alpha protein were analyzed. In this model, it was noted that
      Hnf4alpha induced increasing epithelial and decreasing mesenchymal gene
      expression. In these, up-regulation of Pvrl1, -2, and Mllt4 genes which mediate
      the formation of apico-basal polarity, were found. These results, and those of
      previous findings, indicate that Hnf4alpha protein is associated with the
      initiation of MET in early nephrogenesis.

PMID- 21186338
TI  - Surgical results of percutaneous suction aspiration and drainage for pyogenic
      spondylitis.
AB  - Forty patients (24 male and 16 female; age 13-87 years, mean 66 years) with
      pyogenic spondylitis were treated by percutaneous suction aspiration and drainage
      between January 1997 and September 2007 at Kurume University Hospital. The
      surgical procedure and transpedicular approach were similar to those used for
      percutaneous discectomy in the treatment of intervertebral disc herniation. The
      average postoperative follow-up period was 22.6 months. Two patients had died by
      the time of the survey, and two had undergone multiple operations. The clinical
      outcomes were excellent in 12 patients, good in 17 patients, fair in 5 patients,
      and poor in 6 patients. The response rate (cases with "excellent" or "good"
      outcomes) was 72.5% (29 patients). Identification of the organism was possible in
      26 patients (65%). The most frequently identified organism was methicillin
      resistant Staphylococcus aureus (MRSA; 11 cases), followed by methicillin
      sensitive Staphylococcus aureus (MSSA; 5 cases) and Escherichia coli (3 cases).
      Percutaneous suction aspiration and drainage has been demonstrated as an
      effective means of treating early spondylitis. This procedure is minimally
      invasive and enables pathogen identification, histopathological diagnosis and
      even simultaneous treatment. This is the only means of treatment available for
      patients who cannot tolerate open surgery. This therapy also promises medico
      economic advantages by shortening treatment periods and eliminating open surgery.

PMID- 21186339
TI  - Changes in task-associated cerebral blood induced by role lettering: measurement
      by multichannel near-infrared spectroscopy.
AB  - Using optical topography (near-infrared spectroscopy: NIRS), relative changes in
      oxidized hemoglobin (oxy-Hb) were measured before and after the introduction of
      Role lettering. Tasks performed during measurements included antegrade (from the
      subject to other persons) and retrograde (from other persons to the subject)
      mental imaging and writing tasks. All subjects were junior high school students.
      Relative changes in oxy-Hb were measured before and 3, 6, and 12 months after the
      start of Role lettering. The region of interest (ROI) was determined based upon
      the motor cortex region of hand movement and upon relative oxy-Hb changes noted
      before any Role lettering. For antegrade mental tasks, oxy-Hb increased
      significantly in right-sided ROI after 3 months; this increase persisted at 1
      year. For retrograde mental tasks, oxy-Hb significantly increased bilaterally at
      3 months, an effect that also persisted at 1 year. With the antegrade writing
      task, no significant difference was observed throughout the study; with the
      retrograde writing task, oxy-Hb level decreased significantly in right lateral
      ROI after 6 months; the decrease persisted at 1 year. The number of words
      produced after Role lettering increased significantly in both antegrade and
      retrograde writing tasks at 1 year, compared with the number before Role
      lettering. Role lettering thus altered mental activity, particularly in the right
      hemisphere. Retrograde writing tasks, similar to those employed in the actual
      practice of Role lettering, reduced right hemispheric function; continuation of
      the task enhanced performance. Role lettering studies using NIRS may provide
      useful psychophysiologic indices.

PMID- 21186340
TI  - Association between the transition from unemployment to re-employment after
      abrupt bankruptcy and the depressive symptoms.
AB  - The study aimed to examine the effects of long-term unemployment and the
      transition from unemployment to re-employment after abrupt bankruptcy on the
      mental health of unemployed Japanese. The cases of 96 men and 54 women who were
      laid off by a large shoemaking company because of sudden bankruptcy in 1998, were
      examined for one year. The mental health of these individuals was evaluated using
      a 'self-rating questionnaire for depression (SRQ-D)'. The respondents were
      categorized by employment transition status into four groups: (1) still employed
      full-time, (2) unemployment to full-time employment, (3) unemployment to part
      time employment, and (4) still unemployed. The prevalence rate of depressive
      symptoms in the 'still unemployed' group was significantly higher (adjusted odds
      ratio (OR) = 4.33) than in the still employed group. Moreover, high levels of
      depressive symptoms were observed in the individuals in the 'unemployment to part
      time employment' group (adjusted OR = 4.93). There was no significant risk of
      depressive tendency among individuals in the 'unemployment to full-time
      employment' group. The results suggest that the negative effect of re-employment
      to part-time employment on depressive symptoms is similar to that in long-term
      unemployment.

PMID- 21186341
TI  - Factors for drop-out psychiatric treatment in patients with substance-related
      disorders.
AB  - We studied 199 inpatients and outpatients at a public psychiatric hospital to
      clarify the factors related to outcome following psychiatric care for substance
      related disorder (SRD), and we discuss approaches for more effective community
      care in the future. The percentage of patients who discontinued treatment was
      33.7%, suggesting that creation of a follow-up system for continuing outpatient
      care is an urgent task. Women were 35% more likely higher to discontinue
      treatment than men. Those with solvent dependence were 12% and 7.32 times more
      likely, respectively, to discontinue treatment than those with alcohol
      dependence. Those without complications were 2.24 times more likely than those
      with complications to discontinue treatment. Divorced patients were 18% and 6.35
      times more likely, respectively, to discontinue treatment than married patients.
      There is insufficient support for patients with solvent dependence, and we
      observed that patients tended to have little motivation to stop using drugs or
      alcohol until physical complications occurred. Among the many divorced patients,
      desire for treatment was weak following breakdown of the family. The present
      findings suggest the importance of comprehensive efforts to treat substance use
      disorder at specialist medical institutions.

PMID- 21186342
TI  - The Interaction between female sex hormone receptors and osteopontin in a rat
      hyperoxaluric model.
AB  - It is well known that the incidence of urinary stones is higher in men than
      women. Although it is believed that the lower incidence of urinary stones in
      women is due to a protective effect of estrogen, the mechanisms remain unclear.
      To clarify the relation between female sex hormones and stone matrix protein, we
      examined the interaction of estrogen receptor-alpha (ERalpha), estrogen receptor
      related receptor-alpha (ERRalpha), and stone matrix protein osteopontin (OPN) in
      a rat hyperoxaluric model and in primary cultured rat kidney cells. Adult female
      Wistar rats were divided into 6 groups. Groups 1 and 4 consisted of normal
      females, Groups 2 and 5 consisted of ovariectomized females, and Groups 3 and 6
      consisted of ovariectomized females receiving female sex hormone supplements.
      Groups 1-3 were administered distilled water, while groups 4-6 were administered
      0.5% ethyleneglycol (EG). Moreover, rat kidney primary cultured cells were
      examined after treatment with female sex hormones under various conditions. The
      expressions of ERalpha, ERRalpha and OPN-mRNA in whole kidney and primary
      cultured cells were examined using Real-Time PCR. The expressions of OPN and
      ERRalpha-mRNA were suppressed by ovariectomy. Supplementation with female sex
      hormones increased the expression of OPN and ERRalpha-mRNA. In contrast, the
      expression of ERalpha-mRNA was increased by ovariectomy and suppressed by
      supplementation with female sex hormones. The results of the mRNA expression in
      primary cultured cells matched those in the hyperoxaluric model rats. Although
      the reason for the difference in expression between ERalpha and ERRalpha-mRNA is
      unclear, estrogen may regulates OPN expression through ERalpha and/or ERRalpha,
      either independently or in combination. Moreover, the decrease of OPN induced by
      removal of estrogen may increase urinary stones in postmenopausal women.

PMID- 21186343
TI  - Anesthetic management of a patient with deteriorated cardiac function following
      cardiopulmonary resuscitation.
AB  - A 73-year-old woman suffering from an abdominal aortic aneurysm (AAA), unstable
      angina, and low cardiac function (32% of ejection fraction) was scheduled for
      abdominal aortic replacement and coronary artery bypass grafting. However, before
      the scheduled operation the patient fell into cardiopulmonary arrest with
      ventricular fibrillation due to rupture of the AAA. Immediate cardiopulmonary
      resuscitation (CPR) using epinephrine and electrical defibrillation restored the
      spontaneous circulation. Following CPR, a continuous high-dose dopamine infusion
      (15 ug/kg/min) was initiated and emergent abdominal aortic replacement was
      performed. On arrival at the operating room, the patient showed serious
      hypotension, atrial fibrillation with multifocal ventricular premature
      contractions, and metabolic acidosis. Transesophageal echocardiography (TEE)
      suggested that the circulatory collapse might have resulted from diastolic
      dysfunction and deteriorated compliance of the left ventricular (LV) wall,
      possibly due to myocardial stunning induced by myocardial ischemia, and
      tachycardia induced by hypovolemia, both of which are influenced by high doses of
      catecholamine. We accordingly transfused adequate amounts of blood products and
      gradually decreased the infusion rate of dopamine to 4 ug/kg/min, while carefully
      monitoring blood pressure, central venous pressure, and TEE. By the end of
      surgery hemodynamic parameters had recovered to near normal levels. In post
      resuscitated and hypovolemic patients, caution should be taken when administering
      high levels of exogenous catecholamines, which can induce myocardial stunning and
      circulatory collapse.

PMID- 21186344
TI  - A case of acute disseminated encephalomyelitis mimicking leukodystrophy.
AB  - Acute disseminated encephalomyelitis (ADEM) is a monophasic, immune-mediated
      demyelinating disorder that can follow immunizations or more often infections
      including rubeola, rubella, varicella, herpes zoster, mumps, Mycoplasma
      pneumoniae, or, more commonly, other nonspecific upper respiratory tract
      infections. Documentation of a preceding illness is not required to make this
      diagnosis. This report examines the case of a 9-month-old male patient presenting
      with the features of an acute leukodystrophy following innoculation with the
      mixed vaccine Pentaxim (Sanofi Pasteur, Lyon- France) while suffering from a
      lower respiratory tract infection, and who was eventually diagnosed as ADEM. The
      case is presented as a reminder that ADEM can sometimes be linked to lower
      respiratory tract infection and vaccination, and that the features in such cases
      can be confused with leukodystrophy.

PMID- 21186345
TI  - Aberrant expression of CD30 in neoplastic mast cells in high-grade mastocytosis.
AB  - Systemic mastocytosis either presents as aggressive neoplasm with short survival
      time or indolent systemic mastocytosis with normal life expectancy. In both
      instances, neoplastic mast cells usually harbor the D816V-mutated variant of KIT.
      Phenotypically, mast cells in systemic mastocytosis usually express CD25.
      However, no robust marker that discriminates between aggressive and indolent
      variants of systemic mastocytosis has been identified yet. We here report that
      CD30, also known as Ki-1 antigen, is expressed in neoplastic mast cells in a
      majority of patients with advanced systemic mastocytosis (11/13, 85%), whereas in
      most patients with indolent systemic mastocytosis (12/45, 27%; P<0.001), only a
      few if any mast cells stained positive for CD30. These results could be confirmed
      by TissueFAXS analysis in subsets of patients with indolent systemic mastocytosis
      (n=7) and advanced systemic mastocytosis (n=4; P=0.008). The mast cell leukemia
      cell line HMC-1, derived from a patient with aggressive systemic mastocytosis
      also expressed the CD30 protein. In addition, we were able to detect CD30 mRNA in
      HMC-1 cells as well as in bone marrow biopsy samples in patients with systemic
      mastocytosis. In contrast, CD30 transcripts could not be detected in bone marrow
      biopsies in cases of reactive mast cell hyperplasia and in various other myeloid
      neoplasms. In conclusion, CD30 is preferentially expressed in neoplastic mast
      cells in advanced mast cell neoplasms. Upregulated expression of CD30 in advanced
      systemic mastocytosis may thus be employed as a potential marker for grading
      systemic mastocytosis in hematopathology.

PMID- 21186346
TI  - Nox2 redox signaling maintains essential cell populations in the brain.
AB  - Reactive oxygen species (ROS) are conventionally classified as toxic consequences
      of aerobic life, and the brain is particularly susceptible to ROS-induced
      oxidative stress and damage owing to its high energy and oxygen demands. NADPH
      oxidases (Nox) are a widespread source of brain ROS implicated in seizures,
      stroke and neurodegeneration. A physiological role for ROS generation in normal
      brain function has not been established, despite the fact that mice and humans
      lacking functional Nox proteins have cognitive deficits. Using molecular imaging
      with Peroxyfluor-6 (PF6), a new selective fluorescent indicator for hydrogen
      peroxide (H(2)O(2)), we show that adult hippocampal stem/progenitor cells (AHPs)
      generate H(2)O(2) through Nox2 to regulate intracellular growth signaling
      pathways, which in turn maintains their normal proliferation in vitro and in
      vivo. Our results challenge the traditional view that brain ROS are solely
      deleterious by demonstrating that controlled ROS chemistry is needed for
      maintaining specific cell populations.

PMID- 21186347
TI  - A mammalian functional-genetic approach to characterizing cancer therapeutics.
AB  - Identifying mechanisms of drug action remains a fundamental impediment to the
      development and effective use of chemotherapeutics. Here we describe an RNA
      interference (RNAi)-based strategy to characterize small-molecule function in
      mammalian cells. By examining the response of cells expressing short hairpin RNAs
      (shRNAs) to a diverse selection of chemotherapeutics, we could generate a
      functional shRNA signature that was able to accurately group drugs into
      established biochemical modes of action. This, in turn, provided a diversely
      sampled reference set for high-resolution prediction of mechanisms of action for
      poorly characterized small molecules. We could further reduce the predictive
      shRNA target set to as few as eight genes and, by using a newly derived
      probability-based nearest-neighbors approach, could extend the predictive power
      of this shRNA set to characterize additional drug categories. Thus, a focused
      shRNA phenotypic signature can provide a highly sensitive and tractable approach
      for characterizing new anticancer drugs.

PMID- 21186348
TI  - Laboratory evolution of glutathione biosynthesis reveals natural compensatory
      pathways.
AB  - The first and highly conserved step in glutathione (GSH) biosynthesis is
      formation of gamma-glutamyl cysteine by the enzyme glutamate-cysteine ligase
      (GshA). However, bioinformatic analysis revealed that many prokaryotic species
      that encode GSH-dependent proteins lack the gene for this enzyme. To understand
      how bacteria cope without gshA, we isolated Escherichia coli DeltagshA multigenic
      suppressors that accumulated physiological levels of GSH. Mutations in both proB
      and proA, the first two genes in L-proline biosynthesis, provided a new pathway
      for gamma-glutamyl cysteine formation via the selective interception of ProB
      bound gamma-glutamyl phosphate by amino acid thiols, likely through an S-to-N
      acyl shift mechanism. Bioinformatic analysis suggested that the L-proline
      biosynthetic pathway may have a second role in gamma-glutamyl cysteine formation
      in prokaryotes. Also, we showed that this mechanism could be exploited to
      generate cytoplasmic redox buffers bioorthogonal to GSH.

PMID- 21186349
TI  - Biomimetic divalent ligands for the acute disruption of synaptic AMPAR
      stabilization.
AB  - The interactions of the AMPA receptor (AMPAR) auxiliary subunit Stargazin with
      PDZ domain-containing scaffold proteins such as PSD-95 are critical for the
      synaptic stabilization of AMPARs. To investigate these interactions, we have
      developed biomimetic competing ligands that are assembled from two Stargazin
      derived PSD-95/DLG/ZO-1 (PDZ) domain-binding motifs using 'click' chemistry.
      Characterization of the ligands in vitro and in a cellular FRET-based model
      revealed an enhanced affinity for the multiple PDZ domains of PSD-95 compared to
      monovalent peptides. In cultured neurons, the divalent ligands competed with
      transmembrane AMPAR regulatory protein (TARP) for the intracellular membrane
      associated guanylate kinase resulting in increased lateral diffusion and
      endocytosis of surface AMPARs, while showing strong inhibition of synaptic AMPAR
      currents. This provides evidence for a model in which the TARP-containing AMPARs
      are stabilized at the synapse by engaging in multivalent interactions. In light
      of the prevalence of PDZ domain clusters, these new biomimetic chemical tools
      could find broad application for acutely perturbing multivalent complexes.

PMID- 21186350
TI  - Common variants near ATM are associated with glycemic response to metformin in
      type 2 diabetes.
AB  - Metformin is the most commonly used pharmacological therapy for type 2 diabetes.
      We report a genome-wide association study for glycemic response to metformin in
      1,024 Scottish individuals with type 2 diabetes with replication in two cohorts
      including 1,783 Scottish individuals and 1,113 individuals from the UK
      Prospective Diabetes Study. In a combined meta-analysis, we identified a SNP,
      rs11212617, associated with treatment success (n = 3,920, P = 2.9 * 10(-9), odds
      ratio = 1.35, 95% CI 1.22-1.49) at a locus containing ATM, the ataxia
      telangiectasia mutated gene. In a rat hepatoma cell line, inhibition of ATM with
      KU-55933 attenuated the phosphorylation and activation of AMP-activated protein
      kinase in response to metformin. We conclude that ATM, a gene known to be
      involved in DNA repair and cell cycle control, plays a role in the effect of
      metformin upstream of AMP-activated protein kinase, and variation in this gene
      alters glycemic response to metformin.

PMID- 21186351
TI  - The genome of Theobroma cacao.
AB  - We sequenced and assembled the draft genome of Theobroma cacao, an economically
      important tropical-fruit tree crop that is the source of chocolate. This assembly
      corresponds to 76% of the estimated genome size and contains almost all
      previously described genes, with 82% of these genes anchored on the 10 T. cacao
      chromosomes. Analysis of this sequence information highlighted specific expansion
      of some gene families during evolution, for example, flavonoid-related genes. It
      also provides a major source of candidate genes for T. cacao improvement. Based
      on the inferred paleohistory of the T. cacao genome, we propose an evolutionary
      scenario whereby the ten T. cacao chromosomes were shaped from an ancestor
      through eleven chromosome fusions.

PMID- 21186352
TI  - Drosophila Piwi functions in Hsp90-mediated suppression of phenotypic variation.
AB  - Canalization, also known as developmental robustness, describes an organism's
      ability to produce the same phenotype despite genotypic variations and
      environmental influences. In Drosophila, Hsp90, the trithorax-group proteins and
      transposon silencing have been previously implicated in canalization. Despite
      this, the molecular mechanism underlying canalization remains elusive. Here using
      a Drosophila eye-outgrowth assay sensitized by the dominant Kr(irregular facets
      1)(Kr(If-1)) allele, we show that the Piwi-interacting RNA (piRNA) pathway, but
      not the short interfering RNA or micro RNA pathway, is involved in canalization.
      Furthermore, we isolated a protein complex composed of Hsp90, Piwi and Hop, the
      Hsp70/Hsp90 organizing protein homolog, and we demonstrated the function of this
      complex in canalization. Our data indicate that Hsp90 and Hop regulate the piRNA
      pathway through Piwi to mediate canalization. Moreover, they point to epigenetic
      silencing of the expression of existing genetic variants and the suppression of
      transposon-induced new genetic variation as two major mechanisms underlying piRNA
      pathway-mediated canalization.

PMID- 21186353
TI  - The genome of woodland strawberry (Fragaria vesca).
AB  - The woodland strawberry, Fragaria vesca (2n = 2x = 14), is a versatile
      experimental plant system. This diminutive herbaceous perennial has a small
      genome (240 Mb), is amenable to genetic transformation and shares substantial
      sequence identity with the cultivated strawberry (Fragaria * ananassa) and other
      economically important rosaceous plants. Here we report the draft F. vesca
      genome, which was sequenced to *39 coverage using second-generation technology,
      assembled de novo and then anchored to the genetic linkage map into seven
      pseudochromosomes. This diploid strawberry sequence lacks the large genome
      duplications seen in other rosids. Gene prediction modeling identified 34,809
      genes, with most being supported by transcriptome mapping. Genes critical to
      valuable horticultural traits including flavor, nutritional value and flowering
      time were identified. Macrosyntenic relationships between Fragaria and Prunus
      predict a hypothetical ancestral Rosaceae genome that had nine chromosomes. New
      phylogenetic analysis of 154 protein-coding genes suggests that assignment of
      Populus to Malvidae, rather than Fabidae, is warranted.

PMID- 21186354
TI  - Non-genetic heterogeneity from stochastic partitioning at cell division.
AB  - Gene expression involves inherently probabilistic steps that create fluctuations
      in protein abundances. The results from many in-depth analyses and genome-scale
      surveys have suggested how such fluctuations arise and spread, often in ways
      consistent with stochastic models of transcription and translation. But
      fluctuations also arise during cell division when molecules are partitioned
      stochastically between the two daughters. Here we mathematically demonstrate how
      stochastic partitioning contributes to the non-genetic heterogeneity. Our results
      show that partitioning errors are hard to correct, and that the resulting noise
      profiles are remarkably difficult to separate from gene expression noise. By
      applying these results to common experimental strategies and distinguishing
      between creation versus transmission of noise, we hypothesize that much of the
      cell-to-cell heterogeneity that has been attributed to various aspects of gene
      expression instead comes from random segregation at cell division. We propose
      experiments to separate between these two types of fluctuations and discuss
      future directions.

PMID- 21186355
TI  - The Cavbeta subunit prevents RFP2-mediated ubiquitination and proteasomal
      degradation of L-type channels.
AB  - It is well established that the auxiliary Cavbeta subunit regulates calcium
      channel density in the plasma membrane, but the cellular mechanism by which this
      occurs has remained unclear. We found that the Cavbeta subunit increased membrane
      expression of Cav1.2 channels by preventing the entry of the channels into the
      endoplasmic reticulum-associated protein degradation (ERAD) complex. Without
      Cavbeta, Cav1.2 channels underwent robust ubiquitination by the RFP2 ubiquitin
      ligase and interacted with the ERAD complex proteins derlin-1 and p97,
      culminating in targeting of the channels to the proteasome for degradation. On
      treatment with the proteasomal inhibitor MG132, Cavbeta-free channels were
      rescued from degradation and trafficked to the plasma membrane. The coexpression
      of Cavbeta interfered with ubiquitination and targeting of the channel to the
      ERAD complex, thereby facilitating export from the endoplasmic reticulum and
      promoting expression on the cell surface. Thus, Cavbetabeta regulates the
      ubiquitination and stability of the calcium channel complex.

PMID- 21186356
TI  - APC(Cdh1) mediates EphA4-dependent downregulation of AMPA receptors in
      homeostatic plasticity.
AB  - Homeostatic plasticity is crucial for maintaining neuronal output by
      counteracting unrestrained changes in synaptic strength. Chronic elevation of
      synaptic activity by bicuculline reduces the amplitude of miniature excitatory
      postsynaptic currents (mEPSCs), but the underlying mechanisms of this effect
      remain unclear. We found that activation of EphA4 resulted in a decrease in
      synaptic and surface GluR1 and attenuated mEPSC amplitude through a degradation
      pathway that requires the ubiquitin proteasome system (UPS). Elevated synaptic
      activity resulted in increased tyrosine phosphorylation of EphA4, which
      associated with the ubiquitin ligase anaphase-promoting complex (APC) and its
      activator Cdh1 in neurons in a ligand-dependent manner. APC(Cdh1) interacted with
      and targeted GluR1 for proteasomal degradation in vitro, whereas depletion of
      Cdh1 in neurons abolished the EphA4-dependent downregulation of GluR1. Knockdown
      of EphA4 or Cdh1 prevented the reduction in mEPSC amplitude in neurons that was a
      result of chronic elevated activity. Our results define a mechanism by which
      EphA4 regulates homeostatic plasticity through an APC(Cdh1)-dependent degradation
      pathway.

PMID- 21186357
TI  - UNC-6 and UNC-40 promote dendritic growth through PAR-4 in Caenorhabditis elegans
      neurons.
AB  - Axons navigating through the developing nervous system are instructed by external
      attractive and repulsive cues. Emerging evidence suggests the same cues control
      dendrite development, but it is not understood how they differentially instruct
      axons and dendrites. We studied a C. elegans motor neuron whose axon and dendrite
      adopt different trajectories and lengths. We found that the guidance cue UNC-6
      (Netrin) is required for both axon and dendrite development. Its repulsive
      receptor UNC-5 repelled the axon from the ventral cell body, whereas the
      attractive receptor UNC-40 (DCC) was dendritically enriched and promotes antero
      posterior dendritic growth. Although the endogenous ventrally secreted UNC-6
      instructs axon guidance, dorsal or even membrane-tethered UNC-6 could support
      dendrite development. Unexpectedly, the serine-threonine kinase PAR-4 (LKB1) was
      selectively required for the activity of the UNC-40 pathway in dendrite
      outgrowth. These data suggest that axon and dendrite of one neuron interpret
      common environmental cues with different receptors and downstream signaling
      pathways.

PMID- 21186358
TI  - Amygdala volume and social network size in humans.
AB  - We found that amygdala volume correlates with the size and complexity of social
      networks in adult humans. An exploratory analysis of subcortical structures did
      not find strong evidence for similar relationships with any other structure, but
      there were associations between social network variables and cortical thickness
      in three cortical areas, two of them with amygdala connectivity. These findings
      indicate that the amygdala is important in social behavior.

PMID- 21186360
TI  - Predictive remapping of attention across eye movements.
AB  - Many cells in retinotopic brain areas increase their activity when saccades
      (rapid eye movements) are about to bring stimuli into their receptive fields.
      Although previous work has attempted to look at the functional correlates of such
      predictive remapping, no study has explicitly tested for better attentional
      performance at the future retinal locations of attended targets. We found that,
      briefly before the eyes start moving, attention drawn to the targets of upcoming
      saccades also shifted to those retinal locations that the targets would cover
      once the eyes had moved, facilitating future movements. This suggests that
      presaccadic visual attention shifts serve to both improve presaccadic perceptual
      processing at the target locations and speed subsequent eye movements to their
      new postsaccadic locations. Predictive remapping of attention provides a sparse,
      efficient mechanism for keeping track of relevant parts of the scene when
      frequent rapid eye movements provoke retinal smear and temporal masking.

PMID- 21186359
TI  - Autoregulatory and paracrine control of synaptic and behavioral plasticity by
      octopaminergic signaling.
AB  - Adrenergic signaling has important roles in synaptic plasticity and
      metaplasticity. However, the underlying mechanisms of these functions remain
      poorly understood. We investigated the role of octopamine, the invertebrate
      counterpart of adrenaline and noradrenaline, in synaptic and behavioral
      plasticity in Drosophila. We found that an increase in locomotor speed induced by
      food deprivation was accompanied by an activity- and octopamine-dependent
      extension of octopaminergic arbors and that the formation and maintenance of
      these arbors required electrical activity. Growth of octopaminergic arbors was
      controlled by a cAMP- and CREB-dependent positive-feedback mechanism that
      required Octbeta2R octopamine autoreceptors. Notably, this autoregulation was
      necessary for the locomotor response. In addition, octopamine neurons regulated
      the expansion of excitatory glutamatergic neuromuscular arbors through Octbeta2Rs
      on glutamatergic motor neurons. Our results provide a mechanism for global
      regulation of excitatory synapses, presumably to maintain synaptic and behavioral
      plasticity in a dynamic range.

PMID- 21186361
TI  - A microfluidic array for large-scale ordering and orientation of embryos.
AB  - Quantitative studies of embryogenesis require the ability to monitor pattern
      formation and morphogenesis in large numbers of embryos, at multiple time points
      and in diverse genetic backgrounds. We describe a simple approach that greatly
      facilitates these tasks for Drosophila melanogaster embryos, one of the most
      advanced models of developmental genetics. Based on passive hydrodynamics, we
      developed a microfluidic embryo-trap array that can be used to rapidly order and
      vertically orient hundreds of embryos. We describe the physical principles of the
      design and used this platform to quantitatively analyze multiple morphogen
      gradients in the dorsoventral patterning system. Our approach can also be used
      for live imaging and, with slight modifications, could be adapted for studies of
      pattern formation and morphogenesis in other model organisms.

PMID- 21186362
TI  - Efficient modeling, simulation and coarse-graining of biological complexity with
      NFsim.
AB  - Managing the overwhelming numbers of molecular states and interactions is a
      fundamental obstacle to building predictive models of biological systems. Here we
      introduce the Network-Free Stochastic Simulator (NFsim), a general-purpose
      modeling platform that overcomes the combinatorial nature of molecular
      interactions. Unlike standard simulators that represent molecular species as
      variables in equations, NFsim uses a biologically intuitive representation:
      objects with binding and modification sites acted on by reaction rules. During
      simulations, rules operate directly on molecular objects to produce exact
      stochastic results with performance that scales independently of the reaction
      network size. Reaction rates can be defined as arbitrary functions of molecular
      states to provide powerful coarse-graining capabilities, for example to merge
      Boolean and kinetic representations of biological networks. NFsim enables
      researchers to simulate many biological systems that were previously inaccessible
      to general-purpose software, as we illustrate with models of immune system
      signaling, microbial signaling, cytoskeletal assembly and oscillating gene
      expression.

PMID- 21186363
TI  - On the structural basis of modal gating behavior in K(+) channels.
AB  - Modal-gating shifts represent an effective regulatory mechanism by which ion
      channels control the extent and time course of ionic fluxes. Under steady-state
      conditions, the K(+) channel KcsA shows three distinct gating modes, high-P(o),
      low-P(o) and a high-frequency flicker mode, each with about an order of magnitude
      difference in their mean open times. Here we show that in the absence of C-type
      inactivation, mutations at the pore-helix position Glu71 unmask a series of
      kinetically distinct modes of gating in a side chain-specific way. These gating
      modes mirror those seen in wild-type channels and suggest that specific
      interactions in the side chain network surrounding the selectivity filter, in
      concert with ion occupancy, alter the relative stability of pre-existing
      conformational states of the pore. The present results highlight the key role of
      the selectivity filter in regulating modal gating behavior in K(+) channels.

PMID- 21186364
TI  - Substrate binding on the APC/C occurs between the coactivator Cdh1 and the
      processivity factor Doc1.
AB  - The anaphase-promoting complex/cyclosome (APC/C) is a 22S ubiquitin ligase
      complex that initiates chromosome segregation and mitotic exit. We have used
      biochemical and electron microscopic analyses of Saccharomyces cerevisiae and
      human APC/C to address how the APC/C subunit Doc1 contributes to recruitment and
      processive ubiquitylation of APC/C substrates, and to understand how APC/C
      monomers interact to form a 36S dimeric form. We show that Doc1 interacts with
      Cdc27, Cdc16 and Apc1 and is located in the vicinity of the cullin-RING module
      Apc2-Apc11 in the inner cavity of the APC/C. Substrate proteins also bind in the
      inner cavity, in close proximity to Doc1 and the coactivator Cdh1, and induce
      conformational changes in Apc2-Apc11. Our results suggest that substrates are
      recruited to the APC/C by binding to a bipartite substrate receptor composed of a
      coactivator protein and Doc1.

PMID- 21186365
TI  - Selective silencing of mutated mRNAs in DM1 by using modified hU7-snRNAs.
AB  - We describe a function for modified human U7 small nuclear RNAs (hU7-snRNAs)
      distinct from modification of pre-mRNA splicing events. Engineered hU7-snRNAs
      containing a poly-CAG antisense sequence targeting the expanded CUG repeats of
      mutant DMPK transcripts in myotonic dystrophy caused specific degradation of
      pathogenic DMPK mRNAs without affecting the products of wild-type DMPK alleles.
      Abolition of the RNA gain-of-function toxicity that is responsible for
      pathogenesis supports the use of hU7-snRNAs for gene silencing in RNA-dominant
      disorders in which expanded repeats are expressed.

PMID- 21186366
TI  - Nuclear adaptor Ldb1 regulates a transcriptional program essential for the
      maintenance of hematopoietic stem cells.
AB  - The nuclear adaptor Ldb1 functions as a core component of multiprotein
      transcription complexes that regulate differentiation in diverse cell types. In
      the hematopoietic lineage, Ldb1 forms a complex with the non-DNA-binding adaptor
      Lmo2 and the transcription factors E2A, Scl and GATA-1 (or GATA-2). Here we
      demonstrate a critical and continuous requirement for Ldb1 in the maintenance of
      both fetal and adult mouse hematopoietic stem cells (HSCs). Deletion of Ldb1 in
      hematopoietic progenitors resulted in the downregulation of many transcripts
      required for HSC maintenance. Genome-wide profiling by chromatin
      immunoprecipitation followed by sequencing (ChIP-Seq) identified Ldb1 complex
      binding sites at highly conserved regions in the promoters of genes involved in
      HSC maintenance. Our results identify a central role for Ldb1 in regulating the
      transcriptional program responsible for the maintenance of HSCs.

PMID- 21186367
TI  - The splicing regulator PTBP2 interacts with the cytidine deaminase AID and
      promotes binding of AID to switch-region DNA.
AB  - During immunoglobulin class-switch recombination (CSR), the cytidine deaminase
      AID induces double-strand breaks into transcribed, repetitive DNA elements called
      switch sequences. The mechanism that promotes the binding of AID specifically to
      switch regions remains to be elucidated. Here we used a proteomic screen with in
      vivo biotinylation of AID to identify the splicing regulator PTBP2 as a protein
      that interacts with AID. Knockdown of PTBP2 mediated by short hairpin RNA in B
      cells led to a decrease in binding of AID to transcribed switch regions, which
      resulted in considerable impairment of CSR. PTBP2 is thus an effector of CSR that
      promotes the binding of AID to switch-region DNA.

PMID- 21186368
TI  - miR-499 regulates mitochondrial dynamics by targeting calcineurin and dynamin
      related protein-1.
AB  - Myocardial infarction is a leading cause of mortality worldwide. Here we report
      that modulation of microRNA-499 (miR-499) levels affects apoptosis and the
      severity of myocardial infarction and cardiac dysfunction induced by ischemia
      reperfusion. We found that both the alpha- and beta-isoforms of the calcineurin
      catalytic subunit are direct targets of miR-499 and that miR-499 inhibits
      cardiomyocyte apoptosis through its suppression of calcineurin-mediated
      dephosphorylation of dynamin-related protein-1 (Drp1), thereby decreasing Drp1
      accumulation in mitochondria and Drp1-mediated activation of the mitochondrial
      fission program. We also found that p53 transcriptionally downregulates miR-499
      expression. Our data reveal a role for miR-499 in regulating the mitochondrial
      fission machinery and we suggest that modulation of miR-499 levels may provide a
      therapeutic approach for treating myocardial infarction.

PMID- 21186370
TI  - Meiotic crossover: what controls the breaks?

PMID- 21186371
TI  - The effects of acquired paternal obesity on the next generation.

PMID- 21186372
TI  - Role of connexins in microvascular dysfunction during inflammation.
AB  - In arterioles, a locally initiated diameter change can propagate rapidly along
      the vessel length (arteriolar conducted response), thus contributing to
      arteriolar hemodynamic resistance. The response is underpinned by electrical
      coupling along the arteriolar endothelial layer. Connexins (Cx; constituents of
      gap junctions) are required for this coupling. This review addresses the effect
      of acute systemic inflammation (sepsis) on arteriolar conduction and
      interendothelial electrical coupling. Lipopolysaccharide (LPS; an initiating
      factor in sepsis) and polymicrobial sepsis (24 h model) attenuate conducted
      vasoconstriction in mice. In cultured microvascular endothelial cells harvested
      from rat and mouse skeletal muscle, LPS reduces both conducted hyperpolarization
      depolarization along capillary-like structures and electrical coupling along
      confluent cell monolayers. LPS also tyrosine-phosphorylates Cx43 and serine
      dephosphorylates Cx40. Since LPS-reduced coupling is Cx40- but not Cx43
      dependent, only Cx40 dephosphorylation may be consequential. Nitric oxide (NO)
      overproduction is critical in advanced sepsis, since the removal of this
      overproduction prevents the attenuated conduction. Consistently, (i) exogenous NO
      in cultured cells reduces coupling in a Cx37-dependent manner, and (ii) the
      septic microvasculature in vivo shows no Cx40 phenotype. A complex role emerges
      for endothelial connexins in sepsis. Initially, LPS may reduce interendothelial
      coupling and arteriolar conduction by targeting Cx40, whereas NO overproduction
      in advanced sepsis reduces coupling and conduction by targeting Cx37 instead.

PMID- 21186369
TI  - Receptor-mediated activation of ceramidase activity initiates the pleiotropic
      actions of adiponectin.
AB  - The adipocyte-derived secretory factor adiponectin promotes insulin sensitivity,
      decreases inflammation and promotes cell survival. No unifying mechanism has yet
      explained how adiponectin can exert such a variety of beneficial systemic
      effects. Here, we show that adiponectin potently stimulates a ceramidase activity
      associated with its two receptors, AdipoR1 and AdipoR2, and enhances ceramide
      catabolism and formation of its antiapoptotic metabolite--sphingosine-1-phosphate
      (S1P)--independently of AMP-dependent kinase (AMPK). Using models of inducible
      apoptosis in pancreatic beta cells and cardiomyocytes, we show that transgenic
      overproduction of adiponectin decreases caspase-8-mediated death, whereas genetic
      ablation of adiponectin enhances apoptosis in vivo through a sphingolipid
      mediated pathway. Ceramidase activity is impaired in cells lacking both
      adiponectin receptor isoforms, leading to elevated ceramide levels and enhanced
      susceptibility to palmitate-induced cell death. Combined, our observations
      suggest a unifying mechanism of action for the beneficial systemic effects
      exerted by adiponectin, with sphingolipid metabolism as its core upstream
      signaling component.

PMID- 21186373
TI  - Cree antidiabetic plant extracts display mechanism-based inactivation of CYP3A4.
AB  - Seventeen Cree antidiabetic medicinal plants were studied to determine their
      potential to inhibit cytochrome P450 3A4 (CYP3A4) through mechanism-based
      inactivation (MBI). The ethanolic extracts of the medicinal plants were studied
      for their inhibition of CYP3A4 using the substrates testosterone and
      dibenzylfluorescein (DBF) in high pressure liquid chromatography (HPLC) and
      microtiter fluorometric assays, respectively. Using testosterone as a substrate,
      extracts of Alnus incana, Sarracenia purpurea, and Lycopodium clavatum were
      identified as potent CYP3A4 MBIs, while those from Abies balsamea, Picea mariana,
      Pinus banksiana, Rhododendron tomentosum, Kalmia angustifolia, and Picea glauca
      were identified as less potent inactivators. Not unexpectedly, the other
      substrate, DBF, showed a different profile of inhibition. Only A. balsamea was
      identified as a CYP3A4 MBI using DBF. Abies balsamea displayed both NADPH- and
      time-dependence of CYP3A4 inhibition using both substrates. Overall, several of
      the medicinal plants may markedly deplete CYP3A4 through MBI and, consequently,
      decrease the metabolism of CYP3A4 substrates including numerous medications used
      by diabetics.

PMID- 21186374
TI  - Role of large-conductance Ca2+-activated K+ channels in adenosine A1 receptor
      mediated pharmacological postconditioning in H9c2 cells.
AB  - Ischaemic postconditioning is a phenomenon whereby short periods of ischaemia
      applied during the start of reperfusion protect the myocardium from the damaging
      consequences of reperfusion. As such, pharmacological-induced postconditioning
      represents an attractive therapeutic strategy for reducing reperfusion injury
      during cardiac surgery and following myocardial infarction. The primary aim of
      this study was to determine the role of large-conductance Ca2(+)-activated
      potassium channels (BK(Ca) channels) in adenosine A1 receptor-induced
      pharmacological postconditioning in the rat embryonic cardiomyoblast-derived cell
      line H9c2. H9c2 cells were exposed to 6 h hypoxia (0.5% O2) followed by 18 h
      reoxygenation (H/R) after which cell viability was assessed by monitoring lactate
      dehydrogenase (LDH) release and caspase-3 activation. The adenosine A1 receptor
      agonist N6-cyclopentyladenosine (CPA; 100 nmol/L) or the BK(Ca) channel opener
      NS1619 (10 umol/L) were added for 30 min at the start of reoxygenation following
      6 h hypoxic exposure. Where appropriate, cells were treated (15 min) before
      pharmacological postconditioning with the BK(Ca) channel blockers paxilline (1
      umol/L) or iberiotoxin (100 nmol/L). Pharmacological postconditioning with CPA or
      NS1619 significantly reduced H/R-induced LDH release. Treatment with paxilline or
      iberiotoxin attenuated adenosine A1 receptor and NS1619-induced pharmacological
      postconditioning. These results have shown for the first time that BK(Ca)
      channels are involved in adenosine A1 receptor-induced pharmacological
      postconditioning in a cell model system.

PMID- 21186375
TI  - The role of estrogen and progesterone, administered alone and in combination, in
      modulating cytokine concentration following traumatic brain injury.
AB  - Cytokines play an important role in the pathophysiology of traumatic brain injury
      (TBI). This study was designed to determine the effects of administering
      progesterone (P) and estrogen (E), alone and in combination, on brain water
      content, blood-brain barrier (BBB) disturbance, and brain level of cytokines
      following diffuse TBI. Ovariectomized rats were divided into 9 groups, treated
      with vehicle, E1, E2, P1, P2, E1+P1, E1+P2, E2+P1, and E2+P2. Levels of BBB
      disruption (5 h), cytokines, and water content (24 h) were evaluated after TBI
      induced by the Marmarou method. Physiological (E1 and P1) and pharmacological (E2
      and P2) doses of estrogen and progesterone were administered 30 min after TBI.
      Water content in the E1+P2-treated group was higher than in the E1-treated group.
      The inhibitory effect of E2 on water content was reduced by adding progesterone.
      The inhibitory effect of E1 and E2 on Evans blue content was reduced by treatment
      with E1+P1 and E2+P2, respectively. The brain level of IL-1beta was reduced in E1
      and E2, after TBI. In the E2+P2-treated group, this level was higher than in the
      E2-treated group. The brain level of TGF-beta was also elevated by the
      administration of progesterone and estrogen alone, and reduced when the hormones
      were administered in combination. In conclusion, a combined administration of
      progesterone and estrogen inhibited the decreasing effects of administration of
      progesterone and estrogen alone on water content and BBB disruption that mediated
      to change the proinflammatory cytokines.

PMID- 21186376
TI  - Coagulation activation in an experimental pneumonia model in malnourished mice.
AB  - Malnutrition induces a decrease in immunity that affects the ability of the
      organism to deal with an infectious challenge. The clotting system is considered
      a branch of immunity and its activation is important in the pathogenesis of an
      infectious disease. This work was conducted to determine coagulation
      modifications in malnourished hosts before and during infection. Weaned mice were
      malnourished via a protein-free diet. Well-nourished control mice (WNC) consumed
      a balanced conventional diet. Malnourished mice (MN) and WNC were challenged
      intranasally with Streptococcus pneumoniae. Blood, bronchoalveolar lavages (BAL),
      and lung samples were taken at different times post infection. The results were
      that MN showed altered hemostatic tests and fibrin(ogen) deposits in the lung.
      Thus, an increase in thrombin-antithrombin complexes (TATc) in plasma and BAL was
      observed. In the MN group, infection induced a rise in TATc in plasma and BAL and
      increased plasma fibrinogen and fibrin(ogen) deposits in the lung. A decrease in
      activated protein C and antithrombin in BAL and an early decrease followed by an
      increase in plasma Factor VIII were also observed. Thus, malnourishment induced a
      procoagulant state increased by infection. This is the first work that presents
      results of an exhaustive study of coagulation in malnourished hosts before and
      during an infection.

PMID- 21186377
TI  - Cytotoxic activity of nemorosone in human MCF-7 breast cancer cells.
AB  - Estrogen receptor (ER) antagonists have been widely used for breast cancer
      treatment; however, patients have increasingly shown resistance and sensitivity
      to the high toxicity of these drugs, and identification of novel targeted
      therapies is therefore required. To determine whether nemorosone, a polycyclic
      polyisoprenylated benzophenone isolated from floral resins of Clusia rosea Jacq.
      and Cuban propolis samples, exerts anticancer effects on human breast cancer
      cells, estrogen receptor positive (ERalpha+) MCF-7 and estrogen receptor negative
      (ERalpha-) MDA-MB-231 and LNCaP cells were used. Cells were treated with
      nemorosone alone or in association with 17beta-estradiol (E2) or an ER
      antagonist, ICI 182,780, a selective ER downregulator that completely abrogates
      estrogen-sensitive gene transcription. Nemorosone inhibited the cell viability of
      ERalpha+ but not of ERalpha- cells. In MCF-7, nemorosone induced inhibition of
      cell growth by blocking the cell cycle in the G0/G1 phase. Moreover, the
      expression of pERK1/2 and pAkt, considered to be hallmarks of the nongenomic
      estrogen signalling pathway, were reduced in MCF-7 cells treated with nemorosone.
      All these effects were enhanced by ICI 182,780. However, nemorosone was not able
      to interfere with E2-induced Ca2(+) release. These findings suggest that
      nemorosone may have therapeutic application in the treatment of breast cancer
      because of its activity on ERalpha.

PMID- 21186378
TI  - Chronic hypoxia-induced alterations in mitochondrial energy metabolism are not
      reversible in rat heart ventricles.
AB  - Chronic hypoxia alters mitochondrial energy metabolism. In the heart, oxidative
      capacity of both ventricles is decreased after 3 weeks of chronic hypoxia. The
      aim of this study was to evaluate the reversal of these metabolic changes upon
      normoxia recovery. Rats were exposed to a hypobaric environment for 3 weeks and
      then subjected to a normoxic environment for 3 weeks (normoxia-recovery group)
      and compared with rats maintained in a normoxic environment (control group).
      Mitochondrial energy metabolism was differentially examined in both left and
      right ventricles. Oxidative capacity (oxygen consumption and ATP synthesis) was
      measured in saponin-skinned fibers. Activities of mitochondrial respiratory chain
      complexes and antioxidant enzymes were measured on ventricle homogenates.
      Morphometric analysis of mitochondria was performed on electron micrographs. In
      normoxia-recovery rats, oxidative capacities of right ventricles were decreased
      in the presence of glutamate or palmitoyl carnitine as substrates. In contrast,
      oxidation of palmitoyl carnitine was maintained in the left ventricle. Enzyme
      activities of complexes III and IV were significantly decreased in both
      ventricles. These functional alterations were associated with a decrease in
      numerical density and an increase in size of mitochondria. Finally, in the
      normoxia-recovery group, the antioxidant enzyme activities (catalase and
      glutathione peroxidase) increased. In conclusion, alterations of mitochondrial
      energy metabolism induced by chronic hypoxia are not totally reversible. Reactive
      oxygen species could be involved and should be investigated under such
      conditions, since they may represent a therapeutic target.

PMID- 21186380
TI  - Long-term swimming exercise does not modulate the Akt-dependent endothelial
      nitric oxide synthase phosphorylation in healthy mice.
AB  - Molecular mechanisms by which exercise exerts cardiovascular benefits are poorly
      understood. Exercise-induced increase of endothelial NO synthase (eNOS)
      phosphorylation through the protein kinase Akt has been shown to be a key
      mechanism underlying the beneficial effect of exercise in coronary artery disease
      patients. We examined whether this protective pathway might also be activated in
      long-term-exercised healthy mice. C57BL/6 wild-type mice swam for 24 weeks. A
      group of sedentary animals were used as controls. Aortic levels of total protein
      kinase Akt (protein kinase B), phosphorylated Akt at ser473 (p-Akt), total eNOS,
      phosphorylated eNOS at Ser1177 (p-eNOS), and PECAM-1 (platelet endothelial cell
      adhesion molecule-1) were assessed by Western blotting. Protein expressions of
      Akt, p-Akt, eNOS, p-eNOS, and PECAM-1 were not modulated by 24 weeks of exercise.
      The Akt-dependent eNOS phosphorylation did not seem to be a primary molecular
      adaptation in response to long-term exercise in healthy mice.

PMID- 21186379
TI  - Feeding blueberry diets inhibits angiotensin II-converting enzyme (ACE) activity
      in spontaneously hypertensive stroke-prone rats.
AB  - Feeding flavonoid-rich blueberries to spontaneously hypertensive stroke-prone
      rats (SHRSP) lowers blood pressure. To determine whether this is due to
      inhibition of angiotensin-converting enzyme (ACE) activity, as seen with other
      flavanoid-rich foods, we fed blueberries to SHRSP and normotensive rats and
      analyzed ACE activity in blood and tissues. After 2 weeks on a control diet, the
      hypertensive rats showed 56% higher levels of ACE activity in blood as compared
      with the normotensive rats (p < 0.05). Feeding a 3% blueberry diet for 2 weeks
      lowered ACE activity in the SHRSP (p < 0.05) but not the normotensive rats. ACE
      activity in plasma of SHRSP was no longer elevated at weeks 4 and 6, but
      blueberry feeding inhibited ACE in SHRSP after 6 weeks. Blueberry diets had no
      effect on ACE activity in lung, testis, kidney, or aorta. Our results suggest
      that dietary blueberries may be effective in managing early stages of
      hypertension, partially due to an inhibition of soluble ACE activity.

PMID- 21186382
TI  - Exploiting the versatility and selectivity of Mo enzymes with electrochemistry.
AB  - This article covers recent advances in the electrochemical study of the
      mononuclear molybdenum enzymes. Virtually all of these enzymes catalyse a coupled
      2-electron, O-atom transfer reaction on a substrate of either organic or
      inorganic origin. There is a remarkable commonality in structure, function and
      mechanism of the mononuclear Mo enzymes despite the diversity of their
      substrates; many that are important to environmental monitoring, food quality
      control and biomedical science. Mo enzymes routinely oxidise or reduce otherwise
      inert substrates for which there exist no rapid, simple and reliable analytical
      methods for their determination and as such represent a potentially rich source
      of proteins that may be applied in electrochemical biosensors.

PMID- 21186383
TI  - Full-dimensional quantum dynamics study of vinylidene-acetylene isomerization: a
      scheme using the normal mode Hamiltonian.
AB  - Full-dimensional quantum dynamics calculations of vinylidene-acetylene
      isomerization are performed and the state-specific resonance decay lifetimes of
      vinylidene(-d(2)) are computed. The theoretical scheme is a combination of
      several methods: normal coordinates are chosen to describe the nuclear motion of
      vinylidene, with both the parity and permutation symmetry exploited; phase space
      optimization in combination with physical considerations is used to generate an
      efficient discrete variable representation; the reaction coordinate is defined by
      us according to the three most relevant normal coordinates, along which a kind of
      optimal complex absorbing potential is imposed; the preconditioned inexact
      spectral transform method combined with an efficient preconditioner is employed
      to extract the energies and lifetimes of vinylidene. The overall computation is
      efficient. The computed energy levels generally agree with experiment well, and
      several state-specific lifetimes are reported for the first time.

PMID- 21186384
TI  - Ergot alkaloids: structure diversity, biosynthetic gene clusters and functional
      proof of biosynthetic genes.
AB  - Ergot alkaloids are toxins and important pharmaceuticals which are produced
      biotechnologically on an industrial scale. They have been identified in two
      orders of fungi and three families of higher plants. The most important producers
      are fungi of the genera Claviceps, Penicillium and Aspergillus (all belonging to
      the Ascomycota). Chemically, ergot alkaloids are characterised by the presence of
      a tetracyclic ergoline ring, and can be divided into three classes according to
      their structural features, i.e. amide- or peptide-like amide derivatives of D
      lysergic acid and the clavine alkaloids. Significant progress has been achieved
      on the molecular biological and biochemical investigations of ergot alkaloid
      biosynthesis in the last decade. By gene cloning and genome mining, gene clusters
      for ergot alkaloid biosynthesis have been identified in at least 8 different
      ascomycete species. Functions of most structure genes have been assigned to
      reaction steps in the biosynthesis of ergot alkaloids by gene inactivation
      experiments or biochemical characterisation of the overproduced proteins.

PMID- 21186385
TI  - Exploring the effect of supramolecular structures of micelles and cyclodextrins
      on fluorescence emission of local anesthetics.
AB  - Benzocaine (ethyl 4-aminobenzoate, 4) and its derivatives ethyl 2-aminobenzoate,
      2, and ethyl 3-aminobenzoate, 3, were found to form association complexes with
      supramolecular structures of micelles and cyclodextrins (CDs). The fluorescence
      emission of 2, 3 or 4 dissolved in the pseudo-micellar phase or included into
      alpha-, beta-, or gamma-CD cavity increases dramatically with respect to that
      observed in only water. High percentages of organic solvents like dioxane,
      acetonitrile, DMSO in the aqueous solution lead to a similar effect. The
      stability constants of the complexes formed between these drugs and cyclodextrins
      have been determined. In neutral or acid medium, a 1:1 stoichiometry for drug:CD
      complexes have been found, whereas in alkaline medium 1:2 stoichiometry was also
      detected in some cases. Kinetic studies of both the nitrosation of the amine
      group and the alkaline hydrolysis of the ester function was employed to infer the
      conformation of the complexes as well as to evaluate their stability constants.
      Theoretical calculations to optimize the molecular structure of 2, 3 and 4 allow
      us to propose possible geometries of the complexes that are in agreement with the
      experimental data.

PMID- 21186386
TI  - A new peptide motif in the formation of supramolecular double helices.
AB  - The single crystal X-ray diffraction studies of a new tripeptide motif Boc-Tyr
      Aib-Xaa-OMe (Xaa = Leu/Ile/Ala) reveal that the peptides adopt beta-turn
      conformations which self-assemble to form a supramolecular double helical
      structure using various non-covalent interactions in the solid state and the
      peptides exhibit a type-III N(2) sorption isotherm.

PMID- 21186387
TI  - Aerosol-spraying preparation of a mesoporous hollow spherical BiFeO3 visible
      photocatalyst with enhanced activity and durability.
AB  - A facile aerosol-spraying approach was developed to prepare mesoporous BiFeO(3)
      hollow spheres with enhanced activity and durability in visible photocatalysis.

PMID- 21186388
TI  - Cobalt(II) complexes of terpyridine bases as photochemotherapeutic agents showing
      cellular uptake and photocytotoxicity in visible light.
AB  - Cobalt(II) complexes of terpyridine bases [Co(L)2](ClO4)2 (1-3), where L is 4'
      phenyl-2,2':6',2''-terpyridine (ph-tpy in 1), 4'-(9-anthracenyl)-2,2':6',2''
      terpyridine (an-tpy in 2) and 4'-(1- pyrenyl)-2,2':6',2''-terpyridine (py-tpy in
      3), are prepared and their photo-induced DNA and protein cleavage activity and
      photocytotoxic property in HeLa cells studied. The 1 : 2 electrolytic and three
      electron paramagnetic complexes show a visible band near 550 nm in DMF-Tris-HCl
      buffer. The complexes 1-3 show emission spectral bands at 355, 421 and 454 nm,
      respectively, when excited at 287, 368 and 335 nm. The quantum yield values for 1
      3 in DMF-H2O (2 : 1 v/v) are 0.025, 0.060 and 0.28, respectively. The complexes
      are redox active in DMF-0.1 M TBAP. The Co(III)-Co(II) and Co(II)-Co(I) couples
      appear as quasi-reversible cyclic voltammetric responses near 0.2 and -0.7 V vs.
      SCE, respectively. Complexes 2 and 3 are avid binders to calf thymus DNA giving
      K(b) value of ~106 M-1. The complexes show chemical nuclease activity. Complexes
      2 and 3 exhibit oxidative cleavage of pUC19 DNA in UV-A and visible light. The
      DNA photocleavage reaction of 3 at 365 nm shows formation of singlet oxygen and
      hydroxyl radical species, while only hydroxyl radical formation is evidenced in
      visible light. Complexes 2 and 3 show non-specific photo-induced bovine serum
      albumin protein cleavage activity at 365 nm. The an-tpy and py-tpy complexes
      exhibit significant photocytotoxicity in HeLa cervical cancer cells on exposure
      to visible light giving IC50 values of 24.2 and 7.6 MUM, respectively. Live cell
      imaging study shows accumulation of the complexes in the cytosol of HeLa cancer
      cells.

PMID- 21186389
TI  - Synthesis, spectroscopy and electronic structure of the vinylidene and alkynyl
      complexes [W(C=CHR)(dppe)(eta-C7H7)](+) and [W(C=CR)(dppe)(eta-C7H7](n+) (n = 0
      or 1).
AB  - The first examples of vinylidene complexes of the cycloheptatrienyl tungsten
      system [W(C=CHR)(dppe)(eta-C7H7)](+) (dppe = Ph2PCH2CH2PPh2; R = H, 3; Ph, 4;
      C6H4-4-Me, 5) have been synthesised by reaction of [WBr(dppe)(eta-C7H7)], 1, with
      terminal alkynes HC=CR; a one-pot synthesis of 1 from [WBr(CO)2(eta-C7H7)]
      facilitates its use as a precursor. The X-ray structure of 4[PF6] reveals that
      the vinylidene ligand substituents lie in the pseudo mirror plane of the
      W(dppe)(eta-C7H7) auxiliary (vertical orientation) with the phenyl group located
      syn to the cycloheptatrienyl ring. Variable temperature 1H NMR investigations on
      [W(C=CH2)(dppe)(eta-C7H7)][PF6], 3, estimate the energy barrier to rotation about
      the W=C(alpha) bond as 62.5 +/- 2 kJ mol-1; approximately 10 kJ mol-1 greater
      than for the molybdenum analogue. Deprotonation of 4 and 5 with KOBu(t) yields
      the alkynyls [W(C=CR)(dppe)(eta-C7H7)] (R = Ph, 6; C6H4-4-Me, 7) which undergo a
      reversible one-electron oxidation at a glassy carbon electrode in CH2Cl2 with
      E(1/2) values approximately 0.12 V negative of Mo analogues. The 17-electron
      radicals [6](+) and [7](+) have been investigated by spectroelectrochemical IR,
      UV-visible and EPR methods. The electronic structures of representative
      vinylidene (3) and alkynyl (6) complexes have been investigated at the B3LYP/Def2
      SVP level. In both cases, electronic structure is characterised by a frontier
      orbital with significant metal d(z2)character and this dominates the structural
      and spectroscopic properties of the system.

PMID- 21186390
TI  - Flow focussing of particles and cells based on their intrinsic properties using a
      simple diamagnetic repulsion setup.
AB  - The continuous flow focussing and manipulation of particles and cells are
      important factors in microfluidic applications for performing accurate and
      reproducible procedures downstream. Many particle focussing methods require
      complex setups or channel designs that can limit the process and its
      applications. Here, we present diamagnetic repulsion as a simple means of
      focussing objects in continuous flow, based only on their intrinsic properties
      without the requirement of any label. Diamagnetic polystyrene particles were
      suspended in a paramagnetic medium and pumped through a capillary between a pair
      of permanent magnets, whereupon the particles were repelled by each magnet into
      the central axis of the capillary, thus achieving focussing. By investigating
      this effect, we found that the focussing was greatly enhanced with (i) increased
      magnetic susceptibility of the medium, (ii) reduced flow rate of the suspension,
      (iii) increased particle size, and (iv) increased residence time in the magnetic
      field. Furthermore, we applied diamagnetic repulsion to the flow focussing of
      living, label-free HaCaT cells.

PMID- 21186391
TI  - Spring-loading the active site of cytochrome P450cam.
AB  - A hydrogen bond network has been identified that adjusts protein-substrate
      contacts in cytochrome P450(cam) (CYP101A1). Replacing the native substrate
      camphor with adamantanone or norcamphor causes perturbations in NMR-detected NH
      correlations assigned to the network, which includes portions of a beta sheet and
      an adjacent helix that is remote from the active site. A mutation in this helix
      reduces enzyme efficiency and perturbs the extent of substrate-induced spin state
      changes at the haem iron that accompany substrate binding. In turn, the magnitude
      of the spin state changes induced by alternate substrate binding parallel the NMR
      detected perturbations observed near the haem in the enzyme active site.

PMID- 21186392
TI  - Direct transition-metal-free intramolecular C-O bond formation: synthesis of
      benzoxazole derivatives.
AB  - A direct base-mediated intramolecular carbon-oxygen bond formation has been
      developed without a transition-metal catalyst. In the presence of 2.0 equiv of
      K(2)CO(3) in DMSO at 140  degrees C, the intramolecular cyclization of o
      haloanilides affords benzoxazoles in high yields. A mechanism via an initial
      formation of a benzyne intermediate followed by nucleophilic addition to form the
      C-O bond has been proposed.

PMID- 21186393
TI  - Efficient synthesis of the anticancer beta-elemene and other bioactive elemanes
      from sustainable germacrone.
AB  - Highly efficient preparations of anticancer beta-elemene and other bioactive
      elemanes were carried out using the natural product germacrone as a renewable
      starting material. The syntheses were achieved in only 3-5 steps with excellent
      overall yields (43-54%). An enantioselective approach to these molecules is also
      described.

PMID- 21186394
TI  - Trifunctional 99mTc based radiopharmaceuticals: metal-mediated conjugation of a
      peptide with a nucleus targeting intercalator.
AB  - The development of molecular imaging agents with multiple functions has become a
      major trend in radiopharmaceutical chemistry. We present herein the syntheses of
      trifunctional compounds, combining an acridine orange (AO) based intercalator
      with a GRP receptor specific bombesin like peptide (BBN). Metal-mediated
      conjugation of these two functions via the [2 + 1] approach to the third
      function, the [M(CO)(3)](+) (M = (99m)Tc, Re) moiety, yielded the final
      trifunctional molecules. The strongly fluorescent acridine orange, a nuclear
      targeting agent, has been derivatised with 4-imidazolecarboxylate as a bidentate
      ligand and bombesin with an isonitrile group as a monodentate ligand. For cell
      and nuclear uptake studies, [Re(L(1)-BBN)(L(2)-Ical)(CO)(3)] type complexes were
      synthesized and characterized. For radiopharmaceutical purposes, the (99m)Tc
      analogues have been prepared in a stepwise synthesis. Fluorescence microscopy
      studies on PC-3 cells, bearing the BBN receptor, showed high and rapid uptake
      into the cytoplasm. For the bifunctional molecule, lacking the BBN peptide, no
      internalization was observed.

PMID- 21186395
TI  - On the enantioselectivity of aziridination of styrene catalysed by copper
      triflate and copper-exchanged zeolite Y: consequences of the phase behaviour of
      enantiomeric mixtures of N-arene-sulfonyl-2-phenylaziridines.
AB  - By synthesising S-2-phenyl-N-(4-nitrophenyl)aziridine from S-phenylglycinol, it
      has been demonstrated that the aziridination of styrene by [N-(4
      nitrobenzenesulfonyl)imino]phenyliodinane (nosyliminophenyliodinane, PhINNs) in
      the presence of S,S-2,2'-isopropylidene-bis(4-phenyl-2-oxazoline), catalysed by
      copper(II) triflate in CH(3)CN solution or heterogeneously by CuHY, has
      predominantly an R-configuration. The enantioselectivity of the aziridination of
      styrene by [N-arenesulfonylimino]-phenyliodinanes catalysed by copper-exchanged
      zeolite Y (CuHY), in conjunction with a chiral bis-oxazoline ligand, has been re
      examined. In the case of PhINNs, it is shown that the product mixture of
      enantiomeric aziridines, on treatment with hexane, gives rise to a solid phase of
      low enantiomeric excess (ee) and a solution phase of high ee. Separation of the
      solid phase and recrystallisation afforded a true racemate (racemic compound),
      which has been confirmed by X-ray crystallography. The aziridine obtained from
      the solution phase could be recrystallised to produce the pure enantiomer
      originally in excess. A consequence of the new findings is that previous reports
      on the enantioselectivity of copper-catalysed aziridination, both in
      heterogeneous and homogeneous conditions, should be regarded with caution if the
      analytical procedure involved HPLC with injection of the enantiomeric mixture in
      a hexane-rich solvent. Such a method has been used in previous work from this
      laboratory, but has also been used elsewhere, following the procedure developed
      by Evans and co-workers when the (homogeneous) copper-catalysed aziridination by
      PhINTs was first discovered. Evidently, the change of substituent in the
      benzenesulfonyl group reduces the solubility in hexane, affording a solution
      phase of enhanced ee.

PMID- 21186396
TI  - Rapid and practical synthesis of (-)-1-deoxyaltronojirimycin.
AB  - Herein a practical and scalable route to 1-deoxyaltronojirimycin is presented.
      The target is achieved in 9 steps and 43% yield featuring only two
      chromatographic purifications.

PMID- 21186397
TI  - Synthesis, characterization and antioxidant activity of angiotensin converting
      enzyme inhibitors.
AB  - Angiotensin converting enzyme (ACE) catalyzes the conversion of angiotensin I
      (Ang I) to angiotensin II (Ang II). ACE also cleaves the terminal dipeptide of
      vasodilating hormone bradykinin (a nonapeptide) to inactivate this hormone.
      Therefore, inhibition of ACE is generally used as one of the methods for the
      treatment of hypertension. 'Oxidative stress' is another disease state caused by
      an imbalance in the production of oxidants and antioxidants. A number of studies
      suggest that hypertension and oxidative stress are interdependent. Therefore, ACE
      inhibitors having antioxidant property are considered beneficial for the
      treatment of hypertension. As selenium compounds are known to exhibit better
      antioxidant behavior than their sulfur analogues, we have synthesized a number of
      selenium analogues of captopril, an ACE inhibitor used as an antihypertensive
      drug. The selenium analogues of captopril not only inhibit ACE activity but also
      effectively scavenge peroxynitrite, a strong oxidant found in vivo.

PMID- 21186398
TI  - Further investigations into the N-demethylation of oripavine using iron and
      stainless steel.
AB  - Further investigations into the direct synthesis of N-nororipavine from oripavine
      using iron powder under non-classical Polonovski conditions have been conducted.
      The stoichiometry, solvents and iron oxidation rates were found to have a
      dramatic effect on the rate of N-demethylation as well as product yield. Herein,
      we also present high-yield access to the N-demethylated product simply by
      employing stainless steel rather than iron powder as redox catalyst. To our
      knowledge, this is the first time stainless steel has been used to moderate the
      redox chemistry of iron in organic synthesis.

PMID- 21186399
TI  - Elevated expression of orexin receptor 2 (HCRTR2) in benign prostatic hyperplasia
      is accompanied by lowered serum orexin A concentrations.
AB  - In search for the new polypeptides responsible for energy homeostasis which are
      also involved in regulating the growth and function of the human prostate, we
      assessed the expression of orexins (OXs) and of orexin receptors (OXRs) in human
      normal prostate and in benign prostatic hyperplasia (BPH). Conventional RT-PCR
      revealed the expression of OXR2 in all studied samples obtained either from
      normal prostates or BPH ones while neither preproorexin (ppOX)nor OXR1 mRNA were
      detected. In adenomatous prostates, expression levels of OXR2 were 30- to 40-fold
      higher compared to controls. Western blot analysis demonstrated the presence of
      OXR2 protein in the studied samples and its expression levels were 4-fold higher
      in tissue samples from BPH. In normal glands, presence of OXR2-like
      immunoreactivity was found in the apical parts of epithelial cells as well as in
      smooth muscle cells of the stroma. Immunostaining for OXR2 was more intense in
      sections obtained from BPH. Immunohistochemistry did not detect the expression of
      OXR1-like protein. OXA serum concentrations were lowered in BPH patients (mean +/
      SE 56+/-4 ng/ml, n=12; P<0.01) and unaltered in prostate cancer (79+/-7 ng/ml,
      n=18) compared to the controls (69+/-2 ng/ml, n=16). On the contrary, serum OXB
      levels were similar in all studied groups of patients. We thus have demonstrated
      the mRNA and protein expression of OXR2, but not of ppOX and OXR1 in both normal
      and BPH human prostate glands. We also demonstrated notable up-regulation of OXR2
      in benign prostatic hyperplasia, an alteration accompanied by lowered serum OXA
      concentrations. These findings suggest that both OXA and OXR2 may be involved in
      the pathogenesis and/or maintenance of BPH.

PMID- 21186400
TI  - Role of endogenous cholecystokinin on growth of human pancreatic cancer.
AB  - Cholecystokinin (CCK) and gastrin stimulate growth of pancreatic cancer. Although
      down-regulation of gastrin inhibits growth of pancreatic cancer, the contribution
      of endogenous CCK to tumor growth is unknown. The purpose of this study was to
      evaluate the role of endogenous CCK on autocrine growth of pancreatic cancer.
      Pancreatic cancer cell lines were analyzed for CCK mRNA and peptide expression by
      real-time RT-PCR and radioimmunoassay, respectively. The effect of endogenous CCK
      on growth was evaluated by treating cancer cells with CCK neutralizing antibodies
      and by down-regulating CCK mRNA by RNAi. Wild-type pancreatic cancer cells
      expressed significantly lower CCK mRNA and peptide levels than gastrin. Neither
      treatment of pancreatic cancer cells with CCK antibodies nor the down-regulation
      of CCK mRNA and peptide by shRNAs altered growth in vitro or in vivo. Conversely,
      when gastrin mRNA expression was down-regulated, the same cells failed to produce
      tumors in spite of having sustained levels of endogenous CCK. Pancreatic cancer
      cells produce CCK and gastrin; however, the autocrine production of gastrin is
      more important for stimulating tumor growth.

PMID- 21186401
TI  - Adenovirus-mediated Drosophila melanogaster deoxyribonucleoside kinase mutants
      combined with gemcitabine harbor a safe cancer treatment profile.
AB  - The purpose of this analysis was to investigate the enzyme activity and
      specificity of adenovirus-mediated Drosophila melanogaster deoxyribonucleoside
      kinase (Dm-dNK) mutants in combination with gemcitabine. Compared to herpes
      simplex type 1 thymidine kinases (HSV-TK) and other known dNKs, this Dm-dNK
      enzyme has a broader substrate specificity and a higher catalytic rate. We
      created the Dm-dNK mutants (dNKmut) by site-directed mutagenesis at the sites of
      244E, 245S, 251S, and 252R, with the last 10 amino acids in the amino acid
      sequence randomly alternated. We subsequently evaluated the enzyme activity and
      substrate specificity. The engineered enzymes showed a relative increase in
      phosphorylation in the nucleoside analogs of gemcitabine (dFdC, 2',2'-difluoro
      deoxycytidine) compared to the wild-type enzyme. The dNKmut enzymes were
      expressed in breast (Bcap37) and gastric (SGC-7901) cancer cell lines. In
      studying the sensitivity of the cell lines to dFdC, conditionally replicative
      adenovirus (CRAd) ZD55-dNKmut showed higher expression and enzymatic activity
      than the replication-defective adenovirus Ad-dNKmut in cancer cells, but with
      less cytotoxicity to cancer cells than that of Ad-dNKmut. Our data suggest that
      the triple phosphorylated dFdC catalyzed by dNKmut inhibited the replication of
      adenovirus with a simultaneous positive therapeutic effect on cancer cells.
      Therefore, concomitant use of the ZD55-dNKmut and dFdC could be a novel targeted
      strategy in suicide gene therapy with safe control of excessive virus
      replication.

PMID- 21186402
TI  - The chemosensitizing activity of inhibitors of glucosylceramide synthase is
      mediated primarily through modulation of P-gp function.
AB  - Glucosylceramide synthase (GCS) is a key enzyme engaged in the biosynthesis of
      glycosphingolipids and in regulating ceramide metabolism. Studies exploring
      alterations in GCS activity suggest that the glycolase may have a role in
      chemosensitizing tumor cells to various cancer drugs. The chemosensitizing effect
      of inhibitors of GCS (e.g. PDMP and selected analogues) has been observed with a
      variety of tumor cells leading to the proposal that the sensitizing activity of
      GCS inhibitors is primarily through increases in intracellular ceramide leading
      to induction of apoptosis. The current study examined the chemosensitizing
      activity of the novel GCS inhibitor, Genz-123346 in cell culture. Exposure of
      cells to Genz-123346 and to other GCS inhibitors at non-toxic concentrations can
      enhance the killing of tumor cells by cytotoxic anti-cancer agents. This activity
      was unrelated to lowering intracellular glycosphingolipid levels. Genz-123346 and
      a few other GCS inhibitors are substrates for multi-drug resistance efflux pumps
      such as P-gp (ABCB1, gP-170). In cell lines selected to over-express P-gp or
      which endogenously express P-gp, chemosensitization by Genz-123346 was primarily
      due to the effects on P-gp function. RNA interference studies using siRNA or
      shRNA confirmed that lowering GCS expression in tumor cells did not affect their
      responsiveness to commonly used cytotoxic drugs.

PMID- 21186403
TI  - The enhancement of propyl gallate-induced apoptosis in HeLa cells by a proteasome
      inhibitor MG132.
AB  - Propyl gallate (PG) used in processed food and medicinal preparations has been
      shown to induce cell death in normal and cancer cells. The inhibition of
      proteasome function has emerged as a useful strategy to maneuver apoptosis. Here,
      we investigated the combined effects of PG and MG132 (a proteasome inhibitor) on
      HeLa cells in relation to cell growth, cell death, reactive oxygen species (ROS)
      and glutathione (GSH). PG induced growth inhibition and apoptosis in HeLa cells,
      accompanied by the loss of mitochondrial membrane potential (MMP; DeltaPsim),
      activation of caspase 3 and PARP cleavage. The levels of ROS and GSH depletion
      were increased in PG-treated HeLa cells. MG132 intensified apoptosis and PARP
      cleavage in PG-treated HeLa cells. MG132 also increased ROS levels including
      mitochondrial O2*-, MMP (DeltaPsim) loss and GSH depletion in PG-treated HeLa
      cells. PG induced a G1 phase arrest of the cell cycle in HeLa cells, which was
      significantly prevented by MG132. MG132 alone inhibited HeLa cell growth via
      inducing the cell cycle arrests and triggering apoptosis. Conclusively, the
      inhibition of proteasome by MG132 plays a role as an enhancement factor in PG
      induced apoptosis of HeLa cells via increasing ROS levels and GSH depletion.

PMID- 21186404
TI  - Overexpression of Tiam1 predicts poor prognosis in patients with esophageal
      squamous cell carcinoma.
AB  - Accumulating evidence has demonstrated that T-cell lymphoma invasion and
      metastasis 1 (Tiam1) plays an important role in the occurrence and development of
      several different tumors; however, to date, little research has been done to
      verify the potential role of Tiam1 as a prognostic marker for esophageal squamous
      cell carcinoma (ESCC). In the present study, we examined the expression of Tiam1
      in ESCC tissues by immunohistochemistry, in situ hybridization, semi-quantitative
      RT-PCR and Western blotting methods and investigated the correlation between
      Tiam1 levels and prognosis of patients with ESCC. Tiam1 exhibited high expression
      in ESCC tissues, whereas the normal esophageal tissues showed negative or weak
      Tiam1 expression. Additionally, Tiam1 mRNA and protein expression levels were
      both significantly correlated with histology grade, clinical staging and lymph
      node metastasis (all P<0.05), but not related to age and gender (both P>0.05).
      Further, ESCC patients with strong Tiam1 mRNA (P=0.000) and protein (P=0.000)
      expression had a poorer prognosis than those with weak expression. These findings
      demonstrate that Tiam1 may be used as molecular marker for predicting the
      prognosis of patients with ESCC.

PMID- 21186405
TI  - [Enteral nutritional therapy in Crohn disease complicated with incomplete
      intestinal obstruction].
AB  - OBJECTIVE: To investigate the efficacy of enteral nutrition(EN) therapy for
      active Crohn disease(CD) complicated with incomplete intestinal obstruction.
      METHODS: Clinical data of 37 patients with active CD complicated with incomplete
      intestinal obstruction treated with EN(n=37) between January 2003 and September
      2009 were retrospectively analyzed. CD activity index (CDAI) was between 150 and
      450. The patients received total enteral nutrition (TEN) 125 kJ/kg by nasogastric
      tube or percutaneous endoscopic gastrostomy/jejunostomy(PEG/J) tube. Clinical
      response was defined as a decrease in CDAI>=70 from baseline since EN therapy,
      and clinical remission was defined as CDAI<150. Nutritional status, disease
      activity index, and side effects were recorded at the 0, 4th, and 12th week after
      EN therapy. RESULTS: Stricture or stenosis location included ileum in 8 (21.6%)
      patients, ileocolon in 19(51.4%), colon in 4(10.8%), jejunoileum in 5(13.5%), and
      duodenum in 1(2.7%). At 4 weeks after EN, CDAI significantly decreased(112.0+/
      39.6 vs.174.6+/-34.7,P<0.05). The ratio of clinical response was 43.2%(16/37) and
      clinical remission was 72.9%(27/37). At 12 weeks, CDAI was 70.2+/-32.9, lower
      than that at week 4(P<0.05). The ratio of clinical response was 70.2%(26/37) and
      clinical remission was 78.4%(29/37). Other disease activity indexes such as C
      reactive protein, erythrocyte sedimentation rate, and nutritional status such as
      BMI, serum albumin, prealbumin, transferrin and hemoglobin showed similar trend.
      During therapy, 7 cases had progressive intestinal obstruction resulting in bowel
      resection, 11 cases had diarrhea and/or abdominal distention due to inadequate
      infusion of home EN whose symptoms were improved after correction by the doctor.
      CONCLUSIONS: EN therapy can induce clinical response and remission in CD
      complicated with incomplete intestinal obstruction, relieve obstruction,
      alleviate the inflammatory response which plays positive role in the treatment of
      CD.

PMID- 21186406
TI  - [Comparative study on four different reconstruction procedures after total
      gastrectomy].
AB  - OBJECTIVE: To investigate the optimal reconstruction technique after total
      gastrectomy. METHODS: A total of 159 patients with gastric cancer undergoing
      total gastrectomy in Tianjin Cancer Hospital between January 2005 and December
      2007 were divided into 4 groups according to the reconstruction technique: group
      A(functional jejunal interposition with a pouch, n=46), group B(modified Braun
      type II(, n=38), group C (P pouch with Roux-en-Y esophagojejunostomy, n=25),
      group D(Roux-en-Y esophagojejunostomy, n=50). Quality of life(QOL), nutritional
      status 1 year after surgery, and perioperative complications were analyzed.
      RESULTS: There were no significant differences in perioperative
      complications(P>0.05). One year after operation, QOL(Visick index) was better in
      group A than that in group B, C and D(P<0.05), and group D was inferior to group
      A, B and C(P<0.05). The increase in food intake, weight gain, hemoglobin and
      total protein were better in group A than those in group B, C and D(P<0.05) and
      group D was inferior to group A, B and C(P<0.05). The prognostic nutrition index
      ratio of the four groups were 1.21+/-0.15, 1.14+/-0.97, 1.15+/-0.16, and 1.10+/
      0.16, respectively. Group A was better than that in group B, C and D (P<0.05) and
      group D was inferior to group A, B and C(P<0.05). The incidences of dumping
      syndrome, reflux esophagitis, Roux-en-Y stasis syndrome in group A were
      4.3%(2/46), 2.2%(1/46) and 2.2%(1/46), respectively, which were significantly
      lower than those in other groups (P<0.05). CONCLUSIONS: Functional jejunal
      interposition with a pouch is associated with improved nutritional condition and
      quality of life, and less perioperative complications. It is a reasonable
      reconstruction method after total gastrectomy.

PMID- 21186407
TI  - [Comparative study of laparoscopic-assisted radical gastrectomy versus open
      radical gastrectomy for early gastric cancer].
AB  - OBJECTIVE: To evaluate laparoscopic radical gastrectomy for early gastric cancer.
      METHODS: A total of 204 patients with early gastric cancer undergoing
      laparoscopic-assisted radical gastrectomy or open radical gastrectomy between
      October 2004 and December 2009 were retrospectively reviewed and analyzed.
      Patients were divided into laparoscopic group(LAP, n=78) and open group (OPEN,
      n=126). Operative time, blood loss, time to passage of flatus, postoperative
      hospital stay, complications and pathologic findings were compared between the
      two groups. RESULTS: Compared to the OPEN group, operative time in the LAP group
      was significantly shorter[(202.9+/-45.6) min vs.(219.8+/-45.2) min, P<0.05],
      blood loss was less[(144.5+/-146.5) ml vs. (245.0+/-146.4) ml, P<0.05], time to
      passage of flatus was shorter[(3.1+/-1.1) d vs.(4.5+/-1.6) d, P<0.05],
      postoperative hospital stay was shorter[(10.8+/-1.2) d vs. (12.4+/-3.8) d,
      P<0.05]. However, the two groups were comparable with regard to postoperative
      complication rate(10.3% vs. 12.7%, P>0.05), proximal resection margin[(4.0+/-1.9)
      cm vs. (4.2+/-1.7) cm, P>0.05], distal resection margin [(3.6+/-1.7) cm vs.
      (3.5+/-1.8) cm, P>0.05], number of harvested lymph node(13.1+/-6.5 vs. 14.5+/
      8.2, P>0.05). The median follow up was 22(2-64) months. There were no tumor
      recurrences or metastases in the LAP group. In the OPEN group, only 1 patient
      died from peritoneal metastasis. Total hospital costs between the two groups were
      similar(P>0.05). CONCLUSION: Laparoscopic radical gastrectomy is a safe,
      feasible, effective, and less invasive surgery for early gastric cancer.

PMID- 21186408
TI  - [Comparison of clinicopathological characteristics and prognosis of mucinous and
      poorly differentiated gastric cancer].
AB  - OBJECTIVE: To investigate the clinicopathological characteristics between
      mucinous gastric cancer (MGC) and poorly differentiated gastric cancer(PDGC) and
      factors associated with prognosis. METHODS: Medical records of 1016 consecutive
      patients with gastric cancer were retrospectively reviewed. Sixty-eight patients
      with MGC and 508 with PDGC were identified. Clinicopathologic characteristics and
      overall survival data were analyzed. RESULTS: As compared to PDGC patients,
      patients with MGC were significantly older [(59.2+/-11.9) years vs. (54.1+/-13.2)
      years], had significantly more distant metastasis(36.8% vs. 23.8%), more
      peritoneal seeding(29.4% vs. 16.9%), and less radical resection(60.3% vs. 76.6%).
      There were no significant differences in 5-year survival rate between MGC and
      PDGC patients(29.4% vs. 35.5%). However, for tumors in the middle third of the
      stomach, the survival rate of MGC patients was lower than that of PDGC. Using a
      Cox proportional hazard ratio model, lymph node involvement and radical resection
      were independent prognostic factors for survival of MGC patients, while tumor
      invasion, lymph node involvement, and radical resection were associated with
      survival in patients with PDGC. CONCLUSION: Although MGC and PDGC differ in age,
      frequencies of peritoneal seeding, distant metastasis, and rate of radical
      resection, overall survival is comparable.

PMID- 21186409
TI  - [Efficacy observation after pylorus-preserving gastrectomy for early gastric
      cancer].
AB  - OBJECTIVE: To evaluate the outcomes after pylorus-preserving gastrectomy (PPG)
      for early gastric cancer(EGC). METHODS: Clinicopathologic data of 52 patients
      with EGC undergoing PPG between August 1995 and December 2005 were analyzed
      retrospectively. A total of 159 patients of EGC who underwent distal gastrectomy
      with lymph node dissection(control group) were compared with those who received
      PPG. RESULTS: The lymph node metastasis rate of EGC was 9.6% in PPG group,
      including 9.6% in No.3, 3.9% in No.4, 3.9% in No.6, and 3.9% in No.7. In the
      control group, the lymph node metastasis rate was 17.0%, including N1(14.5%) and
      N2(2.5%). There were no significant differences between the PPG group and the
      control group (P>0.05). In the PPG group, D1 dissection was 25%, D1+alpha was
      25%, D1+beta was 34.6%, and D2 was 15.3%. In control group, 121 patients(76.1%)
      had less than D2 dissection, while there were 33(20.7%) D2, and 5(3.1%) D3, and
      the difference was not statistically significant(P>0.05). There were no
      significant differences between the two groups in overall 5-year survival
      rate(92.3% vs. 93.1%, P=0.881). The 5-year survival rate in the PPG group was
      100% for D1, 92.3% for D1+alpha, 88.9% for D1+beta, and 85.7% for D2, while the 5
      year survival rate in the control group was 92.3% for D1, 93.3% for D1+alpha,
      91.7% for D1+beta, and 93.9% for D2. The difference was not statistically
      significant(P>0.05). The recurrence rate was comparable (5.7% vs. 5.6%, P>0.05).
      CONCLUSION: Pylorus-preserving gastrectomy may provide long-term survival
      benefits for patients with early gastric cancer.

PMID- 21186410
TI  - [Analysis of 32 patients with rectal adenoma undergoing transanal endoscopic
      microsurgery].
AB  - OBJECTIVE: To evaluate the safety and outcomes after transanal endoscopic
      microsurgery (TEM)for rectal adenoma. METHODS: Data of 32 patients undergoing TEM
      for rectal adenoma between September 2006 and February 2010 in the Ruijin
      Hospital were reviewed. RESULTS: The adenoma diameter ranged from 0.6 to
      10.0(2.3+/-1.2) cm. The mean operative time was 70(range,20-180) min. The
      estimated blood loss was less than 10 ml. There were no conversions to
      transabdominal procedure. Twenty-two(68.8%) patients underwent suturing of the
      wound, of whom 14 had full-thickness resection. Two patients had perforation into
      peritoneal cavity during full-thickness resection, which were repaired by
      continuous suturing and no postoperative leak occurred. R0 resection was achieved
      in 31(96.9%) patients. Postoperative pathology showed 12 simple adenomas, 10
      adenomas with low grade intraepithelial neoplasia, 5 adenomas with high grade
      intraepithelial neoplasia, and 5 T1 focal carcinomas. Complications included
      rectal bleeding in 1 patient, acute urinary retention in 1 patient, and pulmonary
      infection in 1 patient. The postoperative stay was 4.5(3-8) days. The patients
      were followed-up for a period of 23 months(range, 2-43 months). There were 2
      tumors recurred. CONCLUSION: TEM is a safe and effective minimally invasive
      surgical technique for large rectal adenomas.

PMID- 21186411
TI  - [Analysis of clinicopathologic features and prognosis in 2414 patients with
      rectal cancer].
AB  - OBJECTIVE: To explore the clinicopathologic factors associated with prognosis in
      patients with rectal cancer. METHODS: Clinicopathologic data of 2414 patients
      with rectal cancer, treated in the Affiliated Tumor Hospital of Harbin Medical
      University from May 1976 to December 2003, were analyzed retrospectively. Cox
      regression model was used to assess independent factors associated with
      prognosis. RESULTS: The median survival time was 58 months and the 5-year overall
      survival rate was 45.1%. Tumors were stage I( in 75.2%, stage II( in 48.1%, stage
      III( in 21.3%, and stage IV( in 8.8% of the patients. The 5-year overall survival
      rates during the three study periods were 41.2%(1976-1986), 43.0%(1987-1996), and
      49.1%(1997-2003)(P<0.01). On univariate analysis, age, time at diagnosis,
      histological type, distant metastasis, type of surgery, intent of surgery, gross
      morphology, pathologic T stage, lymphatic invasion, bowel obstruction, and TNM
      stage showed statistically significant association with survival. Independent
      prognostic factors on multivariable analysis were gross tumor morphology chi
      squared value(CV):68.744, pT(CV:81.344), lymphatic invasion(CV:42.951), bowel
      obstruction(CV:37.856) and TNM stage(CV:85.329). CONCLUSIONS: Survival in
      patients with rectal cancer is improved over time. TNM stage is the most
      important prognostic factor for survival in patients with rectal cancer.

PMID- 21186412
TI  - [Short-term efficacy of laparoscopic-assisted right hemicolectomy with D3 lymph
      node dissection in colon cancer].
AB  - OBJECTIVE: To explore the feasibility and short-term efficacy of laparoscopic
      assisted D3 lymph node dissection for right colon cancer with a medial-to-lateral
      approach. METHODS: Clinical data of 61 patients with right colon cancer
      undergoing D3 lymph node dissection from March 2006 to June 2010 were analyzed
      retrospectively. Among them,29 underwent laparoscopic-assisted right
      hemicolectomy (LARH group) and 32 underwent open right hemicolectomy (ORH group).
      The number of lymph node harvest, operative details, and complication rate were
      compared between the two groups. RESULTS: The mean number of lymph node harvest
      did not differ significantly between the two groups (16.9+/-3.8 vs. 15.4+/-3.6).
      As compared to ORH group, although the operative time was significantly longer
      [(214.4+/-37.9) min vs. (193.3+/-28.8) min] in LARH group, the mean blood loss
      [(83.4+/-38.0) ml vs. (192.7+/-43.6) ml], time to first flatus [(44.6+/-20.8) h
      vs. (70.4+/-80.0) h], time to resumption of soft diet[(32.5+/-10.6) h vs. (59.7+/
      10.4) h], and postoperative hospital stay [(11.2+/-2.2) d vs. (13.8+/-2.8) d]
      were more favorable(all P<0.05). Complication rate was lower in LARH group(10.4%
      vs. 9.4%), however the difference was not statistically significant. CONCLUSIONS:
      LARH with D3 lymph node dissection is oncologically comparable with ORH for right
      colon cancer. It is a safe and feasible procedure associated with rapid
      postoperative recovery.

PMID- 21186414
TI  - [Surgical approach for upper gastric cancer].
AB  - OBJECTIVE: To investigate the reasonable surgical approach for upper gastric
      cancer, surgical technique, and indications for combined resection of the spleen.
      METHODS: Eight hundred and three patients with upper gastric cancer were operated
      in the Cancer Center of Sun Yat-Sen from December 1964 to December 2004,
      including 341 cases undergoing abdominal incision and 462 thoracotomy or abdomino
      thoracic incision. Clinical data were analyzed retrospectively. RESULTS: The
      operative time was significantly shorter in the abdominal incision group (170 vs.
      220 min, P<0.01), as was the transfusion volume (200 vs. 650 ml, P<0.05).
      Positive resection margin was similar between the two groups (5.6% vs. 6.7%,
      P>0.05). There was no difference in overall postoperative complication rate (3.2%
      vs. 5.0%, P>0.05). Length of hospital stay was shorter in the abdominal incision
      group (21 vs. 26.6 days, P<0.05). CONCLUSION: Selection of surgical approach
      should be based on the tumor characteristics. Abdominal incision should be the
      approach of choice where possible.

PMID- 21186413
TI  - [Symptom analysis of 537 patients with neurogenic intrapelvic syndrome].
AB  - OBJECTIVE: To characterize the symptoms of neurogenic intrapelvic syndrome and
      the pathogenic mechanisms. METHODS: A total of 537 patients with neurogenic
      intrapelvic syndrome were treated in the Takano Hospital between 2001 and 2005.
      Clinical data were analyzed retrospectively. RESULTS: The mean age was 58.5 years
      old. There were 205 males and 332 females. There were 80 patients(14.9%) who
      presented with only one symptom with anorectal pain being the most common one
      (43.8%, 35/80). One hundred and fifty-six(29.1%) patients had two symptoms with
      anorectal pain and difficult evacuation being the most common combination (26.3%,
      41/156). There were 144 patients (26.8%) complained of 3 symptoms and the most
      common combination was anorectal pain, difficult evacuation, and abdominal
      discomfort (30.0%, 43/144). A combination of 4 symptoms was reported in 105
      patients(19.6%) with the combination of anorectal pain, incontinence, abdominal
      discomfort, and lumbar discomfort being the most often(65.7%, 69/105). In
      addition, there were 52 patients(9.7%) who had above 5 symptoms simultaneously.
      The frequencies of the 5 symptoms were 73.6% for anorectal pain, 27.9% for
      incontinence, 69.6% for difficult evacuation, 55.3% for abdominal discomfort, and
      53.6% for lumbar discomfort. CONCLUSIONS: Symptomatology of neurogenic
      intrapelvic syndrome is complicated. The pathogenic mechanism may be related to
      concurrent dysfunction of sacral nerve and pelvic splanchnic nerve.

PMID- 21186415
TI  - [Role of integrin alpha4beta7 in the pathogenesis of ulcerative colitis in rats].
AB  - OBJECTIVE: To investigate the role of integrin alpha4beta7 in the development of
      ulcerative colitis (UC) in rats. METHODS: Sixty Sprague-Dawley rats were randomly
      divided into the control group (acetone enema), the model group (2,4
      dinitrochlorobenzene, DNCB enema), and the alpha4 intervention group. Colonic
      mucosa of different groups was observed and compared in terms of pathology and
      cytokine changes(IL-2 and IL-6) using ELISA. Semi-quantitative RT-PCR was used to
      detect the colon alpha4beta7 expression. Integrin alpha4beta7(+) lymphocytes in
      the portal vein of rats were determined by flow cytometry. RESULTS: The
      expression of alpha4 mRNA was 0.68+/-0.24 in the model group and 0.58+/-0.37 in
      the intervention group, and the expression of beta7 mRNA was 0.84+/-0.37 in the
      model group and 0.65+/-0.30 in the intervention group, which were all
      significantly higher as compared to those in the control group(0.15+/-0.13 for
      alpha4 and 0.24+/-0.62 for beta7, P<0.01). The proportions of integrin
      alpha4beta7 positive lymphocytes in the portal vein in the model group and
      intervention group were significantly higher than that in the control group
      [(76.7+/-8.2)% and (68.2+/-7.6)% vs. (14.7+/-6.7)%, P<0.01]. The expression of IL
      2 and IL-6 and the result of macroscopic and microscopic scores in the
      intervention group were lower than those in the model group(P<0.05). CONCLUSIONS:
      High expression of alpha4beta7 may play an important role in experimental colon
      mucosa inflammation in rats with ulcerative colitis. The blockade of integrin
      alpha4beta7 may be a potential target to reduce colonic mucosa inflammation.

PMID- 21186416
TI  - [Experimental research of integral continuous jejunal interposition after
      subtotal distal gastrectomy].
AB  - OBJECTIVE: To evaluate nutritional status, myoelectrical activity, and
      gastrointestinal tract emptying capacity after integral continuous jejunal
      interposition following subtotal gastrectomy. METHODS: According to different re
      construction techniques, 30 Beagle dogs were divided into four groups after
      subtotal distal gastrectomy: group 1(n=9, integral continuous jejunal
      interposition), group 2(n=6, Billroth I(), group 3(n=7, Billroth II(), group
      4(n=8, isolated jejunal interposition). Blood cell counts, liver function,
      myoelectrical activity and the rate of gastrointestinal tract emptying were
      compared among the four groups. RESULTS: At week 12 after operation, the body
      weight in group 1 [(9.65+/-1.54) kg] was significantly higher than that in group
      2[(9.25+/-1.76)kg], group 3[(9.31+/-1.54)kg] and group 4[(7.77+/-1.46)kg]. At
      week 4, the prognostic nutritional index in group 1(2671.9+/-49.9) was
      significantly higher than that in group 3(2555.9+/-54.7) and group 4(2440.9+/
      54.3), but similar to that in group 2(2791.8+/-54.3). At week 6, the fasting and
      postprandial frequency of jejunal pacesetter potentials in group 1 were higher
      than those in group 3 and group 4(P<0.05) but comparable with those in group 2.
      The emptying rate of food in the four groups were 95.4%, 91.3%, 93.1% and 94.2%,
      respectively and there were no significant differences(P>0.05). However, as
      compared with group 2 and group 3, group 1 had longer operative time and later
      regular diet resumption, more severe abdominal adhesion(P<0.05). CONCLUSION:
      Continuous jejunal interposition should be considered when Billroth I( is not
      feasible after subtotal gastrectomy.

PMID- 21186417
TI  - [Impact of 5-fluorouracil on glucose metabolism and pancreatic pathology in
      rats].
AB  - OBJECTIVE: To explore the impact of 5-fluorouracil (5-FU) on glucose metabolism
      and pancreatic pathology. METHODS: Twenty Wistar rats were divided into 5-FU
      group(n=10, chemotherapy was administered intraperitoneally to animals at a dose
      of 20 mg/kg daily for continuous 5 days) and control group (n=10, sodium chloride
      was administered intraperitoneally to animals with the same dose at the same time
      ). Glucose tolerance was evaluated 2 and 7 days following 5-FU treatment by
      serial measurement of blood glucose before and after an oral glucose load. Plasma
      insulin concentration was determined by radioimmunoassay. Pancreatic pathology
      was examined with morphological method and the ultrastructural changes of beta
      cells were observed by transmission electron microscope. RESULTS: Fasting blood
      glucose level was significantly higher in the 5-FU group than that in the control
      group [(7.6+/-0.9) mmol/L vs. (4.6+/-0.6) mmol/L at day 2; (8.9+/-1.0) mmol/L vs.
      (4.7+/-0.6) mmol/L at day 7, P<0.01]. Insulin releasing test indicated that the
      early phase insulin response to glucose load was significantly diminished in
      animals treated with 5-FU at day 2. Insulin level was significantly lower in the
      5-FU group than that in the control group at 30 min (P<0.01). The peak secretion
      time of plasma insulin in 5-FU group was at 60 min, similar to the control group;
      and plasma insulin level decreased more slowly. Plasma insulin level was higher
      in 5-FU groups than in control groups on 120 min and 180 min. At day 7, Insulin
      level was lower in the 5-FU group than that in the control group on 60 min, and
      the peak secretion time of plasma insulin was delayed to 120 min. Plasma insulin
      level was significantly increased in 5-FU group than that in control group on 180
      min(P<0.01). No gross histopathological damage to the pancreas was observed at
      day 2 and 7 following administration of 5-FU. The structural changes of
      mitochondria were mainly the quantities of secretory granule diminished at day 7
      under transmission electron microscope. Dilated rough endoplasmic reticula,
      swollen mitochondria, and the presence of adipose drops in lysosomes were found
      in few cells. CONCLUSIONS: 5-FU-induced hyperglycemia appears to be mediated in
      part by a relatively deficient insulin secretion to glucose stimulation. A
      relative deficiency in insulin secretion following 5-FU treatment appears to be
      related to beta cells function impairs with islet cell ultrastructural changes
      induced by 5-FU.

PMID- 21186422
TI  - Oil on the water in the Gulf of Mexico.

PMID- 21186423
TI  - Fish consumption and concentrations of polybrominated diphenyl ethers (PBDEs) in
      the serum of older residents of upper Hudson River communities.
AB  - A study was conducted to evaluate exposure to polybrominated diphenyl ethers
      (PBDEs) among 144 men and women 55 to 74 years residing along the Hudson River.
      The results indicated a median serum PBDE concentration of 23.9 ng/g lipid wt.
      This value is similar to those of other New York State studies of populations
      that are younger and proportionately more likely to be male, suggesting that
      pathways do not differ by age or sex. Individual congeners were highly
      correlated, but they were not associated with concentrations of polychlorinated
      biphenyls (PCBs). Persons with a body mass index (BMI) > 30 had a geometric mean
      SigmaPBDE concentration of 46.7 versus 25.2 ng/g lipid wt for persons with a BMI
      <= 30 (p = .006). Fresh water fish consumption was not associated with serum PBDE
      concentrations in this population.

PMID- 21186424
TI  - Lung function and respiratory symptoms in male Palestinian farmers.
AB  - In a cross-sectional study of 250 farmers aged 22 to 77 years, of whom 36.4% are
      smokers, the authors aimed at describing lung function and respiratory symptoms
      and to estimate associations with exposures to pesticides and dust. Lung function
      was measured using a spirometer. Respiratory symptoms and exposure levels were
      self-reported based on a modified standardized questionnaire. Mean forced vital
      capacity (FVC) was 4.20 L (SD = 0.93 L), 95.51% of predicted as compared to
      European standards. Mean forced expiratory volume in one second (FEV(1)) was 3.28
      L (SD = 0.80 L), 91.05% of predicted. The authors found high symptom prevalences:
      14.0% for chronic cough; 26.4% for wheeze; and 55.2% for breathlessness. There
      was no clear association between exposure to pesticides or dust and lung function
      or between such exposures and respiratory symptoms. However, a significant
      association was found between smoking and respiratory symptoms such as chronic
      cough, cough with phlegm, and wheezes. The lack of farm exposure associations
      could be due to improvement in farmers' awareness to pesticides hazards as well
      as regulations of pesticide import, or because of inherent problems with the
      experimental design. Farmers who kept animals and poultry seem to have less
      respiratory symptoms and better lung function.

PMID- 21186425
TI  - Associations between atmospheric concentrations of spores and emergency
      department visits for asthma among children living in Montreal.
AB  - The authors carried out a time-series study to determine whether short-term
      increases in the concentrations of spores were associated with emergency
      department visits from asthma among children 0 to 9 years of age in Montreal,
      1994-2004. Concentrations of spores were obtained from one sampling monitor. The
      authors used parametric Poisson models to model the association between daily
      admissions to emergency rooms for asthma and ambient exposures to a variety of
      spores, adjusting for secular trends, changes in weather, and chemical
      pollutants. For first admissions and exposures to Basidiomycetes, the authors
      found positive associations at all lags but the concurrent day. For
      Deuteromycetes and Cladosporium, risks were positive starting at lag 3 days and
      diminished at lag 6 days. There was little evidence of associations for
      readmissions, except for Basidiomycetes. The results indicate that Basidiomycetes
      and Cladosporium spores may be implicated in the exacerbation of asthma among
      children, most notably in the case of first-time visits to emergency departments,
      and that the effects appear to be delayed by several days.

PMID- 21186426
TI  - DNA damage, glutathione, and total antioxidant capacity in anesthesia nurses.
AB  - The possibilities of a potential mutagenic/carcinogenic action of waste
      anesthetic gases in occupationally exposed anesthesia personnel have been
      previously reported in several studies. The aim of this study was to assess the
      DNA damage, reduced glutathione (GSH), and total antioxidant capacity (TAC) in
      anesthesia nurses. DNA damage was determined with comet assay, GSH levels were
      measured spectrophotometrically, and TAC was determined by using Randox kit.
      Anesthesia nurses (n = 40) showed increased DNA damage in terms of mean
      percentage of the total DNA in the comet tail compared to controls (n = 40) (p <
      .001). Mean TAC and GSH levels of the anesthesia nurses were significantly lower
      than that of the controls (p < .001, p < .05, respectively). The results of this
      study indicate that occupational exposure to anesthetic gases induce DNA damage,
      which may lead to changes in TAC and GSH levels.

PMID- 21186427
TI  - Upper body quadrant pain in bus drivers.
AB  - The aims of this study were to evaluate the prevalence of upper body quadrant
      pain among Israeli professional urban bus drivers and to evaluate the association
      between individual, ergonomic, and psychosocial risk factors and occurrence of
      neck pain. Three hundred and eighty-four male urban bus drivers were
      consecutively enrolled in the study. Data pertaining to work-related ergonomic
      and psychosocial stress factors were collected. The 12-month prevalence of neck
      pain was 21.2%, followed by shoulder: 14.7%, upper back: 8.3%, elbow: 3.0%, and
      wrist: 3.0% pain. Prevalence of neck pain was associated with uncomfortable seats
      (odds ratio; OR [95% confidence interval; CI]: 2.2 [1.2-4.3], back support (2.3
      [1.2-4.2]), and steering wheel (2.2 [1.1-4.5]). Drivers with neck pain reported
      significantly higher prevalence of pain in the upper back (OR [95% CI]: 5.9 [2.7
      12.9]), shoulders (8.1 [4.3-15.3]), and wrists (7.0 [2.0-21.8]) compared to
      drivers without neck pain. Work-related organizational stress factors were not
      associated with neck pain prevalence.

PMID- 21186428
TI  - The association between socioeconomic status and prevalence of diabetes mellitus
      in rural Japan.
AB  - The objective of this study is to investigate the association between
      socioeconomic status and diabetes prevalence. A population-based cross-sectional
      survey was conducted in Japan. The association between household income tertile,
      duration of education (<12, 12, >12 years), or occupation (blue collar, white
      collar) and diabetes prevalence were assessed in 6,197 participants using
      multivariable-adjusted logistic regression models. Blue collar occupation and
      middle household income were found to be associated with high prevalence of
      diabetes mellitus.

PMID- 21186429
TI  - Environmental hazards of waste disposal patterns--a multimethod study in an
      unrecognized Bedouin village in the Negev area of Israel.
AB  - The Bedouin of the Negev region of Israel are a formerly nomadic, indigenous,
      ethnic minority, of which 40% currently live in unrecognized villages without
      organized, solid waste disposal. This study, using both quantitative and
      qualitative methods, explored the transition from traditional rubbish production
      and disposal to current uses, the current composition of rubbish, methods of
      waste disposal, and the extent of exposure to waste-related environmental hazards
      in the village of Um Batim. The modern, consumer lifestyle produced both
      residential and construction waste that was dumped very close to households.
      Waste was tended to by women who predominantly used backyard burning for
      disposal, exposing villagers to corrosive, poisonous, and dangerously flammable
      items at these burn sites. Village residents expressed a high level of concern
      over environmental hazards, yet no organized waste disposal or environmental
      hazards reduction was implemented.

PMID- 21186430
TI  - Walt Whitman: an American Civil War nurse who witnessed the advent of modern
      American medicine.

PMID- 21186431
TI  - Celebrating a milestone in EOH: the pioneering first issue of the Journal of
      Industrial Hygiene, May 1919.

PMID- 21186433
TI  - Relationship between fatigue and photosensitivity.
AB  - It is considered that photosensitivity is one of the most important factors to
      cause video-game epilepsy. Since photosensitivity is thought to cause various
      signs of hypersensitivity in the central nervous system and hypersensitivity is
      believed to be related to fatigue, whether fatigue is associated with
      photosensitivity was determined. The study group consisted of 68 healthy medical
      students attending Osaka City University Graduate School of Medicine. They
      completed questionnaires dealing with fatigue (Chalder Fatigue Scale) and
      photosensitivity. On simple regression analyses, fatigue score was positively
      associated with photosensitivity score. Similarly, on multiple regression
      analyses adjusted for age, gender, and sleeping hours, fatigue score was
      positively associated with photosensitivity score. Fatigue is associated with
      photosensitivity. Our findings provide new perspectives on fatigue.

PMID- 21186434
TI  - The disconnected values model improves mental well-being and fitness in an
      employee wellness program.
AB  - This study examined the effect of a 10-week wellness program on changes in
      physical fitness and mental well-being. The conceptual framework for this study
      was the Disconnected Values Model (DVM). According to the DVM, detecting the
      inconsistencies between negative habits and values (e.g., health, family, faith,
      character) and concluding that these "disconnects" are unacceptable promotes the
      need for health behavior change. Participants were 164 full-time employees at a
      university in the southeastern U.S. The program included fitness coaching and a
      90-minute orientation based on the DVM. Multivariate Mixed Model analyses
      indicated significantly improved scores from pre- to post-intervention on
      selected measures of physical fitness and mental well-being. The results suggest
      that the Disconnected Values Model provides an effective cognitive-behavioral
      approach to generating health behavior change in a 10-week workplace wellness
      program.

PMID- 21186435
TI  - Relationship between family history of breast cancer and health-related behavior.
AB  - This article explores the relationship between family history of breast cancer
      (FHBC) and health-related behavior and medical management, using a cross
      sectional analysis of 685 women, based on self-report. The influence of FHBC on
      lifestyle (alcohol use, physical activity, weight and diet) and medical
      management decisions (screening for chronic diseases) was assessed using odds
      ratios (OR) and 95% confidence interval (CI). Adjustment for confounders was
      performed using unconditional logistic regression. Sixty five women (9.5%)
      reported relatives with breast cancer. Women with FHBC are more likely to have
      had a mammography and colonoscopy or sigmoidoscopy. These women have about twice
      the probability of performing more intense physical exercise, contrasting with
      high-risk women whose consumption of fibre is lower and sweets is higher. No
      significant association was found between alcohol consumption or Body Mass Index
      and family history. Spontaneous behavioral change to a more preventive lifestyle
      in relatives of cancer patients is very low.

PMID- 21186436
TI  - Use and evaluation of a CD-ROM-based decision aid for prostate cancer treatment
      decisions.
AB  - The survival advantages associated with different treatments for localized
      prostate cancer (PCa) continue to be uncertain. We evaluated patients' use of an
      interactive CD-ROM-based decision aid designed to improve informed decision
      making about PCa treatment. Newly diagnosed, early-stage PCa patients who had not
      made a treatment decision completed a baseline telephone interview (N = 132),
      were mailed the CD-ROM, and completed a one-month follow-up interview (N = 120;
      91%). Compared to non-users (21%), CD-users (79%) preferred to make an
      independent rather than a shared treatment decision (OR = 3.5, CI 1.2,10.5). The
      majority of users (63%-90%) responded positively regarding the length and clarity
      of the information. Further, 76% reported using the CD as much/more than other
      information sources. A preference for having less decisional control predicted
      greater satisfaction with the CD (F[7,87] = 4.75, p < .05). Electronic
      utilization data revealed that the topics most accessed concerned treatment
      information and that users spent over an hour using the CD (median = 72 minutes).
      This electronic educational tool was well-accepted by patients and may be
      particularly useful for patients who desire less control over their treatment
      decisions and who are less proactive in seeking information on their own.

PMID- 21186437
TI  - Correlates to long-term-care nurse turnover: survey results from the state of
      West Virginia.
AB  - The authors sought statistical correlates to long-term-care nurse turnover using
      surveys from 253 practicing nurses across 54 of 55 counties in West Virginia. A
      chi-square test for homogeneity showed significant relationships between select
      demographic variables and job-related dimensions categorized either as benefits
      (pay, schedule flexibility and growth opportunity, travel time to work, patient
      behavior, facility conditions, supervisor relations) or job-related dimensions
      categorized as costs (travel time to work, patient behavior, facility conditions,
      supervisor relations, and family needs). Five demographic characteristics:
      gender, education level, job title, county in West Virginia region, and facility
      size bore no relationship to any job-related dimension listed.

PMID- 21186438
TI  - Real healthcare reform: focus on primary care access.
AB  - Primary care coverage for the uninsured is the first necessary step to reform and
      can be more cost effective and tolerable than a major system reform. By providing
      foundational care to the uninsured, more care resources are targeted to those
      that most need the services, while providing benefits such as increased
      productivity and reduced inappropriate emergency department utilization. The
      authors aimed to design a primary care coverage system in the United States for
      the uninsured using established reimbursement, budgeting, and compliance methods.
      Providing four primary care visits for acute care, four associated ancillary and
      four fulfilled pharmaceutical-treatment prescriptions, and one preventive primary
      care visit per year for nearly 48,000,000 uninsured would cost $36 per month for
      every working American and legal alien resident. Theoretical and empirical
      literature was reviewed and the authors applied practical knowledge based on
      their experience in healthcare systems to develop the Access America Program.

PMID- 21186439
TI  - Performance of state medical boards: implications for hospitals and health
      systems.
AB  - The accountabilities and operations of state medical boards can have significant
      implications for hospitals and health systems in terms of their efforts to ensure
      quality care and patient safety. This study examined the performance of state
      medical boards and the reasons for variability in board performance by
      identifying factors impacting the performance of state medical boards in terms of
      physician discipline and those variables most critical to medical board
      performance. The findings suggested that increasing staff support and appointing
      lay board members would lessen the degree of variability in the performance of
      state boards although there remained a significant amount of variance to be
      explained.

PMID- 21186442
TI  - Should exercise be promoted as an effective intervention strategy to off-set
      excessive college student drinking?

PMID- 21186443
TI  - Characteristics associated with genital herpes testing among young adults:
      assessing factors from two national data sets.
AB  - OBJECTIVES AND PARTICIPANTS: in the United States, genital herpes (GH) prevalence
      is 10.6% among 20- to 29-year-olds and about 90% of seropositive persons do not
      know their status. This study investigated individual characteristics associated
      with GH screening and diagnosis in sexually active young adults aged 18 to 24.
      METHODS: two data sets were analyzed: the National Longitudinal Study of
      Adolescent Health (Add Health) Wave III from 2001 to 2002 (n = 11,570) and the
      American College Health Association's (ACHA's) national survey of college
      students from 2000 to 2006 (n = 222,470). RESULTS: in Add Health, 18.4% of
      females and 7.1% of males self-reported GH testing in the previous 12 months,
      compared to 0.7% for self-reported GH diagnosis in ACHA. GH testing and diagnosis
      was strongly positively associated with a history of human immunodeficiency virus
      (HIV) testing and diagnosis of sexually transmitted infections (STIs) in the
      previous 12 months for both sexes. CONCLUSIONS: integrating herpes screening and
      testing into HIV and standard STI screening would identify more infections.

PMID- 21186444
TI  - Screening and brief interventions for alcohol use in college health centers: a
      review.
AB  - OBJECTIVES: to provide a critical review of the efficacy of brief interventions
      for alcohol use in college health centers. METHODS: studies were included if (a)
      they examined brief intervention trials that were conducted in college- or
      university-based student health centers or emergency departments, and (b) they
      provided pre-post data to estimate change. RESULTS: twelve studies suggested that
      screening and brief interventions in these settings are acceptable, feasible, and
      promote risk reduction. CONCLUSIONS: findings support continued use of time
      limited, single-session interventions with motivational interviewing and feedback
      components.

PMID- 21186445
TI  - College students' exposure to tobacco marketing in nightclubs and bars.
AB  - OBJECTIVE: to examine whether a college student's exposure to tobacco marketing
      in nightclubs and bars was affected by the presence of a smoke-free law.
      PARTICIPANTS: a random sample (N = 478) of students participated in the survey
      (no smoke-free law, n = 240; smoke-free law, n = 238). The analysis was limited
      to students who reported being in nightclubs and bars (n = 171). METHODS: a
      nonexperimental, cross-sectional, 2-group design was used. RESULTS: students in
      the smoke-free law city were more likely to be approached by tobacco marketers
      (34.7% versus 20.2%, p = .02), offered free gifts (41.7% versus 24.2%, p = .02),
      and take free gifts for themselves (34.7% versus 19.2%, p = .02). They were more
      likely to be exposed to direct marketing strategies (1.83 versus 1.12, p = .02).
      There was no difference on indirect tobacco marketing by site. CONCLUSIONS:
      tobacco marketing is pervasive in nightclubs and bars. Smoke-free laws may
      protect against exposure to secondhand smoke but not the "pro" smoking messages
      students encounter.

PMID- 21186446
TI  - Mindfulness and health behaviors: is paying attention good for you?
AB  - OBJECTIVE: the investigators examined relations between mindfulness and health
      behaviors in college students, as well as the role of stress in mediating these
      effects. PARTICIPANTS: participants were 553 undergraduates (385 females; mean
      age = 18.8 years, SD = 2.1) recruited from a university in the northeastern
      United States. METHODS: participants completed questionnaires assessing
      mindfulness, perceived health, health behaviors, health-related activity
      restriction, and stress. Data were collected from September 2007 through December
      2007. RESULTS: overall perceived health and health-related activity restriction,
      as well as some health behaviors (eg, binge eating, sleep quality, and physical
      activity) were related to the Five-Factor Mindfulness Questionnaire and were
      partially mediated by stress. CONCLUSIONS: these results suggest that mindfulness
      is related to decreased stress, which in turn contributes to increased positive
      health perceptions and health behaviors. The findings support the utility of
      mindfulness in promoting physical and psychological health in college students.

PMID- 21186447
TI  - Prevalence of insomnia and its psychosocial correlates among college students in
      Hong Kong.
AB  - OBJECTIVE: this study examined the prevalence of insomnia and its psychosocial
      correlates among college students in Hong Kong. PARTICIPANTS: a total of 529 Hong
      Kong college students participated in the study. METHODS: participants completed
      a self-reported questionnaire that included the Pittsburgh Sleep Quality Index
      (PSQI), the Revised Life Orientation Test, the Perceived Stress Scale, and the
      Beck Depression Inventory, and questions about sociodemographic and lifestyle
      factors. A PSQI global score equal to or greater than 5 indicated insomnia.
      RESULTS: results indicated that 68.6% of the participants were insomniacs.
      Adjusted regression analyses revealed that optimism, stress, and depression
      significantly predicted insomnia (p < .01). CONCLUSIONS: these results suggest
      that insomnia is very common among Hong Kong college students and associated with
      other psychosocial factors. This study provides preliminary data on sleep quality
      and risk factors for insomnia, which may be used to guide sleep hygiene promotion
      and intervention among college students.

PMID- 21186448
TI  - Knowledge of human papillomavirus and perceived barriers to vaccination in a
      sample of US female college students.
AB  - OBJECTIVE: to assess knowledge of human papillomavirus (HPV) and perceived
      barriers to being vaccinated against the virus. PARTICIPANTS: three hundred
      ninety-six undergraduate women enrolled at Penn State University in Fall 2008.
      METHODS: a random sample of students were invited to participate in a Web-based
      survey. RESULTS: awareness of HPV and the vaccine was high, but knowledge of HPV
      related facts averaged only 65% overall. Knowledge was significantly predicted by
      frequency of media exposure and physician encouragement to be vaccinated, but not
      by the number of sex partners nor the frequency of condom/dental dam use. On
      average, women indicated that 2 of the 10 barriers listed applied to them.
      Physician encouragement negatively predicted barriers at p = .066. No other
      predictors approached significance. CONCLUSIONS: serious misconceptions remain
      about specific aspects of the diseases and how they are acquired. Health
      education efforts are needed to improve knowledge in college populations and
      counteract perceived barriers.

PMID- 21186449
TI  - Social norms of alcohol, smoking, and marijuana use within a Canadian university
      setting.
AB  - OBJECTIVE: to study actual and perceived substance use in Canadian university
      students and to compare these rates with US peers. PARTICIPANTS: students (N =
      1,203) from a large Canadian university. METHODS: participants were surveyed
      using items from the National College Health (NCHA) Assessment of the American
      College Health Association questionnaire. RESULTS: alcohol was the most common
      substance used (65.8%), followed by marijuana (13.5%) and cigarettes (13.5%).
      Substance use and norms were significantly less than the NCHA US data. Overall,
      respondents generally perceived the typical Canadian student to have used all 3
      substances. Perceived norms significantly predicted use, with students more
      likely to use alcohol, cigarettes, or marijuana if they perceived the typical
      student to use these substances. CONCLUSIONS: similar to their US peers, Canadian
      university students have inaccurate perceptions of peer substance use. These
      misperceptions may have potentially negative influences on actual substance use
      and could be a target for intervention. Further research examining the cross
      cultural differences for substance abuse is warranted.

PMID- 21186450
TI  - Engaging intercollegiate athletes in preventing and intervening in sexual and
      intimate partner violence.
AB  - OBJECTIVE: the object of this exploratory evaluation was to evaluate the
      "Bringing in the Bystander" sexual and intimate partner violence prevention
      program with a new sample of intercollegiate athletes. PARTICIPANTS AND METHODS:
      fifty-three male and female athletes participated in the program (experimental
      group), and 86 were in the control group. All completed pretest, posttest, and 2
      month follow-up surveys, including assessment of rape myth acceptance, intent to
      engage in bystander behaviors, bystander confidence, and bystander behaviors.
      RESULTS: the program worked overall and for both women and men, improved
      bystander confidence and intent to engage in bystander behaviors, and did not
      create significant backlash effects (ie, worsening of attitudes as a result of
      program). CONCLUSIONS: the program fits with the intent of the National
      Collegiate Athletic Association CHAMPS/Life Skills program regarding its focus on
      the overall development of student-athletes and demonstrates the promising
      bystander approach compatible with the 2007 American College Health Association
      toolkit, Shifting the Paradigm: Primary Prevention of Sexual Violence.

PMID- 21186451
TI  - Obesity and Food Choices Among Faculty and Staff at a Large Urban University.
AB  - OBJECTIVE: in order to address increasing health care costs associated with
      obesity, this study sought to determine prevalence of overweight and obesity and
      examine eating behaviors, food choices, health beliefs, and attitudes of
      university employees. PARTICIPANTS AND METHODS: an online survey was distributed
      to > 3,800 faculty and staff at a large public metropolitan university in Winter
      2008. RESULTS: almost half (48%) of 806 respondents were classified as overweight
      or obese. Compared to those with normal weights, overweight and obese respondents
      consumed fewer fruits and vegetables (p < .05), were less confident in making
      healthful food choices (p < .001), and were more influenced by food choices
      available in on-campus dining facilities (p < .05). CONCLUSIONS: obesity among
      university employees warrants attention. Because these employees have less self
      efficacy and consume less healthful diets than their normal weight colleagues,
      universities need to improve on-campus access to healthful foods.

PMID- 21186452
TI  - Sexual decision making for the "better than average" college student.
AB  - OBJECTIVES: to examine the impact of downward social comparison and the "known
      partner is a safe partner" heuristic on college students' sexual decisions.
      PARTICIPANTS: One hundred-eighty heterosexual or bisexual undergraduate college
      students. METHODS: participants read dating vignettes that varied on perspective
      and familiarity and then rated the likelihood the couple would engage in sexual
      intercourse and use a condom. RESULTS: there were no differences in rated
      likelihood based on familiarity, suggesting that the students did not view the 2
      partner types as significantly different. Students rated the likelihood of sexual
      intercourse lower and condom use higher when the vignette was presented from the
      second person perspective. CONCLUSIONS: the students' use of downward social
      comparison is consistent with the "better than average effect," suggesting that
      the students perceive their own behavior as safe. The implication is that safer
      sex messages might be most effective if they focus on what students will gain by
      practicing safer sex behaviors, not just avoidance of a risk behavior.

PMID- 21186453
TI  - Alcohol use in students seeking primary care treatment at university health
      services.
AB  - OBJECTIVE: given the high rate of at-risk drinking in college students, the
      authors examined drinking behaviors and associated factors in students being seen
      in student health services for primary care visits from October 30, 2004, to
      February 15, 2007. METHODS: analyses were based on a Health Screening Survey
      completed by 10,234 college students seeking general medical treatment. RESULTS:
      alcohol use was similar to other studies with 57% (n = 5,840) meeting the
      National Institute on Alcohol Abuse and Alcoholism criteria for at-risk drinking.
      Twenty-six percent of the students reported smoking at least once in the last 3
      months. Risk factors for at-risk drinking included young age, white males,
      drinking at a fraternity/sorority house, and use of tobacco. CONCLUSIONS: these
      findings support the widespread implementation of alcohol screening and
      intervention in university health services.

PMID- 21186454
TI  - Assessment of cardiovascular risk in collegiate football players and nonathletes.
AB  - Collegiate American football players may be at risk for cardiovascular disease.
      OBJECTIVE: to compare cardiovascular disease risk factors and cardiovascular
      structure and function parameters of football players, stratified by position, to
      a group of sedentary, nonathletes. PARTICIPANTS: twenty-six collegiate football
      players and 13 nonathletes participated in this study. METHODS: blood pressures,
      anthropometrics, and blood chemistries were obtained and analyzed using
      standardized procedures. Resting echocardiography was used to evaluate cardiac
      morphology and function. Brachial artery flow-mediated dilation was assessed
      using high-resolution ultrasonography. RESULTS: the prevalence of the metabolic
      syndrome was significantly higher amongst the linemen compared to the skill
      position players (46% versus 0%, p < .05). Mildly abnormal wall thickness was
      noted in 20% of the football players. No significant differences in vascular
      function were observed between the groups. CONCLUSIONS: the increased prevalence
      of the metabolic syndrome and its components in the collegiate linemen may
      increase cardiovascular disease risk.

PMID- 21186455
TI  - Do "clicker" educational sessions enhance the effectiveness of a social norms
      marketing campaign?
AB  - OBJECTIVE: social norms campaigns are a cost-effective way to reduce high-risk
      drinking on college campuses. This study compares effectiveness of a "standard"
      social norms media (SNM) campaign for those with and without exposure to
      additional educational sessions using audience response technology ("clickers").
      METHODS: American College Health Association's National College Health Assessment
      questions are used to evaluate actual and perceived use. Additional survey
      questions assess individual exposure to the interventions. RESULTS: the authors
      find "clicker" technology to be more effective than social norms poster media
      alone in reducing misperceptions of normative alcohol use for those students who
      attended clicker sessions. CONCLUSION: poster SNM campaigns may be most effective
      when supported by group "clicker" heath-related sessions.

PMID- 21186456
TI  - Changing the culture of alcohol abuse on campus: lessons learned from secondhand
      smoke.
AB  - Alcohol abuse is the single greatest public health hazard on American college and
      university campuses, but the culture of abusive alcohol consumption continues to
      be highly resistant to change. The author argues that secondhand smoke campaigns
      can be used as models to change the culture of alcohol abuse on campus. He
      proposes the implementation of "secondhand alcohol" campaigns and describes their
      essential components and advantages.

PMID- 21186458
TI  - Human motor transfer is determined by the scaling of size and accuracy of
      movement.
AB  - A transfer of training design was used to examine the role of the Index of
      Difficulty (ID) on transfer of learning in a sequential Fitts's law task.
      Specifically, the role of the ratio between the accuracy and size of movement
      (ID) in transfer was examined. Transfer of skilled movement is better when both
      the size and accuracy of movement are changed by the same factor (ID is constant)
      than when only size or accuracy is changed. The authors infer that the size
      accuracy ratio is capturing the control strategies employed during practice and
      thus promotes efficient transfer. Furthermore, efficient transfer is not
      dependent on maintaining relative timing invariance and thus the authors provide
      further evidence that relative timing is not an essential feature of movement
      control.

PMID- 21186459
TI  - An implicit basis for the retention benefits of random practice.
AB  - The cognitive effort explanations of contextual interference (CI) and implicit
      motor learning represent a paradox in which cognitive involvement is seen to be
      advantageous or disadvantageous for learning. The authors aimed to resolve this
      paradox by measuring cognitive effort and working memory dependence during low
      and high CI practice on two Australian Rules Football tasks (kicking and
      handball). Measures of cognitive effort included: kicking and handball outcome
      performance during acquisition and during a test of retention, performance on a
      probe reaction time task during a sample of acquisition trials, and self-reported
      levels of cognitive effort. Measures of implicit and explicit learning included
      kicking and handball performance during a secondary task transfer, and self
      report verbal protocols (number of verbal rules and hypotheses reported). The
      results suggest that high CI may cause an implicit mode of learning, perhaps due
      to the interference caused by task switching. However, these findings are
      restricted to the more complex of the 2 tasks (kicking).

PMID- 21186460
TI  - Development of an evaluation scale for sitting and standing from the ground for
      children with Duchenne muscular dystrophy.
AB  - The authors developed an evaluation scale for sit-stand from the ground for
      children with Duchenne muscular dystrophy (DMD) and tested its reliability. The
      construction occurred in stages: (a) the characterization of the movement in
      healthy children, (b) the characterization of the movement in children with DMD,
      (c) the elaboration of the 1st version of the scale and the manual, (d) the
      evaluation by experts and readjustments, and (e) the analysis of inter- and
      intraexaminer reliability and correlation with the Vignos Scale, age, and time
      for the execution of the activity. The scale comprehended 3 phases for sitting
      and 5 for the standing. A very good repeatability of the measures of sitting and
      standing (ICC = 0.89 and 0.84, respectively) and excellent reproducibility (ICC =
      0.93 and 0.92, respectively) was demonstrated. The Kappa coefficient for the 8
      phases in the interexaminer analysis varied from 0.77 to 1.00 (excellent
      reliability), and in the intraexaminer analysis varied from 0.80 to 1.00
      (excellent reliability). Good correlation was found between the variables on the
      Vignos Scale (age: r = 0.58; stand: r = 0.56). The scale is a reliability
      instrument that allows evaluation of the activity of sitting and standing in
      children with DMD.

PMID- 21186461
TI  - Time to task failure of trunk extensor muscles differs with load type.
AB  - Time to task failure of trunk extensor muscles during seated submaximal isometric
      exertions was assessed in 18 healthy participants using 2 different load types.
      One required supporting an inertial load (position-matching task) whereas the 2nd
      required maintaining an equivalent torque against a rigid restraint (force
      matching task). Time to task failure was significantly longer for position
      matching tasks compared to the force-matching tasks. This finding is opposite to
      that reported for the appendicular muscles. A subset of 4 individuals completed a
      2nd experiment to test the time to task failure of the elbow flexors in the
      position- and force-matching tasks. Time to task failure of the elbow flexors was
      significantly longer for the force-matching tasks compared to position matching.
      Thus, the same population shows that the effects of load type on time to task
      failure are opposite for the appendicular and axial muscles. This could be an
      important issue in understanding the mechanisms of task failure, and the
      endurance capacity of the trunk extensor muscles.

PMID- 21186463
TI  - Motor imagery may incorporate trial-to-trial error.
AB  - The authors tested for 1/f noise in motor imagery (MI). Participants pointed and
      imagined pointing to a single target (Experiment 1), to targets of varied size
      (Experiment 2), and switched between pointing and grasping (Experiment 3).
      Experiment 1 showed comparable patterns of serial correlation in actual and
      imagined movement. Experiment 2 suggested increased correlation for MI and
      performance with increased task difficulty, perhaps reflecting adaptation to a
      more complex environment. Experiment 3 suggested a parallel decrease in
      correlation with task switching, perhaps reflecting discontinuity of mental set.
      Although present results do not conclusively reveal 1/f fluctuation, the emergent
      patterns suggest that MI could incorporate trial-to-trial error across a range of
      constraints.

PMID- 21186464
TI  - Ich denk' es war ein gutes Jahr* (Reinhard Mey, 1968)--the year 2010 balance.

PMID- 21186465
TI  - Preoperative candidate evaluations for retinal  prosthesis trials.
AB  - With the development of retinal prostheses, the first clinical trials for these
      devices are being planned or are already underway. Yet the candidate selection
      criteria and the preparation of early recipients have received very little
      attention. As clinical trials grow in scope, the need for such issues will become
      increasingly important. Especially in preliminary stages of clinical trials, it
      is absolutely vital to develop the preoperative evaluations of candidates in
      identifying the suitable candidate for retinal prosthesis implants. This paper
      addresses the preoperative evaluations of candidates that may provide insight
      into selecting potential candidates for retinal prosthetic devices. Screening an
      ideal candidate is complex and, at the minimum, should include medical
      evaluations, visual function tests, assessments of psychological status,
      motivation, expectations, as well as rehabilitation capabilities. This will
      ensure that appropriate candidates are selected, candidate expectations are
      managed, and success with the retinal prosthetic devices is maximized.

PMID- 21186466
TI  - Left ventricular assist improves autonomic imbalance in patients with persistent
      myocardial dysfunction.
AB  - BACKGROUND: Left ventricular assist devices (LVAD) are an effective therapeutic
      option for end-stage heart failure (HF). Reduced heart rate variability (HRV) as
      a result of autonomic derangement is evident in chronic heart failure and several
      studies have established the independent prognostic value of HRV in chronic heart
      failure. OBJECTIVE: In the present study we investigated whether autonomic
      function is restored in patients after LVAD implantation with persistent,
      severely depressed left ventricular function. METHODS: Ambulatory Holter ECG
      recordings were collected in heart failure patients with an LVAD (n=8) und age
      matched heart failure patients without an LVAD (n=7) both on optimal medical
      therapy. Cardiac dimensions and function were assessed by echocardiography or
      angiography. RESULTS: Analysis for heart rate variability revealed reduced SDNN
      (67+/-4 ms), SDANN (56+/-4 ms) and triangular index (18+/-1) in heart failure
      patients on optimal medical therapy. However patients with LVAD demonstrated a
      restoration in heart rate variability with normal SDNN (108+/-9 ms), SDANN (103+/
      8 ms) and triangular index (29+/-2). Compared to patients without LVAD this
      difference was statistically significant (p<0.01). CONCLUSIONS: In end-stage
      heart failure patients autonomic imbalance indicated by severely reduced heart
      rate variability is restored after LVAD implantation with unloading of the
      failing heart.

PMID- 21186467
TI  - Numerical simulation and experimental validation of swirling flow in spiral
      vortex ventricular assist device.
AB  - Spiral vortex ventricular assist device (SV-VAD) supports cardiac patients with
      refractory heart failure. Unfortunately, thrombus formation and risk of stroke
      due to flow complications may lead to aggravated conditions. The hemodynamics of
      a continuous flow in the ventricular chamber of a SV-VAD can be analyzed using
      numerical simulation. Particle image velocimetry and laser Doppler anemometry are
      utilized for validating the simulated spiral flow in a transparent acrylic SV-VAD
      replica based on its cross-sectional averaged axial and tangential velocities.
      After validation, the relationship between swirling flow and blood cell damage is
      established by evaluating flow effect on thrombosis due to high shear stress.
      Based on our analysis, stagnancy of the flow within the SV-VAD is insignificant
      and its low shear stress minimizes hemolysis.

PMID- 21186468
TI  - Beat-rate dependent mitral flow patterns for in vitro  hemodynamic applications.
AB  - The conservative surgery approach for restoring the functionality of heart valves
      has predominated during the last two decades, particularly for the mitral valve.
      In vitro pulsatile testing is a key methodology for the investigation of heart
      valve hemodynamics, and particularly for the ideation, validation and
      optimization of novel techniques in heart valve surgery. Traditionally, however,
      pulsatile mock loops have been developed for the study of aortic valve
      substitutes, and scarce attention has been paid in replicating the mitral flow
      patterns with due hemodynamic fidelity. In this work we provide detailed
      analytical expressions to produce beat-rate dependent, physiologic-like mitral
      flow patterns for in vitro applications. The approach we propose is based on a
      biomechanical analysis of the factors which govern hemodynamic changes in the
      mitral flow pattern, namely in terms of E and A wave contours and E/A peaks
      ratio, when switching from rest to mild exercise conditions. The patterns from
      the model we obtained were in good agreement with clinical literature data in
      terms of i) gradual superimposition of the E and A wave, which yielded a single
      peak at 96 bpm; ii) decrease in the E/A ratio with increasing heart rate; iii)
      amount of flow delivered by each of the two waves. The proposed method provides a
      physiologically representative, beat-rate dependent analytical expression of the
      mitral flow pattern, which can be used in in vitro hydrodynamic investigations to
      accurately replicate the changes that the flow waves experience when the heart
      rate shifts from rest to mild exercise conditions.

PMID- 21186469
TI  - Accelerated angiogenic induction and vascular  integration in a novel synthetic
      scaffolding matrix for  tissue replacement.
AB  - PURPOSE: Reduced or delayed neovascularization is a major obstacle with regard to
      tissue-engineered constructs. The aim of this study was to evaluate the early
      microvascular response to a novel degradable epsilon-caprolactone terpolymer
      matrix. METHODS: epsilon-caprolactone terpolymer matrices (Suprathel Plus(r);
      Institute of Textile and Process Engineering, Denkendorf, Germany) were implanted
      into dorsal skinfold chambers of balb/c mice (n=10). Microcirculatory changes
      were observed by intravital fluorescence microscopy. Scaffolding matrices from
      PEGT/PBT copolymer were used as controls (n=10). RESULTS: The formation of de
      novo vascular networks within both scaffolding matrices was noted throughout the
      experiment. A vascular ingrowth of perfused microvessels into the matrices up to
      600 MUm apart from the edge was noted within 10 days of implantation. The
      earliest signs of neoangiogenesis were visible in epsilon-caprolactone terpolymer
      matrices on day 1. In both scaffolds the new developed vessels extended
      centripetally from the border of the matrices towards the center and anastomosed
      to form a perfused microvascular network. There was significantly earlier onset
      of vascularization, increased vascularized area and higher vessel density in
      epsilon-caprolactone terpolymer matrices compared to PEGT/PBT copolymer matrices
      were observed. CONCLUSIONS: The scaffolding matrix from epsilon-caprolactone
      terpolymer allowed for an earlier and more intense induction of angiogenesis and
      displayed the tendency to vascularize more rapidly within a shorter period of
      time after transplantation compared to PEGT/PBT copolymer scaffolds, thus
      indicating its potential application for tissue engineering purposes.

PMID- 21186470
TI  - Three-dimensional microfabricated scaffolds with  cardiac extracellular matrix
      like architecture.
AB  - In recent years, research in the field of myocardial tissue engineering has
      advanced thanks to the development of new biomaterials and a more clear
      understanding of processes that are at the basis of cardiac tissue growth.
      However, classical porous scaffolds developed during these years to try to
      reconstruct and mimic heart function have proven to be inadequate because they
      are not able to reproduce the typical myocardial environment. One approach to
      increase functionality of tissue-engineered constructs relies on attempts to
      mimic the microarchitecture of natural tissues, since it is well known that
      topology is one of the principal stimuli that cells need to activate their
      functions. The aim of this work was the realization of three-dimensional
      microfabricated scaffolds, with cardiac extracellular matrix (ECM)-like
      architecture. For this purpose, samples of pig myocardium were decellularized,
      embedded in paraffin wax and analyzed under an optical microscope, in order to
      evaluate the geometrical features of the cardiac ECM. On the basis of these data,
      a simplified model of the cardiac ECM microarchitecture was designed.
      Microfabricated scaffolds were realized with Soft Lithography technique, using a
      bioartificial blend, based on alginate, gelatin and a novel poly(N
      isopropylacrylamide)-based copolymer, which we synthesized. The scaffolds were
      characterized in terms of topological and mechanical properties. Moreover, cell
      adhesion, proliferation, and differentiation tests were performed. The
      microfabricated scaffolds showed they matched the anisotropic mechanical
      properties of adult human left ventricular myocardium, while at the same time
      being able to promote myoblast alignment in the absence of external stimuli.

PMID- 21186471
TI  - In vitro evaluation of hydraulic characteristics of  prototype implantable
      intrathecal infusion pump.
AB  - The use of the intrathecal infusion pump for therapeutic treatment and pain
      management is increasing. For example, one such application is the pain treatment
      of cancer patients suffering from severe chronic pain, where all other treatment
      methods have failed. This method is gaining popularity because of its high cure
      effect with low dosage. In this study, we developed a prototype implantable
      intrathecal infusion pump and evaluated its mechanical and hydraulic
      characteristics in vitro to determine how its performance varied under different
      environmental conditions. The data are reported as means (standard deviations).
      In the experiments, the prototype pump could control the micro-scale infusion
      amount, and its performance was affected by ambient temperature and pressure
      conditions. In a temperature change test, at a constant pressure of 1.0 atm, the
      minimal amounts of a bolus were 4.44 (1.07), 5.06 (1.17), and 5.54 (0.90) uL for
      the temperature of 27.5, 36.5, and 42 degrees C, respectively. In a pressure
      change test, at a constant temperature of 36.5 degrees C, the minimal amounts of
      a bolus were 5.06 (1.17), 5.94 (0.67), and 6.13 (0.39) uL for pressures of 1.0,
      0.9 and 0.8 atm, respectively. These experimental results demonstrate the
      possibility of using the prototype pump as an implantable microvolumetric
      infusion device. However, this prototype pump will have to undergo further design
      enhancement before being clinically feasible for such an application.

PMID- 21186472
TI  - Changes in red blood cell size and red cell  fragmentation during hemodialysis.
AB  - INTRODUCTION: Intradialytic hypotension remains the commonest complication for
      outpatient hemodialysis. The majority of relative blood volume (RBV) monitoring
      techniques monitor changes in hematocrit. As hematocrit can potentially be
      affected by changes in red cell size and hemolysis we studied the change in red
      blood cell size (MCV) during dialysis and hemolysis. METHODS: MCV was
      prospectively measured in 176 stable regular adult hemodialysis outpatients (56%
      male, 27.8% diabetic, mean age 59.5 +/-16.2 years) dialyzing against a range of
      dialysate sodiums (136-145 mmol/L), with cooled dialysate (35-36 degrees C),
      containing 1 g/L glucose, with constant ultrafiltration profiles. Red cell
      fragmentation was studied in 41 of the cohort. RESULTS: Logistical regression
      analysis showed that the absolute change in MCV was related to the change in
      hematocrit (F=4.92, beta=0.111, p=0.031), and inversely with red cell shrinkage
      associated with predialysis osmolality (F=5.06, beta=0.83, p=0.029), and
      dialysate sodium (F=4.7, beta=0.34, p=0.035). There was no significant increase
      in red cell fragments during the dialysis sessions. CONCLUSIONS: Indirect
      assessment of RBV based upon the relative change in hematocrit, depends not only
      upon the change in plasma water and red blood cell numbers, but also upon MCV.
      Changes in MCV may theoretically lead to potential effects on RBV measurements.

PMID- 21186480
TI  - [The advantages and disadvantages of GMS and PAS Staining in fungal keratitis].
AB  - PURPOSE: To compare the advantages and disadvantages of GMS and PAS Staining in
      the diagnosis of fungal keratitis. METHODS: Retrospectively analysed the sections
      of 102 cases of fungal keratitis from November 2007 to June 2010 in our
      department. Statistically analysed the positive rate of different statining
      methods, and summarized technical cruxes of GMS and PAS staining. RESULTS: The
      positive rates of GMS and PAS staining for fungal keratitis were 100% and 93.14%,
      respectively. CONCLUSION: GMS staining is better than PAS staining for fungal
      keratitis in displaying fungi. And it takes less time, is easier to operate and
      presents a more durable colour compared with PAS staining. But PAS staining is
      superior to GMS staining in displaying fungal septa and eliminating interference
      from pigment-containing cells and other cells.

PMID- 21186481
TI  - [Clinical study of the effect of amnion membrane transplantation on diminishing
      corneal neovascularization induced by alkali burn].
AB  - PURPOSE: To study the curative effect of amnion membrane transplantation on
      decreasing corneal neovascularization(CNV) induced by alkali burn. METHODS: It
      was a non-randomized retrospective case-control study. Among 19 cases (23 eyes)
      of third-degree alkali burns from 2006 to 2010, 11 cases (13 eyes) were performed
      with amnion membrane transplantation operation, and others were not. Amnion
      membrane transplantation was performed at 3rd day after burns in the treatment
      group. Ages and treatments beyond surgery of double groups were matched. Areas of
      CNV in double groups were measured at the 14th and 60th days after burn.
      RESULTS:Area of CNV in the treatment group was (62.133+/-8.571) mm2 at the 14th
      day after burn, and was 30.6% lower than that in the control group. Area of CNV
      in the treatment group was (112.019+/-17.362)mm2 at the 14th day after burn, and
      was 13.5% lower than that in the control group. There was statistical
      significance between the two groups (P<0.05). CONCLUSION: Amnion membrane
      transplantation operation can inhibit the growth of corneal neovascularization
      induced by alkali burn.

PMID- 21186482
TI  - [Retinal symmetry of multifocal visual evoked potential in both eyes of normal
      subjects].
AB  - PURPOSE: To analyze the retinal symmetry of multifocal visual evoked potential
      (mfVEP) in both eyes of normal subjects. METHODS: The monocular mfVEP in both
      eyes of 36 normal subjects (72 eyes) were tested with VERIS Science 4.0. The
      stimulus was the pattern reversal dart array consisted of 60 sectors, each
      included 16 black-white reverse patterns. The visual stimulation was controlled
      by a binary pseudo-random m-sequence and subtended 25 degrees of retinal region.
      RESULTS: The mfVEP patterns between left and right eyes of each subject were
      similar, and P1 latency and amplitude in correspondent visual field quadrants
      between left and right eyes had no significant difference(P>0.05). The latency of
      superotemporal visual field quadrant in right eyes was shorter than that of
      superonasal visual field quadrant in left eyes, and the amplitude of superonasal
      visual field quadrant in right eyes was longer than that of superotemporal visual
      field quadrant in left eyes(P<0.05). The P1 latency and amplitude among four
      visual field quadrants of each eye had significant difference(P<0.05). The P1
      latency between the superonasal visual field quadrant and inferotemporal visual
      field quadrant or between the superonasal visual field quadrant and inferonasal
      quadrant visual field had significant differences in right or left eyes(P<0.05).
      CONCLUSION: The mfVEP of normal subjects exists retinal symmetry.

PMID- 21186483
TI  - [Target Z-axis optimized LASIK for 2 cases with decentered ablation].
AB  - PURPOSE: To report target z-axis optimized LASIK treating for two eyes from two
      patients with decentered ablation. METHODS: The LaserSight AstraPro2.2 Z software
      is a topography-guided custom ellipsoid ablation platform. LASIK with target z
      axis optimization was performed to restore pre-operative visual axis using a
      LaserSight SLX excimer laser (version 5.3,300Hz). RESULTS: During preoperative
      examination, the uncorrected visual acuity (UCVA) was 0.5 in both eyes, and the
      best spectacle-corrected visual acuities(BSCVA) were 1.0 and 0.8. The decentered
      ablation zones were diagnosed with LaserSight AstraMax topography. Following
      target z-axis microtranslation, fifteen and eight MUm of central corneal tissues
      were preserved in the two eyes, respectively. The UCVA was 1.2 in both eyes, and
      secondary ablation zones were both centered on the visual axis. Topography maps
      and UCVA were stable in both eyes at the time of final follow-up. CONCLUSION:
      Using target z-axis optimized LASIK with the LaserSight AstraPro Planner 2.2 Z
      customized ablation software was an effective method to modify decentered
      ablation and restore the visual axis.

PMID- 21186484
TI  - [Image characters of optical coherence tomography in laser-induced maculopathy].
AB  - PURPOSE: To observe the changes of ocular fundus and to describe the image
      features of optical coherence tomography (OCT) in patients with laser-induced
      maculopathy. METHODS: Four patients (4 eyes) with decreased visual acuity due to
      laser injury were recruited into the study between April 2002 to December 2009.
      All patients underwent routine check-up for eyes. RESULTS: The four cases
      presented with different clinical characteristics from each another. In the first
      case, OCT showed lamella macular hole, with partially remained outer sensory
      retina. The signals of inner segments/outer segments (IS/OS) band and RPE band
      were disrupted. The choroidal band was distorted with increased reflection.
      Perimacular epiretinal membrane and vitreous hemorrhage were also observed. The
      second case had a full-thickness macular hole with retina edema surrounding the
      hole. The third case presented local serous sensory retinal detachment in macula.
      The fourth case presented hyper-reflection of the inner retina in macula which
      indicated hemorrhage. CONCLUSION: There are various patterns of laser-induced
      maculopathy. OCT is a useful noninvasive diagnostic tool to delineate the layer,
      extent and configuration of the damage on retina.

PMID- 21186485
TI  - [The clinical analysis of shallow anterior chamber after complex trabeculectomy
      surgery].
AB  - PURPOSE: To investigate the clinical cause, therapy and prognosis of shallow
      anterior chamber after complex trabeculectomy surgery of glaucoma. METHODS: A
      retrospective study of 267 patients (302 eyes) diagnosed with glaucoma at our
      hospital were reviewed. RESULTS: Forty-three among 302 eyes presented shallow
      anterior chamber(14.24%).The main causes of shallow anterior chamber after
      surgery included excessive filtering function, conjunctival exudation, choroidal
      detachment and ciliary circle block. These patients recovered after receiving
      conservative or surgical treatment. CONCLUSION: The shallow anterior chamber is a
      complication frequently occurring following complex trabeculectomy surgery. The
      occurrence of this complication may be decreased by controlling filterableness
      and moderately applying mitomycin C intraoperatively; The prognosis may be
      significantly enhanced by detecting main measurements including anterior chamber,
      intraocular tension, filtration condition,and by interfering in shallow anterior
      chamber early after complex trabeculectomy surgery.

PMID- 21186486
TI  - [Study of the reliability in one dimensional size measurement with digital slit
      lamp microscope].
AB  - PURPOSE: To study the reliability of digital slit lamp microscope as a tool for
      quantitative analysis in one dimensional size measurement. METHODS: Three single
      blinded observers acquired and repeatedly measured the images with a size of 4.00
      mm and 10.00 mm on the vernier caliper, which simulatated the human eye pupil and
      cornea diameter under China-made digital slit lamp microscope in the objective
      magnification of 4 times, 10 times, 16 times, 25 times, 40 times and 4 times, 10
      times, 16 times, respectively. The correctness and precision of measurement were
      compared. RESULTS: The images with 4 mm size were measured by three investigators
      and the average values were located between 3.98 to 4.06. For the images with
      10.00 mm size, the average values fell within 10.00 ~ 10.04. Measurement results
      of 4.00 mm images showed, except A4, B25, C16 and C25, significant difference was
      noted between the measured value and the true value. Regarding measurement
      results of 10.00 mm iamges indicated, except A10, statistical significance was
      found between the measured value and the true value. In terms of comparing the
      results of the same size measured at different magnifications by the same
      investigator, except for investigators A's measurements of 10.00 mm dimension,
      the measurement results by all the remaining investigators presented statistical
      significance at different magnifications. Compared measurements of the same size
      with different magnifications, measurements of 4.00 mm in 4-fold magnification
      had no significant difference among the investigators', the remaining results
      were statistically significant. The coefficient of variation of all measurement
      results were less than 5%; as magnification increased, the coefficient of
      variation decreased. CONCLUSION: The measurement of digital slit lamp microscope
      in one-dimensional size has good reliability,and should be performed for
      reliability analysis before used for quantitative analysis to reduce systematic
      errors.

PMID- 21186487
TI  - [Refractive error's distribution and clinical characteristics of preterm and full
      term children].
AB  - PURPOSE: To observe the abnormal refractive state and clinical characteristics in
      preterm and full-term children in the department of pediatric ophthalmology.
      METHODS: The ocular refraction status of 358 eyes in 51 preterm and 128 full-term
      children were checked by retinoscopy in dilated pupil after being used atropine
      eye drop. RESULTS: There were 157 eyes with hyperopia accounting for 61.3% in
      preterm children, 25 eyes with hyperopia accounting for 24.5% in full-term
      children. The main type of refractive errors in preterm children was astigmatism,
      especially high-astigmatism, mixed astigmatism. And the morbidity of astigmatism,
      hyper-astigmatism, mixed astigmatism in preterm children was higher than those in
      full-term children. CONCLUSION: Astigmatism, especially high astigmatism and
      complex mixed astigmatism are important reasons for low vision in preterm
      children. Clinically, there is close relationship between astigmatism and
      amblyopia. So it can not be ignored with preterm children's visual development,
      and refractive screening could be bring forward to two years old.

PMID- 21186488
TI  - [The reading speed of adolescent with low vision used electronic visual aids].
AB  - PURPOSE: To evaluate the reading speed of adolescents with different causes of
      low vision using electronic visual aids. METHODS: The screening of 10 young
      students from Quanzhou Blind School could read Chinese N5 print by different
      optical aids. After their refractive correction and ophthalmic examination, the
      reading speeds with Chinese N5 print were measured using various optical and
      electronic visual aids. RESULTS: The reading speed of (34.36+/-5.06) word / min
      by electronic visual aids performed faster than that of (18.50+/-6.54) word / min
      by optical visual aids in 10 young students with low vision (P<0.05). The reading
      speed of young people with low vision due to different causes had no direct
      linear correlation with their near visual acuity(P>0.05). CONCLUSION: The
      electronic visual aids more significantly improve the reading speed of young
      people with low vision than the optical visual aids did. The reading speed of
      young people with low vision is not relevant to their near visual acuity induced
      by different causes.

PMID- 21186489
TI  - [An improved method of culturing human umbilical vein endothelial cells and its
      characterization].
AB  - PURPOSE: To establish a simple and convenient method for the culture of human
      umbilical vein endothelial cells (HUVECs) and study its characterization in
      vitro. METHODS: Human Umbilical cord was isolated and digested by collagenase
      type I,and then it was cultured in 1.5% geltain coated dish with 10% fetal bovine
      serum(FBS),heparin sodium andbeta-endothelial cell growth factor(beta-ECGF) in
      human endothelial basal growth medium.HUVECs were identified by anti-human factor
      VIII related antigen and CD31 immunohistochemical staining. RESULTS: We could
      successfully culture HUVECs by using this method. HUVECs attached the dish in 24
      hours and the confluence was seen in 5 days. HUVECs were generally positive for
      anti-human factor VIII related antigen and CD31. CONCLUSION: It is a fast and
      effective method to successfully culture purified HUVECs in which collagenase
      type I was used to digest HUVECs with glass tube connected to T-tube, human
      endothelial basal growth medium containing 10% FBS,heparin sodium and beta-ECGF
      in 1.5% geltain coated dish.

PMID- 21186490
TI  - [The photopic electroretinogram in normal adult sd rat].
AB  - PURPOSE: To study the characteristics of photopic flash electroretinogram (ERG)
      in normal adult SD rats. METHODS: Sixty normal adult SD rats aged 9 to 12 weeks
      were enrolled in this study. Photopic flash ERG were recorded from these 60 SD
      rats. The results were statistically analyzed with SPSS software. RESULTS: Stable
      a, b and PhNR wave could be recorded in each rat. Implicit time of a wave,
      implicit time and amplitude of PhNR fit normal distribution. Implicit time of
      PhNR was (124.6+/-8.5) ms with the smallest coefficient of variation of 0.07. The
      amplitude of PhNR was (11.3+/-4.2) MUV and coefficient of variation was 0.37.
      There was no difference in the results between female and male rats. CONCLUSION:
      Photopic flash ERG is an objective method in evaluating the retinal function in
      SD rats and PhNR can be used as a sensitive index of inner retinal function.

PMID- 21186491
TI  - [Inhibitory effect of diclofenac sodium on the proliferation of rabbit corneal
      epithelial cells in vitro].
AB  - PURPOSE: To investigate the inhibitory effect of diclofenac sodium on rabbit
      corneal epithelial cells (RCECs) in vitro and explore its pharmacological
      mechanism. METHODS: The fresh rabbit cornea was cultured to obtain the primary
      RCECs, and RCECs of passage 2 were used in this research. The cells were divided
      into experimental groups, the cells in which were incubated with different
      concentrations (18.18, 27.27, 36.36, 45.45, 54.55 MUg/ml) of diclofenac sodium,
      and control group. The effect of diclofenac sodium on the proliferation of cells
      was measured by methyl thiazolyl thiazolium (MTT) assay 24, 48 and 72 h after
      incubation. While the RCECs were divided into experimental groups, the cells in
      which were incubated with 9 and 12.5 MUg/ml diclofenac sodium, and control group.
      The cell cycle and apoptotic rate were observed by flow cytometer. RESULTS: MTT
      assay showed that diclofenac sodium had obvious inhibitory effect on RCECs, and
      the inhibition rate was increasing along with the increasing concentration of
      diclofenac sodium and the incubation time(P<0.05). Flow cytometer showed that
      after incubation with diclofenac sodium, the cells in G0/G1 phase were obviously
      increased, and the apoptosis cusp and apoptotic rate were increased. CONCLUSION:
      Diclofenac sodium exerts significant inhibitory effect on RCECs in a dosage
      dependent manner, and it may function by inducing cell apoptosis and ceasing cell
      cycles.

PMID- 21186492
TI  - [An in vivo study of basic fibroblast growth factor on activation and
      proliferation of retinal progenitor cell in RCS rats].
AB  - PURPOSE: To investigate the effect of intravitreal basic fibroblast growth
      factor(bFGF) on activation and proliferation of endogenous retinal progenitor
      cells in the Royal College of Surgeons(RCS) rats. METHODS: Twenty-four rats were
      studied after the 30th postnatal day(>=30). Eighteen affected rats were randomly
      divided into 3 groups: bFGF-treated, vehicle-treated and untreated group, and 6
      unaffected rats were used as normal controls. Six MUl of bFGF (5MUg/10 MUl) or
      vehicle was injected into the vitreous on days 31, 33 and 35 after birth (P31,
      P33, P35) in the bFGF group and vehicle group, and no injection was administered
      in the untreated and control groups. All the rats were euthanized, and their eyes
      were enucleated, hemisected and fixed at 50 d after birth for
      immunohistochemistry and measurement of outer nuclear layer thickness. RESULTS:
      Nestin and Chx10 were positively expressed in all retinal layers, intravitreous
      injection of bFGF in retina-dystrophic RCS(RCS-p+/Lav) rats induced intense
      labeling for the retinal progenitor cell markers Chx10 and Nestin, which were
      highly colocalized. Fluorescence intensity for both labels was slightly less in
      the control rats, and much less in the vehicle-injected rats as well as in the
      untreated RCS rats. The outer nuclear layer (ONL) was significantly thicker in
      bFGF group than that of vehicle-treated or untreated group(p<0.01), but thinner
      than that of the control group(p<0.01). No significant difference was observed in
      the ONL thicknesses between the vehicle group and untreated group(P>0.05).
      CONCLUSION: bFGF may contribute to the activation of retinal progenitor cells in
      RCS rats, thus counteract degeneration by promoting the proliferation of the
      progenitor cells.

PMID- 21186494
TI  - [anastomosis lacrimal sac conjunctival sac in severe laceration of lacrimal
      canaliculus].
AB  - PURPOSE: To investigate the clinical effect of anastomosis lacrimal sac
      conjunctival sac in the treatment of severe laceration of lacrimal canaliculus.
      METHODS: A total of 19 cases (19 eyes) with laceration of lacrimal canaliculus
      underwent anastomosis lacrimal sac conjunctival sac.All the patients were
      followed up for 3 to 24 months postoperatively. RESULTS: Among all the 19
      patients (19 eyes), 14 cases were cured,3 cases wre markedly improved and 2 cases
      had no effect,and the effect rate was 89.47%. CONCLUSION: Anastomosis lacrimal
      sac conjunctival sac is an effective surgical technique in the management of
      severe laceration of lacrimal canaliculus.

PMID- 21186493
TI  - [Ultrastructural changes of the trabecular meshwork in glucocorticoid induced
      glaucoma].
AB  - PURPOSE: Steroid-induced glaucoma in rabbit ocular was established to observe the
      ultrastructural changes in trabecular meshwork,and to preliminarily study the
      mechanisms of increased resistance of aqueous outflow in steroid-induced
      glaucoma. METHODS: Forty New Zealand white rabbits were randomly divided into
      four groups, namely,control group (n = 10 rats),drops drug group(n = 10 rats),
      Injecting drug group(n = 10 rats) and drug combination group (n=10 rats). For
      three consecutive days before the experiment,using the Schitoz's tonometer to
      measure intraocular pressure(IOP) at 8am, 10am, and 12am each day,obtained the
      average,and finally calculated basis IOP of these rabbits. The rabbits eyes in
      drug combination group of were treated with dexamethasone sodium phosphate
      solution (0.5%)for 8 weeks,three times a day, and given injection of
      triamcinolone endure (3 mg) weekly. While the rabbits eyes in the control group
      were treated with sterile saline in the same period of experiment.After 4
      days,IOP of the rabbit was measured by Schitoz's tonometer weekly( the IOP was
      measured at 8am, 10am, 12am each day for the average value).The rabbit whose IOP
      was more than 21.97 mmHg and continued for one week is regarded a successful
      animal model as Corticosteroid. After 8 weeks,the eyes of control group and
      Corticosteroid rabbits was made for Transmission electron microscopy(TEM)
      specimen which was used to study the ultrastructural of trabecular meshwork cell.
      RESULTS: 1.The Rabbit-based IOP was (18.082+/-2.398) mmHg(n=80),in the drug
      combination group The IOP of rabbit is up to (24.056+/-1.245) mmHg after three
      weeks,which was significantly higher compared with that of(18.254 +/- 3.465) mmHg
      in the control group,the difference had significance(p<0.05),after six weeks,
      which reached the peak, up to (30.214+/-0.766) mmHg,in the eighth week, up to
      (29.144+/-0.685) mmHg, the IOP of 16 rabbit eyes from 20 rabbit eyes in the
      exprimental group increased.The positive rate was 80%.2. After treatment with
      dexamethasone,the abnormality of nucleus of the trabecular meshwork cell was
      increased, microfilament and microtubules among interstitial cells also increased
      ,cytoplasmic vacuolation, rough endoplasmic reticulum expansion, as well as an
      increase in intercellular amorphous material. CONCLUSION: 1.The glucocorticoid
      induced high intraocular pressure rabbit model has been successfully established
      in drug combination group.2.A series of changes in the cytoskeleton observed
      under the transmission electron microscopy are an important part of
      glucocorticoid-induced elevation of intraocular pressure.

PMID- 21186495
TI  - Deep brain stimulation shows promise for Alzheimer's, depression treatment.
      Doctors also now have more options in how DBS is used to treat Parkinson's
      disease.

PMID- 21186496
TI  - Gender-specific vs. standard implants.  Yet another study finds no need for
      gender-specific knee prostheses.

PMID- 21186497
TI  - High-tech oral cancer detection. Less invasive, less painful microchip technology
      could identify mouth cancers in the very early stages.

PMID- 21186498
TI  - How much is too much calcium? In supplement form, take it in combination with
      vitamin D, but try to get most of your calcium from foods you eat.

PMID- 21186499
TI  - MRSA infections decline, but new bacterial strains threaten.  You can take action
      to protect yourself against drug-resistant bacteria.

PMID- 21186500
TI  - Are there alternatives to total hip replacement? I am 70 years old, have
      osteoarthritis, and fear it is affecting my hip joint. I am otherwise in good
      health.

PMID- 21186501
TI  - [Cholera: always ready for].

PMID- 21186502
TI  - [Antimicrobial susceptibility, capsular serotypes and clonal relationship of
      invasive streptococcus pneumoniae isolates in adult population of the Bio-Bio
      region, Chile. 2005-2006].
AB  - Streptococcus pneumoniae infections constitute a public health problem. In our
      country there is scarce information regarding isolates from bacteraemic episodes
      in adult population. The antibiotic susceptibility, serotypes and clonal
      relationship of 56 isolates of S. pneumoniae from adult patients with bacteraemic
      infections in Concepcion-Talcahuano, Bio-Bio Region, Chile, were studied.
      Resistance to tetracycline (21.4%), trimethoprim/ sulfamethoxazole (18%),
      erythromycin (18%), chloramphenicol (7%) and 1 penicillin resistant isolate from
      a meningeal focus (2%) was found. Also, all the isolates were susceptible to
      cefotaxime, levofloxacin, moxifloxacin and vancomycin. A wide variety of capsular
      serotypes was demonstrated, with predominance of serotypes 1, 5, 23F, 7F and 3.
      The macrorestriction analysis by pulse field electrophoresis revealed 31
      electrophoretic patterns and 12 clonal groups, discarding a predominant clone.
      According to the results, at least, 80% of the S. pneumoniae serotypes isolated
      from bacteraemic adult patients are included in the available commercial vaccine.

PMID- 21186504
TI  - [Wise men in axial time].

PMID- 21186503
TI  - [Morphological findings in fatal cases of hantavirus cardiopulmonary syndrome.
      Report of 7 autopsies].
AB  - INTRODUCTION: Hantavirus cardiopulmonary syndrome (HCPS) is an acute infectious
      disease characterized by sudden cardiorespiratory failure and high mortality,
      caused by a RNA virus of the genus Hantavirus, family Bunyaviridae, 15% of
      Chilean cases have been detected in the Araucania Region. OBJECTIVE: To determine
      in fatal cases of HCPS, clinical and morphological characteristics. MATERIALS AND
      METHODS: Descriptive-retrospective analysis of seven fatal cases with postmortem
      study of HCPS, attended between 1997 and 2009 at the Hospital of Temuco, Chile.
      RESULTS: Cases were young patients from rural areas, and presented as an illness
      of progressive respiratory failure, with leukocytosis, thrombocytopenia and
      bilateral interstitial pulmonary infiltrates. Main morphological findings were
      marked intersticial and intraalveolar pulmonary edema, with minimal epithelial
      injury and mononuclear cell intersticial infiltrate and mild edematous
      intersticial inflamatory process. CONCLUSIONS: Epidemiological, clinical and
      laboratory background allow to suspect HCPS. In fatal cases, the autopsy makes
      possible to discard other similar pathologies and provide tissue for confirmation
      of the disease.

PMID- 21186505
TI  - [Strategies for dealing with cholera disease. A public health perspective of the
      Chilean experience].
AB  - During the latest Latin American epidemic of cholera (1991), more than 70,000
      cases were identified and over 6,000 deaths occurred. Cholera started in Peru and
      expanded to the rest of Latin American countries, including Chile. Compared to
      Peru, the epidemic in Chile had minor consequences due to the strategies adopted
      by the National System of Health Services, together with other public
      institutions. These strategies included the establishment of a National Committee
      for Cholera, strategic planning of health services, strengthening of
      epidemiologic surveillance systems and of clinical and environmental
      laboratories, education of the population, and preventive strategies, among
      others. Maintenance of environmental health measures and the population's
      collaboration are essential to avoid future emergence of this disease.

PMID- 21186506
TI  - [Microbial portrait. Erysipelothrix rhusiopathiae].

PMID- 21186507
TI  - [Acute encephalopathy and brain death in a child with influenza A (H1N1) during
      the 2009 pandemic].
AB  - Since the World Health Organization declared a pandemic of a novel influenza A
      (H1N1) virus, much attention has been focused on its respiratory manifestations,
      but limited information regarding neurologic complications has been reported in
      children. We describe a case of acute encephalopathy progressing to brain death
      in a pediatric patient with confirmed infection with novel influenza A (H1N1).

PMID- 21186508
TI  - [Cat scratch disease associated neuroretinitis: clinical report and review of the
      literature].
AB  - Cat scratch disease is the main clinical presentation of Bartonella henselae
      infection. However, ocular manifestations of bartonellosis occur in about 5 to
      10% of the patients, mainly presenting as neuroretinitis, choroiditis or
      oculoglandular syndrome of Parinaud. We describe two patients with documented B.
      henselae infection and typical ocular compromise. Both patients were treated and
      had a favorable visual outcome.

PMID- 21186509
TI  - [Evaluation of children with tuberculosis contact].
AB  - Tuberculosis (TB) is a worldwide infectious disease, caused by Mycobacterium
      tuberculosis (Koch bacilli), that has re-emerged since the decade of the 80's in
      relation to the pandemic of HIV infection. Chile has one of the lowest TB
      prevalence rates in Latin America. In children, TB exhibits some differences from
      adult disease in terms of pathogenesis, clinical manifestations and probability
      of progression from the infected state to disease, making it more difficult to
      diagnose and increasing the likelihood of developing the disease once the
      infection is acquired. There is a National Program for the Prevention and Control
      of TB that allows us to develop prevention and chemoprophylaxis strategies. This
      article summarizes these strategies to guide the study and management of children
      in contact with TB patients.

PMID- 21186510
TI  - [Sir Arthur Conan Doyle, Sherlock Holmes and infectious diseases].
AB  - Besides a pleasant author of best sellers, Sir Arthur Conan Doyle was a medical
      doctor, writing excellent short stories about the exercise of his profession in
      England. However, even he mentions The British Medical Journal and The Lancet in
      the Sherlock Holmes's stories, when in the plot introduces infectious diseases,
      Conan Doyle ignores important discoveries in the field of tetanus. Anyway, the
      appearing of infectious diseases in the adventures of the detective are rare: one
      mention of tetanus, another of leprosy and- the most analyzed in medical
      literature a case of murder by inoculation of bacteria, probably the agent of
      melioidosis. Also he makes his hero discovers the toxic actions of a medusa and a
      transplant of solid organ. Little for a physician and less for an author who also
      wrote science fiction: it seems that the history of the great medical discoveries
      at the end of nineteenth century and beginning of the twentieth has passed by his
      side.., and he just couldn't see it.

PMID- 21186511
TI  - [Reasons for poor compliance with hand hygiene among hospital workers].

PMID- 21186512
TI  - [New and "old" antiretroviral drugs in Pediatrics: new doses, formulations and
      associations].
AB  - Of the 25 antiretroviral drugs available in the market, only 16 are allowed for
      prescription in the pediatric patients. The antiretroviral, pertaining to the
      first three families, used for two decades, remain valid and are important
      components of antiretroviral therapy in naive children. We describe doses,
      presentations and current associations for these drugs in children, and also
      discuss new co-formulations that will reduce the number of doses, improve
      tolerance and therefore achieve better adherence of pediatric patients.

PMID- 21186513
TI  - [Clinical guideline. Acquired immunodeficiency virus infection. Part III.
      Antiretroviral treatment for children and adolescents].

PMID- 21186514
TI  - [Expression and function analysis of dengue virus type 1 to 4 envelope domain III
      recombinant fusion protein].
AB  - OBJECTIVE: To observe the ability of dengue virus type 1-4 envelope domain III
      fusion protein to inhibit virus infection and analyze the neutralizing ability of
      polyclonal antibodies against rE III. METHODS: After being connected by linker
      peptide, E III protein of Dengue virus serotypes 1-4 were expressed in E coli
      BL21 (DE3) then purified. Fusion proteins were verified by Western Blot and
      ELISA. Rabbits were immunized with fusion proteins to produce anti-rE III serum.
      The activity of anti-rE III serum were detected through indirect
      immunofluorescence assay test. Inhibition of dengue virus type 1 to 4 infection
      in BHK-21 cells by rE III fusion protein were tested. Neutralizing activity of
      anti-rE III serum was analyzed. RESULTS: Dengue virus type 1 to 4 envelope domain
      III recombinant fusion protein was expressed in E coli BL21 and purified
      successfully. Then rE III fusion protein and anti-rE III serum were analyzed
      respectively and rE III fusion protein can effectively inhibit dengue virus type
      1 to 4 from infecting BHK cells. The anti-rE III serums can neutralize dengue
      virus type 1 to 4 but with different neutralizing titer. CONCLUSION: Dengue virus
      type 1-4 envelope domain III fusion protein can directly inhibit DV infection.
      Antibodies induced by rE III fusion proteins can neutralize dengue virus type 1
      4.

PMID- 21186515
TI  - [Interaction between various 14-3-3beta segments and PrP in vitro].
AB  - OBJECTIVE To study the potential interaction between PrP protein. METHODS: The
      supernatant of health and scrapie-infected hamsters' brain homogenate was
      prepared, while various recombinant 14-3-3beta or PrP proteins were purified. The
      possible molecular interaction between 14-3-3beta proteins and PrP was tested by
      pull-down and immunoprecipitation assays. RESULTS: Both native PrP(c) and its
      protease-resistant isoform (PrP(Sc)) formed complexes with 14-3-3beta. The full
      length recombinant 14-3-3beta proteins interacted with PrP. The domain
      responsible for interacting 14-3-3beta was located at N-terminal of 14-3-3beta
      (residues 1 to 38). CONCLUSION: The studies of the association of PrP with 14-3
      3beta may further provide insight into a potential role of 14-3-3beta in the
      biological function of PrP and the pathogenesis of prion disease.

PMID- 21186516
TI  - [Expression and purification of EBV-LMP2 protein].
AB  - OBJECTIVE: To obtain a second Epstein-Barr virus membrane protein (LMP2) in
      insect cells. METHODS: The full length EBV-LMP2 gene was inserted into
      baculovirus expression transfer vector pFastBac HT B to obtain the recombinant
      baculoviruses Bac-LMP2. And generation of recombinant baculoviruses was followed
      by transfection of the recombinant Bac-LMP2 into insect cells, then the
      recombinant LMP2 protein was recognized by SDS-PAGE and western blot. The
      expressed LMP2 protein was purified by one step with Ni-NTA metal chelation
      chromatography. RESULTS: The expressed LMP2 protein was confirmed by SDS-PAGE and
      western blot. The purity of purified LMP2 protein is up to 86% by HPLC analysis.
      CONCLUSION: The EBV-LMP2 was expressed in insect cells, and the purified LMP2
      protein was obtained.

PMID- 21186517
TI  - [The expression and preliminary evaluation of HPV6bL2deltaN360E7E6 fusion protein
      in E. coli for genital warts].
AB  - OBJECTIVE: To express HPV6bL2deltaN360E7E6 fusion protein in E. coli and
      preliminarily evaluate its immune effect. METHODS: Three HPV6b gene fragments,
      which were L2(1-360 bp), E7 and E6, were fused by overlapping PCR, then were
      inserted into a prokaryotic expression vector and expressed in E. coli. C57BL/6
      mice were immunized with purified fusion protein plus Al (OH)3 and/or CpG
      adjuvants through intramuscular route, the cellular and humoral immune responses
      were detected by IFN-gamma ELISPOT and ELISA respectively. RESULTS: Protein plus
      CpG adjuvant could induce the strongest cellular immune response to E7 and E6,
      high antibody titer against L2 could be detected in all immunized groups but
      there were no significant difference among these groups. CONCLUSIONS:
      HPV6bL2deltaN360E7E6 gene was successfully cloned into pQE30 vector and expressed
      in E. coli, the fusion protein was also purified and proved that could induce
      strong cellular and humoral immune responses with appropriate adjuvant in C57BL/
      6 mice and could be used for future research.

PMID- 21186518
TI  - [Screening and application of prokaryotic enhancer-like sequence 3A].
AB  - OBJECTIVE: To screen enhancer-like sequences from Escherichia coli strain C600
      genome, to construct an expression vector harboring prokaryotic enhancer-like
      sequence and study the effect of interferon gene expression. METHODS: Enhancer
      like element from Escherichia coli strain C600 genome was obtained by using the
      chloramphenicol acetyl-transferase (CAT) gene as reporter gene. An expression
      vector harboring prokaryotic enhancer-like sequence from Escherichia coli strain
      C600 was constructed. Interferon was expressed and assayed. RESULTS: An enhancer
      like sequences with distance and orientation independence property were screened
      and named 3A. Quantification test showed that the direct and reverse orientation
      of 3A could increase the activity of beta-galactosidase with 7.11 and 2.93 times.
      The enhancing activity of the element was on transcription level. An expression
      vector harboring the prokaryotic enhancer-like sequence 3P3 which was enhancing
      function region of sequence 3A was constructed. Using this vector the antiviral
      activity of interferon alpha-2b was increased by 3.7 times in comparison with the
      original expression plasmid. CONCLUSION: 3A enhancer-like sequence was screened
      from Escherichia coli strain C600 genome. Interferon gene was highly expressed by
      using an expression vector harboring enhancer-like sequences.

PMID- 21186519
TI  - [Association between HBV genotype and chronic/severe liver disease with HBV
      infection in Chinese patients].
AB  - OBJECTIVE: To explore the association between HBV genotype and chronic/severe
      liver disease with HBV infection in Chinese patients. METHODS: Serum samples were
      collected from 2922 patients with HBV infection. HBV genotyping was performed
      with type-specific primers polymerase chain reaction, and the virological and
      biochemical markers were detected, which differences in the genotypes between
      various clinical types of HBV infection and liver function and virological
      markers between various HBV genotyping were analyzed. RESULTS: The genotype B, C,
      BC combinations, D of 2922 patients with HBV infection accounted for 15.9%,
      83.5%, 0.41%, 0.21% respectively. The ratio of genotype B in acute hepatitis
      group was higher (P = 0.003), which the ratio of genotype C in the cirrhosis
      group and the hepatocellular carcinoma group was higher (P = 0.000, 0.000). The
      difference in ratio of genotype C was not statistically significant between acute
      on-chronic liver failure group and chronic hepatitis group. HBeAg-positive rate,
      viral load and liver function markers of B, C genotype group in acute hepatitis
      group and chronic hepatitis group were not significant different. HBeAg-positive
      rates of genotype C in acute-on-chronic liver failure group, cirrhosis group,
      hepatocellular carcinoma group were higher than that of genotype B (P = 0.000,
      0.024, 0.003). Viral load of genotype C in hepatocellular carcinoma group was
      higher than that of genotype B (P = 0.025). Cholinesterase levels of genotype C
      in the acute-on-chronic liver failure group and the hepatocellular carcinoma
      group was lower than that of genotype B (P = 0.0004, 0.02). CONCLUSION: There
      were HBV genotype B, C, B/C combinations and D in Chinese patients with HBV
      infection, with genotype B and C being the major ones. Compared with HBV genotype
      B, genotype C in Chinese patients with HBV infection was more likely to chronic
      infection, evolved to cirrhosis and hepatocellular carcinoma, but genotype
      difference was not observed in occurrence of acute-on-chronic liver failure.
      Genotype was not significant effect in acute and chronic hepatitis B, but HBeAg
      positive rate/viral load was higher and liver damage was more severe in severe
      and end-stage genotype C HBV infection patients.

PMID- 21186520
TI  - [Study on the changes of the T-lymphocyte subsets and their significance in
      influenza A (H1N1) virus patients].
AB  - OBJECTIVE: To study the changes of T-Lymphocyte and activated T-Lymphocyte
      subsets in influenza A (H1N1) virus patients. METHODS: The percentages of the
      subsets of Lymphocyte were detected by flow cytometry in influenza A (H1N1) virus
      patients (n = 144) and normal controls (n = 41). Furthermore, the subsets of T
      Lymphocyte and activated T-lymphocyte were analyzed in 83 among those patients
      before and after treatment. RESULTS: Compared with the control group, the counts
      of Lymphocyte in patients with influenza A (H1N1) virus was significantly
      discreased, the counts of Lymphocyte in patients with influenza A virus
      concurrent pneumonia was significantly discreased those of no concurrent
      pneumonia; Compared with the control group, the percentage of T-lymphocyte in
      patients with influenza A virus concurrent pneumonia was significantly
      discreased. The counts and percentage of CD3 and CD8 cells was significantly
      discreased in patients (n = 83) before treatment; The counts of CD4 cells was
      significantly discreased before treatment. The percentage of HLA-DR+ CD+, HLA-DR+
      CD4+ and HLA-DR+ CD8+ cells was significantly discreased in patients (n = 83)
      before treatment. CONCLUSIONS: To understand the expression of the T-Lymphocyte
      and activated T-Lymphocyte subsets in influenza A (H1N1) virus patients may help
      to evaluate the patients' cellular immune status, but also be a guideline of
      early diagnosis of Influenza A (H1N1) virus.

PMID- 21186521
TI  - [Study on the relationship between HBV viral loads and the changes of liver
      pathological features in patients with HBeAg-negative chronic hepatitis B].
AB  - OBJECTIVE: To investigate the relationship between serum HBV DNA loads and liver
      histology damage in the patients with HBeAg-negative chronic hepatitis B.
      METHODS: The retrospective study was performed. The 514 patients were divided
      into two groups according to the HBeAg status and the HBeAg positive group was as
      control. The relationship among HBV DNA loads, live histological inflammation
      grades and fibrosis stages was analyzed. RESULTS: The HBV DNA loads in HBeAg
      negative group and HBeAg-positive group were (5.38 +/- 1.27) log10 copies/ml and
      (6.80 +/- 1.18) log10 copies/ml respectively (P < 0.001). The inflammation grades
      and fibrosis stages of liver tissues in HBeAg-negative group were all
      significantly higher than those in HBeAg-positive group (P < 0.001). In HBeAg
      negative group, HBV DNA loads displayed a positive correlation with the
      inflammation grades and fibrosis stages of liver tissues (P < 0.001). CONCLUSION:
      In the patients with HBeAg-negative chronic hepatitis B, HBV viral loads are
      lower than those with HBeAg-positive chronic hepatitis B, and HBV viral loads
      display a positive correlation with liver the inflammation grades and fibrosis
      stages of liver tissues.

PMID- 21186522
TI  - [Study on immunogenicity of DNA vaccine encoding human cytomegalovirus gB and
      pp150 fusion gene].
AB  - OBJECTIVE: To provide experimental evidence for development of human
      cytomegalovirus (HCMV) nucleic acid vaccine, HCMV surface protein (gB), membrane
      protein (pp150), and gB-pp150 fused gene eukaryotic expression vector were
      constructed. METHODS: gB and pp150 genes were amplified and fused into gB-pp150,
      then were cloned into pcDNA 3.1 (+) to obtain recombinant expression plasmids
      pcDNA 3.1 (+) -gB, pcDNA 3.1 (+) -pp150 and pcDNA 3.1 (+) -gB-pp150, which were
      encapsulated with chitosan. Mouse were vaccinated and the humoral and cell immune
      response were determined by ELISA, specific proliferative response of plenic
      lymphocytes. RESULTS: The gB, pp150 and gB-pp150 fusion gene eukaryotic
      expression vector were successfully constructed. The antibodies A value induced
      by pcDNA3.1(+) -gB or pcDNA3.1 (+) -gB-pp150 were much higher than that of
      pcDNA3.1 (+) (P < 0.01). The IFN-gamma levels induced by pcDNA3.1 (+) -pp150 and
      pcDNA3.1 (+) -gB-pp150 were significantly higher than that of pcDNA3.1 (+). There
      are significant diference between the stimulating indexes of pcDNA3.1(+) -pp150
      or pcDNA3.1 (+) -gB-pp150 immunized and normal mice. CONCLUSION: The DNA vaccine
      pcDNA3.1 (+) -gB can induce significant humoral immunity response, and pcDNA3.1
      (+) -pp150 can induce high cellular immune response, whereas pcDNA3.1 (+) -gB
      pp150 can induce both humoral and cellar immune responses in BALB/c mice.

PMID- 21186523
TI  - [Analysis the relationship of HBV BCP A1762T/G1764A double mutation with HBV
      related acute on chronic liver failure].
AB  - OBJECTIVE: To analysis the relationship between HBV BCP A1762T/G1764A double
      mutation with acute on chronic liver failure (ACLF). METHODS: HBV BCP
      A1762T/G1764A double mutation was detected in 166 HBV chronic infection patients
      by nested PCR and direct DNA sequencing. The mutation rate was compared among the
      patients with different disease course. RESULTS: Among 166 patients, 45 patients,
      45 patients, 49 patients and 27 patients were diagnosed as chronic hepatitis B
      (CHB), liver cirrhosis (LC), ACLF and hepatocellular carcinoma (HCC),
      respectively. A1762T/G1764A double mutation rate was 40.0% (18/45), 84.4%
      (38/45), 73.5% (36/49) and 92.6% (25/27) respectively in different groups.
      However, A1762T/G1764A double mutation rate has no difference between ACLF based
      on CHB and LC (P = 0.502) and between patients with HBeAg positive and negative
      (P = 0.735). HBV DNA level (log) of patients with A1762T/G1764A double mutation
      was 5.68 +/- 1.36, lower than but having no significant statistic difference
      compared to patients without the double mutation (6.14 +/- 1.81, P = 0.075).
      CONCLUSION: A1762T/G1764A double mutation has a close relationship with the
      progress of HBV-infection diseases, but is not specific to patients with ACLF.
      And patients with BCP double mutation have similar HBV DNA levels and HBeAg
      status with patients without the double mutation.

PMID- 21186524
TI  - [Construction and experimental study on off-line hybrid bioartificial liver
      supporting system with human liver cell line].
AB  - OBJECTIVE: To construct an off-line hybrid bioartificial liver supporting system
      with human liver cell line, and study it's effect on the plasma from patients
      with liver failure. METHODS: We established the bioreactor using Psu-2s
      (Fresenius) cultured with Hep G2 cell transfected with human augmenter of liver
      regeneration (hALR) gene, then constructed a hybrid bioartificial liver
      supporting system, at last using the bioartificial liver support system to purify
      the plasma treated 2 hours with serum bilirubin absorbent, separated from acute
      on chronic liver failure patients infected by hepatitis B virus. RESULTS:
      Bioreactor was successful constructed. The cell viability in perigastrum of
      bioreactor is 85.2% and cell propagated rapidly. Before and after treating with
      bilirubin absorbent, serum total bilirubin was (176.19 +/- 54.14) micromol/L and
      (50.1 +/- 16.85) micromol/L respectively (P = 0.0002). While there were no
      significance difference in the level of albumin, urea and glucose. At the begin
      and end of treatment with bioartificial liver, serum total bilirubin was (50.10
      +/- 16.85) micromol/L and (30.27 +/- 15.02) micromol/L respectively (P = 0.000),
      the urea and albumin increased, urea has significantly difference, but the change
      of albumin hasn't. CONCLUSION: The off-line hybrid bioartificial liver supporting
      system with human liver cell line were builded successfully and have synthesis
      and metabolism functions for acute on chronic liver failure patients.

PMID- 21186525
TI  - [The dissemination of CMV in urine of different group from Guangxi and the
      relationship between CMV infection and renal disease].
AB  - OBJECTIVE: To detect Human Cytomegalovirus (HCMV) DNA in urine samples from the
      following groups: pregnant women, sick newborns, hospitalized nephropathy
      patients, renal transplant recipients and normal population. Preliminarily study
      the relationship of HCMV infection and renal disease. METHODS: To detect HCMV DNA
      in morning urine samples by Real-time fluorescence quantitative PCR (FQ-PCR).
      RESULTS: The positive rates of HCMV DNA in the urine of pregnant women,sick
      newborns, hospitalized nephropathy patients, renal transplant recipients and
      normal population are 8.18%, 3.45%, 18.54%, 25.42%, 0.56%. CONCLUSION: The
      infection rates of HCMV in the urine of pregnant women and sick newborns are very
      high in Guangxi, it should take serious measures to prevent and control the
      situation. HCMV probably participate in the injury of kidney, and worsen the
      disease. It should be one of the causes of renal disease.

PMID- 21186526
TI  - [Study on the inhibition effect of siRNA on herpes simplex virus type 2 ICP4
      gene].
AB  - OBJECTIVE: To explore the inhibition effect of RNA interference on the ICP4
      expression and DNA replication of herpes simplex virus type 2 (HSV2). METHODS:
      Four pairs of siRNA targeted to HSV2 ICP4 gene and negative control siRNA were
      synthetized by chemical method, named as siRNA-1, siRNA-2, siRNA-3, siRNA-4 and
      siRNA-N respecticely. HSV2 HG52 was used to attack Vero cell after transfection
      overnight. Vero cell and supernatant were collected at 1d, 2d, 3d, 4d and 5d
      after virus attacking. Flurogenic quantitative reverse transcription polymerase
      chain reaction (FQ-RT-PCR)was used to detect the expression of HSV2 ICP4 mRNA,
      flurogenic quantitative polymerase chain reaction(FG-PCR) was used to detect the
      expression of HSV2 DNA and Western-Blot was used to detect the expression of HSV2
      ICP4 protein. RESULTS: All the four pairs of siRNA could significantly inhibit
      the expression of HSV2 ICP4 mRNA and protein, especially siRNA-2. The above
      siRNAs could significantly decrease HSV2 DNA copy number,too. CONCLUSION: siRNAs
      targeted to HSV2 ICP4 gene could significantly inhibit expression of HSV2 ICP4
      mRNA and protein, and decrease HSV2 DNA copy number, suggesting that siRNA can
      inhibit HSV2 DNA replication through silencing ICP4 gene.

PMID- 21186527
TI  - [Detecting the occult HBV infection: a laboratory study].
AB  - OBJECTIVE: To see the HBV DNA detection instance in the HBsAg negative people and
      to study the serological method detection strategy for detecting hepatitis B
      virus large surface protein (HBLP) to filtrate the occult HBV infection. METHODS:
      The HBsAg negative serum samples were divided into HBsAb negative and positive
      two species according to the hepatitis B virus markers (HBVM) in daily work
      excepting the special HBVM modes. Total 2000 stochastic serum samples with 1000
      HBsAb negative results and 1000 HBsAb positive results were collected from the
      copy tubes to detect HBVM with national ELISA reagent kits and put them -20
      degrees C frostily. Mixed samples (8 x 30 microl) were analyzed with fluorescence
      quantitative PCR (FQ-PCR) and filtrated the individual positive samples. The
      filtrated samples were doubly tested again with American MONOLISA HBsAg ULTRA
      reagents. RESULTS: No HBV DNA positive results were found out from the 1000 HBsAb
      positive samples and 19 cases HBV DNA positive results were found out from the
      1000 HBsAb negative samples. On these 19 samples, the HBsAg results from the
      American MONOLISA HBsAg ULTRA reagents were all positive and the HBLP results
      were all positive, too. The 19 HBV DNA quantitative results were divided into 2
      cases more than 500 copies/ml, 3 cases between 400-500 copies/ ml, 3 cases
      between 300-400 copies/ml, 7 cases between 200-300 copies/ml and 4 cases between
      100-200 copies/ml. CONCLUSION: The leaked samples tested HBsAg with national
      reagents are mostly from the HBsAb negative people. HBLP results may be positive
      on these samples and detecting HBLP marker is propitious to filtrate the occult
      HBV infection. This study provided a kind of serological reference for actively
      searching for the detecting strategy in occult HBV infection field.

PMID- 21186528
TI  - [Lamivudine and entecavir significantly improved the prognosis of early-to-mid
      stage hepatitis B related acute on chronic liver failure].
AB  - OBJECTIVE: To clinically study the antiviral effects of lamivudine and entecavir
      on patients with early-to-mid stage Hepatitis B related acute on chronic liver
      failure (HBV-ACLF). METHODS; A prospective, randomized, open and parallel
      controlled clinical trial was designed to observe the antiviral effects of
      nucleoside analogues on patients with early-to-mid stage HBV-ACLF. Three groups
      were set for controlled study, i. e. basic treatment group, lamivudine plus basic
      treatment group and entecavir plus basic treatment group. RESULTS: One month
      after treatment, the improvement rates of lamivudine group and entecavir group
      were 58.85% and 59.15% respectively, significantly higher than that of basic
      treatment group which was 34.84% (Chi(2) = 9.8323, P = 0.043). By the end of six
      months, the cumulative survival rates of patients with the antiviral treatments,
      i.e., lamivudine, entecavir, were 65.8%, 60.1%, significantly higher than that
      (42%) without the antiviral treatment (P = 0.045, P = 0.04 respectively). The
      cumulative survival rate in patients with a MELD score < 30 was higher than that
      with a MELD score over 30 (Chi(2) = 3.920, P = 0.048). For the patients with
      pretreatment HBV DNA > or = 10(7), the cumulative survival rate in patients with
      entecavir treatments group was higher than that of patients in basic treatment
      group (Chi(2) = 5. 014 P= 0.025). According to the Ordinal Regression analysis,
      antiviral therapy by using either lamivudine or entecavia could significantly
      increase the improvement rate of patients with early-to-mid stage HBV-ACLF. But
      severe complications, including hepatorenal syndrome, electrolyte imbalance and
      hepatic encephalopathy, medical history of liver cirrhosis, and pretreatment HBV
      DNA > or = 10(7) had significant impacts on prognosis of this group patients.
      CONCLUSIONS: Antiviral therapy by using either lamivudine or entecavia could
      significantly increase the survival rate of patients with early-to-mid stage HBV
      ACLF.

PMID- 21186529
TI  - [Key points of nursing HbeAg negative cirrhotic patients with nucleot (s) ide
      analogues antiviral therapy].
AB  - OBJECTIVE: To explore the key points of nursing HBeAg negative cirrhotic patients
      with nucleot(s) ide analogues antiviral therapy. METHOD: Patients enrolled into
      this study were divided into antiviral group (58 cases) and control group (53
      cases). Patients from control group only received the supportive and symptomatic
      treatment and those from antiviral group received the additional nucleot (s) ide
      analogues treatment. All patients were observed during hospitalization and were
      followed up in clinic. Finally, we would make a nursing assessment. RESULTS: All
      patients finished the 96-week treatment and follow-up, except 6 patients died.
      Alanine transferase normalization rate and HBV DNA decline were more remarkable
      in antiviral group than that in control group. HBV DNA negative( <500 copies/ml)
      after 96-week treatment were 88.7% in antiviral group and 32. 5% in control group
      respectively(Chi(2) = 31.427, P = 0.001). CONCLUSION: Nucleot(s) ide analogues
      are significantly effective to inhibit HBV DNA replication in HBeAg negative
      cirrhotic patients and improve liver function. The key points of nursing these
      patients including appropriate patients' educating, benign nurse-patient
      relationship building, medical compliance emphasizing, and attentive complication
      observing and dealing.

PMID- 21186530
TI  - [Analysis of 96 cases with novel H1N1 influenza A].
AB  - OBJECTIVE: To review the epidemiologic and clinical characteristics of 96 cases
      with novel H1N1 influenza A, and improve the diagnosis and treatment level of
      novel H1N1 influenza A. METHODS: 96 cases of novel H1N1 influenza A admitted to
      the isolation wards from Oct 20 to Sep 23, 2009 were studied. Their
      epidemiologic, clinical, laboratory, and radiologic characteristics were
      analyzed. RESULTS: The median age of the 96 patients was 26.52 +/- 10.62 years
      (range, 5 to 60 years). Sixty-four of the 96 patients had a close contact with
      novel H1N1 influenza A patients. The main symptoms included fever 100%, cough
      86.4% , sore throat 66.6% and myalgia 32.3%. CONCLUSION: The clinical
      presentation of novel H1N1 infection is largely indistinguishable from that of
      seasonal influenza. Combines both a symptom complex with the epidemiological
      investigation and laboratory characteristics can improve the accuracy of
      diagnosis of novel H1N1 influenza A.

PMID- 21186531
TI  - [Value of FIB-4 for the diagnosis of liver fibrosis in chronic hepatitis B].
AB  - OBJECTIVE: To assess the diagnostic value of FIB-4 in chronic hepatitis B (CHB)
      by comparing their results with histological features. METHODS: 212 chronic
      hepatitis B patients underwent liver biopsy with a blood sample taken
      simultaneously. The serum level of ALT, AST, PLT were tested. These results
      together with age of the patients were put into the formula and final results of
      FIB-4 were computed. Three different endpoints were studied according to liver
      fibrosis stage, namely significant fibrosis (S2 to s4), extensive fibrosis (S3 to
      S4) and cirrhosis (S4). With liver biopsy as the gold standard, ROC curves were
      delineated for different endpoints. The area under the ROC curves reflected its
      diagnostic values. RESULTS: The distribution of their fibrosis stage was as
      follows, S0:3 (1.4%); S1:49 (23.1%); S2:66 (31.1%); S3:50 (23.6%); S4:44 (20.8%).
      That means 160 patients (75.5%) had significant fibrosis (S2 to S4), 94 (44.3%)
      had extensive fibrosis (S3 to S4) and 44 (20.8%) had cirrhosis (S4). The AUCs of
      FIB-4 for significant fibrosis, extensive fibrosis and cirrhosis were 0.733 (95%
      CI: 0.660-0.806, P < 0.01), 0.746 (95% CI: 0.679-0.813, P < 0.01), 0.756 (95% CI:
      0.687-0.825, P < 0.01) respectively. CONCLUSION: The FIB-4 index is a simple,
      accurate and inexpensive methed to assess liver fibrosis in chronic hepatitis and
      may reduce the need for liver biopsy.

PMID- 21186532
TI  - [The analysis of clinical character in different age patients suffered from A
      H1N1].
AB  - OBJECTIVE: To describe the feature of different age patients with A-H1N1.
      METHODS: Cross-sectional study was performed in 95 patients who were confirmed to
      be infected with A-H1N1 from May, 2009 to July, 2009, in according to their age.
      RESULTS: The average age of patients with A-H1N1 infection was 23.44 +/- 14.73.
      Accumulative prevalence in children and young adult reached 74.7% of total
      patients. There was a trend that the subclinical infection rate raised gradually
      from 0-15 years group to over 45 years group. The percent of lymphocyte in 0-15
      years group was significantly higher than other age groups, P = 0.039. The
      average time of virus shedding were 6.5 +/- 2.10 days (from 2 days to 12 days) ,
      and there were no significant difference in diverse age groups, P = 0.272. 13 out
      of 95 (13.7%) patients presented complications related with A-H1N1 infection, and
      4 of 6 patients complicated with pneumonia were in the 0-15 years group.
      CONCLUSION: The distribution of age in A-H1N1 infection is markedly different
      from seasonal influenza, with more cases in school children and young adults and
      fewer cases in older adults. Flu-like symptoms in children were apparent and
      pneumonia was the major complication in children.

PMID- 21186533
TI  - [Occult HBV infection in patients with anti-HBc positive alone].
AB  - OBJECTIVE: This study was designed to explore the incidence rate of occult HBV
      infection in patients with anti-HBc positive alone and analyze the possible
      reasons of occult infection. METHODS: Sera of 183 patients carrying anti-HBc
      alone(A < or = 0.1) were collected and real-time PCR was used to select samples
      with HBV DNA positive. HBV pre-S/S amplification products were obtained by PCR,
      and clonal sequencing were then used for these samples with HBV DNA positive.
      RESULTS: DNA quantitative results of three samples were greater than 10(3)
      copies/ml in 183 samples, with a fraction of 1.6%. Pre-S/S sequencing results of
      two samples from these three samples were obtained. Point mutations within "a"
      determinant with Q129R/P mutations and co-existence of the mutant type and wild
      type were found in the two samples. CONCLUSIONS: Occult HBV infection existed in
      samples with anti-HBc alone. Factors contributing to the loss of HBsAg detection
      by immunoassays include S gene mutations and low levels of circulating antigen
      which are below the assay limit of detection. Occult HBV infection not only can
      lead to a false clinical diagnosis, but also can result in hematological
      pollution due to such occult infection of blood donors.

PMID- 21186534
TI  - [Efficacy of the 96-week adefovir dipivoxil therapy in patients with chronic
      hepatitis B].
AB  - OBJECTIVE: To investigate the efficacy of the 96-week antiviral therapy with
      adefovir dipivoxil in patients with chronic hepatitis B. METHODS: 80 patients
      with chronic hepatitis B received the antiviral therapy of adefovir dipivoxil
      (ADV, 10 mg/d). At the 12th week, 19 cases without early viral response (EVR, HBV
      DNA drop < 2 log10copies/ml) switched to the therapy of other nucleoside
      analogues. Aminotransferase (ALT) normalization, HBV DNA negative, HBeAg loss and
      HBeAg seroconvertion were accessed at the 96th week. RESULTS: At week 96, ALT
      normalization and HBV DNA negative in 61 patients with ADV therapy were 85.25%
      (52/61) and 95.08% (58/61); and HBeAg loss and HBeAg seroconvertion were 52.52%
      (17/33) and 42.42% (14/33) respectively. While for the other 19 patients
      switching to other nucleoside analogues, ALT normalization and HBV DNA negative
      came to 57.89% (11/19) and 68.42% (13/19). Both HBeAg loss and HBeAg
      seroconvertion were 58.33% (7/12). CONCLUSION: Long term ADV antiviral therapy is
      effective to inhibit HBV DNA replications and benefits patients with chronic
      hepatits B. Switching to another nucleoside analogue is an optimal alternative if
      there is no EVR at week 12 in ADV therapy.

PMID- 21186535
TI  - [The treatment research of people with different types of HPV infection in
      sterile patients].
AB  - OBJECTIVE: Explore the optimal treatment of infertility patients infected with
      different types of human papillomavirus (HPV). METHODS: According to cervical
      pathology, cervical status and the procreate desire of the infertility patients,
      the 144 clinic cases of high-risk human papillomavirus infected infertile
      patients were divided into two gruoups: group with treatment and without
      treatment. Real-time quantitative fluorescent PCR (RT-PCR) has been employed,
      follow-up time is 6 months, to detect the HPV-DNA in the crevical exfoliated
      cells, to observe the negative conversion rate and pregnancy rate, and compare
      analyzed. RESULTS: (1) In high-risk HPV infectors, the negative conversion rate
      of treatment group (56.67%) is higher than those in non-treatment group (50.00%);
      (2) The pregnancy rate of secondary high-risk HPV non-treatment group (50.00%) is
      higher than the treatment group. The pregnancy rate of primary high-risk HPV
      treatment group (31.67%) is higher than the non-treatment group (4.00%). (3)
      Negative conversion rate increases accordingly, on primary high-risk HPV infected
      groups with Leep, with single drug and with Leep combined with drug therapy. (4)
      The negative conversion rate and the pregnancy rate of primary high-risk HPV
      infected groups with surgical therapy is higher than the groups with drug
      therapy. Surgical + Drugs is better in the two surgical therapies. CONCLUSION:
      Infertile patients should be routinely screened for cervical HPV. The primary
      high-risk cervical HPV infection is the etiology of infertility. Preferably,
      patients with primary high-risk HPV infection in cervical lesions is treated with
      Leep combined drugs.

PMID- 21186536
TI  - [Observation on effect of peg interferon lphaa-2a treating lamivudine resistant
      chronic hepatitis B].
AB  - OBJECTIVE: To observe the efficacy and safety of PEG-interferon alpha-2a (PEG
      IFNalpha-2a) treatment on lamivudine (LAM)-resistant chronic hepatitis B (CHB)
      patients. METHODS: Eighty-one patients with lamivudine-resistant HBeAg (+)
      chronic hepatitis B patients were enrolled and divided into PEG-IFNalpha-2a
      treatment group (40 cases) and adefovir dipivoxil (ADV) control group (41 cases).
      Two groups were combined with LAM in the first 12 weeks(w). The ALT normalization
      rate, the HBV DNA and HBeAg negative rate, and the HBeAg seroconversion rate were
      observed in 12 W, 24 W, 48 W. RESULTS: The ALT normalization rate in 12 W, 24 W
      of PEG-IFNalpha-2a group was 62.5% and 80.0%. And it was higher than that of ADV
      group. The HBeAg negative rate and HBeAg seroconversion rate in 48 W of PEG
      IFNalpha-2a group were 60% and 57.5% , which were higher than that of ADV group.
      The difference was statistically significant (P < 0.05). CONCLUSION: PEG-IFNalpha
      2a treatment of lamivudine-resistant HBeAg (+) chronic hepatitis B is superior to
      ADV, and its security is well.

PMID- 21186537
TI  - [Construction and expression of lentiviral vector of rat beta-defensin-2 gene].
AB  - OBJECTIVE: To construct a lentiviral expression vector of rat beta-defensin-2
      (rBD2) gene, and examine its expression by transfected cultured cells, in order
      to lay the foundation for experiments in vivo. METHODS: The total RNA of rat
      epithelial cells was extracted and rBD2 gene was got with PCR amplification.
      After double-digested and connected the PCR production and lentiviral vector
      Lentivirus [containing H1 promoter and green fluorescent protein (GFP)], the
      lentiviral expression vector of rBD2 gene LV-rBD2 was constructed and confirmed
      by sequencing. The virus-like particles of LV-rBD2 was packed with lentiviral
      packaging systems and viral titer was determinated by slow-gradient dilution.
      Expression of rBD2 was tests with RT-PCR and Western Blot after cultured cells
      had been infected by LV-rBD2. RESULTS: The results of gel electrophoresis and DNA
      sequencing showed that the rBD2 gene was cloned into the lentiviral vector, the
      sequence is correct. The lentiviral vector particle packaging was complete, the
      virus titer was adjusted to 1 x 10(5) ifu/microl. RT-PCR and Western-blot showed
      that rBD-2 gene was expressed. CONCLUSION: The lentiviral expression vector of
      rBD2 gene LV-rBD2 was constructed successful, and could transfect cells to
      express rBD2.

PMID- 21186538
TI  - [Development of a rapid test kit for antibody to HIV by nano immunomagnetic
      lateral flow method].
AB  - OBJECTIVE: To develop a rapid test kit for antibody to HIV by nano immunomagnetic
      lateral flow method. METHODS: A rapid test kit was developed by conjugation of
      the HIV antigen gp41 and gp36 to 200nm super paramagnetic particles by
      carbodiimide (EDC) and coating of the HIV antigen gp41 and gp36 to nitrocellulose
      membrane. Then the kit was evaluated with serials of experiments. RESULTS: The
      kit was qualified with examination of national reference panel of anti-HIV
      antibody for colloidal gold diagnostic kit. The sensitivity was 100% by tested
      with 20 HIV antibody positive sera, the specificity was 98.5% by tested with 600
      HIV antibody negative sera, respectively. The stability of the kit was over 12
      month by storage at room temperature. CONCLUSION: A diagnostic kit for antibody
      to HIV was developed with the advantages of convenience, rapid test, good
      stability and point of care.

PMID- 21186539
TI  - [Vitamin D--physiological importance].
AB  - Vitamin D is a hormone by its chemical, characteristics, the pathway and
      regulation of synthesis, storage, specific receptor in the target cells and their
      mechanisms. vitamin D as a hormone regulates calcium and phosphates homeostasis,
      and maintains regulates calcium and phosphates homeostasis, and maintains density
      and strength of bones, it also regulates the following: regulates composition and
      function of muscles (heart and skeletal) and of skin, metabolism (fat tissue and
      blood lipids, insulin and blood sugar), immune functions (in infection and
      autoimmune diseases), and it prevents cancer diseases and regulates cognitiove
      functions and mood-disorders (depression, dementia).

PMID- 21186540
TI  - [Problem of creation of arteriovenous fistulae for hemodialysis in older
      patients].
AB  - INTRODUCTION: A significant problem in elderly on hemodialysis is vascular access
      creation. The aim of the study was to determine the factors of functionality of
      arteriovenous fistulas in elderly people. MATERIAL AND METHODS: Target groups in
      the four-year study were patients over 65 years of life. The authors analyzed the
      demographic structure, the etiology of kidney weakness, the type of anastomosis,
      arteriovenous fistula location, use of catheters from hemodialysis, blood
      pressure and size of the lumen of blood vessels used for anastomosis. Routine
      hematological and biochemical parameters were determined in all subjects. The
      study included 120 patients, 42 (35%) women and 78 (65%) men. RESULTS: Functional
      arteriovenous fistulae were found in 62 (51.70%) patients, aged 72.5 +/- 4.23
      years and nonfunctional ones in 58 (48.3%) respondents aged 72 +/- 5.09 years. A
      significant difference between the studied groups was reached in relation to the
      type of anastomosis (p = 0.005) and sites of the located fistulas (p = 0.03).
      Hypertensive nephropathy occurs statistically significantly more frequently in
      patients with functional fistula (p = 0.03). Sedimentation (p = 0.01), hemoglobin
      (p = 0.04), platelets (p = 0.003), total cholesterol (p = 0.04) and low density
      lipoproteins (p = 0.03) had statistically higher values in patients with
      nonfunctional fistulae. CONCLUSION: Atherosclerosis and increased coagulation in
      the old people on hemodialysis represent an important cause of complications of
      arteriovenous fistulae.

PMID- 21186541
TI  - [Functional hearing examinations in patients suffering from diabetes mellitus
      type 1 in regard to disease duration].
AB  - INTRODUCTION: Problems of hearing disturbances in persons suffering from diabetes
      have been attracting great attention for many decades. MATERIAL AND METHODS: In
      this study we examined the auditory function of 50 patients suffering from
      diabetes mellitus type 1 of different duration by analyzing results of pure-tone
      audiometry and brainstem auditory evoked potentials. The obtained results of
      measuring were compared to 30 healthy subjects from the corresponding age and
      gender group. The group of diabetic patients was divided according to the disease
      duration (I group 0-5 years; II group 6-10 years, III group over 10 years).
      RESULTS AND DISCUSSION: A statistically significant increase of sensorineural
      hearing loss was found in the diabetics according to the duration of their
      disease (I group = 14.09%, II group = 21.39%, III group = 104.89%). The results
      of the brain stem auditory evoked potentials, the significance threshold being p
      = 0.05 between the controls and the diabetics at all levels of absolute latency
      of right and left sides, did not show significant differences in the mean values.
      In the case of interwave latencies, the diabetic patients were found to have a
      significant qualitative difference of intervals I-III and I-V on both ears in the
      sense of internal distribution of response. In cases of sensorineural hearing
      loss we found a significant connection with prolonged latencies of I wave on the
      right ear and of I and V waves on the left ear. In all probability, the cause of
      these results could be found in distinctive individuality of the organism
      reactions to the consequences of this disease (disturbance in the distal part of
      N. cochlearis). CONCLUSION: The results of research have shown the existence of a
      significant sensorineural hearing loss in the patients with diabetes mellitus
      type 1 in accordance to the disease duration. We also found qualitative changes
      of brainstem auditory evoked potentials in the diabetic patients in comparison to
      the controls as well as significant quantitative changes in regard to the
      presence of sensorineural hearing loss of the patients.

PMID- 21186542
TI  - [General calculating model of the needs for allogenic stem cell transplantation
      for the patients with leukaemia and myelodysplastic syndrome in Vojvodina].
AB  - INTRODUCTION: Allogeneic stem cell transplantation (SCT) application represents a
      treatment of choice that enables the eradication of malignant clone and chance
      for remedy of the patients with hematological diseases. Only 30-40% of the
      potential patients for allogeneic SCT have an HLA identical sibling, due to the
      fact that families in most of the developed countries are relatively small.
      MATERIAL AND METHODS: This study gives a general model for calculating the needs
      for allogeneic SCT which, enables calculation of the needs for allogeneic SCT per
      1 million inhabitants of Vojvodina on basis of number of potential patients who
      could be treated by allogeneic SCT The number of beds required for transplanted
      patients, and of days in hospital per year as well as the estimation of financial
      aspect of allogeneic SCT have been calculated by means of the cummulative risk
      method, considering the following parameters: the relative number of patients
      suffering from ANLL, ALL, CML, CLL and MDS, 45 and 55-year-old and younger, total
      incidence/ 100,000 inhabitants for each investigated disease and the average
      number of days in hospital of transplanted patients. RESULTS: Total annual needs
      for allogeneic SCT for the patients suffering from ANLL, ALL, CML, CLL and MDS
      together, in transplantation with stem cells from their related donors are 786
      days, from the unrelated donors are 306 days, while for nonmyeloablative
      transplantation with stem cells from their related donors are 558 days and from
      the unrelated ones are 297 days. CONCLUSION: The general calculating model of the
      needs for allogeneic SCT could be used as a basis for planning a regional bone
      marrow donor registry and for creating a similar calculating model of the needs
      for allogeneic SCT in other diseases treatable by HSCT.

PMID- 21186543
TI  - [Causes of blindness in the Republic of Srpska].
AB  - INTRODUCTION: To determine the prevalence and identify potentially curable causes
      of blindness. MATERIAL AND METHODS: We analyzed causes of blindness in 808 blind
      persons, aged from O to 75 years. We classified our findings in 13 categories.
      RESULTS: The least number of blind persons was discovered in children aged from 0
      to 15 years (2.4%), as well as in teenagers (3.4%). The number of blind persons
      in working population, aged from 30 to 60 was (33.1%) and in older population it
      was (60.7%). Glaucoma was the highest cause of blindness (15.90%). Complications
      of myopia (14.6%) took the second place. CONCLUSION: We think that our community
      needs more screening projects for glaucoma, refraction anomalies in children and
      diabetic retinopathy, through which the causes of blindness would be discovered
      and treated on time and people would be much more educated about risks and
      consequences of untreated eye diseases and conditions.

PMID- 21186544
TI  - [Analysis of interjaw ratios in relation to permanent tooth size in subjects with
      class I malocclusion].
AB  - INTRODUCTION: A certain ratio of maxillary to mandibular tooth size is very
      important for the proper occlusion formation. In regular occlusion, the teeth
      must be proportional to size. A discrepancy in tooth size between the mandibular
      and maxillary arch is usually the cause of disharmonious occlusion ratios. One of
      the most widespread methods in determining of discrepancy in tooth size between
      the upper and lower jaw is the Bolton analysis of mesiodistal width of permanent
      teeth. MATERIAL AND METHODS: The subjects of both sexes with the permanent
      dentition and occlusive ratio of Angle Class I classification had had the precise
      impressions taken on the basis of which the study models were obtained. 60
      patients were selected for this investigation (30 males and 30 females) according
      to the following criteria: the presence of completely erupted teeth of permanent
      dentition from the first molar on one side to the first molar on the other side
      of the dental string; good quality of the study models; the absence of
      mesiodistal and occlusive abrasion, caries lesions, Class II fillings; the
      absence of prosthetic or composite restoration;the absence of anomalies in regard
      to shapes, structures and tooth development. We measured the mesiodistal width of
      each tooth from the first molar on one side to the first molar on the other side,
      from the mesial contact point to the distal contact point with the greatest
      interproximal distance. RESULTS: The obtained results for mesiodistal tooth width
      of the right and left side do not show statistically significant differences. The
      mean values of the Bolton anterior ratio showed neither the sexual dimorphism nor
      did the mean values of the Bolton total ratio show any differences in sexes. The
      mean values of the Bolton anterior ratio in our examinees of both sexes are
      significantly higher compared to the values of Bolton norms. The mean values of
      the Bolton total ratios in our examinees of both sexes were not statistically
      different compared to the values of Bolton norms. CONCLUSION: Determining of
      intermaxillary ratios is an important diagnostic and prognostic value in
      orthodontics since it offers a possibility to predict the outcome of orthodontic
      therapy applied on persons with tooth size discrepancy related to the upper and
      lower jaw.

PMID- 21186545
TI  - [Pharmacokinetic modelling of valproate in epileptic patients].
AB  - INTRODUCTION: The aim of our study was to develop and use a population
      pharmacokinetic model for assessment of individual valproate clearance in
      children and young adults suffering from epilepsy. MATERIAL AND METHODS: The
      analysis was performed using 52 steady-state concentrations of valproate
      collected from 26 epileptic patients during the routine clinical practice in our
      hospital. The mean values of age and total body weight were 19.92 years and 57.12
      kg, respectively. NONMEM software with ADVAN 1 subroutine was used for model
      building and assessing the influence of different covariates. A validation set of
      20 epileptic patients (one blood sample per a patient) was used to estimate
      predicted performances of the pharmacokinetic model. RESULTS: The typical mean
      value of the clearance of valproate estimated by the base model in our population
      was 0.3 77 I/h. Out of five considered covariates (total body weight, age, total
      daily dose, gender and polytherapy) only the age of the patients was a
      significant determinant of the clearance of valproate. The final regression model
      for the clearance of valproate was as following: CL (l/h) = 0.223 + 0.00819 * AGE
      CONCLUSION: The derived pharmacokinetical model describes the clearance of
      valproate in relation to patient's age in the observed population. it will help
      to improve the seizure control in young patients with epilepsy in Serbian
      population.

PMID- 21186546
TI  - [Morphology of neurons of human subiculum proper].
AB  - Subiculum proper is an archicortical structure of the subicular complex and
      presents the place of origin of great majority of axons of the whole hippocampal
      formation. In contrast to the hippocampus which has been intensively studied, the
      data about human subiculum proper are quite scarce. The aim of our study was to
      identify morphological characteristics of neurons of the human subiculum proper.
      The study was performed on 10 brains of both genders by using Golgi impregnation
      and Nissl staining. The subiculum has three layers: molecular, pyramidal and
      polymorphic layer. The dominant cell type in the pyramidal layer was the
      pyramidal neurons, which had pyramidal shaped soma, multiple basal dendrites and
      one apical dendrite. The nonpyramidal cells were scattered among the pyramidal
      cells of the pyramidal layer. The nonpyramidal cells were classified on:
      multipolar, bipolar and neurons with triangular-shaped soma. The neurons of the
      molecular layer of the human subiculum were divided into groups: bipolar and
      multipolar neurons. The most numerous cells of the polymorphic layer were bipolar
      and multipolar neurons.

PMID- 21186547
TI  - [Parameters for assessing the severity of clinical presentation of hemorrhagic
      fever with kidney syndrome].
AB  - INTRODUCTION: Hemorrhagic fever with kidney syndrome is an acute infectious
      disease of the zoonotic character, which is characterized by the sudden
      beginning, high temperature, distinct hemorrhagic syndrome and symptoms and signs
      of the acute kidney insufficiency. Hemorrhagic fever with kidney syndrome can
      have mild, moderate and severe clinical picture and the mortality ranges from 5% 
      15% in our area. The purpose of this study was to try to present criteria on the
      basis of which it would be possible to forsee, on time, the severity of the
      clinical picture and to recognize the patient with the most severe disease form.
      MATERIAL AND METHODS: Within the period often years, 87 patients became ill of
      hemorrhagic fever with kidney syndrome and were treated at General Hospital in
      Berane, where they were followed from the aspect of clinical and laboratory
      analyses while the serologic confirmation of the disease was done at the
      Institute of Immunology and Virology "Torlak" in Belgrade. RESULTS: The results
      show that the severity of the clinical picture can be forseen on time on the
      basis of the dynamics of increase of the values of urea and creatinine, duration
      of the shock condition, duration of the oliguria less than 300 ml/24 h, number of
      the collapses, presence of the meningitic syndromes and appearance of the
      asciteses and pleuritic hemorrhage. When, on the basis of these parameters, we
      classify the patients into the categories of mild, moderate and severe clinical
      picture, using the appropriate statistics methods we find out the differences in
      duration of the disease as well as in the result of treatment and number of the
      dialysed patients. CONCLUSION: It is possible to forsee clinical course in a
      patient on time by making timely diagnosis and careful following the clinical and
      laboratory parameters, important for the result of treatment.

PMID- 21186548
TI  - [Evaluation of anesthetic effect of ropivacaine in surgery of chronic periapical
      lessions].
AB  - INTRODUCTION: Ropivacaine is used in orthopedcs, gyneacology, surgery,
      ophtamology, whereas experience about its usage in dentistry is still limited.
      The aim of this research was to compare the anesthetic effect between local
      anesthetics ropivacaine and bupivacaine, in surgical disposals of chronical
      periapical lessions in maxilla. MATERIAL AND METHODS: The study included the
      patients that had indications for surgical removal of chronical periapical
      lessions at one of the frontal teeth of upper jaw. The total total number of
      examinees was 60, and they were devided in two groups. Ropivacaine chloride
      (0.75%) was used as a local anesthetic in one group (Naropin 0.75%; Astra
      Zeneca), and in the other one bupivacaine chloride (0.5%) (Vexelit 0.5%;
      Zdravlje). The authors applied 1.8 ml of block anesthesia for the n.
      infraorbitalis (intra-oral approach) as well as 0.2 ml of the local anesthetic
      from the palatine side for the final branches of N. nasopalatinus in order to
      observe the following anesthetic parameters. (I) Beginning of anesthesia was
      followed by the appearence of upper lip numbness. (II) Pain rating scale
      according to Sisk was used for the objective measurement of the anesthesia
      quality. (III) The pain intensity during the intervention was measured by visual
      analogous scale, on which the patient denoted the intensity of pain he had felt
      during the intervention. (IV) Duration of anesthetic effect--it is followed by
      soft tissues numbness. RESULTS AND DISCUSSION: After the ropivacaine application
      anesthesia effect started in 1.57 min. and after the usage of bupivacaine in 1.67
      min. The mean duration of soft tissue numbness after the application of
      ropivacaine was 321 minutes. Bupivacaine had a shorter anesthetic effect--296.5
      minutes. The quality of anesthesia after the usage of ropivacaine was assessed by
      the surgeons with average mark--1.76. Interventions in which this anesthetic was
      used were performed with minimal pain and without additional anesthesia. The
      quality of anesthesia after the usage of bupivacaine (3.03) was statistically
      much worse (p < 0.01) in comparison to ropivacaine. In visual analogous scale
      where patients denoted the intensity of pain during the intervention with
      ropivacaine the marked average value was 30.1 mm while the average value with
      usage of bupivacaine was 41.7 mm. The patients from the control group, where
      bupivacaine was used, had much stronger pain, statistically significant (p <
      0.05) in comparison to the group where ropivacaine was used. Our results show
      that the quality of anesthesia that was attained with 0.5% bupivacaine was much
      worse than the quality of anesthesia after the application of 0.75% ropivacaine.
      CONCLUSION: Ropivacaine has a potential to replace bupivacaine completely in
      cases when there is the indication for its usage in oral surgery (longlasting
      intervention, interventions followed by intensive postoperational pain, nerve
      blockade).

PMID- 21186549
TI  - [Vertical jump as a tool in assessment of muscular power and anaerobic
      performance].
AB  - Muscular strength and anaerobic power could be assessed by single and multiple
      vertical jump testing procedures. Anaerobic capacity measured by vertical jump
      testing is highly correlative with athletic performance, as compared to other
      anaerobic testing procedures. The most frequently used protocol with contact mat
      or force platform consists of single jump (i.e., squat jump, drop jump,
      countermovement jump) and serial jump testing with different duration. Measured
      variables include jump height and duration along with absolute and relative peak
      muscular power. Several investigators have clearly shown superior jump
      performance variables in elite athletes as compared to non-elite subjects.
      Differences obtained could be due to genetic factors and acute or prolonged
      effects of training regimen. with

PMID- 21186550
TI  - [Venous thromboembolism and oral contraception].
AB  - INTRODUCTION: Because of their safety and efficacy oral contraceptives are
      available without prescription in many countries. Monophasic combined oral
      contraceptives are a combination of estrogen and progestin taken in constant
      amounts. VENOUS THROMBOEMBOLISM: Combined oral contraceptives slightly increase
      the risk of venous thromboemolism, but this event is very rare among non-pregnant
      women of reproductive age. The absolute risk rises with age, obesity, recent
      surgery and certain forms of thrombophilia. The estrogen component of combined
      oral contraceptives increases the synthesis of several coagulation factors in a
      dose-dependent manner. Changes of most of these parameters are very small and
      there is no evidence that they have any effect upon the clinical risk of
      developing venous thrombosis. If a woman has an inherited coagulation disorder
      that increases her risk of developing thrombosis, the risk is increased several
      fold if she ingests estrogen containing oral contraception. CONCLUSION: The
      increased risk of venous thromboembolism associated with combined oral
      contraceptives should have little impact on healthy women, but may have
      substantial impact on women with a history of thromboembolism. Combined oral
      contraceptive use increases the risk of venous thromboembolosm in a dose
      dependent manner. The absolute risk of venous thromboembolism rises with age,
      obesity, recent surgery and certain forms of thrombophilia, as well.

PMID- 21186551
TI  - [Tyrosine kinases in etiopathogenesis and therapy of malignant diseases--C-kit
      activating mutations].
AB  - INTRODUCTION: In the last 15 years, the introduction of molecular biology methods
      and techniques for identifying mutations and measuring gene expression levels of
      mutated genes since recently, have enabled precise molecular diagnostics,
      classification and assessment of prognosis and therapeutic response of malignant
      disease to specific therapies. The increased knowledge of the cancer genome and
      the introduction of multiple new technologies in cancer research have
      significantly improved the drug discovery process, leading to key success in
      targeted cancer therapeutics, including tyrosine kinase inhibitors. Tyrosine
      kinase inhibitors are the molecular targeted neoadjuvant and adjuvant therapy of
      various malignancies. Many more results which are expected from ongoing trials
      are necessary to specify the appropriate dosages, stages at which to start the
      treatment, and which therapeutic combinations to apply.

PMID- 21186552
TI  - [New biohumoral markers of differential diagnosis in patients with suspected
      heart failure].
AB  - INTRODUCTION: In the regular clinic practice, the assessment of the cause of
      dispnea is a dilemma which has a significant implication in both the estimation
      of prognosis and treatment of the patient. In emergency cases, when most
      necessary, it is often very difficult to determine whether dispnea was caused by
      a heart or lung disease. ROLE OF NATRIURETIC PEPTIDE IN PATIENTS WITH DISPNEA: An
      acute patient with dispnea might suffer serious consequences of inadequately
      established diagnosis so congestive heart failure (CHE) has to be diagnosed
      quickly and precisely in the ER. Unfortunately, symptoms and signs of CHF are
      unspecific, it is sometimes impossible to obtain an adequate anamnesis and
      diagnosic procedures currently applied are either insufficiently precise or
      provide scarce information or can not always be performed under appropriate
      conditions. On the basis of previous findings, it has been proved that brain
      natriuretic peptide (BNP) can considerably contribute to the establishment of
      correct diagnosis as well as to the possibility of introducing an adequate
      therapy for those patients. However, the real value of those peptides should be
      estimated in relation to other clinical manifestations and indicators and the
      specifics of examined patients including the age, gender and the presence or
      absence of pulmonary or renal diseases. NATRIURETIC PEPTIDE IN ACCESSEMENT
      GRADIENT OF HEART FAILURE: Determination of natriuretic peptide has represented
      most probably the greatest progress in diagnosing the heart failure since the
      introduction of echocardiography into practice. Its high sensitivity and negative
      predicted value makes it a valid test for excluding congestive heart failure with
      a very high degree of certainty.

PMID- 21186553
TI  - [Prospects of cardioprotection by volatile anesthetics].
AB  - Myocardial ischaemia is followed by some reversibile or ireversibile changes. The
      aim of cardioplegia is to protect numerous intracellular processes: to spare the
      intracellular energy stores, to reduce the free oxygen radicals synthesis, to
      protect the function of the endothelium and myocardial oxygen balance as well as
      ionic balance. The crystalloid or blood cardioplegia, with anterograde or
      retrograde infusion, is a basic procedure of the intraoperative cardiac
      protection. Glucose-insulin-potassium solution was primarily used in a myocardial
      infarction. After the first promising results, some surgical teams started to use
      the high glucose-insulin-potassium solution, as a metabolic modulation approach,
      during a coronary surgery as addition to cardioplegia. During ischaemia, a number
      of intracellular mechanisms deteriorate with bioenergy misbalance and decrease of
      cellular functional reserve. In particular, the regulation of contractility in
      response to loading, alteration in autocrine or paracrine regulation in
      metabolically stressed hearts and acquired, "learned" tolerance of muscle to
      deteriorate perfusion (preconditioning) are examples of a variety of the cardiac
      adaptation. The further improvement in the metabolic modulation during a coronary
      surgery was made with fluorine ion halogenated volatile aneasthetics used for
      anaesthesia. The results of some experimental and first clinical studies induced
      a new approach to the modulation of the intracellular metabolic mechanisms and
      announced a new concept of anaesthetic preconditioning in coronary surgery.
      Large, randomized studies are needed to evaluate anaesthetic preconditioning and
      dependence of its efficiency on type and dose of volatile anaesthetics as well as
      the role of gene regulation in cardioprotection.

PMID- 21186554
TI  - [Investigation of risk factors for acute stress reaction following induced
      abortion].
AB  - INTRODUCTION: Termination of pregnancy-induced abortion is inevitable in family
      planning as the final solution in resolving unwanted pregnancies. It can be the
      cause of major physical and phychological consequences on women's health. Diverse
      opinions on psychological consequences of induced abortion can be found in
      literature. MATERIAL AND METHODS: A prospective study was performed in order to
      predict acute stress disorder (ASD) after the induced abortion and the
      possibility of post-traumatic stress disorder (PTSD). Seven days after the
      induced abortion, 40 women had to fill in: (1) a special questionnaire made for
      this investigation, with questions linked to some risk factors inducing stress,
      (2) Likert's emotional scale and 3. Bryant's acute stress reaction scale.
      RESULTS: After an induced abortion 52.5% women had ASD and 32.5% women had PTSD.
      Women with ASD after the abortion developed more sense of guilt, irritability,
      shame, self-judgement, fear from God and self-hatred. They were less educated,
      had lower income, they were more religious, did not approve of abortion and had
      worse relationship with their partners after the abortion in comparison to women
      without ASD. Age, number of previous abortions and decision to abort did not
      differ between the two groups. DISCUSSION: and conclusion Induced abortion
      represents a predisposing factor for ASD and PTSD in women. Some psycho-social
      factors contribute to the development of stress after abortion. Serbia has a task
      to reduce the number of abortions which is very high, in order, to preserve
      reproductive and phychological health of women.

PMID- 21186555
TI  - [Laparoscopic cholecystectomy of acute cholecystitis].
AB  - INTRODUCTION: Laparoscopic cholecystectomy is a method of choice for surgical
      treatment of diseases of gallbladder. Although most surgeons today use
      laparoscopic cholecystectomy in treatment of severe acute cholecystitis, most
      surgeons still consider acute cholecystitis a relevant contraindication for
      laparoscopic cholecystectomy because of "confused" anatomy and "severe"
      pathology. Aim of the study was to analyze laparoscopic cholecystectomy outcomes
      in treatment of acute cholecystitis. MATERIAL AND METHODS: A prospective analysis
      included 78 patients operated for acute calculose cholecystitis from Jan 2007 to
      Dec 2008. We analyzed clinical characteristics of the course of disease,
      associated diseases, duration of operation, operative and postoperative
      complications, reasons for conversion into open cholecystectomy. RESULTS: The
      study indicated a low percentage of operative and postoperative complications,
      short stay in hospital, quick recovery and saving in treatment. The length of
      preoperative and postoperative hospitalization was 1.4 +/- 0.5 days and 2.5 +/-
      1.6 days, respectively. 25 (32%) patients were operated within 72 hours from the
      onset of symptoms,some operative difficulties were present in 56 (71%) patients,
      light identification of artery and ductus cysticus in 30 (38.50%) patients,
      intraoperative lesion of ductus choledohus in 1 (1.3%); in 6 (7.7%) patients
      conversion into open cholecystectomy was done, the average duration of
      laparascopic cholecystectomy was 58.1 +/- 26.2 min. There were no lethal
      outcomes. CONCLUSION: Laparoscopic cholecystectomy is an efficient and reliable
      operative procedure in treatment of acute cholecystitis. It is much easier to
      select patients for laparoscopic cholecystectomy when preoperative risk factors
      predicting difficulties during the operation are known. An early conversion into
      open cholecystectomy is a rational choice of any surgeon when anatomy is not
      clear and in cases of advanced inflammatory process in order to decrease
      operative and postoperative morbidity.

PMID- 21186556
TI  - [Body mass index in asthmatic children before and after one year inhaled
      glucocorticosteroids therapy BMI].
AB  - INTRODUCTION: Asthma is the most frequent children's disease, with a tendency of
      further growth. Bearing in mind controversial data on obesity of asthmatic
      children and a possible effect of inhaled corticosteroids (ICS) on children's
      growth, the aim of our study was to determine the body mass index (BMI) in
      asthmatic children at the beginning of the therapy and to study the effect of the
      continuous application of ICS on growth and BMI during the period of 1 year.
      MATERIAL AND METHODS: The study included 100 children aged 7 to 18 diagnosed to
      have partly controlled and uncontrolled allergic asthma, who were continuously
      given ICS as a prevention against asthma attacks at Pediatric Clinic of the
      Clinical Center in Kragujevac for the period of 1 year. Children with BMI < p10
      by their age and gender were considered to be underweight, children with p10-84
      as of normal weight, children with p85-97 as overweight and children with BMI >
      p97 as obese. RESULTS: The highest percentage of children with asthma was within
      normal parameters (70%), 10% of the children were underweight (boys: n = 8/60,
      13.3% vs. girls: n = 2/40, 5%), and 18% were overweight/obese. Monovariable
      analysis of variant with repeated measurements have shown a statistically
      significant difference in the height of children in all age groups after a year
      of continuous therapy of ICS (p = 0.000), except in girls aged 15-18, who did not
      show any significant difference in body height after the therapy (p > 0.05).
      CONCLUSION: Asthmatic children with partly controlled and uncontrolled asthma
      have mostly normal BMI and ICS can be safely administered in asthmatic children.

PMID- 21186557
TI  - [Morbidity in newborns exposed to organophosphorus pesticides].
AB  - INTRODUCTION: Insecticides are toxins by which we destroy harmful insects. The
      most frequent insecticides which are used today are organophosphorus pesticides.
      This group of compounds make substances whose activity mechanism is based on the
      inhibition of acetylcholinesterase in nerve synapsis, thus producing holynergic
      syndrome, resulting from the accumulation of acetylcholine which developed due to
      the absence of decomposition under the influence of cholinesterase. In the
      clinical picture of acute toxication by cholinesterase inhibitors there is a
      clear difference between muscarinic and nicotine effects. The basic aim of the
      study was to establish the effects of organophosphorus pesticides present in
      blood and breast milk of mothers on newborns morbidity. MATERIAL AND METHODS: The
      study group consisted of 18 newborns whose mothers had isolated organophosphorus
      pesticides in their blood and breast-milk on the third day after delivery, and
      the control group consisted of 84 newborns whose mothers did not have isolated
      organophosphorus pesticides in their blood and breastmilk. RESULTS: Morbidity is
      three times greater, often in combination with some disorders of the central
      nervous system, and the relative risk for its appearance is eight time greater in
      newborns exposed to organophosphorus pesticides. DISCUSSION: Disorders that
      appear in newborns exposed to pesticides are mutagenic, cancerogenic and
      neurotoxic and some agenses could disturb the immune system which is reflected in
      morbidity increase, primarly of the central nervous system. CONCLUSION: The
      presence of organophosphorus pesticides in blood and breast milk has negative
      effects on newborns. In addition to acetylcholinesterase inhibition,
      organophosphorus pesticides react by means of other mechanisms as well.

PMID- 21186558
TI  - [Progressive course of hypophosphatemic osteomalacia during 25-year follow up].
AB  - INTRODUCTION: Hypophosphatemic osteomalacia is defined as mineralization of the
      newly formed bone matrix (osteoids) in adults as a consequence of the phosphate
      deficiency. CASE REPORT: A female from Belgrade, aged 62 years fell ill in 1982.
      when she was 36. She first felt pains in bones associated with chronic fatigue.
      In 1986. during her hospitalization the presence of neoplastic hematologic,
      endocrinologic, urogenital and gastroenterologic system deseases was excluded.
      Hypophosphatemic osteomalacia was diagnosed on the basis of the history, clinical
      presentation, physical examination, radiologic finding and laboratory analyses
      (lower serum phosphorus level). The initial therapy included a mixture of
      phosphates, vitamin D and calcium. The doses were several times corrected over
      the following four years. In 1990 she had a mild clinical deterioration requiring
      recorrection of the mentioned therapy. In 1993 bilateral femoral neck fractures
      occurred and subsequent osetosynthe as was performed. The disease had a
      progressive character in spite of the administered drug therapy so that multiple
      fractures occurred in 2000. During the last hospitalization in 2008. neither new
      pseudo fractures nor fractures were found although biochemical profile of the
      hypophosphatemic osteomalacia was still present. CONCLUSION: The aim of this
      study was to emphasize the complexity in both diagnostic and therapeutic approach
      in the case of hypophosphatemic osteomalacia. In the presented case the patient
      showed a complicated and progressive course. In our opinion such course was a
      consequence of impossible etiologic treatment and discontinued therapy

PMID- 21186559
TI  - [Cameron lesion: an unusual cause of anemia].
AB  - INTRODUCTION: Cameron lesions are linear gastric ulcers or erosions positioned on
      the crests of mucosal folds at the diaphragmatic impression, in patients with
      large hiatal hernia, and can cause iron deficiency anaemia. CASE REPORT: We
      present a case of a 56-year-old woman who was referred to our institution for
      further investigation after she was examined in gastroenterology emergency room
      (GER) for signs and symptoms of severe hypochromic microcytic anemia without
      signs of acute gastrointestinal bleeding and with no obvious cause of chronic
      blood loss. Endoscopy showed linear ulceration at the level of diaphragm-Cameron
      lesions with large hiated hernia. She was treated with proton pump inhibitors and
      iron supplements. The laparoscopic fundoplication was done. Six months later she
      was asymptomatic. CONCLUSION: Large hiatus hernia may cause iron deficiency
      anemia due to occult bleeding from Cameron erosions. The current therapy concept
      includes the surgical reconstruction of the hiatus together with gastric
      fundoplication in combination with the proton pump inhibitor therapy.

PMID- 21186560
TI  - [GM1 gangliosidosis--case report].
AB  - INTRODUCTION: Gangliosidoses occur due to inherited deficiency of human beta
      galaktosidase, resulting in the accumulation of glicophyngolipides within the
      lisosomes. Clinical manifestations of lysosomal storage disorders are remarkably
      heterogeneous, they can apear at any age and each of them can vary from mild to
      severe conditions. CASE REPORT: We present a patient with an early, infintile
      type of GM, gangliosidosis. The facial features were coarse: hypertelorismus,
      wide nose, depressed nasal bridge with lingual protrusion. From the very first
      months of life she had severe generalized hypotonic, delayed development and
      hapatosplenomegaly. Before she died, when she was 13 months old, she had not had
      any spontaneus movements, she was deaf and blind, dispnoic, with apnoiccrises,
      with anemic face, but without seizures and decerebrate rigidity, which often
      accompanies the terminal stage of this illness. CONCLUSION: The absence of beta
      galaktosidase enzyme activity at the skin fibroblasts confirmed the definitive
      diagnosis. There has been no successful treatment so far, but increasingly better
      results of the gene therapy for other lysosomal storage disorders can make us
      optimistic.

PMID- 21186561
TI  - [Laza K. Lazarevic--doctor, lawyer, writer and warrior in three wars].
AB  - INTRODUCTION: Laza K. Lazarevic was born on the 13th of May, 1851 in Sabac. He
      died on the 11th of January, 1891 in Belgrade. Laza K. Lazarevic was a Serb,
      lawyer, warrior, doctor and writer. He spoke Russian, German and French. Laza
      Lazarevic's road to the title of doctor of medicine. He studied law in Belgrade
      and graduated in 1871 and he graduated from the Faculty of Medicine in Berlin on
      the 28th of January, 1879. He took his doctor's degree in Berlin on the 8th of
      March, 1879 at the same Faculty. His road to the title of doctor of medicine was
      thorny and complicated. LAZA K. LAZAREVIC AS A WARRIOR: He took part in the
      Serbian-Turkish war and the Serbian-Bulgarian war. During the Serbian-Bulgarian
      War (1885) he was first given the rank of reserve medical major and later the
      rank of active medical colonel and then he was appointed assistant chief of the
      Supreme Command of Health Care with the task to establish the Great reserve
      military hospital in Nis. PROFESSIONAL AND SCIENTIFIC WORK OF DR. LAZA K.
      LAZAREVIC: He had seventy two professional and scientific medical papers
      published, a great number of which referring to nervous diseases, such as
      paralysis agitans, sclerosis of medulla spinalis, aphasia and others. Therefore,
      it can be rightly said that Dr. Laza K. Lazarevic was the first Serbian
      neurologist. The very first operation of cataract in Serbia was performed by Dr.
      Laza K. Lazarevic in aseptic conditions, when cocaine was applied for anesthesia.
      He was the first doctor to be sent by the Ministry of Internal Affairs to Vienna
      in 1884 to learn how to prepare animal lymph. In 1879 he was appointed the
      physician of the Belgrade District and in 1881 he was promoted to the position of
      head doctor and Chief of Internal Department of the General State Hospital in
      Belgrade. He was the personal doctor of King Milan Obrenovic. LAZA K. LAZAREVIC
      AS A WRITER: Laza Lazarevic is considered to be the originator of psychological
      stories in Serbian realistic literature and had nine stories published, while
      eight remained unfinished. CONCLUSION: Thanks to his intelligence, hard work,
      determination and persistence and the financial help of Serbia Medical Colonel Dr
      Laza K. Lazarevic gained the best of knowledge across Europe, having studied at
      the most prestigious school in Europe - the fact that can be admired and envied
      even today.

PMID- 21186563
TI  - [Propofol antagonizes the effects of pentylenetetrazole on action potentials or
      synaptic transmission in hippocampal CA1 neurons of rats].

PMID- 21186562
TI  - [Effect of hyperbaric oxygenation treatment on the apoptotic cell death pathway
      after transient focal cerebral ischemia].
AB  - AIM: To evaluate the effects of administration of hyperbaric oxygenation(HBO)
      when initiated at different time after acute transient ischemia. Apoptosis in the
      ischemic penumbra was further investigated to search for the possible mechanism.
      METHODS: The male SD rats were randomly assigned to the following groups:
      control, HBO therapy initiated 3 h after ischemia, HBO therapy initiated 6 h
      after ischemia, HBO therapy initiated 12 h after ischemia. All animals were
      subjected to 90 min intraluminal middle cerebral artery occlusion (MCAO) with the
      regional cerebral blood flow monitored in vivo by laser Doppler flowmetry. HBO
      treatment was performed in a pressure chamber with 100% O2, 3 arm for 1 h.
      Neurological deficits and infarct volumes were assessed at 24 hours after
      ischemia. The immunohistochemical changes of apoptosis in the penumbra were
      evaluated by detecting the expression of cleaved Caspase-3, cleaved Caspase-9,
      Bcl-2, Bax and TUNEL staining. RESULTS: HBO therapy initiated at 3 and 6 hours
      after ischemia significantly improved the neurological function and reduced
      infarct volume. Meanwhile, it increased the expression of Bcl-2 protein and
      decreased the expression of activated Caspase-3, activated Caspase-9 and TUNEL
      positive cells. However, HBO therapy administrated 12 hours after ischemia
      aggravated the neurological deficits and enlarged infarct volume, while it showed
      no significant reduction of apoptotic change compared with control. CONCLUSION:
      There is a therapeutic window for the use of HBO in acute transient cerebral
      ischemia in rats. HBO-treatment is highly effective in reducing infarct volume
      when initiated up to 6h after the onset of ischemia. Inhibition of apoptotic cell
      death in the penumbra appears to be the underlying protective effect of early
      therapy.

PMID- 21186564
TI  - [The effect of time parameters of cerebral ischemic preconditioning on its
      protective effect against global cerebral ischemic injury in rats].
AB  - AIM: To investigate the effects of the duration of cerebral ischemic
      preconditioning(CIP) and interval between CIP and the subsequent ischemic insult
      on the protection of CIP against delayed neuronal death (DND) in the CA1
      hippocampus normally induced by brain ischemic insult. METHODS: Four-vessel
      occlusion cerebral ischemic model of rats (54) was used. The brain of the rats
      was sectioned and stained with thionin to show DND in the CA1 hippocampus.
      RESULTS: No DND was found in the hippocampus of the rats subjected to sham
      operation and CIP, in which 3 min cerebral ischemic preconditioning was
      performed. Obvious destruction of the CA1 hippocampus was found in brain ischemic
      insult group, in which histological (HG) was 2-3 in 6 min and 10 min ischemia
      subgroups and grade 3 in 15 min ischemia subgroup. In CIP + brain ischemic insult
      group, no obvious neuronal damage was found in 3 min-3d-6 min (CIP for 3 min was
      followed by a brain ischemic insult for 6 min at an interval of 3 d, the same as
      the following) and 3 min-3 d-10 min groups, indicating that CIP effectively
      protected neurons of the CA1 hippocampus against DND normally induced by ischemic
      insult for 6 or 10 min. However, in 3 min-1 d-10 min and 3 min-3 d-15 min groups,
      the protective effect of CIP was lower than that in the 3 min-3 d-10 min group.
      The quantitative analysis of the protective effect of CIP on the CA1 hippocampal
      neurons showed that there was no significant difference in protecting number and
      protecting index between 3 min-3 d-6 min and 3 min-3 d-10 min groups (P > 0.05).
      However, the growth index in 3 min-3 d-10 min group was obvious larger than that
      in 3 min-3 d-6 min (P < 0.05). CONCLUSION: Although the protective effects of CIP
      in 3 min-3 d-6 min and 3 min-3 d-10 min groups were similar, the protective
      effect of CIP in 3 min-3 d-10 min group was sensitively found. Maximal protective
      potential of CIP could be induced when using the time parameters of 3 min-3 d-10
      min to establish the model of global cerebral ischemic tolerance.

PMID- 21186565
TI  - [Effects of ventricular arrhythmia during early ischemic myocardium with
      captopril].

PMID- 21186566
TI  - [Effects of shenmai injection on lipid peroxidation in the lung following with
      ischemia/ reperfusion (I/R) injury of limb].
AB  - AIM: To explore the effects of shenmai (Chinese transitional medicine) injection
      on lipid peroxidation in the lung following with ischemia/reperfusion (I/R)
      injury of limb. METHODS: The models of I/R injury of limb were constructed in
      rabbits. Superoxide dismutase (SOD) and malondialdehyde (MDA) in into and out
      flowing pulmonary blood (IPB, OPB) and lung tissue were measured, as well as the
      effects of shenmai injection were observed. RESULTS: Compared with sham group,
      the activity of SOD in IPB, OPB and lung tissue were decreased, and the content
      of MDA was increased after 4 h ischemia followed by 4 h reperfusion. SOD
      increased and MDA decreased significantly by icy shenmai injection 30 min before
      reperfusion. The correlation analysis indicated that MDA was negatively
      correlated with SOD . CONCLUSION: Oxygen free radicals metabolic confusion of
      lung occurred in the course of I/R, shenmai injection can alleviate lipid
      peroxidation, get rid of free radicals and inhibit the damage of lung.

PMID- 21186567
TI  - [The effect of hypoxia-early reoxygenation on persistent sodium current in single
      ventricular myocytes of guinea pig].
AB  - AIM: To investigate the effect of hypoxia/early reoxygenation on persistent
      sodium current (I(Na.P)) in single ventricular myocytes of guinea pig and discuss
      its role and significance during this pathological condition. METHODS: The whole
      cell patch clamp technology was used to record this current and study its change
      under the condition of hypoxia/reoxygenation model. RESULTS: (1) With 0.5 Hz, 1
      Hz and 2 Hz pulse frequency, the current density gap between the first and the
      eighth pulse of I(Na.P) was (0.021 +/- 0.014) pA/ pF, (0.097 +/- 0.014) pA/pF and
      (0.133 +/- 0.024) pA/pF (P < 0.01) respectively. (2) Depolarization with membrane
      holding potential of -150 - -80 mV respectively, I(Na.P) density attenuated
      gradually. (3) The amplitude of I(Na.P) was increased consistently with the
      prolongation of hypoxia time during hypoxia. (4) I(Na.P) was (0.500 +/- 0.125)
      pA/pF, (1.294 +/- 0.321) pA/pF and (0.988 +/- 0.189) pA/pF (P < 0.01, vs
      normoxia, respectively) during normoxia, hypoxia after 15 min and reoxygenation
      after 5 min, respectively. CONCLUSION: These results indicate that I(Na.P) has
      great significance in arrhythmogenesis and calcium-overload, which causes the
      following postischemia and post hypoxia myocardial damage.

PMID- 21186568
TI  - [The protective effects of ginkgo biloba extraction against ischemia/reperfusion
      injury of rat lung].

PMID- 21186569
TI  - [The protect effect of ischemic preconditioning on the gastric mucosal injury
      following ischemia/reperfusion of hind limbs of rats].
AB  - AIM: To observe the degree of gastric mucosal injury following limb
      ischemia/reperfusion (LI/R), and to investigate the mechanism of gastric mucosal
      injury and the protection of ischemic preconditioning (IPC) on gastric mucosal
      injury. METHODS: The model rats which underwent 4 hours of ischemia and 4 hours
      of reperfusion of hind limbs were made. Then we respectively observed and
      determined the histologic lesion score after I/R and IPC + I/R. The gastric
      barrier mucus in mucus were measured in different groups. The values of MPO, SOD,
      MDA and XOD in gastric mucosa and the values of MDA, XOD, SOD, LDH in plasma were
      detected. RESULTS: In the LI/R group, the histologic lesion score increased
      significantly. The content of gastric barrier mucus in mucus decreased
      significantly. The value of MPO, MDA, XOD in gastric mucosa and the values of
      MDA, XOD, LDH in plasma increased remarkably and SOD activity in gastric mucosa
      and in plasma decreased. However in the IPC group, the histologic lesion score
      decreased significantly and the content of gastric barrier mucus in mucus
      increased significantly and the value of MPO MDA XOD LDH in gastric mucosa or in
      plasma decreased remarkably and the SOD activity increased compared to LI/R
      group. CONCLUSION: LI/R will lead to the development of stress ulcer, oxygen free
      radicals play an important role in it. IPC can alleviate the damage of gastric
      mucosa following ischemia/reperfusion of hind limbs. The decrease of OFR is one
      of the protection mechanism of IPC.

PMID- 21186570
TI  - [The effect of ischemic preconditioning on the apoptosis in intestine of rats
      following limb ischemia/reperfusion].

PMID- 21186571
TI  - [Proteomic analysis of hippocampus in the rat].
AB  - AIM: To initially analyze the protein expression in the rat hippocampus with the
      proteomics approach. METHODS: Proteins from hippocampal tissue homogenates of the
      rat were separated by two-dimensional gel electrophoresis(2-DE), and the proteins
      were stained with colloidal coomassie blue to produce a high-resolution map of
      the rat hippocampus proteome. Selected proteins from this map were digested with
      trypsin, and the resulting tryptic peptides were analyzed by matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The
      mass spectrometric data were used to identify the proteins through searches of
      the NCBI protein sequence database. RESULTS: 37 prominent proteins with various
      functional characteristics were identified. The identification of brain protein
      classes, like metabolism enzymes, cytoskeleton proteins, heat shock proteins,
      antioxidant proteins, signalling proteins, proteasome-related proteins, neuron
      specific proteins and glial-associated proteins. Furthermore, 3 hypothetical
      proteins which are unknown proteins, so far only proposed from their nucleic acid
      structure were identified. CONCLUSION: This study provides the first unbiased
      characterization of proteins of the rat hippocampus and will be used for future
      studies of differential protein expression in rat models of neurological
      disorders.

PMID- 21186572
TI  - [Effect of the polypeptide from faliotidae (PFH) on abilities of learning and
      memory in vascular dementia rats].

PMID- 21186573
TI  - [Effects and mechanisms of ginsenoside Rb3 on glutamate excitotoxic injury in
      cultured neurons of rat hippocampus].
AB  - AIM: To observe protective effects of ginsenoside Rb3 on glutamate excitotoxic
      injury in cultured hippocampal neurons and involved mechanisms. METHODS: On
      cultured rat hippocampal neurons treated with glutamate at toxic concentration,
      we made the following investigations: by using MTT assay, LDH leakage detection,
      tests of total NOS, iNOS and cNOS activity, and the protective effects of
      ginsenoside Rb3. RESULTS: Ginsenoside Rb3 can enhance the hippocampal neuronal
      viability, decrease the LDH leakage, elevate the viability of cNOS, and in the
      same time weaken iNOS's viability. CONCLUSION: Ginsenoside Rb3 has the
      significant protective effects on glutamate excitotoxic injury. The involved
      mechanism may include antagonizing the injury of neuron membrane, inhibiting the
      viability of iNOS, and increasing the activity of cNOS.

PMID- 21186574
TI  - [Amelioration of gravimetric technique for measurement of regional brain water
      content].

PMID- 21186575
TI  - [Neuroprotective effects of learning on glutamate-induced neuronal damage in rat
      hippocampus].
AB  - AIM: To investigate the neuroprotective effect of learning on glutamate-induced
      neuronal damage. METHODS: SD rats were intraperitoneally injected with monosodium
      glutamate (MSG) during the period of 3-9 days after born, and were trained to
      find their food by light-dark discrimination at 1 month old or 2 months old. At 3
      months old, all rats were killed and their brains were taken out and cut into
      sections and ultrathin sections. The survival neurons in hippocampus were counted
      under light microscope, and under electric microscope, the ultrastructure, the
      numbers of synapses and the length of synaptic active zone in fields CA1 of
      hippocampus were observed. RESULTS: The survival neurons in field CA3 and CA4,
      the number of synapses and the length of synaptic active zone in field CA1 of
      hippocampus increased in learning group than non-learning group. CONCLUSION:
      These finding indicate that discriminative learning can alleviate neuronal injury
      of hippocampus induced by MSG.

PMID- 21186576
TI  - [Interaction of 5-HT2 and 5-HT3 receptor subtype in 5-HT-induced nociceptive
      responses in peripheral primary sensory nerve ending].
AB  - AIM: To study the correlation between 5-HT-induced pain response and the
      contribution by individual 5-HTR subtypes including 5-HT1R, 5-HT2R and 5-HT3R at
      the level of peripheral primary afferent. METHODS: The experiments were done on
      acutely isolated trigeminal ganglion (TG) neurons using whole-cell patch clamp
      technique and the nociceptive effect was observed on behavior experiments by
      intraplantar injection of test drugs. RESULTS: The majority of cells examined
      responded to 5-HT in a manner of concentration dependence (10(-6) - 10(-3) mol/)
      (61.4%, 54/88) and with a fast activating and rapid desensitizing inward current
      (I(5-HT)), which was thought to be mediated by the activation of 5-HT3R, since it
      could be blocked by 5-HT3R antagonist ICS 205930 and mimicked by 5-HT3R agonist 2
      methyl-5-HT. It was found that I(5-HT) was potentiated by 5-HT2R agonist alpha
      methyl-5-HT markedly, while 5-HT1R agonist R-(+)-UH 301 did not. In behavioral
      experiment performed on conscious rats, intraplantar injection of 5-HT(10(-5),
      10(-4) and 10(-3) mol/L) induced an increment of cumulative lifting time first 20
      min in a manner of concentration dependence. By dissociating 5-HTR subtypes using
      their corresponding antagonists (ICS and CYP) the potency order of hindpaw
      lifting time was identified as follows: 5-HT > 5-HT + ICS > 5-HT + CYP.
      CONCLUSION: The results suggest that in 5-HT-induced nociceptive response at the
      primary sensory level 5-HT3R may play a role of initiation, but 5-HT2R mediates
      maintaining and modulatory effect in the processes of nociceptive information
      convey.

PMID- 21186577
TI  - [The role of AT1 receptor in the changes in TH immunoreactivity of LC induced by
      brain cholinergic stimulation].
AB  - AIM AND METHODS: In the present study, we investigated the TH immunoreactivity
      and the expression of angiotensin AT1 receptor in locus coeruleus after
      intracerebroventricular (i. c. v.) injection of carbachol in conscious SD rats
      with immunohistochemistry. Meanwhile the effects of blocking AT1 receptor were
      also observed. RESULTS: Both mean optical density and number of TH and AT1
      immunoreactive positive neurons were markedly increased in locus coeruleus after
      40 minutes of i.c.v. injection of carbachol (0.5 microg). The enhancement was
      significantly reduced by i. c. v. injection of losartan. CONCLUSION: The results
      above suggest that i. c. v. injection of cholinergic agonist carbachol can
      enhance the activity of adrenergic neurons and the expression of AT1 receptor in
      locus coeruleus. The blockade of AT1 receptor may down regulate the above action
      induced by carbachol in locus coeruleus.

PMID- 21186578
TI  - [Effect of propofol on glutamate, ascorbic acid release in hippocampus during
      global cerebral ischemia/reperfusion in rats].

PMID- 21186579
TI  - [The effects of diazoxide on myocardium function and the expressions of ERK and
      JNK in isolated spontaneous hypertension rat hearts].
AB  - AIM: To investigate the effect of diazoxide preconditioning and the role of ERK
      and JNK in cellular signaling during diazoxide preconditioning protection in
      isolated spontaneous hypertension rat (SHR) hearts. METHODS: Hearts were isolated
      from male SHR rats, and perfused on a Langendorff apparatus. Five groups were
      considered (n = 6). Con: after 40 min perfusion the hearts were submitted to 25
      min ischemia followed by 30 min reperfusion. IP: the hearts were preconditioned
      with 2 periods of 5 min ischemia and 10 min reperfusion prior to 25 min ischemia.
      DP: the hearts were preconditioned with 2 periods of 10 min K-H solution with 50
      micromol x L(-1) diazoxide and 5 min K-H solution reperfusion prior to 25 min
      ischemia. 5-HD: perfuse with 100 micromol x L(-1) 5-HD (a special mitochondrial
      ATP sensitive potassium channel blocker) for 10 min followed by 30 min K-H
      solution perfusion before 25 min ischemia. 5-HD + DP: 100 micromol x L(-1) 5-HD
      was given for 10 min before diazoxide preconditioning. RESULTS: During
      reperfusion, comparing with Con group, the recoveries of left ventricle developed
      pressure (LVDP), + dP/dt(max), - dP/dt(max) and left ventricle end diastolic
      pressure (LVEDP) were improved in IP and DP groups (P < 0.01 vs Con). At the end
      of reperfusion, compared with Con group, the expression of ERK in myocardium were
      higher in IP and DP groups (P < 0.01 vs Con), there was no significance between 5
      HD and Con group, but 5-HD couldn't inhibit the expression of ERK induced by
      diazoxide preconditioning. The expression of JNK in IP and DP groups were
      decreased (P < 0.05 vs Con), this effect could been inhibited by 5-HD.
      CONCLUSION: These results indicated that diazoxide preconditioning could mimic
      ischemic preconditioning, the activation of ERK expression and the declining of
      JNK expression involved in diazoxide preconditioning in isolated SHR hearts.

PMID- 21186580
TI  - [The role of activation of nuclear factor-kappa B on the expression of heme
      oxygenase-1 induced by lipopolysaccharide in rat myocardium].
AB  - AIM: The role of activated nuclear factor-kappa B(NF-kappaB) on the expression of
      heme oxygenase-1 induced by lipopolysaccharide (LPS) in rats' myocardium was
      obversed, and the effect exerted in endotoxic shock was explored. METHODS: The
      changes in mean arterial pressure within 12 hours were recorded on a polygraph.
      The protein expression of NF-kappaB p65 in rats'myocardium, which were induced by
      lipopolysaccharide were measured with immunochemistry. The changes both of
      protein and gene expression of heme oxygenase-1 in rats' myocardium, which were
      induced by injection of LPS or preadministration of the specific inhibitor of NF
      kappaB, pyrrolidine dithiocarbamate(PDTC), were examined by immunochemistry of
      reverse transcripted polymerase chain reaction. RESULTS: (1) LPS caused a rapid
      decrease of MAP within 12 h( P < 0.01). (2) After LPS was administration, the
      protein expression of NF-kappaB p65 in both of micrangium endothelium within
      myocardium markedly increased at 0.5 h and 2 h, while decreased gradually at 6 h
      and 12 h. (3) ES group expressed as migration of acute inflammatory cells and
      dilation and stagnation in blood capillary, while the increase of HO-1 mRNA
      induced by LPS didn't change at the first 0.5 h, began at 2 h, peaked at 6 h, and
      declined at 12 h, respectively. The protein expression of HO-1 in micrangium
      endothelium within myocardium markedly increased and emerged in myocardium, and
      kept a high level at 6 h and 12 h. (4) When a specific inhibitor of NF-kappaB,
      PDTC, was applied to inhibit the level of NF-kappaB, we found that the
      pathomorphological changes of myocardium in ES rats were improved and both HO-1
      mRNA and protein expression in myocardium markedly failed at 6 h. CONCLUSION: NF
      kappaB was activated on the stimulation of LPS, which brought about its
      translocation to the nucleus to act on transcription activity of HO-1 gene. NF
      kappaB might be involved in its signal transductive mechanisms, which might be
      one of the important mechanism of LPS inducing the refractory low arterial
      pressure in ES rats.

PMID- 21186581
TI  - [Adenosine reduces intracellular free calcium concentration in guinea pig
      ventricular myocytes].
AB  - AIM: To observe the effects of adenosine on intracellular calcium concentration
      ([Ca2+]i) level in guinea pig ventricular myocytes and to define the possible
      mechanisms involved. METHODS: The effects of adenosine on [Ca2+]i were
      investigated in guinea pig ventricular myocytes. [Ca2+]i was detected by laser
      confocal microscopy and represented by relative fluorescent intensity ((FI
      FI0)/FI0, %, FIo: control, FI: administration of drugs). RESULTS: (1) Adenosine
      (10, 50, 100 micromol/L) reduced [Ca2+]i of ventricular myocytes in both normal
      Tyrode's solution and Ca(2+) -free Tyrode's solution in a concentration-dependent
      manner. (2) Tyrode's solution containing 30 mmol/L KCl (high K+ Tyrode's
      solution) induced [Ca2+]i elevation in ventricular myocytes, while adenosine (10,
      50, 100 micromol/L) markedly inhibited the increase in [Ca2+]i induced by KCl.
      (3) Pretreatment with DPCPX (1 micromol/L) significantly reduced the effects of
      adenosine (100 micromol/L) in high K+ Tyrode's solution. The effects of adenosine
      (100 micromol/L) on [Ca2+]i in high K+ Tyrode's solution were also partially
      attenuated by pretreatment with L-NAME (1 mmol/L). (4) Adenosine (100 micromol/L)
      markedly inhibited the low concentration of ryanodine-induced [Ca2+]i increase in
      Ca(2+) -free Tyrode's solution. (5) When the propagating waves of elevated
      [Ca2+]i (Ca2+ waves) were produced by increasing extracellular Ca2+ concentration
      from 1 mmol/L to 10 mmol/L, adenosine (100 micromol/L) could block the
      propagating waves of elevated [Ca2+]i, reduce the frequency and duration of
      propagating waves, and reduce [Ca2+]i as well. CONCLUSION: Adenosine may reduce
      the [Ca2+]i in isolated guinea pig ventricular myocytes via inhibiting Ca2+
      influx and alleviating Ca2+ release from sarcoplasmic reticulum(SR). The
      reduction of Ca2+ influx might be due to the inhibition of voltage-dependent Ca2+
      channel via adenosine A1 receptor, and NO might be involved in this process.

PMID- 21186582
TI  - [The establishment of animal models for analyzing heart rate variability in
      conscious rats with hypertension].

PMID- 21186583
TI  - [Delayed electrical uncoupling is involved in kappa-opioid receptor activation 
      induced cardioprotective effect in the isolated rat heart].
AB  - AIM: To determine whether activation of kappa-opioid receptor with U50,488H, a
      selective kappa-opioid receptor agonist, produces any changes in electrical
      uncoupling during prolonged ischemia and whether these changes in electrical
      uncoupling is associated with the cardioprotection induced by kappa-opioid
      receptor activation, and to explore the possible mechanism. METHODS: (1) To
      observe the effect of U50,488H (10(-7), 10(-6), 3 x10(-6) and 10(-5) mol/L), a
      selective kappa-opioid receptor agonist, or with a selective kappa-opioid
      receptor antagonist nor-BNI (5 x 10(-6) mol/L), or with a mitochondrial K(ATP)
      channel inhibitor 5-HD on myocardium during ischemia/reperfusion in isolated
      perfused rat heart. Parameters of measurements include hemodynamic data, formazan
      content, heart rate, coronary flow, and lactate dehydrogenase (LDH). (2) To
      examine the effect of U50,488H of different concentration on electrical coupling
      parameters (including onset of uncoupling, plateau time, slope, and fold increase
      in r1) during 70 min myocardial ischemia in isolated perfused rat heart. RESULTS:
      (1) Pretreatment with U50,488H concentration dependently increased formazan
      content and reduced LDH release induced by 30 min of ischemia and 120 min of
      reperfusion. (2) The onset of electrical uncoupling and plateau time during
      prolonged ischemia was delayed by kappa-opioid receptor activation with U50,488H.
      (3) Linear regression analysis shown that the increase in formazan content and
      decrease in LDH release produced by kappa-opioid receptor activation was
      associated with delayed electrical uncoupling during prolonged ischemia. (4) The
      effects of U50,488H on formazan content, LDH release and on electrical coupling
      were abolished by nor-BNI, or 5-HD. CONCLUSION: This results demonstrate that the
      onset of electrical uncoupling during prolonged ischemia is delayed by kappa
      opioid receptor activation with a selective kappa-opioid receptor agonist
      U50,488H, and that delayed electrical uncoupling is associated with the
      cardioprotection induced by kappa-opioid receptor activation with U50,488H. These
      effects of kappa-opioid receptor activation with U50,488H are mediated by
      mitochondrial K(ATP) channels.

PMID- 21186584
TI  - [The vasoactive material and pulmonary vascular structural remodeling in rats].
AB  - AIM: To investigate the role of vascular endothelial growth factor (VEGF) and
      endothelin-1 (ET-1) on pulmonary vascular structural remodeling in rats and pika.
      METHODS: The Wistar rats which reside at 2 260 m were carried to 3 417 m. After
      they were fed 24 hours,2 weeks and 3 weeks respectively, the level of VEGF and ET
      1 were measured using a kit by ELISA method. Pulmonary tissue was taken out to
      stain with elastica-Van Gieson. The amount of pulmonary arteries (< 100 microm)
      and the component ratio of MA, PMA,and NMA were calculated by using a light
      microscope. The ratio of right ventricle weight to left ventricle plus septum
      weight (RV/LV + S) were measured. RESULTS: The ET-1 was significantly different
      in pika as compared with 24 h, 2 weeks, 3 weeks hypoxic rats (P < 0.01)
      respectively. The levels of VEGF in 2 weeks, 3 weeks rats were much higher than
      that of pika but no difference was found between pika and 24 h hypoxic rats. The
      ratio of MA, PMA obviously increased, and NMA decreased significantly, right
      ventricular hypertrophy was developed in differ groups of hypoxic rats.
      CONCLUSION: The VEGF and ET-1 participate the muscularization of pulmonary
      vessels during hypoxia and play an important role in the process of hypoxic
      pulmonary hypertension in rats, however the VEGF and ET-1 may be maintainable
      only normal organic function in pika.

PMID- 21186585
TI  - [Relationship between expression of STAT3 gene and proliferation of rat pulmonary
      arterial smooth muscle cells under hypoxia conditions].
AB  - AIM: To explore the relationship between expression of signal transduction and
      activators of transcription 3 (STAT3) gene and proliferation of rat pulmonary
      arterial smooth muscle cells (PASMCs) under hypoxia conditions. METHODS: After
      primarily cultured rat PASMCs was treated with AG490 and then exposed to hypoxia,
      the tyrosine-phosphorylated STAT3 protein were detected at 2 h, 6 h, 12 h, 16 h,
      24 h of exposure to hypoxia by semi-quantitive RT-PCR (sqRT-PCR) and Western blot
      respectively. The expression of c-myc mRNA was analyzed by sqRT-PCR. 3H-TdR
      incorporation was used to detect the cell proliferation. RESULTS: The level of
      tyrosine-phosphorylated STAT3 increased at 6 h and peaked at 12 h. The expression
      of c-myc mRNA increased after 2 h of hypoxia and reached maximal level at 4 h,
      then declined at 6 h and to the basal levels at 12 h. With the prolonging of
      hypoxia time, 3H-TdR incorporation in PASMC under hypoxia conditions was
      significantly higher. AG490 inhibited proliferation of PASMCs by preventing STAT3
      tyrosine phosphorylation and the expression of c-myc under hypoxia conditions.
      CONCLUSION: (1) The activation of STAT3 and c-myc gene might play an important
      role in the early stage of hypoxia-induced PASMCs proliferation. (2) STAT3
      upregulated the expression of c-myc during the proliferation of PASMCs induced by
      hypoxia.

PMID- 21186586
TI  - [The inhibitory effect of pethidine on the intestinal muscle and its mechanism].

PMID- 21186587
TI  - [Expression of Urotensin II and its receptor on right ventricle in rats of
      pulmonary hypertension].
AB  - AIM: To observe the expression of Urotensin II (U II) and its receptor (UT) on
      right ventricle in rats with chronic pulmonary hypertension induced by hypoxia
      and hypercapnia. METHODS: Twenty male SD rats were randomly divided into normal
      control group (NC) and hypoxia-hypercapnia 4-week group(HH). Mean pulmonary
      arterial pressure(MPAP) and the weight ratio of right ventricle (RV) to left
      ventricle plus septum (LV+ S) were calculated separately. U II in plasma was
      measured using radioimmunoassay. The expression of U II was observed in right
      ventricle myocytes and right ventricle arteries by immunohistochemistry. The
      expression of U II mRNA and UT mRNA were observed in right ventricle myocytes and
      right ventricle arteries by in situ hybridization. RESULTS: (1) The MPAP and
      RV/LV + S of HH group were higher respectively than those of NC group (P < 0.01,
      respectively). (2) The plasma U II content of HH group did not increased
      obviously than that of NC group. (3) The expression score of U II, U II mRNA, UT
      mRNA by right ventricle myocytes in HH group were higher significantly than those
      of NC group (P < 0.01 respectively). (4) The average value of integral light
      density (LD) of U II, U II mRNA, UT mRNA by right cardial arteries in HH group
      were higher significantly than those of NC group (P < 0.01, respectively).
      CONCLUSION: The expression of U II in right ventricle arteries and right
      ventricle myocytes increase significantly during the formation of pulmonary
      hypertension and right ventricle hypertrophy in rats chronically exposed to
      hypoxia-hypercapnia. These changes indicate that U II might be involved in right
      ventricle remodeling, which promotes proliferation of cardiac muscle cells.

PMID- 21186588
TI  - [Effects of L-arginine and aminoguanidine on the endotoxin induced lung injury in
      rats].
AB  - AIM: To investigate the effects of L-arginine and nitric oxide synthase (NOS)
      inhibitor Aminoguanidine (AG) on endotoxin induced lung injury in rats. METHODS:
      Forty eight healthy male SD rats weighing (300 +/- 20) g were used. The animals
      were anesthetized with 20% urethane 1 g x kg(-1). Common carotid artery (CAA) and
      common carotid vein (CAV) were exposed through a median incision in the neck.
      Mean arterial pressure (MAP) was measured through a pressure transducer connected
      with intubation of CAA. The animals were randomly divided into six groups: group
      1: control: group 2: LPS (5 mg x kg(-1) intravenous injection, i.v.); group 3: AG
      (50 mg x kg(-1) intraperitoneal injection, IP); group 4: high dose L-arginine
      (500 mg x kg(-1), IP); group 5: low dose L-arginine (250 mg x kg(-1) IP). Group
      6: L-arginine + AG (250 mg x kg(-1), 50 mg x kg(-1), IP). Group 1: The animals
      were killed 6 h after 0.9% saline solution was given. Group 2: 0.9% saline
      solution was given 3 h after LPS i.v. and the animals were killed 3 h after
      medication. Group 3, 4, 5 and 6: AG, L-arginine and L-arginine+ AG were given 3 h
      after LPS i.v. respectively and the animals were killed 3 h after medication
      respectively. The pulmonary was removed immediately. The pulmonary coefficient
      and water content in pulmonary tissue were calculated (%). The NO content in
      plasma, MDA content and NOS, SOD activity in the pulmonary tissue were measured.
      RESULTS: L-arginine, AG and L-arginine + AG significantly decreased pulmonary
      coefficient and water content in pulmonary tissue and ameliorated endotoxin
      induced lung injury. AG and L-arginine + AG significantly decreased NO content in
      plasma, decreased MDA content and inhibited NOS activity and enhanced SOD
      activity in the pulmonary tissue. CONCLUSION: It may be concluded that L
      arginine, AG and L-arginine + AG have beneficial effects on lung injury induced
      by LPS.

PMID- 21186589
TI  - [Therapeutic effect of zinc sulfate on lung injury during superior mesenteric
      artery occlusion(SMAO) shock].
AB  - AIM: To study preventive and therapeutic effect of zinc sulfate on lung injury
      during superior mesenteric artery occlusion (SMAO) shock and their mechanism of
      action. METHODS: Model of rabbit SMAO shock was made. The effect of zinc sulfate
      on the malondialdehyde (MDA) in erythrocyte membrane and plasma, oxidase (XOD) in
      plasma, superoxide dismutase (SOD) in erythrocyte and MDA, SOD and pulmonary
      surfactant (PS) in lung tissues homogenate were observed. RESULTS: The
      administration of zinc sulfate decreased MDA and XOD, prevented the reduction of
      SOD and PS, and alleviated lung injury. CONCLUSION: It is suggested that lung is
      injured during SMAO shock and zinc sulfate possesses preventive and therapeutic
      effect, through stabilized membrane.

PMID- 21186590
TI  - [Effect of vasonatrin peptide on the Ca2+ activated K+ channels of vascular
      smooth muscle cells isolated from rat mesentery arteries].
AB  - AIM: To investigate effect and mechanism of vasonatrin peptide (VNP) on Ca2+
      activated K+ channels (K(Ca)) of vascular smooth muscle cells (VSMCs) isolated
      from rat mesentery arteries. METHODS: Changes of K(Ca) induced by VNP were
      measured by the means of whole cell recording mode of patch clamp, furthermore
      effects of HS-142-1(0.3 g/L), 8-Br-cGMP and methylene blue (MB) were observed.
      RESULTS: K(Ca) was significantly enhanced by VNP (10(-6) mol/L), which was
      mimicked by 8-Br-cGMP(10(-3) mol/L) and blocked completely by HS-142-1 or MB (2 x
      10(-5) mol/L). CONCLUSION: VNP increases K(Ca) of VSMCs isolated from rat
      mesenteric arteries, by binding with natriuretic peptide guanylate cyclase
      coupled receptors and increasing the intracellular level of cGMP in VSMCs.

PMID- 21186591
TI  - [The effects of bone marrow stromal cells conditioned medium combined with TPO on
      the expansion of mature megakaryocytes and CFU-Meg in vitro].

PMID- 21186592
TI  - [Experimental study of electroacupuncture improving the obstruction of vestibular
      microcirculation in vertebrobasilar insufficiency and the effect on vestibulo
      ocular reflex].
AB  - AIM: To investigate the mechanism of EA improving the obstruction of inner ear
      microcirculation and the effect on the vestibulo-ocular reflex (VOR) by comparing
      the effects of electroacupuncture (EA) with sibelium (flunarizine hydrochloride)
      on vertebrobasilar insufficiency(VBI). METHODS: Injected with sclerosant-775
      injection into the solt tissue on the left side of cervical vertebral transverse
      processes of rabbits to set up the vertebral artery type of cervical spondylosis
      (VCS) models. Electronystagmography (ENG) induced by linear acceleration (LA) and
      horizontal rotation (HR), the transcranial Doppler (TCD), laser Doppler flowmetry
      (LDF) and hemorheology were used to measure changes of the frequencies of
      nystagmus, the hemodynamics in the basilar artery (BA), inner ear blood
      flow(IEBF) and blood viscosity in VBI rabbits. RESULTS: The frequencies of ENG,
      the velocity of blood flow in BA and IEBF decreased obviously, and whole blood
      middle where viscosity, whole blood lower where viscosity and erythrocyte
      distortion index ( EDI) increased significantly in the model group. Sibelium
      could reduce whole blood viscosity and EDI, and increased the systolic phase
      velocity (Vs) of blood flow in BA, but had no effect on diastolic phase velocity
      (Vd) and mean velocity (Vm). EA could not reduce the viscosity of blood and EDI,
      but had more significant effects on improving IEBF and ENG induced by LA than
      those of sibelium,and had the tendency of increasing Vs, Vd and Vm. EA and
      sibelium had no effect on improving ENG induced by HR. CONCLUSION: Inner ear
      microcirculation obstruction caused by VBI can induce dysfunctions of vestibule
      cyst macula and horizontal semicircular canals. EA may depend upon the
      neurohumoral regulation to improve VBI, and ameliorate inner ear blood supply
      obstruction by enhancing mechanism of local adjusting for microcirculation in the
      inner ear to recover vestibular cyst macula irritability for LA chiefly. There
      exist complicated mechanism that EA adjusts blood flow distribution and
      vestibular signal transduction in vestibular organ in VBI model likely, and
      remain to be researched deeply.

PMID- 21186593
TI  - [Cysteamine promotes mammary gland development in non-pregnant dairy goats].

PMID- 21186594
TI  - [Inhibition of 8-OH-DPAT on spontaneous unit discharges of 5-hydroxytryptamine
      inhibitory unit in rat primary somatosensory cortex].
AB  - AIM: To investigate the effect of 5-hydroxytryptamine (5-HT) on spontaneous unit
      discharges of primary somatosensory cortex (SI-SUD) and the role of 5-HT1A
      receptor in 5-HT inhibitory effect on SI-SUD in rat. METHODS: The SI-SUD was
      recorded before and during microiontophoresis of 5-HT and 8-OH-DPAT (the
      selective agonist for 5-HT1A receptor. The changes of mean of interspike interval
      (MISI) of SI-SUD were analysed and handled with the statistics. RESULTS: (1)
      Effects of 5-HT on SI-SUD may be inhibitory (48/96), excitatory (26/96) or non
      responsive (22/96), and the major effect is inhibitory. (2) In 20 of 5-HT
      inhibited units, 17 are also inhibited with microiontophoresis of 8-OH-DPAT, but
      3 have no obvious response to 8-OH-DPAT. CONCLUSION: The major effect of 5-HT on
      SI-SUD is inhibitory. In majority of 5-HT inhibited units, 5-HT1A receptor may be
      existence, which may involve in the inhibition of 5-HT on SI-SUD.

PMID- 21186595
TI  - [The dynamic changes of heme oxygenase-1 mRNA and protein express at subfornical
      organ in rats with experimental allergic encephalomyelitis].
AB  - AIM: To observe the dynamic changes of heme oxygenase-1 (HO-1) mRNA and protein
      express in subfornical organ in rats with experimental allergic encephalomyelitis
      (EAE) to confirm that SFO is one of the sites for blood-bearing signaling
      molecules entering into brain. METHODS: EAE was induced by CFA-GPSCH on Wistar
      rats, we observed the levels of HO-1 mRNA and its protein expression with
      immunohistochemistry and in situ hybridization technology on 1 d, 7 d, 14 d, and
      21 d after EAE induction in SFO of rats. The relationship between HO-1 and
      symptoms of EAE was also investigated. RESULTS: The expression levels of HO-1
      mRNA and its protein expression were very low in the brains of the control group,
      whereas they were enhanced gradually with pathological course in the brain and
      onsets of symptoms, signs of EAE. On 1 d after induction of EAE, positive cells
      of HO-1 mRNA and its protein expression were observed at SFO, but the labeled
      cells were rarely seen in the other brain regions. On 7 d, the positive cells
      increased markedly. On 14 d the levels of HO-1 mRNA and its protein expression in
      the brains reached the peak, the positive cells of HO-1 were mainly located at
      the choroid plexuses and SFO, as well as the regions around "sleeve-like" lesion
      foci, all of which were coincident with the locations of lesions of EAE. The
      changes of incidence, symptom, reduction of the body weight, and pathology
      lesions of EAE in rat brains were the most significant. On 21 d, the levels of HO
      1 mRNA and its protein expression reduced gradually, which was in parallel with
      remitted symptoms of EAE. When a specific inhibitor of HO-1, Snpp9, was applied,
      the symptoms and pathological lesions of EAE in brains were mitigated markedly.
      CONCLUSION: SFO may be one of the earliest sites for blood-bearing signaling
      molecules entering into brain. The dynamic changes of HO-1 mRNA and its protein
      expression are in parallel with the changes of symptoms and pathological lesions
      of EAE in the brains. Application of some inhibitors of HO-1 may be one of
      potential therapeutic methods for prevention and treatment of EAE.

PMID- 21186596
TI  - [Study of chitosan-phospholipid complex on treatment to brain function of AD
      patient].

PMID- 21186597
TI  - [Effect of hypoxic hypercapnia on expression of COX-2 mRNA in pulmonary
      arterioles].
AB  - AIM: To study the effect of chronic hypoxic hypercapnia on expression of COX-2
      mRNA in pulmonary arterioles. METHODS: SD rats were randomly divided into two
      groups: control group and hypoxic hypercapnic group. COX-2 mRNA was observed in
      pulmonary arterioles by the technique of in situ hybridization. RESULTS: mPAP,
      weight ratio of right ventricle (RV) to left ventricle plus septum (LV + S) and
      COX-2 mRNA in pulmonary arterioles were much higher in rats of hypoxic
      hypercapnic group than those of control group. Light microscopy showed that
      vessel smooth muscle cell hypertrophy and vessel cavity straightness were found
      in hypoxic hypercapnic group. CONCLUSION: Changes of expressions of COX-2 mRNA
      may regulate hypoxic hypercapnic pulmonary hypertension.

PMID- 21186598
TI  - [The effect of central histamine H3 receptor on breathing activity of asthmatic
      guinea pigs].
AB  - AIM: To investigate the effect of selective H3 receptor agonist(R)-alpha
      methylhistamine and antagonist thioperamide on the respiratory response in
      asthmatic guinea pigs respectively. METHODS: Anesthesized guinea pigs were
      prepared with a implanted intracerebroventricular (icv) cannula and instrumented
      for the measurement of respiratory rate (RR) and diaphragmatic electric activity
      (DA). Substance P-like immunoreactive (SP-LI) substances in lower respiratory
      tract were detected by immunohistochemical method. Brain histamine contents were
      measured by fluorometric determination. RESULTS: (1) Intravenous injection of
      ovalbumin caused tachypnea and significant decrease in DA magnitude. At the same
      time, SP-LI substances increased in trachea, bronchus and lung. (2)
      Administration of selective H3 receptor agonist (R)-alpha-methylhistamine (5
      microg) icv immediately after i.v. ovalbumin could significantly ameliorate the
      changes in RR and DA induced by ovalbumin. In accordance, SP-LI substances in
      lower respiratory tract markedly decreased at 5 min and 10 min after (R)-alpha
      methylhistamine microinjection. (3) Icv thioperamide (20 microg) caused a
      significant increase in RR and a decrease in DA. (4) Brain histamine contents
      increased in hypothalamus and cortex during asthma. After microinjection of
      thioperamide (20 microg) icv significant increase of histamine contents in
      hypothalamus and cortex was observed. CONCLUSION: Brain histamine H3 receptors
      may be related to asthmatic respiratory responses.

PMID- 21186599
TI  - [Exploitation of a new noninvasive animal's blood pressure measuring apparatus
      and its function characterization].
AB  - AIM: To produce a new, noninvasive, animal's blood pressure measuring apparatus.
      METHODS: By applying the principle similar with the measurement of human blood
      pressure, we developed a software which knowledge property owned by this research
      group and solved the problems of exactly demarcating the measuring spot of
      diastolic pressure. The blood pressure of rabbits was measured by the novel
      noninvasive animal's blood pressure measuring apparatus and the classic surgical
      catheterizing method simultaneously. RESULTS: The novel noninvasive animal's
      blood pressure measuring apparatus was successfully set up. The measured blood
      pressures by this apparatus are very similar (r > 0.9) with the values obtained
      from the classic, surgical catheterizing method, no matter the blood pressures
      are normal, high or low. CONCLUSION: Our new apparatus can be a reliable method
      for noninvasive measurement of the blood pressure of rabbits and rats.

PMID- 21186600
TI  - [Isolation, incubation and differentiation of pancreatic islet-derived progenitor
      cells from newborn SD rats].
AB  - AIM: To isolate, culture pancreatic progenitor cells derived from islets of
      newborn rats, and to observe the effect of GLP-1 (7-36) NH2 on islet progenitor
      differentiation. METHODS: Islets were isolated purified, islet progenitor cells
      were isolated and proliferated in the modified RPMI-1640 medium supplemented with
      20 microg/L bFGF and 20 microg/L EGF, then were differentiated with 20 nmol/L GLP
      1 (7-36) NH2. The properties of islet progenitor cells were identified primarily
      by hybridization in situ, immunocytochemistry, dithizone (DTZ)-staining, and
      radioimmunoassay before and after differentiation. RESULTS: Islet progenitor
      cells did not express PDX-1, insulin and somatostatin, but nestin. After
      differentiation, a portion of cells expressing PDX-1, insulin mRNA, insulin,
      somatostatin, and nestin, islet-like cell clusters (ICCs) were formed, DTZ
      stained cells were in peripheral region of it. Insulin release was markedly
      greater in media harvested after differentiation of 3 weeks. CONCLUSION: A kind
      of progenitor cells exists in pancreatic islet of newborn SD rats, could be
      expanded continuously. GLP-1 (7-36) NH2 could differentiate pancreatic islet
      derived progenitor cells to form ICCs capable of insulin secretion.

PMID- 21186601
TI  - [The cooperation of OS-9 and PHDs in hypoxia-induced pulmonary hypertension of
      rats].
AB  - AIM: To investigate the dynamic expression of hypoxia-inducible factor 1alpha,
      PHDs and OS-9 in pulmonary arteries of rats with hypoxia-induced pulmonary
      hypertension. METHODS: SD rats were randomly divided into 5 groups (n = 8) and
      exposed to hypoxia for 0, 3, 7, 14 or 21 d, respectively. RT-PCR and in situ
      hybridization were used to determine the expression of mRNA. Immunohistochemistry
      and Western blot were used to determine the expression of protein. RESULTS: HIF
      1alpha protein was poorly positive in control, markedly up-regulated after 3 d
      and 7 d of hypoxia (P < 0.05, vs group C), and then declined slightly after 14 d
      and 21 d of hypoxia. HIF-1alpha mRNA increased dramatically after 14 d of hypoxia
      (P < 0.05, vs group C). PHD1, PHD2 mRNA and protein was positive in group C. PHD2
      mRNA and protein were up-regulated after 3 d of hypoxia (P < 0.05, vs group C),
      reaching its peak after 14 d of hypoxia while PHD1 protein declined after 14 d of
      hypoxia (P < 0.05, vs group C) without statistic mRNA changing. PHD3 mRNA and
      protein were detected at low level in control, markedly up-regulated after 3 d of
      hypoxia (P < 0.05, vs group C), and then PHD3 mRNA kept at high level while PHD3
      protein declined after 14 d of hypoxia (P < 0.05, vs 7 d). OS-9 mRNA was
      positively in control, markedly decreased after 3 d of hypoxia (P < 0.05, vs
      group C), reaching its lowest lever after 14 d of hypoxia. Linear correlation
      analysis showed that OS-9 protein was positively correlated with OS-9 mRNA (r =
      0.82, P < 0.01) and HIF-1alpha protein (r = 0.57, P < 0.01). CONCLUSION: HIF
      1alpha, PHDs and OS-9 are all involved in the pathogenesis of hypoxic pulmonary
      hypertension in rats. OS-9 may interact with both HIF-1alpha and PHDs to promote
      PHD-mediated hydroxylation of HIF-1alpha.

PMID- 21186602
TI  - [Effect of caspase-3 activity in brain tissue of rats given postischemic
      treatment induced by focal cereb ischemic reperfusion].

PMID- 21186603
TI  - [Effect of hypoxia on the expressions of intermedin/ adrenomedullin2 in plasma
      and the tissues of heart and lung in rats].
AB  - AIM: To study the effect and significances of two-week hypoxia on the expression
      of intermedin/adrenomedullin2 (IMD/ADM2) in plasma and the tissues of heart and
      lung in rats. METHODS: Twenty male SD rats were randomly divided into normal
      control group and hypoxia group. The concentrations of IMD/ADM2 and
      adrenomedullin (ADM) in plasma, right ventricle and lung tissue were measured by
      radioimmunoassay. RT-PCR was used to detect the mRNA levels of IMD/ADM2 and ADM
      in right ventricle and lung tissue. RESULTS: (1) The mean pulmonary arterial
      pressure (mPAP) and the weight ratio of right ventricle (RV) to left ventricle
      plus septum (LV + S) of hypoxia group were significantly higher than those of
      normal control group (P < 0.01). (2) The concentrations of IMD/ADM2 and ADM in
      plasma were significantly higher in hypoxia group, compared with normal control
      group (P < 0.01). (3) The concentration of ADM in right ventricle and lung tissue
      in hypoxia group was significantly higher than that in normal control group (P <
      0.01), while there was no significant difference in IMD/ADM2 between the two
      groups. (4) The mRNA levels of IMD/ADM2 and ADM in right ventricle and lung
      tissues were significantly up-regulated in hypoxia group (P < 0.05). CONCLUSION:
      The expressions of IMD/ADM2 peptides and gene in plasma, right ventricular and
      pulmonary tissues are different in the early-middle pathological proceeding of
      pulmonary hypertension induced by two-week hypoxia in rats.

PMID- 21186604
TI  - [The study of the migration mechanism of murine flMSCs in ischemic injured
      brain].
AB  - AIM: To investigate the migration mechanism of murine flMSCs in ischemic injured
      brain. METHODS: flMSCs were isolated and cultured in vitro. BALB/c mice were
      adopted to build model of cerebral ischemia. Chemokine receptor mRNA in flMSCs
      and SDF-1alpha (the only ligand for CXCR4) mRNA in injured brains were determined
      by RT-PCR. Expression and distribution of SDF-1alpha protein was detected by
      Western blot and immunohistochemistry. Migration of flMSCs induced by SDF-1alpha
      in vitro was detected by Boyden chamber assay. RESULTS: Murine flMSCs expressed a
      restricted set of chemokine receptors including CR1, CR3, CXCR1, CXCR2, CXCR3,
      CXCR4. Expression of SDF-1alpha mRNA was significantly increased in ischemic
      injured brain compared with those in normal brain (P < 0.01). Protein level of
      SDF-1alpha in ischemic injured brain (12 h: 0.35 +/- 0.05, 24 h: 0.35 +/- 0.05,
      48 h: 0.88 +/- 0.04) was statistically up-regulated compared with those in normal
      brains (0.74 +/- 0.07, P < 0.01). Expression of SDF-1alpha was significantly
      increased in peri-ischemia area such as cerebral cortex and hippocampus 24 h
      after ischemic injury. Expression of SDF-1alpha wasn't detected in contralateral
      hemisphere and normal brain. Migration of flMSCs could be induced by SDF-1alpha
      and blocked by CXCR4 antibody in vitro. CONCLUSION: Interaction between CXCR4 and
      SDF-1alpha is one of the mechanisms in directing murine flMSCs migration in
      ischemic injured brain.

PMID- 21186605
TI  - [The effect of propofol on astrocyte GFAP expression after the focal cerebral
      ischemia].

PMID- 21186607
TI  - [Alterations of highland transients on memory and limb movement abilities].

PMID- 21186606
TI  - [Effects of taurine on TNF-alpha and NF-kappaB expression of liver injury after
      limbs ischemia/reperfusion in rats].
AB  - AIM: To investigate the effect of pretreatment with taurine on liver injury
      changes and the change of tumor necrosis factor alpha and NFkappaB expression
      following rats limbs ischemia/reperfusion. METHODS: The model of limbs
      ischemia/reperfusion injury on rats was adopted in the experiment. Wistar rats
      were randomized into 4 groups (n = 10): Control group, T group, I/R group and TR
      group. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST)
      and MDA in the plasma, MDA, MPO, calcium in liver tissues were measured by
      colorimetric method. The content of TNF-alpha in plasma and liver tissues was
      determined by radioimmunoassay. The morphologic changes were observed with HE
      staining. The expressions of NF-kappaBp65 in liver tissues were tested by immuno
      histochemistry method. RESULTS: It was found that against the control group, the
      test values of ALT, AST, et al. and expressions of TNF-alpha, NF-kappaB increased
      in I/R group and TR group, but values of those in TR group were lower than in I/R
      group. CONCLUSION: Taurine can decrease the levels of TNF-alpha and NF-kappaB. It
      can mitigate the liver injury after limb ischemia/reperfusion injury in rats.

PMID- 21186608
TI  - [Effects of cardioplegia with tetrodotoxin on intracellular sodium overload of
      ischemia/reperfusion cardiomyocytes].
AB  - AIM: To investigate the effects of polarizing cardioplegia solution with sodium
      channel inhibitor tetrodotoxin (TTX) on intracellular free Na+ concentration
      ([Na+]i) in isolated cardiomyocytes of rat. METHODS: Ventricular myocytes with
      beating were isolated from adult rat hearts by enzymatic dissociation, randomly
      created in group base, group STH2 (contrast group of ischemia/reperfusion) and
      group TFX (treated group). Both Group STH2 and group TTX were arrested by St.
      Thomas No. 2 cardioplegia solution and TTX cardioplegia solution respectively,
      the arrest/re-beating cell model imitating MIRI being established, and imaged by
      laser scanning confocal microscopy (LSCM) for measuring [Na+]i of cardiomyocytes
      in different period. The morphology of cardiomyocytes was observed under the
      inverted microscope. RESULTS: [Na+]i of cardiomyocytes in both group TTX and
      group STH2 after re-beating was higher than that in group base (P < 0.01), and
      [Na+]i in group TTX was lower than that in group STH2 (P < 0.01). During arrest,
      the elevation of [Na+]i in group TTX was lower than that in group STH2. During
      arrest, the elevation of [Na+]i in group TTX was lower than that in group STH2.
      Morphologically, after re-beating, the ratio of active cardiomyocytes with normal
      form in group TTX was higher than that in group STH2 (P < 0.01). CONCLUSION:
      Contrast depolarized cardioplegia solution, TTX cardioplegia solution could
      alleviate ischemia reperfusion injury and intracellular Na+ overload of
      cardiomyocytes.

PMID- 21186609
TI  - [The effects of chronic hypoxic hypercapnia on the TLR4 and NFkappaB in
      hippocampus neuron in rats].
AB  - AIM: To study the expression and effect of TLR4 and NFkappaB protein in
      hippocampus neuron in rats exposed to chronic hypoxic hypercapnia. METHODS: The
      disorder of learning-memory in pulmonary hypertension rat model was reproduced by
      chronic hypoxic hypercapnia. Thirty rats were randomly divided into three groups:
      normal control group, hypoxic hypercapnia 2-week and 4-week group. The number of
      apoptosis neurons in hippocampus CA1/3 was counted by TUNEL method. Activity of
      TLR4 and NFkappaB in hippocampus CA1/3 was detected by using SP
      immunocytochemical technique. RESULTS: The expression of TLR4 protein in
      hippocampus CA1/3 in group 2HH( CA1: 0.1275 +/- 0.0242, CA3: 0.1156 +/- 0.0376)
      and 4HH (CA1: 0.1522 +/- 0.0187, CA3: 0.1427 +/- 0.0453) were significantly
      higher than those in the NC group (P < 0.05, P < 0.01). The positive expression
      of NFkappaB were showed in cell nucleus in group 2HH (CA1: 0.1326 +/- 0.0324,
      CA3: 0.1301 +/- 0.0112) and group 4HH (CA1: 0.1612 +/- 0.0428, CA3: 0.1578 +/-
      0.0365), and significantly higher than those in the NC group (P < 0.05, P <
      0.01). The apoptosis of neural cells in hippocampus CA1/3 gradually increased
      with the time of exposure, and reached peak at 4 weeks (P < 0.01 vs NC group).
      CONCLUSION: The activation of TLR4 and NFkappaB may play an important role in the
      apoptosis of hippocampus neural cells in rat exposed to chronic hypoxic
      hypercapnia.

PMID- 21186610
TI  - [Cardioprotection of testosterone in rat hearts subjected to
      ischemia/reperfusion].
AB  - AIM: To investigate the chronic cardioprotection of testosterone against
      ischemia/reperfusion injury and acute effect against H2O2-stress injury. METHODS:
      The vas deferens were ligated bilaterally and the testes removed from male
      Sprague-Dawley rats, and testosterone propionate was supplemented every day.
      Eight weeks after gonadectomy, all the hearts were mounted on a Langendorff
      apparatus to assess the level of lactate dehydrogenase (LDH) in the coronary
      effluent and the infarct size. Isolated adult ventricular myocytes were obtained
      by enzymatic dissociation, in which H2O2-stress injury model was copied. The
      myocyte contraction was determined, and mitochondrial reactive oxygen species
      (ROS) production was measured by loading with fluorescent probe DCFH-DA. RESULTS:
      In gonadectomy model, pretreatment with testosterone propionate significantly
      decreases the LDH release and the infarct size. In the isolated myocytes model,
      testosterone attenuated the decreases of +/- dL/dtmax and dL which produced by
      H2O2-stress, and prevented the production of ROS induced by H2O2-stress. Co
      treatment with atractyloside or 5-HD attenuated the effect of testosterone.
      CONCLUSION: The findings show the chronic cardioprotection of testosterone
      against ischemia/reperfusion injury and acute effect against H2O2-stress injury
      via opening of mitoK(ATP) channel or/and the inhibiting mitochondrial
      permeability transition pore.

PMID- 21186611
TI  - [Effect of safflower injection on pulmonary hypertension in rat during chronic
      hypoxia and hypercapnia].
AB  - AIM: To study the effect of Safflower injection (a compound of Chinese
      Traditional medicine) on pulmonary hypertension in rat during chronic hypoxia and
      hypercapnia. METHODS: Sprague-Dawley rats were randomly divided into normal
      control group (A), hypoxic hypercapnic group (B), hypoxic hypercapnia + Safflower
      injection group (C). The concentration of TXB2 and 6-keto-PGF18 in plasma and in
      lung homogenate were detected by the radioimmunoassay. RESULTS: (1) mPAP, weight
      ratio of right ventricle (RV) to left ventricle plus septum (LV + S) were much
      higher in rats of hypoxic hypercapnic group than those of control group.
      Differences of mCAP among the three groups were not significant. (2) The
      concentration of TXB2 and the ratio of TXB2/6-keto-PGF1a were significantly
      higher in rats of B group than those of A and C group. (3) The results examined
      by light microscopy showed that WA/TA (vessel wall area/total area), SMC (the
      density of medial smooth muscle cell) and PAMT (the thickness of medial smooth
      cell layer) were significantly higher in rats of B group than those of A and C
      group. (4) The results examined by electron microscopy showed proliferation of
      medial smooth muscle cells and collagen fibers of pulmonary arterioles in rats of
      B group, and Safflower injection could reverse the changes mentioned above.
      CONCLUSION: Safflower injection may inhibit hypoxic hypercapnia pulmonary
      hypertension and pulmonary vessel remodeling by decreasing the ratio of TXB2/6
      keto-PGF1a.

PMID- 21186612
TI  - [The regulative effects of polydatin on toll-like receptor 4 signal transduction
      pathway in lung ischemia/reperfusion injury in rabbits].
AB  - AIM: To investigate protective effects of polydatin(PD) during lung
      ischemia/reperfusion in rabbits and its potential mechanisms. METHODS: Rabbit
      lung model of ischemia/reperfusion (I/R) injury was constituted in vivo. Thirty
      rabbits were divided into groups randomly: Control (C), I/R, PD group,
      respectively. Endotoxin (ET) in plasma was analyzed by End-point Chromogenic
      Assay, the expression of Toll-like receptor 4 (TLR4) mRNA, nuclear factor (NF)
      kappaBp65 mRNA, intracellular adhesion molecule-1 (ICAM-1) mRNA were measured by
      RT-PCR, the morphological changes of lung tissue were observed with hematoxylin
      eosin (HE) staining. RESULTS: There was no significant difference in ET
      concentration of plasma between groups (all of P > 0.05). The expression of TLR-4
      mRNA, NF-kappaBp65 mRNA and ICAM-1mRNA in I/R group were significantly increased
      as compared to C group and PD group, while those expressions in PD group were
      evidently higher than those in C group (all of P < 0.01). Light microscope showed
      that the lung pathological injuries in PD group were obviously alleviated as
      compared to I/R group. CONCLUSION: PD might have a protective effect on lung
      ischemia/reperfusion injury by down-regulating TLR4 and NF-kappaB expression,
      then inhibiting the release of mediators of inflammation as ICAM-1.

PMID- 21186614
TI  - [A noninvasive method for measuring electrocardiogram from chick embryos and
      researching changes of their heart rate during the late period of development].

PMID- 21186613
TI  - [The effect of chronic intermittent hypoxia on p38MAPK in cerebral tissues of
      weanling rats].
AB  - AIM: To study the effect of chronic intermittent hypoxia on p38MAPK in partial
      cerebral tissues of weanling rats. METHODS: Randomly, fifty male SD rats (3-week
      old-4-week-old) were divided into five groups: 2-week-CIH group (2IH), 4-week-CIH
      group (4IH), 4-week-recovery group (4F), 2-week-control group (2C) and 4-week
      control group (4C). Intermittent hypoxia model was induced by an intermittent
      hypoxia cabin. The expression of p38MAPK mRNA and the phosphorylation levels of
      p38MAPK (p-p38 protein) in the hippocampus and prefrontal cortex were measured by
      RT-PCR or Western blot respectively. RESULTS: No matter in the hippocampus, or in
      the prefrontal cortex, the expression of p38MAPK mRNA and p-p38 protein in 2IH,
      4IH and 4F groups were respectively higher than 2C and 4C groups (P < 0.05,
      respectively). CONCLUSION: Chronic intermittent hypoxia can activate the p38MAPK
      in partial cerebral tissues of weanling rats.

PMID- 21186615
TI  - [Mitochondrial calcium uniporter participates in remote preconditioning induced
      cardioprotection in rat hearts subjected to ischemia and reperfusion].
AB  - AIM: To investigate whether mitochondrial calcium uniporter participates in the
      cardioprotection of remote preconditioning in rat hearts subjected to ischemia
      and reperfusion in vivo. METHODS: Rat hearts were subjected to 30 min regional
      ischemia (occlusion of left anterior descending artery) and 120 min reperfusion
      in vivo. Remote preconditioning was induced by three cycles of 5 min of right
      femoral artery occlusion followed by 5 min of reperfusion. The mean arterial
      blood pressure, heart rate, infarct size, and lactate dehydrogenase (LDH)
      activity in plasma during reperfusion were measured. RESULTS: Remote
      preconditioning reduced both the infarct size and LDH release during reperfusion.
      Ruthenium red, an inhibitor of mitochondrial calcium uniporter, also decreased
      both the infarct size and LDH release. Administration of spermine, an activator
      of mitochondrial calcium uniporter, canceled the reduction of infarct size and
      LDH release induced by remote preconditioning. CONCLUSION: These results indicate
      that remote preconditioning protects myocardium against ischemia and reperfusion
      injury, that effect may be related to inhibiting mitochondrial calcium uniporter
      opening.

PMID- 21186616
TI  - [A more sensitive method for the evaluation of visceral pain sensitivity in rat].

PMID- 21186617
TI  - [The effects of Sphing-1-phosphate(S1P) on the potassium channel of the
      ventricular myocytes].
AB  - AIM: To study the effect of Sphingosine-1-phosphate on the delayed rectifier
      potassium current (IK) and the inward rectifier potassium current (IK1) of guinea
      pig isolated ventricular myocytes. METHODS: Whole cell patch clamp technique was
      applied to record the delayed rectifier potassium current and the delayed
      rectifier potassium current of guinea pig isolated ventricular myocytes. RESULTS:
      (1) IK of S1P (1.1 micromol/L) decreased from (1.2 +/- 0.26)nA to (0.95 +/-
      0.23)nA. While IK of S1P (2.2 micromol/L) decreased from (1.43 +/- 0.31)nA to
      (1.02 +/- 0.28)nA. There was significant difference compared to control group (P
      < 0.01, n = 6). The IK peak value was decreased from (1.29 +/- 0.26) nA to (1.26
      +/- 0.37)nA at the group of S1P (1.1 micromol/L) plus suramin (200 micromol/L)
      and showed no significant difference compared to control group (P > 0.05, n = 6).
      (2) IK1 of S1P (1.1 micromol/L) decreased from (-8.94 +/- 2.01)nA to (-8.81 =
      1.55)nA. While IK of S1P (2.2 micromol/L) decreased from (-8.86 +/- 1.59)nA to (
      8.55 +/- 1.39)nA. There was no significant difference compared to control group
      (P > 0.05, n = 6). CONCLUSION: S1P inhibits delayed rectifier potassium current
      of ventricular myocyte in guinea pig remarkably, S1P shows no effects on delayed
      rectifier potassium current of ventricular myocyte in guinea pig.

PMID- 21186618
TI  - [Effect of gap junction on the cardioprotection of ischemic postconditioning in
      rat heart].
AB  - AIM: To determine whether the cardioprotection of ischemic postconditioning and
      heptanol in ischemic heart against ischemia/reperfusion (I/R) is mediated by gap
      junction. METHODS: The effect of ischemic postconditioning, heptanol at different
      doses (0.03, 0.06, 0.30, and 0.60 mg/kg) and AAP10 (10 mg/kg) on the intact rat
      heart during 30 min ischemia and 2 h of reperfusion was observed. Ischemic
      postconditioning was achieved by 3 cycles of 10 s reperfusion/10 s regional
      ischemia starting at the beginning of the reperfusion. The infarct size and the
      arrhythmia scores were measured. The effect of ischemic postconditioning,
      heptanol at different doses (0.05, 0.10, 0.50 and 1.00 mmol/L) and AAP10 (1 x 10(
      7)mol/L) on the isolated heart during 30 min ischemia and 2 h of reperfusion was
      observed. Ischemic postconditioning was achieved by 6 cycles of 10 s
      reperfusion/10 s global ischemia starting at the beginning of the reperfusion.
      The arrhythmia scores and conduction velocity of ventricle muscle were measured.
      RESULTS: In the intact rat heart model, ischemic postconditioning and heptanol
      reduced infarct size and arrhythmia scores. In the Langendorff perfused rat heart
      model, ischemic postconditioning and heptanol reduced arrhythmia scores and
      conduction velocity of ventricle muscle. Administration of AAP10, an opener of
      gap junction attenuated the cardioprotection of ischemic postconditioning and
      heptanol. CONCLUSION: The cardioprotection of ischemic postconditioning and
      heptanol may be related to the attenuation of gap junction communication on
      myocardiac ischemia/reperfusion injury.

PMID- 21186619
TI  - [Immunohistochemical studies of estrogen receptor in the heart of Gekko
      swinhonis].
AB  - AIM: To observed the expression of estrogen receptor (ER alpha and ER beta) in
      the heart of Gekko swinhonis. METHODS: The immunohistochemical technique for the
      estrogen receptor was used. RESULTS: The positive ER alpha and beta cells existed
      in cardiac myocytes and fibroblasts of the atria and the ventricles of Gekko
      swinhonis and had no sexual difference. The difference of ER alpha between the
      atria (11.56 +/- 1.67) and ventricles (6.68 +/- 1.88) was observed in both sexes
      (P < 0.01). CONCLUSION: The atria are probably the main target tissue of estrogen
      through ER alpha pathway while some functions of whole heart will be regulated by
      estrogen through ER beta pathway. The sexual differences aren' t related to the
      content of ER. It may be involved in the state of activity and function of ER
      under the physiological conditions.

PMID- 21186620
TI  - [FAK-related non-kinase plasmid transfection inhibited hepatic stellate cells
      proliferation].
AB  - AIM: To observe the effect of FAK-related non-Kinase (FRNK) plasmid on hepatic
      stellate cell (HSC) proliferation stimulated by fibronectin (FN). METHODS: FRNK
      plasmid was transfected into HSC with transient liposomal transfection. The
      proteins of FRNK, FAK and p-FAK(Tyr397) were assayed by Western blotting
      analysis. The proliferation of HSC was evaluated by improved MTT assay, and cell
      cycle pattern was determined by flow cytometry (FCM). RESULTS: (1) The expression
      of FRNK protein increased after FRNK transfected HSC, and it was at 48 h that the
      expression of FRNK protein was the highest (P < 0.01). The protein level of FAK
      was no significant difference between before FRNK plasmid transfection and after
      transfection (P > 0.05). The expression of p-FAK(Tyr397) protein was down
      regulated after FRNK had been transfected in HSC, (P < 0.01). (2) The HSC
      proliferation inhibition rates at 12 h, 24 h and 48 h after FRNK transfection
      were 20.07%, 26.16%, 29.77%, respectively (P < 0.01). (3) Compared with the non
      FRNK plasmid group, the FRNK-transfected HSCs almost arrested in G0/G1 phase
      (71.4 +/- 2.81 vs 48.9 +/- 1.66, P < 0.01). CONCLUSION: After FRNK were
      transfected successfully in HSCs using lipofectamine, the phosphorylation of FAK
      was inhibited. The HSC proliferation was restrained in a time-dependent manner
      and the HSC was arrested in G0/G1 phase.

PMID- 21186621
TI  - [The effects of protooncogene on oocyte maturation mediated by cytokines].
AB  - AIM: The mechanisms of cytokines in regulating oocyte maturation is still little
      known. The present study attempt to investigate whether the protooncogene of c
      erbB2, c-myb are involved in introducing of cytokines to regulate oocyte
      maturation. METHODS: This research used mouse GV stage oocyte culture model in
      vitro and RT-PCR, Western blotting method to explore the effect of EGF, TNFalpha,
      ET-1 and NO on oocyte maturation; to analyze the c-erbB2 mRNA and c-myb mRNA
      expression and the phosphorylation of MAPK and cyclinB1 expression in oocytes
      affected by above cytokines. RESULTS: EGF(10 microg/L) stimulated meiosis of
      oocytes significantly, the level of c-erbB2 mRNA, c-myb mRNA were increased, and
      promoted the phosphorylation of MAPK and cyclinB1 expression; TNFalpha (1
      microg/L) and ET-1 ((10(-1) mol/L) had the results to EGF. Low dose of SNP (10(
      5)mol/L) had no effect on oocyte maturation, but could significantly reverse the
      suppression of dbcAMP on oocyte maturation. CONCLUSION: c-erbB2 and c-myb were
      involved in introducing of cytokines to regulate oocyte maturation, might be the
      middle link in connection of the cytokines with MAPK and MPF in regulation oocyte
      maturation.

PMID- 21186622
TI  - [Effects of SV heat-resisting protein on the microglial cells in MPTP-treated
      mice].

PMID- 21186623
TI  - [Effect of the endogenous catecholamines synthesized by lymphocytes on T cell
      proliferation].
AB  - AIM: To provide further evidence for the synthesis of catecholamines (CAs) in
      lymphocytes and to investigate the effect of the endogenous CAs synthesized by
      lymphocytes on function of the lymphocytes themselves and the receptor mechanisms
      involved in the effect. METHODS: RT-PCR was performed to detect the expression of
      TH mRNA in the lymphocytes from the mesenteric lymph nodes of rats. Different
      concentrations of pargyline, an inhibitor of monoamine oxydase, and antagonists
      of alpha1-, alpha2-, beta1-, and beta2-adrenergic receptor (AR) were added to the
      lymphocyte cultures, and then proliferative response of the lymphocytes to
      mitogen concanavalin A (Con A) were measured via methyl-thiazole-tetrazolium
      (MTT) assay. RESULTS: The lymphocytes could express TH mRNA, and the expression
      of TH mRNA was significantly higher in the Con A-activated lymphocytes than in
      the resting ones. The treatment of pargyline of 10(-6) and 10(-5) mol/L (not 10(
      7) mol/L) notably attenuated Con A-induced lymphocyte proliferation. Beta2-AR
      antagonist ICI118551 (10(-7) and 10(-6) mol/L) completely blocked, but alpha1-AR
      antagonist corynanthine and alpha2-AR antagonist yohimbine (10(-7) and 10(-6)
      mol/L) partly blocked the suppressive effect of pargyline on the Con A-induced
      lymphocyte proliferation. Nevertheless, atenolol, an antagonist of beta1-AR, had
      no blocking effect on pargyline inhibition of lymphocyte proliferation.
      CONCLUSION: Lymphocytes have the ability to synthesize CAs and the ability is
      enhanced in the activated lymphocytes. The endogenous CAs synthesized by
      lymphocytes can inhibit T cell proliferation and the inhibition of T cells by the
      CAs is mediated predominantly by beta2-AR on the lymphocytes.

PMID- 21186624
TI  - [VEGF165-induced angiogenesis by regulating intracellular free Mg2+ in HUVECs].
AB  - AIM: The mechanism of vascular endothelial growth factor165 (VEGF165) on
      intracellular free magnesium ([Mg2+]i) in human umbilical vein endothelial cells
      (HUVECs) was investigated. METHODS: [Mg2+]i in HUVECs loaded with fluorescent
      magnesium indicator mag-fura-2 were quantitatively detected the use of
      intracellular cation measurement system. RESULTS: VEGF165 significantly increased
      [Mg2+]i in the extracellular Mg2+ and this effect could be blocked by
      pretreatment with tyrosine kinase inhibitors (tyrphostin A23 and genistein),
      phosphatidylinositol 3-kinase (PI3K) inhibitors (wortmannin and LY294002) and
      phospholipase Cgamma (PLCgamma) inhibitor (U73122). In contrast, phospholipase
      Cgamma (PLCgamma) inhibitor analog (U73343), mitogen-activated protein kinase
      inhibitors (SB202190 and PD98059) had no effect on the VEGF165-induced [Mg2+]i
      increase. CONCLUSION: The increase of [Mg2+]i by VEGF165 originates from
      intracellular Mg2+ pool through tyrosine kinase/ PI3K/PLCgamma-dependent
      signaling pathways.

PMID- 21186625
TI  - [The expression of matrix metalloproteinase-2,9 on atherosclerosis in
      experimental rats by treatment of 2,3,4',5-tetrahydroxystilbene -2-0-beta-D
      glucoside].
AB  - AIM: To observe the changes of MMP-2, 9 level on atherosclerosis in experimental
      rats by treatment of 2,3,4',5-tetrahydroxystilbene-2-0-beta-D glucoside (TSG) and
      to investigate the mechanism of TSG in stabilizing plaque and anti
      atherosclerosis. METHODS: The atherosclerosis model of rat was made by feeding
      high grease food and injecting VitD3. Sixty male SD rats were randomly divided
      into six groups: control, Simvastatin, model and TSG 120 mg x kg(-1) x d(-1), TSG
      60 mg x kg(-1) x d(-1) and TSG 30 mg x kg(-1) x d(-1). After 12 weeks, several
      aorta were randomly tested, model and TSG 120 mg x kg(-1) x d(-1), TSG 60 mg kg(
      1) x d(-1) and TSG 30 mg x kg(-1) x d(-1). After 12 weeks, several aorta were
      randomly tested, model made was successful when we found plaque. And after six
      weeks treating, the mRNA expressions of MMP-2 and MMP-9 were measured by RT-PCR.
      The activities of MMP-2 and MMP-9 were measured by Western blot. The levels of
      CRP, IL-6 and TNF-alpha in serum were measured in biochemical method. RESULTS:
      Data of the study demonstrated that the level of TNF-alpha, IL-6, CRP, MMP-2 and
      MMP-9 were remarkably decreased by TSG60, 120 mg x kg(-1) x d(-1) groups, which
      showed a dose-dependent effect. CONCLUSION: TSG has the effect of anti
      atherogenic and stabilizing plaque on the experimental rats with atherosclerosis,
      which are induced by the high cholesterol feeding and VitD3 injecting. The effect
      of TSG seems to be closely involved in regulating the expressions of MMP-2 and
      MMP-9, and inhibiting inflammation.

PMID- 21186626
TI  - [Effect of DHEA on lipid metabolism and antioxidant activity in rats].

PMID- 21186627
TI  - [Effects of exercises training on the rats aorta stress and expression of NF
      kappaB and c-Fos].
AB  - AIM: To investigate the effect of different intensity exercise training on the
      rat aorta stress and expression of NF-kappaB and c-Fos. METHODS: We used
      treadmill exercise to establish the rat models of aerobic exercise and fatigue
      exercise, applied immunohistochemistry of SABC to measure the effect of different
      intensity exercise training on expression of NF-kappaB and c-Fos in the VEC and
      VSMC of rat aorta. RESULTS: The change of aorta blood pressure, compared with the
      control group, which had significant increase in both aerobic exercise and
      fatigue exercise (P < 0.05), but there had no remarkable difference between
      inaerobic exercise and fatigue exercise. Compared with the control group, the
      expression of NF-kappaB and c-Fos of VEC and VSMC in aerobic exercise rats
      remarkably reduced, the opening angle increased remarkably (P < 0.05), and the
      expression of NF-kappaB and c-Fos of VEC and VSMC in fatigue exercise rats
      distinguished upregulated (P < 0.05). Compared with the aerobic training group,
      there was distinguished difference in both the expression of NF-kappaB and c-Fos
      of VEC and VSMC and the opening angle of pectoralis aorta in fatigue training
      rats (P < 0.05). This indicated that different intensity training had different
      effect on the expression of NF-kappaB and c-Fos of VEC and VSMC of rat aorta, and
      the increase trend of expression of fatigue training group was more remarkably.
      CONCLUSION: Expression change of NF-kappaB and c-Fos of VEC and VSMC of rat aorta
      was caused by exercise training, and which had a closed relation with the
      exercise intensity. Chronic shear stress of aerobic training made the expression
      of NF-kappaB and c-Fos of VEC and VSMC of aorta distinguished downregulated,
      which had relationship with homeostasis that VEC and VSMC maintained the blood
      vessel function. Fatigue training caused the increase of wall frictional shear
      stress and circumferential stresses, excessive shear stress caused the expression
      of NF-kappaB and c-Fos of VEC and VSMC of aorta significant upregulated, blood
      vessel happened non-unequal growth exists, and resulted in the remodeling of
      structure and function of blood vessel.

PMID- 21186628
TI  - [The effects of the erythromycin on the production of r-glutamylcys
      glutamylcysteine synthetase and glutathione in the bronchial epithelial cell].

PMID- 21186629
TI  - [Effects of exercise on JNK phosphorylation and expression in skeletal muscle of
      rats].
AB  - AIM: To investigate the effects of exercise on JNK phosphorylation, protein and
      gene expression. METHODS: Male rats were randomly divided into control and
      trained groups. The trained rats were submitted to 1 h or 1.5 h of exercise daily
      and had a fragment of their excised gastrocenemius muscle, 24 h or 48 h after the
      last training session. The train lasted for 7 weeks. The changes in the
      expressions of JNK and p-JNK were determined by Western blotting. The expression
      of JNK mRNA was determined by RT-PCR. RESULTS: Glucose tolerance test found that
      blood insulin concentration was decreased with exercise training. Exercise led to
      a marked increase in p-JNK of trained groups 24 hours after exercise in rats that
      exercised for 1 hour per day and 24 and 48 hours after the exercise in those that
      exercised for 1.5 hours per day as compared with controls, and the protein
      expression of JNK significantly increased 24 and 48 hours after the exercise in
      rats that exercised for 1.5 hours per day. JNK mRNA was increased by exercise 1.5
      h/d, 24 h after the last training session. CONCLUSION: Exercise could increase
      muscle responsiveness to insulin, improving the total JNK and p-JNK and mRNA
      expression.

PMID- 21186630
TI  - [Acetylcholine induces hyperpolarization independent of NO-release in guinea pig
      spiral modiolar artery].
AB  - AIM: Acetylcholine(ACh) is a neurotransmitter and a potent vasodilator in many
      vascular beds. ACh hyperpolarizes the smooth muscle cells(SMCs) of arteries
      including the cochlear spiral modiolar artery(SMA) via an endothelium-dependent
      mechanism, but the biochemical and biophysical basis of the hyperpolarization and
      vasodilation remain unclear and controversial. METHODS: Using intracellular
      recording techniques and an in vitro preparation of the SMA, the ionic mechanism
      of the hyperpolarization and a possible role of nitric oxide(NO) were
      investigated. RESULTS: With 5 mmol/L K(+) in the bathing solution and a minimum
      longitudinal tension, ACh (0.1-10 micromol/L) induced a robust hyperpolarization
      in low RP cells but caused a depolarization in the high RP cells. The ACh
      hyperpolarization was fast in onset and offset and the amplitude was
      concentration-dependent(22 and 30 mV by 1 micromol/L and 10 micromol/L ACh,
      respectively, n = 7 ). ACh also hyperpolarized the cells that initially had a
      high resting potential (RP) but were pre-depolarized by Ba(2+) (50-100
      micromol/L). The onset time courses of the hyperpolarization were often slower in
      these cases than those without the presence of Ba(2+) . The ACh-induced
      hyperpolarization was blocked by atropine (0.1- 1 micromol/L, n = 6) or DAMP (50 
      100 nmol/L, n = 6, a selective M3 antagonist) and also by BAPTA-AM (10
      micromol/L, n = 7, a membrane-permeable Ca(2+)-chelator), or charybdotoxin plus
      apamin (50-100 nmol/L, n= 4, Ca(2+) -activated K(+) -channel blockers), but not
      by Nomega-nitro-L-arginine methyl ester (L-NAME, 300 micromol/L, n = 8, an
      inhibitor of NO-synthase), glipizide (10 micromol/L, n = 4, ATP-sensitive K(+) 
      channel blocker) and indomethacin (10 micromol/L, n = 4, cyclo-oxygenase
      inhibitor). CONCLUSION: It is concluded that ACh-induced hyperpolarization in the
      arterial SMCs is primarily due to an activation of calcium-activated potassium
      channels via M3 receptors of endothelial cell and is independent of NO-release in
      the spiral modiolar artery.

PMID- 21186631
TI  - [The inhibitory effects of tamoxifen on glioma cells SHG-44].

PMID- 21186632
TI  - [To explore the mechanisms of neurogenic inflammation and airway
      hyperresponsiveness of rat by inhaled sulfur].
AB  - AIM: To explore the physiopathological mechanisms of airway injury and the effect
      on the airway responsiveness of rat by inhaled sulfur dioxide(SO2). METHODS:
      Sixteen SD male rats were divided randomly into 2 groups (n = 8): the control
      group and SO2 group. The control group was exposed o pure air. SO2 group was
      exposed to SO2 of the content 1.0 mg/(m(3) x h) 6h daily for consecutive 3 d. At
      4th day, we determined the airway responsiveness, collected the bronchoalveolar
      lavage fluid (BALF), plasma and lung tissue. Then we counted the total cellular
      score in BALF, measured the plasma SP content and made the immunohistochemistry
      staining on the lung tissue (HE and SP methods). RESULTS: Compared with the
      control group, the total cellular score in BALF and plasma SP content in SO2
      group's increased significantly ( P < 0.01). HE staining showed there were a
      great deal of inflammatory cells infiltration under the tunica mucosa
      bronchiorum; and SP immunohistochemistry staining indicated there were
      significant changes in numbers of SP-IR positive fibers of SO2group. CONCLUSION:
      Exposure to low concentration of SO2 would injure healthy rat's airway, and
      induce airway hyperresponsiveness, neurogenic inflammation is one of its critical
      pathophysiological mechanisms.

PMID- 21186633
TI  - [Effects of shivering on airway rewarming].
AB  - AIM: To investigate the effects of shivering on airway rewarming. METHODS: The
      hypothermic dog model without shivering was established by immersing an
      anesthetized dog in cold water and administering atracurium to inhibit the dog
      shivering. The model dog respired warm fully humidified (40-45 degrees C, RH
      99.9%) air and room temperature air(19 +/- 1 degrees C, RH 30% - 75%) to rewarm
      each for 2 hours, the priority of different temperature air respired was arranged
      randomly. After rewarming for 4 hours, the relaxed dog breathed warm humidified
      air by positive pressure ventilation in order to restore its spontaneous
      respiratory. Then the dog continued to respire warm humidified air spontaneously
      until the esophageal (Te) and rectal temperature (Tr) of the dog achieved the
      same degrees as the dog was immersed in the water. The metabolic heat production
      was detected by indirect calorimetry during the experiment. RESULTS: (1) When the
      shivering was inhibited, inhaling warm humidified air for 2 hours made the Tr and
      Te of the dogs increase 0.26-0.39 degrees C and 0.44-1.11 degrees C per hour
      respectively, inhaling air at room temperature for 2 hours made Tr and Te of the
      dogs decrease 0.24-0.51 degrees C and 0.58-0.67 degrees C per hour, respectively.
      And the changes in Tr and Te of the dogs were unrelated to the priority of
      inhaling air at different temperature. (2) When the dog with shivering respired
      spontaneously warm humidified air, the rewarming rates of Tr and Te were 2.26
      2.33 degrees C/h and 1.96-2.38 degrees C/h respectively, quicker than those of
      the dogs whose shivering was inhibited. (3) Compared with metabolic heat
      production of the unshivering dog respiring warm humidified air by positive
      pressure ventilation, that of the shivering dog respiring warm humidified air
      spontaneously increased outstandingly, shivering thermogenesis made the rewarming
      rates increased obviously. CONCLUSION: Airway rewarming is a method conducive to
      rewarming of hypothermia. When the body is shivering, the metabolic heat
      production increases obviously, that makes the rewarming rate increase markedly.
      So the shivering must be inhibited in order to eliminate the interference of
      shivering thermogenesis when the effects of airway rewarming are detected.

PMID- 21186634
TI  - [Respiratory syncytial virus infection enhances airway hyperresponsiveness in
      guinea pigs and the underlined mechanism].
AB  - AIM: To study the relation between Respiratory Syncytial Virus infection and
      asthma development by measuring airway responsiveness (AR) and M2R function.
      METHODS: Guinea pigs (n = 34) were randomly divided into 4 groups: Hep-2/NS group
      (group A, n = 9), RSV/NS group (group B, n =9), Hep-2/OVA group (group C, n = 8)
      and RSV/OVA group(group D, n = 8). On day 21 after infection we tested AR and
      M2R. Then counted eosinophils in BALF and observed pathological change. RESULTS:
      Intraairway pressure(IP mmH20) of group B had no significant difference with
      group A(P > 0.01), and the extent of IP decrease also had no difference between
      groups A and B (P > 0. 05), but IP of C group were much higher than group A
      (P<0.05), with extent of IP decrease lower than group A (P < 0.05). And IP of
      group D were higher than group C (P < 0.01), with the extent of IP decrease much
      lower than group C (P < 0.05). CONCLUSION: RSV infection could enhance OVA
      induced M2R dysfunction, then develop AHR.

PMID- 21186635
TI  - [Effects of psychological stress on performances in open-field test of rats and
      tyrosine's modulation].
AB  - AIM: To explore the effects of different doses of tyrosine modulation on
      behavioral performances in open field test of psychological stress rats. METHODS:
      The animal model of psychological stress was developed by restraint stress for 21
      days. Wistar rats were randomly assigned to five groups (n = 10) as follows:
      control group (CT), stress control group (SCT), low, medium and high-doses of
      tyrosine modulation stress groups (SLT, SMT and SIT). The changes of behavioral
      performances were examined by open-field test. Serum levels of cortisol,
      norepinephrine and dopamine were also detected. RESULTS: The levels of serum
      cortisol were all increased obviously in the four stress groups, and their
      bodyweight gainings were diminished. The behavioral performances of SCT rats in
      open-field test were changed significantly in contrast to that of CT rats.
      However, The behavioral performances of SMT and SHT rats were not different from
      that of CT rats. In addition, the serum levels of norepinephrine and dopamine
      were downregulated obviously in SCT and SLT groups, and no differences were
      observed in other groups. CONCLUSION: Psychological stress can impair body
      behavioral performances, and moderate tyrosine modulation may improve these
      abnormal changes. The related mechanisms may be involved with the changes of
      norepinephrine and dopamine.

PMID- 21186636
TI  - [Mechanism of the influence of CCE3 on bone mineral element metabolism in
      ovariectomized rats].
AB  - AIM: To investigate the influence of CCE3 on bone mineral element metabolism and
      relative hormone in ovariectomized rats. METHODS: 24 female SD rats were divided
      randomly into 4 groups (n = 6): (1) Normal control; (2) sham ovariectomy; (3)
      ovariectomy(OVX); (4) OVX + CCE3. RESULTS: (1) Ca, Mg, S, Co, Mn, Zn reduced
      obviously and P increased in the bone of the OVX rats. (2) E2, P, TSH, T4, CT,
      cortisol, GH reduced obviously and IL-6, FSH, LH increased obviously in serum of
      the OVX rats. (3) CCE3 corrected the changes of Ca, Mg, S, Co, Mn, Zn and P in
      bone as well as the changes of E2, P, TSH, T4, CT, cortisol, GH and IL-6, FSH, LH
      in serum of the OVX rats. CONCLUSION: Changes of relative hormone and IL-6
      induced by CCE3 are the important mechanism of the influence of CCE3 on bone
      mineral element metabolism in ovariectomized rats.

PMID- 21186637
TI  - [The effect of TSPG in vivo on transplantation of neural stem cells in treatment
      of Parkinson's disease mouse].
AB  - AIM: To observe the effect for the model of PD and the transplantation of NSCs
      after injection of TSPG into mouse in advance. METHODS: Firstly, we divided the
      mouse into 5 groups. For the group of 1-4, we established the model of PD with
      MPTP. For the group of 5, before the establishment of the model, we injected TSPG
      into mouse in advance for prevention. And then, we evaluated the effect by
      paralysis agitans score standard and praxiology marker. Secondly, we obtained the
      NSCs from the 7-12 week embryo cerebral cortex. Then we transplanted NSCs which
      pretreated by TSPG into the striatum of the 5 groups. After 60 days, we obtained
      the brain section, and detected the TH by ICC to analyse the differentiation
      status of NSCs. RESULTS: The prevention of TSPG could decrease the neural cells
      damage by MPTP, and could protect the nervous system. After we transplanted NSCs
      into the striatum of Parkinson' s disease mouse, we found that for the group of
      5, the paralysis agitans, auto-activity and memory function had the most distinct
      amelioration. And the number of dopaminergic neurons increased most transparently
      in brain section, and the neurons contact was the most enriched with the adjacent
      nervous cells. CONCLUSION: TSPG can decrease the neural cells damage and can
      produce a marked effect in treatment of PD by transplanting NSCs invivo.

PMID- 21186638
TI  - [Preliminary study on the antioxidant and anti-fatigue effect of recombinant
      SOD].

PMID- 21186639
TI  - [Construction and effect identification of MiR RNAi eukaryotic expression vectors
      of prohibitin].
AB  - AIM: To construct the RNAi eukaryotic vector of inhibitory member of the
      prohibitin (PHB-1) gene and observe the interfering effect in HEK293 cell line
      after the vector transfection. METHODS: The specific Mi RNA sequence was designed
      according to the PHB-1 sequence in GenBank, complementary single-strand DNA
      oligonucleotides were designed and synthesized, and annealed the single-stranded
      oligonucleotides to generate a double strands oligonucleotides , cloned the
      oligonucleotides into pcDNATM6.2-GW/EmGFP-MiR-PHB to obtain an entry clone and
      then sequence analysis was performed. The recombinant plasmid was transfected
      into HEK293 cell by liposome. PHB-1 expression was detected by Western blotting.
      RESULTS: The DNA sequence of interest clone to the vector was constructed to
      generate an entry clone and an expression clone successfully, which were proved
      by sequence determination. Western blotting analysis demonstrated that PHB-1 MiR
      RNA expression construction could suppress the expression of PHB-1. CONCLUSION: A
      RNAi eukaryotic vector containing prohibitin gene was successfully constructed.

PMID- 21186640
TI  - [Experimental substantiation of recombinant epidermal growth factor use efficacy
      in the treatment of wounds of mucosal membrane of oral cavity in the
      immunodeficiency].
AB  - In experiment on rats in the immunodeficiency the use of recombinant epidermal
      growth factor was substantiated that let to speed up reparative regeneration at
      concentration 500 ppb/l drinking water.

PMID- 21186641
TI  - [Comparative histomorphological analysis of bone fragments consolidation in
      compression and non-compression mandible osteosynthesis].
AB  - On experimentally produced model of mandible fractures (on 18 rabbits) the
      efficacy of compression osteosynthesis was compared with fixation by usual plates
      (non-compression osteosynthesis). As was shown by histological study and
      morphometrical analysis of tissue structures from the region of experimentally
      isolated in rabbit mandible bone fragments fixed by microdevices for compression
      and non-compression osteosynthesis in cases of compression osteosynthesis if
      compared with non-compression osteosynthesis at the experimental terms of 2, 3
      and 4 months more intensive new formation and secondary rebuilding of bone tissue
      with its compactification in the region of cortical layer happened. Histological
      study and morphometrical analysis of histological pictures showed that reparative
      osteosynthesis processes were activated in cases of compression osteogenesis not
      only in cortical but also in sponge layer that together with contact enforcing of
      the edge of experimentally isolated bone fragment with maternal bone and bone
      splinters fixation strengthening stipulated for integral positive effect in the
      form of bone integrity restoration acceleration. In case of non-compression
      osteosynthesis the processes of reparative bone formation were observed mainly in
      cortical layer region, in sponge layers they were expressed poorly.

PMID- 21186642
TI  - [Experimental study of dental implants with nanostructured non-resorbable coating
      integration into bone tissue].
AB  - In 2 dogs on both sides of mandible premolars were removed. In 3 months after
      dental alveolus healing intraosseous screwdriver dental implants (Konmet, Russia)
      were installed in the place of the removed teeth. Analogous operation was done on
      the contralateral side: the same type of implants were installed but with new
      nanostructured multifunctional biocompatible non-resorbable coating (MBNC) of the
      Ti-Ca-P-C-O-N composition. The animals were taken out of the experiment in 4
      months after implants installation and implant-bone blocks were studied by SEM
      method. According to the SEM-data in the region of the contact of implant-bone
      without new MBNC only fibrous connective tissue was formed. In case when MBNC was
      used the close welding of bone tissue with implant surface was observed that was
      considered as sign of osteointegration.

PMID- 21186643
TI  - [Features of blood's microelement structure of children of Khabarovsk area with
      dentition anomalies].
AB  - The content of microelements in blood corpuscles and in serum of children was
      defined by atomic-absorption method. Deficiency of essential microelements
      (iodine, copper, nickel) was established and the content of selenium and zinc in
      the majority of the surveyed children was raised.

PMID- 21186644
TI  - [HIV-related salivary gland diseases: diagnostics and treatment].
AB  - In the article modern scientific data about etiopathogenesis, prevalence of
      HIV/AIDS-related salivary glands diseases (SGD) were cited. Questions of
      ultrasonic diagnostics, impact of specific antiviral therapy on SGD clinical
      course were considered. Author's result of a clinical case of three-year
      supervision of a HIV-infected patient with chronic parotid sialadenitis from own
      practice was presented.

PMID- 21186645
TI  - [Optimization of parodontitis treatment of patients with tuberculosis].
AB  - For the purpose to determine the clinic-pathogenetic efficacy of Cycloferon
      liniment in the combined therapy of parodontitis of patients with focal
      tuberculosis medical examination and treatment of 40 patients is carried out. It
      is established, that use of liniment Cycloferon in the combined treatment of
      patients with focal tuberculosis allows to accelerate process of normalization of
      lipid peroxidation parameters and antioxidant potential of blood, to decrease
      infection load (Herpes symplex virus I, Candida albicans, Staphylococcus aureus)
      in parodontal recess and evidence of local inflammation with reduction of
      activity of the tumours necrosis factor and interleukin 1beta, that provides
      acceleration of recuperation processes, lowering the frequency of parodontitis
      relapses.

PMID- 21186646
TI  - [Method of capillaroscopy in evaluation of microcirculation status of gingival
      tissues of intact parodontium].
AB  - With the help of method of capillaroscopy there were studied indices of
      microcirculation in intact parodontium. Beside visual estimation of
      microcirculation status there were received following morphometric microvessel
      characteristics: capillary diameters, capillary blood flow velocity, capillary
      network density. Method of capillaroscopy let to disclose constructive
      peculiarities of micro vessels and their distribution in parodontal tissues.

PMID- 21186647
TI  - [Determination of the efficiency of caries treatment by infiltration method from
      in vitro study results].

PMID- 21186648
TI  - [Study of alternating magnetic field influence on rates of rehabilitation of
      patients after dental implantation].
AB  - New way of using alternating magnetic field is described. Basic functional
      description of new treatment and diagnostic offered (patents of RF No75294 and
      75314), which included digital plethysmograph and regulation of angiotonic
      microcirculation channel device. Comparative estimation of clinical and
      functional indiced of regional blood flow of patients in the main group and in
      the control group showed a positive correlation. Expressed influence of
      alternating magnetic field on frequency of oscillations pulse vessels
      microcircution channel and acceleration of leveling disorder of blood circulation
      in tissue after surgical treatment was proved.

PMID- 21186649
TI  - [Elimination of deformation of right side of face and auricle in the patients
      with hemiatrophy. Clinical-psychological aspects].
AB  - Progressive facial hemiatrophy--is a disease characterized by gradual atrophy of
      all tissues of face half--is known not only as independent nosologic form, but as
      a symptom of diseases row first of all scleroderma. Facial symmetry restoration
      in cases of hemiatrophy presents definite difficulties taking into account
      varieties of forms, defect localizations, sharp thinned coverlets, absence of
      subcutaneous fat, atrophy of soft tissues and osseous tissues of face. Depending
      upon deformation zone siloxane compositions of different elasticity/durability
      properties can be used. Presented clinical observation illustrates possibility of
      full value dynamic patient's checkup with the help of psychological tests, that
      let to evaluate some changes in personal and social functioning of ill person and
      also improvement in his life quality in case of receiving satisfactory aesthetic
      result of the fulfilled operations.

PMID- 21186651
TI  - [Direct method of temporary restoration making with the help of 3D-modeling].
AB  - Use of temporary restorations in the process of prosthetic rehabilitation is
      generally accepted practice. Direct method of temporary restoration making as the
      results of computer modeling is offered. The method essence is in translation of
      the results of 3D computer modeling of the dentition into stereolithographic
      model from which later on silicone print (key) is taken; further on it is used
      for making temporary restoration by the direct method. Such method let in advance
      work off form and size of the future permanent restorations with taking into
      account peculiarities of the face and the smile of each patient and receive
      predictable aesthetic result and increase patient's motivation to the treatment.

PMID- 21186650
TI  - [Increase of the treatment efficacy of the slow developing phlegmonas of
      maxillofacial region with the help immunomodulator Polyoxidonium].

PMID- 21186652
TI  - [Investigation of efficiency of antiseptic composition containing silver
      treatment of prosthodontic and orthodontic stomatitis].
AB  - Results of clinical research of local application antiseptic composition
      containing silver for treatment of prosthodontic and orthodontic stomatitis
      (gingivitis, stomatitis, periodontitis, mucositis). The specified antiseptic
      preparation pad estimated efficiency in treatment of the common health condition
      of patients, complaints of patients and the data of clinical observation.

PMID- 21186653
TI  - [Octacalcium phosphate--precursor of biomineralization, novel bone scaffold].
AB  - Review of the literature and our own investigations describes structure,
      synthesis, hydrolysis, participation in biomineralisation of bone and teeth of
      octacalcium phosphate, a new synthetic bone scaffold.

PMID- 21186654
TI  - [Ways of treatment of included dentition defects by low invasive technologies].

PMID- 21186655
TI  - [Tendency in implantologic treatment relief and short screw driver implants use].

PMID- 21186656
TI  - [Safety issues in patients on oral anticoagulants undergoing invasive
      stomatological procedures].

PMID- 21186657
TI  - [Stomatologists and dentists of Udmurtia--participants of the Great Patriotic
      War].

PMID- 21186658
TI  - [Developmental period medicine].

PMID- 21186659
TI  - [Physical development and puberty of Polish 13 year old adolescents in the first
      decade of 21st century. Current status and secular trend of growth and maturation
      in the last 30 years].
AB  - THE AIM OF THE STUDY: 1. Current physical status and selected pubertal features
      were assessed in Polish 13-year old adolescents, in urban and rural areas. 2.
      Dynamics and secular trends of body height, mass and body mass index in 1980-2008
      were analyzed. MATERIAL AND METHODS: The study was conducted in 2008 in
      prospective cohort of 605 children (305 girls and 300 boys), who had been
      observed in the neonatal period, later at age of 3 years and now at age of 13
      years. 49% adolescents were from urban and 51% from rural area. For secular trend
      analyses comparisons of the age and sex-specific means of body height, mass and
      BMI from 2008 with previous data from 1980, 1999 and 2005 in 13-year old were
      carried out. Similar comparison was made concerning average age at menarche by
      using previous probit analysis to determine average age at menarche during the
      last 3 decades. RESULTS: Mean values of anthropometric features in adolescents
      were a little higher in 13-yrs old living in urban than rural area, but were
      statistically insignificant. Two thirds of examined 13-year-old girls already had
      their first period (menarche), statistically more often urban living girls (p =
      0,017). The median age at menarche for entire group of 13-year-old girls
      estimated by means of Kaplan-Meier analysis was 12.77 years. The girls from urban
      areas had their first menses earlier than their rural living peers (12.65 and
      12.88 years, p = 0.01). There were no statistically significant differences in
      urban and rural boys concerning age of appearance of facial hair. There are
      increases of mean height and weight values during the period of 30 years in 13
      year-olds (2.51 cm and 2.2 kg for girls and 5.51 cm and 5.08 kg for boys) and BMI
      0.21 kg/m3 and 0.75 kg/m2 for girls and boys. The average age of menarche was
      almost the same as in Warsaw girls in 1986 and 1996. CONCLUSIONS: 1. The study
      confirmed a reduction of differences in somatic development between 13-years olds
      in rural and urban areas. 2. Difference in mean age at menarche is still
      observed, they show earlier maturation in urban girls (about 2 months earlier
      than in rural girls). 3. Positive secular trend in height in Polish 13-year-olds
      is observed during the last 3 decades. 4. The mean age at menarche in Polish
      girls stabilized at 12.77 years in the last decade.

PMID- 21186660
TI  - [Application of the Polish version of CHQ-PF28 questionnaire in two population
      studies carried out in 2003 and 2008].
AB  - AIM: To conduct a psychometric analysis of the Polish version of the CHQ-PF28
      questionnaire for measuring the health-related quality of life (HRQL) of children
      and adolescents, on the basis of two population studies carried out in 2003 and
      2008. MATERIAL AND METHODS: The CHQ-PF28 questionnaire was completed by parents
      of 1093 adolescents surveyed in 2003 and by parents of 605 adolescents surveyed
      in 2008. The average age of children was similar (13.4 yrs). An exploratory and
      confirmatory factor analysis was carried out on a combined sample from those
      studies. The HRQL profile of adolescents displaying and not displaying health
      problems, was compared. Mean standardized quality of life scores were calculated
      for all 13 partial dimensions and a two summary dimensions of physical and
      psychosocial health where high CHQ score always means better quality of life.
      RESULTS: In the 2003 study, the mean scores of partial scales ranged between
      59.78 (SD = 20.39) for the scale of family coherence and 97.07 (SD = 11.88) for
      the scale of emotional limitations in playing social roles. In the 2008 study,
      mean scores for the same subscales were as follows: 59.17 (SD = 19.50) and 96.17
      (SD = 14,45). It was concluded that parents assessed children's psychosocial
      health as worse than their children's physical health. In girls, higher mean
      scores were noted in the scales of self-esteem and behavioural disorders; in
      boys, higher mean scores were recorded in the scale of pain sensation. The
      reliability of partial scales was measured using alpha-Cronbach, which only for
      four scales was above 0.7. Six items were identified, which severely impair
      psychometric characteristics of the Polish version of the CHQ-PF28. A clear link
      was found between mean CHQ-PF28 indeces and the results of screening tests which
      identify physical and mental health abnormalities, such as the SDQ (Strengths and
      Difficulties Questionnaire), as well as the CSHCN (Children with Special Health
      Care Needs) test. CONCLUSIONS: The Polish version of the CHQ-PF28 questionnaire
      has satisfactory psychometric characteristics. A wider use of the CHQ-PF28 in
      clinical research and population studies in Poland is fully justified. However,
      we would suggest implementing its abbreviated version, excluding items, which may
      affect the reliability and validity of the subscales and of the overall research
      tool.

PMID- 21186661
TI  - [Health-related quality of life in 13-year-old Polish adolescents measured by CHQ
      PF28 questionnaire in relation to family socioeconomic status in the first year
      of life].
AB  - AIM: To evaluate the impact of living conditions in early childhood on the health
      related quality of life (HRQL - Health-related Quality of Life) among 13-year
      olds. MATERIAL AND METHODS: A prospective, three-phase study was carried out on
      the sample of 605 children born in January 1995 and on their parents.
      Standardized HRQL scores obtained from the Polish version of the CHQ-PF28 (Child
      Health Questionnaire Parent Form) questionnaire was used as outcome measure.
      Information on socioeconomic status was derived from: 1) the questionnaire
      completed by the parents in 1998 on living conditions and fulfilment of families'
      material needs during the child's first year of life; 2) the questionnaire
      completed by parents in 2008--parents' education and a subjective evaluation of
      family affluence; 3) the questionnaire completed simultaneously by the child--the
      family affluence scale and a subjective evaluation of family and neighbourhood
      affluence. For all CHQ-PF28 scores, multivariate linear regression models were
      estimated. RESULTS: The mean summary score of psychosocial health increased from
      71.9 to 76.17 (p = 0.029) when comparing children who lived in bad and good
      conditions during the first year of life. When comparing families which were able
      and unable to satisfy their material needs 13 years earlier, poorer HRQL results
      in adolescents were noted in the latter group both in relation to the summary
      scale of physical (81.1 vs 77.9; p = 0.009) and psychosocial health (75.6 vs
      71.0; p < 0.001). In 5 out of 12 multivariate models, fulfilment of families'
      material needs during the first year of children's life proved to be a HRQL
      predictor independently of the current SES. However, those models were related
      only to psychosocial health indices. CONCLUSIONS: Family material status during
      the first year of the child's life has a strong impact on psychosocial health in
      adolescence. This impact remains, even if current social status was taken into
      account. The study has confirmed the need for implementing programmes for
      preventing social inequities in health aimed at families with small children or
      families expecting children.

PMID- 21186662
TI  - [Parenting practices as predictors of mental health of 13 years old adolescents
      with different body mass index].
AB  - AIM: To investigate the relationship between parenting practices and mental
      health of adolescents with different body mass index. METHODS: The investigation
      was conducted in 2008 as part of prospective cohort study of 605 children (305
      girls and 300 boys).They were observed in the neonatal period, at the age of 3
      years and at the age of 13 years. By mail the adolescents received the Short Form
      of the Alabama Parenting Questionnaire (APQ-9) and the General Health
      Questionnaire (GHQ-12). School nurses performed anthropometric measurements:
      weight and height of pupils. In statistical analysis, hierarchical linear
      regression models were assessed for mother and father parenting practices, both
      for the whole group of adolescents and for adolescents in groups stratified by
      the Body Mass Index (BMI). RESULTS: Stepwise linear regression revealed that in
      the total sample, positive parenting (praising and rewarding) by the mother
      explains 5% of variance of adolescents mental health (father's positive parenting
      explains 4%), consequent discipline of mother or father--1%, supervision by the
      mother--0.4%, by the father--2.5%. In the group of overweight adolescents
      positive parenting by the mother explains 13% (in normal weight group--3%) of
      adolescents mental health variance, positive parenting by the father--15% (in
      normal weight group--2%). Supervision by the father explains 7% of overweight
      adolescents mental health (in normal weight group--1.5%). For overweight girls
      the most important predictors of mental health are positive parenting by the both
      parents and father's supervision. CONCLUSIONS: Parenting practices are important
      predictors of adolescents' mental health, especially for overweight youths.
      Positive parenting (praising and rewarding) may play a significant role in
      improving overweight adolescents' mental health.

PMID- 21186663
TI  - [Body perception among determinants of self-rated health in 13-year-old
      adolescents in Poland].
AB  - The objective of the study was to evaluate the impact of body image on the
      subjective health of adolescents, taking into consideration the modifying
      factors. MATERIAL AND METHODS: The data were collected in 2008 as part of a
      postal survey conducted among 605 children born in Poland in January 1995. Self
      reported health was analysed in two categories: 1) excellent or very good health;
      2) good, fair or poor health. Body image was examined using three variables: self
      perception of physical appearance, subjective assessment of body weight and self
      body image according to the Body Image Subscale (BIS) by Orbach and Mikulincer.
      In addition, the impact of twelve other variables was analysed, which were
      related to: socio-demographic characteristics, physical and psychosocial health
      and also social relations. The impact of all the fifteen variables on self-rated
      health was compared using univariate and multivariate logistic regression.
      RESULTS: In the surveyed group, 31.9% of adolescents assessed their health as
      worse than very good, of which 6.3% considered it fair or poor. Gender, place of
      residence and body mass index (BMI) had no impact on health self-assessment. The
      percentage of those who assessed their health as worse than very good, was equal
      to 48.5% in the group which had a very negative attitude towards their body, and
      61.5% in the subgroup which had big reservations about their body image. In the
      multivariate analysis, the strongest predictor variables for worse health self
      assessment were chronic diseases and negative self-body image. The following
      factors, which can protect young people against worse well-being, were included
      in the final model: positive thinking, social support and high physical activity.
      CONCLUSIONS: There exist many factors which influence the self-perceived health
      in early adolescence, and they may not be classified only as physical ailments.
      Body image appears to be a very important factor at that age. High physical
      activity, support from family, peers and neighbours and positive attitude toward
      themselves are important resources for health which affect adolescents' well
      being.

PMID- 21186664
TI  - [Self-assessment of physical appearance by 13-year-olds as one of predictors of
      functioning in school and peer environment].
AB  - THE AIM: To examine the relationship between perception of physical appearance
      and body weight by adolescents and satisfaction with school and the level of
      perception of social acceptance in relationships with peers. MATERIAL AND
      METHODS: The sample study was conducted in adolescents at the age of thirteen
      years participating in the third stage (2008) of the prospective study.
      Comparative analysis of the evaluation of significant differences between the
      groups using chi2 test were performed. The risk of dissatisfaction with the
      school and feeling low level of social acceptance in relationships with peers was
      estimated using multivariate logistic regression analysis. RESULTS: Perceived
      body weight increased significantly only the risk of dissatisfaction with the
      school, when it was treated as the single predictor. In the models taking into
      account two factors (self-assessment of body mass and physical appearance), self
      perception of body mass did not increase significantly the risk of
      dissatisfaction with school or a low sense of social acceptance. The risk of
      dissatisfaction with school was negatively increased in boys (Exp (B) = 11.371, p
      < 0.001) or average (Exp (B) = 2.726, p < 0.01) evaluated their body and in girls
      with negative self-perception of appearance (Exp (B) = 3.267, p < 0.05), compared
      with those who had good self perception of physical appearance. Greater risk of
      experiencing lack of acceptance by peers was observed in girls who assess their
      appearance as average (Exp (B) = 2.194, p < 0.01) and in the group of boys who
      judged their appearance as bad (Exp (B) = 6.548, p < 0.05) compared with those
      who were satisfied with their appearance. CONCLUSIONS: Positive self-perception
      of their appearance determines satisfaction with the school and the feeling of
      acceptance in relationships with peers. In the perception of social acceptance
      from peers, body weight perception is not a significant predictor. It would be
      justified, especially in junior high schools, to conduct educational programmes
      in order to assist students to build positive self-esteem.

PMID- 21186665
TI  - [Meals consumption among thirteen years olds and selected family socio-economic
      correlates].
AB  - AIM: To analyse the influence of selected family socioeconomic factors on the
      regularity of meals consumption among 13-years aged adolescents. MATERIAL AND
      METHOD: Group of 605 13-years olds identified in the prospective cohort study in
      2008 was analysed. Data was gathered with use of posted questionnaires. On the
      basis of information given by children the regularity (4-5 times a week) of meals
      consumption on school days and eating meals with parents were correlated with
      parents' educational level, occupational status and perceived family wealth. The
      study also recognised the distinction between urban and rural residents. RESULTS:
      Most questionnaires were filled out by mothers (95%), only 5% by fathers. In
      urban area, the mother's occupation and the perceived family wealth, correlate
      with children meals consumption and eating meals with parents. Children whose
      mothers have a job eat breakfast 1.5 times and supper 3 times less regularly,
      than children whose mothers don't work. Children from poor families eat breakfast
      14 times less regularly than children from rich families as well as eat supper 3
      times less regularly than children from average wealthy families. In the rural
      area, the regularity of meals consumption significantly influence the mother's
      education. Children whose mothers have a secondary education, compared with
      children of mothers with basic education, are 4 times more likely to eat dinner
      and supper regularly. CONCLUSION: The family socioeconomic factors significantly
      correlate with regularity of 13-years olds meals consumption and regularity of
      family meals. The place of residence involve the different factors influencing
      meals consumption habits. It was shown that children and fathers were too little
      engaged in family life, including family meals preparation and consumption.

PMID- 21186666
TI  - [Determinants of adolescents' physical activity].
AB  - AIM: To compare the study results concerning the correct level of 13- and 15-year
      old adolescents physical activity and impact of selected physical activity
      determinants (self-efficacy, BMI, gender, domicile) obtained from two nationwide
      studies out in Poland, using a similar questionnaire in 2006 and 2008. MATERIAL
      AND METHODS: The material comes from two studies. The first, the 2006 HBSC survey
      included 2287 15-year-old students (1092 boys and 1195 girls); the second, the
      2008 third phase of a prospective, three-phase survey, included 605 13-year-olds
      (300 boys and 305 girls) born in Poland in January 1995. Questions on physical
      activity were analysed (MVPA), along with the following determinants: self
      efficacy, domicile, gender, body weight and height. Cross-tabulation with chi2
      analysis and multilevel modelling were applied. RESULTS: Physical activity
      deficiency was found in both examined populations. In study I--84.8%, in study II
      -80.3%. Self-efficacy (p < 0.01), gender (p < 0.001) and BMI (p < 0.04) had an
      impact on the 15-year-olds physical activity. In 13-year-olds, only self-efficacy
      was close to significant relation with physical activity. The results of
      multilevel logistic regression in study I identified protective factors: male
      gender [OR = 0.41; CI (OR): 0.32-0.53] and strong self-efficacy [OR = 0.66; CI
      (OR): 0.51-0.85]; while being underweight was identified as a risk factor [OR =
      2.77; CI (OR): 1.11-6.95]. In study II only strong self-efficacy was found as a
      protective factor [OR = 0.51; CI (OR): 0.30-0.89] against lack of physical
      activity. CONCLUSIONS: Most of the examined adolescents from study I as well as
      study II suffered from physical activity deficiency. The share of biological
      determinants (gender, BMI) in maintaining correct level of physical activity
      increased with age. A link between physical activity and self-efficacy was
      demonstrated in the 15-year-olds, while this tendency was identified in the 13
      year-olds. The results point to a need for implementing programmes supporting
      self-efficacy in children under the age of 13 and to carry out assessment of self
      satisfaction concerning own bodyweight. In preparing these programmes sex
      differences should be taken into consideration.

PMID- 21186667
TI  - [The author's inflation].

PMID- 21186668
TI  - [Microbiological and epidemiological analysis, and clinical outcome of patients
      with bloodstream infection from an Esquel hospital in the period 2007-200].
AB  - In order to evaluate the bacteremic episodes, the blood cultures performed in 867
      patients during a 29-month period were reviewed. The incidence of significant
      bloodstream infections was 10/1000 admissions/year. About 47% of bacteremias were
      community-acquired (CAB), 22% nosocomial (NB), and 31% health care-associated
      (HCAB). The five most common pathogens were: Streptococcus pneumoniae,
      Staphylococcus aureus, Escherichia coli, Enterococcus spp. and coagulase-negative
      staphylococci, whereas the main sources were: respiratory, intraabdominal and
      unknown. The major organism in CAB was S. pneumoniae, and S. aureus in NB and
      HCAB. The ineffective empirical-antimicrobial-therapy [IEAT (total 26.5%)] was
      much higher in NB and HCAB vs. CAB (p < 0.05). There was no significant
      difference in mortality and IEAT between known vs. unknown sources. Old age (> 70
      yrs), previous antibiotic therapy, hospitalization in clinical medical services,
      Enterococcus spp. and methicillin-resistant Staphylococcus isolates were more
      associated with IEAT (p < 0.05). Previous antibiotic therapy and longer hospital
      stays were more common in NB vs. CAB and HCAB (p < 0.05). Overall and septicemia
      associated mortality was 28.9% and 21.7%, respectively. Univariate associations
      with increased mortality (p < 0.05) included: hypothermia, WBC < 1499/mm3,
      hypotension, presentation with septic-shock, hospital-stay 10 days, and
      polymicrobial bacteremia. The early administration of effective empirical
      antimicrobial therapy according to our epidemiological characteristics and an
      aggressive hemodynamic treatment in presence of septic shock could reduce
      bacteremia-associated morbidity and mortality, costs and length of hospital
      stays.

PMID- 21186669
TI  - [Comparison of diagnostic methods for Clostridium difficile-associated diarrhea].
AB  - In order to compare different methods for the diagnosis of Clostridium difficile
      associated diarrhea, fecal filtrates from patients presenting symptoms compatible
      with this condition, were analyzed. Biological activity on Vero cells (biological
      assay), dot blot with antibodies anti-TcdA and anti-TcdB, and a PCR assay for the
      tcdB gene, were evaluated. Titles of biological assays were > or =64 for 44 out
      of 177 samples. Nineteen samples were positive in both biological and PCR assays.
      The analysis by dot blot using anti-TcdA and anti-TcdB antibodies showed that 46
      samples out of 149 were positive for both toxins whereas 12 samples were only
      positive for TcdB, and 5 samples only positive for TcdA. Discrepancies in the
      different methods could be related to truncated genes, low number of
      microorganisms in the samples and toxin degradation. The results herein presented
      show the need for developing diagnostic approaches compatible with the complex
      epidemiological situation of this clinically relevant intestinal pathogen.

PMID- 21186670
TI  - [Tuberculous peritonitis in HIV-infected patients].
AB  - In order to describe the clinical and laboratory findings of Mycobacterium
      tuberculosis peritonitis M. tuberculosis in HIV+ patients, we conducted a
      retrospective analysis of the medical records of HIV+ patients with isolation of
      M. tuberculosis from ascitic fluid (AF), assisted at Hospital Muniz, Buenos
      Aires, Argentina (1996-2005). RESULTS: 21 patients were included. Median age: 33,
      male sex: 52%; peripheral blood CD4-T lymphocyte count (median): 85/mm3; prior
      history of tuberculosis: 40%; cirrhosis: 65%; enolism: 45%; HCV coinfection: 85%.
      The most frequent symptoms were abdominal distension (71%), fever (62%) and
      abdominal pain (19%). The chemical characteristics of the AF were (median):
      leukocyte count: 751/mm3 (mononuclear predominance: 79%), protein: 3.1 g/dl, LDH:
      351 IU/l. AF samples positive for acid fast bacilli at direct microscopic
      examination: 14%. Infection with multidrug resistant M. tuberculosis (TB-MR):
      20%. M. tuberculosis was isolated from other clinical samples in 79%. Fifteen
      patients received treatment for tuberculosis; in 30% of cases, it was not
      appropriate due to the susceptibility of the isolated strain. Overall mortality
      was 66.4%. CONCLUSION: high mortality was observed, which may be attributable to
      the high frequency of TB-MR, the level of immunosuppression and the prevalence of
      cirrhosis secondary to enolism and/or HCV coinfection.

PMID- 21186671
TI  - [Otomyiasis by Cochliomyia hominivorax in two children from the outskirts of
      Buenos Aires, Argentina].
AB  - Cochliomyia hominivorax causes 80% of human myiasis in Argentina. Nowadays, its
      geographic distribution covers tropical South America and an important region of
      Argentina. In the present report, two clinical cases of otomyiasis by C.
      hominivorax in pediatric patients assisted at the Hospital de Clinicas of Buenos
      Aires, Argentina are described. The relevance of the taxonomic identification
      lies in the fact that this species produces severe symptoms owing to the capacity
      of its larvae to drill the bones and cause the host's death.

PMID- 21186672
TI  - [Evaluation of the immune response after vaccination against distemper at a mink
      (Mustela vison) farm in Argentina].
AB  - Distemper virus causes a disease affecting minks with respiratory,
      gastrointestinal, neurological and skin symptoms and showing high morbidity and
      mortality, mainly among puppies. It is controlled through immunization, using
      vaccines that are supplied for mink use. The aim of this work was to determine
      the seroneutralization titer against the distemper virus at a mink farm in
      Argentina. The antibody kinetics obtained after vaccination in 27 adult animals,
      as well as the duration of colostrum-transferred antibodies in 10 puppies were
      determined. All vaccinated adult minks showed protective titers up to at least 3
      months after vaccination, and 37.5% significantly reduced their antibody levels,
      12 months after vaccination. Only 20% of the puppies showed protective levels of
      colostrum-transferred antibodies at the age of 7 weeks, while non-detectable
      levels of antibodies were found when puppies reached 11 weeks old. Vaccination
      performed in these puppies at the age of 13 weeks, elicited protective
      seroneutralization titers. These results show that vaccination induces a
      satisfactory humoral immune response in our environment, and support the
      convenience of vaccinating dams annually before the beginning of the breeding
      season. The vaccination plan in puppies is also discussed.

PMID- 21186673
TI  - [In vitro activity of doripenem and other carbapenems against Pseudomonas
      aeruginosa].
AB  - Doripenem, a new carbapenem, has shown to be more active against Pseudomonas
      aeruginosa than other carbapenems. The activity of doripenem, imipenem and
      meropenem was evaluated against 93 P. aeruginosa isolates, by agar dilution and
      disk diffusion methods. MIC50 and MIC90, were as follows (microg/ml): doripenem,
      2 and 4; meropenem, 2 and 8; and imipenem, 4 and 8, respectively. Doripenem MICs
      were 1 to 3 dilutions lower (i.e. more active) than those for imipenem in 82% of
      the isolates. In comparison with meropenem, doripenem was 1 to 3 dilutions more
      active in 50% of the isolates. Forty-nine percent of isolates showed the same MIC
      for both antibiotics. Resistance percentages for both methods were
      (dilution/diffusion): imipenem = 7.5%/49.5% and meropenem = 3.2%/9.7%. As the
      CLSI has not established cut off values for doripenem yet, resistance rates for
      this antibiotic were estimated by considering (a) the same cut off values for
      imipenem/meropenem set up by the CLSI, and (b) those suggested by Brown et al. In
      case (a), resistance rates would be 1.1%/2.2% whereas in case (b) 1.1%/17.2% for
      agar dilution and disk diffusion, respectively. In scenarios where resistance to
      carbapenem is based on mechanisms other than carbapenemases, doripenem has a
      promising future for treating P. aeruginosa infections.

PMID- 21186674
TI  - [Staphylococcus aureus: new and old antimicrobial agents].
AB  - The objective of the study was to evaluate the susceptibility to old and new
      antimicrobial agents against hospital-acquired oxacillin-resistant Staphylococcus
      aureus (HA-ORSA), community-acquired oxacillin-resistant S. aureus (CA-ORSA), and
      oxacillin-susceptible S. aureus(OSSA). The minimum inhibitory concentration of
      different antimicrobial agents against 118 S. aureus consecutive and prospective
      isolates was studied by the CLSI agar dilution method. In ORSA isolates without
      accompanying resistance, the mecA gene, the Panton-Valentine leukocidin gene
      (PVL), and the gamma-hemolysin gene were determined by PCR, and the SCC cassette
      mec gene by multiplex PCR. Out of the 118 isolates, 44 were HA-ORSA, 16 were CA
      ORSA, and 58 corresponded to OSSA. The HA-ORSA isolates presented simultaneous
      resistance to erythromycin, clindamycin, gentamicin, ciprofloxacin, levofloxacin,
      and moxifloxacin whereas all of them were susceptible to tigecycline (TIG),
      vancomycin, teicoplanin and linezolid (LZD). The CA-ORSA isolates were only
      resistant to OXA and presented susceptibility to all the antimicrobial agents
      assayed. In all of them, the mec-A gene, the PVL gene, the gamma-hemolysin gene
      and the SCC cassette mec type IV gene were detected. With the OSSA and CA-ORSA
      isolates, all the non-beta-lactam antimicrobial agents assayed exhibited
      excellent in vitro activity. However, in the HA-ORSA isolates, only the old
      antimicrobial agents such as glycopeptides, doxyciclin, rifampin, and
      trimethoprim-sulfamethoxazole and the new antimicrobial agents LZD and TIG,
      presented good in vitro activity. The ORSA phenotype without accompanying
      resistance was highly predictive of CA-ORSA as confirmed by a positive SCC
      cassette mec type IV.

PMID- 21186675
TI  - [Multiplex PCR for the detection of sea, seb, sec, sed and see genes of
      Staphylococcus aureus. Characterization of isolates from food].
AB  - Multiplex PCR for the detection of sea, seb, sec, sed and see genes of
      Staphylococcus aureus. Characterization of isolates from food. The presence of
      Staphylococcus aureus in food represents a potential risk to public health, being
      its enterotoxins the major virulence factor. Enterotoxin detection can be
      determined by ELISA, but only for the pool of enterotoxins SEA, SEB, SEC, SED and
      SEE. The main aims of this study were to optimize two PCR techniques for
      detection of S. aureus sea, seb, sec, sed and see, and to characterize
      Staphylococcus spp. isolates associated with food intoxication. Two PCR
      techniques were optimized and 115 Staphylococcus spp. isolates from Ciudad
      Aut6noma de Buenos Aires, and Buenos Aires, Cordoba, and Neuquen provinces were
      characterized. The characterization was performed by biochemical tests, ELISA and
      PCR. Sixty-eight isolates (59.1%) were positive by ELISA, while 61 (53%) were
      positive by PCR. Out of the positive PCR isolates, 34 (55.7%) carried the sea
      gene, 9 (14.8%) the seb gene, 5 (8.1%) the see gene, 4 (6.5%) the sec gene, 6
      (9.9%) were positive for sea and seb genes, 2 (3.3%) for sea and sec genes, and 1
      (1.7%) for sea and sedgenes. This is the first study of genotypic
      characterization of S. aureus isolates associated with food intoxication from
      different provinces of Argentina.

PMID- 21186676
TI  - [Secondary syphilis: different genital lesions in an heterosexual couple].

PMID- 21186677
TI  - [Immunodetection of Mycobacterium avium paratuberculosis p34 in infected bovine
      macrophage].

PMID- 21186678
TI  - [Does the combination syndrome exist? A case report].
AB  - This case report documents the prosthetic rehabilitation of a patient showing the
      typical features of combination syndrome. This case documentation gives a general
      overview of the suspected development and the prevalence of this "syndrome". A
      treatment option should be shown by the example of a patient from the starting
      situation until the prosthetic therapy by means of a complete maxillary denture
      and an implant-supported mandibular overdenture rigidly retained with a milled
      bar.

PMID- 21186679
TI  - Health, leisure and sociability at the turn of the nineteenth century: Jewish
      women in German spas.

PMID- 21186680
TI  - "Schutzjuden" and opportunistic criminality in the early modern period: the
      Lemmel family from Neustadt-Eberswalde .

PMID- 21186681
TI  - Diaspora, faith, and science: building a Mouride hospital in Senegal.
AB  - This article examines a development initiative spearheaded by the members of a
      transnational diaspora - the creation of a medical hospital in the holy city of
      Touba in central Senegal. Although the construction of the hospital is decidedly
      a philanthropic project, Hopital Matlaboul Fawzaini is better understood as part
      of the larger place-making project of the Muridiyya and the pursuit of symbolic
      capital by a particular Mouride "dahira". The "dahira's" project illuminates
      important processes of forging global connections and transnational localities,
      and underscores the importance of understanding the complex motivations behind
      diaspora development. The hospital's history reveals the delicate negotiations
      between state actors and diaspora organizations, and the complexities of public
      private partnerships for development. In a reversal of state withdrawal in the
      neo-liberal era, a diaspora association was able to wrest new financial
      commitments from the state by completing a large infrastructure project. Despite
      this success, we argue that these kinds of projects, which are by nature uneven
      and sporadic, reflect particular historical conjunctures and do not offer a
      panacea for the failure of state-led development.

PMID- 21186682
TI  - Wieland's nude bathers: visual pleasure and the female gaze.
AB  - In her essays on Wieland, written around 1980, Elizabeth Boa went against
      contemporary fashion both by praising a neglected writer and by vindicating the
      role of pleasure in the reception of literature. She noted how Wieland varies a
      literary topos - a man watching a woman bathing naked - by letting women watch
      men bathing naked. This topos most often occurs in the pastoral, a popular
      eighteenth-century genre. Various examples are examined to show that they suggest
      equality rather than male dominance in relations between the sexes: men watching
      women bathing in James Thomson and Gottfried Keller; an example involving cross
      dressing in Kleist; and finally women watching men bathing naked in Swift,
      Voltaire and Wieland's Idris und Zenide.

PMID- 21186683
TI  - The Faustian "Gretchen": overlooked aspects of a famous male fantasy.
AB  - This essay takes issue, on the one hand, with the traditional interpretation of
      Goethe's Margarete as representing the Natural, the Naive, and the selflessly
      loving feminine as well as, on the other hand, the feminist interpretation of
      Margarete as a male fantasy figure who props up the masculine self-perception of
      the male as a dominant and titanic "striver." Both interpretative tendencies
      overlook the close analogy with which Margarete's aspirations and behaviour
      mirror Faust's own regarding a shared readiness to rebel, break all the rules,
      and dare the ultimate, which gives Margarete her own independent agenda, makes
      her an individual in her own right. In this light the three key paradigms of
      femininity - Madonna, whore/witch, and nature - which shape the presentation of
      this character are investigated, as well as the relation of the
      "Gretchentragodie" to notions of the classical, the role of sexual fulfilment in
      Margarete's decision-making, and the significance of this character's two names.
      The essay concludes that, excepting the area of intellectualised self
      consciousness, Margarete must be regarded as a striving individual who engages in
      autonomous activity, which much previous criticism has made the domain of the
      self-determined modern male subject.

PMID- 21186684
TI  - Sexing Berlin?
AB  - Berlin has always been a literary space of extremely diverse political and
      cultural projections. This essay investigates why after the unification of East
      and West Berlin the city has been imagined as a play zone of sexual self
      fulfilment by authors such as Inka Parei, Tanja Duckers, Kathrin Roggla, Judith
      Hermann and Julia Franck. Have such erotic adventures replaced political vision
      in our post-utopian decade? What is the purpose of the laboured allegorisation of
      the fall of the wall in Durs Grunbein's essays or in the novels of Katja Lange
      Muller and Thomas Hettche? The sexification of historical and political processes
      recalls similar stereotypes in the East German literature of the 1980s: the
      metropolis as a whore in works by Heiner Muller or Wolf Biermann, but also by
      younger authors of the independent literary scene in Berlin like Uwe Kolbe or
      Frank-Wolf Matthies.

PMID- 21186685
TI  - The floods of 589 and climate change at the beginning of the Middle Ages: an
      Italian microhistory.

PMID- 21186686
TI  - The Rockefeller Foundation and the post-WW2 transnational ecology of science
      policy: from solitary splendor in the inter-war era to a "me too" agenda in the
      1950s.

PMID- 21186687
TI  - Uranium in glass.

PMID- 21186688
TI  - Meeting reports. SRP One-Day Conference--Practical Design of Radioactive
      Facilities. Birmingham & Midlands Institute, Birmingham, UK, 9 November 2010.

PMID- 21186689
TI  - [Preventive detention and adolescents - an objection!].

PMID- 21186690
TI  - Risk charts--very popular but useless?

PMID- 21186691
TI  - Varicose veins: hemodynamic phenomenon or primary wall defect? Which is the egg
      and which is the hen?

PMID- 21186692
TI  - [International child and adolescent psychiatric research in Gottingen - for
      Aribert Rothenberger on his 65th birthday].

PMID- 21186693
TI  - Glucocorticoid-induced  osteoporosis.

PMID- 21186694
TI  - Bariatric surgery, vitamin  C, and kidney stones.

PMID- 21186695
TI  - Sexual dimorphism in intra- and interspecific competitive ability of the
      dioecious herb Mercurialis annua.
AB  - Males and females of dioecious plant species often show different responses to
      competition with individuals of the same or opposite gender, but almost no data
      are available on the outcome of competition with members of other species. Here,
      we show that male and female individuals of the wind-pollinated herb Mercurialis
      annua are sexually dimorphic in both their intraspecific and interspecific
      competitive abilities. In a controlled experiment, we found that both sexes of M.
      annua were negatively affected by interspecific competition, but the sensitivity
      of males and females depended on the identity of their competitor species, with
      females tending to suppress the aboveground growth of competitor species more
      than males. Further, we found that intrasexual and intersexual competition
      affected the aboveground growth of males but not that of females: only males
      showed a significant reduction in growth when growing with conspecific
      competitors (male or female). We discuss our results with reference to related
      studies that suggest that males and females of M. annua have different resource
      requirements for reproduction, which in turn affect their competitive abilities.

PMID- 21186696
TI  - Retraction. Growth, ion homeostasis, photosynthesis and photosystem II efficiency
      of an obligate halophyte, Salicornia brachiata, under increasing salinity.

PMID- 21186697
TI  - [Dissemination of German medicine in Spain and Latin America: the "Revista Medica
      de Hamburgo" and the "Revista Medica Germano-Ibero-Americana" (1920-1933)].
AB  - This article presents the development of the journals "Revista Medica de
      Hamburgo" and "Revista Medica Germano-Ibero-Americana," which were created to
      promote and disseminate the German science among the medical community in Latin
      America and Spain between the two World Wars. Shaken by the loss of Germany's
      colonies in Africa, the difficulties faced due to post-war economy, and the
      restrictions imposed by the armistice, the Germans sought to restore their
      cultural and scientific prestige through such initiative.

PMID- 21186698
TI  - [The foundational myth of Argentinian homeopathy. The journal "Homeopatia,"
      Buenos Aires (1933-1940)].
AB  - The present article analyzes the historical-identitary construction in the older
      and most important institution of Homeopathy in Argentina. Two analytical axes
      are constructed: on the one hand, the construction of a foundational myth that
      outlines a genealogical thread between the "divinities" of the medicine, and on
      the other hand, the mitification of Hahnemann, founding father of the discipline.
      Using both axes we explain how the discourses of the journal were creating a
      symbolic support for the weak conjuncture in which they tried to be consolidated
      legally as an institution.

PMID- 21186699
TI  - [The journal "Broteria," Jesuit botanists and Goncalo Sampaio. Exchange of plants
      and ideas, and the development of botany in Portugal].
AB  - The journal Broteria has covered a long path, since its foundation in 1902 until
      the mid 20's, when it stands as one of the best journals of natural history and a
      voice of the renewal of the natural sciences in Portugal. Broteria's success was
      due, mainly, to the remarkable qualities of its founders and main editors: their
      working capacity, intellectual standards and perseverance as well as the ability
      to establish a network of naturalists who sent them biological collections from
      remote regions and the ability to adapt to exile, while continuing to work and
      focusing their studies on the natural history of the exile country. The
      maintenance, in regular functioning, of their schools, and the opening to the
      collaboration of non Jesuit naturalists, such as the botanists from Oporto, also
      contributed to the success of Broteria.

PMID- 21186700
TI  - Accountable care organizations: an opportunity for physicians.

PMID- 21186701
TI  - Clarifying the deadline for meaningful use of EHR systems.

PMID- 21186702
TI  - Doing more with less: practices tackle today's healthcare challenges.

PMID- 21186704
TI  - Final EHR rules make compliance easier but relief is temporary.
AB  - The final federal rules make it easier to meet Stage 1 requirements, but are not
      expected to significantly change the outcomes expected by the conclusion of Stage
      3 in 2015. Practices that have not already done so should begin a detailed
      planning process, as outlined above, so they can meet Stage 1 requirements by the
      deadline at the end of 2012.

PMID- 21186703
TI  - What would have made a difference?

PMID- 21186705
TI  - Coding from the trenches.

PMID- 21186706
TI  - Catastrophic antiphospholipid antibody syndrome in a young woman in the
      postpartum period.
AB  - A 27-year-old Hispanic female was admitted to hospital with fever, a sudden
      marked decrease in vision, and multi-organ failure shortly after preterm delivery
      by cesarean section for eclampsia. Her past history was significant for a
      spontaneous first trimester abortion and one live birth complicated by
      intrauterine growth retardation. She was found to have several focal brain
      infarcts, exudative retinal detachment, bilateral adrenal hemorrhage, renal
      insufficiency, hypertension and subsequently hypotension. Positive
      anticardiolipin antibodies, lupus anticoagulant, and anti-B2 glycoprotein-I, as
      well as deranged coagulation profile and PTT mixing studies aided in the
      diagnosis of catastrophic antiphospholipid antibody syndrome. Anticoagulation and
      high-dose intravenous steroids led to significant improvement in the patient's
      condition, including her vision.

PMID- 21186707
TI  - Lactic acidosis in restrained cocaine intoxicated patients.
AB  - Severe lactic acidosis has been reported in patients struggling against
      restraints, especially in association with the use of stimulant drugs, such as
      cocaine. Profound acidosis occurring under these conditions can lead to cardiac
      arrhythmias, autonomic instability and cardiac arrest, a syndrome known as
      restraint associated asphyxia. Early recognition of this condition and removing
      the stimulus for lactic acid production (excessive muscle activity) by aggressive
      sedation and ventilatory assistance, coupled with fluid administration to improve
      tissue perfusion and lactate metabolism, can be life-saving. The current report
      describes a case of restraint associated severe lactic acidosis in a cocaine
      intoxicated patient that was successfully treated by sedation, muscular paralysis
      and mechanical ventilation. Public safety personnel must be aware of this
      potentially life threatening complication. Avoiding hobble and prone restraint
      positions may eliminate some of the problems that contribute to the
      pathophysiology of this condition.

PMID- 21186708
TI  - Effect of surfactants on phosphatase level of fresh water fish Labeo rohita.
AB  - Alterations in the activity of enzymes Acid phosphatase (E.C.3.1.3.2) and
      Alkaline phosphatase (EC 3.1.3.1) in organs such as liver, gills and muscle of
      rohu following its exposure to surfactants viz. CTAB, SDS and Triton X-100 were
      analyzed. Different levels of exposure were given depending on the LC50 value of
      the surfactant used. Also, the influence of age and weight of the organisms was
      tested simultaneously. The activity of ACP in the tissues of fish exposed to all
      the three surfactants showed marked enhancement after exposure; the effect being
      highest in the liver followed by gill and muscle. Activity levels of ALP in
      different tissues of the fish exposed to the surfactants also showed an increase.
      Maximum increase was found in the liver followed by muscle, and gill. The
      increase in the levels of these enzymes indicates a stressful condition of the
      fish.

PMID- 21186709
TI  - Bioefficacy of insecticides against Leucinodes orbonalis on brinjal.
AB  - Studies on bioefficacy of insecticides against brinjal shoot and fruit borer,
      Leucinodes orbonalis Guenee on brinjal were carried out during 2007 and 2008. The
      results on bioefficacy of insecticides showed that in terms of shoot infestation,
      emamectin benzoate (0.002%), endosulfan (0.05%), novaluron (0.01%) and lambda
      cyhalothrin (0.004%) were found superior. The total number of drooping shoots was
      minimum (4.17) in emamectin benzoate followed by endosulfan (6.83) and novaluron
      (7.00), as compared to spinosad (9.17), deltamethrin (11.67) and Bacillus
      thuringiensis (13.17). In terms of reduction in fruit infestation, emamectin
      benzoate (0.002%) was highly effective followed by endosulfan (0.05%), agrospray
      oil T (0.2%) and spinosad (0.0024%). However, cost benefit ratio was highest in
      agrospray oil T (0.2%) followed by lambda-cyhalothrin (0.004%), endosulfan
      (0.05%) and deltamethrin (0.0028%).

PMID- 21186710
TI  - Identification of species-specific RAPD markers in genus Cenchrus.
AB  - Cenchrus is an important component of major grass cover of world. Similar to the
      other major tropical grasses most of the species in genus Cenchrus are also
      apomictic in nature hence correct and precise identification of accessions and
      species are problematic and dubious. In the present study 187 decamer
      oligonucleotide primers were tested for PCR-based DNA amplification of six
      prominent species of genus Cenchrus. Of these, 32 potential repetitive and
      polymorphic primers were tested for identification of species-specific markers
      for C. ciliaris, C. setigerus, C. pennisetiformis, C. prieurri, C. biflorus and
      C. myosuroides. These primers yielded 51 unique RAPD markers either specific to a
      species (37) or shared by two or more species (14). Maximum markers were shared
      between C. ciliaris and C. setigerus confirming theirmore closeness to each other
      Primers like OPF09, OPF11, OPR15, OPAJ11, OPQ10 and OPAK20 generated strong
      intense bands can be used on priority in identifying the species from their
      natural habitat for the development of species-specific core germplasm. Due to
      apomictic nature this is the prime method of developing cultivars, as
      morphological characters are largely unable to distinguish them. The level of
      variation observed clearly suggest RAPD as an appropriate marker for genetic
      studies and in identifying the lines with species-specific markers for Cenchrus
      germplasm management activity and also maintaining identity and purity for
      proprietary reasons.

PMID- 21186711
TI  - Effect of neem extract against the bacteria isolated from marine fish.
AB  - Marine ornamental fishes are exceedingly valuable due to their high demand in
      domestic and international markets. There is a growing global interest to rear
      the fishes in captivity. But problem due to bacteria and fungi are the major
      hitch in captive condition. Since, the use of antibiotics is banned, an attempt
      was made to ascertain in vitro assay of the neem leaves extract against the
      bacterial pathogens isolated from infected fishes. Bacterial strains isolated
      from infected regions of the clown fishes Amphiprion sebae and A. ocellaris were
      identified as Aeromonas hydrophila, Enterobacter sp., E. coli, Pseudomonas
      aeruginosa, Proteus sp., Streptococcus sp., Vibrio cholerae, V. alginolyticus, V.
      parahaemolyticus and Yersinia enterocolitica. Ethanol and methanol extracts were
      highly inhibitory to the bacterial isolates when compared to other solvents.
      Ethanol extracts exhibited low minimum inhibitory concentration (75-250 microg
      ml(-1)) as compared to other extracts. The present finding revealed that the neem
      leaf extract significantly reduces the bacterial pathogens and their infection in
      marine ornamental fishes.

PMID- 21186712
TI  - Induction of oxidative stress by non-lethal dose of mercury in rat liver:
      possible relationships between apoptosis and necrosis.
AB  - Sprague Dawley strain of male rats weighing 200 +/- 10.0 g, were exposed
      intramuscularly to non-lethal dose of mercury for short acute duration of 24 and
      48 hr. Mercury treatment increased thio-barbituric acid reactive substance
      (TBARS) and conjugated diene (CD) content with increase in duration when compared
      with control. This reflects possible increase in lipid peroxidation, revealing
      that sufficient intoxication was generated by non-lethal dose of mercury.
      Furthermore, mercury treatment decreased tissue glutathione (GSH) content to 2.07
      and 1.49 microg GSH mg protein(-1) with concomitant decrease in glutathione-S
      transferase (GST) activity by 26.06 and 36.40% after 24 and 48 hr of exposure
      respectively. The elevations of aspartate transaminase (AST) and alanine
      transaminase (ALT) levels measured exhibited increase of 287.5 and 214.5% after
      48 hr of exposure respectively which were found to be highly significant compared
      with control. Western blot analysis indicated upregulation of caspase-9 and
      upsurge in effect or caspase-3 activity leading to apoptosis. The concluded
      findings of the present investigation suggests possible role of early mercury
      exposure in inducing oxidative stress mediated apoptosis in mammalian model
      systems as an indicator component of environmental toxicology.

PMID- 21186713
TI  - Analysis of AchE and LDH in mollusc, Lamellidens marginalis after exposure to
      chlorpyrifos.
AB  - The enzymes Acetylcholinesterase (AchE) and Lactatedehydrogenase (LDH) are used
      as biological markers in the present study. Enzymes are highly sensitive and used
      to evaluate the biological effects of organophosphate pesticide chlorpyrifos in
      freshwater mussel Lamellidens marginalis. The test organisms were exposed to sub
      lethal concentration (5 ppm) of chlorpyrifos for 30 days and allowed to recover
      for seven days. A distinct reduction of the enzyme AchE (34 +/- 3.3 U l(-1)) was
      found in the treated hepatopancreas. A significant increase in LDH activity in
      gill, hepatopancreas and muscle was observed. There was a significant recovery in
      AchE and LDH in the different tissues, after seven days recovery period.. Hence,
      the changes in the enzymes are found as the best biomarkering tool to evaluate
      the effect of organophosphate pesticide chlorpyrifos on the aquatic biota.

PMID- 21186714
TI  - Accumulation and translocation of heavy metals in soil and plants from fly ash
      contaminated area.
AB  - The present investigation deals with the accumulation of heavy metals in fields
      contaminated with fly ash from a thermal power plant and subsequent uptake in
      different parts of naturally grown plants. Results revealed that in the
      contaminated site, the mean level of all the metals (Cd, Zn, Cr, Pb, Cu, Ni, Mn
      and Fe) in soil and different parts (root and shoots) of plant species were found
      to be significantly (p<0.01) higher than the uncontaminated site. The enrichment
      factor (EF) of these metals in contaminated soil was found to be in the sequence
      of Cd (2.33) > Fe (1.88) > Ni (1.58) > Pb (1.42) > Zn (1.31) > Mn (1.27) > Cr
      (1.11) > Cu (1.10). Whereas, enrichment factor of metals in root and shoot parts,
      were found to be in the order of Cd (7.56) > Fe (4.75) > Zn (2.79) > Ni (2.22) >
      Cu (1.69) > Mn (1.53) > Pb (1.31) > Cr (1.02) and Cd (6.06) approximately equal
      Fe (6.06) > Zn (2.65) > Ni (2.57) > Mn (2.19) > Cu (1.58) > Pb (1.37) > Cr (1.01)
      respectively. In contaminated site, translocation factor (TF) of metals from root
      to shoot was found to be in the order of Mn (1.38) > Fe (1.27) > Pb (1.03) > Ni
      (0.94) > Zn (0.85) > Cd (0.82) > Cr (0.73) and that of the metals Cd with Cr, Cu,
      Mn, Fe; Cr with Pb, Mn, Fe and Pb with Fe were found to be significantly
      correlated. The present findings provide us a clue for the selection of plant
      species, which show natural resistance against toxic metals and are efficient
      metal accumulators.

PMID- 21186715
TI  - Impact of fishing methods on conservation of ichthyofauna of river Relli in
      Darjeeling Himalaya of West Bengal.
AB  - Impact of fishing methods and gears used on fish faunal diversity in spring-fed
      torrential river Relli in Darjeeling hill area of West Bengal was investigated in
      the present study. The fish species available in the river provide nutrition and
      recreation (rarely income generating) fora large number of people residing along
      the river bank and nearby villages and towns. The fishing methods observed
      therein have been categorized as, i) Scientific fishing methods, that is,
      collection of required number and size of fish so that sufficient population of
      fish remains balanced in the nature. ii) Unscientific fishing methods, that is,
      indiscriminate killing of large number of fish which adversely affect the water
      quality of rivers. Ten types of fishing methods are practiced in this area, for
      example, diversion of river channel, cast netting, scoop netting, angling, fish
      spearing, rock striking or hammering, dynamiting, electric fishing, river
      poisoning and traps utilized. Over the years uncontrolled and often
      indiscriminate fishing in the unmanaged hill-stream has resulted in a sharp
      decline in fish resources. The study gives a clear picture on the anthropogenic
      pressure on the river Relli and provides baseline data which may be helpful for
      conservation and management of the fish species and also formulating new fishery
      policy.

PMID- 21186716
TI  - Drought stress induced changes in lipid peroxidation and antioxidant system in
      genus Avena.
AB  - Seven species of genus Avena viz., Avena sativa, Avena strigosa, Avena brevis,
      Avena vaviloviana, Avena abyssinica, Avena marocana and Avena sterilis were used
      to study the impact of drought stress on lipid peroxidation and other antioxidant
      enzymes. Maximum increase in the catalase activity was recorded in A. vaviloviana
      (129.97%) followed by A. sativa (122.82%) and A. brevis (83.38%) at vegetative
      stage; however at flowering stage the maximum increase was reported in A. sativa
      (25.62%) followed by A. sterilis (20.46%) and A. brevis (18.53%). At vegetative
      stage drought, maximum increase in peroxidase activity was recorded in A. sativa
      (122.82%) followed by A. brevis (83.38%) and A. sterilis (49.78%). Flowering
      stage drought, showed maximum increase in A. Sativa (27.09%) followed by A.
      marocana (23.50%) and A. sterilis (20.46%). A. sativa and A. sterilis showed
      stress tolerance at both the stages by accumulating higher percentage of
      peroxidase followed by A. brevis at vegetative and A. marocana at flowering
      stage. Level of lipid peroxidation in terms of Malondialdehyde (MDA) content was
      increased in the leaves when plants were subjected to moisture stress. The rate
      of increase in lipid peroxidation occurs irrespective of stage however; maximum
      increase was recorded in A. strigosa at both the stages. Avena species which
      showed high level of MDA content, indicates more lipid peroxidation and more
      membrane permeability and are comparatively more susceptible for water stress
      than those which produce less Malondialdehyde (MDA) content at higher magnitude
      of water stress such species have better capability for moisture stress
      tolerance.

PMID- 21186717
TI  - Bioremediation of industrial waste through mushroom cultivation.
AB  - Handmade paper and cardboard industries are involved in processing of cellulosic
      and ligno-cellulosic substances for making paper by hand or simple machinery. In
      the present study solid sludge and effluent of both cardboard and handmade paper
      industries was collected for developing a mushroom cultivation technique to
      achieve zero waste discharges. Findings of present research work reveals that
      when 50% paper industries waste is used by mixing with 50% (w/w) wheat straw,
      significant increase (96.38%) in biological efficiency over control of wheat
      straw was observed. Further, cultivated basidiocarps showed normal morphology of
      stipe and pileus. Cross section of lamellae did not show any abnormality in the
      attachment of basidiospores, hymenal trama and basidium. No toxicity was found
      when fruiting bodies were tested chemically.

PMID- 21186718
TI  - Biodegradation of mono-chlorobenzene by using a trickle bed air biofilter (TBAB).
AB  - In the present study, performance of the trickle bed airbiofilter (TBAB) for
      treating mono-chlorobenzene (MCB) was evaluated for various influent volatile
      organic compound (VOC) loadings using coal and mixed consortium of activated
      sludge as the packing material. Microbial acclimation to MCB was achieved by
      exposing the system continuously for 31 d to an average inlet MCB concentration
      of 0.688 g m(-3) at an empty bed residence time (EBRT) of 188 s. The TBAB
      achieved maximum removal efficiency of 87% at an EBRT of 188 s for an inlet
      concentration of 0.681 g m(-3), which is quite significance than the values
      reported in the literature. Elimination capacities of MCB increased with an
      increase of the influent VOC loading, but an opposite trend was observed for the
      removal efficiency The maximum elimination capacity of the biofilter was 110.75 g
      m(-3) hr(-1) at an inlet MCB concentration of 1.47 g m(-3). The effect of
      starvation on the TBAB was also studied. After starvation, the TBAB lost its
      ability to degrade MCB initially However the biofilter recovered very quickly
      Evaluation of the concentration profile along the bed height indicated that the
      bottom section of TBAB has the best performance for all concentrations. By using
      Wani's method of macrokinetic determination based on simple Monod kinetics, the
      maximum removal rate of MCB, r(max) and saturation constant K(m) was to be found
      as 1.304 g m(-3)s(-1) and 113.446 g m(-3), respectively.

PMID- 21186720
TI  - Effect of salinity on survival and growth of blue crab, Callinectes amnicola from
      Lagos Lagoon, Nigeria.
AB  - The effect of salinity on the survival and growth of Callinectes amnicola (De
      Rocheburne) from the Lagos Lagoon, Nigeria was monitored in the laboratory for 22
      weeks. The crabs were euryhaline and tolerated a salinity range of 5 to 25 per
      thousand and had 90% survival at 15 and 20 per thousand. The highest gain in
      weight (173.0%) and carapace width (56.1%) was obtained at salinity of 15 per
      thousand. The highest specific growth rate (1.98) was obtained at 15 per
      thousand, while the lowest specific growth rate (-0.28) was recorded at 35 per
      thousand. The condition factor of the crabs showed a fairly consistent pattern at
      the different salinity levels with values ranging from 5.7 to 7.3. Complete
      moulting was obtained at salinity of 15 per thousand in the 12th week of the
      experiment. The crab with carapace width of 6.8 cm increased to 8.1 cm (19.1%)
      after moulting.

PMID- 21186719
TI  - Effect of defoliation by the pine processionary moth (PPM) on radial, height and
      volume growth of Crimean pine (Pinus nigra) trees in Turkey.
AB  - In this study, we assessed the effects of chronic defoliation on radial, height
      and volume growth of Crimean pine (Pinus nigra Arnold) trees of the pine
      processionary moth [Thaumetopoea wilkinsoni Tams (Lepidoptera:Thaumetopoeidae)]
      in western Turkey Crimean pine tree ring chronologies were analyzed for evidence
      of the pine processionary moth (PPM). Tree ring widths from non-defoliated
      Crimean pine sample trees, which were not defoliated by PPM from 1998 to 2004,
      were used to estimate potential growth in the defoliated Crimean pine sample
      trees during the same time interval. In 2004, increment cores collected from 50
      defoliated sample trees and 25 non-defoliated sample trees dominant or co
      dominant trees. Annual radial growth indices from 1985-2004 calculated for each
      defoliated Crimean pine and non-defoliated Crimean pine group. We identified
      regional outbreaks of PPM by synchronous and sustained growth periods of Crimean
      pine trees. Growth functions of defoliated Crimean pine trees (3) and non
      defoliated Crimean pine trees (2) were graphically compared as the cumulative sum
      of radial, height and volume increment. Two outbreak were identified in 1992
      (1992 and 1993) and 1998 (1998-2004) in the study area. PPM caused a significance
      decrease (average 33%, p<0.05) in the annual radial increment in 1998-2004.

PMID- 21186721
TI  - The investigation of cytotoxic effects of refinery wastewater on root tip cells
      of Vicia faba L.
AB  - The present study was carried out to evaluate the cytotoxic effects of refinery
      wastewater collected from different stations of the Kizilirmak river on Vicia
      faba L. root tip cells. For this aim, we used the germination percentage, root
      length, weight gain and micronucleus (MN) frequency as indicators of
      cytotoxicity. Additionally to the cytological analysis, DNA analyses were
      performed in root tips meristems of Vicia faba seeds treated with refinery
      wastewater. Heavy metal concentrations in the water samples were determined using
      atomic absorption spectrophotometer (AAS). The concentrations of heavy metals in
      the water were in the order of Pb>Zn>Fe>Cu>Ni>Cd>Hg. The highest germination
      percantage was observed in the control group (in proportion as 96%). Heavy metals
      in the water samples collected from Station I, II and III caused a decrease in
      the germination percentage as 48, 18 and 30%, respectively. The highest root
      length and weight gain was observed in the control group at the end of the
      experimental period. The least root length and weight gain was observed in seeds
      treated with wastewater collected from Station I. In the control group, the
      weights of all the seeds increased about 4.08 g when compared with initial
      weight. The root lengths of the control seeds were determined as 6.38 cm at the
      end of the experimental period. The weights of the seeds exposed to wastewaters
      obtained from Station I, II and III increased about 1.08, 3.03 and 2.01 g
      according to initial weight, respectively. Microscopic examination of V. faba
      root tip meristem cells showed that any example of the MN formation was not seen
      in the control group. The highest frequency of MN was observed in group treated
      with wastewater collected from Station I and least frequency of MN was observed
      in group treated with wastewater collected from Station II. It was also observed
      that the yields of DNA in the seeds exposed to wastewater were lower than
      recorded in the controls. Hence, DNA yields exposed to wastewater were run ahead
      on agarose gel according to the control group. The results clearly indicate that
      refinery wastewater had important cytotoxic effects on V. faba root tip cells. It
      was also observed that V. faba seeds are very sensitive and useful biomarkers for
      monitoring these effects in waters contaminated with heavy metals.

PMID- 21186722
TI  - Ecotoxicological characterization of tannery wastewater in Dhaka, Bangladesh.
AB  - Tanning industries are one of the main economic activities in Bangladesh. It has
      been well documented that wastewater discharged from tanneries without
      appropriate treatment results in detrimental effects on the ecosystem. No
      ecotoxicity evaluation of any aquatic environment in Bangladesh has been
      conducted so far. In this study a battery of toxicity bioassays and chemical
      analysis were carried out from water samples obtained from three sampling points:
      upstream from discharging site on River Buriganga (S1), raw wastewater effluent
      (S2), and downstream the discharging sluice gate (S3), in the Hazaribagh tannery
      area of Dhaka City, Bangladesh. While S1 and S3 water samples did not show
      significant toxicity in the bioassays tested, S2 exhibited high acute toxicity to
      the bacterium Vibrio fischeri (15-min Microtox test, EC50 = 9.8%), the higher
      plant Lactuca sativa (5-day root elongation inhibition test, EC50 = 14.2%), and
      the microcrustacean Daphnia magna (24-hour mobility test, EC50 = 31.5%). The
      results suggested that the raw wastewater effluent had detrimental effects on
      broad spectrum of organisms in the aquatic ecosystem and bacterium was the most
      sensitive. The chemical analysis revealed that sample S2 contained an extremely
      high concentration of chromium (47 g l(-1)). Additionally microbiological
      analysis indicated that the sampling area is impacted by fecal pollution,
      increasing the environmental health risk for its inhabitants.

PMID- 21186723
TI  - Impacts of repeated timber skidding on the chemical properties of topsoil,
      herbaceous cover and forest floor in an eastern beech (Fagus orientalis Lipsky)
      stand.
AB  - In this study, long-term timber skidding effects on herbaceous understory forest
      floor and soil were investigated on a skid road in a stand of the eastern beech
      (Fagus orientalis Lipsky). For this purpose, herbaceous understory forest floor
      and soil samples were collected from the skid road and from an undisturbed area
      used as a control plot. The mass (kg ha(-1)) of herbaceous and forest floor
      samples was determined, and soil characteristics were examined at two depths (0-5
      cm and 5-10 cm). We quantified sand, silt and clay content, as well as bulk
      density compaction, pH, and organic carbon content in soil samples. The
      quantities of N, K, P, Na, Ca, Mg, Fe, Mn, Zn and Cu were determined in all
      herbaceous cover forest floor and soil samples. The quantities of Na, Fe, Zn, Cu
      and Mn in herbaceous understory samples from the skid road were considerably
      higher than those in the undisturbed area, while the quantity of Mg was
      considerably lower. These differences could have been caused by decreased
      herbaceous cover in addition to variations in the properties of the forest floor
      and soil after skidding. A lower amount of forest floor on the skid road was the
      result of skidding and harvesting activities. Mg and Zn contents in forest floor
      samples were found to be considerably lower for the skid road than for the
      undisturbed area. No significant differences were found in soil chemical
      properties (quantities of N, P, K, Na, Ca, Mg, Fe, Zn, Cu and Mn) at the 0-5 cm
      soil depth. Important differences exist between soil quantities of Mg at a 5-10
      cm depth on the skid road and in undisturbed areas. Both 0-5 cm and 5-10 cm soil
      depths, the average penetrometer resistance values for the skid road was higher
      than for the undisturbed area. This result shows that the compaction caused by
      skidding is maintained to depth of 10 cm. Skid road soil showed higher bulk
      density values than undisturbed areas because of compaction.

PMID- 21186724
TI  - Effects of cyanobacterium Microcystis aeruginosa on the filtration rate and
      mortality of the freshwater bivalve Corbicula leana.
AB  - We compared filtering rates (FR) and mortalities between freshwater filter
      feeding bivalve Corbicula leana acclimatized (AM) and non-acclimatized (NAM) to
      an cyanobacterial bloom (mainly Microcystis aeruginosa) over seven days. Both
      mussel populations were simultaneously stocked into mesocosms constructed in
      littoral zones of a eutrophic lake at a density of 740 ind. m(-2) for 16 days.
      NAMs decreased the concentration of chlorophyll-a 50% less than AMs. For the
      first seven days, the FRs (0.46-0.61) and mortality rate (slope = -30.2, r = 
      0.95) of NAMs were higher than those of AMs, possibly due to a sudden increase in
      unselective filtering. From the eighth day NAM mortality decreased rapidly and
      then stabilized, becoming similar to that of AMs through the end of the
      experiment. Stocking both AMs and NAMs increased the NH4-N concentration in the
      water, and the mortality rates of both mussel populations were correlated with
      NH4-N. In contrast, other nutrients and microcystin concentrations were not
      significantly associated with mussel mortality. These results indicate that
      although a sudden introduction of non-acclimatized C. leana may partially control
      phytoplankton biomass fora short period, previous short-term acclimatization is
      needed to minimize mussel mortality.

PMID- 21186725
TI  - Stability of some quality traits in bread wheat (Triticum aestivum) genotypes.
AB  - This study was carried out in order to determine some quality traits such as
      thousand grain weight (TGW), hectoliter weight (HW), grain protein content (GPC),
      Zeleny sedimentation volume (ZSV) and stability of quality traits of 25 bread
      wheat genotypes. The experiment was conducted at seven environmental conditions
      during 2 growing periods (2003-2004 and 2004-2005) using randomized complete
      block design with four replicates. The ANOVA showed that out of the total sum of
      squares, 48.4, 28.0 and 23.6% for TGW, 71.4, 14.9 and 13.7% for HW, 54.4, 23.0
      and 22.6% for GPC, 44.7, 41.7 and 13.6% for ZSV was attributable to E, G and G x
      E interaction effects, respectively. Thousand grain weight, hectoliter weight,
      grain protein content and Zeleny sedimentasyon volume of genotypes changed from
      34.5 to 41.4 g, from 76.5 to 80.4 Kg, from 11.49 to 13.37% and from 22.1 to 46.0
      ml, respectively. Seven stability parameters, covering a wide range of
      statistical approaches, were used so as to predict the genotypes. The study of
      genotypic stability showed that Bezostaya and advanced lines numbered 11 and 24
      had high stability for quality traits and proved to be the best within the pool
      of the studied genotypes. Also, 8 and 17 numbered genotypes demonstrated high
      stability for TGW, HW, GPC and HW, GPC and ZSV, respectively.

PMID- 21186726
TI  - Gas exchange in Paulownia species growing under different soil moisture
      conditions in the field.
AB  - In order to evaluate their responses to drought, we determined the photosynthetic
      activity water potential, stomatal conductance, transpiration, water use
      efficiency photosynthetic photon flux density and leaf temperature of Paulownia
      imperialis, P. fortunei and P. elongata in three different soil moisture
      conditions in the field. Our results showed that P. imperialis had greater
      photosynthesis (8.86 micromol CO2 m(-2) s(-1)) and instantaneous water use
      efficiency (0.79 micromol CO2 mmol H2O(-1)) than either P. elongata (8.20
      micromol CO2 m(-2) s(-1) and 0.71 micromol CO2 mmol H2O(-1)) or P. fortunei (3.26
      micromol CO2 m(-2) s(-1) and 0.07 micromol CO2 mmol H2O(-1)). The rapid growth of
      Paulownia did not appear to be correlated with photosynthetic rates. Paulownia
      fortunei showed more transpiration (48.78 mmol H2O m(-2) s(-1)) and stomatal
      conductance (840 mmol m(-2) s(-1)) than P. imperialis (20 mmol H2O m(-2) s(-1)
      and 540 mmol m(-2) s(-1)) and P. elongata (20 mmol H2O m(-2) s(-1) and 410 mmol
      m(-2) s(-1)), which allowed these two Paulownia species to increase their
      tolerance to low soil moisture, and maintain higher water use efficiency under
      these conditions. According to our physiological gas exchange field tests,
      Paulownia imperialis does appear to be capable of successful growth in semiarid
      zones.

PMID- 21186728
TI  - Effects of spacing and post-planting treatments on survival and growth of
      Fraxinus angustifolia seedlings.
AB  - This study was conducted at a bottomland hardwood site with heavy textured soil
      in Akyazi, Turkey to determine the effect of initial spacing (3.0 x 3.0, 3.0 x
      2.0, 2.5 x 1.6 and 2.5 x 1.2 m) and post-planting treatments (untreated check,
      moving, hoeing, disking, and hoeing plus disking) on early survival and growth of
      Fraxinus angustifolia Vahl. One-year old bare-root seedlings (70 +/- 5 cm in
      height) were hand-planted in December 2004. Through three years survival was
      perfect with a rate of 98% in all treatments. Spacing and the interaction between
      spacing and post-planting treatment did not significantly affect seedling growth
      through three years. However height and diameter growth increased overtime and
      differed significantly among post-planting treatments. The hoeing and hoeing plus
      disking treatments gave the highest growth, and resulted in about 31% increase in
      diameter and height increment, and in total diameter and height about 20%. These
      results suggest that post-planting treatments on bottomland sites with heavy
      textured soil give promising results.

PMID- 21186727
TI  - Nitrogen mineralization in a high altitude ecosystem in the mediterranean
      phytogeographical region of Turkey.
AB  - Interrelations exist in the terrestrial ecosystems between the plant type and
      characteristics of nutrient uptake. Annual net nitrogen mineralization in soils
      of different plant communities in the high altitude zone of Spil mountain located
      in the Mediterranean phytogeographical region of Turkey was investigated
      throughout one year by field incubation method. Seasonal fluctuations resulting
      from field incubation were markedly higher in autumn and spring than summer.
      These are mainly associated with the changes in soil moisture being at minimum in
      the Mediterranean summer. A significant correlation was developed between the net
      Nitrate (kg NO3(-)-N ha week(-1)) production and soil water content (p<0.05; r =
      0.316 in soil of 0-5 cm; r = 0.312 in soil of 5-15 cm). The results showed that
      the annual productivity of nitrogen mineralization shows different values
      depending on communities. Annual net ammonium (NH4(+)-N) production in the soils
      of each community was negatively estimated. However annual net nitrate (NO3(-)-N)
      production (0-15 cm) was higher in grassland (27.8 kg ha y(-1)) and shrub (25.0
      kg ha y(-1)) than forest (12.4 kg ha y(-1)) community. While annual net N(min)
      values were close to each other in grassland (14.5 kg ha y(-1)) and shrub (14.1
      kg ha y(-1)), but negative in forest community (-3.6 kg ha y(-1)). The reasons
      for these differences are discussed.

PMID- 21186729
TI  - Removal of melanoidin present in distillery effluent as a major colorant: a
      review.
AB  - Effluent originating from distilleries contain large amount of dark brown
      coloured wastewater called molasses spent wash (MSW). This MSW is the unwanted
      residual liquid waste to dispose because of low pH, high temperature, dark brown
      colour, high ash content, unpleasant odour and high percentage of organic and
      inorganic matter. Dark brown colour of MSW is due to the presence of melanoidin
      pigment. It reduces sunlight penetration in rivers and lakes which in turn
      decrease both photosynthetic activity and dissolved oxygen concentration
      affecting aquatic life. So the disposal of this effluent is one of the critical
      environmental issues. A number of treatment processes have been employed for the
      distillery waste management. This review paper present an overview of the
      pollution problems caused by melanoidin and the technologies employed globally
      for its removal.

PMID- 21186730
TI  - Biochemical responses and accumulation of cadmium in Spirodela polyrhiza.
AB  - The present study focused on biochemical responses of Spirodela polyrhiza to
      cadmium stresses and its accumulation. The laboratory experiments were conducted
      for the assessment of biochemical responses and accumulation of cadmium in plants
      at its various concentrations (0.1, 0.5, 1.5 and 2.0 ppm) at the regular interval
      for twelve days exposure. Spirodela showed visible symptoms like withering of
      roots and chlorosis at higher concentration (2.0 ppm), however the plant showed
      normal growth at lower concentration (0.1 ppm). The estimation of biochemical
      parameters (total chlorophyll, protein and carbohydrate) of test plants showed a
      significant increase at lower concentration (0.1 ppm) of cadmium. The biochemical
      changes decrease with increase in exposure concentration and duration. The toxic
      effect of cadmium is directly proportional to its concentration and duration. The
      accumulation of cadmium by Spirodela polyrhiza was maximum at four days exposure
      duration and gradually decreases.

PMID- 21186731
TI  - Seasonal variation and diversity of rotifers in Ehoma lake, Nigeria.
AB  - The zooplankton and physicochemistry of Ehoma lake were studied from March 2005
      to August 2006 in order to evaluate seasonal trend in species composition and
      abundance in relation to water quality. Forty two (42) species of rotifers
      dominated by Keratella tropica tropica were encountered. Species richness
      declined by nearly 50% from dry season values during the rainy season. Species
      richness was higher in the littoral zone during the dry season, the reverse was
      the case during the rainy season. Species abundance followed similar trend as
      species richness. Abundance was closely associated with dissolved oxygen,
      biological oxygen demand and width of the lake and these in turn varied
      significantly between seasons. Shannon-Weaver diversity varied from 2.2 to 3.8
      bit ind(-1) and significantly between seasons (p<0.05). Anuraeopsis navicula
      navicula and Euchlanis dilatata dilatata Ehrenbreg were the only species gained
      during the flood periods.

PMID- 21186732
TI  - Infection and immunization trials of Asian seabass (Lates calcarifer) against
      fish pathogen Vibrio anguillarum.
AB  - Vibriosis is one of the most prevalent fish diseases caused by bacteria belonging
      to the genus Vibrio sp. Fish disease will be controlled by proper vaccination
      trials and maintenance of fish form. Pathogenicity for Asian seabass (Lates
      calcarifer) against V anguillarum results in necrosis and haemorrhagic areas near
      the base of fins, exopthalmia and ulcers on the skin surface. Around 50, 100, 200
      microl of formalin killed bacterial cells were injected (Intraperitoneal) to
      three different size (5-10, 20-30, 35-50 g) of seabass fishes respectively and
      control sere as saline were maintained separately. The Relative Percentage
      Survival (RPS) for vaccinated fishes was 60, 75, and 62.5 respectively and the
      vaccinations for 20-30 g fishes stay alive. These results stated that the
      vaccination for fishes with 20-30 g size may fabricate good immune response.

PMID- 21186733
TI  - Macroinvertebrate diversity of Veli and Kadinamkulam lakes, South Kerala, India.
AB  - The diversity and distribution pattern of benthic macroinvertebrates in two
      backwaters viz., Veli and Kadinamkulam of Kerala were assessed using diversity
      indices. The samples were collected once in three months for a period of two
      years from six sampling sites (K1, K2, K3, V1, V2 and V3) and community
      variations were analyzed. Overall, 24 families were identified represented by
      mollusca, annelida and arthropoda (crustaceans and insects). Among this, dominant
      taxon was Mytilidae of molluscan family and site-wise dominance was maximum in
      sites V1 and V2. Richness and abundance were highest in site V2 and lowest in
      site K2. Diversity index ranged from 0.27 (K2) to 2.33 (V1). The diversity and
      distribution patterns of certain species were clearly related to water quality as
      evident from the present study.

PMID- 21186734
TI  - Growth, yield and photosynthesis of Panicum maximum and Stylosanthes hamata under
      elevated CO2.
AB  - Plant height, biomass production, assimilatory functions and chlorophyll
      accumulation of Panicum maximum and Stylosanthes hamata in intercropping systems
      was influenced significantly under elevated CO2 (600 +/- 50 ppm) in open top
      chambers (OTCs). The plant height increased by 32.0 and 49.0% over the control in
      P. maximum and S. hamata respectively in intercropping system under elevated CO2
      over open field grown crops (Ca). P. maximum and S. hamata produced 67 and 85%
      higher fresh and dry biomass respectively under elevated CO2. Rates of
      photosynthesis and stomatal conductance increased in both the crop species in
      intercropping systems under elevated CO2. The canopy photosynthesis
      (photosynthesis x leaf area index) of these crop species increased significantly
      under elevated CO2 over the open grown crops. The chlorophyll a and b
      accumulation were also higher in the leaves of both the crop species as grown in
      OTC with elevated CO2. The increased chlorophyll content, leaf area index and
      canopy photosynthesis led to higher growth and biomass production in these crop
      species under elevated CO2. The total carbon sequestration in crop biomass and
      soils during the three years was 21.53 Mg C/ha under elevated CO2. The data
      revealed that P. maximum and S. hamata intercropping system is the potential as a
      sink for the increasing level of CO2 in the atmosphere in the semi-arid tropics.

PMID- 21186735
TI  - Effects of working memory load and repeated scenario exposure on emergency
      braking performance.
AB  - OBJECTIVE: The objective of the present study was to examine the effect of
      working memory load on drivers' responses to a suddenly braking lead vehicle and
      whether this effect (if any) is moderated by repeated scenario exposure.
      BACKGROUND: Several experimental studies have found delayed braking responses to
      lead vehicle braking events during concurrent performance of nonvisual, working
      memory-loading tasks, such as hands-free phone conversation. However, the common
      use of repeated, and hence somewhat expected, braking events may undermine the
      generalizability of these results to naturalistic, unexpected, emergency braking
      scenarios. METHOD: A critical lead vehicle braking scenario was implemented in a
      fixed-based simulator.The effects of working memory load and repeated scenario
      exposure on braking performance were examined. RESULTS: Brake response time was
      decomposed into accelerator pedal release time and accelerator-to-brake pedal
      movement time. Accelerator pedal release times were strongly reduced with
      repeated scenario exposure and were delayed by working memory load with a small
      but significant amount (178 ms).The two factors did not interact. There were no
      effects on accelerator-to-brake pedal movement time. CONCLUSION: The results
      suggest that effects of working memory load on response performance obtained from
      repeated critical lead vehicle braking scenarios may be validly generalized to
      real world unexpected events. APPLICATION: The results have important
      implications for the interpretation of braking performance in experimental
      settings, in particular in the context of safety-related evaluation of in-vehicle
      information and communication technologies.

PMID- 21186736
TI  - Joint kinetics and muscle activity while walking on ballast.
AB  - OBJECTIVE: This study examined the impact of two common sizes of ballast on gait
      biomechanics. The terrain was designed to simulate a railroad work setting to
      investigate the variation in gait kinetics and muscle activation while walking.
      BACKGROUND: Research and epidemiology suggest a potential link between walking
      surface characteristics and injury. However, few studies have investigated the
      impact of ballast surfaces, which is a surface of interest in the railroad and
      construction industries, on gait dynamics. METHOD: For this study, 20 healthy
      adult men walked along three distinct pathways (no ballast [NB], walking ballast
      [WB], and mainline ballast [MB]). WB and MB consisted of rock with an average
      size of 0.75 to I in. and 1.25 to 1.5 in., respectively. Full-body motion, ground
      reaction forces, and electromyographic (EMG) signals from lower extremity muscles
      were collected, and three dimensional joint moments were calculated. Parameters
      of interest were moment trajectories and ranges, EMG activity, and temporal gait
      measures. RESULTS: Joint-specific differences indicate significant variations
      between surface conditions. Joint moment ranges were generally smaller for MB and
      WB compared with NB. EMG activity, in particular, co-contraction levels, was
      found to be significantly greater on ballast compared with NB. Temporal gait
      parameters were significantly different for MB than for either WB or NB.
      CONCLUSION: Walking on ballast increases muscle activation to control the moments
      of the lower extremity joints. APPLICATION: The results suggest that ballast has
      an effect on muscles and joints; thus, the findings provide insight to improve
      and develop new work practices and methods for injury prevention.

PMID- 21186737
TI  - User-preferred position of computer displays: effects of display size.
AB  - OBJECTIVE: Effects of display size and dual display setting on preferred display
      and keyboard positions were evaluated. BACKGROUND: User-preferred display
      position may vary as its size changes or when multiple displays are used. It is
      also not known whether the use of larger displays or multiple displays would
      influence positioning of the keyboard. METHOD: Participants (N=19) who had normal
      visual acuity (20/30 or better) determined preferred positions of the display and
      the keyboard during a data entry task in four display setups (19, 24, 27.5, and
      dual 19 in.). The size of capital characters (3.2 mm high) was kept consistent
      between setups. RESULTS: Preferred viewing distance ranged from 0.68 m (19-in.
      display) to 0.76 m (27.5-in. display). No significant differences in viewing
      distance and display height were found between the single 19-in. display and dual
      19-in. displays setups. The preferred position of the keyboard was consistent
      between display setups. CONCLUSION: Participants placed larger displays farther
      and lower while maintaining the display top at or near eye height. Preferred
      position of the dual displays in landscape setting did not differ from that of a
      single display. It appears that the preferred display position varies with the
      vertical dimension of the overall viewable area of the display. APPLICATION: The
      results of this study can be used to determine the dimensions or adjustability of
      computer workstations for larger displays or multiple displays settings.

PMID- 21186738
TI  - An investigation of the prevalence of replication research in human factors.
AB  - OBJECTIVE: The present studies investigated the nature of replication research
      within the human factors literature. BACKGROUND: Many claim that researchers in
      certain fields do not replicate prior research. This is troubling because
      replications allow science to self-correct. A successful replication corroborates
      the original finding, whereas an unsuccessful replication falsifies it. To date,
      no one has assessed whether this issue affects the field of human factors.
      METHOD: In the first study, eight articles (parent articles) were selected from
      the 1991 issues of the journal Human Factors. Each article that had referenced
      one of the eight parent articles between 1991 and September 2006 (child articles)
      were also retrieved. Two investigators coded and compared each child article
      against its 1991 parent article to determine whether the child article replicated
      its parent article. The second study replicated these procedures. RESULTS: Half
      or more of the parent articles in Study I and Study 2 (75% and 50%, respectively)
      were replicated at least once. Furthermore, human factors researchers conducted
      replications of their own work as well as the work of others. However, many
      researchers did not state that they replicated previous research. CONCLUSION:
      Replications seem to be common in the human factors literature. However, readers
      may not realize that a study replicated prior research. Thus, they may
      incorrectly assess the evidence concerning a given finding. APPLICATION: Human
      factors professionals should be taught how to identify replications and to be
      cautious of research that has not been replicated.

PMID- 21186739
TI  - Demonstration-based training: a review of instructional features.
AB  - OBJECTIVE: This article reviews instructional features used in demonstration
      based training (DBT). BACKGROUND: The need for fast and effective training and
      performance support that can be accessed from anywhere is a growing need for
      organizations. DBT programs are one method to address these needs, but a better
      understanding of how to maximize the effectiveness of DBT activities is needed.
      Specifically, beyond the content of the demonstration (i.e., the dynamic example
      of task performance), what instructional features (i.e., information and
      activities in addition to the demonstration) can be used to improve the
      effectiveness of DBT interventions? METHOD: The authors conducted a systematic
      review of the applied and basic science literatures relevant to DBT. RESULTS:
      Instructional features in DBT can be categorized according to the degree to which
      they encourage active learner involvement (i.e., active vs. passive), when they
      occur relative to viewing the demonstration (i.e., pre-, during-, and
      postdemonstration conditions), and the observational learning process they are
      intended to augment. Five categories of instructional features are described:
      passive guidance or support, preparatory activities, concurrent activities,
      retrospective activities, and prospective activities. CONCLUSION: There is a wide
      variety of instructional features used in DBT, but more systematic research is
      needed to understand the conditions under which each is most effective as well as
      to outline a method for sequencing of demonstration with other delivery methods,
      such as practice opportunities. APPLICATION: The framework presented in this
      article can help guide the systematic development of training systems
      incorporating DBT as well as provide a direction for future research.

PMID- 21186740
TI  - Meaningful misuse of electronic health records.

PMID- 21186741
TI  - Medicare's proposed CY 2011 physician payment rule--keep watch!

PMID- 21186742
TI  - And now, a post-election preview.

PMID- 21186743
TI  - IMS hits all-time membership high.

PMID- 21186744
TI  - On the right track at the UI Carver College of Medicine.

PMID- 21186745
TI  - Iowa Healthcare Collaborative celebrates five years.

PMID- 21186746
TI  - Revisiting empathy.

PMID- 21186747
TI  - Partial breast irradiation: the new standard of care for women with early breast
      cancer?

PMID- 21186748
TI  - Where do people with lung cancer die and how is this changing? A population-based
      study.
AB  - Investigating trends in where cancer patients die may help inform decisions about
      how healthcare should be organised to support those in need of end-of-life care.
      We analysed time trends in place of death for lung cancer during 1994-2005, based
      on 18,078 death certificates. Time trends were analysed by joinpoint regression.
      9,485 (53%) deaths occurred in an acute hospital, 5,239 (29%) at home, 2,178
      (12%) in hospices and 728 (4%) in nursing homes. Hospice deaths rose from 7%
      (108/1539) in 1994 to 15% (234/1560) in 2003, falling slightly in 2004-05.
      Hospital deaths were unchanged over time, but were more common in areas without
      hospices. Home deaths decreased significantly (annual percentage change (APC)=
      2.2%, 95%CI -3.0% to -1.3%). Nursing home deaths rose significantly (APC=5.7%,
      95%CI 2.5% to 8.9%). These trends were not explained by temporal changes in the
      age-sex distribution of deaths. Despite evidence suggesting most cancer patients
      would prefer to die at home, and developments in palliative care services, home
      deaths are declining and most lung cancer deaths occur in hospital.

PMID- 21186749
TI  - Antenatal management of the expectant mother and extreme preterm infant at the
      limits of viability.
AB  - We explored the opinions of healthcare providers on the antenatal management and
      outcome of preterm delivery at less than 28 weeks gestation. An anonymous postal
      questionnaire was sent to health care providers. The response rate was 55% (74%
      Obstetrician, 70% neonatologist). Twenty four weeks is the limit at which most
      would advocate intervention. At 23 weeks 67% of neonatologists advocate antenatal
      steroids. 50% of all health care providers advocate cardiotocographic monitoring
      at 24 weeks gestation. Written information on survival and long-term outcome is
      provided by 8% of the respondents. Neonatologists (50%) were more likely than
      obstetrician (40%) to advocate caesarean section at 25 weeks. We conclude that 24
      weeks is the limit at which most would advocate intervention. Significant
      variation exists both between and within each health care group at less than 25
      weeks. Establishment and provision of national outcome data may aid decision
      making at the limits of viability.

PMID- 21186750
TI  - Thromboembolism prophylaxis practices in orthopaedic arthroplasty patients.
AB  - Thromboembolic events are a post-operative complication of arthroplasty surgery
      for up to 3 months. The incidence however, is not fully known. Some form of
      prophylaxis should be provided to all arthroplasty patients. Clinicians are wary
      of side effects, compliance profile and the associated cost. The objective of
      this study is to investigate practice patterns and their relevance to 3 risk
      groups. Ninety questionnaires were sent to orthopaedic surgeons with 3
      hypothetical clinical scenarios and 10 prophylaxis regimes for thromboembolism
      across different risk groups. The response rate was 81/90 (90%). The most popular
      options in all 3 cases were early mobilisation, thrombo-embolism deterrant (TED)
      stockings and low molecular weight heparin (LMWH) (51/81, 62% of all cases). An
      inconsistent relationship exists between preferred practice and relevant
      guidelines. Preferred practice does not correlate with each level of risk.

PMID- 21186751
TI  - Spontaneous pneumothorax management.
AB  - Guidelines for the management of spontaneous pneumothorax were published by the
      British Thoracic Society (BTS) in 2003. The aim of our study was to assess
      compliance with the BTS guidelines. A retrospective review was performed on all
      spontaneous pneumothoraces admitted to our hospital between June 2006 and
      December 2007. There were 29 pneumothoraces during the study period, 20 of which
      were primary spontaneous pneumothoraces (PSPs). All 15 (100%) large PSPs had an
      intercostal drain (ICD) inserted with a mean calibre of 20Fr, however only 1 of
      the 15 (6.7%) had a prior attempt at aspiration. High flow oxygen was used in
      3/20 (15%) PSPs and 1/9 (11%) secondary spontaneous pneumothoraces (SSPs). 5/6
      (83%) of large SSPs had ICDs placed with a mean calibre of 23.3Fr. Compliance
      with BTS guidelines was suboptimal. In particular, simple aspiration was
      underutilised with an over-reliance on unnecessary tube thoracostomy. Moreover,
      the calibre of intercostal drains used was in excess of BTS recommendations. This
      study highlights the need to formally adopt BTS guidelines, thereby establishing
      a more standardised practice which should improve management of spontaneous
      pneumothoraces.

PMID- 21186752
TI  - Oral health of children born small for gestational age.
AB  - We sought to evaluate the oral health status of children born small for
      gestational age (SGA). Children now aged 4-8 years who were born SGA (birth
      weight < -2 SDS) were examined using standardised criteria. The parents completed
      a structured oral health questionnaire. Twenty females and 25 males, mean age
      72.1 months, and mean birth weight 2.1 kg, participated in the study. Poor
      appetite was a concern; 32 (71%) children snacked between meals and 14 (30%) used
      carbonated beverages more than 3 times daily. Erosion was present in 9 (20%)
      children. Dental decay occurred in 22 (47%) children with 92% being untreated.
      Eight children had more than 5 decayed teeth. It is essential that clinicians
      working with children born SGA include oral health within the general health
      surveillance and refer these children for a dental assessment within the first 2
      years to support parents in establishing safe feeding patterns for their
      children.

PMID- 21186753
TI  - Smoking prolongs the infectivity of patients with tuberculosis.
AB  - We sought to establish if smokers on anti-tuberculosis treatment are more likely
      to have a prolonged period of infectivity, compared to non-smoking tuberculosis
      patients, in a low tuberculosis prevalence country. We conducted a cross
      sectional, retrospective study in Ireland that recruited 53 microbiologically
      confirmed cases of pulmonary tuberculosis (PTB). The age-sex adjusted odds ratios
      (AOR) suggest that the infectivity status of PTB on treatment was four times more
      likely to be prolonged beyond 6-8 weeks, if the cases had a smoking history (AOR:
      4.42; 95% CI: 1.23; 15.9). Smoking was associated with delayed sputum smear
      conversion in PTB patients on treatment.

PMID- 21186754
TI  - Impact of pharmacotherapy on the incidence of transurethral prostatectomy for
      benign prostatic hyperplasia and the implications for surgical training.
AB  - Medical therapy has become first line treatment for Benign Prostatic Hypertrophy
      (BPH) and in many cases TURP may no longer be required. Proof and quantification
      of this evolution in practice has been somewhat elusive and provided the
      principle impetus for this study. This is a retrospective study of BPH management
      in Republic of Ireland from 1995 to 2008. National treatment databases were
      sourced for numbers undergoing TURP and pharmacotherapy prescribing data was
      obtained from individual pharmaceutical companies. A total of 28,240 TURP's were
      performed nationally between 1995 and 2008. TURP's performed annually, decreased
      by 1,494 (51%), alpha-blocker prescriptions increased from 8,710 to 302,159 units
      and the number of urology trainees increased by 10 (60%). Clear association
      between decreases in TURP's and increases in pharmacotherapy for BPH is
      demonstrated. Implications on training likely exist and will require proper
      evaluation in order to maintain future standards in this surgical practice.

PMID- 21186755
TI  - Re: Is hospital based MMR vaccination for children with egg allergy here to stay?

PMID- 21186756
TI  - Sticking to the rules: are you documenting your Irish Medical Council
      Registration Number?

PMID- 21186757
TI  - Acute methaemoglobinaemia secondary to intentional dapsone overdose.

PMID- 21186758
TI  - Varenicline (champix)-associated manic relapse in bipolar affective disorder.

PMID- 21186759
TI  - Potential risk of exposure to selected xenobiotic residues and their fate in the
      food chain--part I: classification of xenobiotics.
AB  - Consumers are exposed to a diversity of chemicals in all areas of life. Air,
      water, soil and food are all unavoidable components of the human environment.
      Each of those elements influences the quality of human life, and each of them may
      be contaminated. We are exposed to toxic or potentially toxic compounds in many
      ways in our daily lives and toxicology is clearly a subject of great importance
      for society. This becomes apparent when we look at the types of poisons and the
      ways in which we are exposed to them. Indeed, the categories cover virtually all
      the chemicals one might expect to encounter in the environment. After
      consideration of this, one might well ask "Are all chemicals toxic?" Phrase as an
      answer: "There are no safe chemicals, only their safe use". Xenobiotics are
      defined here as those compounds, both organic and inorganic, produced by human
      beings and introduced into the environment, as well as into the food chain at
      concentrations that cause undesirable effects. Xenobiotics in the food chain are
      monitored in two forms: by testing--the objective of which is to discover
      unsuitable foodstuffs in the consumer's network, and by monitoring--to obtain
      objective information about environmental components contamination and to
      harmlessness health of available foodstuffs.

PMID- 21186760
TI  - Endotoxins and beta-glucans as markers of microbiological contamination-
      characteristics, detection, and environmental exposure.
AB  - Endotoxins and beta-glucans are one of the major markers of microbiological
      contamination. As components of biological aerosols, they are ubiquitous in many
      environments. Numerous studies performed during the last three decades have
      proved that exposure to endotoxins and beta-glucans could be associated with many
      diseases and/or adverse health outcomes. The aim of this review is to present the
      current stage of knowledge regarding endotoxins and beta-glucans as biologically
      active components of aerosols and to characterize the quantitative methods for
      their detection in environmental samples. The problems of occupational exposure
      to both these components and their control procedures are also discussed. An
      overview of the available worldwide and Polish standards and threshold limit
      values is also given.

PMID- 21186761
TI  - Environmental exposure of pregnant women to infection with Toxoplasma gondii-
      state of the art.
AB  - Infection with T. gondii is particularly dangerous for pregnant women as it may
      lead to the transplacental passage of the parasite. Currently, congenital
      toxoplasmosis is the second most frequent intrauterine infection. The risk of
      transmission of T. gondii to the foetus varies throughout the world and ranges
      from 0.6-1.7/1,000 of pregnant women. The consequences of congenital
      toxoplasmosis are multifarious. On the basis of current literature review, the
      authors discuss the epidemiological and clinical aspects of toxoplasmosis in
      pregnant women, the influence of climatic and environmental factors that may lead
      to an increase in T. gondii infections in humans, particularly in pregnant women,
      and the principles of prophylactics against T. gondii infections in those women.

PMID- 21186762
TI  - Regulatory strategies to ensure food and feed safety in Poland--update review.
AB  - The principal State authorities responsible for food safety in Poland are
      primarily the national Chief Sanitary Inspectorate followed by the Chief
      Veterinary Inspectorate, who are both statutorily empowered to discharge their
      functions within their competencies defined by the regulations. This article
      presents the current status of legislation in the area of food safety together
      with a description of how systems governing this field are organised in Poland.
      It should be noted that the surveillance and monitoring of food safety covers the
      entire food chain. Also outlined is the way the RASFF system operates in Poland,
      including its track record of experience up to the present time as well as how
      the role of EFSA is integrated into these areas.

PMID- 21186763
TI  - Environmental risk factors for respiratory symptoms and childhood asthma.
AB  - The presented cross-sectional study, comprised a group of 1,130 children from 13
      15 years of age living in Upper Silesia, Poland, was undertaken to ascertain the
      role of environmental factors in the development of adverse respiratory health
      outcomes. To estimate the prevalence of these effects, the ISAAC questionnaire
      supplemented by questions related to risk factors was used. Bronchial asthma was
      identified in 4.5% of the children, asthma diagnosed by physicians in 8.7%, and
      prevalence of wheezing in the previous 12 months in 12.6%. The highest
      probability of wheezing was found in children with maternal genetic propensity
      (such as asthma, allergy), exposed to maternal smoking, or was connected with
      household risk factors such as the presence of dampness/mould or living in 50
      year-old building. Female gender and attendance at nursery school were shown to
      be protective factors against wheezing. The probability of asthma was nearly
      twice as high in children residing in damp/mouldy dwellings, heated by coal-fired
      furnaces and living in the immediate vicinity of a road with heavy traffic. This
      study revealed that exposure to indoor (tobacco smoke, coal stove emission, mould
      or dampness in dwelling) and outdoor (traffic pollution) air contaminants are
      major environmental factors responsible for adverse respiratory health effects in
      children.

PMID- 21186764
TI  - Level of DNA damage in lead-exposed workers.
AB  - Lead plays a significant role in modern industry. This metal is related to a
      broad range of physiological, biochemical and behavioural dysfunctions. The
      genotoxic effects of lead have been studied both in animals and humans in in
      vitro systems but results were contradictory. The aim of this study was to
      investigate the association between DNA damage and occupational exposure to lead
      in workers. The study population consisted of 62 employees of metalworks exposed
      to lead in the southern region of Poland. The control group consisted of 26
      office workers with no history of occupational exposure to lead. The
      concentration of lead (PbB) and zincprotoporphyrin (ZPP) in blood samples were
      measured. The DNA damage was analyzed in blood lymphocytes using alkaline comet
      assay. The level of DNA damage was determined as the percentage of DNA in the
      tail, tail length and tail moment. The lead exposure indicators were
      significantly higher in lead exposed group: PbB about 8.5 times and ZPP 3.3
      times. Also, the percentage of DNA in the tail (60.3 +/- 14 vs. 37.1 +/- 17.6),
      comet tail length (86.9 +/- 15.49 vs. 73.8 +/- 19.12) and TM (57.8 +/- 17.82 vs.
      33.2 +/- 19.13) were significantly higher in the study group when compared with
      the controls; however, the difference between the subgroups was only 5-10%. Years
      of lead exposure positively correlated with all comet assay parameters (R = 0.21
      0.41). Both mean and current PbB and ZPP were correlated with tail DNA % and TM
      (R = 0.32; R = 0.33; R = 0.24; R = 0.26 and R = 0.34; R = 0.33; R = 0.28 and R =
      0.28, respectively). This study shows that occupational exposure to lead is
      associated with DNA damage and confirmed that comet assay is a rapid, sensitive
      method suitable for biomonitoring studies.

PMID- 21186765
TI  - Parasitisation and localisation of ticks (Acari: Ixodida) on exotic reptiles
      imported into Poland.
AB  - As a result of examinations, the following species of ticks have been found
      parasitising on Python regius brought from Africa to Poland: Amblyomma latum,
      Amblyomma transversale, Amblyomma spp., on Varanus exanthematicus: Amblyomma
      exornatum, Amblyomma flavomaculatum, Amblyomma latum, Amblyomma nuttalli,
      Amblyomma spp., on Varanus salvator brought from Indonesia to Poland: Amblyomma
      varanensis. There were 58 specimens of monitor lizard (V. salvator and V.
      exanthematicus) and 92 specimens of python (P. regius) examined, with the
      selected locations of parasitisation by the ticks on the host's body described in
      detail. Among the 434 specimens of tick collected from the monitor lizards, the
      majority parasitised the host's limbs (40.5%), on the trunk (29.3%), the head
      (20.3%), and least on the tail (9.9%). There were 430 tick specimens collected
      from the bodies of the pythons. They chiefly parasitised the whole length of the
      back (54.4%) and on the abdominal side of the trunk (29.8%), less numerously in
      the neighbourhood of the cloaca (5.6%), around the eyes (3.7%), in the nasal
      openings (0.9%) and the remaining parts of the head (5.6%). Examination of the
      ticks' location on the reptiles' bodies enabled us to discover the specific
      parasitisation locations of ticks along the entire length of the host's body.
      Knowledge of the ticks' location on the bodies of specific reptile species,
      particularly at a time when the import of exotic animals is growing all over the
      world, will help in drawing up methods of fighting the parasites, and may give
      valuable clues to veterinary services and private breeders.

PMID- 21186766
TI  - Assessment of annual exposure of private farmers to whole body mechanical
      vibration on selected family farms of plant production profile.
AB  - The objective of the study was evaluation of an annual exposure of private
      farmers to whole body mechanical vibration on selected family farms of plant
      production profile. The study covered 15 family farms, using arable land of the
      size of 10-50 ha (22.3 ha on average), engaged mainly in plant production, and
      equipped with tractors, tractor-mounted agricultural machinery, with a partial
      contribution of self-propelled machines. The scope of the study covered the
      carrying out of time schedules of agricultural activities, and measurements of
      effective values (RMS) for vibration acceleration (equivalent), frequency
      corrected, on the seats of farm vehicles in 3 spatial directions of vibration (X,
      Y, Z). The measurements were made while performing various basic field and
      transport work activities during the period of the whole year. The study showed
      (plant production) that the degree of whole body mechanical vibration load among
      farmers during the whole year depends on the vibration level and duration of
      exposure to this factor. The highest values of the total vibration dose (d) occur
      both during summer-autumn months (August, September, October and November), and
      in spring (April, May). The mean equivalent of daily vibration acceleration shows
      the highest values during 4 months of the year: April and May (0.52 m/s(2)), and
      in August and September (0.56-0.57 m/s(2)); the average value of this parameter,
      for the whole year, reaches the level of 0.45 m/s(2). Considering the fact of the
      occurrence of mechanical shocks in agricultural vehicles (high maximum
      accelerations values registered: 0.81-1.01 m/s(2); standard exceeding), and
      exceeding of the daily exposure action value, proper steps should be undertaken
      with respect to the protection of private farmers against risk resulting from
      exposure to mechanical vibration while performing work activities.

PMID- 21186767
TI  - Predictors of sick leave owing to neck or low back pain: a 12-year longitudinal
      cohort study in a rural male population.
AB  - Back pain is a common cause of sick leave. We analyzed how individual, work
      related and lifestyle factors predicted sick leave owing to neck or low back pain
      over a 12-year period. In this prospective cohort study, 1,405 rural middle-aged
      farmers and non-farmers were surveyed in 1990-1991 (participation rate 76%) and
      followed up 12 years later (participation rate 68%). The 836 men who reported
      having experienced unspecific neck or low back pain the year prior to survey 1
      were followed up for self-reported sick leave owing to neck or low back problems.
      Individual, occupational and lifestyle factors and data on acquired specific neck
      or back diagnosis were included in multiple logistic regression models. Seven
      percent reported neck or low back related sick leave during the 12 year period.
      Self-employment was associated with a lower risk of sick leave while sedentary
      leisure time, snuff use and a specific neck or back diagnosis was associated with
      a higher risk. Age, education, physical workload, marital status, sense of
      coherence, smoking, and alcohol consumption were not independently associated
      with sick leave. The low risk of sick leave among the self-employed is notable
      from a societal and public health perspective.

PMID- 21186768
TI  - Decrease in ambient air lead concentrations in Varna, Bulgaria, associated with
      the introduction of unleaded gasoline.
AB  - An examination of ambient air lead monitoring data was used to demonstrate
      success of banning the import and use of leaded gasoline in Bulgaria. From 1996
      2007 air lead levels in Varna, the third largest city, decreased up to 63-fold.

PMID- 21186769
TI  - Exposure, symptoms and airway inflammation among sewage workers.
AB  - The purpose of the study was to determine the associations between dust,
      endotoxins and bacterial exposure, and health effects in sewage workers. Exposure
      of 19 workers handling dry sludge and 25 other sewage workers was measured.
      Controls were office workers from compost and sewage plants. Spirometry, acoustic
      rhinometry and nitric oxide in exhaled air were performed before and after
      exposure were measured. CRP was measured in blood samples. It was found that
      workers handling dry sludge were exposed to higher levels of dust and endotoxins
      than other workers and reported more airway and systemic symptoms than controls.
      Compared to controls, FEV(1)/FVC was 0.12 lower in workers handling dry sludge
      and 0.05 lower in other sewage workers. Nose irritation, cough and headache were
      more prevalent in workers handling dry sludge (ORs 2.3-23), and together with
      unusual tiredness associated with endotoxins and/or dust, ORs 2.9-34 for-10-fold
      increases in exposure. Cross-shift decreases of nasal dimensions were larger in
      workers handling dry sludge than controls and were associated with dust and
      endotoxin exposure. It was concluded that workers handling dry sludge were higher
      exposed to endotoxins and dust than other sewage workers and also reported more
      respiratory and systemic symptoms. Exposure-response relationships were found for
      nasal dimensions, nose irritation and systemic symptoms.

PMID- 21186770
TI  - Intradiurnal variations of allergenic tree pollen in the atmosphere of Toledo
      (central Spain).
AB  - To study the impact of inhaling airborne pollen on health, it is important to
      know not only their average daily concentrations but also the intradiurnal
      behaviour of these biological particles. This study reports the bi-hourly
      distribution of the arboreal airborne pollen types more abundant in the
      atmosphere of Toledo (central Spain), many of them triggering important allergic
      processes in Toledo citizens and tourist visitors. Knowledge of bi-hourly pattern
      atmospheric variation pollen may help pollinosis patients to adopt preventive
      measures and plan their outdoor activities accordingly. Intradiurnal variation
      has been studied for the arboreal pollen types: Cupressaceae, Fraxinus, Olea,
      Platanus, Populus, Quercus and Ulmus, during the period 2005-2008. The main
      hourly pollen concentrations were observed during sunlight hours and the maximum
      pollen values obtained at midday and in the afternoon, except for pollen types
      Quercus and Platanus, whose maximum pollen concentrations were obtained during
      the night. The statistical analyses performed to compare pollen concentration and
      main hourly meteorological variables proved to be significant for most of the
      taxa. The results show a significant and positive effect of temperature, solar
      radiation and wind speed on the daily variability undergone by atmospheric
      pollen. Relative humidity influenced in a negative way on the intradiurnal
      variation of pollen in the atmosphere of Toledo.

PMID- 21186771
TI  - Prevalence of tick-borne encephalitis virus (TBEV) in samples of raw milk taken
      randomly from cows, goats and sheep in eastern Poland.
AB  - A total of 119 unpasteurized milk samples taken from 63 cows, 29 goats and 27
      sheep bred on 8 farms situated on the territory of the Lublin province (eastern
      Poland), an area of risk of tick-borne encephalitis (TBE), were examined for the
      presence of RNA of tick-borne encephalitis virus (TBEV) by the nested RT-PCR
      method. Milk samples were also tested for the presence of anti-TBEV antibodies by
      ELISA test. By RT-PCR, the greatest prevalence of TBE virus was found in the milk
      of sheep (22.2%), followed by milk of goats (20.7%) and cows (11.1%). By ELISA,
      the greatest prevalence of anti- TBEV antibodies was found also in the milk of
      sheep (14.8%), followed by milk of cows (3.2%) and goats (0%). The results
      suggest a potential risk of infection with TBEV by drinking raw milk on endemic
      areas of TBE, and indicate a need for milk pasteurization before consumption.

PMID- 21186772
TI  - Selected social and health problems in functioning of disabled rural and urban
      inhabitants in the Lublin Region--similarities and differences.
AB  - The objective of the study was determination of the frequency of occurrence of
      selected difficulties associated with disability and social problems which
      disturb the functioning of the disabled in rural and urban areas in the Lublin
      Region. The study was conducted by trained surveyors with the use of a
      standardized questionnaire which covered: 1) Demographic data: age, gender,
      education level and marital status; 2) Information concerning biological and
      legal disability, degree of disability, its causes, functional limitations due to
      disability; 3) Information pertaining to difficulties and barriers in daily
      living of the disabled population. The study covered 403 disabled selected by the
      method of targeted sampling--147 rural and 256 urban inhabitants. Log-linear
      model was applied for data analysis. Unfavourable demographic characteristics of
      the population of the disabled in the study: mean age 63; high percentage of
      never-married males and females; respondents possessing elementary education
      level; dominant number of those occupationally inactive. The most frequent
      limitations associated with disability: limitations in performing household jobs
      (70.9%), walking difficulties (68.1%). High intensity of material difficulties,
      in association with low education level and high percentage of those
      occupationally inactive, are the evidence of socio-economic deprivation of the
      population examined. Differences between rural and urban inhabitants was found:
      in the rural environment, compared to urban areas, the following were more
      frequently reported: lack of possibilities of rehabilitation in the place of
      residence, difficulties with access to medical specialist; alcohol abuse in the
      family, and family disagreements. Urban population more often than rural
      inhabitants perceived loneliness and isolation from the closest family.

PMID- 21186773
TI  - Volatile profiles of toxigenic and non-toxigenic Aspergillus flavus using SPME
      for solid phase extraction.
AB  - Toxigenic and atoxigenic strains of Aspergillus flavus were grown on potato
      dextrose agar (PDA) and wetted (23% moisture) sterile, cracked corn for 14 and 21
      days, respectively. Volatile compounds produced by A. flavus, as well as those
      present in the PDA controls and sterile cracked maize, were collected using solid
      phase micro-extraction (SPME) and identified by gas chromatography/mass
      spectrometry. Results show that growth substrate had a major impact on the number
      and type of volatiles detected. Growth on sterile cracked maize produced many
      more volatiles than did potato dextrose agar. There were also differences
      observed in the type of volatiles produced between toxigenic and non-toxigenic
      isolates, as well as between isolates of the same toxigenic grouping.

PMID- 21186774
TI  - Co-infection with Borrelia species and other tick-borne pathogens in humans: two
      cases from Poland.
AB  - Co-infection with Borrelia species and Anaplasma phagocytophilum or Babesia spp.
      was assessed in a retrospective study of tick-exposed individuals from
      southeastern Poland. The co-infection rate of these pathogens was found to be
      rather low (Borrelia spp./Anaplasma phagocytophilum--4.2%, 1/24; Borrelia
      spp./Babesia spp.--4.2%, 1/24). However, due to the increased prevalence of
      Borrelia spp. in Ixodes ricinus ticks in Poland and the recent emergence of new
      tick-borne infections, it is necessary to carefully evaluate the true risk of
      human infection with several pathogens using more sensitive and reliable
      diagnostic tools. This is the first report of human infection with Babesia spp.
      in Poland that has been confirmed by molecular techniques with homology of 98.9%
      to B. divergens or Babesia EU1.

PMID- 21186775
TI  - Food-dependent exercise-induced anaphylaxis-sequence of causative factors might
      be reversed.
AB  - We present a case of a 27-years-old female who experienced several episodes of
      food-dependent exercise-induced anaphylaxis (FDEIA). Besides two typical episodes
      of FDEIA triggered by a postprandial physical exercise, she also experienced
      atypical episodes in which the sequence of the causative stimuli was clearly
      reversed-clinical symptoms which appeared after a prolonged exercise, followed by
      ingestion of the sensitizing food. This unusual clinical picture entitled us to
      extend the routine recommendations- avoidance of the coincidence of food
      allergens intake and exercise accordingly to her history.

PMID- 21186776
TI  - Orofacial symptoms related to boreliosis--case report.
AB  - Lyme disease (borreliosis) is an infectious disease caused by the Borrelia
      spirochaetes, usually transmitted to humans by the Ixodes ticks. It is manifested
      by a wide spectrum of clinical symptoms varying according to the time elapsed
      from the infection. The paper describes orofacial symptoms of the disease in a
      woman who has suffered from a chronic borreliosis for 3 years. Multiorgan
      clinical manifestations of borreliosis might occur in the masticatory organ and
      this fact should be taken into consideration in the differential diagnosis of
      pain by medical and dental practitioners.

PMID- 21186777
TI  - Serological study of Q fever in sheep in the territory of Eastern Slovakia.
AB  - Q fever is a zoonosis caused by infection with Coxiella burnetii. Although the
      reservoir of C. burnetii consists of various species, the most common sources of
      human infection are farm animals, such as cattle, goats, and sheep. The agent is
      typically transmitted by the aerosol route, and in more than half of the cases
      primary infection is symptomless. Clinical outcomes of C. burnetii infection in
      domestic ruminants consist of abortion and stillbirths in sheep and goats, while
      in cattle it causes infertility and mastitis. A serological survey for C.
      burnetii was undertaken on a population of sheep. A total of 269 sheep serum
      samples were collected and tested for the detection of antibodies against C.
      burnetii phase I and II antigens using an enzyme-linked immunosorbent assay. The
      herd investigated was tested twice, i.e. in 2000 and 2009, to detect the changes
      in seroprevalence. In the first year of investigation, the prevalence of
      antibodies against C. burnetii phase II antigen was estimated at 37.22% and ten
      years later at 58.42%. Antibodies against phase I antigen were not detected in
      any examined serum samples. The difference in seroprevalence after ten years of
      observation was significant (p = 0.001).

PMID- 21186779
TI  - Self-reported methicillin-resistant Staphylococcus aureus infection in USA pork
      producers.
AB  - Pork producers selected from the National Pork Board's producer database were
      surveyed. Five (3.7%) reported being diagnosed with a MRSA infection. Risk
      factors related to swine farm biosecurity were examined. None were statistically
      significant predictors of MRSA infection.

PMID- 21186778
TI  - Endotoxin and beta-(1,3)-glucan levels in automobiles: a pilot study.
AB  - Exposure to bacterial endotoxin and fungal beta-(1,3)-glucan in the indoor
      environment can induce respiratory symptoms. Automobiles are an exposure source
      of allergens but it is not known if, and how much exposure there is to endotoxin
      and fungal beta-(1,3)-glucan. The objective of the study was to determine whether
      automobiles are a potential source of exposure to these microbial products. Dust
      was sampled from the passenger seats of 40 automobiles. Specific Limulus
      amoebocyte kinetic assays were used to measure endotoxin and beta-(1,3)-glucan,
      respectively. Endotoxin and beta-(1,3)-glucan was detected in all samples ranging
      from 19.9-247.0 EU/mg and 1.6-59.8 MUg/g, respectively. There were no significant
      differences in endotoxin levels between automobiles of smokers and non-smokers,
      but beta-(1,3)-glucan levels were about two-fold higher in the automobiles of non
      smokers. In conclusion, endotoxin and beta-(1,3)-glucan exposure in automobiles
      at levels found in our study may be of importance for asthmatics.

PMID- 21186780
TI  - Formation of carcinogenic 4(5)-methylimidazole in Maillard reaction systems.
AB  - 4(5)-Methylimidazole has received the attention of federal and state regulatory
      agencies because of its carcinogenicity and common presence in foods and
      beverages. In the present study, the formation of 4(5)-methylimidazole in
      Maillard reaction model systems consisting of D-glucose/NH(3), L-rhamnose/NH(3),
      methylglyoxal/NH(3), and methylglyoxal/formaldehyde/NH(3) was investigated. 4(5)
      Methylimidazole was formed at levels ranging from 0.49 to 0.71 mg/mL in the d
      glucose/NH(3) model system. The formation of 4(5)-methylimidazole was slightly
      higher in the L-rhamnose/NH(3) system (0.91 mg/mL) than in the d-glucose/NH(3)
      system (0.71 mg/mL) under the conditions used in the present study. A
      methylglyoxal/NH(3) system produced significantly higher levels of 4(5)
      methylimidazole (5.70 mg/mL), suggesting that methylglyoxal is an important
      precursor of 4(5)-methylimidazole. Ammonolysis of methylglyoxal, which is one of
      the glucose degradation products, was proposed to form formamide, which
      subsequently reacted with 2-aminopropanal (alpha-aminocarbonyl intermediate)
      formed from methylglyoxal to give 4- or 5-methylimidazole. The levels of 4(5)
      methylimidazole found in commercial cola soft drinks range from 0.30 MUg/mL
      (brand 3) to 0.36 MUg/mL (brands 1 and 5).

PMID- 21186781
TI  - The amyloid precursor protein C-terminal fragment C100 occurs in monomeric and
      dimeric stable conformations and binds gamma-secretase modulators.
AB  - The amyloid-beta (Abeta) peptide is contained within the C-terminal fragment
      (beta-CTF) of the amyloid precursor protein (APP) and is intimately linked to
      Alzheimer's disease. In vivo, Abeta is generated by sequential cleavage of beta
      CTF within the gamma-secretase module. To investigate gamma-secretase function,
      in vitro assays are in widespread use which require a recombinant beta-CTF
      substrate expressed in bacteria and purified from inclusion bodies, termed C100.
      So far, little is known about the conformation of C100 under different conditions
      of purification and refolding. Since C100 dimerization influences the efficiency
      and specificity of gamma-secretase cleavage, it is also of great interest to
      determine the secondary structure and the oligomeric state of the synthetic
      substrate as well as the binding properties of small molecules named gamma
      secretase modulators (GSMs) which we could previously show to modulate APP
      transmembrane sequence interactions [Richter et al. (2010) Proc. Natl. Acad. Sci.
      U.S.A. 107, 14597-14602]. Here, we use circular dichroism and continuous-wave
      electron spin resonance measurements to show that C100 purified in a buffer
      containing SDS at micelle-forming concentrations adopts a highly stable alpha
      helical conformation, in which it shows little tendency to aggregate or to form
      higher oligomers than dimers. By surface plasmon resonance analysis and molecular
      modeling we show that the GSM sulindac sulfide binds to C100 and has a preference
      for C100 dimers.

PMID- 21186782
TI  - Enhanced thermoelectric figure of merit of p-type half-Heuslers.
AB  - Half-Heuslers would be important thermoelectric materials due to their high
      temperature stability and abundance if their dimensionless thermoelectric figure
      of merit (ZT) could be made high enough. The highest peak ZT of a p-type half
      Heusler has been so far reported about 0.5 due to the high thermal conductivity.
      Through a nanocomposite approach using ball milling and hot pressing, we have
      achieved a peak ZT of 0.8 at 700  degrees C, which is about 60% higher than the
      best reported 0.5 and might be good enough for consideration for waste heat
      recovery in car exhaust systems. The improvement comes from a simultaneous
      increase in Seebeck coefficient and a significant decrease in thermal
      conductivity due to nanostructures. The samples were made by first forming
      alloyed ingots using arc melting and then creating nanopowders by ball milling
      the ingots and finally obtaining dense bulk by hot pressing. Further improvement
      in ZT is expected when average grain sizes are made smaller than 100 nm.

PMID- 21186786
TI  - Disorder and segregation in B-C-N graphene-type layers and nanotubes: tuning the
      band gap.
AB  - We investigate structural and electronic properties of B-C-N (boron-carbon
      nitrogen) layers and nanotubes considering the positional disorder of the B, C,
      and N atoms, using a combination of first principles and simulated annealing
      calculations. During the annealing process, we find that the atoms segregate into
      isolated, irregularly shaped graphene islands immersed in BN. We also find that
      the formation of the carbon islands strongly affects the electronic properties of
      the materials. For instance, in the case of layers and nanotubes with the same
      number of B and N atoms, we find that the band gap increases during the simulated
      annealing. This indicates that, for a given stoichiometry, the electronic and
      optical properties of B-C-N layers and nanotubes can be tuned by growth kinetics.
      We also find that the excess of B or N atoms results in large variations in the
      band gap and work function.

PMID- 21186787
TI  - 1,3,5-Trisubstituted and 5-acyl-1,3-disubstituted hydantoin derivatives via novel
      sequential three-component reaction.
AB  - 1,2-Diaza-1,3-dienes (DDs) react as Michael acceptors with primary amines to
      afford alpha-aminohydrazone derivatives that were in situ coupled with
      isocyanates. Intramolecular ring closure of the asymmetric urea derivatives so
      formed allows for a selectively substituted hydantoin ring to be obtained. The
      hydrazone side chain introduced by the conjugated heterodiene system at the 5
      position of the heterocycle represents a valuable functionality for accessing
      novel 5-acyl derivatives difficult to obtain by other methods.

PMID- 21186788
TI  - Titanium-catalyzed stereoselective synthesis of spirooxindole oxazolines.
AB  - A regio- and stereoselective cyclization between isatins and 5-methoxyoxazoles
      has been developed using catalytic titanium(IV) chloride (10 or 20 mol %) to
      afford spiro[3,3'-oxindoleoxazolines] in excellent yield (up to 99%) and
      diastereoselectivity (dr >99:1). Substitution at the 4-position of the oxazole
      controls nucleophilic attack to provide either the 2-oxazoline or 3-oxazoline
      spirocycle with excellent (>99:1) regiocontrol.

PMID- 21186789
TI  - Asymmetric synthesis of axially chiral biaryl diphosphine ligands by rhodium
      catalyzed enantioselective intramolecular double [2 + 2 + 2] cycloaddition.
AB  - The concise synthesis of axially chiral biaryl diphosphine ligands by the rhodium
      catalyzed intramolecular [2 + 2 + 2] cycloaddition of hexayne diphosphine oxides
      has been achieved. These new chiral diphosphine ligands could be employed as a
      ligand for the rhodium-catalyzed asymmetric catalyses.

PMID- 21186790
TI  - Quantification of the hygroscopic effect of soot aging in the atmosphere:
      laboratory simulations.
AB  - We use a laboratory approach for the quantification of the water uptake by
      particles with varying amounts of sulfates to simulate the aging of fossil fuel
      combustion particles in the atmosphere. Diesel fuel and aviation kerosene
      laboratory-made soots are chosen as representative of the hydrophobic fraction of
      diesel and aircraft engine-emitted particulates and commercial carbon blacks are
      used as surrogates for industry emissions. The transformation of soot hydration
      properties from hydrophobic, through hydrophilic, to hygroscopic is demonstrated
      based on the amount of water uptake by the laboratory-produced EC soot covered by
      sulfates as the amount of sulfate increases. The mechanism of water/soot
      interaction changes from an adsorption on active sites to a water film formation
      and to the dissolution of water into the water-soluble sulfate, while the amount
      of sulfate increases. Laboratory simulations show that coverage of EC soot by
      organics diminishes the effect of sulfuric acid deposition. We demonstrate that
      the surface chemical properties and the size of primary particles affect the
      amount of water taken up by the soot particles and their aging in the atmosphere.

PMID- 21186791
TI  - Coomassie staining as loading control in Western blot analysis.
AB  - In Western blotting, immunodetection of housekeeping proteins is routinely
      performed to detect differences in electrophoresis loading. The present work
      describes a much faster and simpler protein staining method, which is compatible
      with ordinary blocking conditions. In addition, the method can be used after
      immunodetection with superior linearity compared to ordinary staining methods.
      After immunoblotting and staining, protein bands can be further identified using
      peptide mass fingerprinting.

PMID- 21186792
TI  - Small interfering RNA knocks down the molecular target of alendronate, farnesyl
      pyrophosphate synthase, in osteoclast and osteoblast cultures.
AB  - Farnesyl pyrophosphate synthase (FPPS), an enzyme in the mevalonate pathway, is
      the inhibition target of alendronate, a potent FDA-approved nitrogen-containing
      bisphosphonate (N-BP) drug, at the molecular level. Alendronate not only inhibits
      osteoclasts but also has been reported to positively affect osteoblasts. This
      study assesses the knockdown effects of siRNA targeting FPPS compared with
      alendronate in both osteoclast and osteoblast cultures. Primary murine bone
      marrow cell-induced osteoclasts and the preosteoblast MC3T3-E1 cell line were
      used to assess effects of anti-FPPS siRNA compared with alendronate. Results show
      that both FPPS mRNA message and protein knockdown in serum-based culture is
      correlated with reduced osteoclast viability. FPPS siRNA is more potent than 10
      MUM alendronate, but less potent than 50 MUM alendronate on reducing osteoclast
      viability. Despite FPPS knockdown, no significant changes were observed in
      osteoblast proliferation. FPPS knockdown promotes osteoblast differentiation
      significantly but not cell mineral deposition. However, compared with 50 MUM
      alendronate dosing, FPPS siRNA does not exhibit cytotoxic effects on osteoblasts
      while producing significant effects on ostoblast differentiation. Both siRNA and
      alendronate at tested concentrations do not have significant effects on cultured
      osteoblast mineralization. Overall, results indicate that siRNA against FPPS
      could be useful for selectively inhibiting osteoclast-mediated bone resorption
      and improving bone mass maintenance by influencing both osteoclasts and
      osteoblasts in distinct ways.

PMID- 21186793
TI  - Structure-based design of potent and selective 2-(quinazolin-2-yl)phenol
      inhibitors of checkpoint kinase 2.
AB  - Structure-based design was applied to the optimization of a series of 2
      (quinazolin-2-yl)phenols to generate potent and selective ATP-competitive
      inhibitors of the DNA damage response signaling enzyme checkpoint kinase 2
      (CHK2). Structure-activity relationships for multiple substituent positions were
      optimized separately and in combination leading to the 2-(quinazolin-2-yl)phenol
      46 (IC(50) 3 nM) with good selectivity for CHK2 against CHK1 and a wider panel of
      kinases and with promising in vitro ADMET properties. Off-target activity at hERG
      ion channels shown by the core scaffold was successfully reduced by the addition
      of peripheral polar substitution. In addition to showing mechanistic inhibition
      of CHK2 in HT29 human colon cancer cells, a concentration dependent
      radioprotective effect in mouse thymocytes was demonstrated for the potent
      inhibitor 46 (CCT241533).

PMID- 21186795
TI  - Pyrimidine derivatives as potent and selective A3 adenosine receptor antagonists.
AB  - Two regioisomeric series of diaryl 2- or 4-amidopyrimidines have been synthesized
      and their adenosine receptor affinities were determined in radioligand binding
      assays at the four human adenosine receptors (hARs). Some of the ligands prepared
      herein exhibit remarkable affinities (K(i) < 10 nm) and, most noticeably, the
      absence of activity at the A(1), A(2A), and A(2B) receptors. The structural
      determinants that support the affinity and selectivity profiles of the series
      were highlighted through an integrated computational approach, combining a 3D
      QSAR model built on the second generation of GRid INdependent Descriptors
      (GRIND2) with a novel homology model of the hA(3) receptor. The robustness of the
      computational model was subsequently evaluated by the design of new derivatives
      exploring the alkyl substituent of the exocyclic amide group. The synthesis and
      evaluation of the novel compounds validated the predictive power of the model,
      exhibiting excellent agreement between predicted and experimental activities.

PMID- 21186794
TI  - alpha,beta-Unsaturated carbonyl system of chalcone-based derivatives is
      responsible for broad inhibition of proteasomal activity and preferential killing
      of human papilloma virus (HPV) positive cervical cancer cells.
AB  - Proteasome inhibitors have potential for the treatment of cervical cancer. We
      describe the synthesis and biological characterization of a new series of 1,3
      diphenylpropen-1-one (chalcone) based derivatives lacking the boronic acid
      moieties of the previously reported chalcone-based proteasome inhibitor 3,5-bis(4
      boronic acid benzylidene)-1-methylpiperidin-4-one and bearing a variety of amino
      acid substitutions on the amino group of the 4-piperidone. Our lead compound 2
      (RA-1) inhibits proteasomal activity and has improved dose-dependent
      antiproliferative and proapoptotic properties in cervical cancer cells containing
      human papillomavirus. Further, it induces synergistic killing of cervical cancer
      cell lines when tested in combination with an FDA approved proteasome inhibitor.
      Exploration of the potential mechanism of proteasomal inhibition by our lead
      compound using in silico docking studies suggests that the carbonyl group of its
      oxopiperidine moiety is susceptible to nucleophilic attack by the gamma
      hydroxythreonine side chain within the catalytic sites of the proteasome.

PMID- 21186796
TI  - Design and synthesis of pyrimidinone and pyrimidinedione inhibitors of dipeptidyl
      peptidase IV.
AB  - The discovery of two classes of heterocyclic dipeptidyl peptidase IV (DPP-4)
      inhibitors, pyrimidinones and pyrimidinediones, is described. After a single oral
      dose, these potent, selective, and noncovalent inhibitors provide sustained
      reduction of plasma DPP-4 activity and lowering of blood glucose in animal models
      of diabetes. Compounds 13a, 27b, and 27j were selected for development.

PMID- 21186797
TI  - Molecular trapping on two-dimensional binary supramolecular networks.
AB  - Molecular preferential adsorption on molecular patterned surfaces via specific
      intermolecular interactions provides an efficient route to construct ordered
      organic nanostructures for future nanodevices. Here, we demonstrate the
      preferential trapping of second-layer molecules atop two-dimensional binary
      supramolecular networks, F(16)CuPc on DIP:F(16)CuPc and 6P:F(16)CuPc systems,
      respectively, through intermolecular pi-pi interactions. The formation of the
      second-layer supramolecular nanostructures, individual molecular dots or linear
      molecular chains, can be controlled by the underlying molecular networks.

PMID- 21186798
TI  - Doping Cu in semiconductor nanocrystals: some old and some new physical insights.
AB  - Cu-doped inorganic semiconductors with concomitant optical properties have
      garnered enormous research interest in the last two decades. However,
      uncertainties over the origin of Cu emission, its oxidation state, resemblance
      with trap state emission, position of Cu d-state, emission spectral width, and
      moreover understanding of the doping mechanism restricted the wide development of
      the synthetic methodology for high-quality Cu-doped nanocrystals. It has been
      shown recently that the emission from Cu-doped semiconductor nanocrystals can
      span over a wide spectral window and could be a potential color tunable dispersed
      nanocrystal emitter. Herein, we report the size and composition of variable Cu
      doped ZnS/Zn(1-x)Cd(x)S zinc-blende (ZB) surface alloyed nanocrystals with
      intense, stable, and tunable emission covering the blue to red end of the visible
      spectrum. Further, the Cu dopant emission is distinguished from trap state
      emission, and the composition variable spectral broadening has been justified on
      the account of a different environment around the Cu ions in the host lattice.
      Whereas some findings are in agreement with past reports, several new physical
      insights presented here would help the community for an in-depth mechanistic
      study on Cu doping. Moreover, these doped nanocrystal emitters can be a promising
      candidate for application ranging from optoelectronics to bio-labeling.

PMID- 21186799
TI  - Dynamics of lysine side-chain amino groups in a protein studied by heteronuclear
      1H-15N NMR spectroscopy.
AB  - Despite their importance in macromolecular interactions and functions, the
      dynamics of lysine side-chain amino groups in proteins are not well understood.
      In this study, we have developed the methodology for the investigations of the
      dynamics of lysine NH3(+) groups by NMR spectroscopy and computation. By using 1H
      15N heteronuclear correlation experiments optimized for 15NH3(+) moieties, we
      have analyzed the dynamic behavior of individual lysine NH3(+) groups in human
      ubiquitin at 2  degrees C and pH 5. We modified the theoretical framework
      developed previously for CH3 groups and used it to analyze 15N relaxation data
      for the NH3(+) groups. For six lysine NH3(+) groups out of seven in ubiquitin, we
      have determined model-free order parameters, correlation times for bond rotation,
      and reorientation of the symmetry axis occurring on a pico- to nanosecond time
      scale. From CPMG relaxation dispersion experiment for lysine NH3(+) groups,
      slower dynamics occurring on a millisecond time scale have also been detected for
      Lys27. The NH3(+) groups of Lys48, which plays a key role as the linkage site in
      ubiquitination for proteasomal degradation, was found to be highly mobile with
      the lowest order parameter among the six NH3(+) groups analyzed by NMR. We
      compared the experimental order parameters for the lysine NH3(+) groups with
      those from a 1 MUs molecular dynamics simulation in explicit solvent and found
      good agreement between the two. Furthermore, both the computer simulation and the
      experimental correlation times for the bond rotations of NH3(+) groups suggest
      that their hydrogen bonding is highly dynamic with a subnanosecond lifetime. This
      study demonstrates the utility of combining NMR experiment and simulation for an
      in-depth characterization of the dynamics of these functionally most important
      side-chains of ubiquitin.

PMID- 21186800
TI  - Preferential interaction coefficients of proteins in aqueous arginine solutions
      and their molecular origins.
AB  - Preferential interaction coefficients provide a thermodynamic measure to quantify
      the interactions between cosolutes and a protein. Preferential interactions of
      cosolutes can be measured experimentally using dialysis/densimetry and vapor
      pressure osmometry (VPO) techniques. The cosolute arginine is a widely used
      aggregation suppressor with a seemingly unique behavior. Its role in protein
      aggregation has been studied extensively, although a complete mechanistic
      understanding of its behavior is lacking. Moreover, due to experimental
      limitations, experimental preferential interaction data for arginine has only
      been reported at low concentrations. Schneider and Trout ( J. Phys. Chem. B 2009
      , 113 , 7 ) have reported experimental preferential interaction data for argHCl
      (up to 0.7 m), and their study raised several interesting questions about the
      preferential interaction of arginine with proteins. Arginine is attracted to
      proteins at low concentrations but it was highly excluded at high concentrations.
      Furthermore, the preferential interaction coefficient values were found to vary
      as a square of the concentration, which is different from commonly observed
      linear relationship for other cosolutes like urea, glycerol, guanidinium
      hydrochloride, etc. In this study, preferential interaction coefficients of
      argHCl have been estimated computationally for two proteins (lysozyme and alpha
      chymotripsinogen A) for a large concentration range (up to 2.8 m). On the basis
      of these results, the molecular level interactions responsible for the nonlinear
      exclusion of arginine from the protein surface are identified.

PMID- 21186801
TI  - Effects of G33A and G33I mutations on the structures of monomer and dimer of the
      amyloid-beta fragment 29-42 by replica exchange molecular dynamics simulations.
AB  - The early formed oligomers of amyloid-beta proteins with 40 and 42 amino acids
      are believed to be the culprits of Alzheimer's disease. Abeta1-42 peptides with
      alanine and isoleucine mutations of glycine 33 are known to be much less toxic
      than the wild-type Abeta1-42 and promote the aggregation process in vitro. The
      fragment Abeta29-42 has also been shown to form fibrils, disrupt Abeta1-42
      oligomerization, and inhibit Abeta1-42-induced neurotoxicity. As a first step
      toward understanding the impact of G33A and G33I mutations on the earliest steps
      along the Abeta1-42 aggregation pathway, we have studied the structures of the
      monomer and dimer of Abeta29-42 and its two G33 variants using coarse-grained
      replica exchange molecular dynamics simulations. These simulations, totaling 15
      MUs, indicate that both substitutions impact the conformational ensemble of
      Abeta29-42. For the monomer, the population of the beta-hairpin is high for wild
      type Abeta29-42, but marginal for Abeta29-42 G33I mutant. The three dimers are
      also stabilized by different patterns of interaction. The data are discussed in
      terms of the differences in the aggregation characteristics between wild-type
      Abeta1-42 and its two G33A and G33I variants.

PMID- 21186802
TI  - Screening the optical properties of Ag-Au alloy gradients formed by bipolar
      electrodeposition using surface enhanced Raman spectroscopy.
AB  - We report the synthesis of Ag-Au alloy gradients on stainless steel substrates
      using bipolar electrodeposition (BP-ED), a technique based on the existence of a
      potential gradient at the interface of a bipolar electrode (BPE) and an
      electrolytic solution. The interfacial potential gradient causes the rates of
      electrodeposition of Ag and Au to vary along the length of the BPE, leading to
      the electrodeposition of a chemical concentration gradient. The surface
      morphology of the electrodeposits was characterized using scanning electron
      microscopy (SEM), and their chemical composition was determined using energy
      dispersive X-ray spectroscopy (EDX). Self-assembled monolayers of a Raman-active
      probe molecule (benzene thiol) were allowed to form on the surface of the alloy
      gradients, and confocal Raman microscopy was employed to determine the alloy
      composition that resulted in the maximum surface enhanced Raman scattering (SERS)
      intensity. An alloy composition of ca. 70% Ag/30% Au was found to be optimum for
      SERS excited using 514.5 nm radiation, and it is explained on the basis of
      composition-dependent changes in the local surface plasmon resonance (LSPR) of
      the electrodeposited Ag-Au alloy.

PMID- 21186803
TI  - HIV protease-mediated activation of sterically capped proteasome inhibitors and
      substrates.
AB  - Strategies for selectively killing HIV-infected cells present an appealing
      alternative to traditional antiretroviral drugs. We show here the first example
      of an inactive "Trojan horse" molecule that releases a cytotoxic, small-molecule
      proteasome inhibitor upon cleavage by HIV-1 protease. As a proof-of-concept
      strategy, the protein avidin was used to block entry of the compound into the
      proteasome in the absence of HIV-1 protease. We demonstrate that this strategy is
      also feasible without requiring an exogenous protein; a polylysine dendrimer
      containing molecule is unable to enter the proteasome until cleaved by HIV-1
      protease. These results demonstrate that conditional proteasome inhibitors could
      prove useful in the development of new tools for chemical biology and future
      therapeutics.

PMID- 21186804
TI  - Vibrational circular dichroism as a probe of fibrillogenesis: the origin of the
      anomalous intensity enhancement of amyloid-like fibrils.
AB  - Amyloid fibrils are affiliated with various human pathologies. Knowledge of their
      molecular architecture is necessary for a detailed understanding of the mechanism
      of fibril formation. Vibrational circular dichroism (VCD) spectroscopy has
      recently shown sensitivity to amyloid fibrils [Ma et al. J. Am. Chem. Soc. 2007,
      129, 12364 and Measey et al. J. Am. Chem. Soc. 2009, 131, 18218]. In particular,
      amyloid fibrils give rise to an intensity enhanced signal in the amide I band
      region of the corresponding VCD spectrum, offering promise of utilizing such a
      method for probing fibrillogenesis and the chiral structure of fibrils. Herein,
      we further investigate this phenomenon and demonstrate the use of VCD to probe
      the fibril formation kinetics of a short alanine-rich peptide. To elucidate the
      origin of the anomalous VCD intensity enhancement, we use an excitonic coupling
      model to simulate the VCD spectrum of stacked beta-sheets containing one (Ising
      like model) and two amide I oscillators per strand, as models for the underlying
      amyloid-fibril secondary structure. With this simple model, we show that the VCD
      intensity enhancement of amyloid-like fibrils results from intrasheet and, to a
      more limited extent, also from intersheet vibrational coupling between stacked
      beta-sheets. The enhancement requires helically twisted sheets and is most
      pronounced for arrangements with parallel-oriented strands. Both the intersheet
      distance and the orientation of the amide I transition dipole moments of
      neighboring sheets are found to modulate the intensity enhancement of the amide I
      VCD signal. Moreover, our simulations suggest that, depending on the three
      dimensional arrangement of the beta-strands, the sign of the VCD signal of
      amyloid-like fibrils can be used to distinguish between right- and left-handed
      helical twists of parallel-oriented beta-sheets. We compare the results of our
      simulation to experimental spectra of two short peptides, GNNQQNY, the N-terminal
      peptide fragment of the yeast prion protein Sup35, and an amyloidogenic alanine
      rich peptide, AKY8. Our results demonstrate the advantages of using VCD
      spectroscopy to probe the kinetics of peptide and protein aggregation as well as
      the chirality of the resulting supramolecular structure.

PMID- 21186805
TI  - Characterization of tiacumicin B biosynthetic gene cluster affording diversified
      tiacumicin analogues and revealing a tailoring dihalogenase.
AB  - The RNA polymerase inhibitor tiacumicin B is currently undergoing phase III
      clinical trial for treatment of Clostridium difficile associated diarrhea with
      great promise. To understand the biosynthetic logic and to lay a foundation for
      generating structural analogues via pathway engineering, the tiacumicin B
      biosynthetic gene cluster was identified and characterized from the producer
      Dactylosporangium aurantiacum subsp. hamdenensis NRRL 18085. Sequence analysis of
      a 110,633 bp DNA region revealed the presence of 50 open reading frames (orfs).
      Functional investigations of 11 orfs by in vivo inactivation experiments,
      preliminarily outlined the boundaries of the tia-gene cluster and suggested that
      31 orfs were putatively involved in tiacumicin B biosynthesis. Functions of a
      halogenase (TiaM), two glycosyltransferases (TiaG1 and TiaG2), a sugar C
      methyltransferase (TiaS2), an acyltransferase (TiaS6), and two cytochrome P450s
      (TiaP1 and TiaP2) were elucidated by isolation and structural characterization of
      the metabolites from the corresponding gene-inactivation mutants. Accumulation of
      18 tiacumicin B analogues from 7 mutants not only provided experimental evidence
      to confirm the proposed functions of individual biosynthetic enzymes, but also
      set an example of accessing microbial natural product diversity via genetic
      approach. More importantly, biochemical characterization of the FAD-dependent
      halogenase TiaM reveals a sequentially acting dihalogenation step tailoring
      tiacumicin B biosynthesis.

PMID- 21186806
TI  - Analysis of the complex formation of heparin with protamine by light scattering
      and analytical ultracentrifugation: implications for blood coagulation
      management.
AB  - Heparin, a linear glycosaminoglycan, is used in different forms in
      anticoagulation treatment. Protamine, a highly positive charged peptide
      containing about 32 amino acids, acts as an antagonist for heparin to restore
      normal blood coagulation. The complex formation of protamine with heparin was
      analyzed by a combination of analytical ultracentrifugation and light scattering.
      Titration of heparin with protamine in blood plasma preparations results in a
      drastic increase of turbidity, indicating the formation of nanoscale particles. A
      similar increase of turbidity was observed in physiological saline solution with
      or without human serum albumin (HSA). Particle size analysis by analytical
      ultracentrifugation revealed a particle radius of approximately 30 nm for
      unfractionated heparin and of approximately 60 nm for low molecular weight
      heparin upon complexation with excess protamine, in agreement with atomic force
      microscopy data. In the absence of HSA, larger and more heterogeneous particles
      were observed. The particles obtained were found to be stable for hours. The
      particle formation kinetics was analyzed by light scattering at different
      scattering angles and was found to be complete within several minutes. The time
      course of particle formation suggests a condensation reaction, with sigmoidal
      traces for low heparin concentrations and quasi-first-order reaction for high
      heparin concentrations. Under all conditions, the final scattering intensity
      reached after several minutes was found to be proportional to the amount of
      heparin in the blood plasma or buffer solution, provided that excess protamine
      was available and no multiple scattering occurred. On the basis of a direct
      relation between particle concentration and the heparin concentration present
      before protaminization, a light scattering assay was developed which permits the
      quantitative analysis of the heparin concentration in blood plasma and which
      could complement or even replace the activated clotting time test, which is
      currently the most commonly used method for blood coagulation management.

PMID- 21186808
TI  - Hydrosilylation with biscarbene Rh(I) complexes: experimental evidence for a
      silylene-based mechanism.
AB  - A detailed study investigating the mechanism of the hydrosilylation of 4-F
      acetophenone by N-heterocyclic biscarbene rhodium(I) complexes was performed,
      delivering substantial experimental evidence for a recently proposed catalytic
      cycle and explaining the observed side-product formation. Labeling experiments,
      silylene trapping reactions, and specific catalytic reactions were employed to
      substantiate each step of the catalytic cycle and explain the differences
      observed for different types of chiral catalysts. It is further shown that
      hydrosilylation and dehydrocoupling reactions with dihydrosilanes are
      mechanistically related.

PMID- 21186809
TI  - Poly(o-phenylenediamine) colloid-quenched fluorescent oligonucleotide as a probe
      for fluorescence-enhanced nucleic acid detection.
AB  - In this Letter, we demonstrate that chemical oxidation polymerization of o
      phenylenediamine (OPD) by potassium bichromate at room temperature results in the
      formation of submicrometer-scale poly(o-phenylenediamine) (POPD) colloids. Such
      colloids can absorb and quench dye-labeled single-stranded DNA (ssDNA) very
      effectively. In the presence of a target, a hybridization event occurs, which
      produces a double-stranded DNA (dsDNA) that detaches from the POPD surface,
      leading to recovery of dye fluorescence. With the use of an oligonucleotide (OND)
      sequence associated with human immunodeficiency virus (HIV) as a model system, we
      demonstrate the proof of concept that POPD colloid-quenched fluorescent OND can
      be used as a probe for fluorescence-enhanced nucleic acid detection with
      selectivity down to single-base mismatch.

PMID- 21186810
TI  - Theoretical and computational analysis of static and dynamic anomalies in water
      DMSO binary mixture at low DMSO concentrations.
AB  - Experiments have repeatedly observed both thermodynamic and dynamic anomalies in
      aqueous binary mixtures, surprisingly at low solute concentration. Examples of
      such binary mixtures include water-DMSO, water-ethanol, water-tertiary butyl
      alcohol (TBA), and water-dioxane, to name a few. The anomalies have often been
      attributed to the onset of a structural transition, whose nature, however, has
      been left rather unclear. Here we study the origin of such anomalies using large
      scale computer simulations and theoretical analysis in water-DMSO binary mixture.
      At very low DMSO concentration (below 10%), small aggregates of DMSO are solvated
      by water through the formation of DMSO-(H(2)O)(2) moieties. As the concentration
      is increased beyond 10-12% of DMSO, spanning clusters comprising the same
      moieties appear in the system. Those clusters are formed and stabilized not only
      through H-bonding but also through the association of CH(3) groups of DMSO. We
      attribute the experimentally observed anomalies to a continuum percolation-like
      transition at DMSO concentration X(DMSO) ~ 12-15%. The largest cluster size of
      CH(3)-CH(3) aggregation clearly indicates the formation of such percolating
      clusters. As a result, a significant slowing down is observed in the decay of
      associated rotational auto time correlation functions (of the S?O bond vector of
      DMSO and O-H bond vector of water). Markedly unusual behavior in the mean square
      fluctuation of total dipole moment again suggests a structural transition around
      the same concentration range. Furthermore, we map our findings to an interacting
      lattice model which substantiates the continuum percolation model as the reason
      for low concentration anomalies in binary mixtures where the solutes involved
      have both hydrophilic and hydrophobic moieties.

PMID- 21186811
TI  - Biomass-based composites from poly(lactic acid) and wood flour by vapor-phase
      assisted surface polymerization.
AB  - To prepare biomass-based composites in an environmentally benign manner, vapor
      phase assisted surface polymerization (VASP) was applied to prepare the
      composites from wood flour and poly(l-lactic acid) (PLLA) without solvent. VASP
      of l,l-lactide successfully proceeded on the wood flour surfaces, resulting in
      surface coverage by newly generated PLLA. For obtained PLLA/wood flour
      composites, it was clarified that grafting of PLLA on wood flour surfaces had
      occurred to form covalently bonded composites, with the accumulated PLLA layers
      having crystallized in situ during VASP. Resulting PLLA layers showed very high
      crystallinity of 79.2% and a high melting point close to the equilibrium melting
      point. Moreover, thermal degradation behavior of the composites suggested a
      cooperative degradation manner of the components.

PMID- 21186812
TI  - Electron beam irradiation-enhanced wettability of carbon fibers.
AB  - A simple but controllable way of altering the surface nature of carbon fibers,
      without sacrificing their intrinsic mechanical properties, is demonstrated using
      electron beam irradiation. Such treatment leads to physically improved roughness
      as well as chemically introduced hydrophilic oxygen-containing functional groups
      on the surface of carbon fibers that are essential for assuring an efficient
      stress transfer from carbon fibers to a polymer matrix.

PMID- 21186813
TI  - Estimation of standard reduction potentials of halogen atoms and alkyl halides.
AB  - Standard reduction potentials, SRPs, of the halogen atoms have been calculated in
      water on the basis of an appropriate thermochemical cycle. Using the best up-to
      date thermodynamic data available in the literature, we have calculated E(o)(X*/X
      ) values of 3.66, 2.59, 2.04, and 1.37 V vs SHE for F*, Cl*, Br*, and I*,
      respectively. Additionally, we have computed the SRPs of Cl*, Br*, and I* in
      acetonitrile (CH3CN) and dimethylformamide (DMF) by correcting the values
      obtained in water for the free energies of transfer of X* and X- from water to
      the nonaqueous solvent S and the intersolvent potential between water and S. From
      the values of E(o)(X */X-) in CH(3)CN and DMF, the SRPs of a series of alkyl
      halides of relevance to atom transfer radical polymerization and other important
      processes such as pollution abatement have been calculated in these two solvents.
      This has been done with the aid of a thermochemical cycle involving the gas-phase
      homolytic dissociation of the C-X bond, solvation of RX, R*, and X*, and
      reduction of X* to X- in solution.

PMID- 21186814
TI  - Real-time methods for estimating organic component mass concentrations from
      aerosol mass spectrometer data.
AB  - We use results from positive matrix factorization (PMF) analysis of 15 urban
      aerosol mass spectrometer (AMS) data sets to derive simple methods for estimating
      major organic aerosol (OA) component concentrations in real time. PMF analysis
      extracts mass spectral (MS) profiles and mass concentrations for key OA
      components such as hydrocarbon-like OA (HOA), oxygenated OA (OOA), low-volatility
      OOA (LV-OOA), semivolatile OOA (SV-OOA), and biomass burning OA (BBOA). The
      variability in the component MS across all sites is characterized and used to
      derive standard profiles for real-time estimation of component concentrations.
      Two methods for obtaining first-order estimates of the HOA and OOA mass
      concentrations are evaluated. The first approach is the tracer m/z method, in
      which the HOA and OOA concentrations are estimated from m/z 57 and m/z 44 as
      follows: HOA ~ 13.4 * (C(57) - 0.1 * C(44)) and OOA ~ 6.6 * C(44), where C(i) is
      the equivalent mass concentration of tracer ion m/z i. The second approach uses a
      chemical mass balance (CMB) method in which standard HOA and OOA profiles are
      used as a priori information for calculating their mass concentrations. The HOA
      and OOA mass concentrations obtained from the first-order estimates are evaluated
      by comparing with the corresponding PMF results for each site. Both methods
      reproduce the HOA and OOA concentrations to within ~30% of the results from
      detailed PMF analysis at most sites, with the CMB method being slightly better.
      For hybrid CMB methods, we find that fixing the LV-OOA spectrum and not
      constraining the other spectra produces the best results.

PMID- 21186815
TI  - Cross-linked bacterial cellulose networks using glyoxalization.
AB  - In this study, we demonstrate that bacterial cellulose (BC) networks can be cross
      linked via glyoxalization. The fracture surfaces of samples show that, in the dry
      state, less delamination occurs for glyoxalized BC networks compared to
      unmodified BC networks, suggesting that covalent bond coupling between BC layers
      occurs during the glyoxalization process. Young's moduli of dry unmodified BC
      networks do not change significantly after glyoxalization. The stress and strain
      at failure are, however, reduced after glyoxalization. However, the wet
      mechanical properties of the BC networks are improved by glyoxalization. Raman
      spectroscopy is used to demonstrate that the stress-transfer efficiency of
      deformed dry and wet glyoxalized BC networks is significantly increased compared
      to unmodified material. This enhanced stress-transfer within the networks is
      shown to be a consequence of the covalent coupling induced during glyoxalization
      and offers a facile route for enhancing the mechanical properties of BC networks
      for a variety of applications.

PMID- 21186816
TI  - Dynamic characteristic of amitriptyline in water by ultrasonic relaxation method
      and molecular orbital calculation.
AB  - Ultrasonic absorption coefficients in the frequency range of 0.8-220 MHz have
      been measured in aqueous solution of amitriptyline (3-(10,11-dihydro-5H
      dibenzo[a,d]cycloheptene-5-ylidene)-N,N-dimethyl-1-propanamine) in the
      concentration range from 0.20 to 0.60 mol dm(-3) at 25  degrees C. A single
      relaxational phenomenon has been observed, and the relaxation frequency is
      independent of the concentration. It has been also observed that the amplitude of
      the relaxational absorption increases linearly with the analytical concentration.
      From these ultrasonic relaxation data, it has been concluded that the relaxation
      is associated with a unimolecular reaction due to a conformational change of the
      solute molecule, such as a structural change due to a rotational motion of a
      group in the solute molecule. Molecular orbital semiempirical methods using AM1
      (Austin model 1) and PM3 (modified neglect of diatomic overlap parametric method
      3) have been applied to obtain the standard enthalpy of formation for
      amitriptyline molecule at various dihedral angles around one of the bonds in
      alkylamine side chain. The results have shown the two clear minimum standard
      enthalpies of formation for amitriptyline. From the difference of the two values,
      the standard enthalpy change between the two stable conformers has been
      calculated be 2.9 kJ mol(-1). On a rough assumption that the standard enthalpy
      change reflects the standard free energy change, the equilibrium constant for the
      rotational isomers has been estimated to be 0.31. Combining this value with the
      experimental ultrasonic relaxation frequency, the backward and forward rate
      constants have been evaluated. The standard enthalpy change of the reaction has
      been also estimated from the concentration dependence of the maximum absorption
      per wavelength, and it has been close to that calculated by the semiempirical
      methods. The ultrasonic absorption measurements have been also carried out in
      amitriptyline solution in the presence of beta-cyclodextrin. However, the
      ultrasonic relaxation has not been found in the above frequency range. The result
      has been discussed in relation to the host-guest complex formation between beta
      cyclodextrin and amitriptyline.

PMID- 21186817
TI  - Effects of polyphenolic compounds on tumor necrosis factor-alpha (TNF-alpha)
      induced changes of adipokines and oxidative stress in 3T3-L1 adipocytes.
AB  - Over the last few decades, obesity has become a global epidemic in both developed
      and developing countries. Recent studies have indicated that obesity is closely
      associated with chronic inflammation characterized by abnormal levels of
      adipocytokines and inflammatory cytokines in adipocytes. The aim of this work was
      to study the effects of 21 polyphenolic compounds on tumor necrosis factor-alpha
      (TNF-alpha)-induced changes of adipokines and oxidative stress in 3T3-L1
      adipocytes. The results showed that p-coumaric acid, quercetin, and resveratrol
      have greater inhibition (p < 0.05) of a TNF-alpha-induced increase in the
      production of interleukin-6 (IL-6) among 21 tested polyphenolic compounds. p
      Coumaric acid, quercetin, and resveratrol demonstrated inhibitions of TNF-alpha
      induced changes in levels of monocyte chemoattractant protein-1 (MCP-1),
      plasminogen activator inhibitor-1 (PAI-1), and intracellular reactive oxygen
      species (ROS) in 3T3-L1 adipocytes. Furthermore, p-coumaric acid, quercetin, and
      resveratrol increased levels (p < 0.05) of secreted adiponectin, superoxide
      dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), and glutathione
      S-transferase (GST) in TNF-alpha-treated 3T3-L1 adipocytes. These results
      indicate that the inhibition of TNF-alpha-induced changes of adipokines and
      oxidative stress by some polyphenolic compounds might have further implications
      in preventing obesity-related pathologies.

PMID- 21186818
TI  - Characterization of the key aroma compounds in cooked grey mullet (Mugil
      cephalus) by application of aroma extract dilution analysis.
AB  - Aroma and aroma-active compounds of wild grey mullet ( Mugil cephalus ) were
      analyzed by gas chromatography-mass spectrometry-olfactometry (GC-MS-O).
      According to sensory analysis, the aromatic extract obtained by simultaneous
      distillation and extraction (SDE) was representative of grey mullet odor. A total
      of 50 aroma compounds were identified and quantified in grey mullet. Aldehydes
      were qualitatively and quantitatively the most dominant volatiles in grey mullet.
      Aroma extract dilution analysis (AEDA) was used for the determination of aroma
      active compounds of fish sample. A total of 29 aroma-active compounds were
      detected in aromatic extract of grey mullet, of which 24 were identified. On the
      basis of the flavor dilution (FD) factor, the most powerful aroma active
      compounds identified in the extract were (Z)-4-heptenal and nonanal, which were
      described as the strong cooked fish and green-fruity odor, respectively.

PMID- 21186819
TI  - Temperature-dependent in situ ligand cyclization via C?C coupling and formation
      of a spin-crossover iron(II) coordination polymer.
AB  - The reaction of N(1),N(2)-bis(pyridin-4-ylmethylene)ethane-1,2-diamine (L) with
      Fe(NCS)(2) under various temperatures gave rise to three iron(II) coordination
      polymers, namely, one-dimensional [Fe(L')(NCS)(2)] (1), two-dimensional
      [Fe(L)(2)(NCS)(2)].H(2)O (2), and one-dimensional
      [Fe(L)(2)(NCS)(2)].2CH(2)Cl(2).4MeOH (3). The formation of 1 involved an in situ
      C?C coupling reaction, L to L' [L' = 5,6-di(pyridin-4-yl)-1,2,3,4
      tetrahydropyrazine], which was catalyzed by cyanide ions decomposed from
      thiocyanates; the manganese(II) (1a) and zinc(II) (1b) analogues of 1 were also
      synthesized for comparison. Magnetic studies showed that complex 1 underwent a
      pressure-dependent one-step incomplete spin transition whereas complexes 2 and 3
      were paramagnetic in the whole temperature range.

PMID- 21186821
TI  - Slow magnetic relaxation in novel Dy4 and Dy8 compounds.
AB  - Two novel dysprosium(III) clusters have been prepared and structurally
      characterized. One has a tetranuclear core with a rare zigzag arrangement, and
      the other is an unprecedented octanuclear cluster with six triangular Dy(3) units
      sharing vertices. Both dysprosium(III) clusters possess frequency-dependent on
      alternating-current magnetic susceptibilities, indicating possible single
      molecule magnet behavior.

PMID- 21186820
TI  - Plasmonic focusing in symmetry broken nanocorrals.
AB  - Plasmonic focusing was investigated in symmetry broken nanocorrals under linearly
      polarized illumination. Near-field optical measurements of the perpendicular
      electric field show that a single subwavelength spot size of 320 nm can be
      generated. The interference pattern within the corral can be controlled by
      changing the polarization of optical excitation and the degree of symmetry
      breaking. The intensity enhancement factor was investigated using finite
      difference time-domain simulations and confirmed by analytical calculations
      taking into account the plasmon damping and multiple reflections against the
      corral wall.

PMID- 21186822
TI  - On the sensing mechanism in carbon nanotube chemiresistors.
AB  - There has been recent controversy whether the response seen in carbon nanotube
      (CNT) chemiresistors is associated with a change in the resistance of the
      individual nanotubes or changes in the resistance of the junctions. In this
      study, we carry out a network analysis to understand the relative contributions
      of the nanotubes and the junctions to the change in resistance of the nanotube
      network. We find that the dominant mode of detection in nanotube networks changes
      according to the conductance level (defect level) in the nanotubes. In networks
      with perfect nanotubes, changes in the junctions between adjacent nanotubes and
      junctions between the contacts and the CNTs can cause a detectable change in the
      resistance of the nanotube networks, while adsorption on the nanotubes has a
      smaller effect. In contrast, in networks with highly defective nanotubes, the
      changes in the resistance of the individual nanotubes cause a detectable change
      in the overall resistance of a chemiresistor network, while changes in the
      junctions have smaller effects. The combinational effect is also observed for the
      case in between. The results show that the sensing mechanism of a nanotube
      network can change according to the defect levels of the nanotubes, which may
      explain the apparently contradictory results in the literature.

PMID- 21186823
TI  - Protective effects of 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone to PC12
      cells against cytotoxicity induced by hydrogen peroxide.
AB  - Oxidative stress has been considered as a major cause of cellular injuries in
      various clinical abnormalities. One of the possible ways to prevent reactive
      oxygen species (ROS)-mediated cellular injury is dietary or pharmaceutical
      therapies to augment the endogenous antioxidant defense capacity. The present
      study found that 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), a
      chalcone isolated from the buds of Cleistocalyx operculatus, possessed
      cytoprotective activity in PC12 cells treated with H(2)O(2). The results showed
      that DMC could effectively increase cell viability [3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazoliumbromide (MTT) reduction], decrease the cell apoptotic
      percentage [annexin V/propidium iodide (AV/PI) assay], prevent the membrane from
      damage [lactate dehydrogenase (LDH) release], scavenge ROS formation, reduce
      caspase-3 activity, and attenuate the decrease of mitochondrial membrane
      potential (MMP) in PC12 cells treated with H(2)O(2). Meanwhile, DMC increased the
      catalytic activity of superoxide dismutase (SOD) and the cellular amount of
      glutathione (GSH), decreased the cellular amount of malondialdehyde (MDA), and
      decreased the production of lipid peroxidation in PC12 cells treated with
      H(2)O(2).

PMID- 21186824
TI  - Selective targeting of gold nanorods at the mitochondria of cancer cells:
      implications for cancer therapy.
AB  - We have observed that Au nanorods (NRs) have distinct effects on cell viability
      via killing cancer cells while posing negligible impact on normal cells and
      mesenchymal stem cells. Obvious differences in cellular uptake, intracellular
      trafficking, and susceptibility of lysosome to Au NRs by different types of cells
      resulted in selective accumulation of Au NRs in the mitochondria of cancer cells.
      Their long-term retention decreased mitochondrial membrane potential and
      increased reactive oxygen species level that enhances the likelihood of cell
      death. These findings thus provide guidance for the design of organelle-targeted
      nanomaterials in tumor therapy.

PMID- 21186825
TI  - Complex interplay and hierarchy of interactions in two-dimensional supramolecular
      assemblies.
AB  - In order to address the interplay of hydrogen bonding, dipolar interactions, and
      metal coordination, we have investigated the two-dimensional mono- and
      bicomponent self-assembly of three closely related diaminotriazine-based
      molecular building blocks and a complementary perylenetetracarboxylic diimide by
      means of scanning tunneling microscopy. The simplest molecular species, bis
      diaminotriazine-benzene, only interacts via hydrogen bonds and forms a unique
      supramolecular pattern on the Au(111) surface. For the two related molecular
      species, which exhibit in addition to hydrogen bonding also dipolar interactions
      and metal coordination, the number of distinct supramolecular structures
      increases dramatically with the number of possible interaction channels.
      Deposition together with the complementary perylene species, however, always
      results in a single well-defined supramolecular arrangement of molecules. A
      detailed analysis of the observed mono- and bicomponent assemblies allows
      shedding light on the hierarchy of the competing interactions, with important
      implications for the fabrication of surface-supported supramolecular networks by
      design.

PMID- 21186826
TI  - Formation and fate of bound residues from microbial biomass during 2,4-D
      degradation in soil.
AB  - During organic contaminant degradation in soil, bound or nonextractable residues
      (NER) are formed. Part of these residues may be biogenic, because degrading
      microorganisms assimilate carbon derived from the pollutant and mineralized CO(2)
      to form cellular components for example, [fatty acids (FA) and amino acids (AA)],
      which are subsequently stabilized within soil organic matter (SOM). We
      investigated the formation and fate of FA and AA from biodegradation of (13)C(6)
      2,4-D in soil and the incorporation of the (13)C-label into living biomass via
      (13)CO(2) fixation. After 64 days of incubation, (13)C-AA in SOM indicated that
      44% of the initially applied (13)C(6)-2,4-D equivalents had been converted to
      microbial biomass and finally to biogenic residues. The intermediate maximum of
      (13)C-FA in SOM indicated a 20% conversion of (13)C(6)-2,4-D to biomass, but
      (13)C-FA decreased to 50% of that value whereas (13)C-AA in the SOM remained
      stable. We provide the first evidence that nearly all bound residues from 2,4-D
      are biogenic, containing natural microbial residues stabilized in SOM. Because of
      biogenic residue formation, the potential risk of bound residues from readily
      metabolized xenobiotics in soils is highly overestimated. Hence, the formation of
      biogenic residues must be considered in general when performing mass balances of
      pollutant biodegradation in soils.

PMID- 21186827
TI  - Synthesis and immunogenicity of a glycopolymer conjugate.
AB  - A protective beta-mannan trisaccharide epitope from the Candida albicans cell
      wall phosphomannan has been synthesized and activated for copolymerization with
      acrylamide. The resulting glycopolymer displayed 33 trisaccharide haptens and was
      derivatized for conjugation to the immunogenic carrier protein, chicken serum
      albumin. The resulting conjugate achieves a high degree of oligosaccharide
      substitution while limiting the sites of substitution on the protein. The murine
      immune response against this conjugate was compared with the response to a
      trisaccharide-tetanus toxoid conjugate vaccine. The glycopolymer was shown to
      induce a more robust immune response with higher trisaccharide-specific antibody
      titers and with a significantly larger proportion of responding mice developing
      antibodies that bound the target, native cell wall antigen of C. albicans.

PMID- 21186828
TI  - Synthesis and reactivity of highly nucleophilic pyridines.
AB  - 3,4,5-Triamino-substituted pyridines are avid for electrophiles but are still
      willing to give them back. In these compounds three amino groups conjoin their
      forces into the heterocyclic nitrogen, making it a powerful Lewis base. A short
      and efficient synthesis is described, and the origin of its unique activity in
      nucleophilic organocatalysis is rationalized by kinetics and thermodynamic
      quantifications.

PMID- 21186829
TI  - Linking trehalose self-association with binary aqueous solution equation of
      state.
AB  - In aqueous solutions, trehalose possesses a high propensity to form hydrogen
      bonds with water as well as other trehalose molecules. This hydrogen bonding not
      only affects water structure but also promotes extensive concentration dependent
      aggregation of trehalose molecules, which may impact trehalose's role as a
      protective cosolute to biomacromolecules. To study the association of trehalose
      in aqueous solutions over a wide concentration range, we used molecular dynamics
      simulations based on two different force fields, as well as vapor pressure
      osmometry. By analyzing trehalose cluster size and fractal dimension in
      simulations, we estimate the cluster percolation threshold at 1.5-2.2 m.
      Experimentally, trehalose solutions showed positive deviations from ideal van't
      Hoff's law that grew with concentration. These variations in osmotic pressure can
      be explained using a simple equation of state that accounts for the repulsive
      excluded volume interactions between trehalose molecules as well as attractions
      reflected in sugar clustering. We find that simulations with both applied force
      fields result in reasonable representations of the solution equation of state.
      However, in contrast to experiments, the balance between the repulsive and
      attractive trehalose-trehalose interactions in simulations results in a slightly
      negative deviation from ideality, probably due to the moderately overaggregative
      nature of the force fields used.

PMID- 21186830
TI  - Nematic ordering of polymers in confined geometry applied to DNA packaging in
      viral capsids.
AB  - A density functional theory of the spatial distribution and biaxial nematic order
      of polymers of arbitrary length and rigidity inside a spherical cavity is
      proposed. The local order of different chain segments is considered as an
      alignment to a spatially varying director field of cylindrical symmetry. The
      steric interactions are taken into account in the second virial approximation.
      Polymer density and orientational order distributions inside the spherically
      cavity are the principal results. It was found that short and flexible polymers
      were located at the center of the sphere and were orientationaly disordered. Upon
      increasing polymer length and/or polymer rigidity, the location of the polymer
      was continuously shifted toward the surface of the spherical cavity and the
      polymer segments became gradually more aligned. Parameters have been selected to
      model the behavior of genomes in spherical viral capsids.

PMID- 21186831
TI  - Selection of Carbonic Anhydrase IX Inhibitors from One Million DNA-Encoded
      Compounds.
AB  - DNA-encoded chemical libraries, i.e., collections of compounds individually
      coupled to distinctive DNA fragments serving as amplifiable identification
      barcodes, represent a new tool for the de novo discovery of small molecule
      ligands to target proteins of pharmaceutical interest. Here, we describe the
      design and synthesis of a novel DNA-encoded chemical library containing one
      million small molecules. The library was synthesized by combinatorial assembly of
      three sets of chemical building blocks using Diels-Alder cycloadditions and by
      the stepwise build-up of the DNA barcodes. Model selections were performed to
      test library performance and to develop a statistical method for the analysis of
      high-throughput sequencing data. A library selection against carbonic anhydrase
      IX revealed a new class of submicromolar bis(sulfonamide) inhibitors. One of
      these inhibitors was synthesized in the absence of the DNA-tag and showed
      accumulation in hypoxic tumor tissue sections in vitro and tumor targeting in
      vivo.

PMID- 21186832
TI  - Two-dimensional molecular crystals of phosphonic acids on graphene.
AB  - The synthesis and characterization of two-dimensional (2D) molecular crystals
      composed of long and linear phosphonic acids atop graphene is reported. Using
      scanning probe microscopy in combination with first-principles calculations, we
      show that these true 2D crystals are oriented along the graphene armchair
      direction only, thereby enabling an easy determination of graphene flake
      orientation. We have also compared the doping level of graphene flakes via Raman
      spectroscopy. The presence of the molecular crystal atop graphene induces a well
      defined shift in the Fermi level, corresponding to hole doping, which is in
      agreement with our ab initio calculations.

PMID- 21186834
TI  - Self-assembly of a metallomacrocycle templated by iron(II).
AB  - An unusual discrete heteronuclear metallomacrocycle was designed and synthesized
      via metal-ion-directed self-assembly by an iron(II) template. The formation of
      this metallomacrocycle was demonstrated by X-ray crystallography, electrospray
      ionization Fourier transform ion cyclotron resonance mass spectrometry, and NMR
      spectroscopy.

PMID- 21186833
TI  - Maleimide photolithography for single-molecule protein-protein interaction
      analysis in micropatterns.
AB  - Spatial organization of proteins into microscopic structures has important
      applications in fundamental and applied research. Preserving the function of
      proteins in such microstructures requires generic methods for site-specific
      capturing through affinity handles. Here, we present a versatile bottom-up
      surface micropatterning approach based on surface functionalization with
      maleimides, which selectively react with organic thiols. Upon UV irradiation
      through a photomask, the functionality of illuminated maleimide groups was
      efficiently destroyed. Remaining maleimides in nonilluminated regions were
      further reacted with different thiol-functionalized groups for site-specific
      protein immobilization under physiological conditions. Highly selective
      immobilization of His-tagged proteins into tris(nitrilotriacetic acid)
      functionalized microstructures with very high contrast was possible even by
      direct capturing of proteins from crude cell lysates. Moreover, we employed
      phosphopantetheinyl transfer from surface-immobilized coenzyme A to ybbR-tagged
      proteins in order to implement site-specific, covalent protein immobilization
      into microstructures. The functional integrity of the immobilized protein was
      confirmed by monitoring protein-protein interactions in real time. Moreover, we
      demonstrate quantitative single-molecule analysis of protein-protein interactions
      with proteins selectively captured into these high-contrast micropatterns.

PMID- 21186835
TI  - Proteomic profiling of human plasma by iTRAQ reveals down-regulation of ITI-HC3
      and VDBP by cigarette smoking.
AB  - Biomarkers in noninvasive fluids indicative of cigarette smoke's effects are
      urgently needed. In this pilot study, we utilized the proteomic approach,
      isobaric Tags for Relative and Absolute Quantitation (iTRAQ), to identify
      differentially expressed plasma proteins in healthy cigarette smokers compared to
      healthy nonsmokers; select proteins were further confirmed by immunoblot
      analysis. Significant, differentially expressed proteins identified in the plasma
      separated subjects based on their condition as smokers or nonsmokers. Several of
      the proteins identified in this study are associated with immunity and
      inflammatory responses and have been shown to be associated with tobacco-related
      diseases, including chronic obstructive pulmonary disease (COPD) and lung cancer.
      Proteins up-regulated in smokers included complement component 8 polypeptide
      chains alpha, beta, and gamma, and mannose-binding protein C, and proteins down
      regulated included inter-alpha-trypsin inhibitor heavy chain H3 (ITI-HC3) and
      vitamin D-binding protein (VDBP). In addition, gelsolin and vitronectin, known
      tissue leakage proteins, were up- and down-regulated, respectively. Our results
      demonstrate for the first time that chronic cigarette smoking can influence the
      expression profile of the human plasma proteome. Proteins identified in this
      pilot study may serve as candidate biomarkers of diseases resulting from exposure
      to cigarette smoke in future molecular epidemiological studies.

PMID- 21186836
TI  - The most important promise ever made.

PMID- 21186837
TI  - Environmental policy: past, present, and future.

PMID- 21186839
TI  - A rich vein? Mining and the pursuit of sustainability.

PMID- 21186842
TI  - A conversation with Dr. Phaedon Avouris: nanoscience leader. Interview by Paul S.
      Weiss.

PMID- 21186843
TI  - Exploiting topographical texture to impart icephobicity.
AB  - Appropriately structured topographical features that are found in nature (e.g,,
      the lotus leaf) or that are produced synthetically (e.g., via lithography) can
      impart superhydrophobic properties to surfaces. Water beads up and readily rolls
      off of such surfaces, making them self-cleaning. Within the past few years,
      scientists and engineers have begun exploring the utility of these surfaces in
      mitigating the icing problem prevalent in the operation of critical
      infrastructure such as airplanes, ships, power lines, and telecommunications
      equipment. An article in this issue advances our fundamental knowledge in this
      area by examining the dynamic impact of water droplets on both smooth and
      topographically structured supercooled substrates. The results illustrate that,
      under at least some environmental conditions, superhydrophobic surfaces can
      minimize or even eliminate ice formation by repelling impinging water drops
      before they can freeze. Subsequent research will build on these results, possibly
      leading to the fabrication of commercially viable and durable icephobic surfaces
      that mitigate the icing problem under all environmental conditions.

PMID- 21186844
TI  - Electronic transport between graphene layers covalently connected by carbon
      nanotubes.
AB  - We present a first-principles study of the electronic transport properties of
      metallic and semiconducting carbon nanotube (CNT) junctions connecting two
      graphene layers, for different CNT lengths and link structures. Transport is
      analyzed in terms of the scattering states originated from the pi and pi* states
      of the finite-length CNTs, which couple to the graphene states producing
      resonances in the transmission curves. We find that, for metallic CNTs, the
      conductance is nearly independent of the tube length, but changes strongly with
      the link structure, while the opposite occurs for semiconducting CNTs, where the
      conductance in the tunneling regime is mainly controlled by the tube length and
      independent of the link structure. The sizable band offset between graphene and
      the CNTs yields to considerable effects on the transport properties, which cannot
      be captured using simple empirical models and highlights the need for a first
      principles description.

PMID- 21186845
TI  - LC-MS based serum metabonomic analysis for renal cell carcinoma diagnosis,
      staging, and biomarker discovery.
AB  - A LC-MS based method, which utilizes both reversed-performance (RP)
      chromatography and hydrophilic interaction chromatography (HILIC) separations,
      has been carried out in conjunction with multivariate data analysis to
      discriminate the global serum profiles of renal cell carcinoma (RCC) patients and
      healthy controls. The HILIC was found necessary for a comprehensive serum
      metabonomic profiling as well as RP separation. The feasibility of using serum
      metabonomics for the diagnosis and staging of RCC has been evaluated. One-hundred
      percent sensitivity in detection has been achieved, and a satisfactory clustering
      between the early stage and advanced-stage patients is observed. The results
      suggest that the combination of LC-MS analysis with multivariate statistical
      analysis can be used for RCC diagnosis and has potential in the staging of RCC.
      The MS/MS experiments have been carried out to identify the biomarker patterns
      that made great contribution to the discrimination. As a result, 30 potential
      biomarkers for RCC are identified. It is possible that the current biomarker
      patterns are not unique to RCC but just the result of any malignancy disease. To
      further elucidate the pathophysiology of RCC, related metabolic pathways have
      been studied. RCC is found to be closely related to disturbed phospholipid
      catabolism, sphingolipid metabolism, phenylalanine metabolism, tryptophan
      metabolism, fatty acid beta-oxidation, cholesterol metabolism, and arachidonic
      acid metabolism.

PMID- 21186846
TI  - Quantitative secretome analysis reveals that COL6A1 is a metastasis-associated
      protein using stacking gel-aided purification combined with iTRAQ labeling.
AB  - In cancer metastasis, secreted proteins play an important role in promoting
      cancer cell migration and invasion and thus also in the increase of cancer
      metastasis in the extracellular microenvironment. In this study, we developed a
      strategy that combined a simple gel-aided protein purification with iTRAQ
      labeling to quantify and discover the metastasis-associated proteins in the lung
      cancer cell secretome. Secreted proteins associated with lung cancer metastasis
      were produced using CL1-0 and CL1-5 cells with different metastatic abilities.
      Quantitative secretomics analysis identified a total of 353 proteins, 7 of which
      were considered to be metastasis-associated proteins. These included TIMP1,
      COL6A1, uPA, and AAT, all of which were higher in CL1-5, and AL1A1, PRDX1, and
      NID1, which were higher in CL1-0. Six of these metastasis-associated proteins
      were validated with Western blot analysis. In addition, pathway analysis was
      performed in building the interaction network between the identified metastasis
      associated proteins. Further functional analysis of COL6A1 on the metastatic
      abilities of CL1 cells was also carried out. An RNA interference-based knock-down
      of COL6A1 suppressed the metastatic ability of CL1-5 cells; in contrast, a
      plasmid-transfected overexpression of COL6A1 increased the metastatic ability of
      CL1-0 cells. This study describes a simple and high throughput sample
      purification method that can be used for the quantitative secretomics analysis of
      metastasis-associated proteins.

PMID- 21186847
TI  - Communication: Hybrid ensembles for improved force matching.
AB  - Force matching is a method for parameterizing empirical potentials in which the
      empirical parameters are fitted to a reference potential energy surface (PES).
      Typically, training data are sampled from a canonical ensemble generated with
      either the empirical potential or the reference PES. In this Communication, we
      show that sampling from either ensemble risks excluding critical regions of
      configuration space, leading to fitted potentials that deviate significantly from
      the reference PES. We present a hybrid ensemble which combines the Boltzmann
      probabilities of both potential surfaces into the fitting procedure, and we
      demonstrate that this technique improves the quality and stability of empirical
      potentials.

PMID- 21186848
TI  - Communication: Direct observation of a hydrophobic bond in loop closure of a
      capped (-OCH2CH2-)n oligomer in water.
AB  - The small r variation of the probability density P(r) for end-to-end separations
      of a -CH(2)CH(3) capped (-OCH(2)CH(2)-)(n) oligomer in water is computed to be
      closely similar to the CH(4)...CH(4) potential of mean force under the same
      circumstances. Since the aqueous solution CH(4)...CH(4) potential of mean force
      is the natural physical definition of a primitive hydrophobic bond, the present
      result identifies an experimentally accessible circumstance for direct
      observation of a hydrophobic bond which has not been observed previously because
      of the low solubility of CH(4) in water. The physical picture is that the soluble
      chain molecules carry the capping groups into aqueous solution, and permits them
      to find one another with reasonable frequency. Comparison with the corresponding
      results without the solvent shows that hydration of the solute oxygen atoms
      swells the chain molecule globule. This supports the view that the chain molecule
      globule might have a secondary effect on the hydrophobic interaction that is of
      first interest here. The volume of the chain molecule globule is important for
      comparing the probabilities with and without solvent because it characterizes the
      local concentration of capping groups. Study of other capping groups to enable x
      ray and neutron diffraction measurements of P(r) is discussed.

PMID- 21186849
TI  - Communication: Hilbert-space partitioning of the molecular one-electron density
      matrix with orthogonal projectors.
AB  - A double-atom partitioning of the molecular one-electron density matrix is used
      to describe atoms and bonds. All calculations are performed in Hilbert space. The
      concept of atomic weight functions (familiar from Hirshfeld analysis of the
      electron density) is extended to atomic weight matrices. These are constructed to
      be orthogonal projection operators on atomic subspaces, which has significant
      advantages in the interpretation of the bond contributions. In close analogy to
      the iterative Hirshfeld procedure, self-consistency is built in at the level of
      atomic charges and occupancies. The method is applied to a test set of about 67
      molecules, representing various types of chemical binding. A close correlation is
      observed between the atomic charges and the Hirshfeld-I atomic charges.

PMID- 21186850
TI  - Communication: Emergence of localized magnetic moment at adsorbed beryllium dimer
      on graphene.
AB  - Graphene with significant and stable magnetic moment is expected to have various
      promising applications in electronics. The conventional way to magnetize graphene
      is to dope paramagnetic adsorbates onto it. However, this method usually induces
      fractional charge transfer, which decreases the total magnetic moment. Contrary
      to the conventional way and widely held point of view that diamagnetic adsorbates
      are weak dopants, for the first time we report our theoretical findings that
      doping the diamagnetic beryllium dimer on perfect diamagnetic graphene produces a
      stable system with a local magnetic moment as large as 1 MU(B). It is revealed
      that this process is realized through the spin-polarized electron transfer.

PMID- 21186851
TI  - Communication: Rotational excitation of interstellar heavy water by hydrogen
      molecules.
AB  - Cross sections and rate coefficients for low lying rotational transitions in
      D(2)O induced by para-H(2) collisions are presented for the first time.
      Calculations have been performed at the close-coupling level with the deuterated
      variant of the H(2)O-H(2) interaction potential of Valiron et al. [J. Chem. Phys.
      129, 134306 (2008)]. Rate coefficients are presented for temperatures between 1
      and 30 K and are compared to the corresponding rate coefficients for H(2)O.
      Significant differences caused by the isotopic substitution are observed and are
      attributed to both kinematics and intramolecular geometry effects. Astrophysical
      implications are briefly discussed in view of the very recent detection of D(2)O
      by the Herschel Space Observatory.

PMID- 21186852
TI  - The polarizable point dipoles method with electrostatic damping: implementation
      on a model system.
AB  - Recently, the use of polarizable force fields in Molecular Dynamics simulations
      has been gaining importance, since they allow a better description of
      heterogeneous systems compared to simple point charges force fields. Among the
      various techniques developed in the last years the one based on polarizable point
      dipoles represents one of the most used. In this paper, we review the basic
      technical issues of the method, illustrating the way to implement intramolecular
      and intermolecular damping of the electrostatic interactions, either with and
      without the Ewald summation method. We also show how to reduce the computational
      overhead for evaluating the dipoles, introducing to the state-of-the-art methods:
      the extended Lagrangian method and the always stable predictor corrector method.
      Finally we discuss the importance of screening the electrostatic interactions at
      short range, defending this technique against simpler approximations usually
      made. We compare results of density functional theory and classical force field
      based Molecular Dynamics simulations of chloride in water.

PMID- 21186853
TI  - Benchmark studies of variational, unitary and extended coupled cluster methods.
AB  - Comparative benchmark calculations are presented for coupled cluster theory in
      its standard formulation, as well as variational, extended, and unitary coupled
      cluster methods. The systems studied include HF, N(2), and CN, and with cluster
      operators that for the first time include up to quadruple excitations. In cases
      where static correlation effects are weak, the differences between the
      predictions of molecular properties from each theory are negligible. When,
      however, static correlation is strong, it is demonstrated that variational
      coupled cluster theory can be significantly more robust than the traditional
      ansatz and offers a starting point on which to base single-determinant reference
      methods that can be used beyond the normal domain of applicability. These
      conclusions hold at all levels of truncation of the cluster operator, with the
      variational approach showing significantly smaller errors.

PMID- 21186854
TI  - Exact quantum statistics for electronically nonadiabatic systems using continuous
      path variables.
AB  - We derive an exact, continuous-variable path integral (PI) representation of the
      canonical partition function for electronically nonadiabatic systems. Utilizing
      the Stock-Thoss (ST) mapping for an N-level system, matrix elements of the
      Boltzmann operator are expressed in Cartesian coordinates for both the nuclear
      and electronic degrees of freedom. The PI discretization presented here properly
      constrains the electronic Cartesian coordinates to the physical subspace of the
      mapping. We numerically demonstrate that the resulting PI-ST representation is
      exact for the calculation of equilibrium properties of systems with coupled
      electronic and nuclear degrees of freedom. We further show that the PI-ST
      formulation provides a natural means to initialize semiclassical trajectories for
      the calculation of real-time thermal correlation functions, which is numerically
      demonstrated in applications to a series of nonadiabatic model systems.

PMID- 21186855
TI  - DNA electrophoresis in confined, periodic geometries: a new lakes-straits model.
AB  - We present a method to study the dynamics of long DNA molecules inside a cubic
      array of confining spheres, connected through narrow openings. Our method is
      based on the coarse-grained, lakes-straits model of Zimm and is therefore much
      faster than Brownian dynamics simulations. In contrast to Zimm's approach, our
      method uses a standard stochastic kinetic simulation to account for the mass
      transfer through the narrow straits and the formation of new lakes. The different
      rates, or propensities, of the reactions are obtained using first-passage time
      statistics and a Monte Carlo sampling to compute the total free energy of the
      chain. The total free energy takes into account the self-avoiding nature of the
      chain as well as confinement effects from the impenetrable spheres. The
      mobilities of various chains agree with biased reptation theory at low and high
      fields. At moderate fields, confinement effects lead to a new regime of reptation
      where the mobility is a linear function of molecular weight and the dispersion is
      minimal.

PMID- 21186856
TI  - The renormalized Jellium model of colloidal suspensions with multivalent
      counterions.
AB  - An extension of the renormalized Jellium model which allows to study colloidal
      suspensions containing trivalent counterions is proposed. The theory is based on
      a modified Poisson-Boltzmann equation which incorporates the effects of
      counterion correlations near the colloidal surfaces using a new boundary
      condition. The renormalized charges, the counterion density profiles, and osmotic
      pressures can be easily calculated using the modified renormalized Jellium model.
      The results are compared with the ones obtained using the traditional Wigner
      Seitz (WS) cell approximation also with a new boundary condition. We find that
      while the thermodynamic functions obtained within the renormalized Jellium model
      are in a good agreement with their WS counterpart, the effective charges
      predicted by the two theories can be significantly different.

PMID- 21186857
TI  - A coupled cluster approach with a hybrid treatment of connected triple
      excitations: implementation and applications for open-shell systems.
AB  - An implementation of the coupled cluster (CC) singles, doubles, and a hybrid
      treatment of connected triples [denoted as CCSD(T)-h], based on the unrestricted
      Hartree-Fock (UHF) reference, is presented. Based on the spin-integrated
      formulation, we have developed a computer program to achieve the automatic
      derivation and implementation of the CCSD(T)-h approach. The CCSD(T)-h approach
      computationally scales as the seventh power of the system size, and is affordable
      for many medium-sized systems. The present approach has been applied to study the
      equilibrium geometries and harmonic vibrational frequencies in a number of open
      shell diatomic molecules and bond breaking potential energy profiles in several
      open-shell molecules, including CH(3), NH(2), and SiH(2). For all systems under
      study, the overall performance of the UHF-based CCSD(T)-h approach is very close
      to that of the corresponding CCSDT (CC singles, doubles, and triples), and much
      better than that of the UHF-based CCSD(T) (CC singles, doubles, and perturbative
      triples).

PMID- 21186858
TI  - Discrete perturbation theory applied to Lennard-Jones and Yukawa potentials.
AB  - Discrete perturbation theory (DPT) is a powerful tool to study systems
      interacting with potentials that are continuous but can be approximated by a
      piecewise continuous function composed of horizontal segments. The main goal of
      this work is to analyze the effect of several variables to improve the
      representation of continuous potentials in order to take advantage of DPT. The
      main DPT parameters chosen for the purpose are the starting location and size of
      the horizontal segments used to divide the full range of the potential and its
      maximum reach. We also studied the effect of having each segment aligned to the
      left, to the right, or centered on the continuous function. The properties
      selected to asses the success of this strategy are the orthobaric densities and
      their corresponding critical points. Critical parameters and orthobaric densities
      were evaluated by DPT for each of an ample set of variables and compared with
      their values calculated via discontinuous molecular dynamics. The best sets of
      DPT parameters are chosen so as to give equations of state that represent
      accurately the Lennard-Jones and Yukawa fluids.

PMID- 21186859
TI  - Exploiting classical nucleation theory for reverse self-assembly.
AB  - In this paper we introduce a new method to design interparticle interactions to
      target arbitrary crystal structures via the process of self-assembly. We show
      that it is possible to exploit the slope of the crystal nucleation free-energy
      barrier to sample and select optimal interparticle interactions for self-assembly
      into a desired structure. We apply this method to find interactions to target two
      simple crystal structures: a crystal with simple cubic symmetry and a two
      dimensional plane with square symmetry embedded in a three-dimensional space.
      Finally, we discuss the potential and limits of our method and propose a general
      model by which a functionally infinite number of different interaction geometries
      may be constructed and to which our reverse self-assembly method could in
      principle be applied.

PMID- 21186860
TI  - General implementation of the relativistic coupled-cluster method.
AB  - We report the development of a general order relativistic coupled-cluster (CC)
      code. Our implementation is based on Kramers-paired molecular spinors, utilizes
      double group symmetry, and is applicable with the full Dirac-Coulomb and several
      approximate relativistic Hamiltonians. The available methods include iterative
      and perturbative single-reference CC approaches with arbitrary excitations as
      well as a state-selective multi-reference CC ansatz. To illustrate the
      performance of the new code, benchmark calculations have been performed for the
      total energies, bond lengths, and vibrational frequencies of the monoxides of
      Group IVa elements. The trends due to the simultaneous inclusion of relativity as
      well as higher-order electron correlation effects are analyzed. The newly
      developed code significantly widens the scope of the ab initio relativistic
      calculations, for both molecules and atoms alike, surpassing the accuracy and
      reliability of the currently available implementations in the literature.

PMID- 21186861
TI  - Inclusion of selected higher excitations involving active orbitals in the state
      specific multireference coupled-cluster theory.
AB  - The parent state-specific multireference coupled-cluster (SS-MRCC) theory
      proposed by Mukherjee et al. [J. Chem. Phys. 110, 6171 (1999)], though rigorously
      size-extensive and also size-consistent with localized orbitals, has some
      deficiencies in the minimal truncation scheme, viz. at the singles and doubles
      (SD) level (SS-MRCCSD). SS-MRCCSD does not involve the direct coupling of all the
      model functions with a given virtual function belonging to the uncontracted
      multiconfiguration CISD space. It also does not involve, even in the linear power
      of a cluster operator T(MU), the direct coupling of the virtual functions
      chi(l(MU)), which are up to doubly excited with respect to a model function
      phi(MU) to the other virtual functions of the MRCISD space which can be generated
      by triple and quadruple excitations from phi(MU). We argue that inclusion of a
      selection of triples and quadruples involving at most two inactive orbital
      excitations from every phi(MU) would ameliorate the shortcoming of the incomplete
      coupling of the triply and quadruply excited virtual functions which can couple
      with the singly and doubly excited ones. This extended ansatz for our SS-MRCC
      theory, to be called SS-MRCCSDtq by us, would still miss the direct coupling of
      the manifold of the model functions {phi(lambda),lambda ? MU} to singly and
      doubly excited virtual functions. However, this effect is expected to be less
      significant than the lack of the more complete virtual space couplings, these
      functions being many more numerous, suggesting the new methods to be
      significantly improved schemes. Excellent results on the potential energy
      surfaces of small molecules involving single, double, and triple bond
      dissociation bear out our expectations fully.

PMID- 21186862
TI  - Algorithmic differentiation and the calculation of forces by quantum Monte Carlo.
AB  - We describe an efficient algorithm to compute forces in quantum Monte Carlo using
      adjoint algorithmic differentiation. This allows us to apply the space warp
      coordinate transformation in differential form, and compute all the 3M force
      components of a system with M atoms with a computational effort comparable with
      the one to obtain the total energy. Few examples illustrating the method for an
      electronic system containing several water molecules are presented. With the
      present technique, the calculation of finite-temperature thermodynamic properties
      of materials with quantum Monte Carlo will be feasible in the near future.

PMID- 21186863
TI  - Systematic investigation of global phase behavior of polymer mixtures in the
      pressure-temperature plane.
AB  - We investigate the critical lines of polymer mixtures in the presence of their
      vapor phase at the mathematical double point, where two critical lines meet and
      exchange branches, and its environment. The model used combines the lattice gas
      model of Schouten, ten Seldam and Trappeniers with the Flory-Huggins theory. The
      critical line structure is displayed for various combinations of the chain length
      and system parameters in the pressure (P)-temperature (T) plane, as is usually
      done with experimental results. This type of work sheds light on the essential
      transition mechanism involved in the phase diagram's change of character, such as
      multi-critical points and mathematical double points, which are of great
      practical importance in supercritical fluid extraction processes. The P, T
      diagrams are discussed in accordance with the Scott and van Konynenburg binary
      phase diagram classification. We found that our P, T plots were in agreement with
      type II, type III, or type IV phase diagram behaviors. We also found that some of
      our phase diagrams represent the liquid-liquid equilibria in polymer solutions
      and mixtures.

PMID- 21186864
TI  - Charge density identification in ion channels.
AB  - Biological channels permeate ions through cell membranes. Ion channels carry a
      permanent charge that has a significant role in determining channel's permeation
      properties such as selectivity to certain ions, current amplitude, etc. In this
      paper we deal with the determination of the permanent charge from current-voltage
      curves. The ion channel current behavior is modelled by Poisson-Nernst-Planck
      (PNP) equations system. Previous works on the fixed charge density identification
      problem contain several ill-posed steps and linearization of the nonlinear PNP
      system. We suggest here several methods to make these algorithms more stable and
      accurate.

PMID- 21186865
TI  - Rotational dependence of the proton-transfer reaction HBr+ + CO2 -> HOCO+ + Br.
      II. Comparison of HBr+ (2Pi(3/2)) and HBr+ (2Pi(1/2)).
AB  - The effects of reactant ion rotational excitation on the exothermic proton
      transfer reactions of HBr(+)((2)Pi(1/2)) and DBr(+)((2)Pi(1/2)), respectively,
      with CO(2) were studied in a guided ion beam apparatus. Cross sections are
      presented for collision energies in the center of mass system E(c.m.) in the
      range of 0.23 to 1.90 eV. The HBr(+)/DBr(+) ions were prepared in a state
      selective manner by resonance enhanced multiphoton ionization. The mean
      rotational energy was varied from 3.4 to 46.8 meV for HBr(+)((2)Pi(1/2)) and from
      1.8 to 40.9 meV for DBr(+)((2)Pi(1/2)). Both reactions studied are inhibited by
      collision energy, as expected for exothermic reactions. For all collision
      energies considered, the cross section decreases with increasing rotational
      energy of the ion, but the degree of the rotational dependence differs depending
      on the collision energy. For E(c.m.) = 0.31 eV, the cross sections of the
      deuteron transfer are significantly larger than those of the proton transfer. For
      higher E(c.m.) they differ very little. The current results for the exothermic
      proton transfer are systematically compared to previously published data for the
      endothermic proton transfer starting from HBr(+)((2)Pi(3/2)) [L. Paetow et al.,
      J. Chem. Phys. 132, 174305 (2010)]. Additional new data regarding the latter
      reaction are presented to further confirm the conclusions. The dependences on
      rotational excitation found cannot be explained by the corresponding change in
      the total energy of the system. For both the endothermic and the exothermic
      reaction, the cross section is maximized for the smallest rotational energy, at
      least well above the threshold.

PMID- 21186866
TI  - Recombination-pumped triatomic hydrogen infrared lasers.
AB  - Mid-infrared laser lines observed in hydrogen/rare gas discharges are assigned to
      three-body recombination processes involving an electron, a rare gas (He or Ne)
      atom, and the triatomic hydrogen ion (H(3)(+)). Calculations of radiative
      transitions between neutral H(3) Rydberg states support this interpretation, and
      link it to recent results for hydrogenic/rare gas afterglow plasmas. A mechanism
      for the population inversion is proposed, and the potential generality and
      astrophysical implications of such molecular recombination laser systems are
      briefly discussed.

PMID- 21186867
TI  - Ultrafast photodynamics of furan.
AB  - Ultrafast photodynamics of furan has been studied by time-resolved photoelectron
      imaging (TRPEI) spectroscopy with an unprecedented time resolution of 22 fs. The
      simulation of the time-dependent photoelectron kinetic energy distribution (PKED)
      has been performed with ab initio nonadiabatic dynamics "on the fly" in the frame
      of time-dependent density functional theory. Based on the agreement between
      experimental and theoretical time-dependent photoelectron signal intensity as
      well as on PKED, precise time scales of ultrafast internal conversion from S(2)
      over S(1) to the ground state S(0) of furan have been revealed for the first
      time. Upon initial excitation of the S(2) state which has pi-pi* character, a
      nonadiabatic transition to the S(1) state occurs within 10 fs. Subsequent
      dynamics invokes the excitation of the C-O stretching and C-O-C out of plane
      vibrations which lead to the internal conversion to the ground state after 60 fs.
      Thus, we demonstrate that the TRPEI combined with high level nonadiabatic
      dynamics calculations provide fundamental insight into ultrafast photodynamics of
      chemically and biologically relevant chromophores.

PMID- 21186868
TI  - Kinetics following addition of sulfur fluorides to a weakly ionized plasma from
      300 to 500 K: rate constants and product determinations for ion-ion mutual
      neutralization and thermal electron attachment to SF5, SF3, and SF2.
AB  - Rate constants for several processes including electron attachment to SF(2),
      SF(3), and SF(5) and individual product channels of ion-ion mutual neutralization
      between SF(6)(-), SF(5)(-), and SF(4)(-) with Ar(+) were determined by variable
      electron and neutral density attachment mass spectrometry. The experiments were
      conducted with a series of related neutral precursors (SF(6), SF(4), SF(5)Cl,
      SF(5)C(6)H(5), and SF(3)C(6)F(5)) over a temperature range of 300-500 K. Mutual
      neutralization rate constants for SF(6)(-), SF(5)(-), and SF(4)(-) with Ar(+) are
      reported with uncertainties of 10-25% and show temperature dependencies in
      agreement with the theoretical value of T(-0.5). Product branching in the mutual
      neutralizations is temperature independent and dependent on the electron binding
      energy of the anion. A larger fraction of product neutrals from the SF(6)(-)
      mutual neutralization (0.9 +/- 0.1) are dissociated than in the SF(5)(-) mutual
      neutralization (0.65 +/- 0.2), with the SF(4)(-) (0.7 +/- 0.3) likely lying in
      between. Electron attachment to SF(5) (k = 2.0 * 10(-8) +/-(1)(2) cm(3) s(-1) at
      300 K) and SF(3) (4 +/- 3 * 10(-9) cm(3) s(-1) at 300 K) show little temperature
      dependence. Rate constants of electron attachment to closed-shell SF(n) species
      decrease as the complexity of the neutral decreases.

PMID- 21186869
TI  - Resistances for heat and mass transfer through a liquid-vapor interface in a
      binary mixture.
AB  - In this paper we calculate the interfacial resistances to heat and mass transfer
      through a liquid-vapor interface in a binary mixture. We use two methods, the
      direct calculation from the actual nonequilibrium solution and integral
      relations, derived earlier. We verify, that integral relations, being a
      relatively faster and cheaper method, indeed gives the same results as the direct
      processing of a nonequilibrium solution. Furthermore we compare the absolute
      values of the interfacial resistances with the ones obtained from kinetic theory.
      Matching the diagonal resistances for the binary mixture we find that kinetic
      theory underestimates the cross coefficients. The heat of transfer is, as a
      consequence, correspondingly larger.

PMID- 21186870
TI  - Widom line and the liquid-liquid critical point for the TIP4P/2005 water model.
AB  - The Widom line and the liquid-liquid critical point of water in the deeply
      supercooled region are investigated via computer simulation of the TIP4P/2005
      model. The Widom line has been calculated as the locus of compressibility maxima.
      It is quite close to the experimental homogeneous nucleation line and, in the
      region studied, it is almost parallel to the curve of temperatures of maximum
      density at fixed pressure. The critical temperature is determined by examining
      which isotherm has a region with flat slope. An interpolation in the Widom line
      gives the rest of the critical parameters. The computed critical parameters are
      T(c)=193 K, p(c)=1350 bar, and rho(c)=1.012 g/cm(3). Given the performance of the
      model for the anomalous properties of water and for the properties of ice phases,
      the calculated critical parameters are probably close to those of real water.

PMID- 21186871
TI  - Electronic structure and the glass transition in pnictide and chalcogenide
      semiconductor alloys. I. The formation of the ppsigma-network.
AB  - Semiconductor glasses exhibit many unique optical and electronic anomalies. We
      have put forth a semiphenomenological scenario [A. Zhugayevych and V. Lubchenko,
      J. Chem. Phys. 133, 234504 (2010)] in which several of these anomalies arise from
      deep midgap electronic states residing on high-strain regions intrinsic to the
      activated transport above the glass transition. Here we demonstrate at the
      molecular level how this scenario is realized in an important class of
      semiconductor glasses, namely chalcogen and pnictogen containing alloys. Both the
      glass itself and the intrinsic electronic midgap states emerge as a result of the
      formation of a network composed of sigma-bonded atomic p-orbitals that are only
      weakly hybridized. Despite a large number of weak bonds, these ppsigma-networks
      are stable with respect to competing types of bonding, while exhibiting a high
      degree of structural degeneracy. The stability is rationalized with the help of a
      hereby proposed structural model, by which ppsigma-networks are symmetry-broken
      and distorted versions of a high symmetry structure. The latter structure
      exhibits exact octahedral coordination and is fully covalently bonded. The
      present approach provides a microscopic route to a fully consistent description
      of the electronic and structural excitations in vitreous semiconductors.

PMID- 21186872
TI  - Electronic structure and the glass transition in pnictide and chalcogenide
      semiconductor alloys. II. The intrinsic electronic midgap states.
AB  - We propose a structural model that treats in a unified fashion both the atomic
      motions and electronic excitations in quenched melts of pnictide and chalcogenide
      semiconductors. In Part I [A. Zhugayevych and V. Lubchenko, J. Chem. Phys. 133,
      234503 (2010)], we argued these quenched melts represent aperiodic ppsigma
      networks that are highly stable and, at the same time, structurally degenerate.
      These networks are characterized by a continuous range of coordination. Here we
      present a systematic way to classify these types of coordination in terms of
      discrete coordination defects in a parent structure defined on a simple cubic
      lattice. We identify the lowest energy coordination defects with the intrinsic
      midgap electronic states in semiconductor glasses, which were argued earlier to
      cause many of the unique optoelectronic anomalies in these materials. In
      addition, these coordination defects are mobile and correspond to the transition
      state configurations during the activated transport above the glass transition.
      The presence of the coordination defects may account for the puzzling discrepancy
      between the kinetic and thermodynamic fragility in chalcogenides. Finally, the
      proposed model recovers as limiting cases several popular types of bonding
      patterns proposed earlier including: valence-alternation pairs, hypervalent
      configurations, and homopolar bonds in heteropolar compounds.

PMID- 21186873
TI  - Influence of confinement on solvation of ethanol in water studied by Raman
      spectroscopy.
AB  - Herewith we present the results of our studies on the effect of confinement on
      the solvation of ethyl alcohol in aqueous solutions using Raman spectroscopy of
      the O-H stretching band. Based on Gaussian-Lorentzian deconvolution of the O-H
      band Raman spectra we investigate the local structures created between water
      water, water-alcohol, and alcohol-alcohol molecules, which are directly related
      to the solubility of the liquids. Comparison of the responses in bulk solutions
      and in solutions confined in the pores of the gelatin gel shows that for high
      ethanol concentrations solubility significantly increases with decrease of the
      pore sizes.

PMID- 21186874
TI  - Reduced mobility of di-propylene glycol methylether in its aqueous mixtures by
      quasielastic neutron scattering.
AB  - The hydrogen (H-) bonding interplay between water and other organic molecules is
      important both in nature and in a wide range of technological applications.
      Structural relaxation and, thus, diffusion in aqueous mixtures are generally
      dependent on both the strength and the structure of the H-bonds. To investigate
      diffusion in H-bonding mixtures, we present a quasielastic neutron scattering
      study of di-propylene glycol methylether (2PGME) mixed with H(2)O (or D(2)O) over
      the concentration range 0-90 wt.% water. We observe a nonmonotonic behavior of
      the dynamics with a maximum in average relaxation time for the mixture with 30
      wt.% water, which is more than a factor 2 larger compared to that of either of
      the pure constituents. This is a result in qualitative agreement with previous
      calorimetric studies and the behavior of aqueous mixtures of simple mono
      alcohols. More surprisingly, we notice that the dynamics of the 2PGME molecules
      in the mixture is slowed down by more than a factor 3 at 30 wt.% water but that
      the water dynamics indicates an almost monotonous behavior. Furthermore, in the
      low momentum transfer (Q) range of the 2PGME, where the intermediate scattering
      function I(Q,t) is considerably stretched in time (i.e., the stretching parameter
      beta ? 1), it is evident for the 2PGME-D(2)O samples that the Q-dependence of the
      inverse average relaxation time, <tau>(-1), is greater than 2. This implies that
      the relaxation dynamics is partly homogenously stretched, i.e., the relaxation of
      each relaxing unit is somewhat intrinsically stretched in time.

PMID- 21186875
TI  - Long range dipole-dipole correlations in nitrobenzene-benzene solutions.
AB  - Hyper-Rayleigh scattering (HRS) from liquid nitrobenzene-benzene solutions with
      nitrobenzene mole fraction in the range 0.001 < x(NB) < 1 was measured for
      several combinations of linear polarized incident and scattered light, for
      scattering angles near 90 degrees . Polar collective modes are identified by
      their distinctive HRS polarization dependence. At all concentrations the
      nitrobenzene HRS intensity is dominated by the transverse polar collective mode
      contribution and the longitudinal collective mode contribution is near zero. The
      transverse polar mode HRS is due to long range dipole-dipole orientation
      correlations between the nitrobenzene molecules, such that the molecular dipoles
      are oriented transverse to the wave vector for each spatial Fourier component of
      the orientation distribution.

PMID- 21186876
TI  - Melting in two-dimensional Yukawa systems: a Brownian dynamics simulation.
AB  - We studied the melting behavior of two-dimensional colloidal crystals with a
      Yukawa pair potential by Brownian dynamics simulations. The melting follows the
      Kosterlitz-Thouless-Halperin-Nelson-Young (KTHNY) scenario with two continuous
      phase transitions and a middle hexatic phase. The two phase-transition points
      were accurately identified from the divergence of the translational and
      orientational susceptibilities. Configurational temperatures were employed to
      monitor the equilibrium of the overdamped system and the strongest temperature
      fluctuation was observed in the hexatic phase. The inherent structure obtained by
      rapid quenching exhibits three different behaviors in the solid, hexatic, and
      liquid phases. The measured core energy of the free dislocations, E(c) = 7.81 +/-
      0.91 k(B)T, is larger than the critical value of 2.84 k(B)T, which consistently
      supports the KTHNY melting scenario.

PMID- 21186877
TI  - Electrical and ionic conductivity effects on magic-angle spinning nuclear
      magnetic resonance parameters of CuI.
AB  - We investigate experimentally and theoretically the effects of two different
      types of conductivity, electrical and ionic, upon magic-angle spinning NMR
      spectra. The experimental demonstration of these effects involves (63)Cu, (65)Cu,
      and (127)I variable temperature MAS-NMR experiments on samples of gamma-CuI, a
      Cu(+)-ion conductor at elevated temperatures as well as a wide bandgap
      semiconductor. We extend previous observations that the chemical shifts depend
      very strongly upon the square of the spinning-speed as well as the particular
      sample studied and the magnetic field strength. By using the (207)Pb resonance of
      lead nitrate mixed with the gamma-CuI as an internal chemical shift thermometer
      we show that frictional heating effects of the rotor do not account for the
      observations. Instead, we find that spinning bulk CuI, a p-type semiconductor due
      to Cu(+) vacancies in nonstoichiometric samples, in a magnetic field generates
      induced AC electric currents from the Lorentz force that can resistively heat the
      sample by over 200  degrees C. These induced currents oscillate along the rotor
      spinning axis at the spinning speed. Their associated heating effects are
      disrupted in samples containing inert filler material, indicating the existence
      of macroscopic current pathways between micron-sized crystallites. Accurate
      measurements of the temperature-dependence of the (63)Cu and (127)I chemical
      shifts in such diluted samples reveal that they are of similar magnitude (ca.
      0.27 ppm/K) but opposite sign (being negative for (63)Cu), and appear to depend
      slightly upon the particular sample. This relationship is identical to the
      corresponding slopes of the chemical shifts versus square of the spinning speed,
      again consistent with sample heating as the source of the observed large shift
      changes. Higher drive-gas pressures are required to spin samples that have higher
      effective electrical conductivities, indicating the presence of a braking effect
      arising from the induced currents produced by rotating a conductor in a
      homogeneous magnetic field. We present a theoretical analysis and finite-element
      simulations that account for the magnitude and rapid time-scale of the resistive
      heating effects and the quadratic spinning speed dependence of the chemical shift
      observed experimentally. Known thermophysical properties are used as inputs to
      the model, the sole adjustable parameter being a scaling of the bulk thermal
      conductivity of CuI in order to account for the effective thermal conductivity of
      the rotating powdered sample. In addition to the dramatic consequences of
      electrical conductivity in the sample, ionic conductivity also influences the
      spectra. All three nuclei exhibit quadrupolar satellite transitions extending
      over several hundred kilohertz that reflect defects perturbing the cubic symmetry
      of the zincblende lattice. Broadening of these satellite transitions with
      increasing temperature arises from the onset of Cu(+) ion jumps to sites with
      different electric field gradients, a process that interferes with the formation
      of rotational echoes. This broadening has been quantitatively analyzed for the
      (63)Cu and (65)Cu nuclei using a simple model in the literature to yield an
      activation barrier of 0.64 eV (61.7 kJ/mole) for the Cu(+) ion jumping motion
      responsible for the ionic conductivity that agrees with earlier results based on
      (63)Cu NMR relaxation times of static samples.

PMID- 21186878
TI  - Hard spheres revisited: accurate calculation of the solid-liquid interfacial free
      energy.
AB  - We revise the earlier [R. L. Davidchack and B. B. Laird, Phys. Rev. Lett. 85,
      4751 (2000)] direct calculation of the hard sphere solid-liquid interfacial free
      energy by the cleaving walls method. The revisions of the method include modified
      interactions with the cleaving walls and the use of a nonequilibrium work
      measurements approach, which allows for a more robust control of the accuracy of
      the obtained results. We find that the new values are lower compared to the
      original ones, which is consistent with the more recent indirect estimates based
      on extrapolation from the soft-sphere results [R. L. Davidchack and B. B. Laird,
      Phys. Rev. Lett. 94, 086102 (2005)], as well as those obtained using the
      capillary fluctuations method [R. L. Davidchack, J. R. Morris, and B. B. Laird,
      J. Chem. Phys. 125, 094710 (2006)].

PMID- 21186879
TI  - Sum-frequency generation of acetate adsorption on Au and Pt surfaces: molecular
      structure effects.
AB  - The reversible adsorption of acetate on polycrystalline Au and Pt surfaces was
      investigated with broadband sum-frequency generation (SFG) and cyclic
      voltammetry. Specifically adsorbed acetate as well as coadsorbed sulfuric acid
      anions are observed for the first time with SFG and give rise to dramatically
      different SFG intensities on Au and Pt surfaces. While similar coverages of
      acetate adlayers on Au and Pt surfaces are well established by previous studies,
      an identification of the interfacial molecular structure has been elusive.
      However, we have applied the high sensitivity of SFG for interfacial polar
      ordering to identify different acetate structures at Au and Pt surfaces in
      contact with HClO(4) and H(2)SO(4) electrolytes. Acetate competes with the
      formation of surface oxides and shifts the oxidation threshold of both Au and Pt
      electrodes anodically. Effects of the supporting electrolyte on the formation of
      acetate adlayers are revealed by comparing SFG spectra in HClO(4) and H(2)SO(4)
      solutions: Sulfuric acid anions modify the potential-dependent acetate
      adsorption, compete with adsorbed acetate on Au and coadsorb with acetate on Pt
      surfaces.

PMID- 21186880
TI  - Ion irradiation induced structural and electrical transition in graphene.
AB  - The relationship between the electrical properties and structure evolution of
      single layer graphene was studied by gradually introducing the gallium ion
      irradiation. Raman spectrums show a structural transition from nano-crystalline
      graphene to amorphous carbon as escalating the degree of disorder of the graphene
      sample, which is in correspondence with the electrical transition from a
      Boltzmann diffusion transport to a carrier hopping transport. The results show a
      controllable method to tune the properties of graphene.

PMID- 21186881
TI  - Time-resolved photoelectron spectroscopy of low-energy excitations of 4*4
      C60/Cu(111).
AB  - Time-resolved two-photon photoemission is applied to investigate electron
      dynamics in multiple monolayers (MLs) of ordered fullerite on a copper substrate.
      The experimental data are analyzed assuming coupled excited state dynamics. Rate
      equations fitted to these dynamics yield lifetimes of about 80 ps for the lowest
      unoccupied molecular orbital (LUMO), about 1.2 ns for the singlet exciton and 22
      MUs for the triplet exciton at a surface temperature of 140 K. For trapped
      triplet excitons lifetimes up to 200 MUs are observed. An increased excitation
      fluence reduces the lifetime of the excitons due to annihilation. An increased
      sample temperature slightly reduces the lifetime of the triplet exciton. There is
      no evident dependence of the exciton lifetimes on the pump photon energy in the
      range of hnu = 2.9 to 3.3 eV. A dependence on the layer thickness (10-20 ML) is
      not observed as long as more than 9 ML are prepared.

PMID- 21186882
TI  - Thermodynamic, electronic and structural properties of Cu/CeO2 surfaces and
      interfaces from first-principles DFT+U calculations.
AB  - The thermodynamic, structural and electronic properties of Cu-CeO(2) (ceria)
      surfaces and interfaces are investigated by means of density functional theory
      (DFT+U) calculations. We focus on model systems consisting of Cu atoms (i)
      supported by stoichiometric and reduced CeO(2) (111) surfaces, (ii) dispersed as
      substitutional solid solution at the same surface, as well as on (iii) the
      extended Cu(111)/CeO(2)(111) interface. Extensive charge reorganization at the
      metal-oxide contact is predicted for ceria-supported Cu adatoms and
      nanoparticles, leading to Cu oxidation, ceria reduction, and interfacial Ce(3+)
      ions. The calculated thermodynamics predict that Cu adatoms on stoichiometric
      surfaces are more stable than on O vacancies of reduced surfaces at all
      temperatures and pressures relevant for catalytic applications, even in extremely
      reducing chemical environments. This suggests that supported Cu nanoparticles do
      not nucleate at surface O vacancies of the oxide, at variance with many other
      metal/ceria systems. In oxidizing conditions, the solid solutions are shown to be
      more stable than the supported systems. Substitutional Cu ions form
      characteristic CuO(4) units. These promote an easy and reversible O release
      without the reduction of Ce ions. The study of the extended CeO(2)(111)/Cu(111)
      interface predicts the full reduction of the interfacial ceria trilayer. Cu
      nanoparticles supported by ceria are proposed to lie above a subsurface layer of
      Ce(3+) ions that extends up to the perimeter of the metal-oxide interface.

PMID- 21186883
TI  - Nucleation process in Cu3Au(001) surface region around the order-disorder phase
      transition.
AB  - The element distribution in the Cu(3)Au(001) surface region has been determined
      on the basis of directional Auger electron spectroscopy polar profiles
      measurements and interpreted in the frame of thermodynamic approach formulated
      for the inhomogeneous systems by using the Neel sublattices concept. Both
      approaches, experimental and theoretical, allowed us to present the temperature
      dependence of element concentration in a layer resolved mode. The wide
      temperature range explored in the experiment ensured the large data base for the
      theoretical analysis which enabled us to propose the distribution of intra-layer
      and inter-layer pairwise interactions leading to proper temperature dependence of
      segregation profiles in the surface region. This kind of interaction distribution
      can be understood as strain induced.

PMID- 21186884
TI  - Functionalization, self-assembly, and photoswitching quenching for azobenzene
      derivatives adsorbed on Au(111).
AB  - We have used scanning tunneling microscopy to investigate the structure and
      photoswitching behavior of azobenzene molecules functionalized with bulky spacer
      groups and adsorbed onto Au(111). We find that positioning tert-butyl "legs" in a
      canted arrangement on the azobenzene phenyl rings quenches photoisomerizability
      of the molecule on Au(111). Addition of cyano groups at the para positions
      changes the molecular self-assembly significantly, but does not alter the
      quenched photoisomerizability. This behavior likely arises from a combination of
      molecule-surface interactions, molecule-molecule interactions, and alteration of
      azobenzene electronic structure resulting from the position-specific addition of
      tert-butyl groups.

PMID- 21186885
TI  - Study of the heating effect contribution to the nonlinear dielectric response of
      a supercooled liquid.
AB  - We present a detailed study of the heating effects in dielectric measurements
      carried out on a liquid. Such effects come from the dissipation of the electric
      power in the liquid and give contribution to the nonlinear third harmonics
      susceptibility chi(3), which depends on the frequency and temperature. This study
      is used to evaluate a possible "spurious" contribution to the recently measured
      nonlinear susceptibility of an archetypical glassforming liquid (glycerol). Those
      measurements have been shown to give a direct evaluation of the number of
      dynamically correlated molecules temperature dependence close to the glass
      transition temperature T(g) ~ 190 K [Crauste-Thibierge et al., Phys. Rev. Lett.
      104, 165703 (2010)]. We show that the heating contribution is totally negligible
      (i) below 204 K at any frequency; (ii) for any temperature at the frequency where
      the third harmonics response chi(3) is maximum. Besides, this heating
      contribution does not scale as a function of f/f(alpha), with f(alpha)(T) the
      relaxation frequency of the liquid. In the high frequency range, when f/f(alpha)
      >= 1, we find that the heating contribution is damped because the dipoles cannot
      follow instantaneously the temperature modulation due to the heating phenomenon.
      An estimate of the magnitude of this damping is given.

PMID- 21186886
TI  - Shell structures of assemblies of equicharged particles subject to radial power
      law confining potentials.
AB  - Constituting the simplest generalization of spherical Coulomb crystals,
      assemblies of N equicharged particles confined by radial potentials proportional
      to the lambdath power of distance are amenable to rigorous analysis within the
      recently introduced shell model. Thanks to the power scaling of the confining
      potential and the resulting pruning property of the shell configurations (i.e.,
      the lists of shell occupancies), the shell-model estimates of the energies and
      the mean radii of such assemblies at equilibrium geometries follow simple
      recursive formulas. The formulas greatly facilitate derivations of the first two
      leading terms in the large-N asymptotics of these estimates, which are given by
      power series in xi(4/3) N(-2/3), where -(xi/2) n(3/2) is the leading angular
      correlation correction to the minimum energy of n electrons on the surface of a
      sphere with a unit radius (the solution of the Thomson problem). Although the
      scaled occupancies of the outermost shells conform to a universal scaling law,
      the actual filling of the shells tends to follow rather irregular patterns that
      vary strongly with lambda. However, the number of shells K(N) for a given N
      decreases in general upon an increase in the power-law exponent, which is due to
      the (lambda + 1)(2) xi(2) dependence of shell capacities that roughly measure the
      maximum numbers of particles sustainable within individual shells. Several types
      of configuration transitions (i.e., the changes in the number of shells upon
      addition of one particle) are observed in the crystals with up to 10,000
      particles and integer values of lambda between 1 and 10, but the rule |K(N + 1)
      K(N)| <= 1 is found to be strictly obeyed.

PMID- 21186887
TI  - On the phase behavior of hard aspherical particles.
AB  - We use numerical simulations to understand how random deviations from the ideal
      spherical shape affect the ability of hard particles to form fcc crystalline
      structures. Using a system of hard spheres as a reference, we determine the fluid
      solid coexistence pressures of both shape-polydisperse and monodisperse systems
      of aspherical hard particles. We find that when particles are sufficiently
      isotropic, the coexistence pressure can be predicted from a linear relation
      involving the product of two simple geometric parameters characterizing the
      asphericity of the particles. Finally, our results allow us to gain direct
      insight into the crystallizability limits of these systems by rationalizing
      empirical data obtained for analogous monodisperse systems.

PMID- 21186888
TI  - Three-dimensional Brownian diffusion of rod-like macromolecules in the presence
      of randomly distributed spherical obstacles: molecular dynamics simulation.
AB  - Brownian diffusion of rod-like polymers in the presence of randomly distributed
      spherical obstacles is studied using molecular dynamics simulations. It is
      observed that dependence of the reduced diffusion coefficient of these
      macromolecules on the available volume fraction can be described reasonably by a
      power law function. Despite the case of obstructed diffusion of flexible polymers
      in which reduced diffusion coefficient has a weak dependence on the polymer
      length, this dependence is noticeably strong in the case of rod-like polymers.
      Diffusion of these macromolecules in the presence of obstacles is observed that
      is anomalous at short time scales and normal at long times. Duration time of the
      anomalous diffusion regime is found that increases very rapidly with increasing
      both the polymer length and the obstructed volume fraction. Dynamics of diffusion
      of these polymers is observed that crosses over from Rouse to reptation type with
      increasing the density of obstacles.

PMID- 21186889
TI  - Hydrodynamic effects on spinodal decomposition kinetics in planar lipid bilayer
      membranes.
AB  - The formation and dynamics of spatially extended compositional domains in
      multicomponent lipid membranes lie at the heart of many important biological and
      biophysical phenomena. While the thermodynamic basis for domain formation has
      been explored extensively in the past, domain growth in the presence of
      hydrodynamic interactions both within the (effectively) two-dimensional membrane
      and in the three-dimensional solvent in which the membrane is immersed has
      received little attention. In this work, we explore the role of hydrodynamic
      effects on spinodal decomposition kinetics via continuum simulations of a
      convective Cahn-Hilliard equation for membrane composition coupled to the Stokes
      equation. Our approach explicitly includes hydrodynamics both within the planar
      membrane and in the three-dimensional solvent in the viscously dominated flow
      regime. Numerical simulations reveal that dynamical scaling breaks down for
      critical lipid mixtures due to distinct coarsening mechanisms for elongated
      versus more isotropic compositional lipid domains. The breakdown in scaling
      should be readily observable in experiments on model membrane systems.

PMID- 21186890
TI  - Hydrogen bond perturbation in hen egg white lysozyme by external electromagnetic
      fields: a nonequilibrium molecular dynamics study.
AB  - Nonequilibrium molecular dynamics simulations of a charge-neutral mutant of hen
      egg white lysozyme have been performed at 300 K and 1 bar in the presence of
      external microwave fields (2.45 to 100 GHz) of an rms electric field intensity of
      0.05 V A(-1). A systematic study was carried out of the distributions of
      persistence times and energies of each intraprotein hydrogen bond in between
      breakage and reformation, in addition to overall persistence over 20 ns
      simulations, vis-a-vis equilibrium, zero-field conditions. It was found that
      localized translational motion for formally charged residues led to greater
      disruption of associated hydrogen bonds, although induced rotational motion of
      strongly dipolar residues also led to a degree of hydrogen bond perturbation.
      These effects were most apparent in the solvent exposed exterior of hen egg white
      lysozyme, in which the intraprotein hydrogen bonds tend to be weaker.

PMID- 21186891
TI  - Engineered tissue scaffolds with variational porous architecture.
AB  - This paper presents a novel computer-aided modeling of 3D tissue scaffolds with a
      controlled internal architecture. The complex internal architecture of scaffolds
      is biomimetically modeled with controlled micro-architecture to satisfy different
      and sometimes conflicting functional requirements. A functionally gradient
      porosity function is used to vary the porosity of the designed scaffolds
      spatially to mimic the functionality of tissues or organs. The three-dimensional
      porous structures of the scaffold are geometrically partition into functionally
      uniform porosity regions with a novel offsetting operation technique described in
      this paper. After determining the functionally uniform porous regions, an
      optimized deposition-path planning is presented to generate the variational
      internal porosity architecture with enhanced control of interconnected channel
      networks and continuous filament deposition. The presented methods are
      implemented, and illustrative examples are presented in this paper. Moreover, a
      sample optimized tool path for each example is fabricated layer-by-layer using a
      micronozzle biomaterial deposition system.

PMID- 21186892
TI  - Patient-specific modeling of corneal refractive surgery outcomes and inverse
      estimation of elastic property changes.
AB  - The purpose of this study is to develop a 3D patient-specific finite element
      model (FEM) of the cornea and sclera to compare predicted and in vivo refractive
      outcomes and to estimate the corneal elastic property changes associated with
      each procedure. Both eyes of a patient who underwent laser-assisted in situ
      keratomileusis (LASIK) for myopic astigmatism were modeled. Pre- and
      postoperative Scheimpflug anterior and posterior corneal elevation maps were
      imported into a 3D corneo-scleral FEM with an unrestrained limbus. Preoperative
      corneal hyperelastic properties were chosen to account for meridional anisotropy.
      Inverse FEM was used to determine the undeformed corneal state that produced
      <0.1% error in anterior elevation between simulated and in vivo preoperative
      geometries. Case-specific 3D aspheric ablation profiles were simulated, and
      corneal topography and spherical aberration were compared at clinical intraocular
      pressure. The magnitude of elastic weakening of the residual corneal bed required
      to maximize the agreement with clinical axial power was calculated and compared
      with the changes in ocular response analyzer (ORA) measurements. The models
      produced curvature maps and spherical aberrations equivalent to in vivo
      measurements. For the preoperative property values used in this study, predicted
      elastic weakening with LASIK was as high as 55% for a radially uniform model of
      residual corneal weakening and 65% at the point of maximum ablation in a
      spatially varying model of weakening. Reductions in ORA variables were also
      observed. A patient-specific FEM of corneal refractive surgery is presented,
      which allows the estimation of surgically induced changes in corneal elastic
      properties. Significant elastic weakening after LASIK was required to replicate
      clinical topographic outcomes in this two-eye pilot study.

PMID- 21186893
TI  - Computational fluid dynamics simulations of particle deposition in large-scale,
      multigenerational lung models.
AB  - Computational fluid dynamics (CFD) has emerged as a useful tool for the
      prediction of airflow and particle transport within the human lung airway.
      Several published studies have demonstrated the use of Eulerian finite-volume CFD
      simulations coupled with Lagrangian particle tracking methods to determine local
      and regional particle deposition rates in small subsections of the
      bronchopulmonary tree. However, the simulation of particle transport and
      deposition in large-scale models encompassing more than a few generations is less
      common, due in part to the sheer size and complexity of the human lung airway.
      Highly resolved, fully coupled flowfield solution and particle tracking in the
      entire lung, for example, is currently an intractable problem and will remain so
      for the foreseeable future. This paper adopts a previously reported methodology
      for simulating large-scale regions of the lung airway (Walters, D. K., and Luke,
      W. H., 2010, "A Method for Three-Dimensional Navier-Stokes Simulations of Large
      Scale Regions of the Human Lung Airway," ASME J. Fluids Eng., 132(5), p. 051101),
      which was shown to produce results similar to fully resolved geometries using
      approximate, reduced geometry models. The methodology is extended here to
      particle transport and deposition simulations. Lagrangian particle tracking
      simulations are performed in combination with Eulerian simulations of the airflow
      in an idealized representation of the human lung airway tree. Results using the
      reduced models are compared with those using the fully resolved models for an
      eight-generation region of the conducting zone. The agreement between fully
      resolved and reduced geometry simulations indicates that the new method can
      provide an accurate alternative for large-scale CFD simulations while potentially
      reducing the computational cost of these simulations by several orders of
      magnitude.

PMID- 21186894
TI  - Volumetric stress-strain analysis of optohydrodynamically suspended biological
      cells.
AB  - Ongoing investigations are exploring the biomechanical properties of isolated and
      suspended biological cells in pursuit of understanding single-cell
      mechanobiology. An optical tweezer with minimal applied laser power has
      positioned biologic cells at the geometric center of a microfluidic cross
      junction, creating a novel optohydrodynamic trap. The resulting fluid flow
      environment facilitates unique multiaxial loading of single cells with site
      specific normal and shear stresses resulting in a physical albeit extensional
      state. A recent two-dimensional analysis has explored the cytoskeletal strain
      response due to these fluid-induced stresses [Wilson and Kohles, 2010, "Two
      Dimensional Modeling of Nanomechanical Stresses-Strains in Healthy and Diseased
      Single-Cells During Microfluidic Manipulation," J Nanotechnol Eng Med, 1(2), p.
      021005]. Results described a microfluidic environment having controlled nanometer
      and piconewton resolution. In this present study, computational fluid dynamics
      combined with multiphysics modeling has further characterized the applied fluid
      stress environment and the solid cellular strain response in three dimensions to
      accompany experimental cell stimulation. A volumetric stress-strain analysis was
      applied to representative living cell biomechanical data. The presented normal
      and shear stress surface maps will guide future microfluidic experiments as well
      as provide a framework for characterizing cytoskeletal structure influencing the
      stress to strain response.

PMID- 21186895
TI  - Deformations and end effects in isolated blood vessel testing.
AB  - Blood vessels are commonly studied in isolation to define their mechanical and
      biological properties under controlled conditions. While sections of the wall are
      sometimes tested, vessels are most often attached to needles and examined in
      their natural cylindrical configuration where combinations of internal pressure
      and axial force can be applied to mimic in vivo conditions. Attachments to
      needles, however, constrain natural vessel response, resulting in a complex state
      of deformation that is not easily determined. As a result, measurements are
      usually limited to the midsection of a specimen where end effects do not extend
      and the deformation is homogeneous. To our knowledge, however, the boundaries of
      this uninfluenced midsection region have not been explored. The objective of this
      study was to define the extent of these end effects as a function of vessel
      geometry and material properties, loading conditions, and needle diameter. A
      computational fiber framework was used to model the response of a nonlinear
      anisotropic cylindrical tube, constrained radially at its ends, under conditions
      of axial extension and internal pressure. Individual fiber constitutive response
      was defined using a Fung-type strain energy function. While quantitative results
      depend on specific parameter values, simulations demonstrate that axial stretch
      is always highest near the constraint and reduces to a minimum in the
      uninfluenced midsection region. Circumferential stretch displays the opposite
      behavior. As a general rule, the length of the region disturbed by a needle
      constraint increases with the difference between the diameter of the needle and
      the equilibrium diameter of the blood vessel for the imposed loading conditions.
      The reported findings increase the understanding of specimen deformation in
      isolated vessel experiments, specifically defining considerations important to
      identifying a midsection region appropriate for measurement.

PMID- 21186896
TI  - The effect of kinematic and kinetic changes on meniscal strains during gait.
AB  - The menisci play an important role in load distribution, load bearing, joint
      stability, lubrication, and proprioception. Partial meniscectomy has been shown
      to result in changes in the kinematics and kinetics at the knee during gait that
      can lead to progressive meniscal degeneration. This study examined changes in the
      strains within the menisci associated with kinematic and kinetic changes during
      the gait cycle. The gait changes considered were a 5 deg shift toward external
      rotation of the tibia with respect to the femur and an increased medial-lateral
      load ratio representing an increased adduction moment. A finite element model of
      the knee was developed and tested using a cadaveric specimen. The cadaver was
      placed in positions representing heel-strike and midstance of the normal gait,
      and magnetic resonance images were taken. Comparisons of the model predictions to
      boundaries digitized from images acquired in the loaded states were within the
      errors produced by a 1 pixel shift of either meniscus. The finite element model
      predicted that an increased adduction moment caused increased strains of both the
      anterior and posterior horns of the medial meniscus. The lateral meniscus
      exhibited much lower strains and had minimal changes under the various loading
      conditions. The external tibial rotational change resulted in a 20% decrease in
      the strains in the posterior medial horn and increased strains in the anterior
      medial horn. The results of this study suggest that the shift toward external
      tibial rotation seen clinically after partial medial meniscectomy is not likely
      to cause subsequent degenerative medial meniscal damage, but the consequence of
      this kinematic shift on the pathogenesis of osteoarthritis following meniscectomy
      requires further consideration.

PMID- 21186897
TI  - Axisymmetric optical-trap measurement of red blood cell membrane elasticity.
AB  - The elastic properties of the cell membrane play a crucial role in determining
      the equilibrium shape of the cell, as well as its response to the external forces
      it experiences in its physiological environment. Red blood cells are a favored
      system for studying membrane properties because of their simple structure: a
      lipid bilayer coupled to a membrane cytoskeleton and no cytoplasmic cytoskeleton.
      An optical trap is used to stretch a red blood cell, fixed to a glass surface,
      along its symmetry axis by pulling on a micron-sized latex bead that is bound at
      the center of the exposed cell dimple. The system, at equilibrium, shows Hookean
      behavior with a spring constant of 1.5*10(-6) N/m over a 1-2 MUm range of
      extension. This choice of simple experimental geometry preserves the axial
      symmetry of the native cell throughout the stretch, probes membrane deformations
      in the small-extension regime, and facilitates theoretical analysis. The
      axisymmetry makes the experiment amenable to simulation using a simple model that
      makes no a priori assumption on the relative importance of shear and bending in
      membrane deformations. We use an iterative relaxation algorithm to solve for the
      geometrical configuration of the membrane at mechanical equilibrium for a range
      of applied forces. We obtain estimates for the out-of-plane membrane bending
      modulus B~1*10(-19) Nm and an upper limit to the in-plane shear modulus H<2*10(
      6) N/m. The partial agreement of these results with other published values may
      serve to highlight the dependence of the cell's resistance to deformation on the
      scale and geometry of the deformation.

PMID- 21186898
TI  - Simulation of a chain of collapsible contracting lymphangions with progressive
      valve closure.
AB  - The aim of this investigation was to achieve the first step toward a
      comprehensive model of the lymphatic system. A numerical model has been
      constructed of a lymphatic vessel, consisting of a short series chain of
      contractile segments (lymphangions) and of intersegmental valves. The changing
      diameter of a segment governs the difference between the flows through inlet and
      outlet valves and is itself governed by a balance between transmural pressure and
      passive and active wall properties. The compliance of segments is maximal at
      intermediate diameters and decreases when the segments are subject to greatly
      positive or negative transmural pressure. Fluid flow is the result of time
      varying active contraction causing diameter to reduce and is limited by segmental
      viscous and valvular resistance. The valves effect a smooth transition from low
      forward-flow resistance to high backflow resistance. Contraction occurs
      sequentially in successive lymphangions in the forward-flow direction. The
      behavior of chains of one to five lymphangions was investigated by means of pump
      function curves, with variation of valve opening parameters, maximum
      contractility, lymphangion size gradation, number of lymphangions, and phase
      delay between adjacent lymphangion contractions. The model was reasonably robust
      numerically, with mean flow-rate generally reducing as adverse pressure was
      increased. Sequential contraction was found to be much more efficient than
      synchronized contraction. At the highest adverse pressures, pumping failed by one
      of two mechanisms, depending on parameter settings: either mean leakback flow
      exceeded forward pumping or contraction failed to open the lymphangion outlet
      valve. Maximum pressure and maximum flow-rate were both sensitive to the
      contractile state; maximum pressure was also determined by the number of
      lymphangions in series. Maximum flow-rate was highly sensitive to the transmural
      pressure experienced by the most upstream lymphangions, suggesting that many
      feeding lymphatics would be needed to supply one downstream lymphangion chain
      pumping at optimal transmural pressure.

PMID- 21186899
TI  - Cartilage thickness distribution affects computational model predictions of
      cervical spine facet contact parameters.
AB  - With motion-sparing disk replacement implants gaining popularity as an
      alternative to anterior cervical discectomy and fusion (ACDF) for the treatment
      of certain spinal degenerative disorders, recent laboratory investigations have
      studied the effects of disk replacement and implant design on spinal kinematics
      and kinetics. Particularly relevant to cervical disk replacement implant design
      are any postoperative changes in solid stresses or contact conditions in the
      articular cartilage of the posterior facets, which are hypothesized to lead to
      adjacent-level degeneration. Such changes are commonly investigated using finite
      element methods, but significant simplification of the articular geometry is
      generally employed. The impact of such geometric representations has not been
      thoroughly investigated. In order to assess the effects of different models of
      cartilage geometry on load transfer and contact pressures in the lower cervical
      spine, a finite element model was generated using cadaver-based computed
      tomography imagery. Mesh resolution was varied in order to establish model
      convergence, and cadaveric testing was undertaken to validate model predictions.
      The validated model was altered to include four different geometric
      representations of the articular cartilage. Model predictions indicate that the
      two most common representations of articular cartilage geometry result in
      significant reductions in the predictive accuracy of the models. The two
      anatomically based geometric models exhibited less computational artifact, and
      relatively minor differences between them indicate that contact condition
      predictions of spatially varying thickness models are robust to anatomic
      variations in cartilage thickness and articular curvature. The results of this
      work indicate that finite element modeling efforts in the lower cervical spine
      should include anatomically based and spatially varying articular cartilage
      thickness models. Failure to do so may result in loss of fidelity of model
      predictions relevant to investigations of physiological import.

PMID- 21186900
TI  - The role of mass balance equations in growth mechanics illustrated in surface and
      volume dissolutions.
AB  - Growth mechanics problems require the solution of mass balance equations that
      include supply terms and account for mass exchanges among constituents of a
      mixture. Though growth may often be accompanied by a variety of concomitant
      phenomena that increase modeling complexity, such as solid matrix deformation,
      evolving traction-free configurations, cell division, and active cell
      contraction, it is important to distinguish these accompanying phenomena from the
      fundamental growth process that consists of deposition or removal of mass from
      the solid matrix. Therefore, the objective of this study is to present a
      canonical problem of growth, namely, dissolution of a rigid solid matrix in a
      solvent. This problem illustrates a case of negative growth (loss of mass) of the
      solid in a mixture framework that includes three species, a solid, a solvent, and
      a solute, where the solute is the product of the solid dissolution. By analyzing
      both volumetric and surface dissolutions, the two fundamental modes of growth are
      investigated within the unified framework of mixture theory.

PMID- 21186901
TI  - Intrasac pressure changes and vascular remodeling after endovascular repair of
      abdominal aortic aneurysms: review and biomechanical model simulation.
AB  - In this paper, we review existing clinical research data on post-endovascular
      repair (EVAR) intrasac pressure and relation with abdominal aortic aneurysm (AAA)
      size changes. Based on the review, we hypothesize that intrasac pressure has a
      significant impact on post-EVAR AAA size changes, and post-EVAR remodeling
      depends also on how the pressure has changed over a period of time. The
      previously developed model of an AAA based on a constrained mixture approach is
      extended to include vascular adaptation after EVAR using an idealized geometry.
      Computational simulation shows that the same mechanism of collagen stress
      mediated remodeling in AAA expansion induces the aneurysm wall to shrink in a
      reduced sac-pressure after post-EVAR. Computational simulation suggests that the
      intrasac pressure of 60 mm Hg is a critical value. At this value, the AAA remains
      stable, while values above cause the AAA to expand and values below cause the AAA
      to shrink. There are, however, variations between individuals due to different
      cellular sensitivities in stress-mediated adaptation. Computer simulation also
      indicates that an initial decrease in intrasac pressure helps the AAA shrink even
      if the pressure increases after some time. The presented study suggests that
      biomechanics has a major effect on initial adaptation after EVAR and also
      illustrates the utility of a computational model of vascular growth and
      remodeling in predicting diameter changes during the progression and after the
      treatment of AAAs.

PMID- 21186902
TI  - Pure passive hyperextension of the human cadaver knee generates simultaneous
      bicruciate ligament rupture.
AB  - Knee hyperextension has been described as a mechanism of isolated anterior
      cruciate ligament (ACL) tears, but clinical and experimental studies have
      produced contradictory results for the ligament injuries and the injury sequence
      caused by the hyperextension loading mechanism. The hypothesis of this study was
      that bicruciate ligament injuries would occur as a result of knee hyperextension
      by producing high tibio-femoral (TF) compressive forces that would cause anterior
      translation of the tibia to rupture the ACL, while joint extension would
      simultaneously induce rupture of the posterior cruciate ligament (PCL). Six human
      knees were loaded in hyperextension until gross injury, while bending moments and
      motions were recorded. Pressure sensitive film documented the magnitude and
      location of TF compressive forces. The peak bending moment at failure was 108 N
      m+/-46 N m at a total extension angle of 33.6 deg+/-11 deg. All joints failed by
      simultaneous ACL and PCL damages at the time of a sudden drop in the bending
      moment. High compressive forces were measured in the anterior compartments of the
      knee and likely produced the anterior tibial subluxation, which contributed to
      excessive tension in the ACL. The injury to the PCL at the same time may have
      been due to excessive extension of the joint. These data, and the comparisons
      with previous experimental studies, may help explain the mechanisms of knee
      ligament injury during hyperextension. Knowledge of forces and constraints that
      occur clinically could then help diagnose primary and secondary joint injuries
      following hyperextension of the human knee.

PMID- 21186903
TI  - Biomechanical measurements of torsion-tension coupling in human cadaveric femurs.
AB  - The mechanical behavior of human femurs has been described in the literature with
      regard to torsion and tension but only as independent measurements. However, in
      this study, human femurs were subjected to torsion to determine if a simultaneous
      axial tensile load was generated. Fresh frozen human femurs (n=25) were harvested
      and stripped of soft tissue. Each femur was mounted rigidly in a specially
      designed test jig and remained at a fixed axial length during all experiments.
      Femurs were subjected to external and internal rotation applied at a constant
      angulation rate of 0.1 deg/s to a maximum torque of 12 N m. Applied torque and
      generated axial tension were monitored simultaneously. Outcome measurements were
      extracted from torsion-versus-tension graphs. There was a strong relationship
      between applied torsion and the resulting tension for external rotation tests
      (torsion/tension ratio=551.7+/-283.8 mm, R(2)=0.83+/-0.20, n=25), internal
      rotation tests (torsion/tension ratio=495.3+/-233.1 mm, R(2)=0.87+/-0.17, n=24),
      left femurs (torsion/tension ratio=542.2+/-262.4 mm, R(2)=0.88+/-0.13, n=24), and
      right femurs (torsion/tension ratio=506.7+/-260.0 mm, R(2)=0.82+/-0.22, n=25). No
      statistically significant differences were found for external versus internal
      rotation groups or for left versus right femurs when comparing torsion/tension
      ratios (p=0.85) or R(2) values (p=0.54). A strongly coupled linear relationship
      between torsion and tension for human femurs was exhibited. This suggests an
      interplay between these two factors during activities of daily living and injury
      processes.

PMID- 21186904
TI  - Comparison of MRI-based estimates of articular cartilage contact area in the
      tibiofemoral joint.
AB  - Knee osteoarthritis (OA) detrimentally impacts the lives of millions of older
      Americans through pain and decreased functional ability. Unfortunately, the
      pathomechanics and associated deviations from joint homeostasis that OA patients
      experience are not well understood. Alterations in mechanical stress in the knee
      joint may play an essential role in OA; however, existing literature in this area
      is limited. The purpose of this study was to evaluate the ability of an existing
      magnetic resonance imaging (MRI)-based modeling method to estimate articular
      cartilage contact area in vivo. Imaging data of both knees were collected on a
      single subject with no history of knee pathology at three knee flexion angles.
      Intra-observer reliability and sensitivity studies were also performed to
      determine the role of operator-influenced elements of the data processing on the
      results. The method's articular cartilage contact area estimates were compared
      with existing contact area estimates in the literature. The method demonstrated
      an intra-observer reliability of 0.95 when assessed using Pearson's correlation
      coefficient and was found to be most sensitive to changes in the cartilage
      tracings on the peripheries of the compartment. The articular cartilage contact
      area estimates at full extension were similar to those reported in the
      literature. The relationships between tibiofemoral articular cartilage contact
      area and knee flexion were also qualitatively and quantitatively similar to those
      previously reported. The MRI-based knee modeling method was found to have high
      intra-observer reliability, sensitivity to peripheral articular cartilage
      tracings, and agreeability with previous investigations when using data from a
      single healthy adult. Future studies will implement this modeling method to
      investigate the role that mechanical stress may play in progression of knee OA
      through estimation of articular cartilage contact area.

PMID- 21186905
TI  - Numerical modeling of stress in stenotic arteries with microcalcifications: a
      parameter sensitivity study.
AB  - As a follow-up to the work presented in Wenk et al. (2010, "Numerical Modeling of
      Stress in Stenotic Arteries With Microcalcifications: A Micromechanical
      Approximation," ASME J. Biomech. Eng., 132, p. 091011), a formal sensitivity
      study was conducted in which several model parameters were varied. The previous
      work only simulated a few combinations of the parameters. In the present study,
      the fibrous cap thickness, longitudinal position of the region of
      microcalcifications, and volume fraction of microcalcifications were varied over
      a broader range of values. The goal of the present work is to investigate the
      effects of localized regions of microcalcifications on the stress field of
      atherosclerotic plaque caps in a section of carotid artery. More specifically,
      the variations in the magnitude and location of the maximum circumferential
      stress were assessed for a range of parameters using a global sensitivity
      analysis method known as Sobol' indices. The stress was calculated by performing
      finite element simulations of three-dimensional fluid-structure interaction
      models, while the sensitivity indices were computed using a Monte Carlo scheme.
      The results indicate that cap thickness plays a significant role in the variation
      in the magnitude of the maximum circumferential stress, with the sensitivity to
      volume fraction increasing when the region of microcalcification is located at
      the shoulder. However, the volume fraction played a larger role in the variation
      in the location of the maximum circumferential stress. This matches the finding
      of the previous study (Wenk et al., 2010, "Numerical Modeling of Stress in
      Stenotic Arteries With Microcalcifications: A Micromechanical Approximation,"
      ASME J. Biomech. Eng., 132, p. 091011), which indicates that the maximum
      circumferential stress always shifts to the region of microcalcification.

PMID- 21186906
TI  - Experimental validation of a finite element model of the proximal femur using
      digital image correlation and a composite bone model.
AB  - Computational biomechanical models are useful tools for supporting orthopedic
      implant design and surgical decision making, but because they are a
      simplification of the clinical scenario they must be carefully validated to
      ensure that they are still representative. The goal of this study was to assess
      the validity of the generation process of a structural finite element model of
      the proximal femur employing the digital image correlation (DIC) strain
      measurement technique. A finite element analysis model of the proximal femur
      subjected to gait loading was generated from a CT scan of an analog composite
      femur, and its predicted mechanical behavior was compared with an experimental
      model. Whereas previous studies have employed strain gauging to obtain discreet
      point data for validation, in this study DIC was used for full field quantified
      comparison of the predicted and experimentally measured strains. The strain
      predicted by the computational model was in good agreement with experimental
      measurements, with R(2) correlation values from 0.83 to 0.92 between the
      simulation and the tests. The sensitivity and repeatability of the strain
      measurements were comparable to or better than values reported in the literature
      for other DIC tests on tissue specimens. The experimental-model correlation was
      in the same range as values obtained from strain gauging, but the DIC technique
      produced more detailed, full field data and is potentially easier to use. As
      such, the findings supported the validity of the model generation process, giving
      greater confidence in the model's predictions, and digital image correlation was
      demonstrated as a useful tool for the validation of biomechanical models.

PMID- 21186907
TI  - When learning met memory.
AB  - The first sentence of the introduction to Hebb's (1949) classic monograph, The
      organization of behavior, is "It might be argued that the task of the
      psychologist, the task of understanding behaviour and reducing the vagaries of
      human thought to a mechanical process of cause and effect, is a more difficult
      one than that of any other scientist" (p. xi). Nowhere is this more true than in
      the realm of human learning and memory, given our truly remarkable ability to
      acquire and retain prodigious amounts of information. This article is divided
      into two parts. The first part sketches my lifelong fascination with learning
      that led me to study first memory, then attention, and then their interplay, with
      examples of a few interesting findings along that path. The second part details
      recent work in my laboratory exploring a simple yet quite powerful encoding
      technique: Saying things aloud improves memory for them. This benefit, which we
      call the production effect, likely occurs by enhancing the distinctiveness of the
      things said aloud, and may constitute a beneficial study method. Understanding
      how we learn and remember is ultimately a crucial step in understanding
      ourselves.

PMID- 21186908
TI  - Can "pure" implicit memory be isolated? A test of a single-system model of
      recognition and repetition priming.
AB  - Implicit memory is widely regarded as an unconscious form of memory. However,
      evidence for what is arguably a defining characteristic of implicit memory-that
      its contents are not accessible to awareness-has remained elusive. Such a finding
      of "pure" implicit memory would constitute evidence against a single-system model
      of recognition and priming that predicts that priming will not occur in the
      (true) absence of recognition. In three experiments, using a rapid serial visual
      presentation procedure at encoding, we tested this prediction by attempting to
      replicate some previous studies that claimed to obtain pure implicit memory. We
      found no evidence of priming in the absence of recognition; instead, priming and
      recognition were associated across experiments: when priming was absent,
      recognition was also absent (Experiments 1 and 2), and when priming was reliably
      greater than chance, recognition was similarly greater than chance (Experiment
      3). The results are consistent with the prediction of a single-system model,
      which was fit to the data from all the experiments. The results are also
      consistent with the notion that the memory driving priming is accessible to
      awareness.

PMID- 21186910
TI  - Associative relatedness enhances recall and produces false memories in immediate
      serial recall.
AB  - The influence of permanent lexical network in immediate serial recall is well
      established. The corresponding influence of permanent semantic networks is less
      clear, although such networks are known to both facilitate memory in long-term
      memory tasks and to produce false memories in those same tasks. The current
      experiment involves the study of Deese-Roediger-McDermott (DRM) lists for
      immediate serial recall. The trials in the experiment involved presenting the six
      strongest items from the DRM lists either in intact associatively related lists
      or where those items had been randomly mixed to produce unrelated lists. The
      results of the experiment indicated that the associatively related lists were
      better recalled in order than unrelated lists and the nonpresented critical lure
      was falsely recalled relatively frequently. The results of the experiment confirm
      the importance of associative semantic networks in short-term memory.

PMID- 21186912
TI  - Musing on Brooksian representationalism: a eulogy.
AB  - Lee Brooks was one of the more creative and focused cognitive psychologists of
      his generation. We shared many things, including being of the same generation. We
      differed on many issues but always with respect and affection. This essay
      celebrates his life.

PMID- 21186914
TI  - Effects of age on cross-modal emotion perception.
AB  - Efficient navigation of our social world depends on the generation,
      interpretation, and combination of social signals within different sensory
      systems. However, the influence of healthy adult aging on multisensory
      integration of emotional stimuli remains poorly explored. This article comprises
      2 studies that directly address issues of age differences on cross-modal
      emotional matching and explicit identification. The first study compared 25
      younger adults (19-40 years) and 25 older adults (60-80 years) on their ability
      to match cross-modal congruent and incongruent emotional stimuli. The second
      study looked at performance of 20 younger (19-40) and 20 older adults (60-80) on
      explicit emotion identification when information was presented congruently in
      faces and voices or only in faces or in voices. In Study 1, older adults
      performed as well as younger adults on tasks in which congruent auditory and
      visual emotional information were presented concurrently, but there were age
      related differences in matching incongruent cross-modal information. Results from
      Study 2 indicated that though older adults were impaired at identifying emotions
      from 1 modality (faces or voices alone), they benefited from congruent
      multisensory information as age differences were eliminated. The findings are
      discussed in relation to social, emotional, and cognitive changes with age.

PMID- 21186915
TI  - Older adults' decoding of emotions: role of dynamic versus static cues and age
      related cognitive decline.
AB  - Although age-related deficits in emotion recognition have been widely explored,
      the nature and scope of these deficits remain poorly understood. We conducted two
      experiments to examine whether these deficits are less pronounced when older
      adults evaluate dynamic compared with static images, and second, whether age
      related cognitive decline exacerbates these deficits. Our results suggest that
      age-related cognitive decline exacerbates older adults' deficits in detecting
      anger, but only from static faces. Furthermore, older adults do not show emotion
      recognition deficits when evaluating global emotions from dynamic images of
      faces.

PMID- 21186916
TI  - Is body mass index in old age related to cognitive abilities? The Lothian Birth
      Cohort 1936 Study.
AB  - We tested the hypothesis that the previously reported association between a
      higher body mass index (BMI) and poorer cognition in later adulthood is an
      artifact of confounding by previous cognitive ability and socioeconomic status.
      Participants were 1,079 adults aged about 70 years in the Lothian Birth Cohort
      1936 Study, on whom there are IQ data from age 11. Cognitive outcome measures
      included: IQ at age 70 using the same test that was administered at age 11;
      composite measures of general cognitive ability (g factor), speed of information
      processing, and memory; and two tests of verbal ability. People classified as
      overweight or obese in later adulthood had significantly lower scores on tests of
      childhood IQ, age 70 IQ, g factor, and verbal ability. There was no significant
      association with processing speed or memory performance. After adjusting for
      childhood IQ and social class in general linear models, associations with age 70
      IQ and g factor were nonsignificant or attenuated. However, throughout the
      models, there was a persistent (inverse) relationship between BMI and performance
      on the National Adult Reading Test (NART) and Wechsler Test of Adult Reading
      (WTAR), which remained significant after full adjustment for all sociodemographic
      and health covariates (for the NART, p = .025; for the WTAR, p = .011). The
      findings suggest that the previously reported BMI-cognition associations in later
      adulthood could be largely accounted for by prior ability and socioeconomic
      status, and by the possible influence of these factors on the adoption of health
      behaviors in adulthood.

PMID- 21186918
TI  - The costs of taking it slowly: fast and slow movement timing in older age.
AB  - We investigated adult age-differences in timing control of fast vs. slow
      repetitive movements using a dual-task approach. Twenty-two young (M = 24.23 yr)
      and 22 older adults (M = 66.64 yr) performed three cognitive tasks differing in
      working memory load and response production demands and they tapped series of 550
      ms or 2100-ms target intervals. Single-task timing was comparable in both groups.
      Dual-task timing was characterized by shortening of produced intervals and
      increases in drift and variability. Dual-task costs for both cognitive and timing
      performances were pronounced at slower tapping tempos, an effect exacerbated in
      older adults. Our findings implicate attention and working memory processes as
      critical components of slow movement timing and sources of specific challenges
      thereof for older adults.

PMID- 21186917
TI  - Aging and the vulnerability of speech to dual task demands.
AB  - Tracking a digital pursuit rotor task was used to measure dual task costs of
      language production by young and older adults. Tracking performance by both
      groups was affected by dual task demands: time on target declined and tracking
      error increased as dual task demands increased from the baseline condition to a
      moderately demanding dual task condition to a more demanding dual task condition.
      When dual task demands were moderate, older adults' speech rate declined but
      their fluency, grammatical complexity, and content were unaffected. When the dual
      task was more demanding, older adults' speech, like young adults' speech, became
      highly fragmented, ungrammatical, and incoherent. Vocabulary, working memory,
      processing speed, and inhibition affected vulnerability to dual task costs:
      vocabulary provided some protection for sentence length and grammaticality,
      working memory conferred some protection for grammatical complexity, and
      processing speed provided some protection for speech rate, propositional density,
      coherence, and lexical diversity. Further, vocabulary and working memory capacity
      provided more protection for older adults than for young adults although the
      protective effect of processing speed was somewhat reduced for older adults as
      compared to the young adults.

PMID- 21186919
TI  - Orthographic error monitoring in old age: lexical and sublexical availability
      during perception and production.
AB  - Previous research suggests that older adults suffer declines in producing
      accurate spellings but retain the ability to accurately detect misspellings. The
      preservation of perception in the face of impaired production has been used to
      support a model of aging in which age impairs access to linguistic
      representations under specific circumstances, while representations themselves
      remain intact. The current research tests two predictions of this Transmission
      Deficit Hypothesis (TDH): first, that the differential effect of age on
      perception and production occurs when tasks are equated on response requirements
      and underlying representations, and second, that both word and spelling frequency
      interact to determine the effect of age on performance. Results of two error
      monitoring tasks supported the predictions of the TDH, demonstrating age-related
      production impairments that interacted with both word and spelling frequency, but
      no impairment of older adults' spelling perception, even for low frequency words
      or spellings.

PMID- 21186921
TI  - Silver acetate interactions with nicotine and non-nicotine smoke components.
AB  - Oral topical silver-containing formulations were marketed in the 1970s and 1980s
      as smoking deterrents, based on the finding that when using such formulations, an
      unpleasant taste occurs upon smoking. This approach has not been widely adopted,
      however, in part because of a lack of efficacy data. The advent of new
      pharmacologic treatments for smoking cessation renews the possibility that such a
      taste aversion approach may be a useful adjunct to smoking cessation treatment.
      This study explored the basic mechanistic question of whether topical oral silver
      acetate solution interacts with nicotine as opposed to non-nicotine smoke
      constituents. We recruited 20 smoking volunteers to rate nicotine-containing or
      denicotinized cigarettes, as well as the Nicotrol nicotine vapor inhaler and sham
      (air) puffs. In two sessions, subjects rated the sensory and hedonic qualities of
      puffs after rinsing their mouths with either silver acetate solution or deionized
      water (placebo). Silver acetate relative to placebo solution substantially
      reduced liking and satisfaction ratings for the usual brand and denicotinized
      cigarettes; in contrast, for the nicotine inhaler these ratings were unaffected
      by the silver-based treatment. These results support the conclusion that silver
      acetate not only renders the taste of cigarette smoke less appealing, but also
      that the compound appears to interact selectively with non-nicotine smoke
      constituents. Moreover, these data suggest silver acetate would be compatible
      with buccal nicotine delivery systems (e.g., nicotine lozenge or gum). Combined
      use of taste aversion with nicotine replacement therapy could provide the smoker
      with additional assistance to resist relapse. Further exploration is warranted of
      the use of silver-based preparations as a short-term adjunct to smoking cessation
      treatment.

PMID- 21186920
TI  - Role of progesterone in nicotine addiction: evidence from initiation to relapse.
AB  - Nicotine addiction continues to be the main cause of preventable death in
      developed countries. Women and teen girls appear to be more vulnerable on certain
      aspects of nicotine addiction compared with men and boys. While the mechanism of
      gender differences in nicotine addiction is not yet clear, evidence suggests that
      while estrogen may underlie enhanced vulnerability in females, progesterone may
      protect females. Thus, progesterone may have therapeutic use for tobacco
      addiction, especially in female smokers. A greater understanding of the role of
      progesterone in nicotine addiction is important not only from a treatment
      standpoint, but also from a prevention standpoint: hormone transition phases,
      such as those that occur at adolescence, and during pregnancy and following
      birth, as well as following hormonal manipulation (e.g., using methods of
      hormonal birth control), may all contribute to changes in vulnerability to
      nicotine addiction. In this review, we summarize recent evidence from clinical
      and preclinical studies examining the role of progesterone in nicotine addiction
      focusing on its role during initiation of use and during later phases of the
      addiction process as a potential relapse prevention treatment. We conclude with
      future directions including further examination of progesterone as a potential
      intervention and treatment of nicotine addiction.

PMID- 21186922
TI  - Brain potential indices of novelty processing are associated with preference for
      amphetamine.
AB  - A behavioral drug preference procedure was used to identify two groups of healthy
      individuals. One group preferred 10 mg of d-amphetamine over placebo (Choosers)
      and the other preferred placebo (Nonchoosers). In separate sessions, participants
      were administered placebo, 10, and 15 mg of d-amphetamine, and event-related
      brain potentials (ERPs) were recorded while participants performed two 3-stimulus
      oddball tasks. The effect of d-amphetamine on P3a, an ERP index of the orienting
      response, differed between groups: In Choosers, target stimuli elicited P3a after
      d-amphetamine but not after placebo; in Nonchoosers, the drug had no effect on
      P3a. Moreover, two group differences were evident after placebo and were
      unaffected by d-amphetamine. (1) N100 was larger in Nonchoosers than in Choosers,
      suggesting that Nonchoosers were more attentive than Choosers to the physical
      features of the stimuli. (2) The reorienting negativity (RON) elicited by targets
      in both tasks and by rare nontargets in a novelty oddball task (i.e., novel
      sounds) was larger in Nonchoosers than in Choosers. This suggests that
      Nonchoosers more effectively refocused attention on the task after distraction.
      It is hypothesized that these processing differences reflect a group difference
      in the balance between midbrain dopamine function and ascending cholinergic
      influences. The findings have implications for vulnerability to addiction and
      illustrate the promise of ERPs in parsing elemental phenotypes.

PMID- 21186924
TI  - Phenomenology of adolescent inhalant intoxication.
AB  - Although volatile substance inhalation is prevalent in many contexts and presents
      a serious threat to public health, this pernicious form of substance misuse
      remains poorly understood. The question of why people seek and misuse inhalants
      may be addressed by examining phenomenological accounts of inhalant intoxication,
      yet few investigations of inhalant intoxication experiences are reported in the
      literature. This investigation employed a structured interview to assess inhalant
      intoxication experiences of 267 low-, moderate-, and high-frequency inhalant
      users. Low-frequency inhalant users reported predominately hedonic experiences
      during inhalant intoxication, whereas high-frequency users reported a mixture of
      hedonic and aversive experiences. Aversive experiences such as depressed mood,
      suicidal ideation, and chest pain were commonly reported by high-frequency users
      but were relatively rare among low-frequency users. High-frequency users also
      experienced significantly more euphoria, talkativeness, and grandiosity during
      inhalant intoxication than low-frequency users. Hedonic and aversive experiences
      during episodes of inhalant intoxication are relatively common among high
      frequency adolescent inhalant users.

PMID- 21186923
TI  - The effects of modafinil treatment on neuropsychological and attentional bias
      performance during 7-day inpatient withdrawal from methamphetamine dependence.
AB  - The cognitive benefits of modafinil to patients undergoing 7-day inpatient
      withdrawal from methamphetamine (MA) dependence were examined as part of a double
      blind, randomized, placebo-controlled pilot trial. Recent evidence has identified
      modafinil-related improvements in treatment outcomes for MA-dependent patients;
      however, the benefits to cognition function, which is critical to treatment
      success but known to be impaired, has yet to be examined. The first 20
      participants recruited to the study were administered either 200 mg of modafinil
      (once daily) or placebo, and a neuropsychological test battery (including an MA
      version of the emotional Stroop task) at admission (n = 17) and discharge (n =
      14). Follow-up interviews were conducted at 1-month postdischarge (n = 13). After
      participant withdrawals (3 in each group), treatment was associated with a
      significant improvement in immediate verbal memory recall and nonsignificant
      trend toward improvement on executive function and delayed memory tasks. No
      benefit was seen for measures of verbal learning, visual memory, processing
      speed, or verbal fluency. All participants showed a significant attentional bias
      for MA-related stimuli on the emotional Stroop task. The magnitude of bias
      predicted both retention in treatment and relapse potential at follow-up but was
      not significantly ameliorated by modafinil treatment. While nonsignificant, the
      effect sizes of modafinil-related improvements in executive function and memory
      were consistent with those found in more robustly powered studies of cognitive
      benefits in attention-deficit/hyperactivity disorder and schizophrenia,
      supporting the need for further research.

PMID- 21186925
TI  - Effects of acute caffeine administration on adolescents.
AB  - Acute caffeine administration has physiological, behavioral, and subjective
      effects. Despite its widespread use, few studies have described the impact of
      caffeine consumption in children and adolescents. The purpose of this study was
      to investigate the effects of acute caffeine administration in adolescents. We
      measured cardiovascular responses and snack food intake after acute
      administration of 0 mg, 50 mg, 100 mg, and 200 mg of caffeine. We also compared
      usual food intake and subjective effects of caffeine between high- and low
      caffeine consumers. Finally, we conducted a detailed analysis of caffeine sources
      and consumption levels. We found main effects of caffeine dose on heart rate (HR)
      and diastolic blood pressure (DBP), with HR decreasing and DBP increasing with
      increasing caffeine dose. There were significant interactions among gender,
      caffeine use, and time on DBP. High caffeine consumers (>50 mg/day) reported
      using caffeine to stay awake and drinking coffee, tea, soda, and energy drinks
      more than low consumers (<50 mg/day). Boys were more likely than girls to report
      using getting a rush, more energy, or improved athletic performance from
      caffeine. Finally, when we examined energy and macronutrient intake, we found
      that caffeine consumption was positively associated with laboratory energy
      intake, specifically from high-sugar, low-fat foods and also positively
      associated with protein and fat consumption outside of the laboratory. When taken
      together, these data suggest that acute caffeine administration has a broad range
      of effects in adolescents and that the magnitude of these effects is moderated by
      gender and chronic caffeine consumption.

PMID- 21186926
TI  - Reinforcing efficacy moderates the relationship between impulsivity-related
      traits and alcohol use.
AB  - Studies have shown that impulsivity-related traits are associated with alcohol
      use among college students. It is possible that individual differences in
      susceptibility to reinforcement from alcohol, which reflects the extent to which
      an individual values alcohol, moderates this relationship. Data were collected
      from 255 college students at a large, urban university who reported consuming
      alcohol at least once in the past 30 days. Two impulsivity-related-traits,
      Urgency and Sensation Seeking, were examined, as well as the reinforcing efficacy
      indices of Omax (maximum alcohol expenditure) and Demand Intensity (consumption
      when price = zero). Findings indicated that Omax moderated the relationship
      between both impulsivity-related traits and alcohol consumption, and between
      Urgency and alcohol-related problems. Demand Intensity also moderated the
      relationship between both impulsivity-related traits and alcohol use, but did not
      moderate the relationship between either trait and alcohol-related problems.
      Results from this study suggest that college students high in certain impulsivity
      related traits and for whom alcohol is a highly valued reinforcer have a high
      risk for excessive alcohol consumption and an increased probability of
      experiencing negative alcohol-related problems.

PMID- 21186928
TI  - A comparative study of drug-related attentional bias: evidence from Iran.
AB  - The Addiction-Stroop test has been widely used to investigate the attentional
      correlates of alcohol and drug abuse; however, the majority of the studies have
      been conducted with European and American participants. The present study tested
      whether Iranian drug abusers show higher attentional bias for drug-related
      stimuli. Participants included drug abusers (N = 53; 100% male), with a clinical
      history of opium and heroin abuse, who were in a Methadone Maintenance Therapy
      program. Only nonabusers (N = 71; 71, 54% male) with a history of having never
      abused of drugs or alcohol participated in the study as controls. All
      participants completed a computerized Persian version of classic and addiction
      Stroop tests. The results of a multivariate analysis of covariance (MANCOVA)
      showed that drug abusers had a higher attentional bias for drug-related stimuli
      than nonabusers, after the effects of age and education had been controlled. The
      results of repeating the MANCOVA (a) limited to men only, and (b) to men and
      women in the nonabuser sample showed that the observed difference in the drug
      related attentional bias of drug-abusers and nonabusers was not an artifact of
      gender imbalance. Our findings support the idea that drug-related attentional
      bias is culture-free.

PMID- 21186927
TI  - The Inventory of Gambling Situations in problem and pathological gamblers seeking
      alcohol and drug abuse treatment.
AB  - Identifying situations in which individuals gamble may be important for
      developing or improving treatments, but few instruments exist for examining high
      risk gambling situations. This study evaluated the factor structure of the
      Inventory of Gambling Situations (IGS), an instrument that assesses situations
      that may lead to gambling episodes. Individuals seeking alcohol and drug abuse
      treatment who were identified as problem or pathological gamblers (N = 283)
      completed the IGS, and principal component analysis revealed a 4-factor solution
      best fit the data; the factors represented items related to Negative Affect,
      Positive Affect, Gambling Cues, and Social Situations. Across the whole scale,
      Cronbach's alpha was 0.97, ranging from 0.83 to 0.96 for the four factors. IGS
      total scores correlated with other indices of gambling problems, including number
      of pathological gambling criteria endorsed and frequency and intensity of
      gambling. Race, education, and severity of psychiatric, drug, and alcohol
      problems were significantly predictive of some factor scores. Specifically,
      African Americans were more likely to gamble in response to Negative Affect
      situations than Caucasians, and education was inversely associated with wagering
      in response to Gambling Cues. Psychiatric symptoms were predictive of gambling in
      response to both Positive and Negative Affect situations and Gambling Cues.
      Severity of drug and alcohol problems were related to gambling in Social
      Situations. Results from this study indicate that the IGS has good psychometric
      properties and suggest areas in which intervention efforts may be tailored to
      prevent or treat gambling problems among individuals seeking substance abuse
      treatment.

PMID- 21186929
TI  - Hypothetical intertemporal choice and real economic behavior: delay discounting
      predicts voucher redemptions during contingency-management procedures.
AB  - Delay discounting rates are predictive of drug use status, the likelihood of
      becoming abstinent, and a variety of health behaviors. Rates of delay discounting
      may also be related to other relevant behaviors associated with addiction, such
      as the frequency at which individuals redeem contingency management voucher
      earnings. This study examined the discounting rates of 152 participants in a
      buprenorphine treatment program for opioid abuse. Participants received up to 12
      weeks of buprenorphine treatment combined with contingency management.
      Participant's drug use was measured via urine specimens submitted three times a
      week. Successive negative urine specimens were reinforced with increasing amounts
      of money. After each negative urine specimen, a participant could either redeem
      his or her earnings or accumulate it in an account. Analysis of the frequency of
      redemptions showed that participants with higher rates of delay discounting at
      study intake redeemed their earnings significantly more often than participants
      with lower rates of discounting. Age and income also predicted redemption rates.
      We suggest that delay discounting rates can be used to predict redemption
      behaviors in a contingency management treatment program and that these findings
      are consistent with the recent theory of the competing neurobehavioral decision
      systems.

PMID- 21186930
TI  - Acute effects of a glucose energy drink on behavioral control.
AB  - There has been a dramatic rise in the consumption of glucose energy drinks (e.g.,
      Amp, Monster, and Red Bull) in the past decade, particularly among high school
      and college students. However, little laboratory research has examined the acute
      objective and subjective effects of energy drinks. The purpose of this study was
      to investigate the acute effects of a glucose energy drink (Red Bull) on
      cognitive functioning. Participants (N = 80) were randomly assigned to one of
      five conditions: 1.8 ml/kg energy drink, 3.6 ml/kg energy drink, 5.4 ml/kg energy
      drink, placebo beverage, or no drink. Participants completed a well-validated
      behavioral control task (the cued go/no-go task) and subjective measures of
      stimulation, sedation, and mental fatigue both before and 30 minutes following
      beverage administration. The results indicated that compared with the placebo and
      no drink conditions, the energy drink doses decreased reaction times on the
      behavioral control task, increased subjective ratings of stimulation and
      decreased ratings of mental fatigue. Greatest improvements in reaction times and
      subjective measures were observed with the lowest dose and improvements
      diminished as the dose increased. The findings suggest that energy drink
      consumption can improve cognitive performance on a behavioral control task,
      potentially explaining the dramatic rise in popularity of these controversial new
      beverages.

PMID- 21186931
TI  - Anhedonia associated with stimulant use and dependence in a population-based
      sample of American adults.
AB  - Prior research suggests an association between anhedonia--diminished interest or
      pleasure in rewarding activities--and stimulant use in selected samples. However,
      it is unclear whether this association generalizes to the overall population and
      is consistent across stimulant drug types (amphetamine vs. cocaine) and outcome
      characteristics (any lifetime use vs. dependence). Questions also remain as to
      whether the anhedonia-stimulant relationship is unique from covariance with
      depressed mood, psychiatric disorders, and nonstimulant substance use. The
      current study addressed these questions by examining anhedonia-stimulant
      relationships in a cross-sectional population-based sample of 43,093 American
      adults. Results indicated that lifetime anhedonia and depressed mood each were
      positively associated with lifetime stimulant use and lifetime dependence among
      those who reported stimulant use. Anhedonia-stimulant relationships were
      consistent across amphetamine- and cocaine-related outcomes and distinct from
      covariance with depressed mood, which exhibited no association over and above the
      effect of anhedonia. After adjusting for demographic, psychiatric, and
      nonstimulant substance use characteristics, anhedonia-stimulant associations
      remained significant, although effect sizes were partially attenuated. Lifetime
      anhedonia was also more prevalent among respondents who initiated use but did not
      eventually progress to dependence in comparison with individuals who never once
      used a stimulant drug. Anhedonia appears to be uniquely associated with lifetime
      use of cocaine and amphetamines and lifetime progression from use to dependence
      in the American population. Albeit cross-sectional in nature, these findings add
      further support to the generalizability and specificity of the anhedonia
      stimulant relationship. Future research utilizing longitudinal and experimental
      designs are warranted to clarify the underpinnings of this association.

PMID- 21186932
TI  - Self-subjugation among women: exposure to sexist ideology, self-objectification,
      and the protective function of the need to avoid closure.
AB  - Despite extensive evidence confirming the negative consequences of self
      objectification, direct experimental evidence concerning its environmental
      antecedents is scarce. Incidental exposure to sexist cues was employed in 3
      experiments to investigate its effect on self-objectification variables.
      Consistent with system justification theory, exposure to benevolent and
      complementary forms of sexism, but not hostile or no sexism, increased state self
      objectification, self-surveillance, and body shame among women but not men in
      Experiment 1. In Experiment 2, we replicated these effects and demonstrated that
      they are specific to self-objectification and not due to a more general self
      focus. In addition, following exposure to benevolent sexism only, women planned
      more future behaviors pertaining to appearance management than did men; this
      effect was mediated by self-surveillance and body shame. Experiment 3 revealed
      that the need to avoid closure might afford women some protection against self
      objectification in the context of sexist ideology.

PMID- 21186933
TI  - Dual temperamental risk factors for psychopathic personality: evidence from self
      report and skin conductance.
AB  - Psychopathy is a personality disorder consisting of dysfunctional affective
      interpersonal features (Factor 1) and impulsive-antisocial behavior (Factor 2)
      that exhibit differential associations with palmar skin conductance (SC)
      reactivity. The goal of this study was to determine whether the distinct SC
      reactivity observed in incarcerated psychopaths generalizes to university
      students who score high on personality dimensions hypothesized to be the risk
      factors for these psychopathy factors. Lilienfeld's Psychopathic Personality
      Inventory (PPI; Lilienfeld & Andrews, 1996) was used to compute scores on 2
      factor-analytically derived dimensions that have been the focus of recent
      research in psychopathy. PPI-1 is hypothesized to relate to the low-fear
      temperamental risk factor, whereas PPI-2 is hypothesized to relate to regulatory
      dysfunction. SC reactivity was measured during tasks previously used in studies
      of diagnosed psychopaths. Results indicated that PPI-1 was associated with
      reduced SC during anticipation of an aversive noise and PPI-2 was associated with
      enhanced SC reactivity during presentation of a speech about one's faults.
      Additional analyses explored an 8-factor solution of the PPI and 3 temperament
      dimensions derived from factor analysis of several personality measures.
      Together, the SC results suggest that the Factor 1 pathway, best captured with
      refined assessments of behavioral fearlessness, related to reduced SC reactivity
      to an aversive noise-consistent with a weak defense system. The Factor 2 pathway,
      best captured by higher order dimensions reflecting externalizing, disinhibited
      forms of negative temperament, related to enhanced SC reactivity to a speech
      stressor-consistent with high stress reactivity.

PMID- 21186934
TI  - At the intersection of culture and religion: a cultural analysis of religion's
      implications for secondary control and social affiliation.
AB  - Religion helps people maintain a sense of control, particularly secondary control
      acceptance of and adjustment to difficult situations--and contributes to
      strengthening social relationships in a religious community. However, little is
      known about how culture may influence these effects. The current research
      examined the interaction of culture and religion on secondary control and social
      affiliation, comparing people from individualistic cultures (e.g., European
      Americans), who tend to be more motivated toward personal agency, and people from
      collectivistic cultures (e.g., East Asians), who tend to be more motivated to
      maintain social relationships. In Study 1, an analysis of online church mission
      statements showed that U.S. websites contained more themes of secondary control
      than did Korean websites, whereas Korean websites contained more themes of social
      affiliation than did U.S. websites. Study 2 showed that experimental priming of
      religion led to acts of secondary control for European Americans but not Asian
      Americans. Using daily diary methodology, Study 3 showed that religious coping
      predicted more secondary control for European Americans but not Koreans, and
      religious coping predicted more social affiliation for Koreans and European
      Americans. These findings suggest the importance of understanding sociocultural
      moderators for the effects of religion.

PMID- 21186935
TI  - Desensitization to media violence: links with habitual media violence exposure,
      aggressive cognitions, and aggressive behavior.
AB  - This study examined the links between desensitization to violent media stimuli
      and habitual media violence exposure as a predictor and aggressive cognitions and
      behavior as outcome variables. Two weeks after completing measures of habitual
      media violence exposure, trait aggression, trait arousability, and normative
      beliefs about aggression, undergraduates (N = 303) saw a violent film clip and a
      sad or a funny comparison clip. Skin conductance level (SCL) was measured
      continuously, and ratings of anxious and pleasant arousal were obtained after
      each clip. Following the clips, participants completed a lexical decision task to
      measure accessibility of aggressive cognitions and a competitive reaction time
      task to measure aggressive behavior. Habitual media violence exposure correlated
      negatively with SCL during violent clips and positively with pleasant arousal,
      response times for aggressive words, and trait aggression, but it was unrelated
      to anxious arousal and aggressive responding during the reaction time task. In
      path analyses controlling for trait aggression, normative beliefs, and trait
      arousability, habitual media violence exposure predicted faster accessibility of
      aggressive cognitions, partly mediated by higher pleasant arousal. Unprovoked
      aggression during the reaction time task was predicted by lower anxious arousal.
      Neither habitual media violence usage nor anxious or pleasant arousal predicted
      provoked aggression during the laboratory task, and SCL was unrelated to
      aggressive cognitions and behavior. No relations were found between habitual
      media violence viewing and arousal in response to the sad and funny film clips,
      and arousal in response to the sad and funny clips did not predict aggressive
      cognitions or aggressive behavior on the laboratory task. This suggests that the
      observed desensitization effects are specific to violent content.

PMID- 21186936
TI  - Primary cells and stem cells in drug discovery: emerging tools for high
      throughput screening.
AB  - Many drug discovery screening programs employ immortalized cells, recombinantly
      engineered to express a defined molecular target. Several technologies are now
      emerging that render it feasible to employ more physiologically, and clinically
      relevant, cell phenotypes. Consequently, numerous approaches use primary cells,
      which retain many functions seen in vivo, as well as endogenously expressing the
      target of interest. Furthermore, stem cells, of either embryonic or adult origin,
      as well as those derived from differentiated cells, are now finding a place in
      drug discovery. Collectively, these cells are expanding the utility of authentic
      human cells, either as screening tools or as therapeutics, as well as providing
      cells derived directly from patients. Nonetheless, the growing use of
      phenotypically relevant cells (including primary cells or stem cells) is not
      without technical difficulties, particularly when their envisioned use lies in
      high-throughput screening (HTS) protocols. In particular, the limited
      availability of homogeneous primary or stem cell populations for HTS mandates
      that novel technologies be developed to accelerate their adoption. These
      technologies include detection of responses with very few cells as well as
      protocols to generate cell lines in abundant, homogeneous populations. In
      parallel, the growing use of changes in cell phenotype as the assay readout is
      driving greater use of high-throughput imaging techniques in screening. Taken
      together, the greater availability of novel primary and stem cell phenotypes as
      well as new detection technologies is heralding a new era of cellular screening.
      This convergence offers unique opportunities to identify drug candidates for
      disorders at which few therapeutics are presently available.

PMID- 21186937
TI  - Quantification of hormone sensitive lipase phosphorylation and colocalization
      with lipid droplets in murine 3T3L1 and human subcutaneous adipocytes via
      automated digital microscopy and high-content analysis.
AB  - Lipolysis in adipocytes is associated with phosphorylation of hormone sensitive
      lipase (HSL) and translocation of HSL to lipid droplets. In this study,
      adipocytes were cultured in a high-throughput format (96-well dishes), exposed to
      lipolytic agents, and then fixed and labeled for nuclei, lipid droplets, and HSL
      (or HSL phosphorylated on serine 660 [pHSLser660]). The cells were imaged via
      automated digital fluorescence microscopy, and high-content analysis (HCA)
      methods were used to quantify HSL phosphorylation and the degree to which HSL (or
      pHSLser660) colocalizes with the lipid droplets. HSL:lipid droplet colocalization
      was quantified through use of Pearson's correlation, Mander's M1 Colocalization,
      and the Tanimoto coefficient. For murine 3T3L1 adipocytes, isoproterenol, Lys
      gamma3-melanocyte stimulating hormone, and forskolin elicited the appearance and
      colocalization of pHSLser660, whereas atrial natriuretic peptide (ANP) did not.
      For human subcutaneous adipocytes, isoproterenol, forskolin, and ANP activated
      HSL phosphorylation/colocalization, but Lys-gamma3-melanocyte stimulating hormone
      had little or no effect. Since ANP activates guanosine 3',5'-cyclic monophosphate
      (cGMP)-dependent protein kinase, HSL serine 660 is likely a substrate for cGMP
      dependent protein kinase in human adipocytes. For both adipocyte model systems,
      adipocytes with the greatest lipid content displayed the greatest lipolytic
      responses. The results for pHSLser660 were consistent with release of glycerol by
      the cells, a well-established assay of lipolysis, and the HCA methods yielded Z'
      values >0.50. The results illustrate several key differences between human and
      murine adipocytes and demonstrate advantages of utilizing HCA techniques to study
      lipolysis in cultured adipocytes.

PMID- 21186938
TI  - Symptomatic calcification of a thyroid lobe and surrounding tissue after
      radioactive iodine treatment to ablate the lobe.
AB  - BACKGROUND: Fine-needle aspiration diagnosis of follicular carcinoma presents a
      dilemma because malignancy is confirmed when vascular or capsular invasion is
      present. Completion thyroidectomy may be necessary when the diagnosis of
      follicular carcinoma is made following hemithyroidectomy. Ablation of the
      remaining lobe with radioactive iodine has been used as an alternative to
      completion thyroidectomy. Here we report an unusual apparent complication of this
      treatment. PATIENT FINDINGS: A 51-year-old woman presented in September 24, 2009
      with a stony, hard calcification of left thyroid gland. She complained of recent
      progressive hoarsening of her voice. Her medical history was positive for a
      subtotal thyroidectomy on September 6, 1993. Histologic analysis identified
      follicular carcinoma. Two months postoperatively, the remaining tissue was
      ablated with (131)I (150 mCi) as an alternative to completion thyroidectomy. We
      performed computed tomography of the neck, which demonstrated 1.6  x 1.9 x  2.2
      cm dense speculated calcification of the entire left residual thyroid gland. The
      calcification infiltrated the trachea wall. Completion thyroidectomy, including
      resection of the calcification, was performed. Histologic examination revealed
      dystrophic calcification. CONCLUSION: We report an unusual replacement of the
      thyroid remnant with calcification that developed over a period of 16 years
      following radioactive iodine lobe ablation as an alternative to completion
      thyroidectomy for thyroid follicular carcinoma. To our knowledge, this is the
      first such case in the English language literature.

PMID- 21186940
TI  - Ecosystem engineering impact of Limnoperna fortunei in South America.
AB  - Limnoperna fortunei, or golden mussel, has invaded aquatic ecosystems in the
      Americas following it introduction from Southeast Asia. It is not only an
      aggressive invasive species, it is also a very effective ecosystem engineer,
      altering both ecosystem structure and function, and causes great ecological and
      economic impacts. This paper describes its impact as an ecosystem engineer (on
      benthic communities and the water column). A review of the existing scientific
      literature is presented, and the impact and the mechanisms by which the golden
      mussel modifies, maintains, and creates new environmental conditions in the
      invaded South American inland freshwater environments are analyzed. Understanding
      the ecosystem engineering roles of L. fortunei is important for its management
      and/or control in the invaded areas, and in cases of future invasions.

PMID- 21186941
TI  - Simple procedure for sperm cryopreservation in the larvacean tunicate Oikopleura
      dioica.
AB  - The larvacean tunicate Oikopleura dioica is an attractive organism for studies of
      the development, evolution, and physiology of chordates, showing considerable
      promise for genetic approaches given its short life cycle of five days. To
      facilitate future genetic studies, the development of protocols for the
      maintenance of individual strains is essential. Here we report a simple and
      practical protocol for the cryopreservation of sperm using liquid nitrogen (-196
      degrees C) and dimethyl sulfoxide (DMSO) as a protective agent. The quality of
      the frozen-thawed sperm was evaluated in terms of fertilizing ability and
      subsequent development of the fertilized eggs. We examined several parameters to
      optimize the efficiency of cryopreservation, such as the concentration of DMSO,
      the method for acclimation of sperm to DMSO before freezing, and for placing
      sperm in liquid nitrogen, as well as the pH of the seawater used in resuspending
      the thawed sperm. We confirmed that viable sperm were recovered after
      preservation for more than one year. In addition, mature animals, and even a
      subsequent generation, were obtained from eggs fertilized by the cryopreserved
      sperm. The present procedure seems to be simple and sufficiently practical for
      maintenance of future established lines of O. dioica using frozen sperm.

PMID- 21186939
TI  - Thyroid cancer incidence patterns in the United States by histologic type, 1992
      2006.
AB  - BACKGROUND: The increasing incidence of thyroid cancer in the United States is
      well documented. In this study, we assessed the incidence patterns by histologic
      type according to demographic and tumor characteristics to further our
      understanding of these cancers. METHODS: We used the National Cancer Institute's
      Surveillance, Epidemiology, and End Results (SEER) program for cases diagnosed
      during 1992-2006 to investigate patterns for the four major histologic types of
      thyroid cancer by gender, race/ethnicity, and age as well as registry, tumor
      stage, and size. RESULTS: Among women, papillary thyroid cancer rates were
      highest among Asians (10.96 per 100,000 woman-years) and lowest among blacks
      (4.90 per 100,000 woman-years); follicular cancer rates did not vary
      substantially by race/ethnicity (p-values >0.05), medullary cancer rates were
      highest among Hispanics (0.21 per 100,000 woman-years) and whites (0.22 per
      100,000 woman-years), and anaplastic rates were highest among Hispanics (0.17 per
      100,000 woman-years). Among men, both papillary and follicular thyroid cancer
      rates were highest among whites (3.58 and 0.58 per 100,000 man-years,
      respectively), medullary cancer rates were highest among Hispanics (0.18 per
      100,000 man-years), and anaplastic rates were highest among Asians (0.11 per
      100,000 man-years). Racial/ethnic-specific rates did not vary notably across
      registries. In contrast to age-specific rates of papillary thyroid cancer that
      peaked in midlife (age 50), especially pronounced among women, rates for
      follicular, medullary, and anaplastic types continued to rise across virtually
      the entire age range, especially for anaplastic carcinomas. Female-to-male
      incidence rate ratios among whites decreased with age most steeply for the
      follicular type and least steeply for the medullary type; it was <1 until the
      very oldest ages for the anaplastic type. CONCLUSION: We conclude that the
      similar age-specific patterns and lack of geographical variation across the SEER
      racial/ethnic groups indicate that detection effects cannot completely explain
      the observed thyroid cancer incidence patterns as variation in the amount or
      quality of healthcare provided has been shown to vary by SEER racial/ethnic
      groups, gender, and age. We find that the variations in age-specific patterns by
      gender and across histologic types are intriguing and recommend that future
      etiologic investigation focus on exogenous and endogenous exposures that are
      experienced similarly by racial/ethnic groups, more strongly among women, and
      distinctively by age.

PMID- 21186942
TI  - Taxonomic status of three types of Fejervarya cancrivora from Indonesia and other
      Asian countries based on morphological observations and crossing experiments.
AB  - Although the crab-eating frog Fejervarya cancrivora is one of the most widely
      distributed species in Asian region, taxonomic relationships among different
      populations remain unclarified. In this study, we attempted to elucidate the
      taxonomic status of F. cancrivora from Indonesian and other Asian populations.
      Five populations of F. cancrivora from Selangor (Malaysia), Cianjur (Java,
      Indonesia), Trat (Thailand), Khulna (Bangladesh), and Makassar (Sulawesi,
      Indonesia) were morphologically observed and subjected to crossing experiments.
      Principal component and clustering analyses revealed that these five populations
      could be organized into three groups corresponding to three observed
      morphological types: a Selangor and Cianjur group (large-type), a Trat and Khulna
      group (mangrove-type), and a Makassar group (Sulawesi-type). The limited crossing
      experiments revealed that hybrids between Selangor females and Cianjur and Trat
      males developed normally, whereas hybrids between Selangor females and Khulna
      males showed incomplete gametic isolation. Histological observations of the
      testes of mature males revealed the presence of pycnotic nuclei in the hybrids
      between Selangor females and Khulna males in addition to normal bundles of
      spermatozoa. In contrast, no pycnotic nuclei were observed in the Selangor
      controls. Although meiotic metaphases in the controls were normal, those in
      hybrids showed several abnormalities, such as the appearance of univalents and an
      increase in rod-shaped bivalents. Based on our findings from the morphological
      observations and crossing experiments, we conclude that each of three identified
      types represents a distinct species. We propose that the large-type is F.
      cancrivora, the mangrove-type is F. moodiei, and the Sulawesi-type represents an
      undescribed species.

PMID- 21186943
TI  - Analysis of genetic diversity in earthworms using DNA markers.
AB  - Earthworms are one of the most important and beneficial macrofauna, and are used
      extensively in organic farming. Earthworms mediate soil biological regulation
      systems, and produce biogenic structures. They help to maintain soil structure,
      water infiltration, and regulate the availability of nutrients assimilated by
      plants. The objectives of this study were to perform morphological and molecular
      characterizations of 24 earthworm individuals collected from geographically
      diverse locations to assess the level of genetic variation. For molecular
      analysis, the effectiveness of RAPD, ISSR, and Universal rice primers (URPs)
      markers was investigated to identify polymorphism among 24 isolates of
      earthworms. A total of 62 molecular markers were used for amplification of
      genomic DNA of earthworms. Of these, 10 RAPD, 10 ISSR, and 10 URPs markers were
      used for characterization, which showed 95.7%, 96.7% and 98.3% polymorphism,
      respectively. The dendrogram, generated from the DNA markers by the unweighted
      pair group method using arithmetic averages, grouped all the isolates into two
      main clusters. All Eisenia fetida isolates were clustered in group A, whereas
      group B included three isolates belonging to Eudrilus eugeniae. Molecular markers
      allowed a rapid assessment of genetic variation among these closely related
      isolates of earthworms. These results suggest that molecular markers are a good
      choice for diversity analysis of earthworm individuals.

PMID- 21186944
TI  - Comparison of expression patterns of shell matrix protein genes in the mantle
      tissues between high- and low-quality pearl-producing recipients of the pearl
      oyster, Pinctada fucata.
AB  - The production of a cultured pearl is the result of a complex interplay between
      the donor and recipient oysters. However, there is a paucity of information on
      the relationship between donor and recipient oyster gene expression patterns and
      pearl quality. Shell matrix proteins affect not only the formation of the shell,
      but also that of the pearls. We compared the gene expression patterns of five
      shell matrix proteins (msi60, nacrein, msi31, prismalin-14, and aspein) in the
      mantle edge (ME), which forms the prismatic layer, and the mantle center (MC),
      which forms the nacreous layer, between high- (HP) and low quality pearl- (LP)
      producing recipient oysters. After culturing for about two months, ME and MC
      tissues were collected from nine recipient oysters: four with HP, five with LP.
      In the ME, the average threshold cycle (DeltaC(T)) for aspein was higher in HP
      than in LP (t-test, p = 0.03). Additionally, in the MC, the average DeltaC(T) for
      msi60 was lower in HP than in LP (p = 0.06). This means the relative expression
      level of msi60 in the mantle of HP was higher than that of LP, and expression
      level of aspein in the mantle of HP was lower than that of LP. Pearl quality was
      closely related to the expression patterns of shell matrix protein genes of
      recipient oysters.

PMID- 21186945
TI  - Ultrastructural studies of the formation of the egg capsule in the hermaphroditic
      species, Isohypsibius granulifer granulifer Thulin, 1928 (Eutardigrada:
      Hypsibiidae).
AB  - The egg capsule of Isohypsibius granulifer granulifer Thulin 1928 (Eutardigrada:
      Hypsibiidae) is composed of two shells: the thin vitelline envelope and the
      multilayered chorion. The process of the formation of the egg shell begins in
      middle vitellogenesis. The I. g. granulifer vitelline envelope is of the primary
      type (secreted by the oocyte), but the chorion should be regarded as a mixed
      type: primary (secreted by the oocyte), and secondary (produced by the cells of
      gonad wall). During early choriogenesis, the parts of the chorion are produced
      and then connected into a permanent layer. The completely developed chorion
      consists of three layers: (1) the inner, medium electron dense layer; (2) the
      middle labyrinthine layer; (3) the outer, medium electron dense layer. After the
      formation of the chorion, a vitelline envelope is secreted by the oocyte.

PMID- 21186946
TI  - Light and scanning electron microcopy study of the tongue in Rhea americana.
AB  - Morphological characteristics of the tongue were studied in adult rhea (Rhea
      americana). The lingual surface and the surface of epithelium-connective tissue
      interface of rhea tongue were examined macroscopically and by light and scanning
      electron microscopy. The rhea tongue revealed a triangular aspect, without
      adjustment of the inferior bill formation, occupying approximately 1/4 of the
      length of the oral cavity. Lingual papilla-like structures were not observed over
      the lingual surface. The tongue mucosa was composed of a thick non-keratinized
      stratified squamous epithelium in the dorsal and ventral part, supported by a
      connective tissue core. The submucosa contained numerous glands with cytoplasmic
      granules, and luminal secretion was positive for histochemical reaction to Alcian
      Blue in pH 2.5 and PAS, and negative to Alcian Blue in pH 0.5. Despite the
      rudimentary characteristic of the tongue in rhea, our results suggest an
      important role of tongue secretions in food lubrication and humidification during
      the swallowing process, based on the enormous quantity of lingual glands in the
      submucosa and the histochemical characteristics of their secretions.

PMID- 21186947
TI  - Biogeography and speciation patterns of the golden orb spider genus Nephila
      (Araneae: Nephilidae) in Asia.
AB  - The molecular phylogeny of the globally distributed golden orb spider genus
      Nephila (Nephilidae) was reconstructed to infer its speciation history, with a
      focus on SE Asian/W Pacific species. Five Asian, two Australian, four African,
      and one American species were included in the phylogenetic analyses. Other
      species in Nephilidae, Araneidae, and Tetragnathidae were included to assess
      their relationships with the genus Nephila, and one species from Uloboridae was
      used as the outgroup. Phylogenetic trees were reconstructed from one nuclear
      (18S) and two mitochondrial (COI and 16S) markers. Our molecular phylogeny shows
      that the widely distributed Asian/Australian species, N. pilipes, and an African
      species, N. constricta, form a clade that is sister to all other Nephila species.
      Nested in this Nephila clade are one clade with tropical and
      subtropical/temperate Asian/Australian species, and the other containing African
      and American species. The estimated divergence times suggest that diversification
      events within Nephila occurred during mid-Miocene to Pliocene (16 Mya-2 Mya), and
      these time periods were characterized by cyclic global warming/cooling events.
      According to Dispersal and Vicariance Analysis (DIVA), the ancestral range of the
      Asian/Australian clade was tropical Asia, and the ancestral range of the genus
      Nephila was either tropical Asia or Africa. We conclude that the speciation of
      the Asian/Australian Nephila species was driven by Neogene global cyclic climate
      changes. However, further population level studies comparing diversification
      patterns of sister species are needed to determine the mode of speciation of
      these species.

PMID- 21186948
TI  - A new species of Parapygmephorus Cross, 1965 (Acari; Heterostigmatina;
      Neopygmephoridae) phoretic on Halictus quadricinctus (Fabricius, 1776) (Hym.;
      Halictidae) from Iran.
AB  - A new species of the genus Parapygmephorus Cross, 1965 (Acari: Heterostigmatina,
      Neopygmephoridae) is described from Northeastern Iran. A phoretic adult female of
      Parapygmephorus khorasanicus Hajiqanbar and Khaustov sp. n. was discovered
      clasping on hairs on the ventral body surface of Halictus quadricinctus
      (Fabricius, 1776) (Hymenoptera; Halictidae). It is the fifth representative among
      the known species of the genus Parapygmephorus in the world. Differentiation of
      new species from other species of the genus is discussed, and a key to known
      world species is provided.

PMID- 21186949
TI  - Chromosome differentiation of four 2n = 50 chromosomal forms of Turkish mole rat,
      Nannospalax nehringi.
AB  - Nannospalax is a genus of blind rodents adapted to living in underground. The
      species have numerous chromosomal forms in Turkey, and their taxonomic position
      is still unknown. In this study, 15 mole rats of four different 2n = 50 forms
      were used; C- and G- banding processes were applied; and a comparison was made
      accordingly. Karyological results showed that the 2n = 50S form is a new form for
      Turkish blind mole rats. 2n = 50S form is determined from Andirin (Kahramanmaras)
      and has NF = 70. The 2n = 50W form, on the other hand, differs from the others
      with NF = 74 form. C-banding results showed that heterochromatin blocks of all 2n
      = 50 are different, while only the 2n = 50W form has telomeric heterochromatin
      blocks. G-banding results, however, displayed homologies and differences among
      the chromosomal forms. After comparison, we determined that Robertsonian fusion
      is an efficient force on chromosomal evolution in blind mole rats in Turkey, and
      that telomeric heterochromatin is a distinctive character for the 2n = 50W form.
      We suggest that the chromosomal changing mechanism should be independent from
      climatic peculiarities. These results support the theory that ancestral karyotype
      should have the largest distribution in a chromosomally variable species.

PMID- 21186950
TI  - Megadraconema cornutum, a new genus and species from Korea, with a discussion of
      its classification and relationships within the family Draconematidae (Nematoda,
      Desmodorida) based on morphological and molecular characters.
AB  - A new genus and species of Draconematidae Filipjev, 1918, Megadraconema cornutum
      gen. nov., sp. nov., inhabiting subtidal sediments in Jejudo, Korea is described.
      Megadraconema cornutum gen. nov., sp. nov. is mainly characterized by a long body
      (1630-2220 um), presence of a transverse circle of well-developed papillae-like
      cuticular protrusions at the base of the lip region, a head capsule with
      reticular structure of subcuticle, an amphid with a pore-like opening, and an
      internal, bar-shaped fovea. The diagnosis of the family Draconematidae is emended
      and a key to genus is provided based on their major differential diagnostic
      characteristics, summarized in a table. Phylogenetic relationships of all the
      genera within the Draconematidae are discussed for the first time, based on
      molecular analyses and morphological features. The phylogenetic position of the
      new genus and relationships within the family Draconematidae based on analysis of
      molecular sequence data are examined. Analysis of 18S rRNA gene sequences does
      not support the currently accepted classification, and indicates paraphyly of the
      subfamily Draconematinae.

PMID- 21186951
TI  - Neonatal age and point of careTSH testing in the monitoring of iodine deficiency
      disorders: findings from western Uganda.
AB  - BACKGROUND: Iodine deficiency is a major public health problem throughout Africa.
      Although salt for human consumption is said to contain adequate amounts of iodine
      in Uganda, iodine intake may not be optimal. We undertook a field study to assess
      the adequacy of iodine nutrition in western Uganda using on-site measurement
      methods of neonatal thyroid stimulating hormone (TSH) levels as recommended by
      the World Health Organization (WHO) for monitoring the degree of iodine
      deficiency during pregnancy. METHODS: The study design consisted of a prevalence
      study using the percentage of newborns between the ages of 3 and 7 days with TSH
      >5 mIU/L, measured with a point-of-care immunochromatographic TSH assay, as a
      surrogate marker of iodine deficiency. Five districts in western Uganda were
      selected for study on the basis of a past history of iodine deficiency. One
      thousand seventy-eight newborns from the five districts were sequentially
      enrolled in each separate district and tested between July 2007 and January 2008.
      RESULTS: The prevalence of TSH levels >5 mlU/L ranged from 20% to 32%. Neonates
      tested on or before the age of 3 days were more likely to have a TSH level >5
      mlU/L than those tested beyond the age of three days (28.2% vs. 18.7%, p <
      0.001). CONCLUSIONS: Assessing neonatal TSH levels in developing countries with a
      TSH assay method suitable for field use can be successfully used to screen for
      congenital hypothyroidism and to indirectly assess a population's iodine status.
      Based on the percentage of neonates with TSH values >5 mIU/L, presumptive iodine
      deficiency persists in western Uganda. This finding suggests that continued
      monitoring of iodine nutrition in the area surrounding the Rwenzori Mountains in
      Uganda and Congo is needed. Due to the progressive fall in the percent of TSH
      values >5 mIU/L from day three to day five of life, we conclude that TSH
      measurement earlier than day five of life in newborns at risk for iodine
      deficiency may be misleading. Guidelines for the use of neonatal TSH to monitor
      iodine nutrition should specify that TSH measurement take place no earlier than
      day five of life.

PMID- 21186952
TI  - Multiple endocrine neoplasia type 2B with a RET proto-oncogene A883F mutation
      displays a more indolent form of medullary thyroid carcinoma compared with a RET
      M918T mutation.
AB  - BACKGROUND: Most cases of multiple endocrine neoplasia type 2B (MEN-2B) are
      attributable to a germline methionine to threonine mutation at codon 918 (M918T)
      of the RET proto-oncogene; very few cases of a germline alanine to phenylalanine
      mutation at codon 883 (A883F) are reported without a clear description of the
      clinical course. Nevertheless, RET-A883F is currently considered to be among the
      highest risk mutations, and prophylactic thyroidectomy is recommended as early as
      6 months of life. Further characterization of the clinical behavior of RET-A883F
      mutation is warranted. We present the clinical data for a family with MEN-2B
      associated with RET-A883F mutation. SUMMARY: The proband, a 39-year-old woman,
      had multifocal medullary thyroid carcinoma (MTC) with cervical lymphadenopathy,
      but no evidence of distant metastases. She was disease free after surgical
      resection. She also had bilateral pheochromocytomas and mucosal neuromas leading
      to the clinical diagnosis of MEN-2B. Genetic testing showed that the woman and
      her three children (3-5 years old) had the RET-A883F mutation. The children had
      near-normal calcitonin levels, and none had sonographic evidence of suspicious
      thyroid nodules or cervical lymphadenopathy. CONCLUSION: A family with MEN-2B due
      to RET-A883F mutation displayed a less aggressive form of MTC than what is
      usually seen in patients with RET-M918T mutation. RET-A883F mutation could be a
      lower-risk mutation than previously thought and the current recommendation of
      prophylactic thyroidectomy in the first year of life may not be warranted.
      Further reports will help clarify the natural history of MTC caused by this
      mutation.

PMID- 21186953
TI  - Response to sorafenib at a low dose in patients with radioiodine-refractory
      pulmonary metastases from papillary thyroid carcinoma.
AB  - BACKGROUND: Sorafenib has shown promise in the treatment of patients with
      advanced or metastatic thyroid carcinoma. However, the optimal dose has not been
      established and data on Chinese population are not available. We conducted a
      study to assess the responses to sorafenib at a low dose of 200 mg twice daily in
      patients with progressive radioiodine-refractory pulmonary metastases from
      papillary thyroid carcinoma (PTC). PATIENTS AND METHODS: Eligible patients
      received sorafenib 200 mg orally twice daily. Responses were assessed using
      Response Evaluation Criteria in Solid Tumors and adverse events were assessed
      periodically. The end points included response rate and progression-free
      survival. RESULTS: Nine patients with radioiodine-refractory PTC were enrolled in
      the study and treated for a minimum of 13 weeks. The objective partial response
      rate was 33%. The stable disease rate was 44%. The mean progression-free survival
      was 42 weeks (95% confidence interval, 29.5 to 53.9). Two patients showed disease
      progression, and one of them died at 4 months after beginning of treatment. There
      was a marked and rapid change in the serum thyroglobulin level after start of
      treatment, with a mean decrease of 60% within 12 weeks, consistent with
      radiographic findings. Although the types of toxicities were consistent with
      other sorafenib trials, their severity was relatively mild. None of the patients
      discontinued sorafenib or reduced their dose because of treatment-related adverse
      events. CONCLUSION: Sorafenib at a dose of 200 mg twice daily has a potential
      therapeutic effect and is well tolerated in Chinese patients with PTC and
      radioiodine-refractory pulmonary metastases. Further study is warranted with a
      larger cohort of patients.

PMID- 21186954
TI  - Hashimoto's thyroiditis affects symptom load and quality of life unrelated to
      hypothyroidism: a prospective case-control study in women undergoing
      thyroidectomy for benign goiter.
AB  - BACKGROUND: Hashimoto's thyroiditis (HT) is a common disease, and is the most
      prevalent cause of hypothyroidism. Symptoms and diseases associated with HT are
      considered to be caused by hypothyroidism. We hypothesized that higher
      antithyroperoxidase (anti-TPO) antibody levels would be associated with an
      increased symptom load and a decreased quality of life in a female euthyroid
      patient collective. METHODS: In a prospective cohort study 426 consecutive
      euthyroid female patients undergoing thyroid surgery for benign thyroid disease
      were included. Main outcome measures were preoperative anti-TPO levels, a symptom
      questionnaire and the SF-36 questionnaire, and lymphocytic infiltration of the
      thyroid tissue as evaluated by histology. RESULTS: Histology revealed HT in
      28/426 (6.6%) subjects. To maximize the sum of the predictive values, a cut-off
      point for anti-TPO of 121.0 IU/mL was calculated (sensitivity 93.3% [95%
      confidence interval: 77.9%-99.0%]; specificity 94.7% [95% confidence interval:
      92.0%-96.7%]) to predict the presence of histological signs of HT. The mean
      number of reported symptoms was significantly higher in patients with anti-TPO
      levels >121.0 IU/mL than in the other group (6.7 +/- 2.5 vs. 4.1 +/- 2.8; p <
      0.001). There were no differences in preoperative thyroid-stimulating hormone
      levels (1.7 +/- 1.3 vs. 1.5 +/- 1.4 MUU/mL, respectively; p = 0.155). Chronic
      fatigue, dry hair, chronic irritability, chronic nervousness, a history of breast
      cancer and early miscarriage, and lower quality-of-life levels were significantly
      associated with anti-TPO levels exceeding the cut-off point (p < 0.05).
      CONCLUSIONS: Women with HT suffer from a high symptom load. Hypothyroidism is
      only a contributing factor to the development of associated conditions.

PMID- 21186955
TI  - A family with congenital hypothyroidism caused by a combination of loss-of
      function mutations in the thyrotropin receptor and adenylate cyclase-stimulating
      G alpha-protein subunit genes.
AB  - BACKGROUND: Resistance to thyrotropin (TSH) causes congenital hypothyroidism
      (CH). TSH receptor (TSHR) and adenylate cyclase-stimulating G alpha protein
      subunit (GNAS) loss-of-function mutations cause TSH resistance. We describe a
      family with TSH resistance and CH bearing a combination of inactivating mutations
      in TSHR and GNAS genes. We describe studies to determine the molecular mechanisms
      involved in TSH resistance in this family. METHODS: DNA sequencing to identify
      TSHR and GNAS gene mutations was performed. In vitro effects of the mutations on
      cAMP production and TSH binding were investigated in COS7 cells. cAMP production
      was evaluated by transfecting a cAMP response element (CRE)-luciferase reporter
      with pSVL-TSHR and pSVK3-GNAS vectors. For binding studies, cells transfected
      with pSVL-TSHR vectors were incubated with iodine-125 bovine TSH ((125)IbTSH).
      RESULTS: Family members with and without CH were heterozygous for the TSHR mutant
      p.E34K or the GNAS mutant c.750_751insA (=GNASMut). The propositus had CH and he
      was heterozygous for TSHR p.E34K; his mother, also heterozygous for TSHR p.E34K,
      did not have CH. The euthyroid propositus' wife was heterozygous for GNASMut. The
      propositus' two daughters had CH, one was heterozygous for GNASMut and the other
      a compound heterezygous for TSHR p.E34K and GNASMut. Albright's hereditary
      osteodystrophy phenotype was present in those with GNASMut mutation but only the
      daughters had pseudohypoparathyroidism type 1a. Cells transfected with TSHRE34K
      had lower TSH affinity and less CRE-luciferase response than cells transfected
      with TSHR wild-type (WT). Cells transfected with GNASMut did not stimulate CRE
      luciferase activity, but when cells were transfected with GNASMut plus GNASWT, a
      similar response to GNASWT alone was observed. The combination of TSHRWT and
      GNASWT showed higher CRE-luciferase response than TSHRWT and TSHRE34K with either
      GNASWT or GNASWT plus GNASMut. CONCLUSIONS: CH was caused by loss-of-function
      mutations in TSHR and/or GNAS. The absence of CH in the propositus' mother argues
      against a role for TSHR p.E34K being the only cause of CH. The minimal thyroidal
      phenotypic differences between the sisters with pseudohypoparathyroidism type 1a
      and TSH resistance, both heterozygous for GNAS c.750_751insA but only one bearing
      the TSHR p.E34K mutant, suggest that the main cause for CH was preferential
      expression of the mutated maternal GNAS allele in the thyroid gland.

PMID- 21186958
TI  - Characterization of stem cells from alveolar periodontal ligament.
AB  - Complete and predicable regeneration of complex periodontal structures, which
      include cementum, periodontal ligament (PDL), and alveolar bone, has been a great
      challenge for periodontal researchers. It is generally believed that human PDL
      from the root surface contains stem cells (r-PDLSCs), which can enhance
      cementum/PDL-like tissues regeneration in vivo. In this work, PDL was found to
      possess asymmetrically distributed stem cells observed by long-term
      bromodeoxyuridine (BrdU) labeling. Putative stem cells from human PDL on the
      alveolar bone surface (a-PDLSCs) were then isolated and characterized. It was
      shown that a-PDLSCs exhibited strong proliferation capability and expressed high
      percentages of mesenchymal stem cell markers. Comparatively, a-PDLSCs had higher
      multilineage differentiation potential than r-PDLSCs with regard to both
      osteogenic and adipogenic differentiation. Alkaline phosphatase activity and the
      expression of mineralization-related markers of a-PDLSCs were also higher than
      those of r-PDLSCs. In vivo, a-PDLSCs could regenerate bone/PDL-like structures
      and repair critical-size defects created in calvarial bone of NOD/SCID mice.
      Autologous PDLSC-mediated periodontal regeneration showed that a-PDLSCs could
      accomplish reconstruction of alveolar bone more perfectly than r-PDLSCs. Our data
      suggest that PDLSCs may have quite different characteristics depending on
      locations. a-PDLSCs may take a synergistic effect with r-PDLSCs in periodontal
      regeneration.

PMID- 21186957
TI  - Prophylactic antibiotic days as a predictor of sensitivity patterns in
      Acinetobacter pneumonia.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) secondary to Acinetobacter spp.
      in critically ill trauma patients has increased. More importantly, the incidence
      of multi-drug-resistant (MDR) Acinetobacter VAP has increased. The risk factors
      for this increase in resistance have yet to be elucidated. The purpose of this
      study was to evaluate the change in Acinetobacter sensitivity over time and
      determine which risk factors predict resistance in trauma patients. METHODS:
      Patients surviving >5 days post-injury who had Acinetobacter VAP (>=10(5) colony
      forming units/mL in bronchoalveolar lavage fluid) who were seen over five years
      were divided according to pathogen sensitivity (sensitive [SEN] vs. MDR) and
      stratified by age, severity of shock (base excess, number of blood transfusions),
      injury severity (Injury Severity Score [ISS], admission Glasgow Coma Scale [GCS]
      score, chest and extremity Abbreviated Injury Scale score [AIS]), and year.
      Prophylactic (Pro), empiric (Emp), Pro + Emp, and total antibiotic days,
      ventilator days, and mortality rate were compared. Multivariable logistic
      regression (MLR) was performed to determine which risk factors were independent
      predictors of resistance. RESULTS: Ninety-six patients (81% male) were
      identified: 62 SEN and 34 MDR. The groups were clinically similar in terms of
      age, extent of shock, and injury severity with the exception of extremity AIS.
      Antibiotic exposure was greater in the MDR group. Over the period of the study,
      the incidence of MDR Acinetobacter VAP increased from zero to 66% (p < 0.0001).
      Multiple logistic regression identified Pro antibiotic days as an independent
      predictor of MDR after adjusting for age and chest AIS (p < 0.0001). CONCLUSIONS:
      The incidence of MDR Acinetobacter VAP has increased over time. More severe
      extremity injuries, as measured by the AIS, may contribute to prolonged
      antibiotic exposure in those patients with MDR Acinetobacter VAP. Multiple
      logistic regression identified Pro antibiotic days as an independent risk factor
      for MDR Acinetobacter VAP in trauma patients.

PMID- 21186959
TI  - Evidence-based techniques to assess the performance of dental implants.
AB  - The clinical use of evidence-based medicine has been regarded as one of the most
      significant medical advancements of the last century. As the costs of medical
      care escalate, clinical decisions have to be made prudently and with a high
      degree of efficacy. One of the most expensive treatments in dentistry includes
      the use of dental implants to rehabilitate partial and fully edentulous patients.
      Due to the high costs of treatments and the ever increasing varieties of dental
      implants becoming available, the clinician is often faced with a challenging
      situation to decide the best prostheses for their patients. Furthermore,
      navigating through the vast database of literature pertaining to dental implants
      and their related research can be very time consuming and challenging to a dental
      surgeon before they can make appropriate clinical decisions. Similar to other
      orthopedic implants, dental implants need to be evaluated for their long-term
      efficacy in vivo before they are clinically acceptable. In order to help
      clinician(s) make patient oriented decisions, evidence-based techniques are
      becoming increasingly popular. This can be a very useful tool in translating
      research findings into clinical practice, thus narrowing the gap between research
      and clinical dentistry. This article discusses ways in which evidence-based
      techniques can help dental surgeons analyze and make informed clinical decisions
      about dental implant treatments. 

PMID- 21186960
TI  - Oral rehabilitation of severe dentoalveolar trauma: a clinical report.
AB  - This clinical report describes the oral rehabilitation of an adult male who
      suffered severe dentoalveolar trauma as a result of a motor vehicle accident. The
      specific objectives of this treatment were to restore esthetics and masticatory
      function. Treatment included removal of fractured roots, placement of multiple
      endosseous implants, and placement of anterior and posterior metal-ceramic crowns
      and fixed partial dentures. Three year clinical examination revealed no pathology
      associated with the rehabilitation. The patient's esthetic and functional
      expectations were successfully achieved.

PMID- 21186961
TI  - The all-on-four immediate function treatment concept with NobelActive implants: a
      retrospective study.
AB  - The All-on-Four treatment concept provides patients with an immediately loaded
      fixed prosthesis supported by 4 implants. This single-center retrospective study
      evaluated the concept while using the NobelActive implant (Nobel Biocare,
      Gothenburg, Sweden). Seven hundred eight implants placed in 165 subjects
      demonstrated a cumulative survival rate of 99.6% (99.3% in maxilla and 100% in
      the mandible) for up to 29 months of loading. The definitive prosthesis survival
      rate was 100%.

PMID- 21186962
TI  - Fixed rehabilitation of severely atrophic jaws using immediately loaded basal
      disk implants after in situ bone activation.
AB  - Rehabilitation of severely atrophic jaws is facilitated when basal disk implants
      are used after activation of the future bony implant bed with a purpose-designed
      instrument (Osteotensor) 45 to 90 days before implant surgery. Fabrication of a
      highly rigid, screw-secured fixed prosthesis that acts as an external orthopedic
      fixator permits immediate functional loading. This protocol also represents a
      second chance for patients who have experienced complete implant loss and/or bone
      graft failure.

PMID- 21186964
TI  - Sertraline treatment of children and adolescents with posttraumatic stress
      disorder: a double-blind, placebo-controlled trial.
AB  - OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of
      sertraline in children and adolescents who met Diagnostic and Statistical Manual
      of Mental Disorders, 4th edition (DSM-IV) criteria for posttraumatic stress
      disorder (PTSD). METHOD: Children and adolescents (6-17 years old) meeting DSM-IV
      criteria for PTSD were randomized to 10 weeks of double-blind treatment with
      sertraline (50-200  mg/day) or placebo. The primary efficacy measure was the
      University of California, Los Angeles Post-Traumatic Stress Disorder Index for
      DSM-IV (UCLA PTSD-I). RESULTS: A total of 131 patients met entry criteria and
      were randomized to sertraline (n = 67; female, 59.7%; mean age, 10.8; mean UCLA
      PTSD-I score, 43.8 +/- 8.5) or placebo (n = 62; female, 61.3%; mean age, 11.2;
      mean UCLA PTSD-I score, 42.1 +/- 8.8). There was no difference between sertraline
      and placebo in least squares (LS) mean change in the UCLA PTSD-I score, either on
      a completer analysis (-20.4 +/- 2.1 vs. -22.8 +/- 2.1; p = 0.373) or on an last
      observation carried forward (LOCF) end point analysis (-17.7 +/- 1.9 vs. -20.8 +/
      2.1; p = 0.201). Attrition was higher on sertraline (29.9%) compared to placebo
      (17.7%). Discontinuation due to adverse events occurred in a 7.5% treated with
      sertraline and 3.2% treated with placebo. CONCLUSIONS: Sertraline was a generally
      safe treatment in children and adolescents with PTSD, but did not demonstrate
      efficacy when compared to placebo during 10 weeks of treatment.
      ClinicalTrials.gov Identifier: NCT00150306.

PMID- 21186965
TI  - Risperidone-induced weight gain in referred children with autism spectrum
      disorders is associated with a common polymorphism in the 5-hydroxytryptamine 2C
      receptor gene.
AB  - Weight gain is an important adverse effect of risperidone, but predictors of
      significant weight gain have yet to be identified in pediatric patients. Here, we
      investigated differences between age- and gender-normed body mass index
      standardized z scores at baseline and after 8 weeks of open-label, flexible-dose
      risperidone treatment (mean dose: 1.70  mg/day) in 32 youths with pervasive
      developmental disorder (mean age = 8.74, range = 5-16 years) in relation to 
      759C/T 5-hydroxytryptamine 2C receptor (HTR2C) promoter and rs1414334 HTR2C
      intragenic C/G alleles, along with gender, age, and risperidone dose, using
      repeated measures analyses of variance. Carriers of the HTR2C promoter T allele
      gained an average of 0.043 +/- 0.017 body mass index-standardized z scores (1.84
      +/- 1.51  kg) versus 0.64 +/- 0.35 z (3.23 +/- 1.47  kg) for non-T-allele
      carriers (p < 0.001). Presence of the rs1414334 C allele played no significant
      role. Further, weight gain appeared to be associated with younger age and higher
      doses of risperidone. The current preliminary findings suggest that the variant T
      allele of the -759C/T HTR2C promoter polymorphism is protective against
      risperidone-induced weight gain. Younger children and those treated with higher
      doses of risperidone may be at higher risk for weight gain.

PMID- 21186966
TI  - Age-dependent metabolic effects of second-generation antipsychotics in second
      generation antipsychotic-naive French Canadian patients.
AB  - BACKGROUND: Patients receiving second-generation antipsychotics (SGAs) may
      experience secondary metabolic effects such as weight gain, as well as changes in
      lipid and glucose metabolism. These effects are well documented in adults;
      however, fewer studies are available concerning their occurrence and their
      evolution in children and adolescents. OBJECTIVE: The aim of this study was to
      determine if there is an age-dependent variation in the metabolic effects of SGAs
      in a drug-naive population. METHODS: Charts of 232 French Canadian patients
      participating in a program monitoring the metabolic effects of SGAs were
      retrospectively reviewed. A total of 85 SGA-naive patients were selected,
      including 58 youths and 27 adults. Changes, relative to baseline, in weight, body
      mass index, lipid metabolism (total cholesterol, low-density lipoprotein, high
      density lipoprotein, and triglyceride), and fasting blood glucose were assessed,
      with follow-up at 3, 6, 12, and 24 months. RESULTS: With respect to weight gain,
      in both the youth and adult groups, body mass index significantly increased from
      baseline at 3 months (10.1% [p < 0.0001] and 12.2% [p < 0.0001], respectively)
      and 6 months (11.8% [p < 0.0001] and 13.1% [p < 0.0001], respectively). With
      respect to lipid metabolism, in the youth group, there was no significant change.
      In the adult group, there was a significant increase at 3 and 6 months in total
      cholesterol (24.0% [p = 0.004] and 24.1% [p = 0.0006], respectively), low-density
      lipoprotein (26.8% [p = 0.019] and 30.1% [p = 0.010], respectively), and high
      density lipoprotein (10.2% [p = 0.04] and 17.1% [p = 0.005], respectively). There
      was no significant change in triglyceride and glucose metabolism in both groups.
      CONCLUSIONS: Our results confirm the age-independent effects of SGA on weight
      gain. However, more data are needed to explore the age effect on glucose and
      lipid metabolism.

PMID- 21186967
TI  - Some effects of risperidone and quetiapine on growth parameters and hormone
      levels in young pigtail macaques.
AB  - OBJECTIVE: Atypical antipsychotic drugs are prescribed to young children for a
      number of symptoms, some with no Food and Drug Administration approval for
      children. Effects on growth of children have received little experimental study.
      We assessed the effects of two atypicals, risperidone and quetiapine, on growth,
      prolactin, and thyroid hormones of young pigtail macaques (macaca nemestrina),
      modeling potential effects on 4-8-year-old children. METHODS: Subjects were
      studied blindly after random assignment to risperidone (N = 10), quetiapine (N =
      10), or placebo (N = 20). Four phases were studied: (1) predrug, 9-12 months of
      age; (2) low dose (risperidone 0.025  mg/kg, quetiapine 2  mg/kg), 13-16 months;
      (3) high dose (risperidone 0.05  mg/kg, quetiapine 4  mg/kg), 17-20 months; (4)
      postdrug, 21-24 months. Body weight was measured daily, skeletal dimension
      monthly, and bone mineralization and hormones bimonthly. RESULTS: Our primary
      result showed that, compared with placebo, neither drug had detrimental effects
      on body weight, skeletal dimensions, or thyroid hormones. However, in a transient
      effect, bone density was lower following low-dose risperidone than either
      quetiapine or placebo. In both drug phases, risperidone prolactin was higher than
      the other groups, which did not differ. The higher prolactin of the risperidone
      group may partially explain the bone density effect. CONCLUSION: This 16-month
      study of young, developing pigtail macaques given risperidone at doses from 0.025
      to 0.05  mg/kg or quetiapine at doses from 2 to 4  mg/kg suggests that these
      drugs are safe for normal body weight and skeletal growth in young pigtail
      macaques given an adequate diet, although these drugs are known to cause
      significant weight gain and other metabolic changes in some children,
      adolescents, and adult humans. In addition, the results, although transient in
      our study, also suggest that research in children on bone mineralization effects
      of risperidone, and possibly other antipsychotic drugs, may be warranted.

PMID- 21186968
TI  - Serum ferritin and amphetamine response in youth with attention
      deficit/hyperactivity disorder.
AB  - INTRODUCTION: Iron deficiency (ID) has been associated with attention and
      behavioral problems, in general, and with attention-deficit/hyperactivity
      disorder (ADHD), in particular. The study aim was to explore whether iron stores,
      as reflected by serum ferritin concentration, predicted response to
      psychostimulants. METHODS: Six- to 14-year-old children with ADHD enrolled in a
      multiphase, double-blind, randomized, placebo-controlled trial investigating zinc
      supplementation in treating ADHD and optimizing response to psychostimulants. The
      Swanson, Nolan, and Pelham (SNAP) ADHD rating scale was the primary clinical
      instrument. Serum ferritin concentration was obtained at baseline and 8 weeks
      later. Partial correlations, adjusting for age and sex, were computed. RESULTS:
      Fifty-two participants (83% males) had a mean age of 10 years. Their ADHD
      symptoms were moderately severe at baseline (SNAP item mean = 2.1). Their mean
      ferritin concentration was 18.4  ng/mL, with 23% of the participants having a
      level below 7, the assay-defined threshold for ID. Serum ferritin was inversely
      correlated with baseline inattention, hyperactivity/impulsivity, and total ADHD
      symptom scores (Partial Spearman's r = -0.31, p = 0.04; r = -0.42, p < 0.006; and
      r = -0.43, p < 0.004, respectively) and with the weight-adjusted dose of
      amphetamine used to optimize clinical response (Partial Spearman's r = -0.45, p <
      0.007). Psychotropic-treatment history moderated some, but not all, of these
      associations, with previously medicated children showing a stronger association
      between ferritin concentration and ADHD symptom severity. CONCLUSION: These
      findings add to the growing literature implicating ID in ADHD. The prediction of
      amphetamine optimal dose by ferritin concentration suggests that iron
      supplementation should be investigated as a potential intervention to optimize
      response to psychostimulants at a lower dose in individuals with low iron stores
      and ADHD.

PMID- 21186970
TI  - Psychometric properties of the Children's Depression Rating Scale-Revised in
      adolescents.
AB  - OBJECTIVE: The aim of this study was to present the reliability and validity of
      the Children's Depression Rating Scale-Revised (CDRS-R) in the adolescent age
      group. METHOD: Adolescents with symptoms of depression were assessed using the
      CDRS-R and global severity and functioning scales at screening, baseline, and
      after 12 weeks of fluoxetine treatment. Global improvement was also assessed at
      week 12 (or exit). Reliability and validity were analyzed using Classical Test
      Theory (item-total correlations and internal consistency) and correlations
      between the CDRS-R and other outcomes. RESULTS: Adolescents (n = 145) were
      evaluated at screening; 113 (77.9%) met criteria for major depressive disorder, 8
      (5.5%) had subthreshold depressive symptoms, and 24 (16.6%) had minimal
      depressive symptoms. Ninety-four adolescents had a baseline visit after 1 week,
      and 88 were treated with fluoxetine. Internal consistency for the CDRS-R was good
      at all three visits (screening: 0.79; baseline: 0.74; exit: 0.92), and total
      score was highly correlated with global severity (r = 0.87, 0.80, and 0.93; p <
      0.01). Only exit CDRS-R score was significantly correlated with global
      functioning (Children's Global Assessment Scale; r = -0.77; p < 0.01). Reductions
      on the CDRS-R total score were highly correlated with improvement scores at exit
      (Clinical Global Impressions-Improvement; r = -0.83; p < 0.01). CONCLUSIONS: The
      results demonstrate good reliability and validity in adolescents with depression.

PMID- 21186969
TI  - Executive function deficits in children with attention-deficit/hyperactivity
      disorder and improvement with lisdexamfetamine dimesylate in an open-label study.
AB  - OBJECTIVE: To assess the effects of lisdexamfetamine dimesylate (LDX) on
      executive function (EF) behaviors in children with attention
      deficit/hyperactivity disorder (ADHD). METHODS: This observational, open-label, 7
      week, dose-optimization study of LDX (20-70  mg/day) in children with ADHD
      evaluated efficacy with the ADHD Rating Scale IV; safety measures included
      adverse events (AEs). EF was assessed with the Behavior Rating Inventory of
      Executive Function (BRIEF). Post hoc analyses examined BRIEF scores by sex, ADHD
      subtype, comorbid psychiatric symptoms, and common treatment-emergent AEs
      (TEAEs). ADHD Rating Scale IV scores were assessed in subjects categorized by
      baseline BRIEF global executive composite T scores with clinically significant
      (>=65) or not clinically significant (<65) impairment in EF. RESULTS: Mean
      (standard deviation) change from baseline to endpoint for BRIEF of -17.9 (12.5)
      for Global Executive Composite, -15.4 (12.6) for Behavioral Regulation Index, and
      -17.6 (12.3) for Metacognition Index demonstrated improvement with LDX (pooled
      doses; p < 0.0001 for all). Improvements in BRIEF scores were seen regardless of
      sex, ADHD subtype, comorbid psychiatric symptoms, common TEAEs, or baseline EF
      impairment category. TEAEs included decreased appetite, decreased weight,
      irritability, insomnia, headache, upper abdominal pain, and initial insomnia.
      CONCLUSIONS: Improvements were demonstrated in EF behaviors and ADHD symptoms
      with LDX. LDX safety profile was consistent with long-acting stimulant use.

PMID- 21186971
TI  - Safety and efficacy of rivastigmine in adolescents with Down syndrome: long-term
      follow-up.
AB  - Following the completion of a 20-week, open-label study of the safety and
      efficacy of liquid rivastigmine for adolescents with Down syndrome, 5 of the 10
      adolescents in the clinical trial continued long-term rivastigmine therapy and 5
      did not. After an average period of 38 months, all 10 subjects returned for a
      follow-up assessment to determine the safety and efficacy of long-term
      rivastigmine use. Rivastigmine was well tolerated and overall health appeared to
      be unaffected by long-term rivastigmine use. Performance change on cognitive and
      language measures administered at the termination of the open-label clinical
      trial was compared between the two groups. No between-group difference in median
      performance change across the long-term period was found, suggesting that the
      long-term use of rivastigmine does not improve cognitive and language
      performance. However, two subjects demonstrated remarkable improvement in
      adaptive function over the long-term period. Both subjects had received long-term
      rivastigmine therapy. The discussion addresses the challenge of assessing
      cognitive change in clinical trials using adolescents with Down syndrome as
      subjects and the use of group versus individual data to evaluate the relevance of
      medication effects.

PMID- 21186972
TI  - The importance of taking a history of over-the-counter medication use: a brief
      review and case illustration of "PRN" antihistamine dependence in a hospitalized
      adolescent.
AB  - Over-the-counter (OTC) and prescription medication abuse has been rapidly
      increasing, yet publications on OTC abuse in adolescents are limited. We present
      a brief literature review and a novel report of antihistamine dependence emerging
      after admission in an adolescent, subsequently treated with naltrexone. This case
      highlights the need to take a thorough history of OTC, herbal, and prescription
      drug use from parents and patients separately and repeatedly, at initial
      presentation, and again if withdrawal symptoms emerge. General strategies for
      combating OTC and prescription abuse are given.

PMID- 21186975
TI  - Adolescent with treatment-refractory schizophrenia and clozapine-induced
      cardiomyopathy managed with high-dose olanzapine.

PMID- 21186976
TI  - Buprenorphine-induced elevated liver enzymes in an adolescent patient.

PMID- 21186977
TI  - Effect of honey on 50% complement hemolytic activity in infants with protein
      energy malnutrition: a randomized controlled pilot study.
AB  - Protein energy malnutrition (PEM) is associated with a significant impairment of
      cell-mediated immunity and complement system, which may be responsible for the
      high incidence of infections among these patients. This study was designed to
      examine the effect of honey, as a natural substance, on the 50% complement
      hemolytic activity (CH50) in patients with PEM. Thirty patients with PEM and 20
      healthy infants serving as controls participated in this study. The patients were
      randomized to receive either honey (group 1) or placebo (group 2), in addition to
      conventional nutritional rehabilitation therapy. Measurements of weight, midarm
      circumference, skin fold thickness, serum albumin, and CH50 were done for all
      patients before and after 2 weeks of rehabilitation. Before nutritional
      rehabilitation, the CH50 was significantly lower in the PEM groups compared with
      the control. However, after rehabilitation, the CH50 increased significantly in
      both PEM groups, compared with the pre-interventional state and with the
      controls. Moreover, the rise of CH50 was significantly more in the honey group
      compared with the placebo. On the other hand, the improvement in the
      anthropometric measures and serum albumin did not differ significantly between
      the honey and placebo groups after rehabilitation. Thus honey supplementation in
      patients with PEM increased the level of CH50. Whether this would have an effect
      on the frequency and severity of infections in patients with PEM needs further
      studies.

PMID- 21186979
TI  - Erratum.

PMID- 21186981
TI  - The World of Edward Hartley Angle, MD, DDS.

PMID- 21186982
TI  - Anti-acetylcholinesterase and antioxidant assets of the major components
      (salicin, amentoflavone, and chlorogenic acid) and the extracts of Viburnum
      opulus and Viburnum lantana and their total phenol and flavonoid contents.
AB  - Some Viburnum species are used for preparation of the traditional drink called
      gilaburu in Anatolia. In the current study, our goal was to evaluate
      acetylcholinesterase (AChE) inhibitory and antioxidant activities of the ethyl
      acetate, methanol, and water extracts prepared from the branches, leaves, and
      fruits of Viburnum opulus and Viburnum lantana along with salicin, amentoflavone,
      and chlorogenic acid, three major compounds abundantly found in these species.
      AChE enzyme inhibition was tested in vitro using an enzyme-linked immunosorbent
      assay microplate reader at 50, 100, and 200 MUL/mL concentrations. Antioxidant
      activity was examined by ferrous ion chelating capacity, ferric reducing
      antioxidant power, and beta-carotene bleaching assay at 500, 1,000, and 2,000
      MUg/mL. Total phenol and flavonoid contents of the extracts were also established
      by Folin-Ciocalteau and AlCl(3) reagents, respectively. Our data revealed that
      the leaf methanol extract of V. opulus displayed a significantly high inhibitory
      effect against AChE (57.63 +/- 1.23%, 87.41 +/- 0.99%, and 93.19 +/- 0.87% at 50,
      100, and 200 MUg/mL, respectively). The extracts of V. lantana exerted higher
      antioxidant activity.

PMID- 21186983
TI  - Biological properties of (1 -> 3)-beta-D-glucan-based synthetic oligosaccharides.
AB  - Despite the fact that beta-glucans are well-established immunomodulators, the
      problems with batch-to-batch heterogeneity remains problematic. The aim of this
      study was to prepare and evaluate new type of synthetic oligosaccharides. A new
      family of oligo-(1 -> 3)-beta-d-glucans modified on the reducing end was
      synthesized using a controlled and specific inversion of configuration at C-2
      starting from already formed oligo-(1 -> 3)-beta-d-glucans. The designed
      glycosides are characterized by the presence of four or five glucopyranose
      entities and a mannose residue at the reducing end. To study of the impact of
      well-defined structural modulations, we used murine and human models to evaluate
      their immunostimulating potential. These novel oligosaccharides showed strong and
      long-lasting stimulation of phagocytosis and significant potentiation of
      synthesis and/or secretion of interleukin (IL-2, IL-4, IL-5, IL-6), tumor
      necrosis factor-alpha, and vascular endothelial growth factor. In addition, the
      oligosaccharides tested showed significant effects on expression of several genes
      in human fibroblasts and breast cancer cells. From our results it is clear that
      these synthetic oligosaccharides represent a better alternative to natural beta
      glucans.

PMID- 21186984
TI  - Kefir improves the efficacy and tolerability of triple therapy in eradicating
      Helicobacter pylori.
AB  - Preliminary evidence has suggested that probiotics may improve eradication rates
      in patients infected with Helicobacter pylori treated by triple therapy. This
      study examined the effect of combining triple therapy with kefir, a fermented
      milk drink containing probiotics. A randomized, double-blind study was carried
      out on 82 consecutive patients with symptoms of dyspepsia and H. pylori infection
      confirmed by the urea breath test. Patients were given a two times a day, 14-day
      course of lansoprazole (30 mg), amoxicillin (1,000 mg), and clarithromycin (500
      mg) with either 250 mL of kefir twice daily (triple therapy + kefir, n = 46) or
      250 mL of milk containing placebo (triple therapy + placebo, n = 36). Side
      effects were determined using a standard questionnaire form at 15 days after
      beginning treatment. Patients returned for urea breath tests 45 days after
      beginning treatment. Significantly more triple therapy + kefir patients achieved
      eradication (36 of 46 [78.2%]) compared with triple therapy + placebo patients
      (18 of 36 [50.0%]) (P = .026, chi(2) test). Side effects were significantly less
      frequent and less severe in triple therapy + kefir patients than in triple
      therapy + placebo patients. We conclude that a 14-day regimen of triple therapy
      with kefir is more effective in achieving H. pylori eradication than is triple
      therapy alone.

PMID- 21186985
TI  - Treatment of ovarian cancer cells with nutlin-3 and resveratrol combination leads
      to apoptosis via caspase activation.
AB  - The current study was focused on the induction of apoptotic effects of
      resveratrol along with the combination treatments of nutlin-3 and transforming
      growth factor-beta (TGF-beta) against the human ovarian cancer cell line
      A2780/CP70. To determine the extent of apoptosis following the above-mentioned
      treatments, we assessed the execution of apoptotic events that proceed via
      caspase activation and cytochrome c release. We estimated the caspase-3 and -9
      activities using a direct enzymatic assay that measures the cleavage of synthetic
      peptide substrate (N-acetyl-Asp-Glu-Val-Asp-p-nitroanilide). Our experiments
      showed an increase in caspase-3 and -9 activities in the cells that were treated
      with the combination of resveratrol (5 MUM) with nutlin-3 (5 MUM) or TGF-beta (1
      MUg/mL). Since activation of procaspase-3 by caspase-9 requires the release of
      cytochrome c into the cytoplasm, we measured the levels of cytochrome c in the
      cytoplasm by western blot experiments. The data indicated a considerable increase
      in caspase-3 and cytochrome c levels when cells were treated with drugs for 24
      hours. Experiments with 4,6'-diamino-2-phenylindole dihydrochloride (DAPI)
      staining also confirmed the induction of apoptosis in all the above-mentioned
      treatments done at 24 and 48 hours. These results support our hypothesis that
      resveratrol combination can induce programmed cell death at doses that are less
      than half of what is typically needed for nutlin-3 and TGF-beta to induce
      apoptosis.

PMID- 21186988
TI  - Evaluation methods in telehealth: getting to outcomes-a physician's insight.
      Interview by Jamie Devereaux.

PMID- 21186986
TI  - Modulation of leptin levels by oxidized linoleic acid: a connection to
      atherosclerosis?
AB  - The objective of the study was to determine the effects of oxidized linoleic acid
      (Ox-LA) on plasma leptin and to determine the relationship between plasma leptin
      levels and atherosclerosis in animals treated with Ox-LA. Low-density lipoprotein
      (LDL) receptor knockout (LDL r(-/-)) mice were fed a high fat diet with or
      without Ox-LA for 11 weeks. Plasma leptin levels in the high fat group consuming
      Ox-LA were significantly higher (14,052 +/- 601 pg/mL vs. 10,950 +/- 541 pg/mL; P
      < .01) compared to the group receiving the high fat diet alone. There was a
      highly significant correlation between the plasma leptin levels and aortic
      atherosclerotic lesions. From this we conclude that chronic exposure to dietary
      Ox-LA increases the plasma levels of leptin in LDL r(-/-) mice on a high fat
      diet. Considering our previous finding that dietary Ox-LA increased
      atherosclerosis, the current findings emphasize the need to reduce dietary intake
      of oxidized fat.

PMID- 21186989
TI  - New frontiers: telehealth innovations of 2010.

PMID- 21186990
TI  - A business model analysis of telecardiology service.
AB  - Telecare has become an increasingly common medical service in recent years.
      However, new service must be close to the market and be market-driven to have a
      high likelihood of success. This article analyzes the business model of a
      telecardiology service managed by a general hospital. The methodology of the
      article is as follows: (1) initially it describes the elements of the service
      based on the ontology of the business model, (2) then it transfers these elements
      into the choices for business model dynamic loops and examines their validity,
      and (3) finally provides an empirical financial analysis of the service to assess
      the profit-making possibilities.

PMID- 21186991
TI  - Practice guidelines for videoconferencing-based telemental health - October 2009.

PMID- 21186992
TI  - ATA Institutional Council.

PMID- 21186993
TI  - Reviews on trichinellosis (II): neurological involvement.
AB  - Neurological involvement may occur in 0.2%-52% of cases with trichinellosis,
      generally in the most severely affected patients. This review focuses on
      neurotrichinellosis and includes a brief overview of selected cases reported in
      the literature. Our primary goal was to increase the awareness of infectious
      diseases specialists, neurologists, and general practitioners about these major
      complications with possible fatal outcome. Seventy seven of the cases, for which
      enough details were available, have been pooled for statistical analysis. The
      mean age of the investigated group was 34.6 +/- 16.8 years. Patients with both
      focal and diffuse manifestations predominated (55.8%), and they were
      significantly older (40 +/- 15.5 years old) than those who presented solely focal
      (28.9 +/- 17.8 years old; p = 0.03) or diffuse lesions (27.9 +/- 15.3 years old;
      p = 0.007). In most of the cases (59.7%), complete recovery was reported, whereas
      23.4% of cases had sequelae and 16.9% of the patients died. Patients who died had
      significantly lower eosinophil counts (13.8% +/- 14%) when compared with those
      who made complete recovery (28.7% +/- 18%; p = 0.015) and the cases with sequelae
      (35% +/- 17.9%; p = 0.006). To sum up, trichinellosis must be considered in the
      differential diagnosis of any patient with encephalitis or other central nervous
      system malady of ambiguous etiology.

PMID- 21186994
TI  - Laboratory practices for the identification of Shiga toxin-producing Escherichia
      coli in the United States, FoodNet sites, 2007.
AB  - Clinical laboratory practices affect patient care and disease surveillance. It is
      recommended that laboratories routinely use both culture for Escherichia coli
      O157 and a method that detects Shiga toxins (Stx) to identify all Stx-producing
      E. coli (STEC) and that labs send broths or isolates to a public health
      laboratory. In 2007, we surveyed laboratories serving Foodborne Diseases Active
      Surveillance Network sites that performed on-site enteric disease diagnostic
      testing to determine their culture and nonculture-based testing practices for
      STEC identification. Our goals were to measure changes over time in laboratory
      practices and to compare reported practices with published recommendations.
      Overall, 89% of laboratories used only culture-based methods, 7% used only Stx
      enzyme immunoassay (EIA), and 4% used both Stx EIA and culture-based methods.
      Only 2% of laboratories reported simultaneous culture for O157 STEC and use of
      Stx EIA. The proportion that ever used Stx EIA increased from 6% in 2003 to 11%
      in 2007. The proportion that routinely tested all specimens with at least one
      method was 66% in 2003 versus 71% in 2007. Reference laboratories were less
      likely than others to test all specimens routinely by one or more of these
      methods (48% vs. 73%, p=0.03). As of 2007, most laboratories complied with
      recommendations for O157 STEC testing by culture but not with recommendations for
      detection of non-O157 STEC. The proportion of laboratories that culture stools
      for O157 STEC has changed little since 2003, whereas testing for Stx has
      increased.

PMID- 21186995
TI  - Association of methylene tetrahydrofolate reductase C677T genotype with type 2
      diabetes mellitus patients with and without renal complications.
AB  - Diabetes is gradually getting the status of a global epidemic, with India
      projected as the capital of type 2 diabetes mellitus (T2DM). Nephropathy is an
      important complication of diabetes and a major cause of end-stage renal disease.
      Studies from different parts of the world have given controversial results
      regarding the association of methylene tetrahydrofolate reductase (MTHFR) gene
      variation with T2DM and diabetic nephropathy (DN). This case-control study
      assessed the association of MTHFR C677T mutation in T2DM and DN cases. Genotyping
      of MTHFR was carried out for 236 T2DM cases with diabetes diagnosed for >8 years,
      having either normoalbuminuria (n=100) or established DN (n=136). One hundred age
      and sex-matched healthy individuals with normal blood sugars and no family
      history of T2DM were selected as controls. This first report from India gives a
      highly significant odds ratio of 4.0423 (95% confidence interval=1.8753-8.7133),
      indicating that the MTHFR 677T allele confers a fourfold risk of developing DM in
      our population. The frequency of the T allele in both the DM and DN groups was
      similar (i.e., 0.16 and 0.11, respectively), showing no association with the
      initiation or progression of DN. Individuals with a family history of diabetes or
      with risk factors such as obesity, hypertension, and impaired glucose tolerance
      should be screened for MTHFR C677T mutation and may be prescribed folic acid,
      vitamin B6, and vitamin B12 to assess if this helps in delaying the onset of
      diabetes.

PMID- 21186996
TI  - Identification of the COL2A1 mutation in patients with type I Stickler syndrome
      using RNA from freshly isolated peripheral white blood cells.
AB  - Stickler syndrome type I is caused by mutations in the type II collagen gene
      (COL2A1), which is specifically expressed in cartilage and vitreous humor. We
      developed a simple and noninvasive strategy for identifying the COL2A1 mutation
      using RNA from freshly isolated peripheral white blood cells and identified a new
      3' splice site mutation in a Japanese family with Stickler syndrome. RNA was
      isolated from a patient's peripheral white blood cells that had been incubated
      with cycloheximide, an inhibitor of nonsense-mediated mRNA decay. COL2A1 cDNA
      fragments covering the entire coding region were obtained by RT-polymerase chain
      reaction cloning using a high-fidelity DNA polymerase and sequenced. Whole
      sequencing of the patient's cDNA resulted in identification of a 49-bp deletion
      in the region corresponding to exon 18. The deletion introduced a premature
      termination codon. Targeted genome sequencing identified a base substitution at
      the A (-2) position of the 3' splice acceptor site of intron 17. This mutation
      led to utilization of the cryptic splice site, which is located 49 bases
      downstream of the normal splice site and causes aberrant mRNA splicing, resulting
      in a 49-base deletion in the patient's mRNA. Our method is much easier than
      conventional genomic screening and provides a simple and noninvasive diagnostic
      test for patients with Stickler syndrome.

PMID- 21186997
TI  - Epidermal growth factor +61 G/A polymorphism and the risk of hepatocellular
      carcinoma in a Chinese population.
AB  - BACKGROUND: Chronic hepatitis B virus (HBV) infection is a risk factor of
      hepatocellular carcinoma (HCC) in China. Epidermal growth factor (EGF) plays an
      important role in tumorigenesis. The association between EGF +61 G/A polymorphism
      and the risk of HCC is still controversial and ambiguous. AIM: The objective of
      this study was to investigate the association between EGF +61 G/A polymorphism
      and the risk of HCC in a Chinese population. METHODS: A hospital-based case
      control study was designed in a Chinese population. EGF +61 G/A polymorphisms
      were determined in 120 chronic HBV-infected HCC patients, 120 chronic HBV
      infected cirrhotic patients, and 120 healthy controls. The genotype frequency of
      this polymorphism was determined by using a polymerase chain reaction-restriction
      fragment length polymorphism assay. RESULTS: EGF +61 GG (odds ratio=2.76, 95%
      confidence interval=1.03, 7.38; p=0.04) and G allele frequencies (odds
      ratio=1.59, 95% confidence interval=1.08, 2.34; p=0.02) in the HCC group were
      higher than those in the cirrhosis group. EGF +61 A and G allele frequencies in
      healthy subjects were 28.8% and 71.2%. No relationship between EGF +61 G/A gene
      polymorphism and HCC risk was found among our recruited HCC patients and healthy
      controls. CONCLUSION: This study suggests that EGF +61 GG genotype is associated
      with a higher risk of chronic HBV-infected HCC in the Chinese population.

PMID- 21186998
TI  - A versatile adeno-associated virus vector producer cell line method for scalable
      vector production of different serotypes.
AB  - Application of adeno-associated virus (AAV) vector in large animal studies and
      clinical trials often requires high-titer and high-potency vectors. A number of
      currently used vector production methods, based on either transient transfection
      or helper virus infection of cell lines, have their advantages and limitations.
      We previously developed a 293-cell-based producer cell line method for high-titer
      and high-potency AAV2 vectors. Similar to several other methods, however, it
      requires multiple cloning steps for the vector and packaging plasmids and a two
      step transfection and selection for stable cell lines. Here we report a
      simplified method with several key improvements and advantages: (1) a one-step
      cloning of AAV vector cassette into the serotype-specific packaging plasmid; (2)
      a single plasmid transfection and selection for stable AAV vector producer cell
      lines; (3) high vector yields of different serotypes, e.g., AAV2, 8, and 9, upon
      infection with an E1A/E1B-deleted helper adenovirus; (4) efficient packaging of
      both single-stranded and double-stranded (self-complementary) AAV vectors; and
      (5) efficient packaging of large AAV cassettes such as a mini-dystrophin vector
      (5.0 kb). All cell lines were stable with growth rates identical to the parental
      293 cells. The vector yields were consistent among serotypes, with 5 * 10(13) to
      8 * 10(13) vector genome particles per Nunc cell factory (equivalent to 40 15-cm
      plates). The vectors showed high potency for in vitro and in vivo transduction.
      In conclusion, the simple and versatile AAV producer cell line method can be
      useful for large scale AAV vector production in preclinical and clinical studies.

PMID- 21186999
TI  - Stromal-derived factor-1/CXCR4 signaling: indispensable role in homing and
      engraftment of hematopoietic stem cells in bone marrow.
AB  - Homing and engraftment of hematopoietic stem/progenitor cells (HSPCs) in bone
      marrow is the major determining factor in success of hematopoietic stem cell
      transplantation. This is a complex, multistep process orchestrated by the
      coordinated interplay between adhesion molecules, cytokines, growth factors, and
      regulatory cofactors, many of which remain to be defined. Recent studies have
      highlighted the pivotal role of unique stromal-derived factor-1 (SDF-1)/CXCR4
      signaling in the regulation of HSPC homing and subsequent engraftment. In
      addition, studies suggest that SDF-1/CXCR4 signaling acts as an essential
      survival-promoting factor of transplanted HSPCs as well as maintenance of
      quiescent HSCs in bone marrow niche. These pleiotropic effects exerted by SDF
      1/CXCR4 axis make this unique signaling initiator very promising, not only for
      optimal hematopoietic reconstitution but also for the development of innovative
      approaches to achieve restoration, regeneration, or repair of other damaged
      tissues potentially amendable to reversal by stem cell transplantation. This goal
      can only be achieved when the role of SDF-1/CXCR4 axis in hematopoietic
      transplantation is clearly defined. Hence, this review presents current knowledge
      of the mechanisms through which SDF-1/CXCR4 signaling promotes restoration of
      hematopoiesis by regulating the homing and engraftment of HSPCs.

PMID- 21187000
TI  - Stem cell therapy for digestive tract diseases: current state and future
      perspectives.
AB  - Diseases of the digestive tract are complex and encompass a broad spectrum of
      different pathogeneses (inflammatory, ischemic, neoplastic, and functional
      deficit). The digestive tract is not a sterile environment, and its organs are
      composed of tissues with different embryologic origin and different morphologic
      and functional complexity. As a consequence, the management of these diseases is
      often challenging. Stem cell (SC) therapy has yielded some promising results in
      preclinical studies, and, recently, some approaches have been tested clinically.
      Indeed, during the last 5 years, the number of clinical trials with SCs for
      treatment of digestive tract diseases has increased 10-fold. The most advanced
      programs involve liver failure, Crohn's disease, and fistulous disease and are
      now in phase III of development. If progress continues and the preliminary
      results are confirmed, SC therapy will become a clinical reality in the near
      future. In this review we examine the basic concepts of the SC therapy, analyze
      the potential benefits of SCs in diseases of the digestive tract, and summarize
      current experience in the field and the future perspectives.

PMID- 21187001
TI  - Human mesenchymal stem cells cultured with salivary gland biopsies adopt an
      epithelial phenotype.
AB  - Sjogren's syndrome and radiotherapy for head and neck cancer result in severe
      xerostomia and irreversible salivary gland damage for which no effective
      treatment is currently available. Cell culture methods of primary human salivary
      gland epithelial cells (huSGs) are slow and cannot provide a sufficient number of
      cells. In addition, the majority of cultured huSGs are of a ductal phenotype and
      thus not fluid/saliva secretory cells. Some reports indicated that mesenchymal
      stem cells (MSCs) possessed the potential to differentiate into epithelial cells.
      To test this hypothesis with huSGs, a coculture system containing 2 chambers
      separated by a polyester membrane was used to study the capacity of human MSCs to
      adopt an epithelial phenotype when cocultured with human salivary gland biopsies.
      Results were that 20%-40% of cocultured MSCs expressed tight junction proteins
      [claudin-1 (CLDN-1), -2, -3, and -4; occludin; junctional adhesion molecule-A;
      and zonula occludens-1] as well as other epithelial markers [aquaporin-5, alpha
      amylase (alpha-AMY), and E-cadherin], and generated a higher transepithelial
      electrical resistance. Electron microscopy demonstrated that these MSCs had
      comparable cellular structures to huSGs, such as tight junction structures and
      numerous secretory granules. Quantitative real time (RT)-polymerase chain
      reaction revealed an upregulation of several salivary genes (aquaporin-5, AMY,
      and CLDN-2). Moreover, the amounts of alpha-AMY detected in cocultured MSCs were
      comparable to those detected in huSGs control cultures. These data suggest that
      cocultured MSCs can demonstrate a temporary change into a salivary gland acinar
      phenotype.

PMID- 21187002
TI  - Construct validation of the Language Independent Functional Evaluation versus the
      Barthel Index in a Mongolian community.
AB  - PURPOSE: Differences in language and literacy impede our understanding of the
      impact of disability around the world. Since function is primarily action, the
      computer-animated Language Independent Functional Evaluation (L.I.F.E.) might
      bypass the use of written or verbal scales. This study validates L.I.F.E. in a
      developing world population. METHODS: Families were randomly chosen from the city
      centre, suburban 'ger' districts and countryside of Arvaikheer, Mongolia. The
      L.I.F.E. and cross-translated Mongolian Barthel Index were administered in random
      order. Demographics including subjective observation of disability were gathered.
      L.I.F.E. scores were converted to Barthel equivalents. RESULTS: One hundred forty
      four persons completed the test, 24 answered for other persons. Persons with
      observed disability had lower L.I.F.E. scores (64.55 vs. 94.53, p < 0.001).
      L.I.F.E. and Barthel scores related well. (Spearman's rho = 0.757, p < 0.001; for
      persons with observed disability Pearson r = 0.820, p < 0.001). Individual
      functions all had high interclass correlations (>0.75), except bowel and bladder,
      which had moderate correlations. Qualitative inquiry found the L.I.F.E. was
      preferred over the Barthel. CONCLUSIONS: Using L.I.F.E., function can be measured
      without language or literacy. L.I.F.E. expands our ability to measure and compare
      the prevalence of disability and the impact of rehabilitation across regions
      perhaps leading to more rational allocation of resources.

PMID- 21187003
TI  - Computational assessment of the environmental fate, bioaccumulation, and toxicity
      potential of brominated benzylpolystyrene.
AB  - Brominated benzylpolystyrene (BrBPS) is a fire safety polymer, which imparts
      flame retardancy in a variety of styrenic polymers and resins. In this study, the
      individual components of BrBPS were evaluated using a novel screening process to
      inform various endpoints relevant for assessing risks to the environment and
      human health. For this purpose, representative components were created using the
      B3LYP density functional method to generate the energetically optimal bromine
      substitution patterns of the parent molecules toluene, ethylbenzene, and cumene.
      Representative low energy conformations of the components were identified by
      using repetitive short bursts of Molecular Dynamics, followed by Molecular
      Mechanics minimization. The resulting structures were energy minimized at the
      quantum mechanical Becke-Perdew GGA density functional level. Thereafter,
      octanol:water partition coefficients, maximum molecular lengths, average maximum
      diameters, and cross-sectional diameters were calculated to inform parameters on
      environmental fate, bioaccumulation, and mammalian and ecological toxicity. The
      relevance of these data for informing risk assessment is discussed.

PMID- 21187005
TI  - Retroperitoneal cryptococcoma in a case of disseminated cryptococcosis on
      antifungal maintenance therapy.
AB  - Cryptococcoma is a rare entity, characterized by solid, space-occupying masses,
      usually found in the brain. It has been reported in the setting of "paradoxical"
      immune reconstitution inflammatory syndrome. A case of retroperitoneal
      cryptococcoma in a HIV-infected woman with a clinical history of disseminated
      cryptococcosis on antifungal maintenance therapy is described.

PMID- 21187004
TI  - Developing vasculature and stroma in engineered human myocardium.
AB  - We recently developed a scaffold-free patch of human myocardium with human
      embryonic stem cell-derived cardiomyocytes and showed that stromal and
      endothelial cells form vascular networks in vitro and improve cardiomyocyte
      engraftment. Here, we hypothesize that stromal cells regulate the angiogenic
      phenotype by modulating the extracellular matrix (ECM). Human marrow stromal
      cells (hMSCs) support the greatest degree of endothelial cell organization, at
      1.3- to 2.4-fold higher than other stromal cells tested. Stromal cells produce
      abundant ECM components in patches, including fibrillar collagen, hyaluronan, and
      versican. We identified two clonal hMSC lines that supported endothelial networks
      poorly and robustly. Interestingly, the pro-angiogenic hMSCs express high levels
      of versican, a chondroitin sulfate proteglycan that modulates angiogenesis and
      wound healing, whereas poorly angiogenic hMSCs produce little versican. When
      transplanted onto uninjured athymic rat hearts, patches with proangiogenic hMSCs
      develop ~ 50-fold more human vessels and form anastomoses with the host
      circulation, resulting in chimeric vessels containing erythrocytes. Thus, stromal
      cells play a key role in supporting vascularization of engineered human
      myocardium. Different stromal cell types vary widely in their proangiogenic
      ability, likely due in part to differences in ECM synthesis. Comparison of these
      cells defines an in vitro predictive platform for studying vascular development.

PMID- 21187006
TI  - Use of highly active antiretroviral therapy is increasing in HIV positive severe
      drug users.
AB  - BACKGROUND: Substance abuse greatly impacts the effectiveness of highly active
      antiretroviral therapy (HAART). We analyzed antiretroviral use in drug users
      positive for human immunodeficiency virus (HIV) that sought substance abuse
      treatment. METHODS: This cross-sectional study recruited 705 patients HIV
      positive (74.6% men) between 1997 and 2007. Patients were grouped by calendar
      periods when different HAART regimens were available in Spain (p1: 1997-1999,
      n=299; p2: 2000-2003, n=249; and p3: 2004-2007, n=157). RESULTS: The mean age at
      admission was 34 years; 94.7% had a past history of injection drug use (IDU) and
      67.7% were current IDUs. The average CD4 cell count was 399 cells/uL
      [interquartile range:203-632 cells/uL]. Lifetime prevalence of antiretroviral use
      was 59.4% (416/705; p1: 48.1%; p2: 64.6%; p3: 72.6%; p<0.05). The overall
      prevalence of antiretroviral use at admission was 40.7% (p1: 31.4%; p2: 41.0%;
      p3: 58.0%; p<0.05). In multivariate logistic regression analysis, age, calendar
      period, and non-IDU were predictors of antiretroviral use at admission. Among
      those taking antiretrovirals, 21.6% were on suboptimal HAART, mostly in the p1
      group. Overall, 44.6% of patients were taking protease inhibitor and non
      nucleoside reverse transcriptase inhibitor (PI-NNRTI), 21.9% were taking NRTI
      NNRTI, and 9.4% were taking three NRTIs. Although not significant, the three-NRTI
      regimen was associated with CD4 >350 cells/uL and HIV RNA <400 copies/mL.
      CONCLUSIONS: HAART use is steadily increasing in HIV positive heavy drug users.
      However, part of this population remains antiretroviral therapy-naive despite
      advanced immunodeficiency. Interventions that focus on integrating substance
      abuse with HIV/AIDS treatments are needed.

PMID- 21187007
TI  - Rates of initial virological suppression and subsequent virological failure after
      initiating highly active antiretroviral therapy: the impact of aboriginal
      ethnicity and injection drug use.
AB  - OBJECTIVES: To compare rates of initial virological suppression and subsequent
      virological failure by Aboriginal ethnicity after starting highly active
      antiretroviral therapy (HAART). METHODS: We conducted a retrospective cohort
      study of antiretroviral-naive HIV-patients starting HAART in January 1999-June
      2005 (baseline), followed until December 31, 2005 in Alberta, Canada. We compared
      the odds of achieving initial virological suppression (viral load <500 copies/mL)
      by Aboriginal ethnicity using logistic regression and, among those achieving
      suppression, rates of virological failure (the first of two consecutive viral
      loads >1000 copies/mL) by Aboriginal ethnicity using cumulative incidence curves
      and Cox proportional hazards models. Sex, injection drug use as an HIV exposure
      category (IDU), baseline age, CD4 cell count, viral load, calendar year, and
      HAART regimen were considered as potential confounders. RESULTS: Of 461 study
      patients, 37% were Aboriginal and 48% were IDUs; 71% achieved initial virological
      suppression and were followed for 730.4 person-years. After adjusting for
      confounding variables, compared to non-Aboriginals with other exposures, the odds
      of achieving initial virological suppression were lower for Aboriginal IDUs (odds
      ratio (OR)=0.33, 95% CI=0.19-0.60, p=0.0002), non-Aboriginal IDUs (OR=0.30, 95%
      CI=0.15-0.60, p=0.0006), and Aboriginals with other exposures (OR=0.38, 95%
      CI=0.21-0.67, p=0.0009). Among those achieving suppression, Aboriginals
      experienced higher virological failure rates >=1 year after suppression (hazard
      ratio=3.35, 95% CI=1.68-6.65, p=0.0006). CONCLUSIONS: Future research should
      investigate adherence among Aboriginals and IDUs treated with HAART and explore
      their treatment experiences to assess ways to improve outcomes.

PMID- 21187009
TI  - Options for sampling and stratification for national forest inventories to
      implement REDD+ under the UNFCCC.
AB  - BACKGROUND: Developing countries that are willing to participate in the recently
      adopted (16th Session of the Conference of Parties (COP) in Cancun) mitigation
      mechanism of Reducing emissions from Deforestation and Forest Degradation - and
      the role of conservation, sustainable management of forests and enhancement of
      forest carbon stocks (REDD+) - will have to establish a national forest
      monitoring system in order to assess anthropogenic forest-related greenhouse gas
      emissions by sources and removals by sinks. Such a system should support the
      Measurement, Reporting and Verification (MRV) requirement of the United Nations
      Framework Convention on Climate Change (UNFCCC) as the REDD+ mechanism is results
      based. A national forest inventory (NFI) is one potential key component of such
      an MRV system. Following the Decision adopted during the 15th Session of the COP
      in Copenhagen, the most recent Intergovernmental Panel on Climate Change (IPCC)
      Guidance and Guidelines should be used as a basis for estimating anthropogenic
      forest-related greenhouse gas emissions by sources and removals by sinks and
      changes in forest carbon stocks and area. RESULTS: First, we present the key
      indispensable elements of the IPCC Guidance and Guidelines that have been
      developed to fulfil the UNFCCC reporting requirements. This is done in order to
      set the framework to develop the MRV requirement in which a NFI for REDD+
      implementation could be developed. Second, within this framework, we develop and
      propose a novel scheme for the stratification of forest land for REDD+. Finally,
      we present some non-exhaustive optional elements within this framework that a
      country could consider to successfully operationalise and implement its REDD+
      NFI. CONCLUSION: Evidently, both the methodological guidance and political
      decisions on REDD+ under the UNFCCC will continue to evolve. Even so, and
      considering that there exists decades of experience in setting up traditional
      NFIs, developing a NFI that a country may use to directly support REDD+
      activities under the UNFCCC represents the development of a new challenge in this
      field. It is therefore important that both the scientific community and national
      implementing agencies acquaint themselves with both the context and content of
      this challenge so that REDD+ mitigation actions may be implemented successfully
      and with environmental integrity. This paper provides important contributions to
      the subject through our proposal of the stratification of forest land for REDD+.

PMID- 21187008
TI  - Quantitative automated microscopy (QuAM) elucidates growth factor specific
      signalling in pain sensitization.
AB  - BACKGROUND: Dorsal root ganglia (DRG)-neurons are commonly characterized
      immunocytochemically. Cells are mostly grouped by the experimenter's eye as
      "marker-positive" and "marker-negative" according to their immunofluorescence
      intensity. Classification criteria remain largely undefined. Overcoming this
      shortfall, we established a quantitative automated microscopy (QuAM) for a
      defined and multiparametric analysis of adherent heterogeneous primary neurons on
      a single cell base.The growth factors NGF, GDNF and EGF activate the MAP-kinase
      Erk1/2 via receptor tyrosine kinase signalling. NGF and GDNF are established
      factors in regeneration and sensitization of nociceptive neurons. If also the
      tissue regenerating growth factor, EGF, influences nociceptors is so far unknown.
      We asked, if EGF can act on nociceptors, and if QuAM can elucidate differences
      between NGF, GDNF and EGF induced Erk1/2 activation kinetics. Finally, we
      evaluated, if the investigation of one signalling component allows prediction of
      the behavioral response to a reagent not tested on nociceptors such as EGF.
      RESULTS: We established a software-based neuron identification, described
      quantitatively DRG-neuron heterogeneity and correlated measured sample sizes and
      corresponding assay sensitivity. Analysing more than 70,000 individual neurons we
      defined neuronal subgroups based on differential Erk1/2 activation status in
      sensory neurons. Baseline activity levels varied strongly already in untreated
      neurons. NGF and GDNF subgroup responsiveness correlated with their subgroup
      specificity on IB4(+)- and IB4(-)-neurons, respectively. We confirmed expression
      of EGF-receptors in all sensory neurons. EGF treatment induced STAT3
      translocation into the nucleus. Nevertheless, we could not detect any EGF induced
      Erk1/2 phosphorylation. Accordingly, intradermal injection of EGF resulted in a
      fundamentally different outcome than NGF/GDNF. EGF did not induce mechanical
      hyperalgesia, but blocked PGE2-induced sensitization. CONCLUSIONS: QuAM is a
      suitable if not necessary tool to analyze activation of endogenous signalling in
      heterogeneous cultures. NGF, GDNF and EGF stimulation of DRG-neurons shows
      differential Erk1/2 activation responses and a corresponding differential
      behavioral phenotype. Thus, in addition to expression-markers also signalling
      activity can be taken for functional subgroup differentiation and as predictor of
      behavioral outcome. The anti-nociceptive function of EGF is an intriguing result
      in the context of tissue damage but also for understanding pain resulting from
      EGF-receptor block during cancer therapy.

PMID- 21187010
TI  - Surprising negative association between IgG1 allotype disparity and anti
      adalimumab formation: a cohort study.
AB  - INTRODUCTION: The human monoclonal antibody adalimumab is known to induce an anti
      globulin response in some adalimumab-treated patients. Antibodies against
      adalimumab (AAA) are associated with non-response to treatment. Immunoglobulins,
      such as adalimumab, carry allotypes which represent slight differences in the
      amino acid sequences of the constant chains of an IgG molecule. Immunoglobulins
      with particular IgG (Gm) allotypes are racially distributed and could be
      immunogenic for individuals who do not express these allotypes. Therefore, we
      investigated whether a mismatch in IgG allotypes between adalimumab and IgG in
      adalimumab-treated patients is associated with the development of AAA. METHODS:
      This cohort study consisted of 250 adalimumab-treated rheumatoid arthritis (RA)
      patients. IgG allotypes were determined for adalimumab and for all patients. Anti
      idiotype antibodies against adalimumab were measured with a regular radio
      immunoassay (RIA), and a newly developed bridging enzyme linked immunosorbent
      assay (ELISA) was used to measure anti-allotype antibodies against adalimumab.
      The association between AAA and the G1m3 and the G1m17 allotypes was determined.
      For differences between groups we used the independent or paired samples t-test,
      Mann-Whitney test or Chi square/Fisher's exact test as appropriate. To
      investigate the influence of confounders on the presence or absence of AAA a
      multiple logistic regression-analysis was used. RESULTS: Adalimumab carries the
      G1m17 allotype. No anti-allotype antibodies against adalimumab were detected.
      Thirty-nine out of 249 patients had anti-idiotype antibodies against adalimumab
      (16%). IgG allotypes of RA patients were associated with the frequency of AAA:
      patients homozygous for G1m17 had the highest frequency of AAA (41%), patients
      homozygous for G1m3 the lowest frequency (10%), and heterozygous patients' AAA
      frequency was 14% (P = 0.0001). CONCLUSIONS: An allotype mismatch between
      adalimumab and IgG in adalimumab-treated patients did not lead to a higher
      frequency of AAA. On the contrary, patients who carried the same IgG allotype as
      present on the adalimumab IgG molecule, had the highest frequency of anti
      adalimumab antibodies compared to patients whose IgG allotype differed from
      adalimumab. This suggests that the allotype of adalimumab may not be highly
      immunogenic. Furthermore, patients carrying the G1m17-allotype might be more
      prone to antibody responses.

PMID- 21187011
TI  - Lack of plasma albumin impairs intravascular lipolysis and explains the
      associated free fatty acids deficiency and hypertriglyceridemia.
AB  - BACKGROUND: Abnormalities in lipid metabolism and transport are hallmarks in
      analbuminemic Nagase rats (NAR) and humans. Triglyceridemia is nearly 3- to 5
      fold higher in female NAR than in control Sprague-Dawley rats (SDR). Also, NAR
      present with a severe plasma free fatty acid (FFA) deficit. There are conflicting
      results regarding the mechanisms underlying NAR hypertriglyceridemia. OBJECTIVE:
      We aimed at investigating whether liver lipogenesis and triglyceride secretion
      rates into the plasma contribute to the hypertriglyceridemia in NAR. We also
      studied whether heparin or albumin administration would release the hypothesized
      lipolysis inhibition in NAR. METHODS: The incorporation of tritiated water into
      lipids and the linear accumulation rate of plasma triglycerides after Triton
      WR1339 injection were the measures of liver lipogenesis and triglyceride
      secretion rates. RESULTS: Lipogenesis (596 +/- 40 vs. 929 +/- 124 MUmol 3H2O/g/h)
      and triglyceride (4.25 +/- 1.00 vs. 7.04 +/- 1.68 mg/dL/min) secretion rates were
      slower (P <= 0.05) in fasted NAR than in control SDR. The injection of either
      heparin or albumin elicited an increase in NAR plasma FFA levels over time. FFA
      levels reached control levels 90 min after the albumin administration, increasing
      from 0.36 +/- 0.05 to 1.34 +/- 0.16 mEq/L (P <= 0.05). These results indicate
      that the lack of plasma albumin inhibits intravascular lipolysis and causes the
      FFA deficit observed in NAR. CONCLUSION: NAR hepatic triglyceride synthesis and
      output do not contribute to NAR hypertriglyceridemia. We propose that the lack of
      albumin diminishes intravascular lipolysis which reduces the plasma triglyceride
      removal rate and explain both NAR hypertriglyceridemia and FFA deficiency.

PMID- 21187012
TI  - Novel genes exhibit distinct patterns of function acquisition and network
      integration.
AB  - BACKGROUND: Genes are created by a variety of evolutionary processes, some of
      which generate duplicate copies of an entire gene, while others rearrange pre
      existing genetic elements or co-opt previously non-coding sequence to create
      genes with 'novel' sequences. These novel genes are thought to contribute to
      distinct phenotypes that distinguish organisms. The creation, evolution, and
      function of duplicated genes are well-studied; however, the genesis and early
      evolution of novel genes are not well-characterized. We developed a computational
      approach to investigate these issues by integrating genome-wide comparative
      phylogenetic analysis with functional and interaction data derived from small
      scale and high-throughput experiments. RESULTS: We examine the function and
      evolution of new genes in the yeast Saccharomyces cerevisiae. We observed
      significant differences in the functional attributes and interactions of genes
      created at different times and by different mechanisms. Novel genes are initially
      less integrated into cellular networks than duplicate genes, but they appear to
      gain functions and interactions more quickly than duplicates. Recently created
      duplicated genes show evidence of adapting existing functions to environmental
      changes, while young novel genes do not exhibit enrichment for any particular
      functions. Finally, we found a significant preference for genes to interact with
      other genes of similar age and origin. CONCLUSIONS: Our results suggest a strong
      relationship between how and when genes are created and the roles they play in
      the cell. Overall, genes tend to become more integrated into the functional
      networks of the cell with time, but the dynamics of this process differ
      significantly between duplicate and novel genes.

PMID- 21187015
TI  - [Analysis of two-dimension gel electrophoresis of human large cell lung cancer
      cell lines with different metastasis potentials].
AB  - BACKGROUND: Metastasis is not only the malignant characteristics of lung can-
      cer, but also the chief cause of failure to cure and high mortality of lung
      cancer. To better explore and understand the mechanism of lung cancer metastasis
      and to search for potential markers for early diagnosing and reversing lung
      cancer metastasis, differential proteomic analysis is conducted in two human
      large cell lung cancer cell lines with high metastasis potentials (L9981) and low
      metastasis potentials (NL9980) by two-dimension gel electrophoresis (2-DE).
      METHODS: The total proteins of the two cell lines were separated by immobilized
      pH gradient (IPG)-based 2-DE. The differentially expressed proteins of the two
      cell lines were analyzed using image analysis software. RESULTS: A high
      resolution and reproducible 2-DE image was successfully obtained. Average
      deviations for protein position in IEF direction were (0.858+/-0.076)mm and
      (1.514+/-0.127)mm in SDS-PAGE direction. The relative standard deviation for
      protein volume was (12.06+/-0.580)% in L9981 and (12.22+/-0.640)% in NL9980. The
      average total number of protein spots was 902+/-169 in L9981 cells and 941+/-173
      in NL9980 cells in three repeated experiments. Image analysis of siliver-stained
      2-DE image revealed that 4 protein spots had significant differential expressions
      in L9981 and NL9980 (student's t-test, P < 0.05). Fifteen protein spots were only
      detected in L9981, and 27 protein spots were only detected in NL9980.
      CONCLUSIONS: The results in this study suggest that an obviously differential
      proteomic expression exists between the human high- and low-metastatic large cell
      lung cancer cell lines. It will be helpful to further understand the molecular
      mechanisms of lung cancer invasion and metastasis, and provide new experimental
      evidence for searching metastatic-related molecule of lung cancer.

PMID- 21187013
TI  - Bio-informatics analysis of a gene co-expression module in adipose tissue
      containing the diet-responsive gene Nnat.
AB  - BACKGROUND: Obesity causes insulin resistance in target tissues - skeletal
      muscle, adipose tissue, liver and the brain. Insulin resistance predisposes to
      type-2 diabetes (T2D) and cardiovascular disease (CVD). Adipose tissue
      inflammation is an essential characteristic of obesity and insulin resistance.
      Neuronatin (Nnat) expression has been found to be altered in a number of
      conditions related to inflammatory or metabolic disturbance, but its
      physiological roles and regulatory mechanisms in adipose tissue, brain,
      pancreatic islets and other tissues are not understood. RESULTS: We identified
      transcription factor binding sites (TFBS) conserved in the Nnat promoter, and
      transcription factors (TF) abundantly expressed in adipose tissue. These include
      transcription factors concerned with the control of: adipogenesis (Ppargamma,
      Klf15, Irf1, Creb1, Egr2, Gata3); lipogenesis (Mlxipl, Srebp1c); inflammation
      (Jun, Stat3); insulin signalling and diabetes susceptibility (Foxo1, Tcf7l2). We
      also identified NeuroD1 the only documented TF that controls Nnat expression. We
      identified KEGG pathways significantly associated with Nnat expression, including
      positive correlations with inflammation and negative correlations with metabolic
      pathways (most prominently oxidative phosphorylation, glycolysis and
      gluconeogenesis, pyruvate metabolism) and protein turnover. 27 genes, including;
      Gstt1 and Sod3, concerned with oxidative stress; Sncg and Cxcl9 concerned with
      inflammation; Ebf1, Lgals12 and Fzd4 involved in adipogenesis; whose expression
      co-varies with Nnat were identified, and conserved transcription factor binding
      sites identified on their promoters. Functional networks relating to each of
      these genes were identified. CONCLUSIONS: Our analysis shows that Nnat is an
      acute diet-responsive gene in white adipose tissue and hypothalamus; it may play
      an important role in metabolism, adipogenesis, and resolution of oxidative stress
      and inflammation in response to dietary excess.

PMID- 21187016
TI  - [Growth inhibition of NS-398 combined with cisplatin on human lung adenocarcinoma
      cells and its mechanism].
AB  - BACKGROUND: In recent years, many investigations have showed that COX-2
      inhibitors not only inhibit the growth of tumor cells but also enhance the
      cytotoxicity of anticancer drugs, such as NS-398, a selective COX-2 inhibitor.
      But the effect of NS-398 combined with chemotherapy agent cisplatin on growth of
      lung adenocarcinoma cells and its mechanism are still unknown. The aim of this
      study is to investigate the effect of NS-398 combined with cisplatin on
      proliferation of human lung adenocarcinoma cell lines, and to explore their
      mechanisms. METHODS: Synergistic effect of NS-398 and cisplatin on proliferation
      of human lung adenocarcinoma cell lines was detected by MTT growth assay, and
      data were analyzed by SPSS general linear models procedure to determine the IC50
      of each drug alone. Combined index (CI) was analyzed to determine the combined
      effect of drugs. Apoptosis and cell cycle distribution were detected by
      fluorescence staining of Acridine orange (AO) and Ethidium bromide (EB) and flow
      cytometry. RESULTS: The various concentration of NS-398 in combination with
      cisplatin resulted in the reduction of IC50 of cisplatin by 48.25%-62.44% in A549
      cells, and by 43.34%-69.61% in SPC-A-1 cells. The CI of NS-398 and cisplatin in
      the two cell lines ranged from 0.4 to 0.9, which indicated that they acted in
      slight synergistic to synergistic pattern. The apoptotic rate at 24h and 48h in
      the combined groups was significantly higher than those of the control groups,
      and the S-phase cell fractions at 48h and 72h were obviously higher than those of
      the control groups. There was a positive correlation between apoptotic rate and S
      phase cell fraction in the combined groups (r=0.882,P= 0.01). CONCLUSIONS: NS-398
      can improve growth inhibition of cisplatin on lung adenocarcinoma cells, and the
      two agents act in synergistic way. This synergistic effect may be related to
      apoptosis pathway.

PMID- 21187017
TI  - [Study on the association between genetic polymorphism of CYP2E1, GSTM1 and
      susceptibility of lung cancer].
AB  - BACKGROUND: Lung cancer is the leading cause of malignant tumor death among
      Chinese population. It has been known that the development of lung cancer may be
      associated with genetic po-lymorphism of some lung cancer related genes. The aim
      of this study is to evaluate the relationship between genetic polymorphism of
      metabolizing enzymes and susceptibility of lung cancer in Chinese population.
      METHODS: Polymorphism of CYP2E1 RsaI/PstI and GSTM1 was detected in 99 patients
      with lung cancer and 66 patients with benign pulmonary disease by PCR-RFLP and
      PCR. The association between genetic polymorphism and susceptibility of lung
      cancer was analyzed. RESULTS: No significant difference in three RsaI/PstI
      genotype distribution of CYP2E1 was found between lung cancer group and control
      group (Chi-Square=1.374, P=0.241). (2) The frequency of GSTM1-null genotype in
      lung cancer group was significantly higher than that in control group (57.6% vs
      40.9%, Chi-Square=4.401, P=0.036). (3) The individuals who carried with GSTM1
      null genotype had a 1.96 fold increased risk of lung cancer (OR=1.96, 95%CI=1.042
      3.689, P=0.037) than those who carried with GSTM1-present genotype. (4) When data
      were stratified by smoking status, the smokers who carried with c1/c1 genotype
      had a significantly higher risk of lung cancer (OR=3.525, 95%CI=1.168- 10.638,
      P=0.025) than those never-smokers who carried with at least one c2 allel. (5)
      When combination of polymorphism of CYP2E1 RsaI/PstI genotype and GSTM1 genotype
      was analyzed, compared with individuals who had concurrent present of GSTM1 and
      at least one c2 allel genotype, the risk of lung cancer for combination of GSTM1
      null and c1/c1 genotype was increased significantly (OR=3.449, 95%CI=1.001-
      11.886, P=0.050). Considering smoking status, compared with never-smokers who had
      concurrent present of GSTM1 and at least one c2 allel genotype, the risk of lung
      cancer for combination of GSTM1 null and c1/c1 genotype was remarkably increased
      (OR=11.553, 95%CI=1.068-124.944, P=0.044), as well as that for combination of
      GSTM1 null and at least one c2 allel genotype (OR=13.374, 95%CI=1.258-142.166, P=
      0.032). CONCLUSIONS: (1)GSTM1 null genotype is an important factor associated
      with increased risk of lung cancer. (2) The combination of c1/c1 and GSTM1-null
      genotype can remarkably increase risk of lung cancer both in smokers and non
      smokers.

PMID- 21187014
TI  - A var2 leaf variegation suppressor locus, SUPPRESSOR OF VARIEGATION3, encodes a
      putative chloroplast translation elongation factor that is important for
      chloroplast development in the cold.
AB  - BACKGROUND: The Arabidopsis var2 mutant displays a unique green and white/yellow
      leaf variegation phenotype and lacks VAR2, a chloroplast FtsH metalloprotease. We
      are characterizing second-site var2 genetic suppressors as means to better
      understand VAR2 function and to study the regulation of chloroplast biogenesis.
      RESULTS: In this report, we show that the suppression of var2 variegation in
      suppressor line TAG-11 is due to the disruption of the SUPPRESSOR OF VARIEGATION3
      (SVR3) gene, encoding a putative TypA-like translation elongation factor. SVR3 is
      targeted to the chloroplast and svr3 single mutants have uniformly pale green
      leaves at 22 degrees C. Consistent with this phenotype, most chloroplast proteins
      and rRNA species in svr3 have close to normal accumulation profiles, with the
      notable exception of the Photosystem II reaction center D1 protein, which is
      present at greatly reduced levels. When svr3 is challenged with chilling
      temperature (8 degrees C), it develops a pronounced chlorosis that is accompanied
      by abnormal chloroplast rRNA processing and chloroplast protein accumulation.
      Double mutant analysis indicates a possible synergistic interaction between svr3
      and svr7, which is defective in a chloroplast pentatricopeptide repeat (PPR)
      protein. CONCLUSIONS: Our findings, on one hand, reinforce the strong genetic
      link between VAR2 and chloroplast translation, and on the other hand, point to a
      critical role of SVR3, and possibly some aspects of chloroplast translation, in
      the response of plants to chilling stress.

PMID- 21187018
TI  - [A preliminary study of antineoplastic effects of Anticancer Ketonon on lung
      cancer in mice].
AB  - BACKGROUND: It has been proved that Tanshinone has obvious anticancer effect, but
      its mechanisms of anticancer are still unknown. Anticancer Ketonon is complex
      antitumor drug which Tanshinone is combined with other anticancer elements. This
      study aims to explore the antineoplastic effects of Anticancer Ketonon on Lewis
      lung cancer and the mechanisms in mice. METHODS: The mice were divided into three
      groups: Ketonon group, 5-fluorouracil (5-Fu) group and control group. The former
      two groups were treated with responsive drugs after subcutaneous inoculation of
      Lewis lung cancer. The last group was only treated with normal saline after
      inoculation. Apoptosis index and cell cycle were measured by flow cytometry.
      RESULTS: Two experiments were carried out in male and female mice respectively.
      The tumor inhibitory rates of Anticancer Ketonon were 38.9% and 32.2%
      respectively, those of 5-FU were 59.6% and 53.9%. Compared with those of control
      groups, the tumor weights in Ketonon group and 5-Fu group were statistically
      decreased (P < 0.05). Metastasis rates of the lung in the three groups were not
      statistically different (P > 0.05). The apoptosis index of Ketonon group was
      significantly higher than that of control group (P < 0.05), but the cell cycle
      was not statistically changed compared with that of control group (P > 0.05).
      CONCLUSIONS: Anticancer Ketonon has antineoplastic effect on Lewis lung cancer in
      mice and the mechanism may be associated with inducing apoptosis of tumor cells.

PMID- 21187019
TI  - [STAT3 and ras-MAPK signal transduction pathway in non-small cell lung cancer].
AB  - BACKGROUND: Biochemical and genetic researches suggest that ras protein plays an
      important role in transduction process of cell proliferation differentiation
      signals from activated transmembrane receptors to substream protein kinases. This
      study is to explore the expression of ras, p38, both of which are members of MAPK
      (mitogen activated protein kinases) signal transduction pathway, and STAT3
      (signal transducer and activator of transcription 3) in non-small cell lung
      cancer, and the association among them. METHODS: Forty-two resected lung cancer
      and paracancerous lung tissue samples were used to determine the protein
      expression of ras, p38 and STAT3 with Western blot, the mRNA expression of p38
      and STAT3 in lung cancer tissues of various ras protein expression with RT-PCR.
      The location of p38 and STAT3 in lung cancer tissues was revealed with
      immunofluorescent staining. RESULTS: The relative protein expressions of ras, p38
      and STAT3 were 0.6012, 0.6724, 0.5119 in cancer tissues, and 0.2793, 0.3071,
      0.1917 in paracancerous lung tissues, respectively (P < 0.01). The protein and
      mRNA expressions of p38 and STAT3 ( 0.7624 and 0.6262; 1.0309 and 1.0538) in
      cancer tissues with higher ras protein expression were remarkably higher than
      those with lower ras protein expression (0.4715 and 0.2569; 0. 6569 and 0.3437, P
      < 0.01). There was a significant correlation between the expression of ras, p38
      and STAT3 (correlation coefficient: 0.809 and 0.842, P < 0.01), and so was the
      p38 and STAT3 (correlation coefficient: 0.829, P < 0.01). CONCLUSIONS: Abnormal
      expressions of STAT3 and some factors of ras-MAPK signal transduction pathway
      exist in the oncogenesis and development of non-small cell lung cancer, and many
      of them may have crosstalk.

PMID- 21187020
TI  - [A study on the relationship between VEGF-C expression and lymphatic metastasis
      in non-small cell lung cancer].
AB  - BACKGROUND: It has been known that an intensive relationship exists between the
      recurrence or metastasis and angiogenesis and lymphangiogenesis in patients with
      non-small cell lung cancer (NSCLC), but it is uncertain whether there is
      relationship between VEGF-C expression and angiogenesis and lymphangiogenesis in
      NSCLC tissues. This study is to explore the relationship among VEGF-C expression
      and angiogenesis and lymphangiogenesis and lymphatic metastasis in NSCLC tissues.
      METHODS: The expression of VEGF-C was detected in 78 lung cancer tissues with or
      without lymphatic metastasis by LSAB methods. Microvessel density (MVD) and
      lymphatic microvessel density (LMVD) were determined in the same patients by CD31
      and VEGFR-3 respectively. RESULTS: The positive rate of VEGF-C expression was
      52.6% (41/78) in NSCLC tissues; VEGF-C expression in lung cancer tissues with
      lymphatic metastasis (30/43, 69.7%) was significantly higher than that without
      lymphatic metastasis (11/35, 30.3%) (P < 0.05); LMVD in the group without VEGF-C
      expression (23.4+/-2.3) was significantly lower than that with VEGF-C expression
      (43.2+/-4.1) (P < 0.05), there was no singificant difference in MVD between the
      two groups (31.1+/-1.8 vs 28.1+/- 3.2) (P > 0.05); the MVD and LMVD in lung
      cancer tissues with lymphatic metastasis (33.6+/-1.1 and 41.3+/-3.3 respectively)
      were significantly higher than those without lymphatic metastasis (18.7+/-1.8 and
      25.7+/- 2.1 respectively) (P < 0 05). CONCLUSIONS: The results suggest that VEGF
      C may play an important role in the lymphatic metastasis of lung cancer through
      the regulation of lymphangiogenesis.

PMID- 21187021
TI  - [MRP expression in non-small cell lung cancer and normal lung tissues and its
      prognostic significance].
AB  - BACKGROUND: Drug-resistance of tumor is the main reason of the failure of che
      motherapy. Much attention has been paid to the expression of multidrug resistance
      associated protein (MRP) and its mechanism of drug-resistance in non-small cell
      lung cancer (NSCLC). Results of this research will contribute to reversing drug
      resistance and improving curative effect. The aim of this study is to investigate
      the relationships between the expression of MRP and clinicopathological
      parameters and prognosis in patients with NSCLC. METHODS: Expression of MRP was
      detected in 62 cases of paraffin-embedded NSCLC samples by streptavidin-biotin
      peroxidase complex immunohistochemistry method, as well as in 30 fresh cases of
      NSCLC samples and corresponding normal lung tissues by immunohistochemistry and
      Western blot. RESULTS: MRP expression of NSCLC tissues was significantly higher
      than that of normal lung tissues. The survival time of patients with negative MRP
      expression was (69.81+/-17.41) months, and that of patients with positive MPR
      expression was (25.38+/-4.46) months (P=0.0156). This statistically significant
      relationship between the survival time and prognosis was also showed in squamous
      cell carcinoma patients (P=0.015), but not in adenocarcinoma. Multivariate COX
      model analysis suggested that the survival time was significantly related to
      lymphatic metastasis (P=0.038) and expression of MRP (P=0.035). CONCLUSIONS: MRP
      expression in NSCLC is significantly higher than that in the normal lung tissues.
      The mean survival time of patients with negative MRP expression is remarkably
      longer than that of patients with positive MRP expression. MRP expression may be
      an independent prognostic factor.

PMID- 21187022
TI  - [Comparison between clinical and surgical-pathological TNM staging in patients
      with lung cancer].
AB  - BACKGROUND: The accuracy of clinical TNM staging correlates with appropriate
      treatment in patients with lung cancer. The aim of this study is to evaluate the
      agreement between clinical and surgical-pathological staging in patients with
      lung cancer and analyze its cause in detail. METHODS: One hundred and fifty
      patients with lung cancer treated surgically from 2000 were enrolled randomly.
      Clinical and surgical-pathological staging of them were made respectively
      according to the International System for Staging Lung Cancer newly revised by
      UICC. Then concordance was determined between the two staging results with Kappa
      value, and difference in coincident rate was analyzed among subgroups of T
      staging. RESULTS: For T staging, the agreement was excellent (Kappa value=0.729),
      however, the coincident rate of T3 or T4 was significantly lower than that in T1
      or T2 group (P < 0.01). The agreement of N staging was poor (Kappa value=0.108),
      followed by a disappointed conformity of TNM staging (Kappa value=0.287).
      CONCLUSIONS: Clinical T staging based on CT can indicate the location and size of
      primary tumor precisely. But the borderline may be difficult to estimate when
      tumor site is near chest wall or mediastinum, so some patients with clinical T4
      still have chances to receive complete resection. The conformity of N staging is
      rather poor. The key point to improve the accuracy of clinical TNM staging should
      be to seek more reliable techniques for evaluating N status.

PMID- 21187023
TI  - [Tracheo-carinal reconstruction, bronchoplasty and vascular reconstruction in the
      treatment of lung cancer].
AB  - BACKGROUND: Reconstruction of carina, bronchoplasty and arterioplasty are widely
      used to extend the indication of lung cancer operation. Because these procedures
      preserve as many healthy lung tissues as possible, their therapeutic effect is
      better than pneumonectomy in many central lung cancer cases with poor
      cardiopulmonary function. The aim of this study is to explore the feasibility and
      indication of extended resection in selected patients with centrally located lung
      cancer. METHODS: From November, 1979 to January, 2003, lobectomy or pneumonectomy
      combined with extended resection of tracheo-carina, bronchus or vessels were
      performed in 50 patients with centrally located lung cancer. Tracheo-carinal
      reconstruction and bronchoplasty were performed in 48 cases, and pulmonary
      arterioplasty in 2 cases. RESULTS: Postoperative complications occurred in 4
      patients (8.0%), and operative death occurred in 2 patients (4.0%). All the 48
      patients were followed up from 1 to 10 years. The 1-, 3-, 5- and 10-year survival
      rate was 89.4% (42/47), 57.1% (20/35), 42.1% (8/19) and 25.0%(2/8) respectively.
      CONCLUSIONS: Extended pulmonary resection combined with tracheo-carinal
      reconstruction, bronchoplasty and vascular reconstruction is feasible for
      selected patients with centrally located lung cancer. It is helpful to prolong
      the long-term survival of patients with lung cancer.

PMID- 21187024
TI  - [Hydroxycamptothecine and ifosfamide as second-line therapy in non-small cell
      lung cancer after prior treatment with platinum-based regimens].
AB  - BACKGROUND: Multiple drug-resistance to platinum is one of important influencing
      factors failure to chemotherapy in the treatment of non-small cell lung cancer
      (NSCLC). To study and explore the effective chemotherapy drugs and
      chemotherapeutic regimens inhibiting or reversing multiple drug-resistance is the
      popular problem in lung cancer clinic. The aim of this study is to evaluate the
      chemotherapeutic response and toxicities of combination of hydroxycamptothecine
      (HCPT) and ifosfamide (IFO) in patients with relapsed NSCLC after pretreatment
      with platinum-based regimens. METHODS: Patients with NSCLC, performance status
      (PS) < or =2, with history of prior platinum-based chemotherapy and without
      impaired haematopoietic and organ function were eligible. Chemotherapy was
      administered as follows: HCPT 6-8mg/m2 from 1st to 5th day, IFO 1.2mg/m2 from the
      1st to 3rd day which was recycled every 3 weeks. RESULTS: From June 2002 to
      December 2003, 69 patients were enrolled and 53 were evaluable for response and
      all 69 for toxicity. The total response rate was 11.3% (6/53), stable disease was
      39.6% (21/53) and progressive disease was 49.1% (26/53). The main side-effect was
      haematological toxicity, with grade III-IV (G3-4) neutropenia in 12 patients, G3
      thrombocytopenia and anemia in 4 and 4 patients respectively. Non-hematological
      toxicities were negligible. Alopecia rate was 87.0%. CONCLUSIONS: The combination
      of HCPT and IFO is a tolerable and effective combination regimen to apply in the
      treatment of cisplatin-pretreated NSCLC patients.

PMID- 21187025
TI  - [Analysis of concurrent chemoradiotherapy in patients with stage III non-small
      cell lung cancer after two cycles of induction chemotherapy].
AB  - BACKGROUND: Recently chemoradiotherapy becomes a standard treatment of un
      resectable advanced non-small cell lung cancer (NSCLC) instead of radiotherapy
      alone. This study is to evaluate the clinical effect and toxicities of concurrent
      chemoradiotherapy in patients with stage III NSCLC after 2 cycles of induction
      chemotherapy with cisplatin-based regimens. METHODS: Ninety-two patients with
      stage III NSCLC were divided randomly into two groups: forty-seven patients
      received concurrent chemoradiotherapy (chemoradiotherapy group), the other 45
      patients received only radiotherapy (radiotherapy group). For both groups, the
      same radiation technic was given with the conventional fraction. The total dose
      was 60-65Gy/30-33Fr/6-6.5Wk. For the chemoradiotherapy group, the patients were
      also given with concurrent chemotherapy (navelbine 15-18mg/m2 on the 1st and 8th
      day, cisplatin 60mg/m2 on the 1st day). RESULTS: The response rate in the
      chemoradiotherapy group was similar to that in the radiotherapy group (59.6% vs
      51.5%, P > 0.05), but the complete response rate in the chemoradiotherapy group
      was significantly higher than that in the radiotherapy group (14.9% vs 6.7%, P <
      0.05). The 1- and 2-year survival rates in the chemoradiotherapy group were
      similar to those in the radiotherapy group (65.9% and 42.5% vs 53.3% and 33.3%, P
      > 0.05). The 1- and 2-year local control rates in the chemoradiotherapy group
      were significantly higher than those in the radiotherapy group (63.8% and 53.2%
      vs 51.1% and 44.4%, P < 0.05). The incidences of grade III-IV radiation
      esophagitis and leukopenia in the chemoradiotherapy group were significantly
      higher than those in the radiotherapy group (21.2% and 12.7% vs 4.4% and 0, P <
      0.01). CONCLUSIONS: Concurrent chemoradiotherapy has the potential of improving
      the survival rate of stage III NSCLC, it can also increase the acute toxic
      effect, but all patients can tolerate this treatment regimen.

PMID- 21187026
TI  - [The efficacy of vinorelbine plus cisplatin in the treatment of 48 cases of
      advanced non-small cell lung cancer].
AB  - BACKGROUND: Chemotherapy is one of the important treatment methods for advanced
      non-small cell lung cancer (NSCLC). The aim of this study is to evaluate the
      efficacy of the combination of vinorelbine (NVB) and cisplatin (DDP) in the
      treatment of advanced NSCLC. METHODS: Forty-eight patients with stage IIIB and IV
      NSCLC were treated with NVB (25mg/m2 ,iv,d1 and d8) and DDP (40mg/m2, d1 and d2).
      RESULTS: The overall response rate (RR) was 48%, median survival time was 10
      months, and 1-year survival rate was 35%. The RR of patients with first-line
      chemotherapy was 55%, median survival time was 11 months, the RR of patients with
      second-line chemotherapy was 35%, median survival time was 8 months; the RR of
      patients with stage IIIB was 54%, median survival time was 10 months, the RR of
      patients with stage IV was 41%, median survival time was 9 months. The main
      toxicities were myelosuppression, nausea, vomiting and phlebitis. CONCLUSIONS:
      The combination of NVB and DDP in the treatment of advanced NSCLC has a high
      response rate and tolerable side effects, which can be adopted as the first-line
      treatment of advanced NSCLC, or the second line treatment that still need further
      studies.

PMID- 21187027
TI  - [Analysis of main pathogen of deep fungal infection in patients with lung cancer
      by FCM].
AB  - BACKGROUND: Deep fungal infection is one of the important complications and
      causes of death in late stage patients with lung cancer, to explore and analyze
      the pathogen of deep fungal infection is helpful to early diagnose and treat deep
      fungal infection in patients with lung cancer. The aim of this study is to
      investigate the changes and pathogenicity of the main pathogen of deep fungal
      infection in patients with lung cancer. METHODS: Total DNA per cell,
      proliferation index (PI) and cell cycle of the main pathogen of deep fungal
      infection were analyzed in patients with lung cancer by FCM. RESULTS: Histograms
      of stationary-growth-phase Candida albicans isolates demonstrated that the
      majority of population of the fungus were at the G0/G1 phase of cell cycle. There
      was no significant difference in cell proportion of G0/G1, G2/M phases and the
      total DNA content per cell of strains between the lung cancer and normal control
      groups. The cell proportion of S phase and PI in lung cancer group were
      remarkably higher than those in control group (P=0.040, P=0.038). CONCLUSIONS:
      The cell proportion at DNA composition phase of the main pathogen-Candida
      albicans significantly increases, the proliferation activity gets strengthened
      and the pathogenicity changes in deep fungal infection of patients with lung
      cancer.

PMID- 21187028
TI  - [In vitro fertilization: innovative research to give life].

PMID- 21187029
TI  - [Dendritic organization and functional characteristics of visually evoked inputs
      to cortical neurons in vivo].

PMID- 21187030
TI  - [The hepatitis C virus can be cultured in primary human hepatocytes, at last!].

PMID- 21187031
TI  - [Human pain channelopathies].

PMID- 21187032
TI  - [Transcriptional regulation by the coactivator TFIID].

PMID- 21187033
TI  - [Identification of basal cell carcinoma initiating cells].

PMID- 21187034
TI  - [CDK4, a specific target in the treatment of lung adenocarcinomas mutated for
      KRAS].

PMID- 21187035
TI  - [Mobile elements jump between parasites and vertebrate hosts].

PMID- 21187036
TI  - [Mitotic spindle and asymmetric stem cell division].

PMID- 21187037
TI  - [Mesenchymal-to-epithelial transition: a necessary initial step towards
      reprogrammation of fibroblasts].

PMID- 21187038
TI  - [Targeting oxidative metabolism to treat leukemia?].

PMID- 21187039
TI  - [Nucleosome-depleted regions in promoters: consequences on robustness of
      transcriptional activation].

PMID- 21187040
TI  - [Adaptation to high altitudes: on which genes was selective pressure exercised?].

PMID- 21187041
TI  - [An "ariditary" form of ovarian cancer].

PMID- 21187043
TI  - [Prolactin and its cleaved 16 kDa fragment].
AB  - Prolactin, owing to its origins, actions and molecular forms, is an ubiquitous
      and pleiotropic hormone. Indeed prolactin, initially thought to be essentially
      synthesized in the hypophysis, is also produced by several tissues in mammals. It
      is involved in more than 300 different biological activities, such as
      reproduction, developmental immunity and behaviour. It is also described under
      several molecular forms resulting from co- or post-translational modifications
      and enzymatic cleavage. Among these, the 16 kDa form, derived from native
      prolactin, has received particular attention because of its inhibitory effect on
      angiogenesis. Recent results have suggested an important role of tissue enzymes
      in the production of this form in several tissues (retina, myocardium and mammary
      gland). The cleavage leading to the production of 16 kDa prolactin may occur
      outside the cells, in the interstitial medium and therefore in the vicinity of
      blood capillaries. This process implies tissue-specific mechanisms of regulation.
      A better knowledge of the location of the cleavage and of the regulation of these
      activities of the cleaving enzymes is now essential for controlling the
      processes. This knowledge will allow a better understanding of the relationships
      between some pathologies (cardiomyopathy, pre-eclampsia, retinopathy) and
      modification of the production of the anti-angiogenic form of prolactin.

PMID- 21187044
TI  - [mTOR, the mammalian target of rapamycin].
AB  - The discovery of rapamycin from a soil sample on Easter Island in the mid 60's
      marked the beginning of an exciting field of research in cell biology and
      medicine. While it was first used as an antifungal and as an immunosuppressive
      drug, more recent studies confirmed rapamycin's antiproliferative properties over
      a variety of solid tumors. Research aimed at identifying its mechanism of action
      uncovered mTOR (mammalian target of rapamycin), a protein kinase that regulates
      mRNA translation and protein synthesis, an essential step in cell division and
      proliferation. Recent evidence suggests a more complex role for mTOR in the
      regulation of several growth factor-stimulated protein kinases, including the
      proto-oncogene Akt. This article reviews mTOR function and regulation, and
      briefly details the future challenges for anti-cancer therapies based on mTOR
      inhibition.

PMID- 21187045
TI  - [Robust differentiation of fetal hepatocytes from human embryonic stem cells and
      iPS].
AB  - Hepatocyte transplantation is considered as an alternative to organ
      transplantation in particular for the treatment of liver metabolic diseases.
      However, due to the difficulties to obtain a large number of hepatocytes, new
      sources of cells are needed. These cells could be either of hepatic origin
      (hepatic stem cells) or extrahepatic such as mesenchymal stem cells or
      pluripotent stem cells (human embryonic stem cells [hESC] or iPS). We developed a
      new method to differentiate hESCs into fetal hepatocytes. These conditions
      recapitulate the main liver developmental stages, using fully defined medium
      devoid of animal products or unknown factors. The differentiated cells express
      many fetal hepatocytes markers (cytochrome P450 3A7, albumin, alpha-1
      antitrypsin, etc.). The cells display specific hepatic functions (ammonia
      metabolism, excretion of indocyanin green) and are capable to engraft and express
      hepatic proteins two months after transplantation into newborn uPAxrag2gc-/-
      mouse liver. We have also showed that this approach is transposable to human iPS,
      and further studies on animal models will allow us to compare the in vivo
      potential of these two sources of pluripotent cells. Finally, only studies on
      large animals such as nonhuman primates will validate an eventual clinical
      application.

PMID- 21187046
TI  - [The greater RTK/RAS/ERK signalling pathway: how genetics has helped piece
      together a signalling network].
AB  - Cells respond to changes in their environment, to developmental cues and to
      pathogen aggression through the action of a complex network of proteins. These
      networks can be split into a multitude of signalling pathways that relay signals
      from the microenvironment to the cellular components involved in eliciting a
      specific response. Perturbations in these signalling processes are at the root of
      multiple pathologies, the most notable of these being cancer. The study of
      receptor tyrosine kinase (RTK) signalling led to the first description of a
      mechanism whereby an extracellular signal is transmitted to the nucleus to induce
      a transcriptional response. Genetic studies conducted in drosophila and nematodes
      have provided key elements to this puzzle. Here, we briefly discuss the poorly
      known contribution of these multicellular organisms to our understanding of what
      has become a prototype in cell signalling as well as to the more recent
      description of the complex network of regulators that is now known to govern
      RTK/RAS/ERK signalling.

PMID- 21187047
TI  - [Pendrin: its role in kidney function and hypertension].
AB  - Loss-of-function mutations of the pendrin gene are responsible for a pathology
      characterized by dysfunctions of thyroid and inner ear. However, it rapidly
      appeared after its discovery that the anion exchanger encoded by this gene plays
      a central role in kidneys. This brief review pictures the evolution of our
      knowledge regarding renal functions of pendrin, with a special emphasis to its
      recently identified roles in the maintenance of sodium homeostasis and blood
      pressure.

PMID- 21187048
TI  - [The cytochrome bc1 complex in the mitochondrial respiratory chain functions
      according to the Q cycle hypothesis of Mitchell: the proof using a stochastic
      approach?].
AB  - The bc1 complex is a central complex in the mitochondrial respiratory chain. It
      links the electrons transfer from ubiquinol (or coenzyme Q) to cytochrome c and
      proton translocation across the inner mitochondrial membrane. It is widely agreed
      that the "Q-cycle mechanism" proposed by Mitchell correctly describes the bc1
      complex working. It is based on an unexpected separation of the two electrons
      coming from the coenzyme Q bound at the Q0 site of the bc1 complex. Using the
      stochastic approach of Gillespie and the known spatial structure of bc1 complexes
      with the kinetic parameters described by Moser and Dutton we demonstrated the
      natural emergence of the Q-cycle mechanism and the quasi absence of short
      circuits in the functional dimer of bc1 complex without the necessity to invoke
      any additional mechanism. This approach gives a framework which is well adapted
      to the modelling of all oxido-reduction reactions of the respiratory chain
      complexes, normal or mutant.

PMID- 21187049
TI  - [Resistance to immunization].
AB  - Despite a well documented efficacy and a generally good adhesion of a large
      majority of the lay population and health care professionals as well,
      immunization is still the object of controversies. It affects several vaccines
      against hepatitis B, influenza, BCG, pertussis and measles. In most cases,
      polemics on vaccination result from a temporal association between a vaccination
      and the revelation of a serious disease, when the immunization is performed at
      the peak of incidence of the disease. Controversies can also be initiated by
      scientific publications, even though these are often biased, by a
      misinterpretation or the absence of official positions from the health care
      authorities, or by justice decisions, whose criteria differ from the scientists'
      ones and are therefore difficult to understand for the lay public. Furthermore,
      the scientific demonstration of the exclusion of a risk is difficult to obtain.
      In the past, it appeared to be very difficult to stop controversies. Improving
      the communication is the main issue, towards lay public as well as health care
      professionals. This implies to learn how to better use the media, to motivate and
      educate professionals who administer vaccine, and anticipate the eventuality of a
      temporal relationship between vaccination and occurrence of a serious disease by
      an improved management of the pharmacovigilance system.

PMID- 21187050
TI  - [The palladium, a magic catalyst for the chemists].

PMID- 21187051
TI  - [Palladium and organic synthesis: a useful meeting rewarded].

PMID- 21187052
TI  - [From medical imaging to image-guided therapy].
AB  - This survey on medical imaging provides a look into three major components. The
      first one deals with the full steps through which it must be apprehended: from
      the sensors to the reconstruction, from the image analysis up to its
      interpretation. The second aspect describes the physical principles used for
      imaging (magnetic resonance, acoustic, optics, etc.). The last section shows how
      imaging is involved in therapeutic procedures and in particular the new physical
      therapies. All along this paper, the research perspectives are sketched.

PMID- 21187053
TI  - [Making good use of exome sequencing].

PMID- 21187054
TI  - First record of larval Pseudoproleptus sp. (Nematoda: Cystidicolidae) in fish
      host.
AB  - Infective third-stage larvae of the cystidicolid nematode Pseudoproleptus sp.
      were found encapsulated in the mesentery of the freshwater fish Satanoperca
      jurupari Heckel (Cichlidae) from the Guama River, close to the Amazon River
      Delta, Para State, Brazil. The prevalence in fish (total body length 9-24 cm)
      examined from March 2009 to June 2010 (n=53) was 37%, with an intensity of 4-45
      (mean 14+/-11) larvae per fish. The nematode larvae (body length 16.2-21.6mm),
      characterized by the cephalic end provided with a helmet-like cuticular structure
      having a thickened free posterior margin, were studied based on light and
      scanning electron microscopy. Fish play a role of paratenic hosts for this
      nematode species. This is the first record of a larval nematode of the genus
      Pseudoproleptus from fish, and the second record of a larval nematode belonging
      to Cystidicolidae in the Amazon and in the Neotropics. Additional larval
      specimens were found free in the stomach of only 0.9% Ageneiosus ucayalensis
      Castelnau (Auchenipteridae) examined (n=205). This finding can be considered as
      occasional parasitism.

PMID- 21187055
TI  - A high-throughput matrix-assisted laser desorption/ionization-time-of-flight mass
      spectrometry-based assay of chitinase activity.
AB  - A high-throughput matrix-assisted laser desorption/ionization-time-of-flight mass
      spectrometry (MALDI-TOF MS) assay is described for determination of chitolytic
      enzyme activity. The assay uses unmodified chitin oligosaccharide substrates and
      is readily achievable on a microliter scale (2MUl of total volume containing 2MUg
      of substrate and 1ng of protein). The speed and sensitivity of the assay make it
      potentially well suited for the high-throughput screening of chitinase
      inhibitors. The mass spectrum is acquired in approximately 2min, as opposed to
      typically 30-40min for a single run with a high-performance liquid chromatography
      (HPLC)-based assay. By using the multiple-place MALDI MS targets, we estimate
      that 100 assays could be run in approximately 2-3h without needing to remove the
      target from the instrument. In addition, because the substrate and product
      chitomers are visualized simultaneously in the TOF spectrum, this gives immediate
      information about the cleavage site and mechanism of the enzyme under study. The
      assay was used to monitor the purification and transgenic expression of plant
      class IV chitinases. By performing the assay with chitomer substrates and C
      glycoside chitomer analogs, the enzyme mechanism of the class IV chitinases is
      described for the first time.

PMID- 21187056
TI  - Evaluation on the use of reactive dye-modified polylysine as the biomarker in
      immunochromatographic test application.
AB  - An improved dye immunochromatographic test (DICT) using polylysine (PL) as
      conjugate spacer loading dye molecules to enhance chromophor color intensity with
      the potential of a simultaneous multicolored assay has been developed. To
      construct this new effective chromophor, a dyeing process coupling a reactive
      dye, Procion Blue MX-7RX (PB7RX), with PL of different molecular weights was
      performed. The optimal conjugate condition between PB7RX and PL was studied. It
      showed that under the optimized dyeing conditions, a PL molecular weight of 189.4
      kDa and a molar ratio (mol dye/mol amine group in PL) of 1.5 were obtained. The
      resulting dyed PL chromophor, used as both a spacer and a color intensifier, was
      further labeled to a model antibody, anti-human serum albumin (anti-HSA), to
      build a PB7RX-PL-anti-HSA (PPA) conjugate. The PPA obtained in this way generated
      the highest color intensity of 19,455 assayed by immunochromatographic test strip
      under densitometer scanning. A competitive DICT for determination of HSA was
      carried out. A linear range between 0 and 18.77 MUg/ml with a detection limit of
      0.49 MUg/ml was observed. A test for using dyed PL chromophors as biomarkers was
      also performed to demonstrate the feasibility of a multianalyte immunoassay.

PMID- 21187057
TI  - Role of beta-TrCP ubiquitin ligase receptor in UVB mediated responses in skin.
AB  - Skin cancers are the most common cancers in the United States. Exposure to UVB
      radiation is a major risk factor for skin cancer induction. SCF(beta-TrCP) E3
      ubiquitin ligase has been found to be involved in cell cycle, cell proliferation
      and transformation. Aberrant up-regulation of beta-transducin repeats-containing
      proteins (beta-TrCP) is often found in cancer cell lines and primary tumors. We
      have previously demonstrated that beta-TrCP2 is over-expressed in chemically
      induced mouse skin tumors. Various cellular stress stimuli, including UVB, induce
      an increase in beta-TrCP1 mRNA and protein levels in human cells. We have
      previously shown that inhibition of beta-TrCP function, by induction of dominant
      negative beta-TrCP2 (beta-TrCP2(DeltaF)), in vitro in hTERT immortalized normal
      keratinocytes, results in increase in UVB induced apoptosis. We have generated
      transgenic mice with inducible, selective expression of dominant negative beta
      TrCP2 in epidermis with the Keratin 5 promoter (K5-rTA x TRE-HA-beta
      TrCP(DeltaF)). Here we report that inhibition of beta-TrCP function in mouse
      epidermis results in decrease in UVB-induced edema, hyperplasia, and inflammatory
      response and increment in UVB-induced apoptosis in skin. Our results suggest that
      beta-TrCP may be an essential player in UVB induced responses in skin and can be
      a potential therapeutic target for skin cancer.

PMID- 21187058
TI  - Evidence for amylase release by cyclin-dependent kinase 5 in the rat parotid.
AB  - Cyclin-dependent kinase 5 (Cdk5) plays no apparent role in cell cycle regulation,
      and Cdk5 is not activated by cyclins but only p35 or p39. Although the enzymatic
      activity of Cdk5 is highest in the central nervous system, recent reports
      indicate that it also has important functions in non-neuronal cells. In the
      present study, we investigated whether Cdk5 and its activators are expressed in
      rat parotid acinar cells, whether a beta-adrenergic agonist enhances the
      expression of Cdk5, and whether Cdk5 mediates amylase release. We found that Cdk5
      and its activator, cyclin I, were expressed in rat parotid acinar cells, and that
      the expression of Cdk5 was enhanced by treatment of the cells with isoproterenol.
      Amylase release stimulated by isoproterenol was depressed by the addition of
      olomoucine, a Cdk5 inhibitor, or by the introduction of an anti-Cdk5 antibody.
      Cdk5 activity was enhanced by treatment with isoproterenol and this enhanced
      activity was attenuated by the addition of olomoucine. Olomoucine also attenuated
      both phosphorylation of Munc18c and translocation of Munc18c from the plasma
      membrane induced by isoproterenol. These results indicated that beta-stimulation
      of rat parotid acinar cells enhanced the expression of Cdk5, and that this Cdk5
      activation may mediate amylase release through phosphorylation of Munc18c.

PMID- 21187060
TI  - Taurine bromamine: a potent oxidant of tryptophan residues in albumin.
AB  - Taurine is the most abundant free amino acid in leukocytes and can react with
      HOBr to produce taurine bromamine (Tau-NHBr). The aim of this study was to assess
      the ability of Tau-NHBr to oxidize tryptophan, either free or as a residue in
      albumin. We have demonstrated that Tau-NHBr is a powerful oxidant for tryptophan.
      Importantly, in comparison to taurine chloramine, HOCl or HOBr, Tau-NHBr exhibits
      a degree of selectivity for tryptophan. Oxidation of albumin by Tau-NHBr resulted
      in emission of light, and the quantum yield was more than 10-fold more efficient
      than that of the other oxidants. The fluorescence band corresponding to oxidized
      albumin (lambda(ex) 350/lambda(em) 450), which is characteristic of the formation
      of formylkynurenine, was significantly higher in reactions using Tau-NHBr.
      Excitation of the fluorescent probe 8-anilino-1-naphthalenesulfonate at 295 nm
      was used to assess the depletion of tryptophan residues in albumin. Results from
      this experiment further supported a higher efficiency of oxidation of tryptophan
      residues by Tau-NHBr. Other parameters of protein oxidation, including cysteine
      depletion and formation of carbonyl groups, were not significantly different
      between the oxidants tested. In conclusion, these results indicate that Tau-NHBr
      has a higher affinity for tryptophan residues in proteins.

PMID- 21187059
TI  - Substrate inhibition in human hydroxysteroid sulfotransferase SULT2A1: studies on
      the formation of catalytically non-productive enzyme complexes.
AB  - The cytosolic sulfotransferase hSULT2A1 is the major hydroxysteroid (alcohol)
      sulfotransferase in human liver, and it catalyzes the 3'-phosphoadenosine-5'
      phosphosulfate (PAPS)-dependent sulfation of various endogenous hydroxysteroids
      as well as many xenobiotics that contain alcohol and phenol functional groups.
      The hSULT2A1 often displays substrate inhibition, and we have hypothesized that a
      key element in this response to increasing substrate concentration is the
      formation of non-productive ternary dead-end enzyme complexes involving the
      nucleotide product, adenosine 3',5'-diphosphate (PAP). One of these substrates
      for hSULT2A1 is dehydroepiandrosterone (DHEA), a major circulating steroid
      hormone in humans that serves as precursor to both androgens and estrogens. We
      have utilized DHEA in both initial velocity studies and equilibrium binding
      experiments in order to evaluate the potential role of ternary complexes in
      substrate inhibition of the enzyme. Our results indicate that hSULT2A1 forms non
      productive ternary complexes that involve either DHEA or dehydroepiandrosterone
      sulfate, and the formation of these ternary complexes displays negative
      cooperativity in the binding of DHEA.

PMID- 21187061
TI  - Rare sugar D-psicose improves insulin sensitivity and glucose tolerance in type 2
      diabetes Otsuka Long-Evans Tokushima Fatty (OLETF) rats.
AB  - A rare sugar, D-psicose has progressively been evaluated as a unique metabolic
      regulator of glucose and lipid metabolism, and thus represents a promising
      compound for the treatment of type 2 diabetes mellitus (T2DM). The present study
      was undertaken to examine the underlying effector organs of D-psicose in lowering
      blood glucose and abdominal fat by exploiting a T2DM rat model, Otsuka Long-Evans
      Tokushima Fatty (OLETF) rats. Rats were fed 5% D-psicose or 5% D-glucose
      supplemented in drinking water, and only water in the control for 13 weeks and
      the protective effects were compared. A non-diabetic Long-Evans Tokushima Otsuka
      (LETO), fed with water served as a counter control of OLETF. After 13 weeks
      feeding, D-psicose treatment significantly reduced the increase in body weight
      and abdominal fat mass. Oral glucose tolerance test (OGTT) showed the reduced
      blood glucose and insulin levels suggesting the improvement of insulin resistance
      in OLETF rats. Oil-red-O staining elucidated that D-psicose significantly reduced
      lipid accumulation in the liver. Immunohistochemical analysis showed D-psicose
      induced glucokinase translocation from nucleus to cytoplasm of the liver which
      enhances glucokinase activity and subsequent synthesis of glycogen in the liver.
      D-psicose also protected the pathological change of the beta-cells of pancreatic
      islets. These data demonstrate that D-psicose controls blood glucose levels by
      reducing lipotoxicity in liver and by preserving pancreatic beta-cell function.

PMID- 21187062
TI  - ARP101, a selective MMP-2 inhibitor, induces autophagy-associated cell death in
      cancer cells.
AB  - Autophagy is a catabolic cellular process involving self-digestion and turnover
      of macromolecules and entire organelles. Autophagy is primarily a protective
      process in response to cellular stress, but it can be associated with cell death.
      Genetic evidence also supports autophagy function as a tumor suppressor
      mechanism. To identify specific regulators to autophagy, we screened the Lopac
      1280 and the Prestwick chemical libraries using a cell-based screening system
      with autophagy marker (green fluorescence protein conjugated LC3 protein (GFP
      LC3)). We identified ARP101, a selective matrix metalloproteinase-2 (MMP-2)
      inhibitor as one of the most potent inducer of autophagy. ARP101 treatment was
      highly effective in inducing the formation of autophagosome and conversion of
      LC3I into LC3II. Moreover, ARP101-induced autophagy was completely blocked in
      mouse embryo fibroblasts that lacked autophagy related gene 5 (ATG5(-/-) MEF).
      Interestingly, cell death induced by ARP101 was not inhibited by zVAD, a pan
      caspase inhibitor, whereas, it was efficiently suppressed by addition of 3
      methyladenine, an autophagy inhibitor. These results suggest that the selective
      MMP-2 inhibitor, ARP101, induces autophagy and autophagy-associated cell death.

PMID- 21187063
TI  - Isoforms of apolipoprotein C-I associated with individuals with coronary artery
      disease.
AB  - Apolipoprotein C-I (apoC-I) is a 6.6kDa serum protein associated with high
      density lipoproteins (HDL) and triglyceride-rich lipoproteins. In this study,
      apoC-I was examined in high density lipoprotein subfractions from individuals
      with and without coronary artery disease (CAD). New isoforms of apoC-I, were
      detected in the cohort of individuals with CAD using mass spectrometry while the
      expected apoC-I isoforms were absent. In addition, the apoC-I mass spectra for
      the CAD cohort had satellite peaks indicative of the involvement of oxidative
      processes. Further analysis of the mass spectra of the CAD and non-CAD cohorts
      suggest that the origin of these new isoforms may be due to genetic mutations
      that could compromise the function of apoC-I.

PMID- 21187064
TI  - Rapamycin treatment causes developmental delay, pigmentation defects, and
      gastrointestinal malformation on Xenopus embryogenesis.
AB  - Rapamycin is a drug working as an inhibitor of the TOR (target of rapamycin)
      signaling pathway and influences various life phenomena such as cell growth,
      proliferation, and life span extension in eukaryote. However, the extent to which
      rapamycin controls early developmental events of amphibians remains to be
      understood. Here we report an examination of rapamycin effects during Xenopus
      early development, followed by a confirmation of suppression of TOR downstream
      kinase S6K by rapamycin treatment. First, we found that developmental speed was
      declined in dose-dependent manner of rapamycin. Second, black pigment spots
      located at dorsal and lateral skin in tadpoles were reduced by rapamycin
      treatment. Moreover, in tadpole stages severe gastrointestinal malformations were
      observed in rapamycin-treated embryos. Taken together with these results, we
      conclude that treatment of the drug rapamycin causes enormous influences on early
      developmental period.

PMID- 21187065
TI  - Upregulation of mammary gland OCTNs maintains carnitine homeostasis in suckling
      infants.
AB  - BACKGROUND: Transport of L-carnitine, essential cofactor of fatty acid
      metabolism, into breast milk is critical for the normal growth and development of
      the suckling infant. OBJECTIVE: To increase understanding of developmental
      expression of carnitine/organic cation (Octn) transporter family at different
      stages of murine breast development for carnitine delivery. METHODS: We applied
      our transporter-specific antibodies to mOctn1, mOctn2 and mOctn3 to sections of
      mammary glands of virginal non-lactating, pregnant, late lactating and post
      lactating C3H females. RESULTS: We demonstrated differential expression of
      mOctn1, -2 and -3 in epithelial ducts, specialized myoepithelial cells and fatty
      stroma. There was notable upregulation of all three Octns and mRNA by RT-PCR
      concurrent with an increase in epithelial ducts in breasts of pregnant (15days
      gestation) and lactating mice (15-days post-partum) compared to virginal 6 week
      old females, and notable downregulation in expression of Octns 15 days after
      cessation of lactation. In lactating murine mammary gland at 15 days post-partum,
      there was a marked increase of fat globules in epithelial ducts. Octn1 and Octn2
      had similar expression patterns in lactating gland cells which formed fat
      globules that were exocytosed into the lumen of alveoli along with transporters
      Octn1 and Octn2. Octn3 was primarily localized to myoepithelial cells surrounding
      the ducts at all stages of breast development. CONCLUSIONS: There is a dynamic
      upregulation of the Octn family in pregnant and lactating breasts which likely
      provides the suckling infant with adequate carnitine for the rapid postnatal
      upregulation of fatty acid oxidation and ketogenesis critical for cerebral energy
      metabolism during fasting hypoglycemia.

PMID- 21187066
TI  - NF-kappaB suppresses HIF-1alpha response by competing for P300 binding.
AB  - Hypoxia has emerged as a key determinant of osteogenesis. HIF-1alpha is the
      transcription factor mediating hypoxia responses that include induction of VEGF
      and related bone induction. Inflammatory signals antagonize bone repair via the
      NF-kappaB pathway. The present investigation explored the functional relationship
      of hypoxia (HIF-1alpha function) and inflammatory signaling (NF-kappaB) in stem
      like and osteoprogenitor cell lines. The potential interaction between HIF-1alpha
      and NF-kappaB signaling was explored by co-transfection studies in hFOB with p65,
      HIF-1alpha and 9x-HRE-luc or HIF-1alpha target genes reporter plasmids. Nuclear
      cross-talk was directly tested using the mammalian Gal4/VP16 two-hybrid, and
      confirmed by co-immunoprecipitation/western blotting assays. The results show
      that inflammatory stimulation (TNF-alpha treatment) causes a marked inhibition of
      HIF-1alpha function at the HRE in all cell lines studied. Also, co-transfection
      with p65 expression vector leads to reduced hVEGFp transcription after DFO
      induced hypoxia. However, TNF-alpha treatment had little effect on HIF-1alpha
      mRNA levels. The functional interaction of Gal4-HIF-1alpha and VP16-p300 fusion
      proteins is effectively blocked by expression of p65 in a dose dependent manner.
      It was concluded that NF-kappaB-mediated inflammatory signaling is able to block
      HIF-1alpha transactivation at HRE-encoding genes by direct competition for p300
      binding at the promoter. Inflammation may influence the stem cell niche and
      tissue regeneration by influencing cellular responses to hypoxia.

PMID- 21187067
TI  - TLS and PRMT1 synergistically coactivate transcription at the survivin promoter
      through TLS arginine methylation.
AB  - TLS (Translocated in LipoSarcoma), also termed FUS, is a multifunctional protein
      implicated in diverse cellular events such as maintaining genome integrity and
      regulating gene expression. We have focused on the role of TLS as a coregulator
      in transcriptional regulation. In the process of investigating TLS-binding
      proteins, we found that PRMT1 (protein arginine methyltransferase 1) was in
      complex with TLS. We analyzed the methylation status of endogenous TLS and
      demonstrated that TLS was arginine-methylated by PRMT1. Using mass spectrometry,
      we identified that four arginine residues within TLS (R216, R218, R242 and R394)
      were consistently dimethylated. We performed luciferase reporter assays to assess
      the functional consequence of TLS arginine methylation in transcriptional
      regulation and, interestingly, observed that TLS and PRMT1 synergistically
      coactivated transcription at the survivin promoter. Further analysis using a
      catalytic-dead PRMT1 or methylation inhibitor both showed that the synergistic
      transcriptional activation was mediated by TLS arginine-methylation. These
      results revealed a cooperative role of TLS and PRMT1 in transcriptional
      regulation.

PMID- 21187069
TI  - Mitochondrial mass is inversely correlated to complete lipid oxidation in human
      myotubes.
AB  - Exercise increases while physical inactivity decrease mitochondrial content and
      oxidative capacity of skeletal muscles in vivo. It is unknown whether
      mitochondrial mass and substrate oxidation are related in non-contracting
      skeletal muscle. Mitochondrial mass, ATP, ADP, AMP, glucose and lipid oxidation
      (complete and incomplete) were determined in non-contracting myotubes established
      from 10 lean, 10 obese and 10 subjects with type 2 diabetes precultured under
      normophysiological conditions. ATP, ADP, AMP, mitochondrial mass and energy
      charge were not different between groups. In diabetic myotubes, basal glucose
      oxidation and incomplete lipid oxidation were significantly increased while
      complete lipid oxidation was lower. Mitochondrial mass was not correlated to
      glucose oxidation or incomplete lipid oxidation in human myotubes but inversely
      correlated to complete lipid oxidation. Thus within a stable energetic
      background, an increased mitochondrial mass in human myotubes was not positive
      correlated to an increased substrate oxidation as expected from skeletal muscles
      in vivo but surprisingly with a reduced complete lipid oxidation.

PMID- 21187068
TI  - Concerted actions of NHERF2 and WNK4 in regulating TRPV5.
AB  - With-no-lysine (K) kinase 4 (WNK4) is a protein serine/threonine kinase
      associated with a Mendelian form of hypertension. WNK4 is an integrative
      regulator of renal transport of Na(+), K(+), and Cl(-) as shown in Xenopus oocyte
      system. In addition, WNK4 enhances the surface expression of epithelial Ca(2+)
      channel TRPV5, which plays a key role in the fine tuning of renal Ca(2+)
      reabsorption. Variations in the magnitude of WNK4-mediated regulation on TRPV5 in
      Xenopus oocytes suggest additional cellular components with limited expression
      are required for the regulation. In this study, we identified the Na(+)/H(+)
      exchanger regulating factor 2 (NHERF2) as a critical component for the positive
      regulation of TRPV5 by WNK4. NHERF2 augmented the positive effect of WNK4 on
      TRPV5, whereas its homolog NHERF1 had no effect when tested in the Xenopus oocyte
      system. The C-terminal PDZ binding motif of TRPV5 was required for the regulation
      by NHERF2. While NHERF2 interacted with TRPV5, no association between NHERF2 and
      WNK4 was detected using a GST pull-down assay. WNK4 increased the forward
      trafficking of TRPV5; however, it also caused an accelerated decline of the
      functional TRPV5 channels at later stage of co-expression. NHERF2 stabilized
      TRPV5 at the plasma membrane without interrupting the forward trafficking of
      TRPV5, thus prevented the decline of functional TRPV5 channel caused by WNK4 at
      later stage. The complementary and orderly regulations of WNK4 and NHERF2 allow
      TRPV5 functions at higher level for a longer period to maximize Ca(2+) influx.

PMID- 21187070
TI  - The histone methyltransferase Dot1 is required for DNA damage repair and proper
      development in Dictyostelium.
AB  - Posttranslational histone modifications play an important role in modulating gene
      expression and chromatin structure. Here we report the identification of histone
      H3K79 dimethylation in the simple eukaryote Dictyostelium discoideum. We have
      deleted the D. discoideum Dot1/KMT4 homologue and demonstrate that it is the sole
      enzyme responsible for histone H3K79me2. Cells lacking Dot1 are reduced in growth
      and delayed in development, but do not show apparent changes in cell cycle
      regulation. Furthermore, our results indicate that Dot1 contributes to UV damage
      resistance and DNA repair in D. discoideum. In summary, the data support the view
      that the machinery controlling the setting of histone marks is evolutionary
      highly conserved and provide evidence that D. discoideum is a suitable model
      system to analyze these modifications and their functions during development and
      differentiation.

PMID- 21187071
TI  - AMP-activated protein kinase (AMPK) positively regulates osteoblast
      differentiation via induction of Dlx5-dependent Runx2 expression in MC3T3E1
      cells.
AB  - This study examined the role of AMPK activation in osteoblast differentiation and
      the underlining mechanism. An AMPK activator (AICAR or metformin) stimulated
      osteoblast differentiation with increases in ALP and OC protein production as
      well as the induction of AMPK phosphorylation in MC3T3E1 cells. In addition,
      metformin induced the phosphorylation of Smad1/5/8 and expression of Dlx5 and
      Runx2, whereas compound C or dominant negative AMPK inhibited these effects.
      Transient transfection studies also showed that metformin increased the BRE-Luc
      and Runx2-Luc activities, which were inhibited by DN-AMPK or compound C. Down
      regulation of Dlx5 expression by siRNA suppressed metformin-induced Runx2
      expression. These results suggest that the activation of AMPK stimulates
      osteoblast differentiation via the regulation of Smad1/5/8-Dlx5-Runx2 signaling
      pathway.

PMID- 21187072
TI  - Hyper-mobility of water around actin filaments revealed using pulse-field
      gradient spin-echo 1H NMR and fluorescence spectroscopy.
AB  - This paper reports that water molecules around F-actin, a polymerized form of
      actin, are more mobile than those around G-actin or in bulk water. A measurement
      using pulse-field gradient spin-echo (1)H NMR showed that the self-diffusion
      coefficient of water in aqueous F-actin solution increased with actin
      concentration by ~5%, whereas that in G-actin solution was close to that of pure
      water. This indicates that an F-actin/water interaction is responsible for the
      high self-diffusion of water. The local viscosity around actin was also
      investigated by fluorescence measurements of Cy3, a fluorescent dye, conjugated
      to Cys 374 of actin. The steady-state fluorescence anisotropy of Cy3 attached to
      F-actin was 0.270, which was lower than that for G-actin, 0.334. Taking into
      account the fluorescence lifetimes of the Cy3 bound to actin, their rotational
      correlation times were estimated to be 3.8 and 9.1ns for F- and G-actin,
      respectively. This indicates that Cy3 bound to F-actin rotates more freely than
      that bound to G-actin, and therefore the local water viscosity is lower around F
      actin than around G-actin.

PMID- 21187073
TI  - Characterization of sarcoplasmic reticulum Ca2+ ATPase nucleotide binding domain
      mutants using NMR spectroscopy.
AB  - Sarcoplasmic reticulum Ca(2+) ATPase (SERCA) is essential for muscle function by
      transporting Ca(2+) from the cytosol into the sarcoplasmic reticulum through ATP
      hydrolysis. In this report, the effects of substitution mutations on the isolated
      SERCA-nucleotide binding domain (SERCA-N) were studied using NMR. (15)N-(1)H HSQC
      spectra of substitution mutants at the nucleotide binding site, T441A, R560V, and
      C561A, showed chemical shift changes, primarily in residues adjacent to the
      mutation sites, indicating only local effects. Further, the patterns of chemical
      shift changes upon AMP-PNP binding to these mutants were similar to that of the
      wild type SERCA-N (WT). In contrast to these nucleotide binding site mutants, a
      mutant found in patients with Darier's disease, E412G, showed small but
      significant chemical shift changes throughout the protein and rapid
      precipitation. However, the AMP-PNP dissociation constant (~2.5 mM) was similar
      to that of WT (~3.8 mM). These results indicate that the E412G mutant retains its
      catalytic activity but most likely reduces its stability. Our findings provide
      molecular insight into previous clinical, physiological, and biochemical
      observations.

PMID- 21187074
TI  - Brain infarction correlates more closely with acrolein than with reactive oxygen
      species.
AB  - Although it is thought that the major factor responsible for cell damage is
      reactive oxygen species (ROS), our recent studies have shown that acrolein is
      more toxic than ROS. Thus, the relative importance of acrolein and ROS in cell
      damage during brain infarction was compared using photochemically induced
      thrombosis model mice. The levels of acrolein-conjugated albumin, and of 4
      hydroxynonenal (HNE)-conjugated albumin and 8-OHdG were evaluated as indicators
      of damage produced by acrolein and ROS, respectively. The increase in acrolein
      conjugated albumin was much greater than the increase in HNE-conjugated albumin
      or 8-OHdG, suggesting that acrolein is more strongly involved in cell damage than
      ROS during brain infarction. It was also shown that infarction led more readily
      to RNA damage than to DNA or phospholipid damage. As a consequence, polyamines
      were released from RNA, and acrolein was produced from polyamines, especially
      from spermine by spermine oxidase. Production of acrolein from spermine by
      spermine oxidase was clarified using spermine synthase-deficient Gy mice and
      transglutaminase 2-knockout mice, in which spermine content is negligible or
      spermidine/spermine N(1)-acetyltransferase activity is elevated.

PMID- 21187075
TI  - A novel binding protein of single immunoglobulin IL-1 receptor-related molecule:
      Paralemmin-3.
AB  - Previous studies have shown that single immunoglobulin IL-1 receptor-related
      molecule (SIGIRR) is a negative regulator of Toll-Interleukin-1 receptor
      signaling. Nevertheless, the molecular mechanism of the negatively regulatory
      effect of SIGIRR remains unknown. Using a yeast two-hybrid screen, we identified
      paralemmin-3 (PALM3) as a novel binding protein of SIGIRR. This interaction of
      SIGIRR with PALM3 was confirmed by coimmunoprecipitation in mammalian cells. In
      addition, the PALM3 mRNA expression was upregulated by lipopolysaccharide (LPS)
      stimulation in a human alveolar epithelial cell line (A549 cells). Furthermore,
      silencing PALM3 by RNA interference inhibited the release of inflammatory
      cytokines in A549 cells after LPS-stimulation. These results suggest that PALM3
      may function as an adaptor in the LPS- Toll-like receptor 4 signaling and the
      interaction of SIGIRR with PALM3 may partly account for the mechanism of the
      negatively regulatory effect of SIGIRR.

PMID- 21187076
TI  - Solution structure of Rap1 BRCT domain from Saccharomyces cerevisiae reveals a
      novel fold.
AB  - Rap1 (repressor-activator protein 1) from Saccharomyces cerevisiae, containing a
      BRCT domain at its N-terminus, is a multifunctional protein that controls
      telomere function, silencing, and the activation of glycolytic and ribosomal
      protein genes. In this work, we determined the solution structure of Rap1 BRCT
      domain, which contains three beta-strands and three alpha-helices. Structural
      comparison indicated that Rap1 BRCT domain adopts a global fold similar to other
      BRCT domains, implying some common structural aspects of BRCT domain family. On
      the other hand, Rap1 BRCT domain displays structural characteristics
      significantly different from other BRCT domains in that Rap1 BRCT domain adopts a
      rather flexible conformation with less secondary structure elements, revealing a
      novel fold of the BRCT domain family.

PMID- 21187077
TI  - Use of domain enzymes from wheat RNA ligase for in vitro preparation of RNA
      molecules.
AB  - Wheat RNA ligase can be dissected into three isolated domain enzymes that are
      responsible for its core ligase, 5'-kinase, and 2',3'-cyclic phosphate 3'
      phosphodiesterase activities, respectively. In the present study, we pursued a
      practical strategy using the domain enzymes for in vitro step-by-step ligation of
      RNA molecules. As a part of it, we demonstrated that a novel side reaction on 5'
      tri/diphosphate RNAs is dependent on ATP, a 2'-phosphate-3'-hydroxyl end, and the
      ligase domain. Mass spectroscopy and RNA cleavage analyses strongly suggested
      that it is an adenylylation on the 5' terminus. The ligase domain enzyme showed a
      high productivity for any of the possible 16 combinations of terminal bases and a
      high selectivity for the 5'-phosphate and 2'-phosphate-3'-hydroxyl ends. Two RNA
      molecules having 5'-hydroxyl and 2',3'-cyclic monophosphate groups were ligated
      almost stoichiometrically after separate conversion of respective terminal
      phosphate states into reactive ones. As the product has the same terminal state
      as the starting material, the next rounds of ligation are also possible in
      principle. Thus, we propose a flexible method for in vitro RNA ligation.

PMID- 21187078
TI  - Solution structure of UIM and interaction of tandem ubiquitin binding domains in
      STAM1 with ubiquitin.
AB  - STAM1 and Hrs are the components of ESCRT-0 complex for lysosomal degradation of
      membrane proteins is composed of STAM1 Hrs and has multiple ubiquitin binding
      domains. Here, the solution structure of STAM1 UIM, one of the ubiquitin binding
      motif, was determined by NMR spectroscopy. The structure of UIM adopts an alpha
      helix with amphipathic nature. The central hydrophobic residues in UIM provides
      the binding surface for ubiquitin binding and are flanked with positively and
      negatively charged residues on both sides. The docking model of STAM1 UIM
      ubiquitin complex is suggested. In NMR and ITC experiments with the specifically
      designed mutant proteins, we investigated the ubiquitin interaction of tandem
      ubiquitin binding domains from STAM1. The ubiquitin binding affinity of the VHS
      domain and UIM in STAM1 was 52.4 and 94.9 MUM, and 1.5 and 2.2 fold increased,
      respectively, than the value obtained from the isolated domain or peptide. The
      binding affinities here would be more physiologically relevant and provide more
      precise understanding in ESCRT pathway of lysosomal degradation.

PMID- 21187080
TI  - Protective effect of rat aldo-keto reductase (AKR1C15) on endothelial cell damage
      elicited by 4-hydroxy-2-nonenal.
AB  - 4-Hydroxy-2-nonenal (HNE), a major reactive product of lipid peroxidation, is
      believed to play a central role in atherogenic actions triggered by oxidized
      lipoproteins. An aldo-keto reductase (AKR) 1C15 efficiently reduces HNE and is
      distributed in many rat tissues including endothelial cells. In this study, we
      investigated whether AKR1C15 acts as a protective factor against endothelial
      damage elicited by HNE and oxidized lipoproteins. Treatment of rat endothelial
      cells with HNE provoked apoptosis through reactive oxygen species (ROS)
      formation, mitochondrial dysfunction and caspase activation in the cells. AKR1C15
      converted HNE into less toxic 1,4-dihydroxy-2-nonene, and its overexpression
      markedly decreased the susceptibility of the cells to HNE. The forced expression
      of AKR1C15 also significantly suppressed the loss of cell viability caused by
      oxidized low-density lipoprotein and its lipidic fraction. Furthermore, the
      treatment of the cells with sublethal concentrations of HNE resulted in up
      regulation of AKR1C15, which was partially abrogated by the ROS inhibitors.
      Collectively, these data indicate an anti-atherogenic function of AKR1C15 through
      the protection of endothelial cells from damage elicited by toxic lipids such as
      HNE.

PMID- 21187081
TI  - Cyclooxygenase-2 in oncogenesis.
AB  - Compelling experimental and clinical evidence supports the notion that
      cyclooxygenase-2, the inducible isoform of cyclooxygenase, plays a crucial role
      in oncogenesis. Clinical and epidemiological data indicate that aberrant
      regulation of cyclooxygenase-2 in certain solid tumors and hematological
      malignancies is associated with adverse clinical outcome. Moreover, findings
      extrapolated from experimental studies in cultured tumor cells and animal tumor
      models indicate that cyclooxygenase-2 critically influences all stages of tumor
      development from tumor initiation to tumor progression. Cyclooxygenase-2 elicits
      cell-autonomous effects on tumor cells resulting in stimulation of growth,
      increased cell survival, enhanced tumor cell invasiveness, stimulation of
      neovascularization, and tumor evasion from the host immune system. Additionally,
      the oncogenic effects of cyclooxygenase-2 stem from its unique ability to impact
      tumor cell surroundings and create a proinflammatory environment conducive for
      tumor development, growth and progression. The initial enthusiasm generated by
      the availability of cyclooxygenase-2 selective inhibitors for cancer prevention
      and therapy has been lessened by the severe cardiovascular adverse side effects
      associated with their long-term use, as well as by the mixed results of recent
      clinical trials evaluating the efficacy of cyclooxygenase-2 inhibitors in
      adjuvant chemotherapy. Therefore, our ability to efficiently target the oncogenic
      effects of cyclooxygenase-2 for therapeutic and preventive purposes strictly
      depends on a better understanding of the spatial and temporal aspects of its
      activation in tumor cells along with a clearer elucidation of the signaling
      networks whereby cyclooxygenase-2 affects tumor cells and their interactions with
      the tumor microenvironment. This knowledge has the potential of leading to the
      identification of novel cyclooxygenase-2-dependent molecular and signaling
      networks that can be exploited to improve cancer prevention and therapy.

PMID- 21187079
TI  - Roles of rat and human aldo-keto reductases in metabolism of farnesol and
      geranylgeraniol.
AB  - Farnesol (FOH) and geranylgeraniol (GGOH) with multiple biological actions are
      produced from the mevalonate pathway, and catabolized into farnesoic acid and
      geranylgeranoic acid, respectively, via the aldehyde intermediates (farnesal and
      geranylgeranial). We investigated the intracellular distribution, sequences and
      properties of the oxidoreductases responsible for the metabolic steps in rat
      tissues. The oxidation of FOH and GGOH into their aldehyde intermediates were
      mainly mediated by alcohol dehydrogenases 1 (in the liver and colon) and 7 (in
      the stomach and lung), and the subsequent step into the carboxylic acids was
      catalyzed by a microsomal aldehyde dehydrogenase. In addition, high reductase
      activity catalyzing the aldehyde intermediates into FOH (or GGOH) was detected in
      the cytosols of the extra-hepatic tissues, where the major reductase was
      identified as aldo-keto reductase (AKR) 1C15. Human reductases with similar
      specificity were identified as AKR1B10 and AKR1C3, which most efficiently reduced
      farnesal and geranylgeranial among seven enzymes in the AKR1A-1C subfamilies. The
      overall metabolism from FOH to farnesoic acid in cultured cells was significantly
      decreased by overexpression of AKR1C15, and increased by addition of AKR1C3
      inhibitors, tolfenamic acid and R-flurbiprofen. Thus, AKRs (1C15 in rats, and
      1B10 and 1C3 in humans) may play an important role in controlling the
      bioavailability of FOH and GGOH.

PMID- 21187082
TI  - Inhibition of soluble epoxide hydrolase attenuates endothelial dysfunction in
      animal models of diabetes, obesity and hypertension.
AB  - Endothelial dysfunction is a hallmark of, and plays a pivotal role in the
      pathogenesis of cardiometabolic diseases, including type II diabetes, obesity,
      and hypertension. It has been well established that epoxyeicosatrienoic acids
      (EETs) act as an endothelial derived hyperpolarization factor (EDHF). Soluble
      epoxide hydrolase (s-EH) rapidly hydrolyses certain epoxylipids (e.g. EETs) to
      less bioactive diols (DHETs), thereby attenuating the evoked vasodilator effects.
      The aim of the present study was to examine if inhibition of s-EH can restore
      impaired endothelial function in three animal models of cardiometabolic diseases.
      Isolated vessel rings of the aorta and/or mesenteric artery from mice or rats
      were pre-contracted using phenylephrine or U46619. Endothelium-dependent and
      independent vasorelaxation to acetylcholine and sodium nitroprusside (SNP) were
      measured using wire myography in vessels isolated from db/db or diet-induced
      obesity (DIO) mice, and angiotensin II-induced hypertensive rats treated
      chronically with s-EH inhibitors AR9281 or AR9276 or with vehicle. Vasorelaxation
      to acetylcholine, but not to SNP was severely impaired in all three animal
      models. Oral administration of AR9281 or AR9276 abolished whole blood s-EH
      activity, elevated epoxy/diol lipid ratio, and abrogated endothelial dysfunction
      in all three models. Incubating the mesenteric artery of db/db mice with L-NAME
      and indomethacin to block nitric oxide (NO) and prostacyclin formation did not
      affect AR9821-induced improvement of endothelial function. These data indicate
      that inhibition of s-EH ameliorates endothelial dysfunction and that effects in
      the db/db model are independent of the presence of NO and cyclooxygenase derived
      prostanoids. Thus, preserving vasodilator EETs by inhibition of s-EH may be of
      therapeutic benefit by improving endothelial function in cardiometabolic
      diseases.

PMID- 21187083
TI  - Effects of fucoxanthin on proliferation and apoptosis in human gastric
      adenocarcinoma MGC-803 cells via JAK/STAT signal pathway.
AB  - In this study, we investigated the anti-tumor effects and possible mechanisms of
      fucoxanthin, which has been reported to inhibit tumor proliferation and induce
      apoptosis in vitro or in vivo. Human gastric adenocarcinoma MGC-803 cells were
      treated with fucoxanthin (25MUM, 50MUM or 75MUM). Data of flow cytometry revealed
      that fucoxanthin (50MUM or 75MUM) increased the ratio of cell in G2/M phase and
      apoptotic MGC-803 cells varying on a dose-dependent manner. Results from reverse
      transcriptase-polymerase chain reaction and Western blot showed that treatment
      with fucoxanthin (50MUM or 75MUM) significantly decreased the expressions of
      CyclinB1, survivin and STAT3 in MGC-803 cells in a dose-dependent manner both at
      the time of 24h and 48h. In addition, immunofluorescence microscopy analysis also
      revealed the suppressed expressions of CyclinB1 and survivin by fucoxanthin.
      After pretreatment with AG490 (the inhibitor for JAK/STAT signal pathway), the
      expressions of p-STAT3 and survivin remained also slightly lower than the vehicle
      control group. Co-treated with fucoxanthin (75MUM) and AG490, the reduction on
      the expressions of STAT3, p-STAT3 and CyclinB1 by fucoxanthin were attenuated
      while that of survivin was enhanced. Taken together, fucoxanthin can down
      regulate the expressions of CyclinB1 and survivin, inducing cell cycle arrest in
      G2/M phase, and apoptosis in MGC-803 cells. The reduction of CyclinB1 by
      fucoxanthin was associated with JAK/STAT signal pathway.

PMID- 21187084
TI  - Curcumin inhibits renal cyst formation and enlargement in vitro by regulating
      intracellular signaling pathways.
AB  - Autosomal dominant polycystic kidney disease, a common inherited disease
      affecting about 1/1000 and 1/400 live births, is characterized by massive
      enlargement of fluid-filled cysts and eventually causes renal failure. The
      purpose of this study is to identify the inhibitory effect of curcumin on renal
      cyst development and to investigate the inhibitory mechanism. Madin-Darby canine
      kidney (MDCK) cyst model and murine embryonic kidney cyst model were used to
      evaluate inhibitory activity. Cell viability, proliferation, apoptosis, CFTR
      function and expression, and signaling pathways in MDCK cells were determined to
      explore the mechanism of cyst inhibition. Curcumin was found to significantly
      inhibit MDCK cyst development. At maximum dose curcumin caused 62% inhibition of
      the cyst formation (IC(50) was 0.12 MUM). Curcumin slowed cyst enlargement in
      both MDCK cyst model and embryonic kidney cyst model with dose-response
      relationship. Curcumin neither induced cytotoxicity nor apoptosis in MDCK cells
      at <100 MUM. Curcumin failed to affect the chloride transporter CFTR expression
      and function. Interestingly, curcumin inhibited forskolin-promoted cell
      proliferation and promoted the tubule formation in MDCK cells, which indicates
      curcumin promotes MDCK cell differentiation. Furthermore, curcumin reduced the
      intracellular signaling proteins Ras, B-raf, p-MEK, p-ERK, c-fos, Egr-1, but
      increased Raf-1 and NAB2 in MDCK cells exposed to forskolin. These results define
      that curcumin inhibits renal cyst formation and enlargement and suggest that
      curcumin might be developed as a candidate drug for polycystic kidney disease.

PMID- 21187085
TI  - Imaging the aqueous humor outflow pathway in human eyes by three-dimensional
      micro-computed tomography (3D micro-CT).
AB  - The site of outflow resistance leading to elevated intraocular pressure in
      primary open-angle glaucoma is believed to be located in the region of Schlemm's
      canal inner wall endothelium, its basement membrane and the adjacent
      juxtacanalicular tissue. Evidence also suggests collector channels and
      intrascleral vessels may have a role in intraocular pressure in both normal and
      glaucoma eyes. Traditional imaging modalities limit the ability to view both
      proximal and distal portions of the trabecular outflow pathway as a single unit.
      In this study, we examined the effectiveness of three-dimensional micro-computed
      tomography (3D micro-CT) as a potential method to view the trabecular outflow
      pathway. Two normal human eyes were used: one immersion fixed in 4%
      paraformaldehyde and one with anterior chamber perfusion at 10 mmHg followed by
      perfusion fixation in 4% paraformaldehyde/2% glutaraldehyde. Both eyes were
      postfixed in 1% osmium tetroxide and scanned with 3D micro-CT at 2 MUm or 5 MUm
      voxel resolution. In the immersion fixed eye, 24 collector channels were
      identified with an average orifice size of 27.5 +/- 5 MUm. In comparison, the
      perfusion fixed eye had 29 collector channels with a mean orifice size of 40.5 +/
      13 MUm. Collector channels were not evenly dispersed around the circumference of
      the eye. There was no significant difference in the length of Schlemm's canal in
      the immersed versus the perfused eye (33.2 versus 35.1 mm). Structures, locations
      and size measurements identified by 3D micro-CT were confirmed by correlative
      light microscopy. These findings confirm 3D micro-CT can be used effectively for
      the non-invasive examination of the trabecular meshwork, Schlemm's canal,
      collector channels and intrascleral vasculature that comprise the distal outflow
      pathway. This imaging modality will be useful for non-invasive study of the role
      of the trabecular outflow pathway as a whole unit.

PMID- 21187086
TI  - Fluorescent Leishmania species: development of stable GFP expression and its
      application for in vitro and in vivo studies.
AB  - Reporter genes have proved to be an excellent tool for studying disease
      progression. Recently, the green fluorescent protein (GFP) ability to
      quantitatively monitor gene expression has been demonstrated in different
      organisms. This report describes the use of Leishmania tarentolae (L. tarentolae)
      expression system (LEXSY) for high and stable levels of GFP production in
      different Leishmania species including L. tarentolae, L. major and L. infantum.
      The DNA expression cassette (pLEXSY-EGFP) was integrated into the chromosomal ssu
      locus of Leishmania strains through homologous recombination. Fluorescent
      microscopic image showed that GFP transgenes can be abundantly and stably
      expressed in promastigote and amastigote stages of parasites. Furthermore, flow
      cytometry analysis indicated a clear quantitative distinction between wild type
      and transgenic Leishmania strains at both promastigote and amastigote forms. Our
      data showed that the footpad lesions with GFP-transfected L. major are
      progressive over time by using fluorescence small-animal imaging system.
      Consequently, the utilization of stable GFP-transfected Leishmania species will
      be appropriate for in vitro and in vivo screening of anti-leishmanial drugs and
      vaccine development as well as understanding the biology of the host-parasite
      interactions at the cellular level.

PMID- 21187087
TI  - Evaluation of DNA/DNA and prime-boost vaccination using LPG3 against Leishmania
      major infection in susceptible BALB/c mice and its antigenic properties in human
      leishmaniasis.
AB  - One of the main issues in vaccine development is implementation of new adjuvants
      to improve the antigen presentation and eliciting the protective immune response.
      Heat shock protein (HSP) molecules are known as natural adjuvants. They can
      stimulate the innate and adaptive immune response against infectious diseases and
      cancer. Lipophosphoglycan 3 (LPG3), the Leishmania homologous with GRP94 (glucose
      regulated protein 94), a member of HSP90 family, is involved in assembly of LPG
      as the most abundant macromolecule on the surface of Leishmania promastigotes. In
      the present study as a primary step, we tested LPG3 as a vaccine candidate in two
      regimens, DNA/DNA and prime-boost (DNA/Protein), against Leishmania major
      infection in BALB/c mice model. Our results showed that LPG3 and its fragment
      (rNT-LPG3) are highly immunogenic in BALB/c mice and can stimulate the production
      of both IgG1 and IgG2a. In prime-boost immunization strategy, the level of
      antibody response was higher compared with DNA/DNA immunization. The levels of
      IFN-gamma in the supernatant of splenocytes from mice immunized with DNA/DNA and
      prime-boost regimens were significantly higher when compared to control groups.
      In fact, immunization with prime-boost vaccination has higher ratio of IFN
      gamma/IL-5, suggesting a shift towards a Th1 response. In addition, sera
      reactivity against LPG3 in visceral leishmaniasis (VL) patients was significantly
      higher in comparison with cutaneous leishmaniasis (CL) patients. Therefore, we
      recommend further investigations on the usage of LPG3 co-delivery with candidate
      antigens for vaccine development against leishmaniasis.

PMID- 21187088
TI  - Anandamide inhibits oxidative phosphorylation in isolated liver mitochondria.
AB  - A study on the effect of anandamide (AEA) in energy coupling of rat liver
      mitochondria is presented. Micromolar concentrations of AEA, while almost
      ineffective on substrate supported oxygen consumption rate and on uncoupler
      stimulated respiration, strongly inhibited the respiratory state III. AEA did not
      change the rate and the extent of substrate generated membrane potential, but
      markedly delayed rebuilding by respiration of the potential collapsed by ADP
      addition. Overall, these data suggest that anandamide inhibits the oxidative
      phosphorylation process. Direct measurement of the F(o)F(1) ATP synthase activity
      showed that the oligomycin sensitive ATP synthesis was inhibited by AEA, (IC(50),
      2.5 MUM), while the ATP hydrolase activity was unaffected. Consistently, AEA did
      not change the membrane potential generated by ATP hydrolysis.

PMID- 21187089
TI  - Metallothionein-2A overexpression increases the expression of matrix
      metalloproteinase-9 and invasion of breast cancer cells.
AB  - The overexpression of metallothionein-2A (MT-2A) is frequently observed in
      invasive human breast tumors and has been linked with more aggressive breast
      cancers. MT-2A overexpression led to the induction of MDA-MB-231 breast cancer
      cell migratory and invasive abilities. The reduction of MT-2A expression through
      small interfering RNA (siRNA) targeting MT-2A in invasive MDA-MB-231 cells
      completely inhibited both cell invasion and migration. In addition, the
      expression of matrix metalloproteinase-9 (MMP-9) and the transcriptional activity
      of AP-1 and NF-kappaB were upregulated by MT-2A overexpression. Collectively, our
      results provide the first demonstration that MT-2A promotes breast cancer cell
      invasion by upregulating MMP-9 via AP-1 and NF-kappaB activation. Furthermore, we
      found that MT-2A silencing can inhibit breast cancer invasiveness.

PMID- 21187090
TI  - Nerve growth factor receptor TrkA exists as a preformed, yet inactive, dimer in
      living cells.
AB  - The tropomyosin-related kinase A (TrkA) receptor and its ligand, nerve growth
      factor (NGF), play crucial roles in the development and function of the nervous
      system. NGF is believed to activate TrkA by bridging two TrkA monomers, leading
      to TrkA transphosphorylation. However, here we show that the majority of TrkA
      receptors exist as preformed, yet inactive, homodimers prior to NGF binding by
      using three different approaches such as chemical crosslinking and enzyme
      fragment complementation assay. Furthermore, TrkA homodimers are formed in
      endoplasmic reticulum before newly synthesized receptors reach the cell surface.
      These findings shed light on molecular mechanisms underlying transmembrane
      signaling by TrkA.

PMID- 21187091
TI  - Establishment of interferon alpha-resistant hepatitis C virus using cell culture
      system.
AB  - To investigate the molecular mechanisms underlying interferon alpha (IFNalpha)
      treatment failure in hepatitis C virus (HCV) patients with chronic hepatitis, we
      aimed to develop an IFNalpha-resistant clone of HCV. By treating JFH-1-infected
      Huh7.5 cells with a prolonged low-dose treatment of IFNalpha, we selected a clone
      of HCV that survived against 100 U/ml of IFNalpha. By genetic analysis of this
      clone, we found four substitution mutations in the C-terminal coding sequence of
      non-structural 5A (NS5A). By introducing these four mutations into wild-type JFH
      1, we established a new HCV clone that acquired IFNalpha resistant phenotype.
      These data suggest that four amino acid substitutions in NS5A are involved in
      IFNalpha resistance and thus this newly established HCV may be a useful tool for
      elucidating the molecular mechanisms of IFNalpha resistance in HCV patients.

PMID- 21187092
TI  - Protein kinase CK2 associates to lipid rafts and its pharmacological inhibition
      enhances neurotransmitter release.
AB  - In the present work we report the presence of protein kinase CK2 in lipid raft
      preparations from rat brain synaptosomes, obtained after detergent extraction and
      subsequent isolation of detergent-resistant membranes using sucrose gradient
      ultracentrifugation. Moreover, the phosphorylation of syntaxin-1 at Ser14, a
      specific CK2 target, has been detected in lipid rafts, as assessed by a phospho
      specific antibody. Treatment with DMAT, a specific CK2 inhibitor, results in a
      decrease of syntaxin-1 Ser14 phosphorylation in lipid rafts, while the glutamate
      release from synaptosomes is enhanced. In conclusion, CK2 might control
      neurotransmitter release by acting on SNARE proteins attached to cholesterol
      enriched microdomains.

PMID- 21187093
TI  - Involvement of miR-21 in resistance to daunorubicin by regulating PTEN expression
      in the leukaemia K562 cell line.
AB  - Recent studies have shown microRNA-21 (miR-21) is overexpressed in several types
      of cancer and contributes to tumor resistance to chemotherapy. In this study, we
      investigated whether miR-21 mediated resistance of the leukaemia cell line K562
      to the chemotherapeutic agent daunorubicin (DNR). miR-21 expression was
      upregulated in the DNR resistant cell line K562/DNR compared to its parental line
      K562. Stable transfection of miR-21 induced drug resistance in K562, while
      suppression of miR-21 in K562/DNR led to enhanced DNR cytotoxicity. Additional
      experiments indicate that the mechanism of miR-21 drug resistance involves the
      PI3K/Akt pathway and changes following PTEN protein expression. This study
      provides a novel mechanism for understanding leukaemia drug resistance.

PMID- 21187094
TI  - Interaction of purified alternative oxidase from thermogenic Arum maculatum with
      pyruvate.
AB  - Plant alternative oxidase (AOX) activity in isolated mitochondria is regulated by
      carboxylic acids, but reaction and regulatory mechanisms remain unclear. We show
      that activity of AOX protein purified from thermogenic Arum maculatum spadices is
      sensitive to pyruvate and glyoxylate but not succinate. Rapid, irreversible AOX
      inactivation occurs in the absence of pyruvate, whether or not duroquinol
      oxidation has been initiated, and is insensitive to duroquinone. Our data
      indicate that pyruvate stabilises an active conformation of AOX, increasing the
      population of active protein in a manner independent of reducing substrate and
      product, and are thus consistent with an exclusive effect of pyruvate on the
      enzyme's apparent V(max).

PMID- 21187095
TI  - Over-expression of sly-miR156a in tomato results in multiple vegetative and
      reproductive trait alterations and partial phenocopy of the sft mutant.
AB  - Plant microRNAs (miRNAs) are vital components of the translation control system
      that regulates plant development and reproduction. The biological function of sly
      miR156 was investigated by over-expression in tomato plants. Transgenic tomato
      plants exhibited a drastically altered phenotype, with reduced height, smaller
      but more numerous leaves, and smaller fruit. The inflorescence structure of sly
      miR156 over-expressing plants phenocopied the sft mutant. The putative targets of
      sly-miR156 were identified by data base search and included six SQUAMOSA PROMOTER
      BINDING PROTEIN (SBP)-box transcription factor genes. Their expression patterns
      were then determined in 35S-miR156a and wild type tomato plants. These target
      genes, as well as the tomato FLOWERING LOCUS T (FT) ortholog SFT, were
      significantly down-regulated in sly-miR156 over-expressing plants. These studies
      reveal novel phenotypes regulated by miR156.

PMID- 21187096
TI  - Prolactin acts on the hypothalamic-pituitary axis to modulate follicle
      stimulating hormone gene expression in the female brushtail possum (Trichosurus
      vulpecula).
AB  - Brushtail possums exhibit a distinct preovulatory pattern of prolactin (Prl)
      secretion suggesting that Prl is involved in normal reproductive function. In
      some mammals, Prl is essential for corpus luteum (CL) function and/or modulation
      of steroidal effects on hypothalamic-pituitary activity. The aim of this study
      was to test the effects of biologically active recombinant possum Prl (recPosPrl)
      on both pituitary gland and CL function in possums. To confirm biological
      activity, administration of recPosPrl-N2C1 (10 MUg) resulted in an 18-fold
      stimulation (P<0.05) of progesterone (P(4)) production by possum granulosa cells
      in vitro. Based on these findings, minipumps containing either recPosPrl-N2C1
      (n=10) or saline (n=8) were inserted into lactating female possums. The
      expression levels of pituitary-derived PRL, LHB, FSHB and GNRHR and CL-derived
      LHR mRNA were quantified. Following a resumption of reproductive activity, no
      differences in ovulation incidence or plasma Prl concentrations were observed.
      Plasma Prl levels were less variable (P<0.001) in Prl-treated possums, confirming
      a self-regulatory role for Prl in this species. There was a marked down
      regulation (P<0.001) of FSHB mRNA at the mid-luteal stage in Prl-treated possums,
      whereas mean PRL, LHB, GNRHR and LHR mRNA expression levels were not different
      between experimental groups. Plasma P(4) concentrations were not different
      (P=0.05) in Prl-treated possums, although tended to be higher in the peri
      ovulatory and early-luteal phase. We conclude in the brushtail possum that Prl is
      self-regulated via a short-feedback loop common to all mammals studied and is
      able to modulate FSHB expression probably at the level of the hypothalamus and/or
      pituitary gland.

PMID- 21187097
TI  - Auto-regulation of thyroid hormone receptors in the goldfish ovary and testis.
AB  - Thyroid hormones, acting via their cognate thyroid receptors (TRs) act as
      mediators and modulators of several physiological processes and homeostasis. A
      clear role for the TRs in reproduction has not yet been established although
      several lines of recent evidence suggest that they are involved in the regulation
      of reproduction. To further study the role of TRs in control of reproduction, we
      investigated homologous regulation of TR subtypes in the gonads of goldfish, in
      vivo and in vitro. It was found that tri-iodothyronine (T(3)) down-regulates the
      traditional TRs (TRalpha-1 and TRbeta) and up-regulates a dominant-negative form,
      TRalpha-t. This indicates a 'feedback' mechanism whereby an acute treatment with
      T(3) down regulates further T(3) mediated response. The results provide novel
      information on auto-regulation of TRs in the goldfish ovary and testis, and
      support the hypothesis that thyroid hormones are involved in the control of
      reproduction.

PMID- 21187098
TI  - Energy homeostasis regulatory peptides in hibernating grizzly bears.
AB  - Grizzly bears (Ursus arctos horribilis) are inactive for up to 6 months during
      hibernation. They undergo profound seasonal changes in food intake, body mass,
      and energy expenditure. The circa-annual regulation of metabolism is poorly
      understood. In this study, we measured plasma ghrelin, leptin, obestatin, and
      neuropeptide-Y (NPY) levels, hormones known to be involved in the regulation of
      energy homeostasis, in ten grizzly bears. Blood samples were collected during the
      active summer period, early hibernation and late hibernation. Plasma levels of
      leptin, obestatin, and NPY did not change between the active and the hibernation
      periods. Plasma total ghrelin and desacyl-ghrelin concentrations significantly
      decreased during the inactive winter period compared to summer levels. The
      elevated ghrelin levels may help enhance body mass during pre-hibernation, while
      the low plasma ghrelin concentrations during hibernation season may contribute to
      the maintenance of hypophagia, low energy utilization and behavioral inactivity.
      Our results suggest that ghrelin plays a potential role in the regulation of
      metabolic changes and energy homeostasis during hibernation in grizzly bears.

PMID- 21187099
TI  - Follicle-stimulating hormone regulation of ovarian transcripts for
      steroidogenesis-related proteins and cell survival, growth and differentiation
      factors in vitro during early secondary oocyte growth in coho salmon.
AB  - Little is known about follicle-stimulating hormone (FSH) function during oocyte
      growth in fishes. The goal of this study was to gain a fundamental understanding
      of FSH action on ovarian follicles during early secondary oocyte growth by
      examining changes in ovarian gene expression and steroidogenesis in response to
      FSH. Coho salmon (Oncorhynchus kisutch) mid to late cortical alveolus stage
      follicles were incubated with or without salmon FSH in time-course and
      concentration-response experiments. Steroid levels were determined in the culture
      medium by immunoassay and levels of target ovarian mRNAs were determined by
      quantitative RT-PCR. Medium estradiol-17beta (E2) levels increased in response to
      FSH and plateaued by 36h, while testosterone levels increased similarly but were
      lower and more variable than E2. Gonadotropin receptor transcripts were
      differentially regulated, with fshr and lhcgr being down- and up- regulated,
      respectively. Transcripts encoding proteins involved in steroidogenesis, such as
      star and hsd3b were significantly upregulated by FSH, whereas aromatase
      (cyp19a1a) mRNA was unaffected by FSH and declined over time in culture. A
      recently identified teleost gene, bmp16, was suppressed by FSH and an anti
      apoptotic factor, clusterin 1 (clu1), was upregulated by FSH. Lesser FSH effects
      were observed on igf2, cyp11a1 and cyp17a1, which were stimulated, and igf1ra,
      inhbb, amh and apoe, which were suppressed. As evident by the significant
      increases in steroid production and transcripts for specific steroidogenesis
      related proteins, FSH influences steroidogenesis during early secondary growth
      and may be a critical signal for puberty onset. Effects of FSH on ovarian anti
      apoptotic and growth factor genes suggest roles for FSH in cell survival, growth
      and differentiation in teleosts.

PMID- 21187100
TI  - Feather follicles express two classes of pro-opiomelanocortin (POMC) mRNA using
      alternative promoters in chickens.
AB  - Feather coloration in chickens mainly depends on melanin produced by melanocytes
      located in the feather follicles. The melanocortin 1 receptor (MC1R) on
      follicular melanocytes regulates melanin synthesis; however, the source of the
      melanocortins that interact with the receptors remains unclear. In this study, we
      examine the potential expression of melanocortins and characterize the mRNAs for
      the precursor pro-opiomelanocortin (POMC) in chicken feather follicles. Reverse
      transcription-polymerase chain reaction (RT-PCR) revealed the expression of mRNAs
      for POMC, prohormone convertase 1 (PC1) and PC2, and western blotting detected
      adrenocorticotropic hormone (ACTH)-related products of POMC processing in feather
      follicles, suggesting that melanocortins are produced locally in the tissues of
      chickens. A combination of 5'RACE (rapid amplification of cDNA 5' end), 3'RACE
      and RT-PCR analyzes identified two classes of POMC mRNA, class a and class b,
      which encode the same full-length POMC protein but have different non-coding
      leader exons. Class a mRNAs were expressed specifically in feather follicles,
      whereas class b mRNAs were expressed in the pituitary, hypothalamus, and various
      peripheral tissues that we examined. Within the feather follicles, the class a
      mRNAs were distributed in epidermal layers from middle to distal locations,
      whereas the class b mRNAs were mainly expressed in pulp at proximal locations.
      Our findings suggest that feather pigmentation is regulated by locally produced
      melanocortins, and indicate that the melanocortins encoded by the different
      classes of POMC mRNAs may play different intra-follicular roles in chickens. This
      is the first report that demonstrates alternative promoter usage generating
      different full-length POMC mRNAs in vertebrates.

PMID- 21187101
TI  - TWIG: a model to simulate the gravitropic response of a tree axis in the frame of
      elasticity and viscoelasticity, at intra-annual time scale.
AB  - Trees are able to maintain or modify the orientation of their axes (trunks or
      branches) by tropic movements. For axes in which elongation is achieved but
      cambial growth active, the tropic movements are due to the production of a
      particular wood, called reaction wood which is prestressed within the growing
      tree. Several models have been developed to simulate the gravitropic response of
      axes in trees due to the formation of reaction wood, all within the frame of
      linear elasticity and considering the wood maturation as instantaneous. The
      effect viscoelasticity of wood has, to our knowledge, never been considered. The
      TWIG model presented in this paper aims at simulating the gravitropic movement of
      a tree axis at the intra-annual scale. In this work we studied both the effect of
      a non-instantaneous maturation process and of viscoelasticity. For this purpose,
      we considered the elastic case with maturation considered as an instantaneous
      process as the reference. The introduction of viscoelasticity in TWIG has been
      done by coupling TWIG to a model developed for bridges. Indeed from a purely
      mechanical point of view, bridges and trees are very similar: they are structures
      which are built in stages, they are made of several materials (composite
      structures), their materials are prestressed (wood is prestressed during the
      maturation process as a result of polymerisation of lignin and cellulose to form
      the secondary cell wall and concrete is prestressed during drying). Simulations
      gave evidence that the reorientation process of axes can be significantly
      influenced by the kinetics of maturation. Moreover the model has now to be tested
      with more experimental data of wood viscoelasticity but it appears that in the
      range of a relaxation time from 0 to 50 days, viscoelasticity has an important
      effect on the evolution of tree shape as well as on the values of prestresses.

PMID- 21187102
TI  - Mechanisms of vegetation-ring formation in water-limited systems.
AB  - A common patch form in dryland landscapes is the vegetation ring. Vegetation
      patch formation has recently been attributed to self-organization processes that
      act to increase the availability of water to vegetation patches under conditions
      of water scarcity. The view of ring formation as a water-limited process,
      however, has remained largely unexplored. Using laboratory experiments and model
      studies we identify two distinct mechanisms of ring formation. The first
      mechanism pertains to conditions of high infiltration contrast between vegetated
      and bare soil, under which overland water flow is intercepted at the patch
      periphery. The decreasing amount of water that the patch core receives as the
      patch expands, leads to central dieback and ring formation. The second mechanism
      pertains to plants with large lateral root zones, and involves central dieback
      and ring formation due to increasing water uptake by the newly recruited
      individuals at the patch periphery. In general the two mechanisms act in concert,
      but the relative importance of each mechanism depends on environmental
      conditions. We found that strong seasonal rainfall variability favors ring
      formation by the overland-flow mechanism, while a uniform rainfall regime favors
      ring formation by the water-uptake mechanism. Our results explain the formation
      of rings by fast-growing species with confined root zones in a dry-Mediterranean
      climate, such as Poa bulbosa. They also explain the formation of rings by slowly
      growing species with highly extended root zones, such as Larrea tridentata
      (Creosotebush).

PMID- 21187103
TI  - The impact of vaccine side effects on the natural history of immunization
      programmes: an imitation-game approach.
AB  - When the incidence and prevalence of most common vaccine preventable childhood
      infectious diseases are constantly low, as is the case in many industrialized
      countries, the incidence of vaccine-associated side effects might become a key
      determinant in vaccine demand. We study an SIR transmission model with dynamic
      vaccine demand based on an imitation mechanism where the perceived risk of
      vaccination is modelled as a function of the incidence of vaccine side effects.
      The model shows some important differences compared to previous game dynamic
      models of vaccination, and allows noteworthy inferences as regards both the past
      and future lifetime of vaccination programmes. In particular it is suggested that
      a huge disproportion between the perceived risk of disease and vaccination is
      necessary in order to achieve high coverages. This disproportion is further
      increased in highly industrialised countries. Such considerations represent
      serious challenges for future vaccination programmes.

PMID- 21187104
TI  - Ghrelin-induced activation of cAMP signal transduction and its negative
      regulation by endocannabinoids in the hippocampus.
AB  - Increasing evidence indicates that the gut peptide ghrelin facilitates learning
      behavior and memory tasks. The present study demonstrates a cellular signaling
      mechanism of ghrelin in the hippocampus. Ghrelin stimulated CREB (cAMP response
      element binding protein) through the activation of cAMP, protein kinase A (PKA),
      and PKA-dependent phosphorylation of NR1 subunit of the NMDA receptor. Ghrelin
      increased phalloidin-binding to F-actin suggesting CREB-induced gene expression
      might include reorganization of cytoskeletal proteins. The effect was blocked by
      the antagonist of the ghrelin receptor in spite of the receptor's primary
      coupling to Gq proteins. We also discovered inhibitory effect of endocannabinoids
      on ghrelin-induced NR1 phosphorylation and CREB activity. 2-arachidonoylglycerol
      (2-AG) exerted its inhibitory effect in the Type 1 cannabinoid receptor (CB1R)
      dependent manner, while anandamide's inhibitory effect persisted in the presence
      of antagonists of CB1R and the vanilloid receptor, suggesting that anandamide
      might directly inhibit NMDA receptor/channels. Our findings may explain how
      ghrelin and endocannabinoids regulate hippocampal appetitive learning and
      plasticity.

PMID- 21187105
TI  - Mechanisms of bi-directional modulation of thalamocortical transmission in barrel
      cortex by presynaptic kainate receptors.
AB  - Presynaptic kainate receptors play an important role in synaptic transmission and
      short-term plasticity to profoundly regulate network activity in many parts of
      the mammalian brain. In primary sensory neocortex, where short-term synaptic
      plasticity is important for receptive field structure and information processing,
      kainate receptors are highly expressed and regulate thalamocortical inputs,
      particularly during development. However, the mechanisms of the kainate receptor
      dependent presynaptic regulation of thalamocortical transmission are unclear. We
      therefore investigated this issue using electrophysiology in neonatal
      thalamocortical slices of barrel cortex combined with pharmacology and
      biochemical analyses. We show that presynaptic kainate receptors can both
      facilitate or depress synaptic transmission depending on the extent of their
      activation. This bi-directional regulation is mediated in part by kainate
      receptors that directly influence thalamocortical axonal excitability, but also
      likely involves receptors acting at thalamocortical terminals to regulate
      transmitter release. The efficacy of kainate in regulating thalamocortical
      transmission is low compared to that reported for other inputs. Consistent with
      this low efficacy, our biochemical analyses indicate that the presynaptic kainate
      receptors regulating neonatal thalamocortical inputs likely lack the high kainate
      affinity GluK4 and 5 subunits. Thus thalamocortical transmission can be bi
      directionally regulated by low affinity kainate receptors through two mechanisms.
      Such presynaptic regulation provides a potentially powerful mechanism to
      influence sensory processing during development of barrel cortex.

PMID- 21187106
TI  - Excitatory synaptic activity is associated with a rapid structural plasticity of
      inhibitory synapses on hippocampal CA1 pyramidal cells.
AB  - Synaptic activity, such as long-term potentiation (LTP), has been shown to induce
      morphological plasticity of excitatory synapses on dendritic spines through the
      spine head and postsynaptic density (PSD) enlargement and reorganization. Much
      less, however, is known about activity-induced morphological modifications of
      inhibitory synapses. Using an in vitro model of rat organotypic hippocampal slice
      cultures and electron microscopy, we studied activity-related morphological
      changes of somatic inhibitory inputs triggered by a brief oxygen-glucose
      deprivation (OGD) episode, a condition associated with a synaptic enhancement
      referred to as anoxic LTP and a structural remodeling of excitatory synapses.
      Three-dimensional reconstruction of inhibitory axo-somatic synapses at different
      times before and after brief OGD revealed important morphological changes. The
      PSD area significantly and markedly increased at synapses with large and complex
      PSDs, but not at synapses with simple, macular PSDs. Activity-related changes of
      PSD size and presynaptic bouton volume developed in a strongly correlated manner.
      Analyses of single and serial sections further showed that the density of
      inhibitory synaptic contacts on the cell soma did not change within 1 h after
      OGD. In contrast, the proportion of the cell surface covered with inhibitory
      PSDs, as well as the complexity of these PSDs significantly increased, with less
      macular PSDs and more complex, segmented shapes. Together, these data reveal a
      rapid activity-related restructuring of somatic inhibitory synapses characterized
      by an enlargement and increased complexity of inhibitory PSDs, providing a new
      mechanism for a quick adjustment of the excitatory-inhibitory balance. This
      article is part of a Special Issue entitled 'Synaptic Plasticity & Interneurons'.

PMID- 21187107
TI  - The temporal dynamics of prospective memory: a review of the ERP and prospective
      memory literature.
AB  - This review article examines the literature using event-related brain potentials
      (ERPs) to study the temporal dynamics of the neurocognitive processes
      underpinning event-based prospective memory (PM). The successful encoding of
      delayed intentions is associated with slow wave activity over the frontal region
      in younger adults and this activity is attenuated in older adults. The
      realization of delayed intentions is associated with distinct components of the
      ERPs that are associated with the detection of a PM cue in the environment
      (N300), the retrieval of an intention from memory (recognition old-new effect),
      signaling the need to switch from the ongoing activity (frontal positivity), and
      configuration of the PM task set (parietal positivity). The development of
      prospective memory across the lifespan appears to reflect development of
      processes associated with retrieval of the cue-intention association from memory,
      and executive processes related to cue detection. The final section of the review
      examines the nature of executive processes that support PM within the context of
      a theory of the supervisory attentional system.

PMID- 21187108
TI  - Voluntary alcohol consumption and plasma beta-endorphin levels in alcohol
      preferring rats chronically treated with levetiracetam: a preliminary study.
AB  - Many recent researches have confirmed the effectiveness of antiepileptic drugs in
      preventing alcohol dependency, whereas our previous study showed that repeated
      treatment with topiramate, a new antiepileptic drug, was effective in increasing
      the plasma levels of beta-endorphin (an endogenous opioid peptide) in rats. It is
      well documented that in humans a genetic deficit of beta-endorphin is often
      associated with alcohol addiction as alcohol consumption elevates the level of
      this peptide. The aim of the present study is multifaceted: to investigate the
      effect of repeated treatment of levetiracetam (50 or 100mg/kg b.w., twice daily)
      on voluntary alcohol intake in alcohol preferring rats (Warsaw High Preferring;
      WHP) and to assess changes in plasma beta-endorphin levels while alcohol is
      available and when it is not available for an extended period of time. We
      observed a noticeable increase in the levels of beta-endorphin in rats with free
      access to alcohol whether in a prolonged levetiracetam-treated or vehicle-treated
      group. However, in the levetiracetam group, a voluntary intake of alcohol
      diminished in comparison with both the pretreatment period and in comparison with
      the vehicle-treated rats. A similar increase in the plasma beta-endorphin levels
      was observed in levetiracetam-treated rats that did not have access to ethanol.
      This finding lets us to believe that levetiracetam may be a promising medication
      in treatment of alcohol dependency as its application leads to the increase in
      the beta-endorphin concentration and ultimately results in reducing deficiency of
      this peptide.

PMID- 21187110
TI  - Turing-Child field underlies spatial periodicity in Drosophila and planarians.
AB  - The regular spatial periodicity manifested in Drosophila gene expression has been
      considered as a test case for the involvement of a Turing system in biology. It
      was expected--if such involvement exists--to find a spatially periodic protein
      distribution where the proteins are Turing morphogens. The failure to find such a
      periodic distribution of Turing proteins, and the experimental findings of the
      involvement of different combinations of regulatory proteins and different
      binding sites for the different stripes of a periodic gene expression, has
      resulted in the dismissal of the involvement of a Turing system in Drosophila
      periodicity and segmentation. But if one is willing to allow a Turing system in
      the level of post-translational modification of proteins instead of in the
      protein level, one can explain the regular spatial periodicity of gene
      expression. The source of the spatial periodicity of gene expression does not lie
      in the regulatory proteins, but in the spatially periodic post-translational
      modification of these broadly distributed upstream regulatory proteins. The post
      translational modification provides the missing spatial information for the
      regular pattern of 14 stripes. We report that such a field with segmental spatial
      periodicity that can affect downstream proteins and modify them post
      translationally and periodically has been observed. This is the Turing-Child (TC)
      field. We explain the recent observation in Drosophila of phosphorylated
      transcription factor distributed with segmental periodicity, the disappearance of
      the spatially periodic gene expression when the regulatory protein loses its
      normal ability to be phosphorylated, and the spatially periodic segmental groove
      formation. Just as the reduction of Turing wavelength causes the appearance of 14
      stripes in Drosophila so it causes the appearance of bipolar 2-headed Planaria.

PMID- 21187109
TI  - A rapid and sensitive fluorometric method for the quantitative analysis of snake
      venom metalloproteases and their inhibitors.
AB  - Metalloproteases are responsible for the hemorrhagic effects of many snake venoms
      and contribute to other pathways that lead to local tissue damage. Methods that
      quantify snake venom metalloproteases (SVMP) are therefore valuable tools in
      research on the clinical, physiological, and biochemical effects of envenomation.
      Comparative analysis of individual, population, and species differences requires
      screening of large numbers of samples and treatments, and therefore require a
      method of quantifying SVMP activity that is simple, rapid, and sensitive. This
      paper demonstrates the properties of a new fluorometric assay of SVMP activity
      that can provide a measure of metalloprotease activity in 1 h. The assay is
      reliable, with variation among replicates sufficiently small to reliably detect
      differences in between species (F(19,60) = 2924, p < 0.001), even for those
      venoms with low overall activity. It is also sensitive enough to detect
      differences among venoms using <2 ng of whole venom protein. We provide an
      example use of this assay to detect the presence of natural SVMP inhibitors in
      minute samples of blood plasma from rock squirrels (S. variegatus), a natural
      prey species for North American rattlesnakes. We propose this assay is a useful
      addition to the set of tools used to characterize venoms, as well as high
      throughput screening of natural or synthetic inhibitors, or other novel
      therapeutic agents against SVMP effects.

PMID- 21187112
TI  - Vibrio cholerae O1 infection in Taiwan.

PMID- 21187113
TI  - The effect of the blood culture bottle type in the rate of direct identification
      from positive cultures by matrix-assisted laser desorption/ionisation time-of
      flight (MALDI-TOF) mass spectrometry.

PMID- 21187111
TI  - Differential expression of genes in the earthworm Eisenia fetida following
      exposure to Escherichia coli O157:H7.
AB  - In this study, suppression subtractive hybridization was used to construct
      forward and reverse cDNA libraries to identify genes involved in the response of
      Eisenia fetida after exposure to Escherichia coli O157:H7. We cloned 1428 cDNAs
      or expressed sequence tags (ESTs), of which 738 were confirmed to be
      differentially expressed on dot blotting analysis. A total of 394 good-quality
      ESTs (GenBank dbEST accession numbers HO001170-HO001563) were obtained from the
      raw clone sequences after cleaning. The genes were associated with metabolism
      (10%), transport (10%), translation (5%), immunity (2%), and the cytoskeleton
      (1%). Thirteen candidates were selected to assess expression levels in earthworms
      exposed to artificially contaminated soil by real-time PCR. The translated amino
      acid sequences of clones were similar to fibrinolytic protease 1, extracellular
      globin-3, myosin essential light chain, lumbrokinase, lysozyme, ferritin, ATP
      synthase F0 subunit 6, and hsp 70. Characterization of differential gene
      expression in the earthworm E. fetida on exposure to E. coli O157:H7 expands our
      understanding of the molecular mechanisms of interactions at the earthworm
      pathogen interface.

PMID- 21187114
TI  - Design of an in-dwelling cannula for convection-enhanced delivery.
AB  - Failures of recent convection-enhanced delivery (CED) trials have underscored the
      need for improved CED cannulae. This study presents a novel in-dwelling cannula
      targeted for use in upcoming neuro-oncological or neurodegeneration trials. The
      cannula is reflux-resistant and easily integrated into clinical workflows. The
      cannula was evaluated in non-human primate CED studies performed with magnetic
      resonance imaging (MRI) to validate the effectiveness and safety of the infusion.

PMID- 21187115
TI  - Design, fabrication and evaluation of a conforming circumpolar peripheral nerve
      cuff electrode for acute experimental use.
AB  - Nerve cuff electrodes are a principle tool of basic and applied electro
      neurophysiology studies and are championed for their ability to achieve good
      nerve recruitment with low thresholds. We describe the design and method of
      fabrication for a novel circumpolar peripheral nerve electrode for acute
      experimental use. This cylindrical cuff-style electrode provides approximately
      270 degrees  of radial electrode contact with a nerve for each of an arbitrary
      number of contacts, has a profile that allows for simple placement and removal in
      an acute nerve preparation, and is designed for adjustment of the cylindrical
      diameter to ensure a close fit on the nerve. For each electrode, the electrical
      contacts were cut from 25 MUm platinum foil as an array so as to maintain their
      positions relative to each other within the cuff. Lead wires were welded to each
      intended contact. The structure was then molded in silicone elastomer, after
      which the individual contacts were electrically isolated. The final electrode was
      curved into a cylindrical shape with an inner diameter corresponding to that of
      the intended target nerve. The positions of these contacts were well maintained
      during the molding and shaping process and failure rates during fabrication due
      to contact displacements were very low. Established electrochemical measurements
      were made on one electrode to confirm expected behavior for a platinum electrode
      and to measure the electrode impedance to applied voltages at different
      frequencies. These electrodes have been successfully used for nerve stimulation,
      recording, and conduction block in a number of different acute animal experiments
      by several investigators.

PMID- 21187116
TI  - Multichannel matching pursuit validation and clustering--a simulation and
      empirical study.
AB  - INTRODUCTION: Multichannel matching pursuit (MMP) is a relatively new method that
      can be applied to electroencephalogram (EEG) signals in combination with inverse
      modelling. However, limitations of MMP have not been adequately tested. The aims
      of this study were to investigate how the accuracy of MMP algorithm is altered
      due to increased number of brain sources and increased noise level, and to
      implement and test a modified K-means clustering algorithm in order to group
      similar MMP atoms in time-frequency and space between subjects together. METHODS:
      Four groups of 20 EEG signals were simulated. The groups consisted of simulations
      with 5, 10, 15, and 20 brain sources. The accuracy of MMP algorithm was first
      tested on increasing number of sources. Then, different levels of noise were
      added to the simulations and accuracy of the algorithm was tested on increasing
      noise level. K-means clustering algorithm was tested on 4 datasets (5, 10, 15,
      and 20 sources) of 10 similar phantom subjects. Finally, the clustering algorithm
      was tested on empirical somatosensory evoked potential and brainstem evoked
      potential data. RESULTS: The MMP accuracy decreased as the number of sources
      increased and MMP accuracy was robust to noise. Furthermore, we found that when
      applying the clustering method to a subject group's MMP data, the clustering
      method grouped the similar atoms between subjects correctly. CONCLUSION: The MMP
      and clustering method proved to be an efficient way to group similar brain
      activity and thus study differences in brain activation sequence to sensory
      stimulation between groups of subjects.

PMID- 21187117
TI  - Detection of chimpanzee polyomavirus-specific antibodies in captive and wild
      caught chimpanzees using yeast-expressed virus-like particles.
AB  - Chimpanzee polyomavirus (ChPyV) was originally detected in the faeces of a
      captive chimpanzee by random screening using broad-spectrum PCR. Its
      pathogenicity and the distribution among chimpanzees are unknown so far. Here,
      the major capsid protein VP1 of ChPyV was expressed in yeast cells. Virus-like
      particles (VLPs) with a diameter of approximately 45nm were demonstrated although
      the efficiency of VLP formation was low as compared to monkey polyomavirus SV40
      VLPs. The ChPyV-VLP preparation did not agglutinate human erythrocytes. Low cross
      reactions between ChPyV- and SV40-VLP-specific sera were detected by
      immunoblotting, but not by ELISA. Testing of 163 sera derived from captive and
      wild-caught healthy chimpanzees using an ELISA based on the ChPyV-VLPs resulted
      in 11.7% positive results, ranging from 0% to 56% in different groups. The VLPs
      may be used in future to assess the distribution of ChPyV infections among other
      animal species and humans.

PMID- 21187118
TI  - Construction of cell penetrating peptide vectors with N-terminal stearylated
      nuclear localization signal for targeted delivery of DNA into the cell nuclei.
AB  - Cellular uptake and nuclear localization are two barriers to gene delivery. Here,
      we designed new gene delivery carriers with an N-terminal stearylated (STR)
      nuclear localization signal (NLS), PKKKRKV, present in the Simian Virus 40 large
      T antigen with the aim to overcome limitations, such as cell membrane and nuclear
      pores, offering attractive possibilities to enhance gene delivery. Four vectors
      with different structures of N-stearylated nuclear localization signal
      octaarginine peptide (STR-PKKKRKV-R(8) or STR-NLS-R(8), STR-VKRKKKP-R(8) or STR
      reverse NLS-R(8), PKKKRKV-R(8) or NLS-R(8), and VKRKKKP-R(8) or reverse NLS-R(8))
      were compared. The gene expression mediated by these vectors in dividing and non
      dividing cells (both in 293T and HeLa cell lines) was investigated. The most
      efficient N/P ratio was 4 for STR-PKKKRKV-R(8,) STR-VKRKKKP-R(8,) and 0.25 for
      PKKKRKV-R(8), VKRKKKP-R(8.) The maximum transfection activity of these vehicles
      (VKRKKKP-R(8)) was up to 80% as effective as jetPEITM and the vehicles did not
      exhibit cytotoxicity. Interestingly, N-stearylated peptides presented lower
      transfection activity compared to peptides without N-stearylation at lower N/P
      ratios (0.25 to 1). Confocal study showed that the vectors could effectively
      promote the nuclear translocation.

PMID- 21187119
TI  - Unpredictable chronic stress model in zebrafish (Danio rerio): behavioral and
      physiological responses.
AB  - Zebrafish (Danio rerio) have emerged as a promising model organism to study
      development, toxicology, pharmacology, and neuroscience, among other areas.
      Despite the increasing number of studies using zebrafish, behavioral studies with
      this species are still elementary when compared to rodents. The aim of this study
      was to develop a model of unpredictable chronic stress (UCS) in zebrafish. We
      evaluated the effects of UCS protocol during 7 or 14 days on behavioral and
      physiological parameters. The effects of stress were evaluated in relation to
      anxiety and exploratory behavior, memory, expression of corticotrophin-releasing
      factor (CRF) and glucocorticoid receptor (GR), and cortisol levels. As expected,
      UCS protocol increased the anxiety levels, impaired cognitive function, and
      increased CRF while decreased GR expression. Moreover, zebrafish submitted to 7
      or 14 days of UCS protocol presented increased cortisol levels. The protocol
      developed here is a complementary model for studying the neurobiology and the
      effects of chronic stress in behavioral and physiological parameters. In
      addition, this protocol is less time consuming than standard rodent models
      commonly used to study chronic stress. These results confirm UCS in zebrafish as
      an adequate model to preclinical studies of stress, although further studies are
      warranted to determine its predictive validity.

PMID- 21187120
TI  - Electrophysiology of appetitive taste and appetitive taste conditioning in
      humans.
AB  - The present study examines two novel aspects of appetitive processing and
      conditioning: the electrophysiological response to (a) the appetitive taste of a
      sweet fluid and (b) appetitively/taste conditioned visual stimuli. Event-related
      potentials (ERPs) were recorded from 32 subjects while they performed a taste
      conditioning task, in which two symbols were paired with a sweet or a neutral
      fluid. The results show a clear P1/N1/P2 complex, and a late positive potential
      (P3) with maxima at right fronto-central electrode sites, in response to the
      taste stimuli. Of these components particularly the P3 showed robust differences
      between the sweet and neutral taste. In addition, the electrophysiological
      response to the taste conditioned stimuli (CS), also showed the expected
      differences for both P2 and P3 at frontocentral electrodes. The present data
      demonstrate that the employed paradigm is a useful methodology to study the
      electrophysiological responses to unconditioned appetitive stimuli. Since
      appetitive conditioning is assumed to be disturbed in many psychopathological
      conditions, such as substance dependence, depression and eating disorders, this
      paradigm could be employed to get more insight in these conditions in humans.

PMID- 21187121
TI  - Molecular cloning of anti-Mullerian hormone from the American alligator,
      Alligator mississippiensis.
AB  - Anti-Mullerian hormone (AMH) plays an important role in male sex differentiation
      in vertebrates. AMH produced by Sertoli cells of the fetal testis induces
      regression of the Mullerian duct in mammalian species. In alligators, sexual
      differentiation is controlled by the temperature during egg incubation, termed
      temperature-dependent sex determination (TSD). The TSD mechanism inducing sex
      differentiation is thought to be unique and different from that of genetic sex
      determination as no gene such as the SRY of mammals has been identified. However,
      many of the genes associated with gonadal differentiation in mammals also are
      expressed in the developing gonads of species exhibiting TSD. To clarify the
      molecular mechanisms associated with gonad formation during the temperature
      sensitive period (TSP), we have cloned the full length AMH gene in the alligator,
      and quantitatively compared mRNA expression patterns in the gonad-adrenal
      mesonephros (GAM) complex isolated from alligator embryos incubated at male and
      female producing temperatures. The deduced amino acid sequence of the alligator
      AMH cDNA showed high identity (59-53%) to avian AMH genes. AMH mRNA expression
      was high in the GAM of male alligator embryos at stage 24 (immediately after sex
      determination) and hatchlings, but suppressed in the GAM of estrogen-exposed
      hatchlings incubated at the male-producing temperature. In the alligator AMH
      proximal promoter, a number of transcriptional factors (for SF-1. GATA, WT-1 and
      SOX9) binding elements were also identified and they exhibit a conserved pattern
      seen in other species. SOX9 up-regulates transcriptional activity through the
      amAMH promoter region. These results suggested that AMH and SOX9 play important
      roles in TSD of the American alligator.

PMID- 21187122
TI  - Aryl hydrocarbon receptor activation in lactotropes and gonadotropes interferes
      with estradiol-dependent and -independent preprolactin, glycoprotein alpha and
      luteinizing hormone beta gene expression.
AB  - Arylhydrocarbon receptor (Ahr) activation by 2,3,7,8-tetrachlordibenzo-p-dioxin
      (TCDD) interferes with female reproductive functions, but there is little
      information on the specific targets of TCDD in the hypothalamic-pituitary-gonadal
      (HPG) axis. In these studies, we found that TCDD upregulated known AhR target
      genes, cytochrome p450 1a1 (Cyp1a1), Cyp1a2 and Cyp1b1 in the rat pituitary
      gland. Moreover, 75% of pituitary lactotropes and 45% of gonadotropes contained
      Ahr mRNA, and most Ahr-containing cells were estrogen receptor 1 (Esr1)-positive.
      TCDD abrogated estradiol (E(2))-induced prolactin (Prl) expression in vivo and in
      vitro; conversely, E(2) blocked TCDD upregulation of luteinizing hormone beta
      (Lhb) and glycoprotein hormone alpha polypeptide (Cga) expression. TCDD had no
      effect on levels of Ahr mRNA, but upregulated Esr1 mRNA. E(2) independently
      repressed Ahr and Esr1 expression and blocked TCDD upregulation of Esr1. Thus,
      complex interactions between Ahr and Esr alter Prl and luteinizing hormone (LH)
      synthesis by direct actions in lactotropes and gonadotropes. These findings
      provide important insights into how TCDD disrupts female reproductive functions.

PMID- 21187123
TI  - Targeted expression of islet neogenesis associated protein to beta cells enhances
      glucose tolerance and confers resistance to streptozotocin-induced hyperglycemia.
AB  - Islet neogenesis associated protein (INGAP) stimulates experimental pancreatic
      islet growth, as evidenced by elevated markers of beta cell mass, in rodents,
      dogs and primates. Previous analyses of mice that have a transgenic expression of
      INGAP targeted to the exocrine pancreas have indicated additional biological
      activity attributed to INGAP. In this study we report on mice with a targeted
      expression of INGAP to the islet beta cell. The beta cell transgenic mice (IP
      INGAP) showed enhanced normalization of blood glucose during IPGTT. Further, IP
      INGAP mice had a significant delay in development of hyperglycemia following a
      diabetogenic dose of streptozotocin. INGAP conferred beta cell protection and
      enhanced islet function. Analysis of oxidative stress genes in IP-INGAP mice
      revealed a decrease in islet expression of the NADPH oxidase, NOX1, in both basal
      state and in response to pro-inflammatory cytokine stimulation. These data are
      consistent with a pleiotropic role for INGAP and reveal new pathways to target in
      the discovery of improved diabetic therapies.

PMID- 21187124
TI  - ATP differentially upregulates fibroblast growth factor 2 and transforming growth
      factor alpha in neonatal and adult mice: effect on neuroproliferation.
AB  - Multiple neurotrophic factors play a role in proliferation, differentiation and
      survival in the olfactory epithelium (OE); however, the signaling cascade has not
      been fully elucidated. We tested the hypotheses that ATP induces the synthesis
      and secretion of two neurotrophic factors, fibroblast growth factor 2 (FGF2) and
      transforming growth factor alpha (TGFalpha), and that these neurotrophic factors
      have a role in inducing proliferation. Protein levels of FGF2 and TGFalpha were
      increased 20 h post-intranasal instillation of ATP compared to vehicle control in
      adult Swiss Webster mice. Pre-intranasal treatment with purinergic receptor
      antagonist pyridoxal-phosphate-6-azophenyl-20,40-disulfonic acid (PPADS)
      significantly blocked this ATP-induced increase, indicating that upregulation of
      FGF2 and TGFalpha expression is mediated by purinergic receptor activation.
      However, in neonatal mouse, intranasal instillation of ATP significantly
      increased the protein levels of FGF2, but not TGFalpha. Likewise, ATP evoked the
      secretion of FGF2, but not TGFalpha, from neonatal mouse olfactory epithelial
      slices and PPADS significantly blocked ATP-evoked FGF2 release. To determine the
      role of FGF2 and TGFalpha in inducing proliferation, 5-bromo-2-deoxyuridine
      (BrdU) incorporation was examined in adult olfactory epithelium. Intranasal
      treatment with FGF receptor inhibitor PD173074 or epidermal growth factor
      receptor inhibitor AG1478 following ATP instillation significantly blocked ATP
      induced BrdU incorporation. Collectively, these data demonstrate that ATP induces
      proliferation in adult mouse olfactory epithelium by promoting FGF2 and TGFalpha
      synthesis and activation of their receptors. These data suggest that different
      mechanisms regulate neurogenesis in neonatal and adult OE, and FGF2 and TGFalpha
      may have different roles throughout development.

PMID- 21187125
TI  - Maternal high-fat intake alters presynaptic regulation of dopamine in the nucleus
      accumbens and increases motivation for fat rewards in the offspring.
AB  - High caloric intake during early postnatal development can have long term
      consequences for the offspring. We previously reported that the adult offspring
      of dams fed a high-fat diet during the last week of gestation and throughout
      lactation display blunted locomotor response to amphetamine (AMP) and reduced
      sensitization to the drug compared to offspring of control diet dams. Here, we
      report that the subsensitivity of high-fat offspring to AMP's locomotor stimulant
      action reflects, at least in part, altered regulation of nucleus accumbens (NAc)
      dopamine (DA) transmission. When compared to controls, the DA response of high
      fat animals to AMP, as measured with microdialysis, was attenuated in the NAc,
      but unaffected in the prefrontal cortex (PFC). A relatively higher activity of
      NAc synaptosomal DA transporter sites without changes in vesicular monoamine
      transporter (VMAT) uptake capacity was also observed in high-fat offspring.
      Moreover, ventral tegmental area (VTA) D(2) receptor mRNA levels were decreased
      in high-fat offspring, suggesting a reduction in DA release-regulating D(2)
      autoreceptors in terminal regions such as the NAc. The magnitude of locomotor
      response to D(2/3) receptor activation (with quinpirole) was greater in high-fat
      than in control animals despite having comparable postsynaptic D(2) mRNA levels
      in the NAc. Finally, while operant responding for a sugar-enriched food reward
      did not differ between diet groups, high-fat offspring displayed increased
      operant responding for a fat-enriched reward compared to controls. These findings
      add to mounting evidence that early life exposure to elevated dietary maternal
      fat can lead to long lasting changes in DA-mediated behavioral responses to
      stimulant drugs and fat-enriched foods.

PMID- 21187127
TI  - Formulation and pharmacokinetic evaluation of hard gelatin capsule encapsulating
      lyophilized Vasa Swaras for improved stability and oral bioavailability of
      vasicine.
AB  - The oral bioavailability of vasicine (1) was investigated in hard gelatin
      capsules of lyophilized Vasa Swaras (aqueous extract of Adhatoda vasica
      Nees.,Fam.: Acanthaceae) The rat pharmacokinetic profile of lyophilized Vasa
      Swaras, Vasa Swaras, vasicine (1) (chief marker compounds of A. vasica) and a
      marketed capsule formulation of A. vasica were compared. Vasicine (1) was found
      to be more orally bioavailable from lyophilized Vasa Swaras, with an overall
      minor conversion to vasicinone (2).

PMID- 21187128
TI  - Negative anticipatory contrast: does it involve anticipation of an impending
      reward?
AB  - Negative anticipatory contrast (NAC) corresponds to the suppression in
      consumption of a first rewarding substance (e.g., saccharin 0.15%) when it is
      followed daily by a second preferred substance (e.g., sucrose 32%). The NAC has
      been interpreted as resulting from anticipation of the impending preferred reward
      and its comparison with the currently available first reward [Flaherty, C.F.,
      Rowan, G.A., 1985. Anticipatory contrast: within-subjects analysis. Anim. Learn.
      Behav. 13, 2-5]. In this context, one should expect that devaluation of the
      preferred substance after the establishment of the NAC would either reduce or
      abolish the contrast effect. However, contrary to this prediction, the results of
      the present study show that the NAC is insensitive to devaluation of the second,
      preferred, substance. This allows one to question that interpretation. The
      results reported in this study support the view that the NAC effect is controlled
      by memory of the relative value of the first solution, which is updated daily by
      means of both a gustatory and/or post-ingestive comparison of the first and
      second solutions, and memory of past pairings.

PMID- 21187129
TI  - Attack or retreat: contrasted defensive tactics used by Cyprian honeybee colonies
      under attack from hornets.
AB  - This study describes the tactics used by Cyprian honeybees (Apis mellifera
      cypria) to defend their colonies against hornet (Vespa orientalis orientalis)
      attacks. We use simulated hornet attacks and a combination of video recordings
      and image analysis to reveal, for the first time, contrasted intra-subspecies
      defensive tactics that operate at the colony level during predation. In some
      colonies, when attacked, the numbers of guards at the hive entrance increases
      rapidly to attack, engulf, and kill invading hornets. In other colonies, guards
      avoid conflicts with hornets by retreating gradually and by forming a defensive
      line of honeybees at the hive entrance. Retreater colonies have propolis walls at
      the hive entrances with small apertures that are too narrow to allow the hornet
      to access the hive and that therefore reinforces entrance protection. On the
      contrary, attacker colonies have propolis walls with large openings through which
      the hornet can pass; these bees block the hornet's access by intensively guarding
      the hive entrance. We experimentally destroy propolis walls to test whether
      colonies consistently rebuild walls with the same intrinsic characteristics and
      we also monitor the survival rate of each anti-predator tactic after massive
      natural predation by hornets.

PMID- 21187130
TI  - Little and often? Maintaining continued performance in an automated T-maze for
      mice.
AB  - Operant and maze tasks in mice are limited by the small number of trials possible
      in a session before mice lose motivation. We hypothesized that by manipulating
      reward size and session length, motivation, and hence performance, would be
      maintained in an automated T-maze. We predicted that larger rewards and shorter
      sessions would improve acquisition; and smaller rewards and shorter sessions
      would maintain higher and less variable performance. Eighteen C57BL/6J mice (9
      per sex) acquired (criterion 8/10 correct) and performed a spatial
      discrimination, with one of 3 reward sizes (.02, .04, or .08 g) and one of 3
      session schedules (15, 30, or 45 min sessions). Each mouse had a total of 360 min
      of access to the maze per night, for two nights, and averaged 190 trials.
      Analysis used split-plot GLM with contrasts testing for linear effects.
      Acquisition of the discrimination was unaffected by reward size or session
      length/interval. After-criterion average performance improved as reward size
      decreased. After-criterion variability in performance was also affected.
      Variability increased as reward size increased. Session length/interval did not
      affect any outcome. We conclude that an automated maze, with suitable reward
      sizes, can sustain performance with low variability, at 5-10 times faster than
      traditional methods.

PMID- 21187126
TI  - Neurodegeneration in glaucoma: progression and calcium-dependent intracellular
      mechanisms.
AB  - Glaucoma is an age-related optic neuropathy involving sensitivity to ocular
      pressure. The disease is now seen increasingly as one of the central nervous
      system, as powerful new approaches highlight an increasing number of similarities
      with other age-related neurodegenerations such as Alzheimer's and Parkinson's.
      While the etiologies of these diseases are diverse, they involve many important
      common elements including compartmentalized programs of degeneration targeting
      axons, dendrites and finally cell bodies. Most age-related degenerations display
      early functional deficits that precede actual loss of neuronal substrate. These
      are linked to several specific neurochemical cascades that can be linked back to
      dysregulation of Ca(2+)-dependent processes. We are now in the midst of
      identifying similar cascades in glaucoma. Here we review recent evidence on the
      pathological progression of neurodegeneration in glaucoma and some of the Ca(2+)
      dependent mechanisms that could underlie these changes. These mechanisms present
      clear implications for efforts to develop interventions targeting neuronal loss
      directly and make glaucoma an attractive model for both interrogating and
      informing other neurodegenerative diseases.

PMID- 21187131
TI  - Domestication effects on behavioural synchronization and individual distances in
      chickens (Gallus gallus).
AB  - Behavioural synchrony (allelomimetic behaviour), and inter-individual distances
      are aspects of social and anti-predator strategies which may have been affected
      by domestication. Chickens are known to adjust synchronization and inter
      individual distances depending on behaviour. We hypothesized that White Leghorn
      (WL) chickens would show less synchronized behaviour than the ancestor, the red
      jungle fowl (RJF). Sixty birds, 15 female and 15 male WL and the same number of
      RJF (28 weeks old) were studied in groups of three in furnished pens (1 m*2 m)
      for 24 consecutive hours per group, following 24 h of habituation. Video tapes
      covering 4 h per group (dawn, 9-10 am, 1-2 pm and dusk) were analysed. Red
      junglefowl perched significantly more, but there were no breed effects on the
      frequency or daily rhythm of any other activities, or on average inter-individual
      distances. Red junglefowl were more synchronized during perching and a tendency
      for the same was found for social behaviour. After performance of the two most
      synchronized behaviours, perching and comfort behaviour, individual distance
      increased more for RJF than WL. According to this study domestication of chickens
      appears not to have significantly altered the relative frequencies of different
      activities or average inter-individual distances, but have caused some changes in
      behavioural synchronization and maintenance of activity-specific inter-individual
      distances in chickens. The changes may indicate an adaptive response to captivity
      and domestication.

PMID- 21187132
TI  - Drugs for youth via Internet and the example of mephedrone.
AB  - Recently a new class of "designer drugs" has emerged on the drugs abuse market,
      known as "legal highs". Such drugs are legal to use and possess, and legal to
      supply. Mephedrone, a central nervous system stimulant, is the most widely
      experienced "legal high". This review presents any available information about
      psychoactive properties, safety profile, clinical data, and legislation of the
      new "legal high" and emphasizes the role of Internet with mephedrone's expansion.
      Available data were collected by various literature search engines and World Wide
      Web. All valuable information about psychoactive properties, safety profile and
      clinical data for mephedrone and its use as "legal high" were managed to spot and
      summarise. Internet plays a significant role for the distribution of "legal
      highs", becoming one of the major "drug market". Adolescents and young adults who
      are curious about drugs may search on the Internet and thereby become exposed to
      thousands of sites that expound upon the positive effects of drugs and downplay
      or deny any negative effects. Use of mephedrone is mainly a youth phenomenon. The
      hazardous side-effects are strong desire to re-dose, uncomfortable changes in
      body temperature and heart rate, hallucinations and psychosis.

PMID- 21187133
TI  - Systems biology approach to study permeability of paracetamol and its solid
      dispersion.
AB  - Physiological changes that take place at cellular level are usually reflective of
      their level of gene expression. Different formulation excipients have an impact
      on physiological behavior of the exposed cells and in turn affect transporter
      genes, enterocyte-mediated metabolism and toxicity biomarkers. The aim of this
      study was to prepare solid dispersion of paracetamol and evaluate genetic changes
      that occur in Caco-2 cell lines during the permeability of paracetamol alone and
      paracetamol solid dispersion formulations. Paracetamol-PEG 8000 solid dispersion
      was prepared by melt fusion method and the formulation was characterised using
      differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and
      Fourier transform infrared spectroscopy (FTIR). Formulation of solid dispersion
      resulted in the conversion of crystalline drug into an amorphous form.
      Permeability studies showed that paracetamol absorption was higher from the solid
      dispersion formulation. DNA microarrays analysis was carried out in order to
      investigate the involvement of any efflux/uptake transporters in paracetamol or
      its solid dispersion permeability. Neither transporter carriers nor efflux
      proteins were found to be involved in the absorption of paracetamol or its PEG
      solid dispersion. Gene expression analysis established that paracetamol toxicity
      was potentially reduced upon formulation into solid dispersion when ATP binding
      cassette (ABC) and solute carrier transporter (SLC) genes were analyzed.

PMID- 21187134
TI  - The butterfly effect: a physical phenomenon of hypromellose matrices during
      dissolution and the factors affecting its occurrence.
AB  - A phenomenon was observed for the behavior of hypromellose matrices during
      dissolution. The tablet laminated radially, with both edges curled outwards,
      forming a "butterfly" shape. The butterfly effect is thus coined to describe this
      behavior. Due to the flamboyant shape assumed by the hydrated matrix, the
      apparent surface area for drug release was significantly increased. This study
      attempted to elucidate mechanistically the cause of this butterfly effect. Two
      formative mechanisms were proposed based on the behavior of moving solvent fronts
      and the anisotropic expansion of materials in solution. It was hypothesized that
      the particle size of hypromellose, applied compaction force used and proportions
      of both insoluble and soluble excipients contributed to the butterfly effect. The
      influence of the expanded shape on the mechanism and rate of drug release was
      also investigated. Matrix formulation was an important factor. Greater drug
      release was observed when the butterfly-shaped hydrated matrix was formed. The
      drug release profiles generally fitted the Higuchi and Korsmeyer-Peppas
      equations, indicating a combination of both diffusion and erosional drug release
      mechanisms. A combination of both fine and coarse hypromellose size fractions and
      adequate compaction force (more than 3 kN) were necessary for the manifestation
      of the butterfly effect.

PMID- 21187135
TI  - Context-dependent modulation of auditory processing by serotonin.
AB  - Context-dependent plasticity in auditory processing is achieved in part by
      physiological mechanisms that link behavioral state to neural responses to sound.
      The neuromodulator serotonin has many characteristics suitable for such a role.
      Serotonergic neurons are extrinsic to the auditory system but send projections to
      most auditory regions. These projections release serotonin during particular
      behavioral contexts. Heightened levels of behavioral arousal and specific
      extrinsic events, including stressful or social events, increase serotonin
      availability in the auditory system. Although the release of serotonin is likely
      to be relatively diffuse, highly specific effects of serotonin on auditory neural
      circuitry are achieved through the localization of serotonergic projections, and
      through a large array of receptor types that are expressed by specific subsets of
      auditory neurons. Through this array, serotonin enacts plasticity in auditory
      processing in multiple ways. Serotonin changes the responses of auditory neurons
      to input through the alteration of intrinsic and synaptic properties, and alters
      both short- and long-term forms of plasticity. The infrastructure of the
      serotonergic system itself is also plastic, responding to age and cochlear
      trauma. These diverse findings support a view of serotonin as a widespread
      mechanism for behaviorally relevant plasticity in the regulation of auditory
      processing. This view also accommodates models of how the same regulatory
      mechanism can have pathological consequences for auditory processing.

PMID- 21187138
TI  - Combining rigour with relevance: a novel methodology for testing Chinese herbal
      medicine.
AB  - BACKGROUND: There is a need to develop an evidence base for Chinese herbal
      medicine (CHM) that is both rigorous and reflective of good practice. This paper
      proposes a novel methodology to test individualised herbal decoctions using a
      randomised, double blinded, placebo controlled clinical trial. METHOD: A
      feasibility study was conducted to explore the role of CHM in the treatment of
      endometriosis. Herbal formulae were pre-cooked and dispensed as individual doses
      in sealed plastic sachets. This permitted the development and testing of a
      plausible placebo decoction. Participants were randomised at a distant pharmacy
      to receive either an individualised herbal prescription or a placebo. RESULTS:
      The trial met the predetermined criteria for good practice. Neither the
      participants nor the practitioner-researcher could reliably identify group
      allocation. Of the 28 women who completed the trial, in the placebo group (n=15)
      3 women (20%) correctly guessed they were on placebo, 8 (53%) thought they were
      on herbs and 4 (27%) did not know which group they had been allocated to. In the
      active group (n=13) 2 (15%) though they were on placebo, 8 (62%) thought they
      were on herbs and 3 (23%) did not know. Randomisation, double blinding and
      allocation concealment were successful and the study model appeared to be
      feasible and effective. CONCLUSION: It is now possible to subject CHM to rigorous
      scientific scrutiny without compromising model validity. Improvement in the
      design of the placebo using food colourings and flavourings instead of dried food
      will help guarantee the therapeutic inertia of the placebo decoction.

PMID- 21187136
TI  - Modulation of hair cell efferents.
AB  - Outer hair cells (OHCs) amplify the sound-evoked motion of the basilar membrane
      to enhance acoustic sensitivity and frequency selectivity. Medial olivocochlear
      (MOC) efferents inhibit OHCs to reduce the sound-evoked response of cochlear
      afferent neurons. OHC inhibition occurs through the activation of postsynaptic
      alpha9alpha10 nicotinic receptors tightly coupled to calcium-dependent SK2
      channels that hyperpolarize the hair cell. MOC neurons are cholinergic but a
      number of other neurotransmitters and neuromodulators have been proposed to
      participate in efferent transmission, with emerging evidence for both pre- and
      postsynaptic effects. Cochlear inhibition in vivo is maximized by repetitive
      activation of the efferents, reflecting facilitation and summation of transmitter
      release onto outer hair cells. This review summarizes recent studies on cellular
      and molecular mechanisms of cholinergic inhibition and the regulation of those
      molecular components, in particular the involvement of intracellular calcium.
      Facilitation at the efferent synapse is compared in a variety of animals, as well
      as other possible mechanisms of modulation of ACh release. These results suggest
      that short-term plasticity contributes to effective cholinergic inhibition of
      hair cells.

PMID- 21187139
TI  - The plate half-full: status of research on the mechanisms of dietary restriction
      in Drosophila melanogaster.
AB  - It has been almost two decades since dietary restriction was first shown to
      increase Drosophila lifespan. Since then, understanding this phenomenon advanced
      as groups worked to identify what quality of restricted diet matters: calories or
      a specific nutrient. The problem is complex because is it difficult to measure
      what a fly actually consumes. A powerful solution uses the geometric framework of
      nutrition where diets in many combinations can be tested for their effects on
      lifespan and reproduction while measuring intake. Applied to Drosophila, it is
      now clear that specific nutrients, not calories, mediate longevity. The geometric
      framework also reveals a nutritional basis for the trade-off between reproduction
      and lifespan. This complements a stable-isotope analysis that tracked the
      allocation of nitrogen, carbon and essential amino acids into eggs versus
      reproduction. Together, these studies show that it is not possible to explain how
      DR extends lifespan through a mechanism were resources are simply reallocated to
      somatic maintenance away from reproduction. Although promising in principle,
      genetic analysis of DR mechanisms has had limited success. To be productive,
      studies must include enough diets at appropriate concentrations. In reviewing the
      best data, there is little evidence to date for any gene to be required for DR to
      increase Drosophila lifespan, including insulin signaling or 4eBP. Strong
      analyses of genes required for DR should be a priority in future research with
      Drosophila and this may be made most robust by considering the effect of mutants
      in the context of the geometric framework.

PMID- 21187137
TI  - Noise-induced changes in gene expression in the cochleae of mice differing in
      their susceptibility to noise damage.
AB  - The molecular mechanisms underlying the vast differences between individuals in
      their susceptibility to noise-induced hearing loss (NIHL) are unknown. The
      present study demonstrated that the effects of noise over-exposure on the
      expression of molecules likely to be important in the development of NIHL differ
      among inbred mouse strains having distinct susceptibilities to NIHL including B6
      (B6.CAST) and 129 (129X1/SvJ and 129S1/SvImJ) mice. The noise-exposure protocol
      produced a loss of 40 dB in hearing sensitivity in susceptible B6 mice, but no
      loss for the two resistant 129 substrains. Analysis of gene expression in the
      membranous labyrinth 6 h following noise exposure revealed upregulation of
      transcription factors in both the susceptible and resistant strains. However, a
      significant induction of genes involved in cell-survival pathways such as the
      heat shock proteins HSP70 and HSP40, growth arrest and DNA-damage-inducible
      protein 45beta (GADD45beta), and CDK-interacting protein 1 (p21(Cip1)) was
      detected only in the resistant mice. Moreover, in 129 mice significant
      upregulation of HSP70, GADD45beta, and p21(Cip1) was confirmed at the protein
      level. Since the functions of these proteins include roles in potent anti
      apoptotic cellular pathways, their upregulation may contribute to protection from
      NIHL in the resistant 129 mice.

PMID- 21187140
TI  - Stress hormones increase cell proliferation and regulates interleukin-6 secretion
      in human oral squamous cell carcinoma cells.
AB  - Patients with oral cancer can have high psychological distress levels, but the
      effects of stress-related hormones on oral cancer cells and possible mechanisms
      underlying these relationships are unknown. In this study, we have investigated
      the effects of stress-related hormones on interleukin-6 (IL-6) secretion and
      proliferation of oral squamous cell carcinoma (OSCC) cells. The effects of
      norepinephrine (NE), and cortisol were studied in SCC9, SCC15, and SCC25 cells
      and effects of isoproterenol in SCC9 and SCC25 cells. Real-time PCR studies
      revealed constitutive beta1- and beta2-adrenergic receptors (beta-ARs) expression
      in the SCC9, SCC15, and SCC25 cells. The results showed that NE and isoproterenol
      significantly enhanced IL-6 mRNA expression and protein production in
      supernatants of SCC9 and SCC25 cells. Physiological stress levels of NE and
      isoproterenol (10 MUM) at 1 h elicited the most robust IL-6 increase. Regarding
      IL-6 secretion, 10 MUM NE induced a 5-fold increase at 1 h, 3.7-fold increase at
      6 h, and 3.2-fold at 24 h in SCC9 cells. These effects were blocked by the beta
      adrenergic antagonist propranolol, supporting a role for beta-ARs in IL-6
      secretion. The effects of cortisol varied according to the hormone concentration.
      Pharmacological concentrations of cortisol (1000 nM) inhibited IL-6 production by
      SCC9 and SCC25 cells. Cortisol dose that simulates stress conditions (10 nM)
      tended to increase IL-6 expression in SCC9 cells. Hormonal doses that simulate
      stress conditions (10 MUM NE, at 6 h in SCC9 and SCC15 cells and 10 nM cortisol,
      at 48 h in SCC15 cells) stimulated increased cell proliferation. Treatment of
      SCC9 cells with IL-6 neutralizing ab (10 MUg/mL) partially inhibited NE-induced
      proliferation. Finally, 20 OSCC biopsies were shown to express beta1- and beta2
      ARs. These findings suggest that stress hormones can affect oral cancer cells
      behavior.

PMID- 21187141
TI  - A conceptual revolution in the relationships between the brain and immunity.

PMID- 21187142
TI  - Metal ion stimulators of PDE5 cause similar conformational changes in the enzyme
      as does cGMP or sildenafil.
AB  - Purified PDE5 preparations exhibited variable proportions of two mobility forms
      (Bands 2 and 3) by native PAGE. Treatment of recombinant or native PDE5 with
      either cGMP or a substrate analog such as sildenafil, each of which is known to
      produce stimulatory effects on enzyme functions, caused a similar native PAGE
      band-shift to the lower mobility form (shift of Band 2 to Band 3). Incubation of
      PDE5 with Mg(++) or Mn(++), which is known to stimulate activity, caused a
      similar shift of the enzyme from Band 2 to Band 3 as did cGMP or sildenafil, but
      incubation with EDTA caused a time- and concentration-dependent shift to higher
      mobility (shift of Bands 2 and 3 to Band 1). A slow time course of the EDTA
      induced band-shift suggested removal of a pre-bound metal ion (Me(++)) with
      affinity of ~0.1 nM, which was similar to the previously determined affinity of
      PDE5 for Zn(++). The EDTA-treated enzyme (Band 1) could be shifted to Bands 2 and
      3 by addition of cGMP, sildenafil, or Me(++); however, the cGMP- or sildenafil
      induced shift was inhibited and the Me(++)-induced shift was facilitated by
      treatment with EDTA. Results suggested that Me(++) removal from PDE5 produces a
      unique apoenzyme form (Band 1, more globular, negatively charged, or both) of
      PDE5 that can be partially converted to forms (Band 2, less globular or
      negatively charged, or both; and Band 3, more elongated/positively charged, or
      both) by addition of Me(++), substrate, or substrate analog. It is concluded that
      Me(++) causes conversion of PDE5 to similar conformational forms as caused by
      substrate or inhibitor binding to the catalytic site.

PMID- 21187143
TI  - Variation in conservation of the cluster for biosynthesis of the phytotoxin
      phaseolotoxin in Pseudomonas syringae suggests at least two events of horizontal
      acquisition.
AB  - Certain strains of Pseudomonas syringae pathovars phaseolicola and actinidiae and
      P. syringae pv. syringae strain CFBP3388 produce the chlorosis-inducing
      phytotoxin phaseolotoxin, which inhibits biosynthesis of arginine and polyamines.
      The 25 kb Pht cluster, responsible for phaseolotoxin biosynthesis, is included in
      a putative pathogenicity island that is nearly identical in selected strains of
      the pathovars phaseolicola and actinidiae, suggesting that it has been recently
      acquired by horizontal transfer. The history of pathogenicity islands is pivotal
      for our understanding of the evolution of virulence in plant pathogenic bacteria;
      nevertheless, our knowledge of the origins, biology and genetics of this island
      is currently rather limited. The aim of this work was to explore the conservation
      of phaseolotoxin biosynthesis genes in a broader collection of isolates and in
      strain CFBP3388, in order to better understand its evolution and gene dynamics.
      PCR, hybridization and sequence analysis showed that the island is highly
      conserved among a diversity of strains of pathovars phaseolicola and actinidiae,
      suggesting that it was acquired only once by each pathovar. Strain CFBP3388
      contained DNA homologous to the Pht cluster, and an insertional mutant in the
      regulatory gene phtL did not synthesize the toxin. A 6.5 kb fragment from strain
      CFBP3388 was syntenic to the Pht cluster, but showed nucleotide identity of only
      85.3%. This contrasts with an identity higher than 99.8% among clusters of
      pathovars phaseolicola and actinidiae, in spite of the fact that pv. syringae is
      phylogenetically closer to pv. phaseolicola. In addition, strain CFBP3388 lacked
      the four integrases that are putatively responsible for the mobility of the
      pathogenicity island. These results indicate that genes for the biosynthesis of
      phaseolotoxin have a complex evolutionary history and were acquired by pathovars
      of P. syringae at least twice during evolution.

PMID- 21187144
TI  - Characterization and cloning of oxygen-tolerant hydrogenase from Klebsiella
      oxytoca HP1.
AB  - Hydrogenase from a hot spring bacterium Klebsiella oxytoca HP1 was purified and
      found to have a specific activity of 199.8 U/mg of protein and a yield of 7.3%.
      The purified enzyme was determined to consist of six subunits (65, 33, 28, 23, 21
      and 18 kDa), similar to hydrogenase-3 from Escherichia coli, and therefore it was
      named Hyd3. The enzyme displayed remarkable oxygen tolerance. For the purified
      enzyme, 50% maximal activity was maintained following incubation for 24 h in air
      at room temperature. The hydrogenase gene cluster (hyc) was cloned and found to
      consist of hycD, hycE, hycF, hycdG, hycH and hycI genes. hycE and hycG genes
      encode for the large and small subunit of the hydrogenase, respectively. A hycE
      gene deletion mutant, DeltahycE, was constructed for elucidating the function of
      the hyc-operon in hydrogen metabolism. Compared with the wild type strain HP1,
      the mutant strain showed a dramatic decrease in hydrogen production in the
      presence of formate, sodium pyruvate and glucose under O(2)-stressed conditions,
      while substantial activity was detected under anaerobic conditions. This strongly
      suggests that K. oxytoca HP1 carries a number of hydrogenases or hydrogen
      metabolic pathways independently of Hyd3. However, Hyd3 is the main factor
      responsible for hydrogen production under O(2) stress conditions.

PMID- 21187145
TI  - Transcriptional analysis of pmeA gene encoding a pectin methylesterase in
      Xanthomonas campestris pv. campestris.
AB  - Exopolysaccharides and several extracellular enzymes of Xanthomonas campestris
      pv. campestris (Xcc), the causative agent of black rot in crucifers, are
      virulence determinants. It is known that Clp (cAMP receptor protein-like protein)
      and RpfF (an enoyl-CoA hydratase homologue required for the synthesis of the
      diffusible signal factor, DSF) regulate production of these factors. In this
      study, plate assay revealed that Xcc possesses pectin methylesterase activity and
      that its expression is controlled by Clp and RpfF. Mutational analysis has
      demonstrated that pmeA encodes a pectin methylesterase. Using the 5' RACE method,
      the pmeA transcription initiation site was mapped. Transcriptional fusion assays
      showed that pmeA transcription is positively regulated by Clp and RpfF, subject
      to catabolite repression which is independent of Clp or RpfF, and repressed under
      conditions of high osmolarity or oxygen limitation. This study not only extends
      previous work on Clp and RpfF regulation by showing that they both influence the
      expression of pmeA in Xcc, but also, for the first time, characterizes pectin
      methylesterase gene expression in Xanthomonas.

PMID- 21187146
TI  - Diversity and ecology of psychrophilic microorganisms.
AB  - Cold environments represent the majority of the biosphere on Earth and have been
      successfully colonized by psychrophilic microorganisms that are able to thrive at
      low temperatures and to survive and even maintain metabolic activity at subzero
      temperatures. These microorganisms play key ecological roles in their habitats
      and include a wide diversity of representatives of all three domains (Bacteria,
      Archaea, Eukarya). In this review, we summarize recent knowledge on the
      abundance, on the taxonomic and functional biodiversity, on low temperature
      adaptation and on the biogeography of microbial communities in a range of aquatic
      and terrestrial cold environments.

PMID- 21187148
TI  - recA730-dependent suppression of recombination deficiency in RecA loading mutants
      of Escherichia coli.
AB  - Homologous recombination is an essential process in double-strand break repair.
      The main requirement for recombination is formation of a RecA filament. Double
      strand breaks can be processed into a RecA filament by the action of three
      enzymatic activities: helicase, 5'-3' exonuclease and RecA loading onto ssDNA.
      These activities are provided by the RecBCD enzyme in wild type cells or by the
      RecF pathway gene products in recBC sbcBC(D) cells. In the recBD1080A mutant
      (recB* mutant), the recombination machineries of RecBCD and RecF pathways are
      interchangeable and include RecB*CD enzyme (helicase), RecJ (5'-3' exonuclease)
      and RecFOR (RecA loading). The mutant RecA730 protein is able to produce a RecA
      filament without the help of RecFOR mediators, since it more efficiently competes
      with SSB protein for ssDNA than the normal RecA protein. It was previously shown
      that the recA730 mutation suppresses UV sensitivity in a uvrA recFOR genetic
      background. We tested whether the recA730 mutation can suppress recombination and
      DNA repair deficiency in a recB* mutant and its derivatives. We show that the
      recA730 mutation suppresses recombination deficiency in a recB* recFOR
      background, where the defect is at the level of RecA loading, but not in the
      recB* recJ background where the defect is at the level of nuclease activity.

PMID- 21187149
TI  - Measuring low levels of protein aggregation by sedimentation velocity.
AB  - The required performance of an analytical method depends on the purpose for which
      it will be used. As a methodology matures, it may find new application, and the
      performance demands placed on the method can increase. Sedimentation velocity
      analytical ultracentrifugation (SV-AUC) has a long and distinguished history with
      important contributions to molecular biology. Now the technique is transitioning
      into industrial settings, and among them, SV-AUC is now used to quantify the
      amount of protein aggregation in biopharmaceutical protein products, often at
      levels less than 1% of the total protein mass. In this paper, we review recent
      advances to SV methodology which have been shown to improve quantitation of
      protein aggregation. Then we discuss the performance of the SV method in its
      current state, with emphasis on the precision and quantitation limit of the
      method, in the context of existing industrial guidance on analytical method
      performance targets for quantitative methods.

PMID- 21187150
TI  - Studying protein degradation pathways in vivo using a cranial window-based
      approach.
AB  - Understanding how specific proteins are degraded by neurons in living animals is
      a fundamental question with relevance to many neurodegenerative diseases.
      Dysfunction in the ubiquitin-proteasome system (UPS) specifically has been
      implicated in several important neurodegenerative diseases including Alzheimer's
      Disease, Parkinson's Disease, and amyotrophic lateral sclerosis. Research in this
      area has been limited by the fact that many inhibitors of the UPS given
      systemically do not cross the blood-brain barrier (BBB) in appreciable levels.
      This limits the ability to easily test in vivo specific hypotheses generated in
      reduced systems, like brain slice or dissociated cell culture, about whether the
      UPS may degrade a particular protein of interest. Although several techniques
      including intracerebral application via direct syringe injection, catheter-pump
      systems and drug-eluting beads are available to introduce BBB-impermeant drugs
      into brain they each have certain limitations and new approaches could provide
      further insights into this problem. In order to test the role of the UPS in
      protein degradation in vivo we have developed a strategy to treat mouse cortex
      with the UPS inhibitor clasto-lactacystin beta-lactone (CLBL) via a "cranial
      window" and recover the treated tissue for immunoblot analysis. This approach can
      be used in several different cranial window configurations including single
      window and double hemi-window arrangements that are tailored for different
      applications. We have also developed two different strategies for recovering
      treated cortical tissue including a vibratome/laser capture microscopy (LCM)
      based and a vibratome only-based approach, each with its own specific advantages.
      We have documented UPS inhibition >600MUm deep into the cortex with this
      strategy. This set of techniques in the living mammalian brain is complementary
      to previously developed approaches and extends the repertoire of tools that can
      be used to the study protein degradation pathways relevant to neurodegenerative
      disease.

PMID- 21187147
TI  - Phylogenetic diversity of bacterial communities in South China Sea mesoscale
      cyclonic eddy perturbations.
AB  - Eddy pumping drives a set of biogeochemical processes by lifting deep waters into
      the euphotic zone. To address the potential effect of such physical processes
      upon the bacterial community, phylogenetic diversity was determined in two cold
      core cyclonic eddies in the South China Sea. 16S rDNA terminal restriction
      fragment length polymorphism analysis of the microbial communities through the
      whole water column showed a wider depth range for the intermediate transition
      water mass at sites inside the eddies than for those outside. This water mass
      contained a relatively more complex community than the euphotic and deep-water
      zones. Stratification of prokaryotic populations between the surface and
      chlorophyll maximum layer of eddy-related sites versus homogeneity of communities
      in the euphotic zone of the reference site, revealed by statistical analysis of
      16S rDNA libraries, is most likely a reflection of isopycnal displacement induced
      by differing water movement inside and outside eddies. Phylogenetic analysis
      revealed that eddy center sites were characterized by deep-water group
      Alteromonadales-affiliated clones, the psychrophilic genus Octadecabacter cluster
      and the nitrogen-fixing phototrophic Rhodospirillaceae cluster, while Paracoccus,
      an important functional group, abundantly existed at the reference site outside
      eddies. Our analysis revealed that bacterial community structure was
      significantly influenced by cyclonic eddy perturbations.

PMID- 21187152
TI  - Assessing mutant huntingtin fragment and polyglutamine aggregation by atomic
      force microscopy.
AB  - Huntington disease (HD), a neurodegenerative disorder, is caused by an expansion
      of more than 35-40 polyglutamine (polyQ) repeats located near the N-terminus of
      the huntingtin (htt) protein. The expansion of the polyQ domain results in the
      ordered assembly of htt fragments into fibrillar aggregates that are the main
      constituents of inclusion bodies, which are a hallmark of the disease. This paper
      describes protocols for studying the aggregation of mutant htt fragments and
      synthetic polyQ peptides with atomic force microscopy (AFM). Ex situ AFM is used
      to characterize aggregate formation in protein incubation as a function of time.
      Methods to quickly and unambiguously distinguish specific aggregate species from
      complex, heterogeneous aggregation reactions based on simple morphological
      features are presented. Finally, the application of time lapse atomic force
      microscopy in solution is presented for studying synthetic model polyQ peptides,
      which allows for tracking the formation and fate of individual aggregates on
      surfaces over time. This ability allows for dynamic studies of the aggregation
      process and direct observation of the interplay between different types of
      aggregates.

PMID- 21187151
TI  - Histidine-tag-directed chromophores for tracer analyses in the analytical
      ultracentrifuge.
AB  - Many recombinant proteins carry an oligohistidine (His(X))-tag that allows their
      purification by immobilized metal affinity chromatography (IMAC). This tag can be
      exploited for the site-specific attachment of chromophores and fluorophores,
      using the same metal ion-nitrilotriacetic acid (NTA) coordination chemistry that
      forms the basis of popular versions of IMAC. Labeling proteins in this way can
      allow their detection at wavelengths outside of the absorption envelopes of un
      modified proteins and nucleic acids. Here we describe use of this technology in
      tracer sedimentation experiments that can be performed in a standard analytical
      ultracentrifuge equipped with absorbance or fluorescence optics. Examples include
      sedimentation velocity in the presence of low molecular weight chromophoric
      solutes, sedimentation equilibrium in the presence of high concentrations of
      background protein and selective labeling to simplify the assignment of species
      in a complex interacting mixture.

PMID- 21187153
TI  - Using Lamm-Equation modeling of sedimentation velocity data to determine the
      kinetic and thermodynamic properties of macromolecular interactions.
AB  - The interaction of macromolecules with themselves and with other macromolecules
      is fundamental to the functioning of living systems. Recent advances in the
      analysis of sedimentation velocity (SV) data obtained by analytical
      ultracentrifugation allow the experimenter to determine important features of
      such interactions, including the equilibrium association constant and information
      about the kinetic off-rate of the interaction. The determination of these
      parameters is made possible by the ability of modern software to fit numerical
      solutions of the Lamm Equation with kinetic considerations directly to SV data.
      Herein, the SV analytical advances implemented in the software package SEDPHAT
      are summarized. Detailed analyses of SV data using these strategies are
      presented. Finally, a few highlights of recent literature reports that feature
      this type of SV data analysis are surveyed.

PMID- 21187154
TI  - Modulatory influence of dopamine receptors on consolidation of object recognition
      memory.
AB  - The role of dopamine receptors in regulating the formation of recognition memory
      remains poorly understood. Here we show the effects of systemic administration of
      dopamine receptor agonists and antagonists on the formation of memory for novel
      object recognition in rats. In Experiment I, rats received an intraperitoneal
      (i.p.) injection of vehicle, the selective D1 receptor agonist SKF38393 (1.0 and
      5.0mg/kg), or the D2 receptor agonist quinpirole (1.0 and 5.0mg/kg) immediately
      after training. In Experiment II, rats received an injection of vehicle, the
      dopamine receptor antagonist SCH23390 (0.1 and 0.05 mg/kg), or the D2 receptor
      antagonist raclopride (0.5 and 0.1mg/kg) before training, followed by an
      injection of vehicle or the nonselective dopamine receptor agonist apomorphine
      (0.05 mg/kg) immediately after training. SKF38393 at 5mg/kg produced an
      enhancement of novel object recognition memory measured at both 24 and 72 h after
      training, whereas the dose of 10mg/kg impaired 24-h retention. Posttraining
      administration of quinpirole did not affect 24-h retention. Apomorphine enhanced
      memory in rats given pretraining raclopride, suggesting that the effect was
      mediated by selective activation of D1 receptors. The results indicate that
      activation of D1 receptors can enhance recognition memory consolidation.
      Importantly, pharmacological activation of D1 receptors enhanced novel object
      recognition memory even under conditions in which control rats showed significant
      retention.

PMID- 21187155
TI  - Local and systemic effects of angiotensin receptor blockade in an emphysema mouse
      model.
AB  - OBJECTIVES: COPD with emphysema causes marked neurohumoral activation.
      Angiotensin II receptors are highly expressed within the lung and interfere with
      mechanisms involved in the progression of emphysema. This study examined the
      effects of an angiotensin II receptor blocker (ARB) on pulmonary and systemic
      manifestations of emphysema in a mouse model. METHODS: Female NMRI mice received
      five intratracheal instillations of porcine pancreatic elastase (emphysema; n =
      11) or phosphate-buffered saline (PBS; n = 4). Emphysema severity was quantified
      histologically by mean linear intercept, exercise tolerance by treadmill running
      distance, and lung biomechanics by compliance. Following emphysema induction, 6
      mice were treated with the ARB irbesartan for 8 weeks, while 5 mice receiving
      standard food served as controls. RESULTS: Following emphysema induction, mean
      linear intercept was higher in elastase-treated than in PBS-treated lungs (103.0
      +/- 6.2 MUm vs. 35.0 +/- 0.6 MUm; p = 0.043) while running distance was shorter
      in emphysema mice (418.6 +/- 83.5 m vs. 906.6 +/- 244.6 m, p = 0.028). Irbesartan
      treated emphysema mice showed a lower mean linear intercept (90.8 +/- 3.8 MUm vs.
      121.5 +/- 8.1 MUm; p = 0.005), improved compliance (163.6 +/- 55.9 MUl/cmH(2)O
      vs. 354.4 +/- 72.5 MUl/cmH(2)O; p = 0.063) and greater running distance (p ANOVA
      = 0.015) compared to emphysema mice receiving standard food. CONCLUSIONS: The ARB
      irbesartan elicits encouraging beneficial effects on emphysema severity, lung
      biomechanics and exercise capacity in an emphysema mouse model. These findings
      might help to understand the corresponding positive effects of angiotensin II
      receptor blockade noticed in patients with COPD.

PMID- 21187156
TI  - Association of ex vivo vascular and bronchial dysfunctions in smokers.
AB  - BACKGROUND: It has recently been shown that systemic endothelial dysfunction is
      associated with airflow limitation in COPD. We conducted this ex vivo study to
      assess whether endothelial dysfunction of pulmonary arteries of former smokers
      was associated with modifications of airway functions. METHODS: Pharmacological
      experiments were conducted on arterial and bronchial rings obtained from lung
      specimen of 20 patients: 13 smokers without COPD and 7 smokers with mild to
      moderate COPD (GOLD class I or II). The impairment of acetylcholine-mediated
      vasodilation (constriction) of preconstricted arterial rings defined endothelial
      dysfunction. Resting tone (initial and after a contraction test) and cGMP
      mediated dilation of bronchial rings in response to zaprinast were evaluated.
      RESULTS: Initial airway resting tone was correlated with airflow limitation
      (FEV(1) % predicted: Rho = -0.49; p = 0.032). The acetylcholine response of
      arterial rings was correlated with zaprinast-induced bronchodilation (Rho = 0.54,
      p = 0.019). Patients with endothelial dysfunction (n = 5), as compared with those
      displaying no dysfunction (n = 15), were characterized by an increased resting
      tone (after contraction test), an impaired response to zaprinast but a similar
      degree of airflow limitation (FEV(1)). CONCLUSION: Endothelial dysfunction of
      pulmonary arteries is associated with increased resting tone and impaired cGMP
      mediated dilation of airways in former smokers, suggesting common underlying
      mechanisms of pulmonary arterial and bronchial dysfunctions.

PMID- 21187158
TI  - Early phase TGFbeta receptor signalling dynamics stabilised by the deubiquitinase
      UCH37 promotes cell migratory responses.
AB  - TGFbeta signals through serine/threonine kinase receptors and intracellular Smad
      transcription factors. An important regulatory step involves ubiquitination of
      Smads and/or TGFbeta receptors by specific ubiquitin ligases, in a process that
      can be reversed by the deubiquitinating enzyme UCH37. Here, to explore the
      physiological role of UCH37 in TGFbeta signalling we have generated stable and
      inducible HaCAT keratinocyte and Colo-357 pancreatic carcinoma cell lines mis
      expressing UCH37. We show that UCH37 knockdown significantly inhibits the
      activity of a TGFbeta-dependent gene reporter and selectively decreases levels of
      some TGFbeta-dependent target genes, notably p21 and PAI-1, but only during the
      early phase of TGFbeta receptor activation. Interestingly, UCH37 knockdown in
      Colo-357 cells had no effect on TGFbeta-dependent cell proliferation and
      epithelial-mesenchymal transition, yet significantly impaired cell migration.
      Collectively, our data indicate that UCH37 sustains early TGFbeta pathway
      activation kinetics that determines threshold-specific gene expression patterns,
      and that opposing actions of ubiquitin ligases and deubiquitinases influences
      distinct biological TGFbeta-dependent biological responses. Moreover, we suggest
      that UCH37 could represent a viable target for novel and selective cancer
      therapeutics.

PMID- 21187157
TI  - Activation of a non-genomic Pim-1/Bad-Pser75 module is required for an efficient
      pro-survival effect of Bcl-xL induced by androgen in LNCaP cells.
AB  - The present report investigated the pathway(s) involved in the inhibition of
      apoptosis by the synthetic androgen, R1881 in serum-starved LNCaP cells exposed
      to the pi3K inhibitor, LY294002. R1881 blocked LY294002-induced apoptosis through
      the inhibition of Bak activation via an increase in Bcl-xL transcription and
      protein expression. In addition, R1881 treatment enhanced the stability of the
      Pim-1 kinase, resulting in the inhibition of the activation of the BH3-only
      protein Bad through its phosphorylation at ser75. Pharmacological inhibition of
      the Pim-1 kinase activity with quercetagetin, a highly selective Pim-1 inhibitor,
      prevented R1881-mediated increase in Bad phosphorylation and restored cell
      sensitivity to LY294002-induced apoptosis despite the increase in Bcl-xL
      expression. These results demonstrate for the first time that the inhibition of
      LY294002-induced apoptosis by androgen is a function of an androgen receptor
      dependent genomic signaling pathway leading to an increase in Bcl-xL expression
      as well as a non-genomic, Pim-1-dependent, signaling pathway mediated via
      phosphorylation of Bad at ser75.

PMID- 21187159
TI  - ZNF224: Structure and role of a multifunctional KRAB-ZFP protein.
AB  - The Kruppel-like zinc finger protein ZNF224 was originally identified as the
      transcriptional repressor of the human aldolase A gene. ZNF224 transcriptional
      repression depends on interaction with the corepressor KAP-1 and the recruitment
      of enzyme activities modifying chromatin, in accordance with repression mechanism
      of KRAB-ZFP family. Recently, the arginine methyltransferase PRMT5 was
      demonstrated to play a crucial role in the transcriptional ZNF224 repressor
      complex. An alternatively spliced isoform, ZNF255, arises from the ZNF224 gene.
      ZNF224 and ZNF255 have a distinct pattern of distribution within the cell and
      display a specific pattern of interaction with different molecular partners.
      These isoform-specific interactions seem to control different cellular pathways.
      These findings suggest that ZNF224 is a multifunctional protein and that
      alternative splicing, sub-cellular compartmentalization and isoform-specific
      interactions may modulate its activity.

PMID- 21187160
TI  - Interactions between normal and transformed epithelial cells: Their contributions
      to tumourigenesis.
AB  - During the initial stages of carcinogenesis, neoplastic transformation occurs in
      single epithelial cells and the transformed cells proliferate while being
      surrounded by normal epithelia. In Drosophila, normal and transformed epithelial
      cells compete with each other for survival, a process called cell competition.
      However, it was not known whether comparable phenomena also occur in mammals.
      Recently, several reports have shown that the interaction between normal and
      transformed epithelial cells causes various phenomena in mammals. For example,
      with elaborate cell culture systems that express oncoproteins or knockdown tumour
      suppressor proteins in an inducible manner, certain types of transformed cells
      have been shown to be apically eliminated from normal epithelial layers in an
      apoptosis-dependent or -independent manner. During the process of apical
      extrusion, various signalling pathways are modulated in transformed cells located
      within the normal epithelium, indicating that the presence of surrounding normal
      epithelial cells affects the behaviour and fate of transformed cells. Recent
      studies in mice have also shown that normal and transformed cells can compete
      with each other for survival during several processes such as liver regeneration.
      In this review, we will introduce these recent publications on interactions
      between normal and transformed mammalian epithelial cells. Furthermore, we will
      discuss how these studies can potentially lead to identification of biomarkers
      for precancerous cells and to invention of novel types of cancer prevention and
      treatment.

PMID- 21187161
TI  - Total Ginsenosides suppress the neointimal hyperplasia of rat carotid artery
      induced by balloon injury.
AB  - Ginsenosides, the active components found in Panax ginseng, have been reported to
      inhibit the cardiac hypertrophy in rats. This study aims to observe the potential
      effect of total ginsenosides (TG) on the hypertrophic vascular diseases. The
      model of vascular neointimal hyperplasia was established by rubbing the
      endothelia of the common carotid artery with a balloon in male Sprague Dawley
      rats. TG (15 mg/kg/day, 45 mg/kg/day), L-arginine (L-arg) 200 mg/kg/day, and NG
      nitro-L-arginine-methyl ester (L-NAME) 100 mg/kg/day used with the same dose of L
      arg or TG 45 mg/kg/day were given for 7 and 14 consecutive days after surgery. TG
      and L-arg administrations significantly ameliorated the histopathology of injured
      carotid artery, which was abolished or blunted by L-NAME, an NOS inhibitor; TG
      and L-arg could also remarkably reduce the expression of proliferating cell
      nuclear antigen (PCNA), a proliferation marker of vascular smooth muscle
      cells(VSMCs), in neointima of the injured artery wall. Further study indicated
      that balloon injury caused a decreased superoxide dismutase (SOD) activity and an
      elevated malondialdehyde (MDA) content in plasma, and reduced the cGMP level in
      the artery wall, which were reversed by TG. It was concluded that TG suppress the
      rat carotid artery neointimal hyperplasia induced by balloon injury, which may be
      involved in its anti-oxidative action and enhancing the inhibition effects of
      NO/cGMP on VSMC proliferation.

PMID- 21187163
TI  - IRINI: random group allocation of multiple prognostic factors.
AB  - Statistically sound experimental design in pharmacology studies ensures that the
      known prognostic factors, if any, are equally represented across investigational
      groups to avoid bias and imbalance which could render the experiment invalid or
      lead to false conclusions. Complete randomization can be effective to reduce bias
      in the created groups especially in large sample size situations. However, in
      small studies which involve only few treatment subjects, as in preclinical
      trials, there is a high chance of imbalance. The effects of this imbalance may be
      removed through covariate analysis or prevented with stratified randomization,
      however small studies limit the number of covariates to be analyzed this way. The
      problem is accentuated when there are multiple baseline covariates with varying
      scales and magnitudes to be considered in the randomization, and creating a
      balanced solution becomes a combinatorial challenge. Our method, IRINI, uses an
      optimization technique to achieve treatment to subject group allocation across
      multiple prognostic factors concurrently. It ensures that the created groups are
      equal in size and statistically comparable in terms of mean and variance. This
      method is a novel application of genetic algorithms to solve the allocation
      problem and simultaneously ensure quality, speed of the results and randomness of
      the process. Results from preclinical trials demonstrate the effectiveness of the
      method.

PMID- 21187164
TI  - Minimization does not by its nature preclude allocation concealment and invite
      selection bias, as Berger claims.

PMID- 21187165
TI  - Fibroblast immuno-diagnosis of cytochrome oxidase (COX) deficiency in
      mitochondrial disease.
AB  - We studied cytochrome c oxidase (COX) expression patterns in nuclear and mtDNA
      gene defects. Using quantitative immunocytochemical assay for COX, heteroplasmic
      staining was seen in MELAS patients with mtDNA mutations but similar staining
      variability was seen in control cell lines and nuclear gene defects. All
      fibroblast lines showed a wide variability in cell-to-cell COX I staining
      intensity. All 8 patient fibroblast lines had reduced COX staining on
      immunocytochemistry. In 6 lines reduced protein amount was seen on Western
      blotting and 7 had low COX activity. This study demonstrates that nuclear gene
      defects can produce a heteroplasmic appearance on immunocytochemistry.

PMID- 21187166
TI  - N-(2-mercaptopropionyl)-glycine but not allopurinol prevented cigarette smoke
      induced alveolar enlargement in mouse.
AB  - We investigated the possible protective effects of the Allopurinol (A), N-(2
      mercaptopropionyl)-glycine (M) and N-acetylcysteine (N) against lung injury
      caused by long-term exposure to cigarette smoke (CS) in mouse. C57BL6 mice were
      exposed to 12 cigarettes a day for 60 days and concomitantly treated with either
      one of the antioxidant drugs diluted in saline (CS+A-50 mg/kg; CS+M-200
      mg/kg/day; CS+N-200 mg/kg/day). Control groups were sham-smoked (AA). Long-term
      CS exposure results in extensive parenchyma destruction in CS group. Both CS+N
      and CS+M groups showed preserved alveolar structure and showed preserved lung
      function when compared to CS group. Macrophage and neutrophil counts were
      decreased in CS+M, and CS+N groups when compared to CS group (p<0.05).
      Antioxidant enzyme activities were reduced in all treated groups. CS+A showed the
      highest reduction in catalase activity (-25%, p<0.01). We conclude that M
      treatment reduced long-term CS-induced inflammatory lung parenchyma destruction
      and lung function, comparable to N treatment, however, antioxidant administration
      did not reverse CS-induced antioxidant enzyme activity reduction.

PMID- 21187167
TI  - Tight junction proteins contribute to barrier properties in human pleura.
AB  - The permeability of pleural mesothelium helps to control the volume and
      composition of the liquid lubricating pleural surfaces. Information on pleural
      barrier function in health and disease, however, is scarce. Tissue specimens of
      human pleura were mounted in Ussing chambers for measurement of transmesothelial
      resistance. Expression of tight junction (TJ) proteins was studied by Western
      blots and immune fluorescence confocal microscopy. Both visceral and parietal
      pleura showed barrier properties represented by transmesothelial resistance.
      Occludin, claudin-1, -3, -5, and -7, were detected in visceral pleura. In
      parietal pleura, the same TJ proteins were detected, except claudin-7. In tissues
      from patients with pleural inflammation these tightening claudins were decreased
      and in visceral pleura claudin-2, a paracellular channel former, became apparent.
      We report that barrier function in human pleura coincides with expression of
      claudins known to be key determinants of epithelial barrier properties. In
      inflamed tissue, claudin expression indicates a reduced barrier function.

PMID- 21187168
TI  - Degradation studies on highly oriented poly(glycolic acid) fibres with different
      lamellar structures.
AB  - Highly oriented poly(glycolic acid) (PGA) fibres with an initial tensile strength
      of 1.1 GPa and different lamellar morphologies were prepared and studied during
      degradation in aqueous media at 37 degrees C. A combination of small- and wide
      angle X-ray scattering was used to study the structural changes during
      degradation and to generate two structural models of highly oriented PGA fibres
      with different lamellar morphologies. It is shown that as a result of
      crystallisation during degradation PGA crystals grow preferentially along the
      (110) and (020) directions of the crystal lattice or perpendicular to the
      orientation direction of the fibres. (1)H nuclear magnetic resonance measurements
      revealed three phases within the fibres with different relaxation times: (1) a
      mobile amorphous phase with a short relaxation time; (2) a semi-rigid phase with
      an intermediate relaxation time; (3) a rigid crystalline phase with a longer
      relaxation time. It is shown that the mobile amorphous phase degrades very
      rapidly and that it plays only a small role in the tensile mechanical behaviour
      of the fibres during degradation. It is shown that semi-rigid chains connecting
      crystalline domains are responsible for transferring the stress between
      crystalline domains and carrying the tensile deformation. It is proposed that
      once these tie molecules degrade considerably the oriented fibres very rapidly
      lose their strength retention.

PMID- 21187169
TI  - Amino-modified silica surfaces efficiently immobilize bone morphogenetic protein
      2 (BMP2) for medical purposes.
AB  - Due to its ability to induce de novo bone formation the differentiation factor
      bone morphogenetic protein 2 (BMP2) is often used to enhance the integration of
      bone implants. With the aim of reducing possible high dose side-effects and to
      lower the costs, in order to produce affordable implants, we developed a simple
      and fast method for the immobilization of BMP2 on silica-based surfaces using
      silane linkers which carry amino or epoxy functions. We put an especial emphasis
      on the influence of the nanoscale surface topography of the silica layer.
      Therefore, we chose glass (for control experiments) and Bioverit(r) II (as a
      typical implant base material) as support materials and coated these substrates
      with unstructured or nanoporous amorphous silica layers for comparison.
      Immobilized BMP2 was quantified by two different methods: by ELISA and by a cell
      based assay for active BMP2. These tests probe for immunologically and
      biologically active BMP2, respectively. The results show that the amino
      functionalization is better suited for immobilizing the protein. Strikingly, a
      considerably higher amount of BMP2 could be immobilized on coated Bioverit(r) II
      surfaces compared with coated glass substrates, which was presumably due to the
      macroscopic roughness of the Bioverit(r) II substrates. In addition, it was found
      that the nanoporous silica coatings on Bioverit(r) II substrates were able to
      bind more BMP2 than the unstructured ones.

PMID- 21187170
TI  - Thermoresponsive, in situ cross-linkable hydrogels based on N
      isopropylacrylamide: fabrication, characterization and mesenchymal stem cell
      encapsulation.
AB  - Hydrogels that solidify in response to a dual, physical and chemical, mechanism
      upon temperature increase were fabricated and characterized. The hydrogels were
      based on N-isopropylacrylamide, which renders them thermoresponsive, and
      contained covalently cross-linkable moieties in the macromers. The effects of the
      macromer end group, acrylate or methacrylate, and the fabrication conditions on
      the degradative and swelling properties of the hydrogels were investigated. The
      hydrogels exhibited higher swelling below their lower critical solution
      temperature (LCST). When immersed in cell culture medium at physiological
      temperature, which was above their LCST, hydrogels showed constant swelling and
      no degradation over 8 weeks, with the methacrylated hydrogels showing greater
      swelling than their acrylated analogs. In addition, hydrogels immersed in cell
      culture medium under the same conditions showed lower swelling compared with
      phosphate-buffered saline. The interplay between chemical cross-linking and
      thermally induced phase separation affected the swelling characteristics of the
      hydrogels in different media. Mesenchymal stem cells encapsulated in the
      hydrogels in vitro were viable over 3 weeks and markers of osteogenic
      differentiation were detected when the cells were cultured with osteogenic
      supplements. Hydrogel mineralization in the absence of cells was observed in cell
      culture medium with the addition of fetal bovine serum and beta-glycerol
      phosphate. The results suggest that these hydrogels may be suitable as carriers
      for cell delivery in tissue engineering.

PMID- 21187171
TI  - Biodegradable functional poly(ester amide)s with pendant hydroxyl functional
      groups: synthesis, characterization, fabrication and in vitro cellular response.
AB  - The synthesis of a new family of biodegradable alpha-amino acid poly(ester
      amide)s (AA-PEAs) with pendant benzyl ether groups and hydroxyl functional groups
      is reported. The synthetic strategy employs the ring opening reaction of O-benzyl
      L-serine-N-carboxyanhydride with di-p-toluenesulfonic acid salts of bis-L-valine
      butane-1,4-diester, followed by solution polycondesation reactions with di-p
      nitrophenyl sebacate in N,N-dimethylacetamide. Catalytic hydrogenation of the
      resulting benzyl ether protected AA-PEAs (PEA-Ser-Bzs) was performed to restore
      the hydroxyl functional groups in the functionalized AA-PEAs (PEA-Ser-OH). All
      resulting polymers were characterized by standard physico-chemical methods. The
      pendant hydroxyl groups in PEA-Ser-OH were used to fabricate AA-PEA-based gels
      via acrylation and photo-gelation. The cell-polymer interactions of PEA-Ser-Bz
      and PEA-Ser-OH were evaluated in terms of cell attachment and proliferation assay
      using bovine aortic endothelial cells (BAECs) as well as fibroblasts. The cell
      culture data indicated that the hydrophobic/hydrophilic characteristics (from
      contact angle data) of these AA-PEAs could significantly affect the interaction
      between BAECs and AA-PEA. This finding may provide additional possible
      applications for this new family of functionalized AA-PEA polymers.

PMID- 21187172
TI  - On the role of the filament length distribution in the mechanics of semiflexible
      networks.
AB  - This paper explores the effects of filament length polydispersity on the
      mechanical properties of semiflexible crosslinked polymer networks. Extending
      previous studies on monodisperse networks, we compute numerically the response of
      crosslinked networks of elastic filaments of bimodal and exponential length
      distributions. These polydisperse networks are subject to the same affine to
      nonaffine (A/NA) transition observed previously for monodisperse networks,
      wherein the decreases in either crosslink density or bending stiffness lead to a
      shift from affine, stretching-dominated deformations to nonaffine, bending
      dominated deformations. We find that the onset of this transition is generally
      more sensitive to changes in the density of longer filaments than shorter
      filaments, meaning that longer filaments have greater mechanical efficiency.
      Moreover, in polydisperse networks, mixtures of long and short filaments interact
      cooperatively to generally produce a nonaffine mechanical response closer to the
      affine prediction than comparable monodisperse networks of either long or short
      filaments. Accordingly, the mechanical affinity of polydisperse networks is
      dependent on the filament length composition. Overall, length polydispersity has
      the effect of sharpening and shifting the A/NA transition to lower network
      densities. We discuss the implications of these results on experimental
      observation of the A/NA transition, and on the design of advanced materials.

PMID- 21187173
TI  - Enhanced attachment, growth and migration of smooth muscle cells on microcarriers
      produced using thermally induced phase separation.
AB  - Microcarriers are widely used for the expansion of cells in vitro, but also offer
      an approach for combining cell transplantation and tissue bulking for
      regenerative medicine in a minimally invasive manner. This could be beneficial in
      conditions associated with muscle damage or atrophy, such as faecal incontinence,
      where the use of bulking materials or cell transplantation alone has proven to be
      ineffective. Microcarriers currently available have not been designed for this
      purpose and are likely to be suboptimal due to their physical and biochemical
      properties. The aim of this study was to investigate macroporous microspheres of
      polylactide-co-glycolide (PLGA), prepared using a thermally induced phase
      separation technique, for their suitability as cell microcarriers for the
      transplantation of smooth muscle cells. Cell attachment, growth and migration
      were studied and compared with commercially available porcine gelatin
      microcarriers (Cultispher-S) in suspension culture. Smooth muscle cells attached
      more rapidly to the PLGA microcarriers, which also significantly enhanced the
      rate of cell growth compared with Cultispher-S microcarriers. The majority of
      smooth muscle cells attached to the PLGA microcarriers in suspension culture were
      able to migrate away over a 15 day period of static culture, unlike Cultispher-S
      microcarriers which retained the majority of cells. The ability of PLGA
      microcarriers to enhance cell growth combined with their capacity to release
      cells at the sites of delivery are features that make them ideally suited for use
      as a cell transplantation delivery device in tissue engineering and regenerative
      medicine.

PMID- 21187174
TI  - Factors associated with positive outcomes in 131 patients treated with gauze
      based negative pressure wound therapy.
AB  - Negative Pressure Wound Therapy (NPWT) is commonly used in many surgical
      specialties to improve wound management and healing outcomes. This study reports
      the ability of gauze-based NPWT to address several treatment goals commonly
      defined at the onset of therapy. A prospective, multi-center, non-comparative
      clinical investigation was carried out using gauze-based NPWT in chronic and
      acute wounds. 131 patients including traumatic, post-surgical and chronic wounds
      were assessed. Weekly percentage reductions in wound area, depth and volume were
      8.3%, 15.8% and 20.5% respectively (p < 0.001). A reduction in exudate level was
      observed from baseline to treatment discontinuation (p < 0.001). An increase (p =
      0.007) in red granulation tissue and a decrease (p < 0.001) in non-viable tissue
      was observed. Baseline wound characteristics associated with slower rates of
      progress included chronic wound aetiologies, longer wound duration prior to NPWT
      and presence of diabetes as a co-morbidity. Important indicators of wounds which
      had improved sufficiently and no longer required NPWT included reduction in
      volume and exudate levels. Gauze-based NPWT can be used to address many of the
      treatment goals commonly defined at the onset of therapy including reduction in
      wound volume, management of exudate and infection status, and improvement in
      wound bed quality.

PMID- 21187175
TI  - Diagnosis of distal 22q11.2 deletion syndrome in a patient with a
      teratoid/rhabdoid tumour.
AB  - We report an 18 year old patient with mild intellectual disability who was
      diagnosed with a late onset teratoid/rhabdoid tumour by histological and
      immunohistochemical studies. Array-CGH studies, performed on a peripheral blood
      sample, showed a 3.4Mb deletion of chromosome 22q11.2, distal to the common
      DiGeorge syndrome (DGS) or Velocardiofacial syndrome (VCFs) region. This deletion
      is consistent with a diagnosis of distal 22q11.2 deletion syndrome. The deletion
      encompasses the INI1/SMARCB1 tumour suppressor gene. Biallelic inactivation of
      this gene is characteristic of atypical teratoid/rhabdoid tumours. Although
      several constitutional chromosome conditions are known to have increased
      susceptibility to various forms of cancer, very little is known regarding the
      magnitude of risk for malignancy associated with distal 22q11.2 deletion
      syndrome. In view of this finding we suggest that patients diagnosed with distal
      22q11.2 deletion syndrome undergo careful prolonged monitoring for this type of
      tumour. This case demonstrates the need to carefully assess regions found to be
      deleted in individuals, referred for dysmorphia and/or developments delay, by
      array-CGH for the presence of genes known to be implicated in malignancy.

PMID- 21187176
TI  - 15q11.2 microdeletion - seven new patients with delayed development and/or
      behavioural problems.
AB  - 15q11.2 microdeletion has been suggested as a new microdeletion syndrome and
      several patients have been described in the literature. We report seven new
      patients belonging to six families, age 9-24 years old, with a 350 kb 15q11.2
      deletion of the four highly conserved genes (TUBGCP5, NIPA1, NIPA2 and CYFIP1)
      earlier reported. All our patients had some degree of learning difficulties,
      delayed development and/or behavioural problems. Common dysmorphic features and
      congenital malformations were not characteristics of our patients. The deletion
      was inherited from a mildly affected parent in all cases tested (5/6 families
      available for testing both parents). These seven new cases confirm some of the
      features earlier reported to be associated with 15q11.2 deletion, and help to
      further delineate the phenotype associated with 15q11.2 deletion.

PMID- 21187177
TI  - Antibody responses after intravaginal immunisation with trimeric HIV-1 CN54 clade
      C gp140 in Carbopol gel are augmented by systemic priming or boosting with an
      adjuvanted formulation.
AB  - Optimum strategies to elicit and maintain antibodies at mucosal portals of virus
      entry are critical for the development of vaccines against human immunodeficiency
      virus (HIV). Here we show in non-human primates that a novel regimen of repeated
      intravaginal delivery of a non-adjuvanted, soluble recombinant trimeric HIV
      1(CN54) clade C envelope glycoprotein (gp140) administered in Carbopol gel can
      prime for B-cell responses even in the absence of seroconversion. Following 3
      cycles of repeated intravaginal administration, throughout each intermenses
      interval, 3 of 4 macaques produced or boosted systemic and mucosally-detected
      antibodies upon intramuscular immunisation with gp140 formulated in AS01
      adjuvant. Reciprocally, a single intramuscular immunisation primed 3 of 4
      macaques for antibody boosting after a single cycle of intravaginal immunisation.
      Virus neutralising activity was detected against clade C and clade B HIV-1
      envelopes but was restricted to highly neutralisation sensitive pseudoviruses.

PMID- 21187181
TI  - You only have to exercise on the days that you eat.

PMID- 21187179
TI  - Nafamostat mesilate attenuates colonic inflammation and mast cell infiltration in
      the experimental colitis.
AB  - Serine proteases are important in the pathogenesis of intestinal inflammation.
      Recent studies have shown that nafamostat mesilate (NM) can inhibit the colonic
      mucosal inflammation induced by TNBS in rats. The aim of this study was to
      investigate the anti-inflammatory effects of NM on a DSS-induced colitis. Colitis
      was induced in female BALB/c mice by 5% dextran sulfate sodium (DSS) for 6 days.
      NM (2 or 20mg/kg body weight) was orally administered once a day for 6 days
      during treatment of the mice with DSS. The inflammatory response of the colon was
      assessed 1 week after DSS treatment. NM at a high dose, but not at a low dose
      significantly decreased disease activity index (DAI) and myeloperoxidase (MPO)
      induced by DSS. Furthermore, NM (20mg/kg) inhibited the production of tumor
      necrosis factor (TNF)-alpha, cyclooxygenase-2 (COX-2) and inducible nitric oxide
      synthase (iNOS) in the colonic tissues treated with DSS. The increase in chymase
      activity by DSS treatment was also attenuated by the administration of NM
      (20mg/kg). NM (20mg/kg) significantly decreased the colonic mucosal injury and
      the infiltrated mast cell number induced by DSS. These results indicate that NM
      might inhibit the colonic inflammation through inhibition of both chymase
      activity and mast cell infiltration in colon tissues of DSS-induced colitis.

PMID- 21187182
TI  - Renin Angiotensin Aldosterone System Blockade: Little to No Rationale for ACE
      Inhibitor and ARB Combinations.
AB  - Our understanding of the complexities and inter-related pathways of the renin
      angiotensin-aldosterone system continues to evolve. Which drugs to use, when, and
      how, are everyday questions faced by clinicians in the ambulatory setting.
      Combining these classes, for the purpose of enhancing renin-angiotensin
      aldosterone system blockade and incremental blood pressure, nephroprotective, and
      cardioprotective effects, logically has emerged as an area for scientific inquiry
      and clinical use. Despite the lack of evidence on safety and efficacy in most
      disease states, dual therapy has been embraced as a treatment option. Most
      studies of angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor
      blocker (ARB) combination therapy in the treatment of hypertension have
      limitations. In contrast, combination ACE inhibitor-ARB therapy in systolic heart
      failure has been addressed in several large randomized controlled trials. Until
      recently, there has been limited and conflicting evidence for the use of
      combination therapy for the prevention or management of nephropathy. Based on the
      new evidence, combination ACE inhibitor-ARB therapy in the treatment and
      management of hypertension, heart failure, and nephropathy should be limited.

PMID- 21187178
TI  - Identifying long-term memory B-cells in vaccinated children despite waning
      antibody levels specific for Bordetella pertussis proteins.
AB  - Whooping cough is a respiratory disease caused by Bordetella pertussis. Since the
      1950s in developed countries pertussis vaccinations are included in the national
      immunization program. However, antibody levels rapidly wane after both whole cell
      and acellular pertussis vaccination. Therefore protection against pertussis may
      depend largely on long-term B- and T-cell immunities. We investigated long-term
      pertussis-specific memory B-cell responses in children who were primed at infant
      age with the Dutch wP-vaccine (ISRCTN65428640). Purified B-cells were
      characterized by FACS-analysis and after polyclonal stimulation memory B-cells
      were detected by ELISPOT-assays specific for pertussis toxin, filamentous
      haemagglutinin, pertactin and tetanus. In addition, plasma IgG levels directed to
      the same antigens were measured by a fluorescent bead-based multiplex
      immunoassay. Two and 3 years after wP priming as well as 2 and 5 years after the
      aP booster at the age of 4, low plasma IgG levels to the pertussis proteins were
      found. At the same time, however pertussis protein-specific memory B-cells could
      be detected and their number increased with age. The number of tetanus-specific
      memory B-cells was similar in all age groups, whereas IgG-tetanus levels were
      high 2 years after tetanus booster compared to pre- and 5 years post-booster
      levels. This study shows the presence of long-term pertussis protein-specific
      memory B-cells in children despite waning antibody levels after vaccination,
      which suggests that memory B-cells in addition to antibodies may contribute to
      protection against pertussis.

PMID- 21187183
TI  - Rare and deadly.

PMID- 21187184
TI  - Recent trends in the incidence, treatment, and outcomes of patients with STEMI
      and NSTEMI.
AB  - BACKGROUND: despite the widespread use of electrocardiographic changes to
      characterize patients presenting with acute myocardial infarction, little is
      known about recent trends in the incidence rates, treatment, and outcomes of
      patients admitted for acute myocardial infarction further classified according to
      the presence of ST-segment elevation. The objectives of this population-based
      study were to examine recent trends in the incidence and death rates associated
      with the 2 major types of acute myocardial infarction in residents of a large
      central Massachusetts metropolitan area. METHODS: We reviewed the medical records
      of 5383 residents of the Worcester (MA) metropolitan area hospitalized for either
      ST-segment elevation acute myocardial infarction (STEMI) or non-ST-segment acute
      myocardial infarction (NSTEMI) between 1997 and 2005 at 11 greater Worcester
      medical centers. RESULTS: the incidence rates (per 100,000) of STEMI decreased
      appreciably (121 to 77), whereas the incidence rates of NSTEMI increased slightly
      (126 to 132) between 1997 and 2005. Although in-hospital and 30-day case-fatality
      rates remained stable in both groups, 1-year postdischarge death rates decreased
      between 1997 and 2005 for patients with STEMI and NSTEMI. CONCLUSIONS: the
      results of this study demonstrate recent decreases in the magnitude of STEMI,
      slight increases in the incidence rates of NSTEMI, and decreases in long-term
      mortality in patients with STEMI and NSTEMI. Our findings suggest that acute
      myocardial infarction prevention and treatment efforts have resulted in favorable
      decreases in the frequency of STEMI and death rates from the major types of acute
      myocardial infarction.

PMID- 21187185
TI  - Race, Bleeding, and Outcomes in STEMI Patients Treated with Fibrinolytic Therapy.
AB  - BACKGROUND: studies have shown higher bleeding and mortality rates among African
      Americans who receive fibrinolytic therapy for ST-segment elevation myocardial
      infarction (STEMI) compared with whites; however, the relationship of bleeding
      risk to mortality has not been evaluated. METHODS: we studied data from 32,260
      STEMI patients receiving fibrinolysis enrolled in the US in 5 clinical trials.
      Bleeding was defined according to criteria from the Global Utilization of
      Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries
      study. Main outcome measure was adjusted 1-year mortality. RESULTS: despite
      younger age (median: 57 years vs 61 years) and fewer comorbidities, moderate or
      severe bleeding occurred more frequently among African-Americans than whites
      (16.3% vs 14.1%; P=.0147, adjusted OR 1.36; 95% confidence interval [CI], 1.14
      1.62; P=.0006) as did 1-year mortality (11.5% vs 9.4%). African-American race and
      moderate or severe bleeding were independently related to 1-year mortality
      (chi(2) 9.02, P=.0003 and 148.58, P<.0001, respectively). Mortality was highest
      among African Americans with bleeding (hazard ratio [HR] 2.83; 95% CI, 2.08-3.86)
      followed by whites with bleeding (HR 1.99; 95% CI, 1.78-2.22) and African
      Americans without bleeding (HR 1.33; 95% CI, 1.02-1.73) (referent whites without
      bleeding). CONCLUSIONS: in STEMI patients receiving fibrinolysis, moderate or
      severe bleeding and mortality were significantly higher in African Americans
      compared with whites. Bleeding was associated with similarly increased mortality
      risk in both groups.

PMID- 21187186
TI  - Venous thromboembolism with chronic liver disease.
AB  - BACKGROUND: patients with chronic liver disease have both antithrombotic and
      prothrombotic coagulation abnormalities. Published data conflict on whether
      patients with chronic liver disease have a high or low prevalence of venous
      thromboembolism. METHODS: the number of patients discharged from hospitals
      throughout the US with a diagnostic code for chronic alcoholic and chronic
      nonalcoholic liver disease from 1979 through 2006 was obtained from the National
      Hospital Discharge Survey. We compared prevalences of venous thromboembolism
      among patients with chronic alcoholic liver disease and chronic nonalcoholic
      liver disease. RESULTS: among 4,927,000 hospitalized patients with chronic
      alcoholic liver disease from 1979-2006, the prevalence of venous thromboembolism
      was 0.6%, compared with 0.9% among 4,565,000 hospitalized patients with chronic
      nonalcoholic liver disease. CONCLUSION: the prevalence of venous thromboembolism
      in hospitalized patients with chronic liver disease, both alcoholic and
      nonalcoholic, was low. The prevalence of venous thromboembolism was higher in
      those with chronic non-alcoholic liver disease, but the difference was small and
      of no clinical consequence. Based on the literature, both showed a lower
      prevalence of venous thromboembolism than in hospitalized patients with most
      other medical diseases. It may be that both chronic alcoholic liver disease and
      chronic nonalcoholic liver disease have protective antithrombotic mechanisms,
      although the mechanisms differ.

PMID- 21187187
TI  - Hyperinsulinemia and the development of nonalcoholic Fatty liver disease in
      nondiabetic adults.
AB  - BACKGROUND: insulin resistance is known to be the most important pathogenic
      factor in the development of nonalcoholic fatty liver disease. We performed a
      prospective study to analyze the associations of baseline and changes in fasting
      insulin levels with future development of nonalcoholic fatty liver disease in
      nondiabetic adults over a 5-year period. METHODS: this study was performed in
      4954 subjects who did not have diabetes or nonalcoholic fatty liver disease and
      who participated in a health checkup program in both 2003 and 2008. The presence
      of nonalcoholic fatty liver disease was defined by ultrasonographic examination.
      Subjects were divided into 4 groups according to the baseline quartiles of
      fasting insulin and dichotomized fasting insulin levels at baseline and after 5
      years: low-low, low-high, high-low, high-high. RESULTS: after 5 years, 644
      subjects (13%) developed nonalcoholic fatty liver disease. The odds ratio (OR)
      for development of nonalcoholic fatty liver disease increased as the quartiles of
      the baseline fasting insulin levels increased from the first to the fourth
      quartile (1.00 vs. 0.99, 1.44, 1.65, respectively). The OR for nonalcoholic fatty
      liver disease was 2.5-fold higher in the high-high group and 1.6-fold higher in
      the low-high group compared with that of the low-low group. The OR for
      nonalcoholic fatty liver disease increased as the quartile of changes in fasting
      insulin level over the 5-year period increased. CONCLUSION: high baseline and
      continuously increasing fasting insulin levels were the independent determinants
      for future development of nonalcoholic fatty liver disease during a 5-year follow
      up in nondiabetic healthy adults.

PMID- 21187190
TI  - Internal medicine residency training on topics in ambulatory care: a status
      report.

PMID- 21187188
TI  - Mortality associated with low serum sodium concentration in maintenance
      hemodialysis.
AB  - BACKGROUND: low serum sodium concentrations are associated with an increased risk
      of death in the general population, but causality is uncertain due to confounding
      from clinical conditions such as congestive heart failure and cirrhosis, in which
      hyponatremia results from elevated levels of arginine vasopressin. METHODS: to
      examine the association between predialysis serum sodium concentration and
      mortality in patients undergoing hemodialysis for end-stage renal disease, a
      condition in which arginine vasopressin does not affect water excretion and
      osmoregulation, we studied 1549 oligoanuric participants in the HEMO study, a
      randomized controlled trial of hemodialysis patients examining the effect of
      hemodialysis dose and flux. We used proportional hazards models to compare the
      risk of death according to predialysis serum sodium concentration. RESULTS:
      considered as a continuous variable, each 4-mEq/L increment in baseline
      predialysis serum sodium concentration was associated with a hazard ratio for all
      cause mortality of 0.84 (95% confidence interval (CI), 0.78-0.90). Multivariable
      adjustment for demographic, clinical, laboratory, and dialysis-specific
      covariates, including ultrafiltration volume, did not appreciably change the
      results (hazard ratio for all-cause mortality of 0.89; 95% CI, 0.82-0.96). the
      results also were consistent in time-updated analyses using repeated measures of
      serum sodium and other relevant covariates. CONCLUSION: Lower predialysis serum
      sodium concentration is associated with an increased risk of death. Considering
      the unique physiology in the dialysis population, these findings raise the
      possibility that hyponatremia itself may be a causal determinant of mortality in
      the broader population.

PMID- 21187189
TI  - Effects of alpha-lipoic Acid on body weight in obese subjects.
AB  - PURPOSE: alpha-lipoic acid is an essential cofactor for mitochondrial respiratory
      enzymes that improves mitochondrial function. We previously reported that alpha
      lipoic acid markedly reduced body weight gain in rodents. The purpose of this
      study was to determine whether alpha-lipoic acid reduces body weight in obese
      human subjects. METHODS: in this randomized, double-blind, placebo-controlled, 20
      week trial, 360 obese individuals (body mass index [BMI] >= 30 kg/m(2) or BMI 27
      30 kg/m(2) plus hypertension, diabetes mellitus, or hypercholesterolemia) were
      randomized to alpha-lipoic acid 1200 or 1800 mg/d or placebo. The primary end
      point was body weight change from baseline to end point. RESULTS: the 1800 mg
      alpha-lipoic acid group lost significantly more weight than the placebo group
      (2.1%; 95% confidence interval, 1.4-2.8; P<.05). Urticaria and itching sensation
      were the most common adverse events in the alpha-lipoic acid groups, but these
      were generally mild and transient. CONCLUSION: alpha-lipoic acid 1800 mg/d led to
      a modest weight loss in obese subjects. Alpha-lipoic acid may be considered as
      adjunctive therapy for obesity.

PMID- 21187191
TI  - Discussion: 'Testing for biomarkers after ASC-US Pap smears' by Lin et al.
AB  - In the roundtable that follows, clinicians discuss a study published in this
      issue of the Journal in light of its methodology, relevance to practice, and
      implications for future research. Article discussed: Lin CJ, Lai H-C, Wang KH, et
      al. Testing for methylated PCDH10 or WT1 is superior to the HPV test in detecting
      severe neoplasms (CIN3 or greater) in the triage of ASC-US smear results. Am J
      Obstet Gynecol 2011;204:21.e1-7.

PMID- 21187192
TI  - Patient safety series.

PMID- 21187193
TI  - Timing of delivery in fetal growth restriction and childhood development: some
      uncertainties remain.

PMID- 21187195
TI  - Overview of progress in patient safety.
AB  - In the 11 years since the Institute of Medicine reported ubiquitous problems with
      the quality and safety of patient care in the United States, efforts been made to
      improve health care. Obstetrics and gynecology has made some improvements;
      however, similar to other areas of health care, progress has been slow. The major
      deterrents are complexities in our health care system and culture and an immature
      science of safety and quality that makes measurement and evaluation of progress
      difficult. This article describes the efforts that have been made in obstetrics
      and gynecology to identify causes or factors that contribute to adverse outcomes,
      to develop measures of quality and safety, and to make improvements. It also
      offers a framework to help organize patient safety research and improvement.
      Finally, this article offers ways the American Congress of Obstetricians and
      Gynecologists can organize and support future work.

PMID- 21187196
TI  - Risks of stress urinary incontinence and pelvic organ prolapse surgery in
      relation to mode of childbirth.
AB  - OBJECTIVE: To estimate the risk for stress urinary incontinence and pelvic organ
      prolapse surgery related to vaginal birth or cesarean delivery. STUDY DESIGN: A
      cohort study of all women having their first and all subsequent deliveries by
      cesarean (n = 33,167), and an age-matched sample of women only having vaginal
      deliveries (n = 63,229) between 1973 and 1983. Hazard ratios were calculated
      using Cox regression models with 95% confidence intervals. RESULTS: Women only
      having vaginal deliveries had increased overall risks of incontinence (hazard
      ratio, 2.9; 95% confidence interval, 2.4-3.6) and prolapse surgery (hazard ratio,
      9.2; 95% confidence interval, 7.0-12.1) compared with women only having cesarean
      deliveries. CONCLUSION: Having only vaginal childbirths was associated with a
      significantly increased risk of stress urinary incontinence and pelvic organ
      prolapse surgery later in life compared with only having cesarean deliveries.

PMID- 21187197
TI  - Can hysterosalpingo-contrast sonography replace hysterosalpingography in
      confirming tubal blockage after hysteroscopic sterilization and in the evaluation
      of the uterus and tubes in infertile patients?
AB  - OBJECTIVE: The objective of the study was to assess the accuracy of
      hysterosalpingo-contrast sonography (HyCoSy) in establishing tubal patency or
      blockage and evaluating the uterine cavity by comparing it with hysteroscopy
      laparoscopy (HLC) or hysterosalpingography (HSG). STUDY DESIGN: This study was a
      chart review evaluating infertility patients and patients who had undergone
      hysteroscopic sterilization who underwent both HyCoSy and HLC or HyCoSy and HSG
      at private offices associated with university hospitals. Sensitivity,
      specificity, positive predictive value, and negative predictive value of HyCoSy
      were calculated. RESULTS: HyCoSy compared with HLC had a sensitivity of 97% and
      specificity of 82%, and HyCoSy compared with HSG was 100% concordant. Uterine
      cavities evaluated by sonohysterography and hysteroscopy were 100% concordant.
      CONCLUSION: HyCoSy is accurate in determining tubal patency and evaluating the
      uterine cavity, suggesting it could supplant HSG not only as the first-line
      diagnostic test in an infertility workup but also in confirming tubal blockage
      after hysteroscopic sterilization.

PMID- 21187200
TI  - Stimulation of acupoint ST-34 acutely improves gait performance in geriatric
      patients during rehabilitation: A randomized controlled trial.
AB  - OBJECTIVE: To determine whether a specific regimen of acupoint stimulation
      improved gait performance in geriatric patients. DESIGN: Multiple-blinded,
      randomized, controlled intervention trial. SETTING: Geriatric ward
      rehabilitation. PARTICIPANTS: 60 geriatric patients during rehabilitation.
      INTERVENTIONS: Both groups received a 1-time acupoint stimulation according to
      randomization. Stimulation of a verum acupoint (verum treatment) according to
      principles of traditional Chinese medicine was compared with a technically
      identical needle application on a nonacupoint (control treatment) in the control
      group. MAIN OUTCOME MEASURES: Descriptive parameters were documented by valid,
      established tests. Gait performance was objectively measured by an electronic
      walkway before needling and after needling. RESULTS: All gait parameters showed
      statistically significant improvement after verum treatment compared with control
      treatment (velocity, cadence, stride length, cycle time, step time, single
      support, double support: P values all <.05) except for the base of support
      (P=.163). Effect sizes achieved by 1-time stimulation of an acupoint were low and
      ranged from .08 to .24. No severe adverse clinical events related to the
      intervention occurred. CONCLUSIONS: Study results showed that a 1-time
      administration of a specific acupoint stimulation regimen statistically
      significantly improved gait performance during geriatric ward rehabilitation. If
      sustainability of effects can be documented, acupuncture may prove to be an
      inexpensive intervention that may mildly improve motor performance in frail
      geriatric patients.

PMID- 21187199
TI  - Median nerve conduction study through the carpal tunnel using segmental nerve
      length measured by ultrasonographic and conventional tape methods.
AB  - OBJECTIVE: (1) To determine whether a 5-cm segment includes the entire anatomic
      carpal tunnel in live subjects, and to compare surface, ultrasonographic, and
      direct measures of the median nerve length in human cadavers. (2) To investigate
      the actual difference of sensory conduction velocities between the conventional
      tape method and the ultrasonographic method. DESIGN: Cross-sectional study.
      SETTING: University rehabilitation hospital. PARTICIPANTS: Healthy volunteers
      (N=40; 20 men, 20 women). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Onset latencies at the palm and wrist, nerve conduction velocity (NCV) in nerve
      conduction study (NCS), median nerve length measured by ultrasound and tape
      method. RESULTS: A real-time ultrasonographic study revealed that a 5-cm segment
      included the entire carpal tunnel. In the cadaveric study, the median nerve
      length measured by ultrasound was closer to the actual nerve length than the
      conventional surface length. The median nerve length in the wrist-to-palm segment
      measured by ultrasound was shorter than the surface distance. The sensory NCV
      using the nerve length measured by ultrasound was slower than that using the
      surface distance (P<.05). CONCLUSIONS: The 5-cm segment test included the entire
      carpal tunnel and might be advantageous in the diagnosis of carpal tunnel
      syndrome (CTS), especially for early lesions. We expect that ultrasonographic
      measurement of nerve length might raise the sensitivity of NCSs for the diagnosis
      of CTS.

PMID- 21187201
TI  - Effects of sensory cueing on voluntary arm use for patients with chronic stroke:
      a preliminary study.
AB  - OBJECTIVE: To investigate the effect of a 2-week program of sensory cueing in
      which vibration induces the use of the paretic upper extremity in participants
      with chronic stroke in the community. DESIGN: A single-group longitudinal study.
      SETTING: Self-help organizations. PARTICIPANTS: A convenience sample of 16
      community residents (N=16) with chronic unilateral stroke and mild to moderate
      upper-extremity impairment stratified by the severity of their paretic arm
      function, measured by using the Functional Test for the Hemiplegic Upper
      Extremity (FTHUE). INTERVENTIONS: Participants engaged in repetitive upper
      extremity task practice for 2 weeks while wearing an ambulatory sensory cueing
      device on their affected hand for 3 hours a day. MAIN OUTCOME MEASURES:
      Evaluations were conducted on the 3 occasions of pretest (1 day before training),
      posttest (immediately after training), and follow-up test (2 weeks after
      training) by using the following behavioral measures of paretic upper-extremity
      performance: the Action Research Arm Test (ARAT), the Box and Block Test, the
      Fugl-Meyer Assessment (FMA), the FTHUE, power and pinch grips, the Motor Activity
      Log assessment of arm use, and kinematic data obtained from the device. RESULTS:
      Significant differences were found in ARAT and FMA scores among the pretest,
      posttest, and follow-up evaluations. The lower functioning group achieved a more
      significant increase in overall upper-extremity score than in the hand score for
      the FMA. CONCLUSION: A combination of sensory cueing and movement-based
      strategies is useful and feasible in improving paretic upper-extremity
      performance in participants with chronic stroke; however, additional studies with
      a larger sample size and longer treatment period in a randomized controlled trial
      would be beneficial.

PMID- 21187202
TI  - Effects of 12 weeks of supported treadmill training on functional ability and
      quality of life in progressive multiple sclerosis: a pilot study.
AB  - OBJECTIVE: To examine the effects of body-weight supported treadmill training
      (BWSTT) on functional ability and quality of life in patients with progressive
      multiple sclerosis (MS) of high disability. DESIGN: Before-after trial. SETTING:
      Exercise rehabilitation research center. PARTICIPANTS: Patients with progressive
      MS (N=6; 5 primary progressive, 1 secondary progressive) with high disability
      (mean+/-SD expanded disability status scale, [EDSS]=6.9+/-1.07). All participants
      completed the trial. INTERVENTIONS: Subjects completed 36 sessions of BWSTT (30
      min sessions, 3*wk) over 12 weeks. MAIN OUTCOME MEASURES: Outcome measures
      included functional ability assessed by EDSS and Multiple Sclerosis Functional
      Composite (MSFC). Quality of life and fatigue were assessed by the MS Quality of
      Life-54 (MSQoL-54) and the Modified Fatigue Impact Scale (MFIS), respectively.
      All tests were administered at baseline and after 12 weeks of training. RESULTS:
      All participants progressively improved training intensity; treadmill walking
      speed increased (34%; P<.001), and percent body weight support was reduced (42%;
      P<.001). A significant improvement in both physical (P=.02) and mental (P=.01)
      subscales of the MSQoL-54 was found. Fatigue was nonsignificantly reduced by 31%
      (P=.22); however, a large effect size (ES) was noted (ES=-.93). Functional
      ability remained stable with nonsignificant improvements in MSFC (P=.35; ES=.23)
      and EDSS (P=.36; ES=-.08) scores. CONCLUSIONS: Twelve weeks of BWSTT produces
      beneficial effects on quality of life and potentially reduces fatigue in patients
      with primary progressive MS of high disability level. Larger trials will be
      required to confirm these findings and to evaluate further the effects of BWSTT
      in progressive MS.

PMID- 21187203
TI  - Effects of combined aerobic and resistance exercise training in adults with and
      without Down syndrome.
AB  - OBJECTIVE: To determine whether adults with Down syndrome (DS) could improve
      their submaximal and peak exercise capacity, as for adults without disabilities,
      after 12 weeks of combined (aerobic and resistance) exercise training. DESIGN:
      Prospective study comparing the effects of a 12-week combined exercise program on
      submaximal and peak exercise capacity of adults with and without DS. SETTING:
      University facilities. PARTICIPANTS: Participants with DS (n=13; mean +/- SD age,
      36.5+/-5.5y) and participants without disabilities (n=12; mean age, 38.7+/-8.3y).
      INTERVENTIONS: Combined exercise training for 12 weeks. Endurance training was
      performed 3 days a week for 30 minutes at 65% to 85% of peak oxygen consumption
      (Vo2peak). Resistance training was prescribed for 2 days a week and consisted of
      2 rotations in a circuit of 9 exercises at 12-repetition maximum. MAIN OUTCOME
      MEASURES: Submaximal and maximal graded exercise tests with metabolic and heart
      rate measurements. Walking economy and Vo2peak were considered the main outcomes.
      RESULTS: Participants with DS and those without disabilities showed similar
      values for body mass index and relative fat mass at pre- and posttraining
      periods. Walking economy and Vo2peak overall were lower in participants with DS
      than participants without disabilities (P<.05). Training improved walking economy
      and Vo2peak in participants with DS and those without disabilities (P<.05);
      additionally, the magnitude of changes induced by training was similar between
      groups. CONCLUSIONS: Overall, a 12-week combined exercise regimen induced gains
      of similar magnitude between adults with and without DS for submaximal and peak
      exercise capacity.

PMID- 21187204
TI  - Reasons for hospital admissions among youth and young adults with cerebral palsy.
AB  - OBJECTIVE: To identify the most common reasons for acute care hospital admissions
      among youth (age range, 13-17.9y) and young adults (age range, 23-32.9y) with
      cerebral palsy (CP). DESIGN: We completed a secondary analysis of data from the
      Canadian Institute for Health Information (CIHI) to determine the most frequently
      observed reasons for admissions and the associated lengths of stay (LOS).
      SETTING: Participants were identified from 6 children's treatment centers in
      Ontario, Canada. PARTICIPANTS: Health records data from youth with CP (n=587) and
      young adults with CP (n=477) contributed to this study. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: The most common reasons for hospital
      admission, relative frequencies of admissions for each reason, and mean LOS were
      reported. RESULTS: The analysis of CIHI records identified epilepsy and pneumonia
      as the top 2 reasons for admissions in both age groups. Both age groups were
      commonly admitted because of infections other than pneumonia and urinary tract
      infections (UTIs), gastrointestinal (GI) problems such as malabsorption, and
      mental illness. The reasons that were unique to youth included orthopedic and
      joint-related issues, other respiratory problems, and scoliosis. In young adults,
      mental illness was the third most common reason for admission, followed by lower
      GI or constipation problems, malnutrition or dehydration, upper GI problems,
      fractures, and UTIs. CONCLUSIONS: This article provides important clinical
      information that can be used in the training of physicians and health care
      providers, and to guide future planning of ambulatory care services to support
      the clinical management of persons with CP over their lifespan.

PMID- 21187205
TI  - Clinimetric properties of the de Morton Mobility Index in healthy, community
      dwelling older adults.
AB  - OBJECTIVE: To investigate the clinimetric properties of the de Morton Mobility
      Index (DEMMI) in healthy, community-dwelling older adults. DESIGN: Cohort study.
      SETTING: Retirement village and Returned and Services League (RSL) club in
      Melbourne, Australia. PARTICIPANTS: All participants were 65 years or older,
      healthy, and living within the community. The validation study included
      participants recruited from a retirement village (n=61), and the reliability
      studies included participants recruited from an RSL club and a subset of
      participants from the retirement village. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Mobility was assessed using the DEMMI. The percentage of
      participants who scored the highest and lowest possible score on the DEMMI was
      calculated to determine whether a floor or ceiling effect occurred. The minimal
      clinically important difference (MCID) was estimated using a distribution-based
      method. Reliability was assessed independently and concurrently using the minimal
      detectable change at 90% confidence (MDC90). RESULTS: Evidence of convergent and
      discriminant validity was obtained for the DEMMI by examining correlations with
      measures of related constructs, the Lower Extremity Functional Scale (r=.69) and
      Quality of Life Scale scores (r=.28), respectively. Participants who ambulated
      without a gait aid (82.62+/-10.63) had significantly higher (P<.0) DEMMI scores
      than those who ambulated with an aid (64.1+/-12.40), providing evidence of known
      groups validity. No floor or ceiling effect was identified. The MCID was 7
      points. The MDC90 was 13 (95% CI, 8.76-17.05) points on the 100-point scale.
      CONCLUSION: DEMMI scores in healthy, community-dwelling older adults are both
      valid and reliable.

PMID- 21187206
TI  - Osteoporosis in persons with spinal cord injury: the need for a targeted
      therapeutic education.
AB  - OBJECTIVES: To identify circumstances surrounding the onset of fracture and
      common risk factors in persons with spinal cord injury (SCI) and to suggest an
      alternative or complement to the pharmacologic approach by evaluating the need
      for a prospective study based on the impact of a targeted therapeutic education
      on risk management of fractures in this population. DESIGN: Retrospective study.
      SETTING: Hospital and Rehabilitation Center Setting. PARTICIPANTS: Women (n=7)
      and men (n=25; N=32; with >=1 fracture after the initial SCI that occurred at
      home or in a hospital setting; mean +/- SD age, 53+/-12y at the time of clinical
      review) with bone mineral density (BMD) measurements. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Demographics, main circumstances of onset, and
      complications of fractures, as well as transversal bone mineral density
      evaluation. RESULTS: Nine patients had more than 1 fracture and 23 patients had
      only 1 fracture (total, 43 fractures; mean age at onset of fracture, 49+/-12y;
      median time since injury, 13.9y; mean delay in diagnosis, 6.5+/-15d). Fractures
      occurred mostly in the lower limbs. The circumstances of onset of these fractures
      were different and very stereotyped. In 3 cases, no trauma was reported. The most
      frequent mechanisms identified were forced maneuvers by the patient or a third
      party and falls. In 10 cases, the fracture occurred during a wheelchair transfer
      with forced maneuver or a fall from the wheelchair. Twenty-five patients were
      confined to bed after the fracture (mean duration of bed confinement, 18+/-28d;
      range, 0-120d). Postfracture follow-up showed that for 43 cases of fractures, 19
      had at least 1 orthopedic complication, 15 had local complications, and 23 had
      general complications. Patients (23 of 32) benefited from dual-energy X-ray
      absorptiometry to assess BMD a few months or years after the fracture (mean
      femoral neck BMD, 0.574+/-0.197g/cm2; mean femoral neck T score, -3.8+/-1.5).
      CONCLUSION: With this retrospective analysis of common risk factors and
      circumstances of onset of secondary fractures, there is a clear future for a
      prospective study to evaluate the impact of targeted therapeutic education on
      risk factors for secondary fractures in patients with SCI.

PMID- 21187207
TI  - Foot and ankle strength, range of motion, posture, and deformity are associated
      with balance and functional ability in older adults.
AB  - OBJECTIVE: To determine the extent to which measures of foot and ankle strength,
      range of motion, posture, and deformity are associated with performance in a
      battery of balance and functional ability tests in older adults. DESIGN: Cross
      sectional study of people over 65 years. SETTING: Community. PARTICIPANTS:
      Participants (N=305; age range, 65-93y) recruited for a randomized trial
      investigating the efficacy of a podiatry intervention to prevent falls.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Clinical measures of foot
      and ankle strength (using hand-held dynamometry), range of motion, posture, and
      deformity, and a battery of balance tests (postural sway, maximum balance range,
      lateral stability, coordinated stability) and functional ability tests (alternate
      step test, sit-to-stand, timed 6-m walk). RESULTS: Most (67/88) of the
      correlations between the foot and ankle tests and performance on the balance and
      functional tests were statistically significant. Hierarchic linear regression
      analysis identified hallux plantar flexion strength and ankle inversion-eversion
      range of motion to be the most consistent significant and independent predictors
      of balance and functional test performance, explaining up to 25% of the variance
      in the test scores. CONCLUSIONS: Foot and ankle characteristics, particularly
      plantar flexor strength of the hallux and ankle inversion-eversion range of
      motion, are important determinants of balance and functional ability in older
      people. Further research is required to establish whether intervention programs
      that include strengthening and stretching exercises for the foot and ankle may
      achieve improvements in balance and functional ability and reduce the risk of
      falls in older people.

PMID- 21187208
TI  - Normalizing hip muscle strength: establishing body-size-independent measurements.
AB  - OBJECTIVE: To investigate the effectiveness of computing body-size-independent
      hip strength measures using muscle-specific allometric scaling and ratio standard
      normalization methods. DESIGN: Cross-sectional study. SETTING: University
      laboratory. PARTICIPANTS: A convenience sample of healthy participants (N=113; 42
      men, 71 women). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Anthropometric measurements of the leg and thigh were obtained, and maximal hip
      strength was tested (medial and lateral rotation, abduction, adduction, flexion,
      extension). Strength was measured isometrically as force (kg) and then converted
      to torque (Nm). RESULTS: The allometric scaling analysis resulted in exponents
      for normalizing body mass (BM) in each muscle group assessed. In addition, a 6
      muscle average exponent was also computed (bavg) for force (men, .554; women,
      .335) and torque (men, .792; women, .482). The nonsignificant results of the
      linear regression analysis revealed that normalizing hip strength to BM(bavg)
      (hip strength/BM(bavg)) effectively removed the influence of BM on force and
      torque. However, sex should be factored into analyses of allometric scaling
      because men have higher b-values than women for both force and torque. The linear
      regression analyses also demonstrated that force normalized to BM (P=.162-.895)
      and torque normalized to BM * Height (P=.146-.889) were body-size-independent
      measures. Force normalized to BM0.67 (P=.001-.191) and body mass index (BMI)
      (P=<.001-.066), and torque normalized to BM (P=.004-.415) and BMI (P<.001) were
      significantly related to BM and therefore were not body-size independent.
      CONCLUSIONS: Normalizing force and torque to BM(bavg) is the most effective
      method of removing body-size dependence and allowing comparisons of persons with
      differing body sizes.

PMID- 21187209
TI  - Handgrip strength test as a complementary tool in the assessment of fibromyalgia
      severity in women.
AB  - OBJECTIVES: To determine the ability of handgrip strength test to discriminate
      between presence and absence of fibromyalgia (FM) and FM severity in women.
      DESIGN: A case-control study. SETTING: Granada, south Spain. PARTICIPANTS: Women
      with FM (mean age +/- SD, n=81; 50.0+/-7y) and healthy women (mean age +/- SD,
      n=44; 47.7+/-6y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Handgrip
      strength was measured in both hands (average score was used in the analyses) by a
      maximal isometric test using a hand dynamometer. Patients were classed as having
      moderate FM if the score in the Fibromyalgia Impact Questionnaire (FIQ) was less
      than 70 and as having severe FM if the FIQ was 70 or greater. RESULTS: Handgrip
      strength levels were lower in patients with FM than healthy women (19.3 vs
      27.9kg; P<.001) and in women with severe FM (FIQ>=70) compared with those with
      moderate FM (FIQ<70) (16.9 vs 20.2kg; P=.02). Receiver operating characteristic
      curve analyses revealed that the handgrip strength threshold that best
      discriminated between the presence and absence of FM was 23.1kg (area under the
      curve [AUC]=.88; 95% confidence interval [CI], 0.82-0.94; P<.001), whereas the
      handgrip strength threshold that best discriminate between severe and moderate FM
      was 16.9kg (AUC=.67; 95% CI, 0.53-0.80; P<.05). Logistic regression analysis
      showed that handgrip strength 23.1kg or less was associated with 33.8 times
      higher odds (95% CI, 9.4-121.5) for having FM after adjustment for age. In the FM
      group, handgrip strength 16.9kg or less was associated with 5.3 times higher odds
      (95% CI, 1.9-14.5) for having severe FM. CONCLUSIONS: Handgrip strength is
      reduced in women with FM as well as those with severe FM from their peers with
      moderate FM. Identification of women who fail to meet the suggested standards can
      be a helpful and informative tool for clinician.

PMID- 21187211
TI  - Predictors of stenosing tenosynovitis in the hand and hand-related activity
      limitations in patients with rheumatoid arthritis.
AB  - OBJECTIVES: To identify early predictors of stenosing tenosynovitis in the hand
      and hand-related activity limitations in patients with rheumatoid arthritis (RA).
      DESIGN: A longitudinal study of an inception cohort. SETTING: A large outpatient
      clinic. PARTICIPANTS: Consecutive patients who attended the Early Arthritis
      Clinic for at least 2 years and fulfilled the American College of Rheumatology
      criteria for RA at baseline and/or at the 1-year follow-up were invited to
      participate until 200 patients were included. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Stenosing tenosynovitis, assessed by means of a standardized
      physical examination. Hand-related activity limitations, assessed with the
      Disabilities of Arm, Shoulder and Hand questionnaire (DASH). A DASH score above
      the upper limit of the 95% range of the normative score was defined as abnormal.
      Prognostic factors: demographic and disease activity-related variables,
      radiographic damage, the Health Assessment Questionnaire (HAQ) total score and
      category scores at the 2-year follow-up. RESULTS: The mean age +/- SD of the
      patients was 59.7+/-10.7 years (75% female). The mean time +/- SD between the 2
      year follow-up and the assessment of the dependent variables was 3.9+/-2.7 years.
      Stenosing tenosynovitis was present in 33%. The median (interquartile range) DASH
      score was 26.7 (10.8-42.5); 30% were abnormal. Stenosing tenosynovitis was
      predicted by the HAQ subscale regarding the use of hands (HAQ-hand) at the 2-year
      follow-up (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.2-4.2). Hand
      related activity limitations were predicted by the Disease Activity Score in 28
      joints (OR, 1.8; 95% CI, 1.3-2.4) and HAQ-hand (OR, 2.4; 95% CI, 1.3-5.8) at the
      2-year follow-up. CONCLUSIONS: Stenosing tenosynovitis in patients with RA was
      predicted by HAQ-hand at the 2-year follow-up, and hand-related activity
      limitations were predicted by disease activity and HAQ-hand at the 2-year follow
      up.

PMID- 21187210
TI  - Pain perception after isometric exercise in women with fibromyalgia.
AB  - OBJECTIVE: The purpose of this study was to identify exercise protocols
      incorporating isometric contractions that provide pain relief in women with
      fibromyalgia. DESIGN: A before-after trial. SETTING: A physical therapy
      department in an academic setting. PARTICIPANTS: Fifteen women (mean +/- SD, 52+/
      11y) with fibromyalgia. INTERVENTIONS: Subjects completed 4 sessions: 1
      familiarization and 3 experimental. The following randomized experimental
      sessions involved the performance of isometric contractions with the elbow flexor
      muscles that varied in intensity and duration: (1) 3 maximal voluntary
      contractions (MVCs), (2) 25% MVC held to task failure, and (3) 25% MVC held for 2
      minutes. MAIN OUTCOME MEASURES: Experimental pain (pain threshold and pain
      rating), Fibromyalgia Impact Questionnaire, and fibromyalgia pain intensity
      (visual analog scale). RESULTS: After all 3 isometric contractions, there was
      considerable variability between subjects in the pain response. Based on the
      changes in experimental pain, subjects were divided into 3 groups (increase,
      decrease, no change in pain). Multiple regression analysis revealed that age,
      baseline experimental pain, and change in fibromyalgia pain intensity were
      significant predictors of the experimental pain response after the isometric
      contractions. CONCLUSIONS: We identified subgroups of women with fibromyalgia
      based on how they perceived pain after isometric contractions. The greatest pain
      relief for women with fibromyalgia occurred at a younger age and in women with
      the greatest experimental pain before exercise. Additionally, we established a
      link between experimental and clinical pain relief after the performance of
      isometric contractions.

PMID- 21187212
TI  - Further validation of the Balance Outcome Measure for Elder Rehabilitation.
AB  - OBJECTIVE: To determine the concurrent validity of the Balance Outcome Measure
      for Elder Rehabilitation (BOOMER) with both the Berg Balance Scale (BBS) and gait
      speed. DESIGN: Prospective cohort study. SETTING: Two geriatric rehabilitation
      units. PARTICIPANTS: Elderly adults (N=134) admitted to inpatient rehabilitation.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The BOOMER consists of
      timed static stance feet together eyes closed, Functional Reach, step test, and
      the Timed Up and Go test. Validity was determined using the Spearman correlation
      coefficient, comparing the BOOMER with the BBS and gait speed on admission and
      discharge. Responsiveness of the BOOMER was compared with the BBS and gait speed
      for the change scores between admission and discharge using the Spearman
      correlation coefficient. RESULTS: The BOOMER demonstrated high to very high
      correlation with the BBS at admission (rho=.91; P<.01) and discharge (rho=.89;
      P<.01), and with gait speed at admission (rho=.67; P<.01) and discharge (rho=.68;
      P<.01). Change scores between admission and discharge for the BOOMER and BBS
      displayed moderate correlation (rho=.55; P<.01), while those between the BOOMER
      and gait speed displayed only fair correlation (rho=.33 P<.01). CONCLUSION: The
      BOOMER appears to be a valid measure of the standing balance construct because it
      demonstrated high correlation with another measure of balance, and moderate
      correlation with a measure of a related construct (gait speed). The BOOMER may be
      a worthwhile alternative for more complex multi-item balance measures.

PMID- 21187213
TI  - Driving with a chronic whiplash-associated disorder: a review of patients'
      perspectives.
AB  - OBJECTIVE: To document troublesome driving tasks and any changes in driving
      behavior reported by people with chronic whiplash-associated disorders (WADs).
      DESIGN: Descriptive study; semistructured interview. SETTING: Tertiary
      institution. PARTICIPANTS: Patients (N=33) with chronic WAD. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Neck Disability Index (NDI), visual analog
      scale for neck pain at rest and while driving, exposure section of the Driving
      Habit Questionnaire, self-rating perceived current driving ability,
      semistructured interview about presenting symptoms, troublesome driving tasks,
      and perceived changes in driving behavior after a whiplash injury. RESULTS:
      Subjects (24 of 33; 73%) reported a decrease in driving ability, rating an
      average of 6.7+/-2.2 on an 11-point scale (0, unable to drive; 10, driving at
      preinjury level). These subjects scored higher on the NDI (41.8%+/-18.4%),
      experienced greater neck pain at rest (4.3+/-2.1/10) and while driving (5.7+/
      2.1/10), and reported decreased concentration more frequently than those who
      rated their driving ability at a preinjury level (ie, 10). The most frequently
      nominated troublesome driving tasks were checking blind spots, prolonged driving,
      and reversing/reverse parking, and the most frequently cited changes in driving
      behavior included more use of trunk rotation (75%), altered steering wheel grip
      (63%), more anxious/nervous while driving (54%), and more cautious driving (50%).
      CONCLUSIONS: The chronic whiplash population appears to have unique troublesome
      driving tasks (eg, prolonged driving, checking blind spots) that are not readily
      detected in currently available driving ability/difficulty scales, suggesting
      that a new scale may be required for this population.

PMID- 21187214
TI  - Sex disparities in level of amputation.
AB  - OBJECTIVE: To determine whether there is a sex-related disparity in the
      management of lower-extremity ischemia by evaluating the relationship between sex
      and level of nontraumatic amputation. DESIGN: This is a retrospective secondary
      analysis of community hospital data from the Healthcare Cost and Utilization
      Project, Nationwide Inpatient Sample for 2007. Level of amputation was determined
      from International Classification of Diseases-9th Revision-Clinical Modifications
      procedure and coded as either transfemoral or transtibial. The main predictor was
      sex; covariates including age, race, income, insurance status, and presence of
      vascular disease were incorporated as control variables in regression analysis.
      SETTING: Nonfederal, short-term U.S. community hospitals. PARTICIPANTS: Persons
      discharged from hospitals with a nontraumatic transtibial or transfemoral
      amputation (N=11,114). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Level of limb loss. RESULTS: A significant association was found between female
      sex and transfemoral amputation in both the bivariable (chi2=187.0; P<.000) and
      multivariable analysis (odds ratio [OR]=1.4; 95% confidence interval [CI]=1.3
      1.5). Other covariates significant for influencing level of amputation during
      multivariable analysis include age, with highest age greater than 78 years at
      highest risk (OR=3.0; 95% CI, 2.6-3.5); 0-25% quartile of income or annual income
      less than $36,000 (OR=1.3; 95% CI, 1.1-1.5); Medicare insurance (OR=1.4; 95% CI,
      1.1-1.6); Medicaid insurance (OR=1.3; 95% CI, 1.3-1.6); and cerebrovascular
      disease (OR=2.0; 95% CI, 1.7-2.4). CONCLUSIONS: Female sex is significantly
      associated with transfemoral amputation compared with male sex. Transfemoral
      amputation has significant consequences, and further evaluation of preventative
      care and screening for women with vascular disease should be considered.

PMID- 21187215
TI  - Metastatic paraplegia and vital prognosis: perspectives and limitations for
      rehabilitation care. Part 1.
AB  - OBJECTIVE: To evaluate the vital prognosis of patients with metastatic epidural
      spinal cord compression (MESCC) to determine the relevance and duration of
      physical medicine and rehabilitation (PM&R) admission. DATA SOURCES: Publications
      from 1980 to January 2010 selected from 3 databases. STUDY SELECTION:
      Publications reporting data correlated with survival and prognosis factors,
      highlighting publications with level A scientific evidence (prospective
      randomized controlled studies with significant casuistry and relevant judgment
      criteria). The work focused on patients with MESCC below T1. DATA EXTRACTION:
      Standardized reading grid. DATA SYNTHESIS: Thirty-eight studies met the inclusion
      criteria. Most were retrospective. For survival rate at 1 year, they reported
      data ranging from 12% to 58%. The 12-month and median survival rates were the
      data reported most often in the articles. The median survival rate ranged from
      2.4 to 30 months, and 12-month survival rates ranged from 12% to 58%. Of
      publications that chose this parameter, 95% reported 12-month survival rates less
      than 55.2% (95th percentile) regardless of patients' functional status and
      associated risk factors (eg, location of primary cancer, metastases spreading,
      pretreatment ambulatory status). CONCLUSIONS: Despite major progress in cancer
      care, patients with MESCC still have a limited vital prognosis. The relevance and
      duration of PM&R care must be evaluated against the patient's functional need for
      rehabilitation while making time for family. The hypothesis of a 1-month stay
      extended only once appears reasonable for patients to adapt to their new
      functional status without taking precious time away from their loved ones.

PMID- 21187216
TI  - Metastatic paraplegia and functional outcomes: perspectives and limitations for
      rehabilitation care. Part 2.
AB  - OBJECTIVE: To identify functional outcomes that could justify the need for a
      rehabilitation care program for patients with metastatic epidural spinal cord
      compression (MESCC) and paraplegia. DATA SOURCES: Publications from 1950 to
      January 2010 selected from 3 databases. STUDY SELECTION: Original articles
      dealing with outcome data for functional status, pain, and bladder dysfunction.
      DATA EXTRACTION: Standardized reading grid. DATA SYNTHESIS: The data are
      dominated by retrospective studies for even functional-related data, and studies
      from rehabilitation teams are rare. They report a functional evolution similar to
      a population with traumatic spinal cord injury for the first 3 months. Patients
      who were ambulatory before treatment retained their ability to walk, and patients
      who were nonambulatory before treatment could regain gait abilities. Data also
      showed a positive impact on pain and bladder and/or bowel dysfunction.
      CONCLUSIONS: By restricting physical medicine and rehabilitation therapeutic care
      to a short time (1-2mo), the progression margin is possible in the short term and
      implies a voluntary and active therapeutic care approach for patients with
      paraplegia after MESCC on the basis of a codified and standardized program with
      clinical indicators, as well as patients' comfort indicators.

PMID- 21187218
TI  - A report on disability and rehabilitation medicine in Pakistan: past, present,
      and future directions.
AB  - Disability is a stigma in Pakistan, and cultural norms are a hindrance to the
      integration of the disabled into the community. Additional barriers to addressing
      the needs of the disabled include the lack of reliable disability epidemiologic
      data, inadequate funding and poor health care infrastructure, and workforce
      shortages. The aim of this report is to present an overview of Physical Medicine
      and Rehabilitation (PM&R) in Pakistan, covering its origins, current status, and
      future directions. An electronic literature search (1950-2009) was conducted
      using the Medline, ScienceDirect, Springer Link, CINAHL, and Google Scholar
      databases. The key words used were "disability," "persons with disability"
      (PWDs), "rehabilitation," "Pakistan," "developing countries," "stroke," "spinal
      cord injury," "causes," "attitudes," "physiotherapy," "occupational therapy," and
      "speech therapy." Only publications in English involving physical disability were
      selected. Statistical data were obtained from the Federal Bureau of Statistics.
      Interviews with pioneers of rehabilitation medicine in Pakistan, PWDs, and their
      families were conducted. The origins of PM&R in Pakistan date to the 1960s, but
      the formal training program began only in 1997. There are only a few
      rehabilitation departments, and none have all the standard components of a
      rehabilitation team. The number of practicing rehabilitation consultants is 38.
      There are an estimated 1000 physical therapists and 150 occupational therapists.
      There is a need to increase the number of rehabilitation facilities
      significantly, staff them appropriately, and make them accessible to all who need
      them, including rural and remote regions. Discrimination should be addressed by
      education and legislation.

PMID- 21187219
TI  - Computer methods. Preface.

PMID- 21187220
TI  - Predicting fluorescence lifetimes and spectra of biopolymers.
AB  - Use of fluorescence in biology and biochemistry for imaging and characterizing
      equilibrium and dynamic processes is growing exponentially. Much progress has
      been made in the last few years on the microscopic understanding of the
      underlying principles of what controls the wavelength and quenching of
      fluorescence in biopolymers, both of which are central to the utility of
      fluorescent probes. This chapter is concerned with the quantitative microscopic
      understanding and prediction of the fluorescence wavelength and/or intensity of a
      fluorescent probe molecule attached to a biopolymer as revealed by hybrid quantum
      and classical mechanical computation procedures. The aim is not only to provide a
      recipe, but also even more importantly, to communicate the qualitative basic
      concepts of interpretation of fluorescence. These are surprisingly simple,
      although not broadly appreciated at this time. In addition, an effort has been
      made to show how these techniques have led to an emerging understanding of the
      relation between time-dependent wavelengths shifts due to solvent relaxation and
      population decay of conformational sub-ensembles.

PMID- 21187217
TI  - Psychosocial factors and adjustment to chronic pain in persons with physical
      disabilities: a systematic review.
AB  - OBJECTIVE: To systematically review the research findings regarding the
      associations between psychosocial factors and adjustment to chronic pain in
      persons with physical disabilities. DATA SOURCES: A key word literature search
      was conducted using articles listed in PubMed, PsychInfo, and CINAHL up to March
      2010, and manual searches were made of all retrieved articles to identify
      published articles that met the review inclusion criteria. STUDY SELECTION: To be
      included in the review, articles needed to (1) be written in English, (2) include
      adults with a physical disability who report having pain, (3) include at least 1
      measure of a psychosocial predictor domain, (4) include at least 1 criterion
      measure of pain or patient functioning, and (5) report the results of
      associations between the psychosocial factors and criterion measures used in the
      study. Twenty-nine studies met the inclusion criteria. DATA EXTRACTION: Three
      reviewers tabulated study details and findings. DATA SYNTHESIS: The disability
      groups studied included spinal cord injury (SCI), acquired amputation, cerebral
      palsy (CP), multiple sclerosis (MS), and muscular dystrophy (MD). Psychosocial
      factors were shown to be significantly associated with pain and dysfunction in
      all disability groups. The psychosocial factors most closely associated with pain
      and dysfunction across the samples included (1) catastrophizing cognitions; (2)
      task persistence, guarding, and resting coping responses; and (3) perceived
      social support and solicitous responding social factors. Pain-related beliefs
      were more strongly associated with pain and dysfunction in the SCI, CP, MS, and
      MD groups than in the acquired amputation group. CONCLUSIONS: The findings
      support the importance of psychosocial factors as significant predictors of pain
      and functioning in persons with physical disabilities. Clinical trials to test
      the efficacy of psychosocial treatments for pain and dysfunction are warranted,
      as are studies to determine whether psychosocial factors have a causal influence
      on pain and adjustment in these populations.

PMID- 21187221
TI  - Modeling of regulatory networks: theory and applications in the study of the
      Drosophila circadian clock.
AB  - Biological networks can be very complex. Mathematical modeling and simulation of
      regulatory networks can assist in resolving unanswered questions about these
      complex systems, which are often impossible to explore experimentally. The
      network regulating the Drosophila circadian clock is particularly amenable to
      such modeling given its complexity and what we call the clockwork orange (CWO)
      anomaly. CWO is a protein whose function in the network as an indirect activator
      of genes per, tim, vri, and pdp1 is counterintuitive--in isolated experiments,
      CWO inhibits transcription of these genes. Although many different types of
      modeling frameworks have recently been applied to the Drosophila circadian
      network, this chapter focuses on the application of continuous deterministic
      dynamic modeling to this network. In particular, we present three unique systems
      of ordinary differential equations that have been used to successfully model
      different aspects of the circadian network. The last model incorporates the newly
      identified protein CWO, and we explain how this model's unique mathematical
      equations can be used to explore and resolve the CWO anomaly. Finally, analysis
      of these equations gives rise to a new network regulatory rule, which clarifies
      the unusual role of CWO in this dynamical system.

PMID- 21187222
TI  - Strategies for articulated multibody-based adaptive coarse grain simulation of
      RNA.
AB  - Efficient modeling approaches are necessary to accurately predict large-scale
      structural behavior of biomolecular systems like RNA (ribonucleic acid). Coarse
      grained approximations of such complex systems can significantly reduce the
      computational costs of the simulation while maintaining sufficient fidelity to
      capture the biologically significant motions. However, given the coupling and
      nonlinearity of RNA systems (and effectively all biopolymers), it is expected
      that different parameters such as geometric and dynamic boundary conditions, and
      applied forces will affect the system's dynamic behavior. Consequently, static
      coarse-grained models (i.e., models for which the coarse graining is time
      invariant) are not always able to adequately sample the conformational space of
      the molecule. We introduce here the concept of adaptive coarse-grained molecular
      dynamics of RNA, which automatically adjusts the coarseness of the model, in an
      effort to more optimally increase simulation speed, while maintaining accuracy.
      Adaptivity requires two basic algorithmic developments: first, a set of
      integrators that seamlessly allow transitions between higher and lower fidelity
      models while preserving the laws of motion. Second, we propose and validate
      metrics for determining when and where more or less fidelity needs to be
      integrated into the model to allow sufficiently accurate dynamics simulation.
      Given the central role that multibody dynamics plays in the proposed framework,
      and the nominally large number of dynamic degrees of freedom being considered in
      these applications, a computationally efficient multibody method which lends
      itself well to adaptivity is essential to the success of this effort. A suite of
      divide-and-conquer algorithm (DCA)-based approaches is employed to this end.
      These algorithms have been selected and refined for this purpose because they
      offer a good combination of computational efficiency and modular structure.

PMID- 21187224
TI  - Inferring functional relationships and causal network structure from gene
      expression profiles.
AB  - Inferring functional relationships and network structure from the observed gene
      expression profiles can provide a novel insight into the working of the genes as
      a system or network as opposed to independent entities. Such networks may also
      represent possible causal relationships between a given set of genes, hence can
      prove to be a convenient abstraction of the underlying signaling mechanism. The
      discovery of functional relationships from the observed gene expression profiles
      does not rely on prior literature, hence useful in identifying undocumented
      relationships between a given set of genes. Several techniques have been proposed
      in the literature. The present study investigates the choice Granger causality
      (GC) and its extensions in modeling the network structure between a given pair of
      genes from their expression profiles. The impact of noise variance on GC
      relationships is investigated. VAR parameter estimation is proposed to obtain a
      finer insight into the functional relationships inferred using GC tests. The
      results are presented on synthetic networks generated from known vector
      autoregressive (VAR) models and those from cell-cycle gene expression profiles
      that can be modeled as a first-order bivariate VAR.

PMID- 21187223
TI  - Modeling loop entropy.
AB  - Proteins fold from a highly disordered state into a highly ordered one.
      Traditionally, the folding problem has been stated as one of predicting "the"
      tertiary structure from sequential information. However, new evidence suggests
      that the ensemble of unfolded forms may not be as disordered as once believed,
      and that the native form of many proteins may not be described by a single
      conformation, but rather an ensemble of its own. Quantifying the relative
      disorder in the folded and unfolded ensembles as an entropy difference may
      therefore shed light on the folding process. One issue that clouds discussions of
      "entropy" is that many different kinds of entropy can be defined: entropy
      associated with overall translational and rotational Brownian motion,
      configurational entropy, vibrational entropy, conformational entropy computed in
      internal or Cartesian coordinates (which can even be different from each other),
      conformational entropy computed on a lattice, each of the above with different
      solvation and solvent models, thermodynamic entropy measured experimentally, etc.
      The focus of this work is the conformational entropy of coil/loop regions in
      proteins. New mathematical modeling tools for the approximation of changes in
      conformational entropy during transition from unfolded to folded ensembles are
      introduced. In particular, models for computing lower and upper bounds on entropy
      for polymer models of polypeptide coils both with and without end constraints are
      presented. The methods reviewed here include kinematics (the mathematics of rigid
      body motions), classical statistical mechanics, and information theory.

PMID- 21187225
TI  - Numerical solution of the chemical master equation uniqueness and stability of
      the stationary distribution for chemical networks, and mRNA bursting in a gene
      network with negative feedback regulation.
AB  - In this work, we introduce a couple of algorithms to compute the stationary
      probability distribution for the chemical master equation (CME) of arbitrary
      chemical networks. We further find the conditions guaranteeing the algorithms'
      convergence and the unity and stability of the stationary distribution. Next, we
      employ these algorithms to study the mRNA and protein probability distributions
      in a gene regulatory network subject to negative feedback regulation. In
      particular, we analyze the influence of the promoter activation/deactivation
      speed on the shape of such distributions. We find that a reduction of the
      promoter activation/deactivation speed modifies the shape of those distributions
      in a way consistent with the phenomenon known as mRNA (or transcription)
      bursting.

PMID- 21187226
TI  - How molecular should your molecular model be? On the level of molecular detail
      required to simulate biological networks in systems and synthetic biology.
AB  - The recent advance of genetic studies and the rapid accumulation of molecular
      data, together with the increasing performance of computers, led researchers to
      design more and more detailed mathematical models of biological systems. Many
      modeling approaches rely on ordinary differential equations (ODE) which are based
      on standard enzyme kinetics. Michaelis-Menten and Hill functions are indeed
      commonly used in dynamical models in systems and synthetic biology because they
      provide the necessary nonlinearity to make the dynamics nontrivial (i.e., limit
      cycle oscillations or multistability). For most of the systems modeled, the
      actual molecular mechanism is unknown, and the enzyme equations should be
      regarded as phenomenological. In this chapter, we discuss the validity and
      accuracy of these approximations. In particular, we focus on the validity of the
      Michaelis-Menten function for open systems and on the use of Hill kinetics to
      describe transcription rates of regulated genes. Our discussion is illustrated by
      numerical simulations of prototype systems, including the Repressilator (a
      genetic oscillator) and the Toggle Switch model (a bistable system). We
      systematically compare the results obtained with the compact version (based on
      Michaelis-Menten and Hill functions) with its corresponding developed versions
      (based on "elementary" reaction steps and mass action laws). We also discuss the
      use of compact approaches to perform stochastic simulations (Gillespie
      algorithm). On the basis of these results, we argue that using compact models is
      suitable to model qualitatively biological systems.

PMID- 21187227
TI  - Computational modeling of biological pathways by executable biology.
AB  - "In silico" experiments (i.e., computer simulation) constitute an aid to
      traditional biological research, by allowing biologists to execute efficient
      simulations taking into consideration the data obtained in wet experiments and to
      generate new hypotheses, which can be later verified in additional wet
      experiments. In addition to being much cheaper and faster than wet experiments,
      computer simulation has other advantages: it allows us to run experiments in
      which several species can be monitored at the same time, to explore quickly
      various conditions by varying species and parameters in different runs, and in
      some cases to observe the behavior of the system at a greater level of detail
      than the one permitted by experimental techniques. In the past few years there
      has been a considerable effort in the computer science community to develop
      computational languages and software tools for modeling and analysing biochemical
      systems. Among the challenges which must be addressed in this context, there are:
      the definition of languages powerful enough to express all the relevant features
      of biochemical systems, the development of efficient algorithms to analyze models
      and interpret the results, and the implementation of modeling platforms which are
      usable by nonprogrammers. In this chapter, we focus on the use of computational
      modeling to the analysis of biochemical systems. Computational modeling, in
      conjunction with the use of formal intuitive modeling languages, enables
      biologists to define models using a notation very similar to the informal
      descriptions they commonly use, but formal and, hence, automatically executable.
      We describe the main features of the existing textual computational languages and
      the tool support available for model development and analysis.

PMID- 21187228
TI  - Computing molecular fluctuations in biochemical reaction systems based on a
      mechanistic, statistical theory of irreversible processes.
AB  - We discuss the quantification of molecular fluctuations in the biochemical
      reaction systems within the context of intracellular processes associated with
      gene expression. We take the molecular reactions pertaining to circadian rhythms
      to develop models of molecular fluctuations in this chapter. There are a
      significant number of studies on stochastic fluctuations in intracellular genetic
      regulatory networks based on single cell-level experiments. In order to
      understand the fluctuations associated with the gene expression in circadian
      rhythm networks, it is important to model the interactions of transcriptional
      factors with the E-boxes in the promoter regions of some of the genes. The
      pertinent aspects of a near-equilibrium theory that would integrate the
      thermodynamical and particle dynamic characteristics of intracellular molecular
      fluctuations would be discussed, and the theory is extended by using the theory
      of stochastic differential equations. We then model the fluctuations associated
      with the promoter regions using general mathematical settings. We implemented
      ubiquitous Gillespie's algorithms, which are used to simulate stochasticity in
      biochemical networks, for each of the motifs. Both the theory and the Gillespie's
      algorithms gave the same results in terms of the time evolution of means and
      variances of molecular numbers. As biochemical reactions occur far away from
      equilibrium-hence the use of the Gillespie algorithm-these results suggest that
      the near-equilibrium theory should be a good approximation for some of the
      biochemical reactions.

PMID- 21187229
TI  - Probing the input-output behavior of biochemical and genetic systems system
      identification methods from control theory.
AB  - A key aspect of the behavior of any system is the timescale on which it operates:
      when inputs change, do responses take milliseconds, seconds, minutes, hours,
      days, months? Does the system respond preferentially to inputs at certain
      timescales? These questions are well addressed by the methods of frequency
      response analysis. In this review, we introduce these methods and outline a
      procedure for applying this analysis directly to experimental data. This
      procedure, known as system identification, is a well-established tool in
      engineering systems and control theory and allows the construction of a
      predictive dynamic model of a biological system in the absence of any mechanistic
      details. When studying biochemical and genetic systems, the required experiments
      are not standard laboratory practice, but with advances in both our ability to
      measure system outputs (e.g., using fluorescent reporters) and our ability to
      generate precise inputs (with microfluidic chambers capable of changing cells'
      environments rapidly and under fine control), these frequency response methods
      are now experimentally practical for a wide range of biological systems, as
      evidenced by a number of successful recent applications of these techniques. We
      use a yeast G-protein signaling cascade as a running example, illustrating both
      theoretical concepts and practical considerations while keeping mathematical
      details to a minimum. The review aims to provide the reader with the tools
      required to design frequency response experiments for their own biological system
      and the background required to analyze and interpret the resulting data.

PMID- 21187230
TI  - Biochemical pathway modeling tools for drug target detection in cancer and other
      complex diseases.
AB  - In the near future, computational tools and methods based on the mathematical
      modeling of biomedically relevant networks and pathways will be necessary for the
      design of therapeutic strategies that fight complex multifactorial diseases.
      Beyond the use of pharmacokinetic and pharmacodynamic approaches, we propose here
      the use of dynamic modeling as a tool for describing and analyzing the structure
      and responses of signaling, genetic and metabolic networks involved in such
      diseases. Specifically, we discuss the design and construction of meaningful
      models of biochemical networks, as well as tools, concepts, and strategies for
      using these models in the search of potential drug targets. We describe three
      different families of computational tools: predictive model simulations as tools
      for designing optimal drug profiles and doses; sensitivity analysis as a method
      to detect key interactions that affect critical outcomes and other
      characteristics of the network; and other tools integrating mathematical modeling
      with advanced computation and optimization for detecting potential drug targets.
      Furthermore, we show how potential drug targets detected with these approaches
      can be used in a computer-aided context to design or select new drug molecules.
      All concepts are illustrated with simplified examples and with actual case
      studies extracted from the recent literature.

PMID- 21187231
TI  - Deterministic and stochastic simulation and analysis of biochemical reaction
      networks the lactose operon example.
AB  - A brief introduction to mathematical modeling of biochemical regulatory reaction
      networks is presented. Both deterministic and stochastic modeling techniques are
      covered with examples from enzyme kinetics, coupled reaction networks with
      oscillatory dynamics and bistability. The Yildirim-Mackey model for lactose
      operon is used as an example to discuss and show how deterministic and stochastic
      methods can be used to investigate various aspects of this bacterial circuit.

PMID- 21187232
TI  - Multivariate neighborhood sample entropy: a method for data reduction and
      prediction of complex data.
AB  - The analysis of large and complex databases poses many challenges. Such databases
      arise in health-services, electronic medical records, insurance, and other
      commercial data sources where both the number of observations and variables can
      be enormous. The problems are particularly acute in genomics and proteomics where
      the number of variables is typically much higher than the number of observations.
      Extant methods seek to balance the demands of making efficient use of the data
      with the need to maintain the flexibility required to detect complex
      relationships and interactions. To overcome some limitations of current methods,
      a novel analytical tool, Multivariate Neighborhood Sample Entropy (MN-SampEn) is
      introduced. It is a generalization of Sample Entropy to multivariate data that
      inherits many of Sample Entropy's desirable properties. In principle, it selects
      significant covariates without reference to an underlying model and provides
      predictions similar to those of k-Nearest-Neighbor methods, with fewer covariates
      required. However, adaptation to multivariate data requires that several
      additional optimization issues be addressed. Several optimization strategies are
      discussed and tested on a set of MALDI mass spectra. With some optimization
      strategies, MN-SampEn identified a reduced set of covariates and exhibited lower
      predictive error rates than k-Nearest Neighbors.

PMID- 21187233
TI  - Scaling differences of heartbeat excursions between wake and sleep periods.
AB  - We study the statistical properties of excursions in heart interbeat time series.
      An excursion is defined as the time employed by a walker to return to its mean
      value. We consider the homeostatic property of the heartbeat dynamics as a
      departing point to characterize the dynamics of excursions in beat-to-beat
      fluctuations. Scaling properties of excursions during wake and sleep periods from
      two groups are compared: 16 healthy subjects and 11 patients with congestive
      heart failure (CHF). We find that the cumulative distributions of excursions for
      both groups follow stretched exponential functions given by g(tau)~e(-atau(b))
      with different fitting parameters a and b, leading to different decaying rates.
      Our results show that the average characteristic scale associated with the
      excursion distributions is greater for healthy data compared to CHF patients
      whereas sleep-wake transitions are more significant for healthy data. Next, we
      explore changes in the distributions of excursions when considering (i) a shifted
      mean value to define an excursion and (ii) the sum of the kth excursion
      successor. Besides, the presence of temporal correlations in the excursions
      sequences is evaluated by means of the detrended fluctuation analysis. We observe
      the presence of long-range correlations for healthy subjects, whereas for the CHF
      group, correlations are described by two regimes; over short scales the
      fluctuations are close to uncorrelated noise, and for large scales the
      fluctuations reveal long-range correlations. Finally, we apply a stability
      analysis of excursions based on the Allan variance which reveals that healthy
      dynamics is more stable than heart failure excursions.

PMID- 21187234
TI  - Changepoint analysis for single-molecule polarized total internal reflection
      fluorescence microscopy experiments.
AB  - The experimental study of individual macromolecules has opened a door to
      determining the details of their mechanochemical operation. Motor enzymes such as
      the myosin family have been particularly attractive targets for such study, in
      part because some of them are highly processive and their "product" is spatial
      motion. But single-molecule resolution comes with its own costs and limitations.
      Often, the observations rest on single fluorescent dye molecules, which emit a
      limited number of photons before photobleaching and are subject to complex
      internal dynamics. Thus, it is important to develop methods that extract the
      maximum useful information from a finite set of detected photons. We have
      extended an experimental technique, multiple polarization illumination in total
      internal reflection fluorescence microscopy (polTIRF), to record the arrival time
      and polarization state of each individual detected photon. We also extended an
      analysis technique, previously applied to FRET experiments, that optimally
      determines times of changes in photon emission rates. Combining these
      improvements allows us to identify the structural dynamics of a molecular motor
      (myosin V) with unprecedented detail and temporal resolution.

PMID- 21187235
TI  - Inferring mechanisms from dose-response curves.
AB  - The steady state dose-response curve of ligand-mediated gene induction usually
      appears to precisely follow a first-order Hill equation (Hill coefficient equal
      to 1). Additionally, various cofactors/reagents can affect both the potency and
      the maximum activity of gene induction in a gene-specific manner. Recently, we
      have developed a general theory for which an unspecified sequence of steps or
      reactions yields a first-order Hill dose-response curve (FHDC) for plots of the
      final product versus initial agonist concentration. The theory requires only that
      individual reactions "dissociate" from the downstream reactions leading to the
      final product, which implies that intermediate complexes are weakly bound or
      exist only transiently. We show how the theory can be utilized to make
      predictions of previously unidentified mechanisms and the site of action of
      cofactors/reagents. The theory is general and can be applied to any biochemical
      reaction that has a FHDC.

PMID- 21187236
TI  - Spatial aspects in biological system simulations.
AB  - Mathematical models of the dynamical properties of biological systems aim to
      improve our understanding of the studied system with the ultimate goal of being
      able to predict system responses in the absence of experimentation. Despite the
      enormous advances that have been made in biological modeling and simulation, the
      inherently multiscale character of biological systems and the stochasticity of
      biological processes continue to present significant computational and conceptual
      challenges. Biological systems often consist of well-organized structural
      hierarchies, which inevitably lead to multiscale problems. This chapter
      introduces and discusses the advantages and shortcomings of several simulation
      methods that are being used by the scientific community to investigate the
      spatiotemporal properties of model biological systems. We first describe the
      foundations of the methods and then describe their relevance and possible
      application areas with illustrative examples from our own research. Possible ways
      to address the encountered computational difficulties are also discussed.

PMID- 21187237
TI  - Computational approaches to modeling viral structure and assembly.
AB  - The structures of biological macromolecules and macromolecular assemblies can be
      experimentally determined by X-ray crystallography, nuclear magnetic resonance
      (NMR), and cryo-electron microscopy (cryo-EM). The refinement of such structures
      is a difficult task, because of the size of the experimental data sets, and
      because of the very large number of degrees of freedom. Molecular modeling tools
      particularly those based on the principles of molecular mechanics-have long been
      employed to assist in the refinement of macromolecular structures. Molecular
      mechanics methods are also used to generate de novo models when there are only
      limited experimental data available. Ideally, such models provide information on
      structure-function relationships, and on the thermodynamic and kinetic properties
      of the system of interest. Here, we summarize some of the molecular mechanics
      methods used to investigate questions of viral structure and assembly, including
      both all-atom and coarse-grained approaches.

PMID- 21187239
TI  - Computational design of intermolecular stability and specificity in protein self
      assembly.
AB  - The ability to engineer novel proteins using the principles of molecular
      structure and energetics is a stringent test of our basic understanding of how
      proteins fold and maintain structure. The design of protein self-assembly has the
      potential to impact many fields of biology from molecular recognition to cell
      signaling to biomaterials. Most progress in computational design of protein self
      assembly has focused on alpha-helical systems, exploring ways to concurrently
      optimize the stability and specificity of a target state. Applying these methods
      to collagen self-assembly is very challenging, due to fundamental differences in
      folding and structure of alpha- versus triple-helices. Here, we explore various
      computational methods for designing stable and specific oligomeric systems, with
      a focus on alpha-helix and collagen self-assembly.

PMID- 21187238
TI  - ROSETTA3: an object-oriented software suite for the simulation and design of
      macromolecules.
AB  - We have recently completed a full re-architecturing of the ROSETTA molecular
      modeling program, generalizing and expanding its existing functionality. The new
      architecture enables the rapid prototyping of novel protocols by providing easy
      to-use interfaces to powerful tools for molecular modeling. The source code of
      this rearchitecturing has been released as ROSETTA3 and is freely available for
      academic use. At the time of its release, it contained 470,000 lines of code.
      Counting currently unpublished protocols at the time of this writing, the source
      includes 1,285,000 lines. Its rapid growth is a testament to its ease of use.
      This chapter describes the requirements for our new architecture, justifies the
      design decisions, sketches out central classes, and highlights a few of the
      common tasks that the new software can perform.

PMID- 21187240
TI  - Differential analysis of 2D gel images.
AB  - Two-dimensional polyacrylomide gel electrophoresis remains a popular and powerful
      tool for identifying proteins that are differentially expressed across treatment
      conditions. Due to the overwhelming number of proteins and the tremendous
      variation shown in gel images, the differential analysis of 2D gel images is
      challenging. While commercial software packages are available for such analysis,
      they require considerable human intervention for spot detection and matching.
      Moreover, the quantitative comparison across groups of gels is based on simple
      classical tests that often do not fully account for the experimental design. We
      developed software with a graphical user interface, RegStatGel, which implements
      a novel statistical algorithm for identifying differentially expressed proteins.
      Unlike current commercial software packages, it is free, open-source, easy to use
      and almost fully automated. It also provides more advanced statistical tools.
      More importantly, by using a master watershed map, RegStatGel bypasses the spot
      matching procedure, which is a time-consuming bottleneck in gel image analysis.
      The software is freely available for academic use and has been tested in Matlab
      7.01 under Windows XP. Detailed instructions on how to use RegStatGel to analyze
      2D gel images are provided.

PMID- 21187245
TI  - Technology and innovation in arthroscopic and related surgery.

PMID- 21187242
TI  - Ethanol induces second-order aversive conditioning in adolescent and adult rats.
AB  - Alcohol abuse and dependence are considered public health problems, with an
      etiological onset often occurring during late childhood and adolescence, and
      understanding age-related differences in ethanol sensitivity is important. Low to
      moderate ethanol doses (0.5 and 2.0 g/kg, intragastrically [i.g.]) induce single
      trial, appetitive second-order place conditioning (SOC) in adolescent, but not
      adult, rats. Recent studies have demonstrated that adolescents may be less
      sensitive than adults to the aversive properties of ethanol, reflected by
      conditioned taste aversion. The present study assessed the aversive motivational
      effects of high-dose ethanol (3.0 and 3.25 g/kg, i.g., for adolescents and
      adults, respectively) using SOC. Experiment 1 revealed similar blood and brain
      ethanol levels in adolescent and adult rats given 3.0 and 3.25 g/kg ethanol,
      respectively. In Experiment 2, animals received ethanol or vehicle paired with
      intraoral pulses of sucrose (conditioned stimulus 1 [CS1]). After one, two, or
      three conditioning trials, the rats were presented with the CS1 while in a
      distinctive chamber (CS2). When tested for CS2 preference, ethanol-treated
      animals exhibited reduced preference for the CS2 compared with controls. This
      result, indicative of ethanol-mediated aversive place conditioning, was similar
      for adolescents and adults; for females and males; and after one, two, or three
      training trials. In conjunction with previous results, the present study showed
      that, in adolescent rats subjected to SOC, ethanol's hedonic effects vary from
      appetitive to aversive as the ethanol dose increases. Adolescent and adult
      animals appear to perceive the postingestive effects of high-dose ethanol as
      similarly aversive when assessed by SOC.

PMID- 21187247
TI  - Chondrolysis of the glenohumeral joint: level of evidence and additional
      analyses.

PMID- 21187249
TI  - Editors' note.

PMID- 21187250
TI  - Arthroscopic glenoid osteochondral allograft reconstruction without subscapularis
      takedown: technique and literature review.
AB  - Failure to address glenoid deficiency/osteochondral defects can lead to
      persistent shoulder instability despite a surgical stabilization procedure. In
      patients with significant glenoid bone loss, osteoarticular allograft
      transplantation has the potential benefit of restoring normal glenohumeral
      anatomy. It may also reduce the risk of recurrent instability and permit near
      normal postoperative range of motion while avoiding the complications of
      nonanatomic reconstruction techniques. Numerous open methods of anatomic glenoid
      reconstruction have been described, including the use of iliac crest autograft,
      distal tibia allograft, and glenoid allograft. Our purpose is to review the
      literature regarding the surgical treatment of glenoid bone deficiency. We also
      describe a novel technique of arthroscopic anteroinferior glenoid reconstruction
      using glenoid osteochondral allograft without subscapularis takedown. The
      potential risks and benefits of our technique are also discussed.

PMID- 21187251
TI  - Complication of the use of a radiofrequency device in arthroscopic shoulder
      surgery: second-degree burn of the shoulder girdle.
AB  - Radiofrequency ablation (RF) energy devices are increasingly being used in
      arthroscopic surgery. This is a case report of a 53-year-old man who had second
      degree burns of the shoulder and chest wall as a result of fluid overheating due
      to RF. During an extensive arthroscopic bursal dissection of the left shoulder,
      the suction device on the RF wand and the valve was left open, allowing fluid to
      drip onto the chest and arm of the patient. Three days after his surgery, on his
      first postoperative visit, the dressings were removed, and the patient was noted
      to have severe blistering on the lateral aspect of his arm and on the
      anterolateral aspect of his left chest wall. One year after the surgery, he still
      had residual scarring that was only mildly intermittently pruritic. The use of RF
      during arthroscopic surgery is very useful clinically; however, it is important
      to have a strict understanding of the potential hazards the thermal energy can
      cause to the surrounding soft tissue.

PMID- 21187252
TI  - Dermal burns associated with bipolar radiofrequency ablation in the subacromial
      space.
AB  - This article presents iatrogenic dermal burn injury as a complication of using a
      vented bipolar radiofrequency (RF) ablative device in shoulder arthroscopy. We
      have encountered 4 patients who have sustained second-degree skin burns after
      shoulder arthroscopy. The burns occurred from arthroscopic shoulder surgeries
      performed from 2004 to 2008. In each case a vented bipolar RF device was used to
      help perform a subacromial decompression. The burns appeared to be the result of
      heated effluent from the outflow tubing of the RF device exposed to the skin of
      the patients. This case report shows that care should be taken to avoid exposing
      patients to the elevated temperatures of bipolar RF device effluent to reduce the
      risk of dermal burn injury.

PMID- 21187253
TI  - Journal of cardiology, official journal of the Japanese college of cardiology.

PMID- 21187254
TI  - Blood pressure 1 year after stroke: the need to optimize secondary prevention.
AB  - Lowering blood pressure (BP) in stroke survivors reduces the risk of recurrent
      stroke. We tested the hypothesis that a nurse-led nonpharmacologic intervention
      would lower the BP of participants in an intervention group compared with a
      control group. A total of 349 patients who had sustained acute stroke or
      transient ischemic attack were randomly assigned to either usual care or to 4
      home visits by a nurse. During the visits, the nurse measured and recorded BP and
      provided individually tailored counseling on a healthy lifestyle. A total of 303
      patients completed the 1-year follow up. No change in systolic BP was noted in
      either the intervention group or the control group. Because of an increase in
      diastolic BP in the control group (P = .03), a difference in mean diastolic BP
      between the 2 groups was found at follow-up (P = .007). Mean BP at follow-up was
      139/82 mm Hg in the intervention group and 142/86 mm Hg in the control group.
      Linear regression analysis demonstrated that BP at the point of discharge was the
      strongest predictor of BP 1 year later (P < .0001). The proportion of patients on
      antihypertensive medication increased in the intervention group (P = .002).
      Patients were compliant with antihypertensive therapy, and 92% of the
      hypertensive patients in the intervention group followed the advice to see a
      general practitioner (GP) for BP checkups. At follow-up, 187 patients (62%) were
      hypertensive, with no difference in the rate of hypertension seen between the
      groups. Our data indicate that home visits by nurses did not result in a lowering
      of BP. Patients complied with antihypertensive therapy and GP visits in the case
      of hypertension. Nonetheless, the majority of patients were hypertensive at the 1
      year follow up.

PMID- 21187255
TI  - Clinical characteristics and outcomes in carotid endarterectomy for internal
      carotid artery stenosis in a Japanese population: 10-year microsurgical
      experience.
AB  - Few studies have explored the significance of carotid endarterectomy (CEA) in
      long-term prognosis in Japanese patients. In the present study, we precisely
      elucidated the demographic and radiologic data, surgical morbidity and mortality,
      and long-term outcome in 135 Japanese patients who underwent a total of 142 CEAs
      due to 70%-99% stenosis of the internal carotid artery at our hospitals over a 10
      year period. The prevalence of risk factors was similar to those found in
      previous studies in Western countries. Surgical mortality (0.7%) and morbidity
      (2.8%) were relatively low. Blood flow studies done immediately after CEA
      revealed postoperative hyperperfusion in 8 patients (5.6%), but none of these
      patients exhibited related symptoms. Over the mean follow-up period of 38.7
      months, a total of 9 patients died (6.7%), due mainly to malignancies.
      Cerebrovascular events occurred in 12 patients (8.5%), including ipsilateral
      ischemic stroke in 2 (1.4%). In addition, 11 patients (8.2%) developed vascular
      disorders in other organs, including coronary artery disease and chronic renal
      failure. Follow-up radiologic examination revealed restenosis of >50% in 3
      carotid arteries (2.1%). Stenosis of the contralateral carotid arteries
      progressed to >70% in 12 patients (9.2%). This study strongly suggests that
      microsurgical CEA is feasible and effective in preventing subsequent ipsilateral
      ischemic stroke in Japanese patients; however, long-term medical and radiologic
      surveillance is essential to reduce the incidence of ischemic stroke in other
      areas and of vascular disorders in other organs to improve prognosis.

PMID- 21187257
TI  - Acute heart failure guidelines: moving in the right direction?

PMID- 21187256
TI  - Significance of clinical-diffusion mismatch in hyperacute cerebral infarction.
AB  - In recent years, patient selection for intravenous tissue plasminogen activator
      (t-PA) therapy based on clinical-diffusion mismatch (CDM) has been closely
      examined. We investigated the relationship between prognosis and CDM in patients
      with hyperacute cerebral infarction within 3 hours of onset and compared CDM with
      diffusion-perfusion mismatch (DPM). Of 122 patients with hyperacute cerebral
      infarction who visited the hospital within 3 hours of onset between April 2007
      and November 2008, 85 patients with cerebral infarction in the anterior
      circulation who underwent head magnetic resonance imaging diffusion-weighted
      imaging (DWI)/magnetic resonance angiography (MRA) (51 men and 34 women; average
      age, 74 +/- 10 years) were enrolled. Seventeen of these patients underwent CT
      perfusion imaging. CDM-positive cases were those with a National Institute of
      Health Stroke Scale (NIHSS) score >= 8 and a DWI-Alberta Stroke Program Early CT
      Score (DWI-ASPECTS) >= 8; CDM-negative cases were those with an NIHSS score >= 8
      and an ASPECTS-DWI < 8. The other patients were classified as belonging to the
      NIHSS score < 8 group. Of the 32 CDM-positive cases, 10 received t-PA infusion.
      These patients had markedly higher modified Rankin Scale scores 90 days after
      onset compared with the 22 patients who did not receive t-PA infusion. The 8 CDM
      positive cases included 4 DPM-positive cases and 4 DPM-negative cases, and a
      discrepancy was confirmed between CDM and DPM. In all DPM-positive cases, MRA
      confirmed lesions in major intracranial arteries. CDM may enable more accurate
      prediction of outcomes in patients with hyperacute cerebral infarction. In
      addition, the combination of CDM findings and MRA findings (stenosis or occlusion
      in major intracranial arteries) may be an alternative to DPM for determining the
      indications for IV t-PA therapy in patients with hyperacute cerebral infarction.

PMID- 21187258
TI  - CHAMPION trial rationale and design: the long-term safety and clinical efficacy
      of a wireless pulmonary artery pressure monitoring system.
AB  - BACKGROUND: Decompensated heart failure (HF) is associated with unacceptable
      morbidity and mortality risks. Recent implantable technology advancements allow
      frequent filling pressure monitoring and provide insight into HF pathophysiology
      and a new tool for HF management. METHODS: The CHAMPION trial is a prospective,
      multicenter, randomized, single-blind clinical trial testing the hypothesis that
      HF management guided by frequently assessed pulmonary artery pressures is
      superior to traditional methods. A total of 550 subjects with New York Heart
      Association (NYHA) functional class III HF were enrolled at 64 sites in the
      United States. All subjects received the CardioMEMS HF sensor as a permanent
      pulmonary artery implant and were randomized to the treatment or the control
      group before discharge. The treatment group received traditional HF management
      guided by hemodynamic information from the sensor. The control group received
      traditional HF disease management. Safety endpoints include freedom from
      device/system-related complications and freedom from HF sensor failure at 6
      months. The efficacy endpoint is a reduction in the rate of HF-related
      hospitalizations in the treatment group versus the control group at 6 months.
      CONCLUSIONS: The CHAMPION trial will investigate the safety and clinical efficacy
      of the CardioMEMS hemodynamic monitoring system and may establish this management
      strategy as a new paradigm for the medical management of patients with
      symptomatic HF.

PMID- 21187259
TI  - Design of the Multi-Sensor Monitoring in Congestive Heart Failure (MUSIC) study:
      prospective trial to assess the utility of continuous wireless physiologic
      monitoring in heart failure.
AB  - BACKGROUND: Remote monitoring of heart failure (HF) patients may help in the
      early detection of acute HF decompensation before the onset of symptoms.
      Appropriate early intervention in these patients may reduce HF-related
      hospitalizations and costs. METHODS: The MUSIC (Multi-Sensor Monitoring in
      Congestive Heart Failure) study comprises 2 multicenter nonrandomized phases
      (MUSIC-Development and MUSIC-Validation) designed to develop and validate an
      algorithm for the prediction of acute HF decompensation using multiple
      physiologic signals obtained from an external, adherent, multisensor system
      capable of intermittent transmission of physiologic signals. Data obtained from
      MUSIC-Development will be used to develop the algorithm to predict HF
      decompensation. The algorithm will be validated in MUSIC-Validation with the
      objectives of >= 60% sensitivity for correctly predicting an acute HF event, a
      false-positive patient status signal rate of <= 1.0 per patient-year, and a
      safety endpoint of <= 5% of patients experiencing significant adverse skin
      conditions related to the prolonged wearing of the adherent device. A total of
      542 patients in New York Heart Association functional class III-IV HF, with
      ejection fraction <= 40% and a recent HF admission, are enrolled in MUSIC
      Development (n = 180) and MUSIC-Validation (n = 362). All patients are remotely
      monitored for 90 days using the Corventis multisensor system that transmits
      bioimpedance, electrocardiogram, and accelerometer data. RESULTS: The MUSIC study
      has completed patient enrollment and follow-up in both phases. Once algorithm
      development is complete from the MUSIC-Development phase, the sequestered data
      set from the MUSIC-Validation phase will be used for algorithm validation.

PMID- 21187260
TI  - Symptoms characteristic of heart failure among CKD patients without diagnosed
      heart failure.
AB  - BACKGROUND: Epidemiological studies typically diagnose heart failure (HF) at the
      time of hospitalization, and have not evaluated the prevalence of HF symptoms in
      CKD patients without a prior HF diagnosis. METHODS AND RESULTS: We modified the
      Kansas City Cardiomyopathy Questionnaire (KCCQ) to detect and quantify symptoms
      characteristic of HF (dyspnea, edema, and fatigue) among 2883 chronic kidney
      disease (CKD) patients without diagnosed heart failure in the Chronic Renal
      Insufficiency Cohort (CRIC). The KCCQ is a 23-item instrument that quantifies the
      impact of dyspnea, fatigue, and edema on physical, social, and emotional
      functions (scored 0 to 100). The median KCCQ score was 92, and 25% had KCCQ
      scores <75. Compared with cystatin C-based estimated glomerular filtration rate
      >50 mL.min.1.73 m(2) (reference), estimated glomerular filtration rate 40 to 50,
      30 to 40, and <30 were independently associated with lower KCCQ scores (<75);
      adjusted odds ratios and (95% CI): 1.38 (1.06-1.78), 1.39 (1.09-1.82), and 2.15
      (1.54-3.00), respectively. Lower hemoglobin (Hb) levels also had independent
      associations with KCCQ <75: Hb >14 g/dL (reference), Hb 13 to 14 g/dL (1.03; 0.76
      1.40), Hb 12 to 13 g/dL (1.41; 1.04-1.91), Hb 11 to 12 g/dL (1.56; 1.12-2.16);
      and Hb <1 g/dL (1.65; 1.15-2.37). CONCLUSION: CKD patients without diagnosed HF
      have a substantial burden of symptoms characteristic of HF, particularly among
      those with lower estimated glomerular filtration rate and hemoglobin levels.

PMID- 21187261
TI  - Association of resistin with heart failure and mortality in patients with stable
      coronary heart disease: data from the heart and soul study.
AB  - BACKGROUND: Resistin is a pro-inflammatory signaling molecule that is thought to
      contribute to atherosclerosis. We sought to evaluate whether resistin is
      predictive of worse cardiovascular outcomes among ambulatory patients with stable
      coronary heart disease (CHD). METHODS AND RESULTS: We measured baseline serum
      resistin in 980 participants with documented CHD. After a mean follow-up of 6.1
      (range, 0.1 to 9.0) years, 358 (36.5%) were hospitalized for myocardial
      infarction or heart failure or had died. As compared with participants who had
      resistin levels in the lowest quartile, those with resistin levels in the highest
      quartile were at an increased risk of heart failure (hazard ratio [HR], 2.06; 95%
      confidence interval [CI], 1.26-3.39) and death (HR, 1.56; 95% CI, 1.11-2.18),
      adjusted for age, sex, and race. Further adjustments for obesity, hypertension,
      insulin resistance, dyslipidemia, and renal dysfunction eliminated these
      associations. Resistin levels were not associated with an increased risk of non
      fatal myocardial infarction (unadjusted HR, 1.18; 95% CI, 0.68-2.05).
      CONCLUSIONS: Elevated serum resistin is associated with higher rates of mortality
      and hospitalization for heart failure. However, this appears to be explained by
      the association of resistin with traditional measures of cardiovascular risk.
      Thus, serum resistin does not add prognostic information among high-risk persons
      with established CHD.

PMID- 21187262
TI  - Prognostic value of cystatin C on admission in heart failure with preserved
      ejection fraction.
AB  - BACKGROUND: Cystatin C has emerged as a new biomarker of renal function that has
      been found to predict adverse cardiovascular outcomes, especially heart failure
      (HF). Evidence of the usefulness of cystatin C in patients with heart failure
      with preserved ejection fraction (HFPEF) remains sparse. It is hypothesized that
      serum cystatin C levels in HFPEF has prognostic value. METHODS AND RESULTS:
      Cystatin C, urea nitrogen, creatinine, and N-terminal proBNP-type natriuretic
      peptide levels were measured on admission in 218 consecutive patients with HF and
      left ventricular ejection fraction >45%, as measured by Doppler echocardiography.
      The primary end point was all-cause mortality and/or readmission at 1 year. We
      determined the adjusted hazard ratio (HR) by Cox regression model. During the 1
      year follow-up period, 70 patients (32.2%) died, and 126 patients (57.8%) died
      and/or required rehospitalization. Serum cystatin C levels by quartiles were
      associated with increased risk for adverse events. Kaplan-Meier survival curves
      showed significantly increased primary end point with each quartile of cystatin C
      (log rank <0.001). Patients in the highest quartile of cystatin C level were at
      increased adjusted risk for the primary end point (HR 3.40; 95% confidence
      interval [CI] 1.86-6.21; P < .0001) and all-cause mortality (HR 8.14; 95% CI 1.21
      23.26; P < .01). Furthermore, high serum cystatin C levels were also associated
      with poor prognosis despite normal or mildly reduced renal function. CONCLUSIONS:
      Serum cystatin C level on admission in patients with HFPEF is a strong and
      independent predictor of an unfavorable outcome. This relationship remains in
      patients without advanced renal dysfunction.

PMID- 21187263
TI  - Prognostic value of left and right coronary flow reserve assessment in
      nonischemic dilated cardiomyopathy by transthoracic Doppler echocardiography.
AB  - BACKGROUND: Coronary flow reserve (CFR) in the left anterior descending artery
      (LAD) can be reduced in nonischemic dilated cardiomyopathy (DCM). The aim of this
      study was to assess the prognostic value of CFR in LAD and in the posterior
      descending artery (PD) in DCM patients. METHODS: Seventy-two DCM patients (44
      men, mean age 64 +/- 13 years) underwent dipyridamole (0.84 mg/kg in 6 minutes)
      stress echo. CFR was defined as the ratio between maximal vasodilation and rest
      peak diastolic flow velocity in LAD and PD. RESULTS: CFR was abnormal in LAD in
      42 out of 72 patients and in PD in 31 out of 55. All patients completed the
      clinical follow-up, and 56 patients completed the echocardiographic follow-up.
      During median follow-up of 42 months, 33 events (7 deaths, 26 major cardiac
      events) occurred. Event rate was markedly higher for patients with reduced CFR
      compared with DCM patients with normal CRF in LAD (0 vs 19 events; P < .001) and
      in PD (1 vs 13 events; P < .001). CFR in LAD and in PD were significantly related
      to the change in end-systolic volume during follow-up (r = -0.481, P < .001; and
      r = -0.407, P = .028; respectively). Preserved CFR in both LAD and PD was
      associated with better (P < .0001) event-free survival compared with abnormal CFR
      (log rank: 28.1; P < .0001). CONCLUSIONS: In DCM patients, impairment of CFR in
      LAD and PD is related to a worse outcome; CFR impairment is more relevant when it
      occurs in LAD. PD evaluation may be redundant and time-consuming, because the
      additive value is small and the feasibility suboptimal.

PMID- 21187264
TI  - Educational level and the quality of life of heart failure patients: a
      longitudinal study.
AB  - BACKGROUND: Lower education in heart failure (HF) patients is associated with
      high levels of anxiety, limited physical functioning, and an increased risk of
      hospitalization. We examined whether educational level is related to longitudinal
      differences in quality of life (QoL) in HF patients. METHODS AND RESULTS: This
      research is a substudy of the Coordinating study evaluating Outcomes of Advising
      and Counselling in Heart failure (COACH). QoL of 553 HF patients (mean age 69,
      38% female, mean left ventricular ejection fraction 33%) was assessed during
      their hospitalization and at 4 follow-up measurements after discharge. In total
      32% of the patients had very low, 24% low, 32% medium, and 12% high education.
      Patients with low educational levels reported the worst QoL. Significant
      differences between educational groups (P < .05) were only reported in physical
      functioning, social functioning, energy/fatigue, pain, and limitations in role
      functioning related to emotional problems. Longitudinal results show that a
      significantly higher proportion of high-educated patients improved in functional
      limitations related to emotional problems over time compared with lower-educated
      patients (P < .05). CONCLUSIONS: Patients with low educational levels reported
      the worst physical and functional condition. High-educated patients improved more
      than the other patients in functional limitations related to emotional problems
      over time. Low-educated patients may require different levels of intervention to
      improve their physical and functional condition.

PMID- 21187265
TI  - Hospitalization epidemic in patients with heart failure: risk factors, risk
      prediction, knowledge gaps, and future directions.
AB  - Patients with heart failure (HF) are hospitalized over a million times annually
      in the United States. Hospitalization marks a fundamental change in the natural
      history of HF, leading to frequent subsequent rehospitalizations and a
      significantly higher mortality compared with nonhospitalized patients. Three
      fourths of all HF hospitalizations are due to exacerbation of symptoms in
      patients with known HF. One-half of hospitalized HF patients experience
      readmission within 6 months. Preventing HF hospitalization and rehospitalization
      is important to improve patient outcomes and curb health care costs. To implement
      cost-effective strategies to contain the HF hospitalization epidemic, optimal
      schemes to identify high-risk individuals are needed. In this review, we describe
      the risk factors that have been associated with hospitalization risk in HF and
      the various multimarker risk prediction schemes developed to predict HF
      rehospitalization. We comment on areas that represent gaps in our knowledge or
      difficulties in interpretation of the current literature, representing
      opportunities for future research. We also discuss issues with using HF
      readmission rate as a quality indicator.

PMID- 21187266
TI  - Prevalence of stroke in systolic heart failure.
AB  - BACKGROUND: Heart disease is a major independent risk factor for stroke, ranking
      third after age and hypertension. Heart failure (HF) patient constitutes an
      important subgroup of patients with stroke, because of their poor outcome and
      high rates of mortality and stroke recurrence. We examined the prevalence of
      stroke in patients with heart failure from 3 different geographic regions.
      METHODS AND RESULTS: We compared the prevalence of self-reported history of
      stroke in participants with systolic HF from 3 different geographic regions
      (Houma, LA; Miami, FL; and Tbilisi, Georgia, Eastern Europe). We examined the
      prevalence of stroke/adjusting for patient demographic and health
      characteristics. Stroke prevalence was reported by 79 (7.8%) of 1017 participants
      from Louisiana, 51 (9.2%) of 556 participants from Florida, and 5 (1.3%) of 383
      participants from Georgia. After multivariable adjustment, the prevalence of
      stroke was significantly lower in Georgia compared to Florida and Louisiana
      sites. Patients on beta-blocker medication were 3.58 times (95% CI 1.96-6.55)
      more likely to report stroke compared to those without beta-blockers (*2 = 19.5,
      P <= .0001). There were significantly fewer participants on beta-blockers from
      Georgia (7%) compared to participants from Florida (87%) and Louisiana (94%; (*2
      = 24.3, P<.001). CONCLUSIONS: Self-reported stroke prevalence in participants
      with HF was not consistent among the 3 sites. These differences in prevalence may
      in part be explained by the lower reported use of beta-blockers in the Georgia
      site. Longitudinal studies are needed to determine whether beta-blockers increase
      the risk of stroke in HF population.

PMID- 21187269
TI  - Tradition of excellence continues.

PMID- 21187270
TI  - Analgesic prescribing errors and associated medication characteristics.
AB  - Medication errors involving analgesics, including mistakes in prescribing, are a
      major contributor to suboptimal therapeutic outcomes and preventable adverse
      patient events. A systematic evaluation of 2,044 prevented (near-miss) analgesic
      prescribing errors detected in a teaching hospital was performed to better
      understand these errors and contributing error-prone analgesic medication
      characteristics. The overall detected error rate was 2.87 errors per 1,000
      analgesic orders, with the error rate more than twice as high in pediatric
      patients than in adults. Error rates varied widely between drugs, dosage forms,
      and routes of administration, but there was general consistency of error rates
      within drug groups with similar characteristics. Commonly prescribed medications
      were associated with the most errors, but less frequently prescribed agents had
      higher error rates. A number of factors were found to contribute to errors, and
      the following characteristics contributed to 40% of errors: availability in dose
      forms for multiple routes of administration; modified dosage forms; atypical
      dosage regimens; sound-alike drug names; and analgesics used on an ongoing
      scheduled basis. PERSPECTIVE: Identifiable analgesic product characteristics and
      uses are associated with higher risk for errors. The findings of this study can
      guide patient and caregiver education, and can be incorporated into medication
      safety strategies to reduce patient risk from analgesic errors.

PMID- 21187267
TI  - Extracellular matrix of collagen modulates intracellular calcium handling and
      electrophysiological characteristics of HL-1 cardiomyocytes with activation of
      angiotensin II type 1 receptor.
AB  - BACKGROUND: Myocardial fibrosis plays a critical role in heart failure, resulting
      in cardiac structural and electrical remodeling which can induce atrial
      arrhythmias. Collagen is the major element of fibrosis. However, it is not clear
      whether collagen can directly regulate the calcium homeostasis and the
      electrophysiologic characteristics of cardiomyocytes. The aim of this study was
      to determine the effects of collagen on calcium homeostasis and the electrical
      properties of atrial cardiomyocytes. METHODS AND RESULTS: HL-1 cardiomyocytes
      were cultured with and without collagen type I (1 or 10 MUg/mL) or losartan (10
      MUmol/L). Whole-cell clamp, indo-1 fluorescence, and Western blotting were used
      to evaluate the action potential (AP) and ionic currents, intracellular calcium
      homeostasis, and calcium regulatory proteins. Compared with the control samples,
      there was no significant difference in collagen (1 MUg/mL)-treated HL-1
      cardiomyocytes. However, collagen (10 MUg/mL)-treated HL-1 cardiomyocytes
      exhibited larger intracellular calcium ([Ca(2+)](i)) transients by 113% and a
      larger sarcoplasmic reticulum calcium content by 86%. Collagen (10 MUg/mL)
      treated HL-1 cardiomyocytes had higher expression of sarcoplasmic reticulum
      ATPase (SERCA2a) and Thr17-phosphorylated phospholamban but similar protein
      expressions of the Na(+)/Ca(2+) exchanger and ryanodine receptor. Collagen (10
      MUg/mL)-treated HL-1 cardiomyocytes (n = 11) had larger AP amplitude (104 +/- 5
      vs 83 +/- 7 mV; P < .05), and shorter 90% of AP duration (25 +/- 2 vs 33 +/- 2
      ms, P < .05) than control cells (n = 11). Moreover, collagen (10 MUg/mL)-treated
      HL-1 cells had larger I(to) and I(Ksus) values than control cells. The
      administration of losartan (10 MUmol/L) attenuated collagen-induced changes in
      [Ca(2+)](i) transients, [Ca(2+)](i) stores, AP morphology, ionic currents,
      SERCA2a, and Thr17-phosphorylated phospholamban expressions. CONCLUSIONS: This
      study demonstrates that collagen can directly modulate the calcium dynamics and
      electrical activities of atrial cardiomyocytes, which are associated with the
      renin-angiotensin system. These findings suggest a critical role of collagen in
      electrical remodeling during fibrosis.

PMID- 21187271
TI  - A personal perspective of the peer review process for plastic publications.

PMID- 21187272
TI  - Mu-opioid and noradrenergic alpha(2)-adrenoceptor contributions to the effects of
      tapentadol on spinal electrophysiological measures of nociception in nerve
      injured rats.
AB  - Multiple pathological mechanisms at multiple sensory sites may underlie the pain
      that follows nerve injury. This provides a basis for recommending more than one
      agent, either sequentially or in combination, for its treatment. According to
      this premise, new drugs that combine different mechanisms of analgesic action in
      a single molecule are gaining momentum, such as tapentadol which stimulates mu
      opioid receptors (MOR) and acts as a noradrenaline reuptake inhibitor (NRI) in
      the CNS. Tapentadol is currently indicated for treating moderate to severe acute
      and severe chronic pain, and here we demonstrate its efficacy in an animal model
      of ongoing neuropathic pain. In particular, we performed a series of in vivo
      electrophysiological tests in spinal nerve ligated and sham-operated rats to show
      that systemic tapentadol (1 and 5mg/kg) dose-dependently reduced evoked responses
      of spinal dorsal horn neurones to a range of peripheral stimuli, including brush,
      punctate mechanical and thermal stimuli. Furthermore, we showed that spinal
      application of the selective alpha(2)-adrenoceptor antagonist atipamezole, or
      alternatively the mu-opioid receptor antagonist naloxone, produced near complete
      reversal of tapentadol's inhibitory effects, which suggests not only that the
      spinal cord is the key site of tapentadol's actions, but also that no
      pharmacology other than MOR-NRI is involved in its analgesia. Moreover, according
      to the extent that the antagonists reversed tapentadol's inhibitions in sham and
      SNL rats, we suggest that there may be a shift from predominant opioid inhibitory
      mechanisms in control animals, to predominant noradrenergic inhibition in
      neuropathic animals.

PMID- 21187275
TI  - Tackling tuberculosis in London's homeless population.

PMID- 21187276
TI  - Stopping traffic.

PMID- 21187280
TI  - Positive effects of Forskolin (stimulator of lipolysis) treatment on cryosurvival
      of in vitro matured porcine oocytes.
AB  - In order to examine its effect on oocyte lipid content and cryosurvival,
      Forskolin was added to the medium for in vitro maturation of porcine oocytes.
      Treatments were control (IVM without Forskolin during the 42 h incubation
      period), addition of 10 MUM Forskolin for the entire 42 h (0-42) and addition of
      10 MUM Forskolin between 24 and 42 h only (24-42). In Experiment 1, treatments
      did not differ significantly in cleavage rate, but the blastocyst formation rate
      was lower in the 0-42 group than for control and 24-42 group oocytes (17, 32 and
      40%, respectively; P < 0.05). It was shown in Experiment 2 that Forskolin
      treatment from 0-42 h and from 24-42 h significantly reduced lipid content of
      oocytes compared to that of control cells (65 and 99 vs. 140 MUm(2) intensity of
      fluorescence, respectively; P < 0.05). In Experiment 3, the percentage of oocyte
      survival after cryopreservation and thawing was significantly higher in both
      Forskolin treatment groups than in control oocytes (72% for 0-42, 65% for 24-42
      and 52% for control; P < 0.05). However, Forskolin treatment did not increase
      cleavage rates of vitrified in vitro matured porcine oocytes (Control group 28%,
      0-42 h group 0%, 24-42 h group 26.67%). Addition of Forskolin affected the
      nuclear maturation of porcine oocytes. The percentage of PBE (polar body
      extrusion) were significantly reduced in the 0-42 h group (0-42 h group 42.00 +/-
      2.08 vs. Control group 79.70 +/- 2.82 and 24-42 h group 70.60 +/- 2.83; P <
      0.05). The 24-42 h group showed similar nuclear status to that of the Control
      group. We propose that delipation engendered by incubation with 10 MUM Forskolin
      during 24-42 hours of maturation increased cryosurvival of in vitro-maturated
      porcine oocytes and that attendant chemical lipolysis did not impair their
      further development as it may have done in oocytes incubated with Forskolin for
      the full 42 h.

PMID- 21187281
TI  - Use of NSAIDs for osteoarthritis amongst older-aged primary care patients:
      engagement with information and perceptions of risk.
AB  - BACKGROUND: non-steroidal anti-inflammatory drugs (NSAIDs) are used commonly to
      treat osteoarthritis in older patients. OBJECTIVE: to explore the understandings
      of risk that older-aged primary care patients have in the context of the use of
      oral NSAIDs to treat osteoarthritis. METHOD: semi-structured interviews were
      conducted with 15 patients who were recruited from four general practices located
      in Sydney, Australia. Patients were aged at least 65 years and were currently
      taking, or in the past 2 years had taken, an NSAID for osteoarthritis. Emergent
      themes were identified from the transcripts and were compared within and across
      transcripts to develop more abstract concepts. RESULTS: patients demonstrated
      three key 'modes of disengagement' from medication-specific risk information,
      each of which could also be a mode of modulating a sense of danger and each of
      which would demand a unique clinical response. These were: 'transference of
      responsibility'-transferring the responsibility to their GP, 'general versus
      specific risk'-considering the risk of taking medicine in general as opposed to
      the specific risk of taking an NSAID, and 'personal immunity'-some patients with
      a long history of NSAID use without apparent toxicity believed they were,
      therefore, not at risk of future adverse effects, while a few patients believed
      they were immune to adverse effects of drugs in general. CONCLUSION: there is a
      need for greater recognition of these 'modes of disengagement'/'hazard
      modulation' in order to attain a clinical response leading to safer, more
      effective and more ethical use of medicines.

PMID- 21187282
TI  - Allosteric modulation of the calcium-sensing receptor by gamma-glutamyl peptides:
      inhibition of PTH secretion, suppression of intracellular cAMP levels, and a
      common mechanism of action with L-amino acids.
AB  - gamma-Glutamyl peptides were identified previously as novel positive allosteric
      modulators of Ca(2+)(o)-dependent intracellular Ca(2+) mobilization in HEK-293
      cells that bind in the calcium-sensing receptor VFT domain. In the current study,
      we investigated whether gamma-glutamyl-tripeptides including gamma-Glu-Cys-Gly
      (glutathione) and its analogs S-methylglutathione and S-propylglutathione, or
      dipeptides including gamma-Glu-Ala and gamma-Glu-Cys are positive allosteric
      modulators of Ca(2+)(o)-dependent Ca(2+)(i) mobilization and PTH secretion from
      normal human parathyroid cells as well as Ca(2+)(o)-dependent suppression of
      intracellular cAMP levels in calcium-sensing receptor (CaR)-expressing HEK-293
      cells. In addition, we compared the effects of the potent gamma-glutamyl peptide
      S-methylglutathione, and the amino acid L-Phe on HEK-293 cells that stably
      expressed either the wild-type CaR or the double mutant T145A/S170T, which
      exhibits selectively impaired responses to L-amino acids. We find that gamma
      glutamyl peptides are potent positive allosteric modulators of the CaR that
      promote Ca(2+)(o)-dependent Ca(2+)(i) mobilization, suppress intracellular cAMP
      levels and inhibit PTH secretion from normal human parathyroid cells.
      Furthermore, we find that the double mutant T145A/S170T exhibits markedly
      impaired Ca(2+)(i) mobilization and cAMP suppression responses to S
      methylglutathione as well as L-Phe indicating that gamma-glutamyl peptides and L
      amino acids activate the CaR via a common mechanism.

PMID- 21187284
TI  - Angiomotin-like proteins associate with and negatively regulate YAP1.
AB  - In both Drosophila and mammalian systems, the Hippo pathway plays an important
      role in controlling organ size, mainly through its ability to regulate cell
      proliferation and apoptosis. The key component in the Hippo pathway is the Yes
      associated protein YAP1, which localizes in nucleus, functions as a
      transcriptional coactivator, and regulates the expression of several
      proliferation- and apoptosis-related genes. The Hippo pathway negatively
      regulates YAP1 transcriptional activity by modulating its nuclear-cytoplasmic
      localization in a phosphorylation-dependent manner. Here, we describe the
      identification of several new PY motif-containing proteins, including angiomotin
      like protein 1 (AMOTL1) and 2 (AMOTL2), as YAP1-associated proteins. We
      demonstrate that AMOTL1 and AMOTL2 can regulate YAP1 cytoplasm-to-nucleus
      translocation through direct protein-protein interaction, which can occur
      independent of YAP1 phosphorylation status. Moreover, down-regulation of AMOTL2
      in MCF10A cells promotes epithelial-mesenchymal transition, a phenotype that is
      also observed in MCF10A cells with YAP1 overexpression. Together, these data
      support a new mechanism for YAP1 regulation, which is mediated via its direct
      interactions with angiomotin-like proteins.

PMID- 21187283
TI  - Switch of PMCA4 splice variants in bovine epididymis results in altered isoform
      expression during functional sperm maturation.
AB  - Ca(2+) and Ca(2+)-dependent signals are essential for sperm maturation and
      fertilization. In mouse sperm the plasma membrane Ca(2+)-ATPase (PMCA) isoform 4
      plays a crucial role in Ca(2+) transport. The two major splice variants of PMCA4
      are PMCA4a and PMCA4b. PMCA4a differs from PMCA4b in the mechanism of calmodulin
      binding and activation. PMCA4a shows a much higher basal activity and is more
      effective than PMCA4b in returning Ca(2+) to resting levels. Knock-out mice
      carrying a PMCA4-null mutation are infertile because their sperm cannot achieve a
      hyperactivated state of motility. As sperm reach functional maturity during their
      transit through the epididymis, the expression of PMCA4a and 4b was assessed in
      bull testis and epididymis. Quantitative PCR revealed that PMCA4b is the major
      splice variant in testis, caput, and corpus epididymidis. In contrast, PMCA4a is
      the major splice variant in cauda epididymidis, whereas sperm are
      transcriptionally silent. Immunohistochemical staining using a new antibody
      against bovine PMCA4a located the PMCA4a to the apical membrane of the epithelium
      of cauda epididymidis, whereas testis, caput, and corpus epididymidis were
      negative. Western blotting of testis, epididymis, and sperm isolated from caput
      and cauda epididymidis showed a much higher level of PMCA4a in cauda epididymidis
      and sperm from cauda epididymidis compared with testis membranes and sperm from
      caput epididymidis. These findings suggest that PMCA4a is transferred to bovine
      sperm membranes in cauda epididymidis. This isoform switch may facilitate a
      higher calcium turnover in sperm necessary to traverse the female genital tract.

PMID- 21187285
TI  - Phospholipase Cdelta3 regulates RhoA/Rho kinase signaling and neurite outgrowth.
AB  - Phospholipase Cdelta3 (PLCdelta3) is a key enzyme regulating phosphoinositide
      metabolism; however, its physiological function remains unknown. Because
      PLCdelta3 is highly enriched in the cerebellum and cerebral cortex, we examined
      the role of PLCdelta3 in neuronal migration and outgrowth. PLCdelta3 knockdown
      (KD) inhibits neurite formation of cerebellar granule cells, and application of
      PLCdelta3KD using in utero electroporation in the developing brain results in the
      retardation of the radial migration of neurons in the cerebral cortex. In
      addition, PLCdelta3KD inhibits axon and dendrite outgrowth in primary cortical
      neurons. PLCdelta3KD also suppresses neurite formation of Neuro2a neuroblastoma
      cells induced by serum withdrawal or treatment with retinoic acid. This
      inhibition is released by the reintroduction of wild-type PLCdelta3.
      Interestingly, the H393A mutant lacking phosphatidylinositol 4,5-bisphosphate
      hydrolyzing activity generates supernumerary protrusions, and a constitutively
      active mutant promotes extensive neurite outgrowth, indicating that PLC activity
      is important for normal neurite outgrowth. The introduction of dominant negative
      RhoA (RhoA-DN) or treatment with Y-27632, a Rho kinase-specific inhibitor,
      rescues the neurite extension in PLCdelta3KD Neuro2a cells. Similar effects were
      also detected in primary cortical neurons. Furthermore, the RhoA expression level
      was significantly decreased by serum withdrawal or retinoic acid in control
      cells, although this decrease was not observed in PLCdelta3KD cells. We also
      found that exogenous expression of PLCdelta3 down-regulated RhoA protein, and
      constitutively active PLCdelta3 promotes the RhoA down-regulation more
      significantly than PLCdelta3 upon differentiation. These results indicate that
      PLCdelta3 negatively regulates RhoA expression, inhibits RhoA/Rho kinase
      signaling, and thereby promotes neurite extension.

PMID- 21187287
TI  - Sugar binding residue affects apparent Na+ affinity and transport stoichiometry
      in mouse sodium/glucose cotransporter type 3B.
AB  - SGLT1 is a sodium/glucose cotransporter that moves two Na(+) ions with each
      glucose molecule per cycle. SGLT3 proteins belong to the same family and are
      described as glucose sensors rather than glucose transporters. Thus, human SGLT3
      (hSGLT3) does not transport sugar, but extracellular glucose depolarizes the cell
      in which it is expressed. Mouse SGLT3b (mSGLT3b), although it transports sugar,
      has low apparent sugar affinity and partially uncoupled stoichiometry compared
      with SGLT1, suggesting that mSGLT3b is also a sugar sensor. The crystal structure
      of the Vibrio parahaemolyticus SGLT showed that residue Gln(428) interacts
      directly with the sugar. The corresponding amino acid in mammalian proteins, 457,
      is conserved in all SGLT1 proteins as glutamine. In SGLT3 proteins, glutamate is
      the most common residue at this position, although it is a glycine in mSGLT3b and
      a serine in rat SGLT3b. To test the contribution of this residue to the function
      of SGLT3 proteins, we constructed SGLT3b mutants that recapitulate residue 457 in
      SGLT1 and hSGLT3, glutamine and glutamate, respectively. The presence of
      glutamine at residue 457 increased the apparent Na(+) and sugar affinities,
      whereas glutamate decreased the apparent Na(+) affinity. Moreover, glutamate
      transported more cations per sugar molecule than the wild type protein. We
      propose a model where cations are released intracellularly without the release of
      sugar from an intermediate state. This model explains the uncoupled charge:sugar
      transport phenotype observed in wild type and G457E-mSGLT3b compared with SGLT1
      and the sugar-activated cation transport without sugar transport that occurs in
      hSGLT3.

PMID- 21187286
TI  - Cellular up-regulation of Nedd4 family interacting protein 1 (Ndfip1) using low
      levels of bioactive cobalt complexes.
AB  - The delivery of metal ions using cell membrane-permeable metal complexes
      represents a method for activating cellular pathways. Here, we report the
      synthesis and characterization of new [Co(III)(salen)(acac)] complexes capable of
      up-regulating the ubiquitin ligase adaptor protein Ndfip1. Ndfip1 is a
      neuroprotective protein that is up-regulated in the brain after injury and
      functions in combination with Nedd4 ligases to ubiquitinate harmful proteins for
      removal. We previously showed that Ndfip1 can be increased in human neurons using
      CoCl(2) that is toxic at high concentration. Here we demonstrate a similar effect
      can be achieved by low concentrations of synthetic Co(III) complexes that are non
      toxic and designed to be activated following cellular entry. Activation is
      achieved by intracellular reduction of Co(III) to Co(II) leading to release of
      Co(II) ions for Ndfip1 up-regulation. The cellular benefit of Ndfip1 up
      regulation by Co(III) complexes includes demonstrable protection against cell
      death in SH-SY5Y cells during stress. In vivo, focal delivery of Co(III)
      complexes into the adult mouse brain was observed to up-regulate Ndfip1 in
      neurons. These results demonstrate that a cellular response pathway can be
      advantageously manipulated by chemical modification of metal complexes, and
      represents a significant step of harnessing low concentration metal complexes for
      therapeutic benefit.

PMID- 21187288
TI  - Molecular control of polyene macrolide biosynthesis: direct binding of the
      regulator PimM to eight promoters of pimaricin genes and identification of
      binding boxes.
AB  - Control of polyene macrolide production in Streptomyces natalensis is mediated by
      the transcriptional activator PimM. This regulator, which combines an N-terminal
      PAS domain with a C-terminal helix-turn-helix motif, is highly conserved among
      polyene biosynthetic gene clusters. PimM, truncated forms of the protein without
      the PAS domain (PimM(DeltaPAS)), and forms containing just the DNA-binding domain
      (DBD) (PimM(DBD)) were overexpressed in Escherichia coli as GST-fused proteins.
      GST-PimM binds directly to eight promoters of the pimaricin cluster, as
      demonstrated by electrophoretic mobility shift assays. Assays with truncated
      forms of the protein revealed that the PAS domain does not mediate specificity or
      the distinct recognition of target genes, which rely on the DBD domain, but
      significantly reduces binding affinity up to 500-fold. Transcription start points
      were identified by 5'-rapid amplification of cDNA ends, and the binding regions
      of PimM(DBD) were investigated by DNase I protection studies. In all cases,
      binding took place covering the -35 hexamer box of each promoter, suggesting an
      interaction of PimM and RNA polymerase to cause transcription activation.
      Information content analysis of the 16 sequences protected in target promoters
      was used to deduce the structure of the PimM-binding site. This site displays
      dyad symmetry, spans 14 nucleotides, and adjusts to the consensus TVGGGAWWTCCCBA.
      Experimental validation of this binding site was performed by using synthetic DNA
      duplexes. Binding of PimM to the promoter region of one of the polyketide
      synthase genes from the Streptomyces nodosus amphotericin cluster containing the
      consensus binding site was also observed, thus proving the applicability of the
      findings reported here to other antifungal polyketides.

PMID- 21187290
TI  - Role of palliative tracheobronchial stenting in hospice patients: boon or bane?
AB  - Lung cancer is the leading cause of cancer mortality and morbidity. Patients with
      advanced lung cancer have distressful symptoms like dyspnea. It has severe
      negative impact on the quality of life. Airway stenting has become widespread for
      palliation of airway stenosis in patients with metastatic airways disease.
      Although it provides improvement in symptoms, actual survival benefit is limited
      with severe potential complications. Appropriate patient selection in terms of
      site of tumor, type of stent placement is needed to achieve maximum benefit for
      patients. Here we will discuss 2 patients with advanced lung cancer who received
      bronchial stent for intractable dyspnea. Although there was dramatic improvement
      in symptoms and quality of life, both died shortly. Was there any benefit of
      stenting remained unanswered.

PMID- 21187289
TI  - Structure-function analysis of VPS9-ankyrin-repeat protein (Varp) in the
      trafficking of tyrosinase-related protein 1 in melanocytes.
AB  - Because Varp (VPS9-ankyrin-repeat protein)/Ankrd27 specifically binds two small
      GTPases, Rab32 and Rab38, which redundantly regulate the trafficking of
      melanogenic enzymes in mammalian epidermal melanocytes, it has recently been
      implicated in the regulation of trafficking of a melanogenic enzyme tyrosinase
      related protein 1 (Tyrp1) to melanosomes. However, the functional interaction
      between Rab32/38 and Varp and the involvement of the VPS9 domain (i.e. Rab21-GEF
      domain) in Tyrp1 trafficking have never been elucidated. In this study, we
      succeeded in identifying critical residues of Rab32/38 and Varp that are critical
      for the formation of the Rab32/38.Varp complex by performing Ala-based site
      directed mutagenesis, and we discovered that a conserved Val residue in the
      switch II region of Rab32(Val-92) and Rab38(Val-78) is required for Varp binding
      activity and that its point mutant, Rab38(V78A), does not support Tyrp1
      trafficking in Rab32/38-deficient melanocytes. We also identified two critical
      residues for Rab32/38 binding in the Varp ANKR1 domain and demonstrated that
      their point mutants, Varp(Q509A) and Varp(Y550A), do not support peripheral
      melanosomal distribution of Tyrp1 in Varp-deficient cells. Interestingly, the
      VPS9 domain point mutants, Varp(D310A) and Varp(Y350A), did support Tyrp1
      trafficking in Varp-deficient cells, and knockdown of Rab21 had no effect on
      Tyrp1 distribution. We also found evidence for the functional interaction between
      a vesicle SNARE VAMP7/TI-VAMP and Varp in Tyrp1 trafficking. These results
      collectively indicated that both the Rab32/38 binding activity and VAMP7 binding
      activity of Varp are essential for trafficking of Tyrp1 in melanocytes but that
      activation of Rab21 by the VPS9 domain is not necessary for Tyrp1 trafficking.

PMID- 21187291
TI  - Review article: palliative care in gynecologic oncology.
AB  - Patients with advanced gynecologic malignancies have a multitude of symptoms;
      pain, nausea, and vomiting, constipation, anorexia, diarrhea, dyspnea, as well as
      symptoms resulting from intestinal obstruction, hypercalcemia, ascites, and/or
      ureteral obstruction. Pain is best addressed through a multimodal approach. The
      optimum palliative management of end-stage malignant intestinal obstruction
      remains controversial, with no clear guidelines governing the choice of surgical
      versus medical management. Patient selection for palliative surgery, therefore,
      should be highly individualized because only carefully selected candidates may
      derive real benefit from such surgeries. There remains a real need for more
      emphasis on palliative care education in training programs.

PMID- 21187292
TI  - Strenuous endurance exercise: is more better for everyone? Our genes won't tell
      us.

PMID- 21187293
TI  - Assessment of synovitis with contrast-enhanced MRI using a whole-joint
      semiquantitative scoring system in people with, or at high risk of, knee
      osteoarthritis: the MOST study.
AB  - OBJECTIVES: To introduce a comprehensive and reliable scoring system for the
      assessment of whole-knee joint synovitis based on contrast-enhanced (CE) MRI.
      METHODS: Multicenter Osteoarthritis Study (MOST) is a cohort study of people
      with, or at high risk of, knee osteoarthritis (OA). Subjects are an unselected
      subset of MOST who volunteered for CE-MRI. Synovitis was assessed at 11 sites of
      the joint. Synovial thickness was scored semiquantitatively: grade 0 (<2 mm),
      grade 1 (2-4 mm) and grade 2 (>4 mm) at each site. Two musculoskeletal
      radiologists performed the readings and inter- and intrareader reliability was
      evaluated. Whole-knee synovitis was assessed by summing the scores from all
      sites. The association of Western Ontario and McMaster Osteoarthritis Index pain
      score with this summed score and with the maximum synovitis grade for each site
      was assessed. RESULTS: 400 subjects were included (mean age 58.8+/-7.0 years,
      body mass index 29.5+/-4.9 kg/m(2), 46% women). For individual sites, intrareader
      reliability (weighted kappa) was 0.67-1.00 for reader 1 and 0.60-1.00 for reader
      2. Inter-reader agreement (kappa) was 0.67-0.92. For the summed synovitis scores,
      intrareader reliability (intraclass correlation coefficient ( ICC)) was 0.98 and
      0.96 for each reader and inter-reader agreement (ICC) was 0.94. Moderate to
      severe synovitis in the parapatellar subregion was associated with the higher
      maximum pain score (adjusted OR (95% CI), 2.8 (1.4 to 5.4) and 3.1 (1.2 to 7.9),
      respectively). CONCLUSIONS: A comprehensive semiquantitative scoring system for
      the assessment of whole-knee synovitis is proposed. It is reliable and identifies
      knees with pain, and thus is a potentially powerful tool for synovitis assessment
      in epidemiological OA studies.

PMID- 21187294
TI  - Expansion of myelin autoreactive CD8+ T lymphocytes in patients with
      neuropsychiatric systemic lupus erythematosus.
AB  - OBJECTIVES: Delineation of mechanisms underlying neuropsychiatric systemic lupus
      erythematosus (NPSLE) and determination of biological markers could guide
      treatment choice. A study was undertaken to analyse the potential role of
      activated CD8+ T cells in NPSLE as previously reported in SLE nephritis. METHODS:
      Flow cytometric immunophenotyping of blood lymphocytes was performed in 30
      patients with NPSLE and 36 healthy individuals. The antigenic specificity of CD8+
      T cells was studied using HLA-A0201 tetramers loaded with several myelin-derived
      peptides. The intracellular level of interferon gamma (IFNgamma) produced by
      activated CD8+ T cells was determined by flow cytometry. RESULTS: A large
      increase in circulating activated CD8+ T lymphocytes expressing surface HLA-DR
      was found in patients with NPSLE without antiphospholipid syndrome (APS) (n=18)
      compared with patients with APS (n=12) or healthy controls (n=36). IFNgamma
      secreting myelin-specific CD8+ T cells were detected exclusively in the blood of
      patients with NPSLE without APS but with white matter lesions. CONCLUSIONS: These
      data strongly support the existence of a new immune effector mechanism
      responsible for CNS involvement in patients with NPSLE and suggest that analysing
      HLA-DR expression combined with myelin-specific tetramer staining on CD8+ T
      lymphocytes may be a valuable additional tool for the monitoring of these
      patients.

PMID- 21187295
TI  - Raloxifene for prevention of glucocorticoid-induced bone loss: a 12-month
      randomised double-blinded placebo-controlled trial.
AB  - OBJECTIVES: To study the efficacy of raloxifene in preventing bone mineral
      density (BMD) loss in women receiving long-term glucocorticoids (GC). The study
      took the form of a parallel-group randomised double-blinded placebo-controlled
      trial. METHODS: Postmenopausal women without hypercoagulability risk factors who
      were prevalent GC users were randomised to receive either raloxifene (60 mg/day)
      or placebo (1 tablet/day) on top of calcium (1000 mg/day) and calcitriol (0.25
      MUg/day). BMD of the hip and spine (primary outcome), bone turnover markers and
      new vertebral fractures (secondary outcomes) at month 12 were assessed. RESULTS:
      Between December 2006 and December 2008, 114 patients were recruited (age 55.3+/
      7.7 years). The duration and dose of prednisolone received was 62.2+/-64 months
      and 6.7+/-5.9 mg/day, respectively. Baseline vertebral fracture was present in
      six (5%) patients. In all, 57 patients were allocated to each of the treatment
      arms. Demographic data, osteoporotic risk factors and BMD at various sites were
      similar between the two groups of patients. At month 12, a significant gain in
      the lumbar spine (+1.3+/-0.4%; p=0.004) and total hip BMD (+1.0+/-0.4%; p=0.01)
      was observed in patients treated with raloxifene but a significant decrease in
      BMD of the lumbar spine (-0.9+/-0.4%; p=0.045) and hip (-0.8+/-0.3%; p=0.01)
      occurred in the placebo group. The femoral neck BMD did not change significantly
      in favour of raloxifene. Three new fractures developed exclusively in the
      patients treated with placebo. Bone formation (serum osteocalcin and procollagen
      type I N-terminal) and resorption (urine deoxypyridinoline and type I collagen)
      markers decreased significantly in the raloxifene group but not in patients
      treated with placebo. Leg cramps were numerically more frequent in the raloxifene
      group (7% vs 0%) but thromboembolism was not reported in any patients.
      CONCLUSIONS: In postmenopausal women receiving long-term GCs, raloxifene is well
      tolerated and significantly increases spinal and hip BMD after 12 months of
      treatment.

PMID- 21187296
TI  - A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with
      systemic sclerosis in a large European cohort.
AB  - OBJECTIVES: The aim of this study was to confirm the influence of TNFSF4
      polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features.
      METHODS: A total of 8 European populations of Caucasian ancestry were included,
      comprising 3014 patients with SSc and 3125 healthy controls. Four genetic
      variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904)
      were selected as genetic markers. RESULTS: A pooled analysis revealed the
      association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI
      1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant
      association of the four tested variants with patients with limited cutaneous SSc
      (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91,
      95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR
      1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904
      minor alleles with patients positive for anti-centromere antibodies (ACA)
      remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25;
      OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a
      protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR
      0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to
      0.97, respectively) and revealed a new risk haplotype associated with the same
      groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35;
      OR 1.23, 95% CI 1.07 to 1.42, respectively). CONCLUSIONS: The data confirm the
      influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in
      subsets of patients positive for lcSSc and ACA.

PMID- 21187297
TI  - Tumour necrosis factor alpha-driven IL-32 expression in rheumatoid arthritis
      synovial tissue amplifies an inflammatory cascade.
AB  - OBJECTIVE: To investigate the interplay between IL-32 and tumour necrosis factor
      alpha (TNFalpha) during the chronic inflammation of rheumatoid arthritis (RA) and
      to assess whether anti-TNFalpha treatment of RA patients modulates synovial IL-32
      expression. METHODS: Induction of IL-32gamma by Pam3Cys, lipopolysaccharide, IL
      1beta or TNFalpha was investigated in human fibroblast-like synoviocytes (FLS).
      Stimulation of TNFalpha production by IL-32gamma was studied by adenoviral
      overexpression of IL-32gamma (AdIL-32gamma) and lipopolysaccharide stimulation of
      THP1 cells. Silencing of endogenous IL-32 was employed to study cytokine
      regulation in FLS. AdIL-32gamma followed by TNFalpha stimulation was performed in
      FLS to investigate cytokine induction. Immunohistochemistry was applied to study
      IL-32 expression in synovial biopsies from RA patients. RESULTS: TNFalpha
      potently induced IL-32gamma expression in FLS. Increased TNFalpha, IL-1beta, IL-6
      and CXCL8 production was observed after IL-32gamma overexpression and
      lipopolysaccharide stimulation of THP1 cells. TNFalpha stimulation of FLS after
      silencing IL-32gamma resulted in diminished IL-6 and CXCL8 production, whereas IL
      32gamma overexpression resulted in enhanced IL-6 and CXCL8 levels. Remarkably,
      the mechanism through which IL-32gamma overexpression induced TNFalpha, IL-1beta
      and CXCL8 was by counteracting messenger RNA decay. Importantly, treatment of RA
      patients with anti-TNFalpha resulted in significant reduction of IL-32 protein in
      synovial tissue. CONCLUSIONS: TNFalpha is a potent inducer of endogenous IL-32
      expression and IL-32 itself contributes to prolonged TNFalpha production, thus
      inducing an important auto-inflammatory loop. Treatment of RA patients with anti
      TNFalpha antibodies diminished IL-32 expression in synovial tissue. The potent
      anti-inflammatory effect of TNFalpha blockade in RA patients may be partly due to
      the reduction of synovial IL-32 expression.

PMID- 21187298
TI  - Effectiveness and safety of the interleukin 6-receptor antagonist tocilizumab
      after 4 and 24 weeks in patients with active rheumatoid arthritis: the first
      phase IIIb real-life study (TAMARA).
AB  - OBJECTIVES: To confirm the effectiveness and safety of the interleukin 6-receptor
      antagonist tocilizumab in patients with rheumatoid arthritis (RA) in a setting
      close to real-life medical care in Germany. METHODS: A multicentre open-label
      phase IIIb study was undertaken. Patients with active RA with a 28-joint Disease
      Activity Score (DAS28) >3.2 despite previous disease-modifying antirheumatic
      drugs (DMARDs) were treated with tocilizumab 8 mg/kg every 4 weeks. The primary
      end point was the proportion of patients achieving LDAS <=3.2 at week 24;
      secondary end points included American College of Rheumatology (ACR), European
      League Against Rheumatism (EULAR) or Clinical Disease Activity Index (CDAI)
      responses and decrease in acute phase. Analyses in subgroups such as rheumatoid
      factor (RF)-positive versus RF-negative patients and patients with an inadequate
      response to treatment with DMARDs (DMARD-IR) versus those with an inadequate
      response to tumour necrosis factor (TNF) antagonists (TNF antagonist-IR) were
      performed. Safety was assessed by adverse event documentation. RESULTS: 286
      patients were treated and 83.6% completed the study. 41.6% had previously been
      treated with TNF antagonists. 57% of the intention-to-treat patients achieved the
      primary end point of LDAS, 47.6% achieved DAS remission <2.6 and a EULAR 'good
      response' was achieved by 54.9%; ACR50/70 response rates at week 24 were 50.7%
      and 33.9%, respectively. The mean+/-SD decrease in CDAI from baseline to week 24
      was 71+/-29%. C reactive protein levels normalised rapidly within 1 week. Major
      improvements in fatigue, pain and morning stiffness were observed in the first 4
      weeks and further improved until week 24. DAS28, EULAR and ACR responses at week
      24 did not differ between RF-positive and RF-negative patients. TNF antagonist
      naive patients responded better than patients who had previously failed on TNF
      antagonists. The safety profile of tocilizumab was comparable to that previously
      observed in the phase III trial programme. Serious infections were observed in
      3.1% of patients. CONCLUSIONS: Tocilizumab is highly effective in a setting close
      to real-life medical care with a rapid and sustained improvement in signs and
      symptoms of RA. A manageable safety profile was seen over the 24-week study
      period.

PMID- 21187299
TI  - No-show at a forensic psychiatric outpatient clinic: risk factors and reasons.
AB  - Nonattendance for and late cancellations of scheduled appointments, that is no
      show, is a well-known phenomenon in psychiatric outpatient clinics. Research on
      the topic of no-show for initial and consecutive appointments in the field of
      forensic psychiatry is scarce. This study therefore aims to determine the
      prevalence and causes of no-show and to explore reasons for nonattendance. The
      study was carried out in an outpatient clinic in northern Netherlands. Telephone
      interviews were administered to 27 no-show clients, 84 follow-up no-show clients,
      and 41 attendees of 18 years and older. A no-show rate of 24.9% and a follow-up
      no-show rate of 9.8% was found. The majority of appointments missed were in the
      beginning phase of clinic contact. No-show clients were younger than their
      attending counterparts and more often dropped out from clinic contact. Also, less
      family social support was experienced by nonattendees. Reasons for nonattendance
      were having forgotten about appointment and work commitments.

PMID- 21187300
TI  - The effects of self-control, gang membership, and parental
      attachment/identification on police contacts among Latino and African American
      youths.
AB  - This study assessed the correlates of self-control and police contact in a sample
      of Chicago public high school students. The investigation examined the effects of
      parental attachment/identification, family structure, and peer association on
      self-control and the effects of parental attachment/identification, family
      structure, peer association, and self-control on police contact. Differences
      between African American and Latino youth on the predictors of the two dependent
      measures were tested in separate regression models. Weak parental
      attachment/identification and gang affiliation (peer association) predicted low
      self-control among all students. Among African American youth, only weak maternal
      attachment/identification predicted low self-control; both weak maternal
      attachment/identification and gang affiliation predicted low self-control among
      Latino youth. Gang affiliation predicted police stops (delinquency) among African
      Americans but not among Latinos. However, both African American and Latino
      students with lower self-control were more likely to be stopped by the police
      than those with higher self-control.

PMID- 21187301
TI  - Comparing recidivism rates of treatment responders/nonresponders in a sample of
      413 child molesters who had completed community-based sex offender treatment in
      the United kingdom.
AB  - Analysis of psychometric data from a sample of 413 child molesters who had
      completed a U.K. probation-based sex offender treatment program was carried out
      to assess (a) the effectiveness of therapy in the short term and (b) the longer
      term implications of treatment in relation to sexual recidivism. It was found
      that 12% (51 offenders) of the sample had recidivated within 2 to 4 years. Of
      these recidivists, 86% (44 offenders) had been reconvicted for a sexually related
      offense. One hundred thirty-five offenders (33%) demonstrated a treated profile
      (i.e., demonstrated no offense-specific problems and few, or no, socioaffective
      problems at the posttreatment stage). This group was compared with a sample of
      offenders deemed as not responding to treatment, matched by their levels of
      pretreatment risk/need. It was found that a significantly smaller proportion (n =
      12, 9%) of treatment responders had recidivated, compared to the treatment
      nonresponders (n = 20, 15%), indicating a 40% reduction in recidivism in those
      who had responded to treatment (effect size = .18). Matching length of treatment
      to the offenders' level of pretreatment risk/need (i.e., higher risk/treatment
      need offenders typically undertook longer treatment) reduced the rate of
      recidivism among this group to the level of recidivism observed among the lower
      risk/need offenders.

PMID- 21187302
TI  - Analysis of the stages of change model of drug and alcohol treatment readiness
      among prisoners.
AB  - A classification and regression tree (CART) analysis was applied to data for 237
      male participants (M = 31.93 years, SD = 7.64) in a prison-based substance abuse
      treatment program to study the integrity of the Stages of Change model of
      treatment readiness. Using the Stages of Change Questionnaire (STOCQ),
      participants were assigned to Contemplation (102), Action (118), or Maintenance
      (17) groups. A CART analysis then examined differences in the overall group
      profiles on the basis of scores on the Psychological Inventory of Criminal
      Thinking, the Situational Confidence Questionnaire, and the Carlson Psychological
      Survey. The assumption of discrete stages of change was not supported.
      Alternative models are suggested: one based on states of change and one on
      personality characteristics. A focus on equal attention to both cognitive and
      behavioral aspects of substance abuse treatment readiness is suggested.

PMID- 21187304
TI  - Clinical report-health supervision for children with Prader-Willi syndrome.
AB  - This set of guidelines was designed to assist the pediatrician in caring for
      children with Prader-Willi syndrome diagnosed by clinical features and confirmed
      by molecular testing. Prader-Willi syndrome provides an excellent example of how
      early diagnosis and management can improve the long-term outcome for some genetic
      disorders.

PMID- 21187303
TI  - Differential growth patterns among healthy infants fed protein hydrolysate or cow
      milk formulas.
AB  - OBJECTIVE: Infant formulas differ considerably in composition and sensory
      profiles. In this randomized study, we examined whether healthy infants fed an
      extensively protein hydrolysate formula (PHF) would differ in feeding behavior
      and growth from those fed cow-milk formula (CMF). PATIENTS AND METHODS: Infants
      were randomly assigned to be fed CMF or PHF between 0.5 and 7.5 months of age.
      Each month for 7 months, infants were weighed and measured and then videotaped
      while being fed their assigned formula. Anthropometric z scores were calculated
      by using World Health Organization growth standards. Multilevel linear growth and
      piecewise mixed-effects models compared trajectories for growth measures and
      formula acceptance. RESULTS: When compared with infants fed CMF, infants fed PHF
      had significantly lower weight-for-length z scores across ages 2.5 to 7.5 months.
      There were no differences in length-for-age z scores, which indicate that group
      differences resulted from gains in weight, not length. Infants fed PHF also had
      significantly slower weight gain velocity compared with infants fed CMF. During
      the monthly assessments, PHF-fed infants consumed less formula to satiation than
      did CMF-fed infants across the study period. Maternal ratings of infants'
      acceptance of the formula did not differ at any age. CONCLUSIONS: z-score
      trajectories indicate that CMF-fed infants' weight gain was accelerated, whereas
      PHF-fed infants' weight gain was normative. Whether such differences in growth
      are because of differences in the protein content or amino acid profile of the
      formulas and, in turn, metabolism is unknown. Research on the long-term
      consequences of these early growth differences is needed.

PMID- 21187305
TI  - Multicenter crossover study of automated control of inspired oxygen in ventilated
      preterm infants.
AB  - OBJECTIVE: To determine the efficacy and safety of automated adjustment of the
      fraction of inspired oxygen (Fio(2)) adjustment in maintaining arterial oxygen
      saturation (Spo(2)) within an intended range for mechanically ventilated preterm
      infants with frequent episodes of decreased Spo(2). METHODS: Thirty-two infants
      (gestational age [median and interquartile range]: 25 weeks [24-27 weeks]; age:
      27 days [17-36 days]) were studied during 2 consecutive 24-hour periods, one with
      Fio(2) adjusted by clinical staff members (manual) and the other by an automated
      system (automated), in random sequence. RESULTS: Time with Spo(2) within the
      intended range (87%-93%) increased significantly during the automated period,
      compared with the manual period (40% +/- 14% vs 32% +/- 13% [mean +/- SD]). Times
      with Spo(2) of >93% or >98% were significantly reduced during the automated
      period (21% +/- 20% vs 37% +/- 12% and 0.7% vs 5.6% [interquartile ranges: 0.1%
      7.2% and 2.7%-11.2%], respectively). Time with Spo(2) of <87% increased
      significantly during the automated period (32% +/- 12% vs 23% +/- 9%), with more
      frequent episodes with Spo(2) between 80% and 86%, whereas times with Spo(2) of
      <80% or <75% did not differ between periods. Hourly median Fio(2) values
      throughout the automated period were lower and there were substantially fewer
      manual Fio(2) changes (10 +/- 9 vs 112 +/- 59 changes per 24 hours; P < .001),
      compared with the manual period. CONCLUSIONS: In infants with fluctuations in
      Spo(2), automated Fio(2) adjustment improved maintenance of the intended Spo(2)
      range led to reduced time with high Spo(2) and more-frequent episodes with Spo(2)
      between 80% and 86%.

PMID- 21187306
TI  - Prevalence of noise-induced hearing-threshold shifts and hearing loss among US
      youths.
AB  - OBJECTIVE: We investigated trends in noise-induced threshold shifts (NITSs), high
      frequency hearing loss (HFHL), and low-frequency hearing loss (LFHL). METHODS: A
      total of 4310 adolescents 12 to 19 years of age completed audiometric testing
      during National Health and Nutrition Examination Surveys in 1988-1994 and 2005
      2006. NITS criteria were audiometric patterns of decreased 3- to 6-kHz thresholds
      but preserved 0.5- to 1-kHz and 8-kHz thresholds; HFHL and LFHL criteria were
      high and low pure-tone averages, respectively, of >15 dB HL. RESULTS: There were
      no significant increases in NITSs (odds ratio [OR]: 0.81 [95% confidence interval
      [CI]: 0.53-1.22]; P = .29), HFHL (OR: 1.21 [95% CI: 0.87-1.69]; P = .25), or LFHL
      (OR: 1.37 [95% CI: 0.77-2.45]; P = .28) between survey periods. However, a
      significant increase in the prevalence of NITSs occurred among female youths
      (11.6% [95% CI: 9.0%-14.1%] vs 16.7% [95% CI: 13.2%-20.3%]; P < .0001). The
      overall prevalence of exposure to loud noise or listening to music through
      headphones in the previous 24 hours increased from 19.8% (95% CI: 17.6%-22.1%) to
      34.8% (95% CI: 31.0%-38.5%; P < .0001). In 2005-2006, female youths had a similar
      prevalence of exposure to recreational noise (23.6% [95% CI: 19.6%-27.6%] vs
      27.7% [95% CI: 23.6%-31.8%]; P < .0001) and a lower prevalence of hearing
      protection use (3.4% [95% CI: 1.6%-5.3%] vs 10.3% [95% CI: 7.3%-13.2%]; P <
      .0001) compared with male youths. CONCLUSIONS: Increased exposure to recreational
      noise and minimal use of hearing protection might have lead to an increase in
      NITS prevalence among female youths.

PMID- 21187308
TI  - Integrative pediatric care: parents' attitudes toward communication of physicians
      and CAM practitioners.
AB  - OBJECTIVE: In this study, we explored parents' perspectives toward complementary
      and alternative medicine (CAM) use by their children and its impact on parent
      doctor and doctor-CAM-practitioner communication. PATIENTS AND METHODS: We
      designed a 2-arm study of parents who approached either conventional primary care
      or CAM clinics with their children to consult physicians or practitioners
      regarding their child's health. RESULTS: A total of 599 parents responded to our
      questionnaire (319 in 5 conventional clinics [83.9% response rate] and 280 in 21
      CAM clinics [71.2% response rate]). Parents in conventional clinics reported less
      use of CAM by their children within the previous year (35.3% vs 73.7%; P < .0001)
      but used more traditional and homemade remedies (46.4% vs 12.7%; P < .0001). Both
      parent groups largely supported informing their child's physician regarding CAM
      use and expected the physician to initiate a CAM-related conversation and to
      refer their child to a CAM practitioner. The 2 groups' respondents largely
      supported communication between the child's physician and the CAM practitioner by
      the use of a referral/medical letter. Compared with respondents in CAM clinics,
      parents in conventional clinics were more supportive of CAM integration in a
      pediatric primary care setting and envisioned a more dominant role of physicians
      regarding CAM referral and a significant role of physicians in providing CAM.
      CONCLUSIONS: Parents who are referred to conventional and CAM clinics express
      distinctive attitudes toward CAM integration in pediatric care. Parents perceive
      physician-CAM practitioner communication as highly important and instrumental in
      promoting their children's health and safety.

PMID- 21187307
TI  - Serum dioxins and polychlorinated biphenyls are associated with growth among
      Russian boys.
AB  - OBJECTIVE: We evaluated the associations of serum dioxins and polychlorinated
      biphenyls (PCBs) with longitudinally assessed growth measurements among
      peripubertal Russian boys. METHODS: A total of 499 boys from Chapaevsk, Russia,
      aged 8 to 9 years were enrolled in the study from 2003 to 2005 and were followed
      prospectively for 3 years. Blood samples were collected and physical examinations
      were conducted at entry and repeated at annual study visits. Multivariate mixed
      effects regression models for repeated measures were used to examine the
      associations of serum dioxins and PCBs with longitudinal measurements of BMI,
      height, and height velocity. RESULTS: Serum dioxin (total 2005 toxic equivalency
      [TEQ] median: 21.1 pg/g lipid) and PCBs (median sum of PCBs: 250 ng/g lipid) were
      measured in 468 boys. At study entry and during 3 years of follow-up, >50% of the
      boys had age-adjusted BMI and height z scores within 1 SD of World Health
      Organization-standardized mean values for age. Boys in the highest exposure
      quintile of the sum of dioxin and PCB concentrations and total TEQs had a
      significant decrease in mean BMI z scores of 0.67 for dioxins and TEQs and 1.04
      for PCBs, compared with boys in the lowest exposure quintile. Comparison of the
      highest versus the lowest quintile revealed that higher serum PCB concentrations
      were associated with significantly lower height z scores (mean z-score decrease:
      0.41) and height velocity (mean decrease: 0.19 cm/year) after 3 years of follow
      up. CONCLUSIONS: Our findings suggest that exposures to dioxins and PCBs are
      associated with reduced growth during the peripubertal period and may compromise
      adult body mass, stature, and health.

PMID- 21187309
TI  - Clinical prediction rule for RSV bronchiolitis in healthy newborns: prognostic
      birth cohort study.
AB  - OBJECTIVE: Our goal was to determine predictors of respiratory syncytial virus
      (RSV) lower respiratory tract infection (LRTI) among healthy newborns. METHODS:
      In this prospective birth cohort study, 298 healthy term newborns born in 2 large
      hospitals in the Netherlands were monitored throughout the first year of life.
      Parents kept daily logs and collected nose/throat swabs during respiratory tract
      infections. The primary outcome was RSV LRTI, which was defined on the basis of
      the combination of positive RSV polymerase chain reaction results and acute
      wheeze or moderate/severe cough. RESULTS: Of the 298 children, 42 (14%) developed
      RSV LRTI. Independent predictors for RSV LRTI were day care attendance and/or
      siblings, high parental education level, birth weight of >4 kg, and birth in
      April to September. The area under the receiver operating characteristic curve
      was 0.72 (95% confidence interval: 0.64-0.80). We derived a clinical prediction
      rule; possible scores ranged from 0 to 5 points. The absolute risk of RSV LRTI
      was 3% for children with scores of <=2 (20% of all children) and 32% for children
      with all 4 factors (scores of 5; 8% of all children). Furthermore, 62% of the
      children with RSV LRTI experienced wheezing during the first year of life,
      compared with 36% of the children without RSV LRTI. CONCLUSIONS: A simple
      clinical prediction rule identifies healthy newborns at risk of RSV LRTI.
      Physicians can differentiate between children with high and low risks of RSV LRTI
      and subsequently can target preventive and monitoring strategies toward children
      at high risk.

PMID- 21187310
TI  - Intrauterine effects of maternal prepregnancy overweight on child cognition and
      behavior in 2 cohorts.
AB  - OBJECTIVE: Greater maternal prepregnancy adiposity has been associated with
      behavioral problems, such as attention-deficit/hyperactivity disorder, and lower
      intellectual function in offspring. However, few studies of humans have explored
      this, and it is unclear if intrauterine mechanisms or confounding factors drive
      these associations. PATIENTS AND METHODS: Parental adiposity and offspring verbal
      skills, nonverbal skills, and behavioral problems were assessed in the British
      Avon Longitudinal Study of Parents and Children (N = ~5000) and Dutch Generation
      R (N = ~2500) cohorts. We aimed to determine the plausibility of intrauterine
      effects by (1) adjusting for multiple confounders, (2) comparing associations
      between maternal and paternal overweight with offspring cognition/behaviors, and
      (3) searching for cross-cohort consistency. RESULTS: Maternal prepregnancy
      overweight was associated with reduced child verbal skills (unadjusted). However,
      after adjusting for confounders, this result was not consistently observed in
      both cohorts. Maternal overweight was also associated with child total behavior
      problems and externalizing problems even after adjusting for confounders.
      However, this was observed in Generation R only and was not replicated in the
      British Avon Longitudinal Study of Parents and Children. No associations of
      maternal overweight with child attention problems, emotional/internalizing
      problems, or nonverbal skills were observed in either cohort. Paternal overweight
      was not associated with any of the child outcomes but was also less strongly
      related to potential confounding factors than was maternal overweight.
      CONCLUSIONS: Overall, we found little consistent evidence of intrauterine effects
      of maternal prepregnancy overweight on child cognition and behavior. Some
      associations initially observed were not consistently replicated across cohorts
      or robust to adjustment for confounding factors and, thus, are likely to reflect
      confounding by socioeconomic or postnatal factors.

PMID- 21187311
TI  - National trends in visit rates and antibiotic prescribing for children with acute
      sinusitis.
AB  - OBJECTIVE: The heptavalent pneumococcal conjugate vaccine contributed to a
      substantial decrease in the number of ambulatory visits attributable to acute
      otitis media (AOM) and amoxicillin use for AOM increased after publication of
      American Academy of Pediatrics guidelines regarding AOM. Our objective was to
      determine whether similar trends occurred for children with acute sinusitis.
      METHODS: We analyzed data from the National Ambulatory Medical Care Survey and
      National Hospital Ambulatory Medical Care Survey (1998-2007), which are
      nationally representative surveys of office and emergency department visits. For
      children younger than 18 years with diagnosed acute sinusitis (N = 538), we
      examined time trends in visit rates and antibiotic prescribing. Multivariate
      logistic regression analyses were used to identify factors associated with narrow
      spectrum antibiotic prescribing. RESULTS: Between 1998 and 2007, the annual visit
      rate for acute sinusitis remained stable, ranging from 11 to 14 visits per 1000
      children (P = .67). No change occurred in the proportion of visits with receipt
      of an antibiotic (82%; P = .71); however, the proportion with receipt of
      amoxicillin increased from 19% to 58% during the study period (P < .01).
      Prescriptions for broader-spectrum agents, especially macrolides (18% overall),
      remained common. CONCLUSIONS: Unlike the visit rate for AOM, the visit rate for
      acute sinusitis among children did not decrease after introduction of the
      pneumococcal conjugate vaccine. Although prescriptions for amoxicillin increased
      in accordance with the guidelines, reducing unnecessary prescriptions for
      macrolides remains an important target for campaigns promoting judicious
      antibiotic use.

PMID- 21187313
TI  - Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection,
      wheezing, and asthma.
AB  - OBJECTIVE: Higher maternal intake of vitamin D during pregnancy is associated
      with a lower risk of wheezing in offspring. The relationship between cord-blood
      levels of 25-hydroxyvitamin D (25[OH]D) and childhood wheezing is unknown. We
      hypothesized that cord-blood levels would be inversely associated with risk of
      respiratory infection, wheezing, and asthma. PATIENTS AND METHODS: Cord blood
      from 922 newborns was tested for 25(OH)D. Parents were asked if their child had a
      history of respiratory infection at 3 months of age or a history of wheezing at
      15 months of age and then annually thereafter. Incident asthma was defined as
      doctor-diagnosed asthma by the time the child was 5 years old and reported
      inhaler use or wheezing since the age of 4 years. RESULTS: The median cord-blood
      level of 25(OH)D was 44 nmol/L (interquartile range: 29-78). Follow-up was 89% at
      the age of 5 years. Adjusting for the season of birth, 25(OH)D had an inverse
      association with risk of respiratory infection by 3 months of age (odds ratio:
      1.00 [reference] for >=75 nmol/L, 1.39 for 25-74 nmol/L, and 2.16 [95% confidence
      interval: 1.35-3.46] for <25 nmol/L). Likewise, cord-blood 25(OH)D levels were
      inversely associated with risk of wheezing by 15 months, 3 years, and 5 years of
      age (all P < .05). Additional adjustment for more than 12 potential confounders
      did not materially change these results. In contrast, we found no association
      between 25(OH)D levels and incident asthma by the age of 5 years. CONCLUSIONS:
      Cord-blood levels of 25(OH)D had inverse associations with risk of respiratory
      infection and childhood wheezing but no association with incident asthma.

PMID- 21187314
TI  - The tiniest babies: a registry of survivors with birth weight less than 400
      grams.
AB  - OBJECTIVE: The purpose of this project was to collect information on surviving
      infants with birth weights of <400 g. METHODS: A Web-based registry was started
      in 2000 after searching for published reports of infants who survived to hospital
      discharge despite being born at <400 g. Fifteen cases were identified from
      scientific and lay print and Web-based publications. Parents, patients, and
      health providers were invited to submit data on additional infants. In the case
      of submissions from parents or patients, the information was confirmed by
      communication with a treating physician. RESULTS: As of September 1, 2010, the
      Tiniest Babies Registry had compiled data on 110 patients born between 1936 and
      2010. The number of infants who survived each year increased since the early
      1990s. The infants in the registry weighed between 260 and 397 g at birth and had
      gestational ages from 21/7 to 34 weeks. Eighty-three (75%) of the patients are
      female. The 10 smallest infants are female, and the registry contains only 1 boy
      who was born weighing <300 g. The patients were born in 10 countries, including
      80 (73%) born in the United States. The information on long-term functional
      outcome and health outcomes is limited. Many patients have ongoing health and
      learning concerns, and most of those for whom growth data are available remain
      short in stature and underweight for their age. CONCLUSIONS: Survival of infants
      born weighing <400 g is rare but increasing. The Tiniest Babies Registry provides
      a repository for information about this remarkable group of infants.

PMID- 21187315
TI  - Variation in diagnosis of apnea in moderately preterm infants predicts length of
      stay.
AB  - OBJECTIVE: Apnea of prematurity is one of the most common diagnoses in the NICU.
      Because resolution of apnea is a usual precondition for discharge from the
      hospital, different monitoring practices might affect length of stay for
      premature infants. Our objective was to compare the proportion of 33 to 34 weeks'
      gestational age infants diagnosed with apnea in different NICUs and to assess
      whether variability in length of stay would be affected by the rate of documented
      apnea. METHODS: This was a prospective cohort study of moderately preterm infants
      who survived to discharge in 10 NICUs in Massachusetts and California. RESULTS:
      The study population comprised 536 infants born between 33 and 34/7 weeks of
      which 264 (49%) were diagnosed with apnea. The mean postmenstrual age at
      discharge was higher in infants diagnosed with apnea compared with those without
      apnea (36.4 +/- 1.3 vs 35.7 +/- 0.8; P < .001, analysis of variance). Significant
      inter-NICU variation existed in the proportion of infants diagnosed with apnea
      (range: 24%-76%; P < .001). Postmenstrual age at discharge also varied between
      NICUs (range: 35.5 +/- 0.6 to 36.7 +/- 1.5 weeks; P < .001). As much as 28% of
      the variability in postmenstrual age at discharge between NICUs could be
      explained by the variability in the proportion of infants diagnosed with apnea.
      CONCLUSIONS: NICUs vary in the proportion of moderately preterm infants diagnosed
      with apnea, which significantly affects length of stay. Standardization of
      monitoring practices and definition of clinically significant cardiorespiratory
      events could have a significant impact on reducing the length of stay in
      moderately preterm infants.

PMID- 21187316
TI  - Clinical report-bone densitometry in children and adolescents.
AB  - Concern for bone fragility in children and adolescents has led to increased
      interest in bone densitometry. Pediatric patients with genetic and acquired
      chronic diseases, immobility, and inadequate nutrition may fail to achieve the
      expected gains in bone size, mass, and strength, which leaves them vulnerable to
      fracture. In older adults, bone densitometry has been shown to predict fracture
      risk and reflect response to therapy. The role of densitometry in the management
      of children at risk of bone fragility is less certain. This clinical report
      summarizes the current knowledge about bone densitometry in the pediatric
      population, including indications for its use, interpretation of results, and its
      risks and costs. This report emphasizes consensus statements generated at the
      2007 Pediatric Position Development Conference of the International Society of
      Clinical Densitometry by an international panel of bone experts. Some of these
      recommendations are evidence-based, and others reflect expert opinion, because
      the available data are inadequate. The statements from this and other expert
      panels have provided general guidance to the pediatrician, but decisions about
      ordering and interpreting bone densitometry still require clinical judgment.
      Ongoing studies will help to better define the indications and best methods for
      assessing bone strength in children and the clinical factors that contribute to
      fracture risk.

PMID- 21187312
TI  - Early-childhood neurodevelopmental outcomes are not improving for infants born at
      <25 weeks' gestational age.
AB  - OBJECTIVE: We compared neurodevelopmental outcomes at 18 to 22 months' corrected
      age of infants born with extremely low birth weight at an estimated gestational
      age of <25 weeks during 2 periods: 1999-2001 (epoch 1) and 2002-2004 (epoch 2).
      PATIENTS AND METHODS: We conducted a multicenter, retrospective analysis of the
      Eunice Kennedy Shriver National Institute of Child Health and Human Development
      Neonatal Research Network. Perinatal and neonatal variables and outcomes were
      compared between epochs. Neurodevelopmental outcomes at 18 to 22 months'
      corrected age were evaluated with neurologic exams and Bayley Scales of Infant
      Development II. Logistic regression analyses determined the independent risk of
      epoch for adverse outcomes. RESULTS: Infant survival was similar between epochs
      (epoch 1, 35.4%, vs epoch 2, 32.3%; P = .09). A total of 411 of 452 surviving
      infants in epoch 1 and 405 of 438 surviving infants in epoch 2 were evaluated at
      18 to 22 months' corrected age. Cesarean delivery (P = .03), surgery for patent
      ductus arteriosus (P = .004), and late sepsis (P = .01) were more common in epoch
      2, but postnatal steroid use was dramatically reduced (63.5% vs 32.8%; P <
      .0001). Adverse outcomes at 18 to 22 months' corrected age were common in both
      epochs. Moderate-to-severe cerebral palsy was diagnosed in 11.1% of surviving
      infants in epoch 1 and 14.9% in epoch 2 (adjusted odds ratio [OR]: 1.52 [95%
      confidence interval (CI): 0.86-2.71]; P = .15), the Mental Developmental Index
      was <70 in 44.9% in epoch 1 and 51% in epoch 2 (OR: 1.30 [95% CI: 0.91-1.87]; P =
      .15), and neurodevelopmental impairment was diagnosed in 50.1% of surviving
      infants in epoch 1 and 58.7% in epoch 2 (OR: 1.4 [95% CI: 0.98-2.04]; P = .07).
      CONCLUSIONS: Early-childhood outcomes for infants born at <25 weeks' estimated
      gestational age were unchanged between the 2 periods.

PMID- 21187317
TI  - A structured career-immersion experience in the third year of residency training.
AB  - This is the second in a series of 4 articles that highlight the projects that
      were chosen for implementation by the Initiative for Innovation in Pediatric
      Education (IIPE) review committee in response to the 2009 call for letters of
      intent. The authors describe their progress to date in implementing a training
      experience that allows residents the opportunity to engage in a longitudinal
      clinical experience that is aligned with their ultimate career choice. Mentors
      play a critical role in this immersion experience.

PMID- 21187318
TI  - Antiviral CD8+ T cell effector activities in situ are regulated by target cell
      type.
AB  - Cytotoxic T lymphocytes (CTLs) play a prominent role in the resolution of viral
      infections through their capacity both to mediate contact-dependent lysis of
      infected cells and to release soluble proinflammatory cytokines and chemokines.
      The factors controlling these antiviral effector activities in vivo at infection
      sites are ill defined. Using a mouse model of influenza infection, we observed
      that the expression of CTL effector activity in the infected lungs is dictated by
      the target cell type encountered. CD45(+) lung infiltrating inflammatory
      mononuclear cells, particularly CD11c(hi) dendritic cells, trigger both CTL
      cytotoxicity and release of inflammatory mediators, whereas CD45(-) influenza
      infected respiratory epithelial cells stimulate only CTL cytotoxicity. CTL
      proinflammatory mediator release is modulated by co-stimulatory ligands (CD80 and
      CD86) expressed by the CD45(+) inflammatory cells. These findings suggest novel
      mechanisms of control of CTL effector activity and have potentially important
      implications for the control of excess pulmonary inflammation and immunopathology
      while preserving optimal viral clearance during respiratory virus infections.

PMID- 21187319
TI  - Leptin-dependent serotonin control of appetite: temporal specificity,
      transcriptional regulation, and therapeutic implications.
AB  - Recent evidence indicates that leptin regulates appetite and energy expenditure,
      at least in part by inhibiting serotonin synthesis and release from brainstem
      neurons. To demonstrate that this pathway works postnatally, we used a
      conditional, brainstem-specific mouse CreER(T2) driver to show that leptin
      signals in brainstem neurons after birth to decrease appetite by inhibiting
      serotonin synthesis. Cell-specific gene deletion experiments and
      intracerebroventricular leptin infusions reveal that serotonin signals in arcuate
      nuclei of the hypothalamus through the Htr1a receptor to favor food intake and
      that this serotonin function requires the expression of Creb, which regulates the
      expression of several genes affecting appetite. Accordingly, a specific
      antagonist of the Htr1a receptor decreases food intake in leptin-deficient but
      not in Htr1a(-/-) mice. Collectively, these results establish that leptin
      inhibition of serotonin is necessary to inhibit appetite postnatally and provide
      a proof of principle that selective inhibition of this pathway may be a viable
      option to treat appetite disorders.

PMID- 21187321
TI  - Galectin-9 regulates T helper cell function independently of Tim-3.
AB  - beta-Galactoside-binding lectin 9 (galectin-9) is a tandem repeat-type member of
      the galectin family. It was initially characterized as an eosinophil
      chemoattractant and an inducer of apoptosis in thymocytes. Subsequently, galectin
      9 was identified as a ligand for transmembrane immunoglobulin mucin domain 3 (Tim
      3), a type I glycoprotein induced on T cells during chronic inflammation. Work in
      autoimmune diseases and chronic viral infections have led to the current
      hypothesis that the function of Tim-3 is to limit immune responses. However, it
      is still not known to what degree these effects are due to the galectin-9/Tim-3
      interaction. In this study, we show that galectin-9 is not limited to the role of
      a pro-apoptotic agent, but that it can also induce the production of pro
      inflammatory cytokines from T helper cells. This effect is dose-dependent and
      does not require Tim-3. These findings suggest that the effects of galectin-9 on
      T cells are more complex than previously thought and are mediated by additional
      receptors apart from Tim-3.

PMID- 21187320
TI  - Activation of vascular BK channels by docosahexaenoic acid is dependent on
      cytochrome P450 epoxygenase activity.
AB  - AIMS: n-3 Polyunsaturated fatty acids (PUFAs) are known to protect the
      cardiovascular system and improve blood pressure control. These important dietary
      constituents are converted into bioactive metabolites, but their role in
      regulation of the cardiovascular system is unclear. In particular, the functions
      of the cytochrome P450 (CYP) metabolites of n-3 PUFAs remain virtually
      unexplored. In this study, we examined the effects of docosahexaenoic acid (DHA)
      on the regulation of large-conductance calcium-activated potassium (BK) channel
      activities in coronary arterial smooth muscle cells. METHODS AND RESULTS: Using
      whole-cell patch-clamp techniques, we found that DHA is a potent activator of BK
      currents in rat coronary arterial smooth muscle cells with an EC(50) of 0.23 +/-
      0.03 uM. This effect was abolished by pre-incubation with the CYP epoxygenase
      inhibitor, SKF525A (10 uM). The effects of DHA on the BK channels were reproduced
      by 16,17-epoxydocosapentaenoic acid (16,17-EpDPE) with an EC(50) of 19.7 +/- 2.8
      nM. The physiological role of the CYP metabolites of DHA was confirmed by
      measuring DHA-mediated vasodilatation in isolated rat coronary arteries. DHA
      dilated pressurized isolated coronary arteries in a dose-dependent manner, and
      the DHA effects were abolished after pre-treatment with SKF525A (10 uM) or with
      iberiotoxin (100 nM). In addition, 16,17-EpDPE directly produced coronary
      vasodilatation that was iberiotoxin sensitive. CONCLUSION: These results suggest
      that DHA-mediated vasodilatation is mediated through CYP epoxygenase metabolites
      by activation of vascular BK channels.

PMID- 21187325
TI  - Ramanujan Hegde: The prion puzzle and protein translocation. Interview by Caitlin
      Sedwick.

PMID- 21187326
TI  - Culling sick mitochondria from the herd.
AB  - The PINK1-Parkin pathway plays a critical role in mitochondrial quality control
      by selectively targeting damaged mitochondria for autophagy. In this issue,
      Tanaka et al. (2010. J. Cell Biol. doi: 10.1083/jcb.201007013) demonstrate that
      the AAA-type ATPase p97 acts downstream of PINK1 and Parkin to segregate fusion
      incompetent mitochondria for turnover. p97 acts by targeting the mitochondrial
      fusion-promoting factor mitofusin for degradation through an endoplasmic
      reticulum-associated degradation (ERAD)-like mechanism.

PMID- 21187327
TI  - The intracellular dynamic of protein palmitoylation.
AB  - S-palmitoylation describes the reversible attachment of fatty acids
      (predominantly palmitate) onto cysteine residues via a labile thioester bond.
      This posttranslational modification impacts protein functionality by regulating
      membrane interactions, intracellular sorting, stability, and membrane
      micropatterning. Several recent findings have provided a tantalizing insight into
      the regulation and spatiotemporal dynamics of protein palmitoylation. In
      mammalian cells, the Golgi has emerged as a possible super-reaction center for
      the palmitoylation of peripheral membrane proteins, whereas palmitoylation
      reactions on post-Golgi compartments contribute to the regulation of specific
      substrates. In addition to palmitoylating and depalmitoylating enzymes,
      intracellular palmitoylation dynamics may also be controlled through interplay
      with distinct posttranslational modifications, such as phosphorylation and
      nitrosylation.

PMID- 21187328
TI  - SIRT1 contributes to telomere maintenance and augments global homologous
      recombination.
AB  - Yeast Sir2 deacetylase is a component of the silent information regulator (SIR)
      complex encompassing Sir2/Sir3/Sir4. Sir2 is recruited to telomeres through Rap1,
      and this complex spreads into subtelomeric DNA via histone deacetylation.
      However, potential functions at telomeres for SIRT1, the mammalian orthologue of
      yeast Sir2, are less clear. We studied both loss of function (SIRT1 deficient)
      and gain of function (SIRT1(super)) mouse models. Our results indicate that SIRT1
      is a positive regulator of telomere length in vivo and attenuates telomere
      shortening associated with aging, an effect dependent on telomerase activity.
      Using chromatin immunoprecipitation assays, we find that SIRT1 interacts with
      telomeric repeats in vivo. In addition, SIRT1 overexpression increases homologous
      recombination throughout the entire genome, including telomeres, centromeres, and
      chromosome arms. These findings link SIRT1 to telomere biology and global DNA
      repair and provide new mechanistic explanations for the known functions of SIRT1
      in protection from DNA damage and some age-associated pathologies.

PMID- 21187329
TI  - Protein phosphatase 6 regulates mitotic spindle formation by controlling the T
      loop phosphorylation state of Aurora A bound to its activator TPX2.
AB  - Many protein kinases are activated by a conserved regulatory step involving T
      loop phosphorylation. Although there is considerable focus on kinase activator
      proteins, the importance of specific T-loop phosphatases reversing kinase
      activation has been underappreciated. We find that the protein phosphatase 6
      (PP6) holoenzyme is the major T-loop phosphatase for Aurora A, an essential
      mitotic kinase. Loss of PP6 function by depletion of catalytic or regulatory
      subunits interferes with spindle formation and chromosome alignment because of
      increased Aurora A activity. Aurora A T-loop phosphorylation and the stability of
      the Aurora A-TPX2 complex are increased in cells depleted of PP6 but not other
      phosphatases. Furthermore, purified PP6 acts as a T-loop phosphatase for Aurora A
      TPX2 complexes in vitro, whereas catalytically inactive mutants cannot
      dephosphorylate Aurora A or rescue the PPP6C depletion phenotype. These results
      demonstrate a hitherto unappreciated role for PP6 as the T-loop phosphatase
      regulating Aurora A activity during spindle formation and suggest the general
      importance of this form of regulation.

PMID- 21187330
TI  - Nessun Dorma, a novel centralspindlin partner, is required for cytokinesis in
      Drosophila spermatocytes.
AB  - Cytokinesis, the final step of cell division, usually ends with the abscission of
      the two daughter cells. In some tissues, however, daughter cells never completely
      separate and remain interconnected by intercellular bridges or ring canals. In
      this paper, we report the identification and analysis of a novel ring canal
      component, Nessun Dorma (Nesd), isolated as an evolutionarily conserved partner
      of the centralspindlin complex, a key regulator of cytokinesis. Nesd contains a
      pectin lyase-like domain found in proteins that bind to polysaccharides, and we
      present evidence that it has high affinity for beta-galactosides in vitro.
      Moreover, nesd is an essential gene in Drosophila melanogaster, in which it is
      required for completion of cytokinesis during male meiosis and possibly in female
      germline cells. Our findings indicate that Nesd is a novel carbohydrate-binding
      protein that functions together with centralspindlin in late cytokinesis, thus
      highlighting the importance of glycosylation in this process.

PMID- 21187331
TI  - Local clustering of transferrin receptors promotes clathrin-coated pit
      initiation.
AB  - Clathrin-mediated endocytosis (CME) is the major pathway for concentrative uptake
      of receptors and receptor-ligand complexes (cargo). Although constitutively
      internalized cargos are known to accumulate into maturing clathrin-coated pits
      (CCPs), whether and how cargo recruitment affects the initiation and maturation
      of CCPs is not fully understood. Previous studies have addressed these issues by
      analyzing the global effects of receptor overexpression on CME or CCP dynamics.
      Here, we exploit a refined approach using expression of a biotinylated
      transferrin receptor (bTfnR) and controlling its local clustering using mono- or
      multivalent streptavidin. We show that local clustering of bTfnR increased CCP
      initiation. By tracking cargo loading in individual CCPs, we found that bTfnR
      clustering preceded clathrin assembly and confirmed that bTfnR-containing CCPs
      mature more efficiently than bTfnR-free CCPs. Although neither the clustering nor
      the related changes in cargo loading altered the rate of CCP maturation, bTfnR
      containing CCPs exhibited significantly longer lifetimes than other CCPs within
      the same cell. Together these results demonstrate that cargo composition is a key
      source of the differential dynamics of CCPs.

PMID- 21187332
TI  - Targeted ablation of TRAF6 inhibits skeletal muscle wasting in mice.
AB  - Skeletal muscle wasting is a major human morbidity, and contributes to mortality
      in a variety of clinical settings, including denervation and cancer cachexia. In
      this study, we demonstrate that the expression level and autoubiquitination of
      tumor necrosis factor (alpha) receptor adaptor protein 6 (TRAF6), a protein
      involved in receptor-mediated activation of several signaling pathways, is
      enhanced in skeletal muscle during atrophy. Skeletal muscle-restricted depletion
      of TRAF6 rescues myofibril degradation and preserves muscle fiber size and
      strength upon denervation. TRAF6 mediates the activation of JNK1/2, p38 mitogen
      activated protein kinase, adenosine monophosphate-activated protein kinase, and
      nuclear factor kappaB, and induces the expression of muscle-specific E3 ubiquitin
      ligases and autophagy-related molecules in skeletal muscle upon denervation.
      Inhibition of TRAF6 also preserves the orderly pattern of intermyofibrillar and
      subsarcolemmal mitochondria in denervated muscle. Moreover, depletion of TRAF6
      prevents cancer cachexia in an experimental mouse model. This study unveils a
      novel mechanism of skeletal muscle atrophy and suggests that TRAF6 is an
      important therapeutic target to prevent skeletal muscle wasting.

PMID- 21187334
TI  - Nicotine up-regulates alpha4beta2 nicotinic receptors and ER exit sites via
      stoichiometry-dependent chaperoning.
AB  - The up-regulation of alpha4beta2* nicotinic acetylcholine receptors (nAChRs) by
      chronic nicotine is a cell-delimited process and may be necessary and sufficient
      for the initial events of nicotine dependence. Clinical literature documents an
      inverse relationship between a person's history of tobacco use and his or her
      susceptibility to Parkinson's disease; this may also result from up-regulation.
      This study visualizes and quantifies the subcellular mechanisms involved in
      nicotine-induced nAChR up-regulation by using transfected fluorescent protein
      (FP)-tagged alpha4 nAChR subunits and an FP-tagged Sec24D endoplasmic reticulum
      (ER) exit site marker. Total internal reflection fluorescence microscopy shows
      that nicotine (0.1 uM for 48 h) up-regulates alpha4beta2 nAChRs at the plasma
      membrane (PM), despite increasing the fraction of alpha4beta2 nAChRs that remain
      in near-PM ER. Pixel-resolved normalized Forster resonance energy transfer
      microscopy between alpha4-FP subunits shows that nicotine stabilizes the
      (alpha4)(2)(beta2)(3) stoichiometry before the nAChRs reach the trans-Golgi
      apparatus. Nicotine also induces the formation of additional ER exit sites
      (ERES). To aid in the mechanistic analysis of these phenomena, we generated a
      beta2(enhanced-ER-export) mutant subunit that mimics two regions of the beta4
      subunit sequence: the presence of an ER export motif and the absence of an ER
      retention/retrieval motif. The alpha4beta2(enhanced-ER-export) nAChR resembles
      nicotine-exposed nAChRs with regard to stoichiometry, intracellular mobility,
      ERES enhancement, and PM localization. Nicotine produces only small additional PM
      up-regulation of alpha4beta2(enhanced-ER-export) receptors. The experimental data
      are simulated with a model incorporating two mechanisms: (1) nicotine acts as a
      stabilizing pharmacological chaperone for nascent alpha4beta2 nAChRs in the ER,
      eventually increasing PM receptors despite a bottleneck(s) in ER export; and (2)
      removal of the bottleneck (e.g., by expression of the beta2(enhanced-ER-export)
      subunit) is sufficient to increase PM nAChR numbers, even without nicotine. The
      data also suggest that pharmacological chaperoning of nAChRs by nicotine can
      alter the physiology of ER processes.

PMID- 21187335
TI  - Mouse intact cardiac myocyte mechanics: cross-bridge and titin-based stress in
      unactivated cells.
AB  - A carbon fiber-based cell attachment and force measurement system was used to
      measure the diastolic stress-sarcomere length (SL) relation of mouse intact
      cardiomyocytes, before and after the addition of actomyosin inhibitors (2,3
      butanedione monoxime [BDM] or blebbistatin). Stress was measured during the
      diastolic interval of twitching myocytes that were stretched at 100% base
      length/second. Diastolic stress increased close to linear from 0 at SL 1.85 um to
      4.2 mN/mm(2) at SL 2.1 um. The actomyosin inhibitors BDM and blebbistatin
      significantly lowered diastolic stress by ~1.5 mN/mm(2) (at SL 2.1 um, ~30% of
      total), suggesting that during diastole actomyosin interaction is not fully
      switched off. To test this further, calcium sensitivity of skinned myocytes was
      studied under conditions that simulate diastole: 37 degrees C, presence of
      Dextran T500 to compress the myofilament lattice to the physiological level, and
      [Ca(2+)] from below to above 100 nM. Mean active stress was significantly
      increased at [Ca(2+)] > 55 nM (pCa 7.25) and was ~0.7 mN/mm(2) at 100 nM [Ca(2+)]
      (pCa 7.0) and ~1.3 mN/mm(2) at 175 nM Ca(2+) (pCa 6.75). Inhibiting active stress
      in intact cells attached to carbon fibers at their resting SL and stretching the
      cells while first measuring restoring stress (pushing outward) and then passive
      stress (pulling inward) made it possible to determine the passive cell's
      mechanical slack SL as ~1.95 um and the restoring stiffness and passive stiffness
      of the cells around the slack SL each as ~17 mN/mm(2)/um/SL. Comparison between
      the results of intact and skinned cells shows that titin is the main contributor
      to restoring stress and passive stress of intact cells, but that under
      physiological conditions, calcium sensitivity is sufficiently high for actomyosin
      interaction to contribute to diastolic stress. These findings are relevant for
      understanding diastolic function and for future studies of diastolic heart
      failure.

PMID- 21187337
TI  - Self-reported goal pursuit and purpose in life among people with dementia.
AB  - OBJECTIVES: Existential aspects of well-being are rarely studied in people with
      dementia, despite their reported importance. Self-report methods are also rarely
      used, despite the growing evidence for its use in mild-to-moderate dementia and
      the lack of concordance between self-reports and proxy reports of well-being. The
      goal of this study was to examine the relationship between one aspect of well
      being, purpose in life, and one of its predictors, goal pursuit, while employing
      the self-report of individuals with dementia. METHODS: Questionnaire and
      experimental methods were used to gauge the relationship between goal pursuit and
      purpose in life. The experimental portion was structured around creative drawing
      activities that are often used in adult day service centers. RESULTS: People with
      mild-to-moderate dementia were able to provide reliable self-report data on their
      well-being. A strong association between goal pursuit and purpose in life
      emerged, but dementia severity did not moderate this relationship. DISCUSSION:
      People with dementia who engage in goal-directed activity may experience a
      greater sense of purpose. Results from this study illuminate the experience of
      psychological well-being in dementia and may inform activity programming for this
      population.

PMID- 21187336
TI  - Massive calcium-activated endocytosis without involvement of classical endocytic
      proteins.
AB  - We describe rapid massive endocytosis (MEND) of >50% of the plasmalemma in baby
      hamster kidney (BHK) and HEK293 cells in response to large Ca transients.
      Constitutively expressed Na/Ca exchangers (NCX1) are used to generate Ca
      transients, whereas capacitance recording and a membrane tracer dye, FM 4-64, are
      used to monitor endocytosis. With high cytoplasmic adenosine triphosphate (ATP;
      >5 mM), Ca influx causes exocytosis followed by MEND. Without ATP, Ca transients
      cause only exocytosis. MEND can then be initiated by pipette perfusion of ATP,
      and multiple results indicate that ATP acts via phosphatidylinositol-bis 4,5
      phosphate (PIP(2)) synthesis: PIP(2) substitutes for ATP to induce MEND. ATP
      activated MEND is blocked by an inositol 5-phosphatase and by guanosine 5'-[gamma
      thio]triphosphate (GTPgammaS). Block by GTPgammaS is overcome by the
      phospholipase C inhibitor, U73122, and PIP(2) induces MEND in the presence of
      GTPgammaS. MEND can occur in the absence of ATP and PIP(2) when cytoplasmic free
      Ca is clamped to 10 uM or more by Ca-buffered solutions. ATP-independent MEND
      occurs within seconds during Ca transients when cytoplasmic solutions contain
      polyamines (e.g., spermidine) or the membrane is enriched in cholesterol.
      Although PIP(2) and cholesterol can induce MEND minutes after Ca transients have
      subsided, polyamines must be present during Ca transients. MEND can reverse over
      minutes in an ATP-dependent fashion. It is blocked by brief beta
      methylcyclodextrin treatments, and tests for involvement of clathrin, dynamins,
      calcineurin, and actin cytoskeleton were negative. Therefore, we turned to the
      roles of lipids. Bacterial sphingomyelinases (SMases) cause similar MEND
      responses within seconds, suggesting that ceramide may be important. However, Ca
      activated MEND is not blocked by reagents that inhibit SMases. MEND is abolished
      by the alkylating phospholipase A(2) inhibitor, bromoenol lactone, whereas
      exocytosis remains robust, and Ca influx causes MEND in cardiac myocytes without
      preceding exocytosis. Thus, exocytosis is not prerequisite for MEND. From these
      results and two companion studies, we suggest that Ca promotes the formation of
      membrane domains that spontaneously vesiculate to the cytoplasmic side.

PMID- 21187340
TI  - Inducible COX-2-dependent apoptosis in human ovarian cancer cells.
AB  - Resveratrol is a naturally occurring trihydroxyl-diphenylethylene compound that
      has been shown experimentally to have beneficial effects in the treatment of
      cancer and cardiovascular disease. Resveratrol induces programmed cell death
      (apoptosis) in these cells and activates important signal transducing proteins
      including extracellular signal-regulated kinases (ERKs) 1 and 2 in cancer cells.
      Resveratrol also causes nuclear accumulation of the enzyme cyclooxygenase (COX)-2
      and of the oncogene suppressor protein, p53. We have studied the molecular basis
      of the anticancer actions of resveratrol using human ovarian carcinoma (OVCAR-3)
      cells. Our findings include the following: (i) nuclear accumulation of COX-2 in
      resveratrol-treated cells is blocked by the ERK1/2 inhibitor, PD98059; (ii) an
      inhibitor of COX-2 activity, NS398, prevents accumulation of ERK1/2, COX-2,
      activated p53 and small ubiquitin-like modifier (SUMO-1) in the nucleus; (iii)
      apoptosis, quantitated by nucleosome enzyme-linked immunosorbent assay and the
      nuclear abundance of the pro-apoptotic protein, BcL-xs, were inhibited by NS398.
      This finding implicates nuclear COX-2 in p53-mediated apoptosis induced by
      resveratrol. Sumoylation is important to stabilization of p53 and a COX-2-SUMO-1
      interaction suggests sumoylation of COX-2 in resveratrol-treated cells and (iv)
      chromatin immunoprecipitation studies showed binding of induced nuclear COX-2 to
      the promoter region of PIG3 and Bax, pro-apoptotic gene targets of
      transcriptionally active p53. Nuclear accumulation of activated ERK1/2 and
      sumolyated COX-2 are essential to resveratrol-induced pSer-15-p53-mediated
      apoptosis in human ovarian cancer cells.

PMID- 21187338
TI  - Heterogeneities and consequences of Plasmodium species and hookworm coinfection:
      a population based study in Uganda.
AB  - BACKGROUND: Previous studies have suggested that helminth infection exacerbates
      malaria, but few existing epidemiological studies adequately control for
      infection heterogeneities and confounding factors. In this study, we investigate
      spatial and household heterogeneities, predictors, and consequences of Plasmodium
      species and hookworm coinfection in rural communities in Uganda. METHODS: A cross
      sectional study was conducted among 1770 individuals aged 0-88 years in 4
      villages. We recorded demographic, socioeconomic, and microgeographic factors
      during household surveys. We determined malaria parasitemia and hemoglobin
      concentration and collected stool samples on 2 consecutive days. For data
      analysis, we used a hierarchical, spatially explicit Bayesian framework. RESULTS:
      Prevalence of Plasmodium-hookworm coinfection was 15.5% overall and highest among
      school-aged children. We found strong evidence of spatial and household
      clustering of coinfection and an enduring positive association between Plasmodium
      species and hookworm infection among preschool-aged children (odds ratio [OR],
      2.36; 95% Bayesian credible interval [BCI], 1.26-4.30) and adults (OR, 2.09; 95%
      BCI, 1.35-3.16) but not among school-aged children. Coinfection was associated
      with lower hemoglobin level only among school-aged children. CONCLUSIONS:
      Plasmodium-hookworm coinfection exhibits marked age dependency and significant
      spatial and household heterogeneity, and among preschool-aged children and
      adults, occurs more than would be expected by chance. Such heterogeneities
      provide insight into factors underlying observed patterns and the design of
      integrated control strategies.

PMID- 21187341
TI  - The role of TRADD in TRAIL-induced apoptosis and signaling.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member
      of the TNF superfamily. TRAIL is promising for anticancer therapy because it
      induces apoptosis in cancer cells with little or no toxicity to normal cells;
      hence, TRAIL-receptor agonists are currently undergoing clinical trials for
      cancer treatment. However, many molecular signaling mechanisms in TRAIL signaling
      are not completely characterized. The functions of adaptor proteins, including
      TNF-receptor-associated death domain protein (TRADD) and receptor-interacting
      protein-1 (RIP1) in TRAIL signaling have been controversial. We demonstrate that
      while wild-type mouse embryonic fibroblasts (MEFs) are completely resistant to
      TRAIL-induced apoptosis, MEFs derived from Tradd(-/-) mice are hypersensitive to
      TRAIL (IC(50)~0.5 nM rmTRAIL, 24 h), an effect also seen in primary keratinocytes
      treated with TRAIL/CHX. Restoration of TRADD in Tradd(-/-) MEFs restores TRAIL
      resistance, indicating that TRADD plays a survival role in TRAIL signaling. We
      show that TRADD is recruited to the TRAIL-receptor complex, and RIP1 recruitment
      is mediated by TRADD. While early activation of the MAP kinase ERK is deficient
      in Tradd(-/-) cells, the main mechanism for enhanced TRAIL sensitivity is likely
      due to increased recruitment of FADD to the receptor complex, indicating that
      TRADD may limit FADD binding within the receptor complex and also mediate RIP1
      dependent nonapoptotic signaling events, thus reducing caspase activation and
      subsequent apoptosis. These novel findings have potential implications for cancer
      therapy using TRAIL-receptor agonists.

PMID- 21187342
TI  - Fluorescent proteins at a glance.

PMID- 21187344
TI  - Signalling to and from the secretory pathway.
AB  - For growth, survival, communication and homeostasis, cells transport a large
      number of proteins to the plasma membrane and the extracellular medium by using
      the secretory pathway. Consequently, to adapt to the surrounding environment and
      the different intracellular contexts, the secretory pathway needs to accommodate
      and respond to a plethora of endogenous and exogenous stimuli. It is now well
      established that several kinases, known to be activated by environmental stimuli,
      signal from the plasma membrane to the secretory pathway in order to remodel its
      architecture and modulate the cellular secretion capacity. By contrast, membranes
      of the early secretory pathway, similar to the endosomal system, can also
      initiate and modulate signalling cascades, thereby spatially organising cellular
      signalling and eliciting a different cellular outcome than when signalling is
      localised to the plasma membrane. This Commentary highlights recent contributions
      to our understanding of the mutual regulation of the secretory pathway and
      cellular signalling.

PMID- 21187343
TI  - The regulation of autophagy - unanswered questions.
AB  - Autophagy is an intracellular lysosomal (vacuolar) degradation process that is
      characterized by the formation of double-membrane vesicles, known as
      autophagosomes, which sequester cytoplasm. As autophagy is involved in cell
      growth, survival, development and death, the levels of autophagy must be properly
      regulated, as indicated by the fact that dysregulated autophagy has been linked
      to many human pathophysiologies, such as cancer, myopathies, neurodegeneration,
      heart and liver diseases, and gastrointestinal disorders. Substantial progress
      has recently been made in understanding the molecular mechanisms of the autophagy
      machinery, and in the regulation of autophagy. However, many unanswered questions
      remain, such as how the Atg1 complex is activated and the function of PtdIns3K is
      regulated, how the ubiquitin-like conjugation systems participate in autophagy
      and the mechanisms of phagophore expansion and autophagosome formation, how the
      network of TOR signaling pathways regulating autophagy are controlled, and what
      the underlying mechanisms are for the pro-cell survival and the pro-cell death
      effects of autophagy. As several recent reviews have comprehensively summarized
      the recent progress in the regulation of autophagy, we focus in this Commentary
      on the main unresolved questions in this field.

PMID- 21187346
TI  - Microtubule organization in the final stages of cytokinesis as revealed by cryo
      electron tomography.
AB  - The completion of cytokinesis is dominated by the midbody, a tightly-packed
      microtubule (MT)-based bridge that transiently connects the two daughter cells.
      Assembled from condensed, spindle-MTs and numerous associated proteins, the
      midbody gradually narrows down until daughter cell partitioning occurs at this
      site. Although described many years ago, detailed understanding of the abscission
      process remains lacking. Applying cryo-electron tomography to purified midbodies,
      in combination with fluorescence microscopy, we present here new insight into MT
      organization within the midbody. We find that the midbody is spatially divided
      into a core bundle of MTs that traverses the electron-dense overlap region
      (continuous MTs), surrounded by MTs that terminate within the overlap region
      (polar MTs). Residual continuous MTs remained intact up to the verge of
      abscission, whereas the residual polar MTs lost their organization and retreated
      from the overlap region at late cytokinesis stages. A detailed localization of
      the microtubule-bundling protein PRC1 supports the above notion. Our study thus
      provides a detailed account of the abscission process and suggests that the
      midbody, having acquired a distinct MT architecture as compared to the preceding
      central spindle, actively facilitates the final stage of cytokinesis.

PMID- 21187345
TI  - Slit-2 repels the migration of olfactory ensheathing cells by triggering Ca2+
      dependent cofilin activation and RhoA inhibition.
AB  - Olfactory ensheathing cells (OECs) migrate from the olfactory epithelium towards
      the olfactory bulb during development. However, the guidance mechanism for OEC
      migration remains a mystery. Here we show that migrating OECs expressed the
      receptor of the repulsive guidance factor Slit-2. A gradient of Slit-2 in front
      of cultured OECs first caused the collapse of the leading front, then the
      reversal of cell migration. These Slit-2 effects depended on the Ca(2+) release
      from internal stores through inositol (1,4,5)-triphosphate receptor channels.
      Interestingly, in response to Slit-2 stimulation, collapse of the leading front
      required the activation of the F-actin severing protein cofilin in a Ca(2+)
      dependent manner, whereas the subsequent reversal of the soma migration depended
      on the reversal of RhoA activity across the cell. Finally, the Slit-2-induced
      repulsion of cell migration was fully mimicked by co-application of inhibitors of
      F-actin polymerization and RhoA kinase. Our findings revealed Slit-2 as a
      repulsive guidance factor for OEC migration and an unexpected link between Ca(2+)
      and cofilin signaling during Slit-2-triggered repulsion.

PMID- 21187347
TI  - Color and material perception: achievements and challenges.
AB  - There is a large literature characterizing human perception of the lightness and
      color of matte surfaces arranged in coplanar arrays. In the past ten years
      researchers have begun to examine perception of lightness and color using wider
      ranges of stimuli intended to better approximate the conditions of everyday
      viewing. One emerging line of research concerns perception of lightness and color
      in scenes that approximate the three-dimensional environment we live in, with
      objects that need not be matte or coplanar and with geometrically complex
      illumination. A second concerns the perception of material surface properties
      other than color and lightness, such as gloss or roughness. This special issue
      features papers that address the rich set of questions and approaches that have
      emerged from these new research directions. Here, we briefly describe the
      articles in the issue and their relation to previous work.

PMID- 21187348
TI  - Recognizing real materials from their glossy appearance.
AB  - In everyday life, the visual system is remarkably good at recognizing materials
      across a wide range of viewing conditions. This paper addresses the problem of
      identifying real samples of materials from appearance. Here, we consider gloss as
      an appearance attribute that could reveal certain information about object
      properties. We prepared twelve samples of glass and PMMA and eroded these using
      different agents. The gloss and haze of the samples were measured at 60 degrees
      via a gloss meter. For all samples, the surface roughness properties were
      measured. Microfacet distributions were derived from measured BRDFs using an
      inverted microfacet model. We conducted a visual ranking experiment using the
      pair comparison method. The psychophysical gloss ratings correlate well with the
      60 degrees gloss index. Principal component analysis of the psychophysical
      results revealed a somewhat more complicated picture in which three components
      seem to play a role. We conclude that observers can apprehend the physical nature
      of the surface of real objects from features that are included in the BRDF and
      available in the gloss appearance.

PMID- 21187349
TI  - Adaptable mechanisms sensitive to surface color in human vision.
AB  - "Color constancy" refers to our ability to recognize the color of a surface
      despite changes in illumination. A range of cues and mechanisms, from receptoral
      adaptation to higher order cognitive cues, is thought to contribute to our color
      constancy ability. Here we used psychophysical adaptation to probe for an
      adaptable representation of surface color. We used stimuli that were matched for
      cone contrast when averaged over time but were consistent with either a constant
      scene under changing illumination or a changing scene. The color opponent
      aftereffect during adaptation to the constant scene was greater than that induced
      by the changing scene stimulus. Since the stimuli were matched for the responses
      they would elicit in receptoral mechanisms, the increased aftereffect in the
      constant scene condition cannot be wholly attributed to adaptation of receptors
      and neural mechanisms responsive to raw quantal catch. We interpret our result as
      most parsimoniously explained by the existence of adaptable mechanisms responsive
      to surface color, most likely located in early visual cortex.

PMID- 21187350
TI  - Categorical color constancy for real surfaces.
AB  - In everyday experience, perceived colors of objects remain approximately constant
      under changes in illumination. This constancy is helpful for identifying objects
      across viewing conditions. Studies on color constancy often employ monitor
      simulations of illumination and reflectance changes. Real scenes, however, have
      features that might be important for color constancy but that are in general not
      captured by monitor displays. Here, we investigate categorical color constancy
      employing real surfaces and real illuminants in a rich viewing context. Observers
      sorted 450 Munsell samples into the 11 basic color categories under a daylight
      and four filtered daylight illuminants. We additionally manipulated illuminant
      cues from the local surround. Color constancy as quantified both with a
      classification consistency index and a standard color constancy index was high in
      both cue conditions. Observers generally classified colors with the same
      precision across different illuminants as across repetitions for the daylight
      illuminant. Moreover, the pattern of classification consistency in terms of
      stimulus hue, value, and chroma was similar when comparing different observers
      for the daylight illuminant and when comparing individual observers across
      different illuminants. We conclude that color categorization is robust under
      illuminant changes as well as across observers, thus potentially serving both
      object identification and communication.

PMID- 21187351
TI  - Evolutionary changes of the target sites of two microRNAs encoded in the Hox gene
      cluster of Drosophila and other insect species.
AB  - MicroRNAs (miRs) are noncoding RNAs that regulate gene expression at the post
      transcriptional level. In animals, the target sites of a miR are generally
      located in the 3' untranslated regions (UTRs) of messenger RNAs. However, how the
      target sites change during evolution is largely unknown. MiR-iab-4 and miR-iab
      4as are known to regulate the expression of two Hox genes, Abd-A and Ubx, in
      Drosophila melanogaster. We have therefore studied the evolutionary changes of
      these two miR genes and their target sites of the Hox genes in Drosophila, other
      insect species, and Daphnia. Our homology search identified a single copy of each
      miR gene located in the same genomic position of the Hox gene cluster in all
      species examined. The seed nucleotide sequence was also the same for all species.
      Searching for the target sites in all Hox genes, we found several target sites of
      miR-iab-4 and miR-iab-4as in Antp in addition to Abd-A and Ubx in most insect
      species examined. Our phylogenetic analysis of target sites in Abd-A, Ubx, and
      Antp showed that the old target sites, which existed before the divergence of the
      12 Drosophila species, have been well maintained in most species under purifying
      selection. By contrast, new target sites, which were generated during Drosophila
      evolution, were often lost in some species and mostly located in unalignable
      regions of the 3' UTRs. These results indicate that these regions can be a
      potential source of generating new target sites, which results in multiple target
      genes for each miR in animals.

PMID- 21187352
TI  - 2010 European guideline for the management of Chlamydia trachomatis infections.
AB  - This guideline aims to provide comprehensive information regarding the management
      of infections caused by Chlamydia trachomatis in European countries. The
      recommendations contain important information for physicians and laboratory staff
      working with sexually transmitted infections (STIs) and/or STI-related issues.
      Individual European countries may be required to make minor national adjustments
      to this guideline as some of the tests or specific local data may not be
      accessible, or because of specific laws.

PMID- 21187353
TI  - Virological response with fully active etravirine: pooled results from the DUET-1
      and DUET-2 trials.
AB  - The objective of this subanalysis of the Phase III DUET trials was to examine
      virological response to an etravirine-containing regimen in patients harbouring
      virus fully sensitive to etravirine. Full etravirine sensitivity was defined as
      fold change in 50% effective concentration (FC) <=3 or weighted genotypic score
      <=2. At Week 48 in the etravirine group, 74% of patients with etravirine FC <=3
      and 77% with etravirine genotypic score <=2 had viral load <50 HIV-1 RNA
      copies/mL, versus 48% and 46%, respectively, in the placebo group (P < 0.0001).
      Response rates increased with baseline phenotypic sensitivity score, but were
      consistently higher with etravirine (56-82%) than placebo (2-72%). Similar
      observations were made in patients harbouring virus with full etravirine and
      darunavir sensitivity. Our findings support current recommendations to include
      three active agents in treatment-experienced patients' regimens.

PMID- 21187354
TI  - Effect of Ethiopian multiflora honey on fluconazole-resistant Candida species
      isolated from the oral cavity of AIDS patients.
AB  - This study aimed to determine the antifungal effect of Ethiopian multiflora honey
      against Candida species isolated from the oral cavity of AIDS patients. Oral
      rinses were obtained from 13 AIDS patients and cultured on CHROMagar plates at 37
      degrees C for 48 hours. Candida species were identified by microbiological and
      molecular techniques. The antifungal effect of the honey sample on Candida was
      investigated by an agar dilution technique. Susceptibility of the Candida species
      to fluconazole was tested following a semi-modified microdilution method. Growth
      of both fluconazole-susceptible and -resistant Candida species was inhibited with
      a minimum fungicidal concentration (MFC) of 35-40% (v/v) honey. The MFC of
      different Candida species was not significantly different (P > 0.05). From the
      total of 25 Candida isolates tested for susceptibility, 11 (44%), eight (32%) and
      six (24%) of the isolates were sensitive (minimum inhibitory concentrations
      [MICs] < 8 ug/mL), susceptible (dose-dependent: MICs 16-32 ug/mL) and resistant
      (MICs > 64 ug/mL) to fluconazole, respectively. Ethiopian multiflora honey has
      antifungal activity against fluconazole-resistant Candida species isolated from
      the oral cavity of AIDS patients. This supports the existing folkloric practice
      of using honey to treat oral lesions. Nevertheless, identification of the
      bioactive agents in honey, their clinical evaluation and pharmacological
      standardization are crucial.

PMID- 21187355
TI  - High-risk sex among mobile female sex workers in the context of jatras (religious
      festivals) in Karnataka, India.
AB  - Jatras (religious festivals) represent venues for female sex workers (FSWs) to
      meet potential clients in an environment of anonymity. Data from a survey
      conducted among 1499 mobile FSWs in Karnataka, India were analysed using
      bivariate and multivariate analysis. Overall, 31% of mobile FSWs reported
      attending jatras in the previous year. Women who sold sex at jatras tended to
      practice sex work in public places, in their own homes or on highways. Jatra
      attendees reported lower condom use with their last commercial sexual partners at
      their usual places of sex work. Jatra-related mobility was a significant
      predictor of non-condom use at their usual place of residence, after controlling
      for sociodemographic, sex work-related, HIV vulnerability and programme exposure
      variables. Moreover, only 13% of FSWs used condoms consistently at jatras. Condom
      availability and accessibility at jatras should be a priority for HIV prevention
      programmes, and such programmes should make efforts to introduce outreach
      activities at jatras.

PMID- 21187356
TI  - Assessment of hospitalizations among HIV patients in the UK: a national cross
      sectional survey.
AB  - This 2007 cross-sectional survey is illustrative of UK HIV hospitalization
      patterns. Data were received for 255 inpatients of whom 43.9% had AIDS-defining
      illnesses (ADIs). A total of 56.3% had CD4 counts <200 mm(3) and 17% were
      diagnosed with HIV on their current admission. In those diagnosed for >3 months
      with CD4 < 200/mm(3) (90/188), 47% were not on combination antiretroviral therapy
      (cART). ADIs still make up a substantial proportion of inpatient work in the UK
      and late diagnosis and failure to benefit from cART remain too common.

PMID- 21187357
TI  - Use of computerized medical records to determine the feasibility of testing for
      chlamydia without patients seeing a practitioner.
AB  - The proportion of clinically important diagnoses in a low-risk, asymptomatic
      population who use a computer-assisted self-interview (CASI) to assess risk was
      needed to determine optimal health service delivery. Medical records were
      retrospectively analysed between July 2008 and June 2009 for risk characteristics
      and diagnoses. A total of 7733 new patients completed a CASI, of whom 1060 were
      asymptomatic heterosexuals. From this low-risk group, 26 diagnoses were made on
      the day of presentation, including 22 cases of genital warts (2.08% [95%
      confidence interval (CI) 1.22-2.93]), three cases of genital herpes (0.28% [95%
      CI 0.055-0.82]) and one case of unintended pregnancy (0.094% [95% CI 0.0061
      0.52]). Additionally, there were 54 cases of chlamydia detected (5.09% [95% CI
      3.77-6.42]). As chlamydia is effectively diagnosed and managed from self
      collected samples, patient review is not always required. This study provides
      evidence for an express testing service for chlamydia to streamline the screening
      of low-risk, asymptomatic heterosexual patients as identified by CASI without the
      need to for a traditional face-to-face consultation.

PMID- 21187358
TI  - Preliminary assessment of Treponema pallidum-specific IgM antibody detection and
      a new rapid point-of-care assay for the diagnosis of syphilis in human
      immunodeficiency virus-1-infected patients.
AB  - The aims of the study were to assess whether Treponema pallidum-specific IgM may
      provide a useful marker of infectious syphilis in human immunodeficiency virus
      (HIV)-infected patients, and to compare the performance of a prototype IgM-rapid
      point-of-care test (PoCT) with a standard IgM-enzyme immunoassay (EIA). Twenty
      samples from HIV-infected patients with untreated syphilis (n = 4 primary
      syphilis, n = 11 secondary and n = 5 early latent) and 51 follow-up samples at
      three, six or 12 months after treatment were tested for the presence of IgM with
      the Mercia-EIA (Microgen Bioproducts Ltd, Camberley, UK) and a prototype PoCT
      (Select Vaccines Ltd, Melbourne, Australia). Although sample numbers were small,
      IgM detection by EIA appears to be a reliable marker for untreated syphilis in
      HIV-infected patients with primary (4/4 IgM-positive) or secondary syphilis
      (10/11 IgM-positive, 1/11 equivocal). After treatment, IgM was no longer detected
      after three months in the majority of patients (87%) and was either negative or
      equivocal in all patients after six and 12 months. The overall sensitivity of the
      IgM-PoCT was 82% and varied with clinical stage, being highest in secondary
      (10/10 EIA positives) but lower in primary (2/4 EIA positives) and early latent
      syphilis (2/3 EIA positives). Overall specificity was 95%. Rapid detection of IgM
      would enable clinicians to distinguish between past-treated and infectious
      syphilis and allow for diagnosis and treatment in a single visit.

PMID- 21187359
TI  - Incidence and risk factors associated with lost to follow-up in a Belgian cohort
      of HIV-infected patients treated with highly active antiretroviral therapy.
AB  - Being lost to follow-up (LTFU) is a major problem in caring for persons with HIV
      infection. We describe the proportions and characteristics of LTFU in a Belgian
      outpatient HIV clinic. All patients treated with highly active antiretroviral
      therapy (HAART) who attended at least two consultations were included. Patients
      not returning within the following year were considered LTFU. Multivariate
      analysis using logistic regression was performed. The LTFU rate was 5.5% on
      average and remained stable over the years. Patients LTFU were more often
      intravenous drug users (odds ratio [OR] = 3.48), not covered by health insurance
      (OR = 6.69), living outside the province (OR = 1.49) and treated with a complex
      initial HAART regimen (OR = 5.80). Increased age was also associated with a
      higher risk of LTFU. Patients at risk for LTFU after starting HAART should be the
      targeted for reinforced counselling and HIV treatment centres should establish
      systems to trace patients LTFU.

PMID- 21187360
TI  - Is screening for pharyngeal Chlamydia trachomatis warranted in high-risk groups?
AB  - A recent survey reported that 36% of UK genitourinary medicine clinics offer
      testing for pharyngeal Chlamydia trachomatis (CT). Screening at this site is
      targeted at high-risk groups attending our centre, including female sex workers
      (FSWs) and male sex workers (MSWs). A total of 2406 patients were screened
      between November 2006 and October 2007. A retrospective case-note review was
      performed for positive cases. The prevalence of pharyngeal CT was 1.9% in both
      men and women. The mean number of sexual partners reported in the preceding three
      months was 168 and 56 for FSWs and MSWs, respectively. Lack of consistent condom
      use and high numbers of sexual partners identify this population as potential
      core transmitters of infection. While the British Association of Sexual Health
      and HIV (BASHH) guidelines do not recommend routine screening for pharyngeal CT,
      there may be a role in selected high-risk populations.

PMID- 21187361
TI  - An audit on the management of lymphogranuloma venereum in a sexual health clinic
      in London, UK.
AB  - We performed an audit on the management of lymphogranuloma venereum (LGV) against
      the British Association of Sexual Health and HIV (BASHH) guidelines. Sixty-three
      cases of LGV were diagnosed in 60 men who have sex with men (MSM). Fifty-six out
      of 63 (89%) episodes were treated in accordance with the guidelines. Although all
      eligible patients were offered an HIV test, 10% and 29% of patients were not
      offered syphilis or hepatitis C tests, respectively, at the time of LGV
      diagnosis. Partner notification was not possible in a third of cases. Several
      patients were re-infected with rectal Chlamydia trachomatis in the three months
      following LGV diagnosis, emphasizing the importance of rescreening to detect new
      infections as well as treatment failures in MSM at ongoing high risk of sexually
      transmitted infection acquisition.

PMID- 21187362
TI  - A case of multidrug resistance in the central nervous system.
AB  - HIV-1 infection may persist in the central nervous system (CNS) despite
      antiretroviral therapy. We present a case of severe cognitive decline in a man
      with HIV-1 infection on a fully active regimen for five years. All infective
      causes were excluded. Despite fully suppressed virus in the blood, HIV RNA in the
      cerebrospinal fluid measured 3.52 log(10) RNA copies/mL and genotyping of this
      sample showed an extensive pattern of resistance. This suggested that either the
      antiretroviral agents were not adequately penetrating the CNS or the CNS had
      resistant virus as a result of adherence problems. This case highlights the
      possibility that drug-resistant mutations may develop in the CNS compartment
      while plasma virus remains suppressed.

PMID- 21187363
TI  - Penicillium marneffei infection presenting as an immune reconstitution
      inflammatory syndrome in an HIV patient.
AB  - We describe a case of Penicillium marneffei infection acquired in Thailand,
      manifesting as an immune reconstitution inflammatory syndrome (IRIS) in a
      Caucasian man with advanced HIV-related immunosuppression (CD4 72 cells/mm3).
      Initial presentation was consistent with Pneumocystis jirovecii pneumonia, and
      empirical co-trimoxazole resulted in clinical improvement. One month after
      initiating antiretroviral therapy (ART), an enlarging scaly lesion on his
      forehead and erythematous nodules on his face, trunk and limbs developed. P.
      marneffei was isolated from a skin aspirate. Response to antifungal therapy was
      complicated by drug interactions but cure was complete after four months of
      treatment. Few cases of IRIS associated with P. marneffei have been reported.

PMID- 21187364
TI  - Severe raltegravir-associated rhabdomyolysis: a case report and review of the
      literature.
AB  - Raltegravir (RAL), an HIV integrase inhibitor, may uncommonly induce an increase
      of serum creatine kinase (CK) both in naive and antiretroviral (ARV)-experienced
      HIV-positive patients. We report the case of severe rhabdomyolysis requiring
      hospitalization in an ARV-experienced HIV/hepatitis C co-infected patient treated
      with a RAL-containing drug regimen. Factors favouring a severe clinical
      occurrence of RAL-induced rhabdomyolysis from cases reported in literature are
      described.

PMID- 21187365
TI  - The HPV vaccination programme in the UK: the opinion of a body of consultants in
      a district general hospital.

PMID- 21187366
TI  - Response to Li et al.: evaluation of a school-based HIV/AIDS peer-led prevention
      programme.

PMID- 21187367
TI  - Buschke-Lowenstein tumour.

PMID- 21187368
TI  - Sexual assault guidelines.

PMID- 21187369
TI  - The high-affinity cAMP-specific phosphodiesterase 8B controls steroidogenesis in
      the mouse adrenal gland.
AB  - The functions of the phosphodiesterase 8B (PDE8) family of phosphodiesterases
      have been largely unexplored because of the unavailability of selective
      pharmacological inhibitors. Here, we report a novel function of PDE8B as a major
      regulator of adrenal steroidogenesis using a genetically ablated PDE8B mouse
      model as well as cell lines treated with either a new PDE8-selective inhibitor or
      a short hairpin RNA (shRNA) construct against PDE8B. We demonstrate that PDE8B is
      highly enriched in mouse adrenal fasciculata cells, and show that PDE8B knockout
      mice have elevated urinary corticosterone as a result of adrenal hypersensitivity
      toward adrenocorticotropin. Likewise, ablation of PDE8B mRNA transcripts by an
      shRNA construct potentiates steroidogenesis in the commonly used Y-1 adrenal cell
      line. We also observed that the PDE8-selective inhibitor (PF-04957325)
      potentiates adrenocorticotropin stimulation of steroidogenesis by increasing cAMP
      dependent protein kinase activity in both primary isolated adrenocortical cells
      and Y-1 cells. It is noteworthy that PDE8s have their greatest control under low
      adrenocorticotropin-stimulated conditions, whereas other higher K(m) PDE(s)
      modulate steroidogenesis more effectively when cells are fully stimulated.
      Finally, both genetic ablation of PDE8B and long-term pharmacological inhibition
      of PDE8s cause increased expression of steroidogenic enzymes. We conclude that
      PDE8B is a major regulator of one or more pools of cAMP that promote
      steroidogenesis via both short- and long-term mechanisms. These findings further
      suggest PDE8B as a potential therapeutic target for the treatment of several
      different adrenal diseases.

PMID- 21187370
TI  - Application of artificial neural network models in occupational safety and health
      utilizing ordinal variables.
AB  - Safety professionals and practitioners are always searching for methods to
      accurately assess the association between exposures and possible occupational
      disorders or diseases and predict the outcome of any variable. Statistical
      analysis and logistic regression (LR) in particular are among the most popular
      tools being used today. Artificial neural network (ANN) models are another method
      of predicting outcomes, which are gradually finding their way into the safety
      field. Limited studies have shown that they are capable of predicting outcomes
      more accurately than LR, but they have been tested either on continuous or on
      dichotomous variables or combinations of them. The objective of this research was
      to demonstrate that ANN models can perform better than LR models with data sets
      comprised of all ordinal variables, which has not been done so far. The data set
      used in this research was collected from construction workers using the Work
      Compatibility questionnaire. The data set contained only ordinal variables both
      as input (exposure) and as output (outcome) variables. LR models and ANN models
      were constructed using the same data set and the performance of all models was
      compared by using the log-likelihood ratio. The result of this study showed that
      ANN models performed significantly better than LR models with a data set of all
      ordinal variables as well as other types of variables such as dichotomous and
      continuous.

PMID- 21187371
TI  - Targeting membrane heat-shock protein 70 (Hsp70) on tumors by cmHsp70.1 antibody.
AB  - Immunization of mice with a 14-mer peptide TKDNNLLGRFELSG, termed "TKD,"
      comprising amino acids 450-461 (aa(450-461)) in the C terminus of inducible
      Hsp70, resulted in the generation of an IgG1 mouse mAb cmHsp70.1. The epitope
      recognized by cmHsp70.1 mAb, which has been confirmed to be located in the TKD
      sequence by SPOT analysis, is frequently detectable on the cell surface of human
      and mouse tumors, but not on isogenic cells and normal tissues, and membrane
      Hsp70 might thus serve as a tumor-specific target structure. As shown for human
      tumors, Hsp70 is associated with cholesterol-rich microdomains in the plasma
      membrane of mouse tumors. Herein, we show that the cmHsp70.1 mAb can selectively
      induce antibody-dependent cellular cytotoxicity (ADCC) of membrane Hsp70(+) mouse
      tumor cells by unstimulated mouse spleen cells. Tumor killing could be further
      enhanced by activating the effector cells with TKD and IL-2. Three consecutive
      injections of the cmHsp70.1 mAb into mice bearing CT26 tumors significantly
      inhibited tumor growth and enhanced the overall survival. These effects were
      associated with infiltrations of NK cells, macrophages, and granulocytes. The
      Hsp70 specificity of the ADCC response was confirmed by preventing the antitumor
      response in tumor-bearing mice by coinjecting the cognate TKD peptide with the
      cmHsp70.1 mAb, and by blocking the binding of cmHsp70.1 mAb to CT26 tumor cells
      using either TKD peptide or the C-terminal substrate-binding domain of Hsp70.

PMID- 21187372
TI  - Distortions of mind perception in psychopathology.
AB  - It has long been known that psychopathology can influence social perception, but
      a 2D framework of mind perception provides the opportunity for an integrative
      understanding of some disorders. We examined the covariation of mind perception
      with three subclinical syndromes--autism-spectrum disorder, schizotypy, and
      psychopathy--and found that each presents a unique mind-perception profile.
      Autism-spectrum disorder involves reduced perception of agency in adult humans.
      Schizotypy involves increased perception of both agency and experience in
      entities generally thought to lack minds. Psychopathy involves reduced perception
      of experience in adult humans, children, and animals. Disorders are
      differentially linked with the over- or underperception of agency and experience
      in a way that helps explain their real-world consequences.

PMID- 21187373
TI  - Revisiting human natural killer cell subset function revealed cytolytic
      CD56(dim)CD16+ NK cells as rapid producers of abundant IFN-gamma on activation.
AB  - The two major functions of human natural killer (NK) cells are conventionally
      associated with distinct cell subsets. Thus, cytolytic activity is mostly
      confined to the CD56(dim)CD16(+) subset, whereas cytokine production is generally
      assigned to CD56(bright)CD16(+/-) cells. In this study, we reevaluated the
      functional capabilities of these NK subsets with regard to the production of IFN
      gamma at different time points after cell triggering via NKp46 and NKp30
      activating receptors. Different from previous studies, cytokine production was
      also assessed at early intervals. We show that CD56(dim) NK cells produce IFN
      gamma already at 2 to 4 h, whereas no cytokine production is detected beyond 16
      h. In contrast, CD56(bright) cells release IFN-gamma only at late time intervals
      (>16 h after stimulation). The rapid IFN-gamma production by CD56(dim) NK cells
      is in line with the presence of IFN-gamma mRNA in freshly isolated cells. Rapid
      IFN-gamma production was also induced by combinations of IL-2, IL-12, and IL-15.
      Our data indicate that not only cytolytic activity but also early IFN-gamma
      production is a functional property of CD56(dim) NK cells. Thus, this subset can
      assure a rapid and comprehensive NK cell intervention during the early phases of
      innate responses.

PMID- 21187374
TI  - Potassium (K+) gradients serve as a mobile energy source in plant vascular
      tissues.
AB  - The essential mineral nutrient potassium (K(+)) is the most important inorganic
      cation for plants and is recognized as a limiting factor for crop yield and
      quality. Nonetheless, it is only partially understood how K(+) contributes to
      plant productivity. K(+) is used as a major active solute to maintain turgor and
      to drive irreversible and reversible changes in cell volume. K(+) also plays an
      important role in numerous metabolic processes, for example, by serving as an
      essential cofactor of enzymes. Here, we provide evidence for an additional,
      previously unrecognized role of K(+) in plant growth. By combining diverse
      experimental approaches with computational cell simulation, we show that K(+)
      circulating in the phloem serves as a decentralized energy storage that can be
      used to overcome local energy limitations. Posttranslational modification of the
      phloem-expressed Arabidopsis K(+) channel AKT2 taps this "potassium battery,"
      which then efficiently assists the plasma membrane H(+)-ATPase in energizing the
      transmembrane phloem (re)loading processes.

PMID- 21187375
TI  - Heterodimer of two bHLH-PAS proteins mediates juvenile hormone-induced gene
      expression.
AB  - Juvenile hormone (JH) plays crucial roles in many aspects of insect life. The
      Methoprene-tolerant (Met) gene product, a member of the bHLH-PAS family of
      transcriptional regulators, has been demonstrated to be a key component of the JH
      signaling pathway. However, the molecular function of Met in JH-induced signal
      transduction and gene regulation remains to be fully elucidated. Here we show
      that a transcriptional coactivator of the ecdysteroid receptor complex, FISC,
      acts as a functional partner of Met in mediating JH-induced gene expression. Met
      and FISC appear to use their PAS domains to form a dimer only in the presence of
      JH or JH analogs. In newly emerged adult female mosquitoes, expression of some JH
      responsive genes is considerably dampened when Met or FISC is depleted by RNAi.
      Met and FISC are found to be associated with the promoter of the early trypsin
      gene (AaET) when transcription of this gene is activated by JH. A juvenile
      hormone response element (JHRE) has been identified in the AaET upstream
      regulatory region and is bound in vitro by the Met-FISC complex present in the
      nuclear protein extracts of previtellogenic adult female mosquitoes. In addition,
      the Drosophila homologs of Met and FISC can also use this mosquito JHRE to
      activate gene transcription in response to JH in a cell transfection assay.
      Together, the evidence indicates that Met and FISC form a functional complex on
      the JHRE in the presence of JH and directly activate transcription of JH target
      genes.

PMID- 21187376
TI  - Adapting North American wheat production to climatic challenges, 1839-2009.
AB  - The Intergovernmental Panel on Climate Change projects that temperatures in the
      major grain-growing areas of North America will rise by 3-4  degrees C by 2100.
      Such abrupt changes will create major challenges, significantly altering the area
      suitable for wheat. The historical record offers insight into the capability of
      agriculture to adapt to climatic challenges. Using a new county-level dataset on
      wheat production and climate norms, we show that during the 19th and 20th
      centuries North American grain farmers pushed wheat production into environments
      once considered too arid, too variable, and too harsh to cultivate. As summary
      measures, the median annual precipitation norm of the 2007 distribution of North
      American wheat production was one-half that of the 1839 distribution, and the
      median annual temperature norm was 3.7  degrees C lower. This shift, which
      occurred mostly before 1929, required new biological technologies. The Green
      Revolution associated with the pioneering work of Norman Borlaug represented an
      important advance in this longer process of biological innovation. However, well
      before the Green Revolution, generations of North American farmers overcame
      significant climatic challenges.

PMID- 21187377
TI  - Vibrio cholerae anaerobic induction of virulence gene expression is controlled by
      thiol-based switches of virulence regulator AphB.
AB  - Bacterial pathogens have evolved sophisticated signal transduction systems to
      coordinately control the expression of virulence determinants. For example, the
      human pathogen Vibrio cholerae is able to respond to host environmental signals
      by activating transcriptional regulatory cascades. The host signals that
      stimulate V. cholerae virulence gene expression, however, are still poorly
      understood. Previous proteomic studies indicated that the ambient oxygen
      concentration plays a role in V. cholerae virulence gene expression. In this
      study, we found that under oxygen-limiting conditions, an environment similar to
      the intestines, V. cholerae virulence genes are highly expressed. We show that
      anaerobiosis enhances dimerization and activity of AphB, a transcriptional
      activator that is required for the expression of the key virulence regulator
      TcpP, which leads to the activation of virulence factor production. We further
      show that one of the three cysteine residues in AphB, C(235), is critical for
      oxygen responsiveness, as the AphB(C235S) mutant can activate virulence genes
      under aerobic conditions in vivo and can bind to tcpP promoters in the absence of
      reducing agents in vitro. Mass spectrometry analysis suggests that under aerobic
      conditions, AphB is modified at the C(235) residue. This modification is
      reversible between oxygen-rich aquatic environments and oxygen-limited human
      hosts, suggesting that V. cholerae may use a thiol-based switch mechanism to
      sense intestinal signals and activate virulence.

PMID- 21187378
TI  - Vitamin A-dependent transcriptional activation of the nuclear factor of activated
      T cells c1 (NFATc1) is critical for the development and survival of B1 cells.
AB  - B1 cells represent a distinct subset of B cells that produce most of the natural
      serum IgM and much of the gut IgA and function as an important component of early
      immune responses to pathogens. The development of B1 cells depends on the nuclear
      factor of activated T cells c1 (NFATc1), a transcription factor abundantly
      expressed by B1 cells but not by conventional B2 cells. However, the factors that
      regulate the expression of NFATc1 in B1 cells remain unknown. Here we show that a
      vitamin A-deficient diet results in reduction of NFATc1 expression in B1 cells
      and almost complete loss of the B1 cell compartment. As a consequence, vitamin A
      deficient mice have reduced serum IgM and are unable to mount T cell-independent
      antibody responses against bacterial antigens. We demonstrate that injection of
      all-trans retinoic acid induces the expression of NFATc1, particularly from the
      constitutive P2 promoter, and leads to the increase of the B1 cells. Thus, the
      retinoic acid-dependent pathway is critical for regulating NFATc1 expression and
      for maintenance of the natural memory B cell compartment.

PMID- 21187379
TI  - Adaptin-like protein TPLATE and clathrin recruitment during plant somatic
      cytokinesis occurs via two distinct pathways.
AB  - Plant cytokinesis deploys a transport system that centers cell plate-forming
      vesicles and fuses them to form a cell plate. Here we show that the adaptin-like
      protein TPLATE and clathrin light chain 2 (CLC2) are targeted to the expanding
      cell plate and to the equatorial subregion of the plasma membrane referred to as
      the cortical division zone (CDZ). Bimolecular fluorescence complementation and
      immunodetection indicates that TPLATE interacts with clathrin. Pharmacological
      tools as well as analysis of protein targeting in a mutant background affecting
      cell plate formation allowed to discriminate two recruitment pathways for TPLATE
      and CLC2. The cell plate recruitment pathway is dependent on phragmoplast
      microtubule organization and the formation and transport of secretory vesicles.
      The CDZ recruitment pathway, on the other hand, is activated at the end of
      cytokinesis and independent of trans-Golgi-derived vesicle trafficking. TPLATE
      and CLC2 do not accumulate at a narrow zone central of the CDZ. We have dubbed
      this subdomain the cortical division site and show that it corresponds precisely
      with the position where the cell plate merges with the parental wall. These data
      provide evidence that the plasma membrane is subject to localized endocytosis or
      membrane remodeling processes that are required for the fusion of the cell plate
      with a predefined region of the plasma membrane.

PMID- 21187380
TI  - Assembly of nonnative floras along elevational gradients explained by directional
      ecological filtering.
AB  - Nonnative species richness typically declines along environmental gradients such
      as elevation. It is usually assumed that this is because few invaders possess the
      necessary adaptations to succeed under extreme environmental conditions. Here, we
      show that nonnative plants reaching high elevations around the world are not
      highly specialized stress tolerators but species with broad climatic tolerances
      capable of growing across a wide elevational range. These results contrast with
      patterns for native species, and they can be explained by the unidirectional
      expansion of nonnative species from anthropogenic sources at low elevations and
      the progressive dropping out of species with narrow elevational amplitudes--a
      process that we call directional ecological filtering. Independent data confirm
      that climatic generalists have succeeded in colonizing the more extreme
      environments at higher elevations. These results suggest that invasion resistance
      is not conferred by extreme conditions at a particular site but determined by
      pathways of introduction of nonnative species. In the future, increased direct
      introduction of nonnative species with specialized ecophysiological adaptations
      to mountain environments could increase the risk of invasion. As well as
      providing a general explanation for gradients of nonnative species richness and
      the importance of traits such as phenotypic plasticity for many invasive species,
      the concept of directional ecological filtering is useful for understanding the
      initial assembly of some native floras at high elevations and latitudes.

PMID- 21187381
TI  - Behavioral consequences of dopamine deficiency in the Drosophila central nervous
      system.
AB  - The neuromodulatory function of dopamine (DA) is an inherent feature of nervous
      systems of all animals. To learn more about the function of neural DA in
      Drosophila, we generated mutant flies that lack tyrosine hydroxylase, and thus DA
      biosynthesis, selectively in the nervous system. We found that DA is absent or
      below detection limits in the adult brain of these flies. Despite this, they have
      a lifespan similar to WT flies. These mutants show reduced activity, extended
      sleep time, locomotor deficits that increase with age, and they are hypophagic.
      Whereas odor and electrical shock avoidance are not affected, aversive olfactory
      learning is abolished. Instead, DA-deficient flies have an apparently
      "masochistic" tendency to prefer the shock-associated odor 2 h after
      conditioning. Similarly, sugar preference is absent, whereas sugar stimulation of
      foreleg taste neurons induces normal proboscis extension. Feeding the DA
      precursor L-DOPA to adults substantially rescues the learning deficit as well as
      other impaired behaviors that were tested. DA-deficient flies are also defective
      in positive phototaxis, without alteration in visual perception and optomotor
      response. Surprisingly, visual tracking is largely maintained, and these mutants
      still possess an efficient spatial orientation memory. Our findings show that
      flies can perform complex brain functions in the absence of neural DA, whereas
      specific behaviors involving, in particular, arousal and choice require normal
      levels of this neuromodulator.

PMID- 21187382
TI  - Enhanced striatal cholinergic neuronal activity mediates L-DOPA-induced
      dyskinesia in parkinsonian mice.
AB  - Treatment of Parkinson disease (PD) with L-3,4-dihydroxyphenylalanine (L-DOPA)
      dramatically relieves associated motor deficits, but L-DOPA-induced dyskinesias
      (LID) limit the therapeutic benefit over time. Previous investigations have noted
      changes in striatal medium spiny neurons, including abnormal activation of
      extracellular signal-regulated kinase1/2 (ERK). Using two PD models, the
      traditional 6-hydroxydopamine toxic lesion and a genetic model with nigrostriatal
      dopaminergic deficits, we found that acute dopamine challenge induces ERK
      activation in medium spiny neurons in denervated striatum. After repeated L-DOPA
      treatment, however, ERK activation diminishes in medium spiny neurons and
      increases in striatal cholinergic interneurons. ERK activation leads to enhanced
      basal firing rate and stronger excitatory responses to dopamine in striatal
      cholinergic neurons. Pharmacological blockers of ERK activation inhibit L-DOPA
      induced changes in ERK phosphorylation, neuronal excitability, and the behavioral
      manifestation of LID. In addition, a muscarinic receptor antagonist reduces LID.
      These data indicate that increased dopamine sensitivity of striatal cholinergic
      neurons contributes to the expression of LID, which suggests novel therapeutic
      targets for LID.

PMID- 21187383
TI  - Pre- and postexposure protection against virulent anthrax infection in mice by
      humanized monoclonal antibodies to Bacillus anthracis capsule.
AB  - One of the two essential virulence factors of Bacillus anthracis is the poly
      gamma-D-glutamic acid (gammaDPGA) capsule. Five gammaDPGA-specific antibody
      antigen-binding fragments (Fabs) were generated from immunized chimpanzees. The
      two selected for further study, Fabs 11D and 4C, were both converted into full
      length IgG1 and IgG3 mAbs having human IgG1 or IgG3 constant regions. These two
      mAbs had similar binding affinities, in vitro opsonophagocytic activities, and in
      vivo efficacies, with the IgG1 and IgG3 subclasses reacting similarly. The mAbs
      bound to gammaDPGA specifically with estimated binding affinities (K(d)) of 35-70
      nM and effective affinities (effective K(d)) of 0.1-0.3 nM. The LD(50) in an
      opsonophagocytic bactericidal assay was ~10 ng/mL of 11D or 4C. A single 30-MUg
      dose of either mAb given to BALB/c mice 18 h before challenge conferred about 50%
      protection against a lethal intratracheal spore challenge by the virulent B.
      anthracis Ames strain. More importantly, either mAb given 8 h or 20 h after
      challenge provided significant protection against lethal infection. Thus, these
      anti-gammaDPGA mAbs should be useful, alone or in combination with antitoxin
      mAbs, for achieving a safe and efficacious postexposure therapy for anthrax.

PMID- 21187384
TI  - Phosphorylation of Grainy head by ERK is essential for wound-dependent
      regeneration but not for development of an epidermal barrier.
AB  - Grainy head (GRH) is a key transcription factor responsible for epidermal barrier
      formation and repair, whose function is highly conserved across diverse animal
      species. However, it is not known how GRH function is reactivated to repair
      differentiated epidermal barriers after wounding. Here, we show that GRH is
      directly regulated by extracellular signal-regulated kinase (ERK)
      phosphorylation, which is required for wound-dependent expression of GRH target
      genes in epidermal cells. Serine 91 is the principal residue in GRH that is
      phosphorylated by ERK. Although mutations of the ERK phosphorylation sites in GRH
      do not impair its DNA binding function, the ERK sites in GRH are required to
      activate Dopa decarboxylase (Ddc) and misshapen (msn) epidermal wound enhancers
      as well as functional regeneration of an epidermal barrier upon wounding. This
      result indicates that the phosphorylation sites are essential for damaged
      epidermal barrier repair. However, GRH with mutant ERK phosphorylation sites can
      still promote barrier formation during embryonic epidermal development,
      suggesting that ERK sites are dispensable for the GRH function in establishing
      epidermal barrier integrity. These results provide mechanistic insight into how
      tissue repair can be initiated by posttranslational modification of a key
      transcription factor that normally mediates the developmental generation of that
      tissue.

PMID- 21187385
TI  - Biglycan recruits utrophin to the sarcolemma and counters dystrophic pathology in
      mdx mice.
AB  - Duchenne muscular dystrophy (DMD) is caused by mutations in dystrophin and the
      subsequent disruption of the dystrophin-associated protein complex (DAPC).
      Utrophin is a dystrophin homolog expressed at high levels in developing muscle
      that is an attractive target for DMD therapy. Here we show that the extracellular
      matrix protein biglycan regulates utrophin expression in immature muscle and that
      recombinant human biglycan (rhBGN) increases utrophin expression in cultured
      myotubes. Systemically delivered rhBGN up-regulates utrophin at the sarcolemma
      and reduces muscle pathology in the mdx mouse model of DMD. RhBGN treatment also
      improves muscle function as judged by reduced susceptibility to eccentric
      contraction-induced injury. Utrophin is required for the rhBGN therapeutic
      effect. Several lines of evidence indicate that biglycan acts by recruiting
      utrophin protein to the muscle membrane. RhBGN is well tolerated in animals dosed
      for as long as 3 months. We propose that rhBGN could be a therapy for DMD.

PMID- 21187386
TI  - High-quality draft assemblies of mammalian genomes from massively parallel
      sequence data.
AB  - Massively parallel DNA sequencing technologies are revolutionizing genomics by
      making it possible to generate billions of relatively short (~100-base) sequence
      reads at very low cost. Whereas such data can be readily used for a wide range of
      biomedical applications, it has proven difficult to use them to generate high
      quality de novo genome assemblies of large, repeat-rich vertebrate genomes. To
      date, the genome assemblies generated from such data have fallen far short of
      those obtained with the older (but much more expensive) capillary-based
      sequencing approach. Here, we report the development of an algorithm for genome
      assembly, ALLPATHS-LG, and its application to massively parallel DNA sequence
      data from the human and mouse genomes, generated on the Illumina platform. The
      resulting draft genome assemblies have good accuracy, short-range contiguity,
      long-range connectivity, and coverage of the genome. In particular, the base
      accuracy is high (>=99.95%) and the scaffold sizes (N50 size = 11.5 Mb for human
      and 7.2 Mb for mouse) approach those obtained with capillary-based sequencing.
      The combination of improved sequencing technology and improved computational
      methods should now make it possible to increase dramatically the de novo
      sequencing of large genomes. The ALLPATHS-LG program is available at
      http://www.broadinstitute.org/science/programs/genome-biology/crd.

PMID- 21187387
TI  - Trk retrograde signaling requires persistent, Pincher-directed endosomes.
AB  - Target-derived neurotrophins use retrogradely transported Trk-signaling endosomes
      to promote survival and neuronal phenotype at the soma. Despite their critical
      role in neurotrophin signaling, the nature and molecular composition of these
      endosomes remain largely unknown, the result of an inability to specifically
      identify the retrograde signaling entity. Using EGF-bound nanoparticles and
      chimeric, EGF-binding TrkB receptors, we elucidate Trk-endosomal events involving
      their formation, processing, retrograde transport, and somal signaling in
      sympathetic neurons. By comparing retrograde endosomal signaling by Trk to the
      related but poorly neuromodulatory EGF-receptor, we find that Trk and EGF
      receptor endosomes are formed and processed by distinct mechanisms. Surprisingly,
      Trk and EGF-receptors are both retrogradely transported to the soma in
      multivesicular bodies. However, only the Trk-multivesicular bodies rely on
      Pincher-dependent macroendocytosis and processing. Retrograde signaling through
      Pincher-generated Trk-multivesicular bodies is distinctively refractory to signal
      termination by lysosomal processing, resulting in sustained somal signaling and
      neuronal gene expression.

PMID- 21187388
TI  - Vaccination inducing broad and improved cross protection against multiple
      subtypes of influenza A virus.
AB  - Development of an influenza vaccine that provides broadly cross-protective
      immunity has been a scientific challenge for more than half a century. This study
      presents an approach to overcome strain-specific protection by supplementing
      conventional vaccines with virus-like particles (VLPs) containing the conserved
      M2 protein (M2 VLPs) in the absence of adjuvants. We demonstrate that an
      inactivated influenza vaccine supplemented with M2 VLPs prevents disease symptoms
      without showing weight loss and confers complete cross protection against lethal
      challenge with heterologous influenza A viruses including the 2009 H1N1 pandemic
      virus as well as heterosubtypic H3N2 and H5N1 influenza viruses. Cross-protective
      immunity was long-lived, for more than 7 mo. Immune sera from mice immunized with
      M2 VLP supplemented vaccine transferred cross protection to naive mice. Dendritic
      and macrophage cells were found to be important for this cross protection
      mediated by immune sera. The results provide evidence that supplementation of
      seasonal influenza vaccines with M2 VLPs is a promising approach for overcoming
      the limitation of strain-specific protection by current vaccines and developing a
      universal influenza A vaccine.

PMID- 21187389
TI  - Protease activated receptor-1 inhibits the Maspin tumor-suppressor gene to
      determine the melanoma metastatic phenotype.
AB  - The thrombin receptor protease activated receptor-1 (PAR-1) is overexpressed in
      metastatic melanoma cell lines and tumor specimens. Previously, we demonstrated a
      significant reduction in tumor growth and experimental lung metastasis after PAR
      1 silencing via systemic delivery of siRNA encapsulated into nanoliposomes. Gene
      expression profiling identified a 40-fold increase in expression of Maspin in PAR
      1-silenced metastatic melanoma cell lines. Maspin promoter activity was
      significantly increased after PAR-1 silencing, suggesting that PAR1 negatively
      regulates Maspin at the transcriptional level. ChIP analyses revealed that PAR-1
      decreases binding of Ets-1 and c-Jun transcription factors to the Maspin
      promoter, both known to activate Maspin transcription. PAR-1 silencing did not
      affect Ets-1 or c-Jun expression; rather it resulted in increased expression of
      the chromatin remodeling complex CBP/p300, as well as decreased activity of the
      CBP/p300 inhibitor p38, resulting in increased binding of Ets-1 and c-Jun to the
      Maspin promoter and higher Maspin expression. Functionally, Maspin expression
      reduced the invasive capability of melanoma cells after PAR-1 silencing, which
      was abrogated after rescuing with PAR-1. Furthermore, tumor growth and
      experimental lung metastasis was significantly decreased after expressing Maspin
      in a metastatic melanoma cell line. Moreover, silencing Maspin in PAR-1-silenced
      cells reverted the inhibition of tumor growth and experimental lung metastasis.
      Herein, we demonstrate a mechanism by which PAR-1 negatively regulates the
      expression of the Maspin tumor-suppressor gene in the acquisition of the
      metastatic melanoma phenotype, thus attributing an alternative function to PAR-1
      other than coagulation.

PMID- 21187390
TI  - Illusory motion perception in blindsight.
AB  - Motion detection is typically spared in blindsight, which results from damage to
      the striate cortex (area V1) of the brain that is sufficient to eliminate
      conscious visual awareness and severely reduce sensitivity to luminance contrast,
      especially for high spatial and low temporal frequencies. Here we show that the
      discrimination of motion direction within cortically blind fields is not
      attributable to feature tracking (the detection of changes in position or shape),
      but is due instead to the detection of first-order motion energy (spatiotemporal
      changes in luminance). The key to this finding was a version of the line motion
      illusion entailing reverse-phi motion in which opposing motion directions are
      simultaneously cued by motion energy and changes in stimulus shape. In forced
      choice tests, a blindsighted test subject selected the direction cued by shape
      change when the stimulus was presented in his intact field, but reliably selected
      the direction cued by motion energy when the same stimulus was presented in his
      blind field, where relevant position information was either inaccessible or
      invalid. Motion energy has been characterized as objectless, so reliance on
      motion energy detection is consistent with impaired access to shape information
      in blindsight. The dissociation of motion direction by visual field (cortically
      blind vs. intact) provides evidence that two pathways from the retina to MT/V5
      (the cortical area specialized for motion perception) are functionally distinct:
      the retinogeniculate pathway through V1 is specialized for feature-based motion
      perception, whereas the retinocollicular pathway, which bypasses V1, is
      specialized for detecting motion energy.

PMID- 21187391
TI  - Ovariectomy disregulates osteoblast and osteoclast formation through the T-cell
      receptor CD40 ligand.
AB  - The bone loss induced by ovariectomy (ovx) has been linked to increased
      production of osteoclastogenic cytokines by bone marrow cells, including T cells
      and stromal cells (SCs). It is presently unknown whether regulatory interactions
      between these lineages contribute to the effects of ovx in bone, however. Here,
      we show that the T-cell costimulatory molecule CD40 ligand (CD40L) is required
      for ovx to expand SCs; promote osteoblast proliferation and differentiation;
      regulate the SC production of the osteoclastogenic factors macrophage colony
      stimulating factor, receptor activator of nuclear factor-kappaB ligand, and
      osteoprotegerin; and up-regulate osteoclast formation. CD40L is also required for
      ovx to activate T cells and stimulate their production of TNF. Accordingly, ovx
      fails to promote bone loss and increase bone resorption in mice depleted of T
      cells or lacking CD40L. Therefore, cross-talk between T cells and SCs mediated by
      CD40L plays a pivotal role in the disregulation of osteoblastogenesis and
      osteoclastogenesis induced by ovx.

PMID- 21187392
TI  - Expression and functional role of a transcribed noncoding RNA with an
      ultraconserved element in hepatocellular carcinoma.
AB  - Although expression of non-protein-coding RNA (ncRNA) can be altered in human
      cancers, their functional relevance is unknown. Ultraconserved regions are
      noncoding genomic segments that are 100% conserved across humans, mice, and rats.
      Conservation of gene sequences across species may indicate an essential
      functional role, and therefore we evaluated the expression of ultraconserved RNAs
      (ucRNA) in hepatocellular cancer (HCC). The global expression of ucRNAs was
      analyzed with a custom microarray. Expression was verified in cell lines by real
      time PCR or in tissues by in situ hybridization using tissue microarrays.
      Cellular ucRNA expression was modulated with siRNAs, and the effects on global
      gene expression and growth of human and murine HCC cells were evaluated. Fifty
      six ucRNAs were aberrantly expressed in HepG2 cells compared with nonmalignant
      hepatocytes. Among these ucRNAs, the greatest change was noted for ultraconserved
      element 338 (uc.338), which was dramatically increased in human HCC compared with
      noncancerous adjacent tissues. Although uc.338 is partially located within the
      poly(rC) binding protein 2 (PCBP2) gene, the transcribed ncRNA encoding uc.338 is
      expressed independently of PCBP2 and was cloned as a 590-bp RNA gene, termed
      TUC338. Functional gene annotation analysis indicated predominant effects on
      genes involved in cell growth. These effects were experimentally demonstrated in
      both human and murine cells. siRNA to TUC338 decreased both anchorage-dependent
      and anchorage-independent growth of HCC cells. These studies identify a critical
      role for TUC338 in regulation of transformed cell growth and of transcribed
      ultraconserved ncRNA as a unique class of genes involved in the pathobiology of
      HCC.

PMID- 21187393
TI  - Microfossils in calculus demonstrate consumption of plants and cooked foods in
      Neanderthal diets (Shanidar III, Iraq; Spy I and II, Belgium).
AB  - The nature and causes of the disappearance of Neanderthals and their apparent
      replacement by modern humans are subjects of considerable debate. Many
      researchers have proposed biologically or technologically mediated dietary
      differences between the two groups as one of the fundamental causes of
      Neanderthal disappearance. Some scenarios have focused on the apparent lack of
      plant foods in Neanderthal diets. Here we report direct evidence for Neanderthal
      consumption of a variety of plant foods, in the form of phytoliths and starch
      grains recovered from dental calculus of Neanderthal skeletons from Shanidar
      Cave, Iraq, and Spy Cave, Belgium. Some of the plants are typical of recent
      modern human diets, including date palms (Phoenix spp.), legumes, and grass seeds
      (Triticeae), whereas others are known to be edible but are not heavily used
      today. Many of the grass seed starches showed damage that is a distinctive marker
      of cooking. Our results indicate that in both warm eastern Mediterranean and cold
      northwestern European climates, and across their latitudinal range, Neanderthals
      made use of the diverse plant foods available in their local environment and
      transformed them into more easily digestible foodstuffs in part through cooking
      them, suggesting an overall sophistication in Neanderthal dietary regimes.

PMID- 21187394
TI  - Conserved endoplasmic reticulum-associated degradation system to eliminate
      mutated receptor-like kinases in Arabidopsis.
AB  - Endoplasmic reticulum (ER)-associated degradation (ERAD) is an integral part of
      the ER quality-control system that removes toxic misfolded proteins via
      ubiquitin/proteasome-mediated degradation. Most of our knowledge on ERAD comes
      from biochemical and genetic studies in yeast and mammalian cells. Although ERAD
      is known to operate in plant cells, little is known about its molecular
      components and its biochemical mechanism. A genetic screen for suppressors of the
      Arabidopsis bri1-9, a weak dwarf mutant caused by ER retention of a structurally
      defective yet biochemically competent brassinosteroid (BR) receptor BRI1,
      resulted in identification of the EMS-mutagenized bri1 suppressor 5 (EBS5) gene
      that encodes an Arabidopsis homolog of the yeast Hrd3/mammalian Sel1L protein
      known to be involved in ERAD. Loss-of-function ebs5 mutations block the ERAD of
      bri1-9 and bri1-5, another ER-retained BR receptor. We showed that EBS5
      complemented the ERAD defect of the yeast Deltahrd3 mutant and interacted with
      the two mutated BR receptors in plant cells. Using a reverse genetic approach, we
      discovered that two Arabidopsis homologs of the yeast/mammalian Hrd1, an ER
      membrane-localized ubiquitin ligase, function redundantly in the ERAD of bri1-9.
      Together, our results revealed functional roles of two conserved ERAD components
      in degrading mutated/misfolded receptor-like kinases in Arabidopsis.

PMID- 21187395
TI  - E2f binding-deficient Rb1 protein suppresses prostate tumor progression in vivo.
AB  - Mutational inactivation of the RB1 tumor suppressor gene initiates retinoblastoma
      and other human cancers. RB1 protein (pRb) restrains cell proliferation by
      binding E2f transcription factors and repressing the expression of cell cycle
      target genes. It is presumed that loss of pRb/E2f interaction accounts for tumor
      initiation, but this has not been directly tested. RB1 mutation is a late event
      in other human cancers, suggesting a role in tumor progression as well as
      initiation. It is currently unknown whether RB1 mutation drives tumor progression
      and, if so, whether loss of pRb/E2f interaction is responsible. We have
      characterized tumorigenesis in mice expressing a mutant pRb that is specifically
      deficient in binding E2f. In endocrine tissue, the mutant pRb has no detectable
      effect on tumorigenesis. In contrast, it significantly delays progression to
      invasive and lethal prostate cancer. Tumor delay is associated with induction of
      a senescence response. We conclude that the pRb/E2f interaction is critical for
      preventing tumor initiation, but that pRb can use additional context-dependent
      mechanisms to restrain tumor progression.

PMID- 21187396
TI  - Stromal retinoic acid receptor beta promotes mammary gland tumorigenesis.
AB  - Retinoic acid is a potent differentiation and antiproliferative agent of breast
      cancer cells, and one of its receptors, retinoic acid receptor beta (RARbeta),
      has been proposed to act as a tumor suppressor. In contrast, we report herein
      that inactivation of Rarb in the mouse results in a protective effect against
      ErbB2-induced mammary gland tumorigenesis. Strikingly, tissue recombination
      experiments indicate that the presence of Rarb in the stromal compartment is
      essential for the growth of mammary carcinoma. Ablation of Rarb leads to a
      remodeling of the stroma during tumor progression that includes a decrease in
      angiogenesis, in the recruitment of inflammatory cells, and in the number
      myofibroblasts. In agreement with this finding, we observed that a markedly
      reduced expression of chemokine (C-X-C motif) ligand 12 (Cxcl12) in the stroma of
      Rarb-null mice is accompanied by a decrease in the CXCL12/chemokine C-X-C
      receptor 4 (CXCR4)/ErbB2 signaling axis in the tumors. Relevance to the human
      disease is underlined by the finding that gene-expression profiling of the Rarb
      deficient mammary stromal compartment identified an ortholog RARbeta signature in
      human microdissected breast tissues that differentiates tumor from normal stroma.
      Our study thus implicates RARbeta in promoting tumorigenesis and suggests that
      retinoid-based approaches for the prevention and treatment of breast cancer
      should be redesigned.

PMID- 21187397
TI  - Nanoparticle-mediated delivery of siRNA targeting Parp1 extends survival of mice
      bearing tumors derived from Brca1-deficient ovarian cancer cells.
AB  - Inhibition of the DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP1) with
      small molecules has been shown to be an effective treatment for ovarian cancer
      with BRCA mutations. Here, we report the in vivo administration of siRNA to Parp1
      in mouse models of ovarian cancer. A unique member of the lipid-like materials
      known as lipidoids is shown to deliver siRNA to disseminated murine ovarian
      carcinoma allograft tumors following intraperitoneal (i.p.) injection. siParp1
      inhibits cell growth, primarily by induction of apoptosis, in Brca1-deficient
      cells both in vitro and in vivo. Additionally, the treatment extends the survival
      of mice bearing tumors derived from Brca1-deficient ovarian cancer cells but not
      from Brca1 wild-type cells, confirming the proposed mechanism of synthetic
      lethality. Because there are 17 members of the Parp family, the inherent
      complementarity of RNA affords a high level of specificity for therapeutically
      addressing Parp1 in the context of impaired homologous recombination.

PMID- 21187398
TI  - Unitary response of mouse olfactory receptor neurons.
AB  - The sense of smell begins with odorant molecules binding to membrane receptors on
      the cilia of olfactory receptor neurons (ORNs), thereby activating a G protein,
      G(olf), and the downstream effector enzyme, an adenylyl cyclase (ACIII).
      Recently, we have found in amphibian ORNs that an odorant-binding event has a low
      probability of activating sensory transduction at all; even when successful, the
      resulting unitary response apparently involves a single active Galpha(olf)-ACIII
      molecular complex. This low amplification is in contrast to rod phototransduction
      in vision, the best-quantified G-protein signaling pathway, where each
      photoisomerized rhodopsin molecule is well known to produce substantial
      amplification by activating many G-protein, and hence effector-enzyme, molecules.
      We have now carried out similar experiments on mouse ORNs, which offer,
      additionally, the advantage of genetics. Indeed, we found the same low
      probability of transduction, based on the unitary olfactory response having a
      fairly constant amplitude and similar kinetics across different odorants and
      randomly encountered ORNs. Also, consistent with our picture, the unitary
      response of Galpha(olf)(+/-) ORNs was similar to WT in amplitude, although their
      Galpha(olf)-protein expression was only half of normal. Finally, from the action
      potential firing, we estimated that <=19 odorant-binding events successfully
      triggering transduction in a WT mouse ORN will lead to signaling to the brain.

PMID- 21187400
TI  - Na,K-ATPase alpha4 isoform is essential for sperm fertility.
AB  - Regulation of ion balance in spermatozoa has been shown to be essential for sperm
      motility and fertility. Control of intracellular ion levels requires the function
      of distinct ion-transport mechanisms at the cell plasma membrane. Active Na(+)
      and K(+) exchange in sperm is under the control of the Na,K-ATPase. Two molecular
      variants of the catalytic subunit of the Na,K-ATPase, alpha1 and alpha4, coexist
      in sperm. These isoforms exhibit different biochemical properties; however, their
      function in sperm fertility is unknown. In this work, we show that Na,K-ATPase
      alpha4 is essential for sperm fertility. Knockout male mice lacking alpha4 are
      completely sterile and spermatozoa from these mice are unable of fertilizing eggs
      in vitro. Furthermore, alpha4 deletion results in severe reduction in sperm
      motility and hyperactivation typical of sperm capacitation. In addition, absence
      of alpha4 causes a characteristic bend in the sperm flagellum, indicative of
      abnormal sperm ion regulation. Accordingly, alpha4-null sperm present increased
      intracellular Na(+) and cell plasma membrane depolarization. These results are
      unique in demonstrating the absolute requirement of alpha4 for sperm fertility.
      Moreover, the inability of alpha1 to compensate for alpha4 suggests that alpha4
      is the Na,K-ATPase-alpha isoform directly involved in sperm fertility. Our
      findings show alpha4 as an attractive target for male contraception and open the
      possibility for the potential use of this Na,K-ATPase isoform as a biomarker for
      male fertility.

PMID- 21187399
TI  - Genetic susceptibility to systemic lupus erythematosus protects against cerebral
      malaria in mice.
AB  - Plasmodium falciparum has exerted tremendous selective pressure on genes that
      improve survival in severe malarial infections. Systemic lupus erythematosus
      (SLE) is an autoimmune disease that is six to eight times more prevalent in women
      of African descent than in women of European descent. Here we provide evidence
      that a genetic susceptibility to SLE protects against cerebral malaria. Mice that
      are prone to SLE because of a deficiency in FcgammaRIIB or overexpression of Toll
      like receptor 7 are protected from death caused by cerebral malaria. Protection
      appears to be by immune mechanisms that allow SLE-prone mice better to control
      their overall inflammatory responses to parasite infections. These findings
      suggest that the high prevalence of SLE in women of African descent living
      outside of Africa may result from the inheritance of genes that are beneficial in
      the immune control of cerebral malaria but that, in the absence of malaria,
      contribute to autoimmune disease.

PMID- 21187401
TI  - Identification of a gain-of-function mutation in a Golgi P-type ATPase that
      enhances Mn2+ efflux and protects against toxicity.
AB  - P-type ATPases transport a wide array of ions, regulate diverse cellular
      processes, and are implicated in a number of human diseases. However, mechanisms
      that increase ion transport by these ubiquitous proteins are not known. SPCA1 is
      a P-type pump that transports Mn(2+) from the cytosol into the Golgi. We
      developed an intra-Golgi Mn(2+) sensor and used it to screen for mutations
      introduced in SPCA1, on the basis of its predicted structure, which could
      increase its Mn(2+) pumping activity. Remarkably, a point mutation (Q747A)
      predicted to increase the size of its ion permeation cavity enhanced the sensor
      response and a compensatory mutation restoring the cavity to its original size
      abolished this effect. In vivo and in vitro Mn(2+) transport assays confirmed the
      hyperactivity of SPCA1-Q747A. Furthermore, increasing Golgi Mn(2+) transport by
      expression of SPCA1-Q747A increased cell viability upon Mn(2+) exposure,
      supporting the therapeutic potential of increased Mn(2+) uptake by the Golgi in
      the management of Mn(2+)-induced neurotoxicity.

PMID- 21187402
TI  - Apoptosis signal-regulating kinase 1 and cyclin D1 compose a positive feedback
      loop contributing to tumor growth in gastric cancer.
AB  - Mitogen-activated protein kinase (MAPK) pathways regulate multiple cellular
      functions and are highly active in many types of human cancers. Apoptosis signal
      regulating kinase 1 (ASK1) is an upstream MAPK involved in apoptosis,
      inflammation, and carcinogenesis. This study investigated the role of ASK1 in the
      development of gastric cancer. In human gastric cancer specimens, we observed
      increased ASK1 expression, compared to nontumor epithelium. Using a chemically
      induced murine gastric tumorigenesis model, we observed increased tumor ASK1
      expression, and ASK1 knockout mice had both fewer and smaller tumors than wild
      type (WT) mice. ASK1 siRNA inhibited cell proliferation through the accumulation
      of cells in G1 phase of the cell cycle, and reduced cyclin D1 expression in
      gastric cancer cells, whereas these effects were uncommon in other cancer cells.
      ASK1 overexpression induced the transcription of cyclin D1, through AP-1
      activation, and ASK1 levels were regulated by cyclin D1, via the Rb-E2F pathway.
      Exogenous ASK1 induced cyclin D1 expression, followed by elevated expression of
      endogenous ASK1. These results indicate an autoregulatory mechanism of ASK1 in
      the development of gastric cancer. Targeting this positive feedback loop, ASK1
      may present a potential therapeutic target for the treatment of advanced gastric
      cancer.

PMID- 21187403
TI  - Arc-dependent synapse-specific homeostatic plasticity.
AB  - Both theoretical and experimental research has indicated that the synaptic
      strength between neurons in a network needs to be properly fine-tuned and
      controlled by homeostatic mechanisms to ensure proper network function. One such
      mechanism that has been extensively characterized is synaptic homeostatic
      plasticity or global synaptic scaling. This mechanism refers to the bidirectional
      ability of all synapses impinging on a neuron to actively compensate for changes
      in the neuron's overall excitability. Here, using a combination of
      electrophysiological, two-photon glutamate uncaging and imaging methods, we show
      that mature individual synapses, independent of neighboring synapses, have the
      ability to autonomously sense their level of activity and actively compensate for
      it in a homeostatic-like fashion. This synapse-specific homeostatic plasticity,
      similar to global synaptic plasticity, requires the immediate early gene Arc.
      Together, our results document an extra level of regulation of synaptic function
      that bears important computational consequences on information storage in the
      brain.

PMID- 21187404
TI  - High-precision radiocarbon dating shows recent and rapid initial human
      colonization of East Polynesia.
AB  - The 15 archipelagos of East Polynesia, including New Zealand, Hawaii, and Rapa
      Nui, were the last habitable places on earth colonized by prehistoric humans. The
      timing and pattern of this colonization event has been poorly resolved, with
      chronologies varying by >1000 y, precluding understanding of cultural change and
      ecological impacts on these pristine ecosystems. In a meta-analysis of 1,434
      radiocarbon dates from the region, reliable short-lived samples reveal that the
      colonization of East Polynesia occurred in two distinct phases: earliest in the
      Society Islands A.D. ~1025-1120, four centuries later than previously assumed;
      then after 70-265 y, dispersal continued in one major pulse to all remaining
      islands A.D. ~1190-1290. We show that previously supported longer chronologies
      have relied upon radiocarbon-dated materials with large sources of error, making
      them unsuitable for precise dating of recent events. Our empirically based and
      dramatically shortened chronology for the colonization of East Polynesia resolves
      longstanding paradoxes and offers a robust explanation for the remarkable
      uniformity of East Polynesian culture, human biology, and language. Models of
      human colonization, ecological change and historical linguistics for the region
      now require substantial revision.

PMID- 21187405
TI  - Mechanism of tripartite RNA genome packaging in Rift Valley fever virus.
AB  - The Bunyaviridae family includes pathogens of medical and veterinary importance.
      Rift Valley fever virus (RVFV), a member in the Phlebovirus genus of the family
      Bunyaviridae, is endemic to sub-Saharan Africa and causes a mosquito-borne
      disease in ruminants and humans. Viruses in the family Bunyaviridae carry a
      tripartite, single-stranded, negative-sense RNA genome composed of L, M, and S
      RNAs. Little is known about how the three genomic RNA segments are copackaged to
      generate infectious bunyaviruses. We explored the mechanism that governs the
      copackaging of the three genomic RNAs into RVFV particles. The expression of
      viral structural proteins along with replicating S and M RNAs resulted in the
      copackaging of both RNAs into RVFV-like particles, while replacing M RNA with M1
      RNA, lacking a part of the M RNA 5' UTR, abrogated the RNA copackaging. L RNA was
      efficiently packaged into virus particles released from cells supporting the
      replication of L, M, and S RNAs, and replacing M RNA with M1 RNA abolished the
      packaging of L RNA. Detailed analyses using various combinations of replicating
      viral RNAs suggest that M RNA alone or a coordinated function of M and S RNAs
      exerted efficient L RNA packaging either directly or indirectly. Collectively,
      these data are consistent with the possibility that specific intermolecular
      interactions among the three viral RNAs drive the copackaging of these RNAs to
      produce infectious RVFV.

PMID- 21187406
TI  - Sorting receptor Rer1 controls surface expression of muscle acetylcholine
      receptors by ER retention of unassembled alpha-subunits.
AB  - The nicotinic acetylcholine receptor of skeletal muscle is composed of five
      subunits that are assembled in a stepwise manner. Quality control mechanisms
      ensure that only fully assembled receptors reach the cell surface. Here, we show
      that Rer1, a putative Golgi-ER retrieval receptor, is involved in the biogenesis
      of acetylcholine receptors. Rer1 is expressed in the early secretory pathway in
      the myoblast line C2C12 and in mouse skeletal muscle, and up-regulated during
      myogenesis. Upon down-regulation of Rer1 in C2C12 cells, unassembled
      acetylcholine receptor alpha-subunits escape from the ER and are transported to
      the plasma membrane and lysosomes, where they are degraded. As a result, the
      amount of fully assembled receptor at the cell surface is reduced. In vivo Rer1
      knockdown and genetic inactivation of one Rer1 allele lead to significantly
      smaller neuromuscular junctions in mice. Our data show that Rer1 is a
      functionally important unique factor that controls surface expression of muscle
      acetylcholine receptors by localizing unassembled alpha-subunits to the early
      secretory pathway.

PMID- 21187407
TI  - Beta Ca2+/CaM-dependent kinase type II triggers upregulation of GluA1 to
      coordinate adaptation to synaptic inactivity in hippocampal neurons.
AB  - Prolonged AMPA-receptor blockade in hippocampal neuron cultures leads to both an
      increased expression of GluA1 postsynaptically and an increase in vesicle pool
      size and turnover rate presynaptically, adaptive changes that extend beyond
      simple synaptic scaling. As a molecular correlate, expression of the beta
      Ca(2+)/CaM-dependent kinase type II (betaCaMKII) is increased in response to
      synaptic inactivity. Here we set out to clarify the role of betaCaMKII in the
      various manifestations of adaptation. Knockdown of betaCaMKII by lentiviral
      mediated expression of shRNA prevented the synaptic inactivity-induced increase
      in GluA1, as did treatment with the CaM kinase inhibitor KN-93, but not the
      inactive analog KN-92. These results demonstrate that, spurred by AMPA-receptor
      blockade, up-regulation of betaCaMKII promotes increased GluA1 expression.
      Indeed, transfection of betaCaMKII, but not a kinase-dead mutant, increased GluA1
      expression on dendrites and elevated vesicle turnover (Syt-Ab uptake), mimicking
      the effect of synaptic inactivity on both sides of the synapse. In cells with
      elevated betaCaMKII, relief of synaptic-activity blockade uncovered an increase
      in the frequency of miniature excitatory postsynaptic currents that could be
      rapidly and fully suppressed by PhTx blockade of GluA1 receptors. This increased
      mini frequency involved a genuine presynaptic enhancement, not merely an
      increased abundance of synapses. This finding suggests that Ca(2+) flux through
      GluA1 receptors may trigger the acute release of a retrograde messenger. Taken
      together, our results indicate that synaptic inactivity-induced increases in
      betaCaMKII expression set in motion a series of events that culminate in
      coordinated pre- and postsynaptic adaptations in synaptic transmission.

PMID- 21187408
TI  - Egr1 mediates p53-independent c-Myc-induced apoptosis via a noncanonical ARF
      dependent transcriptional mechanism.
AB  - c-Myc is frequently deregulated in human cancers. Although deregulated c-Myc
      leads to tumor growth, it also triggers apoptosis in partnership with tumor
      suppressors such as ARF and p53. Apoptosis induced by c-Myc is a critical fail
      safe mechanism for the cell to protect against unrestrained proliferation.
      Despite the plethora of information on c-Myc, the molecular mechanism of how c
      Myc induces both transformation and apoptosis is unclear. Oncogenic c-Myc can
      indirectly induce the expression of the tumor suppressor ARF, which leads to
      apoptosis through the stabilization of p53, but both c-Myc and ARF have apoptotic
      activities that are independent of p53. In cells without p53, ARF directly binds
      to c-Myc protein and inhibits c-Myc-induced hyperproliferation and transformation
      with a concomitant inhibition of canonical c-Myc target gene induction. However,
      ARF is an essential cofactor for p53-independent c-Myc-induced apoptosis. Here we
      show that ARF is necessary for c-Myc to drive transcription of a unique
      noncanonical target gene, Egr1. In contrast, c-Myc induces another family member,
      Egr2, through a canonical mechanism that is inhibited by ARF. We further
      demonstrate that Egr1 is essential for p53-independent c-Myc-induced apoptosis,
      but not ARF-independent c-Myc-induced apoptosis. Therefore, ARF binding switches
      the inherent activity of c-Myc from a proliferative to apoptotic protein without
      p53 through a unique noncanonical transcriptional mechanism. These findings also
      provide evidence that cofactors can differentially regulate specific
      transcriptional programs of c-Myc leading to different biological outcomes.

PMID- 21187409
TI  - B cell homeostasis and plasma cell homing controlled by Kruppel-like factor 2.
AB  - Kruppel-like factor 2 (KLF2) controls T lymphocyte egress from lymphoid organs by
      regulating sphingosin-1 phosphate receptor 1 (S1Pr1). Here we show that this is
      not the case for B cells. Instead, KLF2 controls homeostasis of B cells in
      peripheral lymphatic organs and homing of plasma cells to the bone marrow,
      presumably by controlling the expression of beta(7)-integrin. In mice with a B
      cell-specific deletion of KLF2, S1Pr1 expression on B cells was only slightly
      affected. Accordingly, all splenic B cell subsets including B1 cells were
      present, but their numbers were increased with a clear bias for marginal zone
      (MZ) B cells. In contrast, fewer peyers patches harboring fewer B cells were
      found, and fewer B1 cells in the peritoneal cavity as well as recirculating B
      cells in the bone marrow were detected. Upon thymus-dependent immunization, IgG
      titers were diminished, and antigen-specific plasma cells were absent in the bone
      marrow, although numbers of antigen-specific splenic plasmablasts were normal.
      KLF2 plays also a role in determining the identity of follicular B cells, as KLF2
      deficient follicular B cells showed calcium responses similar to those of MZ B
      cells and failed to down-regulate MZ B cell signature genes, such as CD21 and
      CXCR7.

PMID- 21187410
TI  - Kruppel-like factor 2 (KLF2) regulates B-cell reactivity, subset differentiation,
      and trafficking molecule expression.
AB  - The transcription factor Kruppel-like factor 2 (KLF2) is critical for normal
      trafficking of T lymphocytes, but its role in B cells is unclear. We report that
      B cell-specific KLF2 deficiency leads to decreased expression of the trafficking
      molecules CD62L and beta7-integrin, yet expression of sphingosine-1 phosphate
      receptor 1 (which is a critical target of KLF2 in T cells) was, unexpectedly,
      minimally altered. Unexpectedly, Klf2 deletion led to a drastic reduction in the
      B1 B-cell pool and a substantial increase in transitional and marginal zone B
      cell numbers. In addition, we observed that KLF2-deficient B cells showed
      increased apoptosis and impaired proliferation after B-cell receptor cross
      linking. Gene expression analysis indicated that KLF2-deficient follicular B
      cells display numerous characteristics shared by normal marginal zone B cells,
      including reduced expression of several signaling molecules that may contribute
      to defective activation of these cells. Hence, our data indicate that KLF2 plays
      a critical role in dictating normal subset differentiation and functional
      reactivity of mature B cells.

PMID- 21187411
TI  - Misfolded proteins impose a dosage-dependent fitness cost and trigger a cytosolic
      unfolded protein response in yeast.
AB  - Evolving lineages face a constant intracellular threat: most new coding sequence
      mutations destabilize the folding of the encoded protein. Misfolded proteins form
      insoluble aggregates and are hypothesized to be intrinsically cytotoxic. Here, we
      experimentally isolate a fitness cost caused by toxicity of misfolded proteins.
      We exclude other costs of protein misfolding, such as loss of functional protein
      or attenuation of growth-limiting protein synthesis resources, by comparing
      growth rates of budding yeast expressing folded or misfolded variants of a
      gratuitous protein, YFP, at equal levels. We quantify a fitness cost that
      increases with misfolded protein abundance, up to as much as a 3.2% growth rate
      reduction when misfolded YFP represents less than 0.1% of total cellular protein.
      Comparable experiments on variants of the yeast gene orotidine-5'-phosphate
      decarboxylase (URA3) produce similar results. Quantitative proteomic measurements
      reveal that, within the cell, misfolded YFP induces coordinated synthesis of
      interacting cytosolic chaperone proteins in the absence of a wider stress
      response, providing evidence for an evolved modular response to misfolded
      proteins in the cytosol. These results underscore the distinct and evolutionarily
      relevant molecular threat of protein misfolding, independent of protein function.
      Assuming that most misfolded proteins impose similar costs, yeast cells express
      almost all proteins at steady-state levels sufficient to expose their encoding
      genes to selection against misfolding, lending credibility to the recent
      suggestion that such selection imposes a global constraint on molecular
      evolution.

PMID- 21187412
TI  - Critical role of aquaporin-4 (AQP4) in astrocytic Ca2+ signaling events elicited
      by cerebral edema.
AB  - Aquaporin-4 (AQP4) is a primary influx route for water during brain edema
      formation. Here, we provide evidence that brain swelling triggers Ca(2+)
      signaling in astrocytes and that deletion of the Aqp4 gene markedly interferes
      with these events. Using in vivo two-photon imaging, we show that hypoosmotic
      stress (20% reduction in osmolarity) initiates astrocytic Ca(2+) spikes and that
      deletion of Aqp4 reduces these signals. The Ca(2+) signals are partly dependent
      on activation of P2 purinergic receptors, which was judged from the effects of
      appropriate antagonists applied to cortical slices. Supporting the involvement of
      purinergic signaling, osmotic stress was found to induce ATP release from
      cultured astrocytes in an AQP4-dependent manner. Our results suggest that AQP4
      not only serves as an influx route for water but also is critical for initiating
      downstream signaling events that may affect and potentially exacerbate the
      pathological outcome in clinical conditions associated with brain edema.

PMID- 21187413
TI  - DRD2/AKT1 interaction on D2 c-AMP independent signaling, attentional processing,
      and response to olanzapine treatment in schizophrenia.
AB  - The D2/AKT1/GSK-3beta signaling pathway has been involved in the downstream
      intracellular effects of dopamine, in the pathophysiology of cognitive deficits
      and related brain activity in schizophrenia, as well as in response to treatment
      with antipsychotics. Polymorphisms in the D2 (DRD2 rs1076560) and AKT1 (AKT1
      rs1130233) genes have been associated with their respective protein expression
      and with higher-order cognition and brain function, including attention. Given
      the strong potential for their relationship, we investigated the interaction of
      these polymorphisms on multiple molecular and in vivo phenotypes associated with
      this signaling pathway. We measured AKT1 and GSK-3beta proteins and
      phosphorylation in human peripheral blood mononuclear cells, functional MRI
      cingulate response during attentional control, behavioral accuracy during
      sustained attention, and response to 8 wk of treatment with olanzapine in a total
      of 190 healthy subjects and 66 patients with schizophrenia. In healthy subjects,
      we found that the interaction between the T allele of DRD2 rs1076560 and the A
      allele of AKT1 rs1130233 was associated with reduced AKT1 protein levels and
      reduced phosphorylation of GSK-3beta, as well as with altered cingulate response
      and reduced behavioral accuracy during attentional processing. On the other hand,
      interaction of these two alleles was associated with greater improvement of
      Positive and Negative Syndrome Scale scores in patients with schizophrenia after
      treatment with olanzapine. The present results indicate that these functional
      polymorphisms are epistatically associated with multiple phenotypes of relevance
      to schizophrenia. Our results also lend support to further investigation of this
      downstream molecular pathway in the etiology and treatment of this disorder.

PMID- 21187414
TI  - Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in
      a mouse model.
AB  - Preeclampsia is a relatively common pregnancy-related disorder. Both maternal and
      fetal lives will be endangered if it proceeds unabated. Recently, the placenta
      derived anti-angiogenic factors, such as soluble fms-like tyrosine kinase-1
      (sFLT1) and soluble endoglin (sENG), have attracted attention in the progression
      of preeclampsia. Here, we established a unique experimental model to test the
      role of sFLT1 in preeclampsia using a lentiviral vector-mediated placenta
      specific expression system. The model mice showed hypertension and proteinuria
      during pregnancy, and the symptoms regressed after parturition. Intrauterine
      growth restriction was also observed. We further showed that pravastatin induced
      the VEGF-like angiogenic factor placental growth factor (PGF) and ameliorated the
      symptoms. We conclude that our experimental preeclamptic murine model phenocopies
      the human case, and the model identifies low-dose statins and PGF as candidates
      for preeclampsia treatment.

PMID- 21187415
TI  - Holin triggering in real time.
AB  - During lambda infections, the holin S105 accumulates harmlessly in the membrane
      until, at an allele-specific time, suddenly triggering to form irregular holes of
      unprecedented size (>300 nm), releasing the endolysin from the cytoplasm,
      resulting in lysis within seconds. Here we used a functional S105-GFP chimera and
      real-time deconvolution fluorescence microscopy to show that the S105-GFP fusion
      accumulated in a uniformly distributed fashion, until suddenly, within 1 min, it
      formed aggregates, or rafts, at the time of lethal triggering. Moreover, the
      isogenic fusion to a nonlethal S105 mutant remained uniformly distributed,
      whereas a fusion to an early-lysing mutant showed early triggering and early raft
      formation. Protein accumulation rates of the WT, early, and nonlethal alleles
      were identical. Fluorescence recovery after photobleaching (FRAP) revealed that
      the nonlethal mutant and untriggered WT hybrids were highly mobile in the
      membrane, whereas the WT raft was essentially immobile. Finally, an antiholin
      allele, S105(DeltaTMD1)-mcherryfp, in the product of which the S105 sequence
      deleted for the first transmembrane domain was fused to mCherryFP. This hybrid
      retained full antiholin activity, in that it blocked lethal hole formation by the
      S105-GFP fusion, accumulated uniformly throughout the host membrane and prevented
      the S105-GFP protein from forming rafts. These findings suggest that phage lysis
      occurs when the holin reaches a critical concentration and nucleates to form
      rafts, analogous to the initiation of purple membrane formation after the
      induction of bacteriorhodopsin in halobacteria. This model for holin function may
      be relevant for processes in mammalian cells, including the release of
      nonenveloped viruses and apoptosis.

PMID- 21187416
TI  - Ancient watercourses and biogeography of the Sahara explain the peopling of the
      desert.
AB  - Evidence increasingly suggests that sub-Saharan Africa is at the center of human
      evolution and understanding routes of dispersal "out of Africa" is thus becoming
      increasingly important. The Sahara Desert is considered by many to be an obstacle
      to these dispersals and a Nile corridor route has been proposed to cross it. Here
      we provide evidence that the Sahara was not an effective barrier and indicate how
      both animals and humans populated it during past humid phases. Analysis of the
      zoogeography of the Sahara shows that more animals crossed via this route than
      used the Nile corridor. Furthermore, many of these species are aquatic. This
      dispersal was possible because during the Holocene humid period the region
      contained a series of linked lakes, rivers, and inland deltas comprising a large
      interlinked waterway, channeling water and animals into and across the Sahara,
      thus facilitating these dispersals. This system was last active in the early
      Holocene when many species appear to have occupied the entire Sahara. However,
      species that require deep water did not reach northern regions because of weak
      hydrological connections. Human dispersals were influenced by this distribution;
      Nilo-Saharan speakers hunting aquatic fauna with barbed bone points occupied the
      southern Sahara, while people hunting Savannah fauna with the bow and arrow
      spread southward. The dating of lacustrine sediments show that the "green Sahara"
      also existed during the last interglacial (~125 ka) and provided green corridors
      that could have formed dispersal routes at a likely time for the migration of
      modern humans out of Africa.

PMID- 21187417
TI  - RNA polymerase and transcription elongation factor Spt4/5 complex structure.
AB  - Spt4/5 in archaea and eukaryote and its bacterial homolog NusG is the only
      elongation factor conserved in all three domains of life and plays many key roles
      in cotranscriptional regulation and in recruiting other factors to the elongating
      RNA polymerase. Here, we present the crystal structure of Spt4/5 as well as the
      structure of RNA polymerase-Spt4/5 complex using cryoelectron microscopy
      reconstruction and single particle analysis. The Spt4/5 binds in the middle of
      RNA polymerase claw and encloses the DNA, reminiscent of the DNA polymerase clamp
      and ring helicases. The transcription elongation complex model reveals that the
      Spt4/5 is an upstream DNA holder and contacts the nontemplate DNA in the
      transcription bubble. These structures reveal that the cellular RNA polymerases
      also use a strategy of encircling DNA to enhance its processivity as commonly
      observed for many nucleic acid processing enzymes including DNA polymerases and
      helicases.

PMID- 21187418
TI  - Structure-guided reprogramming of serine recombinase DNA sequence specificity.
AB  - Routine manipulation of cellular genomes is contingent upon the development of
      proteins and enzymes with programmable DNA sequence specificity. Here we describe
      the structure-guided reprogramming of the DNA sequence specificity of the
      invertase Gin from bacteriophage Mu and Tn3 resolvase from Escherichia coli.
      Structure-guided and comparative sequence analyses were used to predict a network
      of amino acid residues that mediate resolvase and invertase DNA sequence
      specificity. Using saturation mutagenesis and iterative rounds of positive
      antibiotic selection, we identified extensively redesigned and highly convergent
      resolvase and invertase populations in the context of engineered zinc-finger
      recombinase (ZFR) fusion proteins. Reprogrammed variants selectively catalyzed
      recombination of nonnative DNA sequences > 10,000-fold more effectively than
      their parental enzymes. Alanine-scanning mutagenesis revealed the molecular basis
      of resolvase and invertase DNA sequence specificity. When used as rationally
      designed ZFR heterodimers, the reprogrammed enzyme variants site-specifically
      modified unnatural and asymmetric DNA sequences. Early studies on the directed
      evolution of serine recombinase DNA sequence specificity produced enzymes with
      relaxed substrate specificity as a result of randomly incorporated mutations. In
      the current study, we focused our mutagenesis exclusively on DNA determinants,
      leading to redesigned enzymes that remained highly specific and directed
      transgene integration into the human genome with > 80% accuracy. These results
      demonstrate that unique resolvase and invertase derivatives can be developed to
      site-specifically modify the human genome in the context of zinc-finger
      recombinase fusion proteins.

PMID- 21187419
TI  - Hexagonal assembly of a restricting TRIM5alpha protein.
AB  - TRIM5alpha proteins are restriction factors that protect mammalian cells from
      retroviral infections by binding incoming viral capsids, accelerating their
      dissociation, and preventing reverse transcription of the viral genome.
      Individual TRIM5 isoforms can often protect cells against a broad range of
      retroviruses, as exemplified by rhesus monkey TRIM5alpha and its variant, TRIM5
      21R, which recognize HIV-1 as well as several distantly related retroviruses.
      Although capsid recognition is not yet fully understood, previous work has shown
      that the C-terminal SPRY/B30.2 domain of dimeric TRIM5alpha binds directly to
      viral capsids, and that higher-order TRIM5alpha oligomerization appears to
      contribute to the efficiency of capsid recognition. Here, we report that
      recombinant TRIM5-21R spontaneously assembled into two-dimensional
      paracrystalline hexagonal lattices comprising open, six-sided rings. TRIM5-21R
      assembly did not require the C-terminal SPRY domain, but did require both protein
      dimerization and a B-box 2 residue (Arg121) previously implicated in TRIM5alpha
      restriction and higher-order assembly. Furthermore, TRIM5-21R assembly was
      promoted by binding to hexagonal arrays of the HIV-1 CA protein that mimic the
      surface of the viral capsid. We therefore propose that TRIM5alpha proteins have
      evolved to restrict a range of different retroviruses by assembling a deformable
      hexagonal scaffold that positions the capsid-binding domains to match the
      symmetry and spacing of the capsid surface lattice. Capsid recognition therefore
      involves a synergistic combination of direct binding interactions, avidity
      effects, templated assembly, and lattice complementarity.

PMID- 21187420
TI  - Cytoplasmic cAMP-sensing domain of hyperpolarization-activated cation (HCN)
      channels uses two structurally distinct mechanisms to regulate voltage gating.
AB  - Voltage gating of hyperpolarization-activated cation (HCN) channels is
      potentiated by direct binding of cAMP to a cytoplasmic cAMP-sensing domain (CSD).
      When unliganded, the CSD inhibits hyperpolarization-dependent opening of the HCN
      channel gate; cAMP binding relieves this autoinhibition so that opening becomes
      more favorable thermodynamically. This autoinhibition-relief mechanism is
      conserved with that of several other cyclic nucleotide receptors using the same
      ligand-binding fold. Besides its thermodynamic effect, cAMP also modulates the
      depolarization-dependent deactivation rate by kinetically trapping channels in an
      open state. Here we report studies of strong open-state trapping in an HCN
      channel showing that the well-established autoinhibition-relief model is
      insufficient. Whereas deletion of the CSD mimics the thermodynamic open-state
      stabilization usually associated with cAMP binding, CSD deletion removes rather
      than mimics the kinetic effect of strong open-state trapping. Substitution of
      different CSD sequences leads to variation of the degree of open-state trapping
      in the liganded channel but not in the unliganded channel. CSD-dependent open
      state trapping is observed during a voltage-dependent deactivation pathway,
      specific to the secondary open state that is formed by mode shift after prolonged
      hyperpolarization activation. This hysteretic activation-deactivation cycle is
      preserved by CSD substitution, but the change in deactivation kinetics of the
      liganded channel resulting from CSD substitution is not correlated with the
      change in autoinhibition properties. Thus the liganded and the unliganded forms
      of the CSD respectively provide the structural determinants for open-state
      trapping and autoinhibition, such that two distinct mechanisms for cAMP
      regulation can operate in one receptor.

PMID- 21187421
TI  - Tuning the ion selectivity of tetrameric cation channels by changing the number
      of ion binding sites.
AB  - Selective ion conduction across ion channel pores is central to cellular
      physiology. To understand the underlying principles of ion selectivity in
      tetrameric cation channels, we engineered a set of cation channel pores based on
      the nonselective NaK channel and determined their structures to high resolution.
      These structures showcase an ensemble of selectivity filters with a various
      number of contiguous ion binding sites ranging from 2 to 4, with each individual
      site maintaining a geometry and ligand environment virtually identical to that of
      equivalent sites in K(+) channel selectivity filters. Combined with single
      channel electrophysiology, we show that only the channel with four ion binding
      sites is K(+) selective, whereas those with two or three are nonselective and
      permeate Na(+) and K(+) equally well. These observations strongly suggest that
      the number of contiguous ion binding sites in a single file is the key
      determinant of the channel's selectivity properties and the presence of four
      sites in K(+) channels is essential for highly selective and efficient permeation
      of K(+) ions.

PMID- 21187422
TI  - Engineered Saccharomyces cerevisiae capable of simultaneous cellobiose and xylose
      fermentation.
AB  - The use of plant biomass for biofuel production will require efficient
      utilization of the sugars in lignocellulose, primarily glucose and xylose.
      However, strains of Saccharomyces cerevisiae presently used in bioethanol
      production ferment glucose but not xylose. Yeasts engineered to ferment xylose do
      so slowly, and cannot utilize xylose until glucose is completely consumed. To
      overcome these bottlenecks, we engineered yeasts to coferment mixtures of xylose
      and cellobiose. In these yeast strains, hydrolysis of cellobiose takes place
      inside yeast cells through the action of an intracellular beta-glucosidase
      following import by a high-affinity cellodextrin transporter. Intracellular
      hydrolysis of cellobiose minimizes glucose repression of xylose fermentation
      allowing coconsumption of cellobiose and xylose. The resulting yeast strains,
      cofermented cellobiose and xylose simultaneously and exhibited improved ethanol
      yield when compared to fermentation with either cellobiose or xylose as sole
      carbon sources. We also observed improved yields and productivities from
      cofermentation experiments performed with simulated cellulosic hydrolyzates,
      suggesting this is a promising cofermentation strategy for cellulosic biofuel
      production. The successful integration of cellobiose and xylose fermentation
      pathways in yeast is a critical step towards enabling economic biofuel
      production.

PMID- 21187423
TI  - Determination of second-order elliptic operators in two dimensions from partial
      Cauchy data.
AB  - We consider the inverse boundary value problem in two dimensions of determining
      the coefficients of a general second-order elliptic operator from the Cauchy data
      measured on a nonempty arbitrary relatively open subset of the boundary. We give
      a complete characterization of the set of coefficients yielding the same partial
      Cauchy data. As a corollary we prove several uniqueness results in determining
      coefficients from partial Cauchy data for the isotropic conductivity equation,
      the Schrodinger equation, the convection-diffusion equation, the anisotropic
      conductivity equation modulo a group of diffeomorphisms that are the identity at
      the boundary, and the magnetic Schrodinger equations modulo gauge
      transformations. The key step is the construction of novel complex geometrical
      optics solutions using Carleman estimates.

PMID- 21187424
TI  - Nonspecific binding limits the number of proteins in a cell and shapes their
      interaction networks.
AB  - Multicellular organisms, from Caenorhabditis elegans to humans, have roughly the
      same number of protein encoding genes. We show that the need to prevent disease
      causing nonspecific interactions between proteins provides a simple physical
      reason why organism complexity is not reflected in the number of distinct
      proteins. By collective evolution of the amino acid sequences of protein binding
      interfaces we estimate the degree of misbinding as a function of the number of
      distinct proteins. Protein interaction energies are calculated with an empirical,
      residue-specific energy function tuned for protein binding. We show that the
      achievable energy gap favoring specific over nonspecific binding decreases with
      protein number in a power-law fashion. From the fraction of proteins involved in
      nonspecific complexes as a function of increasing protein number and decreasing
      energy gap, we predict the limits these binding requirements place on the number
      of different proteins that can function effectively in a given cellular
      compartment. Remarkably, the optimization of binding interfaces favors networks
      in which a few proteins have many partners, and most proteins have few partners,
      consistent with a scale-free network topology. We conclude that nonspecific
      binding adds to the evolutionary pressure to develop scale-free protein-protein
      interaction networks.

PMID- 21187425
TI  - miR-29 and miR-30 regulate B-Myb expression during cellular senescence.
AB  - Cellular senescence is a form of irreversible growth arrest and a major tumor
      suppressor mechanism. We show here that the miR-29 and miR-30 microRNA families
      are up-regulated during induced and replicative senescence and that up-regulation
      requires activation of the Rb pathway. Expression of a reporter construct
      containing the 3'UTR of the B-Myb oncogene is repressed during senescence, and
      repression is blocked by mutations in conserved miR-29 and miR-30 binding sites
      in the B-Myb 3'UTR. In proliferating cells, transfection of miR-29 and miR-30
      represses a reporter construct containing the wild-type but not the mutant B-Myb
      3'UTR, and repression of the mutant 3'UTR is reinstituted by compensatory
      mutations in miR-29 and miR-30 that restore binding to the mutant sites. miR-29
      and miR-30 introduction also represses expression of endogenous B-Myb and
      inhibits cellular DNA synthesis. Finally, interference with miR-29 and miR-30
      expression inhibits senescence. These findings demonstrate that miR-29 and miR-30
      regulate B-Myb expression by binding to its 3'UTR and suggest that these
      microRNAs play an important role in Rb-driven cellular senescence.

PMID- 21187426
TI  - The Pim protein kinases regulate energy metabolism and cell growth.
AB  - The serine/threonine Pim kinases are overexpressed in solid cancers and
      hematologic malignancies and promote cell growth and survival. Here, we find that
      a novel Pim kinase inhibitor, SMI-4a, or Pim-1 siRNA blocked the rapamycin
      sensitive mammalian target of rapamycin (mTORC1) activity by stimulating the
      phosphorylation and thus activating the mTORC1 negative regulator AMP-dependent
      protein kinase (AMPK). Mouse embryonic fibroblasts (MEFs) deficient for all three
      Pim kinases [triple knockout (TKO) MEFs] demonstrated activated AMPK driven by
      elevated ratios of AMPATP relative to wild-type MEFs. Consistent with these
      findings, TKO MEFs were found to grow slowly in culture and have decreased rates
      of protein synthesis secondary to a diminished amount of 5'-cap-dependent
      translation. Pim-3 expression alone in TKO MEFs was sufficient to reverse AMPK
      activation, increase protein synthesis, and drive MEF growth similar to wild
      type. Pim-3 expression was found to markedly increase the protein levels of both
      c-Myc and the peroxisome proliferator-activated receptor gamma coactivator 1alpha
      (PGC-1alpha), enzymes capable of regulating glycolysis and mitochondrial
      biogenesis, which were diminished in TKO MEFs. Overexpression of PGC-1alpha in
      TKO MEFs elevated ATP levels and inhibited the activation of AMPK. These results
      demonstrate the Pim kinase-mediated control of energy metabolism and thus
      regulation of AMPK activity. We identify an important role for Pim-3 in
      modulating c-Myc and PGC-1alpha protein levels and cell growth.

PMID- 21187427
TI  - Folding of the Pit1 homeodomain near the speed limit.
AB  - Current questions in protein folding mechanisms include how fast can a protein
      fold and are there energy barriers for the folding and unfolding of ultrafast
      folding proteins? The small 3-helical engrailed homeodomain protein folds in 1.7
      MUs to form a well-characterized intermediate, which rearranges in 17 MUs to
      native structure. We found that the homologous pituitary-specific transcription
      factor homeodomain (Pit1) folded in a similar manner, but in two better separated
      kinetic phases of 2.3 and 46 MUs. The greater separation and better fluorescence
      changes facilitated a detailed kinetic analysis for the ultrafast phase for
      formation of the intermediate. Its folding rate constant changed little with
      denaturant concentration or mutation but unfolding was very sensitive to
      denaturant and energy changes on mutation. The folding rate constant of 3 * 10(5)
      s(-1) in water decreased with increasing viscosity, and was extrapolated to 4.4 *
      10(5) s(-1) at zero viscosity. Thus, the formation of the intermediate was partly
      rate limited by chain diffusion and partly by an energy barrier to give a very
      diffuse transition state, which was followed by the formation of structure.
      Conversely, the unfolding reaction required the near complete disruption of the
      tertiary structure of the intermediate in a highly cooperative manner, being
      exquisitely sensitive to individual mutations. The folding is approaching, but
      has not reached, the downhill-folding scenario of energy landscape theory. Under
      folding conditions, there is a small energy barrier between the denatured and
      transition states but a larger barrier between native and transition states.

PMID- 21187428
TI  - Methylation of histone H3 lysine 36 enhances DNA repair by nonhomologous end
      joining.
AB  - Given its significant role in the maintenance of genomic stability, histone
      methylation has been postulated to regulate DNA repair. Histone methylation
      mediates localization of 53BP1 to a DNA double-strand break (DSB) during
      homologous recombination repair, but a role in DSB repair by nonhomologous end
      joining (NHEJ) has not been defined. By screening for histone methylation after
      DSB induction by ionizing radiation we found that generation of dimethyl histone
      H3 lysine 36 (H3K36me2) was the major event. Using a novel human cell system that
      rapidly generates a single defined DSB in the vast majority of cells, we found
      that the DNA repair protein Metnase (also SETMAR), which has a SET histone
      methylase domain, localized to an induced DSB and directly mediated the formation
      of H3K36me2 near the induced DSB. This dimethylation of H3K36 improved the
      association of early DNA repair components, including NBS1 and Ku70, with the
      induced DSB, and enhanced DSB repair. In addition, expression of JHDM1a (an
      H3K36me2 demethylase) or histone H3 in which K36 was mutated to A36 or R36 to
      prevent H3K36me2 formation decreased the association of early NHEJ repair
      components with an induced DSB and decreased DSB repair. Thus, these experiments
      define a histone methylation event that enhances DNA DSB repair by NHEJ.

PMID- 21187429
TI  - Structural studies of ion permeation and Ca2+ blockage of a bacterial channel
      mimicking the cyclic nucleotide-gated channel pore.
AB  - Cyclic nucleotide-gated (CNG) channels play an essential role in the visual and
      olfactory sensory systems and are ubiquitous in eukaryotes. Details of their
      underlying ion selectivity properties are still not fully understood and are a
      matter of debate in the absence of high-resolution structures. To reveal the
      structural mechanism of ion selectivity in CNG channels, particularly their
      Ca(2+) blockage property, we engineered a set of mimics of CNG channel pores for
      both structural and functional analysis. The mimics faithfully represent the CNG
      channels they are modeled after, permeate Na(+) and K(+) equally well, and
      exhibit the same Ca(2+) blockage and permeation properties. Their high-resolution
      structures reveal a hitherto unseen selectivity filter architecture comprising
      three contiguous ion binding sites in which Na(+) and K(+) bind with different
      ion-ligand geometries. Our structural analysis reveals that the conserved acidic
      residue in the filter is essential for Ca(2+) binding but not through direct ion
      chelation as in the currently accepted view. Furthermore, structural insight from
      our CNG mimics allows us to pinpoint equivalent interactions in CNG channels
      through structure-based mutagenesis that have previously not been predicted using
      NaK or K(+) channel models.

PMID- 21187430
TI  - Formation of benzene in the interstellar medium.
AB  - Polycyclic aromatic hydrocarbons and related species have been suggested to play
      a key role in the astrochemical evolution of the interstellar medium, but the
      formation mechanism of even their simplest building block--the aromatic benzene
      molecule--has remained elusive for decades. Here we demonstrate in crossed
      molecular beam experiments combined with electronic structure and statistical
      calculations that benzene (C(6)H(6)) can be synthesized via the barrierless,
      exoergic reaction of the ethynyl radical and 1,3-butadiene, C(2)H +
      H(2)CCHCHCH(2) -> C(6)H(6) + H, under single collision conditions. This reaction
      portrays the simplest representative of a reaction class in which aromatic
      molecules with a benzene core can be formed from acyclic precursors via
      barrierless reactions of ethynyl radicals with substituted 1,3-butadiene
      molecules. Unique gas-grain astrochemical models imply that this low-temperature
      route controls the synthesis of the very first aromatic ring from acyclic
      precursors in cold molecular clouds, such as in the Taurus Molecular Cloud.
      Rapid, subsequent barrierless reactions of benzene with ethynyl radicals can lead
      to naphthalene-like structures thus effectively propagating the ethynyl-radical
      mediated formation of aromatic molecules in the interstellar medium.

PMID- 21187431
TI  - Reaction mechanism of Drosophila cryptochrome.
AB  - Cryptochrome (CRY) is a blue-light sensitive flavoprotein that functions as the
      primary circadian photoreceptor in Drosophila melanogaster. The mechanism by
      which it transmits the light signal to the core clock circuitry is not known. We
      conducted in vitro studies on the light-induced conformational change in CRY and
      its effect on protein-protein interaction and performed in vivo analysis of the
      lifetime of the signaling state of the protein to gain some insight into the
      mechanism of phototransduction. We find that exposure of CRY to blue light
      induces a conformation similar to that of the constitutively active CRY mutant
      with a C-terminal deletion (CRYDelta). This light-induced conformation has a half
      life of ~15 min in the dark at 25  degrees C and is characterized by increased
      affinity to Jetlag E3 ligase. In vivo analysis reveals that in the Drosophila S2
      cell line, the signaling state induced by a millisecond light exposure has a half
      life of 27 min in the dark at 0  degrees C during which period it is susceptible
      to degradation by the ubiquitin-proteasome system. These findings lead to a
      plausible model for circadian photoreception/phototransduction in Drosophila.

PMID- 21187432
TI  - Finding undetected protein associations in cell signaling by belief propagation.
AB  - External information propagates in the cell mainly through signaling cascades and
      transcriptional activation, allowing it to react to a wide spectrum of
      environmental changes. High-throughput experiments identify numerous molecular
      components of such cascades that may, however, interact through unknown partners.
      Some of them may be detected using data coming from the integration of a protein
      protein interaction network and mRNA expression profiles. This inference problem
      can be mapped onto the problem of finding appropriate optimal connected subgraphs
      of a network defined by these datasets. The optimization procedure turns out to
      be computationally intractable in general. Here we present a new distributed
      algorithm for this task, inspired from statistical physics, and apply this scheme
      to alpha factor and drug perturbations data in yeast. We identify the role of the
      COS8 protein, a member of a gene family of previously unknown function, and
      validate the results by genetic experiments. The algorithm we present is
      specially suited for very large datasets, can run in parallel, and can be adapted
      to other problems in systems biology. On renowned benchmarks it outperforms other
      algorithms in the field.

PMID- 21187433
TI  - Flotillins play an essential role in Niemann-Pick C1-like 1-mediated cholesterol
      uptake.
AB  - Dietary absorption is a major way for mammals to obtain cholesterol, which is
      mediated by Niemann-Pick C1-like 1 (NPC1L1) via vesicular endocytosis. One
      fundamental question in this process is how free cholesterol is efficiently taken
      up through the internalization of NPC1L1. Using exogenously expressed NPC1L1
      EGFP, we show that the lipid raft proteins flotillins associate with NPC1L1 and
      their localization is regulated by NPC1L1 during intracellular trafficking.
      Furthermore, flotillins are essential for NPC1L1-mediated cellular cholesterol
      uptake, biliary cholesterol reabsorption, and the regulation of lipid levels in
      mice. Together with NPC1L1, they form cholesterol-enriched membrane microdomains,
      which function as carriers for bulk of cholesterol. The hypocholesterolemic drug
      ezetimibe disrupts the association between NPC1L1 and flotillins, which blocks
      the formation of the cholesterol-enriched microdomains. Our findings reveal a
      functional role of flotillins in NPC1L1-mediated cholesterol uptake and elucidate
      the formation of NPC1L1-flotillins-postive cholesterol-enriched membrane
      microdomains as a mechanism for efficient cholesterol absorption.

PMID- 21187434
TI  - Coesite and stishovite in a shocked lunar meteorite, Asuka-881757, and impact
      events in lunar surface.
AB  - Microcrystals of coesite and stishovite were discovered as inclusions in
      amorphous silica grains in shocked melt pockets of a lunar meteorite Asuka-881757
      by micro-Raman spectrometry, scanning electron microscopy, electron back-scatter
      diffraction, and transmission electron microscopy. These high-pressure polymorphs
      of SiO(2) in amorphous silica indicate that the meteorite experienced an
      equilibrium shock-pressure of at least 8-30 GPa. Secondary quartz grains are also
      observed in separate amorphous silica grains in the meteorite. The estimated age
      reported by the (39)Ar/(40)Ar chronology indicates that the source basalt of this
      meteorite was impacted at 3,800 Ma ago, time of lunar cataclysm; i.e., the heavy
      bombardment in the lunar surface. Observation of coesite and stishovite formed in
      the lunar breccias suggests that high-pressure impact metamorphism and formation
      of high-pressure minerals are common phenomena in brecciated lunar surface
      altered by the heavy meteoritic bombardment.

PMID- 21187435
TI  - The noisy edge of traveling waves.
AB  - Traveling waves are ubiquitous in nature and control the speed of many important
      dynamical processes, including chemical reactions, epidemic outbreaks, and
      biological evolution. Despite their fundamental role in complex systems,
      traveling waves remain elusive because they are often dominated by rare
      fluctuations in the wave tip, which have defied any rigorous analysis so far.
      Here, we show that by adjusting nonlinear model details, noisy traveling waves
      can be solved exactly. The moment equations of these tuned models are closed and
      have a simple analytical structure resembling the deterministic approximation
      supplemented by a nonlocal cutoff term. The peculiar form of the cutoff shapes
      the noisy edge of traveling waves and is critical for the correct prediction of
      the wave speed and its fluctuations. Our approach is illustrated and benchmarked
      using the example of fitness waves arising in simple models of microbial
      evolution, which are highly sensitive to number fluctuations. We demonstrate
      explicitly how these models can be tuned to account for finite population sizes
      and determine how quickly populations adapt as a function of population size and
      mutation rates. More generally, our method is shown to apply to a broad class of
      models, in which number fluctuations are generated by branching processes.
      Because of this versatility, the method of model tuning may serve as a promising
      route toward unraveling universal properties of complex discrete particle
      systems.

PMID- 21187436
TI  - Gene expression patterns of Th2 inflammation and intercellular communication in
      asthmatic airways.
AB  - Asthma is canonically thought of as a disorder of excessive Th2-driven
      inflammation in the airway, although recent studies have described heterogeneity
      with respect to asthma pathophysiology. We have previously described distinct
      phenotypes of asthma based on the presence or absence of a three-gene "Th2
      signature" in bronchial epithelium, which differ in terms of eosinophilic
      inflammation, mucin composition, subepithelial fibrosis, and corticosteroid
      responsiveness. In the present analysis, we sought to describe Th2 inflammation
      in human asthmatic airways quantitatively with respect to known mediators of
      inflammation and intercellular communication. Using whole-genome microarray and
      quantitative real-time PCR analysis of endobronchial biopsies from 27 mild-to
      moderate asthmatics and 13 healthy controls with associated clinical and
      demographic data, we found that asthmatic Th2 inflammation is expressed over a
      variable continuum, correlating significantly with local and systemic measures of
      allergy and eosinophilia. We evaluated a composite metric describing 79
      coexpressed genes associated with Th2 inflammation against the biological space
      comprising cytokines, chemokines, and growth factors, identifying distinctive
      patterns of inflammatory mediators as well as Wnt, TGF-beta, and platelet-derived
      growth factor family members. This integrated description of the factors
      regulating inflammation, cell migration, and tissue remodeling in asthmatic
      airways has important consequences for the pathophysiological and clinical
      impacts of emerging asthma therapeutics targeting Th2 inflammation.

PMID- 21187437
TI  - Pyk2 is required for neutrophil degranulation and host defense responses to
      bacterial infection.
AB  - The appropriate regulation of neutrophil activation is critical for maintaining
      host defense and limiting inflammation. Polymorphonuclear neutrophils (PMNs)
      express a number of cytoplasmic tyrosine kinases that regulate signaling pathways
      leading to activation. One of the most highly expressed, but least studied,
      kinases in PMNs is proline rich kinase 2 (Pyk2). By analogy to the related focal
      adhesion kinase, Pyk2 has been implicated in regulating PMN adhesion and
      migration; however, its physiologic function has yet to be described. Using pyk2(
      /-) mice, we found that this kinase was required for integrin-mediated
      degranulation responses, but was not involved in adhesion-induced cell spreading
      or activation of superoxide production. Pyk2-deficient PMNs also manifested
      reduced migration on fibrinogen-coated surfaces. The absence of Pyk2 resulted in
      a severe reduction in paxillin and Vav phosphorylation following integrin
      ligation, which likely accounts for the poor degranulation and cell migration.
      Pyk2(-/-) mice were unable to efficiently clear infection with Staphylococcus
      aureus in a skin abscess model, owing in part to the poor release of granule
      contents at the site of infection. However, Pyk2-deficient PMNs responded
      normally to soluble agonists, demonstrating that this kinase functions mainly in
      the integrin pathway. These data demonstrate the unrealized physiologic role of
      this kinase in regulating the adhesion-mediated release of PMN granule contents.

PMID- 21187438
TI  - RIG-I/MDA5/MAVS are required to signal a protective IFN response in rotavirus
      infected intestinal epithelium.
AB  - Rotavirus is a dsRNA virus that infects epithelial cells that line the surface of
      the small intestine. It causes severe diarrheal illness in children and ~500,000
      deaths per year worldwide. We studied the mechanisms by which intestinal
      epithelial cells (IECs) sense rotavirus infection and signal IFN-beta production,
      and investigated the importance of IFN-beta production by IECs for controlling
      rotavirus production by intestinal epithelium and virus excretion in the feces.
      In contrast with most RNA viruses, which interact with either retinoic acid
      inducible gene I (RIG-I) or melanoma differentiation-associated gene 5 (MDA5)
      inside cells, rotavirus was sensed by both RIG-I and MDA5, alone and in
      combination. Rotavirus did not signal IFN-beta through either of the dsRNA
      sensors TLR3 or dsRNA-activated protein kinase (PKR). Silencing RIG-I or MDA5, or
      their common adaptor protein mitochondrial antiviral signaling protein (MAVS),
      significantly decreased IFN-beta production and increased rotavirus titers in
      infected IECs. Overexpression of laboratory of genetics and physiology 2, a RIG-I
      like receptor that interacts with viral RNA but lacks the caspase activation and
      recruitment domains required for signaling through MAVS, significantly decreased
      IFN-beta production and increased rotavirus titers in infected IECs. Rotavirus
      infected mice lacking MAVS, but not those lacking TLR3, TRIF, or PKR, produced
      significantly less IFN-beta and increased amounts of virus in the intestinal
      epithelium, and shed increased quantities of virus in the feces. We conclude that
      RIG-I or MDA5 signaling through MAVS is required for the activation of IFN-beta
      production by rotavirus-infected IECs and has a functionally important role in
      determining the magnitude of rotavirus replication in the intestinal epithelium.

PMID- 21187440
TI  - Functional consequences of natural sequence variation of murine cytomegalovirus
      m157 for Ly49 receptor specificity and NK cell activation.
AB  - The Ly49H activating receptor on C57BL/6 (B6) NK cells plays a key role in early
      resistance to murine cytomegalovirus (MCMV) infection through specific
      recognition of the MCMV-encoded MHC class I-like molecule m157 expressed on
      infected cells. The m157 molecule is also recognized by the Ly49I inhibitory
      receptor from the 129/J mouse strain. The m157 gene is highly sequence variable
      among MCMV isolates, with many m157 variants unable to bind Ly49H(B6). In this
      study, we have sought to define if m157 variability leads to a wider spectrum of
      interactions with other Ly49 molecules and if this modifies host susceptibility
      to MCMV. We have identified novel m157-Ly49 receptor interactions, involving
      Ly49C inhibitory receptors from B6, BALB/c, and NZB mice, as well as the
      Ly49H(NZB) activation receptor. Using an MCMV recombinant virus in which
      m157(K181) was replaced with m157(G1F), which interacts with both Ly49H(B6) and
      Ly49C(B6), we show that the m157(G1F)-Ly49C interactions cause no apparent
      attenuating effect on viral clearance in B6 mice. Hence, when m157 can bind both
      inhibitory and activation NK cell receptors, the outcome is still activation.
      Thus, these data indicate that whereas m157 variants predominately interact with
      inhibitory Ly49 receptors, these interactions do not profoundly interfere with
      early NK cell responses.

PMID- 21187439
TI  - In situ B cell-mediated immune responses and tubulointerstitial inflammation in
      human lupus nephritis.
AB  - The most prevalent severe manifestation of systemic lupus erythematosus is
      nephritis, which is characterized by immune complex deposition, inflammation, and
      scarring in glomeruli and the tubulointerstitium. Numerous studies indicated that
      glomerulonephritis results from a systemic break in B cell tolerance, resulting
      in the local deposition of immune complexes containing Abs reactive with
      ubiquitous self-Ags. However, the pathogenesis of systemic lupus erythematosus
      tubulointerstitial disease is not known. In this article, we demonstrate that in
      more than half of a cohort of 68 lupus nephritis biopsies, the tubulointerstitial
      infiltrate was organized into well-circumscribed T:B cell aggregates or germinal
      centers (GCs) containing follicular dendritic cells. Sampling of the in situ
      expressed Ig repertoire revealed that both histological patterns were associated
      with intrarenal B cell clonal expansion and ongoing somatic hypermutation.
      However, in the GC histology, the proliferating cells were CD138(-)CD20(+)
      centroblasts, whereas they were CD138(+)CD20(low/-) plasmablasts in T:B
      aggregates. The presence of GCs or T:B aggregates was strongly associated with
      tubular basement membrane immune complexes. These data implicate tertiary
      lymphoid neogenesis in the pathogenesis of lupus tubulointerstitial inflammation.

PMID- 21187441
TI  - Provision of continuous maturation signaling to dendritic cells by RIG-I
      stimulating cytosolic RNA synthesis of Sendai virus.
AB  - Dendritic cell (DC)-based immunotherapy has potential for treating infections and
      malignant tumors, but the functional capacity of DC must be assessed in detail,
      especially maturation and Ag-specific CTL priming. Recent reports suggest that DC
      that are provided with continuous maturation signals in vivo after transfer into
      patients are required to elicit the full DC functions. We demonstrate in this
      study that the rSendai virus vector (SeV) is a novel and ideal stimulant,
      providing DC with a continuous maturation signal via viral RNA synthesis in the
      cytosol, resulting in full maturation of monocyte-derived DC(s). Both RIG-I
      dependent cytokine production and CD4 T cell responses to SeV-derived helper Ags
      are indispensable for overcoming regulatory T cell suppression to prime melanoma
      Ag recognized by T cell-1-specific CTL in the regulatory T cell abundant setting.
      DC stimulated via cytokine receptors, or TLRs, do not show these functional
      features. Therefore, SeV-infected DC have the potential for DC-directed
      immunotherapy.

PMID- 21187442
TI  - Postselection thymocyte maturation and emigration are independent of IL-7 and
      ERK5.
AB  - The transcription factor Kruppel-like factor 2 (KLF2) controls the emigration of
      conventional T cells from the thymus through its regulation of the cell surface
      receptor S1P1. Prior to KLF2 expression, developing T cells require a positive
      selection signal through the TCR. However, following positive selection there are
      time, spatial, and maturational events that occur before KLF2 is finally
      upregulated and emigration occurs. We are interested in determining the signals
      that upregulate KLF2 and allow thymocytes to emigrate into circulation and
      whether they are linked to functional maturation. In endothelial cells KLF2
      expression has been shown to be dependent on the mitogen-activated protein kinase
      ERK5. Furthermore, it has been reported that IL-7 signaling leads to the
      phosphorylation of ERK5. Thus, we hypothesized that IL-7R signaling through ERK5
      could drive the expression of KLF2. In this study, we provide evidence that this
      hypothesis is incorrect. We also found that CD8 lineage specification occurred
      normally in the absence of IL-7R signaling, in contrast to a recently proposed
      model. We showed that both CD4 and CD8 T cells complete maturation and express
      KLF2 independently of ERK5 and IL-7.

PMID- 21187443
TI  - Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing
      of multiple myeloma and other hematological tumors.
AB  - CD38, a type II transmembrane glycoprotein highly expressed in hematological
      malignancies including multiple myeloma (MM), represents a promising target for
      mAb-based immunotherapy. In this study, we describe the cytotoxic mechanisms of
      action of daratumumab, a novel, high-affinity, therapeutic human mAb against a
      unique CD38 epitope. Daratumumab induced potent Ab-dependent cellular
      cytotoxicity in CD38-expressing lymphoma- and MM-derived cell lines as well as in
      patient MM cells, both with autologous and allogeneic effector cells. Daratumumab
      stood out from other CD38 mAbs in its strong ability to induce complement
      dependent cytotoxicity in patient MM cells. Importantly, daratumumab-induced Ab
      dependent cellular cytotoxicity and complement-dependent cytotoxicity were not
      affected by the presence of bone marrow stromal cells, indicating that
      daratumumab can effectively kill MM tumor cells in a tumor-preserving bone marrow
      microenvironment. In vivo, daratumumab was highly active and interrupted
      xenograft tumor growth at low dosing. Collectively, our results show the
      versatility of daratumumab to effectively kill CD38-expressing tumor cells,
      including patient MM cells, via diverse cytotoxic mechanisms. These findings
      support clinical development of daratumumab for the treatment of CD38-positive MM
      tumors.

PMID- 21187445
TI  - Spontaneous pregnancy loss mediated by abnormal maternal inflammation in rats is
      linked to deficient uteroplacental perfusion.
AB  - Abnormal maternal inflammation during pregnancy is associated with spontaneous
      pregnancy loss and intrauterine fetal growth restriction. However, the mechanisms
      responsible for these pregnancy outcomes are not well understood. In this study,
      we used a rat model to demonstrate that pregnancy loss resulting from aberrant
      maternal inflammation is closely linked to deficient placental perfusion.
      Administration of LPS to pregnant Wistar rats on gestational day 14.5, to induce
      maternal inflammation, caused fetal loss in a dose-dependent manner 3-4 h later,
      and surviving fetuses were significantly growth restricted. Pregnancy loss was
      associated with coagulopathy, structural abnormalities in the uteroplacental
      vasculature, decreased placental blood flow, and placental and fetal hypoxia
      within 3 h of LPS administration. This impairment in uteroplacental hemodynamics
      in LPS-treated rats was linked to increased uterine artery resistance and reduced
      spiral arteriole flow velocity. Pregnancy loss induced by LPS was prevented by
      maternal administration of the immunoregulatory cytokine IL-10 or by blocking TNF
      alpha activity after treatment with etanercept (Enbrel). These results indicate
      that alterations in placental perfusion are responsible for fetal morbidities
      associated with aberrant maternal inflammation and support a rationale for
      investigating a potential use of immunomodulatory agents in the prevention of
      spontaneous pregnancy loss.

PMID- 21187444
TI  - Langerin+ dermal dendritic cells are critical for CD8+ T cell activation and IgH
      gamma-1 class switching in response to gene gun vaccines.
AB  - The C-type lectin langerin/CD207 was originally discovered as a specific marker
      for epidermal Langerhans cells (LC). Recently, additional and distinct subsets of
      langerin(+) dendritic cells (DC) have been identified in lymph nodes and
      peripheral tissues of mice. Although the role of LC for immune activation or
      modulation is now being discussed controversially, other langerin(+) DC appear
      crucial for protective immunity in a growing set of infection and vaccination
      models. In knock-in mice that express the human diphtheria toxin receptor under
      control of the langerin promoter, injection of diphtheria toxin ablates LC for
      several weeks whereas other langerin(+) DC subsets are replenished within just a
      few days. Thus, by careful timing of diphtheria toxin injections selective states
      of deficiency in either LC only or all langerin(+) cells can be established.
      Taking advantage of this system, we found that, unlike selective LC deficiency,
      ablation of all langerin(+) DC abrogated the activation of IFN-gamma-producing
      and cytolytic CD8(+) T cells after gene gun vaccination. Moreover, we identified
      migratory langerin(+) dermal DC as the subset that directly activated CD8(+) T
      cells in lymph nodes. Langerin(+) DC were also critical for IgG1 but not IgG2a Ab
      induction, suggesting differential polarization of CD4(+) T helper cells by
      langerin(+) or langerin-negative DC, respectively. In contrast, protein vaccines
      administered with various adjuvants induced IgG1 independently of langerin(+) DC.
      Taken together, these findings reflect a highly specialized division of labor
      between different DC subsets both with respect to Ag encounter as well as
      downstream processes of immune activation.

PMID- 21187446
TI  - TNF receptor-1 is required for the formation of splenic compartments during
      adult, but not embryonic life.
AB  - Lymphotoxin beta-receptor (LTbetaR) and TNF receptor-1 (TNFR1) are important for
      the development of secondary lymphoid organs during embryonic life. The
      significance of LTbetaR and TNFR1 for the formation of lymphoid tissue during
      adult life is not well understood. Immunohistochemistry, morphometry, flow
      cytometry, and laser microdissection were used to compare wild-type, LTbetaR(-/
      ), TNFR1(-/-) spleens with splenic tissue that has been newly formed 8 wk after
      avascular implantation into adult mice. During ontogeny, LTbetaR is sufficient to
      induce formation of the marginal zone, similar-sized T and B cell zones, and a
      mixed T/B cell zone that completely surrounded the T cell zone. Strikingly, in
      adult mice, the formation of splenic compartments required both LTbetaR and TNFR1
      expression, demonstrating that the molecular requirements for lymphoid tissue
      formation are different during embryonic and adult life. Thus, interfering with
      the TNFR1 pathway offers the possibility to selectively block the formation of
      ectopic lymphoid tissue and at the same time to spare secondary lymphoid organs
      such as spleen and lymph nodes. This opens a new perspective for the treatment of
      autoimmune and inflammatory diseases.

PMID- 21187447
TI  - CR2+ marginal zone B cell production of pathogenic natural antibodies is C3
      independent.
AB  - Intestinal ischemia-reperfusion (IR)-induced damage requires complement receptor
      2 (CR2) for generation of the appropriate natural Ab repertoire. Pathogenic Abs
      recognize neoantigens on the ischemic tissue, activate complement, and induce
      intestinal damage. Because C3 cleavage products act as ligands for CR2, we
      hypothesized that CR2(hi) marginal zone B cells (MZBs) require C3 for generation
      of the pathogenic Abs. To explore the ability of splenic CR2(+) B cells to
      generate the damaging Ab repertoire, we adoptively transferred either MZBs or
      follicular B cells (FOBs) from C57BL/6 or Cr2(-/-) mice into Rag-1(-/-) mice.
      Adoptive transfer of wild type CR2(hi) MZBs but not CR2(lo) FOBs induced
      significant damage, C3 deposition, and inflammation in response to IR. In
      contrast, similarly treated Rag-1(-/-) mice reconstituted with either Cr2(-/-)
      MZB/B1 B cells (B1Bs) or FOBs lacked significant intestinal damage and displayed
      limited complement activation. To determine whether C3 cleavage products are
      critical in CR2-dependent Ab production, we evaluated the ability of the natural
      Ab repertoire of C3(-/-) mice to induce damage in response to IR. Infusion of C3(
      /-) serum into Cr2(-/-) mice restored IR-induced tissue damage. Furthermore, Rag
      1(-/-) mice sustained significant damage after infusion of Abs from C3(-/-) but
      not Cr2(-/-) mice. Finally, adoptive transfer of MZBs from C3(-/-) mice into Rag
      1(-/-) mice resulted in significant tissue damage and inflammation. These data
      indicate that CR2 expression on MZBs is sufficient to induce the appropriate Abs
      required for IR-induced tissue damage and that C3 is not critical for generation
      of the pathogenic Abs.

PMID- 21187448
TI  - Controlling herpes simplex virus-induced ocular inflammatory lesions with the
      lipid-derived mediator resolvin E1.
AB  - Stromal keratitis (SK) is a chronic immunopathological lesion of the eye caused
      by HSV-1 infection and a common cause of blindness in humans. The inflammatory
      lesions are primarily perpetuated by neutrophils with the active participation of
      CD4(+) T cells. Therefore, targeting these immune cell types represents a
      potentially valuable form of therapy to reduce the severity of disease. Resolvin
      E1 (RvE1), an endogenous lipid mediator, was shown to promote resolution in
      several inflammatory disease models. In the current report, we determined whether
      RvE1 administration begun at different times after ocular infection of mice with
      HSV could influence the severity of SK lesions. Treatment with RvE1 significantly
      reduced the extent of angiogenesis and SK lesions that occurred. RvE1-treated
      mice had fewer numbers of inflammatory cells that included Th1 and Th17 cells as
      well as neutrophils in the cornea. The mechanisms by which RvE1 acts appear to be
      multiple. These included reducing the influx of neutrophils and pathogenic CD4(+)
      T cells, increasing production of the anti-inflammatory cytokine IL-10, and
      inhibitory effects on the production of proinflammatory mediators and molecules,
      such as IL-6, IFN-gamma, IL-17, KC, VEGF-A, MMP-2, and MMP-9, that are involved
      in corneal neovascularization and SK pathogenesis. These findings are, to our
      knowledge, the first to show that RvE1 treatment could represent a novel approach
      to control lesion severity in a virally induced immunopathological disease.

PMID- 21187449
TI  - CpG promotes cross-presentation of dead cell-associated antigens by pre-CD8alpha+
      dendritic cells [corrected].
AB  - Cross-presentation of cell-associated Ags by dendritic cells (DC) plays an
      important role in immunity. DC in lymphoid tissues are short lived, being
      continuously replaced by precursors that proliferate and differentiate locally.
      Paradoxically, although TLR ligands promote immune responses and stimulate DC
      replenishment, they impair the cross-priming capacity of terminally
      differentiated splenic CD8alpha(+) DC, the major subset involved in cross
      priming. In this study, we have investigated the cross-presentation capacity of
      newly generated murine DC and especially immediate precursors of CD8alpha(+) DC.
      We show that these DC do not cross-present Ag from dead cells unless stimulated
      by TLR ligands before Ag capture. TLR ligand CpG induced the expression of
      costimulatory molecules required for CD8 T cell activation but also regulated the
      intracellular mechanisms of cross-presentation such as Ag degradation rates
      without regulating Ag uptake. GM-CSF, an inflammatory cytokine associated with
      infections, also promoted cross-presentation acquisition by pre-CD8alpha(+) DC
      and synergized with TLR9 ligand. The concept that TLR ligands as well as
      inflammatory cytokines promote the acquisition of cross-presenting properties by
      pre-CD8alpha(+) DC has important implications during immune responses and when
      considering the use of these cells for vaccination.

PMID- 21187450
TI  - Dragon (repulsive guidance molecule b) inhibits IL-6 expression in macrophages.
AB  - Repulsive guidance molecule (RGM) family members RGMa, RGMb/Dragon, and
      RGMc/hemojuvelin were found recently to act as bone morphogenetic protein (BMP)
      coreceptors that enhance BMP signaling activity. Although our previous studies
      have shown that hemojuvelin regulates hepcidin expression and iron metabolism
      through the BMP pathway, the role of the BMP signaling mediated by Dragon remains
      largely unknown. We have shown previously that Dragon is expressed in neural
      cells, germ cells, and renal epithelial cells. In this study, we demonstrate that
      Dragon is highly expressed in macrophages. Studies with RAW264.7 and J774
      macrophage cell lines reveal that Dragon negatively regulates IL-6 expression in
      a BMP ligand-dependent manner via the p38 MAPK and Erk1/2 pathways but not the
      Smad1/5/8 pathway. We also generated Dragon knockout mice and found that IL-6 is
      upregulated in macrophages and dendritic cells derived from whole lung tissue of
      these mice compared with that in respective cells derived from wild-type
      littermates. These results indicate that Dragon is an important negative
      regulator of IL-6 expression in immune cells and that Dragon-deficient mice may
      be a useful model for studying immune and inflammatory disorders.

PMID- 21187451
TI  - Improving marginal likelihood estimation for Bayesian phylogenetic model
      selection.
AB  - The marginal likelihood is commonly used for comparing different evolutionary
      models in Bayesian phylogenetics and is the central quantity used in computing
      Bayes Factors for comparing model fit. A popular method for estimating marginal
      likelihoods, the harmonic mean (HM) method, can be easily computed from the
      output of a Markov chain Monte Carlo analysis but often greatly overestimates the
      marginal likelihood. The thermodynamic integration (TI) method is much more
      accurate than the HM method but requires more computation. In this paper, we
      introduce a new method, steppingstone sampling (SS), which uses importance
      sampling to estimate each ratio in a series (the "stepping stones") bridging the
      posterior and prior distributions. We compare the performance of the SS approach
      to the TI and HM methods in simulation and using real data. We conclude that the
      greatly increased accuracy of the SS and TI methods argues for their use instead
      of the HM method, despite the extra computation needed.

PMID- 21187453
TI  - Constitutive activation of LXR in macrophages regulates metabolic and
      inflammatory gene expression: identification of ARL7 as a direct target.
AB  - Ligand activation of liver X receptors (LXRs) has been shown to impact both lipid
      metabolism and inflammation. One complicating factor in studies utilizing
      synthetic LXR agonists is the potential for pharmacologic and receptor
      independent effects. Here, we describe an LXR gain-of-function system that does
      not depend on the addition of exogenous ligand. We generated transgenic mice
      expressing a constitutively active VP16-LXRalpha protein from the aP2 promoter.
      These mice exhibit increased LXR signaling selectively in adipose and
      macrophages. Analysis of gene expression in primary macrophages derived from two
      independent VP16-LXRalpha transgenic lines confirmed the ability of LXR to drive
      expression of genes involved in cholesterol efflux and fatty acid synthesis.
      Moreover, VP16-LXRalpha expression also suppressed the induction of inflammatory
      genes by lipopolysaccharide to a comparable degree as synthetic agonist. We
      further utilized VP16-LXRalpha-expressing macrophages to identify and validate
      new targets for LXRs, including the gene encoding ADP-ribosylation factor-like 7
      (ARL7). ARL7 has previously been shown to transport cholesterol to the membrane
      for ABCA1-associated removal and thus may be integral to the LXR-dependent efflux
      pathway. We show that the ARL7 promoter contains a functional LXRE and can be
      transactivated by LXRs in a sequence-specific manner, indicating that ARL7 is a
      direct target of LXR. These findings provide further support for an important
      role of LXRs in the coordinated regulation of lipid metabolic and inflammatory
      gene programs in macrophages.

PMID- 21187454
TI  - CCL2 expression in primary ovarian carcinoma is correlated with chemotherapy
      response and survival outcomes.
AB  - CCL2, a chemokine, is expressed in normal human ovarian epithelium but down
      regulated in ovarian adenocarcinomas. The association of CCL2 expression with
      chemotherapy response, invasion and survival outcomes was studied in patients
      with primary ovarian cancer (OC) and in ovarian cancer cell lines (OCCLs). Tumor
      specimens (>80% tumor) from patients with primary, advanced serous OC obtained at
      the time of cytoreductive surgery was used to isolate total RNA. The CCL2 gene
      expression evaluated by RT-PCR was investigated in relation to chemo
      response/clinical outcomes in the OC patients and to sensitivity to
      cisplatin/paclitaxel in the OCCLs. In vitro invasion was measured by matrigel
      invasion and matrixmetallo-proteinase-9 (MMP-9) zymogram assays. Thirty-seven
      patients were included. In multivariable analyses that adjusted for the impact of
      debulking status, the CCL2 mRNA expression was correlated with objective complete
      response (p = 0.01), chemosensitivity (p = 0.04), and progression-free survival
      (PFS; p = 0.006). These findings were corroborated in vitro in the OCCLs. The
      cells expressing higher levels of CCL2 were more sensitive to paclitaxel and
      cisplatin as compared to those lines expressing lower levels of this chemokine.
      Up-regulation of CCL2 in the PAT-7 cell line further enhanced the response of
      these cells to paclitaxel (p = 0.0001) and led to decreased invasion (p =
      0.0009). Increased ovarian tumoral expression of CCL2 is associated with improved
      chemoresponse and survival outcomes, and higher levels of CCL2 in ovarian cancer
      cell lines are associated with increased chemosensitivity and decreased invasion
      in vitro.

PMID- 21187455
TI  - A clinically relevant, syngeneic model of spontaneous, highly metastatic B16
      mouse melanoma.
AB  - We report a syngeneic model of spontaneous metastatic B16-F10 mouse melanoma in
      C57/BL6 mice with a very high metastatic frequency that mimics clinical
      metastatic melanoma. The B16 melanoma cells were injected between the skin and
      cartilage on the dorsal side of the ear. The model generated lymphatic and
      visceral metastases in all of the tested animals. In mice with large primary
      tumors, tumor weight correlated with the tumor growth time and also with the
      number of metastases in lymph nodes and organs. The dorsal ear space between the
      skin and cartilage enables both lymphatic and hematogenous metastatic spread. The
      model should be useful to study the mechanism of melanoma metastasis and to
      develop therapy for this currently untreatable disease.

PMID- 21187456
TI  - Expression of anti-apoptosis genes determines the response of adrenal cancer to
      apoptosis-inducing chemotherapy.
AB  - BACKGROUND: This study tested the hypothesis that response of adrenal cortical
      carcinoma (ACC) to pro-apoptosis drugs depends on expression of anti-apoptosis
      genes. MATERIALS AND METHODS: Expression of Bcl-2 and Bcl-XL proteins was
      determined in two human adrenal cancer cell lines, NCI-H-295 and RL-251. Two pro
      apoptosis drugs, gossypol (G) and docetaxel (D) were tested in vitro and in vivo
      in a human ACC/SCID mouse chimera. RESULTS: Bcl-XL was strongly expressed in RL
      251 but not in H-295 and neither expressed the Bcl-2 protein. G and D induced
      greater dose-dependent inhibition of cell proliferation in RL-251 than in H-295
      cells and completely suppressed growth of tumors with high expression of Bcl-XL
      (p<0.05) while there was no growth suppression in tumors without Bcl-XL
      expression. CONCLUSION: This study provided proof of concept that expression of
      Bcl-XL determines response to pro-apoptosis drugs. Profiling adrenal tumors for
      expression of anti-apoptosis genes may provide clues to their potential response
      to drugs that induce apoptosis.

PMID- 21187457
TI  - Aberrant methylation of heparan sulfate glucosamine 3-O-sulfotransferase 2 genes
      as a biomarker in colorectal cancer.
AB  - AIM: The first aim was to determine whether hypermethylation of certain tumor
      related genes, including 3OST2, CHFR, RUNX3, and p16, could be detected in
      Japanese colorectal cancer (CRC) patients. The second was to utilize the most
      frequently hypermethylated genes as biomarkers for early detection of CRC.
      MATERIALS AND METHODS: We investigated the aberrant promoter methylation profile
      of 4 genes in 129 colorectal tumors and corresponding normal mucosa. For the
      second step, bowel lavage and blood of the main tumor drainage vein from 21 CRC
      patients were analyzed. RESULTS: The 3OST2 gene was the most frequently
      methylated (57%) and was methylated frequently (9/21, 43%) in bowel lavage but
      rarely (1/21; 4.7%) in the venous drainage. The concordance between 3OST2
      methylation in bowel lavage and corresponding tumor samples was 71.4%.
      CONCLUSION: These results may show the possibility of early detection for CRC by
      examining 3OST2 gene methylation status in DNA extracted from stool.

PMID- 21187458
TI  - Inhibition of L-type amino acid transporter 1 has antitumor activity in non-small
      cell lung cancer.
AB  - BACKGROUND: L-type amino acid transporter 1 (LAT1) is highly expressed in various
      human neoplasms. Antitumor activity of inhibiting LAT1 was analyzed in non-small
      cell lung cancer (NSCLC). MATERIALS AND METHODS: Expression of LAT1 mRNA in 54
      lung cancer cell lines was examined by RT-PCR. An inhibitor of LAT1, 2
      aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), was administered to H1395
      cell. LAT1 expression was examined in correlation with clinical features and
      outcome in 51 NSCLC patients. RESULTS: Inhibition of LAT1 by BCH reduced cell
      viability in H1395 cells. Furthermore, co-administration of gefitinib with BCH
      reduced the viability of the cells more than either agent alone. Inhibition of
      LAT1 reduced the level of phosphorylation of mTOR, p70S6K and 4EBP1. LAT1 protein
      expression was closely associated with wild type EGFR, and was an independent
      significant factor to predict a poor prognosis. CONCLUSION: Inhibition of LAT1
      may be a new rationale to the effective therapy of NSCLC without EGFR mutation.

PMID- 21187459
TI  - Differential stimulation of VEGF-C production by adhesion/growth-regulatory
      galectins and plant lectins in human breast cancer cells.
AB  - The present study tested the hypothesis that the production of vascular
      endothelial growth factor C (VEGF-C), a key lymphangiogenic factor, by human
      breast cancer cells can be stimulated by human lectins, using plant lectins as
      controls. MATERIALS AND METHODS: The effects of human galectins and five plant
      lectins reacting with distinct determinants of N- and O-glycans on the
      accumulation of VEGF-C in serum-free cell culture media of human breast cancer
      cells endowed with high (MDA-MB-231) and low (MCF7, T-47D, and SK-BR-3) VEGF-C
      producing abilities were examined. RESULTS: All tested lectins stimulated VEGF-C
      production by MDA-MB-231 cells, albeit with different potency. Concanavalin A,
      but not galectins, was also able to stimulate VEGF-C production by low VEGF-C
      producing cell lines MCF7 and T-47D. Both VEGF-C mRNA and protein were strongly
      up-regulated in SK-BR-3 cells by concanavalin A and wheat germ agglutinin, but
      not jacalin. CONCLUSION: The differential response of breast cancer cell lines
      separated by the endogenous level of VEGF-C production suggests that galectins
      may contribute to tumor-associated lymphangiogenesis in a cell-specific manner.

PMID- 21187460
TI  - MCF-7 cell apoptosis and cell cycle arrest: non-genomic effects of progesterone
      and mifepristone (RU-486).
AB  - The pharmacology of progestins includes actions initiated by various cellular
      targets, including classic receptors characterized as nuclear transcription
      factors (nPR), G-protein-coupled membrane receptors (mPR), enzymes, membrane
      channels and transporters. The effects initiated by targets other than nPR are
      termed non-genomic and there is an increasing recognition that these effects also
      play an important role in the regulation of cell growth. MATERIALS AND METHODS:
      The nPR-positive breast cancer (MCF-7) and the nPR-negative uterine cervix cancer
      (C4-I) cell lines were exposed to progesterone (PG) and mifepristone (MF) during
      a culture period of 96 h. Daily cell count, cell cycle analysis and apoptosis
      assay were performed. RESULTS: It was possible to separate the nPR initiated
      effects (growth stimulation) from the non-genomic effects (growth inhibition) in
      the MCF-7 cells. Below 1 MUM PG treatment gave a small, but distinct increase in
      cell density which was effectively blocked by MF. Such an effect was absent from
      the nPR-negative C4-I cells. For a range of concentrations between 1 MUM and 100
      MUM, the effect of both PG and MF developed over time and showed concentration
      dependency. The PG concentrations needed to reduce cell density by 50% (IC(50))
      were 12.8 +/- 1.1 MUM and 6.5 +/- 0.2 MUM for the MCF-7 and C4-I cells,
      respectively. MF appeared to be equally or slightly more potent, with respective
      IC(50) values of 6.9 +/- 0.5 MUM and 5.3 +/- 0.3 MUM. The cell density reduction
      was both a result of cell cycle arrest and apoptosis. The combination of PG and
      MF had a potentiated effect on cell density reduction, cell cycle arrest and
      apoptosis. CONCLUSION: The antiproliferative/cytotoxic effect of PG and MF in
      concentrations between 1 and 100 MUM is of a non-genomic nature.

PMID- 21187462
TI  - Experimental model and immunohistochemical comparison of U87 human glioblastoma
      cell xenografts on the chicken chorioallantoic membrane and in rat brains.
AB  - BACKGROUND: To study the neuropathology and selected tumour markers of malignant
      gliomas, an animal glioma model was developed using the implantation of U87 human
      glioblastoma cells into chick chorioallantoic membrane. The immunohistochemical
      characteristics were studied and compared with an orthotopic rodent model.
      MATERIALS AND METHODS: The U87 cell suspension was inoculated onto the chick
      chorioallantoic membrane on embryonic day seven and into the brain of nude rats.
      Brain tumour sections were examined for various known tumour markers by routine
      haematoxylin and eosin staining and immunohistochemical analyses. RESULTS: The
      immunohistochemical analyses showed that S100 protein, glial fibrillary acidic
      protein and synaptophysin expressions, initially present in tissue culture, were
      lost in both models. Persistent kallikrein, CD68 and vimentin expressions in U87
      cells, as well as in both animal tumour models, were detected. The percentage of
      p53-positive nuclei, which was higher in the tumours grown on the chick
      chorioallantoic membrane than in rats, did not correlate with the Ki-67 labelling
      index. Strong cathepsin expression was maintained from the cell culture to both
      tumour models. CD3-positive cells and numerous leukocytes, but no CD20-positive
      cells were detected in any of the animal samples, indicating the immunological
      response of the host to be primarily cellular. Stronger immune reaction for
      vascular endothelial growth factor in rats correlated with an observed increase
      in vascular proliferation in these tumours. CONCLUSION: A simple, fast-growing,
      cheap and well-defined chick chorioallantoic membrane model of glioma was
      established, providing a basis for further experimental studies of genetic and
      protein expression during human glioma tumourigenesis. This model may possibly
      replace some rodent models for selective studies.

PMID- 21187461
TI  - Inhibitory effect of somatostatin Peptide analogues on DNA polymerase activity
      and human cancer cell proliferation.
AB  - BACKGROUND AND OBJECTIVES: It was previously reported that ten small peptides
      derived from TT-232, somatostatin structural analogue (compounds 1-10),
      synthesised by a solution-phase method, exhibited potent antitumour activity on
      human epithelial tumour (A431) cells. MATERIALS AND METHODS: The present study
      investigated the inhibitory activity of these peptide compounds against DNA
      polymerase (pol) and human cancer cell growth. RESULTS: Among the compounds
      tested, compounds 1-5, which contain a t-butyloxycarbonyl (Boc) group, inhibited
      the activity of mammalian pols. Compounds 2 (Boc-Tyr-D-Trp-1-adamantylamide) and
      3 (Boc-Tyr-D-Trp-2-adamantylamide) strongly suppressed the growth of a human
      colon carcinoma (HCT116) cell line and also arrested HCT116 cells in S phase,
      suggesting that these phenomena observed in cancer cells may be due to the
      selective inhibition of mammalian pols, especially DNA replicative pol alpha, by
      these compounds. Compound 2 induced apoptosis of the cells, although compound 3
      did not. CONCLUSION: Compounds 2 and 3 had an enhanced anticancer effect based on
      pol inhibition.

PMID- 21187463
TI  - Interrelationship between protein phosphatase 1 and TGF-{beta} in regulating
      motility and cytoskeletal architecture of endothelial cells.
AB  - Motility of endothelial cells is a requirement for the vascularization of solid
      malignancies. While tumors have been shown to produce a host of angiogenic
      factors, including TGF-beta, the mechanisms by which such factors regulate
      endothelial cell motility have not yet been defined. Thus, the role of the
      serine/threonine phosphatase PP-1 in regulating endothelial cell motility and
      cytoskeletal architecture was studied. The present study demonstrated that TGF
      beta stimulation of motility is dependent on PP-1. Likewise, TGF-beta was shown
      to up-regulate paxillin expression through a process that was PP-1 dependent. The
      interplay between PP-1 and TGF-beta was further observed by the induction of cell
      rounding and the loss of paxillin-actin co precipitations upon PP-1 inhibition
      and the compensation for these effects by TGF-beta. Studies initiated to
      determine how PP-1 might regulate motility showed its role in maintaining
      cytoskeletal organization and its capacity to directly dephosphorylate the focal
      adhesion scaffolding protein paxillin. These studies suggest that the interplay
      between TGF-beta and PP-1 regulates the motility of endothelial cells that is
      critical to the process of angiogenesis.

PMID- 21187464
TI  - Biological activity of hydantoin derivatives on P-glycoprotein (ABCB1) of mouse
      lymphoma cells.
AB  - BACKGROUND: Hydantoin derivatives possess a variety of biochemical and
      pharmacological properties. Although hydantoin compounds are studied extensively,
      there are not many studies that investigate their anticancer properties.
      MATERIALS AND METHODS: Thirty hydantoin compounds were evaluated for their efflux
      modulating effects in cancer cells using a rhodamine 123 accumulation assay and
      real-time fluorometry based on the intracellular accumulation of ethidium
      bromide. RESULTS: The 30 derivatives were screened by real-time fluorometry for
      rhodamine 123 accumulation. Among the selected derivatives, compounds SZ-7, LL-9,
      BS-1, MN-3, P3, RW-15b, AD-26, RW-13, AD-29 and KF-2 significantly increased the
      retention of rhodamine 123. Compounds AD-26, AD-29, RW-13, KF-2, BS-1, MN-3, RW
      15b and JH-63 showed synergistic effect with doxorubicin on mouse lymphoma cells.
      Furthermore, compound SZ-7 had indifferent effect with doxorubicin. CONCLUSION:
      These results indicated the role of chemical modifications within the hydantoin
      ring for its potential inhibition of the ABCB1 transporter. The most active
      structures contained aromatic substituents as well as some tertiary amine
      fragments.

PMID- 21187465
TI  - Cancer chemopreventive potential of aromathecins and phenazines, novel natural
      product derivatives.
AB  - In the search for agents with cancer chemopreventive potential, 14-chloromethyl
      12H-5,11a-diazadibenzo[b,h]fluoren-11-one (compound 1), originally synthesized as
      a potential topoisomerase I inhibitor, and 2,4-dibromo-1-hydroxyphenazine
      (compound 2), an analog of a substance found in the marine bacteria Streptomyces
      CNS284, were found to significantly enhance NADP(H):quinone oxidoreductase 1
      (QR1), glutathione S-transferase (GST), and glutathione (GSH) levels in cell
      culture. However, following a short-term absorption study, analyses of livers
      from the treatment groups did not reveal a significant increase in QR1 or GST
      activity, or GSH levels. This was consistent with RT-PCR analyses of tissue
      samples. The compounds were absorbed, as judged by LC/MS analyses of serum and
      tissue samples, although levels were well below the concentrations required to
      mediate in vitro responses. Metabolites of compound 2 formed in vitro by human
      liver microzones were characterized using high resolution tandem mass
      spectrometry. In sum, the in vivo activity of these compounds appears to be
      diminished by low bioavailability, but this experimental approach indicates the
      importance of systematic biomarker investigation.

PMID- 21187466
TI  - Influence of novel KGFR tyrosine kinase inhibitors on KGF-mediated proliferation
      of breast cancer.
AB  - BACKGROUND: Keratinocyte growth factor (KGF) acts at the KGF receptor (KGFR) to
      produce a rapid stimulation of breast cancer cell proliferation and motility
      which is mediated via the Erk signaling pathway. Enhancement of KGF/KGFR signal
      transduction may be an early step in the metastatic progression of breast cancer.
      Receptor modeling of KGFR was used to identify selective KGFR tyrosine kinase
      (TK) inhibitor molecules that have the potential to bind selectively to the KGFR.
      The present study evaluated the biological activity of 57 of these KGFR TK
      inhibitor compounds on breast cancer cells. MATERIALS AND METHODS: These
      compounds were tested for their ability to inhibit KGF-mediated breast cancer
      cell proliferation in MCF-7 breast cancer cells. Furthermore, the effects of the
      most effective proliferation inhibitors were examined on Erk signaling and on the
      relative density of cell membrane KGFR. RESULTS: It was observed that 27 of the
      57 compounds tested produced a 20% or greater reduction in KGF-mediated
      proliferation; while five compounds produced greater than 50% inhibition. In
      addition, the most potent inhibitors also reduced Erk signaling and cell membrane
      density of the KGFR. CONCLUSION: The compounds examined appear to be selective
      KGFR inhibitors which inhibit KGF-mediated activity and reduce the expression of
      KGFR on cancer cells. These results may lead to the development of a novel class
      of anticancer agents for the prevention of metastatic cancer progression.

PMID- 21187467
TI  - Cytotoxicity and antileukaemic activity of new duplexes linking 3-C
      ethynylcytidine and 5-fluorodeoxyuridine.
AB  - The cytotoxic and antineoplastic potential of two new duplex drugs, ECyd-5-FdU
      and ECyd- lipid- 5-FdU, were compared with the activity of the parent single
      nucleoside analogues, 3-C-ethynylcytidine (ECyd) and 5-fluorodeoxyuridine (5
      FdU), either applied as monotherapy or simultaneously in equimolar concentrations
      simulating their ratio in a duplex drug. Murine leukaemia L1210 cells were used
      for comparative in vitro tests of the duplex and the single drugs. The tested
      substances were evaluated for their cytotoxicity, combinatory potential and
      revitalisation properties. Additionally, an in vivo model of leukaemia L1210
      bearing mice of the DBA/2J strain was used for testing of acute toxicity and
      antileukaemic activity using various chemotherapeutic regimes. Based on the
      results of this study, the suitability of ECyd and 5-FdU for forming a duplex
      drug was discussed from the perspective of their expected synergistic anticancer
      activities. We found an improvement of chemotherapy outcomes of the new duplex
      drugs tested by comparing their in vitro cytotoxicity and an increase of the time
      of survival of experimental leukaemia-bearing mice in a statistically significant
      manner.

PMID- 21187468
TI  - Tumour response to gefitinib is associated with EGF- and gefitinib- but not
      radiation-modulated EGFR expression.
AB  - AIM: This study was conducted to explore the relationship between different
      treatment-modulated EGFR expression and gefitinib sensitivity. MATERIALS AND
      METHODS: Gefitinib-sensitive (A431) and -resistant (A375, MALME-3M, and SK-MEL 5)
      tumour cell lines were treated with epidermal growth factor (EGF), gefitinib or
      radiation in vitro, and EGFR expression levels were measured by using ELISA.
      RESULTS: EGF, and gefitinib treatment resulted in significantly higher levels of
      total and/or phosphorylated EGFR in sensitive than in resistant tumours and this
      was associated with gefitinib IC(50). In contrast, radiation-modulated EGFR
      expression, both total and phosphorylated, did not correlate with the efficacy of
      gefitinib. Stimulation of proliferation by EGF was significantly stronger in A431
      than in the other three lines, indicating sensitive tumours were more EGFR
      dependent than resistant tumours for cell proliferation. CONCLUSION: These
      findings imply a potential role of EGF- and gefitinib-modulated EGFR expression
      in predicting gefitinib sensitivity.

PMID- 21187469
TI  - Gender differences in gemcitabine (Gemzar) efficacy in cancer cells: effect of
      indole-3-carbinol.
AB  - Pancreatic cancer has a poor prognosis, mainly due to lack of effective
      therapies. This study demonstrated the ability of dietary agent, indole-3
      carbinol (I3C), to lower the LD(50) of gemcitabine (Gemzar) in decreasing growth
      of both male (MiaPaca2) and female (SU86.86) pancreatic cancer cells. Female
      pancreatic cancer cells were more resistant to gemcitabine alone. Additionally,
      RT-PCR analysis of MiaPaca2 cells treated with 1, 10 or 100 MUM of I3C showed
      that I3C reactivated the tumor suppressor gene p16INK4a in pancreatic cancer
      cells. Methylated-specific PCR analysis indicated that I3C demethylated the
      promoter region of p16 INK4a, which was methylated in the untreated cancer cells.
      p16INK4a inactivation through promoter hypermethylation is considered an early
      event in pancreatic carcinogenesis. A positive control using 5-azacytidine also
      reactivated p16INK4a. This study demonstrated the potential of I3C, a possible
      non-toxic hypomethylating agent, combined with the anticancer agent, gemcitabine,
      to be a powerful strategy for treating pancreatic cancer.

PMID- 21187470
TI  - All-trans retinoic acid modulates cancer stem cells of glioblastoma multiforme in
      an MAPK-dependent manner.
AB  - Glioblastoma multiforme (GBM), a grade IV glioma, appears to harbor therapy
      resistant cancer stem cells (CSCs) that are the major cause of recurrence. All
      trans retinoic acid (ATRA), a derivative of retinoid, is capable of
      differentiating a variety of stem cells, as well as normal neural progenitor
      cells, and down-regulates expression of the stem cell marker nestin. This study
      investigated the effects of ATRA on differentiation, proliferation, self-renewal,
      and signaling pathways of CSCs in GBM. CSCs differentiated into glial and
      neuronal lineages at low concentrations of ATRA (10 MUM). Proliferation and self
      renewal of neurospheres were reduced following ATRA, although ATRA induced
      apopotsis at higher (40 MUM) concentrations. Analysis of mitogen-activated
      protein kinase signaling pathways, specifically extracellular signal-regulated
      kinases (ERK1/2), showed that ATRA-induced alterations in ERK1/2 were associated
      with regulation of differentiation, proliferation and apoptosis. These results
      emphasize that low doses of ATRA may have therapeutic potential by
      differentiating GBM CSCs and rendering them sensitive to targeted therapy.

PMID- 21187471
TI  - Progesterone receptor antagonist therapy has therapeutic potential even in cancer
      restricted to males as evidenced from murine testicular and prostate cancer
      studies.
AB  - BACKGROUND: Treatment with the progesterone receptor antagonist mifepristone has
      been shown to improve the length and quality of life in mice with spontaneous
      leukemia, breast cancer, and lung cancer. The present study evaluated the
      efficacy of mifepristone therapy in murine tumors restricted to males, i.e.
      testicular and prostate cancer. MATERIALS AND METHODS: Eight-week-old mice with a
      strong predisposition to testicular or prostate cancer were gavaged with
      mifepristone. Olive oil was used in place of mifepristone in order to provide a
      control. Survival rates and body conditioning scores were compared after one year
      of treatment. RESULTS: Non-significant trends in survival rates were found in
      both types of murine cancers. Mifepristone significantly reduced the number of
      sick days in mice with testicular cancer. There was a significant reduction of
      adverse events (i.e. a tumor >1 cm or bleeding from the penis) in those with
      prostate cancer treated with mifepristone. CONCLUSION: These data support the
      hypothesis that various cancers may utilize a mechanism that is present in normal
      pregnancy that involves secretion of a progesterone-induced protein that blocks
      natural killer cell activity. The hypothesis that the cancer cells have the
      capacity to direct local progesterone production is supported by demonstrating
      the benefit of a progesterone receptor antagonist in tumors restricted to males.

PMID- 21187472
TI  - Targeting KRAS mutation-bearing lung cancer in vivo by pulmonary surfactant
      adenovirus-mediated gene transfer.
AB  - Pulmonary surfactant has been used as a carrier to deliver a therapeutic virus to
      dysfunctional lung cells that reside within an intricate lung structure. To
      investigate whether pulmonary surfactant enhances the efficacy of intratracheal
      instillation of a therapeutic virus to target KRAS mutation-bearing lung cancer
      in vivo, we developed a recombinant adenovirus that induces cell death only in
      lung cancer cells and injected the adenovirus into a mouse model of KRAS mutation
      positive lung cancer intratracheally with and without surfactant. A therapeutic
      adenovirus that induces cell death only in lung cancer cells was constructed by
      combining a cancer-specific human telomerase reverse transcriptase (hTERT)
      promoter fused to CCAAT/enhancer-binding protein alpha (CEBPalpha) with a
      modified lung-specific Clara cell-specific 10-kDa protein (CC10) promoter fused
      to cytotoxic adenovirus type 5 early region 1A (E1A). CEBPalpha is induced only
      in cancer cells and activates the CC10 promoter, which in turn induces cytotoxic
      E1A, and causes cell death only in lung cancer cells in vitro. This adenovirus
      was intratracheally administered to the model mice (CCSP-rtTA/Tet-op-K-Ras4bG12D
      bitransgenic mice) in the presence and absence of pulmonary surfactant.
      Intratracheally administered therapeutic adenovirus with pulmonary surfactant
      spread to airways, as well as to the alveolar region of the lung, and caused a
      reduction of lung tumors developed. The therapeutic adenovirus without pulmonary
      surfactant spread only to airways and was ten-fold less effective in tumor
      reduction. Here, we demonstrate that pulmonary surfactant is an efficient tool to
      intratracheally deliver a therapeutic virus to treat KRAS mutation-positive lung
      cancer in vivo.

PMID- 21187473
TI  - d-delta-Tocotrienol-mediated cell cycle arrest and apoptosis in human melanoma
      cells.
AB  - BACKGROUND: The rate-limiting enzyme of the mevalonate pathway, 3-hydroxy-3
      methylglutaryl coenzyme A (HMG CoA) reductase, provides essential intermediates
      for the prenylation or dolichylation of growth-related proteins. d-delta
      tocotrienol, a post-transcriptional down-regulator of HMG CoA reductase,
      suppresses the proliferation of murine B16 melanoma cells. Dietary d-delta
      tocotrienol suppresses the growth of implanted B16 melanomas without toxicity to
      host mice. MATERIALS AND METHODS: The proliferation of human A2058 and A375
      melanoma cells following a 72 h incubation in 96-well plates was measured by
      CellTiter 96(r) Aqueous One Solution. Cell cycle distribution was determined by
      flow cytometry. Fluorescence microscopy following acridine orange and ethidium
      bromide dual staining and procaspase-3 cleavage were used to detect apoptosis.
      Western-blot was employed to measure protein expression. RESULTS: d-delta
      Tocotrienol induced dose-dependent suppression of cell proliferation with 50%
      inhibitory concentrations (IC(50)) of 37.5 +/- 1.4 (A2058) and 22.3 +/- 1.8
      (A375) MUmol/l, respectively (data are reported as mean +/- standard deviation).
      d-delta-Tocotrienol-mediated cell cycle arrest at the G(1) phase was accompanied
      by reduced expression of cyclin-dependent kinase 4. Concomitantly, d-delta
      tocotrienol induced caspase-3 activation and apoptosis. The impact of d-delta
      tocotrienol on A2058 cell proliferation was potentiated by lovastatin (IC(50)=3.1
      +/- 0.5 MUmol/l), a competitive inhibitor of HMG CoA reductase. CONCLUSION: d
      delta-Tocotrienol may have potential application in melanoma chemoprevention
      and/or therapy.

PMID- 21187474
TI  - Comparison of metallothionein (MT) and Ki-67 antigen expression in benign and
      malignant thyroid tumours.
AB  - Thyroid carcinomas are the most frequently occurring tumours in the endocrine
      system. Metallothioneins (MT) and Ki-67 proteins are present in intensely
      proliferating cells, and their expression has been observed in numerous tumours,
      including thyroid tumours. The purpose of this study was to analyse the
      relationship between intensity of MT expression and Ki-67 antigen on one hand and
      histological features of the examined thyroid tumours on the other. The
      investigated material included 186 archival paraffin blocks with samples of
      various thyroid tissues, obtained from the Chair and Department of
      Pathomorphology, Medical University of Wroclaw. In paraffin sections,
      immunohistochemical reactions were performed with the use of monoclonal anti-MT
      (I/II) and anti-Ki-67 antibodies. Intensity of MT and Ki-67 antigen expression
      was evaluated using a light microscope using the semi-quantitative method of
      Remmele. A significant difference in MT expression was noted between different
      tumours of the thyroid: the highest expression was detected in follicular
      carcinoma and the lowest was detected in medullary carcinoma. Expression of MT
      was also significantly elevated in follicular carcinoma as compared to follicular
      adenoma. On the other hand, no significant differences were seen between
      expression of Ki-67 antigen in follicular adenoma and follicular carcinoma.
      Moreover, these investigations detected no correlation between the expression of
      MT and Ki-67 antigen in follicular adenoma and follicular carcinoma. In view of
      the obtained results, the expression of MT can be considered as a potential
      marker of differentiation between the two types of thyroid tumours, which are
      otherwise difficult to differentiate.

PMID- 21187475
TI  - PI-103 and sorafenib inhibit hepatocellular carcinoma cell proliferation by
      blocking Ras/Raf/MAPK and PI3K/AKT/mTOR pathways.
AB  - BACKGROUND: Aberrant Ras/Raf/MAPK and PI3K/AKT/mTOR signaling pathways are found
      in hepatocellular carcinoma (HCC). This study reports how sorafenib (a multi
      kinase inhibitor) and PI-103 (a dual PI3K/mTOR inhibitor) alone and in
      combination inhibit the proliferation of the HCC cell line, Huh7. MATERIALS AND
      METHODS: Huh7 proliferation was assayed by 3H-thymidine incorporation and by MTT
      assay. Western blot was used to detect phosphorylation of the key enzymes in the
      Ras/Raf and PI3K pathways. RESULTS: Sorafenib and PI-103, as single agents
      inhibited Huh7 proliferation and epidermal growth factor (EGF)-stimulated Huh7
      proliferation in a dose-dependent fashion; the combination of sorafenib and PI
      103 produced synergistic effects. EGF increased phosphorylation of MEK and ERK,
      key Ras/Raf downstream signaling proteins; this activation was inhibited by
      sorafenib. However, sorafenib as a single agent increased AKT(Ser473) and mTOR
      phosphorylation. EGF-stimulated activation of PI3K/AKT/mTOR pathway components
      was inhibited by PI-103. PI-103 is a potent inhibitor of AKT(Ser473)
      phosphorylation; in contrast, rapamycin stimulated AKT(Ser473) phosphorylation.
      It was found that PI-103, as a single agent, stimulated MEK and ERK
      phosphorylation. However, the combination of sorafenib and PI-103 caused
      inhibition of all the tested kinases in the Ras/Raf and PI3K pathways.
      CONCLUSION: The combination of sorafenib and PI-103 can significantly inhibit EGF
      stimulated Huh7 proliferation by blocking both Ras/Raf/MAPK and PI3K/AKT/mTOR
      pathways.

PMID- 21187476
TI  - Alternative lengthening of telomeres as a prognostic factor in malignant fibrous
      histiocytomas of bone.
AB  - BACKGROUND: Malignant fibrous histiocytoma (MFH) of bone is a rare primary
      malignant neoplasm. Recent studies indicate a positive correlation between the
      telomere maintenance mechanism and tumour aggressiveness in sarcomas. This study
      was undertaken to analyse the clinical significance of telomere factors in
      primary tumour samples from patients with MFHs of bone. MATERIALS AND METHODS:
      Telomerase activity was measured in ten bone MFH specimens using a PCR-based TRAP
      assay. Telomere length was assessed using gel hybridisation. Quantitative
      detection of human telomerase reverse transcriptase (hTERT) was performed by real
      time PCR. RESULTS: Telomerase activity and hTERT expression were detectable in
      100% of tumour samples and 50% of tumour samples had evidence of engagement of
      the alternative lengthening of telomere (ALT) mechanisms. ALT was a significant
      prognostic risk factor (p = 0.0316). CONCLUSION: This study suggests that the
      presence of ALT telomere maintenance mechanisms indicates a poor prognosis for
      bone MFH patients.

PMID- 21187477
TI  - Base excision repair activities differ in human lung cancer cells and
      corresponding normal controls.
AB  - Oxidative damage to DNA is thought to play a role in carcinogenesis by causing
      mutations, and indeed accumulation of oxidized DNA bases has been observed in
      samples obtained from tumors but not from surrounding tissue within the same
      patient. Base excision repair (BER) is the main pathway for the repair of
      oxidized modifications both in nuclear and mitochondrial DNA. In order to
      ascertain whether diminished BER capacity might account for increased levels of
      oxidative DNA damage in cancer cells, the activities of BER enzymes in three
      different lung cancer cell lines and their non-cancerous counterparts were
      measured using oligonucleotide substrates with single DNA lesions to assess
      specific BER enzymes. The activities of four BER enzymes, OGG1, NTH1, UDG and
      APE1, were compared in mitochondrial and nuclear extracts. For each specific
      lesion, the repair activities were similar among the three cell lines used.
      However, the specific activities and cancer versus control comparison differed
      significantly between the nuclear and mitochondrial compartments. OGG1 activity,
      as measured by 8-oxodA incision, was up-regulated in cancer cell mitochondria but
      down-regulated in the nucleus when compared to control cells. Similarly, NTH1
      activity was also up-regulated in mitochondrial extracts from cancer cells but
      did not change significantly in the nucleus. Together, these results support the
      idea that alterations in BER capacity are associated with carcinogenesis.

PMID- 21187478
TI  - Phosphorylation of TCTP as a marker for polo-like kinase-1 activity in vivo.
AB  - Polo-like kinase 1 (PLK1) is the master regulator of mitosis and a target for
      anticancer therapy. To develop a marker of PLK1 activity in cells and tumour
      tissues, this study focused on translational controlled tumour protein (TCTP) and
      identified serine 46 as a site phosphorylated by PLK1 in vitro. Using an antibody
      raised against phospho-TCTP-Ser46, it was demonstrated that phosphorylation at
      this site correlates with PLK1 level and kinase activity in cells. Moreover, PLK1
      depletion by siRNA or inactivation by specific inhibitors caused a correspondent
      decrease in phospho-TCTP-Ser46 signal validating this site as a direct marker of
      PLK1. Using this marker, the study characterized PLK1 inhibitors in cells by
      setting up a high-content assay and finally immunohistochemical assay suitable
      for following inhibitor activity in preclinical tumour models and possibly in
      clinical studies was developed.

PMID- 21187479
TI  - The effects of anti-VEGFR and anti-EGFR agents on glioma cell migration through
      implication of growth factors with integrins.
AB  - OBJECTIVE: The aim of this study was to assess the antitumour effect of an anti
      VEGFR (sunitinib) and the anti-EGFR multi-targeted agent (lapatinib), applied
      either alone or in combination on the migration capacity of two glioma cell
      lines. Furthermore, this study sought to evaluate the effect of lapatinib in the
      formation of EGFR-integrin beta(1) complex, as well as the effect of sunitinib in
      the VEGFR-integrin beta(3) and PDGFR-integrin beta(3) complexes formation.
      MATERIALS AND METHODS: U87 and M059K cells were cultured as recommended by the
      American Type Culture Collection (ATCC). Migration assays were performed in
      Boyden chambers, using uncoated polycarbonate membranes. Immunoprecipitation and
      Western blot analysis were used for studying the complex formation of EGFR, PDGFR
      and VEGFR with integrins. The protein localisation was evaluated using
      immunofluorescence assay. RESULTS: It was found that both agents, administered
      either alone or in combination, reduced the ability of U87 and M059K cells to
      migrate four h after their application. The time course study of the effect of
      lapatinib on EGFR-integrin beta(1) complex revealed an inhibition in complex
      formation up to 30 min after the application of the agent. Likewise, sunitinib
      inhibited complex formation of VEGFR-integrin beta(3) complex within two h after
      its application without affecting PDGFR-integrin beta(3) complex. The previously
      described interruption of complexes formation was confirmed with an
      immunofluorescence assay. CONCLUSION: The preliminary results of this study are
      the first to support the implication of a dual anti-EGFR/HER-2 agent, lapatinib
      and a multi-targeted agent, sunitinib in glioma cell migration, through a
      mechanism implying interruption of growth factor receptor integrin complexes
      formation.

PMID- 21187480
TI  - E-cadherin and alpha-catenin expression in normal, hyperplastic and neoplastic
      endometrium.
AB  - The aim of this study was to determine whether modulation of expression of cell
      adhesion molecules may occur in neoplastic transformation of endometrial
      epithelium. MATERIALS AND METHODS: E-Cadherin and alpha-catenin protein
      expression were evaluated by immunohistochemistry in 124 biopsies representative
      of normal, hyperplastic and neoplastic endometrium. RESULTS: In normal
      endometrium (proliferative, secretive and atrophic endometrium) strong
      homogeneous, E-cadherin and alpha-catenin reactivity was found; 58.3% and 66.6%
      of biopsies representative of simple hyperplastic endometrium were homogeneously
      positive for E-cadherin and alpha-catenin, respectively, whereas no samples
      representative of atypical hyperplasia showed evidence of homogeneous E-cadherin
      or alpha-catenin expression. No expression of homogeneous E-cadherin was seen in
      endometrial adenocarcinomas; alpha-catenin homogeneous immunostaining was
      observed in 2 G1 and 2 G2 out of 22 adenocarcinoma samples (18.2%). A homogeneous
      co-expression of both molecules was seen only in normal (70%) and simple
      hyperplastic (46%) endometrium. CONCLUSION: These results suggest that E-cadherin
      and alpha-catenin down-regulation might be associated with neoplastic
      transformation of endometrial tissues.

PMID- 21187482
TI  - Down-regulation of Mus81 as a potential marker for the malignancy of gastric
      cancer.
AB  - BACKGROUND: The Mus81 gene encodes a critical endonuclease involved in DNA repair
      and tumor suppression. In the present study, the role of Mus81 in gastric cancer
      was explored. MATERIALS AND METHODS: Mus81 expression in 53 cases of gastric
      cancer and the corresponding normal tissues was determined by quantitative real
      time PCR. The correlations between Mus81 down-regulation and the
      clinicopathological data were also evaluated. RESULTS: Mus81 expression was
      significantly lower in gastric cancer tissues than the corresponding normal
      tissues (p = 0.018) and the down-regulation of Mus81 occurred in 51% (27/53) of
      the gastric carcinomas. More importantly, Mus81 down-regulation correlated
      significantly to invasion depth (p = 0.015) and poorly-differentiated type (p =
      0.016) of gastric cancer. CONCLUSION: Mus81 might be a potential marker for the
      malignancy of gastric cancer.

PMID- 21187481
TI  - Gamma-secretase complexes regulate the responses of human pancreatic ductal
      adenocarcinoma cells to taxanes.
AB  - BACKGROUND/AIM: It was previously reported that gamma-secretase inhibitors (GSIs)
      enhance taxane-induced mitotic arrest and apoptosis in colon cancer cells. To
      enable the development of taxane-based chemotherapy for pancreatic ductal
      adenocarcinoma (PDAC), this study investigated the molecular mechanisms by which
      gamma-secretase (GS) complexes regulate taxane sensitivity. MATERIALS AND
      METHODS: The effect of GS complexes on taxane-induced apoptosis in PDAC cells was
      evaluated by a cell cycle analysis. GS complexes were examined with small
      interference RNAs targeted to GS complex-related genes. RESULTS: GSIs and
      silencing of presenilin 1 (PS1) did not affect cell proliferation but resulted in
      enhanced taxane-induced G(2)/M accumulation and apoptosis. Silencing of the Notch
      gene did not induce these effects. However, PS2-specific silencing suppressed
      proliferation and taxane-induced apoptosis. CONCLUSION: Data from this study
      indicate that GS complexes regulate the response of PDAC to taxanes through GS
      dependent and GS-independent mechanisms.

PMID- 21187483
TI  - Detection of vimentin (VIM) methylation in the serum of colorectal cancer
      patients.
AB  - AIM: Detection of colorectal cancer using serum assay of vimentin methylation.
      MATERIALS AND METHODS: We attempted to detect vimentin methylation in the serum
      of colorectal cancer patients using quantitative methylation-specific polymerase
      chain reaction (qMSP). RESULTS: Of 44 colorectal cancer patients, 4 (9%)
      exhibited methylation of the vimentin gene in their serum DNA by qMSP.
      Interestingly, methylation was significantly found in the serum of patients with
      liver metastasis, peritoneal dissemination, and distant metastasis (p = 0.026, p
      = 0.0029 and p = 0.0063, respectively), suggesting that vimentin methylation in
      serum might be detected more frequently in patients with advanced colorectal
      cancer. CONCLUSION: The high sensitivity of qMSP makes it possible to detect
      smaller amounts of tumor DNA in the serum, suggesting that qMSP can be used as a
      screening method for cancer.

PMID- 21187484
TI  - Suppression of tumour metastasis in a murine osteosarcoma model with anti-CD25
      monoclonal antibody treatment.
AB  - BACKGROUND: Mouse regulatory T cells (Treg) may be deleted by intraperitoneal
      injection of anti-CD25 monoclonal antibody (mAb) (PC61). When Treg populations
      are thus suppressed, the immune system attacks tumours in autoimmune reactions.
      MATERIALS AND METHODS: An osteosarcoma (LM8) was transplanted subcutaneously into
      C3H/He mice. Serial injections of PC61 were conducted from seven days before (pre
      PC61 group) or from two days thereafter (post-PC61 group) and tumour growth and
      metastasis were examined four weeks later. A control group received PBS
      injections. RESULTS: Subcutaneous tumours were reduced in size and the numbers of
      lung and liver metastatic colonies were significantly decreased in both pre- and
      post-PC61 groups compared to the control group. CONCLUSION: Tumour suppression
      was effective even when injection of PC61 was performed two days after LM8
      transplantation. These results indicate that such treatments might be suitable to
      be applied in the clinic after surgical operations.

PMID- 21187485
TI  - Cancer/Testis antigen expression on mesenchymal stem cells isolated from
      different tissues.
AB  - BACKGROUND/AIMS: The expression of cancer/testis antigens (CTAs) on additional
      normal tissues or stem cells may restrict their use as cancer targets. The
      objective of the present study was to evaluate the mRNA levels of some CTAs in a
      variety of tissues. MATERIALS AND METHODS: mRNA of pericytes, fibroblasts and
      mesenchymal stem cells (MSCs) derived from adult and fetal tissues, human
      umbilical vein endothelial cells, MSC-derived adipocytes, selected normal tissues
      and control cancer cell lines (CLs) were extracted and quantitative polymerase
      chain reaction was performed for MAGED1, PRAME, CTAG1B, MAGEA3 and MAGEA4.
      RESULTS: MAGED1 was expressed in all normal tissues and cells evaluated. CTAG1B
      was expressed at levels comparable to control CLs on MSCs derived from arterial,
      fetal skin, adipose tissue and saphenous vein, heart, brain and skin tissues.
      MAGEA4 was detected only in fibroblasts and differentiated adipocytes from MSCs,
      at levels comparable to the control CLs. CONCLUSION: The potential use of CTAs in
      immunotherapy should take into account the potential off-target effects on MSCs.

PMID- 21187486
TI  - Parathyroid hormone-related peptide regulates matrix metalloproteinase-13 gene
      expression in bone metastatic breast cancer cells.
AB  - BACKGROUND: Breast cancer (BC) cells often metastasize to bone where they express
      large amounts of parathyroid hormone-related protein (PTHrP). In this study, we
      investigated the possibility that PTHrP may have roles in breast cancer bone
      metastasis independently of, or in addition to, its roles in osteoclastic
      function. MATERIALS AND METHODS: A mouse model of bone metastasis was prepared by
      inoculating mice with suspensions of the human BC cell line MDA-MB-231 tumor
      cells via the left cardiac ventricle. Matrix metalloproteinase-13 (MMP-13)
      expression in the bone microenvironment was examined by Western blot and Real
      time RT-PCR (RT-PCR) analysis, as well as by confocal microscopy. RESULTS: The
      invading MDA-MB-231 cells contained conspicuous amounts of both PTHrP and MMP-13,
      an important matrix-degrading enzyme; and treatment of the cells in culture with
      exogenous PTHrP markedly stimulated MMP13 gene expression. Analysis of signaling
      mechanisms showed that PTHrP treatment led to rapid increases in the levels of
      phosphorylated protein kinase C (PKCalpha) and extracellular signal-regulated
      kinase (ERK1/2). Pharmacologic inhibition of ERK1/2 and PKC as well as of PKA
      activities counteracted the PTHrP-dependent stimulation of MMP13 expression.
      Indeed, pharmacologic activation of PKA or PKC was sufficient for stimulation of
      MMP13 expression. CONCLUSION: Consistent with these findings, the inhibition of
      PKC prevented PTHrP-induced activation of ERK1/2, whereas 12-O
      tetradecanoylphorbol-13-acetate (TPA), a stimulator of PKC, up-regulated the
      PTHrP-induced activation of ERK1/2. Taken together, our data indicate that the
      MDA-MB-231 breast cancer cells may carry out bone destruction and favor their own
      metastatic behavior by producing MMP-13. Given that the cells expressed PTHrP and
      that this factor stimulated MMP-13 expression, metastatic bone destruction may
      result from a PTHrP autocrine loop involving a PKC-ERK1/2 signaling pathway.

PMID- 21187487
TI  - Corticorelin acetate, a synthetic corticotropin-releasing factor with preclinical
      antitumor activity, alone and with bevacizumab, against human brain tumor models.
AB  - BACKGROUND: Corticorelin acetate (CrA) is a synthetic form of corticotropin
      releasing factor that is currently undergoing clinical trials in the treatment of
      peritumoral brain edema (PBE). This study preclinically investigated its
      potential as an antitumor agent against human brain tumor xenografts. MATERIALS
      AND METHODS: The in vivo efficacy of CrA as a single agent and in combination
      with the antiangiogenic agent, bevacizumab, was examined in three different
      patient-derived human brain tumor xenografts implanted orthotopically
      (intracranially) or subcutaneously in athymic mice. RESULTS: CrA significantly
      increased the lifespan of mice implanted orthotopically with two different
      pediatric brain tumor xenograft models. In one of these tumor models, the
      combination of CrA with bevacizumab produced a therapeutic outcome superior to
      that found using either of the two agents alone. CONCLUSION: The application of
      CrA for the treatment of PBE likely involves its activity as an anti-angiogenic
      agent, which may be one possible mechanism to explain its observed preclinical
      antitumor activity against orthotopic human brain tumor models. Additional
      studies to investigate other possible mechanisms of action are underway.

PMID- 21187488
TI  - High-mobility group B1 (HMGB1) and receptor for advanced glycation end-products
      (RAGE) expression in canine lymphoma.
AB  - BACKGROUND: Canine lymphoma is a commonly occurring, spontaneously developing
      neoplasia similar to human non-Hodgkin's lymphoma and, thus, is used as a
      valuable model for human malignancy. HMGB1 and RAGE are strongly associated with
      tumour progression and vascularisation. Consequently, deregulated RAGE and HMGB1
      may play an important role in the mechanisms involved in lymphoma progression.
      MATERIALS AND METHODS: Expression patterns of HMGB1 and RAGE were analysed in 22
      canine lymphoma and three canine non-neoplastic control samples via real time PCR
      and canine beta-glucuronidase gene (GUSB) as endogenous control. RESULTS: HMGB1
      was up-regulated in the neoplastic samples, while RAGE expression remained
      inconspicuous. CONCLUSION: This study demonstrated similar mechanisms in lymphoma
      progression in humans and dogs due to overexpression of HMGB1, which was
      described in human lymphomas. RAGE remained stable in terms of expression
      indicating that the extracellular HMGB1-induced effects are regulated by HMGB1
      itself.

PMID- 21187489
TI  - Effects of the synthetic vasopressin analog desmopressin in a mouse model of
      colon cancer.
AB  - Experimental and clinical data indicated that perioperative administration of the
      hemostatic peptide desmopressin (DDAVP) can inhibit progression of residual
      metastatic cells. The compound seems to act by inducing an agonist effect on
      specific V2 vasopressin membrane receptors present in both tumor cells and
      endothelial cells. Here we explored the antitumor effects of DDAVP in cultured
      colon carcinoma cells and in a syngeneic Balb/c mouse model. Both human Colo-205
      and mouse CT-26 colon carcinoma cell lines expressed the V2 receptor, as revealed
      by immunofluorescence. DDAVP (at doses ranging from 100 ng/ml to 1 MUg/ml)
      exerted a modest but significant antiproliferative effect on cultured CT-26 and
      Colo-205 cells. In vivo, DDAVP (2 intravenous doses of 2 MUg/kg) reduced
      accumulation of ascites and formation of intestinal tumor nodules in mice
      intraperitoneally inoculated with CT-26 cells. Perioperative administration of
      DDAVP significantly inhibited tumor progression in animals surgically implanted
      in the spleen with CT-26 cells, and caused some reduction in liver metastasis.
      Although DDAVP and 5-fluorouracil demonstrated additive cytostatic effects in
      vitro, no antitumor effects were observed in this study in mice receiving a
      single cycle of chemotherapy (25 mg/kg) in combination with the peptide. Our data
      suggest that DDAVP may be potentially used to minimize spread or survival of
      residual malignant cells during surgical procedures for colon and other
      gastrointestinal tumors.

PMID- 21187490
TI  - Up-regulation of glypican-3 in human hepatocellular carcinoma.
AB  - AIM: To investigate the expression and significance of glypican-3 (GPC3) in human
      hepatocellular carcinoma (HCC). MATERIALS AND METHODS: DNA chips were used to
      measure the expression of mRNAs for members of the glypican and syndecan families
      of heparan sulfate proteoglycans (HSPGs) in normal liver tissue, non-tumor
      tissues and HCC. GPC3 protein expression was investigated by immunohistochemical
      staining in the tissues samples and Western blotting in human HCC cell lines. In
      addition, the levels of GPC3 protein in the blood were determined by ELISA.
      RESULTS: Only the expression of GPC3 was found to be markedly elevated in HCCs.
      In the human HCC cell lines, GPC3 expression was consistently observed, and was
      mainly located in the cell membrane and cytoplasm. Immunohistochemistry showed a
      tendency for overall staining of the cytoplasm of cells in the liver carcinoma
      tissues, but the cell membrane was preferentially stained in poorly
      differentiated HCC when compared with well-differentiated HCC. Moreover, the cell
      membrane was preferentially stained in metastatic lesions of HCC when compared
      with primary HCC lesions. Non-tumor tissues and cholangiocellular carcinoma
      tissues were not stained. In addition, using HepG2 cells, AG490 and piceatannol,
      which are signal transducer and activator of transcription 3 (STAT3) inhibitors,
      each increased the amount of GPC3 mRNA expressed. Assay of the circulating levels
      of GPC3 protein in chronic liver disease and HCC found that serum GPC3 protein
      levels were significantly elevated in the latter. CONCLUSION: GPC3 is highly
      expressed in HCC, and its expression pattern differs according to the degree of
      cell differentiation. In addition, the expression of GPC3 is regulated by Janus
      kinase-STAT signaling. GPC3 shows potential as a tumor biomarker for HCC that can
      be used for molecularly targeted therapy.

PMID- 21187491
TI  - Activation of the serine/theronine protein kinase Akt in enteropancreatic
      neuroendocrine tumors.
AB  - BACKGROUND: Akt is a regulator of cell proliferation, tumorigenesis and
      apoptosis. This study evaluated the incidence of Akt activation in a subset of
      neuroendocrine tumors (NETs) and its correlation to clinical pathological
      parameters. MATERIALS AND METHODS: A subset of 46 samples from patients with
      enteropancreatic NETs (26 male and 20 female) were selected for evaluation. The
      tissue slides were stained with a mouse monoclonal antiphospho-Akt antibody using
      the avidin-biotin-complex method. RESULTS: The tumors were from the small (n =
      18) and large bowel (n = 9) and from the pancreas (n = 16). Activation of Akt was
      detected in 61% (28/46) of cases. No statistical correlation was found between
      the p-Akt score and tumor grade (p = 0.72), tumor size (p = 0.72) and the
      presence of metastases (p = 0.52). CONCLUSION: This study shows activation of Akt
      in a subset of enteropancreatic NET for the first time. This finding suggests a
      role of p-Akt in NET carcinogenesis.

PMID- 21187492
TI  - Tumor-specific cytotoxicity and type of cell death induced by benzaldehyde.
AB  - We have previously reported that sodium 5,6-benzylidene-L-ascorbate (SBA) induced
      dramatic antitumor activity in inoperable cancer patients, but induced only
      marginal tumor specificity in vitro. Here the tumor specificity and type of cell
      death induced by benzaldehyde (BA), a degradation product of SBA, was
      investigated, using human tumor cell lines (oral squamous cell carcinoma [OSCC],
      glioblastoma, myelogenous leukemia) and human normal oral cells (gingival
      fibroblast, pulp cell, periodontal ligament fibroblast). BA showed much higher
      tumor-specific cytotoxicity than SBA. BA induced the formation of autophagosomes,
      the destruction of mitochondrial structure and digestion of broken organelles,
      without any apparent induction of internucleosomal DNA fragmentation and caspase
      activation in an OSCC cell line HSC-2, in a similar manner to SBA. However,
      pretreatment with 3-methyladenine or bafilomycin A(1), autophagy inhibitors, did
      not completely rescue the cells from the cytotoxicity induced by BA. The study
      suggests that BA may play an important role in the induction of antitumor
      activity of SBA in vivo, although the autophagic phenotypes induced by BA may be
      involved in both cell death and survival.

PMID- 21187493
TI  - Aromatase expression in leptin-pretreated human breast pre-adipocytes is enhanced
      by zeranol and suppressed by (-)-gossypol.
AB  - BACKGROUND: Obesity is associated with an increased risk of estrogen-dependent
      breast cancer. Recently, concerns have been raised regarding the role of zeranol
      (Z), a non-steroidal anabolic growth promoter with potent estrogenic activity
      widely used in the U.S.A. beef industry, as a possible contributor to an
      increased incidence of human breast cancer. This study hypothesized that obese
      individuals may be at greater risk of developing zeranol-induced breast cancer.
      MATERIALS AND METHODS: The aromatase mRNA expression level of three cell types
      isolated from adipose tissues were assayed by RT-PCR, and the cell proliferation
      of primary cultured human normal breast pre-adipocytes (HNBPADs) was investigated
      using the CellTiter96(r) non-radioactive method. The effects of Z and gossypol on
      aromatase expression of leptin-pretreated HNBPADs were evaluated by RT-PCR.
      RESULTS: HNBPADs expressed higher aromatase than primary cultured human breast
      epithelial cells and stromal cells. Z enhanced the mitogenic activity of leptin
      and increased aromatase expression in HNBPADs. Moreover, (-)-gossypol
      counteracted Z- and leptin-induced cell proliferation and aromatase expression.
      CONCLUSION: These results suggested that bioactive Z metabolites contained in
      meat produced from Z-implanted beef cattle may increase estrogen biosynthesis in
      obese individuals by increasing aromatase expression and estrogen production,
      which will promote cell sensitivity and increase breast cancer cell growth.

PMID- 21187494
TI  - Investigation of peroxiredoxin IV as a calpain-regulated pathway in cancer.
AB  - Peroxiredoxin IV (Prx IV), a member of the peroxiredoxin family, has been shown
      to be involved in cell protection against radiation. Peroxiredoxins are also
      overexpressed and involved in the progression of several tumours. Calpains have
      been shown to be over-activated in alveolar rhabdomyosarcoma (ARMS). The present
      study focused on the possible cross-regulations between Prx IV and calpains in
      ARMS cells. Prx IV abundance was quantified by Western blot analysis in ARMS
      cells and compared with non-malignant LHCN-M2 cells. Its abundance is quantified
      in ARMS cells treated or untreated with calpain inhibitors moreover its mRNA
      expression is also quantified by real-time RT-PCR in these cells. The study
      showed that Prx IV is overexpressed by five times in ARMS cells when compared to
      non-malignant myoblasts. Moreover, the inhibition of calpains using chemical
      inhibitors led to a decrease in Prx IV abundance (64.32 +/- 8.25 and 76.79 +/-
      4.60 for the precursor and secretable forms, respectively, with calpain inhibitor
      III treatment). It is the first time that a Prx IV calpain-dependent up
      regulation is revealed. In summary, calpains may be implied in the tumour
      phenotype of ARMS cells especially through Prx IV regulation and may, thus,
      represent a potential therapeutic target to stop progression of ARMS tumour.

PMID- 21187495
TI  - Immunogenicity of dendritic cells pulsed with CEA peptide or transfected with CEA
      mRNA for vaccination of colorectal cancer patients.
AB  - BACKGROUND: Dendritic cells (DCs) are the professional antigen-presenting cells
      of the immune system. We have demonstrated that vaccination of autologous ex vivo
      cultured DCs results in the induction of tumor-specific immune responses in
      cancer patients, which correlates with clinical response. Optimization of antigen
      loading is one of the possibilities for further improving the efficacy of DC
      vaccination. Theoretically, transfection of DCs with RNA encoding a tumor
      specific antigen may induce a broader immune response as compared to the most
      widely used technique of peptide pulsing. PATIENTS AND METHODS: In this clinical
      study, RNA transfection was compared with peptide pulsing as an antigen loading
      strategy for DC vaccination. Patients with resectable liver metastases of
      colorectal cancer were vaccinated intravenously and intradermally 3 times weekly
      with either carcinoembryogenic antigen (CEA)-derived HLA-A2 binding peptide
      loaded or CEA mRNA electroporated DCs prior to surgical resection of the
      metastases. All DCs were loaded with keyhole limpet hemocyanin (KLH) as a control
      protein. Evaluation of vaccine-induced immune reactivity consisted of T-cell
      proliferative responses and B-cell antibody responses against KLH in peripheral
      blood. CEA reactivity was determined in T-cell cultures of biopsies of post
      treatment delayed type hypersensitivity skin tests. RESULTS: Sixteen patients
      were included. All patients showed T-cell responses against KLH upon vaccination.
      CEA peptide-specific T-cells were detected in 8 out of 11 patients in the peptide
      group, but in none of the 5 patients in the RNA group. CONCLUSION: In our study,
      DC CEA mRNA transfection was not superior to DC CEA peptide pulsing in the
      induction of a tumor-specific immune response in colorectal cancer patients.

PMID- 21187496
TI  - HPV genotype distribution in oral and oropharyngeal squamous cell carcinoma using
      seven in vitro amplification assays.
AB  - BACKGROUND: Molecular and epidemiologic evidence indicates that human
      papillomavirus (HPV) is involved in the etiology of oral and oropharyngeal
      squamous cell carcinomas (SCCs). HPV(+) tumors appear to be clinically distinct
      from HPV(-) tumors, conferring improved survival outcomes for patients.
      Determination of the HPV status of tumors may assist in patient risk
      stratification and ultimately guide optimum treatment. The primary aim of this
      study was to examine the distribution of HPV in oral and oropharyngeal SCCs as
      assessed using seven different in vitro amplification assays. The secondary aim
      was to correlate the distribution of HPV in tumors with clinical and demographic
      patient data. MATERIALS AND METHODS: Sixty-eight invasive oral/oropharyngeal SCCs
      were tested for HPV using four laboratory-developed PCR assays for HPV16 or 18
      and three commercial tests, INNO-LiPA(r) HPV Genotyping Extra (Innogenetics),
      Linear Array(r) HPV Genotyping Test (Roche Diagnostics), and Invader(r) HPV16/18
      ASRs (Hologic Corp.). RESULTS: Consensus results between tests revealed that
      71.9% of tumors were HPV(+), primarily with HPV16 (63.2%). Other genotypes were
      uncommon and generally occurred coincidently with HPV16. HPV-positivity was
      significantly higher in oropharyngeal tumors (76.9%), particularly of the tonsils
      (91.7%), versus oral cavity tumors (20.0%). HPV(+) tumors occurred in younger
      patients (average 54.4 years versus 61.1 years) and were significantly associated
      with lower histological differentiation (poorly, 100.0%; moderately, 65.6%; well
      differentiated, 42.9%). CONCLUSION: A high rate of HPV-positivity, especially
      involving HPV16, occurred in oropharyngeal tumors, with a lower rate in oral
      cavity SCCs; however, solitary infections with HPV18, 33 or 45 in a minority of
      cases signified the potential oncogenicity of these additional genotypes and the
      likely need to screen for these less common genotypes in clinical specimens.

PMID- 21187497
TI  - Carbon ion radiotherapy for treatment of prostate cancer and subsequent outcomes
      after biochemical failure.
AB  - BACKGROUND/AIM: Carbon ion radiotherapy is expected to be suitable to treat
      localized prostate cancer because it yields great biological and physical
      effects. The aim of this study was to examine long-term results and subsequent
      outcomes after biochemical failure. PATIENTS AND METHODS: A total of 254 patients
      were treated from the beginning of 2003 and followed through 2009. Long-term
      hormone therapy was also used for some intermediate-risk and high-risk patients.
      RESULTS: Among the patients examined, 54 patients experienced biochemical
      failure. Failure-free survival was 76%, 91% and 76% at eight years in low-risk,
      intermediate-risk and high-risk patients, respectively. Clinical progression
      occurred only in high-risk patients, with 89% progression-free survival at eight
      years. After biochemical failure, diseases of most patients were well controlled
      by salvage therapy but twelve high-risk patients (5%) died of prostate cancer.
      CONCLUSION: Carbon ion radiotherapy had an excellent effect on localized prostate
      cancer. Factors influencing salvage therapy included PSA kinetics and duration
      between radiation and failure.

PMID- 21187498
TI  - Oxaliplatin-induced pancreatitis: a case series.
AB  - BACKGROUND: Drug-induced pancreatitis is less common compared to other causes of
      acute pancreatitis; the incidence ranges from between 0.1% to 2% of acute
      pancreatitis cases. Among alkylating agents, oxaliplatin has not been reported to
      be associated with acute pancreatitis. PATIENTS AND METHODS: This case study
      presents a series of six cases of acute pancreatitis presumably related to
      exposure to oxaliplatin which had different gastrointestinal malignancies and
      were being treated with oxaliplatin in combination with other chemotherapeutic
      drugs. All other related causes of acute pancreatitis were excluded before
      implicating oxaliplatin as a possible cause. RESULTS: In all cases, oxaliplatin
      was stopped and patients had resolution of their signs and symptoms, along with a
      decrease in serum amylase and lipase levels. CONCLUSION: Knowledge regarding
      acute pancreatitis related to oxaliplatin is of paramount importance in order to
      diagnose cases early and institute effective treatment in patients who are
      undergoing chemotherapy with this drug.

PMID- 21187499
TI  - A mediastinal somatic-type germ cell tumor with hepatic metastasis successfully
      treated by multiple modalities.
AB  - Rhabdomyosarcoma in the mediastinum coexisting with metastatic non-seminomatous
      germ cell tumor, so-called somatic-type malignancy, is a rare carcinoma and has
      poor survival. This study reports a case of diffuse and huge hepatic metastasis
      of non-seminomatous germ cell tumor associated with coexisting embryonal
      rhabdomyosarcoma in the mediastinum. A 31-year-old man presented with abdominal
      pain and was found to have multiple abnormal hepatic masses on abdominal computed
      tomography (CT). Concomitantly, an anterior mediastinal mass was found on chest
      CT. Chemotherapy was initiated because the hepatic lesion was diagnosed as
      choriocarcinoma, based on histological findings and the elevation of chorionic
      gonadotropin beta-subunit and alpha-fetoprotein. After six cycles of bleomycin,
      etoposide and cisplatin chemotherapy the metastatic liver tumors showed complete
      response. The remaining mediastinal tumor was completely and successfully
      resected. The histological findings revealed mature teratoma with embryonal
      rhabdomyosarcoma. The patient has remained well for over six years after the
      treatment without any signs of disease recurrence.

PMID- 21187500
TI  - Prognostic and predictive implications of EGFR mutations, EGFR copy number and
      KRAS mutations in advanced stage lung adenocarcinoma.
AB  - BACKGROUND/AIM: Gefitinib and erlotinib were shown to be particularly effective
      in a clinically selected subpopulation of non-small cell lung cancer patients
      (NSCLC): adenocarcinoma histology, non-smoking status, Asian origin and female
      gender have been associated with improved clinical benefit compared to the
      unselected NSCLC population. The aim of the present study was to investigate the
      prognostic and predictive role of EGFR and KRAS analysis in advanced lung
      adenocarcinomas, selected according to clinical features associated to better
      response to EGFR tyrosine kinase inhibitors (TKIs), namely female gender and non
      smoker or former light smoker status. PATIENTS AND METHODS: EGFR and KRAS
      mutations and EGFR FISH status were assessed in 67 surgical samples. RESULTS:
      EGFR and KRAS mutations were found in 16 (26.7%) and 12 (17.9%) patients,
      respectively. FISH analysis was positive in 34 (56.7%) patients. EGFR-mutated
      patients showed significantly longer survival when treated with EGFR TKIs (p =
      0.002, hazard ratio (HR) = 0.036, 95% confidence interval (CI): 0.004 -0.303).
      KRAS mutations was found to be an independent negative prognostic factor in
      multivariate analysis (p = 0.008, HR = 3.52, 95% CI: 1.39-8.9). The prognostic
      value of EGFR FISH status was not confirmed in multivariate analysis (p = 0.048,
      HR = 0.47, 95%CI: 0.22-0.99). CONCLUSION: In a group of clinically selected
      patients, EGFR and KRAS analysis was able to define distinct molecular subsets of
      lung adenocarcinoma.

PMID- 21187501
TI  - Glasgow prognostic score is related to blood transfusion requirements and post
      operative complications in hepatic resection for hepatocellular carcinoma.
AB  - BACKGROUND: Systemic inflammation before surgery, as evidenced by the Glasgow
      prognostic score (GPS), predicts postoperative complications and cancer-specific
      survival in various types of cancer. The aim of this study was to evaluate the
      significance GPS in hepatic resection for hepatocellular carcinoma (HCC).
      PATIENTS AND METHODS: Sixty-six patients who underwent elective hepatic
      resections for HCC were include in the study. Patients were classified into three
      groups: GPS 0 [C-reactive protein (CRP)<=1.0 mg/dl and serum albumin >=3.5 g/dl,
      n = 54], GPS 1 [CRP >1.0 mg/dl or serum albumin <3.5 g/dl, n = 11], and GPS 2
      [CRP>1.0 mg/dl and serum albumin <3.5 g/dl, n = 1]. We retrospectively examined
      the association between GPS (0 or 1) and perioperative clinical variables and
      outcome. RESULTS: In univariate analysis, GPS 0 patients had significantly better
      preoperative the retention rate of indocyanine green at 15 minutes (ICGR15)
      (p=0.0418), Child-Pugh classification (p = 0.0075) and model for end-stage liver
      disease score (p = 0.0007) than did GPS 1 patients. In multivariate analysis,
      blood loss and GPS 1 were independent risk factors for pulmonary complications (p
      = 0.0118 for blood loss, p = 0.0143 for GPS 1), red blood cell concentration
      transfusion (p = 0.0036 for blood loss, p = 0.0117 for GPS 1) and flesh frozen
      plasma transfusion (p = 0.0020 for blood loss, p = 0.0044 for GPS 1). Albumin
      product transfusion, duration of operation (p = 0.0478), blood loss (p = 0.0420)
      and GPS 1 (p = 0.0111) were independent risk factors. Disease-free and overall
      survival of GPS 0 and GPS 1 patients were comparable. CONCLUSION: GPS reflects
      preoperative patient status, and is associated with blood transfusion and
      pulmonary complications in elective hepatic resection for HCC.

PMID- 21187502
TI  - Clinical impacts of histological subtyping primary breast cancer.
AB  - BACKGROUND: Treatment decisions in breast cancer depend on TNM classification and
      the assessment of additional variables with have an impact on survival. We
      examined whether histological subtyping breast cancer as either ductal or lobular
      is related to disease outcome. PATIENTS AND METHODS: We examined a large data
      base of 14198 breast cancer patients. RESULTS: Histological sub-classification of
      invasive breast cancer as either ductal or lobular is not correlated with disease
      outcome. However, the data further showed that invasive lobular carcinomas have a
      higher probability of being oestrogen receptor (ER)- and progesterone receptor
      (PR)-positive and a lower probability of being c-erbB2-positive. They also showed
      a higher average age at the time of diagnosis in comparison with invasive ductal
      carcinoma. Local recurrence rates were lower in invasive lobular carcinoma in
      comparison with invasive ductal carcinoma (3.5% vs. 6.2%; p = 0.031). The
      multivariable Cox regression analysis showed that ER, PR, nodal status, grade and
      tumour size predicted disease outcome with statistical significance, while the
      histological subtype (invasive ductal or lobular) was not a significant predictor
      of disease outcome. CONCLUSION: Histological sub-classification of invasive
      breast cancer as either ductal or lobular is not correlated with disease outcome.
      On the other hand our data gives some indication that lobular and ductal breast
      cancer appear to be different biological entities.

PMID- 21187503
TI  - Arabinoxylan rice bran (MGN-3) enhances the effects of interventional therapies
      for the treatment of hepatocellular carcinoma: a three-year randomized clinical
      trial.
AB  - BACKGROUND AND AIMS: This study examined the efficacy of arabinoxylan rice bran
      (MGN-3) in conjunction with an interventional therapy (IT) for the treatment of
      hepatocellular carcinoma patients. PATIENTS AND METHODS: A total of sixty-eight
      patients with hepatocellular carcinoma (stages I and II) participated in the
      study. Patients were randomized to receive IT (30 patients, control group) or
      IT+MGN-3 (38 patients), and randomly divided into two groups using a computer
      generated randomization list. Patients and investigators were blinded. IT
      included transarterial oily chemoembolization (TOCE) or a combination of TOCE and
      percutaneous ethanol injection treatment (PEIT). RESULTS: Patients in the IT+MGN
      3 group showed: (i) lower recurrence of the disease, 31.6% (12/38), as compared
      to 46.7% (14/30) for the control; (ii) higher survival after the second year,
      35%, as compared to 6.7% for the control; (iii) significantly lower alpha
      fetoprotein level, a 38% decrease (p = 0.0001), as compared to baseline value,
      while the control showed no significant change; and (iv) a significant decrease
      in tumor volume, in contrast to the control, which showed no significant change.
      When the results were analyzed according to each IT modality, MGN-3+IT sub-groups
      displayed a greater response to treatment, in every aspect examined, than the IT
      sub-groups alone. However, the patients in the MGN-3+TOCE+PEIT sub-group
      demonstrated greater reduction in AFP levels and longer survival time than the
      MGN-3+TOCE sub-group. CONCLUSION: MGN-3 in conjunction with IT may be useful for
      the treatment of hepatocellular carcinoma and warrants further investigation in
      multiple clinical trials.

PMID- 21187504
TI  - Dopamine excess in patients with head and neck paragangliomas.
AB  - AIM: This study aimed to determine the prevalence of excess dopamine in relation
      to clinical symptoms and nuclear imaging in head and neck paraganglioma (PGL)
      patients. PATIENTS AND METHODS: Thirty-six consecutive patients with head and
      neck PGLs, evaluated between 1993 and 2009, were included. Clinical symptoms,
      dopamine excess (urinary 3-methoxytyramine (3-MT) or dopamine and/or plasma
      dopamine or 3-MT) and (nor)epinephrine excess (urinary (nor)metanephrine) as well
      as (111)In-octreotide and (123)I-metaiodobenzylguanide (MIBG) scintigraphy were
      documented. RESULTS: Dopamine excess was found in seven patients (19.4%), but was
      unrelated to clinical signs and symptoms. Excretion of other catecholamines was
      unremarkable, except in one patient with adrenal pheochromocytoma. (123)I-MIBG
      uptake (present in 36.1% of patients) was associated with dopamine excess (p =
      0.03). CONCLUSION: Dopamine excess is present in a considerable percentage of
      patients with head and neck PGL, and its measurement may be useful in follow-up.
      Measurement of other catecholamines is necessary to rule out co-existent
      pheochromocytoma.

PMID- 21187505
TI  - Complications of image-guided transcatheter hepatic chemoembolization of primary
      and secondary tumours of the liver.
AB  - BACKGROUND: Image-guided transcatheter hepatic chemoembolization (TACE) is
      accepted worldwide as an effective treatment for patients with unresectable
      hepatocellular carcinoma (HCC) and for adequate preservation of liver function.
      Although considered relatively safe, TACE has been associated with several
      complications. The aim of this study was to determine the prevalence of the
      complications associated with TACE therapy and to correlate it with certain risk
      factors, either well-known or not yet evaluated. PATIENTS AND METHODS: A total of
      330 chemoembolization procedures performed in 170 patients (117 males and 53
      females) over a period of 64 months were retrospectively analysed. Among the
      patients, 123 had hepatocellular carcinoma, 10 had intrahepatic
      cholangiocarcinoma and 37 had hepatic metastases. The variables considered were:
      tumour histotype, bilioenteric anastomosis, previous or combined treatment with
      radiofrequency thermal ablation, antibiotic prophylaxis, chemotherapeutic agents,
      use of new drug-eluting microspheres, comorbidities such as diabetes, patient age
      and the presence of vascular anatomical variations. RESULTS: A total of 30
      complications occurred in 27 procedures. The total complication rate per
      procedure was 9.1% and approximately 75% of patients had postembolization
      syndrome. The difference in the prevalence of complications was statistically
      significant in the group of diabetic patients (13.3%) compared to the remaining
      patients (6.3%) (p = 0.002) and in patients with biliary stents (25%) compared to
      those without stents (7.75%) (p = 0.027). CONCLUSION: These data show that
      diabetes mellitus and the presence of bilioenteric anastomosis are risk factors
      for developing complications after TACE. The use of new drug-eluting microspheres
      did not increase the risk of complications.

PMID- 21187506
TI  - Efficacy of sunitinib in patients with renal cell carcinoma with bone metastases.
AB  - Bone is the second most common metastatic site in patients with renal cell
      carcinoma presenting with metastases (mRCC) at diagnosis. Complications of
      metastatic bone disease, including bone pain, fractures, spinal cord compression,
      and hypercalcaemia, are the primary cause of decline in the quality of life of
      patients with mRCC. Currently, treatment for mRCC bone metastases is generally
      palliative. Bisphosphonates are also used; however, the efficacy of
      bisphosphonates in conjunction with targeted agents is currently unknown. As
      growth factors play a critical role in the development of bone metastases, there
      is a biological rationale for the use of targeted agents to treat them. We report
      here the case of two patients with mRCC with surgically unresectable sacral bone
      metastases treated with sunitinib, who are still alive with long-term
      stabilization of metastases of 48 and 31 months. Results suggest targeted agents
      such as sunitinib may be an effective treatment for bone metastases.

PMID- 21187507
TI  - Response and safety of sunitinib in a heavily pre-treated metastatic non-small
      cell lung carcinoma patient.
AB  - BACKGROUND: The activity of sunitinib, a multitargeted tyrosine kinase inhibitor
      with antiangiogenic and antitumor activities, has been explored in several solid
      malignancies such as breast, lung, prostate and pancreatic cancer. Currently it
      is approved for the treatment of metastatic renal cell carcinoma and
      gastrointestinal stromal tumors. Non-small cell lung cancer usually presents at
      an advanced or metastatic stage at diagnosis. Treatment options are limited for
      this disease, therefore symptom palliation and patient's quality of life are
      primary objectives of therapy. CASE REPORT: We describe the case of a patient
      (male, 67 years old) with heavily pre-treated metastatic non-small cell lung
      carcinoma who received sunitinib according to the following 3-week schedule: 50
      mg daily for 2 weeks followed by a 1-week rest. The patient completed six months
      of therapy achieving a major disease response without high-grade toxicities.
      CONCLUSION: In this case, sunitinib shows promising single-agent activity in
      pretreated non-small cell lung cancer, with a good toxicity profile and flexible
      administration schedule.

PMID- 21187508
TI  - Nuclear expression of 14-3-3 sigma is related to prognosis in patients with
      esophageal squamous cell carcinoma.
AB  - BACKGROUND: The 14-3-3 sigma gene is transcriptionally activated by p53 after DNA
      damage and facilitates DNA repair during G2 arrest. The present study analyzed
      the clinical significance of 14-3-3 sigma expression in esophageal squamous cell
      carcinoma. PATIENTS AND METHODS: The relationship between 14-3-3 sigma and p53
      expressions was investigated immunohistochemically in surgical specimens of
      primary tumors from 248 patients with esophageal squamous cell carcinoma.
      RESULTS: The positive expression rates of cytoplasmic and nuclear 14-3-3 sigma
      were 61.7% and 41.9%, respectively. There was no correlation between 14-3-3 sigma
      and p53 expression. Positive expression of nuclear 14-3-3 sigma was significantly
      correlated with depth of invasion, stage, lymphatic invasion, and poor prognosis.
      Multivariate analysis indicated that negative expression of nuclear 14-3-3 sigma
      was an independent prognostic factor. CONCLUSION: Evaluation of the expression of
      nuclear 14-3-3 sigma proteins may be useful in predicting the outcome in patients
      with esophageal squamous cell carcinoma.

PMID- 21187509
TI  - Combined chemoradiotherapy for early glottic cancer in clinical practice in
      Japan: analysis of 10 institutions.
AB  - AIM: To conduct a retrospective analysis regarding treatment strategies for early
      glottic cancer (GC) at ten institutions. PATIENTS AND METHODS: A questionnaire
      based survey was used to obtain personal and medical information on patients who
      started radiation therapy for T1 or T2 GC between January 2000 and December 2005.
      RESULTS: A total of 279 patients were registered for the survey, of whom 124
      patients were classified as T1a, with 65 patients as T1b and 87 patients as T2.
      The rates of chemoradiotherapy for T1a, T1b and T2 were 24%, 23% and 60%,
      respectively. A comparison of results for academic and non-academic hospitals
      showed statistically different rates of combination therapy for T1a (6.9% vs.
      39.3%, respectively; p<0.001) and T1b (11.4% vs. 36.6%, respectively; p<0.05) but
      not for T2 (70.0% vs. 54.4%, respectively; p = 0.158). CONCLUSION: In clinical
      practice, combined chemoradiotherapy was performed for early GC at most
      institutions in Tokai District, Japan.

PMID- 21187510
TI  - Pemetrexed-induced eyelid edema: incidence and clinical manifestations.
AB  - BACKGROUND: Pemetrexed-induced eyelid edema is a rare side-effect of pemetrexed
      treatment. PATIENTS AND METHODS: Retrospective analysis of the incidence and
      severity of eyelid edema was conducted in patients treated with pemetrexed in a
      single institution. RESULTS: Eighty-six patients received pemetrexed-containing
      chemotherapy either as a single agent (45 patients) or in combination with cis-
      or carboplatin (41 patients). Two patients (2.3%) with stage IV non-small cell
      lung cancer (NSCLC) presented the edema typically localized in the lower eyelid
      after first-line treatment with carboplatin-pemetrexed. The edema remained
      identical in both patients during treatment and regressed in one patient in whom
      treatment was withdrawn. No other localizations of edema were observed in these
      patients. CONCLUSION: Pemetrexed-induced eyelid edema may be more frequent than
      originally reported. The physiopathological mechanism and, as a consequence, the
      treatment and/or prevention of this apparently benign side-effect remains
      unknown.

PMID- 21187511
TI  - Association between breast cancer risk and the wild-type allele of human ABC
      transporter ABCC11.
AB  - BACKGROUND: International mortality and frequency rates for breast cancer have
      been associated with the wet type of human earwax. It was recently found that
      earwax type is determined by a single nucleotide polymorphism (SNP), 538G>A
      (Gly180Arg), in ABCC11. The G allele determines the wet type of earwax as a
      Mendelian trait with a dominant phenotype. The present study examined the
      association between the frequency rate of breast cancer and the frequency of the
      G allele of ABCC11. PATIENTS AND METHODS: Using blood samples from patients with
      invasive breast cancer (n = 270) and control volunteers (n = 273), the 538G>A SNP
      in ABCC11 was genotyped using the SmartAmp method. RESULTS: The frequency of the
      G allele in breast cancer patients was higher than that in healthy controls. The
      odds ratio for the genotypes (G/G+G/A) to develop breast cancer was estimated to
      be 1.63 (p-value = 0.026), suggesting that the G allele in ABCC11 is associated
      with breast cancer risk. CONCLUSION: This study showed that Japanese women with
      wet earwax have a higher relative risk of developing breast cancer than those
      with dry earwax. The ABCC11 SNPs that determine these phenotypes should be
      further investigated in order to obtain insights into the mechanisms by which
      breast cancer develops and progresses.

PMID- 21187512
TI  - CA19.9 and CEA in transitional cell carcinoma of the bladder: serological and
      immunohistochemical findings.
AB  - BACKGROUND: Reliable blood and urine markers for transitional cell carcinoma of
      the bladder (TCC) do not currently exist. The aim of this prospective study was
      the serological and immunohistochemical evaluation of CA19.9 and CEA in TCC and
      to assess the correlation with different TCC stages. PATIENTS AND METHODS: CA19.9
      and CEA levels were prospectively determined in samples from 231 patients with
      TCC suspected bladder lesions, before transurethral tumor resection.
      Additionally, these serum parameters were determined in 11 patients with initial
      metastatic TCC. Immunohistochemical analysis on CA19.9 and CEA was performed in
      83 patients. RESULTS: Neither CA19.9 nor CEA levels were significantly elevated
      in TCC patients. Patients with muscle-invasive TCC showed significantly higher
      levels of CEA (p = 0.008) and CA19.9 (p<0.001) compared to those with superficial
      TCC. Significantly higher levels were also evident with increasing grade of
      malignancy. Metastatic TCC showed significantly elevated CA19.9 levels compared
      to muscle invasive TCC as well as locally advanced (pT3/pT4/pN+) compared to
      localized TCC (pT2/pN0). Immunohistochemical staining revealed a strong
      correlation between CA19.9 serum levels and staining intensity. CONCLUSION: CEA
      and CA19.9 are not useful markers in primary diagnosis of TCC. However, in
      instances of elevated CEA and CA19.9 levels where gastrointestinal malignancy has
      been excluded, evidence of TCC should be sought. If elevated CEA and CA19.9 are
      present in TCC, serum levels correlate with tumor invasion and grade of
      malignancy.

PMID- 21187513
TI  - Ethinylestradiol improves prostate-specific antigen levels in pretreated
      castration-resistant prostate cancer patients.
AB  - BACKGROUND: Ethinylestradiol was used as palliative treatment for patients with
      advanced prostate cancer (PCa). However, its use has declined after the
      development of combined androgen blockade. In the present study, we analyzed the
      effects of ethinylestradiol on pretreated castration-resistant PCa patients.
      PATIENTS AND METHODS: Twenty-four Japanese patients were orally administered
      ethinylestradiol at a dose of 1.5 mg/day and prostate-specific antigen (PSA) was
      examined. We retrospectively analyzed the proportion of patients achieving a
      decline in PSA of >50% and progression-free and overall survival rates. RESULTS:
      All patients had already been treated with combined androgen blockade followed by
      one or more salvage therapies. Median follow-up time was 227 (range: 42-1490)
      days and median ethinylestradiol treatment time was 195 (range: 3-791) days. The
      proportion of patients achieving a decline in PSA >50% was 70%. Median
      progression-free survival was estimated as 300 days. At the end of the follow-up
      period, one patient had died from PCa. Adverse events occurred in three patients,
      namely elevation of liver enzymes, anorexia, and heart failure in one patient
      each. CONCLUSION: Oral ethinylestradiol administration may be useful for
      treatment of advanced castration-resistant PCa after salvage therapy with a high
      PSA response rate and low adverse event rate.

PMID- 21187514
TI  - A rapid and simple HPLC assay for quantification of capecitabine for drug
      monitoring purposes.
AB  - AIM: Capecitabine, a 5-fluorouracil prodrug, has been integrated into the
      management of multiple cancer types. In order to obtain information about plasma
      levels of capecitabine in patients who had drug intake at home during
      chemotherapy, a simple HPLC method for capecitabine monitoring has been developed
      and validated. PATIENTS AND METHODS: Capecitabine levels were quantified by a
      simple reversed-phase HPLC system with an external standard method. Plasma
      samples were obtained from 12 colorectal cancer patients who underwent
      chemotherapy with capecitabine alone (1000 mg/m(2)) or combined with oxaliplatin
      (130 mg/m(2)). RESULTS: Although there was evidence that capecitabine had not
      been taken according to the chemotherapeutic schedule in two cases, the study
      demonstrated that its combination with oxaliplatin showed no significant drug
      drug interactions. CONCLUSION: Due to its robustness, specificity and
      sensitivity, the method is also well-suited for capecitabine analysis in other
      pharmacokinetic studies.

PMID- 21187515
TI  - Bevacizumab and glioblastomas, a single-centre experience: how disease history
      and characteristics may affect clinical outcome.
AB  - BACKGROUND: In 2009, bevacizumab, a monoclonal antibody to vascular endothelial
      growth factor, received accelerated approval by the United States Food and Drug
      Administration for the treatment of glioblastoma, based on its high response rate
      (RR) and 6-month progression-free survival (PFS-6). However, time to progression
      and overall survival (OS) were disappointing. Since 2008 have been data collected
      evaluating the safety and efficacy of bevacizumab in patients with relapsed
      malignant gliomas. PATIENTS AND METHODS: This is a retrospective review of adult
      patients with recurrent malignant gliomas treated with bevacizumab at a dose of
      10 mg/kg every 14 days; some patients were also treated with irinotecan at a dose
      of 125 mg/m(2) every 14 days. Patients were evaluated for side-effects and
      clinical outcomes of response, progression and survival. RESULTS: Ten patients
      received bevacizumab and nine patients received the combination with irinotecan.
      Both single-agent bevacizumab and combination treatment were well-tolerated. RR
      was of 28% with no complete responses, PFS-6 was 20% and OS was 4.5 months (95%
      confidence interval: 3.07-5.98 months). CONCLUSION: Although well-tolerated, the
      efficacy of bevacizumab was somewhat disappointing, possibly due to the high rate
      of secondary high-grade gliomas in the studied patient cohort and the late use of
      bevacizumab in the course of the disease.

PMID- 21187516
TI  - Association between ataxia telangiectasia mutated gene polymorphisms and breast
      cancer in Taiwanese females.
AB  - AIM: Several epidemiological studies have investigated the association between
      ataxia telangiectasia mutated (ATM) gene polymorphisms and breast cancer risk.
      However, published data are still inconclusive and there are no such studies for
      Taiwan. Thus, the polymorphic variants of ATM were investigated for their
      association with breast cancer in Taiwan for the first time here. PATIENTS AND
      METHODS: In this hospital-based matched case-control study, associations of seven
      ATM single nucleotide polymorphisms (rs600931, rs652311, rs227060, rs227292,
      rs624366 and rs189037) with breast cancer risk in a Taiwanese population were
      investigated. One thousand two hundred and thirty-two patients with breast cancer
      and the same number of age-matched healthy controls recruited were genotyped and
      analyzed. RESULTS: There was a slight difference between breast cancer and
      control groups in the distributions of their genotypic (p = 0.0774) and allelic
      frequencies (p = 0.0217) in the rs189037 polymorphism. As for the other six
      polymorphisms there was no differential distribution. CONCLUSION: Our data
      indicate that ATM polymorphism is associated with breast cancer, and the A allele
      of ATM rs189037 is a minor risky biomarker of breast cancer in Taiwan. The gene
      gene and gene-environment interactions of ATM with other factors is worthy of
      further investigation.

PMID- 21187517
TI  - More than 4 years of progression-free survival in a patient with metastatic renal
      cell carcinoma treated sequentially with sunitinib, everolimus, sorafenib, and
      temsirolimus.
AB  - Until recently, immunotherapy has been the standard of care for patients with
      nonresectable metastatic renal cell carcinoma (mRCC); however, immunotherapy is
      associated with a low response rate and significant toxicity. Because of their
      demonstrated ability to prolong progression-free survival, agents targeting
      vascular endothelial growth factor receptors or the mammalian target of rapamycin
      now have become standard therapies for patients with mRCC. Attaining lasting
      clinical benefits, however, requires multiple lines of therapy. This case study
      reports the case of a 52-year-old man with mRCC who remained free of disease
      progression for 48 months while receiving sequential therapy of sunitinib,
      everolimus, sorafenib, and temsirolimus.

PMID- 21187518
TI  - Age aspects of demography, pathology and survival assessment in colorectal
      cancer.
AB  - AIM: The aim of this study was to assess how age is related to differences in
      stage, tumour differentiation and treatment in colorectal cancer. PATIENTS AND
      METHODS: A retrospective study in a consecutive series of colorectal cancer
      patients (n = 2220) where age was related to demography, stage, tumour
      characteristics, treatment and outcome (OS/CSS) both as a continuous variable and
      grouped by high/low 10th percentiles, as young/old groups, with a third median
      reference group. RESULTS: Young patients had more advanced cancer stages (p =
      0.012), higher N-status (p = 0.011) and more frequent T4/G4 tumours. Old patients
      had higher postoperative mortality and were less likely to receive chemotherapy.
      The proportion of cancer-related deaths was stage-dependent and decreased with
      age. CONCLUSION: Cancer stage, tumour characteristics, treatment and outcome can
      vary with age in colorectal cancer. The increasing proportion of non-cancer
      deaths at a higher age can affect the use of overall survival as an outcome
      parameter, which may be of importance in evaluating clinical and translational
      research.

PMID- 21187519
TI  - Immunohistochemical detection of mutated epidermal growth factor receptors in
      pulmonary adenocarcinoma.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) mutational analysis has
      become essential in determining a therapeutic strategy for lung cancer. This
      study validated the reliability of recently generated rabbit monoclonal
      antibodies that recognise specific mutations of the EGFR protein. PATIENTS AND
      METHODS: Pulmonary adenocarcinoma tissue from 20 previously genotyped specimens
      was prepared for immunohistochemical staining by two antibodies that recognise
      products of in-frame deletions in exon 19 (E746_A750del) and a point mutation
      that replaces leucine with arginine at codon 858 in exon 21 (L858R) of the EGFR
      gene. RESULTS: The findings of EGFR-mutation-specific immunohistochemistry were
      concordant with the results of DNA analysis in 18 of 20 tested samples leading to
      90% sensitivity and 100% specificity of the method. CONCLUSION: This
      immunohistochemical assay for products of representative EGFR gene mutations may
      be performed reliably using tissue specimens from resected pulmonary
      adenocarcinomas.

PMID- 21187520
TI  - Clinical significance of vimentin-positive gastric cancer cells.
AB  - BACKGROUND/AIM: Vimentin expression in epithelial cells is reported to be
      associated with the malignant phenotype of cancer cells in vitro. However, the
      clinical significance of vimentin expression in carcinomas is not well
      understood. The aim of this study was to clarify the significance of vimentin
      positive gastric cancer (GC). PATIENTS AND METHODS: A total of 265 GCs were
      examined by immunofluorescent staining with antibodies against vimentin and
      carcinoembryonic antigen. GCs were determined to be vimentin-positive when cells
      were positive for both vimentin and carcinoembryonic antigen staining. RESULTS: A
      total of 86 (32%) of 265 GCs were vimentin positive. There was a statistically
      significant correlation between vimentin-positive GCs and advanced clinical stage
      (p<0.001), macroscopic scirrhous-type (p < 0.001), histological diffuse-type (p <
      0.001), lymph node metastasis (p = 0.008) and lymphatic invasion (p = 0.013). The
      prognosis of patients with vimentin-positive GCs was significantly (p < 0.001)
      worse than that with vimentin-negative GCs. CONCLUSION: Vimentin expression might
      contribute to the high invasive phenotype of GC, and may be a useful biomarker to
      determine the biological aggressiveness of GC.

PMID- 21187521
TI  - Combination chemotherapy with S-1 and platinum in advanced hepatocellular
      carcinoma.
AB  - BACKGROUND: Based on its potent inhibition of dihydropyrimidine dehydrogenase
      (DPD), S-1 is expected to be more active than other flouropyrimidines against
      tumors with higher DPD activity, such as hepatocellular carcinoma (HCC). PATIENTS
      AND METHODS: We retrospectively investigated the efficacy of S-1 and platinum in
      HCC. Patients received S-1 (80 mg/m(2)/day on days 1-14) with either cisplatin
      (60 mg/m(2) on day 1) or oxaliplatin (130 mg/m(2) on day 1) every 3 weeks. The
      primary end point was overall response rate. RESULTS: Among the 21 HCC patients,
      12 and 9 patients received S-1-based chemotherapy as a first-line and salvage
      treatment, respectively. Partial response was seen in 5 patients and stable
      disease in 6. The median time-to-progression was 4.0 months (95% confidence
      interval [CI], 2.4-5.6) and median overall survival was 14.0 months (95% CI, 6.7
      21.3). Most patients were tolerable to chemotherapy and no grade 4 toxicity was
      observed. Tumors with lower DPD expression were more responsive to the therapy
      (response rate 60.0% in lower vs. 0.0% in higher DPD, p=0.045). CONCLUSION: S-1
      and platinum combination chemotherapy shows favorable efficacy and tolerability
      in advanced HCC.

PMID- 21187522
TI  - KRAS genotyping as biomarker in colorectal cancer: a comparison of three
      commercial kits on histologic material.
AB  - BACKGROUND/AIM: The crucial role of KRAS status in new colorectal cancer target
      therapy raises the issue regarding which testing method to use. This study
      analysed 112 formalin fixed, paraffin-embedded (FFPE) metastatic tissue samples
      using three different commercially available kits. PATIENTS AND METHODS: A group
      of 40 KRAS wild-type (wt), 40 codon 12-mutated and 32 codon-13 mutated samples,
      previously evaluated by real-time PCR (TheraScreen kit), used as reference
      method, were analysed by Ampli-set-K-RAS and K-RAS StripAssay kit (herein called
      kit A and B, respectively) based on two different technologies. RESULTS: The
      sensitivity of both kits was 92.5% for wt samples, 100% and 95.0% for kit A and
      B, respectively for samples mutated in codon 12. The specificity was 100% for
      both kits for all groups of samples. After a minor modification of the kit A
      method, its specificity reached 100%. CONCLUSION: of low cost and easy to use,
      kit A may be suitable for use in a routine diagnostic setting.

PMID- 21187523
TI  - Association between EGF, TGF-{beta}1, TNF-{alpha} gene polymorphisms and cancer
      of the pancreatic head.
AB  - BACKGROUND: To date, EGF 61*A/G, TGF-beta1 -509*T/C and TNF-alpha -308*A/G gene
      polymorphisms have been not been analysed in pancreatic carcinoma. This study
      investigated the frequency of these gene polymorphisms among patients with cancer
      of the pancreatic head. PATIENTS AND METHODS: A total of 73 pancreatic head
      cancer patients and 117 cancer-free healthy people were recruited at the Surgical
      Department of the University Hospital Mannheim. Genomic DNA was isolated from
      peripheral blood and gene polymorphisms were analysed by PCR-RFLP. RESULTS: The
      distribution of EGF 61*G/G homozygotes among pancreatic head cancer patients was
      more frequent than that in the control group (24.7% vs 11.1%, odds ratio (OR) =
      2.618, 95% confidence interval (CI) = 1.195-5.738). In addition, the frequency of
      the G allele in the pancreatic head cancer patient group was also higher than
      that in the control group (45.9% vs. 33.3%, OR = 1.696, 95% CI = 1.110-2.592). No
      difference was found for the TGF-beta1 -509 and TNF-alpha -308 genotypes among
      pancreatic head cancer patients and healthy controls. CONCLUSION: The frequencies
      of the EGF 61*G/G genotype and G allele are significantly increased among
      patients with pancreatic head cancer. TGF-beta1-509*T/C and TNF-alpha -308*A/G
      gene polymorphisms are not related to this cancer entity.

PMID- 21187525
TI  - The effects of two methods of Class III malocclusion treatment on
      temporomandibular disorders.
AB  - The aim of this research was to evaluate, within a controlled clinical study, the
      effects of a Delaire-type facemask or a modified Jasper Jumper (JJ) used in the
      treatment of children with Class III malocclusions due to maxillary retrognathia
      on temporomandibular disorders (TMDs). Forty-six patients with Class III
      malocclusions referred for orthodontic treatment were divided into two groups, a
      test and a control. The test group comprised 33 randomly chosen patients (15
      females, 18 males) aged 8-11 years. The control group included 13 patients (eight
      females, five males) with similar features. TMD assessment was performed before
      and after treatment using a two-axis questionnaire, the Research Diagnostic
      Criteria for Temporomandibular Disorders (RDC/TMDs). Qualitative data were
      evaluated using chi-square and McNemar tests. No statistically significant
      differences related to the presence of TMD were observed pre- or post-treatment
      (P > 0.05). The most commonly encountered diagnosis was arthralgia in the JJ
      group both before and after treatment. Evaluation of joint and muscle regions
      showed decreased symptoms, apart from the diagnosed discomforts, in the JJ group
      (P < 0.05). Reduced symptoms were observed in the Delaire group; however, this
      reduction was not statistically significant. An increase, not considered to be
      statistically significant, was observed in the control group. The Delaire-type
      facemask and modified JJ used in the early phase of Class III malocclusion
      treatment did not result in TMD.

PMID- 21187526
TI  - Resonance frequency analysis of orthodontic miniscrews subjected to light
      emitting diode photobiomodulation therapy.
AB  - The aim of this prospective experimental study was to evaluate the effect of
      light-emitting diode (LED) photobiomodulation therapy (LPT) on the stability of
      immediately loaded miniscrews under different force levels, as assessed by
      resonance frequency analysis (RFA). Sixty titanium orthodontic miniscrews with a
      length of 8 mm and a diameter of 1.4 mm were implanted into cortical bone by
      closed flap technique in each proximal tibia of 15 New Zealand white adult male
      rabbits (n = 30). The animals were randomly divided into irradiated and control
      groups under different force levels (0, 150, and 300 cN). OsseoPulse(r) LED
      device (Biolux Research Ltd.) 618 nm wavelength and 20 mW/cm(2) output power
      irradiation (20 minutes/day) was applied to the miniscrews for 10 days. The RFA
      records were performed at miniscrew insertion session (T1) and 21 days after
      surgery (T2). Wilcoxon and Mann-Whitney U-tests were used for statistical
      evaluation at P < 0.005 level. It was found that initial primer stability of all
      miniscrews was similar in all groups at the start of the experimental procedure.
      Statistically significant differences were found for changes in implant stability
      quotient (ISQ) values between LED-photobiomodulated group and the control (0 cN,
      P = 0.001; 150 cN, P < 0.001; and 300 cN, P < 0.001). Significant increase was
      found in ISQ values of LPT applied miniscrews under 0 cN (+11.63 ISQ), 150 cN
      (+10.50 ISQ), and 300 cN (+7.00 ISQ) force during observation period. By the
      increase of force levels, it was determined that ISQ values decreased in non
      irradiated control miniscrews. Within the limits of this in vivo study, the
      present RFA findings suggest that LPT might have a favourable effect on healing
      and attachment of titanium orthodontic miniscrews.

PMID- 21187527
TI  - Morphometric analysis of treatment effects of bone-anchored maxillary protraction
      in growing Class III patients.
AB  - The aim of the present morphometric investigation was to evaluate the effects of
      bone-anchored maxillary protraction (BAMP) in the treatment of growing patients
      with Class III malocclusion. The shape and size changes in the craniofacial
      configuration of a sample of 26 children with Class III malocclusions
      consecutively treated with the BAMP protocol were compared with a matched sample
      of 15 children with untreated Class III malocclusions. All subjects in the two
      groups were at a prepubertal stage of skeletal development at time of first
      observation. Average duration of treatment was 14 months. Significant treatment
      induced modifications involved both the maxilla and the mandible. The most
      evident deformation consisted of marked forward displacement of the maxillary
      complex with more moderate favourable effects in the mandible. Deformations in
      the vertical dimension were not detected. The significant deformations were
      associated with significant differences in size in the group treated with the
      BAMP protocol.

PMID- 21187528
TI  - Ultrastructure and morphology of biofilms on thermoplastic orthodontic appliances
      in 'fast' and 'slow' plaque formers.
AB  - The aim of this study was to investigate the morphological features and
      distribution of biofilms on Invisalign orthodontic appliances, in a sample of
      'slow' and 'fast' plaque formers using scanning electron microscopy (SEM). Fifty
      six Chinese male/female volunteers (aged 19-39 years) were screened for their
      plaque-forming rate using the plaque percentage index (PPI) coupled with digital
      photography and computer-based image analysis, after a period of 48 hours of
      abstinence from oral hygiene procedures. Eleven volunteers (seven males/four
      females) representing the lowest and highest ends of the plaque formation
      spectrum were chosen as slow and fast plaque formers, respectively. The subjects
      wore a full-coverage splint appliance, in which four tiles of Invisalign material
      were embedded. These tiles were collected at intervals of 1, 3, 6, 12, 24, and 48
      hours, as well as 3, 7, and 14 days, immediately fixed in 10 per cent
      paraformaldehyde in 0.2 M cacodylate buffer solution and prepared for SEM. The
      surface configuration of the Invisalign appliance was visualized, as well as the
      chronological pattern of biofilm formation. Significance between fast and slow
      plaque formers was determined using a Student's t-test. Colonization appeared to
      centre initially on the raised edges or textured surfaces of the appliance, and
      initial adhesion was quicker and more abundant in the fast plaque-forming group.
      In the later stages of biofilm development, both groups showed no discernible
      differences in biofilm accrual on the surfaces, but the fast group displayed a
      more complex biofilm structure. More recessed and sheltered areas of the
      appliance, such as the cusp tips and attachment dimples, harboured more biofilm
      than the flat surfaces. Hence, it seems that the novel Invisialign orthodontic
      appliance is a useful tool to investigate the features of biofilm formation in
      time-course studies.

PMID- 21187529
TI  - Differential expression of myosin heavy chain isoforms in the masticatory muscles
      of dystrophin-deficient mice.
AB  - The dystrophin-deficient mouse (mdx) is a homologue animal model of Duchenne
      muscular dystrophy (DMD) and is characterized by slowly progressive muscle
      weakness accompanied by changes in myosin heavy chain (MyHC) composition. It is
      likely that the masticatory muscles undergo similar changes. The aim of this
      study was to examine the masticatory muscles (masseter, temporal, tongue, and
      soleus) of 100-day-old mdx and control mice (n = 8-10), and the fibre type
      distribution (by immunohistochemistry) as well as the expression of the
      corresponding MyHC messenger RNA (mRNA) (protein and mRNA expression, using
      Western blot or quantitative real-time polymerase chain reaction (RT-PCR)).
      Immunohistochemistry and western blot analysis revealed that the masticatory
      muscles in the control and mdx mice consisted mainly of type 2 fibres, whereas
      soleus muscle consisted of both type 1 and 2 fibres. In the masseter muscle, the
      mRNA in mdx mice was not different from that found in the controls. However, the
      mRNA content of the MyHC-2b isoform in mdx mice was lower in comparison with the
      controls in the temporal muscle [11.9 versus 36.9 per cent; P < 0.01; mean +/-
      standard error of the mean (SEM), Student's unpaired t-test], as well as in the
      tongue muscle (65.7 versus 73.8 per cent; P < 0.05). Similarly, the content of
      MyHC-2x isoforms in mdx tongue muscle was lower than in the controls (25.9 versus
      30.8 per cent; P < 0.05). The observed down-regulation of the MyHC-2x and MyHC-2b
      mRNA in the masticatory muscles of mdx mice may lead to changed fibre type
      composition. The different MyHC gene expression in mdx mice masticatory muscles
      may be seen as an adaptive mechanism to muscular dystrophy.

PMID- 21187530
TI  - Radiographic position of the hyoid bone in children with atypical deglutition.
AB  - The persistence of childlike deglutition after the replacement of deciduous teeth
      is described as atypical deglutition. This condition has been attributed to
      sucking action without nutritive purposes, use of a feeding bottle, oral
      respiration, and anatomical abnormalities. Among the possible anatomical
      alterations, the hyoid bone, as a result of being the origin or the insertion of
      several muscles involved in swallowing, may have its position altered in cases of
      atypical deglutition. The aim of the present study was to evaluate the position
      of the hyoid bone using lateral teleradiographs, among patients with atypical
      deglutition during the stage of mixed dentition. Using cephalometric analysis on
      lateral teleradiographs, the distances of H-MP (hyoid to mandibular plane) and H
      T (hyoid to tuber) were measured in two groups: the experimental group with
      atypical deglutition and the control group normal deglutition. Both groups
      included subjects in mixed dentition stage. Measurements from the groups were
      compared using Mann-Whitney U-test and a P-value <0.05 was considered as an
      indication of statistical significance. The average distance of the H-MP variable
      was 11.69 mm for the control group and 16.14 mm for the experimental group, with
      a statistically significant difference (P = 0.016). The average distance of the H
      T variable was 2.26 mm for the control group and -5.89 mm for the experimental
      group, with significant difference (P < 0.001). There was no correlation among
      the variables studied. Cephalometric analysis of the H-MP distance revealed a
      mean difference of approximately 5 mm between the two groups, and the difference
      was more than 7 mm for H-T distance. Distances of H-MP and H-T based on
      radiographic measurements were greater in individuals with atypical deglutition
      than in control group and there was no correlation between these two parameters.

PMID- 21187531
TI  - Mandibular third molar space in different antero-posterior skeletal patterns.
AB  - Retromolar space has long been identified as a major factor in the aetiology of
      mandibular third molar impaction. The aims of this study were to compare
      mandibular third molar space between the different antero-posterior (A-P)
      skeletal patterns, between erupted and impacted third molars in the different A-P
      skeletal patterns, and to report on the status of third molar eruption/impaction
      among the studied subjects. A total of 432 mandibular third molars in 270
      subjects (132 females and 138 males) were investigated from dental pantomograms
      (DPTs) and lateral cephalograms (LC). The average age for the total sample was
      20.80 +/- 2.03 years. The subjects were divided into three groups according to
      their ANB angle as follows: skeletal Class I (144 third molars in 90 subjects),
      skeletal Class II (145 third molars in 95 subjects), and skeletal Class III (143
      third molars in 85 subjects). Each group was subdivided into impacted and erupted
      subgroups. DPT and LC were traced and the following variables were measured:
      retromolar space width, third molar width and angulation, beta angle, second
      molar angulation, mandibular length, and gonial angle. Independent t-test,
      analysis of variance, and chi-square test were used for statistical analysis.
      Retromolar space width in the Class III subjects was smaller than in the Class I
      subjects (P < 0.05). Mandibular third molars were recorded as impacted in 26, 32,
      and 42 per cent of the Class I, II, and III subjects, respectively (P < 0.001).
      The impacted groups had a reduced retromolar space width, increased beta angle,
      and reduced third molar angulation in all A-P skeletal patterns. Class III
      subjects showed increased mandibular third molar impaction with reduced
      retromolar space width.

PMID- 21187532
TI  - Mortality after hip fracture in Japan: the role of nutritional status.
AB  - PURPOSE: To assess factors that influence 4-year mortality following hip fracture
      surgery in a Japanese population. METHODS: Records of 129 hips in 24 men and 103
      women aged 50 to 103 (mean, 79) years who underwent surgery for femoral neck or
      trochanteric fractures were reviewed. Clinical data reviewed included age,
      gender, body mass index (BMI), side of fracture, fracture type, fracture
      stability, surgery type, interval from admission to surgery, length of hospital
      stay, number of pre-fracture comorbidities, pre-fracture ambulatory level, pre
      fracture place of residence, preoperative dementia, preoperative skeletal
      traction, blood haemoglobin level, serum albumin level, number of postoperative
      complications, and postoperative delirium. Univariate and multiple logistic
      regression analyses were performed to identify the relative contribution of the
      variables to mortality. Receiver operating characteristic (ROC) curves were used
      to identify optimal cut-off levels. RESULTS: The 4-year mortality was 48%.
      Multiple logistic regression analysis showed that serum albumin level (p =
      0.0004, odds ratio [OR] = 5.8541) and BMI (p = 0.0192, OR = 1.1693) significantly
      influenced mortality; the cut-off points were 36 g/l and 18.9 kg/m square,
      respectively, based on the ROC curves. Kaplan-Meier curves showed that survival
      rates were significantly worse in patients with values below these cut-off
      points. CONCLUSION: Serum albumin level and BMI on admission are predictive of
      mortality after hip fracture surgery.

PMID- 21187533
TI  - Risk factors leading to total hip arthroplasty in patients with subchondral
      insufficiency fractures of the femoral head.
AB  - PURPOSE: To retrospectively evaluate factors leading to total hip arthroplasty
      (THA) in patients with subchondral insufficiency fractures (SIF) of the femoral
      head. METHODS. 5 men and 22 women aged 51 to 85 (mean, 72) years with SIF of the
      femoral head initially underwent conservative treatment. THA was later performed
      for 13 patients, as the hip pain became worse secondary to joint space narrowing
      and/ or femoral head collapse. Patient demographics and radiological variables
      were retrieved. Risk factors leading to THA in patients with SIF of the femoral
      head were identified. Receiver operating characteristic curves were used to
      determine optimal cut-off values for the significant risk factors. RESULTS: 2 men
      and 11 women aged 62 to 85 (mean, 74.9) years underwent THA and were followed up
      for 0.2 to 62 (mean, 13) months. The remaining 3 men and 11 women aged 51 to 81
      (mean, 68) years underwent conservative treatment and were followed up for 9 to
      93 (mean, 28) months. Patient age was the only risk factor for THA (p = 0.047,
      odds ratio = 1.13), the cutoff value being 71 years (sensitivity, 77%;
      specificity, 64%). The survival rate was significantly lower in patients aged 71
      years or older than in those aged younger than 71 years (p < 0.05). CONCLUSION:
      Elderly patients with SIF of the femoral head are at higher risk of undergoing
      THA.

PMID- 21187534
TI  - The ten-year pattern of hip diseases in Singapore.
AB  - PURPOSE: To review patients with hip diseases undergoing total hip arthroplasty
      (THA) during 2 different periods. METHODS: During the periods 1994 to 1996 and
      2004 to 2006, 12 men and 28 women (mean age, 57 years) and 55 men and 78 women
      (mean age, 62 years) underwent THA for hip diseases, respectively. The
      aetiologies of the hip diseases were classified. Preand post-operative
      radiographs of the pelvis and hip were reviewed. The femoral head-tilt ratio
      (FHR) was measured. RESULTS: The number of patients undergoing THA increased 3
      fold over 10 years; the proportion of different aetiologies was similar.
      Respectively, the most common aetiologies were acetabular dysplasia (33% vs. 40%)
      and avascular necrosis (33% vs. 42%). Only less than 5% of the patients had
      advanced osteoarthritis with no demonstrable cause, most of whom being
      Caucasians. The overall mean FHR was 1.07. There was no significant difference
      between male and female subjects. CONCLUSION: The pattern of hip diseases in
      Singapore remained similar over the 10-year interval, but the number of patients
      undergoing THA had increased 3-fold.

PMID- 21187535
TI  - Morphology of the proximal femur in a Pakistani population.
AB  - PURPOSE: To measure the morphology of the proximal femur in a Pakistani
      population. METHODS: Standardised anteroposterior pelvic radiographs of 116 male
      and 20 female healthy volunteers aged 20 to 50 (mean, 33) years were taken.
      Morphologic dimensions of the proximal femur were measured, including canal flare
      index (CFI), morphological cortical index (MCI), femoral head offset, femoral
      head diameter, and femoral head position. RESULTS: Based on the CFI, 67% of the
      subjects had normal canal shapes (CFI, 3.0-4.7), whereas 1% and 33% of the
      subjects had stovepipe shapes (CFI, <3) and champagne-flute shapes (CFI, 4.7
      6.5), respectively. Based on the MCI, 29% of the subjects had cylindrical shapes
      (MCI, <2.7) and 71% had trumpet shapes (MCI, >2.7). CONCLUSION: Morphology of the
      proximal femur in our study population differed significantly from those in
      western populations, indicating regional variation. It could also be due to the
      younger age of our population.

PMID- 21187536
TI  - Effects of tranexamic acid on blood loss during total hip arthroplasty.
AB  - PURPOSE: To assess the effects of tranexamic acid (TA) in patients undergoing
      total hip arthroplasty (THA) for osteoarthritis. METHODS: 42 patients underwent
      primary THA for osteoarthritis by a single surgeon. 10 men and 11 women who did
      not receive TA were controls, whereas 9 men and 12 women who received TA
      constituted the treatment group. Both groups were matched for age, gender, body
      mass index, and American Society of Anesthesiologists grading. The type of
      prosthesis used (cemented or uncemented) was based on the surgeon's preference
      and patient age, activity level and demands. No hybrid prosthesis was used. 10
      minutes prior to incision, a single dose of intravenous TA (10 mg per kg body
      weight) was given to patients in the treatment group. Comparison was made between
      both groups with regard to intra-operative blood loss, postoperative reduction in
      haemoglobin and haematocrit levels, blood transfusion, incidence of deep vein
      thrombosis, and the length of hospital stay. RESULTS: The mean intra-operative
      blood loss (489 [SD, 281] vs. 339 [SD, 184] ml, p = 0.048) and the decrease in
      haemoglobin level (38 [SD, 12] vs. 29 [SD, 10] g/l, p=0.014) were significantly
      higher in the control than the treatment group. Two patients among the controls
      received a transfusion, compared to none in the TA group (p = 0.49, Fisher's
      exact test). The 2 patients who needed blood transfusion had blood losses of 600
      and 690 ml, compared to a mean of 489 ml in the whole group. No patient in either
      group developed deep vein thrombosis or pulmonary embolism up to 3 months.
      CONCLUSION: A single dose of intravenous TA (10 mg per kg body weight) given 10
      minutes prior to THA is a cost-effective and safe means of minimising blood loss
      and reduction in haemoglobin concentrations as well as the need for allogenic
      blood transfusion, without increasing the risk of thromboembolic events.

PMID- 21187537
TI  - Mechanical thromboprophylaxis for patients undergoing hip fracture surgery.
AB  - PURPOSE: To evaluate the rates of deep vein thrombosis (DVT) and pulmonary
      embolism (PE) in hip fracture patients receiving mechanical thromboprophylaxis.
      METHODS: 123 men and 311 women (mean age, 76 years) admitted to our institution
      with hip fractures were included. 95% of patient received mechanical prophylaxis
      using pneumatic calf pumps intermittently for 20 hours or less per day before and
      after surgery. At the surgeon's discretion, 161 (37%) of them received
      concomitant chemical prophylaxis in the form of subcutaneous low-molecular-weight
      heparin (enoxaparin). Signs and symptoms of DVT and PE were monitored daily, as
      were calf and thigh circumference. Diagnoses were confirmed by duplex
      ultrasonography of the lower limbs and/or spiral computed tomography scan of the
      thorax. RESULTS: 13 patients developed symptomatic venous thromboembolism (VTE);
      11 were DVT and 2 were PE. Among DVT patients, 2 had proximal and 9 had distal
      DVT. All these patients underwent anticoagulation and were discharged without any
      complications. No patients developed complications from pneumatic calf pumps
      (foot drop, skin abrasions or stasis). Eight patients developed bleeding
      tendencies during hospitalisation. No patient developed surgical wound
      infections. 12 patients died during hospitalisation; 8 of them from acute
      myocardial infarction or pneumonia, and none from PE. The median length of
      hospital stay was significantly longer in patients with VTE. CONCLUSION: Routine
      use of mechanical thromboprophylaxis is recommended in patients undergoing hip
      fracture surgery.

PMID- 21187538
TI  - Serum levels of bone turnover markers following total joint arthroplasty.
AB  - PURPOSE: To evaluate changes in serum levels of bone turnover markers during the
      first year following a total hip or knee arthroplasty (THA or TKA, respectively).
      METHODS: 34 women and 13 men (mean age, 68 years) with idiopathic hip or knee
      osteoarthritis underwent elective THA or TKA. The serum levels of (1)
      osteoprotegerin, (2) nuclear factor-kappa B ligand (RANKL), (3) osteocalcin, and
      (4) bone-specific alkaline phosphatase (b-ALP) were determined in each patient on
      preoperative day 1 and postoperative day 3 and 7, and month 2, 4, 6, 8, 10, and
      12. RESULTS: All 4 markers changed significantly over the 12-month period. At
      month 12, values of all markers did not return to their preoperative levels
      uniformly. At month 8, the serum levels of osteoprotegerin, osteocalcin, and b
      ALP remained higher than their respective preoperative values. The serum levels
      of RANKL gradually decreased after month 2, rendering this marker a potential
      index for fixation. CONCLUSIONS: Bone turnover markers change following
      arthroplasties. Postoperative month 8 seems to be a milestone in the normal
      course of these markers.

PMID- 21187539
TI  - Medium-term outcome of total hip replacement for dysplastic hips in Singapore.
AB  - PURPOSE: To review medium-term outcomes of 46 patients who underwent total hip
      replacement (THR) for osteoarthritis secondary to dysplastic hips. METHODS:
      Records of 58 hips in 6 men and 40 women aged 32 to 76 (mean, 62) years who
      underwent THR for osteoarthritis secondary to dysplastic hips and had been
      followed up for a mean of 4 (range, 2-8) years were retrospectively reviewed. The
      hips were classified according to the Crowe's grading, Sharp's acetabular angle,
      and centre-edge angle. The radiological uncoverage of acetabular cup (RUAC) index
      was calculated. The outcomes of THR were evaluated in terms of cup inclination,
      RUAC index, cup migration, lysis or loosening (radiolucency), heterotopic
      ossification, component incorporation and positioning, thigh pain, and
      subsidence. RESULTS: 51 of the hips were Crowe's type I, 6 were type II, and one
      was type IV. The mean acetabular angle was 46.3 degrees and the mean centre-edge
      angle was 15.4 degrees. The mean cup, head, and stem sizes were 50.4 mm, 28.7 mm,
      and 10.9 mm, respectively. The mean RUAC index was 16.9% and the mean cup
      inclination was 40.7 degrees. Radiolucency of 1 mm in the acetabular zone I was
      observed in 16 cases, but only one failed. For cemented and uncemented stems, the
      most common positioning was neutral and valgus, respectively. Five patients had
      complications of greater trochanter fracture, aseptic loosening, split calcar,
      stem loosening, and/or heterotopic ossification. CONCLUSION: Conventional THR can
      achieve good medium-term results in low-grade dysplastic hips.

PMID- 21187540
TI  - Revision total hip arthroplasty with femoral impaction bone grafting.
AB  - PURPOSE: To report the radiological and clinical results of revision total hip
      arthroplasty (THA) with femoral impaction bone grafting (IBG). METHODS: 4 men and
      9 women (15 hips) aged 38 to 84 years underwent revision THA with femoral IBG
      using Elite plus stems for aseptic loosening or infection. RESULTS: The mean
      follow-up duration was 7.7 years. The Harris hip score improved from 61.7 to
      83.7. There was no pain in 11 hips and slight pain in 4. The mean subsidence was
      5.7 mm. The mean change of alignment was 1.2 degrees. There was no radiological
      evidence of stem loosening. One stem was revised due to a peri-prosthetic
      fracture. Cortical healing was noted in 11 hips, and trabecular incorporation in
      10. CONCLUSION: Although intra- and post-operative complications were not
      uncommon, femoral IBG is a safe procedure in carefully selected patients and
      offers good medium-term results.

PMID- 21187541
TI  - Knee joint effusion following ipsilateral hip surgery.
AB  - PURPOSE: To correlate patellar reflex inhibition with sympathetic knee joint
      effusion. METHODS: 65 women and 40 men aged 45 to 75 (mean, 65) years underwent
      hip surgery. The surgery entailed dynamic hip screw fixation using the lateral
      approach with reflection of the vastus lateralis for pertrochantric fractures (n
      = 49), and hip hemiarthroplasty or total hip replacement using the Watson-Jones
      approach (n = 38) or hip hemiarthroplasty using the posterior approach (n = 18)
      for subcapital femoral fractures (n = 28) or osteoarthritis (n = 28). Knee joint
      effusion, patellar reflex, and thigh circumference were assessed in both legs
      before and after surgery (at day 0.5, 2, 7, 14, 30, and 45). Time-sequence plots
      were used for chronological analysis, and correlation between patellar reflex
      inhibition and knee joint effusion was tested. RESULTS: In the time-sequence
      plot, the peak frequency of patellar reflex inhibition (on day 0.5) preceded that
      of the knee joint effusion and the thigh circumference increase (on day 2).
      Patellar reflex inhibition correlated positively with the knee joint effusion (r
      = 0.843, p = 0.035). These 2 factors correlated significantly for all 3 surgical
      approaches (p < 0.0005). All 3 approaches were associated with patellar reflex
      inhibition on day 0.5 (p = 0.033) and knee joint effusion on day 2 (p = 0.051).
      CONCLUSION: Surgical trauma of the thigh may cause patellar reflex inhibition and
      subsequently knee joint effusion.

PMID- 21187542
TI  - The practice of unicompartmental knee arthroplasty in the United Kingdom.
AB  - PURPOSE: To survey the current practice of unicompartmental knee arthroplasty
      (UKA) in the United Kingdom. METHODS: Questionnaires were sent to all 341 local
      members of the British Association for Surgery of the Knee to inquire into their
      practice of UKA, including clinical indications, preoperative investigations,
      surgical approach, preferences in implant design, and the role of UKA in relation
      to high tibial osteotomy. RESULTS: 56% of respondents performed less than 16 UKAs
      per year, whereas 16.5% performed over 30 per year. 89.5% of the respondents used
      anteroposterior radiographs as their main investigation tool. Only 30% and 16.5%
      used posteroanterior 30 degrees flexion and varus/valgus stress radiographs,
      respectively, despite being better investigation tools. 57% considered
      arthroscopy, despite its invasive nature. The main contra-indications to UKA were
      anterior cruciate ligament deficiency with instability (95%), focal grade-III
      osteoarthritis in the contralateral compartment (87%), and osteoporosis with
      rheumatoid arthritis (80.5%), but only 59% of respondents considered an inability
      to passively correct a pre-existing varus or valgus deformity as a contra
      indication. 51.5% of respondents preferred minimally invasive approach, 96%
      preferred cemented fixation, and over two thirds used the mobile bearing design.
      72% of respondents expressed preference for total knee arthroplasty over UKA in
      localised lateral compartment osteoarthritis. CONCLUSION: Modern UKA has gained
      popularity in properly selected patients with localised medial compartment
      osteoarthritis, provided the knee is not anterior cruciate ligament deficient and
      any deformity is passively correctable.

PMID- 21187543
TI  - Changing prophylactic antibiotic protocol for reducing Clostridium difficile
      associated diarrhoeal infections.
AB  - PURPOSE: To determine whether a change in prophylactic antibiotic protocol for
      orthopaedic surgeries may reduce the frequency of Clostridium difficile
      associated diarrhoeal infections. METHODS: Records of 1331 patients who underwent
      trauma or elective surgeries involving implantation of metalwork were reviewed.
      231 trauma and 394 elective patients who received intravenous cefuroxime-based
      antibiotic prophylaxis between August 2006 and January 2007 were compared with
      216 trauma and 490 elective patients who received a single dose of gentamicin and
      flucloxacillin or teicoplanin for antibiotic prophylaxis between August 2007 and
      January 2008. Diarrhoeal faecal specimens of 148 (33%) trauma patients and 106
      (12%) elective patients were examined. The outcome variables were the rates of C
      difficile infection and early deep wound infection. RESULTS: There were 32 cases
      of C difficile-associated diarrhoeal infection and 28 cases of early deep wound
      infection. The frequency of C difficile-associated diarrhoeal infection decreased
      after use of the new antibiotic protocol (from 4 to 1%, p = 0.004), particularly
      in the trauma patients (from 8 to 3%, p = 0.02); in the elective patients the
      difference was not significant (from 1 to 0.5%, p = 0.27). The change of
      antibiotic protocol did not significantly affect the incidence of deep wound
      infections in the trauma (p = 0.46) or elective (p = 0.90) patients. The rate of
      C difficile infection was 8-fold higher in the trauma than elective patients,
      both before and after the change of protocol. CONCLUSION: Changing antibiotic
      protocol is one way of reducing the incidence of C difficile-associated
      diarrhoeal infections in orthopaedic patients, without increasing the rate of
      deep wound infections.

PMID- 21187544
TI  - Intramedullary nailing for displaced proximal humeral fractures.
AB  - PURPOSE: To evaluate outcomes of 28 patients who underwent intramedullary nailing
      for displaced proximal humeral fractures. METHODS: 24 women and 4 men aged 38 to
      87 (mean, 65) years underwent intramedullary nailing for displaced proximal
      humeral fractures. 17 (61%) of them were aged >70 years. Fractures were
      classified into 2-part (n = 8), 3-part (n = 17), and 4-part (n = 3), and
      corresponded to AO 11 A3 (n = 8), B1 (n = 3), B2 (n = 9), and C2 (n = 8) types.
      The Constant and Oxford scores were assessed at the final follow-up. RESULTS: All
      patients had bone union except for one who had tuberosity failure. 23 (82%)
      patients had satisfactory-to-excellent and 5 had poor Constant scores; outcomes
      were worse with more complex fractures. 20 (71%) patients had satisfactory Oxford
      scores. Seven (25%) patients had impingement of a nail tip. Other complications
      included avascular necrosis (n = 1), proximal locking screw back-out (n = 1), and
      screw penetration into the joint (n = 1). CONCLUSION: Intramedullary nailing
      provides a stable fixation with minimal soft tissue dissection for displaced
      proximal humeral fractures. It enables early mobilisation and functional
      recovery.

PMID- 21187545
TI  - Intramedullary nailing for diaphyseal forearm fractures in children after failed
      conservative treatment.
AB  - PURPOSE: To evaluate treatment outcomes after intramedullary nailing using Ender
      nails for diaphyseal forearm fractures. METHODS: 11 male and 9 female patients
      aged 6 to 15 (mean, 12) years underwent intramedullary nailing using Ender nails
      plus cast immobilisation for fractures of both the radius and ulna after
      conservative treatment had failed. RESULTS: After a mean follow-up of 24 (range,
      12-30) months, results were excellent in 14 patients, good in 5, and fair in one.
      None was poor. The mean operating time was 36 minutes. The mean time to bone
      union was 10 (range, 7-12) weeks. The mean time in the cast was 6 (range, 4-11)
      weeks. The mean time to implant removal was 8 (range, 6-10) months. All patients
      regained a full range of elbow movement, except in one who had limited supination
      and pronation (<20 degrees) due to a degree of malrotation. Two patients had pain
      owing to nail protrusion. One patient had a superficial infection. One patient
      had transient neurapraxia. CONCLUSION: Intramedullary nailing using Ender nails
      plus cast immobilisation is effective for diaphyseal forearm fractures in
      children after conservative treatment has failed.

PMID- 21187546
TI  - Arthroscopic repair of rotator cuff tears using absorbable anchors with a single
      row technique.
AB  - PURPOSE: To review outcomes of arthroscopic repair of rotator cuff tears using
      absorbable anchors with a single-row technique. METHODS: 66 patients underwent
      arthroscopic repair for rotator cuff tears using absorbable anchors with a single
      row technique. 51 of them aged 37 to 73 (mean, 57) years had been followed up for
      a mean of 29 (range, 20-37) months. The extent of the tear was classified as
      large, medium or small. Functional outcome was assessed using the Constant score.
      Constant scores and re-tear rates in 3 patient groups (classified by patient age
      and tear size) were compared. RESULTS: Among the 66 patients, there were 24
      large, 29 medium and 13 small cuff tears, and a total of 48, 37, and 18 anchors
      were used, respectively. Among the 51 patients, the median Constant score
      improved significantly after arthroscopy (30 vs. 73, p<0.0001). Six shoulders had
      complete re-tears; their median Constant score was 48 and their adjusted Constant
      score was 65%. Complete re-tears occurred more often in patients aged >60 years
      than in those aged 50 to 59 years and <50 years (4/15 vs. 1/22 vs. 1/14), and
      more often in patients with large tears than in those with medium and small tears
      (4/24 vs. 2/29 vs. 0/13). CONCLUSION: Arthroscopic repair of rotator cuff tears
      using absorbable anchors with a single-row technique is reliable in patients aged
      <60 years with small or medium tears.

PMID- 21187547
TI  - Bicycle-spoke injuries of the foot in children.
AB  - PURPOSE: To evaluate the characteristics of bicyclespoke injuries in a suburban
      Indian population. METHODS: 30 male and 11 female children aged 4 to 12 (mean, 6)
      years with bicycle-spoke injuries were prospectively studied. Data collected
      included patient age, gender, position at the time of injury, site, type, and
      characteristics of the injury. According to the Oestern and Tscherne
      classification, soft-tissue injuries were classified into grades 0 to 3. RESULTS:
      37 patients injured the right foot, and 4 the left foot; 34 by the rear wheel and
      7 by the front wheel. All front-wheel injuries involved the forefoot and midfoot.
      73% of injuries involved the lateral aspect of the ankle. The most common injury
      site was the posterior ankle (n = 30), followed by the medial midfoot (n = 7),
      and the forefoot (n = 3). Partial avulsion of heel flap and an exposed Achilles
      tendon were each noted in 2 patients. 10, 13, 14, and 4 patients sustained soft
      tissue injuries of grades 0, 1, 2, and 3, respectively. Eight patients had
      associated fractures. All fractures healed uneventfully. Marginal necrosis of the
      wound was noted in 5 patients, but none required a skin graft. No patient had
      functional impairment or residual tenderness of the foot. CONCLUSION: Bicycle
      spoke injuries usually affected the ankle region, and the wound was usually
      deeper than it appeared on initial examination. Reassessment of the wound after
      48 hours is recommended. Severity of soft-tissue injury was the determinant of
      overall function; bone fractures by themselves did not alter the duration of
      recovery. To prevent bicyclespoke injuries, spoke guards and foot rests should be
      used, and children being carried on a bicycle should wear proper shoes. Education
      on injury mechanism, severity, and preventive measures is also important.

PMID- 21187548
TI  - Differential distraction for relapsed clubfoot deformity in children.
AB  - PURPOSE: To evaluate the long-term outcome of clubfoot correction following
      differential distraction using the Joshi external stabilisation system (JESS).
      METHODS: 13 male and 9 female patients aged 1.5 to 5 years with 28 idiopathic
      clubfeet underwent differential distraction using JESS for relapsed deformity
      after posteromedial soft-tissue release. They were available for review after a
      mean of 12 years. Deformities of the feet were rigid and graded as Dimeglio type
      III or more. Pain, function, and satisfaction were evaluated using a
      questionnaire. Alignments of the forefoot and hindfoot, subtalar motion, ankle
      range of movement, muscle power, foot size, calf circumference, and limb length
      discrepancy were also evaluated. Each foot was rated using the Ponseti scale.
      RESULTS: In 16 patients with unilateral clubfoot, the abnormal side differed
      significantly from the normal side in terms of foot size, calf circumference,
      ankle motion, and Ponseti score. Most affected feet were smaller. The mean
      Ponseti score for the 28 clubfeet was 80. 20 of the feet had good-to-excellent
      and 5 had fair scores, whereas 3 had poor scores (because of recurrence of
      deformity). Most patients were able to perform activities of daily living without
      any problem. The function of the ankle and subtalar joints was limited. Only 3
      feet achieved ankle dorsiflexion of <10 degrees, 15 were beyond neutral to 10
      degrees, 7 were neutral, and 3 were less than neutral. Most patients developed
      pin site infection, but none necessitated premature removal of the assembly or
      any surgical intervention. CONCLUSION: Differential distraction using JESS
      enabled long-term maintenance of correction and good function, despite hindfoot
      stiffness.

PMID- 21187549
TI  - Percutaneous vertebroplasty for osteoporotic compression fractures using calcium
      phosphate cement.
AB  - PURPOSE: To compare percutaneous transpedicular vertebroplasty using calcium
      phosphate cement (CPC) versus conservative treatment for osteoporotic vertebral
      fractures. METHODS: Eight men and 28 women aged 61 to 99 (mean, 80) years with
      osteoporotic vertebral fractures underwent percutaneous transpedicular
      vertebroplasty using CPC. During the same period, 6 men and 32 women aged 53 to
      93 (mean, 77) years underwent conservative treatment. The indication for
      vertebroplasty was a painful unstable fracture, with mobility of the vertebral
      body shown on flexion and extension lateral radiographs. Fractures without
      mobility despite deformity were treated conservatively. RESULTS: In the
      vertebroplasty group, all patients benefited from reduced back pain immediately
      after surgery, and pain relief was maintained at the latest follow-up. However,
      correction loss continued until one month after the operation. The mean visual
      analogue score for pain decreased significantly from preoperation to one day
      after surgery (9.3 vs. 6.2, p=0.02), and further decreased to 2.8 (p = 0.04) on
      day 3 or 4 when ambulation began, and to 1.5 at the one month follow-up and 1.4
      at the final follow-up (mean, 14 months). The mean duration of analgesic
      treatment was significantly shorter in the vertebroplasty than conservatively
      treated group (10.2 vs. 63.5 days). All patients in the vertebroplasty group
      achieved bone union, with no adjacent vertebral fractures. However, in patients
      having conservative treatment, there were 2 adjacent vertebral fractures and 4
      pseudarthroses, and the collapse continued for several months. CONCLUSION:
      Percutaneous transpedicular vertebroplasty using CPC achieves immediate pain
      relief and reduces the risk of vertebral body collapse and pseudarthrosis among
      elderly patients with osteoporotic vertebral compression fractures.

PMID- 21187550
TI  - Anatomy of L4 to S3 nerve roots.
AB  - PURPOSE: To study the course of L4 to S3 nerve roots and their distance with the
      ala of the sacrum and the sacroiliac joint. METHODS: The embalmed left half
      pelvis of 25 male and 27 female cadavers aged 30 to 91 (mean, 68) years were
      studied. The ventral rami of the L4, L5, S1, S2, and S3 nerve roots were
      dissected along their courses from the corresponding intervertebral foramina to
      the lesser pelvis. The distances between each nerve root and the most anterior
      and inferior parts of the sacroiliac joint were measured in both coronal and
      sagittal planes. RESULTS: There were 3 locations of fusion of L4 and L5 nerve
      roots: above, on, or below the level of the most anterior part of the sacroiliac
      joint. Fusion of S1 and S2 nerve roots at the most inferior part of the
      sacroiliac joint was encountered in 10% of pelvises. Most S1 and S2 nerve roots
      lay medial to the sacroiliac joint and closed to the anterior cortex of the ala
      of the sacrum. CONCLUSION: Sacral nerve roots may fuse at different levels. Most
      L4 to S3 nerve roots lie close to the anterior surface of the sacroiliac joint
      and the ala of the sacrum. To prevent nerve root injury, dissection with a sharp
      instrument should be avoided at such area and 5 to 7 mm medial to the sacroiliac
      joint.

PMID- 21187551
TI  - Corresponding scapular pain with the nerve root involved in cervical
      radiculopathy.
AB  - PURPOSE: To correspond scapular pain with the nerve root involved in cervical
      radiculopathy. METHODS: In the anatomic study, 11 Japanese adult cadavers were
      dissected to examine the numbers and courses of the cutaneous nerves from C3 to
      C8 dorsal rami. In the clinical study, 14 men and 11 women aged 34 to 77 years
      who presented with scapular pain as well as pain, numbness or motor weakness in
      the upper limbs secondary to cervical radiculopathy were assessed. The involved
      nerve roots were identified based on the symptoms and signs in the arm and/ or
      fingers, the radiological diagnosis, and the pain response to cervical nerve root
      blocks. The sites and characteristics of radicular pain were assessed. RESULTS:
      In the anatomic study of 22 cutaneous nerves from medial branches of dorsal rami,
      18 involved the C5 nerve root, 0 the C6 root, one the C7 root, and 8 the C8 root.
      In the clinical study, the radicular pain often occurred in the suprascapular
      region involving the C5 root, in the suprascapular to posterior deltoid region
      involving the C6 root, in the interscapular region involving the C7 root, and in
      the interscapular and scapular regions involving the C8 root. All patients with
      C5 or C8 radiculopathy had both superficial and deep pain, whereas almost all
      patients with C6 or C7 radiculopathy had deep pain only. No patient had
      superficial pain only. CONCLUSION: Cervical radiculopathy can cause scapular
      pain. Pain sites and characteristics are related to the affected nerve root.

PMID- 21187552
TI  - Biopsy of vertebral tumour metastasis for diagnosing unknown primaries.
AB  - PURPOSE: To examine patients with vertebral tumour metastasis using
      transpedicular biopsy for diagnosing unknown primary tumours. METHODS: 13 men and
      8 women aged 41 to 80 (mean, 61) years with vertebral tumour metastasis of
      unknown primary origin underwent transpedicular biopsy of the affected vertebra.
      RESULTS: The origins of the primary tumours were lung cancer (n = 6), prostate
      cancer (n = 5), colorectal cancer (n = 5), kidney cancer (n = 4) and lymphoma (n
      = 1). All the specimens matched pathological characteristics of their
      corresponding primary tumours, except in one patient. This 42-year-old man had
      stage-4 colon cancer, in whom the pathologic findings could not enable
      differentiation between colon and prostate cancer. CONCLUSION: Transpedicular
      biopsy of the vertebra is a cost-effective diagnostic tool for evaluating unknown
      primary tumours.

PMID- 21187553
TI  - Pulmonary cement embolism during cement augmentation of pedicle screw fixation: a
      case report.
AB  - We present a case of pulmonary cement embolism during cement augmentation of
      pedicle screw fixation for severe degenerative scoliosis. During intra-operative
      C-arm fluoroscopy, a radio-opaque substance was incidentally noted to pulsate in
      synchrony with the patient's heartbeat. A diagnosis of pulmonary cement embolism
      was made. The patient was treated with coumarin for 6 months. He made a good
      recovery.

PMID- 21187554
TI  - Spinal nerve root herniation into a pseudomeningocele associated with lumbar
      spondylolysis: a case report.
AB  - A 38-year-old man presented with low back pain and sciatica on the left side.
      Magnetic resonance imaging showed spinal nerve root herniation into a
      pseudomeningocele associated with lumbar spondylolysis. After closure of the
      dural defect, the sciatic pain was relieved and subsequently the patient was able
      to return to work.

PMID- 21187555
TI  - Microsurgical resection of cavernous haemangioma around the thoracic
      neuroforamen: a case report.
AB  - Treatment for haemangioma of the spinal cord often results in extensive bony
      resection that necessitates fusion and/or instrumentation. We report on a 75-year
      old man who presented with neuropathic pain and muscle weakness of both lower
      limbs, secondary to an epidural haemangioma at T11-T12, extending laterally into
      the neuroforamen. The tumour was resected within the neuroforamen after a partial
      laminectomy and limited medial foraminotomy at T11-T12, without disruption of the
      osseous continuity of the pars interarticularis, avoiding spinal stabilisation
      surgery.

PMID- 21187556
TI  - Minimally invasive plate osteosynthesis for osteofibrous dysplasia of the tibia:
      a case report.
AB  - Osteofibrous dysplasia occurs most frequently in the tibia and may result in
      deformity and pathological fracture. We report one such case in a 6-year-old girl
      who underwent minimally invasive plate osteosynthesis using a locking compression
      plate. The varus deformity of the tibia was manually corrected, and the plate was
      inserted without extensive surgical exposure. At 20-week follow-up, the fracture
      had healed completely, and she had returned to normal daily living. At 3-year
      follow-up, radiographs showed no progression of the varus deformity. Minimally
      invasive plate osteosynthesis is useful for treatment of pathological fractures
      caused by osteofibrous dysplasia. It preserves blood flow at the fracture site,
      leading to good bone healing and stability to prevent further deformity and an
      early return to daily activity.

PMID- 21187557
TI  - Arthroscopic resection of a bucket handle tear of the meniscus: a technical note.
AB  - Arthroscopic resection of bucket handle tears of the meniscus is difficult owing
      to the obstructed view of the posterior horn. It often requires an additional
      portal for access or additional tools. We describe a technique involving
      conventional tools including grasper, shaver, and basket forceps. No additional
      portal is required. The basket forceps are used to cut the anterior attachment of
      the tear, and the bucket handle is shaved to a suitable size. The grasper is then
      used to hold the remaining meniscus and move it to the posterior space. The
      posterior corner of the meniscus is then turned over so that its posterior horn
      can be seen and accessible for cutting. This technique is primarily for medial
      meniscectomy. For lateral meniscectomy, the conventional technique may suffice,
      as the lateral compartment can be easily expanded between the femur and tibia.

PMID- 21187558
TI  - Diagnostic gait pattern of a patient with longstanding left femoral nerve palsy:
      a case report.
AB  - The gait pattern of a 35-year-old man with longstanding, left femoral nerve palsy
      was assessed using 3-dimensional kinematic and kinetic analysis. Stability of his
      left knee in stance was achieved by manipulating the external moments of the limb
      so that the ground reaction force passes in front of the knee joint. This
      compensatory mechanism of locking the knee in extension is reliant on the
      posterior capsular structures. The patient was managed conservatively and
      continued to walk without aids.

PMID- 21187559
TI  - Anterior dislocation of Insall Burstein II total knee arthroplasty secondary to
      polyethylene tibial post fracture: a case report.
AB  - Anterior dislocation of a posterior stabilised total knee arthroplasty secondary
      to a polyethylene tibial post fracture is rare. We report one such case in an 89
      year-old Chinese woman who had undergone total knee arthroplasty using the Insall
      Burstein II prosthesis 7 years earlier. The failure was due to sagittal
      malalignment of the components. Owing to more pronounced anterior bowing of the
      distal femoral shaft in southern Chinese, neutral component placement is often
      biased toward hyperextension. When the knee reaches full extension, anterior
      impingement occurs. Surgeons must therefore take extra care in preoperative
      planning and bone cutting in this population.

PMID- 21187560
TI  - Traumatic dislocation of the pisiform: a case report.
AB  - Isolated pisiform dislocation is rare. We present one such case in a 20-year-old
      man occurring after a direct injury to the wrist. After an initial delay in
      diagnosis and unsuccessful closed reduction, he underwent resection of the
      pisiform. At 12-month follow-up, he had full range of movement of the wrist and
      no residual pain.

PMID- 21187561
TI  - Letter to the editor: Concomitant fungal and bacterial atlanto-axial
      osteomyelitis: a case report.

PMID- 21187562
TI  - Letter to the editor: Differences in outcome between Maori and Caucasian patients
      undergoing total joint arthroplasty for osteoarthritis.

PMID- 21187563
TI  - Letter to the editor: Continuous infiltration of local anaesthetic following
      total knee arthroplasty.

PMID- 21187564
TI  - Use of botulinum toxin in the treatment of lower urinary tract disorders. Current
      status.
AB  - The role of botulinum toxin in the treatment of lower urinary tract disorders has
      vastly expanded in the last few years. The indications list growing to include
      conditions ranging from detrusor sphincter dyssynergia, neurogenic and idiopathic
      detrusor overactivity, painful bladder syndrome and lower urinary tract symptoms
      consequent upon bladder outflow obstruction. This treatment is minimally
      invasive, shows a remarkable efficacy and has effects lasting up to one year. We
      review the latest evidence both basic science and clinical to address some of the
      key questions regarding this treatment modality. There is an abundance of
      evidence supporting the efficacy, safety and tolerability of this treatment.
      However, It is clear that much work is still required to understand the
      mechanism(s) of action of the toxin and more robust placebo controlled randomised
      trials need to be undertaken to answer the many remaining questions concerning
      this novel treatment. Nevertheless this treatment modality has remarkable
      efficacy and minimal side effects and thus will be a key future treatment option
      for a wide range of indications.

PMID- 21187565
TI  - [Use of botulinum toxin in the treatment of lower urinary tract disorders.
      Current status. Editorial comment].

PMID- 21187566
TI  - Focal therapy for prostate cancer: a potential strategy to address the problem of
      overtreatment.
AB  - Focal therapy for localized prostate cancer involves destroying the cancer focus
      in order to offer patients the potential of combining cancer control with minimal
      side-effects. Current standard of care involves either active surveillance or
      radical therapy. Neither of these is ideal. Active surveillance carries a risk of
      under- treatment, with psychological morbidity as a result of anxiety and is
      associated with side-effects due to repeated biopsies, although radical therapy
      is the gold standard for curative treatment. With the proportion of unifocal or
      unilateral disease among men with low-risk disease rising, a focal approach could
      avoid both under and over-treatment. With the advent of improved accuracy for
      cancer localization provided by multiparametric MRI and new biopsy strategies
      such as transperineal mapping biopsies, ablative modalities such as cryotherapy,
      high intensity focused ultrasound, photodynamic therapy and radio-interstitial
      tumour ablation make focal treatments a real possibility.

PMID- 21187567
TI  - [Focal therapy for prostate cancer: a potential strategy to address the problem
      of overtreatment. Editorial comment].

PMID- 21187568
TI  - Prostate cancer as incidental finding in transurethral resection.
AB  - Prostate adenocarcinoma is found in surgical samples without prior diagnosis in 4
      to 15% of the patients. In some of them, there is previous suspicion but in
      others this finding is completely incidental. We present 7 cases of prostate
      cancer detected in 100 patients who underwent bipolar transurethral resection
      (TUR) of the prostate due to regular indications. The aim of this paper is to
      describe patient's characteristics, postoperative outcome, analyze TURP as a
      diagnostic tool and evaluate therapeutic options for prostate cancer (PCa).
      METHODS: One hundred patients with bladder outlet obstruction due to benign
      prostatic hyperplasia (BPH) underwent TURP in FUCDIM between June 2007 and August
      2009. In 7 of them, prostate adenocarcinomas were detected. None of the patients
      underwent TURP only because of increased prostate-specific antigen (PSA).
      RESULTS: Mean preoperative PSA was 7.6 ng/ml (r= 0.72 -27 ng/ml), 39% of the
      patients had PSA < 4 ng/ml; 33 (40%) had undergone previous biopsies and 36% of
      them had 2 or more previous biopsies. Prostate cancer detection global rate was
      7%, 3 cases were incidental findings (low PSA and low-risk tumors), 3 patients
      had increased PSA and several previous biopsies with negative results and 1 had
      low PSA and aggressive tumor (Gleason 4+3). CONCLUSIONS: TURP patients with
      prostate cancer are a heterogeneous group. TURP can be both diagnostic and
      therapeutic when facing patients with obstructive symptoms, high PSA and negative
      prostate biopsies. There are several therapeutic alternatives for TURP patients
      with cancer, taking into consideration tumor grade and stage, age, life
      expectancy and will of the patient. Bipolar TUR, in selected patients, allows to
      offer optional active surveillance (in these patients PSADT is very useful) and
      if cancer is not found, it eases the follow up of these patients. Active
      treatment (surgery or radiotherapy) is indicated in T1a patients with life
      expectancy longer than 10 years, and in the majority of T1b patients.

PMID- 21187569
TI  - Flexible ureterorenoscopy (URS): technique and results.
AB  - OBJECTIVES: This paper has two main objectives: First, to expose the URS
      technique used in our Department because there are important differences with
      respect to others centres published, explaining same aspect that can benefit to
      the better development of the technique. Second, we present the results of a
      series of 100 cases. Flexible ureterorenoscopy (Flex URS) has been little used to
      date, mainly because of the technical difficulties created by the deficient
      quality of the instruments used, such as ureteroscopes offering scant visibility,
      poor illumination, a small working channel, deficient quality of the forceps and
      baskets, etc. METHODS: We present our recent series of flexible URS for the
      treatment of renal lithiasis. We performes a retrospective analysis of this
      treatment corresponding to the period between January 2007 and March 2010. In
      this period we have treated 100 patients. The medium size of the stone treated is
      1.5cm (0.5-6cm) and we used ureteroscopic protector sheath in all cases. The
      lithotripter system used in all cases was Ho:YAG Laser with 200 and 365 micras
      fibers RESULTS: The stone-free rate (SFR) in the immediate postoperative period
      was 77% (77/100 patients). Residual stones, defined as stone fragments visualized
      in the operating room via fluoroscopy and directly with the flexible
      ureteroscope. Three months after surgery, the SFR was 92.7% (89/96 patients)
      confirmed by intravenous urography. Regarding complications, we had 5 patients
      with ureteral lesions during protector sheath pass and 9 patients that presented
      at the emergency room with pain secondary to the double J catheter. CONCLUSIONS:
      Flexible URS for of renal lithiasis can be defended in stones measuring up to 2
      cm in diameter, based on our treatment algorithm.

PMID- 21187570
TI  - Rupture of the superficial vein of penis: therapeutic options.
AB  - OBJECTIVE: To report an uncommon clinical case of spontaneous rupture of the
      superficial dorsal vein of penis. METHOD: A 27-year-old male patient attended the
      emergency room following spontaneous occurrence of a large hematoma and deformity
      in the penis. Rupture of cavernous bodies was initially suspected. RESULTS:
      Surgical examination revealed rupture of the superficial dorsal vein of penis,
      which was ligated. The patient was admitted to hospital for 24 hours, and showed
      total cosmetic and functional recovery at 2 weeks. CONCLUSIONS: Rupture of the
      superficial dorsal vein of penis is an uncommon condition considered in
      differential diagnosis of penile hematoma. Doppler ultrasound of the penis may
      allow for its diagnosis and for excluding rupture of corpora cavernosa. Although
      conservative management appears to be of choice, surgical examination, providing
      good cosmetic and functional postoperative results, is indicated when a
      reasonable doubt exists about diagnosis.

PMID- 21187571
TI  - Gross calcification on distal end of ureteral stent.
AB  - OBJECTIVE: The commonest indications for ureteral stent placement are:
      obstructive nephrolithiasis, renoureteral surgery, urologic oncology, endourology
      and extrinsic ureteral compression. METHODS: We report the case of a 77-year-old
      male patient with a DJ ureteral catheter placed for an 8-month period and history
      of nephrolithiasis; the stent showed a 60 mm x 30 mm calcification on its distal
      end. RESULTS: Open cystolithotomy and removal of stent resolved the clinic
      symptomatology. CONCLUSION: A prolonged indwell time of stents, as well as a
      history of nephrolithiasis and urinary infections may on many occasions result in
      calcification and encrustation of ureteral stents, and will lead to the use of
      endourology techniques, extracorporeal lithotripsy or open surgery to resolve
      these conditions.

PMID- 21187572
TI  - Villous adenoma in augmentation colocystoplasty asociated to infiltrating
      urotelial cancer in bladder remanent.
AB  - OBJECTIVE: To report a new case of villous adenoma developed in augmentation
      colocystoplasty. METHODS: Characterization of a new case and review of the
      literature published to date. RESULTS: We report the case of a 66 year-old man
      with a villous adenoma and synchronic infiltrating transitional cell carcinoma of
      the bladder after augmentation colocystoplasty. The latency period until the
      development of villous adenoma after surgery is long. Treatment consisted of
      transurethral resection. CONCLUSIONS: Villous adenoma is a benign neoplasm that
      occurs in the colonic mucosa and shows a high ability to become a malignant
      colonic cancer. Only two cases of villous adenoma in augmentation colocystoplasty
      have been reported. We recommend follow up with periodic cystoscopy because of
      its high malignancy potency.

PMID- 21187573
TI  - Adrenal myelolipoma. Contribution of a case and bibliographic review.
AB  - OBJECTIVE: We report the case of adrenal gland myelolipoma. METHODS/RESULTS: The
      patient was a 29 year old who is diagnosed with an adrenal adenoma during an
      endocrinology review. He underwent laparoscopic adrenalectomy. The pathological
      study confirmed the diagnosis of adrenal myelolipoma. CONCLUSIONS: The
      myelolipoma is a rare tumor composed of hematopoietic elements in different
      maturation stages and without histological changes, combined with mature adipose
      tissue in varying proportions. Most of them are incidental findings during
      radiologic complementary tests. Treatment should be tailored to each particular
      case. Surgery is indicated when the mass exceeds the size 4-6 cm or when it is a
      functioning mass.

PMID- 21187574
TI  - Treatment strategies for prevention of cardioembolic stroke in atrial
      fibrillation.
AB  - Stroke is the third leading cause of mortality and is one of the leading cause of
      disability in the world today. Although underused, anticoagulation with warfarin
      is still the treatment of choice for prevention of stroke in patients with AF,
      though hemorrhage is clearly increased in the anticoagulated patient. The
      substantial difficulties associated with warfarin use give reasons for the
      continuing challenge of decision making about antithrombotic therapy. They have
      led to a search for alternative approaches of stroke prophylaxis resulting in a
      strategy of mechanically sealing the left atrial appendage (LAA) and excluding it
      from the systemic circulation. A couple of years ago a percutaneous transcatheter
      transseptal approach to LAA occlusion has become feasible. Since then, valuable
      technical knowledge and a proof of concept emerged from clinical trials using
      three different systems. However, also the intervention bears a risk. Thus,
      identifying those patients who gain the most from either therapy is crucial
      which, in the first line, means to calculate the risk of stroke or bleeding.
      Unfortunately, patients with some defined comorbidities are at risk of both,
      cerebral embolism or hemorrhage. Whether this target group may benefit from LAA
      occlusion is a matter of this discussion.

PMID- 21187575
TI  - Biorheological changes of dendritic cells at the different differentiation
      stages.
AB  - The differentiation, maturation and functioning of Dendritic cells (DCs) are
      dynamic processes. This study investigated the changes of DCs' migration ability
      and biorheological properties during their differentiation. Transmigration assay
      showed that, DCs' migration rate was improved significantly as they differentiate
      (p < 0.05); NSC (Rac1 blocker) treatment could significantly decrease their
      migration rates (p < 0.05). Confocal images showed that, F-actin uniformly
      distributed in monocytes; with DC's differentiation, F-actin began to remodel and
      gather at the site of dendrites; the images presented surface ruffles and uneven
      sawtooth-like cytoskeletal structures. Fluorescence polarization analysis showed
      that, membrane fluidity was increased significantly with DC's differentiation (p
      < 0.05). CD62L was upregulated significantly (p < 0.05) on the third and ninth
      days. CD2 was upregulated significantly (p < 0.05) until the seventh day. DC's
      electrophoretic mobility was increased continuously, especially increased
      significantly from the third day to the fifth day and the final stage (p < 0.05).
      These results indicate that there are significant changes in the biorheological
      properties of DCs during their differentiation.

PMID- 21187576
TI  - The value of contrast enhanced ultrasound (CEUS) in the characterisation of
      patients with renal masses.
AB  - Renal masses are frequently incidentally found on ultrasound. Contrast enhanced
      computed tomography (CECT) is regarded as the method of choice. Contrast enhanced
      ultrasound (CEUS) has a high impact for characterisation of hepatic lesions. Its
      use in renal masses has been less comprehensively studied. Two hundred and one
      patients referred for surgical treatment of a renal mass, 143 patients fulfilling
      inclusion criteria (histology and reference method). Baseline ultrasound and CEUS
      with BR1, histology obtained by surgery (89%) or biopsy (11%). Eighty-eight
      percent of the patients had renal lesions which were malignant and 12% benign
      lesions. Eighty percent had renal cell carcinoma (RCC). Seven percent of the
      lesions were cystic. Two patients were upgraded by CEUS from CECT Bosniak II into
      CEUS Bosniak III resp. IV. CEUS could predict malignancy with a sensitivity,
      specificity, positive, negative predictive value and accuracy in 97%, 45%, 91%,
      75%, and 90%. The correct staging was diagnosed by CEUS (CECT) in 83% (69%). CEUS
      was superior to CECT in the staging and characterisation of RCC, also in the
      subgroup of patients with cystic lesions. CEUS can replace CECT e.g. in patients
      with allergies or contraindications against CECT. Multicentre studies are
      necessary to confirm the findings.

PMID- 21187577
TI  - Role of genetic polymorphisms in myocardial infarction at young age.
AB  - Acute myocardial infarction (AMI) in young adult presents a typical pattern of
      risk factors, clinical, angiographic and prognostic characteristics. In the last
      years we demonstrated that hemorheological profile is altered in these patients
      in a persistent way and independently of the number of risk factors and of the
      extent of coronary lesions. Thus, the hyperviscosity syndrome following AMI could
      be considered an intrinsic characteristic of these patients. Consequently it is
      possible to hypothesise the presence of a genetic background at the origin of
      this predisposition. If this background is able to influence the risk of ischemic
      heart disease, this should be particularly evident in young subjects. Since
      inflammatory mechanisms play a central role in mediating all phases of
      atherosclerosis, genes encoding for inflammatory or anti-inflammatory molecules
      are candidates for the risk of developing atherosclerosis. As atherosclerosis is
      the first cause of mortality in Western countries and if pro-inflammatory
      genotypes contribute to risk of coronary heart disease, alleles associated to
      disease susceptibility should not be included in the genetic background favouring
      longevity: People genetically predisposed to a weak inflammatory activity have
      fewer chances to develop cardiovascular disease and, therefore, have better
      chance for a long-life. According to this hypothesis, we studied in our
      population of young patients with AMI, the distribution of some polymorphisms
      influencing a inflammation and found an higher prevalence of pro-inflammatory
      polymorphisms (SNP A2080G of pyrin gene, SNP Gly670Arg of PECAM gene, C1019T of
      Cx 37 gene, SNP G1059C of PCR gene) and a lower prevalence of anti-inflammatory
      polymorphisms (Asp299Gly of TLR4 gene, SNP -1082 G/A of IL10 gene, CCR5Delta32).
      Results of these studies show that early myocardial infarction could be
      associated with a genetic predisposition to an intense inflammatory response,
      associated also to an hyperviscosity syndrome.

PMID- 21187578
TI  - Erythrocytapheresis and sublingual micro-vascular flow in severe malaria.
AB  - The authors describe clinical cases of two patients admitted to intensive care
      unit following severe Plasmodium falciparum malaria. Patients' sublingual
      microcirculation was monitored by on-line Sidestream dark-field imaging before
      and after treatment with erythrocytapheresis. Before treatment, microcirculatory
      flow alterations were obvious. Therapy produced a rapid decrease in infected red
      blood cells with a significant improvement in microcirculatory flows, capillary
      perfusion and patients' outcome. The present cases emphasize the relevance of
      microcirculation monitoring in patients with capillary perfusion alterations
      resulting from severe malaria. As far as we know, this is the first observations
      of an improvement of capillary perfusion after erythrocytapheresis.

PMID- 21187579
TI  - Age-related carbonyl stress and erythrocyte membrane protein carbonylation.
AB  - Reactive carbonyl species (RCS) have been widely used as indicators of oxidative
      stress. However, the associations of carbonyl stress with aging process and
      biochemical alteration of erythrocyte are still poorly understood. Fresh blood
      samples in vacutainer tubes containing sodium heparinate were obtained from 874
      volunteers who were divided into young, adult and old groups based on their age.
      Plasma RCS and thiols concentrations between different age groups and erythrocyte
      membrane protein carbonylation in the adult group were detected within 24h of the
      blood sampling. Results showed that the plasma thiols concentration decreased
      gradually during aging process, and the p-values between all three groups are
      less than 0.05. The plasma RCS concentration in different age groups showed a
      nonlinear association with age. The levels in the young group were slightly
      higher than the adult group (not significant) and lower than the old group (p <
      0.01). The protein carbonylation of erythrocyte membrane was positively
      correlated with plasma RCS concentration (p < 0.01), but not plasma thiols
      concentration. We conclude that higher levels of RCS, not lower levels of thiols,
      in plasma are a direct risk factor for the protein carbonylation of erythrocyte
      membrane. Owing to the decrease of thiols levels and increase of RCS levels
      during aging process, a shift from RCS-related redox allostasis to carbonyl
      stress would contribute to age-related biological dysfunction and even aging
      process.

PMID- 21187580
TI  - Erythrocyte deformability in morbid obesity before bariatric surgery. Influence
      of abdominal obesity.
AB  - Although there are several studies dealing with erythrocyte deformability (ED) in
      obese patients, research on this topic in morbidly obese subjects is scarce. In
      these studies ED seems to be decreased, although the cause remains unknown. A
      case-control study in 76 morbid obese subjects (23 women and 53 men, aged 44 +/-
      13 years) and in 79 normal-weight controls (30 women and 49 men, aged 43 +/- 13
      years) was undertaken. ED has been determined by ektacytometric techniques in a
      Rheodyn SSD, by means of the elongation index (EI) at 12, 30 and 60 Pascals,
      along with anthropometric, lipidic, metabolic and inflammatory parameters. EI was
      statistically lower in morbidly obese subjects than in controls at all the shear
      stresses tested (EI12: 47.3 +/- 2.14 vs. 47.9 +/- 2.07; p = 0.047, EI30: 52.16 +/
      2.1 vs. 53.12 +/- 1.4; p = 0.007, EI60: 53.9 +/- 2.4 vs. 55.2 +/- 2.50; p =
      0.001) as were anthropometric lipidic and inflammatory parameters (p < 0.001). In
      the bivariate correlation EI60 correlated negatively with most anthropometric,
      lipidic and inflammatory parameters. However, in the multivariate analysis, the
      case-control status was not significantly associated with EI60 and only
      triglycerides, glucose, hs-CRP and waist circumference were independently
      associated with EI60, constituting independent predictors of altered ED although,
      waist circumference, showed the highest statistical significance (p = 0.007). ED
      is decreased in morbidly obese subjects associated with insulin resistance and
      inflammation parameters although abdominal obesity seems to be of paramount
      importance in altering this rheological parameter.

PMID- 21187581
TI  - Nitric oxide metabolites and oxidative stress in mild essential hypertension.
AB  - Many papers have showed non univocal data about oxidative stress status and
      nitric oxide metabolites in essential hypertension. Considering this preamble we
      examined the total antioxidant status (TAS), the lipid peroxidation (LP),
      expressed as thiobarbituric acid-reactive substances (TBARS), the stable end
      products of nitric oxide (NOx) and LP/NOx ratio in 25 subjects with untreated
      mild essential hypertension. The obtained data show a significant increase in
      TBARS (p < 0.001) and NOx (p < 0.001) in hypertensives and no variation in TAS
      and in TBARS/NOx ratio. None of these parameters was statistically related to the
      metabolic parameters or to the blood pressure values. The high level of lipid
      peroxidation observed in this group of hypertensives suggests the timely and
      specific employment of antihypertensive and antioxidant agents while the NOx
      increase seems to confirm the inflammatory status accompanying this clinical
      condition.

PMID- 21187582
TI  - Visual search in mild cognitive impairment: a longitudinal study.
AB  - In the study of Alzheimer's disease, a multidisciplinary research approach has
      identified significant abnormality in several areas of visual and visual
      attention-related brain function in addition to those typically measured as part
      of clinical diagnosis. This raises the possibility that a similar approach
      applied to amnestic mild cognitive impairment (aMCI) will increase our
      understanding of its theoretical and clinical constructs, particularly if
      functions whose integrity is heterogeneous with respect to etiological outcome
      can be found. In this study we examined visual search performance (the brain's
      ability to search effectively throughout the environment for a particular object)
      in aMCI compared to healthy aging. Cross-sectionally, visual search performance
      in aMCI was significantly poorer than in healthy aging, with greater intra-group
      performance heterogeneity in the aMCI compared to the healthy older adult group.
      This outcome illustrates that although individuals within an aMCI group
      ostensibly have the same condition they can differ substantially with respect to
      the integrity of aspects of brain function. Such findings may have implications
      for the clinical management of the individual patient. The results from the
      longitudinal aspect of this study also illustrate how heterogeneity in the
      performance of brain operations other than memory in aMCI may help to inform the
      likelihood of their developing dementia, as those patients who were diagnosed
      with dementia within 2.5 years of baseline measurement showed significantly
      poorer visual search performance compared to those who did not.

PMID- 21187583
TI  - Profiles of Alzheimer's disease-related pathology in an aging urban population
      sample in India.
AB  - Systematic studies on Alzheimer's disease (AD)-related pathology that complement
      clinical and epidemiological data on dementia from low and middle income
      countries are rare. We report the first large study on AD-related pathology in
      autopsy service-derived brains from an urban center in India, a low/middle income
      country, and compare findings with a similar sample from New York. Amyloid-beta
      plaques and neurofibrillary tangles were assessed in 91 brain specimens derived
      from hospital autopsy cases from Mumbai, India (age 60+ years; mean age 71.1
      years, +/- 8.3 SD; range 60-107 years) and compared with identically examined age
      matched sample obtained in New York. These cases had no known clinical history of
      dementia. Our study showed that in comparison with the New York sample, the mean
      brain weight of the Mumbai sample was lower (p = 0.013) and mean diffuse plaque
      density was higher (p = 0.019), while differences in mean density and counts of
      neurofibrillary tangles and neuritic plaques were not statistically significant
      (p > 0.05). Our findings indicate that the burden of AD-related pathology was
      approximately equivalent in Mumbai and New York samples, which is at variance
      with expected lower AD-related lesion burden based on the
      clinical/epidemiological studies suggesting lower prevalence of AD in India.

PMID- 21187586
TI  - Copper in Alzheimer's disease: a meta-analysis of serum,plasma, and cerebrospinal
      fluid studies.
AB  - There is an ongoing debate on the involvement of systemic copper (Cu)
      dysfunctions in Alzheimer's disease (AD), and clinical studies comparing Cu
      levels in serum, plasma, and cerebrospinal fluid (CSF) of AD patients with those
      of healthy controls have delivered non-univocal and often conflicting results. In
      an attempt to evaluate whether Cu should be considered a potential marker of AD,
      we applied meta-analysis to a selection of 26 studies published in the
      literature. Meta-analysis is a quantitative method that combines the results of
      independent reports to distinguish between small effects and no effects, random
      variations, variations in sample used, or in different analytical approaches. The
      subjects' sample obtained by merging studies was a pooled total of 761 AD
      subjects and 664 controls for serum Cu studies, 205 AD subjects and 167 controls
      for plasma Cu, and of 116 AD subjects and 129 controls for CSF Cu. Our meta
      analysis of serum data showed that AD patients have higher levels of serum Cu
      than healthy controls. Plasma data did not allow conclusions, due to their high
      heterogeneity, but the meta-analysis of the combined serum and plasma studies
      confirmed higher Cu levels in AD. The analysis of CSF data, instead, revealed no
      difference between AD patients and controls.

PMID- 21187584
TI  - Homeostatic disinhibition in the aging brain and Alzheimer's disease.
AB  - In this article, we propose that impaired efficiency of glutamatergic synaptic
      transmission and a compensatory reduction in inhibitory neurotransmission, a
      process called homeostatic disinhibition, occurs in the aging brain and more
      dramatically in Alzheimer's disease (AD). Homeostatic disinhibition may help
      understand certain features of the aging brain and AD, including: 1) the
      increased risk for epileptic seizures, especially in the early phase of the
      disease; 2) the reduced ability to generate gamma-oscillations; and 3) the
      increase in neuronal activity as measured by functional MRI. Homeostatic
      disinhibition may be the major mechanism that activates cognitive reserve.
      Modulating neuronal activity may therefore be a viable therapeutic strategy in AD
      that can complement existing anti-amyloid strategies. Specifically, enhancing
      endogenous glutamatergic synaptic transmission through increased co-agonist
      signaling or through positive allosteric modulation of metabotropic glutamatergic
      receptors appears as an attractive strategy. Alternatively, further reduction of
      GABAergic signaling may work as well, although care has to be taken to prevent
      epileptic seizures.

PMID- 21187585
TI  - Effect of cerebral amyloid angiopathy on brain iron, copper, and zinc in
      Alzheimer's disease.
AB  - Cerebral amyloid angiopathy (CAA) is a vascular lesion associated with
      Alzheimer's disease (AD) present in up to 95% of AD patients and produces MRI
      detectable microbleeds in many of these patients. It is possible that CAA-related
      microbleeding is a source of pathological iron in the AD brain. Because the
      homeostasis of copper, iron, and zinc are so intimately linked, we determined
      whether CAA contributes to changes in the brain levels of these metals. We
      obtained brain tissue from AD patients with severe CAA to compare to AD patients
      without evidence of vascular amyloid-beta. Patients with severe CAA had
      significantly higher non-heme iron levels. Histologically, iron was deposited in
      the walls of large CAA-affected vessels. Zinc levels were significantly elevated
      in grey matter in both the CAA and non-CAA AD tissue, but no vascular staining
      was noted in CAA cases. Copper levels were decreased in both CAA and non-CAA AD
      tissues and copper was found to be prominently deposited on the vasculature in
      CAA. Together, these findings demonstrate that CAA is a significant variable
      affecting transition metals in AD.

PMID- 21187587
TI  - Association between bone mineral density and the risk of Alzheimer's disease.
AB  - Alzheimer's disease (AD) and osteoporosis are common chronic degenerative
      disorders which are strongly associated with advanced age. Some studies suggest
      that low bone mineral density (BMD) is related to the increased risk of AD. We
      conducted a 5-year prospective study to exam the association between BMD and the
      risk of AD in a cohort of Chinese elderly people. Of 3263 community residents
      aged 65 years and over, 2019 were enrolled into the study and followed up
      annually for 5 years. At baseline demographic data, smoking and drinking status,
      medical history, cognitive status, and blood samples were collected. BMD was
      measured by dual energy X-ray absorptiometry (DEXA) scanning at baseline and
      during follow-up. Cox proportional hazards analysis was used to evaluate the
      association with BMD and incidence of AD. Over the follow-up of 5 years, AD
      developed in 132 subjects. Baseline BMD, bone loss rate, current smoking, and
      daily drinking were associated with increased risk of AD, while higher baseline
      plasma leptin level was associated with decreased risk of AD, in both women and
      men. Low BMD and increased loss rate of BMD were associated with higher risk of
      AD. Cigarette smoking, alcohol drinking, and lower leptin level are risk factors
      for AD. Uncovering the relation linking osteoporosis and AD is important for
      understanding the pathogenesis and developing therapeutic strategies for these
      two common disorders afflicting elderly people.

PMID- 21187588
TI  - Describing the dying days of "Alzheimer's disease".

PMID- 21187589
TI  - [Teriparatide: human recombinant parathyroid hormone (1-34) as a daily
      subcutaneous injection].
AB  - Teriparatide is a preparation of human parathyroid hormone (PTH) (1-34). It has
      been approved as an agent for stimulating bone formation in many foreign
      countries, including Europe and the United States. In Japan, it was approved in
      July this year. In nonclinical studies, teriparatide was shown to have a unique
      bone formation-stimulating effect not seen in existing drugs. In domestic and
      overseas clinical studies, teriparatide was shown to have strong effects in
      increasing BMD, promoting remodeling of bone microstructure and suppressing the
      onset of fracture. Furthermore, teriparatide can increase BMD through stimulation
      of bone formation regardless of the nature of prior treatment or the
      presence/absence of responses to prior treatment. With these features,
      teriparatide is expected to serve as a first-line drug for management of patients
      with osteoporosis at elevated risk for fracture.

PMID- 21187590
TI  - [Therapeutic agents for disorders of bone and calcium metabolism: Weekly
      subcutaneous injection of teriparatide.].
AB  - Daily subcutaneous injection of parathyroid hormone (1-34) (teriparatide; TPTD),
      which is widely used regimen for osteoporotic patients in many countries, exerts
      strong action on increment of bone volume and prevention of fracture, but
      activated osteoclastic bone resorption might also occur in this regimen. In
      contrast, once weekly subcutaneous injection of TPTD, which is being developed in
      Japan, efficiently increase bone mass by stimulating bone formation without
      apparent bone resorption. Recent study demonstrated that weekly injection of TPTD
      increase bone strength in primates by improving bone mass, bone structure and
      bone quality. In addition, the weekly injection of TPTD increase lumber spine
      bone mineral density in osteoporotic patients as well as the daily injection.
      These data suggest that the weekly injection of TPTD is a useful regimen, which
      discriminate from the daily injection of TPTD.

PMID- 21187591
TI  - [Development of hPTHrP (1-36) as an anabolic therapeutic agent for osteoporosis].
AB  - Parathyroid hormone-related protein (PTHrP) shares the same receptor (PTH/PTHrP
      recoptor) with parathyroid hormone (PTH) to generate common intracellular
      signals. Thus, systemic actions of PTHrP are seemed to be essentially the same as
      those of PTH, although PTHrP plays its physiological roles in cartilage
      development and smooth muscle contraction as a local factor. Subcutaneous
      administration of PTH once a day demonstrates anabolic effects on bone and has
      been established to be an effective therapeutic modality for patients with severe
      osteoporosis to increase bone mineral density and then prevent fracture
      substantially. According to preclinical and some clinical data, daily
      subcutaneous injection of human PTHrP (1-36) could stimulate bone formation
      without a substantial increase in bone resorption or expected adverse events such
      as hypercalcemia. Thus, human PTHrP (1-36) is one of the promising drugs for
      treatment of osteoporosis.

PMID- 21187592
TI  - [Bazedoxifene as a new-generation SERM].
AB  - Bazedoxifene is a new-generation SERM with a novel chemical structure, which has
      been developed to provide improved efficacy on the bone and the lipid profile, as
      well as improved safety for breast and endometrial tissues. A statistically
      significant 42% reduction in the incidence of new vertebral fractures has been
      reported with bazedoxifene treatment in an overseas phase III trial, equal to
      that reported with the bisphosphonates and raloxifene. A significant reduction in
      the incidence of non-vertebral fractures was also shown with bazedoxifene,
      compared to placebo and raloxifene in the high-risk population in a post-hoc
      analysis. These data suggest that bazedoxifene could be more effective in
      reducing the risk for non-vertebral fractures than raloxifene. Bazedoxifene has
      demonstrated a favorable safety and tolerability profile with no significant
      differences observed among the treatment groups in coronary artery events,
      cerebrovascular events, and overall death rates. The incidence of adverse events,
      such as VTEs, hot flushes and leg cramps, reported as a class effect of the
      SERMs, were higher with bazedoxifene than with placebo, but was similar to that
      with raloxifene. Bazedoxifene is thus expected to become an important new option
      for the treatment of postmenopausal osteoporosis in Japan.

PMID- 21187593
TI  - [Anti-RANKL monoclonal antibody Denosumab (AMG162)].
AB  - Denosumab is a fully human monoclonal antibody to the receptor activator of
      nuclear factor-kappaB ligand (RANKL) which blocks its binding to RANK, inhibiting
      the development and activity of osteoclasts, followed by suppression of bone
      resorption. Denosumb given subcutaneously twice yearly for 3 years was associated
      with a reduction in the risk of vertebral, nonvertebral and hip fractures but not
      with serious adverse events in women with osteoporosis. New horizon would be
      brought about by Denosumab, new molecular targeting pharmaceutics in the
      treatment of osteoporosis as well as rheumatoid arthritis and metastatic bone
      diseases.

PMID- 21187594
TI  - [Eldecalcitol (ED-71)].
AB  - ED-71 is a new vitamin D receptor ligand, bearing a hydroxypropoxy substituent at
      the 2beta-position of 1alpha, 25 (OH) (2)D(3). In ovariectomized rats, ED-71
      increased vertebral bone mass and bone strength by inhibiting bone resorption and
      maintaining bone formation. In randomized, placebo-controlled, double-blinded
      clinical trial for osteoporotic subjects, ED-71 increased lumber vertebral and
      hip bone mineral density independently vitamin D status. Furthermore, ED-71 may
      have a better osteoprotective effect than alfacalcidol and suggest that ED-71 may
      serve as a new generation of active vitamin D with anti-fracture efficacy in
      osteiporotic subjects.

PMID- 21187595
TI  - [Odanacatib (MK-0822)].
AB  - Bone homeostasis is maintained by delicate balance between bone resorption by
      osteoclasts and bone formation by osteoblasts. Bisphosphonates are widely used
      nowadays by suppressing bone resorption to treat patients with osteoporosis,
      which results from high bone turnover, causing excessive bone resorption phase.
      While bisphosphonates increase bone mineral density and improve back pain due to
      spinal compression fracture, they may have some problems such as osteonecrosis of
      jaw and excessive suppression of bone turnover. Cathepsin K inhibitor, which has
      a new mechanism in addition to function of suppressing bone resorption, is
      recently focused. Cathepsin K is a protease which specifically expresses in
      osteoclasts and plays an important role in resolution of bone collagen. Cathepsin
      K inhibitor has a potential of inhibiting bone resorption without suppressing
      bone formation and could be an attractive therapeutic target of osteoporosis.

PMID- 21187596
TI  - [New approach for osteoporosis treatment: cathepsin K inhibitor, ONO-5334].
AB  - ONO-5334, an orally-administered low-molecular compound, is a selective synthetic
      inhibitor of cathepsin K which is specifically expressed in osteoclasts and has a
      critical role in bone-collagen degradation. ONO-5334 is being developed by Ono
      Pharmaceutical Co., Ltd. as a possible therapeutic agent for osteoporosis. ONO
      5334 has been shown to prevent the decrease in bone mineral density (BMD) in the
      ovariectomized cynomolgus monkey osteoporosis model. In a 12-month clinical study
      with postmenopausal osteopenia or osteoporosis, ONO-5334 showed a significant
      increase in BMD compared with placebo and a similar magnitude of suppression on
      bone resorption compared with the current well known anti-resorptive agents,
      bisphosphonates, but with little or no suppression on bone formation. There were
      no clinically relevant safety concerns identified in this study. Whether this
      mechanism of action may result in more potent anti-fracture efficacy accompanied
      by better bone quality in long term use of ONO-5334 is of significant interest.

PMID- 21187597
TI  - [Minodronic acid- its clinical efficacy and prospects for once-a-month dosing
      regimen].
AB  - Minodronic acid has been developed and approved for the treatment of osteoporosis
      in Japan. It was reported that daily 1 mg minodronate for 24 months reduced the
      risk of vertebral fractures. It was also reported that minodronic acid suppressed
      the risk of vertebral fractures in patients aged 75 years or older in the same
      way as in patients aged less than 75 years. Monthly 50 mg minodronate is now
      under development for the treatment of osteoporosis in Japan. It is expected that
      monthly administration would improve medication adherence and, as a result,
      incidence of fragility fractures will be reduced with the improvement of quality
      of life in the elderly.

PMID- 21187598
TI  - [Ibandronate].
AB  - Ibandronate is a potent nitrogen-containing bisphosphonate and is a convenient
      therapeutic drug for osteoporosis because ibandronate can be administrated once a
      month or at much longer interval by orally or intravenously (bolus injection). In
      BONE study, that is a large-scale pivotal study on fracture with osteoporosis
      patients, efficacy to prevent the incidence of new vertebral fracture was shown
      in both regimen of 2.5 mg daily and 20 mg intermittent oral administration. Then
      the clinical development by new intermittent dosing method was accelerated,
      aiming at the improvement of compliance/adherence which is one of the issues when
      the bisphosphonates are administered orally. Both monthly oral and quarterly
      intravenous bolus injectable formulations of ibandronate for osteoporosis already
      have been launched in the U.S., EU and other countries. In parallel, both
      formulations for osteoporosis have being also developed in Japan. We expect
      ibandronate will provide a new option for the treatment of osteoporosis in Japan.

PMID- 21187599
TI  - [Antagonist for calcium-sensing receptor. JTT-305/MK-5442].
AB  - Calcium-sensing receptor (CaSR) is a G protein-coupled receptor which was
      identified as a molecule that medicates the suppression of parathyroid hormone
      (PTH) secretion by extracellular Ca. Calcilytics are chemicals that enhance PTH
      secretion by antagonizing CaSR. JTT-305/MK-5442 is one of calcilytics made in
      Japan and is considered to be used as a bone anabolic agent through its
      stimulatory effect on PTH secretion. It is reported that JTT-305/MK-5442
      increased lumbar bone mineral density by a placebo-controlled trial. However,
      further studies with more subjects are necessary to establish the clinical
      utility of JTT-305/MK-5442.

PMID- 21187600
TI  - [Anti-sclerostin antibodies].
AB  - Sclerostin is a secreted protein from osteocytes that inhibits Wnt signaling. Wnt
      signalling plays important roles in osteoblastic differentiation hence bone
      formation. Therefore, inhibition of sclerostin promotes bone formation. A
      monoclonal antibody has been generated against sclerostin, which has been shown
      to stimulate bone formation and increase bone volume in rodents and primates.
      Preliminary data on human showed this antibody increases markers for bone
      formation. Clinical phase 2 study using this antibody in postmenopausal
      osteoporosis was initiated in 2009, of which results are anticipated.

PMID- 21187601
TI  - [ASBMR 2010 report. Meeting report on the ASBMR. Obstacles in medicine for
      osteoporosis].
AB  - The 32nd ASBMR meeting had been held in Toronto, Ontario, Canada from October
      15th to 19th 2010. In clinical session, there were several reports as to novel
      medicine for osteoporosis and atypical femoral fracture as an adverse event of
      bisphosphonates. Furthermore, relationship between bone and brain attracted great
      attention in basic science.

PMID- 21187602
TI  - [ASBMR 2010 report. Meeting report on the ASBMR. Topics on basic research in
      ASBMR 2010].
AB  - This overview would introduce some of topics from the 32nd annual meeting of
      ASBMR held in Toronto, Canada from October 15th to 19th, 2010; especially
      focusing on orally presented basic researches and state-of-the-art lecture.

PMID- 21187603
TI  - [ASBMR 2010 report. Meeting report on the ASBMR: clinical topics in ASBMR 2010 at
      Toronto].
AB  - The 32nd meeting of ASBMR was held in Toronto, Ontario, Canada from October 15th
      to 19th, 2010. Some of the clinical topics from the meeting are summarized.

PMID- 21187604
TI  - [Measurement of bone mineral density is necessary for monitoring of
      bisphosphonate treatment].
AB  - The treatment efficacy of antiresorptive therapy, including bisphosphonates, is
      not fully accounted for by change in bone mineral density (BMD). The 1-year
      increases in hip BMD were reported to be associated with a reduction in spine
      fracture by using the data from FIT trial, but the changes in spine BMD that was
      greater than hip BMD were not associated with the risk of spine, non-spine, or
      hip fracture. On the other hand, the diagnosis of osteoporosis is made mainly by
      measurement of BMD. In this sense, BMD measurement is thought to be useful in
      will improvement for the treatment of the patients.

PMID- 21187605
TI  - [Measurement of bone mineral density is unnecessary for monitoring of
      bisphosphonate treatment].
AB  - A monitoring period in osteoporosis treatment should be considered in accordance
      with the efficacy of medicine as well as the precision of monitoring tool,
      because a significant bone gain should be larger than the precision error of the
      measurement. Regarding bisphosphonate treatment in osteoporosis, 2-5 years'period
      is required to detect a significant change in bone mineral density (BMD) using
      dual-energy x-ray absorptiometry. Furthermore, the degree of increase in BMD by
      bisphosphonate treatment cannot account for the degree of reduction in the risk
      of fracture. It therefore makes no sense to determine how much BMD increases
      during the treatment.

PMID- 21187606
TI  - The intricacies of research work.

PMID- 21187607
TI  - Predicting the actual length of premolar teeth on the basis of panoramic
      radiology.
AB  - BACKGROUND: Panoramic radiography is one of the most common techniques for
      evaluating the jaw bones and associated structures. AIM: The aim of the study was
      to predict the actual length of the premolar teeth, based on measurements taken
      on a panoramic radiograph. MATERIALS AND METHODS: This study was done in two
      stages. In the first stage, the actual and panoramic lengths of 102 teeth of
      orthodontic patients were measured and compared. In the next stage, the actual
      and radiographic vertical lengths of four metal balls placed in the molar and
      first premolar areas of 27 patients, referred to radiography clinic were also
      analyzed. Comparison of the mean magnification between the two methods was
      performed by one-sample T-test and P<0.05 was considered as statistically
      significant. RESULTS: The total magnification of the premolar region in the
      vertical plane in the tooth length measurement method was 17.39%, while the same
      in the metal markers method was 27.39%. The upper teeth showed larger
      magnification than the lower teeth in the vertical plane. Similarly, the
      magnification and distortion of the metal markers in the horizontal plane were
      significantly more than this in the vertical plane and also their magnification
      and distortion in the molar region were more than this in the premolar region.
      The actual length of the premolar teeth can be estimated by using a suitable
      regression formula. CONCLUSION: Panoramic radiography can be used for calculating
      the actual length of premolar teeth.

PMID- 21187608
TI  - Clinical investigation of mucosal thickness stability after soft tissue grafting
      around implants: a 3-year retrospective study.
AB  - PURPOSE: To assess the long-term stability of gingival grafts placed around
      dental implants at the time of second surgery uncovering and to further
      investigate the association between mucosal thickness (MTh) by demographic
      variables and clinical investigation. MATERIALS AND METHODS: Fourteen patients
      with submerged dental implants covered by inadequate keratinized mucosa were
      studied. The subjects underwent a periimplant plastic surgery (PPS) at the second
      stage dental implant surgery and free gingival autograft orsubepithelial
      connective tissue graft were used according to the patients' clinical situation.
      Clinical measurement of MTh was assessed by bone sounding with a periodontal
      probe using customized acrylic stents andthe values were recorded at baseline
      (day of graft) and at 0.5, 1.5, 4, 12, 24 and 36 months after grafting. RESULTS:
      At 12 months postoperatively, the mean MTh was 2.89 mm, with a mean additional
      increase of 1.75 mm when compared with baseline (P=0.0001). No statistically
      significant differences in MTh were found between the 12- and the 36-month
      observations (P=0.09). In addition, at 36 months, a thin mucosa was associated
      with a greater increase in the MTh compared with a thick mucosa (2.14 and 0.64
      mm, respectively, P=0.006). Similarly, the mandibular sites were associated with
      a greater increase in the MTh in comparison with the maxillary sites (2.17 and
      0.81 mm, respectively; P=0.02). CONCLUSIONS: Within the limitations of this
      investigation, the data suggest that PPS at the second-stage dental implant
      surgery could results in additional increases in MTh, especially when it is
      performed in areas where the mucosa is of a thin biotype.

PMID- 21187609
TI  - Using zero inflated models to analyze dental caries with many zeroes.
AB  - AIM: The study aimed to analyze and determine the factors associated with dental
      caries experience contains many zeros by zero inflated models. DESIGN: A cross
      sectional design was employed using clinical examination and questionnaire with
      interview method. MATERIALS AND METHODS: A study was conducted during March
      August 2007 in Dharwad, Karnataka, India, involved a systematic random samples of
      1760 individuals aged 18-40 years. The dental caries examination was carried out
      by using DMFT index (i.e. Decayed (D), Missing (M), Filled (F)). The DMFT index
      data contains many zeros were analyzed with Zero Inflated Poisson (ZIP) and Zero
      Inflated Negative Binomial (ZINB) models. RESULTS: The study findings indicated,
      the variables such as family size, frequency of brushing and duration of change
      of toothbrush were positively associated with dental caries. But the variable the
      frequency of sweet consumption is negatively associated with dental caries
      experience in Zero Inflated Poisson (ZIP) and Zero Inflated Negative Binomial
      (ZINB) models. CONCLUSIONS: The ZIP model is a very good fit over the standard
      Poisson model and the ZINB is the better statistical fit compared to the Negative
      Binomial model. The Zero Inflated Negative Binomial model is better fit over the
      Zero Inflated Poisson model for modeling the DMF count data.

PMID- 21187610
TI  - Estimation of salivary amylase and total proteins in leukemia patients and its
      correlation with clinical feature and radiographic finding.
AB  - BACKGROUND: Leukemia is a fatal disease. The oral manifestations of the leukemias
      occur early in the course of the disease and these oral features can at times act
      as a diagnostic indicator. Saliva has been used as a diagnostic aid in a number
      of systemic diseases. MATERIALS AND METHODS: In our study, samples of
      unstimulated saliva of 30 leukemia patients who were not on chemotherapy were
      collected and analyzed for salivary amylase and total protein. The oral
      manifestations and radiographic changes (OPG) were recorded. The correlation
      between the oral manifestations and the salivary components (salivary amylase and
      total protein) was assessed for prognostic significance. RESULTS: In the present
      study when the mean values of salivary amylase (1280+/-754 U/ml) and total
      protein (647.2+/-320.7 mg%) were compared with that in control subjects. There
      was a statistically significant difference for amylase levels (P<.05). On
      intraoral examination the study subjects showed pallor, gingivitis, gingival
      enlargement, petechiae, and ecchymosis. On the OPG, the radiographic features
      included generalized rarefaction of bone (20%), thinning of lamina dura (3.4%),
      generalized alveolar crest bone resorption (30%), thinning of walls of alveolar
      crypts (6.7%), besides others, e.g., periapical abscess (10%). CONCLUSIONS: The
      saliva of leukemic patients demonstrated obvious changes in composition. A rise
      in salivary amylase and total protein levels was evident, with the increase in
      amylase levels being statistically significant.

PMID- 21187611
TI  - Inner canthal distance and golden proportion as predictors of maxillary central
      incisor width in south Indian population.
AB  - OBJECTIVES: Even though the constant relation of golden proportion and inner
      canthal distance (ICD) with the width of the maxillary central incisor (CIW) has
      been found in European population, it may not be applied to Indian population as
      we differ from Europeans racially and genetically. Hence, this study was carried
      out with the objectives of determining if these parameters are applicable to our
      population also. MATERIALS AND METHODS: Three hundred south Indian subjects
      between 18 and 26 years of age, free from facial and dental deformities were
      examined. Inner canthus of each eye was used as soft tissue landmark. The
      maxillary central incisors were measured at the contact point area with the help
      of digital vernier caliper. The CIW was also calculated using golden proportion
      ratio to obtain the calculated central incisor width. A comparison was made with
      measured width. Statistical analyses were done to identify any significant
      difference using "Z" tests. Pearson's Correlation Coefficient test was used to
      evaluate the measured and the calculated width of the central incisor. RESULTS:
      ICD and the width of two maxillary incisors were in golden proportion in south
      Indian population. Also, ICD when multiplied by a decreasing function value of
      the golden proportion and divided by 2 is a reliable predictor of determining
      CIW. CONCLUSION: As in the European population, the ICD and the golden proportion
      are reliable predictors for determining the width of the maxillary central
      incisors in the south Indian population also.

PMID- 21187612
TI  - Comparison of manual and physiologically molded denture bases in complete denture
      wearers.
AB  - BACKGROUND AND OBJECTIVES: In complete denture wearers, the accumulation of food
      in the buccal vestibule is one of the factors causing discomfort to the patient.
      This study was conducted to evaluate the effect of mandibular denture buccal
      flange on food retention and to correlate between varying angulations of buccal
      flange of mandibular denture on food retention. MATERIALS AND METHODS: Complete
      dentures were fabricated and the mandibular complete denture was duplicated. The
      existing (unduplicated) manually molded and physiologically molded dentures were
      tested for food retention. Twenty test particles having a diameter of 2+/-0.2 mm
      were placed on the middle part of the buccal flange and the subjects were
      instructed to expel the test particles by performing only functional movements of
      the buccal musculature. The numbers of residual test particles in the buccal
      vestibule were counted after 30s. The angulations of the denture buccal flange
      (duplicated) were measured with an optical bevel protractor and trimmed to 50
      degrees  and the food retention test was performed. Similar tests were performed
      at 60 degrees , 70 degrees  and 80 degrees  angulations. The data were evaluated
      using the Pearson correlation coefficient, One-way ANOVA test and Wilcoxon signed
      rank test. RESULTS: The difference between the residual scores of manually molded
      and physiologically molded denture base was not significant. The difference
      between the residual scores at different angulations of the buccal flange of the
      denture was significant. CONCLUSION: Only the slope of the flange significantly
      affects the ability of subjects to expel the test particles.

PMID- 21187613
TI  - Effect of prepolymerized composite megafiller on the marginal adaptation of
      composite restorations in cavities with different C-factors: an SEM study.
AB  - AIM: To evaluate the effect of prepolymerized custom-made composite megafiller
      and configuration factors (C-factor) on marginal adaptation of resin composite
      restorations. MATERIALS AND METHODS: Forty extracted human mandibular molars were
      divided into four experimental groups consisting of 10 samples each. In groups I
      and III, class V (configuration factor 5) and in groups II and IV, class II box
      shaped cavities (configuration factor 2) were prepared. Groups I and II were
      restored with a nanofilled composite (FiltekTM Z350 3M ESPE, St Paul, MN, USA)
      placed in horizontal increments. In groups III and IV, preformed composite
      megafiller was placed and cavities were restored with nanofilled composite Z-350.
      After curing, the samples were finished and prepared for examination under low
      vacuum scanning electron microscope. The data were analyzed with one-way analysis
      of variance. The significance between the individual groups was calculated by
      Post hoc test using the Holm-Sidak method ( P<=0.05). RESULTS: The marginal gap
      values in groups III and IV were significantly lower than in groups I and II,
      respectively ( P<=0.05). Minimum gap values were seen in group IV. CONCLUSION:
      Use of prepolymerized composite megafiller and a lower C-factor decreased the
      marginal gaps between the tooth and composite restorations.

PMID- 21187614
TI  - Three-dimensional finite element analysis of the stress distribution pattern in
      the design modifications of U-shaped palatal major connector.
AB  - BACKGROUND: The U-shaped maxillary major connector is considered to be the least
      desirable design by many prosthodontists as it lacks rigidity, which is a primary
      requisite for a major connector. AIMS AND OBJECTIVES: Design modifications in the
      U-shaped palatal major connector are desired because it lacks rigidity. The study
      also aimed to determine the best design when a U-shaped palatal major connector
      is indicated for clinical use. MATERIALS AND METHODS: The normal design and the
      design-modified models (modification 1, 2, 3, 4) were loaded at the functional
      cusps of the premolars and the molars with a magnitude of 200 N, 250 N and 300 N
      at angulations of 60 o and 90 o on both sides of the maxillary arch. Results for
      each loading were obtained as stress distribution colored images and numerical
      values were recorded. A three-dimensional finite element analysis study of the
      design-modified models was performed using two finite element softwares, namely
      PRO-E and IDEAS. RESULTS: The least stress value of 7.86 Megapascals (MPa) at 200
      N, 60 o was recorded for the double-thickness design, followed by design 1, which
      was 8.03 MPa. The least stress value for the palatal mucosa and ligament was
      provided by design modification 1 (0.5 mm-thick U-shaped connector, 9 mm
      anteroposteiorly, 14.6 mm laterally), which was 9.78 MPa and 2.98 MPa,
      respectively. CONCLUSION: The double-thickness group exhibited the least internal
      stress for the U-shaped major connector. However, it delivered the greatest
      stress to the palatal mucosa and the periodontal ligaments.

PMID- 21187615
TI  - An in vitro study of antibacterial effect of calcium hydroxide and chlorhexidine
      on Enterococcus faecalis.
AB  - AIM: To evaluate and compare the antibacterial effects of chlorhexidine and
      calcium hydroxide on Enterococcus faecalis. MATERIALS AND METHODS: Root canal
      treatment involves a number of steps. In spite of all the steps done thoroughly,
      root canal treatment might fail due to the remnant microbes. Of all such
      bacteria, E. faecalis is found in failed root canals. The study tests the
      antibacterial activity of various intracanal medicaments. Agar diffusion test was
      used to evaluate the antibacterial effects of the following antibacterial agents:
      i. hexidine:0.2% chlorhexidine gluconate; ii. periogard:0.12% chlorhexidine
      gluconate; iii. calcium hydroxide powder plus sterile water; iv. metapaste plus
      sterile water; v. calcium hydroxide plus hexidine; vi. calcium hydroxide plus
      periogard; vii. metapaste plus hexidine; viii. metapaste plus periogard. The size
      of zones of inhibition was measured. RESULTS: The average size of zones of
      inhibition after 72 hours were hexidine: 5 mm; periogard: 4.25 mm; calcium
      hydroxide plus sterile water: 0.5 mm; metapaste plus sterile water: 0.5 mm;
      calcium hydroxide plus hexidine: 4.7 mm; calcium hydroxide plus periogard: 4 mm;
      metapaste plus hexidine: 4.65 mm; metapaste plus periogard: 4 mm. Results were
      subjected to statistical analysis using one way analysis of variance and Tukey
      tests. CONCLUSION: Chlorhexidine and its preparations are more potent
      antibacterial agents against E. faecalis in comparison to calcium hydroxide.

PMID- 21187616
TI  - Fluoride and bacterial content of bottled drinking water versus municipal tap
      water.
AB  - BACKGROUND: Water is a divine gift. People quench their thirst without
      questioning the source of water. But, apprehension about contaminants in
      municipal water supplies along with increased fear of fluorosis made bottled
      drinking water as one of the important tradable commodities. OBJECTIVES: The
      objectives of the study were to determine and compare the fluoride and bacterial
      contents of commercially available bottled drinking water and municipal tap water
      in Davangere city, Karnataka. MATERIALS AND METHODS: Fifty samples of 10
      categories of bottled drinking water with different batch numbers were purchased
      and municipal water from different sources were collected. Fluoride levels were
      determined by an ion-selective electrode. Water was cultured quantitatively and
      levels of bacteria were calculated as colony-forming units (CFUs) per milliliter.
      RESULTS: Descriptive analysis of water samples for fluoride concentration was in
      the range of 0.07-0.33 for bottled drinking water, Bisleri showing the highest of
      0.33. A comparison of the mean values of microbial count for bottled drinking
      water with that of municipal tap water showed no statistically significant
      difference, but was more than the standard levels along with the presence of
      fungus and maggots. CONCLUSION: The fluoride concentration was below the optimal
      level for both municipal tap water and bottled drinking water. CFUs were more
      than the recommended level in both municipal tap water and bottled drinking
      water.

PMID- 21187617
TI  - Morphology of collagen fibers and elastic system fibers in actinic cheilitis.
AB  - BACKGROUND: Actinic cheilitis (AC) is a premalignant condition intimately related
      to exposure of the lips to sun rays. AIM: The objective of this study was to
      evaluate the elastic and collagen fibers in the lamina propria of AC. The degree
      of epithelial atypia was correlated with the quantity of elastic and collagen
      fibers. MATERIALS AND METHODS: Fifty-one cases were investigated. One slide was
      stained with hematoxylin-eosin for the evaluation of atypia, the second was
      stained with Weigert's resorcin-fuchsin for the assessment of elastic fibers, and
      the third slide was stained with Mallory's trichrome for the analysis of collagen
      fibers. RESULTS: Ordinal logistic regression analysis revealed a significant
      correlation between the presence of atypia and collagen fibers (P<0.05).
      CONCLUSIONS: It was concluded that there seems to be a reduction in the quantity
      of collagen fibers in cases of moderate and severe atypia. No correlation was
      observed between the degradation of elastic system fibers and the grade of
      dysplasia.

PMID- 21187618
TI  - Comparison of 2% chlorhexidine and 5.25% sodium hypochlorite irrigating solutions
      on postoperative pain: a randomized clinical trial.
AB  - AIM: To compare the levels of postoperative pain after cleaning and shaping of
      root canals using two different root canal irrigants for debridement. MATERIALS
      AND METHODS: Forty patients with irreversible pulpitis, pulp necrosis and non
      vital teeth exhibiting acute apical periodontitis requiring root canal treatment
      were included. At random, canals were cleaned and shaped with the following
      protocols. 2% chlorhexidine solution in group I and 5.25% sodium hypochlorite
      solution in group II were used as an irrigants. Access cavities were closed with
      a sterile cotton pellet and cavit. The patients recorded degree of pain at
      various time intervals after cleaning and shaping on a visual analogue scale for
      1 week. RESULTS: The mean pain score for group I was between 0.65 and 3.35 and
      for group II was between 0.95 and 4.50. There was significant difference in the
      pain level between the two groups only at 6 th hour postoperatively (P<0.05) and
      the pain was more in sodium hypochlorite group. CONCLUSIONS: More pain was
      present in teeth irrigated using 5.25% sodium hypochlorite when compared to that
      in teeth irrigated using 2% chlorhexidine solution. Significant difference in
      pain level was present only at 6th hour postoperatively, and at all other periods
      (24 th hour, 4 th and 7 th days) there was no significant difference in pain
      level between the two groups.

PMID- 21187619
TI  - Fluoride content in bottled drinking waters, carbonated soft drinks and fruit
      juices in Davangere city, India.
AB  - BACKGROUND: The regular ingestion of fluoride lowers the prevalence of dental
      caries. The total daily intake of fluoride for optimal dental health should be
      0.05-0.07 mg fluoride/kg body weight and to avoid the risk of dental fluorosis,
      the daily intake should not exceed a daily level of 0.10 mg fluoride/kg body
      weight. The main source of fluoride is from drinking water and other beverages.
      As in other countries, consumption of bottled water, juices and carbonated
      beverages has increased in our country. OBJECTIVE: To analyze the fluoride
      content in bottled water, juices and carbonated soft drinks that were commonly
      available in Davangere city. MATERIALS AND METHODS: Three samples of 10
      commercially available brands of bottled drinking water, 12 fruit juices and 12
      carbonated soft drinks were purchased. Bottled water and carbonated soft drinks
      were stored at a cold place until fluoride analysis was performed and a clear
      juice was prepared using different fruits without the addition of water. Then,
      the fluoride analysis was performed. RESULTS: The mean and standard deviation of
      fluoride content of bottled water, fruit juices and carbonated soft drinks were
      measured, which were found to be 0.20 mg (+/-0.19) F/L, 0.29 mg (+/-0.06) F/L and
      0.22 mg (+/-0.05) F/L, respectively. CONCLUSION: In viewing the results of the
      present study, it can be concluded that regulation of the optimal range of
      fluoride in bottled drinking water, carbonated soft drinks and fruit juices
      should be drawn for the Indian scenario.

PMID- 21187620
TI  - Alkaline phosphatase as a periodontal disease marker.
AB  - BACKGROUND: The potential of alkaline phosphatase (ALP) as an important
      diagnostic marker of gingival crevicular fluid (GCF) has been the subject to
      investigation since 1970. ALP is stored in specific granules and secretory
      vesicles of the neutrophils and is mainly released during their migration to the
      site of infection. It is also present in bacteria within dental plaque,
      osteoblasts and fibroblasts. It has, thus, become important to elucidate whether
      GCF levels of ALP are potential measures of the inflammatory activity occurring
      in the adjacent periodontal tissues. OBJECTIVE: The aim of this study was to
      assess the total activity of ALP in the GCF collected from healthy sites, sites
      with gingivitis and with chronic adult periodontitis. An attempt was also made to
      establish the correlation of ALP activity with plaque index, gingival index,
      bleeding index and probing depth. MATERIALS AND METHODS: A total of 18 patients
      were divided into three groups: viz., healthy sites, Group I; gingivitis, Group
      II; chronic periodontitis, Group III. Clinical parameters like plaque index,
      bleeding index, gingival index and probing depth were recorded. The ALP level in
      GCF of all three groups was determined by spectrophotometric analysis. RESULTS:
      Total enzyme activity of ALP was significantly higher in periodontitis as
      compared with that in healthy and gingivitis sites, and was significantly and
      positively correlated with probing depth. CONCLUSION: ALP can be considered as a
      periodontal disease marker as it can distinguish between healthy and inflamed
      sites. However, to better define its capacity for periodontal diagnosis,
      additional longitudinal studies are required.

PMID- 21187621
TI  - Evaluation of biocompatibility of Targis Dentin and Artglass by using
      subcutaneous implantation test.
AB  - INTRODUCTION: Biocompatibility of a crown-bridge material is as important as its
      physical and mechanical properties. It is also one of the most important factors
      for the long-lasting clinical success of that restoration. It directly contacts
      the vital prepared tooth and that is the reason it has to be nontoxic to the
      local tissues, such as the pulp, gingiva, or the rest of the body. Materials with
      different physical properties are used in the conventional fixed prosthodontic
      restorations. Recently, metal-free systems that are reinforced with fibers have
      been improved for crown and bridge restorations. These new composite systems have
      the advantages of both ceramic and polymer chemistry. MATERIALS AND METHODS: In
      this research, biocompatibility of two ceramic-polymer-based prosthetic materials
      (Targis Dentin(r) and Artglass Dentin(r) ) was studied using a subcutaneous
      implantation test on rats. Initially (15 th day) mild inflammatory reactions were
      observed in tissues, which directly contacted the Artglass, Targis, and control
      tubes. These probably originated from the surgical traumas. After the 90th day of
      implantation, these reactions resolved and healthy, well-organized fibrous
      connective capsules were seen around the implants. RESULTS: Initially (15 th day)
      mild inflammatory reactions were observed in tissues, which directly contacted
      the Artglass, Targis, and control tubes. These probably originated from the
      surgical traumas. After the 90 th day of implantation, these reactions resolved
      and healthy, well-organized fibrous connective capsules were seen around the
      implants. CONCLUSION: At the end of the study, according to the FDI and ISO-7405
      standards, Targis and Artglass indicated biocompatibility with the subcutaneous
      connective tissue of the rat.

PMID- 21187622
TI  - Comparative efficacy of two treatment modalities for dentinal hypersensitivity: a
      clinical trial.
AB  - BACKGROUND: Dentin hypersensitivity is a recurrent condition causing discomfort
      and sometimes pain to the patient, which also deters him from maintaining
      adequate oral hygiene. Home care and office measures are used for treatment of
      this malady. AIM: To evaluate and compare the efficacy of 2 treatment modalities
      for dentinal hypersensitivity, iontophoresis with acidulated phosphate gel (APF)
      gel, and dentin-bonding agent application. MATERIALS AND METHODS: This split
      mouth randomized clinical study recruited subjects with a history of
      hypersensitivity with at least 2 teeth, verified by a light stroke with a dental
      explorer along the cervical third of the teeth. The patients were subjected to a
      1-s air blast and cold water stimuli and their responses were recorded on a
      verbal rating scale. A total of 30 sites from 15 patients were divided into Group
      A-1.23% APF gel iontophoresis; and Group B-aqueous solution of hydroxyl-ethyl
      methacrylate and glutaraldehyde. The teeth were evaluated immediately after the
      treatment and at the end of 2 weeks. In case of failure, the tooth was retreated
      with the same agent as before. RESULTS: The results were statistically analyzed
      using Kruskal-Wallis analysis of variance and Mann-Whitney U tests. There was no
      statistically significant difference between the groups at the end of 2 weeks.
      However, Group A was more effective clinically, with fewer number of failures
      compared with Group B. CONCLUSION: Both the agents showed a statistically
      significant reduction in sensitivity compared with baseline; however, APF gel
      iontophoresis was more effective in reducing hypersensitivity over a longer time
      period.

PMID- 21187623
TI  - Prevalence of hypodontia in nine- to fourteen-year-old children who attended the
      Mashhad School of Dentistry.
AB  - CONTEXT: Hypodontia is defined as the congenital absence of one or a few teeth,
      and is also the most common anomaly in dental development. This condition occurs
      either individually or as part of the symptoms of a syndrome, and it is more
      common in permanent teeth than in deciduous teeth, reporting a prevalence of
      between 1.6 and 9.6%. AIMS: The objective of this study is to investigate the
      prevalence of hypodontia for permanent teeth in nine- to 14-year-old children who
      attended the Mashhad School of Dentistry in 2007. SETTING AND DESIGN: We
      conducted this descriptive, analytical, cross-sectional study, to determine the
      mentioned aims. MATERIALS AND METHODS: In this descriptive, cross-sectional
      study, panoramic radiographs belonging to 600 children (351 girls and 249 boys),
      aged nine to 14 years, were available for examination. All related findings were
      recorded in the respective forms. STATISTICAL ANALYSIS USED: The data were
      processed using Exact and Chi-square tests. RESULTS: The prevalence of hypodontia
      in the girls was 9.2%, in the boys 8.8%, and in both sexes combined 9%. The most
      and the least frequent cases of absent teeth were the mandibular second premolars
      and the maxillary central incisor (only one child), respectively. The most
      commonly absent teeth were the mandibular second premolars, the maxillary lateral
      incisors, the mandibular central incisor, and the maxillary second premolars, in
      that order. CONCLUSIONS: This study showed a high frequency of hypodontia among
      the understudied population. Thus, due to the complicated treatment, accurate
      examination of children for on-time diagnosis of this developmental anomaly is
      crucial.

PMID- 21187624
TI  - Evaluation of the antibacterial and physical properties of glass ionomer cements
      containing chlorhexidine and cetrimide: an in-vitro study.
AB  - BACKGROUND: Incorporation of antibacterial agents frequently results in changes
      in the physical properties of restorative materials. MATERIALS AND METHODS: This
      in-vitro study investigated the antibacterial and physical properties of Glass
      ionomer cement (GIC) with chlorhexidine and cetrimide, to determine the optimal
      concentration, for incorporation of these agents to obtain antibacterial GICs for
      use with the Atraumatic restorative treatment approach. This was assessed using
      the agar diffusion test. Chlorhexidine diacetate and cetrimide were added to
      Glass ionomer cement type-IX (GIC-FUJI IX) at 1 and 2% W/W ratio. The
      experimental GIC specimens were placed on agar plates inoculated with
      Lactobacillus casei, and the area of inhibition was calculated after 48 hours.
      RESULTS: All the experimental GICs exhibited inhibition of bacteria, but the
      sizes were dependent on the concentration of the antibacterial agent.
      Incorporation of chlorhexidine diacetate and cetrimide, at 2%, significantly
      decreased the compressive strength, and the setting time was extended a little by
      the addition of any concentration of chlorhexidine and cetrimide. CONCLUSIONS:
      The present study demonstrated that experimental GICs containing chlorhexidine
      diacetate and cetrimide were effective in inhibiting bacteria associated with
      caries, and incorporation of 1% cetrimide was optimal to give the appropriate
      antibacterial and physical properties.

PMID- 21187626
TI  - Needs and demands of prosthetic treatment among two groups of individuals.
AB  - OBJECTIVES: The level of knowledge, awareness, and attitude about teeth
      replacement options among a group of medical and paramedical subjects and to
      compare them with the general population. MATERIALS AND METHODS: A self
      administered questionnaires using simple Arabic language were distributed to two
      groups of subjects. Questions focused on the willingness to replace the missing
      teeth, the preferable methods of choice for replacement, and the reasons for
      these choices. The first group (G-I) was from the medical and paramedical staff
      who work in a military hospital at Jordan Royal medical services, the dental
      staff was excluded from the study. The other group (G-II) was from the general
      population who attended the dental department in the same hospital with
      comparable level of education. All the participants were partially edentulous
      excluding the third molars. Clinical examination was done by qualified
      prosthodontist to evaluate the possible prosthetic treatment options for
      replacement. A total of 612 questionnaires were distributed, of which 533
      questionnaires were returned (response rate 87.09%). The results were analyzed
      and comparison was made between the two groups. RESULTS: Responses to questions
      about awareness and attitude about prosthetic management of missing teeth
      revealed that G-I have more awareness than G-II to the probable causes for
      tooth/teeth replacement and limitation of the preferable method for replacement
      (P<0.05). More than 80% of the participants believed that replacement of anterior
      teeth is more important than the posterior teeth. Implants and fixed partial
      denture (FPD), respectively, were more preferable than removable prosthesis,
      although clinically was not indicated in cases (P<0.05). There was no clinical
      benefit from replacement of missing teeth in 33.4% while only 6% believe this.
      CONCLUSIONS: This study showed that the awareness and attitude between the
      medical and paramedical staff to prosthetic needs is better than between general
      populations. The demands for dental replacement by patients were significantly
      different when compared with the actual needs.

PMID- 21187625
TI  - Comparison of the regenerative potential of an allograft used alone and that in
      conjunction with an immunosuppressive drug in the treatment of human periodontal
      infrabony defects: a clinical and radiological study.
AB  - BACKGROUND: Experimentation confirmed the conclusion that bone allografts, like
      other tissue and organ allografts, are immunogenic. These immune responses cause
      resorption of allograft, thus lowering the bone formation capacity of the graft.
      An attempt has been made in this study to prevent immune reactions and achieve
      enhanced regeneration of allograft-demineralized freeze-dried bone matrix by
      incorporating it with an immunosuppressive drug Cyclosporine-A (CsA) in the
      treatment of human periodontal infrabony defects. MATERIALS AND METHODS: Fifteen
      patients showing clinical evidence of almost bilateral infrabony defects
      requiring bone grafting procedures were selected. In each patient, the infrabony
      defect of one side of the arch was designated as Group A (control site) and the
      infrabony defect of the contralateral side of the same arch was designated as
      Group B (test site). RESULTS: On comparative evaluation of the two groups (by
      Student t-test), the mean values of reduction in probing depth (P=0.81 NS ) and
      gain in clinical attachment level (P=1.00 NS ) of Group B were found to be
      greater than that of Group-A, but the differences were statistically non
      significant. The mean linear bone fill (P=0.010 FNx08 ) of Group B was also
      detected to be higher than that of Group A, and the difference was found to be
      statistically significant. CONCLUSION: Increase in linear bone fill in Group B
      signifies the role of CsA in augmenting the regenerative potential of allograft
      by eliminating immune reactions.

PMID- 21187627
TI  - Genetic polymorphisms in periodontal diseases: an overview.
AB  - Periodontitis is a multi-factorial disease; several risk and susceptibility
      factors are proposed in its natural history. Genetics is considered a
      susceptibility factor in relation to periodontitis. This article is a
      nonsystematic review of literature and focuses on the role of genetic
      polymorphisms in periodontal diseases.

PMID- 21187628
TI  - Hyaluronic acid: a promising mediator for periodontal regeneration.
AB  - Hyaluronic acid (HA) is a natural-non sulphated high molecular weight
      glycosaminoglycan that forms a critical component of the extracellular matrix and
      contributes significantly to tissue hydrodynamics, cell migration and
      proliferation. The use of HA in the treatment of inflammatory process is
      established in medical areas such as orthopedics, dermatology and ophthalmology.
      In the field of dentistry, hyaluronate has shown anti-inflammatory, antiedematous
      and anti-bacterial effects for the treatment of gingivitis and periodontitis. Due
      to its potential role in modulation of wound healing, its administration to
      periodontal wound sites could achieve comparable beneficial effects in
      periodontal tissue regeneration and periodontal disease treatment.

PMID- 21187629
TI  - Endo-perio lesions: diagnosis and clinical considerations.
AB  - The interrelationship between periodontal and endodontic disease has aroused
      confusion, queries and controversy. Differentiating between periodontal and
      endodontic problems can be difficult. A symptomatic tooth may have pain of
      periodontal and/or pulpal origin. The nature of that pain is often the first clue
      in determining the etiology of such a problem. Radiographic and clinical
      evaluation can help clarify the nature of the problem. In some cases, the
      influence of pulpal pathology may create periodontal involvement. In others,
      periodontal pathology may create pulpal pathology. This review article discusses
      the various clinical aspects to be considered for accurately diagnosing and
      treating endo-perio lesions.

PMID- 21187630
TI  - Mongrelised genetics of H1N1 virus: a bird's eyeview.
AB  - H1N1 influenza, also known as "novel H1N1 virus" has led to a "global outcry."
      This virus is more virulent when compared with other seasonal flu viruses.
      Virulence may change as the adaptive mutation gene increases within the virus. A
      study at the US Centre for Disease Control and Prevention published in May 2009
      found that children had no preexisting immunity to the new strain as they showed
      no cross-reactive antibody reaction when compared with adults aged 18-64 years,
      who showed a cross-reactive antibody reaction of 6-9% and older adults with 33%
      immunity. This review article depicts H1N1 virus, its virulence with genetic
      evolution potential and preventive protocol for the dental professionals. This
      would allow us to comprehend the changes in the disease process and contribute in
      its prevention as "prevention is better than cure."

PMID- 21187631
TI  - Arsenic content in Portland cement: a literature review.
AB  - Portland cement (PC) is a hydraulic binding material widely used in the building
      industry. The main interest in its use in dentistry is focused on a possible
      alternative to mineral trioxide aggregate (MTA) because PC is less expensive and
      is widely available. In dentistry, PC has been used in dental procedures such as
      pulpotomy, pulp capping, repair of root perforation and root-end filling. The
      purpose of this article is review the dental literature about the PC, its
      composition with special attention to arsenic content, properties, and
      application in dentistry. A bibliographic research was performed in Bireme,
      PubMed, LILACS and Scopus data bases looking for national and international
      studies about the PC composition, properties and clinical use. It was observed
      that PC has favorable biological properties very similar to those of MTA. The PC
      has shown good cell proliferation induction with formation of a monolayer cell,
      satisfactory inflammatory response, inhibitory effect of prostaglandin and
      antimicrobial effect. Studies have shown that PC is not cytotoxic, stimulates the
      apposition of reparative dentin and permits cellular attachment and growth.
      Regarding arsenic presence, its levels and release are low. PC has physical,
      chemical and biological properties similar to MTA. Arsenic levels and release are
      low, therefore, unable to cause toxic effects.

PMID- 21187632
TI  - Restoration of posterior teeth using occlusal matrix technique.
AB  - This article describes a technique for duplicating occlusal surface anatomy using
      the Biteperf device. Duplication requires an intact occlusal enamel surface and
      is only indicated when caries lesions are hidden. The occlusal matrix technique
      allows for preservation of all anatomic details. When the last layer of composite
      has been placed, the occlusal matrix is forced into the uncured composite to
      replicate the original occlusal surface, instead of performing manual curing and
      shaping as in the standard approach. It is technically possible to achieve this
      effect with any material that is able to copy anatomic details. The main benefits
      of the occlusal matrix technique, more precisely the Biteperf, are the technical
      ease of use due to its simplicity and its high accuracy in reconstructing
      occlusal morphology.

PMID- 21187633
TI  - Collarless metal ceramic restorations to obscure the umbrella effect.
AB  - Esthetics with porcelain fused to metal restoration in the anterior region can be
      adversely affected due to the inadequate teeth preparations and design of the
      prosthesis. We presented here a case report where esthetics was compromised due
      to darkening of the interdental papilla and marginal gingival and overcontoured
      restorations in relation to porcelain fused to metal restorations. Good esthetic
      results were obtained by using basic principles of tooth preparation and using
      collarless metal ceramic restorations.

PMID- 21187634
TI  - Radiographic follow-up evaluation of sinus augmentation with deproteinized bovine
      bone and implant installation after loading.
AB  - Computed tomography (CT) has been used in diagnosis and implant treatment, and CT
      can be used to assess the dimensional stability of graft materials after
      maxillary sinus augmentation. A 50-year-old male patient was treated for the
      simultaneous placement of implants with sinus augmentation and two post-operative
      CT scans were performed after the delivery of the prosthesis at 9 months and 15
      months after the operation. There were no significant changes in alveolar bone
      height and the buccal window seemed to show remodeling over time. The continuity
      of the defect and the cortication were apparent in the 15-month post-operative CT
      scan. Implants installed simultaneously with sinus augmentation were well in
      function and the graft material seemed to be stable in maintaining tissue
      dimensions after the loading of the implants. The presented results need to be
      validated in further large case series or case-controlled studies.

PMID- 21187635
TI  - Recurrent chronic suppurative osteomyelitis of the mandible.
AB  - Osteomyelitis of the maxillofacial skeleton is a rare condition in recent times.
      The combination of antibiotic therapy and surgical debridement is effective in
      the treatment of chronic suppurative osteomyelitis (CSO). This case report
      describes the successful surgical treatment of CSO of the mandible in an 18-year
      old adult. Treatment included a pre-surgical course of antibiotics followed by
      sequestrectomy, resection of the coronoid process and removal of the
      pathologically fractured condylar process of the left side of the mandible. On
      post-operative clinical review at 1 week, the extra oral draining sinus healed
      with improved mouth opening.

PMID- 21187636
TI  - Central mucoepidermoid carcinoma of the mandible.
AB  - Central mucoepidermoid carcinoma are extremely rare tumors, representing about 2
      to 4% of all mucoepidermoid carcinomas. They are histologically low-grade
      cancers, usually affecting the mandible as uni- or multilocular radiographic
      lesions. Effective surgical treatment involving wide local excision or en bloc
      resection, allows patients to have a favorable prognosis after a long-term follow
      up. We report a case of central mucoepidermoid carcinoma affecting the mandible
      and discuss its clinical, radiographic, and histological findings, with a review
      of the literature.

PMID- 21187637
TI  - Autosomal-dominant osteopetrosis: an incidental finding.
AB  - Osteopetrosis is a descriptive term that refers to a group of rare, heritable
      disorders of the skeleton. Osteopetrotic conditions vary greatly in their
      presentation and severity, from just as an incidental finding on radiographs to
      causing life-threatening complications such as bone marrow suppression. It is
      caused by failure of osteoclast development and function. Osteopetrosis can be
      inherited as autosomal-recessive, autosomal-dominant or as X-linked traits, with
      the most severe forms being the autosomal-recessive ones. The severity of the
      disease is mild to moderate in the autosomal-dominant forms, with normal life
      expectancy. Diagnosis is largely based on clinical and radiographic evaluation.
      The present paper reports a case of autosomal-dominant osteopetrosis complicated
      by osteomyelitis with a short review of the condition.

PMID- 21187638
TI  - A simplified approach to fabrication of an ocular prosthesis: a case series.
AB  - The eye is a vital organ and an important component of facial expression. Loss of
      an eye has a crippling effect on the psychology of the patient. Enucleation of
      the eye is therefore normally followed by fabrication of an ocular prosthesis to
      improve esthetics. A less complex technique for fabrication of an ocular
      prosthesis is described in this report of two different cases.

PMID- 21187641
TI  - Announcement from the Editor-in-Chief regarding duplicate publication.
      Retraction.

PMID- 21187639
TI  - Ameloblastic fibro-odontoma of the anterior mandible in a 22-month-old boy.
AB  - We report an ameloblastic fibro-odontoma (AFO) presenting in the anterior
      mandible as a "bump on his gums" in a 22-month-old boy. An occlusal radiograph
      revealed a well-circumscribed radiolucency with scattered radiopaque foci. The
      tumor was enucleated under general anesthesia. The histologic findings were
      characteristic of an AFO, a mixed odontogenic tumor most common in the posterior
      jaws, primarily affecting individuals with an average age of 10 years. The
      clinical presentation, microscopic findings, differential diagnoses, and
      treatment are discussed.

PMID- 21187642
TI  - Detection of D-ornithine extracellularly produced by Corynebacterium glutamicum
      ATCC 13032::argF.
AB  - We found that Corynebacterium glutamicum ATCC 13032::argF extracellularly
      produced a large amount of D-ornithine when cultivated in a CGXII medium
      containing 1 mM L-arginine. This is the first report that C. glutamicum ATCC
      13032 or its mutant produces a D-amino acid extracellularly. C. glutamicum ATCC
      13032::argF produced 13 mM D-ornithine in 45 h of cultivation.

PMID- 21187643
TI  - Effects of a vitamin D analog, alfacalcidol, on bone and skeletal muscle in
      glucocorticoid-treated rats.
AB  - Glucocorticoids cause secondary osteoporosis and myopathy. The efficacy of
      vitamin D on osteoporotic fractures is thought to be through direct effects on
      bone and indirect effects on muscles that help to prevent falls. However, effects
      of vitamin D on muscles under glucocorticoid treatment remain unclear. Six-month
      old female Wistar rats were randomized to four groups: vehicle-treated controls;
      a prednisolone (PSL)-administered group (PSL group); an alfacalcidol-administered
      group (D group); and a group administered both PSL and alfacalcidol (PSL+D
      group). After a 4-week treatment period, maximum contractile strength and
      strength decrement index (SDI), an indicator of muscle fatigue, were measured in
      the calf muscle by electrical stimulation of the sciatic nerve. Cross-sectional
      area (CSA) of muscle fibers in the tibialis anterior muscle and bone mineral
      density (BMD) of the femur were evaluated. The PSL group showed significantly
      lower muscle strength, BMD and CSA of muscle fibers, and significantly higher SDI
      compared to the other three groups (P < 0.05). No significant differences were
      observed in any of these parameters among control, D, and PSL+D groups. These
      results suggest that in glucocorticoid-treated rats, alfacalcidol preserved not
      only BMD, but also muscle strength and muscle volume, and prevented muscle
      fatigue.

PMID- 21187644
TI  - Estrogen receptor alpha and beta are both involved in the cerebral VEGF/Akt/NO
      pathway and cerebral angiogenesis in female mice.
AB  - We have previously demonstrated that vascular endothelial growth factor (VEGF) is
      critical for cerebral angiogenesis in middle-aged female rats and may play a role
      in the flow-preserving neuroprotective actions of estrogen through its angiogenic
      and antiapoptotic properties. Here, we attempt to elucidate the effects of
      estrogen and the specific estrogen receptor (ER) subtype in cerebral VEGF/Akt/NO
      pathways and cerebral angiogenesis using 15-week old female mice that are either
      wild-type (WT), lack estrogen receptor alpha (ERalphaKO) or beta (ERbetaKO).
      Protein levels of VEGF and basic signaling molecules of VEGF angiogenic pathway
      in the frontal cortex were expressed as follows, as revealed by ELISA and
      immunoblotting : a) VEGF; WT: ERalphaKO: ERbetaKO, 47 +/- 15: 27 +/- 5: 28 +/- 5
      pg/mg, respectively (P < 0.01); b) KDR decreased about 40% in both ERalphaKO and
      ERbetaKO compared to WT; c) Akt was significantly down-regulated in both
      ERalphaKO and ERbetaKO compared to WT; d) phosphorylated Akt (pAkt); WT:
      ERalphaKO: ERbetaKO, 0.6 +/- 0.2: 0.3 +/- 0.01: 0.3 +/- 0.1 units/mg,
      respectively; e) phosphorylated eNOS significantly decreased about 45% in both
      ERalphaKO and ERbetaKO compared to WT. Cerebral capillary density decreased in
      both ERalphaKO and ERbetaKO compared to WT. Thus, it can be concluded that in
      female mice, VEGF/Akt/eNOS pathway plays an important role in cerebral
      angiogenesis and that both ER subtypes are involved in the regulation of VEGF and
      its signaling molecule expression in the frontal cortex.

PMID- 21187645
TI  - Fast-twitch muscle hypertrophy partly induces lipid accumulation inhibition with
      Alaska pollack protein intake in rats.
AB  - Fish protein is a source of animal protein that is consumed worldwide. Although
      it has been reported that the intake of Alaska pollack protein (APP) reduces
      serum triglyceride and body fat accumulation in rats, the mechanisms underlying
      these effects are poorly understood. In the present study, we fed 5-week-old male
      Sprague-Dawley rats a high-fat diet with APP or casein for 4 weeks. We
      reconfirmed that the intake of APP decreases serum triglycerides and inhibits
      visceral body fat accumulation in rats. We found that APP had a higher non
      digestive protein content than casein, and the amount of protein in feces was
      higher in the APP group than in the casein group. However, the amount of total
      lipids in feces did not differ significantly between the groups. We also found
      that the gastrocnemius muscle, a fast-twitch muscle, tended to increase in
      weight, and that the epididymal fat weight correlated negatively with
      gastrocnemius muscle weight in the APP group. These results imply that the
      enhancement of basal energy expenditure by fast-twitch muscle hypertrophy, rather
      than the enhancement of lipid excretion via feces, partly causes APP-induced
      inhibition of lipid accumulation in rats.

PMID- 21187646
TI  - Glial cell line-derived neurotrophic factor (GDNF) enhances sympathetic neurite
      growth in rat hearts at early developmental stages.
AB  - Molecular signaling of sympathetic innervation of myocardium is an unresolved
      issue. The purpose of this study was to investigate the effect of neurotrophic
      factors on sympathetic neurite growth towards cardiomyocytes. Cardiomyocytes
      (CMs) and sympathetic neurons (SNs) were isolated from neonatal rat hearts and
      superior cervical ganglia, and were co-cultured, either in a random or localized
      way. Neurite growth from SNs toward CMs was assessed by immunohistochemistry for
      neurofilament M and alpha-actinin in response to neurotrophic factors-nerve
      growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line
      derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF) and a
      chemical repellent, semaphorin 3A. As a result, GDNF as well as NGF and BDNF
      stimulated neurite growth. GDNF enhanced neurite outgrowth even under the NGF
      depleted culture condition, excluding an indirect effect of GDNF via NGF.
      Quantification of mRNA and protein by real-time PCR and immunohistochemistry at
      different developmental stages revealed that GDNF is abundantly expressed in the
      hearts of embryos and neonates, but not in adult hearts. GDNF plays an important
      role in inducing cardiac sympathetic innervation at the early developmental
      stages. A possible role in (re)innervation of injured or transplanted or cultured
      and transplanted myocardium may deserve investigation.

PMID- 21187647
TI  - The decreases of nephrin and nuclear WT1 in podocytes may cause albuminuria
      during the experimental sepsis in mice.
AB  - Sepsis is induced by infectious challenges, and septic organ failure often occurs
      under local and systemic inflammation. Albuminuria is also evident during sepsis,
      but little is known about the molecular basis of septic albuminuria. Using
      lipopolysaccharide (LPS)-treated mice as a sepsis model, we found that the loss
      of nephrin, a key component for maintaining podocyte slit diaphragm, became
      evident in accordance with the onset of albuminuria, especially 36 h post-LPS
      challenge (i.e., albumiuric stage). Likewise, nephrin mRNA levels were decreased
      to 13% of saline-treated mice. Such a transcriptional suppression of nephrin was
      associated with the loss of nucleus-localized Wilms tumor-1 (WT1), a
      transcriptional factor for up-regulating nephrin gene. Thereafter, urinary
      albumin levels were decreased in mice between 72 and 96 h post-LPS challenge
      (i.e., recovery-stage). Notably, nuclear localization of WT1 seemed to be
      normalized, and nephrin mRNA and protein levels returned near the basal level 72
      h post-LPS challenge. During LPS-mediated sepsis, there was a transient increase
      in blood interleukin-1beta, a suppressor of nephrin production in podocytes.
      Therefore, down-regulation of nephrin by the loss in nuclear WT1, along with
      hyper-cytokinemia, may underlie the mechanisms by which albuminuria is induced by
      infectious stresses.

PMID- 21187648
TI  - Effect of HSP47 expression levels on heterotrimer formation among type IV
      collagen alpha3, alpha4 and alpha5 chains.
AB  - We previously established stable transformants of the human embryonic kidney 293
      (HEK293) cell line that express type IV collagen alpha3, alpha4 and wild-type or
      mutant-type alpha5 chains. Using these cell lines, we confirmed that these three
      chains form a heterotrimer and that alpha5 chains containing mutations seen in
      Alport syndrome are defective in heterotrimerization. In these studies, the
      amount of heterotrimer that formed was much less than expected relative to the
      amount of alpha(IV) chains expressed. The aim of the present study was to
      determine the effect of the collagen-specific molecular chaperone heat shock
      protein 47 (HSP47), whose expression is low in HEK293 cells, on the
      heterotrimerization of alpha3(IV), alpha4(IV) and alpha5(IV) chains. Reduction of
      HSP47 levels by siRNA resulted in defects of heterotrimerization among the three
      chains, indicating that HSP47 plays a critical role in the heterotrimerization.
      On the other hand, overexpression of HSP47 did not influence heterotrimerization.
      Since many enzymes and molecular chaperons assist correct folding and
      trimerization of collagens, one or more enzymes and/or molecular chaperones,
      other than HSP47, might be deficient in HEK293 cells. Overexpression of HSP47
      decreased the secretion of heterotrimers containing the mutant alpha5(IV) chain,
      suggesting that HSP47 overexpression might enhance the quality control mechanisms
      of collagen synthesis by inhibiting the secretion of incorrectly structured
      heterotrimers.

PMID- 21187649
TI  - 2-Decenoic acid ethyl ester possesses neurotrophin-like activities to facilitate
      intracellular signals and increase synapse-specific proteins in neurons cultured
      from embryonic rat brain.
AB  - We presently found that medium-chain fatty acids (MCFAs) with 8-12 carbons and
      their esters facilitated activation (phosphorylation) of mitogen-activated
      protein kinases (MAPK)/extracellular signal-regulated kinases (ERK) 1/2 of
      cultured embryonic cortical/hippocampal neurons. In particular, trans-2-decenoic
      acid ethyl ester (DAEE) had the most potent activity. Additionally, DAEE
      activated phosphatidylinositol 3-kinase and cAMP-response element binding protein
      (CREB), suggesting that DAEE generates similar intracellular signal as
      neurotrophins. Therefore, details of the signal elicited by DAEE were examined in
      comparison with those of a neurotrophin, brain-derived neurotrophic factor
      (BDNF). We found that 1) DAEE phosphorylated MAPK/ERK1/2 via MEK activation
      without the involvement of tyrosine kinases of neurotrophin Trk receptors; 2)
      DAEE activated CREB predominantly through MAPK/ERK1/2 activation, not through
      other pathways such as cAMP/protein kinase A; and 3) DAEE increased the
      expression of RNAs of BDNF and neurotrophin-3 and the protein content of synapse
      specific proteins such as synaptophysin, synapsin-1, and syntaxin. Based on these
      observations we propose that DAEE and some other derivatives of MCFAs having
      neurotrophin-like neurotrophic activities may become therapeutic tools for
      certain neurological or psychiatric disorders.

PMID- 21187650
TI  - Gene expression profiles of the three major salivary glands in rats.
AB  - The protein components of saliva reflect the condition of the whole body as well
      as the salivary glands. The aim of this study is to characterize the gene
      expression profiles in each of the rat major salivary glands-the parotid,
      submandibular, and sublingual glands. Gene expression was analyzed using DNA
      microarrays, and observed differences in expression of representative genes were
      confirmed by quantitative, real-time polymerase chain reaction. Among the glands,
      the contribution to the high expression of genes encoding various proteins,
      specifically mucin 10, proline-rich glycoproteins, proline-rich protein 2,
      proline-rich proteoglycans, cystatin 10, amylase, deoxyribonuclease I, and von
      Ebner's gland protein, was significantly greater in the parotid gland than the
      other glands. The submandibular and sublingual glands had similar gene expression
      profiles that differed from profile of the parotid gland. For example, the genes
      encoding mucin 19 and ovomacroglobulin were highly expressed only in the
      submandibular and sublingual glands. In summary, we characterized gene expression
      in the rat major salivary glands and provided basic information on salivary gland
      marker proteins.

PMID- 21187651
TI  - Mutant p53 R248Q but not R248W enhances in vitro invasiveness of human lung
      cancer NCI-H1299 cells.
AB  - More than half of all human cancers are associated with mutations of the TP53
      gene. In regard to the functional interaction with the remaining wild-type (WT)
      p53 allele, p53 mutations are classified into two types, recessive and dominant
      negative (DN) mutations. The latter mutant protein has a DN activity over the
      remaining WT allele. We previously showed that the DN p53 mutant was useful as a
      predictor of poor outcome or a risk factor for metastatic recurrence in patients
      with some types of cancers, regardless of the presence or absence of loss of
      heterozygosity (LOH) of WT p53, suggesting that the DN p53 had 'gain-of-function
      (GOF)' activity besides the transdominance function. In this study, we
      investigated GOF activity of two DN p53 mutants which had a point mutation at
      codon 248 (R248Q and R248W), one of the hot spots, by transfecting them
      respectively into H1299 cells which originally expressed no p53 protein. Growth
      activity of the transfectants with the two mutants was not different from that of
      parent or Mock transfectants. Meanwhile, in vitro invasions of Matrigel and type
      I collagen gel by R248Q-transfectants were significantly higher than those by
      R248W-transfectants or the control cells. However, there were no differences in
      cell motile activities, expressions of extracellular matrix-degradative enzymes
      such as matrix metalloproteinases, urokinase-type plasminogen activator and
      heparanase, and their inhibitors, between R248Q- and R248W-transfectants. These
      findings indicate that the p53 mutants have a different quality in GOF activities
      even if the mutations occurred at the same codon. And detailed information of the
      status of p53, including transdominancy and GOF activity, is expected to be
      useful for diagnosis and therapeutic strategy fitting the individual patients.

PMID- 21187652
TI  - OSU-03012, a novel celecoxib derivative, induces cell swelling and shortens
      action potential duration in mouse ventricular cells.
AB  - OSU03012, a novel celecoxib derivative, has been shown to inhibit proliferation
      and induce apoptosis in numerous cancer cell lines. However, not much is known
      about its influence on cell volume regulation and cardiac function in the
      mammalian heart. We examined the effects of OSU-03012 on cell volume and action
      potentials in mouse ventricular cells. Video image analysis showed that cell
      volume increased on application of OSU-03012 in a dose-dependent manner. The
      action potential duration (APD) at 50% and 90% repolarization (APD(50) and
      APD(90) respectively) as well as the resting membrane potential (RMP) were
      measured in current-clamp experiments. OSU-03012 had little effect on APD(50) and
      RMP but induced approximately 30% shortening of APD(90). These results for cell
      volume and AP are similar to those in cells under ischaemia/hypoxia, and we
      confirmed that the shortening of APD(90) was almost completely recovered by
      glibenclamide, a potent inhibitor of ATP-sensitive potassium channels.We
      concluded that OSU-03012 may lead to cell swelling and shortening of AP via
      reduced ATP production in mouse ventricular cells.

PMID- 21187653
TI  - High QRS score on admission strongly predicts impaired myocardial reperfusion in
      patients with a first anterior acute myocardial infarction.
AB  - BACKGROUND: In patients with acute myocardial infarction (AMI), QRS score at
      presentation electrocardiogram (ECG) may reflect the evolutionary stage of the
      infarction and allow one to predict the degree of myocardial reperfusion
      potentially achievable by reperfusion therapy. METHODS AND RESULTS: The
      relationship between QRS score on admission ECG and myocardial blush grade, an
      angiographic marker of myocardial reperfusion, was examined in 416 patients with
      a first anterior AMI who received reperfusion therapy within 6h after symptom
      onset. Patients were classified into 3 groups according to QRS score: 0 or 1
      (n=102), 2-4 (n=228), and >=5 (n=86). Higher QRS scores were associated with a
      longer time to admission, a greater ST-segment elevation, a higher frequency of
      impaired initial and final culprit coronary vessel flow, a higher peak creatine
      kinase level, and a higher frequency of impaired myocardial reperfusion as
      defined by myocardial blush grade 0/1 on the final angiogram. Multivariate
      analysis showed that a high QRS score >=5 was the strongest predictor of impaired
      myocardial reperfusion (odds ratio 20.3, P<0.001). These findings were similar
      when the data were stratified according to time to admission (<=2h, >2h).
      CONCLUSIONS: In patients with a first anterior AMI treated by reperfusion
      therapy, admission high QRS score >=5 strongly predicts impaired myocardial
      reperfusion, even when presentation is early (<=2h).

PMID- 21187654
TI  - Lesion formation by ventricular septal ablation with irrigated electrodes:
      comparison of bipolar and sequential unipolar ablation.
AB  - BACKGROUND: Ablation of ventricular tachycardia originating from the
      interventricular septum (IVS) is often limited by the presence of re-entrant
      pathways deep in the IVS. We compared the efficacy of bipolar ablation vs.
      sequential unipolar ablation in creating a transmural lesion across the porcine
      IVS. METHODS AND RESULTS: Seventeen excised swine hearts were superfused by
      pulsatile saline flow. Bipolar ablation (at 30 W, 50 W or 70 W for 120 s) was
      performed between 2 saline-irrigated (20 ml/min) 4-mm tip electrodes, 1 on the
      left and 1 on the right side of the IVS. Sequential unipolar ablation (at 30 W,
      50 W or 70 W for 120 s) was performed on the left and right sides of the IVS with
      an irrigated-tip catheter. Bipolar ablation produced a narrower, deeper lesion
      than did unipolar ablation. A transmural lesion was created by sequential
      unipolar ablation in 7.7%, 8.3% and 0% of tissue preparations and by bipolar
      ablation in 50.0%, 46.7% and 71.4% of tissue preparations at 30 W, 50 W and 70 W.
      CONCLUSIONS: Bipolar ablation of the IVS was highly effective for creating a
      transmural IVS lesion.

PMID- 21187655
TI  - Frequency and location of yellow and disrupted coronary plaques in patients as
      detected by angioscopy.
AB  - BACKGROUND: Clarification of frequency and distribution of yellow plaques and
      disrupted plaques will increase understanding of acute coronary syndrome (ACS)
      onset. METHODS AND RESULTS: Consecutive patients with ACS (n=75) or without ACS
      (n=90) who received coronary angioscopic examination were studied. Distance from
      ostium to yellow plaques, diameter stenosis and vessel wall irregularity at the
      site of yellow plaques, their yellow color grade (grade 13) and if they had
      thrombus were analyzed. Yellow plaques with thrombus were regarded as disrupted.
      Average number of yellow plaques, grade-3 yellow plaques and disrupted yellow
      plaques per vessel was 4.0, 0.87 and 1.0, respectively. The number of grade-3
      yellow plaques and disrupted yellow plaques per vessel were larger in ACS than in
      non-ACS patients. Yellow plaques were distributed diffusely in the right coronary
      artery but more in mid-segments in the left anterior descending coronary artery
      and left circumflex coronary artery. Diameter stenosis in the non-culprit
      segments was severer at disrupted than at non-disrupted yellow plaques. Vessel
      wall irregularity was detected more frequently at disrupted than at non-disrupted
      yellow plaques. CONCLUSIONS: Approximately 4 yellow plaques, 1 grade-3 yellow
      plaque and 1 disrupted yellow plaque were detected per vessel. About 25% of
      detected yellow plaques were disrupted. More grade-3 yellow plaques and disrupted
      yellow plaques were detected in ACS than in non-ACS patients. These findings
      strengthen the association between yellow plaques detected by angioscopy and ACS
      events.

PMID- 21187656
TI  - N-acetylcysteine suppresses the progression of ventricular remodeling in acute
      myocarditis: studies in an experimental autoimmune myocarditis (EAM) model.
AB  - BACKGROUND: Electrical and structural remodeling, characterized by prolonged
      action potential duration (APD), Kv4.2 downregulation and cellular infiltration
      were studied in rat experimental autoimmune myocarditis (EAM). Because the
      reactive oxygen species (ROS) has been speculated to play a role in the promotion
      of such remodeling, the effect of N-acetylcysteine (NAC) on the progression of
      ventricular remodeling was evaluated. METHODS AND RESULTS: Six-week-old Lewis
      rats were immunized with porcine cardiac myosin. On Days 10-11 after the
      immunization, NAC (0, 1, 10, or 100mg) was injected intraperitoneally to EAM and
      control rats. On Day 14, the electrophysiological parameters were evaluated and
      the expression levels of the mRNA were examined by quantitative real-time reverse
      transcription polymerase chain reaction (RT-PCR).The EAM rats exhibited a typical
      acute myocarditis with prolonged APD and reduced Kv4.2 expression as previously
      reported. The myocarditis and electrical changes were significantly suppressed by
      NAC-treatment in a dose-dependent manner (P<0.05). In rats with 100mg NAC, the
      myocarditis was almost totally negated although the mortality increased. In rats
      with 1mg NAC, the suppression of myocarditis was not obvious, but APD
      prolongation and Kv4.2 reduction was attenuated (P<0.05). CONCLUSIONS: The NAC
      treatment suppressed ventricular remodeling in the EAM rats. This may indicate
      the role of oxidative stress in causing remodeling and myocarditis itself in the
      acute phase of myocarditis.

PMID- 21187657
TI  - Acute and chronic effects of smoking on arterial stiffness.
AB  - BACKGROUND: The brachial-ankle pulse wave velocity (baPWV) and cardio-ankle
      vascular index (CAVI) are used to evaluate arterial distensibility. The purpose
      of this study was to elucidate the acute and chronic effects of smoking on
      arterial stiffness as measured by baPWV and CAVI. METHODS AND RESULTS:  Ten male
      smokers were studied to evaluate the acute effect of smoking on arterial
      stiffness. To elucidate the chronic effect of smoking on arterial stiffness, 160
      male active smokers were analyzed. CAVI and baPWV were calculated by measuring
      the pulse volume record, blood pressure (BP), and vascular length from heart to
      ankle. CAVI and baPWV were measured using a VaSera VS-1000. In the acute study,
      baPWV and CAVI increased immediately after smoking 1 cigarette. In the chronic
      study, baPWV and CAVI significantly correlated with mean BP (MBP) and the
      Brinkman index. In multiple regression analysis, baPWV independently correlated
      with MBP, and CAVI independently correlated with the Brinkman index, but not with
      MBP. Receiver-operating characteristics (ROC) curves of baPWV and CAVI to predict
      Brinkman index >=500 demonstrated that the area under the ROC curve of CAVI was
      higher than that of baPWV. CONCLUSIONS:  Smoking causes a significant increase in
      arterial stiffness as measured by baPWV and CAVI. CAVI correlated with the
      Brinkman index, which suggests that CAVI is a useful index of the degree of
      arterial stiffness caused by smoking.

PMID- 21187658
TI  - A Novel Descriptive, Intelligible and Ordered (DINO) classification of coronary
      bifurcation lesions. Review of current classifications.
AB  - BACKGROUND: Several classification systems for coronary artery bifurcation
      lesions (CABL) have been described in the literature, but despite the commendable
      effort to simplify a difficult subject in interventional cardiology, all of them
      have certain limitations and shortcomings. METHODS AND RESULTS: The proposed
      Descriptive, INtelligible and Ordered (DINO) is a new descriptive and clinically
      oriented system of classifying CABLs. This classification system takes into
      consideration more details of the side branch angulation relative to the main
      branch. It uses self-explanatory terms and mnemonic characters (acronyms related
      to the branches of the bifurcation and the shape of side branch angulation). The
      DINO classification describes the extent of CABL distribution and designates its
      localization at the bifurcation region. Moreover, systematized simple and easy to
      remember terms may form a relevant classification basis for multicenter and meta
      analysis investigations. CONCLUSIONS: The DINO is the first verbally anchored,
      all-inclusive classification system of CABLs. It describes precisely side branch
      angulation, using self-explanatory and instructive terms that describe both the
      extent of the lesion's distribution and its localization. The current coronary
      bifurcation lesion classifications are reviewed.

PMID- 21187659
TI  - Restrictive mitral annuloplasty for functional mitral regurgitation: acute
      hemodynamics and serial echocardiography.
AB  - BACKGROUND: Long-term effects of restrictive mitral annuloplasty (RMA),
      especially on hemodynamics and left ventricular (LV) function in patients with
      functional mitral regurgitation (MR), have not been fully investigated. METHODS
      AND RESULTS: From 1999 to 2008, 44 patients with refractory heart failure and
      functional MR underwent RMA with stringent downsizing of the mitral annulus.
      Serial echocardiography was performed to evaluate LV function (reverse
      remodeling), estimated systolic pulmonary artery pressure (PAP) and mitral valve
      geometry at baseline and at discharge, and annually thereafter. Cardiac
      catheterization was performed at baseline, and at discharge to evaluate acute
      hemodynamic change. There were 3 early deaths, and the 5-year survival rate was
      78 +/- 8%. In 41 survivors the clinical symptoms, stratified according to New
      York Heart Association class, significantly improved after surgery. Postoperative
      cardiac catheterization showed significant unloading for left ventricle, as well
      as improvement in LV systolic function. Serial echocardiography showed that
      improvements in LV function and systolic PAP were sustained in the majority of
      patients. Multivariate Cox regression analysis identified preoperative pulmonary
      hypertension (systolic PAP>60 mm Hg) as the significant predictor for
      postoperative adverse cardiac events. CONCLUSIONS: RMA for functional MR resulted
      in sustained improvement of hemodynamics and LV function over time. Additional
      studies are needed to define the negative impact of preoperative pulmonary
      hypertension in patients with this condition.

PMID- 21187662
TI  - Rab27a, actin and beta-cell endocytosis.
AB  - The output and time-course of insulin release from pancreatic beta-cells are
      elegantly controlled. The secretory process comprises pre-exocytotic stages,
      exocytosis and post-exocytotic stages. The small GTPase Rab27a is known to
      regulate pre-exocytotic stages that determine the size of the readily-releasable
      pool of insulin granules. GTP-Rab27a and its specific effectors are responsible
      for this process like other GTPases. Recently, we searched for Rab27a-interacting
      proteins and identified coronin 3. Unexpectedly, coronin 3 only bound GDP-Rab27a
      and this interaction regulated post-exocytotic stages via reorganization of the
      actin cytoskeleton. Since glucose converts Rab27a from the GTP- to GDP-bound
      form, we suggested that Rab27a plays a crucial role in stimulus-endocytosis
      coupling in pancreatic beta-cells, and that this is the key molecule for membrane
      recycling of insulin granules. In this review, we provide an overview of the
      roles of Rab27a and its GTP- and GDP-dependent effectors in the insulin secretory
      pathway of pancreatic beta-cells.

PMID- 21187663
TI  - Improvement of the developmental ability of nuclear transfer embryos by using
      blastomeres from in vitro fertilized embryos selected according to the early
      developmental stage and cell division status as donor cells in cattle.
AB  - This study was conducted to improve the developmental ability of nuclear transfer
      (NT) embryos by using blastomeres from in vitro fertilized (IVF) embryos with
      high quality as donor cells. The IVF embryos selected at the 2-cell stage at 24-h
      postinsemination (hpi) and again at the >=8-cell stage at 48 hpi (Selected-IVF
      embryos) showed the highest blastocyst formation rate among embryos. When
      blastomeres from the Selected-IVF-embryos (Selected-NT group) or Nonselected-IVF
      embryos (Non-selected-NT group) were used as donor cells for NT, the blastocyst
      formation rate in the Selected-NT group (25.6%) was significantly higher than
      that in the Non-selected-NT group (13.5%). When blastomeres from the Selected-IVF
      embryos at 108 (contained many cells before cell division) and 126 hpi (contained
      many cells immediately after cell division) were used as donor cells for NT (108-
      and 126-NT groups, respectively), the 126-NT group showed a significantly higher
      blastocyst formation rate (32.1%) than the 108-NT group (16.8%). Embryo transfer
      of blastocysts in the 126-NT group showed that 11 of 23 recipients became
      pregnant; nine calves were obtained. For the NT embryos reconstructed using in
      vivo derived embryos, 9 of 20 recipients became pregnant; seven calves were
      obtained. These results indicate that the blastocyst formation rate of NT embryos
      can be improved by using blastomeres from IVF embryos selected at the early
      developmental stage, especially immediately after cell division, and that the
      resultant NT embryos have a high developmental ability to progress to term that
      is comparable to NT embryos reconstructed using in vivo derived embryos.

PMID- 21187664
TI  - Multi-institutional retrospective analysis of the inhomogeneity correction for
      radiation therapy of lung cancer.
AB  - The purpose of this work is to retrospectively analyze the effect of the
      inhomogeneity correction using clinically treated plan of stage III non-small
      cell lung cancer within multiple institutions in Japan. Twenty-five patients
      among five facilities of radiation therapy were registered for this study. The
      isocenter dose or D(95) of PTV or other important values were compared with and
      without an inhomogeneity correction using model-based algorithm. The differences
      in isocenter dose were 4% average and 10% maximum for the first Anterior
      Posterior opposed field plan to 40 Gy and 6% average and 11% maximum for the off
      cord boost oblique field plan of 20 Gy. The differences in D(95) dose were 1%
      average and 9% maximum for the first plan and 1% average and 6% maximum for the
      boost plan. D(95) prescription seemed to be a superior method; however, its
      reliability depends on each clinical case. Additionally, maximum dose, minimum
      dose and mean dose for both the primary tumor and the metastatic lymph node were
      analyzed, and the minimum dose had the most impressive results. In some cases,
      the target volume had unintended underdose of more than 10%. Finally, an analysis
      of the organ at risk was added, and this showed no meaningful differences for the
      V(20) of the lung and the maximum dose of the spinal cord. These results provide
      a standard for the effects of the inhomogeneity correction.

PMID- 21187665
TI  - Current concentration of artificial radionuclides and estimated radiation doses
      from 137Cs around the Chernobyl Nuclear Power Plant, the Semipalatinsk Nuclear
      Testing Site, and in Nagasaki.
AB  - To evaluate current environmental contamination and contributions from internal
      and external exposure due to the accident at the Chernobyl Nuclear Power Plant
      (CNPP) and nuclear tests at the Semipalatinsk Nuclear Testing Site (SNTS),
      concentrations of artificial radionuclides in edible mushrooms, soils and stones
      from each area were analyzed by gamma spectrometry. Annual effective doses were
      calculated for each area from the cesium contamination. Calculated internal
      effective doses of (137)Cs due to ingestion of mushrooms were 1.8 * 10(-1)
      mSv/year (y) in Gomel city (around CNPP), 1.7 * 10(-1) mSv/y in Korosten city
      (around CNPP), 2.8 * 10(-4) mSv/y in Semipalatinsk city, and 1.3 * 10(-4) mSv/y
      in Nagasaki. Calculated external effective doses of (137)Cs were 3.4 * 10(-2)
      mSv/y in Gomel city, 6.2 * 10(-2) mSv/y in Korosten city, 2.0 * 10(-4) mSv/y in
      Semipalatinsk city, and 1.3 * 10(-4) mSv/y in Nagasaki. Distribution of
      radionuclides in stones collected beside Lake Balapan (in SNTS) were (241)Am
      (49.4 +/- 1.4 Bq/kg), (137)Cs (406.3 +/- 1.7 Bq/kg), (58)Co (3.2 +/- 0.5 Bq/kg),
      and (60)Co (125.9 +/- 1.1 and 126.1 +/- 1.1 Bq/kg). The present study revealed
      that dose rates from internal and external exposure around CNPP were not
      sufficiently low and radiation exposure potency still exists even though current
      levels are below the public dose limit of 1 mSv/y (ICRP1991). Moreover, parts of
      the SNTS area may be still contaminated by artificial radionuclides derived from
      nuclear tests. Long-term follow-up of environmental monitoring around CNPP and
      SNTS, as well as evaluation of health effects in the population residing around
      these areas, may contribute to radiation safety with a reduction of unnecessary
      exposure of residents.

PMID- 21187666
TI  - Concurrent chemoradiotherapy with S-1 as first-line treatment for patients with
      oropharyngeal cancer.
AB  - PURPOSE: S-1 is an oral fluoropyrimidine. The purpose of this study was to review
      the clinical outcomes of S-1 with concurrent radiotherapy for patients with
      oropharyngeal cancer. MATERIALS AND METHODS: Between 2002 and 2007, 38 patients
      with oropharyngeal cancer treated concurrently with S-1 and definitive
      radiotherapy were reviewed. The clinical stage was Stage I in 4 patients, Stage
      II in 7, Stage III in 7, and Stage IV in 20. S-1 was administered orally twice
      daily for 4 consecutive weeks followed by a 2-week drug withdrawal. The initial
      dose of S-1 was 65 mg/m(2)/day. All patients were treated using three-dimensional
      conformal radiotherapy with a median total dose of 65.1 Gy (range, 60.0-71.0 Gy).
      Clinical outcomes and major acute toxicities were analyzed based on medical
      records and clinical follow-up. RESULTS: With a median follow-up time of 33
      months, the 3-year estimates of local-regional control, distant metastases-free
      survival, disease-free survival, and overall survival for all patients were 75%,
      80%, 65%, and 80%, respectively. The 3-year estimates of local-regional control
      according to stage were 100% for Stages I and II, 86% for Stage III, and 56% for
      Stage IV. The rate of >= Grade 3 acute mucositis was 32%, and the rate of >=
      Grade 3 hematological toxicities was 8%. No other severe toxicities were
      observed. CONCLUSIONS: Concurrent chemoradiotherapy with S-1 was found to be
      effective, especially for early disease. The treatment-related toxicities were
      acceptable, and the incidence of myelotoxicity was low. Further study must be
      carried out to compare with other chemotherapy regimens.

PMID- 21187667
TI  - Uptake of CDDP-containing polymeric micelles by cells using particle induced X
      ray emission.
AB  - Polymeric micelles loaded with cis-diamminedichloroplatinum(II), CDDP, (cisplatin
      micelles) enable higher accumulation in solid tumors and lower toxicities
      compared with CDDP alone. The combined use of cisplatin micelles with radiation
      is expected to enhance therapeutic effects and reduce side effects. The kinetics
      of cisplatin micelle uptake, however, have not been fully understood. Particle
      Induced X-Ray Emission has been employed in this study to measure the time
      transients of platinum in Chinese Hamster ovary cells. The results show that the
      platinum content of cells treated with cisplatin micelles increased more slowly
      than with CDDP alone, suggesting that cellular uptake could be controlled using
      micelles. The CDDP released from micelles was predominantly incorporated into the
      cells by diffusion. The uptake characteristics were further analyzed using
      micelles with different collapse rates. The results and techniques used in this
      study will be useful for designing an optimum treatment plan combining platinum
      containing polymeric micelles and radiation in clinical applications.

PMID- 21187668
TI  - Size, concentration and incubation time dependence of gold nanoparticle uptake
      into pancreas cancer cells and its future application to X-Ray Drug Delivery
      System.
AB  - One of the restrictions in the potential use of gold markers for medical
      imaging/tracking of harder tumors is its size. We propose to use gold
      nanoparticles which, due to its small size, can be administered conveniently via
      intravenous injection. One of the factors that determine the clinical utility of
      nanoparticles is the ability to enter cells. In this report, the stability of
      gold nanoparticles mixed with different media was determined by UV-vis
      spectroscopy. Gold nanoparticle size was confirmed by TEM. Intracellular uptake
      using different gold nanoparticle sizes, incubation times and concentrations were
      analyzed using Atomic Absorption Spectrometry (AAS). Temperature dependence
      uptake was also measured using AAS. The results showed that pancreas cancer cells
      uptake 20 nm gold nanoparticles preferentially compared to other gold
      nanoparticle sizes. Efficient accumulation of gold nanoparticles into pancreas
      cancer cells can be achieved at longer incubation time and higher concentration.
      The findings of this study will help in the design and optimization of the gold
      nanoparticle-based agents for therapeutic and diagnostic applications of X-ray
      Drug Delivery System.

PMID- 21187669
TI  - Impact of incomplete plan to treatment results of concurrent weekly cisplatin and
      radiotherapy in locally advanced cervical cancer.
AB  - To evaluate the efficacy of incomplete treatment protocols of cisplatin in
      concurrent chemoradiation for locally advanced cervical carcinoma. This
      retrospective study was performed in 165 consecutively treated patients with
      locally advanced cervical cancer who received a weekly cisplatin regimen. The
      number of weekly cisplatin cycles of each patient was recorded and used to
      discriminate between patients. Local control, disease free survival, distant
      metastasis-free survival, and toxicities were calculated using the software
      package SPSS version 15.0. Ninety-two patients (55%) completed the planned
      protocol of six cycles of weekly cisplatin. With the median follow-up time of
      38.2 months, the 3-year local control rate differed significantly in the two
      patient groups (95.4% of 6 cycles versus 84.8% of < 6 cycles; p = 0.028). No
      statistical significance was observed for disease-free survival (74.6% versus
      74.5%; p = 0.22) and distant metastasis-free survival (76.5% vs. 75.7%; p =
      0.88). In conclusion, the plan completion of concurrent cisplatin with
      radiotherapy was responsible for better local control. However, differences in
      disease-free survival and distant metastasis-free survival were not statistical
      significant.

PMID- 21187670
TI  - Effect of sunitinib combined with ionizing radiation on endothelial cells.
AB  - The aims of present study were to evaluate the efficacy of combining sunitinib
      with ionizing radiation (IR) on endothelial cells in vitro and in vivo. Human
      umbilical vein endothelial cells (HUVECs) were exposed to IR with or without
      sunitinib pretreatment. Apoptosis assay and cell cycle distribution were analyzed
      by flow cytometry. Clonogenic survival assay at 3 Gy dose with or without
      sunitinib was performed. The activity of phosphatidylinositol 3-kinase (PI3K)/Akt
      signal pathway was detected by Western immunoblot. Lewis lung carcinoma mouse
      model was built to examine the effect of combination therapy on endothelial cells
      in vivo. Microvasculature changes were detected by immunohistochemistry using
      anti-CD31 antibody. Our results showed combination therapy of sunitinib and IR
      significantly increased apoptosis of endothelial cells and inhibited colony
      formation compared to sunitinib or radiotherapy alone. It also resulted in cell
      cycle redistribution (decreasing cells in S phase and increasing cells in G2/M
      phase). The activity of PI3K/Akt signal pathway was inhibited, which could be the
      potential mechanisms that account for the enhanced radiation response induced by
      sunitinib. In vivo analysis showed that combination therapy significantly
      decreased microvasculature formation. The results demonstrated that combination
      therapy of sunitinib and IR has the potential to increase the cytotoxic effects
      on endothelial cells.

PMID- 21187671
TI  - Involvement of multiple PKC isoforms in phorbol 12,13-dibutyrate-induced
      contraction during high K(+) depolarization in bronchial smooth muscle of mice.
AB  - In airway smooth muscle, protein kinase C (PKC) has been implicated in a number
      of functional responses including the regulation of contractility. However, the
      exact role of PKC on bronchial smooth muscle (BSM) contraction is still unclear.
      In the present study, to determine the role of PKC activation in the BSM
      contraction, the effects of phorbol 12,13-dibutyrate (PDBu, a direct PKC
      activator) on BSM tone were examined in the absence and presence of K(+)-induced
      depolarization stimulation. The force development was not evoked by treatment
      with 1 uM PDBu alone. However, a strong contraction was induced by PDBu during
      high K(+) contraction. The contraction induced by PDBu during high K(+)
      stimulation was significantly abolished by pretreatment with nicardipine, an L
      type voltage dependent Ca(2+) channel blocker. In RT-PCR analysis, mRNAs of
      PKCalpha, beta, gamma, delta, epsilon, eta and theta isoforms were detected in
      mouse BSM. Go6976 (an inhibitor of PKCs alpha and beta) and rottlerin (an
      inhibitor of PKCdelta) significantly but partially inhibited the PDBu-induced BSM
      contraction during K(+) stimulation. GF109203X (an inhibitor of PKCs alpha, beta,
      gamma, and epsilon) completely inhibited the PDBu-induced contraction during K(+)
      stimulation. In conclusion, it is suggested that the PDBu-induced BSM contraction
      is dependent on an increase in cytosolic Ca(2+). Furthermore, it is possible that
      both cPKC and nPKC(s) participate in the PDBu-induced contraction of mouse BSM
      during K(+) stimulation.

PMID- 21187672
TI  - Local differences in electrogastrographic indices associated with total
      gastrectomy, total colectomy, distal gastrectomy and colonic replacement.
AB  - The electrogastrographic indices of spectral frequency, instability factor (IF),
      power amplitude, and power content (%) were compared between control subjects
      (C), and subjects following either total gastrectomy (TG), total colectomy (TC),
      distal gastrectomy (DG) or colonic replacement surgery (CR). In the fasting
      state, both the spectral frequency and IF of the epigastric 3-cycle per minute
      (cpm) group of the TC subjects were significantly lower than those indices in C,
      TG, DG, and CR subjects. In contrast, the power amplitude and power content of
      the epigastric 3-cpm group of both TG and DG subjects were significantly lower
      than those of C and TC subjects. The original epigastric waves of TG had
      remarkably high amplitudes. Furthermore, the absolute power of the epigastric 3
      cpm of the TC subjects was 10 times higher than that in either the C or TG
      subjects. These results may be partially explained by the assumption that the
      recorded epigastric electrogastrography (EGG) is mainly contributed to by the 3
      cpm myoelectric activity of the stomach and colon, while the infraumbilical EGG
      is mainly contributed to by the 3-cpm myoelectric activity of the colon.
      Topographic EGG maps visually supported these assumptions.

PMID- 21187673
TI  - Simple and non-invasive assessment of the accommodation reflex of the proximal
      stomach.
AB  - BACKGROUND: Impaired gastric accommodation of the proximal stomach is one of the
      major pathophysiological mechanisms in functional dyspepsia (FD). However, no
      useful method exists for the clinical evaluation of this phenomenon. AIM: The aim
      of the present study was to establish a simple and non-invasive method for
      evaluating the accommodation reflex of the proximal stomach. METHODS: Nine
      healthy subjects received up to 1,700 mL water (stepwise administration in 100-mL
      increments) using a nasogastric tube while they were in a supine position. To
      assess the meal-induced gastric accommodation reflex, we measured the cross
      sectional area of the proximal stomach via ultrasonography (US) at 3-min
      intervals after administration of water. We also measured the pressure of the
      water column using the same tube. Then, we administrated up to 400 mL of water in
      100-mL increments and measured the area of the proximal stomach in 44 FD patients
      with early satiation (the measurements were performed at intervals of 3-min), and
      we compared the results with those for 44 healthy subjects. RESULTS: The
      incremental changes in the area of the proximal stomach corresponded well with
      the amount of water administered. The area of the proximal stomach increased, but
      the antral area and the intragastric pressure remained relatively stable. After
      administration of more than 100 ml water, the area of the proximal stomach in
      healthy subjects was significantly greater than that in FD patients. CONCLUSION:
      US can be used to assess the isotonic expansion of the proximal stomach. We were
      able to distinguish FD patients with impaired accommodation reflex from healthy
      individuals by using this simple and easy method.

PMID- 21187674
TI  - Augmented PDBu-mediated contraction of bronchial smooth muscle of mice with
      antigen-induced airway hyperresponsiveness.
AB  - To explore the role of protein kinase C (PKC) in the augmented bronchial smooth
      muscle (BSM) contraction observed in the antigen-induced airway hyperresponsive
      (AHR) mice, the effects of a PKC activator, phorbol 12,13-dibutylate (PDBu), on
      BSM contraction were compared between the AHR and control mice. Actively
      sensitized mice were repeatedly challenged by antigen inhalation. Twenty-four
      hours after the final antigen challenge the isometrical contractions of the BSMs
      were measured. The BSM contraction induced by acetylcholine, but not high K(+)
      depolarization, was significantly augmented in the AHR mice. In BSMs of control
      mice, PDBu caused a significant increase in tension when the tissues were
      precontracted with high K(+), although PDBu itself had no effect on basal tone.
      The PDBu-mediated contraction was markedly augmented in BSMs of the AHR mice.
      These findings suggest that an increase in the PKC-mediated signaling is involved
      in the augmented contraction of BSMs in the antigen-induced AHR mice.

PMID- 21187675
TI  - Encapsulating peritoneal sclerosis associated with abnormal liver development in
      a young dog.
AB  - A 6-month-old male miniature pinscher dog developed chronic ascites, formation of
      fibrous membrane covering the abdominal organs, and numerous adhesions between
      the intestinal loops. The membrane and adhesions were surgically removed twice,
      but the dog died 1 month after initial presentation. Necropsy revealed recurrence
      of the membrane and intestinal adhesions. The fibrous membrane was composed of a
      thick layer of mature collagenous connective tissue, covered by immature
      collagenous connective tissue with mild lymphoplasmacytic infiltration, prominent
      neovascularization, and fibrin exudation. Similar fibrotic lesions were observed
      in the serosa of the liver, spleen, stomach and intestines. These findings are
      consistent with encapsulating peritoneal fibrosis reported in humans and dogs.
      The dog also had a maldeveloped liver, which is characterized by disorganized
      hepatic lobules and disarranged hepatic cords.

PMID- 21187676
TI  - Host cholesterol synthesis contributes to growth of intracellular Toxoplasma
      gondii in macrophages.
AB  - The intracellular protozoan Toxoplasma gondii lacks the ability to synthesize
      sterol and scavenges cholesterol from the low-density lipoprotein receptor (LDLR)
      pathway of its host to facilitate replication. Sterol biosynthesis inhibitors,
      however, have a demonstrated anti-Toxoplasma effect. In this study, we examined
      the host mevalonate pathway as a novel source of cholesterol for T. gondii and
      its effects on parasite growth in macrophages. Parasite growth did not
      significantly change in the absence of LDLR or when LDL was exogenously
      supplemented. Lovastatin and compactin, both inhibitors of hydroxymethylglutaryl
      CoA (HMG-CoA) reductase in the mevalonate pathway, significantly inhibited T.
      gondii growth in both wild-type and LDLR-knockout macrophages. Parasite growth
      was also suppressed by squalestatin, an inhibitor of squalene synthase, despite
      mevalonate producing isoprenoid intermediates in host cells. The present study
      demonstrates that lovastatin, compactin and squalestatin have anti-Toxoplasma
      activities and that the host cholesterol synthesis may contribute to parasite
      growth in macrophages.

PMID- 21187677
TI  - Extended exposure to trichostatin A after activation alters the expression of
      genes important for early development in nuclear transfer murine embryos.
AB  - The low viability of embryos reconstructed by somatic cell nuclear transfer
      (SCNT) is believed to be associated with epigenetic modification errors, and
      reduction of those errors may improve the viability of SCNT embryos. The present
      study shows the effect of trichostatin A (TSA), a strong inhibitor of histone
      deacetylase, on the development of murine SCNT embryos. After enucleation and
      nuclear injection, reconstructed murine oocytes were activated with or without
      TSA for 6 hr (TSA-6 hr). After activation, TSA treatment was extended to 3 hr
      (TSA-9 hr), 5 hr (TSA-11 hr) and 18 hr (TSA-24 hr) during culture. As a result,
      the SCNT embryos in the TSA-11 hr group showed a remarkably higher blastocyst
      rate (21.1%) when compared with the nontreated embryos (3.4%), while the
      concentration of TSA did not significantly affect embryonic development. The
      expressions of histone deacetylase (HDAC1 and HDAC2) and DNA methylation (DNMT3a
      and DNMT3b) genes decreased in the TSA-11 hr and TSA-24 hr groups, while there
      was an increase in the expression of histone acetyltransferase (P300 and CBP),
      pluripotency (OCT4 and NANOG) and embryonic growth/trophectoderm formation (FGF4)
      related genes in the same groups. The expression of CDX2, a critical gene for
      trophectoderm formation was upregulated only in the TSA-24 hr group. Our results
      show that TSA treatment during the peri- and postactivation period improves the
      development of reconstructed murine embryos, and this observation may be
      explained by enhanced epigenetic modification of somatic cells caused by TSA
      induced hyperacetylation, demethylation and upregulation of pluripotency and
      embryonic growth after SCNT.

PMID- 21187678
TI  - Molecular epidemiological survey of Theileria orientalis in Thua Thien Hue
      Province, Vietnam.
AB  - Theileria orientalis is a benign bovine protozoan parasite that occasionally
      causes serious economic loss in the livestock industry. We report the findings of
      a molecular epidemiological survey of T. orientalis in 94 Vietnamese yellow
      cattle, 43 water buffaloes, 21 sheep, 21 goats and 85 blood-sucking ticks of
      cattle in the Thua Thien Hue province of Vietnam. The major piroplasm surface
      protein (MPSP) gene of T. orientalis was detected using polymerase chain reaction
      from 13 cattle (13.8%), 11 water buffaloes (25.6%), 1 sheep (4.8%) and 9 ticks
      (10.6%). Phylogenetic analysis using MPSP gene sequences showed the presence of
      seven genotypes, four previously categorized genotypes (Types 1, 3, 5 and 7) and
      three new genotypes (Types N-1, N-2 and N-3).

PMID- 21187679
TI  - En block resection of a large hepatocellular carcinoma involving the caudal vena
      cava in a dog.
AB  - A 13-year-old neutered female Shih Tzu was referred for investigation of a
      cranial abdominal mass. Investigations including conventional radiography,
      abdominal ultrasonography and computed tomography confirmed the mass in the
      caudate lobe of the liver. As a collateral vein originating from the caudal vena
      cava (CVC) communicated with the azygos vein, the CVC was ligated and transected
      cranial to the right renal vein and cranial to the mass under temporary occlusion
      of the thoracic descending aorta and posthepatic CVC. The mass combined with the
      CVC was excised. The mass was confirmed as hepatocellular carcinoma (HCC). This
      report describes the first case with successful en bloc resection of a large HCC
      involving the CVC in a dog.

PMID- 21187680
TI  - Prevalence of murine norovirus infection in Korean laboratory animal facilities.
AB  - Currently, murine noroviruses (MNV) are the most prevalent viral pathogens
      identified in laboratory animal facilities. While several reports exist
      concerning the prevalence of MNV in North American research facilities, very few
      reports are available for other parts of the world, including Korea. This study
      evaluated the prevalence of MNV infection in 745 murine sera collected from 15
      animal facilities in Korea by enzyme linked immunosorbent assay (ELISA). Positive
      cases were subcategorized by murine strain/genetics, housing environments and
      animal sources. In summary, 6.6% of inbred/outbred mice purchased from commercial
      vendors were seropositive, 9.6% of in-house colonies were seropositive and 27.0%
      of genetically modified mice (GMM) were seropositive. Partial gene amplification
      of fecal isolates from infected animals showed that they were homologous (100%)
      with MNV-4.

PMID- 21187681
TI  - Development and application of West Nile virus subgenomic replicon RNA expressing
      secreted alkaline phosphatase.
AB  - We have developed a West Nile virus (WNV) subgenomic replicon harboring the
      secreted alkaline phosphatase (SEAP) reporter gene instead of viral structural
      genes (designated repWNV/SEAP). The repWNV/SEAP allowed easy evaluation of viral
      replication efficiency by direct measurement of SEAP secretion in the cell
      culture medium in physical containment level 2 facilities. Furthermore, we
      validated the availability of this system using a known anti-flavivirus gene,
      mouse oligoadenylate synthetase 1b (Oas1b). The Oas1b-transfected cells were more
      resistant to repWNV/SEAP replication than the original cells. Thus, this system
      not only affords a useful tool for identification/evaluation of anti-flavivirus
      genes/drugs in terms of safety, ease of use and reliability, but should be able
      to reduce or replace the bioassay using laboratory animals.

PMID- 21187682
TI  - Differential kinetic activities of glycerol kinase among African trypanosome
      species: phylogenetic and therapeutic implications.
AB  - African trypanosome species are causative agents for sleeping sickness in humans
      and nagana disease in cattle. Trypanosoma brucei can generate ATP via a reverse
      reaction with glycerol kinase (GK) when alternative oxidase (AOX) is inhibited;
      thus, GK is considered to be a crucial target for chemotherapy combined with AOX.
      However, the energy metabolism systems of African trypanosome species other than
      T. brucei are poorly understood. Thus, GK genes were surveyed from genome
      databases and cloned by PCR from T. vivax and T. congolense. Then, recombinant GK
      proteins (rGK) of T. vivax, T. congolense and T. brucei were expressed and
      purified. Kinetic analysis of these rGK proteins revealed that the K(m) values of
      T. congolense rGK for ADP and G-3-P substrates were lower than those of T. vivax
      and T. brucei. The expression level of GK molecules was highest in T. congolense
      cells and lowest in T. vivax cells. Based on these results, effective combination
      dosages of ascofuranone, a specific inhibitor of AOX, and glycerol, an inhibitor
      of the GK reverse reaction, were determined by using in vitro-cultured
      trypanosome cells.

PMID- 21187683
TI  - Development of correction formulas for canine and feline urine specific gravity
      measured using a Japanese refractometer.
AB  - One of the most important functions of the kidney is to concentrate urine through
      the reabsorption of water. Urine specific gravity (USG) is used in routine tests
      of urine concentration and can be estimated using a refractometer. However, as
      the scale of Japanese refractometer is based on experimental data from healthy
      Japanese people, and human USG obtained by Japanese refractometers show higher
      values than that by refractometer produced in Europe or the U.S.A. The purpose of
      this study was to establish correction formulas for the USG of dogs and cats
      measured using Japanese refractometers. In this study, we found that Japanese
      refractometers overestimated USG in both dogs and cats. This study shows that the
      correlation formulas described in this study are useful for the accurate
      evaluation of USG.

PMID- 21187684
TI  - Expression and characterization of bluetongue virus serotype 21 VP7 antigen: C
      terminal truncated protein has significantly reduced antigenicity.
AB  - In the present study, group-specific antigen VP7 of bluetongue virus (BTV)
      serotype 21 isolated from cattle in Tochigi prefecture in Japan in 1994 was
      characterized by sequencing and expression. Gene was amplified from cDNA
      synthesized on viral dsRNA using reverse-transcriptase-PCR. Nucleotide sequence
      of this isolate showed high similarity with other published BTV VP7 sequences.
      Full-length and C-terminal truncated forms of VP7 were expressed in insect cells
      by a baculovirus gene expression system under control of the viral polyhedrin
      promoter. Expression of full-length recombinant VP7 was confirmed by
      immunoprecipitation with VP7 specific monoclonal antibody (8A3B.6, ATCC).
      Recombinant proteins expressed with or without 6x His-tag showed good expression
      levels in TN5 cells and reacted well with the monoclonal antibody in the indirect
      ELISA. However C-terminal truncated VP7 with His-tag failed to react with this
      monoclonal antibody, while poor antigenicity was evident when it was reacted with
      infected bovine serum. Reduced antigenicity of the latter suggested that C
      terminal truncation affects 8A3B.6 epitope construction probably via inhibition
      of VP7 trimer structure formation.

PMID- 21187685
TI  - Clinical Application of MR Spectroscopy and Imaging of Brain Tumor.
AB  - Advanced imaging techniques, including diffusion tensor imaging (DTI), perfusion
      weighted imaging (PWI), and magnetic resonance spectroscopy (MRS) can provide
      more information than that regarding anatomy. These techniques have been commonly
      used in the clinical field and recently been shown useful in diagnosing brain
      tumors, especially in cases difficult to specify using conventional imaging.
      Differentiation requires more than attention to each advanced image. Diagnostic
      accuracy improves by combining information from MRS with that from other
      sequences, such as maps of apparent diffusion coefficient (ADC) and fractional
      anisotropy (FA) generated from DTI and of cerebral blood volume (CBV) generated
      from PWI. We show clinical applications of advanced imaging techniques, combined
      MRS, for brain tumor.

PMID- 21187686
TI  - High Resolution Three-dimensional T(2)*-weighted Imaging at 3T: Findings of
      Cerebellopontine Angle Schwannomas and Meningiomas.

PMID- 21187687
TI  - Effects of strenuous exercise with eccentric muscle contraction: physiological
      and functional aspects of human skeletal muscle.
AB  - PURPOSE: we used magnetic resonance (MR) imaging and ultrasonography in
      combination with a dynamometer to assess physiological and functional aspects of
      the skeletal muscles after strenuous exercise that included eccentric
      contraction. METHODS: seven male subjects (mean age, 21.7 years) performed ankle
      plantar flexion that included eccentric contraction and underwent diffusion
      weighted MR imaging for calculation of the apparent diffusion coefficient (ADC)
      of the triceps surae muscles. We used ultrasonography combined with a dynamometer
      to measure the displacement of the myotendinous junction (MTJ) of the medial
      gastrocnemius and maximal isometric force during ankle plantar flexion. We also
      assessed the level of muscle soreness of the calf using a visual analogue scale.
      We measured these parameters before exercise and one, 2, 3, 5, and 8 days after
      exercise and examined significant changes from the pre-exercise value using
      repeated-measures analysis of variance with Dunnett's test for each measurement
      parameter. RESULTS: one day after exercise, we observed increased muscle soreness
      (P<0.001) and decreased MTJ displacement (P<0.05); isometric force generation
      tended to decrease, but the change was not significant. Muscle soreness peaked 2
      days after exercise (P<0.001) and remained significantly increased until 5 days
      after exercise (P<0.005). The medial gastrocnemius exhibited increased ADC value
      3 days after exercise (P<0.005), but the lateral gastrocnemius and the soleus
      showed no significant changes throughout this study. CONCLUSION: our findings
      suggest that muscle damage induced by eccentric contraction manifests as muscle
      soreness and dysfunction early after exercise and later increases water diffusion
      within damaged muscle.

PMID- 21187688
TI  - Using BOLD imaging to measure renal oxygenation dynamics in rats injected with
      diuretics.
AB  - PURPOSE: we used blood oxygenation level-dependent magnetic resonance imaging
      (BOLD MRI) to measure renal oxygenation dynamics in rats injected with diuretics
      and evaluated diuretic effect on renal oxygenation. METHODS: we performed BOLD
      MRI studies in 32 rats using a 1.5-tesla MR imaging system for animal
      experiments. We intravenously injected rats with saline (n=7), furosemide (n=7),
      acetazolamide (n=6), or mannitol (n=6). For controls, 6 rats were not injected
      with drugs. We estimated the apparent transverse relaxation rate (R(2)*) from the
      apparent transverse relaxation time (T(2)*)-weighted images and measured the time
      course of R(2)* at 4-min intervals over approximately 30 min. RESULTS: compared
      with preadministration values, the R(2)* value did not change significantly in
      either the cortex or medulla in the control and mannitol groups but decreased
      significantly in the saline group; the R(2)* value significantly decreased in the
      medulla but did not change significantly in the cortex in the furosemide group;
      and the R(2)* value significantly increased in the medulla and significantly
      decreased in the cortex in the acetazolamide group. CONCLUSION: our study results
      suggest that BOLD MRI is useful for evaluating the dynamics of renal oxygenation
      in response to various diuretics in the renal cortex and in the medulla.

PMID- 21187689
TI  - Biexponential Signal Attenuation Analysis of Diffusion-weighted Imaging of
      Breast.
AB  - PURPOSE: in vivo, the attenuation of diffusion-weighted imaging (DWI) signal at
      high b-values is sometimes nonlinear when plotted with semilogarithmic function
      and is fit well by a biexponential function. Previous reports have indicated that
      the fast and slow component fractions of the apparent diffusion coefficient (ADC)
      can be derived by biexponential fitting and that these fractions correspond to
      the actual diffusion components in the extra- and intracellular space. In this
      study, we investigated the clinical utility of DWI for the breast by performing
      DWI using multiple b-factors on healthy volunteers and clinical subjects,
      analyzing the signal by fitting it with a biexponential equation, and comparing
      the fitting parameters of breast lesions. PATIENTS AND METHODS: we investigated 8
      healthy women as normal cases and 80 female patients with a total of 100 breast
      tumors (42 benign, 58 malignant tumors) as clinical cases. We performed DWI using
      12 b-values for the healthy cases and 6 b-values for the clinical cases, up to a
      maximum b-value of 3500 s/mm(2). RESULTS: decay of DWI signal of normal mammary
      glands, most cysts, and some fibroadenomas showed a monoexponential relationship,
      and conversely, that of intraductal papilloma (IDP) and malignant tumors was well
      fitted by a biexponential function. Comparison of parameters derived from
      biexponential fitting demonstrated no significant difference between benign and
      malignant lesions. For malignant tumor subtype, the fast component fraction of
      noninvasive ductal carcinoma was statistically greater than that of invasive
      ductal carcinoma. CONCLUSIONS: although the parameters from biexponential fitting
      may reflect the character of tumor cellularity, because pathological diagnosis
      was performed with an emphasis on cell configuration or shape rather than
      cellularity, it was difficult to distinguish malignant from benign tumors,
      including many IDPs, or to distinguish tissue types using DWI signal attenuation
      alone.

PMID- 21187690
TI  - A simplified method of T(1)rho mapping in clinical assessment of knee joint.
AB  - PURPOSE: we assessed the clinical utility of our proposed simplified method for
      T(1)rho mapping calculations. MATERIALS AND METHODS: ten healthy subjects
      underwent scanning on a 3-tesla magnetic resonance system using an 8-channel
      phased-array coil. For each subject, we obtained sagittal T(1)rho-prepared images
      using 5 different time of spin-lock pulses (TSL=1, 20, 40, 60, and 80 ms),
      produced conventional T(1)rho maps (cT(1)rho maps) using all TSLs, and recomputed
      our proposed simplified T(1)rho maps (sT(1)rho maps) using a decreasing number of
      TSLs (from 4 to 2). We then investigated the differences and correlations in
      T(1)rho values of the tissues obtained using different numbers of spin-lock
      times. RESULTS: there was a strong positive correlation (single measure
      intraclass correlation coefficient=0.948; 95% confidence interval=0.911 to 0.970)
      in T(1)rho values of tissues between the cT(1)rho and sT(1)rho [1, 80] maps. The
      2 maps were comparable, though there was a small difference in T(1)rho value
      between the two. The total scan time to acquire the data from 5 spin-lock times
      was 16 min 15 s. Similarity of the T(1)rho [1, 80] map with the conventional
      approach reduced scan time by 60%, to 6 min 30 s. CONCLUSION: the clinical
      relevance of our proposed simplified method is potentially similar to that of the
      conventional method, and our method requires a shorter examination time and
      generally preserves the reliability of the T(1)rho relaxation time of the
      tissues.

PMID- 21187692
TI  - Solitary plasmacytoma of the sternum detected incidentally by MR imaging of the
      cervical spine.
AB  - We incidentally detected a case of solitary plasmacytoma of the sternum by
      magnetic resonance (MR) imaging of the cervical spine. At detection, the patient
      had no symptoms, the lesion was localized in the bone marrow of the sternum, and
      there were no findings of bone destruction. The lesion showed high contrast on
      diffusion-weighted images, gradually enlarged over 3 years, and was confirmed as
      a solitary plasmacytoma at open biopsy 3 years after detection. Radiologists
      should pay attention to incidental findings in the upper part of the sternum at
      MR imaging examination of the cervical spine.

PMID- 21187691
TI  - Diagnostic performance of ADC for Non-mass-like breast lesions on MR imaging.
AB  - We assessed the usefulness and limitations of utilizing apparent diffusion
      coefficient (ADC) values on diffusion-weighted imaging (DWI) for the differential
      diagnosis of benign and malignant non-mass-like breast lesions. We
      retrospectively reviewed 27 such lesions (16 malignant, 11 benign) detected on
      magnetic resonance (MR) imaging and analyzed the enhancing patterns of dynamic
      contrast-enhanced DCE-MRI (distribution and internal enhancement), kinetic curve
      patterns, and ADC values. All images were obtained with a 1.5-tesla MR unit, with
      patients supine. On DCE-MRI, malignant lesions tended to show either segmental or
      branching-ductal distribution, and when lesions with these patterns were
      considered malignant, sensitivity was 68.8%; specificity, 63.6%; positive
      predictive value (PPV), 73.3%; negative predictive value (NPV), 58.3%; and
      accuracy, 66.7%. Kinetic curve analysis did not reliably differentiate benign and
      malignant non-mass-like lesions. There was no significant difference between the
      mean ADC value of the malignant lesions, 0.968 * 10(-3) mm(2)/s at b=1000
      s/mm(2), and that of benign lesions, 1.207 * 10(-3) mm(2)/s (P=0.109). Receiver
      operating characteristic (ROC) analysis revealed the most effective threshold of
      ADC value for differentiating tumors as 1.1 * 10(-3) mm(2)/s; values lower than
      this were observed more often in malignant than benign lesions (P=0.054). Us of
      this threshold yielded sensitivity of 68.8%; specificity, 72.7%; PPV, 78.6%; NPV,
      61.5%; and accuracy, 70.4%. Combining the ADC value criteria with the analysis of
      DCE-MRI pattern increased sensitivity to 93.8%, negative predictive value (NPV)
      to 85.7%, and accuracy to 77.8% but decreased specificity to 54.5%. Use of ADC
      values does not adequately improve DCE-MRI performance for differential diagnosis
      of non-mass-like breast lesions, but adding the ADC value criteria to the DCE-MRI
      pattern analysis improves sensitivity, NPV, and accuracy.

PMID- 21187693
TI  - Spontaneously ruptured endometrioma associated with endometrioid adenocarcinoma:
      MR findings.
AB  - A 38-year-old woman was transferred to the hospital with lower abdominal pain.
      Magnetic resonance (MR) imaging revealed an irregular ovarian wall with a solid
      component and a fluid-fluid level in the cystic mass and the pelvic space, which
      was thought to be pathognomonic for the rupture of an endometrioma with a
      malignant ovarian tumor. Histologic examination following adnexectomy revealed a
      ruptured endometrioma associated with endometrioid adenocarcinoma. A fluid-fluid
      level in the cystic mass and pelvic space may be pathognomonic MRI feature for a
      rupture of either an endometrioma or an endometrioma with a malignant tumor.

PMID- 21187695
TI  - Detection of pulmonary embolism with 99mTc-labeled F(ab)2 fragment of anti-P
      selectin monoclonal antibody in dogs.
AB  - Pulmonary embolism is a common and potentially life-threatening condition, and
      its correct diagnosis is highly desirable before anticoagulant therapy is
      initiated. However, the safe and accurate diagnosis of acute pulmonary embolism
      remains a challenge. Single photon emission computed tomography (SPECT) is a
      highly sensitive scintigraphic imaging technique. Pulmonary embolism can be
      detected by SPECT with (99m)Tc-labeled imaging agents that bind to components
      present predominantly on thromboemboli. P-selectin is an adhesion glycoprotein
      that is expressed in platelets and endothelial cells. P-selectin on activated
      platelets is a suitable biomarker of the active thrombus process. The objective
      of this study was to evaluate (99m)Tc-labeled F(ab)(2) fragment of anti-P
      selectin monoclonal antibody SZ51, (99m)Tc-SZ51-F(ab)(2), for imaging pulmonary
      embolism in beagle canines. SZ51 was digested to F(ab)(2) fragment, named SZ51
      F(ab)(2), and its specific binding to P-selectin on either human or canine
      platelets was verified by flow cytometry assay. In each dog, an 18-gauge catheter
      was inserted into left or right pulmonary artery, and a two-stranded spiral
      stainless-steel coil (20 mm) was inserted through catheter. At 30 min after coil
      placement, X-ray angiography was performed to document the pulmonary embolism and
      the locations of the coil. After intravenous injection of (99m)Tc-SZ51-F(ab)(2),
      experimental thrombi in dogs could be consistently visualized for 2-3 hours by
      SPECT. Pulmonary embolism showed higher uptake of (99m)Tc-SZ51-F(ab)(2). The
      present study suggests that (99m)Tc-SZ51-F(ab)(2) may be a promising agent for
      detecting pulmonary embolism.

PMID- 21187694
TI  - Visualization of endolymphatic hydrops in Meniere's disease with single-dose
      intravenous gadolinium-based contrast media using heavily T(2)-weighted 3D-FLAIR.
AB  - Heavily T(2)-weighted 3-dimensional fluid-attenuated inversion recovery (hT(2)W
      3D-FLAIR) technique has been reported to be more sensitive than conventional 3D
      FLAIR in detecting low concentrations of gadolinium-based contrast media (GBCM)
      in fluid. We applied hT(2)W-3D-FLAIR to visualize endolymphatic hydrops of
      Meniere's disease in 3 patients 4 hours after single-dose intravenous injection
      of GBCM and successfully visualized endolymphatic hydrops in either the cochlea
      or vestibule in all patients. This technique can be implemented in a clinical
      setting.

PMID- 21187696
TI  - Surgical treatment is recommended for advanced oral squamous cell carcinoma.
AB  - Oral squamous cell carcinoma is one of the most frequent types of head and neck
      cancers in Japan. Although recent reports have shown positive results of non
      surgical treatment for advanced head and neck squamous cell carcinoma, including
      tongue cancer, no clear treatment strategies have been established for oral
      cancers, except for tongue cancer. To assess appropriate therapies, we conducted
      a retrospective chart review of 114 Japanese patients with oral cancers that were
      pathologically diagnosed as squamous cell carcinoma, excluding tongue cancers.
      The overall and the disease specific 5-year survival rates were 53% and 61%,
      respectively. Univariate and multivariate analyses revealed a lower stage (I, II,
      or III) and non-surgical treatment as good and poor prognostic factors of oral
      squamous cell carcinoma, respectively, based on their hazard ratios of 0.17 (95%
      CI 0.045-0.60, p = 0.0061) and 5.3 (95% CI 2.7-11, p < 0.0001). Furthermore,
      impact of surgery was well documented in the operable stage IVa cancers (p =
      0.00015). The surgical treatment consisted of the wide resection of the primary
      tumor and the neck dissection for stage III or IV tumors. The present data also
      suggest that adjunctive therapy, such as post-operative radiation therapy or post
      operative chemo-radiation therapy, shows no survival benefit compared to the
      surgery alone. We therefore recommend the surgical treatment for advanced oral
      squamous cell carcinoma in Japanese patients. These results would be helpful in
      future clinical trials, especially in non-surgical treatment studies of oral
      squamous cell carcinoma in Japan.

PMID- 21187697
TI  - Loss of anti-arrhythmic effect of vagal nerve stimulation on ischemia-induced
      ventricular tachyarrhythmia in aged rats.
AB  - Reduced vagal activity is associated with increased risk for life-threatening
      arrhythmia during myocardial ischemia (MI); conversely, the increase in vagal
      tone may provide protective effect against ventricular arrhythmias. In fact,
      vagal nerve stimulation (VNS) exerted an anti-arrhythmic effect by preserving
      connexin 43 (Cx43), a gap junction protein in ventricles, in a rat model of MI.
      We investigated the effects of VNS on ventricular tachyarrhythmia during acute MI
      and the expression of Cx43 in aged rats. Both adult (3-4 months) and aged (>= 24
      months) male rats were subjected to ischemia of 30 min. VNS was applied before
      ischemia either alone or in combination with atropine (0.5 mg/kg) or
      carbenoxolone, a gap junction inhibitor (10 mg/kg). During the 30-min ischemia,
      the incidence of ventricular tachycardia (VT) or ventricular fibrillation (VF)
      was higher in aged rats compared with adult rats. VNS significantly suppressed VT
      and VF in adult rats and these effects were eliminated by atropine or
      carbenoxolone. In contrast, VNS did not suppress VT and VF in the aged rats.
      Moreover, ischemia did not change the expression levels of total Cx43 protein in
      adult and aged rat ventricles. However, the expression level of total Cx43
      protein was two times lower in sham-operated aged rats than that in sham-operated
      adult rats. Thus, in aged rats, loss of anti-arrhythmic effect of VNS is
      associated with reduced expression of Cx43 protein. These findings suggest that
      Cx43 may be an important target for inhibiting ischemia-induced VT in adult
      patients but not in aged patients.

PMID- 21187698
TI  - Alcohol and aldehyde dehydrogenase polymorphisms and a new strategy for
      prevention and screening for cancer in the upper aerodigestive tract in East
      Asians.
AB  - The ethanol in alcoholic beverages and the acetaldehyde associated with alcohol
      consumption are Group 1 human carcinogens (WHO, International Agency for Research
      on Cancer). The combination of alcohol consumption, tobacco smoking, the inactive
      heterozygous aldehyde dehydrogenase-2 genotype (ALDH2*1/*2) and the less-active
      homozygous alcohol dehydrogenase-1B genotype (ADH1B*1/*1) increases the risk of
      squamous cell carcinoma (SCC) in the upper aerodigestive tract (UADT) in a
      multiplicative fashion in East Asians. In addition to being exposed to locally
      high levels of ethanol, the UADT is exposed to a very high concentration of
      acetaldehyde from a variety of sources, including that as an ingredient of
      alcoholic beverages per se and that found in tobacco smoke; acetaldehyde is also
      produced by salivary microorganisms and mucosal enzymes and is present as blood
      acetaldehyde. The inefficient degradation of acetaldehyde by weakly expressed
      ALDH2 in the UADT may be cri! tical to the local accumulation of acetaldehyde,
      especially in ALDH2*1/*2 carriers. ADH1B*1/*1 carriers tend to experience less
      intense alcohol flushing and are highly susceptible to heavy drinking and
      alcoholism. Heavy drinking by persons with the less-active ADH1B*1/*1 leads to
      longer exposure of the UADT to salivary ethanol and acetaldehyde. The ALDH2*1/*2
      genotype is a very strong predictor of synchronous and metachronous multiple SCCs
      in the UADT. High red cell mean corpuscular volume (MCV), esophageal dysplasia,
      and melanosis in the UADT, all of which are frequently found in ALDH2*1/*2
      drinkers, are useful for identifying high-risk individuals. We invented a simple
      flushing questionnaire that enables prediction of the ALDH2 phenotype. New health
      appraisal models that include ALDH2 genotype, the simple flushing questionnaire,
      or MCV are powerful tools for devising a new strategy for prevention and
      screening for UADT cancer in East Asians.

PMID- 21187699
TI  - Emergency medicine in Japan.
AB  - There have been few reports published in English on emergency medicine (EM) in
      Japan; the main reason for this is that the concept of EM was different in Japan
      from that in western countries. In the 1960s, legislation was passed in Japan
      that implemented emergency medical services, and emergency hospitals were
      designated by the government. There were no emergency medicine specialists, and
      so surgeons/physicians without specialist training in emergency medicine provided
      care to emergency patients (the multispecialist-type model). The Japanese
      Association for Acute Medicine (JAAM), an academic society for emergency
      physicians, was founded in 1973. In its pioneering days, this association focused
      mostly on trauma/burn care and also influenced policymaking. In 1977, the
      government built emergency medical service centers (the ICU-type model) and
      reorganized all emergency medical facilities into three levels. With the aging of
      society, the number of non-trauma patient! s presenting at hospitals, especially
      in the elderly population, has increased and has resulted in some cases of
      refusal by hospitals to accept emergency patients. A new postgraduate medical
      education curriculum was legislated in 2004 that mandated EM training for all
      postgraduates and encouraged reinforcement of emergency departments in teaching
      hospitals. The JAAM established a committee to promote the ER-type model of EM in
      2003. By 2007, more than 150 JAAM-affiliated hospitals had implemented this type
      of EM. In conclusion, emergency medicine in Japan is currently based on a mixture
      of three models: the multispecialist-type, the ICU-type and the ER-type models.

PMID- 21187700
TI  - Learning experiences and assessment in the first 2 years of the medical course at
      King's College London School of Medicine.
AB  - The medical curriculum at King's College London School of Medicine is a 5 year
      course; an extended program (6 years) and a graduate entry program (4 years) are
      also available. The first 2 years of the curriculum comprise phases 1 and 2. The
      curriculum consists of core material that is common to all students and student
      selected components (students undertake three such components in the first 2
      years). Phase 1 lasts 12 weeks and students learn the principles of tissue and
      organ structure and function. They are also introduced to the practice of
      medicine (concepts of health, communication, ethics, inter-professional education
      and medicine in the community). Phase 2 consists of 36 weekly clinical scenarios
      that place basic medical science in a clinical context. Phase 2 covers
      cardiovascular, respiratory, gastrointestinal, renal and musculoskeletal systems;
      nutrition; endocrinology; head and neck anatomy; neuroscience; genetics; and
      infections. Teaching continues in pri! mary care and in the hospitals and
      includes basic and advanced life support. Learning experiences include lectures,
      tutorials, practical classes, dissection and prosection, communication skills, e
      learning, student-led sessions and primary care and hospital visits. Assessment
      consists of in-course assessment (e.g., presentations, tests and essays) and end
      of-year examinations which consist of written papers and an objective structured
      clinical examination at the end of year 2. The main strengths of the program
      include the scenario format of learning and the practice of medicine early on.
      The difficulties arise mainly from the large numbers of students (420 per year).

PMID- 21187701
TI  - Association of Paraoxonase 1 (PON1) polymorphisms with osteoporotic fracture risk
      in postmenopausal Korean women.
AB  - There is increasing evidence of a biochemical link between lipid oxidation and
      bone metabolism. Paraoxonase 1 (PON1) prevents the oxidation of low-density
      lipoprotein (LDL) and metabolizes biologically active phospholipids in oxidized
      LDLs. Here, we performed association analyses of genetic variation in PON1 to
      ascertain its contribution to osteoporotic fractures (OFs) and bone mineral
      density (BMD). We directly sequenced the PON1 gene in 24 Korean individuals and
      identified 26 sequence variants. A large population of Korean postmenopausal
      women (n=1,329) was then genotyped for eight selected PON1 polymorphisms. BMD at
      the lumbar spine and femoral neck was measured using dual-energy X-ray
      absorptiometry. Lateral thoracolumbar (T4-L4) radiographs were obtained for
      vertebral fracture assessment, and the occurrence of non-vertebral fractures
      (i.e., wrist, hip, forearm, humerus, rib, and pelvis) was examined using self
      reported data. Multivariate analyses showed that none of the polymorphisms was
      associated with BMD at either site. However, +5989A>G and +26080T>C polymorphisms
      were significantly associated with non-vertebral and vertebral fractures,
      respectively, after adjustment for covariates. Specifically, the minor allele of
      +5989A>G exerted a highly protective effect against non-vertebral fractures
      (OR=0.59, P=0.036), whereas the minor allele of +26080T>C was associated with
      increased susceptibility to vertebral fractures (OR=1.73, P=0.020). When the risk
      for any OFs (i.e., vertebral or non-vertebral) was considered, the statistical
      significance of both polymorphisms persisted (P=0.002-0.010). These results
      suggest that PON1 polymorphisms could be one of useful genetic markers for OF
      risk in postmenopausal women.

PMID- 21187702
TI  - Therapeutic effects of recombinant Salmonella typhimurium harboring CCL22 miRNA
      on atopic dermatitis-like skin in mice.
AB  - Th-2-biased immune responses are known to play a key role in the pathogenesis of
      atopic dermatitis. In particular, the macrophage-derived chemokine CCL22 is
      directly implicated in Th-2-associated skin inflammatory reactions, and its
      levels are significantly elevated in serum and are correlated with disease
      severity in atopic dermatitis. In this study, we tested the development of
      genetic therapeutic options to treat atopic dermatitis using bacteria expressing
      miRNA. We constructed a recombinant strain of Salmonella typhimurium expressing
      CCL22 miRNA (ST-miRCCL22) for the in vivo knockdown of CCL22. The CCL22 gene was
      downregulated with CCL22 miRNA in activated lymphocytes. In mice with a cutaneous
      disease similar to atopic dermatitis, interleukin-4 was inhibited and interferon
      g was induced after treatments with ST-miRCCL22. Furthermore, CCL22 levels were
      suppressed in the atopic mice treated with ST-miRCCL22. These results suggest
      that ST-miRCCL22 may be an effective genetic agent for treating atopic
      dermatitis.

PMID- 21187703
TI  - [Retrospetive analysis of early postoperative complications of radical cystectomy
      and urinary diversion performed during a 17-year period].
AB  - We retrospectively analyzed early postoperative complications in 293 consecutive
      patients withbladder cancer who underwent radical cystectomy with urinary
      diversion from 1990 to 2007 at the Department of Urology of the Sapporo Medical
      University School of Medicine. The Common Terminology Criteria for Adverse Events
      (ver 3.0) was used to evaluate complications that occurred within 30 days after
      surgery, and grade 3 and higher grades according to the criteria were defined as
      complications in this study. The guidelines of the Centers for Disease Control
      and Prevention were used for the classification of surgical site infection. Early
      postoperative complications were found in 158 cases (54%). Acute pyelonephritis
      (APN), which was related to the removal of the ureteral catheter, was the most
      frequent complication, found in 96 (33%), followed by surgical site infection in
      39 (13%), and ileus in 33 (11%). When transient APN was excluded, the rate for
      complications was 30%. Possible life-threatening complications were experienced
      in 15 patients (5%) including 2 (0.7%) who eventually died of the complications.
      The preoperative grade 3 score of the American Society of Anesthesiologists (ASA
      score) was significantly related to development of early postoperative
      complications in univariate analysis. In multivariate analysis, a grade 3 ASA
      score and the estimated blood loss were independent factors to predict
      development of early complications. Postoperative nasogastric tubing was not
      related to ileus after surgery, suggesting that postoperative indwelling of the
      tube is not routinely needed. Although about half of the patients experienced
      early postoperative complications, they were usually transient and manageable.
      Thus, careful evaluation of the preoperative ASA score and a reduction in the
      amount of bleeding during surgery may lower the development of early
      postoperative complications.

PMID- 21187704
TI  - [Clinical study of penis-conserving treatment for carcinoma of penis].
AB  - We retrospectively reviewed 9 patients with squamous cell carcinoma of the penis
      who were treated with penis preservation between April 1988 and January 2008. Six
      patients had recurrence and 4 patients died of cancer. Patients treated with
      penis preservation had a significantly higher. Future studies are needed on a
      larger number of cases.

PMID- 21187705
TI  - [Neurotoxicity of valacyclovir in a peritoneal dialysis patient].
AB  - The patient was a 67-year-old man with a 2-year history of peritoneal dialysis
      for end-stage renal disease due to hypertensive nephropathy. He presented to a
      dermatologist with a complaint of pain in the right femoral region. He was
      diagnosed as having herpes zoster and valacyclovir, 1,000 mg/day, was prescribed.
      After 5 days of taking valacyclovir orally, he felt fretful and hallucinations
      appeared. He was admitted to our hospital and was hospitalized in our urology
      ward. We diagnosed his condition as neurotoxicity caused by an overdose of
      valacyclovir. As his general condition was stable, he was treated only by
      continuation of peritoneal dialysis. After 7 days of hospitalization, the
      neurotoxicity completely disappeared and he left the hospital. His serum
      acyclovir concentration at admission was 20.20 MUg/l, and was reduced to 0.7
      MUg/l when he left the hospital. This supported our diagnosis of valacyclovir
      induced neurotoxicity. In this case, valacyclovir should have been reduced to 500
      mg/day, considering his renal function. Although we could treat the patient only
      by continuation of peritoneal dialysis, hemodialysis seems to be an effective
      treatment method in the case of unstable general condition or severe adverse
      effects, because it can eliminate the serum acyclovir.

PMID- 21187706
TI  - [Ganglioneuroma with calcification mimicking adrenal tumor: a case report].
AB  - A 28-year-old woman was referred to our hospital complaining of upper abdominal
      discomfort. The patient had been receiving medical treatment for hypertension.
      Computed tomography revealed a 30 mm solid tumor with calcification in the left
      adrenal gland and a 8 mm nodule in the right adrenal gland. Endocrinological
      examinations revealed no activity of either adrenal mass. The left adrenal tumor
      was extirpated, because malignancy of the tumor was not ruled out.
      Histopathological examination proved that the tumor was ganglioneuroma arising
      from the extra-adrenal retroperitoneum.

PMID- 21187707
TI  - [Extra-adrenal pheochromocytoma with the manifestation of catecholamines
      cardiomyopathy: a case report].
AB  - A 22-year old female had an episode of acute heart and respiratory failure
      requiring mechanical ventilation ducing a trip overseas. Echocardiography
      demonstrated akinesis of the apical area (left ventricle ejectionfraction(LVEF)
      =15%). Since computed tomography (CT) with coronary angiography to rule out acute
      coronary syndrome showed no abnormalities, she was diagnosed with morphological
      stress cardiomyopathy due to akinesis of the apical area. After returning to
      Japan, she was admitted to our hospital for further examination. She had an
      increased level of catecholamines in 24-hour urine. 131Imetaiodobenzyguanidine
      scintigraphy, CT scan and fluorodexyglucose positron emission tomography revealed
      a retroperitoneal mass. From these results, a diagnosis of extra-adrenal
      pheochromocytoma with catecholamine-induced cardiomyopathy was made. Histological
      diagnosis of the laparoscopically resected tumor was pheochromocytoma. After the
      operation, the level of catecholamines in 24-hour urine was normalized.

PMID- 21187708
TI  - [Pancreatic metastasis from renal cell carcinoma 25 years after radical
      nephrectomy].
AB  - We report a case of pancreatic metastasis from renal cell carcinoma detected 25
      years after radical nephrectomy. A 74-year-old man, who had undergone radical
      nephrectomy for renal cell carcinoma at age 49, was found by computed tomography
      to have a strongly enhanced mass on the pancreatic head. The patient underwent
      pancreaticoduodenectomy and the pathological diagnosis was metastatic renal cell
      carcinoma. This was evidently a slow growing tumor because the metastatic
      pancreas tumor was well demarcated and the metastasis was found 25 years after
      the primary operation. Aggressive surgical treatment of isolated metastatic
      lesions offers a chance of long-term survival. Patients with a history of RCC
      should undergo a long-term follow-up to detect and evaluate metastasis to
      pancreas as well as other organs.

PMID- 21187709
TI  - [A case report of pyogenic spondylodiscitis mimicking spinal metastasis of
      urothelial carcinoma].
AB  - A 75-year-old man was admitted to our hospital with a complaint of fever and
      backpain. He was diagnosed with acute pyelonephritis, and was administered an
      antibiotic. However, since there was no improvement in the symptoms, he was
      admitted to our hospital. Computed tomography revealed a tumor which was in
      contact with a thoracic vertebra. Because he had had a total cystectomy for
      bladder cancer in the past, we suspected a spinal metastasis of urothelial
      carcinoma. However, after magnetic resonance imaging, we finally diagnosed it as
      pyogenic spondylodiscitis, and his condition improved after administration of
      antibiotics.

PMID- 21187710
TI  - [Spontaneous rupture of the ureter as the primary symptom of malignant lymphoma].
AB  - We report a rare case in which upper ureteral rupture was the primary symptom of
      malignant lymphoma. A 74-year-old female visited our hospital with left flank
      pain. Computed tomography showed urinoma around the left kidney and retrograde
      pyelography showed a diffuse filling defect in the left ureter and a rupture of
      the upper portion of that ureter. A urine cytology specimen from the left ureter
      was class V, suggesting undifferentiated carcinoma or malignant lymphoma. An open
      laparotomy revealed a nodule on the omentum and diffuse fibrosis around both
      ureters, and the histopathological diagnosis was diffuse large B-cell lymphoma.
      The patient' s ureteral stenosis disappeared after she received six cycles of R
      CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone and rituximab)
      chemotherapy. We should be aware that malignant lymphoma can be the cause of a
      spontaneous ureteral rupture.

PMID- 21187711
TI  - [A case of urinary incontinence due to hypoplastic kidney with an ectopic
      ureteral opening: successful treatment with transcatheter arterial embolization].
AB  - We report a 21-year-old woman,who presented with a major complaint of urinary
      incontinence without dry time. On the basis of computed tomographic examination
      and vaginography,she was diagnosed as having a hypoplastic left kidney with a
      solitary ectopic ureteral opening on the left. Transcatheter arterial
      embolization of the renal artery using anhydrous ethanol was conducted for renal
      ablation. No postoperative complications were noted,and the symptoms of urinary
      incontinence were eliminated. Embolization of the renal artery for ablation of a
      hypoplastic kidney with symptoms can be achieved without laparotomy while causing
      little stress and few complications,with an outcome comparable to surgical
      nephrectomy. This procedure is expected to be adopted as a standard therapeutic
      modality in the future.

PMID- 21187712
TI  - [A case of neobladder-cutaneo fistula after cystectomy].
AB  - A 69-year-old man was admitted for the treatment of muscle-invasive bladder
      carcinoma. Total cystectomy was performed and an ileal neobladder was constructed
      by a modification of Studer's method. However, a week later, a subcutaneous
      abscess occurred withwound dehiscence. Open drainage and wound debridement was
      carried out. Three weeks later, a neoblader-cutaneous fistula was seen on
      cystography. We managed it conservatively by means of wound debridement and
      washing with physiological saline. The fistula was closed on the 95th day after
      operation. The patient can now pass urine by himself.

PMID- 21187713
TI  - [A case report of transurethral resection of eroding urethral mesh after a
      tension-free vaginal tape procedure].
AB  - A 72-year-old woman presented with lower urinary tract symptoms (incomplete
      voiding, voiding pain, and gross hematuria) 2 years after a tension-free vaginal
      tape (TVT) procedure for stress urinary incontinence. Cystoscopy revealed erosion
      of the urethra associated with a urethral stone attached to a polypropylene mesh.
      We performed transurethral resection of the polypropylene mesh and transurethral
      lithotripsy. After removal of the mesh, she had stress urinary incontinence but
      her symptoms resolved. Urethral erosion is a rare complication of TVT, and the
      method of handling the intrusive mesh has not been standardized. Transurethral
      endoscopic resection of the eroding mesh is a minimally invasive and successful
      procedure that should be considered for the treatment of this complication
      resulting from TVT.

PMID- 21187714
TI  - [A case of cerebellar hemorrhage secondary to autonomic dysreflexia (AD) in a
      patient with cervical spinal cord injury].
AB  - The patient was a 72-year-old man with C4 incomplete tetraplegia incurred in a
      traffic accident in March, 2008. He managed his bladder with an indwelling Foley
      catheter. In August, 2009, the catheter obstruction induced autonomic dysreflexia
      (AD). Although distention of bladder disappeared immediately, cerebeller
      hemorrhage occurred due to AD. After an operation the patient was alive but left
      with disturbance of consciousness. AD is one of the most important complications
      of high-level spinal cord injury. The pathophysiology of AD is the disconnection
      of the spinal sympathetic centers from spuraspinal control, leading to unopposed,
      sustained sympathetic outflow below the spinal lesion. Clinically, it is
      characterized by an acute increase in blood pressure, headache, sweating, and
      facial flushing and is often triggered by nonspecific stimuli below the level of
      the spinal cord lesion. The main triggering factors are bladder overdistension
      and bowel distension. Most events subside after prompt recognition and removal of
      the triggering factors, but, it is a life threatening emergency that may lead to
      apoplexy. This life-threatening complication should be kept in mind in the
      patients with spinal cord injury.

PMID- 21187715
TI  - [false-positive results of human chorionic gonadotropin beta measurement after
      high orchiectomy for stage i seminoma: report of a case].
AB  - A 21-year-old male presented at our hospital with a complaint of left scrotal
      swelling. The serum human chorionic gonadotropin-beta (hCG-beta) level was 1.3
      ng/ml. A left high orchitectomy was performed, and a histological study
      demonstrated seminoma. Computerized tomography showed no evidence of metastasis.
      Adjuvant radiation therapy with 25 Gy was performed for stage I seminoma.
      Although complete clinical remission was achieved,the hCG-beta level remained
      slightly positive (0.3-0.5 ng/ml). The urine hCG-beta-core fragment was
      determined to be within normal limits. This confirmed that the result of serum
      hCG-beta measurement was false-positive in our case. The patient received no
      additional treatment, and is free from recurrence 3 years and 1 month after
      surgery. In the testicular germ cell tumors,the measurement of urine hCG-beta
      core fragment is useful for differential diagnosis in cases of low level-positive
      serum hCG-beta without clinical evidence of disease.

PMID- 21187716
TI  - Interactions of meniscal cells with extracellular matrix molecules: towards the
      generation of tissue engineered menisci.
AB  - Menisci are one of the most commonly injured parts of the knee. Conventional
      surgical interventions are often associated with a long-term increased risk of
      osteoarthritis. Meniscal tissue engineering utilizes natural or synthetic
      matrices as a scaffold to guide tissue repair or regeneration in three
      dimensions. Studies have shown that a diverse cellular response can be triggered
      depending on the composition of the surrounding extracellular matrix (ECM)
      components. As such, attempts have been made to replace or repair meniscus
      defects using tissue grafts or reconstituted ECM components prepared from a
      multitude of tissues. This commentary summarizes the most recent data on the
      response of meniscal cells to ECM components, both in vivo and in vitro, and
      focuses on their potential roles in meniscal repair and regeneration. We also
      discuss our recent investigations into the interactions of meniscal cells and a
      self assembled biomimetic surface composed of meniscal ECM molecules. The
      biological effects conferred by the biomimetic surface, in terms of cell
      adhesion, proliferation, gene expression profiles and matrix synthesis, were
      evaluated. Finally, some suggested directions for future research in this field
      are outlined.

PMID- 21187717
TI  - Cardioprotection through autophagy: ready for clinical trial?
AB  - Interventions that reduce infarct size in animal models have largely failed to
      improve outcome in patients suffering acute myocardial infarction (MI), or 'heart
      attack'. Our group recently reported a reduction of infarct size by
      chloramphenicol treatment in a porcine in vivo model of acute MI, through a
      mechanism involving the induction of autophagy. Since 2005 several studies have
      implicated autophagy as a target for cardioprotection.

PMID- 21187718
TI  - Autophagy regulates myeloid cell differentiation by p62/SQSTM1-mediated
      degradation of PML-RARalpha oncoprotein.
AB  - PML-RARalpha oncoprotein is a fusion protein of promyelocytic leukemia (PML) and
      the retinoic acid receptor-alpha (RARalpha) and causes acute promyelocytic
      leukemias (APL). A hallmark of all-trans retinoic acid (ATRA) responses in APL is
      PML-RARalpha degradation which promotes cell differentiation. Here, we
      demonstrated that autophagy is a crucial regulator of PML-RARalpha degradation.
      Inhibition of autophagy by short hairpin (sh) RNA that target essential autophagy
      genes such as Atg1, Atg5 and PI3KC3 and by autophagy inhibitors (e.g. 3
      methyladenine), blocked PML-RARalpha degradation and subsequently granulocytic
      differentiation of human myeloid leukemic cells. In contrast, rapamycin, the mTOR
      kinase inhibitor, enhanced autophagy and promoted ATRA-induced PML-RARalpha
      degradation and myeloid cell differentiation. Moreover, PML-RARalpha co
      immunoprecipitated with ubiquitin-binding adaptor protein p62/SQSTM1, which is
      degraded through autophagy. Furthermore, knockdown of p62/SQSTM1 inhibited ATRA
      induced PML-RARalpha degradation and myeloid cell differentiation. The
      identification of PML-RARalpha as a target of autophagy provides new insight into
      the mechanism of action of ATRA and its specificity for APL.

PMID- 21187719
TI  - Acute induction of autophagy as a novel strategy for cardioprotection: getting to
      the heart of the matter.
AB  - There is no question that necrosis and apoptosis contribute to cardiomyocyte
      death in the setting of myocardial ischemia-reperfusion. Indeed, considerable
      effort and resources have been invested in the development of novel therapies
      aimed at attenuating necrotic and apoptotic cell death, with the ultimate goal of
      applying these strategies to reduce infarct size and improve outcome in patients
      suffering acute myocardial infarction (MI) or 'heart attack'. However, an issue
      that remains controversial is the role of autophagy in determining the fate of
      ischemic-reperfused cardiomyocytes: i.e., is induction of autophagy detrimental
      or protective? Recent data from our group obtained in the clinically relevant, in
      vivo swine model of acute MI provides novel evidence of a positive association
      between pharmacological upregulation of autophagy (achieved by administration of
      chloramphenicol succinate (CAPS)) and increased resistance to myocardial ischemia
      reperfusion injury.

PMID- 21187720
TI  - Autophagy and p62/sequestosome 1 generate neo-antimicrobial peptides (cryptides)
      from cytosolic proteins.

PMID- 21187721
TI  - Regulation of PINK1-Parkin-mediated mitophagy.
AB  - Parkinson disease (PD) is a devastating disorder of the nervous system for which
      no cure exists. Although the exact mechanisms involved in the pathogenesis of PD
      are unclear, very recently, a novel cellular process has been identified that
      promises great future potential. Two PD-associated genes have been found to
      converge on the emerging mitophagy pathway that links the two major cellular
      dysfunctions implicated in the pathogenesis of PD. Thereby, PINK1 and Parkin
      physically associate and functionally cooperate to identify and label damaged
      mitochondria for selective degradation via autophagy. PD-associated mutations in
      both genes disrupt mitophagy although through different mechanisms, revealing a
      sequential multistep process. Further key players that tie into this process have
      been identified and provide the framework for future research aiming at a
      complete dissection of this neuroprotective pathway. This may not only yield
      novel targets for therapeutic intervention in PD, but possibly for other
      neurodegenerative disorders as well.

PMID- 21187722
TI  - Introduction to: magnetic resonance imaging of white matter diseases.

PMID- 21187723
TI  - Magnetic resonance imaging techniques in white matter disease: potentials and
      limitations.
AB  - OBJECTIVES: excellent soft tissue contrast, noninvasiveness, assessment of
      multiple structural and functional parameters, and absence of radiation are the
      essential properties of magnetic resonance imaging explaining why this modality
      is the technique of choice for the assessment of cerebral white matter (WM).
      METHODS: the present review discusses various standard and advance magnetic
      resonance imaging techniques with respect to WM assessment in a clinical context.
      Techniques assessing predominantly structure are T2, fluid-attenuated inversion
      recovery, echo-gradient T2*, and susceptibility weighted imaging. Techniques
      assessing a mix between structure and function are diffusion-weighted and
      diffusion tensor imaging to investigate WM tracts, magnetization transfer to
      assess bound and free water pool, and magnetic resonance spectroscopy
      investigating brain metabolites. Finally, functional techniques are perfusion
      weighted imaging and perfusion reserve imaging to assess cerebral perfusion and
      cerebral perfusion reserve, respectively. CONCLUSIONS: magnetic resonance imaging
      may assess various and complementary WM parameters. Because acquisition time is
      limited in the clinical setting, MR techniques must be adapted to the primary
      question asked. The basic imaging of WM might include axial T2, diffusion
      weighted imaging, and coronal fluid-attenuated inversion recovery. This provides
      an excellent overview in a relatively short time and 2 imaging planes. The
      remaining MR techniques can add complementary information, for example,
      PWI/perfusion reserve imaging in vascular disease, T2*/susceptibility weighted
      imaging in degenerative disease (iron deposition) and head trauma (microbleeds),
      magnetic resonance spectroscopy (metabolic disease and neoplasm), magnetization
      transfer (demyelinating disease), and diffusion tensor imaging (degenerative
      diseases, presurgical evaluation).

PMID- 21187724
TI  - Magnetic resonance imaging in multiple sclerosis.
AB  - OBJECTIVES: multiple sclerosis (MS) is an inflammatory disease of unknown origin
      affecting the central nervous system. Magnetic resonance imaging (MRI) plays an
      increasingly important role in its diagnosis and further monitoring of disease
      progress. METHODS: the typical MRI appearance of MS on conventional MRI sequences
      and current diagnostic criteria for MS are discussed. Advanced imaging techniques
      are reviewed with respect to application in MS. Finally, the atypical variants of
      MS are briefly reviewed. CONCLUSIONS: although MRI is not intended and will not
      replace clinical assessment in MS, the recognized MRI criteria may aid in
      establishing an earlier and more accurate diagnosis of MS in the context of a
      clinical suspicion or clinically isolated syndrome. In addition, MRI might
      contribute to rule out differential diagnoses for MS. Moreover, MRI may be used
      to monitor the evolution of MS and in pharmaceutical trials. Advanced imaging
      techniques might, in the future, further characterize MS lesion subtypes and
      potentially guide tailored therapy.

PMID- 21187725
TI  - Magnetic resonance imaging of infections of the white matter.
AB  - Infections of the nervous system are a common and serious occurrence.
      Neuroimaging has allowed to improve early detection and thus to initiate
      treatment earlier. Magnetic resonance (MR) imaging has become the method of
      choice in investigating a patient with suspicion of an infection of the central
      nervous system. Newer modalities such as MR spectroscopy and MR diffusion and
      perfusion will further help to improve diagnostic accuracy of the technique. For
      the investigation of infections of white matter, techniques such as diffusion
      imaging are essential.

PMID- 21187726
TI  - Magnetic resonance imaging of metabolic diseases of the cerebral white matter.
AB  - Metabolic diseases of the brain are a rare occurrence. They may be either
      occurring as inherited diseases causing a destruction of myelin, or they may be
      the result of toxicity. Neuroimaging, especially magnetic resonance imaging,
      plays an important role in the detection and classification of these rare
      diseases. Magnetic resonance spectroscopy is an important tool in the
      characterization and diagnosis of inherited metabolic diseases.

PMID- 21187727
TI  - Magnetic resonance imaging of vascular diseases of the white matter.
AB  - Magnetic resonance imaging plays an important role in the diagnosis and
      management of cerebrovascular diseases. In addition to stroke, it can also
      demonstrate changes apparent in the white matter such as leukoaraiosis. These as
      well as other changes occurring with increasing age can be visualized. Among
      others, there is an increase in the number and size of perivascular spaces.
      Although many of these alterations may be clinically silent, with increasing load
      they may become symptomatic. Other vascular pathological findings such as
      cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy and the posterior reversible encephalopathy syndrome can also
      provoke changes in the cerebral white matter that are visible on magnetic
      resonance imaging and are discussed.

PMID- 21187728
TI  - Hold, raise, or fold: C-reactive protein, hormone therapy, and cardiovascular
      risk.

PMID- 21187729
TI  - Systemic safety of bilateral intravitreal anti-vascular endothelial growth factor
      injections.

PMID- 21187730
TI  - Pharmacologic therapy of pseudophakic cystoid macular edema: 2010 update.
AB  - PURPOSE: To review the current management and pharmacologic treatment of
      pseudophakic cystoid macular edema. METHODS: Systematic review of currently
      accepted treatment modalities for pseudophakic cystoid macular edema. Main
      outcome measures include visual acuity and retinal thickness measurement by
      optical coherence tomography. RESULTS: Optical coherence tomography is used to
      diagnose and monitor response to therapy. New topical nonsteroidal
      antiinflammatory drugs have been approved by the Food and Drug Administration for
      ophthalmic use, and some show promise in the treatment of pseudophakic cystoid
      macular edema. Other areas of clinical research include the use of anti-vascular
      endothelial growth factor agents and the addition of intravitreal routes of
      administration (e.g., corticosteroids, nonsteroidal antiinflammatory drugs, and
      anti-vascular endothelial growth factor agents). Surgical therapeutic options
      include Nd:YAG laser for anterior vitreolysis and pars plana vitrectomy for
      chronic refractory cases. CONCLUSION: Surprisingly, few changes have occurred in
      recent years in the treatment of pseudophakic cystoid macular edema. Placebo
      controlled, double-masked, randomized, clinical trials are largely lacking.

PMID- 21187731
TI  - Bilateral intravitreal injection of antivascular endothelial growth factor
      therapy.
AB  - PURPOSE: The purpose of this study was to review adverse events and patient
      preference after bilateral intravitreal injection of antibodies to vascular
      endothelial growth factor. METHODS: A retrospective case-control study. Patients
      with exudative age-related macular degeneration who received intravitreal
      antivascular endothelial growth factor agent injections in both eyes (bilateral
      group) on the same day over a 23-month period were compared with patients who
      received injections in only 1 eye. The occurrence of endophthalmitis,
      cerebrovascular accident, myocardial infarction, death, patient discomfort, and
      patient preference was compared between the two groups. RESULTS: One hundred and
      two patients received an average of 4.43 bilateral injections (range 1-13). A
      case-control group of 102 patients received an average of 10.2 unilateral
      injections, (range 2-28). Bevacizumab was injected 45.5%, ranibizumab 45.5%, and
      a combination of bevacizumab and ranibizumab 9% of the time for bilateral
      injections. Bevacizumab was used 50.3% and ranubizumab 49.7% of the time in
      unilateral injections. The follow-up of both groups averaged 18.4 months (range
      4.7-36.5 months). There were no cases of endophthalmitis or cerebrovascular
      accident in either group. There was a single case of myocardial infarction in
      each group. There were two deaths in the bilateral group and three deaths in the
      unilateral group. More than 90% strongly preferred bilateral injections to
      unilateral injections. CONCLUSION: Bilateral injections of antivascular
      endothelial growth factor agents on the same day did not increase the rate of
      adverse events and was preferred by the majority of patients.

PMID- 21187732
TI  - Combination therapy of ranibizumab and photodynamic therapy for retinal
      angiomatous proliferation with serous pigment epithelial detachment in Korean
      patients: twelve-month results.
AB  - PURPOSE: The purpose of this study was to evaluate the safety and efficacy of
      combination therapy with intravitreal ranibizumab and photodynamic therapy in the
      treatment of retinal angiomatous proliferation (RAP) with serous pigment
      epithelial detachment. METHODS: Ten eyes of nine consecutive patients with newly
      diagnosed RAP were enrolled in this prospective pilot study. A course of
      combination therapy consisted of three ranibizumab injections at monthly
      intervals and a single photodynamic therapy, guided by indocyanine green
      angiography, about 1 week after the first injection. The patients were followed
      every month for 12 months. Retreatment was administered when a persistent,
      recurrent, or new RAP lesion was confirmed. RESULTS: Eight of the 9 patients (9
      eyes) completed 12 months of follow-up. At the 3-month visit, 8 of the 9 eyes
      (89%) showed favorable initial responses. After 6 months, recurrent lesions
      developed in 2 eyes (25%) and a new lesion in one other eye; all showed favorable
      responses to retreatment. At the 12-month visit, 7 eyes (78%) showed regression
      of the RAP lesions, among which 5 eyes (56%) required only a single session of
      combination treatment. The mean best-corrected visual acuity was improved from
      20/125 at baseline to 20/63 (P = 0.021), and the mean central foveal thickness
      was reduced from 353 MUm at baseline to 169 MUm (P = 0.017). The mean improvement
      in the best-corrected visual acuity was 3.86 lines. No patient had vision
      threatening adverse events. CONCLUSION: Ranibizumab and photodynamic therapy
      combination therapy appears to be safe and effective for anatomical and
      functional improvement in patients with RAP with pigment epithelial detachment.
      Further evaluation with a larger patient sample and a long-term controlled study
      is required to compare treatment efficacy with antivascular endothelial growth
      factor monotreatment.

PMID- 21187733
TI  - Correlation between visual prognosis and fundus autofluorescence and optical
      coherence tomographic findings in highly myopic eyes with submacular hemorrhage
      and without choroidal neovascularization.
AB  - PURPOSE: To determine whether a significant correlation existed between the
      visual prognosis and fundus autofluorescence and optical coherence tomographic
      images in highly myopic eyes with simple macular bleeding. METHODS: We reviewed
      the charts of 31 eyes of 28 patients with high myopia and simple bleeding. The
      patients were divided into those whose best-corrected visual acuity (BCVA) was
      20/32 and those with BCVA <20/32 at 6 months after absorption of the hemorrhage.
      RESULTS: At 6 months, 19 eyes had BCVA >=0.7 and 12 eyes had BCVA <0.7. In the
      former group, the inner segment/outer segment line of photoreceptors was intact
      in optical coherence tomographic images at the onset but was defective in 75% of
      the eyes in the latter group. At 6 months, the inner segment/outer segment defect
      was absent in all the eyes in the former group but was observed in 67% of the
      latter group. A hypoautofluorescence was present at the area of the bleeding more
      frequently in the poor BCVA groups. CONCLUSION: An inner segment/outer segment
      defect at the onset of simple bleeding might be a useful sign to predict a
      limited visual recovery. The persistent hypofluorescence in fundus
      autofluorescence is probably caused by damage to the retinal pigment epithelium
      by the subretinal hemorrhage.

PMID- 21187734
TI  - Stage 1-A macular hole: a prospective spectral-domain optical coherence
      tomography study.
AB  - PURPOSE: To determine the anatomical morphology of Stage 1-A impending macular
      holes characterized by a yellow spot using spectral-domain optical coherence
      tomography to study the fellow eyes of patients diagnosed with a full-thickness
      macular hole or eyes with a typical yellow spot with metamorphopsia. METHODS:
      Prospective observational case series of 45 patients with a full-thickness
      macular hole or a foveolar yellow spot with metamorphopsia. Visual acuity
      assessment, biomicroscopic examination, and spectral-domain optical coherence
      tomography were performed. Clinical ophthalmologic examinations were repeated,
      including spectral-domain optical coherence tomography, in the eyes with a
      foveolar yellow spot at 1-month interval. RESULTS: We examined 43 fellow eyes of
      43 patients with a macular hole and 2 eyes of 2 patients with a foveolar yellow
      spot. Five fellow eyes had a yellow spot. Spectral-domain optical coherence
      tomography clearly showed the reflectivity of the perifoveal posterior vitreous
      detachment with vitreofoveal adhesion in the 7 eyes with a yellow spot; the
      foveal microstructure had a triangular foveolar detachment of the cone outer
      segment tip line, of which only 2 eyes (29%) had foveal splits during the
      observational period, 3 eyes (43%) had a foveal perpendicular line, and 4 eyes
      (57%) showed progression to vitreofoveal separation before the development of
      inner splits or pseudocysts. In those 7 eyes, the 2 eyes (29%) with foveal splits
      progressed to a full-thickness macular hole. The 38 fellow eyes without a yellow
      spot had no foveolar detachment. CONCLUSION: The foveolar detachment of the cone
      outer segment tip line might be responsible for the yellow spot seen in Stage 1-A
      macular holes.

PMID- 21187735
TI  - Transcorneal three-port vitrectomy without conjunctival incision.

PMID- 21187736
TI  - A novel vitreoretinal dissector for use in vitrectomy.

PMID- 21187737
TI  - Preretinal and intraretinal exudates in familial exudative vitreoretinopathy.

PMID- 21187738
TI  - Doseof intravitreal bevacizumab [Avastin] used as preoperative adjunct therapy
      for proliferative diabetic retinopathy.

PMID- 21187741
TI  - The long-term data of photodynamic therapy (PDT) for polypoidal choroidal
      vasculopathy (PCV).

PMID- 21187745
TI  - Targeted temperature management in critical care: a report and recommendations
      from five professional societies.
AB  - OBJECTIVE: Representatives of five international critical care societies convened
      topic specialists and a nonexpert jury to review, assess, and report on studies
      of targeted temperature management and to provide clinical recommendations. DATA
      SOURCES: Questions were allocated to experts who reviewed their areas, made
      formal presentations, and responded to questions. Jurors also performed
      independent searches. Sources used for consensus derived exclusively from peer
      reviewed reports of human and animal studies. STUDY SELECTION: Question-specific
      studies were selected from literature searches; jurors independently determined
      the relevance of each study included in the synthesis. CONCLUSIONS AND
      RECOMMENDATIONS: 1) The jury opines that the term "targeted temperature
      management" replace "therapeutic hypothermia." 2) The jury opines that
      descriptors (e.g., "mild") be replaced with explicit targeted temperature
      management profiles. 3) The jury opines that each report of a targeted
      temperature management trial enumerate the physiologic effects anticipated by the
      investigators and actually observed and/or measured in subjects in each arm of
      the trial as a strategy for increasing knowledge of the dose/duration/response
      characteristics of temperature management. This enumeration should be kept
      separate from the body of the report, be organized by body systems, and be made
      without assertions about the impact of any specific effect on the clinical
      outcome. 4) The jury STRONGLY RECOMMENDS targeted temperature management to a
      target of 32 degrees C-34 degrees C as the preferred treatment (vs. unstructured
      temperature management) of out-of-hospital adult cardiac arrest victims with a
      first registered electrocardiography rhythm of ventricular fibrillation or
      pulseless ventricular tachycardia and still unconscious after restoration of
      spontaneous circulation (strong recommendation, moderate quality of evidence). 5)
      The jury WEAKLY RECOMMENDS the use of targeted temperature management to 33
      degrees C-35.5 degrees C (vs. less structured management) in the treatment of
      term newborns who sustained asphyxia and exhibit acidosis and/or encephalopathy
      (weak recommendation, moderate quality of evidence).

PMID- 21187747
TI  - A porcine model for initial surge mechanical ventilator assessment and evaluation
      of two limited-function ventilators.
AB  - OBJECTIVES: To adapt an animal model of acute lung injury for use as a standard
      protocol for a screening initial evaluation of limited function, or "surge,"
      ventilators for use in mass casualty scenarios. DESIGN: Prospective, experimental
      animal study. SETTING: University research laboratory. SUBJECTS: Twelve adult
      pigs. INTERVENTIONS: Twelve spontaneously breathing pigs (six in each group) were
      subjected to acute lung injury/acute respiratory distress syndrome via pulmonary
      artery infusion of oleic acid. After development of respiratory failure, animals
      were mechanically ventilated with a limited-function ventilator (simplified
      automatic ventilator [SAVe] I or II; Automedx, Germantown, MD) for 1 hr or until
      the ventilator could not support the animal. The limited-function ventilator was
      then exchanged for a full-function ventilator (Servo 900C; Siemens-Elema, Solna,
      Sweden). MEASUREMENTS AND MAIN RESULTS: Reliable and reproducible levels of acute
      lung injury/acute respiratory distress syndrome were induced. The SAVe I was
      unable to adequately oxygenate five animals with Pao2 (52.0+/-11.1 torr) compared
      to the Servo (106.0+/-25.6 torr; p=.002). The SAVe II was able to oxygenate and
      ventilate all six animals for 1 hr with no difference in Pao2 (141.8+/-169.3
      torr) compared to the Servo (158.3+/-167.7 torr). CONCLUSIONS: We describe a
      novel in vivo model of acute lung injury/acute respiratory distress syndrome that
      can be used to initially screen limited-function ventilators considered for mass
      respiratory failure stockpiles and that is intended to be combined with
      additional studies to definitively assess appropriateness for mass respiratory
      failure. Specifically, during this study we demonstrate that the SAVe I
      ventilator is unable to provide sufficient gas exchange, whereas the SAVe II,
      with several more functions, was able to support the same level of hypoxemic
      respiratory failure secondary to acute lung injury/acute respiratory distress
      syndrome for 1 hr.

PMID- 21187746
TI  - The effect of race and ethnicity on outcomes among patients in the intensive care
      unit: a comprehensive study involving socioeconomic status and resuscitation
      preferences.
AB  - OBJECTIVE: We sought to determine whether race or ethnicity is independently
      associated with mortality or intensive care unit length of stay among critically
      ill patients after accounting for patients' clinical and demographic
      characteristics including socioeconomic status and resuscitation preferences.
      DESIGN: Historical cohort study of patients hospitalized in intensive care units.
      SETTING: Adult intensive care units in 35 California hospitals during the years
      2001-2004. PATIENTS: A total of 9,518 intensive care unit patients (6,334 white,
      655 black, 1,917 Hispanic, and 612 Asian/Pacific Islander patients). MEASUREMENTS
      AND MAIN RESULTS: The primary outcome was risk-adjusted mortality and a secondary
      outcome was risk-adjusted intensive care unit length of stay. Crude hospital
      mortality was 15.9% among the entire cohort. Asian patients had the highest crude
      hospital mortality at 18.6% and black patients had the lowest at 15.0%. After
      adjusting for age and gender, Hispanic and Asian patients had a higher risk of
      death compared to white patients, but these differences were not significant
      after additional adjustment for severity of illness. Black patients had more
      acute physiologic derangements at intensive care unit admission and longer
      unadjusted intensive care unit lengths of stay. Intensive care unit length of
      stay was not significantly different among racial/ethnic groups after adjustment
      for demographic, clinical, and socioeconomic factors and do-not-resuscitate
      status. In an analysis restricted only to those who died, decedent black patients
      averaged 1.1 additional days in the intensive care unit (95% confidence interval,
      0.26-2.6) compared to white patients who died, although this was not
      statistically significant. CONCLUSIONS: Hospital mortality and intensive care
      unit length of stay did not differ by race or ethnicity among this diverse cohort
      of critically ill patients after adjustment for severity of illness,
      resuscitation status, socioeconomic status, insurance status, and admission type.
      Black patients had more acute physiologic derangements at intensive care unit
      admission and were less likely to have a do-not-resuscitate order. These results
      suggest that among intensive care unit patients, there are no racial or ethnic
      differences in mortality within individual hospitals. If disparities in intensive
      care unit care exist, they may be explained by differences in the quality of care
      provided by hospitals that serve high proportions of minority patients.

PMID- 21187748
TI  - Standardized experimental brain death model for studies of intracranial dynamics,
      organ preservation, and organ transplantation in the pig.
AB  - OBJECTIVES: Brain death impairs organ function and outcome after transplantation.
      There is a need for a brain death model to allow studies of organ viability and
      preservation. For neurointensive care research, it is also of interest to have a
      relevant brain death model for studies of intracranial dynamics and evaluation of
      cerebral monitoring devices. Therefore, the objective was to develop a
      standardized clinically relevant brain death model. METHODS: Six pigs of both
      sexes (10-12 wks old; mean weight, 24.5+/-1.4 kg) were included. Mean arterial
      blood pressure, heart rate, intracranial pressure, intracranial compliance,
      cerebral perfusion pressure, and brain tissue oxygenation (BtiPo2) were recorded
      during stepwise elevation of intracranial pressure by inflation of an epidural
      balloon catheter with saline (1 mL/20 mins). Brain death criteria were decided to
      be reached when cerebral perfusion pressure was <0 mm Hg for 60 mins and at least
      10 mL saline was inflated epidurally. BtiPo2 and arterial injections of
      microspheres were used for confirmation of brain death. RESULTS: A gradual volume
      dependent elevation of intracranial pressure was observed. After 10 mL of balloon
      infusion, mean intracranial pressure was 89.8+/-9.7 (sd) mm Hg. Intracranial
      compliance decreased from 0.137+/-0.069 mL/mm Hg to 0.007+/-0.001 mL/mm Hg. The
      mean arterial pressure decreased and the heart rate increased when the
      intracranial volume was increased to between 5 and 6 mL. All animals showed
      cerebral perfusion pressure<=0 after 7 to 10 mL of infusion. In all animals, the
      criteria for brain death with negative cerebral perfusion pressure and BtiPo2 ~0
      mm Hg were achieved. Only a negligible amount of microspheres were found in the
      cerebrum, confirming brain death. The kidneys showed small foci of acute tubular
      necrosis. CONCLUSIONS: The standardized brain death model designed in pigs
      simulates the clinical development of brain death in humans with a classic
      pressure-volume response and systemic cardiovascular reactions. Brain death was
      convincingly confirmed.

PMID- 21187749
TI  - The perception of sentence stress in cochlear implant recipients.
AB  - OBJECTIVES: Sentence stress is a vital attribute of speech since it indicates the
      importance of specific words within an utterance. Basic acoustic correlates of
      stress are syllable duration, intensity, and fundamental frequency (F0).
      Objectives of the study were to determine cochlear implant (CI) users' perception
      of the acoustic correlates and to uncover which cues are used for stress
      identification. DESIGN: Several experiments addressed the discrimination of
      changes in syllable duration, intensity, and F0 as well as stress identification
      based on these cues. Moreover, the discrimination of combined cues and
      identification of stress in conversational speech was examined. Both natural
      utterances and artificial manipulations of the acoustic cues were used as
      stimuli. RESULTS: Discrimination of syllable duration did not differ
      significantly between CI recipients and a control group of normal-hearing
      listeners. In contrast, CI users performed significantly worse on tasks of
      discrimination and stress identification based on F0 as well as on intensity.
      Results from these measurements were significantly correlated with the ability to
      identify stress in conversational speech. Discrimination performance for
      covarying F0 and intensity changes was more strongly correlated to identification
      performance than was found for discrimination of either F0 or intensity alone.
      Syllable duration was not related to stress identification in natural utterances.
      CONCLUSIONS: The outcome emphasizes the importance of both F0 and intensity for
      CI users' identification of sentence-based stress. Both cues were used separately
      for stress perception, but combining the cues provided extra benefit for most of
      the subjects.

PMID- 21187750
TI  - The efficiency of the single- versus multiple-stimulus auditory steady state
      responses in infants.
AB  - OBJECTIVES: Multiple auditory steady state responses (ASSRs) will likely be
      included in the diagnostic test battery for estimating infant auditory thresholds
      in the near future; however, the effects of single- versus multiple-stimulus
      presentation in infants has never been investigated. In adults, there are no
      interactions (reduced amplitudes) between responses to multiple simultaneous
      stimuli presented at 60 dB SPL or lower. Maturational differences, however, may
      lead to greater interactions in infants; thus, it is unknown whether the single
      stimulus technique or the multiple-stimulus technique is more efficient for
      testing infants. Two studies were carried out to address this issue. DESIGN: All
      infants in study A participated in three stimulus conditions, which differed in
      the number of stimuli presented simultaneously. The monotic single (MS) condition
      consisted of 500, 1000, 2000, and 4000 Hz tones, which were presented singly to
      one ear. The monotic multiple (MM) condition was composed of four tones (500,
      1000, 2000, and 4000 Hz) presented to one ear simultaneously. The dichotic
      multiple (DM) condition consisted of eight tones presented simultaneously to both
      ears (four tones to each ear). ASSR amplitudes were obtained from 15 normal
      infants (mean age: 23.1 wks) in response to multiple (MM, DM) and single (MS) air
      conduction amplitude-modulated (AM) tones (77 to 105 Hz modulation rates; 60 dB
      SPL). In study B, ASSR thresholds were determined for 500-Hz stimuli in the
      single- and DM-stimulus conditions (14 infants; mean age: 20.2 wks). RESULTS:
      Mean single-stimulus ASSR amplitudes for 500, 1000, 2000, and 4000 Hz were 30,
      39, 45 and 43 nV, respectively. Presentation of multiple AM tones (i.e., four
      octave-spaced frequencies) to one ear resulted in ASSR amplitudes that were 97%,
      87%, 82%, and 70% (for 500, 1000, 2000, and 4000 Hz, respectively) of the single
      stimulus ASSR amplitudes. Results for the dichotic presentation of eight AM tones
      show ASSR amplitudes that were 70%, 77%, 67%, and 67% relative to the MS
      condition. Although decreases in amplitude occurred using multiple stimuli in
      infants, the multiple ASSR remained more efficient than the single-stimulus ASSR
      (i.e., multiple-stimulus amplitudes were greater than single-stimulus amplitudes
      divided by ?K, where K is the number of stimuli). Results from study B indicate
      that ASSR thresholds for 500 Hz presented in the DM condition were elevated 3 dB
      compared with that obtained in the 500-Hz single-stimulus condition. This
      statistically nonsignificant difference is within the range of acceptable test
      retest variability and is thus not of clinical significance. CONCLUSIONS: The
      amplitude reductions seen in the multiple-stimulus conditions in infants, not
      seen in adults, could be related to maturational differences in the ear canal,
      middle ear, cochlea, and/or brain stem. Because greater interactions occur in the
      DM-stimulus condition compared with the monotic multiple-stimulus condition and
      baseline single-stimulus condition, brain stem origins of these interactions are
      likely. Study B revealed statistically nonsignificant differences between
      threshold for 500 Hz when presented in the single- and DM-stimulus conditions. In
      summary, as with adults, multiple-stimulus presentation in infants is more
      efficient than single AM tones, at least for 60 dB SPL stimuli.

PMID- 21187751
TI  - Level discrimination of speech sounds by hearing-impaired individuals with and
      without hearing amplification.
AB  - OBJECTIVES: The current study was designed to see how hearing-impaired
      individuals judge level differences between speech sounds with and without
      hearing amplification. It was hypothesized that hearing aid compression should
      adversely affect the user's ability to judge level differences. DESIGN: Thirty
      eight hearing-impaired participants performed an adaptive tracking procedure to
      determine their level-discrimination thresholds for different word and sentence
      tokens, as well as speech-spectrum noise, with and without their hearing aids.
      Eight normal-hearing participants performed the same task for comparison.
      RESULTS: Level discrimination for different word and sentence tokens was more
      difficult than the discrimination of stationary noises. Word level discrimination
      was significantly more difficult than sentence level discrimination. There were
      no significant differences, however, between mean performance with and without
      hearing aids and no correlations between performance and various hearing aid
      measurements. CONCLUSIONS: There is a clear difficulty in judging the level
      differences between words or sentences relative to differences between broadband
      noises, but this difficulty was found for both hearing-impaired and normal
      hearing individuals and had no relation to hearing aid compression measures. The
      lack of a clear adverse effect of hearing aid compression on level discrimination
      is suggested to be due to the low effective compression ratios of currently fit
      hearing aids.

PMID- 21187753
TI  - Severe deformational plagiocephaly: long-term results of surgical treatment.

PMID- 21187752
TI  - Electrically evoked compound action potential measures for virtual channels
      versus physical electrodes.
AB  - OBJECTIVES: The number of distinct pitch percepts for cochlear implant (CI)
      listeners is somewhat limited by the number of physical electrodes in the array.
      Newer-generation CIs have the capability to potentially increase this number by
      stimulating areas of the cochlea between the physical electrodes. Currently, this
      is achieved by electrically coupling adjacent electrodes or by simultaneously
      activating two electrodes with independent current sources (i.e., current
      steering). Presumably, either type of dual-electrode stimulation will generate
      neural excitation patterns that are intermediate to those generated by either
      physical electrode alone (henceforth termed virtual channel). However, it is not
      clear whether virtual-channel stimulation yields neural recruitment patterns with
      similar shapes and rates of growth as compared with each physical electrode
      alone. The purpose of this study was to compare basic electrically evoked
      compound action potential (ECAP) measures for physical electrodes and virtual
      channels to determine whether properties of the respective excitation patterns
      were similar. DESIGN: Data were collected for 12 adult CI recipients (six Nucleus
      Freedom CI24RE, two Advanced Bionics HiResolution 90K, and four Advanced Bionics
      CII). ECAP responses were measured for a set of three adjacent physical
      electrodes and two corresponding intermediate virtual channels (e.g., physical
      electrodes 4, 5, and 6 and virtual channels 4 + 5 and 5 + 6) at three positions
      along the electrode array (basal, middle, and apical). Virtual channels for
      Nucleus subjects were produced via electrical coupling of adjacent electrode
      pairs (dual-electrode mode). For Advanced Bionics subjects, virtual channels were
      produced via simultaneous, in-phase stimulation of adjacent electrode pairs with
      50% of the total current delivered to each electrode in the pair. Specific ECAP
      measures were as follows: (1) threshold and slope of the input/output functions,
      (2) amplitude for a masker-probe interval of 1500 MUsecs (measure of refractory
      recovery), and (3) relative location of spread of excitation (SOE) functions
      among virtual channels and adjacent physical electrodes. Measures for virtual
      channels were compared with those for the flanking physical electrodes using a
      multivariate analysis of variance. RESULTS: There were no statistically
      significant differences between physical electrodes and virtual channels for ECAP
      thresholds, slope of the input/output function, or refractory recovery. On
      average, SOE functions for the virtual channels were spatially located
      approximately halfway between SOE functions for the adjacent physical electrodes.
      CONCLUSIONS: Results from this study suggest that virtual channels produce neural
      recruitment patterns with properties similar to those elicited by the adjacent
      physical electrodes.

PMID- 21187754
TI  - Severe deformational plagiocephaly: long-term results of surgical treatment.
AB  - INTRODUCTION: Deformational plagiocephaly (DP), a benign infantile condition, is
      often thought to improve spontaneously but can in fact lead to permanent skull
      asymmetry if left untreated. Deformational plagiocephaly can be completely
      corrected by nonsurgical treatments if recognized in the first year of life.
      Nevertheless, efficacy of these treatments drastically diminishes after 9 months
      as the calvaria thickens. Beyond 15 months, if the asymmetry is severe, surgical
      remodeling becomes an option. In this study, we analyzed the surgical morbidities
      and the morphologic outcome of surgical remodeling in DP. METHODS: This study was
      designed as a retrospective analysis of a craniofacial database combined with an
      outcome study. Between January 1992 and August 2006, 2363 occipital DP cases were
      treated by repositioning. Thirty patients were operated on, always after the age
      of 15 months (1.23%). Mean (SD) age at the time of the first clinic was 19.2 (+/-
      5.8) months (range, 11-34 mo). A switch cranioplasty (A) was first used,
      progressively replaced since 1995 by a large occipital monobloc graft rotated 180
      degrees and fixed with tongue-in-groove pillars (B). Morbidities were extracted
      from the database. Long-term morphologic outcomes were evaluated during a free
      clinic visit with a 4-point Likert-type outcome scale. RESULTS: Mean (SD) age at
      the time of surgery was 20.2 (+/- 5.6) months. Incidents (dural tears or venous
      sinus breaches) occurred in 28% (A) and 36% (B) or patients. One complication
      required repeat operation (extradural hematoma). No cerebrospinal fluid leaks
      and/or meningitis were recorded. Mean (SD) hospital stay was 5.3 (+/- 0.95) days.
      There was no statistical difference in the long-term morphologic outcome between
      the 2 groups (median of group A being "good but still visible"; median of group B
      being "excellent, unnoticeable"). CONCLUSIONS: Surgical correction of DP is a
      potentially life-threatening procedure, which should be indicated only in very
      severe cases, after exhaustion of all other nonsurgical methods, in a reference
      craniofacial center combining pediatric neurosurgery and plastic surgery.

PMID- 21187755
TI  - Aplasia cutis congenita: clinical management of a rare congenital anomaly.
AB  - BACKGROUND: Aplasia cutis congenita (ACC) is a rare congenital disorder
      characterized by absence of skin and adjacent tissue that usually affects the
      scalp, but any part of the body may be affected. Although ACC is more often
      superficial and small, it can be large and involve the underlying structures such
      as skull and dura, thus increasing the risk of hemorrhage, infection, and
      mortality. Controversy exists regarding nonsurgical versus surgical intervention
      for this condition. This study reviews indications and modalities for treatment
      of this rare congenital anomaly. RESULTS: Management of this anomaly depends on
      size, location, and structures at risk. Small lesions with intact underlying
      structures and lesions affecting extremities are treated in a conservative
      fashion with dressings and ointments followed by delayed scar excision. Aplasia
      cutis congenita scar excision often requires complex tissue rearrangement, tissue
      expansion, or skin grafting. Larger ACC lesions or lesions with exposure of vital
      structures require early surgical intervention. Initially, exposed vital
      structures and bony ridges can be protected using conservative measures. Delayed
      definitive repair can then be performed using scalp flaps, split- and full
      thickness skin grafts, cultured epithelial autografts, delayed split rib
      cranioplasty, tissue expansion, and composite cranioplasty. CONCLUSIONS: Aplasia
      cutis congenita should be individually evaluated based on size, depth, location,
      and tissues involved. Using conservative and surgical modalities, one can achieve
      complete closure of the defect, thus avoiding risks of infection, hemorrhage, and
      further trauma.

PMID- 21187756
TI  - Decortication of fibrous dysplasia of the maxillary sinus.
AB  - We present 3 cases of fibrous dysplasia of the maxillary sinus that were treated
      by decortication through the anterior wall of the maxilla. The thickened anterior
      wall of the maxilla and the zygoma were contoured into normal shape with a bur,
      and a 2 * 2-cm window was made below the infraorbital foramen using a
      reciprocating saw. The removed piece of bone was 3 to 5 mm thick. All abnormal
      fibrous tissues in the maxillary sinus were extirpated by drilling through the
      window until the sinus cavity was clear. The preserved bone plate was restored in
      place to close the window of the maxillary anterior wall and fixed with
      miniplates. Three patients were treated by means of such internal decompression
      method. No overgrowth or disfigurement of the facial bone was appreciated 14 to
      51 months postoperatively. We contend that internal decortication of fibrous
      dysplasia through a window in the anterior wall is effective to minimize external
      expansion of fibrous dysplasia.

PMID- 21187757
TI  - Lateral rectus muscle injury, orbital fracture, mouth locking, and facial palsy
      resulting from reduction malarplasty.
AB  - I report here on a patient with serious complications (lateral rectus muscle
      injury, orbital fracture, mouth locking, and facial palsy) that were caused by
      reduction malarplasty. A 32-year-old woman was referred to our department with
      complaints of inability to move her right eyeball laterally and inability to open
      her mouth. She has undergone reduction malarplasty 30 days previously at a local
      clinic. On examination, her maximal mouth opening was less than 3 mm. Her upper
      lip deviated to the left side when whistling. The orbit was displaced laterally
      and inferiorly. The upward and lateral gaze were limited. Computed tomography
      revealed fracture of the right orbital floor and lateral orbital wall extending
      to the orbital roof. The right lateral rectus muscle showed disconnection. The
      osteotomized segments were displaced inferiorly, and they pressed on the masseter
      muscle and coronoid process on the left side. On the 43rd postoperative day, a
      revision operation for the zygoma and orbit was carried out. Four days after the
      revision operation, surgery was performed for the myorrhaphy of the lateral
      rectus muscle and transposition of the medial rectus muscle. This case suggests
      the possibility of orbital fracture that can occur as a result of sawing in the
      wrong direction when using the intraoral approach. Although orbital fracture is
      extremely rare, it is hoped that this case will heighten the awareness of
      surgeons for this potential orbital fracture.

PMID- 21187758
TI  - Oral rehabilitation with implantations: association of fixed partial prosthesis,
      UCLA system, and EsthetiCone.
AB  - The objective of modern odontology is to reconstitute to the patient the comfort,
      the function, the aesthetic form, the phonetic capability, and normal health.
      However, the more the patient is toothless, the more this objective becomes
      difficult inside traditional dentistry. As a result of continuous research of
      materials and techniques, permissible success is now a reality, whitewashing many
      challenging clinical situations. Thus, the objective of the article was to
      present a clinical case where association of the universal cast to long abutment
      pillars and EsthetiCone were used for aesthetic whitewashing. A man presented to
      the clinic of the Faculty of Dentistry, Universidade Estadual Paulista. After
      clinical examination and radiographic evaluation evidenced the necessity of
      substitution of fixed prostheses (15-25), he was presented with disadaptation and
      a favorable aesthetic solution. Ahead of the evaluated picture and considering
      the extension of the toothless space made, it was opted more, to the
      accomplishment of surgery, the setting of 2 implantations in the region and 2 in
      each edentate side of the posterior portion of the jaw. On 6 implants and 2
      teeth, 10 metal ceramic crowns had been confectioned: 4 of them being joined in
      the region of the 12 to the 22 and the other 6 as unit crowns in the region of
      the 13, the 14, the 15, the 23, the 24, and the 25. The carried-through treatment
      was capable to return the aesthetic form, the function, the phonetic capability,
      the comfort, and the health of the verbal socket.

PMID- 21187759
TI  - Dentofacial deformities treated according to a dentoskeletal analysis based on
      the divine proportion: are the resulting faces de facto "divinely" proportioned?
AB  - The aim of this study was to retrospectively evaluate the accuracy and
      reliability of a skeletal cephalometric analysis based on the divine proportion
      (Sassouni's analysis) in predicting "divinely proportioned" faces in the
      treatment of dentofacial deformities. Preoperative and postoperative frontal
      photographs of 50 patients were analyzed, and the following 5 proportions were
      measured: (1) TR-AL:AL-ME, (2) ME-AL:AL-LC, (3) LC-CH:CH-ME, (4) LC-AL:AL-CH, and
      (5) ME-CH:CH-AL (TR indicates trichion; AL, alar rim; ME, menton; LC, lateral
      canthus; CH, cheilion). For each proportion, the effect of the treatment on the
      absolute difference between the proportions and the golden number (Phi) (1.618)
      was statistically analyzed. Analyses were adjusted for sex, age, type of
      dentofacial deformity (anteroposterior and/or vertical), and surgical technique
      (1-jaw vs 2-jaw surgery with or without a genioplasty). In all of the cases, the
      facial proportions analyzed were not significantly changed by the surgical
      treatment except for the proportion ME-CH:CH-AL (lower facial third), which was
      significantly moved toward 1.618 (P < 0.01). The current study demonstrated that
      (1) facial divine proportion can be closely approximated and predicted only by a
      specific cephalometric analysis in the lower facial third and (2) parameters such
      as age, sex, type of dentofacial deformities, type of surgery, and so on, could
      potentially and significantly influence the final results toward the divine
      proportion.

PMID- 21187760
TI  - A novel technique for presurgical nasoalveolar molding using computer-aided
      reverse engineering and rapid prototyping.
AB  - OBJECTIVE: To establish a new method of presurgical nasoalveolar molding (NAM)
      using computer-aided reverse engineering and rapid prototyping technique in
      infants with unilateral cleft lip and palate (UCLP). METHODS: Five infants (2
      males and 3 females with mean age of 1.2 w) with complete UCLP were recruited.
      All patients were subjected to NAM before the cleft lip repair. The upper denture
      casts were recorded using a three-dimensional laser scanner within 2 weeks after
      birth in UCLP infants. A digital model was constructed and analyzed to simulate
      the NAM procedure with reverse engineering software. The digital geometrical data
      were exported to print the solid model with rapid prototyping system. The whole
      set of appliances was fabricated based on these solid models. RESULTS: Laser
      scanning and digital model construction simplified the NAM procedure and
      estimated the treatment objective. The appliances were fabricated based on the
      rapid prototyping technique, and for each patient, the complete set of appliances
      could be obtained at one time. By the end of presurgical NAM treatment, the cleft
      was narrowed, and the malformation of nasoalveolar segments was aligned normally.
      CONCLUSIONS: We have developed a novel technique of presurgical NAM based on a
      computer-aided design. The accurate digital denture model of UCLP infants could
      be obtained with laser scanning. The treatment design and appliance fabrication
      could be simplified with a computer-aided reverse engineering and rapid
      prototyping technique.

PMID- 21187761
TI  - Validation of optical three-dimensional plagiocephalometry by computed
      tomography, direct measurement, and indirect measurements using thermoplastic
      bands.
AB  - The aim of the study was to validate optical three-dimensional surface imaging
      for plagiocephalometry by comparing it with established direct and indirect
      plagiocephalometric measurements. From head models with symmetric and asymmetric
      shapes, a number of distances were determined for plagiocephalometry. Data were
      acquired by optical three-dimensional surface imaging, direct and indirect
      measurements, and computed tomography. Data acquisition was repeated 10 times
      with each method. In 10 patients with positional plagiocephaly, optical three
      dimensional surface data were acquired, and thermoplastic strips were used to
      reproduce the largest circumferences of the patients' heads. All measurements
      were carried out by the same observer. The measurements for the head models were
      used to assess the reproducibility of the different measurement techniques and to
      check if there were statistically significant differences between them. The
      patient measurements were also used to determine if there were statistically
      significant differences between the different techniques in clinical use. None of
      the plagiocephalometric distances showed statistically significant differences
      when the 4 different methods were compared on the head models (P > 0.05).
      Comparison of plagiocephalometric distances obtained from optical three
      dimensional imaging and from thermoplastic strips in clinical use showed also no
      significant difference (P > 0.05). The results of the current study reveal that
      optical three-dimensional imaging is a relevant alternative to other established
      techniques in plagiocephalometry that should be tested in larger patient series.

PMID- 21187762
TI  - Impact of long-term nasopharyngeal airway on health-related quality of life of
      children with obstructive sleep apnea caused by syndromic craniosynostosis.
AB  - Obstructive sleep apnea in children with syndromic craniosynostosis is a well
      documented entity, and airway management in these group of children is difficult,
      with well-documented cardiorespiratory and neurodevelopment consequences.
      Numerous well-documented techniques are available for airway management in this
      group of children. In our center, the nasopharyngeal airway (NPA) is the first
      line treatment. This study aimed to evaluate the improvement in health-related
      quality of life in this group of children using the Glasgow Children's Benefit
      Inventory. We conducted a retrospective postal study of 24 patients with
      craniofacial disorders who had an NPA inserted as part of their airway
      management. A 79.2% (n = 19) response rate was obtained. Mean (SD) age was 5.8
      (4.1) years. Patients were classified into 3 main groups: Crouzon (n = 11), Apert
      (n = 6), and Pfeiffer (n = 2) syndromes. There was improvement in 3 of the 4
      domains, namely, learning (P = 0.006), vitality (P = 0.003), physical (range, -3
      to 8; mean, 2; P = 0.005). There was significant improvement in the sleep study
      parameters; however, no correlation was found between this and the Glasgow
      Children's Benefit Inventory findings. Parents also preferred an NPA as opposed
      to a tracheostomy when given a choice. Our study shows that NPA confers
      significant improvement not only in health-related quality of life but also in
      severity of obstructive sleep apnea as judged by sleep study parameters. The NPA
      is also well tolerated by patients and is much preferred by parents for airway
      management for their children as opposed to having a tracheostomy. We think that
      this should be considered in other centers as first-line management in children
      with syndromic craniosynostosis.

PMID- 21187763
TI  - Vertical position of the orbits in nonsyndromic plagiocephaly in childhood and
      its relation to vertical strabismus.
AB  - PURPOSE: To determine the existence of a correlation between the vertical angle
      of strabismus and the vertical angle between the orbital axes in nonsyndromic
      plagiocephaly in childhood. METHODS: Patients were included when diagnosed with
      plagiocephaly. Orthoptic measurements showed a vertical strabismus and three
      dimensional computed tomographic (CT) imaging of the skull was available.
      Patients were excluded if plagiocephaly was part of a syndrome or if any surgical
      intervention had taken place before our measurements. Three-dimensional CT
      imaging was used to calculate the vertical angle between the orbital axes in 3
      reference planes (VAO) perpendicular to a line of reference through the lower
      borders of the maxilla (VAOmax), both auditory canals (VAOaud), and the lower
      points of the external occipital protuberances (VAOocc). RESULTS: Fourteen
      patients were included (mean age, 14 mo). Three-dimensional CT measurements
      showed a mean (SD) VAOmax of 1.70 (2.31) degrees, VAOaud of -1.54 (1.46) degrees,
      and VAOocc of -2.06 (4.29) degrees (a negative value indicates that the eye on
      the affected side was situated lower in the head). The mean vertical angle of
      strabismus was -2.39 (4.69) degrees in gaze toward the affected side, 3.66 (3.77)
      degrees in gaze ahead, and 8.14 (5.63) degrees in gaze toward the nonaffected
      side. The Pearson test showed no significant correlations. CONCLUSIONS: The
      clinical observation that vertical strabismus in adult plagiocephaly is
      correlated with the vertical angle of the orbital axes could not be confirmed in
      young children.

PMID- 21187764
TI  - A new syndrome with craniosynostosis and cleft lip and palate.
AB  - Two unrelated girls with craniosynostosis and bilateral cleft lip and palate who
      also had developmental delay and umbilical herniae are presented. We propose that
      these patients have the same condition, and that their combination of features
      may constitute a new syndrome. Management of the patients is discussed.

PMID- 21187765
TI  - Effect of in vitro aging on the stiffness of bioabsorbable fixation plates.
AB  - The purpose of this study was to investigate the effect of in vitro aging on the
      stiffness of bioabsorbable fixation plates. Twenty-four polylactic/polyglycolic
      acid plates (LactoSorb; Lorenz, Jacksonville, FL) were divided in 3 groups of 8
      specimens each. Group A served as control, and groups B and C were immersed in
      0.1 M lactic acid for 15 and 30 days, respectively. All specimens were subjected
      to a 3-point bending test, using a universal testing machine, and the stiffness
      of each specimen was estimated. When analyzed with one-way analysis of variance,
      no difference was observed for the control and in vitro-aged specimens with
      regard to stiffness. Long-term (30 d) in vitro aging of poly-L-lactic acid
      bioabsorbable fixation plates does not seem to significantly affect the stiffness
      of the material as derived from a 3-point bending test.

PMID- 21187766
TI  - Anatomic survey of arachnoid foveolae and the clinical correlation to cranial
      bone grafting.
AB  - INTRODUCTION: When performing in situ harvesting of cranial bone grafts, there is
      a risk of entering the pericranial-intracranial venous system, either directly or
      indirectly through the arachnoid foveolae. The aims of this study were to
      investigate the size and location of arachnoid foveolae and to provide an
      anatomic road map to prevent penetrating these structures. METHODS: Three hundred
      dry skulls were selected from the Hamann-Todd osteological collection (Cleveland,
      OH); skulls were collected between 1912 and 1938. Our study skulls were limited
      to whites or African American adults. Exclusion criteria included children (<18
      y), ethnic groups other than African Americans and whites, skulls demonstrating
      fracture or craniofacial abnormalities, or any skull whose age, ethnicity, and
      sex could not be confirmed. From the 300 skulls in the collection, 200 met the
      criteria and were included in our review. The mean age of these 200 individuals
      was 43.86 years, with a male-to-female proportion of 100:100, and a white-to
      African American proportion of 144:56. A 500-W candescent light was used to
      transilluminate the arachnoid foveola, and digital photographs with scale were
      obtained. The location and diameters of foveolae for arachnoid granulations
      relative to the coronal and sagittal suture were measured. CONCLUSIONS:
      Approximately 90% of major arachnoid foveolae are located within 2.5 cm of the
      coronal and 1.5 cm of the sagittal suture for the left and right parietal bones.
      Major arachnoid foveolae are located at closer distances to the superior sagittal
      suture and the coronal suture in the right and left parietal bone than minor
      foveolae. The results of this study imply that potential complications can be
      minimized by avoiding these areas and by harvesting in situ bone grafts from the
      absolute and relative safe zones described in this study.

PMID- 21187767
TI  - Mechanical characterization and optoelectronic measurement of parietal bone
      thickness before and after monocortical bone graft harvest: design and validation
      of a test protocol.
AB  - Parietal bone grafts are commonly used in craniomaxillofacial surgery. However,
      bone removal may weaken the parietal bone and lead to deleterious complications.
      The aim of our study was to design a test protocol for characterization of the
      impact resistance of parietal bone before and after monocortical bone graft
      harvest and to validate an optoelectronic measurement of parietal bone thickness.
      Twelve fresh human cadaver heads were used for the validation study. To evaluate
      impact resistance, we developed a pendulum Charpy impact testing machine. The
      impact force was gradually increased until failure (fracture) of the defined
      parietal bone area. According to the protocol, we measured the maximum absorbable
      energy or impact force to failure. With our test setup, measurement of the impact
      resistance of parietal bone was accurate to within 0.025 J. We defined a range of
      values and particularly a threshold value. The initial maximal impact must not to
      exceed 4 J. For more accuracy, we compared 5 nondestructive measurement methods
      using a surgical navigation system with optoelectronic tracking. We achieved an
      algorithm based on 2 methods that ensured a measurement resolution of 0.1 mm.
      Validation of this protocol will allow us to evaluate the loss of strength
      resulting from bone removal and the correlation between strength and thickness of
      the parietal bone.

PMID- 21187768
TI  - Endoscopic changes in the upper airway after mandibular distraction osteogenesis.
AB  - INTRODUCTION: Children with micrognathia secondary to craniofacial disorders can
      experience significant airway and feeding difficulties. Mandibular distraction
      osteogenesis (MDO) is one treatment of severe micrognathia. We examined
      endoscopic images for upper airway (UA) soft tissue changes after MDO. We
      hypothesized that MDO produces consistent changes in UA soft tissue, which
      correlate with symptom resolution. MATERIALS AND METHODS: This retrospective
      chart review included 16 patients undergoing MDO from 2002 to 2007. Demographic
      data, symptom information, and preoperative and early and late postoperative
      endoscopic images were collected. Blinded randomized images of UA soft tissues
      were quantitatively analyzed using ImageJ. To compare nonstandardized images,
      ratios of UA dimensions were made. Preoperative and early and late postoperative
      ratios were statistically analyzed with Student's t-test. RESULTS: Sixteen
      patients with a mean age of 237 days were included. Mean distance distracted was
      12 mm. There were significant changes in relative dimensions of the supraglottic
      space in the early postoperative period, which were not maintained in the late
      postoperative period. Nevertheless, all experienced complete relief of airway
      obstruction. DISCUSSION: Our study showed a significant increase in supraglottic
      space dimensions after MDO that was not maintained over time. This is likely
      because of the limitation of images and measurement methods. Despite this,
      significant clinical improvement was seen in all patients, with resolution of
      airway obstruction. This suggests supraglottic changes as well as tongue base
      alterations are related to clinical improvement. Further investigation of
      alterations in UA after MDO is needed to continue characterizing these changes.

PMID- 21187769
TI  - A method for visualizing high-density porous polyethylene (medpor, porex) with
      computed tomographic scanning.
AB  - BACKGROUND: Medpor (Porex Surgical, Inc, Newnan, GA) is composed of porous
      polyethylene and is commonly used in craniofacial reconstruction. When
      complications such as seroma or abscess formation arise, diagnostic modalities
      are limited because Medpor is radiolucent on conventional radiologic studies.
      This poses a problem in situations where imaging is necessary to distinguish the
      implant from surrounding tissues. OBJECTIVE: To present a clinically useful
      method for imaging Medpor with conventional computed tomographic (CT) scanning.
      MATERIALS AND METHODS: Eleven patients (12 total implants) who have undergone
      reconstructive surgery with Medpor were included in the study. A retrospective
      review of CT scans done between 1 and 16 months postoperatively was performed
      using 3 distinct CT window settings. Measurements of implant dimensions and
      Hounsfield units were recorded and qualitatively assessed. RESULTS: Of the 3
      distinct window settings studied, namely, "bone" (W1100/L450), "soft tissue";
      (W500/L50), and "implant" (W800/L200), the implant window proved the most ideal,
      allowing the investigators to visualize and evaluate Medpor in all cases.
      Qualitative analysis revealed that Medpor implants were able to be distinguished
      from surrounding tissue in both the implant and soft tissue windows, with a
      density falling between that of fat and fluid. In 1 case, Medpor could not be
      visualized in the soft tissue window, although it could be visualized in the
      implant window. Quantitative analysis demonstrated a mean (SD) density of -38.7
      (7.4) Hounsfield units. CONCLUSIONS: Medpor may be optimally visualized on
      conventional CT scans using the implant window settings W800/L200, which can aid
      in imaging Medpor and diagnosing implant-related complications.

PMID- 21187770
TI  - High alpha-defensin and S100A7 expression and missing DOC-1 down-regulation
      characterize irritation fibromas of the oral cavity and may counteract malignant
      transformation.
AB  - PURPOSE: The purposes of this study were to analyze the gene expression pattern
      of antimicrobial peptides, tumor suppressors, growth factors, matrix
      metalloproteases, and inflammatory cytokines and chemokines in oral irritation
      fibromas and to identify genes with protective effects against malignant
      transformation in benign proliferating tumors of the oral mucosa. MATERIALS AND
      METHODS: Biopsies of irritation fibromas (n = 15) and healthy gingiva (n = 15)
      were obtained during routine surgical procedures. RNA was extracted according to
      standard protocols, and transcription levels of CCL20, DEFA 1/3, DEFA 4, S100A7,
      DOC-1, interleukin (IL) 1beta, IL-6, IL-8, IL-10, tumor necrosis factor alpha,
      Cox-2, matrix metalloproteinase 1 (MMP-1), MMP-2, MMP-3, MMP-8, MMP-9,
      transforming growth factor beta1, transforming growth factor alpha, and
      keratinocyte growth factor were analyzed by real-time polymerase chain reaction.
      In addition, immunostaining was performed to visualize the transcription products
      of the genes of interest in fibroma tissue as well as in healthy gingiva.
      RESULTS: The gene expression of S100A7 was 11.3-fold and that of DEFA 1/3 was 14
      fold higher in irritation fibromas than in healthy gingiva, whereas the
      expression of MMP-3 and of inflammation markers IL-1beta, IL-6, IL-8, tumor
      necrosis factor alpha, and Cox-2 was reduced. Profound down-regulation of DOC-1
      gene expression, characteristic for proliferating malignant tumors of the oral
      cavity, was in irritation fibromas not verifiable. CONCLUSIONS: Changes in the
      expression pattern of S100A7, DEFA 1/3, and MMP-3 seem to be involved in the
      development of irritation fibromas, whereas chronic inflammation might be of less
      importance. Overexpression of S100A7, but missing down-regulation of the tumor
      suppressor gene DOC-1, might exert protective effects and counteract malignant
      transformation of benign, proliferating lesions of the oral cavity.

PMID- 21187771
TI  - Distraction osteogenesis with pivot plate in the treatment of scaphocephaly.
AB  - In scaphocephaly, traditional distraction osteogenesis increases only the
      bitemporal width. We describe distraction osteogenesis with a pivot plate for
      scaphocephaly, which not only increases the bitemporal width but also decreases
      the anteroposterior length. Three patients with scaphocephaly were treated using
      distraction osteogenesis with a pivot plate between January 2005 and June 2006.
      These children underwent cranial reshaping by gradual distraction using an
      external distraction device and pivot plate. The distraction rate was 1 mm/d, and
      the latency period was 5 days. The follow-up period after distraction
      osteogenesis ranged from 16 to 24 months. No specific complications, such as
      accidental removal of the distraction devices, infection, or neurologic problems
      in any patient, occurred. The mean distraction was 45 mm. The mean cranial index
      was 73.6. Distraction osteogenesis for scaphocephaly is still in the development
      stage, but it is becoming accepted as a useful method because of its many
      advantages. Distraction osteogenesis with a pivot plate for scaphocephaly is
      better than other distraction osteogenesis techniques because it induces
      increased bitemporal width and decreased anteroposterior length synchronously.

PMID- 21187772
TI  - Increased incidence of metopic suture abnormalities in children with positional
      plagiocephaly.
AB  - Metopic craniosynostosis has traditionally been reported to be the third most
      common form of single-suture synostosis. The purposes of this article were to
      analyze the relationship between metopic craniosynostosis and positional
      plagiocephaly and to define more clearly the differences between the changes seen
      with true suture fusion compared with metopic abnormalities secondary to
      positional changes. This is an institutional review board-approved retrospective
      review of three-dimensional computed tomographic scans for abnormalities of the
      metopic suture in all children treated at our institution for positional
      plagiocephaly between 1997 and 2007. We also independently reviewed the images of
      all patients treated for metopic synostosis for evidence of positional
      plagiocephaly during the same period. Among the positional plagiocephaly group,
      39% were noted to have some form of metopic suture abnormality. Of the children
      treated for metopic craniosynostosis, a much smaller percentage also was noted to
      have evidence of positional plagiocephaly. Between 1997 and 2007, we treated 93
      patients (50%) for sagittal synostosis, 41 patients (22%) for unicoronal, 41
      patients (22%) for metopic, 4 patients (2%) for lamdoid, and 7 patients (4%) with
      multiple-suture involvement. This study demonstrates an increasing trend toward
      metopic suture abnormalities during the past 10 years, which corresponds to the
      same time interval of an increased incidence of positional abnormalities. It is
      postulated that some of these abnormalities are related to deformational forces
      resulting from posterior pressure. Altered mechanical forces from supine infant
      positioning may be associated with early metopic suture ridging and dysmorphology
      distinct from true craniosynostosis.

PMID- 21187773
TI  - Capsule formation can make secondary reconstruction of the dura mater unnecessary
      after cranial infection.
AB  - PURPOSE: Defects of the dura mater caused by surgical intervention are often
      reconstructed using artificial substitutes such as polytetrafluoroethylene
      membrane (Gore-Tex in commercial name). In cases where secondary infection
      develops after the initial operation, the artificial substitute used in the
      primary surgery needs to be removed, and the cranial defect should be covered
      with tissues abundant in blood supply. The present study discusses the necessity
      of secondary reconstruction of the dural defect in the recovery operation.
      METHODS: A retrospective study was conducted on 12 patients in whom artificial
      substitute was exposed because of necrosis of the overlying tissues due to
      infection or radiation. In recovery operations, the artificial substitute was
      removed, and the conditions of the underlying defects were evaluated. RESULTS: In
      all cases, capsule formation had developed to cover dural defects underneath the
      infected artificial substitutes. The capsules were transparent and watertight,
      presenting no leakage of cerebrospinal fluid. After coverage of the defect
      regions using free-flap transfer, no patient developed postoperative
      complications in follow-up periods of at least 6 months. CONCLUSIONS: Capsule
      formation occurs under artificial substitutes after replacement of the dura
      mater. Because the capsules retain the cerebrospinal fluid, replacement of the
      artificial materials is unnecessary in the secondary operation.

PMID- 21187774
TI  - Influence of metopic suture fusion associated with sagittal synostosis.
AB  - Some patients with sagittal synostosis present with a fused metopic suture. We
      hypothesize that premature metopic suture fusion consistently and identifiably
      alters form associated with sagittal synostosis. We previously validated three
      dimensional vector analysis as a tool for the study of cranial morphology and
      used it herein to distinguish between dysmorphologies of isolated sagittal
      synostosis (ISS) and combined sagittal-metopic synostosis (CSM). Preoperative
      computed tomographic scans for patients with ISS and CSM were compared with
      matched normative counterparts. Premature metopic suture fusion was defined by
      established radiographic criteria. Color-coded point clouds were created for each
      scan, with color gradient based on patient deviation from normal across the
      dysmorphic skull. Standard deviation data were evaluated in 7 cranial regions and
      compared between ISS and CSM. Mean ISS and CSM point clouds were evaluated. Using
      three-dimensional vector analysis, standard anthropometric data/indices were
      determined and compared between the 2 groups. Differences in ISS and CSM regional
      deviations and index measurements were not statistically significant. Mean ISS
      and CSM representations depicted similar overall morphology. Using accepted
      criteria for identification of metopic synostosis in CSM, only subtle differences
      appear between the 2 populations on average. Expected morphologic changes
      associated with metopic synostosis are present in only a small number of patients
      with CSM, arguing against our hypothesis, and calling into question the criteria
      used to identify premature metopic suture fusion. Normal metopic suture fusion
      occurs for a continuum of time. Our findings suggest that the normal continuum
      may begin earlier than the literature suggests. In the setting of sagittal
      synostosis, the influence of metopic suture fusion and treatment is best
      determined by individual morphologic analysis.

PMID- 21187775
TI  - Accurate facial morphologic measurements using a 3-camera photogrammetric method.
AB  - OBJECTIVES: A new, low-cost photogrammetric method has been developed for facial
      morphometry applications. To evaluate the system, tests for the measurement and
      comparison of three-dimensional virtual faces were carried out in different
      subjects. MATERIALS AND METHODS: Twenty adult white Italian subjects, 10 men and
      10 women, of ages ranging from 23 to 37 years, were included in this study. Three
      cameras were finely calibrated, and the point precision vector length was
      calculated, together with the quality parameters. For each subject, 3 different
      acquisitions were performed. A tessellated surface was obtained from each point
      cloud. The comparison was made by aligning three-dimensional information from
      different models. Differences between 2 different models were estimated by
      analysis of the distances. RESULTS: For the cases analyzed, the mean point
      precision overall root-mean-square vector length was 0.07 mm, with a SD of 0.027
      mm. The results are reported for the system's capability of discriminating
      between the faces of different people. Results of comparisons between facial
      models of a single person were compared with those of comparisons between
      different subjects. Student's t-test revealed that the system was able to
      discriminate among different people, with a P > 95%. Two sex subgroups were
      formed: the mean error between subgroups ranged from 1.65 to 3.43 mm, and the
      mean ranged from 1.76 to 2.72 mm. CONCLUSIONS: The experiments confirmed the
      capabilities and the accuracy of the proposed photogrammetric system. Facial
      comparison was performed by analysis of distances on three-dimensional virtual
      models.

PMID- 21187776
TI  - Parasagittal suture after strip craniectomy.
AB  - BACKGROUND: Suture reformation after strip craniectomy for nonsyndromic sagittal
      synostosis remains an inconsistent and underreported phenomenon. Although several
      theories have been proposed to account for the fate of the cranial defect, no
      explanation accurately matches clinical experience with the appearance of
      reformed sutures, ectopic sutures, and complete defect ossification
      postoperatively. METHODS AND RESULTS: We review the case of a 7-year-old boy who
      formed a parasagittal suture at the defect margin after strip craniectomy for
      nonsyndromic sagittal synostosis. We review the literature and the clinical
      experiences of previous authors. CONCLUSIONS: The pathogenesis of suture
      reformation and the biomechanical forces shaping suture formation are still
      poorly understood. Previous reports of postoperative suture reformation offer
      inconclusive evidence as to whether a pathologic suture, an abnormal cranial
      base, or a combination of biomechanical forces plays the larger role. It remains
      an open question as to whether a single underlying mechanism can explain suture
      reformation or if there are instead multiple causes.

PMID- 21187777
TI  - Quantification of facial movements by surface laser scanning.
AB  - Quantification of facial mimic ability represents a need for comparative
      investigation in facial medicine and surgery. The aim of the current study was to
      develop a simple, noninvasive, repeatable three-dimensional method for measuring
      facial mobility in clinical and research setup. The faces of 20 healthy adult
      subjects (10 men and 10 women) and 12 primary school children (6 boys and 6
      girls), without craniofacial pathologic injuries or previous treatments, were
      captured by a Cyberware 3030RGB laser scanner (Cyberware, Inc, Monterey, CA) in
      rest position and during voluntary movements. Data were processed by Cyberware
      Echo (Cyberware, Inc) and Inus Rapidform 2004 software (INUS Technologies Inc,
      Seoul, South Korea). Each movement was assigned a main landmark. The facial
      movements were described for surface displacement using clearance vector mapping
      and three-dimensional tracing of the skin landmarks. The mean landmark
      displacement vector was also calculated for every movement. The study showed that
      movements were characterized by similar displacement in the same facial areas in
      all subjects. Minor differences were recorded between adult subjects and
      children. Descriptive statistics concerning the amount and direction of movements
      were provided. A case of unilateral postsurgical nerve palsy was prospectively
      analyzed to test applicability of the method in clinical investigation. A
      numerical scale based on the mean movements was constructed and used to monitor
      recovery of function.The method developed seems easy, noncontact, and effective
      to quantify facial movements in normal and pathologic conditions. It may be
      usefully applied to the investigation and the clinical monitoring of different
      medical and surgical pathologic conditions.

PMID- 21187778
TI  - Evaluation of metal concentrations in hair and nail after orthognathic surgery.
AB  - INTRODUCTION: Titanium miniplates are widely used in orthognathic surgery.
      Titanium is considered to be a bioinert material, although its long-term
      accumulation in distant human tissues is unclear. The study was designed to
      evaluate the concentrations of aluminum (Al), titanium (Ti), and vanadium (V) in
      the hair and nail of patients who underwent orthognathic surgery. METHODS: The
      study group comprised 20 patients who had had orthognathic surgery minimum 14 and
      maximum 96 months previously (mean [SD], 54.7 [3.5] mo). Miniplates and
      miniscrews were made of Ti-6Al-4V alloys (Trimed, Ankara, Turkey). The control
      group comprised 10 healthy adults not operated on. Metal concentrations in the
      hair and nail of the subjects were measured by inductively coupled plasma mass
      spectroscope (Thermo Elemental X7 series; Thermo Electron, London, England).
      Descriptive statistical methods were used for data analysis, and Mann-Whitney
      test was used to compare both groups. RESULTS: Concentrations of Al, Ti, and V in
      the hair of the study group were significantly higher than those in the control
      group (P < 0.001). Nail Ti and V concentrations of the study group were also
      significantly higher than those of the control group (P < 0.001 and P < 0.01,
      respectively). Nail Al concentration was similar in both groups (P > 0.05).
      CONCLUSIONS: Increased corrosive element concentrations may be observed in the
      hair and nail of patients who underwent orthognathic surgery.

PMID- 21187779
TI  - Assessment of the oral and maxillofacial surgery service in a teaching hospital
      in Brazil.
AB  - OBJECTIVE: The purpose of this study was to determine an epidemiologic profile of
      the patients hospitalized and/or operated on by an oral and maxillofacial surgery
      service in Brazil. MATERIALS AND METHODS: A retrospective and descriptive
      epidemiologic survey of the Oral and Maxillofacial Surgery Service from Saint
      Lucas Hospital at the Pontifical Catholic University, Porto Alegre, Brazil, from
      January 2000 to December 2005, was performed. Data related to the number, sex,
      age, service year, as well as surgical modalities performed, instituted
      treatments, and length of stay, were collected from the hospital's handbooks.
      RESULTS: A total of 1117 patients were attended during the 6 years of study, with
      a decreasing tendency throughout the years (P = 0.022). There was female
      predominance (54%), between 10 and 40 years old, and attended via public health
      system (56%). Among surgical modalities performed, dentoalveolar surgery was the
      most prevalent (22.9%), followed by the orthognathic surgeries (21.4%), facial
      fractures (18%), pathologic condition surgeries (16.7%), and dental implants and
      grafts (13.7%). Surgeries of patients with cleft lip and/or palate (3.4%),
      treatment of maxillofacial infections (2.95%), and temporomandibular joint
      surgeries (1%) were less frequent. CONCLUSIONS: The information presented in this
      research elicited data to clarify the type of attendance performed by the
      service, being a cornerstone for planning, organization, and attention
      improvement of these patients. In addition, this information can compare with
      data among services, specialty acting fields, as well as, its impact in hospital
      activities.

PMID- 21187780
TI  - Classification and pathogenic models of unintentional postural cranial
      deformities in infants: plagiocephalies and brachycephalies.
AB  - Unintentional postural deformities of the skull have increased in a
      pseudoepidemic manner in the last 15 years. Although dorsal decubitus and
      prenatal risk factors can play a role in the genesis of such deformities, we
      think that a crucial determinant is a postnatal defect of cervical mobility
      responsible for the infant's posture (ie, positional preference) when supine.
      Indeed, muscular factors, which limit the range of head and neck movements, have
      been underestimated in the genesis of skull deformities. Here, we have
      retrospectively analyzed data from 181 infants with unintentional skull
      deformities and propose a classification of these deformities into 3 types based
      on their pathogenic model and clinical appearance: fronto-occipital
      plagiocephalies due to severe muscle hypertonia in which the myogenic component
      is the first implicated, occipital plagiocephalies with muscle imbalance due to
      neurogenic muscle hypertonia, and posterior brachycephalies with neurogenic
      muscle hypertonia of the suboccipital muscles due to trauma to the
      occipitovertebral junction. Future studies on the size and density of specific
      muscles or group of muscles should help us to better understand their involvement
      in the pathogenesis of postural deformities. Our findings also highlight the
      importance of carefully assessing cervical mobility during the first week of life
      to detect possible limitations and to prescribe (if needed) an adapted
      rehabilitation. Rehabilitation should be associated with postural measures put in
      place when infants sleep supine to prevent the appearance of skull deformations.

PMID- 21187781
TI  - Treatment of scaphocephaly with combined vertex craniectomy and bilateral
      microbarrel staving.
AB  - INTRODUCTION AND BACKGROUND: Surgical techniques for the treatment of
      scaphocephaly continue to evolve; however, there is still no accepted criterion
      standard. Until recently, the Alder Hey supraregional craniofacial department's
      experience was principally with combined wide-vertex suturectomy and biparietal
      barrel stave osteotomies. AIMS AND OBJECTIVES: To determine whether the technique
      of wide-vertex suturectomy and biparietal barrel stave osteotomies improves the
      cephalic index (CI) in scaphocephalic patients and determine whether age at
      surgery influences outcomes. PATIENTS AND METHODS: A literature review was
      undertaken to confirm recognized outcome measures. Patients who had surgery
      between 2000 and 2006 were enrolled in the audit. Prospective database review
      allowed preoperative and postoperative data collection at 6 weeks, 6 months, and
      2 years. Statistical analysis was performed with Statview V.5.0.1 (Adept
      Scientific, Letchworth, UK). RESULTS: Of 73 children referred to the unit with
      scaphocephaly, 66 underwent surgery. Of these 66 children, 54 were boys and 12
      girls. Mean age at surgery was 11.1 months, with a mode of 6 months and a median
      of 8 months (range, 4-56 mo). Mean change in CI from the preoperative value was
      significant at 6 weeks (P < 0.0001) and 6 months (P < 0.0001) after surgery.
      Early correction of scaphocephaly (<= 9 mo) was associated with a normal CI at 6
      weeks after surgery (P = 0.03). CONCLUSIONS: Wide-vertex suturectomy with
      biparietal barrel stave osteotomies are effective at increasing the CI in
      children with scaphocephaly. Early correction is associated with an improved CI
      in the short term, but long-term outcomes are unclear and require further follow
      up studies.

PMID- 21187782
TI  - Deformational plagiocephaly, brachycephaly, and scaphocephaly. Part II:
      prevention and treatment.
AB  - Cranial deformation is the most common cause of abnormal head shape. Intentional
      and unintentional alterations of cranial form are associated with the application
      of external pressure to the growing infant head, and such changes have been
      recorded throughout man's history. Recent changes in Western sleeping practices,
      instituted to reduce the incidence of sudden infant death syndrome, have led to a
      dramatic rise in cranial deformation and renewed interest in this subject. This 2
      part review presents a pragmatic clinical approach to this topic including a
      critical review of the literature as it applies to each aspect of this common
      diagnosis: historical perspective, terminology, differential diagnosis,
      etiopathogenesis and predisposing factors, and prevention and treatment.

PMID- 21187783
TI  - Deformational plagiocephaly, brachycephaly, and scaphocephaly. Part I:
      terminology, diagnosis, and etiopathogenesis.
AB  - Cranial deformation is the most common cause of abnormal head shape. Intentional
      and unintentional alterations of cranial form are associated with the application
      of external pressure to the growing infant head, and such changes have been
      recorded throughout man's history. Recent changes in Western sleeping practices,
      instituted to reduce the incidence of sudden infant death syndrome, have led to a
      dramatic rise in the incidence of cranial deformation and renewed interest in
      this subject. This 2-part review presents a pragmatic clinical approach to this
      topic including a critical review of the literature as it applies to each aspect
      of this common diagnosis: historical perspective, terminology, differential
      diagnosis, etiopathogenesis and predisposing factors, and prevention and
      treatment.

PMID- 21187784
TI  - An epidemiological study of nonsyndromal craniosynostoses.
AB  - OBJECTIVE: To compare our data with recent studies that have suggested a change
      in the distribution of the forms of nonsyndromal synostosis in the clinical
      population, we conducted a retrospective analysis of the diagnoses of children
      with isolated synostosis examined at a large craniofacial center between 1987 and
      2009. This also included the range of nonsyndromal multisuture synostoses.
      DESIGN: A retrospective chart review of all preoperative patients with
      nonsyndromal synostosis seen between 1987 and 2009 was performed. Only patients
      with a radiologically confirmed craniosynostosis were included. Data on patients'
      sex and laterality in unilateral synostoses were collected. Two temporally
      distinct subgroups (1996-2000 and 2005-2009) were defined to evaluate changes in
      the distribution of the most common forms of isolated craniosynostosis using the
      Fisher exact test. RESULTS: A total of 690 patients met the inclusion criteria.
      The largest group of patients had sagittal synostosis, with metopic synostosis as
      the second most common diagnosis, representing one-fourth of the patients,
      followed closely by unilateral coronal synostosis. All other synostoses
      encompassed one-eighth of the group. Patients with sagittal or metopic synostosis
      were overwhelmingly male, whereas those with unilateral coronal synostosis were
      predominantly female. Patients with unilateral synostoses were affected primarily
      at the right suture. CONCLUSIONS: Data from our patients indicate a much higher
      incidence of metopic synostosis than has been reported in the traditional
      clinical literature but is consistent with recent published data. The causes of
      this are unclear at this point, but the Fisher exact test excludes an increase in
      the frequency of metopic synostosis. Improved clinical diagnosis or ascertainment
      bias remains a possibility. Further research is needed to elucidate the answer to
      this question. Our data also indicate the occurrence of a small number of rare
      multisuture synostoses of unknown origin.

PMID- 21187785
TI  - Quality of life in adolescents with autism spectrum disorders: reliability and
      validity of self-reports.
AB  - PURPOSE: This study examined the reliability and validity of self-reported
      quality of life (QoL) among adolescents with autism spectrum disorders (ASDs) but
      without mental retardation (IQ >70) using a validated QoL measure, Pediatric
      Quality of Life Inventory. Secondarily, the self-reported QoL of adolescents with
      ASDs was compared with published normative data. METHODS: Thirty-nine adolescents
      with ASDs and their parents completed a QoL instrument and brief measures of
      psychosocial distress and self-esteem. A screening test of cognitive abilities
      was administered to adolescents; parents completed an assessment of behavioral
      and emotional symptoms and an assessment of the presence and extent of autistic
      social impairments. RESULTS: Adolescent self-reports of QoL demonstrated internal
      reliability and concurrent validity. Self-reports on the Pediatric Quality of
      Life Inventory demonstrated moderate to large positive correlations with a
      measure of self-esteem and moderate to large negative correlations with measures
      of anxiety and mood. Concurrent validity with parent proxy reports fell within
      the range of expected values based on past studies of inter-rater reliability for
      QoL, with parents of adolescents reporting lower QoL when compared with
      adolescent reports. Adolescents reported QoL below the population mean for all
      domains. CONCLUSIONS: Results of this study provide preliminary evidence that
      adolescents with ASDs are able to report on their own QoL in a valid and reliable
      manner. Based on our findings, the measurement of QoL may be useful for clinical
      care and research about adolescents with ASDs.

PMID- 21187786
TI  - The impact of weight gain or loss on health care costs for employees at the
      Johnson & Johnson Family of Companies.
AB  - OBJECTIVE: To quantify the impact of weight gain or weight loss on health care
      costs. METHODS: Employees completing at least two health risk assessments during
      2002 to 2008 were classified as adding, losing, or staying at high/low risk for
      each of the nine health risks including overweight and obesity. Models for each
      risk were used to compare cost trends by controlling for employee
      characteristics. RESULTS: Employees who developed high risk for obesity (n = 405)
      experienced 9.9% points higher annual cost increases (95% confidence interval:
      3.0%-16.8%) than those who remained at lower risk (n = 8015). Employees who moved
      from high to lower risk for obesity (n = 384), experienced annual cost increases
      that were 2.3% points lower (95% confidence interval: -7.4% to 2.8%) than those
      who remained high risk (n = 1699). CONCLUSIONS: Preventing weight gain through
      effective employee health promotion programs is likely to result in cost savings
      for employers.

PMID- 21187787
TI  - Productivity and health: an application of three perspectives to measuring
      productivity.
AB  - OBJECTIVE: The objective of the study was to illustrate the meaningful
      relationship between self-reported measures of productivity and health status
      from three different perspectives. METHODS: Health risk data was drawn from
      577,186 individuals who completed the HealthMedia Succeed Health Risk Assessment
      and the Work Productivity and Activity Impairment questionnaire over a span of
      nearly four years. Analyses were conducted for 10 modifiable health risks and
      five chronic conditions. RESULTS: Productivity impairment was greater for high
      risk participants for the modifiable health risks and those who had been
      diagnosed with a chronic condition. Improvements in health status led to
      significant gains in productivity. Modifiable health risks are nearly five times
      more costly than chronic conditions. CONCLUSIONS: The value in a self-report
      measurement approach to productivity was demonstrated by illustrating the
      meaningful relationships between health status and productivity as measured by
      the Work Productivity and Activity Impairment.

PMID- 21187788
TI  - The direct and indirect cost burden of acute coronary syndrome.
AB  - OBJECTIVE: Quantify the incremental health care costs and workplace absence and
      short-term disability costs, to payers and employers, of patients hospitalized
      for acute coronary syndrome (ACS). METHODS: Retrospective study using medical
      insurance claims for the years 2002 to 2007. Patients were aged 18 to 64 years
      and hospitalized for ACS between January 1, 2003, and December 31, 2006;
      comparison patients without evidence of coronary artery disease were also
      selected. The incremental impact of ACS was estimated using weighted regression.
      RESULTS: 30,200 ACS patients were selected. Incremental annual direct costs of
      ACS were $40,671 (P < 0.001). For the indirect cost sub-analyses, incremental
      short-term disability costs of ACS were $999 (P < 0.001) and incremental absence
      costs were insignificant (P = 0.314) but from a small sample (N = 416).
      CONCLUSIONS: Patients with ACS impose a substantial direct cost burden on
      employers and payers and a substantial indirect cost burden on employers. Acute
      coronary syndrome is more costly to employers and payers than other health
      conditions that are common among employed persons. Rehospitalizations after the
      initial hospitalization are common and represent a large portion of the cost.

PMID- 21187789
TI  - Comorbidity and labor force activity among people with psychiatric disorders.
AB  - OBJECTIVE: Comorbidity among people with psychiatric disorders with respect to
      other health conditions is extensive yet is rarely explored in-depth in
      occupational studies. We investigated how other ICD-10 comorbidity impacted on
      the labor force activity of people with psychiatric disorders. METHODS: A
      secondary analysis of data files was conducted provided by the Australian Bureau
      of Statistics (ABS) from a 2003 population survey (N = 36,088). The reference
      group was working age community residents without long-term health conditions.
      RESULTS: Comorbidity with a broad range of ICD-10 health conditions can be
      characterized by both type and extent of comorbidity. Both dimensions are needed
      to explain impacts on labor force activity. CONCLUSIONS: Health professionals,
      policymakers, and administrators can utilize these results to identify people
      with psychiatric disorders and comorbidity profiles most likely to need more
      intensive vocational services.

PMID- 21187790
TI  - Respiratory symptoms were associated with lower spirometry results during the
      first examination of WTC responders.
AB  - OBJECTIVE: Determine if World Trade Center (WTC) disaster responders had lower
      lung function and higher bronchodilator responsiveness than those with
      respiratory symptoms and conditions. METHODS: We evaluated cardinal respiratory
      symptoms (dyspnea, wheezing, dry cough, productive cough) and determined the
      difference in FEV1, FVC, and bronchodilator responsiveness. RESULTS: All
      respiratory symptoms were associated with a lower FEV1 and FVC, and a larger
      bronchodilator response. Responders reporting chronic productive cough, starting
      during WTC work and persisting, had a mean FEV1 109 mL lower than those without
      chronic persistent cough; their odds of having abnormally low FEV1 was 1.40 times
      higher; and they were 1.65 times as likely to demonstrate bronchodilator
      responsiveness. CONCLUSIONS: Responders reporting chronic persistent cough,
      wheezing or dyspnea at first medical examination were more likely to have lower
      lung function and bronchodilator responsiveness.

PMID- 21187791
TI  - Workplace violence: prevalence and risk factors in the safe at work study.
AB  - OBJECTIVE: Nurses face one of the highest rates of reported workplace violence
      (WPV). This research examined the prevalence of WPV and demographic, work
      related, and adult and childhood abuse histories as risk factors for WPV among
      2166 nurses/nursing personnel across four health care institutions in one US
      metropolitan area. METHODS: Using data from an online cross-sectional survey,
      multivariate logistic regression was utilized to determine risk factors for
      physical and psychological WPV. RESULTS: Almost one-third (30%) of nurses/nursing
      personnel experienced WPV (19.4% physical, 19.9% psychological). Risk factors
      included being a nurse, white, male, working in the emergency department, older
      age, longer employment, childhood abuse, and intimate partner violence.
      CONCLUSIONS: Adult and childhood abuse histories have not been considered in
      previous large-scale investigations, but were significant risk factors along with
      other previously identified risk factors for WPV.

PMID- 21187792
TI  - Cost burden of the presenteeism health outcome: diverse workforce of nurses and
      pharmacists.
AB  - OBJECTIVES: To describe presenteeism, its cost burden, and comparative and
      interactive effects of race/ethnicity in nurses and pharmacists. METHODS: Using
      226 self-reports, ordinal logistic regression with marginal/interactive effects
      modeled 12 presenteeism predictors, contingency tables detected
      differences/associations, and Human Capital Approach determined cost burden.
      RESULTS: Presenteeism's prevalence was 52.65% with mean productivity decrement
      13.2%. Minorities had lower base presenteeism rates; however, race/ethnicity
      differences were not significant. Physical symptoms and mental conditions were
      associated with increased presenteeism likelihood, while decreased likelihood was
      associated with no medications or lack of resumption of previous medications.
      Indirect cost burden in 2008 averaged $12,605 per professional for $36 billion
      nationally. CONCLUSIONS: Prevention of symptoms and conditions impacting
      cognitions, pain, and perceptions can decrease presenteeism. Minorities' lower
      rates of presenteeism can be viewed both positively and negatively.

PMID- 21187793
TI  - Acute decrease in HDL cholesterol associated with exposure to welding fumes.
AB  - OBJECTIVE: To investigate acute changes in circulating lipids after exposure to
      relatively high levels of particulate matter through welding. METHODS: Using a
      repeated measures panel study, lipid levels before and after welding and personal
      exposures to fine particulate matter (PM2.5) were measured in 36 male welders
      over 63 exposure and/or control days. RESULTS: There was a trend toward decrease
      in HDL (-2.3 mg/dL, P = 0.08) 18 hours after welding. This effect became
      significant (-2.6 mg/dL, P = 0.05) after adjustment for possible confounders. The
      effect was strongest (-4.3 mg/dL, P = 0.02) among welders who did not weld the
      day before the study. There were no significant changes in other lipids
      associated with welding or PM2.5 exposure. CONCLUSION: Welding exposure was
      associated with an acute decrease in circulating HDL, which may relate to the
      inflammatory and proatherosclerotic effects of fine particle exposure.

PMID- 21187794
TI  - Assessing the impact of migraine onset on work productivity.
AB  - OBJECTIVE: Examine the impact of migraine on work productivity, and particularly
      the association between time of migraine onset and lost productivity as measured
      by absenteeism and presenteeism. METHODS: A total of 509 people with migraine
      completed one online baseline survey and a diary survey after each of their next
      three migraines. All subjects were 18 or older and employed full time. RESULTS:
      Sixty-four percent of migraines occurred on a workday. Of these, 68% resulted in
      some work productivity impact in the form of absenteeism or presenteeism.
      Migraines occurring during usual sleeping hours or prior to the start of work had
      the greatest impact on productivity. CONCLUSIONS: Findings indicate that
      absenteeism and presenteeism are both substantial contributors to work
      productivity loss. Primary factors associated with lost productivity include pain
      severity, migraine symptoms, and sleep disturbance.

PMID- 21187795
TI  - Why are financial incentives not effective at influencing some smokers to quit?
      Results of a process evaluation of a worksite trial assessing the efficacy of
      financial incentives for smoking cessation.
AB  - OBJECTIVE: Process evaluation of a worksite intervention in which employees were
      offered $750 to complete a cessation program and to quit smoking. METHODS:
      Awareness and attitudes about financial incentives were assessed following a
      randomized controlled trial of 878 smokers at a US-based company. RESULTS:
      Cessation program attendance was higher in incentive group versus control (20.2%
      vs 7.1%, P < 0.01). Most quitters (69.8%) in the incentive group who were already
      motivated to quit and reported that they would have quit for less money, said
      incentives were "not at all" or only "somewhat" important. Most nonquitters in
      the incentive group reported that even $1500 would not have motivated them to
      quit. CONCLUSIONS: Financial incentives are ineffective at motivating some
      smokers to quit. Internal motivation and readiness to quit need to be
      sufficiently high for relatively modest incentives to be effective.

PMID- 21187796
TI  - Nasal and ocular effects in foundry workers using the hot box method.
AB  - OBJECTIVE: To investigate the prevalence of nasal and ocular symptoms and nasal
      signs in foundry workers exposed to monoisocyanates using the Hot Box method.
      METHODS: Forty-three foundry workers and 69 referents completed questionnaires
      and were examined by a rhinologist. Exposure to isocyanic acid, methyl
      isocyanate, formaldehyde, and total dust was measured. RESULTS: Nasal symptoms
      and signs were associated with exposure, and dose-response relationships between
      nasal symptoms and exposure to isocyanic acid, methyl isocyanate, and
      formaldehyde were observed. Dry nasal mucosa was more prevalent in exposed
      workers than in referents. These findings were not substantially affected by the
      exclusion of asthmatic and allergic individuals, smokers, or females.
      CONCLUSIONS: An increased prevalence of nasal symptoms and signs was observed
      among exposed workers, suggesting an association with the foundry environment
      involving monoisocyanates and other airway irritants, such as formaldehyde and
      dust.

PMID- 21187797
TI  - Organizational climate, occupational stress, and employee mental health:
      mediating effects of organizational efficiency.
AB  - OBJECTIVE: To determine whether the relationship between organizational climate
      and employee mental health is consistent (ie, invariant) or differs across four
      large hospitals, and whether organizational efficiency mediates this
      relationship. METHODS: Participants (total N = 5316) completed validated measures
      of organizational climate variables (social climate, participatory management,
      goal clarity, and performance feedback), organizational efficiency, occupational
      stress, and mental health. RESULTS: Path analysis best supported a model in which
      organizational efficiency partially mediated relationships between organizational
      climate, occupational stress, and mental health. CONCLUSIONS: Focusing on
      improving both the psychosocial work environment and organizational efficiency
      might contribute to decreased employee stress, improved mental well-being, and
      organizational performance.

PMID- 21187798
TI  - Prevalence rates and costs of metabolic syndrome and associated risk factors
      using employees' integrated laboratory data and health care claims.
AB  - OBJECTIVE: This study assessed the relative value of using laboratory, claims, or
      integrated laboratory-claims data to identify prevalence rates and costs of
      metabolic syndrome among Chevron Texaco Corporation, San Ramon, California,
      employees. METHODS: This study identified five metabolic syndrome risk factors by
      using three identification methods: (1) health-screening data, applying the
      National Cholesterol Education Program Adult Treatment Panel III and World Health
      Organization definitions; (2) employer-based claims data applying proxy
      International Classification of Diseases, 9th Revision definitions; and (3)
      integrated laboratory-claims data. Prevalence rates and costs of metabolic
      syndrome and associated risk factors were estimated. RESULTS: Laboratory-defined
      and claims-defined approaches underestimated metabolic syndrome prevalence rates
      compared with the integrated approach by 22.9% and 87.5%, respectively. Employees
      with metabolic syndrome had double the costs of those without any risk factors
      ($4603 vs $1859; P = 0.0384). CONCLUSIONS: Results suggest that integrating
      laboratory and claims data is a more balanced approach than either approach alone
      for identifying metabolic syndrome among Chevron employees.

PMID- 21187799
TI  - Respirator impact on work task performance.
AB  - OBJECTIVE: Respirators are used to maintain work performance and protect against
      inhaled toxins. The study compared the effects of two commonly used respirator
      classes--dual cartridge half face mask (HFM) and filtering face piece (N95)--upon
      work productivity. METHODS: 107 volunteers performed eight simulated work tasks
      when using the HFM and N95 respirators. Tasks included several body positions,
      exertion levels, and concentration requirements. Objective measures of accuracy
      and speed were developed for each task. Scores for each task were based on the
      subject's rank among all subjects. RESULTS: All subjects were capable of
      performing the tasks. There were no statistically significant differences between
      respirator types in either task performance metric. CONCLUSIONS: Productivity
      impact can be measured effectively and should be considered as part of respirator
      design testing and when selecting the optimal respirator for a worker.

PMID- 21187800
TI  - Refractive outcome after severe Pseudomonas aeruginosa Keratitis.
AB  - A 15-year-old myopic female contact lens wearer developed severe central corneal
      keratitis in the left eye caused by Pseudomonas aeruginosa. A rapid diagnosis and
      treatment led to a satisfactory response, although a gray central corneal scar,
      hyperopia, and visual loss remained. No surgery was required after the infection
      resolved, and the patient was assessed annually. Sixty-four months later, the
      cornea was almost totally transparent and she had a visual acuity of 20/20. The
      results of the topographical examination were similar to those after a refractive
      ablative procedure. Satisfactory refractive outcome after severe Pseudomonas
      aeruginosa keratitis may occur in extraordinary cases.

PMID- 21187801
TI  - Risk factors for physical discomfort in Australian optometrists.
AB  - PURPOSE: There are anecdotal reports that optometrists suffer work-related
      physical discomfort but no published reports to support this. METHODS: An on-line
      questionnaire was sent by e-mail to ~1700 Australian optometrists. Participants
      were asked if they experienced work-related discomfort in any of eight nominated
      body regions, the type and severity of discomfort, self-reported work-related
      factors contributing to the discomfort, and demographic and work-related
      information. RESULTS: Four hundred sixteen optometrists participated in the
      questionnaire. Work-related physical discomfort was reported by 82% of
      respondents. The most common sites of discomfort were neck, shoulder, and lower
      back. Univariate analysis revealed that females are more likely to report
      discomfort than males (p = 0.001) and more likely to report a higher number of
      discomfort sites (p = 0.002). Multivariate analysis revealed that females have up
      to a 6.6* [confidence interval (CI) = 2.2-19.9] greater risk of reporting
      discomfort in individual body locations compared with males and a higher risk of
      experiencing severe discomfort (discomfort present for >30 days) [odds ratio (OR)
      = 3.0, CI = 1.7 to 5.5]. A greater number of eye examinations per day increased
      the risk of reporting work-related discomfort by up to 5.1* (CI = 2.1 to 12.7).
      Being self-employed and being older than 40 years both appear to be protective
      factors for work-related discomfort. The risk of experiencing severe discomfort
      is increased by performing repetitive tasks (OR = 1.9, CI = 1.2 to 3.1) and by
      continuing to work while injured (OR = 2.9, CI = 1.6 to 5.2). Eliminating both
      these factors would reduce the disease load for severe discomfort by 28%.
      CONCLUSIONS: Females, young optometrists, and those conducting a high number of
      consultations daily have a higher risk of experiencing work-related physical
      discomfort. Performing repetitive tasks and continuing to work while injured
      increases the risk of severe discomfort. The results of this investigation have
      important implications for the longevity of the optometry workforce.

PMID- 21187803
TI  - In vitro analysis of the physical properties of contact lens blister pack
      solutions.
AB  - PURPOSE: Since the initial development of silicone hydrogels, many modifications
      to the bulk and surface properties of the lenses have been undertaken to improve
      the wettability and comfort of the lenses. Recently, manufacturers have
      incorporated various "wetting agents" or surface-active agents into the blister
      packaging solutions (BPSs) of the lenses to improve initial comfort of the lens
      on eye. The purpose of this study was to measure and compare the pH, surface
      tension (ST), viscosity, and osmolality of BPSs for a variety of silicone
      hydrogel and polyHEMA-based hydrogel lenses. In addition, two saline solutions
      were tested for comparison purposes. METHODS: The pH, osmolality, ST, and
      viscosity were measured for the BPSs for lotrafilcon B and lotrafilcon A and
      lotrafilcon B with a "modified BPS" (m-lotrafilcon A, m-lotrafilcon B) (CIBA
      Vision, Duluth, GA); balafilcon A (Bausch & Lomb, Rochester, NY); galyfilcon A,
      senofilcon A, and narafilcon A (Johnson & Johnson, Jacksonville, FL); and
      comfilcon A and enfilcon A (CooperVision, Pleasanton, CA) and BPSs from two
      conventional polyHEMA-based materials-etafilcon A (Johnson & Johnson) and
      omafilcon A (CooperVision). The two saline solutions tested were Unisol (Alcon,
      Fort Worth, TX) and Softwear Saline (CIBA Vision). RESULTS: The pH results for
      the two saline solutions and all BPSs remained in the pH range of tears (6.6
      7.8). The ST of the modified BPS was significantly lower (p < 0.01) than the
      original non-modified BPS. Viscosity measurements ranged between 0.90 and 1.00 cP
      for all BPSs and saline solutions, except for the modified BPS, which had
      significantly higher viscosities (p < 0.001). Osmolality measurements were not
      significantly different (p > 0.05) between BPSs made by the same manufacturer but
      were significantly different compared with BPSs made by different manufacturers
      (p < 0.05). CONCLUSIONS: The incorporation of wetting agents and surfactants into
      BPSs does alter the physical properties of the BPSs, which may have clinical
      implications regarding initial in-eye comfort.

PMID- 21187802
TI  - Impact of multipurpose solutions released from contact lenses on corneal cells.
AB  - PURPOSE: To assess, in vitro, the effect of the release of contact lens
      multipurpose solutions (MPS) from two silicone hydrogel lenses on human corneal
      epithelial cells. METHODS: A monolayer of immortalized human corneal epithelial
      cells was seeded in a 24-well plate in keratinocyte serum-free medium.
      Lotrafilcon A (LA) and balafilcon A (BA) lenses were placed on top of the
      adherent cells for 8 and 24 h, after being soaked in MPS, borate-buffered
      (Unisol) or phosphate-buffered saline overnight. Cells were assayed for viability
      using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay or
      for alpha3, beta1, and beta4 integrin expression and caspase activation by flow
      cytometry. RESULTS: After 8 h, LA lenses soaked in Unisol, Opti-Free Express
      (OFX), and ReNu MultiPlus (ReNu) showed decrease in cell viability. LA and BA
      soaked in Complete Moisture Plus (Complete) had similar viability at around 85%
      of control. After 24 h, a further decrease in viability was observed with all MPS
      soaked lenses; LA soaked in OFX significantly reduced viability compared with
      Unisol-soaked lenses. In addition, reduced levels of integrin expression for
      lenses soaked in OFX and ReNu, and for BA soaked in Complete were observed. At 24
      h, only LA soaked in OFX led to an increase in caspase activation. CONCLUSIONS:
      Our results indicate an increase in cytotoxicity with borate-based MPS solutions
      in vitro when compared with both phosphate-buffered saline and borate-exposed
      lenses, suggesting that biocides and/or additives play a role in the observed
      cell reaction. Moreover, the mechanism of in vitro solution-induced toxicity
      appeared to be mediated by lens type, suggesting differences in the preferential
      adsorption/release profile of certain compounds.

PMID- 21187804
TI  - Differential diagnosis of lower extremity enlargement in pediatric patients
      referred with a diagnosis of lymphedema.
AB  - BACKGROUND: There are many causes for a large lower limb in the pediatric age
      group. These children are often mislabeled as having lymphedema, and incorrect
      diagnosis can lead to improper treatment. The purpose of this study was to
      determine the differential diagnosis in pediatric patients referred for lower
      extremity "lymphedema" and to clarify management. METHODS: The authors' Vascular
      Anomalies Center database was reviewed between 1999 and 2010 for patients
      referred with a diagnosis of lymphedema of the lower extremity. Records were
      studied to determine the correct cause for the enlarged extremity. Alternative
      diagnoses, sex, age of onset, and imaging studies were also analyzed. RESULTS: A
      referral diagnosis of lower extremity lymphedema was given to 170 children;
      however, the condition was confirmed in only 72.9 percent of patients. Forty-six
      children (27.1 percent) had another disorder: microcystic/macrocystic lymphatic
      malformation (19.6 percent), noneponymous combined vascular malformation (13.0
      percent), capillary malformation (10.9 percent), Klippel-Trenaunay syndrome (10.9
      percent), hemihypertrophy (8.7 percent), posttraumatic swelling (8.7 percent),
      Parkes Weber syndrome (6.5 percent), lipedema (6.5 percent), venous malformation
      (4.3 percent), rheumatologic disorder (4.3 percent), infantile hemangioma (2.2
      percent), kaposiform hemangioendothelioma (2.2 percent), or lipofibromatosis (2.2
      percent). Age of onset in children with lymphedema was older than in patients
      with another diagnosis (p = 0.027). CONCLUSIONS: "Lymphedema" is not a generic
      term. Approximately one-fourth of pediatric patients with a large lower extremity
      are misdiagnosed as having lymphedema; the most commonly confused causes are
      other types of vascular anomalies. History, physical examination, and often
      radiographic studies are required to differentiate lymphedema from other
      conditions to ensure the child is managed appropriately.

PMID- 21187805
TI  - Treatment of apert syndrome: a long-term follow-up study.
AB  - BACKGROUND: Patients with Apert syndrome have severe malformations of the skull
      and face requiring multiple complex reconstructive procedures. The authors
      present a long-term follow-up study reporting both surgical results and
      psychosocial status of patients with Apert syndrome. METHODS: A retrospective
      study was performed identifying patients with Apert syndrome treated between 1975
      and 2009. All surgical procedures were recorded and a review of psychosocial and
      educational status was obtained when patients reached adulthood. RESULTS: A total
      of 31 patients with Apert syndrome were identified; nine with long-term follow-up
      had complete records for evaluation. The average patient age was 30.4 years.
      Primary procedures performed included strip craniectomy and fronto-orbital
      advancement. Monobloc osteotomy and facial bipartition were performed in eight
      patients, and all underwent surgical orthognathic correction. Multiple auxiliary
      procedures were also performed to achieve better facial symmetry. Mean follow-up
      after frontofacial advancement was 22.5 years. Psychosocial evaluation
      demonstrated good integration of patients into mainstream life. CONCLUSIONS: This
      report presents one of the longest available follow-up studies for surgical
      correction of patients with Apert syndrome. Although multiple reconstructive
      procedures were necessary, they play an important role in enhancing the
      psychosocial condition of the patients, helping them integrate into mainstream
      life.

PMID- 21187806
TI  - Trends in level of evidence in facial plastic surgery research.
AB  - BACKGROUND: Evidence-based medicine has increasingly become an integral part of
      clinical research and practice. The purpose of this study was to assess the
      trends in the level of evidence in leading facial plastic surgery journals in
      recent years. METHODS: All scientific articles within the field of facial plastic
      surgery published in The Laryngoscope, Archives of Facial Plastic Surgery,
      Otolaryngology-Head and Neck Surgery, Journal of Plastic Surgery, and Plastic and
      Reconstructive Surgery from 1999, 2002, 2005, and 2008 were rated for level of
      evidence. The presence of p values and confidence intervals was also noted.
      RESULTS: Of 975 articles reviewed, 88 percent were clinical and 88 percent were
      therapy articles. Overall, there was an increase in the average level of evidence
      of articles published from 1999 to 2008. There was also a significant increase in
      the proportion of articles reporting p values and confidence intervals. However,
      the number of articles containing level 1 or 2 evidence remains low. CONCLUSIONS:
      With the increased demand for evidence-based medicine, facial plastic surgery
      literature has seen an overall increase in the quantity of higher level evidence
      research published. However, articles representing level 1 and 2 evidence remain
      rare.

PMID- 21187807
TI  - Systematic review of flexor tendon rehabilitation protocols in zone II of the
      hand.
AB  - BACKGROUND: Restoration of function following flexor tendon repair in zone II
      represents a difficult clinical problem. Despite many publications on
      rehabilitation methods, there exists no consensus as to which method is superior.
      This study was undertaken to determine which flexor tendon rehabilitation
      protocol provides the best outcome after surgical repair in zone II. METHODS:
      Electronic databases were searched for articles published between 1970 and 2009.
      The population included patients aged 5 years and older who sustained a flexor
      tendon laceration in zone II. The primary outcome was rupture rate. Secondary
      outcomes were range of motion and quality of life. The following protocols and
      their variations were considered: passive flexion and active extension protocols
      (Kleinert type protocols), controlled passive motion protocols (Duran type
      protocols), combination of the Kleinert and Duran protocols, and early active
      motion protocols. RESULTS: Seventy-nine articles were identified. Fifteen studies
      met the inclusion criteria. The mean rate of rupture was lowest in the combined
      Kleinert and Duran protocols (2.3 percent) and highest in the Kleinert protocols
      (7.1 percent). No statistically significant differences were found. The combined
      Kleinert and Duran protocols and the early active motion protocols exhibited the
      highest proportion of digits with excellent or good results using the Strickland
      and Buck-Gramcko systems. One study included a quality-of-life assessment
      meaningful comparison was not possible. CONCLUSIONS: Both early active motion
      protocols and combined Kleinert and Duran protocols result in low rates of tendon
      rupture and acceptable range of motion following flexor tendon repair in zone II.
      Future studies should include quality-of-life measurements using validated
      scales.

PMID- 21187809
TI  - Clinical analyses of clustered microcalcifications after autologous fat injection
      for breast augmentation.
AB  - BACKGROUND: Autologous fat injection for breast augmentation has been disputed
      with regard to its complications for many years, especially regarding
      calcifications, most of which present with benign features. In previous studies,
      clustered microcalcifications were not observed after fat injection for breast
      augmentation, which are usually regarded as malignant calcifications. METHODS:
      From July of 1999 to December of 2009, autologous fat injection for breast
      augmentation was performed for both breasts in 48 patients. Eight patients with
      clustered microcalcifications found by mammography after surgery were analyzed
      retrospectively. For the nonpalpable breast lesions in three patients, the
      clustered microcalcifications were resected with the help of needle localized
      breast biopsy. The palpable lump, including clustered microcalcifications, was
      resected 1 cm away from its border in the other patients. All of the specimens
      were submitted to pathologic examination. RESULTS: The digitized mammographic
      films of eight of 48 patients (16.7 percent) showed clustered microcalcifications
      after autologous fat injection, which were highly suspected of being breast
      carcinoma microcalcifications, whereas all pathologic examinations indicated fat
      necroses. CONCLUSIONS: Clustered microcalcifications can be found after
      autologous fat injection for breast augmentation, which cannot be distinguished
      from malignancy. The mammographic confusion constitutes the problem rather than
      the success of the procedure itself, and the method should continue to be
      prohibited.

PMID- 21187810
TI  - Plastic surgeons' satisfaction with work-life balance: results from a national
      survey.
AB  - BACKGROUND: Plastic surgery demographics are transforming, with a greater
      proportion of women and younger physicians who desire balance between their
      career and personal lives compared with previous generations. The authors'
      purpose was to describe the patterns and correlates of satisfaction with work
      life balance among U.S. plastic surgeons. METHODS: A self-administered survey was
      mailed to a random sample of American Society of Plastic Surgeons members (n =
      708; 71 percent response rate). The primary outcome was satisfaction with work
      life balance. Independent variables consisted of surgeon sociodemographic and
      professional characteristics. Logistic regression was used to evaluate correlates
      of satisfaction with work-life balance. RESULTS: Overall, over three-fourths of
      respondents were satisfied with their career; however, only half were satisfied
      with their time management between career and personal responsibilities. Factors
      independently associated with diminished satisfaction with work-life balance were
      being female (odds ratio = 0.63; 95 percent CI, 0.42 to 0.95), working more than
      60 hours per week (versus < 60 hours per week; odds ratio = 0.44; 95 percent CI,
      0.28 to 0.72), having emergency room call responsibilities (versus no emergency
      room call, odds ratio = 0.42; 95 percent CI, 0.27 to 0.67), and having a
      primarily reconstructive practice (versus primarily aesthetic practice; odds
      ratio = 0.53; 95 percent CI, 0.30 to 0.93). CONCLUSIONS: While generational
      differences were minimal, surgeons who were female, worked longer hours, and had
      emergency room call responsibilities and primarily reconstructive practices were
      significantly less satisfied with their work-life balance.

PMID- 21187811
TI  - Venous thromboembolism following microsurgical breast reconstruction: an
      objective analysis in 225 consecutive patients using low-molecular-weight heparin
      prophylaxis.
AB  - BACKGROUND: Free flap breast reconstruction involves major risk factors for
      postsurgical venous thromboembolism. The main study objectives were (1) to
      estimate objectively the incidence of symptomatic and asymptomatic lower
      extremity deep vein thrombosis in patients who received postoperative
      thromboprophylaxis after free flap breast reconstruction, (2) to evaluate the
      safety of low-molecular-weight heparin postoperatively, and (3) to assess the
      incidence of symptomatic pulmonary embolism or sudden death. METHODS: A cohort
      study of 225 consecutive patients who underwent abdominally based free flap
      breast reconstruction at a single cancer center was conducted. The postoperative
      thromboprophylaxis regimen was based on the American College of Chest Physicians
      guidelines. A study group of 118 patients systematically underwent bilateral
      lower extremity duplex ultrasound before hospital discharge to assess objectively
      the status of the lower extremity deep venous system. A retrospective cohort of
      107 women who were not systematically screened for deep vein thrombosis was used
      for comparison. RESULTS: The incidence of postoperative deep vein thrombosis
      confirmed by duplex ultrasound was 3.4 percent in the study group, all events
      being clinically silent. Bleeding complications in the entire patient sample were
      estimated at 5.3 percent. Partial flap loss and total flap loss rates were 2.7
      and 1.9 percent, respectively. No venous thromboembolism event was diagnosed in
      the control group. CONCLUSIONS: This report shows that the objective incidence of
      deep vein thrombosis was 3.4 percent within 5 postoperative days in this patient
      population. The authors' findings support the use of triple thromboprophylaxis
      and demonstrate that low-molecular-weight heparin is a safe and effective method
      for prevention of venous thromboembolism in this population.

PMID- 21187812
TI  - Antimicrobial activity of clinically used antiseptics and wound irrigating agents
      in combination with wound dressings.
AB  - BACKGROUND: A primary strategy for preventing and treating wound infection in
      chronic wounds is the use of topical antiseptics and wound irrigating agents.
      However, their interaction with commonly used wound dressings has not yet been
      investigated. In this study, the authors analyzed the antimicrobial activity of
      antiseptics and wound irrigating agents used with commercially available wound
      dressings. METHODS: Five clinically used antiseptics and wound irrigating agents
      (Prontosan, Lavasept, Braunol, Octenisept, and Betaisodona) were tested in the
      presence or absence of 42 wound dressings against Staphylococcus aureus. The
      determination of antibacterial activity was performed by disk diffusion assay.
      RESULTS: Povidone-iodine-based products showed sufficient antimicrobial activity
      in 64 to 78 percent of the combinations assessed (p > 0.01). The octenidine
      derivate Octenisept showed sufficient antimicrobial activity in 54 percent of
      combinations. Polyhexamethylene biguanide derivatives demonstrated sufficient
      antimicrobial activity in 32 percent of the combinations. CONCLUSION: This study
      revealed that commonly used wound dressings dramatically reduce antibacterial
      activity of clinically used antiseptics and wound irrigating agents in vitro.

PMID- 21187813
TI  - Triterpenoid contents and anti-inflammatory properties of the methanol extracts
      of ligustrum species leaves.
AB  - Ligustrum (privet) plants are used by Chinese physicians to prevent and cure
      hepatitis and chronic bronchitis. Three common Ligustrum plant spp., namely
      Ligustrum lucidum Ait. (LL), L. pricei Hayata (LP) and L. sinensis Lour. (LS)
      were collected to assess their analgesic/anti-inflammatory properties on chemical
      induced nociception and carrageenan-induced inflammation in rodents. The methanol
      extracts from Ligustrum plants leaves effectively inhibited nociceptive responses
      induced by 1% acetic acid and 1% formalin. LP and LL reduced the edema induced by
      1% carrageenan. LP exhibited the best potency of the Ligustrum plants.
      Furthermore, LP reduced the abdominal Evan's blue extravasations caused by
      lipopolysaccharide, lipoteichoic acid, autocrines and sodium nitroprusside. The
      triterpenoid content of the three Ligustrum spp. was measured by high performance
      liquid chromatography using a photodiode array detector. LP contained the highest
      content of amyrin, betulinic acid and lupeol. LL had the highest content of
      oleanolic acid and ursolic acid. The various degrees of analgesic/anti
      inflammatory effects among three Ligustrum plants may be related to their
      different triterpenoid contents. LP is a potential analgesic and anti
      inflammatory Ligustrum plant. The effects of LP are partially related to the
      inhibition of cyclooxygenase-2 activity and a decrease in microvascular
      permeability via the actions of autocrines and kinins.

PMID- 21187814
TI  - Novel synthesis of hydrazide-hydrazone derivatives and their utilization in the
      synthesis of coumarin, pyridine, thiazole and thiophene derivatives with
      antitumor activity.
AB  - The reaction of cyanoacetyl hydrazine (1) with 3-acetylpyridine (2) gave the
      hydrazide-hydrazone derivative 3. The latter compound undergoes a series of
      heterocyclization reactions to give new heterocyclic compounds. The antitumor
      evaluation of the newly synthesized products against three cancer cell lines,
      namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and
      CNS cancer (SF-268) was performed. Most of the synthesized compounds showed high
      inhibitory effects.

PMID- 21187815
TI  - Anti-fatigue activity of extracts of stem bark from Acanthopanax senticosus.
AB  - In the present study, we investigated the anti-fatigue activity in male Kunming
      mice of extracts of stem bark from Acanthopanax senticosus (ASSE) using a forced
      swimming test. Mice were divided into four groups (three ASSE administered groups
      and the control group). The control group were gavaged with distilled water and
      ASSE administered groups were gavaged with ASSE (100, 200 and 400 mg/kg). After
      four weeks, a forced swimming test was performed and the biochemical parameters
      related to fatigue were examined. The results suggested that ASSE could extend
      the swimming time to exhaustion of the mice, as well as increase the tissue
      glycogen contents, while decreasing the blood lactate and serum urea nitrogen
      contents. This indicated that ASSE had anti-fatigue activity and could elevate
      the exercise tolerance.

PMID- 21187816
TI  - Enhancement in the catalytic activity of Pd/USY in the heck reaction induced by
      H2 bubbling.
AB  - Pd was loaded on ultra stable Y (USY) zeolites prepared by steaming NH(4)-Y
      zeolite under different conditions. Heck reactions were carried out over the
      prepared Pd/USY. We found that H2 bubbling was effective in improving not only
      the catalytic activity of Pd/USY, but also that of other supported Pd catalysts
      and Pd(OAc)2. Moreover, the catalytic activity of Pd/USY could be optimized by
      choosing appropriate steaming conditions for the preparation of the USY zeolites;
      Pd loaded on USY prepared at 873 K with 100% H2O gave the highest activity (TOF =
      61,000 h-1), which was higher than that of Pd loaded on other kinds of supports.
      The prepared Pd/USY catalysts were applicable to the Heck reactions using various
      kinds of substrates including bromo- and chloro-substituted aromatic and
      heteroaromatic compounds. Characterization of the acid properties of the USY
      zeolites revealed that the strong acid site (OH(strong)) generated as a result of
      steaming had a profound effect on the catalytic activity of Pd.

PMID- 21187817
TI  - Novel synthesis and antitumor evaluation of polyfunctionally substituted
      heterocyclic compounds derived from 2-cyano-N-(3-cyano-4,5,6,7
      tetrahydrobenzo[b]thiophen-2-yl)-acetamide.
AB  - The reaction of 2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene with ethyl
      cyanoacetate gave 2-cyano-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)
      acetamide. The latter was used to synthesize different heterocyclic derivatives
      comprising thiophene, thiazole, pyrazole, pyridine, pyrimidine, and coumarin
      rings. The mechanistic and synthetic pathways depended on regioselective attack
      and/or cyclization by the cyanoacetamido moiety in the key precursor on various
      chemical reagents. The competition of the reaction pathways including dipolar
      cyclization, dinucleophilic-bielectrophilic attack, beta-attack, Gewald-type
      attack, and condensation reactions led to the diversity of the synthesized
      products. The antitumor activities of the synthesized products were studied and
      evaluated. Most of the compounds revealed high inhibitory effects when screened
      in vitro for their antiproliferative activity. Three human cancer cell lines,
      namely, breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and
      CNS cancer (SF-268) were used in the screening tests. The simplicity of the
      synthetic procedures which mainly involved one-pot reactions under mild reaction
      conditions, the convenience of yield production and the diversity of the reactive
      sites in the produced systems play a valuable role for further heterocyclic
      transformations and further biological investigations.

PMID- 21187818
TI  - Vitamin levels in a selected population in the Czech Republic.
AB  - OBJECTIVES: The work objective was to monitor nutritional habits in the observed
      group of professional soldiers with the focus on eating food with the content of
      antioxidant carriers. Then to show present state of health and nutrition in the
      group on the basis of anthropometric measurements and biochemical examinations
      and finally to observe the level of antioxidant vitamins in the observed group of
      professional soldiers. METHODS: The group included 171 healthy individuals, 152
      men and 19 women. Their average age was 34.2+/-7.9 years. The venous blood was
      taken for biochemical examinations in all individuals on a fast. Anthropometric
      measurements (weight, height, caliperation, waist circumferences), blood pressure
      and pulse were taken continually in all individuals. Simple questionnaires were
      administered to all participants for the complete evaluation of present health
      and for the registration of eating habits of the observed persons. RESULTS: The
      study results show that retinol and a-tocoferol levels in the observed group were
      within a normal range. The average concentration of vitamin C in this group was
      54 mmol/l and reached nearly the values given in other European countries. But
      concentrations of beta-caroten and lycopen in serum were up to 50% lower in
      comparison with concentrations in population in the countries of West Europe.
      Higher vitamin C and beta caroten serum levels were found in individuals who
      respond in a questionnaire they eat fruit and vegetables or supplements of
      vitamin preparations every day. Statistically lower levels of vitamin C, beta
      karoten and lycopen in the group of obese people (compared with the group of
      normal weight people) show decreased level of antioxidant protection of the
      organism and the risk of cardiovascular diseases. CONCLUSIONS: The results show
      that it is necessary to ensure optimal food not only with an energetic diet value
      but also with a proper input of antioxidant carriers in the form of fresh
      vegetables and fruit every day.

PMID- 21187819
TI  - Suppression of oxidative burst in human neutrophils with the naturally occurring
      serotonin derivative isomer from Leuzea carthamoides.
AB  - OBJECTIVE: Neutrophil leukocytes and macrophages represent professional
      phagocytic cells. When appropriately stimulated, they undergo dramatic
      physiological and biochemical changes resulting in phagocytosis, chemotaxis and
      degranulation with the activation of reactive oxygen species (ROS) production
      known as the respiratory burst. DESIGN: In this study we analysed the effect of a
      crystalline complex fraction of four N-feruloyl-serotonin isomers isolated from
      the seeds of Leuzea carthamoides on the mechanism of oxidative burst of human
      neutrophils in vitro. RESULTS: N-feruloyl-serotonin (N-f-5HT) inhibited dose
      dependently oxidative burst of human whole blood and isolated neutrophils in
      vitro stimulated with phorbol-myristate-acetate (PMA) as measured by
      luminol/isoluminol enhanced chemiluminescence.In isolated neutrophils stimulated
      with PMA, N-f-5HT was effective against extracellular as well as intracellular
      reactive oxygen species. Western blot analysis documented that N-f-5HT in
      concentrations of 10 and 100 uM significantly decreased PMA-induced
      phosphorylation of protein kinase C alpha/beta II. CONCLUSION: The results
      suggest that N-f-5HT represents an effective naturally occurring substance with
      potent effect on the oxidative burst of human neutrophils and could be further
      investigated for its pharmacological activity against oxidative stress in
      ischaemia-reperfusion, inflammation and other pathological conditions.

PMID- 21187820
TI  - Study on apoptotic effects of neurotoxin anatoxin-a on fish immune cells.
AB  - OBJECTIVES: The aim of this study was to assess the possible in vitro apoptotic
      effects of anatoxin-a on the selected immune cells isolated from the blood of
      carp. DESIGN: In the experiments pure anatoxin-a was used at concentrations of
      0.01, 0.05, 0.1 and 1 ug/ml RPMI-1640 medium. Apoptosis or necrosis of fish
      leukocytes (lymphocytes and phagocytes) induced by the toxin was determined by
      measurement of the activity of caspases-3/7 and the analysis of
      phosphatidylserine on the outer leaflet of apoptotic cell-membranes using Annexin
      V-Fluorescein and Propidium Iodide. Moreover, fluorescent measurement of the
      release of lactate dehydrogenase from the cells with damaged membranes was done.
      RESULTS: The viability of the lymphocytes exposed only to the highest
      concentration of anatoxin-a (1 ug/ml) was significantly decreased. The exposure
      to the toxin at higher concentrations (0.1 and 1 ug/ml) resulted in a significant
      increase of caspases 3/7 activity in phagocytes and lymphocytes. Moreover,
      fluorescent analysis with the use of annexin-V-fluorescein and propidium iodide
      staining showed more cells at the apoptotic stage than necrotic cells.
      CONCLUSION: Our study showed that anatoxin-a is an inducer of apoptosis in fish
      immune cells.

PMID- 21187821
TI  - Role of cytochromes P450 and peroxidases in metabolism of the anticancer drug
      ellipticine: additional evidence of their contribution to ellipticine activation
      in rat liver, lung and kidney.
AB  - OBJECTIVE: Ellipticine is a potent antineoplastic agent exhibiting multiple
      mechanisms of action. This anticancer agent should be considered a pro-drug,
      whose pharmacological efficiency and/or genotoxic side effects are dependent on
      its cytochrome P450 (CYP)- and/or peroxidase-mediated activation to species
      forming covalent DNA adducts. The target of this study was to investigate a role
      of CYP and peroxidase enzymes in ellipticine oxidative activation in rats, a
      suitable model mimicking the fate of ellipticine in humans, in details. The
      contribution of pulmonary and renal CYP- and peroxidase enzymes to ellipticine
      metabolic activation is investigated and compared with that found in the liver.
      METHODS: Ellipticine oxidation and DNA adduct formation in vitro were
      investigated using microsomes isolated from liver, lung and kidney of rats,
      either control (untreated) or treated i.p. with a single dose of 40 mg of
      ellipticine per kg of body weight. HPLC with UV detection was employed for the
      separation and characterization of ellipticine metabolites. Inhibitors of CYPs
      and cyclooxygenase (prostaglandin H synthase, COX) were used to characterize the
      enzymes participating in ellipticine oxidative activation in rat liver, lung and
      kidney. Ellipticine-derived DNA adducts were detected by 32P-postlabeling.
      RESULTS: Using alpha-naphthoflavone, furafylline and ketoconazole, inhibitors of
      CYP1A, 1A2 and 3A, respectively, we found that the CYP1A and 3A enzymes play a
      major role in ellipticine activation to species forming DNA adducts in liver
      microsomes. Because of lower expression of these enzymes in lungs and kidneys,
      even after their induction by ellipticine, they play a minor role in ellipticine
      activation in these extrahepatic tissues. Arachidonic acid, a cofactor of COX,
      increased ellipticine activation in the microsomes of extrahepatic tissues. In
      addition, indomethacin, an inhibitor of COX, efficiently inhibited formation of
      ellipticine-derived DNA adduct in these microsomes. Based on these results, we
      attribute the higher activation of ellipticine in lung and kidney microsomes to
      COX than to CYP enzymes. CONCLUSION: The results demonstrate that whereas CYP
      enzymes of 1A and 3A subfamilies are the major enzymes activating ellipticine in
      rat livers, peroxidase COX plays a significant role in this process in lungs and
      kidneys.

PMID- 21187822
TI  - Pharmacokinetics and organ distribution of fluorescein in experimental pigs: an
      input study for confocal laser endomicroscopy of the gastrointestinal tract.
AB  - OBJECTIVE: Confocal laser scanning endomicroscopy (CLSE) is a diagnostic
      technology that produces virtual histology of the mucosal layer using
      fluorescence technique. Fluorescein (FSC) is the most commonly used fluorescence
      agent. Fluorescence light coming from a horizontal special focal plane is
      detected during confocal laser endomicroscopy of the gastrointestinal tract. FSC
      causes intensive yellowish discoloration of tissues, including skin and mucous
      membranes. This pre-clinical study was aimed to evaluate the tissue distribution
      and pharmacokinetics of FSC after its intravenous administration. METHODS: The
      study was performed in an adult experimental pig. A reversed-phase high
      performance liquid chromatographic method with fluorescence detection was used
      for the determination of fluorescein in blood plasma and tissue samples. RESULTS
      AND CONCLUSION: The pharmacokinetic study of fluorescein determined the optimum
      time interval for diagnostic scanning (5-10 min.) The biodistribution study of
      fluorescein (aimed on the potential organ accumulation) proved the high
      concentration in the renal system followed by levels in bile > lung > adipose
      tissue > all other organs (including gastrointestinal wall) and these were
      relatively similar to each other. Fluorescein has a significantly low
      distribution in the brain (contrast with the level in adipose tissue indicates
      the low ability to penetrate the blood-brain barrier).

PMID- 21187823
TI  - Newborn with neonatal form of molybdenum cofactor deficiency - the first patient
      in the Slovak Republic.
AB  - OBJECTIVE: To present the case of a term newborn with rapid progression of signs
      of neurodegenerative disease. RESULTS: In a case of a term newborn with numerous
      dysmorphic features, with seizure activity from the 3rd day of life, hypertonia
      and serious changes on brain parenchyma were presented. Diagnosis of molybdenum
      cofactor deficiency was confirmed by the decreased level of uric acid, 31
      MUmol/l, in serum, increased excretion of thiosulfate and S-sulfocysteine in
      urine, taurine (1729.3 MUmol/mmol crea; normal range 30-300 MUmol/mmol crea) and
      xanthine (276.9 MUmol/mmol crea; normal range < 25 MUmol/mmol crea) in urine.
      Sulfite oxidase activity on skin fibroblasts in culture was not detectable. The
      patient died at the age of 28 days of life. CONCLUSION: Deficiency of molybdenum
      cofactor leads to accumulation of toxic metabolites (levels of sulfite), which
      causes disturbances of neurotransmitters even before delivery. Therapy is
      symptomatic, no effective therapy is available. Seizures are difficult to
      suppress. This case report is about the first patient in Slovakia.

PMID- 21187824
TI  - Molecular targets of the natural antioxidant pterostilbene: effect on protein
      kinase C, caspase-3 and apoptosis in human neutrophils in vitro.
AB  - OBJECTIVE: Pterostilbene, a naturally occurring phenolic derivative, exhibits
      various pharmacological effects, e.g. anti-cancerous, antioxidant, anti
      inflammatory and anti-diabetic. Based on our previous study, we assessed the
      cellular and molecular effects of pterostilbene on human neutrophils and in cell
      free systems. Experimental and theoretical molecular descriptors of stilbene
      derivatives were also determined. METHODS: We assessed the antioxidant properties
      of pterostilbene using cell free system and computational methods. The effect of
      pterostilbene on protein kinase C activation/phosphorylation was detected by
      special anti-phospho protein kinase C antibodies. Membrane associated changes
      determining the life span of neutrophils and human recombinant caspase-3 assay
      were examined. RESULTS: Pterostilbene possessed comparable antioxidant properties
      as resveratrol in cell free system. Computational methods were used to establish
      the molecular characteristics of stilbene derivatives. The values of electronic
      parameters suggest a slight enhancement of electron donor properties of
      pterostilbene compared to resveratrol. Phosphorylation and thus activation of
      protein kinase C alpha/beta II in activated neutrophils was not decreased by
      pterostilbene. Pterostilbene in concentrations of 10-100 MUM was found to inhibit
      the activity of human caspase-3 purified enzyme and did not influence cell
      viability significantly. CONCLUSION: Pterostilbene, an analog of resveratrol, was
      identified as a good natural antioxidant compound. However, reducing the
      oxidative burst of human neutrophils during their activation in vitro with
      pterostilbene does not include protein kinase C phosphorylation pathway.
      Pterostilbene showed dose dependent activation/inhibition of caspase-3 enzyme
      activity.

PMID- 21187825
TI  - Modulation of ionising radiation generated oxidative stress by HI-6 (asoxime) in
      a laboratory rat model.
AB  - OBJECTIVES: HI-6 is an antidotum suitable for treatment of intoxication by nerve
      agents. The recent investigation appointed its modulation of inflammatory
      response as well as vegetative nervous system activity. However, the present
      experiments were carried out in order to assess the antioxidant effect of HI-6 in
      irradiated animals. METHODS: male Wistar rats were irradiated by ionizing
      radiation (7.5 Gy, LD50/30). Animals were divided into four groups: i.e. controls
      (A), irradiated (B), treated with HI-6 (C), and both irradiated and treated with
      HI-6 (D). Ferric reducing antioxidant power (FRAP), thiobarbituric acid reactive
      substances (TBARS) and glutathione reductase activity were assayed in liver,
      spleen, plasma, and whole blood. Clinical biochemistry markers were determined in
      plasma samples. RESULTS: We found significantly increased FRAP levels in liver,
      while its levels decreased in the spleen of B group animals. Ionising radiation
      (B group) also significantly elevated TBARS values in spleen. HI-6 reversed FRAP
      and TBARS values to control levels. Glutathione reductase activity was
      significantly elevated in spleen and liver of animals exposed to HI-6 (C and D
      groups). Clinical biochemistry markers were shifted only slightly. The in vitro
      test confirmed the inhibitory effect of HI-6 towards acetylcholinesterase.
      CONCLUSIONS: In conclusion, HI-6 is potent in suppressing oxidative stress and
      might be a promising drug in the field of radiation protection.

PMID- 21187826
TI  - In vivo effect of pinosylvin and pterostilbene in the animal model of adjuvant
      arthritis.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of pinosylvin (PIN)
      and pterostilbene (PTE), natural substances from the stilbenoid group, on the
      development of adjuvant arthritis in rats. METHODS: Adjuvant arthritis (AA) was
      induced by a single intradermal injection of Mycobacterium butyricum in
      incomplete Freund's adjuvant in male Lewis rats. Our experiments included healthy
      intact animals as reference controls, arthritic animals without any drug
      administration, and arthritic animals with administration of PIN and PTE in the
      oral daily dose of 30 mg/kg b.w. The treatment involved administration of the
      substances tested from day 0, i.e. the day of immunization, to the experimental
      day 28. The following parameters were monitored: change of the hind paw volume
      (HPV) on day 14, 21 and 28, luminol-enhanced chemiluminescence (CL) of the joint
      and myeloperoxidase (MPO) activity in hind paw joint homogenates (day 28).
      RESULTS: Arthritic animals treated with PIN showed a decrease in HPV,
      significantly on days 14 and 28. PIN decreased CL of the joint as well as MPO
      activity of the joint homogenate, in comparison with untreated animals. PTE had
      no effect on HPV and MPO activity in hind paw joint homogenates and exerted only
      a partial effect on luminol-enhanced CL. CONCLUSIONS: On the basis of our results
      we conclude that the effect of PTE on CL was only partial. PIN, on the other
      hand, had a beneficial anti-inflammatory and antioxidant effect on oxidative
      stress induced biochemical changes occurring in AA, as determined by all three
      functional parameters.

PMID- 21187827
TI  - Identification of rat cytochromes P450 metabolizing N-(2
      methoxyphenyl)hydroxylamine, a human metabolite of the environmental pollutants
      and carcinogens o-anisidine and o-nitroanisole.
AB  - OBJECTIVES: N-(2-methoxyphenyl)hydroxylamine is a human metabolite of two
      industrial and environmental pollutants and bladder carcinogens 2-methoxyaniline
      (o-anisidine) and 2-methoxynitrobenzene (o-nitroanisole). Metabolism of N-(2
      methoxyphenyl)hydroxylamine by rat hepatic microsomes and identification of the
      major microsomal enzymes participating in this process are aims of this study.
      METHODS: HPLC with UV detection was employed for the separation of N-(2
      methoxyphenyl)hydroxylamine metabolites. Inducers and inhibitors of microsomal
      enzymes and rat recombinant CYPs were used to characterize the enzymes
      participating in N-(2-methoxyphenyl)hydroxylamine metabolism. RESULTS: N-(2
      methoxyphenyl)hydroxylamine is metabolized by rat hepatic microsomes
      predominantly to o-anisidine, the parent carcinogen from which N-(2
      methoxyphenyl)hydroxylamine is formed, while o-aminophenol and two N-(2
      methoxyphenyl)hydroxylamine metabolites, whose exact structures have not been
      identified as yet, are minor products. Selective inhibitors of microsomal CYPs,
      NADPH:CYP reductase and NADH:cytochrome b5 reductase and hepatic microsomes of
      rats pre-treated with specific inducers of CYPs and NADPH:CYP reductase were used
      to characterize rat liver microsomal enzymes reducing N-(2
      methoxyphenyl)hydroxylamine to o-anisidine. Based on these studies, we attribute
      most of N-(2-methoxyphenyl)hydroxylamine metabolism to o-anisidine in rat liver
      to CYP2C, followed by CYP2E1, 2D and 2A. Among recombinant rat CYP enzymes tested
      in this study, rat CYP2C11 and 2E1, followed by CYP2A2, 2D1/2, 2C12, 3A1/2 and
      1A1/2 were the most efficient enzymes metabolizing N-(2
      methoxyphenyl)hydroxylamine to o-anisidine. CONCLUSION: The results found in this
      study, the first report on the reduction of N-(2-methoxyphenyl)hydroxylamine by
      rat CYP enzymes, demonstrate that CYP2C, followed by CYP2E1, 2D and 2A are the
      major enzymes participating in this process in rat liver.

PMID- 21187828
TI  - Formation of reactive oxygen and nitrogen species in the presence of pinosylvin -
      an analogue of resveratrol.
AB  - OBJECTIVE: Formation of reactive oxygen species in neutrophils of rats with
      adjuvant arthritis and generation of nitric oxide in RAW 264.7 macrophages were
      analysed in the presence of pinosylvin. METHODS AND RESULTS: The method of
      chemiluminescence was used for the detection of reactive oxygen species in blood
      of rats with adjuvant arthritis. Pinosylvin (50 mg/kg, daily, p.o.) and
      methotrexate (0.4 mg/kg, twice a week, p.o.) were applied separately or in a
      combination over a period of 28 days from the day of immunisation. Adjuvant
      arthritis was accompanied by a significantly increased number of neutrophils, by
      elevated concentration of oxidants in blood and by excessive responsiveness of
      neutrophils to stimulation with PMA. In rats treated with methotrexate, all these
      changes were significantly reduced and the inhibition became more pronounced when
      methotrexate was applied in the combination with pinosylvin; the monotherapy with
      pinosylvin did not induce any detectable changes in the parameters tested. Under
      in vitro conditions, pinosylvin inhibited formation of nitric oxide (NO) in
      macrophages, as demonstrated by the decreased concentration of nitrite - the end
      product of NO metabolism (assessed by Griess' method), by the reduced expression
      of inducible NO synthase (detected by Western blot), and by the failure of
      pinosylvin to scavenge nitric oxide (measured amperometrically in cell-free
      system). CONCLUSION: The observed ability of pinosylvin to decrease concentration
      of reactive oxygen and nitrogen species, along with its capacity to enhance the
      efficacy of methotrexate in arthritis treatment may shed more light into the
      pharmacological potential of this prospective natural substance.

PMID- 21187829
TI  - Evaluation of genotoxic potential of neurotoxin anatoxin-a with the use of umuC
      test.
AB  - OBJECTIVE: The aim of this study was to evaluate genotoxicity of anatoxin-a,
      cyanotoxin of neurotoxic activity. Additionally, other frequently detected
      cyanotoxin of previously described genotoxic potential, microcystin-LR, was used
      at the same concentrations, as well as the mixture of both toxins, anatoxin-a and
      microcystin-LR. DESIGN: Genotoxicity of the toxins was determined with the use of
      the umuC assay, in which the induction and expression of the umuC - lacZ reporter
      gene was assessed. The test was conducted on Salmonella typhimurium TA
      1535/pSK1002 strain, with and without metabolic transformation. The toxin
      concentrations were 0.25, 0.5, 1 and 2 ug/ml. The exposure time was 2 h. RESULTS:
      The highest inefficient concentration of anatoxin-a without metabolic
      transformation was 0.25 ug/ml, of microcystin-LR was 0.5 ug/ml and in case of the
      toxin mixture all used concentrations induced the umuC gene. When S9 fraction was
      added to the samples, no effects were detected. CONCLUSION: To our knowledge,
      this is the first report on genotoxic effects of anatoxin-a. Although the study
      is preliminary and needs further research, however, indicates the new potential
      activity of the toxin, as well as the possible increase of genotoxicity of other
      cyanotoxins, more stable in the environment, e.g. microcystin-LR.

PMID- 21187830
TI  - Embryotoxicity of mirtazapine: a study using Chick Embryotoxicity Screening Test.
AB  - OBJECTIVE: Mirtazapine is a new antidepressant used in last years, however
      experience with it during pregnancy is unsatisfactory on the present. Its wide
      therapeutic range and only little proved side effects may be an advantage for
      treatment during pregnancy. Aim of our study was to contribute to the knowledge
      on possible risks. MATERIALS AND METHODS: For embryotoxicity testing we used an
      alternative method - CHEST, that used chicken embryos as experimental model.
      Fertilized eggs of outbred Grey Leghorn stock (AVCR farm Kolec) were treated on
      embryonic day (ED) 4 by Mirtazapine, incubated till 9ED, when they were weighed
      and examined. Summing the proportions of dead and malformed embryos, the
      beginning of the embryotoxicity dose range was estimated. RESULTS: Mirtazapine
      solved in 15% DMSO in water revealed low embryotoxicity corresponding data from
      preclinical studies. If 100% DMSO was used as a solvent, the dose 0.05 MUg/3 MUL
      resulted in 57% mortality (LD50). Typical malformations were microphtalmia and
      malformation (shortening) of limbs on left side, which is a place of contact the
      embryonic body with maximal Mirtazapine concentration. Approximation of doses in
      chick embryos to mammals is complicated by low solubility of mirtazapine.
      CONCLUSIONS: If the embryotoxic dose was close to LD50, risk at therapeutical
      doses will be probably low. Mirtazapine according to results of testing and cases
      published in literature is relatively safe for pregnant women, only higher rate
      of abortions was demonstrated, however more information is needed to exclude all
      potential risks.

PMID- 21187831
TI  - Effects of subchronic exposure to Spartakus (prochloraz) on common carp Cyprinus
      carpio.
AB  - OBJECTIVES: The aim of the study was to investigate effects of the fungicide
      formulation Spartakus (prochloraz 450 g.L-1) on common carp Cyprinus carpio
      through biometric, biochemical, haematological and antioxidant indices, induction
      of xenobiotic metabolizing enzymes and histological examination of selected
      tissues. DESIGN: The test was performed on juvenile fish, which was exposed to
      Spartakus (concentrations of prochloraz: 0.05; 0.15 and 0.38 mg.L-1) for 28 days.
      Haematological indices were assessed using unified methods of haematological
      examination in fish. Plasma biochemical indices were determined by biochemical
      analyzer. Concentration of total cytochrome P450 (CYP), glutathione (GSH) content
      and glutathione-S-transferase (GST) activity were determined
      spectrophotometrically in hepatopancreas. Activity of liver ethoxyresorufin-O
      deethylase (EROD) activity was measured spectrofluorimetrically. Ferric reducing
      ability of plasma (FRAP) and ceruloplasmin activity were assessed
      spectrophotometrically. Histological changes in samples of hepatopancreas, skin,
      gills, spleen, head kidney and caudal kidney were examined by light microscopy.
      RESULTS: There was a significant rise in hepatosomatic index (HSI) (p<0.01), CYP
      and EROD (p<0.05) of fish exposed to prochloraz of 0.15 and 0.38 mg.L-1 whereas
      GST was induced by all concentrations tested and GSH by 0.38 mg.L-1 (p<0.05). Red
      blood cell count decreased significantly (p<0.05) in prochloraz of 0.05 and 0.15
      mg.L-1. Plasma potassium increased (p<0.01) in all Spartakus treated groups, a
      decline in total protein (p<0.05), ALT, Na+ and Ca (p<0.01) was found in fish
      exposed to prochloraz of 0.38 mg.L-1. Ceruloplasmin activity was elevated
      (p<0.05) in the highest concentration tested, FRAP declined (p<0.05) in the same
      group. Histopathological changes in gills were demonstrated in all pesticide
      treated groups, with a decreased activity of skin mucous cells in prochloraz of
      0.38 mg.L-1. CONCLUSION: The subchronic exposure to Spartakus influenced HSI,
      induced xenobitic metabolizing enzymes, initiated a disorder of selected plasma
      indices and a decline in red blood cell count, caused minor histological
      impairment, and affected antioxidant activities of the test fish.

PMID- 21187832
TI  - Effects of probiotic Escherichia coli Nissle 1917 on expression of cytochromes
      P450 along the gastrointestinal tract of male rats.
AB  - OBJECTIVES: The aim of the study was to find whether probiotic Escherichia coli
      Nissle 1917 O6:K5:H1 (EcN) influences the expression of cytochromes P450 (CYP) in
      the rat intestine. DESIGN: Live bacterial suspension of EcN was administered to
      healthy male Wistar rats daily for 7 days. Control group of rats was stressed by
      oral application of the saline solution daily for 7 days as well. Sections of the
      duodenum, jejunum, ileum, caecum and colon have been taken from each experimental
      animal. With all individual samples, microsomal fraction has been prepared and
      expression of selected CYPs was determined by Western blotting. The levels of
      expression of CYPs were also evaluated by mRNA using real-time PCR. RESULTS: It
      was found that there are changes in expression of CYP enzymes studied along the
      intestine. CYP1A1, 2B1/2 and 2E1 are present mainly in the duodenum and jejunum;
      on the other hand, CYP2C6 is expressed mainly in the caecum and colon. CYP3A was
      found all over the rat intestine. The results show that there are no prominent
      differences between control samples and samples with EcN, only the expression of
      CYP3A protein in the duodenum appears to exhibit a clear tendency to decrease. In
      the case of the colon, a significant increase in the expression of CYP3A (most
      likely CYP3A1) after treatment of rats with EcN was found. CONCLUSION: This in
      vivo study revealed that the levels of colon CYP3A could be significantly
      increased in rats treated with probiotic EcN. On the contrary, the expression of
      CYP3A in the duodenum decreased. However, the changes in the expression of CYP
      enzymes are probably not as extensive to be clinically important in man; hence,
      most likely the probiotic EcN has little influence on the intestinal drug
      metabolism by CYP enzymes.

PMID- 21187833
TI  - Effects of high dietary levels of Se-enriched yeast on tissues selenium content
      and meat quality traits - a model study in rats.
AB  - OBJECTIVES: The aim of the trial was to evaluate effects of high dietary levels
      of Se-enriched yeast on selenium concentrations in muscle and liver tissue and on
      the meat quality traits in rats. DESIGN: The experimental feed mixtures were fed
      to Wistar Albino rats for a period of 10 weeks. They differed in the dose and in
      the form of Se supplement. Supplemental dose of 0.3 mg.kg-1 of Se per one
      kilogram of feed was used in group I (n = 10, sodium selenite) and in group II (n
      = 10, Se-enriched yeast). Elevated dose 2 mg.kg-1 Se per one kilogram of feed was
      used in group III (n = 10, sodium selenite) and in group IV (n = 10, Se-enriched
      yeast). RESULTS: The use of elevated dietary Se level (2 mg.kg-1) in the form of
      sodium selenite did not increase lipid oxidation (malondialdehyde content) in
      muscles nor influenced meat quality traits. The use of elevated dietary Se level
      in the form of Se-enriched yeast resulted in higher Se muscle concentrations
      accompanied by increased of malondialdehyde content. The meat quality traits
      remained unaffected. CONCLUSION: High selenium concentrations in muscle produced
      by Se-enriched yeast were accompanied by elevated MDA levels, but it did not
      negatively influence meat quality traits.

PMID- 21187834
TI  - Toxcon 2010, borderless toxicology.

PMID- 21187835
TI  - Different effect of two synthetic coumarin-stilbene hybrid compounds on phagocyte
      activity.
AB  - OBJECTIVE: Activated phagocytes, generating a variety of powerful inflammatory
      mediators, such as oxygen and nitrogen species, may participate in oxidative
      stress-mediated inflammation and organ toxicity. At present, great attention is
      devoted to the important class of phenolic compounds - coumarins - due to their
      antiinflammatory/antioxidant activities. We compared two synthetic
      phenylcoumarins: 7-hydroxy-3-(4'-hydroxyphenyl) coumarin (HHC; 0.01-100 umol/l)
      and its hydrogenated analogue: 7-hydroxy-3-(4'-hydroxyphenyl)-3,4-dihydrocoumarin
      (HHDC; 0.01-100 umol/l) as their ability to inhibit reactive oxygen species (ROS)
      generation in human neutrophils and nitric oxide (NO) production by RAW 264.7
      macrophages in vitro, with respect to some of their physicochemical
      characteristics. METHODS: ROS production was measured with luminol-enhanced
      chemiluminescence (CL) in the microplate luminometer Immunotech LM-01T, nitrite
      formation was determined by the Griess reaction - spectrophotometrically. The
      radical scavenging assays were employed to assess the antiradical activity
      values. The relevant physico-chemical parameters of the compounds tested,
      electronic and hydrophobic, were determined experimentally as well as by suitable
      computational programmes. RESULTS: Both HHC and HHDC were found to decrease
      significantly (p<0.01) CL of whole blood stimulated with phorbol myristate
      acetate (PMA) from the concentration of 1 umol/l. While HHC significantly
      inhibited CL stimulated by A23187 and opsonized zymosan (OpZ), HHDC was
      ineffective. Unlike HHDC, HHC in the concentrations of 10 and 100 umol/l
      significantly (p<0.01) reduced NO formation in lipopolysaccharide (LPS) 
      stimulated murine macrophages RAW 264.7. HHC possessed the higher free radical
      reducing efficacy in accordance with its more favourable values of electronic
      parameters in comparison with HHDC. CONCLUSIONS: Our results show the different
      inhibitory effects of HHC and HHDC on phagocytic activity that might be the
      result of their diverse free radical scavenging properties and lipophilicity
      features.

PMID- 21187836
TI  - Cytotoxic and genotoxic effect of methanolic flower extract from Gentiana
      asclepiadea on COS 1 cells.
AB  - OBJECTIVE: The purpose of this study was to assess whether a methanol extract
      isolated from the flower of Gentiana asclepiadea had potential cytotoxic or
      genotoxic effect on COS 1 (monkey kidney) cell line. Five various concentrations
      of the extract were investigated for cytotoxicity and genotoxicity and to
      determine non-cytotoxic and non-genotoxic concentrations suitable for utilization
      in pharmacology and medicine. METHODS: Cytotoxicity was determined using the
      proliferation (growth activity) and the plating efficiency (colony forming
      ability) assays after 24 hour incubation of COS 1 cells with different
      concentrations of methanolic flower extract from G. asclepiadea. To assess
      potential genotoxicity, the comet assay or SCGE (Single-Cell Gel Electrophoresis)
      was used. RESULTS: We found that only the highest (5 and 25 mg/ml) concentrations
      of the extract revealed cytotoxic and genotoxic effect. We have also determined
      concentrations that stimulated cell growth (0.25 mg/ml) and colony forming
      ability (0.25-2.5 mg/ml) and did not exhibit genotoxic effect (0.25-2.5 mg/ml).
      CONCLUSIONS: We found out that extract of G. asclepiadea was neither cytotoxic
      nor genotoxic in a wide range of concentrations (0.25-2.5 mg/ml) and thus can be
      used to further investigate potential beneficial usage in pharmacology and
      medicine.

PMID- 21187837
TI  - Carnosine inhibits degradation of hyaluronan induced by free radical processes in
      vitro and improves the redox imbalance in adjuvant arthritis in vivo.
AB  - OBJECTIVE: New ways of supplementary or combinatory therapy of rheumatoid
      arthritis (RA) are of great importance. The aim is to find an additive to
      classical RA therapy with natural molecules without side effects possessing anti
      inflammatory and anti-oxidative properties. In this study we investigated the
      anti-oxidative and anti-inflammatory properties of the endogenous natural
      compound carnosine (CARN) in vitro and in vivo. Moreover, we tested also the
      inhibitory properties of the drug methotrexate (MTX) on dynamic viscosity of
      hyaluronan (HA) solutions in the same manner. METHODS: For in vitro testing of
      the inhibitory properties of CARN against degradation of HA solutions, we used
      the model of degradation of hyaluronan (HA) induced by free radicals. Both
      substances, CARN and MTX, were compared to glutathione (GSH). Rotational
      viscometry was used in evaluation of protective properties of compounds studied.
      The ability of CARN to restore the redox imbalance occurring in adjuvant
      arthritis (AA) of rats was also tested. We monitored the effect of CARN on hind
      paw volume (HPV) and on the levels of protein carbonyls, and thiobarbituric acid
      reacting substances (TBARS) in AA. RESULTS: In the reaction system with the
      prevalence of *OH and/or peroxy-type radicals, CARN in 200 MUmol/L concentration
      tested was shown to exert a protective action on HA degradation. MTX was less
      effective than CARN in preventing HA degradation. Its ability to protect HA
      against radical degradation was evident only at the highest concentration of 400
      MUmol/L. In AA, carnosine significantly reduced TBARS and protein carbonyls in
      plasma, and also decreased the HPV of animals most effectively on the day 14.
      CONCLUSIONS: CARN proved its inhibitory properties against degradation of HA
      solutions at experimental conditions in vitro and showed its beneficial
      efficiency in vivo. Moreover, it reduced also HPV, the clinical marker of
      inflammation in AA.

PMID- 21187838
TI  - Caco-2 cell monolayer integrity and effect of probiotic Escherichia coli Nissle
      1917 components.
AB  - OBJECTIVES: Different probiotic strains used in clinical trials have shown
      prophylactic properties in different inflammatory diseases of the
      gastrointestinal tract. This study was aimed to investigate the influence of
      Escherichia coli strain Nissle 1917 (EcN) components on the integrity of the Caco
      2 cell monolayer (human adenocarcinoma cell line). METHODS: The effect of
      supernatant of EcN suspension and lipopolysaccharide (LPS) isolated from EcN (in
      concentrations from 0.001 to 1 000 ug/ml) on paracellular transport of 14C
      mannitol marker through epithelial cell monolayer was estimated. RESULTS: Both
      LPS and EcN supernatant exerted almost the same effect; whereas no effect was
      shown using high concentrations (100 and 1 000 ug/ml), low concentrations (0.001,
      0.1 and 1 ug/ml) significantly decreased permeability of 14C-mannitol.
      Concentration (0.001 ug/ml) decreased 14C-mannitol permeability approximately
      about 20% (LPS) and 30% (EcN supernatant). To elucidate the observed changes in
      monolayer permeability ("tighter monolayer") induced by concentrations of LPS or
      supernatant, media able to open epithelial intercellular junctions were used. The
      effects of Ca2+-free transport medium and of medium containing 5, 10, 20, 50, and
      100% of Ca2+ on the 14C-mannitol transport in the presence of the lowest (0.001
      ug/ml) and high (100 ug/ml) concentrations of LPS were studied. Using Ca2+-free
      medium both concentrations of LPS significantly decreased apparent permeability
      coefficient (Papp) of 14C-mannitol indicating that changes of 14C-mannitol
      permeability are independent of dimensions of paracellular spaces. CONCLUSION:
      The decrease of 14C-mannitol permeability caused by EcN LPS indicates the ability
      of components of probiotic EcN strain to restore disrupted epithelial barrier.

PMID- 21187839
TI  - Ascorbate and Cu(II)-induced oxidative degradation of high-molar-mass hyaluronan.
      Pro- and antioxidative effects of some thiols.
AB  - OBJECTIVE: This study presents the results of antioxidative and pro-oxidative
      efficacy of cysteamine and D-penicillamine (D-pen) in comparison to L-glutathione
      (L-GSH) on high-molar-mass hyaluronan (HA) degradation by cupric ions plus
      ascorbic acid. METHODS: The substance tested was applied in the degradative
      system cupric ions plus ascorbate: (i) before the reaction onset or also (ii) 1 h
      after the reaction started. The results obtained were compared with that one
      recorded by using the degradative system in the absence of the substance tested.
      To monitor HA degradation kinetics, rotational viscometry was applied. Moreover,
      the standard ABTS and DPPH assays were used. RESULTS: By using the method of
      rotational viscometry, D-pen showed dual effect: initial inhibitory effect on *OH
      radicals was changed to a pro-oxidative one in the dose and time dependent
      manner. Both L-GSH and cysteamine were recorded to be more effective scavengers
      of *OH radicals than D-pen. Cysteamine demonstrated to be an excellent scavenger
      also of alkoxyl- and peroxyl- type radicals. Based on IC50 values, gained by ABTS
      assay, it is evident that D-pen showed higher radical scavenging capacity
      compared to cysteamine. Similar results were observed also in DPPH assay,
      although in this assay less effective radical scavenging capacities of both
      substances tested were recorded. CONCLUSIONS: On the basis of the results
      obtained, it can be stated that D-pen can produce hydrogen peroxide or *OH
      radicals and can inhibit the production of these oxidants. Our results showed
      that both L-GSH and cysteamine are similarly effective in inhibiting of HA
      degradation. Moreover, cysteamine demonstrated to be a significant inhibitor of
      alkoxyl- and peroxyl- type radicals generated from C-type macroradical of HA.

PMID- 21187841
TI  - Prevalence of infection with adenovirus-36 in Belgium and Holland and association
      with obesity.

PMID- 21187845
TI  - Shortsighted education reform.

PMID- 21187846
TI  - An RXR-gamma Rx for white-matter damage.

PMID- 21187847
TI  - Caspase activation without apoptosis: insight into Abeta initiation of
      neurodegeneration.

PMID- 21187848
TI  - Orphan nuclear receptors control neuronal remodeling during fly metamorphosis.

PMID- 21187851
TI  - The UK population: how does it compare?
AB  - This is the fourth demographic report for the UK, providing an overview of the
      latest statistics on the population. This year's article compares the UK with
      other European countries and a range of nations from around the world.
      Statistical comparisons are made for fertility, mortality, ageing, migration and
      population density. The UK has an ageing population, but one that is not ageing
      as rapidly as some other countries such as Germany, Italy and Japan. Although
      life expectation in the UK is improving in line with most western European
      countries, relatively high levels of fertility ensure that the proportion of the
      population that is young remains high. Around one in ten residents of the UK are
      foreign born, a lower proportion than many developed countries. UK population
      density has increased steadily and is the fourth highest in the EU.

PMID- 21187849
TI  - Endocannabinoid signaling in the brain: biosynthetic mechanisms in the limelight.
AB  - Studies of the endocannabinoid system in the CNS have been mostly focused on
      endocannabinoid receptors and inactivating mechanisms. Until recently, very
      little was known about the role of biosynthetic enzymes in endocannabinoid
      signaling. New data from the recent development of pharmacological and genetic
      tools for the study of these enzymes point to their fundamental role in
      determining where and when endocannabinoids function, and raise the possibility
      of new intriguing and previously unsuspected concepts in the general strategy of
      endocannabinoid signaling. However, even with these new tools, the cross-talk
      between anandamide and 2-arachidonoylglycerol biosynthesis makes it difficult to
      dissect one from the other, and data will need to be interpreted with this in
      mind.

PMID- 21187852
TI  - No vote--no census: an account of some of the events of 1910-1911.
AB  - The 2011 Census on the 27 March will be the latest in a series spanning over two
      centuries and covering vast demographic changes in the British population.
      Although the underlying aim of each census since 1801 has been to obtain an
      accurate enumeration of the population, successive censuses have adapted to
      changing social and technological circumstances, asking appropriate questions and
      using the best available technology to compile results. A century ago, the 1911
      Census represented a shift from earlier censuses in its use of machine
      tabulation. Despite this innovation, however, what is perhaps most interesting
      about 1911 is the social and political circumstances: the 1911 Census took place
      against the background of a threatened boycott by the suffragette movement. The
      article demonstrates how, though times change and technology moves on, a
      successful census was conducted despite the deeply sensitive political times.

PMID- 21187853
TI  - Older workers' withdrawal from the labour market 1991 to 2007: impact of socio
      demographic characteristics, health and household circumstances.
AB  - This article presents an analysis of the withdrawal from the labour market of
      older workers in England and Wales between 1991 and 1995 and in England between
      2002/03 and 2006/07. It examines the relationship between withdrawal from the
      labour market and demographic and socio-economic characteristics of older
      workers, their labour market status, health status, housing, household
      circumstances and caring commitments at the start of each period being
      considered.

PMID- 21187854
TI  - Changes in family structure in early childhood in the Millennium Cohort Study.
AB  - This article develops a typology of family change over the first five years of
      children's lives using data from the Millennium Cohort Study. It examines the
      changes over time of parental living arrangements and describes a range of
      social, economic and well-being indicators. It shows that nearly three quarters
      of this sample of young children have not experienced changes in family
      structures. The most advantaged group appears to be children living with
      continuously married parents, followed by those who live with cohabiting parents
      who marry. Children who experienced changes in family structure are a diverse
      group. Coupled parents who separate suffer the largest drop in income over five
      years. Lone parents who partner gain the most income. However, their incomes are
      still much lower than continuously partnered parents. This article suggests that
      using static or overly simplified measures of family structure hides important
      variations in the experiences of children.

PMID- 21187855
TI  - Nuclear initiated NF-kappaB signaling: NEMO and ATM take center stage.
AB  - A large body of literature describes elaborate NF-kappaB signaling networks
      induced by inflammatory and immune signals. Decades of research has revealed that
      transcriptionally functional NF-kappaB dimers are activated by two major
      pathways, canonical and non-canonical. Both pathways involve the release of NF
      kappaB dimers from inactive cytoplasmic complexes to cause their nuclear
      translocation to modulate gene expression programs and biological responses. NF
      kappaB is also responsive to genotoxic agents; however, signal communication
      networks that are initiated in the nucleus following DNA damage induction are
      less defined. Evidence in the literature supports the presence of such signaling
      pathways induced by multiple distinct genotoxic agents, resulting in the
      activation of cytoplasmic IKK complex. An example is a pathway that involves the
      DNA damage-responsive kinase ataxia telangiectasia mutated (ATM) and a series of
      post-translational modifications of NF-kappaB essential modulator (NEMO) in the
      nucleus of a genotoxin-exposed cell. Recent evidence also suggests that this
      nuclear-initiated NF-kappaB signaling pathway plays significant physiological and
      pathological roles, particularly in lymphocyte development and human cancer
      progression. This review will summarize these new developments, while identifying
      significant unanswered questions and providing new hypotheses that may be
      addressed in future studies.

PMID- 21187856
TI  - NF-kappaB signaling pathways regulated by CARMA family of scaffold proteins.
AB  - The NF-kappaB family of transcription factors plays a crucial role in cell
      activation, survival and proliferation. Its aberrant activity results in cancer,
      immunodeficiency or autoimmune disorders. Over the past two decades, tremendous
      progress has been made in our understanding of the signals that regulate NF
      kappaB activation, especially how scaffold proteins link different receptors to
      the NF-kappaB-activating complex, the IkappaB kinase complex. The growing number
      of these scaffolds underscores the complexity of the signaling networks in
      different cell types. In this review, we discuss the role of scaffold molecules
      in signaling cascades induced by stimulation of antigen receptors, G-protein
      coupled receptors and C-type Lectin receptors, resulting in NF-kappaB activation.
      Especially, we focus on the family of Caspase recruitment domain (CARD)
      containing proteins known as CARMA and their function in activation of NF-kappaB,
      as well as the link of these scaffolds to the development of various neoplastic
      diseases through regulation of NF-kappaB.

PMID- 21187857
TI  - The endoplasmic reticulum-associated degradation is necessary for plant salt
      tolerance.
AB  - Eukaryotic organisms have quality-control mechanisms that allow misfolded or
      unassembled proteins to be retained in the endoplasmic reticulum (ER) and
      subsequently degraded by ER-associated degradation (ERAD). The ERAD pathway is
      well studied in yeast and mammals; however, the biological functions of plant
      ERAD have not been reported. Through molecular and cellular biological
      approaches, we found that ERAD is necessary for plants to overcome salt stress.
      Upon salt treatment ubiquitinated proteins increased in plant cells, especially
      unfolded proteins that quickly accumulated in the ER and subsequently induced ER
      stress responses. Defect in HRD3A of the HRD1/HRD3 complex of the ERAD pathway
      resulted in alteration of the unfolded protein response (UPR), increased plant
      sensitivity to salt, and retention of ERAD substrates in plant cells.
      Furthermore, we demonstrated that Ca(2+) release from the ER is involved in the
      elevation of UPR and reactive oxygen species (ROS) participates the ERAD-related
      plant salt response pathway.

PMID- 21187858
TI  - NF-kappaB and STAT3 - key players in liver inflammation and cancer.
AB  - Hepatocellular carcinoma (HCC), the major form of primary liver cancer, is one of
      the most deadly human cancers. The pathogenesis of HCC is frequently linked with
      continuous hepatocyte death, inflammatory cell infiltration and compensatory
      liver regeneration. Understanding the molecular signaling pathways driving or
      mediating these processes during liver tumorigenesis is important for the
      identification of novel therapeutic targets for this dreadful disease. The
      classical IKKbeta-dependent NF-kappaB signaling pathway has been shown to promote
      hepatocyte survival in both developing and adult livers. In addition, it also
      plays a crucial role in liver inflammatory responses by controlling the
      expression of an array of growth factors and cytokines. One of these cytokines is
      IL-6, which is best known for its role in the liver acute phase response. IL-6
      exerts many of its functions via activation of STAT3, a transcription factor
      found to be important for HCC development. This review will focus on recent
      studies on the roles of NF-kappaB and STAT3 in liver cancer. Interactions between
      the two pathways and their potential as therapeutic targets will also be
      discussed.

PMID- 21187860
TI  - Mouse cloning and somatic cell reprogramming using electrofused blastomeres.
AB  - Mouse cloning from fertilized eggs can assist development of approaches for the
      production of "genetically tailored" human embryonic stem (ES) cell lines that
      are not constrained by the limitations of oocyte availability. However, to date
      only zygotes have been successfully used as recipients of nuclei from terminally
      differentiated somatic cell donors leading to ES cell lines. In fertility
      clinics, embryos of advanced embryonic stages are usually stored for future use,
      but their ability to support the derivation of ES cell lines via somatic nuclear
      transfer has not yet been proved. Here, we report that two-cell stage
      electrofused mouse embryos, arrested in mitosis, can support developmental
      reprogramming of nuclei from donor cells ranging from blastomeres to somatic
      cells. Live, full-term cloned pups from embryonic donors, as well as pluripotent
      ES cell lines from embryonic or somatic donors, were successfully generated from
      these reconstructed embryos. Advanced stage pre-implantation embryos were unable
      to develop normally to term after electrofusion and transfer of a somatic cell
      nucleus, indicating that discarded pre-implantation human embryos could be an
      important resource for research that minimizes the ethical concerns for human
      therapeutic cloning. Our approach provides an attractive and practical
      alternative to therapeutic cloning using donated oocytes for the generation of
      patient-specific human ES cell lines.

PMID- 21187859
TI  - Crosstalk of reactive oxygen species and NF-kappaB signaling.
AB  - NF-kappaB proteins are a family of transcription factors that are of central
      importance in inflammation and immunity. NF-kappaB also plays important roles in
      other processes, including development, cell growth and survival, and
      proliferation, and is involved in many pathological conditions. Reactive Oxygen
      Species (ROS) are created by a variety of cellular processes as part of cellular
      signaling events. While certain NF-kappaB-regulated genes play a major role in
      regulating the amount of ROS in the cell, ROS have various inhibitory or
      stimulatory roles in NF-kappaB signaling. Here we review the regulation of ROS
      levels by NF-kappaB targets and various ways in which ROS have been proposed to
      impact NF-kappaB signaling pathways.

PMID- 21187862
TI  - High-dose glucose-insulin-potassium has hemodynamic benefits and can improve
      cardiac remodeling in acute myocardial infarction treated with primary
      percutaneous coronary intervention: From a randomized controlled study.
AB  - OBJECTIVE: To evaluate the effects of high-dose glucose-insulin-potassium (GIK)
      solution on hemodynamics and cardiac remodeling in patients with acute myocardial
      infarction (AMI) treated with primary percutaneous coronary intervention (PCI).
      PATIENTS AND METHODS: We observed the changes in the hemodynamic parameters in 26
      patients with AMI. All patients received primary PCI before entering the study.
      All patients in the study were randomized into the GIK group (n = 14) or the
      control group (n = 12). Patients in the GIK group received high-dose GIK solution
      (25% glucose, 80 mmol/L KCl and 50 IU/L insulin; 1.5 ml/kg/h) over 24 h. Patients
      in the control group received standard therapy. We monitored the hemodynamic
      parameters at baseline and after 6 h, 12 h, 18 h and 24 h, respectively. Then, we
      followed-up the cardiac function with echocardiography after 7 days, 1 month and
      6 months. RESULTS: The basic clinical data was similar between the groups.
      Primary PCI was performed successfully in 25 patients. The two groups were
      indistinguishable in all factors measured. GIK solution did not have a
      deleterious effect on the hemodynamic parameters. The pulmonary capillary wedge
      pressure increased during the first 12-h period and then decreased smoothly (F =
      3.75, P = 0.02). The trends were similar between the two groups. The system
      vascular resistance index (SVRI) and pulmonary vascular resistance index (PVRI)
      decreased during the first 12 h in the GIK group but increased in the control
      group. The GIK solution significantly influenced SVRI (F = 4.71, P = 0.02). GIK
      solution improved the cardiac function measured by stroke volume (F = 4.11, P =
      0.03) and cardiac index (F = 4.40, P = 0.02). In the 6-month follow-up, GIK
      improved cardiac remodeling (left ventricular diastolic diameter: 49.2 +/- 2.89
      vs. 53.9 +/- 2.48, P < 0.001; left ventricular systolic diameter: 32.9 +/- 2.24
      vs. 35.9 +/- 2.78, P < 0.01). CONCLUSION: High-dose GIK solution had no adverse
      effects on the hemodynamics in AMI patients treated with primary PCI. It can
      improve cardiac function by lowering SVRI. In the 6-month follow-up, it improved
      cardiac remodeling.

PMID- 21187861
TI  - Evolution of bacterial phosphoglycerate mutases: non-homologous isofunctional
      enzymes undergoing gene losses, gains and lateral transfers.
AB  - BACKGROUND: The glycolytic phosphoglycerate mutases exist as non-homologous
      isofunctional enzymes (NISE) having independent evolutionary origins and no
      similarity in primary sequence, 3D structure, or catalytic mechanism. Cofactor
      dependent PGM (dPGM) requires 2,3-bisphosphoglycerate for activity; cofactor
      independent PGM (iPGM) does not. The PGM profile of any given bacterium is
      unpredictable and some organisms such as Escherichia coli encode both forms.
      METHODS/PRINCIPAL FINDINGS: To examine the distribution of PGM NISE throughout
      the Bacteria, and gain insight into the evolutionary processes that shape their
      phyletic profiles, we searched bacterial genome sequences for the presence of
      dPGM and iPGM. Both forms exhibited patchy distributions throughout the bacterial
      domain. Species within the same genus, or even strains of the same species,
      frequently differ in their PGM repertoire. The distribution is further
      complicated by the common occurrence of dPGM paralogs, while iPGM paralogs are
      rare. Larger genomes are more likely to accommodate PGM paralogs or both NISE
      forms. Lateral gene transfers have shaped the PGM profiles with intradomain and
      interdomain transfers apparent. Archaeal-type iPGM was identified in many
      bacteria, often as the sole PGM. To address the function of PGM NISE in an
      organism encoding both forms, we analyzed recombinant enzymes from E. coli. Both
      NISE were active mutases, but the specific activity of dPGM greatly exceeded that
      of iPGM, which showed highest activity in the presence of manganese. We created
      PGM null mutants in E. coli and discovered the DeltadPGM mutant grew slowly due
      to a delay in exiting stationary phase. Overexpression of dPGM or iPGM overcame
      this defect. CONCLUSIONS/SIGNIFICANCE: Our biochemical and genetic analyses in E.
      coli firmly establish dPGM and iPGM as NISE. Metabolic redundancy is indicated
      since only larger genomes encode both forms. Non-orthologous gene displacement
      can fully account for the non-uniform PGM distribution we report across the
      bacterial domain.

PMID- 21187863
TI  - Change of the aortic elasticity in rheumatoid arthritis: Relationship to
      associated cardiovascular risk factors.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory
      disease, which is associated with an excess of cardiovascular events. A decrease
      in the compliance of the arterial system, termed arterial stiffness, results in
      increased cardiac workload. Primary prevention of cardiovascular disease (CVD) is
      a priority for modern medicine. Therefore, further studies are required to
      explore the mechanisms through which CVD increases in RA. PATIENTS AND METHODS:
      This case-control study was performed to detect possible change of aortic
      elasticity in patients with RA, and to estimate the impact of different
      cardiovascular and atherogenic risk factors on the severity of arterial
      stiffness. Sixty-three consecutive adults with RA were enrolled for the study
      (case group). Forty-one healthy adults matched for age and gender were considered
      as a control group. All were subjected to assessment of aortic stiffness index
      and various cardiovascular risk factors. Patients with rheumatoid disease (case
      group) were divided by their aortic stiffness index status to two groups (A and
      B, with and without aortic stiffness, respectively). RESULTS: Aortic stiffness
      was present in 31.7% of the RA patients. Age of the patients, duration of RA,
      smoking index, waist circumference, triglycerides levels, and CRP were
      significantly higher in patients with aortic stiffness. CONCLUSION: RA is
      associated with decreased elasticity of the aorta in both genders, and such
      changes seem to be higher in the presence of visceral obesity, smoking, high
      triglycerides, and extraarticular disease severity.

PMID- 21187864
TI  - Silent myocardial ischemia in prediabetics in relation to insulin resistance.
AB  - BACKGROUND: Myocardial perfusion imaging (MPI) is a powerful diagnostic and
      prognostic tool for evaluating coronary artery disease (CAD). Several studies
      have shown Type 2 diabetics are at increased risk for having CAD. In addition,
      insulin resistance is generally considered to be of major importance in the
      pathophysiology of Type 2 diabetes mellitus. However, the area of screening
      prediabetics for CAD remains unclear. Given that glucose intolerance and insulin
      resistance precede the development of overt diabetes, these factors would be
      associated with CAD. AIM: This study was designed to evaluate the state of
      myocardial perfusion in prediabetic adults detected by single photon emission
      computed tomography (SPECT) in relation to insulin resistance. PATIENTS AND
      METHODS: A descriptive study was performed. Out of 113 consecutive prediabetic
      adults, 32 had insulin resistance (Group A) and 81 had insulin sensitivity (Group
      B). All were subjected to full medical history and clinical examination including
      blood pressure, waist circumference, and body mass index. Biochemical studies
      including lipids profile, fasting blood glucose, and homeostasis model
      assessments (HOMA) test. Exercise treadmill technetium (99mTC) sestamibi SPECT
      scintigraphy were done for assessment of myocardial perfusion assessed by summed
      difference score as well as occurrence of transient left ventricular dilatation.
      RESULTS: Significant increase in summed difference score as well as transient
      left ventricular dilatation was observed in Group A than Group B. It is
      correlated with insulin resistance, and the correlation appears to be independent
      of glucose tolerance status and obesity. Similar correlations were observed with
      age, triglycerides, and waist circumference. CONCLUSION: Prediabetics have
      myocardial perfusion defects which represent a pattern of cardiovascular risk.
      These are predominantly observed in prediabetics with increased HOMA IR and
      visceral obesity independent of glucose levels.

PMID- 21187865
TI  - Diagnosis and surgical treatment of carotid body tumor: A report of 18 cases.
AB  - OBJECTIVE: To summarize the experience in the diagnosis and treatment of carotid
      body tumor (CBT). MATERIALS AND METHODS: CBT in 18 cases was confirmed by digital
      subtraction angiography (DSA). Resection of the tumor under the carotid
      adventitial plane was performed in 10 cases, the tumor with the external carotid
      artery in five cases, and the tumor with the internal and external arteries at
      the same time in three cases. RESULTS: Neither death nor any major complications
      occurred in all the 18 cases. Our follow-up of the 18 patients revealed neither
      recurrence nor metastasis. CONCLUSION: DSA is the gold standard for the diagnosis
      of CBT. After confirmation, thorough preoperative examination, sufficient
      preoperative preparation, and correct surgical approaches can result in
      satisfactory surgical effects.

PMID- 21187866
TI  - Role of multidetector computed tomography in evaluating complications following
      endovascular repair of aortic aneurysm.
AB  - OBJECTIVE: To study the role of multidetector computed tomography (MDCT) in
      evaluating various complications following endovascular stenting of aortic
      aneurysms. MATERIALS AND METHODS: Over a period of 2 years (June 2005 to June
      2007), 50 patients with aortic aneurysm on computed tomography (CT) angiogram
      were prospectively studied. Images were acquired on a 64 slice multidetector row
      CT scanner (GE-LightSpeed VCT) after intravenous administration of nonionic
      iodinated contrast. Nineteen patients underwent endovascular stent-graft repair
      based on their medical and surgical risk factors. Stent-graft related
      complications were recorded by CT angiography and analyzed using descriptive
      statistics. RESULTS: Most common complication related to the endovascular stent
      graft placement was endoleak (44.4%), followed by puncture site hematoma (27.8%),
      thrombotic occlusion of a limb of the bifurcated stent graft, kinking of the
      stent-graft, and difficult catheterization with intimal tear in the common iliac
      artery were 5.6% each. Poststent diameter of the aneurysm was an important
      predictor of endoleaks. All the patients with either increase or no change in the
      aneurysm size had endoleaks. CONCLUSION: MDCT angiography is an important
      modality in identifying, describing, and following up the various complications
      following endovascular repair of aortic aneurysms, endoleaks being the most
      common complication. Decrease in the poststent diameter of the aneurysm suggested
      a good outcome.

PMID- 21187867
TI  - Association of metabolic syndrome with obesity measures, metabolic profiles, and
      intake of dietary fatty acids in people of Asian Indian origin.
AB  - OBJECTIVE: The present community-based cross-sectional study was aimed to examine
      the association of metabolic syndrome (MS) with obesity measures, metabolic
      profiles, and intake of dietary fatty acids in Asian Indian population. PATIENTS
      AND METHODS: A total of 350 adult (30 years and above) individuals (184 males and
      166 females) inhabiting in and around Kolkata, India participated in this study.
      MS was defined using the protocol specifically designed for Asian Indian
      population. RESULTS: The prevalence of MS in the study was 31.4%. The prevalence
      was significantly higher (P < 0.01) in females (48.2%) as compared to males
      (16.3%). It was observed that males without MS had significantly higher mean
      waist circumference (WC P < 0.05); waist-hip ratio (WHR; P < 0.001); triglyceride
      (TG; P < 0.05); very low density lipoprotein cholesterol (VLDLc; P < 0.05) and
      fasting blood glucose (FBG; P < 0.01) as compared to females without MS.
      Significant differences were also observed for dietary intake of total fatty
      acids (TFA; P < 0.001); saturated fatty acids (SFA; P < 0.001) and
      polyunsaturated fatty acids (PUFA; P < 0.001) between individuals with and
      without MS. However, no significant association was observed in individuals with
      MS after controlling for age and sex. On the other, WC and body mass index (BMI)
      had significant correlation with SFA: mono unsaturated fatty acids (MUFA; P <
      0.01) in individuals without MS even after controlling for age and sex.
      CONCLUSION: It seem reasonable to argue that while dealing with MS in Asian
      Indians, clinicians should consider obesity measures, metabolic profiles and
      dietary fatty acids simultaneously.

PMID- 21187868
TI  - Predictors of large volume paracantesis induced circulatory dysfunction in
      patients with massive hepatic ascites.
AB  - PURPOSE: In patients with massive ascites, large volume paracentesis may be
      associated with complications as circulatory dysfunction. Selection of
      appropriate patients might reduce such side effects. PATIENTS AND METHODS: Forty
      five patients known to have liver cirrhosis and presenting with massive ascites
      were included. There were 27 males and 18 females, with age (mean 51.2+10.64).
      All patients were subjected to full history, clinical examination, complete blood
      picture, prothrombin time, serum albumin, total plasma protein, serum bilirubin,
      serum creatinine, serum electrolytes and plasma renin activity measured by
      radioimmunoassay. Echocardiographic evaluation for cardiac output, pulmonary
      artery pressure, diastolic and systolic function before and after paracentesis.
      Large-volume paracentesis (LVP) ranging 8-18 liters with a mean 9.9 L was
      performed to all patients. Paracentesis induced circulatory dysfunction (PICD)
      was defined as increase in plasma renin activity (PRA) of more than 50% of
      pretreatment value to a level greater than 7.5ng /ml/ hour on the 6th day after
      paracentesis. RESULTS: The incidence of PICD in patients with massive hepatic
      ascites was 73.3% (87.5% with Dextran and 38.5% with albumin). There were no
      serious systemic or local side effects one week following LVP. Type of plasma
      expander and younger ages were the only independent predictors (odd ratio OR with
      95% confidence interval CI, 3.01<21.79<157.58 and 0.80<.88<.97 respectively)
      Gender and other clinical and laboratory parameters had no influence. Neither
      electrolytes levels nor hematocrite value had an influence. Ascitic patients
      showed higher heart rate and cardiac output and lower arterial pressure that was
      accentuated after LVP (P < 0.01). Echocardiographic diastolic function, A wave
      velocity and deceleration time of the E wave were markedly increased in cirrhotic
      patients with tense ascites and the E/A ratio was markedly reduced (0.9 +/- 0.3)
      but was not significantly affected by LVP. Ejection fraction had similar values
      of the normal patients with a tendency to increase after paracentesis. There were
      no changes in the left ventricular wall thickness. CONCLUSION: LVP is a safe and
      effective procedure for treatment of tense/refractory ascites. PICD is a
      frequently occurring silent complication following LVP. Salt free human albumin
      should be the plasma expander of choice especially if at least 8 liters are
      evacuated. Left ventricular diastolic function is altered in cirrhosis with tense
      ascites. This may represent an early stage of hepatic cardiomyopathy but was not
      affected by LVP and this was not reflected on the occurrence of PICD.

PMID- 21187869
TI  - Possible involvement of alpha1-adrenergic receptor and K(ATP) channels in
      cardioprotective effect of remote aortic preconditioning in isolated rat heart.
AB  - BACKGROUND: Remote preconditioning is a phenomenon in which brief episodes of
      ischemia and reperfusion to remote organs protect the target organ against
      sustained ischemia/reperfusion (I/R)-induced injury. Protective effects of remote
      aortic preconditioning (RAPC) are well established in the heart, but their
      mechanisms still remain to be elucidated. OBJECTIVE: This study has been designed
      to investigate the possible involvement of alpha-1-adrenergic receptor (AR) and
      K(ATP) channels in cardio-protective effect of RAPC in isolated rat heart.
      MATERIALS AND METHODS: Four episodes of ischemia and reperfusion, each comprising
      of 5 min occlusion and 5 min reperfusion, were used to produce RAPC. Isolated
      perfused rat heart was subjected to global ischemia for 30 min followed by
      reperfusion for 120 min. Coronary effluent was analyzed for LDH and CK-MB release
      to assess the degree of cardiac injury. Myocardial infarct size was estimated
      macroscopically using TTC staining. RESULTS: Phenylephrine (20 MU/kg i.p.), as
      alpha-1-AR agonist, was noted to produce RAPC-like cardio-protection. However,
      administration of glibenclamide concomitantly or prior to phenylephrine abolished
      cardioprotection. Moreover, prazocin (1 mg/kg. i.p), as alpha-1-AR antagonist and
      glibenclamide (1 mg/kg i.p), a K(ATP) channel blocker, abolished the
      cardioprotective effect of RAPC. CONCLUSION: These data provide the evidence that
      alpha-1-AR activation involved in cardioprotective effect of RAPC-mediated trough
      opening of K(ATP) channels.

PMID- 21187870
TI  - Polymorphisms of methylenetetrahydrofolate reductase gene as the genetic
      predispositions of coronary artery diseases in eastern India.
AB  - BACKGROUND: Gene-environment interaction is an important aspect in the
      development of coronary artery disease (CAD). The mutation (677C-T) of
      methylenetetrahydrofolate reductase (MTHFR) gene results in a decrease of the
      enzyme activity that leads to mild hyperhomocysteinemia. Elevated plasma level of
      homocysteine has been recognized as an independent risk factor for cardiovascular
      disease. A case-control study was designed to assess whether the prevalence of
      some MTHFR gene polymorphisms have any role in the development of CAD. MATERIALS
      AND METHODS: The study included unrelated 217 cases with CAD and 255 healthy
      controls. DNA was extracted from peripheral blood. MTHFR genotypes were
      identified by seeing the presence or absence of 677C->T mutation obtained by PCR
      followed by Hinf1 restriction digestion. Multiple logistic regression analysis
      was carried out to find association between studied genotypes and lifestyle as
      well as biochemical risk factors. RESULTS: The T allele was found to be
      associated with the disease. Significant associations were found with smoking,
      hypertension, diabetes, and family history of CAD. CONCLUSION: The results
      indicate that MTHFR 677C-T polymorphism has significant association with CADs in
      the population of eastern India.

PMID- 21187871
TI  - A colossal atrial myxoma.
AB  - Atrial myxomas are the most common benign primary tumor of the heart. These
      cardiac growths can masquerade as mitral stenosis and infective endocarditis. A
      35-year-old man presented with complaints of nonspecific symptoms. Echocardiogram
      revealed a large atrial myxoma occupying the left atrium. Excision revealed a 14
      * 8 * 6 cm3 tumor attached to a 4 * 3 * 2 cm3 stalk of septal tissue. We describe
      a giant left atrial myxoma. We were not able to find another myxoma as big as
      this one in the literature, so we are reporting it.

PMID- 21187872
TI  - Heart failure and oral bacteria: How could be prevented?

PMID- 21187873
TI  - Periodontal disease linked to cardiovascular disease.

PMID- 21187874
TI  - Preface to the third issue of Journal of Cardiovascular Disease Research.

PMID- 21187875
TI  - High density lipoproteins-based therapies for cardiovascular disease.
AB  - Atherosclerosis is the leading cause of death in developed countries. High
      density lipoproteins (HDL) cholesterol level correlates inversely with the risk
      of cardiovascular diseases. Thus, HDL has obtained lots of interest for drug
      development. In this review, we summarized the mechanisms for the antiatherogenic
      function of HDL, current HDL-based drugs in clinical use and the future direction
      for HDL-based therapy development.

PMID- 21187876
TI  - Plasmacytoma of tonsil diagnosed by fine-needle aspiration cytology.
AB  - Extramedullary plasmacytoma of tonsil is rare. Even though biopsy is necessary
      for final diagnosis, fine-needle aspiration cytology (FNAC) can provide useful
      information in the management of such cases. We report a case of plasmacytoma of
      tonsil diagnosed by FNAC in a 43-year-old man who presented with a swelling in
      the right tonsillar area. FNAC smears revealed sheets of plasma cells at various
      stages of maturation. Subsequent histopathological and immunohistochemical
      studies confirmed the diagnosis of plasmacytoma. This case is reported for the
      rarity of site for extramedullary plasmacytoma and to highlight the usefulness of
      FNAC in lesions of tonsil.

PMID- 21187877
TI  - Cytodiagnosis of glomus tumor.
AB  - Glomus tumors are uncommon, with an estimated incidence of 1.6%. Cytological
      descriptions of this tumor are few. We report a 15-year-old boy presenting with a
      painful subungual swelling. Fine needle aspiration cytology showed uniform cells
      with homogeneous chromatin and scanty cytoplasm. Cytology was reported as
      "suggestive of glomus tumor". Histopathological examination confirmed the
      diagnosis. Careful cytomorphological examination supported by appropriate
      clinical history should suggest the diagnosis of glomus tumor and help in
      preoperative diagnosis.

PMID- 21187878
TI  - Scar endometriosis.
AB  - Endometriosis is the presence of functioning endometrium outside the uterus.
      Endometriosis rarely occurs in the abdominal wall. Majority of abdominal wall
      endometriosis occur in or adjacent to surgical scars, following caesarean section
      or hysterectomy. Laparotomy scar endometriosis following salpingectomy for
      ectopic pregnancy has rarely been reported. We report a case of scar
      endometriosis following laparotomy for chronic ectopic, and diagnosed by fine
      needle aspiration cytology (FNAC). Excision biopsy confirmed the FNAC diagnosis
      of scar endometriosis.

PMID- 21187879
TI  - Aggressive digital papillary adenocarcinoma diagnosed by fine needle aspiration
      cytology.
AB  - Aggressive digital papillary adenocarcinoma is a rare variant of eccrine sweat
      gland malignancy with a propensity for metastases and recurrence. We report a 45
      year-old female with aggressive digital papillary adenocarcinoma diagnosed by
      fine needle aspiration cytology (FNAC). The cytological findings were
      representative of the histological features. The recognition of aggressive
      digital papillary adenocarcinoma as a distinct clinicopathological eccrine sweat
      gland neoplasm is important because of the potential for aggressive local growth
      and distant metastasis. FNAC plays an important role in the preoperative
      diagnosis and management of these lesions.

PMID- 21187880
TI  - Burkitts lymphoma of the small intestine: A cytological diagnosis.

PMID- 21187881
TI  - Squash preparation: A reliable diagnostic tool in the intraoperative diagnosis of
      central nervous system tumors.
AB  - BACKGROUND: Intraoperative cytology is an important diagnostic modality improving
      on the accuracy of the frozen sections. It has shown to play an important role
      especially in the intraoperative diagnosis of central nervous system tumors. AIM:
      To study the diagnostic accuracy of squash preparation and frozen section (FS) in
      the intraoperative diagnosis of central nervous system (CNS) tumors. MATERIALS
      AND METHODS: This prospective study of 114 patients with CNS tumors was conducted
      over a period of 18 months (September 2004 to February 2006). The cytological
      preparations were stained by the quick Papanicolaou method. The squash
      interpretation and FS diagnosis were later compared with the paraffin section
      diagnosis. RESULTS: Of the 114 patients, cytological diagnosis was offered in 96
      cases. Eighteen nonneoplastic or noncontributory cases were excluded. Using
      hematoxylin and eosin-stained histopathology sections as the gold standard, the
      diagnostic accuracy of cytology was 88.5% (85/96) and the accuracy on FS
      diagnosis was 90.6% (87/96). Among these cases, gliomas formed the largest
      category of tumors (55.2%). The cytological accuracy in this group was 84.9%
      (45/53) and the comparative FS figure was 86.8% (46/53). In cases where the smear
      and the FS diagnosis did not match, the latter opinion was offered. CONCLUSIONS:
      Squash preparation is a reliable, rapid and easy method and can be used as a
      complement to FS in the intraoperative diagnosis of CNS tumors.

PMID- 21187882
TI  - Role of scrape cytology in the intraoperative diagnosis of tumor.
AB  - BACKGROUND: Rapid diagnosis of surgically removed specimens has created many
      controversies and a single completely reliable method has not yet been developed.
      Histopathology of a paraffin section remains the ultimate gold standard in tissue
      diagnosis. Frozen section is routinely used by the surgical pathology
      laboratories for intraoperative diagnosis. The use of either frozen section or
      cytological examination alone has an acceptable rate (93-97%) of correct
      diagnosis, with regard to interpretation of benign versus malignant. AIM: To
      evaluate the utility of scrape cytology for the rapid diagnosis of surgically
      removed tumors and its utilisation for learning cytopathology. MATERIALS AND
      METHODS: 75 surgically removed specimens from various organs and systems were
      studied. Scrapings were taken from each specimen before formalin fixation and
      stained by modified rapid Papanicolaou staining. RESULTS: Of the 75 cases
      studied, 73 could be correctly differentiated into benign and malignant tumors,
      with an accuracy rate of 97.3%. CONCLUSIONS: Intraoperative scrape cytology is
      useful for intraoperative diagnosis of tumor, where facilities for frozen section
      are not available. The skill and expertise developed by routinely practicing
      intraoperative cytology can be applied to the interpretation of fine needle
      aspirate smears. Thus, apart from its diagnostic role, intraoperative cytology
      can become a very useful learning tool in the field of cytopathology.

PMID- 21187884
TI  - Cytodiagnosis of chondromyxoid fibroma.
AB  - Chondromyxoid fibroma (CMF) is an unusual tumor that predominantly affects long
      bones of young adults. We present two cases of CMF that were diagnosed on
      cytology. The specific cytological features included varying combinations of
      chondroid, myxoid and fibroid elements. These features when correlated with
      clinico-radiological findings helped to arrive at a correct diagnosis. Thus a
      definitive diagnosis of CMF can be made on cytology based on which further line
      of treatment can be planned.

PMID- 21187883
TI  - Image-guided fine-needle aspiration cytology of ovarian tumors: An assessment of
      diagnostic efficacy.
AB  - BACKGROUND: Image-guided fine-needle aspiration cytology (FNAC) of ovarian lumps
      is being increasingly used for the successful diagnosis of ovarian tumors,
      although borderline cases may be difficult to diagnose by this method. AIM: To
      demonstrate the efficacy of image-guided FNAC in diagnosing ovarian tumors
      (benign and malignant) and to evaluate the usefulness of cytology as a mode of
      easy and rapid diagnosis of ovarian lumps. MATERIALS AND METHODS: The study was
      conducted on 42 female patients. Clinical evaluation and relevant investigations
      were carried out. Diagnosis was established by FNAC performed under image
      guidance (ultrasonography/computed tomography). The cytological diagnosis was
      confirmed by histopathological examination. RESULTS: Cytological diagnosis was
      rendered on all the 42 ovarian lesions, with a correct diagnosis in 34 cases,
      resulting in a diagnostic accuracy of 80.9%. Most of the cases with discordant
      diagnoses were surface epithelial tumors of low malignant potential and required
      histopathological examination for a final diagnosis. CONCLUSIONS: Image-guided
      FNAC is an inexpensive, rapid and fairly accurate procedure for the diagnosis of
      ovarian lesions. It provides a safe alternative to the more expensive, time
      consuming and cumbersome surgical route to diagnosis.

PMID- 21187885
TI  - The cytology of giant solitary trichoepithelioma.
AB  - Giant solitary trichoepithelioma (GST) is a rare trichogenic tumor, which may
      present as a pigmented lesion. An 80-year-old man was diagnosed to have giant
      solitary trichoepithelioma on fine-needle aspiration cytology. The cytological
      findings represented the histological features. The recognition of GST is
      important because of its close resemblance to basal cell carcinoma and other skin
      adnexal tumors - clinically, cytologically and histologically.

PMID- 21187886
TI  - Guest Editor's Message.

PMID- 21187887
TI  - Surgery for hernia: quo vadis?

PMID- 21187888
TI  - Sir Ganga Ram Hospital classification of groin and ventral abdominal wall
      hernias.
AB  - BACKGROUND: Numerous classifications for groin and ventral hernias have been
      proposed over the past five to six decades. The old, simple classification of
      groin hernia in to direct, inguinal and femoral components is no longer adequate
      to understand the complex pathophysiology and management of these hernias. The
      most commonly followed classification for ventral hernias divide them into
      congenital, acquired, incisional and traumatic, which also does not convey any
      information regarding the predicted level of difficulty. AIM: All the previous
      classification systems were based on open hernia repairs and have their own
      fallacies particularly for uncommon hernias that cannot be classified in these
      systems. With the advent of laparoscopic/ endoscopic approach, surgical access to
      the hernia as well as the functional anatomy viewed by the surgeon changed. This
      change in the surgical approach and functional anatomy opened the doors for newer
      classifications. The authors have thus proposed a classification system based on
      the expected level of intraoperative difficulty for endoscopic hernia repair.
      CLASSIFICATION: In the proposed classification higher grades signify increasing
      levels of expected intraoperative difficulty. This functional classification
      grades groin hernias according to the: a) Pre -operative predictive level of
      difficulty of endoscopic surgery, and b) Intraoperative factors that lead to a
      difficult repair. Pre operative factors include multiple or pantaloon hernias,
      recurrent hernias, irreducible and incarcerated hernias. Intraoperative factors
      include reducibility at operation, degree of descent of the hernial sac and
      previous hernia repairs. Hernial defects greater than 7 cm in diameter are
      categorized one grade higher. CONCLUSION: Though there have been several
      classification systems for groin or inguinal hernias, none have been described
      for total classification of all ventral hernias of the abdomen. The system
      proposed by us includes all abdominal wall hernias and is a final classification
      that predicts the expected level of difficulty for an endoscopic hernia repair.

PMID- 21187889
TI  - Evaluation of various prosthetic materials and newer meshes for hernia repairs.
AB  - The use of prosthesis has become essential for repair of all hernias since the
      recurrence rates are consistently lower when they are used. To fulfill this
      requirement, a variety of newer meshes have been engineered. An ideal prosthesis
      should be strong, pliable, non-allergenic, inert, non-biodegradable, non
      carcinogenic and should stimulate adequate fibroblastic activity for optimum
      incorporation into the tissues. Prosthesis used for hernia repairs can be non
      absorbable, composite (combination of absorbable and non-absorbable fibres) or
      with an absorbable or a non-absorbable barrier. Surgeons should acquire
      sufficient knowledge of different types of prosthesis so as to select an
      appropriate one for a given case. Non-absorbable or composite mesh is recommended
      for hernia repair where it will not come in contact with the bowel. Prosthesis
      with a barrier only should be used for intra-abdominal placement to prevent bowel
      adhesions since it is increasingly difficult to defend the use of a biomaterial
      that has no adhesion barriers. This review highlghts all these different types of
      meshes and their appropriate selection for a given hernia repair. Selection of
      the optimum size and its proper fixation is mandaory. Complications can be
      avoided or minimized with proper selection of mesh for a given case and by
      performing the surgery with a meticulous technique.

PMID- 21187890
TI  - Extravascular lung water correlates multiorgan dysfunction syndrome and mortality
      in sepsis.
AB  - BACKGROUND: This study was designated to investigate whether increased
      extravascular lung water index (EVLWI) may correlate multiple organ dysfunction
      syndrome (MODS) and mortality in sepsis. METHODS: We designed a prospective
      cohort study in an intensive care unit of a tertiary care hospital. Sixty-seven
      patients with severe sepsis were included. Data were used to determine an
      association between EVLWI and the development of MODS and mortality. These
      connections were determined by the multiple logistic regression, plotting the
      receiver operating characteristic (ROC) curve and by Spearman test. RESULTS:
      EVLWI levels were higher in MODS patients on day 1 (median (IQR), 18(12.8-23.9)
      ml/kg, n = 38, p<0.0001) than in those without (median (IQR), 12.4 (7.9-16.3)
      ml/kg, n = 29) and day 3 (median (IQR), 17.8 (11.2-22.8) ml/kg, n = 29, p =
      0.004) than in those without (median (IQR), 12.4 (8.0-16.3) ml/kg, n = 29). EVLWI
      was used as an independent predictor of the development of MODS (odds ratio, 1.6;
      p = 0.005; 95% confidence interval, 1.2~2.2) during ICU stay. The area under the
      ROC curve showed that EVLWI levels could predict MODS (0.866) and mortality
      (0.881) during ICU stay. Meanwhile, the higher of SOFA score, the more EVLWI was
      found on day 1 (r = 0.7041, p<0.0001) and day 3 (r = 0.7732, p<0.0001).
      CONCLUSIONS: Increased EVLWI levels correlates development of MODS and mortality
      during the patients' ICU stay. Further more, the potential of novel treatment in
      severe sepsis with lung injury may develop.

PMID- 21187891
TI  - Identifying the age cohort responsible for transmission in a natural outbreak of
      Bordetella bronchiseptica.
AB  - Identifying the major routes of disease transmission and reservoirs of infection
      are needed to increase our understanding of disease dynamics and improve disease
      control. Despite this, transmission events are rarely observed directly. Here we
      had the unique opportunity to study natural transmission of Bordetella
      bronchiseptica--a directly transmitted respiratory pathogen with a wide mammalian
      host range, including sporadic infection of humans--within a commercial rabbitry
      to evaluate the relative effects of sex and age on the transmission dynamics
      therein. We did this by developing an a priori set of hypotheses outlining how
      natural B. bronchiseptica infections may be transmitted between rabbits. We
      discriminated between these hypotheses by using force-of-infection estimates
      coupled with random effects binomial regression analysis of B. bronchiseptica age
      prevalence data from within our rabbit population. Force-of-infection analysis
      allowed us to quantify the apparent prevalence of B. bronchiseptica while
      correcting for age structure. To determine whether transmission is largely within
      social groups (in this case litter), or from an external group, we used random
      effect binomial regression to evaluate the importance of social mixing in disease
      spread. Between these two approaches our results support young weanlings--as
      opposed to, for example, breeder or maternal cohorts--as the age cohort primarily
      responsible for B. bronchiseptica transmission. Thus age-prevalence data, which
      is relatively easy to gather in clinical or agricultural settings, can be used to
      evaluate contact patterns and infer the likely age-cohort responsible for
      transmission of directly transmitted infections. These insights shed light on the
      dynamics of disease spread and allow an assessment to be made of the best methods
      for effective long-term disease control.

PMID- 21187892
TI  - H2A.Z demarcates intergenic regions of the plasmodium falciparum epigenome that
      are dynamically marked by H3K9ac and H3K4me3.
AB  - Epigenetic regulatory mechanisms and their enzymes are promising targets for
      malaria therapeutic intervention; however, the epigenetic component of gene
      expression in P. falciparum is poorly understood. Dynamic or stable association
      of epigenetic marks with genomic features provides important clues about their
      function and helps to understand how histone variants/modifications are used for
      indexing the Plasmodium epigenome. We describe a novel, linear amplification
      method for next-generation sequencing (NGS) that allows unbiased analysis of the
      extremely AT-rich Plasmodium genome. We used this method for high resolution,
      genome-wide analysis of a histone H2A variant, H2A.Z and two histone H3 marks
      throughout parasite intraerythrocytic development. Unlike in other organisms,
      H2A.Z is a constant, ubiquitous feature of euchromatic intergenic regions
      throughout the intraerythrocytic cycle. The almost perfect colocalisation of
      H2A.Z with H3K9ac and H3K4me3 suggests that these marks are preferentially
      deposited on H2A.Z-containing nucleosomes. By performing RNA-seq on 8 time
      points, we show that acetylation of H3K9 at promoter regions correlates very well
      with the transcriptional status whereas H3K4me3 appears to have stage-specific
      regulation, being low at early stages, peaking at trophozoite stage, but does not
      closely follow changes in gene expression. Our improved NGS library preparation
      procedure provides a foundation to exploit the malaria epigenome in detail.
      Furthermore, our findings place H2A.Z at the cradle of P. falciparum epigenetic
      regulation by stably defining intergenic regions and providing a platform for
      dynamic assembly of epigenetic and other transcription related complexes.

PMID- 21187893
TI  - Noise cancellation: viral fine tuning of the cellular environment for its own
      genome replication.
AB  - Productive replication of DNA viruses elicits host cell DNA damage responses,
      which cause both beneficial and detrimental effects on viral replication. In
      response to the viral productive replication, host cells attempt to attenuate the
      S-phase cyclin-dependent kinase (CDK) activities to inhibit viral replication.
      However, accumulating evidence regarding interactions between viral factors and
      cellular signaling molecules indicate that viruses utilize them and selectively
      block the downstream signaling pathways that lead to attenuation of the high S
      phase CDK activities required for viral replication. In this review, we describe
      the sophisticated strategy of Epstein-Barr virus to cancel such "noisy" host
      defense signals in order to hijack the cellular environment.

PMID- 21187894
TI  - Dimeric 2G12 as a potent protection against HIV-1.
AB  - We previously showed that broadly neutralizing anti-HIV-1 antibody 2G12 (human
      IgG1) naturally forms dimers that are more potent than monomeric 2G12 in in vitro
      neutralization of various strains of HIV-1. In this study, we have investigated
      the protective effects of monomeric versus dimeric 2G12 against HIV-1 infection
      in vivo using a humanized mouse model. Our results showed that passively
      transferred, purified 2G12 dimer is more potent than 2G12 monomer at preventing
      CD4 T cell loss and suppressing the increase of viral load following HIV-1
      infection of humanized mice. Using humanized mice bearing IgG "backpack" tumors
      that provided 2G12 antibodies continuously, we found that a sustained dimer
      concentration of 5-25 ug/ml during the course of infection provides effective
      protection against HIV-1. Importantly, 2G12 dimer at this concentration does not
      favor mutations of the HIV-1 envelope that would cause the virus to completely
      escape 2G12 neutralization. We have therefore identified dimeric 2G12 as a potent
      prophylactic reagent against HIV-1 in vivo, which could be used as part of an
      antibody cocktail to prevent HIV-1 infection.

PMID- 21187895
TI  - A quantitative systems approach reveals dynamic control of tRNA modifications
      during cellular stress.
AB  - Decades of study have revealed more than 100 ribonucleoside structures
      incorporated as post-transcriptional modifications mainly in tRNA and rRNA, yet
      the larger functional dynamics of this conserved system are unclear. To this end,
      we developed a highly precise mass spectrometric method to quantify tRNA
      modifications in Saccharomyces cerevisiae. Our approach revealed several novel
      biosynthetic pathways for RNA modifications and led to the discovery of signature
      changes in the spectrum of tRNA modifications in the damage response to
      mechanistically different toxicants. This is illustrated with the RNA
      modifications Cm, m(5)C, and m(2) (2)G, which increase following hydrogen
      peroxide exposure but decrease or are unaffected by exposure to methylmethane
      sulfonate, arsenite, and hypochlorite. Cytotoxic hypersensitivity to hydrogen
      peroxide is conferred by loss of enzymes catalyzing the formation of Cm, m(5)C,
      and m(2) (2)G, which demonstrates that tRNA modifications are critical features
      of the cellular stress response. The results of our study support a general model
      of dynamic control of tRNA modifications in cellular response pathways and add to
      the growing repertoire of mechanisms controlling translational responses in
      cells.

PMID- 21187896
TI  - Modeling the evolution of regulatory elements by simultaneous detection and
      alignment with phylogenetic pair HMMs.
AB  - The computational detection of regulatory elements in DNA is a difficult but
      important problem impacting our progress in understanding the complex nature of
      eukaryotic gene regulation. Attempts to utilize cross-species conservation for
      this task have been hampered both by evolutionary changes of functional sites and
      poor performance of general-purpose alignment programs when applied to non-coding
      sequence. We describe a new and flexible framework for modeling binding site
      evolution in multiple related genomes, based on phylogenetic pair hidden Markov
      models which explicitly model the gain and loss of binding sites along a
      phylogeny. We demonstrate the value of this framework for both the alignment of
      regulatory regions and the inference of precise binding-site locations within
      those regions. As the underlying formalism is a stochastic, generative model, it
      can also be used to simulate the evolution of regulatory elements. Our
      implementation is scalable in terms of numbers of species and sequence lengths
      and can produce alignments and binding-site predictions with accuracy rivaling or
      exceeding current systems that specialize in only alignment or only binding-site
      prediction. We demonstrate the validity and power of various model components on
      extensive simulations of realistic sequence data and apply a specific model to
      study Drosophila enhancers in as many as ten related genomes and in the presence
      of gain and loss of binding sites. Different models and modeling assumptions can
      be easily specified, thus providing an invaluable tool for the exploration of
      biological hypotheses that can drive improvements in our understanding of the
      mechanisms and evolution of gene regulation.

PMID- 21187897
TI  - HIV-1 envelope subregion length variation during disease progression.
AB  - The V3 loop of the HIV-1 Env protein is the primary determinant of viral
      coreceptor usage, whereas the V1V2 loop region is thought to influence coreceptor
      binding and participate in shielding of neutralization-sensitive regions of the
      Env glycoprotein gp120 from antibody responses. The functional properties and
      antigenicity of V1V2 are influenced by changes in amino acid sequence, sequence
      length and patterns of N-linked glycosylation. However, how these polymorphisms
      relate to HIV pathogenesis is not fully understood. We examined 5185 HIV-1 gp120
      nucleotide sequence fragments and clinical data from 154 individuals (152 were
      infected with HIV-1 Subtype B). Sequences were aligned, translated, manually
      edited and separated into V1V2, C2, V3, C3, V4, C4 and V5 subregions. V1-V5 and
      subregion lengths were calculated, and potential N-linked glycosylation sites
      (PNLGS) counted. Loop lengths and PNLGS were examined as a function of time since
      infection, CD4 count, viral load, and calendar year in cross-sectional and
      longitudinal analyses. V1V2 length and PNLGS increased significantly through
      chronic infection before declining in late-stage infection. In cross-sectional
      analyses, V1V2 length also increased by calendar year between 1984 and 2004 in
      subjects with early and mid-stage illness. Our observations suggest that there is
      little selection for loop length at the time of transmission; following
      infection, HIV-1 adapts to host immune responses through increased V1V2 length
      and/or addition of carbohydrate moieties at N-linked glycosylation sites. V1V2
      shortening during early and late-stage infection may reflect ineffective host
      immunity. Transmission from donors with chronic illness may have caused the
      modest increase in V1V2 length observed during the course of the pandemic.

PMID- 21187898
TI  - An ABC transporter mutation is correlated with insect resistance to Bacillus
      thuringiensis Cry1Ac toxin.
AB  - Transgenic crops producing insecticidal toxins from Bacillus thuringiensis (Bt)
      are commercially successful in reducing pest damage, yet knowledge of resistance
      mechanisms that threaten their sustainability is incomplete. Insect resistance to
      the pore-forming Cry1Ac toxin is correlated with the loss of high-affinity,
      irreversible binding to the mid-gut membrane, but the genetic factors responsible
      for this change have been elusive. Mutations in a 12-cadherin-domain protein
      confer some Cry1Ac resistance but do not block this toxin binding in in vitro
      assays. We sought to identify mutations in other genes that might be responsible
      for the loss of binding. We employed a map-based cloning approach using a series
      of backcrosses with 1,060 progeny to identify a resistance gene in the cotton
      pest Heliothis virescens that segregated independently from the cadherin
      mutation. We found an inactivating mutation of the ABC transporter ABCC2 that is
      genetically linked to Cry1Ac resistance and is correlated with loss of Cry1Ac
      binding to membrane vesicles. ABC proteins are integral membrane proteins with
      many functions, including export of toxic molecules from the cell, but have not
      been implicated in the mode of action of Bt toxins before. The reduction in toxin
      binding due to the inactivating mutation suggests that ABCC2 is involved in
      membrane integration of the toxin pore. Our findings suggest that ABC proteins
      may play a key role in the mode of action of Bt toxins and that ABC protein
      mutations can confer high levels of resistance that could threaten the continued
      utilization of Bt-expressing crops. However, such mutations may impose a
      physiological cost on resistant insects, by reducing export of other toxins such
      as plant secondary compounds from the cell. This weakness could be exploited to
      manage this mechanism of Bt resistance in the field.

PMID- 21187899
TI  - Encoding of spatio-temporal input characteristics by a CA1 pyramidal neuron
      model.
AB  - The in vivo activity of CA1 pyramidal neurons alternates between regular spiking
      and bursting, but how these changes affect information processing remains
      unclear. Using a detailed CA1 pyramidal neuron model, we investigate how timing
      and spatial arrangement variations in synaptic inputs to the distal and proximal
      dendritic layers influence the information content of model responses. We find
      that the temporal delay between activation of the two layers acts as a switch
      between excitability modes: short delays induce bursting while long delays
      decrease firing. For long delays, the average firing frequency of the model
      response discriminates spatially clustered from diffused inputs to the distal
      dendritic tree. For short delays, the onset latency and inter-spike-interval
      succession of model responses can accurately classify input signals as temporally
      close or distant and spatially clustered or diffused across different stimulation
      protocols. These findings suggest that a CA1 pyramidal neuron may be capable of
      encoding and transmitting presynaptic spatiotemporal information about the
      activity of the entorhinal cortex-hippocampal network to higher brain regions via
      the selective use of either a temporal or a rate code.

PMID- 21187900
TI  - How noisy adaptation of neurons shapes interspike interval histograms and
      correlations.
AB  - Channel noise is the dominant intrinsic noise source of neurons causing
      variability in the timing of action potentials and interspike intervals (ISI).
      Slow adaptation currents are observed in many cells and strongly shape response
      properties of neurons. These currents are mediated by finite populations of ionic
      channels and may thus carry a substantial noise component. Here we study the
      effect of such adaptation noise on the ISI statistics of an integrate-and-fire
      model neuron by means of analytical techniques and extensive numerical
      simulations. We contrast this stochastic adaptation with the commonly studied
      case of a fast fluctuating current noise and a deterministic adaptation current
      (corresponding to an infinite population of adaptation channels). We derive
      analytical approximations for the ISI density and ISI serial correlation
      coefficient for both cases. For fast fluctuations and deterministic adaptation,
      the ISI density is well approximated by an inverse Gaussian (IG) and the ISI
      correlations are negative. In marked contrast, for stochastic adaptation, the
      density is more peaked and has a heavier tail than an IG density and the serial
      correlations are positive. A numerical study of the mixed case where both fast
      fluctuations and adaptation channel noise are present reveals a smooth transition
      between the analytically tractable limiting cases. Our conclusions are
      furthermore supported by numerical simulations of a biophysically more realistic
      Hodgkin-Huxley type model. Our results could be used to infer the dominant source
      of noise in neurons from their ISI statistics.

PMID- 21187901
TI  - Glacial refugia in pathogens: European genetic structure of anther smut pathogens
      on Silene latifolia and Silene dioica.
AB  - Climate warming is predicted to increase the frequency of invasions by pathogens
      and to cause the large-scale redistribution of native host species, with dramatic
      consequences on the health of domesticated and wild populations of plants and
      animals. The study of historic range shifts in response to climate change, such
      as during interglacial cycles, can help in the prediction of the routes and
      dynamics of infectious diseases during the impending ecosystem changes. Here we
      studied the population structure in Europe of two Microbotryum species causing
      anther smut disease on the plants Silene latifolia and Silene dioica. Clustering
      analyses revealed the existence of genetically distinct groups for the pathogen
      on S. latifolia, providing a clear-cut example of European phylogeography
      reflecting recolonization from southern refugia after glaciation. The pathogen
      genetic structure was congruent with the genetic structure of its host species S.
      latifolia, suggesting dependence of the migration pathway of the anther smut
      fungus on its host. The fungus, however, appeared to have persisted in more
      numerous and smaller refugia than its host and to have experienced fewer events
      of large-scale dispersal. The anther smut pathogen on S. dioica also showed a
      strong phylogeographic structure that might be related to more northern glacial
      refugia. Differences in host ecology probably played a role in these differences
      in the pathogen population structure. Very high selfing rates were inferred in
      both fungal species, explaining the low levels of admixture between the genetic
      clusters. The systems studied here indicate that migration patterns caused by
      climate change can be expected to include pathogen invasions that follow the
      redistribution of their host species at continental scales, but also that the
      recolonization by pathogens is not simply a mirror of their hosts, even for
      obligate biotrophs, and that the ecology of hosts and pathogen mating systems
      likely affects recolonization patterns.

PMID- 21187902
TI  - Functional comparison of innate immune signaling pathways in primates.
AB  - Humans respond differently than other primates to a large number of infections.
      Differences in susceptibility to infectious agents between humans and other
      primates are probably due to inter-species differences in immune response to
      infection. Consistent with that notion, genes involved in immunity-related
      processes are strongly enriched among recent targets of positive selection in
      primates, suggesting that immune responses evolve rapidly, yet providing only
      indirect evidence for possible inter-species functional differences. To directly
      compare immune responses among primates, we stimulated primary monocytes from
      humans, chimpanzees, and rhesus macaques with lipopolysaccharide (LPS) and
      studied the ensuing time-course regulatory responses. We find that, while the
      universal Toll-like receptor response is mostly conserved across primates, the
      regulatory response associated with viral infections is often lineage-specific,
      probably reflecting rapid host-virus mutual adaptation cycles. Additionally,
      human-specific immune responses are enriched for genes involved in apoptosis, as
      well as for genes associated with cancer and with susceptibility to infectious
      diseases or immune-related disorders. Finally, we find that chimpanzee-specific
      immune signaling pathways are enriched for HIV-interacting genes. Put together,
      our observations lend strong support to the notion that lineage-specific immune
      responses may help explain known inter-species differences in susceptibility to
      infectious diseases.

PMID- 21187904
TI  - NleC, a type III secretion protease, compromises NF-kappaB activation by
      targeting p65/RelA.
AB  - The NF-kappaB signaling pathway is central to the innate and adaptive immune
      responses. Upon their detection of pathogen-associated molecular patterns, Toll
      like receptors on the cell surface initiate signal transduction and activate the
      NF-kappaB pathway, leading to the production of a wide array of inflammatory
      cytokines, in attempt to eradicate the invaders. As a countermeasure, pathogens
      have evolved ways to subvert and manipulate this system to their advantage.
      Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC) are
      closely related bacteria responsible for major food-borne diseases worldwide. Via
      a needle-like protein complex called the type three secretion system (T3SS),
      these pathogens deliver virulence factors directly to host cells and modify
      cellular functions, including by suppressing the inflammatory response. Using
      gain- and loss-of-function screenings, we identified two bacterial effectors,
      NleC and NleE, that down-regulate the NF-kappaB signal upon being injected into a
      host cell via the T3SS. A recent report showed that NleE inhibits NF-kappaB
      activation, although an NleE-deficient pathogen was still immune-suppressive,
      indicating that other anti-inflammatory effectors are involved. In agreement, our
      present results showed that NleC was also required to inhibit inflammation. We
      found that NleC is a zinc protease that disrupts NF-kappaB activation by the
      direct cleavage of NF-kappaB's p65 subunit in the cytoplasm, thereby decreasing
      the available p65 and reducing the total nuclear entry of active p65. More
      importantly, we showed that a mutant EPEC/EHEC lacking both NleC and NleE
      (DeltanleC DeltanleE) caused greater inflammatory response than bacteria carrying
      DeltanleC or DeltanleE alone. This effect was similar to that of a T3SS-defective
      mutant. In conclusion, we found that NleC is an anti-inflammatory bacterial zinc
      protease, and that the cooperative function of NleE and NleC disrupts the NF
      kappaB pathway and accounts for most of the immune suppression caused by
      EHEC/EPEC.

PMID- 21187903
TI  - Mycobacterium tuberculosis eis regulates autophagy, inflammation, and cell death
      through redox-dependent signaling.
AB  - The "enhanced intracellular survival" (eis) gene of Mycobacterium tuberculosis
      (Mtb) is involved in the intracellular survival of M. smegmatis. However, its
      exact effects on host cell function remain elusive. We herein report that Mtb Eis
      plays essential roles in modulating macrophage autophagy, inflammatory responses,
      and cell death via a reactive oxygen species (ROS)-dependent pathway. Macrophages
      infected with an Mtb eis-deletion mutant H37Rv (Mtb-Deltaeis) displayed markedly
      increased accumulation of massive autophagic vacuoles and formation of
      autophagosomes in vitro and in vivo. Infection of macrophages with Mtb-Deltaeis
      increased the production of tumor necrosis factor-alpha and interleukin-6 over
      the levels produced by infection with wild-type or complemented strains. Elevated
      ROS generation in macrophages infected with Mtb-Deltaeis (for which NADPH oxidase
      and mitochondria were largely responsible) rendered the cells highly sensitive to
      autophagy activation and cytokine production. Despite considerable activation of
      autophagy and proinflammatory responses, macrophages infected with Mtb-Deltaeis
      underwent caspase-independent cell death. This cell death was significantly
      inhibited by blockade of autophagy and c-Jun N-terminal kinase-ROS signaling,
      suggesting that excessive autophagy and oxidative stress are detrimental to cell
      survival. Finally, artificial over-expression of Eis or pretreatment with
      recombinant Eis abrogated production of both ROS and proinflammatory cytokines,
      which depends on the N-acetyltransferase domain of the Eis protein. Collectively,
      these data indicate that Mtb Eis suppresses host innate immune defenses by
      modulating autophagy, inflammation, and cell death in a redox-dependent manner.

PMID- 21187905
TI  - Combining network modeling and gene expression microarray analysis to explore the
      dynamics of Th1 and Th2 cell regulation.
AB  - Two T helper (Th) cell subsets, namely Th1 and Th2 cells, play an important role
      in inflammatory diseases. The two subsets are thought to counter-regulate each
      other, and alterations in their balance result in different diseases. This
      paradigm has been challenged by recent clinical and experimental data. Because of
      the large number of genes involved in regulating Th1 and Th2 cells, assessment of
      this paradigm by modeling or experiments is difficult. Novel algorithms based on
      formal methods now permit the analysis of large gene regulatory networks. By
      combining these algorithms with in silico knockouts and gene expression
      microarray data from human T cells, we examined if the results were compatible
      with a counter-regulatory role of Th1 and Th2 cells. We constructed a directed
      network model of genes regulating Th1 and Th2 cells through text mining and
      manual curation. We identified four attractors in the network, three of which
      included genes that corresponded to Th0, Th1 and Th2 cells. The fourth attractor
      contained a mixture of Th1 and Th2 genes. We found that neither in silico
      knockouts of the Th1 and Th2 attractor genes nor gene expression microarray data
      from patients with immunological disorders and healthy subjects supported a
      counter-regulatory role of Th1 and Th2 cells. By combining network modeling with
      transcriptomic data analysis and in silico knockouts, we have devised a practical
      way to help unravel complex regulatory network topology and to increase our
      understanding of how network actions may differ in health and disease.

PMID- 21187906
TI  - Structural and functional studies of nonstructural protein 2 of the hepatitis C
      virus reveal its key role as organizer of virion assembly.
AB  - Non-structural protein 2 (NS2) plays an important role in hepatitis C virus (HCV)
      assembly, but neither the exact contribution of this protein to the assembly
      process nor its complete structure are known. In this study we used a combination
      of genetic, biochemical and structural methods to decipher the role of NS2 in
      infectious virus particle formation. A large panel of NS2 mutations targeting the
      N-terminal membrane binding region was generated. They were selected based on a
      membrane topology model that we established by determining the NMR structures of
      N-terminal NS2 transmembrane segments. Mutants affected in virion assembly, but
      not RNA replication, were selected for pseudoreversion in cell culture. Rescue
      mutations restoring virus assembly to various degrees emerged in E2, p7, NS3 and
      NS2 itself arguing for an interaction between these proteins. To confirm this
      assumption we developed a fully functional JFH1 genome expressing an N-terminally
      tagged NS2 demonstrating efficient pull-down of NS2 with p7, E2 and NS3 and, to a
      lower extent, NS5A. Several of the mutations blocking virus assembly disrupted
      some of these interactions that were restored to various degrees by those
      pseudoreversions that also restored assembly. Immunofluorescence analyses
      revealed a time-dependent NS2 colocalization with E2 at sites close to lipid
      droplets (LDs) together with NS3 and NS5A. Importantly, NS2 of a mutant defective
      in assembly abrogates NS2 colocalization around LDs with E2 and NS3, which is
      restored by a pseudoreversion in p7, whereas NS5A is recruited to LDs in an NS2
      independent manner. In conclusion, our results suggest that NS2 orchestrates HCV
      particle formation by participation in multiple protein-protein interactions
      required for their recruitment to assembly sites in close proximity of LDs.

PMID- 21187907
TI  - Rhythmic dynamics and synchronization via dimensionality reduction: application
      to human gait.
AB  - Reliable characterization of locomotor dynamics of human walking is vital to
      understanding the neuromuscular control of human locomotion and disease
      diagnosis. However, the inherent oscillation and ubiquity of noise in such non
      strictly periodic signals pose great challenges to current methodologies. To this
      end, we exploit the state-of-the-art technology in pattern recognition and,
      specifically, dimensionality reduction techniques, and propose to reconstruct and
      characterize the dynamics accurately on the cycle scale of the signal. This is
      achieved by deriving a low-dimensional representation of the cycles through
      global optimization, which effectively preserves the topology of the cycles that
      are embedded in a high-dimensional Euclidian space. Our approach demonstrates a
      clear advantage in capturing the intrinsic dynamics and probing the subtle
      synchronization patterns from uni/bivariate oscillatory signals over traditional
      methods. Application to human gait data for healthy subjects and diabetics
      reveals a significant difference in the dynamics of ankle movements and ankle
      knee coordination, but not in knee movements. These results indicate that the
      impaired sensory feedback from the feet due to diabetes does not influence the
      knee movement in general, and that normal human walking is not critically
      dependent on the feedback from the peripheral nervous system.

PMID- 21187908
TI  - The evolutionary analysis of emerging low frequency HIV-1 CXCR4 using variants
      through time--an ultra-deep approach.
AB  - Large-scale parallel pyrosequencing produces unprecedented quantities of sequence
      data. However, when generated from viral populations current mapping software is
      inadequate for dealing with the high levels of variation present, resulting in
      the potential for biased data loss. In order to apply the 454 Life Sciences'
      pyrosequencing system to the study of viral populations, we have developed
      software for the processing of highly variable sequence data. Here we demonstrate
      our software by analyzing two temporally sampled HIV-1 intra-patient datasets
      from a clinical study of maraviroc. This drug binds the CCR5 coreceptor, thus
      preventing HIV-1 infection of the cell. The objective is to determine viral
      tropism (CCR5 versus CXCR4 usage) and track the evolution of minority CXCR4-using
      variants that may limit the response to a maraviroc-containing treatment regimen.
      Five time points (two prior to treatment) were available from each patient. We
      first quantify the effects of divergence on initial read k-mer mapping and
      demonstrate the importance of utilizing population-specific template sequences in
      relation to the analysis of next-generation sequence data. Then, in conjunction
      with coreceptor prediction algorithms that infer HIV tropism, our software was
      used to quantify the viral population structure pre- and post-treatment. In both
      cases, low frequency CXCR4-using variants (2.5-15%) were detected prior to
      treatment. Following phylogenetic inference, these variants were observed to
      exist as distinct lineages that were maintained through time. Our analysis, thus
      confirms the role of pre-existing CXCR4-using virus in the emergence of maraviroc
      insensitive HIV. The software will have utility for the study of intra-host viral
      diversity and evolution of other fast evolving viruses, and is available from
      http://www.bioinf.manchester.ac.uk/segminator/.

PMID- 21187909
TI  - Mapping dynamic histone acetylation patterns to gene expression in nanog-depleted
      murine embryonic stem cells.
AB  - Embryonic stem cells (ESC) have the potential to self-renew indefinitely and to
      differentiate into any of the three germ layers. The molecular mechanisms for
      self-renewal, maintenance of pluripotency and lineage specification are poorly
      understood, but recent results point to a key role for epigenetic mechanisms. In
      this study, we focus on quantifying the impact of histone 3 acetylation
      (H3K9,14ac) on gene expression in murine embryonic stem cells. We analyze genome
      wide histone acetylation patterns and gene expression profiles measured over the
      first five days of cell differentiation triggered by silencing Nanog, a key
      transcription factor in ESC regulation. We explore the temporal and spatial
      dynamics of histone acetylation data and its correlation with gene expression
      using supervised and unsupervised statistical models. On a genome-wide scale,
      changes in acetylation are significantly correlated to changes in mRNA expression
      and, surprisingly, this coherence increases over time. We quantify the predictive
      power of histone acetylation for gene expression changes in a balanced cross
      validation procedure. In an in-depth study we focus on genes central to the
      regulatory network of Mouse ESC, including those identified in a recent genome
      wide RNAi screen and in the PluriNet, a computationally derived stem cell
      signature. We find that compared to the rest of the genome, ESC-specific genes
      show significantly more acetylation signal and a much stronger decrease in
      acetylation over time, which is often not reflected in a concordant expression
      change. These results shed light on the complexity of the relationship between
      histone acetylation and gene expression and are a step forward to dissect the
      multilayer regulatory mechanisms that determine stem cell fate.

PMID- 21187910
TI  - A single enhancer regulating the differential expression of duplicated red
      sensitive opsin genes in zebrafish.
AB  - A fundamental step in the evolution of the visual system is the gene duplication
      of visual opsins and differentiation between the duplicates in absorption spectra
      and expression pattern in the retina. However, our understanding of the mechanism
      of expression differentiation is far behind that of spectral tuning of opsins.
      Zebrafish (Danio rerio) have two red-sensitive cone opsin genes, LWS-1 and LWS-2.
      These genes are arrayed in a tail-to-head manner, in this order, and are both
      expressed in the long member of double cones (LDCs) in the retina. Expression of
      the longer-wave sensitive LWS-1 occurs later in development and is thus confined
      to the peripheral, especially ventral-nasal region of the adult retina, whereas
      expression of LWS-2 occurs earlier and is confined to the central region of the
      adult retina, shifted slightly to the dorsal-temporal region. In this study, we
      employed a transgenic reporter assay using fluorescent proteins and P1-artificial
      chromosome (PAC) clones encompassing the two genes and identified a 0.6-kb "LWS
      activating region" (LAR) upstream of LWS-1, which regulates expression of both
      genes. Under the 2.6-kb flanking upstream region containing the LAR, the
      expression pattern of LWS-1 was recapitulated by the fluorescent reporter. On the
      other hand, when LAR was directly conjugated to the LWS-2 upstream region, the
      reporter was expressed in the LDCs but also across the entire outer nuclear
      layer. Deletion of LAR from the PAC clones drastically lowered the reporter
      expression of the two genes. These results suggest that LAR regulates both LWS-1
      and LWS-2 by enhancing their expression and that interaction of LAR with the
      promoters is competitive between the two genes in a developmentally restricted
      manner. Sharing a regulatory region between duplicated genes could be a general
      way to facilitate the expression differentiation in duplicated visual opsins.

PMID- 21187911
TI  - Mathematical model of a cell size checkpoint.
AB  - How cells regulate their size from one generation to the next has remained an
      enigma for decades. Recently, a molecular mechanism that links cell size and cell
      cycle was proposed in fission yeast. This mechanism involves changes in the
      spatial cellular distribution of two proteins, Pom1 and Cdr2, as the cell grows.
      Pom1 inhibits Cdr2 while Cdr2 promotes the G2 -> M transition. Cdr2 is localized
      in the middle cell region (midcell) whereas the concentration of Pom1 is highest
      at the cell tips and declines towards the midcell. In short cells, Pom1
      efficiently inhibits Cdr2. However, as cells grow, the Pom1 concentration at
      midcell decreases such that Cdr2 becomes activated at some critical size. In this
      study, the chemistry of Pom1 and Cdr2 was modeled using a deterministic reaction
      diffusion-convection system interacting with a deterministic model describing
      microtubule dynamics. Simulations mimicked experimental data from wild-type (WT)
      fission yeast growing at normal and reduced rates; they also mimicked the
      behavior of a Pom1 overexpression mutant and WT yeast exposed to a microtubule
      depolymerizing drug. A mechanism linking cell size and cell cycle, involving the
      downstream action of Cdr2 on Wee1 phosphorylation, is proposed.

PMID- 21187912
TI  - The killing of African trypanosomes by ethidium bromide.
AB  - Introduced in the 1950s, ethidium bromide (EB) is still used as an anti
      trypanosomal drug for African cattle although its mechanism of killing has been
      unclear and controversial. EB has long been known to cause loss of the
      mitochondrial genome, named kinetoplast DNA (kDNA), a giant network of
      interlocked minicircles and maxicircles. However, the existence of viable
      parasites lacking kDNA (dyskinetoplastic) led many to think that kDNA loss could
      not be the mechanism of killing. When recent studies indicated that kDNA is
      indeed essential in bloodstream trypanosomes and that dyskinetoplastic cells
      survive only if they have a compensating mutation in the nuclear genome, we
      investigated the effect of EB on kDNA and its replication. We here report some
      remarkable effects of EB. Using EM and other techniques, we found that binding of
      EB to network minicircles is low, probably because of their association with
      proteins that prevent helix unwinding. In contrast, covalently-closed minicircles
      that had been released from the network for replication bind EB extensively,
      causing them, after isolation, to become highly supertwisted and to develop
      regions of left-handed Z-DNA (without EB, these circles are fully relaxed). In
      vivo, EB causes helix distortion of free minicircles, preventing replication
      initiation and resulting in kDNA loss and cell death. Unexpectedly, EB also kills
      dyskinetoplastic trypanosomes, lacking kDNA, by inhibiting nuclear replication.
      Since the effect on kDNA occurs at a >10-fold lower EB concentration than that on
      nuclear DNA, we conclude that minicircle replication initiation is likely EB's
      most vulnerable target, but the effect on nuclear replication may also contribute
      to cell killing.

PMID- 21187913
TI  - Blockade of immunosuppressive cytokines restores NK cell antiviral function in
      chronic hepatitis B virus infection.
AB  - NK cells are enriched in the liver, constituting around a third of intrahepatic
      lymphocytes. We have previously demonstrated that they upregulate the death
      ligand TRAIL in patients with chronic hepatitis B virus infection (CHB), allowing
      them to kill hepatocytes bearing TRAIL receptors. In this study we investigated
      whether, in addition to their pathogenic role, NK cells have antiviral potential
      in CHB. We characterised NK cell subsets and effector function in 64 patients
      with CHB compared to 31 healthy controls. We found that, in contrast to their
      upregulated TRAIL expression and maintenance of cytolytic function, NK cells had
      a markedly impaired capacity to produce IFN-gamma in CHB. This functional
      dichotomy of NK cells could be recapitulated in vitro by exposure to the
      immunosuppressive cytokine IL-10, which was induced in patients with active CHB.
      IL-10 selectively suppressed NK cell IFN-gamma production without altering
      cytotoxicity or death ligand expression. Potent antiviral therapy reduced TRAIL
      expressing CD56(bright) NK cells, consistent with the reduction in liver
      inflammation it induced; however, it was not able to normalise IL-10 levels or
      the capacity of NK cells to produce the antiviral cytokine IFN-gamma. Blockade of
      IL-10 +/- TGF-beta restored the capacity of NK cells from both the periphery and
      liver of patients with CHB to produce IFN-gamma, thereby enhancing their non
      cytolytic antiviral capacity. In conclusion, NK cells may be driven to a state of
      partial functional tolerance by the immunosuppressive cytokine environment in
      CHB. Their defective capacity to produce the antiviral cytokine IFN-gamma
      persists in patients on antiviral therapy but can be corrected in vitro by IL
      10+/- TGF-beta blockade.

PMID- 21187914
TI  - Obesity impact on the attentional cost for controlling posture.
AB  - BACKGROUND: This study investigated the effects of obesity on attentional
      resources allocated to postural control in seating and unipedal standing.
      METHODS: Ten non obese adults (BMI = 22.4+/-1.3, age = 42.4+/-15.1) and 10 obese
      adult patients (BMI = 35.2+/-2.8, age = 46.2+/-19.6) maintained postural
      stability on a force platform in two postural tasks (seated and unipedal). The
      two postural tasks were performed (1) alone and (2) in a dual-task paradigm in
      combination with an auditory reaction time task (RT). Performing the RT task
      together with the postural one was supposed to require some attentional resources
      that allowed estimating the attentional cost of postural control. 4 trials were
      performed in each condition for a total of 16 trials. FINDINGS: (1) Whereas
      seated non obese and obese patients exhibited similar centre of foot pressure
      oscillations (CoP), in the unipedal stance only obese patients strongly increased
      their CoP sway in comparison to controls. (2) Whatever the postural task, the
      additional RT task did not affect postural stability. (3) Seated, RT did not
      differ between the two groups. (4) RT strongly increased between the two postural
      conditions in the obese patients only, suggesting that body schema and the use of
      internal models was altered with obesity. INTERPRETATION: Obese patients needed
      more attentional resources to control postural stability during unipedal stance
      than non obese participants. This was not the case in a more simple posture such
      as seating. To reduce the risk of fall as indicated by the critical values of CoP
      displacement, obese patients must dedicate a strong large part of their
      attentional resources to postural control, to the detriment of non-postural
      events. Obese patients were not able to easily perform multitasking as healthy
      adults do, reflecting weakened psycho-motor abilities.

PMID- 21187915
TI  - Specificity of the E. coli LysR-type transcriptional regulators.
AB  - BACKGROUND: Families of paralogous oligomeric proteins are common in biology. How
      the specificity of assembly evolves is a fundamental question of biology. The
      LysR-Type Transcriptional Regulators (LTTR) form perhaps the largest family of
      transcriptional regulators in bacteria. Because genomes often encode many LTTR
      family members, it is assumed that many distinct homooligomers are formed
      simultaneously in the same cell without interfering with each other's activities,
      suggesting specificity in the interactions. However, this assumption has not been
      systematically tested. METHODOLOGY/PRINCIPAL FINDINGS: A negative-dominant assay
      with lambdacI repressor fusions was used to evaluate the assembly of the LTTRs in
      E. coli K-12. Thioredoxin (Trx)-LTTR fusions were used to challenge the
      homooligomeric interactions of lambdacI-LTTR fusions. Eight cI-LTTR fusions were
      challenged with twenty-eight Trx fusions. LTTRs could be divided into three
      classes based on their interactions with other LTTRs. CONCLUSIONS/SIGNIFICANCE:
      Multimerization of LTTRs in E. coli K-12 is mostly specific. However, under the
      conditions of the assay, many LTTRs interact with more than one noncognate
      partner. The physiological significance and physical basis for these interactions
      are not known.

PMID- 21187916
TI  - Genome-wide analysis of glucocorticoid receptor binding regions in adipocytes
      reveal gene network involved in triglyceride homeostasis.
AB  - Glucocorticoids play important roles in the regulation of distinct aspects of
      adipocyte biology. Excess glucocorticoids in adipocytes are associated with
      metabolic disorders, including central obesity, insulin resistance and
      dyslipidemia. To understand the mechanisms underlying the glucocorticoid action
      in adipocytes, we used chromatin immunoprecipitation sequencing to isolate genome
      wide glucocorticoid receptor (GR) binding regions (GBRs) in 3T3-L1 adipocytes.
      Furthermore, gene expression analyses were used to identify genes that were
      regulated by glucocorticoids. Overall, 274 glucocorticoid-regulated genes contain
      or locate nearby GBR. We found that many GBRs were located in or nearby genes
      involved in triglyceride (TG) synthesis (Scd-1, 2, 3, GPAT3, GPAT4, Agpat2,
      Lpin1), lipolysis (Lipe, Mgll), lipid transport (Cd36, Lrp-1, Vldlr, Slc27a2) and
      storage (S3-12). Gene expression analysis showed that except for Scd-3, the other
      13 genes were induced in mouse inguinal fat upon 4-day glucocorticoid treatment.
      Reporter gene assays showed that except Agpat2, the other 12 glucocorticoid
      regulated genes contain at least one GBR that can mediate hormone response. In
      agreement with the fact that glucocorticoids activated genes in both TG
      biosynthetic and lipolytic pathways, we confirmed that 4-day glucocorticoid
      treatment increased TG synthesis and lipolysis concomitantly in inguinal fat.
      Notably, we found that 9 of these 12 genes were induced in transgenic mice that
      have constant elevated plasma glucocorticoid levels. These results suggested that
      a similar mechanism was used to regulate TG homeostasis during chronic
      glucocorticoid treatment. In summary, our studies have identified molecular
      components in a glucocorticoid-controlled gene network involved in the regulation
      of TG homeostasis in adipocytes. Understanding the regulation of this gene
      network should provide important insight for future therapeutic developments for
      metabolic diseases.

PMID- 21187917
TI  - Concentration-dependent toxicity of iron oxide nanoparticles mediated by
      increased oxidative stress.
AB  - Iron oxide nanoparticles with unique magnetic properties have a high potential
      for use in several biomedical, bioengineering and in vivo applications, including
      tissue repair, magnetic resonance imaging, immunoassay, drug delivery,
      detoxification of biologic fluids, cell sorting, and hyperthermia. Although
      various surface modifications are being done for making these nonbiodegradable
      nanoparticles more biocompatible, their toxic potential is still a major concern.
      The current in vitro study of the interaction of superparamagnetic iron oxide
      nanoparticles of mean diameter 30 nm coated with Tween 80 and murine macrophage
      (J774) cells was undertaken to evaluate the dose- and time-dependent toxic
      potential, as well as investigate the role of oxidative stress in the toxicity. A
      15-30 nm size range of spherical nanoparticles were characterized by transmission
      electron microscopy and zeta sizer. MTT assay showed >95% viability of cells in
      lower concentrations (25-200 MUg/mL) and up to three hours of exposure, whereas
      at higher concentrations (300-500 MUg/mL) and prolonged (six hours) exposure
      viability reduced to 55%-65%. Necrosis-apoptosis assay by propidium iodide and
      Hoechst-33342 staining revealed loss of the majority of the cells by apoptosis.
      H2DCFDDA assay to quantify generation of intracellular reactive oxygen species
      (ROS) indicated that exposure to a higher concentration of nanoparticles resulted
      in enhanced ROS generation, leading to cell injury and death. The cell membrane
      injury induced by nanoparticles studied using the lactate dehydrogenase assay,
      showed both concentration- and time-dependent damage. Thus, this study concluded
      that use of a low optimum concentration of superparamagnetic iron oxide
      nanoparticles is important for avoidance of oxidative stress-induced cell injury
      and death.

PMID- 21187918
TI  - Non-invasive and transdermal measurement of blood uric acid level in human by
      electroporation and reverse iontophoresis.
AB  - The aim of this study was to find out the optimum combination of electroporation
      (EP) and reverse iontophoresis (RI) on noninvasive and transdermal determination
      of blood uric acid level in humans. EP is the use of high-voltage electric pulse
      to create nano-channels on the stratum corneum, temporarily and reversibly. RI is
      the use of small current to facilitate both charged and uncharged molecule
      transportation across the skin. It is believed that the combination of these two
      techniques has additional benefits on the molecules' extraction across the human
      skin. In vitro studies using porcine skin and diffusion cell have indicated that
      the optimum mode for transdermal uric acid extraction is the combination of RI
      with symmetrical biphasic direct current (current density = 0.3 mA/cm2; phase
      duration = 180 s) and EP with 10 pulses per second (voltage = 100 V/cm2; pulse
      width = 1 ms). This optimum mode was applied to six human subjects. Uric acid was
      successfully extracted through the subjects' skin into the collection solution. A
      good correlation (r2 = 0.88) between the subject's blood uric acid level and uric
      acid concentrations in collection solutions was observed. The results suggest
      that it may be possible to noninvasively and transdermally determine blood uric
      acid levels.

PMID- 21187919
TI  - Magnetic Fe3O4 nanoparticles and chemotherapy agents interact synergistically to
      induce apoptosis in lymphoma cells.
AB  - The purpose of this study was to investigate the potential effects of combination
      therapy using magnetic nanoparticles of Fe3O4 (MNP-Fe3O4) and chemotherapeutic
      drugs on lymphoma cells. Proliferation, inhibition, and viability of Raji cells
      were detected by MTT and trypan blue exclusion. The percentage of cells
      undergoing apoptosis was detected by flow cytometry using fluorescein
      isothiocyanate-annexin V and propidium iodide staining. p53 and nuclear factor
      kappaB (NF-kappaB) protein levels were measured by Western blot. The results
      showed that proliferation of Raji cells was inhibited by adriamycin or
      daunorubicin in a dose-and time-dependent manner. Cell sensitivity was improved
      and the 50% inhibitory concentrations of adriamycin and daunorubicin decreased
      when combined with a MNP-Fe3O4 carrier. Interestingly, increased apoptosis in
      Raji lymphoma cells was accompanied by upregulation of p53 protein and
      downregulation of NF-kappaB protein. Furthermore, the combination of MNP-Fe3O4
      with adriamycin or daunorubicin increased p53 protein levels and decreased NF
      kappaB protein levels more than adriamycin or daunorubicin alone, indicating that
      MNP-Fe3O4 could enhance the effect of chemotherapeutic drugs on p53 and NF
      kappaB. Similar results for cell apoptosis and protein expression were not
      observed for the groups treated with dexamethasone +/- MNP-Fe3O4 (P > 0.05).
      These findings suggest a potential clinical application for MNP-Fe3O4 in
      combination with daunorubicin or adriamycin in the treatment of lymphoma.

PMID- 21187920
TI  - Viral epidemics in a cell culture: novel high resolution data and their
      interpretation by a percolation theory based model.
AB  - Because of its relevance to everyday life, the spreading of viral infections has
      been of central interest in a variety of scientific communities involved in
      fighting, preventing and theoretically interpreting epidemic processes. Recent
      large scale observations have resulted in major discoveries concerning the
      overall features of the spreading process in systems with highly mobile
      susceptible units, but virtually no data are available about observations of
      infection spreading for a very large number of immobile units. Here we present
      the first detailed quantitative documentation of percolation-type viral epidemics
      in a highly reproducible in vitro system consisting of tens of thousands of
      virtually motionless cells. We use a confluent astroglial monolayer in a Petri
      dish and induce productive infection in a limited number of cells with a
      genetically modified herpesvirus strain. This approach allows extreme high
      resolution tracking of the spatio-temporal development of the epidemic. We show
      that a simple model is capable of reproducing the basic features of our
      observations, i.e., the observed behaviour is likely to be applicable to many
      different kinds of systems. Statistical physics inspired approaches to our data,
      such as fractal dimension of the infected clusters as well as their size
      distribution, seem to fit into a percolation theory based interpretation. We
      suggest that our observations may be used to model epidemics in more complex
      systems, which are difficult to study in isolation.

PMID- 21187921
TI  - Genetic variation in the complete MgPa operon and its repetitive chromosomal
      elements in clinical strains of Mycoplasma genitalium.
AB  - Mycoplasma genitalium has been increasingly recognized as an important microbe
      not only because of its significant association with human genital tract diseases
      but also because of its utility as a model for studying the minimum set of genes
      necessary to sustain life. Despite its small genome, 4.7% of the total genome
      sequence is devoted to making the MgPa adhesin operon and its nine chromosomal
      repetitive elements (termed MgPars). The MgPa operon, along with 9 MgPars, is
      believed to play an important role in pathogenesis of M. genitalium infection and
      has also served as the main target for development of diagnostic tools. However,
      genetic variation in the complete MgPa operon and MgPars among clinical strains
      of M. genitalium has not been addressed. In this study we examined the genetic
      variation in the complete MgPa operon (approximately 8.5 kb) and full or partial
      MgPar sequences (0.4-2.6 kb) in 15 geographically diverse strains of M.
      genitalium. Extensive variation was present in four repeat regions of the MgPa
      operon (with homology to MgPars) among and within strains while the non-repeat
      regions (without homology to MgPars) showed low-level variation among strains and
      no variation within strains. MgPars showed significant variation among strains
      but were highly homogeneous within strains, supporting gene conversion as the
      likely recombination mechanism. When applying our sequence data to evaluate
      published MgPa operon-based diagnostic PCR assays and genotyping systems, we
      found that 11 of 19 primers contain up to 19 variable nucleotides and that the
      target for one of two typing systems is located in a hypervariable repeat region,
      suggesting the likelihood of false results with some of these assays. This study
      not only provides new insights into the role of the MgPa operon in the
      pathogenesis of M. genitalium infection but has important implications for the
      development of diagnostic tools.

PMID- 21187922
TI  - Tailoring adjuvant endocrine therapy for postmenopausal breast cancer: a CYP2D6
      multiple-genotype-based modeling analysis and validation.
AB  - PURPOSE: Previous studies have suggested that postmenopausal women with breast
      cancer who present with wild-type CYP2D6 may actually have similar or superior
      recurrence-free survival outcomes when given tamoxifen in place of aromatase
      inhibitors (AIs). The present study established a CYP2D6 multiple-genotype-based
      model to determine the optimal endocrine therapy for patients harboring wild-type
      CYP2D6. METHODS: We created a Markov model to determine whether tamoxifen or AIs
      maximized 5-year disease-free survival (DFS) for extensive metabolizer (EM)
      patients using annual hazard ratio (HR) data from the BIG 1-98 trial. We then
      replicated the model by evaluating 9-year event-free survival (EFS) using HR data
      from the ATAC trial. In addition, we employed two-way sensitivity analyses to
      explore the impact of HR of decreased-metabolizer (DM) and its frequency on
      survival by studying a range of estimates. RESULTS: The 5-year DFS of tamoxifen
      treated EM patients was 83.3%, which is similar to that of genotypically
      unselected patients who received an AI (83.7%). In the validation study, we
      further demonstrated that the 9-year EFS of tamoxifen-treated EM patients was
      81.4%, which is higher than that of genotypically unselected patients receiving
      tamoxifen (78.4%) and similar to that of patients receiving an AI (83.2%). Two
      way sensitivity analyses demonstrated the robustness of the results. CONCLUSIONS:
      Our modeling analyses indicate that, among EM patients, the DFS/EFS outcome of
      patients receiving tamoxifen is similar to that of patients receiving an AI.
      Further prospective clinical trials are needed to evaluate the value of the
      CYP2D6 genotype in the selection of endocrine therapy.

PMID- 21187923
TI  - KIFC1-like motor protein associates with the cephalopod manchette and
      participates in sperm nuclear morphogenesis in Octopus tankahkeei.
AB  - BACKGROUND: Nuclear morphogenesis is one of the most fundamental cellular
      transformations taking place during spermatogenesis. In rodents, a microtubule
      based perinuclear structure, the manchette, and a C-terminal kinesin motor KIFC1
      are believed to play crucial roles in this process. Spermatogenesis in Octopus
      tankahkeei is a good model system to explore whether evolution has created a
      cephalopod prototype of mammalian manchette-based and KIFC1-dependent sperm
      nuclear shaping machinery. METHODOLOGY/PRINCIPAL FINDINGS: We detected the
      presence of a KIFC1-like protein in the testis, muscle, and liver of O.
      tankahkeei by Western Blot. Then we tracked its dynamic localization in spermatic
      cells at various stages using Immunofluorescence and Immunogold Electron
      Microscopy. The KIFC1-like protein was not expressed at early stages of
      spermatogenesis when no significant morphological changes occur, began to be
      present in early spermatid, localized around and in the nucleus of intermediate
      and late spermatids where the nucleus was dramatically elongated and compressed,
      and concentrated at one end of final spermatid. Furthermore, distribution of the
      motor protein during nuclear elongation and condensation overlapped with that of
      the cephalopod counterpart of manchette at a significant level.
      CONCLUSIONS/SIGNIFICANCE: The results support the assumption that the protein is
      actively involved in sperm nuclear morphogenesis in O. tankahkeei possibly
      through bridging the manchette-like perinuclear microtubules to the nucleus and
      assisting in the nucleocytoplasmic trafficking of specific cargoes. This study
      represents the first description of the role of a motor protein in sperm nuclear
      shaping in cephalopod.

PMID- 21187924
TI  - Non-invasive in vivo imaging of tumor-associated CD133/prominin.
AB  - BACKGROUND: Cancer stem cells are thought to play a pivotal role in tumor
      maintenance, metastasis, tumor therapy resistance and relapse. Hence, the
      development of methods for non-invasive in vivo detection of cancer stem cells is
      of great importance. METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe successful
      in vivo detection of CD133/prominin, a cancer stem cell surface marker for a
      variety of tumor entities. The CD133-specific monoclonal antibody AC133.1 was
      used for quantitative fluorescence-based optical imaging of mouse xenograft
      models based on isogenic pairs of CD133 positive and negative cell lines. A first
      set consisted of wild-type U251 glioblastoma cells, which do not express CD133,
      and lentivirally transduced CD133-overexpressing U251 cells. A second set made
      use of HCT116 colon carcinoma cells, which uniformly express CD133 at levels
      comparable to primary glioblastoma stem cells, and a CD133-negative HCT116
      derivative. Not surprisingly, visualization and quantification of CD133 in
      overexpressing U251 xenografts was successful; more importantly, however,
      significant differences were also found in matched HCT116 xenograft pairs,
      despite the lower CD133 expression levels. The binding of i.v.-injected AC133.1
      antibodies to CD133 positive, but not negative, tumor cells isolated from
      xenografts was confirmed by flow cytometry. CONCLUSIONS/SIGNIFICANCE: Taken
      together, our results show that non-invasive antibody-based in vivo imaging of
      tumor-associated CD133 is feasible and that CD133 antibody-based tumor targeting
      is efficient. This should facilitate developing clinically applicable cancer stem
      cell imaging methods and CD133 antibody-based therapeutics.

PMID- 21187925
TI  - p38 MAPK and JNK antagonistically control senescence and cytoplasmic p16INK4A
      expression in doxorubicin-treated endothelial progenitor cells.
AB  - Patients treated with low-dose anthracyclines often show late onset
      cardiotoxicity. Recent studies suggest that this form of cardiotoxicity is the
      result of a progenitor cell disease. In this study we demonstrate that Cord Blood
      Endothelial Progenitor Cells (EPCs) exposed to low, sub-apoptotic doses of
      doxorubicin show a senescence phenotype characterized by increased SA-b-gal
      activity, decreased TRF2 and chromosomal abnormalities, enlarged cell shape, and
      disarrangement of F-actin stress fibers accompanied by impaired migratory
      ability. P16( INK4A) localizes in the cytoplasm of doxorubicin-induced senescent
      EPCs and not in the nucleus as is the case in EPCs rendered senescent by
      different stimuli. This localization together with the presence of an arrest in
      G2, and not at the G1 phase boundary, which is what usually occurs in response to
      the cell cycle regulatory activity of p16(INK4A), suggests that doxorubicin
      induced p16( INK4A) does not regulate the cell cycle, even though its increase is
      closely associated with senescence. The effects of doxorubicin are the result of
      the activation of MAPKs p38 and JNK which act antagonistically. JNK attenuates
      the senescence, p16( INK4A) expression and cytoskeleton remodeling that are
      induced by activated p38. We also found that conditioned medium from doxorubicin
      induced senescent cardiomyocytes does not attract untreated EPCs, unlike
      conditioned medium from apoptotic cardiomyocytes which has a strong
      chemoattractant capacity. In conclusion, this study provides a better
      understanding of the senescence of doxorubicin-treated EPCs, which may be helpful
      in preventing and treating late onset cardiotoxicity.

PMID- 21187926
TI  - Macroautophagy-mediated degradation of whole nuclei in the filamentous fungus
      Aspergillus oryzae.
AB  - Filamentous fungi consist of continuum of multinucleate cells called hyphae, and
      proliferate by means of hyphal tip growth. Accordingly, research interest has
      been focusing on hyphal tip cells, but little is known about basal cells in
      colony interior that do not directly contribute to proliferation. Here, we show
      that autophagy mediates degradation of basal cell components in the filamentous
      fungus Aspergillus oryzae. In basal cells, enhanced green fluorescent protein
      (EGFP)-labeled peroxisomes, mitochondria, and even nuclei were taken up into
      vacuoles in an autophagy-dependent manner. During this process, crescents of
      autophagosome precursors matured into ring-like autophagosomes to encircle
      apparently whole nuclei. The ring-like autophagosomes then disappeared, followed
      by dispersal of the nuclear material throughout the vacuoles, suggesting the
      autophagy-mediated degradation of whole nuclei. We also demonstrated that colony
      growth in a nutrient-depleted medium was significantly inhibited in the absence
      of functional autophagy. This is a first report describing autophagy-mediated
      degradation of whole nuclei, as well as suggesting a novel strategy of
      filamentous fungi to degrade components of existing hyphae for use as nutrients
      to support mycelial growth in order to counteract starvation.

PMID- 21187927
TI  - Heart rate during conflicts predicts post-conflict stress-related behavior in
      greylag geese.
AB  - BACKGROUND: Social stressors are known to be among the most potent stressors in
      group-living animals. This is not only manifested in individual physiology (heart
      rate, glucocorticoids), but also in how individuals behave directly after a
      conflict. Certain 'stress-related behaviors' such as autopreening, body shaking,
      scratching and vigilance have been suggested to indicate an individual's
      emotional state. Such behaviors may also alleviate stress, but the behavioral
      context and physiological basis of those behaviors is still poorly understood.
      METHODOLOGY/PRINCIPAL FINDINGS: We recorded beat-to-beat heart rates (HR) of 22
      greylag geese in response to agonistic encounters using fully implanted sensor
      transmitter packages. Additionally, for 143 major events we analyzed the behavior
      shown by our focal animals in the first two minutes after an interaction. Our
      results show that the HR during encounters and characteristics of the interaction
      predicted the frequency and duration of behaviors shown after a conflict.
      CONCLUSIONS/SIGNIFICANCE: To our knowledge this is the first study to quantify
      the physiological and behavioral responses to single agonistic encounters and to
      link this to post conflict behavior. Our results demonstrate that 'stress-related
      behaviors' are flexibly modulated by the characteristics of the preceding
      aggressive interaction and reflect the individual's emotional strain, which is
      linked to autonomic arousal. We found no support for the stress-alleviating
      hypothesis, but we propose that stress-related behaviors may play a role in
      communication with other group members, particularly with pair-partners.

PMID- 21187928
TI  - Gene expression of axon growth promoting factors in the deer antler.
AB  - The annual regeneration cycle of deer (Cervidae, Artiodactyla) antlers represents
      a unique model of epimorphic regeneration and rapid growth in adult mammals.
      Regenerating antlers are innervated by trigeminal sensory axons growing through
      the velvet, the modified form of skin that envelopes the antler, at elongation
      velocities that reach one centimetre per day in the common deer (Cervus elaphus).
      Several axon growth promoters like NT-3, NGF or IGF-1 have been described in the
      antler. To increase the knowledge on the axon growth environment, we have
      combined different gene-expression techniques to identify and characterize the
      expression of promoting molecules not previously described in the antler velvet.
      Cross-species microarray analyses of deer samples on human arrays allowed us to
      build up a list of 90 extracellular or membrane molecules involved in axon growth
      that were potentially being expressed in the antler. Fifteen of these genes were
      analysed using PCR and sequencing techniques to confirm their expression in the
      velvet and to compare it with the expression in other antler and skin samples.
      Expression of 8 axon growth promoters was confirmed in the velvet, 5 of them not
      previously described in the antler. In conclusion, our work shows that antler
      velvet provides growing axons with a variety of promoters of axon growth, sharing
      many of them with deer's normal and pedicle skin.

PMID- 21187929
TI  - Sequence homology at the breakpoint and clinical phenotype of mitochondrial DNA
      deletion syndromes.
AB  - Mitochondrial DNA (mtDNA) deletions are a common cause of mitochondrial
      disorders. Large mtDNA deletions can lead to a broad spectrum of clinical
      features with different age of onset, ranging from mild mitochondrial myopathies
      (MM), progressive external ophthalmoplegia (PEO), and Kearns-Sayre syndrome
      (KSS), to severe Pearson syndrome. The aim of this study is to investigate the
      molecular signatures surrounding the deletion breakpoints and their association
      with the clinical phenotype and age at onset. MtDNA deletions in 67 patients were
      characterized using array comparative genomic hybridization (aCGH) followed by
      PCR-sequencing of the deletion junctions. Sequence homology including both
      perfect and imperfect short repeats flanking the deletion regions were analyzed
      and correlated with clinical features and patients' age group. In all age groups,
      there was a significant increase in sequence homology flanking the deletion
      compared to mtDNA background. The youngest patient group (<6 years old) showed a
      diffused pattern of deletion distribution in size and locations, with a
      significantly lower sequence homology flanking the deletion, and the highest
      percentage of deletion mutant heteroplasmy. The older age groups showed rather
      discrete pattern of deletions with 44% of all patients over 6 years old carrying
      the most common 5 kb mtDNA deletion, which was found mostly in muscle specimens
      (22/41). Only 15% (3/20) of the young patients (<6 years old) carry the 5 kb
      common deletion, which is usually present in blood rather than muscle. This group
      of patients predominantly (16 out of 17) exhibit multisystem disorder and/or
      Pearson syndrome, while older patients had predominantly neuromuscular
      manifestations including KSS, PEO, and MM. In conclusion, sequence homology at
      the deletion flanking regions is a consistent feature of mtDNA deletions.
      Decreased levels of sequence homology and increased levels of deletion mutant
      heteroplasmy appear to correlate with earlier onset and more severe disease with
      multisystem involvement.

PMID- 21187930
TI  - Multiplexed echo planar imaging for sub-second whole brain FMRI and fast
      diffusion imaging.
AB  - Echo planar imaging (EPI) is an MRI technique of particular value to
      neuroscience, with its use for virtually all functional MRI (fMRI) and diffusion
      imaging of fiber connections in the human brain. EPI generates a single 2D image
      in a fraction of a second; however, it requires 2-3 seconds to acquire multi
      slice whole brain coverage for fMRI and even longer for diffusion imaging. Here
      we report on a large reduction in EPI whole brain scan time at 3 and 7 Tesla,
      without significantly sacrificing spatial resolution, and while gaining
      functional sensitivity. The multiplexed-EPI (M-EPI) pulse sequence combines two
      forms of multiplexing: temporal multiplexing (m) utilizing simultaneous echo
      refocused (SIR) EPI and spatial multiplexing (n) with multibanded RF pulses (MB)
      to achieve m*n images in an EPI echo train instead of the normal single image.
      This resulted in an unprecedented reduction in EPI scan time for whole brain fMRI
      performed at 3 Tesla, permitting TRs of 400 ms and 800 ms compared to a more
      conventional 2.5 sec TR, and 2-4 times reductions in scan time for HARDI imaging
      of neuronal fibertracks. The simultaneous SE refocusing of SIR imaging at 7 Tesla
      advantageously reduced SAR by using fewer RF refocusing pulses and by shifting
      fat signal out of the image plane so that fat suppression pulses were not
      required. In preliminary studies of resting state functional networks identified
      through independent component analysis, the 6-fold higher sampling rate increased
      the peak functional sensitivity by 60%. The novel M-EPI pulse sequence resulted
      in a significantly increased temporal resolution for whole brain fMRI, and as
      such, this new methodology can be used for studying non-stationarity in networks
      and generally for expanding and enriching the functional information.

PMID- 21187931
TI  - Prophage spontaneous activation promotes DNA release enhancing biofilm formation
      in Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae (pneumococcus) is able to form biofilms in vivo and
      previous studies propose that pneumococcal biofilms play a relevant role both in
      colonization and infection. Additionally, pneumococci recovered from human
      infections are characterized by a high prevalence of lysogenic bacteriophages
      (phages) residing quiescently in their host chromosome. We investigated a
      possible link between lysogeny and biofilm formation. Considering that
      extracellular DNA (eDNA) is a key factor in the biofilm matrix, we reasoned that
      prophage spontaneous activation with the consequent bacterial host lysis could
      provide a source of eDNA, enhancing pneumococcal biofilm development. Monitoring
      biofilm growth of lysogenic and non-lysogenic pneumococcal strains indicated that
      phage-infected bacteria are more proficient at forming biofilms, that is their
      biofilms are characterized by a higher biomass and cell viability. The presence
      of phage particles throughout the lysogenic strains biofilm development
      implicated prophage spontaneous induction in this effect. Analysis of lysogens
      deficient for phage lysin and the bacterial major autolysin revealed that the
      absence of either lytic activity impaired biofilm development and the addition of
      DNA restored the ability of mutant strains to form robust biofilms. These
      findings establish that limited phage-mediated host lysis of a fraction of the
      bacterial population, due to spontaneous phage induction, constitutes an
      important source of eDNA for the S. pneumoniae biofilm matrix and that this
      localized release of eDNA favors biofilm formation by the remaining bacterial
      population.

PMID- 21187932
TI  - A mitosis block links active cell cycle with human epidermal differentiation and
      results in endoreplication.
AB  - How human self-renewal tissues co-ordinate proliferation with differentiation is
      unclear. Human epidermis undergoes continuous cell growth and differentiation and
      is permanently exposed to mutagenic hazard. Keratinocytes are thought to arrest
      cell growth and cell cycle prior to terminal differentiation. However, a growing
      body of evidence does not satisfy this model. For instance, it does not explain
      how skin maintains tissue structure in hyperproliferative benign lesions. We have
      developed and applied novel cell cycle techniques to human skin in situ and
      determined the dynamics of key cell cycle regulators of DNA replication or
      mitosis, such as cyclins E, A and B, or members of the anaphase promoting complex
      pathway: cdc14A, Ndc80/Hec1 and Aurora kinase B. The results show that actively
      cycling keratinocytes initiate terminal differentiation, arrest in mitosis,
      continue DNA replication in a special G2/M state, and become polyploid by mitotic
      slippage. They unambiguously demonstrate that cell cycle progression coexists
      with terminal differentiation, thus explaining how differentiating cells increase
      in size. Epidermal differentiating cells arrest in mitosis and a genotoxic
      induced mitosis block rapidly pushes epidermal basal cells into differentiation
      and polyploidy. These observations unravel a novel mitosis-differentiation link
      that provides new insight into skin homeostasis and cancer. It might constitute a
      self-defence mechanism against oncogenic alterations such as Myc deregulation.

PMID- 21187933
TI  - Isolation of proteinase K-sensitive prions using pronase E and phosphotungstic
      acid.
AB  - Disease-related prion protein, PrP(Sc), is classically distinguished from its
      normal cellular precursor, PrP(C), by its detergent insolubility and partial
      resistance to proteolysis. Molecular diagnosis of prion disease typically relies
      upon detection of protease-resistant fragments of PrP(Sc) using proteinase K,
      however it is now apparent that the majority of disease-related PrP and indeed
      prion infectivity may be destroyed by this treatment. Here we report that
      digestion of RML prion-infected mouse brain with pronase E, followed by
      precipitation with sodium phosphotungstic acid, eliminates the large majority of
      brain proteins, including PrP(C), while preserving >70% of infectious prion
      titre. This procedure now allows characterization of proteinase K-sensitive
      prions and investigation of their clinical relevance in human and animal prion
      disease without being confounded by contaminating PrP(C).

PMID- 21187934
TI  - Identification of protozoa in dairy lagoon wastewater that consume Escherichia
      coli O157:H7 preferentially.
AB  - Escherichia coli O157:H7 (EcO157), an agent of life threatening hemolytic-uremic
      syndrome, resides in ruminants and is released in feces at numbers as high as 10
      million cells/gram. EcO157 could survive in manure for as long as 21 months, but
      we observed a 90% decrease in cells of an outbreak strain of EcO157 within half a
      day in wastewater from dairy lagoons. Although chemical, environmental and
      biological factors may be responsible for this decrease, we observed an 11-fold
      increase in native protozoa when wastewater was re-inoculated with 2*10(7) cells
      of EcO157/mL. These protozoa engulfed the green fluorescent protein labeled
      EcO157 within 2 hours after inoculation, but expelled vacuoles filled with live
      EcO157 cells within 3 days into surrounding wastewater, whereas other protozoa
      retained the EcO157-filled vacuoles for 7 days. EcO157 was not detected by
      confocal microscopy either inside or outside protozoa after 7 days. Mixed
      cultures of protozoa enriched from wastewater consumed EcO157 preferentially as
      compared to native aerobic bacteria, but failed to eliminate them when EcO157
      cells declined to 10(4)/mL. We isolated three protozoa from mixed cultures and
      typed them by 18S sequencing as Vorticella microstoma, Platyophyra sp. and
      Colpoda aspera. While all three protozoa internalized EcO157, only Platyophyra
      and Colpoda acted as predators. Similar to mixed cultures, these protozoa failed
      to eliminate EcO157 from PBS containing no other supplemental nutrients or prey.
      However, spiking PBS with cereal grass medium as nutrients induced predation of
      EcO157 by Platyophyra sp. after 3 days or enhanced predation by Colpoda after 5
      days. Therefore, attempts to enrich protozoa to decrease EcO157 from dairy
      lagoons, may correspond to an increase in protozoa similar to Vorticella and
      possibly facilitate transport of bacterial pathogens to food crops grown in
      proximity.

PMID- 21187935
TI  - Genes involved in the metabolism of poly-unsaturated fatty-acids (PUFA) and risk
      for Crohn's disease in children & young adults.
AB  - BACKGROUND AND OBJECTIVES: Epidemiological evidence for the role of
      polyunsaturated fatty-acids (PUFA) in Crohn's disease (CD) is unclear, although
      the key metabolite leucotriene B4 (LTB(4)) is closely linked to the inflammatory
      process. We hypothesized that inherited variation in key PUFA metabolic enzymes
      may modify susceptibility for CD. METHODS AND PRINCIPAL RESULTS: A case-control
      design was implemented at three pediatric gastroenterology clinics in Canada.
      Children <=20 yrs diagnosed with CD and controls were recruited. 19 single
      nucleotide polymorphisms (SNPs) across the ALOX5 (4) CYP4F3 (5) and CYP4F2 (10)
      genes, were genotyped. Associations between SNPs/haplotypes and CD were examined.
      A total of 431 cases and 507 controls were studied. The mean (+/-SD) age of the
      cases was 12.4 (+/-3.3) years. Most cases were male (56.4%), had ileo-colonic
      disease (L3+/-L4, 52.7%) and inflammatory behavior (B1+/-p, 87%) at diagnosis.
      One genotyped CYP4F3 SNP (rs2683037) not in Hardy-Weinberg Equilibrium was
      excluded. No associations with the remaining 4 CYP4F3 SNPs with CD were evident.
      However haplotype analysis revealed associations with a two-marker haplotype (TG)
      (rs3794987 & rs1290617) (p = 0.02; permuted p = 0.08). CYP4F2 SNPs, rs3093158 (OR
      (recessive) = 0.56, 95% CI = 0.35-0.89; p = 0.01), rs2074902 (OR (trend) = 1.26,
      95% CI = 1.00-1.60; p = 0.05), and rs2108622 (OR (recessive) = 1.6, 95% CI = 1.00
      2.57; p = 0.05) were significantly associated whereas rs1272 (OR (recessive) =
      0.58, 95% CI = 0.30-1.13; p = 0.10) showed suggestions for associations with CD.
      A haplotype comprising these 4 SNPs was significantly associated (p = 0.007,
      permuted p = 0.02) with CD. Associations with SNP rs3780901 in the ALOX5 gene
      were borderline non-significant (OR (dominant) = 1.29, 95% CI = 0.99-1.67; p =
      0.056). A haplotype comprising the 4 ALOX5 SNPs (TCAA, p = 0.036) was associated
      with CD, but did not withstand corrections for multiple comparisons (permuted p =
      0.14). CONCLUSIONS: Inherited variation in enzymes involved in the
      synthesis/metabolism of LTB(4) may be associated with CD. These findings
      implicate PUFA metabolism as a important pathway in the CD pathogenesis.

PMID- 21187936
TI  - Purinergic receptor functionality is necessary for infection of human hepatocytes
      by hepatitis delta virus and hepatitis B virus.
AB  - Hepatitis B virus (HBV) and hepatitis delta virus (HDV) are major sources of
      acute and chronic hepatitis. HDV requires the envelope proteins of HBV for the
      processes of assembly and infection of new cells. Both viruses are able to infect
      hepatocytes though previous studies have failed to determine the mechanism of
      entry into such cells. This study began with evidence that suramin, a symmetrical
      hexasulfated napthylurea, could block HDV entry into primary human hepatocytes
      (PHH) and was then extrapolated to incorporate findings of others that suramin is
      one of many compounds that can block activation of purinergic receptors. Thus
      other inhibitors, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate (PPADS) and
      brilliant blue G (BBG), both structurally unrelated to suramin, were tested and
      found to inhibit HDV and HBV infections of PHH. BBG, unlike suramin and PPADS, is
      known to be more specific for just one purinergic receptor, P2X7. These studies
      provide the first evidence that purinergic receptor functionality is necessary
      for virus entry. Furthermore, since P2X7 activation is known to be a major
      component of inflammatory responses, it is proposed that HDV and HBV attachment
      to susceptible cells, might also contribute to inflammation in the liver, that
      is, hepatitis.

PMID- 21187937
TI  - Exit mechanisms of the intracellular bacterium Ehrlichia.
AB  - BACKGROUND: The obligately intracellular bacterium Ehrlichia chaffeensis that
      resides in mononuclear phagocytes is the causative agent of human monocytotropic
      ehrlichiosis. Ehrlichia muris and Ixodes ovatus Ehrlichia (IOE) are agents of
      mouse models of ehrlichiosis. The mechanism by which Ehrlichia are transported
      from an infected host cell to a non-infected cell has not been demonstrated.
      METHODOLOGY/PRINCIPAL FINDINGS: Using fluorescence microscopy and transmission
      and scanning electron microscopy, we demonstrated that Ehrlichia was transported
      through the filopodia of macrophages during early stages of infection. If host
      cells were not present in the vicinity of an Ehrlichia-infected cell, the leading
      edge of the filopodium formed a fan-shaped structure filled with the pathogen.
      Formation of filopodia in the host macrophages was inhibited by cytochalasin D
      and ehrlichial transport were prevented due to the absence of filopodia
      formation. At late stages of infection the host cell membrane was ruptured, and
      the bacteria were released. CONCLUSIONS/SIGNIFICANCE: Ehrlichia are transported
      through the host cell filopodium during initial stages of infection, but are
      released by host cell membrane rupture during later stages of infection.

PMID- 21187939
TI  - High affinity allele for the gene of FCGR3A is risk factor for HIV infection and
      progression.
AB  - BACKGROUND: We investigated the genetics of Fc receptors, which function as
      activating receptors on immune cells and help to control HIV through antibody
      mediated cellular cytotoxicity. Thus, Fc receptors may be important for virus
      immunity but might also promote immune hyperactivation that would enhance
      infection. METHODOLOGY/PRINCIPAL FINDINGS: We measured abundance of low and high
      activity alleles in two Fc receptor genes, FCGR2A and FCGR3A, for persons with
      HIV disease, natural virus suppressors (HIV+, without disease) and healthy
      controls to show whether genotypes were associated with infection and disease.
      Individuals homozygous for the high activity allele of FCGR3A (158VV) were
      predominantly found among HIV progressors and this group was also skewed toward
      higher allele frequencies for the V158 variant. Both of the HIV positive groups
      (progressors and natural virus suppressors) had significantly higher frequencies
      of the V158 allele compared with uninfected controls. There were no apparent
      associations among FCGR2A alleles and HIV status. CONCLUSIONS/SIGNIFICANCE: Our
      results indicate that high activity alleles of FCGR3A may be risk factors for HIV
      infection or progression and we need to understand how allelic variants affect
      the balance between virus control and immune activation.

PMID- 21187940
TI  - An alternative alar cinch suture.
AB  - Nasal widening is commonly associated to maxillary osteotomies, but it is only
      partially dependent on the amount of skeletal movement. Techniques for
      controlling lateralization of the ala, including the alar base cinch technique,
      originally described by Millard, have been well reported by Collins and Epker and
      later modified by others. In this article, authors report the effect of a new
      alar cinch suture technique on a sample of 32 patients.

PMID- 21187938
TI  - Influenza pandemic waves under various mitigation strategies with 2009 H1N1 as a
      case study.
AB  - A significant feature of influenza pandemics is multiple waves of morbidity and
      mortality over a few months or years. The size of these successive waves depends
      on intervention strategies including antivirals and vaccination, as well as the
      effects of immunity gained from previous infection. However, the global vaccine
      manufacturing capacity is limited. Also, antiviral stockpiles are costly and
      thus, are limited to very few countries. The combined effect of antivirals and
      vaccination in successive waves of a pandemic has not been quantified. The effect
      of acquired immunity from vaccination and previous infection has also not been
      characterized. In times of a pandemic threat countries must consider the effects
      of a limited vaccine, limited antiviral use and the effects of prior immunity so
      as to adopt a pandemic strategy that will best aid the population. We developed a
      mathematical model describing the first and second waves of an influenza pandemic
      including drug therapy, vaccination and acquired immunity. The first wave model
      includes the use of antiviral drugs under different treatment profiles. In the
      second wave model the effects of antivirals, vaccination and immunity gained from
      the first wave are considered. The models are used to characterize the severity
      of infection in a population under different drug therapy and vaccination
      strategies, as well as school closure, so that public health policies regarding
      future influenza pandemics are better informed.

PMID- 21187941
TI  - Using biobrane: techniques to make life easier.
AB  - AIMS: To facilitate the use of Biobrane for those burn care practitioners not
      familiar with this material. METHODS: Two techniques have been developed through
      extensive use of Biobrane over many years, in both sheet and glove form. These
      techniques have been described and illustrated with photographs. RESULTS: The use
      of these techniques has allowed the corresponding author to markedly reduce
      operating time and to easily apply the material single-handedly. CONCLUSION:
      Biobrane is a biosynthetic skin substitute primarily designed for the definitive
      treatment of superficial partial-thickness to mid-dermal burn injury. Once
      experienced with its use, the material is quite ubiquitous. The described
      techniques will facilitate the use of Biobrane for those not familiar with it.

PMID- 21187942
TI  - Highly efficient human serum filtration with water-soluble nanoporous
      nanoparticles.
AB  - BACKGROUND: Human serum has the potential to become the most informative source
      of novel biomarkers, but its study is very difficult due to the incredible
      complexity of its molecular composition. We describe a novel tool based on
      biodegradable nanoporous nanoparticles (NPNPs) that allows the harvesting of low
      molecular-weight fractions of crude human serum or other biofluids. NPNPs with a
      diameter of 200 nm and pore size of a few nm were obtained by ultrasonication of
      nanoporous silicon. When incubated with a solution, the NPNPs harvest only the
      molecules small enough to be absorbed into the nanopores. Then they can be
      recovered by centrifugation and dissolved in water, making the harvested
      molecules available for further analyses. RESULTS: Fluorescence microscopy, gel
      electrophoresis, and mass spectrometry were used to show the enrichment of low
      molecular-weight fraction of serum under physiological conditions, with a cut-off
      of 13 kDa and an enrichment factor >50. CONCLUSION: From these findings, we
      conclude that ability to tune pore size, combined with the availability of
      hundreds of biomolecule cross-linkers, opens up new perspectives on complex
      biofluid analysis, discovery of biomarkers, and in situ drug delivery.

PMID- 21187943
TI  - Antibacterial properties of silver nanoparticles in three different sizes and
      their nanocomposites with a new waterborne polyurethane.
AB  - Silver nanoparticles (AgNPs) are strong bactericidal agents but they are also
      cytotoxic. Embedding them in a polymer matrix may reduce their cytotoxic effect.
      In the present study, AgNPs in three average sizes were tested for their
      antibacterial activities and cytotoxicity. Nanocomposites from a new waterborne
      polyetherurethane (PEU) ionomer and AgNPs were prepared without the use of any
      crosslinker. It was observed that the antibacterial activity of AgNPs against
      Escherichia coli started at the effective concentration of 0.1-1 ppm, while that
      against Staphylococcus aureus started at higher concentrations of 1-10 ppm.
      Cytotoxicity of AgNPs was observed at the concentration of 10 ppm. AgNPs with
      smaller average size showed greater antibacterial activity as well as
      cytotoxicity. The PEU synthesized in this study showed high tensile strength, and
      the addition of AgNPs at all sizes further increased its thermal stability. The
      delicate surface features of nanophases, however, were only observed in
      nanocomposites with either small-or medium-sized AgNPs. PEU-Ag nanocomposites had
      a strong bacteriostatic effect on the growth of E. coli and S. aureus. The
      proliferation of endothelial cells on PEU-Ag nanocomposites was enhanced, whereas
      the platelet adhesion was reduced. The expression of endothelial nitric oxide
      synthase gene was upregulated on PEU-Ag containing small-sized AgNPs (30 ppm) or
      medium-sized AgNPs (60 ppm). This effect was not as remarkable in nanocomposites
      from large-sized AgNPs. Overall, nanocomposites from the PEU and 60 ppm of the
      medium-sized (5 nm) AgNPs showed the best biocompatibility and antibacterial
      activity. Addition of smaller or larger AgNPs did not produce as substantial an
      effect in PEU, especially for the larger AgNPs.

PMID- 21187944
TI  - Ablation and optical third-order nonlinearities in Ag nanoparticles.
AB  - The optical damage associated with high intensity laser excitation of silver
      nanoparticles (NPs) was studied. In order to investigate the mechanisms of
      optical nonlinearity of a nanocomposite and their relation with its ablation
      threshold, a high-purity silica sample implanted with Ag ions was exposed to
      different nanosecond and picosecond laser irradiations. The magnitude and sign of
      picosecond refractive and absorptive nonlinearities were measured near and far
      from the surface plasmon resonance (SPR) of the Ag NPs with a self-diffraction
      technique. Saturable optical absorption and electronic polarization related to
      self-focusing were identified. Linear absorption is the main process involved in
      nanosecond laser ablation, but non-linearities are important for ultrashort
      picosecond pulses when the absorptive process become significantly dependent on
      the irradiance. We estimated that near the resonance, picosecond intraband
      transitions allow an expanded distribution of energy among the NPs, in comparison
      to the energy distribution resulting in a case of far from resonance, when the
      most important absorption takes place in silica. We measured important
      differences in the ablation threshold and we estimated that the high
      selectiveness of the SPR of Ag NPs as well as their corresponding optical
      nonlinearities can be strongly significant for laser-induced controlled
      explosions, with potential applications for biomedical photothermal processes.

PMID- 21187945
TI  - Characterization and in vivo evaluation of novel lipid-chlorambucil nanospheres
      prepared using a mixture of emulsifiers for parenteral administration.
AB  - PURPOSE: The purpose of the study was to develop and evaluate different lipid
      based formulations for parenteral administration, as potential novel carrier
      systems for lipophilic drugs, and to turn an unstable drug such as chlorambucil
      into a useful one. METHODS: A two-stage, high-pressure homogenizer was used to
      yield a very fine monodispersed lipid nanosphere. The strategy of combining egg
      yolk phospholipid and nonionic emulsifier (Lutrol F 68 and Tween 80) as an
      emulsifier mixture was adopted to increase safety and tolerance. The final lipid
      nanospheres, in a lipophilic mixture consisting of three components, monostearin,
      medium-chain triglycerides and soya oil, were evaluated for physicochemical
      properties, such as particle size, surface morphology, drug-entrapment
      efficiency, drug-loading capacity, lyophilization and in vivo drug-release
      behavior. RESULTS: A monodispersed lipid nanosphere with a mean particle size
      ranging from 90 to 150 nm was achieved. The optimized injectable cryoprotectants
      for lipid nanosphere were sucrose (7.5%) and mannitol (7.5%), which can stabilize
      the particle size (LD50) at approximately 129 nm after reconstitution. The
      results show that the formulation can effectively administer anticancer drugs and
      thus improve patient quality of life. CONCLUSIONS: The novel lipid nanosphere
      complex developed is a useful anticancer drug delivery vehicle for parenteral
      administration. The formulation strategy has the potential for the development of
      further methods of drug delivery for a wide variety of anticancer drugs.

PMID- 21187946
TI  - Sustained-release progesterone nanosuspension following intramuscular injection
      in ovariectomized rats.
AB  - The production of an intramuscular (IM) injection of natural progesterone would
      provide a safer solution than using semi synthetic progesterone. However,
      disadvantages such as low solubility and a short half life prevent the use of
      natural progesterone. In this study, we formulated a sustained release form of
      natural progesterone to be given as IM injection. A progesterone nanosuspension
      (PNS) was first developed and then dispersed in a thermosensitive gel matrix. The
      selected nanoparticles showed an average particle size of 267 nm and a zeta
      potential approaching-41 mV. The in vitro release profile of PNS from the F127
      plus methyl cellulose gel followed zero order kinetics and correlated linearly
      with the weight percentage of gel dissolved, demonstrating that the overall rate
      of release of PNS is controlled by dissolution of the pluronic F127/methyl
      cellulose (MC) gel (r2 > 0.99). The pharmacokinetic parameters of the PNS (6
      mg/mL) in pluronic F127/MC gel were evaluated in comparison with the control
      progesterone suspension. After the administration of PNS in F127/MC gel into the
      rats, a maximum serum concentration of 22.1 +/- 1.9 ng/mL was reached at a T(max)
      of 4.05 +/- 0.1 h. The terminal half life was 12.7 +/- 0.8 h. The area under the
      curve AUC0-infinity of the injected formula was 452.75 +/- 42.8 ng.h/mL and the
      total mean residence time was 18.57 +/- 1.44 h. The PNS in gel was significantly
      different from the control in rate and extent at P < 0.001. The natural
      progesterone which was nanosized and formulated in a thermosensitive gel
      significantly sustained the action of natural progesterone so that it could be
      injected every 36 h instead of every day. Moreover, this formula is expected to
      provide a much safer choice than the use of semi-synthetic progesterone.

PMID- 21187947
TI  - Intracellular heavy metal nanoparticle storage: progressive accumulation within
      lymph nodes with transformation from chronic inflammation to malignancy.
AB  - A 25-year-old man had complained of sudden fever spikes for two years and his
      blood tests were within the normal range. In 1993, a surgical biopsy of swollen
      left inguinal lymph nodes was negative for malignancy, but showed reactive
      lymphadenitis and widespread sinus histiocytosis. A concomitant needle biopsy of
      the periaortic lymph nodes and a bone marrow aspirate were also negative. In
      1994, after an emergency hospital admission because of a sport-related thoracic
      trauma, a right inguinal lymph node biopsy demonstrated Hodgkin's lymphoma Stage
      IVB (scleronodular mixed cell subtype). Although it was improved by chemotherapy,
      the disease suddenly relapsed, and a further lymph node biopsy was performed in
      1998 confirming the same diagnosis. Despite further treatment, the patient died
      of septic shock in 2004, at the age of 38 years. Retrospective analysis of the
      various specimens showed intracellular heavy metal nanoparticles within lymph
      node, bone marrow, and liver samples by field emission gun environmental scanning
      electron microscopy and energy dispersive spectroscopy. Heavy metals from
      environmental pollution may accumulate in sites far from the entry route and, in
      genetically conditioned individuals with tissue specificity, may act as cofactors
      for chronic inflammation or even malignant transformation. The present anecdotal
      report highlights the need for further pathologic ultrastructural investigations
      using serial samples and the possible role of intracellular nanoparticles in
      human disease.

PMID- 21187948
TI  - L-tyrosine-loaded nanoparticles increase the antitumoral activity of direct
      electric current in a metastatic melanoma cell model.
AB  - Inhibition of tumor growth induced by treatment with direct electric current (DC)
      has been reported in several models. One of the mechanisms responsible for the
      antitumoral activity of DC is the generation of oxidative species, known as
      chloramines. With the aim of increasing chloramine production in the electrolytic
      medium and optimizing the antitumoral effects of DC, poly(E-caprolactone) (PCL)
      nanoparticles (NPs) loaded with the amino acid tyrosine were obtained. The
      physical-chemical characterization showed that the NPs presented size in
      nanometric range and monomodal distribution. A slightly negative electrokinetic
      potential was also found in both blank NPs and L-tyrosine-loaded PCL NPs. The
      yield of the loading process was approximately 50%. Within 3 h of dissolution
      assay, a burst release of about 80% L-tyrosine was obtained. The in vitro
      cytotoxicity of DC was significantly increased when associated with L-tyrosine
      loaded NPs, using a murine multidrug-resistant melanoma cell line model. This
      study showed that the use of the combination of nanotechnology and DC has a
      promising antineoplastic potential and opens a new perspective in cancer therapy.

PMID- 21187949
TI  - Immunotargeting of collagenase on thrombus.
AB  - In this study, we aimed to develop a thrombus-targeting delivery system of
      collagenase bound to a monoclonal antibody, and to investigate the thrombolysis
      of an immune-conjugate in vitro and in vivo as well as the targeting effect. We
      prepared the immunizing conjugation of collagenase by the 1-ethyl-3-(3
      dimethylaminopropyl)-carbodiimide (EDCI) method. In order to conjugate
      collagenase and a monoclonal antibody, bovine serum albumin was used as a linker,
      increasing the number of collagenase molecules carried and keeping collagenase
      and the monoclonal antibody active. In vitro thrombolysis experiments showed that
      collagenase had a strong dissolving effect on collagen-embolus within 24 hours.
      We established a rabbit pulmonary embolism model to investigate the thrombolysis
      effect of collagenase and collagenase immunizing conjugation in vivo. Our results
      revealed a significant difference between collagenase and collagenase immunizing
      conjugation (P < 0.05). We also established a rabbit ear edge vein model to
      investigate the active target of collagenase immunizing conjugation. We found
      that collagenase immunizing conjugation had active targets, and had a strong
      ability to dissolve organized thrombi. In conclusion, the thrombus-targeting
      delivery system of collagenase we developed has active targeting effects on
      thrombi.

PMID- 21187950
TI  - Reconstructed ancestral sequences improve pathogen identification using
      resequencing DNA microarrays.
AB  - We describe the benefit of using reconstructed ancestral sequences (RAS) on
      resequencing microarrays for rapid pathogen identification, with
      Enterobacteriaceae rpoB sequences as a model. Our results demonstrate a sharp
      improvement of call rate and accuracy when using RASs as compared to extant
      sequences. This improvement was attributed to the lower sequence divergence of
      RASs, which also expanded the sequence space covered by the microarray. Extension
      of this novel microarray design strategy to viruses, antimicrobial resistance
      elements or toxins is straightforward.

PMID- 21187951
TI  - Identification and interpretation of longitudinal gene expression changes in
      trauma.
AB  - RATIONALE: The relationship between leukocyte gene expression and recovery of
      respiratory function after injury may provide information on the etiology of
      multiple organ dysfunction. OBJECTIVES: To find a list of genes for which
      expression after injury predicts respiratory recovery, and to identify which
      networks and pathways characterize these genes. METHODS: Blood was sampled at 12
      hours and at 1, 4, 7, 21 and 28 days from 147 patients who had been admitted to
      the hospital after blunt trauma. Leukocyte gene expression was measured using
      Affymetrix oligonucleotide arrays. A linear model, fit to each probe-set
      expression value, was used to impute the gene expression trajectory over the
      entire follow-up period. The proportional hazards model score test was used to
      calculate the statistical significance of each probe-set trajectory in predicting
      respiratory recovery. A list of genes was determined such that the expected
      proportion of false positive results was less than 10%. These genes were compared
      to the Gene Ontology for 'response to stimulus' and, using Ingenuity software,
      were mapped into networks and pathways. MEASUREMENTS AND MAIN RESULTS: The median
      time to respiratory recovery was 6 days. There were 170 probe-sets representing
      135 genes that were found to be related to respiratory recovery. These genes
      could be mapped to nine networks. Two known pathways that were activated were
      antigen processing and presentation and JAK-signaling. CONCLUSIONS: The
      examination of the relationship of gene expression over time with a patient's
      clinical course can provide information which may be useful in determining the
      mechanism of recovery or lack of recovery after severe injury.

PMID- 21187952
TI  - Closing the mind's eye: incoming luminance signals disrupt visual imagery.
AB  - Mental imagery has been associated with many cognitive functions, both high and
      low-level. Despite recent scientific advances, the contextual and environmental
      conditions that most affect the mechanisms of visual imagery remain unclear. It
      has been previously shown that the greater the level of background luminance the
      weaker the effect of imagery on subsequent perception. However, in these
      experiments it was unclear whether the luminance was affecting imagery generation
      or storage of a memory trace. Here, we report that background luminance can
      attenuate both mental imagery generation and imagery storage during an unrelated
      cognitive task. However, imagery generation was more sensitive to the degree of
      luminance. In addition, we show that these findings were not due to differential
      dark adaptation. These results suggest that afferent visual signals can interfere
      with both the formation and priming-memory effects associated with visual
      imagery. It follows that background luminance may be a valuable tool for
      investigating imagery and its role in various cognitive and sensory processes.

PMID- 21187953
TI  - Three ways of combining genotyping and resequencing in case-control association
      studies.
AB  - We describe three statistical results that we have found to be useful in case
      control genetic association testing. All three involve combining the discovery of
      novel genetic variants, usually by sequencing, with genotyping methods that
      recognize previously discovered variants. We first consider expanding the list of
      known variants by concentrating variant-discovery in cases. Although the naive
      inclusion of cases-only sequencing data would create a bias, we show that some
      sequencing data may be retained, even if controls are not sequenced. Furthermore,
      for alleles of intermediate frequency, cases-only sequencing with bias-correction
      entails little if any loss of power, compared to dividing the same sequencing
      effort among cases and controls. Secondly, we investigate more strongly focused
      variant discovery to obtain a greater enrichment for disease-related variants. We
      show how case status, family history, and marker sharing enrich the discovery set
      by increments that are multiplicative with penetrance, enabling the preferential
      discovery of high-penetrance variants. A third result applies when sequencing is
      the primary means of counting alleles in both cases and controls, but a
      supplementary pooled genotyping sample is used to identify the variants that are
      very rare. We show that this raises no validity issues, and we evaluate a less
      expensive and more adaptive approach to judging rarity, based on group-specific
      variants. We demonstrate the important and unusual caveat that this method
      requires equal sample sizes for validity. These three results can be used to more
      efficiently detect the association of rare genetic variants with disease.

PMID- 21187954
TI  - Lithium improves hippocampal neurogenesis, neuropathology and cognitive functions
      in APP mutant mice.
AB  - BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder
      characterized by progressive deterioration of cognitive functions, extracellular
      beta-amyloid (Abeta) plaques and intracellular neurofibrillary tangles within
      neocortex and hippocampus. Adult hippocampal neurogenesis plays an important role
      in learning and memory processes and its abnormal regulation might account for
      cognitive impairments associated with AD. METHODOLOGY/PRINCIPAL FINDINGS: The
      double transgenic (Tg) CRND8 mice (overexpressing the Swedish and Indiana
      mutations in the human amyloid precursor protein), aged 2 and 6 months, were used
      to examine in vivo the effects of 5 weeks lithium treatment. BrdU labelling
      showed a decreased neurogenesis in the subgranular zone of Tg mice compared to
      non-Tg mice. The decrease of hippocampal neurogenesis was accompanied by
      behavioural deficits and worsened with age and pathology severity. The
      differentiation into neurons and maturation of the proliferating cells were also
      markedly impaired in the Tg mice. Lithium treatment to 2-month-old Tg mice
      significantly stimulated the proliferation and neuron fate specification of
      newborn cells and fully counteracted the transgene-induced impairments of
      cognitive functions. The drug, by the inhibition of GSK-3beta and subsequent
      activation of Wnt/beta-catenin signalling promoted hippocampal neurogenesis.
      Finally, the data show that the lithium's ability to stimulate neurogenesis and
      cognitive functions was lost in the aged Tg mice, thus indicating that the
      lithium-induced facilitation of neurogenesis and cognitive functions declines as
      brain Abeta deposition and pathology increases. CONCLUSIONS: Lithium, when given
      on time, stimulates neurogenesis and counteracts AD-like pathology.

PMID- 21187955
TI  - Mutations in SCG10 are not involved in Hirschsprung disease.
AB  - Hirschsprung disease (HSCR) is a congenital malformation characterized by the
      absence of enteric neurons in the distal part of the colon. Several genes have
      been implicated in the development of this disease that together account for 20%
      of all cases, implying that other genes are involved. Since HSCR is frequently
      associated with other congenital malformations, the functional characterization
      of the proteins encoded by the genes involved in these syndromes can provide
      insights into the protein-network involved in HSCR development. Recently, we
      found that KBP, encoded by the gene involved in a HSCR- associated syndrome
      called Goldberg-Shprintzen syndrome, interacts with SCG10, a stathmin-like
      protein. To determine if SCG10 is involved in the etiology of HSCR, we determined
      SCG10 expression levels during development and screened 85 HSCR patients for
      SCG10 mutations. We showed that SCG10 expression increases during development but
      no germline mutation was found in any of these patients. In conclusion, this
      study shows that SCG10 is not directly implicated in HSCR development. However,
      an indirect involvement of SCG10 cannot be ruled out as this can be due to a
      secondary effect caused by its direct interactors.

PMID- 21187956
TI  - Towards universal structure-based prediction of class II MHC epitopes for diverse
      allotypes.
AB  - The binding of peptide fragments of antigens to class II MHC proteins is a
      crucial step in initiating a helper T cell immune response. The discovery of
      these peptide epitopes is important for understanding the normal immune response
      and its misregulation in autoimmunity and allergies and also for vaccine design.
      In spite of their biomedical importance, the high diversity of class II MHC
      proteins combined with the large number of possible peptide sequences make
      comprehensive experimental determination of epitopes for all MHC allotypes
      infeasible. Computational methods can address this need by predicting epitopes
      for a particular MHC allotype. We present a structure-based method for predicting
      class II epitopes that combines molecular mechanics docking of a fully flexible
      peptide into the MHC binding cleft followed by binding affinity prediction using
      a machine learning classifier trained on interaction energy components calculated
      from the docking solution. Although the primary advantage of structure-based
      prediction methods over the commonly employed sequence-based methods is their
      applicability to essentially any MHC allotype, this has not yet been convincingly
      demonstrated. In order to test the transferability of the prediction method to
      different MHC proteins, we trained the scoring method on binding data for
      DRB1*0101 and used it to make predictions for multiple MHC allotypes with
      distinct peptide binding specificities including representatives from the other
      human class II MHC loci, HLA-DP and HLA-DQ, as well as for two murine allotypes.
      The results showed that the prediction method was able to achieve significant
      discrimination between epitope and non-epitope peptides for all MHC allotypes
      examined, based on AUC values in the range 0.632-0.821. We also discuss how
      accounting for peptide binding in multiple registers to class II MHC largely
      explains the systematically worse performance of prediction methods for class II
      MHC compared with those for class I MHC based on quantitative prediction
      performance estimates for peptide binding to class II MHC in a fixed register.

PMID- 21187957
TI  - Skeletal muscle NADPH oxidase is increased and triggers stretch-induced damage in
      the mdx mouse.
AB  - Recent studies have shown that oxidative stress contributes to the pathogenesis
      of muscle damage in dystrophic (mdx) mice. In this study we have investigated the
      role of NADPH oxidase as a source of the oxidative stress in these mice. The
      NADPH oxidase subunits gp91(phox), p67(phox) and rac 1 were increased 2-3 fold in
      tibilais anterior muscles from mdx mice compared to wild type. Importantly, this
      increase occurred in 19 day old mice, before the onset of muscle necrosis and
      inflammation, suggesting that NADPH oxidase is an important source of oxidative
      stress in mdx muscle. In muscles from 9 week old mdx mice, gp91(phox) and
      p67(phox) were increased 3-4 fold and NADPH oxidase superoxide production was 2
      times greater than wild type. In single fibers from mdx muscle NADPH oxidase
      subunits were all located on or near the sarcolemma, except for p67(phox),which
      was expressed in the cytosol. Pharmacological inhibition of NADPH oxidase
      significantly reduced the intracellular Ca(2+) rise following stretched
      contractions in mdx single fibers, and also attenuated the loss of muscle force.
      These results suggest that NADPH oxidase is a major source of reactive oxygen
      species in dystrophic muscle and its enhanced activity has a stimulatory effect
      on stretch-induced Ca(2+) entry, a key mechanism for muscle damage and functional
      impairment.

PMID- 21187958
TI  - Hyperpolarization-activated current (I(h)) in ganglion-cell photoreceptors.
AB  - Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the
      photopigment melanopsin and serve as the primary retinal drivers of non-image
      forming visual functions such as circadian photoentrainment, the pupillary light
      reflex, and suppression of melatonin production in the pineal. Past
      electrophysiological studies of these cells have focused on their intrinsic
      photosensitivity and synaptic inputs. Much less is known about their voltage
      gated channels and how these might shape their output to non-image-forming visual
      centers. Here, we show that rat ipRGCs retrolabeled from the suprachiasmatic
      nucleus (SCN) express a hyperpolarization-activated inwardly-rectifying current
      (I(h)). This current is blocked by the known I(h) blockers ZD7288 and
      extracellular cesium. As in other systems, including other retinal ganglion
      cells, I(h) in ipRGCs is characterized by slow kinetics and a slightly greater
      permeability for K(+) than for Na(+). Unlike in other systems, however, I(h) in
      ipRGCs apparently does not actively contribute to resting membrane potential. We
      also explore non-specific effects of the common I(h) blocker ZD7288 on rebound
      depolarization and evoked spiking and discuss possible functional roles of I(h)
      in non-image-forming vision. This study is the first to characterize I(h) in a
      well-defined population of retinal ganglion cells, namely SCN-projecting ipRGCs.

PMID- 21187959
TI  - Effects of combinatorial treatment with pituitary adenylate cyclase activating
      peptide and human mesenchymal stem cells on spinal cord tissue repair.
AB  - The aim of this study is to understand if human mesenchymal stem cells (hMSCs)
      and neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) have
      synergistic protective effect that promotes functional recovery in rats with
      severe spinal cord injury (SCI). To evaluate the effect of delayed combinatorial
      therapy of PACAP and hMSCs on spinal cord tissue repair, we used the immortalized
      hMSCs that retain their potential of neuronal differentiation under the
      stimulation of neurogenic factors and possess the properties for the production
      of several growth factors beneficial for neural cell survival. The results
      indicated that delayed treatment with PACAP and hMSCs at day 7 post SCI increased
      the remaining neuronal fibers in the injured spinal cord, leading to better
      locomotor functional recovery in SCI rats when compared to treatment only with
      PACAP or hMSCs. Western blotting also showed that the levels of antioxidant
      enzymes, Mn-superoxide dismutase (MnSOD) and peroxiredoxin-1/6 (Prx-1 and Prx-6),
      were increased at the lesion center 1 week after the delayed treatment with the
      combinatorial therapy when compared to that observed in the vehicle-treated
      control. Furthermore, in vitro studies showed that co-culture with hMSCs in the
      presence of PACAP not only increased a subpopulation of microglia expressing
      galectin-3, but also enhanced the ability of astrocytes to uptake extracellular
      glutamate. In summary, our in vivo and in vitro studies reveal that delayed
      transplantation of hMSCs combined with PACAP provides trophic molecules to
      promote neuronal cell survival, which also foster beneficial microenvironment for
      endogenous glia to increase their neuroprotective effect on the repair of injured
      spinal cord tissue.

PMID- 21187960
TI  - Different temporal structure for form versus surface cortical color systems-
      evidence from chromatic non-linear VEP.
AB  - Physiological studies of color processing have typically measured responses to
      spatially varying chromatic stimuli such as gratings, while psychophysical
      studies of color include color naming, color and light, as well as spatial and
      temporal chromatic sensitivities. This raises the question of whether we have one
      or several cortical color processing systems. Here we show from non-linear
      analysis of human visual evoked potentials (VEP) the presence of distinct and
      independent temporal signatures for form and surface color processing. Surface
      color stimuli produced most power in the second order Wiener kernel, indicative
      of a slowly recovering neural system, while chromatic form stimulation produced
      most power in the first order kernel (showing rapid recovery). We find end
      spectral saturation-dependent signals, easily separable from achromatic signals
      for surface color stimuli. However physiological responses to form color stimuli,
      though varying somewhat with saturation, showed similar waveform components.
      Lastly, the spectral dependence of surface and form color VEP was different, with
      the surface color responses almost vanishing with yellow-grey isoluminant
      stimulation whereas the form color VEP shows robust recordable signals across all
      hues. Thus, surface and form colored stimuli engage different neural systems
      within cortex, pointing to the need to establish their relative contributions
      under the diverse chromatic stimulus conditions used in the literature.

PMID- 21187961
TI  - Origin and history of mitochondrial DNA lineages in domestic horses.
AB  - Domestic horses represent a genetic paradox: although they have the greatest
      number of maternal lineages (mtDNA) of all domestic species, their paternal
      lineages are extremely homogeneous on the Y-chromosome. In order to address their
      huge mtDNA variation and the origin and history of maternal lineages in domestic
      horses, we analyzed 1961 partial d-loop sequences from 207 ancient remains and
      1754 modern horses. The sample set ranged from Alaska and North East Siberia to
      the Iberian Peninsula and from the Late Pleistocene to modern times. We found a
      panmictic Late Pleistocene horse population ranging from Alaska to the Pyrenees.
      Later, during the Early Holocene and the Copper Age, more or less separated sub
      populations are indicated for the Eurasian steppe region and Iberia. Our data
      suggest multiple domestications and introgressions of females especially during
      the Iron Age. Although all Eurasian regions contributed to the genetic pedigree
      of modern breeds, most haplotypes had their roots in Eastern Europe and Siberia.
      We found 87 ancient haplotypes (Pleistocene to Mediaeval Times); 56 of these
      haplotypes were also observed in domestic horses, although thus far only 39
      haplotypes have been confirmed to survive in modern breeds. Thus, at least
      seventeen haplotypes of early domestic horses have become extinct during the last
      5,500 years. It is concluded that the large diversity of mtDNA lineages is not a
      product of animal breeding but, in fact, represents ancestral variability.

PMID- 21187962
TI  - Order through disorder: hyper-mobile C-terminal residues stabilize the folded
      state of a helical peptide. a molecular dynamics study.
AB  - Conventional wisdom has it that the presence of disordered regions in the three
      dimensional structures of polypeptides not only does not contribute significantly
      to the thermodynamic stability of their folded state, but, on the contrary, that
      the presence of disorder leads to a decrease of the corresponding proteins'
      stability. We have performed extensive 3.4 us long folding simulations (in
      explicit solvent and with full electrostatics) of an undecamer peptide of
      experimentally known helical structure, both with and without its disordered
      (four residue long) C-terminal tail. Our simulations clearly indicate that the
      presence of the apparently disordered (in structural terms) C-terminal tail,
      increases the thermodynamic stability of the peptide's folded (helical) state.
      These results show that at least for the case of relatively short peptides, the
      interplay between thermodynamic stability and the apparent structural stability
      can be rather subtle, with even disordered regions contributing significantly to
      the stability of the folded state. Our results have clear implications for the
      understanding of peptide energetics and the design of foldable peptides.

PMID- 21187963
TI  - The Salmonella genomic island 1 is specifically mobilized in trans by the IncA/C
      multidrug resistance plasmid family.
AB  - BACKGROUND: The Salmonella genomic island 1 (SGI1) is a Salmonella enterica
      derived integrative mobilizable element (IME) containing various complex multiple
      resistance integrons identified in several S. enterica serovars and in Proteus
      mirabilis. Previous studies have shown that SGI1 transfers horizontally by in
      trans mobilization in the presence of the IncA/C conjugative helper plasmid pR55.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, we report the ability of different
      prevalent multidrug resistance (MDR) plasmids including extended-spectrum beta
      lactamase (ESBL) gene-carrying plasmids to mobilize the multidrug resistance
      genomic island SGI1. Through conjugation experiments, none of the 24 conjugative
      plasmids tested of the IncFI, FII, HI2, I1, L/M, N, P incompatibility groups were
      able to mobilize SGI1 at a detectable level (transfer frequency <10(-9)). In our
      collection, ESBL gene-carrying plasmids were mainly from the IncHI2 and I1 groups
      and thus were unable to mobilize SGI1. However, the horizontal transfer of SGI1
      was shown to be specifically mediated by conjugative helper plasmids of the broad
      host-range IncA/C incompatibility group. Several conjugative IncA/C MDR plasmids
      as well as the sequenced IncA/C reference plasmid pRA1 of 143,963 bp were shown
      to mobilize in trans SGI1 from a S. enterica donor to the Escherichia coli
      recipient strain. Depending on the IncA/C plasmid used, the conjugative transfer
      of SGI1 occurred at frequencies ranging from 10(-3) to 10(-6) transconjugants per
      donor. Of particular concern, some large IncA/C MDR plasmids carrying the
      extended-spectrum cephalosporinase bla(CMY-2) gene were shown to mobilize in
      trans SGI1. CONCLUSIONS/SIGNIFICANCE: The ability of the IncA/C MDR plasmid
      family to mobilize SGI1 could contribute to its spread by horizontal transfer
      among enteric pathogens. Moreover, the increasing prevalence of IncA/C plasmids
      in MDR S. enterica isolates worldwide has potential implications for the epidemic
      success of the antibiotic resistance genomic island SGI1 and its close
      derivatives.

PMID- 21187964
TI  - Spatio-temporal data comparisons for global highly pathogenic avian influenza
      (HPAI) H5N1 outbreaks.
AB  - Highly pathogenic avian influenza subtype H5N1 is a zoonotic disease and control
      of the disease is one of the highest priority in global health. Disease
      surveillance systems are valuable data sources for various researches and
      management projects, but the data quality has not been paid much attention in
      previous studies. Based on data from two commonly used databases (Office
      International des Epizooties (OIE) and Food and Agriculture Organization of the
      United Nations (FAO)) of global HPAI H5N1 outbreaks during the period of 2003
      2009, we examined and compared their patterns of temporal, spatial and spatio
      temporal distributions for the first time. OIE and FAO data showed similar trends
      in temporal and spatial distributions if they were considered separately.
      However, more advanced approaches detected a significant difference in joint
      spatio-temporal distribution. Because of incompleteness for both OIE and FAO
      data, an integrated dataset would provide a more complete picture of global HPAI
      H5N1 outbreaks. We also displayed a mismatching profile of global HPAI H5N1
      outbreaks and found that the degree of mismatching was related to the epidemic
      severity. The ideas and approaches used here to assess spatio-temporal data on
      the same disease from different sources are useful for other similar studies.

PMID- 21187965
TI  - Classification of drugs based on properties of sodium channel inhibition: a
      comparative automated patch-clamp study.
AB  - BACKGROUND: There is only one established drug binding site on sodium channels.
      However, drug binding of sodium channels shows extreme promiscuity: ~25% of
      investigated drugs have been found to potently inhibit sodium channels. The
      structural diversity of these molecules suggests that they may not share the
      binding site, and/or the mode of action. Our goal was to attempt classification
      of sodium channel inhibitors by measuring multiple properties of inhibition in
      electrophysiology experiments. We also aimed to investigate if different
      properties of inhibition correlate with specific chemical properties of the
      compounds. METHODOLOGY/PRINCIPAL FINDINGS: A comparative electrophysiological
      study of 35 compounds, including classic sodium channel inhibitors
      (anticonvulsants, antiarrhythmics and local anesthetics), as well as
      antidepressants, antipsychotics and neuroprotective agents, was carried out using
      rNav1.2 expressing HEK-293 cells and the QPatch automatic patch-clamp instrument.
      In the multi-dimensional space defined by the eight properties of inhibition
      (resting and inactivated affinity, potency, reversibility, time constants of
      onset and offset, use-dependence and state-dependence), at least three distinct
      types of inhibition could be identified; these probably reflect distinct modes of
      action. The compounds were clustered similarly in the multi-dimensional space
      defined by relevant chemical properties, including measures of lipophilicity,
      aromaticity, molecular size, polarity and electric charge. Drugs of the same
      therapeutic indication typically belonged to the same type. We identified
      chemical properties, which were important in determining specific properties of
      inhibition. State-dependence correlated with lipophilicity, the ratio of the
      neutral form of molecules, and aromaticity: We noticed that the highly state
      dependent inhibitors had at least two aromatic rings, logP>4.0, and pKa<8.0.
      CONCLUSIONS/SIGNIFICANCE: The correlations of inhibition properties both with
      chemical properties and therapeutic profiles would not have been evident through
      the sole determination of IC(50); therefore, recording multiple properties of
      inhibition may allow improved prediction of therapeutic usefulness.

PMID- 21187966
TI  - The prevalence and regulation of antisense transcripts in Schizosaccharomyces
      pombe.
AB  - A strand-specific transcriptome sequencing strategy, directional ligation
      sequencing or DeLi-seq, was employed to profile antisense transcriptome of
      Schizosaccharomyces pombe. Under both normal and heat shock conditions, we found
      that polyadenylated antisense transcripts are broadly expressed while distinct
      expression patterns were observed for protein-coding and non-coding loci.
      Dominant antisense expression is enriched in protein-coding genes involved in
      meiosis or stress response pathways. Detailed analyses further suggest that
      antisense transcripts are independently regulated with respect to their sense
      transcripts, and diverse mechanisms might be potentially involved in the
      biogenesis and degradation of antisense RNAs. Taken together, antisense
      transcription may have profound impacts on global gene regulation in S. pombe.

PMID- 21187967
TI  - The influence of natural barriers in shaping the genetic structure of Maharashtra
      populations.
AB  - BACKGROUND: The geographical position of Maharashtra state makes it rather
      essential to study the dispersal of modern humans in South Asia. Several
      hypotheses have been proposed to explain the cultural, linguistic and
      geographical affinity of the populations living in Maharashtra state with other
      South Asian populations. The genetic origin of populations living in this state
      is poorly understood and hitherto been described at low molecular resolution
      level. METHODOLOGY/PRINCIPAL FINDINGS: To address this issue, we have analyzed
      the mitochondrial DNA (mtDNA) of 185 individuals and NRY (non-recombining region
      of Y chromosome) of 98 individuals belonging to two major tribal populations of
      Maharashtra, and compared their molecular variations with that of 54 South Asian
      contemporary populations of adjacent states. Inter and intra population
      comparisons reveal that the maternal gene pool of Maharashtra state populations
      is composed of mainly South Asian haplogroups with traces of east and west
      Eurasian haplogroups, while the paternal haplogroups comprise the South Asian as
      well as signature of near eastern specific haplogroup J2a.
      CONCLUSIONS/SIGNIFICANCE: Our analysis suggests that Indian populations,
      including Maharashtra state, are largely derived from Paleolithic ancient
      settlers; however, a more recent (~10 Ky older) detectable paternal gene flow
      from west Asia is well reflected in the present study. These findings reveal
      movement of populations to Maharashtra through the western coast rather than
      mainland where Western Ghats-Vindhya Mountains and Narmada-Tapti rivers might
      have acted as a natural barrier. Comparing the Maharastrian populations with
      other South Asian populations reveals that they have a closer affinity with the
      South Indian than with the Central Indian populations.

PMID- 21187968
TI  - Environmental effects on temperature stress resistance in the tropical butterfly
      Bicyclus anynana.
AB  - BACKGROUND: The ability to withstand thermal stress is considered to be of
      crucial importance for individual fitness and species' survival. Thus, organisms
      need to employ effective mechanisms to ensure survival under stressful thermal
      conditions, among which phenotypic plasticity is considered a particularly quick
      and effective one. METHODOLOGY/PRINCIPAL FINDINGS: In a series of experiments we
      here investigate phenotypic adjustment in temperature stress resistance following
      environmental manipulations in the butterfly Bicyclus anynana. Cooler compared to
      warmer acclimation temperatures generally increased cold but decreased heat
      stress resistance and vice versa. In contrast, short-time hardening responses
      revealed more complex patterns, with, e.g., cold stress resistance being highest
      at intermediate hardening temperatures. Adult food stress had a negative effect
      on heat but not on cold stress resistance. Additionally, larval feeding treatment
      showed interactive effects with adult feeding for heat but not for cold stress
      resistance, indicating that nitrogenous larval resources may set an upper limit
      to performance under heat stress. In contrast to expectations, cold resistance
      slightly increased during the first eight days of adult life. Light cycle had
      marginal effects on temperature stress resistance only, with cold resistance
      tending to be higher during daytime and thus active periods.
      CONCLUSIONS/SIGNIFICANCE: Our results highlight that temperature-induced
      plasticity provides an effective tool to quickly and strongly modulate
      temperature stress resistance, and that such responses are readily reversible.
      However, resistance traits are not only affected by ambient temperature, but also
      by, e.g., food availability and age, making their measurement challenging. The
      latter effects are largely underexplored and deserve more future attention. Owing
      to their magnitude, plastic responses in thermal tolerance should be incorporated
      into models trying to forecast effects of global change on extant biodiversity.

PMID- 21187969
TI  - A serum factor induces insulin-independent translocation of GLUT4 to the cell
      surface which is maintained in insulin resistance.
AB  - In response to insulin, glucose transporter GLUT4 translocates from intracellular
      compartments towards the plasma membrane where it enhances cellular glucose
      uptake. Here, we show that sera from various species contain a factor that dose
      dependently induces GLUT4 translocation and glucose uptake in 3T3-L1 adipocytes,
      human adipocytes, myoblasts and myotubes. Notably, the effect of this factor on
      GLUT4 is fully maintained in insulin-resistant cells. Our studies demonstrate
      that the serum-induced increase in cell surface GLUT4 levels is not due to
      inhibition of its internalization and is not mediated by insulin, PDGF, IGF-1, or
      HGF. Similarly to insulin, serum also augments cell surface levels of GLUT1 and
      TfR. Remarkably, the acute effect of serum on GLUT4 is largely additive to that
      of insulin, while it also sensitizes the cells to insulin. In accordance with
      these findings, serum does not appear to activate the same repertoire of
      downstream signaling molecules that are implicated in insulin-induced GLUT4
      translocation. We conclude that in addition to insulin, at least one other
      biological proteinaceous factor exists that contributes to GLUT4 regulation and
      still functions in insulin resistance. The challenge now is to identify this
      factor.

PMID- 21187970
TI  - Marginal level dystrophin expression improves clinical outcome in a strain of
      dystrophin/utrophin double knockout mice.
AB  - Inactivation of all utrophin isoforms in dystrophin-deficient mdx mice results in
      a strain of utrophin knockout mdx (uko/mdx) mice. Uko/mdx mice display severe
      clinical symptoms and die prematurely as in Duchenne muscular dystrophy (DMD)
      patients. Here we tested the hypothesis that marginal level dystrophin expression
      may improve the clinical outcome of uko/mdx mice. It is well established that
      mdx3cv (3cv) mice express a near-full length dystrophin protein at ~5% of the
      normal level. We crossed utrophin-null mutation to the 3cv background. The
      resulting uko/3cv mice expressed the same level of dystrophin as 3cv mice but
      utrophin expression was completely eliminated. Surprisingly, uko/3cv mice showed
      a much milder phenotype. Compared to uko/mdx mice, uko/3cv mice had significantly
      higher body weight and stronger specific muscle force. Most importantly, uko/3cv
      outlived uko/mdx mice by several folds. Our results suggest that a threshold
      level dystrophin expression may provide vital clinical support in a severely
      affected DMD mouse model. This finding may hold clinical implications in
      developing novel DMD therapies.

PMID- 21187971
TI  - Tiling histone H3 lysine 4 and 27 methylation in zebrafish using high-density
      microarrays.
AB  - BACKGROUND: Uncovering epigenetic states by chromatin immunoprecipitation and
      microarray hybridization (ChIP-chip) has significantly contributed to the
      understanding of gene regulation at the genome-scale level. Many studies have
      been carried out in mice and humans; however limited high-resolution information
      exists to date for non-mammalian vertebrate species. PRINCIPAL FINDINGS: We
      report a 2.1-million feature high-resolution Nimblegen tiling microarray for ChIP
      chip interrogations of epigenetic states in zebrafish (Danio rerio). The array
      covers 251 megabases of the genome at 92 base-pair resolution. It includes ~15 kb
      of upstream regulatory sequences encompassing all RefSeq promoters, and over 5 kb
      in the 5' end of coding regions. We identify with high reproducibility, in a
      fibroblast cell line, promoters enriched in H3K4me3, H3K27me3 or co-enriched in
      both modifications. ChIP-qPCR and sequential ChIP experiments validate the ChIP
      chip data and support the co-enrichment of trimethylated H3K4 and H3K27 on a
      subset of genes. H3K4me3- and/or H3K27me3-enriched genes are associated with
      distinct transcriptional status and are linked to distinct functional categories.
      CONCLUSIONS: We have designed and validated for the scientific community a
      comprehensive high-resolution tiling microarray for investigations of epigenetic
      states in zebrafish, a widely used developmental and disease model organism.

PMID- 21187972
TI  - Skeletal muscle myofibrillar and sarcoplasmic protein synthesis rates are
      affected differently by altitude-induced hypoxia in native lowlanders.
AB  - As a consequence to hypobaric hypoxic exposure skeletal muscle atrophy is often
      reported. The underlying mechanism has been suggested to involve a decrease in
      protein synthesis in order to conserve O(2). With the aim to challenge this
      hypothesis, we applied a primed, constant infusion of 1-(13)C-leucine in nine
      healthy male subjects at sea level and subsequently at high-altitude (4559 m)
      after 7-9 days of acclimatization. Physical activity levels and food and energy
      intake were controlled prior to the two experimental conditions with the aim to
      standardize these confounding factors. Blood samples and expired breath samples
      were collected hourly during the 4 hour trial and vastus lateralis muscle
      biopsies obtained at 1 and 4 hours after tracer priming in the overnight fasted
      state. Myofibrillar protein synthesis rate was doubled; 0.041+/-0.018 at sea
      level to 0.080+/-0.018%?hr(-1) (p<0.05) when acclimatized to high altitude. The
      sarcoplasmic protein synthesis rate was in contrast unaffected by altitude
      exposure; 0.052+/-0.019 at sea-level to 0.059+/-0.010%?hr(-1) (p>0.05). Trends to
      increments in whole body protein kinetics were seen: Degradation rate elevated
      from 2.51+/-0.21 at sea level to 2.73+/-0.13 umol?kg(-1)?min(-1) (p = 0.05) at
      high altitude and synthesis rate similar; 2.24+/-0.20 at sea level and 2.43+/
      0.13 umol?kg(-1)?min(-1) (p>0.05) at altitude. We conclude that whole body amino
      acid flux is increased due to an elevated protein turnover rate. Resting skeletal
      muscle myocontractile protein synthesis rate was concomitantly elevated by high
      altitude induced hypoxia, whereas the sarcoplasmic protein synthesis rate was
      unaffected by hypoxia. These changed responses may lead to divergent adaptation
      over the course of prolonged exposure.

PMID- 21187973
TI  - Markers of tumor-initiating cells predict chemoresistance in breast cancer.
AB  - PURPOSE: Evidence is lacking whether the number of breast tumor-initiating cells
      (BT-ICs) directly correlates with the sensitivity of breast tumors to
      chemotherapy. Here, we evaluated the association between proportion of BT-ICs and
      chemoresistance of the tumors. METHODS: Immunohistochemical staining(IHC) was
      used to examine the expression of aldehyde dehydrogenase 1 (ALDH1) and
      proliferating cell nuclear antigen, and TUNEL was used to detect the apoptosis
      index. The significance of various variables in patient survival was analyzed
      using a Cox proportional hazards model. The percentage of BT-ICs in breast cancer
      cell lines and primary breast tumors was determined by ALDH1 enzymatic assay,
      CD44(+)/CD24(-) phenotype and mammosphere formation assay. RESULTS: ALDH1
      expression determined by IHC in primary breast cancers was associated with poor
      clinical response to neoadjuvant chemotherapy and reduced survival in breast
      cancer patients. Breast tumors that contained higher proportion of BT-ICs with
      CD44(+)/CD24(-) phenotype, ALDH1 enzymatic activity and sphere forming capacity
      were more resistant to neoadjuvant chemotherapy. Chemoresistant cell lines
      AdrR/MCF-7 and SK-3rd, had increased number of cells with sphere forming
      capacity, CD44(+)/CD24(-) phenotype and side-population. Regardless the
      proportion of T-ICs, FACS-sorted CD44(+)/CD24(-) cells that derived from primary
      tumors or breast cancer lines were about 10-60 fold more resistant to
      chemotherapy relative to the non- CD44(+)/CD24(-) cells and their parental cells.
      Furthermore, our data demonstrated that MDR1 (multidrug resistance 1) and ABCG2
      (ATP-binding cassette sub-family G member 2) were upregulated in CD44(+)/CD24(-)
      cells. Treatment with lapatinib or salinomycin reduced the proportion of BT-ICs
      by nearly 50 fold, and thus enhanced the sensitivity of breast cancer cells to
      chemotherapy by around 30 fold. CONCLUSIONS: These data suggest that the
      proportion of BT-ICs is associated with chemotherapeutic resistance of breast
      cancer. It highlights the importance of targeting T-ICs, rather than eliminating
      the bulk of rapidly dividing and terminally differentiated cells, in novel anti
      cancer strategies.

PMID- 21187974
TI  - Inhibition of dehydration-induced water intake by glucocorticoids is associated
      with activation of hypothalamic natriuretic peptide receptor-A in rat.
AB  - Atrial natriuretic peptide (ANP) provides a potent defense mechanism against
      volume overload in mammals. Its primary receptor, natriuretic peptide receptor-A
      (NPR-A), is localized mostly in the kidney, but also is found in hypothalamic
      areas involved in body fluid volume regulation. Acute glucocorticoid
      administration produces potent diuresis and natriuresis, possibly by acting in
      the renal natriuretic peptide system. However, chronic glucocorticoid
      administration attenuates renal water and sodium excretion. The precise mechanism
      underlying this paradoxical phenomenon is unclear. We assume that chronic
      glucocorticoid administration may activate natriuretic peptide system in
      hypothalamus, and cause volume depletion by inhibiting dehydration-induced water
      intake. Volume depletion, in turn, compromises renal water excretion. To test
      this postulation, we determined the effect of dexamethasone on dehydration
      induced water intake and assessed the expression of NPR-A in the hypothalamus.
      The rats were deprived of water for 24 hours to have dehydrated status. Prior to
      free access to water, the water-deprived rats were pretreated with dexamethasone
      or vehicle. Urinary volume and water intake were monitored. We found that
      dexamethasone pretreatment not only produced potent diuresis, but dramatically
      inhibited the dehydration-induced water intake. Western blotting analysis showed
      the expression of NPR-A in the hypothalamus was dramatically upregulated by
      dexamethasone. Consequently, cyclic guanosine monophosphate (the second messenger
      for the ANP) content in the hypothalamus was remarkably increased. The inhibitory
      effect of dexamethasone on water intake presented in a time- and dose-dependent
      manner, which emerged at least after 18-hour dexamethasone pretreatment. This
      effect was glucocorticoid receptor (GR) mediated and was abolished by GR
      antagonist RU486. These results indicated a possible physiologic role for
      glucocorticoids in the hypothalamic control of water intake and revealed that the
      glucocorticoids can act centrally, as well as peripherally, to assist in the
      normalization of extracellular fluid volume.

PMID- 21187975
TI  - The nuclear inclusion a (NIa) protease of turnip mosaic virus (TuMV) cleaves
      amyloid-beta.
AB  - BACKGROUND: The nuclear inclusion a (NIa) protease of turnip mosaic virus (TuMV)
      is responsible for the processing of the viral polyprotein into functional
      proteins. NIa was previously shown to possess a relatively strict substrate
      specificity with a preference for Val-Xaa-His-Gln?, with the scissile bond
      located after Gln. The presence of the same consensus sequence, Val(12)-His-His
      Gln(15), near the presumptive alpha-secretase cleavage site of the amyloid-beta
      (Abeta) peptide led us to hypothesize that NIa could possess activity against
      Abeta. METHODOLOGY/PRINCIPAL FINDINGS: Western blotting results showed that
      oligomeric as well as monomeric forms of Abeta can be degraded by NIa in vitro.
      The specific cleavage of Abeta was further confirmed by mass spectrometry
      analysis. NIa was shown to exist predominantly in the cytoplasm as observed by
      immunofluorescence microscopy. The overexpression of NIa in B103 neuroblastoma
      cells resulted in a significant reduction in cell death caused by both
      intracellularly generated and exogenously added Abeta. Moreover, lentiviral
      mediated expression of NIa in APP(sw)/PS1 transgenic mice significantly reduced
      the levels of Abeta and plaques in the brain. CONCLUSIONS/SIGNIFICANCE: These
      results indicate that the degradation of Abeta in the cytoplasm could be a novel
      strategy to control the levels of Abeta, plaque formation, and the associated
      cell death.

PMID- 21187976
TI  - Differential contribution of rod and cone circadian clocks in driving retinal
      melatonin rhythms in Xenopus.
AB  - BACKGROUND: Although an endogenous circadian clock located in the retinal
      photoreceptor layer governs various physiological events including melatonin
      rhythms in Xenopus laevis, it remains unknown which of the photoreceptors, rod
      and/or cone, is responsible for the circadian regulation of melatonin release.
      METHODOLOGY/PRINCIPAL FINDINGS: We selectively disrupted circadian clock function
      in either the rod or cone photoreceptor cells by generating transgenic Xenopus
      tadpoles expressing a dominant-negative CLOCK (XCLDeltaQ) under the control of a
      rod or cone-specific promoter. Eyecup culture and continuous melatonin
      measurement revealed that circadian rhythms of melatonin release were abolished
      in a majority of the rod-specific XCLDeltaQ transgenic tadpoles, although the
      percentage of arrhythmia was lower than that of transgenic tadpole eyes
      expressing XCLDeltaQ in both rods and cones. In contrast, whereas a higher
      percentage of arrhythmia was observed in the eyes of the cone-specific XCLDeltaQ
      transgenic tadpoles compare to wild-type counterparts, the rate was significantly
      lower than in rod-specific transgenics. The levels of the transgene expression
      were comparable between these two different types of transgenics. In addition,
      the average overall melatonin levels were not changed in the arrhythmic eyes,
      suggesting that CLOCK does not affect absolute levels of melatonin, only its
      temporal expression pattern. CONCLUSIONS/SIGNIFICANCE: These results suggest that
      although the Xenopus retina is made up of approximately equal numbers of rods and
      cones, the circadian clocks in the rod cells play a dominant role in driving
      circadian melatonin rhythmicity in the Xenopus retina, although some contribution
      of the clock in cone cells cannot be excluded.

PMID- 21187977
TI  - Insertion sequence inversions mediated by ectopic recombination between terminal
      inverted repeats.
AB  - Transposable elements are widely distributed and diverse in both eukaryotes and
      prokaryotes, as exemplified by DNA transposons. As a result, they represent a
      considerable source of genomic variation, for example through ectopic (i.e. non
      allelic homologous) recombination events between transposable element copies,
      resulting in genomic rearrangements. Ectopic recombination may also take place
      between homologous sequences located within transposable element sequences. DNA
      transposons are typically bounded by terminal inverted repeats (TIRs). Ectopic
      recombination between TIRs is expected to result in DNA transposon inversions.
      However, such inversions have barely been documented. In this study, we report
      natural inversions of the most common prokaryotic DNA transposons: insertion
      sequences (IS). We identified natural TIR-TIR recombination-mediated inversions
      in 9% of IS insertion loci investigated in Wolbachia bacteria, which suggests
      that recombination between IS TIRs may be a quite common, albeit largely
      overlooked, source of genomic diversity in bacteria. We suggest that inversions
      may impede IS survival and proliferation in the host genome by altering
      transpositional activity. They may also alter genomic instability by modulating
      the outcome of ectopic recombination events between IS copies in various
      orientations. This study represents the first report of TIR-TIR recombination
      within bacterial IS elements and it thereby uncovers a novel mechanism of
      structural variation for this class of prokaryotic transposable elements.

PMID- 21187978
TI  - Synaptic neurotransmission depression in ventral tegmental dopamine neurons and
      cannabinoid-associated addictive learning.
AB  - Drug addiction is an association of compulsive drug use with long-term
      associative learning/memory. Multiple forms of learning/memory are primarily
      subserved by activity- or experience-dependent synaptic long-term potentiation
      (LTP) and long-term depression (LTD). Recent studies suggest LTP expression in
      locally activated glutamate synapses onto dopamine neurons (local Glu-DA
      synapses) of the midbrain ventral tegmental area (VTA) following a single or
      chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid
      did not significantly affect synaptic plasticity at these synapses. It is unknown
      whether chronic exposure of cannabis (marijuana or cannabinoids), the most
      commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More
      importantly, whether such alterations in VTA synaptic plasticity causatively
      contribute to drug addictive behavior has not previously been addressed. Here we
      show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1
      receptors to induce transient neurotransmission depression at VTA local Glu-DA
      synapses through activation of NMDA receptors and subsequent endocytosis of AMPA
      receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA
      synaptic depression and conditioned place preference, i.e., learning to associate
      drug exposure with environmental cues. These data not only provide the first
      evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at
      VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential
      contribution of such synaptic depression to cannabinoid-associated addictive
      learning, in addition to pointing to novel pharmacological strategies for the
      treatment of cannabis addiction.

PMID- 21187980
TI  - Light weight meshes in incisional hernia repair.
AB  - Incisional hernias remain one of the most common surgical complications with a
      long-term incidence of 10-20%. Increasing evidence of impaired wound healing in
      these patients supports routine use of an open prefascial, retromuscular mesh
      repair. Basic pathophysiologic principles dictate that for a successful long-term
      outcome and prevention of recurrence, a wide overlap underneath healthy tissue is
      required. Particularly in the neighborhood of osseous structures, only
      retromuscular placement allows sufficient subduction of the mesh by healthy
      tissue of at least 5 cm in all directions. Preparation must take into account the
      special anatomic features of the abdominal wall, especially in the area of the
      Linea alba and Linea semilunaris. Polypropylene is the material widely used for
      open mesh repair. New developments have led to low-weight, large-pore
      polypropylene prostheses, which are adjusted to the physiological requirements of
      the abdominal wall and permit proper tissue integration. These meshes provide the
      possibility of forming a scar net instead of a stiff scar plate and therefore
      help to avoid former known mesh complications.

PMID- 21187981
TI  - The Shouldice technique for the treatment of inguinal hernia.
AB  - The Shouldice repair has been refined over several decades and is the gold
      standard for the prosthesisfree treatment of inguinal hernias. A recurrence rate
      around 1% has been consistently demonstrated over the years. The objective of
      this paper is to outline and highlight the key principles, including the
      dedicated pre-operative preparation, the use of local anesthesia, a complete
      inguinal dissection and the eponymous four-layered reconstruction. A knowledge
      and understanding of inguinal hernia anatomy and the patho-physiology of
      recurrence are vital to achieving a long-term success and patient satisfaction
      for a pure tissue repair.

PMID- 21187982
TI  - A modified Lichtenstein hernia repair using fibrin glue.
AB  - In recent years, general surgeons who perform inguinal hernia repair have paid
      attention to successful reduction in the recurrence rate. The Lichtenstein
      technique is widely used because it is easy to learn and is associated with a low
      rate of complication and recurrences. Today, the new objective in primary hernia
      surgery should be to reduce complications such as chronic pain. Chronic pain
      after hernia repair can be disabling, with considerable impact on quality of life
      and there is evidence to suggest increased use of health services by patients who
      have chronic pain. We have proposed an international randomized controlled trial
      with seven referenced European centers: The TI.ME.LI. trial. The aim of this
      study is to evaluate pain and further disabling complications in patients
      undergoing Lichtenstein technique for primary inguinal hernia repair by fixing
      the mesh with fibrin sealant versus sutures (control group).

PMID- 21187979
TI  - Olfactory stem cells, a new cellular model for studying molecular mechanisms
      underlying familial dysautonomia.
AB  - BACKGROUND: Familial dysautonomia (FD) is a hereditary neuropathy caused by
      mutations in the IKBKAP gene, the most common of which results in variable tissue
      specific mRNA splicing with skipping of exon 20. Defective splicing is especially
      severe in nervous tissue, leading to incomplete development and progressive
      degeneration of sensory and autonomic neurons. The specificity of neuron loss in
      FD is poorly understood due to the lack of an appropriate model system. To better
      understand and modelize the molecular mechanisms of IKBKAP mRNA splicing, we
      collected human olfactory ecto-mesenchymal stem cells (hOE-MSC) from FD patients.
      hOE-MSCs have a pluripotent ability to differentiate into various cell lineages,
      including neurons and glial cells. METHODOLOGY/PRINCIPAL FINDINGS: We confirmed
      IKBKAP mRNA alternative splicing in FD hOE-MSCs and identified 2 novel spliced
      isoforms also present in control cells. We observed a significant lower
      expression of both IKBKAP transcript and IKAP/hELP1 protein in FD cells resulting
      from the degradation of the transcript isoform skipping exon 20. We localized
      IKAP/hELP1 in different cell compartments, including the nucleus, which supports
      multiple roles for that protein. We also investigated cellular pathways altered
      in FD, at the genome-wide level, and confirmed that cell migration and
      cytoskeleton reorganization were among the processes altered in FD. Indeed, FD
      hOE-MSCs exhibit impaired migration compared to control cells. Moreover, we
      showed that kinetin improved exon 20 inclusion and restores a normal level of
      IKAP/hELP1 in FD hOE-MSCs. Furthermore, we were able to modify the IKBKAP
      splicing ratio in FD hOE-MSCs, increasing or reducing the WT (exon 20
      inclusion):MU (exon 20 skipping) ratio respectively, either by producing free
      floating spheres, or by inducing cells into neural differentiation.
      CONCLUSIONS/SIGNIFICANCE: hOE-MSCs isolated from FD patients represent a new
      approach for modeling FD to better understand genetic expression and possible
      therapeutic approaches. This model could also be applied to other neurological
      genetic diseases.

PMID- 21187983
TI  - Cure of inguinal hernias with large preperitoneal prosthesis: Experience of 2,312
      cases.
AB  - It is clear that the recurrence rates after nonprosthetic methods for the repair
      of inguinal hernias, like McVay, Bassini or Shouldice techniques, are high (6
      10%). Since 20 years, we are convinced, in the GREPA-EHS group, about the
      advantages of the use of a prosthetic mesh in majority of patients for repairs of
      primary or recurrent inguinal hernias and incisional hernias. We describe our
      typical technique for the cure of all inguinal hernias. We place a large supple
      mesh, by open inguinal route, posterior to the transversalis fascia and anterior
      to the peritoneum. We have made a double modification in the initial technique of
      Rives - the use of a very large unsplit prosthesis (15 * 17 cm) and the
      parietalization of the spermatic cord helped by a wide opening of the Fruchaud's
      orifice by diversion of the epigastric vessels. The positioning of the mesh is
      about the same as in the TEP technique but with the advantages of reduction in
      the vital laparoscopic risks and reinforcement of the wall by a short tension
      free McVay technique.For this prospective study, we repaired 2,312 consecutive
      hernias in 1,828 patients, 284 of which were recurrent. We present our results in
      terms of quality of repairs, recurrence rates (0.4%), morbidity rate (8%), and
      mortality rate (0.8%).This technique involves the placement by an open incisional
      route of a large preperitoneal sheet of mesh for initial treatment of all
      inguinal hernias - including scrotal, giant or femoral - to ensure a definitive
      solid muscular wall, even for recurrent hernias.

PMID- 21187984
TI  - Tension free open inguinal hernia repair using an innovative self gripping semi
      resorbable mesh.
AB  - AIMS: Inguinal hernia repair according to Lichtenstein technique has become the
      most common procedure performed by general surgeons. Heavy weight polypropylene
      meshes have been reported to stimulate inflammatory reaction responsible for mesh
      shrinkage when scar tissue evolved. Additionally, some concerns remain regarding
      the relationship between chronic pain and mesh fixation technique. In order to
      reduce those drawbacks, we have developed a new mesh for anterior tension free
      inguinal hernia repair which exhibits self-gripping absorbable properties.
      MATERIALS AND METHODS: 52 patients (69 hernias) were prospectivly operated with
      this mesh (SOFRADIM-France) made of low-weight isoelastic large pores knitted
      fabric which incorporated resorbable micro hooks that provides self gripping
      properties to the mesh during the first months post-implantation. The fixation of
      the mesh onto the tissues is significantly facilitated. The mesh is secured
      around the cord with a self gripping flap. After complete tissular ingrowth and
      resorption of the PLA hooks, the low-weight (40 g/m(2)) polypropylene mesh
      insures the long term wall reinforcement. RESULTS: Peroperativly, no complication
      was reported, the mesh was easy to handle and to fix. Discharge was obtained at
      Day 1. No perioperative complication occurred, return to daily activities was
      obtained at Day 5.5. At one month, no neurological pain or other complications
      were described. CONCLUSIONS: Based on the first results of this clinical study,
      this unique concept of low density self gripping mesh should allows an efficient
      treatment of inguinal hernia. It should reduce postoperative complications and
      the extent of required suture fixation, making the procedure more reproducible.

PMID- 21187985
TI  - Inguinal hernia repair: The total picture.

PMID- 21187986
TI  - Inguinal hernia recurrence: Classification and approach.
AB  - The authors reviewed the records of 2,468 operations of groin hernia in 2,350
      patients, including 277 recurrent hernias updated to January 2005. The data
      obtained - evaluating technique, results and complications - were used to propose
      a simple anatomo-clinical classification into three types which could be used to
      plan the surgical strategy: Type R1: first recurrence 'high,' oblique external,
      reducible hernia with small (<2 cm) defect in non-obese patients, after pure
      tissue or mesh repairType R2: first recurrence 'low,' direct, reducible hernia
      with small (<2 cm) defect in non-obese patients, after pure tissue or mesh
      repairType R3: all the other recurrences - including femoral recurrences;
      recurrent groin hernia with big defect (inguinal eventration); multirecurrent
      hernias; nonreducible, linked with a controlateral primitive or recurrent hernia;
      and situations compromised from aggravating factors (for example obesity) or
      anyway not easily included in R1 or R2, after pure tissue or mesh repair.

PMID- 21187987
TI  - Hernia recurrence as a problem of biology and collagen.
AB  - Usually an abdominal wall hernia is regarded as a mechanical problem with a local
      defect which has to be closed by technical means. Despite the introduction of
      several therapeutic improvements, recurrent hernias still appear in 10-15%.
      Therefore, reasons for a recurrence are discussed in a more fundamental way. It
      is assumed that a failure mainly depends on the quality of the repair.
      Correspondingly, in principle, the close causal relationship between the
      technical component and its failure during time is reflected by an s-shaped
      outcome curve. In contrast, the configuration of the outcome curve changes
      markedly if a breakdown is caused by numerous components. Then, the superposition
      of all incidence curves inevitably leads to a linear decline of the outcome curve
      without any s-shaped deformation. Regarding outcome curves after hernia repair,
      the cumulative incidences for recurrences of both incisional and inguinal hernia
      show a linear rise over years. Considering the configuration of outcome curves of
      patients with hernia disease, it may therefore be insufficient to explain a
      recurrence just by a failing technical repair. Rather, biological reasons should
      be suspected, such as a defective wound healing with impaired scarring process.
      Recent molecular-biological findings provide increasing evidence of underlying
      biochemical alterations in patients with recurrent hernia. Until predicting
      markers to identify patients with an impaired wound healing are available and
      considering the formation of insufficient scar as the underlying disease, the
      consequences for every surgical repair should be a supplementary reinforcement
      with nonabsorbable alloplastic nets as flat meshes with an extensive overlap.

PMID- 21187988
TI  - TAPP - Stuttgart technique and result of a large single center series.
AB  - Laparoscopic hernioplasty is assessed as a difficult operation. Operative
      technique determines the frequency of complications, the time of recovery and the
      rate of recurrences. A proper technique is absolutely necessary to achieve
      results that are superior to open hernia surgery. TECHNIQUE: The key points in
      our technique are 1) use of nondisposable instruments; 2) use of blunt trocars,
      consisting of expanding and non-incisive cone-shaped tips; 3) spacious and curved
      opening to the peritoneum, high above all possible hernia openings; 4) meticulous
      dissection of the entire pelvic floor; 5) complete reduction of the hernial sac;
      6) wide parietalization of the peritoneal sac, at least down to the mid of psoas
      muscle; 7) implantation of a large mesh, at least 10 cm * 15 cm; 8) fixation of
      the mesh by clip to Cooper's ligament, to the rectus muscle and lateral to the
      epigastric vessels, high above the ileopubic tract; 9) the use of glue allows
      fixation also to the latero-caudial region; and 10) closure of the peritoneum by
      running suture. RESULTS: With this technique in 12,678 hernia repairs, the
      following results could be achieved: operating time - 40 min; morbidity - 2.9%;
      recurrence rate - 0.7%; disability of work - 14 days. In all types of hernias
      (recurrence after previous open surgery, recurrence after previous preperitoneal
      operation, scrotal hernia, hernia in patients after transabdominal prostate
      resection), similar results could be achieved. SUMMARY: Laparoscopic hernia
      repair can be performed successfully in clinical practice even by surgeons in
      training. Precondition for the success is a strictly standardized operative
      technique and a well-structured educational program.

PMID- 21187989
TI  - Totally extraperitoneal repair of inguinal hernia: Sir Ganga Ram Hospital
      technique.
AB  - Laparoscopic approach for hernia has evolved rapidly over the past decade. We
      adopted the TEP repair early as we believe in preserving the sanctity of the
      coelomic cavity. Once well versed with the approach we have found it an efficient
      and cost effective method for groin hernia repair.Endoscopic totally
      extraperitoneal hernia repair is a technically demanding procedure. Indepth
      anatomical knowledge, training and advanced technical skill is needed for the
      surgeon to perform this procedure. To make the procedure cost effective and
      prevent hernia recurrences, we have modified and innovated to simplify the
      procedure.This modification which we have named the SGRH technique, innovates by
      creating the preperitoneal working space with the help of an indigenous glove
      finger balloon. A rolled mesh makes placement and fixation easier in the limited
      working space. The mesh is unrolled on the peritoneal surface (floor), a manouver
      which is technically simpler. On desufflation the mesh comes to appose the
      Fruchad's orifice covering all potential hernial sites. With the modified SGRH
      technique we have found TEP to be safe, cost effective, reproducible and without
      significant complications.

PMID- 21187990
TI  - Managing intra-operative complications during totally extraperitoneal repair of
      inguinal hernia.
AB  - Laparoscopic inguinal hernia repairs are looked upon as technically demanding
      procedures having have a stiff 'learning curve' associated with its performance
      in terms of clinical outcome and patient's satisfaction. Complication rates have
      been shown to drop with increased surgical experience. The complication rate for
      laparoscopic repair of inguinal hernia ranges from less than 3% to as high as
      20%. Complications of a totally extraperitoneal (TEP) repair include general
      complications that occur with any surgical procedure and anesthesia, mesh-related
      complications and those specific to the TEP procedure, like visceral injury,
      vascular injury, nerve injury and injury to the cord. Intraoperative
      complications can occur at every step of the operation, even though some of them
      are only occasionally reported. However, it is important to analyze all of them
      chronologically, so that we can define methods to prevent them or tackle them if
      they occur. Risk reduction strategies are required to improve the clinical
      outcome of TEP and this must be adopted for each individual surgical step.

PMID- 21187991
TI  - Totally extraperitoneal repair of inguinal hernia: A case for bilateral repair.
AB  - Inguinal hernia surgery has been one of the most extensively debated and
      continues to evolve in search for the ideal technique. Even though the method to
      diagnose hernia has largely remained clinical, recently other modalities have
      detected hernias that are not picked up on clinical examination or are
      incorrectly labeled. Laparoscopy, for the first time has given surgeons the
      unique opportunity to look at both sides of the groin and to detect and study the
      contra lateral groin in a patient of clinically unilateral hernia. This has given
      rise to some interesting findings. In the pediatric age group the value of
      bilateral detection and repair has been extensively debated. However, the same is
      not true for the adults despite the facts that there are better methods for
      detection, better understanding of pathogenesis of hernia and better repair
      techniques that can take care of bilateral repair without adding to
      morbidity.That hernia is not a simple derivative of patent processus vaginalis or
      strain related cause is beginning to be better understood now. It may primarily
      be a disorder of collagen metabolism with genetic basis. Laparoscopy has also
      made us wiser in detection of type of hernia and examination of both groin areas.
      In several studies there have been a high percentage of undetected hernias or
      additional defects. This was never realized earlier as in open surgery there is
      no question of exploring the asymptomatic groin. Laparoscopy in bilateral repair
      is safe and does not add significantly to the operating time, cost or
      morbidity.At our Department of Minimal Access Surgery, Sir Ganga Ram Hospital,
      New Delhi, India we have been performing Endoscopic Totally Extraperitoneal (TEP)
      repair for all simple and complicated inguinal hernia since 1994. We now
      routinely perform a bilateral repair based on our understanding that the
      pathogenesis of hernia is a complex process and any genetic basis of collagen
      disorder has to affect the patient bilaterally. The clinical examination may have
      unacceptably low sensitivity. Early identification and repair obviates the need
      for reoperation, reduces overall costs and eliminates further anaesthetic and
      operative risks for the patient.

PMID- 21187992
TI  - Complications in groin hernia surgery and the way out.
AB  - Complications in endoscopic inguinal hernia surgery are more dangerous and more
      frequent than those of open surgery, especially in inexperienced hands and hence
      are best avoided. It is possible to avoid most of these complications if one
      follows a set of well-defined steps and principles of endoscopic inguinal hernia
      surgery.Complications are known to occur at each and every step of hernia
      surgery. Applying caution while performing each step can save the patient from a
      lot of morbidity. One starts by applying strict patient selection criteria for
      endoscopic hernia repair, especially in the initial part of ones learning curve.
      A thorough knowledge of anatomy goes a long way in avoiding most of the
      complications seen in hernia repair. This anatomy needs to be relearned from what
      one is used to, as the approach is totally different from an open hernia repair.
      And finally, learning and mastering the right technique is an essential
      prerequisite before one ventures into inguinal hernia repair.Although there has
      been an increased incidence of complications reported in endoscopic repair in the
      earlier series, this can be explained partly by the fact that it was in the early
      part of the learning curve of most endoscopic surgeons. As the experience grew
      and the techniques were standardized, the incidences of complications have also
      reduced and have come to be on par with open hernia surgery. The various
      complications and precautions to be taken to avoid them will be discussed.

PMID- 21187993
TI  - Laparoscopic surgery for inguinal hernia: Current status and controversies.
AB  - Repair of inguinal hernia is one of the commonest operations performed by
      surgeons around the world. The treatment of this common problem has seen an
      evolution from the pure tissue repairs to the prosthetic repairs and in the
      recent past to laparoscopic repair. The fact that so many hernia repairs are
      practiced is a testimony to the fact that probably none is distinctly superior to
      the other. This review assesses the current status of surgery for repair of
      inguinal hernia and examines the various controversial issues surrounding the
      subject.

PMID- 21187994
TI  - Causes of recurrence in laparoscopic inguinal hernia repair.
AB  - AIM: The analysis of possible mechanisms of repair failure is a necessary
      instrument and the best way to decrease the recurrence rate and improve the
      overall results. Avoiding historical errors and learning from the reported
      pitfalls and mistakes helps to standardize the relatively new laparoscopic
      techniques of trans-abdominal preperitoneal and total extraperitoneal. MATERIALS
      AND METHODS: The video tapes of all primary laparoscopic repairs done by the
      author that led to recurrence were retrospectively analyzed and compared with
      findings at the second laparoscopic repair. A review of the available cases of
      recurrences occurring between 1994 and 2003 is the basis of this report. SUMMARY:
      Adequate mesh size, porosity of mesh material, slitting of the mesh, correct and
      generous dissection of preperitoneal space and wrinkle-free placement of the mesh
      seem to be the more important factors in avoiding recurrence rather than strength
      of the material or strong penetrating fixation. Special attention should be paid
      to preperitoneal lipoma as a possible overlooked herniation or potential future
      pseudorecurrence despite nondislocated correctly positioned mesh. CONCLUSION:
      Laparoscopic hernia repair is a complex but very efficient method in experienced
      hands. To achieve the best possible results, it requires an acceptance of a
      longer learning curve, structured well-mentored training and high level of
      standardization of the operative procedure.

PMID- 21187995
TI  - Laparoscopic repair of ventral / incisional hernias.
AB  - Despite its significant prevalence, there is little in the way of evidence-based
      guidelines regarding the timing and method of repair of incisional hernias. To
      add to the above is the formidable rate of recurrence that has been seen with
      conventional tissue repairs of these hernias. With introduction of different
      prosthetic materials and laparoscopic technique, it was hoped that an improvement
      in the recurrence and complication rates would be realized. The increasing
      application of the laparoscopic technique across the world indicates that these
      goals might indeed be achieved.

PMID- 21187996
TI  - Mechanical valve dysfunction in yemen.
AB  - BACKGROUND: Rheumatic heart disease is the most common cardiac disease in Yemen.
      It is associated with high morbidity and mortality. Valve replacement is the most
      common open heart surgery procedure in our cardiac center. The use of mechanical
      valves remains burdened with serious complications such as thrombosis. Valve
      thrombosis is still associated with high mortality(]) The reported mortality rate
      of the redo operation ranges from 8 to 20% and up to 37-54% in critically ill
      patients. OBJECTIVE: The aim of the present study was to investigate mechanical
      valve obstruction among Yemeni patients. PATIENTS AND METHODS: Between January
      2003 and April 2007, 2794 patients underwent prosthetic valve replacement in our
      center, Al-Thawra Hospital. Of those patients, 129 (4.6%) underwent reoperation
      for te obstructive mechanical valve. Patients with clinical suspicion of
      prosthetic valve obstruction (PVO) were admitted emergently to the CCU and the
      diagnosis was confirmed with echocardiography. All patients had heart failure;
      95% of them were in NYHA class IV. All were transferred directly from the CCU to
      the operating room. The mean age was 34.8 +/- 13.4 years. Two patients received
      preoperative thrombolytic therapy that was not successful. Obstruction involved
      the mitral valve prosthesis in 47 (36.4%); the aortic prosthesis in 16 (12.4%)
      patients; both valves in 21 (16.3%) patients; mitral valve replacement with
      tricuspid valve repair in 22(17%); double valve replacement with tricuspid valve
      repair in 1 (0.8%); redo mitral valve replacement with aortic valve cleaning in 7
      (5.4%) cases; aortic valve cleaning in 5 (3.9%) patients; mitral valve cleaning
      in 5 (3.9%); and 5 (3.9%) patients had redo mitral with aortic replacement.
      RESULTS: The operations were performed urgently. The etiology of the obstruction
      was thrombus in 111 (86%), pannus formation in 4 (3%), pannus and thrombus in 6
      (4.8%), vegetation in 7 (5.4%) patients, and interposition of suturing materials
      in 1 (0.8%) patient. The in- hospital mortality was 23/129 (17.8%). CONCLUSION:
      The incidence of prosthetic valve obstruction remains high in Yemen. The vast
      majority of the patients who are referred to our hospital come from remote
      provinces in the country where regular INR measurement is not readily available.
      For those who are living in areas without good medical care, certain measures are
      necessary to avoid this disastrous complication: (1) good patient education, (2)
      free INR testing and free anticoagulant drugs such as warfarin; and (3) use of
      tissue rather than mechanical valves.

PMID- 21187997
TI  - Protocol-Guided Phase-1 Cardiac Rehabilitation in Patients with ST-Elevation
      Myocardial Infarction in A Rural Hospital.
AB  - AIMS: Phase-1 Cardiac Rehabilitation (CR) is an important part in the treatment
      of patients with ST-Elevation Myocardial Infarction (STEMI). Lack of literature
      in the rural Indian setting led to the design of this study. SETTING AND DESIGN:
      Secondary care rural hospital, non-randomized experimental study. MATERIALS AND
      METHODS: Fifteen historical controls and 15 prospectively enrolled patients
      between January 2007 and December 2007. The prospectively enrolled patients
      received the phase-1, exercise-based, protocol-guided CR. At discharge, the six
      minute walk test (6MWT) distance, Borg's Rating of Perceived Exertion (RPE) after
      the 6MWT, time to return to baseline parameters after the 6MWT, and complications
      were assessed. STATISTICAL ANALYSIS USED: Independent t-test and the Mann Whitney
      test. RESULTS: Statistically significant (P < 0.01) differences in ratings of
      perceived exertion (RPE) and time to return to baseline parameters post the 6MWT
      were seen in the experimental group ((2 vs. 4 and 5.47 vs. 7.93 minutes,
      respectively). No significant changes in the 6MWT distance between the groups
      were noticed (470+/-151.76 m and 379+/-170.70 m, respectively). No adverse events
      during the 6MWT and the phase-1 CR were observed. CONCLUSION: Protocol-guided,
      phase-1 CR produces a much faster return of heart rate and blood pressure to
      baseline following the 6MWT, without producing a great rise in the RPE during the
      6MWT, which suggests a training benefit among these patients. The 6MWT can be
      safely administered in this rural population. However, larger studies will be
      required to validate these results.

PMID- 21187998
TI  - Atrial fibrillation post cardiac surgery trends toward management.
AB  - Post operative atrial fibrillation (POAF) is more common than before due to
      increased numbers of cardiac surgeries. This in turn is associated with increased
      incidence of post operative complication, length of hospital stay and subsequent
      increase the cost of hospitalization. Therefore preventing and/or minimizing
      atrial fibrillation by pharmacological or nonpharmacological means is a
      reasonable goal. POAF has also been associated with postoperative delirium and
      neurocognitive decline. The precise pathophysiology of POAF is unknown, however
      most of the evidence suggests it is multifactorial. Different risk factors have
      been reported, and many studies have evaluated the prophylactic effects of
      different interventions. This review article highlights the incidence, risk
      factors, and pathogenesis, prevention, and treatment strategies of POAF.

PMID- 21187999
TI  - Type IV Dual Left Anterior Descending Coronary Artery:A Rare Anomaly.
AB  - Type IV dual left anterior descending (LAD) coronary artery is a rare anomaly and
      was detected incidentally during a routine coronary angiogram. The article
      discusses the types of dual LAD and their clinical implications.

PMID- 21188000
TI  - Dual left anterior descending coronary artery.

PMID- 21188001
TI  - Acute intracoronary thrombosis in a normal coronary artery following coronary
      angiography: thromboaspiration using a guide catheter.
AB  - A 60-year-old female presented with anterolateral non-ST elevation myocardial
      infarction and her coronary angiogram revealed severe left system coronary artery
      disease with a normal right coronary artery. Following coronary angiogram, she
      developed acute inferior wall and right ventricular ST elevation myocardial
      infarction with complete atrioventricular block and cardiogenic shock. Repeat
      coronary angiogram showed large proximal right coronary thrombus causing subtotal
      occlusion that was successfully aspirated using a guide catheter. The possible
      causes for intracoronary thrombosis following coronary angiography are discussed
      here.

PMID- 21188002
TI  - "MacCallum Plaque of the Heart": A Medicolegal Case.
AB  - Mural endocardial lesions can be seen as MacCallum plaques in rheumatic heart
      disease. These plaques appear as map-like areas of thickened, roughened, and
      wrinkled part of the endocardium in the left atrium. Perhaps they are caused by
      regurgitant jets of blood flow, due to incompetence of the mitral valve. Although
      MacCallum plaques are one of the characteristic features in rheumatic heart
      disease, they are very uncommon in recent times. We hereby report a case of an
      adolescent female with RHD, who was working as a housemaid in a doctor's house
      for a few months, and suddenly developed respiratory tract infection and cardiac
      failure. She died on the fourth day of admission. A medicolegal autopsy was
      conducted, as her relatives accused her master of sexual assault. On autopsy it
      was seen that the mitral valves were narrowed, showing multiple vegetations.
      MacCallum plaque was seen in the dilated left atrium. Hence, it is presented here
      for educative purposes.

PMID- 21188003
TI  - Echocardiography in left ventricular assist device.
AB  - LVAD = Left Ventricular Assist Device; LV = Left Ventricle; LA = Left Atrium; AO
      = Aorta.

PMID- 21188004
TI  - Scene in an open-air pharmacy.

PMID- 21188005
TI  - The magnificent century of cardiothoracic surgery part 8: reviving the dead.

PMID- 21188006
TI  - Laparoscopic liver resections.
AB  - THOUGH STILL PRACTICED IN ONLY A FEW CENTRES WORLDWIDE, LAPAROSCOPIC LIVER
      RESECTIONS, PARTICULARLY LEFT HEPATECTOMY OFFER ADVANTAGES OVER THE CONVENTIONAL
      OPEN APPROACH IN TWO IMPORTANT RESPECTS: reduced operative blood loss and lower
      major postoperative morbidity. Two approaches are used: the totally laparoscopic
      and the hand-assisted technique, which in the author's opinion facilitates both
      the execution and safety of these procedures, especially major resection of the
      right liver (right hepatectomy and pluri-segmentectomies). Technologies, which
      have enabled hepatic resections include: laparoscopic contact ultrasound, linear
      cutting staplers, ultrasonic dissection, LigaSure and TissueLink. The components
      operative steps necessary for these resections as practised by the author are
      described in this review.

PMID- 21188007
TI  - Hand-assisted laparoscopic surgery using Gelport.
AB  - INTRODUCTION: Minimally invasive surgery has revolutionized general surgery
      during the past 10 years. However, for more advanced surgical procedures, the
      acceptance of the minimally invasive approach has been slower than expected.
      Advanced laparoscopic surgery is complex and time-consuming. The major drawbacks
      of laparoscopic surgery are two-dimensional view, lack of depth perception and
      loss of tactile sensation. This has led to the innovation of hand-assisted
      laparoscopic surgery (HALS). The objective of the present study was to determine
      that safety of HALS. MATERIALS AND METHODS: We preformed 18 HALS procedures in
      our department between July 2003 and January 2005 on patients who had given their
      informed consent for the use of Gelport. Out of these, 15 were colectomy, 2
      nephrectomy and 1 splenectomy. Out of the 18 patients, 13 were males and 5 were
      females with the age group ranging from 44 to 72 years. RESULTS: Hand-assisted
      laparoscopic surgery could be completed in 17 patients maintaining all the
      oncological principals of surgery. The mean operating times were 120 min for
      right haemicolectomy, 135 min for left colectomy, 150 min for splenectomy, and
      150 min for nephrectomy. The patient undergoing radical nephrectomy by HALS had
      to be converted to open surgery. As the tumour was large and adherent to the
      spleen and posterior peritoneal wall. Postoperative recovery was excellent with
      an average hospital stay of 5 days. Histopathology report showed wide clearance
      and till date we have a good follow up of 30-380 days. CONCLUSION: Hand-assisted
      laparoscopic surgery allows tactile sensation and depth perception thereby may
      simplify the complex procedures. This may result in reduction of operating time
      and conversion rates at the same time maintaining all the oncological principles.
      Hand-assisted laparoscopic surgery strikes a perfect balance between an extended
      open laparotomy incision and an excessively tedious laparoscopic exercise. Hand
      assistance is an initial tool for the trainee laparoscopic surgeon or a last
      resort for the experienced laparoscopic surgeon.

PMID- 21188008
TI  - Role of laparoscopy in evaluation of chronic pelvic pain.
AB  - INTRODUCTION: Chronic pelvic pain (CPP) is a common medical problem affecting
      women. Too often the physical signs are not specific. This study aims at
      determining the accuracy of diagnostic laparoscopy over clinical pelvic
      examination. SETTINGS AND DESIGN: A retrospective study of patients who underwent
      diagnostic laparoscopy for CPP. MATERIALS AND METHODS: The medical records of 86
      women who underwent laparoscopic evaluation for CPP of at least 6-month duration
      were reviewed for presentation of symptoms, pelvic examination findings at the
      admission, operative findings and follow up when available. STATISTICAL ANALYSIS
      USED: McNemar Chi-square test for frequencies in a 2 * 2 table. RESULTS: The most
      common presentation was acyclic lower abdominal pain (79.1%), followed by
      congestive dysmenorrhoea (26.7%). 61.6% of women did not reveal any significant
      signs on pelvic examination. Pelvic tenderness was elicited in 27.9%. Diagnostic
      laparoscopy revealed significant pelvic pathology in 58% of those who essentially
      had normal pervaginal findings. The most common pelvic pathology by laparoscopy
      was pelvic adhesions (20.9%), followed by pelvic congestion (18.6%). Laparoscopic
      adhesiolyis achieved pain relief only in one-third of the women. CONCLUSION: The
      study revealed very low incidence of endometriosis (4.7%). Overall clinical
      examination could detect abnormality in only 38% of women, where as laparoscopy
      could detect significant pathology in 66% of women with CPP. This shows
      superiority of diagnostic laparoscopy over clinical examination in detection of
      aetiology in women with CPP (P < 0.001). Adhesiolysis helps only small proportion
      of women in achieving pain control.

PMID- 21188009
TI  - Minimal access surgery in children - 5 years institutional experience.
AB  - CONTEXT: Minimal access surgery (MAS) in children are common place and performed
      worldwide with gratifying results as the learning curve of the surgeon attains
      plateau. We share our experience of this technically evolving modality of
      surgery, performed at our setup over a period of 5 years. We also review and
      individually compare the data for commonly performed procedures with other
      available series. Author also briefly discuss potential advantages of MAS in
      certain debatable conditions performed quickly and with cosmesis as open
      procedure. MATERIALS AND METHODS: We performed 677 MAS in children aged between 7
      days and 12 years. Five hundred and sixty-eight of these were Laparoscopic
      procedures and 109 were Video assisted thoracoscopic surgeries (VATS). In all
      laparoscopic procedures, the primary port placement was by the Hasson's open
      technique. We have used 5, 3 and 2 mm instruments. Our study include 259 inguinal
      hernia, 161 Appendectomies, 95 VATS for empyema, 51 orchiopexies, 49 diagnostic
      laparoscopy, 29 cholecystectomies, 22 adhesionlysis and other uncommonly
      performed procedures. RESULTS: The ultimate outcome of all the performed
      procedures showed gratifying trend, the data of which are discussed in detail in
      the article. CONCLUSION: As we gained experience the operating time showed a
      decreasing trend, the complication rates and conversion rate also reduced. The
      advantages we came across were better postoperative appearances, less pain and
      early return to unrestricted activities.

PMID- 21188010
TI  - Laparoscopic gastric partitioning gastrojejunostomy for an unresectable duodenal
      malignant tumor.
AB  - As a palliative bypass for unresectable gastric or periampullary cancer,
      gastrojejunostomy (GJ) is sometimes associated with postoperative delayed gastric
      emptying. We report the successful laparoscopic application of this procedure in
      a 78-year-old man with duodenal obstruction. Computed tomography revealed a mass
      in the duodenum along with multiple masses in the liver. A radiological image
      showed an ulcerative tumour in the third portion of the duodenum occluding the
      lumen. He was diagnosed as having an unresectable duodenal cancer with multiple
      liver metastases. He needed palliative bypass surgery. Laparoscopically, the
      stomach was partially divided using an endoscopic autosuture device, and end-to
      side GJ was performed successfully. He was given a normal diet on the fourth
      postoperative day, and there was no delayed gastric emptying. Laparoscopic
      gastric partitioning GJ is a feasible and safe procedure to prevent postoperative
      delayed gastric emptying in case of malignant duodenal obstruction.

PMID- 21188012
TI  - Menetrier's Disease with Gastrointestinal Bleed.

PMID- 21188011
TI  - Solitary pelvic kidney encountered during laparoscopic colectomy.
AB  - We report a case of solitary pelvic kidney encountered during laparoscopic
      colectomy. A 55-year-old man was admitted to undergo laparoscopic colectomy for
      an early sigmoid colon cancer, which had been detected after a polypectomy. The
      kidneys were not clearly visualized in their normal position by ultrasonography.
      During the operation, anomalous vessels in the presacral space and a mass covered
      with fatty tissue were identified. We converted the operation to a mini
      laparotomy, and on performing intraoperative ultrasonography a solitary pelvic
      kidney was detected. An anterior resection was performed without operative
      complications. Laparoscopic ultrasonography (LUS) and hand-assisted laparoscopic
      surgery (HALS) should be considered as feasible adjuvants, when difficult
      situations arise during laparoscopic colectomy. In case of uncertainty about
      anatomical orientation or identification, it is prudent to convert to open
      surgery thereby preventing intraoperative complications such as injury to
      anomalous vessels or the ureter.

PMID- 21188013
TI  - Laparoscopic splenectomy using conventional instruments.

PMID- 21188014
TI  - Genes matter!

PMID- 21188015
TI  - Why Henry III of Navarre's Hair Probably did not Turn White Overnight.
AB  - Although a rare event, sudden whitening of hair (canities subita) has reportedly
      affected a number of well-known historical figures, usually in relation to
      dramatic events in their lives. Although early accounts are substantiated by more
      recent case reports in scientific literature, we suspect that the phenomenon is
      not only used as a literary means in fiction, with the aim of dramatizing, but
      probably also in historical accounts. For this purpose, we examine the case
      history of Henry III of Navarre who allegedly turned white on the evening of the
      Saint Bartholomew's day massacre, and challenge this claim, due to
      inconsistencies in his biography, with the current pathophysiological
      understanding of canities subita.

PMID- 21188016
TI  - Automated Digital Image Analysis (TrichoScan(r)) for Human Hair Growth Analysis:
      Ease versus Errors.
AB  - BACKGROUND: TrichoScan((r)) is considered to be time-saving, easy to perform and
      consistent for quantifying hair loss/growth. Conflicting results of our study
      lead us to closely observe the image analysis, and certain repeated errors in the
      detection of hair were highlighted. AIMS: To assess the utility of TrichoScan in
      quantification of diffuse hair loss in males with androgenetic alopecia (AGA) and
      females with diffuse telogen hair loss, with regard to total hair density (THD),
      telogen and vellus hair percentages. MATERIALS AND METHODS: TrichoScan procedure
      was performed on 77 cases and 20 controls. RESULTS AND DISCUSSION: In the cases,
      THD decreased with increasing severity of alopecia. Surprisingly, more than 85%
      of the healthy volunteers had an unexplained abnormal telogen hair percentage of
      more than 20. Also, the telogen hair percentages were not significantly different
      between cases and controls. Also, 65% of the patients with advanced thinning of
      hair did not have the expected elevation of vellus hair percentages on TrichoScan
      evaluation. Multiple errors were highlighted in hair detection by the software.
      Errors were noted at the exit points of follicular ostia, at places where hair
      strand thickness was not uniform throughout its length, where there was crossing,
      overlapping of the neighboring strands, and when more than one hair emerged from
      a single ostium. CONCLUSION: TrichoScan is promoted as a validated and precise
      tool for measurement of hair growth parameters. Under certain conditions, it may
      seem suitable for clinical trials evaluating treatment response. We provide
      evidence that this is an overstatement. This study concludes that TrichoScan
      analyzed anagen/telogen hair detection is not optimal; moreover, there is
      overestimation of THD and the vellus hair percentage does not correlate with
      clinical severity of alopecia. The current form of TrichoScan, though easy to
      use, is error-prone and awaits refinement.

PMID- 21188017
TI  - Histopathologic profile of alopecia areata in Indian patients.
AB  - BACKGROUND: Alopecia Areata (AA) is a "non-scarring" alopecia that has an
      autoimmune basis. Though clinically distinctive, problems arise in diagnosis
      depending on the temporal stage of the disease at presentation; some of them
      progress to scarring alopecia and predicting its prognosis is difficult.
      Histological changes depend on the disease stage and site of the biopsy.
      OBJECTIVES: To describe the spectrum of histologic features in AA. MATERIALS AND
      METHODS: A prospective and retrospective study of H and E sections of all
      biopsies signed out as AA between 2001 and 2009 (20 cases) was undertaken.
      RESULTS: The diagnosis was made on vertical sections in all cases. The total
      number of hair follicles ranged from 1 to 24 with an average of 7 and comprised
      mainly terminal follicles. Vellus follicles were scanty. Anagen to non-anagen
      ratio was 1:1.62. Miniaturization of follicles was noted in five (25%) cases.
      Peribulbar inflammation was seen in all the cases with a dominance of
      lymphocytes. Perifollicular fibrosis was noted in 12 (60%) and pigment casts in 5
      (25%) cases. Scarring was seen in two cases. In these cases, a diagnosis of AA
      was rendered on the basis of even spacing of the fibrotic units and remnants of
      the catagenic basement membrane within the scars. The epidermis and
      interfollicular dermis were normal in all the cases. CONCLUSION: The most
      consistent features of AA are an increase in non-anagen terminal follicles and
      peribulbar lymphocytic infiltrate. The etiology can be determined even in cases
      that have progressed to scarring.

PMID- 21188018
TI  - Monilethrix: one step more on the ladder of cytogenetics.
AB  - Monilethrix is one of the hair shaft abnormalities with increased fragility of
      hair. Here we describe a ten-year-old girl with a history of hair loss and
      breakage of hair since three months of age, associated with keratosis pilaris
      along with an abnormal microscopic finding of a hair shaft. A cytogenetic study
      of the patient showed an unexpectedly high degree of Acrocentric association.

PMID- 21188020
TI  - Essentials of Hair Care often Neglected: Hair Cleansing.
AB  - Why does the selection of hair cleansing products and conditioners seem complex?
      Why are there clear, opalescent, green, blue, glittery, cheap, expensive, thick,
      thin, fragrant, and unscented varieties of shampoos and conditioners? Why the
      whole cleansing process cannot be simplified by using the same bar soap used on
      the body for the hair? Does the shampoo selected really make a difference? What
      can a conditioner accomplish?

PMID- 21188019
TI  - Effective treatment of folliculitis decalvans using selected antimicrobial
      agents.
AB  - Folliculitis Decalvans (FD) is a rare neutrophilic infammation of the scalp
      characterized by painful, recurrent purulent follicular exudation resulting in
      primary cicatricial alopecia. However, unclear etiology makes FD treatment a
      difficult task. A wide variety of topical and systemic agents have been tried
      previously, with varied results. We present here a case series report of a set of
      13 patients with FD on antimicrobial therapy.

PMID- 21188021
TI  - Endocrinology of hirsutism.
AB  - Hirsutism represents a primary clinical indicator of androgen excess. The most
      common endocrine condition causing hirsutism is polycystic ovary syndrome (PCOS).
      Diagnosing PCOS is not easy as the signs and symptoms are heterogenous. The
      newest diagnostic guideline made by the Androgen Excess and PCOS Society in 2006,
      claims the presence of hyperandrogenism, and ovarian dysfunction (oligo /
      anovulation and / or polycystic ovaries). Obesity associated reproductive and
      metabolic dysfunctions may aggravate the symptoms of PCOS. PCOS might be
      underdiagnosed in non obese women because lean PCOS phenotypes might be
      underestimated for the syndrome. Effective medical treatment of PCOS and
      associated hirsutism depends on the endocrinological expertise and experience of
      the therapist in each individual case. An algorithm for the treatment has not
      been established yet.

PMID- 21188022
TI  - Topical immunotherapy in alopecia areata.
AB  - Alopecia Areata (AA) is a common non-scarring alopecia directed against the
      anagenic hair follicle. Various treatment modalities have been used for the
      treatment of severe AA. Topical immunotherapy is the best documented treatment so
      far for severe and refractory AA. Dinitrochlorobenzene (DNCB), squaric acid
      dibutylester (SADBE), and diphencyprone (DPCP) are the contact allergens used for
      this purpose. DNCB has been found to be mutagenic by the Ames test and is largely
      replaced by DPCP and SADBE. DPCP and SADBE are both known to be non-mutagenic
      compounds and have comparable efficacy results and relapse rates. SADBE requires
      special solvents and additives to maintain its potency and is more expensive than
      the rest. DPCP has a response rate varying from 60% in severe Alopecia Areata to
      17% in patients with alopecia totalis or universalis, and shows about 88 to 100%
      high response rate in patients with patchy Alopecia Areata.

PMID- 21188023
TI  - Ethics in trichology.
AB  - Today, trichology as a science is offered by reputed institutes worldwide with a
      planned curriculum of theory and clinical exposure. Non-medical trichologists,
      with rare exceptions, continue to lure the public with unscientific methods. A
      qualified dermatologist equipped with knowledge of hair biology is undoubtedly
      the most competent to deal with hair problems. We are all indisputably governed
      by a basic code of medical ethics as we are doctors first and last. Hence, a
      dermatologist/trichologist cannot have another set of ethics. Having said that,
      we cannot discount the fact that there are special clinical situations where
      guidelines already exist or need to be established with compliance to the base
      code of ethics.

PMID- 21188024
TI  - Controversy: Synthetic Hairs and their Role in Hair Restoration?
AB  - The subject of artifical hair fibers is controversial, in view of their chequered
      history and the ban by federal drug administration (FDA) on their use. This
      article analyzes different aspects of their use.

PMID- 21188025
TI  - Mesotherapy in Management of Hairloss - Is it of Any Use?
AB  - Mesotherapy has received a lot of publicity in the media and internet about its
      possible role in androgenetic alopecia. However, the subject is controversial in
      view of lack of documented evidence. This article provides a critical commentary
      on the use of mesotherapy in the management of androgenetic alopecia.

PMID- 21188026
TI  - Bioprospecting keratinous materials.
AB  - The concept of bioprospecting for bioactive peptides from keratin-containing
      materials such as wool, hair, skin and feathers presents an exciting opportunity
      for discovery of novel functional food ingredients and nutraceuticals, while
      value-adding to cheap and plentiful natural sources. The published literature
      reports multiple examples of proline-rich peptides with productive bio-activity
      in models of human disease including tumour formation, hypertension control and
      Alzheimer's disease. Bioactive peptides have been identified from food and other
      protein sources however the bioactivity of keratin-related proteins and peptides
      is largely unknown. Considering the high representation of proline-rich peptides
      among proven bioactive peptides, the proline-rich character of keratinous
      proteins supports current research. A selection of mammalian (cow epidermis,
      sheep wool) and avian (chicken feather) keratinous materials were subjected to
      enzymatic hydrolysis using established processing methods. A bio-assay of
      determining inhibition of early stage amyloid aggregation involved using a model
      fibril-forming protein - reduced and carboxymethylated bovine K-casein (RCMk-CN)
      and quantitation of fibril development with the amyloid-specific fluorophore,
      Thioflavin T (ThT). The assay was fully validated for analytical repeatability
      and used together with appropriate positive controls. Peptide library products
      derived from chicken feather (n=9), sheep wool (n=9) and bovine epidermis (n=9)
      were screened in the fibril inhibition assay based on K-casein. 3 of 27 products
      exhibited interesting levels of bio-activity with regard to fibril inhibition.
      HPLC profiles provide an indication of the complexity of the assemblage of
      peptides in the three active products. We conclude the bioprospecting research
      using keratinous materials shows promise for discovery of useful bioactive
      peptides.

PMID- 21188027
TI  - The many faces of trichotillomania.
AB  - Trichotillomania is a poorly understood complex disorder of multifaceted
      pathology which often requires an interdisciplinary approach for management.
      While sharing similarities with obsessive-compulsive disorder, compelling
      differences between these have also been noted. We present three cases of
      trichotillomania highlighting the remarkable variability seen in the presentation
      of this disorder. In doing so, we discuss on resolving the classificatory issues
      and call for a consensus on the understanding of the disorder.

PMID- 21188028
TI  - Naxos disease in two siblings.
AB  - Naxos disease is a rare cardiocutaneous disorder characterized by palmoplantar
      keratoderma, woolly hair and arrythmogenic right ventricular cardiomyopathy. We
      report two siblings with Naxos disease with right middle lobe syndrome in one of
      them.

PMID- 21188029
TI  - Monilethrix in pattern distribution in siblings: diagnosis by trichoscopy.
AB  - Monilethrix is a heritable hair shaft defect characterized by localized or
      diffuse alopecia resulting from hair fragility over friction areas, predominantly
      the temporal and occipital regions, and follicular keratosis over the occipital
      region. However, it lacks macroscopic features that enable easy and rapid
      diagnosis in medical practice. Hair shaft microscopy is the basis for diagnosing
      monilethrix. We present a report of two Indian male siblings aged 24 and 21, who
      presented with thinning and hair loss from the scalp in male pattern distribution
      and multiple skin-colored follicular papules over the nape of the neck and
      bilateral forearms since childhood. Trichoscopy of scalp hair revealed
      characteristic uniform elliptical nodes and intermittent constrictions along with
      variation in hair shaft diameter, presence of few vellus hair and yellow dots,
      suggesting a diagnosis of monilethrix with early-onset androgenetic alopecia.
      Dermoscopy of the papules revealed multiple stubs of broken hair arising from
      them with a similar beaded appearance, suggesting a diagnosis of monilethrix. The
      diagnosis of monilethrix was confirmed with light microscopy and hair clipping.
      This report highlights the patterned distribution of hair loss in monilethrix
      probably due to the early unmasking of androgenetic alopecia and the use of
      trichoscopy as the diagnostic modality.

PMID- 21188030
TI  - Diffuse neurofibroma of the scalp presenting as circumscribed alopecic patch.
AB  - Neurofibroma is a benign tumor of the peripheral nerve sheath characterized by
      proliferation of Schwann cells, perineural cells and endoneurial fibroblasts.
      Different types of neurofibromas can be identified, including localized,
      plexiform, and diffuse types. Diffuse neurofibroma is an uncommon form of
      neurofibroma that occurs primarily in children and young adults. The head and
      neck regions are the most common sites of involvement. Diffuse neurofibroma is an
      ill-defined infiltrative lesion and tends to involve the skin and subcutaneous
      tissues. It produces localized thickening and induration of the skin. We present
      a case of a 12-year-old boy who had a diffuse neurofibroma on the scalp since the
      age of 2 years.

PMID- 21188031
TI  - Intralesional steroids for alopecia areata.

PMID- 21188032
TI  - Bexarotene gel: a new topical therapy for alopecia areata.

PMID- 21188033
TI  - Is dandruff a disease?

PMID- 21188034
TI  - Chloroquine-induced Pruritus.
AB  - Chloroquine-induced pruritus remains one of the most common side-effects in the
      use of chloroquine in the prophylaxis and treatment of uncomplicated malaria
      before the advent of artemisinin-based combination therapies. It has been
      reported to vary from a tolerable to intolerable intensity among susceptible
      individuals resulting in disruption of treatment and development of resistance to
      the drug thus leading to therapeutic failures as reported. This scourge is quite
      challenging due to the complex physiologic mechanism that has not been fully
      elucidated. Factors observed to be responsible in the induction of pruritus such
      as age, race, heredity, density of parasitaemia; impurities in formulations,
      plasmodial specie, dosage form and metabolites have been discussed in this
      review. Efforts to ameliorate this burden have necessitated the use of drugs of
      diverse pharmacological classes such as antihistamines, corticosteroids and
      multivitamins either alone or as a combination. This review is to look into the
      use of chloroquine retrospectively, and consider its re-introduction due to its
      safety. Efficacy can be attained if the pruritic effect is resolved.

PMID- 21188036
TI  - Non-wood Fibre Production of Microcrystalline Cellulose from Sorghum caudatum:
      Characterisation and Tableting Properties.
AB  - The microcrystalline cellulose is an important ingredient in pharmaceutical,
      food, cosmetic and other industries. In this study, the microcrystalline
      cellulose, obtained from the stalk of Sorghum caudatum was evaluated for its
      physical and tableting characteristics with a view to assessing its usefulness in
      pharmaceutical tableting. The microcrystalline cellulose, obtained from the stalk
      of Sorghum caudatum, obtained by sodium hydroxide delignification followed by
      sodium hypochlorite bleaching and acid hydrolysis was examined for its
      physicochemical and tableting properties in comparison with those of the well
      known commercial microcrystalline cellulose grade, Avicel PH 101. The extraction
      yield of this microcrystalline cellulose, obtained from the stalk of Sorghum
      caudatum was approximately 19%. The cellulose material was composed of
      irregularly shaped fibrous cellulose particles and had a moisture content of 6.2%
      and total ash of 0.28%. The true density was 1.46. The flow indices showed that
      the microcrystalline cellulose, obtained from the stalk of Sorghum caudatum
      flowed poorly. The hydration, swelling and moisture sorption capacities were 3.9,
      85 and 24%, respectively. Tablets resulting from these cellulose materials were
      found to be without surface defects, sufficiently hard and having disintegration
      time within 15 min. The study revealed that the microcrystalline cellulose,
      obtained from the stalk of Sorghum caudatum compares favourably with Avicel PH
      101 and conformed to official requirement specified in the British Pharmacopoeia
      1993 for microcrystalline cellulose.

PMID- 21188035
TI  - Optimization of luminescent assay for screening of cyclin-dependent kinase 2
      inhibitors.
AB  - Cyclin-dependent kinases are most extensively studied targets for cancer
      chemotherapy since the tumor cells exhibit false checkpoints and can proliferate
      even if the genome is compromised. Cyclin-dependent kinases ensure the tight
      regulation of the cell cycle execution by mediating phosphorylation of cellular
      proteins. Deregulation of the cyclin-dependent kinase 2 activity by cellular and
      external factors leads to many diseases like cancers. Different methods like
      radiolabeled, fluorescence and luminescence are available for screening of
      library of compounds against kinases. However, bioluminescent methods offer
      several advantages like low background and no effect of fluorescent compound
      interference. Present study is focused on development, optimization and
      validation of cyclin-dependent kinase 2 assay which is suitable for
      identification potent and selective, ATP competitive and non-competitive
      inhibitors of cyclin-dependent kinase 2. The aim of present investigation was to
      optimize the assay for cyclin-dependent kinase 2/cylin A and cyclin-dependent
      kinase 2/cyclin E with use of bioluminescence based biochemical reaction. Both
      cyclin-dependent kinase 2 which are cyclin-dependent kinase 2/cyclin A and cyclin
      dependent kinase 2/cyclin E complexes, have different affinity for ATP.
      Therefore, both isoform analogs of cyclin-dependent kinase 2 were optimized
      separately. Optimum cyclin-dependent kinase 2/cyclin A and cyclin-dependent
      kinase 2/cyclin E concentration were found to be 250 ng/well and 200 ng/well,
      respectively. Optimum substrate (histone H1) concentration was found to be 2.5
      mg/ml for both cyclin-dependent kinase 2 analogs. Optimum reaction time was found
      to be 20 min for both cyclin-dependent kinase 2/cyclin complexes.

PMID- 21188037
TI  - Determination and Validation of Zonisamide and its Four Related Substances by
      HPLC and UV-Spectrophotometry.
AB  - A selective and sensitive liquid chromatographic method has been developed for
      simultaneous determination of zonisamide and its four related substances in
      pharmaceutical dosage forms. The assay involved an isocratic elution in
      perfectsil Target C18 column using a mobile phase composition of disodium
      hydrogen phosphate buffer, acetonitrile and methanol (650:150:200 v/v, pH
      adjusted to 3+/-0.05) with flow rate 1.2 ml/min and analyte monitored at 240 nm.
      Also a simple and precise spectrophotometric method was developed for dissolution
      studies. These proposed methods are sensitive, accurate, reproducible and useful
      for the routine determination of zonisamide in pharmacy.

PMID- 21188038
TI  - Development and Validation of a Reversed-phase HPLC Method for the Determination
      of Hydroxybenzene in a Cream Formulation.
AB  - A rapid, sensitive and specific reversed-phase high performance liquid
      chromatographic method with diode-array detection has been developed and
      validated for the determination of hydroxybenzene (0.494%, w/w) in a commercially
      available cream pharmaceutical formulation. Isocratic chromatography was
      performed on a C18 column with methanol-water 60:40 (v/v) containing 0.1%
      phosphoric acid (v/v) as mobile phase at a flow rate of 1.0 ml/min. UV detection
      was at 254 nm. Linearity of the method was excellent (r(2) = 0.9999). The
      relative standard deviation values for intra- and inter-day precision studies
      were < 1% and the recovery of hydroxybenzene was >99%. The limit of detection and
      quantitation for hydroxybenzene was found to be 13.5 eta g/ml and 2 MUg/ml,
      respectively. The method was also validated for specificity and robustness. The
      method was found to be robust and can be reliably used to determine the
      hydroxybenzene content of marketed formulations.

PMID- 21188039
TI  - Development and Validation of a RPLC Method for the Determination of 2
      Phenoxyethanol in Senselle Lubricant Formulation.
AB  - A new and simple reversed-phase liquid chromatographic method has been developed
      and validated for the determination of 2-phenoxyethanol preservative (0.3%, w/w)
      in senselle lubricant formulation. The separation was achieved with acetonitrile
      tetrahydrofuran-water (21:13:66, v/v/v) as mobile phase, a C(8) column, and UV
      detection at 258 nm. The calibration curve is linear (r(2)= 0.9999) from 20-140%
      of the analytical concentration of 0.75 mg/ml. The mean percent relative standard
      deviation values for intra- and inter-day precision studies are <1%. The recovery
      of 2-phenoxyethanol ranged between 99.76 and 100.03% from lubricant formulation.
      The limits of detection and quantitation are determined to be 0.094 and 0.15
      mg/ml, respectively. The method was found to be robust and can be successfully
      and reliably used to determine the 2-phenoxyethanol preservative content of
      marketed formulations.

PMID- 21188040
TI  - Study of the Complexation Behaviour of Fexofenadine with beta-Cyclodextrin.
AB  - Fexofenadine is a selective histamine H(1) receptor antagonist, used for relief
      of the symptoms of allergy. However its aqueous solubility is very poor. Solid
      inclusion complexes of fexofenadine and beta-cyclodextrin were prepared at the
      molar ratios of 1:1 and 1:2 by kneading, and coprecipitation methods to improve
      its solubility. Characterization of the complexes was performed using infrared
      spectroscopy, X-ray diffractometry, and in vitro dissolution studies.
      Fexofenadine was found to exhibit interaction with beta-cyclodextrin both in
      solid and liquid state. Phase solubility studies indicated that fexofenadine
      forms a stable complex with beta-cyclodextrin. Both IR spectroscopy and X-ray
      diffractometry studies indicated interaction of fexofenadine with beta
      cyclodextrin. Kneading method at 1:1 and co-precipitation method at 1:1 and 1:2
      molar ratios showed significant interaction. In vitro dissolution studies
      confirmed the same results.

PMID- 21188041
TI  - Binding modes of 2,4-diaminoquinazoline and 2,4-diaminopteridine analogs to P.
      falciparum dihydrofolate reductase enzyme: Molecular docking studies.
AB  - A molecular docking study was carried out on 28 compounds belonging to 2,4
      diaminoquinazoline and 2,4-diaminopteridine analogs using Glide, FlexX and GOLD
      programs and the X-ray crystallographic structures of the quadruple mutant
      (1J3K:pdb) and wild type (1J3I:pdb) Plasmodium falciparum dihydrofolate reductase
      enzyme. The experimental conformation the bound ligand WR99210 was precisely
      reproduced by the docking procedures as demonstrated by low (<2.00 A) root-mean
      square deviations. The results indicated that most of the compounds dock into the
      active sites of both the wild type and quadruple mutant P. falciparum
      dihydrofolate reductase enzymes. Visual inspection of the binding modes also
      demonstrated that most of the compounds could form H-bond interactions with the
      key amino acid residues (Asp54, Ile14 and Leu/Ile164) and with better docking
      scores than the bound compound (5). Their long side chains orient in the
      hydrophobic portion of the active site which is occupied by trichloro aryloxy
      side chain of WR99210 (5). Thus, avoid potential steric clashes with Asn108
      (mutated from Ser108). Such a clash is known to be responsible for the resistance
      of the P. falciparum to pyrimethamine and cycloguanil.

PMID- 21188042
TI  - Medicinal Plants Used in Wound Care: A Study of Prosopis africana (Fabaceae) Stem
      Bark.
AB  - The effects of the methanol extract of the stem bark of Prosopis africana
      (Guill., Perrott. and Rich.) Taubert (Fabaceae) on bleeding/clotting and
      coagulation time, excision and dead space wounds were studied in rats. Also, the
      extract was subjected to antibacterial, and acute toxicity and lethality (LD(50))
      tests. The extract significantly (P<0.05) reduced bleeding/clotting and
      coagulation time in rats. It also reduced epithelialization period of excision
      wounds in rats and inhibited the growth of laboratory strains of Staphylococcus
      aureus, Bacillus subtilis, Salmonella typhi, Pseudomonas aeruginosa and
      Klebsiella pneumoniae to varying extents. Acute toxicity and lethality (LD(50))
      test on the extract established an LD(50) of 774 mg/kg (i.p) in mice while
      phytochemical analysis gave positive reactions for alkaloids, saponins, tannins,
      flavonoids, steroids, terpenoids and carbohydrates. The results of this study
      demonstrate the beneficial effects of the stem bark of P. africana in wound care.

PMID- 21188043
TI  - In vitro Evaluation of Terminalia arjuna on Calcium Phosphate and Calcium Oxalate
      Crystallization.
AB  - Urinary stones are one of the oldest and the most common afflictions in humans.
      This disease has tormented humans since the earliest records of civilization. Ten
      percent of men and 3 % of women have a stone during their adult lives. Calcium
      containing stones are the most common comprising about 75 % of all urinary
      calculi, which may be in the form of pure calcium oxalate (50 %) or calcium
      phosphate (5 %) or a mixture of both (45 %). A number of plants have been
      mentioned in the Indian ayurvedic system, which plays a vital role in the
      inhibition of kidney stones. In the present study, the inhibitory potency of
      crude extracts or fractions of successive solvent extractions of Terminalia
      arjuna bark was evaluated on various stages of formation of calcium phosphate and
      on the growth of calcium oxalate monohydrate crystals in vitro. Results obtained
      indicated that Terminalia arjuna bark has the potential to inhibit the formation
      of both calcium phosphate and calcium oxalate crystals in vitro. Butanol fraction
      of Terminalia arjuna extract was the most effective in inhibiting formation of
      calcium phosphate and calcium oxalate crystals in vitro.

PMID- 21188044
TI  - Preparation and In vitro / In vivo characterization of spray dried microsphere
      formulation encapsulating 4-chlorocurcumin.
AB  - The objective of the present study was to prepare and characterize in vitro and
      in vivo performance of a sustained release microsphere formulation of 4
      chlorocurcumin, a novel curcumin analogue. A spray dried technique with
      ethylcellulose as the polymer was used in the preparation of these microspheres.
      Microspheres were characterized for drug content, particle size and shape, in
      vitro drug release and the drug-polymer interaction. To assess in vivo
      performance, both pharmacokinetics and hepatoprotective activity were
      investigated. Results were compared with an equivalent i.v. solution. The
      microspheres of 4-chlorocurcumin with ethylcellulose were successfully prepared
      using a spray-dried technique. These microspheres were able to sustain the
      release of the drug both in vitro as well as in vivo. Microspheres offered better
      pharmacokinetic and hepatoprotective properties to the drug compared to its
      solution form.

PMID- 21188045
TI  - Sub-chronic Hepatotoxicity of Anacardium occidentale (Anacardiaceae) Inner Stem
      Bark Extract in Rats.
AB  - The extracts of Anacardium occidentale have been used in the management of
      different cardiovascular disorders in Nigeria. These have necessitated the
      assessment of the toxicity of this plant extract in sub-chronic administration.
      The inner stem bark of Anacardium occidentale was extracted with 80 % methanol
      and quantitatively analysed for antinutrients and some heavy metals. The
      phytochemical compositions and acute toxicity of the extract were determined
      also. Toxicity profiles of the extract on some liver function parameters were
      evaluated following a sub-chronic oral administration at doses of 1.44 and 2.87
      g/kg. The phytochemical screening of extract revealed the presence of high amount
      of tannins, moderate saponins and trace of free reducing sugars. The antinutrient
      levels were 5.75 % (tannins), 2.50 % (oxalates), 2.00 % (saponins), 0.25 %
      (phytate) and 0.03 % (cyanide). The quantity of iron detected from dried crude
      was 8.92 mg/100 g, while lead and cadmium were non-detectable. The extract had
      LD(50)of 2.154g/kg p.o. in mice. Sub-chronic administration of the extract
      significantly increased the serum levels of alanine aminotransaminase and
      aspartate aminotransaminase, which are indicative of liver damage. The serum
      levels of alkaline phosphatase and total protein of the treated animals were not
      significantly increased. The effects of sub-chronically administered extract on
      hepatocytes were minimal as the serum alkaline phosphatase; total bilirubin and
      total protein levels in treated animals were not significant (p< 0.05). Thus, sub
      chronic administrations of Anacardium occidentale inner stem bark extract did not
      significantly (p< 0.05) depress the function of hepatocytes in Wistar rats.

PMID- 21188046
TI  - Microwave assisted synthesis and biological activity of novel
      coumarinyltriazolothiadiazoles.
AB  - A series of new 3-(4-methylcoumarinyl-7-oxymethyl)-6-substitutedphenyl-5,6
      dihydro-s-triazolo (3,4-b)(1,3,4)-thiadiazoles 2(a-j) have been synthesized by
      reacting 5-(4-methyl coumarinyl-7-oxymethyl)-4-amino-3-mercapto(4H)-1,2,4
      triazole with various aromatic aldehydes by microwave assisted organic synthesis.
      The structure of the compounds 2 (a-j) has been confirmed by IR, (1)H NMR and
      mass spectral data. All the compounds were screened for antimicrobial and
      antioxidant activity. Among the compounds tested, compounds 2d (4-dimethyl amino
      phenyl derivative) and 2h (3,4-dimethoxy phenyl derivative) showed better
      antimicrobial and antioxidant activity than rest of the compounds in the series.

PMID- 21188047
TI  - Isolation and characterization of a process impurity in tizanidine hydrochloride.
AB  - A new process impurity was detected during the HPLC analysis of Tizanidine
      hydrochloride (I) batches. The impurity (II) was isolated by preparative HPLC and
      characterized by NMR and Mass spectral analysis as 5-S-ethyl-N-(4,5-dihydro-1H
      imidazol-2-yl)-2,1,3-benzothiadiazol-4-amine hydrochloride.

PMID- 21188048
TI  - Design and Synthesis of Some Novel 4-(4-substituted aryl) Semicarbazones as
      Anticonvulsant Agents.
AB  - In the present study, a series of 4-(4-substituted aryl) semicarbazones were
      synthesized from substituted anilines and subsequently evaluated for their
      anticonvulsant activities. The anticonvulsant activities were established by the
      anticonvulsant drug development (ADD) programme NIH, USA using experimental
      animal, adult male FCM mice (20-25 g) and adult Sprague-Dawley rats (100-150 g)
      and screened against electroshock seizure, subcutaneous metrazole and minimal
      neurotoxicity tests in mice. Compound 7 was found equipotent to carbamazepine in
      both MES and ScPTZ tests. This study has highlighted the importance of distal
      alkyl chain which influences the anticonvulsant activity.

PMID- 21188049
TI  - Comparative study of proton pump inhibitors on dexamethasone plus pylorus
      ligation induced ulcer model in rats.
AB  - The present study was designed to compare ulcer protective effect of proton pump
      inhibitors viz. omeprazole, rabeprazole and lansoprazole against dexamethasone
      plus pylorus ligation induced ulcer model. Dexamethasone (5 mg/kg) was used as an
      ulcerogen. Dexamethasone suspended in 1% CMC in water was given orally to all the
      rats 15 min after the pylorus ligation. Omeprazole (20 mg/kg), rabeprazole (20
      mg/kg), and lansoprazole (20 mg/kg) were administered by oral route 30 min prior
      to ligation was used for ulcer protective studies, gastric secretion and mucosal
      studies. Effects of proton pump inhibitors were determined by the evaluation of
      various biochemical parameters such as ulcer index, free and total acidity,
      gastric pH, mucin, pepsin and total proteins. Oral administration of proton pump
      inhibitors showed significant reduction in gastric acid secretion and ulcer
      protective activity against dexamethasone plus pylorus ligation induced ulcer
      model. The % protection of omeprazole, rabeprazole and lansoprazole was 84.04,
      89.36 and 79.78, respectively. Rabeprazole significantly inhibited the acid
      pepsin secretion and increased the gastric mucin secretion. The observations made
      in the present study suggest that rabeprazole is the most effective gastric
      antisecretory and ulcer healing agent as compared to omeprazole and lansoprazole.

PMID- 21188050
TI  - Evaluation of Antiseizure Activity of Essential Oil from Roots of Angelica
      archangelica Linn. in Mice.
AB  - In the present study, the effect of essential oil of the root of Angelica
      archangelica Linn. was evaluated against electrically and chemically induced
      seizures. The seizures were induced in mice by maximal electroshock and
      pentylenetetrazol. The effect of essential oil of the root of Angelica
      archangelica on seizures was compared with standard anticonvulsant agents,
      phenytoin and diazepam. The essential oil of the root of Angelica archangelica
      suppressed duration of tonic convulsions and showed recovery in maximal
      electroshock induced seizures while it delayed time of onset of clonic
      convulsions and showed mortality protection in pentylenetetrazol induced
      seizures. The essential oil of the root of Angelica archangelica also produced
      motor impairment at the antiseizure doses. The study indicated that the essential
      oil exhibited antiseizure effect. The antiseizure effect may be attributed to the
      presence of terpenes in the essential oil.

PMID- 21188051
TI  - Anticonvulsant Activity of Schiff Bases of 3-Amino-6,8-dibromo-2-phenyl
      quinazolin-4(3H)-ones.
AB  - Schiff bases (9a-l) of 3-amino-6,8-dibromo-2-phenyl-quinazolin-4-(3H)-ones (8)
      with various substituted aldehydes were obtained by refluxing 1:1 molar
      equivalents of the reactants in dry ethanol for 6 h. The aminoquinazoline (8) was
      inturn obtained from 3,5-dibromoantharlinic acid via intermediate (7). All the
      synthesized compounds (9a-l) were evaluated for their anticonvulsant activity on
      albino mice by maximal electroshock method using phenytoin as a standard. The
      compound (9l) bearing a cinnamyl function displays a very high activity (82.74 %)
      at dose level of 100 mg/kg b.w.

PMID- 21188052
TI  - Microwave-assisted Synthesis of an Important Intermediate of Benazepril.
AB  - Rapid and efficient methods for the synthesis of an important intermediate of
      benazepril ethyl 3-phthalimido-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one-1
      acetate under the influence of microwave irradiation are described. A comparative
      study of conventional and microwave assisted method is briefly discussed.

PMID- 21188053
TI  - A Stability-indicating HPLC Method for Assay of Lercanidipine Hydrochloride in
      Tablets and for Determining Content Uniformity.
AB  - A simple, precise and accurate HPLC method has been developed and validated for
      assay of lercanidipine hydrochloride in tablets and for determination of content
      uniformity. An isocratic separation was achieved using a Chromasil YMC Pack C(8),
      150 * 4.6 mm i.d., 5um particle size columns with a flow rate of 1 ml/min and
      using a UV detector to monitor the elute at 240 nm. The mobile phase consisted of
      0.02 M ammonium dihydrogen phosphate buffer:methanol (35:65, v/v) with pH 3.5
      adjusted with phosphoric acid. The method was validated for specificity,
      linearity, pre-cision, accuracy, robustness and solution stability. The
      specificity of the method was deter-mined by assessing interference from the
      placebo and by stress testing of the drug (forced degradation). The method was
      linear over the concentration range of 20-80 ug/ml (r(2)= 0.9992) with a limit of
      detection and quantitation of 0.1 and 0.3 ug/ml respectively. Intraday and
      interday system and method precision were determined and accuracy was between
      99.3-101.9 %. The method was found to be robust and suitable for assay of
      lercanidipine hydrochloride in a tablet formulation and for determination of
      content uniformity. Degradation products resulting from the stress studies did
      not interfere with the detection of lercanidipine hydrochloride and the assay is
      thus stability-indicating.

PMID- 21188054
TI  - RP-HPLC Method for Simultaneous Estimation of Frusemide and Amiloride
      Hydrochloride in Tablet Formulation.
AB  - A new reverse phase high performance liquid chromatography method for the
      simultaneous estimation of frusemide and amiloride hydrochloride in tablet
      formulation is developed. The determination was carried out on a HIQ SIL, C18
      (250*4.6 mm, 5 um) column using a mobile phase of 50 mM phosphate buffer
      solution:acetonitrile (50:50 v/v, pH 3.0). The flow rate was 1.0 ml/min with
      detection at 283 nm. The retention time for frusemide was 3.038 min and for
      amiloride hydrochloride 10.002 min. Frusemide and amiloride hydrochloride showed
      a linear response in the concentration range of 20-200 ug/ml and 10-100 ug/ml,
      respectively. The results of analysis have been validated statistically and by
      recovery studies. The mean recoveries found for frusemide was 99.98% and for
      amiloride hydrochloride was 100.09%. Developed method was found to be simple,
      accurate, precise and selective for simultaneous estimation of frusemide and
      amiloride hydrochloride in tablets.

PMID- 21188055
TI  - Screening of Ethanol, Petroleum Ether and Chloroform Extracts of Medicinal
      Plants, Lawsonia inermis L. and Mimosa pudica L. for Antibacterial Activity.
AB  - Organic extracts (ethanol, petroleum ether and chloroform) of two medicinal
      plants Lawsonia inermis L. and Mimosa pudica L. were proven for antibacterial
      properties against 15 Gram-positive and Gram-negative human pathogenic bacteria.
      Among the three types of extracts tested, ethanol extract was found to possess
      maximum antibacterial activity. The diameter of the zone of inhibition of
      bacterial growth showed that Gram-negative bacteria are more sensitive than Gram
      positive bacteria to plant extracts. Between the two plants species studied,
      Lawsonia inermis extract showed more antibacterial activity compared to Mimosa
      pudica extract.

PMID- 21188056
TI  - Protective Effect of Ethanol Extract of Gymnosporia montana (Roth) Bemth. in
      Paracetamol-induced Hepatotoxicity in Rats.
AB  - The aim of the present study was to explore the hepatoprotective activity of the
      ethanol extract of leaves of Gymnosporia montana (Roth) Bemth. (Family:
      Celastraceous) against paracetamol-induced hepatotoxicity. Hepatotoxicity in
      Wistar rats was induced by a single intraperitoneal dose of 500 mg/kg of
      paracetamol and studied by comparing parameters such as serum glutamate
      oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline
      phosphatase and histopathological examination of liver. Pre and post-treatment
      with ethanol extract of Gymnosporia montana (Roth) Bemth. at doses of 50 and 100
      mg/kg was studied by comparing the above mentioned parameters with silymarin (100
      mg/kg) as standard. Both doses of ethanol extract of Gymnosporia montana (Roth)
      Bemth. were found to be hepatoprotective. Extract at the dose of 100 mg/kg
      produced effects comparable to those of silymarin. The present study indicates
      that alcohol extract of Gymnosporia montana (Roth) Bemth. possessed significant
      hepatoprotective activity.

PMID- 21188057
TI  - Effect of Plant Extracts Formulated in Different Ointment Bases on MDR Strains.
AB  - Extracts of Aloe vera whole plant, Eucalyptus globulus leaves, Ficus infectoria
      bark, Ficus religiosa bark and Piper betel leaves were studied for antibacterial
      activity on resistant and sensitive strains, isolated from skin and soft tissue
      infections. A combination of hot alcoholic extracts of Ficus infectoria, Ficus
      religiosa and Piper betel were found to be more effective against all the
      isolates. The combined extract was formulated in different ointment bases such as
      polyethylene glycol, gelatin, sodium alginate, carbopol, cream base and honey.
      These were then evaluated to find a suitable base for preparation of an ointment.
      In vitro study of the release of antimicrobials and kill-time studies of the
      herbal ointments was carried out against multi-drug resistant isolate of
      Pseudomonas. The ointment showed bactericidal activity within 2 h against the
      resistant strain of Pseudomonas spp.

PMID- 21188058
TI  - Rapid liquid chromatographic method for the determination of roflumilast in the
      presence of degradation products.
AB  - A forced degradation study on roflumilast drug substance was conducted under the
      conditions of hydrolysis, oxidation, thermal and photolysis. The method was
      developed and optimized by analyzing forcefully degraded samples. The best
      separation was achieved on a Zorbax SB C18 1.8 um column with 0.005 M ammonium
      formate buffer pH 3.5 and acetonitrile as mobile phase in a 13 min run time. The
      proposed method was able to resolve all the possible degradation products formed
      during stress study. The drug was stable to neutral, thermal and photolytic
      conditions but unstable to acidic, alkaline and oxidative conditions at 80
      degrees  for 24 h. The degradation products resulting from stress study did not
      interfere in assay and related substances of roflumilast and thus the method can
      be regarded as stability indicating. An alternate method was also developed on a
      conventional 250*4.6 mm, 5 um column wherein runtime was 38 min. Thus rapid
      resolution high throughput column was able to reduce the run time from 38 min to
      13 min.

PMID- 21188059
TI  - Use of drugs and cost of treatment of diarrhea in secondary level government
      hospitals in maharashtra.
AB  - A prescription audit was carried out among the outpatient attendees of 31
      secondary level hospitals under Maharashtra Health Systems Development Project.
      Use of drugs and cost of treatment of diarrhoea were studied using the
      prescriptions for diarrhoea collected for the prescription audit. Average number
      of drugs prescribed per prescription for treatment of diarrhoea was 3.7. It was
      higher than average number of drugs per prescription in the Maharashtra Health
      Systems Development Project hospitals in general. About three fourths of the
      prescriptions contained oral rehydration salts. Furazolidone and metronidazole
      were prescribed in about half of the prescriptions. Cotrimoxazole was prescribed
      in about one fourth of prescriptions. About 60% of the prescriptions contained
      other drugs. The average cost of prescription for diarrhoea was Rs. 14 and
      increased with the number of drugs prescribed. Average cost of prescription was
      the highest for those written by general practitioners. Pathological tests were
      indicated only in case of 11%.

PMID- 21188060
TI  - SPECT-CT: Technology trail.

PMID- 21188061
TI  - Regulatory requirements for designing PET-CT facility in India.

PMID- 21188062
TI  - Efficacy of SPECT over planar bone scan in the diagnosis of solitary vertebral
      lesions in patients with low back pain.
AB  - BACKGROUND: The purpose of our study has been to evaluate the efficacy of single
      photon emission computed tomography (SPECT) over planar bone scan in identifying
      solitary vertebral lesions in patients with low backache and its ability to
      differentiate various pathologies according to the uptake pattern. MATERIALS AND
      METHODS: The study included twenty patients out of whom six patients presented
      with known carcinoma and fourteen patients with low back pain. SPECT was done in
      all following planar skeletal survey. Benign and malignant lesions were
      identified according to the uptake pattern in vertebral elements, based on Gary
      F. Gates observations. Final diagnosis was obtained by means of biopsy or
      correlation with radiograph or computed tomography (CT) or magnetic resonance
      imaging (MRI), and / or follow up. RESULTS: SPECT detected additional 30% of
      solitary vertebral lesions that were obscured on planar scan. Seven out of twenty
      were localized in anterior vertebral body and were diagnosed as benign ostophytes
      in six and osteoma in one substantiating the previous observations. Out of six
      cases of known carcinoma, three were having solitary metastases and showed
      posterior vertebral body uptake with pedicle involvement. SPECT could localize
      specific lesions as source of pain in eleven patients with low back pain (78%)
      and identified various etiologies including benign tumors (osteoid osteoma and
      osteoma), facet arthritis, discitis, transverse process fractures and
      spondylolysis. CONCLUSION: Our study highlighted the higher diagnostic value of
      SPECT over planar skeletal scintigraphy in localizing solitary vertebral lesions
      in low backache patients. Based on SPECT pattern, malignant and benign lesions
      could be differentiated in the given clinical context.

PMID- 21188063
TI  - Estimation of effective half life of clearance of radioactive Iodine (I) in
      patients treated for hyperthyroidism and carcinoma thyroid.
AB  - BACKGROUND: In medical applications of radioisotopes, for calculations of whole
      body doses and radiation safety applications, there is a need to estimate
      radioactive body burden. Local recommendations in Oman stipulate the need for
      hospitalization of patients treated for radioactive-iodine ((131) I) with
      activities above 400 MBq. MATERIALS #ENTITYSTARTX00026; METHODS: A study of body
      burden estimation from sequentially measured exposure rates from patients treated
      for carcinoma thyroid and hyperthyroidism was undertaken. A digital auto-ranging
      beta gamma survey instrument calibrated for measurement of exposure rates is used
      in this study. RESULTS: The mean measured exposure rates at 1 m in MUSv/h
      immediately after administration and at 24 h intervals are used for estimation of
      effective half time of clearance of administered activity. For patients with post
      operative thyroid carcinoma, the variation of body burden with time post
      administration indicated tri-exponential clearance pattern, with T(1/2eff) values
      14.4 h, 22 h, and 41.3 h. For patients treated for thyrotoxicosis, the body
      burden showed slow delayed clearance with a T(1/2eff) - 111.4 h, and exposure
      rates did not show appreciable fall off after 48 h.

PMID- 21188064
TI  - Role of myocardial perfusion scintigraphy post invasive coronary angiography in
      patients with Myocardial Infarction.
AB  - BACKGROUND: The presence of severe hypokinesia or akinesia and near complete
      stenotic lesions on coronary angiography, in a patient with acute myocardial
      infarction raises a question of viability in the involved territory and its
      response to revascularization. The decision of revascularization can be
      effectively taken after myocardial perfusion scintigraphy (MPS). AIM: To evaluate
      the role of MPS in patients with acute or recent myocardial infarction after
      invasive coronary angiography. MATERIALS AND METHODS: Thirty-five patients (27
      Males, 8 Females; Mean age 54 years) with acute myocardial infarction, who
      underwent invasive angiography, were included prospectively. Invasive angiography
      was attempted during the episode of acute chest pain in 20 patients. Fifteen
      patients underwent angiography without MPS because of non-availability of MPS at
      the time of initial presentation in the referring hospital. Revascularization was
      deferred because of complete / near complete block of artery with hypokinesia /
      akinesia of the distal LV segments in 32 / 35 patients and 50 to 70% block in 3 /
      35. These patients were subjected to MPS. RESULTS: Twenty patients underwent
      stress MPS and 15 underwent nitrate-augmented rest re-distribution study (RR
      study). Imaging was performed using the hybrid SPECT / CT system. The average
      defect size of the perfusion defect was 34% (5 - 57% range). Sixteen patients
      (46%) had fixed perfusion defects. Reversible ischemia was present in 19 (54%).
      Ten patients had a < 10% reversible perfusion defect. Nine patients had
      reversible ischemia, > 10% of the LV myocardium, and underwent the invasive
      revascularization procedure. CONCLUSION: MPS is invaluable in patients who have
      total / near total occlusion of the coronary artery and distal segment
      hypokinesia or akinesia on invasive angiography. One in four patients, deemed to
      have non-viable myocardium, underwent an invasive revascularization after
      undergoing MPS.

PMID- 21188065
TI  - Does thyroxine suppression therapy help to rationalize surgery in benign
      euthyroid nodules?
AB  - BACKGROUND: Nodular thyroid disease is a common endocrine problem. Most thyroid
      nodules are benign hyperplastic lesions, but 5-20% may be a true neoplasm. It is
      important to differentiate a benign from a malignant nodule early as the approach
      to treatment in the two is radically different. Early institution of medical
      management in a benign nodule may obviate the need for surgery. PURPOSE OF THE
      STUDY: The present work aims to study the efficacy of thyroxine suppression in
      the management of benign thyroid nodules. MATERIALS AND METHODS: A prospective
      study on patients presenting with thyroid nodule was undertaken. The diagnostic
      work-up included a clinical evaluation, thyroid function tests, thyroid
      scintigraphy and fine needle aspiration cytology. Based on the investigations,
      patients were segregated in Group A (toxic nodular goiter), Group B (benign
      euthyroid nodule) and Group C (malignant nodule). Group A patients were managed
      with antithyroid drugs and radioiodine and Group C patients were managed
      surgically. Group B patients were put on thyroxine suppression. Patients who
      failed to show reduction in size of the nodule at 18 months were treated
      surgically. CONCLUSION: The response rate of benign euthyroid nodule to thyroxine
      suppression was 76% in the present study.

PMID- 21188066
TI  - Successful removal of intrathyroidal parathyroid adenoma diagnosed and accurately
      located preoperatively by parathyroid scintigraphy (SPECT-CT).
AB  - We describe the case of a large intrathyroidal parathyroid adenoma in a 46-year
      old woman who had a history of recently diagnosed hypercalcaemia and a 2-year
      history of an asymptomatic enlargement of the right lobe of the thyroid. This
      rare case highlights the potential difficulties that can arise in the evaluation
      of hyperparathyroidism, especially in cases of multinodular goiter. In some
      cases, including this one, even a thorough preoperative evaluation that includes
      radiological studies (ultrasonography and computed tomography [CT]) may not allow
      for a definitive preoperative diagnosis due to limited sensitivity, especially in
      multinodular goiter. The overlapping histological features between thyroid and
      parathyroid lesions can also be problematic at the time of the intraoperative
      frozen-section evaluation. We present a case in which, with parathyroid
      scintigraphy and combination of structural and functional imaging (SPECT-CT), we
      could accurately locate the intrathyroidal parathyroid adenoma in a patient with
      multinodular goiter.

PMID- 21188067
TI  - Hot tongue on FDG PET scan in a patient of Hodgkin's lymphoma undergoing
      antipsychotic treatment.
AB  - Fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography
      (F-18 FDG PET-CT) is the modality of choice for the diagnosis, staging, and
      restaging of many malignancies. The importance of eliminating false positives
      cannot be underestimated because they can dramatically alter the clinical course.
      We present a case of benign uptake in the tongue secondary to tardive dyskinesia
      in a 53-year-old woman referred for therapy response evaluation of Hodgkin's
      lymphoma who was concurrently receiving oral antipsychotic therapy. This case
      emphasizes the importance of detailed clinical history and examination when
      concluding definite diagnosis.

PMID- 21188068
TI  - TC MDP bone scan in evaluation of painful scoliosis.
AB  - A 18-year-old male presented with low back ache. The patient was investigated and
      was diagnosed to have painful scoliosis. X-ray and other examinations could not
      reveal any diagnosis. The patient was referred to undergo bone scan on clinical
      suspicion of osteoid osteoma and to rule out stress fracture if any. Planar bone
      scan was performed, which showed a lesion in L3 vertebra and was further
      evaluated with SPECT (Single photon emission computed tomography) study to
      characterize the lesion. On SPECT examination, the classical features of osteoid
      osteoma, the double density sign (11), was noted in the pars interarticularis
      region. These findings were confirmed by a CT scan, which showed a sclerotic
      lesion in pars interarticularis of L3 vertebra. The patient was posted for
      operation and was relieved of symptoms in the postoperative follow-up.

PMID- 21188069
TI  - Diffuse hepatic and splenic Tc-99m MDP tracer uptake in case of multiple myeloma.
AB  - Tc-99m methylene diphosphonate (MDP) bone scintigraphy has long been used for the
      evaluation of benign as well as malignant skeletal conditions. However, non
      osseous tracer uptake on a bone scan is an unusual finding. There is a need to
      understand the pathophysiological basis of the non-osseous uptake, which may have
      a clinical relevance or deteriorating effect on the quality of the bone scan. We
      describe a case of multiple myeloma, where extraosseous uptake in the form of
      diffuse hepatic and splenic uptake, with almost normal skeletal tracer
      distribution, has been seen on the bone scan.

PMID- 21188070
TI  - Water evaporation and conformational changes from partially solvated ubiquitin.
AB  - Using molecular dynamics simulation, we study the evaporation of water molecules
      off partially solvated ubiquitin. The evaporation and cooling rates are
      determined for a molecule at the initial temperature of 300 K. The cooling rate
      is found to be around 3 K/ns, and decreases with water temperature in the course
      of the evaporation. The conformation changes are monitored by studying a variety
      of intermediate partially solvated ubiquitin structures. We find that ubiquitin
      shrinks with decreasing hydration shell and exposes more of its hydrophilic
      surface area to the surrounding.

PMID- 21188071
TI  - Hyperhomocysteinaemia in Behcet's Disease.
AB  - Objectives. The aim of this study was to investigate if hyperhomocysteinaemia is
      a contributive risk factor for the pathogenesis and the activity of Behcet's
      disease (BD). Design and Methods. Fifty four patients fullfiling the criteria of
      the International Study Group for BD were enrolled. Fifty healthy volunteers
      matched for age and sex with the BD group were included as a negative control
      group. Patients, with any condition that might affect plasma homocysteine
      concentration, were excluded. Results. Mean serum homocysteine concentration was
      significantly higher in patients with BD than in the healthy controls (P < .001),
      in patients with active disease (P = .04), and in masculine gender (P = .05).
      There was no significant difference between homocysteine level and clinical
      involvement. Conclusions. We demonstrated that plasma total homocysteine level
      (tHcy) is increased in BD and correlated with disease activity. No association
      was found between homocysteine levels and clinical involvement.

PMID- 21188072
TI  - The Cell Wall Teichuronic Acid Synthetase (TUAS) Is an Enzyme Complex Located in
      the Cytoplasmic Membrane of Micrococcus luteus.
AB  - The cell wall teichuronic acid (TUA) of Micrococcus luteus is a long-chain
      polysaccharide composed of disaccharide repeating units [-4-beta-D-ManNAcAp-(1
      >6)alpha-D-Glcp-1-](n), which is covalently anchored to the peptidoglycan on the
      inner cell wall and extended to the outer surface of the cell envelope. An enzyme
      complex responsible for the TUA chain biosynthesis was purified and
      characterized. The 440 kDa enzyme complex, named teichuronic acid synthetase
      (TUAS), is an octomer composed of two kinds of glycosyltransferases,
      Glucosyltransferase, and ManNAcA-transferase, which is capable of catalyzing the
      transfer of disaccharide glycosyl residues containing both glucose and the N
      acetylmannosaminuronic acid residues. TUAS displays hydrophobic properties and is
      found primarily associated with the cytoplasmic membrane. The purified TUAS
      contains carotinoids and lipids. TUAS activity is diminished by phospholipase
      digestion. We propose that TUAS serves as a multitasking polysaccharide
      assembling station on the bacterial membrane.

PMID- 21188073
TI  - Evaluation of Serum Testosterone, Progesterone, Seminal Antisperm Antibody, and
      Fructose Levels among Jordanian Males with a History of Infertility.
AB  - Due to the biochemical complexity of seminal fluid, we attempt to study the
      possible correlation between fructose, which is secreted under the effect of
      androgen hormone, and autoimmunity, which might play a role in varicocele
      associated infertility, in reducing sperm motility. Seminal fructose, antisperm
      antibodies (ASAs) and blood steroids hormones (testosterone and progesterone)
      levels were measured in 66 infertile males with varicocele and 84 without
      varicocele referred for fertility treatment. Seminal analysis was performed with
      biochemical measurements of seminal fructose and mixed agglutination reaction
      (MAR) for ASA. Serum levels of progesterone and testosterone were estimated using
      a competitive chemoluminescent enzyme immunoassay. The mean values for serum
      testosterone were 380.74 +/- 24.331, 365.9 +/- 16.55, and 367.5 +/- 21.8 ng/dl,
      progesterone 0.325 +/- 0.243, 0.341 +/- 0.022, and 0.357 +/- 0.0306 ng/ml, and
      seminal plasma fructose 359.6 +/- 26.75, 315.6 +/- 13.08, and 332.08 +/- 24.38
      mg/dl in males with varicocele, without varicocele, and fertile males,
      respectively. A significant high level of testosterone was observed within
      varicocele group (P = .001). This result showed that testosterone may play a role
      as an infertility determinant in subjects with varicocele. ASA was detected in 18
      (26.47%) of cases with varicocele, 20 (38.46%) without varicocele, and in 16
      (32.0%) fertile men. Cases with ASAs associated with low sperm motility
      morphology. An inverse correlation between sperm-bound antibodies and viscosity
      has been shown (P = .017). ASA showed some significant inverse relations with
      ages, durations of infertility, and viscosity (P < .05). In addition, a
      significant correlation was observed between ASA positive seminal plasma and
      testosterone concentration among infertile cases (with or without varicocele) and
      fertile (P < .05). Our results suggest a relationship between testicular steroid
      hormone levels with autoimmunity and sperm antibodies which influence the
      motility of ejaculated spermatozoa among Jordanian infertile males.

PMID- 21188074
TI  - Cloning, Expression, and Purification of a Nitric Oxide Synthase-Like Protein
      from Bacillus cereus.
AB  - The nitric oxide synthase-like protein from Bacillus cereus (bcNOS) has been
      cloned, expressed, and characterized. This small hemeprotein (356 amino acids in
      length) has a mass of 43 kDa and forms a dimer. The recombinant protein showed
      similar spectral shifts to the mammalian NOS proteins and could bind the
      substrates L-arginine and N(G)-hydroxy-L-arginine as well as the ligand
      imidazole. Low levels of activity were recorded for the hydrogen peroxide
      dependent oxidation of N(G)-hydroxy-L-arginine and L-arginine by bcNOS, while a
      reconstituted system with the rat neuronal NOS reductase domain showed no
      activity. The recombinant bcNOS protein adds to the complement of bacterial NOS
      like proteins that are used for the investigation of the mechanism and function
      of NO in microorganisms.

PMID- 21188075
TI  - Enzymatic and mRNA Transcript Response of Ovine 6-Phosphogluconate Dehydrogenase
      (6PGD) in Respect to Different Milk Yield.
AB  - Ovine 6-phosphogluconate dehydrogenase (6PGD) is an enzyme of the pentose
      phosphate pathway, providing the necessary compounds of NADPH for the synthesis
      of fatty acids. Much of research has been conducted both on enzymatic level and
      on molecular level. However, to our knowledge, any correlation between enzymatic
      activity and 6PGD gene expression pattern related to different physiological
      stages has not been yet reported. With this report, we tried to highlight if any
      correlation between enzymatic activity and expression of ovine 6PGD gene exists,
      in respect to different milk yield. According to the determined enzymatic
      activities and adipocytes characteristics, ewes with low milk production
      possessed a greater (P <= .001) 6PGD activity and larger adipocytes than the
      highly productive ewes. Although 6PGD expression pattern was higher in low milk
      yield ewes than in ewes with high milk production, this difference was not found
      statistically significant. Thus, 6PGD gene expression pattern was not followed by
      so rapid and great/sizeable changes as it was observed for its respective
      enzymatic activity, suggesting that other mechanisms such as post translation
      regulation may be involved in the regulation of the respective gene.

PMID- 21188076
TI  - Inhaled Anesthetics Promote Albumin Dimerization through Reciprocal Exchange of
      Subdomains.
AB  - Inhaled anesthetics affect protein-protein interaction, but the mechanisms
      underlying these effects are still poorly understood. We examined the impact of
      sevoflurane and isoflurane on the dimerization of human serum albumin (HSA), a
      protein with anesthetic binding sites that are well characterized. Intrinsic
      fluorescence emission was analyzed for spectral shifting and self-quenching, and
      control first derivatives (spectral responses to changes in HSA concentration)
      were compared against those obtained from samples treated with sevoflurane or
      isoflurane. Sevoflurane increased dimer-dependent self-quenching and both
      decreased oligomer-dependent spectral shifting, suggesting that inhaled
      anesthetics promoted HSA dimerization. Size exclusion chromatography and
      polarization data were consistent with these observations. The data support the
      proposed model of a reciprocal exchange of subdomains to form an HSA dimer. The
      open-ended exchange of subdomains, which we propose occuring in HSA oligomers,
      was inhibited by sevoflurane and isoflurane.

PMID- 21188077
TI  - Identification and Partial Characterization of an L-Tyrosine Aminotransferase
      (TAT) from Arabidopsis thaliana.
AB  - The aminotransferase gene family in the model plant Arabidopsis thaliana consists
      of 44 genes. Twenty six of these enzymes are classified as characterized meaning
      that the reaction(s) that the enzyme catalyzes are documented using experimental
      means. The remaining 18 enzymes are uncharacterized and are therefore deemed
      putative. Our laboratory is interested in elucidating the function(s) of the
      remaining putative aminotransferase enzymes. To this end, we have identified and
      partially characterized an aminotransferase (TAT) enzyme from Arabidopsis
      annotated by the locus tag At5g36160. The full-length cDNA was cloned and the
      purified recombinant enzyme was characterized using in vitro and in vivo
      experiments. In vitro analysis showed that the enzyme is capable of
      interconverting L-Tyrosine and 4-hydroxyphenylpyruvate, and L-Phenylalanine and
      phenylpyruvate. In vivo analysis by functional complementation showed that the
      gene was able to complement an E. coli with a background of aminotransferase
      mutations that confers auxotrophy for L-Tyrosine and L-Phenylalanine.

PMID- 21188078
TI  - Purification and characterization of a mitogenic lectin from cephalosporium, a
      pathogenic fungus causing mycotic keratitis.
AB  - Ophthalmic mycoses caused by infectious fungi are being recognized as a serious
      concern since they lead to total blindness. Cephalosporium is one amongst several
      opportunistic fungal species implicated in ophthalmic infections leading to
      mycotic keratitis. A mitogenic lectin has been purified from the mycelia of
      fungus Cephalosporium, isolated from the corneal smears of a keratitis patient.
      Cephalosporium lectin (CSL) is a tetramer with subunit mass of 14 kDa,
      agglutinates human A, B, and O erythrocytes, and exhibits high affinity for mucin
      compared to fetuin and asialofetuin but does not bind to simple sugars indicating
      its complex sugar specificity. CSL showed strong binding to normal human
      peripheral blood mononuclear cells (PBMCs) to elicit mitogenic activity. The
      sugar specificity of the lectin and its interaction with PBMCs to exhibit
      mitogenic effect indicate its possible role in adhesion and infection process of
      Cephalosporium.

PMID- 21188079
TI  - Clearance in vivo of instilled [h]cholesterol from the rat lung.
AB  - Phospholipids and lung surfactant proteins are known to be recycled within the
      lung alveolus mainly by uptake into type II epithelial cells that secrete lipid
      enriched lung surfactant. Dipalmitoyl phosphatidylcholine (DPPC) is the major
      component of lung surfactant lipids and cholesterol is the second most abundant.
      However, cholesterol turnover in vivo has not been measured and it is not known
      how long steroidal compounds persist in the lung in intact animals. Here we
      report on experiments in which radiolabeled cholesterol was instilled into the
      lungs of rats, then at various postinstillation periods, radioactive sterols in
      lavage fluid, and in postlavage whole lungs were measured in individual animals.
      Radioactive sterols in the lungs remained high for a week and were still
      detectable 46 days later. The clearance rate during the initial postinstillation
      week was approximately 10% per day. Both radioactive free and esterified sterols
      were recovered from bronchoalveolar lavage fluid and postlavage lungs.

PMID- 21188080
TI  - Vascular guidance: microstructural scaffold patterning for inductive
      neovascularization.
AB  - Current tissue engineering techniques are limited by inadequate vascularisation
      and perfusion of cell-scaffold constructs. Microstructural patterning through
      biomimetic vascular channels within a polymer scaffold might induce
      neovascularization, allowing fabrication of large engineered constructs. The
      network of vascular channels within a frontal-parietal defect in a patient,
      originating from the anterior branch of the middle meningeal artery, was modeled
      using computer-aided design (CAD) techniques and subsequently incorporated into
      polycaprolactone (PCL) scaffolds fabricated using fused deposition modeling
      (FDM). Bone marrow-derived mesenchymal stem cells (MSCs) were seeded onto the
      scaffolds and implanted into a rat model, with an arteriovenous bundle inserted
      at the proximal extent of the vascular network. After 3 weeks, scaffolds were
      elevated as a prefabricated composite tissue-polymer flap and transferred using
      microsurgical technique. Histological examination of explanted scaffolds revealed
      vascular ingrowth along patterned channels, with abundant capillary and
      connective tissue formation throughout experimental scaffolds, while control
      scaffolds showed only granulation tissue. All prefabricated constructs
      transferred as free flaps survived and were viable. We term this concept
      "vascular guidance," whereby neovascularization is guided through customized
      channels in a scaffold. Our technique might potentially allow fabrication of much
      larger tissue-engineered constructs than current technologies allow, as well as
      allowing tailored construct fabrication with a patient-specific vessel network
      based on CT scan data and CAD technology.

PMID- 21188081
TI  - Preface to the First Issue, JCDR.

PMID- 21188082
TI  - Journal Of Cardiovascular Disease Research CURRENT EDITORIAL TEAM - 2010.

PMID- 21188083
TI  - The link between diabetes and atrial fibrillation: cause or correlation?

PMID- 21188084
TI  - Quinidine depresses the transmural electrical heterogeneity of transient outward
      potassium current of the right ventricular outflow tract free wall.
AB  - BACKGROUND#ENTITYSTARTX02014;: Electrical heterogeneity of the right ventricular
      outflow tract (RVOT) is regarded as one of the main electrophysiological
      substrates for Brugada syndrome. Recently quinidine has shown efficacy in
      patients with Brugada syndrome due to its ability to inhibit potassium current
      especially 4-aminopyridine-sensitive, non-Ca(2+) -dependent transient outward
      potassium current (Ito). However, much less is known on how extent quinidine in
      clinical therapeutic concentration range can inhibit this kind of electrical
      heterogeneity of RVOT Ito. METHODS AND RESULTS#ENTITYSTARTX02014;: Single RVOT
      free wall epicardial (Epi) cell, midmyocardial (M) cell and endocarcial (Endo)
      cells were used for whole-cell voltage clamping and Ito was recorded at 37
      degrees C, 0.2 Hz depolarization pulse. Evident Ito tranmural heterogeneity
      existed in RVOT free wall. Under the condition of baseline, of 10 MUM quinidine
      perfusion 5 minutes (mins), and of 10 MUM quinidine perfusion 7-10 mins, from 0
      mV to 70 mV the whole transmural average Ito values of RVOT free wall were 10.2
      pA/pF, 5.5 pA/pF and 3.5 pA/pF, respectively (between groups, P< 0.01). The
      inhibitory percentage of 10 MUM quinidine at 5 mins and 7-10 mins steady-state
      level on the the whole Ito transmural heterogeneity of RVOT free wall were
      46.3%+/-6% and 66.5%+/-11%, respectively. CONCLUSIONS#ENTITYSTARTX02014;: There
      exists a robust Ito transmural electrical heterogeneity in RVOT free wall and
      quinidine in clinical therapeutic concentration can depress this kind of
      heterogeneity effectively.

PMID- 21188085
TI  - Influence of valsartan-eluting stent on neointima formation.
AB  - OBJECTIVE: #ENTITYSTARTX02014; This study is to explore the effect of valsartan
      eluting stents on neointima formation after stenting and to elucidate possible
      mechanisms how locally used valsartan prevents in-stent restenosis (ISR). METHOD:
      valsartan- and carriereluting stents were manufactured by using multi-layer
      coated technology. Bare stents, carrier-eluting stents and valsartan- eluting
      stents were implanted into the abdominal aortas of the rabbits respectively.
      Quantitative angiography (QA) before, immediately after and 3 months after stent
      implantation were compared between the groups of bare (n=8), carrier-eluting
      (n=8) and valsartan-eluting stent (n=10), which allows the comparison of vascular
      diameters of aortas as well as indices of vascular neointimal formation, i.e.
      luminal area (LA), neointimal area (NIA), inner elastic membrane luminal area
      (IELA) and the maximal inner-membrane thickness (MIT) in 15 rabbits. alpha-Actin
      protein expression were detected by Envision two-step immunohistochemistry. Mean
      positive indices (MPI) of the above protein were analyzed semi-quantatively by
      IMS(Information Management System) cell image analysis system. MPI=positive
      area*OD (optical density). Collagen deposition in neointima was observed through
      MASSON stain among the three groups. RESULT: #ENTITYSTARTX02014; the mean aortic
      diameters were similar in the three groups:bare stents group(n=8), carrier
      eluting stents group(n=8) and valsartan eluting stents group(n=10) measured by QA
      at different time. A larger luminal area and a less neointimal hyperplasia in
      valsartan eluting-stents group was found compared with the other two groups. The
      mean luminal areas were 4345548+/-125822um(2); 4302061+/-167952 um(2); 5016269+/
      207934um(2) respectively. The mean neointimal areas were 1119635+/-163503um(2);
      1135636+/-136555um(2); 441577+/-74099um(2) and the mean maximal inner-membrane
      thickness were 210+/-30um;192+/-21um; 116+/-12um respectively. alpha-Actin
      protein expression was significantly lower in neointima of valsartan eluting
      stents group than the other two groups. Through MASSON stain we found that
      Collagen was much richer in neointima of bare stents group and carrier-eluting
      stents group than valsartan eluting-stents group. CONCLUSION: #ENTITYSTARTX02014;
      Valsartan eluting-stents inhibited neointimal hyperplasia after stenting by
      decreasing collagen deposition and smooth muscle cell proliferation. Therefore it
      would be potentially effective in preventing in-stent restenosis. ABBREVIATIONS:
      #ENTITYSTARTX02014; Quantitative angiography (QA), luminal area (LA), neointimal
      area (NIA), inner elastic membrane luminal area (IELA), the maximal inner
      membrane thickness (MIT), Mean positive indices (MPI), optical density (OD),
      Drugeluting stents (DES), in-stent restenosis(ISR), percutaneous transluminal
      coronary angioplasty (PTCA), angiotensin alpha type 2 receptor (AT2).

PMID- 21188086
TI  - Circadian variation on the onset of acute ST segment elevation myocardial
      infarction in diabetic subjects.
AB  - BACKGROUND#ENTITYSTARTX02014;: Previous studies have shown that there is a
      circadian variation in the incidence of acute myocardial infarction. The aim of
      this study is to examine the circadian rhythms of acute myocardial infarction in
      patients with type 2 diabetes. METHODS AND RESULTS#ENTITYSTARTX02014;: 1016
      consecutive patients admitted to a coronary care unit with acute ST elevation
      myocardial infarction were studied from January 2004 to December 2008. All
      patients were divided into two groups according to with or without diabetes.
      Admission rates were calculated according to the 6-hour interval of the day
      (circadian rhythm). The data were analyzed for variations within subgroups. In
      diabetic group, number of patients in the first to fourth quarters was 38, 45,
      43, 46 respectively (NS). The corresponding figures for the controls were 174,
      295, 183, 192 (P<0.01). The difference between the two groups was significant
      (P<0.02). CONCLUSION#ENTITYSTARTX02014;: There is no a significant circadian
      variation in the onset of acute myocardial infarction in diabetic subjects.

PMID- 21188087
TI  - Cardiac findings in acute yellow oleander poisoning.
AB  - BACKGROUND: #ENTITYSTARTX02014; The Yellow Oleander is an ornamental tree that is
      common throughout the tropics. Ingestion of its seeds results in a clinical
      picture similar to digoxin toxicity. OBJECTIVES: #ENTITYSTARTX02014; The aim of
      this study was to evaluate cardiac findings in acute Yellow Oleander poisoning.
      METHODS AND MATERIALS: #ENTITYSTARTX02014; A total of 21 patients with history of
      Yellow Oleander ingestion were enrolled in this study. RESULTS:
      #ENTITYSTARTX02014; All symptomatic patients had conduction defects affecting the
      sinus node, theatrio-ventricular node or both. Patients showing cardiac
      arrhythmias that required specific management had significantly higher serum
      potassium concentrations. CONCLUSION: #ENTITYSTARTX02014; Most of the symptomatic
      patients had conduction defects affecting sinus or atrio-ventricular nodes but
      few had atrial or ventricular arrhythmias typical of digoxin poisoning.

PMID- 21188089
TI  - Hydrogen Sulfide-a potent multichannel anti-arrhythmic drug.
AB  - -Arrhythmia is a big headache for cardiologist for a long time. A new
      antiarrythmic drug with good effects and few side effects should be explored.
      Hydrogen sulfide, a newly found gaseous transmitter, was found to have multi
      effects on a variety of ion channels. It may be a promising antiarrythmic drug.
      This article reviews the different effects of hydrogen sulfide on different ion
      channels.

PMID- 21188088
TI  - The Dual Role of TNF in Pulmonary Edema.
AB  - -Pulmonary edema, a major manifestation of left ventricular heart failure, renal
      insufficiency, shock, diffuse alveolar damage and lung hypersensitivity states,
      is a significant medical problem worldwide and can be life-threatening. The
      proinflammatory cytokine tumor necrosis factor (TNF) has been shown to contribute
      to the pathogenesis and development of pulmonary edema. However, some recent
      studies have demonstrated surprisingly that TNF can also promote alveolar fluid
      reabsorption in vivo and in vitro. This protective effect of the cytokine is
      mediated by the lectin-like domain of the cytokine, which is spatially distinct
      from the TNF receptor binding sites. The TIP peptide, a synthetic mimic of the
      lectin-like domain of TNF, can significantly increase alveolar fluid clearance
      and improve lung compliance in pulmonary edema models. In this review, we will
      discuss the dual role of TNF in pulmonary edema. ABBREVIATIONS: -tumor necrosis
      factor (TNF); acute lung injury (ALI); acute respiratory distress syndrome
      (ARDS); positive end-expiratory pressure (PEEP);epithelial sodium channel
      (ENaC);neural precursor cell-expressed developmentally downregulated (gene 4)
      protein (Nedd4-2);serum and glucocorticoid dependent kinase (Sgk-1);insulin-like
      growth factor 1 (IGF-1);Protein Kinase C (PKC);reactive oxygen species
      (ROS);myosin light chain (MLC);pneumolysin (PLY);listeriolysin (LLO);interleukin
      (IL);bronchoalveolar lavage fluids (BALF);Bacillus Calmette-Guerin (BCG);TNF
      receptor type 1 (TNFR1); TNF receptor type 2 (TNF-R2);

PMID- 21188090
TI  - Successfully ablated atrioventricular nodal reentrant tachycardia in
      unconventional presentation.
AB  - BACKGROUND: #ENTITYSTARTX02014; Sometime, it's difficult to distinguish the
      electrophysiological mechanism of some tachycardia, and so, influencing the
      efficacy and safety of ablation operation. Therefore, it's helpful to analysis
      some tachycardia in particular mechanism, as in this case. METHODS AND RESULTS:
      #ENTITYSTARTX02014; A 49 years old Chinese male patient had a history of
      paroxysmal palpitation for 25 years, and recurred more frequently in the month
      before admission. Electrocardiogram (ECG) showed no abnormity under sinus rhythm,
      and showed no specific sign to distinguish its reentrant mechanism when
      tachycardia running. Electrophysiological examination and the result of
      successful ablation showed that the retrograde pathway of its reentry was in slow
      conduction, and from which the reentry started; moreover, after partially
      ablating, the reentry started from antegrade slow conduction. CONCLUSION:
      #ENTITYSTARTX02014; Careful cardiac electrophysiological examination and paying
      more attention to inducing conditions of tachycardia are critical to accurately
      determining the tachycardia mechanism.

PMID- 21188091
TI  - Treatment and Prevention of Osteoarthritis through Exercise and Sports.
AB  - Osteoarthritis (OA) is a degenerative joint disease with a high prevalence among
      older people. To date, the pathogenesis of the disease and the link between
      muscle function and OA is not entirely understood. As there is no known cure for
      OA, current research focuses on prevention and symptomatic treatment of the
      disorder. Recent research has indicated that muscle weakness precedes the onset
      of OA symptoms. Furthermore, several studies show a beneficial effect of land
      based aerobic and strengthening exercises on pain relief and joint function.
      Therefore, current research focuses on the possibility to employ exercise and
      sports in the prevention and treatment of OA.

PMID- 21188092
TI  - Use of granisetron transdermal system in the prevention of chemotherapy-induced
      nausea and vomiting: a review.
AB  - Until now only intravenous and oral formulations of 5HT(3) receptor antagonists
      have been available. Recently a new formulation of a 5HT(3) receptor antagonist,
      transdermal granisetron, has been developed, and approved by the FDA. Three phase
      I studies to evaluate its pharmacokinetic profile have shown that granisetron
      administered by a transdermal delivery system is absorbed by passive diffusion
      and maximal concentration is reached 48 hours after patch application. The patch
      of 52 cm(2), which contains 34.3 mg of granisetron, releases 3.3 mg of the drug
      every day and maintains a stable average plasma concentration of 2.2 ng/mL over 6
      days, similar to levels obtained with 2 mg of oral granisetron, administered
      every day during the same period of time. Two randomized as yet unpublished
      clinical trials (phase II/III) have been conducted to evaluate the antiemetic
      efficacy of transdermal granisetron in chemotherapy-induced nausea and vomiting,
      in patients receiving moderately and highly emetogenic chemotherapy, compared
      with 2 mg of oral granisetron. More than 800 cancer patients were included in the
      trials. The rate of complete control of acute emesis was 49% for the phase II
      trial and 60% for the phase III trial. Neither trial showed a statistically
      significant difference between transdermal and oral granisetron. The control of
      delayed emesis was observed in 46% of patients, and there were no statistically
      significant differences between transdermal and oral granisetron. The most common
      adverse effects in both trials were constipation (<7%) and headache (<1%); there
      were no statistically significant differences between transdermal and oral
      granisetron. These data show that transdermal granisetron is effective and safe
      in controlling acute emesis induced by chemotherapy with both moderate and high
      emetogenic potential. Efficacy and safety of transdermal granisetron are fully
      comparable with that of oral granisetron. More clinical trials using regimens of
      2 or 3 drugs, including dexamethasone and/or aprepitant, are needed to confirm
      the place of transdermal granisetron in the control of chemotherapy-induced
      nausea and vomiting.

PMID- 21188093
TI  - Role of lapatinib in the first-line treatment of patients with metastatic breast
      cancer.
AB  - Lapatinib is a dual tyrosine kinase inhibitor of epidermal growth factor receptor
      (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER2/ErbB2). EGFR and
      HER2 overexpression is associated with aggressive breast cancer with a high risk
      of disease relapse and death. Although lapatinib targets both EGFR and HER2, its
      effects on HER2 appear to be more critical. The role of lapatinib in the first
      line setting remains unclear. A phase II first-line monotherapy lapatinib trial
      in HER2-therapy-naive metastatic breast cancer (MBC) patients confirms efficacy
      in HER2-positive tumors. Retrospective analysis of a phase III, first-line MBC
      study confirmed incremental benefit from lapatinib and paclitaxel over paclitaxel
      alone in HER2-positive disease. A prospective phase III study confirms
      superiority of letrozole and lapatinib over letrozole alone in HER2-positive MBC.
      Further investigation is required to define the potential first-line role for
      lapatinib. Particular strengths appear to be its manageable toxicity profile,
      lack of cross resistance with trastuzumab, activity in central nervous system
      disease, and synergy in combination with other anticancer therapy. Current
      limitations are lack of dosing recommendations from early trials, lack of
      predictive biomarkers beyond HER2 status, and lack of large prospective phase III
      trials for HER2-positive disease in the first-line setting. The role of lapatinib
      in HER2-negative disease is unclear.

PMID- 21188094
TI  - Optimal management of cancer anorexia-cachexia syndrome.
AB  - According to a recent consensus, cachexia is a complex metabolic syndrome
      associated with underlying illness and characterized by loss of muscle with or
      without loss of fat mass. The prominent clinical feature of cachexia is weight
      loss. Cachexia occurs in the majority of cancer patients before death and it is
      responsible for the deaths of 22% of cancer patients. Although bodyweight is the
      most important endpoint of any cachexia treatment, body composition, physical
      performance and quality of life should be monitored. From the results presented
      here, one can speculate that a single therapy may not be completely successful in
      the treatment of cachexia. From this point of view, treatments involving
      different combinations are more likely to be successful. The objectives of any
      therapeutic combination are two-fold: an anticatabolic aim directed towards both
      fat and muscle catabolism and an anabolic objective leading to the synthesis of
      macromolecules such as contractile proteins.

PMID- 21188095
TI  - Evaluation of degarelix in the management of prostate cancer.
AB  - Medical castration using gonadotropin-releasing hormone (GnRH) receptor agonists
      currently provides the mainstay of androgen deprivation therapy for prostate
      cancer. Although effective, these agents only reduce testosterone levels after a
      delay of 14 to 21 days; they also cause an initial surge in testosterone that can
      stimulate the cancer and lead to exacerbation of symptoms ("clinical flare") in
      patients with advanced disease. Phase III trial data for the recently approved
      GnRH receptor blocker, degarelix, demonstrated that it is as effective and well
      tolerated as GnRH agonists. However, it has a pharmacological profile more
      closely matching orchiectomy, with an immediate onset of action and faster
      testosterone and PSA suppression, without a testosterone surge or microsurges
      following repeated injections. As a consequence, with this GnRH blocker, there is
      no risk of clinical flare and no need for concomitant antiandrogen flare
      protection. Degarelix therefore provides a useful addition to the hormonal
      armamentarium for prostate cancer and offers a valuable new treatment option for
      patients with hormone-sensitive advanced disease. Here, we review key preclinical
      and clinical data for degarelix, and look at patient-focused perspectives in the
      management of prostate cancer.

PMID- 21188096
TI  - Role of denileukin diftitox in the treatment of persistent or recurrent cutaneous
      T-cell lymphoma.
AB  - Denileukin diftitox (Ontak((r))) is indicated for the treatment of patients with
      persistent or recurrent cutaneous T-cell lymphoma (CTCL), a rare
      lymphoproliferative disorder of the skin. Denileukin diftitox was the first
      fusion protein toxin approved for the treatment of a human disease. This fusion
      protein toxin combines the IL2 protein with diphtheria toxin, and targets the
      CD25 subunit of the IL2 receptor, resulting in the unique delivery of a cytocidal
      agent to CD-25 bearing T-cells. Historically, immunotherapy targeting malignant T
      cells including monoclonal antibodies has been largely ineffective as cytocidal
      agents compared to immunotherapy directed against B-cells such as rituximab. This
      review will summarize the development of denileukin diftitox, its proposed
      mechanism of action, the pivotal clinical trials that led to its FDA approval,
      the improvements in quality of life, and the common toxicities experienced during
      the treatment of patients with CTCL. CTCL is often a chronic progressive lymphoma
      requiring the sequential use of treatments such as retinoids, traditional
      chemotherapy, or biological response modifiers. The incorporation of the
      immunotoxin denileukin diftitox into the sequential or combinatorial treatment of
      CTCL will also be addressed.

PMID- 21188097
TI  - Everolimus - a new approach in the treatment of renal cell carcinoma.
AB  - With the increasing understanding of the biology of the disease and the
      development of targeted therapy, there has been a paradigm shift in the treatment
      of clear cell metastatic renal cell carcinoma (mRCC). Traditionally patients with
      metastatic RCC have been treated with immunotherapy which has limited efficacy.
      The multikinase inhibitors sunitinib, sorafenib and pazopanib, the VEGF antibody
      bevacizumab in combination with interferon and the mTOR inhibitor temsirolimus
      have all been shown to prolong progression-free survival in phase III studies.
      Here we review another mTOR inhibitor, everolimus (Afinitor((r)); Novartis, USA)
      which was approved in March 2009 by the US FDA for treatment of targeted-therapy
      refractory metastatic renal cell cancer. The phase III study of everolimus (the
      RECORD study) was terminated early after a significant difference in efficacy was
      noted in the treatment arm with everolimus (progression-free survival of 4.0
      months in patients on the treatment arm vs 1.9 months in the placebo arm). The
      most common adverse events were stomatitis, pneumonitis, fatigue and infections.
      We review Phase I-III data with a particular emphasis on safety data and patient
      focused outcomes.

PMID- 21188098
TI  - Rituximab for the treatment of patients with chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder that
      originates from antigen-experienced B lymphocytes that do not die and hence
      accumulate due to external survival signals or undergo apoptosis and are
      replenished by proliferating precursors. These neoplastic lymphocytes exhibit a
      characteristic immunophenotype of CD5(+)/CD19(+)/CD20(+)/HLA-DR+/CD23(+)/sIgdim.
      Thus, the CD20 antigen has been an appealing target for therapy. The introduction
      of the monoclonal antibody rituximab (anti-CD20) enabled an outstanding advance
      in CLL treatment. The introduction of this monoclonal antibody into chemotherapy
      regimens has dramatically improved complete response rates and progression-free
      survival in patients with both untreated and relapsed CLL. Although only
      preliminary data from phase III confirmatory trials have been reported, the FCR
      regimen, which combines fludarabine and cyclophosphamide with rituximab, is
      currently the most effective treatment regimen for CLL patients, and has also
      been demonstrated to significantly improve overall survival. The success of
      rituximab and the identification of other CLL lymphocyte surface antigens have
      spurred the development of a multitude of monoclonal antibodies targeting
      distinct proteins and epitopes in an attempt to target CLL cells more
      effectively.

PMID- 21188099
TI  - Metastatic clear cell carcinoma of the kidney: therapeutic role of bevacizumab.
AB  - The biology and pathogenesis of clear cell carcinoma of the kidney has been
      extensively investgated, and the role of von Hipple-Landau gene inactivation and
      tumor associated angiogenesis is now recognized. Development of vascular
      endothelial growth factor inhibitors and phase 3 clinical trials utilizing this
      class of agents has produced a new treatment paradigm for patients with
      metastatic renal cell carcinoma (RCC). One of the active regimens identified is
      the combination of bevacizumab and interferon-alpha. Recently published reports
      provided evidence of the clinical and biologic activity of this therapy. The
      current manuscript reviews the background and rationale for the activity of
      bevacizumab in RCC, and results from recent clinical trials with this agent alone
      or in combination with targeted agents or cytokines. The role of this therapy in
      contrast to other targeted agents is reviewed, and the potential utility as well
      as questions raised by recent studies are discussed.

PMID- 21188100
TI  - Role of bevacizumab therapy in the management of glioblastoma.
AB  - Glioblastoma is one of the most common primary brain tumors and one of the most
      difficult to treat. In population-based studies only 30% of patients will survive
      1 year and in the most efficacious surgery, irradiation, and chemotherapy
      clinical trials approximately 20% will live 2 years. Bevacizumab is a
      recombinant, antivascular epidermal growth factor receptor (VEGF) monoclonal
      antibody with 6 VEGF-binding residues that binds to VEGF, preventing VEGF from
      binding to its target, VEGFR-1 and VEGFR-2, on endothelial cells. Through its
      binding to VEGF ligands bevacizumab reduces tumor angiogenesis and vasogenic
      brain edema; the consequences are that bevacizumab reduces the rate of
      glioblastoma tumor growth and its associated tumoral edema, thereby improving
      quality of life and survival for patients suffering from cerebral glioblastoma.
      In this review, we will summarize the studies that led to the use of bevacizumab
      in glioblastoma and the potential side-effects and complications that can be
      associated with its use and, finally, new opportunities for drug combinations
      with bevacizumab.

PMID- 21188101
TI  - Global cancer research initiative.
AB  - Cancer is an increasing problem for low- and middle-income countries undergoing
      an epidemiologic transition from dominantly acute communicable disease to more
      frequent chronic disease with increased public health successes in the former
      domain. Progress against cancer in high-income countries has been modest and has
      come at enormous expense. There are several well-conceived global policy and
      planning initiatives which, with adequate political will, can favorably impact
      the growing global cancer challenges. Most financial resources for cancer,
      however, are spent on diagnosis and management of patients with disease in
      circumstances where specific knowledge about effective approaches is
      significantly limited, and the majority of interventions, other than surgery, are
      not cost-effective in resource-limited countries by global standards. In summary,
      how to intervene effectively on a global scale for the majority of citizens who
      develop cancer is poorly defined. In contrast to technology-transfer approaches,
      markedly increased clinical research activities are more likely to benefit cancer
      sufferers. In these contexts, a global cancer research initiative is proposed,
      and mechanisms for realizing such an effort are suggested.

PMID- 21188102
TI  - Identification of a novel prostate cancer biomarker, caveolin-1: Implications and
      potential clinical benefit.
AB  - While prostate cancer is a common disease in men, it is uncommonly life
      threatening. To better understand this phenomenon, tumor biologists have sought
      to elucidate the mechanisms that contribute to the development of virulent
      prostate cancer. The recent discovery that caveolin-1 (Cav-1) functions as an
      important oncogene involved in prostate cancer progression reflects the success
      of this effort. Cav-1 is a major structural coat protein of caveolae, specialized
      plasma membrane invaginations involved in multiple cellular functions, including
      molecular transport, cell adhesion, and signal transduction. Cav-1 is aberrantly
      overexpressed in human prostate cancer, with higher levels evident in metastatic
      versus primary sites. Intracellular Cav-1 promotes cell survival through
      activation of Akt and enhancement of additional growth factor pro-survival
      pathways. Cav-1 is also secreted as a biologically active molecule that promotes
      cell survival and angiogenesis within the tumor microenvironment. Secreted Cav-1
      can be reproducibly detected in peripheral blood using a sensitive and specific
      immunoassay. Cav-1 levels distinguish men with prostate cancer from normal
      controls, and preoperative Cav-1 levels predict which patients are at highest
      risk for relapse following radical prostatectomy for localized disease. Thus,
      secreted Cav-1 is a promising biomarker in identifying clinically significant
      prostate cancer.

PMID- 21188103
TI  - Management of metastatic renal cell carcinoma in patients with poor prognosis.
AB  - An improved understanding of renal cell carcinoma (RCC) biology has translated
      into major advances in the treatment of patients with metastatic RCC in recent
      years. Clinical and pathologic criteria can be used to identify RCC patients with
      poor prognoses. Such patients, however, are often excluded from the cancer
      clinical trials that guide treatment recommendations. This article reviews
      available information on the management of patients with metastatic RCC and poor
      risk features, focusing on the role of vascular endothelial growth factor (VEGF)
      pathway and mammalian target of rapamycin (mTOR) inhibitors. While patients with
      poor risk features have a more guarded outcome, treatment with temsirolimus has
      produced meaningful improvements in overall survival for this population.
      Definitive phase III trial data are lacking for the VEGF pathway inhibitors in
      patients with poor prognostic features. However, available data suggest that such
      patients tolerate VEGF pathway blockade reasonably well and are likely to achieve
      some benefit relative to treatment with interferon. Ongoing translational
      research efforts may help to define novel treatment approaches specific for
      patients with metastatic RCC and poor prognostic features.

PMID- 21188104
TI  - A pilot study assessing social support among cancer patients enrolled on clinical
      trials: a comparison of younger versus older adults.
AB  - PURPOSE: This study tested the logistical feasibility of obtaining data on social
      support systems from cancer patients enrolled on clinical trials and compared the
      social support of older adults (age >=65) and younger adults (<50 years of age)
      with cancer. METHODS: Patients had to be eligible for a phase II or phase III
      oncology clinical trial and enter the study prior to treatment. Patients filled
      out the Lubben Social Network Scale (LSNS) at baseline. The Symptom Distress
      Scale (SDS) and single-item overall quality of life (QOL) Uniscale were assessed
      at baseline and weekly for 4 weeks. RESULTS: There was no significant difference
      in overall mean Lubben social support levels by age. Older patients had more
      relatives they felt close to (85% versus 53% with 5 or more relatives, P = 0.02),
      heard from more friends monthly (84% versus 53% with 3 or more friends, P =
      0.02), less overall symptom distress (P = 0.03), less insomnia (P = 0.003),
      better concentration (P = 0.005), better outlook (P = 0.01), and less depression
      (P = 0.005) than younger patients. CONCLUSIONS: Younger subjects reported worse
      symptoms, a smaller social support network, and fewer close friends and relatives
      than older subjects. Having someone to discuss decisions and seeing friends or
      relatives often was associated with longer survival.

PMID- 21188106
TI  - Cancer prevention, aerobic capacity, and physical functioning in survivors
      related to physical activity: a recent review.
AB  - According to recent published reports, over 12 million new cases of cancer were
      estimated worldwide for 2007. Estimates from 2008 predict that cancer will
      account for 22.8% of all deaths in the US. Another report stated 50% to 75% of
      cancer deaths in the US are related to smoking, poor dietary choices, and
      physical inactivity. A 2004 report indicated obesity and/or a sedentary lifestyle
      increases the risk of developing several types of cancer. Conversely, several
      large-scale cohort studies point to the positive relationship between physical
      activity and a reduction in cancer risk. In addition, research over the last few
      years has clearly shown cardiorespiratory benefits, increases in quality of life
      (QOL), and increases in physical functioning for cancer survivors who engage in
      exercise programs. Thus, the purpose of this review is to highlight three areas
      related to cancer and physical activity. First, information concerning the
      prevention of cancer through physical activity is addressed. Second, recent
      studies identifying changes in volume of oxygen uptake (VO(2)) and/or
      cardiorespiratory functioning involving exercise with cancer survivors is
      presented. Third, studies identifying changes in cancer survivors' physical
      functional capacity and QOL are presented. Finally, a summary of the review is
      offered.

PMID- 21188105
TI  - Role of erlotinib in first-line and maintenance treatment of advanced non-small
      cell lung cancer.
AB  - Erlotinib hydrochloride (Tarceva((r))) is a member of a class of small molecule
      inhibitors that targets the tyrosine kinase domain of the epidermal growth factor
      receptor (EGFR), with anti-tumor activity in preclinical models. Erlotinib
      represents a new-generation of agents known as "targeted therapies" designed to
      act upon cancer cells by interfering with aberrant specific activated pathways
      needed for tumor growth, angiogenesis and cell survival. Since its approval in
      November 2004 for the treatment of locally advanced or metastatic non-small cell
      lung cancer (NSCLC) after the failure of at least one prior chemotherapy regimen
      and with a view to improving patients' outcomes and prevent symptoms, the
      scientific community has evaluated the potential role of erlotinib in other
      scenarios such as in maintenance therapy and, in first-line setting for a
      selected population based on biological markers of response such as mutations of
      the EGFR. The convenient once-a-day pill administration and the good toxicity
      profile of erlotinib make it a reasonable candidate for testing in this context.
      This report provides a review of the role of erlotinib therapy in advanced NSCLC.
      It summarizes current data and perspectives of erlotinib in upfront treatment and
      maintenance for advanced NSCLC as well as looking at candidate biomarkers of
      response to these new targeted-agents.

PMID- 21188107
TI  - Cetuximab in the treatment of head and neck cancer: preliminary results outside
      clinical trials.
AB  - INTRODUCTION: The purpose of this study was to evaluate the clinical efficacy in
      our daily practice, outside clinical trials, of cetuximab plus radiotherapy in a
      majority of treatment-naive patients with locoregionally advanced head and neck
      squamous cell carcinomas. METHODS: A retrospective study was performed to
      evaluate outcomes in patients who were treated definitively with cetuximab and
      radiotherapy (ExRT). Patients with stage III or IV, nonmetastatic, measurable
      squamous cell carcinoma of the head and neck (SCCHN) were eligible. RESULTS:
      There were 18 males and two females. The median age was 61 years (range from 49
      to 87 years old). Concurrent radiotherapy and cetuximab was used, in first line,
      in 17 patients with locally advanced disease; two patients with recurrent SCCHN,
      who were intolerant of Cisplatin-based regimens, were treated with radiotherapy
      combined with weekly cetuximab; and 1 patient received cetuximab and radiotherapy
      postoperatively. The median time of response was 10 months (range from 2 to 24
      months). A partial response was observed in 11 cases; a complete response in nine
      cases. The occurrence of grade 2-3 skin toxicity was observed in 11 cases. Skin
      toxicity was clearly correlated with a better response and the duration of the
      response to the treatment. The use of cetuximab in combination with radiotherapy
      does not increase the side effects of radiotherapy. At the end of the follow-up,
      17 patients died. CONCLUSION: Cetuximab, with its highly targeted mechanism of
      action and synergistic activity with current treatment modalities, is a valuable
      treatment option in head and neck patients. The effect of the epidermal growth
      factor receptor antagonist occurs without any change in the pattern and the
      severity of toxicity usually associated with head and neck radiation. Cetuximab
      seems not to provide the most benefit for patients with oropharyngeal cancers but
      will in patients with T4 tumors. However, the median duration of local control
      was less as described in the clinical trials.

PMID- 21188108
TI  - Ixabepilone development across the breast cancer continuum: a paradigm shift.
AB  - The epothilone analog ixabepilone exhibits reduced susceptibility to several
      important tumor survival mechanisms that limit the efficacy of taxanes and
      anthracyclines. As a single agent, ixabepilone has shown promise in metastatic
      breast cancer when anthracyclines, taxanes, or capecitabine have failed; and in
      early-stage breast cancer that is taxane-naive or has previously received taxanes
      in the adjuvant or metastatic setting. Compared with capecitabine alone,
      ixabepilone used in combination with capecitabine in patients previously treated
      with and resistant to anthracyclines and taxanes produced a 25% reduction in the
      risk of disease progression. Triple-negative tumors showed particular
      susceptibility to this doublet. Ixabepilone has also demonstrated efficacy as
      first-line therapy in combination with targeted agents such as bevacizumab and
      trastuzumab. Ongoing investigations should provide insight as to how this agent
      could be integrated into treatment of early-stage disease. In clinical studies,
      toxicities with ixabepilone were manageable and reversible through dose reduction
      or delay, even in patients with extensive or heavily-pretreated disease. Thus,
      ixabepilone represents a useful addition to the therapeutic options available for
      advanced breast cancer, and it may extend progression-free survival in patients
      with limited treatment options.

PMID- 21188110
TI  - Efficacy and safety of amrubicin hydrochloride for treatment of relapsed small
      cell lung cancer.
AB  - Long-term survival is quite uncommon in refractory small cell lung cancer (SCLC)
      patients, with less than 25% of patients with limited-stage disease and 1%-2% of
      patients with extensive-stage disease remaining alive at five years. Recent
      clinical studies have demonstrated the promising efficacy of amrubicin for
      patients with relapsed SCLC. This review presents the results of clinical studies
      showing the efficacy and safety of amrubicin for the treatment of relapsed SCLC.
      Amrubicin is a synthetic anthracycline agent with a similar structure to
      doxorubicin, in which the hydroxyl group at position 9 in amrubicin is replaced
      by an amino group to enhance efficacy. It is converted to an active metabolite,
      amrubicinol, which is 5-54 times more active than amrubicin. Amrubicin and
      amrubicinol are inhibitors of DNA topoisomerase II, exerting their cytotoxic
      effects by stabilizing a topoisomerase II-mediated cleavable complex. The
      toxicity of amrubicin is similar to that of doxorubicin, although amrubicin shows
      almost no cardiotoxicity. In the relevant trials, amrubicin was administered
      intravenously at a dose of 35-40 mg/m(2) on days 1-3 every three weeks. The
      response rate was 34%-52% and median survival times were 8.1-12.0 months. Common
      hematologic toxicities included neutropenia, leucopenia, anemia,
      thrombocytopenia, and febrile neutropenia. Nonhematologic adverse events included
      Grade 3-4 anorexia, asthenia, hyponatremia, and nausea. The results of the
      studies which demonstrated the efficacy of monotherapy for relapsed SCLC involved
      mainly Japanese patients. Therefore, it is necessary to conduct more clinical
      studies in non-Japanese patients to confirm the efficacy of amrubicin.

PMID- 21188109
TI  - Temsirolimus in the treatment of relapsed and/or refractory mantle cell lymphoma.
AB  - Patients with mantle cell lymphoma (MCL) have a poor prognosis; consequently, new
      therapeutic approaches, such as rapamycin and its derivates, mammalian target of
      rapamycin (mTOR) inhibitors, are warranted. Temsirolimus (also known as CCI-779),
      a dihydroester of rapamycin, in MCL cell lines inhibited mTOR, downregulated p21
      and v-Raf, and induced autophagy. The first clinical trial in MCL patients was
      performed using 250 mg of temsirolimus weekly for 6-12 cycles. The overall
      response rate was 38%; the median time to progression was 6.5 months, median
      overall survival was 12 months, and the median duration of response was 6.9
      months. At lower dose (25 mg/week), the overall response rate was 41%, median
      overall survival was 14 months, and time to progression was 6 months. In another
      trial, 162 patients were randomly assigned to receive temsirolimus at 2 different
      doses (175 mg/week for 3 weeks, then 75 mg or 25 mg/week) or a treatment chosen
      by the investigator among the most frequently adopted single agents for treatment
      of relapsed MCL. Patients treated with 175/75 mg of temsirolimus had
      significantly higher response rates and longer progression-free survival than
      those treated with investigator's choice therapy. These data support the use of
      mTOR inhibitors for the treatment of MCL, probably in combination with other
      agents, such as antiangiogenic drugs or histone acetylase inhibitors.

PMID- 21188112
TI  - Positive response to neoadjuvant cyclophosphamide and doxorubicin in
      topoisomerase II nonamplified/HER2/neu negative/polysomy 17 absent breast cancer
      patients.
AB  - PURPOSE: Human epidermal growth factor receptor 2 (HER2)/neu, topoisomerase II
      alpha (TOP2A), and polysomy 17 may predict tumor responsiveness to doxorubicin
      (DOX) therapy. METHODS: We identified neoadjuvant DOX/cyclophosphamide treated
      breast cancer patients in our registry from 1997 to 2008 with sufficient tissue
      for testing (n = 34). Fluorescence in situ hybridization (FISH) testing was done
      on deparaffinized tissue sections pretreated using vendor's standard protocol
      modification, and incubated with US Food and Drug Administration approved Abbott
      Diagnostics Vysis PathVysionTM probe set, including Spectrum-Green-conjugated
      probe to alpha-satellite DNA located at the centromere of chromosome 17 (17p11.1
      q11.1) and a Spectrum-Orange-conjugated probe to the TOP2A gene. Morphometric
      analysis was performed using a MetaSystems image analysis system. Manual counting
      was performed on all samples in which autofluorescence and/or artifact prevented
      the counting of sufficient numbers of cells. A ratio >2.0 was considered positive
      for TOP2A amplification. Polysomy 17 (PS17) presence was defined as signals of
      >=2.5. Outcomes were pathological complete response (pCR), partial response (PR),
      and nonresponse (NR). RESULTS: Of 34 patients tested, one was TOP2A amplified
      (hormone receptor negative/HER2 negative, partial responder). The subset of TOP2A
      nonamplified, HER2 negative, and PS17 absent (n = 23) patients had treatment
      response: pCR = 2 (9%), PR = 14 (61%), and NR = 7 (30%). Including the two PS17
      present and HER2-positive patients (n = 33), 76% of TOP2A nonamplified patients
      had pCR or PR. CONCLUSIONS: We observed substantial treatment response in
      patients lacking three postulated predictors that would be difficult to attribute
      to cyclophosphamide alone. Patients who are HER2 negative and lack TOP2A
      amplification and PS17 should not be excluded from receiving DOX-containing
      regimens.

PMID- 21188111
TI  - Treatment of cutaneous melanoma: current approaches and future prospects.
AB  - Melanoma is the most aggressive and deadly type of skin cancer. Surgical
      resection with or without lymph node sampling is the standard of care for primary
      cutaneous melanoma. Adjuvant therapy decisions may be informed by careful
      consideration of prognostic factors. High-dose adjuvant interferon alpha-2b
      increases disease-free survival and may modestly improve overall survival. Less
      toxic alternatives for adjuvant therapy are currently under study. External beam
      radiation therapy is an option for nodal beds where the risk of local recurrence
      is very high. In-transit melanoma metastases may be treated locally with surgery,
      immunotherapy, radiation, or heated limb perfusion. For metastatic melanoma, the
      options include chemotherapy or immunotherapy; targeted anti-BRAF and anti-KIT
      therapy is under active investigation. Standard chemotherapy yields objective
      tumor responses in approximately 10%-20% of patients, and sustained remissions
      are uncommon. Immunotherapy with high-dose interleukin-2 yields objective tumor
      responses in a minority of patients; however, some of these responses may be
      durable. Identification of activating mutations of BRAF, NRAS, c-KIT, and GNAQ in
      distinct clinical subtypes of melanoma suggest that these are molecularly
      distinct. Emerging data from clinical trials suggest that substantial
      improvements in the standard of care for melanoma may be possible.

PMID- 21188113
TI  - Frequency of heterozygous TET2 deletions in myeloproliferative neoplasms.
AB  - The Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs),
      including polycythemia vera, essential thrombocythemia, and primary
      myelofibrosis, are a group of clonal hematopoietic stem cell disorders with
      overlapping clinical and cytogenetic features and a variable tendency to evolve
      into acute leukemia. These diseases not only share overlapping chromosomal
      abnormalities but also a number of acquired somatic mutations. Recently,
      mutations in a putative tumor suppressor gene, ten-eleven translocation 2 (TET2)
      on chromosome 4q24 have been identified in 12% of patients with MPN. Additionally
      4q24 chromosomal rearrangements in MPN, including TET2 deletions, have also been
      observed using conventional cytogenetics. The goal of this study was to
      investigate the frequency of genomic TET2 rearrangements in MPN using
      fluorescence in situ hybridization as a more sensitive method for screening and
      identifying genomic deletions. Among 146 MPN patients, we identified two patients
      (1.4%) who showed a common 4q24 deletion, including TET2. Our observations also
      indicated that the frequency of TET2 deletion is increased in patients with an
      abnormal karyotype (5%).

PMID- 21188114
TI  - Role of intranasal fentanyl in breakthrough pain management in cancer patients.
AB  - Fentanyl is a strong opioid analgesic, which is commonly used in the form of a
      transdermal patch for the treatment of chronic cancer pain. An intranasal route
      of fentanyl administration is a novel treatment for breakthrough cancer pain
      (BTCP). The prevalence, assessment, and management of BTCP is outlined in this
      paper, and basic pharmacodynamic and pharmacokinetic properties, dosing
      guidelines, and clinical experience with the use of intranasal fentanyl in this
      indication are discussed. Intranasal fentanyl is an attractive and convenient
      mode of BTCP treatment in opioid-tolerant patients due to its quick onset and
      short duration of action, noninvasive administration route, high bioavailability,
      and avoidance of a hepatic first-pass effect. Until now, few clinical trials have
      been conducted with intranasal fentanyl, but all have confirmed its usefulness
      and acceptability in BTCP treatment. Intranasal fentanyl may be used in opioid
      tolerant patients without nasal pathologies. The dose should be titrated in each
      patient regardless of the regular opioid dose administered. Future studies should
      compare intranasal fentanyl with other fentanyl formulations used for BTCP
      management, and with analgesia, adverse effects, and quality of life taken into
      consideration.

PMID- 21188115
TI  - New developments in treatment of ovarian carcinoma: focus on trabectedin.
AB  - Trabectedin is a new marine-derived compound that binds the DNA minor groove and
      interacts with proteins of the DNA repair machinery. Trabectedin has shown
      promising single-agent activity in pretreated patients with soft tissue sarcoma,
      and ovarian and breast cancer, and combination with various other
      chemotherapeutic drugs seems feasible. Toxicities are mainly hematologic and
      hepatic, with Grade 3-4 neutropenia and thrombocytopenia observed in
      approximately 50% and 20% of patients, respectively, and Grade 3-4 elevation of
      liver enzymes observed in 35%-50% of patients treated with trabectedin. The
      recently reported results of a large Phase III trial comparing pegylated
      liposomal doxorubicin (PLD) alone with a combination of PLD and trabectedin in
      patients with recurrent ovarian cancer showed improved progression-free survival
      with the combination of trabectedin and PLD, albeit at the price of increased
      toxicity. Current research focuses on the identification of predictive factors
      for patients treated with trabectedin, as well as the development of other
      combinations.

PMID- 21188116
TI  - Radiotherapy combined with hormonal therapy in prostate cancer: the state of the
      art.
AB  - Androgen-deprivation therapy (ADT) is used routinely in combination with
      definitive external beam radiation therapy (EBRT) in patients with high-risk
      clinically localized or locally advanced disease. The combined treatment (ADT
      EBRT) also seems to play a significant role in improving treatment results in the
      intermediate-risk group of prostate cancer patients. On the other hand, there is
      a growing body of evidence that treatment with ADT can be associated with serious
      and lifelong adverse events including osteoporosis, cardiovascular disease,
      diabetes, and many others. Almost all ADT adverse events are time dependant and
      tend to increase in severity with prolongation of hormonal manipulation.
      Therefore, it is crucial to clearly state the optimal schedule for ADT in
      combination with EBRT, that maintaining the positive effect on treatment efficacy
      would keep the adverse events risk at reasonable level. To achieve this goal,
      treatment schedule may have to be highly individualized on the basis of the
      patient-specific potential vulnerability to adverse events. In this study, the
      concise and evidence-based review of current literature concerning the general
      rationales for combining radiotherapy and hormonal therapy, its mechanism,
      treatment results, and toxicity profile is presented.

PMID- 21188118
TI  - FACE: the barefaced facts of AI potency.
AB  - The use of third-generation aromatase inhibitors (AIs), such as anastrozole and
      letrozole, as initial adjuvant hormonal therapy in postmenopausal women (PMW)
      with hormone receptor-positive (HR+) breast cancer offers a significant benefit
      over tamoxifen for reducing recurrence risk. Clinical studies, including the
      Arimidex Tamoxifen Alone or in Combination (ATAC) and the Breast International
      Group (BIG) 1-98 trials, have proven that both anastrozole and letrozole are,
      respectively, superior to tamoxifen in improving disease-free survival. Although
      differing in design, objectives, and follow-up time, these trials offer some
      insight into the comparative clinical efficacy of these two nonsteroidal AIs. In
      particular, results from BIG 1-98 show that letrozole significantly reduces early
      distant metastatic (DM) events, which constitute the majority of early recurrence
      events. Subsequently, there is a beneficial overall survival effect emerging in
      the trial, whereas survival is unchanged with anastrozole after 100 months of
      follow-up in ATAC. Significant differences in the potency of these two drugs, vis
      a-vis their degree of aromatase inhibition, have been observed in comparative
      trials and show that letrozole causes a more complete suppression of estrogen
      levels than does anastrozole. Whether this difference in potency is relevant to
      reductions in DM events during adjuvant therapy remains unclear. The Femara
      Anastrozole Clinical Evaluation trial is addressing this issue in a more
      unequivocal manner by comparing initial adjuvant treatment with anastrozole or
      letrozole in a population of breast cancer patients at high risk of recurrence:
      PMW with HR+ disease and axillary lymph node involvement.

PMID- 21188117
TI  - Epigenomics in cancer management.
AB  - The identification of all epigenetic modifications implicated in gene expression
      is the next step for a better understanding of human biology in both normal and
      pathological states. This field is referred to as epigenomics, and it is defined
      as epigenetic changes (ie, DNA methylation, histone modifications and regulation
      by noncoding RNAs such as microRNAs) on a genomic scale rather than a single
      gene. Epigenetics modulate the structure of the chromatin, thereby affecting the
      transcription of genes in the genome. Different studies have already identified
      changes in epigenetic modifications in a few genes in specific pathways in
      cancers. Based on these epigenetic changes, drugs against different types of
      tumors were developed, which mainly target epimutations in the genome. Examples
      include DNA methylation inhibitors, histone modification inhibitors, and small
      molecules that target chromatin-remodeling proteins. However, these drugs are not
      specific, and side effects are a major problem; therefore, new DNA sequencing
      technologies combined with epigenomic tools have the potential to identify novel
      biomarkers and better molecular targets to treat cancers. The purpose of this
      review is to discuss current and emerging epigenomic tools and to address how
      these new technologies may impact the future of cancer management.

PMID- 21188119
TI  - The potential carcinogenic risk of tanning beds: clinical guidelines and patient
      safety advice.
AB  - INTRODUCTION: In 2009, the WHO listed ultraviolet (UV) radiation as a group 1
      carcinogen. In spite of this, each year, millions of people tan indoor in Western
      countries. The aim of this review is to summarize evidence of tanning bed
      carcinogenesis and to present guidelines for use of tanning beds and patient
      safety advice. METHODS: A narrative review of the literature was conducted based
      on both PubMed and Medline searches and on literature review of the retrieved
      papers. RESULTS: Use of indoor tanning beds represents a significant and
      avoidable risk factor for the development of both melanoma and nonmelanoma skin
      cancers. Frequent tanners are more often adolescent females. Tanning beds have
      additional potential adverse effects such as burns, solar skin damage, infection,
      and possibly also addictive behavior. DISCUSSION: The effort in preventing UV
      light-induced carcinogenesis should currently be aimed at developing new
      strategies for public health information. Tanning beds are one preventable source
      of UV radiation. In the majority of people solar UV radiation continues to be the
      major factor and therefore anti-tanning campaigns must always include sunbathers.

PMID- 21188120
TI  - Review of catumaxomab in the treatment of malignant ascites.
AB  - Malignant ascites is frequently found with various solid tumors, and no
      established treatment options exist, apart from symptomatic paracentesis.
      Catumaxomab, a trifunctional bispecific monoclonal antibody, has two binding
      specificities directed to epithelial cell adhesion molecule (EpCAM) and the T
      cell antigen CD3. With its Fc-fragment, catumaxomab additionally binds accessory
      cells, including dendritic cells, macrophages, and natural killer cells. The
      trifunctional approach thus leads to a major histocompatibility complex
      unrestricted but specific killing of epithelial tumor cells without need for
      preactivation or external costimulation. Because EpCAM is expressed in most solid
      tumors, but not in tissue of mesothelial origin, intraperitoneal treatment with
      catumaxomab is tumor-specific. Intraperitoneal treatment with catumaxomab
      resulted in a significant prolongation of puncture-free survival in patients with
      malignant ascites due to epithelial cancer. Catumaxomab has been approved in
      Europe for the intraperitoneal treatment of malignant ascites in patients with
      EpCAM-positive epithelial tumors where standard therapy is not available or no
      longer feasible.

PMID- 21188121
TI  - Results of a phase I pilot clinical trial examining the effect of plant-derived
      resveratrol and grape powder on Wnt pathway target gene expression in colonic
      mucosa and colon cancer.
AB  - CONTEXT: Resveratrol exhibits colon cancer prevention activity in animal models;
      it is purported to have this activity in humans and inhibit a key signaling
      pathway involved in colon cancer initiation, the Wnt pathway, in vitro. DESIGN: A
      phase I pilot study in patients with colon cancer was performed to evaluate the
      effects of a low dose of plant-derived resveratrol formulation and resveratrol
      containing freeze-dried grape powder (GP) on Wnt signaling in the colon. Eight
      patients were enrolled and normal colonic mucosa and colon cancer tissue were
      evaluated by Wnt pathway-specific microarray and quantitative real-time
      polymerase chain reaction (qRT-PCR) pre- and post-exposure to resveratrol/GP.
      RESULTS: Based on the expression of a panel of Wnt target genes, resveratrol/GP
      did not inhibit the Wnt pathway in colon cancer but had significant (p < 0.03)
      activity in inhibiting Wnt target gene expression in normal colonic mucosa. The
      greatest effect on Wnt target gene expression was seen following ingestion of 80
      g of GP per day (p < 0.001). These results were confirmed with qRT-PCR of
      cyclinD1 and axinII. The inhibitory effect of GP on Wnt signal throughput was
      confirmed in vitro with a normal colonic mucosa-derived cell line. CONCLUSIONS:
      These data suggest that GP, which contains low dosages of resveratrol in
      combination with other bioactive components, can inhibit the Wnt pathway in vivo
      and that this effect is confined to the normal colonic mucosa. Further study of
      dietary supplementation with resveratrol-containing foods such as whole grapes or
      GP as a potential colon cancer preventive strategy is warranted. TRIAL
      REGISTRATION: NCT00256334.

PMID- 21188122
TI  - Validation of the cell cycle G(2) delay assay in assessing ionizing radiation
      sensitivity and breast cancer risk.
AB  - Genetic variations in cell cycle checkpoints and DNA repair genes are associated
      with prolonged cell cycle G(2) delay following ionizing radiation (IR) treatment
      and breast cancer risk. However, different studies reported conflicting results
      examining the association between post-IR cell cycle delay and breast cancer risk
      utilizing four different parameters: cell cycle G(2) delay index, %G(2)-M,
      G(2)/G(0)-G(1), and (G(2)/G(0)-G(1))/S. Therefore, we evaluated whether different
      parameters may influence study results using a data set from 118 breast cancer
      cases and 225 controls as well as lymphoblastoid and breast cancer cell lines
      with different genetic defects. Our results suggest that cell cycle G(2) delay
      index may serve as the best parameter in assessing breast cancer risk, genetic
      regulation of IR-sensitivity, and mutations of ataxia telangiectasia mutated
      (ATM) and TP53. Cell cycle delay in 21 lymphoblastoid cell lines derived from
      BRCA1 mutation carriers was not different from that in controls. We also showed
      that IR-induced DNA-damage signaling, as measured by phosphorylation of H2AX on
      serine 139 (gamma-H2AX) was inversely associated with cell cycle G(2) delay
      index. In summary, the cellular responses to IR are extremely complex; mutations
      or genetic variations in DNA damage signaling, cell cycle checkpoints, and DNA
      repair contribute to cell cycle G(2) delay and breast cancer risk. The cell cycle
      G(2) delay assay characterized in this study may help identify subpopulations
      with elevated risk of breast cancer or susceptibility to adverse effects in
      normal tissue following radiotherapy.

PMID- 21188123
TI  - Patient-derived acute myeloid leukemia (AML) bone marrow cells display distinct
      intracellular kinase phosphorylation patterns.
AB  - Multiparametric analyses of phospho-protein activation in patients with acute
      myeloid leukemia (AML) offers a quantitative measure to monitor the activity of
      novel intracellular kinase (IK) inhibitors. As recent clinical investigation with
      FMS-like tyrosine-3 inhibitors demonstrated, targeting IK with selective
      inhibitors can have a modest clinical benefit. Because multiple IKs are active in
      patients with AML, multikinase inhibitors may provide the necessary inhibition
      profile to achieve a more sustained clinical benefit. We here describe a method
      of assessing the activation of several IKs by flow cytometry. In 40 different
      samples of patients with AML we observed hyper-activated phospho-proteins at
      baseline, which is modestly increased by adding stem cell factor to AML cells.
      Finally, AML cells had a significantly different phospho-protein profile compared
      with cells of the lymphocyte gate. In conclusion, our method offers a way to
      determine the activation status of multiple kinases in AML and hence is a
      reliable assay to evaluate the pharmacodynamic activity of novel multikinase
      inhibitors.

PMID- 21188124
TI  - Is social support associated with improved clinical outcomes in geriatric lung
      cancer patients? Observations from North Central Cancer Treatment Group Studies
      N9921 and N0222.
AB  - BACKGROUND: Social support is defined as a network of family/friends who provide
      practical and emotional help. A sizable literature describes a direct
      relationship between social support and improved cancer clinical outcomes. This
      study explored the extent of social support and its potential association with
      survival and adverse events in geriatric lung cancer patients. METHODS: One
      hundred thirteen patients, who were aged 65 years or older, had incurable cancer,
      and were enrolled in one of two chemotherapy trials, completed the Lubben Social
      Network Scale, a validated instrument that measures social support. All were
      followed for survival and chemotherapy-related adverse events. RESULTS: The
      median age (range) of the cohort was 74 years (65-91), and performance scores of
      0, 1, or 2 were observed in 29%, 55%, and 16%, respectively. Forty-two percent
      were women. This cohort had a high level of social support: 81% reported they
      "always" had someone to take them to medical appointments. However, there were no
      gender-based differences in social support and no associations between social
      support and either survival or adverse events. CONCLUSION: In this cohort of
      geriatric lung cancer patients - all of whom were treated during a clinical trial
      - there was a high level of social support. However, there were no gender-based
      differences in extent of social support, and the latter did not predict clinical
      outcomes.

PMID- 21188125
TI  - Ixabepilone: a new treatment option for the management of taxane-resistant
      metastatic breast cancer.
AB  - Ixabepilone (Ixempra((r)); Bristol-Myers Squibb) is a novel microtubule
      stabilizing agent recently approved for the treatment of metastatic breast cancer
      (MBC). This article focuses on considerations for ixabepilone administration and
      adverse event (AE) management, drawing from the biomedical literature indexed in
      PubMed, published abstracts from the American Society of Clinical Oncology annual
      meetings, and the manufacturer's prescribing information for ixabepilone.
      Administered as monotherapy or in combination with capecitabine in clinical
      studies, ixabepilone demonstrated positive clinical response rates, prolonged
      progression-free survival, and a favorable safety profile in patients with MBC.
      Treatment-related AEs were predictable and manageable with dose modification,
      treatment interruption, and active management. As ixabepilone undergoes
      development in earlier lines of breast cancer therapy and in other solid tumors,
      oncology nurses will encounter more and more patients receiving ixabepilone
      therapy. If nurses are acquainted with the unique management strategies
      associated with ixabepilone treatment, as detailed herein, patients are more
      likely to receive the full benefit of therapy.

PMID- 21188126
TI  - Evolving role of cetuximab in the treatment of colorectal cancer.
AB  - In recent years, the monoclonal epidermal growth factor receptor (EGFR)-targeting
      antibody cetuximab was introduced into systemic therapy of colorectal cancer and
      gained an established role in the treatment of this disease. Cetuximab was shown
      to be active as a single agent in chemorefractory metastatic disease as well as
      in combination with varying chemotherapies. Recently, randomized trials
      demonstrated the activity of cetuximab combinations in the first-line setting of
      metastatic colorectal cancer. Interestingly, the activity of cetuximab was
      restricted to patients with KRAS wildtype tumors, as was seen with panitumumab,
      another EGFR antibody. While 60%-70% of tumors harbor KRAS wildtype genes, 30%
      40% of tumors express oncogenic KRAS with mutations in codons 12 and 13 causing
      constitutive activation of signaling cascades downstream of EGFR and resistance
      to EGFR blockade. Since proof of KRAS wildtype status became a prerequisite for
      cetuximab treatment, KRAS testing is being established throughout the world.
      Future trials will address the question which part of the KRAS wildtype cohort
      will benefit from EGFR inhibition and how to identify those patients.
      Additionally, new strategies for treatment of KRAS mutated tumors are strongly
      needed. Recent developments and future strategies will be summarized.

PMID- 21188127
TI  - Prevention of acute chemotherapy-induced nausea and vomiting: the role of
      palonosetron.
AB  - Prevention of nausea and vomiting is the main goal of antiemetic treatment in
      cancer patients scheduled to receive chemotherapy. To prevent acute emesis,
      antiemetics should be administered just before chemotherapy and patients should
      be protected for up to 24 hours after chemotherapy initiation. The emetogenic
      potential of chemotherapeutic agents guides clinicians towards the most
      appropriate antiemetic prophylaxis. Current guidelines recommend the use of 5
      HT(3) receptor antagonist (RA) either alone or in combination with dexamethasone
      and/or a neurokinin-1 RA both in the acute and delayed phases. The second
      generation 5-HT(3)RA palonosetron exhibits a longer half-life and a higher
      binding affinity than older antagonists. Palonosetron has been approved by the
      FDA for the prevention of chemotherapy-induced nausea and vomiting (CINV) in
      patients scheduled to receive either moderately (MEC) or highly emetogenic
      chemotherapy (HEC) and for the prevention of delayed CINV in patients receiving
      MEC. The present review will discuss the role of palonosetron in the prevention
      of acute CINV.

PMID- 21188128
TI  - Update on the management of prostate cancer with goserelin acetate: patient
      perspectives.
AB  - The guidelines for the use of androgen deprivation therapy (ADT) have changed
      significantly over the last 5 years. This paper reviews the current
      recommendations and documents the reasons for these changes, in a review of the
      world's literature on ADT over the last 5 years. Special emphasis on randomized
      controlled trials and high-impact journals was included in the Medline search and
      review. One hundred articles on this topic written in the last 5 years were
      reviewed. Fifty-nine contained nonindustry-biased findings in major-impact
      journals and were available in English. The benefits of ADT are evident in
      several areas, including neoadjuvantly and adjuvantly in patients treated with
      external beam radiation therapy for intermediate- and high-risk disease; in
      patients who have undergone prostatectomy and who are found to have lymph node
      involvement on surgical resection; in high-risk patients after definitive
      therapy; and in patients who have developed symptomatic local progression or
      metastasis. This paper reviews the risks and benefits in each of these scenarios
      and the risks of androgen deprivation in general, and delineates the areas where
      ADT was previously recommended, but has been found to no longer be of benefit.

PMID- 21188129
TI  - Bortezomib in the management of multiple myeloma.
AB  - Multiple myeloma (MM) is a B-cell malignancy characterized by clonal expansion of
      plasma cells within the bone marrow, the presence of a serum and/or urine
      monoclonal protein, lytic bone lesions, and anemia. On a cellular level, the
      disease is characterized by complex interactions between tumor cells and the
      surrounding bone marrow microenvironment. Understanding of the relationship
      between malignant plasma cells and the microenvironment has sparked ongoing
      efforts to develop targeted therapeutic agents for treatment of this disease. The
      successful development of the first-in-class small-molecule proteasome inhibitor
      bortezomib occurred as a result of these efforts. This review focuses on the
      rationale for bortezomib therapy in the treatment of patients with newly
      diagnosed and relapsed MM, important treatment-related side effects, and future
      directions for use of bortezomib and other, emerging proteasome inhibitors.

PMID- 21188131
TI  - Review of Y-ibritumomab tiuxetan as first-line consolidation radio-immunotherapy
      for B-cell follicular non-Hodgkin's lymphoma.
AB  - Several studies have indicated that radioimmunotherapy is an effective and
      clinically relevant complementary therapeutic approach for patients with B-cell
      non-Hodgkin's lymphoma (NHL) and may convert partial to complete response when
      given as consolidation after induction chemotherapy. Yttrium-90((90)Y)
      ibritumomab tiuxetan ((90)Y-IT, Zevalin((r)), Y2B8) has documented efficacy for
      both indolent and aggressive NHL. Patients considered eligible for (90)Y-IT
      treatment should satisfy several screening criteria. A recently completed
      randomized study for patients with follicular lymphoma has demonstrated that
      (90)Y-ibritumomab consolidation also produced a marked prolongation of the median
      time to progression from 13.5 to 37 months, while partial responders seem to
      derive relatively more benefit. Other published and ongoing studies explore a
      similar use for patients with aggressive lymphoma. Studies are comparing the use
      of (90)Y-IT consolidation with the anti-CD20 antibody rituximab maintenance,
      which is also gaining acceptance. In conclusion, the documented benefit of
      radioimmunotherapy should be viewed in the context of the goals of treatment and
      the changing standards of care for lymphoma.

PMID- 21188130
TI  - The role of azacitidine in the management of myelodysplastic syndromes (MDS).
AB  - Myelodysplastic syndromes (MDS) are a group of common bone marrow disorders
      characterized by ineffective hematopoiesis, peripheral cytopenias, and a
      propensity for transformation to acute myeloid leukemia (AML). For many years,
      the main treatment option for MDS was best supportive care which alleviates
      symptoms but has no effect on the natural course of the disease. The recent
      approval of the demethylating agent azacitidine represents a significant advance
      in the treatment of MDS. The results of two randomized trials with azacitidine
      have shown an overall response rate between 40% and 60%, an improved quality of
      life, a reduced risk of transformation to AML and a definite survival advantage
      compared to best supportive care or low-dose chemotherapy. Current data on
      azacitidine and its place in the treatment of MDS are reviewed.

PMID- 21188132
TI  - Critical appraisal of temozolomide formulations in the treatment of primary brain
      tumors: patient considerations.
AB  - Chemotherapy is assuming an increasingly important role in the treatment of
      malignant gliomas, of which temozolomide (TMZ) is a key part. TMZ belongs to a
      class of second-generation imidazotetrazinone prodrugs that exhibit linear
      pharmacokinetics and do not require hepatic metabolism for activation to the
      active metabolite. New intravenous (iv) TMZ formulations have recently been
      approved based on studies of bioequivalence between iv and oral TMZ. The efficacy
      of TMZ was initially evaluated in patients with recurrent disease but phase II
      and III trials in newly diagnosed gliomas are available. The results of a large
      phase III trial that compared RT alone vs RT concomitant with oral TMZ created a
      new standard of adjuvant treatment. Efficacy data for iv TMZ on which its
      approval was based are those extrapolated from clinical trials with oral TMZ. No
      comparative data are available on the differences in tolerability and patient
      satisfaction between oral and iv formulations of TMZ, or for quality of life. New
      oral formulations could encourage the adherence of patients to treatment.
      Although patients presumably would prefer oral treatment, iv formulations may be
      an alternative in noncompliant patients or patients for whom good adherence could
      not be expected.

PMID- 21188133
TI  - Role of EGF inhibitors in the treatment of recurrent or metastatic squamous cell
      head and neck cancer.
AB  - Squamous cell cancer of the head and neck (SCCHN) is a major contributor to
      morbidity and mortality worldwide. In recent years, inhibition of the epidermal
      growth factor receptor has become an established treatment strategy in SCCHN both
      in the up-front treatment and in the recurrent and metastatic setting. This
      review summarizes the most important developments of the recent past and provides
      an overview of newer developments.

PMID- 21188134
TI  - The role of bendamustine in the treatment of indolent non-Hodgkin lymphoma.
AB  - There is no consensus on recommendations for the treatment of relapsed and
      refractory indolent non-Hodgkin lymphoma (NHL). Bendamustine hydrochloride
      (bendamustine) has recently been approved for treatment of these patients.
      Bendamustine is a uniquely structured alkylating agent that lacks cross
      resistance with other alkylators. This agent has a high degree of activity
      against a variety of tumor cell lines. Clinically, bendamustine has demonstrated
      activity against indolent NHL, chronic lymphocytic lymphoma, multiple myeloma and
      mantle cell lymphoma. Moreover, studies have validated its activity in patients
      with indolent NHL who are resistant to purine analogs and rituximab. The
      cytotoxic activity of bendamustine has been shown to be synergistic with
      rituximab in hematological malignancies. The incidence of alopecia is
      significantly less than with other alkylating agents. Myelosuppression is the
      major toxicity associated with bendamustine.

PMID- 21188135
TI  - Palonosetron for the prevention of chemotherapy-induced nausea and vomiting:
      approval and efficacy.
AB  - Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant
      deterioration in quality of life. The emetogenicity of the chemotherapeutic
      agents, repeated chemotherapy cycles, and patient characteristics (female gender,
      younger age, low alcohol consumption, history of motion sickness) are the major
      risk factors for CINV. This review provides a detailed description of
      palonosetron, a second-generation 5-hydroxytryptamine 3 (5-HT(3)) receptor
      antagonist. The chemistry and pharmacology of palonosetron are described, as well
      as the initial and recent clinical trials. Palonosetron has a longer half-life
      and a higher binding affinity than the first-generation 5-HT(3) receptor
      antagonists. Palonosetron has been approved for the prevention of acute CINV in
      patients receiving either moderately or highly emetogenic chemotherapy and for
      the prevention of delayed CINV in patients receiving moderately emetogenic
      chemotherapy. In recent studies, compared to the first-generation 5-HT(3)
      receptor antagonists, palonosetron in combination with dexamethasone demonstrated
      better control of delayed CINV in patients receiving highly emetogenic
      chemotherapy. There were no clinically relevant adverse reactions reported in the
      palonosetron clinical trials which were different from the common reactions
      reported for the 5-HT(3) receptor antagonist class. Due to its efficacy in
      controlling both acute and delayed CINV, palonosetron may be very effective in
      the clinical setting of multiple-day chemotherapy and bone marrow
      transplantation.

PMID- 21188136
TI  - Distinct effects of contraction agonists on the phosphorylation state of cofilin
      in pulmonary artery smooth muscle.
AB  - We hypothesized that agonist-induced contraction correlates with the phospho
      cofilin/cofilin (P-CF/CF) ratio in pulmonary artery (PA) rings and cultured
      smooth muscle cells (PASMCs). PA rings were used for isometric contractions and
      along with PASMCs for assay of P-CF/CF by isoelectric focusing and
      immunoblotting. The P-CF/CF measured 22.5% in PA and differentiated PASMCs, but
      only 14.8% in undifferentiated PASMCs. With comparable contraction responses in
      PA, endothelin-1 (100 nM) and norepinephrine (1 MUM) induced a 2-fold increase of
      P-CF/CF, while angiotensin II (1 MUM) induced none. All agonists activated Rho
      kinase and LIMK2, and activation was eliminated by inhibition of Rho-kinase.
      Microcystin LF (20 nM) potentiated the angiotensin II, but not the 5
      hydroxytryptamine (1 MUM)-mediated increase of P-CF/CF. In conclusion, all tested
      agonists activate the Rho-kinase-LIMK pathway and increase P-CF/CF. Angiotensin
      II activates PP2A and counteracts the LIMK-mediated CF phosphorylation. CF
      phosphorylation stabilizes peripheral actin structures and may contribute to the
      maximal contraction of PA.

PMID- 21188137
TI  - BCR-ABL mutation testing to predict response to tyrosine kinase inhibitors in
      patients with chronic myeloid leukemia.
AB  - Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic
      myeloid leukemia (CML). Although randomized evidence demonstrates that imatinib
      (a commercially available TKI) prolongs event-free survival in patients with CML,
      some patients develop imatinib intolerance or resistance. In addition, imatinib
      is less effective in patients who have progressed to more advanced disease
      stages, such as accelerated phase and blastic phase CML. For these reasons, 2nd
      generation TKIs that can inhibit the BCR-ABL protein more effectively or target
      additional disease mechanisms have been developed. Two such drugs have also been
      approved for clinical use by the FDA, nilotinib and dasatinib. Resistance to TKI
      treatment is thought to be mediated through various mechanisms, the most common
      of which is BCR-ABL1 mutations. Testing for mutations in BCR-ABL1 may predict
      lack of response to imatinib or may inform the choice between alternative TKIs.

PMID- 21188138
TI  - Aromatase is a direct target of FOXL2: C134W in granulosa cell tumors via a
      single highly conserved binding site in the ovarian specific promoter.
AB  - BACKGROUND: Granulosa cell tumors (GCT) of the ovary often express aromatase and
      synthesize estrogen, which in turn may influence their progression. Recently a
      specific point mutation (C134W) in the FOXL2 protein was identified in >94% of
      adult-type GCT and it is likely to contribute to their development. A number of
      genes are known to be regulated by FOXL2, including aromatase/CYP19A1, but it is
      unclear which are direct targets and whether the C134W mutation alters their
      regulation. Recently, it has been reported that FOXL2 forms a complex with
      steroidogenic factor 1 (SF-1) which is a known regulator of aromatase in
      granulosa cells. METHODOLOGY/PRINCIPAL FINDINGS: In this work, the human GCT
      derived cell lines KGN and COV434 were heterozygous and wildtype for the
      FOXL2:C134W mutation, respectively. KGN had abundant FOXL2 mRNA expression but it
      was not expressed in COV434. Expression of exogenous FOXL2:C134W in COV434 cells
      induced higher expression of a luciferase reporter for the ovarian specific
      aromatase promoter, promoter II (PII) (-516bp) than expression of wildtype FOXL2,
      but did not alter induction of a similar reporter for the steroidogenic acute
      regulatory protein (StAR) promoter (-1300bp). Co-immunoprecipitation confirmed
      that FOXL2 bound SF-1 and that it also bound its homologue, liver receptor
      homologue 1 (LRH-1), however, the C134W mutation did not alter these interactions
      or induce a selective binding of the proteins. A highly conserved putative
      binding site for FOXL2 was identified in PII. FOXL2 was demonstrated to bind the
      site by electrophoretic mobility shift assays (EMSA) and site-directed
      mutagenesis of this element blocked its differential induction by wildtype FOXL2
      and FOXL2:C134W. CONCLUSIONS/SIGNIFICANCE: These findings suggest that aromatase
      is a direct target of FOXL2:C134W in adult-type GCT via a single distinctive and
      highly conserved binding site in PII and therefore provide insight into the
      pathogenic mechanism of this mutation.

PMID- 21188140
TI  - Dominating clasp of the financial sector revealed by partial correlation analysis
      of the stock market.
AB  - What are the dominant stocks which drive the correlations present among stocks
      traded in a stock market? Can a correlation analysis provide an answer to this
      question? In the past, correlation based networks have been proposed as a tool to
      uncover the underlying backbone of the market. Correlation based networks
      represent the stocks and their relationships, which are then investigated using
      different network theory methodologies. Here we introduce a new concept to tackle
      the above question--the partial correlation network. Partial correlation is a
      measure of how the correlation between two variables, e.g., stock returns, is
      affected by a third variable. By using it we define a proxy of stock influence,
      which is then used to construct partial correlation networks. The empirical part
      of this study is performed on a specific financial system, namely the set of 300
      highly capitalized stocks traded at the New York Stock Exchange, in the time
      period 2001-2003. By constructing the partial correlation network, unlike the
      case of standard correlation based networks, we find that stocks belonging to the
      financial sector and, in particular, to the investment services sub-sector, are
      the most influential stocks affecting the correlation profile of the system.
      Using a moving window analysis, we find that the strong influence of the
      financial stocks is conserved across time for the investigated trading period.
      Our findings shed a new light on the underlying mechanisms and driving forces
      controlling the correlation profile observed in a financial market.

PMID- 21188141
TI  - Gene regulatory networks from multifactorial perturbations using Graphical Lasso:
      application to the DREAM4 challenge.
AB  - A major challenge in the field of systems biology consists of predicting gene
      regulatory networks based on different training data. Within the DREAM4
      initiative, we took part in the multifactorial sub-challenge that aimed to
      predict gene regulatory networks of size 100 from training data consisting of
      steady-state levels obtained after applying multifactorial perturbations to the
      original in silico network. Due to the static character of the challenge data, we
      tackled the problem via a sparse Gaussian Markov Random Field, which relates
      network topology with the covariance inverse generated by the gene measurements.
      As for the computations, we used the Graphical Lasso algorithm which provided a
      large range of candidate network topologies. The main task was to select the
      optimal network topology and for that, different model selection criteria were
      explored. The selected networks were compared with the golden standards and the
      results ranked using the scoring metrics applied in the challenge, giving a
      better insight in our submission and the way to improve it.Our approach provides
      an easy statistical and computational framework to infer gene regulatory networks
      that is suitable for large networks, even if the number of the observations
      (perturbations) is greater than the number of variables (genes).

PMID- 21188139
TI  - The effect of DNA-dependent protein kinase on adeno-associated virus replication.
AB  - BACKGROUND: DNA-dependent protein kinase (DNA-PK) is a DNA repair enzyme and
      plays an important role in determining the molecular fate of the rAAV genome.
      However, the effect this cellular enzyme on rAAV DNA replication remains elusive.
      METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we characterized the roles
      of DNA-PK on recombinant adeno-associated virus DNA replication. Inhibition of
      DNA-PK by a DNA-PK inhibitor or siRNA targeting DNA-PKcs significantly decreased
      replication of AAV in MO59K and 293 cells. Southern blot analysis showed that
      replicated rAAV DNA formed head-to-head or tail-to-tail junctions. The head-to
      tail junction was low or undetectable suggesting AAV-ITR self-priming is the
      major mechanism for rAAV DNA replication. In an in vitro replication assay, anti
      Ku80 antibody strongly inhibited rAAV replication, while anti-Ku70 antibody
      moderately decreased rAAV replication. Similarly, when Ku heterodimer (Ku70/80)
      was depleted, less replicated rAAV DNA were detected. Finally, we showed that AAV
      ITRs directly interacted with Ku proteins. CONCLUSION/SIGNIFICANCE: Collectively,
      our results showed that that DNA-PK enhances rAAV replication through the
      interaction of Ku proteins and AAV-ITRs.

PMID- 21188142
TI  - Syntaxin 5 is required for copper homeostasis in Drosophila and mammals.
AB  - Copper is essential for aerobic life, but many aspects of its cellular uptake and
      distribution remain to be fully elucidated. A genome-wide screen for copper
      homeostasis genes in Drosophila melanogaster identified the SNARE gene Syntaxin 5
      (Syx5) as playing an important role in copper regulation; flies heterozygous for
      a null mutation in Syx5 display increased tolerance to high dietary copper. The
      phenotype is shown here to be due to a decrease in copper accumulation, a
      mechanism also observed in both Drosophila and human cell lines. Studies in adult
      Drosophila tissue suggest that very low levels of Syx5 result in neuronal defects
      and lethality, and increased levels also generate neuronal defects. In contrast,
      mild suppression generates a phenotype typical of copper-deficiency in viable,
      fertile flies and is exacerbated by co-suppression of the copper uptake gene
      Ctr1A. Reduced copper uptake appears to be due to reduced levels at the plasma
      membrane of the copper uptake transporter, Ctr1. Thus Syx5 plays an essential
      role in copper homeostasis and is a candidate gene for copper-related disease in
      humans.

PMID- 21188143
TI  - Comparative genomics suggests that the fungal pathogen pneumocystis is an
      obligate parasite scavenging amino acids from its host's lungs.
AB  - Pneumocystis jirovecii is a fungus causing severe pneumonia in immuno-compromised
      patients. Progress in understanding its pathogenicity and epidemiology has been
      hampered by the lack of a long-term in vitro culture method. Obligate parasitism
      of this pathogen has been suggested on the basis of various features but remains
      controversial. We analysed the 7.0 Mb draft genome sequence of the closely
      related species Pneumocystis carinii infecting rats, which is a well established
      experimental model of the disease. We predicted 8'085 (redundant) peptides and
      14.9% of them were mapped onto the KEGG biochemical pathways. The proteome of the
      closely related yeast Schizosaccharomyces pombe was used as a control for the
      annotation procedure (4'974 genes, 14.1% mapped). About two thirds of the mapped
      peptides of each organism (65.7% and 73.2%, respectively) corresponded to crucial
      enzymes for the basal metabolism and standard cellular processes. However, the
      proportion of P. carinii genes relative to those of S. pombe was significantly
      smaller for the "amino acid metabolism" category of pathways than for all other
      categories taken together (40 versus 114 against 278 versus 427, P<0.002).
      Importantly, we identified in P. carinii only 2 enzymes specifically dedicated to
      the synthesis of the 20 standard amino acids. By contrast all the 54 enzymes
      dedicated to this synthesis reported in the KEGG atlas for S. pombe were detected
      upon reannotation of S. pombe proteome (2 versus 54 against 278 versus 427,
      P<0.0001). This finding strongly suggests that species of the genus Pneumocystis
      are scavenging amino acids from their host's lung environment. Consequently, they
      would have no form able to live independently from another organism, and these
      parasites would be obligate in addition to being opportunistic. These findings
      have implications for the management of patients susceptible to P. jirovecii
      infection given that the only source of infection would be other humans.

PMID- 21188144
TI  - Consequences of daily administered parathyroid hormone on myeloma growth, bone
      disease, and molecular profiling of whole myelomatous bone.
AB  - BACKGROUND: Induction of osteolytic bone lesions in multiple myeloma is caused by
      an uncoupling of osteoclastic bone resorption and osteoblastic bone formation.
      Current management of myeloma bone disease is limited to the use of
      antiresorptive agents such as bisphosphonates. METHODOLOGY/PRINCIPAL FINDINGS: We
      tested the effects of daily administered parathyroid hormone (PTH) on bone
      disease and myeloma growth, and we investigated molecular mechanisms by analyzing
      gene expression profiles of unique myeloma cell lines and primary myeloma cells
      engrafted in SCID-rab and SCID-hu mouse models. PTH resulted in increased bone
      mineral density of myelomatous bones and reduced tumor burden, which reflected
      the dependence of primary myeloma cells on the bone marrow microenvironment.
      Treatment with PTH also increased bone mineral density of uninvolved murine bones
      in myelomatous hosts and bone mineral density of implanted human bones in
      nonmyelomatous hosts. In myelomatous bone, PTH markedly increased the number of
      osteoblasts and bone-formation parameters, and the number of osteoclasts was
      unaffected or moderately reduced. Pretreatment with PTH before injecting myeloma
      cells increased bone mineral density of the implanted bone and delayed tumor
      progression. Human global gene expression profiling of myelomatous bones from
      SCID-hu mice treated with PTH or saline revealed activation of multiple distinct
      pathways involved in bone formation and coupling; involvement of Wnt signaling
      was prominent. Treatment with PTH also downregulated markers typically expressed
      by osteoclasts and myeloma cells, and altered expression of genes that control
      oxidative stress and inflammation. PTH receptors were not expressed by myeloma
      cells, and PTH had no effect on myeloma cell growth in vitro.
      CONCLUSIONS/SIGNIFICANCE: We conclude that PTH-induced bone formation in
      myelomatous bones is mediated by activation of multiple signaling pathways
      involved in osteoblastogenesis and attenuated bone resorption and myeloma growth;
      mechanisms involve increased osteoblast production of anti-myeloma factors and
      minimized myeloma induction of inflammatory conditions.

PMID- 21188145
TI  - Natural variation in Arabidopsis thaliana revealed a genetic network controlling
      germination under salt stress.
AB  - Plant responses to environmental stresses are polygenic and complex traits. In
      this study quantitative genetics using natural variation in Arabidopsis thaliana
      was used to investigate the genetic architecture of plant responses to salt
      stress. Eighty seven A. thaliana accessions were screened and showed a large
      variation for root development and seed germination under 125 and 200 mM NaCl,
      respectively. Twenty two quantitative trait loci for these traits have been
      detected by phenotyping two recombinants inbred line populations, Sha x Col and
      Sha x Ler. Four QTLs controlling germination under salt were detected in the Sha
      x Col population. Interestingly, only one allelic combination at these four QTLs
      inhibits germination under salt stress, implying strong epistatic interactions
      between them. In this interacting context, we confirmed the effect of one QTL by
      phenotyping selected heterozygous inbred families. We also showed that this QTL
      is involved in the control of germination under other stress conditions such as
      KCl, mannitol, cold, glucose and ABA. Our data highlights the presence of a
      genetic network which consists of four interacting QTLs and controls germination
      under limiting environmental conditions.

PMID- 21188146
TI  - Intestinal damage determines the inflammatory response and early complications in
      patients receiving conditioning for a stem cell transplantation.
AB  - BACKGROUND: Stem cell transplantation (SCT) is still complicated by the
      occurrence of fever and inflammatory complications attributed to neutropenia and
      subsequent infectious complications. The role of mucosal barrier injury (MBI) of
      the intestinal tract therein has received little attention. METHODS: We performed
      a retrospective analysis in 163 SCT recipients of which data had been collected
      prospectively on intestinal damage (citrulline), inflammation (C-reactive
      protein), and neutrophil count. Six different conditioning regimens were studied;
      5 myeloablative (MA) and 1 non-myeloablative (NMA). Linear mixed model
      multivariate and AUC analyses were used to define the role of intestinal damage
      in post-SCT inflammation. We also studied the relationship between the degree of
      intestinal damage and the occurrence of early post-SCT complications. RESULTS: In
      the 5 MA regimen there was a striking pattern of inflammatory response that
      coincided with the occurrence of severe intestinal damage. This contrasted with a
      modest inflammatory response seen in the NMA regimen in which intestinal damage
      was limited. With linear mixed model analysis the degree of intestinal damage was
      shown the most important determinant of the inflammatory response, and both
      neutropenia and bacteremia had only a minor impact. AUC analysis revealed a
      strong correlation between citrulline and CRP (Pearson correlation r = 0.96).
      Intestinal damage was associated with the occurrence of bacteremia and acute lung
      injury, and influenced the kinetics of acute graft-versus-host disease.
      CONCLUSION: The degree of intestinal damage after myeloablative conditioning
      appeared to be the most important determined the inflammatory response following
      SCT, and was associated with inflammatory complications. Studies should explore
      ways to ameliorate cytotoxic therapy-induced intestinal damage in order to reduce
      complications associated with myeloablative conditioning therapy.

PMID- 21188147
TI  - Antibacterial and antiviral roles of a fish beta-defensin expressed both in
      pituitary and testis.
AB  - Defensins are a group of cationic peptides that exhibit broad-spectrum
      antimicrobial activity. In this study, we cloned and characterized a beta
      defensin from pituitary cDNA library of a protogynous hermaphroditic orange
      spotted grouper (Epinephelus coioides). Interestingly, the beta-defensin was
      shown to be dominantly expressed in pituitary and testis by RT-PCR and Western
      blot analysis, and its transcript level is significantly upregulated in
      reproduction organs from intersexual gonad to testis during the natural and
      artificial sex reversal. Promoter sequence and the responsible activity region
      analyses revealed the pituitary-specific POU1F1a transcription binding site and
      testis-specific SRY responsible site, and demonstrated that the pituitary
      specific POU1F1a transcription binding site that locates between -180 and -208 bp
      is the major responsible region of grouper beta-defensin promoter activity.
      Immunofluorescence localization observed its pituicyte expression in pituitary
      and spermatogonic cell expression in testis. Moreover, both in vitro
      antibacterial activity assay of the recombinant beta-defensin and in vivo embryo
      microinjection of the beta-defensin mRNA were shown to be effective in killing
      gram-negative bacteria. And, its antiviral role was also demonstrated in EPC
      cells transfected with the beta-defensin construct. Additionally, the
      antibacterial activity was sensitive to concentrations of Na(+), K(+), Ca(2+) and
      Mg(2+). The above intriguing findings strongly suggest that the fish beta
      defensin might play significant roles in both innate immunity defense and
      reproduction endocrine regulation.

PMID- 21188148
TI  - Minimal gene regulatory circuits for a lysis-lysogeny choice in the presence of
      noise.
AB  - Gene regulatory networks (GRNs) that make reliable decisions should have design
      features to cope with random fluctuations in the levels or activities of
      biological molecules. The phage lambda GRN makes a lysis-lysogeny decision
      informed by the number of phages infecting the cell. To analyse the design of
      decision making GRNs, we generated random in silico GRNs comprised of two or
      three transcriptional regulators and selected those able to perform a lambda-like
      decision in the presence of noise. Various two-protein networks analogous to the
      lambda CI-Cro GRN worked in noise-less conditions but failed when noise was
      introduced. Adding a lambda CII-like protein significantly improved robustness to
      noise. CII relieves the CI-like protein of its 'decider' function, allowing CI to
      be optimized as a decision 'maintainer'. CII's lysogenic decider function was
      improved by its instability and rapid removal once the decision was taken,
      preventing its interference with maintenance. A more reliable decision also
      resulted from simulated co-transcription of the genes for CII and the Cro-like
      protein, which correlates fluctuations in these opposing decider functions and
      makes their ratio less noisy. Thus, the lambda decision network contains design
      features for reducing and resisting noise.

PMID- 21188149
TI  - Disordered microbial communities in the upper respiratory tract of cigarette
      smokers.
AB  - Cigarette smokers have an increased risk of infectious diseases involving the
      respiratory tract. Some effects of smoking on specific respiratory tract bacteria
      have been described, but the consequences for global airway microbial community
      composition have not been determined. Here, we used culture-independent high
      density sequencing to analyze the microbiota from the right and left nasopharynx
      and oropharynx of 29 smoking and 33 nonsmoking healthy asymptomatic adults to
      assess microbial composition and effects of cigarette smoking. Bacterial
      communities were profiled using 454 pyrosequencing of 16S sequence tags (803,391
      total reads), aligned to 16S rRNA databases, and communities compared using the
      UniFrac distance metric. A Random Forest machine-learning algorithm was used to
      predict smoking status and identify taxa that best distinguished between smokers
      and nonsmokers. Community composition was primarily determined by airway site,
      with individuals exhibiting minimal side-of-body or temporal variation. Within
      airway habitats, microbiota from smokers were significantly more diverse than
      nonsmokers and clustered separately. The distributions of several genera were
      systematically altered by smoking in both the oro- and nasopharynx, and there was
      an enrichment of anaerobic lineages associated with periodontal disease in the
      oropharynx. These results indicate that distinct regions of the human upper
      respiratory tract contain characteristic microbial communities that exhibit
      disordered patterns in cigarette smokers, both in individual components and
      global structure, which may contribute to the prevalence of respiratory tract
      complications in this population.

PMID- 21188150
TI  - Modifying the substrate specificity of Carcinoscorpius rotundicauda serine
      protease inhibitor domain 1 to target thrombin.
AB  - Protease inhibitors play a decisive role in maintaining homeostasis and eliciting
      antimicrobial activities. Invertebrates like the horseshoe crab have developed
      unique modalities with serine protease inhibitors to detect and respond to
      microbial and host proteases. Two isoforms of an immunomodulatory two-domain
      Kazal-like serine protease inhibitor, CrSPI-1 and CrSPI-2, have been recently
      identified in the hepatopancreas of the horseshoe crab, Carcinoscorpius
      rotundicauda. Full length and domain 2 of CrSPI-1 display powerful inhibitory
      activities against subtilisin. However, the structure and function of CrSPI-1
      domain-1 (D1) remain unknown. Here, we report the crystal structure of CrSPI-1-D1
      refined up to 2.0 A resolution. Despite the close structural homology of CrSPI-1
      D1 to rhodniin-D1 (a known thrombin inhibitor), the CrSPI-1-D1 does not inhibit
      thrombin. This prompted us to modify the selectivity of CrSPI-1-D1 specifically
      towards thrombin. We illustrate the use of structural information of CrSPI-1-D1
      to modify this domain into a potent thrombin inhibitor with IC(50) of 26.3 nM. In
      addition, these studies demonstrate that, besides the rigid conformation of the
      reactive site loop of the inhibitor, the sequence is the most important
      determinant of the specificity of the inhibitor. This study will lead to the
      significant application to modify a multi-domain inhibitor protein to target
      several proteases.

PMID- 21188151
TI  - Informed consent prior to coronary angiography in a real world scenario: what do
      patients remember?
AB  - BACKGROUND: Patients' informed consent is legally essential before elective
      invasive cardiac angiography (CA) and successive intervention can be done. It is
      unknown to what extent patients can remember previous detailed information given
      by a specially trained doctor in an optimal scenario as compared to standard
      care. METHODOLOGY/PRINCIPAL FINDINGS: In this prospective cohort study 150
      consecutive in-patients and 50 out-patients were included before elective CA was
      initiated. The informed consent was provided and documented in in-patients by
      trained and instructed physicians the day before CA. In contrast, out-patients
      received standard information by different not trained physicians, who did not
      know about this investigation. All patients had to sign a form stating that
      enough information had been given and all questions had been answered
      sufficiently. One hour before CA an assessment of the patients' knowledge about
      CA was performed using a standard point-by-point questionnaire by another
      independent physician. The supplied information was composed of 12 potential
      complications, 3 general, 4 periprocedural and 4 procedural aspects. 95% of the
      patients felt that they had been well and sufficiently informed. Less than half
      of the potential complications could be remembered by the patients and more
      patients could remember less serious than life-threatening complications (27.9+/
      8.8% vs. 47.1+/-11.0%; p<0.001). Even obvious complications like local bleeding
      could not be remembered by 35% of in-patients and 36% of out-patients (p = 0.87).
      Surprisingly, there were only a few knowledge differences between in- and out
      patients. CONCLUSIONS: The knowledge about CA of patients is vague when they give
      their informed consent. Even structured information given by a specially trained
      physician did not increase this knowledge.

PMID- 21188153
TI  - Treatment of noninfectious posterior uveitis with dexamethasone intravitreal
      implant.
AB  - PURPOSE: To report our experience with dexamethasone 0.7 mg sustained-release
      intravitreal implant (Ozurdex((r)); Allergan, Inc, Irvine, CA) in noninfectious
      posterior uveitis. METHODS: A retrospective chart review of patients with
      noninfectious uveitis treated with sustained-release dexamethasone 0.7 mg
      intravitreal implant was performed. Complete ophthalmic examination including
      signs of inflammatory activity, visual acuity, fundus photography, fluorescein
      angiography, optical coherence tomography, and tolerability of the implant were
      assessed. RESULTS: Six eyes of 4 consecutive patients treated with a total of 8
      dexamethasone 0.7 mg sustained-release intravitreal implants for posterior
      noninfectious uveitis were included. Two patients presented with unilateral
      idiopathic posterior uveitis; 2 patients had bilateral posterior uveitis, one
      secondary to sarcoidosis and the other to Vogt-Koyanagi-Harada syndrome. All eyes
      showed clinical and angiographic evidence of decreased inflammation following
      implant placement. Mean follow-up time post-injection was 5.25 months. Four eyes
      received 1 and 2 eyes received 2 Ozurdex implants during the follow-up period.
      The duration of effect of the implant was 3 to 4 months. No serious ocular or
      systemic adverse events were noted during the follow-up period. CONCLUSIONS: In
      patients with noninfectious posterior uveitis, sustained-release dexamethasone
      0.7 mg intravitreal implant may be an effective treatment option for controlling
      intraocular inflammation.

PMID- 21188152
TI  - Eye disorders in patients with multiple sclerosis: natural history and
      management.
AB  - Multiple sclerosis (MS) is a demyelinating disease of the central nervous system
      and leading cause of disability in young adults. Vision impairment is a common
      component of disability for this population of patients. Injury to the optic
      nerve, brainstem, and cerebellum leads to characteristic syndromes affecting both
      the afferent and efferent visual pathways. The objective of this review is to
      summarize the spectrum of eye disorders in patients with MS, their natural
      history, and current strategies for diagnosis and management. We emphasize the
      most common disorders including optic neuritis and internuclear ophthalmoparesis
      and include new techniques, such as optical coherence tomography, which promise
      to better our understanding of MS and its effects on the visual system.

PMID- 21188154
TI  - Detection of retinal changes in Parkinson's disease with spectral-domain optical
      coherence tomography.
AB  - PURPOSE: This pilot study investigated whether high-resolution spectral-domain
      optical coherence tomography (SD-OCT) could detect differences in inner retinal
      layer (IRL), peripapillary retinal nerve fiber layer (RNFL), and macular
      thickness between patients with Parkinson's disease (PD) and controls. METHODS:
      Both eyes of patients with PD and age-matched controls were imaged with the
      Heidelberg Spectralis((r)) HRA + OCT. RNFL, IRL, and macular thickness were
      measured for each eye using Heidelberg software. These measurements were compared
      with validated, published normal values for macular and RNFL thickness, and
      compared with matched controls for IRL thickness. RESULTS: Eighteen eyes from
      nine subjects with PD and 19 eyes of 16 control subjects were evaluated using SD
      OCT. The average age of PD patients was 64 years with a range of 52-75 years. The
      average age of controls was 67 years with a range of 50-81 years. No significant
      reduction in IRL thickness was detected between PD patients and age-matched
      controls at 13 points along a 6 mm horizontal section through the fovea. No
      significant difference in RNFL thickness was detected between PD patients and
      published normal values. Overall average RNFL thickness was 97 MUm for PD
      patients, which exactly matched the normative database value. However,
      significant differences in macular thickness were detected in three of nine
      subfields between PD subjects and published normal values. In PD subjects, the
      outer superior subfield was 2.8% thinner (P = 0.026), while the outer nasal and
      inner inferior subfields were 2.8% (P = 0.016) and 2.7% (P = 0.001) thicker
      compared to published normal values. CONCLUSION: In this pilot study, significant
      differences in macular thickness were detected in three of nine subfields by SD
      OCT. However, SD-OCT did not detect significant reductions in peripapillary RNFL
      and IRL thickness between PD patients and controls. This suggests that macular
      thickness measurements by SD-OCT may potentially be used as an objective,
      noninvasive, and easily quantifiable in vivo biomarker in PD. Larger,
      longitudinal studies are needed to explore these relationships further.

PMID- 21188155
TI  - A randomized, controlled comparison of macroscopic conjunctival hyperemia in
      patients treated with bimatoprost 0.01% or vehicle who were previously controlled
      on latanoprost.
AB  - PURPOSE: To evaluate conjunctival hyperemia associated with bimatoprost 0.01%
      treatment in patients who replace latanoprost 0.005% with bimatoprost 0.01%.
      METHODS: Randomized, double-masked, vehicle-controlled, multicenter study of
      patients with ocular hypertension or glaucoma whose intraocular pressure (IOP)
      was adequately controlled on latanoprost monotherapy. At baseline, patients
      discontinued latanoprost and were randomized to treatment with once-daily
      bimatoprost 0.01% (n = 151) or vehicle (n = 71). The primary endpoint was the
      peak change in macroscopic hyperemia (conjunctival hyperemia evaluated by gross
      visual inspection) from baseline to month 1. RESULTS: Bimatoprost 0.01% was
      noninferior to vehicle in the mean [standard deviation] peak change from baseline
      macroscopic hyperemia at month 1 (0.18 [0.46] in the bimatoprost 0.01% group vs
      0.02 [0.32] in the vehicle group, P = 0.009). The between-group difference was
      0.15 (95% confidence interval [CI]: 0.04, 0.26), which was within the predefined
      margin for noninferiority of 0.5 on a hyperemia grading scale of 0 to +3. There
      were no statistically significant between-group differences in the percentage of
      patients with a >=1-grade increase in macroscopic hyperemia from baseline. Mean
      IOP was decreased from baseline (-0.7 to -1.3 mm Hg) in the bimatoprost 0.01%
      group (P <= 0.002) and was increased from baseline (+3.3 to +3.6 mm Hg) in the
      vehicle group (P < 0.001) at month 1. There were no statistically significant
      between-group differences in adverse events. CONCLUSIONS: Bimatoprost 0.01% was
      noninferior to vehicle with respect to conjunctival hyperemia in this study
      population. Replacement of latanoprost with bimatoprost 0.01% in patients with
      ocular hypertension or glaucoma can result in additional IOP reduction without
      clinically important hyperemia.

PMID- 21188156
TI  - Transcorneal electrical stimulation increases chorioretinal blood flow in normal
      human subjects.
AB  - PURPOSE: The aim of this article is to investigate the effect of transcorneal
      electrical stimulation (TES) on chorioretinal blood flow in healthy human
      subjects. METHODS: The chorioretinal blood flow of 10 healthy subjects was
      measured before and after TES by laser speckle flowgraphy and expressed as the
      square blur rate (SBR). The chorioretinal blood flow was determined before and
      immediately after TES and 0.5, 1, 1.5, 2, 2.5, 3, 24, and 40 h after TES in three
      different areas: the margin of the optic disc, a point located midway between the
      optic disc and macula, and the macula area. The SBR of the stimulated eye is
      expressed relative to the value of the fellow eye. The mean standardized blur
      ratio was calculated as the ratio of the standardized SBR to the baseline SBR.
      The changes of intraocular pressure (IOP), blood pressure (BP), and pulse rate
      (PR) were determined after each measurement of the SBR. The ocular perfusion
      pressure (OPP) was calculated from BP and IOP. RESULTS: The mean standardized
      blur ratio at the optic disc did not change significantly throughout the course
      of the experiment. However, the mean standardized blur ratio midway between the
      optic disc and macula and at the macula area were significantly higher after TES
      than that after sham stimulation at 3 and 24 h (P < 0.05, P < 0.01,
      respectively). At all times, the mean BP, PR, IOP, and OPP were not significantly
      different from the prestimulation values. CONCLUSIONS: TES increases the
      chorioretinal blood flow in normal subjects with minimal effects on the systemic
      blood circulation and the IOP. The increase in chorioretinal blood flow may be
      one of the beneficial effects that TES has on ischemic retinal diseases.

PMID- 21188157
TI  - Aqueous humor penetration of topical bimatoprost 0.01% and bimatoprost 0.03% in
      rabbits.
AB  - PURPOSE: The purpose of this study was to compare the aqueous humor
      concentrations of bimatoprost acid after topical instillation in rabbits of
      bimatoprost ophthalmic solution 0.01% and bimatoprost ophthalmic solution 0.03%,
      two commercially available intraocular pressure-lowering medications. METHODS:
      Male Dutch Belted rabbits were divided into two teratment groups (four
      rabbits/eight eyes per group): bimatoprost 0.01% and bimatoprost 0.03%. Thirty
      microliters (MUL) of study medication was to pically instilled into both eyes of
      each animal. Thirty minutes and 90 minutes after instillation, aqueous humor
      samples were collected. These samples were analyzed by reverse-phase high
      performance liquid chromatography for bimatoprost acid concentration. RESULTS:
      Following a single topical ocular instillation, the bimatoprost 0.01% formulation
      had a lower mean aqueous humor concentration of bimatoprost acid than the
      bimatoprost 0.03% formulation at both 30 minutes (11.5 +/- 2.1 ng/mL versus 37.8
      +/- 28.8 ng/mL; P = 0.17) and 90 minutes (20.8 +/- 5.7 ng/mL versus 45.8 +/- 14.3
      ng/mL; P = 0.03) after topical instillation. CONCLUSIONS: Topical ocular
      instillation of bimatoprost 0.01% produced significantly lower bimatoprost acid
      concentration in the aqueous humor of rabbits than bimatoprost 0.03%, despite the
      4-fold increase of benzalkonium chloride contained in bimatoprost 0.01%.

PMID- 21188158
TI  - Bacterial conjunctivitis.
AB  - CLINICAL QUESTION: What is the best treatment for bacterial conjunctivitis?
      RESULTS: Topical antibiotics expedite recovery from bacterial conjunctivitis. The
      choice of antibiotic usually does not affect outcome. IMPLEMENTATION: Recognition
      of key distinguishing features of bacterial conjunctivitis Pitfalls that can be
      recognized in the history and physical examinationChoice of antibioticWhen to
      refer for specialist treatment.

PMID- 21188159
TI  - Chandelier and interfascicular neurons in the adult mouse piriform cortex.
AB  - The structure of two neuron types native to the adult mouse piriform cortex (PC)
      is described. The first cell, termed an interfascicular neuron (IFN), lies
      between the axon fascicles of layer I. The IFN axon divides dichotomously and
      daughter fibrils run horizontally in the domain of layer Ia. The frequent
      apposition of the IFN axon to distal dendrites of the underlying pyramidal cells
      suggests an en passage synaptic interaction with them. A second neuron observed
      in layer II, or less frequently in layer III, matched in most respects the
      structure of the chandelier cell (CC) described elsewhere in the neo- and archi
      cortex. In the PC, chandelier cells (PC-CC) display the following peculiarities.
      First, the PC-CC axonal field distributes in the neuropil of layers II and III
      and candlesticks are in close apposition to the initial axonal segment of the
      pyramidal cell, although somatic interactions cannot be rule out. Second, the PC
      CC ascending dendrites pierce layer I, receiving short collaterals and boutons en
      passage from the olfactory axons therein. The possible role of IFN's and PC-CC
      and their interactions with the adjacent cells is discussed in the broad context
      of the cellular organization of the PC.

PMID- 21188160
TI  - Primary retroperitoneal paraganglioma simulating a pancreatic mass: a case report
      and review of the literature.
AB  - Paragangliomas are extra-adrenal tumors of the autonomic nervous system and may
      be found within the skull base, neck, chest, and abdomen. When presenting within
      the abdominal cavity, they may arise as a primary retroperitoneal neoplasm and
      can mimic vascular malformations or other conditions related to specific
      retroperitoneal organs such as the pancreas, kidneys, or adrenals.
      Retroperitoneal paragangliomas are mostly benign with good prognosis; however,
      they can present with abdominal pain, palpable mass, or hypertensive episodes.
      Patients should be initially evaluated with catecholamine levels, followed by
      computed tomography or magnetic resonance imaging to locate the primary lesion.
      Surgical excision remains the mainstay of treatment, although advanced disease
      and proximity to vital organs can make excision difficult or impossible. This
      case report describes a patient who initially underwent work up for a suspected
      pancreatic head mass which was discovered to be a retroperitoneal paraganglioma
      by frozen section.

PMID- 21188162
TI  - Age-related differences in auditory processing as assessed by amplitude
      modulation following responses in quiet and in noise.
AB  - Our knowledge of age-related changes in auditory processing in the central
      auditory system is limited, unlike the changes in the peripheral hearing organs
      which are more extensively studied. This study aims to further understanding of
      temporal processing in aging using non-invasive electrophysiological measurements
      in a rat model system. Amplitude modulation following responses (AMFRs) were
      assessed using sinusoidally amplitude modulated (SAM) tones presented to aged (92
      to 95-weeks old) and young (9- to 12-weeks old) Fischer-344 rats. The modulation
      frequency and sound level were systematically varied, and the SAM stimuli were
      also presented simultaneously with wideband background noise at various levels.
      The overall shapes and cutoff frequencies of the AMFR temporal modulation
      transfer functions (tMTFs) were similar between young and aged animals. The fast
      Fourier transform (FFT) amplitudes of the aged animals were similar to the young
      in the 181-512 Hz modulation frequency range, but were significantly lower at
      most modulation frequencies above and below. There were no significant age
      related differences in the nature of growth or FFT amplitudes with change in
      sound level at 256 and 1024 Hz modulation frequencies. The AMFR amplitudes were
      also not correlated with the ABR wave I or wave III amplitudes elicited for
      broadband click stimuli presented at the same sound level suggesting that
      sustained AMFR provide complementary information to phasic ABR responses. The FFT
      amplitudes varied significantly between young and aged animals for SAM stimuli in
      the presence of background noise, depending on the modulation frequency used and
      signal to noise ratio. The results show that the representation of temporally
      modulated stimuli is similar between young and aged animals in quiet listening
      conditions, but diverges substantially with the addition of background noise.
      This is consistent with a decrease in inhibition causing altered temporal
      processing with age.

PMID- 21188163
TI  - Interaction among Skeletal Muscle Metabolic Energy Systems during Intense
      Exercise.
AB  - High-intensity exercise can result in up to a 1,000-fold increase in the rate of
      ATP demand compared to that at rest (Newsholme et al., 1983). To sustain muscle
      contraction, ATP needs to be regenerated at a rate complementary to ATP demand.
      Three energy systems function to replenish ATP in muscle: (1) Phosphagen, (2)
      Glycolytic, and (3) Mitochondrial Respiration. The three systems differ in the
      substrates used, products, maximal rate of ATP regeneration, capacity of ATP
      regeneration, and their associated contributions to fatigue. In this exercise
      context, fatigue is best defined as a decreasing force production during muscle
      contraction despite constant or increasing effort. The replenishment of ATP
      during intense exercise is the result of a coordinated metabolic response in
      which all energy systems contribute to different degrees based on an interaction
      between the intensity and duration of the exercise, and consequently the
      proportional contribution of the different skeletal muscle motor units. Such
      relative contributions also determine to a large extent the involvement of
      specific metabolic and central nervous system events that contribute to fatigue.
      The purpose of this paper is to provide a contemporary explanation of the muscle
      metabolic response to different exercise intensities and durations, with emphasis
      given to recent improvements in understanding and research methodology.

PMID- 21188161
TI  - Postsynaptic signal transduction models for long-term potentiation and
      depression.
AB  - More than a hundred biochemical species, activated by neurotransmitters binding
      to transmembrane receptors, are important in long-term potentiation (LTP) and
      long-term depression (LTD). To investigate which species and interactions are
      critical for synaptic plasticity, many computational postsynaptic signal
      transduction models have been developed. The models range from simple models with
      a single reversible reaction to detailed models with several hundred kinetic
      reactions. In this study, more than a hundred models are reviewed, and their
      features are compared and contrasted so that similarities and differences are
      more readily apparent. The models are classified according to the type of
      synaptic plasticity that is modeled (LTP or LTD) and whether they include
      diffusion or electrophysiological phenomena. Other characteristics that
      discriminate the models include the phase of synaptic plasticity modeled
      (induction, expression, or maintenance) and the simulation method used
      (deterministic or stochastic). We find that models are becoming increasingly
      sophisticated, by including stochastic properties, integrating with
      electrophysiological properties of entire neurons, or incorporating diffusion of
      signaling molecules. Simpler models continue to be developed because they are
      computationally efficient and allow theoretical analysis. The more complex models
      permit investigation of mechanisms underlying specific properties and
      experimental verification of model predictions. Nonetheless, it is difficult to
      fully comprehend the evolution of these models because (1) several models are not
      described in detail in the publications, (2) only a few models are provided in
      existing model databases, and (3) comparison to previous models is lacking. We
      conclude that the value of these models for understanding molecular mechanisms of
      synaptic plasticity is increasing and will be enhanced further with more complete
      descriptions and sharing of the published models.

PMID- 21188164
TI  - Divalent metal- and high mobility group N protein-dependent nucleosome stability
      and conformation.
AB  - High mobility group N proteins (HMGNs) bind specifically to the nucleosome core
      and act as chromatin unfolding and activating factors. Using an all-Xenopus
      system, we found that HMGN1 and HMGN2 binding to nucleosomes results in distinct
      ion-dependent conformation and stability. HMGN2 association with nucleosome core
      particle or nucleosomal array in the presence of divalent metal triggers a
      reversible transition to a species with much reduced electrophoretic mobility,
      consistent with a less compact state of the nucleosome. Residues outside of the
      nucleosome binding domain are required for the activity, which is also displayed
      by an HMGN1 truncation product lacking part of the regulatory domain. In
      addition, thermal denaturation assays show that the presence of 1 mM Mg(2+)> or
      Ca(2+) gives a reduction in nucleosome core terminus stability, which is further
      substantially diminished by the binding of HMGN2 or truncated HMGN1. Our findings
      emphasize the importance of divalent metals in nucleosome dynamics and suggest
      that the differential biological activities of HMGNs in chromatin activation may
      involve different conformational alterations and modulation of nucleosome core
      stability.

PMID- 21188165
TI  - Targeting the OB-Folds of Replication Protein A with Small Molecules.
AB  - Replication protein A (RPA) is the main eukaryotic single-strand (ss) DNA-binding
      protein involved in DNA replication and repair. We have identified and developed
      two classes of small molecule inhibitors (SMIs) that show in vitro inhibition of
      the RPA-DNA interaction. We present further characterization of these SMIs with
      respect to their target binding, mechanism of action, and specificity. Both
      reversible and irreversible modes of inhibition are observed for the different
      classes of SMIs with one class found to specifically interact with DNA-binding
      domains A and B (DBD-A/B) of RPA. In comparison with other
      oligonucleotide/oligosaccharide binding-fold (OB-fold) containing ssDNA-binding
      proteins, one class of SMIs displayed specificity for the RPA protein. Together
      these data demonstrate that the specific targeting of a protein-DNA interaction
      can be exploited towards interrogating the cellular activity of RPA as well as
      increasing the efficacy of DNA-damaging chemotherapeutics used in cancer
      treatment.

PMID- 21188166
TI  - Ultrastructure of Sheep Primordial Follicles Cultured in the Presence of Indol
      Acetic Acid, EGF, and FSH.
AB  - The aim of this study was to investigate the ultrastructural characteristics of
      primordial follicles after culturing of sheep ovarian cortical slices in the
      presence of indol acetic acid (IAA), Epidermal Growth Factor (EGF), and FSH. To
      evaluate ultrastructure of primordial follicles cultured in MEM (control) or in
      MEM containing IAA, EGF, and FSH, fragments of cultured tissue were processes for
      transmission electron microscopy. Except in the control, primordial follicles
      cultured in supplemented media for 6 d were ultrastructurally normal. They had
      oocyte with intact nucleus and the cytoplasm contained heterogeneous-sized lipid
      droplets and numerous round or elongated mitochondria with intact parallel
      cristae were observed. Rough endoplasmic reticulum (RER) was rarely found. The
      granulosa cells cytoplasm contained a great number of mitochondria and abundant
      RER. In conclusion, the presence of IAA, EGF, and FSH helped to maintain
      ultrastructural integrity of sheep primordial follicles cultured in vitro.

PMID- 21188167
TI  - Management of patients with hernia or incisional hernia undergoing surgery for
      morbid obesity.
AB  - Morbidly obese patients (MOPs) are predisposed to developing abdominal wall
      hernias with the potential complication of small bowel obstruction and other
      morbidity. We report our experience in treating morbidly obese patients. Hernia
      prophylaxis has been attempted as a means of decreasing the incisional hernia
      risk associated with weight loss surgery. The controversy regarding the optimal
      time and method of repair of abdominal wall hernias in patients undergoing open
      or laparoscopic gastric bypass is discussed with emphasis placed on either a
      simultaneous repair or splits of the omentum, and of leaving a plug in the hernia
      defect, to allow time to perform a delayed repair.

PMID- 21188168
TI  - Effect of laparoscopic adjustable gastric banding on metabolic syndrome and its
      risk factors in morbidly obese adolescents.
AB  - We examined the effect of laparoscopic adjustable gastric banding (LAGB) on
      weight loss, inflammatory markers, and components of the Metabolic Syndrome (MeS)
      in morbidly obese adolescents and determined if those with MeS lose less weight
      post-LAGB than those without. Data from 14-18 yr adolescents were obtained at
      baseline, 6 and 12 months following LAGB. Significant weight loss and
      improvements in MeS components were observed 6 months and one year following
      LAGB. The incidence of MeS declined 56.8% after 6 months and 69.6% after 12
      months. There was no significant difference in amount of weight lost post-LAGB
      between those with and without MeS at either timepoint. Correlations between
      change in weight parameters and components of MeS in those with and without MeS
      at baseline were examined and found to vary by diagnostic category. LAGB is
      effective for short-term improvement in weight, inflammatory markers, and
      components of MeS in morbidly obese adolescents.

PMID- 21188170
TI  - Placental leucine aminopeptidase- and aminopeptidase A- deficient mice offer
      insight concerning the mechanisms underlying preterm labor and preeclampsia.
AB  - Preeclampsia and preterm delivery are important potential complications in
      pregnancy and represent the leading causes for maternal and perinatal morbidity
      and mortality. The mechanisms underlying both diseases remain unknown, thus
      available treatments (beta2-stimulants and magnesium sulfate) are essentially
      symptomatic. Both molecules have molecular weights less than 5-8  kDa, cross the
      placental barrier, and thus exert their effects on the fetus. The fetus produces
      peptides that are highly vasoactive and uterotonic and increase in response to
      maternal stress and with continued development. Fetal peptides are also small
      molecules that inevitably leak across into the maternal circulation.
      Aminopeptidases such as placental leucine aminopeptidase (P-LAP) and
      aminopeptidase A (APA) are large molecules that do not cross the placental
      barrier. We have shown that APA acts as an antihypertensive agent in the pregnant
      spontaneously hypertensive rat by degrading vasoactive peptides and as a result
      returns the animal to a normotensive state. P-LAP also acts as an antiuterotonic
      agent by degrading uterotonic peptides and thus prolongs gestation in the
      pregnant mouse. Given the ever increasing worldwide incidences of preeclampsia
      and preterm labor, it is imperative that new agents be developed to safely
      prolong gestation. We believe that the use of aminopeptidases hold promise in
      this regard.

PMID- 21188169
TI  - Cancer stem cells: repair gone awry?
AB  - Because cell turnover occurs in all adult organs, stem/progenitor cells within
      the stem-cell niche of each tissue must be appropriately mobilized and
      differentiated to maintain normal organ structure and function. Tissue injury
      increases the demands on this process, and thus may unmask defective regulation
      of pathways, such as Hedgehog (Hh), that modulate progenitor cell fate. Hh
      pathway dysregulation has been demonstrated in many types of cancer, including
      pancreatic and liver cancers, in which defective Hh signaling has been linked to
      outgrowth of Hh-responsive cancer stem-initiating cells and stromal elements.
      Hence, the Hh pathway might be a therapeutic target in such tumors.

PMID- 21188171
TI  - Histone deacetylase inhibitors in the treatment of hematological malignancies and
      solid tumors.
AB  - The human genome is epigenetically organized through a series of modifications to
      the histone proteins that interact with the DNA. In cancer, many of the proteins
      that regulate these modifications can be altered in both function and expression.
      One example of this is the family of histone deacetylases (HDACs), which as their
      name implies remove acetyl groups from the histone proteins, allowing for more
      condensed nucleosomal structure. HDACs have increased expression in cancer and
      are also believed to promote carcinogenesis through the acetylation and
      interaction with key transcriptional regulators. Given this, small molecule
      histone deacetylases inhibitors have been identified and developed, which not
      only inhibit HDACs, but can also lead to growth arrest, differentiation, and/or
      apoptosis in tumors both in vitro and in vivo. Here, we will discuss some of the
      recent developments in clinical trials utilizing HDACs inhibitors for the
      treatment of both hematological malignancies as well as solid tumors.

PMID- 21188172
TI  - p53: the attractive tumor suppressor in the cancer research field.
AB  - p53 is one of the most studied tumor suppressors in the cancer research field. Of
      note, over 50% of human tumors carry loss of function mutations, and thus p53 has
      been considered to be a classical Knudson-type tumor suppressor. From the
      functional point of view, p53 is a nuclear transcription factor to transactivate
      a variety of its target genes implicated in the induction of cell cycle arrest,
      DNA repair, and apoptotic cell death. In response to cellular stresses such as
      DNA damage, p53 is activated and promotes cell cycle arrest followed by the
      replacement of DNA lesions and/or apoptotic cell death. Therefore, p53 is able to
      maintain the genomic integrity to prevent the accumulation of genetic
      alterations, and thus stands at a crossroad between cell survival and cell death.
      In this paper, we describe a variety of molecular mechanisms behind the
      regulation of p53.

PMID- 21188175
TI  - Hypothesis: soluble abeta oligomers in association with redox-active metal ions
      are the optimal generators of reactive oxygen species in Alzheimer's disease.
AB  - Considerable evidence points to oxidative stress in the brain as an important
      event in the early stages of Alzheimer's disease (AD). The transition metal ions
      of Cu, Fe, and Zn are all enriched in the amyloid cores of senile plaques in AD.
      Those of Cu and Fe are redox active and bind to Abeta in vitro. When bound, they
      can facilitate the reduction of oxygen to hydrogen peroxide, and of the latter to
      the hydroxyl radical. This radical is very aggressive and can cause considerable
      oxidative damage. Recent research favours the involvement of small, soluble
      oligomers as the aggregating species responsible for Abeta neurotoxicity. We
      propose that the generation of reactive oxygen species (i.e., hydrogen peroxide
      and hydroxyl radicals) by these oligomers, in association with redox-active metal
      ions, is a key molecular mechanism underlying the pathogenesis of AD and some
      other neurodegenerative disorders.

PMID- 21188174
TI  - Identification of urinary biomarkers of colon inflammation in IL10-/- mice using
      Short-Column LCMS metabolomics.
AB  - The interleukin-10-deficient (IL10(-/-)) mouse develops colon inflammation in
      response to normal intestinal microflora and has been used as a model of Crohn's
      disease. Short-Column LCMS metabolite profiling of urine from IL10(-/-) and wild
      type (WT) mice was used, in two independent experiments, to identify mass
      spectral ions differing in intensity between these two genotypes. Three
      differential metabolites were identified as xanthurenic acid and as the
      glucuronides of xanthurenic acid and of alpha-CEHC (2,5,7,8-tetramethyl-2-(2'
      carboxyethyl)-6-hydroxychroman). The significance of several differential
      metabolites as potential biomarkers of colon inflammation was evaluated in an
      experiment which compared metabolite concentrations in IL10(-/-) and WT mice
      housed, either under conventional conditions and dosed with intestinal
      microflora, or maintained under specific pathogen-free (SPF) conditions.
      Concentrations of xanthurenic acid, alpha-CEHC glucuronide, and an unidentified
      metabolite m/z 495(-)/497(+) were associated with the degree of inflammation in
      IL10(-/-) mice and may prove useful as biomarkers of colon inflammation.

PMID- 21188173
TI  - Manipulating protein acetylation in breast cancer: a promising approach in
      combination with hormonal therapies?
AB  - Estrogens play an essential role in the normal physiology of the breast as well
      as in mammary tumorigenesis. Their effects are mediated by two nuclear estrogen
      receptors, ERalpha and beta, which regulate transcription of specific genes by
      interacting with multiprotein complexes, including histone deacetylases (HDACs).
      During the past few years, HDACs have raised great interest as therapeutic
      targets in the field of cancer therapy. In breast cancer, several experimental
      arguments suggest that HDACs are involved at multiple levels in mammary
      tumorigenesis: their expression is deregulated in breast tumors; they interfere
      with ER signaling in intricate ways, restoring hormone sensitivity in models of
      estrogen resistance, and they clinically represent new potential targets for
      HDACs inhibitors (HDIs) in combination with hormonal therapies. In this paper, we
      will describe these different aspects and underline the clinical interest of HDIs
      in the context of breast cancer resistance to hormone therapies (HTs).

PMID- 21188192
TI  - Protective Role of rAAV-NDI1, Serotype 5, in an Acute MPTP Mouse Parkinson's
      Model.
AB  - Defects in mitochondrial proton-translocating NADH-quinone oxidoreductase
      (complex I) have been implicated in a number of acquired and hereditary diseases
      including Leigh's syndrome and more recently Parkinson's disease. A limited
      number of strategies have been attempted to repair the damaged complex I with
      little or no success. We have recently shown that the non-proton-pumping,
      internal NADH-ubiquinone oxidoreductase (Ndi1) from Saccharomyces cerevisiae
      (baker's yeast) can be successfully inserted into the mitochondria of mice and
      rats, and the enzyme was found to be fully active. Using recombinant
      adenoassociated virus vectors (serotype 5) carrying our NDI1 gene, we were able
      to express the Ndi1 protein in the substantia nigra (SN) of C57BL/6 mice with an
      expression period of two months. The results show that the AAV serotype 5 was
      highly efficient in expressing Ndi1 in the SN, when compared to a previous model
      using serotype 2, which led to nearly 100% protection when using an acute MPTP
      model. It is conceivable that the AAV-serotype5 carrying the NDI1 gene is a
      powerful tool for proof-of-concept study to demonstrate complex I defects as the
      causable factor in diseases of the brain.

PMID- 21188193
TI  - Vitamin d and multiple sclerosis: correlation, causality, and controversy.
AB  - The last years, many studies reported associations between correlates of vitamin
      D exposure and several correlates of multiple sclerosis (MS) disease activity.
      This review discusses studies on vitamin D status, Expanded Disability Status
      Scale (EDSS) score, and relapse activity of MS. Furthermore, several
      considerations for intervention studies on vitamin D supplementation in MS are
      provided.

PMID- 21188195
TI  - Rituximab administration and reactivation of HBV.
AB  - Rituximab is a drug used for the treatment of B-cell non-Hodgkin's lymphoma, and
      its range of use has expanded to the treatment of collagen diseases such as
      idiopathic thrombocytopenic purpura and rheumatoid arthritis. One serious
      complication of rituximab use is the reactivation of dormant hepatitis B virus,
      and prevention of this phenomenon has become an urgent issue. This paper provides
      a general outline of the problem through an analysis of patient cases that we and
      other groups have experienced to date.

PMID- 21188196
TI  - Hepatitis C and kidney disease.
AB  - Multiple extrahepatic manifestations have been associated with chronic hepatitis
      C, the most important among them being cryoglobulinemia, glomerulonephritis,
      porphyria cutanea tarda, lichen planus, seronegative arthritis, and
      lymphoproliferative disorders as in the sudies of Bonkovsky and Mehta (2001) and
      El-Serag et al. (2002). We will discuss in this paper chronic hepatitis C-
      related kidney disease and course and management of patients with chronic
      hepatitis C in special circumstances like hemodialysis and kidney
      transplantation.

PMID- 21188197
TI  - Retreatment of patients nonresponsive to pegylated interferon and ribavirin with
      daily high-dose consensus interferon.
AB  - Background. Current treatment of chronic hepatitis C with pegylated interferon
      and ribavirin has the ability to eliminate viral infection in about half of the
      patients treated. Therapeutic options, for those with remaining chronic
      hepatitis, will remain limited until novel antivirals become available in the
      future. Consensus interferon is currently available and has demonstrated clinical
      efficacy with superior invitro antiviral activity, but the maximum tolerated dose
      is not defined. Methods. We assessed the efficacy of daily high-dose (24 ug)
      consensus interferon with weight-based (1000-1200 mg daily) ribavirin in HCV
      genotype 1-infected non-responder patients. Results. Six adverse events were
      documented in five patients, and the trial was terminated with no subject
      achieving viral clearance. Conclusions. The occurrence of serious adverse events
      effectively defined the upper limit of acceptable dose, while also revealing that
      this dose did not offer enhanced sustained viral clearance.

PMID- 21188194
TI  - MicroRNAs and Multiple Sclerosis.
AB  - MicroRNAs (miRNAs) have recently emerged as a new class of modulators of gene
      expression. miRNAs control protein synthesis by targeting mRNAs for translational
      repression or degradation at the posttranscriptional level. These noncoding RNAs
      are endogenous, single-stranded molecules approximately 22 nucleotides in length
      and have roles in multiple facets of immunity, from regulation of development of
      key cellular players to activation and function in immune responses. Recent
      studies have shown that dysregulation of miRNAs involved in immune responses
      leads to autoimmunity. Multiple sclerosis (MS) serves as an example of a chronic
      and organ-specific autoimmune disease in which miRNAs modulate immune responses
      in the peripheral immune compartment and the neuroinflammatory process in the
      brain. For MS, miRNAs have the potential to serve as modifying drugs. In this
      review, we summarize current knowledge of miRNA biogenesis and mode of action and
      the diverse roles of miRNAs in modulating the immune and inflammatory responses.
      We also review the role of miRNAs in autoimmunity, focusing on emerging data
      regarding miRNA expression patterns in MS. Finally, we discuss the potential of
      miRNAs as a disease marker and a novel therapeutic target in MS. Better
      understanding of the role of miRNAs in MS will improve our knowledge of the
      pathogenesis of this disease.

PMID- 21188198
TI  - Long-term effects of antiviral therapy in patients with chronic hepatitis C.
AB  - Chronic hepatitis C is a major cause of chronic liver disease globally, and the
      natural history of progression may lead to cirrhosis with liver failure,
      hepatocellular carcinoma, and premature liver-related death. Emerging data
      demonstrates that interferon-based therapy, particularly among those achieving a
      sustained virologic response (SVR), is associated with long-term persistence of
      SVR, improved fibrosis and inflammation scores, reduced incidence of
      hepatocellular carcinoma, and prolonged life expectancy. This reduction in the
      rate of progression has also been demonstrated in patients with chronic hepatitis
      C and cirrhosis in some but not all studies. The majority of these results are
      reported with standard interferon therapy, and long-term results of peginterferon
      plus ribavirin therapy with a higher likelihood of SVR should have a yet greater
      impact on the population of treated patients. The impact on slowing progression
      is greatest in patients with an SVR, less in relapsers, and equivocal in
      nonresponders. Thus, the natural history of chronic hepatitis C after completion
      of antiviral therapy is favorable with achievement of an SVR, although further
      data are needed to determine the likely incremental impact of peginterferon plus
      ribavirin, late long-term effects of therapy, and the benefit of treatment in
      patients with advanced hepatic fibrosis.

PMID- 21188199
TI  - Differential impact of adherence to pegylated interferon and ribavirin in the
      treatment of genotype 1 high viral titer chronic hepatitis C.
AB  - To clarify the impact of adherence, we treated 122 genotype 1 high viral titer
      chronic hepatitis C patients with pegylated interferon (peg-IFN) and ribavirin
      for 48 weeks at nine referral hospitals, and evaluated the prognostic factors
      with a focus on the adherence to the treatment. This study included 68 (55.7%)
      treatment-naive patients and 54 (44.3%) patients who did not respond to the
      previous treatment. Multivariate analysis revealed adherence to peg-IFN and
      ribavirin as the only significant predictor. Sustained virological response (SVR)
      rate was 72.2%, 19.0%, and 27.3% in patients given >=80%, 60%-80%, and <60% dose
      peg-IFN, respectively, and was 68.6%, 41.2%, and 5.3% in those given >=80%, 60%
      80%, and <60% dose ribavirin, respectively. SVR rate sharply fell when exposure
      to peg-IFN was below 80% whereas it decreased in a stepwise manner as for
      ribavirin. Therefore, >=80% of peg-IFN and as much as possible dose of ribavirin
      are desired to achieve SVR in the treatment of genotype 1 high viral titer
      chronic hepatitis C.

PMID- 21188200
TI  - Predictors of virological response to a combination therapy with pegylated
      interferon plus ribavirin including virus and host factors.
AB  - A combination therapy with pegylated interferon (PEG-IFN) plus ribavirin (RBV)
      has made it possible to achieve a sustained virological response (SVR) of 50% in
      refractory cases with genotype 1b and high levels of plasma HCVRNA. Several
      factors including virus mutation and host factors such as age, gender, fibrosis
      of the liver, lipid metabolism, innate immunity, and single nucleotide
      polymorphism (SNPs) are reported to be correlated to therapeutic effects.
      However, it is difficult to determine which factor is the most important
      predictor for an individual patient. Data mining analysis is useful for combining
      all these together to predict the therapeutic effects. It is important to analyze
      blood tests and to predict therapeutic effects prior to initiating treatment.
      Since new anti-HCV agents are under development, it will be necessary in the
      future to select the patients who have a high possibility of achieving SVR if
      treatment is performed with standard regimen.

PMID- 21188202
TI  - Epidemiological and Clinical Features of Hepatitis B Virus Genotypes among
      Immigrants in Southern Italy.
AB  - Background/aims. This study aims to determine the distribution and clinical
      features of HBV-genotypes in a population of immigrants affected by HBV
      infection. Methods. Between 01/2003 and 03/2009, 1623 immigrants were tested for
      HBV-infection. Biochemical and virological activities were determined in HBsAg
      positive patients; HBV-genotypes were determined, by the INNO-LiPA HBV
      Genotyping, in the subjects with HBV DNA detectable. In every patient we
      evaluated the stage and classified the infection as inactive carrier, mild or
      moderate/severe chronic hepatitis, cirrhosis, and/or HCC. Results. Among the
      tested subjects, 191 (11.7%) resulted HBsAg-positive, and in 144/191 (75.4%)
      serum HBV-DNA was detectable. The genotype distribution was as follows: 45,13%
      genotype E, 18,1% genotype D, 15,3% genotype B, 13,2% genotype C, 4,9% genotype
      A, 3,5% mixed genotypes (A-D). The evaluation of liver disease degree showed that
      24.6% patients were inactive carriers of HBV infection, 19.4% presented a
      immunotolerance phase, 34.5% had mild chronic hepatitis, 13.6% had a
      moderate/severe chronic hepatitis, 6.3% had cirrhosis, and 1.6% presented HCC.
      Conclusions. Our study evidences a high prevalence of HBV-infection in
      immigrants, and the potentiality of migratory flow in the introduction of
      genotype non-D hepatitis B virus. The Hepatitis B virus genotypes presented
      significant differences in epidemiological and clinical characteristics.

PMID- 21188201
TI  - Therapeutic vaccination in chronic hepatitis B: preclinical studies in the
      woodchuck.
AB  - Recommended treatment of chronic hepatitis B with interferon-alpha and/or
      nucleos(t)ide analogues does not lead to a satisfactory result. Induction of HBV
      specific T cells by therapeutic vaccination or immunotherapies may be an
      innovative strategy to overcome virus persistence. Vaccination with commercially
      available HBV vaccines in patients did not result in effective control of HBV
      infection, suggesting that new formulations of therapeutic vaccines are needed.
      The woodchuck (Marmota monax) is a useful preclinical model for developing the
      new therapeutic approaches in chronic hepadnaviral infections. Several innovative
      approaches combining antiviral treatments with nucleos(t)ide analogues, DNA
      vaccines, and protein vaccines were tested in the woodchuck model. In this paper
      we summarize the available data concerning therapeutic immunization and gene
      therapy using recombinant viral vectors approaches in woodchucks, which show
      encouraging results. In addition, we present potential innovations in
      immunomodulatory strategies to be evaluated in this animal model.

PMID- 21188203
TI  - Can engineered "designer" T cells outsmart chronic hepatitis B?
AB  - More than 350 million people worldwide are persistently infected with human
      heptatitis B virus (HBV) and at risk to develop liver cirrhosis and
      hepatocellular carcinoma making long-term treatment necessary. While a vaccine is
      available and new antiviral drugs are being developed, elimination of
      persistently infected cells is still a major issue. Recent efforts in adoptive
      cell therapy are experimentally exploring immunotherapeutic elimination of HBV
      infected cells by means of a biological attack with genetically engineered
      "designer" T cells.

PMID- 21188204
TI  - Hepatitis C in haematological patients.
AB  - There is no consensus guideline concerning the management of chronic hepatitis C
      patients during chemotherapy, and immunosuppression. However, there are some
      suggestions in literature that hepatitis C viral load increases during
      chemotherapy and there is a risk of rebound immunity against hepatitis C after
      discontinuation of immunosuppression with a consequent liver injury. A close
      monitoring of liver function of these patients is prudent during treatment of
      haematological malignancy. Antiviral treatment is deferred after the completion
      of chemotherapy and recovery of patients' immunity to minimize the toxicity of
      treatment. A combination of pegylated interferon and ribavirin is the standard
      therapy in hepatitis C infected haematological patients.

PMID- 21188206
TI  - Retroperitoneal inflammatory liposarcoma in a patient with non-hodgkin lymphoma:
      a report highlighting diagnostic pitfalls.
AB  - Well differentiated liposarcoma (WDLS) is the commonest subtype of liposarcoma.
      Recognised subtypes of WDLSs are lipoma-like, sclerosing, spindle cell and
      inflammatory. The inflammatory variant of WDLS also known as "lymphocyte-rich
      liposarcoma" is rare. We present a case of inflammatory WDLS occurring in the
      retroperitoneum, in a patient with a past history of non-Hodgkin lymphoma. We
      outline the histological features, discuss the differential diagnoses and
      highlight the diagnostic pitfalls in interpretation of this lesion on fine needle
      biopsy.

PMID- 21188205
TI  - Hypothyroidism in Noninterferon Treated-HCV Infected Individuals Is Associated
      with Abnormalities in the Regulation of Th17 Cells.
AB  - HCV-Ag-specific TH17 cells secrete IL17, a cytokine involved in autoimmune
      diseases and regulated by IL10 and TGF-b. 5-12% of patients with chronic HCV
      infection have hypothyroidism. We evaluated the role of these cytokines in this
      patients by determining serum concentration of TsH, T3, free T4, IL2, IL10, IL12,
      IL17, TGF-b, anti-TG, TPO, CCP, GBM, and cardiolipin antibodies in 87 chronically
      noninterferon treated HCV-infected patients. 20 patients (group A) had elevated
      TsH values (>5 MUUI/ml) whereas the remaining 67 (group B) had normal values. The
      percentage of anti-TPO, TG, GBM, and cardiolipin antibodies in group A patients
      (33%, 41%, 5% and 5%, resp.) as well as IL17, IL2 and TGF-b concentrations (25 +/
      23 pg/ml, 643 +/- 572 pg/ml, and 618 +/- 221 pg/ml, resp.) were significantly
      higher than group B. Abnormal Th17 regulation mediated by IL-2 and low TGF-b
      concentrations is associated with hypothyroidism in chronically-infected HCV
      patients.

PMID- 21188208
TI  - Distal cervical carotid artery dissection after carotid endarterectomy: a
      complication of indwelling shunt.
AB  - The technical factors and surgical methods employed in carotid endarterectomy are
      controversial. In particular, whether or not to use an indwelling arterial shunt
      during carotid endarterectomy remains a source of conflict. We describe a rare
      case in which uncomplicated carotid endarterectomy was followed by distal
      internal carotid artery dissection and suggest that this devastating complication
      was due to intimal damage produced by the use of an indwelling arterial shunt.

PMID- 21188207
TI  - Leukocyte counts, myeloperoxidase, and pregnancy-associated plasma protein a as
      biomarkers for cardiovascular disease: towards a multi-biomarker approach.
AB  - We evaluated leukocyte counts and levels of CRP, fibrinogen, MPO, and PAPP-A in
      patients with stable and unstable angina pectoris, acute myocardial infarction,
      and healthy controls. All biomarkers were analyzed again after 6 months.
      Leukocyte counts and concentrations of fibrinogen, CRP, MPO, and PAPP-A were
      significantly increased in patients with acute myocardial infarction. Leukocyte
      counts and concentrations of MPO were significantly increased in patients with
      unstable angina pectoris compared with controls. After 6 months, leukocyte counts
      and MPO concentrations were still increased in patients with acute myocardial
      infarction when compared to controls. Discriminant analysis showed that leukocyte
      counts, MPO, and PAPP-A concentrations classified study group designation for
      acute coronary events correctly in 83% of the cases. In conclusion, combined
      assessment of leukocyte counts, MPO, and PAPP-A was able to correctly classify
      acute coronary events, suggesting that this could be a promising panel for a
      multibiomarker approach to assess cardiovascular risk.

PMID- 21188209
TI  - Caffeine's Vascular Mechanisms of Action.
AB  - Caffeine is the most widely consumed stimulating substance in the world. It is
      found in coffee, tea, soft drinks, chocolate, and many medications. Caffeine is a
      xanthine with various effects and mechanisms of action in vascular tissue. In
      endothelial cells, it increases intracellular calcium stimulating the production
      of nitric oxide through the expression of the endothelial nitric oxide synthase
      enzyme. Nitric oxide is diffused to the vascular smooth muscle cell to produce
      vasodilation. In vascular smooth muscle cells its effect is predominantly a
      competitive inhibition of phosphodiesterase, producing an accumulation of cAMP
      and vasodilation. In addition, it blocks the adenosine receptors present in the
      vascular tissue to produce vasoconstriction. In this paper the main mechanisms of
      action of caffeine on the vascular tissue are described, in which it is shown
      that caffeine has some cardiovascular properties and effects which could be
      considered beneficial.

PMID- 21188210
TI  - Infliximab for idiopathic deep cutaneous vasculitis refractory to
      cyclophosphamide.
AB  - Cutaneous vasculitis can be classified as primary or idiopathic; or secondary,
      when it presents as a manifestation of connective tissue diseases, infections,
      drug reactions or malignancies. Although most of the idiopathic cases are self
      limited and responsive to supportive measures and nonsteroidal anti-inflammatory
      drugs, potent immunosuppressants are sometimes required for the management of the
      refractory situations. Here we describe a case of a 32-year-old Caucasian female
      patient with history of idiopathic cutaneous deep vasculitis unresponsive to
      methotrexate, dapsone, and cyclophosphamide who was effectively treated with
      infliximab.

PMID- 21188211
TI  - Worsening renal function in patients hospitalized with acute heart failure: risk
      factors and prognostic significances.
AB  - Objectives. To determine the prevalence, the clinical predictors, and the
      prognostic significances of Worsening Renal Function (WRF) in hospitalized
      patients with Acute Heart Failure (AHF). Methods. 394 consecutively hospitalized
      patients with AHF were evaluated. WRF was defined as an increase in serum
      creatinine of >=0.3 mg/dL from baseline to discharge. Results. Nearly 11% of
      patients developed WRF. The independent predictors of WRF analyzed with a
      multivariable logistic regression were history of chronic kidney disease (P =
      .047), age >75 years (P = .049), and admission heart rates >=100 bpm (P = .004).
      Mortality or rehospitalization rates at 1 month, 6 months, and 1year were not
      significantly different between patients with WRF and those without WRF.
      Conclusion. Different clinical predictors at hospital admission can be used to
      identify patients at increased risk for developing WRF. Patients with WRF
      compared with those without WRF experienced no significant differences in
      hospital length of stay, mortality, or rehospitalization rates.

PMID- 21188212
TI  - Integrative bioinformatics analysis of proteins associated with the cardiorenal
      syndrome.
AB  - The cardiorenal syndrome refers to the coexistence of kidney and cardiovascular
      disease, where cardiovascular events are the most common cause of death in
      patients with chronic kidney disease. Both, cardiovascular as well as kidney
      diseases have been extensively analyzed on a molecular level, resulting in
      molecular features and associated processes indicating a cross-talk of the two
      disease etiologies on a pathophysiological level. In order to gain a
      comprehensive picture of molecular factors contributing to the bidirectional
      interplay between kidney and cardiovascular system, we mined the scientific
      literature for molecular features reported as associated with the cardiorenal
      syndrome, resulting in 280 unique genes/proteins. These features were then
      analyzed on the level of molecular processes and pathways utilizing various types
      of protein interaction networks. Next to well established molecular features
      associated with the renin-angiotensin system numerous proteins involved in signal
      transduction and cell communication were found, involving specific molecular
      functions covering receptor binding with natriuretic peptide receptor and ligands
      as well known example. An integrated analysis of identified features pinpointed a
      protein interaction network involving mediators of hemodynamic change and an
      accumulation of features associated with the endothelin and VEGF signaling
      pathway. Some of these features may function as novel therapeutic targets.

PMID- 21188213
TI  - Her-2/neu testing and therapy in gastroesophageal adenocarcinoma.
AB  - Despite ongoing advances in the treatment of gastroesophageal cancer, prognosis
      remains poor. The best promise to improve this poor survival is provided by new
      targeted agents. Of these, human epidermal growth factor receptor 2 (HER2) is
      currently in the spotlight. In this review, we provide an overview of recent
      developments in HER2 testing and results of clinical trials targeting HER2 in
      gastroesophageal adenocarcinoma. Based on the encouraging ToGA trial findings it
      is now expected that routine HER2 testing will be included in the diagnostic work
      up of patients with advanced gastric cancer. With regard to this testing,
      overexpression of the HER2 protein seems to possess the best predictive
      properties. However, HER2 immunohistochemistry (IHC) is subject to assay and
      interobserver variability, so standardization and internal and external
      proficiency testing is an absolute prerequisite, especially as the IHC scoring
      system in gastric cancer is different from that of breast cancer. Further study
      is needed to investigate the clinical meaning of the significant heterogeneity
      observed in both gene amplification and protein overexpression in
      gastroesophageal cancer. Highly effective therapies for gastroesophageal cancer
      can only be accomplished by a multi-targeted approach, considering crosstalk
      between pathways and continuing to optimize chemotherapy.

PMID- 21188215
TI  - How bacteria-induced apoptosis of intestinal epithelial cells contributes to
      mucosal inflammation.
AB  - The life cycle of an intestinal epithelial cell is terminated by apoptosis and/or
      cell shedding. Apoptotic deletion of epithelial cells from the intact intestinal
      mucosa is not accompanied by detectable inflammatory response or loss of barrier
      function. But increased permeability of the epithelial barrier and increased
      apoptotic rates of epithelial cells have been reported for patients suffering
      from inflammatory bowel disease. Microbiota can both induce or inhibit apoptosis
      of intestinal epithelial cells thus contribute to mucosal inflammation or support
      epithelial integrity respectively. Bacteria-mediated cytokine secretion and
      altered cell signalling are central to epithelial injury. Tumor necrosis factor
      (TNF) secreted after exposure to invasive bacteria induces both apoptosis and
      cell shedding. TNF is the major target gene of the transcription factor nuclear
      factor-kappa B with both pro- and anti-apoptotic effects. Autophagy promotes both
      cell survival and "autophagic" cell death. If autophagy is directed against
      microbes it is termed xenophagy. Inhibition of xenophagy has been shown to
      decrease cell survival. Endoplasmic reticulum (ER) stress causes misfolded
      proteins to accumulate in the ER lumen. It was suggested that ER stress and
      autophagy may interact within intestinal epithelial cells. Apoptosis in response
      to infection may be well proposed by the host to delete infected epithelial cells
      or could be a strategy of microbial pathogens to escape from exhausted cells to
      invade deeper mucosal layers for a prolonged bacterial colonization.

PMID- 21188216
TI  - Neurokinin-1 receptor antagonist treatment in polymicrobial sepsis: molecular
      insights.
AB  - Neurokinin-1 receptor blocking has been shown to be beneficial against lung
      injury in polymicrobial sepsis. In this paper, we evaluated the possible
      mediators and the mechanism involved. Mice were subjected to cecal ligation and
      puncture (CLP-) induced sepsis or sham surgery. Vehicle or SR140333 [1 mg/kg;
      subcutaneous (s.c.)] was administered to septic mice either 30 min before or 1 h
      after the surgery. Lung tissue was collected 8 h after surgery and further
      analyzed. CLP alone caused a significant increase in the activation of the
      transcription factors, protein kinase C-alpha, extracellular signal regulated
      kinases, neurokinin receptors, and substance P levels in lung when compared to
      sham-operated mice. SR140333 injected pre- and post surgery significantly
      attenuated the activation of transcription factors and protein kinase C-alpha and
      the plasma levels of substance P compared to CLP-operated mice injected with the
      vehicle. In addition, GR159897 (0.12 mg/kg; s.c.), a neurokinin-2 receptor
      antagonist, failed to show beneficial effects. We conclude that substance P
      acting via neurokinin-1 receptor in sepsis initiated signaling cascade mediated
      mainly by protein kinase C-alpha, led to NF-kappaB and activator protein-1
      activation, and further modulated proinflammatory mediators.

PMID- 21188214
TI  - Testing for HER2 in Breast Cancer: A Continuing Evolution.
AB  - Human epidermal growth factor receptor 2 (HER2) is an important prognostic and
      predictive factor in breast cancer. HER2 is overexpressed in approximately 15%
      20% of invasive breast carcinomas and is associated with earlier recurrence,
      shortened disease free survival, and poor prognosis. Trastuzumab (Herceptin) a
      "humanized" monoclonal antibody targets the extracellular domain of HER2 and is
      widely used in the management of HER2 positive breast cancers. Accurate
      assessment of HER2 is thus critical in the management of breast cancer. The aim
      of this paper is to present a comprehensive review of HER2 with reference to its
      discovery and biology, clinical significance, prognostic value, targeted therapy,
      current and new testing modalities, and the interpretation guidelines and
      pitfalls.

PMID- 21188217
TI  - Inflammatory bowel diseases: when natural friends turn into enemies-the
      importance of CpG motifs of bacterial DNA in intestinal homeostasis and chronic
      intestinal inflammation.
AB  - From numerous studies during the last years it became evident that bacteria and
      bacterial constituents play a decisive role both in the maintenance of intestinal
      immune homeostasis as well as in the development and perpetuation of chronic
      intestinal inflammation. In this review we focus on the role of bacterial DNA
      which is a potent immunomodulatory component of the bacterial flora. Bacterial
      DNA has been shown to be protective against experimental colitis. In contrast
      bacterial DNA essentially contributes to the perpetuation of an already
      established chronic intestinal inflammation in a Toll-like receptor (TLR)9
      dependent manner. This dichotomic action may be explained by a different
      activation status of essential regulators of TLR signaling like Glycogen synthase
      kinase 3-beta (GSK3-beta) depending on the pre-activation status of the
      intestinal immune system. In this review we suggest that regulators of TLR
      signaling may be interesting therapeutic targets in IBD aiming at the restoration
      of intestinal immune homeostasis.

PMID- 21188218
TI  - Microbial sensing by the intestinal epithelium in the pathogenesis of
      inflammatory bowel disease.
AB  - Recent years have raised evidence that the intestinal microbiota plays a crucial
      role in the pathogenesis of chronic inflammatory bowels diseases. This evidence
      comes from several observations. First, animals raised under germ-free conditions
      do not develop intestinal inflammation in several different model systems.
      Second, antibiotics are able to modulate the course of experimental colitis.
      Third, genetic polymorphisms in a variety of genes of the innate immune system
      have been associated with chronic intestinal inflammatory diseases. Dysfunction
      of these molecules results in an inappropriate response to bacterial and
      antigenic stimulation of the innate immune system in the gastrointestinal tract.
      Variants of pattern recognition receptors such as NOD2 or TLRs by which commensal
      and pathogenic bacteria can be detected have been shown to be involved in the
      pathogenesis of IBD. But not only pathways of microbial detection but also
      intracellular ways of bacterial processing such as autophagosome function are
      associated with the risk to develop Crohn's disease. Thus, the "environment
      concept" and the "genetic concept" of inflammatory bowel disease pathophysiology
      are converging via the intestinal microbiota and the recognition mechanisms for
      an invasion of members of the microbiota into the mucosa.

PMID- 21188219
TI  - The Opportunistic Pathogen Listeria monocytogenes: Pathogenicity and Interaction
      with the Mucosal Immune System.
AB  - Listeria monocytogenes is an opportunistic foodborne pathogen causing
      listeriosis, an often fatal infection leading to meningitis, sepsis, or infection
      of the fetus and abortion in susceptible individuals. It was recently found that
      the bacterium can also cause acute, self-limiting febrile gastroenteritis in
      healthy individuals. In the intestinal tract, L. monocytogenes penetrates the
      mucosa directly via enterocytes, or indirectly via invasion of Peyer's patches.
      Animal models for L. monocytogenes infection have provided many insights into the
      mechanisms of pathogenesis, and the development of new model systems has allowed
      the investigation of factors that influence adaptation to the gastrointestinal
      environment as well as adhesion to and invasion of the intestinal mucosa. The
      mucosal surfaces of the gastrointestinal tract are permanently exposed to an
      enormous antigenic load derived from the gastrointestinal microbiota present in
      the human bowel. The integrity of the important epithelial barrier is maintained
      by the mucosal immune system and its interaction with the commensal flora via
      pattern recognition receptors (PRRs). Here, we discuss recent advances in our
      understanding of the interaction of L. monocytogenes with the host immune system
      that triggers the antibacterial immune responses on the mucosal surfaces of the
      human gastrointestinal tract.

PMID- 21188220
TI  - The role of bacteria and pattern recognition receptors in GVHD.
AB  - Graft-versus-Host Disease (GvHD) is the most serious complication of allogeneic
      stem cell transplantation (SCT) and results from an activation of donor
      lymphocytes by recipient antigen-presenting cells (APCs). For a long time, it has
      been postulated that the intestinal microflora and endotoxin exert a crucial step
      in this APC activation, as there is early and severe gastrointestinal damage
      induced by pretransplant conditioning. With the detailed description of pathogen
      associated molecular patterns and pathogen recognition receptors single
      nucleotide polymorphisms of TLRs and especially NOD2 have been identified as
      potential risk factors of GvHD and transplant related complications thus further
      supporting the crucial role of innate immunity in SCT, related complications.
      Gastrointestinal decontamination and neutralization of endotoxin have been used
      to interfere with this early axis of activation with some success but more
      specific approaches of modulation of innate immunity are needed for further
      improvement of clinical outcome.

PMID- 21188222
TI  - Suppression of tumorigenesis: modulation of inflammatory cytokines by oral
      administration of microencapsulated probiotic yogurt formulation.
AB  - The objective of this study was to examine the ability of a novel
      microencapsulated probiotic yogurt formulation to suppress the intestinal
      inflammation. We assessed its anticancer activity by screening interleukin-1, 6,
      and 12 (IL-1, 6, 12), secretory levels of tumor necrosis factor-alpha (TNF
      alpha), interferon-gamma (IFN-gamma), prostaglandin E(2)  (PGE(2)), and
      thromboxane B2 in the digesta obtained from the duodenum, jejunum, proximal, and
      distal segments of the ileum of C57BL/6J-Apc(Min)/J mice. Formulation-receiving
      animals showed consistently lower proinflammatory cytokines' levels when compared
      to control group animals receiving empty alginate-poly-L-lysine-alginate (APA)
      microcapsules suspended in saline. The concentrations of IL-12 found in serum in
      control and treatment group animals were significant: 46.58 +/- 16.96 pg/mL and
      158.58 +/- 28.56 pg/mL for control and treatment animals, respectively. We
      determined a significant change in plasma C-reactive protein: 81.04 +/- 23.73
      ng/mL in control group and 64.21 +/- 16.64 ng/mL in treatment group. Western
      blots showed a 71% downregulation of cyclooxygenase-2 (COX-2) protein in
      treatment group animals compared to control. These results point to the
      possibility of using this yogurt formulation in anticancer therapies, in addition
      to chronic gut diseases such as Crohn's disease, irritable bowel syndrome (IBS),
      and inflammatory bowel disease (IBD) thanks to its inflammation lowering
      properties.

PMID- 21188223
TI  - The bowel microbiota and inflammatory bowel diseases.
AB  - The human bowel contains a large and biodiverse bacterial community known as the
      microbiota or microbiome. It seems likely that the microbiota, fractions of the
      microbiota, or specific species comprising the microbiota provide the antigenic
      fuel that drives the chronic immune inflammation of the bowel mucosa that is
      characteristic of Crohn's disease and ulcerative colitis. At least twenty years
      of microbiological research have been expended on analysis of the composition of
      the bowel microbiota of inflammatory bowel disease patients in comparison to that
      of control subjects. Despite extensive speculations about the aetiological role
      of dysbiosis in inflammatory bowel diseases, knowledge that can be easily
      translated into effective remedies for patients has not eventuated. The causes of
      this failure may be due to poorly defined and executed bacteriological studies,
      as well as the overwhelming complexity of a biome that contains hundreds of
      bacterial species and trillions of bacterial cells.

PMID- 21188224
TI  - Lyme Neuroborreliosis: Preliminary Results from an Urban Referral Center
      Employing Strict CDC Criteria for Case Selection.
AB  - Lyme neuroborreliosis or "neurological Lyme disease" was evidenced in 2 of 23
      patients submitted to strict criteria for case selection of the Centers for
      Disease Control and Prevention employing a two-tier test to detect antibodies to
      Borrelia burgdorferi at a single institution. One patient had symptomatic
      polyradiculoneuritis, dysautonomia, and serological evidence of early infection;
      and another had symptomatic small fiber sensory neuropathy, distal
      polyneuropathy, dysautonomia, and serological evidence of late infection. In the
      remaining patients symptoms initially ascribed to Lyme disease were probably
      unrelated to B. burgdorferi infection. Our findings suggest early susceptibility
      and protracted involvement of the nervous system most likely due to the
      immunological effects of B. burgdorferi infection, although the exact mechanisms
      remain uncertain.

PMID- 21188221
TI  - Peyer's Patches: The Immune Sensors of the Intestine.
AB  - The gut-associated lymphoid tissue (GALT) consists of isolated or aggregated
      lymphoid follicles forming Peyer's patches (PPs). By their ability to transport
      luminal antigens and bacteria, PPs can be considered as the immune sensors of the
      intestine. PPs functions like induction of immune tolerance or defense against
      pathogens result from the complex interplay between immune cells located in the
      lymphoid follicles and the follicle-associated epithelium. This crosstalk seems
      to be regulated by pathogen recognition receptors, especially Nod2. Although TLR
      exerts a limited role in PP homeotasis, Nod2 regulates the number, size, and T
      cell composition of PPs, in response to the gut flora. In turn, CD4(+) T-cells
      present in the PP are able to modulate the paracellular and transcellular
      permeabilities. Two human disorders, Crohn's disease and graft-versus-host
      disease are thought to be driven by an abnormal response toward the commensal
      flora. They have been associated with NOD2 mutations and PP dysfunction.

PMID- 21188225
TI  - Medial orbitofrontal cortex is associated with fatigue sensation.
AB  - Fatigue is an indispensable bioalarm to avoid exhaustive state caused by overwork
      or stresses. It is necessary to elucidate the neural mechanism of fatigue
      sensation for managing fatigue properly. We performed H(2) ( 15)O positron
      emission tomography scans to indicate neural activations while subjects were
      performing 35-min fatigue-inducing task trials twice. During the positron
      emission tomography experiment, subjects performed advanced trail-making tests,
      touching the target circles in sequence located on the display of a touch-panel
      screen. In order to identify the brain regions associated with fatigue sensation,
      correlation analysis was performed using statistical parametric mapping method.
      The brain region exhibiting a positive correlation in activity with subjective
      sensation of fatigue, measured immediately after each positron emission
      tomography scan, was located in medial orbitofrontal cortex (Brodmann's area
      10/11). Hence, the medial orbitofrontal cortex is a brain region associated with
      mental fatigue sensation. Our findings provide a new perspective on the neural
      basis of fatigue.

PMID- 21188226
TI  - Analysis on the susceptibility genes in two chinese pedigrees with familial
      Parkinson's disease.
AB  - Objective. To screen the susceptibility genes in Chinese pedigrees with early
      onset familial Parkinson's disease (FPD). Methods. Fifty-one genomic DNA samples
      extracted from two Chinese pedigrees with FPD, the alpha-synuclein genes (SNCA),
      the leucine-rich repeat kinase 2(LRRK2), PINK1(PTEN-induced putative kinase 1),
      PARK7(Protein DJ1), PARK2(Parkinson juvenile disease protein 2), the
      glucocerebrosidase (GBA), and ATP(Ezrin-binding protein PACE-1), were sequenced
      by the use of polymerase chain reaction (PCR) technique. The gene dose of SNCA
      was checked. Results. There were only two missense mutations observed,
      respectively, at exon 5 of LRRK2 and exon 10 of PARK2, and both were enrolled in
      SNPs. Conclusion. No meaningful mutations could be detected, and other
      susceptibility genes should be detected in FDP patients in China.

PMID- 21188227
TI  - Early bifrontal brain injury: disturbances in cognitive function development.
AB  - We describe six psychomotor, language, and neuropsychological sequential
      developmental evaluations in a boy who sustained a severe bifrontal traumatic
      brain injury (TBI) at 19 months of age. Visuospatial, drawing, and writing skills
      failed to develop normally. Gradually increasing difficulties were noted in
      language leading to reading and spontaneous speech difficulties. The last two
      evaluations showed executive deficits in inhibition, flexibility, and working
      memory. Those executive abnormalities seemed to be involved in the other
      impairments. In conclusion, early frontal brain injury disorganizes the
      development of cognitive functions, and interactions exist between executive
      function and other cognitive functions during development.

PMID- 21188228
TI  - IgD Multiple Myeloma Paraproteinemia as a Cause of Myositis.
AB  - A 48-years old man was diagnosed an IgD-k multiple myeloma (MM) at age 38 years
      for which he successfully underwent chemotherapy and bone marrow transplant. He
      then developed a graft-versus-host disease (GVHD) whose manifestations included,
      three years later, a polymyositis, diagnosed at muscle biopsy and successfully
      treated with steroids. Few months after polymyositis remission, myeloma relapsed
      and the patient was treated with thalidomide for six years with good remission.
      Soon after thalidomide suspension, MM relapsed again and the patient came to our
      observation for a new onset of neuromuscular symptoms. He underwent both muscle
      and peripheral nerve biopsy to discriminate between myositis (paraproteinemia
      versus GVHD), amyloidosis, and thalidomide toxicity. The first muscle biopsy
      showed an inflammatory pattern with necrotic fibres, macrophagical invasion (CD68
      positive), rare interstitial cellular infiltrates (CD8 positive and CD4
      negative), widespread anti-HLA positivity and negative antiMAC. The second muscle
      biopsy showed the same inflammatory pattern plus an involvement of blood vessels.
      Direct immunofluorescence for IgD showed diffuse positivity along the sarcolemmal
      in both muscle biopsies. Sural nerve biopsy demonstrated both demyelinating and
      axonal aspects with no inflammatory infiltrates, but positivity for HLA and MAC.
      Congo Red was negative in both skeletal muscle and peripheral nerve.

PMID- 21188229
TI  - Population ageing in ghana: research gaps and the way forward.
AB  - This paper attempts to highlight research gaps and what should be done concerning
      population ageing in the Ghanaian context. The proportion of the elderly
      increased from 4.9 percent in 1960 to 7.2 percent in 2000, while the number rose
      from 0.3 million to 1.4 million over the same period (an increase of 367
      percent). Projection results indicate that by 2050, the aged population will
      account for 14.1 percent of the total population. Very little is known about the
      living arrangements and health profile of Ghana's older population. With
      increasing urbanization and modernization, it is important to know something
      about intergenerational transfers from adult children to their elderly parents,
      and characterize the elderly persons' food security strategies. Training of
      researchers will be important in terms of strengthening Ghana's capacity to
      monitor trends, as well as to conduct research and explore new directions in
      population ageing research.

PMID- 21188230
TI  - Moderate resistive training maintains bone mineral density and improves
      functional fitness in postmenopausal women.
AB  - Twenty five subjects were randomized to untrained (UN) and resistive-trained (RT)
      groups. The RT group exercised three sessions per week at 60%-70% of the load
      according to individual 1RM test during 24 weeks. Both groups were evaluated
      before and after protocol period assessing lumbar spine (LS) and femoral neck
      (FN) BMD by dual-energy X-ray absorptiometry, VO(2) max, and neuromuscular
      fitness. After 24 weeks, there were significant reductions in LS (0.89 +/- 0.16%
      loss) and FN BMD (1.54 +/- 0.35% loss) for UN but no change was found in the TR
      (LS: 0.01 +/- 0.12% and FN: 0.04 +/- 0.05% loss). The UN group had no changes in
      neuromuscular performance. However, RT exhibited a significant improvement on the
      functional fitness parameters evaluated, with the exception of agility. Our
      results indicate RT suppresses the decline in BMD and simultaneously improves the
      functional fitness of postmenopausal women without hormone replacement therapy,
      which may reduce fall risk and related bone fractures.

PMID- 21188231
TI  - Repeatability of a short food frequency questionnaire to assess calcium intake in
      older australians.
AB  - Objective. To assess the repeatability of the validated Flinders Calcium Food
      Frequency Questionnaire (FFQ(CA)) for estimating dietary calcium intake in a
      sample of community dwelling older Australians. Methods. A test-retest
      repeatability study involving 100 subjects (>=65 years) living independently in
      metropolitan Adelaide, Australia. Estimates of daily calcium intake from the
      first (FFQ(CA1)) and repeated administration (FFQ(CA2)) were calculated from two
      versions (35-item and 15-item) of the FFQ(CA). The intraclass correlation
      coefficient (ICC) was used to assess the repeatability. Results. Moderate and
      comparable ICC values (r = 0.5, r = 0.6) were found across the two versions of
      the FFQ(CA). Conclusion. Both FFQ(CA) versions demonstrated moderate
      repeatability, supporting the results of previous studies.

PMID- 21188232
TI  - Basal cell carcinoma in a child.
AB  - Basal cell carcinoma is the most commonly seen nonmelanoma skin cancer which is
      rarely encountered in the childhood period. An 11-year old child was admitted to
      our clinic due to an erythematous and a slightly pigmented lesion with a 3 * 4 cm
      diameter on his posterior scalp. Macroscopically, the lesion was excised with a
      10 mm safety margin. Pathologic examination revealed a basal cell carcinoma. No
      symptoms or signs of a syndrome were observed both in the patient and his family.

PMID- 21188233
TI  - No-needle jet intradermal aminolevulinic Acid photodynamic therapy for recurrent
      nodular Basal cell carcinoma of the nose: a case report.
AB  - Photodynamic therapy (PDT) with aminolevulinic acid (ALA) to treat nodular basal
      cell carcinoma (BCC) has been shown to be beneficial. The success rate of ALA-PDT
      in the treatment of nodular BCC is dependent on optimal penetration of the
      photosensitizing agent and subsequent PpIX production. To enhance topical
      delivery of drugs intradermally, a needleless jet injection (NLJI), which employs
      a high-speed jet to puncture the skin without the side effects of needles, was
      used in one patient with recurrent BCC of the nose. Photoactivation was then
      performed using red light emitting diode [CW @ lambda 630 nm, irradiance 50
      mW/cm(2), total fluence 51 J/cm(2)] for 17 minutes. Excellent cosmesis was
      obtained. Aside from mild crusting present for six days, no other adverse signs
      were noted. Clinically, there was no recurrent lesion up two years
      postintervention. Additional studies in larger samples of subjects are needed to
      further evaluate this promising technique.

PMID- 21188234
TI  - Assessment of transformed properties in vitro and of tumorigenicity in vivo in
      primary keratinocytes cultured for epidermal sheet transplantation.
AB  - Epidermal keratinocytes are used as a cell source for autologous and allogenic
      cell transplant therapy for skin burns. The question addressed here is to
      determine whether the culture process may induce cellular, molecular, or genetic
      alterations that might increase the risk of cellular transformation.
      Keratinocytes from four different human donors were investigated for molecular
      and cellular parameters indicative of transformation status, including (i)
      karyotype, (ii) telomere length, (iii) proliferation rate, (iv) epithelial
      mesenchymal transition, (v) anchorage-independent growth potential, and (vi)
      tumorigenicity in nude mice. Results show that, despite increased cell survival
      in one keratinocyte strain, none of the cultures displayed characteristics of
      cell transformations, implying that the culture protocol does not generate
      artefacts leading to the selection of transformed cells. We conclude that the
      current protocol does not result in an increased risk of tumorigenicity of
      transplanted cells.

PMID- 21188235
TI  - Two distinct pathways to development of squamous cell carcinoma of the vulva.
AB  - Squamous cell carcinoma (SCC) accounts for approximately 95% of the malignant
      tumors of the vaginal vulva and is mostly found in elderly women. The future
      numbers of patients with vulvar SCC is expected to rise, mainly because of the
      proportional increase in the average age of the general population. Two different
      pathways for vulvar SCC have been put forth. The first pathway is triggered by
      infection with a high-risk-type Human Papillomavirus (HPV). Integration of the
      HPV DNA into the host genome leads to the development of a typical vulvar
      intraepithelial neoplasia (VIN), accompanied with overexpression of p14(ARF) and
      p16(INK4A). This lesion subsequently forms a warty- or basaloid-type SCC. The HPV
      vaccine is a promising new tool for prevention of this HPV related SCC of the
      vulva. The second pathway is HPV-independent. Keratinizing SCC develops within a
      background of lichen sclerosus (LS) through a differentiated VIN. It has a
      different set of genetic alterations than those in the first pathway, including
      p53 mutations, allelic imbalances (AI), and microsatellite instability (MSI).
      Further clinical and basic research is still required to understand and prevent
      vulvar SCC. Capsule. Two pathway for pathogenesis of squamous cell carcinoma of
      the value are reviewed.

PMID- 21188236
TI  - Fc gamma RIIA Genotypes and Its Association with Anti-C1q Autoantibodies in Lupus
      Nephritis (LN) Patients from Western India.
AB  - To identify Fc gamma RIIA genotypes in Systemic Lupus Erythematosus (SLE)
      patients and their association with anti-C1q antibodies. Methods. Fc gamma RIIA
      genotyping was done in eighty Indian SLE patients and eighty healthy controls
      using allele-specific PCR. Anti-C1q antibodies were measured by ELISA. Results.
      LN patients showed higher SLEDAI (6-32) as compared to SLE patients without renal
      manifestations and had SLEDAI between 6-23. Fc gamma RIIA polymorphic frequency
      in SLE patients was R131/H131 (67.5%), R131/R131 (20%) and H131/ H131 (12.5%) as
      against that of normal population (62.5%, 10%, and 27.5%), respectively. Sixty
      two patients (77.5%) showed positivity for anti-C1q antibodies. LN patients
      showed elevated levels of anti-C1q antibodies (258.2 u/ml +/- 38.5 U/mL) as
      compared to SLE patients without nephritis (134.6 +/- 24.6 U/mL). Among anti-C1q
      positive patients, 71% had R131/H131 genotype, 22.6% had R131/R131 and remaining
      6.4%, patients had H131/H131 genotype. All anti-C1q positive patients with
      R131/R131 genotype had elevated levels of anti-C1q antibodies (>100 U/ml),
      whereas among anti-C1q negative patients, none had R131/R131 genotype.
      Conclusion. This first report on Indian SLE patients supports the hypothesis that
      Fc gamma RIIA R131 variant over expression may constitute a susceptibility factor
      for development of severe SLE manifestations in LN patients.

PMID- 21188237
TI  - Addison's Disease Revisited in Poland: Year 2008 versus Year 1990.
AB  - This study aimed at comparing two groups of patients with Addison's disease: A,
      including 180 patients described in 1991 and B, consisting of 138 patients
      registered since 1991. The incidence of coexisting autoimmune disorders was
      evaluated and etiological factors were analyzed. Immunological and imaging
      studies (computed tomography in group B) were performed. Adrenal autoantibodies
      were examined by an indirect immunofluorescence technique in group A, and by the
      assay measuring autoantibodies against steroid 21-hydroxylase in group B. Adrenal
      autoantibodies were revealed in 37% of patients examined by the
      immunofluorescence method and in 63% investigated by the modern technique.
      Tuberculosis was found in 52 patients in the group A and in two patients in the
      group B; metastatic infiltrations of the adrenals in CT were detected in 16
      patients. Probable autoimmune Addison's disease was diagnosed in 125/180 patients
      (69%) in the group A and in 116/138 patients (84%) in the group B.

PMID- 21188238
TI  - 5-androstenediol ameliorates pleurisy, septic shock, and experimental autoimmune
      encephalomyelitis in mice.
AB  - Androstenediol (androst-5-ene-3beta,17beta-diol; 5-AED), a natural adrenal
      steroid, has been shown to suppress experimental autoimmune encephalomyelitis
      (EAE) in female SJL/J mice. We here report that 5-AED limits inflammation and
      proinflammatory cytokines including TNFalpha in murine models of carrageenan
      induced pleurisy and lippopolysaccaride- (LPS) induced septic shock. 5-AED binds
      to and transactivates sex steroid receptors with the same general rank order of
      potency (ERbeta > ERalpha ? AR). 5-AED provides benefit in EAE in a dose
      dependent fashion, even when treatment is delayed until onset of disease. The
      minimally effective dose may be as low as 4 mg/kg in mice. However, benefit was
      not observed when 5-AED was given in soluble formulation, leading to a short half
      life and rapid clearance. These observations suggest that treatment with 5-AED
      limits the production of pro-inflammatory cytokines in these animal models and,
      ultimately, when formulated and administered properly, may be beneficial for
      patients with multiple sclerosis and other Th1-driven autoimmune diseases.

PMID- 21188239
TI  - Antigen-Experienced CD4lo T Cells Are Linked to Deficient Contraction of the
      Immune Response in Autoimmune Diabetes.
AB  - Following proper activation, naive "CD4lo" T cells differentiate into effector T
      cells with enhanced expression of CD4 -"CD4hi" effectors. Autoimmune diabetes
      prone NOD mice display a unique set of antigen-experienced "CD4lo" T cells that
      persist after primary stimulation. Here, we report that a population of such
      cells remained after secondary and tertiary TCR stimulation and produced
      cytokines upon antigenic challenge. However, when NOD blasts were induced in the
      presence of rIL-15, the number of antigen-experienced "CD4lo" T cells was
      significantly reduced. Clonal contraction, mediated in part by CD95-dependent
      activation-induced cell death (AICD), normally regulates the accumulation of
      "CD4hi" effectors. Interestingly, CD95 expression was dramatically reduced on the
      AICD-resistant NOD "CD4lo" T cells. Thus, while autoimmune disease has often been
      attributed to the engagement of robust autoimmunity, we suggest that the
      inability to effectively contract the immune response distinguishes benign
      autoimmunity from progressive autoimmune diseases that are characterized by
      chronic T cell-mediated inflammation.

PMID- 21188240
TI  - Recovery of renal function after one-year of dialysis treatment: case report and
      registry data.
AB  - Objective. Uncertainty has arisen as to whether renal function can be recovered
      from after long-term regular dialysis treatment. We therefore conducted an
      analysis and scrutinized one patient report. Material and Methods. Swedish
      registry of patients with kidney disease and one patient case. Results. 39
      patients (0.2%) from the Swedish registry comprising 17590 patients who commenced
      RRT (renal replacement therapy) between 1991 and 2008 had recovered from renal
      function after more than 365 days of regular dialysis treatment. The most common
      diagnosis was renovascular disease with hypertension but a large group had uremia
      of unknown cause. HUS, cortical/tubular necrosis, and autoimmune diseases were
      also found. The mean treatment time before withdrawal was 2 years. Conclusions. A
      small number of patients recover after a long period of regular dialysis
      treatment. One could discuss whether it is difficult to identify patients who
      have recovered while undergoing regular dialysis treatment. Regular monitoring of
      renal function may be important.

PMID- 21188241
TI  - Waist-to-Hip Ratio, Cardiovascular Outcomes, and Death in Peritoneal Dialysis
      Patients.
AB  - Objectives. The primary objective of this study was to determine the relationship
      between waist-to-hip ratio (WHR), cardiovascular (CV) events, and mortality in
      peritoneal dialysis (PD) patients. A secondary objective was to investigate the
      association between abdominal obesity and systemic inflammatory markers. Methods.
      This is a prospective study of 22 prevalent PD patients. WHR was measured at
      baseline. C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-alpha), and
      interleukin-6 (IL-6) were measured. Main outcomes were first CV event and death
      from all causes. Survival analysis was used to examine the relationship between
      anthropomorphic measures and clinical outcomes. Results. Mean follow-up period
      was 3.1 years. In Kaplan-Meier analysis, survival was lower in those with higher
      WHR (P = .002). In Cox regression, WHR independently predicted mortality and
      first CV event after adjustment for known ischemic heart disease (hazard ratio
      [HR] 1.17, confidence interval [CI] 1.05-1.30 for death; HR 1.13, CI 1.01-1.26
      for CV event). WHR correlated with serum TNF-alpha (r = 0.45; P = .05).
      Conclusion. The results of this study suggest WHR may be a risk factor for
      increased CV events and mortality in PD patients. Abdominal obesity is also
      associated with inflammatory markers. Larger studies are warranted to confirm
      these findings.

PMID- 21188242
TI  - Homocysteine is a risk factor in predialysis patients when associated with
      malnutrition and inflammation.
AB  - The increased level of plasma total homocysteine (tHcy) in chronic kidney disease
      patients has been reported as a new and independent risk factor for
      cardiovascular disease. However, after the description of reverse epidemiology in
      the renal population, the association of tHcy and nutrition became less clear. We
      evaluated the association between homocysteine, nutritional status, and
      inflammation, and their impact on mortality in 95 predialysis patients. High
      sensitivity C-Reactive Protein (hs-CRP), interleukin 6 (IL-6), Tumor Necrosis
      Factor alpha (TNF-alpha)], and tHcy were evaluated, as was the nutritional status
      by the modified Subjective Global Nutritional Assessment (mSGA). We divided our
      population in four groups according to their tHcy and mSGA values being above or
      below the mean level and found the lowest survival in the group with tHcy and
      mSGA above the mean level, as well as higher levels of IL-6 (P = .03) and TNF
      alpha (P = .045). Higher levels of homocysteine can be associated with higher
      mortality in predialysis patients, as long as they are associated with
      malnutrition and inflammation.

PMID- 21188243
TI  - Key Role of Human ABC Transporter ABCG2 in Photodynamic Therapy and Photodynamic
      Diagnosis.
AB  - Accumulating evidence indicates that ATP-binding cassette (ABC) transporter ABCG2
      plays a key role in regulating the cellular accumulation of porphyrin derivatives
      in cancer cells and thereby affects the efficacy of photodynamic therapy and
      photodynamic diagnosis. The activity of porphyrin efflux can be affected by
      genetic polymorphisms in the ABCG2 gene. On the other hand, Nrf2, an NF-E2
      related transcription factor, has been shown to be involved in oxidative stress
      mediated induction of the ABCG2 gene. Since patients have demonstrated individual
      differences in their response to photodynamic therapy, transcriptional activation
      and/or genetic polymorphisms of the ABCG2 gene in cancer cells may affect
      patients' responses to photodynamic therapy. Protein kinase inhibitors, including
      imatinib mesylate and gefitinib, are suggested to potentially enhance the
      efficacy of photodynamic therapy by blocking ABCG2-mediated porphyrin efflux from
      cancer cells. This review article provides an overview on the role of human ABC
      transporter ABCG2 in photodynamic therapy and photodynamic diagnosis.

PMID- 21188245
TI  - The Effect of an Aqueous Extract of Teucrium polium on Glutathione Homeostasis In
      Vitro: A Possible Mechanism of Its Hepatoprotectant Action.
AB  - Background. Teucrium polium is used in Arab traditional medicine to treat liver
      diseases. Glutathione is an important intracellular antioxidant, and intrahepatic
      glutathione levels are depleted in liver diseases. Hypothesis and Aim. This
      investigation tested the hypothesis that aqueous extracts of T. polium maintains
      intracellular glutathione levels by augmenting glutathione peroxidase and
      glutathione reductase activity in cultured hepatocytes. Methods. The effects of
      increasing concentrations (0.01-1 mg/mL) of aqueous extract of T. polium were
      assessed in cultured HepG2 cells following 24 hours incubation on (1) cellular
      integrity using (a) the Trypan blue exclusion assay, (b) the [di-methylthiazol
      2yl]-2,5-diphenyl-tetrazoliumbromide (MTT) assay, and (c) the lactate
      dehydrogenase (LDH) assay; (2) glutathione redox state; and (3) glutathione
      peroxidase and glutathione reductase activities using a repeated measures
      experimental design. Results. At concentrations of 0.375 mg/mL and 0.5 mg/mL, the
      extract increased the intracellular levels of total and reduced glutathione and
      had no effect on the intracellular amounts of oxidized glutathione. The extract
      had no effect on glutathione peroxidase and glutathione reductase activities.
      Conclusion. These data indicate that the mechanism of the hepatoprotective action
      of aqueous extracts of T. polium may be, in part, due to augmenting intracellular
      glutathione levels.

PMID- 21188244
TI  - A pharmacological and toxicological profile of silver as an antimicrobial agent
      in medical devices.
AB  - Silver is used widely in wound dressings and medical devices as a broad-spectrum
      antibiotic. Metallic silver and most inorganic silver compounds ionise in
      moisture, body fluids, and secretions to release biologically active Ag(+). The
      ion is absorbed into the systemic circulation from the diet and drinking water,
      by inhalation and through intraparenteral administration. Percutaneous absorption
      of Ag(+) through intact or damaged skin is low. Ag(+) binds strongly to
      metallothionein, albumins, and macroglobulins and is metabolised to all tissues
      other than the brain and the central nervous system. Silver sulphide or silver
      selenide precipitates, bound lysosomally in soft tissues, are inert and not
      associated with an irreversible toxic change. Argyria and argyrosis are the
      principle effects associated with heavy deposition of insoluble silver
      precipitates in the dermis and cornea/conjunctiva. Whilst these changes may be
      profoundly disfiguring and persistent, they are not associated with pathological
      damage in any tissue. The present paper discusses the mechanisms of absorption
      and metabolism of silver in the human body, presumed mechanisms of argyria and
      argyrosis, and the elimination of silver-protein complexes in the bile and urine.
      Minimum blood silver levels consistent with early signs of argyria or argyrosis
      are not known. Silver allergy does occur but the extent of the problem is not
      known. Reference values for silver exposure are discussed.

PMID- 21188246
TI  - The role of tetrahydrobiopterin and dihydrobiopterin in ischemia/reperfusion
      injury when given at reperfusion.
AB  - Reduced nitric oxide (NO) bioavailability and increased oxidative stress are
      major factors mediating ischemia/reperfusion (I/R) injury. Tetrahydrobiopterin
      (BH(4)) is an essential cofactor of endothelial NO synthase (eNOS) to produce NO,
      whereas dihydrobiopterin (BH(2)) can shift the eNOS product profile from NO to
      superoxide, which is further converted to hydrogen peroxide (H(2)O(2)) and cause
      I/R injury. The effects of BH(4) and BH(2) on oxidative stress and postreperfused
      cardiac functions were examined in ex vivo myocardial and in vivo femoral I (20
      min)/R (45 min) models. In femoral I/R, BH(4) increased NO and decreased H(2)O(2)
      releases relative to saline control, and these effects correlated with improved
      postreperfused cardiac function. By contrast, BH(2) decreased NO release relative
      to the saline control, but increased H(2)O(2) release similar to the saline
      control, and these effects correlated with compromised postreperfused cardiac
      function. In conclusion, these results suggest that promoting eNOS coupling to
      produce NO and decrease H(2)O(2) may be a key mechanism to restore postreperfused
      organ function during early reperfusion.

PMID- 21188247
TI  - Blast Induced Brain Injuries - A Grand Challenge in TBI Research.

PMID- 21188248
TI  - Neuro-ophthalmology: through a wide angle lens.

PMID- 21188249
TI  - Challenges for cerebrovascular disease.

PMID- 21188250
TI  - Grand challenges in dementia 2010.

PMID- 21188251
TI  - Potentials of telemedicine for green health care.
AB  - Neurological facilities are traditionally centered in academic hospitals and
      often far away from the patients' living area. Both, the transfer of patients to
      remote hospitals and inpatient treatment are associated with high energy
      consumption. Numbers of patients with neurological diseases are expected to
      increase along with the demographical changes and the environmental impact of
      neurological treatment should become a target for health policy, therefore.
      Positive effects have been demonstrated for the use of telemedicine by improving
      inpatient treatment in local community hospitals or avoiding hospital admissions
      via monitoring of complex diseases in outpatient settings. We discuss the
      potentials of telemedicine in the field of in- and outpatient neurological care
      as well as the need for more scientific evaluation on environmental impacts.

PMID- 21188252
TI  - Challenges for education.

PMID- 21188253
TI  - Frontiers in Endovascular and Interventional Neurology (FEIN): Grand Challenges -
      Looking Ahead.

PMID- 21188254
TI  - Integrative Understanding of Emergent Brain Properties, Quantum Brain Hypotheses,
      and Connectome Alterations in Dementia are Key Challenges to Conquer Alzheimer's
      Disease.
AB  - The biological substrate for cognition remains a challenge as much as defining
      this function of living beings. Here, we examine some of the difficulties to
      understand normal and disordered cognition in humans. We use aspects of
      Alzheimer's disease and related disorders to illustrate how the wealth of
      information at many conceptually separate, even intellectually decoupled,
      physical scales - in particular at the Molecular Neuroscience versus Systems
      Neuroscience/Neuropsychology levels - presents a challenge in terms of true
      interdisciplinary integration towards a coherent understanding. These unresolved
      dilemmas include critically the as yet untested quantum brain hypothesis, and the
      embryonic attempts to develop and define the so-called connectome in humans and
      in non-human models of disease. To mitigate these challenges, we propose a scheme
      incorporating the vast array of scales of the space and time (space-time)
      manifold from at least the subatomic through cognitive-behavioral dimensions of
      inquiry, to achieve a new understanding of both normal and disordered cognition,
      that is essential for a new era of progress in the Generative Sciences and its
      application to translational efforts for disease prevention and treatment.

PMID- 21188256
TI  - Anesthesia and Sedation Practices Among Neurointerventionalists during Acute
      Ischemic Stroke Endovascular Therapy.
AB  - BACKGROUND AND PURPOSE: Intra-arterial reperfusion therapies are expanding
      frontiers in acute ischemic stroke (AIS) management but there is considerable
      variability in clinical practice. The use of general anesthesia (GA) is one
      example. We aimed to better understand sedation practices in AIS. METHODS: An
      online survey was distributed to the 68 active members of the Society of Vascular
      and Interventional Neurology (SVIN). Survey development was based on discussions
      at the SVIN Endovascular Stroke Round Table Meeting (Chicago, IL, 2008). The
      final survey contained 12 questions. Questions were developed as single and
      multiple-item responses; with an option for a free-text response. RESULTS: There
      was a 72% survey response rate (N = 49/68). Respondents were interventional
      neurologists in practice 1-5 years (71.4%, N = 35). The mean (+/-SD) AIS
      interventions performed per year at the respondents' institutions was 42.5 +/-
      25, median 35.0 (IQR 20, 60). The most frequent anesthesia type used was GA
      (anesthesia team), then conscious sedation (nurse administered), monitored
      anesthesia care (anesthesia team), and finally local analgesia alone. There was a
      preference for GA because of eliminating movement (65.3% of respondents; N =
      32/49), perceived procedural safety (59.2%, N = 29/49), and improved procedural
      efficacy (42.9%, N = 21/49). However, cited limitations to GA included risk of
      time delay (69.4%, N = 34), of propagating cerebral ischemia due to hypoperfusion
      or other complications (28.6%, N = 14), and lack of adequate anesthesia workforce
      (20.4%, N = 7). CONCLUSIONS: The most frequent type of anesthesia used by
      Neurointerventionalists for AIS interventions is GA. Prior to making GA standard
      of care during AIS intervention, more data are needed about effects on clinical
      outcomes.

PMID- 21188255
TI  - Comorbidities of migraine.
AB  - Migraine is a common neurological disorder and can be severely disabling during
      attacks. The highest prevalence occurs between the ages of 25 and 55 years,
      potentially the most productive period of life. Migraine leads to a burden not
      only for the individual, but also for the family and society in general. Prior
      studies have found that migraine occurs together with other illnesses at a
      greater coincidental rate than is seen in the general population. These
      occurrences are called "comorbidities," which means that these disorders are
      interrelated with migraine. To delineate the comorbidities of migraine is
      important, because it can help improve treatment strategies and the understanding
      of the possible pathophysiology of migraine. The comorbid illnesses in patients
      with migraine include stroke, sub-clinical vascular brain lesions, coronary heart
      disease, hypertension, patent foramen ovale, psychiatric diseases (depression,
      anxiety, bipolar disorder, panic disorder, and suicide), restless legs syndrome,
      epilepsy and asthma. In this paper, we review the existing epidemiological and
      hospital-based studies, and illustrate the connections between these illnesses
      and migraine.

PMID- 21188257
TI  - Mechanical recanalization of acute carotid terminus occlusion from traumatic
      arterial dissection.
AB  - In the setting of an acute stroke caused by arterial dissection, navigating a
      microcatheter and microguidewire past the dissected artery to gain access to the
      distal thromboembolic lesion may exacerbate the underlying pathology. We review a
      case report whereby successful recanalization of an acute carotid terminus
      occlusion due to intimal-media dissection in the cervical carotid artery
      emphasizing the importance of aggressive proximal guide catheter aspiration in
      conjunction with flow arrest from the carotid bulb proximal to the dissection. We
      discuss the strengths and limitations of this approach and underscore the
      importance of a pathology-based approach to acute stroke therapy.

PMID- 21188258
TI  - Thrombolytic therapy for acute stroke: the hidden dimension.

PMID- 21188259
TI  - A non-anesthetized mouse model for recording sensory urinary bladder activity.
AB  - The goal of this study was to develop an in vivo awake mouse model for
      extracellular bladder sensory nerve recording. A bipolar 125-MUm silver electrode
      was positioned under a single postganglionic bladder nerve. Efferent nerve
      signals were eliminated by tying off the postganglionic bladder nerve between the
      major pelvic ganglion and the recording electrode. Sensory nerve activity was
      measured in the conscious animals 48 h after surgery during continuous
      intravesical infusion of 0.9% saline/0.5% acetic acid followed by 0.5% acetic
      acid with capsazepine (10 MUM) at a rate of 0.75 ml/h. Continuous infusion of
      0.9% NaCl led to a gradual increase in the frequency of sensory nerve firing that
      peaked upon reaching threshold pressure. Non-micturition contractions were
      observed in some animals during filling and other animals exhibited only minimal
      pressure fluctuations; both types of events were associated with a rise in
      sensory nerve activity. Intravesical infusion of 0.5% acetic acid reduced the
      intermicturition interval. This was associated with a 2.1-fold increase in
      bladder pressure during filling and a two-fold increase at both threshold and
      micturition pressures. Concurrent with these changes, sensory activity increased
      2.8-fold during filling and 2.4-fold at threshold pressure. Subsequent
      intravesical infusion of capsazepine in 0.5% acetic acid reduced filling and
      threshold pressures by 21 and 31.2%, respectively, and produced corresponding
      decreases of 36 and 23.4% in sensory nerve activity. The current study shows that
      multifiber sensory nerve recordings can be reproducibly obtained from conscious
      mice.

PMID- 21188260
TI  - Sleep loss in resident physicians: the cause of medical errors?
AB  - This review begins with the history of the events starting with the death of
      Libby Zion that lead to the Bell Commission, that the studied her death and made
      recommendations for improvement that were codified into law in New York state as
      the 405 law that the ACGME essentially adopted in putting a cap on work hours and
      establishing the level of staff supervision that must be available to residents
      in clinical situations particularly the emergency room and acute care units. A
      summary is then provided of the findings of the laboratory effects of total sleep
      deprivation including acute total sleep loss and the consequent widespread
      physiologic alterations, and of the effects of selective and chronic sleep loss.
      Generally the sequence of responses to increasing sleep loss goes from mood
      changes to cognitive effects to performance deficits. In the laboratory
      situation, deficits resulting from sleep deprivation are clearly and definitively
      demonstrable. Sleep loss in the clinical situation is usually sleep deprivation
      superimposed on chronic sleep loss. An examination of questionnaire studies, the
      literature on reports of sleep loss, studies of the reduction of work hours on
      performance as well as observational and a few interventional studies have
      yielded contradictory and often equivocal results. The residents generally find
      they feel better working fewer hours but improvements in patient care are often
      not reported or do not occur. A change in the attitude of the resident toward his
      role and his patient has not been salutary. Decreasing sleep loss should have had
      a positive effect on patient care in reducing medical error, but this remains to
      be unequivocally demonstrated.

PMID- 21188261
TI  - Hyperhomocysteinemia is Associated with Aortic Atheroma Progression in Stroke/TIA
      Patients.
AB  - SIGNIFICANCE: Aortic arch (AA) atheroma and AA atheroma progression are
      independent risk factors for recurrent vascular events in stroke/transient
      ischemic attack (TIA) patients. Total homocysteine level (tHcy) is an independent
      risk marker for atherosclerosis including that found in AA. The purpose of this
      study was to prospectively test the association between AA atheroma progression
      and tHcy. METHODS: This is a cohort study of 307 consecutive hospitalized
      stroke/TIA patients undergoing transesophageal echocardiogram (TEE) as a part of
      their clinical workup. Measurable AA atheroma was detected in 167 patients of
      whom 125 consented to a protocol-mandated follow-up TEE at 12 months. Patients
      had evaluation for vascular risk factors, dietary factors (folate, B12 and
      pyridoxine), and methylene tetrahydrofolate reductase (MTHFR) polymorphism. One
      hundred eighteen stroke/TIA patients had tHcy, acceptable paired AA images, and
      detailed plaque measurements. An increase by >=1 grade of AA atheroma was defined
      as progression. RESULTS: Of the 118 patients, 33 (28%) showed progression and 17
      (14%) showed regression of their index arch lesion at 1 year. tHcy (>=14.0
      MUmol/l) was significantly associated with progression on both univariate (RR =
      3.4, 95% CI 2.0-5.8) and multivariate analyses (adjusted RR = 3.6, 95% CI 2.2
      4.6). The changes in AA plaque thickness (r(2) = 0.11; p < 0.001) and AA plaque
      area (r(2) = 0.08; p = 0.002) correlated with tHcy. tHcy was associated with
      change in plaque thickness over 12 months, independent of age, dietary factors,
      renal function and MTHFR polymorphism (Standardized beta-coefficient 0.335, p =
      0.02). CONCLUSIONS: Our results validate the association and a linear correlation
      between tHcy and progression of AA atheroma.

PMID- 21188263
TI  - Frontiers general neurology grand challenge - a generalist in a specialized
      world.

PMID- 21188262
TI  - The role of fasting versus non-fasting triglycerides in ischemic stroke: a
      systematic review.
AB  - OBJECTIVE: To synthesize results from pertinent studies and determine if fasting
      and/or non-fasting triglycerides are a risk factor for ischemic stroke. METHOD:
      We performed two independent systematic literature searches using the PubMed and
      ScienceDirect databases to identify studies examining the relationship between
      fasting and non-fasting triglyceride concentrations and ischemic stroke risk. A
      meta-analysis was performed using ischemic stroke as a primary endpoint. RESULTS:
      Twenty-five reports were identified, including 13 prospective cohort and 12 case
      control studies. Baseline characteristics, study samples, methods, and primary
      outcomes varied. Of 13 prospective cohort studies, nine assessed triglyceride
      concentrations in the fasting state. Seven of these identified triglycerides as
      an independent risk factor for ischemic stroke risk (n = 1624 ischemic cases).
      Three prospective cohort studies identified a positive association between
      elevated non-fasting triglyceride concentrations and ischemic stroke risk (n =
      2050 ischemic cases). One prospective cohort study that compared fasting and non
      fasting triglycerides identified only non-fasting triglycerides as an independent
      risk factor for ischemic stroke. Of 12 case-control studies identified, five
      identified a positive relationship between ischemic stroke risk and elevated
      fasting triglycerides (n = 838 cases). Seven case-control studies were included
      in the meta-analysis (n = 1996 ischemic stroke cases), revealing an odds ratio of
      1.15 (95% CI, 1.08-1.21). CONCLUSIONS: The available data are inconsistent. The
      relationship between triglyceride levels and ischemic stroke needs further
      investigation under standardized conditions. We recommend a standardized
      triglyceride tolerance test to further investigate the associations between
      fasting versus non-fasting triglyceride levels and ischemic stroke.

PMID- 21188264
TI  - Observations at the CNS-PNS Border of Ventral Roots Connected to a Neuroma.
AB  - Previous studies have shown that numerous sprouts originating from a neuroma,
      after nerve injury in neonatal animals, can invade spinal nerve roots. However,
      no study with a focus on how such sprouts behave when they reach the border
      between the central and peripheral nervous system (CNS-PNS border) has been
      published. In this study we have in detail examined the CNS-PNS border of ventral
      roots in kittens with light and electron microscopy after early postnatal sciatic
      nerve resection. A transient ingrowth of substance P positive axons was observed
      into the CNS, but no spouts remained 6 weeks after the injury. Using serial
      sections and electron microscopy it was possible to identify small bundles of
      unmyelinated axons that penetrated from the root fascicles for a short distance
      into the CNS. These axons ended blindly, sometimes with a growth cone-like
      terminal swelling filled with vesicles. The axon bundles were accompanied by p75
      positive cells in both the root fascicles and the pia mater, but not in the CNS.
      It may thus be suggested that neurotrophin presenting p75 positive cells could
      facilitate axonal growth into the pia mater and that the lack of such cells in
      the CNS compartment might contribute to the failure of growth into the CNS. A
      maldevelopment of myelin sheaths at the CNS-PNS border of motor axons was
      observed and it seems possible that this could have consequences for the
      propagation of action potential across this region after neonatal nerve injury.
      Thus, in this first detailed study on the behavior of recurrent sprouts at the
      CNS-PNS border.

PMID- 21188265
TI  - Timing of sleep and its relationship with the endogenous melatonin rhythm.
AB  - While much research has investigated the effects of exogenous melatonin on sleep,
      less is known about the relationship between the timing of the endogenous
      melatonin rhythm and the sleep-wake cycle. Significant inter-individual
      variability in the phase relationship between sleep and melatonin rhythms has
      been reported although the extent to which the variability reflects intrinsic
      and/or environmental differences is unknown. We examined the effects of different
      sleeping schedules on the time of dim light melatonin onset (DLMO) in 28 young,
      healthy adults. Participants chose to maintain either an early (22:30-06:30 h) or
      a late (00:30-08:30 h) sleep schedule for at least 3 weeks prior to an overnight
      laboratory visit. Saliva samples were collected under dim light (<2 lux) and
      controlled posture conditions to determine salivary DLMO. The 2-h difference
      between groups in the enforced sleep-wake schedule was associated with a
      concomitant 1.75-h delay in DLMO. The mean phase relationship between sleep onset
      and DLMO remained constant (~2 h). The variance in DLMO time, however, was
      greater in the late group (range 4.5 h) compared to the early group (range 2.4 h)
      perhaps due to greater effect of environmental influences in delayed sleep types
      or greater intrinsic instability in their circadian system. The findings
      contribute to our understanding of individual differences in the human circadian
      clock and have important implications for the diagnosis and treatment of
      circadian rhythm sleep disorders, in particular if a greater normative range for
      phase angle of entrainment occurs in individuals with later sleep-wake schedules.

PMID- 21188266
TI  - Thrombolysis for cerebral ischemia.
AB  - The care for patients with acute ischemic stroke has been revolutionized by the
      clinical application of fibrinolysis. Intravenous recombinant tissue plasminogen
      activator (rt-PA) has been proven to improve functional outcomes following acute
      ischemic stroke and can be administered to a select group of patients up to 4.5 h
      after symptom onset. Time from symptom onset to thrombolysis is the most
      important determinant of the success of treatment, with greatest efficacy if
      given within 90 min. Hospitals should implement standardized processes and
      protocols for acute stroke to guide immediate patient assessment, brain imaging,
      drug administration, and post-thrombolysis care. In this article we review the
      clinical application of thrombolysis, care of acute stroke patients, current
      evidence regarding fibrinolysis, and future direction of penumbral imaging to
      select candidates for reperfusion therapies.

PMID- 21188267
TI  - The fourth element targeting hypothesis of Alzheimer's disease pathogenesis and
      pathophysiology.
AB  - Despite well over a century of research on all forms of the disorder known as
      Alzheimer's disease (AD), it is still not known whether the condition targets
      initially neurons, glial cells, other cellular elements in the brain, or
      components of cells, such as synapses, or molecules independently of their
      cellular compartmentalization, or otherwise (e.g., specific neuronal circuits).
      Multiple lines of highly suggestive but as yet insufficient experimental evidence
      are discussed here to formulate the hypothesis that AD results from primary
      (i.e., direct and initial) or secondary targeting of what we designate as the
      Fourth Element Cell (4EC): a relatively recently identified type of brain cell
      that exhibits features in common with neurons (e.g., synapses, participation in
      glutamatergic, and GABAergic neurotransmission), astrocytes, oligodendrocytes,
      and their precursors, but is in other respects clearly distinct from all of them.
      The 4EC is proposed to be the main target of both: (1) converging insults (i.e.,
      not true "causes") that over time cause sporadic forms of AD as postulated by the
      Danger Signal Hypothesis - which was not formulated with 4EC in mind - as well as
      (2) the causes of inherited (i.e., familial) forms of neurodegeneration that
      resemble certain aspects of the clinical manifestations of sporadic AD.

PMID- 21188268
TI  - Vasculopathic cranial ocular motor neuropathy following sudden emotional stress.
AB  - We describe three patients who experienced onset of a microvascular ocular motor
      nerve palsy in the setting of sudden emotional stress. Such emotional states are
      accompanied by a marked increase in sympathetic tone in some individuals.
      Mechanisms by which these autonomic changes might produce an ischemic cranial
      nerve palsy include intra-cranial vasoconstriction and transient systemic
      hypotension due to alterations in cardiac function.

PMID- 21188270
TI  - Triglycerides and stroke risk prediction: lessons from a prospective cohort study
      in german primary care patients.

PMID- 21188269
TI  - The disturbance of gaze in progressive supranuclear palsy: implications for
      pathogenesis.
AB  - Progressive supranuclear palsy (PSP) is a disease of later life that is currently
      regarded as a form of neurodegenerative tauopathy. Disturbance of gaze is a
      cardinal clinical feature of PSP that often helps clinicians to establish the
      diagnosis. Since the neurobiology of gaze control is now well understood, it is
      possible to use eye movements as investigational tools to understand aspects of
      the pathogenesis of PSP. In this review, we summarize each disorder of gaze
      control that occurs in PSP, drawing on our studies of 50 patients, and on reports
      from other laboratories that have measured the disturbances of eye movements.
      When these gaze disorders are approached by considering each functional class of
      eye movements and its neurobiological basis, a distinct pattern of eye movement
      deficits emerges that provides insight into the pathogenesis of PSP. Although
      some aspects of all forms of eye movements are affected in PSP, the predominant
      defects concern vertical saccades (slow and hypometric, both up and down),
      impaired vergence, and inability to modulate the linear vestibulo-ocular reflex
      appropriately for viewing distance. These vertical and vergence eye movements
      habitually work in concert to enable visuomotor skills that are important during
      locomotion with the hands free. Taken with the prominent early feature of falls,
      these findings suggest that PSP tauopathy impairs a recently evolved neural
      system concerned with bipedal locomotion in an erect posture and frequent gaze
      shifts between the distant environment and proximate hands. This approach
      provides a conceptual framework that can be used to address the nosological
      challenge posed by overlapping clinical and neuropathological features of
      neurodegenerative tauopathies.

PMID- 21188271
TI  - Characterization of the vagal motor neurons projecting to the Guinea pig airways
      and esophagus.
AB  - Distinct parasympathetic postganglionic neurons mediate contractions and
      relaxations of the guinea pig airways. We set out to characterize the vagal
      inputs that regulate contractile and relaxant airway parasympathetic
      postganglionic neurons. Single and dual retrograde neuronal tracing from the
      airways and esophagus revealed that distinct, but intermingled, subsets of
      neurons in the compact formation of the nucleus ambiguus (nAmb) innervate these
      two tissues. Tracheal and esophageal neurons identified in the nAmb were
      cholinergic. Esophageal projecting neurons also preferentially (greater than 70%)
      expressed the neuropeptide CGRP, but could not otherwise be distinguished
      immunohistochemically from tracheal projecting preganglionic neurons. Few
      tracheal or esophageal neurons were located in the dorsal motor nucleus of the
      vagus. Electrical stimulation of the vagi in vitro elicited stimulus dependent
      tracheal and esophageal contractions and tracheal relaxations. The voltage
      required to evoke tracheal smooth muscle relaxation was significantly higher than
      that required for evoking either tracheal contractions or esophageal longitudinal
      striated muscle contractions. Together our data support the hypothesis that
      distinct vagal preganglionic pathways regulate airway contractile and relaxant
      postganglionic neurons. The relaxant preganglionic neurons can also be
      differentiated from the vagal motor neurons that innervate the esophageal
      striated muscle.

PMID- 21188272
TI  - The Role of Electrical Pacemakers in the Treatment of Unexpected Cardiac Arrest.

PMID- 21188273
TI  - Refining Intervention Targets in Family-Based Research: Lessons From Quantitative
      Behavioral Genetics.
AB  - The results from a large body of family-based research studies indicate that
      modifying the environment (specifically dimensions of the social environment)
      through intervention is an effective mechanism for achieving positive outcomes.
      Parallel to this work is a growing body of evidence from genetically informed
      studies indicating that social environmental factors are central to enhancing or
      offsetting genetic influences. Increased precision in the understanding of the
      role of the social environment in offsetting genetic risk might provide new
      information about environmental mechanisms that could be applied to prevention
      science. However, at present, the multifaceted conceptualization of the
      environment in prevention science is mismatched with the more limited measurement
      of the environment in many genetically informed studies. In this article, we
      present a framework for translating quantitative behavioral genetic research to
      inform the development of preventive interventions. The measurement of
      environmental indices amenable to modification is discussed within the context of
      quantitative behavioral genetic studies. In particular, emphasis is placed on the
      necessary elements that lead to benefits in prevention science, specifically the
      development of evidence-based interventions. We provide an example from an
      ongoing prospective adoption study to illustrate the potential of this
      translational process to inform the selection of preventive intervention targets.

PMID- 21188274
TI  - An update in management of noncutaneous T-cell lymphomas.
AB  - T-cell lymphoma is a heterogeneous group of diseases. Except for ALK positive
      anaplastic large cell lymphoma, T-cell lymphoma responds to conventional
      chemotherapy unfavourably, and most patients carry poor prognosis. In recent
      years, efforts have been made to improve the outcome of T-cell lymphoma patients.
      Novel agents, high-dose therapy, and allogeneic stem cell transplantation are
      studied, and various results are reported in literature. This paper looks into
      the prognostication and treatment approach of different entities of noncutaneous
      T-cell lymphoma and would focus on the latest updates in its management.

PMID- 21188275
TI  - Hippocampal testosterone relates to reference memory performance and synaptic
      plasticity in male rats.
AB  - Steroids are important neuromodulators influencing cognitive performance and
      synaptic plasticity. While the majority of literature concerns adrenal- and
      gonadectomized animals, very little is known about the "natural" endogenous
      release of hormones during learning. Therefore, we measured blood and brain
      (hippocampus, prefrontal cortex) testosterone, estradiol, and corticosterone
      concentrations of intact male rats undergoing a spatial learning paradigm which
      is known to reinforce hippocampal plasticity. We found significant modulations of
      all investigated hormones over the training course. Corticosterone and
      testosterone were correlated manifold with behavior, while estradiol expressed
      fewer correlations. In the recall session, testosterone was tightly coupled to
      reference memory (RM) performance, which is crucial for reinforcement of synaptic
      plasticity in the dentate gyrus. Intriguingly, prefrontal cortex and hippocampal
      levels related differentially to RM performance. Correlations of testosterone and
      corticosterone switched from unspecific activity to specific cognitive functions
      over training. Correspondingly, exogenous application of testosterone revealed
      different effects on synaptic and neuronal plasticity in trained versus untrained
      animals. While hippocampal long-term potentiation (LTP) of the field excitatory
      postsynaptic potential (fEPSP) was prolonged in untrained rats, both the fEPSP-
      and the population spike amplitude (PSA)-LTP was impaired in trained rats.
      Behavioral performance was unaffected, but correlations of hippocampal field
      potentials with behavior were decoupled in treated rats. The data provide
      important evidence that besides adrenal, also gonadal steroids play a mechanistic
      role in linking synaptic plasticity to cognitive performance.

PMID- 21188277
TI  - Immunosuppression and Neoplasia.
AB  - This entire session is based upon a fairly simple assumption that the state of
      the host immune system is an important factor in determining whether or not
      malignant tumors develop and/or with what aggressiveness the tumors grow and
      spread after their inception. The objective of the presentation is to report to
      you some observations that quite definitely support an immunologic hypothesis for
      the etiology of cancer.

PMID- 21188276
TI  - Ivabradine reduces chemokine-induced CD4-positive lymphocyte migration.
AB  - AIMS: Migration of CD4-positive lymphocytes into the vessel wall is a critical
      step in atherogenesis. Recent data suggest that ivabradine, a selective I(f)
      channel blocker, reduces atherosclerotic plaque formation in apolipoprotein E
      deficient mice, hitherto nothing is known about the mechanism by which ivabradine
      modulates plaque formation. Therefore, the present study investigated whether
      ivabradine regulates chemokine-induced migration of lymphocytes. METHODS AND
      RESULTS: Stimulation of CD4-positive lymphocytes with SDF-1 leads to a 2.0 +/-
      0.1 fold increase in cell migration (P < .01; n = 7). Pretreatment of cells with
      ivabradine reduces this effect to a maximal 1.2 +/- 0.1 fold induction at 0.1
      umol/L ivabradine (P < .01 compared to SDF-1-treated cells, n = 7). The effect of
      ivabradine on CD4-positive lymphocyte migration was mediated through an early
      inhibition of chemokine-induced PI-3 kinase activity as determined by PI-3 kinase
      activity assays. Downstream, ivabradine inhibits activation of the small GTPase
      Rac and phosphorylation of the Myosin Light Chain (MLC). Moreover, ivabradine
      treatment reduces f-actin formation as well as ICAM3 translocation to the uropod
      of the cell, thus interfering with two important steps in T cell migration.
      CONCLUSION: Ivabradine inhibits chemokine-induced migration of CD4-positive
      lymphocytes. Given the crucial importance of chemokine-induced T-cell migration
      in early atherogenesis, ivabradine may be a promising tool to modulate this
      effect.

PMID- 21188278
TI  - Hepatic Homograft Survival in Pediatric Orthotopic Liver Transplantation with
      Cyclosporine and Steroids.

PMID- 21188279
TI  - Production of a Standardized Anti-Lymphocyte Globulin.

PMID- 21188280
TI  - Feasibility and Acceptability of an English-as-a-Second Language Curriculum on
      Hepatitis B for Older Chinese American Immigrants.
AB  - Asian immigrants to the U.S. have an increased prevalence of hepatitis B virus
      (HBV) infection compared to native born individuals; an estimated 10 percent of
      Chinese immigrants are infected with HBV. Using qualitative data from focus
      groups, we developed an English-as-a-Second Language (ESL) curriculum that aimed
      to improve knowledge about key hepatitis B facts. The curriculum was pilot-tested
      among 56 students aged 50 and older from intermediate-level ESL classes at a
      community-based organization that serves Chinese immigrants. Post-curriculum data
      showed increases in knowledge that hepatitis B can cause liver cancer (73% at pre
      test vs. 91% at post-test; p value = 0.01) and that individuals can be infected
      with hepatitis B for life (34% vs. 81%; p value <0.0001). These findings suggest
      that an ESL curriculum can successfully improve knowledge about the severity of
      hepatitis B and its routes of transmission among older Chinese American adults.

PMID- 21188281
TI  - Alcohol Messages in Prime-Time Television Series.
AB  - Alcohol messages contained in television programming serve as sources of
      information about drinking. To better understand the ways embedded messages about
      alcohol are communicated, it is crucial to objectively monitor and analyze
      television alcohol depictions. This article presents a content analysis of an
      eight-week sample of eighteen prime-time programs. Alcohol messages were coded
      based on modalities of presentation, level of plot connection, and valence. The
      analysis reveals that mixed messages about alcohol often coexist but the ways in
      which they are presented differ: whereas negative messages are tied to the plot
      and communicated verbally, positive messages are associated with subtle visual
      portrayals.

PMID- 21188282
TI  - Conscious Awareness and the Brain Processing.
AB  - The study of consciousness has been limited primarily to philosophical domain.
      There are a number of conceptual and methodological issues that have prevented
      scientific investigation of conscious experience. We began the investigation by
      exploring its cognitive components. Since awareness is an important component, we
      used neuroimaging techniques to study the brain processing of awareness using
      memory as a model. It is known that in the tests of 'nonconscious memory'
      subjects retrieve studied items without becoming consciously aware of retrieval.
      In contrast, they are fully aware in conscious memory tests. Spatial and temporal
      patterns of cortical activities observed during the two forms of memory were
      analyzed to understand neural network that might be associated with the awareness
      of retrieval. It appears that during conscious recollection, studied items are
      first retrieved nonconsciously. Thereafter, a reentrant signaling loop is
      activated between the extrastriate area and frontal cortex. Experiments suggest
      that this loop may be responsible for the awareness of nonconsciously retrieved
      information. Further characterization of the extrastriate-frontal connectivity
      may help explain the neural mechanism of conscious experience.

PMID- 21188283
TI  - Exposure to Alcohol Use in Movies: Future Directions.

PMID- 21188284
TI  - Classifying Facial Actions.
AB  - The Facial Action Coding System (FACS) [23] is an objective method for
      quantifying facial movement in terms of component actions. This system is widely
      used in behavioral investigations of emotion, cognitive processes, and social
      interaction. The coding is presently performed by highly trained human experts.
      This paper explores and compares techniques for automatically recognizing facial
      actions in sequences of images. These techniques include analysis of facial
      motion through estimation of optical flow; holistic spatial analysis, such as
      principal component analysis, independent component analysis, local feature
      analysis, and linear discriminant analysis; and methods based on the outputs of
      local filters, such as Gabor wavelet representations and local principal
      components. Performance of these systems is compared to naive and expert human
      subjects. Best performances were obtained using the Gabor wavelet representation
      and the independent component representation, both of which achieved 96 percent
      accuracy for classifying 12 facial actions of the upper and lower face. The
      results provide converging evidence for the importance of using local filters,
      high spatial frequencies, and statistical independence for classifying facial
      actions.

PMID- 21188285
TI  - A Cross-species Comparison of Facial Morphology and Movement in Humans and
      Chimpanzees Using the Facial Action Coding System (FACS).
AB  - A comparative perspective has remained central to the study of human facial
      expressions since Darwin's [(1872/1998). The expression of the emotions in man
      and animals (3rd ed.). New York: Oxford University Press] insightful observations
      on the presence and significance of cross-species continuities and species-unique
      phenomena. However, cross-species comparisons are often difficult to draw due to
      methodological limitations. We report the application of a common methodology,
      the Facial Action Coding System (FACS) to examine facial movement across two
      species of hominoids, namely humans and chimpanzees. FACS [Ekman & Friesen
      (1978). Facial action coding system. CA: Consulting Psychology Press] has been
      employed to identify the repertoire of human facial movements. We demonstrate
      that FACS can be applied to other species, but highlight that any modifications
      must be based on both underlying anatomy and detailed observational analysis of
      movements. Here we describe the ChimpFACS and use it to compare the repertoire of
      facial movement in chimpanzees and humans. While the underlying mimetic
      musculature shows minimal differences, important differences in facial morphology
      impact upon the identification and detection of related surface appearance
      changes across these two species.

PMID- 21188286
TI  - Neural correlates of verbal associative memory and mnemonic strategy use
      following childhood traumatic brain injury.
AB  - Children with traumatic brain injury (TBI) often experience memory deficits,
      although the nature, functional implication, and recovery trajectory of such
      difficulties are poorly understood. The present fMRI study examined the neural
      activation patterns in a group of young children who sustained moderate TBI in
      early childhood (n = 7), and a group of healthy control children (n = 13) during
      a verbal paired associate learning (PAL) task that promoted the use of two
      mnemonic strategies differing in efficacy. The children with TBI demonstrated
      intact memory performance and were able to successfully utilize the mnemonic
      strategies. However, the TBI group also demonstrated altered brain activation
      patterns during the task compared to the control children. These findings suggest
      early childhood TBI may alter activation within the network of brain regions
      supporting associative memory even in children who show good behavioral
      performance.

PMID- 21188287
TI  - Primary Amine-Catalyzed Biginelli Reaction for the Enantioselective Synthesis of
      3,4-Dihydropyrimidin-2(1H)-ones.
AB  - Several chiral primary amines, mainly those derived from the cinchona alkaloids,
      were evaluated as the organocatalysts for the asymmetric Biginelli reaction. With
      the quinine-derived amine catalyst 1 and after extensive optimization of the
      reaction conditions, 3,4-dihydropyrimidin-2(1H)-ones were obtained in moderate to
      good yields and 51-78% ee from a three-component reaction of aryl and aliphatic
      aldehydes, urea, and acetoacetate.

PMID- 21188288
TI  - SIGNAL REGULARITY-BASED AUTOMATED SEIZURE DETECTION SYSTEM FOR SCALP EEG
      MONITORING.
AB  - The purpose of the present study was to build a clinically useful automated
      seizure detection system for scalp EEG recordings. To achieve this, a computer
      algorithm was designed to translate complex multichannel scalp EEG signals into
      several dynamical descriptors, followed by the investigations of their
      spatiotemporal properties that relate to the ictal (seizure) EEG patterns as well
      as to normal physiologic and artifact signals. This paper describes in detail
      this novel seizure detection algorithm and reports its performance in a large
      clinical dataset.

PMID- 21188289
TI  - AMIDE FORMATION BY DECARBOXYLATIVE CONDENSATION OF HYDROXYLAMINES AND alpha
      KETOACIDS: N-[(1S)-1 PHENYLETHYL]-BENZENEACETAMIDE.

PMID- 21188290
TI  - An Analysis of the Causes of Death After Pediatric Liver Transplantation.

PMID- 21188292
TI  - Clinical Experience with ALG.

PMID- 21188291
TI  - Chimerism after Whole Organ Transplant.

PMID- 21188293
TI  - The treatment of penetrating wounds of the inferior vena cava.

PMID- 21188294
TI  - What Goes Wrong during Passive Sentence Production in Agrammatic Aphasia: An
      Eyetracking Study.
AB  - BACKGROUND: Production of passive sentences is often impaired in agrammatic
      aphasia and has been attributed both to an underlying structural impairment
      (e.g., Schwartz, Saffran, Fink, Myers, & Martin, 1994) and to a morphological
      deficit (e.g., Caplan & Hanna, 1998; Faroqi-Shah & Thompson, 2003). However, the
      nature of the deficit in passive sentence production is not clear due to
      methodological issues present in previous studies.  AIMS: This study examined
      active and passive sentence production in nine agrammatic aphasic speakers under
      conditions of structural priming using eyetracking to test whether structural
      impairments occur independently of morphological impairments and whether the
      underlying nature of error types is reflected in on-line measures, i.e., eye
      movements and speech onset latencies.  METHODS #ENTITYSTARTX00026; PROCEDURES:
      Nine participants viewed and listened to a prime sentence in either active or
      passive voice, and then repeated it aloud. Next, a target picture appeared on the
      computer monitor and participants were instructed to describe it using the primed
      sentence structure.  OUTCOMES #ENTITYSTARTX00026; RESULTS: Participants made
      substantial errors in sentence structure, i.e., passives with role reversals
      (RRs) and actives-for-passives, but few errors in passive morphology. Longer gaze
      durations to the first-produced noun for passives with RRs as compared to correct
      passives were found before and during speech. For actives-for-passives, however,
      this pattern was found during speech, but not before speech.  CONCLUSIONS: The
      deficit in passive sentence production does not solely arise from a morphological
      deficit, rather it stems, at least in part, from a structural level impairment.
      The underlying nature of passives with RRs is qualitatively different from that
      of actives-for-passives, which cannot be clearly differentiated with off-line
      testing methodology.

PMID- 21188295
TI  - THE USE OF COMBINED PRESERVATION TECHNIQUES FOR EXTENDED STORAGE OF ORTHOTOPIC
      LIVER HOMOGRAFTS.

PMID- 21188296
TI  - Piezo- and Flexoelectric Membrane Materials Underlie Fast Biological Motors in
      the Ear.
AB  - The mammalian inner ear is remarkably sensitive to quiet sounds, exhibits over
      100dB dynamic range, and has the exquisite ability to discriminate closely spaced
      tones even in the presence of noise. This performance is achieved, in part,
      through active mechanical amplification of vibrations by sensory hair cells
      within the inner ear. All hair cells are endowed with a bundle of motile
      microvilli, stereocilia, located at the apical end of the cell, and the more
      specialized outer hair cells (OHC's) are also endowed with somatic
      electromotility responsible for changes in cell length in response to
      perturbations in membrane potential. Both hair bundle and somatic motors are
      known to feed energy into the mechanical vibrations in the inner ear. The
      biophysical origin and relative significance of the motors remains a subject of
      intense research. Several biological motors have been identified in hair cells
      that might underlie the motor(s), including a cousin of the classical ATP driven
      actin-myosin motor found in skeletal muscle. Hydrolysis of ATP, however, is much
      too slow to be viable at audio frequencies on a cycle-by-cycle basis.
      Heuristically, the OHC somatic motor behaves as if the OHC lateral wall membrane
      were a piezoelectric material and the hair bundle motor behaves as if the plasma
      membrane were a flexoelectric material. We propose these observations from a
      continuum materials perspective are literally true. To examine this idea, we
      formulated mathematical models of the OHC lateral wall "piezoelectric" motor and
      the more ubiquitous "flexoelectric" hair bundle motor. Plausible biophysical
      mechanisms underlying piezo- and flexoelectricity were established. Model
      predictions were compared extensively to the available data. The models were then
      applied to study the power conversion efficiency of the motors. Results show that
      the material properties of the complex membranes in hair cells provide them with
      the ability to convert electrical power available in the inner ear cochlea into
      useful mechanical amplification of sound induced vibrations at auditory
      frequencies. We also examined how hair cell amplification might be controlled by
      the brain through efferent synaptic contacts on hair cells and found a simple
      mechanism to tune hearing to signals of interest to the listener by electrical
      control of these motors.

PMID- 21188297
TI  - Identification of the Aldehydic Metabolites.

PMID- 21188298
TI  - EFFECT OF CYCLOSPORIN ON HEPATIC REGENERATION.

PMID- 21188299
TI  - THE PROBLEMS AND PROGNOSIS OF THE CHRONICALLY SURVIVING PATIENT AFTER RENAL
      HOMOTRANSPLANTATION.

PMID- 21188300
TI  - Geographical and climatic limits of needle types of one- and two-needled pinyon
      pines.
AB  - AIM: The geographical extent and climatic tolerances of one- and two-needled
      pinyon pines (Pinus subsect. Cembroides) are the focus of questions in taxonomy,
      palaeoclimatology and modelling of future distributions. The identification of
      these pines, traditionally classified by one- versus two-needled fascicles, is
      complicated by populations with both one- and two-needled fascicles on the same
      tree, and the description of two more recently described one-needled varieties:
      the fallax-type and californiarum-type. Because previous studies have suggested
      correlations between needle anatomy and climate, including anatomical plasticity
      reflecting annual precipitation, we approached this study at the level of the
      anatomy of individual pine needles rather than species. LOCATION: Western North
      America. METHODS: We synthesized available and new data from field and herbarium
      collections of needles to compile maps of their current distributions across
      western North America. Annual frequencies of needle types were compared with
      local precipitation histories for some stands. Historical North American climates
      were modelled on a c. 1-km grid using monthly temperature and precipitation
      values. A geospatial model (ClimLim), which analyses the effect of climate
      modulated physiological and ecosystem processes, was used to rank the importance
      of seasonal climate variables in limiting the distributions of anatomical needle
      types. RESULTS: The pinyon needles were classified into four distinct types based
      upon the number of needles per fascicle, needle thickness and the number of
      stomatal rows and resin canals. The individual needles fit well into four
      categories of needle types, whereas some trees exhibit a mixture of two needle
      types. Trees from central Arizona containing a mixture of Pinus edulis and fallax
      type needles increased their percentage of fallax-type needles following dry
      years. All four needle types occupy broader geographical regions with distinctive
      precipitation regimes. Pinus monophylla and californiarum-type needles occur in
      regions with high winter precipitation. Pinus edulis and fallax-type needles are
      found in regions with high monsoon precipitation. Areas supporting californiarum
      type and fallax-type needle distributions are additionally characterized by a
      more extreme May-June drought. MAIN CONCLUSIONS: These pinyon needle types seem
      to reflect the amount and seasonality of precipitation. The single needle
      fascicle characterizing the fallax type may be an adaptation to early summer or
      periodic drought, while the single needle of Pinus monophylla may be an
      adaptation to summer-autumn drought. Although the needles fit into four distinct
      categories, the parent trees are sometimes less easily classified, especially
      near their ancestral Pleistocene ranges in the Mojave and northern Sonoran
      deserts. The abundance of trees with both one- and two-needled fascicles in the
      zones between P. monophylla, P. edulis and fallax-type populations suggest that
      needle fascicle number is an unreliable characteristic for species
      classification. Disregarding needle fascicle number, the fallax-type needles are
      nearly identical to P. edulis, supporting Little's (1968) initial classification
      of these trees as P. edulis var. fallax, while the californiarum-type needles
      have a distinctive morphology supporting Bailey's (1987) classification of this
      tree as Pinus californiarum.

PMID- 21188301
TI  - Adolescence as risk factor for adverse pregnancy outcome in Central Africa--a
      cross-sectional study.
AB  - BACKGROUND: Sub-Saharan Africa has the highest rates of maternal and neonatal
      mortality worldwide. Young maternal age at delivery has been proposed as risk
      factor for adverse pregnancy outcome, yet there is insufficient data from Sub
      Saharan Africa. The present study aimed to investigate the influence of maternal
      adolescence on pregnancy outcomes in the Central African country Gabon.
      METHODOLOGY AND PRINCIPAL FINDINGS: Data on maternal age, parity, birth weight,
      gestational age, maternal Plasmodium falciparum infection, use of bednets, and
      intake of intermittent preventive treatment of malaria in pregnancy were
      collected in a cross-sectional survey in 775 women giving birth in three mother
      child health centers in Gabon. Adolescent women (<=16 years of age) had a
      significantly increased risk to deliver a baby with low birth weight in
      univariable analysis (22.8%, 13/57, vs. 9.3%, 67/718, OR: 2.9, 95% CI: 1.5-5.6)
      and young maternal age showed a statistically significant association with the
      risk for low birth weight in multivariable regression analysis after correction
      for established risk factors (OR: 2.7; 95% CI: 1.1-6.5). In further analysis
      adolescent women were shown to attend significantly less antenatal care visits
      than adult mothers (3.3+/-1.9 versus 4.4+/-1.9 mean visits, p<0.01, n = 356) and
      this difference accounted at least for part of the excess risk for low birth
      weight in adolescents. CONCLUSION: Our data demonstrate the importance of
      adolescent age as risk factor for adverse pregnancy outcome. Antenatal care
      programs specifically tailored for the needs of adolescents may be necessary to
      improve the frequency of antenatal care visits and pregnancy outcomes in this
      risk group in Central Africa.

PMID- 21188302
TI  - [Pubertal behavioral decompensation in patients with pervasive developmental
      disorders].
AB  - OBJECTIVES: To describe behavioral descompensation in adolescents with autistic
      spectrum disorders (ASD). METHODS: We analyzed in a prospective study the stories
      of 11 children and adolescents with ASD, their demographic characteristics,
      initial symptoms of descompensation at pubertal or adolescence stages,
      interventions developed and evolution with them. RESULTS: We studied the clinical
      stories of eleven patients, 8 men and 3 women, who consulted with behavioral
      descompensation periods at a mean age of 13 years (range 10- 16 years). They
      presented with hyperactivity/agitation (6), injuries and aggression against
      others or themselves (6), irritability/ emotional labiality (6), inappropriate
      shouting (6), inflexibility/ rituals (4) and catatonia (2). Almost all patients
      had received psychiatric medication before descompensation, except patients with
      catatonia. Four of 11 presented two episodes and seven patients only one episode
      during a period of 2.7 years of follow-up (range 1- 6 years). Eight of 11
      patients recovered with psychological and pharmacological (a medium of 2 drugs)
      interventions in a mean time of 4 months. Both patients with catatonia didn't
      recovered, and one more patient didn't improved with pharmacological treatment.
      CONCLUSIONS: Behavioral descompensations are very frequent complications in
      patients with autism at puberty or adolescence stages. Most of them recover with
      very close combined interventions and familial support.

PMID- 21188303
TI  - [Training in the detection of bipolar disorders for psychologists and primary
      health agents: a pilot study].
AB  - OBJECTIVES: At present, Bipolar Disorders are considered a real public health
      problem. There is an agreement that it is a priority to solve the existent flaws
      as regards the certainty of a correct and timely diagnosis of these disorders.
      This paper report the results of a pilot experience in workshops of training in
      the detection of Bipolar Disorders aimed at psychologists and primary health
      agents. METHOD: A survey was carried out before and after the training sessions
      with the aim of measuring prior knowledge about bipolar disorders and thus
      evaluating the impact of the training workshops. RESULTS: 227 people completed
      the surveys. The results showed a scarce knowledge about these disorders, even
      among those professionals who acknowledged having bipolar patients in treatment
      and who had interest in being trained. On the other hand, these surveys revealed
      significant changes in their knowledge of bipolar disorders. CONCLUSION: This
      pilot experience suggests that with low cost events such as the organized
      workshops it would be possible to increase the ability of timely detection of
      bipolar disorders in the key agents of the health system. Reducing frequents
      delays and mistakes in the diagnosis of these disorders which would determine a
      significant reduction in their morbid impact.

PMID- 21188304
TI  - [Notes regarding the epistemological analysis of some problems in contemporary
      psychiatry].
AB  - The paper has two parts. The first part offers a general presentation of
      Epistemology and its main currents. The second part explores an analysis of some
      problems in contemporary psychiatry from an epistemological viewpoint.

PMID- 21188305
TI  - [The evolution of the borderline personality disorder diagnosis: past, present
      and future].
AB  - The purpose of this paper is to go along the different senses and meanings that
      borderline diagnosis has had across time. On behalf of this, many original papers
      as well as textbooks and other works are analyzed, to define the way and
      significant points in the discovery or construction of this critical pathology,
      that even today still divides the opinions in health world community. From
      Prichard, to Stern, Deutsch, Grinker and Knight, till Kernberg, Gunderson,
      Linehan and Fonagy we try to put clear the most important contributions of each
      author.

PMID- 21188306
TI  - [The differential diagnosis of hysteria in the ravines of contemporary
      psychiatry].
AB  - The diagnosis of "hysteria" has recently become part of the history of
      Psychiatry. Although fully trained dynamic psychiatrists, followers of
      psychoanalytic theories, still make use of some clinical and theoretical
      production upon hysteria, for many of the young psychiatrists this term has
      disappeared from their scope. They only know of dissociative disorders,
      somatoform disorders and histrionic personality disorders, or they rather
      distinguish other diagnosis with which hysteria could be mistaken for. Despite
      the diagnosis of hysteria has been removed from the DSM, the difficulties these
      patients frequently imposed to physicians still prevail.

PMID- 21188307
TI  - [Differential diagnosis between borderline personality disorder and bipolar
      disorder].
AB  - The relationship between bipolar disorder and borderline personality disorder
      remains controversial since in both conditions there are overlapping and similar
      symptomatic dimensions. Symptomatic dimensions suitable to subserve differential
      diagnosis are: mood, mood variability mode, and personal and family history.
      Characteristics of psychotic symptoms may also be useful in the differentiation.
      On the other hand, anxiety symptoms, neuropsychological profiles, neuro-imaging
      procedures and biomarkers seem not to contribute to differentiate between both
      diseases. The presentation of nonsuicidal self mutilation behavior can offer some
      differences between bipolar and borderline personality disorders, but both can
      coexist in clinical comorbid forms and do not significantly contribute to the
      differential diagnosis. Differential diagnosis is complicated by the fact that a
      low percentage of patients can experience comorbidity of both conditions. In this
      work we review all these issues, and particularly emphasize the importance of
      sitematically take into account the patient background, the course that follows
      his or her disorder, together with the outcome in response to medical decisions.

PMID- 21188308
TI  - [Disinhibition in psychogeriatry: differential diagnosis with frontotemporal
      dementia].
AB  - Disinhibition is the loss of psychological and physiological inhibition that
      leads to cognitive and motor impulsivity. The notion of impulsiveness is often
      linked to the function of the prefrontal cortex, and is usually understood as a
      lack of response inhibition. In other words, the subject is unable to suppress or
      withhold a previously rewarding response and the behavior appears impulsive. This
      has a social impact as disinhibition often affects the human social behavior. The
      "human social behavior" is how a person behaves properly with other people in a
      social environment. Frontotemporal Dementia produces changes in patients'
      behavior that frequently, manifest as disinhibition. Patients' social cognition
      is impaired and this is one of the key points for early diagnosis. All of these
      concepts will be review for a better understanding of Frontotemporal Dementia,
      and therefore, being able to differentiate it from other psychogeriatric
      disorders.

PMID- 21188309
TI  - [Emil :Kraepelin: the consolidation of mental diseases].

PMID- 21188310
TI  - [100 years of psychiatry].

PMID- 21188311
TI  - [Conflict and deficit in etiopathogenia].
AB  - Currently, there is a proliferation of theories and theoretical languages in the
      field of Mental Health. These different languages, with their accompanying
      discourse, can be a great source of confusion for the therapist, who is often
      forced to use them in clinical practice. The purpose of this paper is to describe
      and compare two principal theories in an attempt to integrate their different
      theoretical languages and approaches. To this end, two approaches in
      etiopathogenia, conflict and deficit, characteristic of two principal models,
      namely the medical-psychiatric model and the psychoanalytic-psychodynamic model,
      are described and compared. Firstly, deficit and psychic conflict are defined in
      the context of psychopathology. Secondly, Freud's complemental series is
      described and suggested as a model to enable the inclusion of both concepts in
      the etiopathology of mental disease. Thirdly, the diagnostic process is examined
      to illustrate how each model operates using a different methodology to collect
      data. In the field of psychiatry, clinical observation involves finding
      generalities to classify the disease in a nosography. In contrast, psychoanalysis
      investigates the conflict in the therapeutic relationship, and thus preserves the
      singularity of the subject. Finally, it is suggested that both models may be
      necessary and complementary, as they are both instrumental in the treatment of
      mental illness.

PMID- 21188312
TI  - [Cognitive intervention in mild cognitive impairment. A review].
AB  - Cognitive intervention involves training, stimulation and rehabilitation of
      higher brain functions, and stands as a non pharmacological treatment option for
      patients with cognitive symptoms and dementia. Mild Cognitive Impairment is a
      syndrome that appears to capture a group of individuals in a transitional state
      between normal aging and dementia. Patients with Mild Cognitive Impairment have a
      higher risk of progression to dementia. There are different subtypes of Mild
      Cognitive Impairment taking in consideration the cognitive domains that are
      affected, being the amnestic subtype the most common. This review examines the
      publications that explored the utility and efficacy of cognitive intervention in
      patients with Mild Cognitive Impairment. Although there is great variability in
      the studies design, in the type of intervention, in the treatment length and in
      the outcome measures selected, the majority of the papers reviewed reported a
      beneficial effect of the intervention, and none of them found an unfavorable
      result. Further adequately designed studies of cognitive treatment interventions
      in the different Mild Cognitive Impairment subtypes are needed to evaluate their
      potential benefits in ameliorating the patients' symptoms and in reducing the
      rate of progression to dementia.

PMID- 21188313
TI  - [Prenatal alcohol exposure as an etiological factor in neuropsychiatric diseases
      of childhood, adolescence and adulthood].
AB  - In Argentina, prenatal alcohol exposure (PAE) is an almost neglected condition as
      an important etiological factor for the induction of a wide spectrum of
      neuropsychiatric diseases that may appear during childhood, adolescence or
      adulthood. Children born to alcoholic mothers may show a spectrum of diseases
      ranging from an apparent normality to a profound mental retardation, passing
      through epilepsy, attention deficit disorders with or without hyperactivity,
      autism and pervasive developmental disorders, and different types of learning
      disorders. When adolescents, they may develop different kinds of personality
      disorders and substance abuse disorders. Finally, in adulthood, they may suffer
      from different types of affective and psychotic disorders, among others. A great
      number of those children may not develop their full mental and social
      potentiality as free individuals. They usually have diverse types of cognitive,
      attentional, mnemonic and affective impairments. Not infrequently, they engage in
      antisocial behaviors, have school or work troubles. In this work, I review the
      present clinical classifications of the disorders emerging from a PAE and the
      several neuropsychiatric diseases that can be induced by them, in order to call
      attention to the Argentinian neuropsychiatric community about the increasingly,
      although underdiagnosed, frequency of these disorders in our country.

PMID- 21188314
TI  - [Diogenes' syndrome: organic new disease or generated by the modern society?].
AB  - Diogenes syndrome is characterized by self neglect, domestic squalor and social
      withdrawal, abnormal collecting pattern and not preoccupation because of this way
      of life. The syndrome depends upon the personality disorder and social or medical
      problems. The diagnostic and treatment are multidisciplinary.

PMID- 21188315
TI  - [Bipolar disorder in the elderly].
AB  - Bipolar disorder is a frequent disorder in the elderly, with a prevalence of 0.1
      a 0.4%; a 10% of bipolar patients have mania onset after 50 years old. It has in
      ageing a more heterogeneous clinical presentation. The manic episodes are less
      severe, mixed depression is common, as well as confusion and cognitive
      impairment. A first manic episode in ageing can be secondary to medical illness.
      Treatment for bipolar disorder in ageing is similar to treatment for young
      patients. The differences are due to pharmacocinetic changes because of the age,
      with the comorbidity and with the etiology, if it is a secondary mania. Lithium
      can be the first choice for treating mania in patients with antecedent of good
      response and have tolerance to adverse effects, but because of its toxicity and
      secondary effects other possibilities may be considered: divalproate,
      cabamazepine, antipsychotics. There are some little studies that show lamotrigine
      efficacy in bipolar depression in elderly. We need more specific studies about
      bipolar disorder treatment in aging.

PMID- 21188316
TI  - [A multidisciplinary program for the treatment and follow up of depression in
      ambulatory elderly].
AB  - Depression is a common disorder in the elderly population; with significant
      elevated rates in terms of morbidity and mortality. Nonetheless it continues to
      be a subdiagnosticated disease with poor outcomes due to lack in the
      effectiveness of follow up. We developed collaborative intervention programs for
      elderly people in primary care at Hospital Italiano de Buenos Aires designing a
      randomized controlled trial in the ambulatory setting. Patients were recruited
      for an initial comprehensive geriatric evaluation, and then randomly assigned to
      the program intervention (n=18) or usual care (n=19). At 6 months, 55.5% of
      intervention patients had a 50% or greater reduction in depressive symptoms from
      baseline compared with 31.5% of those on usual care. Although the reduction of
      the outcomes of depressive symptoms is not statistically significative, these are
      preliminary data. We believe there is a trend toward better results with regard
      to improvements in depressive symptoms in patients in the intervention group, and
      that this will achieve statistical significance as the number of subjects
      recruited is increased in the course of the trial.

PMID- 21188317
TI  - [Pain: a psychogeriatric perspective].
AB  - Identifying pain in old people is very important, because it modifies daily life
      and functional performance, and it increases dependence from others. It may be
      expressed not only as a sensitive experience but also as psychological disorders.
      It interferes with cognitive area and it is a risk factor for suicide. The
      subject is considered from a multidimensional approach: in the diagnosis of pain
      in the interview and as a psychiatric evaluation in other medical areas.

PMID- 21188318
TI  - [The aging from the narrative identity].
AB  - This article is a theoretical study which aims to articulate the notion of
      narrative identity in the process of aging. This theory makes it possible to
      present the modalities of figuration of the subject, its broken meanings or
      refigurations and their elaborated narratives or configurations. The identity
      narrative explores the mechanisms by which a person develops stories using
      temporal references, relatives to past and future, and meaningful contexts, to
      acquire meanings in situations or life stages of disruption and disagreement on
      whether figuration.

PMID- 21188319
TI  - [Suicide in the elderly: analysis of "The Humbling" by Philip Roth].
AB  - In this paper we analyze the book "The Humbling" of Philip Roth in order to
      examine some of the keys that characterize the suicide in the elderly:
      narcissism, isolation, chronic pain, depression and hopelessness.

PMID- 21188320
TI  - [Madness in children near the end of the 19th century in Buenos Aires: doctoral
      thesis by Leonidas Carreno].

PMID- 21188321
TI  - [Study on madness in children (fragments). Thesis presented to obtain the title
      of Medical Doctor at the Medical School of the University of Buenos Aires in
      1888].

PMID- 21188322
TI  - Further insights into the causes of thrombocytopenia in chronic hepatitis C.

PMID- 21188323
TI  - Gastric anisakiasis: do not forget the clinical history!

PMID- 21188324
TI  - Hepatic portal venous gas.

PMID- 21188325
TI  - NAT2 polymorphisms and sporadic colorectal cancer survival.
AB  - BACKGROUND AND AIM: NAT2 gene polymorphisms can influence colorectal cancer (CRC)
      risk. We aimed to determine the extent to which NAT2 gene polymorphisms influence
      the survival of patients with sporadic colorectal cancer. METHODS: Seventy
      patients with sporadic colorectal cancer that underwent surgery at the 3rd
      Surgical Department of Cluj-Napoca between October 2003-May 2005 were randomly
      selected. Correlations between NAT2*5C(T341C), NAT2*5A(C481T), NAT2*6B(G590A),
      NAT2*7B(G857A) polymorphisms and survival of patients with different Dukes-MAC
      stages of CRC were analyzed. We compared patients with a slow acetylator genotype
      with those having an intermediate or rapid acetylator genotype. RESULTS: The slow
      acetylator 341CC genotype is a negative prognostic factor, 20% vs. 30.8%, as
      compared to rapid acetylator 341TT/TC genotypes (p=0.02) in the patients
      diagnosed with stage C CRC. For the same stage patients, the slow acetylator
      481CC was a positive prognostic factor, 33% vs. 25% (p=0.03). The slow acetylator
      590AA was a negative prognostic factor for the survival of patients with stages B
      and C, 0% vs. 31% (p=0.02). The slow acetylator 857AA genotype was a negative
      prognostic factor for the patients in stage B, survival rate 0.69% vs. 50%, and
      positive for patients with stage C, survival rate 50% vs. 21% (p=0.0101). The
      rapid acetylator 341TT/TC represented a good prognostic factor, while the slow
      341CC a negative one for stage D patients (p= 0.04, survival of 18.9%) HR=0.30
      with 95%, CI[0.025- 0.9810]. CONCLUSION: The NAT2 gene may be considered as a
      prognostic factor for the survival of patients with CRC.

PMID- 21188326
TI  - Risk factors predictive of poor quality preparation during average risk
      colonoscopy screening: the importance of health literacy.
AB  - BACKGROUND: Inadequate colonoscopy bowel preparation can lead to increased
      procedural time, decreased diagnostic yield, and an increased complication rate.
      Little is known about which patient characteristics may predict poor bowel
      preparation for routine, average-risk colonoscopy evaluation. METHODS: 300
      consecutive patients who underwent routine, average risk outpatient screening
      colonoscopy during 01/01/2005 to 12/30/2008 at a primary care internal medicine
      clinic were retrospectively identified. Patients were between 50-80 years old and
      used the standard preparation of 2000ml polyethylene glycol solution
      (MoviPrep)(R). Differences in mean values between each group (inadequate vs.
      adequate preparation) were compared using the Student t-test. Categorical
      variables were compared using chi2 test. A multivariate logistical regression
      analysis was performed to identify characteristics predictive of poor colonoscopy
      preparation. RESULTS: Of the 300 consecutive patients referred for routine
      outpatient colonoscopy examination, 15% had inadequate or poor colonoscopy
      preparation. The majority of patients with poor colonoscopy preparation (86.7%)
      reported either failure to complete the 2000 ml preparation or failure to follow
      written instructions. In the multivariate model, the four biggest clinical
      contributors to poor colonoscopy were an interpreter requirement, Medicaid
      insurance, single status, and having more than 8 active prescription medications.
      CONCLUSIONS: Among patients who underwent average-risk screening colonoscopy
      evaluation, the use of an interpreter and having Medicaid insurance were the
      largest predictors of inadequate colonoscopy preparation. These characteristics
      may be surrogate markers of lower health care literacy. Interventions to reduce
      poor colonoscopy preparation should be targeted at these patient populations.

PMID- 21188327
TI  - The prevalence and risk factors of hepatitis C virus infection in adult
      population in Romania: a nationwide survey 2006 - 2008.
AB  - AIMS: This study was aimed at determining the seroprevalence of hepatitis C virus
      (HCV) infection in Romania and the possible risk factors and modality of HCV
      transmission. METHODS: A nationwide cross-sectional survey among the adult
      population was conducted between 2006-2008 in Romania through a population
      multicenter stratified random cluster sampling. Serum samples from 13,460
      subjects were tested with a 3rd generation ELISA and a standardized questionnaire
      concerning the socio-demographic characteristics and potential risk factors was
      used. RESULTS: The prevalence rate of HCV infection in Romanian adult population
      was 3.23% with significant differences between the main geographical regions
      (Moldavia 4.25%, Wallachia & Dobrogea 3.35% and Transylvania & Banat 2.63%), as
      well as between different counties (maximum 7.19%, minimum 0.56%). Overall
      participation rate to the survey of the selected subjects was 74.69%. Risk
      factors for HCV infection were: blood/blood products transfusions (p=0.0001),
      previous surgery (elective and emergency, p=0.0001 and p=0.043, respectively),
      frequent hospitalizations (p=0.0001), injections at home (p=0.0001),
      accidents/trauma (p=0.0001), occupational hazard related to blood exposure
      (p=0.025), intravenous drug administration (p=0.002), a partner chronically
      infected with HCV/hepatitis B virus (HBV) (p=0.046), first sexual intercourse <18
      years (p=0.019), familial exposure to HCV/HBV infection (p=0.001) or to chronic
      HBV/HCV liver disease (p=0.001), personal history of chronic HBV infection
      (p=0.001). HCV RNA positivity was detected in 91% of the anti HCV positive
      subjects. CONCLUSIONS: Overall HCV prevalence in Romania is 3.23%. Both
      nosocomial and non-nosocomial routes are implicated as risk factors for HCV
      infection.

PMID- 21188328
TI  - Thrombocytopenia in chronic hepatitis C.
AB  - BACKGROUND AND AIMS: Thrombocytopenia in patients with chronic hepatitis C may be
      the result of several factors: bone marrow inhibition, the decrease of liver
      thrombopoietin production and an autoimmune mechanism. Clinical variables such as
      age, gender, severity of liver disease and degree of viremia could influence the
      severity of platelet reduction. The goal of this study is to determine the
      prevalent mechanism of thrombocytopenia in patients with chronic hepatitis C and
      the clinical predictors of its severity. METHODS: Eighty-one patients with
      chronic hepatitis C and thrombocytopenia were included. The viral inhibition on
      the bone marrow (central mechanism) was studied by performing bone marrow biopsy
      from the iliac crest. The presence of antiplatelet antibodies by ELISA assessed
      the peripheral mechanism. The clinical predictors included in the analysis were:
      age, gender, ALT level, liver fibrosis stage and HCV RNA. RESULTS: Coexistence of
      a central and peripheral mechanism was found in the vast majority (93.3%) of
      patients with severe thrombocytopenia (< 100,000/microL) and in most patients
      (61.53%) with moderate thrombocytopenia (100,000- 125,000/microL). In patients
      with less severe thrombocytopenia (126,000-149,000/microL), autoimmune
      destruction was the sole mechanism (85%). Thrombocytopenia was significantly
      associated with ALT values, viral load and stage of fibrosis. CONCLUSIONS: Our
      data demonstrates that chronic hepatitis C is associated with a variable degree
      of thrombocytopenia. As the disease advances, the platelet count decreases and,
      in most cases, both mechanisms are involved. The stage of fibrosis is one of the
      major determinants of thrombocytopenia.

PMID- 21188329
TI  - Nitric oxide levels and sustained virological response to pegylated-interferon
      alpha2a plus ribavirin in chronic HCV genotype 4 hepatitis: A prospective study.
AB  - BACKGROUND: The role of nitric oxide (NO) in infectious diseases is gaining
      attention because of its antiviral effects. AIM: To evaluate whether serum and
      hepatic NO levels are predictors of the outcome of treatment in patients with
      chronic hepatitis C genotype 4. METHODS: Fifty six patients with chronic HCV
      genotype 4 treated with pegylated interferon (IFN) alpha-2a plus ribavirin
      underwent blood tests, assessment of serum level of NO and hepatic tissue
      expression of NO synthase (iNOS) before and during treatment. RESULTS: The pre
      treatment serum NO level was significantly higher in sustained responders (SR)
      [39.583 (35-43.8)] compared to relapsers [36.25 (26-43.8)], and non responders
      (NR) [35.417 (25.0-43.8)]. During treatment, the serum NO level was significantly
      higher in SR [58.125 (47.9-60.6)] compared to relapsers [53.854 (47.9-59.4)] and
      NR [50 (42.9-59.4)]. The pre-treatment iNOS expression was significantly higher
      in SR [37.5 (15-75)] compared with either relapsers [25 (15-45)] and or NR [20 (2
      45)]. In multivariate logistic regression analysis, the serum NO was correlated
      with the virological response to pegylated interferon alpha-2a plus ribavirin
      therapy. CONCLUSION: In patients with chronic hepatitis C, nitric oxide levels
      may be associated with the outcome of pegylated-IFN-alpha 2a plus ribavirin
      treatment.

PMID- 21188330
TI  - How useful is contrast enhanced ultrasonography for the characterization of focal
      liver lesions?
AB  - AIM: Focal liver lesions (FLLs) are quite frequently discovered in daily practice
      at routine ultrasound. The aim of our study is to present a single centre
      experience concerning the use of contrast enhanced ultrasound (CEUS) in the
      characterization of FLL and to find when one can avoid using other expensive
      imaging modalities such as contrast enhanced CT or MRI. METHOD: We performed a
      prospective, single centre study during September 2009 - April 2010, and we
      evaluated 379 FLLs. A CEUS examination was considered conclusive if the FLL had a
      typical enhancement pattern according to the EFSUMB guidelines. RESULTS: From the
      379 cases with FLL, 198 (52.2%) were patients without known liver disease and 181
      (47.8%) with known chronic liver disease (156 had cirrhosis, 25 chronic
      hepatitis); in 296/379 cases (78.1%) CEUS was conclusive. CEUS allowed the
      positive diagnosis of benign vs. malignant lesion in 261/294 (88.8%) de novo FLLs
      (CEUS performed for the first time), while in 33 (11.2%) cases it was
      inconclusive and could not differentiate between benign or malignant lesions. The
      CEUS results included 129 (49.4%) benign lesions and 132 (50.6%) malignant.
      CONCLUSION: CEUS was conclusive in approximately 80% of the FLLs and the benign
      or malignant character of a lesion was demonstrated in about 90% of cases. Thus,
      when faced with an uncharacteristic FLL on standard ultrasound examination, our
      local strategy is to perform CEUS as a first-line investigation, thus avoiding
      other expensive examinations.

PMID- 21188331
TI  - Prognostic parameters and risk stratification in intensive care patients with
      severe liver diseases.
AB  - BACKGROUND AND AIM: Acute or chronic liver failure is associated with numerous
      complications and patients may require intensive care treatment, which is
      complex, time-consuming and often highly resource-intensive. Thus, it is
      necessary to identify clinical parameters that allow quick risk stratification.
      METHODS: In 117 patients with acute or chronic liver failure requiring ICU
      admission, the clinical parameters, risk scores and results of microbiological
      examinations were documented and correlated with the outcome (survivor vs. non
      survivor). RESULTS: Predictors of outcome were: Child-Pugh-Score (p < 0.01), MELD
      Score (p < 0.01), SAPS-II-Score (p < 0.05), bilirubin (p < 0.01), Glasgow Coma
      Scale (GCS) (p < 0.02), urine output (p < 0.01), requirement of catecholamine
      administration (p <0.004), serum creatinine (p < 0.01). The strongest predictors
      of outcome were in a multivariate model GCS (p = 0.006) and MELD-score (p =
      0.001). CONCLUSIONS: Risk stratification in our patient collective was feasible.
      Apart from parameters to assess kidney function and circulation, various scoring
      systems that had previously not been evaluated for this kind of patient
      collective seem to be the main predictors of outcome.

PMID- 21188332
TI  - Prevalence of cholelithiasis in patients subjected to liver transplantation for
      cirrhosis.
AB  - BACKGROUND AND AIMS: The prevalence of cholelithiasis in patients subjected to
      liver transplantation has not been evaluated yet. This study examines the
      prevalence of cholelithiasis in patients subjected to liver transplantation due
      to cirrhosis compared to an age- and sex-matched control group. METHODS: The
      electronic study protocols of 400 consecutive cirrhotic patients aged between 20
      and 69 years who had undergone liver transplantation for cirrhosis were evaluated
      to determine the presence of gallstones. RESULTS: The overall prevalence of
      cholelithiasis was higher in transplant recipients (96 patients; 24%) than in
      controls (38 patients; 9.5%) (p<0.001). There was no increase in the prevalence
      of cholelithiasis with age in the transplant recipients (p=0.332). Conversely,
      the prevalence of cholelithiasis increased with age in the control group
      (p<0.001). There was no difference in the gallstone prevalence between sexes in
      the transplant recipient group (p=0.102). However, the gallstone prevalence was
      2.2 times higher in females (14.8%) than in males (6.8%) in the control group
      (p=0.009). CONCLUSION: Prevalence of cholelithiasis is higher in patients
      subjected to liver transplantation for cirrhosis. In contrast with the general
      population, the prevalence of cholelithiasis in cirrhotic patients is similar in
      both sexes and does not increase with age.

PMID- 21188333
TI  - Worldwide H. pylori antibiotic resistance: a systematic review.
AB  - BACKGROUND AND AIMS: Prevalence of H. pylori antibiotic resistance is increasing
      worldwide, and it is the main factor affecting efficacy of current therapeutic
      regimens. Our aim was to review recent data on H. pylori resistance towards
      antibiotics in different countries. METHODS: A systematic review of studies
      concerning primary H. pylori antibiotic resistance published through January 2006
      to December 2009 was performed. Data were analyzed according to geographic area,
      age, sex, and gastroduodenal pathology. RESULTS: The overall H. pylori antibiotic
      resistance rates were 17.2% (95% CI: 16.5-17.9%) for clarithromycin, 26.7% (95%
      CI: 25.2-28.1%) for metronidazole, 11.2% (95% CI: 9.6-12.7%) for amoxycillin,
      16.2% (95% CI: 14.4-18%) for levofloxacin, 5.9% (95% CI: 4.7-7.1%) for
      tetracycline, 1.4% (95% CI: 0.81-9%) for rifabutin and 9.6% (95% CI: 8.5-10.7%)
      for multiple antibiotics. Prevalence rate of clarithromycin, metronidazole, and
      levofloxacin resistance significantly increased from Europe to Asia, America and
      Africa. Tetracycline resistance is low (<3%) in all countries, but Africa
      (43.9%). Prevalence of clarithromycin resistance was higher in non-ulcer
      dyspepsia patients, whilst metronidazole resistance was higher in peptic ulcer
      patients. Both resistances were significantly higher in female than in male
      patients. Data regarding amoxicillin resistance are highly conflicting.
      CONCLUSION: The worldwide H. pylori antibiotic resistance towards different
      antibiotics has increased. Such a phenomenon may affect therapeutic management in
      different countries.

PMID- 21188334
TI  - An overview of nonalcoholic steatohepatitis: past, present and future directions.
AB  - Nonalcoholic steatohepatitis (NASH) emerged from an anecdotal disease first
      described in 1981 to the most common cause of incident chronic liver disease at
      the end of the current decade. This article describes, from a historical
      perspective, some of the landmark changes in our perception and understanding of
      this disease. Natural history studies have shown the potential for serious liver
      damage and ultimately increased overall and liver-related mortality. The
      recognition of insulin resitance as an almost universal underlying condition in
      patients with NASH, its role as a major determinant of steatogenesis and possibly
      liver disease progression contributed to the identification of a probable cause
      for this disease, one that is amenable to therapeutic intervention. Consequently,
      screening for liver injury in patients with metabolic risk factors entered
      clinical practice in hepatology and endocrine diseases. NASH can coexist with
      other frequent liver diseases and often aggravate the course of liver injury;
      therefore it should be seen as an independent disease and not as an entity
      diagnosed only by exclusion of other hepatopathies. Finally, steatosis can have
      systemic consequences as it worsens insulin resistance, predicts the emergence of
      metabolic complications and increases the risk for cardiovascular events.
      Priorities for future research are the optimisation of non-invasive screening
      strategies, the identification of patients at risk of liver disease progression,
      the understanding of the hepatic carcinogenic potential and testing innovative
      pharmacological targets for therapy.

PMID- 21188335
TI  - Review of abdominal damage control and open abdomens: focus on gastrointestinal
      complications.
AB  - Massive trauma and abdominal catastrophes carry high morbidity and mortality. In
      addition to the primary pathologic process, a secondary systemic injury,
      characterized by inflammatory mediator release, contributes to subsequent
      cellular, end-organ, and systemic dysfunction. These processes, in conjunction
      with large-volume resuscitations and tissue hypoperfusion, lead to acidosis,
      coagulopathy, and hypothermia. This "lethal triad" synergistically contributes to
      further physiologic derangements and, if uncorrected, may result in patient
      death. One manifestation of the associated clinical syndrome is the development
      of intra-abdominal hypertension (IAH) and the abdominal compartment syndrome
      (ACS). The development of ACS is insidious. If not recognized and treated
      promptly, ACS leads to multi-system organ failure (MSOF) and mortality. Improved
      understanding of IAH and ACS led to the development of damage control (DC)/open
      abdomen (OA) as surgical decompressive strategy. The DC/OA approach consists of
      three basic management steps. During the initial step the abdomen is opened,
      hemorrhage/abdominal contamination are controlled, and temporary abdominal
      closure is performed (Stage I). The patient then enters Stage II - physiologic
      restoration with core rewarming, correction of coagulopathy and completion of
      acute resuscitation. After physiologic normalization, definitive management of
      injuries and eventual abdominal closure (Stage III) are achieved. The authors
      will provide an overview of the DC/OA approach, as well as the clinical diagnosis
      of ACS, followed by a discussion of DC/OA-associated complications, with focus on
      digestive system-specific complaints.

PMID- 21188338
TI  - Contrast-enhanced ultrasonography (CEUS) for the evaluation of the inflammation
      of the digestive tract wall.
AB  - The evaluation of digestive wall lesions has benefited in latter years from
      advanced, noninvasive techniques such as contrast enhanced ultrasound (CEUS).
      This method appreciates the microcirculation in inflamed bowel segments in terms
      of qualitative and quantitative parameters. Based on precise and reproducible
      criteria it evaluates the extension and the activity of disease, as well as the
      presence of complications. Monitoring studies using quantitative measurements of
      inflammation could lead to the development of prognostic factors regarding the
      treatment efficacy. The performance of this method can be improved by the use of
      intraluminal contrast media.

PMID- 21188339
TI  - Hemorrhagic colitis as a presenting feature of Wegener granulomatosis.
AB  - Wegener granulomatosis (WG) is an idiopathic small vessel vasculitis involving
      primarily airway and kidneys. Intestinal involvement of WG is rare and usually
      occurs after several years of WG and its treatment. We report a case of WG,
      presented initially as rapid-onset hemorrhagic pancolitis without any preexisting
      or concurrent illness or any medication use. A 79-year-old previously healthy
      woman presented with 2-day duration of bloody diarrhea. Colonoscopy showed
      pancolitis with numerous ulcers; the biopsy showed foci of inflammation,
      ulceration and hemorrhage in the lamina propria, without features of chronic
      inflammatory bowel disease. Her stool studies were negative for infection. She
      subsequently developed pulmonary hemorrhage and kidney dysfunction. Kidney biopsy
      showed pauci-immune necrotizing glomerulonephritis. She responded to a
      combination therapy of steroids, cyclophosphamide and plasmapheresis with
      resolution of intestinal and pulmonary symptoms and improvement of kidney
      function. This case represents the first known example of colitis as an initial
      presentation of WG without confounding etiologic factors. Hemorrhagic colitis,
      although uncommon, may be the major presenting feature of WG.

PMID- 21188340
TI  - Portal cavernoma in a patient with Crohn's disease associated with factor V
      Leiden mutation and antiphospholipid syndrome.
AB  - Portal vein thrombosis followed by the occurrence of a portal cavernoma is a rare
      condition that requires convergence between systemic predisposition and local
      factors in order to develop. Among the complications of inflammatory bowel
      diseases, such eventuality is quite unusual. Ulcerative colitis accounts for the
      majority of these vascular complications, while in Crohn's disease the occurrence
      of such events is exceptional. We present the case of a young male patient aged
      42, without any particular history, in whom the diagnosis of the first flare of
      colonic Crohn's disease was accompanied by the discovery of a portal cavernoma,
      followed by the demonstration of a heterozygous mutation factor V Leiden
      associated with the presence of an antiphospholipid syndrome with IgG
      anticardiolipin antibodies. This unusual association of portal vein thrombosis
      with antiphospholipid syndrome in Crohn's disease, observed according to our
      knowledge only in one other instance, raises the discussion regarding the
      convergent action of general thrombophilic (hereditary and acquired) and local
      factors in the genesis of vascular complications of inflammatory bowel diseases.

PMID- 21188341
TI  - Prolonged survival after the surgical management of a solitary malignant melanoma
      lesion within the pancreas: A case report of curative resection.
AB  - Solitary involvement of the pancreas in patients with malignant melanoma is rare
      and the role of surgery in these patients is not defined. We present a patient
      with prolonged survival following aggressive surgical management for a solitary
      metastatic lesion within the pancreas. A 69-year-old male presented with a 10-day
      history of painless jaundice. His past medical history included a wide local
      excision for a superficial spreading melanoma, and subsequent loco-regional
      recurrence requiring lymph node dissection. Imaging on presentation showed a
      solitary mass in the head of the pancreas, with no signs of metastases. The
      patient underwent a pancreato-duodenectomy. Histology reported a metastatic
      malignant melanoma with clear excision margins. There was no nodal involvement
      and he remained disease-free eight years later. The survival of patients seems to
      be affected by the ability to perform a curative resection, and by a long disease
      free interval between the treatment of the initial lesion and disease recurrence.
      Curative surgical resection should be offered to selected patients with a
      solitary pancreatic malignant melanoma metastasis. Such aggressive management may
      lead to prolonged, and disease-free survival.

PMID- 21188342
TI  - Diffuse form of Caroli's disease: therapeutical approach in a female patient with
      recurrent cholangitis.
AB  - A 49-year old female was admitted to the 3rd Surgical Clinic Cluj with clinical
      signs of cholangitis. She had had these symptoms for 30 years and in 2007 she was
      diagnosed as suffering from a diffuse form of Caroli's disease. On admission, a
      biological syndrome of cholestasis was noticed, associated with an inflammatory
      syndrome and hepatocytolysis. The imaging examinations confirmed the presence of
      bilateral intrahepatic cysts communicating with the biliary tree and intrahepatic
      lithiasis. Surgery was performed with left lobectomy, cholecystectomy, lavage of
      the right biliary tree and single loop cholangio-jejunal Roux-en-Y anastomosis.
      The patient had a favorable postoperative evolution and was discharged on the 7th
      day. The optimal therapeutic solution for this patient would have been a liver
      transplantation. However, given the emergency presentation, the surgery choice
      was to treat the present complications, namely the structural damage in the left
      lobe, the microabcesses at this level, the intrahepatic lithiasis and
      cholangitis. Caroli's disease, due to its complications, may impose to the
      surgeon to choose between different therapeutical strategies before liver
      transplantation.

PMID- 21188343
TI  - Percutaneous ethanol injection in the treatment of hepatocellular carcinoma in
      cirrhosis: a simple, effective and cheap procedure for percutaneous ablation.

PMID- 21188344
TI  - Impact of duration of hemodialysis on gastrointestinal symptoms in patients with
      end stage renal failure.

PMID- 21188345
TI  - Failure in wound healing following percutaneous gastrostomy insertion in patients
      on corticosteroids.

PMID- 21188346
TI  - Autonomic dysfunction and risk of cholelithiasis in cirrhosis.

PMID- 21188347
TI  - Sexually transmitted infection as a cause of proctitis: asking about sexual
      orientation is more useful in the diagnosis than endoscopy or histology.

PMID- 21188348
TI  - Incidental diagnosis of stromal tumor of the stomach by percutaneous ultrasound
      guided biopsy.

PMID- 21188349
TI  - Eliminating expression of erucic acid-encoding loci allows the identification of
      "hidden" QTL contributing to oil quality fractions and oil content in Brassica
      juncea (Indian mustard).
AB  - Oil content and oil quality fractions (viz., oleic, linoleic and linolenic acid)
      are strongly influenced by the erucic acid pathway in oilseed Brassicas. Low
      levels of erucic acid in seed oil increases oleic acid content to nutritionally
      desirable levels, but also increases the linoleic and linolenic acid fractions
      and reduces oil content in Indian mustard (Brassica juncea). Analysis of
      phenotypic variability for oil quality fractions among a high-erucic Indian
      variety (Varuna), a low-erucic east-European variety (Heera) and a zero-erucic
      Indian variety (ZE-Varuna) developed by backcross breeding in this study
      indicated that lower levels of linoleic and linolenic acid in Varuna are due to
      substrate limitation caused by an active erucic acid pathway and not due to
      weaker alleles or enzyme limitation. To identify compensatory loci that could be
      used to increase oil content and maintain desirable levels of oil quality
      fractions under zero-erucic conditions, we performed Quantitative Trait Loci
      (QTL) mapping for the above traits on two independent F1 doubled haploid (F1DH)
      mapping populations developed from a cross between Varuna and Heera. One of the
      populations comprised plants segregating for erucic acid content (SE) and was
      used earlier for construction of a linkage map and QTL mapping of several yield
      influencing traits in B. juncea. The second population consisted of zero-erucic
      acid individuals (ZE) for which, an Amplified Fragment Length Polymorphism (AFLP)
      based framework linkage map was constructed in the present study. By QTL mapping
      for oil quality fractions and oil content in the ZE population, we detected novel
      loci contributing to the above traits. These loci did not co-localize with mapped
      locations of the fatty acid desaturase 2 (FAD2), fatty acid desaturase 3 (FAD3)
      or fatty acid elongase (FAE) genes unlike those of the SE population wherein
      major QTL were found to coincide with mapped locations of the FAE genes. Some of
      the new loci identified in the ZE population could be detected as 'weak'
      contributors (with LOD < 2.5) in the SE population in which their contribution to
      the traits was "masked" due to pleiotropic effects of erucic acid genes. The
      novel loci identified in this study could now be used to improve oil quality
      parameters and oil content in B. juncea under zero-erucic conditions.

PMID- 21188350
TI  - Using a limited mapping strategy to identify major QTLs for resistance to
      grapevine powdery mildew (Erysiphe necator) and their use in marker-assisted
      breeding.
AB  - A limited genetic mapping strategy based on simple sequence repeat (SSR) marker
      data was used with five grape populations segregating for powdery mildew
      (Erysiphe necator) resistance in an effort to develop genetic markers from
      multiple sources and enable the pyramiding of resistance loci. Three populations
      derived their resistance from Muscadinia rotundifolia 'Magnolia'. The first
      population (06708) had 97 progeny and was screened with 137 SSR markers from
      seven chromosomes (4, 7, 9, 12, 13, 15, and 18) that have been reported to be
      associated with powdery or downy mildew resistance. A genetic map was constructed
      using the pseudo-testcross strategy and QTL analysis was carried out. Only
      markers from chromosome 13 and 18 were mapped in the second (04327) and third
      (06712) populations, which had 47 and 80 progeny, respectively. Significant QTLs
      for powdery mildew resistance with overlapping genomic regions were identified
      for different tissue types (leaf, stem, rachis, and berry) on chromosome 18,
      which distinguishes the resistance in 'Magnolia' from that present in other
      accessions of M. rotundifolia and controlled by the Run1 gene on chromosome 12.
      The 'Magnolia' resistance locus was termed as Run2.1. Powdery mildew resistance
      was also mapped in a fourth population (08391), which had 255 progeny and
      resistance from M. rotundifolia 'Trayshed'. A locus accounting for 50% of the
      phenotypic variation mapped to chromosome 18 and was named Run2.2. This locus
      overlapped the region found in the 'Magnolia'-based populations, but the allele
      sizes of the flanking markers were different. 'Trayshed' and 'Magnolia' shared at
      least one allele for 68% of the tested markers, but alleles of the other 32% of
      the markers were not shared indicating that the two M. rotundifolia selections
      were very different. The last population, 08306 with 42 progeny, derived its
      resistance from a selection Vitis romanetii C166-043. Genetic mapping discovered
      a major powdery mildew resistance locus termed Ren4 on chromosome 18, which
      explained 70% of the phenotypic variation in the same region of chromosome 18
      found in the two M. rotundifolia resistant accessions. The mapping results
      indicate that powdery mildew resistance genes from different backgrounds reside
      on chromosome 18, and that genetic markers can be used as a powerful tool to
      pyramid these loci and other powdery mildew resistance loci into a single line.

PMID- 21188352
TI  - HbA(1c) levels in schoolchildren with type 1 diabetes are seasonally variable and
      dependent on weather conditions.
AB  - AIMS/HYPOTHESIS: We evaluated seasonal HbA(1c) changes in children with type 1
      diabetes and its relation with measures of weather conditions. METHODS: HbA(1c)
      changes over more than 3 years were evaluated in type 1 diabetic patients who
      were younger than 18 years and had diabetes duration of more than 12 months, and
      correlated with measures of weather conditions (ambient temperature, hours of
      sunshine and solar irradiance). After comparison of autocorrelation patterns,
      patterns of metabolic control and meteorological data were evaluated using
      Spearman rank correlation. RESULTS: A total of 3,935 HbA(1c) measurements in 589
      school (>= 7 years) and 88 preschool (<7 years) children were analysed. Mean (+/-
      SD) HbA(1c) level for the whole study period was 7.65 +/- 1.12%. The lowest
      HbA(1c) levels were observed in late summer and the highest in winter months,
      with differences consistently exceeding 0.44%. Autocorrelation analysis of
      HbA(1c) levels in schoolchildren showed a sine-wave pattern with a cycle length
      of roughly 12 months, which mirrored changes in ambient temperature. Strong
      negative correlations of HbA(1c) with ambient temperature (R = -0.56; p =
      0.0002), hours of sunshine (R= -0.52; p = 0.0007) and solar irradiance (R = 
      0.52; p = 0.0006) were present in schoolchildren, but not in preschoolers (p >=
      0.29 for each correlation). CONCLUSIONS/INTERPRETATION: Seasonal changes of
      HbA(1c) levels in schoolchildren with type 1 diabetes are a significant
      phenomenon and should be considered in patient education and diabetes management.
      They may potentially affect the results of clinical trials using HbA(1c) levels
      as their primary outcome, as well as HbA(1c)-based diagnosis of diabetes.

PMID- 21188353
TI  - Replication of genome-wide association studies (GWAS) loci for fasting plasma
      glucose in African-Americans.
AB  - AIMS/HYPOTHESIS: Chronically elevated blood glucose (hyperglycaemia) is the
      primary indicator of type 2 diabetes, which has a prevalence that varies
      considerably by ethnicity in the USA, with African-Americans disproportionately
      affected. Genome-wide association studies (GWASs) have significantly enhanced our
      understanding of the genetic basis of diabetes and related traits, including
      fasting plasma glucose (FPG). However, the majority of GWASs have been conducted
      in populations of European ancestry. Thus, it is important to conduct replication
      analyses in populations with non-European ancestry to identify shared loci
      associated with FPG across populations. METHODS: We used data collected from non
      diabetic unrelated African-American individuals (n = 927) who participated in the
      Howard University Family Study to attempt to replicate previously published GWASs
      of FPG. Of the 29 single nucleotide polymorphisms (SNPs) previously reported, we
      directly tested 20 in this study. In addition to the direct test, we queried a
      500 kb window centred on all 29 reported SNPs for local replication of additional
      markers in linkage disequilibrium (LD). RESULTS: Using direct SNP and LD-based
      comparisons, we replicated multiple SNPs previously associated with FPG and
      strongly associated with type 2 diabetes in populations with European ancestry.
      The replicated SNPs included those in or near TCF7L2, SLC30A8, G6PC2, MTNR1B,
      DGKB-TMEM195 and GCKR. We also replicated additional variants in LD with the
      reported SNPs in ZMAT4 and adjacent to IRS1. CONCLUSIONS/INTERPRETATION: We
      identified multiple GWAS variants for FPG in our cohort of African-Americans.
      Using an LD-based strategy we also identified SNPs not previously reported,
      demonstrating the utility of using diverse populations for replication analysis.

PMID- 21188354
TI  - The effect of nicotine and trauma context on acoustic startle in smokers with and
      without posttraumatic stress disorder.
AB  - RATIONALE: Exaggerated startle response is a prominent feature of posttraumatic
      stress disorder (PTSD) although results examining differences in the acoustic
      startle response (ASR) between those with and without PTSD are mixed. One
      variable that may affect ASR among persons with PTSD is smoking. Individuals with
      PTSD are more likely to smoke and have greater difficulty quitting smoking. While
      smokers with PTSD report that smoking provides significant relief of negative
      affect and PTSD symptoms, the effects of smoking or nicotine deprivation on
      startle reactivity among smokers with PTSD are unknown. OBJECTIVES: The purposes
      of the current study were to (1) examine baseline acoustic startle response (ASR)
      in smokers with and without PTSD under conditions of overnight abstinence, (2)
      evaluate the effect of smoking on ASR, and (3) evaluate the contextual effects of
      trauma versus neutral script presentations. METHODS: ASR was measured among 48
      smokers with and without PTSD in the context of a 2 (group: PTSD vs. non-PTSD) x
      2 (context: trauma vs. neutral) x 3 (smoking condition: usual brand cigarette vs.
      denicotinized cigarette vs. no smoking) design. RESULTS: Effects of modest size
      indicated that (1) PTSD participants demonstrated higher ASR (2) compared to non
      PTSD participants, PTSD participants reported greater negative affect following a
      trauma-related script, and (3) following a trauma-related script and smoking a
      usual brand cigarette, PTSD participants demonstrated higher ASR. CONCLUSIONS:
      Although many smokers with PTSD report that smoking reduces PTSD symptoms,
      results suggest that smoking may actually potentiate or maintain an exaggerated
      startle response.

PMID- 21188355
TI  - Visual information interacts with neuromuscular factors in the coordination of
      bimanual isometric force.
AB  - The role of perceptual-motor processes in the coordination and control of
      movement is a long standing issue. Nevertheless, there is no coherence on
      theoretical perspectives with their being frameworks that emphasize perceptual,
      motor and perceptual-motor processes in coordination and control. The purpose of
      this study was to examine the interactive effects of visual information and
      factors of neuromuscular organization (force level, force direction, and
      homologous muscle pairs) on coordination patterns in bimanual isometric force
      production. In Experiment 1, the participants were required to abduct two index
      fingers isometrically and produce simultaneous forces such that their sum matched
      the constant force target specified at two force levels (10 and 40% of maximum
      voluntary contraction (MVC)). Visual information of the force outputs was either
      present or absent between conditions. The results showed that the coordination
      patterns interact with visual feedback in that the two finger forces exhibit
      negative correlation with vision and positive correlation without vision, with
      stronger correlation in each case found at higher force levels. In Experiment 2,
      the force direction and muscles involved in the task were different between the
      hands. In comparison with Experiment 1, the negative correlation was stronger
      with vision at 40% MVC (but equal at 10% MVC), and positive correlation was
      weaker without vision at 10% MVC (but equal at 40% MVC). The findings provide
      further evidence that the coordination patterns in bimanual isometric force
      production are specified by the interaction of task-relevant visual information
      and force level and, to a lesser degree by force direction and the muscles
      involved in the task. The capacity to exploit information mediates coordination
      and control, and the effective utilization of information is dependent on the
      specific action.

PMID- 21188358
TI  - The influences of time-of-day and sleep deprivation on postural control.
AB  - The aim of this study was to check the combined and/or dissociated influences of
      time-of-day and sleep deprivation on postural control. Twenty subjects
      participated in test sessions which took place at 6:00 am, 10:00 am, 2:00 pm and
      6:00 pm either after a normal night's sleep or after a night of total sleep
      deprivation. Postural control was evaluated by COP surface area, LFS ratio and
      Romberg's index. The results showed that postural control fluctuates diurnally
      according to three different periods, pronounced by sleep deprivation: (1) at
      6:00 am, there was no modification by sleep deprivation; (2) at 10:00 am and 2:00
      pm, an interaction effect was observed for COP surface area and LFS ratio after
      sleep deprivation. Values of COP surface area were significantly higher (P <
      0.01) following the night of sleep deprivation than after the normal night's
      sleep (139.36 +/- 63.82 mm2 vs. 221.72 +/- 137.13 mm2 and 143.78 +/- 75.31 mm2
      vs. 228.65 +/- 125.09 mm2, respectively); (3) at 6:00 pm, the LFS ratio was
      higher than during the two other periods (P < 0.001) whereas COP surface area
      decreased to the level observed at 6:00 am. At this time-of-day, only the LFS
      ratio was significantly increased (P < 0.05) by the night of sleep deprivation
      (0.89 +/- 0.14 vs. 1.03 +/- 0.30). This temporal evolution in postural control
      does not seem to be related to any deterioration in visual input as Romberg's
      index (150.09 +/- 97.91) was not modified, regardless of the test session.

PMID- 21188359
TI  - Activity of human motor system during action observation is modulated by object
      presence.
AB  - Neurons in the monkey mirror neuron system (MNS) become active when actions are
      observed or executed. Increases in activity are greater when objects are engaged
      than when the actions are mimed. This modulation occurs even when object
      manipulation is hidden from view. We examined whether human motor systems are
      similarly modulated during action observation because such observation-related
      modulations are potentially mediated by a putative human MNS. Transcranial
      magnetic stimulation (TMS) was used to elicit motor-evoked potentials (MEPs) of a
      grasping muscle while participants observed actual or pantomimed grasping
      movements whose endpoints were sometimes hidden from view. MEP amplitudes were
      found to be modulated by object presence. Critically, the object-based modulation
      was found when the participant directly observed object manipulation and when the
      object manipulation had to be inferred because it was hidden. These findings
      parallel studies of MNS activity in monkeys and support the hypothesis that the
      MNS influences motor system activity during action observation. Although the
      object-based modulation of MEP amplitudes was consistent with the hypotheses, the
      direction of the modulation was not--MEP amplitudes decreased during action
      observation in contrast to the increase that has previously been observed. We
      suggest that the decrease in MEP amplitude on object-present trials resulted from
      inhibitory mechanisms that were activated to suppress the observation-evoked
      response codes from generating overt muscle activity.

PMID- 21188360
TI  - Where do we look when we walk on stairs? Gaze behaviour on stairs, transitions,
      and handrails.
AB  - Stair walking is a challenging locomotor task, and visual information about the
      steps is considered critical to safely walk up and down. Despite the importance
      of such visual inputs, there remains relatively little information on where gaze
      is directed during stair walking. The present study investigated the role of
      vision during stair walking with a specific focus on gaze behaviour relative to
      (1) detection of transition steps between ground level and stairs, (2) detection
      of handrails, and (3) the first attempt to climb an unfamiliar set of stairs.
      Healthy young adults (n = 11) walked up and down a set of stairs with 7 steps
      (transitions were defined as the two top and bottom steps). Gaze behaviour was
      recorded using an eye tracker. Although participants spent most part of the time
      looking at the steps, gaze fixations on stair features covered less than 20% of
      the stair walking time. There was no difference in the overall number of
      fixations and fixation time directed towards transitions compared to the middle
      steps of the stairs. However, as participants approached and walked on the
      stairs, gaze was within 4 steps ahead of their location. The handrail was rarely
      the target of gaze fixation. It is noteworthy that these observations were
      similar even in the very first attempt to walk on the stairs. These results
      revealed the specific role of gaze behaviour in guiding immediate action and that
      stair transitions did not demand increased gaze behaviour in comparison with
      middle steps. These findings may also indicate that individuals may rely on a
      spatial representation built from previous experience and/or visual information
      other than gaze fixations (e.g. dynamic gaze sampling, peripheral visual field)
      to extract information from the surrounding environment.

PMID- 21188361
TI  - The effect of feature saliency on haptic subitizing.
AB  - 'Subitizing' refers to fast and error-free numerosity judgment for small (<4)
      sets of items. For larger sets, the slower process of 'counting' is used.
      Counting has a serial character, whereas subitizing is believed to have a
      parallel character. While subitizing was initially found in vision, it has been
      shown to exist in touch as well. In vision, it has been demonstrated that adding
      distractor items to a set of target items influences numerosity judgment of the
      target items. Subitizing was in this case only possible if the distractor item is
      highly salient among the targets. In the present study, we investigated the
      effect of adding a distractor item on haptic judgement of a set of target items.
      To this end, we asked subjects to judge the number of spheres grasped in their
      hand. Either a cube or an ellipsoid could be added to the set. A cube among
      spheres has been shown to be highly salient, while an ellipsoid among spheres is
      not. Our results show that adding a distractor item led to an increase in the
      response time slopes regardless of the distractor shape. Subitizing was, however,
      only possible in the case of a salient distractor. This is in agreement with
      results from vision.

PMID- 21188362
TI  - Evidence for a dissociation between the control of oculomotor capture and
      disengagement.
AB  - The current study investigated whether capture of the eyes by a salient onset
      distractor and the disengagement of the eyes from that distractor are driven by
      the same or by different underlying control modes. A variant of the classic
      oculomotor capture task was used. Observers had to make a saccade to the only
      gray circle among red background circles. On some trials, a green (novel color),
      red (placeholder color) or gray (target color) distractor square was presented
      with sudden onset. Results showed that when participants reacted fast, oculomotor
      capture was primarily driven by bottom-up pop-out: both types of distractors
      (green and gray) that popped out among the red background elements showed more
      capture than a red distractor that did not pop-out. In contrast to initial
      capture, disengagement of the eyes from the distractor was driven by top-down
      target-distractor similarity effects. We also examined the time-course of this
      effect. The distractor could change from green to either the target or
      placeholder color. When the color change was early in time (30-40 ms after its
      onset), dwell times were strongly affected by the change, whereas the effect on
      oculomotor capture was weak. Importantly, a change occurring as early as 60-80 ms
      after distractor onset did neither affect capture nor dwell times, corroborating
      the assumption of parallel programming of saccades.

PMID- 21188364
TI  - Multistage audiovisual integration of speech: dissociating identification and
      detection.
AB  - Speech perception integrates auditory and visual information. This is evidenced
      by the McGurk illusion where seeing the talking face influences the auditory
      phonetic percept and by the audiovisual detection advantage where seeing the
      talking face influences the detectability of the acoustic speech signal. Here, we
      show that identification of phonetic content and detection can be dissociated as
      speech-specific and non-specific audiovisual integration effects. To this end, we
      employed synthetically modified stimuli, sine wave speech (SWS), which is an
      impoverished speech signal that only observers informed of its speech-like nature
      recognize as speech. While the McGurk illusion only occurred for informed
      observers, the audiovisual detection advantage occurred for naive observers as
      well. This finding supports a multistage account of audiovisual integration of
      speech in which the many attributes of the audiovisual speech signal are
      integrated by separate integration processes.

PMID- 21188363
TI  - Representation of virtual arm movements in precuneus.
AB  - Arm movements can easily be adapted to different biomechanical constraints.
      However, the cortical representation of the processing of visual input and its
      transformation into motor commands remains poorly understood. In a visuo-motor
      dissociation paradigm, subjects were presented with a 3-D computer-graphical
      representation of a human arm, presenting movements of the subjects' right arm
      either as right or left arm. In order to isolate possible effects of coordinate
      transformations, coordinate mirroring at the body midline was implemented
      independently. In each of the resulting four conditions, 10 normal, right-handed
      subjects performed three runs of circular movements, while being scanned with
      O(15)-Butanol-PET. Kinematic analysis included orientation and accuracy of a
      fitted ellipsoid trajectory. Imaging analysis was performed with SPM 99 with
      activations threshold at P < 0.0001 (not corrected). The shape of the trajectory
      was dependent on the laterality of the arm, irrespective of movement mirroring,
      and accompanied by a robust activation difference in the contralateral precuneus.
      Movement mirroring decreased movement accuracy, which was related to increased
      activation in the left insula. Those two movement conditions that cannot be
      observed in reality were related to an activation focus at the left middle
      temporal gyrus, but showed no influence on movement kinematics. These findings
      demonstrate the prominent role of the precuneus for mediating visuo-motor
      transformations and have implications for the use of mirror therapy and virtual
      reality techniques, especially avatars, such as Nintendo Wii in
      neurorehabilitation.

PMID- 21188365
TI  - Initial experiences with the Amplatzer Vascular Plug 4 for permanent occlusion of
      the internal carotid artery in the skull base in patients with head and neck
      tumors.
AB  - INTRODUCTION: As the first report in the literature, we present our initial
      experiences with the latest generation's Amplatzer Vascular Plug 4 (AVP4) as a
      device for permanent occlusion of the internal carotid artery in its course in
      the skull base. METHODS: Permanent occlusion of the internal carotid artery in
      the skull base was performed in four patients after administration of an
      intravenous heparin bolus (three patients preoperatively to facilitate radical
      surgery of head and neck tumors, one patient with a palliative intent to reduce
      tumor arrosion bleeding risk). RESULTS: In all patients, the deployment of the
      AVP4 in the artery's course in the skull base was feasible. In two patients,
      placement was possible in the cavernous segment of the internal carotid artery,
      and in the other two patients, more proximal in the artery's foramen lacerum and
      petrous segment, respectively. Occlusion was accomplished in one patient with one
      AVP4 (occlusion time 25 min), in two patients with two AVP4 (occlusion time 20
      min in each case), and in one patient with one AVP4, three additional fibered
      coils and two Gelfoam pledgets (occlusion time more than 2 h). Complications did
      not occur in any of the four patients. CONCLUSION: The AVP4 may be a promising
      device for permanent occlusion of the internal carotid artery, allowing in its
      latest generation, navigability as distal as the cavernous segment in some, but
      not in all cases. Difficulties may still occur in very tortuous vessel anatomy.

PMID- 21188366
TI  - Isolation and characterization of the CYP2D6 gene in Felidae with comparison to
      other mammals.
AB  - The highly polymorphic CYP2D6 protein metabolizes about 25% of commonly used
      drugs and underlies a broad spectrum of drug responses among individuals. In
      contrast to extensive knowledge on the human CYP2D6 gene, little is known about
      the gene in non-human mammals. CYP2D6 mRNA from 23 cats (Felidae) spanning seven
      species were compared to available CYPD6 sequences in ten additional mammals and
      multiple allelic variants in humans. A relatively high mean dN/dS ratio (0.565)
      was observed, especially within Felidae. Pairwise dN/dS ratios were non
      monotonically distributed with respect to evolutionary distance suggesting either
      positive selection or retention of slightly deleterious mutations. Positive
      selection on specific codons, most notably in regions involved in substrate
      recognition and membrane anchoring is supported and the possible influence of
      diet on specific amino acid changes in substrate binding sites is discussed.

PMID- 21188367
TI  - Fetal demise secondary to massive rhabdomyoma in the early second trimester of
      pregnancy.
AB  - Rhabdomyoma is the most common cardiac tumor in fetuses, often associated with
      tuberous sclerosis complex and usually diagnosed in the third trimester of
      pregnancy, with a benign course in the majority of cases. The hemodynamic impact
      of cardiac tumor depends on the location and size of the mass and the presence of
      dysrhythmia (4). Fetal cardiac rhabdomyoma accounts for less than 10% of fetal
      demise cases (1). This report presents a case of massive cardiac rhabdomyoma
      filling the entire right heart with pericardial extension, leading to hydrops and
      subsequent fetal death in the early second trimester of pregnancy.

PMID- 21188368
TI  - Subclavian pseudoaneurysm repair after Blalock-Taussig shunt placement.
AB  - A 7-day-old male with tricuspid atresia, pulmonary atresia, and D-transposition
      of the great vessels underwent surgical placement of a modified Blalock-Taussig
      (mBT) shunt and was found to have a pseudoaneurysm on the follow-up
      echocardiogram. Surgical exploration identified a pseudoaneurysm arising from the
      right subclavian artery and not from the innominate artery at the site of the mBT
      shunt. It was concluded that this was caused by an inadvertent needlestick during
      central line placement. The fistula tract between the right subclavian artery and
      the false aneurysm was oversewn, and the postoperative course was unremarkable.

PMID- 21188369
TI  - Complete atrioventricular canal with guarded primum septal defect.
AB  - Common atrioventricular canal (CAVC) is a common congenital heart lesion
      resulting from a defect in development of the endocardial cushions during early
      embryogenesis. Depending on the type of defect, CAVC can encompass a spectrum of
      lesions ranging from partial atrioventricular (AV) canal to complete AV canal. We
      describe a case of CAVC with unique anatomy in a 4-month-old male infant with
      Down syndrome.

PMID- 21188370
TI  - Left-ventricular noncompaction in a pediatric population: predictors of survival.
AB  - Left-ventricular noncompaction (LVNC) is an echocardiographic finding of
      increasing frequency in pediatrics; however, predictors of outcomes have been
      difficult to identify. We conducted a retrospective review of pediatric patients
      at the Morgan Stanley Children's Hospital of New York from January of 1993 to
      September of 2009 to identify predictors of the primary outcome of death or heart
      transplantation. LVNC was identified in 50 patients, 34 of them < 1 year of age.
      Death or transplantation occurred in 26 patients, with a median survival of 1.17
      years after presentation. Patients surviving 1 year after presentation had 75%
      conditional survival, and patients surviving 2 years after presentation had 92%
      conditional survival. Hemodynamic instability, poor ventricular function, and LV
      dilatation were each independent predictors of poor outcome. Of the 21 patients
      who presented with hemodynamic instability, 17 died or underwent transplantation
      at a median of 0.08 years after presentation. In conclusion, LVNC is recognized
      more in younger patients; however, age is not a predictor of outcome. Patients
      who present with hemodynamic instability and poor ventricular function have
      decreased transplant-free survival, and most poor outcomes occur within the first
      year after presentation. Therefore, early listing for transplant may lead to
      better outcomes in this population.

PMID- 21188371
TI  - Comparison of gastrointestinal morbidity after Norwood and hybrid palliation for
      complex heart defects.
AB  - This study aimed to compare the incidence of gastrointestinal complications among
      infants with single-ventricle heart defects after three first-stage palliation
      strategies: Norwood-modified Blalock-Taussig shunt (mBTS), Norwood right
      ventricle-to-pulmonary artery conduit (Sano), and hybrid procedures. A
      retrospective chart review was performed in a pediatric cardiac intensive care
      unit at a tertiary care medical center. The subjects were 32 neonates who had
      undergone single-ventricle palliation including 13 Norwood-mBTS, 11 Sano, and 8
      hybrid procedures. The measurements included baseline as well as pre- and
      postoperative patient characteristics. The primary outcome was postoperative
      intraabdominal complications, and the secondary outcomes were feeding intolerance
      and necrotizing enterocolitis (NEC). Intraabdominal complications occurred for
      34%, feeding intolerance for 13%, and NEC for 13% of the patients. The hybrid
      patients had a higher incidence of intraabdominal complications (75%) than the
      Norwood-mBTS (31%) or Sano (9%) patients (P = 0.01). The relative risk for
      intraabdominal complications in the hybrid group was 3.6 (95% confidence interval
      [CI], 1.5-8.7). In the multivariate analysis, the hybrid procedure remained an
      independent predictor of intraabdominal complications (hazard ratio, 8.4; 95% CI,
      2.0-34.5). The hybrid, Norwood-mBTS, and Sano patients did not differ
      significantly in terms of feeding intolerance (25, 15, and 0%, respectively; P =
      0.25) or NEC (25, 8, and 9%; P = 0.46). Gastrointestinal morbidity was common
      regardless of the palliative approach, although the hybrid patients had the
      highest incidence of intraabdominal complications. This supports the need for
      caution in using enteral nutrition with all single-ventricle patients, including
      the hybrid population. Patients undergoing the hybrid procedure may benefit from
      implementation of standardized feeding protocols.

PMID- 21188372
TI  - Comparison of posterolateral thoracotomy and video-assisted thoracoscopic
      clipping for the treatment of patent ductus arteriosus in neonates and infants.
AB  - This study was designed to compare the long-term clinical outcomes and costs
      between video-assisted thoracic surgery (VATS) and posterolateral thoracotomy
      (PT) in neonates and infants. This study enrolled 302 patients with isolated
      patent ductus arteriosus (PDA) from January 2002 to 2007 and followed them up
      until April 2010. A total of 134 patients underwent total VATS (VATS group), and
      168 underwent PDA closure through PT (PT group). The two groups were compared
      according to clinical outcomes and costs. The demographics and preoperative
      clinical characteristics of the patients were similar in the two groups. No
      cardiac deaths occurred, and the closure rate was 100% successful in both groups.
      The operating, recovery, and pleural fluid drainage times were significantly
      shorter in the VATS group than in the PT group. Statistically significant
      differences in length of incision, postoperative temperature, and acute procedure
      related complications were observed between the two groups. The cost was $1,150.3
      +/- $221.2 for the VATS group and $2415.8 +/- $345.2 for the PT group (P < 0.05).
      No cardiac deaths or newly occurring arrhythmias were detected in either group
      during the follow-up period. Statistically significant differences in the rate of
      residual shunt and scoliosis were observed between the two groups. The left
      ventricular end-diastolic diameter and the pulmonary artery diameter could be
      restored to normal in the VATS group but not in the PT group. The study confirmed
      that VATS offers a minimally traumatic, safe, and effective technique for PDA
      interruption in neonates and infants.

PMID- 21188373
TI  - Prenatal diagnosis of a patient with tetralogy of Fallot and an absent pulmonary
      valve.

PMID- 21188374
TI  - Underrecognition of elevated blood pressure readings in children after early
      repair of coarctation of the aorta.
AB  - Hypertension after repair of coarctation of the aorta (CoA) is the outcome
      variable most closely associated with adverse long-term events such as stroke and
      myocardial infarction. This study sought to evaluate the outpatient management of
      casual blood pressure (BP) measurements in young children after early repair of
      CoA. A retrospective analysis was performed of clinical findings,
      echocardiographic data, casual BP recordings, and subsequent BP management of 114
      children with CoA repair aged 1-13 years during 338 outpatient visits managed at
      two congenital cardiac centers. Children with associated significant congenital
      heart disease or corrective surgery after the age of 6 months were excluded from
      the study. Blood pressure was documented at 233 clinic visits (69%), and systolic
      BP (SBP) was above 95th percentile for age and sex in 45 instances (19%). This
      represented an elevated SBP recording for 31 children (27%), with two or more
      successive elevated recordings for 11 children (10%). Of 12 subjects receiving
      antihypertensive medication, three had inadequate BP control. Blood pressure is
      not documented at approximately 30% of outpatient visits of children with
      repaired CoA. When elevated BP is documented, in all cases no recorded action was
      taken. This may have significant implications for cardiovascular outcomes in this
      cohort of patients.

PMID- 21188375
TI  - Novel NKX2-5 mutations in patients with familial atrial septal defects.
AB  - Atrial septal defect (ASD) is a common cardiovascular malformation and an
      important contributor to substantial morbidity and mortality. Increasing evidence
      demonstrates that mutated NKX2-5, a gene encoding a homeobox transcription factor
      crucial to cardiogenesis, is a significant genetic determinant for congenital
      ASD. Nevertheless, the genetic basis for ASD in a majority of ASD patients
      remains largely unknown. In the current study, the entire coding region of NKX2-5
      was sequenced initially for 58 unrelated probands with familial ASD. The
      relatives of the probands harboring identified mutations and 200 unrelated
      control individuals were subsequently genotyped. Three novel heterozygous NKX2-5
      mutations (p.P43GfsX59, p.C46 W, and p.S179F) were identified respectively in
      three families with autosomal dominantly inherited ASD. These mutations, absent
      in 200 control individuals, cosegregated with ASD in the families that had
      complete penetrance. The findings expand the spectrum of mutations in NKX2-5
      linked to ASD and contribute to genetic counseling, clinical interventions, and
      prenatal prevention of ASD for individuals with genetic susceptibility.

PMID- 21188376
TI  - Hypolithic cyanobacteria supported mainly by fog in the coastal range of the
      Atacama Desert.
AB  - The Atacama Desert is one of the driest places on Earth, with an arid core highly
      adverse to the development of hypolithic cyanobacteria. Previous work has shown
      that when rain levels fall below ~1 mm per year, colonization of suitable quartz
      stones falls to virtually zero. Here, we report that along the coast in these
      arid regions, complex associations of cyanobacteria, archaea, and heterotrophic
      bacteria inhabit the undersides of translucent quartz stones. Colonization rates
      in these areas, which receive virtually no rain but mainly fog, are significantly
      higher than those reported inland in the hyperarid zone at the same latitude.
      Here, hypolithic colonization rates can be up to 80%, with all quartz rocks over
      20 g being colonized. This finding strongly suggests that hypolithic microbial
      communities thriving in the seaward face of the Coastal Range can survive with
      fog as the main regular source of moisture. A model is advanced where the
      development of the hypolithic communities under quartz stones relies on a
      positive feedback between fog availability and the higher thermal conductivity of
      the quartz rocks, which results in lower daytime temperatures at the quartz-soil
      interface microenvironment.

PMID- 21188377
TI  - Interactions between testate amoebae and saprotrophic microfungi in a Scots pine
      litter microcosm.
AB  - In all terrestrial ecosystems, testate amoebae (TA) encounter fungi. There are
      strong indications that both groups engage in multiple interactions, including
      mycophagy and decomposition of TA shells, processes which might be fundamental in
      nutrient cycling in certain ecosystems. Here, we present the results of an
      experiment focusing on interactions between TA and saprotrophic microfungi
      colonizing Scots pine (Pinus sylvestris L.) litter needles. The needles were
      collected from a temperate pine forest and cultivated in damp chambers. Over a
      few weeks, melanized mycelium of Anavirga laxa Sutton started to grow out of some
      needles; simultaneously, the common forest-soil TA Phryganella acropodia (Hertwig
      and Lesser) Hopkinson reproduced and spread around the mycelium. We investigated
      whether a potential relationship between TA and saprotrophic microfungi exists by
      comparing the composition of TA communities on and around the needles and testing
      the spatial relationship between the A. laxa mycelium and P. acropodia shells in
      the experimental microcosm. Additionally, we asked whether P. acropodia utilized
      the A. laxa mycelium as a nutrient source and screened whether P. acropodia
      shells were colonized by the microfungi inhabiting the experimental microcosm.
      Our results indicate that saprotrophic microfungi may affect the composition of
      TA communities and their mycelium may affect distribution of TA individuals in
      pine litter. Our observations suggest that P. acropodia did not graze directly on
      A. laxa mycelium, but rather fed on its exudates or bacteria associated with the
      exudates. The fungus Pochonia bulbillosa (Gams & Malla) Zare & Gams was often
      found parasitising encysted shells or decomposing already dead individuals of P.
      acropodia. TA and pine litter microfungi engage in various direct and indirect
      interactions which are still poorly understood and deserve further investigation.
      Their elucidation will improve our knowledge on fundamental processes influencing
      coexistence of soil microflora and microfauna.

PMID- 21188378
TI  - Quantitative analysis of Hb Bart's in cord blood by capillary electrophoresis
      system.
AB  - It has long been recognized that the presence of hemoglobin (Hb) Bart's in
      newborn's blood is associated with alpha-thalassemia. However, the automated high
      performance liquid chromatography or low-performance liquid chromatography system
      is unable to quantify the amount of Hbs Bart's and H, which are eluted at the
      retention time close to 0 min. This study used automatic capillary
      electrophoresis (CE) system to diagnose various types of alpha-thalassemia in 587
      cord blood samples, including 429 normal alpha-globin genotype, 120 cases of
      thalassemia with one alpha-globin gene defect, 34 cases with two alpha-globin
      genes defect, and four cases with three alpha-globin genes defect. The result
      showed that the level of Hb Bart's in cord blood was increased accordingly with
      the increasing numbers of the defective alpha-globin genes. In addition, Hb
      Bart's level at 0.2%, as measured by CE, can be used as a cut-off point for alpha
      thalassemia diagnosis in newborns.

PMID- 21188379
TI  - Pharmacokinetics, pharmacodynamics and metabolism of the dimeric
      pyrrolobenzodiazepine SJG-136 in rats.
AB  - PURPOSE: The dimeric pyrrolobenzodiazepine SJG-136 (NSC 694501, SG2000) has
      potent in vitro antiproliferative activity and in vivo antitumor activity
      associated with binding in the minor groove of DNA and formation of covalent
      interstrand DNA cross-links. The pharmacokinetics and in vitro metabolism of SJG
      136 and as well as the feasibility of using the Comet assay to measure in vivo
      interstrand DNA cross-links, was assessed in the rat. METHODS: SJG-136
      pharmacokinetics and pharmacodynamics were characterized in rats following single
      dose administration of 15 and 50 MUg/kg or multiple-dose administration of 25
      MUg/kg/day for 5 days. DNA damage was measured in peripheral blood mononuclear
      cells using the Comet assay. SJG-136 oxidative metabolism was characterized in
      rat liver microsomes. RESULTS: SJG-136 half-life, clearance and volume of
      distribution values were 9 min, 190 ml/min/m(2), and 1780 ml/m(2), respectively.
      SJG-136 did not accumulate in plasma during treatment with 25 MUg/kg/day for 5
      days. Treatment with SJG-136 produced the anticipated DNA interstrand cross
      links, as well as DNA strand breaks, in rat PBMCs. Oxidative metabolism of SJG
      136 in rat liver microsomes was catalyzed by CYP3A isoforms and produced a
      previously unreported monomeric metabolite. CONCLUSIONS: Plasma concentrations of
      SJG-136 associated with pharmacological activity and in vitro antiproliferative
      activity were achieved with doses that were tolerated by rats. CYP3A isoforms are
      the predominant P450s catalyzing SJG-136 metabolism. The comet assay detects DNA
      damage in PBMCs from rats treated with SJG-136 and is being used in clinical
      trials to monitor in vivo lesions produced by SJG-136.

PMID- 21188380
TI  - Preoperative radiotherapy with capecitabine and mitomycin C in locally advanced
      rectal carcinoma.
AB  - PURPOSE: To evaluate the efficacy and safety of preoperative radiotherapy with
      capecitabine and mitomycin C in patients with locally advanced rectal cancer.
      METHODS: A prospective, open-label, non-randomized, phase II study was performed
      on 49 patients with locally advanced rectal cancer. Preoperative radiotherapy was
      conducted on linear accelerators (15 or 18 MV) with a tumor dose of 45 Gy in 25
      fractions over 5 weeks, combined with mitomycin C 7 mg/m(2) on days 1 and 29 and
      oral capecitabine 825 mg/m(2) twice daily on days 1-35. Surgery was performed 5-6
      weeks after the end of chemoradiation. The primary study endpoint was
      histopathological complete regression rate (pCR; Dworak grade 4). RESULTS:
      Disease stage at diagnosis was T3 in 34 patients (69%) and T4 in 15 patients
      (31%). Positive lymph nodes were diagnosed in 28 patients (57%). Toxicity (all
      grades) was documented in 35 patients (71%). Grade 3 toxicities were radiation
      dermatitis (25%), diarrhea (2%), neutropenia (2%), and granulocytopenia (2%). No
      patient experienced grade 4 toxicity. A pCR was seen in 8 (16%, 95% CI 9-29%)
      patients, a major response was noted in 24 (49%) patients and a minor response in
      14 (29%) patients. R0 resection was performed in 46 patients (93.9%) and R1 in 3
      patients (6.1%). Histopathological tumor downstaging was documented in 26
      patients (53%). One-year disease-free survival was 93.3% and 1-year survival was
      97.7%. CONCLUSION: Preoperative chemoradiation with capecitabine and mitomycin C
      appeared to be effective with low toxicity in patients with locally advanced
      rectal cancer.

PMID- 21188381
TI  - Beta cell regeneration in human pancreas.
AB  - The issue of beta cell regeneration in human pancreas is probably one of the most
      controversial aspects of type 1 diabetes research. In this review, we will first
      describe the known mechanisms underlying beta cell development and expansion in
      normal human pancreatic development because it is likely that such mechanisms
      might also play a role in beta cell regeneration. The sensu strictiori definition
      of beta cells implies replacement of lost beta cell mass by new beta cells. In
      our discussion, however, we will use the term in a more general way, defining as
      regeneration the formation of new beta cells, whether or not a loss of beta cells
      has actually occurred. The potential mechanisms of beta cell regeneration in the
      human pancreas will be discussed in the second part of this review. In
      particular, we will analyze beta cell regeneration through proliferation of beta
      cells, neogenesis from non-beta cell precursors, and transdifferentiation from
      alpha cells. In the third part of this review, we will explore the arguments for
      and against the ability of the human pancreas to regenerate functional beta cells
      in the context of type 1 diabetes and in other pathological conditions.

PMID- 21188382
TI  - The effect of low-level laser to apoptosis of chondrocyte and caspases
      expression, including caspase-8 and caspase-3 in rabbit surgery-induced model of
      knee osteoarthritis.
AB  - The purpose of this study was to observe the effect of 810-nm low-level laser to
      apoptosis of chondrocyte and related proteins, including caspase-3 and caspase-8,
      in rabbit surgery-induced model of knee osteoarthritis. A total of 24 New Zealand
      White rabbits were randomly assigned into 3 groups: test group, model group, and
      normal group. The rabbits in test group and model group received anterior
      cruciate ligament transection in the right knee. Six weeks after transection, the
      rabbits in test group were given 10-session 810-nm laser illumination. Eight
      weeks after transection, all animal were killed. Modified Mankin Score was made
      for histological assessment. The caspases expressions and chondrocytes apoptosis
      were tested using the immunohistochemistry and TUNEL assessment, respectively.
      The modified Mankin Score of test group was significantly lower than model group
      (P < 0.01) and higher than normal group (P < 0.01). The caspase-8 expression of
      test group was lower than model group and higher than normal group, but no
      significant difference was found (P > 0.05). This study revealed that the 810-nm
      low-level laser can improve cartilage structure, prevent articular cartilage
      degradation and significantly decrease the expression of caspase-3 in this
      surgery-induced OA model. Further studies are needed.

PMID- 21188383
TI  - Gene identification in black cohosh (Actaea racemosa L.): expressed sequence tag
      profiling and genetic screening yields candidate genes for production of
      bioactive secondary metabolites.
AB  - Black cohosh (Actaea racemosa L., syn. Cimicifuga racemosa, Nutt., Ranunculaceae)
      is a popular herb used for relieving menopausal discomforts. A variety of
      secondary metabolites, including triterpenoids, phenolic dimers, and serotonin
      derivatives have been associated with its biological activity, but the genes and
      metabolic pathways as well as the tissue distribution of their production in this
      plant are unknown. A gene discovery effort was initiated in A. racemosa by
      partial sequencing of cDNA libraries constructed from young leaf, rhizome, and
      root tissues. In total, 2,066 expressed sequence tags (ESTs) were assembled into
      1,590 unique genes (unigenes). Most of the unigenes were predicted to encode
      primary metabolism genes, but about 70 were identified as putative secondary
      metabolism genes. Several of these candidates were analyzed further and full
      length cDNA and genomic sequences for a putative 2,3 oxidosqualene cyclase (CAS1)
      and two BAHD-type acyltransferases (ACT1 and HCT1) were obtained. Homology-based
      PCR screening for the central gene in plant serotonin biosynthesis, tryptophan
      decarboxylase (TDC), identified two TDC-related sequences in A. racemosa. CAS1,
      ACT1, and HCT1 were expressed in most plant tissues, whereas expression of TDC
      genes was detected only sporadically in immature flower heads and some very young
      leaf tissues. The cDNA libraries described and assorted genes identified provide
      initial insight into gene content and diversity in black cohosh, and provide
      tools and resources for detailed investigations of secondary metabolite genes and
      enzymes in this important medicinal plant.

PMID- 21188384
TI  - Oral immunogenicity of tomato-derived sDPT polypeptide containing Corynebacterium
      diphtheriae, Bordetella pertussis and Clostridium tetani exotoxin epitopes.
AB  - DPT vaccine, designed to immunize against diphtheria, pertussis, and tetanus, has
      been shown to be effective in humans. Nevertheless, dissatisfaction with the
      whole-cell preparations is due to the reactogenicity, which has to lead to the
      development of new safer formulations. Previously, we described the expression in
      tomato of a plant-optimized synthetic gene encoding the recombinant polypeptide
      sDPT, containing mainly immunoprotective epitopes of the diphtheria, pertussis
      and tetanus exotoxins and two adjuvants. In this study, we examined whether the
      ingestion of tomato-derived sDPT protein induces specific antibodies in mice
      after three weekly doses scheme. A positive group immunized with DPT toxoids was
      included. Specific antibody levels were assessed in serum, gut and lung. Sera
      tested for IgG antibody response to pertussis, tetanus and diphtheria toxin
      showed responses to the foreign antigens; interestingly, the response to
      diphtheria epitope was similar to those observed in the positive group. We found
      higher IgG1 than IgG2a responses in serum. A modest IgG response was observed in
      the tracheopulmonary fluid. High response of IgA against tetanus toxin was
      evident in gut, which was statistically comparable to that obtained in the
      positive group. The levels of response in these groups were higher than those in
      mice that received wild-type tomato. These findings support the concept of using
      transgenic tomatoes expressing sDPT polypeptide as model for edible vaccine
      against diphtheria, pertussis, and tetanus.

PMID- 21188385
TI  - Comparative effectiveness research in urology.
AB  - BACKGROUND: Comparative effectiveness research (CER) has come to remain at the
      forefront of political and scientific debates of health care. The aim of this
      article is to describe the attributes of CER and implications to the field of
      urology. METHODS: The authors reviewed the published urology literature and
      recent CER publications including the Institute of Medicine reports. RESULTS: CER
      is defined as the evaluation of the relative efficacy of diagnostic tests,
      treatments, and health care services against the current standards of care, with
      the goal of reducing health care costs while simultaneously improving quality.
      Significant government funds were recently devoted to CER efforts. The Institute
      of Medicine identified 25 of the most urgently needed areas for research of which
      three pertain to Urology: screening for prostate cancer, comparing effectiveness
      of treatments for localized prostate cancer, and use of imaging in diagnosing,
      staging, and monitoring cancer patients. Some of the important required
      strategies to formulate successful CER include involving health care stakeholders
      to aid in selecting appropriate topics, utilizing study populations that
      represent real life practice, and the development of large-scale national
      databases and registries. CONCLUSION: Several topics of urologic care have
      already been identified in the first quartile of CER priorities, and many others
      need to be added. Following the proposed research, designs for CER should be done
      while abiding by robust methodology, maintaining transparency, and effectively
      translating research into clinical practice.

PMID- 21188386
TI  - Technical difficulties of transumbilical laparoendoscopic single-site
      adrenalectomy: comparison with conventional laparoscopic adrenalectomy.
AB  - PURPOSE: Interest in laparoendoscopic single-site (LESS) surgery has increased in
      recent years. The aim of this study was to evaluate the feasibility and safety of
      transumbilical LESS adrenalectomy and to elucidate the technical differences
      between LESS and conventional laparoscopic surgery. METHODS: This study was
      comparing 10 consecutive transumbilical LESS adrenalectomies and 10 conventional
      laparoscopic adrenalectomies performed between March 2006 and April 2010 for
      benign adrenal tumors. Perioperative parameters were compared, and we reviewed
      our surgical videos and analyzed technical characteristics of the surgeries.
      RESULTS: There was no open conversion in laparoscopic group, no additional port
      placement in LESS group, and no perioperative complications in either group. No
      significant differences in operative time, estimated blood loss, or resumption of
      oral intake were observed between two groups. Pneumoperitoneum time did not
      differ between LESS and laparoscopic groups (91.2 vs. 74.3 min, P = 0.257). In
      LESS group only, time was needed for adjustment of roticulator (14.5 +/- 8.1
      min). After subtracting the time needed for adjustment, operative time between
      two groups was more comparable (76.7 vs. 74.3 min, P = 0.880). One-handed
      manipulation time in LESS group decreased in a time-dependent manner (r = -0.806,
      P < 0.0049). Tissue re-grasping during operation was more frequently observed in
      LESS group (16.2 vs. 2.2 times, P < 0.001). CONCLUSIONS: Transumbilical LESS
      adrenalectomy is feasible and comparable to conventional laparoscopic
      adrenalectomy. There are still obvious technical difficulties associated with
      LESS surgery, and it is essential that these be overcome in order to improve this
      surgical technique.

PMID- 21188387
TI  - Elevated B-type natriuretic peptide level as a marker of subsequent
      thromboembolic events in patients with atrial fibrillation.
AB  - The aim of the present study was to assess whether elevated B-type natriuretic
      peptide (BNP) levels, as an objective marker of heart failure, is a predictor of
      subsequent thromboembolic events in patients with atrial fibrillation (AF) during
      oral anticoagulant therapy. This was a post hoc analysis of a single-center,
      prospective, observational study. Consecutive patients with AF (261 patients, 74
      +/- 9 years old, 153 paroxysmal AF) treated with warfarin were included for the
      analysis. BNP level at baseline examination was measured to assess the
      relationship of this parameter with subsequent thromboembolic events. BNP levels
      at the time of entry were 161 +/- 188 (5-1,500, median 105) pg/ml. During an
      average follow-up time of 762 +/- 220 (median 742) days, nine (1.8%/year)
      thromboembolic events occurred. Receiver operating characteristic curve showed
      that an optimal cut-off value for BNP to predict thromboembolic events was 218
      pg/ml. There were six thromboembolic events observed among patients with a
      baseline BNP levels >=200 pg/ml (n = 73) as compared to three such events in
      those with baseline BNP levels <200 pg/ml (n = 188). Kaplan-Meier curves for BNP
      level showed that elevated BNP level (>=200 pg/ml) was significantly associated
      with thromboembolic events (p < 0.01). Cox-proportional hazard analysis also
      revealed that a high BNP level (>=200 pg/ml) was a significant predictor of
      subsequent thromboembolic events (hazard ratio 5.32, p = 0.018). Elevated BNP
      levels (>=200 pg/ml) could be a useful marker of subsequent thromboembolic events
      in patients with AF during oral anticoagulant therapy. However, the number of
      patients and events in this study was small and drawing a definite conclusion was
      not possible with this small sample size. Therefore, further larger-scale,
      multicenter studies are needed to confirm these findings.

PMID- 21188388
TI  - Neovascularization in a mouse model via stem cells derived from human fetal
      amniotic membranes.
AB  - In this study, we evaluated the effect of culture-expanded mesenchymal stem cells
      (MSCs), derived from amniotic membranes, on neovascularization and blood flow, in
      an animal model of limb ischemia in immune-deficient mice. MSCs were cultured
      from human amniotic membranes by collagenase digestion. Human amniotic
      mesenchymal stem cells (hAMSCs) were administered intramuscularly at three
      different sites of the ischemic leg whose femoral vessels were ligated. After 4
      weeks of culture, a population of homogeneous mesenchymal cells was isolated from
      the human amniotic membranes after confluence was reached. We performed three
      different groups of mice model [controls, hAMSCs, conditioned media from the
      hAMSCs (hAMSCs-CM)]. The blood flow recovery in the hindlimb ischemia model was
      significantly higher in the hAMSC-transplanted group than in the control group.
      Moreover, hAMSCs-CM significantly improved the cutaneous blood flow. The
      histological examination showed that red fluorescence (CM-DiI)-labeled hAMSCs was
      detected in the interstitial tissues between the muscle fibers 2 weeks after
      transplantation. The results of this study showed that hAMSCs may be an
      attractive, alternative source of progenitor or stem cells for basic research as
      well as clinical applications.

PMID- 21188389
TI  - Short-term effects of double-layer autologous vein graft on restraint of
      excessive distension and alleviation of neointimal hyperplasia in a porcine
      saphenous vein graft model.
AB  - Although the use of external vein graft support seems a promising approach to
      prevent neointimal hyperplasia and wall thickening in vein grafts, its extensive
      clinical application still has a long way to go. The aim of this study was to
      evaluate short-term effects of self-designed double-layer autologous saphenous
      vein graft on restraining excessive distension of vein graft and alleviating
      neointimal hyperplasia in a porcine model. Left and right hind femoral arteries
      of 24 white pigs were randomly divided into an experimental group (double-layer
      vein graft) and a control group (single-layer vein graft). After 1 h of
      implantation, then 1, 2, and 4 weeks later, the mean inner diameter of the vein
      grafts in the experimental group measured by Doppler-ultrasound was 2.7 +/- 0.1,
      2.8 +/- 0.1, 2.9 +/- 0.1, and 3.1 +/- 0.1 mm, respectively; mean peak blood flow
      velocity measured by Doppler-ultrasound was 96.7 +/- 12.8, 93.7 +/- 11.5, 89.4 +/
      9.6 and 84.6 +/- 10.1 cm/s, respectively, while the mean neointimal thicknesses
      were 47.1 +/- 7.7, 93.7 +/- 15.1, and 177.4 +/- 25.5 MUm at 1, 2 and 4 weeks,
      respectively. As compared to the control group, inner diameter and neointimal
      thickness of vein grafts in the experimental group were significantly lower,
      while mean peak blood flow velocity was significantly higher at 1, 2, and 4 weeks
      after implantation. The proliferation index in the experimental group was also
      significantly lower within 4 weeks after implantation. The self-designed double
      layer autologous saphenous vein graft restrains early excessive distension of
      vein graft and alleviates early neointimal hyperplasia.

PMID- 21188391
TI  - Multifocal colonic mucosa-associated lymphoid tissue lymphoma with synchronous
      tubular adenoma: a coincidental association?

PMID- 21188390
TI  - Predictive value of VEGF gene polymorphisms for metastatic colorectal cancer
      patients receiving first-line treatment including fluorouracil, irinotecan, and
      bevacizumab.
AB  - PURPOSE: The aim of this study is to evaluate the influence of germline vascular
      endothelial growth factor (VEGF) gene polymorphisms (VGPs) on the efficacy of the
      anti-VEGF antibody bevacizumab (Bev) in metastatic colorectal cancer (MCRC)
      patients. METHODS: Forty MCRC patients eligible for a first-line therapy were
      enrolled in this prospective trial and treated with
      FOLinate/Fluorouracil/Irinotecan (FOLFIRI) + Bev (male/female = 22:18, age
      (median) = 61 years). Eight VGPs within the promoter/5'UTR region were evaluated
      in patient blood samples. Primary endpoint was association between VGPs and
      median progression-free survival (mPFS). Overall radiological response rate
      (ORR), overall survival (OS), and toxicity were assessed as secondary outcomes.
      RESULTS: VGPs -2578, -1512, -1451, -1411, and -460 were in complete linkage
      disequilibrium and therefore analyzed as haplotype (two variants: Haplo1: A-18 bp
      insertion-T-4G-C and Haplo2: C-18 bp deletion-C-5G-T, respectively). Seventeen
      patients Haplo2/Haplo2 had significantly shorter mPFS compared to 23 patients
      Haplo1/Haplo1 or Haplo1/Haplo2 (mPFS, 9 vs. 15.4 months, respectively, p = 0.02;
      hazard ratio (HR), 2.64). Also, VGPs -152 (G/G vs. G/A + A/A) and -1154 (G/G vs.
      G/A + A/A) were significantly associated with PFS (mPFS, 8.9 vs. 15.4 months, p =
      0.007; HR, 3.53 and 9.8 vs. 16 months, p = 0.03, HR, 2.32, respectively). In the
      multivariate analysis including also biochemical variables known to influence
      prognosis, VGP -1154 retained an independent predictive value for mPFS (G/G over
      G/A + A/A = HR, 4.43; p = 0.02). With regard to ORR, only VGP -634 was
      significantly associated with response (G/G vs. G/C + C/C = 64% vs. 14%, p =
      0.03). No significant influence on OS and toxicity by the investigated VGPs was
      observed. CONCLUSIONS: Although these data need to be confirmed in larger trials,
      investigation of germline VGPs may help identify patients who are more sensitive
      to anti-VEGF agents.

PMID- 21188392
TI  - Unique abscess in ulcerative colitis.

PMID- 21188393
TI  - Extracorporeal perfusion of free muscle flaps in a porcine model using a
      miniaturized perfusion system.
AB  - INTRODUCTION: The development of techniques in transplantation medicine-
      including various aspects--has made extraordinary progress within the past three
      decades. However, the transplantation of free tissue flaps with the common
      problem of limited ischemia time frames remains an area in which the
      understanding of mechanism during ischemia and reperfusion is still limited.
      Thus, similar to other organ transplantations, the prolongation of ischemic time
      and the possibility to perform an ex vivo perfusion is desirable. The purpose of
      this study was to create a closed and steady ex vivo perfusion system in order to
      analyze the possibility of using a miniaturized perfusion system for free muscle
      flaps that could also be clinically used for other solid organ transplantation.
      MATERIALS AND METHODS: The rectus abdominis muscles of six german pigs were used
      in the study. Each of these free muscle flaps was perfused for a period of 2 h
      using a pulsatile and closed pump perfusion system by cannulating the arterial
      and venous vessels of the flap pedicle. During the ex vivo perfusion parameters
      such as arterial and venous pressures were measured continuously. RESULTS: A
      total of six ex vivo, closed and steady perfusions have been successfully
      performed. The optimal arterial flow rate of ex vivo perfusion of rectus
      abdominis muscle flaps was evaluated to be 10 ml/min. The constant measurement of
      arterial (46 +/- 13 mmHg) and venous (-1 +/- 1 mmHg) pressure in this ex vivo
      setting showed steady parameters during a period for up to 2 h. CONCLUSION: The
      data of this study indicate that the ex vivo perfusion of free muscle flaps is
      technically feasible and a closed and steady circulation is manageable for a
      period of up to 2 h.

PMID- 21188394
TI  - Arthroscopically assisted percutaneous osteosynthesis of displaced transverse
      patellar fractures with figure-eight wiring through paired cannulated screws.
AB  - INTRODUCTION: For treatment of displaced transverse patellar fractures, open
      reduction and internal fixation is the standard reconstructive method. The role
      of percutaneous osteosynthesis is still unclear and worth of further
      investigation. Our hypothesis is that satisfactory reduction and rigid fixation
      is possible for the treatment of displaced transverse patellar fractures with
      some percutaneous techniques. Here, we present and evaluate a minimally invasive
      technique for these patellar fractures. PATIENTS AND METHODS: This is a
      retrospective study. Twenty-one patients with 21 transverse patellar fractures
      were treated with our percutaneous technique in acute phase. The minimally
      invasive surgery was achieved by closed reduction and fixation with modified
      Carpenter's technique, using figure-eight wiring through two parallel cannulated
      screws under the assistance of arthroscopy and fluoroscopy. The patients were
      followed up to an average of 38.8 months (range 26-48). Main outcome measurements
      included radiographic assessment, range of motion, Lysholm scores, complications,
      and reoperations. RESULTS: Radiographically, all fractures healed at a mean of
      11.0 weeks (range 9-13). Mean total range of motion of knee joint was 140.1
      degrees  (range 127-152). Functional assessment of Lysholm scores was 93.9 points
      (range 86-100). Malreduction, loss of reduction, and infection were not observed
      in 21 patients. Complications were three cases (14%) of hardware irritation, and
      needed a second operation for removal. CONCLUSIONS: Under the control of
      arthroscopy and fluoroscopy, we successfully treated 21 displaced transverse
      patellar fractures by percutaneously osteosynthesis. This is a safe and
      reproducible method for transverse patellar fractures. However, it is not
      indicated for severely comminuted fractures.

PMID- 21188395
TI  - Locking plates have increased torsional stiffness compared to standard plates in
      a segmental defect model of clavicle fracture.
AB  - OBJECTIVE: To evaluate the effect of locked plate technology to resist torsion in
      a clavicle fracture model of segmental bone loss. METHODS: Forty-four synthetic
      clavicles were repaired with either 3.5 mm locked compression plate (LCP) or 3.5
      mm low-contact dynamic compression plate (LCDCP). They were divided into two
      groups of 22 specimens. Each group was tested to evaluate torsional stiffness,
      load at failure, deflection at failure, and unconstrained plate motion. RESULTS:
      LCP group showed significantly greater stiffness in torsion compared to the LCDCP
      group (p < 0.001). Average difference was 20.9%. Load at failure was not
      significantly different (p < 0.07). Deflection at failure was significantly less
      for the LCP group (p < 0.03). Unconstrained motion or plate 'looseness' was
      significantly less for the LCP group (p < 0.017). CONCLUSIONS: In a simulated
      model of segmental clavicle fracture, a LCP provided more stiffness and less
      deflection than a low-contact dynamic compression plate.

PMID- 21188396
TI  - Primary malignant clavicular tumours: a clinicopathological analysis of six cases
      and evaluation of surgical management.
AB  - Primary malignant tumours of the clavicle are extremely rare and little is known
      regarding their clinicopathological characteristics and outcomes of surgical
      management. The aim of the study is to analyse the clinical, imaging, and
      histological features of six patients with malignant tumours of the clavicle and
      present the outcome of cleidectomy in four of them. A review of the literature is
      also provided. Six cases were included in this series: two plasmocytomas; three
      PNETs, one non-Hodgkin lymphoma, one high-grade chondrosarcoma and one post
      irradiation fibrosarcoma. Apart from one patient with plasmocytoma and another
      one with non-Hodgkin lymphoma, the remaining four patients underwent partial or
      complete cleidectomy according to tumour location. At the time of latest follow
      up all patients were alive. Neither local recurrence nor metastases were observed
      in patients that underwent cleidectomy. In this group, the average score was
      86.6% of the expected normal function according to the Musculoskeletal Tumour
      Society (MSTS) evaluation form. The mean Constant-Murley score of the affected
      side was 80. Patients after cleidectomy were pain free, they had almost full
      shoulder range of motion and no significant functional deficit was reported.
      Primary malignant clavicular tumours may be easily undiagnosed due to their
      insidious clinical onset. Partial or total cleidectomy is associated with
      adequate shoulder mobility and mild functional deficit. Therefore, the extent of
      clavicle excision during tumour removal does not seem to determine the functional
      outcome of the affected shoulder.

PMID- 21188397
TI  - Perioperative cardiopulmonary complications after cervical spine surgery in the
      prone position: the relationship between age and preoperative testing.
AB  - BACKGROUND: Cardiac arrest during spine surgery in the prone position is
      difficult to manage as poor access makes cardiopulmonary resuscitation and
      defibrillation difficult. Advanced age is the maximal risk factor for cardiac
      arrest. Therefore, we wanted to determine the relationship between age and
      cardiac risk factors/pre-operating tests for cervical spine surgery in the prone
      position. METHODS: The inclusion criteria for this study specified 88 patients
      scheduled should undergo cervical spine surgery in the prone position. The
      patients were divided into two groups: Paients in group A (50 patients) were aged
      69 and under, Group B (38 patients) 70 and above. All patients responded to a
      medical interview about eight cardiac risk factors including past history, chest
      symptoms, diabetes mellitus, hypertension, hyperlipidemia, obesity, smoking, and
      family history. All patients underwent physical examination and 24-h Holter ECG
      and echocardiography performed by two cardiologists before surgery. We analyzed
      relationships between cardiac risk factors and ECG/echocardiography and
      investigated intra- and postoperative cardiovascular complications. RESULTS:
      Although there were no significant differences in the number of cardiac risk
      factors between the two groups, the frequency of hypertension was significantly
      greater in Group B than in Group A. The frequency of abnormal ECG and
      echocardiography findings especially was significantly greater in Group B than in
      Group A. In ECG and echocardiography, three patients in Group B who had no
      cardiac risk factors before surgery showed abnormal findings, and one of the
      three patients had the amalgamation of arrhythmia after the operation. Also, in
      Group B, cardiovascular complications occurred in one case during operation.
      CONCLUSION: These results suggested that patients aged 70 and above should
      undergo ECG and echocardiography examination before cervical spine surgery in the
      prone position whether they have cardiac risk factors or not . A prospective,
      randomized multi-center study with a larger patient sample is warranted to
      ultimately demonstrate how patients should be tested before spine surgery in the
      prone position.

PMID- 21188398
TI  - Synergistic effects of galectin-1 and reactive astrocytes on functional recovery
      after contusive spinal cord injury.
AB  - INTRODUCTION: Galectin-1 (Gal-1), a carbohydrate-binding protein, is
      differentially expressed by various normal and pathological tissues and appears
      to be functionally polyvalent. Recent evidence indicates that Gal-1 is involved
      in the proliferation of adult neural progenitor cells in neurogenic regions
      during adulthood. However, localization and functional roles of Gal-1 in the
      adult spinal cord have not been clarified. METHOD: Here, we investigated the
      spatio-temporal profile of endogenous Gal-1 expression by in situ hybridization
      before and after experimental adult spinal cord injury and examined the
      correlation of Gal-1 with the fate of dividing cells in vivo, using double
      labeling methods. Gal-1 mRNA was detectable at a relatively low level in
      uninjured spinal cord, but was markedly increased in the gray matter and/or white
      matter and in the ependyma rostral and caudal to the lesion site after injury.
      RESULTS: Co-localization results revealed that Gal-1 was expressed predominantly
      by GFAP-positive reactive astrocytes. In addition, intrathecal infusion of
      recombinant Gal-1 enhanced cell division and reactive astrocytosis in the adult
      spinal cord. To explore further whether Gal-1 and reactive astrocytes provide a
      synergistic effect on neurological recovery following SCI, we investigated the
      differences in behavioral analysis between wild-type (WT) and reactive astrocyte
      deficient transgenic mice after injury and found neuroprotective effects of Gal-1
      appeared to be specifically mediated through reactive astrocytes. CONCLUSION:
      These results indicate that Gal-1 exhibits great potential as a novel
      neuroprotective agent for the treatment of SCI.

PMID- 21188399
TI  - Percutaneous iliosacral screw fixation in S1 and S2 for posterior pelvic ring
      injuries: technique and perioperative complications.
AB  - OBJECTIVE: Percutaneous iliosacral screw placement allows for minimally invasive
      fixation of posterior pelvic ring instabilities. The objective of this study was
      to describe the technique for screws in S1 and S2 using conventional C-arm and to
      evaluate perioperative complications. METHODS: Thirty-eight consecutive patients
      after percutaneous pelvic ring fixation with cannulated screws in S1 and S2 using
      conventional C-arm fluoroscopy were analysed. Accuracy of screw placement, nerval
      lesions, need for second surgery, operation time, and time to full weight bearing
      were assessed postoperatively and during regular follow-up examinations. RESULTS:
      Twenty-one patients underwent unilateral screw fixation and 17 patients underwent
      bilateral screw fixation. In total, 83 screws were placed. Mean age of the
      patients was 52 +/- 19 years. Mean operation time was 16 +/- 7 min/screw. Mean
      follow-up was 5 +/- 3 months. Time to full weight bearing in 28 patients was 9 +/
      4 weeks. Eight patients were still not able to support full weight bearing,
      partially due to concomitant injuries. Patients without concomitant injuries that
      affected walking were able to bear full weight after 8 +/- 4 weeks (n = 17). Two
      patients had persistent postoperative hypaesthesia. No motor weakness was
      apparent and no postoperative bleeding was observed. Secondary surgery due to
      screw malpositioning or loosening had to be performed in four patients. The
      presence of a screw in S2 was not indicated for perioperative complications.
      CONCLUSIONS: Percutaneous iliosacral screw fixation is a rapid and definitive
      treatment for posterior pelvic ring injuries with a low risk of secondary
      bleeding during posterior pelvic stabilization. The technique using standard C
      arm fluoroscopy was also found to be safe for screws placed in S2.

PMID- 21188400
TI  - Responsiveness of urogynecologic quality of life measurements to change after
      radical gynecologic surgery.
AB  - AIM: In order to assess the responsiveness of short forms of the Incontinence
      Impact Questionnaire (IIQ-7) and Urogenital Distress Inventory (UDI-6) in a
      subset of women undergoing radical operations for gynecologic cancer. MATERIALS
      AND METHODS: Women with cervical cancer without any abnormal urodynamic
      abnormalities who had undergone Class III hysterectomy were included in the
      study. All women underwent urodynamic investigation and completed the IIQ-7 and
      UDI-6 questionnaires pre-operatively and post-operatively in the sixth month.
      Twenty-eight patients were enrolled and general and subscale scores of the
      questionnaire were calculated in the study between February 2008 and September
      2008. RESULTS: Class III hysterectomy was performed in 28 women with stage Ib
      cervical carcinoma. Scores of IIQ-7 and the irritative and obstructive subscales
      of UDI-6 in the sixth post-operative month were significantly higher than the pre
      operative scores. The Cronbach's alpha was 0.84. Cystometric parameters were in
      concordance with these changes in the questionnaire scores. CONCLUSION: The IIQ-7
      and UDI-6 questionnaires are sensitive to changes in patients who have undergone
      radical oncologic operations because their life impact of incontinence may be
      affected. Validated questionnaires are reasonable measures to detect these
      changes, which are confirmed by urodynamic findings.

PMID- 21188401
TI  - Pregnancy outcome in late maternal age in a high-income developing country.
AB  - AIM: This study aimed to compare the pregnancy outcome at maternal age 35 years
      and above with those aged between 20 and 34 years in a high-income developing
      country. METHODS: In this prospective study, pregnant women that delivered at Al
      Ain Hospital from the 1st April 2009 till 30th September 2009 were included. The
      obstetrical and perinatal outcome of mothers aged between 20 and 34 years and
      those aged 35 years old and above was compared. RESULTS: There were a total of
      888 patients. 699/888 (78.7%) were aged between 20 and 34 years and 189 (21.3%)
      were aged 35 years and above. Advanced maternal age was significantly associated
      with a higher incidence of type II diabetes mellitus (p = 0001), hypothyroidism
      (p = 0.02), history of miscarriages (p = 0.0001), GDM (p = 0.0001), placenta
      previa p = 0.04, induction of labor (p = 0.04), and Cesarean section (p = 0.009).
      CONCLUSION: Pregnant women at 35 years and above have higher incidence of
      gestational diabetes mellitus, placenta previa, and operative delivery. However,
      perinatal outcome are comparable to younger mothers.

PMID- 21188402
TI  - Genetic aspects of premature ovarian failure: a literature review.
AB  - BACKGROUND: The diagnosis of premature ovarian failure (POF) is based on the
      finding of amenorrhea before the age of 40 years associated with follicle
      stimulating hormone levels in the menopausal range. It is a heterogeneous
      disorder affecting approximately 1% of women <40 years, 1:10,000 women by age 20
      years and 1:1,000 women by age 30 years. POF is generally characterized by low
      levels of gonadal hormones (estrogens and inhibins) and high levels of
      gonadotropins (LH and FSH) (hypergonadotropic amenorrhea). METHODS: Review of
      significant articles regarding genetic causes that are associated with POF.
      RESULTS: Heterogeneity of POF is reflected by a variety of possible causes,
      including autoimmunity, toxics, drugs, as well as genetic defects. Changes at a
      single autosomal locus and many X-linked loci have been implicated in women with
      POF. X chromosome abnormalities (e.g., Turner syndrome) represent the major cause
      of primary amenorrhea associated with ovarian dysgenesis. Many genes have been
      involved in POF development, among them BMP15, FMR1, FMR2, LHR, FSHR, INHA,
      FOXL2, FOXO3, ERalpha, SF1, ERbeta and CYP19A1 genes. CONCLUSION: Despite the
      description of several candidate genes, the cause of POF remains undetermined in
      the vast majority of cases.

PMID- 21188403
TI  - Fetal cardiac function assessed by spatio-temporal image correlation.
AB  - BACKGROUND: Three-dimensional (3D) and four-dimensional (4D) ultrasound have been
      proposed to be valuable tools for the examination of fetal heart. Spatio-temporal
      image correlation (STIC) is a technique that adds a time component to 3D
      ultrasound imaging of the fetal heart, so we can evaluate cardiac structures as a
      4D cine sequence containing information of one full cardiac cycle. STIC gives the
      investigator the opportunity to freeze the displayed cardiac loop in end
      diastolic and end-systolic phases. By STIC, 3D measurements of both the left and
      right ventricle can be used to calculate fetal heart stroke volume, cardiac
      output and ejection fraction, and expressions of cardiac function. The ultimate
      goal of STIC technique is to improve fetal cardiac function analysis by
      decreasing the dependency on operator skills required by two-dimensional
      ultrasound. CONTEXT: In this article, we describe literature practical approach
      for the examination of the fetal heart function using 4D ultrasound by STIC
      technique.

PMID- 21188404
TI  - Comparison of Pap smear, visual inspection with acetic acid, and digital
      cervicography as cervical screening strategies.
AB  - PURPOSE: To compare the sensitivity, specificity, positive and negative
      predictive values (PPV and NPV), and accuracy of Pap smear, visual inspection
      with acetic acid (VIA) and digital cervicography (DC). METHODS: This is a cross
      sectional study on 100 women in the age group of 20-60 years, sequentially using
      the Pap test, the VIA, and the DC for screening. All women underwent colposcopic
      biopsy as the gold standard in comparing the methods. RESULTS: Of the total of
      100 women with the mean age 36.0 years, 17 cases were recognized positive for
      abnormal cervical cell by gold standard. The sensitivity, specificity, PPV, NPV,
      and accuracy of the Pap test, the VIA, and the DC were 23.5, 100, 100, 86.5, and
      87%; 62.5, 98.8, 90.9, 93.2, and 92.9%; and 46.7, 97.6, 77.8, 91, and 89.8%,
      respectively, for cervical neoplasia. CONCLUSIONS: The Pap test had low
      sensitivity but high specificity, whereas VIA had a high sensitivity in addition
      to being easy and low-cost. Adjuvant methods of screening such as VIA can be a
      valuable alternative to the Pap test for cervical cancer screening in low
      resource settings.

PMID- 21188405
TI  - Different gray matter patterns in chronic schizophrenia and chronic bipolar
      disorder patients identified using voxel-based morphometry.
AB  - Gray matter (GM) volume deficits have been described in patients with
      schizophrenia (Sz) and bipolar disorder (BD), but to date, few studies have
      directly compared GM volumes between these syndromes with methods allowing for
      whole-brain comparisons. We have used structural magnetic resonance imaging (MRI)
      and voxel-based morphometry (VBM) to compare GM volumes between 38 Sz and 19 BD
      chronic patients. We also included 24 healthy controls. The results revealed a
      widespread cortical (dorsolateral and medial prefrontal and precentral) and
      cerebellar deficit as well as GM deficits in putamen and thalamus in Sz when
      compared to BD patients. Besides, a subcortical GM deficit was shown by Sz and BD
      groups when compared to the healthy controls, although a putaminal reduction was
      only evident in the Sz patients. In this comparison, the BD patients showed a
      limited cortical and subcortical GM deficit. These results support a partly
      different pattern of GM deficits associated to chronic Sz and chronic BD, with
      some degree of overlapping.

PMID- 21188406
TI  - Ropinirole improves depressive symptoms and restless legs syndrome severity in
      RLS patients: a multicentre, randomized, placebo-controlled study.
AB  - Comorbid depressive symptoms in restless legs syndrome (RLS) remain a treatment
      challenge, as some antidepressants aggravate RLS symptoms. Preliminary data in
      depressive patients suggest antidepressant properties of ropinirole. The present
      study investigates the effects of ropinirole immediate release (IR) on depressive
      symptoms and RLS severity. A multicenter, placebo-controlled, double-blind
      randomized (3:1) study was performed including patients with moderate to severe
      idiopathic RLS and at least mild depressive symptoms. Ropinirole IR (in flexible
      doses up to 4 mg/day) or placebo was given for 12 weeks including an uptitration
      phase of 7 weeks. Visits were scheduled at screening, baseline, and weeks 1, 4,
      and 12 with additional telephone contacts for dosing decisions. The modified
      intent to treat population comprised 231 patients (171 ropinirole, 60 placebo).
      The MADRS (Montgomery-Asberg Depression Rating Scale) scores decreased from
      baseline to week 12 from 18.8 to 8.7 in the ropinirole group and from 18.4 to
      12.1 in the placebo group (primary endpoint, adjusted mean treatment difference 
      3.6 (95% CI: -5.6 to -1.6, significance in favor of ropinirole: P < 0.001). The
      superiority of ropinirole compared to placebo was confirmed by the Hamilton Scale
      for Depression and Beck Depression Inventory-II scores. RLS severity scores
      (IRLS) decreased by 14.7 (ropinirole) and by 9.9 (placebo, P < 0.001) points.
      Three out of four subdomains of the Medical Outcomes Study Sleep Scale improved
      significantly. The findings indicate that mild to moderate depressive symptoms
      should not be treated before sufficient therapy for RLS. Antidepressant
      medication can be necessary if depression symptoms still persist even if RLS
      symptoms are ameliorated.

PMID- 21188407
TI  - The association between motor subtypes and alexithymia in de novo Parkinson's
      disease.
AB  - This study aimed at investigating the association between motor subtypes and
      alexithymic features in patients with newly diagnosed untreated (de novo)
      Parkinson's disease. This objective derived from empirical findings about an
      association between the postural instability/gait difficulty motor subtype of
      Parkinson's disease and more marked symptoms of depression, an affective disorder
      strongly related to alexithymia. A total of 42 patients with de novo Parkinson's
      disease underwent neuropsychiatric assessment, including the toronto alexithymia
      scale (TAS-20) and the geriatric depression scale (GDS-15). On the basis of
      scores reported at the unified Parkinson's disease rating scale III section,
      patients were classified within postural instability/gait difficulty motor
      subtype tremor dominant motor subtype and mixed motor subtype. Patients of the
      postural instability/gait difficulty motor subtype reported significantly higher
      alexithymic features compared to patients of the other motor subtypes.
      Considering the strong association between alexithymia and depression, this
      finding is in line with previous findings reporting that the postural
      instability/gait difficulty subtype of Parkinson's disease is associated to more
      marked psychopathological features, especially affective features (depression and
      apathy). In conclusion this brief report suggests the usefulness of an early
      neuropsychiatric assessment of affect regulation difficulties in PD patients,
      especially in those with a prevalence of akinetic/rigid symptoms.

PMID- 21188408
TI  - Summary of cerebrospinal fluid routine parameters in neurodegenerative diseases.
AB  - In neurodegenerative diseases, cerebrospinal fluid analysis (CSF) is
      predominantly performed to exclude inflammatory diseases and to perform a risk
      assessment in dementive disorders by measurement of tau proteins and amyloid beta
      peptides. However, large scale data on basic findings of CSF routine parameters
      are generally lacking. The objective of the study was to define a normal
      reference spectrum of routine CSF parameters in neurodegenerative diseases.
      Routine CSF parameters (white cell count, lactate and albumin concentrations,
      CSF/serum quotients of albumin (Q (alb)), IgG, IgA, IgM, and oligoclonal IgG
      bands (OCB)) were retrospectively analyzed in an academic research setting. A
      total of 765 patients (Alzheimer's disease (AD), Parkinson's disease (PD),
      Parkinson's disease dementia (PDD), vascular dementia (VD), frontotemporal lobar
      degeneration (FTLD), progressive supranuclear palsy (PSP), multisystem atrophy
      (MSA), motor neuron diseases (MND), spinocerebellar ataxia (SCA), Huntington's
      disease (HD)) and non-demented control groups including a group of patients with
      muscular disorders (MD). The main outcome measures included statistical analyses
      of routine CSF parameters. Mildly elevated Q (alb) were found in a small
      percentage of nearly all subgroups and in a higher proportion of patients with
      PSP, MSA, VD, PDD, and MND. With the exception of 1 MND patient, no intrathecal
      Ig synthesis was observed. Isolated OCBs in CSF were sometimes found in patients
      with neurodegenerative diseases without elevated cell counts; lactate levels were
      always normal. A slightly elevated Q (alb) was observed in a subgroup of patients
      with neurodegenerative diseases and does not exclude the diagnosis. Extensive
      elevation of routine parameters is not characteristic and should encourage a re
      evaluation of the clinical diagnosis.

PMID- 21188409
TI  - Interobserver agreement in ABCD scoring between non-stroke specialists and
      vascular neurologists following suspected TIA is only fair.
AB  - The appropriateness of use and accuracy of age, blood pressure, clinical features
      and duration of symptoms (ABCD) scoring by non-stroke specialists while risk
      stratifying patients with suspected transient ischaemic attack (TIA) are unknown.
      We reviewed all available ABCD data from referrals to a specialist neurovascular
      clinic. ABCD scoring was defined as 'appropriate' in this study if an experienced
      vascular neurologist subsequently confirmed a clinical diagnosis of possible,
      probable or definite TIA, and 'inappropriate' if the patient had an alternative
      diagnosis or stroke. Interobserver agreement between the referring physician and
      the neurologist was calculated. One hundred and four patients had completed ABCD
      referral proformas available for analysis. Forty-five (43%) were deemed
      appropriate, and 59 (57%) inappropriate. In the entire dataset, the neurologist
      agreed with the referring physician's total ABCD score in only 42% of cases
      [kappa = 0.28]. The two most unreliable components of the scoring system were
      clinical features [kappa = 0.51], and duration of symptoms [kappa = 0.48]. ABCD
      scoring by non-stroke specialists is frequently inappropriate and inaccurate in
      routine clinical practice, emphasising the importance of urgent specialist
      assessment of suspected TIA patients.

PMID- 21188410
TI  - Eccentric stimulation reveals an involvement of FGF6 in muscle resistance to
      mechanical stress.
AB  - The objective of this report was to analyse a potential role for FGF6 in muscle
      resistance to mechanical stress. Normal or regenerating muscles of FGF6 (-/-)
      mice versus wild-type mice were submitted to different protocols of damaging
      eccentric contractions (eccentric electrostimulation and intermittent downhill
      exercise). Then muscular structural properties were analysed by histological and
      immunochemistry techniques to evaluate the post-injury muscle recovery; their
      muscle contractile parameters (maximal tetanic force, kinetics properties and
      fatigue resistance) were assessed. The absence of FGF6 causes (1) a fast-to-slow
      myofibre type switch in adult control and regenerating Tibialis anterior (TA)
      muscle; (2) muscle weakness in regenerating muscles in animals submitted to
      eccentric exercise protocols due to aberrant extensive necrotic zones. These
      observations point out a crucial and unexpected role for FGF6 in muscle integrity
      and muscle protection against mechanical stress.

PMID- 21188411
TI  - The unfolded protein response in human skeletal muscle is not involved in the
      onset of glucose tolerance impairment induced by a fat-rich diet.
AB  - Endoplasmic reticulum (ER) stress in pancreas, liver, and adipose tissue is a key
      event in the pathogenesis of obesity-related metabolic disease. Lipid-induced ER
      stress in liver and adipose tissue leads to inhibition of insulin signaling.
      Whether this mechanism exists in skeletal muscle is currently unknown. The
      present study aimed at assessing the ER stress response in skeletal muscle of
      subjects receiving a hyper-caloric fat-rich diet (HFD). Seven healthy males (20.6
      +/- 0.5 years; 70.9 +/- 3.4 kg) volunteered to participate in the study. They
      received a hyper-caloric (+30% kcal) fat-rich (50% kcal) diet for 6 weeks. An
      oral glucose tolerance test (OGTT) was performed, and muscle biopsies were taken
      before and after HFD. HFD increased body mass by ~3 kg (P = 0.007) and the sum of
      skinfolds by 15% (P = 0.003). After HFD, blood glucose concentrations were higher
      during OGTT (two-way ANOVA, P = 0.023; +45% at 20 min, P = 0.002), and fasting
      plasma insulin level tended to be higher (+20%). HFD increased intramyocellular
      lipids content by ~50 and 75% in type I (P = 0.0009) and IIa fibers (P = 0.002),
      respectively. The protein expression of inositol-requiring enzyme 1alpha, protein
      kinase R-like ER protein kinase, BiP and calnexin and the mRNA level of spliced X
      box binding protein-1, CCAAT/enhancer binding protein homologous protein and
      activating transcription factor 4 were not changed after HFD. Despite the
      increase in body mass, subcutaneous fat deposits, and intramyocellular lipids
      content, ER stress markers were unchanged in skeletal muscle of subjects
      receiving a HFD for 6 weeks. This suggests that the onset of glucose intolerance
      is not related to ER stress in skeletal muscle.

PMID- 21188412
TI  - Neuromuscular function following prolonged intense self-paced exercise in hot
      climatic conditions.
AB  - Muscle weakness following constant load exercise under heat stress has been
      associated with hyperthermia-induced central fatigue. However, evidence of
      central fatigue influencing intense self-paced exercise in the heat is lacking.
      The purpose of this investigation was to evaluate force production capacity and
      central nervous system drive in skeletal muscle pre- and post-cycle ergometer
      exercise in hot and cool conditions. Nine trained male cyclists performed a 20-s
      maximal voluntary isometric contraction (MVC) prior to (control) and following a
      40-km time trial in hot (35 degrees C) and cool (20 degrees C) conditions. MVC
      force production and voluntary activation of the knee extensors was evaluated via
      percutaneous tetanic stimulation. In the cool condition, rectal temperature
      increased to 39.0 degrees C and reached 39.8 degrees C in the heat (P < 0.01).
      Following exercise in the hot and cool conditions, peak force declined by ~90 and
      ~99 N, respectively, compared with control (P < 0.01). Mean force decreased by
      15% (hot) and 14% (cool) (P < 0.01 vs. control). Voluntary activation during the
      post-exercise MVC declined to 93.7% (hot) and 93.9% (cool) (P < 0.05 vs.
      control). The post-exercise decline in voluntary activation represented ~20% of
      the decrease in mean force production in both conditions. Therefore, the
      additional increase in rectal temperature did not exacerbate the loss of force
      production following self-paced exercise in the heat. The impairment in force
      production indicates that the fatigue exhibited by the quadriceps is mainly of
      peripheral origin and a consequence of the prolonged contractile activity
      associated with exercise.

PMID- 21188413
TI  - Skin advanced glycation end product accumulation and muscle strength among adult
      men.
AB  - Aging is associated with decreased skeletal muscle function. Increased levels of
      advanced glycation end products (AGEs) in skeletal muscle tissue are observed
      with advancing age and in diabetes. Although serum AGE level is negatively
      associated with grip strength in elderly people, it is unknown whether this
      association is present in adult males. To determine the relationship between AGE
      accumulation in tissue and muscle strength and power among Japanese adult men.
      Skin autofluorescence (AF) (a noninvasive method for measuring tissue AGEs), grip
      strength (n = 232), and leg extension power (n = 138) were measured in Japanese
      adult men [median (interquartile range) age, 46.0 (37.0, 56.0) years]. After
      adjustment for potential confounders, the adjusted means [95% confidence interval
      (CI)] for grip strength across the tertiles of skin AF were 44.5 (43.2, 45.9) kg
      for the lowest tertile, 42.0 (40.6, 43.3) kg for the middle tertile, and 41.7
      (40.3, 43.1) kg for the highest tertile (P for trend < 0.01). Moreover, the
      adjusted geometric means (95% CI) of leg extension power across the tertiles of
      skin AF were 17.8 (16.6, 19.1) W/kg for the lowest tertile, 17.5 (16.4, 18.7)
      W/kg for the middle tertile, and 16.0 (14.9, 17.1) W/kg for the highest tertile
      (P for trend = 0.04). Among Japanese adult men, participants with higher skin AF
      had lower muscle strength and power, indicating a relationship between AGE
      accumulation and muscle strength and power. A long-term prospective study is
      required to clarify the causality.

PMID- 21188414
TI  - Instantaneous changes in heart rate regulation due to mental load in simulated
      office work.
AB  - The cardiac regulation effects of a mental task added to regular office work are
      described. More insight into the time evolution during the different tasks is
      created by using time-frequency analysis (TFA). Continuous wavelet transformation
      was applied to create time series of instantaneous power and frequency in
      specified frequency bands (LF 0.04-0.15 Hz; HF 0.15-0.4 Hz), in addition to the
      traditional linear heart rate variability (HRV) parameters. In a laboratory
      environment, 43 subjects underwent a protocol with three active conditions: a
      clicking task with low mental load and a clicking task with high mental load
      (mental arithmetic) performed twice, each followed by a rest condition. The heart
      rate and measures related to vagal modulation could differentiate the active
      conditions from the rest condition, meaning that HRV is sensitive to any change
      in mental or physical state. Differences between physical and mental stress were
      observed and a higher load in the combined task was observed. Mental stress
      decreased HF power and caused a shift toward a higher instantaneous frequency in
      the HF band. TFA revealed habituation to the mental load within the task (after 3
      min) and between the two tasks with mental load. In conclusion, the use of TFA in
      this type of analysis is important as it reveals extra information. The addition
      of a mental load to a physical task elicited further effect on HRV parameters
      related to autonomic cardiac modulation.

PMID- 21188415
TI  - Comparison of maximal unilateral versus bilateral voluntary contraction force.
AB  - The aim of the present study was to determine whether the difference in maximal
      voluntary contraction (MVC) forces between unilateral (UL) and bilateral (BL)
      contractions could be due to a difference in the timing of MVC peak force
      production between legs during BL MVC, or due to the maximal voluntary activation
      level (VAL) in each leg between UL and BL MVC. Thirteen active men (28 +/- 6
      years) volunteered to participate in an experimental session requiring the
      performance of MVC with right, left and both knee extensor muscles. An ergometer
      equipped with two strain gauges was used to assess the timing of MVC peak force
      production of each leg during BL MVC. Transcutaneous electrical stimulation was
      used to investigate VAL and electromyography (EMG) activity. The present results
      showed that the sum of the right and left UL MVC was higher compared to BL MVC
      force, i.e., a BL deficit of force. The timing of MVC peak force production of
      each leg during BL MVC was not different, but BL MVC force was lower than the sum
      of BL MVC(R) and BL MVC(L) force (i.e., maximal force production of each leg
      during BL MVC). No changes of EMG activity, M-wave amplitude, VAL, and peak
      doublet between UL and BL contractions were observed. The difference found in the
      production of force during BL MVC cannot be explained by the timing of force
      production of each leg.

PMID- 21188416
TI  - Molecular iodine emission rates and photosynthetic performance of different
      thallus parts of Laminaria digitata (Phaeophyceae) during emersion.
AB  - The emission of molecular iodine (I(2)) from the stipe, the meristematic area and
      the distal blade of the brown macroalga Laminaria digitata (Hudson) Lamouroux
      (Phaeophyceae) was monitored under low light and dark conditions. Photosynthetic
      parameters were determined to investigate both the extent of stress experienced
      by different thallus parts and the effects of emersion on photosynthesis.
      Immediately after air exposure, intense I(2) emission was detectable from all
      thallus parts. I(2) emission declined continuously over a period of 180 min
      following the initial burst, but was not affected by the light regime. The total
      number of mole of I(2) emitted by stipes was approximately 10 times higher than
      those emitted from other thallus parts. Initial I(2) emission rates (measured
      within 30 min of exposure to air) were highest for stipes (median values: 2,999
      and 5,222 pmol g(-1) dw min(-1) in low light and dark, respectively) and lower,
      by one order of magnitude, for meristematic regions and distal blades. After
      exposure to air for between 60 and 180 min, I(2) emission rates of all thallus
      parts were reduced by 70-80%. Air exposure resulted in a decrease of the maximum
      photosystem II (PSII) efficiency (F(v)/F(m)) by 3%, and in a 25-55% increase of
      the effective PSII quantum efficiency (F(v)/F'(m)); this was caused by a higher
      fraction of open reaction centres (q(P)), whereas the efficiency of the latter in
      capturing energy (F'(v)/F'(m)) remained constant. The results indicate the
      presence of an iodine pool which is easily volatilised and depleted due to air
      exposure, even under apparently low stress conditions.

PMID- 21188417
TI  - DNA repair defects sensitize cells to anticodon nuclease yeast killer toxins.
AB  - Killer toxins from Kluyveromyces lactis (zymocin) and Pichia acaciae (PaT) were
      found to disable translation in target cells by virtue of anticodon nuclease
      (ACNase) activities on tRNA(Glu) and tRNA(Gln), respectively. Surprisingly,
      however, ACNase exposure does not only impair translation, but also affects
      genome integrity and concomitantly DNA damage occurs. Previously, it was shown
      that homologous recombination protects cells from ACNase toxicity. Here, we have
      analyzed whether other DNA repair pathways are functional in conferring ACNase
      resistance as well. In addition to HR, base excision repair (BER) and
      postreplication repair (PRR) promote clear resistance to either, PaT and zymocin.
      Comparative toxin sensitivity analysis of BER mutants revealed that its ACNase
      protective function is due to the endonucleases acting on apurinic (AP) sites,
      whereas none of the known DNA glycosylases is involved. Because PaT and zymocin
      require the presence of the ELP3/TRM9-dependent wobble uridine modification 5
      methoxy-carbonyl-methyl (mcm(5)) for tRNA cleavage, we analyzed toxin response in
      DNA repair mutants additionally lacking such tRNA modifications. ACNase
      resistance caused by elp3 or trm9 mutations was found to rescue hypersensitivity
      of DNA repair defects, consistent with DNA damage to occur as a consequence of
      tRNA cleavage. The obtained genetic evidence promises to reveal new aspects into
      the mechanism linking translational fidelity and genome surveillance.

PMID- 21188418
TI  - Novel mutations in the keratin-74 (KRT74) gene underlie autosomal dominant woolly
      hair/hypotrichosis in Pakistani families.
AB  - Autosomal dominant woolly hair (ADWH) is an inherited condition of tightly curled
      and twisted scalp hair. Recently, a mutation in human keratin-74 (KRT74) gene has
      been shown to cause this form of hereditary hair disorder. In the present study,
      we have described two families (A and B) having multiple individuals affected
      with autosomal dominant form of hair loss disorders. In family A, 10 individuals
      showed ADWH phenotype while in the family B, 14 individuals showed hypotrichosis
      of the scalp. Genotyping using polymorphic microsatellite markers showed linkage
      of both the families to type II keratin gene cluster on the chromosome 12q12
      14.1. Mutation analysis of the KRT74 gene identified two novel mutations in the
      affected individuals of the families. The sequence analysis revealed a splice
      acceptor site mutation (c.IVS8-1G>A) in family A and a missense variant
      (c.1444G>A, p.Asp482Asn) in family B. Mutations identified in the present study
      extend the body of evidence implicating the KRT74 gene in the pathogenesis of
      autosomal dominant hair loss disorders.

PMID- 21188419
TI  - Distribution of the number of false discoveries in large-scale family-based
      association testing with application to the association between PTPN1 and
      hypertension and obesity.
AB  - We present a model-free approach to the study of the number of false discoveries
      for large-scale simultaneous family-based association tests (FBATs) in which the
      set of discoveries is decided by applying a threshold to the test statistics.
      When the association between a set of markers in a candidate gene and a group of
      phenotypes is studied by a class of FBATs, we indicate that a joint null
      hypothesis distribution for these statistics can be obtained by the fundamental
      statistical method of conditioning on sufficient statistics for the null
      hypothesis. Based on the joint null distribution of these statistics, we can
      obtain the distribution of the number of false discoveries for the set of
      discoveries defined by a threshold; the size of this set is referred to as its
      tail count. Simulation studies are presented to demonstrate that the conditional,
      not the unconditional, distribution of the tail count is appropriate for the
      study of false discoveries. The usefulness of this approach is illustrated by re
      examining the association between PTPN1 and a group of blood-pressure-related
      phenotypes reported by Olivier et al. (Hum Mol Genet 13:1885-1892, 2004); our
      results refine and reinforce this association.

PMID- 21188420
TI  - Natural selection at genomic regions associated with obesity and type-2 diabetes:
      East Asians and sub-Saharan Africans exhibit high levels of differentiation at
      type-2 diabetes regions.
AB  - Different populations suffer from different rates of obesity and type-2 diabetes
      (T2D). Little is known about the genetic or adaptive component, if any, that
      underlies these differences. Given the cultural, geographic, and dietary
      variation that accumulated among humans over the last 60,000 years, we examined
      whether loci identified by genome-wide association studies for these traits have
      been subject to recent selection pressures. Using genome-wide SNP data on 938
      individuals in 53 populations from the Human Genome Diversity Panel, we compare
      population differentiation and haplotype patterns at these loci to the rest of
      the genome. Using an "expanding window" approach (100-1,600 kb) for the
      individual loci as well as the loci as ensembles, we find a high degree of
      differentiation for the ensemble of T2D loci. This differentiation is most
      pronounced for East Asians and sub-Saharan Africans, suggesting that these groups
      experienced natural selection at loci associated with T2D. Haplotype analysis
      suggests an excess of obesity loci with evidence of recent positive selection
      among South Asians and Europeans, compared to sub-Saharan Africans and Native
      Americans. We also identify individual loci that may have been subjected to
      natural selection, such as the T2D locus, HHEX, which displays both elevated
      differentiation and extended haplotype homozygosity in comparisons of East Asians
      with other groups. Our findings suggest that there is an evolutionary genetic
      basis for population differences in these traits, and we have identified
      potential group-specific genetic risk factors.

PMID- 21188422
TI  - Optimization of nitrilase production from Alcaligenes faecalis MTCC 10757 (IICT
      A3): effect of inducers on substrate specificity.
AB  - Microbial nitrilases are biocatalysts of interest and the enzyme produced using
      various inducers exhibits altered substrate specificity, which is of great
      interest in bioprocess development. The aim of the present study is to
      investigate the nitrilase-producing Alcaligenes faecalis MTCC 10757 (IICT-A3) for
      its ability to transform various nitriles in the presence of different inducers
      after optimization of various parameters for maximum enzyme production and
      activity. The production of A. faecalis MTCC 10757 (IICT-A3) nitrilase was
      optimum with glucose (1.0%), acrylonitrile (0.1%) at pH 7.0. The nitrilase
      activity of A. faecalis MTCC 10757 (IICT-A3) was optimum at 35  degrees C, pH 8.0
      and the enzyme was stable up to 6 h at 50  degrees C. The nitrilase enzyme
      produced using different inducers was investigated for substrate specificity. The
      enzyme hydrolyzed aliphatic, heterocyclic and aromatic nitriles with different
      substitutions. Acrylonitrile was the most preferred substrate (~40 U) as well as
      inducer. Benzonitrile was hydrolyzed with almost twofold higher relative activity
      than acrylonitrile when it was used as an inducer. The versatile nitrilase
      producing A. faecalis MTCC 10757 (IICT-A3) exhibits efficient conversion of both
      aliphatic and aromatic nitriles. The aromatic nitriles, which show not much or no
      affinity towards nitrilase from A. faecalis, are hydrolyzed effectively with this
      nitrilase-producing organism. Studies are in progress to exploit this organism
      for synthesis of industrially important compounds.

PMID- 21188421
TI  - Quantitative characterization of metabolism and metabolic shifts during growth of
      the new human cell line AGE1.HN using time resolved metabolic flux analysis.
AB  - For the improved production of vaccines and therapeutic proteins, a detailed
      understanding of the metabolic dynamics during batch or fed-batch production is
      requested. To study the new human cell line AGE1.HN, a flexible metabolic flux
      analysis method was developed that is considering dynamic changes in growth and
      metabolism during cultivation. This method comprises analysis of formation of
      cellular components as well as conversion of major substrates and products,
      spline fitting of dynamic data and flux estimation using metabolite balancing.
      During batch cultivation of AGE1.HN three distinct phases were observed, an
      initial one with consumption of pyruvate and high glycolytic activity, a second
      characterized by a highly efficient metabolism with very little energy spilling
      waste production and a third with glutamine limitation and decreasing viability.
      Main events triggering changes in cellular metabolism were depletion of pyruvate
      and glutamine. Potential targets for the improvement identified from the analysis
      are (i) reduction of overflow metabolism in the beginning of cultivation, e.g.
      accomplished by reduction of pyruvate content in the medium and (ii) prolongation
      of phase 2 with its highly efficient energy metabolism applying e.g. specific
      feeding strategies. The method presented allows fast and reliable metabolic flux
      analysis during the development of producer cells and production processes from
      microtiter plate to large scale reactors with moderate analytical and
      computational effort. It seems well suited to guide media optimization and
      genetic engineering of producing cell lines.

PMID- 21188423
TI  - Membranoproliferative glomerulonephritis with C3NeF and genetic complement
      dysregulation.
AB  - The development of membranoproliferative glomerulonephritis (MPGN) is associated
      with uncontrolled activation of the complement alternative pathway. This
      dysregulation is related either to C3 nephritic factor (C3NeF), an auto-antibody
      directed against the alternative C3 convertase, or to homozygous loss-of-function
      mutation of the complement regulatory protein factor H. Heterozygous mutations in
      the genes coding for factor H, or for the other alternative pathway inhibitory
      proteins factor I and membrane cofactor protein, have recently been identified in
      a small number of patients with MPGN with exclusive C3 deposits. We report three
      hypocomplementemic children with dense deposit disease (n=1) or immune-complex
      mediated MPGN type I (n=2), associated with both C3NeF activity and heterozygous
      mutation of factor H or factor I. These observations highlight the possible
      combination of genetic and acquired defect in complement control in various
      subtypes of MPGN, a finding that may influence the treatment strategy in some
      patients.

PMID- 21188425
TI  - Prevention of chemotherapy- and radiotherapy-induced nausea and vomiting:
      guideline update and results of the Perugia consensus conference.

PMID- 21188424
TI  - Thermal comfort modelling of body temperature and psychological variations of a
      human exercising in an outdoor environment.
AB  - Human thermal comfort assessments pertaining to exercise while in outdoor
      environments can improve urban and recreational planning. The current study
      applied a simple four-segment skin temperature approach to the COMFA (COMfort
      FormulA) outdoor energy balance model. Comparative results of measured mean skin
      temperature ([Formula: see text]) with predicted [Formula: see text] indicate
      that the model accurately predicted [Formula: see text], showing significantly
      strong agreement (r = 0.859, P < 0.01) during outdoor exercise (cycling and
      running). The combined 5-min mean variation of the [Formula: see text] RMSE was
      1.5 degrees C, with separate cycling and running giving RMSE of 1.4 degrees C and
      1.6 degrees C, respectively, and no significant difference in residuals.
      Subjects' actual thermal sensation (ATS) votes displayed significant strong rank
      correlation with budget scores calculated using both measured and predicted
      [Formula: see text] (r ( s ) = 0.507 and 0.517, respectively, P < 0.01). These
      results show improved predictive strength of ATS of subjects as compared to the
      original and updated COMFA models. This psychological improvement, plus [Formula:
      see text] and T (c) validations, enables better application to a variety of
      outdoor spaces. This model can be used in future research studying linkages
      between thermal discomfort, subsequent decreases in physical activity, and
      negative health trends.

PMID- 21188426
TI  - Comparison of steroid pulse therapy and conventional oral steroid therapy as
      initial treatment for autoimmune pancreatitis.
AB  - BACKGROUND: The efficacy of oral steroid therapy for autoimmune pancreatitis
      (AIP) is well known, and oral prednisolone treatment is most usually commenced at
      30-40 mg/day, but there have been few reports about comparative studies of oral
      steroid therapy and steroid pulse therapy as the initial treatment for AIP. We
      studied the clinical course and image findings to estimate the utility of steroid
      pulse therapy for AIP, comparing it with oral steroid therapy. METHODS:
      Laboratory and image findings were assessed retrospectively in 11 patients who
      received steroid pulse therapy, and the findings were compared to those in 10
      patients who received conventional oral steroid therapy. RESULTS: Change in
      pancreatic size showed no significant difference between the therapies after 2
      weeks of treatment. Significant improvement of lower bile duct strictures after 2
      weeks of treatment and that of immunoglobulin values within 6 months were shown
      with both therapies. However, steroid pulse therapy showed significant
      improvement of gamma-guanosine triphosphate (GTP) in 2 weeks and of alanine
      aminotransferase (ALT) in 2 and 8 weeks, compared with oral steroid therapy.
      Moreover, there was one patient in whom the lower bile duct stricture was not
      improved by oral steroid therapy, but it did show improvement with steroid pulse
      therapy. CONCLUSIONS: Initial steroid pulse therapy is a beneficial alternative
      to oral steroid therapy for the improvement of bile duct lesions. In future, the
      accumulation of a larger number of patients receiving steroid pulse therapy is
      needed, and prospective studies will be required.

PMID- 21188427
TI  - Upper airway obstruction associated with flexed cervical position after posterior
      occipitocervical fusion.
AB  - Upper airway obstruction resulting from overflexion fixation of the cervical
      spine is a rare but life-threatening complication after cervical spine surgery.
      There are few reports of dyspnea after a posterior cervical fusion. We present
      the case of a 63-year-old woman with rheumatoid arthritis who developed an upper
      airway obstruction immediately after an O-C4 fusion. She was reintubated with a
      fiberoptic scope. Revision surgery allowing the angle to return to the neutral
      position was performed to ameliorate the overflexion of the cervical spine
      fixation and the consequent upper airway obstruction. After revision surgery, the
      upper airway obstruction disappeared. Our experience suggests that intraoperative
      use of fluoroscopy and extubation with a tube exchanger are recommended to avoid
      this complication, especially in patients at high risk of upper airway
      obstruction.

PMID- 21188428
TI  - Anti-hyperalgesic effect of CaMKII inhibitor is associated with downregulation of
      phosphorylated CREB in rat spinal cord.
AB  - PURPOSE: Calcium/calmodulin-dependent protein kinase (CaMK) II and its downstream
      effector cyclic adenosine monophosphate (cAMP) responsive element binding protein
      (CREB) may be involved in the development of neuropathic pain. The aim of this
      study was to examine the effect of the CaMKII inhibitor AIP on the association of
      CaMKII and CREB in a partial sciatic nerve ligation neuropathic pain model in
      rats. METHODS: Male Sprague-Dawley rats were randomly divided into six groups:
      Sham operation; partial sciatic nerve ligation (SNL); AIP administration prior to
      or after SNL; and normal saline (NS) administration prior to or after SNL. NS or
      10 MUmol/L AIP (10 MUl) were injected intrathecally in the NS group and AIP
      group, respectively, 20 min before or 4 days after nerve injury. The mechanical
      withdrawal threshold of the hindpaw was measured before and after SNL. In another
      cohort treated as above, the lumbar spinal cord was removed on post-surgery days
      1, 3, and 7 to detect the expression of phosphorylated CaMKII (pCaMKII) and
      phosphorylated CREB (pCREB), by in situ immunostaining and western blot,
      respectively. RESULTS: AIP significantly suppressed tactile allodynia in the SNL
      rats, and its effects lasted for 3 days when given prior to nerve injury. In
      contrast, it had a transitory effect when given after nerve injury. AIP decreased
      the expression of pCaMKII and pCREB and its effect was sustained for up to 3 days
      after the experiments. CONCLUSION: Intrathecal injection of a CaMKII inhibitor
      attenuated neuropathic pain. This benefit may have been due to the downmodulation
      of its downstream effector pCREB.

PMID- 21188429
TI  - Validation of inflationary non-invasive blood pressure monitoring in adult
      surgical patients.
AB  - Oscillometric determination of blood pressure may be advantageous, as cuff
      inflation requires lower cuff pressure and shorter duration than deflation. In
      this observational study, we compared the blood pressure value, cuff pressure,
      and duration of cuff inflation between a prototype of inflationary non-invasive
      blood pressure (NIBP) and conventional deflationary NIBP in adult patients during
      anesthesia. Three hundred and twenty-three pairs of measurements were obtained
      from 64 subjects. The bias and precision of systolic pressure and diastolic
      pressure were 2.9 +/- 8.3 and 5.6 +/- 6.1 mmHg, respectively. Inflationary NIBP
      could better determine NIBP with lower cuff pressure than deflationary NIBP (124
      +/- 22 vs. 160 +/- 33 mmHg, p < 0.05). Inflationary NIBP could also determine
      NIBP more quickly (13.0 +/- 2.3 vs. 32.7 +/- 13.6 s, p < 0.05). These data
      suggest that inflationary NIBP may reduce cuff-related discomfort and
      complications, and has reasonable accuracy compared to deflationary NIBP in adult
      surgical patients.

PMID- 21188431
TI  - Therapeutic strategy for acute respiratory distress syndrome: recent
      understanding of the pathophysiology of the disease.

PMID- 21188432
TI  - Study on airway smooth muscle tone using fiberoptic bronchoscopy: basic research
      and clinical application.

PMID- 21188434
TI  - Identification of the disulfide bonds of lysyl oxidase.
AB  - Proteolytic digestion of bovine aortic lysyl oxidase followed by tandem mass
      spectrometry has enabled assignment of all five disulfide bonds. The results
      indicate that the enzyme has a very stable central core containing three
      disulfide bonds, the lysyl tyrosyl quinone cross-link and the copper. This core
      is well isolated from solvent with the result that the oxidized (normal) form of
      the enzyme is remarkably resistant to proteolysis and is unusually stable at high
      temperatures and in the presence of denaturants.

PMID- 21188435
TI  - What is the best treatment for fluctuating Parkinson's disease: continuous drug
      delivery or deep brain stimulation of the subthalamic nucleus?
AB  - Motor complications impair quality of life and cause severe disability in
      patients with advanced Parkinson's disease (PD). Since they are often refractory
      to medical therapy, interventional therapies have been developed, which can
      provide a considerable reduction of daily off-time and dopaminergic dyskinesias.
      Continuous dopaminergic drug delivery (CDD) is based on the steady stimulation of
      striatal dopamine receptors by subcutaneous apomorphine or duodenal L: -DOPA
      infusions via portable minipumps. Advances in the understanding of basal ganglia
      functioning and in neurosurgical, electrophysiological and neuroimaging
      techniques have led to a renaissance of neurosurgery for advanced PD. Deep brain
      stimulation of the subthalamic nucleus (STN-DBS) is the most invasive procedure
      promising great benefit and the highest level of independency for suitable
      patients, but is definitely associated with surgical risks and DBS-related side
      effects. Each of these more or less invasive therapy options has its own profile,
      and a thorough consideration of its advantages and drawbacks for the individual
      situation is mandatory. In this paper, we summarize relevant facts for this
      decision and provide some guidelines for a responsible counseling of eligible
      patients.

PMID- 21188436
TI  - Transcriptional alterations under continuous or pulsatile dopaminergic treatment
      in dyskinetic rats.
AB  - Continuous dopaminergic treatment is considered to prevent or delay the
      occurrence of dyskinesia in patients with Parkinson's disease (PD). Rotigotine is
      a non-ergolinic D(3) > D(2) > D(1) dopamine-receptor agonist for the treatment of
      PD using a transdermal delivery system providing stable plasma levels. We aimed
      to investigate the differential influence on gene expression of pulsatile L: 
      DOPA or rotigotine versus a continuous rotigotine treatment. The gene expression
      profile within the nigro-striatal system of unilateral 6-hydroxydopamine-lesioned
      rats was assessed in order to differentiate potential changes in gene expression
      following the various treatment using Affymetrix microarrays and quantitative RT
      PCR. The expression of 15 genes in the substantia nigra and of 11 genes in the
      striatum was altered under pulsatile treatments inducing dyskinetic motor
      response, but was unchanged under continuous rotigotine treatment that did not
      cause dyskinetic motor response. The route of administration of a dopaminergic
      drug is important for the induction or prevention of motor abnormalities and
      adaptive gene expressions. The decline of neurotrophin-3 expression under
      pulsatile administration was considered of particular importance.

PMID- 21188437
TI  - Commentary: the pedunculopontine nucleus: clinical experience, basic questions
      and future directions.
AB  - This issue is dedicated to a potential new target for the treatment of movement
      disorders, the pedunculopontine tegmental nucleus (PPTg), or, more simply, the
      pedunculopontine nucleus, that some authors abbreviate as PPN. We provide an
      overview of the field as an introduction to the general reader, beginning with
      the clinical experience to date of Mazzone and co-workers in Rome, some basic
      questions that need to be addressed, and potential future directions required in
      order to ensure that the potential benefits of this work are realized.

PMID- 21188438
TI  - Redox state and energetic equilibrium determine the magnitude of stress in
      Hydrilla verticillata upon exposure to arsenate.
AB  - Arsenic (As) is a potential hazard to plants' health, however the mechanisms of
      its toxicity are yet to be properly understood. To determine the impact of redox
      state and energetic in stress imposition, plants of Hydrilla verticillata (L.f.)
      Royle, which are known to be potential accumulator of As, were exposed to 100 and
      500 MUM arsenate (AsV) for 4 to 96 h. Plants demonstrated significant As
      accumulation with the maximum being at 500 MUM after 96 h (568 MUg g(-1) dry
      weight, dw). The accumulation of As led to a significant increase in the level of
      reactive oxygen species, nitric oxide, carbonyl, malondialdehyde, and percentage
      of DNA degradation. In addition, the activity of pro-oxidant enzymes like NADPH
      oxidase and ascorbate oxidase also showed significant increases. These parameters
      collectively indicated oxidative stress, which in turn caused an increase in
      percentage of cell death. These negative effects were seemingly linked to an
      altered energetic and redox equilibrium [analyzed in terms of ATP/ADP, NADH/NAD,
      NADPH/NADP, reduced glutathione/oxidized glutathione, and
      ascorbate/dehydroascobate ratios]. Although there was significant increase in the
      levels of phytochelatins, the As chelating ligands, a large amount of As was
      presumably present as free ion particularly at 500 MUM AsV, which supposedly
      produced toxic responses. In conclusion, the study demonstrated that the
      magnitude of disturbance to redox and energetic equilibrium of plants upon AsV
      exposure determines the extent of toxicity to plants.

PMID- 21188439
TI  - Open-label study comparing the efficacy and tolerability of aripiprazole and
      haloperidol in the treatment of pediatric tic disorders.
AB  - Due to its unique pharmacodynamic properties of dopamine partial agonist
      activity, and its association with few and mild side effects, aripiprazole is a
      candidate atypical antipsychotic for patients with tic disorders. This open-label
      study compared the efficacy and tolerability of aripiprazole with haloperidol, a
      typical antipsychotic widely used to treat patients with tic disorders. Forty
      eight children and adolescents with tic disorders were recruited from the
      outpatient clinic at South Korea and treated with aripiprazole (initial dose, 5.0
      mg/d; maximum dose 20 mg/d) or haloperidol (initial dose, 0.75 mg/d; maximum
      dose, 4.5 mg/d) for 8 weeks. Treatment efficacy was measured using the yale
      global tic severity scale (YGTSS), and tolerability was measured using the
      extrapyramidal symptom rating scale (ESRS) and an adverse effects checklist.
      Total tic scores as measured by the YGTSS decreased over time in both groups (p <
      0.001) without any significant differences between groups. ESRS scores were
      significantly higher in the haloperidol group during the 4 weeks after
      commencement of medication (p < 0.05). These results indicate that aripiprazole
      may be a promising drug in the treatment of children and adolescents with tic
      disorders. Further controlled studies are needed to determine the efficacy and
      tolerability of aripiprazole in these patients.

PMID- 21188440
TI  - Preemptive analgesia with midazolam and diclofenac for hernia repair pain.
AB  - PURPOSE: The aim of this study was to compare the preemptive effects of systemic
      midazolam and diclofenac on postoperative analgesia when used before surgical
      incision. METHODS: Ninety patients, aged 35-65 years, scheduled for hernia repair
      surgery were included in the study. Forty five patients in the midazolam group
      (group M + D) received 0.05 mg/kg midazolam and 1.5 mg/kg diclofenac, 15 min
      before surgical incision; 45 patients in the diclofenac group (group D) received
      diclofenac without midazolam, 15 min before surgical incision. Postoperative pain
      (Verbal Rating Scale-6) score and first analgesic requirement were noted.
      Sedation levels were evaluated with Observer's Assessment of Alertness/Sedation
      (OAA/S) score. Adverse effects during and after the operation were also recorded.
      RESULTS: Group M + D had a significantly lower proportion of patients who
      exhibited postoperative pain than group D (11.1% vs. 37.7%, respectively; P <
      0.05). The VRS-6 score in group M + D was 1.4 (range 0-4), whereas the
      corresponding score in group D was 2.4 (range 1-6). Mean (OAA/S) score in group M
      + D was lower than in the group D (1.5 +/- 0.3 vs. 3.3 +/- 0.4, respectively; P <
      0.05). Duration of sedation in group M + D was significantly longer than the
      corresponding mean for group D (22.5 +/- 6.4 vs. 12.1 +/- 3.3 min, respectively;
      P < 0.01). The first postoperative analgesic request after surgery was 120 min in
      group M + D and 60 min in group D (P < 0.05). CONCLUSION: Midazolam enhances the
      postoperative analgesic effects of diclofenac when used before the onset of
      noxious stimuli.

PMID- 21188441
TI  - Parastomal hernia: clinical and radiological definitions.
AB  - INTRODUCTION: Parastomal hernia is a frequent complication after stoma formation.
      No consistent definition of parastomal hernia has been used in previous studies
      using clinical examination or computed tomography (CT) scan. The correlation
      between herniation rates found with clinical examination and CT scan has been
      poor. A definition of parastomal hernia with clinical examination that correlates
      with findings from CT scan should be sought. METHODS: Parastomal hernia, was with
      surgeons' clinical examination, defined as any protrusion in the vicinity of the
      stoma with the patient straining in a supine and an erect position. A new CT scan
      method was developed with the patient examined in the prone position.
      Radiologists defined herniation as any intra-abdominal content protruding beyond
      the peritoneum or the presence of a hernia sac. The correlation between
      investigators and methods were estimated by calculating Fleiss' Kappa values.
      RESULTS: Twenty-seven patients were assessed by three surgeons and three
      radiologists. For the surgeons, the Kappa value was 0.85. For the radiologists,
      it was 0.85 with CT scan in the prone position and 0.82 in the supine position.
      For the surgeons and radiologists collectively, the Kappa value was 0.80 for CT
      scan in the prone position and 0.63 in the supine position. CONCLUSION: With the
      new CT scan method examining patients in the prone position, the clinical and
      radiological definitions were highly reproducible and correlated strongly between
      methods and raters. With the strong correlation between clinical and radiological
      assessments, clinical examination alone is sufficient as follow-up. Conventional
      CT scan with the patient supine is not a reliable tool for diagnosing parastomal
      hernia.

PMID- 21188442
TI  - Not all biologics are equal!
AB  - BACKGROUND: Although the efficacy of various biologic meshes in the abdominal
      reconstruction of complex ventral hernia has been shown, the performance profile
      of various biologic mesh scaffolds in terms of hernia-specific outcomes such as
      recurrence, mesh explantation, and mesh infections has not been examined. AIM: To
      evaluate the clinical outcomes of patients who underwent complex ventral hernia
      repair with bioprosthetic material. METHODS: This study is a retrospective
      analysis of the use of bioprosthetic material in complex ventral hernia at an
      academic institution from January 2002 to December 2007. RESULTS: A total of 58
      patients with a mean age of 57.2 years and mean body mass index (BMI) of 33.8 who
      underwent reconstruction of ventral abdominal defects with a bioprosthetic from
      January 2002 to February 2009 were included in the study. The study patients had
      about 4.8 previous surgeries and 43.1% of patients had reconstruction in a
      setting of enterocutaneous fistula, while 46.6% had a previous mesh infection.
      Complex ventral hernia was seen in 50 patients, while eight patients had ventral
      and parastomal hernia. The type of biologic used for reconstruction was human
      derived (AlloDerm, 29), porcine cross-linked (CollaMend, 3; Permacol, 2), and non
      cross-linked porcine (Surgisis, 16; Strattice, 8). At least one complication was
      seen in 72.4% of patients. Major complications noted were surgical wound
      infections (19.0%), seroma (8.6%), and abscess formation (5.2%). The one-year
      hernia recurrence rate was 27.9% and mesh explantation was needed in 17.2% of
      patients. AlloDerm was less likely to be explanted (13.8%) or become infected
      (37.9%) but more likely to recur (28.6%) compared to porcine cross-linked
      bioprosthesis. Porcine cross-linked biologics were more likely to become infected
      (60%) and explanted (40%) but less likely to recur (20%) compared to AlloDerm.
      Non-cross-linked porcine biologics were less likely to be explanted (16.7%) but
      had higher recurrence (29.4%) compared to cross-linked porcine biologics and a
      higher infection rate (54.2%) compared to AlloDerm. CONCLUSIONS: The results from
      this study underscore the difficulty of repairing complex abdominal wall defects
      in contaminated fields. Cross-linked porcine biologics showed relatively higher
      infection and explantation rates. Equivalent recurrence and explantation rates
      were observed for the non-cross-linked porcine biologics and AlloDerm. These data
      indicate that there is currently no ideal biologic for complex ventral hernia
      repair.

PMID- 21188443
TI  - A magnetic fluid seal for rotary blood pumps: effects of seal structure on long
      term performance in liquid.
AB  - A magnetic fluid (MF) seal enables mechanical contact-free rotation of the shaft
      and hence has excellent durability. The performance of an MF seal, however, has
      been reported to decrease in liquids. We developed an MF seal that has a "shield"
      mechanism, and a new MF with a higher magnetization of 47.9 kA/m. The sealing
      performance of the MF seal installed in a rotary blood pump was studied. Three
      types of MF seals were used. Seal A was a conventional seal without a shield.
      Seal B had the same structure as that of Seal A, but the seal was installed at 1
      mm below liquid level. Seal C was a seal with a shield and the MF was set at 1 mm
      below liquid level. Seal A failed after 6 and 11 days. Seal B showed better
      results (20 and 73 days). Seal C showed long-term durability (217 and 275 days).
      The reason for different results in different seal structures was considered to
      be different flow conditions near the magnetic fluid. Fluid dynamics near the MF
      in the pump were analyzed using computational fluid dynamics (CFD) software. We
      have developed an MF seal with a shield that works in liquid for >275 days. The
      MF seal is promising as a shaft seal for rotary blood pumps.

PMID- 21188444
TI  - Use of DuraHeart(r) support for more than 1 year as the first successful bridge
      to heart transplantation in Japan.
AB  - We report the first successful case in Japan of use of a DuraHeart((r)) for 437
      days as a bridge to heart transplantation. A 55-year-old woman developed dilated
      cardiomyopathy at the age of 47. Her heart condition gradually deteriorated, and
      she became dependent on catecholamine support, therefore a DuraHeart((r)) was
      implanted. She had an uncomplicated postoperative course, and was discharged on
      postoperative day (POD) 54. Only once, the alarm of the controller of the
      DuraHeart((r)) gave a problem, and had to be replaced. She had no adverse events
      while she awaited heart transplantation as an outpatient. She underwent heart
      transplantation on POD 437. Strong adhesion of the drive line to the liver and
      peritoneal membrane made resection difficult. No thrombus formation was found
      inside the DuraHeart((r)), but a wedge thrombus was observed around the inflow
      cannula in the left ventricle. She was discharged on POD 38 after the
      transplantation.

PMID- 21188445
TI  - A case of isoniazid-induced liver injury diagnosed by use of the DLST, and
      successful reintroduction of isoniazid for pleural tuberculosis.
AB  - A 54-year-old woman was admitted for pleural tuberculosis diagnosed by right
      chest pain and cough. She received combination antituberculosis therapy
      consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide. However, liver
      damage was observed 15 days after initiation of therapy (aspartate
      aminotransferase (AST) 248 IU/l, alanine transaminase (ALT), 132 IU/l). The
      patient was given glycyrrhizinate intravenously, but liver damage gradually
      increased (AST 628 IU/l, ALT 467 IU/l) and all tuberculosis drugs were ceased. We
      diagnosed drug-induced liver damage due to isoniazid according to results of the
      drug lymphocyte stimulation test. We successfully reintroduced rifampicin and
      streptomycin, and carried out desensitization therapy for isoniazid without liver
      injury recurrence. Reintroduction of a drug suspected to cause drug-induced liver
      injury is generally not recommended; however, our experience suggests that
      isoniazid, a first-line antituberculosis drug, may be reintroduced after
      desensitization.

PMID- 21188446
TI  - Anti-polyribosylribitol phosphate antibody in pediatric patients with Haemophilus
      influenzae type b invasive disease.
AB  - Haemophilus influenzae type b conjugate vaccine was recently introduced to Japan
      for voluntary immunizations. H. influenzae type b remains a leading cause of
      pediatric invasive diseases in Japan. The purposes of this study were to verify
      the suitability of the H. influenzae type b conjugate vaccine for immunizing
      children with a history of invasive H. influenzae type b disease and to determine
      whether H. influenzae type b conjugate vaccine is immunogenic in these children.
      The subjects comprised 64 children with a history of invasive H. influenzae type
      b disease. Serum samples from 64 patients with H. influenzae type b systemic
      infection in the acute and convalescent phases were analyzed. Serum anti
      polyribosylribitol phosphate antibody responses of patients < 2 years old were
      poorer than those observed in patients >= 2 years old. Nineteen of the 64
      patients received a single dose of H. influenzae serotype b conjugate vaccine,
      and then follow-up serum was taken and analyzed. Eighteen of 19 patients had >= 1
      MUg/mL of anti-polyribosylribitol phosphate antibody titer after the first dose
      of H. influenzae type b conjugate vaccine. H. influenzae type b conjugate vaccine
      is immunogenic in children with invasive H. influenzae type b disease. Children <
      4 years old, and particularly < 2 years old, with invasive H. influenzae type b
      disease should receive subsequent immunization with a H. influenzae type b
      conjugate vaccine.

PMID- 21188447
TI  - Two subtypes of Churg-Strauss syndrome with neuropathy: the roles of eosinophils
      and ANCA.
AB  - The aim of this study was to clarify the differences in the pathogenesis of
      neuropathy between myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)
      positive and -negative patients with Churg-Strauss syndrome (CSS). Eight MPO-ANCA
      positive and 14 MPO-ANCA-negative patients were included. In addition to the
      standard histology, nerve biopsies were examined, employing immunohistochemistry
      for eosinophil major basic protein and electron microscopy. The groups did not
      differ significantly in clinical profiles, including the peak disability score
      and number of blood eosinophils. In nerve biopsies, necrotizing vasculitis was
      found in 63% (5/8) of the ANCA-positive and 21% (3/14) of the ANCA-negative
      patients. Fibrinoid necrosis of vessel walls was noted in 4 ANCA-positive
      patients (50%), and in one ANCA-negative patient (p = 0039). In contrast, a large
      number of eosinophilic infiltrations in the epineurium was shown in 36% (5/14) of
      the ANCA-negative patients, with no eosinophilic infiltrations shown in ANCA
      positive patients. In 3 ANCA-negative patients, endoneurial eosinophils were seen
      where focal axonal loss and capillary dilatation were occasionally noted. There
      may be 2 pathogenetic mechanisms of neuropathy with CSS: ANCA-related vascular
      fibrinoid necrosis, and a toxic eosinophilic effect on nerve fibers which is
      independent of ANCA. Therapy targeting activated eosinophils may be a possible
      treatment for intractable neuropathy of CSS.

PMID- 21188448
TI  - Efficacy and safety of tacrolimus for induction therapy in patients with active
      lupus nephritis.
AB  - After the completion of a double-blind placebo-controlled trial, tacrolimus (TAC)
      was approved for the treatment of lupus nephritis (LN) in Japan. However, the
      approved maximal dose, 3 mg/day, is almost half the dose used for induction
      therapy outside Japan. In this study, we retrospectively evaluated the efficacy
      and safety of low-dose TAC (<=3 mg/day) for induction therapy in 13 adult
      patients (2 men and 11 women) with active LN. Eight patients were treated for LN
      flares. Twelve patients underwent renal biopsies: 8 with class IV, 2 with class
      III + V, 1 with class IV + V, and 1 with class V renal histology, according to
      the International Society of Nephrology/Renal Pathology Society (ISN/RPS)
      classification. The mean initial doses of prednisone and TAC were 34.6 +/- 14.5
      and 2.7 +/- 0.6 mg/day, respectively. All the patients achieved a complete
      remission (CR) at 7.7 +/- 6.7 months (mean +/- SD) after the last administration
      of TAC, except for 2 patients who discontinued TAC treatment; 1 because of
      worsening systemic lupus erythematosus and 1 because of hypertension. Two
      patients experienced a flare-up after achieving CR. The mean blood TAC
      concentration 12 h after the last administration (C12) was significantly lower
      among the patients with flare-ups than among those with a sustained CR (1.5 +/-
      1.5 vs. 5.1 +/- 1.9 ng/mL, P = 0.034). These data showed that low-dose TAC was
      effective for induction therapy in patients with active LN, although a lower TAC
      concentration may be associated with a poor outcome.

PMID- 21188449
TI  - Comparative suppressive effects of tyrosine kinase inhibitors imatinib and
      nilotinib in models of autoimmune arthritis.
AB  - Imatinib and nilotinib are inhibitors that selectively target a set of protein
      tyrosine kinases, including abelson kinase (Abl), together with the chimeric
      oncoprotein, breakpoint cluster region-abelson kinase (Bcr-Abl), as well as stem
      cell factor receptor (KIT), platelet-derived growth factor receptor (PDGFR),
      discoidin domain receptor (DDR), and colony stimulating factor-1 receptor (CSF
      1R). The aim of the present study was to investigate whether imatinib or
      nilotinib was effective against arthritis in the glucose-6-phosphate isomerase
      (GPI)-induced arthritis mouse model. Imatinib or nilotinib was administered
      orally to the arthritic mice at different time points. Efficacy was evaluated by
      visual scoring and by determining the production of anti-GPI antibody.
      Splenocytes from the arthritic mice were cultured with GPI in the presence of
      imatinib or nilotinib in vitro, and cytokine levels in the culture supernatants
      were analyzed. To investigate the effects of imatinib and nilotinib on T-cell
      proliferation, lymph node cells from the arthritic mice were cultured with GPI in
      the presence of imatinib or nilotinib in vitro. Interleukin (IL)-17 mRNA
      expression in the arthritic ankle joints from the onset of arthritis was analyzed
      by real-time polymerase chain reaction (PCR). The administration of imatinib from
      day 0 showed suppression of arthritis (P < 0.05), the administration of nilotinib
      from day 0 resulted in pronounced suppression of arthritis (P < 0.01), and that
      from day 7 showed significant inhibition of the progression of arthritis (P <
      0.05). A reduction in anti-GPI antibodies was correlated with the therapeutic
      efficacy of imatinib, but not with that of nilotinib. Imatinib dose-dependently
      inhibited tumor necrosis factor (TNF)-alpha, IL-6, interferon (IFN)-gamma, and IL
      17 production by splenocytes in vitro, while nilotinib inhibited only IL-17 and
      IFN-gamma production in a dose-dependent fashion. Imatinib at 3 MUM exerted a
      mild antiproliferative effect on CD4+ T cells (P < 0.05), whereas imatinib at 10
      MUM and nilotinib at 3 and 10 MUM demonstrated a marked antiproliferative effect
      (P < 0.01). The IL17 gene expression level on day 7 tended to be higher than that
      on day 14. These findings suggest that imatinib and nilotinib could prevent
      autoimmune arthritis, essentially via distinct mechanisms, in that imatinib
      inhibits both inflammatory and T-cell-derived cytokine production, whereas
      nilotinib suppresses T-cell-derived cytokine production. Imatinib and nilotinib
      could have therapeutic potential for rheumatoid arthritis (RA) and other
      inflammatory diseases.

PMID- 21188450
TI  - Staphylococcal scalded skin syndrome after intra-articular injection of
      hyaluronic acid.
AB  - One of the severe adverse effects of intra-articular injection in the knee is
      septic arthritis of the knee joint. Staphylococcus aureus is the most frequent
      pathogen of septic arthritis. Staphylococcal scalded skin syndrome (SSSS) refers
      to a spectrum of blistering skin diseases caused by S. aureus exfoliative toxins.
      Although SSSS is rarely observed in adults, the mortality rate is high in adult
      cases. We report a case of SSSS due to septic knee arthritis after intra
      articular hyaluronic acid injections.

PMID- 21188451
TI  - Disseminated cutaneous and visceral Kaposi's sarcoma in a patient with rheumatoid
      arthritis receiving corticosteroids and tacrolimus.
AB  - Kaposi's sarcoma (KS) is a vascular lesion of low-grade malignant potential
      caused by the complex interactions between geographic, genetic, environmental,
      and immunological factors. We recently experienced a rare case of KS associated
      with rheumatoid arthritis in a patient receiving corticosteroids and tacrolimus;
      the KS demonstrated unusually aggressive clinical behavior. We herein report the
      details of the clinical course and discuss the possible contribution of
      corticosteroids and tacrolimus to the development of aggressive KS in the present
      case.

PMID- 21188452
TI  - Therapeutic effect of D1-like dopamine receptor antagonist on collagen-induced
      arthritis of mice.
AB  - Dopamine activates D1-like and D2-like receptors (D1R and D2R). While D1R
      antagonists have ameliorated the severity of disease in some experimental
      autoimmune models of mice by promoting interferon (IFN)-gamma and inhibiting
      interleukin (IL)-17 production by T cells, dopamine effects in the immune system
      are reportedly diverse. To investigate the impact of D1R blockade on an animal
      model of rheumatoid arthritis (RA), DBA/1 mice with collagen-induced arthritis
      (CIA) were treated with a selective D1R antagonist, SCH23390, after the primary
      immunization. This treatment suppressed the severity of the CIA. Nevertheless,
      serum levels of antibodies to type II collagen were not affected by the
      treatment. Th1/Th17 differentiation of splenic T cells in the treated animals was
      not biased. In vitro, when bone marrow-derived macrophages were stimulated in the
      presence of the D1R antagonist SCH23390, alteration of inflammatory cytokine
      expression was not observed, but their in vitro differentiation to osteoclasts
      was inhibited. Co-administration of a selective D1R agonist, A68930, abrogated
      the in vivo anti-arthritic effect and the in vitro suppression of
      osteoclastogenesis by the D1R antagonist. Our results argue that D1R blockade is
      potentially a new approach to the treatment of RA. Its effect could be partly
      attributable to the inhibition of osteoclastogenesis.

PMID- 21188453
TI  - A multicentre trial of bucillamine in the treatment of early rheumatoid arthritis
      (SNOW study).
AB  - In this study, we enrolled early rheumatoid arthritis (RA) patients at multiple
      institutes who fulfilled the American Rheumatism Association 1987 revised
      criteria for the classification of RA, and followed the clinical results of
      disease-modifying anti-rheumatic drug (DMARD) treatment prospectively. With the
      aim of developing therapeutic guidelines using the disease activity score 28
      (DAS28) as disease indices, we investigated the usefulness of bucillamine (BUC),
      one of the most widely used DMARDs in Japan. Eighty-one patients with early RA
      who had not previously been treated with DMARDs were suitable for BUC therapy as
      first-choice treatment. After 24 months of treatment, at least moderate
      improvement was seen in 87.5% of patients using the DAS28 erythrocyte
      sedimentation rate (ESR). After 24 months of BUC therapy, 7 patients (43.8%) met
      the remission criterion of DAS28 (ESR) <2.6. The 24-month BUC continuation rate
      was 60.5% (49/81, monotherapy + combination therapy), of which 59.2% (29/49) were
      on BUC monotherapy. From the efficacy and safety viewpoints alike, BUC was useful
      as first-choice treatment for early RA.

PMID- 21188454
TI  - Reduction in serum levels of substance P in patients with rheumatoid arthritis by
      etanercept, a tumor necrosis factor inhibitor.
AB  - We determined the effects of etanercept on the serum concentrations of
      neuropeptides in RA patients. In a total of 11 patients who had been injected
      with etanercept, the serum levels of substance P, calcitonin gene-related peptide
      (CGRP), and gastrin-releasing peptide (GRP) were analyzed. Average levels of
      serum substance P were significantly reduced from 1.53 to 0.62 ng/ml after the
      injection of etanercept. In the CGRP and GRP analyses, these average levels
      dropped from 1.57 and 0.51 ng/ml to 0.44 and 0.04 ng/ml, respectively. Etanercept
      appears to decrease substance P levels with an improvement in disease activities.

PMID- 21188456
TI  - The sick building syndrome as a part of the autoimmune (auto-inflammatory)
      syndrome induced by adjuvants.
AB  - Sick building syndrome (SBS) is a term coined for a set of clinically
      recognizable symptoms and ailments without a clear cause reported by occupants of
      a building. In the 1990s the term "functional somatic syndromes" was applied to
      several syndromes, including SBS, multiple chemical sensitivity, repetition
      stress injury, the side effects of silicone breast implants, the Gulf War
      syndrome (GWS), chronic fatigue syndrome, the irritable bowel syndrome, and
      fibromyalgia. Recently, Shoenfeld and Agmon-Levin suggested that four conditions-
      siliconosis, macrophagic myofascitis, the GWS, and post-vaccination phenomena-
      which share clinical and pathogenic resemblances, may be included under a common
      syndrome entitled the "autoimmune (auto-inflammatory) syndrome induced by
      adjuvants". Comparison of the clinical manifestations, symptoms, and signs of the
      four conditions described by Shoenfeld and Agmon-Levin with those described for
      SBS shows that nine out of ten main symptoms are present in all 5 conditions.
      Shoenfeld and Agmon-Levin further propose several major and minor criteria,
      which, although requiring further validation, may aid in the diagnosis of this
      newly defined syndrome. We propose here that SBS may also be included as a part
      of "Shoenfeld's syndrome".

PMID- 21188455
TI  - Concurrent presentation of cryptococcal meningoencephalitis and systemic lupus
      erythematosus.
AB  - Cryptococcal meningitis is a recognized complication of systemic lupus
      erythematosus (SLE), with high mortality rates, particularly in those treated
      with immunosuppressive agents. We describe a patient diagnosed simultaneously
      with cryptococcal meningoencephalitis and SLE and reviewed four similar cases
      reported in the literature. In our case, profound low CD4 lymphocyte count and
      low complement levels were observed. The patient was treated with prednisolone,
      fluconazole, and 5-flucytosine and evinced good clinical improvement. This case
      suggests that intrinsic immunological abnormality related to SLE predisposed to
      opportunistic infections.

PMID- 21188457
TI  - Estimation of outcrossing rates at small-scale flowering sites of the dwarf
      bamboo species, Sasa cernua.
AB  - We estimated the outcrossing rates at small-scale flowering sites of an endemic
      dwarf bamboo species, Sasa cernua. The multi-locus estimation of the outcrossing
      rate of the dwarf bamboo population was 0.148 (SD 0.118). Two culms with the
      highest outcrossing rates had heterozygous genotypes at one locus, but other
      culms in the locus were homozygotes. Five culms with high outcrossing rates bore
      2-17% seeds with homozygous genotypes. Due to predominant selfing, the overall
      inbreeding coefficient of seeds was high, although it declined in seedlings. This
      suggests that selection against inbred progenies began early in the establishment
      process in the natural habitat.

PMID- 21188458
TI  - Physiological characterization of the Arabidopsis thaliana oxidation-related zinc
      finger 1, a plasma membrane protein involved in oxidative stress.
AB  - The CCCH-type zinc finger proteins are a superfamily containing tandem zinc
      binding motifs involved in many aspects of plant growth and development. However,
      the precise role of these proteins involved in plant stress tolerance is poorly
      understood. This study was to examine the regulatory and functional role of the
      CCCH-type zinc finger protein, AtOZF1 (At2g19810), under oxidative stress.
      Interestingly, the AtOZF1 protein was localized in the plasma membrane. The
      AtOZF1 transcripts were highly induced by treatment with hydrogen peroxide,
      abscisic acid and salinity. The AtOZF1-overexpressing plants were relatively
      resistant to oxidative stress than wild-type and T-DNA insertion mutant atozf1.
      Malondialdehyde, a decomposition product of lipid peroxidation, accumulated in
      atozf1 mutants more than in wild-type and AtOZF1-overexpressing plants.
      Furthermore, atozf1 mutants displayed lower activities of catalase and guaiacol
      peroxidase, higher chlorosis, and down-regulated expression of antioxidant genes
      under oxidative stress. Taken together, these observations demonstrate that
      AtOZF1 is required for the tolerance of Arabidopsis to oxidative stress.

PMID- 21188459
TI  - Rate accelerations in nuclear 18S rDNA of mycoheterotrophic and parasitic
      angiosperms.
AB  - Rate variation in genes from all three genomes has been observed frequently in
      plant lineages with a parasitic and mycoheterotrophic mode of life. While the
      loss of photosynthetic ability leads to a relaxation of evolutionary constraints
      in genes involved in the photosynthetic apparatus, it remains to be determined
      how prevalent increased substitution rates are in nuclear DNA of non
      photosynthetic angiosperms. In this study we infer rates of molecular evolution
      of 18S rDNA of all parasitic and mycoheterotorphic plant families (except
      Lauraceae and Polygalaceae) using relative rate tests. In several holoparasitic
      and mycoheterotrophic plant lineages extremely high substitution rates are
      observed compared to other photosynthetic angiosperms. The position and frequency
      of these substitutions have been identified to understand the mutation dynamics
      of 18S rRNA in achlorophyllous plants. Despite the presence of significantly
      elevated substitution rates, very few mutations occur in major functional and
      structural regions of the small ribosomal molecule, providing evidence that the
      efficiency of the translational apparatus in non-photosynthetic plants has not
      been affected.

PMID- 21188460
TI  - Orthostatic heart rate responses after prolonged space flights.
AB  - Orthostatic tachycardia (POTS) can occur after space flights. We determined
      orthostatic heart rate responses in 18 cosmonauts before and 3-5 days after long
      term space missions. Cosmonauts undergoing a cardiovascular training program in
      space experienced only moderate POTS after their return to earth. Cardiovascular
      countermeasures may have attenuated POTS. Another possible interpretation is that
      cardiovascular deconditioning is not sufficient to elicit full blown POTS in the
      absence of additional genetic or environmental factors.

PMID- 21188461
TI  - Novel macrophage polarization model: from gene expression to identification of
      new anti-inflammatory molecules.
AB  - Plasticity is a well-known property of macrophages that is controlled by
      different changes in environmental signals. Macrophage polarization is regarded
      as a spectrum of activation phenotypes adjusted from one activation extreme, the
      classic (M1), to the other, the alternative (M2) activation. Here we show, in
      vitro and in vivo, that both M1 and M2 macrophage phenotypes are tightly coupled
      to specific patterns of gene expression. Novel M2-associated markers were
      characterized and identified as genes controlling the extracellular metabolism of
      ATP to generate pyrophosphates (PPi). Stimulation of M1 macrophages with PPi
      dampens both NLR and TLR signaling and thus mediates cytokine production. In this
      context extracellular PPi enhanced the resolution phase of a murine peritonitis
      model via a decrease in pro-inflammatory cytokine production. Therefore, our
      study reveals an additional level of plasticity modulating the resolution of
      inflammation.

PMID- 21188462
TI  - Molecular enigma of multicolor bioluminescence of firefly luciferase.
AB  - Firefly luciferase-catalyzed reaction proceeds via the initial formation of an
      enzyme-bound luciferyl adenylate intermediate. The chemical origin of the color
      modulation in firefly bioluminescence has not been understood until recently. The
      presence of the same luciferin molecule, in combination with various mutated
      forms of luciferase, can emit light at slightly different wavelengths, ranging
      from red to yellow to green. A historical perspective of development in
      understanding of color emission mechanism is presented. To explain the variation
      in the color of the bioluminescence, different factors have been discussed and
      five hypotheses proposed for firefly bioluminescence color. On the basis of
      recent results, light-color modulation mechanism of firefly luciferase propose
      that the light emitter is the excited singlet state of OL(-) [(1)(OL(-))*], and
      light emission from (1)(OL(-))* is modulated by the polarity of the active-site
      environment at the phenol/phenolate terminal of the benzothiazole fragment in
      oxyluciferin.

PMID- 21188463
TI  - Biased binding of class IA phosphatidyl inositol 3-kinase subunits to inducible
      costimulator (CD278).
AB  - To better understand T lymphocyte costimulation by inducible costimulator (ICOS;
      H4; CD278), we analyzed proteins binding to ICOS peptides phosphorylated at the
      Y(191)MFM motif. Phosphorylated ICOS binds class IA phosphatidyl inositol 3
      kinase (PI3-K) p85alpha, p50-55alpha and p85beta regulatory subunits and
      p110alpha, p110delta and p110beta catalytic subunits. Intriguingly, T cells
      expressed high levels of both p110alpha or p110delta catalytic subunits, yet ICOS
      peptides, cell surface ICOS or PI3-kinase class IA regulatory subunits
      preferentially coprecipitated p110alpha catalytic subunits. Silencing p110alpha
      or p110delta partially inhibited Akt/PKB activation induced by anti-CD3 plus anti
      ICOS antibodies. However, silencing p110alpha enhanced and silencing p110delta
      inhibited Erk activation. Both p110alpha- and p110delta-specific inhibitors
      blocked cytokine secretion induced by TCR/CD3 activation with or without ICOS
      costimulus, but only p110alpha inhibitors blocked ICOS-induced cell elongation.
      Thus, p110alpha and p110delta are essential to optimal T cell activation, but
      their abundance and activity differentially tune up distinct ICOS signaling
      pathways.

PMID- 21188465
TI  - Everolimus-related organizing pneumonia: a report establishing causality.

PMID- 21188464
TI  - A Phase Ib pharmacokinetic study of the anti-angiogenic agent CKD-732 used in
      combination with capecitabine and oxaliplatin (XELOX) in metastatic colorectal
      cancer patients who progressed on irinotecan-based chemotherapy.
AB  - BACKGROUND: We conducted a Phase I clinical trial to evaluate the safety,
      tolerability, and pharmacokinetics (PK) of CKD-732 [6-O-(4-dimethylaminoethoxy)
      cinnamoyl fumagillol hemioxalate] in combination with capecitabine and
      oxaliplatin (XELOX) in nine metastatic colorectal cancer patients who had
      progressed on irinotecan-based chemotherapy. METHODS: Using a dose-escalation
      schedule, CKD-732 doses of 2, 5, or 10 mg/m(2)/d were administered twice weekly
      for 2 weeks, followed by a 1-week rest. Oxaliplatin (130 mg/m(2)) was
      administered on day 1, and capecitabine (1,000 mg/m(2) twice a day) was orally
      administered for 14 days of a 3-week cycle. RESULTS: In the group given the 10
      mg/m(2)/d dose, two patients experienced dose limiting toxicities (one had grade
      3 nausea, insomnia, and fatigue; the other had grade 3 insomnia). The maximum
      tolerated dose was 10 mg/m(2)/d, and the clinically recommended dose was 5
      mg/m(2)/d for CKD-732 in combination with XELOX. Frequently encountered non
      hematological grade 3/4 adverse events included insomnia (22.2%), fatigue
      (11.1%), sensory neuropathy (11.1%), hyperbilirubinemia (11.1%), and dyspnea
      (11.1%). The area under the concentration-time curve and maximum concentration of
      CKD-732 increased in a dose-dependent manner. There were no notable effects of
      CKD-732 on the PK of capecitabine and oxaliplatin-derived platinum. CONCLUSION:
      The Phase II recommended dose of CKD-732 was determined to be 5 mg/m(2)/d, and
      this dose was safely combined with a conventional dose of capecitabine and
      oxaliplatin in this patient population. Further studies on the effects of CKD-732
      in combination with XELOX and other chemotherapies using a larger study
      population are warranted.

PMID- 21188466
TI  - Effect of hepatic or renal impairment on the pharmacokinetics of casopitant, a NK
      1 receptor antagonist.
AB  - Two studies were conducted in subjects with mild or moderate hepatic or renal
      impairment and subjects with normal organ function to evaluate the
      pharmacokinetics of casopitant and to assess its safety in these populations. A
      total of 26 subjects were enrolled in the hepatic impairment study and 18
      subjects in the renal impairment study. All subjects received oral casopitant 100
      mg once-daily for 5 days. Casopitant area under the concentration-time curve
      (AUC) increased 11% and 24% in subjects with mild or moderate hepatic impairment,
      respectively, on Day 1, compared with subjects with normal hepatic function; a
      similar increase was observed on Day 5. The AUC of the active major metabolite,
      GSK525060, was reduced 29% and 19% on Days 1 and 5, respectively, in subjects
      with moderate hepatic impairment, but not altered by mild hepatic impairment.
      Casopitant AUC increased 34% and 22% on Day 1 in subjects with mild or moderate
      renal impairment, respectively, and 28% and 11% on Day 5, respectively, compared
      with subjects with normal renal function. GSK525060 AUC was increased 17% and 24%
      on Days 1 and 5, respectively, in subjects with mild renal impairment; but did
      not significantly change in subjects with moderate renal impairment. Further age
      adjusted analysis showed no meaningful effect of renal impairment on casopitant
      or GSK525060 AUC. Plasma protein binding of casopitant and GSK525060 was similar
      in all subjects. The pharmacokinetics of casopitant is not altered to a
      clinically significant extent in subjects with mild or moderate, hepatic or renal
      impairment. The impact of severe hepatic or renal impairment was not evaluated.

PMID- 21188468
TI  - The role of 99mTc-tetrofosmin brain SPECT in differentiating treatment-induced
      necrosis from recurrent brain tumor.

PMID- 21188469
TI  - Glioneuronal tumor with neuropil-like islands of the spinal cord with diffuse
      leptomeningeal neuraxis dissemination.
AB  - A 54-year-old Caucasian female presented with a 1 year history of intermittent
      numbness of the left leg progressing to bilateral, lower extremity sensory loss
      that advanced to include impaired vibration and proprioception. The subsequent
      thoracic spine magnetic resonance imaging (MRI) scan revealed a heterogeneous,
      avidly enhancing, centrally situated spinal cord mass involving T7 through T10 in
      association with thick linear enhancement of the anterior and posterior cord
      surfaces extending both superiorly and inferiorly. Both the cervical and lumbar
      spine MRI demonstrated diffuse leptomeningeal disease as well. A brain MRI
      revealed focal leptomeningeal enhancement in the left and right sylvian fissures,
      the suprasellar cistern, and the posterior fossa; a pattern consistent with
      metastatic disease. The patient underwent a T6-T10 laminectomy for tumor biopsy
      and debulking. Histology revealed a WHO grade III glioneuronal tumor with
      rosetted neuropil-like islands. Synaptophysin and neurofilament (NF) positive
      staining was noted within the neural appearing component, whereas, glial
      fibrillary acidic protein (GFAP) immunopositivity was evident in the fibrillary
      astrocytoma component of the tumor. The Ki-67 labeling index was 7%. This tumor
      pattern, now included in the 2007 World Health Organization (WHO) classification
      of central nervous system tumours as a pattern variation of anaplastic
      astrocytoma (Kleihues et al. In: Louis et al. (eds) WHO classification of tumours
      of the central nervous system, 2007), was first described in a four-case series
      by Teo et al. in 1999. The majority of subsequently reported cases described them
      as primary tumors of the cerebrum. Herein, we report a unique example of a spinal
      glioneuronal tumor with neuropil-like islands with associated leptomeningeal
      dissemination involving the entire craniospinal axis.

PMID- 21188470
TI  - Measurement of psychological distress in patients with intracranial tumours: the
      NCCN distress thermometer.
AB  - Identification of patients suffering from elevated psychosocial distress, the
      sources of the distress, and the necessary treatment of the distress can be
      rather difficult within the neurosurgical setting (e.g., lack of time, cognitive
      or aphasic disorders of the patients). The distress thermometer (DT) is a single
      item rapid distress screening tool by use of which these difficulties can be
      minimized. The objective of this study was to determine the optimum DT cut-off
      score that would identify significant distress in patients with intracranial
      tumours thus validating its use in the neurosurgical setting. In all, 150
      patients were tested either during in-patient stay or during a follow-up
      examination before and after the neurosurgical removal of a primary intracranial
      neoplasm. Patients were administered the DT with the hospital anxiety and
      depression scale (HADS), the gold standard against which the DT was compared. The
      area under the receiver operating characteristics curve (ROC) was >=0.82. Thus,
      the ability of the DT to correctly identify patients as significantly distressed
      was excellent. The DT ranges from 0 to 10. Its optimum cut-off score for
      identifying distressed patients was at or above 6 (sensitivity >= 88%;
      specificity >= 53%). The DT is a valid and practicable screening instrument for
      assessment of levels and sources of distress in patients with intracranial
      tumours in the neurosurgical setting.

PMID- 21188472
TI  - Observing selected domains in multi-domain proteins via sortase-mediated ligation
      and NMR spectroscopy.
AB  - NMR spectroscopy has distinct advantages for providing insight into protein
      structures, but faces significant resolution challenges as protein size
      increases. To alleviate such resonance overlap issues, the ability to produce
      segmentally labeled proteins is beneficial. Here we show that the S. aureus
      transpeptidase sortase A can be used to catalyze the ligation of two separately
      expressed domains of the same protein, MecA (B. subtilis). The yield of purified,
      segmentally labeled MecA protein conjugate is approximately 40%. The resultant
      HSQC spectrum obtained from this domain-labeled conjugate demonstrates successful
      application of sortase A for segmental labeling of multi-domain proteins for
      solution NMR study.

PMID- 21188473
TI  - Bioethics on the subcontinent: the Sindh Institute in Karachi.
AB  - In this personal narrative the author recounts his experiences teaching bioethics
      in Pakistan. He notes the different moral, cultural and legal environments of
      Pakistan as compared to the United States, and in particular, the ways in which
      subtle interpretations of Sharia law shape bioethical reflections as well as the
      biomedical legal environment. As he argues, any attempt to export models of
      bioethics from one country to another with no attention to social and cultural
      differences is a recipe for failure. To presume that all ethical considerations
      are universal is to devalue moral traditions that differ from our own, and
      dismiss cultural values of other societies.

PMID- 21188471
TI  - PTEN restoration and PIK3CB knockdown synergistically suppress glioblastoma
      growth in vitro and in xenografts.
AB  - Glioblastoma is the most frequent and malignant glioma in adults. To develop an
      effective gene therapy strategy for glioblastoma, we investigated the anti
      proliferative effects of phosphatase and tensin homolog (PTEN) restoration and
      siRNAs specifically targeting PIK3CB and PIK3CA on PTEN-deficient glioblastoma
      cells in vitro and in subcutaneous xenografts. Restoration of PTEN or knockdown
      of PIK3CB, but not PIK3CA, in glioblastoma cells markedly down-regulates the
      phosphorylation level of AKT, inhibits cell proliferation and colony formation,
      arrests the cell cycle at the G0/G1 stage, and promotes caspase-dependent
      apoptosis. Combined treatment with PTEN restoration and PIK3CB knockdown shows
      strong synergy. PTEN restoration or PIK3CB knockdown is also able to efficiently
      inhibit the growth of human U251 glioblastoma xenografts in nude mice, while
      tumor growth is entirely suppressed by a combination of the two treatments. In
      addition, we found that the mRNA levels of inhibitors of apoptosis proteins
      (IAPs) are reduced in U251 cells by PTEN restoration, suggesting that combined
      antitumor effects may also be partly attributed to the inhibition of the IAP
      pathway by PTEN restoration. Collectively, our results demonstrate that PI3 K
      isoforms play specific roles in tumorigenesis, and that combined treatment of
      PTEN restoration and PIK3CB siRNA is a promising gene therapy strategy for PTEN
      deficient gliomas.

PMID- 21188474
TI  - Iron acquisition with the natural siderophore enantiomers pyochelin and enantio
      pyochelin in Pseudomonas species.
AB  - The bacterial siderophore pyochelin is composed of salicylate and two cysteine
      derived heterocycles, the second of which is modified by reduction and N
      methylation during biosynthesis. In Pseudomonas aeruginosa, the first cysteine
      residue is converted to its D-isoform during thiazoline ring formation, whereas
      the second cysteine remains in its L-configuration. Stereochemistry is opposite
      in the Pseudomonas fluorescens siderophore enantio-pyochelin, in which the first
      ring originates from L-cysteine and the second ring from D-cysteine. Both
      siderophores promote growth of the producer organism during iron limitation and
      induce the expression of their biosynthesis genes by activating the
      transcriptional AraC-type regulator PchR. However, neither siderophore is
      functional as an iron carrier or as a transcriptional inducer in the other
      species, demonstrating that both processes are highly stereospecific.
      Stereospecificity of pyochelin/enantio-pyochelin-mediated iron uptake is ensured
      at two levels: (i) by the outer membrane siderophore receptors and (ii) by the
      cytosolic PchR regulators.

PMID- 21188475
TI  - The ArsD As(III) metallochaperone.
AB  - Arsenic, a toxic metalloid widely existing in the environment, causes a variety
      of health problems. The ars operon encoded by Escherichia coli plasmid R773 has
      arsD and arsA genes, where ArsA is an ATPase that is the catalytic subunit of the
      ArsAB As(III) extrusion pump, and ArsD is an arsenic chaperone for ArsA. ArsD
      transfers As(III) to ArsA and increases the affinity of ArsA for As(III),
      allowing resistance to environmental concentrations of arsenic. Cys12, Cys13 and
      Cys18 in ArsD form a three sulfur-coordinated As(III) binding site that is
      essential for metallochaperone activity. ATP hydrolysis by ArsA is required for
      transfer of As(III) from ArsD to ArsA, suggesting that transfer occurs with a
      conformation of ArsA that transiently forms during the catalytic cycle. The 1.4 A
      x-ray crystal structure of ArsD shows a core of four beta-strands flanked by four
      alpha-helices in a thioredoxin fold. Docking of ArsD with ArsA was modeled in
      silico. Independently ArsD mutants exhibiting either weaker or stronger
      interaction with ArsA were selected. The locations of the mutations mapped on the
      surface of ArsD are consistent with the docking model. The results suggest that
      the interface with ArsA involves one surface of alpha1 helix and metalloid
      binding site of ArsD.

PMID- 21188477
TI  - Hydrocarbon degradation potential of salt marsh plant-microorganisms
      associations.
AB  - Estuaries are often considered sinks for contaminants and the cleanup of salt
      marshes, sensitive ecosystems with a major ecological role, should be carried out
      by means of least intrusive approaches, such as bioremediation. This study was
      designed to evaluate the influence of plant-microorganisms associations on
      petroleum hydrocarbons fate in salt marshes of a temperate estuary (Lima River,
      NW Portugal). Sediments un-colonized and colonized (rhizosediments) by different
      plants (Juncus maritimus, Phragmites australis, Triglochin striata and Spartina
      patens) were sampled in four sites of the lower and middle estuary for
      hydrocarbon degrading microorganisms (HD), total cell counts (TCC) and total
      petroleum hydrocarbons (TPHs) assessment. In general, TPHs, HD and TCC were
      significantly higher (P < 0.05) in rhizosediments than in un-colonized sediments.
      Also recorded were differences on the abundance of hydrocarbon degraders among
      the rhizosediment of the different plants collected at the same site (J.
      maritimus < P. australis < T. striata), with statistically significant
      differences (P < 0.05) between J. maritimus and T. striata. Moreover, strong
      positive correlations-0.81 and 0.84 (P < 0.05), between biotic (HD) and abiotic
      (organic matter content) parameters and TPHs concentrations were also found. Our
      data clearly suggest that salt marsh plants can influence the microbial
      community, by fostering the development of hydrocarbon-degrading microbial
      populations in its rhizosphere, an effect observed for all plants. This effect,
      combined with the plant capability to retain hydrocarbons around the roots,
      points out that salt marsh plant-microorganisms associations may actively
      contribute to hydrocarbon removal and degradation in estuarine environments.

PMID- 21188476
TI  - Biodegradation of leuco derivatives of triphenylmethane dyes by Sphingomonas sp.
      CM9.
AB  - A leuco derivatives of triphenylmethane dyes degrading bacterium, strain CM9, was
      isolated from an aquafarm field. Based on morphology, physiologic tests, 16S rDNA
      sequence, and phylogenetic characteristics, it was identified as Sphingomonas sp.
      This strain was capable of degrading leucomalachite green (LMG), leucocrystal
      violet and leucobasic fuchsin completely. The relationship between bacterium
      growth and LMG degradation suggested that strain CM9 could use LMG as the sole
      source of carbon. The most LMG degradation activity of CM9 crude extract was
      observed at pH 7.0 and at 30 degrees C. Many metal ions had little inhibition
      effect on the degradation activity of the crude extract. CM9 also showed strong
      decolorization of triphenylmethane dyes to their leuco derivatives. GC/MS
      analysis detected two novel metabolic products, methylbenzene and 4-aminophenol,
      during the LMG degradation by CM9.

PMID- 21188478
TI  - Ten-year risk of all-cause mortality: assessment of a risk prediction algorithm
      in a French general population.
AB  - While assessment of global cardiovascular risk is uniformly recommended for risk
      factor management, prediction of all-cause death has seldom been considered in
      available charts. We established an updated algorithm to predict absolute 10-year
      risk of all-cause mortality in apparently healthy subjects living in France, a
      country with high life expectancy. Analyses were based on the Third French MONICA
      Survey on cardiovascular risk factors (1995-1996) carried out in 3,208
      participants from the general population aged 35-64. Vital status was obtained 10
      years after inclusion and assessment of determinants of mortality was based on
      multivariable Cox modelling. One-hundred-fifty-six deaths were recorded.
      Independent determinants of mortality were living area (Northern France), older
      age, male gender, no high-school completion, smoking, systolic blood pressure >=
      160 mmHg, LDL-cholesterol >= 5.2 mmol/l, and diabetes. Score sheets were
      developed to easily estimate 10-year risk of death. For example, a non diabetic,
      heavy smoker, 46-year old man, living in South-Western France, who did not
      complete high-school, with LDL-cholesterol >= 5.2 mmol/l and systolic blood
      pressure < 160 mmHg, has a 17% probability of death in the ten coming years. The
      C-statistic of the prediction model was 0.76 [95% CI: 0.72-0.80] with a degree of
      overoptimism estimated at 0.0058 in a bootstrap sample. Calibration was
      satisfying: P value for Hosmer-Lemeshow chi(2) test was 0.483. This prediction
      algorithm is a simple tool for guiding practitioners towards a more or less
      aggressive management of risk factors in apparently healthy subjects.

PMID- 21188479
TI  - Risk factors for type 2 diabetes in groups stratified according to metabolic
      syndrome: a 10-year follow-up of the Tromso Study.
AB  - Many incident cases of type 2 diabetes do not fulfil the metabolic syndrome,
      which accordingly has been questioned both as a research and clinical tool. The
      aim of this study was to determine differences in risk factors for type 2
      diabetes between groups with high or low metabolic score. The study population
      were 26,093 men and women attending the Tromso Study in 1994, followed through
      2005, and who did not have diabetes when entering the study. A total of 492
      incident cases of type 2 diabetes were registered. A metabolic score was defined
      according to a modified version of the National Cholesterol Education Program
      Adult Treatment Panel III. For those fulfilling >= 3 metabolic score criteria,
      increasing age, body mass index (BMI), triglycerides and a family history of
      diabetes were independent predictors. Age, BMI, and triglycerides predicted type
      2 diabetes more strongly in subjects with low metabolic score, whereas high HDL
      cholesterol was not protective in this low risk group. The risk associated with a
      positive family history was unaffected by level of metabolic score. In addition
      smoking, low education and in men also physical inactivity were independent risk
      factors only in those with low metabolic score. Adding these non-metabolic risk
      factors increased correct classification from an ROC area of 77.2 to 87.1% (P
      value < 0.0001). One half of the incident cases of type 2 diabetes were missed by
      using high metabolic score for risk prediction.

PMID- 21188480
TI  - Estimation of the contribution of biomarkers of different metabolic pathways to
      risk of type 2 diabetes.
AB  - The contribution of different biological pathways to the development of type 2
      diabetes was quantified in a case-cohort design based on circulating blood
      biomarkers from participants aged 35-65 years in the EPIC-Potsdam Study. The
      analytic sample included 613 participants with incident diabetes and 1965
      participants without diabetes. The proportion that each biomarker contributed to
      the risk of diabetes was quantified using effect decomposition method. Summarized
      risk of each biomarker was estimated by an index based on quintiles of gamma
      glutamyltransferase (GGT), HDL-cholesterol, hs-CRP, and adiponectin. Cox
      proportional hazard regression was used to estimate relative risks adjusted for
      age, sex, body mass index, waist-circumference, education, sport activity,
      cycling, occupational activity, smoking, alcohol intake, and consumptions of red
      meat, coffee and whole grain bread. Adiponectin explained a total of 32.1% (CI =
      16.8, 49.1%) of the risk related to index. For the other biomarkers the
      corresponding proportions were 23.5% (CI = 10.1, 37.8%) by HDL-cholesterol, 21.5%
      (CI = 11.5, 32.8%) by GGT, and 15.5% (CI = 4.44, 27.3%) by hs-CRP. The results
      support the hypothesis that the different biological pathways reflected by GGT,
      HDL-cholesterol, hs-CRP and adiponectin independent from each other contribute to
      the risk of type 2 diabetes. Of these pathways the highest contribution was
      observed for adiponectin which contributed one-third to the risk and that equal
      proportion was contributed by GGT and HDL-cholesterol, although the contribution
      of inflammation was lower.

PMID- 21188481
TI  - Effect of heat treatments on apatite-forming ability of NaOH- and HCl-treated
      titanium metal.
AB  - Titanium (Ti) metal was soaked in HCl solution after NaOH treatment and then
      subjected to heat treatments at different temperatures. Their apatite-forming
      abilities in a simulated body fluid (SBF) were discussed in terms of their
      surface structures and properties. The nanometer scale roughness formed on Ti
      metal after NaOH treatment remained after the HCl treatment and a subsequent heat
      treatment below 700 degrees C. Hydrogen titanate was formed on Ti metal from an
      HCl treatment after NaOH treatment, and this was converted into titanium oxide of
      anatase and rutile phases by a subsequent heat treatment above 500 degrees C. The
      scratch resistance of the surface layer increased with the formation of the
      titanium oxide after a heat treatment up to 700 degrees C, and then decreased
      with increasing temperature. The Ti metal with a titanium oxide layer formed on
      its surface showed a high apatite-forming ability in SBF when the heat treatment
      temperature was in the range 500-700 degrees C. The high apatite-forming ability
      was attributed to the positive surface charge in an SBF. These positive surface
      charges were ascribed to the presence of chloride ions, which were adsorbed on
      the surfaces and dissociated in the SBF to give an acid environment.

PMID- 21188482
TI  - Magnetically mediated release of ciprofloxacin from polyvinyl alcohol based
      superparamagnetic nanocomposites.
AB  - Polymer nanocomposites exhibiting superparamagnetic behavior have been recognized
      as a promising tool to achieve targeted drug delivery using external magnetic
      field for treating complex diseases like cancers and tumors. The present
      investigation attempts to design a superparamagnetic nanocomposite which could
      desirably deliver ciprofloxacin drug by application of varying magnetic field. In
      order to achieve the proposed objectives, a polymer matrix of polyvinyl alcohol-g
      polymethyl methacrylate was prepared by free radical polymerization and iron
      oxide particles were impregnated by in situ precipitation method. The prepared
      nanocomposites were characterized by techniques like FTIR, electron microscopy
      (SEM and TEM) and XRD and magnetization studies were performed to ensure
      superparamagnetic behavior. The antibiotic drug ciprofloxacin was loaded onto the
      magnetic nanocomposites and the influence of various factors such as percent
      loading, chemical composition of the nanocomposite, applied magnetic field, pH of
      the release medium were investigated on the release profiles of the drug. The
      chemical integrity of the drug and its antibacterial potential were also studied.
      The dynamics of the release process was also examined mechanistically.

PMID- 21188483
TI  - An extended spectrum bactericidal titanium dioxide (TiO2) coating for metallic
      implants: in vitro effectiveness against MRSA and mechanical properties.
AB  - Implant infections remain feared and severe complications after total joint
      arthroplasty. The incidence of multi-resistant pathogens, causing such
      infections, is rising continuously, and orthopaedic surgeons are confronted with
      an ever-changing resistance pattern. Anti-infectious surface coatings aim for a
      high local effective concentration and a low systemic toxicity at the same time.
      Antibacterial efficacy and biomechanical stability of a novel broad-spectrum anti
      infectious coating is assessed in the present study. Antibacterial efficacy of a
      sol-gel derived titanium dioxide (TiO(2)) coating for metal implants with and
      without integrated copper ions as antibiotic agent was assessed against
      methicillin resistant Staphylococcus aureus (MRSA 27065). Both bacterial surface
      adhesion and growth of planktonic bacteria were assessed with bare and various
      TiO(2)-coated Ti6Al4V metal discs. Furthermore, bonding strength of the TiO(2)
      surface coating, using standard testing procedures, as well as surface roughness
      were determined. We found a significant reduction of the bacterial growth rate
      for the coatings with integrated copper ions, with highest reduction rates
      observed for a fourfold copper TiO(2)-coating. Pure TiO(2) without integrated
      copper ions did not reduce bacterial growth compared to uncoated Ti6Al4V. The
      coating was not detached from the substrate by standard adhesive failure testing,
      which indicated an excellent durability of the implant coating. The TiO(2)
      coating with integrated copper ions could offer a new strategy for preventing
      implant-associated infections, with antibacterial properties not only against the
      most common bacteria causing implant infections but also against multiresistant
      strains such as MRSA.

PMID- 21188484
TI  - Synthesis, bioactivity and preliminary biocompatibility studies of glasses in the
      system CaO-MgO-SiO2-Na2O-P2O5-CaF2.
AB  - New compositions of bioactive glasses are proposed in the CaO-MgO-SiO(2)-Na(2)O
      P(2)O(5)-CaF(2) system. Mineralization tests with immersion of the investigated
      glasses in simulated body fluid (SBF) at 37 degrees C showed that the glasses
      favour the surface formation of hydroxyapatite (HA) from the early stages of the
      experiments. In the case of daily renewable SBF, monetite (CaHPO(4)) formation
      competed with the formation of HA. The influence of structural features of the
      glasses on their mineralization (bioactivity) performance is discussed.
      Preliminary in vitro experiments with osteoblasts' cell-cultures showed that the
      glasses are biocompatible and there is no evidence of toxicity. Sintering and
      devitrification studies of glass powder compacts were also performed. Glass
      ceramics with attractive properties were obtained after heat treatment of the
      glasses at relatively low temperatures (up to 850 degrees C).

PMID- 21188485
TI  - The basketweave form of the Z-band is expanded relative to the small-square form.

PMID- 21188486
TI  - Expression and functional role of HLA-G in immune cells from patients with
      systemic lupus erythematosus.
AB  - Human leukocyte antigen (HLA)-G is a class I non-classical HLA molecule with an
      important regulatory role on the immune response. The possible role of this
      molecule in the pathogenesis of SLE has not been explored. In this work, we
      evaluated the expression and function of HLA-G in SLE patients. We studied 37 SLE
      patients as well as 25 healthy donors. Peripheral blood monocytes and in vitro
      generated dendritic cells (DCs) were analyzed for HLA-G expression by flow
      cytometry. We found that monocytes from SLE patients as well as mature CD83+ DCs
      showed a diminished expression of HLA-G compared with healthy controls. In
      addition, monocytes from SLE patients showed a diminished induction of HLA-G
      expression in response to stimulation with IL-10. Furthermore, functional assays
      showed that these monocytes pre-treated with IFN-gamma exhibited a diminished
      capability to inhibit the proliferation of autologous lymphocytes. Finally,
      lymphocytes from SLE patients tended to display a lower acquisition of HLA-G (by
      trogocytosis) from autologous monocytes compared to controls. Our results might
      have implications for the immune abnormalities observed in patients with SLE.

PMID- 21188487
TI  - Examining the influence of family environments on youth violence: a comparison of
      Mexican, Puerto Rican, Cuban, non-Latino Black, and non-Latino White adolescents.
AB  - Existing research rarely considers important ethnic subgroup variations in
      violent behaviors among Latino youth. Thus, their risk for severe violent
      behaviors is not well understood in light of the immense ethnic and generational
      diversity of the Latino population in the United States. Grounded in social
      control theory and cultural analyses of familism, we examine differences in the
      risk for severe youth violence, as well its associations with family cohesion,
      parental engagement, adolescent autonomy, household composition, and immigrant
      generation among Mexican (n = 1,594), Puerto Rican (n = 586), Cuban (n = 488),
      and non-Latino Black (n = 4,053), and White (n = 9,921) adolescents with data
      from the National Longitudinal Study of Adolescent Health. Results indicate a
      gradient of risk; White youth had the lowest risk for severe violence and Puerto
      Rican youth had the highest risk compared to all other racial/ethnic subgroups.
      Within-group analysis indicates that family factors are not universally
      protective or risk-inducing. While family cohesion decreased the risk of severe
      violence among all groups, parental engagement was associated with increased risk
      among Blacks and Whites, and adolescent autonomy was associated with increased
      risk among Puerto Ricans and Cubans. In addition, Cuban and White adolescents who
      lived in single parent households or who did not live with their parents, had
      higher risk for severe violent behaviors than their counterparts who lived in two
      parent households. Among Latinos, the association of immigrant generation was in
      opposite directions among Mexicans and Cubans. We conclude that family and
      immigration factors differentially influence risk for violence among Latino
      subgroups and highlight the significance of examining subgroup differences and
      developing intervention strategies that are tailored to the needs of each ethnic
      subgroup.

PMID- 21188488
TI  - Pathways to sexual risk taking among female adolescent detainees.
AB  - Sexual risk taking among female delinquents represents a significant public
      health problem. Research is needed to understand the pathways leading to sexual
      risk taking among this population. This study sought to address this issue by
      identifying and testing two pathways from child maltreatment to non-condom use
      among 329 White and 484 African American female adolescent detainees: a
      relational pathway and a substance use coping pathway. The relational pathway
      indicated that child maltreatment would be related to non-condom use via
      depressive self-concept and condom use self-efficacy. The substance use coping
      pathway suggested that depressive self-concept and alcohol-based expectancies for
      sexual enhancement would mediate the relationship between child maltreatment and
      non-condom use. As hypothesized, the relational pathway variables were associated
      with one another in the expected directions; however, evidence of mediation was
      not found. Support for mediation was found for the substance use coping pathway.
      Exploratory across group comparison analysis indicated that the relational
      pathway was significant for White girls whereas the substance use coping pathway
      was significant for African American girls. Limitations and implications for
      future research are discussed.

PMID- 21188489
TI  - Brief report: perceptual load and the Autism Spectrum in typically developed
      individuals.
AB  - A fundamental task of the cognitive system is to prioritize behaviourally
      relevant sensory inputs for processing at the expense of irrelevant inputs. In a
      study of neurotypical participants (n = 179), we utilized a brief flanker
      interference task while varying the perceptual load of the visual display.
      Typically, increasing perceptual load (i.e., with greater numbers of search
      items) reduces interference from a competing peripheral distractor. We show that
      individuals who score above average on the Autism Spectrum Quotient (AQ) show
      stronger interference at high perceptual load than individuals with below-average
      AQ scores. This is consistent with recent findings in individuals with autism
      spectrum conditions, and supports the idea that the cognitive style of the
      autistic brain is reflected in a broader phenotype across the population.

PMID- 21188490
TI  - A conceptual model of interventions to increase diagnosis of acute HIV infection
      and reduce forward transmission.

PMID- 21188491
TI  - Repetitive element hypomethylation in blood leukocyte DNA and cancer incidence,
      prevalence, and mortality in elderly individuals: the Normative Aging Study.
AB  - BACKGROUND: Global genomic hypomethylation is a common epigenetic event in cancer
      that mostly results from hypomethylation of repetitive DNA elements. Case-control
      studies have associated blood leukocyte DNA hypomethylation with several cancers.
      Because samples in case-control studies are collected after disease development,
      whether DNA hypomethylation is causal or just associated with cancer development
      is still unclear. METHODS: In 722 elderly subjects from the Normative Aging Study
      cohort, we examined whether DNA methylation in repetitive elements (Alu, LINE-1)
      was associated with cancer incidence (30 new cases, median follow-up: 89 months),
      prevalence (205 baseline cases), and mortality (28 deaths, median follow-up: 85
      months). DNA methylation was measured by bisulfite pyrosequencing. RESULTS:
      Individuals with low LINE-1 methylation (<median) had a 3.0-fold (95%CI 1.3-6.9)
      increased incidence of all cancers combined. LINE-1 and Alu methylation were not
      significantly associated with cancer prevalence at baseline (all cancers
      combined). However, individuals with low LINE-1 methylation (<median) had a 3.2
      fold (95% CI 1.4-7.5) higher prevalence of lung cancer. Individuals with low LINE
      1 or Alu methylation (<median) had increased cancer mortality (HR = 3.2, 95%CI
      1.3-7.9 for LINE-1; HR = 2.5, 95%CI 1.1-5.8 for Alu). CONCLUSION: These findings
      suggest that individuals with lower repetitive element methylation are at high
      risk of developing and dying from cancer.

PMID- 21188492
TI  - Temporal trends in the black/white breast cancer case ratio for estrogen receptor
      status: disparities are historically contingent, not innate.
AB  - OBJECTIVE: For at least three decades, many investigators have reported on the US
      black/white breast cancer case ratio for estrogen receptor (ER) status as if it
      reflected an intrinsic biological difference. In light of racial/ethnic
      differences in declines in the incidence of ER+ breast cancer, as linked to
      changing use of hormone therapy, we empirically tested whether the black/white
      breast cancer estrogen receptor ratio has changed over time. METHODS: We examined
      temporal trends in the odds of being ER+ among white as compared to black women
      among all cases of invasive breast cancer occurring among women residing in the
      catchment area of the SEER 13 Registries Database between 1992 and 2005. RESULTS:
      During the study period, the odds of being ER+ among the white compared to black
      cases increased from 1992 to 2002 (a statistically significant joinpoint; p <
      0.05; peak odds ratio (2002) = 2.25 (95% confidence interval 2.13, 2.39)).
      Thereafter, the odds ratio leveled off (post-2002 slope not significantly
      different from zero; p = 0.326). Among women aged 45-54, moreover, the post-2002
      decline tended toward statistical significance (p = 0.0891). CONCLUSIONS: The
      results suggest the black/white breast cancer case estrogen receptor ratio is
      historically contingent, not innate.

PMID- 21188493
TI  - Has the lung cancer risk from smoking increased over the last fifty years?
AB  - BACKGROUND: We examine whether the lung cancer risk due to smoking has increased
      over time. METHODS: Lung cancer risk equations based on prospective mortality
      data collected from 1960 to 1972 were applied to 5-year birth-cohort-specific
      estimates of smoking behaviors among white males to estimate lung cancer
      mortality rates for U.S. white males from 1960 to 2000. These estimated rates
      were compared to U.S. white male mortality rates for the same birth cohorts.
      RESULTS: Observed birth-cohort-specific U.S. lung cancer mortality rates are
      substantially higher than those expected from changes in smoking behaviors, and
      the proportional difference increases with advancing calendar year. This trend
      persisted even when the duration term was increased in the risk equation.
      However, adjusting for changes in cigarette design over time by adding a term for
      the duration of smoking after 1972 resulted in the predicted rates closely
      approximating the observed U.S. mortality rates. CONCLUSION: Lung cancer risk
      estimates observed during the 1960s under predict current lung cancer mortality
      rates in U.S. white males. Adjustment for the duration of smoking after 1972
      results in estimates that reasonably approximate the observed U.S. lung cancer
      mortality, suggesting that lung cancer risks from smoking are increasing in the
      United States coincident with changes in cigarette design.

PMID- 21188494
TI  - Comparison of fertilization and embryonic development in sibling in vivo matured
      oocytes retrieved from different sizes follicles from in vitro maturation cycles.
AB  - PURPOSE: To examine the fertilization and developmental potential of sibling
      mature oocytes collected from different follicle sizes on day of retrieval in in
      vitro maturation (IVM) cycles. METHODS: Two hundred thirty eight hCG-primed IVM
      cycles were performed in 213 patients with polycystic ovaries. If sibling mature
      oocytes were retrieved on day of collection, they were divided into two groups,
      Group 1 (n = 78): M-II oocytes obtained from follicles size 10-14 mm; Group 2 (n
      = 192): M-II oocytes obtained from follicles size <10 mm. RESULTS: Of the 238
      cycles, 63 cycles had more than one M-II oocytes retrieved (total M-II oocytes =
      270) both from Groups 1 and 2. There were no significant differences between the
      two groups for oocyte diameter (117.2 mm vs. 116.9 mm), fertilization (79.5% vs.
      72.4%) and good quality embryo on day 3 (66.1% vs. 56.8%). CONCLUSIONS: The M-II
      oocytes retrieved from the cohort of follicles (<10 mm diameter) can produce the
      same quality of embryos as that from large follicles, likely contributing to
      improve the clinical outcome.

PMID- 21188495
TI  - Assisted reproduction in a patient with Klippel-Trenaunay syndrome: management of
      thrombophilia and consumptive coagulopathy.
AB  - Klippel-Trenaunay Syndrome (KTS) is a rare, sporadic triad of congenital
      malformations involving an extensive port wine stain, soft tissue or bone
      hypertrophy and underlying venous and/or lymphatic malformation involving an
      extremity. Pregnancy is known to exacerbate KTS complications and can put women
      at increased obstetrical risk due to deep venous thrombosis and other
      thromboembolic events. Here we report a case of a patient with KTS who achieved a
      pregnancy through in vitro fertilization (IVF) using her own eggs and a
      gestational surrogate in the setting of hypercoagulability and chronic
      consumptive coagulopathy.

PMID- 21188496
TI  - Haplotypes in the interleukin 8 gene and their association with chronic
      periodontitis susceptibility.
AB  - Interleukin-8 (IL-8), which is responsible for the migration and activation of
      neutrophils, is an important inflammatory mediator involved in the initiation and
      amplification of acute inflammatory reactions and chronic inflammatory processes.
      IL-8 plays an important role in periodontitis, an inflammatory disease
      characterized by the loss of connective tissue and alveolar bone. The aim of this
      study was to investigate whether the SNPs rs2227307 (+396) and rs2227306 (+781),
      and the haplotypes they formed together with the previously investigated rs4073 (
      251), were associated with chronic periodontitis susceptibility. Clinical
      periodontal exams were performed and DNA samples were collected from 493
      individuals (223 with periodontitis and 270 controls). Associations between SNPs,
      haplotypes, and subject phenotypes were analyzed using the chi(2) test followed
      by multivariate logistic regression modeling. We conclude that the +396TT
      genotype and the haplotypes ATC/TTC and AGT/TGC were significantly associated
      with chronic periodontitis susceptibility in Brazilians.

PMID- 21188497
TI  - Alternative splicing of human height-related zinc finger and BTB domain
      containing 38 gene through Alu exonization.
AB  - Recently, genome-wide association studies have identified a strong association
      between the ZBTB38 locus and human height. In a functional study, we detected two
      RT-PCR products of ZBTB38, amplified with primers in exons 7 and 8 from a
      chondrocyte cell line, C-28/I2. Sequencing revealed that the longer product
      contained an Alu segment in intron 7 of ZBTB38, which contained a potential
      splicing acceptor site that likely was used to generate the alternative
      transcript. Insertion of the Alu segment changed the consensus Kozak sequence of
      the ZBTB38 transcript, potentially altering translational efficiency. We
      performed RT-PCR using 16 tissue samples from humans and 8 tissue samples from
      primates to determine any tissue specificity or evolutionary conservation of the
      alternative splicing. Although we failed to identify any difference among the
      tissues, all primate samples expressed only the shorter Alu segment (lacking the
      transcript), suggesting that the alternative splicing event is hominid primate
      specific.

PMID- 21188498
TI  - Role of HLA allele polymorphism in chronic hepatitis B virus infection and HBV
      vaccine sensitivity in patients from eastern Turkey.
AB  - Human leukocyte antigen (HLA) alleles have been associated with the clinical
      outcomes of hepatitis B virus (HBV) infection, which range from spontaneous
      recovery to hepatocellular carcinoma. In this study involving subjects from
      eastern Turkey, the frequencies of HLA-B35, HLA-CW4, HLA-DQ2, and HLA-DQ8 were
      markedly higher in the chronic HBV group than those in the spontaneously
      recovered group; the frequencies of HLA-A11 and HLA-A24 in the nonresponsive HBV
      vaccine group were markedly higher than those in the responsive HBV vaccine
      group; and the frequency of HLA-CW6 in the nonresponsive HBV vaccine group was
      significantly lower than in the responsive group. A complete understanding of HLA
      types associated with the progression to chronic HBV infection and their effects
      within the cell at the molecular level will be an important contribution in the
      development of new HBV vaccines and new treatment strategies for chronic HBV
      infection.

PMID- 21188499
TI  - Development and characterization of microsatellite markers for genetic analysis
      of the swimming crab, Portunus trituberculatus.
AB  - This study isolated and characterized 11 novel microsatellite markers for the
      commercially important swimming crab species, Portunus trituberculatus. Genetic
      diversity and population structure of two populations of P. trituberculatus in
      the East China Sea were assessed using these loci. The microsatellite markers
      produced 242 alleles, varying from 17 to 26 alleles per locus. In all the
      samples, the range of heterozygosity was 0.6324-0.9403 (observed) and 0.8998
      0.9547 (expected). An F-statistic analysis revealed low genetic differentiation
      between the populations (mean F (ST) = 0.0197), with 98% of the variation
      resulting from the within-population component. In addition, cross-amplification
      was tested in two other portunid species, and we found that many loci yielded
      useful information. The high degree of polymorphism exhibited by the 11
      microsatellites suggests that these markers will be useful for both aquaculture
      and studies of natural populations of the genus.

PMID- 21188500
TI  - Antiangiogenic tyrosine kinase inhibition related gastrointestinal perforations:
      a case report and literature review.
AB  - Anti-VEGF (vascular endothelial growth factor) therapy with the monoclonal
      antibody bevacizumab can cause gastrointestinal (GI) perforations. In recent
      years it became apparent that GI perforations also occur during treatment with
      antiangiogenic tyrosine kinase inhibitors (TKIs). It is of clinical importance to
      consider (vague) abdominal complaints during antiangiogenic treatment as a sign
      of a GI perforation. To illustrate this serious complication, we report four
      cases of antiangiogenic treatment related GI perforations. In three cases this
      was due to antiangiogenic TKI treatment. Reported risk factors of GI perforations
      due to bevacizumab include the presence of a primary tumor in situ and recent
      history of endoscopy or abdominal radiotherapy. Pathology assessments of surgical
      removal of the perforated intestinal part reveal that perforations are
      predominantly seen at the tumor or anastomotic site, in case of carcinomatosis or
      diverticulitis or when GI obstruction or an intra-abdominal abscess is present.
      Whether the same risk factors may be involved in antiangiogenic TKI related GI
      perforations is unknown. The underlying mechanisms responsible for GI perforation
      during antiangiogenic treatment is unknown, but disturbance of host cell
      homeostasis of immune cells as well as platelet-endothelial cell interactions may
      play an important role. In conclusion, while clinical awareness that
      antiangiogenic treatment can cause GI perforations is critical for current
      medical practice, it is also very important to get more insight in its underlying
      mechanisms so that this life-threatening complication may be prevented in the
      near future.

PMID- 21188501
TI  - Vascular endothelial growth inhibitor (VEGI; TNFSF15) inhibits bone marrow
      derived endothelial progenitor cell incorporation into Lewis lung carcinoma
      tumors.
AB  - Bone marrow (BM)-derived endothelial progenitor cells (EPC) have a critical role
      in tumor neovascularization. Vascular endothelial growth inhibitor (VEGI) is a
      member of the TNF superfamily (TNFSF15). We have shown that recombinant VEGI
      suppresses tumor angiogenesis by specifically eliminating proliferating
      endothelial cells (EC). We report here that treatment of tumor bearing mice with
      recombinant VEGI leads to a significantly decreased population of BM-derived EPC
      in the tumors. We transplanted whole bone marrow from green fluorescent protein
      (GFP) transgenic mice into C57BL/6 recipient mice, which were then inoculated
      with Lewis lung carcinoma (LLC) cells. Intraperitoneal injection of recombinant
      VEGI led to significant inhibition of tumor growth and decrease of vasculature
      density compared to vehicle-treated mice. Tumor implantation yielded a decrease
      of BM-derived EPC in the peripheral blood, while VEGI-treatment resulted in an
      initial delay of such decrease. Analysis of the whole bone marrow showed a
      decrease of Lin(-)-c-Kit(+)-Sca-1(+) hematopoietic stem cell (HSC) population in
      tumor bearing mice; however, VEGI-treatment caused a significant increase of this
      cell population. In addition, the number of BM-derived EPC in VEGI-treated tumors
      was notably less than that in the vehicle-treated group, and most of the
      apoptotic cells in the VEGI-treated tumors were of bone marrow origin. These
      findings indicate that VEGI inhibits BM-derived EPC mobilization and prevents
      their incorporation into LLC tumors by inducing apoptosis specifically of BM
      derived cells, resulting in the inhibition of EPC-supported tumor vasculogenesis
      and tumor growth.

PMID- 21188503
TI  - Organochlorine pesticide (OCP) residues in cow's, buffalo's, and sheep's milk
      from Afyonkarahisar region, Turkey.
AB  - In this study, it was aimed to determine organochlorine pesticides (OCPs) in
      three types of milk (cow's, buffalo's, and sheep's milk) produced in
      Afyonkarahisar province of Turkey. The results indicated that these milk
      specimens were found to be contaminated by 21 different pesticides. Sixteen OCP
      residues were detected in sheep's milk and it was followed with 14 pesticides in
      buffalo's milk and 11 pesticides in cow's milk. Dominant pesticides in all
      samples examined were beta-HCH in buffalo's, cow's, and sheep's milk in the
      concentrations of 63.36, 91.32, and 122.98 ng/ml, respectively. Total OCP levels
      were found to be 243.81 ng/ml in sheep's milk, 151.02 ng/ml in cow's milk, and
      133.38 ng/ml in buffalo's milk. Some of the pesticides detected were found to be
      in the excess amount of the acceptable level regarding the EU regulations.

PMID- 21188504
TI  - Comparison of the changes in temperatures among rural, urban and metropolitan
      areas around the Inland Sea in Japan.
AB  - We investigated the changes in temperatures in Takamatsu, Tadotsu and Osaka areas
      in Japan. Data of temperatures in Takamatsu (urban area: 1942-2009), Tadotsu
      (rural area: 1893-2009) and Osaka (metropolitan area: 1883-2009) areas around the
      Inland Sea in Japan was obtained from Japan Meteorological Agency. The changes in
      temperatures in three areas in Japan were analyzed and compared. By using data
      from 1942 to 2009, various parameters of temperatures were significantly
      correlated with years. The changes in mean temperature in August and in a year in
      Takamatsu area for 50 years were highest (August: 1.6 degrees C, Year: 1.8
      degrees C) among three areas. In addition, correlation coefficient rate between
      years and the number of days over the level of 34 degrees C in August in
      Takamatsu area was highest (r = 0.567, p < 0.0001). Parameters of temperatures
      were gradually increased with years in all three areas. The heat island effect in
      Takamatsu area was similar to Osaka area in Japan.

PMID- 21188505
TI  - A probabilistic water quality index for river water quality assessment: a case
      study.
AB  - Available water quality indices have some limitations such as incorporating a
      limited number of water quality variables and providing deterministic outputs.
      This paper presents a hybrid probabilistic water quality index by utilizing fuzzy
      inference systems (FIS), Bayesian networks (BNs), and probabilistic neural
      networks (PNNs). The outputs of two traditional water quality indices, namely the
      indices proposed by the National Sanitation Foundation and the Canadian Council
      of Ministers of the Environment, are selected as inputs of the FIS. The FIS is
      trained based on the opinions of several water quality experts. Then the trained
      FIS is used in a Monte Carlo analysis to provide the required input-output data
      for training both the BN and PNN. The trained BN and PNN can be used for
      probabilistic water quality assessment using water quality monitoring data. The
      efficiency and applicability of the proposed methodology is evaluated using water
      quality data obtained from water quality monitoring system of the Jajrood River
      in Iran.

PMID- 21188506
TI  - Assessment of trace metals pollution in estuarine sediments using SEM-AVS and ERM
      ERL predictions.
AB  - This paper presents the distributions of the investigation of trace metals
      geochemistry in surface sediments of the Sergipe river estuary, northeast Brazil.
      Analyses were carried out by Flame or electrothermal atomic absorption
      spectrometry (FAAS or ETAAS). Principal component analysis was applied to results
      to identify any groupings among the different sampling sites. In order to
      determine the extent of contamination, taking into account natural variability
      within the region, metal concentrations were normalized relative to aluminium.
      Cr, Cu, Ni and Zn contamination was observed in sediments from the area receiving
      highest inputs of domestic wastes, while cadmium contamination occurred in
      sediments from the region affected by highest inflows of industrial effluents.
      Possible toxicity related to these metals was examined using the relationship
      simultaneously extracted metals/acid volatile sulfide and by comparing sediment
      chemical data with sediment quality guidelines ERL-ERM values. Results obtained
      using the two methods were in agreement and indicated that adverse effects on
      aquatic biota should rarely occur.

PMID- 21188507
TI  - Mercury concentrations in oligohaline wetland vegetation and associated soil
      biogeochemistry.
AB  - Concentrations of mercury were determined in above- and below-ground tissues of
      dominant plant species, as well as soils, in the wetlands of Lake Maurepas,
      Louisiana. Indicators of wetland soil biogeochemical status, such as soil redox
      potential, pore-water nutrient concentrations, and pore-water total sulfides,
      were also determined. Total mercury concentrations in plant tissues were within
      the typical range for vegetation not exposed to mercury contamination. Similarly,
      total mercury concentrations in soils were typical of uncontaminated wetlands
      within this geographic region. Soil methyl mercury levels in this study are
      slightly lower than those reported in other studies of nearby wetlands. This may
      reflect the less extensive geographic sampling in this study, or the low water
      levels in the Lake Maurepas system immediately prior to and during this study,
      which would have altered soil biogeochemical status. This is corroborated by
      measurements of soil redox potential and soil pore-water nitrogen and sulfur
      constituents conducted during this study that suggest minimal sulfate reduction
      was occurring in surficial soils. This study indicates that the wetlands
      surrounding Lake Maurepas are typical of many uncontaminated oligohaline wetlands
      in the southeastern U.S. in regard to mercury concentrations.

PMID- 21188508
TI  - A regional inventory and monitoring setup to evaluate bark peeling damage by red
      deer (Cervus elaphus) in coniferous plantations in Southern Belgium.
AB  - Bark peeling by red deer (Cervus elaphus L.) has become a serious issue for
      productive forests in western Europe. The damage is particularly severe on
      species such as spruce, as these become vulnerable to fungus attacks that result
      in considerably depreciated timber. This article presents a monitoring setup for
      recent bark peeling damage in spruce plantings in Wallonia (southern part of
      Belgium). This setup implies to collect data annually from a survey involving
      cluster sampling. It has been employed since 2004 in coniferous stands amounting
      to 165,000 ha of land, where Norway spruce is the predominant species. The study
      area was divided into blocks delineated along features preventing deer
      migrations. A set of indicators was computed either at the whole study area level
      or at block level. The resulting set of indicators enabled forest managers to
      follow up debarking intensity in productive forests. Additional analyses were
      carried out in order to assess the relationship between the social position of
      trees in the stand and the debarking probability on the one hand, and the
      relationship between the variation in damage magnitude and seasonality, namely
      summer versus winter, on the other hand.

PMID- 21188509
TI  - A critical review of field techniques employed in the survey of large woody
      debris in river corridors: a central European perspective.
AB  - In forested watersheds, large woody debris (LWD) is an integral component of
      river channels and floodplains. Fallen trees have a significant impact on
      physical and ecological processes in fluvial ecosystems. An enormous body of
      literature concerning LWD in river corridors is currently available. However,
      synthesis and statistical treatment of the published data are hampered by the
      heterogeneity of methodological approaches. Likewise, the precision and accuracy
      of data arising out of published surveys have yet to be assessed. For this
      review, a literature scrutiny of 100 randomly selected research papers was made
      to examine the most frequently surveyed LWD variables and field procedures. Some
      29 variables arose for individual LWD pieces, and 15 variables for wood
      accumulations. The literature survey revealed a large variability in field
      procedures for LWD surveys. In many studies (32), description of field procedure
      proved less than adequate, rendering the results impossible to reproduce in
      comparable fashion by other researchers. This contribution identifies the main
      methodological problems and sources of error associated with the mapping and
      measurement of the most frequently surveyed variables of LWD, both as individual
      pieces and in accumulations. The discussion stems from our own field experience
      with LWD survey in river systems of various geomorphic styles and types of
      riparian vegetation in the Czech Republic in the 2004-10 period. We modelled
      variability in terms of LWD number, volume, and biomass for three
      geomorphologically contrasting river systems. The results appeared to be
      sensitive, in the main, to sampling strategy and prevailing field conditions;
      less variability was produced by errors of measurement. Finally, we propose a
      comprehensive standard field procedure for LWD surveyors, including a total of 20
      variables describing spatial position, structural characteristics and the
      functions and dynamics of LWD. However, resources are only rarely available for
      highly time-demanding surveys. We therefore include a set of core LWD metrics for
      routine baseline surveys of individual LWD pieces (diameter, length, rootwad
      size, preservation of branches and rootwad, geomorphological/ecological function,
      stability/mobility) and wood accumulations (number of LWD pieces, geometrical
      dimensions, channel blockage, wood/air ratio), which may provide useful
      background information for river management, hydromorphological assessment,
      habitat evaluation, and inter-regional comparisons.

PMID- 21188510
TI  - Burial survival of benthic macrofauna following deposition of simulated dredged
      material.
AB  - In many coastal regions, the disposal of dredged material constitutes the largest
      (albeit often localised) anthropogenic disturbance to the seabed. Impacts can be
      minimised by reducing the amount of sediment overburden on the bed at any one
      time allowing short-term recovery to proceed via the vertical migration of
      resident species. However, there is currently a limited understanding of the
      ability of such species to successfully vertically migrate. This study presents
      the findings of a field experiment to investigate the vertical migratory
      capability of temperate macroinvertebrate species following the placement of
      simulated dredged material. The relationships between vertical migration success
      with sediment characteristics (organic carbon and sand content) and placement
      depth were explicitly examined. While the polychaete worms Tharyx sp. A. and
      Streblospio shrubsolii showed poor vertical migration with only 6 cm of sediment
      overburden, the oligochaete Tubificoides benedii showed some recovery while the
      gastropod mollusc Hydrobia ulvae exhibited good migratory success, even with 16
      cm of sediment overburden. While increases in sand content from 16% to 38% had no
      noticeable effect on vertical migration, increased sediment organic content from
      0.8% to 3.3% detrimentally affected vertical migratory activity. The results
      support the theory that species' survival following sediment burial is trophic
      group-related. The relevance of these findings with respect to dredged material
      disposal management is discussed.

PMID- 21188512
TI  - The quality of medical care, behavioral risk factors, and longevity growth.
AB  - The rate of increase of longevity has varied considerably across U.S. states
      since 1991. This paper examines the effect of the quality of medical care,
      behavioral risk factors (obesity, smoking, and AIDS incidence), and other
      variables (education, income, and health insurance coverage) on life expectancy
      and medical expenditure using longitudinal state-level data. We examine the
      effects of three different measures of the quality of medical care. The first is
      the average quality of diagnostic imaging procedures, defined as the fraction of
      procedures that are advanced procedures. The second is the average quality of
      practicing physicians, defined as the fraction of physicians that were trained at
      top-ranked medical schools. The third is the mean vintage (FDA approval year) of
      outpatient and inpatient prescription drugs. Life expectancy increased more
      rapidly in states where (1) the fraction of Medicare diagnostic imaging
      procedures that were advanced procedures increased more rapidly; (2) the vintage
      of self- and provider-administered drugs increased more rapidly; and (3) the
      quality of medical schools previously attended by physicians increased more
      rapidly. States with larger increases in the quality of diagnostic procedures,
      drugs, and physicians did not have larger increases in per capita medical
      expenditure. We perform several tests of the robustness of the life expectancy
      model. Controlling for per capita health expenditure (the "quantity" of
      healthcare), and eliminating the influence of infant mortality, has virtually no
      effect on the healthcare quality coefficients. Controlling for the adoption of an
      important nonmedical innovation also has little influence on the estimated
      effects of medical innovation adoption on life expectancy.

PMID- 21188511
TI  - Evaluation of genotoxicity in Rhamdia quelen (Pisces, Siluriformes) after sub
      chronic contamination with Fipronil.
AB  - Diverse genetic biomarkers have been used to evaluate the effects of pollution by
      mutagenic agents such as metals and pesticides, as well as a large variety of
      chemical substances derived from human activities. This work researched the
      effects that an exposure of 60 days to the insecticide Fipronil (concentrations
      of 0.05, 0.10 and 0.23 MUg/L) can cause in the fish Rhamdia quelen using Comet
      assay with gills, histopathological analysis of gills and the Piscine
      Micronucleus test and Nuclear Morphological Alterations. The results for the
      Comet assay and for gills histopathological injuries showed no difference between
      the control group and the contaminated groups. In the Piscine Micronucleus test,
      the smallest concentration of Fipronil (0.05 MUg/L) was similar as the control
      group, while concentrations of 0.10 and 0.23 MUg/L caused more damage to the DNA.
      These results suggested that only the highest concentrations of Fipronil tested
      cause damage in erythrocytes, but none of these concentrations was sufficient to
      alter the DNA in the gill cells. R. quelen may be a less sensitive bioindicator
      than other fish that have been tested. On the other hand, the concentrations used
      may not have been sufficient to detect alterations in the DNA of R. quelen with
      the chosen tests. Works like this take on great importance given the enormous
      quantity of substances that are thrown daily into the environment in an
      uncontrolled way, without evaluation of the consequences. The application of
      these tests with other concentrations, tissues and exposure times is suggested
      for future works.

PMID- 21188513
TI  - Caring, competence and professional identities in medical education.
AB  - This paper considers the multiple discourses that influence medical education
      with a focus on the discourses of competence and caring. Discourses of competence
      are largely constituted through, and related to, biomedical and clinical issues
      whereas discourses of caring generally focus on social concerns. These discourses
      are not necessarily equal partners in the enterprise of medical education.
      Discourses of competence tend to be privileged while those discourses of caring
      are often marginalised. Medical students learn to be physicians, and develop
      professional identities, in the context of these competing discourses. This paper
      documents a qualitative study designed to explore how professional identities are
      developed in the context of competing discourses. The study included a
      Foucauldian discourse analysis of medical education curriculum documents (67
      problem-based learning cases in total), 26 h of observation of a small group
      learning experience (a problem-based learning tutorial), and in-depth, open-ended
      interviews with five medical students and nine medical educators at a Canadian
      medical school. The paper describes how professional identities are developed in
      relation to discourses of competence, noting that students displayed what they
      considered to be desirable professional identities of confidence, capability and
      suitability. Also explored are the professional identities demonstrated in
      relation to discourses of caring, including those of benevolence and humbleness.
      Despite current conceptualisations, medical education is ripe with potential. The
      data indicate Foucauldian "spaces of freedom"-sites at which the complexity of
      the practice of medicine and the interwoven natures of the discourses of
      competence and caring might be taken into account as a means of challenging taken
      for granted cultural norms and broadening the medical gaze.

PMID- 21188514
TI  - Workplace learning from a socio-cultural perspective: creating developmental
      space during the general practice clerkship.
AB  - Workplace learning in undergraduate medical education has predominantly been
      studied from a cognitive perspective, despite its complex contextual
      characteristics, which influence medical students' learning experiences in such a
      way that explanation in terms of knowledge, skills, attitudes and single
      determinants of instructiveness is unlikely to suffice. There is also a paucity
      of research which, from a perspective other than the cognitive or descriptive
      one, investigates student learning in general practice settings, which are often
      characterised as powerful learning environments. In this study we took a socio
      cultural perspective to clarify how students learn during a general practice
      clerkship and to construct a conceptual framework that captures this type of
      learning. Our analysis of group interviews with 44 fifth-year undergraduate
      medical students about their learning experiences in general practice showed that
      students needed developmental space to be able to learn and develop their
      professional identity. This space results from the intertwinement of workplace
      context, personal and professional interactions and emotions such as feeling
      respected and self-confident. These forces framed students' participation in
      patient consultations, conversations with supervisors about consultations and
      students' observation of supervisors, thereby determining the opportunities
      afforded to students to mind their learning. These findings resonate with other
      conceptual frameworks and learning theories. In order to refine our
      interpretation, we recommend that further research from a socio-cultural
      perspective should also explore other aspects of workplace learning in medical
      education.

PMID- 21188515
TI  - Increases in mRNA and DREAM protein expression in the rat spinal cord after
      formalin induced pain.
AB  - Downstream Regulatory Element Antagonist Modulator (DREAM) protein modulates pain
      by regulating prodynorphin gene transcription. Therefore, we investigate the
      changes of mRNA and DREAM protein in relation to the mRNA and prodynorphin
      protein expression on the ipsilateral side of the rat spinal cord after formalin
      injection (acute pain model). DREAM like immunoreactivity (DLI) was not
      significantly different between C and F groups. However, we detected the
      upregulation of mean relative DREAM protein level in the nuclear but not in the
      cytoplasmic extract in the F group. These effects were consistent with the
      upregulation of the relative DREAM mRNA level. Prodynorphin like immunoreactivity
      (PLI) expression increased but the relative prodynorphin mRNA level remained
      unchanged. In conclusion, we suggest that upregulation of DREAM mRNA and protein
      expression in the nuclear compartment probably has functional consequences other
      than just the repression of prodynorphin gene. It is likely that these mechanisms
      are important in the modulation of pain.

PMID- 21188516
TI  - Total and mitochondrial nitrosative stress, decreased brain-derived neurotrophic
      factor (BDNF) levels and glutamate uptake, and evidence of endoplasmic reticulum
      stress in the hippocampus of vitamin A-treated rats.
AB  - Vitamin A supplementation has caused concern among public health researchers due
      to its ability in decreasing life quality from acute toxicological effects to
      increasing mortality rates among vitamin supplement users. For example, it was
      described cognitive decline (i.e. irritability, anxiety, and depression) in
      patients subjected to long-term vitamin A therapy, as occurs in cancer treatment.
      However, the mechanism by which vitamin A affects mammalian cognition is not
      completely understood. Then, we performed the present work to investigate the
      effects of vitamin A supplementation at clinical doses (1,000-9,000 IU/kg day(
      1)) for 28 days on rat hippocampal nitrosative stress levels (both total and
      mitochondrial), bioenergetics states, brain-derived neurotrophic factor (BDNF),
      alpha- and beta-synucleins, BiP and dopamine receptor 2 (D2 receptor) contents,
      and glutamate uptake. We observed mitochondrial impairment regarding respiratory
      chain function: increased complex I-III, but decreased complex IV enzyme
      activity. Also, decreased BDNF levels were observed in vitamin A-treated rats.
      The present data demonstrates, at least in part, that mitochondrial dysfunction
      and decreased BDNF and D2 receptors levels, as well as decreased glutamate uptake
      may take an important role in the mechanism behind the previously reported
      cognitive disturbances associated to vitamin A supplementation.

PMID- 21188517
TI  - Neurochemical correlates of alloxan diabetes: glucose and related brain
      metabolism in the rat.
AB  - Diabetes mellitus is known to impair glucose metabolism. The fundamental
      mechanism underlying hyperglycaemia in diabetes mellitus involves decreased
      utilization of glucose by the brain. However, mechanisms responsible for
      progressive failure of glycaemic regulation in type I (IDDM) diabetes need
      extensive and proper understanding. Hence the present study was initiated. Type I
      diabetes was induced in albino rat models with alloxan monohydrate (40 mg/Kg iv).
      Cerebral cortex and medulla oblongata were studied 48 h after alloxanisation.
      Diabetes caused an elevation in glucose, glutamate, aspartate, GABA and taurine
      levels and a decline in the glutamine synthetase activity. The activities of
      brain lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) exhibited
      significant decrease during diabetes. Ammonia content increased (P < 0.01) as a
      function of diabetes. Na(+)-K(+) ATPase showed an elevation (P < 0.01) and Ca(++)
      ATPase activity decreased (P < 0.01). Calcium content enhanced (P < 0.05) in the
      brain of diabetic rats. A General increase in the brain AMP, ADP and ATP was
      found on inducing diabetes. Impaired cerebral glucose metabolism accounts for the
      failure of cerebral glucose homeostasis. The impairment in the glycaemic control
      leads to disturbances in cerebral glutamate content (resulting in calcium
      overload and excitotoxic injury) and brain energy metabolism as reflected by
      alterations occurring in adenine nucleotide and the ATPases. The failure in the
      maintenance of normal energy metabolism during diabetes might affect glucose
      homeostasis leading to gross cerebral dysfunction during diabetes.

PMID- 21188518
TI  - Long-term cultures of stem/progenitor cells from lobular and ductal breast
      carcinomas under non-adherent conditions.
AB  - A small subpopulation of stem/progenitor cells can give rise to the diversity of
      differentiated cells that comprise the bulk of the tumor. Are proliferating
      cells, within the bulk of tumor, few cells with uncommon features? The cell
      biological approach provides a limitless model for studying the hierarchical
      organization of progenitor subpopulation and identifying potential therapeutic
      targets. Aim of the study was to expand patients' breast cancer cells for
      evaluating functional cell properties, and to characterize the protein expression
      profile of selected cells to be compared with that of primary tumors. Breast
      cancer cells from estrogen receptor (ERalpha) positive, HER2 negative lobular
      (LoBS cells) and ductal (DuBS cells) histotype were cultured under non-adherent
      conditions to form mammospheres. Sorting of the cells by their surface expression
      of CD24 and CD44 gave rise to subpopulations which were propagated, enriched and
      characterized for the expression of epithelial and stromal markers. We found that
      non-adherent culture conditions generate mammospheres of slowly proliferating
      cells; single cells, dissociated from mammospheres, grow in soft agar; long-term
      cultured LoBS and DuBS cells, CD44+/CD24low, express cytokeratin 5 (CK5), alpha
      smooth muscle actin (alpha-sma) and vimentin, known as markers of
      basal/myoepithelial cells; and ERalpha (only DuBS cells), HER1 (EGF-Receptor),
      activated HER2, and cyclinD1 as markers of luminal epithelial cell. Isolates of
      cells from breast cancer patients may be a tool for a marker-driven testing of
      targeted therapies.

PMID- 21188519
TI  - Slaughter stock abattoir survey of carcasses and organ/offal condemnations in
      Arusha region, northern Tanzania.
AB  - The current study reviews a 3-year record of slaughtered animals in Arusha
      abattoir to determine the causes of carcasses and organ/offal condemnations. A
      total of 115,186 cattle, 61,551 sheep, 37,850 goats and 13,310 pigs were
      slaughtered. Out of the slaughtered cattle, 8.6% were pregnant. Up to 125
      (0.108%), 39 (0.063%), 40 (0.106%) and 132 (0.992%) of all cattle, sheep, goats
      and pig carcasses, respectively, were totally condemned. Cysticercosis was the
      leading cause of total carcass condemnations in cattle (0.051%) and in pig
      (1.397%), while emaciation accounted for 0.045% and 0.074% of carcass
      condemnations in sheep and goats, respectively. Livers and lungs were the most
      condemned organs in all four animal species. The main cause of condemnations of
      cattle livers was fasciolosis (8.6%), while stilesiosis in sheep and goats
      accounted for 8.1% and 7.3%, respectively. Ascariasis (4.03%) was the only cause
      of liver condemnation in pigs. Pneumonia was the leading cause of lung
      condemnations at the rates of 3.99%, 2.43% and 2.83% in cattle, sheep and goats,
      respectively. Because of their zoonotic nature, occurrences of hydatidosis,
      cysticercosis, fasciolosis and tuberculosis may pose a public health risk. Thus,
      there is a need to introduce appropriate control measures of livestock diseases
      to minimise the rate of infection and reduce economic losses.

PMID- 21188520
TI  - Halomonas aidingensis sp. nov., a moderately halophilic bacterium isolated from
      Aiding salt lake in Xinjiang, China.
AB  - Two Gram-negative moderately halophilic bacterial strains, designated Ad-1(T) and
      C-12, were isolated from Aiding salt lake of Xinjiang in China. The novel
      isolates were subjected to a polyphasic taxonomic study. Cells of these strains
      were cocci or short rods and motile with polar flagella. Colonies produced brown
      red pigment. The isolates grew in the range of 0.5-25% (w/v) NaCl, pH 5.5-10.5
      and 4-45 degrees C. Analysis of their 16S rRNA gene sequences indicated that
      strains Ad-1(T) and C-12 belonged to the genus Halomonas showing 92.7-98.4%
      similarity with the type species. The isoprenoid quinones of the isolates were Q
      9 and Q-8. The major cellular fatty acids were C18:1omega7c, C16:1omega7c/6c,
      C16:0, C12:0-3OH and C10:0. The DNA G + C contents of strains Ad-1(T) and C-12
      were 64.6 and 63.9 mol%, respectively. The DNA relatedness between the two
      isolates was 89.2%. The similarities of these newly isolated strains with closely
      related type strains were lower than 35% at the genetic level. Based on
      phenotypic, chemotaxonomic and genetic characteristics, the representative strain
      Ad-1(T) is considered to be a novel species of the genus Halomonas, for which the
      name Halomonas aidingensis sp. nov. is proposed, with Ad-1(T) (= CGMCC 1.10191(T)
      = NBRC 106173(T)) as the type strain.

PMID- 21188521
TI  - Differential effects of vitamin K1 on AFP and DCP levels in patients with
      unresectable HCC and in HCC cell lines.
AB  - PURPOSE: DCP is a useful HCC tumor marker, which reflects a defect in vitamin K
      metabolism. We tested the hypothesis that vitamin K treatment of HCC patients
      might suppress this marker and possibly AFP also. EXPERIMENTAL DESIGN: HCC
      patients who had both elevated AFP and DCP were included. A phase I cohort was
      treated with escalating vitamin K1 intravenous weekly doses and a 27-patient
      phase II cohort was then treated with a fixed oral daily dose. RESULTS: A maximum
      tolerated dose was not reached up to 100-fold the normal vitamin K1 dose. No
      toxicities were found up to 1,000 mg/infusion. In the phase II cohort, 93% of
      patients had tumor marker responses by decreased DCP levels, but only 22% had
      responses by decreased AFP levels. CT scans showed 11% of patients had PRs, 59%
      had stable tumors and 29.6% had tumor progression. Mechanism studies showed that
      vitamin K1 induced phosphorylation of JNK and c-Jun and caspase-mediated
      apoptosis. CONCLUSIONS: Vitamin K1 was non-toxic at high doses, strongly
      inhibited plasma DCP levels, but weakly suppressed AFP levels. The results
      provide evidence that the two tumor markers are not directly linked and that DCP
      levels may not reflect HCC cell growth, as DCP levels were decreased in patients
      without AFP change, and were suppressed in vitro at 1% of the vitamin K1
      concentration needed to inhibit AFP.

PMID- 21188522
TI  - Narrow-banding images and structures of microvessels of colonic lesions.
AB  - BACKGROUND: Magnifying colonoscopy with NBI has been shown to be useful for the
      differential diagnosis of tumors. However, the relationship between findings on
      NBI magnification and the microvessel architecture of colorectal lesions remains
      to be clarified. AIMS: The aim of this study was to clarify the correlation
      between NBI findings and the microvascular architecture of colorectal lesions
      according to the depth of microvessels from the mucosal surface. METHODS: A total
      of 22 colorectal lesions (11 tubular adenomas and 11 hyperplasia) obtained from
      22 patients were studied. These lesions were analyzed microscopically on tissue
      specimens immunostained with CD34. Three-dimensional images were reconstructed
      from serial sections of tubular adenomas, hyperplasia, and normal mucosa.
      RESULTS: Three-dimensional reconstructed images of tubular adenoma and normal
      mucosa to a depth of less than 150 MUm from the mucosal surface showed similar
      structures to images obtained by NBI magnification. Microvessel diameter was
      significantly larger in tubular adenoma than in normal mucosa (P = 0.002) and
      hyperplasia (P = 0.034), and microvessel area was significantly larger in tubular
      adenoma than in normal mucosa (P < 0.001) and hyperplasia (P < 0.001) only in the
      superficial mucosal layer (to a depth of less than 150 MUm). CONCLUSIONS: TA was
      characterized by thicker microvessels and higher volume of microvessels than NM
      and HP. Compared with white light, NBI can more accurately depict the
      characteristics of microvessels because it uses light with short wavelengths,
      thereby contributing to high diagnostic capability.

PMID- 21188523
TI  - Myenteric denervation downregulates galectin-1 and -3 expression in gastric
      carcinogenesis.
AB  - BACKGROUND: This study evaluated the galectin-1 and -3 expression during N-methyl
      N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in denervated
      rat stomachs using benzalkonium chloride. METHOD: Four experimental situations
      were evaluated: nondenervated and denervated stomachs without lesions and
      nondenervated and denervated stomachs with lesions. Sections of the pyloric
      region were stained with toluidine blue and incubated with mouse monoclonal anti
      Gal-1 and rabbit polyclonal anti-Gal-3 for histopathological and
      immunohistochemical analysis, respectively. RESULT: MNNG caused the development
      of benign and malignant epithelial lesions, which were more pronounced in
      nondenervated stomachs with lesions and accompanied by inflammatory cell-enriched
      stroma. By immunostaining, the epithelial cells, blood vessels, muscle layer, and
      myenteric plexus were Gal-1 and -3 positive. Gal-3 was also detected in the
      gastric crypts, mucus secretion, and fibroblasts of pyloric fragments.
      Development of lesions in denervated stomachs was associated with a significant
      decrease in Gal-1 and -3 expression in epithelial cells, mast cells, and
      neutrophil cytoplasm, compared with that of nondenervated stomach lesions (P <
      0.01; P < 0.001; P < 0.001, respectively). CONCLUSION: These results demonstrate
      that myenteric denervation downregulates endogenous Gal-1 and -3 expression,
      which might inhibit tumor development in this experimental model.

PMID- 21188524
TI  - Pancreato-biliary malignancy diagnosed by endoscopic ultrasonography in absence
      of a mass lesion on transabdominal imaging: prevalence and predictors.
AB  - BACKGROUND AND AIMS: Pancreatic adenocarcinoma is the fourth leading cause of
      cancer-related death in the United States. Pancreatic cancer is diagnosed in some
      patients by endoscopic ultrasonography (EUS) even in the absence of an obvious
      mass lesion on transabdominal imaging studies. The purpose of this study was to
      estimate the prevalence of PBM on EUS-FNA in patients with no obvious mass on
      transabdominal imaging and identify possible predictors of PBM in this cohort of
      patients. METHODS: Three hundred and twenty-six patients (219 female; mean age:
      57) with no obvious neoplastic lesion on trans-abdominal imaging underwent EUS.
      Demographic data, indication of EUS, history of weight loss, smoking, alcohol
      use, diabetes, cholecystectomy status, CT and USG findings, and liver function
      tests (LFTs) were reviewed. RESULTS: Thirty patients (9%) were diagnosed with a
      PBM by EUS-FNA (27 pancreatic adenocarcinoma, three ampullary adenocarcinoma).
      The mean age of patients diagnosed with PBM was significantly (P < 0.01) higher
      than controls. The mean size of the tumor was 2.8 cm (range: 0.9-7 cm). Male
      gender, presence of jaundice, abnormal LFTs, weight loss, and nonspecific trans
      abdominal imaging results such as dilated common bile duct (CBD), and abnormal
      appearing pancreas predicted the presence (P < 0.05) of PBM, whereas patients
      with previous cholecystectomy and abdominal pain were less likely to have this
      diagnosis. CONCLUSIONS: Normal trans-abdominal imaging does not completely
      exclude the presence of PBM. Nonspecific pancreatic abnormalities and CBD
      dilation on trans-abdominal imaging, with jaundice, abnormal LFTs, weight loss,
      and lack of abdominal pain are predictors of PBM.

PMID- 21188525
TI  - Dietary history and physical activity and risk of advanced liver disease in
      veterans with chronic hepatitis C infection.
AB  - BACKGROUND: The role of customary diet and physical activity in development of
      advanced HCV-related liver disease is not well-established. METHODS: We conducted
      a retrospective association study in 91 male veterans with PCR-confirmed chronic
      HCV and biopsy-determined hepatic pathology. Respondents completed the Block Food
      Frequency and the International Physical Activity questionnaires. We conducted
      three independent assessments based on hepatic pathology: fibrosis (advanced = F3
      F4 vs. mild = F1-F2), inflammation (advanced = A2-A3 vs. mild = A1) and steatosis
      (advanced = S2-S3 vs. mild = S1). Each assessment compared estimated dietary
      intake and physical activity in veterans with advanced disease to that in
      analogous veterans with mild disease. Multivariate models adjusted for total
      calories, age, race/ethnicity, biopsy-to-survey lag-time, BMI, pack-years
      smoking, and current alcohol use. RESULTS: Average veteran age was 52, with 48%
      African-American. Advanced fibrosis was more prevalent than advanced inflammation
      or steatosis (52.7% vs. 29.7% vs. 26.4%, respectively). The strongest
      multivariate association was the suggestive 14-fold significantly decreased
      advanced fibrosis risk with lowest dietary copper intake (OR = 0.07, 95% CI 0.01
      0.60). Other suggestive associations included the 6.5-fold significantly
      increased advanced inflammation risk with lower vitamin E intake and 6.2-fold
      significantly increased advanced steatosis risk with lower riboflavin intake. The
      only physical activity associated with degree of hepatic pathology was a two-fold
      greater weekly MET-minutes walking in veterans with mild compared to advanced
      steatosis (P = 0.02). CONCLUSIONS: Several dietary factors and walking may be
      associated with risk of advanced HCV-related liver disease in male veterans.
      However, given our modest sample size, our findings must be considered as
      provisional pending verification in larger prospective studies.

PMID- 21188526
TI  - Effect of cadmium on photosystem II activity in Chlamydomonas reinhardtii:
      alteration of O-J-I-P fluorescence transients indicating the change of apparent
      activation energies within photosystem II.
AB  - In this study, we evaluated how cadmium inhibitory effect on photosystem II and I
      electron transport may affect light energy conversion into electron transport by
      photosystem II. To induce cadmium effect on the photosynthetic apparatus, we
      exposed Chlamydomonas reinhardtii 24 h to 0-4.62 MUM Cd(2+). By evaluating the
      half time of fluorescence transients O-J-I-P at different temperatures (20-30
      degrees C), we were able to determine the photosystem II apparent activation
      energies for different reduction steps of photosystem II, indicated by the O-J-I
      P fluorescence transients. The decrease of the apparent activation energies for
      PSII electron transport was found to be strongly related to the cadmium-induced
      inhibition of photosynthetic electron transport. We found a strong correlation
      between the photosystem II apparent activation energies and photosystem II oxygen
      evolution rate and photosystem I activity. Different levels of cadmium inhibition
      at photosystem II water-splitting system and photosystem I activity showed that
      photosystem II apparent activation energies are strongly dependent to photosystem
      II donor and acceptor sides. Therefore, the oxido-reduction state of whole
      photosystem II and I electron transport chain affects the conversion of light
      energy from antenna complex to photosystem II electron transport.

PMID- 21188527
TI  - Use of a SPAD-502 meter to measure leaf chlorophyll concentration in Arabidopsis
      thaliana.
AB  - The SPAD-502 meter is a hand-held device that is widely used for the rapid,
      accurate and non-destructive measurement of leaf chlorophyll concentrations. It
      has been employed extensively in both research and agricultural applications,
      with a range of different plant species. However, its utility has not been fully
      exploited in relation to the most intensively studied model organism for plant
      science research, Arabidopsis thaliana. Measurements with the SPAD-502 meter
      produce relative SPAD meter values that are proportional to the amount of
      chlorophyll present in the leaf. In order to convert these values into absolute
      units of chlorophyll concentration, calibration curves must be derived and
      utilized. Here, we present calibration equations for Arabidopsis that can be used
      to convert SPAD values into total chlorophyll per unit leaf area (nmol/cm(2);
      R(2) = 0.9960) or per unit fresh weight of leaf tissue (nmol/mg; R(2) = 0.9809).
      These relationships were derived using a series of Arabidopsis chloroplast
      biogenesis mutants that exhibit chlorophyll deficiencies of varying severity, and
      were verified by the subsequent analysis of senescent or light-stressed leaves.
      Our results revealed that the converted SPAD values differ from photometric
      measurements of solvent-extracted chlorophyll by just ~6% on average.

PMID- 21188528
TI  - Barriers to health care for Burmese migrants in Phang Nga province, Thailand.
AB  - The article describes barriers to health care experienced by Burmese migrants in
      a province of Thailand based on the experience of Medecins Sans Frontieres over
      the past three years. In addition to the barriers, the article makes suggestions
      for improving the conditions for the migrant workers.

PMID- 21188529
TI  - Immigration, income, drinking and obesity in African American adults.
AB  - The objective of this study was to investigate the relationship between
      immigration status, income, drinking and overweight and obesity in African
      American adults residing in the United States using an internet web based survey.
      Data on 303 adult African American immigrants and non-immigrants was collected
      using a self-administered web based survey. Respondents were recruited using a
      snowball sampling technique to obtain a convenience sample. Multiple logistic
      regression analysis were used to test the independent effects of the immigration
      status while controlling for confounding effects of demographic, social and
      behavioral variables. The results of the study showed no significant difference
      between obesity and immigration status in black adults residing in the US
      (adjusted odds ration = 1.1095, P = 0.7489). Significance at the P < 0.05 level
      was demonstrated for obesity and two independent variables: age (OR = 1.0332, P =
      0.0298) and days per month consumed more than 5 alcoholic beverages (OR = 1.7735,
      P = 0.0001). Adult African American immigrants in this study sample were not at
      risk of being obese due to their immigration status. However, age and days in a
      month in which more than 5 alcoholic beverages are consumed were significant risk
      factors for obesity. Primary care providers should be alert for obesity and
      alcohol consumption in this population.

PMID- 21188530
TI  - Disability pension rates among immigrants in Norway.
AB  - Immigrants from low-income countries are more likely than ethnic Norwegians to
      receive disability pensions. In a previous study in Oslo, we showed that
      occupational position probably accounted for all of this difference. The present
      article presents a study of the total population, with data on education and age
      at receipt of pension. Census and social security data for all persons living in
      Norway from 1992 to 2003 were used to identify new disability pensions to those
      aged 30-55 years and eligible in 1992, comprising 15.9% females and 11.4% males.
      Age-adjusted relative risk was 2.03 (95% CI 1.97-2.08) for non-Western males and
      1.30 (1.26-1.36) for non-Western females compared with Westerners, and more than
      three times higher for males from North Africa/the Middle East. Education did not
      explain any of the risk differences, but when adjusting for age at pension
      receipt the differences disappeared completely. This is probably due to their
      being in predominantly unskilled occupations where there is also a low pension
      age among ethnic Norwegians.

PMID- 21188531
TI  - Patients from abroad becoming patients in everyday practice: torture survivors in
      primary care.
AB  - Since 1975, over 3.5 million refugees have resettled in the United States, many
      of whom have experienced some form of torture, and little data exists on their
      primary care needs. This is retrospective chart-review of sixty-one torture
      survivors in Denver, Colorado. The patients were predominantly from Africa, 88%
      experienced physical torture, 21% sexual torture. Medical conditions included:
      major depression (45%), PTSD (48%), anxiety (31%), insomnia (50%), hypertension
      (29%), dyslipidemia (6%), HIV (6%) and tuberculosis class 2-4 (32%). Physical
      torture increased rates of PTSD (OR 7.29; CI 1.81, 29.45) and insomnia (OR 5.08;
      CI 1.41, 18.34). Sexual torture increased rates of major depression (OR 5.44; CI
      1.29, 22.99), PTSD (OR 8.24; CI 1.61, 42.18), and insomnia (OR 6.84; CI 1.34,
      34.90). Somatic complaints were more frequent in those who had experienced sexual
      torture (P = 0.041). Torture survivors have complex primary care needs, requiring
      multidisciplinary treatment.

PMID- 21188532
TI  - 911 (nueve once): Spanish-speaking parents' perspectives on prehospital emergency
      care for children.
AB  - Racial, ethnic and language-based disparities occur throughout the US health
      system. Pediatric prehospital emergency medical services are less likely to be
      used by Latinos. We identified perceptions of and barriers to prehospital
      pediatric emergency care (911) access among Spanish-speaking parents. A
      qualitative study involving six focus groups was conducted. Spanish-speaking
      parents participated with a bilingual moderator. Topics discussed included
      experiences, knowledge, beliefs, fears, barriers, and improvement strategies. All
      groups were audiotaped, transcribed, and reviewed for recurring themes. Forty
      nine parents participated. Though parents believed 911 was available to all, many
      were uncertain how to use it, and what qualified as an emergency. Barriers
      included language discordance, fear of exposing immigration status, and fear of
      financial consequences. Parents strongly desired to learn more about 911 through
      classes, brochures, and media campaigns. Prehospital emergency care should be
      available to all children. Further quantitative studies may help solidify the
      identified barriers and uncover areas needing improvement within Emergency
      Medical Systems. Addressing barriers to 911 use in Spanish-speaking communities
      could improve the equity of health care delivery, while also decreasing the
      amount of non-emergency 911 use.

PMID- 21188533
TI  - An association between DNA repair gene polymorphisms and survival in patients
      with resected non-small cell lung cancer.
AB  - DNA repair genetic polymorphisms have been studied extensively in relation to
      lung cancer susceptibility, but much less is known about their role in clinical
      outcome modulation. In this report, we examined effect of the XPA -4G>A, XPD
      Asp312Asn, Leu751Gln, hHR23B Ala249Val, XPG Asp1104His, XRCC1 Arg399Gln, XRCC2 
      4234G>C and XRCC3 Thr241Met polymorphisms on overall survival in 162 patients
      with resected non-small cell lung cancer (NSCLC). The XRCC3 Met/Met genotype was
      significantly associated with increased risk of death among all patients and men
      in uni- and multivariate analyses. The risk was higher for adenocarcinoma
      patients possessing the XRCC3 Met/Met or XRCC1 Gln/Gln genotypes, although their
      frequency was small. The XRCC1 399Gln allele was also associated with poor
      prognosis in stage II-IIIA and among older individuals. Men homozygous for the
      XPD 312 Asn/Asn had significantly better survival with the risk of death being at
      borderline significance in uni- and multivariate models. Younger cases and ever
      smokers smoking less than median pack-years showed significantly increased risk
      of death associated with the XPA -4A allele. A presence of one or two XRCC2 
      4234C alleles had a protective effect in males and ever smokers with lower
      cumulative smoking dose, although the CC genotype was rarely observed. When
      number of combined risk alleles was considered, we found that carriers of >4
      adverse alleles were at significantly increased risk of death in uni- and
      multivariate models. Therefore, our results indicate that selected genetic
      polymorphisms in DNA repair genes may influence overall survival in resected
      NSCLC.

PMID- 21188534
TI  - Overexpression of osteopontin in hepatocellular carcinoma and its relationships
      with metastasis, invasion of tumor cells.
AB  - Osteopontin (OPN) plays an important role in metastasis and relapse of human
      cancer. However, the whole story of OPN relating to cancer has been far from
      clear untill now. To investigate the expression of OPN in hepatocellular
      carcinoma (HCC) and its relationships with recurrence and metastasis of HCC,
      normal and malignant liver tissues from patients with HCC were analyzed using
      immunohistochemical staining. OPN expression was inhibited by small interfering
      RNA (siRNA) in HCC cells lines, and then colony formation and matrigel invasion
      were examined. The results showed that expression of OPN was associated with
      metastasis of HCC with a positive rate of OPN in the tissue of HCC (70.00%),
      which was highly more obvious than those in paracarcinoma tissue and normal liver
      tissue (P < 0.01). In HCC cell lines, OPN depletion could reduce formed colony
      and metastasizing numbers in vitro. In conclusion, Expression of OPN in the
      tissue of HCC is related to metastasis or metastases. Specific siRNA could
      decrease expressions of OPN at both mRNA and protein levels, and abates the
      invasiveness of hepatocellular carcinoma cells, suggesting that OPN might be a
      promising agent for treatment of metastasis and recurrence of HCC.

PMID- 21188535
TI  - Replicative senescence of human bone marrow and umbilical cord derived
      mesenchymal stem cells and their differentiation to adipocytes and osteoblasts.
AB  - Mesenchymal stem cells (MSC) which have self-renewal and multiple differentiation
      potential in vitro play important roles in regenerative medicine and tissue
      engineering. However, long-term culture in vitro leads to senescence which
      results in the growth arrest and reduction of differentiation. In this study, MSC
      derived from human bone-marrow (BM-MSC) and umbilical cord (UC-MSC) were cultured
      in vitro lasted to senescence. Senescence and apoptosis detection showed that the
      senescent cells increased significantly but the increase of apoptosis was not
      significant in the long term culture. Senescence related genes p16, p21 and p53
      increased gradually in BM-MSC. However, p16 and p53 reduced and then increased
      but with the gradual increase of p21 in UC-MSC. Adipogenic differentiation
      decreased whereas the propensity for osteogenic differentiation increased in
      senescent MSC. Real time RT-PCR demonstrated that both C/EBPalpha and PPARgamma
      decreased in senescent BM-MSC. However, in UC-MSC, PPARgamma decreased but
      C/EBPalpha increased in late phase compared to early phase. The study
      demonstrated p21 was important in the senescence of BM-MSC and UC-MSC. C/EBPalpha
      and PPARgamma could regulate the balance of adipogenic differentiation in BM-MSC
      but only PPARgamma not C/EBPalpha was involved in the adipogenic differentiation
      in UC-MSC.

PMID- 21188536
TI  - Cellular mechanisms of bone remodeling.
AB  - Bone remodeling is a tightly regulated process securing repair of microdamage
      (targeted remodeling) and replacement of old bone with new bone through
      sequential osteoclastic resorption and osteoblastic bone formation. The rate of
      remodeling is regulated by a wide variety of calcitropic hormones (PTH, thyroid
      hormone, sex steroids etc.). In recent years we have come to appreciate that bone
      remodeling proceeds in a specialized vascular structure,--the Bone Remodeling
      Compartment (BRC). The outer lining of this compartment is made up of flattened
      cells, displaying all the characteristics of lining cells in bone including
      expression of OPG and RANKL. Reduced bone turnover leads to a decrease in the
      number of BRCs, while increased turnover causes an increase in the number of
      BRCs. The secretion of regulatory factors inside a confined space separated from
      the bone marrow would facilitate local regulation of the remodeling process
      without interference from growth factors secreted by blood cells in the marrow
      space. The BRC also creates an environment where cells inside the structure are
      exposed to denuded bone, which may enable direct cellular interactions with
      integrins and other matrix factors known to regulate osteoclast/osteoblast
      activity. However, the denuded bone surface inside the BRC also constitutes an
      ideal environment for the seeding of bone metastases, known to have high affinity
      for bone matrix. Circulating osteoclast- and osteoblast precursor cells have been
      demonstrated in peripheral blood. The dominant pathway regulating osteoclast
      recruitment is the RANKL/OPG system, while many different factors (RUNX, Osterix)
      are involved in osteoblast differentiation. Both pathways are modulated by
      calcitropic hormones.

PMID- 21188537
TI  - Weight loss and changes in generic and weight-specific quality of life in obese
      adolescents.
AB  - PURPOSE: To investigate how weight loss correlates with changes in generic and
      weight-specific quality of life (QoL). METHODS: Youth generic (YQOL-S) and weight
      specific instruments (YQOL-W) from 133 youth age 11-19 were analyzed at the
      beginning and end of 4-week immersion camp sessions known to produce weight loss.
      Paired samples t tests were used to test mean difference between baseline and
      final Body Mass Index (BMI) and YQOL-S and YQOL-W scores. YQOL-S and YQOL-W
      scores were transformed to values between 0 and 100, with higher values
      indicating better QOL. Cohen's d effect sizes were calculated to assess magnitude
      of effects. Percent weight loss (as % of baseline weight), change in BMI
      (baseline kg/m2-follow-up kg/m2), and change in % overweight ((BMI-50th% BMI for
      age and sex)/50th% BMI for age and sex * 100) were calculated. Multiple
      regressions were used to model final YQOL scores in the 11-14 and 15-19 age
      groups as functions of each measure of weight change, sex, age, and baseline YQOL
      score. RESULTS: Youth experienced significant reductions in BMI (Mean change =
      3.7, SD = 1.4, t = 34.1, P < 0.001) and in the other measures of weight change.
      YQOL-S and YQOL-W scores improved significantly (P < 0.001), and effect sizes
      were 0.61 and 0.66, respectively. CONCLUSION: Changes in generic and weight
      specific quality of life scores are associated with weight loss. The weight
      specific measure is slightly more sensitive to weight changes; however, when
      controlling for modifiers, the YQOL-W remained significantly associated with
      weight loss, while the generic QoL measure did not.

PMID- 21188538
TI  - External validity of the pediatric cardiac quality of life inventory.
AB  - PURPOSE: The Pediatric Cardiac Quality of Life Inventory (PCQLI) is a disease
      specific, health-related quality of life (HRQOL) measure for pediatric heart
      disease (HD). The purpose of this study was to demonstrate the external validity
      of PCQLI scores. METHODS: The PCQLI development site (Development sample) and six
      geographically diverse centers in the United States (Composite sample) recruited
      pediatric patients with acquired or congenital HD. Item response option
      variability, scores [Total (TS); Disease Impact (DI) and Psychosocial Impact (PI)
      subscales], patterns of correlation, and internal consistency were compared
      between samples. RESULTS: A total of 3,128 patients and parent participants
      (1,113 Development; 2,015 Composite) were analyzed. Response option variability
      patterns of all items in both samples were acceptable. Inter-sample score
      comparisons revealed no differences. Median item-total (Development, 0.57;
      Composite, 0.59) and item-subscale (Development, DI 0.58, PI 0.59; Composite, DI
      0.58, PI 0.56) correlations were moderate. Subscale-subscale (0.79 for both
      samples) and subscale-total (Development, DI 0.95, PI 0.95; Composite, DI 0.95,
      PI 0.94) correlations and internal consistency (Development, TS 0.93, DI 0.90, PI
      0.84; Composite, TS 0.93, DI 0.89, PI 0.85) were high in both samples.
      CONCLUSION: PCQLI scores are externally valid across the US pediatric HD
      population and may be used for multi-center HRQOL studies.

PMID- 21188539
TI  - Case report: renal cell carcinoma segregating with a t(2;3)(q37.3;q13.2)
      chromosomal translocation in an Ashkenazi Jewish family.
AB  - Chromosome translocations involving chromosome 3 have previously been associated
      with the development of renal cell carcinoma. In this report we describe an
      Ashkenazi Jewish family with a previously unreported balanced constitutional
      translocation (t(2;3)(q37.3;q13.2)) segregating with the development of clear
      cell renal carcinomata in three family members spanning two generations. We
      outline the difficulties with the clinical utility of this finding for genetic
      counselling and risk management strategies. We suggest that an additional renal
      cancer susceptibility gene may exist at 3q13.2, and review known breakpoints in
      the autosomes which are associated with clear cell renal cell carcinoma.

PMID- 21188540
TI  - Heterogeneity of familial medulloblastoma and contribution of germline PTCH1 and
      SUFU mutations to sporadic medulloblastoma.
AB  - PTCH1 and SUFU are both regulators of the sonic hedgehog signalling pathway.
      Germline inactivating mutations in both genes are associated with multisystem
      phenotypes including medulloblastoma. Somatic inactivating mutations in PTCH1 and
      SUFU each occur in approximately 10% of medulloblastomas. Recently, SUFU
      mutations were reported in familial medulloblastoma pedigrees without additional
      phenotypic features. We sought to further investigate the contribution of
      germline PTCH1 and SUFU mutations to familial and sporadic medulloblastoma. We
      performed full-gene mutational analysis of both PTCH1 and SUFU in three familial
      medulloblastoma pedigrees and 83 individuals with sporadic non-familial
      medulloblastoma. We identified no mutations in PTCH1 or SUFU in the three
      familial medulloblastoma pedigrees. We identified no PTCH1 mutations and two SUFU
      mutations that cause premature protein truncating in the series of sporadic non
      familial medulloblastomas. The SUFU mutations were identified in two of the 16
      individuals with desmoplastic medulloblastomas. These data indicate that familial
      medulloblastoma is a genetically heterogeneous disorder with at least one further
      susceptibility gene to be discovered. Furthermore, although both PTCH1 and SUFU
      play a key role in the sonic hedgehog signalling pathway, PTCH1 does not make an
      appreciable contribution to non-familial sporadic medulloblastoma, whereas
      inactivating germline mutations of SUFU cause ~2-3% of sporadic medulloblastomas
      and > 10% of desmoplastic medulloblastomas.

PMID- 21188541
TI  - Epithelioid glioblastoma changed to typical glioblastoma: the methylation status
      of MGMT promoter and 5-ALA fluorescence.
AB  - A 55-year-old man was admitted to our hospital complaining of left hemiparesis.
      Magnetic resonance imaging (MRI) showed a smooth ring-like enhanced cystic tumor
      in the right parietal lobe. He underwent gross total resection of the tumor under
      neuronavigation and 5-aminolevulinic acid (5-ALA) fluorescence guiding method.
      Histopathological examination of the tumor showed small cells formed epithelioid
      solid nests with some focus of duct-like structure. On the basis of the MRI and
      operative and histological findings, this tumor was diagnosed as a metastatic
      poorly differentiated carcinoma, although the primary cancer could not be
      detected by metastatic work-ups. Afterward, this tumor recurred repeatedly.
      Histopathological examination of specimen from the fourth surgery indicated that
      the tumor was a glioblastoma (GBM). In the review of the histology and
      immunohistochemistry of the first tumor, atypical fibrillary cells were seen
      between solid nests and positive for glial fibrillary acidic protein, therefore
      the tumor was retrospectively diagnosed as epithelioid GBM. We assessed whether
      the changes in histopathology were accompanied by changes in the methylation
      status of O6-methylguanine methyltransferase (MGMT) promoter and the status of 5
      ALA fluorescence. The methylation status of the MGMT promoter was found to have
      changed from methylated to unmethylated and 5-ALA fluorescence became positive
      along with the histological change.

PMID- 21188542
TI  - Precise comparison of protoporphyrin IX fluorescence spectra with pathological
      results for brain tumor tissue identification.
AB  - Photodynamic diagnosis is used during glioma surgery. Although some studies have
      shown that the spectrum of fluorescence was efficient for precise tumor
      diagnosis, previous methods to characterize the spectrum have been problematic,
      which can lead to misdiagnosis. In this paper, we introduce a comparison
      technique to characterize spectrum from pathology and results of preliminary
      measurement using human brain tissues. We developed a spectrum scanning system
      that enables spectra measurement of raw tissues. Because tissue preparations
      retain the shape of the device holder, spectra can be compared precisely with
      pathological examination. As a preliminary analysis, we measured 13 sample
      tissues from five patients with brain tumors. The technique enabled us to measure
      spectra and compare them with pathological results. Some tissues exhibited a good
      relationship between spectra and pathological results. Although there were some
      false positive and false negative cases, false positive tissue had different
      spectra in which intensity of short-wavelength side was also high. The proposed
      technique provides an accurate comparison of quantitative fluorescence spectra
      with pathological results. We found that spectrum analysis may reduce false
      positive errors. These results will increase the accuracy of tumor tissue
      identification.

PMID- 21188543
TI  - A study of needle stick injuries among non-consultant hospital doctors in
      Ireland.
AB  - INTRODUCTION: NCHDs are exposed to a great number of blood-borne infections.
      Needle stick injuries are possibly the main route of acquiring such infections
      from a non-consultant hospital doctors (NCHDs) perspective. This study examines
      NCHDs experiences surrounding needle stick injuries. METHODS: A cross-sectional
      self-administered anonymous questionnaire survey was conducted on 185 NCHDs
      working in a clinical setting among seven teaching hospitals in Ireland. Implied
      consent was obtained. The data was analysed using Excel spreadsheets. Ethical
      approval was received. RESULTS: A response rate of 85.4% (158/185) was achieved.
      Findings of the study are shown in the manuscript table. CONCLUSIONS: A needle
      stick injury (NI) history is greater among surgical NCHDs than medical NCHDs. The
      level of disposable glove usage is worryingly poor. Training in sharps handling
      and dealing with a NI needs to be addressed. HIV is the blood-borne infection
      most fear of being contracting as a consequence of a NI.

PMID- 21188544
TI  - Alcohol use disorders after bariatric surgery.
AB  - BACKGROUND: The increased incidence of alcohol use disorders (AUD) after
      bariatric surgery has been proposed despite limited empirical support. We sought
      to determine the prevalence of current and lifetime AUD and other Axis I
      diagnoses in patients who have undergone bariatric surgery, and to test the
      hypothesis that greater weight loss is associated with a higher incidence of AUD
      following surgery. METHODS: Individuals who underwent bariatric surgery between
      2004 and 2007 were recruited for inclusion in the study. The diagnosis of current
      and lifetime AUD and other Axis I disorders was assessed using the Structured
      Clinical Interview for DSM-IV. RESULTS: A total of 51 individuals were included.
      The prevalence of lifetime and current AUD was 35.3% and 11.8%, respectively. No
      associations were found between weight loss following surgery and the development
      of an AUD or other Axis I diagnoses. Significantly more current AUD was reported
      in (1) individuals with a lifetime history of AUD compared to those without a
      lifetime AUD (p < 0.05), and (2) individuals undergoing Roux-en-Y gastric bypass
      (RYGB) compared to those undergoing the laparoscopic adjustable gastric banding
      (LAGB) surgery (p < 0.05). CONCLUSIONS: Individuals undergoing bariatric surgery
      were found to have a lifetime prevalence of AUD comparable to the general
      population. Although weight loss was not associated with the development of an
      AUD following surgery, individuals with a lifetime history of AUD may be at
      increased risk for relapsing to alcohol use after surgery. All instances of
      current AUD were identified in individuals undergoing RYGB as opposed to LAGB.

PMID- 21188545
TI  - Long-term results of a prospective study on laparoscopic adjustable gastric
      banding for morbid obesity.
AB  - BACKGROUND: The objective of this study was to study the long-term outcome of
      adjustable gastric banding in the treatment of morbid obesity. In Europe, the
      preference for gastric band has declined in favor of Roux-Y-gastric bypass.
      METHODS: This is a follow-up of a prospective study on a large cohort of patients
      after laparoscopic gastric banding (LAGB) for morbid obesity. RESULTS: Complete
      data were collected on 656 patients (88%) from a cohort of 745 patients. After a
      median follow-up of 95 months (range 60-155), the mean BMI dropped from 41.0 +/-
      7.3 to 33.2 +/- 7.1 kg/m2, with a 46.2 +/- 36.5% excess weight loss (EWL). A more
      than 50% EWL was achieved in 44% of patients. The band was still in place in
      77.1% of patients; conversion to gastric bypass after band removal was carried
      out in 98 (14.9%) patients, while a simple removal was done in only 52 (7.9%)
      patients. Band removal was more likely in women and patients with a higher BMI.
      CONCLUSIONS: After LAGB, band removal was necessary for complications or
      insufficient weight loss in 24% of patients. Nearly half of the patients achieved
      a more than 50% EWL, but in 88%, a more than 10% EWL was observed. LAGB can
      achieve an acceptable weight loss in some patients, but the failure in one out of
      four patients does not allow proposing it as a first-line option for the
      treatment of obesity.

PMID- 21188547
TI  - Nitrate as an oxidant in the cathode chamber of a microbial fuel cell for both
      power generation and nutrient removal purposes.
AB  - Nitrate ions were used as the oxidant in the cathode chamber of a microbial fuel
      cell (MFC) to generate electricity from organic compounds with simultaneous
      nitrate removal. The MFC using nitrate as oxidant could generate a voltage of 111
      mV (1,000 Omega) with a plain carbon cathode. The maximum power density achieved
      was 7.2 mW m(-2) with a 470 Omega resistor. Nitrate was reduced from an initial
      concentration of 49 to 25 mg (NO (3) (-) -N) L(-1) during 42-day operation. The
      daily removal rate was 0.57 mg (NO (3) (-) -N) L(-1) day(-1) with a voltage
      generation of 96 mV. In the presence of Pt catalyst dispersed on cathode, the
      cell voltage was significantly increased up to 450 mV and the power density was
      117.7 mW m(-2), which was 16 times higher than the value without Pt catalyst.
      Significant nitrate removal was also observed with a daily removal rate of 2 mg
      (NO (3) (-) -N) L(-1) day(-1), which was 3.5 times higher compared with the
      operation without catalyst. Nitrate was reduced to nitrite and ammonia in the
      liquid phase at a ratio of 0.6% and 51.8% of the total nitrate amount. These
      results suggest that nitrate can be successfully used as an oxidant for power
      generation without aeration and also nitrate removal from water in MFC. However,
      control of the process would be needed to reduce nitrate to only nitrogen gas,
      and avoid further reduction to ammonia.

PMID- 21188546
TI  - Evaluation of bone mineral density loss in morbidly obese women after gastric
      bypass: 3-year follow-up.
AB  - Studies that evaluate the influence of gastric bypass (RYGP) on bone mass are
      limited to short-term follow-up. We analysed changes in bone mineral density
      (BMD) three years after surgery and evaluated the main determinants of the
      development of bone disease. Prospective study of 59 morbidly obese white women
      aged 46 +/- 8 years. BMD scanning using DEXA and plasma determinations of
      calcium, parathyroid hormone, 25-hydroxyvitamin D and insulin-like growth factor
      I were made prior, at 12 months and 3 years after surgery. In the first
      postoperative year BMD decreased at femoral neck (FN) 10.2 % and in the lumbar
      spine (LS) 3.2 %, in the third year it additionally decreased 2.7 % and 3.1 %,
      respectively. BMD at both sites remained above the values of women of the same
      age. In the follow-up, 1.7 % developed osteoporosis at FN and 6.8 % at LS.
      Patients with bone disease were older, the percentage of women with menopause was
      greater in this group and had lower initial and final values of lean mass. The
      percentage of BMD loss at FN remained positively associated with the percentage
      of lean mass loss [beta 0.304, p=0.045], and menopause [beta 0.337, p=0.025].
      Major osteoporotic fracture and hip fracture risk was low even in menopausal
      patients (3.1 % and 0.40 %, respectively). After RYGP menopausal women and those
      with greater lean mass loss are at higher risk of BMD loss but progression to
      osteoporosis is uncommon and the risk of fracture is low.

PMID- 21188548
TI  - Bacillus spp. of human origin: a potential siderophoregenic probiotic bacteria.
AB  - Bacillus spp. ST13, isolated from human stool, was evaluated for siderophoregenic
      and probiotic qualities prior to its possible application for iron nutrition in
      humans and animals. It was tested for siderophore production in iron-limiting
      conditions and found to produce catecholate type of siderophore on the basis of
      high-performance liquid chromatography (HPLC), FT-IR, NMR, and mass spectra
      analysis. The isolate was screened for probiotic properties as per WHO and FAO
      guidelines. The strain ST13 can survive stomach acidity, bile salt and partially
      simulated gastrointestinal tract conditions. It was susceptible to most of the
      antibiotic tested and showed antimicrobial activity against enteric pathogens
      like Salmonella typhimurium, Streptococcus pyogenes, and Staphylococcus aureus.
      Strain ST13 showed close similarity with Bacillus subtilis using 16S r-RNA gene
      sequence analysis and biochemical characterization. The methanolic extract of
      ST13 siderophore was evaluated for DPPH radical scavenging activity, which showed
      94.55 +/- 0.9% of radical scavenging effect.

PMID- 21188550
TI  - Clones identification and genetic characterization of Garnacha grapevine by means
      of different PCR-derived marker systems.
AB  - This study uses PCR-derived marker systems to investigate the extent and
      distribution of genetic variability of 53 Garnacha accessions coming from Italy,
      France and Spain. The samples studied include 28 Italian accessions (named Tocai
      rosso in Vicenza area; Alicante in Sicily and Elba island; Gamay perugino in
      Perugia province; Cannonau in Sardinia), 19 Spanish accessions of different types
      (named Garnacha tinta, Garnacha blanca, Garnacha peluda, Garnacha roja, Garnacha
      erguida, Garnacha roya) and 6 French accessions (named Grenache and Grenache
      noir). In order to verify the varietal identity of the samples, analyses based on
      14 simple sequence repeat (SSR) loci were performed. The presence of an
      additional allele at ISV3 locus (151 bp) was found in four Tocai rosso accessions
      and in a Sardinian Cannonau clone, that are, incidentally, chimeras. In addition
      to microsatellite analysis, intravarietal variability study was performed using
      AFLP, SAMPL and M-AFLP molecular markers. AFLPs could discriminate among several
      Garnacha samples; SAMPLs allowed distinguishing few genotypes on the basis of
      their geographic origin, whereas M-AFLPs revealed plant-specific markers,
      differentiating all accessions. Italian samples showed the greatest variability
      among themselves, especially on the basis of their different provenance, while
      Spanish samples were the most similar, in spite of their morphological diversity.

PMID- 21188549
TI  - Enhanced angiotensin-converting enzyme 2 attenuates angiotensin II-induced
      collagen production via AT1 receptor-phosphoinositide 3-kinase-Akt pathway.
AB  - Recent reports support a protective role for angiotensin-converting enzyme 2
      (ACE2) against glomerular diseases, especially by decreasing of extracellular
      matrix (ECM) proteins. However, the mechanism regulating this effect appears to
      be complex and poorly understood. Our aim was to investigate whether or not ACE2
      ameliorates the profibrotic effects of Ang II-mediated, Akt-dependent pathways in
      the mouse mesangial cell line, MES-13.Gene transfer of ACE2 suppressed Ang II
      activated Akt-phosphorylation, accompanied by a decreased level of collagen type
      I in cells. In addition, Ang II-induced collagen type I synthesis in MES-13s by
      activating the Ang II/AT-1R-PI3K pathway. This transactivation was dependent on
      cAMP/Epac but not on PKA. TGF-betaRI played a pivotal role in this signaling
      pathway inducing collagen deposition effects which could be reversed by ACE2 gene
      transfer in MES-13 cells. The results revealed that gene transfer of ACE2
      regulated Ang II-mediated AT1R-TGFbetaRI-PI3K-Akt signaling and involved the
      synthesis of collagen. The beneficial effect of ACE2 overexpression appeared to
      result mainly from blocking phosphorylation of Akt in mesangial cells, suggesting
      that the ACE2 gene might be a novel therapeutic target for glomerular diseases.

PMID- 21188551
TI  - The urgent need for new diagnostics for symptomatic tuberculosis in children.
AB  - TB is a major public health problem causing 9 million cases, of which 10%-15%
      occur in children each year. Historically, children have received lower priority
      within TB control activities because they are considered less infectious than
      smear-positive adults. This review argues that TB is a public health problem in
      children and that poor awareness of the magnitude of the problem emanates from
      the lack of suitable pediatric diagnostic tests for TB and the characteristics of
      the disease in young children. New TB diagnostics, approved for use in adults
      have not been evaluated in children, although there is limited evidence that some
      of these tests hold promise and should be assessed. There are several approaches
      that could be used to improve the performance of tests in pediatric patients.
      These include improved methods for specimen collection and processing. The value
      of collecting specimens from multiple anatomical sites to shorten the diagnostic
      process and improve sensitivity was reported recently and the combination of
      expectorated sputum, nasopharyngeal aspirate, induce sputum and gastric aspirate
      may result in a similar yield than specimens collected over consecutive days.
      Methods for sample collection such as fine needle aspiration biopsy should be
      used more frequently and the Microscopic Observation Drug Sensitivity (MODS)
      assay has higher sensitivity than LJ culture. There is however very scanty
      evidence of the performance of other promising tests such as the fully automated
      NAAT (Xpert) and Line Probe Assays and loop mediated isothermal amplification.
      Although the future holds promise, increased support from international
      organizations and funding agencies is needed to promote the evaluation and
      development of new diagnostics that are suitable for TB in children.

PMID- 21188552
TI  - A case of classical galactosemia: identification and characterization of 3
      distinct mutations in galactose-1-phosphate uridyl transferase (GALT) gene in a
      single family.
AB  - Galactosemia is an autosomal recessive disorder of galactose metabolism. In the
      very first instance of its kind from India, the authors report the presence of
      three different galatose-1-phosphate uridyl transferase (GALT) gene mutations,
      associated with galactosemia, in a single Indian family. One of the three
      mutations, S307X, is a novel mutation (GenBank Accession number GQ355273) and is
      of nonsense nature causing the truncation of the GALT protein resulting in the
      decreased enzyme activity. The authors have also emphasized the importance of
      introduction of new born screening program for galactosemia and its genetic
      analysis in select settings across the country.

PMID- 21188553
TI  - Idiopathic myelofibrosis in an infant.
AB  - Idiopathic Myelofibrosis (MF) is an extremely rare condition in children. It has
      a very variable clinical spectrum. Cases of secondary myelofibrosis associated
      with Vitamin D deficiency and Systemic Lupus Erythematosus have been reported
      from India .In this case report, the authors describe clinical signs, laboratory
      findings and histologic features in a 6 month old infant with Idiopathic
      myelofibrosis.

PMID- 21188554
TI  - Gorham-Stout syndrome with chylothorax in a six-year-old boy.
AB  - Gorham-Stout syndrome, also called "disappearing bone disease, diffuse cystic
      angiomatosis of bone, disseminated lymphangiomatosis, Gorham's vanishing bone
      disease, phantom bone disease or idiopathic massive osteolysis, is a rare disease
      of unknown etiology and pathogenesis. It is characterized by rapidly progressive
      localized massive osteolysis associated with proliferation of vascular structures
      of benign origin in which the absence of new bone formation is representative.
      When it is complicated by chylothorax, the prognosis is poor. The authors report
      a 6-year-old boy with Gorham-Stout syndrome who presented with pleural effusion
      showing features of chylothorax, who responsed poorly to currently available
      therapeutic modalities.

PMID- 21188555
TI  - Coreceptors and HIV-1 pathogenesis.
AB  - The major HIV-1 coreceptors, CCR5 and CXCR4, mediate virus entry into CD4+ cells
      and are therefore a critical component of the HIV-1 life cycle. Alterations in
      coreceptor preference as well as the efficiency and mechanism of interaction
      between HIV-1 and CCR5 and/or CXCR4 has a significant influence on viral tropism,
      progression of disease, and response to coreceptor antagonists. In addition,
      these alterations influence the susceptibility of CD4+ T-cell, monocyte, and
      dendritic cell subsets to infection and therefore, are important for several
      facets of HIV-1 pathogenesis including the establishment of latent reservoirs,
      trafficking, and transmission. This review highlights recent literature that has
      advanced our understanding of the role of coreceptors in HIV-1 pathogenesis.

PMID- 21188556
TI  - Revisiting immune exhaustion during HIV infection.
AB  - Chronic immune activation is a hallmark of HIV infection, yet the underlying
      triggers of immune activation remain unclear. Persistent antigenic stimulation
      during HIV infection may also lead to immune exhaustion, a phenomenon in which
      effector T cells become dysfunctional and lose effector functions and
      proliferative capacity. Several markers of immune exhaustion, such as PD-1, LAG
      3, Tim-3, and CTLA-4, which are also negative regulators of immune activation,
      are preferentially upregulated on T cells during HIV infection. It is not yet
      clear whether accumulation of T cells expressing activation inhibitory molecules
      is a consequence of general immune or chronic HIV-specific immune activation.
      Importantly, however, in vitro blockade of PD-1 and Tim-3 restores HIV-specific T
      cell responses, indicating potential for immunotherapies. In this review we
      discuss the evolution of our understanding of immune exhaustion during HIV
      infection, highlighting novel markers and potential therapeutic targets.

PMID- 21188558
TI  - Survival advantage in CLL with frontline FCR therapy.

PMID- 21188557
TI  - Therapies targeting exogenous cholesterol uptake: new insights and controversies.
AB  - Exogenous cholesterol uptake involves a complex process in the intestines for the
      absorption of cholesterol and bile acids. This process is regulated by intestinal
      nuclear transcription factors such as LXR that affect sterol transporters NPC1L1,
      ABCG5/G8, and ABCG1, and enzymes such as ACAT-2. Plant sterol/stanols, ezetimibe,
      and bile acid sequestrants have a variety of effects on these various
      transporters, and new insights into their mechanism(s) of action have provided a
      plethora of exciting targets for metabolic diseases, dyslipidemia, and
      atherosclerosis.

PMID- 21188559
TI  - 1H, 13C and 15N resonances of the AlgE62 subunit from Azotobacter vinelandii
      mannuronan C5-epimerase.
AB  - The 17.7 kDa R2 module from Azotobacter vinelandii mannronan C5-epimerase AlgE6
      has been isotopically labeled ((13)C,(15)N) and recombinantly expressed. Here we
      report the (1)H, (13)C, (15)N resonance assignment of AlgE6R2.

PMID- 21188560
TI  - Backbone 1H, 15N, and 13C resonance assignments for the NOXO1beta PX domain.
AB  - NOXO1 (Nox Organizer 1) is a homolog of the NAPDH oxidase protein p47(phox).
      NADPH oxidases transfer electrons from NADPH to molecular oxygen, generating the
      superoxide anion. NOXO1 contains an N-terminal PX (phox homology) domain and is
      one of several PX domain-containing proteins found in the cytosolic subunits of
      the NADPH oxidase complex. These PX domains bind to membrane lipids and target
      the protein to membranes, recruiting other cytosolic components to the membrane
      bound components and aiding formation of a active enzyme complex. This
      recruitment represents a level of regulation of these oxidases. Here we report
      the backbone assignments of NOXO1beta PX.

PMID- 21188561
TI  - 1H, 13C and 15N assignment of the GNA1946 outer membrane lipoprotein from
      Neisseria meningitidis.
AB  - GNA1946 (Genome-derived Neisseria Antigen 1946) is a highly conserved exposed
      outer membrane lipoprotein from Neisseria meningitidis bacteria of 287 amino acid
      length (31 kDa). Although the structure of NMB1946 has been solved recently by X
      Ray crystallography, understanding the behaviour of GNA1946 in aqueuos solution
      is highly relevant for the discovery of the antigenic determinants of the protein
      that will possibly lead to a more efficient vaccine development against virulent
      serogroup B strain of N. meningitidis. Here we report almost complete (1)H, (13)C
      and (15)N resonance assignments of GNA1946 (residues 10-287) in aqueous buffer
      solution.

PMID- 21188562
TI  - Effects of dairy intake on hyperuricemia and gout.
AB  - Dietary modification is frequently recommended for patients with gout.
      Longitudinal observational studies have shown a clear inverse relationship
      between low-fat dairy intake and gout risk. Several checkpoints in gout
      pathogenesis may be targeted by dairy intake. Cross-sectional and short-term
      intervention studies of healthy volunteers have demonstrated that low-fat dairy
      intake has a moderate urate-lowering effect. In addition, certain dairy
      fractions, particularly glyco-macropeptide and G600 milk fat extract, have anti
      inflammatory properties in experimental models of acute gout. Such anti
      inflammatory properties may contribute to the reduction in gout risk through
      inhibition of the inflammatory response to monosodium urate crystals within the
      joint. Well-controlled intervention studies in patients with gout are now needed
      to determine the clinical relevance of these observations in order to guide
      dietary recommendations for this disease.

PMID- 21188563
TI  - Low-dose rituximab combined with short-term glucocorticoids up-regulates Treg
      cell levels in patients with immune thrombocytopenia.
AB  - This randomized trial was performed to investigate the efficacy of low-dose
      rituximab in combination with glucocorticoids for treatment of patients with
      immune thrombocytopenia (ITP). Sixty-two patients were randomly separated into
      the glucocorticoids (control) and the experimental (glucocorticoids + rituximab)
      groups. Patients in both groups received dexamethasone 40 mg/day on days 1-4,
      followed by decrements of prednisone 60, 30, 15, 10 mg/day on days 5-7, 8-14, 15
      21, 22-28, respectively. Patients in the experimental group also received
      rituximab 100 mg on days 7, 14, 21, 28. The overall response (OR) was similar in
      both groups at day 28 (experimental group vs. glucocorticoids group: 80.6 vs.
      74.2%, P = .938); however, sustained response (SR) was more pronounced in the
      experimental group as compared to that in the glucocorticoids group (77.4 vs.
      38.7%, P < .001). Both groups showed similar incidence of adverse events
      (experimental group vs. glucocorticoids group: 9.7 vs. 6.5%, P = .325). As
      expected, B cell depletion was seen in the experimental group. In addition, both
      groups experienced a significant up-regulation in Treg cell levels, but the up
      regulation in the experimental group was maintained at an even higher level and
      persisted a longer time than those in the glucocorticoids group. Thus, low-dose
      rituximab combined with short-term glucocorticoids provides an alternative
      treatment for ITP prior to splenectomy.

PMID- 21188564
TI  - CD16 antigen is a positive marker of peripheral blood-derived early endothelial
      progenitor cells.

PMID- 21188565
TI  - Oncoplastic surgery in a Japanese patient with breast cancer in the lower inner
      quadrant area: partial mastectomy using horizontal reduction mammoplasty.
AB  - We report the results of oncoplastic surgery in a Japanese patient with early
      breast cancer. Her breasts were ptotic, and her lesion was considered to be
      suitable for breast-conserving surgery. Oncoplastic surgery involving partial
      resection of the gland and a horizontal-type mammoplasty was performed. The
      technique was easy to perform, and the cosmetic outcome was excellent. 

PMID- 21188566
TI  - Effects of fasting on hypoxic ventilatory responses and the contribution of
      histamine H1 receptors in mice.
AB  - We tested the hypothesis that fasting affects hypoxic ventilatory responses
      through metabolic changes via histamine H1 receptors. Wild-type (WT) and
      histamine H1 receptor knockout (H1RKO) mice were studied in fed and fasted
      states. In the fed WT, hypoxic-gas exposure elicited an increase and a subsequent
      decline in ventilation (hypoxic ventilatory decline or HVD). HVD was influenced
      by fasting in breathing pattern with metabolic rate. Fasting elicited
      hypoglycemia, a drop in R, and increases in free fatty acid and ketone bodies in
      the serum. In H1RKO, HVD was blunted in the fed state, but it appeared in the
      fasted state. There was a minimal drop in R following fasting and a low
      triglyceride concentration. Thus, fasting affects HVD through a change in energy
      mobilization from glucose to lipid metabolism. Histamine H1 receptors are
      involved in HVD during fed and fasted states, resulting in adaptation to the
      environmental conditions.

PMID- 21188567
TI  - Image. Annular pancreas.

PMID- 21188568
TI  - [Study of lesional aspects of hydatid echinococcosis in man in Mauritania:
      fertility, histology of hydatid cysts and protoscolex viability].
AB  - A lesional study on human hydatidosis (localization, fertility of cysts,
      protoscolex viability, and histological structure) focused on 63 human hydatid
      cysts from patients operated at CHN of Nouakchott was conducted during the period
      1997-2007. The authors report the following results: the annual surgical
      incidence rate was in the order of 1.2% per 100,000 inhabitants. The lung was the
      primary localization of cyst (52%) followed by the liver (33%), spleen (4%),
      brain (3%), heart (2%), breasts (2%), kidney (2%), diaphragm (1%), and peritoneum
      (1%). The pulmonary cysts were larger and more fertile (76%) with protoscoleces
      also more viable (70%) compared with liver cysts (67-62%). The histology of
      hydatid cysts revealed in most cases a histological structure consistent with
      that described in the literature: thick cuticle, membrane proligeous, and
      capsules visible.

PMID- 21188569
TI  - Differential expression pattern of estrogen receptors, aromatase, and
      sulfotransferase in breast cancer tissue and corresponding lymph node metastases.
AB  - Patients with hormone receptor positive breast cancer who are treated with
      endocrine therapy generally have a good prognosis. However, resistance to
      hormonal therapy and progression occurs, and the reasons for this are manifold.
      It has been proposed that the local estrogenic environment has a role in the
      process of local invasion and progression. We have determined the expression
      pattern of estrogen receptor alpha, estrogen receptor beta, and the epithelial
      and stromal expression of the estrogen-metabolizing enzymes aromatase and
      sulfotransferase by immunohistochemistry in tissue arrays, containing 50 paraffin
      embedded sets of tissues obtained from breast cancer and from corresponding
      metastatic axillary lymph nodes of the same patients. We have found statistically
      significant higher estrogen receptors alpha and beta expression in primary tumors
      than in corresponding lymph node metastases (p = 0.0004 and p = 0.003,
      respectively). Aromatase was also expressed more frequently in epithelial as well
      as in stromal cells of the malignant tumor when compared to according lymph node
      metastases (p = 0.08 and p = 0.12, respectively). While in lymph node metastases
      only estrogen receptor alpha and stromal aromatase expression were correlated (p
      = 0.01), significant associations were seen between the estrogen receptor beta
      and sromal aromatase, and epithelial sulfotransferase (p = 0.0006 and p = 0.03,
      respectively) in the primary tumor. We hypothesize that the decreased expression
      of local estrogens by aromatase, in combination with a decreased expression of
      estrogen receptors alpha and beta in lymphatic metastases, renders these
      metastases hormone insensitive and could contribute to the poor response to
      endocrine therapy that is often seen in nodal-positive tumors.

PMID- 21188570
TI  - A percolation-like model for simulating inter-cellular diffusion in the context
      of bystander signalling in tumour.
AB  - Despite ongoing active research, the role of the radiation bystander effect in
      modifying local tissue response to an ionising radiation dose remains unclear.
      The present study aims to provide new insight by simulating the diffusion
      mediated inter-cellular communication processes in 2D and 3D cell-like structures
      to calculate likely signal ranges in the diffusion limited case. Random walks of
      individual signalling molecules were tracked between cells with inclusion of
      molecule-receptor interactions. The resulting diffusion anomaly is a function of
      cell density, signal uptake probability and the spatial arrangement of cells
      local to the signal origin. Uptake probability effects dominate percolation
      effects in disordered media. Diffusion through 2D structures is more conducive to
      anomalous diffusion than diffusion through 3D structures. Values for time
      dependent diffusion constants and permeability are derived for typical simulation
      parameters. Even at low signal uptake probabilities the communication range is
      restricted to a mean value of less than 100 MUm owing to complete signal uptake
      by 600 s. This should be considered in light of the potential influence of signal
      relaying, flow-dynamics or vasculature-mediated signalling.

PMID- 21188573
TI  - Assembly of polymer/lipid composite films on solids based on hairy rod LB-films.
AB  - The present work deals with the assembly of multilayers or rod-like polymers with
      hydrophobic side chains (called hairy rods) and their potential application as
      ultrathin polymer cushions for the build-up of self healing supported membranes
      on various solids (Si/SiO(2)-wafer, gold covered substrates). Three types of
      hairy rods were studied: Isopentyl cellulose (IPC), phtalocyaniatopolysiloxane
      with mixed alkane side chains (PCPS) and trimethylsilane cellulose (TMCS).
      Detailed analysis of the thickness of supported multilayers as a function of the
      number of deposited monolayers with ellipsometry, near infrared surface plasmon
      resonance (NIR-SPR), a quartz crystal microbalance (QCM) and reflection
      interference contrast microscopy (RICM), show that the basic building blocks of
      hairy rod multilayers are bilayers with the hydrophobic surfaces of the
      monolayers facing each other. Continuous and stable firms of hairy rods can be
      deposited if the hydrophobicities of the solid surface and the monolayer are
      matched. It is demonstrated by lateral diffusion measurements (using
      photobleaching techniques) that continuous phospholipid bilayers can be deposited
      onto multilayers of rigid rods of TMCS after hydrophilization by cleavage of
      trimethylsilane side chains in HCl-vapour, while stable lipid monolayers can be
      deposited onto hydrophobic surfaces of rigid rod layers. NIR-SPR allows the
      observation of double band reflectivity curves at interfaces separating different
      surface layers and thus offers the possibility of differential detection of
      ligand binding at the interface of differently functionalized domains.

PMID- 21188574
TI  - Modulation of lipid phase behavior by kosmotropic and chaotropic solutes :
      Experiment and thermodynamic theory.
AB  - By means of differential scanning calorimetry and from a review of published data
      we demonstrate in this work that low-molecular weight kosmotropic substances
      (water-structure makers) of different chemical structure such as disaccharides,
      proline, and glycerol have identical effects on the phase behavior of several
      kinds of phospholipids and glycolipids. These substances favor formation of the
      high-temperature inverted hexagonal phase (H(II)) and the low-temperature
      lamellar crystalline (L(c)) and gel (L( beta )) phases at the expense of the
      intermediate lamellar liquid-crystalline phase (L( alpha )). The latter phase may
      completely disappear from the phase diagram at high enough solute concentration.
      By contrast, chaotropic substances (water-structure breakers) such as sodium
      thiocyanate and guanidine hydrochloride expand the existence range of L( alpha )
      at the expense of the adjacent L( beta ) and H(II) phases. Moreover, chaotropes
      are able to induce the appearance of missing intermediate liquid-crystalline
      phases in lipids displaying direct L( beta )->H(II) transitions in pure water. In
      previous publications we have considered the influence of chaotropic and
      kosmotropic substances on the lipid phase behavior as a manifestation of their
      indirect (Hofmeister) interactions with the lipid aggregates. For a quantitative
      characterization of this effect, here we derive a general thermodynamic equation
      between lipid phase transition temperature and solute concentration, analogous to
      the Clapeyron-Clausius equation between transition temperature and pressure. It
      provides a clear description in physical quantities of the disparate effects of
      kosmotropic and chaotropic substances on the relative stability of the lipid
      water phases. According to this equation, the magnitude of the solute effect is
      proportional to the hydration difference of the adjacent lipid phases and
      inversely proportional to the transition latent heat. The sign and magnitude of
      the transition shifts depend also on the degree of solute depletion (for
      kosmotropes) or enrichment (for chaotropes) at the interfaces, in comparison to
      the solute concentration in bulk water.

PMID- 21188575
TI  - The effect of cholesterol in small amounts on lipid-bilayer softness in the
      region of the main phase transition.
AB  - The temperature dependence of the small-angle neutron scattering from aqueous
      multilammellar DMPC lipid bilayers, containing small amounts of cholesterol, is
      analyzed near the main phase transition by means of a simple geometric model
      which yields the lamellar repeat distance, the hydrophobic thickness of the
      bilayer, the interlamellar aqueous spacing, as well as fluctuation parameters.
      The observation of anomalous swelling behavior in the transition region is
      interpreted as an indication of bilayer softening and thermally reduced bending
      rigidity. Our results indicate that the effect of small amounts of cholesterol,
      ?3 mole%, is a softening of the bilayers in the transition region, whereas
      cholesterol contents above this range lead to the well-known effect of
      rigidification. The possible biological relevance of this result is discussed.

PMID- 21188576
TI  - The 7th Innsbruck Winter Symposium for Coagulation. Innsbruck, Austria. November
      5-6, 2010. "Haemostasis in massive bleeding and trauma".

PMID- 21188578
TI  - Novel methodology for the extraction and identification of natural dyestuffs in
      historical textiles by HPLC-UV-Vis-ESI MS. Case study: chasubles from the Wawel
      Cathedral collection.
AB  - High-performance liquid chromatography coupled with spectrophotometric and
      electrospray mass spectrometric detection (HPLC-UV-Vis-ESI MS) was used for
      characterization of natural dyes present in historical art works. The gradient
      program was developed for identification of 29 colorants of various polarities.
      Dual detection system (UV-Vis and ESI MS) allowed differentiation of all
      compounds, even if they were not completely separated. This enabled examination
      of more color compounds over a substantially shorter time in comparison with
      previously recommended methods. Moreover, for extraction of colorants from
      historical textiles a two-step sequential procedure was proposed, excluding
      evaporation used in earlier procedures. The developed method was successfully
      applied to identification of indigotin, carminic, kermesic, flavokermesic, dcII,
      dcIV, dcVII, and ellagic acids as well as luteolin, apigenin, and genistein in
      red, violet, and green fibers taken from three selected historical chasubles
      which belong to the collection of the Wawel Cathedral treasury (Cracow, Poland).
      Italian textiles from the fifteenth and sixteenth centuries, of which chasubles
      were made, were dyed with a limited number of dyestuffs, consistently used for
      all batches of fabrics. The obtained results also allowed confirmation of the
      structure of the so-called "dcII" component of cochineal as a C-glucose
      derivative of flavokermesic acid.

PMID- 21188579
TI  - Rapid determination of urinary di(2-ethylhexyl) phthalate metabolites based on
      liquid chromatography/tandem mass spectrometry as a marker for blood transfusion
      in sports drug testing.
AB  - Methods of blood doping such as autologous and homologous blood transfusion are
      one of the main challenging doping practices in competitive sport. Whereas
      homologous blood transfusion is detectable via minor blood antigens, the
      detection of autologous blood transfusion is still not feasible. A promising
      approach to indicate homologous or autologous blood transfusion is the
      quantification of increased urinary levels of di(2-ethylhexyl) phthalate (DEHP)
      metabolites found after blood transfusion. The commonly used plasticizer for
      flexible PVC products, such as blood bags, is DEHP which is known to diffuse into
      the stored blood. Therefore, a straight forward, rapid and reliable assay is
      presented for the quantification of the main metabolites mono(2-ethyl-5-oxohexyl)
      phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate and mono(2-ethylhexyl)
      phthalate that can easily be implemented into existing multi-target methods used
      for sports drug testing. Quantification of the DEHP metabolites was accomplished
      after enzymatic hydrolysis of urinary glucuronide conjugates and direct injection
      using isotope-dilution liquid chromatography/tandem mass spectrometry. The method
      was fully validated for quantitative purposes considering the parameters
      specificity, linearity (1-250 ng/mL), inter- (2.4%-4.3%) and intra-day precision
      (0.7%-6.1%), accuracy (85%-105%), limit of detection (0.2-0.3 ng/mL), limit of
      quantification (1 ng/mL), stability and ion suppression effects. Urinary DEHP
      metabolites were measured in a control group without special exposure to DEHP (n
      = 100), in hospitalized patients receiving blood transfusion (n = 10), and in
      athletes (n = 468) being subject of routine doping controls. The investigation
      demonstrates that significantly increased levels of secondary DEHP metabolites
      were found in urine samples of transfused patients, strongly indicating blood
      transfusion.

PMID- 21188580
TI  - Evaluation of new ionic liquids as high stability selective stationary phases in
      gas chromatography.
AB  - Two ionic liquids (ILs), namely (S,S)-1-butyl-3-(2'-hydroxy-cyclohexyl)-3H
      imidazol-1-ium tetrafluoroborate and (S,S)-1-butyl-3-(2'-acetyl-cyclohexyl)-3H
      imidazol-1-ium tetrafluoroborate have been employed as stationary phases in
      capillary gas chromatography. These new phases exhibit a column efficiency of
      1,600 and 2,100 plates m(-1) for IL 1 and IL 2, respectively, a wide operating
      temperature range and good thermal stability (bleeding temperature of 250 
      degrees C for IL 1 and 160  degrees C for IL 2). Inverse gas chromatography (GC)
      analyses were used to study the solvation properties of these ILs through a
      linear solvation energy model. The application of these ILs as new GC stationary
      phases was studied. These stationary phases exhibited unique selectivity for many
      organic substances, such as alkanes, ketones, esters, and aromatic compounds. The
      efficient separation of several mixtures containing compounds of different
      polarities and the good separation of fatty acid methyl esters (FAMEs) and
      cis/trans isomers indicate that these ILs may be applicable as a new type of GC
      stationary phases.

PMID- 21188581
TI  - Trends in analytical atomic and molecular mass spectrometry in biology and the
      life sciences.
AB  - Trends in analytical atomic and molecular mass spectrometry (MS) are reviewed
      here with an emphasis on problems related to biology and the life sciences. The
      move towards novel desorption/ionization techniques including matrix-free laser
      desorption-ionization MS and recent technological developments in MS imaging of
      elements, small molecules, and proteins are discussed. Recent developments in the
      interfacing of microfluidics with MS are also reviewed. Metabolic profiling,
      evaluation of biomarkers, pharmaceutical metabolite identification, and many
      related topics are addressed.

PMID- 21188582
TI  - Mass spectrometry as test bench for medicinal chemistry studies.
AB  - This review describes how mass spectrometry can be used as a powerful test bench
      to obtain information on the biological activity of target compounds. Considering
      that mass spectrometry is based on the chemical reactivity of the analytes, it is
      possible to investigate the stability of the active compounds, to predict their
      behaviour in the environment of interest, and to obtain structure-reactivity
      relationships for new molecules of pharmacological interest. Electron ionization
      and metastable ion studies give evidence of the correlation between the mutagenic
      properties of a series of aryl and heteroaryl triazenes and mass spectrometric
      data. A linear relationship between the energetics of C(O)-O bond cleavage of
      some carbamic acid O-aryl esters and their FAAH inhibition activity has been
      proved by electrospray-ionization ion-trap mass spectrometry. An inverse
      correlation between the stability and cytotoxic activity of some copper complexes
      has been clearly established by electrospray-ionization mass spectrometry.
      Moreover, because of the sensitivity and specificity of mass spectrometry, it has
      been possible to determine and characterize impurities that in some cases can be
      the real bioactive compound.

PMID- 21188583
TI  - The giant calculus within the prostatic urethra.
AB  - The giant calculus within the prostatic urethra is a rare clinical entity in the
      young population. Most of the calculi within the urethra migrate from the urinary
      bladder and obliterate the urethra. These stones are often composed of calcium
      phosphate or calcium oxalate. The decision of treatment strategy is affected by
      the size, shape and position of the calculus and by the status of the urethra. If
      the stone is large and immovable, it may be extracted via the perineal or the
      suprapubic approach. In most cases, the giant calculi were extracted via the
      transvesical approach and external urethrotomy. Our case is the biggest prostatic
      calculus, known in the literature so far, which was treated endoscopically by the
      combination of laser and the pneumatic lithotriptor.

PMID- 21188584
TI  - A peptidoglycan monomer with the glutamine to serine change and basic peptides
      bind in silico to TLR-2 (403-455).
AB  - Bacterial cell wall polysaccharides, such as PGN, bind and activate TLR-2, NOD2
      and PGRP on monocytes/macrophages and activate inflammation. We found that the
      peptides containing basic amino acids (cations) at N -terminus and tyrosine at C
      terminus interfered with activating ability of PGN. This finding is significant
      because the ECD of TLR-2 in vivo encounters a large number of proteins or
      peptides. Some should bind ECD and "pre-form" TLR-2 to respond or not to its
      activators, although they cannot activate TLR-2 alone. TLR-2 is receptor for a
      large number of ligands, including lipopeptides and bacterial cell wall
      glycoproteins. A binding site for lipopeptides has been identified; however, a
      binding site for soluble or multimeric PGN has not been proposed. To identify the
      candidate binding sites of peptides and PGN on TLR-2, we modeled docking of
      peptides and of the PGN monomer (PGN-S-monomer) to extracellular domain (ECD-TLR
      2) of the unbound TLR-2. Quantification, in silico, of free energy of binding
      (DG) identified 2 close sites for peptides and PGN. The PGN-S-monomer binding
      site is between amino acids TLR-2, 404-430 or more closely TLR-2, 417-428. The
      peptide-binding site is between amino acids TLR-2, 434-455. Molecular models show
      PGN-S-monomer inserts its N -acetyl-glucosamine (NAG) deep in the TLR-2 coil,
      while its terminal lysine interacts with inside (Glu(403)) and outside pocket
      (Tyr(378)). Peptides insert their two N -terminal arginines or their C-terminal
      tyrosines in the TLR-2 coil. PGN did not bind the lipopeptide-binding site in the
      TLR-2. It can bind the C-terminus, 572-586 (DG = 0.026 kcal), of "lipopeptide
      bound" TLR-2. An additional, low-affinity PGN-binding site is TLR-2 (227-237).
      MTP, MDP, and lysine-less PGN bind to TLR-2, 87-113. This is the first report
      identifying candidate binding sites of monomer PGN and peptides on TLR-2.
      Experimental verification of our findings is needed to create synthetic adjuvant
      for vaccines. Such synthetic PGN can direct both adjuvant and cancer antigen to
      TLR-2.

PMID- 21188585
TI  - Physical and biological properties of homophilic therapeutic antibodies.
AB  - Homophilic antibodies have been discovered in mice and primates and can also be
      engineered. Compared to conventional antibodies, homophilic antibodies form
      lattices on targets leading to enhanced binding via polyvalent attachment.
      Previously, we have observed a paradoxical dose/potency effect with an engineered
      homophilic antibody against a human lung cancer tumor. Here, we have investigated
      some biophysical properties of homophilic antibodies and also studied the
      inhibition of human tumor growth in a xenograft model using homophilic Herceptin.
      Dimerization and viscosity of two homophilic antibodies are greater at
      physiological temperature than at 4 degrees C. Similarly, binding to solid-phase
      antigen is greater at 37 degrees C than at room temperature or 4 degrees C. Dimer
      formation is higher at therapeutic concentration, supporting the notion that
      preformed dimers in solution are the effective molecular species responsible for
      polyvalent target binding and enhanced therapeutic potency.

PMID- 21188586
TI  - Chemical composition and antibacterial potential of Artemisia arborescens L.
      essential oil.
AB  - This study was undertaken to characterize the essential oil (EO) of Artemisia
      arborescens growing wild in Sicily. EO, extracted by steam distillation, was
      examined for its chemical composition and for its capability to inhibit some food
      borne pathogen bacteria. A total of 43 compounds (13 monoterpene hydrocarbons, 14
      oxygenated monoterpenes, 10 sesquiterpene hydrocarbons, three oxygenated
      sesquiterpenes and less amount of other three compounds), which account 93.73% of
      the total oil, were identified by gas chromatography and gas chromatography-mass
      spectrometry. Oxygenated monoterpenes (57.32%) constituted the main fraction,
      with beta-thujone as the main compound (45.04%), followed by the sesquiterpene
      hydrocarbon chamazulene (22.71%). Undiluted EO showed a large inhibition spectrum
      against strains of Listeria monocytogenes (34 out of 44), whilst it was
      ineffective against enterobacteria and salmonellas. The minimum inhibition
      concentration (MIC) was evaluated for the two most sensitive strains (L.
      monocytogenes 186 and 7BO) at two cellular concentrations (10(6) and 10(7) CFU
      ml(-1)). The lowest MIC (0.625 MUl ml(-1), dilution of oil with acetone) was
      found for strain L. monocytogenes 186 at 10(6) CFU ml(-1).

PMID- 21188587
TI  - Studies of dimethylglycine oxidase isoenzymes in Arthrobacter globiformis cells.
AB  - Glycine betaine (GB) could be used by Arthrobacter globiformis cells as a sole
      carbon source. The cells took up this molecule in the low as well as in the high
      salinity medium. Addition of GB to the mineral medium with high salt
      concentration revealed that GB was also used as an osmoprotectant.
      Dimethylglycine oxidase (DMGO) was involved in the catabolism of GB. Two genes
      for DMGO were detected in a cloned 26267 bp fragment of A. globiformis DNA. The
      genes involved in the tetrahydrofolate-dependent assimilation of methyl groups
      were located nearby the two of DMGO genes. Both cloned A. globiformis DMGO were
      active. The activity of DMGO was detected in A. globiformis cells and it depended
      on the addition of GB and the salinity of the medium. Reverse transcription-PCR
      demonstrated that the addition of GB influenced the transcription of dmg genes.

PMID- 21188588
TI  - Counteractive action of nitric oxide on the decrease of nitrogenase activity
      induced by enhanced ultraviolet-B radiation in cyanobacterium.
AB  - The experimental enhancement of UV-B radiation resulted in damage to chlorophyll
      a in Spirulina platensis 794, and the degree of this damage was modified by
      chemical treatments. The addition of 0.5 mM sodium nitroprusside (SNP), a donor
      of nitric oxide (NO), to cultures of Spirulina platensis 794 could markedly
      alleviate the damage to chlorophyll-a caused by enhanced ultraviolet-B radiation.
      Exposure of N(2)-fixing cyanobacterium Spirulina platensis 794 to enhanced
      ultraviolet-B radiation resulted in an intensity-dependent inhibition of
      nitrogenase activity. In cultured cells that were treated with 0.5 mM SNP and
      enhanced UV-B for 6 h, nitrogenase activity increased by 47.3% compared with UV-B
      treated control cells. SNP apparently counteracted the decrease in nitrogenase
      activity caused by UV-B stress. NAC (a free radical scavenger) significantly
      increased nitrogenase activity, but PTIO (a nitric oxide scavenger) decreased
      nitrogenase activity in UV-B treated S. platensis 794. Thus, the free radical
      scavenger NAC and NO may counteract the effects of enhanced UV-B radiation. The
      activity of UV-B-inhibited nitrogenase did not recover upon transfer of exposed
      cells to fluorescent light, suggesting that the inhibition may be due to specific
      inactivation of the enzyme. By experimentally manipulating the inhibitors of
      photosystem-II activity, it was demonstrated that nitrogenase activity in
      cyanobacterium S. platensis 794 is limited by the amount of reductant and ATP.
      This result further confirmed that nitrogenase activity requires a continued and
      abundant supply of suitable reductant and ATP for conversion of N(2) to NH(3).
      The effects of UV-B treatment on nitratase activity were also examined, and
      enhanced UV-B radiation increased nitratase activity. In addition, enhanced UV-B
      in combination with SNP and NAC resulted in significant increases in the activity
      of nitratase.

PMID- 21188589
TI  - Molecular characterization of Morchella species from the Western Himalayan region
      of India.
AB  - The molecular diversity of thirty-two different Morchella cultures/fruiting
      bodies, collected from the Western Himalayan region was studied in this
      investigation. Considerable taxonomic confusion exists regarding many species of
      Morchella. Although classical taxonomy is helpful in identification for many
      ascomycetes, morels exhibit considerable morphological diversity and there is
      disagreement in the identification of morel species. Phylogenetic analyses based
      on DNA sequences could help in sorting out morel taxonomy which is essential to
      better define the morel diversity. In this study, sequence analysis revealed that
      in the Western Himalayan region of India, both yellow (M. crassipes, M.
      spongiola) and black morels (M. elata, M. angusticeps, and M. gigas) were
      prominent along with two Verpa species. Phylogenetic analysis by maximum
      parsimony, maximum likelihood and Bayesian inference revealed two different
      clades and a clear distinction between yellow and black morels.

PMID- 21188590
TI  - Shiga toxin-producing Escherichia coli O100:H-: stx2e in drinking water
      contaminated by waste water in Finland.
AB  - In November 2007, 450 m(3) of treated wastewater leaked into the drinking water
      distribution system contaminating the drinking water of over 10,000 inhabitants
      of Nokia, Southern Finland. Nearly 1,000 people visited the health centre because
      of gastroenteritis during the following 5 weeks. A wide range of enteric
      pathogens was found in the patients. The authors used the 16-plex PCR to
      investigate whether the five major diarrheagenic Escherichia coli pathotypes
      (EPEC, ETEC, STEC, EIEC or EAEC) were present in the contaminated drinking water
      and in the patients' stool samples. The contaminated drinking water was positive
      for genes characteristic of various E. coli pathotypes: pic, invE, hlyA, ent,
      escV, eae, aggR, stx(2) , estIa and astA. These genes, except stx(2), hlyA and
      invE, were also detected in the stool samples of the patients linked to this
      outbreak. A sorbitol positive, streptomycin resistant STEC strain was isolated
      from the drinking water, and belonged to the serotype O100:H(-), produced Stx2
      toxin (titre 1:8 by reversed-passive latex agglutination method), and carried the
      genes stx(2e), estIa and irp2.

PMID- 21188591
TI  - Phylogenetic diversity of rhizobia associated with horsegram [Macrotyloma
      uniflorum (Lam.) Verdc.] grown in South India based on glnII, recA and 16S-23S
      intergenic sequence analyses.
AB  - Horsegram [Macrotyloma uniflorum (Lam.) Verdc.) is an important grain legume and
      fodder crop in India. Information on root nodule endosymbionts of this legume in
      India is limited. In the present study, 69 isolates from naturally occurring root
      nodules of horsegram collected from two agro-eco-climatic regions of South India
      was analyzed by generation rate, acid/alkali reaction on YMA medium, restriction
      fragment length polymorphism analysis of 16S-23S rDNA intergenic spacer region
      (IGS), and sequence analyses of IGS and housekeeping genes glnII and recA. Based
      on the rDNA IGS RFLP by means of three restriction enzymes rhizobia were grouped
      in five clusters (I-V). By sequence analysis of 16S-23S rDNA IGS identified
      genotypes of horsegram rhizobia were distributed into five divergent lineages of
      Bradyrhizobium genus which comprised (I) the IGS type IV rhizobia and valid
      species B. yuanmingense, (II) the strains of IGS type I and Bradyrhizobium sp.
      ORS 3257 isolated from Vigna sp., (III) the strains of the IGS type II and
      Bradyrhizobium sp. CIRADAc12 from Acacia sp., (IV) the IGS type V strains and
      Bradyrhizobium sp. genospecies IV, and (V) comprising genetically distinct IGS
      type III strains which probably represent an uncharacterized new genomic species.
      Nearly, 87% of indigenous horsegram isolates (IGS types I, II, III, and V) could
      not be related to any other species within the genus Bradyrhizobium. Phylogeny
      based on housekeeping glnII and recA genes confirmed those results found by the
      analysis of the IGS sequence. All the isolated rhizobia nodulated Macrotyloma sp.
      and Vigna spp., and only some of them formed nodules on Arachis hypogeae. The
      isolates within each IGS type varied in their ability to fix nitrogen. Selection
      for high symbiotic effective strains could reward horsegram production in poor
      soils of South India where this legume is largely cultivated.

PMID- 21188592
TI  - Identification of Pythium insidiosum by nested PCR in cutaneous lesions of
      Brazilian horses and rabbits.
AB  - Pythium insidiosum is a fungus-like organism present in subtropical and tropical
      areas, such as Brazil, known to infect humans and various animal species. P.
      insidiosum is the etiological agent of pythiosis, an emerging and granulomatous
      disease characterized mainly by cutaneous and subcutaneous lesions in horses, the
      principal species affected. Accurate diagnosis of pythiosis and identification of
      its causal agent by microbiological and serological tests can be often difficult
      and inconclusive principally for horses and humans. The aim of this study was to
      evaluate the application of the previously described P. insidiosum-specific
      nested polymerase chain reaction (PCR) assay to directly detect P. insidiosum DNA
      in clinical and experimental lesions. Universal fungal primers (ITS1 and ITS4)
      were used during the first-round of PCR to amplify ITS1, 5.8s, and ITS2. A second
      round of PCR was conducted with P. insidiosum-specific primers (PI1 and PI2) to
      amplify a variable region within this ITS1. In this study, a total of 21 equine
      clinical samples (kunkers) and 28 specimens from experimentally infected rabbits
      were analyzed by nested PCR. The first-round of PCR generated 800-base pair
      products, and the second-round produced 105-base pair amplicons for each P.
      insidiosum-specific sample; no amplicons were generated in negative control
      samples. Our results suggest that nested PCR is an important and efficient tool
      for diagnosis of both endemic (horse samples) and experimental (rabbit samples)
      pythiosis.

PMID- 21188593
TI  - Paediatric cardiac computed tomography: a review of imaging techniques and
      radiation dose consideration.
AB  - The significant challenges involved in imaging the heart in small children (<15
      kg) have been addressed by, and partially resolved with improvement in temporal
      and spatial resolution secondary to the advent of new multi-detector CT
      technology. This has enabled both retrospective and prospective ECG-gated imaging
      in children even at high heart rates (over 100 bpm) without the need for beta
      blockers. Recent studies have highlighted that the radiation burden associated
      with cardiac CT can be reduced using prospective ECG-gating. Our experience shows
      that the resultant dose reduction can be optimised to a level equivalent to that
      of a non-gated study. This article reviews the different aspects of ECG-gating
      and the preferred technique for cardiac imaging in the young child (<15 kg). We
      summarize our evidenced based recommendations for readers, referencing recent
      articles and using our in house data, protocols and dose measurements discussing
      the various methods available for dose calculations and their inherent bias.

PMID- 21188594
TI  - Ultrasound-guided antegrade femoral access: comparison between the common femoral
      artery and the superficial femoral artery.
AB  - PURPOSE: The aim of this study was to compare ultrasound-guided access of the
      superficial femoral artery and the common femoral artery. MATERIAL AND METHODS:
      100 patients were randomized to ultrasound-guided access either into the SFA or
      the CFA. The two groups were compared with respect to technical success, access
      time and complications. In addition, a subgroup analysis was performed to compare
      the complication rate using manual compression versus closure devices for
      haemostasis. RESULTS: In the SFA group 49/50 patients were successfully accessed
      in the assigned location, compared to 41/50 in the CFA group (p = 0.016). The
      median access time was significantly faster in the SFA group (3 min 25 s)
      compared to the CFA group (5 min 26 s) (p < 0.001). The most frequent
      complications in the SFA group were pseudoaneurysms (16.3%) whereas access site
      haematomas (14.6%) were the most common complication in the CFA group. However,
      when looking at subgroup with closure devices there was no difference between the
      SFA group compared to CFA group (p = 1.000). CONCLUSION: Accessing the SFA was
      more often successful and significantly faster than puncturing the CFA. The
      pseudoaneurysm rate was higher in the SFA group when using manual compression,
      but similar when using closure devices.

PMID- 21188595
TI  - Single oral dose of micellar beta-carotene containing phospholipids improves beta
      carotene metabolism and plasma lipids in vitamin A-deficient rats.
AB  - BACKGROUND: Vitamin A (VA) deficiency is still a major health problem in the
      developing world. It affects various cellular functions and causes hypolipidemic
      effects in the body. beta-Carotene (BC)-rich foods are promising sources of VA.
      Phospholipids are reported to improve BC bioefficacy in normal rats, but whether
      they show similar effects during VA deficiency is unknown. AIM: To compare the BC
      metabolism and plasma lipid responses in VA-sufficient (+VA) and VA-deficient (
      VA) rats after a single oral dose of micellar BC containing phospholipids.
      METHODS: Groups of rats were fed with a VA-free diet and when they attained the
      weight-plateau stage of deficiency, both +VA and -VA rats were divided into 2
      groups (phosphatidylcholine, PC and lysophosphatidylcholine, LPC). Each group was
      further divided into 4 subgroups (1, 2, 3, and 6 h; n = 5 rats/time point) and
      determined the BC metabolism and plasma lipid responses to a post-dose of
      micellar BC with phospholipids. RESULTS: Maximal plasma BC (pmol/mL) levels were
      observed at 2 h in PC (1330 +/- 124) and at 1 h in LPC (1576 +/- 144) groups of
      +VA rats, and at 3 h in the PC (1621 +/- 158) and LPC (2248 +/- 675) groups of 
      VA rats. Liver BC (pmol/g) was maximum at 1 h in the PC (218 +/- 32) and LPC (249
      +/- 24) groups of +VA rats, and at 2 h in PC (228 +/- 23) and at 3 h in LPC (277
      +/- 18) groups of -VA rats. Plasma and liver BC levels were significantly (P <
      0.05) higher in -VA rats than +VA rats. Plasma retinyl palmitate (pmol/mL) was
      maximum at 3 h in PC (97 +/- 18) and at 2 h in LPC (126 +/- 14) groups of +VA
      rats, and at 2 h in the PC (92 +/- 13) and LPC (134 +/- 27) groups of -VA rats.
      The higher (P < 0.05) BC monoxygenase activity in -VA rats compared to +VA rats
      supports the BC bioefficacy. Plasma retinol level was improved in the PC and LPC
      groups, but the effect of LPC was higher (P < 0.05) than PC. Micellar
      phospholipids mitigate the VA deficiency-induced hypolipidemic effects.
      CONCLUSIONS: Micellar phospholipids improved BC metabolism and reinstated the
      hypolipidemic effects, perhaps by modifying the fat-metabolizing enzymes and
      repairing the altered intestinal membrane structure.

PMID- 21188596
TI  - The effects of PG102, a water-soluble extract from Actinidia arguta, on serum
      total IgE levels: a double-blind, randomized, placebo-controlled exploratory
      clinical study.
AB  - BACKGROUND: Recent studies have reported that blocking IgE has a potentially
      beneficial role in the treatment of various allergic diseases. Previously, we
      found that PG102, a water-soluble extract prepared from the edible fruits of
      Actinidia arguta, can effectively reduce IgE levels using murine models. AIMS: To
      evaluate the efficacy of PG102 at lowering levels of total IgE in asymptomatic
      subjects with atopy. METHODS: A total of 90 asymptomatic subjects with atopy were
      randomized equally to a PG102 group or a placebo control group and treated for 8
      weeks in a double-blind manner. Total serum IgE, eosinophilic cation protein
      (ECP), eotaxin, thymus, and activation-regulated chemokine (TARC), IL-4, IL-5,
      and IL-13 levels were measured. Eosinophil counts were determined before and
      after treatment, and results were compared. In addition, possible adverse
      reactions were thoroughly checked in this first human trial. RESULTS: Levels of
      total IgE significantly increased in the control group but showed no change in
      the PG102 group, and change differences between the control and PG102 groups were
      significant (+12.9%, vs.-5.7%, p = 0.015). Levels of ECP and eotaxin and
      eosinophil counts produced similar results. However, the other variables showed
      no significant changes after treatment. CONCLUSION: In this exploratory clinical
      trial, it was found that 8 weeks of treatment with PG102 effectively reduced the
      levels of total IgE in apparently asymptomatic subjects with atopy.

PMID- 21188597
TI  - Intranasal steroids or radiofrequency turbinoplasty in persistent allergic
      rhinitis: effects on quality of life and objective parameters.
AB  - Nasal congestion is a cardinal symptom of allergic rhinitis (AR). It is
      associated with decreased quality of life and difficult to treat as perceived by
      the patients. The purpose of this study is to evaluate the mid-term objective and
      subjective outcomes of management of nasal congestion using intranasal steroid
      (INS) therapy or radiofrequency turbinoplasty (RFT) in patients with persistent
      AR who have mucosal hypertrophy of the inferior turbinate. Fifty-five adult
      patients with AR, who claimed nasal congestion refractory to oral antihistamine
      (desloratadine) therapy, were randomized to INS (mometasone furoate) or
      temperature-controlled RFT treatment groups. Outcomes were determined by active
      anterior rhinomanometry, visual analog scale (VAS), and rhinoconjunctivitis
      quality of life questionnaire (RQLQ) at least 12 months after treatment. The
      median total nasal resistance decreased from 0.49 +/- 0.17 to 0.39 +/- 0.12
      Pa/cm(3)/s (p = 0.42), and from 0.51 +/- 0.18 to 0.29 +/- 0.07 Pa/cm(3)/s (p =
      0.003) with INS and RFT, respectively. RFT provided a better reduction in the
      perception of congestion in VAS scores. RQLQ scores improved significantly in
      both groups 1 year after treatment (mean follow-up 14.2 months) (p < 0.05). No
      adverse reactions were encountered in either group. Nasal congestion refractory
      to antihistamine appears to be improved by INS at some point, while reduced
      significantly by RFT in objective and subjective parameters. Both options are
      also effective in increasing the quality of life in patients with AR. RFT might
      be a safe and effective treatment of option in AR compared with INS.

PMID- 21188598
TI  - Continuous local analgesic therapy reduces pain after radical inguinal/iliacal
      lymph node dissection.
AB  - BACKGROUND: To optimize postoperative pain therapy after a radical
      inguinal/iliacal lymph node dissection (RILND), we investigated the influence of
      a continuous application of a local anaesthetic via a subfascial wound catheter
      in the abdominal wall in addition to a standardized systemic analgesia. MATERIALS
      AND METHODS: Between July 2007 and December 2009, 50 patients with stage III/IV
      of melanoma disease received, in an observational study, a systemic analgesic
      therapy. Of these patients, 30 were additionally treated with a subfascial
      catheter. Main outcome criterion was the pain under mobilisation at the first
      postoperative morning registered via a visual analogue score. Minor criteria were
      the analgesic requirement, the specific (surgical) complications and the day of
      discharge. RESULTS: Patients treated with the subfascial catheter had significant
      less pain at the first postoperative morning in rest (p = 0.02) and after
      mobilisation (p = 0.03) without increased morbidity (p = 0.45). Less patients of
      the treatment group needed a supplementary analgesic medication (p = 0.01) and
      were able to leave hospital earlier than patients of the control group (p =
      0.01). CONCLUSIONS: A subfascially placed pain catheter enhances postoperative
      pain therapy after RILND.

PMID- 21188599
TI  - Myxobolus supamattayai n. sp. (Myxosporea: Myxobolidae) from Thailand
      parasitizing the scale pellicle of wild mullet (Valamugil seheli).
AB  - A new myxosporean species, Myxobolus supamattayai n. sp., was isolated from wild
      mullet (Valamugil seheli) from the Andaman Sea, Thailand and described based on
      its morphology and molecular data. The myxosporean produced black plasmodia-like
      unique clinical sign on the skin with sporogonic stages and mature spores.
      Polysporous plasmodia, up to 2.5 mm in diameter, were found in epithelium tissue
      in the scale pocket. The spores measured 6.6 (6.2-7.0) MUm in length, 6.5 (6.2
      6.7) MUm in width, smooth, and round board to ellipsoidal in valvular view.
      Spores were enclosed with intracapsular process which represents 5-7 and 11-12 in
      amount revealed in light microscopy and ultrastructure, respectively. The polar
      capsules were pyriform and of equal size, measuring 3.5 (3.4-3.6) MUm in length
      and 2.0 (1.9-2.2) MUm in width, with four to five turns of polar filament
      arranged perpendicularly to longitudinal axis of the polar capsule. In
      conclusion, this new species is entirely different from those previously
      described; however, this finding was assured by the partial sequence of SSU rRNA
      gene (1,666 bp) analysis that differed from all known species of Myxobolus
      Butschli, 1882. The phylogenetic tree of the sequence data sets including those
      of freshwater and marine of Myxobolus spp. and the sister group (Henneguya spp.)
      was constructed to establish the relationship of this new species in Myxobolus
      clade and to explore its relations between their sister groups. Phylogenetic
      analysis indicated that a monophyletic group with Myxobolus spp. which infected
      mullet represents the newly formed species. These results suggested the
      presumably nearby evolution prospecting of Myxobolus species that were found in
      the same host.

PMID- 21188600
TI  - Seaweeds as a source of lead compounds for the development of new antiplasmodial
      drugs from South East coast of India.
AB  - The problems of resistant lines of Plasmodium falciparum are escalating. Twelve
      seaweeds species belong to five different families (Sargassaceae, Gracilariaceae,
      Hypneaceae, Corallinaceae and Halimedaceae) were collected from Mandapam coastal
      area, and the seaweeds extracts were tested for in vitro antiplasmodial activity
      against P. falciparum. Among the tested seaweeds, Gracilaria verrucosa (IC(50)
      5.55 MUg.ml(-1)) and Hypnea espera (IC(50) 8.94 MUg.ml(-1)) showed good
      antiplasmodial activity, and these results are comparable with positive controls
      such as artemether (IC(50) 4.09 MUg.ml(-1)) and chloroquine (IC(50) 19.59 MUg.ml(
      1)), respectively. Turbinaria conoides, Sargassum myriocystem, Hypnea valentiae
      and Jania rubens extracts showed IC(50) values between 5 to 50 MUg.ml(-1).
      Sargassum sp., Turbinaria decurrens and Halimeda gracilis extracts showed IC(50)
      values between 50 to 100 MUg.ml(-1). Gracilaria corticata, Jania adherens and
      Halimeda opuntia extracts showed IC(50) value of more than 100 MUg.ml(-1).
      Statistical analysis reveals that significant in vitro antiplasmodial activity (P
      < 0.05) was observed between the concentrations and time of exposure. The
      chemical injury to erythrocytes was also carried out, and it shows that no
      morphological changes in erythrocytes by the ethanolic extract of seaweeds
      extracts after 48 h of incubation. The in vitro antiplasmodial activity might be
      due to the presence of sugars, proteins, phenols and carboxylic acid in the
      ethanolic extracts of seaweeds. It is concluded from the present study that the
      ethanolic extracts of seaweeds of G. verrucosa and Hypnea espera possess lead
      compounds for development of antiplasmodial drugs.

PMID- 21188601
TI  - Opportunistic nature of the mammalian microsporidia: experimental transmission of
      Trachipleistophora extenrec (Fungi: Microsporidia) between mammalian and insect
      hosts.
AB  - Spores of Trachipleistophora extenrec, originally isolated from the muscles of
      the Madagascan insectivore Hemicentetes semispinosus and maintained by serial
      passage in severe combined immunodeficiency (SCID) mice, were fed to larvae of
      the Egyptian cotton leafworm Spodoptera littoralis. Extensive infection of larval
      tissues ensued and caused larval and pupal mortality. The development of T.
      extenrec in the insect host, studied both by light and electron microscopy,
      followed generally the same life cycle as in the mammalian host. However, some
      differences in the fine structure of the parasite grown in both types of hosts
      were found. Spores isolated from the insect host caused infection of SCID mice
      when injected intramuscularly. Our results suggest that T. extenrec may be
      originally an insect microsporidian. This likelihood is corroborated by its
      structural similarity and phylogenetic relationship to two other microsporidia
      having insects either as unique hosts (Vavraia culicis) or being able to infect
      both mammalian and insect host (Trachipleistophora hominis).

PMID- 21188602
TI  - Biochemical evidence of efficacy of potash alum for the control of dengue vector
      Aedes aegypti (Linnaeus).
AB  - Aedes aegypti is the primary vector of dengue, yellow fever and chikungunya in
      India and other South East Asian countries, and novel insecticides for vector
      control are urgently needed. In the present investigation, efficacy of potash
      alum, a traditionally known double salt in Indian and Chinese medicine system,
      was tested against the larvae of dengue vector, A. aegypti. LC(50,) LC(90) and
      LC(99) values were recorded for various instar larvae where I instar larvae were
      found to be the most susceptible and IV instar larvae as the least susceptible
      one. The LC(50) values of crude and standard potash alum of various instar larvae
      ranged between 15.29 and 48.53 ppm and 20.50-65.10 ppm, respectively. Biochemical
      changes were also evidenced in IV instar A. aegypti larvae following a sublethal
      exposure for 24 h in the levels of various nutrient reserves and primary
      metabolites such as sugar, glycogen, lipids and proteins suggesting possible mode
      of action responsible for larval mortality. Sugar and glycogen concentrations
      were measured as 24.6 and 10.67 MUg per five larvae in controls which were
      significantly (p<0.05) reduced by 32.11-93.98% and 39.26-94.47%, respectively, in
      larvae treated with crude alum. In controls, protein and lipid content were
      recorded as 210.74 and 94.71 MUg per five larvae which dropped up to 26.53% and
      25.5%, respectively, in larvae following treatment with crude alum. Moreover,
      drastic changes were also recorded for DNA content with 25.39-44.17% decrease in
      crude alum-treated larvae. It is evident from these results that potash alum, a
      fairly cheaper and readily available ecofriendly compound could be recommended as
      a potential chemical larvicide against dengue vector at mosquito breeding sites
      in the vicinity of human dwellings.

PMID- 21188603
TI  - Characterization and localization of saposin-like protein-2 (SAP-2) in Fasciola
      gigantica.
AB  - Fasciola gigantica saposin-like protein-2 (FgSAP-2) belongs to a family of lipid
      interacting proteins that are involved in the cytolysis of target cells. In this
      study, we have cloned and expressed FgSAP-2 and produced the antibody against
      this recombinant protein. Rabbit antiserum against rFgSAP-2 reacted with a
      similar native protein in the whole body extracts of the 4-week-old juvenile and
      adult stage, as well as a protein in their excretion-secretion, but not in the
      tegument. In situ hybridization and immunofluorescence detection revealed the
      presence of SAP-2 mRNA transcripts and proteins in the cecal epithelial cells of
      4-week-old juvenile and adult parasites, but not in the metacercariae and newly
      excysted juveniles. Moreover, SAP-2 is present only in the cecal epithelial cells
      lining the distal part of the digestive tract, but not in the tegumental-type
      epithelium lining the proximal part of the digestive tract. The rFgSAP-2 reacted
      with antisera from rabbits infected with F. gigantica metacercariae collected at
      5 weeks, but not at 2 weeks after infection. Anti-rFgSAP-2 did not exhibit any
      cross-reactivity with the other parasites' antigens, including Opisthorchis
      viverrini, Eurytrema pancreaticum, Cotylophoron cotylophorum, Fischoederius
      cobboldi, Gigantocotyle explanatum, Paramphistomum cervi, Setaria labiato
      papillosa, and Haemonchus placei. This finding indicated that SAP-2 is a unique
      protein that is expressed only in late juvenile and adult F. gigantica, and it
      could be considered for immunodiagnostic and as a vaccine candidate for
      fasciolosis.

PMID- 21188604
TI  - Qualitative and quantitative immunohistochemical evaluation of iNOS expression in
      the spleen of dogs naturally infected with Leishmania chagasi.
AB  - Nitric oxide (NO), the product of the nitric oxide synthase enzymes has been
      detected in Leishmania-infected animals. Besides its role on the immunity to
      infection, the role of NO and the inducible nitric oxide synthase (iNOS) in the
      pathogenesis of canine visceral leishmaniasis (CVL) is not well understood. This
      study aimed at evaluating immunohistochemically the iNOS expression in the spleen
      of dogs naturally infected (ID) with Leishmania (L.) chagasi compared with non
      infected dogs (NID). The ID was grouped according to the clinical form and the
      parasite load. Symptomatic dogs (SD) presented higher parasite load in relation
      to oligosymptomatic (OD) and asymptomatic (AD). The qualitative expression of
      iNOS was observed only in ID. SD presented strong and prominent labeling of iNOS,
      followed by OD and AD. Quantitatively, the results showed that the median
      expression of iNOS was higher in SD and OD compared to NID. Also, dog spleens
      with high parasitism load showed marked iNOS expression. Taken together, the
      results suggest that the expression of iNOS in the spleen of infected dogs with
      CVL was associated with clinical worsening of the disease and with high
      parasitism.

PMID- 21188605
TI  - Pharyngeal swallowing sound profile assessed after partial and total
      laryngectomy.
AB  - Recently, we described three components of a normal pharyngeal swallowing sound.
      The aim of the present study was to identify variations of these components using
      synchronized acoustic-radiological data in partially laryngectomized (PL) and
      totally laryngectomized (TL) patients before and after surgery. In this
      prospective study, from January 2003 to December 2006 we enrolled 14 patients in
      a PL group and 9 patients in a TL group. A fluoroscopy camera and a microphone
      were connected to a computer to obtain acoustic-radiological data (25 images/s).
      The subjects were asked to perform six deglutitions of 10 ml of barium
      suspension. The average durations of the sound variables were measured before and
      after surgery. The duration of the preoperative pharyngeal sound was 602 ms in
      the PL group and 562 ms in the TL group. It was significantly decreased after the
      TL (296 ms) and was increased after the PL (740 ms). A typical profile of the
      swallowing sound for each group was obtained. This study allowed us to describe
      the main variations of the pharyngeal swallowing sound induced by PL and TL. This
      noninvasive tool could be useful to assess postoperative swallowing function.

PMID- 21188606
TI  - Occurrence of unique three-celled megagametophyte and single fertilization in an
      aquatic angiosperm-Dalzellia zeylanica (Podostemaceae-Tristichoideae).
AB  - Angiosperms are characterized by the occurrence of double fertilization. However,
      Podostemaceae is considered an exception with the presence of only single
      fertilization (syngamy) though two male gametes are formed conventionally. To
      determine the cause for the failure of double fertilization in Dalzellia
      zeylanica (Gardn.) Wight, we closely tracked the movement of the male gametes
      from the time of pollen tube initiation to the time of entry into the
      megagametophyte to affect fertilization. We report for the first time, the
      presence of a novel type of three-nucleate/three-celled mature megagametophyte
      consisting of two synergids and an egg cell in D. zeylanica. Therefore, of the
      two male gametes formed in this plant, one fuses with the egg cell resulting in
      syngamy, whereas the other male gamete eventually degenerates due to the absence
      of its partner i.e. single polar nucleus of the central cell that degenerates
      prior to the entry of the pollen tube into the synergid. The present work not
      only highlights the highly reduced nature of megagametophyte but also the
      occurrence of single fertilization resulting in sperm selection in D. zeylanica.

PMID- 21188607
TI  - Comment on the article "Comparison of the effects of decompressive craniectomy on
      different neurosurgical diseases", by Kim K.T. et al.

PMID- 21188608
TI  - Influence of age and morphological characteristics on whole body, lumbar spine,
      femoral neck and 1/3 radius bone mineral apparent density in a group of Lebanese
      adolescent boys.
AB  - The purpose of this study was to analyse the relationships between age,
      morphological characteristics (weight, height, body mass index (BMI), fat and
      lean mass), daily calcium intake (DCI), physical activity and bone mineral
      apparent density (BMAD) of the whole body (WB), lumbar spine (L2-L4), femoral
      neck (FN) and 1/3 radius in a group of Lebanese adolescent boys. This study
      included 60 Lebanese adolescent (16.8 +/- 2.1 years old) boys. Body composition
      and bone mineral density (BMD) were assessed by dual-energy X-ray absorptiometry
      (DXA). BMAD values of the WB, L2-L4, FN and 1/3 radius were calculated. Physical
      activity and DCI were assessed using questionnaires. Age was positively related
      to WB, L2-L4 and 1/3 radius BMD and BMAD. Weight, lean mass and BMI were
      positively related to WB, L2-L4, FN and 1/3 radius BMD. Moreover, weight, lean
      mass and BMI were positively associated with L2-L4 and FN BMAD but not with BMAD
      of the WB and the 1/3 radius, while fat mass percentage was negatively associated
      with WB BMAD. In conclusion, this study shows that weight, lean mass and BMI are
      positively associated with BMAD of the weight-bearing bones (L2-L4 and FN) but
      not with BMAD of the WB and the 1/3 radius in adolescent boys.

PMID- 21188609
TI  - Simulated evolution of the vertebral body based on basic multicellular unit
      activities.
AB  - A numerical model based on the theory of bone remodeling is proposed to predict
      the evolution of trabecular bone architecture within the vertebral body and to
      investigate the process of degeneration in vertebral bone. In this study,
      particular attention is paid on the description of microstructure changes during
      the aging process. To take into account the effect of basic multicellular units
      (BMUs), a set of computational algorithms has been developed. It is assumed that
      BMU activation probability depends on the state of damaged bone tissue (damage
      accumulation, omega), which is evaluated according to previous research
      concerning bone fatigue damage. Combining these algorithms with the finite
      element method (FEM), the microstructure of vertebral bone has been predicted for
      up to 8 simulated years. Moreover, biomechanical material properties have been
      monitored to investigate the changes of vertebral bone with age. This study shows
      that the simulation based on BMU activities has the potential to define and
      predict the morphological evolution of the vertebral body. It can be concluded
      that the novel algorithms incorporating the coupled effects of both adaptive
      remodeling and microdamage remodeling could be utilized to gain greater insight
      into the mechanism of bone loss in the elderly population.

PMID- 21188610
TI  - Association between Helicobacter pylori infection and fibromyalgia syndrome.

PMID- 21188611
TI  - Computational modeling of growth: systemic and pulmonary hypertension in the
      heart.
AB  - We introduce a novel constitutive model for growing soft biological tissue and
      study its performance in two characteristic cases of mechanically induced wall
      thickening of the heart. We adopt the concept of an incompatible growth
      configuration introducing the multiplicative decomposition of the deformation
      gradient into an elastic and a growth part. The key feature of the model is the
      definition of the evolution equation for the growth tensor which we motivate by
      pressure-overload-induced sarcomerogenesis. In response to the deposition of
      sarcomere units on the molecular level, the individual heart muscle cells
      increase in diameter, and the wall of the heart becomes progressively thicker. We
      present the underlying constitutive equations and their algorithmic
      implementation within an implicit nonlinear finite element framework. To
      demonstrate the features of the proposed approach, we study two classical growth
      phenomena in the heart: left and right ventricular wall thickening in response to
      systemic and pulmonary hypertension.

PMID- 21188612
TI  - Production of heterologous polygalacturonase I from Aspergillus kawachii in
      Saccharomyces cerevisiae in batch and fed-batch cultures.
AB  - The pg1 gene from the filamentous fungus Aspergillus kawachii, which codifies for
      an acid polygalacturonase, was cloned into the pYES2 expression vector, giving
      rise to the pYES2:pg1DeltaI construct. Engineered Saccharomyces cerevisiae,
      transformed with pYES2:pg1DeltaI construct, both expressed and exported an active
      polygalacturonase with a MW of ~60 kDa and an isoelectric point of 3.7, similar
      to those reported for the wild-type enzyme. The recombinant enzyme has the
      ability to hydrolyze polygalacturonic acid at pH 2.5. Heterologous PG1 production
      was studied under controlled conditions in batch and fed-batch systems. A
      simultaneous addition of glucose and galactose was found to be the most suitable
      feeding strategy assayed, resulting in a final PG1 production of 50 U/ml. The
      production process proposed in this study could be applied for the industrial
      production of a novel and useful polygalacturonase.

PMID- 21188613
TI  - Elimination of glycerol and replacement with alternative products in ethanol
      fermentation by Saccharomyces cerevisiae.
AB  - Glycerol is a major by-product of ethanol fermentation by Saccharomyces
      cerevisiae and typically 2-3% of the sugar fermented is converted to glycerol.
      Replacing the NAD(+)-regenerating glycerol pathway in S. cerevisiae with
      alternative NADH reoxidation pathways may be useful to produce metabolites of
      biotechnological relevance. Under fermentative conditions yeast reoxidizes excess
      NADH through glycerol production which involves NADH-dependent glycerol-3
      phosphate dehydrogenases (Gpd1p and Gpd2p). Deletion of these two genes limits
      fermentative activity under anaerobic conditions due to accumulation of NADH. We
      investigated the possibility of converting this excess NADH to NAD(+) by
      transforming a double mutant (gpd1?gpd2?) with alternative oxidoreductase genes
      that might restore the redox balance and produce either sorbitol or propane-1,2
      diol. All of the modifications improved fermentative ability and/or growth of the
      double mutant strain in a self-generated anaerobic high sugar medium. However,
      these strain properties were not restored to the level of the parental wild-type
      strain. The results indicate an apparent partial NAD(+) regeneration ability and
      formation of significant amounts of the commodity chemicals like sorbitol or
      propane-1,2-diol. The ethanol yields were maintained between 46 and 48% of the
      sugar mixture. Other factors apart from the maintenance of the redox balance
      appeared to influence the growth and production of the alternative products by
      the genetically manipulated strains.

PMID- 21188614
TI  - Adaptive evolution of nontransgenic Escherichia coli KC01 for improved ethanol
      tolerance and homoethanol fermentation from xylose.
AB  - Due to its excellent capability to ferment five-carbon sugars, Escherichia coli
      has been considered one of the platform organisms to be engineered for production
      of cellulosic ethanol. Nevertheless, genetically engineered ethanologenic E. coli
      lacks the essential trait of alcohol tolerance. Development of ethanol tolerance
      is required for cost-effective ethanol fermentation. In this study, we improved
      alcohol tolerance of a nontransgenic E. coli KC01 (ldhA pflB ackA frdBC
      pdhR::pflBp6-aceEF-lpd) through adaptive evolution. During ~350 generations of
      adaptive evolution, a gradually increased concentration of ethanol was used as a
      selection pressure to enrich ethanol-tolerant mutants. The evolved mutant, E.
      coli SZ470, was able to grow anaerobically at 40 g l(-1) ethanol, a twofold
      improvement over parent KC01. When compared with KC01 for small-scale (500 ml)
      xylose (50 g l(-1)) fermentation, SZ470 achieved 67% higher cell mass, 48% faster
      volumetric ethanol productivity, and 50% shorter time to complete fermentation
      with ethanol titer of 23.5 g l(-1) and yield of 94%. These results demonstrate
      that an industry-oriented nontransgenic E. coli strain could be developed through
      incremental improvements of desired traits by a combination of molecular biology
      and traditional microbiology techniques.

PMID- 21188615
TI  - An upflow microaerobic sludge blanket reactor operating at high organic loading
      and low dissolved oxygen levels.
AB  - The activated sludge process (ASP) has high operational costs due to the need for
      aeration at dissolved O(2) (DO) levels of >=2 mg l(-1) and high capital costs to
      construct large reactors due to a low organic loading [typically 1 kg chemical
      oxygen demand (COD) m(-3) day(-1)]. A novel method for improving the energy use
      and treatment efficiency of the ASP via limited oxygenation (0.4 mg DO l(-1)) and
      high organic loading (6.2 kg COD m(-3) day(-1)) is proposed based on a laboratory
      scale ASP for ammonia-rich industrial wastewaters. The sludge blanket phenomenon
      and granulation occurred simultaneously in the upflow microaerobic reactor.

PMID- 21188616
TI  - alpha-(1 -> 3)-D-glucans from fruiting bodies of selected macromycetes fungi and
      the biological activity of their carboxymethylated products.
AB  - PURPOSE OF WORK: To show biological activity of carboxymethylated alpha-(1 -> 3)
      D-glucans isolated from the selected macromycetes fungi on human tumor and normal
      cells. Water-insoluble, alkali-soluble polysaccharides (WIP) were isolated from
      fruiting bodies of four macromycetes fungi: Lentinus edodes, Pleurotus ostreatus,
      Piptoporus betulinus and Laetiporus sulphureus. The structure of the
      polysaccharides was determined using composition analysis, methylation analysis,
      fourier transform infrared spectroscopy, and nuclear magnetic resonance
      spectroscopy. The chemical and spectroscopic investigations indicated that the
      polysaccharides were an alpha-(1 -> 3)-D-glucans. A biological activity analysis
      of the carboxymethylated (CM) alpha-(1 -> 3)-D-glucans was based on an assessment
      of their cytotoxic, mitochondrial metabolism-modulating, and free radical
      scavenging effects. The cytotoxic activity of the CM-glucans was concentration-
      and cell-type-dependent. The tested CM-glucans, generally, did not have a free
      radical scavenging effect. The CM-alpha-(1 -> 3)-D-glucans isolated from the
      selected macromycetes fungi are biologically active and may therefore be used as
      diet or therapy supplements.

PMID- 21188617
TI  - Regioselective deglycosylation of onion quercetin glucosides by Saccharomyces
      cerevisiae.
AB  - Bioconversion of quercetin glucosides using four generally recognized as safe
      (GRAS) organisms (Aspergillus oryzae, Bacillus subtilis, Lactobacillus plantarum,
      and Saccharomyces cerevisiae) was evaluated by measuring changes in the levels of
      quercetin compounds of onion. Of the four organisms, S. cerevisiae increased the
      content of quercetin-3-O-beta-D-glucoside (III; isoquercitrin) and quercetin
      (IV), whereas decreasing quercetin-3,4'-O-beta-D-glucoside (I) and quercetin-4'-O
      beta-D-glucoside (II). Also, S. cerevisiae converted authentic compound I to III,
      and II to IV, respectively. These results suggest that S. cerevisiae can be used
      to increase the levels of isoquercitrin (III), the most bioavailable quercetin
      compound in onion.

PMID- 21188618
TI  - Hydrolysis of cellulose in synergistic mixtures of beta-glucosidase and
      endo/exocellulase Cel9A from Thermobifida fusca.
AB  - The synergism between the endo/exocellulase, Cel9A, and beta-glucosidase (betagl)
      of Thermobifida fusca was investigated. Wild type betagl or S319C, a betagl
      mutant with significantly improved cellobiase activity, were added to Cel9A. Both
      wild type and mutant betagl enhanced the Cel9A hydrolysis of carboxymethyl
      cellulose (CMC) and filter paper by 50-100% compared to Cel9A alone. No
      enhancement occurred with addition of E388A, an inactive form of betagl. HPLC
      analysis showed that, with Cel9A alone, the resulting hydrolysate of glucose and
      cellobiose contained about half glucose; after addition of equimolar amounts of
      either wild type betagl or mutant S319C to Cel9A, the hydrolysate contained more
      than 85% glucose. betagl thus acted synergistically with Cel9A by converting
      cello-oligomers to glucose; this reduced the soluble sugar accumulation during
      hydrolysis of cellulose.

PMID- 21188619
TI  - Examining the drought stress transcriptome in cotton leaf and root tissue.
AB  - Growth, yield, and yield quality of cotton are greatly affected by water-deficit
      stress. We have identified the genes and associated metabolic pathways involved
      in the water-deficit stress response in leaf and root. Gene expression profiles
      were developed for leaf and root tissues subjected to slow-onset water deficit
      under controlled, glasshouse conditions. The water-deficit stress was
      characterized by leaf water potential of -23.1 bars for stressed tissue compared
      to -8.7 bars for fully-irrigated control plants and a corresponding decrease in
      net carbon assimilation to approximately 60% of the rates seen in the irrigated
      controls (30.3 +/- 4.7 MUmol CO(2) m(-2) s(-1) compared to 17.8 +/- 5.9 MUmol
      CO(2) m(-2) s(-1)). Profiling experiments revealed 2,106 stress-responsive
      transcripts, 879 classified as stress-induced, 1,163 stress-repressed, and 64
      showed reciprocal expression patterns in root and leaf. The majority of stress
      responsive transcripts had tissue-specific expression patterns and only 173 genes
      showed similar patterns of stress responsive expression in both tissues. A
      variety of putative metabolic and regulatory pathways were identified using
      MapMan software and the potential targets for candidate gene selection and
      ectopic expression to alter these pathways and responses are discussed.

PMID- 21188620
TI  - Phenotypic and gene expression analyses of a ploidy series of maize inbred Oh43.
AB  - Polyploidization has repeatedly occurred during plant evolution. Although
      autopolyploidy is the best model to characterize the polyploidization effects in
      a highly controlled manner, there are limited studies on autopolyploids compared
      to allopolyploids. To improve our understanding of autopolyploidy effects in
      maize, we developed an inbred Oh43 ploidy series consisting of the diploid (2X),
      tetraploid (4X) and hexaploid (6X) lines and compared their phenotypes and gene
      expression in the mature adult leaf tissue. Our phenotypic study showed that
      plants of higher ploidy exhibit increased cell size but slower growth rate, later
      flowering, fewer tassel branches, reduced stature and fertility. Two-dimensional
      difference gel electrophoresis (2D DIGE) and gel electrophoresis followed by
      liquid chromatography and mass spectrometry (GeLC-MS) assays of the leaf
      proteomes revealed ~40 and 26% quantitative differentially expressed (DE)
      proteins, respectively, at the per genome level. A small number of qualitative DE
      proteins were also identified in the GeLC-MS assay. The majority of the
      quantitative DE proteins found in the 2D DIGE assay were present in either the 4X
      versus 6X or the 2X versus 6X comparison but not the 2X versus 4X comparison.
      Aneuploidy in some 6X plants might contribute to the more extensive changes of
      gene expression per genome in the 6X. Most changes of the protein expression per
      genome are less than twofold. Less than 5% of the DE genes exhibit a positive or
      negative continuous correlation through the ploidy series between their protein
      expression per genome, and the genome copy number. Hence, in the Oh43 ploidy
      series, expression for most proteins in a cell increases linearly with ploidy.

PMID- 21188621
TI  - Role of cardiac isoform of alpha-2 macroglobulin in diabetic myocardium.
AB  - Earlier studies from one of the investigator's laboratory have demonstrated the
      presence of a high molecular weight protein (182 kDa) in the blood serum of
      laboratory animals subjected to pressure-induced cardiac hypertrophy and
      suggested that this protein may be involved in the development of cardiac
      hypertrophy. Studies have shown that this protein is also involved in earlier
      stages of cardiac complications associated with diabetes, but the role of this
      protein in diabetic heart is less understood. So we aimed to check whether this
      protein is having any protective role in diabetic heart. The protein was purified
      from serum of rats induced with cardiac hypertrophy and the purified protein was
      injected through tail vein of diabetic rats for further studies. The results of
      various antioxidant enzymes and the TBARS levels have indicated the antioxidant
      activity of this protein. Real-time PCR analysis of gene expression revealed the
      upregulation of certain muscle-specific genes like beta-MHC, MLC-2, and skeletal
      alpha actin in diabetic group and also in presence of 182-kDa protein. The
      results further showed a down regulation of genes such as cardiac alpha-actin and
      alpha- MHC implicating the role of this protein in the development of cardiac
      hypertrophy in diabetes. Increased cardiac hypertrophy as revealed by the
      expression of various genes and improved antioxidant potential in presence of 182
      kDa protein in diabetes at the earlier stages is beneficial for counteracting the
      myocardial damage associated with diabetes.

PMID- 21188622
TI  - Gomisin N enhances TNF-alpha-induced apoptosis via inhibition of the NF-kappaB
      and EGFR survival pathways.
AB  - Tumor necrosis factor (TNF-alpha) is a pleiotropic cytokine that plays an
      important role in the control of cell proliferation, differentiation, and
      apoptosis. TNF-alpha-induced apoptosis is limited by TAK1-mediated activation of
      NF-kappaB (mainly p65-p50 hetrodimer) signaling pathway. We have recently
      reported that TAK1 regulates phosphorylation of EGFR at Ser-1046/7 through p38
      MAPK, which cooperates with NF-kappaB in TNF-alpha-induced apoptosis. The present
      study investigated the effect of gomisins A and N, dibenzocyclooctadiene lignans
      isolated from the fruit of Schisandra chinensis, on TNF-alpha-induced apoptosis
      in HeLa cells. Gomisins A and N strongly promoted TNF-alpha-induced cleavage of
      caspase-3 and PARP-1, which are key markers of apoptosis. We found that gomisin
      N, but not gomisin A, inhibited the TNF-alpha-induced activation of NF-kappaB by
      suppressing the activation of IKKalpha. Gomisin N also inhibited p38-mediated
      phosphorylation of the EGFR at Ser-1046/7 and subsequent endocytosis of EGFR,
      another prosurvival pathway. The findings suggested that gomisin N enhanced TNF
      alpha-induced apoptosis by suppressing of NF-kappaB and EGFR signaling pathways.

PMID- 21188623
TI  - Matrix metalloproteinases and membrane damage markers in sera of patients with
      acute myocardial infarction.
AB  - Coronary artery disease is a multifunctional disease and represents one of the
      leading causes of death worldwide. Oxidative stress appears as an etiological
      factor for myocardial damage during acute myocardial infarction. Some data
      suggest that acute coronary syndromes may also be influenced by matrix
      metalloproteinases through degradation of the fibrous cap of vulnerable
      atherosclerotic lesions. It has been indicated that gelatinases A and B play a
      key role in acute myocardial infarction and deoxyribonuclease I has been
      postulated to be a novel early phase marker of disease. The aim was to study
      activity of gelatinases A and B in acute myocardial infarction and its
      association with some membrane damage markers. Seventy-five patients with disease
      and seventy-five healthy controls were enrolled. Activities of lactate
      dehydrogenase, malate dehydrogenase, and deoxyribonuclease I were estimated using
      standard spectrophotometric assay and isoforms of lactate and malate
      dehydrogenases were determined using direct zymography. Activity of
      dehydrogenases was significantly higher in patients, while deoxyribonuclease I
      was lower. Isoform 2 of lactate dehydrogenase was significantly higher in the
      patient group. Gelatinases A and B were detected only in patients group. The
      results suggest determination of serum malate dehydrogenase activity to be used
      as an additional parameter for acute myocardial infarction diagnosis. Those
      findings suggest important role of gelatinases A and B as biomarkers of early
      stage of acute myocardial infarction together with membrane damage parameters.

PMID- 21188624
TI  - Molecular cloning, expression, and functional analysis of a predicted
      sulfotransferase STF9 from Mycobacterium avium.
AB  - Sulfotransferases catalyze the transfer of sulfate group from para-nitrophenyl
      sulfate (pNPS) or 3'-phosphoadenosine-5'-phosphosulfate (PAPS) onto acceptor
      molecules in the biosynthesis of sulfate esters. Human pathogenic mycobacteria
      are known to produce numerous sulfated molecules on their cell surface which have
      been implicated as important mediators in host-pathogen interactions. The open
      reading frame stf9, a predicted homologue of sulfotransferase in the
      Mycobacterium avium genomic data, was cloned and over expressed in Escherichia
      coli. The recombinant STF9 conserved the characteristic PAPS binding motif of
      sulfotransferase and was purified as a 44 kDa soluble protein which exhibited
      transfer of sulfate group from pNPS (K (m) 1.34 mM, V (max) 7.56 nmol/min/mg)
      onto 3'-phosphoadenosine-5'-phosphate (K (m) 0.24 mM, V (max) 10.36 nmol/min/mg).
      The recombinant STF9 protein was also capable of transferring sulfate group from
      PAPS onto certain acceptor substrates in E. coli, and showed binding affinity to
      the PAP-agarose resin, supporting the sulfotransferase activity of the
      recombinant STF9 protein. This is the first report of molecular evidence for
      sulfotransferase activity of a protein from M. avium. Mutation of Arg96 to Ala
      and Glu170 to Ala abolishes sulfotransferase activity, indicating the importance
      of Arg96 and Glu170 in STF9 activity catalysis.

PMID- 21188626
TI  - Molecular study of porcine transmissible gastroenteritis virus after serial
      animal passages revealed point mutations in S protein.
AB  - Porcine respiratory coronavirus is related genetically to porcine transmissible
      gastroenteritis virus with a large deletion in S protein. The respiratory virus
      is a mutated form that may be a consequence of the gastroenteritis virus's
      evolution. Intensive passages of the virus in its natural host may enhance the
      appearance of mutations and therefore may contribute to any attenuated form of
      the virus. The objective of this study was to characterize the porcine
      transmissible gastroenteritis virus TMK22 strain after passages in piglets from
      1992 until 2007. A typical experimental infection, molecular characterization,
      and serological analysis were also carried out to further characterize and to
      evaluate any significant difference between strains. The sequence analysis showed
      two amino acid deletions and loss of an N-glycosylation site in transmissible
      gastroenteritis virus S protein after passages in piglets. Although these
      deletions were positioned at the beginning of the antigenic site B of S protein,
      no clinical differences were observed in piglets infected experimentally either
      with the native virus or the mutated one. Serological tests did not show any
      antibody reactivity difference between the two strains. In this article, we
      report that the S protein deletion did not affect the virus's pathogenicity. The
      variety of the virus's evolutionary forms may be a result, not only of the
      multiple passages in natural hosts, but also of other factors, such as different
      pathogens co-infection, nutrition, immunity, and others. Further studies need to
      be carried out to characterize the mutated strain.

PMID- 21188627
TI  - Treatment response in CP/ADHD children with callous/unemotional traits.
AB  - The current study examines the role of callous/unemotional (CU) traits in
      response to treatment among children with conduct problems (CP) and attention
      deficit/hyperactivity disorder (ADHD). Fifty-four children with CP/ADHD and 16
      controls (age = 9.48, SD = 1.58) took part in a summer treatment and research
      program. Simple correlations showed that CU and CP were associated with a number
      of treatment outcome measures. When examined together in regression analyses, CU
      and CP were uniquely associated with three treatment outcomes each (CU
      improvement in social skills and problem solving, negative behaviors in time-out;
      CP-time-outs per day, peer ratings, peer dislike). The implications for these
      findings with regard to treatment response in children with CP/ADHD with and
      without CU traits are explored.

PMID- 21188628
TI  - Conceptualizing the prospective relationship between social support, stress, and
      depressive symptoms among adolescents.
AB  - The goal of the current study is to examine the relationship amongst social
      support, stress, and depressive symptoms within a transactional and diathesis
      stress framework using a multi-wave, longitudinal design. At the initial
      assessment, adolescents (n = 258) completed self-report measures assessing social
      support (peer, classmate, parent, and total), dependent interpersonal stress,
      anxious symptoms, and depressive symptoms. Additionally, participants reported
      stress and symptomology in each of the four waves spanning six months. Results of
      time-lagged, idiographic, multilevel modeling indicated that stress mediated the
      relationship between lower parental, classmate, and total social support and
      subsequent depressive, but not anxious, symptoms. In contrast, lower levels of
      peer support were not associated with higher levels of stress and subsequent
      depressive symptoms. Additionally, only classmate support deficits significantly
      moderated the relationship between stress and depressive symptoms. Overall, the
      results suggest that deficits in parental and classmate support may play a
      greater role in contributing to adolescent depression as compared to deficits in
      peer support.

PMID- 21188629
TI  - The association between two polymorphisms in the TYMS gene and breast cancer
      risk: a meta-analysis.
AB  - Thymidylate synthase (TYMS), which catalyzes the conversion of deoxyuridine
      monophosphate to deoxythymidine monophosphate, is a central enzyme in the folate
      metabolic pathway. Epidemiological studies have evaluated the association between
      TYMS gene polymorphisms and breast cancer susceptibility; however, the published
      data are still inconclusive. To derive a more precise assessment of this
      relationship, we performed a meta-analysis based on currently available data by
      searching PubMed, EMBASE databases, and the Cochrane Library. A total of 10
      eligible studies were identified for the TYMS TSER polymorphism (six studies with
      2,718 cases and 3,423 controls) and for the TYMS TS3'-UTR polymorphism (five
      studies with 1,969 cases and 2,290 controls). The overall odds ratio (OR) and the
      corresponding 95% confidence interval (CI) showed a statistical association
      between the TSER polymorphism and breast cancer risk under homozygote comparison
      (2R/2R vs. non-2R/non-2R; OR 1.25; 95% CI 1.04-1.50), allele contrast (2R vs. non
      2R; OR 1.09; 95% CI 1.01-1.19) and the recessive model (OR 1.19; 95% CI 1.01
      1.39). In the subgroup analysis by ethnicity, a statistically significant
      increase in cancer risk was found among Caucasians for homozygote comparison (OR
      1.31; 95% CI 1.10-1.57), the allele contrast model (OR 1.12; 95% CI 1.02-1.23)
      and the dominant model (OR 1.40; 95% CI 1.00-1.95). For the TS3'-UTR
      polymorphism, significant effects were shown using the allele contrast model (OR
      1.33; 95% CI 1.03-1.73). However, the TS3'-UTR polymorphism increased breast
      cancer risk among Asian women (del6 vs. ins6; OR 1.41; 95% CI 1.01-1.98) but not
      Caucasian women using the homozygote comparison. In conclusion, our meta-analysis
      suggests that the TSER polymorphism may increase susceptibility to breast cancer
      in the Caucasian population and the TS3'-UTR polymorphism may be a genetic
      determinant for developing breast cancer in the Asian population; therefore,
      ethnic background should be carefully considered in further studies.

PMID- 21188631
TI  - Lymph node ratio, number of excised nodes and sentinel-node concepts in breast
      cancer.

PMID- 21188632
TI  - Results of a phase II study of pemetrexed as first-line chemotherapy in patients
      with advanced or metastatic breast cancer.
AB  - Palliation is the primary goal in metastatic breast cancer (MBC), and safe,
      efficacious, new single-agent options are needed. Pemetrexed, an antifolate,
      inhibits several folate-dependent enzymes involved in purine biosynthesis. The
      primary goal of this study was to determine the objective response rate in
      patients with advanced or MBC given pemetrexed as a first-line, dose-dense, every
      2-week chemotherapy. Women with HER2-negative advanced or MBC, without prior
      cytotoxic treatment for this stage of disease, were treated with intravenous
      pemetrexed 600 mg/m2 on Day 1 of each 14-day cycle. Standard dexamethasone, folic
      acid, and vitamin B(12) premedications were given. 37 patients enrolled; 36
      received >= 1 dose of pemetrexed and 35 were evaluable for response. Median age
      of patients was 61.4 years, 76% were hormone receptor positive (ER+ and/or PR+).
      Prior treatment included adjuvant chemotherapy (57%) and/or endocrine (65%).
      Patients received a median of 6 cycles of pemetrexed (range, 1-21). Based on 35
      evaluable patients, the overall response rate (ORR) was 26% (1 CR and 8 PR), and
      the clinical benefit rate (CR+ PR+ stable disease [SD] >= 6 months) was 40%.
      Median progression-free survival (PFS) was 4.1 months (range, <1-22.4). Median
      overall survival (OS) was 18.9 months (range, <1-27.7). Grades 3-4 treatment
      related toxicities included: neutropenia (36%), leukopenia (17%), fatigue (14%),
      and anemia (14%). Grade 1/2 alopecia was seen in 8% of patients. This phase II
      study of dose-dense, single-agent pemetrexed showed moderate activity in the
      first-line setting with acceptable toxicity and no significant alopecia.

PMID- 21188630
TI  - Resveratrol suppresses growth of cancer stem-like cells by inhibiting fatty acid
      synthase.
AB  - Resveratrol is a natural polyphenolic compound and has been shown to exhibit
      cardio-protective as well as anti-neoplastic effects on various types of cancers.
      However, the exact mechanism of its anti-tumor effect is not clearly defined.
      Resveratrol has been shown to have strong hypolipidemic effect on normal
      adipocytes and as hyper-lipogenesis is a hallmark of cancer cell physiology, the
      effect of resveratrol on lipid synthesis in cancer stem-like cells (CD24(
      )/CD44(+)/ESA(+)) that were isolated from both ER+ and ER- breast cancer cell
      lines was examined. The authors found that resveratrol significantly reduced the
      cell viability and mammosphere formation followed by inducing apoptosis in cancer
      stem-like cells. This inhibitory effect of resveratrol is accompanied by a
      significant reduction in lipid synthesis which is caused by the down-regulation
      of the fatty acid synthase (FAS) gene followed by up-regulation of pro-apoptotic
      genes, DAPK2 and BNIP3. The activation of apoptotic pathway in the cancer stem
      like cells was suppressed by TOFA and by Fumonisin B1, suggesting that
      resveratrol-induced apoptosis is indeed through the modulation of FAS-mediated
      cell survival signaling. Importantly, resveratrol was able to significantly
      suppress the growth of cancer stem-like cells in an animal model of xenograft
      without showing apparental toxicity. Taken together, the results of this study
      indicate that resveratrol is capable of inducing apoptosis in the cancer stem
      like cells through suppression of lipogenesis by modulating FAS expression, which
      highlights a novel mechanism of anti-tumor effect of resveratrol.

PMID- 21188633
TI  - Isolation, sequence analysis, and characterization of androgen receptor in
      Southern catfish, Silurus meridionalis.
AB  - Androgen receptor (AR), the mediator of androgen, plays important roles in the
      androgen signal pathway. In the present study, we isolated and analyzed the cDNA
      sequence and tissue distribution of androgen receptor in Southern catfish (scAR).
      The full-length cDNA of scAR contains 3,116 bp with an open reading frame (ORF)
      of 2,415 bp, encoding a protein of 804 amino acids (aa). Tissue distribution
      analysis of scAR revealed that it was expressed in all tissues examined, with no
      sexual dimorphism in the ovary and testis. Phylogenetic analysis and multiple
      amino acids sequence alignment indicated the close relationship and high
      similarity of scAR with ARs from cypriniform species. In addition, partial
      sequences of ARs from 7 other siluriform species were also isolated. Comparison
      of catfish ARs with those from other vertebrates revealed that an extra C
      terminal tail of about 20aa exists in all the ARs from siluriform fishes
      investigated, but not in other ARs. The extra sequence was resulted from a 4-bp
      insertion before the stop codon of other vertebrate ARs, and it was identical in
      ARs from siluriform species of the same genus but different among ARs from
      species of different genera. We report here for the first time that the ARs from
      siluriform species are longer in C-terminal than those from other vertebrates and
      it might be useful in reconstruction of the phylogenetic relationship among
      siluriform fishes. The significance of the extra C-terminal tail for AR function
      remains elusive.

PMID- 21188634
TI  - Identification and expression analysis of two growth hormone receptors in
      zanzibar tilapia (Oreochromis hornorum).
AB  - Growth hormone plays important roles in various physiological processes such as
      growth, metabolism, and reproduction. In this study, two cDNAs encoding growth
      hormone receptor (GHR) were isolated from the liver of zanzibar tilapia
      (Oreochromis hornornum). The two cDNAs were 2,831 and 2,044 bp in length and
      named GHR1 and GHR2, respectively. GHR1 and GHR2 shared 57.4% similarity in
      nucleotide sequences and 33.5% similarity in deduced amino acid sequences.
      Consequently, it was presumed that they were two different genes. Conserved
      regions of GHR1 and GHR2 in zanzibar tilapia were different from those of other
      vertebrates. For example, conserved box2 regions of GHR1 and GHR2 in zanzibar
      tilapia were, respectively, WVELM and WVEFT, while it was WVEFI for GHRs in other
      vertebrates. Similar to other fish species, GHR1 and GHR2 were expressed in
      brain, gill, liver, muscle, spleen, gonad, stomach, kidney, and pituitary in
      zanzibar tilapia. The expression levels were the highest in liver. Unlike fathead
      minnow (Pimephales promelas) and mossambique tilapia (O. mossambicus), the
      expression levels of GHR1 in most female fish tissues were higher than those in
      male fish. No significant difference in GHR2 expression was found in all the
      tissues in male and female of zanzibar tilapia. Under fasting condition, the
      expressions of GHRs and IGF-II were significantly up-regulated (P < 0.05) in
      liver, while the expression of IGF-I remained stable. This observation would
      contribute to understanding the evolution of the GHR family in further
      investigation of growth regulation of zanzibar tilapia.

PMID- 21188635
TI  - Characterization of the single-chain Fv-Fc antibody MBP10 produced in Arabidopsis
      alg3 mutant seeds.
AB  - ER resident glycoproteins, including ectopically expressed recombinant
      glycoproteins, carry so-called high-mannose type N-glycans, which can be at
      different stages of processing. The presence of heterogeneous high-mannose type
      glycans on ER-retained therapeutic proteins is undesirable for specific
      therapeutic applications. Previously, we described an Arabidopsis alg3-2
      glycosylation mutant in which aberrant Man(5)GlcNAc(2) mannose type N-glycans are
      transferred to proteins. Here we show that the alg3-2 mutation reduces the N
      glycan heterogeneity on ER resident glycoproteins in seeds. We compared the
      properties of a scFv-Fc, with a KDEL ER retention tag (MBP10) that was expressed
      in seeds of wild type and alg3-2 plants. N-glycans on these antibodies from
      mutant seeds were predominantly of the intermediate Man(5)GlcNAc(2) compared to
      Man(8)GlcNAc(2) and Man(7)GlcNAc(2) isoforms on MBP10 from wild-type seeds. The
      presence of aberrant N-glycans on MBP10 did not seem to affect MBP10 dimerisation
      nor binding of MBP10 to its antigen. In alg3-2 the fraction of underglycosylated
      MBP10 protein forms was higher than in wild type. Interestingly, the expression
      of MBP10 resulted also in underglycosylation of other, endogenous glycoproteins.

PMID- 21188637
TI  - Alexithymia, verbal ability and emotion recognition.
AB  - Although previous studies seem to indicate that alexithymic individuals have a
      deficit in their ability to recognize emotional stimuli, none had studied the
      relationship between alexithymia and verbal and non verbal abilities and their
      possible role in emotion recognition. The aim of the present study is to further
      investigate the relationship between alexithymia and emotion recognition ability.
      In particular we studied whether this relationship is mediated by verbal ability.
      Thirty-five students were selected from a group of 91 University students
      previously screened for alexithymia (Toronto Alexithymia Scale; TAS-20).
      Participants were shown black and white slides depicting facial expression of the
      following emotions: anger, sadness, disgust, surprise, happiness and fear.
      Compared to low alexithymic participants, and, more importantly, taking verbal IQ
      into account, high alexithymic and low alexithymic participants did not differ in
      emotion recognition.

PMID- 21188636
TI  - Promoter of the AlSAP gene from the halophyte grass Aeluropus littoralis directs
      developmental-regulated, stress-inducible, and organ-specific gene expression in
      transgenic tobacco.
AB  - In our recent published work it has been demonstrated that AlSAP, a gene encoding
      an A20/AN1 zinc-finger protein (stress-associated protein) of the C4 halophyte
      grass Aeluropus littoralis, is inducible by various abiotic stresses and by
      hormonal stimuli. To further investigate the regulation of the gene, a 586-bp
      genomic fragment upstream of the AlSAP translated sequence has been isolated,
      cloned, and designated as the "Pr ( AlSAP )" promoter. Sequence analysis of "Pr (
      AlSAP )" revealed the presence of cis-regulatory elements which could be required
      for abiotic stress, abscisic acid (ABA), and salicylic acid (SA) responsiveness
      and for tissue-specific and vascular expression. The Pr ( AlSAP ) promoter was
      fused to the beta-glucuronidase (gusA) gene and the resulting construct
      transferred into tobacco. Histochemical assays of stably transformed tobacco
      plants showed that Pr ( AlSAP ) is active in this heterologous C3 system. While
      full-length gusA transcripts accumulated in whole 15, 30, and 45-day-old plants,
      GUS histochemical staining was only observed in leaves and stems of 45-day-old,
      or older, transgenic seedlings. Histological sections prepared at this stage
      revealed activity localized in leaf veins (phloem and bundle sheath) and stems
      (phloem and cortex) but not in roots. Furthermore, gusA transcripts accumulated
      in an age-dependent manner with a basipetal pattern in leaf and stem tissues
      throughout the plant. In flowers, GUS expression was detected in sepals only. The
      accumulation of gusA transcripts was up-regulated by salt, dehydration, ABA, and
      SA treatment. Altogether, these results show that, when used in a heterologous
      dicot system, Pr ( AlSAP ) is an age-dependent, abiotic-stress-inducible, organ
      specific and tissue-specific promoter.

PMID- 21188638
TI  - Velocity field measurements of valvular blood flow in a human superficial vein
      using high-frequency ultrasound speckle image velocimetry.
AB  - This study aims to investigate the blood flow around the perivalvular area in a
      human superficial vein using high-frequency ultrasound (HFUS) speckle image
      velocimetry. HFUS B-mode images were captured from the superficial veins of human
      lower extremity with a 35-MHz transducer. To measure the instantaneous velocity
      fields of blood flow, a cross-correlation particle image velocimetry (PIV)
      algorithm was applied to two B-mode images that were captured consecutively. The
      echo speckles of red blood cells (RBCs) were used as flow tracers. In the
      vicinity of the venous valve, the opening and closing motions of valve cusps were
      simultaneously visualized with the phasic variation of velocity fields. Large
      scale vortices were observed behind the sinus pockets while the main bloodstream
      was directed proximally. This measurement technique combining PIV algorithm and
      HFUS B-mode imaging was found to be unique and useful for investigating the
      hemodynamic characteristics of blood flow in the perivalvular area and for
      diagnosing venous insufficiency and valve abnormality in superficial blood
      vessels.

PMID- 21188639
TI  - 99 mTc-MIBI washout as a complementary factor in the evaluation of idiopathic
      dilated cardiomyopathy (IDCM) using myocardial perfusion imaging.
AB  - Rapid technetium-99 m methoxyisobutylisonitrile (99 mTc-MIBI) washout has been
      shown to occur in impaired myocardia. This study is based on the hypothesis that
      scintigraphy can be applied to calculate the myocardial 99 mTc-MIBI washout rate
      (WR) to diagnose and evaluate heart failure severity and other left ventricular
      functional parameters specifically in idiopathic dilated cardiomyopathy (IDCM)
      patients. Patients with IDCMP (n = 17; 52.65 +/- 11.47 years) and normal subjects
      (n = 6; 49.67 +/- 10.15 years) were intravenously administered 99 mTc-hexakis-2
      methoxyisobutylisonitrile (99 mTc-MIBI). Next, early and delayed planar data were
      acquired (at 3.5-h intervals), and electrocardiogram (ECG)-gated myocardial
      perfusion single photon emission computed tomography (SPECT) was performed. The
      99 mTc-MIBI WR was calculated using early and delayed planar images. Left
      ventricular functional parameters were also analyzed using quantitative gated
      SPECT (QGS) data. In target group, myocardial WRs (29.13 +/- 6.68%) were
      significantly higher than those of control subjects (14.17 +/- 3.31%; P < 0.001).
      The 99 mTc-MIBI WR increased with the increasing severity of the NYHA functional
      class (23.16 +/- 1.72% for class I, 30.25 +/- 0.95% for class II, 32.60 +/- 6.73%
      for class III, and 37.50 +/- 7.77% for class IV; P = 0.02). The WR was positively
      correlated with the end-diastolic volume (EDV) index (r (2) = 0.216; beta =
      0.464; P = 0.02 [ml/m(2)], the end-systolic volume (ESV) index (r (2) = 0.234;
      beta = 0.484; P = 0.01 [ml/m(2)]), the summed motion score (SMS) (r (2) = 0.544;
      beta = 0.738; P = 0.00), and the summed thickening score (STS) (r (2) = 0.656;
      beta = 0.810; P = 0.00); it was negatively correlated with the left ventricular
      ejection fraction (LVEF) (r (2) = 0.679; beta = -0.824; P = 0.00). It can be
      concluded that 99 mTc-MIBI scintigraphy might be a valuable molecular imaging
      tool for the diagnosis and evaluation of myocardial damage or dysfunction
      severity.

PMID- 21188640
TI  - Acromegaly as a cause of 1,25-dihydroxyvitamin D-dependent hypercalcemia: case
      reports and review of the literature.
AB  - Growth hormone excess has been associated with hypercalciuria and
      nephrolithiasis. Hypercalcemia in acromegaly is rare and usually due to
      coexistent primary hyperparathyroidism. To report two cases of 1,25
      dihydroxyvitamin D (1,25 (OH)(2) D)-dependent hypercalcemia in cromegaly. A 50
      year-old female with 2 years history of hypercalcemia presented with features of
      acromegaly. Serum calcium (Ca) was 10.9 mg/dl (8.6-10.2), parathyroid hormone
      (PTH) 20 pg/ml (10-65), PTH-related peptide undetectable, and 1,25 (OH)(2) D 119
      pg/ml (15-75). Insulin-like growth factor 1 (IGF1) was 911 ng/ml (49-292) and
      growth hormone (GH) 14.5 ng/ml (0.03-10). MRI showed a 1.7 cm pituitary tumor.
      Transsphenoidal adenectomy (TSA) resulted in normalization of IGF1, GH, Ca, and
      1,25 (OH)(2) D (50 pg/ml) and complete tumor resection. A 52-year-old female was
      diagnosed with visual field deficits on routine exam. MRI showed a 3 cm invasive
      pituitary macroadenoma. IGF1 was 416 ng/ml (87-238) and GH 75.8 (0-6.0) ng/ml.
      Incidentally, she was found with high Ca of 10.8 mg/dl (8.9-10.3) associated with
      PTH 19 pg/ml and 1,25 (OH)(2) D66 pg/ml. Postoperatively, IGF1 and GH remained
      abnormal (440 and 12.8 ng/ml, respectively), while MRI showed parasellar tumor
      residue. Ca remained high (10.1-11.1 mg/dl), along with elevated 1,25 (OH)(2) D
      level (81.3 pg/ml). In both cases, other causes of hypercalcemia were ruled out.
      We present 2 cases of 1,25 (OH)(2) D-dependent hypercalcemia associated with
      growth hormone excess. Complete resection of tumor produced biochemical remission
      of acromegaly and normalization of calcium and 1,25 (OH)(2) D levels, while
      incomplete resection was associated with persistent 1,25 (OH)(2) D-dependent
      hypercalcemia. Acromegaly should be considered a cause of 1,25 (OH)(2) D
      dependent hypercalcemia.

PMID- 21188642
TI  - Simultaneous quantification of marker components in Ojeok-san by HPLC-DAD.
AB  - A systematic high-performance liquid chromatography-diode array detection (HPLC
      DAD) method was developed for the rapid, accurate, and simultaneous
      quantification of eight marker compounds, paeoniflorin, 6-gingerol, decursin,
      glycyrrhizin, cinnamic acid, hesperidin, poncirin and magnolol, in Ojeok-san, a
      traditional Korean herbal medicine. These compounds were separated in less than
      50 min using a Dionex C(18) column with a gradient elution system of water and
      methanol at a flow rate of 1 ml/min. All calibration curve of standard components
      showed excellent linearity (R(2) > 0.9922). Limits of detection (LOD) and limits
      of quantification (LOQ) ranged from 0.01 to 0.11 MUg/ml and 0.03 to 0.34 MUg/ml,
      respectively. The relative standard deviations (RSDs) of data of the intra- and
      inter-day experiments were less than 2.15 and 2.60%, respectively. The accuracy
      of recovery test ranged from 94.27 to 107.68% with RSD values 0.15-3.61%. The
      results of validation showed that the HPLC method was stable and very accurate
      for the quantification of eight marker components in Ojeok-san.

PMID- 21188643
TI  - Five new phenylpropanoid glycosides from Paraboea glutinosa (Gesneriaceae).
AB  - Five new phenylpropanoid glycosides, paraboside A, paraboside B, paraboside I,
      paraboside II and paraboside III along with the three known phenylethanoids,
      nuomioside A, caleolarioside B, isonuomioside A have been isolated from the whole
      plants of Paraboea glutinosa. The structures of the new compounds have been
      elucidated on the basis of spectroscopic data.

PMID- 21188644
TI  - Application of 1H-NMR spectroscopy to validation of berberine alkaloid reagents
      and to chemical evaluation of Coptidis Rhizoma.
AB  - Berberine, palmatine, and coptisine are major pharmacologically active
      protoberberine alkaloids in Coptidis Rhizoma, and have been used as indices for
      chemical evaluation of the crude drug. (1)H-NMR spectroscopy was applied to
      determination of purities of commercial reagents of protoberberine alkaloids. The
      purities of the alkaloids were calculated from the ratios of the intensities of
      the H-13 singlet signal at about delta 8.7 ppm of target protoberberine alkaloids
      to integration of a hexamethyldisilane (HMD) signal at 0 ppm. The concentration
      of HMD was corrected with SI traceability using potassium hydrogen phthalate of
      certified reference material (CRM) grade. The purity of the reagent estimated by
      the (1)H-NMR was, in general, lower than that claimed by the manufacturer,
      leading to over-estimation of the alkaloid contents of Coptidis Rhizoma when
      determined by HPLC. The present quantitative (1)H-NMR method was also applicable
      to direct determination of protoberberine alkaloid contents in Coptidis Rhizoma.

PMID- 21188645
TI  - Ameliorative effects of Eriobotrya japonica seed extract on cellular aging in
      cultured rat fibroblasts.
AB  - To investigate the effects of Eriobotrya japonica seed extract (ESE) on cellular
      aging, intracellular calcium homeostasis in young and senescent cells was
      analyzed using a rat fibroblast culture as an in vitro model system and a calcium
      imaging technique. The application of bradykinin (BK) transiently elicited
      intracellular calcium ion (Ca(2+)) increased in most of the young fibroblasts,
      whereas these responses were scarcely observed or were significantly attenuated
      in senescent cells. However, the long-term treatment of senescent cells with ESE
      (for 7 days) dose-dependently increased the amplitude of BK-induced responses and
      the percentage of BK-responding cells. In particular, most senescent cells could
      respond to BK with long-term treatment with ESE (1.0% or 2.0%), an effect that
      reinstated the percentage of BK-responding cells to the same level as that in
      young cells. The effects of ESE on amplitude or percentage of responding cells
      were not observed in young cells. Moreover, the time to half decay, which was
      significantly longer in senescent cells than that in young cells, was shortened
      in senescent cells with long-term treatment with ESE. These results suggest that
      treatment with an adequate concentration of ESE renders BK-induced Ca(2+)
      dynamics in senescent cells similar to those in young cells. Therefore, ESE can
      retard and/or protect against cellular aging and may be useful for elucidating
      the antiaging processes.

PMID- 21188646
TI  - Overcoming a "probable" diagnosis in antimitochondrial antibody negative primary
      biliary cirrhosis: study of 100 sera and review of the literature.
AB  - Serum anti-mitochondrial antibodies (AMA) are the serological hallmark of primary
      biliary cirrhosis (PBC), yet up to 15% of PBC sera are AMA negative at routine
      indirect immunofluorescence (IIF) while being referred to as "probable" cases.
      The diagnostic role of PBC-specific antinuclear antibodies (ANA) remains to be
      determined. We will report herein data on the accuracy of new laboratory tools
      for AMA and PBC-specific ANA in a large series of PBC sera that were AMA-negative
      at IIF. We will also provide a discussion of the history and current status of
      AMA detection methods. We included IIF AMA-negative PBC sera (n=100) and sera
      from patients with other chronic liver diseases (n=104) that had been
      independently tested for IIF AMA and ANA; sera were blindly tested with an ELISA
      PBC screening test including two ANA (gp210, sp100) and a triple (pMIT3) AMA
      recombinant antigens. Among IIF AMA-negative sera, 43/100 (43%) manifested
      reactivity using the PBC screening test. The same test was positive for 6/104
      (5.8%) control sera. IIF AMA-negative/PBC screen-positive sera reacted against
      pMIT3 (11/43), gp210 (8/43), Sp100 (17/43), both pMIT3 and gp210 (1/43), or both
      pMIT3 and Sp100 (6/43). Concordance rates between the ANA pattern on HEp-2 cells
      and specific Sp100 and gp210 ELISA results in AMA-negative subjects were 92% for
      nuclear dots and Sp100 and 99% for nuclear rim and gp210. Our data confirm the
      hypothesis that a substantial part of IIF AMA-negative (formerly coined
      "probable") PBC cases manifest disease-specific autoantibodies when tested using
      newly available tools and thus overcome the previously suggested diagnostic
      classification. As suggested by the recent literature, we are convinced that the
      proportion of AMA-negative PBC cases will be significantly minimized by the use
      of new laboratory methods and recombinant antigens.

PMID- 21188647
TI  - Auto-antibodies as emergent prognostic markers and possible mediators of ischemic
      cardiovascular diseases.
AB  - During the last 15 years, a growing body of evidence supported the fact that auto
      antibodies represent not only emergent markers but also active mediators of
      cardiovascular disease (CVD), clinically represented mostly by acute coronary
      syndrome (ACS) and stroke. There is a contrasted relationship between auto
      antibodies and CVD, some being protective, while others acting as potential risk
      factors. Therefore, we performed a review of the literature on the respective
      cardiovascular prognostic value of the most relevant auto-antibodies in ACS and
      stroke, and their putative pathophysiological properties in atherogenesis. This
      review highlights auto-antibodies as active modulators of the innate immune
      system in atherogenesis (either toward a pro- or anti-inflammatory response), or
      by affecting basal heart rate regulation (anti-apoA-1 IgG). Given their apparent
      prognostic independency towards traditional cardiovascular risk factors, the data
      available in the literature indicates that some of those auto-antibodies could be
      of valuable help for cardiovascular risk stratification in the future, especially
      because their deleterious effects have been shown to be potentially abrogated in
      vivo and in vitro by existing therapeutic modalities. Although evidence in humans
      is currently lacking, these studies may open innovative therapeutic perspectives
      for CVD in the future.

PMID- 21188649
TI  - The clinical significance of anti-beta-1 adrenergic receptor autoantibodies in
      cardiac disease.
AB  - Autoimmune response against myocardial antigens is evident in numerous heart
      diseases. Both the induction of an autoimmune response and the pathogenesis of
      autoimmune heart diseases are not fully understood. The humoral immune response
      may play an important role via induction of cardiomyocyte apoptosis, alteration
      of myocardial mechanical and electrophysiological functions, and activation of
      the complement system and cell-mediated cytotoxicity. Anti-beta-1 adrenergic
      receptor antibodies appear to contribute to the pathogenesis of dilated
      cardiomyopathy, heart failure, and Chagas disease. Herein, we review the current
      knowledge relating to anti-beta-1 adrenergic receptor antibodies: their potential
      role in heart diseases and the potential benefits of a targeted therapy against
      their apparently destructive effects. Patients with dilated cardiomyopathy with
      circulating stimulatory anti-beta-1 adrenergic receptor autoantibodies are
      probably at a higher risk for adverse outcome and should be treated with
      adrenergic receptor antagonists, and possibly with immunotherapy. Further
      research is required to determine which patients will gain additional clinical
      benefits from anti-autoantibody-targeted therapy.

PMID- 21188648
TI  - Genetics and immunopathogenesis of IgA nephropathy.
AB  - IgA nephropathy (IgAN) is the most common glomerulonephritis in the world. The
      hallmark of IgAN is underglycosylation in the hinge region of IgA1. Increasing
      evidence supports the underglycosylated IgA-containing immune-complex including
      IgG antibodies against the glycans of the hinge region of IgA1 are key factors
      for mesangial deposition and then trigger inflammation and glomerular injury. The
      polymeric IgA is produced after aberrant mucosal IgA response. The displacement
      of mucosal B cells to systemic lymphoid organs and bone marrow may arise from
      abnormal trafficking of lymphocytes along the mucosa-bone marrow axis involving
      changes of chemokines and adhesion molecules. This review will summarize the
      works on the genetics, the mucosal and systemic IgA immune response, mechanism of
      underglycosylation of IgA1, and the pathological effect of mesangial IgA
      deposition in IgAN.

PMID- 21188650
TI  - Therapeutic perspectives in atopic dermatitis.
AB  - Therapy of atopic dermatitis should comprise emollients, topical
      glucocorticosteroids, or calcineurin inhibitors, phototherapies,
      immunosuppressants like cyclosporin A, and other treatments. All these treatments
      should be improved, thanks to research. But new therapeutic perspectives should
      be given by topical anti-inflammatory substances, selective glucocorticoid
      receptor agonists, probiotics, interferon gamma, TNFalpha inhibitors, inhibition
      of T cells or B cells, inhibition of IgE binding, and many other possibilities.

PMID- 21188651
TI  - An improved technique for chromosomal analysis of human ES and iPS cells.
AB  - Prolonged in vitro culture of human embryonic stem (hES) cells can result in
      chromosomal abnormalities believed to confer a selective advantage. This
      potential occurrence has crucial implications for the appropriate use of hES
      cells for research and therapeutic purposes. In view of this, time-point
      karyotypic evaluation to assess genetic stability is recommended as a necessary
      control test to be carried out during extensive 'passaging'. Standard techniques
      currently used for the cytogenetic assessment of ES cells include G-banding
      and/or Fluorescence in situ Hybridization (FISH)-based protocols for karyotype
      analysis, including M-FISH and SKY. Critical for both banding and FISH techniques
      are the number and quality of metaphase spreads available for analysis at the
      microscope. Protocols for chromosome preparation from hES and human induced
      pluripotent stem (hiPS) cells published so far appear to differ considerably from
      one laboratory to another. Here we present an optimized technique, in which both
      the number and the quality of chromosome metaphase spreads were substantially
      improved when compared to current standard techniques for chromosome
      preparations. We believe our protocol represents a significant advancement in
      this line of work, and has the required attributes of simplicity and consistency
      to be widely accepted as a reference method for high quality, fast chromosomal
      analysis of human ES and iPS cells.

PMID- 21188653
TI  - Influence of E-cadherin-mediated cell adhesion on mouse embryonic stem cells
      derivation from isolated blastomeres.
AB  - Efforts to efficiently derive embryonic stem cells (ESC) from isolated
      blastomeres have been done to minimize ethical concerns about human embryo
      destruction. Previous studies in our laboratory indicated a poor derivation
      efficiency of mouse ESC lines from isolated blastomeres at the 8-cell stage (1/8
      blastomeres) due, in part, to a low division rate of the single blastomeres in
      comparison to their counterparts with a higher number of blastomeres (2/8, 3/8
      and 4/8 blastomeres). Communication and adhesion between blastomeres from which
      the derivation process begins could be important aspects to efficiently derive
      ESC lines. In the present study, an approach consisting in the adhesion of a
      chimeric E-cadherin (E-cad-Fc) to the blastomere surface was devised to recreate
      the signaling produced by native E-cadherin between neighboring blastomeres
      inside the embryo. By this approach, the division rate of 1/8 blastomeres
      increased from 44.6% to 88.8% and a short exposure of 24 h to the E-cad-Fc
      produced an ESC derivation efficiency of 33.6%, significantly higher than the
      2.2% obtained from the control group without E-cad-Fc. By contrast, a longer
      exposure to the same chimeric protein resulted in higher proportions of
      trophoblastic vesicles. Thus, we establish an important role of E-cadherin
      mediated adherens junctions in promoting both the division of single 1/8
      blastomeres and the efficiency of the ESC derivation process.

PMID- 21188652
TI  - Potential of human embryonic stem cells in cartilage tissue engineering and
      regenerative medicine.
AB  - The current surgical intervention of using autologous chondrocyte implantation
      (ACI) for cartilage repair is associated with several problems such as donor site
      morbidity, de-differentiation upon expansion and fibrocartilage repair following
      transplantation. This has led to exploration of the use of stem cells as a model
      for chondrogenic differentiation as well as a potential source of chondrogenic
      cells for cartilage tissue engineering and repair. Embryonic stem cells (ESCs)
      are advantageous, due to their unlimited self-renewal and pluripotency, thus
      representing an immortal cell source that could potentially provide an unlimited
      supply of chondrogenic cells for both cell and tissue-based therapies and
      replacements. This review aims to present an overview of emerging trends of using
      ESCs in cartilage tissue engineering and regenerative medicine. In particular, we
      will be focusing on ESCs as a promising cell source for cartilage regeneration,
      the various strategies and approaches employed in chondrogenic differentiation
      and tissue engineering, the associated outcomes from animal studies, and the
      challenges that need to be overcome before clinical application is possible.

PMID- 21188654
TI  - Improved functional activity of bone marrow derived circulating progenitor cells
      after intra coronary freshly isolated bone marrow cells transplantation in
      patients with ischemic heart disease.
AB  - OBJECTIVES: There is growing evidence that intracoronary autologous bone marrow
      cells transplantation (BMCs-Tx) in patients with chronic myocardial infarction
      beneficially affects postinfarction remodelling. In this randomized controlled
      study we analyzed the influence of intracoronary autologous freshly isolated bone
      marrow cells transplantation by use of point of care system on cardiac function
      and on the functional activity of bone marrow derived circulating progenitor
      cells (BM-CPCs) in patients with ischemic heart disease (IHD). METHODS: 56
      patients with IHD were randomized to either received freshly isolated BMC-Tx or a
      control group that did not receive cell therapy. The functional activity of BM
      CPCs in peripheral blood (PB) was measured by migration assay and colony forming
      unit assay pre- and 3, 6 as well as 12 months after procedure. Global ejection
      fraction (EF) and infarct size area were determined by left ventriculography.
      RESULTS: Intracoronary transplantation of autologous freshly isolated BMCs led to
      a significant reduction of infarct size and an increase of global EF as well as
      infarct wall movement velocity after 3 and 12 months follow-up compared to
      control group. The colony-forming capacity of BM-CPCs significantly increased 3,
      6 and 12 months after cell therapy compared to pre BMCs-Tx and control group (CFU
      E: p < 0.001, CFU-GM: p < 0.001). Likewise, we found significant increase of
      migratory response to stromal cell-derived factor 1 (SDF-1) and vascular
      endothelial growth factor (VEGF) after cell therapy compared to pre BMCs-Tx (SDF
      1: p < 0.001, VEGF: p < 0.001) and to control (SDF-1: p < 0.001, VEGF: p <
      0.001). There was no significant difference of migratory- and colony forming
      capacity between pre- and 3, 6, 12 months after coronary angiography in control
      group without cell therapy. CONCLUSIONS: Intracoronary transplantation of
      autologous freshly isolated BMCs by use of point of care system may lead to
      improvement of BM-CPCs functional activity in peripheral blood, which might
      increase the regenerative potency in patients with IHD.

PMID- 21188655
TI  - Development of feeder-free culture systems for generation of ckit+sca1+
      progenitors from mouse iPS cells.
AB  - Patient-specific therapeutic cells derived from induced pluripotent stem (iPS)
      cells may bypass the ethical issues associated with embryonic stem (ES) cells and
      avoid potential immunological reactions associated with allogenic
      transplantation. It is critical, for the ultimate clinical applicability of iPS
      cell-derived therapies, to establish feeder-free cultures that ensure efficient
      differentiation of iPS cells into therapeutic progenitors. It is also necessary
      to understand if iPS cell-derived progenitors differ from those derived from ES
      cells. In this study, we compared the efficiency of three different feeder-free
      cultures for differentiating mouse iPS cells into ckit+sca1+ hematopoietic
      progenitor cells (HPCs) and compared how differentiation and functionality varies
      between ES and iPS cells. Our results indicated that both iPS and ES cells can be
      efficiently differentiated into HPCs in suspension cultures supplemented with
      secretion factors from mouse bone marrow stromal cells (OP9-DL1 conditioned
      medium). The functionality of these cells was demonstrated by differentiation
      into CD11c+ dendritic cells (DCs). Both ES and iPS-derived DCs expressed
      activation molecules (CD86, CD80) in response to LPS stimulation and stimulated T
      cell proliferation in a mixed lymphocyte reaction (MLR). Extensive quantitative
      RT-PCR studies were used to study the differences in gene expression profiles of
      ckit+sca1+ cells generated from the various culture systems as well as
      differences between ES-derived and iPS-derived cells. We conclude that a feeder
      free system using stromal conditioned medium can efficiently generate HPCs as
      well as functional DCs from iPS cells and the generated cells have similar gene
      expression profile as those from ES cells.

PMID- 21188656
TI  - Predicting sentinel lymph node metastasis in breast cancer with
      lymphoscintigraphy.
AB  - OBJECTIVE: Lymphoscintigraphy is an effective method for detecting sentinel lymph
      nodes (SLNs). However, the rate and degree of SLN detection is not uniform. We
      quantified SLNs detected with lymphoscintigraphy, and investigated correlations
      with factors that may influence detection. We then attempted to predict SLN
      metastasis from lymph node counts, comparing the predictions to subsequent biopsy
      results. METHODS: We assessed lymph node counts in 100 breast cancer patients in
      whom a single SLN was detected with a fixed lymphoscintigraphy procedure. We
      examined correlations between the counts and factors known to influence
      lymphoscintigraphic SLN detection (age, body mass index, tumor size, and presence
      or absence of metastasis), and determined reference values (lymph node counts of
      10.0, 19.4 and 53.0) which were used to predict SLN metastasis in 100 subsequent
      patients. The predictions were then compared with the SLN biopsy findings.
      RESULTS: SLN counts correlated strongly with the presence or absence of
      metastasis, with metastasis-positive lymph nodes showing significantly lower
      counts than negative nodes (p < 0.001). Prediction of SLN metastasis achieved a
      100% positive predictive value at a reference value of 10.0, and a 100% negative
      predictive value at a reference value of 53.0. At a reference value of 19.4, the
      sensitivity, specificity, and diagnostic accuracy were 77.8, 73.2, and 74.0%,
      respectively. CONCLUSIONS: The SLN counts detected with lymphoscintigraphy were
      significantly lower in metastasis-positive lymph nodes than in metastasis
      negative lymph nodes. This suggests that prediction of SLN metastasis in breast
      cancer is possible using lymphoscintigraphy.

PMID- 21188657
TI  - Relationship of detection rate of PET cancer screening examinees and risk
      factors: analysis of background of examinees.
AB  - OBJECTIVE: PET cancer screening is performed widely in Japan as opportunistic
      screening, but no study has focused on the correlation with various cancer risk
      factors and the seeking bias of examinees and cancer detection rate. Analyzing
      our large series of PET cancer screening data, correlations with cancer detection
      rates according to general cancer risk factors and PET detection survey were
      reviewed, and the selection bias of the medical examinees was determined.
      METHODS: 19189 examinees who underwent PET cancer screening were enrolled. Using
      logistic-regression analysis, we analyzed correlations between smoking
      history/drinking history/cancer family history and detection rates of thyroid
      cancer/breast cancer/colorectal cancer/lung cancer, which are the main
      malignancies detected in PET cancer screening. In addition, we evaluated seeking
      bias of examinees, analyzing correlations between the presence of cancer risk
      factors and prior screening checkups at other institutions to our PET cancer
      screening using a matched case-control study. RESULTS: Cancer detection rates by
      FDG-PET were 1.17% (224/19189), being much higher than those of standard cancer
      mass screenings. In males, statistically significant correlations were seen
      between lung cancer and smoking, and between prostate cancer and a family history
      of prostate cancer, but not between the detection rates of three other types of
      cancer (thyroid cancer/lung cancer/colorectal cancer) and other cancer risk
      factors. In females, detection rates of four types of cancer (thyroid cancer/lung
      cancer/colorectal cancer/breast cancer) were significantly higher in the
      examinees without cancer risks, and subgroup analysis according to types of
      cancer did not indicate significant correlations either. The matched case-control
      study evaluating seeking bias indicated that a significant proportion of the
      examinees with cancer risks had undergone prior cancer screening at other
      institutions. CONCLUSIONS: Our study indicated that there was significant seeking
      bias for prior screening of examinees, with this accounting for the fact that
      this study did not find a significant correlation between cancer risks and cancer
      detection rates. The results of our study indicated that PET cancer screening can
      provide high cancer detection rates.

PMID- 21188658
TI  - 18F-FDG-PET/CT findings in primary pulmonary mixed squamous cell and glandular
      papilloma.
AB  - A 55-year-old female had an abnormal shadow on chest radiograph. Computed
      tomography (CT) revealed a 26-mm tumor mass in the left upper lobe. No malignant
      findings were obtained by bronchoscopic cytology or histopathological
      diagnostics, but on positron emission tomography with 18F-fluorodeoxyglucose (FDG
      PET) examination the maximum SUV was 9.01 in accordance with the tumor mass
      shadow on CT. Video-assisted thoracoscopic surgery was performed as clinically
      suspected of lung cancer, and the diagnosis was pulmonary mixed squamous cell and
      glandular papilloma (PMSGP). Primary PMSGP is extremely rare, and this is the
      first to describe the PET findings of this disease.

PMID- 21188659
TI  - Impact of radioguided occult lesion localization on the correct excision of
      malignant breast lesions: effect of histology and tumor size.
AB  - AIM: To evaluate the impact of radioguided occult lesion localization (ROLL) in
      the correct location and excision of malignant breast lesions, and analyze if
      these results are affected by the histology and tumor size. MATERIALS AND
      METHODS: A total of 105 patients with occult breast lesions were studied. The
      mean age was 55 years. An intralesional dose of 18.5 MBq of 99mTc-labeled
      macroaggregated human albumin (AMA) was administered using stereotaxic
      mammography or ultrasound. Surgical resection was carried out with the help of a
      gammadetector probe. In the histological study, disease-free margin was defined
      by a distance between the tumor lesion and the surgical margin of more than 1 mm.
      The possible influence of tumor histology and lesion diameter with respect to
      free/affected margins was analyzed. RESULTS: Correct radiotracer placement was
      achieved in 100/105 of the cases (95.2%). In the remaining 5 cases (4.8%),
      radiotracer placement was incorrect, with 2 of them being malignant lesions that
      were found by macroscopic inspection, and the other 3 having benign pathology.
      Among the malignant lesions (44 cases), correct placement of the radiotracer was
      achieved in 42 cases (95.5%). Of these 42 malignant lesions, in which the ROLL
      was correctly performed, free surgical margins were obtained in 24 cases (57.1%),
      while the other 18 (42.9%) had infiltrated surgical margins. The most common
      histological type among the malignant lesions was invasive ductal carcinoma
      (71.4%). The histological types with an increased frequency of infiltration of
      surgical margins were invasive and microinvasive cancer (94.4%). All the affected
      margins were in lesions greater than 10 mm, and the highest incidence was in
      those between 20 and 30 mm (55.5%). CONCLUSION: In our experience, the advantages
      of the ROLL technique are a precise localization of malignant breast lesions
      (95.5%) and an increased probability of a complete excision with free margins in
      more than one half of them. Nevertheless, special consideration should be taken
      when dealing with invasive and microinvasive cancers and in those exceeding 10 mm
      because of their higher incidence of infiltrated margins.

PMID- 21188660
TI  - Semiquantitative analysis of C-11 methionine PET may distinguish brain tumor
      recurrence from radiation necrosis even in small lesions.
AB  - OBJECTIVE: (11)C-Methionine positron emission tomography (MET-PET) has been used
      to distinguish brain tumor recurrence from radiation necrosis. Because the
      spatial resolution of conventional PET scanners is low, partial volume effect
      (PVE) may decrease the detectability of small tumor recurrence. The aim of this
      study is to investigate the diagnostic value of MET-PET upon semiquantitative
      analyses in particular PVE-affected small lesions. METHODS: First, we performed a
      phantom experiment to investigate what size lesion is affected by PVE. This study
      included 29 patients (33 lesions) suspected of recurrent brain tumors by magnetic
      resonance imaging (MRI) after radiation therapy. All of them received MET-PET.
      Semiquantitative analysis was performed using maximum standardized uptake value
      (SUVmax) and lesion-versus-normal ratio (L/N ratio). ROC analysis was also
      assessed about the diagnostic value of MET-PET. RESULTS: From the result of the
      phantom experiment, lesions smaller than 20 mm in brain mode or smaller than 30
      mm in whole-body mode were defined as PVE-affected lesions. Histological analysis
      or clinical follow-up confirmed the diagnosis of tumor recurrence in 22 lesions,
      and radiation necrosis in 11 lesions. L/N ratios of recurrence and necrosis for
      overall lesions were 1.98 +/- 0.62 and 1.27 +/- 0.28, respectively (p < 0.01). In
      the PVE-affected lesions, L/N ratio for recurrence (1.72 +/- 0.44) was also
      significantly higher than that for necrosis (1.20 +/- 0.11) (p < 0.01). On the
      ROC analysis for the PVE-affected lesions, the area under the curve for L/N ratio
      (0.897) was significantly higher than that for SUVmax (0.718) (p < 0.05). These
      areas under the curve were almost equal to that of overall lesions for L/N ratio
      (0.886) and for SUVmax (0.738). CONCLUSIONS: Semiquantitative analysis of MET
      provided high diagnostic value even for PVE-affected small lesions. MET-PET
      enables early diagnosis of recurrence of brain tumor in the follow-up after the
      radiation therapy.

PMID- 21188661
TI  - Heat shock proteins in porcine ovary: synthesis, accumulation and regulation by
      stress and hormones.
AB  - The present studies aimed to understand the interrelationships between stress,
      hormones and heat shock proteins (HSPs) in the ovary. We examined (1) whether
      HSP70.2, HSP72 and HSP105/110 can be produced and accumulated in porcine ovarian
      tissue, (2) whether these HSPs could be indicators of stress, i.e. whether two
      kinds of stress (high temperatures and malnutrition/serum deprivation) can affect
      them, and (3) whether some hormonal regulators of ovarian functions (insulin-like
      growth factor (IGF)-I, leptin and follicle-stimulating hormone (FSH)) can affect
      these HSPs and response of ovaries to HSP-related stress. We analysed the
      expression of HSP70.2, HSP72 and HSP105/110 mRNA (by using real-time reverse
      transcriptase polymerase chain reaction) in porcine ovarian granulosa cells, as
      well as the accumulation of HSP70 protein (by using sodium dodecyl sulphate
      polyacrylamide gel electrophoresis-Western) in either whole ovarian follicles and
      granulose cells cultured at normal (37.5 degrees C) or high (41.5 degrees C)
      temperature, with and without serum and with and without IGF-I, leptin and FSH.
      Expression of mRNA for HSP70.2, HSP72 and HSP105/110 in ovarian granulosa cells
      and accumulation of HSP70 protein in whole ovarian follicles and granulosa cells
      were demonstrated. In all the groups, addition of either IGF-I, leptin and FSH
      reduced the expression of HSP70.2, HSP72 and HSP105/110 mRNA. Both high
      temperature, serum deprivation and their combination resulted in increase in
      mRNAs for all three analysed HSPs. Additions of either IGF-I, leptin and FSH
      prevented the stimulatory effect of both high temperature and serum deprivation
      on the transcription of HSP70.2, HSP72 and HSP105/110. In contrast, high
      temperature reduced accumulation of peptide HSP70 in both ovarian follicles and
      granulosa cell. Serum deprivation promoted accumulation of HSP70 in granulosa
      cells, but not in ovarian follicles. Addition of IGF-I, leptin and FSH was able
      to alter accumulation of HSP70 in both follicles and granulosa cells. The present
      observations suggest (1) that HSPs can be synthesised in ovarian follicular
      granulosa cells; (2) that hormones (IGF-I, leptin and FSH) can inhibit, whilst
      stressors (both high temperature and malnutrition/serum deprivation) can
      stimulate transcription of HSP70.2, HSP72 and HSP105/110 genes, whilst heat
      stress, but not malnutrition, can promote depletion of HSP70 in ovarian cells,
      and (3) that hormones (IGF-I, leptin and FSH) can prevent stress-related changes
      in HSPs. The application of HSPs as indicators and mediators of stress and
      hormones on ovarian functions, as well as use of hormones and HSPs as anti
      stressor molecules, are discussed.

PMID- 21188662
TI  - Thermotolerance and hsp70 heat shock response in the cold-stenothermal chironomid
      Pseudodiamesa branickii (NE Italy).
AB  - To better understand the physiological capability of cold-stenothermal organisms
      to survive high-temperature stress, we analyzed the thermotolerance limits and
      the expression level of hsp70 genes under temperature stress in the alpine midge
      Pseudodiamesa branickii (Diptera Chironomidae). A lethal temperature (LT(100)) of
      36 degrees C and a lethal temperature 50% (LT(50)) of 32.2 degrees C were found
      for the cold-stenothermal larvae after short-term shocks (1 h). Additional
      experiments revealed that the duration of the exposure negatively influenced
      survival, whereas a prior exposure to a less severe high temperature generated an
      increase in survival. To investigate the molecular basis of this high
      thermotolerance, the expression of the hsp70 gene family was surveyed via semi
      quantitative reverse transcription-polymerase chain reaction analysis in treated
      larvae. The constitutive (hsc70) and inducible (hsp70) forms were both analyzed.
      Larvae of P. branickii showed a significant up-regulation of inducible hsp70 gene
      with increasing temperatures and an over-expression of both hsp70 and hsc70 by
      increasing the time of exposure. Different from that was shown in many cold
      stenothermal Antarctic organisms, P. branickii was able to activate hsp70 genes
      transcription (equal to heat shock response) in response to thermal stress.
      Finally, the unclear relationship between hsp70 expression and survival led us to
      surmise that genes other than hsp70 and other processes apart from the
      biochemical processes might generate the high thermaltolerance of P. branickii
      larvae. These results and future high-throughput studies at both the
      transcriptome and proteome level will improve our ability to predict the future
      geographic distribution of this species within the context of global warming.

PMID- 21188664
TI  - Patients' perception of care during image-guided breast biopsy in a rural
      community breast center: communication matters.
AB  - This retrospective study surveyed women about their experience with image-guided
      breast biopsies in a rural cancer center. Our study objectives were to determine:
      women's perception of their emotional and physical comfort during the biopsy; the
      clarity and acceptability of the communication about the biopsy, as well as the
      methods used to provide the results of her biopsy and treatment options; and the
      overall impressions of the technical and personal care she received. A single
      mailed survey of 500 biopsy patients. The response rate was 43% (n = 215). Prior
      to their biopsy, 22% had been concerned that the biopsy would be painful and 43%
      were concerned that the biopsy might show cancer. Almost all women rated the
      communication about the biopsy procedure as understandable (99%) and accurately
      reflecting their experience (99%.). Most (77%) patients characterized the biopsy
      as producing minimal discomfort, although 5% disagreed. Most patients (98%)
      characterized their physician and technologists as caring about their emotional
      and physical comfort. Most patients felt that the typical 1-day wait to receive
      the results of their biopsy was reasonable (90%) and that the use of the phone to
      convey the results was acceptable (90%). On comparing patients with a diagnosis
      of cancer to those without, there was no difference in the level of satisfaction
      with the use of the phone to communicate biopsy results. This study offers
      encouragement that communication practices can alleviate the anxiety of women
      undergoing image-guided breast cancer biopsies.

PMID- 21188663
TI  - Effect of cigarette smoke and dexamethasone on Hsp72 system of alveolar
      epithelial cells.
AB  - Smoking is the leading risk factor of chronic obstructive pulmonary disease
      (COPD) and lung cancer. Corticosteroids are abundantly used in these patients;
      however, the interaction of smoking and steroid treatment is not fully
      understood. Heat shock proteins (Hsps) play a central role in the maintenance of
      cell integrity, apoptosis and cellular steroid action. To better understand
      cigarette smoke-steroid interaction, we examined the effect of cigarette smoke
      extract (CSE) and/or dexamethasone (DEX) on changes of intracellular heat shock
      protein-72 (Hsp72) in lung cells. Alveolar epithelial cells (A549) were exposed
      to increasing doses (0; 0.1; 1; and 10 MUM/MUl) of DEX in the medium in the
      absence(C) and presence of CSE. Apoptosis, necrosis, Hsp72 messenger-ribonucleic
      acid (mRNA) and protein expression of cells were measured, and the role of Hsp72
      on steroid effect examined. CSE reduced the number of viable cells by
      significantly increasing the number of apoptotic and necrotic cells. DEX dose
      dependently decreased the ratio of apoptosis when CSE was administered, without
      change in necrosis. CSE - DEX co-treatment dose-dependently increased Hsp72 mRNA
      and protein expression, with the highest level measured in CSE + DEX (10) cells,
      while significantly lower levels were noted in all respective C groups.
      Pretreatment with Hsp72 silencing RNA confirmed that increased survival observed
      following DEX administration in CSE-treated cells was mainly mediated via the
      Hsp72 system. CSE significantly decreases cell survival by inducing apoptosis and
      necrosis. DEX significantly increases Hsp72 mRNA and protein expression only in
      the presence of CSE resulting in increased cellular protection and survival. DEX
      exerts its cell protective effects by decreasing apoptotic cell death via the
      Hsp72 system in CSE-treated alveolar epithelial cells.

PMID- 21188670
TI  - A study of the relationship between impulsiveness and obsessiveness in the
      general population. Inconsistency of the idea of the spectrum.
AB  - INTRODUCTION: The obsessivity and the impulsivity as personality traits have been
      object of few studies on the general population. The authors outline as objective
      to study if such features are co-existing constructs, as advocate some authors or
      the opposite extremes of a continuum as assert other. MATERIAL AND METHODS: They
      are studied the answers to a questionnaire on obsessive traits of the personality
      (MIRAP) and other referred to the impulsivity as trait, also, (ECIRYC) of a
      random sample of 418 subject extracted of the general population. They are
      applied multivariate statistic analysis technical (Factorial Analysis,
      Correspondence Analysis, and linear Regression Analysis) to establish the type of
      relationship that have the two studied personality traits. RESULTS: The total
      scores of the MIRAP and the ECIRYC are correlated of a manner statistically
      significant (r = .39; p< .01). The Correspondence Analysis of those total scores
      distributed in deciles and two linear Regression Analysis show, also, a direct
      relationship between both traits that it is statistically significant. The
      obsessivity and the impulsivity do not correlate with the principal factor of the
      opposite trait. All the factors of both traits are grouped mutually in a factor
      in a positive way, except the impulsive factor "haste" that makes it negatively
      with the obsessive factor "order". CONCLUSIONS: Our results indicate that the
      obsessivity and the impulsivity, as personality traits, they are constructs
      convergent and not opposite poles of a continuum. But, simultaneously, one of the
      five factors of each trait ("haste" and "order"), yes are behaved as opposite
      extremes of a continuum, within conceptual framework, wider, of the traits to
      those which belong.

PMID- 21188671
TI  - Comparison of the effectiveness of venlafaxine in peri- and postmenopausal
      patients with major depressive disorder.
AB  - INTRODUCTION: This study examines the difference in the efficacy and tolerability
      of an antidepressant inhibiting the reuptake of norepinephrine and serotonin-
      IRNS--on climacteric patients diagnosed of major depressive disorder, comparing
      the therapeutic response between perimenopausal and postmenopausal patients.
      METHODS: Observational, prospective, open-label, multicenter study 24 weeks
      study. The sample consisted of women between 45 and 55 years diagnosed of major
      depressive disorder. The study drug was venlafaxine extended release at doses
      according to the investigator's clinical criteria. The efficacy was assessed
      using repeated measures of the scales: Hamilton Depression Rating Scale and Blatt
      Kupperman Menopausal Index. RESULTS: 36 depressed women were included in the
      study and 35 completed it. The patient's age range was 47 to 55 years old.
      Throughout the study, a significant clinical improvement in depressive and
      hormonal symptoms was seen. The comparison of the pattern of improvement,
      according to the menstrual status of the patients, showed no significant
      different between pre and postmenopausal patients. Perimenopausal women reported
      a higher rate of adverse events. CONCLUSION: The Venlafaxine was effective in
      treating depressive and hormonal symptoms regardless of the menstrual status of
      climacteric patients with a slightly worse tolerance in perimenopause.

PMID- 21188672
TI  - Adaptation and validation of the semi-structured interview for Psychological
      Autopsy (SSIPA) in Spanish.
AB  - INTRODUCTION:  OBJECTIVES: The aim of this work was to adapt and validate into
      Spanish the Semi-Structured Interview for Psychological Autopsy (SSIPA). METHOD:
      The SSIPA consists of 69 items distributed into four modules: precipitants and/or
      stressors, motivation, lethality, and intentionality. The original instrument was
      translated from Portuguese into Spanish and backtranslated by bilinguals persons.
      The resulting questionnaire was compared with the original and discussed by an
      expert panel. The adapted instrument was then applied to the relatives of 26
      presumed suicide cases in Ourense (Spain) who voluntarily accepted to
      participate. Interviews were digitally recorded and evaluated using a decision
      making algorithm by the interviewer and two independent judges blind to the
      results of the others. RESULTS: Interrater agreement was measured using Kappa
      statistics. Participation in the study (27.6%) was similar to that obtained in
      the original study in Brazil >(20%). The Kappa values obtained were statistically
      significant. Correlation index was considered good (k>0.60) or very good (k>
      0.80) in 15 steps including 3 out of 4 final steps of each module and the final
      result of the autopsy; moderate (k> 0.40) in 8 steps, 3 of them located in the
      motivation's module; and weak (k> 0.20) just in 2 steps. CONCLUSIONS: The Spanish
      version of the SSIPA is a reliable instrument for psychological autopsy studies.
      Low correlation in two of the algorithm steps for decision making may be due to
      the lack of accuracy of the questionnaire and should be improved.

PMID- 21188673
TI  - [Development and psychometric properties of a brief instrument to measure the
      stigma of aggressiveness in schizophrenia].
AB  - INTRODUCTION: Schizophrenia has been object of stigmatization throughout history.
      A critical component of stigma in schizophrenia is the perception that patients
      are extremely dangerous. The assessment of this concept in general population by
      the use of reliable and valid instruments will allow the development of programs
      aimed to reduce it. OBJECTIVE: To develop an assessment instrument of the public
      conception of aggressiveness in schizophrenia and to determine its reliability
      and validity in a community sample of Mexico City. METHOD: A total of 258
      subjects completed the Public Conception of Aggressiveness Questionnaire (CAQ)
      which is made up of a brief clinical vignette and specific questions that assess
      subjective conceptions about aggressiveness and mental disorders in patients with
      schizophrenia. RESULTS: More than 40.0% of the sample considered that the patient
      with schizophrenia is aggressive and dangerous. The CAQ had an adequate internal
      consistency (alpha=0.74). The results of the factorial analysis showed that the
      two factors that explained 61.0% of the variance. DISCUSSION: The items of CAQ
      showed two major areas that evaluate: a) perception of presentation of aggressive
      behaviors and, b) mental illness recognition and social aspects of the stigma of
      dangerousness. The CAQ is an instrument with adequate psychometric properties
      that could be useful to evaluate the perception of aggressiveness in
      schizophrenia among general population.

PMID- 21188674
TI  - Validation of the Spanish version of the PHQ-15 questionnaire for the evaluation
      of physical symptoms in patients with depression and/or anxiety disorders: DEPRE
      SOMA study.
AB  - OBJECTIVE: This work has aimed to validate the Spanish version of the PHQ-15
      questionnaire (Patient Health Questionnaire) for its use in patients with
      depression and/or and anxiety disorders. MATERIAL AND METHODS: An observational,
      cross-sectional study in which the PHQ-15 questionnaire (made up of 15 items on
      somatic symptoms) was administered in the outpatient psychiatric clinics to
      patients of 18 years or more, diagnosed of depression and/or anxiety disorder
      according to the DSM-IV criteria. Feasibility (percent of patients without
      response), reliability (in terms of internal consistency) and
      convergent/divergent validity compared to the MADRS scale (by correlational
      analysis), discriminant (with intragroup comparison) and predictive (by
      logistical regression). RESULTS: A total of 3362 evaluated patients were
      included. Of these, 65.5% were women, with a mean age of 45.6 years (18.0-90.0).
      The questionnaire was feasible (9.6% of patients lacking an answer to some item),
      and showed acceptable internal reliability (Cronbach's Alpha Coefficient =0.78)
      with adequate validity, with correlations with the MADRS scale between moderate
      and high (r=0.3-0.7) and differences between groups of patients. The factors
      associated to the profile type of the patient with relevant physical symptoms
      were: being a woman, having a background of depression and/or anxiety, anxiety
      according to the DSM-IV, any concomitant condition in general, and specifically
      hepatic-digestive and osteoarticular system affectation and, as protective
      factor, being 70 years of age or older. CONCLUSION: The PHQ-15 questionnaire in
      its Spanish version has been shown to be feasible, reliable and valid to evaluate
      somatic symptoms in patients with depression and/ or anxiety disorders in
      psychiatry.

PMID- 21188675
TI  - Sleep disorders in the adult population of Santiago of Chile and its association
      with common psychiatric disorders.
AB  - INTRODUCTION: Sleep disorders are a frequent problem and they are a usual reason
      of primary care consultation, because they cause a significant deterioration in
      the quality of life. Insomnia is the most common sleep disorder and it has a
      total prevalence in adults estimated of 19.1%, of whom 85% are chronic insomnia,
      which in turn is closely related to psychiatric disorders and even more it has
      been described as a depressive episode marker. AIMS: To characterize the Santiago
      adult population suffering from sleep disorders and analyze their statistical
      association with common mental disorders. METHODOLOGY: It corresponds to a
      secondary analysis of the survey "Common Mental Disorders in Santiago". A cross
      sectional survey that used as a sampling frame the adult population of Santiago
      aged between 16 to 64 years was carried out. A structured interview covering
      sociodemographic factors and the Revised Clinical Interview Schedule (CIS-R) to
      measure emotional symptoms, were applied. RESULTS: 3867 people representative of
      the adult population were evaluated (52.3% women, 47.7% men). The prevalence of
      sleep disorders was 26.3%. Sociodemographic risk factors, statistically
      significants, were detected like female gender, unemployed seeking employment,
      the presence of a common mental disorder, alcohol and drugs consumption in the
      last month, among others. CONCLUSIONS: There is a high prevalence of sleep
      disorders among the population of Santiago; this is closely associated to female
      gender, social disadvantages and potently to the presence of a common mental
      disorder.

PMID- 21188676
TI  - Minor physical anomalies and schizophrenia: literature review.
AB  - Many authors view schizophrenia as a neurodevelopmental disorder. Knowledge of
      whether patients have morphologic variants that occur during the development of
      different anatomic areas of the brain and an understanding of the relation
      between such variants and brain development or prenatal exposure to possible
      noxae could provide clues about the events that lead to schizophrenia.
      Nonspecific morphologic variants that occur during the first and second
      trimesters of gestation, which are known as minor physical anomalies (MPA) and
      can be used as disease risk markers insusceptible persons, have been related with
      schizophrenia,independently of the anatomic region where they occur. The
      importance of these anomalies in relation to schizophrenia is that they may
      reflect a substrate (schizotaxia) that is either inherited or acquired as a
      consequence of injury(ies)that would result in the disease in susceptible
      persons. This idea is also supported by indirect evidence provided by family
      studies, among others. On the other hand, the role of MPA in other
      neurodevelopmental orders is similar to the role proposed in schizophrenia.

PMID- 21188677
TI  - Chronic hallucinatory psychosis. A case report.
AB  - Chronic hallucinatory psychosis is a clinical picture described by Ballet in
      1912. Together with paraphrenia and paranoia, it forms a part of the chronic
      delusions that describes the French nosology separately from schizophrenia. It is
      characterized by the presence of mental automatism, chronic hallucinations and
      secondary delusions. This is a fairly uncommon clinical picture in our setting
      and is often confused with other pictures. We report a case of a 52-year-old
      woman and we discuss various clinical and diagnostic issues related to the
      disturbance.

PMID- 21188678
TI  - Clinical characteristics and legal consequences of violent behavior: a case of
      bipolar disorder.
AB  - The main subject of criminal proceedings is that of criminal responsibility, from
      this point of view bipolar disorders sometimes seem to be a neglected subject in
      legal scholarship. Yet they may affect decision-making across the spectrum of the
      law, especially when manic and psychotic symptoms are implicated. This case
      studies a 37-year-old woman, diagnosed with bipolar affective in disorder, who
      attacked the neighbour of her ex-husband during a manic episode with psychotic
      symptoms. Two groups of those psychotic symptoms are especially remarkable:
      delusions and experiences of influences playing on her body and thought insertion
      (threat/control-override symptoms). Hostility against her ex-husband was also
      implicated in the attack. Researchers have pointed all those symptoms as
      important predictors of violence, and they have determinant legal correlates.

PMID- 21188679
TI  - Retrospective analysis of stimulant abuse cases reported to the Swiss
      Toxicological Information Centre during 1997-2009.
AB  - STUDY AIM: To describe characteristics of stimulant abuse and toxicity. METHOD:
      We conducted a retrospective analysis of cases of exposure to cocaine,
      amphetamines (amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine
      [MDMA]) and methylphenidate reported to the Swiss Toxicological Information
      Centre between 1997 and 2009. RESULTS: There were 667 reports for cocaine, 147
      for amphetamine, 41 for methamphetamine, 433 for MDMA, and 122 for
      methylphenidate. Detailed outcome data were available in 546 (39%) of all
      reported cases. Exposure to amphetamine or MDMA commonly resulted in mild to
      moderate toxicity, but severe toxicity was seen in approximately 15% of reported
      cocaine and MDMA exposures with a known medical outcome. Frequently observed
      clinical signs and symptoms included tachycardia, arterial hypertension, nausea,
      agitation, and panic. Amphetamine and MDMA exposures were seen in a younger
      population and were mainly reported at weekends, while cocaine users were older
      and exposures occurred proportionally more frequently on weekdays. Parenteral
      drug use and co-use of heroin was more frequent in cocaine users than in those
      using other stimulants. There has been an increase in reports of non-medical use
      of methylphenidate in recent years, indicating a need for further studies of
      abuse of prescription stimulants. CONCLUSION: Stimulant abuse is associated with
      major toxicity in approximately 15% of reported cases with a known medical
      outcome. Amphetamine and MDMA users differed from cocaine users in terms of user
      characteristics, time of use and medical complications. Non-medical use of
      prescription stimulants such as methylphenidate needs attention.

PMID- 21188680
TI  - Management of secondary hyperparathyroidism in Italy: results of the Italian FARO
      survey.
AB  - AIMS: In recent years, treatment options for secondary hyperparathyroidism (SHPT)
      have increased (e.g., paricalcitol, calcimimetics). To determine the impact these
      new treatments have on achieving K/DOQI targets, an observational, prospective
      survey was undertaken. METHODS: Four 6-month time-spaced surveys of 2,637
      patients in 28 Italian dialysis units were performed. Patient demographic
      information; use of vitamin D or calcimimetics; and changes in parathyroid
      hormone (PTH), calcium (Ca) and phosphate (P) levels were evaluated. RESULTS:
      Over the course of the survey, use of calcitriol decreased (from 62.1% at
      baseline to 44.5% at month 18; p<0.001), while use of paricalcitol (from 19.9% to
      36.9%; p<0.001) and calcimimetics (from 6.4% to 10.8%; p<0.001) increased. This
      was associated with a decrease in mean PTH values (from 310.3 +/- 292.4 pg/mL at
      baseline to 279.5 +/- 250.1 pg/mL at month 18; p=0.0002), while mean Ca and P
      remained steady. The percentage of patients achieving K/DOQI ranges for PTH (from
      26.8% at baseline to 32.0% at month 18, p<0.001), Ca (from 50.4% at baseline to
      55.9% at month 18, p<0.001) and the 3 targets combined (PTH, Ca and P; from 8.8%
      at baseline to 11.5% at month 18, p=0.003) significantly increased (p<0.05).
      Despite the introduction of newer agents, two thirds of patients did not achieve
      target levels. CONCLUSIONS: Increased awareness and newer treatment options for
      chronic kidney disease patients with SHPT have changed treatment policy and
      number of patients achieving K/DOQI target levels in Italy. However, the majority
      of patients did not meet the target ranges, suggesting that new drugs and
      strategies are still warranted for optimal management of SHPT in chronic kidney
      disease.

PMID- 21188681
TI  - Visual and optical coherence tomography outcomes of intravitreal bevacizumab and
      ranibizumab in inflammatory choroidal neovascularization secondary to punctate
      inner choroidopathy.
AB  - PURPOSE: Choroidal neovascular membranes (CNV) are the major cause of visual loss
      in punctate inner choroidopathy (PIC), an idiopathic inflammatory condition
      predominantly affecting young, myopic women. We present a case series of 9
      patients with CNV associated with PIC, treated with intravitreal anti-vascular
      endothelial growth factor agents. METHODS: This is a retrospective case series of
      9 patients treated with either intravitreal bevacizumab or ranibizumab for
      inflammatory CNV secondary to PIC. Initial and posttreatment converted logMAR
      visual acuity, fundus fluorescein angiograms (FFA), optical coherence tomography
      (OCT), previous and concurrent treatments, and side effects were recorded.
      Informed consent for treatment was obtained from each patient. RESULTS: Nine
      patients (8 female, 1 male) with an average age of 34.4 years were treated for an
      average of 14.9 months. Six patients were treated with bevacizumab, and 3 with
      ranibizumab, with a mean of 2.34 injections per year. The mean visual acuity gain
      for the whole group of 9 patients was 0.26 converted logMAR units (Wilcoxon
      signed-rank test, p<0.015). Eight patients remained stable or had visual
      improvement at final follow-up, with a mean gain of 0.36 converted logMAR units.
      Only one patient's vision deteriorated (loss of 0.48 converted logMAR units).
      Concomitant short courses of oral corticosteroid were used in 3 of the 9
      patients. CONCLUSIONS: Over a 1-year period, bevacizumab and ranibizumab can be
      safely and successfully used to treat inflammatory CNV secondary to PIC, avoiding
      the need for systemic immunosuppression in the majority of patients.

PMID- 21188682
TI  - Surgical treatment of ocular toxocariasis: anatomic and functional results in 45
      patients.
AB  - PURPOSE: To evaluate the anatomic and functional outcome after surgery in
      patients with complicated ocular toxocariasis. METHODS: A retrospective review of
      the medical records of pediatric patients who underwent a surgical procedure for
      ocular toxocariasis from July 1990 to January 2005. Patients with postoperative
      follow-up shorter than 6 months were excluded from the study. Best-corrected
      visual acuity (BCVA) was arbitrarily divided into 5 groups: 1) no light
      perception (NLP); 2) light perception (LP) and hand motion (HM); 3) finger
      counting (FC) to 20/400; 4) 20/300 to 20/60; and 5) 20/50 to 20/20. RESULTS:
      Forty-five patients with a mean age of 8.1 years (range 6-10) were included in
      the study. The ocular toxocariasis presentation most commonly encountered was
      peripheral granuloma (38%). Twenty-one eyes presented with BCVA in the LP/HM
      group, 18 (40%) eyes in the FC to 20/400 group, 5 (12%) eyes in the 20/300 to
      20/60 group, and 1 (5%) eye in the 20/50 to 20/20 group. The most common surgical
      procedure was pars plana vitrectomy (PPV) in 58% of the eyes. Four eyes (9%)
      presented with postoperative BCVA of NLP, 2 eyes (4%) in the LP/HM group, 12 eyes
      (27%) in the FC to 20/400 group, 19 eyes (42%) in the 20/300 to 20/60 group, and
      8 eyes (18%) in the 20/50 to 20/20 group. CONCLUSIONS: Surgical treatment of
      severe ocular complications secondary to toxocara infections results in
      satisfactory anatomic results and may improve the overall visual outcome of these
      patients.

PMID- 21188683
TI  - Male breast carcinoma metastatic to the choroid: report of 3 cases and review of
      the literature.
AB  - PURPOSE: To describe breast cancer as a source of choroidal metastasis in men and
      highlight the diagnostic and treatment modalities. METHODS: Retrospective,
      noncomparative case series of male patients with breast cancer metastatic to the
      choroid. A literature review of the previously reported cases was also conducted.
      RESULTS: Three cases of breast cancer metastatic to the choroid in male patients
      from one institution are described. All 3 patients eventually underwent treatment
      with radiotherapy. CONCLUSIONS: Breast cancer is a rare cause of choroidal
      metastases in men. Radiotherapy is effective as a palliative treatment for
      choroidal metastases.

PMID- 21188684
TI  - Ocular surface reconstruction using amniotic membrane following excision of
      conjunctival and limbal tumors.
AB  - PURPOSE: To report the clinical results of patients treated by preserved human
      amniotic membrane transplantation (AMT) following the removal of conjunctival and
      limbal tumors. METHODS: Retrospective noncomparative interventional case series
      of 9 patients (9 eyes) who underwent AMT after removal of conjunctival and limbal
      tumors with lesion-free margins and perilesional cryotherapy. RESULTS: The
      excised tumors were histopathologically examined and included 2 squamous cell
      carcinomas, 2 papillomas, and 5 nevi. Bulbar conjunctiva was involved in all of
      the eyes, limbus and cornea in 7 and 3 eyes, respectively. The mean extent of the
      limbal involvement was 4 clock hours (range 2-9, SD 2.4); the average diameter of
      the base of the tumor was 12.8 mm (range 10-20, SD 4.4). The mean follow-up time
      was 38 months (range 13-60, SD 15). No surgical or early postoperative
      complications were observed. In all eyes, complete healing of the tissue defect
      occurred, resulting in a stable, wet, and noninflamed epithelium. All eyes
      demonstrated a smooth ocular surface except one with a clinically insignificant
      symblepharon after the excision of a squamous cell carcinoma. Superficial
      peripheral corneal vascularization and opacification as a sign of partial limbal
      stem cell deficiency developed in 2 eyes. In one case, a recurrence of
      conjunctival papilloma was diagnosed after a 3-year follow-up. CONCLUSIONS:
      Amniotic membrane transplantation is an effective method of reconstruction
      following a conjunctival and limbal tumor excision and cryotherapy of surgical
      wound margins. In most cases, complete healing of an ocular surface can be
      achieved without any clinically significant complications.

PMID- 21188685
TI  - Identification of a novel mutation in the PTCH gene in a patient with Gorlin
      Goltz syndrome with unusual ocular disorders.
AB  - PURPOSE: To document the clinical, functional, and in vivo microanatomic
      characteristics of a patient with Gorlin-Goltz syndrome with a novel nonsense
      mutation in PTCH (patched). METHODS: Optical coherence tomography (OCT),
      fluorescein angiography, electrophysiologic testing, visual field, magnetic
      resonance imaging, and mutation screening of PTCH gene. RESULTS: Visual acuity
      was 20/20 in the right eye and 20/25 in the left. Fundus examination revealed
      myelinated nerve fibers in the left eye and bilateral epiretinal membranes with
      lamellar macular hole also documented with macular OCT. A reduction of the
      retinal nerve fiber layers in both eyes was found with fiber nervous OCT.
      Fluorescein angiography showed bilaterally foveal hyperfluorescence and the
      visual field revealed inferior hemianopia in the right eye. Pattern visual evoked
      potentials registered a reduction of amplitude in both eyes and latency was
      delayed in the left eye. Pattern electroretinogram showed a reduction in P50 and
      N95 peak time and a delay in P50 peak time in the left eye. Flash
      electroretinogram was reduced in rod response, maximal response, and oscillatory
      potentials in both eyes. Cone response was normal and 30-Hz flicker was slightly
      reduced in both eyes. Mutation screening identified a novel nonsense mutation in
      PTCH. CONCLUSIONS: A novel nonsense mutation in the PTCH gene was found. We
      report the occurrence of epiretinal membranes and the persistence of myelinated
      nerve fibers. Electrophysiologic and visual field alterations, supporting a
      neuroretinal dysfunction, were also documented.

PMID- 21188687
TI  - Direct nanopatterning of silsesquioxane/poly(ethylene glycol) blends with high
      stability and nonfouling properties.
AB  - A free-radical-polymerizable SSQ/PEG blend with direct patternability has been
      proposed as an ideal nonfouling material for nanostructure-based biomedical
      applications. Cured SSQ/PEG networks show an UV transparency of >90% at 365 nm,
      high resistance to organic/aqueous solutions, hydrophilicity and Young's moduli
      of 1.898-2.815 GPa. SSQ/PEG patterns with 25-nm linewidths, 25-nm spacing, and an
      aspect ratio of 4:1 were directly fabricated on transparent substrates by UV
      embossing, and cured SSQ/PEG networks with long-term stability under chemical,
      thermal, and biological stress showed strong resistance to the nonspecific
      adsorption of biomolecules. These characteristics may offer a new strategy for
      the development of a number of medical nanodevice applications such as labs-on-a
      chip.

PMID- 21188686
TI  - Self-assembly strategy for the preparation of polymer-based nanoparticles for
      drug and gene delivery.
AB  - Nanoparticulate drug-delivery systems have attained much importance because of
      their injectable property, the possibility to achieve passive targeting and
      active targeting, and unique advantages to realize stimuli tailored delivery.
      Molecular self-assembly is a powerful method for fabricating polymer-based
      nanoparticles, which involves various driving forces, such as hydrophobic
      interactions, electrostatic interactions, stereocomplexation, host/guest
      interactions and hydrogen bonding. By fine tuning one or many types of these
      interactions, self-assemblies with a wide range of structures and functions could
      be fabricated. In this article, recent developments in different self-assembly
      strategies for the preparation of polymer-based nanoparticulate delivery systems
      are discussed.

PMID- 21188688
TI  - Advances in mucoadhesion and mucoadhesive polymers.
AB  - Mucoadhesion is the ability of materials to adhere to mucosal membranes in the
      human body and provide a temporary retention. This property has been widely used
      to develop polymeric dosage forms for buccal, oral, nasal, ocular and vaginal
      drug delivery. Excellent mucoadhesive properties are typical for hydrophilic
      polymers possessing charged groups and/or non-ionic functional groups capable of
      forming hydrogen bonds with mucosal surfaces. This feature article considers
      recent advances in the study of mucoadhesion and mucoadhesive polymers. It
      provides an overview on the structure of mucosal membranes, properties of mucus
      gels and the nature of mucoadhesion. It describes the most common methods to
      evaluate mucoadhesive properties of various dosage forms and discusses the main
      classes of mucoadhesives.

PMID- 21188689
TI  - Strong in biomaterials and polymer science.

PMID- 21188696
TI  - Chemo-physical and biological evaluation of poly(L-lysine)-grafted chitosan
      copolymers used for highly efficient gene delivery.
AB  - For the success of non-viral gene delivery, it is of great importance to develop
      gene vectors with high efficiency but low toxicity. We demonstrate that PLL
      grafted chitosan copolymers combine the advantages of PLL with its good pDNA
      binding ability and of chitosan with its good biocompatibility. The chemo
      physical properties of the prepared Chi-g-PLL copolymers are thoroughly
      characterized. The in vitro transfection study shows that the copolymers have a
      much higher gene transfer ability than the starting materials chitosan and PLL. A
      positive correlation between PLL chain lengths and transfection efficiency of the
      copolymers is found. Our results suggest that these novel Chi-g-PLL copolymers
      are good candidates for gene delivery in vivo.

PMID- 21188699
TI  - A healthy diagnosis for materials science.

PMID- 21188702
TI  - Magnificent seven.

PMID- 21188710
TI  - Significance of the International Year of Chemistry 2011.

PMID- 21188718
TI  - Multicolor polymer-dispersed liquid crystal.

PMID- 21188720
TI  - Protein-protein interactions: making sense of networks via graph-theoretic
      modeling.
AB  - The emerging area of network biology is seeking to provide insights into
      organizational principles of life. However, despite significant collaborative
      efforts, there is still typically a weak link between biological and
      computational scientists and a lack of understanding of the research issues
      across the disciplines. This results in the use of simple computational
      techniques of limited potential that are incapable of explaining these complex
      data. Hence, the danger is that the community might begin to view the topological
      properties of network data as mere statistics, rather than rich sources of
      biological information. A further danger is that such views might result in the
      imposition of scientific doctrines, such as scale-free-centric (on the modeling
      side) and genome-centric (on the biological side) opinions onto this area. Here,
      we take a graph-theoretic perspective on protein-protein interaction networks and
      present a high-level overview of the area, commenting on possible challenges
      ahead.

PMID- 21188735
TI  - Posterior brain in fetuses with open spina bifida at 11 to 13 weeks.
AB  - OBJECTIVE: To measure the changes in the posterior fossa in first-trimester
      fetuses with open spina bifida (OSB). METHODS: The brain stem diameter and brain
      stem to occipital bone (BSOB) diameter were measured in stored images of the mid
      sagittal view of the fetal face at 11(+0) to 13(+6) weeks from 30 fetuses with
      OSB and 1000 normal controls. RESULTS: In the control group, the brain stem and
      BSOB diameter increased significantly with crown-rump length (CRL) and the brain
      stem to BSOB ratio decreased. In the spina bifida group, the brain stem diameter
      was above the 95th percentile of the control group in 29 (96.7%) cases, the BSOB
      diameter was below the 5th percentile in 26 (86.7%) and the brain stem to BSOB
      ratio was above the 95th percentile in all cases. CONCLUSIONS: At 11 to 13 weeks
      the majority of fetuses with OSB have measurable abnormalities in the posterior
      brain.

PMID- 21188737
TI  - Prediction of spontaneous preterm delivery from endocervical length at 11 to 13
      weeks.
AB  - OBJECTIVE: To define the potential value of endocervical length at 11 to 13
      weeks' gestation in the prediction of spontaneous early delivery. METHOD: The
      lengths of the endocervix and cervico-isthmic complex were measured by
      transvaginal ultrasound at 11 to 13 weeks in singleton pregnancies, including
      1492 that subsequently delivered after 34 weeks and 16 (1.1%) who had spontaneous
      delivery before 34 weeks. In 1320 of the cases, the measurements were repeated at
      20 to 24 weeks. RESULTS: There were significant associations in the length of the
      endocervix and cervico-isthmic complex between 11 to 13 and 20 to 24 weeks (r =
      0.548, p < 0.0001 and r = 0.194, p < 0.0001), and the respective median lengths
      were 32.4 and 32.2 mm for the endocervix and 45.3 and 40.4 mm for the cervico
      isthmic complex. At 11 to 13 weeks in the early delivery group, compared to
      unaffected pregnancies, the median endocervical length was shorter (27.5 vs 32.5
      mm, p < 0.0001), but there was no significant difference in the length of the
      cervico-isthmic complex (41.4 vs 45.4 mm, p = 0.054). CONCLUSION: In the
      measurement of cervical length, the endocervix should be distinguished from the
      isthmus. The endocervical length at 11 to 13 weeks is shorter in pregnancies
      resulting in spontaneous delivery before 34 weeks than in those delivering after
      34 weeks.

PMID- 21188740
TI  - Emerging trends. Study finds low awareness level of HIV infection among MSM.

PMID- 21188741
TI  - Research to focus on HIV within U.S. prison, jail systems.

PMID- 21188742
TI  - Prisons.  Inmate's claim of HIV transmission dismissed as frivolous.

PMID- 21188743
TI  - Employment.  Plan abused its discretion by denying man disability benefits.

PMID- 21188745
TI  - Tumor-specific therapy based on BRCA1/2 mutation status.

PMID- 21188744
TI  - Festschrift in honor of the 75th birthday of Professor Wolfgang Barz.

PMID- 21188746
TI  - Migraine: Familial migraine with aura is associated with a mutation in the TRESK
      potassium channel.

PMID- 21188747
TI  - Stroke: Imaging improves the predictive utility of ABCD2.

PMID- 21188748
TI  - Epilepsy: A new therapeutic strategy in epileptic seizure suppression.

PMID- 21188749
TI  - Motor neuron disease: Misfolded wild-type SOD1 may link sporadic and familial
      ALS.

PMID- 21188750
TI  - Abstracts of the International Society for Environmental Epidemiology (ISEE) 22nd
      Annual Conference. Seoul, Korea. August 28-September 1, 2010.

PMID- 21188751
TI  - CPR in assisted living: not as simple as it seems.

PMID- 21188752
TI  - Positive frequency-dependent selection on warning color in Alpine leaf beetles.
AB  - Muller's theory of warning color and mimicry, despite forming a textbook example
      of frequency-dependent selection, has rarely been demonstrated in the wild. This
      may be largely due to the practical and statistical difficulties of measuring
      natural selection on mobile prey species. Here we demonstrate that this selection
      acts in alpine beetle communities by using tethered beetles exposed to natural
      predators. Oreina gloriosa leaf beetles (Coleoptera: Chrysomelidae) possess
      chemical defense in the form of cardenolides, accompanied by what appears to be
      warning color in bright metallic blues and greens. Individuals that match the
      locally predominant color morph have increased survival, with odds of week-long
      survival increased by a factor of 1.67 over those that do not match. This
      corresponds to selection of 13% against foreign morphs. Such selection, acting in
      concert with variation in community composition, could be responsible for
      geographic variation in warning color. However, in the face of this purifying
      selection, the within-population polymorphism seen in many Oreina species remains
      paradoxical.

PMID- 21188753
TI  - Abstracts of the 1st Asia-Pacific Osteoporosis Meeting. December 10-13, 2010.
      Singapore.

PMID- 21188754
TI  - Endometriosis.

PMID- 21188755
TI  - Correction of posttraumatic kyphosis of the thoracolumbar spine  with modified
      pedicle subtraction osteotomy.

PMID- 21188757
TI  - Improving medication safety in older adults. An interview with Dr. Kellie L.
      Flood, by Scott Bugg.

PMID- 21188756
TI  - Bridging the Digital Divide for urban seniors: community partnership.
AB  - Computers and the Internet offer older adults resources for improving health. For
      many older adults, the "Digital Divide" (the social, economic, and demographic
      factors that exist between individuals who use computers and those who do not) is
      a barrier to taking advantage of these resources. Bridging the Digital Divide by
      making computers and the Internet more accessible and making online health
      information more usable for older adults has the potential to improve health of
      older adults. This article describes a strategy for closing the Digital Divide
      for urban seniors through the formation of a community- university partnership
      with the goal of improving health and well-being through the use of online health
      information.

PMID- 21188758
TI  - Hybrid strategy for correction and T3-sacrum posterior fusion in a severe
      neuropathic spinal deformity.

PMID- 21188759
TI  - Correction of post-traumatic hyperkyphosis of the upper thoracic spine by
      multiple Chevron osteotomies.

PMID- 21188760
TI  - Winner of the Wakley prize 2010.

PMID- 21188761
TI  - Tackling loneliness in the holidays.

PMID- 21188762
TI  - What you need to know about Clopidogrel.  This drug helps to prevent the blood
      clots that can cause heart attacks and stroke.

PMID- 21188763
TI  - The older Parkinson's disease drugs pergolide and cabergoline have been linked to
      heart problems.  Are there any new Parkinson's drugs which are safer for patients
      with heart risks?

PMID- 21188765
TI  - Findings of research misconduct.

PMID- 21188764
TI  - Is there an age limit for valve replacement? I am 79 and have a leaky aortic
      valve, but am in otherwise pretty good health.

PMID- 21188766
TI  - Expanded spectrum of oculo-auriculo-vertebral spectrum with imperforate anus in a
      male patient who is negative for SALL1 mutations.

PMID- 21188767
TI  - Disease awareness and knowledge in caregivers of children who had surgery for
      cystic hydatid disease in Lima, Peru.
AB  - Cystic hydatid disease (CHD) is a common cause of lung and liver disease
      worldwide. Despite Peru being highly endemic, information about the level of
      knowledge is scarce and poor. A telephone survey was applied to assess the
      knowledge in the caregivers of patients treated for CHD at a paediatric hospital
      at Lima, Peru. Of the 26 contacted families, only 5 (20%) answered correctly all
      seven questions. A higher education degree was associated with correct answers (P
      = 0.002). Most respondents (17, 65%) incorrectly identified the etiologic agent
      and mode of transmission. Lact of knowledge is likely a major contributor to
      maintain the endemicity of disease in Peru.

PMID- 21188768
TI  - p53, transcriptional, and drug sensitivity: fresh perspectives on an old
      activity.

PMID- 21188769
TI  - Prostate cancer: Risk stratification of PSA-based screening.

PMID- 21188770
TI  - Prostate cancer: Contemporary aDt usage reflects established benefit.

PMID- 21188771
TI  - Adding telaprevir improves cure rate in patient with HCV infection.

PMID- 21188772
TI  - UCLA gets $4.6M grant to study HIV among men in jail.

PMID- 21188773
TI  - Stones: Safety guidewire unnecessary during flexible ureteroscopy for routine
      cases of nephrolithiasis.

PMID- 21188774
TI  - Prostate cancer: Cabazitaxel boosts post-docetaxel survival.

PMID- 21188775
TI  - Kidney cancer: Are we overclassifying renal cancer?

PMID- 21188776
TI  - Pediatrics: 20 years of hypospadias repair-yet still no consensus.

PMID- 21188777
TI  - Bladder cancer: Does augmentation cystoplasty increase the risk of bladder
      cancer?

PMID- 21188778
TI  - Incontinence: Trigonal injection of botulinum toxin-A improves outcome.

PMID- 21188779
TI  - Psychogenic nonepileptic "seizures " or "attacks"? It's not just semantics:
      attacks: psychogenic nonepileptic "seizures" or "attacks"? It's not just
      semantics: seizures.

PMID- 21188780
TI  - Psychogenic nonepileptic "seizures " or "attacks"? It's not just semantics:
      attacks: psychogenic nonepileptic "seizures" or "attacks"? It's not just
      semantics: seizures.

PMID- 21188781
TI  - Psychogenic nonepileptic "seizures " or "attacks"? It's not just semantics:
      attacks: psychogenic nonepileptic "seizures" or "attacks"? It's not just
      semantics: seizures.

PMID- 21188783
TI  - Saccadic latency in deterministic environments: getting back on track after the
      unexpected happens.
AB  - Saccadic latencies are commonly used to study decision mechanisms. For instance,
      in a random sequence, saccadic latency to a target depends on how frequently it
      has recently appeared. However, frequency is not the only factor that determines
      probability. Here we presented targets to the left or right, either in random
      sequences or in repeating patterns. Although the frequency of appearing on a
      given side was identical in each case, latencies for the low-frequency side were
      significantly shorter for repeating patterns than in random sequences, showing
      that the system can respond to the deterministic probabilities in such patterns.
      We then disrupted our patterns episodically, recommencing at a random starting
      position in the sequence. This significantly increased the latency, which
      remained high until the low-frequency target in the sequence reappeared, implying
      that the oculomotor system makes strategic use of low-frequency--but high
      information--events to determine the phase of repeating sequences. The
      deterministic sequences of events in our patterns represent a simple model for
      the habitual sequences of actions commonly performed in daily life, which, when
      disrupted, require the engagement of a higher level problem-solving strategy to
      return us to our previous automated sequence as quickly as possible.

PMID- 21188784
TI  - Perceived slant of binocularly viewed large-scale surfaces: a common model from
      explicit and implicit measures.
AB  - It is known that the perceived slants of large distal surfaces, such as hills,
      are exaggerated and that the exaggeration increases with distance. In a series of
      two experiments, we parametrically investigated the effect of viewing distance
      and slant on perceived slant using a high-fidelity virtual environment. An
      explicit numerical estimation method and an implicit aspect-ratio approach were
      separately used to assess the perceived optical slant of simulated large-scale
      surfaces with different slants and viewing distances while gaze direction was
      fixed. The results showed that perceived optical slant increased logarithmically
      with viewing distance and the increase was proportionally greater for shallow
      slants. At each viewing distance, perceived optical slant could be approximately
      fit by linear functions of actual slant that were parallel across distances.
      These linear functions demonstrated a fairly constant gain of about 1.5 and an
      intercept that increased logarithmically with distance. A comprehensive three
      parameter model based on the present data provides a good fit to a number of
      previous empirical observations measured in real environments.

PMID- 21188785
TI  - SOPHE at sixty: the best is yet to come: 2009 SOPHE Presidential Address.

PMID- 21188786
TI  - Antiepileptic drugs and suicide attempts in patients with bipolar disorder-reply.

PMID- 21188787
TI  - Brain-derived neurotrophic factor gene polymorphisms: influence on treatment
      response phenotypes of major depressive disorder.
AB  - Brain-derived neurotrophic factor (BDNF), a member of the nerve growth factor
      family of neurotrophins, has pivotal roles in neuronal survival, proliferation,
      and synaptic plasticity in the brain. Both clinical and pharmacological studies
      have implicated the common single nucleotide polymorphism (SNP) at position 196,
      Val66Met in the pathophysiology of major depressive disorder (MDD), and
      antidepressant response. However, inconsistent results were found between
      Val66Met (rs6265) polymorphism and treatment response phenotypes in genetic
      association studies. The functional Val66Met polymorphism and seven other tagging
      SNP markers selected to capture the major allelic variations across BDNF locus
      were analyzed in depressed patients, treated with antidepressants, and 76 control
      patients. Two hundred and six patients with Diagnostic and Statistical Manual of
      Mental Disorders-IV MDD were recruited for this study and genotyped for eight
      BDNF tagging SNPs (rs11030096, rs925946, rs10501087,rs6265, rs12273363, rs908867,
      rs1491850, and rs1491851)to investigate the functional impact of
      genotypes/haplotypes in the susceptibility of depression and on treatment
      response. None of the eight SNPs, including the rs6265, were significantly
      associated with MDD after permutation correction. However, we found an
      association for rs10501087, rs6265 with nonresponse to antidepressant treatment
      (corrected permutation P:0.03599; 0.0399 and power: 0.1420; 0.1492,
      respectively).Analysis of each two-marker, three-marker, and four-marker sliding
      window haplotypes showed significance in haplotype combinations. Especially
      rs10501087 (C), rs6265 (A), and rs149,1850 (C) together or with the other SNP
      haplotypes showed a similar pattern in all treatment response phenotypes. Despite
      the limited power of analysis, our results suggest that these three SNPs may play
      a role in antidepressant treatment response phenotypes in MDD.

PMID- 21188788
TI  - Image-guided thermal ablation. Preface.

PMID- 21188790
TI  - Photoswitchable triple hydrogen-bonding motif.
AB  - Photochromic bis(thiazol-4-yl)maleimides, displaying enhanced binding affinity to
      complementary melamine receptors in their ring-closed switching state, have been
      developed and could pave the way to light-responsive supramolecular assemblies.

PMID- 21188789
TI  - Vascular KCNQ channels in  humans: the sub-threshold  brake that regulates 
      vascular tone?
AB  - Contraction of arterial smooth muscle cells results in vasoconstriction, which in
      turn reduces blood flow and increases blood pressure. There has been a great deal
      of interest in understanding the ionic mechanisms that regulate smooth muscle
      contraction, in part because ion channels represent potential pharmacological
      targets for therapies directed towards cardiovascular diseases and other
      conditions. Potassium channels have been recognized for their roles in
      maintaining or stabilizing negative membrane voltages. Activation of potassium
      channels opposes opening of voltage-sensitive calcium channels which conduct
      calcium ions into the smooth muscle cells to stimulate contraction. KCNQ
      potassium channels were recently discovered in arterial smooth muscle cells from
      rats and mice. These channels have distinctive pharmacological and biophysical
      characteristics that have led them to be implicated as important regulators of
      membrane voltage and as novel pharmacological targets for modulation of vascular
      contractility. In this issue of British Journal of Pharmacology, Ng et al.,
      extend the findings from rodent models to the human vasculature and establish
      that KCNQ channels also regulate constriction of human arteries. The findings
      have important implications for the use of pharmacological KCNQ channel
      modulators to treat human diseases.

PMID- 21188791
TI  - [Communication and ethics in the hospital].

PMID- 21188792
TI  - [Professional services for the infant and his family].

PMID- 21188793
TI  - Another step towards understanding hemophilia A molecular pathogenesis.

PMID- 21188794
TI  - ADAMTS-13: double trouble for von Willebrand factor.

PMID- 21188795
TI  - Substance abuse among registered nurses.
AB  - The stressful conditions under which nurses work, due in part to the nursing
      shortage, are among the risk factors that contribute to nurses' abuse of illicit
      drugs. Nurses differ from the general population in that they work in an
      environment where they not only have access to controlled substances, but also
      are exposed to death and dying, the stress of which can increase the risk of drug
      abuse. However, practicing while impaired places patients' lives at risk and
      decreases staff morale.

PMID- 21188796
TI  - Integrating primary care with occupational health services: a success story.
AB  - This article describes the process used by a large U.S. manufacturing company to
      successfully integrate full-service primary care centers at two locations. The
      company believed that by providing employees with health promotion and disease
      prevention services, including screening, early diagnosis, and uncomplicated
      illness treatment, its health care costs could be significantly reduced while
      saving employees money. To accurately demonstrate the cost-effectiveness of
      adding primary care to existing occupational health services, a thorough
      financial analysis projected the return on investment (ROI) of the program.
      Decisions were made about center size, the scope of services, and staffing. A
      critical part of the ROI analysis involved evaluating employee health claim data
      to identify the actual cost of health care services for each center and the
      projected costs if the services were provided on-site. The pilot initiative
      included constructing two on-site health center facilities staffed with primary
      care physicians, nurse practitioners, physical therapists, and other health care
      professionals. Key outcome metrics from the pilot clinics exceeded goals in three
      of four categories. In addition, clinic use after 12 months far exceeded
      benchmarks for similar clinics. Most importantly, the pilot clinics were
      operating with a positive cash flow within the first year and demonstrated an
      increasingly positive ROI.

PMID- 21188798
TI  - Tools for assessing nausea, vomiting, and retching.
AB  - BACKGROUND: Chemotherapy-induced nausea, vomiting, and retching are recognized as
      having an impact on patients' overall physical well-being, quality of life, and
      treatment decisions. Although there are many tools available to measure aspects
      of these symptoms, few offer a complete and concise clinical assessment.
      OBJECTIVE: The purpose of this article was to provide a comprehensive overview of
      the various instruments available for the assessment of cancer-related nausea,
      vomiting, and retching. Analysis included symptoms measured, period evaluated,
      type of questions posed, and aspects of each symptom measured. METHODS: Searches
      were conducted to find relevant articles using nationally recognized oncology Web
      sites and 4 electronic databases including PubMed, MEDLINE/CINAHL and
      CINAHL/EBSCO, and Cochrane. RESULTS: This review includes a total of 25
      instruments that were identified as meeting the inclusion criteria of having been
      developed, or adapted, for the adult population, with an oncology focus.
      CONCLUSION: The ideal instrument would include measurement of all 3 symptoms
      while remaining clear, concise, and clinically relevant. IMPLICATIONS FOR
      PRACTICE: Although only 1 instrument came close to meeting these criteria, this
      review provides nurses with specific information on a variety of instruments to
      assist providers in selecting the most appropriate instrument for their specific
      clinical setting. This comprehensive critique of instruments is important for
      nurses attempting to select a tool to guide optimum care for patients in the
      clinical setting.

PMID- 21188797
TI  - A regulator of Dscam mutually exclusive splicing fidelity.
AB  - The Down syndrome cell adhesion molecule (Dscam) gene has essential roles in
      neural wiring and pathogen recognition in Drosophila melanogaster. Dscam encodes
      38,016 distinct isoforms via extensive alternative splicing. The 95 alternative
      exons in Dscam are organized into clusters that are spliced in a mutually
      exclusive manner. The exon 6 cluster contains 48 variable exons and uses a
      complex system of competing RNA structures to ensure that only one variable exon
      is included. Here we show that the heterogeneous nuclear ribonucleoprotein hrp36
      acts specifically within, and throughout, the exon 6 cluster to prevent the
      inclusion of multiple exons. Moreover, hrp36 prevents serine/arginine-rich
      proteins from promoting the ectopic inclusion of multiple exon 6 variants. Thus,
      the fidelity of mutually exclusive splicing in the exon 6 cluster is governed by
      an intricate combination of alternative RNA structures and a globally acting
      splicing repressor.

PMID- 21188799
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system. Systemic hypertension--a "ratologist"
      point of view.

PMID- 21188800
TI  - Basal internal anal sphincter tone, inhibitory neurotransmission, and other
      factors contributing to the maintenance of high pressures in the anal canal.
AB  - Maintenance of the basal tone in the internal anal sphincter (IAS) is critical
      for rectoanal continence. Effective evacuation requires a fully functional
      rectoanal inhibitory reflex (RAIR)-mediated relaxation of the IAS via inhibitory
      neurotransmission (INT). Systematic studies examining the nature of the INT in
      different species have identified nitric oxide (NO) as the major inhibitory
      neurotransmitter. However, other mediators such as vasoactive intestinal
      polypeptide (VIP), ATP, and carbon monoxide (CO) may also play species-specific
      role under certain experimental conditions. Measurements of the intraluminal
      pressures in the IAS along with the force of the isolated IAS tissues are the
      mainstay in the basic studies for the molecular mechanisms underlying the basal
      tone and in the nature of the INT. The identification of NO as the inhibitory
      neurotransmitter has led to major advances in the diagnosis and treatment of a
      number of rectoanal motility disorders associated with the IAS dysfunction.
      Besides the IAS, the high pressures in the anal canal are affected by the
      external anal sphincter (EAS) function, and its malfunction may also lead to
      rectoanal incontinence. Different approaches including biofeedback have been
      attempted to improve the EAS function, with variable outcomes. There is a dire
      need for the innovative ways to improve the week high pressures zone in the anal
      canal. This viewpoint focuses on two studies that extend the above concept of
      multiplicity of inhibitory neurotransmitters (Neurogastroenterol Motil 2011 23
      e11-25), and that high pressures in the anal canal can be improved by the EAS
      plication (Neurogastroenterol Motil 2011 23 70-5).

PMID- 21188802
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system. Sympathetic activation is the
      dominant contributor to systemic hypertension.

PMID- 21188803
TI  - Benfluorex: EU marketing authorisation finally withdrawn.
AB  - This amphetamine derivative was marketed for more than 30 years in France despite
      its lack of tangible efficacy in diabetes and hypertriglyceridaemia, and its
      potentially severe cardiovascular effects.

PMID- 21188804
TI  - Ketoprofen gel: severe photosensitisation.

PMID- 21188805
TI  - Injectable promethazine: gangrene.

PMID- 21188806
TI  - Lenalidomide: myocardial infarction.

PMID- 21188801
TI  - West Nile virus and its emergence in the United States of America.
AB  - Zoonotic West Nile virus (WNV) circulates in natural transmission cycles
      involving certain mosquitoes and birds, horses, humans, and a range of other
      vertebrates are incidental hosts. Clinical infections in humans can range in
      severity from uncomplicated WNV fever to fatal meningoencephalitis. Since its
      introduction to the Western Hemisphere in 1999, WNV had spread across North
      America, Central and South America and the Caribbean, although the vast majority
      of severe human cases have occurred in the United States of America (USA) and
      Canada. By 2002-2003, the WNV outbreaks have involved thousands of patients
      causing severe neurologic disease (meningoencephalitis and poliomyelitis-like
      syndrome) and hundreds of associated fatalities in USA. The purpose of this
      review is to present recent information on the epidemiology and pathogenicity of
      WNV since its emergence in North America.

PMID- 21188807
TI  - Olanzapine: sudden cardiac death, urinary incontinence.

PMID- 21188808
TI  - Entacapone: prostate cancer?

PMID- 21188809
TI  - Calcium dobesilate: neutropenia.

PMID- 21188810
TI  - Phloroglucinol: serious allergic reactions.

PMID- 21188811
TI  - Hypertension in adults without diabetes or complications: what is the target
      blood pressure?

PMID- 21188812
TI  - Hypertension in adults without diabetes or complications: what is the target
      blood pressure?

PMID- 21188813
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system. Sympathetic nervous system, plasma
      volume, and hypertension.

PMID- 21188814
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system. Systemic hypertension--involvement of
      the CNS to this complex puzzle.

PMID- 21188815
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system. Chronic activation of sympathetic
      nervous system and systemic hypertension--stress shows the way.

PMID- 21188816
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system.

PMID- 21188817
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system. Activation of the sympathetic nervous
      system is the dominant contributor to systemic hypertension.

PMID- 21188818
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system.

PMID- 21188819
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system.

PMID- 21188820
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system. The kidney is not always the target
      in neurogenic hypertension.

PMID- 21188821
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system. Carotid stimulation studies support a
      prominent role for the sympathetic nervous system.

PMID- 21188822
TI  - The changing landscape: a conversation with blood banking industry leaders.

PMID- 21188823
TI  - He's got a gun.

PMID- 21188824
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system.

PMID- 21188825
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system.

PMID- 21188826
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system. The dominant mechanism depends on
      individual circumstance.

PMID- 21188827
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system. Remodeling of central sympathetic
      circuits precedes the development of hypertension.

PMID- 21188828
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system. AT1 receptors in the kidney mediate
      the chronic hypertensive response to angiotensin II.

PMID- 21188829
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system. Intrarenal angiotensin II generation
      as a hypertensinogenic mechanism.

PMID- 21188831
TI  - Matthew Williams and his ketogenic diet.

PMID- 21188830
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system. Sympathetic activation: cause or
      consequence of hypertension?

PMID- 21188833
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system. The role of the sympathetic nervous
      system--influences of sex and aging.

PMID- 21188832
TI  - Discriminating cancer from noncancer tissue in the prostate by 3-dimensional
      proton magnetic resonance spectroscopic imaging: a prospective multicenter
      validation study.
AB  - OBJECTIVES: A prospective multicenter validation of the ability of 1H magnetic
      resonance spectroscopic imaging (MRSI) to distinguish cancer from noncancer
      tissues throughout the prostate with histopathology of the resected organ as the
      standard of reference. MATERIALS AND METHODS: Institutional review board approval
      was obtained for all centers and all participating patients and volunteers
      provided written informed consent. Ninety-nine patients and 10 age-matched
      volunteers from 8 participating centers underwent magnetic resonance imaging and
      3-dimensional MRSI with an endorectal coil at 1.5 T. Selected MRSI voxels were
      assigned to the peripheral zone (PZ), the central gland (CG), the periurethral
      area, and cancer tissue. Signal ratios of choline + creatine to citrate (CC/C) in
      spectra of these voxels were automatically calculated. Receiver operating
      characteristic curves were constructed to assess the accuracy by which this ratio
      can discriminate cancer from noncancer tissue. RESULTS: A total of 70% of voxels
      in noncancer tissue and 90% of voxels in cancer tissue passed the quality check
      of the automatically fitted spectra. The median CC/C was significantly different
      between any noncancer and cancer tissue (P < 0.0001), but not between the
      different contributing centers. CC/C increased with cancer focus size (P =0.0008)
      and certainty of voxel mapping to histopathologic cancer site (P 0.0001). The
      area under the receiver operating characteristic curve for discriminating voxels
      of cancer tissue from noncancer tissue was 0.88 (confidence interval: 0.84-0.92)
      in the PZ and 0.76 (confidence interval: 0.71- 0.81) in the CG.

PMID- 21188834
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system.

PMID- 21188835
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system. Obesity: a common prime mover of
      chronic activation of the sympathetic nervous system and the renin-angiotensin
      system in systemic hypertension?

PMID- 21188837
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system.

PMID- 21188838
TI  - Emerging and re-emerging animal viruses. Foreword.

PMID- 21188839
TI  - Breathing some air into the single-species vacuum: multi-species responses to
      environmental change.
AB  - Studies of ecological responses to climate change have often analysed species
      independently of each other, yet interactions between species are fundamental
      aspects of ecology. Mutshinda, O'Hara & Woiwod (2011) used light-trapping data
      for Lepidoptera (moths) to examine population responses to intraspecific effects
      and effects of winter rainfall and temperature. They show how Bayesian
      hierarchical models can analyse residual correlations among species' responses,
      illustrating an approach to account for and measure dependencies that are not
      fully explained by the candidate explanatory variables. A key result is that the
      responses of the different moth species did not appear to have strong residual
      correlation (Mutshinda, O'Hara & Woiwod 2011). These analyses provide an approach
      for synthesising across species and can better inform ecological responses to
      environmental change.

PMID- 21188840
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system. Dominant contributors for systemic
      hypertension--who leads, who follows?

PMID- 21188836
TI  - Rift Valley fever virus(Bunyaviridae: Phlebovirus): an update on pathogenesis,
      molecular epidemiology, vectors, diagnostics and prevention.
AB  - Rift Valley fever(RVF) virus is an arbovirus in the Bunyaviridae family that,
      from phylogenetic analysis, appears to have first emerged in the mid-19th century
      and was only identified at the beginning of the 1930's in the Rift Valley region
      of Kenya. Despite being an arbovirus with a relatively simple but temporally and
      geographically stable genome, this zoonotic virus has already demonstrated a real
      capacity for emerging in new territories, as exemplified by the outbreaks in
      Egypt (1977), Western Africa (1988) and the Arabian Peninsula (2000), or for re
      emerging after long periods of silence as observed very recently in Kenya and
      South Africa. The presence of competent vectors in countries previously free of
      RVF, the high viral titres in viraemic animals and the global changes in climate,
      travel and trade all contribute to make this virus a threat that must not be
      neglected as the consequences of RVF are dramatic, both for human and animal
      health. In this review, we present the latest advances in RVF virus research. In
      spite of this renewed interest, aspects of the epidemiology of RVF virus are
      still not fully understood and safe, effective vaccines are still not freely
      available for protecting humans and livestock against the dramatic consequences
      of this virus.

PMID- 21188841
TI  - Comments on Point:Counterpoint: The dominant contributor to systemic
      hypertension: Chronic activation of the sympathetic nervous system vs. Activation
      of the intrarenal renin-angiotensin system. Hung jury?

PMID- 21188842
TI  - Molecular models for mouse sperm-oocyte binding.
AB  - Binding of sperm to egg in the mouse has been proposed to depend primarily on
      interactions between lectin-like egg-binding proteins on the sperm plasma
      membrane and complementary carbohydrates on the specialized extracellular matrix
      of the egg known as the zona pellucida. An alternative model posits that initial
      sperm-egg binding depends on the interaction of a sperm surface protein with a
      supramolecular complex of the three mouse zona pellucida glycoproteins (mZP1,
      mZP2, mZP3); the role of carbohydrate recognition in this paradigm is thought to
      be minimal (Gahlay G, Gauthier L, Baibakov B, Epifano O,Dean J. 2010. Gamete
      recognition in mice depends on the cleavage status of an egg's zona pellucida
      protein. Science.329:216-219). This perspective reviews these recent findings,and
      considers them in light of evidence favoring a major role for lectin-like
      interactions. An alternative model, the domain specific model for mammalian
      gamete binding, could reconcile some of the conflicting observations.

PMID- 21188843
TI  - I know it's important to eat fish to benefit from the heart-healthy omega-3 fats
      it contains, but how can I incorporate more fish into my diet?

PMID- 21188844
TI  - Can diabetes affect brain function? Does it increase the risk of Alzheimer's
      disease?

PMID- 21188845
TI  - ZnO-based dye solar cell with pure ionic-liquid electrolyte and organic
      sensitizer: the relevance of the dye-oxide interaction in an ionic-liquid medium.
AB  - The use of non-volatile electrolytes and fully organic dyes are key issues in the
      development of stable dye-sensitized solar cells (DSCs). In this work we explore
      the performance of ZnO-based DSCs sensitized with an indoline derivative coded
      D149 in the presence of a pure ionic-liquid electrolyte. Commercial
      nanostructured zinc oxide and an electrolyte composed of iodine plus (1) pure 1
      propyl-3-methyl imidazolium iodide (PMII) and (2) a blend of PMII with low
      viscosity ionic liquids were employed to construct the devices. Without further
      additives, the fabricated devices exhibit remarkable short-circuit photocurrents
      and efficiencies under AM1.5 simulated sunlight (up to 10.6 mA cm-2, 2.9%
      efficiency, 1 sun, active area = 0.64 cm2) due to the high surface area of the
      ZnO film and the high absorptivity of the D149 dye. Impedance spectroscopy is
      used to characterize the devices. It is found that the addition of the low
      viscosity ionic-liquid improves the transport features (leading to a better
      photocurrent) but it does not alter the recombination rate. The robustness of the
      dye-oxide interaction is tested by applying continuous illumination with a Xenon
      lamp. It is observed that the photocurrent is reduced at a slow rate due to
      desorption of the D149 sensitizer in the presence of the ionic liquid.
      Exploration of alternative ionic-liquid compositions or modification of the ZnO
      surface is therefore required to make stable devices based on ZnO and fully
      organic dyes.

PMID- 21188846
TI  - In memoriam: Ellsworth C. Alvord, Jr (1923-2010).

PMID- 21188847
TI  - Novel and recurrent connexin 30.3 and connexin 31 mutations associated with
      erythrokeratoderma variabilis.
AB  - Erythrokeratoderma variabilis (EKV) is characterized by fixed hyperkeratotic
      plaques and transient erythema. Mutations in the genes GJB3 and GJB4, which
      encode connexin (Cx)31 and Cx30.3, are associated with EKV. We report one novel
      mutation in Cx31 and one recurrent mutation in Cx30.3 in two different families.
      One novel rare sequence variant of unknown clinical significance was also
      identified. This finding extends the spectrum of known EKV-associated mutations.

PMID- 21188848
TI  - Appropriate within-subjects statistical models for  the analysis of baroreflex
      sensitivity.
AB  - An individuals baroreflex sensitivity is typically described by the relationship
      between serial manipulations in systolic blood pressure and the changes in pulse
      interval. Although this experimental approach is essentially within-subjects in
      nature, least squares regression (LSR) analysis is typically employed by
      researchers to derive sensitivity slopes (gains) for individual subjects. These
      individual gains are then pooled as summary measures for various samples or
      experimental conditions. We highlight that the underlying assumption for LSR of
      case independence is violated with such an approach, resulting in possible
      estimation biases and compromised statistical power. Using a typical data set, we
      introduce more appropriate analyses based on the linear mixed model, which takes
      into account the correlated nature of the data at the individual subject level.
      We encourage researchers to consider the linear mixed model approach because it
      is more efficient, in that the whole data set is analysed in one step, is
      associated with less bias and results in greater statistical power compared with
      conventional analyses of baroreflex sensitivity for samples of subjects.

PMID- 21188849
TI  - Evaluation of the dose range of etoricoxib in an acute pain setting using the
      postoperative dental pain model.
AB  - OBJECTIVE: This study was conducted to evaluate the dose range of etoricoxib in
      acute pain using the postoperative dental pain model further. METHODS: This
      double-blind, randomized controlled study evaluated etoricoxib (90 and 120 mg),
      ibuprofen (600 mg), and acetaminophen (600 mg/codeine) (60 mg, (A/C)) in patients
      aged >= 18 years with moderate or severe pain after surgical extraction of >= 2
      third molars (>= 1 impacted). The patients reported pain intensity and pain
      relief over 24 hours. The primary efficacy endpoint was total pain relief over 6
      hours (TOPAR6). Adverse events were evaluated throughout the study. RESULTS:
      There were 588 patients randomized to placebo (n=46),etoricoxib (90 mg (n=191)),
      etoricoxib (120 mg (n=97)), ibuprofen(2400 mg (n=192)), and A/C (n=62). The
      overall analgesic effect (TOPAR6) of etoricoxib (90, 120 mg) was significantly
      greater than that of placebo (P <= 0.001), and not inferior to that of ibuprofen;
      no discernible difference was observed between etoricoxib 90 and 120 mg. Both
      etoricoxib doses were superior to A/C (P <= 0.001). Etoricoxib (90 and 120 mg)
      and ibuprofen(2400 mg) were generally well tolerated and had a similar incidence
      of adverse events (AEs). A/C was associated with significantly more AEs that led
      to discontinuation (ie, nausea and vomiting). CONCLUSIONS: Etoricoxib (90 and 120
      mg) showed similar efficacy in the postoperative dental pain model, which was
      noninferior to ibuprofen and superior to A/C. A higher number of tooth
      extractions or a higher mean impaction score may have led to a greater separation
      in efficacy between the 2 etoricoxib doses.

PMID- 21188851
TI  - Harm promotion: observations on the symbiosis between government and private
      industries in Australasia for the development of highly accessible gambling
      markets.
AB  - AIM: To illustrate ways in which industry control over the gambling market and
      its regulatory system have enabled rapid proliferation in gambling consumption
      and harm. METHOD: To discuss the relationship between government regulation and
      the accessibility, marketing and technologies of electronic gambling machines in
      Australia and New Zealand. FINDINGS: The regulatory framework for gambling in
      both countries has encouraged highly accessible,regressively distributed and
      heavily marketed high-impact electronic gambling machines. This framework has
      developed in large part through the conjunction of government revenue needs and
      the adaptation of a folk model of gambling appropriated by gambling businesses
      and engineered to incorporate a discourse that legitimate their gambling
      businesses. CONCLUSION: Governments should be encouraged to invest in 'upstream'
      public health strategies that contain the economic and social drivers for
      intensifying gambling consumption. One key aspect involves questioning the most
      suitable scale, location and marketing of gambling operations, and the reliance
      of government on gambling revenues (whether directly or as substitution for other
      government expenditure). Technological solutions to disrupt the development of
      obsessive gambling habits are also available and are likely to reduce gambling
      related harm.

PMID- 21188850
TI  - Chronic low back pain, sleep disturbance, and interleukin-6.
AB  - OBJECTIVES: Sleep disturbance is a common comorbidity of chronic pain.
      Inflammatory processes are dysregulated in sleep disturbance and also contribute
      to pain sensitivity. Thus, inflammation may play an important role in
      bidirectional associations between pain and sleep. Little is known about
      concurrent relationships among chronic pain, sleep, and inflammation. The aim of
      our study was to examine associations between sleep disturbance and circulating
      levels of the inflammatory cytokine, interleukin-6 (IL-6), in individuals with
      and without chronic low back pain. METHODS: Sex-matched and age-matched adults
      with chronic low back pain (CLBP; n=25) or without chronic pain (controls;
      n=25)completed measures of sleep quality in the past month and depressive
      symptoms in the past week, and provided a blood sample for IL-6. The next
      morning, participants reported their sleep quality the previous night and their
      current experience of morning pain. RESULTS: Individuals with CLBP had more sleep
      disturbance than controls. Circulating IL-6 levels were similar for the 2 groups;
      however, in adults with CLBP, poorer sleep quality was associated with higher IL
      6 levels, and both sleep and IL-6 related to pain reports. Unlike CLBP
      participants, controls showed normal, age-related increases in IL-6 levels,
      whereas sleep quality was unrelated to IL-6 levels. Depressive symptoms could not
      fully explain the observed associations. DISCUSSION: Inflammatory processes may
      play a significant role in the cycles of pain and sleep disturbance. Clinical
      interventions that improve sleep and reduce concomitant inflammatory
      dysregulation hold promise for chronic pain management.

PMID- 21188852
TI  - Regulating harm - gambling technology and the challenges for Great Britain.

PMID- 21188853
TI  - Harm minimization can be achieved by a symbiosis between government, industry and
      individuals.

PMID- 21188854
TI  - Before, during and after measures to reduce gambling harm.

PMID- 21188855
TI  - Commentary on Roettger et al. (2011): confronting the elephant in the room.

PMID- 21188856
TI  - Focus on doctor-patient relationship the secret to practice success.

PMID- 21188857
TI  - Transvaginal ultrasound imaging for assessment of early pregnancy.

PMID- 21188858
TI  - Counting and caring for chronically ill children: the need for a paediatric
      registry.

PMID- 21188859
TI  - [EBP/EBN, nursing education and update].
AB  - Evidence-based practice (EBM) has changed clinical practice because improved
      critical thinking, empowered the professionals public and allowed for the
      generalization of research findings to large populations. However, one of the
      central problems with EBM is when it is considered the only way to update
      knowledge and it is used as a cookbook approach and independent thought is
      sacrificed in the process.

PMID- 21188860
TI  - [Risk factors for one year hospitalization and death of 615 home care patients
      with multidimensional assessment].
AB  - INTRODUCTION: The District care activities are often presented as number of
      patients, interventions or home visits. A better description should render more
      visible the persons and their clinical problems whose outcomes should be
      monitored. AIM: To prospectically monitor the outcomes in a sample of home care
      patients followed for one year. METHODS: Six hundred sixty two home care patients
      of two Local Health Units of Veneto Region with at least two nurses visits per
      month had a multidimensional assessment and were followed for one year. RESULTS:
      At the end of follow-up 32% of patients had died, 3.9% had been admitted to a
      Nursing home; 41.9% had at least one hospital admission and for 49.7% the number
      of nursing visits was increased. Closeness to death and inadequate family support
      were independently associated to an increased risk of hospital admission, while
      patients with severe cognitive impairment tend to be admitted to hospital less
      frequently. Of the 216 bedridden patients those with inadequate family support
      are at higher risk for death and hospital admissions. CONCLUSIONS: Home care
      informative systems allow to assess and monitor the more severe patients thus
      producing information useful for the continuous improvement of caring processes.

PMID- 21188861
TI  - [How nurses update their knowledge: a survey in three north Italian hospitals].
AB  - INTRODUCTION: Evidence based nursing (EBN) implies the application of the best
      knowledge to clinical practice but nurses may rely on different sources of
      knowledge. AIMS: To gain knowledge on methods and sources nurses use to update
      their knowledge. METHODS: A self completed closed question questionnaire was
      administered to the nursing personnel of three north Italian hospitals. For each
      item a level of agreement (never (0) always, 5) was expressed. RESULTS: Over 2642
      questionnaires, 1549 (58.5%) were completed. Nurses mostly rely on their
      experience (mean 4), information obtained from protocols and guidelines (mean
      3.94) and during basic education (mean 3.82). Nurses that had attended courses of
      research or EBN read more frequently articles published in nursing or medical
      journals. CONCLUSIONS: Experience an important source of knowledge and education
      to research or EBN may impact on how nurses update their knowledge.

PMID- 21188862
TI  - [Nursing care during night shift: a narrative review of the literature].
AB  - INTRODUCTION: Although night duties cover more than 1/3 of the nursing care
      during hospitalizations, little attention is paid to activities performed and
      problems nurses encounter. METHODS: A literature review on Medline and Cinahl
      with the following key-words shift workers, nurses, night, nursing, assessment,
      night duty was performed to explore activities performed by nurses, and patients
      and nurses perceptions: 23 studies were included. RESULTS: Nurses perform planned
      and not planned activities. The most important function is patients
      vigilance/monitoring during night rounds. Although physically stressing, nurses
      recognize the value of night duties because they are fully responsible of the
      patients. Patients' main complaint is the noise that prevents sleep. CONCLUSIONS:
      Research is needed to study night duties and to set standards for an high quality
      of care during night shifts.

PMID- 21188863
TI  - [Reflective writing in nursing education: background, experiences and methods].
AB  - INTRODUCTION: In the nursing field, writing one's own educational/professional
      experience has been utilized for a long time, to develop reflection and therefore
      learning. Reflective writing has been fostered to sustain the development of
      nurses' clinical, relational and ethical competence, and to promote self
      knowledge. AIM: To de scribe reflective writing experiences published in the
      literature, focussing on the educational contexts and the writing strategies used
      in the nursing field. Method. Narrative analysis of the international literature,
      based on the MedLine and Cinahl data sources. RESULTS: Reflective writing is used
      in undergraduate, post-graduate and continuing nursing education, to develop
      clinical learning or a professional and/or personal growth. In the former, short
      written assignments (also starting from scenarios) are given, while diaries and
      journals, with prompts focalizing on specific aspects of the experience, support
      a more global growth of the student/professional. These prompts are useful with
      individuals not used to write. Critical incidents or meaningful episodes from the
      clinical practice are also used. Many papers underline the importance of sharing
      writings with peers and/or a teacher/facilitator. CONCLUSIONS: Nursing
      students/professionals can be effectively supported by reflective writing in
      their experiential learning. However, their attitude to reflective writing should
      be considered with care and a feedback by peers and/or a facilitator must be
      provided. Since giving feedback requires adequate human resources, the
      implementation of writing activities in the nursing training should be carefully
      evaluated.

PMID- 21188864
TI  - [Globalization and socio-economic inequalities].

PMID- 21188865
TI  - [The changes in the English National Health Service].
AB  - The recent wite paper "Equity and excellence: liberating the NHS" describes the
      future changes of the English NHS, promoting a radical liberalization of the NHS
      within a framework of public funding and guaranteeing equitable and safe care for
      all. The main messages and implications of this incoming reform are analyzed.

PMID- 21188866
TI  - [Palliative care for the terminal patient].

PMID- 21188867
TI  - [Dressings impregnated in antibacterial agent: multicenter study on acute and
      chronic wounds, with Atrauman Ag].
AB  - Ulcers and chronic wounds are an ideal medium for bacterial growth. This growth
      occurs in both number and variety of species, resulting in lesions with
      polymicrobial flora. The use of antimicrobial treatments to control and/or
      prevention of infection is discussed. Silver dressings as an alternative safe and
      effective for treating infected wounds and/or in situations of critical
      colonization. There are already evidence of what kind of silver-containing
      dressings are more cost-effective. The aim of this study is to evaluate the
      efficacy and effectiveness of Atrauman Ag dressing in the treatment of skin
      lesions in acute and chronic, as to the resolution of signs of infection and
      progression of healing during a period of four weeks. MATERIAL AND METHODS: we
      performed an observational, prospective, multicenter open study where the patient
      inclusion period was from April to August 2007. The sample consisted of patients
      seen giving their informed consent in primary care centers, health centers and
      hospitals throughout the country and met the inclusion criteria and had none of
      the exclusion criteria. The study variables were collected sociodemographic,
      injury-related variables to study with the dressing and the ratings of
      professionals and patients. The values of each variable were collected weekly in
      a CRD. The recorded data are processed in a database originally composed of 116
      variables, which were analyzed with SPSS software. RESULTS: we evaluated 219
      patients finally included 147 who met the inclusion criteria and no exclusion. At
      the end of the study had chronic injuries granulation tissue in 84.8% and 100%
      acute wounds with statistically significant differences with respect to the
      initial assessment. Exudate levels in wounds evaluated at 4 weeks of treatment
      show a significant reduction, from exudate abundant or very abundant in 81.8% to
      a level of low or moderate exudate in 80.5% of the cases end of the study The
      evolution of clinical signs of infection by 87% (n=91) of the lesions disappeared
      after 4 weeks. 11.7% of lesions were healed in the study period. In the case of
      chronic wounds, we go from a median of 17.5 cm2 to 9.9 cm2, this means a relative
      reduction of 39.05% and a speed of 1. 12 cm2/week healing. In the case of acute
      wounds, a move from a median of 8.25 cm2 to 3.0 cm2 and a relative reduction of
      65.03% with a healing rate of 2.28 cm2/week, with statistically significant
      differences both cases. The permeability of the dressing exudate was evaluated as
      good or very good in 88% of cases and the perilesional skin care by 79.9% as good
      or very good. The pain in the wounds was evaluated as nothing or very little, in
      72% of cases.

PMID- 21188868
TI  - [Telecare, one care vision].
AB  - Information and communication techniques represent a double challenge for
      nursery. This techniques provide the chance to improve the patient-sanitary
      professional relationship, promoting situations where the patient plays an active
      part in its own therapeutic process, and on the other hand arise the need to be
      ready for this technologic setting. The incorporation of the information and
      communication techniques will represent a new approach to the therapeutic
      relationship, that has to be used to consolidate the role of the nursery in front
      of the patient. Telecare offers services regarding health promotion, prevention
      and illness recovery based on information and communication techniques.

PMID- 21188869
TI  - [Accompany death].
AB  - One of the roles of nursing is to take care of the patients in terminal
      situation. The time, the experience, the formation, and the personal and
      professional attitudes that the nurse has will propitiate that taking care of
      moribund patients might turn into one of the more rewarding human experiences in
      life. There for, it is indispensable that nurses assume death as a natural and
      inevitable reality to achieve. The principal aim of the study is to evaluate the
      competence of confrontation and the autoefficiency of the welfare among nurses
      who work with adult patients at the end of the life. Descriptive study realized
      in the units of Oncology, Hametology and Palliative Care of the following
      centers: La Fe, Clinico, Dr. Peset, H. General, Arnau de Vilanova and Dr. Moliner
      de Portacoelli in Valencia (Spain). The following instruments were used: the
      Bugen Scale of confrontation of the Death (1980-1981) and the Robbins Scale of
      Autoefficiency (1992). Data suggests that major coping gives major autoeffciency
      and vice versa. The realized study opens numerous questions, specially related
      with training and the burden of preparation along the whole professional career,
      in order to achieve competence for coping and autoefficiency.

PMID- 21188870
TI  - [Chronic wounds treated with iodinated cadexomer. Study of a series of clinical
      cases with Iodosorb].
AB  - INTRODUCTION: presence of necrotic tissue in the wounds, high bacterial load and
      high levels of exudate have been identified as the main barriers to wound
      healing. Iodinated cadexomer, recently marketed in Spain, allows osmotic
      autolytic debridement, exudate management and infection control. This study aims
      to assess, in real clinical conditions and in an exploratory way the utility of
      iodinated cadexomer in the treatment of wounds with significant necrotic tissue.
      METHODS: observational descriptive study of a series of clinical cases with
      patients presenting chronic wounds with devitalized tissue and clinical signs of
      local infection, with wounds of any etiology and treated with iodinated cadexomer
      (Iodosorb). Patients were followed for 10 dressing changes or until healing if it
      was before 10 dressing changes. RESULTS: 70% of the lesions presented clean
      granulation tissue with 10 dressing changes. The management of infection and
      exudation also had good results. The clinical signs of infection disappeared
      after the fifth change of dressing, a fact which was entirely confirmed in the
      eighth. In relation to the management of exudate, more than 70% of the injuries
      were no longer infected in the second change of dressing and over 50% of the
      injuries had happened to have a slight or no exudate. Erythema and maceration of
      surrounding skin also showed significant improvement. An added value of the data
      is that six of the 21 lesions healed during the study and that pain was reduced
      sharply from a score of 6.5 to 3 on the second change of dressing and from zero
      to five, resulting in a substantial improvement in quality of life of these
      people. DISCUSSION AND CONCLUSIONS: this study suggests that iodinated cadexomer
      is useful for wound debridement, while reduces clinical signs of local infection
      and exudate levels normally associated with these situations.

PMID- 21188871
TI  - [For patients undergoing surgery, a reduction of risks and an increase in comfort
      by means using the Nobecutan aerosol].
AB  - This article summarizes the study which won the 2010 Nursing Nobecutan Prize,
      Second Edition. This study is an observational study of patients who undergo
      spinal column surgery. At the beginning of their surgical procedure, Nobecutan
      aerosol was applied to the affected area.

PMID- 21188872
TI  - [Educational innovation on the practices for the subjects of community nursing,
      mental health nursing and geriatric nursing].
AB  - The new European space for higher education requires changes in education manners
      as well as execution. One of the main challenges is for the students to acquire
      competence in their professional life. For that purpose they require knowledge,
      but also skills and a proactive attitude towards learning. In this paper we tell
      the experience of the Virgen de las Nieves School of Nursing in Granada, with
      regards to the integration of the practices for the subjects of Community Nursing
      III, Psychiatric and Mental Health Nursing, and Geriatric Nursing, which are
      taken in the third year of the Diplomatura en Enfermeria degree. Said practices,
      which were previously being offered separately within different contexts, will be
      merged in the same program whose scope will be Primary Care. We believe that the
      experience has been very positive by looking both at the results and the
      satisfaction of the students and the professional lecturers. It has been achieved
      an increase in the number of community care practice hours, and students have
      managed to acquire more autonomy in their learning and to incorporate critical
      reasoning in their education. In the methodology used, they have been the main
      evaluators and protagonists in their learning process, seeking the implication of
      professionals and teaching tutors in this change. The consensus on the objectives
      and methods, along with the obstacles which had to be overcome, constitutes one
      of the most interesting aspects of this experience.

PMID- 21188873
TI  - [Burns: nursing care].

PMID- 21188874
TI  - [New markers of acute kidney injury].
AB  - During the last few years, uniform criteria have been created for the diagnosis
      of acute renal insufficiency and its degree of severity. The term acute kidney
      injury covers all forms of acute damage regardless of the pathogenic mechanism.
      Acute kidney injury has been conventionally diagnosed on the basis of increased
      creatinine level or decreased urine volume resulting from impaired glomerular
      filtration. The detection of tubular injury enables an earlier diagnosis of acute
      kidney injury, because impairment of glomerular filtration often precedes the
      tubular injury. New markers are becoming available, which are more sensitive and
      more specific for kidney injury.

PMID- 21188875
TI  - [Kidney transplantation criteria in Finland].
AB  - In the treatment of end-stage renal disease, kidney transplantation is the best
      and most cost-effective alternative with regard to both prognosis and quality of
      life. Problems arise from the disproportion between the number of available
      allografts and the patients waiting for the transplantation. There are few
      absolute contraindications to kidney transplantation. In the assessment of the
      eligibility for transplantation of patients on dialysis the most important
      factors include cardiovascular diseases, cancer diseases, other diseases
      affecting operability and life expectancy, age, excess weight and possible
      infections.

PMID- 21188876
TI  - [The follow-up of kidney transplant patients].
AB  - Although the results of kidney transplantation have improved markedly, the long
      term survival of renal allografts is still a major challenge. The long-term
      exposure of recipients to chronic renal failure and chronic immunosuppression
      increases the burden of infections, cardiovascular diseases, malignancies, and
      renal bone disease. The prevention and adequate treatment of these complications
      have become increasingly important. During the first months after kidney
      transplantation patients are followed carefully with short intervals; in stable
      patients the follow-up frequency is reduced later. Most important laboratory
      tests in the follow-up include parameters of graft function and pharmacokinetic
      monitoring of the immunosuppressive drugs.

PMID- 21188877
TI  - [Seizures in newborn infant].
AB  - Seizures in newborn infants are common. The may constitute a neurologic emergency
      or a nonepileptic, harmless symptom. Diagnostics is becoming more specific with
      current methodologies. Detailed description of seizures and their connection with
      EEG abnormalities are the diagnostic cornerstones. The treatment has made slow
      progress, but newer antiepileptic drugs may aid in the treatment of epileptic
      seizures in newborn infants in the future. For the time being, evidence-based
      research results for them are lacking, as well as data on long-term effects.
      Differential diagnosis of seizures has become increasingly important.

PMID- 21188878
TI  - [Update on current care guidelines: obstructive sleep apnoea syndrome in adults].
AB  - Diagnosis of obstructive sleep apnoea syndrome (OSAS) is based on the patient
      history, clinical examination and sleep study. Untreated OSAS increases the risk
      of cardiovascular diseases, traffic accidents, lost work days and mortality.
      Weight loss forms the basis of treatment in obese patients. Continuous positive
      airway pressure (CPAP) therapy is the treatment of choice in moderate/severe
      cases of OSAS. In selected cases, oral appliances or surgical treatment are of
      benefit.

PMID- 21188879
TI  - [Psychologically traumatized patient on a general practitioner's consultation].
AB  - Psychologic first aid and active observation ("watchful waiting") provided by a
      general practitioner will usually suffice as therapy for acute stress reaction
      and disorder. Drug therapy should be considered only with caution. If trauma
      related symptoms become prolonged, developing into a post-traumatic stress
      disorder, the general practitioner can continue to carry the responsibility for
      the treatment and follow-up, even though the psychotherapeutic treatment would be
      provided elsewhere. The first-line treatment of post-traumatic stress disorder is
      trauma-oriented therapy in its various forms. Combining psychotherapy with
      antidepressant medication may be contemplated.

PMID- 21188880
TI  - [Psychosocial support after school shootings--what was learned from the Kauhajoki
      case].
AB  - On September 29, 2008 in Kauhajoki, a student killed ten persons and committed
      suicide. Many people in the region were subjected to an extensive sensation of
      threat and experienced mental effects of the tragedy. Aftercare of the tragedy
      has been coordinated by the Kauhajoki project. The project has aimed at ensuring
      that persons and communities traumatized by the event in their life and
      functioning will receive the required psychosocial support and appropriate
      treatment. The goal is to restore the mental balance and to maintain the ability
      to work and function.

PMID- 21188881
TI  - [Psychological well-being of the young of Jokela and Kauhajoki--how are the young
      doing today?].
AB  - For most pupils and students, the school shootings in Jokela and Kauhajoki were
      the most traumatic incident of their life. The young and young adults of both
      schools have been asked to participate in a follow-up study, in which the
      recovery, psychic symptoms and functional ability of those having experienced the
      shooting trauma will be studied over a two-year follow-up period. Approximately
      30 to 40 % exhibited psychic symptoms at four months after the incident. Approx.
      one fifth suffered from post-traumatic stress disorder. The proportion of persons
      having symptoms decreased during the one-year follow-up period.

PMID- 21188882
TI  - [Treatment of a child's psychological trauma].
AB  - The effect of traumatic experiences on a child's growth and development as well
      as on subsequent health is wide and far-reaching. The progress in brain research
      has complemented the clinical experience concerning the way the mind and the
      brain elaborate on traumatic experiences. When providing help for children,
      developmental factors must be always considered without forgetting that
      children's ability to cope with insurmountably difficult situations is strongly
      dependent on the coping of the parents and the family. Treatment of posttraumatic
      stress disorder is based on good child psychiatric clinical practices.

PMID- 21188883
TI  - Docs as managers: how they-and you-can make it work. Interview by Bill Santamour.

PMID- 21188884
TI  - [Contribution of the faculty of pharmacy of Santiago de Compostela to the
      development of the Spanish scientific research in the first third of the 20th
      century (1900-1936)].
AB  - The Faculty of Pharmacy of Santiago de Compostela was founded in 1857, but
      research activities did not start until the beginning of the 20th century. The
      new Spanish regulations promoting the experimentation at universities and the
      stages of professors and recently graduated students outside Spain contributed to
      generate a remarkable research group in a provincial university. The excessive
      university centralism at that time in Spain and the characteristics of the
      headquarters of the faculty -- a 16th century Renaissance palace -- hindered, in
      general, the research development. However, the scientific spirit of professors
      and students, and their work were imposed and they achieved an estimable status
      in pharmacy research in Galicia. The facilities were the staff's highest priority
      and it raised more than a protest. A remarkable investment in apparatuses and
      laboratory materials was carried out and researchers started to publish original
      research papers in local journals, such as the "Revista de farmacia," published
      by their own University. In the previous years to the Spanish Civil War (1936)
      the research status in drug development and the background of the staff and
      students were important, allowing them to join the military laboratory that
      Franco's army created at the faculty of pharmacy. The research work continued in
      a small scale and was specially focused on the production of "copy drugs" coping
      European specific drugs which were scarce at that time. The first third of the
      20th century was the germ of the great research prestige that the Faculty of
      Pharmacy of Santiago de Compostela enjoys at present.

PMID- 21188885
TI  - Bulletin board. Study suggests that following surgery, watchful waiting may be a
      safe option for girls with early-stage ovarian germ cell tumors.

PMID- 21188886
TI  - Between the town and the mountain: abortion and the politics of life in Edith
      Wharton's "Summer".
AB  - In the early twentieth century, American laws focused on women's reproductive
      capacities and were coalescing into the ethical and moral frameworks that subtend
      American reproductive politics today. Edith Wharton published her 1917 novel,
      Summer, at a time when anti-abortion sentiment was widespread in American
      culture. Through a reading of Summer, the article provides a theoretical and
      historical framework for understanding this new American obsession with the
      judicial regulation of women's reproductive options. In particular, I situate the
      novel's presentation of abortion within the tension between the carefully defined
      laws of North Dormer, the town in which the majority of the story takes place,
      and the lawlessness of the Mountain, a place that looms throughout the story as
      the protagonist's birthplace and a location of utmost abjection. The novel's
      profound insight is that power does not function unilaterally and individually
      but through and on the population. Furthermore, Wharton leaps ahead by
      recognizing that life is not simply that which lives but that which is recognized
      and embraced by the law. This realization, one that Wharton must have come to
      terms with through her painful work with World War I refugees, shapes Charity's
      character and her understanding not only of how reproduction is regulated but
      also of how living within this regulation and control generates the norm and
      offers the only possibility for a liveable and legible life.

PMID- 21188887
TI  - Social networks among Indigenous peoples in Mexico.
AB  - We examine the extent to which social networks among indigenous peoples in Mexico
      have a significant effect on a variety of human capital investment and economic
      activities, such as school attendance and work among teenage boys and girls, and
      migration, welfare participation, employment status, occupation, and sector of
      employment among adult males and females. Using data from the 10 percent
      population sample of the 2000 Population and Housing Census of Mexico and the
      empirical strategy that Bertrand, Luttmer, and Mullainathan (2000) propose, which
      allows us to take into account the role of municipality and language group fixed
      effects, we confirm empirically that social network effects play an important
      role in the economic decisions of indigenous people, especially in rural areas.
      Our analysis also provides evidence that better access to basic services such as
      water and electricity increases the size and strength of network effects in rural
      areas.

PMID- 21188888
TI  - Domestic relations in Brazil: legacies and horizons.
AB  - Grounded in literature review and an ethnographic study, this article examines
      contemporary Brazilian domestic life. Relations among women (employers and maids)
      and between women and men are analyzed with a focus on the home as a space in
      which gender, race, and class inequalities are constantly reproduced. The article
      argues that what happens in domestic life is constitutive of wider social
      divisions and that the domestic is a universe integral to the national social
      context. A case in point is the connection between the widespread use of paid
      domestic labor and the naturalization of black women as subservient,
      complementing the pairing of whiteness and class entitlement. Another case is the
      buffering role of maids in the development of gender conflicts in well-off homes,
      thus blurring gender hierarchies at a broader scale. Locating the domestic within
      the recent discussion on global domestic labor, the article compares
      particularities of Brazilian domestic life to those elsewhere.

PMID- 21188889
TI  - The color of child mortality in Brazil, 1950-2000: social progress and persistent
      racial inequality.
AB  - Now that racism has been officially recognized in Brazil, and some universities
      have adopted affirmative-action admission policies, measures of the magnitude of
      racial inequality and analyses that identify the factors associated with changes
      in racial disparities over time assume particular relevance to the conduct of
      public debate. This study uses census data from 1950 to 2000 to estimate the
      probability of death in the early years of life, a robust indicator of the
      standard of living among the white and Afro-Brazilian populations. Associated
      estimates of the average number of years of life expectancy at birth show that
      the 6.6-year advantage that the white population enjoyed in the 1950s remained
      virtually unchanged throughout the second half of the twentieth century, despite
      the significant improvements that accrued to both racial groups. The application
      of multivariate techniques to samples selected from the 1960, 1980, and 2000
      census enumerations further shows that, controlling for key determinants of child
      survival, the white mortality advantage persisted and even increased somewhat in
      2000. The article discusses evidence of continued racial inequality during an era
      of deep transformation in social structure, with reference to the challenges of
      skin color classification in a multiracial society and the evolution of debates
      about color, class, and discrimination in Brazil.

PMID- 21188890
TI  - Reconstructing Indigenous ethnicities: the Arapium and Jaraqui peoples of the
      lower Amazon, Brazil.
AB  - In Latin America, indigenous identity claims among people not previously
      recognized as such by the state have become a key topic of anthropological and
      sociological research. Scholars have analyzed the motivations and political
      implications of this trend and the impacts of indigenous population's growth on
      national demographic indicators. However, little is known about how people
      claiming indigenous status constructs the meaning of their indigenous ethnicity.
      Drawing from sixty-four indepth interviews, focus-group analyses, and participant
      observation, this article explores the double process of identity construction:
      the reconstruction of the Arapium indigenous identity and the creation of the
      Jaraqui indigenous identity in Brazil's Lower Amazon. The findings reveal six
      themes that contribute to the embodiment of a definition of indigenous identity
      and the establishment of a discursive basis to claim recognition: sense of
      rootedness, historical memory, historical transformation, consciousness, social
      exclusion, and identity politics.

PMID- 21188891
TI  - Precursors to femicide: Guatemalan women in a vortex of violence.
AB  - Today women in Guatemala are killed at nearly the same rate as they were in the
      early 1980s when the civil war became genocidal. Yet the current femicide
      epidemic is less an aberration than a reflection of the way violence against
      women has become normalized in Guatemala. Used to re-inscribe patriarchy and
      sustain both dictatorships and democracies, gender-based violence morphed into
      femicide when peacetime governments became too weak to control extralegal and
      paramilitary powers. The naturalization of gender-based violence over the course
      of the twentieth century maintained and promoted the systemic impunity that
      undergirds femicide today. By accounting for the gendered and historical
      dimensions of the cultural practices of violence and impunity, we offer a re
      conceptualization of the social relations that perpetuate femicide as an
      expression of post-war violence.

PMID- 21188892
TI  - Household shocks, child labor, and child schooling: evidence from Guatemala.
AB  - Using data from the National Survey of Standards of Living conducted in Guatemala
      in 2000, this article tests the hypothesis that Guatemalan households use child
      labor and reduce child schooling to cope with household shocks. First, the
      authors use factor analysis to estimate the latent household propensity to
      natural disasters and socioeconomic shocks. Then, they estimate bivariate probit
      models to identify the determinants of child labor and schooling, including
      household propensity to natural disasters and socioeconomic shocks. Results
      suggest that households use child labor to cope with natural disasters and
      socioeconomic shocks. In contrast, the authors found no evidence that suggests
      that households reduce child schooling to cope with shocks. Findings also
      indicate that poor households are more likely to use child labor and schooling
      reduction as strategies to cope with socioeconomic shocks.

PMID- 21188893
TI  - Modernist re-orientations: imagining homoerotic desire in the "nearly" Middle
      East.

PMID- 21188894
TI  - Strike a pose. New data show the way you sit or stand can make you feel more
      powerful, with the testosterone to prove it.

PMID- 21188895
TI  - Pint-size me. San Francisco is talking toys out of Happy Meals. Will it make kids
      any healthier?

PMID- 21188896
TI  - The hidden advantages of quiet bosses.

PMID- 21188897
TI  - I can make your brain look like mine.

PMID- 21188898
TI  - Work pray love.

PMID- 21188899
TI  - What's the hard return on employee wellness programs?
AB  - Employee wellness programs have often been viewed as a nice extra, not a
      strategic imperative. But the data demonstrate otherwise, according to Berry, of
      Texas A&M University; Mirabito, of Baylor University; and Baun, of the University
      of Texas MD Anderson Cancer Center. Their research shows that the ROI on
      comprehensive, well-run employee wellness programs is impressive, sometimes as
      high as six to one. To achieve those kinds of results, employers cannot merely
      offer workers afew passes to a fitness center and nutrition information in the
      cafeteria. The most successful wellness programs are supported by six essential
      pillars: engaged leadership at multiple levels; strategic alignment with the
      company's identity and aspirations; a design that is broad in scope and high in
      relevance and quality; broad accessibility; internal and external partnerships;
      and effective communications. Companies in a variety of industries--including
      Johnson & Johnson, Lowe's, H-E-B, and Healthwise--have built their employee
      wellness programs on all six pillars and have reaped big rewards in the form of
      lower costs, greater productivity, and higher morale. Those benefits are not easy
      to achieve, and verifiable paybacks are never a certainty. But the track record
      inspires emulation, especially when you see the numbers.

PMID- 21188900
TI  - What brain science tells us about how to excel.
AB  - Millions of people are struggling at work. Some are in the wrong jobs. Others
      feel no connection to their colleagues or engagement with their. The result is
      rampant dissatisfaction and underachievement. Hallowell, a child psychiatrist
      specializing in learning differences, describes the Cycle of Excellence, a plan
      for helping people achieve peak performance. It consists of five steps: Select a
      job that reflects what you like to do and what you do best and that adds value to
      the organization. Research has shown that good job fit reduces stress and
      increases satisfaction and performance. Connect with the people around you.
      Robust relationships in the workplace galvanize people and build their engagement
      with their jobs. Small talk may seem trivial, but it pays big dividends. Play on
      the job. It sounds like an oxymoron, but people do their best--and are most
      satisfied--when they're imaginatively involved with their work. And when you're
      hard at play, you're building your brain. Grapple and Grow--that is, work hard to
      achieve a difficult task. The stress you may feel as you engage with a tough
      assignment and connect with others to complete it is not the toxic kind. Shine in
      the acknowledgment of your achievements. Praise releases chemicals that make us
      feel good, and it fills our uniquely human need to be of value, to matter. If you
      aren't getting it, ask for it. The need for recognition is fundamental to optimal
      human performance.

PMID- 21188901
TI  - Improving your financial fortune.

PMID- 21188902
TI  - Finding the right retirement plan opportunities.

PMID- 21188903
TI  - Can your practice benefit from SEMI?

PMID- 21188904
TI  - Will you have enough?

PMID- 21188905
TI  - Long-term care insurance. Is it right for you?

PMID- 21188906
TI  - How much cash do you need?

PMID- 21188907
TI  - Transitioning to retirement.

PMID- 21188908
TI  - Proper consent forms can be good evidence.

PMID- 21188909
TI  - Let them paddle their own canoes. Discovering the fine line between helping and
      enabling.

PMID- 21188910
TI  - Legal. Get ahead in the transfer game.

PMID- 21188911
TI  - The twenty-fifth anniversary of Nursing Praxis in New Zealand.

PMID- 21188912
TI  - Cultural safety: does the theory work in practice for culturally and
      linguistically diverse groups?
AB  - Culturally diverse refugee and migrant groups under-utilise health services in
      New Zealand and cultural barriers are cited as reasons for not using health
      services. According to the Nursing Council nurses are required to demonstrate
      competency in culturally safe practice, yet cultural safety is determined by the
      person receiving the care. This article critically examines the theoretical base
      of the cultural safety guidelines for nursing practice with respect to culturally
      and linguistically diverse (CALD) groups. Two key questions were posed: have the
      guidelines led to culturally safe nursing practice in health care for CALD
      groups, and have the guidelines contributed to provision of culturally acceptable
      health care for CALD groups? It is concluded that further theoretical
      consideration should be given to the conceptual basis for including CALD groups
      in the cultural safety model. The cultural competencies required for culturally
      safe nursing practice need to apply to the care of all culturally diverse groups
      present in New Zealand. Recommendations are made for strengthening the cultural
      safety model, and the registered nurse competencies for culturally safe practise.

PMID- 21188913
TI  - Staff beliefs about sexuality in aged residential care.
AB  - Expression of sexuality is a lifelong need and a basic human right, yet little is
      known about how staff in aged care facilities approach and manage the sexuality
      needs of residents. Fifty-two staff members from the rest home component of aged
      care facilities in one District Health Board completed a survey anonymously.
      Findings indicated that while the majority believe residents have sexual needs
      that should be acknowledged and supported, expression of sexuality often created
      discomfort and the need was not regularly assessed, or managed by a team
      approach. Lack of privacy, negative staff and family attitudes plus the
      difficulty of managing risk make responding to sexuality a complex issue. The
      combination of individual and institutional barriers suggest that thoughtful and
      creative team strategies are required to address the sexuality related needs of
      the older person in residential care.

PMID- 21188914
TI  - NGA Tukitanga Mai Koka Ki Tona Ira: Maori mothers and child to mother violence.
AB  - In common with other indigenous women Maori mothers risk illness, harm, and
      possible death when abused and intimidated by their children. Yet women suffering
      child to mother violence are silenced by their fear and shame, and endeavour to
      minimise the effects of this form of abuse. A qualitative descriptive research
      design using kaupapa Maori methodology was adopted to explore the experiences of
      Maori mothers who had been abused by a son or daughter. During semi-structured
      interviews with five Maori women experiences of abuse by a child, and its impact
      on the whanau/family were recorded. Interview transcripts were analysed
      thematically, and three key themes emerged: behind closed doors, my child and a
      new journey. These Mari mothers carried the secret of the violence alone; keeping
      it behind closed doors while paradoxically protecting their abusive child.
      Nonetheless, these mothers reached a point where they chose to undertake a new
      journey, one that involved telling their story, reconnecting with their
      indigenous roots, and engaging in healing activities. The mothers' experiences
      highlight a lack of support and responsiveness by support and health agencies.
      Regardless of these negative experiences with support agencies, we highlight the
      important role nurses have in facilitating whanau ora (family wellbeing) for
      these women. This research contributes an indigenous perspective to the growing
      literature on child to mother violence, and provides direction for future
      research.

PMID- 21188915
TI  - Major public health problems in developing countries.

PMID- 21188916
TI  - Caries experience and oral hygiene status of cerebral palsy children in Riyadh.
AB  - The purpose of this study was to determine the caries experience and oral hygiene
      (OH) status of cerebral palsy (CP) children in Riyadh area. One hundred and forty
      CP children [82 (58.6%) males & 58 (41.4%) females] were examined for dental
      caries and OH status in dental clinic of the Disabled Children's Association
      Center, Riyadh. The children were divided into three age groups; first group 3-6
      years old (41 children), second group 7-9 years old (52 children) and third group
      10-12 years old (47 children). The mean DMFS (decayed, missing and filled
      surfaces) score for the first group was 18.8 (+/- 16.3), with the DS component of
      10.9 (+/- 7.5), MS component of 3.7 (+/- 10.4) and FS component of 4.1 (+/- 8.9).
      For the second group the mean DMFS was 23.4 (+/- 17.7) with DS component of 15.4
      (+/-12.1), MS component of 4.1 (+/-9.0) and FS component of 3.8 (+/- 8.5). The
      corresponding values for the third group were 20.5 (+/- 14.0), 12.4 (+/- 9.7),
      5.1 (+/- 12.4) and 2.9 (+/- 5.5) respectively. There was no statistically
      significant difference (p > 0.05) in caries experience between the three age
      groups. Very few (5.7%) CP children were rated as having good OH. There was a
      strong association between poor oral hygiene status and high DMFS score. It can
      be concluded that the caries experience of CP children in Riyadh is very high,
      and that very few of these children have good oral hygiene.

PMID- 21188917
TI  - Fluoride contents of some Nigerian dentifrices.
AB  - OBJECTIVES: To analyze the fluoride content of different brands of toothpastes
      and powders commercially available in Nigerian markets, to compare the claims of
      the manufacturers with the objectively obtained results of the analysis and to
      make recommendations to the Regulatory Agencies based on the results of analysis.
      METHOD: Standard Operating Procedures (SOP) were used to measure the
      concentration of fluoride in randomly selected samples using fluoride ion
      selective electrode. RESULTS: Of the twelve samples analyzed, two toothpastes
      were purchased at Newcastle. Ten samples (eight toothpastes and two powders) were
      brought over from Nigeria. Three of the twelve were found to be deficient in the
      quantity of fluoride contained. All the deficient three samples found wanting
      were from Nigeria--a thirty per cent (30%) of the Nigerian samples. CONCLUSION:
      The importance of fluoride in caries prevention has been well documented and
      appreciated as public health measure. All efforts geared towards making fluoride
      available to the public especially through the dentifrices should be encouraged
      and guarded against mercantilism and abuse. To this end, the Nigerian Dental
      Association and the National Agency for Food and Drug Administration and Control
      (NAFDAC) should increase their surveillance over the quality of the products
      marketed.

PMID- 21188918
TI  - The sensitivity, specificity and accuracy of fine needle aspirational cytology in
      the diagnosis of oro-facial neoplasms at Lagos University Teaching Hospital,
      Nigeria.
AB  - OBJECTIVE: The aim of the study is to compare the efficacy of fine needle
      aspirational cytology (FNAC) with open surgical biopsy in the diagnosis of
      orofacial tumours in patients seen at the Dental Centre of Lagos University
      Teaching Hospital from May 2005-May 2006. PATIENTS AND METHODS: Fine needle
      aspiration was performed on all patients scheduled for open surgical biopsy at
      the Oral and Maxillofacial clinic of the hospital before the open surgical biopsy
      was done. Forty six patients whose final histological diagnoses were oro-facial
      neoplasms were involved in this study. Sensitivity, specificity and accuracy for
      fine needle aspirational cytology were calculated. RESULTS: The sensitivity,
      specificity and accuracy of fine needle aspirational cytology in the diagnosis of
      oro-facial tumours were 95%, 95.8% and 95.5%, respectively. The false positive
      and false negative rates were 5% and 4.2%, respectively. CONCLUSION: The high
      sensitivity, specificity and accuracy of fine needle aspirational cytology
      reported in this preliminary study suggest that the test may have a place in the
      management of oro-facial tumours. However, when the result of fine needle
      aspirational cytology is not in agreement with the clinical diagnosis, especially
      in suspected malignancy, open surgical biopsy should be performed.

PMID- 21188919
TI  - Do active ingredients in non alcoholic chlorhexidine mouth wash provide added
      effectiveness? Observations from a randomized controlled trial.
AB  - BACKGROUND AND OBJECTIVE: Chlorhexidine (CHX) is the most tested and leading oral
      antiseptic agent. Zinc as an active ingredient has shown additive and synergistic
      effect and when Sodium fluoride (NaF) was used it failed to show added
      effectiveness and the combined effect of NaF and Zinc chloride (ZnCl2) both as
      active ingredients has never been evaluated. The present study assessed the
      effectiveness of active ingredients and to compare the frequency of adverse
      events occurring with traditional CHX and CHX+NaF+ZnCl2. MATERIAL AND METHODS: A
      randomized double blind crossover trial was executed with 24 subjects
      participating in two consecutive experimental phases of 21 days each with CHX and
      CHX+NaF+ZnCl2 mouth rinses. Each individual was assessed for gingivitis, plaque,
      supragingival calculus and extrinsic stains at baseline and after experimental
      phase and adverse events experienced were recorded. RESULTS: There was a
      significant difference (p = 0.014) between the two experimental mouth rinses for
      their effectiveness on gingivitis. In the CHX group, the gingival score on D21
      was significantly greater by 0.13 than DO while with CHX+NaF+ZnCl2 there was a
      decrease in gingival score by 0.09 which was insignificant. No significant
      difference was observed between the interventions for plaque accumulation and
      formation of extrinsic stains. The difference in the mean calculus score at
      baseline and after experimental phase was 1.47 for CHX+NaF+ZnCl2 in contrast to
      1.93 among CHX group. Oral itching, oral soreness, apthous ulcers and dryness
      were reported by many subjects while burning sensation was reported by very few
      volunteers. There was no significant difference for occurrence of adverse events
      between the two experimental mouthrinses. CONCLUSIONS: CHX+NaF+ZnCl2 mouth rinse
      was found to be significantly more effective in the reduction of gingivitis and
      supragingival calculus. No significant difference was found for the occurrence of
      dental plaque, extrinsic stains and adverse events between the interventions.

PMID- 21188920
TI  - A review of orthodontic bond failure using a chemical cure adhesive.
AB  - INTRODUCTION: Orthodontic treatment involves the direct bonding of brackets to
      the tooth surface. These bonds should survive until the end of active treatment.
      The objective of this study was to clinically determine the frequency and bond
      failure pattern at the orthodontic clinic in the Lagos University Teaching
      Hospital, (LUTH) within a two-year period. MATERIALS AND METHODS: A total of 1926
      stainless steel Roth .022 brackets (Ultraminitrim Dentaurum, Germany) in 113
      patients were bonded using Rely-a-bond No-mix Adhesive (Reliance Orthodontic
      Products Inc., U.S.A.) over a two-year period. The effects of age, gender, arch
      location and position of the tooth in the arch on failure rate were evaluated.
      The mean time to first bond failure was also determined. RESULTS: A failure rate
      of 24.1% was recorded. The mean age at onset of treatment was 18.08 years. There
      was female preponderance with a male to female ratio of 1:3. The failure rate in
      males was 26.2% and in females 23.4%. The failure rates among the different age
      groups are as follows; 6-11 years 30.7%, 12-17 years 36.2%, 18-25 years 10.2%, 26
      and above years 9.1%. The failure rate was significantly higher in the mandibular
      teeth and teeth in the posterior location of the arch. CONCLUSION: Out of 1926
      bonded brackets there was a failure rate of 24.1% with a higher rate of failure
      in the younger age group, mandibular teeth and teeth in the posterior location of
      the arch.

PMID- 21188921
TI  - The ever-expanding workweek.

PMID- 21188922
TI  - 7 tips to increase your professional happiness productivity.

PMID- 21188923
TI  - Seeing patients as 'gold nuggets in a muddy stream'.

PMID- 21188924
TI  - Family affair.

PMID- 21188925
TI  - Protecting your practice.

PMID- 21188926
TI  - A deeper level of healing.

PMID- 21188927
TI  - Take these steps if selling or closing a practice.

PMID- 21188928
TI  - Some patients change our outlook.

PMID- 21188929
TI  - Nurses urged to prepare for outcome indicators.

PMID- 21188930
TI  - Staff shortages force closure of emergency department.

PMID- 21188931
TI  - European exchange scheme set up for nurses to share best practice.

PMID- 21188932
TI  - Time to retire?

PMID- 21188933
TI  - Mentoring in emergency care: 'growing our own'.
AB  - Historical attitudes to graduates in emergency departments (EDs) and the effect
      of nursing staff shortages conspire to make EDs demanding areas in which to begin
      a nursing career. New graduates can become competent and efficient nurses more
      easily, however, if they are guided by mentors. This article examines mentoring
      from a formal and informal perspective, and includes the author's personal
      reflection on her experiences of being mentored in an ED in Canada.

PMID- 21188934
TI  - Diagnosis and treatment of meralgia paresthetica.
AB  - Many patients present to emergency departments with lower back pain, for which
      there are several differential diagnoses. One of these is meralgia paresthetica,
      an obscure and benign condition first described in the late 19th century. Nurse
      practitioners should familiarise themselves with the symptoms of meralgia
      paresthetica so that they can make differential diagnoses and offer the relevant
      management. This article describes the condition, its causes and some
      conservative management techniques.

PMID- 21188935
TI  - Management of minor head injury in adults.
AB  - Head injury accounts for up to 20 per cent of emergency department (ED)
      attendances (Kay and Teasdale 2001), and approximately 800,000 patients attend
      U.K. EDs with head injuries every year (National Institute for Health and
      Clinical Excellence (NICE) 2007a, Scottish Intercollegiate Guidelines Network
      (SIGN) 2009). About 90 per cent of these patients have a mild or minor head
      injury and are managed in EDs before being discharged home (Swann and Teasdale
      1999). NICE in England and Wales and SIGN in Scotland have issued guidelines for
      the early management of head injury in adults in an attempt to improve clinical
      practice. This article discusses the important role of emergency nurses,
      particularly with regard to discharge information and advice for patients,
      relatives and carers.

PMID- 21188936
TI  - Care after chemical, biological, radiation or nuclear events.
AB  - Prompt airway management after chemical, biological, radiation or nuclear (CBRN)
      incidents is crucial for patient survival. To date, however, the ideal airway
      device for use by healthcare professionals wearing CBRN-personal protective
      equipment has not been ascertained. This article discusses findings from a review
      of clinicians' experiences of using six intermediate airway devices for use while
      wearing personal protective equipment

PMID- 21188937
TI  - Criminalizing HIV transmission or exposure: the context of francophone West and
      Central Africa.
AB  - Nations throughout the world are increasingly criminalizing HIV transmission or
      exposure. This trend, already very familiar to high-income countries such as
      Canada, the United States of America and some European nations, takes on a
      special meaning in Africa, where several national HIV/AIDS laws make HIV
      transmission or exposure a crime.

PMID- 21188939
TI  - British Columbia project seeks to improve access to HIV treatment and care among
      hard-to-reach populations.
AB  - A four-year, $48 million pilot program called "Seek and Treat" was recently
      launched by the government of British Columbia to improve access to treatment and
      care among hard-to-reach communities, including sex workers, injecting drug users
      and aboriginal people. The project will operate in Prince George and in
      Vancouver's Downtown Eastside.

PMID- 21188938
TI  - MSM law in francophone Africa and the fight against AIDS: the hypocrisy of
      certain countries.
AB  - In addition to being the targets of frequent discrimination and violence,African
      men who have sex with men (MSM) are being hit hard by the HIV/AIDS epidemic.
      Although there is still insufficient research regarding the methods of HIV
      transmission in sub-Saharan Africa, several studies show that the prevalence of
      HIV infection among MSM is more than ten times higher than among the general
      population.

PMID- 21188940
TI  - Multi-million dollar AIDS vaccine project cancelled.
AB  - Two years after calling for applications, the Government of Canada and the Bill &
      Melinda Gates Foundation decided not to proceed with a planned $88 million
      project to build an HIV vaccine plant, raising questions about what was behind
      the move.

PMID- 21188941
TI  - Surveys in Quebec reveal workplace discrimination against people living with
      HIV/AIDS.
AB  - Two recent surveys reveal that people living with HIV/AIDS (PLWHIV) continue to
      suffer discrimination in the workplace from both colleagues and employers.
      Findings from the surveys, which were commissioned by the Coalition des
      organismes communautaires Quebecois de lutte contre le sida (COCQ-SIDA), were
      released in November 2009.

PMID- 21188942
TI  - Historic trauma contributes to high rates of hepatitis C among Aboriginal youth:
      study.
AB  - A recent study conducted of Aboriginal youth in British Columbia suggests that
      trauma associated with the residential schools system increases the risk of
      hepatitis C virus (HCV) infection among those who inject drugs. The study also
      warns of a larger epidemic of HCV in the northern area of the province.

PMID- 21188943
TI  - Kenyan government to establish special tribunal for HIV-related issues.
AB  - On 21 January 2010, Kenyan government officials formally announced the creation
      of the first-ever tribunal dedicated to hearing legal issues related to HIV/AIDS.
      Among other things, the Tribunal will handle issues relating to the transmission
      of HIV; confidentiality of medical information and records; testing; access to
      healthcare services; discriminatory acts and policies; and HIV-related research.

PMID- 21188944
TI  - South Africa: new policy means more opportunities for HIV-positive soldiers.
AB  - In late 2009, the South African government announced that it had approved a new
      HIV/AIDS policy for the South African National Defence Force (SANDF). The move
      means that HIV-positive soldiers will be allowed to serve in foreign deployments
      and be promoted.

PMID- 21188945
TI  - B.C. Court of Appeal upholds supervised injection site's right to operate.
AB  - On 15 January 2010, the British Columbia Court of Appeal held that Insite, North
      America's first supervised injection site, was a provincial undertaking that did
      not undermine the federal goals of protecting health or eliminating the market
      that drives drug-related offences. As such, the Court held, the drug possession
      and trafficking provisions of the Controlled Drugs and Substances Act (CDSA) did
      not apply to it.

PMID- 21188946
TI  - Ontario court justice dismisses class action suit of persons notified of exposure
      to tuberculosis.
AB  - A recent decision of the Ontario Superior Court of Justice to dismiss a class
      action suit by individuals who had been notified of possible exposure to
      tuberculosis and who later required testing has important implications for the
      public health practice of mounting public notification campaigns to encourage
      testing to reduce the spread of communicable diseases such as tuberculosis (TB)
      and HIV.

PMID- 21188947
TI  - Coroner's jury recommends improved care for HIV-positive prisoners.
AB  - Following an inquest into the 2007 death of a young man in his twenties who had
      died from AIDS-related causes while serving a sentence in an Ontario correctional
      facility, a jury issued a number of recommendations to improve the treatment and
      care of HIV-positive individuals in prison.

PMID- 21188948
TI  - Ontario court strikes civil suit against Toronto and Ontario for failing to
      protect plaintiff from contracting HIV.
AB  - On 10 March 2010, the Ontario Superior Court of Justice struck in its entirety
      Percy Whiteman's statement of claim against Ontario and Toronto for negligently
      failing to protect him from contracting HIV from his spouse, holding that it
      disclosed no reasonable cause of action. Whiteman's claim that Canada was
      vicariously liable for the acts of immigration agents and employees was allowed
      to proceed, as it was not plain and obvious that no private law duty of care
      could be found to exist between Whiteman and Canada.

PMID- 21188949
TI  - HIV-positive Zimbabwean couple's refugee claim accepted on the basis of their
      political affiliation.
AB  - On 23 November 2009, the Refugee Protection Division of the Immigration and
      Refugee Board (IRB) found two citizens of Zimbabwe to be Convention refugees
      based on their political affiliation with Zimbabwe's opposition party and the
      impact this had on their access to antiretroviral treatment in Zimbabwe. The
      refugee claims of their children, who were not infected with the virus, were
      rejected.

PMID- 21188950
TI  - Federal Court dismisses appeal in permanent residence case, says personal
      commitments to pay for HIV treatment are unenforceable.
AB  - On 16 February 2010, the Federal Court dismissed the judicial review application
      of Al-Karim Ebrahim Rashid on the basis that personal commitments to pay for
      required health services such as HIV treatment are non-enforceable.

PMID- 21188951
TI  - Federal Court orders review of prospective immigrants' plan to obtain private
      insurance for HIV medication.
AB  - On 31 December 2009, the Federal Court allowed the judicial review application of
      Ricardo Companioni and his common-law partner on the basis that the ability and
      willingness of the applicants to defray the cost of their out-patient
      prescription drug medications is a relevant consideration in assessing whether
      the demands presented by an applicant's health condition constitute an "excessive
      demand".

PMID- 21188952
TI  - Criminal law and cases of HIV transmission or exposure.

PMID- 21188953
TI  - South Africa: ANC Youth League President found guilty of hate speech.
AB  - On 15 March 2010, the Johannesburg Equality Court found African National Congress
      (ANC) Youth League President Julius Malema guilty of hate speech and harassment
      for his comments regarding rape survivors.

PMID- 21188954
TI  - High Court in India decides property dispute in favour of HIV-positive widow.
AB  - On December 22, 2009 the Calcutta High Court settled a property dispute in favour
      of an HIV-positive widow. This decision has been described as setting "a new
      bench mark," both because of the outcome of the case and the speed with which a
      settlement was achieved.

PMID- 21188955
TI  - HIV-positive worker in Ecuador takes his employer to court for discrimination.
AB  - The Ecuadorian Constitutional Court is currently considering the case of a person
      living with HIV/AIDS who claims that, contrary to federal and international laws,
      he was dismissed from his employment in the fall of 2009 because of his HIV
      status.

PMID- 21188956
TI  - Criminal law and cases of HIV transmission or exposure.

PMID- 21188957
TI  - Synergistic effects of ultraviolet A/riboflavin and glucose on corneal collagen
      cross-linking.
AB  - PURPOSE: To investigate the possible synergistic effect of ultraviolet A
      (UVA)/riboflavin and glucose on corneal collagen cross-linking (CXL) by means of
      the mechanical properties and thermal shrinkage temperatures. METHODS: Forty
      rabbits were divided into four groups: control group; UVA/glucose group;
      UVA/riboflavin group; and UVA/riboflavin/glucose group. After the treatments, the
      mechanical properties and thermal shrinkage temperatures of the corneal strips
      were analyzed to determine the CXL effects of corneal collagen induced by
      different treatments. RESULTS: Compared with the control group and other
      experimental groups, the UVA/riboflavin/glucose group showed significant
      alterations of the biomechanical properties. The ultimate stress value for the
      UVA/riboflavin/glucose group was increased by 120%, ultimate strain decreased by
      80%, and Young's modulus increased by 70% relative to the control group. An
      increase in ultimate stress by 24.5%, a decrease in ultimate strain by 34%, and
      an increase in Young's modulus by 17.4% were found in the UVA/riboflavin/glucose
      group compared to the UVA/riboflavin group. A significant increase in thermal
      shrinkage temperatures was also noted after corneal collagen CXL induced by
      UVA/riboflavin/glucose relative to other groups. CONCLUSIONS: The combination of
      glucose and UVA/riboflavin may synergistically induce corneal collagen CXL,
      resulting in increased mechanical strength of corneal collagen.

PMID- 21188958
TI  - Intrasubject repeatability of internal aberrometry obtained with a new integrated
      aberrometer.
AB  - PURPOSE: To evaluate the intrasubject repeatability of the internal aberrometry
      obtained with a new integrated aberrometer in a sample of normal eyes to assess
      its clinical usefulness. METHODS: Twenty-six healthy eyes of 26 participants,
      aged 20 to 50 years, were included in the study. All eyes achieved corrected
      distance visual acuity of 1.0 (Snellen decimal notation) and did not undergo
      previous ocular surgeries. Three consecutive measurements of internal aberrations
      were obtained with the KR-1W system (Topcon Corp) by an experienced examiner.
      Intrasubject repeatability for 4- and 6-mm pupils was evaluated by the within
      subject standard deviation (S(w)) and intraclass correlation coefficient (ICC).
      RESULTS: Low values of S(w) and values of ICC close to 1 were found for the 4-mm
      pupil astigmatism and for several aberrometric coefficients: primary spherical
      aberration and higher order, third order, and trefoil root-mean-square (RMS).
      Significant correlations of the S(w) for the 4-mm pupil higher order aberrations
      RMS with the magnitude of different aberrometric coefficients were found
      (r>=0.611, P<.01). In addition, tetrafoil RMS for 4-mm pupils correlated
      significantly with the S(w) for some higher order errors (r>=0.675, P<.01).
      Significantly larger values of S(w) for 6-mm pupils were found for trefoil
      (P<.01) and secondary astigmatism RMS (P=.02). CONCLUSIONS: The KR-1W provided
      repeatable measurements of internal astigmatism and some higher order
      aberrations, although consistency of such measurements appears to be limited by
      the level of aberration.

PMID- 21188959
TI  - Comparison of corneal tomography measurements using Galilei, Orbscan II, and
      Placido disk-based topographer systems.
AB  - PURPOSE: To evaluate agreement in keratometry readings and anterior and posterior
      elevation map measurements among the Galilei V4.01 (Ziemer), Orbscan IIz (Bausch
      & Lomb), and Corneal Map topographer (Costruzione Strumenti Oftalmici) systems.
      METHODS: This prospective comparative study comprised 184 eyes of 92 consecutive
      refractive surgery candidates who were simultaneously examined with the Galilei
      (dual Scheimpflug), Orbscan II (scanning-slit), and Corneal Map topographer
      (Placido disk-based) systems. Keratometry readings and anterior and posterior
      elevation map measurements were compared using analysis of variance and paired t
      test, respectively. RESULTS: Mean keratometry reading was 44.30 +/- 1.49 diopters
      (D), 44.11 +/- 1.47 D, and 44.60 +/- 1.56 D with the Galilei, Orbscan, and
      Corneal Map topographer, respectively. Despite a significant difference in mean
      keratometry (P<.001), the correlation among these three systems was strong. The
      maximum mean difference between two sets in simulated keratometry and astigmatism
      was <0.50 D. In the evaluation of anterior best-fit-sphere (BFS) and posterior
      BFS, the correlation between Galilei and Orbscan II was found to be 0.960 and
      0.947, respectively. Maximum anterior central elevation measured by Orbscan II
      and Galilei was 9.2 +/- 5.1 MUm and 3.2 +/- 1.8 MUm, respectively. Maximum
      posterior central elevation by Orbscan II and Galilei was 33.8 +/- 9.3 MUm and
      6.8 +/- 3.8 MUm, respectively. CONCLUSIONS: Despite significant differences in
      mean keratometry readings and anterior and posterior elevation measurements among
      the three systems, the keratometry readings can be used interchangeably, as this
      difference is not clinically significant.

PMID- 21188960
TI  - Intraocular pressure during corneal flap preparation: comparison among four
      femtosecond lasers in porcine eyes.
AB  - PURPOSE: To compare the course of intraocular pressure (IOP) during corneal flap
      preparation using four different femtosecond lasers in porcine globes. METHODS:
      Forty-eight (12 in each group) enucleated globes were successfully cannulated
      through the optic nerve. Intraocular pressure was measured continuously through
      the cannula during a normal lamellar flap creation (regular procedure) using four
      femtosecond lasers (IntraLase, Abbott Medical Optics; VisuMax, Carl Zeiss Meditec
      AG; Femtec, Technolas Perfect Vision; and Femto LDV, Ziemer Ophthalmic Systems
      AG). In an additional measurement (worst-case procedure), the patient interface
      was pressed against the globe with increasing force until the applanation
      maneuver was automatically aborted by those devices capable of doing so. RESULTS:
      During the regular procedure, the maximum IOP reached was 135+/-16 mmHg when
      using the Intra-Lase, 65+/-20 mmHg with the VisuMax, 205+/-32 mmHg with the
      Femtec, and 184+/-28 mmHg with the Femto LDV. During the worst-case procedure, a
      maximum IOP of 260+/-53 mmHg was reached with the IntraLase, 105+/-13 mmHg with
      the VisuMax, and 248+/-51 mmHg with the Femtec. CONCLUSIONS: There is
      considerable variation in IOP among the tested femtosecond lasers during a
      regular lamellar flap creation and during the worst-case procedure. The VisuMax
      femtosecond laser seems to cause the lowest IOP rise in both settings.

PMID- 21188961
TI  - Structural principles of semiconducting Group 14 clathrate frameworks.
AB  - We have performed a comprehensive theoretical investigation of the structural
      principles of semiconducting clathrate frameworks composed of the Group 14
      elements carbon, silicon, germanium, and tin. We have investigated the basic
      clathrate frameworks, together with their polytypes, intergrowth clathrate
      frameworks, and extended frameworks based on larger icosahedral building blocks.
      Quantum chemical calculations with the PBE0 hybrid density functional method
      provided a clear overview of the structural trends and electronic properties
      among the various clathrate frameworks. In agreement with previous experimental
      and theoretical studies, the clathrate II framework proved to be the
      energetically most favorable, but novel hexagonal polytypes of clathrate II also
      proved to be energetically very favorable. In the case of silicon, several of the
      studied clathrate frameworks possess direct and wide band gaps. The band
      structure diagrams and simulated powder X-ray patterns of the studied frameworks
      are provided and systematic preliminary evaluation of guest-occupied frameworks
      is conducted to shed light on the characteristics of novel, experimentally
      feasible clathrate compositions.

PMID- 21188962
TI  - Band-offset driven efficiency of the doping of SiGe core-shell nanowires.
AB  - Impurity doping of semiconducting nanowires has been predicted to become
      increasingly inefficient as the wire diameter is reduced, because impurity states
      get deeper due to quantum and dielectric confinement. We show that efficient n-
      and p-type doping can be achieved in SiGe core-shell nanowires as thin as 2 nm,
      taking advantage of the band offset at the Si/Ge interface. A one-dimensional
      electron (hole) gas is created at the band-edge and the carrier density is
      uniquely controlled by the impurity concentration with no need of thermal
      activation. Additionally, SiGe core-shell nanowires provide naturally the
      separation between the different types of carriers, electron and holes, and are
      ideally suited for photovoltaic applications.

PMID- 21188963
TI  - Elementary processes in nanowire growth.
AB  - We propose that many of the complex morpho-logical phenomena observed during
      nanowire growth arise from the interplay of just three elementary processes:
      facet growth, droplet statics, and the introduction of new facets. We incorporate
      these processes into an explicit model for the vapor-liquid-solid growth of fully
      faceted nanowires. In numerical simulations with this model, different conditions
      can lead to either growth of a free-standing wire or lateral growth where the
      catalyst droplet crawls along the surface. An external perturbation can cause the
      wire to kink into a different direction. Different growth conditions can also
      change the shape of the growth tip. All of these phenomena have been observed,
      and the model behavior is consistent with the experimental observations.

PMID- 21188964
TI  - Employing heavy metal-free colloidal quantum dots in solution-processed white
      light-emitting diodes.
AB  - We report in this communication the design and fabrication of solution-processed
      white light-emitting diodes (LEDs) containing a bilayer of heavy metal-free
      colloidal quantum dots (QDs) and polymer in the device active region. White
      electroluminescence was obtained in the LEDs by mixing the red emission of
      ZnCuInS/ZnS core/shell QDs and the blue-green emission of poly(N,N'-bis(4
      butylphenyl)-N,N'-bis(phenyl)benzidine). A high color rendering index of 92 was
      achieved as compared to a 5310 K blackbody reference by virtue of broadband
      emission of the QDs. The Commission Internationale de l'Eclairage chromaticity
      coordinates of the white LED output exhibit a distinctive bias dependence.
      Finally, aging of the white LEDs was studied, revealing the difference between
      the photochemical stabilities of the QDs and polymer molecules and the consequent
      effect on the color evolution of the LEDs.

PMID- 21188965
TI  - Heat profiling of three-dimensionally optically trapped gold nanoparticles using
      vesicle cargo release.
AB  - Irradiated metallic nanoparticles hold great promise as heat transducers in
      photothermal applications such as drug delivery assays or photothermal therapy.
      We quantify the temperature increase of individual gold nanoparticles trapped in
      three dimensions near lipid vesicles exhibiting temperature sensitive
      permeability. The surface temperature can increase by hundreds of degrees Celsius
      even at moderate laser powers. Also, there are significant differences of the
      heat profiles in two-dimensional and three-dimensional trapping assays.

PMID- 21188966
TI  - Solid-phase synthesis and biological evaluation of Joro spider toxin-4 from
      Nephila clavata.
AB  - Polyamine toxins from orb weaver spiders are attractive pharmacological tools
      particularly for studies of ionotropic glutamate (iGlu) receptors in the brain.
      These polyamine toxins are biosynthesized in a combinatorial manner, providing a
      plethora of related, but structurally complex toxins to be exploited in
      biological studies. Here, we have used solid-phase synthetic methodology for the
      efficient synthesis of Joro spider toxin-4 (JSTX-4) (1) from Nephila clavata,
      providing sufficient amounts of the toxin for biological evaluation at iGlu
      receptor subtypes using electrophysiology. Biological evaluation revealed that
      JSTX-4 inhibits iGlu receptors only in high MUM concentrations, thereby being
      substantially less potent than structurally related polyamine toxins.

PMID- 21188967
TI  - Various Au nanoparticle organizations fabricated through SiO2 monomer induced
      self-assembly.
AB  - A novel method has been developed to fabricate the assembly of Au colloidal
      nanoparticles (NPs) using SiO(2) monomers. The key strategy was the use of a
      controlled sol-gel procedure including hydrolysis, deposition, and condensation
      of tetraethyl orthosilicate (TEOS). Namely, the assembly of Au NPs was created by
      the anisotropic deposition of SiO(2) monomers and subsequent permanent fixing by
      the growth of a SiO(2) shell. Various assemblies of Au NPs such as dimer, trimer,
      and pearl-chain morphology were fabricated by systematically changing the
      concentration and injection speed of TEOS. A longitudinal plasmon resonance band
      was observed as a result of the assembly of Au NPs and can be tuned from visible
      to near-infrared by altering the length of pearl-chain morphology. In addition,
      single Au NP was homogeneously coated with a SiO(2) shell by means of controlling
      the deposition rate of SiO(2) monomers during a Stober synthesis without the use
      of a silane coupling agent or bulk polymer as the surface primer to render the Au
      surface vitreophilic. The Au NPs (mean size 11.4 nm in diameter) were thus
      encapsulated into SiO(2) beads with a wide range of sizes (from 20 to 50 nm in
      diameter). These pure SiO(2)-coated Au beads with tunable shell thickness should
      be crucial for biosensors, particularly as Raman-tag particles.

PMID- 21188968
TI  - Catalytic asymmetric allylation of 3,4-dihydroisoquinolines and its application
      to the synthesis of isoquinoline alkaloids.
AB  - A catalytic asymmetric allylation of 3,4-dihydroisoquinoline was carried out with
      allyltrimethoxylsilane-Cu as the nucleophile in the presence of DTBM-SEGPHOS as
      the chiral ligand to afford corresponding chiral 1-allyltetrahydroisoquinoline
      derivatives in good yield and stereoselectivity. The allyl adduct thus obtained
      was applied to the synthesis of several isoquinoline alkaloids such as crispine A
      and homolaudanosine. The reaction was further used for the synthesis of the
      isoquinoline moiety of schulzeine A.

PMID- 21188969
TI  - Asymmetric organocatalytic double-conjugate addition of malononitrile to
      dienones: efficient synthesis of optically active cyclohexanones.
AB  - 9-Amino-9-deoxyepiquinine efficiently catalyzed the double-conjugate addition of
      malononitrile to dienones. A number of 1,1,2,6-tetrasubstituted cyclohexanones
      were prepared in good yields, diastereoselectivities, and excellent
      enantioselectivities.

PMID- 21188970
TI  - Role of pseudoephedrine as chiral auxiliary in the "acetate-type" aldol reaction
      with chiral aldehydes; asymmetric synthesis of highly functionalized chiral
      building blocks.
AB  - We have studied in depth the aldol reaction between acetamide enolates and chiral
      alpha-heterosubstituted aldehydes using pseudoephedrine as chiral auxiliary under
      double stereodifferentiation conditions, showing that high diastereoselectivities
      can only be achieved under the matched combination of reagents and provided that
      the alpha-heteroatom-containing substituent of the chiral aldehyde is
      conveniently protected. Moreover, the obtained highly functionalized aldols have
      been employed as very useful starting materials for the stereocontrolled
      preparation of other interesting compounds and chiral building blocks such as
      pyrrolidines, indolizidines, and densely functionalized beta-hydroxy and beta
      amino ketones using simple and high-yielding methodologies.

PMID- 21188971
TI  - Determining nanocapillary geometry from electrochemical impedance spectroscopy
      using a variable topology network circuit model.
AB  - Solid-state nanopores and nanocapillaries find increasing use in a variety of
      applications including DNA sequencing, synthetic nanopores, next-generation
      membranes for water purification, and other nanofluidic structures. This paper
      develops the use of electrochemical impedance spectroscopy to determine the
      geometry of nanocapillaries. A network equivalent circuit element is derived to
      include the effects of the capacitive double layer inside the nanocapillaries as
      well as the influence of varying nanocapillary radius. This variable topology
      function is similar to the finite Warburg impedance in certain limits. Analytical
      expressions for several different nanocapillary shapes are derived. The functions
      are evaluated to determine how the impedance signals will change with different
      nanocapillary aspect ratios and different degrees of constriction or inflation at
      the capillary center. Next, the complex impedance spectrum of a nanocapillary
      array membrane is measured at varying concentrations of electrolyte to separate
      the effects of nanocapillary double layer capacitance from those of nanocapillary
      geometry. The variable topology equivalent circuit element model of the
      nanocapillary is used in an equivalent circuit model that included contributions
      from the membrane and the measurement apparatus. The resulting values are
      consistent with the manufacturer's specified tolerances of the nanocapillary
      geometry. It is demonstrated that electrochemical impedance spectroscopy can be
      used as a tool for in situ determination of the geometry of nanocapillaries.

PMID- 21188972
TI  - Copper(II)chloride-mediated cyclization reaction of N-alkoxy-ortho
      alkynylbenzamides.
AB  - A regioselective intramolecular cyclization/halogenation reaction of N-alkoxy-o
      alkynylbenzamides with CuCl(2)/NCS was developed. The corresponding 3
      (chloromethylene)isobenzofuran-1-ones were exclusively obtained via 5-exo-dig
      cyclization in moderate to excellent yields within 0.5-1 h. This approach has
      been successfully used to synthesize a biaryl compound by the Suzuki-Miyaura
      reaction.

PMID- 21188973
TI  - Total synthesis of (+)-isatisine A.
AB  - Total synthesis of (+)-isatisine A is described based on the application of a
      silyl-directed Mukaiyama-type [3 + 2]-annulation for the preparation of a fully
      substituted furan core. The indole branch forming the quaternary carbon center at
      C2 was constructed by addition to an intermediate N-acyliminium ion derived from
      aminal 4. In addition, the fused tetracyclic framework including furan core was
      built up using modified Buchwald amidation conditions.

PMID- 21188974
TI  - Protein reactivity of natural product-derived gamma-butyrolactones.
AB  - The discovery of novel and unique target-drug pairs for the treatment of human
      diseases such as cancer and bacterial infections is an urgent goal of chemical
      and pharmaceutical sciences. Natural products represent an inspiring source of
      compounds for designing chemical biology methods with applications in target
      identification and characterization. Inspired by the huge structural diversity of
      gamma-butyrolactones, which constitute up to 10% of all known compounds of
      natural origin, we extended the "activity-based protein profiling" (ABPP) target
      identification technology to this promising and so far unexplored natural
      compound class. We designed and synthesized a comprehensive set of natural
      product-derived gamma-lactones and thiolactones that varied in protein
      reactivity. Several important bacterial enzymes that are involved in diverse
      cellular functions such as metabolism (dihydrolipoyl dehydrogenase and 6
      phosphofructokinase), cell wall biosynthesis (MurA1 and MurA2), and protein
      folding (trigger factors) were obtained. Especially protein folding in bacteria
      could represent a novel strategy for antibiotic intervention and requires
      chemical tools for characterization and inhibition. Future studies that extend
      structural modifications to protein reactive alpha-methylene-gamma-butyrolactone
      as well as to reversible binding gamma-lactones and thiolactones will reveal if
      this premise holds true.

PMID- 21188975
TI  - Lauroside B, a megastigmane glycoside from Laurus nobilis (bay laurel) leaves,
      induces apoptosis in human melanoma cell lines by inhibiting NF-kappaB
      activation.
AB  - Malignant melanoma is a highly aggressive tumor that frequently resists
      chemotherapy, so the search for new agents for its treatment is of great
      importance. In the present study, the antiproliferative propensity against human
      melanoma cell lines of lauroside B (1), a megastigmane glycoside isolated from
      Laurus nobilis (bay laurel) leaves, was investigated. This compound suppressed
      the proliferation of three human melanoma cell lines, namely, A375, WM115, and SK
      Mel-28. The 1-induced inhibition of human melanoma cell proliferation was due to
      the induction of apoptosis, as demonstrated by FACS analysis with annexin V/PI
      staining and confirmed by activation of caspase-3 and by the cleavage of poly(ADP
      ribose) polymerase (PARP). Growing evidence implicates NF-kappaB as an important
      contributor to metastasis and increased chemoresistance of melanoma. Thus, it was
      hypothesized that 1-induced apoptosis could be associated with suppression of NF
      kappaB activation. The results showed that exposure of human melanoma cells to 1
      inhibited IkappaB-alpha degradation and constitutive NF-kappaB DNA-binding
      activity as well as the expression, regulated by NF-kappaB, of two antiapoptotic
      genes, XIAP and c-FLIP. Induction of apoptosis by 1 in human aggressive melanoma
      cell lines has a potential high biological value.

PMID- 21188976
TI  - Water desalination using carbon-nanotube-enhanced membrane distillation.
AB  - Carbon nanotube (CNT) enhanced membrane distillation is presented for water
      desalination. It is demonstrated that the immobilization of the CNTs in the pores
      of a hydrophobic membrane favorably alters the water-membrane interactions to
      promote vapor permeability while preventing liquid penetration into the membrane
      pores. For a salt concentration of 34 000 mg L(-1) and at 80  degrees C, the
      nanotube incorporation led to 1.85 and 15 times increase in flux and salt
      reduction, respectively.

PMID- 21188977
TI  - Syntheses, structures, and magnetic properties of Np3S5 and Np3Se5.
AB  - Black prisms of Np(3)Q(5) (Q = S, Se) have been synthesized by the stoichiometric
      reactions between Np and Q at 1173 K in a CsCl flux. The structures of these
      compounds were characterized by single-crystal X-ray diffraction methods. The
      Np(3)Q(5) compounds are isostructural with U(3)Q(5). The structure of Np(3)Q(5)
      is constructed from layers of Np(1)Q(8) distorted bicapped trigonal prisms that
      share faces with each other on bc planes. Each Np(1)Q(8) layer further shares
      Q(2) edges with two adjacent identical neighbors to form a three-dimensional
      framework. The space inside each channel within this framework is filled by one
      single edge-sharing Np(2)Q(7) distorted 7-octahedron chain running along the b
      axis. Magnetic susceptibility measurements show that Np(3)S(5) and Np(3)Se(5)
      have antiferromagnetic orderings at 35(1) and 36(1) K, respectively. Above the
      magnetic ordering temperatures, both Np(3)S(5) and Np(3)Se(5) behave as typical
      Curie-Weiss paramagnets. The effective moments obtained from the fit of the
      magnetic data to a modified Curie-Weiss law over the temperature range 70 to 300
      K are 2.7(2) MU(B) (Np(3)S(5)) and 2.9(2) MU(B) (Np(3)Se(5)).

PMID- 21188978
TI  - Crystal chemistry and stability of "Li7La3Zr2O12" garnet: a fast lithium-ion
      conductor.
AB  - Recent research has shown that certain Li-oxide garnets with high mechanical,
      thermal, chemical, and electrochemical stability are excellent fast Li-ion
      conductors. However, the detailed crystal chemistry of Li-oxide garnets is not
      well understood, nor is the relationship between crystal chemistry and conduction
      behavior. An investigation was undertaken to understand the crystal chemical and
      structural properties, as well as the stability relations, of
      Li(7)La(3)Zr(2)O(12) garnet, which is the best conducting Li-oxide garnet
      discovered to date. Two different sintering methods produced Li-oxide garnet but
      with slightly different compositions and different grain sizes. The first
      sintering method, involving ceramic crucibles in initial synthesis steps and
      later sealed Pt capsules, produced single crystals up to roughly 100 MUm in size.
      Electron microprobe and laser ablation inductively coupled plasma mass
      spectrometry (ICP-MS) measurements show small amounts of Al in the garnet,
      probably originating from the crucibles. The crystal structure of this phase was
      determined using X-ray single-crystal diffraction every 100 K from 100 K up to
      500 K. The crystals are cubic with space group Ia3d at all temperatures. The
      atomic displacement parameters and Li-site occupancies were measured. Li atoms
      could be located on at least two structural sites that are partially occupied,
      while other Li atoms in the structure appear to be delocalized. (27)Al NMR
      spectra show two main resonances that are interpreted as indicating that minor Al
      occurs on the two different Li sites. Li NMR spectra show a single narrow
      resonance at 1.2-1.3 ppm indicating fast Li-ion diffusion at room temperature.
      The chemical shift value indicates that the Li atoms spend most of their time at
      the tetrahedrally coordinated C (24d) site. The second synthesis method, using
      solely Pt crucibles during sintering, produced fine-grained Li(7)La(3)Zr(2)O(12)
      crystals. This material was studied by X-ray powder diffraction at different
      temperatures between 25 and 200  degrees C. This phase is tetragonal at room
      temperature and undergoes a phase transition to a cubic phase between 100 and 150
      degrees C. Cubic "Li(7)La(3)Zr(2)O(12)" may be stabilized at ambient conditions
      relative to its slightly less conducting tetragonal modification via small
      amounts of Al(3+). Several crystal chemical properties appear to promote the high
      Li-ion conductivity in cubic Al-containing Li(7)La(3)Zr(2)O(12). They are (i)
      isotropic three-dimensional Li-diffusion pathways, (ii) closely spaced Li sites
      and Li delocalization that allow for easy and fast Li diffusion, and (iii) low
      occupancies at the Li sites, which may also be enhanced by the heterovalent
      substitution Al(3+) <=> 3Li.

PMID- 21188979
TI  - Immobilized boron-centered heteroscorpionates: heterocycle metathesis and
      coordination chemistry.
AB  - The preparation of a resin-supported boron-scorpionate ligand and its nickel(II)
      coordination complexes are reported. The supported ligand is prepared as its
      potassium salt, making it a general reagent suitable for chelation of any
      transition metal ion. Resin-immobilized benzotriazole (Bead-btz) reacted cleanly
      with KTp* (Tp* = hydrotris(3,5-dimethylpyrazolyl)borate) by heterocycle
      metathesis in warm dimethylformamide (DMF) to yield bead-Tp'K, {resin
      btz(H)B(pz*)(2)}K. Significantly, bead-Tp'K readily bound nickel(II) from simple
      salts with minimal leaching of the nickel ion. Bead-Tp'NiNO(3) reacts further
      with cysteine thiolate (ethyl ester), imparting the deep green color to the beads
      characteristic of a Tp(R)NiCysEt coordination sphere. Bead-Tp'NiCysEt exhibited
      an oxygen sensitivity similar to Tp*NiCysEt in solution (Inorg. Chem. 1999, p
      5690) and also independently verified for a selenocystamine analogue,
      Tp*NiSeCysAm. Addition of fresh cysteine thiolate ethyl ester to oxidized bead
      Tp'NiCysEt reproduced the original green color. Heterocycle metathesis was also
      used to prepare KTp' as a white solid. Reaction with nickel(II) gave (Tp')(2)Ni,
      separable into two different isomers. The air-sensitive molybdenum(0) complex,
      [PPh(4)][Tp'Mo(CO)(3)], was also prepared and the C(s) complex symmetry
      demonstrated by infrared and (13)C NMR spectroscopies. Immobilized TpmMo(CO)(3)
      was prepared from the previously reported resin-supported tris(pyrazolyl)methane.
      In contrast to its weak coordination of nickel(II) (Inorg. Chem. 2009, p 3535),
      bead-Tpm proved a strong chelate toward this second row metal. The supported
      scorpionates described here should find use in studies of selective metal-protein
      binding, metalloprotein modeling, and heterogeneous catalysis, and render such
      scorpionate applications amenable to combinatorial methods.

PMID- 21188980
TI  - Experimental and theoretical Mossbauer study of an extended family of [Fe8(MU4
      O)4(MU-4-R-px)12X4] clusters.
AB  - Six [Fe(8)(MU(4)-O)(4)(MU-4-R-pyrazolato)(12)X(4)] complexes containing an
      identical Fe(8)(MU(4)-O)(4) core have been structurally characterized and studied
      by Mossbauer spectroscopy. In each case, an inner MU(4)-O bridged Fe(III) cubane
      core is surrounded by four trigonal bipyramidal iron centers, the two distinct
      sites occurring in a 1:1 ratio. The Mossbauer spectrum of each of the clusters
      consists of two quadrupole doublets, which, with one exception (X = NCS, R = H),
      overlap to give three absorption lines. The systematic variation of X and R
      causes significant changes in the Mossbauer spectra. A comparison with values for
      the same clusters computed using density functional theory allows us to establish
      an unequivocal assignment of these peaks in terms of a nested model for the
      overlapping doublets. The changes in Mossbauer parameters (both experimental and
      computed) for the 1-electron reduced species [Fe(8)(MU(4)-O)(4)(MU-4-Cl
      pyrazolato)(12)Cl(4)](-) are consistent with a redox event that is localized
      within the cubane core.

PMID- 21188981
TI  - Copper(I) coordination polymers of N,N'-bis[3-(methylthio)propyl]pyromellitic
      diimide: crystal transformation and solvatochromism by halogen-pi interactions.
AB  - Four copper(I) coordination polymers with ligand N,N'-bis[3
      (methylthio)propyl]pyromellitic diimide (L), [Cu(2)I(2)L(2)](n) (1),
      [Cu(2)I(2)L(2)](n) (2), [Cu(2)I(2)L](n) (3), and {[Cu(2)I(2)L(2)].CH(2)Cl(2)}(n)
      (4), have been successfully synthesized and structurally characterized by single
      crystal X-ray diffraction. Structural transformations between the polymers were
      controlled by the appropriate solvent composition, mole ratio, or temperature.
      When a 1:1 CuI/L ratio was employed, dimorphic products, 1 and 2, based on a
      rhomboid Cu(2)I(2) cluster were obtained from an acetonitrile solution and from a
      dichloromethane/acetonitrile solution with ultrasonication, respectively. When a
      1:2 CuI/L ratio was employed, polymer 3 based on infinite stair-step polymer
      (CuI)(infinity) was crystallized. Crystalline product 4 was obtained by the
      transformation of 1 in a mixed-solvent system with a 1:5
      acetonitrile/dichloromethane ratio. Polymers 1-4 were transformed into polymer 3
      at 197  degrees C. X-ray structures of 2-4 show short distances (3.406-3.667 A)
      between halogens (I(-) and Cl) and aromatic rings. 1 and 4 show solvatochromism;
      upon inclusion of the colorless electron donor CH(2)Cl(2), the red color changes
      as a result of the formation of a chloride-pi charge-transfer complex 4 of a pale
      colored electron acceptor, 1. Therefore, the origin of the red color from 2 and 3
      is also assigned as iodide-to-electron-deficient aromatic pi charge transfer.

PMID- 21188983
TI  - Nature of bonding in terminal borylene, alylene, and gallylene complexes of
      vanadium and niobium [(eta(5)-C5H5)(CO)3M(ENR2)] (M = V, Nb; E = B, Al, Ga; R =
      CH3, SiH3, CMe3, SiMe3): a DFT study.
AB  - Density functional theory calculations have been performed for the terminal
      borylene, alylene, and gallylene complexes [(eta(5)-C(5)H(5))(CO)(3)M(ENR(2))] (M
      = V, Nb; E = B, Al, Ga; R = CH(3), SiH(3), CMe(3), SiMe(3)) using the exchange
      correlation functional BP86. The calculated geometry parameters of vanadium
      borylene complex [(eta(5)-C(5)H(5))(CO)(3)V{BN(SiMe(3))(2)}] are in excellent
      agreement with their available experimental values. The M-B bonds in the borylene
      complexes have partial M-B double-bond character, and the B-N bonds are nearly
      B?N double bonds. On the other hand, the M-E bonds in the studied metal alylene
      and gallylene complexes represent M-E single bonds with a very small M-E pi
      orbital contribution, and the Al-N and Ga-N bonds in the complexes have partial
      double-bond character. The orbital interactions between metal and ENR(2) in
      [(eta(5)-C(5)H(5))(CO)(3)M(ENR(2))] arise mainly from M <- ENR(2) sigma donation.
      The pi-bonding contribution is, in all complexes, much smaller. The contributions
      of the electrostatic interactions DeltaE(elstat) are significantly larger in all
      borylene, alylene, and gallylene complexes than the covalent bonding DeltaE(orb);
      that is, the M-ENR(2) bonding in the complexes has a greater degree of ionic
      character.

PMID- 21188982
TI  - Comparative study of mono- and dinuclear complexes of late 3d-metal chlorides
      with N,N-dimethylformamide in the gas phase.
AB  - Mono- and binuclear complexes of N,N-dimethylformamide (DMF) with chlorides of
      the divalent, late 3d metals M = Co, Ni, Cu, and Zn are investigated by means of
      electrospray ionization (ESI). Specifically, ESI leads to monocations of the type
      [(DMF)(n)MCl](+) and [(DMF)(n)M(2)Cl(3)](+), of which the species with n = 2 and
      3 were selected for in-depth studies. The latter include collision-induced
      dissociation experiments, gas-phase infrared spectroscopy, and calculations using
      density functional theory. The mononuclear complexes [(DMF)(n)MCl](+) almost
      exclusively lose neutral DMF upon collisional activation with the notable
      exception of the copper complex, for which also a reduction from Cu(II) to Cu(I)
      concomitant with the release of atomic chlorine is observed. For the dinuclear
      clusters, there exists a competition between loss of a DMF ligand and cluster
      degradation via loss of neutral MCl(2) with decreasing cluster stability from
      cobalt to zinc. For the specific case of [(DMF)(n)ZnCl](+) and
      [(DMF)(n)Zn(2)Cl(3)](+), ion-mobility mass spectrometry indicates the existence
      of two isomeric cluster ions in the case of [(DMF)(2)Zn(2)Cl(3)](+) which
      corroborates parallel theoretical predictions.

PMID- 21188984
TI  - [Mn(C4H10ON)(H2O)][Fe(CN)6]: a three-dimensional cyanide-bridged ferrimagnet with
      a morpholine ligand.
AB  - The reaction of the Mn(II) and [Fe(CN)(6)](3-) ions in the presence of morpholine
      at 90  degrees C yields a new cyanide-bridged three-dimensional (3D) assembly,
      showing a ferrimagnetic ordering, frequency-dependent ac susceptibility, and
      hysteresis loops below 14.8 K. In addition, our feasible route to rationally
      design and prepare this new molecule-based ferrimagnet promises to provide new 3D
      cyanide-bridged complexes in the future research.

PMID- 21188985
TI  - Near-infrared-emitting phthalocyanines. A combined experimental and density
      functional theory study of the structural, optical, and photophysical properties
      of Pd(II) and Pt(II) alpha-butoxyphthalocyanines.
AB  - The structural, optical, and photophysical properties of 1,4,8,11,15,18,22,25
      octabutoxyphthalocyaninato-palladium(II), PdPc(OBu)(8), and the newly synthesized
      platinum analogue PtPc(OBu)(8) are investigated combining X-ray crystallography,
      static and transient absorption spectroscopy, and relativistic zeroth-order
      regular approximation (ZORA) Density Functional Theory (DFT)/Time Dependent DFT
      (TDDFT) calculations where spin-orbit coupling (SOC) effects are explicitly
      considered. The results are compared to those previously reported for
      NiPc(OBu)(8) (J. Phys. Chem. A 2005, 109, 2078) in an effort to highlight the
      effect of the central metal on the structural and photophysical properties of the
      group 10 transition metal octabutoxyphthalocyanines. Different from the nickel
      analogue, PdPc(OBu)(8) and PtPc(OBu)(8) show a modest and irregular saddling
      distortion of the macrocycle, but share with the first member of the group
      similar UV-vis spectra, with the deep red and intense Q-band absorption
      experiencing a blue shift down the group, as observed in virtually all
      tetrapyrrolic complexes of this triad. The blue shift of the Q-band along the
      MPc(OBu)(8) (M = Ni, Pd, Pt) series is interpreted on the basis of the metal
      induced electronic structure changes. Besides the intense deep red absorption,
      the title complexes exhibit a distinct near-infrared (NIR) absorption due to a
      transition to the double-group 1E (pi,pi*) state, which is dominated by the
      lowest single-group (3)E (pi,pi*) state. Unlike NiPc(OBu)(8), which is
      nonluminescent, PdPc(OBu)(8) and PtPc(OBu)(8) show both deep red fluorescence
      emission and NIR phosphorescence emission. Transient absorption experiments and
      relativistic spin-orbit TDDFT calculations consistently indicate that
      fluorescence and phosphorescence emissions occur from the S(1)(pi,pi*) and
      T(1)(pi,pi*) states, respectively, the latter being directly populated from the
      former, and the triplet state decays directly to the S(0) surface (the triplet
      lifetime in deaerated benzene solution was 3.04 MUs for Pd and 0.55 MUs for Pt).
      Owing to their triplet properties, PdPc(OBu)(8) and PtPc(OBu)(8) have potential
      for use in photodynamic therapy (PDT) and are potential candidates for NIR light
      emitting diodes or NIR emitting probes.

PMID- 21188986
TI  - Silver porous nanotube built three-dimensional films with structural tunability
      based on the nanofiber template-plasma etching strategy.
AB  - A facile and high-throughput strategy is presented to fabricate three-dimensional
      (3D) hierarchically porous Ag films, with clean surfaces, via plasma etching Ag
      coated electrospun nanofiber template. The films are built of Ag porous nanotubes
      and are homogeneous in macro-size but rough and porous in nanoscale. Each
      nanotube-block is micro/nanostructured with evenly distributed nanopores on the
      tube walls. The film architecture (or the shape, arrangement, and distribution
      density of porous nanotubes; the number and size of nanopores) can be easily
      controlled by the nanofiber-template configuration, Ag coating, and plasma
      etching conditions. Such hierarchically porous films could be very useful, such
      as in catalysis, sensors, and nanodevices. They have exhibited significantly
      structurally enhanced surface-enhanced Raman scattering performance with good
      stability and reproduction, and shown the possibility of molecule-level
      detection. Also, the strategy is universal for fabricating other hierarchically
      structured 3D metal porous films, such as porous Ag hollow sphere arrays.

PMID- 21188987
TI  - Dispersions of nanoclays of different shapes into aqueous and solid biopolymeric
      matrices. Extended physicochemical study.
AB  - Dispersions of nanofillers into aqueous and solid biopolymeric matrices were
      studied from the physicochemical viewpoint. This work was carried out based on
      the idea that the combination of biopolymers, derived from renewable resources,
      and nanofiller, environmentally friendly, may form a new generation of
      nanomaterials with excellent and unique properties at low cost. To this purpose,
      two pectins with different degrees of methyl esterification and nanoclays like
      halloysite and laponite RD were selected. The thermodynamic and structural
      studies on the aqueous mixtures of pectin and nanoclay were able to discriminate
      the interactions, which control the adsorption of pectin onto the filler and the
      aggregation of both pectin and clay particles. The gained insights were useful to
      interpret the mesoscopic structure of the nanocomposites (prepared from the
      aqueous mixtures by means of the casting method) evidenced by SEM, thermal
      stability, tensile properties, and transparency investigations. The attained
      knowledge represents a basic point for designing new hybrid nanostructures in
      both the aqueous and the solid phase for specific purposes.

PMID- 21188988
TI  - Effect of carbon surface modification with dimethylamine on reactive adsorption
      of NO(x).
AB  - The wood-based activated carbon, either as received or oxidized with nitric acid,
      was exposed to dimethylamine vapors. This modification was expected to introduce
      nitrogen groups. Then, the modified samples were used as adsorbents of NO(2)
      under dynamic conditions. Both NO(2) breakthrough curves and the NO concentration
      curves were recorded. The samples before and after exposure to NO(2) were
      characterized using adsorption of nitrogen, elemental analysis, potentiometric
      titration, FTIR, and thermal analysis. Modifications with amines resulted in an
      increase in NO(2) adsorption and in a decrease in NO emission. The effects were
      more visible when oxidation was used as a pretreatment of the carbon surface.
      This process increased the incorporation of nitrogen to the carbon matrix via
      acid-based reactions resulting in the formation of amides and amine carboxylic
      salts. Besides this, dimethylamine was strongly adsorbed on the carbon surface
      via hydrogen bonding with oxygen-containing groups. When the samples were exposed
      to nitrogen dioxide, there was an indication that nitramine and nitrosoamine were
      formed in the reactions of NO(2) with either amides or amines. In the reactions
      of amines with NO, nitrosoamines are the likely products. As a next step, the
      surface of the carbon matrix is reoxidized by NO(2), which is accompanied by the
      release of NO.

PMID- 21188989
TI  - A straightforward way to form close-packed TiO2 particle monolayers at an
      air/water interface.
AB  - The aim of this study was to analyze if and how monolayers of TiO(2) particles
      could be directly formed at the air/water interface and if these monolayers could
      be transferred to a solid surface. TiO(2) particles with diameters of 300 nm, 500
      nm, 1 MUm, 5 MUm, 10 MUm, and 20 MUm formed stable monolayers at pH 2. At low
      surface pressures, the particles formed small two-dimensional aggregates.
      Particles up to a radius of 5 MUm displayed close packing at increased surface
      pressures. Particles of 10 MUm radius formed a loose network, which is attributed
      to the strong adhesion caused by the weight-induced lateral capillary attraction.
      Every monolayer of particles could be transformed to a solid surface by the
      Langmuir-Blodgett deposition. At pH 6 or 11, the particles did not form stable
      monolayers at the air/water interface. They were instead dispersed in the aqueous
      phase and eventually sank to the bottom of the trough. At pH 11 the monolayer
      could, however, be stabilized by the addition of salt (0.5 M NaCl). The results
      are interpreted based on a changed wettability of the particles depending on pH
      and salt concentration.

PMID- 21188990
TI  - Laser ablation direct writing of metal nanoparticles for hydrogen and humidity
      sensors.
AB  - A UV pulsed laser writing technique to fabricate metal nanoparticle patterns on
      low-cost substrates is demonstrated. We use this process to directly write
      nanoparticle gas sensors, which operate via quantum tunnelling of electrons at
      room temperature across the device. The advantages of this method are no
      lithography requirements, high precision nanoparticle placement, and room
      temperature processing in atmospheric conditions. Palladium-based nanoparticle
      sensors are tested for the detection of water vapor and hydrogen within
      controlled environmental chambers. The electrical conduction mechanism
      responsible for the very high sensitivity of the devices is discussed with regard
      to the interparticle capacitance and the tunnelling resistance.

PMID- 21188991
TI  - Freeze-fracture TEM imaging of robust order in swollen phases of amphiphilic
      diblock copolymers.
AB  - We report on the structures exhibited by two different diblock poly(styrene)-b
      poly(acrylic acid) (PS-b-PAA) copolymers in water, a selective solvent. Using a
      combination of X-ray scattering and freeze fracture-transmission electron
      microscopy (FF-TEM), we show that these structures can be widely swollen while
      retaining their initial morphology and a high degree of long-range order. The
      analysis of the FF-TEM pictures also evidences the presence of water crystallites
      of regular size and shape within the confined water domains. We relate the growth
      of these crystallites to the high local ionic strength of the water swelling the
      PAA brushes. Moreover, the confinement of the crystallites growth shows that the
      swollen phases have a very robust structure, potentially useful for confining
      colloidal particles.

PMID- 21188992
TI  - Adsorption of protein-surfactant complexes at the water/oil interface.
AB  - Interfacial tension measurements have been performed at the water/hexane
      interface on mixtures of the bovine milk protein beta-lactoglobulin and
      positively charged cationic surfactants (alkytrimethylammonium bromides). The
      addition of surfactants with different chain lengths leads to the formation of
      protein-surfactant complexes with different adsorption properties as compared to
      those of the single protein. In this study, the formation of complexes has been
      observed clearly for protein-long chain surfactant (TTAB and CTAB) mixtures,
      which has shown in addition to specific electrostatic interactions the relevance
      of hydrophobic interactions between surfactant molecules and the protein. The
      modeling of interfacial tension data by using a mixed adsorption model provides a
      quantitative understanding of the mixture behavior. Indeed, the value of the
      adsorption constant of the protein obtained in the presence of surfactants has
      strongly varied as compared to the single protein. Actually, this parameter which
      represents the affinity of the molecule for the interface is representative of
      the hydrophobic character of the compound and so of its surface activity. Even if
      a more hydrophobic and more surface active protein-surfactant complex has been
      formed, the replacement of this complex from the interface by surfactants close
      to their cmc was observed.

PMID- 21188993
TI  - Coexisting aggregates in mixed aerosol OT and cholesterol microemulsions.
AB  - Dynamic light scattering and NMR spectroscopic experimental evidence suggest the
      coexistence of two compositionally different self-assembled particles in
      solution. The self-assembled particles form in solutions containing water,
      Aerosol OT (AOT, sodium bis(2-ethylhexyl) sulfosuccinate) surfactant, and
      cholesterol in cyclohexane. In a similar series of studies carried out in 1
      octanol only one aggregate type, that is, reverse micelles, is observed. Dynamic
      light scattering measurements reveal the presence of two different types of
      aggregates in the microemulsions formed in cyclohexane, demonstrating the
      coexistence of two compositionally distinct structures with very similar Gibbs
      energies. One particle type consists of standard AOT reverse micelles while the
      second type of particle consists of submicellar aggregates including cholesterol
      as well as small amounts of AOT and water. In microemulsions employing 1-octanol
      as the continuous medium, AOT reverse micelles form in a dispersed solution of
      cholesterol in 1-octanol. Although the size distribution of self-assembled
      particles is well-known for many different systems, evidence for simultaneous
      formation of two distinctly sized particles in solution that are chemically
      different is unprecedented. The ability to form microemulsion solutions that
      contain coexisting particles may have important applications in drug formulation
      and administration, particularly as applied to drug delivery using cholesterol as
      a targeting agent.

PMID- 21188994
TI  - Polyunsaturated and saturated phospholipids in mixed bilayers: a study from the
      molecular scale to the lateral lipid organization.
AB  - Polyunsaturated lipids are remarkably flexible molecules, with a great influence
      on the membrane structure and dynamics, affecting from mechanical properties to
      domain segregation. In this work, we studied phospholipid mixtures of
      dipalmitoylphosphatidylcholine (DPPC) and diunsaturated phosphatidylcholine
      lipids (diunsPC) of different lengths, by means of molecular dynamic simulations
      of a coarse-grained interaction model. These diunsPC:DPPC binary mixtures show
      nonideal behavior characterized by one mixed phase with composition fluctuations
      on a length scale of nanometers. Motivated by this observation, we studied
      comprehensively the characteristics of molecular structure as a function of the
      compositional gradient. We analyzed orientational order profiles, density
      distributions, and pair-pair correlation functions between the molecule residues.
      We observed that, in diunsPC-enriched regions, DPPC tails become expanded and
      disordered, especially toward the membrane center. On the other hand, in the more
      condensed DPPC-enriched patches, diunsaturated acyl chains become displaced
      toward the interface instead of stretching along the membrane normal. From the
      comparison of the two diunsPC lipids of different tail length, we measured that
      the presence of a longer terminal saturated segment induces better mixing with
      DPPC, and most interestingly eliminates the up-down composition correlation
      measured with the shorter tail-diunsPC. At molecular level, there is a reduced
      redistribution of densities and changes in the local order as a function of
      composition. We interpret these results as indicative that the packing
      incompatibility between polyunsaturated and saturated lipids rules their mixing
      behavior.

PMID- 21188995
TI  - Structural evolution of perfluoro-pentacene films on Ag(111): transition from 2D
      to 3D growth.
AB  - The structural evolution and thermal stability of perfluoro-pentacene (PF-PEN)
      thin films on Ag(111) have been studied by means of low-temperature scanning
      tunnelling microscopy (STM), low-energy electron diffraction (LEED), atomic force
      microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and thermal desorption
      spectroscopy (TDS). Well-defined monolayer films can be prepared by utilizing the
      different adsorption energy of mono- and multilayer films and selectively
      desorbing multilayers upon careful heating at 380 K, whereas at temperatures
      above 400 K, a dissociation occurs. In the first monolayer, the molecules adopt a
      planar adsorption geometry and form a well-ordered commensurate (6 * 3)
      superstructure where molecules are uniformly oriented with their long axis along
      the <110> azimuth. This molecular orientation is also maintained in the second
      layer, where molecules exhibit a staggered packing motif, whereas further
      deposition leads to the formation of isolated, tall islands. Moreover, on smooth
      silver surfaces with extended terraces, growth of PF-PEN onto beforehand prepared
      long-range ordered monolayer films at elevated temperature leads to needle-like
      islands that are uniformly aligned at substrate steps along <110> azimuth
      directions.

PMID- 21188996
TI  - Programmed two-dimensional self-assembly of multiple DNA origami jigsaw pieces.
AB  - We demonstrate a novel strategy of self-assembly to scale up origami structures
      in two-dimensional (2D) space using multiple origami structures, named "2D DNA
      jigsaw pieces", with a specially designed shape. For execution of 2D self
      assembly along the helical axis (horizontal direction), sequence-programmed tenon
      and mortise were introduced to promote selective connections via pi-stacking
      interaction, sequence-complementarity, and shape-complementarity. For 2D self
      assembly along the helical side (vertical direction), the jigsaw shape
      complementarity in the top and bottom edges and the sequence-complementarity of
      single-stranded overhangs were used. We designed and prepared nine different
      jigsaw pieces and tried to obtain a 3 * 3 assembly. The proof of concept was
      obtained by performing the assembly in four different ways. Among them, the
      stepwise self-assembly from the three vertical trimer assemblies gave the target
      2D assembly with ~35% yield. Finally, the surfaces of jigsaw pieces were
      decorated with hairpin DNAs to display the letters of the alphabet, and the self
      assembled 2D structure displayed the word "DNA JIG SAW" in nanoscale. The method
      can be expanded to create self-assembled modules carrying various functional
      molecules for practical applications.

PMID- 21188997
TI  - Basic sites on periodic mesoporous organosilicas investigated by XPS and in situ
      FTIR of adsorbed pyrrole.
AB  - Oxygen sites in ethane-bridged and phenylene-bridged PMOs prepared using neutral
      templates in acidic conditions are characterized by means of XPS and FTIR
      spectroscopy of adsorbed pyrrole. Their electron donor ability is observed to be
      stronger than that of oxygens in pure amorphous silica of MCM-41 type and
      comparable to that reported for oxygen atoms in some alkali metal exchange
      zeolites. For pyrrole adsorbed on PMOs double interactions most probably occur,
      involving both silanols and electron donor sites at the surface. In the case of
      phenylene-bridged PMO preferential electron donor sites for interaction with
      pyrrole N-H group are aromatic rings rather than oxygens, as previously observed
      for adsorbed iodine.

PMID- 21188998
TI  - Patterning the tips of optical fibers with metallic nanostructures using
      nanoskiving.
AB  - Convenient and inexpensive methods to pattern the facets of optical fibers with
      metallic nanostructures would enable many applications. This communication
      reports a method to generate and transfer arrays of metallic nanostructures to
      the cleaved facets of optical fibers. The process relies on nanoskiving, in which
      an ultramicrotome, equipped with a diamond knife, sections epoxy nanostructures
      coated with thin metallic films and embedded in a block of epoxy. Sectioning
      produces arrays of nanostructures embedded in thin epoxy slabs, which can be
      transferred manually to the tips of optical fibers at a rate of approximately 2
      min(-1), with 88% yield. Etching the epoxy matrices leaves arrays of
      nanostructures supported directly by the facets of the optical fibers. Examples
      of structures transferred include gold crescents, rings, high-aspect-ratio
      concentric cylinders, and gratings of parallel nanowires.

PMID- 21188999
TI  - Landomycins P-W, cytotoxic angucyclines from Streptomyces cyanogenus S-136.
AB  - Streptomyces cyanogenus S-136 is the producer of previously reported landomycins
      A-D. An analysis of minor products of the strain led to isolation and structure
      elucidation of eight new congeners, named landomycins P-W (5, 6, 3, 17, 9, 10,
      15, 7), along with 10 other known angucyclin(on)es. The structures of the new
      compounds were established from their NMR and mass spectrometry data. The
      activity of these angucyclin(on)es was determined using MCF-7 (estrogen
      responsive) and MDA-231 (estrogen refractory) breast cancer cell lines. Cell
      viability assays showed that anhydrolandomycinone (2), landomycinone (11), and
      landomycin A (16) showed the best combined activities in both MCF-7 and MDA-231
      assays, with 2 being the most potent in the former and 11 and 16 in the latter.
      These data reveal that some of the aglycones are equipotent to the principle
      product 16, which contains the longest saccharide chain. Specifically,
      anhydrolandomycinone (2) was the most active against MCF-7 cells (IC(50) = 1.8
      MUM). Compounds with shorter saccharidal moieties were less potent against MCF-7.
      The fact that the most active landomycins have either long penta- or
      hexasaccharide chains or no sugars at all suggests that the large compounds may
      act by a different mode of action than their small sugar-free congeners. The
      results presented here provide more insights into the structure-activity
      relationship of landomycins.

PMID- 21189000
TI  - Highly sensitive and rapid detection of microcystin-LR in source and finished
      water samples using cantilever sensors.
AB  - Microcystin-leucine-arginine (MCLR) is one of the toxic microcystin congeners
      produced by the common cyanobacteria, blue-green algae. A piezoelectric-excited
      millimeter-sized cantilever (PEMC) sensor was developed for the sensitive
      detection of MCLR in a flow format using both monoclonal and polyclonal
      antibodies that bind specifically to MCLR. PEMC is a resonant cantilever sensor
      whose resonant frequency decreases as target analyte binds to its surface.
      Monoclonal antibody against MCLR was immobilized on the sensor surface via amine
      coupling. As the toxin in the sample water bound to the antibody, resonant
      frequency decreased proportional to toxin concentration. Three water matrices,
      namely buffer, tap water, and river water, were spiked with MCLR standards and
      were successfully detected in the dynamic range of 1 pg/mL to 100 ng/mL
      (effective concentration -250 fg/mL to 25 ng/mL). The sensor response was
      characterized by a log-linear relationship between resonant frequency change and
      MCLR concentration. Positive verification of MCLR detection was confirmed by a
      sandwich binding on the sensor with a second antibody binding to MCLR on the
      sensor (attached in first detection step) which caused a further resonant
      frequency decrease. We show for the first time that MCLR in various water samples
      can be detected at 1 pg/mL.

PMID- 21189001
TI  - Ultrasmall gold-doxorubicin conjugates rapidly kill apoptosis-resistant cancer
      cells.
AB  - Ultrasmall (mean diameter, 2.7 nm) gold nanoparticles conjugated to doxorubicin
      (Au-Dox) are up to 20-fold more cytotoxic to B16 melanoma cells than the
      equivalent concentration of doxorubicin alone, and act up to six times more
      quickly. Ultrasmall Au-Dox enters the cell endocytic vesicles and is also seen
      free in the cytoplasm and nuclei. This is in distinct contrast to larger
      particles reported in previous studies, which are excluded from the nucleus and
      which show no increased toxicity over Dox alone. Cell death with Au-Dox is
      confirmed to be apoptotic by TUNEL staining and ultrastructural examination using
      transmission electron microscopy. To further explore the mechanism of action, two
      other cell lines were examined: HeLa cells which are highly sensitive to Dox, and
      HeLa cells overexpressing Bcl-2 which show impaired apoptosis and Dox resistance.
      Interestingly, the Dox-sensitive cells show a slightly decreased sensitivity to
      Au-Dox relative to Dox alone, whereas the Dox-resistant cells are not resistant
      to Au-Dox. These results have implications for the design of chemotherapeutic
      nanoparticles, suggesting that it is possible to selectively target apoptosis
      resistant cancer cells while at the same time reducing cytotoxicity to normal
      cells.

PMID- 21189002
TI  - A method for determining small anharmonicity values from 2DIR spectra using
      thermally induced shifts of frequencies of high-frequency modes.
AB  - The off-diagonal anharmonicity for a pair of vibrational modes, determined as a
      shift of their combination level, Delta(12), can be linked to the molecular
      structure via modeling. The anharmonicity, Delta(12), also determines the
      amplitude and shape of the cross-peak between modes 1 and 2 measured using 2DIR
      spectroscopy. For large anharmonicities, the anharmonicity value can be readily
      obtained from the shape of the cross peak. In practice, however, the
      anharmonicities are often small (?1 cm(-1)). In this case, the amplitude of the
      cross peak rather than its shape is sensitive to the anharmonicity value, and
      determination of the anharmonicity requires absolute cross-peak measurements. We
      proposed and tested a new approach of determining anharmonicities, which is based
      on sensitivity of high-frequency vibrational modes to temperature. The approach
      permits calibrating the cross-peak amplitude in terms of the effective
      anharmonicity resulting from the thermal excitation of lower-frequency
      vibrational modes. It relies on a series of relative 2DIR measurements. While the
      sensitivity of the method depends on various specific parameters of the molecular
      system, such as transition dipoles and temperature sensitivity of the high
      frequency modes involved, we have estimated that the anharmonicities as small as
      0.02 cm(-1) can be determined for the cross peaks between -N(3) and C?O
      stretching modes using this approach.

PMID- 21189003
TI  - Hierarchically ordered macro-mesoporous TiO2-graphene composite films: improved
      mass transfer, reduced charge recombination, and their enhanced photocatalytic
      activities.
AB  - Hierarchically ordered macro-mesoporous titania films have been produced through
      a confinement self-assembly method within the regular voids of a colloidal
      crystal with three-dimensional periodicity. Furthermore, graphene as an excellent
      electron-accepting and electron-transporting material has been incorporated into
      the hierarchically ordered macro-mesoporous titania frameworks by in situ
      reduction of graphene oxide added in the self-assembly system. Incorporation of
      interconnected macropores in mesoporous films improves the mass transport through
      the film, reduces the length of the mesopore channel, and increases the
      accessible surface area of the thin film, whereas the introduction of graphene
      effectively suppresses the charge recombination. Therefore, the significant
      enhancement of photocatalytic activity for degrading the methyl blue has been
      achieved. The apparent rate constants for macro-mesoporous titania films without
      and with graphene are up to 0.045 and 0.071 min(-1), respectively, almost 11 and
      17 times higher than that for pure mesoporous titania films (0.0041 min(-1)).

PMID- 21189004
TI  - pH-dependent optical properties of a poly(phenylene ethynylene) conjugated
      polyampholyte.
AB  - A poly(phenylene ethynylene) conjugated polymer (PPE-NMe(3)(+)-COO(-)) containing
      tetraalkylammonium groups and carboxylate groups has been synthesized by
      Sonogashira coupling. Due to the presence of the strong cationic and weak anionic
      pendant units, the polymer undergoes a pH-induced transition from cationic
      polyelectrolyte to polyampholyte due to deprotonation of the carboxylic acid
      units in basic solution. Studies of the pH dependence of the polymers' optical
      properties reveal changes in absorption oscillator strength and fluorescence
      quantum efficiency that are triggered by the transition from cationic
      polyelectrolyte to polyampholyte nature. Stern-Volmer fluorescence quenching of
      PPE-NMe(3)(+)-COO(-) with a negatively charged quencher 1,4,5,8
      naphthalenediimide-N,N-bis(methylsulfonate) (NDS) shows that the polymer
      fluorescence quenching is amplified at low pH where the polymer is a polycation,
      whereas the quenching efficiency is considerably less at high pH.

PMID- 21189005
TI  - Experimental and theoretical examination of surface energy and adhesion of
      nitrifying and heterotrophic bacteria using self-assembled monolayers.
AB  - Biofilm-based systems, including integrated fixed-film activated sludge and
      moving bed bioreactors, are becoming increasingly popular for wastewater
      treatment, often with the goal of improving nitrification through the enrichment
      of ammonia and nitrite oxidizing bacteria. We have previously demonstrated the
      utility of self-assembled monolayers (SAMs) as tools for studying the initial
      attachment of bacteria to substrata systematically varying in physicochemical
      properties. In this work, we expanded these studies to bacteria of importance in
      wastewater treatment systems and we demonstrated attachment rates were better
      correlated with surface energy than with wettability (water contact angle).
      Toward the long-term goal of improving wastewater treatment performance through
      the strategic design of attachment substrata, the attachment rates of two
      autotrophic ammonia-oxidizing bacteria (Nitrosomonas europaea and Nitrosospira
      multiformis) and a heterotroph (Escherichia coli) were evaluated using SAMs with
      a range of wettabilities, surface energies, and functional properties (methyl,
      hydroxyl, carboxyl, trimethylamine, and amine terminated). Cell attachment rates
      were somewhat correlated with the water contact angles of the SAMs with polar
      terminal groups (hydroxyl, carboxyl, trimethylamine, and amine). Including all
      SAM surfaces, a better correlation was found for all bacteria between attachment
      rates and surface free energy, as determined using the Lewis Acid-Base approach.
      The ammonia-oxidizers had higher adhesion rates on the SAMs with higher surface
      energies than did the heterotroph. This work demonstrated the successful
      application of SAMs to determine the attachment surface preferences of bacteria
      important to wastewater treatment, and it provides guidance for a new area of
      research aimed at improving treatment performance through rational attachment
      surface design.

PMID- 21189006
TI  - Hydrogen bonding in the hexagonal ice surface.
AB  - A recently developed technique in sum frequency generation spectroscopy,
      polarization angle null (or PAN-SFG), is applied to two orientations of the prism
      face of hexagonal ice. It is found that the vibrational modes of the surface are
      similar in different faces. As in the basal face, the prism face of ice contains
      five dominant resonances: 3096, 3146, 3205, 3253, and 3386 cm(-1). On the basal
      face, the reddest resonance occurs at 3098 cm(-1); within the bandwidth, the same
      as the prism face. On both the prism and basal faces, this mode contains a
      significant quadrupole component and is assigned to the bilayer stitching
      hydrogen bonds. The bluest of the resonances, 3386 cm(-1), occurs slightly blue
      shifted at 3393 cm(-1) in the basal face. The prism face has two orientations:
      one with the optic or c axis in the input plane (the plane formed by the surface
      normal and the interrogating beam propagation) and one with the c axis
      perpendicular to the input plane. The 3386 cm(-1) mode has significant intensity
      only with the c axis in the input plane. On the basis of these orientation
      characteristics, the 3386 cm(-1) mode is assigned to double-donor molecules in
      either the top half bilayer or in the lower half bilayer. On the basis of
      frequency considerations, it is assigned to double-donor molecules in the top
      half bilayer. These are water molecules containing a nonbonded lone pair. In
      addition to identification of the components of the broad hydrogen-bonded region,
      PAN-SFG measures the tangential vs longitudinal content of the vibrational modes.
      In accord with previous suggestions, the lower frequency modes are predominantly
      tangential, whereas the higher frequency modes are mainly longitudinal. On the
      prism face, the 3386 cm(-1) mode is entirely longitudinal.

PMID- 21189007
TI  - Metal-molecule Schottky junction effects in surface enhanced Raman scattering.
AB  - We propose a complementary interpretation of the mechanism responsible for the
      strong enhancement observed in surface enhanced raman scattering (SERS). The
      effect of a strong static local electric field due to the Schottky barrier at the
      metal-molecule junction on SERS is systematically investigated. The study
      provides a viable explanation to the low repeatability of SERS experiments as
      well as the Raman peak shifts as observed in SERS and raw Raman spectra. It was
      found that a strong electrostatic built-in field at the metal-molecule junction
      along specific orientations can result in 2-4 more orders of enhancement in SERS.

PMID- 21189008
TI  - Poly(L-lysine)-mediated biomimetic silica synthesis: effects of mixing sequences
      and counterion concentrations.
AB  - Two poly(L-lysine.HBr) (PLL) homopolypeptides along with phosphate buffer were
      used as organic templates to direct biomimetic silica synthesis under ambient
      conditions. We found that mixing sequence of reaction species played a key role
      in terms of controlling resulting silica morphologies. Premixing PLL solution
      with phosphate buffer followed with addition of silicic acid produced regular
      hexagonal silica plates, while premixing silicic acid with either PLL or
      phosphate solution prior to adding phosphate buffer or PLL solution only produced
      irregular silica nanoparticles. In addition, we found that the concentration of
      phosphate ions was also an important factor to control silica structures. When
      the ratio of phosphate/lysine residue (delta) was smaller than one, PLL only
      produced irregular silica particles. When delta was larger than 2.5, PLL produced
      regular silica plates. We performed CD measurements to track the conformation
      transition of PLL during biomineralization process and found that the resulting
      silica structures were closely related to the secondary structure of PLL
      regardless of experimental conditions. Only when PLL underwent an in situ coil
      helix transition could ordered silica structures be produced.

PMID- 21189009
TI  - CO2 mitigation via capture and chemical conversion in seawater.
AB  - A lab-scale seawater/mineral carbonate gas scrubber was found to remove up to 97%
      of CO(2) in a simulated flue gas stream at ambient temperature and pressure, with
      a large fraction of this carbon ultimately converted to dissolved calcium
      bicarbonate. After full equilibration with air, up to 85% of the captured carbon
      was retained in solution, that is, it did not degas or precipitate. Thus, above
      ground CO(2) hydration and mineral carbonate scrubbing may provide a relatively
      simple point-source CO(2) capture and storage scheme at coastal locations. Such
      low-tech CO(2) mitigation could be especially relevant for retrofitting to
      existing power plants and for deployment in the developing world, the primary
      source of future CO(2) emissions. Addition of the resulting alkaline solution to
      the ocean may benefit marine ecosystems that are currently threatened by
      acidification, while also allowing the utilization of the vast potential of the
      sea to safely sequester anthropogenic carbon. This approach in essence hastens
      Nature's own very effective but slow CO(2) mitigation process; carbonate mineral
      weathering is a major consumer of excess atmospheric CO(2) and ocean acidity on
      geologic times scales.

PMID- 21189010
TI  - Ultrafast geminate recombination after photodetachment of aqueous hydroxide.
AB  - The photodetachment of aqueous hydroxide (OH(-)(aq) and OD(-)(aq)) is studied
      using femtosecond pump-probe and pump-repump-probe spectroscopy. The electron is
      detached after excitation of the hydroxide ion to a charge-transfer-to-solvent
      (CTTS) state at 202 nm. An early intermediate is observed that builds up within
      160 fs and is assigned to nonequilibrated OH-electron pairs. The subsequent
      dynamics are governed by thermalization, partial recombination, and dissociation
      of the pairs, yielding the final hydrated electrons and hydroxyl radicals. An
      additional pulse at 810 nm is used for secondary excitation of the intermediate
      species so that more insight is gained into the recombination process(es). Using
      this technique we observe a novel geminate recombination channel of OH with
      adjacent hydrated electrons. This channel leads to ultrafast quenching (700 fs)
      of almost half the initial number of radicals. The fast mechanism displays an
      isotope effect of 1.4 (for OD(-)(aq) quantum yield 35%, time constant 1.0 ps).
      This process was not observed in similar experiments on aqueous bromide and seems
      to be related to the special properties of the hydroxide ion and its local H
      bonding environment. Our findings underline the high reactivity of the
      prehydrated electron.

PMID- 21189012
TI  - Diurnal variability of pharmaceutical, personal care product, estrogen and
      alkylphenol concentrations in effluent from a tertiary wastewater treatment
      facility.
AB  - Hourly samples of tertiary wastewater effluent were analyzed for 30
      pharmaceuticals, personal care products, estrogenic steroids, and alkylphenols in
      order to better understand the rate at which these compounds enter the
      environment. Several distinct patterns of daily cycling were observed, and were
      characterized as three separate categories. The concentrations of compounds such
      as trimethoprim, sulfamethoxazole, naproxen, estrone, and triclosan varied
      greatly during a daily cycle, with relative standard deviations exceeding 100% of
      their daily mean. Less extreme daily cycles were seen for other compounds such as
      azithromycin, atenolol, tert-octylphenol, iopromide and gemfibrozil. Peak
      concentrations for most compounds occurred in the early evening (5-8 pm).
      However, some compounds including carbamazepine, primidone, fluoxetine, and
      triclocarban exhibited little or no variability.

PMID- 21189013
TI  - Effects of thermal and high hydrostatic pressure processing and storage on the
      content of polyphenols and some quality attributes of fruit smoothies.
AB  - The aim of the present study was the evaluation of high hydrostatic pressure
      (HHP) processing on the levels of polyphenolic compounds and selected quality
      attributes of fruit smoothies compared to fresh and mild conventional
      pasteurization processing. Fruit smoothie samples were thermally (P(70) > 10 min)
      or HHP processed (450 MPa/1, 3, or 5 min/20  degrees C) (HHP1, HHP3, and HHP5,
      respectively). The polyphenolic content, color difference (DeltaE), sensory
      acceptability, and rheological (G'; G''; G*) properties of the smoothies were
      assessed over a storage period of 30 days at 4  degrees C. Processing had a
      significant effect (p < 0.001) on the levels of polyphenolic compounds in
      smoothies. However, this effect was not consistent for all compound types. HHP
      processed samples (HHP1 and HHP3) had higher (p < 0.001) levels of phenolic
      compounds, for example, procyanidin B1 and hesperidin, than HHP5 samples. Levels
      of flavanones and hydroxycinnamic acid compounds decreased (p < 0.001) after 30
      days of storage at 2-4  degrees C). Decreases were particularly notable between
      days 10 and 20 (hesperidin) and days 20 and 30 (chlorogenic acid) (p < 0.001).
      There was a wide variation in DeltaE values recorded over the 30 day storage
      period (p < 0.001), with fresh and thermally processed smoothies exhibiting lower
      color change than their HHP counterparts (p < 0.001). No effect was observed for
      the type of process on complex modulus (G*) data, but all smoothies became less
      rigid during the storage period (p < 0.001). Despite minor product deterioration
      during storage (p < 0.001), sensory acceptability scores showed no preference for
      either fresh or processed (thermal/HHP) smoothies, which were deemed acceptable
      (>3) by panelists.

PMID- 21189014
TI  - Physical and sensory properties of all-barley and all-oat breads with additional
      hydroxypropyl methylcellulose (HPMC) beta-glucan.
AB  - Hydroxypropyl methylcellulose (HPMC) is a substituted cellulose that reduces
      serum cholesterol at modest intake levels. HPMC has also been used for decades in
      gluten-free breads at a level to optimize loaf volume. Because consumers resist
      the consumption of whole wheat breads, the sensory and physical properties of all
      oat and barley breads incorporating HPMC were evaluated. Oat and barley also
      contain beta-glucan, a glucose polymer similar to HPMC that also lowers
      cholesterol. The textural and sensory properties of the breads were determined by
      instrumental and chemical methods and sensory panels. HPMC increased the loaf
      volume of the breads by up to 2 times and decreased hardness immediately after
      baking and after up to 3 days of storage. Barley bread with HPMC was rated the
      highest in overall acceptability by sensory panelists compared to oat and wheat
      breads with or without HPMC.

PMID- 21189015
TI  - Alkyl and other major structures in (13)C-labeled glucose-glycine melanoidins
      identified by solid-state nuclear magnetic resonance.
AB  - The high molecular weight fraction of melanoidins formed in the Maillard reaction
      between isotopically labeled glucose and glycine has been characterized
      comprehensively using advanced (13)C and (15)N solid-state NMR with spectral
      editing. We have focused on the fate of glucose in a 1:1 molar ratio with
      glycine, heated as a coprecipitated powder at 125  degrees C for 2 h.
      Quantitative (13)C NMR spectra show that aromatic and alkene carbons make up only
      40% of the total in the melanoidin. Spectra of melanoidins made from specifically
      labeled ((13)C1, (13)C2, (13)C3, and (13)C6) glucose are strikingly different,
      proving that specific structures of various types are formed. More than half of
      the glucose-C1 carbons form new C-C bonds, not just C-O and C-N bonds. Most C2
      carbons are bonded to N or O and not protonated, while C3 shows the reverse
      trends. C4 and C5 remain significantly in alkyl OCH sites or become part of
      heterocyclic aromatic rings. C6 undergoes the least transformation, remaining
      half in OCH(2) groups. Functional groups characteristic of fragmentation are
      relatively insignificant, except for N/O-C2 ? O groups indicating some C(1) +
      C(5) and C(2) + C(4) fragmentation. On the basis of (13)C-(13)C and (15)N-(13)C
      correlation spectra, 11 "monomer units" have been identified, including several
      types of alkyl chain or ring segments, furans, pyrroles, imidazoles, and
      oxazoles; these are mixed on the nanometer scale. This complexity explains why
      simple models cannot represent the structure of melanoidins. While none of the
      "monomer units" represents more than 15% of all C, the 11 units identified
      together account for more than half of all glucose carbon in the melanoidin.

PMID- 21189016
TI  - The formation of wine lactone from grape-derived secondary metabolites.
AB  - Wine lactone (i.e., 3a,4,5,7a-tetrahydro-3,6-dimethylbenzofuran-2(3H)-one, 1a/1b)
      was formed hydrolytically at wine pH from both racemic (E)-2,6-dimethyl-6
      hydroxyocta-2,7-dienoic acid (3) and the corresponding glucose ester 2a at 45 
      degrees C but at room temperature was only formed from the acid 3. The glucose
      ester does not appear to be a significant precursor for the formation of wine
      lactone in wine. The slow formation of wine lactone from the free acid 3
      indicates that the acid is not likely to be an important precursor to wine
      lactone in young wines unless present in high concentration (? 1 mg/L), but could
      be a significant precursor to wine lactone in wine that is several years old. The
      wine lactone formed in hydrolysates of the (6R)-enantiomer of 3 was partially
      enriched in the (3S,3aS,7aR)-enantiomer 1a when the hydrolysis was conducted at
      pH 3.2 and 100  degrees C in a closed vessel or under simultaneous distillation
      extraction (SDE) conditions, and the enantiomeric excess (ee) varied from 5 to
      22%. Hydrolysis of (6R)-3 in sealed ampules at 45  degrees C and at pH 3.0, 3.2,
      or 3.4 gave near-racemic wine lactone, but when the hydrolyses were conducted at
      room temperature, the product was enriched in the (3S,3aS,7aR)-enantiomer 1a and
      the ee was greater at higher pH (up to 60% at pH 3.4).

PMID- 21189017
TI  - Roles of grape thaumatin-like protein and chitinase in white wine haze formation.
AB  - Grape chitinase was found to be the primary cause of heat-induced haze formation
      in white wines. Chitinase was the dominant protein in a haze induced by treating
      Sauvignon blanc wine at 30  degrees C for 22 h. In artificial wines and real
      wines, chitinase concentration was directly correlated to the turbidity of heat
      induced haze formation (50  degrees C for 3 h). Sulfate was confirmed to have a
      role in haze formation, likely by converting soluble aggregates into larger
      visible haze particles. Thaumatin-like protein was detected in the insoluble
      fraction by SDS-PAGE analysis but had no measurable impact on turbidity.
      Differential scanning calorimetry demonstrated that the complex mixture of
      molecules in wine plays a role in thermal instability of wine proteins and
      contributes additional complexity to the wine haze phenomenon.

PMID- 21189018
TI  - Stabilization of the heavy methylene analogues, GeH2 and SnH2, within the
      coordination sphere of a transition metal.
AB  - The heavy group 14 methylene analogues, EH2, (E = Ge and Sn) have been stabilized
      via efficient methods, thus enabling the chemistry of these novel inorganic
      hydrides to be explored in depth.

PMID- 21189020
TI  - New drug-like hydroxyphenylnaphthol steroidomimetics as potent and selective
      17beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of
      estrogen-dependent diseases.
AB  - Inhibition of 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) is a novel
      and attractive approach to reduce the local levels of the active estrogen 17beta
      estradiol in patients with estrogen-dependent diseases like breast cancer or
      endometriosis. With the aim of optimizing the biological profile of 17beta-HSD1
      inhibitors from the hydroxyphenylnaphthol class, structural optimizations were
      performed at the 1-position of the naphthalene by introduction of different
      heteroaromatic rings as well as substituted phenyl groups. In the latter class of
      compounds, which were synthesized applying Suzuki-cross coupling, the 3
      methanesulfonamide 15 turned out to be a highly potent 17beta-HSD1 inhibitor
      (IC(50) = 15 nM in a cell-free assay). It was also very active in the cellular
      assay (T47D cells, IC(50) = 71 nM) and selective toward 17beta-HSD2 and the
      estrogen receptors alpha and beta. It showed a good membrane permeation and
      metabolic stability and was orally available in the rat.

PMID- 21189019
TI  - Identifying chelators for metalloprotein inhibitors using a fragment-based
      approach.
AB  - Fragment-based lead design (FBLD) has been used to identify new metal-binding
      groups for metalloenzyme inhibitors. When screened at 1 mM, a chelator fragment
      library (CFL-1.1) of 96 compounds produced hit rates ranging from 29% to 43% for
      five matrix metalloproteases (MMPs), 24% for anthrax lethal factor (LF), 49% for
      5-lipoxygenase (5-LO), and 60% for tyrosinase (TY). The ligand efficiencies (LE)
      of the fragment hits are excellent, in the range of 0.4-0.8 kcal/mol. The MMP
      enzymes all generally elicit the same chelators as hits from CFL-1.1; however,
      the chelator fragments that inhibit structurally unrelated metalloenzymes (LF, 5
      LO, TY) vary considerably. To develop more advanced hits, one hit from CFL-1.1, 8
      hydroxyquinoline, was elaborated at four different positions around the ring
      system to generate new fragments. 8-Hydroxyquinoline fragments substituted at
      either the 5- or 7-positions gave potent hits against MMP-2, with IC(50) values
      in the low micromolar range. The 8-hydroxyquinoline represents a promising new
      chelator scaffold for the development of MMP inhibitors that was discovered by
      use of a metalloprotein-focused chelator fragment library.

PMID- 21189021
TI  - Detailed biophysical characterization of the acid-induced PrP(c) to PrP(beta)
      conversion process.
AB  - Prions are believed to spontaneously convert from a native, monomeric highly
      helical form (called PrP(c)) to a largely beta-sheet-rich, multimeric and
      insoluble aggregate (called PrP(sc)). Because of its large size and insolubility,
      biophysical characterization of PrP(sc) has been difficult, and there are several
      contradictory or incomplete models of the PrP(sc) structure. A beta-sheet-rich,
      soluble intermediate, called PrP(beta), exhibits many of the same features as
      PrP(sc) and can be generated using a combination of low pH and/or mild denaturing
      conditions. Studies of the PrP(c) to PrP(beta) conversion process and of
      PrP(beta) folding intermediates may provide insights into the structure of
      PrP(sc). Using a truncated, recombinant version of Syrian hamster PrP(beta)
      (shPrP(90-232)), we used NMR spectroscopy, in combination with other biophysical
      techniques (circular dichroism, dynamic light scattering, electron microscopy,
      fluorescence spectroscopy, mass spectrometry, and proteinase K digestion), to
      characterize the pH-driven PrP(c) to PrP(beta) conversion process in detail. Our
      results show that below pH 2.8 the protein oligomerizes and conversion to the
      beta-rich structure is initiated. At pH 1.7 and above, the oligomeric protein can
      recover its native monomeric state through dialysis to pH 5.2. However, when
      conversion is completed at pH 1.0, the large oligomer "locks down" irreversibly
      into a stable, beta-rich form. At pH values above 3.0, the protein is amenable to
      NMR investigation. Chemical shift perturbations, NOE, amide line width, and T(2)
      measurements implicate the putative "amylome motif" region, "NNQNNF" as the
      region most involved in the initial helix-to-beta conversion phase. We also found
      that acid-induced PrP(beta) oligomers could be converted to fibrils without the
      use of chaotropic denaturants. The latter finding represents one of the first
      examples wherein physiologically accessible conditions (i.e., only low pH) were
      used to achieve PrP conversion and fibril formation.

PMID- 21189022
TI  - Single-walled carbon nanotube thermopile for broadband light detection.
AB  - We designed a thermopile based on a PN doping profile engineered in a suspended
      film of single-walled carbon nanotubes (SWNTs). Using estimates of the film local
      Seebeck coefficients, the SWNT thermopile was optimized in situ through
      depositions of potassium dopants. The overall performances of the thermopile were
      found to be comparable to state-of-the-art SWNT bolometers. The device is
      characterized at room temperature by a time response of 36 ms, typical of thermal
      detectors, and an optimum spectral detectivity of 2 * 10(6) cm Hz(1/2)/W in the
      visible and near-infrared. This paper presents the first thermopile made of a
      suspended SWNT film and paves the way to new applications such as broadband light
      (including THz) detection and thermoelectric power generation.

PMID- 21189023
TI  - Synthesis and molecular modeling of novel tetrahydro-beta-carboline derivatives
      with phosphodiesterase 5 inhibitory and anticancer properties.
AB  - New derivatives based upon the tetrahydro-beta-carboline-hydantoin and tetrahydro
      beta-carboline-piperazinedione scaffolds were synthesized. All compounds were
      evaluated for their ability to inhibit PDE5 in vitro, and numerous compounds with
      IC(50) values in the low nanomolar range were identified including compounds
      derived from l-tryptophan. Compounds with high potency versus PDE5 were then
      evaluated for inhibitory activity against other PDEs to assess isozyme
      selectivity. Compound 5R,11aS-5-(3,4-dichlorophenyl)-2-ethyl-5,6,11,11a
      tetrahydro-1H-imidazo[1',5':1,6]pyrido[3,4-b]indole-1,3(2H)dione 14 showed a
      selectivity index of >200 for cGMP hydrolysis by PDE5 versus PDE11. Meanwhile,
      6R,12aR-6-(2,4-dichlorophenyl)-2-ethyl-2,3,6,7,12,12a
      hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4dione 45 demonstrated strong
      potency for inhibition of PDE11 with an IC(50) value of 11 nM, representing the
      most potent PDE11 inhibitor thus far reported. Docking experiments differentiated
      between active and inactive analogues and revealing the conformational, steric,
      and lipophilic necessities for potent PDE5 inhibition. Many derivatives,
      including potent PDE5 inhibitors, were able to inhibit the growth of the MDA-MB
      231 breast tumor cell line with low micromolar potency.

PMID- 21189024
TI  - Polarization-angle-scanning 2DIR spectroscopy of coupled anharmonic oscillators:
      a polarization null angle method.
AB  - Two-dimensional (2D) optical spectroscopy based on stimulated photon echo
      geometry requires multiple ultrashort pulses of which spatiotemporal properties
      and optical phases can be precisely controlled. Also, it is possible to change
      the incident beam polarization directions defined in a laboratory frame. Here, we
      introduce the polarization-angle-scanning (PAS) 2D spectroscopy and show that the
      diagonal and cross-peak amplitudes in the 2D spectrum can be arbitrarily
      modulated by spatially controlling the beam polarization directions. For a
      coupled anharmonic oscillator system, we specifically demonstrate that either
      diagonal or cross-peaks in the measured 2DIR spectra can be selectively
      eliminated and show that such polarization angles provide direct information on
      the relative angles between coupled transition dipoles and thereby on intricate
      details of molecular structures. We thus anticipate that the present PAS 2D
      optical spectroscopy can be a useful experimental method enabling us to probe
      structural evolutions of nonequilibrium state molecules by monitoring the time
      dependent changes of the relative transition dipole directions.

PMID- 21189025
TI  - Three-dimensional hierarchical composite scaffolds consisting of
      polycaprolactone, beta-tricalcium phosphate, and collagen nanofibers:
      fabrication, physical properties, and in vitro cell activity for bone tissue
      regeneration.
AB  - beta-Tricalcium phosphate (beta-TCP) and collagen have been widely used to
      regenerate various hard tissues, but although Bioceramics and collagen have
      various biological advantages with respect to cellular activity, their usage has
      been limited due to beta-TCP's inherent brittleness and low mechanical
      properties, along with the low shape-ability of the three-dimensional collagen.
      To overcome these material deficiencies, we fabricated a new hierarchical
      scaffold that consisted of a melt-plotted polycaprolactone (PCL)/beta-TCP
      composite and embedded collagen nanofibers. The fabrication process was combined
      with general melt-plotting methods and electrospinning. To evaluate the
      capability of this hierarchical scaffold to act as a biomaterial for bone tissue
      regeneration, physical and biological assessments were performed. Scanning
      electron microscope (SEM) micrographs of the fabricated scaffolds indicated that
      the beta-TCP particles were uniformly embedded in PCL struts and that electrospun
      collagen nanofibers (diameter = 160 nm) were well layered between the composite
      struts. By accommodating the beta-TCP and collagen nanofibers, the hierarchical
      composite scaffolds showed dramatic water-absorption ability (100% increase),
      increased hydrophilic properties (20%), and good mechanical properties similar to
      PCL/beta-TCP composite. MTT assay and SEM images of cell-seeded scaffolds showed
      that the initial attachment of osteoblast-like cells (MG63) in the hierarchical
      scaffold was 2.2 times higher than that on the PCL/beta-TCP composite scaffold.
      Additionally, the proliferation rate of the cells was about two times higher than
      that of the composite scaffold after 7 days of cell culture. Based on these
      results, we conclude that the collagen nanofibers and beta-TCP particles in the
      scaffold provide good synergistic effects for cell activity.

PMID- 21189026
TI  - Coordination polymers of zinc with (eta6-benzenecarboxylate) chromium
      tricarbonyl.
AB  - Different coordination polymers were obtained by the reaction of (benzoic acid)
      chromium tricarbonyl with zinc acetate in the presence of various organic
      dipyridyl linkers. Depending on the nature of the linker either monomeric or
      polymeric compounds were obtained. Reactions of (benzoic acid) chromium
      tricarbonyl with zinc acetate and bidentate pyridine based ligands 4,4'
      bipyridine (4,4'-bipy), 1,2-bis(4-pyridyl)ethane (bpe), 1,3-bis(4-pyridyl)propane
      (tmdp), and 2,2'dipyridylamine (DPA) afforded the novel coordination polymers
      [Zn[{eta(6)-C(6)H(5)COO}Cr(CO)(3)](2)(4,4'-bipy)](n), [Zn[{eta(6)
      C(6)H(5)COO}Cr(CO)(3)](2)(bpe)](n), [Zn[{eta(6)
      C(6)H(5)COO}Cr(CO)(3)](2)(tmdp)}](n), and the monomeric complex [Zn[{eta(6)
      C(6)H(5)COO}Cr(CO)(3)](2)(DPA)]. The solid state structures of all compounds were
      determined by single crystal X-ray diffraction. By using 1,3-bis(4
      pyridyl)propane as a linker a chiral infinite helical structure was formed in the
      solid state. Thermogravimetric analysis (TGA) studies showed that upon heating
      the carbonyl groups of the {eta(6)-C(6)H(5)COO}Cr(CO)(3) anion were lost before
      the organic ligand sphere was thermally decomposed.

PMID- 21189027
TI  - Effective extraction of photoluminescence from a diamond layer with a photonic
      crystal.
AB  - Diamond-based materials possess many unique properties, one of them being a broad
      band visible photoluminescence due to a variety of color centers. However, a high
      material refractive index makes the extraction of photoluminescence (PL) from a
      diamond layer inefficient. In this paper, we show that by periodical
      nanopatterning of the film's surface into a form of two-dimensional photonic
      crystal, the extraction of PL can be strongly enhanced within the whole visible
      spectrum compared to the extraction of PL in a pristine or randomly nanopatterned
      film. On the basis of theoretical calculations, enhancement is shown to be due to
      the photonic crystal effect, including efficient coupling of an excitation laser
      into the diamond.

PMID- 21189028
TI  - Flexible and metal-free light-emitting electrochemical cells based on graphene
      and PEDOT-PSS as the electrode materials.
AB  - We report flexible and metal-free light-emitting electrochemical cells (LECs)
      using exclusively solution-processed organic materials and illustrate interesting
      design opportunities offered by such conformable devices with transparent
      electrodes. Flexible LEC devices based on chemically derived graphene (CDG) as
      the cathode and poly(3,4-ethylenedioxythiophene) mixed with
      poly(styrenesulfonate) as the anode exhibit a low turn-on voltage for yellow
      light emission (V = 2.8 V) and a good efficiency 2.4 (4.0) cd/A at a brightness
      of 100 (50) cd/m(2). We also find that CDG is electrochemically inert over a wide
      potential range (+1.2 to -2.8 V vs ferrocene/ferrocenium) and exploit this
      property to demonstrate planar LEC devices with CDG as both the anode and the
      cathode.

PMID- 21189029
TI  - Surface-directed spinodal decomposition in poly[3-hexylthiophene] and C61-butyric
      acid methyl ester blends.
AB  - Demixed blends of poly[3-hexylthiophene] (P3HT) and C61-butyric acid methyl ester
      (PCBM) are widely used in photovoltaic diodes (PV) and show excellent quantum
      efficiency and charge collection properties. We find the empirically optimized
      literature process conditions give rise to demixing during solvent
      (chlorobenzene) evaporation by spinodal decomposition. Ultraviolet photoemission
      spectroscopy (UPS) and X-ray photoemission spectroscopy (XPS) results are
      consistent with the formation of 1-2 nm thick surface layers on both interfaces,
      which trigger the formation of surface-directed waves emanating from both film
      surfaces. This observation is evidence that spinodal demixing (leading to a
      bicontinuous phase morphology) precedes the crystallization of the two
      components. We propose a model for the interplay of demixing and crystallization
      which explains the broadly similar PV performance for devices made with the
      bottom electrodes either as hole or electron collector. The process regime of
      temporal separation of demixing and crystallization is attractive because it
      provides a way to control the morphology and thereby the efficiency of PV
      devices.

PMID- 21189030
TI  - Triplet excimer emission in a series of 4,4'-bis(N-carbazolyl)-2,2'-biphenyl
      derivatives.
AB  - Carbazole-based materials such as 4,4'-bis(N-carbazolyl)-2,2'-biphenyl (CBP) and
      its derivatives are frequently used as matrix materials for phosphorescent
      emitters in organic light emitting diodes (OLED)s. An essential requirement for
      such matrix materials is a high energy of their first triplet excited state. Here
      we present a detailed spectroscopic investigation supported by density functional
      theory (DFT) calculations on two series of CBP derivatives, where CH(3) and CF(3)
      substituents on the 2- and 2'-position of the biphenyl introduce strong torsion
      into the molecular structure. We find that the resulting poor coupling between
      the two halves of the molecules leads to an electronic structure similar to that
      of N-phenyl-3,6-dimethylcarbazole, with a high triplet-state energy of 2.95 eV.
      However, we also observe a triplet excimer emission centered at about 2.5-2.6 eV
      in all compounds. We associate this triplet excimer with a sandwich geometry of
      neighboring carbazole moieties. For compounds with the more polar CF(3)
      substituents, the lifetime of the intermolecular triplet excited state extends
      into the millisecond range for neat films at room temperature. We attribute this
      to an increased charge-transfer character of the intermolecular excited state for
      the more polar substituents.

PMID- 21189031
TI  - The different nature of band edge absorption and emission in colloidal PbSe/CdSe
      core/shell quantum dots.
AB  - We present a quantitative analysis of the absorption and luminescence of
      colloidal PbSe/CdSe core/shell quantum dots (QDs). In absorption, both the energy
      and the oscillator strength of the first exciton transition coincide with that of
      plain PbSe QDs. In contrast, luminescence lifetime measurements indicate that the
      oscillator strength of the emitting transition is reduced by at least a factor of
      4 compared to PbSe core QDs. Moreover, the addition of an electron scavenger
      quenches the PbSe/CdSe emission, while a hole scavenger does not. This implies
      that the electron wave function reaches the QD surface, while the hole is
      confined to the PbSe core. These observations are consistent with calculations
      based on the effective mass model, which show that PbSe/CdSe QDs are at the
      boundary between the type-I and quasi-type-II regime, where the electron spreads
      over the entire nanoparticle and the hole remains confined in the PbSe core.
      However, as this only leads to a minor reduction of the oscillator strength, it
      follows that the drastic reduction of the oscillator strength in emission cannot
      be explained in terms of electron delocalization. In combination with the
      increased Stokes shift for PbSe/CdSe QDs, this indicates that the emission
      results from lower energy states that are fundamentally different from the
      absorbing states.

PMID- 21189033
TI  - Atoms and bonds in molecules from radial densities.
AB  - Radial densities are explored as an alternative method for partitioning the
      molecular density into atomic regions and bonding regions. The radial densities
      for atoms in molecules are similar to those of an isolated atom. The method may
      also provide an alternative to Bragg-Slater radii.

PMID- 21189032
TI  - Chelating effect as a driving force for the selective formation of heteroligated
      Pt(II) complexes with bidentate phosphino-chalcoether ligands.
AB  - The halide-induced ligand rearrangement reaction (HILR) has been employed to
      provide selective and exclusive in situ formation of heteroligated Rh(I), Pd(II),
      and Pt(II) complexes with bidentate phosphino-chalcoether ligands. To gain
      insights on the nature of this unique reaction, we explored this process via the
      stepwise addition of bidentate phosphino-chalcoether (P, X; X = S or Se) and
      relevant monodentate phosphine ligands with a Pt(II) metal precursor. The
      corresponding monoligated complexes were obtained in quantitative yields by
      reacting 1 equiv of a P, X bidentate ligand with Pt(II) and were fully
      characterized via single crystal X-ray diffraction studies and heteronuclear
      ((31)P, (77)Se, and (195)Pt) NMR spectroscopy in solution. These species were
      further reacted with a second equivalent of either a bidentate ligand or the
      monodentate ethyl diphenylphosphine ligand, resulting in the clean formation of
      the heteroligated species or, in the case of the monodentate ligand with an
      electron-withdrawing bidentate ligand, a mixture of products. On the basis of
      competitive exchange reactions between these heteroligated, homoligated, and
      monoligated complexes, we conclude that ligand chelation plays a crucial role in
      the Pt(II) HILR. The in situ preferable formation of the stable monoligated
      complex allows for ligand sorting to occur in these systems. In all cases where
      the heteroligated product results, the driving force to these species is ligand
      chelation.

PMID- 21189034
TI  - Fe3O4 nanoparticle-supported copper(I) pybox catalyst: magnetically recoverable
      catalyst for enantioselective direct-addition of terminal alkynes to imines.
AB  - An Fe(3)O(4) nanoparticle-supported copper(I) pybox catalyst, which exhibits
      excellent reactivity and yields products with good enantioselectivity, was
      developed. As a proof of concept, six optically active propargyl amines were
      obtained in excellent yields. The catalyst can be magnetically removed and
      recycled easily six times without a decrease in activity or enantioselectivity.

PMID- 21189035
TI  - Aerosolized PLA and PLGA nanoparticles enhance humoral, mucosal and cytokine
      responses to hepatitis B vaccine.
AB  - Porous poly(L-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA)
      nanoparticles were tested for pulmonary delivery of hepatitis B vaccine. In
      particular, the effects of particle size and hydrophobicity on mucosal and cell
      mediated immune responses were investigated. Three formulations of PLA and PLGA
      nanoparticles containing a fixed amount of hepatitis B surface antigen (HBsAg)
      were prepared by a double-emulsion-solvent-evaporation method and characterized
      for surface morphology, charge, size, density and in vitro release. The immune
      responses were studied by measuring secretory IgA levels in mucosal fluids and
      quantitating cytokine levels in rat spleen homogenates. Particle uptake was
      studied in rat alveolar macrophages. Scanning electron microscopy revealed
      particles with smooth surfaces. Zeta potential measurements indicated that the
      particles carried negative surface charges. The antigen was continuously released
      for 42 days in phosphate buffer. Hydrophobic particles >500 nm elicited a more
      robust increase in secretary IgA, interleukin-2 and interferon-gamma levels
      compared to hydrophilic particles <500 nm. Large hydrophobic particles were more
      efficiently internalized by rat alveolar macrophages compared to smaller
      hydrophilic particles. Calu-3 cell viability studies indicate that the viability
      of cells is not affected by nanoparticulate formulations. This study demonstrates
      that inhalable nanoparticles of HBsAg produce an enhancement of immune responses.

PMID- 21189036
TI  - Adiabatic and non-adiabatic non-equilibrium stochastic dynamics of single
      regulating genes.
AB  - We explore the stochastic dynamics of self-regulative genes from fluctuations of
      molecular numbers and of on and off switching of gene states due to regulatory
      protein binding/unbinding to the genes. We found when the binding/unbinding is
      relatively fast (slow) compared with the synthesis/degradation of proteins in
      adiabatic (nonadiabatic) case the self-regulators can exhibit one or two peak
      (two peak) distributions in protein concentrations. This phenomena can also be
      quantified through Fano factors. This shows that even with the same architecture
      (topology of wiring) networks can have quite different functions (phenotypes),
      consistent with recent single molecule single gene experiments. We further found
      the inhibition and activation curves to be consistent with previous results
      (monomer binding) in adiabatic regime, but, in nonadiabatic regimes, show
      significantly different behaviors with previous predictions (monomer binding).
      Such difference is due to the slow (nonadiabatic) dimer binding/unbinding effect,
      and it has never been reported before. We derived the nonequilibrium phase
      diagrams of monostability and bistability in adiabatic and nonadiabatic regimes.
      We studied the dynamical trajectories of the self-regulating genes on the
      underlying landscapes from nonadiabatic to adiabatic limit, and we provide a
      global picture of understanding and show an analogy to the electron transfer
      problem. We studied the stability and robustness of the systems through mean
      first passage time (MFPT) from one peak (basin of attraction) to another and
      found both monotonic and nonmonotonic turnover behavior from adiabatic to
      nonadiabatic regimes. For the first time, we explore global dissipation by
      entropy production and the relation with binding/unbinding processes. Our
      theoretical predictions for steady state peaks, fano factos,
      inhibition/activation curves, and MFPT can be probed and tested from experiments.

PMID- 21189037
TI  - Spontaneous phase transfer of thermosensitive hairy particles between water and
      an ionic liquid.
AB  - This article describes the temperature-induced phase transfer behavior of a
      series of thermosensitive polymer brush-grafted particles between water and a
      hydrophobic ionic liquid, 1-ethyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide ([EMIM][TFSI]). Six samples were made by
      surface-initiated atom transfer radical polymerization: silica particles grafted
      with poly(methoxypoly(ethylene glycol) methacrylate) (PPEGMMA) with two different
      molecular weights, poly(methoxytri(ethylene glycol) methacrylate) (PTEGMMA),
      poly(methoxydi(ethylene glycol) methacrylate) (PDEGMMA), and two copolymers of
      PEGMMA and TEGMMA with different compositions (P(PEGMMA-co-TEGMMA)-82 and
      P(PEGMMA-co-TEGMMA)-74). The cloud points of free PPEGMMA with M(n,SEC) of 23 and
      40 kDa, P(PEGMMA-co-TEGMMA)-82, P(PEGMMA-co-TEGMMA)-74, and PTEGMMA in
      [EMIM][TFSI]-saturated water were 95, 94, 80, 72, and 43  degrees C,
      respectively. PDEGMMA was not soluble in the ionic liquid-saturated water.
      PPEGMMA brush-grafted particles moved spontaneously and completely from water to
      the [EMIM][TFSI] phase upon heating at 80  degrees C. When cooled to 22  degrees
      C, all particles returned to the water layer. From UV-vis absorbance
      measurements, the transfer temperature (T(tr)) of PPEGMMA-grafted particles from
      water to the ionic liquid was 42  degrees C. Thermodynamic analysis showed that
      the particle transfer was an entropically driven process. P(PEGMMA-co-TEGMMA)-82,
      P(PEGMMA-co-TEGMMA)-74, and PTEGMMA brush-grafted particles also underwent
      reversible and quantitative transfer between the two phases upon heating at 70 
      degrees C and cooling at 0  degrees C; their transfer temperatures from water to
      [EMIM][TFSI] were 36, 30, and 16  degrees C, respectively. T(tr) was a linear
      function of the cloud point of the corresponding free polymer in ionic liquid
      saturated water. In contrast, PDEGMMA-grafted particles moved spontaneously to
      the ionic liquid layer upon heating but did not return to water even after
      prolonged stirring at 0  degrees C.

PMID- 21189038
TI  - Transplantation of nanostructured composite scaffolds results in the regeneration
      of chronically injured spinal cords.
AB  - The destruction and hollowing of entire tissue segments represent an
      insurmountable barrier to axonal regeneration and therapeutics in chronic spinal
      cord injury. To circumvent this problem, we engineered neural prosthetics, by
      assembling electrospun nanofibers and self-assembling peptides into composite
      guidance channels and transplanted them into the cysts of a postcontusive,
      chronic spinal cord injury rat model, also providing delivery of proregenerative
      cytokines. Six months later conspicuous cord reconstruction was observed. The
      cyst was replaced by newly formed tissue comprising neural and stromal cells.
      Nerve fibers were interspersed between and inside the guidance channels, spanning
      the lesion, amidst a well-developed vascular network, basal lamina, and myelin.
      This was accompanied by a significant improvement in the activity of ascending
      and descending motor pathways and the global locomotion score. Thus by
      engineering nanostructured matrices into neuroprosthetics, it is possible to
      recreate an anatomical, structural, and histological framework, which leads to
      the replacement of large, hollow tissue gaps in the chronically injured spinal
      cord, fostering axonal regeneration and neurological recovery.

PMID- 21189039
TI  - Biotransformation of turmerones by Aspergillus niger.
AB  - Biotransformation studies conducted on (+)-(S)-ar-turmerone (1) and (+)-(S)
      dihydro-ar-turmerone (2) by the fungus Aspergillus niger have revealed that 1 was
      metabolized to give four oxidized metabolites, (+)-(7S)-hydroxydehydro-ar
      todomatuic acid (3), (+)-(7S,10E)-12-hydroxydehydro-ar-todomatuic acid (4), (+)
      (7S,10E)-7,12-dihydroxydehydro-ar-todomatuic acid (5), and (+)-(7S)-15-carboxy
      9,13-epoxy-7-hydroxy-9,13-dehydro-ar-curcumene (6), and (+)-(S)-dihydro-ar
      turmerone (2) was metabolized to (+)-7,11-dihydroxy-ar-todomatuic acid (7).
      Metabolites 3-7 were characterized using spectroscopic techniques. Metabolites 3
      7 inhibited acetylcholinesterase (AChE) although less so than the parent
      substrates.

PMID- 21189040
TI  - One-pot synthesis of visible-light-driven plasmonic photocatalyst Ag/AgCl in
      ionic liquid.
AB  - Plasmonic photocatalyst Ag/AgCl was prepared by in situ hydrothermal method with
      the contribution of 1-octyl-3-methylimidazolium chloride ([Omim]Cl), in which the
      [Omim]Cl ionic liquid acted not only as a precursor but also as a reducing
      reagent in the process of formation of Ag0. The samples were characterized by X
      ray diffraction (XRD), scanning electron microscopy (SEM), diffuse reflectance
      spectroscopy (DRS), X-ray photoelectron spectroscopy (XPS), and thermogravimetric
      and differential scanning calorimetry (TG-DSC). The photocatalytic activity of
      the composites were evaluated by degradation of methyl orange (MO) under visible
      light irradiation. The experimental results showed that the high activity and
      stability of Ag/AgCl photocatalysts under visible-light irradiation were due to
      their localized surface plasmon resonance (LSPR). Based on the characterization
      of the structure and photocatalytic performance, the LSPR was determined by
      synergetic effect of many factors, such as particle size of metallic Ag, contents
      of the Ag0 nanoparticles, and the extent of metallic Ag dispersing. A
      photocatalytic mechanism of the Ag/AgCl photocatalyst was also proposed.

PMID- 21189041
TI  - Controlled 3D buckling of silicon nanowires for stretchable electronics.
AB  - Silicon (Si) nanowire (NW) coils were fabricated on elastomeric substrates by a
      controlled buckling process. Si NWs were first transferred onto prestrained and
      ultraviolet/ozone (UVO)-treated poly(dimethylsiloxane) (PDMS) substrates and
      buckled upon release of the prestrain. Two buckling modes (the in-plane wavy mode
      and the three-dimensional coiled mode) were found; a transition between them was
      achieved by controlling the UVO treatment of PDMS. Structural characterization
      revealed that the NW coils were oval-shaped. The oval-shaped NW coils exhibited
      very large stretchability up to the failure strain of PDMS (~104% in our study).
      Such a large stretchability relies on the effectiveness of the coil shape in
      mitigating the maximum local strain, with a mechanics that is similar to the
      motion of a coil spring. Single NW devices based on coiled NWs were demonstrated
      with a nearly constant electrical response in a large strain range. In addition
      to the wavy shape, the coil shape represents an effective architecture in
      accommodating large tension, compression, bending, and twist, which may find
      important applications for stretchable electronics and other stretchable
      technologies.

PMID- 21189042
TI  - Self-assembled multicompartment liquid crystalline lipid carriers for protein,
      peptide, and nucleic acid drug delivery.
AB  - Lipids and lipopolymers self-assembled into biocompatible nano- and
      mesostructured functional materials offer many potential applications in medicine
      and diagnostics. In this Account, we demonstrate how high-resolution structural
      investigations of bicontinuous cubic templates made from lyotropic
      thermosensitive liquid-crystalline (LC) materials have initiated the development
      of innovative lipidopolymeric self-assembled nanocarriers. Such structures have
      tunable nanochannel sizes, morphologies, and hierarchical inner organizations and
      provide potential vehicles for the predictable loading and release of therapeutic
      proteins, peptides, or nucleic acids. This Account shows that structural studies
      of swelling of bicontinuous cubic lipid/water phases are essential for overcoming
      the nanoscale constraints for encapsulation of large therapeutic molecules in
      multicompartment lipid carriers. For the systems described here, we have employed
      time-resolved small-angle X-ray scattering (SAXS) and high-resolution freeze
      fracture electronic microscopy (FF-EM) to study the morphology and the dynamic
      topological transitions of these nanostructured multicomponent amphiphilic
      assemblies. Quasi-elastic light scattering and circular dichroism spectroscopy
      can provide additional information at the nanoscale about the behavior of
      lipid/protein self-assemblies under conditions that approximate physiological
      hydration. We wanted to generalize these findings to control the stability and
      the hydration of the water nanochannels in liquid-crystalline lipid nanovehicles
      and confine therapeutic biomolecules within these structures. Therefore we
      analyzed the influence of amphiphilic and soluble additives (e.g. poly(ethylene
      glycol)monooleate (MO-PEG), octyl glucoside (OG), proteins) on the nanochannels'
      size in a diamond (D)-type bicontinuous cubic phase of the lipid glycerol
      monooleate (MO). At body temperature, we can stabilize long-living swollen
      states, corresponding to a diamond cubic phase with large water channels. Time
      resolved X-ray diffraction (XRD) scans allowed us to detect metastable
      intermediate and coexisting structures and monitor the temperature-induced phase
      sequences of mixed systems containing glycerol monooleate, a soluble protein
      macromolecule, and an interfacial curvature modulating agent. These observed
      states correspond to the stages of the growth of the nanofluidic channel network.
      With the application of a thermal stimulus, the system becomes progressively more
      ordered into a double-diamond cubic lattice formed by a bicontinuous lipid
      membrane. High-resolution freeze-fracture electronic microscopy indicates that
      nanodomains are induced by the inclusion of proteins into nanopockets of the
      supramolecular cubosomic assemblies. These results contribute to the
      understanding of the structure and dynamics of functionalized self-assembled
      lipid nanosystems during stimuli-triggered LC phase transformations.

PMID- 21189043
TI  - Particle diffusion in globular protein gels in relation to the gel structure.
AB  - Globular protein gels with a variety of structures were prepared by heating beta
      lactoglobulin solutions at different concentrations and different ionic
      strengths. The structure was analyzed in terms of the pair correlation function
      of the protein concentration, and the volume fraction of the gels was determined.
      A strong coarsening of the gel structure was observed upon increasing the NaCl
      concentration between 0.1 and 0.25 M. The mean square displacement of spherical
      particles with diameters between 0.2 and 2 MUm was determined in solutions and in
      gels by multiparticle tracking of confocal laser scanning microscopy images.
      Brownian diffusion or trapping of spheres with different sizes was observed,
      depending on the gel structure. In few cases the diffusion was anomalous. The
      relationship between gel structure and particle mobility is discussed.

PMID- 21189044
TI  - Mechanical properties of the beetle elytron, a biological composite material.
AB  - We determined the relationship between composition and mechanical properties of
      elytra (modified forewings that are composed primarily of highly sclerotized
      dorsal and less sclerotized ventral cuticles) from the beetles Tribolium
      castaneum (red flour beetle) and Tenebrio molitor (yellow mealworm). Elytra of
      both species have similar mechanical properties at comparable stages of
      maturation (tanning). Shortly after adult eclosion, the elytron of Tenebrio is
      ductile and soft with a Young's modulus (E) of 44 +/- 8 MPa, but it becomes
      brittle and stiff with an E of 2400 +/- 1100 MPa when fully tanned. With
      increasing tanning, dynamic elastic moduli (E') increase nearly 20-fold, whereas
      the frequency dependence of E' diminishes. These results support the hypothesis
      that cuticle tanning involves cross-linking of components, while drying to
      minimize plasticization has a lesser impact on cuticular stiffening and frequency
      dependence. Suppression of the tanning enzymes laccase-2 (TcLac2) or aspartate 1
      decarboxylase (TcADC) in Tribolium altered mechanical characteristics consistent
      with hypotheses that (1) ADC suppression favors formation of melanic pigment with
      a decrease in protein cross-linking and (2) Lac2 suppression reduces both
      cuticular pigmentation and protein cross-linking.

PMID- 21189045
TI  - Single-stranded DNA binding proteins unwind the newly synthesized double-stranded
      DNA of model miniforks.
AB  - Single-stranded DNA binding (SSB) proteins are essential proteins of DNA
      metabolism. We characterized the binding of the bacteriophage T4 SSB, Escherichia
      coli SSB, human replication protein A (hRPA), and human hSSB1 proteins onto model
      miniforks and double-stranded-single-stranded (ds-ss) junctions exposing 3' or 5'
      ssDNA overhangs. T4 SSB proteins, E. coli SSB proteins, and hRPA have a different
      binding preference for the ss tail exposed on model miniforks and ds-ss
      junctions. The T4 SSB protein preferentially binds substrates with 5' ss tails,
      whereas the E. coli SSB protein and hRPA show a preference for substrates with 3'
      ss overhangs. When interacting with ds-ss junctions or miniforks, the T4 SSB
      protein, E. coli SSB protein, and hRPA can destabilize not only the ds part of a
      ds-ss junction but also the daughter ds arm of a minifork. The T4 SSB protein
      displays these unwinding activities in a polar manner. Taken together, our
      results position the SSB protein as a potential key player in the reversal of a
      stalled replication fork and in gap repair-mediated repetitive sequence
      expansion.

PMID- 21189046
TI  - Assessing the prevalence of trauma exposure in epidemiological surveys.
AB  - OBJECTIVE: Estimates of the prevalence of exposure to potentially traumatic
      events (PTEs) in population surveys have increased over time. There is limited
      empirical evidence on the impact of changes in measurement practices on these
      estimates. The present study examined the effect of increasing the number of
      events assessed on the prevalence of exposure longitudinally. METHODS: Data were
      ultilized from the 1997 and 2007 Australian National Surveys of Mental Health and
      Wellbeing. The 1997 survey assessed exposure using 11 items from the Composite
      International Diagnostic Interview (CIDI), version 2.1. The 2007 survey utilized
      29 items from the World Mental Health CIDI. Prevalence rates of exposure to
      matched events among age-matched samples from both surveys were compared to
      determine whether differences in the estimates obtained were due to respondents
      having been asked about an increased number of event types in the latter survey.
      RESULTS: The effect of increasing the number of event types in the CIDI from 11
      to 29 was to increase the overall population prevalence of exposure to PTEs by
      18%. The difference between estimates was more pronounced in women than in men.
      The cross-cohort analyses revealed that these differences were not indicative of
      an increase in trauma exposure over time; but rather the endorsement of new
      events that were not listed in the earlier survey. CONCLUSIONS: The findings
      underscore the importance of using comprehensive assessments in the measurement
      of exposure to PTEs. Previous epidemiological surveys may have underestimated the
      prevalence of traumatic and other stressful life events, particularly among
      women.

PMID- 21189047
TI  - Clinical outcome of catheter salvage in neutropenic cancer patients with catheter
      related infection.
AB  - BACKGROUND: Catheter-related infections (CRI) cause significant morbidity and
      mortality in cancer patients, particularly during episodes of chemotherapy
      induced neutropenia. This study was performed to evaluate clinical features and
      outcomes of CRI in neutropenic cancer patients. METHODS: We retrospectively
      analyzed clinical characteristics and outcome of febrile neutropenic cancer
      patients with CRI who visited the emergency department from January 1996 to June
      2007. RESULTS: A total of 51 neutropenic cancer patients with CRI were identified
      and 53 organisms were isolated from culture specimens. The mean +/- standard
      deviation patient age was 50 +/- 15 y and the most common underlying disease was
      lymphoma (n = 27, 53%). Gram-positive organisms accounted for 77% of all isolated
      pathogens (41/53). Initial catheter salvage was attempted in 38 episodes of CRI,
      of which 20 were successful. In the current study the overall success rate of
      catheter salvage attempts was 52.6%. The failure rate of catheter salvage was
      significantly higher in CRI caused by Gram-negative pathogens than by Gram
      positive pathogens. CONCLUSION: Although catheter salvage should be cautiously
      attempted for cancer patients with CRI, it might not be a treatment option for
      neutropenic cancer patients with CRI caused by Gram-negative bacteria.

PMID- 21189048
TI  - Risk factors for sleep-disordered breathing: the role of craniofacial structure.
AB  - OBJECTIVE: To evaluate possible differences in craniofacial structure between
      overweight patients and normal-weight patients with mild sleep-disordered
      breathing (SDB). MATERIAL AND METHODS: Subjects were recruited from patients
      referred to Kuopio University Hospital due to suspicion of SDB. They were divided
      into two groups based on their body mass index (BMI). The overweight group (BMI >
      27 kg/m(2)) consisted of 58 males and 19 females and the normal weight group (BMI
      <= 27 kg/m(2)) of 33 males and 15 females. The mean age of the subjects was 51.4
      years. All subjects underwent an overnight cardiorespiratory recording. The mean
      apnea-hypopnea index (AHI) was 9.3 events/h for the entire study population.
      Occlusion and craniofacial morphology were examined by an experienced
      orthodontist. RESULTS: Significant differences in craniofacial morphology and
      occlusion were found between the groups: the craniofacial profile in normal
      weight patients was more convex (P < 0.000) and the mandible more retrusive (P =
      0.004) than in overweight subjects. In addition, distal molar occlusion (P =
      0.005) was more prevalent in normal-weight subjects, and their overjet and
      overbite were increased as compared to overweight patients (P = 0.009 and 0.006,
      respectively). Similarly, cross bite was detected significantly more often in
      normal-weight subjects (P = 0.052). CONCLUSIONS: These results reveal that
      deviations in craniofacial morphology and occlusion are more frequent in normal
      subjects than in overweight subjects with mild SDB; this may well have
      implications in the pathophysiology of SDB.

PMID- 21189049
TI  - Preventative effect of various fluids used in the epitympanic bulla on
      deterioration of cochlear function during labyrinthectomy.
AB  - CONCLUSION: Preventing leakage of endolymph during vestibular destruction may be
      important in the acute phase. OBJECTIVES: Vestibulotomy causes significant
      decrease in the endocochlear potential (EP). The effect of artificial perilymph
      and distilled water administration during vestibulotomy on hearing preservation
      was evaluated in Hartley guinea pigs. METHODS: Animals were divided into three
      groups: the epitympanic bulla was filled with artificial perilymph or distilled
      water, or was not filled with any solution (control group). The EP and [K(+)]
      were monitored using double-barrelled ion-selective microelectrodes in the second
      turn of the cochlea. RESULTS: EP was not significantly different between the
      artificial perilymph and the distilled water groups, although both groups showed
      better preservation of EP compared with the control group. The [K(+)] was not
      significantly different between the three groups.

PMID- 21189050
TI  - Cyclo-oxygenase enzyme in the perilymph of human inner ear.
AB  - CONCLUSIONS: Cyclo-oxygenase-2 (COX-2) enzyme would not appear to be
      constitutively expressed in human perilymph while it is always induced in the
      perilymph of patients affected by sensorineural hearing loss (SNHL). The COX-2
      isoform may be involved in hearing loss and, therefore, pathological states of
      the inner ear should possibly be further analyzed to clarify the clinical
      relevance of prostaglandin and selective COX-2 antagonist therapy. OBJECTIVES:
      Perilymph samples from a group of patients with bilateral SNHL and another with
      conductive hearing loss were collected to evaluate the presence of the COX-2
      enzyme. The possible correlation between different causes of deafness and the
      expression of COX-2 in the human ear was studied. METHODS: A prospective clinical
      study of 14 patients with severe or profound hearing loss who underwent cochlear
      implant surgery and 4 patients with conductive hearing loss who underwent stapes
      surgery was carried out. Western blot analysis of perilymph samples was performed
      with monoclonal anti-human COX-2 antibody. RESULTS: COX-2 enzyme was detected in
      all patients affected by SNHL and was absent in all those with conductive hearing
      loss due to otosclerosis.

PMID- 21189051
TI  - The acoustic cortex in frontotemporal dementia: a Golgi and electron microscope
      study.
AB  - CONCLUSION: The neuronal loss and the alteration of the synapses in the acoustic
      cortex in frontotemporal dementia (FTD) may be related to the impairment of
      communication and symbolic sound perception, which is noticed in the majority of
      the cases. OBJECTIVES: FTD is a heterogeneous neurodegenerative disorder, causing
      progressive decline of intellectual faculties, impairment of behavior and social
      performance, and impairment of speech eloquence, associated with various
      neurological manifestations based on a variable neuropathological background. We
      attempted to determine the morphological alterations of the dendrites and the
      dendritic spines in the acoustic cortex of 10 cases who fulfilled the diagnostic
      criteria for FTD. METHODS: For the histological study we applied (a) routine
      neuropathological techniques and (b) rapid Golgi method. We proceeded to electron
      microscopy for the ultrastructural study of the synapses and the morphological
      and morphometric study of the organelles, the dendrites, and the dendritic
      spines. RESULTS: The morphological and morphometric analysis revealed substantial
      neuronal loss and synaptic alterations in the acoustic cortex in all the cases of
      FTD and particularly in Pick disease and in primary progressive aphasia.
      Mitochondria alterations and changes of the Golgi apparatus were seen mostly in
      Pick disease.

PMID- 21189052
TI  - The perceived angle of the round window affects electrode insertion trauma in
      round window insertion - an anatomical study.
AB  - CONCLUSION: In this study round window (RW) insertion of cochlear implant was
      performed with a lower degree of trauma in 86.6% of cases. Therefore RW insertion
      is a valid option to be considered in selected cochlear implant patients,
      especially when hearing preservation is a goal. In most cases drilling of the
      overhangs is required. OBJECTIVES: To systematically examine the potential for
      minimizing electrode insertion trauma with RW insertion. METHODS: Fifteen
      temporal bones were inserted with a 0.5 mm electrode analog in an anterior or
      antero-inferior vector from a reference point along the facial recess. Surface
      preparation of the inferior segment of the basal turn was performed and the point
      of first contact was analyzed using computerized morphometric software. The same
      software was used to measure the RW dimensions before and after drill down of the
      bony overhangs. An insertion was considered 'traumatic' if the point of first
      contact was the medial wall of the scala, whereas 'less traumatic' was an
      insertion in which the point of first contact was the inferior or posterior wall
      of the scala. RESULTS: Less traumatic insertion was achieved in 13 of the 15
      bones, and in these the mean RW angle, as observed from a surgical point of view,
      was 137 degrees . The mean RW angle in the traumatic insertion group was 147
      degrees . The difference was statistically significant.

PMID- 21189053
TI  - Clinical characteristics of positional vertigo after mild head trauma.
AB  - CONCLUSION: This study showed that a population with benign paroxysmal positional
      vertigo related to mild head trauma (BPPVAT) was younger and more frequently
      presented with bilateral canalithiasis than another population with idiopathic
      etiology (IBPPV). In both groups, females presented a higher risk of BPPV.
      OBJECTIVE: To compare the clinical features of a population with BPPVAT and
      another with IBBPV. METHODS: We carried out statistical analysis of a population
      of 51 subjects with BPPVAT and another of 325 subjects with IBPPV, comparing age,
      gender, recurrence of symptoms, associated chronic dizziness (CD), and clinical
      presentation. Kolmogorov Smirnov test, Student's t test, Mann-Whitney test, 95%
      binomial confidence interval for proportions, chi-squared, and Fisher's test were
      used as statistical tools. A significance level of p < 0.05 was considered in all
      cases. RESULTS: The population affected with BPPVAT was younger and bilateral
      canalithiasis was also more frequent. No differences were found in gender
      distribution, semicircular canals involved in the symptoms, recurrence after
      repositioning maneuvers, or associated CD.

PMID- 21189054
TI  - Cyclic estrogenic fluctuation influences synaptic transmission of the medial
      vestibular nuclei in female rats.
AB  - CONCLUSION: The estrous cycle in female rats influences the basal synaptic
      responsiveness and plasticity of the medial vestibular nucleus (MVN) neurons
      through different levels of circulating 17beta-estradiol (cE(2)). OBJECTIVE: The
      aim of this study was to verify, in the female rat, whether cyclic fluctuations
      of cE(2) influence long-term synaptic effects induced by high frequency afferent
      stimulation (HFS) in the MVN, since we found that HFS in the male rat induces
      fast long-term potentiation (fLTP), which depends on the neural synthesis of E(2)
      (nE(2)) from testosterone (T). METHODS: We analyzed the field potential (FP)
      evoked in the MVN by vestibular afferent stimulation, under basal conditions, and
      after HFS, in brainstem slices of female rats during high levels (proestrus, PE)
      and low levels (diestrus, DE) of cE(2). Selective blocking agents of converting T
      enzymes were used. RESULTS: Unlike in the male rat, HFS induced three effects:
      fLTP through T conversion into E(2), and slow LTP (sLTP) and long-term depression
      (LTD), through T conversion into DHT. The occurrence of these effects depended on
      the estrous cycle phase: the frequency of fLTP was higher in DE, and those of
      sLTP and LTD were higher in PE. Conversely, the basal FP was also higher in PE
      than in DE.

PMID- 21189055
TI  - The specific IgE reactivity pattern of weed pollen-induced allergic rhinitis
      patients.
AB  - CONCLUSION: Specific immunoglobulin E (IgE) reactivity towards the major mugwort
      allergen Art v 1 is a good indicator for Art v sensitization. Allergens from the
      ragweed species Amb t and Amb a possibly share common IgE-binding epitopes.
      OBJECTIVE: The aim of this study was to investigate the reactivity pattern of IgE
      in Chinese patients with weed pollen-induced allergic rhinitis. METHODS: Sera
      from 50 weed pollen-induced allergic rhinitis patients were tested for specific
      serum IgE reactivity against allergenic extracts of mugwort (Artemisia vulgaris,
      Art v), short ragweed (Ambrosia artemisiifolia, Amb a), giant ragweed (Ambrosia
      trifida, Amb t), and single allergens of Art v 1, Art v 3, Amb a 1, and profilin.
      RESULTS: Sera from 88% of the patients demonstrated positive specific IgE
      reactivity to Art v, and of these 82% were positive to Art v 1. Sera from 38% of
      the patients showed positive specific IgE reactivity to both ragweed species Amb
      t and Amb a. A strong correlation was found between the specific IgE levels of
      Amb t and Amb a. Of the Amb a IgE-positive patients, 38% were positive for Amb a
      1. Of all patient sera tested, 12% were specific IgE-positive to profilin.

PMID- 21189057
TI  - Changing pattern of Candida species in a neonatal intensive care unit.

PMID- 21189056
TI  - Symptoms of ADHD and depression in a large adolescent population: co-occurring
      symptoms and associations to experiences of sexual abuse.
AB  - BACKGROUND: Symptoms of either attention-deficit hyperactivity disorder (ADHD) or
      depression constitute the most common reasons for contact with child and
      adolescent psychiatry. The development of psychiatric symptoms can be explained
      by a combination of environmental stress events and genetic vulnerability. One
      common form of environmental stress with high impact on health is sexual abuse.
      AIMS: To investigate the prevalence and co-occurrence of symptoms of ADHD and
      depression in relation to experiences of sexual abuse in a large adolescent
      general population. METHOD: All 15- and 18-year-old students (n = 4910) in the
      Swedish county of Vestmanland answered a school-based screening instrument
      including the six-question ADHD self-rating scale (ASRS), the Depression Self
      Rating Scale (DSRS) and questions relating to experiences of sexual abuse.
      RESULTS: The prevalence of co-occurring symptoms of ADHD and depression was 2.4%
      (boys 1.0%, girls 3.9%). The prevalence of experience of any sexual abuse was
      20.9% (boys 13.3%, girls 28.7%). Of those with co-occurring symptoms, 48% of the
      boys and 47% of the girls reported a history of sexual abuse. CONCLUSIONS: School
      based screening for co-occurring symptoms of ADHD and depression might be a
      method that identifies students at psychiatric and psychosocial risk.

PMID- 21189058
TI  - Mechanomyography as an access pathway: corporeal contraindications.
AB  - PURPOSE: The purpose of this study is to delineate the impairments of body
      functions and structures which specifically inhibit mechanomyography (MMG)-based
      switch control as an alternative access pathway. METHOD: Seven individuals with
      severe physical disabilities and varied diagnoses of neuromuscular or
      neurological conditions tested a MMG switch. A semi-structured protocol was used
      to gather quantitative and qualitative indications of the switch's performance,
      and descriptive perceptions of the participants and their care givers. RESULTS:
      The participants controlled the switch by contracting muscles of their forehead,
      forearm or shoulder. Body functions and structures that negatively affect the
      signal-to-noise ratio (SNR) of the recorded MMG signal included involuntary
      dystonic movement, impaired muscle control, atrophied muscles, muscle spasticity
      and involuntary activity of neighbouring muscles. CONCLUSIONS: The MMG switch is
      strongly recommended where the muscle site and its control are intact and signal
      artefact is minimal. Its viability when muscle activity at the access site may be
      confounded by signal artefact is dependent on the strength of the voluntary
      muscle contraction relative to that of artefacts such as spastic contractions,
      involuntary dystonic movements, muscle spasms and physiological vibrations.
      Neurological conditions, such as spasticity, that compromise the user's ability
      to voluntarily contract or suppress muscle contractions may be considered
      contraindications to MMG-based access.

PMID- 21189059
TI  - Feasibility of three electronic instruments in studying the benefits of adaptive
      seating.
AB  - PURPOSE: This pilot study assesses the suitability of three electronic
      instruments for the potential to objectively and consistently measure the
      effectiveness of adaptive seating for children with neuromotor disorders such as
      cerebral palsy and muscular dystrophy. METHOD: A MiniMicroactigraph, an XSens
      accelerometer and an Xsensor pressure mapping system were assessed for their
      ability to measure change in five participants' stability, movement and posture
      when seating in a flat CAPS II chair and a contoured CAPS II chair. RESULTS: The
      accelerometer and pressure mapping system showed a difference in amount of
      movement and body/seat interface between two contrasting seated surfaces on all
      children, demonstrating potential for use in future research. The results of the
      actigraph were inconclusive, but did highlight the importance of instrument
      placement for future studies that utilise this technology. CONCLUSION: The three
      instruments have potential suitability for use in future, more comprehensive
      studies of adaptive seating. It is recommended that future studies explore the
      additional features of these instruments for their potential to provide objective
      data regarding the effects of adaptive seating on children's postural alignment
      and support, pressure management, stability, functional ability and comfort.

PMID- 21189060
TI  - Novel poly-DL-lactide-polycaprolactone copolymer based flexible drug delivery
      system for sustained release of ciprofloxacin.
AB  - This research evaluated 7525DLPCL for soft flexible drug delivery systems. The
      effect of ciprofloxacin hydrochloride (CIP) loading at three levels (10, 20, and
      30%), on thermo-mechanical properties was studied. CIP release was monitored for
      12 weeks. Addition of CIP to 7525DLPCL caused an increase in compressive modulus
      of 7525DLPCL. CIP release was found to be sigmoidal with two phenomena (apart
      from a minor burst) contributing to release-diffusion and later diffusion plus
      erosion. An increased burst was observed with greater CIP loading and the
      majority of CIP (> 70%) was released as an effect of diffusion plus erosion.
      Additional factors, like the effect of CIP particle size, had no significant
      effect on drug release. Change in the implant shape from a cylinder (5 mm
      diameter; 3 mm thickness) to disc (6 mm diameter, 0.5 mm thickness) also failed
      to show a significant impact on drug release. Erosion of 7525DLPCL is a major
      contributing factor towards this release and other factors like shape of implants
      and particle size of drug have little effect on CIP release. Such flexible drug
      delivery systems offer new avenues for long-term skeletal drug delivery of
      antibiotics for conditions like osteomyelitis or periodontitis.

PMID- 21189061
TI  - Spleen tyrosine kinase modulates the proliferation and phenotypes of vascular
      smooth muscle cells induced by platelet-derived growth factor.
AB  - Platelet-derived growth factor BB (PDGF-BB) regulates vascular smooth muscle
      cells (VSMCs) by activating signaling cascades that promote vasoconstriction and
      growth, but the underlying mechanisms remain incompletely characterized. In this
      study, we aimed at investigating the role of spleen tyrosine kinase (Syk) in the
      proliferation and phenotypes in rat pulmonary arterial VSMCs. Our results
      demonstrate that PDGF-BB or Syk-adenovirus led to a substantial increase of
      proliferation of VSMCs and cytoskeleton rearrangement in rat VSMCs. Consistently,
      these cells underwent phenotype changes. Notably, Syk inhibitor piceatannol
      significantly inhibited those biological effects induced by PDGF-BB. Thus, we
      conclude that Syk plays an important role in vascular remodeling through the
      modulation of proliferation and phenotypes of VSMCs.

PMID- 21189065
TI  - Interactions between small ubiquitin-like modifier 1 and nonsyndromic orofacial
      clefts.
AB  - Small ubiquitin-like modifier 1 (SUMO1) and environmental factors have been shown
      to be associated with nonsyndromic cleft lip with or without cleft palate
      (NSCL/P) in several populations. This study aimed at confirming the contribution
      of SUMO1 gene and environmental factors to nonsyndromic orofacial clefts risk in
      western Han Chinese. Four single-nucleotide polymorphisms were investigated in
      212 case trios in western China using conditional logistic regression models and
      the transmission disequilibrium test under a case-parent trio design. Strong
      evidence of linkage and linkage disequilibrium was found between these markers
      and the disease in both single-nucleotide polymorphism analysis (T allele at
      rs6761234 [p = 0.0005, odds ratio [OR] = 1.82, 95% confidence interval [CI]:1.30
      2.57) and C allele at rs12470401 (p < 0.0001, OR = 2.82, 95% CI: 1.90-4.19)] and
      sliding window haplotype analysis (T-T-T for rs6761234-rs12470401-rs7599810 [p =
      0.018], C-C-G for rs12470401-rs7599810-rs6435133 [0.0033], C-T-T-T for rs6761234
      rs12470401-rs7599810-rs6435133 [p = 0.018] among others). Interactions between
      mothers' passive smoking during the first trimester and C/C genotype of
      rs12470401 showed statistical significance (OR(0) = 2.53 and OR(1) = 8.83). Risk
      factors identified in this study may provide a better understanding of the
      etiological role of SUMO1 gene in NSCL/P incidence.

PMID- 21189066
TI  - Two novel SNPs in HSF1 gene are associated with thermal tolerance traits in
      Chinese Holstein cattle.
AB  - Heat-shock transcription factors (HSFs) play an important role in regulating heat
      stress response. The activation of heat-shock protein (HSP) genes is mediated by
      HSFs, which bind to promoters of HSP genes. In this research, two novel single
      nucleotide polymorphisms, T909C and G4693T, and their association with thermal
      tolerance were investigated in 951 Chinese Holstein cattle. Linkage
      disequilibrium and haplotype construction were analyzed using SHEsis software.
      Four haplotypes were constructed, and nine haplotype combinations were found.
      Potassium content in erythrocytes (PCE), decreased rate of milk production (R),
      rectal temperature (RT), and heat-tolerance coefficient (HTC) were selected for
      the thermotolerance index. Association analysis showed that thermal tolerance in
      Chinese Holstein cattle was significantly affected by T909C and G4693T. The PCE
      of cows with CC or TC genotype was lower than that of TT at the 909 position (p <
      0.05). Cows with TT genotype had lower PCE (p < 0.01) and higher HTC (p < 0.05)
      at the 4693 position. Cows with H2H4 haplotype combination had lower PCE (p <
      0.01), R (p < 0.05) and RT (p < 0.05) and higher HTC (p < 0.05) than those with
      H1H3 haplotype combination. Bioinformatic analysis predicted that the 4693
      position was located in the microRNA-binding (bta-miR-484) region. Quantitative
      reverse transcription-polymerase chain reaction demonstrated that 4693-T mutation
      caused the disruption of microRNA target binding, resulting in the relief of the
      transcriptional repression, which, in turn, resulted in increased expression.
      Thus, the HSF1 gene is useful in dairy cattle thermal tolerant breeding.

PMID- 21189067
TI  - Human leukocyte antigen-DRB1 class II genes in Mexican Amerindian Mazahuas: genes
      and languages do not correlate.
AB  - BACKGROUND: The major histocompatibility complex genes are located on the short
      arm of the human sixth chromosome; they are highly polymorphic and therefore have
      been very advantageous in population genetic studies. METHODS: A Mazahua group
      established in North Mexico State and also in nearby Michoacan state in the rainy
      mountain highlands (Mexico) was studied for their human leukocyte antigen (HLA)
      DRB1 alleles. The relationship with other Amerindians and worldwide populations
      was studied by using 14,996 chromosomes from 75 different populations and
      calculating neighbor-joining dendrograms and correspondence multidimensional
      values. RESULTS: Five principal HLA allele frequencies were found in our group:
      DRB1*0802 (the most frequent one in this population), DRB1*0407, DRB1*0403,
      DRB1*0101, and DRB1*1406. Both genetic distances and correspondence analyses
      clearly show that our Mazahua group is genetically close to some of the most
      ancient groups living in Mexico (Mayos, Zapotecans, Tennek) and South American
      Amerindians. Amerindians remain as a group apart from the rest of the world.
      CONCLUSIONS: The results analyzing the HLA-DR locus suggest that Mazahua language
      (Otomangue) does not correlate with those of the most closely HLA-correlated
      ethnic groups. The present data may be useful for future transplantation
      programs, HLA and disease diagnosis, and pharmacogenetic studies.

PMID- 21189068
TI  - Osteochondral tissue formation through adipose-derived stromal cell
      differentiation on biomimetic polycaprolactone nanofibrous scaffolds with graded
      insulin and Beta-glycerophosphate concentrations.
AB  - The ability to fabricate tissue engineering scaffolds containing systematic
      gradients in the distributions of stimulators provides additional means for the
      mimicking of the important gradients observed in native tissues. Here the
      concentration distributions of two bioactive agents were varied concomitantly for
      the first time (one increasing, whereas the other decreasing monotonically) in
      between the two sides of a nanofibrous scaffold. This was achieved via the
      application of a new processing method, that is, the twin-screw extrusion and
      electrospinning method, to generate gradients of insulin, a stimulator of
      chondrogenic differentiation, and beta-glycerophosphate (beta-GP), for
      mineralization. The graded poly(E-caprolactone) mesh was seeded with human
      adipose-derived stromal cells and cultured over 8 weeks. The resulting tissue
      constructs were analyzed for and revealed indications of selective
      differentiation of human adipose-derived stromal cells toward chondrogenic
      lineage and mineralization as functions of position as a result of the
      corresponding concentrations of insulin and beta-GP. Chondrogenic differentiation
      of the stem cells increased at insulin-rich locations and mineralization
      increased at beta-GP-rich locations.

PMID- 21189069
TI  - Matrigel improves functional properties of primary human salivary gland cells.
AB  - Currently, there is no effective treatment available to patients with
      irreversible loss of functional salivary acini caused by Sjogren's syndrome or
      after radiotherapy for head and neck cancer. A tissue-engineered artificial
      salivary gland would help these patients. The graft cells for this device must
      establish tight junctions in addition to being of fluid-secretory nature. This
      study analyzed a graft source from human salivary glands (huSG) cultured on
      Matrigel. Cells were obtained from parotid and submandibular glands, expanded in
      vitro, and then plated on either Matrigel-coated (2 mg/mL) or uncoated culture
      dish. Immunohistochemistry, transmission electron microscopy, quantitative real
      time-polymerase chain reaction, Western blot, and transepithelial electrical
      resistance were employed. On Matrigel, huSG cells adopted an acinar phenotype by
      forming three-dimensional acinar-like units (within 24 h of plating) as well as a
      monolayer of cells. On uncoated surfaces (plastic), huSG cells only formed
      monolayers of ductal cells. Both types of culture conditions allowed huSG cells
      to express tight junction proteins (claudin-1, -2, -3, -4; occludin; JAM-A; and
      ZO-1) and adequate transepithelial electrical resistance. Importantly, 99% of
      huSG cells on Matrigel expressed alpha-amylase and the water channel protein
      Aquaporin-5, as compared to <5% of huSG cells on plastic. Transmission electron
      microscopy confirmed an acinar phenotype with many secretory granules. Matrigel
      increased the secretion of alpha-amylase two to five folds into the media,
      downregulated certain salivary genes, and regulated the translation of acinar
      proteins. This three-dimensional in vitro serum-free cell culture method allows
      the organization and differentiation of huSG cells into salivary cells with an
      acinar phenotype.

PMID- 21189070
TI  - Chondrogenesis of rabbit mesenchymal stem cells in fibrin/hyaluronan composite
      scaffold in vitro.
AB  - Scaffold material is expected to play a crucial role in induction of chondrogenic
      differentiation of mesenchymal stem cells (MSCs) for cartilage tissue
      engineering. Here we demonstrated the feasibility of a fibrin/hyaluronan (HA)
      composite hydrogel as a potent scaffold for support of chondrogenesis of rabbit
      MSCs (rMSCs). rMSCs were prepared in three-dimensional cultures of pellet,
      alginate layer, and fibrin/HA gel. Specimens in each group were cultured in
      chondrogenic defined media for 4 weeks in the absence or presence of transforming
      growth factor beta1 (TGF-beta1) treatment. Viability of rMSCs was somewhat
      reduced until 4 weeks, which was less significant in fibrin/HA gels than in the
      alginate layer (*p < 0.05). The fibrin/HA group showed transient size reduction
      by about 35% at 1 week, but showed significantly higher mechanical strength than
      the alginate group. In safranin-O and alcian blue stains, accumulation of
      sulfated glycosaminoglycans (GAGs) was observed clearly from 1 week, and
      homogenously in the entire area at 4 weeks in the fibrin/HA group. Of note, TGF
      beta1 treatment showed no additional effect on GAGs accumulation in the fibrin/HA
      group. The alginate and pellet groups, however, showed much lower levels of GAGs
      accumulation only in the presence of TGF-beta1. Biochemical assays for GAGs and
      collagen, and expression of chondrogenic markers also showed much better results
      in the fibrin/HA group, even without TGF-beta treatment than the other groups.
      These results demonstrated that fibrin/HA composite gel efficiently promoted
      chondrogenic differentiation of rMSCs, even without TGF-beta treatment, and that
      it could be a useful tool for use in cartilage tissue engineering.

PMID- 21189071
TI  - Preclinical assessment of a tissue-engineered vasomotive human small-calibered
      vessel based on a decellularized xenogenic matrix: histological and functional
      characterization.
AB  - OBJECTIVES: Tissue-engineered arterial vessels (TEAV) offer substantial
      advantages in small-calibered human-bypass-grafting and vascularized scaffold
      applications. However, histological composition of TEAV must allow for functional
      properties, such as vasomotoricity. Aim of this study was to characterize human
      TEAVs regarding morphology and vasomotoricity. METHODS: Three groups containing
      segments of porcine carotid artery < 5 mm in diameter (native [NA, n = 6],
      decellularized [DA, n = 6], and decellularized/reseeded in a bioreactor [RA, n =
      7] with human vascular endothelial [hvECs] and smooth muscle cells [hvSMCs]) were
      examined. Light and scanning electron microscopy were applied, and hvSMCs- and
      hvECs-associated Vasomotoricity Test conducted in Krebs-solution was used for
      characterization of revitalized TEAVs. RESULTS: Morphologic examination showed
      cell-free extracellular matrix in DAs. Light microscopy demonstrated intact
      extracellular matrix components in circle-layered formation in cross sections of
      DAs. RAs showed small cells migrating along the remaining medial fiber structures
      and flat cell layers at the luminal site, identified as hvECs and hvSMCs with
      lower CD-31 and alpha-actin signaling than controls. Scanning electron microscopy
      showed intact flat cell layers on luminal surfaces of RAs and dense hvSMCs at
      their media site. DAs showed decreasing strain after stimulation. RAs retrieved
      vasomotoricity compared to DAs, but showed reduced contraction and incomplete
      relaxation compared to NAs. CONCLUSIONS: This study shows that revitalization of
      DA with human vascular cells resembles NA-like morphology and can ensure
      vasomotoricity of TEAVs.

PMID- 21189072
TI  - Sustained growth factor delivery promotes axonal regeneration in long gap
      peripheral nerve repair.
AB  - The aim of this study was to evaluate the long-term effect of localized growth
      factor delivery on sciatic nerve regeneration in a critical-size (> 1 cm)
      peripheral nerve defect. Previous work has demonstrated that bioactive proteins
      can be encapsulated within double-walled, poly(lactic-co-glycolic
      acid)/poly(lactide) microspheres and embedded within walls of biodegradable
      polymer nerve guides composed of poly(caprolactone). Within this study, nerve
      guides containing glial cell line-derived neurotrophic factor (GDNF) were used to
      bridge a 1.5-cm defect in the male Lewis rat for a 16-week period. Nerve repair
      was evaluated through functional assessment of joint angle range of motion using
      video gait kinematics, gastrocnemius twitch force, and gastrocnemius wet weight.
      Histological evaluation of nerve repair included assessment of Schwann cell and
      neurofilament location with immunohistochemistry, evaluation of tissue
      integration and organization throughout the lumen of the regenerated nerve with
      Masson's trichrome stain, and quantification of axon fiber density and g-ratio.
      Results from this study showed that the measured gastrocnemius twitch force in
      animals treated with GDNF was significantly higher than negative controls and was
      not significantly different from the isograft-positive control group.
      Histological assessment of explanted conduits after 16 weeks showed improved
      tissue integration within GDNF releasing nerve guides compared to negative
      controls. Nerve fibers were present across the entire length of GDNF releasing
      guides, whereas nerve fibers were not detectable beyond the middle region of
      negative control guides. Therefore, our results support the use of GDNF for
      improved functional recovery above negative controls following large axonal
      defects in the peripheral nervous system.

PMID- 21189073
TI  - Correlation between occlusal forces and marginal bone levels around implant
      retained restorations: a clinico-radiological study.
AB  - The study measured the maximal occlusal forces (MOFs) and marginal bone levels
      (MBLs) around single implant-retained restorations over a period of 1 year and
      studied the correlation between them. Results showed that there was no change in
      MOFs at the end of 1 year and that the MBLs were stabilized by the end of 1 year.
      There was no statistically significant correlation between MOFs and MBLs.

PMID- 21189081
TI  - The influence of maximum bite force on patient satisfaction and quality of life
      of patients wearing mandibular implant overdentures.
AB  - The treatment of edentulism with traditional complete dentures can often induce
      impaired masticatory function due to limited retention and stability, especially
      in the lower jaw. Mandibular interforaminal implants have been widely used to
      stabilize the dentures, consequently improving masticatory performance in
      edentulous individuals. The aim of the present study was to document the
      influence of this improved masticatory function on patient satisfaction and
      quality of life of patients wearing mandibular implant-supported overdentures.
      Sixty-two patients treated with various types of implant-supported mandibular
      overdentures between 2004 and 2007 were included in this retrospective study.
      Maximum bite force (MBF) was measured bilaterally using a device with 2 strain
      gauges connected to a strain gauge measurement system. All the included patients
      were asked to fill out visual analog scale (VAS) forms based on general and
      chewing satisfaction and OHIP-14 forms. Results were analyzed by the Spearman rho
      test. No statistically significant correlation was found between MBF values and
      VAS general or VAS chewing satisfaction or Oral Health Impact Profile scores (P >
      .05). The results indicate that MBF is not associated with the satisfaction or
      quality of life of implant-supported mandibular overdenture wearers.

PMID- 21189082
TI  - Nicotine-induced damage affects gingival fibroblasts in the gingival tissue of
      rats.
AB  - BACKGROUND: Very limited information is available from in vivo studies about
      whether smoking and/or nicotine affect gingival tissues in the absence of plaque.
      The purpose of this study is to evaluate the effect of the systemic
      administration of nicotine in the proliferation and counting of fibroblast-like
      cells in the gingival tissue of rats. METHODS: Thirty adult male Wistar rats were
      randomly assigned into two groups to receive subcutaneous injections of a saline
      solution (control group = group C) or nicotine solution (group N; 3 mg/kg) twice
      a day. The animals were euthanized 37, 44, or 51 days after the first
      subcutaneous injection. Specimens were routinely processed for serial histologic
      sections. Five fields of view in the connective tissue adjacent to the gingival
      epithelium and above the alveolar bone crest of the maxillary first molar were
      selected for the counting of fibroblast-like cells. Data were statistically
      analyzed (P <0.05). RESULTS: The intergroup analysis detected a lower number of
      fibroblast-like cells in group N compared to group C on days 37 (2.65 +/- 1.41
      and 6.67 +/- 3.25, respectively), 44 (2.70 +/- 1.84 and 8.57 +/- 2.37,
      respectively), and 51 (2.09 +/- 1.41 and 7.49 +/- 2.60, respectively) (P <0.05).
      The quantification of fibroblast-like cells showed no significant difference (P
      >0.05) in the intragroup analysis of control and nicotine throughout experimental
      periods. In the intergroup analysis, group N had reduced proliferating cell
      nuclear antigen-positive fibroblasts compared to group C in all periods (P
      <0.05). CONCLUSION: The daily systemic administration of nicotine negatively
      affected, in vivo, the number and proliferation of fibroblast-like cells in the
      gingival tissue of rats.

PMID- 21189083
TI  - Efficacy of structurally diverse aldose reductase inhibitors on experimental
      periodontitis in rats.
AB  - BACKGROUND: To study aldose reductase and the sorbitol pathway in periodontitis
      and diabetes, rats with experimental periodontitis with or without diabetes were
      treated with three structurally diverse aldose reductase inhibitors (ARIs).
      METHODS: Periodontitis was induced with three consecutive palatal injections of
      Porphyromonas gingivalis lipopolysaccharide (LPS) at 48-hour intervals between
      the first and second molars on the right side in young, age-matched,
      streptozotocin-induced rats with and without diabetes 44 days after initiation of
      diets with and without the ARIs tolrestat, imirestat, and quercetin. As an
      internal control, phosphate-buffered saline (PBS) was similarly injected on the
      left side. Twenty-four days after the final injection, all rats were euthanized.
      Defleshed samples were stained with 5% toluidine blue and palatal digital images
      were traced to include the enamel crown and exposed root. The root/enamel ratios
      (to estimate alveolar bone loss) were analyzed with repeated measures analysis of
      variance. RESULTS: LPS injections resulted in significantly more bone loss versus
      PBS injections in both the rats with and without diabetes on normal diets (P
      <0.0001). All three ARIs significantly reduced LPS-induced periodontitis in the
      animals with and without diabetes (P <=0.003) to the level where they were not
      different from PBS-injected sites in normal diet controls. CONCLUSION: All ARIs
      demonstrated efficacy in preventing alveolar bone loss because of periodontitis
      in both animals with and without diabetes, suggesting a role for the sorbitol
      pathway and the potential for ARIs to reduce inflammatory responses downstream
      from aldose reductase.

PMID- 21189084
TI  - Bone morphogenetic protein-7 modifies the effects of insulin-like growth factors
      and intermittent parathyroid hormone (1-34) on human periodontal ligament cell
      physiology in vitro.
AB  - BACKGROUND: Components of the insulin-like growth factor (IGF) system and
      intermittent parathyroid hormone (PTH) were demonstrated to exert anabolic
      effects on the periodontal ligament (PDL) and, thereby, contribute to the
      regeneration of structures that were lost because of inflammatory periodontal
      disease. METHODS: In the present study, a PDL cell culture is created to examine
      whether a combination of IGFs and intermittent PTH would enhance the cellular
      response elicited by each factor alone and addressed the question of whether a
      pretreatment of the cells with bone morphogenetic protein (BMP)-7 alters the PDL
      cell phenotype and behavior on IGF-PTH stimulation. RESULTS: IGF-I and IGF-II
      enhanced proliferation and differentiation in preconfluent and confluent
      cultures. A BMP-7 pretreatment inhibited those effects in preconfluent cells but
      not in confluent cultures. Intermittent PTH (1-34) inhibited the proliferation
      but stimulated the differentiation of preconfluent cells, whereas the opposite
      effect was observed in confluent cultures. BMP-7 prestimulation made preconfluent
      cells respond like confluent cultures on intermittent PTH (1-34) challenge. A
      combined administration of PTH (1-34) and IGF-I or IGF-II mostly mirrored the
      effects seen for one of the individual agents alone, but synergistic effects were
      not observed. CONCLUSIONS: The present data indicate that both PTH (1-34) and IGF
      I or IGF-II exert a maturation stage-dependent effect on PDL cell proliferation
      and differentiation. Combining PTH (1-34) and IGF does not seem to potentiate the
      effects seen for the agents alone. Furthermore, our data suggest that BMP-7
      induces preconfluent cells to acquire a more differentiated phenotype and to
      respond to intermittent PTH (1-34) accordingly. Confluent cultures seem to be
      less susceptible to BMP-7.

PMID- 21189085
TI  - Chronic periodontitis and C-reactive protein levels.
AB  - BACKGROUND: This study aims to analyze the relationship between chronic
      periodontitis and C-reactive protein (CRP) by considering associated variables in
      individuals with or without cardiovascular disease. METHODS: A sample of 359
      individuals of both sexes (aged >=40 years) was assessed. Among these
      individuals, 144 subjects were admitted to the hospital because of a first
      occurrence of acute myocardial infarction; 80 subjects were in the hospital for
      reasons other than acute myocardial infarction; and 135 subjects were living in
      the community. A questionnaire was applied to obtain demographic and lifestyle
      characteristics. Complete clinical periodontal examinations and anthropometric
      assessments were performed. CRP levels, plasma glucose levels, lipid profiles,
      and blood tests were performed to investigate any conditions that might have
      suggested infection and/or inflammation. CRP evaluations were performed using
      nephelometry. Individuals were considered to have periodontal disease if they
      simultaneously presented at least four teeth with one or more sites with probing
      depth >=4 mm, clinical attachment loss >=3 mm, and bleeding on probing.
      Procedures for descriptive analyses and logistic regression were used. RESULTS:
      In the chronic periodontitis group, mean CRP levels were higher than those in the
      group without chronic periodontitis (2.6 +/- 2.6 mg/L versus 1.78 +/- 2.7 mg/L,
      respectively). The final model showed that individuals with chronic periodontitis
      were more likely to have high CRP levels (adjusted odds ratio: 2.26; 95%
      confidence interval: 1.30 to 3.93) considering the effects of age, schooling
      level, sex, smoking, high-density lipoprotein cholesterol, and diabetes.
      CONCLUSION: In this study, chronic periodontitis is associated with elevated
      plasma CRP levels, even after controlling for several potential confounders.

PMID- 21189086
TI  - Fimbriae of Porphyromonas gingivalis are important for initial invasion of
      osteoblasts, but not for inhibition of their differentiation and mineralization.
AB  - BACKGROUND: Porphyromonas gingivalis is etiologically associated with chronic
      periodontitis. The major fimbriae of this periodontal pathogen mediate binding to
      host gingival epithelial cells and fibroblasts, a critical function in the
      initiation of periodontitis. However, the role of fimbriae in P. gingivalis
      osteoblast interactions remains unknown. In the present study, the involvement of
      major fimbriae in the initial and long-term interactions between P. gingivalis
      and osteoblasts is investigated. METHODS: Primary mouse calvarial osteoblast
      cultures were established and inoculated with P. gingivalis ATCC 33277 or YPF1, a
      major fimbriae-deficient mutant of P. gingivalis. Confocal microscopy images were
      acquired to assess bacterial invasion. DNA content measurement, real-time
      polymerase chain reaction, and alizarin red S staining and calcium content
      analysis were used to study the impact of bacteria on the proliferation,
      differentiation, and mineralization of osteoblasts, respectively. RESULTS:
      Compared to the parent strain, YPF1 was significantly reduced in invasion of
      osteoblasts after 3 hours interaction. However, extended culture of infected
      osteoblasts did not reveal significant differences in persistence between the two
      strains. Proliferation of osteoblasts was not affected by either strain, and
      differentiation and mineralization of osteoblasts were inhibited by both strains
      to comparable levels. CONCLUSION: This study reveals that major fimbriae are
      involved in the initial invasion of osteoblasts by P. gingivalis, but are not
      essential for the subsequent inhibition of osteoblast differentiation and
      mineralization in long-term culture.

PMID- 21189087
TI  - Real-time quantitative polymerase chain reaction analysis of patients with
      refractory chronic periodontitis.
AB  - BACKGROUND: Periodontitis is a complex multifactorial disease and is typically
      polygenic in origin. Genes play a fundamental part in each biologic process
      forming complex networks of interactions. However, only some genes have a high
      number of interactions with other genes in the network and may, therefore, be
      considered to play an important role. In a preliminary bioinformatic analysis,
      five genes that showed a higher number of interactions were identified and termed
      leader genes. In the present study, we use real-time quantitative polymerase
      chain reaction (PCR) technology to evaluate the expression levels of leader genes
      in the leukocytes of 10 patients with refractory chronic periodontitis and
      compare the expression levels with those of the same genes in 24 healthy
      patients. METHODS: Blood was collected from 24 healthy human subjects and 10
      patients with refractory chronic periodontitis and placed into heparinized blood
      collection tubes by personnel trained in phlebotomy using a sterile technique.
      Blood leukocyte cells were immediately lysed by using a kit for total RNA
      purification from human whole blood. Complementary DNA (cDNA) synthesis was
      obtained from total RNA and then real-time quantitative PCR was performed. PCR
      efficiencies were calculated with a relative standard curve derived from a five
      cDNA dilution series in triplicate that gave regression coefficients >0.98 and
      efficiencies >96%. The standard curves were obtained using glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) and growth factor receptor binding protein 2
      (GRB2), casitas B-lineage lymphoma (CBL), nuclear factor-KB1 (NFKB1), and REL-A
      (gene for transcription factor p65) gene primers and amplified with 1.6, 8, 40,
      200, and 1,000 ng/MUL total cDNA. Curves obtained for each sample showed a linear
      relationship between RNA concentrations and the cycle threshold value of real
      time quantitative PCR for all genes. Data were expressed as mean +/- SE (SEM).
      The groups were compared to the analysis of variance. A probability value <0.01
      was considered statistically significant. RESULTS: The present study agrees with
      the preliminary bioinformatics analysis. In our experiments, the association of
      pathology with the genes was statistically significant for GRB2 and CBL (P
      <0.01), and it was not statistically significant for REL-A and NFKB1. CONCLUSION:
      This article lends support to our preliminary hypothesis that assigned an
      important role in refractory aggressive periodontitis to leader genes.

PMID- 21189088
TI  - The effects of Er:YAG laser treatment on titanium surface profile and
      osteoblastic cell activity: an in vitro study.
AB  - BACKGROUND: Laser light has been proposed as a tool to decontaminate the surface
      of endosseous implants. The effects of this maneuver on the interactions between
      cells and surface, however, are poorly known. The goal of the present study is to
      investigate osteoblast growth and differentiation on three commercially available
      surfaces untreated or after irradiation by erbium-doped:yttrium, aluminum, and
      garnet (Er:YAG) laser at two levels: 150 and 200 mJ/pulse at 10 Hz. METHODS:
      Human osteoblastic Saos-2 cells were plated on machined, sandblasted and acid
      etched titanium, or titanium plasma-sprayed disks. The effects of lasing were
      observed with a scanning electronic microscope, and cell viability was measured
      by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Moreover,
      we measured the production of the osteoblast-specific protein osteocalcin and of
      osteoprotegerin in the supernatants by immunoenzymatic assays. RESULTS: Although
      no visible changes were observed on machined or titanium plasma-sprayed disk
      samples at the tested levels, titanium peaks on sandblasted and acid-etched
      titanium disks appeared fused as a consequence of laser irradiation.
      Interestingly, cell proliferation was slower on irradiated titanium at both
      intensities on all the surfaces. Cell differentiation, as assessed by osteocalcin
      production, was generally unaffected by laser treatment, whereas the production
      of osteoprotegerin was decreased on all the surfaces irradiated at the intensity
      of 200 mJ/10Hz. CONCLUSIONS: These results indicate that Er:YAG laser at energy
      levels used in this study can alter the surface profile of titanium implants and
      these changes may negatively affect the viability and the activity of
      osteoblastic cells. Therefore, Er:YAG lasers should be used with caution on
      titanium surfaces.

PMID- 21189089
TI  - Effect of bisphosphonates on anodized and heat-treated titanium surfaces: an
      animal experimental study.
AB  - BACKGROUND: Recent investigations reported that osseointegration of titanium
      implants can be significantly reinforced with a nanostructure treated with anodic
      oxidation and heat treatment. This experimental study investigates the effect of
      bisphosphonates on the nanotubular implant surface in rats. METHODS: Thirty-six
      titanium implants were divided into three groups: 1) machine-turned (MT), 2)
      anodized and heat-treated (AH), and 3) anodized and heat- and bisphosphonate
      treated (AHB) groups. The 36 implants were randomly placed in both tibias of 18
      male Wistar rats. After 2 and 4 weeks, the levels of osseointegration of the
      implants were evaluated by a removal torque test and microcomputerized tomography
      (MUCT). Peri-implant bone tissue on the extracted region was examined for the
      expression of type I collagen and osteocalcin. RESULTS: The AHB group showed the
      highest removal torque at 2 and 4 weeks (13.92 +/- 1.51 Ncm and 18.10 +/- 2.15
      Ncm, respectively) followed, in order, by the AH group (11.63 +/- 1.58 Ncm at 2
      weeks and 14.80 +/- 2.34 Ncm at 4 weeks) and MT group (4.30 +/- 0.76 Ncm at 2
      weeks and 6.20 +/- 1.33 Ncm at 4 weeks) with statistically significant
      differences between the MT and other two groups at both time points. MUCT images
      also revealed a denser appearance around implants in the AHB group than in the
      other groups. Levels of type I collagen and osteocalcin expression were similar
      between the MT and AH groups; however, the values were significantly higher in
      the AHB group compared to the other groups, which were 220.85% +/- 71.09% and
      363.04% +/- 100.21%, respectively (P <0.05). CONCLUSION: Within the limits of
      this experiment, it was concluded that surface loading with bisphosphonates
      significantly improved the degree of osseointegration of titanium implants with a
      nanostructure.

PMID- 21189090
TI  - Is platelet concentrate advantageous for the surgical treatment of periodontal
      diseases? A systematic review and meta-analysis.
AB  - BACKGROUND: The aim of the present review is to systematically evaluate the
      effects of autogenous platelet concentrates on clinical outcomes of the surgical
      treatment of periodontal diseases. METHODS: MEDLINE, EMBASE, and the Cochrane
      Central Register of Controlled Trials were searched using a combination of
      specific search terms. Furthermore, a hand search of relevant journals and
      bibliographies of reviews was performed. Only randomized clinical trials were
      included. For periodontal intrabony defects, the primary outcome variable was the
      clinical attachment level. For gingival recession, outcome variables were root
      coverage and keratinized tissue increase. Data were adjusted for baseline values.
      The methodologic quality of the included studies was assessed. The results of
      studies in which the only difference between test and control groups was the
      adjunct of platelet concentrates were aggregated using a meta-analysis. For
      intrabony defects, the influences of guided tissue regeneration (GTR) and study
      type (split-mouth versus parallel studies) were also evaluated. RESULTS: The
      initial search yielded 424 studies. Of the 29 eligible studies, 24 studies were
      included. There were 16 studies on the treatment of periodontal intrabony
      defects, all of which used platelet-rich plasma (PRP); six studies on gingival
      recession treatment; and two studies on the treatment of furcation defects. A
      significant positive effect of the adjunct of PRP was found for intrabony
      defects. Such an effect was magnified in studies in which GTR was not used,
      whereas in studies using GTR, the use of PRP had no adjunctive effect. No effect
      of the study type was found. No significant effect of platelet concentrates was
      found for gingival recession treatment in which only studies with a follow-up <=6
      months displayed positive results. No significant benefit of PRP could be
      demonstrated for furcation treatment. CONCLUSIONS: PRP may exert a positive
      adjunctive effect when used in combination with graft materials, but not with
      GTR, for the treatment of intrabony defects. No significant benefit of platelet
      concentrates was found for the treatment of gingival recession.

PMID- 21189091
TI  - Magnitude and direction of mechanical stress at the osseointegrated interface of
      the microthread implant.
AB  - BACKGROUND: The mechanism by which the microthread implant preserves peri-implant
      crestal bone is not known. The objective of this research is to assess the effect
      of microthreads on the magnitude and direction of the stress at the bone-implant
      interface using finite element analysis modeling. METHODS: Three-dimensional
      finite element models representing the microthreaded implant (microthread model)
      and smooth surface implant (smooth model) installed in the mandibular premolar
      region were created based on microscopic and computed tomography images. The mesh
      size was determined based on convergence tests. Average maximum bite force of
      adults was used with four loading angles on the occlusal surface of the
      prosthesis. RESULTS: Regardless of the loading angle, principal stresses at the
      bone-implant interface of the microthread model were always perpendicular to the
      lower flank of each microthread. In the smooth model, stresses were affected by
      the loading angle and directed obliquely to the smooth interface, resulting in
      higher shear stress. The interfacial stresses decreased gradually in the apical
      direction in both models but with wavy pattern in the microthread model and
      smooth curve for the smooth model. Although peak principal stress values were
      higher around the microthread implant, peri-implant bone volume exhibiting a high
      strain level >4,000 MU was smaller around the microthread implant compared to the
      smooth implant. CONCLUSION: Stress-transferring mechanism at the bone-implant
      interface characterized by the direction and profile of interfacial stresses,
      which leads to more compressive and less shear stress, may clarify the
      biomechanical aspect of microthread dental implants.

PMID- 21189092
TI  - Predictive value of plasma galectin-3 levels in heart failure with reduced and
      preserved ejection fraction.
AB  - AIMS: galectin-3 is an emerging biomarker which has been studied in relatively
      small heart failure (HF) cohorts with predominantly systolic HF. We studied the
      prognostic value of base-line galectin-3 in a large HF cohort, with preserved and
      reduced left ventricular ejection fraction (LVEF), and compared this to other
      biomarkers. METHODS: we studied 592 HF patients who had been hospitalized for HF
      and were followed for 18 months. The primary end-point was a composite of all
      cause mortality and HF hospitalization. RESULTS: a doubling of galectin-3 levels
      was associated with a hazard ratio (HR) of 1.97 (1.62-2.42) for the primary
      outcome (P < 0.001). After correction for age, gender, BNP, eGFR, and diabetes
      the HR was 1.38 (1.07-1.78; P = 0.015). Galectin-3 levels were correlated with
      higher IL-6 and CRP levels (P < 0.002). Changes of galectin-3 levels after 6
      months did not add prognostic information to the base-line value (n = 291);
      however, combining plasma galectin-3 and BNP levels increased prognostic value
      over either biomarker alone (ROC analysis, P < 0.05). The predictive value of
      galectin-3 was stronger in patients with preserved LVEF (n = 114) compared to
      patients with reduced LVEF (P < 0.001). CONCLUSIONS: galectin-3 is an independent
      marker for outcome in HF and appears to be particularly useful in HF patients
      with preserved LVEF.

PMID- 21189093
TI  - Negative capsule endoscopy for obscure gastrointestinal bleeding is closely
      associated with the use of low-dose aspirin.
AB  - OBJECTIVE: Capsule endoscopy (CE) is used widely for determining the cause of
      obscure gastrointestinal bleeding (OGIB). However, negative findings still arise
      from CE examination. The aim of this study was to determine the factors
      associated with negative findings on CE in patients with OGIB. MATERIAL AND
      METHODS: A total of 134 patients who underwent CE for overt (n = 104) or occult
      (n = 30) OGIB between October 2007 and April 2010 were included. The clinical
      backgrounds of the patients (age; sex; the use of anti-coagulant, anti-platelet
      drugs or NSAIDs; comorbidity and the timing of CE examination after bleeding)
      were noted. RESULTS: The overall diagnostic yield of CE in detecting the relevant
      findings was 50% (n = 67). Multivariate analysis revealed that the use of anti
      platelet drug and the timing of CE (>= 16 days) were predictive factors for
      negative findings on CE (odds ratio 2.69 [1.01-7.21], p = 0.048 and odds ratio
      2.32 [1.01-5.33], p = 0.047, respectively). Among the patients with the use of
      low-dose aspirin (LDA, n = 28) as anti-platelet drug, cessation of it before CE
      was the only predictive factor for negative findings on CE (odds ratio 12.0 [1.72
      83.5], p = 0.012). CONCLUSION: In the patients with OGIB, the use of LDA and the
      cessation of it before CE made it difficult to detect the cause of bleeding by
      CE. This might indicate that the source of OGIB related to LDA heals immediately
      after cessation of the drugs or is a very small lesion that could not be detected
      by CE.

PMID- 21189094
TI  - "Pelvic radiation disease": new understanding and new solutions for a new disease
      in the era of cancer survivorship.
AB  - BACKGROUND: Cancer therapies increasingly achieve cure, but result in chronic
      moderate or severe gastrointestinal side effects in millions of patients
      worldwide. Paradoxically, modern therapies threaten to increase the burden of
      chronic gastrointestinal toxicity, not reduce it. AIM: To define pelvic radiation
      disease. METHODS: A reinterpretation of published data. RESULTS: The lack of
      interest in patients with pelvic radiation disease is startling. Symptoms after
      radiotherapy are only a manifestation of new onset gastrointestinal physiological
      deficits induced by the radiotherapy. With proper diagnosis and treatment of
      these deficit(s), the symptoms are curable. Science suggests that much
      radiotherapy-induced gastrointestinal morbidity is preventable. Once the true
      nature of radiation injury is understood, straightforward solutions emerge and
      inaccurate dogmas can be discarded. Imprecise language is a fundamental barrier
      to progress in complex disorders. CONCLUSIONS: Radiation-induced gastrointestinal
      toxicity is bedeviled by inappropriate terminology, causing confusion, and myth
      which legitimizes inappropriate clinical behavior. We must address honestly the
      uncomfortable reality that doctors, sometimes do harm. Not to do so in an era
      where survivorship is a reality, will deny millions often with severe symptoms
      from "pelvic radiation disease", the care which will help them.

PMID- 21189095
TI  - No excess surgical blood loss in patients with acquired type 2A von Willebrand
      disease.
AB  - OBJECTIVES: Acquired type 2A von Willebrand disease may develop as a consequence
      of aortic valve stenosis and is associated with varying degrees of bleeding
      tendency. It remains unknown, whether it portends excess blood loss during aortic
      valve replacement. DESIGN: We consecutively enrolled 45 patients with severe
      aortic valve stenosis undergoing aortic valve replacement. Patients with acquired
      type 2A von Willebrand disease were identified measuring the von Willebrand
      factor high molecular weight multimer. Data on the intraoperative, early
      postoperative, and the total blood loss within 24 hours of surgery was obtained
      and compared between groups. RESULTS: Acquired type 2A von Willebrand disease was
      found in 33% (n = 15/45) of the patients. Baseline characteristics were similar
      between groups. Patients with acquired type 2A von Willebrand disease neither had
      excess median intraoperative blood loss (375 ml (interquartile range 100-450 ml)
      vs. 350 ml (interquartile range 250-500 ml), p = 0.59) nor increased median total
      blood loss (695 ml (interquartile range 450-850 ml) vs. 752 ml (interquartile
      range 575-1035 ml), p = 0.41) as compared to patients without acquired type 2A
      von Willebrand disease. CONCLUSION: Acquired type 2A von Willebrand disease was
      not associated with increased blood loss during aortic valve replacement in
      patients with severe aortic valve stenosis.

PMID- 21189096
TI  - Efficacy of mobile telephone contact for follow-up in injecting heroin users.
AB  - BACKGROUND: Prospective follow-up of heroin users is known to be difficult due to
      their unstable lifestyle, and high follow-up rates have usually demanded major
      tracking efforts. In Sweden, mobile telephones are commonly used by heavy drug
      users for drug trading. OBJECTIVES: This methodology study aims to examine the
      efficacy of mobile telephone contact for prospective follow-up interviews with
      injecting heroin users recruited at the syringe exchange program of Malmo,
      Sweden. METHODS: Seventy-eight heroin users with mobile telephone numbers were
      included. Subjects reported using heroin for 28 days of the previous 30 days, and
      only 8% reported they had recently been engaged in work or studies. Clients were
      contacted between 15 and 21 times over 2 years, with each contact attempt
      generally involving two telephone calls on consecutive days. RESULTS: During
      follow-up, 68% of subjects had been successfully contacted for at least one
      follow-up interview (on average 6.9 interviews), and 25% of follow-up attempts
      were successful. In 23% of the sample (n=18), at least 50% of follow-up attempts
      were successful, and these subjects tended to be older (p=.05) and more likely to
      be female (p=.07), whereas follow-up rates were unrelated to baseline heroin use.
      CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Despite limited effort, and despite the
      severe situation of intravenous heroin users, mobile telephone contact can be
      used with heavy drug users in the present setting.

PMID- 21189097
TI  - Management of severe tibial bony defects with double metal blocks in knee
      arthroplasty-a technical note involving 9 cases.

PMID- 21189098
TI  - Increasing incidence of hip arthroplasty for primary osteoarthritis in 30- to 59
      year-old patients.
AB  - BACKGROUND AND PURPOSE: The use of hip arthroplasties is evidently increasing,
      but there are few published data on the incidence in young patients. METHODS: We
      used data on total and resurfacing hip arthroplasties (THAs and RHAs) from the
      Finnish Arthroplasty Register and population data from Statistics Finland to
      analyze the incidences of THA and RHA in patients aged 30-59 years in Finland,
      for the period 1980 through 2007. RESULTS: The combined incidences of THAs and
      RHAs among 30- to 59-year-old inhabitants increased from 9.5 per 10(5)
      inhabitants in 1980 to 61 per 10(5) inhabitants in 2007. Initially, the incidence
      of THA was higher in women than men, but since the mid-90s the incidences were
      similar. The incidence increased in all age groups studied (30-39, 40-49, and 50
      59 years) but the increase was 6-fold and 36-fold higher in the latter two groups
      than in the first. The incidence of THA was constant; the increased incidence of
      overall hip arthroplasty was due to the increasing number of RHAs performed.
      INTERPRETATION: We have found a steady increase in the incidence of hip
      arthroplasty in patients with primary hip osteoarthritis in Finland, with an
      accelerating trend in the past decade, due to an increase in the incidence of
      RHA. As the incidence of hip osteoarthritis has not increased, the indications
      for hip arthroplasty appear to have become broader.

PMID- 21189100
TI  - The rate of screw misplacement in segmental pedicle screw fixation in adolescent
      idiopathic scoliosis.
AB  - BACKGROUND AND PURPOSE: There are no reports in the literature on the influence
      of learning on the pedicle screw insertion. We studied the effect of learning on
      the rate of screw misplacement in patients with adolescent idiopathic scoliosis
      treated with segmental pedicle screw fixation. METHOD: We retrospectively
      evaluated low-dose spine computed tomography of 116 consecutive patients (aged 16
      (12-24) years, 94 females) who were operated during 4 periods over 2005-2009
      (group 1: patients operated autumn 2005-2006; group 2: 2007; group 3: 2008; and
      group 4: 2009). 5 types of misplacement were recorded: medial cortical
      perforation, lateral cortical perforation, anterior cortical perforation of the
      vertebral body, endplate perforation, and perforation of the neural foramen.
      RESULTS: 2,201 pedicle screws were evaluated, with an average of 19 screws per
      patient. The rate of screw misplacement for the whole study was 14%. The rate of
      lateral and medial cortical perforation was 7% and 5%. There was an inverse
      correlation between the occurrence of misplacement and the patient number, i.e.
      the date of operation (r = -0.35; p < 0.001). The skillfulness of screw insertion
      improved with reduction of the rate of screw misplacement from 20% in 2005-2006
      to 11% in 2009, with a breakpoint at the end of the first study period (34
      patients). INTERPRETATION: We found a substantial learning curve; cumulative
      experience may have contributed to continued reduction of misplacement rate.

PMID- 21189099
TI  - Infectiological, functional, and radiographic outcome after revision for
      prosthetic hip infection according to a strict algorithm.
AB  - BACKGROUND AND PURPOSE: Successful treatment of prosthetic hip joint infection
      (PI) means elimination of infection and restored hip function. However,
      functional outcome is rarely studied. We analyzed the outcome of the strict use
      of a treatment algorithm for PI. PATIENTS AND METHODS: The study groups included
      22 hips with 1-stage exchange for PI (group 1), 22 matched hips revised for
      aseptic loosening (controls), and 50 hips with 2-stage exchange (group 2).
      Relapse of infection, Harris hip score (HHS), limping, use of crutches,
      reoperations, complications, and radiographic changes were compared between the
      groups. RESULTS: There was 1 relapse of infection, which occurred in group 2. In
      group 1, the mean HHS was 84; 4 of 19 patients were limping and 2 required 2
      crutches, which was similar to the control results. In group 2, scores were lower
      and complication rates higher. The use of a Burch-Schneider ring and the presence
      of a deficient trochanter impaired function. There were no differences in
      radiographic outcome between the groups. INTERPRETATION: With the algorithm used,
      infection can be cured with high reliability. With a 1-stage procedure, mobility
      is maintained. After 2-stage procedures, function was impaired due to there being
      more previous surgery and more serious infection.

PMID- 21189101
TI  - "If I knew then what I know now": parents' reflections on raising a child with
      cerebral palsy.
AB  - In this study we investigated experiences of parents of children with cerebral
      palsy (CP) to identify areas in which health care providers and educators could
      improve practice. A second objective was to create educational material for
      parents of young children newly diagnosed with CP. A purposive sample of nine
      parents, who previously participated in the Adolescent Study of Quality of Life,
      Mobility, and Exercise, was recruited through phone. During an interview, parents
      reflected on the experience of raising a child with CP from birth to young
      adulthood. These interviews were audiotaped, transcribed, and coded using the
      International Classification of Functioning, Disability and Health-informed model
      and analyzed to identify major themes. Parents elaborated upon what was helpful
      and what could be changed to improve their children's and families' experiences
      through supports, advocacy, and education at different levels. The results
      informed the development of tips for parents and children with CP to enhance
      their families' experiences and interactions with health care providers,
      educators, and others.

PMID- 21189102
TI  - Relationships between fine-motor, visual-motor, and visual perception scores and
      handwriting legibility and speed.
AB  - Occupational therapists assess fine motor, visual motor, visual perception, and
      visual skill development, but knowledge of the relationships between scores on
      sensorimotor performance measures and handwriting legibility and speed is
      limited. Ninety-nine students in grades three to six with learning and/or
      behavior problems completed the Upper-Limb Speed and Dexterity Subtest of the
      Bruininks-Oseretsky Test of Motor Proficiency, the Beery-Buktenica Developmental
      Test of Visual-Motor Integration-5th Edition, the Test of Visual Perceptual
      Skills-Revised, the Visual Skills Appraisal, and a handwriting copying task.
      Correlations between sensorimotor performance scores and handwriting legibility
      varied from .07 to .38. Correlations between sensorimotor performance scores and
      handwriting speed varied from .04 to .42. Stepwise multiple regression analysis
      indicated that the variance in handwriting explained by these measures was <= 20%
      for legibility and <= 26% for speed. On the basis of multivariate analysis of
      variance only scores for the Developmental Test of Visual-Motor Integration
      differed between students classified as "skilled" and "unskilled" handwriters.
      The low magnitude of the correlations and variance explained by the sensorimotor
      performance measures supports the need for occupational therapists to consider
      additional factors that may impact handwriting of students with learning and/or
      behavior problems.

PMID- 21189104
TI  - Minor ailments in out-of-hours primary care: an observational study.
AB  - BACKGROUND: Many consultations are partly or totally spent on minor ailments. A
      minor ailment is defined as a health complaint which, by simple actions, patients
      could handle themselves. OBJECTIVE: To investigate the prevalence, type of
      conditions, and time spent on minor ailments in consultations in out-of-hours
      care in Norway. DESIGN AND SETTING: An observational study of consultations at
      six out-of-hours primary care centres was carried out during evenings and
      weekends in November and December 2008. Main outcome measures were number and
      type of minor ailments, as well as consultation time. The minor ailments were
      predefined by a list of conditions. Conditions which, by certain pre-set
      criteria, still needed a doctor's professional advice were reclassified as "no
      minor ailment". RESULTS: A total of 210 consultations were observed. The
      patients' mean age was 28 years (range 0-94). Cough, fever, sore throat, upper
      respiratory tract infection, and earache contributed 76% of the 211 minor
      ailments registered. After reclassification, 58 (28%) of the 210 consultations
      registered were classified as partly or totally a minor ailment. These minor
      ailments represented 18% of the doctors' total consultation time in the 210
      observed consultations. CONCLUSION: More than a quarter of the observed
      consultations were partly or totally spent on addressing minor ailments. This
      shows a potential for empowering patients to rely on self-care also for minor
      ailments in out-of-hours primary care.

PMID- 21189105
TI  - Sickness certification for patients with acute cough/LRTI in primary care in
      Poland and Norway.
AB  - OBJECTIVE: To compare the frequency and duration of sickness certificates issued
      by GPs to Polish and Norwegian working adults with acute cough/lower respiratory
      tract infection (LRTI). DESIGN: Cross-sectional observational study with
      clinicians from nine primary care centres in Poland and 11 primary care centres
      in Norway. GPs filled out a case report form for all patients, including
      information on antibiotic prescribing, sickness certification, and advice to stay
      off work. SETTING: Primary care research networks in Poland and Norway. SUBJECTS:
      Working adults with a new or worsening cough or clinical presentation suggestive
      of LRTI. MAIN OUTCOME MEASURES: Issuing sickness certificates and advising
      patients to stay off work. RESULTS: GPs recorded similar symptoms and signs in
      patients in the two countries. Antibiotics were prescribed more often in Polish
      than in Norwegian patients (70.4% vs. 27.1%, p < 0.0001). About half of the
      patients received a formal sickness certificate (50.5% in Norway and 52.0% in
      Poland). The proportion of patients advised to stay off work was significantly
      higher in the Polish sample compared with the Norwegian sample (75.2% vs. 56.1%,
      p = 0.002). Norwegian GPs less often issued sick certificates for more than seven
      days (5.6% vs. 36.9%, p < 0.0001). CONCLUSION: The overall proportion of sickness
      certification for acute cough/LRTI was similar in Norwegian and Polish patients.
      However, in the Polish sample, GPs more often advised patients to take time off
      work without issuing a sick note. When sickness certificates were issued,
      duration of longer than seven days was more common in Polish than in Norwegian
      patients.

PMID- 21189106
TI  - Evaluation of double vital staining with lugol's iodine and methylene blue in
      diagnosing superficial esophageal lesions.
AB  - OBJECTIVE: To evaluate the accuracy of double vital staining with lugol's iodine
      and methylene blue in the diagnosis of superficial esophageal lesions. METHODS:
      Doubtful superficial esophageal lesions identified with conventional endoscope
      were sprayed with 3% lugol's iodine and 0.5% methylene blue in order and observed
      in detail after each staining. Depending on the mucosal staining, biopsy specimen
      was obtained and underwent pathological examination. RESULTS: Using conventional
      endoscope, we found 356 lesions in 297 patients, among which 179 were esophageal
      squamous cell carcinoma and precancerous lesions (CAPs) (including 71 early
      esophageal squamous cell carcinoma, 23 esophageal high-grade intraepithelial
      neoplasias, 85 esophageal low-grade intraepithelial neoplasias) and 177 were non
      cancer non-precancerous lesions (NCNPs) (i.e. esophagitis and esophageal squamous
      cell hyperplasia). Most of CAPs were lightly stained or unstained, while NCNPs
      were hyperstained after lugol's iodine stained. The specificity, sensitivity,
      positive predictive value, negative predictive value and accuracy of lugol's
      lightly stained and unstained for identifying CAPs were 34.5%, 100%, 60.7%, 100%
      and 67.4%, respectively. Most of CAPs were lightly stained or hyperstained, while
      NCNPs were unstained after double vital staining. The specificity, sensitivity,
      positive predictive value, negative predictive value and accuracy of double vital
      staining lightly stained and hyperstained for identifying CAPs were 97.7%, 100%,
      97.8%, 100% and 98.9%, respectively. The accuracy of double vital staining for
      identifying CAPs was higher than that of lugol's iodine stained (p = 0.000).
      CONCLUSION: The double staining with lugol's iodine and methylene blue
      significantly improves the detection and diagnosis of early esophageal squamous
      cell CAPs.

PMID- 21189107
TI  - Have anxiety disorders been disowned by psychiatrists?
AB  - OBJECTIVE: The aim of this paper was to examine the place of anxiety disorders in
      contemporary psychiatry, its origins, and possible implications for the future of
      psychiatry. CONCLUSIONS: Several factors have led psychiatry away from neuroses
      and anxiety disorders and towards depression as a social paradigm of distress: a
      perception that anxiety disorders have relatively little relevance, the decline
      of psychoanalysis and rise of biological psychiatry, the downfall of the
      benzodiazepines and a failure to replace them with better anxiolytics, and the
      development of newer antidepressants. The subsequent imposition of the rigid
      conceptual dichotomy between depression and anxiety strengthened a notion that
      the focus of psychiatry should be on the 'depression side' of this divide. Having
      promoted cognitive-behavioural therapy as the best treatment for anxiety
      disorders, clinical psychologists have largely 'taken over' the anxiety disorders
      from psychiatrists. It is suggested that psychiatrists' surrender of the anxiety
      disorders may have negative consequences for the future of psychiatry.

PMID- 21189108
TI  - Pharmacological treatment of behavioural and psychological symptoms of dementia
      in psychogeriatric inpatient units.
AB  - OBJECTIVE: This study involved an examination of the current patterns of
      pharmacological treatment of patients with behavioural and psychological symptoms
      of dementia (BPSD) in psychogeriatric inpatient units. METHOD: An audit was
      conducted of discharge medications of patients with BPSD who were hospitalized at
      three separate inpatient units in Perth, Western Australia over a 1-year period.
      RESULTS: Prescribing patterns were found to be relatively similar across the
      three units. Dementia-specific drugs such as choline-esterase inhibitors and
      memantine comprised a minority of prescribed medication. Antipsychotics,
      benzodiazepines and sodium valproate were the most commonly prescribed drugs.
      Cyproterone acetate was used in a small number of patients at each of the three
      units. CONCLUSIONS: The broad range of medications used to treat BPSD, the
      relatively modest place of dementia-specific drugs in this patient group, and the
      co-prescribing of more than one psychotropic agent in the majority of patients
      support the prevailing impressions that BPSD are difficult to treat and that
      there is no consistently effective or superior medication or drug group.

PMID- 21189109
TI  - A prospective randomized study comparing electrochemically deposited
      hydroxyapatite and plasma-sprayed hydroxyapatite on titanium stems.
AB  - BACKGROUND AND PURPOSE: Plasma-sprayed hydroxyapatite (HA) is a successful
      coating for fixation of uncemented femoral stems. There may be alternative
      coatings with advantages in bone remodeling and transport of bone-active
      substances. We investigated whether an electrochemically deposited
      hydroxyapatite, Bonemaster (BM), might be a safe alternative in total hip
      arthroplasty. Our hypothesis was that the new coating would not be inferior to
      the conventional one. PATIENTS AND METHODS: 50 patients (55 hips) were included.
      The stem was tapered and porous-coated proximally. On top of the porous coating
      was either HA or BM. Patients were evaluated postoperatively and after 3, 6, 12,
      and 24 months to measure fixation by radiostereometric analysis (RSA), bone
      mineral density by dual-energy X-ray absorptiometry (DXA), and conventional
      radiography. Clinical evaluation was performed with Harris hip score and Oxford
      hip score, both preoperatively and after 2 years. RESULTS: After 2 years, the
      stems had subsided 0.25 (HA) and 0.28 (BM) mm and there were no statistically
      significant differences between the groups in any direction, regarding both
      migration and rotation. The BM group retained significantly more bone than the HA
      group in Gruen zone 1 during the first 2 years. The Harris and Oxford hip scores
      were similar in both groups. INTERPRETATION: Electrochemically deposited
      hydroxyapatite on an uncemented stem does not appear to be inferior to plasma
      sprayed HA regarding clinical and radiological results, bone remodeling, and
      micromotion after 2 years follow-up.

PMID- 21189110
TI  - Elevation of circulating HLA DR(+) CD8(+) T-cells and correlation with chromium
      and cobalt concentrations 6 years after metal-on-metal hip arthroplasty.
AB  - BACKGROUND AND PURPOSE: Following metal-on-metal hip arthroplasty (THA),
      immunological reactions including changes in lymphocyte populations, aseptic
      loosening, and lymphocytic pseudotumors occur. We hypothesized that changes in
      lymphocyte subpopulations would be associated with elevated metal ion
      concentrations. METHODS: A randomized trial involving 85 patients matched for age
      and sex and randomized to receiving metal-on-metal (n = 41) or metal-on
      polyethylene total hip arthroplasty (n = 44) was conducted. 36 patients were
      eligible for follow-up after mean 7 (6-8) years. Concentrations of chromium and
      cobalt were analyzed by high-resolution inductively coupled plasma mass
      spectrometry. Leukocyte subpopulations and immunoglobulins in patient blood were
      measured using standard laboratory methods. RESULTS: Patients with a metal-on
      metal hip had higher serum concentrations of chromium (1.05 vs. 0.36 MUg/L; p <
      0.001) and cobalt (0.86 vs. 0.24 MUg/L; p < 0.001) than those with metal-on
      polyethylene. The percentage of HLA DR(+) CD8(+) T-cells was higher in the metal
      on-metal group (10.6 vs. 6.7%; p = 0.03) and correlated positively with chromium
      and cobalt concentrations in patient blood (Pearson's correlation coefficient:
      0.39, p = 0.02; 0.36, p = 0.03, respectively). The percentage of B-cells was
      lower in the metal-on-metal group (p = 0.01). The two groups were similar with
      respect to immunoglobulin concentrations and Harris hip scores, and there were no
      radiographic signs of loosening. INTERPRETATION: We conclude that immunological
      alterations appear to be associated with increased cobalt and chromium
      concentrations. It is tempting to speculate that HLA DR(+) CD8(+) T-cells are
      involved in the pathogenesis of allergic reactions, implant loosening, and
      lymphocytic pseudotumors.

PMID- 21189111
TI  - Transposition of the apophysis of the greater trochanter for reconstruction of
      the femoral head after septic hip arthritis in children.
AB  - BACKGROUND AND PURPOSE: Total necrosis of the femoral head after infection in
      children during their first months of life gives a dislocated hip with severe leg
      shortening. A new femoral head can be achieved with subtrochanteric osteotomy and
      transposition of the apophysis of the greater trochanter into the acetabulum.
      Previous reports have dealt with short-term results (up to 12 years). Here I
      present some results of this procedure 15-24 years after operation. PATIENTS AND
      METHODS: 4 children aged 1-6 years with complete necrosis of the femoral head
      were operated on with transposition of the greater trochanter. Secondary shelf
      plasty was performed later in 1 child, distal femoral epiphysiodesis in another,
      and femoral bone lengthening in 1 child. The mean follow-up period was 19 (15-24)
      years. RESULTS: A new femoral head developed in all hips. 2 of them had a
      spherical head with a good acetabular cover, and without any osteoarthritis
      except for slight reduction of cartilage height. These hips were painless, with a
      mobility that allowed good walking function after 16 and 24 years, respectively.
      In the other 2 patients, in which there was a severe acetabular dysplasia at the
      primary operation, the new femoral head was somewhat flattened; painful
      osteoarthritis led to hip replacement 15 and 21 years after trochanter
      arthroplasty. Even these patients had a relatively good walking function until
      the last couple of years before hip replacement. Maximum leg length discrepancy
      was 7 cm. INTERPRETATION: Trochanter arthroplasty with subtrochanteric osteotomy
      in total femoral head necrosis after septic arthritis in children may give
      satisfactory long-term results provided adequate acetabular cover is obtained.
      Although the method cannot provide a normal hip, it can contribute to less length
      discrepancy, less pain, improved gait, and more favorable conditions for later
      hip replacement.

PMID- 21189112
TI  - Health-related quality of life (EQ-5D) before and after orthopedic surgery.
AB  - BACKGROUND AND PURPOSE: Population data on mortality and life expectancy are
      generally available for most countries. However, no longitudinal data based on
      the health-related quality of life outcome from the EQ-5D instrument have been
      reported for orthopedic patients. We assessed the effect of orthopedic surgery as
      measured by EQ-5D. METHODS: We analyzed EQ-5D data from 2,444 patients who were
      operated at the Department of Orthopedic Surgery at Karolinska University
      Hospital, 2001-2005. We also made a comparison between results from this cohort
      and those from a Swedish EQ-5D population survey. RESULTS: The mean EQ-5D (index)
      score improved from 0.54 to 0.72. Hip and knee arthroplasty, operations related
      to previous surgery, trauma-related procedures, and rheumatoid arthritis
      surgeries had preoperative EQ-5D (index) scores of 0.48 to 0.52. All of these
      groups showed substantial improvement in scores (0.63 to 0.80). Patients with
      tumors or diseases of the elbow/hand showed higher preoperative scores (0.66 to
      0.77), which were similar postoperatively. In most patients, the EQ-5D (index)
      score improved but did not reach the level reported for an age- and sex-matched
      population sample (mean difference = 0.11). INTERPRETATION: Our results can be
      used as part of the preoperative patient information to increase the level of
      patient awareness and cooperation, and to facilitate rehabilitation. In future it
      will be possible-but not easy-to use the EQ-5D instrument as a complementary
      consideration in clinical priority assessment.

PMID- 21189113
TI  - Would loss to follow-up bias the outcome evaluation of patients operated for
      degenerative disorders of the lumbar spine?
AB  - BACKGROUND AND PURPOSE: Loss to follow-up may bias the outcome assessments of
      clinical registries. In this study, we wanted to determine whether outcomes were
      different in responding and non-responding patients who were included in a
      clinical spine surgery registry, at two years of follow-up. In addition, we
      wanted to identify risk factors for failure to respond. METHODS: 633 patients who
      were operated for degenerative disorders of the lumbar spine were followed for 2
      years using a local clinical spine registry. Those who did not attend the clinic
      and those who did not answer a postal questionnaire-for whom 2 years of outcome
      data were missing-and who would be lost to follow-up according to the standard
      procedures of the registry protocols, were defined as non-respondents. They were
      traced and interviewed by telephone. Outcome measures were: improvement in health
      related quality of life (EQ-5D), leg pain, and back pain; and also general state
      of health, employment status, and perceived benefits of the operation. RESULTS:
      We found no statistically significant differences in outcome between respondents
      (78% of the patients) and non-respondents (22%). Receipt of postal questionnaires
      (not being summoned for a follow-up visit) was the strongest risk factor for
      failure to respond. Forgetfulness appeared to be an important cause. Older
      patients and those who had complications were more likely to respond.
      INTERPRETATION: A loss to follow-up of 22% would not bias conclusions about
      overall treatment effects and, importantly, there were no indications of worse
      outcomes in non-respondents.

PMID- 21189114
TI  - Asthma symptoms, lung function, and markers of oxidative stress and inflammation
      in children exposed to oil refinery pollution.
AB  - OBJECTIVES: Little is known about the effects of exposure to petroleum refinery
      emissions on respiratory health in children. We evaluated lung function and
      markers of inflammation and oxidative stress in children and adolescents with and
      without asthma or wheezing symptoms living in a petrochemical polluted area
      (Sarroch, Sardinia) versus a reference area (Burcei). METHODS: Parents of 275/300
      6- to 14-year-old children living in Sarroch and parents of 214/323 children
      living in Burcei answered a questionnaire on respiratory symptoms and risk
      factors. Measurements of forced expiratory volume after 1 second (FEV(1)) and of
      forced expiratory flow rates at 25-75% of vital capacity (FEF(25-75)) were
      available in 27 and 23 asthma/wheezing-positive subjects and in 7 and 54
      asthma/wheezing-negative subjects in Sarroch and in Burcei, respectively; for
      fractional exhaled nitric oxide (FE(NO)) corresponding figures were 27 and 24 and
      8 and 55 in Sarroch and in Burcei, respectively. Malondialdehyde-deoxyguanosine
      (MDA-dG) adduct levels in nasal mucosa were measured in 12- to 14-year-old
      adolescents (8 and 14 asthma/wheezing-positive and 20 and 28 asthma/wheezing
      negative subjects in Sarroch and in Burcei, respectively). Air pollutants were
      assessed during 3 weeks, starting 1 week before lung function, FE(NO), and MDA-dG
      measurements. Generalized linear models were used to estimate the effect of the
      area of residence adjusting for confounders. RESULTS: Weekly average
      concentrations of sulfur dioxide were 6.9-61.6 MUg/m(3) in Sarroch versus 0.3-7.6
      MUg/m(3) in the rural area of Burcei; of nitrogen dioxide, 5.2-28.7 MUg/m(3)
      versus 1.7-5.3 MUg/m(3); and of benzene, 1.8-9.0 MUg/m(3) versus 1.3-1.5
      MUg/m(3), respectively. Children living in Sarroch versus children living in the
      reference area showed an increase in wheezing symptoms {adjusted prevalence
      ratio=1.70 [90% confidence interval (CI)=1.01; 2.86]}; a decrease in lung
      function [variation in FEV(1)=-10.3% (90% CI=-15.0; -6.0%) and in FEF(25-75)=
      12.9% (90% CI=-20.7; -4.3%)]; an increase in bronchial inflammation [variation in
      FE(NO)=+35% (90% CI=11.7; 80.1%)]; and an increase in MDA-dG adducts of +83% (90%
      CI=22.9; 174.1%). CONCLUSIONS: Data from this small study are consistent with the
      role of environmental pollutants on lung function and inflammation.

PMID- 21189115
TI  - Musculoskeletal dysfunction and pain in adults with asthma.
AB  - BACKGROUND: The mechanical alterations related to the overload of respiratory
      muscles observed in adults with persistent asthma might lead to the development
      of chronic alterations in posture, musculoskeletal dysfunction and pain; however,
      these changes remain poorly understood. OBJECTIVE: This study aimed to assess
      postural alignment, muscle shortening and chronic pain in adults with persistent
      asthma. METHODS: This cross-sectional and controlled study enrolled 30 patients
      with mild (n = 17) and severe (n = 13) persistent asthma. Fifteen non-asthmatic
      volunteers were also assessed. Asthma was classified by the Global Initiative for
      Asthma (GINA) guidelines. Postural alignment and muscle shortening were evaluated
      by head and shoulder positions, chest wall mobility, and posterior (trunk and
      lower limb) muscle flexibility. In addition, the measures used were previously
      tested for their reproducibility. Pain complaints were also assessed. RESULTS: In
      comparison with non-asthmatic subjects, patients with mild or severe persistent
      asthma held their head and shoulders more forward and had lower chest wall
      expansion, decreased shoulder internal rotation, and decreased thoracic spine
      flexibility. Chronic lower thoracic, cervical, and shoulder pain was
      significantly increased in patients with mild or severe asthma compared with non
      asthmatic subjects (p < 0.05). CONCLUSION: Adults with persistent asthma have
      musculoskeletal dysfunction and chronic pain that is independent of the severity
      of their disease but that might be related to their age at the onset of disease
      symptoms.

PMID- 21189116
TI  - Cancer stem cells switch on tumor neovascularization.
AB  - Recent studies on cancer stem cells (CSCs), a special subpopulation of tumor
      cells, promote our understanding of tumorigenesis, neovascularization, invasion,
      drug resistance and tumor recurrence, which establishes new concepts for cancer
      diagnosis and treatment. Therefore, the biological features and behaviors of CSCs
      have become an exciting frontier of cancer research. CSCs initiate tumor
      neovascularization and promote invasion with yet to be defined mechanisms. In
      this review, we provide evidence for the role of CSCs in tumor vascularization
      and discuss the potential mechanisms and therapeutic significance based on the
      interaction between CSCs and their vascular niches.

PMID- 21189117
TI  - Heterogeneity amongst 5-HT3 receptor subunits: is this significant?
AB  - The serotonin 3 (5-HT3) receptor is a ligand gated ion channel unlike the other 5
      HT receptors which are G protein coupled receptors. The functional 5-HT3 receptor
      forms a pentamer of five symmetrically arranged subunits surrounding a central
      pore. The 5-HT(3A) subunit was first identified at a molecular level and can form
      functional homomers or heteromers with the 5-HT(3B) subunit. Recently, three new
      5-HT3 subunits have been discovered and these can also form functional heteromers
      with the 5-HT(3A) subunit. In addition, splice variants of the 5-HT3 subunits
      have also been reported. These findings have markedly increased the complexity of
      the 5-HT3 receptor and may form part of the explanation of unresolved differences
      between studies investigating 5-HT3 receptor function in cell lines compared with
      native tissues. In this review we discuss the properties of the different
      subunits and their distribution to determine if they contribute to functional
      changes in the 5-HT3 receptor. Several recent pharmacogenomic studies have
      revealed single nucleotide polymorphisms (SNPs) and other variations in the
      different 5-HT3 receptor subunits that are associated with various clinical
      conditions. We discuss the implications of these findings with respect to drug
      design and tailored pharmacogenomic therapies.

PMID- 21189118
TI  - Transforming growth factor-beta signaling in motor neuron diseases.
AB  - Transforming growth factor beta (TGF-beta), a pleiotropic cytokine, regulates a
      diverse range of cellular responses, such as proliferation, differentiation,
      migration, and apoptosis. The TGF-beta1, -beta2, and -beta3 isoforms are
      expressed by neurons and glial cells, and their receptors are expressed
      throughout the central nervous system. Several lines of evidence demonstrate that
      TGF-beta signaling protects neurons from glutamate-mediated excitotoxicity, a
      putative mechanism underlying the pathogenesis of various neurodegenerative
      disorders such as amyotrophic lateral sclerosis (ALS). Recent studies indicate
      that the TGF-beta-Smad2/3 pathway restores motor function in a mouse model of
      ALS, and that disruption of TGF-beta signaling due to the transcriptional
      dysregulation of its receptor is associated with polyglutamine-induced motor
      neuron damage in spinal and bulbar muscular atrophy. Moreover, the TGF-beta
      Smad2/3 pathway regulates the function of glial cells, although the implication
      of this regulation in neurodegeneration remains elusive. Conversely, myostatin, a
      member of the TGF-beta superfamily, has gained attention as a potential
      therapeutic target for neuromuscular disorders because genetic deletion of this
      factor results in increased muscle volume. Signal transduction by BMP, a member
      of the TGF-beta super family, regulates the function and growth of the
      neuromuscular junction, while the disruption of this signaling has been reported
      in animal models of hereditary spastic paraplegia. These findings support the
      hypothesis that the disruption of TGF-beta signaling is an important molecular
      event in the pathogenesis of motor neuron diseases, and that the modification of
      this signaling pathway represents a new therapeutic strategy against these
      devastating disorders.

PMID- 21189119
TI  - The molecular machinery regulating apoptosis signal transduction and its
      implication in human physiology and pathophysiologies.
AB  - The regulation of apoptotic cell death, a terminal and fatal cell fate decision,
      has been intensely investigated and, due to its paramount implications for human
      health and disease, has sparked one of the most prolific and competitive research
      fields in biological and biomedical sciences of the past decades. Many key
      components of the molecular machinery processing and transducing apoptotic cell
      death signals have been described in great detail by now, dramatically advancing
      our understanding of how the network of apoptosis signaling proteins integrates
      and regulates cell death signals, and ultimately executes apoptosis. Building on
      the latest significant advances in deciphering apoptosis signal transduction as
      well as on the central original groundbreaking discoveries in cell death
      research, we here present an in-depth description of the current knowledge on the
      core molecular machinery of apoptotic signaling and how it is implicated in human
      physiology and pathophysiologies.

PMID- 21189120
TI  - The dual role of interleukin-25 in the control of immune-mediated pathologies.
AB  - Interleukin-25 (IL-25) plays a key role in the initiation and expansion of T
      helper (Th) 2 cell-mediated immune responses, thereby contributing to allergic
      diseases and host defense against helminthic parasites. More recent studies have
      however shown that IL-25 can also control the function of non-T cells, such as
      antigen presenting cells and endothelial cells, and reduces Th1/Th17-mediated
      pathologies. These new and exciting observations reveal a broader role for IL-25
      than previously anticipated, and delineate various scenarios where therapeutic
      interventions around IL-25 activity can be imagined.

PMID- 21189121
TI  - Eicosanoids in prevention and management of diseases.
AB  - Eicosanoids, which originate from polyunsaturated fatty acids (PUFAs), have a
      major impact on homeostasis maintenance as secondary signal transducers. Signal
      cascade, which includes reception, processing and signal transduction coming from
      the environment into the cell, determines the type of response evoked. Signal
      distortion may take place on every level of this cascade and this in consequence
      could lead to the development of many diseases. Any intervention into PUFAs
      metabolism leads to quantitative and qualitative changes of synthesized
      eicosanoids. Some of them promote, whereas others inhibit carcinogenesis, some
      are pro- or anti-inflammatory and the overall result depends on the outcome of
      these contradictory effects. The type and amount of produced eicosanoids depends
      on substrates' availability and activity of enzymes catalyzing different stages
      of their transformation. A particularly negative role was assigned to the over
      expression of phospholipase A2, cyclooxygenase-2, 5- and 12-lipoxygenases, while
      the contribution of other oxygenases and their metabolites is considerably less
      clear. The information about their interplay is extremely sparse and inadequate
      to understand intricacies of the mechanisms involved. There are indications that
      utilization of selected eicosanoids (their analogs, agonists or antagonists)
      could be a better way of disease prevention and treatment, more effective than
      excessive dietary supplementation of fatty acids. This review presents a more
      global picture of oxygenases and their PUFA metabolites giving a brief summary of
      our current understanding of perspectives and pitfalls of their regulation and
      mediatory action in human diseases.

PMID- 21189122
TI  - Converging pathways in the occurrence of endoplasmic reticulum (ER) stress in
      Huntington's disease.
AB  - A variety of neurological diseases including Huntington's disease (HD),
      Alzheimer's disease and Parkinson's disease share common neuropathology,
      primarily featuring the presence of abnormal protein inclusions containing
      specific misfolded proteins. Mutations leading to expansion of a poly-glutamine
      track in Huntingtin cause HD, and trigger its misfolding and aggregation. Recent
      evidence indicates that alterations in the secretory pathway, in particular the
      endoplasmic reticulum (ER), are emerging features of HD. Although it is not clear
      how cytoplasmic/nuclear located mutant Huntingtin alters the function of the ER,
      several reports indicate that mutant Huntingtin affects many essential processes
      related to the secretory pathway, including inhibition of ER-associated
      degradation, altered ER/Golgi vesicular trafficking and axonal transport,
      disrupted autophagy and abnormal ER calcium homeostasis. All these alterations
      are predicted to have a common pathological outcome associated to disturbance of
      protein folding and maturation pathways at the ER, generating chronic ER stress
      and neuronal dysfunction. Here, we review recent evidence involving ER stress in
      HD pathogenesis and discuss possible therapeutic strategies to target organelle
      function in the context of disease.

PMID- 21189125
TI  - A closer look at the high affinity benzodiazepine binding site on GABAA
      receptors.
AB  - Ligands of the benzodiazepine binding site of the GABA(A) receptor come in three
      flavors: positive allosteric modulators, negative allosteric modulators and
      antagonists all of which can bind with high affinity. The GABA(A) receptor is a
      pentameric protein which forms a chloride selective ion channel and ligands of
      the benzodiazepine binding site stabilize three different conformations of this
      protein. Classical benzodiazepines exert a positive allosteric effect by
      increasing the apparent affinity of channel opening by the agonist gamma
      aminobutyric acid (GABA). We concentrate here on the major adult isoform, the
      alpha(1)beta(2)gamma(2) GABA(A) receptor. The classical binding pocket for
      benzodiazepines is located in a subunit cleft between &alpha;(1) and gamma(2)
      subunits in a position homologous to the agonist binding site for GABA that is
      located between beta(2) and alpha(1) subunits. We review here approaches to this
      picture. In particular, point mutations were performed in combination with
      subsequent analysis of the expressed mutant proteins using either
      electrophysiological techniques or radioactive ligand binding assays. The
      predictive power of these methods is assessed by comparing the results with the
      predictions that can be made on the basis of the recently published crystal
      structure of the acetylcholine binding protein that shows homology to the N
      terminal, extracellular domain of the GABA(A) receptor. In addition, we review an
      approach to the question of how the benzodiazepine ligands are positioned in
      their binding pocket. We also discuss a newly postulated modulatory site for
      benzodiazepines at the alpha(1)/beta(2) subunit interface, homologous to the
      classical benzodiazepine binding pocket.

PMID- 21189126
TI  - Quadruplex DNA: a promising drug target for the medicinal inorganic chemist.
AB  - Compounds that can bind to and stabilize quadruplex DNA structures in telomeres,
      or induce formation of such structures from ssDNA, represent an attractive
      general approach to the treatment of cancer. Until recently most effort in this
      area has been directed towards the synthesis of organic compounds for this
      purpose. More recently there has been growing recognition that metal complexes
      offer a number of potential advantages for the preparation of lead complexes that
      bind with high affinity and selectivity for quadruplex DNA. This review seeks to
      discuss the work that has been reported in this area to date. While most early
      studies focused on metal complexes of porphyrin ligands, during the past 4 years
      there has been a dramatic increase in the number of papers in the literature
      examining the potential of mononuclear complexes of a variety of other ligands,
      particularly Schiff base ligands and those based on phenanthroline, as quadruplex
      DNA binders and telomerase inhibitors. In addition, there has been growing
      interest in exploiting supramolecular chemistry to prepare novel multinuclear
      complexes that bind to this new drug target.

PMID- 21189127
TI  - Studies on the biotransformations and biodistributions of metal-containing drugs
      using X-ray absorption spectroscopy.
AB  - Most metal-based drugs are pro-drugs; therefore, it is essential that methods are
      developed to follow their speciation in biological fluids, cells and tissues.
      This will lead to both a better understanding of the factors that affect their
      efficacies and toxicities and, consequently, to the design of new and superior
      drugs. The use of X-ray absorption spectroscopy on bulk samples, and X-ray
      microprobe techniques on cells and tissues, provides unprecedented information on
      the biotransformations and biodistributions of metal-containing drugs that is
      required for a better understanding of their pharmacology. Here the methodologies
      that have been used on a range of metal- or metalloid-containing drugs and
      dietary supplements are reviewed, with an emphasis on research conducted within
      our group. In particular, applications of these techniques to anti-cancer, anti
      diabetic, and anti-inflammatory drugs are discussed.

PMID- 21189128
TI  - Reorganizing metals: the use of chelating compounds as potential therapies for
      metal-related neurodegenerative disease.
AB  - Metal ions, particularly copper, zinc and iron, are implicated in several
      amyloidogenic neurodegenerative disorders. In the brain, as elsewhere in the
      body, metal ion excess or deficiency can potentially inhibit protein function,
      interfere with correct protein folding or, in the case of iron or copper, promote
      oxidative stress. The involvement of metal ions in neurodegenerative disorders
      has made them an emerging target for therapeutic interventions. One approach has
      been to chelate and sequester the ions and thus limit their potential to
      interfere with protein folding or render them unable to undergo redox processes.
      Newer approaches suggest that redistributing metal ions has therapeutic benefits,
      and recent studies indicate that alleviating cellular copper deficiency may be a
      plausible way to limit neurodegeneration. In this review we discuss the role of
      metals in amyloidogenic, neurodegenerative disorders and highlight some
      mechanisms and compounds used in various therapeutic approaches.

PMID- 21189129
TI  - Peptide targeted copper-64 radiopharmaceuticals.
AB  - Peptide targeted 64Cu-labelled diagnostic agents for positron emission tomography
      are viable candidates for molecular imaging of cancer. In a clinical setting,
      optimal image quality relies on selective tumor uptake of the 64Cu-labelled
      radiotracer. The three components of the radiotracer construct--the chelate
      group, linker and targeting peptide--all influence the biodistribution of the
      64Cu-labelled radiotracer in vivo. Low or moderate Cu complex stability in vivo
      results in transmetallation of 64Cu to endogenous proteins, giving rise to high
      background activity. The length and the nature of the linker group affect the
      affinity of the 64Cu-labelled radiotracer for the target receptor. Variations in
      the peptide sequence can impact on the metabolic stability and therefore the
      bioavailability and tumor retention of the 64Cu-labelled radiotracer in vivo.
      Lastly, the hydrophilicity of the construct can influence radiotracer metabolism
      and clearance pathways. Recent advances in the field of peptide targeted 64Cu
      labelled radiopharmaceuticals involve GRPR-targeted and alphavbeta3 integrin
      receptor-targeted constructs. These constructs are based on the bombesin peptide
      sequence and the RGD recognition motif respectively. These examples are reviewed
      as case studies in the optimisation of 64Cu radiotracer design.

PMID- 21189130
TI  - Synthetic and natural products as iron chelators.
AB  - An evaluation of existing and proposed Fe chelators, both synthetic and natural
      products, for the treatment of Fe-overload disease must address a number of
      issues. There are fundamental parameters that determine the efficacy of a drug:
      absorption, distribution, metabolism, clearance and toxicity. However, the
      administration of chelator for Fe overload aims to generate Fe complexes in vivo
      that are able to be excreted. Hence, the chemical and pharmacological properties
      of the complexes formed are equally important as the chelators themselves. The
      redox properties of the Fe complexes formed is particularly relevant to their
      toxicity. If both Fe(II) and Fe(III) oxidation states of the complexes are
      biologically accessible, then there is potential for the auto-catalytic
      production of deleterious free radicals, by Fenton-type chemistry. In addition,
      since the burden of Fe overload disease falls predominantly on some of the
      poorest economies, the cost of a drug must be considered, as well as the mode of
      delivery. There are also possible issues with the use of naturally occurring
      ligands, which may form Fe complexes capable of being utilised by opportunistic
      bacteria. This review will concentrate on recent developments in our chemical
      understanding of existing chelators approved or proposed for use and will also
      consider some of the candidates from natural sources that have been recently
      proposed.

PMID- 21189131
TI  - Transition metal based anticancer drugs.
AB  - With an ageing baby-boomer population in the Western World, cancer is becoming a
      significant cause of death. The prevalence of cancer and all associated costs,
      both in human and financial terms, drives the search for new therapeutic drugs
      and treatments. Platinum anticancer agents, such as cisplatin have been highly
      successful but there are several disadvantages associated with their use. What is
      need are new compounds with different mechanisms of action and resistance
      profiles. What needs to be recognised is that there are many other metal in the
      periodic table with therapeutic potential. Here we have highlighted metal
      complexes with activity and have illustrate the different approaches to the
      design of anticancer complexes.

PMID- 21189132
TI  - ABC transporters: unvalidated therapeutic targets in cancer and the CNS.
AB  - The discovery of the multidrug transporter P-glycoprotein (Pgp) over 35 years ago
      in drug resistant cells prompted several decades of work attempting to overcome
      drug resistance by inhibition of drug efflux. Despite convincing laboratory data
      showing that drug transport can be inhibited in vitro, efforts to translate this
      discovery to the clinic have not succeeded. Since overexpression of Pgp and
      related transporters including ABCG2 and members of the ABCC family have been
      linked with poor outcome, it remains a reasonable hypothesis that this poor
      outcome is linked to reduction of drug exposure by efflux, and thus to drug
      resistance. In this review, we will discuss the question of whether ABC
      transporters mediate drug resistance in cancer through a reduction in drug
      accumulation in tumors, and whether the "Pgp inhibition hypothesis" might be
      wrong. The hypothesis, which holds that increased chemotherapy effectiveness can
      be achieved by inhibiting Pgp-mediated drug efflux has only been validated in
      model systems. Possible explanations for the failure to validate this clinically
      include the existence of other modulators of drug accumulation and uptake in
      tumors. Despite these difficulties, a potential role has emerged for drug
      transporters as therapeutic targets in the central nervous system (CNS). Both
      lines of investigation point to the need for imaging agents to facilitate the
      study of drug accumulation in human cancer. This is a critical need for targeted
      therapies where an important dose-response relationship is likely to exist, and
      where drug resistance renders many of the novel targeted agents ineffective in a
      subset of patients.

PMID- 21189133
TI  - Metabolism of benzodiazepine and non-benzodiazepine anxiolytic-hypnotic drugs: an
      analytical point of view.
AB  - A review with 132 references. Several kinds of anxiolytic and hypnotic drugs are
      currently available on the market. Although BZDs are surely the most frequently
      prescribed among them, several chemically unrelated compounds have been
      commercialised, which can provide similar or even higher efficacy and
      tolerability. These drugs can prove useful for patients who are non-responder or
      intolerant to benzodiazepine treatment, thus giving broader therapeutic options
      to the clinician. The most important studies on the metabolic characteristics of
      several non-benzodiazepine anxiolytics and hypnotics are reported and briefly
      discussed in this review; moreover, the analytical methods related to these
      studies are also described and commented upon and their characteristics are
      highlighted. Finally, an update is included on recent (2007-2010) metabolism and
      pharmacokinetic studies on benzodiazepines. A monograph is included for each of
      the following drugs: zolpidem, zaleplon, zopiclone, ramelteon, buspirone and
      tandospirone; updates are included for the following benzodiazepines: alprazolam,
      bromazepam, diazepam, flunitrazepam, lorazepam, midazolam, oxazepam and
      triazolam.

PMID- 21189134
TI  - Current in vitro high throughput screening approaches to assess nuclear receptor
      activation.
AB  - The screening of new drug candidates for nuclear receptor activation can identify
      agents with the potential to produce drug-drug interactions or elicit adverse
      drug effects. The nuclear receptors of interest are those that control the
      expression of drug metabolizing enzymes and drug transporters, and include the
      constitutive androstane receptor (CAR, NR1I3), the pregnane X receptor (PXR,
      NR1I2) and the aryl hydrocarbon receptor (AhR). This review will focus on the
      methods currently used to assess activation of these receptors. Assessment of
      nuclear receptor activation can be accomplished using direct or indirect
      approaches. Indirect methods quantify specific gene products that result from
      nuclear receptor activation while direct approaches measure either the binding of
      ligands to the receptors or the transcriptional events produced by ligand
      binding. Assays that directly quantify nuclear receptor activation are growing in
      popularity and, importantly, are amenable to high throughput screening (HTS).
      Several ligand binding assays are currently being utilized, including radioligand
      competition binding, where compounds compete with radiolabelled ligand for
      binding to PXR or CAR, such as the scintillation proximity binding assay that
      measures the reaction of ligands with receptor-coated beads. A fluorescence
      resonance energy transfer assay has also been developed, where the fluorescent
      signal is generated via the ligand-dependent interaction between the
      fluorescently-labeled ligand binding domain of a nuclear receptor and co
      activator proteins. Other in vitro activation assays include transient- and
      stably-transfected cell lines incorporating an expression vector for PXR, CAR or
      AhR plus a reporter gene vector containing response elements. The methods focused
      on in this review will be limited to the more direct in vitro approaches that are
      amenable to high throughput screening.

PMID- 21189135
TI  - Targeting intestinal transporters for optimizing oral drug absorption.
AB  - While the oral exposure continues to be the major focus, the chemical space of
      recent drug discovery is apparently trending towards more hydrophilic libraries,
      due to toxicity and drug-interactions issues usually reported with lipophilic
      drugs. This trend may bring in challenges in optimizing the membrane permeability
      and thus the oral absorption of new chemical entities. It is now apparent that
      the influx transporters such as peptide transporter 1 (PepT1), organic-anion
      transporting polypeptides (OATPs), monocarboxylate transporters (MCT1)
      facilitate, while efflux pumps (e.g. P-glycoprotein (P-gp), breast cancer
      resistance protein (BCRP)) limit oral absorption of drugs. This review will focus
      on intestinal transporters that may be targeted to achieve optimal clinical oral
      plasma exposure for hydrophilic and polar drugs. The structure, mechanism,
      structure-activity relationships and the clinical examples on the functional role
      of these transporters in the drug absorption was discussed. Physicochemical
      properties, lipophilicity and hydrogen-bonding ability, show good correlation
      with transport activity for efflux pumps. Although several attempts were made to
      describe the structural requirements based on pharmacophore modeling, lack of
      crystal structure of transporters impeded identification of definite properties
      for transporter affinity and favorable transport activity. Furthermore, very few
      substrate drug datasets are currently available for the influx transporters to
      derive any clear relationships. Unfortunately, gaps also exist in the translation
      of in vitro end points to the clinical relevance of the transporter(s) involved.
      However, it may be qualitatively generalized that targeting intestinal
      transporters are relevant for drugs with high solubility and/or low passive
      permeability i.e. a class of compounds identified as Class III and Class IV
      according to the Biopharmaceutic Classification System (BCS) and the
      Biopharmaceutic Drug Disposition Classification System (BDDCS). A careful
      considerations to oral dose based on the transporter clearance (V(max)/K(m))
      capacity is needed in targeting a particular transporter. For example, low
      affinity and high capacity uptake transporters such as PEPT1 and MCT1 may be
      targeted for high oral dose drugs.

PMID- 21189137
TI  - PBPK modeling of intestinal and liver enzymes and transporters in drug absorption
      and sequential metabolism.
AB  - Experimental strategies have long been applied for in vitro or in vivo evaluation
      of the effect of transporters and/or enzymes on the bioavailability. However, the
      lack of specific inhibitors or inducers of transporters and enzymes and the
      multiplicity of nuclear receptors in gene regulation and cross talk have led to
      compromised assessment of these effects in vivo. These and other causes have
      resulted in confusion and controversy in transporter-enzyme interplay. In this
      review, physiologically-based pharmacokinetic (PBPK) intestinal and liver models
      are utilized to predict the contributions of enzymes and transporters on
      intestinal availability (F(I)) and hepatic availability (F(H)), with the aim to
      fully understand the impact of these variables on bioavailability (F(sys)) in
      vivo. We emphasize the often overlooked impact of influx and efflux clearances,
      and apply the PBPK models and their solutions to examine individual organ
      clearances of the intestine and the liver. In order to accurately predict oral
      bioavailability, these organ models are incorporated into the whole body PBPK
      model, and additional complicated scenarios such as segmental differences and
      zonal heterogeneity of transporters and enzymes in the intestine and liver and
      segregated blood flow patterns of the intestine are further discussed. The
      sequential metabolism of a drug to form primary and secondary metabolites in the
      first-pass organs is considered in PBPK modeling, revealing that the segregated
      flow model (SFM) of the intestine is more appropriate than the traditional PBPK
      intestinal model (TM). Examples are included to highlight the potential
      application of these PBPK models on the quantitative prediction of
      bioavailability.

PMID- 21189138
TI  - The role of intestinal carboxylesterase in the oral absorption of prodrugs.
AB  - The bioavailability of therapeutic agents can be improved by using prodrugs which
      have better passive diffusion than the active agents. Intestinal hydrolysis is an
      important reaction in the bioconversion of prodrugs, and may be the rate-limiting
      factor in their absorption. Carboxylesterase (CES) is ubiquitous in most organs
      and is located in the endoplasmic reticulum. Single-pass perfusion experiments in
      rat intestine have shown that CES is the main enzyme involved in intestinal first
      pass hydrolysis. In man, intestinal CESs belong to the CES2 gene family and their
      activity is nearly constant along the jejunum and ileum. The predominant human
      intestinal CES, hCE2, preferentially hydrolyzes prodrugs in which the alcohol
      group of a pharmacologically active molecule has been modified by the addition of
      a small acyl group. In preclinical animal models, CES2 isozymes are also the
      major intestinal enzymes although they have different substrate specificities to
      human CES2, while CES1 isozymes and other unidentified enzymes are also present.
      It is therefore difficult to predict human intestinal absorption from animal
      experiments. Caco-2 cells mainly express the human CES1 isozyme, hCE1, which
      shows quite different substrate specificity from hCE2, making Caco-2 cells
      unsuitable for prediction of human intestinal absorption of prodrugs. However, we
      have developed a novel experimental method for predicting the human intestinal
      absorption of prodrugs using Caco-2 cells in which CES-mediated hydrolysis has
      been inhibited. The expression of hCE2 shows inter-individual variation and is
      regulated by several mechanisms, such as gene polymorphism and epigenetic
      processes. There are no reports suggesting that severe toxicity is associated
      with prodrugs due to genetic polymorphism of the CES2 gene.

PMID- 21189139
TI  - Predicting drug-drug interactions involving the inhibition of intestinal CYP3A4
      and P-glycoprotein.
AB  - Recently, interest has grown in drug-drug interactions (DDIs) involving the
      inhibition of intestinal CYP3A4, P-glycoprotein (P-gp), and other drug efflux
      transporters. The criteria for intestinal DDIs are described in the draft
      guidances of the US Food and Drug Administration (FDA) and European Medicines
      Agency (EMA). Substrate drugs with small fraction absorbed (Fa) and/or low
      intestinal availability (Fg) as a result of intestinal efflux transport and
      metabolism are important as "victim" drugs because these substrates are likely to
      show considerable interactions. The susceptibility of a victim drug to intestinal
      interactions can be evaluated from its FaFg. In this review, methods for
      estimating the FaFg of substrate drugs are discussed. The nonlinear
      pharmacokinetics of substrate drugs caused by the saturation of intestinal
      CYP3A4/P-gp is also discussed. The methods for predicting intestinal DDIs caused
      by inhibitor drugs are then summarized. Because the prediction accuracy of
      intestinal DDIs also depends on the inhibition constant (Ki) estimated in in
      vitro studies, these in vitro methods of estimating Ki are also discussed.
      Standardized methods for predicting intestinal DDIs have not yet been
      established. Further studies are required to establish more accurate and
      standardized prediction methods.

PMID- 21189136
TI  - Influence of dietary substances on intestinal drug metabolism and transport.
AB  - Successful delivery of promising new chemical entities via the oral route is rife
      with challenges, some of which cannot be explained or foreseen during drug
      development. Further complicating an already multifaceted problem is the obvious,
      yet often overlooked, effect of dietary substances on drug disposition and
      response. Some dietary substances, particularly fruit juices, have been shown to
      inhibit biochemical processes in the intestine, leading to altered
      pharmacokinetic (PK), and potentially pharmacodynamic (PD), outcomes. Inhibition
      of intestinal CYP3Amediated metabolism is the major mechanism by which fruit
      juices, including grapefruit juice, enhances systemic exposure to new and already
      marketed drugs. Inhibition of intestinal non-CYP3A enzymes and apically-located
      transport proteins represent recently identified mechanisms that can alter PK and
      PD. Several fruit juices have been shown to inhibit these processes in vitro, but
      some interactions have not translated to the clinic. The lack of in vitroin vivo
      concordance is due largely to a lack of rigorous methods to elucidate causative
      ingredients prior to clinical testing. Identification of specific components and
      underlying mechanisms is challenging, as dietary substances frequently contain
      multiple, often unknown, bioactive ingredients that vary in composition and
      bioactivity. A translational research approach, combining expertise from clinical
      pharmacologists and natural products chemists, is needed to develop robust models
      describing PK/PD relationships between a given dietary substance and drug of
      interest. Validation of these models through well-designed clinical trials would
      facilitate development of common practice guidelines for managing drug-dietary
      substance interactions appropriately.

PMID- 21189140
TI  - Interplay of metabolism and transport in determining oral drug absorption and gut
      wall metabolism: a simulation assessment using the "Advanced Dissolution,
      Absorption, Metabolism (ADAM)" model.
AB  - Bioavailability of orally administered drugs can be influenced by a number of
      factors including release from the formulation, dissolution, stability in the
      gastrointestinal (GI) environment, permeability through the gut wall and first
      pass gut wall and hepatic metabolism. Although there are various enzymes in the
      gut wall which may contribute to gut first pass metabolism, Cytochrome P450 (CYP)
      3A has been shown to play a major role. The efflux transporter P-glycoprotein (P
      gp; MDR1/ABCB1) is the most extensively studied drug efflux transporter in the
      gut and might have a significant role in the regulation of GI absorption.
      Although not every CYP3A substrate will have a high extent of gut wall first-pass
      extraction, being a substrate for the enzyme increases the likelihood of a higher
      first-pass extraction. Similarly, being a P-gp substrate does not necessarily
      pose a problem with the gut wall absorption however it may reduce bioavailability
      in some cases (e.g. when drug has low passive permeability). An on-going debate
      has focused on the issue of the interplay between CYP3A and P-gp such that high
      affinity to P-gp increases the exposure of drug to CYP3A through repeated cycling
      via passive diffusion and active efflux, decreasing the fraction of drug that
      escapes first pass gut metabolism (F(G)). The presence of P-gp in the gut wall
      and the high affinity of some CYP3A substrates to this transporter are postulated
      to reduce the potential for saturating the enzymes, thus increasing gut wall
      first-pass metabolism for compounds which otherwise would have saturated CYP3A.
      Such inferences are based on assumptions in the modelling of oral drug
      absorption. These models should be as mechanistic as possible and tractable using
      available in vitro and in vivo information. We review, through simulation, this
      subject and examine the interplay between gut wall metabolism and efflux
      transporters by studying the fraction of dose absorbed into enterocytes (F(a))
      and F(G) via systematic variation of drug characteristics, in accordance with the
      Biopharmaceutics Classification System (BCS) within one of the most physiological
      models of oral drug absorption currently available, respectively ADAM. Variables
      studied included the intrinsic clearance (CLint) and the Michaelis-Menten
      Constant (Km) for CYP3A4 and P-gp (C(Lint-CYP3A4) and K(m-CYP3A4), CL(int-P-gp)
      and K(m-P-gp)). The impact of CYP3A4 and P-gp intracellular topography were not
      investigated since a well-stirred enterocyte is assumed within ADAM. An increased
      CLint-CYP3A4 resulted in a reduced F(G) whereas an increase in C(Lint-P-gp)
      resulted in a reduced F(a), but interestingly decreased F(G) too. The reduction
      in FG was limited to certain conditions and was modest. Non-linear relationships
      between various parameters determining the permeability (e.g. P(app), C(Lint-P
      gp,) and K(m-P-gp)) and gut wall metabolism (e.g. C(Lint-CYP3A4,) K(m-CYP3A4))
      resulted in disproportionate changes in F(G) compared to the magnitude of
      singular effects. The results suggest that P-gp efflux decreases enterocytic drug
      concentration for drugs given at reasonably high dose which possess adequate
      passive permeability (high P(app)), by de-saturating CYP3A4 in the gut resulting
      in a lower F(G). However, these findings were observed only in a very limited
      area of the parameters space matching very few therapeutic drugs (a group with
      very high metabolism, high turn-over by efflux transporters and low F(a)). The
      systematic approach in this study enabled us to recognise the combination of
      parameters values where the potential interplay between metabolising enzymes and
      efflux transporters is expected to be highest, using a realistic range of
      parameter values taken from an intensive literature search.

PMID- 21189142
TI  - Deqi sensations without cutaneous sensory input: results of an RCT.
AB  - BACKGROUND: Deqi is defined in relation to acupuncture needling as a sensory
      perception of varying character. In a recently published sham laser validation
      study, we found that subjects in the verum and the sham laser group experienced
      deqi sensations. Therefore, we aim to further analyze whether the perceptions
      reported in the two study arms were distinguishable and whether expectancy
      effects exhibited considerable impact on our results. METHODS: A detailed re
      analysis focusing on deqi sensations was performed from data collected in a
      previously published placebo-controlled, double-blind, clinical cross-over trial
      for a sham laser evaluation. Thirty-four healthy volunteers (28 +/- 10.7 years;
      16 women, 18 men) received two laser acupuncture treatments at three acupuncture
      points LI4 (hegu), LU7 (lieque), and LR3 (taichong); once by verum laser and once
      using a sham device containing an inactive laser in randomized order. Outcome
      measures were frequency, intensity (evaluated by visual analogue scale; VAS), and
      quality of the subjects' sensations perceived during treatments (assessed with
      the "acupuncture sensation scale"). RESULTS: Both, verum and the sham laser
      acupuncture result in similar deqi sensations with regard to frequency (p-value =
      0.67), intensity (p-value = 0.71) and quality (p-values between 0.15 - 0.98). In
      both groups the most frequently used adjectives to describe these perceptions
      were "spreading", "radiating", "tingling", "tugging", "pulsing", "warm", "dull",
      and "electric". Sensations reported were consistent with the perception of deqi
      as previously defined in literature. Subjects' conviction regarding the
      effectiveness of laser acupuncture or the history of having received acupuncture
      treatments before did not correlate with the frequency or intensity of sensations
      reported. CONCLUSIONS: Since deqi sensations, described as sensory perceptions,
      were elicited without any cutaneous sensory input, we assume that they are a
      product of non-specific effects from the overall treatment procedure. Expectancy
      effects due to previous acupuncture experience and belief in laser acupuncture do
      not seem to play a major role in elicitation of deqi sensations. Our results give
      hints that deqi might be a central phenomenon of awareness and consciousness, and
      that its relevance should be taken into account, even in clinical trials.
      However, further research is required to understand mechanisms underlying deqi.

PMID- 21189143
TI  - Co-expression and impact of prostate specific membrane antigen and prostate
      specific antigen in prostatic pathologies.
AB  - BACKGROUND: The present study was undertaken to relate the co-expression of
      prostate-associated antigens, PSMA and PSA, with the degree of vascularization in
      normal and pathologic (hyperplasia and cancer) prostate tissues to elucidate
      their possible role in tumor progression. METHODS: The study was carried out in 6
      normal, 44 benign prostatic hyperplastic and 39 cancerous human prostates.
      Immunohistochemical analysis were performed using the monoclonal antibody CD34 to
      determine the angiogenic activity, and the monoclonal antibodies 3E6 and ER-PR8
      to assess PSMA and PSA expression, respectively. RESULTS: In our study we found
      that in normal prostate tissue, PSMA and PSA were equally expressed (3.7 +/- 0.18
      and 3.07 +/- 0.11). A significant difference in their expression was see in
      hyperplastic and neoplastic prostates tissues (16.14 +/- 0.17 and 30.72 +/- 0.85,
      respectively) for PSMA and (34.39 +/- 0.53 and 17.85 +/- 1.21, respectively) for
      PSA. Study of prostate tumor profiles showed that the profile (PSA+, PSMA-)
      expression levels decreased between normal prostate, benign prostatic tissue and
      primary prostate cancer. In the other hand, the profile (PSA-, PSMA+) expression
      levels increased from normal to prostate tumor tissues. PSMA overexpression was
      associated with high intratumoral angiogenesis activity. By contrast, high PSA
      expression was associated with low angiogenesis activity. CONCLUSION: These data
      suggest that these markers are regulated differentially and the difference in
      their expression showed a correlation with malignant transformation. With regard
      to the duality PSMA-PSA, this implies the significance of their investigation
      together in normal and pathologic prostate tissues.

PMID- 21189141
TI  - Impact of sex hormone metabolism on the vascular effects of menopausal hormone
      therapy in cardiovascular disease.
AB  - Epidemiological studies have shown that cardiovascular disease (CVD) is less
      common in pre-menopausal women (Pre-MW) compared to men of the same age or post
      menopausal women (Post-MW), suggesting cardiovascular benefits of estrogen.
      Estrogen receptors (ERs) have been identified in the vasculature, and
      experimental studies have demonstrated vasodilator effects of estrogen/ER on the
      endothelium, vascular smooth muscle (VSM) and extracellular matrix. Several
      natural and synthetic estrogenic preparations have been developed for relief of
      menopausal vasomotor symptoms. However, whether menopausal hormone therapy (MHT)
      is beneficial in postmenopausal CVD remains controversial. Despite reports of
      vascular benefits of MHT from observational and experimental studies, randomized
      clinical trials (RCTs), such as the Heart and Estrogen/progestin Replacement
      Study (HERS) and the Women's Health Initiative (WHI), have suggested that,
      contrary to expectations, MHT may increase the risk of CVD. These discrepancies
      could be due to agerelated changes in sex hormone synthesis and metabolism, which
      would influence the effective dose of MHT and the sex hormone environment in Post
      MW. Age-related changes in the vascular ER subtype, structure, expression,
      distribution, and post-ER signaling pathways in the endothelium and VSM, along
      with factors related to the design of RCTs, preexisting CVD condition, and
      structural changes in the blood vessels architecture have also been suggested as
      possible causes of MHT failure in CVD. Careful examination of these factors
      should help in identifying the causes of the changes in the vascular effects of
      estrogen with age. The sex hormone metabolic pathways, the active versus inactive
      estrogen metabolites, and their effects on vascular function, the mitochondria,
      the inflammatory process and angiogenesis should be further examined. Also, the
      genomic and non-genomic effects of estrogenic compounds should be viewed as
      integrated rather than discrete responses. The complex interactions between these
      factors highlight the importance of careful design of MHT RCTs, and the need of a
      more customized approach for each individual patient in order to enhance the
      vascular benefits of MHT in postmenopausal CVD.

PMID- 21189144
TI  - Glyceraldehyde-3-phosphate dehydrogenase is largely unresponsive to low
      regulatory levels of hydrogen peroxide in Saccharomyces cerevisiae.
AB  - BACKGROUND: The reversible oxidation of protein SH groups has been considered to
      be the basis of redox regulation by which changes in hydrogen peroxide (H2O2)
      concentrations may control protein function. Several proteins become S
      glutathionylated following exposure to H2O2 in a variety of cellular systems. In
      yeast, when using a high initial H2O2 dose, glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) was identified as the major target of S-glutathionylation
      which leads to reversible inactivation of the enzyme. GAPDH inactivation by H2O2
      functions to reroute carbohydrate flux to produce NADPH. Here we report the
      effect of low regulatory H2O2 doses on GAPDH activity and expression in
      Saccharomyces cerevisiae. RESULTS: A calibrated and controlled method of H2O2
      delivery - the steady-state titration - in which cells are exposed to constant,
      low, and known H2O2 concentrations, was used in this study. This technique,
      contrary to the common bolus addition, allows determining which H2O2
      concentrations trigger specific biological responses. This work shows that both
      in exponential- and stationary-phase cells, low regulatory H2O2 concentrations
      induce a large upregulation of catalase, a fingerprint of the cellular oxidative
      stress response, but GAPDH oxidation and the ensuing activity decrease are only
      observed at death-inducing high H2O2 doses. GAPDH activity is constant upon
      incubation with sub-lethal H2O2 doses, but in stationary-phase cells there is a
      differential response in the expression of the three GAPDH isoenzymes: Tdh1p is
      strongly upregulated while Tdh2p/Tdh3p are slightly downregulated. CONCLUSIONS:
      In yeast GAPDH activity is largely unresponsive to low to moderate H2O2 doses.
      This points to a scenario where (a) cellular redoxins efficiently cope with
      levels of GAPDH oxidation induced by a vast range of sub-lethal H2O2
      concentrations, (b) inactivation of GAPDH cannot be considered a sensitive
      biomarker of H2O2-induced oxidation in vivo. Since GAPDH inactivation only occurs
      at cell death-inducing high H2O2 doses, GAPDH-dependent rerouting of carbohydrate
      flux is probably important merely in pathophysiological situations. This work
      highlights the importance of studying H2O2-induced oxidative stress using
      concentrations closer to the physiological for determining the importance of
      protein oxidation phenomena in the regulation of cellular metabolism.

PMID- 21189145
TI  - Exploring the use of internal and externalcontrols for assessing microarray
      technical performance.
AB  - BACKGROUND: The maturing of gene expression microarray technology and interest in
      the use of microarray-based applications for clinical and diagnostic applications
      calls for quantitative measures of quality. This manuscript presents a
      retrospective study characterizing several approaches to assess technical
      performance of microarray data measured on the Affymetrix GeneChip platform,
      including whole-array metrics and information from a standard mixture of external
      spike-in and endogenous internal controls. Spike-in controls were found to carry
      the same information about technical performance as whole-array metrics and
      endogenous "housekeeping" genes. These results support the use of spike-in
      controls as general tools for performance assessment across time, experimenters
      and array batches, suggesting that they have potential for comparison of
      microarray data generated across species using different technologies. RESULTS: A
      layered PCA modeling methodology that uses data from a number of classes of
      controls (spike-in hybridization, spike-in polyA+, internal RNA degradation,
      endogenous or "housekeeping genes") was used for the assessment of microarray
      data quality. The controls provide information on multiple stages of the
      experimental protocol (e.g., hybridization, RNA amplification). External spike
      in, hybridization and RNA labeling controls provide information related to both
      assay and hybridization performance whereas internal endogenous controls provide
      quality information on the biological sample. We find that the variance of the
      data generated from the external and internal controls carries critical
      information about technical performance; the PCA dissection of this variance is
      consistent with whole-array quality assessment based on a number of quality
      assurance/quality control (QA/QC) metrics. CONCLUSIONS: These results provide
      support for the use of both external and internal RNA control data to assess the
      technical quality of microarray experiments. The observed consistency amongst the
      information carried by internal and external controls and whole-array quality
      measures offers promise for rationally-designed control standards for routine
      performance monitoring of multiplexed measurement platforms.

PMID- 21189146
TI  - Racial disparities in infant mortality: what has birth weight got to do with it
      and how large is it?
AB  - BACKGROUND: It has been hypothesized that birth weight is not on the causal
      pathway to infant mortality, at least among "normal" births (i.e. those located
      in the central part of the birth weight distribution), and that US racial
      disparities (African American versus European American) may be underestimated.
      Here these hypotheses are tested by examining the role of birth weight on racial
      disparities in infant mortality. METHODS: A two-component Covariate Density
      Defined mixture of logistic regressions model is used to decompose racial
      disparities, 1) into disparities due to "normal" versus "compromised" components
      of the birth cohort, and 2) further decompose these components into indirect
      effects, which are associated with birth weight, versus direct effects, which are
      independent of birth weight. RESULTS: The results indicate that a direct effect
      is responsible for the racial disparity in mortality among "normal" births. No
      indirect effect of birth weight is observed despite significant disparities in
      birth weight. Among "compromised" births, an indirect effect is responsible for
      the disparity, which is consistent with disparities in birth weight. However,
      there is also a direct effect among "compromised" births that reduces the racial
      disparity in mortality. This direct effect is responsible for the "pediatric
      paradox" and maybe due to differential fetal loss. Model-based adjustment for
      this effect indicates that racial disparities corrected for fetal loss could be
      as high as 3 or 4 fold. This estimate is higher than the observed racial
      disparities in infant mortality (2.1 for both sexes). CONCLUSIONS: The results
      support the hypothesis that birth weight is not on the causal pathway to infant
      mortality among "normal" births, although birth weight could play a role among
      "compromised" births. The overall size of the US racial disparities in infant
      mortality maybe considerably underestimated in the observed data possibly due to
      racial disparities in fetal loss.

PMID- 21189147
TI  - Unusual conservation of mitochondrial gene order in Crassostrea oysters: evidence
      for recent speciation in Asia.
AB  - BACKGROUND: Oysters are morphologically plastic and hence difficult subjects for
      taxonomic and evolutionary studies. It is long been suspected, based on the
      extraordinary species diversity observed, that Asia Pacific is the epicenter of
      oyster speciation. To understand the species diversity and its evolutionary
      history, we collected five Crassostrea species from Asia and sequenced their
      complete mitochondrial (mt) genomes in addition to two newly released Asian
      oysters (C. iredalei and Saccostrea mordax) for a comprehensive analysis.
      RESULTS: The six Asian Crassostrea mt genomes ranged from 18,226 to 22,446 bp in
      size, and all coded for 39 genes (12 proteins, 2 rRNAs and 25 tRNAs) on the same
      strand. Their genomes contained a split of the rrnL gene and duplication of trnM,
      trnK and trnQ genes. They shared the same gene order that differed from an
      Atlantic sister species by as many as nine tRNA changes (6 transpositions and 3
      duplications) and even differed significantly from S. mordax in protein-coding
      genes. Phylogenetic analysis indicates that the six Asian Crassostrea species
      emerged between 3 and 43 Myr ago, while the Atlantic species evolved 83 Myr ago.
      CONCLUSIONS: The complete conservation of gene order in the six Asian Crassostrea
      species over 43 Myr is highly unusual given the remarkable rate of rearrangements
      in their sister species and other bivalves. It provides strong evidence for the
      recent speciation of the six Crassostrea species in Asia. It further indicates
      that changes in mt gene order may not be strictly a function of time but subject
      to other constraints that are presently not well understood.

PMID- 21189148
TI  - Guidelenines in the management of obstructing cancer of the left colon: consensus
      conference of the world society of emergency surgery (WSES) and peritoneum and
      surgery (PnS) society.
AB  - BACKGROUND: Obstructive left colon carcinoma (OLCC) is a challenging matter in
      terms of obstruction release as well of oncological issues. Several options are
      available and no guidelines are established. The paper aims to generate evidenced
      based recommendations on management of OLCC. METHODS: The PubMed and Cochrane
      Library databases were queried for publications focusing on OLCC published prior
      to April 2010. A extensive retrieval, analyses, and grading of the literature was
      undertaken. The findings of the research were presented and largely discussed
      among panellist and audience at the Consensus Conference of the World Society of
      Emergency Surgery (WSES) and Peritoneum and Surgery (PnS) Society held in Bologna
      July 2010. Comparisons of techniques are presented and final committee
      recommendation are enounced. RESULTS: Hartmann's procedure should be preferred to
      loop colostomy (Grade 2B). Hartmann's procedure offers no survival benefit
      compared to segmental colonic resection with primary anastomosis (Grade 2C+);
      Hartmann's procedure should be considered in patients with high surgical risk
      (Grade 2C). Total colectomy and segmental colectomy with intraoperative colonic
      irrigation are associated with same mortality/morbidity, however total colectomy
      is associated with higher rates impaired bowel function (Grade 1A). Segmental
      resection and primary anastomosis either with manual decompression or
      intraoperative colonic irrigation are associated with same mortality/morbidity
      rate (Grade 1A). In palliation stent placement is associated with similar
      mortality/morbidity rates and shorter hospital stay (Grade 2B). Stents as a
      bridge to surgery seems associated with lower mortality rate, shorter hospital
      stay, and a lower colostomy formation rate (Grade 1B). CONCLUSIONS: Loop
      colostomy and staged procedure should be adopted in case of dramatic scenario,
      when neoadjuvant therapy could be expected. Hartmann's procedure should be
      performed in case of high risk of anastomotic dehiscence. Subtotal and total
      colectomy should be attempted when cecal perforation or in case of synchronous
      colonic neoplasm. Primary resection and anastomosis with manual decompression
      seems the procedure of choice. Colonic stents represent the best option when
      skills are available. The literature power is relatively poor and the existing
      RCT are often not sufficiently robust in design thus, among 6 possible treatment
      modalities, only 2 reached the Grade A.

PMID- 21189150
TI  - Meta-analysis of quantitative diffusion-weighted MR imaging in the differential
      diagnosis of breast lesions.
AB  - BACKGROUND: To determine, in a meta-analysis, the diagnostic performance of
      quantitative diffusion-weighted (DW) MR imaging in patients with breast lesions.
      METHODS: English and Chinese studies published prior to June 2009 to assess the
      diagnostic performance of quantitative DWI in patients with breast lesions were
      reviewed and summarized with reference to the inclusion and exclusion criteria.
      Methodological quality was assessed by using the quality assessment of diagnostic
      studies (QUADAS) instrument. Publication bias analysis was performed by using
      Comprehensive Meta-analysis version 2. Meta-Disc version 1.4 was used to describe
      primary results and explore homogeneity by Chi-square test and inconsistency
      index; to explore threshold effect by receiver operator characteristic (ROC)
      space and Spearman correlation coefficient; and to pool weighted sensitivity and
      specificity by fixed or random effect model. A summary ROC (sROC) curve was
      constructed to calculate the area under the curve (AUC). RESULTS: Of 65 eligible
      studies, 13 with 615 malignant and 349 benign lesions were included in the
      original meta-analysis, among which heterogeneity arising from factors other than
      threshold effect and publication bias was explored. Methodological quality was
      moderate. The pooled weighted sensitivity and specificity with corresponding 95%
      confidence interval (CI) in one homogenous subgroup of studies using maximum b =
      1000 s/mm2 were 0.84 (0.80, 0.87) and 0.84 (0.79, 0.88) respectively. AUC of sROC
      was 0.9085. Sensitivity analysis demonstrated that the pooled estimates were
      stable and reliable. CONCLUSIONS: Quantitative DWI has a higher specificity to
      differentiate between benign and malignant breast lesions compared to that of
      contrast-enhanced MRI. However, large scale randomized control trials (RCTs) are
      necessary to assess its clinical value because of disunified diffusion gradient
      factor b and diagnosis threshold.

PMID- 21189149
TI  - Digit ratios by computer-assisted analysis confirm lack of anatomical evidence of
      prenatal androgen exposure in clinical phenotypes of polycystic ovary syndrome.
AB  - BACKGROUND: We recently showed that women with four clinical phenotypes of
      polycystic ovary syndrome (PCOS) do not demonstrate anatomical evidence of
      elevated prenatal androgen exposure as judged by a lower ratio of the index (2D)
      to ring (4D) finger. However, those findings conflicted with a previous study
      where women with PCOS had lower right hand 2D:4D compared to healthy female
      controls. Both these studies used Vernier calipers to measure finger lengths--a
      method recently shown to be less reliable at obtaining finger length measurements
      than computer-assisted analysis. METHODS: Ninety-six women diagnosed with PCOS
      according to the 2003 Rotterdam criteria had their finger lengths measured with
      computer-assisted analysis. Participants were categorized into four recognized
      phenotypes of PCOS and their 2D:4D compared to healthy female controls (n = 48)
      and men (n = 50). RESULTS: Digit ratios assessed by computer-assisted analysis in
      women with PCOS did not differ from female controls, but were significantly lower
      in men. When subjects were stratified by PCOS phenotype, 2D:4D did not differ
      among phenotypes or when compared to female controls. CONCLUSION: Computer
      assisted measurements validated that digit ratios of women with PCOS do not show
      anatomical evidence of increased prenatal androgen exposure.

PMID- 21189151
TI  - Long-term treatment with fluticasone propionate/salmeterol via Diskus improves
      asthma control versus fluticasone propionate alone.
AB  - This 52-week study was designed to assess the safety and efficacy of fluticasone
      propionate/salmeterol combination (FSC) 250/50 micrograms versus fluticasone
      propionate (FP) 250 micrograms in subjects with persistent asthma symptomatic on
      open-label FP 100 micrograms. The primary objective of this study was to show
      that FSC 250/50 micrograms was superior to FP 250 micrograms at increasing
      pulmonary function as measured by forced expiratory volume in 1 second over a 52
      week treatment period. A secondary objective was to compare the rate of asthma
      attacks defined as (1) a sustained 2-day decrease in morning peak expiratory flow
      or increase in albuterol use for 2 consecutive days, (2) an asthma exacerbation
      requiring systemic corticosteroids, or (3) an unscheduled clinic or hospital
      visit for acute asthma symptoms. Three hundred six subjects received FSC 250/50
      micrograms and 315 subjects received FP 250 micrograms. Both treatments were
      administered twice daily. Treatment with FSC 250/50 micrograms resulted in a
      significant improvement in lung function compared with FP 250 micrograms (p <
      0.001). Additionally, treatment with FSC 250/50 micrograms resulted in a
      reduction in the rate of exacerbations of asthma (i.e., requiring systemic
      corticosteroids or unscheduled urgent care intervention) compared with FP 250
      micrograms (0.170 versus 0.273, respectively; p = 0.017). There was no
      differentiation between treatments for less severe attacks of asthma. FSC 250/50
      micrograms showed consistently greater improvement in lung function, symptom
      control, and decreased albuterol use. In addition, FSC 250/50 micrograms-treated
      subjects experienced fewer severe asthma exacerbations than subjects treated with
      FP 250 micrograms.

PMID- 21189152
TI  - A non-replicating oncolytic vector as a novel therapeutic tool against cancer.
AB  - Cancers are still difficult targets despite recent advances in cancer therapy.
      Due to the heterogeneity of cancer, a single-treatment modality is insufficient
      for the complete elimination of cancer cells. Therapeutic strategies from various
      aspects are needed. Gene therapy has been expected to bring a breakthrough to
      cancer therapy, but it has not yet been successful. Gene therapy also should be
      combined with other treatments to enhance multiple therapeutic pathways. In this
      view, gene delivery vector itself should be equipped with intrinsic anti-cancer
      activities. HVJ (hemagglutinating virus of Japan; Sendai virus) envelope vector
      (HVJ-E) was developed to deliver therapeutic molecules. HVJ-E itself possessed
      anti-tumor activities such as the generation of anti-tumor immunities and the
      induction of cancer-selective apoptosis. In addition to the intrinsic anti-tumor
      activities, therapeutic molecules incorporated into HVJ-E enabled to achieve
      multi-modal therapeutic strategies in cancer treatment. Tumor-targeting HVJ-E was
      also developed. Thus, HVJ-E will be a novel promising tool for cancer treatment.

PMID- 21189153
TI  - Current advances in adenovirus nanocomplexes: more specificity and less
      immunogenicity.
AB  - An often overlooked issue in the field of adenovirus (Ad)-mediated cancer gene
      therapy is its limited capacity for effective systemic delivery. Although primary
      tumors can be treated effectively with intralesional injection of conventional Ad
      vectors, systemic metastasis is difficult to cure. Systemic administration of
      conventional naked Ads leads to acute accumulation of Ad particles in the liver,
      induction of neutralizing antibody, short blood circulation half-life, non
      specific biodistribution in undesired organs, and low selective accumulation in
      the target disease site. Versatile strategies involving the modification of viral
      surfaces with polymers and nanomaterials have been designed for the purpose of
      maximizing Ad anti-tumor activity and specificity by systemic administration.
      Integration of viral and non-viral nanomaterials will substantially advance both
      fields, creating new concepts in gene therapeutics. This review focuses on
      current advances in the development of smart Ad hybrid nanocomplexes based on
      various design-based strategies for optimal Ad systemic administration.

PMID- 21189154
TI  - Cloning and characterization of a novel gene with alternative splicing in murine
      mesenchymal stem cell line C3H/10T1/2 by gene trap screening.
AB  - A novel gene, designated mgt-6, containing four splicing variants, was isolated
      from a gene trap clone library of C3H/10T1/2 cells transfected with retroviral
      promoterless gene-trap vector, ROSAFARY. The transcript variants were
      differentially expressed in murine tissues and cell lines and differentially
      responded to diverse stimuli including TGF-beta1 and mitogen-activated protein
      kinase (MAPK) inhibitors. The mgt-6 gene encoded a protein of 37 or 11 amino acid
      residuals with cytoplasmic distribution. However, when C3H/10T1/2 cells were
      treated with 5-azacytidine, the protein translocated into cell nucleus as
      indicated by fused LacZ or C-terminally tagged EGFP. Our preliminary results
      suggest that further study on the role of mgt-6 gene in cell transformation and
      differentiation may be of significance.

PMID- 21189155
TI  - Huntingtin-interacting protein 1-related is required for accurate congression and
      segregation of chromosomes.
AB  - Huntingtin-interacting protein 1-related (HIP1r) is known to function in clathrin
      mediated endocytosis and regulation of the actin cytoskeleton, which occurs
      continuously in non-dividing cells. This study reports a new function for HIP1r
      in mitosis. Green fluorescent protein-fused HIP1r localizes to the mitotic
      spindles. Depletion of HIP1r by RNA interference induces misalignment of
      chromosomes and prolonged mitosis, which is associated with decreased
      proliferation of HIP1r-deficeint cells. Chromosome misalignment leads to
      missegregation and ultimately production of multinucleated cells. Depletion of
      HIP1r causes persistent activation of the spindle checkpoint in misaligned
      chromosomes. These findings suggest that HIP1r plays an important role in
      regulating the attachment of spindle microtubules to chromosomes during mitosis,
      an event that is required for accurate congression and segregation of
      chromosomes. This finding may provide new insights that improve the understanding
      of various human diseases involving HIP1r as well as its fusion genes.

PMID- 21189156
TI  - Soluble expression, purification and the role of C-terminal glycine residues in
      scorpion toxin BmK AGP-SYPU2.
AB  - The existence of glycine residues in long-chain scorpion toxins has been well
      documented. However, their role as analgesics has not been evaluated. To address
      this issue, we investigated the functional role of glycines in the C-terminal end
      of Chinese-scorpion toxin from Buthus martensii Karsch (BmK AGP-SYPU2) using site
      directed mutagenesis and analgesic activity assays. Recombinant BmK AGP-SYPU2 and
      its mutants were efficiently expressed in E. coli and purified to homogeneity
      using immobilized metal ion affinity chromatography (IMAC) and cation exchange
      chromatography. The mouse-twisting test was used to detect the analgesic activity
      of BmK AGP-SYPU2 and its mutants. As a result, we identified glycines at the C
      terminal end that, when altered, significantly affected analgesic activity. Also,
      Mut6566 was significantly decreased compared to BmK AGP-SYPU2. These data
      indicate that the glycines at the C-terminal end are important for the analgesic
      activity of BmK AGP-SYPU2.

PMID- 21189157
TI  - ZAS3 represses NFkappaB-dependent transcription by direct competition for DNA
      binding.
AB  - NFkappaB and ZAS3 are transcription factors that control important cellular
      processes including immunity, cell survival and apoptosis. Although both proteins
      bind the kappaB-motif, they produce opposite physiological consequences; NFkappaB
      activates transcription, promotes cell growth and is often found to be
      constitutively expressed in cancer cells, while ZAS3 generally represses
      transcription, inhibits cell proliferation and is downregulated in some cancers.
      Here, we show that ZAS3 inhibits NFkappaB-dependent transcription by competing
      with NFkappaB for the kappaB-motif. Transient transfection studies show that N
      terminal 645 amino acids is sufficient to repress transcription activated by
      NFkappaB, and that the identical region also possesses intrinsic repression
      activity to inhibit basal transcription from a promoter. Finally, in vitro DNA
      protein interaction analysis shows that ZAS3 is able to displace NFkappaB by
      competing with NFkappaB for the kappaB-motif. It is conceivable that ZAS3 has
      therapeutic potential for controlling aberrant activation of NFkappaB in various
      diseases.

PMID- 21189158
TI  - Fluridone affects quiescent centre division in the Arabidopsis thaliana root stem
      cell niche.
AB  - Plants undergo cell division throughout their life in order to maintain their
      growth. It is well known that root and shoot tip of plants possess meristems,
      which contain quiescent cells. Fluridone (1-methyl-3-phenyl-5-(3-trifluoromethyl
      (phenyl))-4-(1H)-pyridinone) is an established inhibitor of both ABA and
      carotenoid biosynthesis. However, the other functions of fluridone remain
      undiscovered. In this report, we provide experimental evidence that fluridone
      plays a role in the division of the quiescent centre of the Arabidopsis root
      meristem. This study examined the effects of exogenous fluridone and ABA on the
      development of the stem cell niche in Arabidopsis root. We show that fluridone
      promoted the division of stem cells in the quiescent centre, whereas exogenous
      ABA suppressed quiescent centre division. Furthermore, we established a novel
      regulatory function for fluridone by demonstrating that it plays an important
      role in postembryonic development.

PMID- 21189159
TI  - Rapid functional screening of effective siRNAs against Plk1 and its growth
      inhibitory effects in laryngeal carcinoma cells.
AB  - Plk 1 is overexpressed in many human malignancies including laryngeal carcinoma.
      However, its therapeutic potential has been never examined in laryngeal
      carcinoma. In the present study, a simple cellular morphology-based strategy was
      firstly proposed for rapidly screening the effective siRNAs against Plk1.
      Furthermore, we investigated the effects of Plk1 depletion via a novel identified
      effective siRNA against Plk1, Plk1 siRNA-607, on human laryngeal carcinoma Hep-2
      cells. The results indicated that Plk1 siRNA-607 transfection resulted in a
      significant inhibition in Plk1 expression in cells, and subsequently caused a
      dramatic mitotic cell cycle arrest followed by massive apoptotic cell death, and
      eventually resulted in a significant decrease in growth and viability of the
      laryngeal carcinoma cells. Taken together, our present study not only suggests a
      simple strategy for rapidly screening effective siRNAs against Plk1 but also
      implicates that Plk1 may serve as a potential therapeutic target in human
      laryngeal carcinoma.

PMID- 21189160
TI  - Beta-carboline alkaloids harmaline and harmalol induce melanogenesis through p38
      mitogen-activated protein kinase in B16F10 mouse melanoma cells.
AB  - Melanin synthesis is regulated by melanocyte specific enzymes and related
      transcription factors. beta-carboline alkaloids including harmaline and harmalol
      are widely distributed in the environment including several plant families and
      alcoholic beverages. Presently, melanin content and tyrosinase activity were
      increased in melanoma cells by harmaline and harmalol in concentration- and time
      dependent manners. Increased protein levels of tyrosinase, tyrosinase-related
      protein-1 (TRP-1), and TRP-2 were also evident. In addition, immunofluorescence
      and Western blot analyses revealed harmaline and harmalol increased cAMP response
      element binding protein phosphorylation and microphthalmia-associated
      transcription factor expression. In addition to studying the signaling that leads
      to melanogenesis, roles of the p38 MAPK pathways by the harmaline and harmalol
      were investigated. Harmaline and harmalol induced time-dependent phosphorylation
      of p38 MAPK. Harmaline and harmalol stimulated melanin synthesis and tyrosinase
      activity, as well as expression of tyrosinase and TRP-1 and TRP-2 indicating that
      these harmaline and harmalol induce melanogenesis through p38 MAPK signaling.

PMID- 21189161
TI  - Epigenetic modification of retinoic acid-treated human embryonic stem cells.
AB  - Epigenetic modification of the genome through DNA methylation is the key to
      maintaining the differentiated state of human embryonic stem cells (hESCs), and
      it must be reset during differentiation by retinoic acid (RA) treatment. A genome
      wide methylation/gene expression assay was performed in order to identify
      epigenetic modifications of RA-treated hESCs. Between undifferentiated and RA
      treated hESCs, 166 differentially methylated CpG sites and 2,013 differentially
      expressed genes were discovered. Combined analysis of methylation and expression
      data revealed that 19 genes (STAP2, VAMP8, C10orf26, WFIKKN1, ELF3, C1QTNF6,
      C10orf10, MRGPRF, ARSE, LSAMP, CENTD3, LDB2, POU5F1, GSPT2, THY1, ZNF574, MSX1,
      SCMH1, and RARB) were highly correlated with each other. The results provided in
      this study will facilitate future investigations into the interplay between DNA
      methylation and gene expression through further functional and biological
      studies.

PMID- 21189162
TI  - Relationships between genetic polymorphisms and transcriptional profiles for
      outcome prediction in anticancer agent treatment.
AB  - In the era of personal genomics, predicting the individual response to drug
      treatment is a challenge of biomedical research. The aim of this study was to
      validate whether interaction information between genetic and transcriptional
      signatures are promising features to predict a drug response. Because drug
      resistance/susceptibilities result from the complex associations of genetic and
      transcriptional activities, we predicted the inter-relationships between genetic
      and transcriptional signatures. With this concept, captured genetic polymorphisms
      and transcriptional profiles were prepared in cancer samples. By splitting ninety
      nine samples into a trial set (n = 30) and a test set (n = 69), the
      outperformance of relationship-focused model (0.84 of area under the curve in
      trial set, P = 2.90 x 10-4) was presented in the trial set and validated in the
      test set, respectively. The prediction results of modeling show that considering
      the relationships between genetic and transcriptional features is an effective
      approach to determine outcome predictions of drug-treatment.

PMID- 21189163
TI  - Analysis of changes in pro (Gadd153) and anti apoptotic (Grp78) gene expression
      after ischemic-reperfusion injury of the small intestine.
AB  - Analysis of changes after ischemia-reperfusion (IR) attack to the small intestine
      leads to multiple organ dysfunction (multiple organ dysfunction syndrome, MODS)
      and the subsequent death of patients is a topic for discussion. IR stress affects
      the endoplasmic reticulum (ER). ER dysfunction induces responses through kinases
      activation that stimulate anti-apoptotic mechanism, for example Grp78 (Bip)
      (Yeung et al., 2008) and pro-apoptotic mechanism, for example, activation Gadd153
      (Chop) (Allyson et al., 2007). We analyzed the impact of IR damage of epithelium
      of the small intestine of rats after 1 h ischemia and subsequent 1 h, 24 h and 30
      days of reperfusion on the level of apoptotic genes expression (Gadd153) and
      (Bip). In this study we used RT-PCR for detection of changes in gene expression.
      Significantly increased levels of mRNA for Gadd153 gene were detected after 1 h
      ischemia and 1 h reperfusion. The mRNA level of Grp78 gene was increased 24 h
      after ischemia comparing with the control groups. After 30 days of reperfusion
      Grp78 was at the level of control groups. Still, it is necessary to analyze the
      changes in the damaged tissue at the molecular level to define possible pathways
      leading to the tissue protection.

PMID- 21189164
TI  - Effect of mineral water from Trencianske Teplice (drinkable source, drill SB-3)
      on lipid peroxidation in vitro.
AB  - Influence of mineral water from Trencianske Teplice (drinkable source) on lipid
      peroxidation processes was determined in model situations under in vitro
      conditions using the brain tissue. The central nervous system was selected
      because it is especially sensitive to the radical-induced damage. In addition,
      there is a high content of polyunsaturated fatty acids in the brain which has a
      low antioxidant capacity and is relatively rich in iron ions--enhancers of lipid
      peroxidation processes. We present the inhibitory effect of the mineral water on
      the intensity of lipid peroxidation in the presence of iron ions. We assume that
      some component or combination of more components of the mineral water may act as
      chelators of iron ions.

PMID- 21189165
TI  - How does pycnogenol(r) influence oxidative damage to DNA and its repair ability
      in elderly people?
AB  - Our purpose in this randomized, double blind, placebo controlled study was to
      find out the possible effect of a polyphenolic pine bark extract, Pycnogenol(r)
      (Pyc) on the level of 8-oxo-7,8-dihydroguanine (8-oxoG) as representative of
      oxidative damage to DNA and on the DNA repair ability of elderly people.
      According to our results, three months of Pyc administration had no effect on the
      level of oxidative damage to DNA or on repair ability, but we found a
      relationship between the level of 8-oxoG and repair ability of DNA in this group.
      To conclude, even if the positive effect of Pyc was not confirmed in the case of
      elderly people it is important to highlight the necessity of further
      investigations about the mechanisms of Pyc acting on different age groups.

PMID- 21189166
TI  - The factors influencing direct spectral fluorimetry of some urine metabolites.
AB  - Urine contains a variety of organic and inorganic chemicals including a number of
      natural fluorophores. Most of them are formed by tryptophan metabolites. But
      there are also metabolites of riboflavin, catecholamines and porphyrins. The
      alternation in the autofluorescence of urine and the alternation in the
      concentration of these substances are developed by both physiological and
      pathological changes such as disorder of body metabolism, dietary intake, age and
      etc. In this work we present fluorescent properties of chosen urine fluorophores 
      i.e. 5-hydroxyindole-3-acetic acid (5-HIAA), indoxyl sulphate (urine indican),
      serotonin (5-HT), vanillylmandelic (VMA) and homovanillic (HVA) acids typical for
      various diseases. Differences of fluorescent parameters of individual
      fluorophores measured in vitro in the water solutions and in natural environment
      of urine are significant and can lead to false results and conclusions.
      Therefore, we present the most common influence that can occur in urine (e.g. pH,
      ionic strength, proteins, and other fluorophores). The aim is to elaborate the
      exact "know-how" for direct complex fluorescent measurement in urine related to
      particular diagnoses.

PMID- 21189167
TI  - Effect of natural polyphenols, pycnogenol(r) on superoxide dismutase and nitric
      oxide synthase in diabetic rats.
AB  - The work is focused on clarifying the impact of diabetes and natural plant
      polyphenols contained in Pycnogenol(r) (PYC) on the activity and synthesis of
      Cu/Zn-SOD and synthesis of nNOS and eNOS in the cerebellum and cerebral cortex in
      rats with induced diabetes. Rats included in the study (n=38) were divided into
      three groups: the controls (C), (n=7), untreated diabetics (D) (n=19) and
      diabetic rats treated with PYC (DP) (n=12). Diabetes significantly decreased
      synthesis, as well as the activity of Cu/Zn-SOD in both studied parts of the
      brain. PYC significantly increased the synthesis of Cu/Zn-SOD but had no effect
      on its activity. Diabetes also reduced the synthesis of nNOS in cerebral cortex
      and administered PYC elevated its amount to the level of controls. In the
      cerebellum, diabetes does not affect the synthesis of nNOS and PYC reduces
      synthesis of NOS. Diabetes as well as PYC had no influence on the synthesis of
      eNOS in both, the cerebellum and cerebral cortex. PYC modulated level of Cu/Zn
      SOD and nNOS in cerebellum and cerebral cortex of diabetic rats, but in a
      different way.

PMID- 21189169
TI  - Hypercholesterolemia, oxidative stress and gender dependence in children.
AB  - Hypercholesterolemia (HCH) is characterized by an increase of the total- and LDL
      cholesterol in serum. In hypercholesterolemia, generally recognized as a risk
      factor of atherogenesis, oxidative stress and oxidatively modified LDL play a
      crucial role. In our study, children with elevated total cholesterol (above 4.5
      mmol/l) were included. Parameters of lipid profile, lipophilic vitamins and
      antioxidants (retinol, alpha-tocopherol, gamma-tocopherol, xantophyll, lycophen
      and beta-carotene) and markers of oxidative damage to lipids (lipoperoxides and 8
      isoprostanes) were evaluated. We found that children with hypercholesterolemia
      have significantly increased parameters of lipid profile and these are gender
      dependent only in HDL-cholesterol (1.27 +/- 0.10 mmol/l in boys vs. 1.53 +/- 0.07
      mmol/l in girls; p<0.05) and TAG (1.63 +/- 0.31 mmol/l in boys vs. 1.08 +/- 0.09
      mmol/l in girls; p<0.05). In addition, children with HCH have decreased total
      antioxidant capacity of serum (TEAC) (about 19.64%, p<0.05) and increased
      lipoperoxides (LP) (about 45.73%, p<0.001). We have revealed statistically
      significant correlations between parameters of lipid profile and lipophilic
      vitamins and antioxidants, as well as between markers of oxidative stress:
      positive correlation between LP and 8-iso (r=0.353, n=33, p<0.05) and negative
      correlations between these parameters and TEAC (r= -0.377, n=33, p<0.05 for LP
      and r= -0.379, n=33, p<0.05 for 8-iso). In conclusion, we confirmed relation
      between hypercholesterolemia and oxidative stress and effect of gender on these
      processes already in childhood. Since the atherosclerotic process begins in
      childhood before clinical symptoms, early detection of hypercholesterolemia and
      oxidative stress is important in later atherosclerosis prevention.

PMID- 21189168
TI  - Characterization of P19 cells during retinoic acid induced differentiation.
AB  - The aim of our study was to characterize mouse embryonal carcinoma (EC) cells P19
      in different stages of retinoic acid induced neurodifferentiation by two methods,
      immunocytochemistry and RT qPCR. The characterization of the cells is crucial
      before any transplantation into any model, e.g. in our case into the mouse brain
      with the aim to treat a neurodegenerative disease. Specific protein markers (MAP
      2, OCT-4, FORSE-1) were detected by immunocytochemistry in the cell cultures. The
      mRNA expression levels of PAX-6, MASH-1, Brachyury, GATA-4 and AFP were
      determined by RT qPCR method. HPRT was used as a housekeeping gene. The degree of
      differentiation can be characterized by expression of analyzed genes. The
      presence of OCT-4 and FORSE-1 proteins in undifferentiated pluripotent cells and
      the presence of dendrite specific MAP-2 in neuroprogenitors was detected. The
      expression levels of PAX-6 and MASH-1 increased and expression of Brachyury
      decreased during the neurodifferentiation process. The expression levels of GATA
      4 and AFP were the highest after induction of differentiation with retinoic acid.
      Detailed characterization of cells before transplantation experiments can
      contribute to better understanding of their effect.

PMID- 21189170
TI  - [Construction and identification of procaryotic expression vector of human NIT1
      gene].
AB  - BACKGROUND: The human FHIT gene at chromosome 3p14.2 is a tumor suppressor gene,
      and its abnormality in structure and function is related to carcinogenesis and
      progression of lung cancer. It is postulated that FHIT and NIT1 likewise
      collaborate in biochemical or cellular pathway in mammalian cells, but their
      molecular mechanisms in lung cancer cell are still unknown. The aim of this study
      is to construct procaryotic expression vector of human NIT1, providing a
      foundation to explore the expression of human NIT1 protein and to study the
      interaction of NIT1 and FHIT genes in lung cancer cell lines. METHODS: The NIT1
      cDNA was acquired by RT-PCR. EcoRI/NotI digested PCR product was directly cloned
      into procaryotic expression vector pET-32a. RESULTS: The sequence of NIT1 cDNA
      clone exactly corresponded with the sequence of NIT1 cDNA in GenBank. The
      expectant fragments of DNA were obtained after recombinant procaryotic expression
      vector was digested by EcoRI and NotI. CONCLUSIONS: The procaryotic expression
      vector of human NIT1 is successfully constructed by RT-PCR and direct clone. It
      provides an important basis to detect the expression of NIT1 protein and to
      further explore the relationship between NIT1 and FHIT genes in oncogenesis and
      development of human lung cancer.

PMID- 21189171
TI  - [Effect of dihydroartemisinin on proliferation of human lung adenocarcinoma cell
      line A549].
AB  - BACKGROUND: Recent researches discovered that artemisinin and its derivatives had
      anti-tumor activity. Dihydroartemisinin is one of the derivatives with higher
      activity. This study is to explore the effect of dihydroartemisinin on the
      proliferation of human lung adenocarcinoma cell line A549, so as to provide
      experimental base for treatment of lung cancer. METHODS: Inhibition of
      proliferation in vitro was measured by MTT assay. The cell growth curve was drawn
      according to cell counts. The population doubling time was counted in logarithmic
      growth phase, DNA contents were measured by flow cytometry. Cell cycles were
      observed at the same time after the treatment. And the nude mice bearing A549
      cancer cells were applied to detect the effect of dihydroartemisinin in vivo.
      RESULTS: Dihydroartemisinin inhibited A549 cell proliferation in a concentration
      dependent manner, after 96h of treatment, the IC50 for dihydroartemisinin
      inhibition of cell number was 0.23MUmol/l. The population doubling time for human
      lung adenocarcinma in the control group was 21.3h and that in the
      dihydroartemisinin group was 38.5h . An highly significant difference was
      observed between the two groups (P < 0.01). Cells in G0 plus G1 were increased
      after the dihydroartemisinin treatment. The tumor inhibiting rate of
      dihydroartemisinin was 54.3% in vivo. CONCLUSIONS: Dihydroartemisinin has marked
      anticancer activity on human lung adenocarcinoma cell line A549 both in vitro and
      in vivo. The inhibition in vitro is related to blockade of G0 and G1 phases.

PMID- 21189172
TI  - [A case-control study on the association between genetic polymorphisms of
      metabolizing enzymes CYP2D6 and susceptibility to lung cancer].
AB  - BACKGROUND: Genetic polymorphism in metabolic enzymes, which are involved in
      metabolism of environmental carcinogens, have been thought to be related to
      susceptibility of lung cancer. The aim of this study is to investigate the
      cytochrome P450 2D6(CYP2D6) genetic polymorphism distribution in Han population
      in Sichuan, China, and to evaluate the relationship between CYP2D6 genetic
      polymorphism and lung cancer susceptibility. METHODS: PCR-RFLP was used to
      identify CYP2D6ch genotypes among 150 patients with primary lung cancer and 152
      healthy controls, in Han population in Sichuan, China, and case-control study was
      used to analyze the relationship between genetic polymorphism and lung cancer
      susceptibility. RESULTS: (1) The distribution frequency of CYP2D6ch C and T
      allele were 39.5% and 60.5% in control group and 46.3% and 53.7% in lung cancer
      group, respectively. There was no significant difference between the two groups
      (P=0.089). (2)The distribution frequency of C/C, C/T and T/T genotypes were
      18.4%, 42.1% and 39.5% in control group, and 22.7%, 47.3% and 30.0% in lung
      cancer group, respectively. No significant difference was found between the two
      groups (P=0.215). (3) The individuals who carried with Non-T/T genotypes had a
      2.084-fold increased risk with squamous cell carcinoma (95%CI 1.024-4.244,
      P=0.043) than those who carried with T/T genotype. (4) The lighter smokers ( < 30
      pack-years) who carried with Non-T/T genotypes had a 2.92-fold increased risk
      with lung cancer (95%CI 1.087-7.828, P=0.033) than those who carried with T/T
      genotype. CONCLUSIONS: CYP2D6ch Non-T/T genotypes are factors associated
      mail:zhouqh@mail.sc.cninfo.net) with increased risk of squamous cell carcinoma
      and also increase risk of lung cancer among lighter smokers.

PMID- 21189173
TI  - [Effects of canstatin gene transfection on growth and apoptosis of lung cancer
      A549 cells and HUV-ECC cells].
AB  - BACKGROUND: Angiogenesis is essential for tumor's growth and metastasis.
      Canstatin, a newly found potent endogenous angiogenesis inhibitor, has drawn
      researcher's attention to its powerful biological activities on endothelial
      cells. The aim of this experiment is to explore the expression and effects of
      canstatin gene in lung cancer A549 cells and HUV-ECC cells. METHODS: Expression
      vector of pCMV- Script/Canstatin was transfected into A549 and ECC cells by
      electroporation, and the positive clone was screened by G418. Growth
      characteristics of the two cell lines were compared before and after
      transfection. Expression of canstatin protein in supernatant was examined by SDS
      PAGE assay, and cell cycles of the two cell lines were analysed by flow
      cytometry. RESULTS: The expression of canstatin gene was found in supernatant of
      the transfected A549 cells and ECC cells. The apoptotic rate in the transfected
      ECC cells (16.04%) was significantly increased compared with that of the naked
      plasmid control group (0.43%) and parental cell group (2.92%) (P < 0.01). The
      growth of the transfected ECC cells was significantly inhibited (P < 0.01). The
      apoptotic rate in the transfected A549 cells (0.19%) showed no marked difference
      from the naked plasmid control group (0.13%) and parental cell group (0.07%) (P >
      0.05). No significant difference in cell growth was found among the transfected
      A549 cell, naked plasmid control and parental cell groups. CONCLUSIONS: The
      results indicate that canstatin gene can express in lung cancer A549 cell line
      and HUV-ECC cell line, and it can specifically inhibit proliferation of
      endothelial cell and induce its apoptosis.

PMID- 21189174
TI  - [Expressions of EphB4 and HIF-1alpha in human lung cancer and their
      significances].
AB  - BACKGROUND: It has been proved that EphB4 and HIF-1alpha are closely related to
      the oncogenesis and development of lung cancer. The aim of this study is to
      investigate the biological significances of EphB4 and HIF-1alpha in lung cancer
      and their relationship with each other. METHODS: The expression of EphB4 and HIF
      1alpha was detected in 54 lung cancer tissues and 10 normal lung tissues as
      control by immunohistochemical method. RESULTS: EphB4 and HIF-1alpha proteins
      were detectable in 50.0% and 42.6% of all 54 lung cancer tissues respectively,
      which were significantly higher than those of the control (P < 0.05); the
      positive ratios and the levels of the expressions of EphB4 and HIF-1alpha
      proteins were closely related to gross types, differentiations and clinical
      stages (P < 0.05), but not to histological classification, age, sex and lymph
      node metastasis (P > 0.05). A highly positive correlation was observed between
      EphB4 and HIF-1alpha expression (P < 0.01 ). CONCLUSIONS: Overexpression of EphB4
      and HIF-1alpha may play an important role in the pathogenesis, progression and
      malignant degree of lung cancer. Detection of EphB4 and HIF-1alpha expression
      might be helpful to predict prognosis of patients with lung cancer.

PMID- 21189175
TI  - [Expressions of connexin 43 and E-cadherin and their correlation in non-small
      cell lung cancer].
AB  - BACKGROUND: Connexin (Cx), a transmembranous protein, makes up of gap junction,
      which induces the communication of cells and plays an important role in
      proliferation and differentiation of cells. The directly or indirectly reduced
      expression of connexin protein may induce a malignant tendency of cells. E
      cadherin is a transmembranous glycoprotein and induces the adhesion of
      epitheliums and extracellular matrix. The reduced expression or dysfunction of E
      cadherin will impair the ability of adhesion and make cells easy to be isolated.
      The aim of this study is to examine the expressions of Connexin 43 (Cx43) and E
      cadherin in non-small cell lung cancer (NSCLC), and to analyze their correlation.
      METHODS: The expressions of Cx43 and E-cadherin proteins were detected in 85
      primary NSCLC samples by immunohistochemistry S-P method, and their correlation
      was then analyzed. RESULTS: The expressions of Cx43 and E-cadherin were
      remarkably decreased in NSCLC tissues. Cx43 and E-cadherin expressions were
      related to cell differentiation, pTNM stage and lymphatic metastasis of NSCLC.
      The expression of Cx43 significantly correlated with the expression of E
      cadherin. CONCLUSIONS: The expressions of Cx43 and E-cadherin significantly
      decrease in NSCLC and they correlate with each other. It might be common affairs
      in carcinogenesis and development of NSCLC.

PMID- 21189176
TI  - [Relationship between genetic polymorphism of GSTT1 gene and inherent
      susceptibility to lung cancer in Han population in Sichuan, China].
AB  - BACKGROUND: Some studies have supposed that glutathione S-transferases (GSTs) may
      be involved in detoxification of carcinogens, especially from tobacco smoke.
      Therefore, polymorphism of GSTs has been considered as potential protectors of
      individual cancer risk. The objective of this study is to investigate the
      relationship between genetic polymorphism of GSTT1 and inherent susceptibility to
      lung cancer in Han population in Sichuan, China. METHODS: A case-control study
      was carried out to compare the distribution frequency of GSTT1 gene polymorphism
      between lung cancer (n=150) and control healthy individuals (n=152) with
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      method and to analyze the relationship between the GSTT1 gene polymorphism and
      smoking and the inherent susceptibility of lung cancer. RESULTS: (1) The
      distribution frequency of GSTT1(-) genotype was 54.7% (82/150) in lung cancer and
      38.2% (58/152) in control group respectively (OR=1.681, 95%CI=1.009- 2.803 ,
      P=0.046); (2) GSTT1(-) genotype remarkably increased the risk of squamous cell
      carcinoma (OR=2.969, 95%CI= 1.511 -5.834, P=0.002) and adenocarcinoma (OR=2.095,
      95%CI=1.060-4.140, P= 0.033 ); (3) In smokers, GSTT1(-) genotype significantly
      increased the risk for lung cancer (OR=4.051, 95%CI=1.959-8.380 , P=0.000); (4)
      In people with GSTT1(-) genotype, smoking markedly increased the risk for lung
      cancer (OR=53.885, 95%CI=11.789-246.302, P=0.000); (5) In heavy smokers (>=20
      packyears), GSTT1(-) genotype could remarkably increase the risk of lung cancer
      (OR=4.296, 95%CI=1.649-11.190, P=0.003). CONCLUSIONS: (1) People with GSTT1(-)
      genotype have significantly increased risk for lung cancer in Han population in
      Sichuan, China, especially for squamous cell carcinoma. (2) GSTT1(-) genotype
      interacts synergistically with smoking on lung cancer risk. The more the
      cigarettes smoke, the higher the risk of lung cancer increases in those people
      who are smokers with GSTT1(-) genotype.

PMID- 21189177
TI  - [Expressions of cyclooxygenase-2 and vascular endothelial growth factor in human
      lung cancer tissue].
AB  - BACKGROUND: Elevated expression of cyclooxygenase-2 (COX-2) has been found to be
      a feature of tumors recently. In this study, the expression and significance of
      COX-2 and vascular endothelial growth factor (VEGF) were explored in the cancer
      tissues of patients with lung cancer. METHODS: Expression of COX-2 and VEGF in
      cancer tissues of 126 lung cancer patients were detected by tissue chip and
      immunohistochemical methods. The relationships among COX-2 expression, survival
      time and the biology beha- vior of lung cancer were analyzed by retrospective
      cohort study. RESULTS: Expression of COX-2 was positive in 86 cases (68.25%). The
      correlation between COX-2 expression and some biology behaviors of lung cancer (T
      stage, N stage and P-TNM stage) was significant in statistics (P < 0.05). High
      expression of VEGF was also found in cancer tissues (98/126, 77.78%). The
      correlation between COX-2 expression and VEGF expression was significant in
      statistics (Chi-Square=6.72, P < 0.05). The survival time of patients with
      positive COX-2 expression and VEGF expression was significantly shorter than that
      without expression (P < 0.05). CONCLUSIONS: High COX-2 and VEGF expressions are
      detected in lung cancer tissue. Each of them is suggested to be an independent
      predictor of survival in survival analysis. COX-2 and VEGF are significant poor
      prognostic factors in the surgically resected lung cancer.

PMID- 21189178
TI  - [Expression of KAI1 protein in tissue microarray and its biological significances
      in patients with lung cancer].
AB  - BACKGROUND: KAI1 is a new identified metastasis-suppressor gene whose expression
      in many types of tumors has been reported. The aim of study is to investigate the
      role of KAI1 protein in development of lung cancer and its values in predicting
      the prognosis of lung cancer. METHODS: The expressions of KAI1 protein were
      detected in benign pulmonary disease tissue, precancerous disease tissue, lung
      cancer tissue and metastatic lung cancer tissue in local lymph node using tissue
      microarray and immunohistochemical method. The relationship between expression of
      KAI1 protein and clinicopathological parameters of patients with lung cancer was
      analyzed by Chi-Square test and Fisher exact test. RESULTS: The positive rate of
      KAI1 expression was 100.0% in 10 cases of benign pulmonary diseases, 66.7% in 12
      cases of precancerous diseases, 24.7% in 89 cases of primary lung cancer and 0 in
      metastatic lung cancer tissue in local lymph node respectively. The KAI1 protein
      expression in primary lung cancer tissues had no remarkable relationship with age
      and gender of the patients and the location of cancer, but had significant
      relationship with the histological type and differentiated degree of tumor, P-TNM
      stages and lymph node metastatic status. CONCLUSIONS: The abnormal expression of
      KAI1 protein may participate in malignant progression of lung cancer. Its
      downregulation may promote the invasion and metastasis of tumor cell. Detection
      of the expression of KAI1 protein may be helpful to predict the prognosis of lung
      cancer.

PMID- 21189179
TI  - [Clinical evaluation of 18F-FDG-SPECT/CT imaging in diagnosis and staging of
      patients with suspected lung cancer].
AB  - BACKGROUND: Correct diagnosis is very important to patients with suspected lung
      cancer. According to the higher 18F-FDG intake of tumor tissues much more than
      normal tissues, this study evaluates the clinical value of 18F-FDG dual-head
      coincidence SPECT/CT in diagnosis of lung cancer. METHODS: Sixty-one patients
      with lung mass underwent 18F-FDG dual-head coincidence SPECT/CT imaging and
      thoracic CT imaging before operation. These imageological results were compared
      with histological examination of lung mass. RESULTS: The sensitivity, specificity
      and accuracy of 18F-FDG-SPECT/CT in differentiating malignant and benign lesions
      were 82%, 87%, 84%, respectively. Compared with thoracic CT imaging, diagnostic
      rate of mediastinal lymphatic metastasis was significantly higher by 18F-FDG
      SPECT/CT (52% vs 81%, P < 0.05) . CONCLUSIONS: Combined functional-anatomical
      image of 18F-FDG-SPECT/CT has potential to improve staging and localizing
      procedures of lung cancer. It is an excellent modality in diagnosis and
      differential diagnosis of lung cancer.

PMID- 21189180
TI  - [The study on improvement of survival for lung cancer surgically intervened in
      PUMC Hospital].
AB  - BACKGROUND: Lung cancer is still the most common cause of cancer death. Although
      it is reported that the 5-year survival rate for lung cancer has been greatly
      increased, surgical results are controversial. The aim of this study is to
      investigate and evaluate the improvement of survival of lung cancer surgically
      intervened in PUMC hospital during the last 15 years. METHODS: From January 1989
      to December 2003, 1574 cases of lung cancer underwent surgical treatment and
      obtained follow-up. The results were retrospectively a- nalysed . All cases in
      this series were divided into two groups according to time, group A (1999-2003)
      and group B (1989-1998), and the differences of survival rate between group A and
      group B were compared. RESULTS: The morbidity and mortality of group A decreased
      significantly when compared to group B (11.2% vs 19.2%, 1.06% vs 1.93%,
      respectively, P < 0.01). However, the 3- and 5-year survival rates had been
      obviously raised from 42.35% to 56.07%, and from 28.46% to 38.99%, respectively
      (P < 0.05 ). A significant improvement in survival was observed in patients with
      stageI, stage II and stage IIIA, but not in stage IIIB and stage IV. Also, the
      patients with lobectomy had better results but those with exploratory
      thoracotomy, limited resection, pneumonectomy and sleeve resection did not show
      better results. CONCLUSIONS: Lobectomy associated with systematic dissection of
      mediastinal lymph nodes has become the standard mode for the resectable lung
      cancer. Combination of complete resection and lymph nodes dissection, with
      postoperative adjuvant chemotherapy based on platinum/3rd generation medicine,
      have preliminarily been justified and proved an important approach for effective
      improvement of long-term survival of lung cancer.

PMID- 21189181
TI  - [Value of video-mediastinoscopy in staging of lung cancer].
AB  - BACKGROUND: Mediastinoscopy has experienced a renaissance due to the introduction
      of neoadjuvant treatment protocols and recognition of the limitations of
      noninvasive mediastinal staging of lung cancer by CT and PET. The aim of this
      study is to determine the value of video-mediastinoscopy in mediastinal staging
      of lung cancer. METHODS: A total of 60 patients who underwent video
      mediastinoscopy for known or suspected lung cancer were retrospectively reviewed.
      There were 52 cervical mediastinoscopies, 2 parasternal mediastinoscopies and 6
      combined procedures. All the patients were found to have enlarged mediastinal
      lymph nodes on radiographic examination of the chest (more than 1.0cm on its
      shortest axis). RESULTS: Of the 60 patients, 42 patients were found with N2 or N3
      disease on video-mediastinoscopy and then were confirmed pathologically. The
      other 18 mediastinoscopy-negative patients underwent thoracotomy for pulmonary
      resection and mediastinal lymph node dissection in the same operative session, in
      which thoracotomy-proven N0 was found in 17 patients, and N2 in 1 patient (false
      negative result by video-mediastinoscopy). The sensitivity, specificity, and
      accuracy of video-mediastinoscopy for mediastinal staging of lung cancer were
      97.7%, 100% and 98.3%, respectively. In the entire group of 60 patients, there
      was 1 complication (1.7%) , and no perioperative death. CONCLUSIONS: Video
      mediastinoscopy is a highly effective and safe procedure. It can be used
      routinely in mediastinal staging of lung cancer.

PMID- 21189182
TI  - [Pulmonary blastoma: a report of five cases and review of the literature].
AB  - BACKGROUND: Pulmonary blastoma is a rare primary malignancy of the lung. It is
      now recognized in two forms: adult type pulmonary blastoma and childhood
      pleuropulmonary blastoma. The clinical characteristics, diagnosis and treatments
      of adult type pulmonary blastoma are discussed in this article. METHODS: The
      clinical records of 5 patients with adult type pulmonary blastoma admitted in
      Cancer Center, Sun Yet-sen University from 1964 to 2004 were analyzed and the
      literature on pulmonary blastoma was reviewed. RESULTS: Three patients were male
      and two were female with the ages ranged from 22 years old to 70. Their symptoms
      consisted mainly of cough, hemoptysis and chest pain. The pulmonary blastomas
      were mainly manifested as a solitary parenchymal mass of the lung on chest
      radiograph and CT. None of these patients was diognosed by fibrobronchoscopy nor
      sputum cytology. Three patients underwent lobectomy, one underwent pneumonectomy,
      and these four patients underwent mediastinal lymph node resection also. The
      fifth one received wedge resection and postoperative chemotherapy. At the end of
      follow-up, three patients died and two was alive, and the survival time was from
      6 months to 11 years. CONCLUSIONS: Pulmonary blastoma is difficult to be
      diagnosed before operation. Surgery is the best therapeutic choice up to now. It
      has poor response to radiotherapy and chemotherapy. The prognosis of patient with
      pulmonary blastoma is variable.

PMID- 21189183
TI  - [VPC regimen combined with whole-brain radiotherapy in the treatment of small
      cell lung cancer with brain metastasis].
AB  - BACKGROUND: The main treatment strategy of cancer patients with brain meta-
      stasis is irradiation, while so far there is few research concerning chemotherapy
      combined with radiotherapy for these patients. The aim of this study is to
      evaluate the therapeutic effect and toxicity of chemotherapy with VPC regimen
      combined with whole-brain radiotherapy (WBRT) in small cell lung cancer (SCLC)
      with brain metastasis. METHODS: A total of 60 SCLC patients with brain metastasis
      received a cycle of VPC regimen (teniposide 60mg/m2 iv on days 1-5, cisplatin
      35mg/m2 iv on days 1-3, semustine 80mg/m2 PO on day 1) every 3-4 weeks. WBRT was
      administered on day 6 of the first cycle of chemotherapy at a dose of 2Gy given
      in 5 fractions per week. Patients with less than 3 brain lesions received WBRT at
      a dose of 30Gy and then small field radiotherapy up to total dose of 50Gy,
      otherwise they received WBRT at a total dose of 40Gy. Response was evaluated by
      brain and chest CT or MRI after WBRT and at least 2 cycles of chemotherapy were
      completed. RESULTS: All the patients completed WBRT combined with chemotherapy.
      Total response rate of primary pulmonary tumor was 46.7%, with 4 cases of CR. The
      objective brain response rate was 60.0%, with 11 cases of CR and 25 cases of PR.
      Symptom relief was observed in all 48 patients with neurological symptoms. Main
      adverse effects were myelotoxicity, nausea/vomiting, constipation and alopecia.
      The follow-up rate was 93.3% with a median survival duration of 11.3 months. The
      1-, 2- and 5-year survival rate was 43.3%, 35.0% and 6.7%, respectively.
      CONCLUSIONS: Chemotherapy combined with WBRT can be safely performed for SCLC
      with brain metastasis and its short-term response is quite satisfactory. It may
      be worthy of further clinical investigation.

PMID- 21189184
TI  - [Clinical analysis of misdiagnosis for lung cancer: a report of 31 cases].
AB  - BACKGROUND: In grass-roots hospitals, the rate of misdiagnosis for lung cancer is
      rather high. The aim of this study is to investigate the reasons of misdiagnosis
      for lung cancer. METHODS: A total of 31 patients with signs out of lung from 1987
      to 2004 were analyzed retrospectively. RESULTS: There were different degrees of
      misdiagnosis in these 31 patients. One half of misdiagnostic reasons were medical
      factors, and the other half were due to patients' carelessness (15 cases/16
      cases, 48%/52%). The medical factors included lack of knowledge of medical
      workers about tumor and limited conditions in grass-roots hospitals. The patient
      factor was mainly that they did not receive medical treatment in time.
      CONCLUSIONS: The key point of reducing the misdiagnostic rate of lung cancer is
      to improve the professional level of medical workers and popularize peoples'
      knowledge about lung cancer.

PMID- 21189185
TI  - Effect of ankle arthritis on clinical outcome of lateral ankle ligament
      reconstruction in cavovarus feet.
AB  - BACKGROUND: Patients with idiopathic cavovarus deformity and lateral ankle
      ligament instability often present with varying degrees of ankle arthritis. The
      purpose of this study was to determine whether the severity of degenerative
      change would impact the clinical outcome in patients treated operatively for both
      cavovarus deformity and lateral ankle ligament instability. MATERIALS AND
      METHODS: Twenty-two patients were treated with lateral ankle ligament
      reconstruction and realignment foot osteotomy. American Orthopaedic Foot and
      Ankle Society (AOFAS) ankle-hindfoot score, Karlsson and Peterson (KP) scoring
      scale, Visual Analog Scale (VAS) for pain, and level of satisfaction were
      obtained. Preoperative and postoperative ankle radiographs were reviewed and
      graded using the van Dijk score. Patients with Grade 0 and I arthritis
      preoperatively were grouped together as ''no to minimal arthritis'' (Group 1) and
      those with Grade II and III arthritis preoperatively as ''moderate to severe
      arthritis'' (Group 2). There were 14 ankles in Group 1 and eight ankles in Group
      2. Mean followup was 60.4 months. RESULTS: Mean AOFAS and KP scores were
      significantly improved in Group 1 compared to Group 2 at latest followup, while
      VAS pain scale trended lower in Group 1. There were 12 excellent/good results,
      one fair result, and one poor result in Group 1. Patients in Group 2 had three
      excellent/good results, two fair results, and three poor results. One of 14
      patients in Group 1 had progression of arthritis, while five of eight patients in
      Group 2 either had progression of arthritis or required an ankle fusion.
      CONCLUSION: Patients treated with lateral ankle ligament reconstruction and
      cavovarus realignment osteotomy with no to minimal preoperative tibiotalar
      arthritis have higher clinical scores and increased satisfaction compared to
      patients with more advanced preoperative tibiotalar arthritis. A cautious and
      realistic approach should be followed when recommending surgical treatment for
      this patient population.

PMID- 21189186
TI  - Painful bone marrow edema syndrome of the foot and ankle.
AB  - BACKGROUND: Bone marrow edema syndrome (BMES) of the foot and ankle is an
      uncommon and often undiagnosed disorder that, to our knowledge, has not
      previously been reported in the orthopaedic literature. The current study reviews
      a consecutive series of patients who were seen with this musculoskeletal disorder
      in order to highlight the clinical presentation and diagnostic imaging
      characteristics specific to this disorder. MATERIALS AND METHODS: A retrospective
      chart study was performed involving 601 patients who underwent magnetic resonance
      (MR) imaging of the foot and ankle at our institution from April 2005 to April
      2006. We identified 14 patients whose MR imaging demonstrated findings consistent
      with BMES. RESULTS: All 14 patients demonstrated characteristic diffuse,
      irregularly increased signal intensity on T2-weighted MR imaging and variable
      areas of decreased signal intensity on T1-weighted MR images in an average of
      three bones within the foot and ankle. Average patient age was 16.4 (range, 10 to
      27) years, and no patient reported a history of prior trauma. Eight patients
      received treatment for an incorrect initial diagnosis with two of those patients
      undergoing surgical procedures. Twelve patients were successfully treated with
      supportive nonoperative therapy for an average length of 19.4 months. Four
      patients had followup MR imaging demonstrating signal changes consistent with
      their clinical improvement/changes. CONCLUSION: BMES of the foot and ankle is a
      clinical disorder seen in younger patients with a clinical history of prolonged
      foot and ankle pain of unknown etiology and without prior trauma. MR findings
      from this series are consistent with previous descriptions in the radiology
      literature. Furthermore, MR imaging can be utilized to monitor the progression or
      resolution of this disorder. Proper diagnosis and treatment may prevent further
      unnecessary diagnostic testing or surgical procedures.

PMID- 21189187
TI  - First ray mobility increase in patients with metatarsalgia.
AB  - BACKGROUND: The significance and measurement of first metatarsal hypermobility
      has been difficult to quantify in relation to transfer metatarsalgia. We
      evaluated the hypothesis that dynamic elevation of the first metatarsal relative
      to the second metatarsal could be measured with a simple device and would be
      associated with transfer metatarsalgia. We also assessed intraobserver and
      interobserver reliability of the simple device. MATERIALS AND METHODS: A series
      of 352 patients were prospectively measured for dynamic metatarsal elevation: 64
      patients with transfer metatarsalgia and 288 patients without symptoms. RESULTS:
      Those with metatarsalgia symptoms had significantly greater first ray mobility (9
      mm versus 7 mm; p < 0.0002) and metatarsal elevation (5 mm versus 3 mm; p <
      0.0002) than patients without symptoms. CONCLUSION: In this prospective series,
      the device was reliable for measuring dynamic first metatarsal elevation at
      different time points with different examiners. Patients with metatarsalgia had
      higher dynamic metatarsal elevation compared to patients without metatarsalgia,
      suggesting a mechanism by which load can be transferred from the first to lesser
      metatarsals.

PMID- 21189188
TI  - Immediate internal fixation of open ankle fractures.
AB  - BACKGROUND: Open ankle fractures are one of the most frequently treated open
      fractures. Immediate internal fixation in open ankle fractures is widely reported
      to produce good results, with a very low infection rate. However, there are few
      reports in the literature discussing distinct features of open ankle fractures.
      Thus, the aim of this study was to explore the injury features of such fractures
      and the operative technique; pilon fractures were excluded. MATERIALS AND
      METHODS: Ninety-six patients with open ankle fractures underwent surgery between
      August 2001 and March 2008. Ninety-two patients were followed for an average of
      35 (range, 14 to 66) months. Intravenous antibiotics were initiated in the
      emergency room, and wounds were copiously irrigated and thoroughly debrided in
      the operating room as soon as possible. Based on the fracture's classification,
      the extent of comminution, and the wound condition, a rational sequence of
      treatment for each malleolar fracture was determined. Reduction and internal
      fixation of the fractures were performed in turn. RESULTS: Primary wound healing
      was achieved in 65 patients. Superficial skin necrosis was seen in 19 patients,
      four patients had delayed wound healing and two had superficial infections. One
      diabetic patient developed a deep infection. The average time of fracture healing
      was 13 weeks. The mean AOFAS ankle-hindfoot score was 90.4 (range, 59 to 100).
      CONCLUSIONS: Compared with closed ankle fractures, open ankle fractures have some
      unique injury features, and correspondingly require special treatment methods
      with respect to soft-tissue handling, restoration of large posterior malleolar
      fractures, the reconstruction sequence of malleolar fractures, and the management
      of distal tibiofibular syndesmotic diastasis.

PMID- 21189189
TI  - Retrograde intramedullary nail arthrodesis for avascular necrosis of the talus.
AB  - BACKGROUND: Avascular necrosis (AVN) of the talus from any etiology is a
      devastating pathology. There are few salvage options available and controversy
      exists as to the surgical management for patients with talar AVN. The authors
      present their results of tibiotalocalcaneal arthrodesis with a retrograde nail.
      MATERIALS AND METHODS: A comprehensive chart and radiographic review was pulled
      from our database for patients with AVN of the talus, who were treated by
      tibiotalocalcaneal fusion with retrograde intramedullary nail. Primary outcome
      was union, with time to clinical union as a secondary endpoint. RESULTS: Fourteen
      patients were included. The average age at surgery was 47.4 +/- 12.8 years, there
      were nine female patients, and the average Body Mass Index was 33.5 +/- 6.0.
      Surgical risk factors included two patients who smoked, one was diabetic, and one
      had a preoperative ulceration. The average time to partial weightbearing was 70.6
      +/- 25.4 days, and the average time to full weightbearing was 100.6 +/- 35.5
      days. Four patients had postoperative complications, while no patients required
      major revision surgery. Twelve patients went on to solid fusion, while two went
      on to a stable, braceable pseudoarthrosis. Eight patients were able to return to
      shoes, and eight were able to walk unaided at final followup. CONCLUSION: Salvage
      of talar AVN is possible by tibiotalocalcaneal arthrodesis with an intramedullary
      nail. Physicians may offer this as a salvage option to patients with a high
      likelihood of successful fusion.

PMID- 21189190
TI  - One stage resection and pin stabilization of first metatarsophalangeal joint for
      chronic plantar ulcer with osteomyelitis.
AB  - BACKGROUND: Standard treatment of plantar first metatarsal head neuropathic
      ulceration with underlying osteomyelitis consists of extensive debridement of
      infected soft tissues and bone and often first ray amputation. The purpose of
      this study was to present a previously unreported, one stage, alternative to
      first ray amputation in patients with chronic first metatarsal head ulceration
      and associated chronic osteomyelitis. MATERIALS AND METHODS: A retrospective
      review was conducted of all patients that underwent one stage resection of the
      first metatarsophalangeal joint with pin stabilization for treatment of chronic
      plantar first metatarsal head ulceration with associated chronic osteomyelitis.
      The study included 15 patients (18 feet) who underwent 18 resections and
      stabilizations. All patients had a diagnosis of diabetic peripheral neuropathy,
      chronic plantar first metatarsal head ulceration of at least 3 months duration
      with exposed bone, and no gross purulence or acute cellulitis. Nine patients
      (60%) (11 feet) were available for followup telephone interviews. Four of the 15
      (27%) (four feet) were deceased so they had medical record review only. The
      average followup was 48.8 months. RESULTS: All ulcers healed with the exception
      of one foot (5%) who required a transmetatarsal amputation for worsening
      infection and wound complications. Three feet (17%) developed recurrent
      ulcerations. No foot had amputation of only the hallux or first ray. CONCLUSION:
      This study presents a previously unreported, relatively simple, one stage
      treatment option for chronic first metatarsal head ulceration with underlying
      chronic osteomyelitis. This procedure allowed for successful healing of the ulcer
      while retaining the first ray.

PMID- 21189191
TI  - Plantar loading after chevron osteotomy combined with postoperative physical
      therapy.
AB  - BACKGROUND: Recent pedobarographic studies have demonstrated decreased loading of
      the great toe region and the first metatarsal head at a short- and intermediate
      term followup. The purpose of the present study was to determine if a
      postoperative rehabilitation program helped to improve weightbearing of the first
      ray after chevron osteotomy for correction of hallux valgus deformity. MATERIALS
      AND METHODS: Twenty-nine patients with a mean age of 58 years with mild to
      moderate hallux valgus deformity who underwent a chevron osteotomy were included.
      Postoperatively, the patients received a multimodal rehabilitation program
      including mobilization, manual therapy, strengthening exercises and gait
      training. Preoperative and one year postoperative plantar pressure distribution
      parameters including maximum force, contact area and force-time integral were
      evaluated. Additionally the AOFAS score, ROM of the first MTP joint and plain
      radiographs were assessed. The results were compared using Student's t-test and
      level of significance was set at p < 0.05. RESULTS: In the great toe, the mean
      maximum force increased from 72.2 N preoperatively to 106.8 N 1 year after
      surgery. The mean contact area increased from 7.6 cm(2) preoperatively to 8.9
      cm(2) 1 year after surgery and the mean force-time integral increased from 20.8
      N(*)sec to 30.5 N(*)sec. All changes were statistically significant (p < 0.05).
      For the first metatarsal head region, the mean maximum force increased from 122.5
      N preoperatively to 144.7 N one year after surgery and the mean force-time
      integral increased from 42.3 N(*)sec preoperatively to 52.6 N(*)sec 1 year
      postoperatively (p = 0.068 and p = 0.055, respectively). The mean AOFAS score
      increased from 61 points preoperatively to 94 points at final followup (p <
      0.001). The average hallux valgus angle decreased from 31 degrees to 9 degrees
      and the average first intermetatarsal angle decreased from 14 degrees to 6
      degrees (p < 0.001 for both). CONCLUSION: Our results suggest that postoperative
      physical therapy and gait training with a Chevron osteotomy may help to improve
      weightbearing of the great toe and first ray. Therefore, we believe there is a
      restoration of more physiological gait patterns in patients who receive this
      postoperative regimen.

PMID- 21189192
TI  - Arterial anatomy of the talus: a cadaver and gadolinium-enhanced MRI study.
AB  - BACKGROUND: Avascular necrosis following a fracture of the talar neck may be
      secondary to the injury itself, or may result from the surgical approach and
      exposure during treatment. We sought to define the arterial anatomy of the talus
      using gadolinium-enhanced magnetic resonance imaging (MRI) and through gross
      dissection following latex injection of cadaver limbs. The use of gadolinium
      enhanced MRI for the evaluation of the arterial supply of the talus has not been
      previously reported. METHODS AND MATERIALS: We utilized 12 fresh frozen cadaver
      limbs to study the arterial anatomy of the talus. The anterior tibial, posterior
      tibial, and peroneal arteries were isolated and cannulated with polyethylene
      catheters. Gadolinium was injected into the cannulas, and conventional MRI
      sequences including suppressed and unsuppressed 3D gradient echo sequences
      obtained. Following MRI, latex was injected into the cannulas and gross
      dissection performed. In addition, the vascular constraints to anteromedial and
      anterolateral approaches to the talus were defined. RESULTS: MRI proved useful in
      the present study to confirm the presence of specific arterial branches in situ,
      as well as to demonstrate the rich anastomotic network in and around the talus. A
      branch to the medial talar neck that has not been previously identified is
      described which was found in nine of the specimens. This newly described branch
      to the medial talar neck was consistently noted to be lacerated following a
      standard anteromedial approach to the talus. CONCLUSION: The use of gadolinium
      enhanced MRI provided very detailed images demonstrating a rich and complex
      anastomotic arterial network that surrounds and perforates the talus. CLINICAL
      RELEVANCE: A thorough understanding of the anatomy and meticulous dissection are
      essential to prevent unnecessary further injury to the vasculature when treating
      fractures of the talus.

PMID- 21189193
TI  - Plantar pressure during running in subjects with chronic ankle instability.
AB  - BACKGROUND: It has been suggested that dynamic foot and ankle mechanics
      predispose individuals with CAI to repetitive episodes of the ankle ''giving
      way.'' Plantar pressure variations during a walking gait have been detected in
      those with CAI, but more dynamic conditions for analysis are needed. The purpose
      of this study was to evaluate plantar pressure distributions during a running
      gait in individuals with CAI, individuals who suffered a lateral ankle sprain,
      but did not develop CAI (AS), and subjects with no history of a lateral ankle
      sprain (CON). MATERIALS AND METHODS: Forty-five subjects [15 in each group,
      healthy males (18) and females (27), age 18 to 45] were recruited from University
      communities to participate in this study. Plantar pressure distributions were
      analyzed on a Tekscan(c) plantar pressure mat at 66 frames per second during a
      running gait at a controlled speed. The following variables were obtained:
      rearfoot medial/lateral (M/L) pressure ratio at foot strike (FS) and center-of
      pressure (COP) trajectory during the initial loading response (heel strike to
      initial peak GRF). Separate one-way ANOVA with Tukey's post-hoc were used to test
      for group differences. The significance level was defined as p < 0.05. RESULTS:
      The CAI group had a significantly more lateral ratio (0.97 +/- 0.12) at FS when
      compared to the CON (1.01 +/- 0.13) and AS (1.11 +/- 0.13) groups. The CAI
      subjects had a lateral COP trajectory during the loading phase (7.97 degrees +/-
      11.02), while both the AS (-3.68 degrees +/- 10.24) and CON groups (-6.27 degrees
      +/- 9.86) had medial trajectories. The difference was significant between the CAI
      group and both the AS and CON groups (all significant {?it p} values were less
      than 0.05). CONCLUSION: Our results confirm that CAI subjects have a more lateral
      foot positioning and loading pattern during a barefoot running gait when compared
      to both the CON and LAS groups. CLINICAL RELEVANCE: Clinicians treating patients
      with CAI should consider providing interventions to decrease the amount of
      rearfoot inversion at FS and during loading in order to create a more medial COP
      trajectory upon impact.

PMID- 21189194
TI  - Accuracy of medial foot compartment pressure testing: a comparison of two
      techniques.
AB  - BACKGROUND: Foot compartment syndrome is diagnosed with intracompartmental
      pressure measurements. The purpose of this study was to determine the ability of
      two techniques to accurately place a needle tip within the medial foot
      compartment and to compare the proximity of the needle tip to the medial foot
      compartment neurovascular structures between the two techniques. MATERIALS AND
      METHODS: This was a laboratory study using ten unembalmed cadaveric ankle-foot
      specimens. Two 18-gauge side-ported needles were placed into the medial foot
      compartments of each cadaveric specimen utilizing two separate techniques
      (Mollica and Reach techniques). Ultrasound was used to confirm needle tip
      placement within the medial foot compartment and needle proximity to the
      neurovascular structures. RESULTS: Both needle placement techniques accurately
      placed the needle tip within the medial foot compartment. However, the distance
      between the needle tip and the neurovascular structures of the medial foot
      compartment was significantly closer (p = 0.037) using the Mollica technique
      (mean = 3.9 mm +/- 2.2 mm) than the Reach technique (mean = 10.9 mm +/- 5.2 mm).
      Neither needle placement technique perforated the medial foot neurovascular
      structures. CONCLUSION: While both medial foot compartment pressure techniques
      accurately placed the needle tip within the medial foot compartment, the needle
      tip was significantly further from the medial foot neurovascular structures using
      the Reach technique than the Mollica technique. The Reach technique involves
      inserting the needle 6 cm below the distal tip of the medial malleolus, and
      advancing it 1 cm in a medial to lateral direction.

PMID- 21189195
TI  - Over-the-top knot placement technique enhances tensile stability of tendon
      repairs.
AB  - BACKGROUND: Currently a major concern for the surgical treatment of Achilles
      tendon rupture repairs is the creation of stable enough fixation to allow early
      range of motion. It was documented that the weakest point in a suture loop is the
      knot. Thus, we hypothesized that moving the knot away from the repair junction
      (over-the-top Krackow technique) would increase the strength of the repair.
      MATERIALS AND METHODS: Transected bovine tendons were repaired by the traditional
      Krackow and over-the-top Krackow techniques using four suture materials
      (Fiberwire Nos. 5 and 2, Ethibond Nos. 5 and 2). Tendons were cyclically tested
      at incremental loads beginning from 50 N until 5-mm gap formation. Then all
      tendons were loaded to failure. The number of cycles to 5-mm gapping, ultimate
      failure loads and knot slip were compared using t-test and Mann-Whitney tests
      (with Tukey corrections for multiple comparisons). RESULTS: Mean number of cycles
      to 5-mm gapping did not reveal significant differences (p = 0.113) between repair
      groups. Mean failure load of tendons repaired by over-the-top Krackow technique
      were significantly higher (p < 0.0001) for all four paired groups than tendons
      repaired by traditional Krackow technique. Ethibond No. 5, No. 2, and Fiberwire
      No. 2 suture repairs with over-the-top configuration did not reveal any knot
      slip. CONCLUSION: Over-the-top Krackow technique increases the ultimate failure
      load of repaired tendons. But 5-mm gapping resistivity was not enhanced either by
      the technique or the suture material. CLINICAL RELEVANCE: The knot itself is a
      stress-riser in the suture loop so we suggest that freeing it from tension by our
      modificiation may achieve more durable repairs.

PMID- 21189196
TI  - Effect of heel lifts on plantarflexor and dorsiflexor activity during gait.
AB  - BACKGROUND: Previous investigators have shown that high heels decrease the muscle
      activity of the gastrocnemius muscle during gait. However, it is not known
      whether commonly used in-shoe heel lifts of lower heights will demonstrate
      similar effects on muscle activity. The aim of this study was to determine
      whether heel lifts alter the muscle activity of the ankle plantarflexors and
      dorsiflexors during the stance phase of gait among individuals with limited
      gastrocnemius extensibility. MATERIALS AND METHODS: This study used a repeated
      measures design. Twenty-four healthy volunteers (12 males and 12 females) with
      less than 5 degrees of passive ankle dorsiflexion with the knee extended
      participated in the study. Electromyography (EMG), computerized motion analysis,
      and a force plate were used to measure mean muscle activity of the lateral
      gastrocnemius, medial gastrocnemius, soleus and tibialis anterior muscles during
      the stance phase of gait across three walking conditions. Muscle activity was
      measured as participants ambulated at a self-selected speed in athletic shoes
      alone and with heel lifts of 6 mm and 9 mm inserted in athletic shoes. RESULTS:
      Between heel-strike and heel-off, the mean EMG amplitude of the medial
      gastrocnemius increased with both 6 and 9 mm heel lifts and the amplitude of the
      tibialis anterior increased with 9 mm heel lifts compared to shoes alone. Between
      heel-strike and heel-off, there were no significant differences in mean EMG
      amplitude of the lateral gastrocnemius or soleus muscles walking in heel lifts
      compared to shoes alone. Between heel-off and toe-off, there were no significant
      differences in mean EMG amplitude of the lateral gastrocnemius, medial
      gastrocnemius, soleus, or tibialis anterior muscles when walking in heel lifts
      compared to shoes alone. CONCLUSION: Heel lifts increase muscle activity of the
      medial gastrocnemius and tibialis anterior muscles between heel-strike and heel
      off among individuals with limited gastrocnemius extensibility. CLINICAL
      RELEVANCE: We were unable to confirm a decrease in muscle activity when using
      heel lifts.

PMID- 21189197
TI  - Dorsal opening wedge osteotomy of second proximal phalanx for second MTP
      dorsiflexion.

PMID- 21189198
TI  - Arthroscopic fixation technique for osteochondral lesions of the talus.

PMID- 21189199
TI  - Technical tip: use of the Kerrison rongeur through a single-incision exposure for
      resection of Haglund's deformity.

PMID- 21189200
TI  - FootForum: PMN and 510K.

PMID- 21189201
TI  - Symposium: evidence-based medicine: what is it and how should it be used?
      Introduction.

PMID- 21189203
TI  - Continuous infusion versus single bolus popliteal block following major ankle and
      hindfoot surgery: a prospective, randomized trial.
AB  - BACKGROUND: Popliteal sciatic nerve blockade is a commonly used technique
      employed in the management of postoperative pain following foot and ankle
      surgery. Recent studies have shown that for outpatient surgery, for moderately
      painful procedures, a continuous infusion of local anesthesia via an in-dwelling
      catheter for 48 to 72 hours leads to reduced opiate analgesic requirements and
      improved pain and patient satisfaction scores. MATERIALS AND METHODS: A
      prospective, randomized, double blind, placebo-controlled trial of a continuous
      infusion of bupivacaine verses normal saline via a popliteal catheter after a
      single bolus popliteal block for 72 hours after major ankle and hind foot surgery
      was performed in 54 patients. RESULTS: The average pain scores overall were low
      (range, 1.1 to 3.6 on a Visual Analogue Scale of 0 to 10) throughout the study
      period. Statistically significantly lower pain scores with significantly less
      requirement for supplementary opiate analgesic agents were seen in the treatment
      group. CONCLUSION: Despite the statistically significant findings, with such low
      pain scores in both groups, we believe it remains debatable whether the extra
      time and cost involved warrants the use of a continuous popliteal blockade over a
      single bolus injection.

PMID- 21189204
TI  - Total ankle arthroplasty outcome comparison for post-traumatic and primary
      osteoarthritis.
AB  - BACKGROUND: Mobile-bearing total ankle arthroplasty designs have achieved good
      clinical results for the treatment of ankle osteoarthritis. However, no direct
      comparison of the outcomes of total ankle arthroplasty has been made between post
      traumatic and primary osteoarthritis. The purpose of the present study was to
      compare the clinical and radiographic outcomes of total ankle arthroplasty in
      patients with post-traumatic and primary osteoarthritis. MATERIALS AND METHODS:
      The HINTEGRA total ankle arthroplasty was carried out in 65 patients (67 ankles)
      with symptomatic ankle osteoarthritis. Group A included 37 patients (37 ankles)
      with post-traumatic osteoarthritis, whereas Group B included 28 patients (30
      ankles) with primary osteoarthritis. Patients were assessed clinically and
      radiographically at a mean followup of 38 months. RESULTS: No significant
      differences were found between the two study groups in terms of American
      Orthopaedic Foot and Ankle Society ankle-hindfoot scales, range of motion, or
      radiographic values at final followup (p > 0.05). The incidence of complications
      (38% in Group A, 27% in Group B) and additional procedures (54% in Group A, 27%
      in Group B) was significantly higher in Group A (p = 0.014 for complications, p =
      0.013 for additional procedures). One ankle was revised in Group A for a deep
      infection. CONCLUSION: The clinical and radiographic outcomes of total ankle
      arthroplasty for post-traumatic and primary osteoarthritis were comparable,
      although the incidence of complications after total ankle arthroplasty was higher
      in the post-traumatic osteoarthritis group. More preceding or concomitant
      surgeries were required in order to make the post-traumatic cases suitable for
      total ankle arthroplasty.

PMID- 21189205
TI  - Surgical management and treatment algorithm for the subtle cavovarus foot.
AB  - BACKGROUND: Subtle cavovarus foot is a condition that can lead to significant
      foot pain and disability. We review the results of our treatment algorithm at
      medium-term followup. MATERIALS AND METHODS: Thirty-five consecutive patients
      with lateral based symptoms due to an underlying congenital subtle cavovarus foot
      type were surgically corrected. Various procedures were utilized, including some
      combination of the following: lateral displacement calcaneus osteotomy, peroneus
      longus to brevis transfer, dorsiflexion first metatarsal osteotomy, and Achilles
      tendon lengthening. Twenty-three patients, with 29 feet, returned for followup
      examination. The mean patient age at the time of surgery was 43.4 years, and the
      mean followup to date was 4.4 years. RESULTS: The mean AOFAS ankle hindfoot score
      preoperatively was 45, and postoperatively was 90. Radiographically, the medial
      cuneiform to floor height changed from 3.5 cm preoperatively to 3.0 cm
      postoperatively. The talo-first metatarsal angle improved 7.5 degrees
      postoperatively. There were no nonunions. No patients to date have gone on to
      fusions or revisions. Ten feet (34%) required hardware removal. All patients had
      resolution of their symptoms following hardware removal. CONCLUSION: The surgical
      management for the subtle cavovarus foot based on the proposed treatment
      algorithm provided symptomatic relief, longstanding correction, and high patient
      satisfaction.

PMID- 21189206
TI  - Total ankle replacement outcome in low volume centers: short-term followup.
AB  - BACKGROUND: The indication for total ankle replacement (TAR) as an alternative to
      ankle fusion continues to be a much-debated topic. The reported survival of TAR
      at midterm followup is approximately 90%. The aim of this study was to compare
      functional outcome and survival of TAR in low volume centers versus high volume
      centers. MATERIALS AND METHODS: A retrospective cohort study was carried out in
      four low volume centers. Sixty-four Salto TARs were performed between 2003 and
      2007 in 60 patients. Fifty-five (59 TAR) patients were eligible for followup with
      28 men. Standardized American Orthopaedic Foot and Ankle Society (AOFAS) scores,
      patient satisfaction, and range of motion (ROM) were measured. Standardized and
      dynamic radiographs were used for evaluation of radiolucencies, ROM and component
      alignment. RESULTS: Seven of the 59 ankle prostheses had to be revised: five for
      loosening and two for deep infection. Three of the five revised for loosening
      went on to fusion, and in two a revision of one of the components was performed.
      Both infected ankles were fused. Five patients declined to participate this
      study, among these two were TAR failures. Survival with revision as the endpoint
      was 86% at final followup. The average AOFAS score was 75 (SD +/- 15). On dynamic
      radiographs the ROM was 22 degrees (SD +/- 8) in the tibiotalar joint.
      CONCLUSION: This study demonstrated that functional results of total ankle
      replacement in low volume centers were comparable to most high volume centers but
      survival was lower especially when we consider our shorter followup than most
      comparable series.

PMID- 21189207
TI  - Intraoperative ultrasonography during percutaneous Achilles tendon repair.
AB  - BACKGROUND: The purpose of the study was to determine whether real-time
      intraoperative ultrasonography improved implant positioning and stump
      approximation in patients with acute Achilles tendon rupture managed
      percutaneously. MATERIALS AND METHODS: The needles were introduced percutaneously
      without ultrasonography and their position was checked relative to cutaneous
      landmarks and by palpation. Then, intraoperative ultrasonography was performed to
      assess needle position at the proximal tendon segment, tendon tear, and distal
      tendon segment. Incorrectly placed needles were removed and reinserted under real
      time ultrasonographic guidance. Tendon apposition was checked
      ultrasonographically. RESULTS: We included 21 patients (19 males, two females)
      with unilateral acute Achilles tendon rupture, in whom 42 needles (one medial and
      one lateral) were inserted. Correct positioning was achieved without
      ultrasonographic guidance for 19 (45%) needles overall, 15 of 21 (71%) medial
      needles, and four of 21 (19%) lateral needles. The remaining 23 needles were
      correctly repositioned under ultrasonographic guidance. The correct positioning
      rates with and without ultrasonography differed significantly for all needles (p
      < 0.0001) and for lateral needles (p < 0.0001) but not for medial needles (p =
      0.03). Intraoperative ultrasonography confirmed tendon stump approximation in all
      cases. CONCLUSION: Without imaging, 55% of needles were correctly positioned.
      Intraoperative ultrasonography allowed correct positioning of all needles and
      provided intraoperative confirmation of stump approximation.

PMID- 21189208
TI  - Comparison of different outcome instruments following foot and ankle trauma.
AB  - BACKGROUND: Identifying optimal treatment strategies in patients with traumatic
      foot and ankle injuries has been hampered by the use of multiple available
      outcome measures with unproven reliability and validity. This prospective
      observational study aimed to measure the correlation between six functional
      outcome measures in patients with traumatic foot and ankle injuries. MATERIALS
      AND METHODS: Patients 18 years of age or older with a traumatic foot or ankle
      injury completed the Short Form-12 (SF-12), Short Musculoskeletal Functional
      Assessment (SMFA), Foot Function Index (FFI), Foot and Ankle Ability Measure
      (FAAM), American Academy of Orthopedic Surgeons (AAOS), Foot and Ankle
      Questionnaire and American Orthopedic Foot and Ankle Society (AOFAS) Ankle
      Hindfoot Scale at a single followup visit. Raw scores for each of the outcome
      measures were calculated. Fifty-two patients were enrolled in our study. Pearson
      correlation coefficients provided measures of correlation. RESULTS: Moderate to
      strong correlations were found for most pairwise comparisons of raw scores and
      functional categorical rankings (rho=|0.5243 to 0.92|, p < 0.002). The strongest
      correlations were found between the SMFA, FFI, FAAM and AAOS Foot and Ankle
      Questionnaire. CONCLUSION: High correlations between scores on six commonly used
      functional outcome instruments suggest it is likely unnecessary to use more than
      one instrument when examining functional outcome in patients with traumatic foot
      and ankle injuries. However, inconsistencies between measures in the same patient
      population suggest a need for further validation and scrutiny.

PMID- 21189209
TI  - Estrogen receptor expression in posterior tibial tendon dysfunction: a pilot
      study.
AB  - BACKGROUND: The pathophysiology of posterior tibial tendon dysfunction (PTTD) is
      poorly understood. It has been theorized that changes in hormone physiology may
      be a factor influencing tendon health. Estrogen's influence on the fibroblast has
      been studied in other musculoskeletal tissues. Gender differences in anterior
      cruciate ligament (ACL) injuries have been studied and it has been discovered
      that the Estrogen receptor (ER) as well as Progesterone receptor (PR) are
      expressed in the ACL. MATERIAL AND METHODS: Eight patients with PTTD requiring
      surgery were enrolled in our pilot study. The mean patient age was 52.4 (range,
      18 to 73) years. There were five female and three male patients. Tendon samples
      were harvested from diseased PTT. Tendon samples harvested from healthy PTT and
      healthy flexor digitorum longus (FDL) tendon were used as controls. Tendon
      samples were processed using specific protocols for total RNA isolation from
      hypocellular, dense connective tissues. ERalpha and ERbeta transcripts were
      quantified using real time RT-PCR. Quantitative values were obtained from the
      threshold cycle (Ct) number at which the increase in fluorescent signal
      associated with an exponential increase of PCR products can be detected. RESULTS:
      Transcripts of both ERalpha and ERbeta were reproducibly detected in RNA samples
      isolated from our tendon samples. There was no difference in receptor expression
      between diseased and control tendon samples. There was no difference in receptor
      expression between male and female patients. CONCLUSION: We found that the
      tenocyte of the PTT and FDL tendons express ERalpha and ERbeta. Normal and
      diseased tendons of both male and female patients expressed both estrogen
      receptors. CLINICAL RELEVANCE: Identifying ERalpha and ERbeta gene expression in
      the fibroblast was an initial step in discovering whether tenocytes are targets
      for estrogen function. Estrogen receptors were identified indirectly by measuring
      receptor gene expression but we were unable to show a significant difference
      between diseased and control tendons.

PMID- 21189210
TI  - Tibiotalocalcaneal arthrodesis with a curved, interlocking, intramedullary nail.
AB  - BACKGROUND: Tibiotalocalcaneal fusion with a straight rod has a risk of damaging
      the lateral plantar neurovascular structures and may interfere with maintaining
      normal heel valgus position.We report the results of a prospective study of
      tibiotalocalcaneal (TTC) arthrodesis with a short, anatomically curved
      interlocking, intramedullary nail. MATERIAL AND METHODS: Forty-five arthrodesis
      in 42 patients, performed between Jan 2003 and Oct 2008, were prospectively
      followed. The mean followup was 48 (range, 10 to 74) months. The main indications
      for the procedure were failed ankle arthrodesis with progressive subtalar
      arthritis, failed ankle arthroplasty and complex hindfoot deformity. The outcome
      was measured by a combination of pre and postoperative clinical examination,
      AOFAS hindfoot scores, SF-12 scores and radiological assessment. RESULTS: Union
      rate was 89% (40/45). Eighty-two percent (37/45) reported improvement in pain and
      73% (33/45) had improved foot function. Satisfactory hindfoot alignment was
      achieved in 84% (38/45). Postoperatively there was a mean improvement in the
      AOFAS score of 37. Complications included a below knee amputation for persistent
      deep infection, five nonunions, and three delayed unions. Four nails, six
      proximal and six distal locking screws were removed for various causes. Other
      complications included two perioperative fractures, four superficial wound
      infections and one case of lateral plantar nerve irritation. CONCLUSION: With a
      short, anatomically curved intramedullary nail, we had a high rate of
      tibiotalocalcaneal fusion with minimal plantar neurovascular complications. We
      believe a short, curved intramedullary nail, with its more lateral entry point,
      helped maintain hindfoot alignment.

PMID- 21189211
TI  - Effect of ankle flexion angle on axial alignment of total ankle replacement.
AB  - BACKGROUND: The Salto Talaris Anatomic(r) (Tornier) total ankle replacement (TAR)
      has found widespread use in the United States and features rotationally mobile
      trial components that auto-align the final components, which themselves are
      rotationally fixed and highly congruent. Based on recent work on prosthetic and
      native ankle kinematics, we investigated the influence of the ankle flexion angle
      at the time of final component preparation on the axial alignment of the Salto
      Talaris TAR. MATERIALS AND METHODS: Following a power analysis based on a
      clinically meaningful difference of five degrees, eight fresh-frozen cadaveric
      thigh-to-foot specimens underwent installation of trial components using the
      Salto Talaris TAR system. Specimens were cycled from maximal dorsiflexion (DF) to
      plantarflexion (PF), as called for in the surgical technique guide, and drilling
      for the final component was carried out in both five degrees of DF and 15 degrees
      of PF using separate drill holes. These were compared with a reference drill hole
      previously placed along the axis of distal tibial cutting guide. Data were
      analyzed to determine whether components prepared in DF differed from those
      prepared in PF with respect to median (and variance) rotation. RESULTS: We found
      no significant difference in median axial alignment (p = 0.139) or in variances
      between the two groups (p=0.937). CONCLUSION: The ankle flexion angle at the time
      of final component preparation did not significantly alter the axial alignment of
      the Salto Talaris TAR. CLINICAL RELEVANCE: Therefore, the rotational alignment of
      the tibial component is determined by the tibial bone cuts and will not auto
      align to the rotation of the talar component.

PMID- 21189212
TI  - Ankle taping can improve proprioception in healthy volunteers.
AB  - BACKGROUND: Taping is a common technique to treat inversion ankle sprains, but
      the effects of tape on proprioception are still not clear. The purpose of this
      study was to establish whether proprioception would be modified by the use of
      ankle tape. To do so we studied joint position sense (JPS) in healthy volunteers
      using three-dimensional (3D) movement analysis systems. MATERIAL AND METHODS:
      Forty healthy volunteers (mean age and SD = 23.2 +/- 4.2) were asked to actively
      reproduce four different ankle positions: 10 degrees of dorsiflexion, neutral, 10
      degrees and 20 degrees of plantarflexion. The absolute difference between the
      estimated angle and the target angle was used to assess JPS. This difference was
      named Error. Subjects were randomly assigned to the control (n = 21) or the
      intervention (n = 19) groups. Members of the intervention group received ankle
      tape for a lateral ligament sprain in the non-dominant leg. A t-test was used to
      evaluate the results. RESULTS: Tape significantly improved JPS for the
      dorsiflexion position (p = 0.038). Neutral was the most accurately reproduced
      position, and the remaining positions were overestimated for both groups.
      CONCLUSION: Taping improved proprioception in healthy volunteers, and 3D movement
      analysis was a useful method to accurately quantify joint position sense.
      CLINICAL RELEVANCE: Because ankle proprioception is critical to the functional
      success of surgical and rehabilitation treatments, these results regarding
      proprioception are of particular importance because ankle taping is often used in
      preventing ankle sprains and it is a common treatment after ankle injuries.

PMID- 21189213
TI  - Core weave versus Krackow technique for Achilles tendon repair: a biomechanical
      study.
AB  - BACKGROUND: The Krackow stitch, commonly used for Achilles tendon repair, leaves
      the bulk of the stitch on the surface of the tendon as a possible nidus for
      adhesion. The proposed core weave stitch leaves a minimal amount of suture
      material on the tendon surface. The functional strength of the core weave stitch
      compared with the Krackow and the optimal number of throws, or stitches crossing
      the surface of the tendon, with this stitch are not known. MATERIALS AND METHODS:
      Twenty-one matched pairs of fresh-frozen cadaveric Achilles tendons were
      transected and randomly assigned to receive a 4-stranded stitch, either Krackow
      or core weave, with three, five, or seven throws. The samples were cyclically
      loaded to 75, 125 and 175 N for 1000 cycles at each load until failure, defined
      as 5 mm of elongation. RESULTS: No significant difference in failure load was
      observed between the Krackow and core weave groups at any number of throws or
      within the groups based on number of throws. Failure load for the different
      number of throws in the Krackow group approached significance (p = 0.10), with
      higher failure load with three throws. CONCLUSION: Functional strength of the
      core weave stitch and the Krackow stitch did not differ between groups with
      three, five, and seven throws. There was no significant difference in strength
      based on throws in either group. CLINICAL RELEVANCE: The proposed core weave
      stitch provides functional strength similar to that of the Krackow stitch for
      tendon repair with reduced suture material on the tendon surface.

PMID- 21189214
TI  - Avascular necrosis of the talus in a HIV-infected patient.

PMID- 21189215
TI  - Bilateral congenital absence of the anterior tibialis tendon: case report.

PMID- 21189216
TI  - Late intratendinous abscess of the Achilles tendon complicating surgical repair:
      a case report.

PMID- 21189217
TI  - Intoeing Harris view for accessory navicular visualization and hindfoot
      alignment: technique tip.

PMID- 21189218
TI  - Technique tip: open ankle athrodesis using locking compression plate combined
      with anterior sliding bone graft.

PMID- 21189219
TI  - The development of anti-inflammatory drugs for infectious diseases.
AB  - Traditionally, disease is thought to result from an insufficient response of the
      host to infection, leading to increased replication of microorganisms and
      consequently disease. However, infection may not necessarily lead to disease and
      disease is not only the result of uncontrolled replication of a microorganism.
      Indeed, the inflammatory response triggered by certain infections is frequently
      the cause of tissue damage and death. The present review argues that it is
      possible to separate mechanisms necessary for the host response to deal with
      infection from those which cause unwanted inflammation and drive disease. By
      understanding mechanisms which drive disease and where/how interaction leads to
      disease, we may be able to devise novel therapies to alleviate suffering of
      patients. Below, we will describe three situations--influenza, dengue and sepsis-
      in which unwanted (excessive, misplaced or altered) inflammation is responsible
      for disease induction. In these three situations, we will also describe some
      examples of molecules which have been found to drive disease but appear not to be
      essential for the ability of the host to control infection.

PMID- 21189221
TI  - Estrogen replacement therapy for the treatment of postmenopausal genitourinary
      tract dysfunction.
AB  - Considerable debate exists over the use of estrogen replacement therapy in post
      menopausal women. Valuable level 1 evidence has been obtained through randomized
      controlled clinical trials; even so, little consensus exists on its use. Several
      genitourinary complaints correlate temporally with estrogen depletion at the time
      of menopause; likewise, estrogen replacement has been felt to improve many of
      these conditions. We will review the indications and evidence for estrogen
      therapy in the treatment of genitourinary symptoms as well as the hallmark
      clinical trials that address urinary incontinence, overactive bladder symptoms,
      urinary tract infections, vaginal atrophy and dyspareunia.

PMID- 21189222
TI  - Epigenetics and transplantation: clinical applications of chromatin regulation.
AB  - Epigenetics is a field that has swiftly gained momentum over the past few years.
      It has been associated with applications in development, evolution and
      pathogenesis. In recent studies, however, a link has surfaced that connects
      epigenetic changes and transplantation. From its very beginning, transplantation
      medicine has been confronted with the looming specter of transplant rejection. It
      has been shown that epigenetic changes are at least partly involved in transplant
      outcomes; it is therefore of great importance to further investigate the exact
      mechanisms affecting transplantation outcome. The use of epigenetic markers for
      the determination of graft prognosis and the diagnosis of transplant rejection
      status promises to be an efficient and accurate means in clinical applications.
      As will be discussed in this review, enlisting the help of epigenetic mechanisms
      might not only facilitate the diagnosis of graft rejection, but also contribute
      to attenuation of transplant rejection. This would be a very desirable aid to the
      field of transplant medicine.

PMID- 21189220
TI  - Bromodomain coactivators in cancer, obesity, type 2 diabetes, and inflammation.
AB  - Double bromodomain proteins bind to acetylated lysines in histones, bringing
      associated histone modification and nucleosome remodeling activity to chromatin.
      The ability of bromodomain regulators to alter chromatin status and control gene
      expression has long been appreciated to be important in the development of
      certain human cancers. However, bromodomain proteins have now been found also to
      be critical, non-redundant players in diverse, non-malignant phenotypes,
      directing transcriptional programs that control adipogenesis, energy metabolism
      and inflammation. The fact that such different processes are functionally linked
      by the same molecular machinery suggests a common epigenetic basis to understand
      and interpret the origins of several important co-morbidities, such as asthma or
      cancer that occurs in obesity, and complex inflammatory diseases like
      cardiovascular disease, systemic lupus erythematosus, rheumatoid arthritis and
      insulin resistance that may be built on a common pro-inflammatory foundation.

PMID- 21189223
TI  - Angiogenesis inhibitors in prostate cancer therapy.
AB  - Limited treatment options exist for metastatic castrate-resistant prostate cancer
      (mCRPC). The concept of targeting tumors via anti-angiogenic mechanisms has been
      studied over the last decade, giving rise to a new class of anti-cancer drugs.
      Currently, the use of angiogenesis inhibition in prostate cancer is the focus of
      many ongoing clinical trials, with tumor progression and overall survival
      established as outcome measures. Several anti-angiogenic agents are currently
      under investigation with varying mechanisms by which they exert activity against
      prostate tumors. We describe the significant findings and outcomes of clinical
      trials involving the use of these drugs in mCRPC patients, along with how these
      results will translate to their use in the clinical setting. Open interventional
      trials that are currently recruiting participants are also mentioned. While the
      use of angiogenesis inhibition holds promise in the treatment of prostate cancer,
      several challenges still exist. The foreseeable clinical implications and
      limitations of anti-angiogenic therapy and the potential use of biomarkers are
      hereby discussed.

PMID- 21189225
TI  - Hormonal interactions between gut and brain.
AB  - No truly effective drugs exist to treat obesity, which is reaching pandemic
      proportions. The search for new treatments has led to an interest into the
      homeostatic system of central appetite regulation. Key components of this system
      include the hypothalamus and brainstem, the gut, and adipose tissue. It is now
      recognized that food intake leads to the release of various gut hormones. There
      are several anorectic (appetite suppressing) gut hormones released, including
      cholecystokinin, glucagon like peptide-1, oxyntomodulin, peptide tyrosine
      tyrosine, and pancreatic polypeptide. To date, only one example is known of an
      orexigenic (appetite stimulating) hormone, ghrelin. These hormones circulate in
      the blood and signal via vagal nerve afferents to communicate with the
      hypothalamus and brainstem. This information is integrated and processed in key
      hypothalamic nuclei. The arcuate nucleus appears to be a central controller of
      the appetite circuit, integrating both peripheral and central signals. This
      information is translated into downstream signals affecting body metabolism and
      food intake. Increased understanding and successful manipulation of this system
      should enable the design of a successful and much needed anti-obesity treatment.

PMID- 21189224
TI  - Systems approaches to molecular cancer diagnostics.
AB  - The search for improved molecular cancer diagnostics is a challenge for which
      systems approaches show great promise. As is becoming increasingly clear, cancer
      is a perpetually-evolving, highly multi-factorial disease. With next generation
      sequencing providing an ever-increasing amount of high-throughput data, the need
      for analytical tools that can provide meaningful context is critical. Systems
      approaches have demonstrated an ability to separate meaningful signal from noise
      that arises from population heterogeneity, heterogeneity within and across
      tumors, and multiple sources of technical variation when sufficient sample sizes
      are obtained and standardized measurement technologies are used. The ability to
      develop clinically useful molecular cancer diagnostics will be predicated on
      advancements on two major fronts: 1) more comprehensive and accurate measurements
      of multiple endpoints, and 2) more sophisticated analytical tools that synthesize
      high-throughput data into meaningful reflections of cellular states. To this end,
      systems approaches that have integrated transcriptomic data onto biomolecular
      networks have shown promise in their ability to classify tumor subtypes, predict
      clinical progression, and inform treatment options. Ultimately, the success of
      systems approaches will be measured by their ability to develop molecular cancer
      diagnostics through distilling complex, systems-wide information into actionable
      information in the clinic.

PMID- 21189226
TI  - Musical and linguistic expertise influence pre-attentive and attentive processing
      of non-speech sounds.
AB  - The aim of this experiment was two-fold. Our first goal was to determine whether
      linguistic expertise influences the pre-attentive [as reflected by the Mismatch
      Negativity - (MMN)] and the attentive processing (as reflected by behavioural
      discrimination accuracy) of non-speech, harmonic sounds. The second was to
      directly compare the effects of linguistic and musical expertise. To this end, we
      compared non-musician native speakers of a quantity language, Finnish, in which
      duration is a phonemically contrastive cue, with French musicians and French non
      musicians. Results revealed that pre-attentive and attentive processing of
      duration deviants was enhanced in Finn non-musicians and French musicians
      compared to French non-musicians. By contrast, MMN in French musicians was larger
      than in both Finns and French non-musicians for frequency deviants, whereas no
      between-group differences were found for intensity deviants. By showing similar
      effects of linguistic and musical expertise, these results argue in favor of
      common processing of duration in music and speech.

PMID- 21189227
TI  - Resveratrol down-regulates interferon-gamma-inducible inflammatory genes in
      macrophages: molecular mechanism via decreased STAT-1 activation.
AB  - Resveratrol (trans-3,4',5-trihydroxystilbene) is one of nonflavonoid polyphenolic
      phytoalexins found in various plant species, a number of which are components of
      human diet including grapes and red wines. Resveratrol has exerted several
      beneficial effects with anti-inflammation, cardioprotection and cancer
      chemoprevention. However, its mechanisms of action are not completely understood.
      In this study, we investigated effects of resveratrol on inflammatory gene
      expression in interferon (IFN)-gamma alone-stimulated macrophages and proposed a
      molecular basis underlying the action. Resveratrol inhibited IFN-gamma-induced
      production of nitric oxide (NO), IFN-gamma-inducible protein-10 (IP-10), or the
      monokine induced by IFN-gamma (MIG) in RAW 264.7 macrophages and also that of NO
      in primary macrophages derived from bone marrows of C3H/HeJ (toll-like receptor
      4(-/-)) mice. Moreover, resveratrol diminished IFN-gamma-induced protein levels
      of inducible NO synthase (iNOS), attenuated mRNA levels of iNOS, IP-10 or MIG as
      well as inhibited IFN-gamma-induced promoter activity of iNOS gene, indicating
      that the phytoalexin could down-regulate inflammatory genes at the transcription
      level. To understand a mechanism of the action, we tested resveratrol could
      affect the signal transducers and activation of transcription-1 (STAT-1), a
      pivotal transcription factor in IFN-gamma-induced expression of inflammatory
      genes. Resveratrol inhibited IFN-gamma-induced transcriptional activity of STAT-1
      in macrophages and also IFN-gamma-induced Tyr(701) or Ser(727) phosphorylation of
      STAT-1. We then focused on protein kinases upstream STAT-1 phosphorylation.
      Resveratrol inhibited IFN-gamma-induced activation of Janus kinase-2 (JAK-2) and
      also the extracellular signal-regulated kinase, in which JAK-2 was more
      sensitive. Taken together, this study proposes a new mechanism of resveratrol,
      blocking JAK/STAT-1 pathway that controls inflammatory responses in IFN-gamma
      activated macrophages.

PMID- 21189228
TI  - Curcumin inhibits adipocyte differentiation through modulation of mitotic clonal
      expansion.
AB  - Adipocyte differentiation is a key process in determining the number of mature
      adipocytes in the development of obesity. Here, we examined the function of
      curcumin, a dietary polyphenol found in turmeric, and its underlying mechanisms
      in adipocyte differentiation. Our study reveals that curcumin exerts an anti
      adipogenic function both in 3T3-L1 murine cells and in human primary
      preadipocytes as determined by intracellular lipid accumulation assay,
      quantitative analysis of adipocyte marker gene expression and a noninvasive
      multimodal Coherent Anti-Stokes Raman Scattering (CARS) microscopic analysis of
      intracellular curcumin. The inhibitory action of curcumin was largely limited to
      the early stage of adipocyte differentiation, where curcumin was found to inhibit
      mitotic clonal expansion (MCE) process as evidenced by impaired proliferation,
      cell-cycle entry into S phase and the S to G2/M phase transition of confluent
      cells, and levels of cell cycle-regulating proteins with no significant effect on
      cell viability and cytotoxicity. This, in turn, resulted in inhibition of mRNA
      levels of early adipogenic transcription factors, particularly Kruppel-like
      factor 5 (KLF5), CCAAT/enhancer binding proteinalpha (C/EBPalpha) and peroxisome
      proliferator-activated receptorgamma (PPARgamma), in the early stage of adipocyte
      differentiation. Supplementation with rosiglitazone, a PPARgamma ligand, during
      the early stage of adipocyte differentiation partially rescued curcumin-inhibited
      adipocyte differentiation. Collectively, our results show that curcumin is an
      anti-adipogenic dietary bioactive component largely involved in the modulation of
      the MCE process during the early stage of adipocyte differentiation.

PMID- 21189229
TI  - Activation of suicidal ideation with adjunctive rufinamide in bipolar disorder.
AB  - Antiepileptic drugs are effective psychotropics, especially for bipolar disorder,
      which leads to their use off-label in treatment-refractory cases. A recent
      publication suggests that rufinamide may be beneficial adjunctively for bipolar
      disorder with comorbid psychopathology. This report addresses two negative cases
      with significant psychiatric adverse effects: increased depression, agitation,
      and activation of suicidal ideation. These findings suggest that adjunctive
      rufinamide may lead to increased suicidal ideation in patients with treatment
      refractory bipolar disorder. Secondary to the course of severe bipolar disorder,
      rufinamide cannot be specifically implicated; however, clinicians should be aware
      of this potential significant adverse effect and monitor high-risk patients.
      Further studies are required to address rufinamide treatment efficacy and
      severity of adverse effects in patients with bipolar disorder.

PMID- 21189230
TI  - Theoretical considerations of tissue electroporation with high-frequency bipolar
      pulses.
AB  - This study introduces the use of high-frequency pulsed electric fields for tissue
      electroporation. Through the development of finite element models and the use of
      analytical techniques, electroporation with rectangular, bipolar pulses is
      investigated. The electric field and temperature distribution along with the
      associated transmembrane potential development are considered in a heterogeneous
      skin fold geometry. Results indicate that switching polarity on the nanosecond
      scale near the charging time of plasma membranes can greatly improve treatment
      outcomes in heterogeneous tissues. Specifically, high-frequency fields ranging
      from 500 kHz to 1 MHz are best suited to penetrate epithelial layers without
      inducing significant Joule heating, and cause electroporation in underlying
      cells.

PMID- 21189231
TI  - Interconnection of multichannel polyimide electrodes using anisotropic conductive
      films (ACFs) for biomedical applications.
AB  - In this paper, we propose a method for interconnecting soft polyimide (PI)
      electrodes using anisotropic conductive films (ACFs). Reliable and automated
      bonding was achieved through development of a desktop thermocompressive bonding
      device that could simultaneously deliver appropriate temperatures and pressures
      to the interconnection area. The bonding conditions were optimized by changing
      the bonding temperature and bonding pressure. The electrical properties were
      characterized by measuring the contact resistance of the ACF bonding area,
      yielding a measure that was used to optimize the applied pressure and
      temperature. The optimal conditions consisted of applying a pressure of 4 kg
      f/cm(2) and a temperature of 180  degrees C for 20 s. Although ACF base bonding
      is widely used in industry (e.g., liquid crystal display manufacturing), this
      study constitutes the first trial of a biomedical application. We performed a
      preliminary in vivo biocompatibility investigation of ACF bonded area. Using the
      optimized temperature and pressure conditions, we interconnected a 40-channel PI
      multielectrode device for measuring electroencephalography (EEG) signals from the
      skulls of mice. The electrical properties of electrode were characterized by
      measuring the impedance. Finally, EEG signals were measured from the mice skulls
      using the fabricated devices to investigate suitability for application to
      biomedical devices.

PMID- 21189232
TI  - Breaking the fixed-arrival-time restriction in reaching movements of neural
      prosthetic devices.
AB  - We routinely generate reaching arm movements to function independently. For
      paralyzed users of upper extremity neural prosthetic devices, flexible, high
      performance reaching algorithms will be critical to restoring quality-of-life.
      Previously, algorithms called real-time reach state equations (RSE) were
      developed to integrate the user's plan and execution-related neural activity to
      drive reaching movements to arbitrary targets. Preliminary validation under
      restricted conditions suggested that RSE might yield dramatic performance
      improvements. Unfortunately, real-world applications of RSE have been impeded
      because the RSE assumes a fixed, known arrival time. Recent animal-based
      prototypes attempted to break the fixed-arrival-time assumption by proposing a
      standard model (SM) that instead restricted the user's movements to a fixed,
      known set of targets. Here, we leverage general purpose filter design (GPFD) to
      break both of these critical restrictions, freeing the paralyzed user to make
      reaching movements to arbitrary target sets with various arrival times and
      definitive stopping. In silico validation predicts that the new approach, GPFD
      RSE, outperforms the SM while offering greater flexibility. We demonstrate the
      GPFD-RSE against SM in the simulated control of an overactuated 3-D virtual
      robotic arm with a real-time inverse kinematics engine.

PMID- 21189233
TI  - Three-dimensional imaging of ventricular activation and electrograms from
      intracavitary recordings.
AB  - Three-dimensional (3-D) mapping of the ventricular activation is of importance to
      better understand the mechanisms and facilitate management of ventricular
      arrhythmias. The goal of this study was to develop and evaluate a 3-D cardiac
      electrical imaging (3DCEI) approach for imaging myocardial electrical activation
      from the intracavitary electrograms (EGs) and heart-torso geometry information
      over the 3-D volume of the heart. The 3DCEI was evaluated in a swine model
      undergoing intracavitary noncontact mapping (NCM). Each animal's preoperative MRI
      data were acquired to construct the heart-torso model. NCM was performed with the
      Ensite 3000 system during acute ventricular pacing. Subsequent 3DCEI analyses
      were performed on the measured intracavitary EGs. The estimated initial sites
      (ISs) were compared to the precise pacing locations, and the estimated activation
      sequences (ASs) and EGs were compared to those recorded by the NCM system over
      the endocardial surface. In total, six ventricular sites from two pigs were
      paced. The averaged localization error of IS was 6.7 +/- 2.6 mm. The endocardial
      ASs and EGs as a subset of the estimated 3-D solutions were consistent with those
      reconstructed from the NCM system. The present results demonstrate that the
      intracavitary-recording-based 3DCEI approach can well localize the sites of
      initiation and can obtain physiologically reasonable ASs as well as EGs in an in
      vivo setting under control/paced conditions. This study suggests the feasibility
      of tomographic imaging of 3-D ventricular activation and 3-D EGs from
      intracavitary recordings.

PMID- 21189234
TI  - Learning associative memories by error backpropagation.
AB  - In this paper, a method for the design of Hopfield networks, bidirectional and
      multidirectional associative memories with asymmetric connections, is proposed.
      The given patterns can be assigned as locally asymptotically stable equilibria of
      the network by training a single-layer feedforward network. It is shown that the
      robustness in respect to acceptable noise in the input of the constructed
      networks is enhanced as the memory dimension increases and weakened as the number
      of the stored patterns grows. More important is that the remembered patterns are
      not necessarily of binary forms. Neural associative memories for storing gray
      level images are constructed based on the proposed method. Numerical simulations
      show that the proposed method is efficient for the design of Hopfield-type
      recurrent neural networks.

PMID- 21189235
TI  - Lower upper bound estimation method for construction of neural network-based
      prediction intervals.
AB  - Prediction intervals (PIs) have been proposed in the literature to provide more
      information by quantifying the level of uncertainty associated to the point
      forecasts. Traditional methods for construction of neural network (NN) based PIs
      suffer from restrictive assumptions about data distribution and massive
      computational loads. In this paper, we propose a new, fast, yet reliable method
      for the construction of PIs for NN predictions. The proposed lower upper bound
      estimation (LUBE) method constructs an NN with two outputs for estimating the
      prediction interval bounds. NN training is achieved through the minimization of a
      proposed PI-based objective function, which covers both interval width and
      coverage probability. The method does not require any information about the upper
      and lower bounds of PIs for training the NN. The simulated annealing method is
      applied for minimization of the cost function and adjustment of NN parameters.
      The demonstrated results for 10 benchmark regression case studies clearly show
      the LUBE method to be capable of generating high-quality PIs in a short time.
      Also, the quantitative comparison with three traditional techniques for
      prediction interval construction reveals that the LUBE method is simpler, faster,
      and more reliable.

PMID- 21189236
TI  - Learning ensembles of neural networks by means of a Bayesian artificial immune
      system.
AB  - In this paper, we apply an immune-inspired approach to design ensembles of
      heterogeneous neural networks for classification problems. Our proposal, called
      Bayesian artificial immune system, is an estimation of distribution algorithm
      that replaces the traditional mutation and cloning operators with a probabilistic
      model, more specifically a Bayesian network, representing the joint distribution
      of promising solutions. Among the additional attributes provided by the Bayesian
      framework inserted into an immune-inspired search algorithm are the automatic
      control of the population size along the search and the inherent ability to
      promote and preserve diversity among the candidate solutions. Both are attributes
      generally absent from alternative estimation of distribution algorithms, and both
      were shown to be useful attributes when implementing the generation and selection
      of components of the ensemble, thus leading to high-performance classifiers.
      Several aspects of the design are illustrated in practical applications,
      including a comparative analysis with other attempts to synthesize ensembles.

PMID- 21189237
TI  - Objective functions of online weight noise injection training algorithms for
      MLPs.
AB  - Injecting weight noise during training has been a simple strategy to improve the
      fault tolerance of multilayer perceptrons (MLPs) for almost two decades, and
      several online training algorithms have been proposed in this regard. However,
      there are some misconceptions about the objective functions being minimized by
      these algorithms. Some existing results misinterpret that the prediction error of
      a trained MLP affected by weight noise is equivalent to the objective function of
      a weight noise injection algorithm. In this brief, we would like to clarify these
      misconceptions. Two weight noise injection scenarios will be considered: one is
      based on additive weight noise injection and the other is based on multiplicative
      weight noise injection. To avoid the misconceptions, we use their mean updating
      equations to analyze the objective functions. For injecting additive weight noise
      during training, we show that the true objective function is identical to the
      prediction error of a faulty MLP whose weights are affected by additive weight
      noise. It consists of the conventional mean square error and a smoothing
      regularizer. For injecting multiplicative weight noise during training, we show
      that the objective function is different from the prediction error of a faulty
      MLP whose weights are affected by multiplicative weight noise. With our results,
      some existing misconceptions regarding MLP training with weight noise injection
      can now be resolved.

PMID- 21189238
TI  - Multiple player tracking in sports video: a dual-mode two-way bayesian inference
      approach with progressive observation modeling.
AB  - Multiple object tracking (MOT) is a very challenging task yet of fundamental
      importance for many practical applications. In this paper, we focus on the
      problem of tracking multiple players in sports video which is even more difficult
      due to the abrupt movements of players and their complex interactions. To handle
      the difficulties in this problem, we present a new MOT algorithm which
      contributes both in the observation modeling level and in the tracking strategy
      level. For the observation modeling, we develop a progressive observation
      modeling process that is able to provide strong tracking observations and greatly
      facilitate the tracking task. For the tracking strategy, we propose a dual-mode
      two-way Bayesian inference approach which dynamically switches between an offline
      general model and an online dedicated model to deal with single isolated object
      tracking and multiple occluded object tracking integrally by forward filtering
      and backward smoothing. Extensive experiments on different kinds of sports
      videos, including football, basketball, as well as hockey, demonstrate the
      effectiveness and efficiency of the proposed method.

PMID- 21189239
TI  - Optimal image alignment with random projections of manifolds: algorithm and
      geometric analysis.
AB  - This paper addresses the problem of image alignment based on random measurements.
      Image alignment consists of estimating the relative transformation between a
      query image and a reference image. We consider the specific problem where the
      query image is provided in compressed form in terms of linear measurements
      captured by a vision sensor. We cast the alignment problem as a manifold distance
      minimization problem in the linear subspace defined by the measurements. The
      transformation manifold that represents synthesis of shift, rotation, and
      isotropic scaling of the reference image can be given in closed form when the
      reference pattern is sparsely represented over a parametric dictionary. We show
      that the objective function can then be decomposed as the difference of two
      convex functions (DC) in the particular case where the dictionary is built on
      Gaussian functions. Thus, the optimization problem becomes a DC program, which in
      turn can be solved globally by a cutting plane method. The quality of the
      solution is typically affected by the number of random measurements and the
      condition number of the manifold that describes the transformations of the
      reference image. We show that the curvature, which is closely related to the
      condition number, remains bounded in our image alignment problem, which means
      that the relative transformation between two images can be determined optimally
      in a reduced subspace.

PMID- 21189240
TI  - Elastic sequence correlation for human action analysis.
AB  - This paper addresses the problem of automatically analyzing and understanding
      human actions from video footage. An "action correlation" framework, elastic
      sequence correlation (ESC), is proposed to identify action subsequences from a
      database of (possibly long) video sequences that are similar to a given query
      video action clip. In particular, we show that two well-known algorithms, namely
      approximate pattern matching in computer and information sciences and dynamic
      time warping (DTW) method in signal processing, are special cases of our ESC
      framework. The proposed framework is applied to two important real-world
      applications: action pattern retrieval, as well as action segmentation and
      recognition, where, on average, its run time speed (in matlab) is about 3.3
      frames per second. In addition, comparing with the state-of-the-art algorithms on
      a number of challenging data sets, our approach is demonstrated to perform
      competitively.

PMID- 21189241
TI  - ViBe: a universal background subtraction algorithm for video sequences.
AB  - This paper presents a technique for motion detection that incorporates several
      innovative mechanisms. For example, our proposed technique stores, for each
      pixel, a set of values taken in the past at the same location or in the
      neighborhood. It then compares this set to the current pixel value in order to
      determine whether that pixel belongs to the background, and adapts the model by
      choosing randomly which values to substitute from the background model. This
      approach differs from those based upon the classical belief that the oldest
      values should be replaced first. Finally, when the pixel is found to be part of
      the background, its value is propagated into the background model of a
      neighboring pixel. We describe our method in full details (including pseudo-code
      and the parameter values used) and compare it to other background subtraction
      techniques. Efficiency figures show that our method outperforms recent and proven
      state-of-the-art methods in terms of both computation speed and detection rate.
      We also analyze the performance of a downscaled version of our algorithm to the
      absolute minimum of one comparison and one byte of memory per pixel. It appears
      that even such a simplified version of our algorithm performs better than
      mainstream techniques.

PMID- 21189242
TI  - Comparison of texture analysis schemes under nonideal conditions.
AB  - Several recent advancements in the field of texture analysis prompt some
      fundamental questions. For instance, what is the true impact of these novel
      advancements under real-world environments? When do these novel advancements fail
      to perform? Which methods perform better and under what conditions? In this work,
      we investigate these and other issues under nonideal image acquisition
      environments, specifically, environments with changing conditions due to
      illumination variations and those caused by both affine and nonaffine
      transformations. We study the performance of nine popular texture analysis
      algorithms using three different datasets, with varying levels of difficulty.
      Experiments are performed on nonideal texture datasets under five different
      setups. We find that most state-of-the-art techniques do not perform well under
      these conditions. To a large extent, their performance under nonideal conditions
      depends critically on the nature of the textural surface. Moreover, most
      techniques fail to perform reliably when the number of classes in the dataset is
      increased significantly, over the regular-size datasets used in previous work.
      Multiscale features performed reasonably well against variations caused by
      illumination and rotation but are prone to fail under changes in scale.
      Surprisingly, the performance for most of the algorithms is generally stable on
      structured or periodic textures, even with variations in illumination or affine
      transformations.

PMID- 21189243
TI  - Text segmentation for MRC document compression.
AB  - The mixed raster content (MRC) standard (ITU-T T.44) specifies a framework for
      document compression which can dramatically improve the compression/quality
      tradeoff as compared to traditional lossy image compression algorithms. The key
      to MRC compression is the separation of the document into foreground and
      background layers, represented as a binary mask. Therefore, the resulting quality
      and compression ratio of a MRC document encoder is highly dependent upon the
      segmentation algorithm used to compute the binary mask. In this paper, we propose
      a novel multiscale segmentation scheme for MRC document encoding based upon the
      sequential application of two algorithms. The first algorithm, cost optimized
      segmentation (COS), is a blockwise segmentation algorithm formulated in a global
      cost optimization framework. The second algorithm, connected component
      classification (CCC), refines the initial segmentation by classifying feature
      vectors of connected components using an Markov random field (MRF) model. The
      combined COS/CCC segmentation algorithms are then incorporated into a multiscale
      framework in order to improve the segmentation accuracy of text with varying
      size. In comparisons to state-of-the-art commercial MRC products and selected
      segmentation algorithms in the literature, we show that the new algorithm
      achieves greater accuracy of text detection but with a lower false detection rate
      of nontext features. We also demonstrate that the proposed segmentation algorithm
      can improve the quality of decoded documents while simultaneously lowering the
      bit rate.

PMID- 21189244
TI  - An approximation of interval type-2 fuzzy controllers using fuzzy ratio switching
      type-1 fuzzy controllers.
AB  - In this paper, the interval type-2 fuzzy controllers (FC(IT2)s) are approximated
      using the fuzzy ratio switching type-1 FCs to avoid the complex type-reduction
      process required for the interval type-2 FCs. The fuzzy ratio switching type-1
      FCs (FC(FRST1)s) are designed to be a fuzzy combination of the possible-leftmost
      and possible-rightmost type-1 FCs. The fuzzy ratio switching type-1 fuzzy control
      technique is applied with the sliding control technique to realize the hybrid
      fuzzy ratio switching type-1 fuzzy sliding controllers (HFSC(FRST1)s) for the
      double-pendulum-and-cart system. The simulation results and comparisons with
      other approaches are provided to demonstrate the effectiveness of the proposed
      HFSC(FRST1)s.

PMID- 21189245
TI  - Reverse total shoulder arthroplasty: current concepts, results, and component
      wear analysis.

PMID- 21189246
TI  - The evolution of elbow arthroplasty: innovative solutions to complex clinical
      problems.

PMID- 21189247
TI  - Magnetic resonance imaging of the musculoskeletal system: basic science, pulse
      sequences, and a systematic approach to image interpretation.

PMID- 21189248
TI  - Oncogenic activity of Ect2 is regulated through protein kinase C iota-mediated
      phosphorylation.
AB  - The Rho GTPase guanine nucleotide exchange factor Ect2 is genetically and
      biochemically linked to the PKCiota oncogene in non-small cell lung cancer
      (NSCLC). Ect2 is overexpressed and mislocalized to the cytoplasm of NSCLC cells
      where it binds the oncogenic PKCiota-Par6 complex, leading to activation of the
      Rac1 small GTPase. Here, we identify a previously uncharacterized phosphorylation
      site on Ect2, threonine 328, that serves to regulate the oncogenic activity of
      Ect2 in NSCLC cells. PKCiota directly phosphorylates Ect2 at Thr-328 in vitro,
      and RNAi-mediated knockdown of either PKCiota or Par6 leads to a decrease in
      phospho-Thr-328 Ect2, indicating that PKCiota regulates Thr-328 Ect2
      phosphorylation in NSCLC cells. Both wild-type Ect2 and a phosphomimetic T328D
      Ect2 mutant bind the PKCiota-Par6 complex, activate Rac1, and restore transformed
      growth and invasion when expressed in NSCLC cells made deficient in endogenous
      Ect2 by RNAi-mediated knockdown. In contrast, a phosphorylation-deficient T328A
      Ect2 mutant fails to bind the PKCiota-Par6 complex, activate Rac1, or restore
      transformation. Our data support a model in which PKCiota-mediated
      phosphorylation regulates Ect2 binding to the oncogenic PKCiota-Par6 complex
      thereby activating Rac1 activity and driving transformed growth and invasion.

PMID- 21189249
TI  - T cell receptor (TCR)-induced tyrosine phosphorylation dynamics identifies THEMIS
      as a new TCR signalosome component.
AB  - Stimulation of the T cell antigen receptor (TCR) induces formation of a
      phosphorylation-dependent signaling network via multiprotein complexes, whose
      compositions and dynamics are incompletely understood. Using stable isotope
      labeling by amino acids in cell culture (SILAC)-based quantitative proteomics, we
      investigated the kinetics of signal propagation after TCR-induced protein
      tyrosine phosphorylation. We confidently assigned 77 proteins (of 758 identified)
      as a direct or indirect consequence of tyrosine phosphorylation that proceeds in
      successive "signaling waves" revealing the temporal pace at which tyrosine
      kinases activate cellular functions. The first wave includes thymocyte-expressed
      molecule involved in selection (THEMIS), a protein recently implicated in
      thymocyte development but whose signaling role is unclear. We found that tyrosine
      phosphorylation of THEMIS depends on the presence of the scaffold proteins Linker
      for activation of T cells (LAT) and SH2 domain-containing lymphocyte protein of
      76 kDa (SLP-76). THEMIS associates with LAT, presumably via the adapter growth
      factor receptor-bound protein 2 (Grb2) and with phospholipase Cgamma1 (PLC
      gamma1). RNAi-mediated THEMIS knock-down inhibited TCR-induced IL-2 gene
      expression due to reduced ERK and nuclear factor of activated T cells
      (NFAT)/activator protein 1 (AP-1) signaling, whereas JNK, p38, or nuclear factor
      kappaB (NF-kappaB) activation were unaffected. Our study reveals the dynamics of
      TCR-dependent signaling networks and suggests a specific role for THEMIS in early
      TCR signalosome function.

PMID- 21189250
TI  - Phosphorylation-dependent C-terminal binding of 14-3-3 proteins promotes cell
      surface expression of HIV co-receptor GPR15.
AB  - Membrane trafficking is dictated by dynamic molecular interactions involving
      discrete determinants in the cargo proteins and the intracellular transport
      machineries. We have previously reported that cell surface expression of GPR15, a
      G protein-coupled receptor (GPCR) that serves as a co-receptor for HIV, is
      correlated with the mode III binding of 14-3-3 proteins to the receptor C
      terminus. Here we provide a mechanistic basis for the role of 14-3-3 in promoting
      the cell surface expression of GPR15. The Ala mutation of penultimate phospho-Ser
      (S359A) that abolishes 14-3-3 binding resulted in substantially reduced O
      glycosylation and the cell surface expression of GPR15. The surface membrane
      protein CD8 fused with the C-terminal tail of GPR15(S359A) mutant was re
      localized in the endoplasmic reticulum (ER). In the context of S359A mutation,
      the additional mutations in the upstream stretch of basic residues (RXR motif)
      restored O-glycosylation and the cell surface expression. The RXR motif was
      responsible for the interaction with coatomer protein I (COPI), which was
      inversely correlated with the 14-3-3 binding and cell surface expression. These
      results suggest that 14-3-3 binding promotes cell surface expression of GPR15 by
      releasing the receptor from ER retrieval/retention pathway that is mediated by
      the interaction of RXR motif and COPI. Moreover, 14-3-3 binding substantially
      increased the stability of GPR15 protein. Thus 14-3-3 proteins play multiple
      roles in biogenesis and trafficking of an HIV co-receptor GPR15 to control its
      cell surface density in response to the phosphorylation signal.

PMID- 21189251
TI  - Co-precipitation of phosphate and iron limits mitochondrial phosphate
      availability in Saccharomyces cerevisiae lacking the yeast frataxin homologue
      (YFH1).
AB  - Saccharomyces cerevisiae cells lacking the yeast frataxin homologue (Deltayfh1)
      accumulate iron in the mitochondria in the form of nanoparticles of ferric
      phosphate. The phosphate content of Deltayfh1 mitochondria was higher than that
      of wild-type mitochondria, but the proportion of mitochondrial phosphate that was
      soluble was much lower in Deltayfh1 cells. The rates of phosphate and iron uptake
      in vitro by isolated mitochondria were higher for Deltayfh1 than wild-type
      mitochondria, and a significant proportion of the phosphate and iron rapidly
      became insoluble in the mitochondrial matrix, suggesting co-precipitation of
      these species after oxidation of iron by oxygen. Increasing the amount of
      phosphate in the medium decreased the amount of iron accumulated by Deltayfh1
      cells and improved their growth in an iron-dependent manner, and this effect was
      mostly transcriptional. Overexpressing the major mitochondrial phosphate carrier,
      MIR1, slightly increased the concentration of soluble mitochondrial phosphate and
      significantly improved various mitochondrial functions (cytochromes, [Fe-S]
      clusters, and respiration) in Deltayfh1 cells. We conclude that in Deltayfh1
      cells, soluble phosphate is limiting, due to its co-precipitation with iron.

PMID- 21189252
TI  - Sulfurtransferases 1 and 2 play essential roles in embryo and seed development in
      Arabidopsis thaliana.
AB  - Sulfurtransferases (STRs) catalyze the transfer of a sulfur atom from a donor to
      a suitable acceptor molecule. The Arabidopsis thaliana genome encodes 20 putative
      STR proteins. The biological functions of most are unclear. We found that STR1
      and STR2 play important roles in embryo/seed development. Mutation of STR1 alone
      resulted in a shrunken seed phenotype, although growth and development of
      vegetative and reproductive organs were not affected. The shrunken seed phenotype
      was associated with the delayed/arrested embryo development, in most cases, at
      the heart stage. The embryo defect of str1 mutant is not fully penetrant.
      Approximately 12.5% of embryos developed further and formed normal looking seeds.
      In severely shrunken seeds, no embryo could be identified after seed collection.
      Partially shrunken seeds that contained viable embryos could still germinate.
      However, cotyledons of the seedlings from such seeds were abnormal. An STR1-GUS
      fusion reporter revealed that the STR1 gene was universally expressed, with high
      levels of expression in specific tissues/organs including embryos. The incomplete
      penetrance of str1 embryo/seed phenotype is a result of functional STR2. Single
      str2 mutant had no phenotype. However, no str1(-/-)/str2(-/-) double mutant
      embryos were able to develop past the heart stage. Furthermore, STR2 is haplo
      insufficient in str1 mutant background, and str1(-/-)/str2(+/-) embryos were 100%
      lethal. These data provide new insights into the biological functions of the
      ubiquitous sulfurtransferase in Arabidopsis embryogenesis and seed development.

PMID- 21189253
TI  - The unique transcriptional activation domain of nuclear factor-I-X3 is critical
      to specifically induce marker gene expression in astrocytes.
AB  - Transcription factors of the nuclear factor 1 (NFI) family regulate normal brain
      development in vertebrates. However, multiple splice variants of four NFI
      isoforms exist, and their biological functions have yet to be elucidated. Here,
      we cloned and analyzed human NFI-X3, a novel splice variant of the nfix gene,
      which contains a unique transcriptional activation (TA) domain completely
      conserved in primates. In contrast to previously cloned NFI-X1, overexpression of
      NFI-X3 potently activates NFI reporters, including glial fibrillary acidic
      protein (GFAP) reporter, in astrocytes and glioma cells. The GAL4 fusion protein
      containing the TA domain of NFI-X3 strongly activates the GAL4 reporter, whereas
      the TA domain of NFI-X1 is ineffective. The expression of NFI-X3 is dramatically
      up-regulated during the differentiation of neural progenitors to astrocytes and
      precedes the expression of astrocyte markers, such as GFAP and SPARCL1 (Secreted
      Protein, Acidic and Rich in Cysteines-like 1). Overexpression of NFI-X3
      dramatically up-regulates GFAP and SPARCL1 expression in glioma cells, whereas
      the knockdown of NFI-X3 diminishes the expression of both GFAP and SPARCL1 in
      astrocytes. Although activation of astrocyte-specific genes involves DNA
      demethylation and subsequent increase of histone acetylation, NFI-X3 activates
      GFAP expression, in part, by inducing alterations in the nucleosome architecture
      that lead to the increased recruitment of RNA polymerase II.

PMID- 21189254
TI  - Redesign of a plugged beta-barrel membrane protein.
AB  - The redesign of biological nanopores is focused on bacterial outer membrane
      proteins and pore-forming toxins, because their robust beta-barrel structure
      makes them the best choice for developing stochastic biosensing elements. Using
      membrane protein engineering and single-channel electrical recordings, we
      explored the ferric hydroxamate uptake component A (FhuA), a monomeric 22
      stranded beta-barrel protein from the outer membrane of Escherichia coli. FhuA
      has a luminal cross-section of 3.1 * 4.4 nm and is filled by a globular N
      terminal cork domain. Various redesigned FhuA proteins were investigated,
      including single, double, and multiple deletions of the large extracellular loops
      and the cork domain. We identified four large extracellular loops that partially
      occlude the lumen when the cork domain is removed. The newly engineered protein,
      FhuADeltaC/Delta4L, was the result of a removal of almost one-third of the total
      number of amino acids of the wild-type FhuA (WT-FhuA) protein. This extensive
      protein engineering encompassed the entire cork domain and four extracellular
      loops. Remarkably, FhuADeltaC/Delta4L forms a functional open pore in planar
      lipid bilayers, with a measured unitary conductance of ~4.8 nanosiemens, which is
      much greater than the values recorded previously with other engineered FhuA
      protein channels. There are numerous advantages and prospects of using such an
      engineered outer membrane protein not only in fundamental studies of membrane
      protein folding and design, and the mechanisms of ion conductance and gating, but
      also in more applicative areas of stochastic single-molecule sensing of proteins
      and nucleic acids.

PMID- 21189255
TI  - Dual functions of T-box 3 (Tbx3) in the control of self-renewal and
      extraembryonic endoderm differentiation in mouse embryonic stem cells.
AB  - Embryonic stem cells (ESCs) possess the capacity to proliferate indefinitely in
      an undifferentiated state and to differentiate into various cell types in an
      organism. However, the critical question of how self-renewal and differentiation
      are precisely regulated in ESCs is not entirely understood at present. Here, we
      report the essential role of Tbx3, a pluripotency-related transcription factor of
      the T-box gene family, for both the maintenance of self-renewal of mouse ESCs and
      for their differentiation into extraembryonic endoderm (ExEn). We show that Tbx3
      is highly expressed in ExEn cells in addition to undifferentiated ESCs. Knockdown
      of Tbx3 expression using tetracycline-regulated Tbx3 siRNA resulted in the
      attenuation of ESC self-renewal ability and aberrant differentiation processes,
      including reduced ExEn differentiation but enhanced ectoderm and trophectoderm
      differentiation. Conversely, inducible forced expression of Tbx3 triggered ExEn
      lineage commitment. Mechanistically, Tbx3 directly activated the expression of
      Gata6, an essential regulator of ExEn. Interestingly, Tbx3 modulated H3K27me3
      modification and the association of the PRC2 complex with the promoter region of
      Gata6. Taken together, the results of this study revealed a previously
      unappreciated role of a pluripotency factor in ExEn differentiation.
      Additionally, our data reveal that Tbx3 may function through direct binding and
      epigenetic modification of histones on the Gata6 promoter to maintain the ExEn
      differentiation potential of ESCs.

PMID- 21189256
TI  - Amphipathic tail-anchoring peptide and Bcl-2 homology domain-3 (BH3) peptides
      from Bcl-2 family proteins induce apoptosis through different mechanisms.
AB  - Bcl-2 homology domain-3 (BH3) peptides are potent cancer therapeutic reagents
      that target regulators of apoptotic cell death in cancer cells. However, their
      cytotoxic effects are affected by different expression levels of Bcl-2 family
      proteins. We recently found that the amphipathic tail-anchoring peptide (ATAP)
      from Bfl-1, a bifunctional Bcl-2 family member, produced strong pro-apoptotic
      activity by permeabilizing the mitochondrial outer membrane. Here, we test
      whether the activity of ATAP requires other cellular factors and whether ATAP has
      an advantage over the BH3 peptides in targeting cancer cells. Confocal
      microscopic imaging illustrates specific targeting of ATAP to mitochondria,
      whereas BH3 peptides show diffuse patterns of cytosolic distribution. Although
      the pro-apoptotic activities of BH3 peptides are largely inhibited by either
      overexpression of anti-apoptotic Bcl-2 or Bcl-xL or nullification of pro
      apoptotic Bax and Bak in cells, the pro-apoptotic function of ATAP is not
      affected by these cellular factors. Reconstitution of synthetic ATAP into
      liposomal membranes results in release of fluorescent molecules of the size of
      cytochrome c from the liposomes, suggesting that the membrane permeabilizing
      activity of ATAP does not require additional protein factors. Because ATAP can
      target to the mitochondrial membrane and its pro-apoptotic activity does not
      depend on the content of Bcl-2 family proteins, it represents a promising
      candidate for anti-cancer drugs that can potentially overcome the intrinsic
      apoptosis-resistant nature of cancer cells.

PMID- 21189257
TI  - PP1 cooperates with ASPP2 to dephosphorylate and activate TAZ.
AB  - The Hippo pathway regulates organ size by controlling both cell proliferation and
      apoptosis. TAZ functions as a transcriptional co-activator downstream of the
      Hippo pathway and has been implicated in human cancer development. A key step in
      the Hippo-TAZ pathway is phosphorylation of TAZ by LATS kinase, which leads to
      TAZ inhibition by both cytoplasmic retention and degradation. However, the
      mechanism of TAZ dephosphorylation and the responsible phosphatase are unknown.
      Here, we identified PP1 as a bona fide TAZ phosphatase. PP1A dephosphorylates TAZ
      at Ser-89 and Ser-311, promotes TAZ nuclear translocation, and stabilizes TAZ by
      disrupting the binding to the SCF E3 ubiquitin ligase. Furthermore, ASPP2
      facilitates the interaction between TAZ and PP1 to promote TAZ dephosphorylation.
      As a result, PP1 and ASPP2 increase TAZ-dependent gene expression. This study
      demonstrates that PP1A and ASPP2 play a critical role in promoting TAZ function
      by antagonizing the LATS kinase through TAZ dephosphorylation.

PMID- 21189258
TI  - Inhibition of proinflammatory RANTES expression by TGF-beta1 is mediated by
      glycogen synthase kinase-3beta-dependent beta-catenin signaling.
AB  - TGF-beta1 is a pleiotropic cytokine with potent anti-inflammation property.
      However, the mechanisms underlying TGF-beta1 suppression of inflammation remain
      largely unexplored. In this study, we demonstrated that TGF-beta1 inhibited TNF
      alpha- or IL-1-induced RANTES expression in human kidney tubular epithelial cells
      (HKC-8). To delineate the mechanism by which TGF-beta1 inhibits RANTES
      expression, we examined the potential signal pathway activated by TGF-beta1 in
      suppressing NF-kappaB signaling. TGF-beta1 affected neither TNF-alpha-induced
      IkappaBalpha phosphorylation and subsequent degradation, nor p65 NF-kappaB
      phosphorylation and its nuclear translocation. However, TGF-beta1 could inhibit
      p65 and p50 binding to the kappaB site in human RANTES promoter as revealed by
      chromatin immunoprecipitation assay and protein-DNA binding assay. We found that
      TGF-beta1 induced glycogen synthase kinase-3beta (GSK-3beta) phosphorylation on
      Ser-9 in HKC-8 cells, leading to its inactivation. Knockdown of GSK-3beta
      mimicked TGF-beta1 and inhibited RANTES induction, whereas overexpression of GSK
      3beta abolished the inhibitory effect of TGF-beta1 and completely restored RANTES
      expression. Furthermore, TGF-beta1 induced the dephosphorylation and activation
      of beta-catenin, a major downstream target of GSK-3beta. Ectopic expression of
      constitutively active beta-catenin mimicked the TGF-beta1 effect and completely
      suppressed RANTES expression induced by TNF-alpha. Interestingly, TGF-beta1
      induced a physical interaction between beta-catenin and p65 NF-kappaB, which
      prevented p65 binding to the kappaB site, sequestered its trans-activating
      activity, and repressed p65-mediated gene transcription. We conclude that TGF
      beta1 inhibition of proinflammatory RANTES expression is mediated by beta-catenin
      triggered blockade of NF-kappaB signaling.

PMID- 21189259
TI  - Comprehensive biochemical analysis of rare prostacyclin receptor variants: study
      of association of signaling with coronary artery obstruction.
AB  - Currently, pharmacogenetic studies are at an impasse as the low prevalence (<2%)
      of most variants hinder their pharmacogenetic analysis with population sizes
      often inadequate for sufficiently powered studies. Grouping rare mutations by
      functional phenotype rather than mutation site can potentially increase sample
      size. Using human population-based studies (n = 1,761) to search for
      dysfunctional human prostacyclin receptor (hIP) variants, we recently discovered
      18 non-synonymous mutations, all with frequencies less than 2% in our study
      cohort. Eight of the 18 had defects in binding, activation, and/or protein
      stability/folding. Mutations (M113T, L104R, and R279C) in three highly conserved
      positions demonstrated severe misfolding manifested by impaired binding and
      activation of cell surface receptors. To assess for association with coronary
      artery disease, we performed a case-control study comparing coronary angiographic
      results from patients with reduced cAMP production arising from the non
      synonymous mutations (n = 23) with patients with non-synonymous mutations that
      had no reduction in cAMP (n = 17). Major coronary artery obstruction was
      significantly increased in the dysfunctional mutation group in comparison with
      the silent mutations. We then compared the 23 dysfunctional receptor patients
      with 69 age- and risk factor-matched controls (1:3). This verified the
      significantly increased coronary disease in the non-synonymous dysfunctional
      variant cohort. This study demonstrates the potential utility of in vitro
      functional characterization in predicting clinical phenotypes and represents the
      most comprehensive characterization of human prostacyclin receptor genetic
      variants to date.

PMID- 21189260
TI  - TBK1-associated protein in endolysosomes (TAPE) is an innate immune regulator
      modulating the TLR3 and TLR4 signaling pathways.
AB  - The innate immune system elicits the first wave of immune responses against
      pathogen infection. Its operational modes are complex and have yet to be defined.
      Here, we report the identification of an innate immune regulator termed TAPE
      (TBK1-associated protein in endolysosomes), previously known as CC2D1A/Freud
      1/Aki-1, which modulates the TLR3 and TLR4 pathways. We found that TAPE activated
      the TBK1, NF-kappaB, and ERK pathways leading to IFN-beta and inflammatory
      cytokine induction. TAPE was shown to colocalize with endosomal marker Rab5 and
      lysosomal marker LAMP1 in mammalian cells, suggesting that TAPE resided in
      endolysosomes. Knockdown of TAPE selectively impaired the TLR3 and endocytic TLR4
      pathways to IFN-beta induction. Furthermore, TAPE interacted and synergized with
      Trif to activate IFN-beta. TAPE knockdown failed to block Trif-mediated IFN-beta
      induction, whereas Trif knockdown impaired the TLR3 and TAPE cooperation on IFN
      beta induction, suggesting that TAPE acts upstream of Trif. Together, our data
      demonstrate a central role for TAPE in linking TLR3 and TLR4 to innate immune
      defenses at an early step.

PMID- 21189261
TI  - Deficient tryptophan catabolism along the kynurenine pathway reveals that the
      epididymis is in a unique tolerogenic state.
AB  - Indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting enzyme of
      tryptophan catabolism through the kynurenine pathway. Intriguingly, IDO is
      constitutively and highly expressed in the mammalian epididymis in contrast to
      most other tissues where IDO is induced by proinflammatory cytokines, such as
      interferons. To gain insight into the role of IDO in the physiology of the
      mammalian epididymis, we studied both wild type and Ido1(-/-)-deficient mice. In
      the caput epididymis of Ido1(-/-) animals, the lack of IDO activity was not
      compensated by other tryptophan-catabolizing enzymes and led to the loss of
      kynurenine production. The absence of IDO generated an inflammatory state in the
      caput epididymis as revealed by an increased accumulation of various inflammation
      markers. The absence of IDO also increased the tryptophan content of the caput
      epididymis and generated a parallel increase in caput epididymal protein content
      as a consequence of deficient proteasomal activity. Surprisingly, the lack of IDO
      expression had no noticeable impact on overall male fertility but did induce
      highly significant increases in both the number and the percentage of abnormal
      spermatozoa. These changes coincided with a significant decrease in white blood
      cell count in epididymal fluid compared with wild type mice. These data provide
      support for IDO playing a hitherto unsuspected role in sperm quality control in
      the epididymis involving the ubiquitination of defective spermatozoa and their
      subsequent removal.

PMID- 21189262
TI  - Evidence of a role for activation of Wnt/beta-catenin signaling in the resistance
      of plasma cells to lenalidomide.
AB  - Lenalidomide plays an important role in our chemotherapeutic armamentarium
      against multiple myeloma, in part by exerting direct anti-proliferative and pro
      apoptotic effects. Unfortunately, long-term exposure leads to the development of
      drug resistance through unknown mechanisms, and we therefore sought to identify
      pathways that could be responsible for this phenotype. Chronic drug exposure
      produced myeloma cell lines that were tolerant of the direct effects of
      lenalidomide, with a degree of resistance of up to 2,500-fold. Gene expression
      profiling and pathway analysis identified dysregulation of the Wnt/beta-catenin
      pathway as a consistent change across four independent cell isolates, and a pair
      of primary plasma cell samples. Acute drug treatment also increased beta-catenin
      transcription by 3-fold or more, and both acute and chronic exposure resulted in
      enhanced accumulation of beta-catenin protein by up to 20-fold or more. This
      produced Wnt/beta-catenin pathway activation, as judged by increased activity of
      a lymphoid enhancer factor/T-cell factor promoter reporter, and enhanced
      accumulation of the downstream targets cyclin D1 and c-Myc. Components of the
      beta-catenin destruction complex were also impacted by lenalidomide, which
      suppressed casein kinase 1alpha expression while augmenting glycogen synthase
      kinase 3alpha/beta phosphorylation. Stimulation of Wnt/beta-catenin signaling
      with recombinant Wnt-3a, or by overexpression of beta-catenin, reduced the anti
      proliferative activity of lenalidomide. Conversely, suppression of beta-catenin
      with small hairpin RNAs restored plasma cell sensitivity to lenalidomide.
      Together, these findings support the hypothesis that lenalidomide mediates
      activation of Wnt/beta-catenin signaling in plasma cells as a mechanism of
      inducible chemoresistance through effects at the transcriptional and post
      translational levels.

PMID- 21189263
TI  - Involvement of protein kinase D in expression and trafficking of ATP7B (copper
      ATPase).
AB  - ATP7B is a P-type ATPase involved in copper transport and homeostasis. In
      experiments with microsomes isolated from COS-1 cells or HepG2 hepatocytes
      sustaining ATP7B heterologous expression, we found that ATP7B utilization of ATP
      includes autophosphorylation of an aspartyl residue serving as ATPase catalytic
      intermediate as well as phosphorylation of serine residues by protein kinase D
      (PKD). The latter was abolished by specific PKD inhibition with CID755673. The
      presence of PKD protein in the microsomal fraction was demonstrated by Western
      blotting. PKD is a serine/threonine kinase that associates with the trans-Golgi
      network, regulating fission of transport carriers destined to the cell surface.
      Parallel studies on cultured cells showed that nascent WT ATP7B transits to the
      Golgi complex where it undergoes serine phosphorylation by PKD. Misfolded ATP7B
      protein (especially if subjected to deletions) underwent proteasome-mediated
      degradation, which provides effective quality control. Inhibition of proteasome
      mediated degradation with MG132 yielded additional, but nonfunctional protein. On
      the other hand, serine phosphorylation protected WT ATP7B from degradation.
      Protection was enhanced by PKD activation with phorbol esters and limited by PKD
      inhibition with CID75673. As a final step, phosphorylated ATP7B was transferred
      from the Golgi complex to cytosolic trafficking vesicles. Phosphorylation and
      trafficking were completely prevented by mutations of critical copper binding
      sites, demonstrating copper dependence of both PKD-assisted phosphorylation and
      trafficking. ATP7B trafficking was markedly reduced by the Ser-478/481/1121/1453
      to Ala mutation. We conclude that PKD plays a key role in copper-dependent serine
      phosphorylation, permitting high levels of ATP7B protein expression and
      trafficking.

PMID- 21189264
TI  - Identification of a potential receptor that couples ion transport to protein
      kinase activity.
AB  - In our previous studies, we have demonstrated that the Src-coupled alpha1 Na/K
      ATPase works as a receptor for cardiotonic steroids, such as ouabain, to regulate
      cellular protein kinase cascades. Here, we explore further the structural
      determinants of the interaction between the alpha1 Na/K-ATPase and Src and
      demonstrate that the Src-coupled alpha1 Na/K-ATPase allows the cell to decode the
      transmembrane transport activity of the Na/K-ATPase to turn on/off protein
      kinases. The alpha1 Na/K-ATPase undergoes E1/E2 conformational transition during
      an ion pumping cycle. The amount of E1 and E2 Na/K-ATPase is regulated by
      extracellular K(+) and intracellular Na(+). Using purified enzyme preparations we
      find that the E1 Na/K-ATPase can bind both the Src SH2 and kinase domains
      simultaneously and keep Src in an inactive state. Conversely, the E1 to E2
      transition releases the kinase domain and activates the associated Src. Moreover,
      we demonstrate that changes in E1/E2 Na/K-ATPase by either Na(+) or K(+) are
      capable of regulating Src and Src effectors in live cells. Together, the data
      suggest that the Src-coupled alpha1 Na/K-ATPase may act as a Na(+)/K(+) receptor,
      allowing salt to regulate cellular function through Src and Src effectors.

PMID- 21189266
TI  - Prevention of 3 "never events" in the operating room: fires, gossypiboma, and
      wrong-site surgery.
AB  - BACKGROUND: This study sought to identify and provide preventative
      recommendations for potentially devastating safety violations in the operating
      room. METHODS: A Medline database search from 1950 to current using the terms
      patient safety and operating room was conducted. All topics identified were
      reviewed. Three patient safety violations with potential for immediate and
      devastating outcomes were selected for discussion using evidence-based
      literature. RESULTS: The search identified 2851 articles, 807 of which were
      directly related to patient safety in the operating room. Topics addressed by
      these 807 included infectious complications (26%), fires (11%),
      communication/teamwork (6%), retained foreign objects (3%), safety checklists
      (1%), and wrong-site surgery (1%). Fires, gossypiboma, and wrong-site surgery
      were selected for discussion. CONCLUSIONS: Although fire, gossypiboma, and wrong
      site surgery should be "never events" in the operating room, they continue to
      persist as 3 common patient safety violations. This study provides the
      epidemiology, common etiologies, and evidence-based preventative recommendations
      for each.

PMID- 21189265
TI  - Secretion of triacylglycerol-poor VLDL particles from McA-RH7777 cells expressing
      human hepatic lipase.
AB  - Hepatic lipase (HL) plays a role in the catabolism of apolipoprotein (apo)B
      containing lipoproteins through its lipolytic and ligand-binding properties. We
      describe a potential intracellular role of HL in the assembly and secretion of
      VLDL. Transient or stable expression of HL in McA-RH7777 cells resulted in
      decreased (by 40%) incorporation of [(3)H]glycerol into cell-associated and
      secreted triacylglycerol (TAG) relative to control cells. However, incorporation
      of [(35)S]methionine/cysteine into cell and medium apoB-100 was not decreased by
      HL expression. The decreased (3)H-TAG synthesis/secretion in HL expressing cells
      was not attributable to decreased expression of genes involved in lipogenesis.
      Fractionation of medium revealed that the decreased [(3)H]TAG from HL expressing
      cells was mainly attributable to decreased VLDL. Expression of catalytically
      inactive HL (HL(SG)) (Ser-145 at the catalytic site was substituted with Gly) in
      the cells also resulted in decreased secretion of VLDL-[(3)H]TAG. Examination of
      lumenal contents of microsomes showed a 40% decrease in [(3)H]TAG associated with
      lumenal lipid droplets in HL or HL(SG) expressing cells as compared with control.
      The microsomal membrane-associated [(3)H]TAG was decreased by 50% in HL
      expressing cells but not in HL(SG) expressing cells. Thus, expression of HL,
      irrespective of its lipolytic function, impairs formation of VLDL precursor
      [(3)H]TAG in the form of lumenal lipid droplets. These results suggest that HL
      expression in McA-RH7777 cells result in secretion of [(3)H]TAG-poor VLDL.

PMID- 21189267
TI  - "Gestational gigantomastia": a review article and case presentation of a new
      surgical management option.
AB  - BACKGROUND: Gestational gigantomastia is a nightmare to pregnant women. The
      currently available surgical intervention is either reduction mammoplasty or
      simple mastectomy. Reduction mammoplasty carries high risk of recurrence. Simple
      mastectomy is a mutilating option for a benign condition. METHODS: A thorough
      literature research was performed for all reported gestational gigantomastia
      cases. In addition, this study presents a case that was diagnosed and treated at
      the authors' center. RESULTS: The patients' age mean age was 26.8 years. Surgical
      intervention is the only currently available curative option. The authors were
      able to introduce an alternative surgical technique: bilateral subcutaneous
      mastectomy (BSCM) with latissimus dorsi muscle flaps (LDF) and free nipple areola
      complex grafting (FNAG). CONCLUSION: Despite being a benign condition,
      gestational gigantomastia could turn to be a catastrophe. BSCM with LDF and FNAG
      represents an excellent alternative breast saving surgical option. It offers the
      advantage of restoring normal breast shape with no fear of future recurrences.

PMID- 21189268
TI  - No visible scar (NVIS) colectomy: a new approach to minimal access surgery to the
      colon.
AB  - INTRODUCTION: Minimally invasive surgery continues to revolutionize surgical
      standards with trends toward further minimalization and improved cosmesis.
      Approaches such as laparoendoscopic single-site surgery (LESS) and natural
      orifice translumenal endoscopic surgery (NOTES) have thus emerged. The authors
      devised an alternative method for a more efficient approach to minimally invasive
      surgery called no visible scar (NVIS). This study describes NVIS and its ability
      to provide operative capacity and outcomes similar to other minimal access
      techniques, but with improved cosmesis and possibly decreased associated
      complications. METHODS: This is a retrospective analysis of patients undergoing
      colectomy between June 2009 and March 2010 to evaluate our outcomes with the NVIS
      technique (surgical approach via a 4-5 cm suprapubic site for inserting
      trocars/multiport and specimen extraction, with a 5-mm umbilical incision for a
      single trocar). Outcome measures included intraoperative complications,
      postoperative morbidity, and cosmetic outcome. RESULTS: Ten patients with a mean
      age of 60.3 years underwent NVIS colectomy. The average operating time was 161.3
      minutes with a mean blood loss of 56.5 mL. There were no conversions to open
      surgery. One patient required additional trocar placement. No perioperative
      complications were encountered. On follow-up, no wound complications were noted
      and all patients appeared satisfied with their cosmetic outcome. One patient was
      readmitted for a low-grade fever, but the NVIS technique was not identified as a
      contributor. CONCLUSION: NVIS is a safe and feasible minimal access alternative,
      which improves cosmesis and may decrease complications associated with other
      minimally invasive techniques. Further analysis in a larger patient population is
      warranted to support our findings.

PMID- 21189269
TI  - Effects of the allosteric antagonist 1-(4-chlorophenyl)-3-[3-(6-pyrrolidin-1
      ylpyridin-2-yl)phenyl]urea (PSNCBAM-1) on CB1 receptor modulation in the
      cerebellum.
AB  - 1-(4-Chlorophenyl)-3-[3-(6-pyrrolidin-1-ylpyridin-2-yl)phenyl] urea (PSNCBAM-1)
      has recently been described as a cannabinoid CB1 receptor allosteric antagonist
      associated with hypophagic effects in vivo; however, PSNCBAM-1 effects on CB(1)
      ligand-mediated modulation of neuronal excitability remain unknown. Here, we
      investigate PSNCBAM-1 actions on CB(1) receptor-stimulated guanosine 5'-O-(3
      [(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding in cerebellar membranes and
      on CB(1) ligand modulation of presynaptic CB(1) receptors at inhibitory
      interneuron-Purkinje cell synapses in the cerebellum using whole-cell
      electrophysiology. PSNCBAM-1 caused noncompetitive antagonism in [(35)S]GTPgammaS
      binding studies, with higher potency against the CB receptor agonist (-)-cis-3-[2
      hydroxy-4-(1,1-dimethyl heptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol
      (CP55940) than for R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]
      pyrrolo[1,2,3,-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate]
      [WIN55,212-2 (WIN55)]. In electrophysiological studies, WIN55 and CP55940 reduced
      miniature inhibitory postsynaptic currents (mIPSCs) frequency but not amplitude.
      PSNCBAM-1 application alone had no effect on mIPSCs; however, PSNCBAM-1
      pretreatment revealed agonist-dependent functional antagonism, abolishing CP55940
      induced reductions in mIPSC frequency but having no clear effect on WIN55
      actions. The CB(1) antagonist/inverse agonist N-(piperidin-1-yl)-1-(2,4
      dichlorophenyl)-5-(4-iodophenyl)-4-methyl-1H-multipyrazole-3-carboxamide (AM251)
      increased mIPSC frequency beyond control; this effect was reversed by PSNCBAM-1.
      PSNCBAM-1 pretreatment also attenuated AM251 effects. Thus, PSNCBAM-1 reduced
      CB(1) receptor ligand functional efficacy in the cerebellum. The differential
      effect of PSNCBAM-1 on CP55940 versus WIN55 actions in [(35)S]GTPgammaS binding
      and electrophysiological studies and the attenuation of AM251 effects are
      consistent with the ligand-dependence associated with allosteric modulation.
      These data provide the first description of functional PSNCBAM-1 allosteric
      antagonist effects on neuronal excitability in the mammalian central nervous
      system (CNS). PSNCBAM-1 allosteric antagonism may provide viable therapeutic
      alternatives to orthosteric CB(1) antagonists/inverse agonists in the treatment
      of CNS disease.

PMID- 21189270
TI  - Comparison of oral amoxicillin with placebo for the treatment of world health
      organization-defined nonsevere pneumonia in children aged 2-59 months: a
      multicenter, double-blind, randomized, placebo-controlled trial in pakistan.
AB  - BACKGROUND: world Health Organization (WHO) acute respiratory illness case
      management guidelines classify children with fast breathing as having pneumonia
      and recommend treatment with an antibiotic. There is concern that many of these
      children may not have pneumonia and are receiving antibiotics unnecessarily. This
      could increase antibiotic resistance in the community. The aim was to compare the
      clinical outcome at 72 h in children with WHO-defined nonsevere pneumonia when
      treated with amoxicillin, compared with placebo. METHODS: we performed a double
      blind, randomized, equivalence trial in 4 tertiary hospitals in Pakistan. Nine
      hundred children aged 2-59 months with WHO defined nonsevere pneumonia were
      randomized to receive either 3 days of oral amoxicillin (45mg/kg/day) or placebo;
      873 children completed the study. All children were followed up on days 3, 5, and
      14. The primary outcome was therapy failure defined a priori at 72 h. RESULTS: in
      per-protocol analysis at day 3, 31 (7.2%) of the 431 children in the amoxicillin
      arm and 37 (8.3%) of the 442 in placebo group had therapy failure. This
      difference was not statistically significant (odds ratio [OR], .85; 95%CI, .50
      1.43; P = .60). The multivariate analysis identified history of difficult
      breathing (OR, 2.86; 95% CI, 1.29-7.23; P = .027) and temperature >37.5 degrees C
      100 degrees F at presentation (OR, 1.99; 95% CI, 1.37-2.90; P = .0001) as risk
      factors for treatment failure by day 5. CONCLUSION: clinical outcome in children
      aged 2-59 months with WHO-defined nonsevere pneumonia is not different when
      treated with an antibiotic or placebo. Similar trials are needed in countries
      with a high burden of pneumonia to rationalize the use of antibiotics in these
      communities.

PMID- 21189271
TI  - Development of cytomegalovirus (CMV) immune recovery uveitis is associated with
      Th17 cell depletion and poor systemic CMV-specific T cell responses.
AB  - BACKGROUND: the immune reconstitution inflammatory syndromes (IRIS) are a
      spectrum of inflammatory conditions associated with opportunistic infections and
      occurring in approximately16% of human immunodeficiency type 1 (HIV-1)-infected
      patients given antiretroviral therapy. It has been proposed that these conditions
      are linked by a dysregulated immune system that is prone to exaggerated
      responses. However, immunologic studies have been limited by the availability of
      longitudinal samples from patients with IRIS and appropriate matched control
      subjects. Cytomegalovirus (CMV) immune recovery uveitis (IRU) is an IRIS
      occurring in up to 38% of patients with CMV retinitis. Although the pathologic
      immune responses occur in the eye, immune dysregulation that allows for
      development of pathologic responses is presumably caused by faulty systemic
      immune cell reconstitution. METHODS: we examined CMV-specific T cell responses,
      regulatory T (T(reg)) cell function and polyclonal T cell responses, including IL
      17 production, in 25 patients with CMV IRU and 49 immunorestored control subjects
      with CMV retinitis who did not develop IRU. RESULTS: patients with CMV IRU had
      poor CMV-specific CD4(+) T cell responses, as compared with control subjects,
      whereas CD8(+) T cell responses were comparable. Patients with CMV IRU were
      characterized by smaller numbers of circulating Th17 cells. Deficiency in anti
      CMV responses was not associated with differences in T(reg) cell function.
      CONCLUSIONS: the T(reg) cell compartment is intact in patients with CMV IRU, and
      these patients do not develop exaggerated systemic CMV-specific or polyclonal
      immune responses. Cases are instead characterized by more profound depletion of
      Th17 cells and poor antiviral immune responses. CMV IRU may be most likely to
      develop in persons experiencing the greatest degree of immune dysfunction before
      initiating highly active antiretroviral therapy.

PMID- 21189272
TI  - A review of death certificates listing Lyme disease as a cause of death in the
      United States.
AB  - Lyme disease was listed as an underlying or multiple cause of death on 114 death
      records during 1999-2003. Upon review, only 1 record was consistent with clinical
      manifestations of Lyme disease. This analysis indicates that Lyme disease is rare
      as a cause of death in the United States.

PMID- 21189274
TI  - Nonfasting lipids, lipoproteins, and apolipoproteins in individuals with and
      without diabetes: 58 434 individuals from the Copenhagen General Population
      Study.
AB  - BACKGROUND: Whether lipid profiles should be collected from fasting or nonfasting
      individuals is controversial, particularly in the diabetic population. We
      examined the influence of normal food intake on lipid profiles in diabetic and
      nondiabetic individuals. METHODS: We assessed plasma concentrations of lipids,
      lipoproteins, apolipoproteins, and albumin as a function of time since the last
      meal in 58 434 individuals (participation rate 45%) from the general population,
      2270 of whom had diabetes mellitus. RESULTS: Similar patterns in the measured
      constituents were observed in the diabetic and nondiabetic populations.
      Triglycerides remained increased for 6-7 h in both populations after the last
      meal, whereas LDL cholesterol and albumin but not apolipoprotein B were reduced
      in both populations up to 5 h after normal food intake; after adjustment for
      hemodilution on the basis of albumin concentrations, the LDL cholesterol
      reductions were no longer present. Maximum observed mean differences from fasting
      concentrations in diabetic patients were -0.6 mmol/L, 0 mmol/L, 0.2 mmol/L, and
      0.08 g/L (8 mg/dL) for LDL cholesterol, HDL cholesterol, triglycerides, and
      apolipoprotein B, respectively, and, correspondingly, -0.3 mmol/L, 0 mmol/L, 0.2
      mmol/L, and 0.03 g/L (3 mg/dL) in individuals without diabetes. CONCLUSIONS:
      Triglycerides increased up to 0.2 mmol/L after normal food intake in individuals
      with and without diabetes, whereas the postprandial reductions in LDL cholesterol
      observed in both populations likely were caused by hemodilution due to fluid
      intake. No statistically significant differences in postprandial apolipoprotein B
      concentrations were found. These data may be useful for discussion during
      revisions of guidelines for lipid measurements in individuals with or without
      diabetes.

PMID- 21189273
TI  - Comparative Effectiveness and Toxicity of Statins Among HIV-Infected Patients.
AB  - BACKGROUND: dyslipidemia is common and is often treated with 3-hydroxy-3
      methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins). Little is
      known about the comparative effectiveness of statins among human immunodeficiency
      virus (HIV)-infected patients. This study compared the effectiveness and toxicity
      of statins among HIV-infected patients in clinical care. METHODS: we conducted a
      retrospective cohort study of patients starting their initial statin medications
      at 2 large HIV clinics (N = 700). The primary observation was change in lipid
      levels during statin therapy. Secondary observations included whether
      individualized National Cholesterol Education Program (NCEP) goals for low
      density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein
      cholesterol (non-HDL-C) levels were reached, and toxicity rates. We used linear
      regression to examine change in lipid levels, controlling for baseline lipid
      values and demographic and clinical characteristics. We conducted secondary
      analyses using propensity scores to address confounding by indication. RESULTS:
      the most commonly prescribed statins were atorvastatin (N = 303), pravastatin (N
      = 280), and rosuvastatin (N = 95). One year after starting a statin therapy,
      patients who received atorvastatin or rosuvastatin had significantly greater
      decreases in total cholesterol, LDL-C, and non-HDL-C than patients on
      pravastatin. The likelihood of reaching NCEP goals for LDL-C levels was higher
      with the use of rosuvastatin (OR 2.1; P = .03) and atorvastatin (odds ratio [OR],
      2.1; P = .001) compared with that of pravastatin. The likelihood of reaching NCEP
      goals for non-HDL-C levels was higher for rosuvastatin (OR 2.3; P = .045) but not
      atorvastatin (OR, 1.5; P = .1) compared with pravastatin. Toxicity rates were
      similar for all 3 statins: 7.3% for atorvastatin, 6.1% for pravastatin, and 5.3%
      for rosuvastatin. CONCLUSIONS: our findings suggest that atorvastatin and
      rosuvastatin are preferable to pravastatin for treatment of HIV-infected patients
      with dyslipidemia, due to greater declines in total cholesterol, LDL-C, and non
      HDL-C, with similar lower toxicity rates.

PMID- 21189275
TI  - Urinary catalytic iron in obesity.
AB  - INTRODUCTION: Obesity precedes the development of many cardiovascular disease
      risk factors, including type 2 diabetes mellitus (DM), hypertension, and chronic
      kidney disease. Catalytic iron, which has been associated with these chronic
      diseases, may be one of the links between obesity and these multifactorial
      diverse disorders. OBJECTIVE: We investigated whether urinary catalytic iron is
      increased in obese individuals without DM and overt kidney disease. STUDY DESIGN:
      We measured urinary catalytic iron using established methods in 200 randomly
      selected individuals without DM [100 who were obese (body mass index >=30
      kg/m(2)) and 100 who were nonobese (body mass index <=27)]. Participants were
      selected from an outpatient clinic and community setting and were part of an
      ongoing cross-sectional study of obesity in individuals between the ages of 18
      and 70 years. RESULTS: There was a significant difference in mean (95% CI)
      urinary catalytic iron excretion between the obese participants and the nonobese
      participants, 463 (343-582) nmol/mg [52.3 (38.8-65.8) nmol/MUmol] vs 197 (141
      253) nmol/mg [22.3 (15.9-28.6) nmol/MUmol]; P < 0.001. The significant predictors
      of increased urinary catalytic iron were obesity (P = 0.001) and waist-to-hip
      ratio (P = 0.03). CONCLUSIONS: Our study results demonstrate that obesity and
      waist-to-hip ratio are associated with increased urinary catalytic iron, which
      may be a useful marker of oxidative stress. Additional studies are needed to
      determine the role of catalytic iron in increased cardiovascular disease and
      chronic kidney disease associated with obesity.

PMID- 21189276
TI  - Persistently increased acetaminophen concentrations in a patient with acute liver
      failure.

PMID- 21189277
TI  - Commentary.

PMID- 21189278
TI  - Commentary.

PMID- 21189284
TI  - Transducin beta-like protein 1 recruits nuclear factor kappaB to the target gene
      promoter for transcriptional activation.
AB  - Nuclear factor kappaB (NF-kappaB) signaling controls a wide range of cellular
      functions such as tumor progression and invasion by inducing gene expression.
      Upon stimulation, NF-kappaB is translocated to the nucleus and binds to its
      target gene promoters to activate transcription by recruiting transcription
      coactivators. Although significant progress has been made in understanding NF
      kappaB-mediated transactivation, little is known about how NF-kappaB is recruited
      to its target gene promoters. Here, we report that transducin beta-like protein 1
      (TBL1) controls the expression of NF-kappaB target genes by directly binding with
      NF-kappaB and facilitating its recruitment to target gene promoters. Tumor
      necrosis factor alpha stimulation triggered the formation of an NF-kappaB and
      TBL1 complex and subsequent target gene promoter binding. Knockdown of TBL1
      impaired the recruitment of NF-kappaB to its target gene promoters.
      Interestingly, analysis of the Oncomine database revealed that TBL1 mRNA levels
      were significantly higher in invasive breast cancer tissues than in breast
      adenocarcinoma tissue. Consistently, TBL1 knockdown significantly reduced the
      invasive potential of breast cancer cells by inhibiting NF-kappaB. Our results
      reveal a new mechanism for the regulation of NF-kappaB activation, with important
      implications for the development of novel strategies for cancer therapy by
      targeting NF-kappaB.

PMID- 21189285
TI  - Characterization of the core elements of the NF-kappaB signaling pathway of the
      sea anemone Nematostella vectensis.
AB  - The sea anemone Nematostella vectensis is the leading developmental and genomic
      model for the phylum Cnidaria, which includes anemones, hydras, jellyfish, and
      corals. In insects and vertebrates, the NF-kappaB pathway is required for
      cellular and organismal responses to various stresses, including pathogens and
      chemicals, as well as for several developmental processes. Herein, we have
      characterized proteins that comprise the core NF-kappaB pathway in Nematostella,
      including homologs of NF-kappaB, IkappaB, Bcl-3, and IkappaB kinase (IKK). We
      show that N. vectensis NF-kappaB (Nv-NF-kappaB) can bind to kappaB sites and
      activate transcription of reporter genes containing multimeric kappaB sites or
      the Nv-IkappaB promoter. Both Nv-IkappaB and Nv-Bcl-3 interact with Nv-NF-kappaB
      and block its ability to activate reporter gene expression. Nv-IKK is most
      similar to human IKKepsilon/TBK kinases and, in vitro, can phosphorylate Ser47 of
      Nv-IkappaB. Nv-NF-kappaB is expressed in a subset of ectodermal cells in juvenile
      and adult Nematostella anemones. A bioinformatic analysis suggests that homologs
      of many mammalian NF-kappaB target genes are targets for Nv-NF-kappaB, including
      genes involved in apoptosis and responses to organic compounds and endogenous
      stimuli. These results indicate that NF-kappaB pathway proteins in Nematostella
      are similar to their vertebrate homologs, and these results also provide a
      framework for understanding the evolutionary origins of NF-kappaB signaling.

PMID- 21189286
TI  - Increased Akt-mTOR signaling in lung epithelium is associated with respiratory
      distress syndrome in mice.
AB  - Pregnancy in women with diabetes is associated with a higher risk of perinatal
      complications. In particular, infants of diabetic mothers frequently suffer from
      respiratory distress syndrome (RDS), which is a leading cause of death in preterm
      infants and is considered to be primarily due to hyperinsulinemia in infants in
      response to maternal hyperglycemia. To elucidate the mechanism of how insulin
      signaling induces RDS, bronchoalveolar epithelium-specific Akt1 transgenic (TG)
      mice were generated. Akt1 overexpression in fetal lung epithelium resulted in RDS
      in preterm infants born by Caesarean section at embryonic day 18.5 (E18.5). The
      expression levels of hypoxia-inducible factor 2alpha (HIF-2alpha) and its target
      vascular endothelial growth factor (VEGF) were downregulated in the lung of Akt1
      TG mice. Inhibition of the Akt-mammalian target of rapamycin (mTOR) signaling
      axis by rapamycin restored the expression of VEGF and improved the lung pathology
      of Akt1 TG pups. Rapamycin also attenuated the RDS phenotype in wild-type mice
      delivered preterm at E17.5. In cultured lung epithelial cells, insulin reduced
      VEGF expression and transcriptional activity of HIF-2 on VEGF promoter in an mTOR
      dependent manner. Thus, aberrant activation of the Akt-mTOR pathway in lung
      epithelium plays a causal role in the pathogenesis of infant RDS, presumably
      through downregulation of HIF-2-dependent VEGF expression in the lung.

PMID- 21189287
TI  - TIA1 prevents skipping of a critical exon associated with spinal muscular
      atrophy.
AB  - Prevention of skipping of exon 7 during pre-mRNA splicing of Survival Motor
      Neuron 2 (SMN2) holds the promise for cure of spinal muscular atrophy (SMA), a
      leading genetic cause of infant mortality. Here, we report T-cell-restricted
      intracellular antigen 1 (TIA1) and TIA1-related (TIAR) proteins as intron
      associated positive regulators of SMN2 exon 7 splicing. We show that TIA1/TIAR
      stimulate exon recognition in an entirely novel context in which intronic U-rich
      motifs are separated from the 5' splice site by overlapping inhibitory elements.
      TIA1 and TIAR are modular proteins with three N-terminal RNA recognition motifs
      (RRMs) and a C-terminal glutamine-rich (Q-rich) domain. Our results reveal that
      any one RRM in combination with a Q domain is necessary and sufficient for TIA1
      associated regulation of SMN2 exon 7 splicing in vivo. We also show that
      increased expression of TIA1 counteracts the inhibitory effect of polypyrimidine
      tract binding protein, a ubiquitously expressed factor recently implicated in
      regulation of SMN exon 7 splicing. Our findings expand the scope of TIA1/TIAR in
      genome-wide regulation of alternative splicing under normal and pathological
      conditions.

PMID- 21189288
TI  - Phosphorylation of Trask by Src kinases inhibits integrin clustering and
      functions in exclusion with focal adhesion signaling.
AB  - Trask is a recently described transmembrane substrate of Src kinases whose
      expression and phosphorylation has been correlated with the biology of some
      cancers. Little is known about the molecular functions of Trask, although its
      phosphorylation has been associated with cell adhesion. We have studied the
      effects of Trask phosphorylation on cell adhesion, integrin activation,
      clustering, and focal adhesion signaling. The small hairpin RNA (shRNA) knockdown
      of Trask results in increased cell adhesiveness and a failure to properly
      inactivate focal adhesion signaling, even in the unanchored state. On the
      contrary, the experimentally induced phosphorylation of Trask results in the
      inhibition of cell adhesion and inhibition of focal adhesion signaling. This is
      mediated through the inhibition of integrin clustering without affecting integrin
      affinity state or ligand binding activity. Furthermore, Trask signaling and focal
      adhesion signaling inactivate each other and signal in exclusion with each other,
      constituting a switch that underlies cell anchorage state. These data provide
      considerable insight into how Trask functions to regulate cell adhesion and
      reveal a novel pathway through which Src kinases can oppose integrin-mediated
      cell adhesion.

PMID- 21189289
TI  - HEB-deficient T-cell precursors lose T-cell potential and adopt an alternative
      pathway of differentiation.
AB  - Early thymocytes possess multilineage potential, which is progressively
      restricted as cells transit through the double-negative stages of T-cell
      development. DN1 cells retain the ability to become natural killer cells,
      dendritic cells, B cells, and myeloid cells as well as T cells, but these options
      are lost by the DN3 stage. The Notch1 signaling pathway is indispensable for
      initiation of the T-cell lineage and inhibitory for the B-cell lineage, but the
      regulatory mechanisms by which the T-cell fate is locked in are largely
      undefined. Previously, we discovered that the E-protein transcription factor
      HEBAlt promoted T-cell specification. Here, we report that HEB(-/-) T-cell
      precursors have compromised Notch1 function and lose T-cell potential. Moreover,
      reconstituting HEB(-/-) precursors with Notch1 activity enforced fidelity to the
      T-cell fate. However, instead of becoming B cells, HEB(-/-) DN3 cells adopted a
      DN1-like phenotype and could be induced to differentiate into thymic NK cells.
      HEB(-/-) DN1-like cells retained GATA3 and Id2 expression but had lower levels of
      the Bcl11b gene, a Notch target gene. Therefore, our studies have revealed a new
      set of interactions between HEB, Notch1, and GATA3 that regulate the T-cell fate
      choice in developing thymocytes.

PMID- 21189290
TI  - Compartmentalized Ras proteins transform NIH 3T3 cells with different
      efficiencies.
AB  - Ras GTPases were long thought to function exclusively from the plasma membrane
      (PM). However, a current model suggests that Ras proteins can compartmentalize to
      regulate different functions, and an oncogenic H-Ras mutant that is restricted to
      the endomembrane can still transform cells. In this study, we demonstrated that
      cells transformed by endomembrane-restricted oncogenic H-Ras formed tumors in
      nude mice. To define downstream targets of endomembrane Ras pathways, we analyzed
      Cdc42, which concentrates in the endomembrane and has been shown to act
      downstream of Ras in Schizosaccharomyces pombe. Our data show that cell
      transformation induced by endomembrane-restricted oncogenic H-Ras was blocked
      when Cdc42 activity was inhibited. Moreover, H-Ras formed a complex with Cdc42 on
      the endomembrane, and this interaction was enhanced when H-Ras was GTP bound or
      when cells were stimulated by growth factors. H-Ras binding evidently induced
      Cdc42 activation by recruiting and/or activating Cdc42 exchange factors. In
      contrast, when constitutively active H-Ras was restricted to the PM by fusing to
      a PM localization signal from the Rit GTPase, the resulting protein did not
      detectably activate Cdc42 although it activated Raf-1 and efficiently induced
      hallmarks of Ras-induced senescence in human BJ foreskin fibroblasts.
      Surprisingly, PM-restricted oncogenic Ras when expressed alone could only weakly
      transform NIH 3T3 cells; however, when constitutively active Cdc42 was
      coexpressed, together they transformed cells much more efficiently than either
      one alone. These data suggest that efficient cell transformation requires Ras
      proteins to interact with Cdc42 on the endomembrane and that in order for a given
      Ras protein to fully transform cells, multiple compartment-specific Ras pathways
      need to work cooperatively.

PMID- 21189292
TI  - Data are cumulating about elevated troponin I levels in asymptomatic dialysis
      patients.

PMID- 21189291
TI  - Role for cohesin in the formation of a heterochromatic domain at fission yeast
      subtelomeres.
AB  - Increasing evidence implicates cohesin in the control of gene expression. Here we
      report the first analysis of cohesin-dependent gene regulation in fission yeast.
      Global expression profiling of the mis4-367 cohesin loader mutant identified a
      small number of upregulated and downregulated genes within subtelomeric domains
      (SD). These 20- to 40-kb regions between chromosome arm euchromatin and telomere
      proximal heterochromatin are characterized by a combination of euchromatin
      (methylated lysine 4 on histone H3/methylated Tysine 9 on histone H3 [H3K4me])
      and heterochromatin (H3K9me) marks. We focused our analysis on the chromosome 1
      right SD, which contains several upregulated genes and is bordered on the
      telomere-distal side by a pair of downregulated genes. We find that the
      expression changes in the SD also occur in a mutant of the cohesin core component
      Rad21. Remarkably, mutation of Rad21 results in the depletion of Swi6 binding in
      the SD. In fact, the Rad21 mutation phenocopied Swi6 loss of function: both
      mutations led to reduced cohesin binding, reduced H3K9me, and similar gene
      expression changes in the SD. In particular, expression of the gene pair
      bordering the SD was dependent both on cohesin and on Swi6. Our data indicate
      that cohesin participates in the setup of a subtelomeric heterochromatin domain
      and controls the expression of the genes residing in that domain.

PMID- 21189293
TI  - Phosphoinositides regulate clathrin-dependent endocytosis at the tip of pollen
      tubes in Arabidopsis and tobacco.
AB  - Using the tip-growing pollen tube of Arabidopsis thaliana and Nicotiana tabacum
      as a model to investigate endocytosis mechanisms, we show that
      phosphatidylinositol-4-phosphate 5-kinase 6 (PIP5K6) regulates clathrin-dependent
      endocytosis in pollen tubes. Green fluorescent protein-tagged PIP5K6 was
      preferentially localized to the subapical plasma membrane (PM) in pollen tubes
      where it apparently converts phosphatidylinositol 4-phosphate (PI4P) to
      phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)]. RNA interference-induced
      suppression of PIP5K6 expression impaired tip growth and inhibited clathrin
      dependent endocytosis in pollen tubes. By contrast, PIP5K6 overexpression induced
      massive aggregation of the PM in pollen tube tips. This PM abnormality was
      apparently due to excessive clathrin-dependent membrane invagination because this
      defect was suppressed by the expression of a dominant-negative mutant of clathrin
      heavy chain. These results support a role for PI(4,5)P(2) in promoting early
      stages of clathrin-dependent endocytosis (i.e., membrane invagination).
      Interestingly, the PIP5K6 overexpression-induced PM abnormality was partially
      suppressed not only by the overexpression of PLC2, which breaks down PI(4,5)P(2),
      but also by that of PI4Kbeta1, which increases the pool of PI4P. Based on these
      observations, we propose that a proper balance between PI4P and PI(4,5)P(2) is
      required for clathrin-dependent endocytosis in the tip of pollen tubes.

PMID- 21189294
TI  - Identification and characterization of nuclear pore complex components in
      Arabidopsis thaliana.
AB  - The nuclear pore complex (NPC) facilitates nucleocytoplasmic transport, a crucial
      process for various cellular activities. The NPC comprises ~30 nucleoporins and
      is well characterized in vertebrates and yeast. However, only eight plant
      nucleoporins have been identified, and little information is available about the
      complete molecular structure of plant NPCs. In this study, an interactive
      proteomic approach was used to identify Arabidopsis thaliana nucleoporins. A
      series of five cycles of interactive proteomic analysis was performed using green
      fluorescent protein (GFP)-tagged nucleoporins. The identified nucleoporins were
      then cloned and subcellular localization analyses were performed. We found that
      the plant NPC contains at least 30 nucleoporins, 22 of which had not been
      previously annotated. Surprisingly, plant nucleoporins shared a similar domain
      organization to their vertebrate (human) and yeast (Saccharomyces cerevisiae)
      counterparts. Moreover, the plant nucleoporins exhibited higher sequence homology
      to vertebrate nucleoporins than to yeast nucleoporins. Plant NPCs lacked seven
      components (NUCLEOPORIN358 [Nup358], Nup188, Nup153, Nup45, Nup37, NUCLEAR
      DIVISION CYCLE1, and PORE MEMBRANE PROTEIN OF 121 kD) that were present in
      vertebrate NPCs. However, plants possessed a nucleoporin, Nup136/Nup1, that
      contained Phe-Gly repeats, and sequence analysis failed to identify a vertebrate
      homolog for this protein. Interestingly, Nup136-GFP showed greater mobility on
      the nuclear envelope than did other nucleoporins, and a Nup136/Nup1 deficiency
      caused various defects in plant development. These findings provide valuable new
      information about plant NPC structure and function.

PMID- 21189296
TI  - Blind attraction: the mechanism of an inherited congenital cataract.

PMID- 21189297
TI  - Who's who in human recombination: BRCA2 and RAD52.

PMID- 21189298
TI  - Disruption of small RNA signaling caused by competition for Hfq.
AB  - Small RNAs (sRNAs) regulate diverse pathways, including stress responses,
      virulence, and metabolism in Escherichia coli. At the center of this large sRNA
      regulatory network is the Hfq protein. Hfq mediates the binding of sRNAs to their
      target mRNAs; without Hfq, most sRNAs cannot efficiently regulate target mRNA
      expression. Here, we show in vivo that Hfq can be a limiting factor for sRNA
      activity and that it can be easily depleted, causing disruption of the sRNA
      network. Depletion of the available Hfq can occur when sRNAs and target mRNAs are
      transcribed at high levels without their partners, resulting in the sequestration
      of Hfq into sRNA-Hfq and target mRNA-Hfq complexes. This can be avoided by
      coordinating the transcription of sRNAs with their target mRNAs so that they are
      turned on and off together to maximize duplex formation and minimize Hfq
      sequestration. Therefore, the limited availability of Hfq results in a highly
      interdependent sRNA network, wherein the activity of each sRNA depends on the
      activity of the other sRNAs and target mRNAs in the network.

PMID- 21189299
TI  - Immature T-cell clustering and efficient differentiation require the polarity
      protein Scribble.
AB  - T-cell polarization is required for cell migration and cell-cell interactions,
      cellular behaviors crucial for lymphocyte differentiation. Despite expression of
      the epithelial polarity network in T cells, neither its contribution to thymocyte
      polarity nor its requirement during development is known. We report here that
      depletion of the polarity protein Scribble in hematopoietic progenitor cells
      results in inefficient T-cell development characterized by a partial
      developmental block during the early double-negative (DN) stage of
      differentiation. Scribble-depleted hematopoietic progenitor cells exhibit a
      delayed transition into late CD44(lo/-)CD25(+) DN3 cells, evidenced by the
      accumulation of early CD44(int)CD25(+) DN3 cells. As a consequence, a limited
      cellular expansion and a reduced frequency of intracellular T-cell receptor beta
      positive DN3 cells are observed among Scribble-deficient differentiating T cells.
      Moreover, whereas purified Scribble-depleted DN2 and DN3 cells do not exhibit
      compromised spontaneous motility, T-cell clustering and prolonged homotypic
      interactions among such cells are reduced. This deficiency correlates with a lack
      of polarization of the integrin LFA-1 during T-cell migration or on the
      initiation of T-cell-T-cell interactions. Scribble is therefore a critical
      contributor to the clustering of immature T cells, an event shown here to be
      necessary for efficient developmental progression.

PMID- 21189300
TI  - Colonization of high altitudes by alien plants over the last two centuries.

PMID- 21189301
TI  - Genetic signals of origin, spread, and introgression in a large sample of maize
      landraces.
AB  - The last two decades have seen important advances in our knowledge of maize
      domestication, thanks in part to the contributions of genetic data. Genetic
      studies have provided firm evidence that maize was domesticated from Balsas
      teosinte (Zea mays subspecies parviglumis), a wild relative that is endemic to
      the mid- to lowland regions of southwestern Mexico. An interesting paradox
      remains, however: Maize cultivars that are most closely related to Balsas
      teosinte are found mainly in the Mexican highlands where subspecies parviglumis
      does not grow. Genetic data thus point to primary diffusion of domesticated maize
      from the highlands rather than from the region of initial domestication. Recent
      archeological evidence for early lowland cultivation has been consistent with the
      genetics of domestication, leaving the issue of the ancestral position of
      highland maize unresolved. We used a new SNP dataset scored in a large number of
      accessions of both teosinte and maize to take a second look at the geography of
      the earliest cultivated maize. We found that gene flow between maize and its wild
      relatives meaningfully impacts our inference of geographic origins. By analyzing
      differentiation from inferred ancestral gene frequencies, we obtained results
      that are fully consistent with current ecological, archeological, and genetic
      data concerning the geography of early maize cultivation.

PMID- 21189304
TI  - A scaling theory for the size distribution of emitted dust aerosols suggests
      climate models underestimate the size of the global dust cycle.
AB  - Mineral dust aerosols impact Earth's radiation budget through interactions with
      clouds, ecosystems, and radiation, which constitutes a substantial uncertainty in
      understanding past and predicting future climate changes. One of the causes of
      this large uncertainty is that the size distribution of emitted dust aerosols is
      poorly understood. The present study shows that regional and global circulation
      models (GCMs) overestimate the emitted fraction of clay aerosols (< 2 MUm
      diameter) by a factor of ~2-8 relative to measurements. This discrepancy is
      resolved by deriving a simple theoretical expression of the emitted dust size
      distribution that is in excellent agreement with measurements. This expression is
      based on the physics of the scale-invariant fragmentation of brittle materials,
      which is shown to be applicable to dust emission. Because clay aerosols produce a
      strong radiative cooling, the overestimation of the clay fraction causes GCMs to
      also overestimate the radiative cooling of a given quantity of emitted dust. On
      local and regional scales, this affects the magnitude and possibly the sign of
      the dust radiative forcing, with implications for numerical weather forecasting
      and regional climate predictions in dusty regions. On a global scale, the dust
      cycle in most GCMs is tuned to match radiative measurements, such that the
      overestimation of the radiative cooling of a given quantity of emitted dust has
      likely caused GCMs to underestimate the global dust emission rate. This implies
      that the deposition flux of dust and its fertilizing effects on ecosystems may be
      substantially larger than thought.

PMID- 21189302
TI  - Microenvironmental control of malignancy exerted by RNASET2, a widely conserved
      extracellular RNase.
AB  - A recent body of evidence indicates an active role for stromal (mis)-regulation
      in the progression of neoplasias. Within this conceptual framework, genes
      belonging to the growing but still poorly characterized class of tumor
      antagonizing/malignancy suppressor genes (TAG/MSG) seem to play a crucial role in
      the regulation of the cross-talk between stromal and epithelial cells by
      controlling malignant growth in vivo without affecting any cancer-related
      phenotype in vitro. Here, we have functionally characterized the human RNASET2
      gene, which encodes the first human member of the widespread Rh/T2/S family of
      extracellular RNases and was recently found to be down-regulated at the
      transcript level in several primary ovarian tumors or cell lines and in melanoma
      cell lines. Although we could not detect any activity for RNASET2 in several
      functional in vitro assays, a remarkable control of ovarian tumorigenesis could
      be detected in vivo. Moreover, the control of ovarian tumorigenesis mediated by
      this unique tumor suppressor gene occurs through modification of the cellular
      microenvironment and the induction of immunocompetent cells of the
      monocyte/macrophage lineage. Taken together, the data presented in this work
      strongly indicate RNASET2 as a previously unexplored member of the growing family
      of tumor-antagonizing genes.

PMID- 21189306
TI  - Diabetes management at school: application of the healthy learner model.
AB  - Every child with diabetes deserves a school nurse with the capacity to
      effectively manage the disease at school. The school nurse needs knowledge and
      skills to confidently provide care and communicate with health care providers and
      families. The Healthy Learner Model for Chronic Condition Management provided a
      framework to eliminate the disjointed approach to diabetes management at school,
      replacing it with a consistent, evidence-based approach. A diabetes resource
      nurse was a key component, providing support for the school nurse and
      collaboration between the school, community, family, and health care providers.
      Funded by a cooperative agreement from the Centers for Disease Control and
      Prevention (CDC), the National Association of School Nurses (NASN) chose five
      sites from across the country to implement this program-a project titled Managing
      and Preventing Diabetes and Weight Gain (MAP). This article describes the
      experience of two sites.

PMID- 21189303
TI  - Complex genetic, photothermal, and photoacoustic analysis of nanoparticle-plant
      interactions.
AB  - Understanding the nature of interactions between engineered nanomaterials and
      plants is crucial in comprehending the impact of nanotechnology on the
      environment and agriculture with a focus on toxicity concerns, plant disease
      treatment, and genetic engineering. To date, little progress has been made in
      studying nanoparticle-plant interactions at single nanoparticle and genetic
      levels. Here, we introduce an advanced platform integrating genetic, Raman,
      photothermal, and photoacoustic methods. Using this approach, we discovered that
      multiwall carbon nanotubes induce previously unknown changes in gene expression
      in tomato leaves and roots, particularly, up-regulation of the stress-related
      genes, including those induced by pathogens and the water-channel LeAqp2 gene. A
      nano-bubble amplified photothermal/photoacoustic imaging, spectroscopy, and
      burning technique demonstrated the detection of multiwall carbon nanotubes in
      roots, leaves, and fruits down to the single nanoparticle and cell level. Thus,
      our integrated platform allows the study of nanoparticles' impact on plants with
      higher sensitivity and specificity, compared to existing assays.

PMID- 21189307
TI  - Suppressing effects of sunitinib on allergic rhinitis: previously undefined side
      effects with therapeutic potential.

PMID- 21189308
TI  - Effect of rosuvastatin on hemoglobin levels in patients with anemia and low-grade
      inflammation: a post hoc analysis of the JUPITER trial.

PMID- 21189309
TI  - Heart remodelling and obesity: the complexities and variation of cardiac
      geometry.

PMID- 21189310
TI  - New anticoagulant agents in acute coronary syndromes.

PMID- 21189311
TI  - Management of asymptomatic aortic stenosis.

PMID- 21189312
TI  - The patient with hypertrophic cardiomyopathy has a family.

PMID- 21189313
TI  - Propafenone contraindicated in the elderly?

PMID- 21189314
TI  - What is the best dose of aspirin in association with P2Y12 antagonists?

PMID- 21189315
TI  - The effect of acculturation on frailty among older Mexican Americans.
AB  - OBJECTIVE: To determine the effect of acculturation on becoming frail and
      prefrail over a 10-year period among older Mexican Americans. METHOD: A
      nationally representative sample of 2,049 Mexican Americans aged 67 to 108 was
      analyzed. Adjusted for sociodemographics and health, longitudinal multinomial
      mixed models examined the effects of English language and frequency of contact
      with Anglo-Americans on transitions among deceased, nonfrail, prefrail, and frail
      statuses. RESULTS: Greater English language proficiency was associated with a 10%
      reduced likelihood of becoming prefrail (p < .05) and marginally associated with
      a reduced likelihood of becoming frail (relative risk = 0.88; p = .07). Frequent
      contact with Anglos was significantly associated with a reduced likelihood of
      becoming frail (relative risk = 0.87; p < .05). DISCUSSION: Among older Mexican
      Americans, acculturation at baseline was protective of transitioning from a
      nonfrail or prefrail to a frail state. These findings suggest that increased
      acculturation may provide Mexican Americans with protection from health issues in
      old age.

PMID- 21189316
TI  - The distributional nexus of choroid plexus to cerebrospinal fluid, ependyma and
      brain: toxicologic/pathologic phenomena, periventricular destabilization, and
      lesion spread.
AB  - Bordering the ventricular cerebrospinal fluid (CSF) are epithelial cells of
      choroid plexus (CP), ependyma and circumventricular organs (CVOs) that contain
      homeostatic transporters for mediating secretion/reabsorption. The distributional
      pathway ("nexus") of CP-CSF-ependyma-brain furnishes peptides, hormones, and
      micronutrients to periventricular regions. In disease/toxicity, this nexus
      becomes a conduit for infectious and xenobiotic agents. The sleeping sickness
      trypanosome (a protozoan) disrupts CP and downstream CSF-brain. Piperamide is
      anti-trypanosomic but distorts CP epithelial ultrastructure by engendering
      hydropic vacuoles; this reflects phospholipidosis and altered lysosomal
      metabolism. CP swelling by vacuolation may occlude CSF flow. Toxic drug tools
      delineate injuries to choroidal compartments: cyclophosphamide (vasculature),
      methylcellulose (interstitium), and piperazine (epithelium). Structurally
      perturbed CP allows solutes to penetrate the ventricles. There, CSF-borne
      pathogens and xenobiotics may permeate the ependyma to harm neurogenic stem cell
      niches. Amoscanate, an anti-helmintic, potently injures rodent ependyma.
      Ependymal/brain regions near CP are vulnerable to CSF-borne toxicants; this
      proximity factor links regional barrier breakdown to nearby periventricular
      pathology. Diverse diseases (e.g., African sleeping sickness, multiple sclerosis)
      take early root in choroidal, circumventricular, or perivascular loci.
      Toxicokinetics informs on pathogen, anti-parasitic agent, and auto-antibody
      distribution along the CSF nexus. CVOs are susceptible to plasma-borne
      toxicants/pathogens. Countering the physico-chemical and pathogenic insults to
      the homeostasis-mediating ventricle-bordering cells sustains brain health and
      fluid balance.

PMID- 21189317
TI  - Glia-induced reversible disruption of blood-brain barrier integrity and
      neuropathological response of the neurovascular unit.
AB  - The blood-brain barrier (BBB) is the regulated interface that mediates selective
      transcellular transport of nutrients and essential components from the blood into
      the brain parenchyma. Many neurodegenerative diseases including stroke, multiple
      sclerosis, rheumatoid arthritis, and AIDS dementia exhibit loss of BBB integrity.
      Despite the increasing body of evidence for the involvement of glia in
      maintaining the BBB, few studies have addressed glial/endothelial/extracellular
      matrix interactions. A chemically induced astrocyte lesion provides a noninvasive
      model to study reversible BBB dysfunction in vivo. Blood-brain barrier integrity
      was assessed with fluorescent dextran tracers (3-70 kDa) and magnetic resonance
      imaging, in parallel with confocal and electron microscopy imaging of the
      neurovascular unit. These studies demonstrated modified tight-junction protein
      expression with loss of vascular integrity. We propose that adherens junction
      proteins and extracellular matrix remodeling provide a temporary size-selective
      barrier, whereas astrocyte and microglia activation direct tight-junction
      proteins to paracellular domains and restore BBB integrity. Morphological
      comparisons were made with the area postrema, a circumventricular organ with a
      naturally porous BBB. Further studies into cellular mechanisms of
      glial/endothelial/extracellular matrix interactions may identify novel glial
      based therapeutic targets and innovate therapies for modulating diseases in which
      gliosis and raised levels of pro-inflammatory mediators are central components.

PMID- 21189318
TI  - Enteropathogenic and enterohemorrhagic Escherichia coli type III secretion
      effector EspV induces radical morphological changes in eukaryotic cells.
AB  - Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic Escherichia coli
      (EHEC) are important human pathogens that rely on translocation of type III
      secretion system (T3SS) effectors for subversion of signal transduction pathways
      and colonization of the mammalian gut mucosa. While a core set of effectors is
      conserved between EPEC and EHEC strains, a growing number of accessory effectors
      that were found at various frequencies in clinical and environmental isolates
      have been recently identified. Recent genome projects identified espV as a
      pseudogene in EHEC but a putative functional gene in EPEC strains E110019 and E22
      and the closely related mouse pathogen Citrobacter rodentium. The aim of this
      study was to determine the distribution of espV among clinical EPEC and EHEC
      strains and to investigate its function and role in pathogenesis. espV was found
      in 16% of the tested strains. While deletion of espV from C. rodentium did not
      affect colonization dynamics or fitness in mixed infections, expression of EspV
      in mammalian cells led to drastic morphological alterations, which were
      characterized by nuclear condensation, cell rounding, and formation of dendrite
      like projections. Expression of EspV in yeast resulted in a dramatic increase in
      cell size and irreversible growth arrest. Although the role of EspV in infection
      and its target host cell protein(s) require further investigation, the data point
      to a novel mechanism by which the T3SS subverts cell signaling.

PMID- 21189319
TI  - Differential microbicidal effects of human histone proteins H2A and H2B on
      Leishmania promastigotes and amastigotes.
AB  - Recent studies have shown that histone proteins can act as antimicrobial peptides
      in host defense against extracellular bacteria, fungi, and Leishmania
      promastigotes. In this study, we used human recombinant histone proteins to
      further study their leishmaniacidal effects and the underlying mechanisms. We
      found that the histones H2A and H2B (but not H1(0)) could directly and
      efficiently kill promastigotes of Leishmania amazonensis, L. major, L.
      braziliensis, and L. mexicana in a treatment dose-dependent manner. Scanning
      electron microscopy revealed surface disruption of histone-treated promastigotes.
      More importantly, the preexposure of promastigotes to histone proteins markedly
      decreased the infectivity of promastigotes to murine macrophages (Mphis) in
      vitro. However, axenic and lesion-derived amastigotes of L. amazonensis and L.
      mexicana were relatively resistant to histone treatment, which correlated with
      the low levels of intracellular H2A in treated amastigotes. To understand the
      mechanisms underlying these differential responses, we investigated the role of
      promastigote surface molecules in histone-mediated killing. Compared with the
      corresponding controls, transgenic L. amazonensis promastigotes expressing lower
      levels of surface gp63 proteins were more susceptible to histone H2A, while L.
      major and L. mexicana promastigotes with targeted deletion of the
      lipophosphoglycan 2 (lpg2) gene (but not the lpg1 gene) were more resistant to
      histone H2A. We discuss the influence of promastigote major surface molecules in
      the leishmaniacidal effect of histone proteins. This study provides new
      information on host innate immunity to different developmental stages of
      Leishmania parasites.

PMID- 21189320
TI  - Sialic acid transport contributes to pneumococcal colonization.
AB  - Streptococcus pneumoniae is a major cause of pneumonia and meningitis. Airway
      colonization is a necessary precursor to disease, but little is known about how
      the bacteria establish and maintain colonization. Carbohydrates are required as a
      carbon source for pneumococcal growth and, therefore, for colonization. Free
      carbohydrates are not readily available in the naso-oropharynx; however, N- and O
      linked glycans are common in the airway. Sialic acid is the most common terminal
      modification on N- and O-linked glycans and is likely encountered frequently by
      S. pneumoniae in the airway. Here we demonstrate that sialic acid supports
      pneumococcal growth when provided as a sole carbon source. Growth on sialic acid
      requires import into the bacterium. Three genetic regions have been proposed to
      encode pneumococcal sialic acid transporters: one sodium solute symporter and two
      ATP binding cassette (ABC) transporters. Data demonstrate that one of these,
      satABC, is required for transport of sialic acid. A satABC mutant displayed
      significantly reduced growth on both sialic acid and the human glycoprotein alpha
      1. The importance of satABC for growth on human glycoprotein suggests that sialic
      acid transport may be important in vivo. Indeed, the satABC mutant was
      significantly reduced in colonization of the murine upper respiratory tract. This
      work demonstrates that S. pneumoniae is able to use sialic acid as a sole carbon
      source and that utilization of sialic acid is likely important during
      pneumococcal colonization.

PMID- 21189321
TI  - Full virulence of Pseudomonas aeruginosa requires OprF.
AB  - OprF is a general outer membrane porin of Pseudomonas aeruginosa, a well-known
      human opportunistic pathogen associated with severe hospital-acquired sepsis and
      chronic lung infections of cystic fibrosis patients. A multiphenotypic approach,
      based on the comparative study of a wild-type strain of P. aeruginosa, its
      isogenic oprF mutant, and an oprF-complemented strain, showed that OprF is
      required for P. aeruginosa virulence. The absence of OprF results in impaired
      adhesion to animal cells, secretion of ExoT and ExoS toxins through the type III
      secretion system (T3SS), and production of the quorum-sensing-dependent virulence
      factors pyocyanin, elastase, lectin PA-1L, and exotoxin A. Accordingly, in the
      oprF mutant, production of the signal molecules N-(3-oxododecanoyl)-l-homoserine
      lactone and N-butanoyl-l-homoserine lactone was found to be reduced and delayed,
      respectively. Pseudomonas quinolone signal (PQS) production was decreased, while
      its precursor, 4-hydroxy-2-heptylquinoline (HHQ), accumulated in the cells. Taken
      together, these results show the involvement of OprF in P. aeruginosa virulence,
      at least partly through modulation of the quorum-sensing network. This is the
      first study showing a link between OprF, PQS synthesis, T3SS, and virulence
      factor production, providing novel insights into virulence expression.

PMID- 21189322
TI  - Identification of Anaplasma marginale outer membrane protein antigens conserved
      between A. marginale sensu stricto strains and the live A. marginale subsp.
      centrale vaccine.
AB  - Live vaccination with Anaplasma marginale subsp. centrale (synonym for Anaplasma
      centrale) induces protection against severe disease upon challenge with A.
      marginale sensu stricto strains. Despite over a century of field use, the targets
      of protective immunity remained unknown. Using a broad proteomic approach, we
      identified the proteins in a challenge sensu stricto strain that were bound by
      the relevant antibody isotype induced by live vaccination with Anaplasma
      marginale subsp. centrale. A core of 15 proteins was identified in vaccinated
      animals across multiple major histocompatibility complex (MHC) haplotypes. This
      core separated into two structural/functional classes: "housekeeping" proteins
      involved in replication and metabolism and outer membrane proteins (OMPs).
      Orthologous proteins of both classes were identified within the vaccine strain
      and among sensu stricto strains. In contrast to the broad conservation among
      strains in the sequences of the housekeeping proteins, there was significantly
      greater divergence in the OMPs and greater divergence in both OMP sequences and
      the encoding locus structure between the vaccine strain and the sensu stricto
      strains than among the sensu stricto strains. The OMPs bound by live vaccine
      induced antibody overlapped with OMPs that were immunogenic in animals vaccinated
      with inactivated vaccines and subsequently protected against bacteremia and
      disease. The identification of this core set of OMPs is consistent with the
      hypothesis that "subdominant" immunogens are required for vaccine-induced
      protection against A. marginale and provides clear direction for development of a
      safer, more effective vaccine.

PMID- 21189323
TI  - Iron content differs between Francisella tularensis subspecies tularensis and
      subspecies holarctica strains and correlates to their susceptibility to H(2)O(2)
      induced killing.
AB  - Francisella tularensis, the causative agent of tularemia, is one of the most
      infectious bacterial pathogens known and is classified as a category A select
      agent and a facultative intracellular bacterium. Why F. tularensis subsp.
      tularensis causes a more severe form of tularemia than F. tularensis subsp.
      holarctica does is not known. In this study, we have identified prominent
      phenotypic differences between the subspecies, since we found that F. tularensis
      subsp. tularensis strains contained less iron than F. tularensis subsp.
      holarctica strains. Moreover, strain SCHU S4 of F. tularensis subsp. tularensis
      was less susceptible than FSC200 and the live vaccine strain (LVS) of F.
      tularensis subsp. holarctica to H(2)O(2)-induced killing. The activity of the
      H(2)O(2)-degrading enzyme catalase was similar between the strains, whereas the
      iron content affected their susceptibility to H(2)O(2), since iron starvation
      rendered F. tularensis subsp. holarctica strains more resistant to H(2)O(2).
      Complementing LVS with fupA, which encodes an important virulence factor that
      regulates iron uptake, reduced its iron content and increased the resistance to
      H(2)O(2)-mediated killing. By real-time PCR, it was demonstrated that FSC200 and
      LVS expressed higher levels of gene transcripts related to iron uptake and
      storage than SCHU S4 did, and this likely explained their high iron content.
      Together, the results suggest that F. tularensis subsp. tularensis strains have
      restricted iron uptake and storage, which is beneficial for their resistance to
      H(2)O(2)-induced killing. This may be an important factor for the higher
      virulence of this subspecies of F. tularensis, as reactive oxygen species, such
      as H(2)O(2), are important bactericidal components during tularemia.

PMID- 21189324
TI  - Strain-transcending Fc-dependent killing of Plasmodium falciparum by merozoite
      surface protein 2 allele-specific human antibodies.
AB  - It is widely accepted that antibody responses against the human parasitic
      pathogen Plasmodium falciparum protect the host from the rigors of severe malaria
      and death. However, there is a continuing need for the development of in vitro
      correlate assays of immune protection. To this end, the capacity of human
      monoclonal and polyclonal antibodies in eliciting phagocytosis and parasite
      growth inhibition via Fcgamma receptor-dependent mechanisms was explored. In
      examining the extent to which sequence diversity in merozoite surface protein 2
      (MSP2) results in the evasion of antibody responses, an unexpectedly high level
      of heterologous function was measured for allele-specific human antibodies. The
      dependence on Fcgamma receptors for opsonic phagocytosis and monocyte-mediated
      antibody-dependent parasite inhibition was demonstrated by the mutation of the Fc
      domain of monoclonal antibodies against both MSP2 and a novel vaccine candidate,
      peptide 27 from the gene PFF0165c. The described flow cytometry-based functional
      assays are expected to be useful for assessing immunity in naturally infected and
      vaccinated individuals and for prioritizing among blood-stage antigens for
      inclusion in blood-stage vaccines.

PMID- 21189325
TI  - Essential role for the major autolysin in the fibronectin-binding protein
      mediated Staphylococcus aureus biofilm phenotype.
AB  - Staphylococcus aureus clinical isolates are capable of producing at least two
      distinct types of biofilm mediated by the fibronectin-binding proteins (FnBPs) or
      the icaADBC-encoded polysaccharide intercellular adhesin (PIA). Deletion of the
      major autolysin gene atl reduced primary attachment rates and impaired FnBP
      dependent biofilm production on hydrophilic polystyrene in 12 clinical
      methicillin-resistant S. aureus (MRSA) isolates but had no effect on PIA
      dependent biofilm production by 9 methicillin-susceptible S. aureus (MSSA)
      isolates. In contrast, Atl was required for both FnBP- and PIA-mediated biofilm
      development on hydrophobic polystyrene. Here we investigated the role of Atl in
      biofilm production on hydrophilic polystyrene. The alternative sigma factor
      sigma(B), which represses RNAIII expression and extracellular protease
      production, was required for FnBP- but not PIA-dependent biofilm development.
      Furthermore, mutation of the agr locus enhanced FnBP-dependent biofilm
      development, whereas a sarA mutation, which increases protease production,
      blocked FnBP-mediated biofilm development. Mutation of sigB in MRSA isolate BH1CC
      lowered primary attachment rates, in part via reduced atl transcription.
      Posttranslational activation or inhibition of Atl activity with
      phenylmethylsulfonyl fluoride and polyanethole sodium sulfonate or mutation of
      the Atl amidase active site interfered with lytic activity and biofilm
      development. Consistent with these observations, extracellular DNA was important
      for the early stages of Atl/FnBP-dependent biofilm development. Further analysis
      of atl regulation revealed that atlR encodes a transcriptional repressor of the
      major autolysin and that an atlR::Tc(r) mutation in BH1CC enhanced biofilm
      forming capacity. These data reveal an essential role for the major autolysin in
      the early events of the FnBP-dependent S. aureus biofilm phenotype.

PMID- 21189327
TI  - MicroRNAs miR-199a-5p and -3p target the Brm subunit of SWI/SNF to generate a
      double-negative feedback loop in a variety of human cancers.
AB  - The chromatin remodeling complex SWI/SNF is an important epigenetic regulator
      that includes one Brm or BRG1 molecule as catalytic subunit. Brm and BRG1 do not
      function identically, so this complex can regulate gene expression either
      positively or negatively, depending on the promoter to which it is recruited.
      Notably, Brm attenuation due to posttranscription suppression occurs often in
      human tumor cells, in which this event contributes to their oncogenic potential.
      Here, we report that the 3'-untranslated region of Brm mRNA has two sites that
      are efficiently targeted by the microRNAs miR-199a-5p and -3p, revealing a novel
      mechanism for modulation of Brm-type SWI/SNF activity. Computational mapping of
      the putative promoter region of miR-199a-2 (miPPR-199a-2) has defined it as the
      major contributing genetic locus for miR-199a-5p and-3p production in these tumor
      cell lines. We validated this predicted region by direct promoter analysis to
      confirm that Egr1 is a strong positive regulator of the miR-199a-2 gene.
      Importantly, we also showed that Egr1, miR-199a-5p, and miR-199a-3p are expressed
      at high levels in Brm-deficient tumor cell lines but only marginally in Brm
      expressing tumor cells. Finally, we also obtained evidence that Brm negatively
      regulates Egr1. Together, our results reveal that miR-199a and Brm form a double
      negative feedback loop through Egr1, leading to the generation of these two
      distinct cell types during carcinogenesis. This mechanism may offer a partial
      explanation for why miR-199a-5p and -3p have been reported to be either
      upregulated or downregulated in a variety of tumors.

PMID- 21189326
TI  - TGF-beta promotion of Gli2-induced expression of parathyroid hormone-related
      protein, an important osteolytic factor in bone metastasis, is independent of
      canonical Hedgehog signaling.
AB  - Breast cancer frequently metastasizes to bone, in which tumor cells receive
      signals from the bone marrow microenvironment. One relevant factor is TGF-beta,
      which upregulates expression of the Hedgehog (Hh) signaling molecule, Gli2, which
      in turn increases secretion of important osteolytic factors such as parathyroid
      hormone-related protein (PTHrP). PTHrP inhibition can prevent tumor-induced bone
      destruction, whereas Gli2 overexpression in tumor cells can promote osteolysis.
      In this study, we tested the hypothesis that Hh inhibition in bone metastatic
      breast cancer would decrease PTHrP expression and therefore osteolytic bone
      destruction. However, when mice engrafted with human MDA-MB-231 breast cancer
      cells were treated with the Hh receptor antagonist cyclopamine, we observed no
      effect on tumor burden or bone destruction. In vitro analyses revealed that
      osteolytic tumor cells lack expression of the Hh receptor, Smoothened, suggesting
      an Hh-independent mechanism of Gli2 regulation. Blocking Gli signaling in
      metastatic breast cancer cells with a Gli2-repressor gene (Gli2-rep) reduced
      endogenous and TGF-beta-stimulated PTHrP mRNA expression, but did not alter tumor
      cell proliferation. Furthermore, mice inoculated with Gli2-Rep-expressing cells
      exhibited a decrease in osteolysis, suggesting that Gli2 inhibition may block TGF
      beta propagation of a vicious osteolytic cycle in this MDA-MB-231 model of bone
      metastasis. Accordingly, in the absence of TGF-beta signaling, Gli2 expression
      was downregulated in cells, whereas enforced overexpression of Gli2 restored
      PTHrP activity. Taken together, our findings suggest that Gli2 is required for
      TGF-beta to stimulate PTHrP expression and that blocking Hh-independent Gli2
      activity will inhibit tumor-induced bone destruction.

PMID- 21189328
TI  - Disruption of a Sirt1-dependent autophagy checkpoint in the prostate results in
      prostatic intraepithelial neoplasia lesion formation.
AB  - The Sirtuin family of proteins (SIRT) encode a group of evolutionarily conserved,
      NAD-dependent histone deacetylases, involved in many biological pathways. SIRT1,
      the human homologue of the yeast Silent Information Regulator 2 (Sir2) gene,
      deacetylates histones, p300, p53, and the androgen receptor. Autophagy is
      required for the degradation of damaged organelles and long-lived proteins, as
      well as for the development of glands such as the breast and prostate. Herein,
      homozygous deletion of the Sirt1 gene in mice resulted in prostatic
      intraepithelial neoplasia (PIN) associated with reduced autophagy. Genome-wide
      gene expression analysis of Sirt1(-/-) prostates demonstrated that endogenous
      Sirt1 repressed androgen responsive gene expression and induced autophagy in the
      prostate. Sirt1 induction of autophagy occurred at the level of autophagosome
      maturation and completion in cultured prostate cancer cells. These studies
      provide novel evidence for a checkpoint function of Sirt1 in the development of
      PIN and further highlight a role for SIRT1 as a tumor suppressor in the prostate.

PMID- 21189329
TI  - Reduced SMAD7 leads to overactivation of TGF-beta signaling in MDS that can be
      reversed by a specific inhibitor of TGF-beta receptor I kinase.
AB  - Even though myelodysplastic syndromes (MDS) are characterized by ineffective
      hematopoiesis, the molecular alterations that lead to marrow failure have not
      been well elucidated. We have previously shown that the myelosuppressive TGF-beta
      pathway is constitutively activated in MDS progenitors. Because there is
      conflicting data about upregulation of extracellular TGF-beta levels in MDS, we
      wanted to determine the molecular basis of TGF-beta pathway overactivation and
      consequent hematopoietic suppression in this disease. We observed that SMAD7, a
      negative regulator of TGF-beta receptor I (TBRI) kinase, is markedly decreased in
      a large meta-analysis of gene expression studies from MDS marrow-derived CD34(+)
      cells. SMAD7 protein was also found to be significantly decreased in MDS marrow
      progenitors when examined immunohistochemically in a bone marrow tissue
      microarray. Reduced expression of SMAD7 in hematopoietic cells led to increased
      TGF-beta-mediated gene transcription and enhanced sensitivity to TGF-beta
      mediated suppressive effects. The increased TGF-beta signaling due to SMAD7
      reduction could be effectively inhibited by a novel clinically relevant TBRI
      (ALK5 kinase) inhibitor, LY-2157299. LY-2157299 could inhibit TGF-beta-mediated
      SMAD2 activation and hematopoietic suppression in primary hematopoietic stem
      cells. Furthermore, in vivo administration of LY-2157299 ameliorated anemia in a
      TGF-beta overexpressing transgenic mouse model of bone marrow failure. Most
      importantly, treatment with LY-2157199 stimulated hematopoiesis from primary MDS
      bone marrow specimens. These studies demonstrate that reduction in SMAD7 is a
      novel molecular alteration in MDS that leads to ineffective hematopoiesis by
      activating of TGF-beta signaling in hematopoietic cells. These studies also
      illustrate the therapeutic potential of TBRI inhibitors in MDS.

PMID- 21189331
TI  - The intestine as an important contributor to prasugrel active metabolite
      formation in vivo.
AB  - Prasugrel [2-acetoxy-5-(alpha-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7
      tetrahydrothieno[3,2-c]pyridine], a thienopyridine antiplatelet agent, undergoes
      rapid hydrolysis in vivo to a thiolactone intermediate, 2-[2-oxo-6,7
      dihydrothieno[3,2-c]pyridin-5(4H)-yl]-1-cyclopropyl-2-(2-fluorophenyl)ethanone (R
      95913), which is further converted to a pharmacologically active metabolite, 2-[1
      2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-mercapto-3-piperidinylidene acetic
      acid (R-138727), by oxidation via cytochromes P450. In this study, we
      investigated how much the intestine and liver contribute to the formation of R
      95913 and R-138727 after intraduodenal administration of prasugrel (1 mg/kg) to
      portal vein- and hepatic vein-cannulated dogs. The areas under the plasma
      concentration-time curve up to 2 h of R-95913 in the portal, hepatic, and
      systemic veins were 525, 32, and 17 ng . h/ml, respectively, and those of R
      138727 were 564, 529, and 495 ng . h/ml, respectively. The dose of prasugrel was
      absorbed and then converted to R-95913 and R-138727 by 93 and 13%, respectively,
      in the intestine. In the liver, 23% of the R-95913, which passed through the
      intestine, was converted to R-138727. In conclusion, this is the first report to
      directly demonstrate that the conversion of prasugrel to R-138727 in the
      intestine is comparable to that converted in the liver of dogs.

PMID- 21189330
TI  - Metabolic pathways of the camptothecin analog AR-67.
AB  - 7-tert-Butyldimethylsilyl-10-hydroxycamptothecin (AR-67; also known as DB-67) is
      a novel lipophilic camptothecin analog in early-phase anticancer clinical trials.
      In support of these studies, we evaluated the metabolism of AR-67 in vitro and
      identified potential metabolites in patient samples. The lactone form of AR-67
      was found to be preferentially metabolized over AR-67 carboxylate in human
      microsomes. Subsequently, the lactone form was tested as a substrate in a panel
      of CYP450 and UDP-glucuronosyltransferase (UGT) enzymes known to metabolize the
      majority of clinically approved molecules. AR-67 was metabolized by CYP3A5,
      CYP3A4, CYP1A1, and CYP1A2, in order of activity. Extrahepatic UGT1A8 and UGT1A7
      possessed at least 6-fold higher metabolizing activity than UGT1A1 and other UGT
      enzymes tested. CYP1A1 and UGT1A7 displayed Michaelis-Menten kinetics, whereas
      CYP3A4, CYP3A5, and UGT1A8 displayed kinetics consistent with substrate
      inhibition. Chromatographic analysis of representative patient plasma and urine
      samples demonstrated the presence of AR-67 glucuronides and oxidized products in
      the urine but only in very minimal amounts. We conclude that limited in vivo
      metabolism of AR-67 by UGT1A1 may partly explain the absence of AR-67
      glucuronides in plasma and hypothesize that UGT1A8- and CYP3A-mediated
      biotransformation within the gastrointestinal epithelium may provide protective
      mechanisms against AR-67 gastrointestinal toxicity.

PMID- 21189332
TI  - CYP2G2, pseudogenized in human, is expressed in nasal mucosa of cynomolgus monkey
      and encodes a functional drug-metabolizing enzyme.
AB  - CYP2G2P is pseudogenized in humans because of two nonsense mutations (c.76C>T in
      exon 1 and c.382C>T in exon 3) in the putative coding region of the gene
      sequence, whereas mouse, rat, and rabbit CYP2Gs are expressed and functional in
      nasal mucosa. In this study, we assessed the intactness of CYP2G in a cynomolgus
      monkey, a macaque species important for drug metabolism studies because of its
      evolutionary closeness to human. On the basis of a gene sequence (highly
      identical to human CYP2G2P) found in the macaque genome, CYP2G2 cDNA was
      successfully isolated from cynomolgus monkey nasal mucosa. CYP2G2 cDNA,
      containing an open reading frame of 494 amino acids, was shown to share high
      sequence identity (nearly 95%) with the putative coding region of human CYP2G2P.
      Cynomolgus monkey CYP2G2 shared the highest sequence identity (59-61%) with
      CYP2A23, CYP2A24, and CYP2A26 among cynomolgus monkey cytochromes P450.
      Cynomolgus monkey CYP2G2 mRNA was predominantly expressed in the nasal mucosa,
      where CYP2G2 protein expression was also detected. Metabolic assays indicated
      that cynomolgus monkey CYP2G2 metabolized coumarin, similar to cynomolgus monkey
      CYP2A23, CYP2A24, and CYP2A26. Moreover, among 39 cynomolgus monkeys and 11
      rhesus monkeys examined in this study, only 2 cynomolgus monkeys and 1 rhesus
      monkey were heterozygous for c.76C>T. No animals carried c.382C>T. These results
      suggest that cynomolgus monkey CYP2G2 is a functional drug-metabolizing enzyme in
      nasal mucosa.

PMID- 21189333
TI  - Disorganizing experiences in second- and third-generation holocaust survivors.
AB  - Second-generation Holocaust survivors might not show direct symptoms of
      posttraumatic stress disorder or attachment disorganization, but are at risk for
      developing high levels of psychological distress. We present themes of difficult
      experiences of second-generation Holocaust survivors, arguing that some of these
      aversive experiences might have disorganizing qualities even though they do not
      qualify as traumatic. Based on in-depth interviews with 196 second-generation
      parents and their adolescent children, three themes of disorganizing experiences
      carried across generations were identified: focus on survival issues, lack of
      emotional resources, and coercion to please the parents and satisfy their needs.
      These themes reflect the frustration of three basic needs: competence,
      relatedness, and autonomy, and this frustration becomes disorganizing when it
      involves stability, potency, incomprehensibility, and helplessness. The findings
      shed light on the effect of trauma over the generations and, as such, equip
      therapists with a greater understanding of the mechanisms involved.

PMID- 21189336
TI  - Cerebral volumetric analysis over time in children with malformations of cortical
      development: a quantitative investigation.
AB  - Malformations of cortical development are common neurological disorders
      characterized by disruptions in the normal development of cerebral gray and white
      matter during fetal life. We performed a quantitative, partly longitudinal
      investigation of cerebral volumes in a cohort of children with cortical
      malformations to investigate how their anatomical abnormalities change over time.
      Cortical malformation subjects showed volumetric curves that were comparable with
      those reported for healthy individuals, and reached peak cerebral volume, gray
      matter volume, and white matter volume at ages similar to those reported for
      healthy children. Volumes of heterotopic gray matter, however, demonstrated
      increases that were out of proportion to changes in cortical volume or caudate
      nucleus volume, suggesting that misplaced gray matter can have a unique pattern
      of maturation. Our findings demonstrate that overall brain growth in children
      with cortical malformations appears to mirror that of the healthy population,
      although malformed regions can show distinct growth patterns.

PMID- 21189337
TI  - Posaconazole serum concentrations among cardiothoracic transplant recipients:
      factors impacting trough levels and correlation with clinical response to
      therapy.
AB  - Fifty-six serum posaconazole trough levels were measured in 17 cardiothoracic
      transplant recipients. Initial levels were <= 0.5, 0.51 to 0.99, and >= 1 MUg/ml
      for 47, 29, and 24% of patients, respectively. Median trough levels associated
      with therapeutic success were higher than those associated with failure (1.55
      versus 0.34 MUg/ml; P = 0.006). Patients with levels consistently >0.5 MUg/ml
      were more likely to have successful outcome (P = 0.055). Age >= 65 years, oral
      administration, and absence of proton pump inhibitors were associated with higher
      levels of posaconazole (P = 0.006, 0.006, and 0.001, respectively).

PMID- 21189338
TI  - Antimicrobial susceptibility of clinically relevant Gram-positive anaerobic cocci
      collected over a three-year period in the Netherlands.
AB  - The susceptibility of 14 species of 115 Gram-positive anaerobic cocci (GPAC) was
      determined for 14 antibiotics. To assure correct identification, strains were
      genotypically identified by fluorescence in situ hybridization and sequencing.
      Susceptibility differences (MIC50 and MIC90) for penicillin G, clindamycin,
      tigecycline, levofloxacin, amoxicillin-clavulanic acid, cefoxitin, ertapenem,
      meropenem, metronidazole, and doxycycline were found for the three clinically
      most relevant GPAC species: Finegoldia magna, Parvimonas micra, and Peptoniphilus
      harei.

PMID- 21189339
TI  - Interaction potential of etravirine with drug transporters assessed in vitro.
AB  - Etravirine is a novel nonnucleoside reverse transcriptase inhibitor (NNRTI) for
      the treatment of HIV-1 infections. ABC transporters potentially mediate
      clinically relevant drug-drug interactions. We assessed substrate characteristics
      and the inhibitory and inductive potential of etravirine on ABC transporters.
      Etravirine did not inhibit P-gp/ABCB1 and was not transported by the tested ABC
      transporters but was a potent inhibitor of BCRP/ABCG2. Etravirine induced several
      ABC transporters, especially BCRP/ABCG2. These data demonstrate that etravirine
      has the potential for drug-drug interactions by modulation of expression and
      function of several ABC transporters.

PMID- 21189340
TI  - Treatment with linezolid or vancomycin in combination with rifampin is effective
      in an animal model of methicillin-resistant Staphylococcus aureus foreign body
      osteomyelitis.
AB  - Rifampin monotherapy was compared to the combination of linezolid or vancomycin
      with rifampin in an experimental rat model of methicillin-resistant
      Staphylococcus aureus (MRSA) chronic foreign body osteomyelitis. MRSA was
      inoculated into the proximal tibia, and a titanium wire was implanted. Four weeks
      after infection, rats were treated intraperitoneally for 21 days with rifampin
      alone (n = 16), linezolid plus rifampin (n = 14), or vancomycin plus rifampin (n
      = 13). Thirteen animals received no treatment. At completion of treatment,
      qualitative cultures of the wire and quantitative cultures of the bone (reported
      as median values) were performed. Quantitative cultures from the control,
      rifampin monotherapy, linezolid-plus-rifampin, and vancomycin-plus-rifampin
      groups revealed 4.54, 0.71, 0.10, and 0.50 log10 CFU/gram of bone, respectively.
      The bacterial load was significantly reduced in all treatment groups compared to
      that in the control group. Rifampin resistance was detected in isolates from 10,
      2, and 1 animal in the rifampin, linezolid-plus-rifampin, and vancomycin-plus
      rifampin groups, respectively. Cultures of the removed wire revealed bacterial
      growth in 1 and 2 animals in the rifampin and linezolid-plus-rifampin groups,
      respectively, with no growth in the vancomycin-plus-rifampin group and growth
      from all wires in the untreated group. In conclusion, we demonstrated that
      combination treatment with linezolid plus rifampin or vancomycin plus rifampin is
      effective in an animal model of MRSA foreign body osteomyelitis in the context of
      retention of the infected foreign body.

PMID- 21189341
TI  - NDM-1-producing Escherichia coli in Germany.

PMID- 21189342
TI  - Genotypic resistance in Helicobacter pylori strains correlates with
      susceptibility test and treatment outcomes after levofloxacin- and clarithromycin
      based therapies.
AB  - The accuracy of genotypic resistance to levofloxacin (gyrA mutations) and its
      agreement with treatment outcomes after levofloxacin-based therapy have not been
      reported. We aimed to assess the correlation. Helicobacter pylori strains
      isolated from patients who received levofloxacin-based and clarithromycin-based
      triple therapies in a previous randomized trial were analyzed for point mutations
      in gyrA and 23S rRNA. PCR followed by direct sequencing was used to assess the
      gyrA and 23S rRNA mutations. An agar dilution test was used to determine the MICs
      of clarithromycin and levofloxacin. We found that the agreement between genotypic
      and phenotypic resistance to levofloxacin was best when the MIC breakpoint was >1
      MUg/ml (kappa coefficient, 0.754). The eradication rates in patients with and
      without gyrA mutations were 41.7% and 82.7%, respectively (P = 0.003). The
      agreement between genotypic and phenotypic resistance to clarithromycin was best
      when the MIC breakpoint was >2 MUg/ml (kappa, 0.694). The eradication rates in
      patients with and without 23S rRNA mutations were 7.7% and 93.5%, respectively (P
      < 0.001). The agreements (kappa coefficient) between therapeutic outcomes after
      clarithromycin-based triple therapy and genotypic and phenotypic resistance were
      0.671 and 0.356, respectively. The agreements (kappa coefficient) between
      therapeutic outcomes after levofloxacin-based triple therapy and genotypic and
      phenotypic resistance were 0.244 and 0.190, respectively. In conclusion, gyrA and
      23S rRNA mutations in H. pylori strains appeared to be better markers than
      phenotypic resistance in the prediction of treatment outcomes. The optimal
      breakpoints for levofloxacin and clarithromycin resistance appeared to be >1
      MUg/ml and >2 MUg/ml, respectively.

PMID- 21189343
TI  - In vitro activities of arylomycin natural-product antibiotics against
      Staphylococcus epidermidis and other coagulase-negative staphylococci.
AB  - The arylomycins are a class of natural-product antibiotics that act via the
      inhibition of type I signal peptidase (SPase), and we have found in diverse
      bacteria that their activity is limited by the presence of a resistance
      conferring Pro residue in SPase that reduces inhibitor binding. We have also
      demonstrated that Staphylococcus epidermidis, which lacks this Pro residue, is
      extremely susceptible to the arylomycins. Here, to further explore the potential
      utility of the arylomycins, we report an analysis of the activity of a synthetic
      arylomycin derivative, arylomycin C16, against clinical isolates of S.
      epidermidis and other coagulase-negative staphylococci (CoNS) from distinct
      geographical locations. Against many important species of CoNS, including S.
      epidermidis, S. haemolyticus, S. lugdunensis, and S. hominis, we find that
      arylomycin C16 exhibits activity equal to or greater than that of vancomycin, the
      antibiotic most commonly used to treat CoNS infections. While the susceptibility
      was generally correlated with the absence of the previously identified Pro
      residue, several cases were identified where additional factors also appear to
      contribute.

PMID- 21189344
TI  - The presence of leukocytes in ex vivo assays significantly increases the 50
      percent inhibitory concentrations of artesunate and chloroquine against
      Plasmodium vivax and Plasmodium falciparum.
AB  - Plasmodium species ex vivo sensitivity assay protocols differ in the requirement
      for leukocyte removal before culturing. This study shows that the presence of
      leukocytes significantly increases the 50% inhibitory concentration (IC50) of P.
      vivax and P. falciparum to artesunate and chloroquine relative to results with
      the paired leukocyte-free treatment. Although leukocyte removal is not an
      essential requirement for the conduct of ex vivo assays, its use has important
      implications for the interpretation of temporal and spatial antimalarial
      sensitivity data.

PMID- 21189345
TI  - Early dissemination of NDM-1- and OXA-181-producing Enterobacteriaceae in Indian
      hospitals: report from the SENTRY Antimicrobial Surveillance Program, 2006-2007.
AB  - Among 39 carbapenem-resistant Enterobacteriaceae (2.7% overall; Escherichia coli,
      Enterobacter cloacae, and Klebsiella pneumoniae strains) isolated in 2006 and
      2007 in India, 15 strains carried bla(NDM-1) and 10 harbored a gene encoding a
      variant of the carbapenemase OXA-48, named bla(OXA-181). One E. cloacae strain
      harbored bla(VIM-6), and one K. pneumoniae strain carrying bla(OXA-181) also
      possessed bla(VIM-5). Multiple pulsed-field gel electrophoresis patterns and
      clonal dissemination within and among sites were observed. Isolates producing NDM
      1 were disseminated in Indian health care facilities as early as 2006.

PMID- 21189346
TI  - Quantifying diffusion in a biofilm of Streptococcus mutans.
AB  - In biofilms, diffusion may limit the chemical activity of nutrients, toxic
      compounds, and medicines. This study provides direct, noninvasive insight into
      the factors that will most effectively limit the transport of antibiotics and
      biocides in biofilms. Self-diffusion coefficients have been determined for a
      number of fluorescent probes in biofilms of Streptococcus mutans using
      fluorescence correlation spectroscopy. The effects of probe size and charge and
      the roles of biofilm pH, ionic strength, and heterogeneity were studied
      systematically. The relative diffusion coefficients (D in the biofilm divided by
      that in water) decreased with increasing probe size (3,000-molecular-weight [3K],
      10K, 40K, 70K, and 2,000K dextrans). Studies using variably charged substrates
      (tetramethylrhodamine, Oregon Green, rhodamine B, and rhodamine 6G) showed that
      the self-diffusion coefficients decreased with an increasing negative charge of
      the fluorescent probes. No significant effect was observed for changes to the
      ionic strength (10-4 to 10-1 M) or pH (4 to 9) of the biofilm. Biofilm
      heterogeneity was responsible for variations of ca. one order of magnitude in the
      diffusion coefficients.

PMID- 21189347
TI  - In vitro activity of doripenem against Burkholderia cepacia complex isolates from
      non-cystic fibrosis patients.

PMID- 21189348
TI  - Mechanism of bactericidal activity of microcin L in Escherichia coli and
      Salmonella enterica.
AB  - For the first time, the mechanism of action of microcin L (MccL) was investigated
      in live bacteria. MccL is a gene-encoded peptide produced by Escherichia coli
      LR05 that exhibits a strong antibacterial activity against related
      Enterobacteriaceae, including Salmonella enterica serovars Typhimurium and
      Enteritidis. We first subcloned the MccL genetic system to remove the sequences
      not involved in MccL production. We then optimized the MccL purification
      procedure to obtain large amounts of purified microcin to investigate its
      antimicrobial and membrane properties. We showed that MccL did not induce outer
      membrane permeabilization, which indicated that MccL did not use this way to kill
      the sensitive cell or to enter into it. Using a set of E. coli and Salmonella
      enterica mutants lacking iron-siderophore receptors, we demonstrated that the
      MccL uptake required the outer membrane receptor Cir. Moreover, the MccL
      bactericidal activity was shown to depend on the TonB protein that transduces the
      proton-motive force of the cytoplasmic membrane to transport iron-siderophore
      complexes across the outer membrane. Using carbonyl cyanide 3
      chlorophenylhydrazone, which is known to fully dissipate the proton-motive force,
      we proved that the proton-motive force was required for the bactericidal activity
      of MccL on E. coli. In addition, we showed that a primary target of MccL could be
      the cytoplasmic membrane: a high level of MccL disrupted the inner membrane
      potential of E. coli cells. However, no permeabilization of the membrane was
      detected.

PMID- 21189349
TI  - Human beta-defensin 2 and beta-defensin 3 chimeric peptides reveal the structural
      basis of the pathogen specificity of their parent molecules.
AB  - Despite partial sequence identity and structural similarity, human beta-defensin
      3 (HBD3) kills Staphylococcus aureus with a 4- to 8-fold higher efficiency than
      human beta-defensin 2 (HBD2), whereas the activities against Escherichia coli are
      identical. The design and characterization of HBD2/HBD3 chimeric peptides
      revealed that distinct molecular regions are responsible for their divergent
      killing properties. Two of the chimeras killed both E. coli and S. aureus with an
      even higher efficacy than the wild-type molecules. Moreover, one of these two
      chimeras maintained its high killing activities in the presence of physiologic
      salt concentrations. Due to the broad spectrum of their antimicrobial activities
      against many human multidrug-resistant pathogens, these two designer peptides of
      human origin represent promising templates for a new class of antibiotics.

PMID- 21189350
TI  - Novel bacterial NAD+-dependent DNA ligase inhibitors with broad-spectrum activity
      and antibacterial efficacy in vivo.
AB  - DNA ligases are indispensable enzymes playing a critical role in DNA replication,
      recombination, and repair in all living organisms. Bacterial NAD+-dependent DNA
      ligase (LigA) was evaluated for its potential as a broad-spectrum antibacterial
      target. A novel class of substituted adenosine analogs was discovered by target
      based high-throughput screening (HTS), and these compounds were optimized to
      render them more effective and selective inhibitors of LigA. The adenosine
      analogs inhibited the LigA activities of Escherichia coli, Haemophilus
      influenzae, Mycoplasma pneumoniae, Streptococcus pneumoniae, and Staphylococcus
      aureus, with inhibitory activities in the nanomolar range. They were selective
      for bacterial NAD+-dependent DNA ligases, showing no inhibitory activity against
      ATP-dependent human DNA ligase 1 or bacteriophage T4 ligase. Enzyme kinetic
      measurements demonstrated that the compounds bind competitively with NAD+. X-ray
      crystallography demonstrated that the adenosine analogs bind in the AMP-binding
      pocket of the LigA adenylation domain. Antibacterial activity was observed
      against pathogenic Gram-positive and atypical bacteria, such as S. aureus, S.
      pneumoniae, Streptococcus pyogenes, and M. pneumoniae, as well as against Gram
      negative pathogens, such as H. influenzae and Moraxella catarrhalis. The mode of
      action was verified using recombinant strains with altered LigA expression, an
      Okazaki fragment accumulation assay, and the isolation of resistant strains with
      ligA mutations. In vivo efficacy was demonstrated in a murine S. aureus thigh
      infection model and a murine S. pneumoniae lung infection model. Treatment with
      the adenosine analogs reduced the bacterial burden (expressed in CFU) in the
      corresponding infected organ tissue as much as 1,000-fold, thus validating LigA
      as a target for antibacterial therapy.

PMID- 21189351
TI  - Hot spots of integrase genotypic changes leading to HIV-2 resistance to
      raltegravir.
AB  - We studied seven heavily pretreated HIV-2-infected patients exhibiting a
      virological failure while receiving a salvage raltegravir-containing regimen. At
      the time of virological failure, different resistance genetic pathways were
      observed: T97A-Y143C, Q148K, Q148R, G140S-Q148R, E92Q-Y143R-N155H, and T97A
      N155H. Thus, despite a 40% difference in integrase genes between HIV-1 and HIV-2,
      the genetic pathways leading to raltegravir resistance are similar.

PMID- 21189352
TI  - Prepared for anything?: an investigation of female genital arousal in response to
      rape cues.
AB  - Men's genital arousal occurs in response to a limited number of sexual stimuli,
      whereas women's genital arousal occurs in response to a wide range of sexual
      stimuli, including those depicting nonpreferred cues. Researchers have
      hypothesized that women's nonspecific pattern of genital arousal prepares the
      body for sexual activity, thus functioning to protect the genital organs against
      injury. If this hypothesis is correct, women should show genital responses to any
      cues suggesting sexual activity, even unappealing cues that involve nonconsensual
      sex and extreme violence. Fifteen men and 15 women listened to fourteen 2-min
      audiotaped narratives that depicted an interaction between a man and a woman and
      that varied factorially according to the presence of consent, violence, and
      sexual activity. The results support the preparation hypothesis: Men showed the
      greatest genital arousal in response to narratives depicting consensual,
      nonviolent sex, whereas women showed similar responses to all the narratives
      involving sexual activities, including those describing a sexual assault.

PMID- 21189354
TI  - Evidence for a sensitive period for acculturation: younger immigrants report
      acculturating at a faster rate.
AB  - Though recent adult immigrants often seem less acculturated to their new society
      than people who immigrated as children, it is not clear whether this difference
      is driven by duration of exposure or exposure during a sensitive developmental
      period. In a study aimed at disambiguating these influences, community and
      student samples of Hong Kong immigrants to Vancouver, Canada, completed the
      Vancouver Index of Acculturation, a measure that assesses respondents'
      identification with their mainstream and heritage cultures. A longer duration of
      exposure was found to be associated with greater identification with Canadian
      culture only at younger ages of immigration, but not at later ages of
      immigration. Conversely, identification with Chinese culture was unaffected by
      either age of immigration or length of exposure to Canadian culture. These
      findings provide evidence for a sensitive period for acculturation: People are
      better able to identify with a host culture the longer their exposure to it, but
      only if this exposure occurs when they are relatively young.

PMID- 21189353
TI  - Tracking without perceiving: a dissociation between eye movements and motion
      perception.
AB  - Can people react to objects in their visual field that they do not consciously
      perceive? We investigated how visual perception and motor action respond to
      moving objects whose visibility is reduced, and we found a dissociation between
      motion processing for perception and for action. We compared motion perception
      and eye movements evoked by two orthogonally drifting gratings, each presented
      separately to a different eye. The strength of each monocular grating was
      manipulated by inducing adaptation to one grating prior to the presentation of
      both gratings. Reflexive eye movements tracked the vector average of both
      gratings (pattern motion) even though perceptual responses followed one motion
      direction exclusively (component motion). Observers almost never perceived
      pattern motion. This dissociation implies the existence of visual-motion signals
      that guide eye movements in the absence of a corresponding conscious percept.

PMID- 21189355
TI  - Isokinetic strength, endurance, and subjective outcomes after biceps tenotomy
      versus tenodesis: a postoperative study.
AB  - BACKGROUND: Similar subjective outcomes have been reported for tenotomy or
      tenodesis of the long head of the biceps. Few studies have reported on
      postoperative strength and endurance. HYPOTHESIS: Biceps tenodesis results in
      superior subjective outcomes, strength, and endurance compared with tenotomy.
      STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Participants completed
      isokinetic strength and endurance testing for elbow flexion and supination on the
      operative and nonoperative sides a minimum of 2 years after biceps tenotomy or
      tenodesis. Modified American Shoulder and Elbow Surgeons (MASES) and Single
      Assessment Numeric Evaluation (SANE) scores were obtained. The
      operative/nonoperative strength and endurance scores were compared for the
      tenotomy and tenodesis groups, with the nonoperative shoulder serving as the
      control for each participant's operative shoulder. Change scores for strength and
      endurance were reported as percentage increase or decrease as compared with the
      nonoperative side. Change scores and MASES and SANE scores were compared between
      the 2 groups. The presence of a "popeye" deformity or pain at the tenodesis site
      was noted. RESULTS: Thirty-five patients (19 tenotomy, 16 tenodesis) were
      studied. No significant difference was noted in postoperative MASES and SANE
      scores. Operative-side peak supination torque was significantly decreased
      relative to the nonoperative side in the tenotomy group, which had a
      significantly larger decrease in supination peak torque than did the tenodesis
      group on comparison of change scores. No significant difference was noted for
      peak flexion torque or flexion/supination endurance between operative and
      nonoperative sides in either group or between change scores for peak flexion
      torque or flexion/supination endurance in the tenotomy and tenodesis groups. Four
      tenotomy patients had a popeye deformity, 2 of whom reported painful cramping.
      Two patients had pain at the tenodesis site. CONCLUSION: Subjective outcomes are
      similar for patients treated with tenotomy and tenodesis. Tenotomy decreases
      supination peak torque relative to the nonoperative side and tenodesis.

PMID- 21189356
TI  - Functional recovery of the donor knee after autologous osteochondral
      transplantation for capitellar osteochondritis dissecans.
AB  - BACKGROUND: Osteochondral autograft transplantation has been advocated to treat
      severe osteochondritis dissecans of the humeral capitellum in throwing athletes
      to reproduce the normal hyaline cartilage and achieve long-term elbow function.
      Although some authors have reported good outcomes, the current authors are
      concerned about functional recovery of the donor knee after osteochondral grafts
      have been harvested. PURPOSE: The present prospective study analyzed functional
      recovery of the donor knee after osteochondral graft harvest. STUDY DESIGN: Case
      series; Level of evidence, 4. METHODS: Twelve male patients (average age at
      surgery, 14.4 years) had severe osteochondritis dissecans of the humeral
      capitellum treated with osteochondral autograft transplantation from the
      contralateral knee joint. The donor knee of each patient was assessed for pain
      (visual analog scale), joint effusion, Lysholm score, radiographic findings, and
      muscle strength (60 and 180 deg/sec). RESULTS: At 3 months after surgery, 10
      patients were pain-free (visual analog scale score, 0); none had knee joint
      effusion; and 10 gained 100 points in the Lysholm score. However, muscle power
      (60 deg/sec) of the knee extensor revealed 8 patients with reduced muscle
      strength at 3 months compared with the preoperative level, although 11 patients
      reached preoperative knee extensor muscle strength at 12 months. Radiographic
      findings at 24 months showed that none of the patients had knee osteoarthritis.
      CONCLUSION: A time lag was evident in recovery between postoperative symptoms and
      muscle power at 3 months. However, harvesting osteochondral grafts did not exert
      adverse effects on donor knee function in young athletes at 2 years after
      undergoing osteochondral autograft transplantation for capitellar osteochondritis
      dissecans.

PMID- 21189357
TI  - Open repair of isolated traumatic subscapularis tendon tears.
AB  - BACKGROUND: Diagnosis, operative treatment, and outcome assessment of isolated
      traumatic subscapularis tendon tears have not been widely studied. PURPOSE: To
      report the clinical outcome, value of clinical tests, predictive outcome factors,
      and return to sports in the management of isolated traumatic subscapularis tendon
      tears. STUDY DESIGN: Case series; level of evidence, 4. METHODS: Thirty
      consecutive patients with a confirmed isolated subscapularis tear, except for
      associated biceps tendon injury or humeral avulsion of the glenohumeral ligaments
      (HAGL) lesions, found at arthroscopy were included in the study. The average age
      of the study population was 43.1 years. In all 30 patients, a traumatic event
      caused the onset of symptoms. The mean delay between trauma and surgery was 4
      months. All patients underwent open tendon reconstruction with a suture anchor
      technique via a deltopectoral approach. Clinical assessment was done using the
      Constant score and specific subscapularis tests. Postoperative tendon integrity
      was assessed with ultrasound and magnetic resonance imaging. Sports activity,
      including competition level, sports discipline, and postoperative return to
      sports, was evaluated. RESULTS: The average duration of follow-up was 46 months
      (range, 25-72 months). Seven patients had a full-thickness tear of the upper
      third of the tendon, 11 patients a full-thickness tear of the upper two-thirds of
      the tendon, and 12 patients had a complete subscapularis tendon tear. The
      Constant score increased from 51.3 preoperatively to 82.2 postoperatively (P <
      .01). Twenty-seven patients rated their postoperative result as excellent or
      good. Most positive preoperative lift-off and belly-press tests were reversed by
      surgery, with a rate of 6 (20%) persistent positive tests after surgery. Positive
      postoperative subscapularis tests were more likely related to a higher
      preoperative degree of fatty subscapularis muscle infiltration (P < .05).
      Ultrasound and magnetic resonance imaging revealed a structural intact repair at
      follow-up in 28 shoulders (93%). Seventy-five percent of athletes returned to
      their previous competition level. CONCLUSION: Early repair of isolated traumatic
      subscapularis tendon tears and associated biceps tendon lesions or HAGL lesions
      achieves good functional outcomes with a low re-rupture rate and allows return to
      sports activity. Delay of surgery and higher degrees of preoperative fatty
      infiltration of the subscapularis muscle impair postoperative subscapularis
      function.

PMID- 21189358
TI  - Pathways regulated by glucocorticoids in omental and subcutaneous human adipose
      tissues: a microarray study.
AB  - Glucocorticoids (GC) are powerful regulators of adipocyte differentiation,
      metabolism, and endocrine function and promote the development of upper body
      obesity, especially visceral fat stores. To provide a comprehensive understanding
      of how GC affect adipose tissue and adipocyte function, we analyzed patterns of
      gene expression (HG U95 Affymetrix arrays) after culture of abdominal
      subcutaneous (Abd sc) and omental (Om) adipose tissues from severely obese
      subjects (3 F, 1 M) in the presence of insulin or insulin (7 nM) plus
      dexamethasone (Dex, 25 nM) for 7 days. About 20% (561 genes in Om and 569 genes
      in sc) of 2,803 adipose expressed genes were affected by long-term GC. While most
      of the genes (90%) were commonly regulated by Dex in both depots, 26 in Om and 34
      in Abd sc were affected by Dex in only one depot. 60% of the commonly upregulated
      genes were involved in metabolic pathways and were expressed mainly in
      adipocytes. Dex suppressed genes in immune/inflammatory (IL-6, IL-8, and MCP-1,
      expressed in nonadipocytes) and proapoptotic pathways, yet induced genes related
      to the acute-phase response (SAA, factor D, haptoglobin, and RBP4, expressed in
      adipocytes) and stress/defense response. Functional classification analysis
      showed that Dex also induced expression levels of 22 transcription factors
      related to insulin action and lipogenesis (LXRalpha, STAT5alpha, SREBP1, and
      FoxO1) and immunity/adipogenesis (TSC22D3) while suppressing 17 transcription
      factors in both depots. Overall, these studies reveal the powerful effects of GC
      on gene networks that regulate many key functions in human adipose tissue.

PMID- 21189359
TI  - Progesterone increases skeletal muscle mitochondrial H2O2 emission in
      nonmenopausal women.
AB  - The luteal phase of the female menstrual cycle is associated with both 1)
      elevated serum progesterone (P4) and estradiol (E2), and 2) reduced insulin
      sensitivity. Recently, we demonstrated a link between skeletal muscle
      mitochondrial H(2)O(2) emission (mE(H2O2)) and insulin resistance. To determine
      whether serum levels of P4 and/or E(2) are related to mitochondrial function,
      mE(H2O2) and respiratory O(2) flux (Jo(2)) were measured in permeabilized
      myofibers from insulin-sensitive (IS, n = 24) and -resistant (IR, n = 8)
      nonmenopausal women (IR = HOMA-IR > 3.6). Succinate-supported mE(H2O2) was more
      than 50% greater in the IR vs. IS women (P < 0.05). Interestingly, serum P4
      correlated positively with succinate-supported mE(H2O2) (r = 0. 53, P < 0.01). To
      determine whether P4 or E2 directly affect mitochondrial function, saponin
      permeabilized vastus lateralis myofibers biopsied from five nonmenopausal women
      in the early follicular phase were incubated in P4 (60 nM), E2 (1.4 nM), or both.
      P4 alone inhibited state 3 Jo(2), supported by multisubstrate combination (P <
      0.01). However, E2 alone or in combination with P4 had no effect on Jo(2). In
      contrast, during state 4 respiration, supported by succinate and
      glycerophosphate, mE(H2O2) was increased with P4 alone or in combination with E2
      (P < 0.01). The results suggest that 1) P4 increases mE(H2O2) with or without E2;
      2) P4 alone inhibits Jo(2) but not when E2 is present; and 3) P4 is related to
      the mE(H2O2) previously linked to skeletal muscle insulin resistance.

PMID- 21189361
TI  - Advantage of predictive modeling in tracer studies.

PMID- 21189360
TI  - In vivo activation of ROCK1 by insulin is impaired in skeletal muscle of humans
      with type 2 diabetes.
AB  - To determine whether serine/threonine ROCK1 is activated by insulin in vivo in
      humans and whether impaired activation of ROCK1 could play a role in the
      pathogenesis of insulin resistance, we measured the activity of ROCK1 and the
      protein content of the Rho family in vastus lateralis muscle of lean, obese
      nondiabetic, and obese type 2 diabetic subjects. Biopsies were taken after an
      overnight fast and after a 3-h hyperinsulinemic euglycemic clamp. Insulin
      stimulated GDR was reduced 38% in obese nondiabetic subjects compared with lean,
      62% in obese diabetic subjects compared with lean, and 39% in obese diabetic
      compared with obese nondiabetic subjects (all comparisons P < 0.001). Insulin
      stimulated IRS-1 tyrosine phosphorylation is impaired 41-48% in diabetic subjects
      compared with lean or obese subjects. Basal activity of ROCK1 was similar in all
      groups. Insulin increased ROCK1 activity 2.1-fold in lean and 1.7-fold in obese
      nondiabetic subjects in muscle. However, ROCK1 activity did not increase in
      response to insulin in muscle of obese type 2 diabetic subjects without change in
      ROCK1 protein levels. Importantly, insulin-stimulated ROCK1 activity was
      positively correlated with insulin-mediated GDR in lean subjects (P < 0.01) but
      not in obese or type 2 diabetic subjects. Moreover, RhoE GTPase that inhibits the
      catalytic activity of ROCK1 by binding to the kinase domain of the enzyme is
      notably increased in obese type 2 diabetic subjects, accounting for defective
      ROCK1 activity. Thus, these data suggest that ROCK1 may play an important role in
      the pathogenesis of resistance to insulin action on glucose disposal in muscle of
      obese type 2 diabetic subjects.

PMID- 21189363
TI  - A potential interaction between warfarin and atovaquone.
AB  - OBJECTIVE: To report a case of increased international normalized ratio (INR) in
      a patient established on warfarin therapy who was then initiated on atovaquone
      therapy. CASE SUMMARY: A 53-year-old African American male with HIV was
      prescribed warfarin 5 mg/day for 12 months after diagnosis of idiopathic deep
      vein thrombosis and bilateral pulmonary emboli (target INR 2.5 [range 2.0-3.0]).
      The patient required Pneumocystis jiroveci pneumonia prophylaxis and was
      prescribed atovaquone instead of trimethoprim/sulfamethoxazole therapy because of
      the latter drug's known interaction with warfarin. The patient's INR rose by
      greater than 50% (from 2.3 to 3.5) after 7 days of concomitant warfarin and
      atovaquone. In response, the patient's total weekly warfarin dose was decreased
      by 5%. Eight days later, the patient's INR was still supratherapeutic at 3.1.
      Approximately 4 weeks later, his INR was 4.2. One dose of warfarin was withheld
      and then the total weekly warfarin dosage was decreased by another 10%. Eight
      days later, the patient discontinued atovaquone therapy but continued on warfarin
      as prescribed. One day after atovaquone discontinuation, his INR decreased to
      1.7. Due to this subtherapeutic INR level, 8 days later the total weekly warfarin
      dose was increased by 5%. Although a follow-up appointment was scheduled, no
      further INR values were obtained because the patient's 12-month course of
      anticoagulation therapy was completed and warfarin was discontinued. The patient
      did not report any adverse effects or signs or symptoms of hemorrhage while his
      INR values were supratherapeutic. DISCUSSION: Warfarin's potential for
      interactions with other highly protein-bound drugs, such as atovaquone, can
      result in displacement from protein binding sites and increased serum
      concentrations of warfarin. Based on a search of MEDLINE/PubMed, International
      Pharmaceutical Abstracts, and the Food and Drug Administration MedWatch Adverse
      Event Reporting Program (all through July 31, 2010), no cases were found of an
      interaction between atovaquone and warfarin. The Horn Drug Interaction
      Probability Scale calculated this to be a probable interaction between warfarin
      and atovaquone. CONCLUSIONS: Although current medication references do not report
      an interaction between atovaquone and warfarin, knowledge of their
      pharmacodynamic properties can enable practitioners to anticipate the
      consequences of a possible transient increase in warfarin serum concentration,
      such as that seen in our patient, when given concomitantly.

PMID- 21189364
TI  - Autoimmune hemolytic anemia following MF59-adjuvanted influenza vaccine
      administration: a report of two cases.
AB  - OBJECTIVE: To describe 2 cases of autoimmune hemolytic anemia (AIHA) following
      the administration of MF59-adjuvanted influenza vaccine. CASE SUMMARY: An 83-year
      old white woman developed persistent hyperpyrexia, polyarthralgia, and lower limb
      hypostenia about 2 days after receiving influenza vaccine. Clinical signs and
      laboratory evaluations suggested AIHA. The patient was treated with high-dose
      corticosteroids and immunoglobulins, and her clinical condition improved. A 74
      year-old white woman developed severe abdominal pain and asthenia 3 days after
      the administration of influenza vaccine. Clinical signs and laboratory
      evaluations disclosed AIHA. She was treated with corticosteroids, rehydration,
      and blood transfusion; however, she died about 48 hours after hospitalization.
      DISCUSSION: AIHA has been rarely described following influenza vaccine
      administration. In the cases described here, the causal relationship between
      influenza vaccination and the occurrence of AIHA, assessed by means of World
      Health Organization criteria, was scored as probable. It has been proposed that
      the mechanism whereby vaccines induce autoimmune responses can be molecular
      mimicry, although a possible role of other vaccine constituents, with particular
      regard for adjuvants, such as MF59, can not be excluded. Squalene, a constituent
      of MF59, has been suggested as a causative agent of autoimmune reactions.
      However, it is not clear how and under what conditions squalene can cause immune
      responses. CONCLUSIONS: Influenza vaccination may rarely trigger severe AIHA,
      shortly after vaccine administration. A mechanism of molecular mimicry is
      probably involved in the development of these reactions, although the possible
      role of adjuvants can not be excluded. Patients should be instructed to report
      signs and symptoms of autoimmune disorders occurring in the first weeks after
      administration of influenza vaccine.

PMID- 21189365
TI  - Ondansetron-induced dystonia, hypoglycemia, and seizures in a child.
AB  - OBJECTIVE: To document ondansetron-induced dystonia, hypoglycemia, and seizures
      in a child. CASE SUMMARY: A 4-year-old boy was admitted with dystonia following
      an intravenous dose of ondansetron 2 mg (0.13 mg/kg) that he had received for
      vomiting that day. In the emergency department, he developed generalized
      tonicclonic seizures lasting for a few minutes. He was administered lorazepam 1.5
      mg (0.1 mg/kg) to control the seizures. His blood glucose level was 10 mg/dL; the
      hypoglycemia responded promptly to intravenous dextrose 10% (7 mL/kg). Serum
      electrolytes, renal profile, capillary blood gas, and results of a computed
      tomography scan of the brain were normal. Subsequent blood glucose values were
      within normal range. On follow-up after 7 days, the child was healthy with no
      recurrences of the symptoms. A provisional diagnosis of ondansetron-induced acute
      dystonia with seizures and hypoglycemia was made. DISCUSSION: Ondansetron is an
      antiemetic known for its safety profile. There have been a few case reports of
      extrapyramidal adverse effects and seizures from this drug but none of
      ondansetron-associated hypoglycemia. 5-Hydroxytryptamine (5-HT(3)) receptors are
      involved in arginine vasopressin-mediated release of adrenocorticotropin hormone
      and cortisol in response to stress. Blunting of this stress response by
      ondansetron, a 5-HT(3) receptor antagonist, could have caused the hypoglycemia in
      this patient. According to the Naranjo scale, ondansetron was probably the cause
      of the dystonia and seizures, and possibly the cause of the hypoglycemia. Other
      potential explanations for hypoglycemia were considered but were thought to be
      less likely. CONCLUSIONS: Dystonia and seizures have been associated with
      ondansetron in a few case reports. In addition, clinicians need to consider
      hypoglycemia as a possible adverse effect of ondansetron.

PMID- 21189366
TI  - The role of lamotrigine in the treatment of short-lasting unilateral neuralgiform
      headache attacks with conjunctival injection and tearing syndrome.
AB  - OBJECTIVE: To evaluate the efficacy of lamotrigine for treatment of short-lasting
      unilateral neuralgiform headache attacks with conjunctival injection and tearing
      (SUNCT) syndrome. DATA SOURCES: Literature was accessed through MEDLINE (1950
      June 2010) using the terms lamotrigine, triazines, SUNCT, and trigeminal
      autonomic cephalgia. STUDY SELECTION AND DATA EXTRACTION: All articles in English
      and studies conducted in humans were identified and evaluated. DATA SYNTHESIS:
      SUNCT syndrome can be an extremely challenging headache type to manage and has
      been considered refractory to pharmacotherapy. Many anticonvulsants have been
      evaluated as promising SUNCT treatments, with lamotrigine specifically reported
      as an effective first-line treatment option. There is a lack of randomized
      placebo-controlled clinical trials evaluating lamotrigine in SUNCT syndrome
      therapy; however, 2 observational studies, 3 case series, and 5 case reports were
      reviewed. Lamotrigine appears to decrease the frequency and severity of SUNCT
      attacks, leading to complete resolution in some patients. A decrease in symptoms
      was achieved with doses ranging from 25 to 600 mg/day. In some cases, there was
      initial response to low doses, but dosage titrations were often necessary when
      symptoms returned several days after being managed at the same dose. Lamotrigine
      should be initiated at 25 mg/day and gradually titrated, guided by response and
      adverse effects. The risk of Stevens-Johnson syndrome, a dose-related adverse
      effect, can be minimized with gradual titration. CONCLUSIONS: According to case
      reports and observational studies, lamotrigine therapy has resulted in decreased
      frequency or resolution of SUNCT syndrome attacks. Randomized, controlled trials
      are necessary to confirm the efficacy of lamotrigine for this indication.

PMID- 21189367
TI  - Use of risperidone as augmentation treatment for major depressive disorder.
AB  - OBJECTIVE: To review the efficacy and safety of risperidone for augmentation
      treatment in patients with major depressive disorder who fail to achieve adequate
      response to antidepressant monotherapy. DATA SOURCES: A search of MEDLINE (1966
      August 2010) and EMBASE (1980-August 2010) was conducted, using the terms
      risperidone and major depressive disorder. In addition, a manual search of the
      references cited in each publication identified from the database search was
      conducted to identify relevant articles. STUDY SELECTION AND DATA EXTRACTION: All
      English-language, peer-reviewed publications identified from the data sources
      were evaluated. Four clinical trials and 1 subanalysis of a clinical trial were
      included for analysis. DATA SYNTHESIS: Risperidone is an atypical antipsychotic
      that displays antidepressant properties due to its activity at various
      serotonergic and dopaminergic receptors. Studies have demonstrated that
      risperidone augmentation may be effective and safe when used at low doses.
      Although several of the studies identified had limited sample sizes, all studies
      demonstrated improvement on various standardized depressive symptom assessment
      scales. Study durations ranged from 4 to 24 weeks, with doses ranging from 0.25
      to 2 mg/day. The most common adverse effects associated with risperidone therapy
      were headache, dry mouth, and increased appetite. CONCLUSIONS: Clinical evidence
      suggests that the use of risperidone as adjunctive therapy for treatment
      resistant depression may improve rates of response and remission, but long-term
      effectiveness and safety cannot be determined at this time. Therefore, an
      adequate trial of first-line agents from different classes and/or a combination
      of agents from different classes would be recommended prior to initiation of
      risperidone. If the decision is made to start risperidone, health-care providers
      should ensure that patients are educated regarding the potential benefits and
      adverse effects before initiating risperidone.

PMID- 21189368
TI  - Octreotide for symptomatic treatment of diarrhea due to cytomegalovirus colitis.
AB  - OBJECTIVE: To report the improvement of diarrhea in a patient with
      cytomegalovirus (CMV) colitis who was treated with octreotide after failure of
      loperamide. CASE SUMMARY: An 84-year-old male presented with chronic diarrhea and
      CMV colitis; he had been experiencing protracted diarrhea since 2006. In October
      2009 he failed a 21-day course of valgancyclovir 900 mg orally twice daily.
      Several months later, due to continuing diarrhea and progressive malnutrition, a
      colonoscopy and subsequent biopsy again showed CMV. In March 2010 he was started
      on a 28-day course of intravenous ganciclovir 130 mg daily. Three weeks into
      treatment he continued with copious amounts of diarrhea, with no relief from
      loperamide, which was titrated from 2 mg/day to 2 mg every 6 hours. On day 20 of
      ganciclovir treatment he was started on octreotide 50 MUg subcutaneously every 8
      hours; within a few days, the patient began to experience decreased stool
      frequency and consistency. He completed the full 28-day course of ganciclovir,
      with octreotide continuing unchanged, with much improvement in his diarrheal
      symptoms and improvement in appetite, nutritional status, and quality of life.
      DISCUSSION: Studies regarding the treatment of CMV colitis-associated diarrhea
      are scarce, and are typically limited to treating the underlying cause with
      antiviral medications and with the addition of antimotility agents. Three cases
      have been reported in the literature in which octreotide was used for the
      symptomatic treatment of diarrhea, none of which was refractory to loperamide.
      CONCLUSIONS: This is the first known case of a patient with chronic diarrhea due
      to CMV colitis that was unresponsive to loperamide, required protracted antiviral
      treatment (valgancyclovir and gancyclovir), and subsequently experienced relief
      by the use of octreotide 50 MUg subcutaneously every 8 hours.

PMID- 21189369
TI  - Governance: current trends in board education, competencies, and qualifications.
AB  - Hospitals and health system boards have been under enormous pressure to be more
      accountable. However, there is now an emerging trend of voluntary, mandatory, and
      payer-driven board education programs. Currently, 13 states have some type of
      formal, organized board education and development initiative, 10 of which are
      classified as "director and/ or board certificate" or "certification" programs;
      the American Hospital Association (through and with its affiliated Center for
      Healthcare Governance) has issued a Blue Ribbon Panel Report on core
      competencies. Finally, both Congress and the Securities and Exchange Commission
      require publicly traded companies to disclose board and director qualifications.
      This article reviews these emerging trends and posits that these developments are
      a necessary prerequisite not only for accountability and better governance but
      also for quality care.

PMID- 21189370
TI  - Neuron- or glial-specific ablation of secreted renin does not affect renal renin,
      baseline arterial pressure, or metabolism.
AB  - The renin-angiotensin system (RAS), known for its roles in cardiovascular,
      metabolic, and developmental regulation, is present in both the circulation and
      in many individual tissues throughout the body. Substantial evidence supports the
      existence of a brain RAS, though quantification and localization of brain renin
      have been hampered by its low expression levels. We and others have previously
      determined that there are two isoforms of renin expressed in the brain. The
      classical isoform encoding secreted renin (sREN) and a novel isoform encoding
      intracellular renin (icREN), the product of an alternative promoter and first
      exon (exon 1b). The differential role that these two isoforms play in
      cardiovascular and metabolic regulation remains unclear. Here we examined the
      physiological consequences of neuron- and glia-specific knockouts of sREN by
      crossing mice in which the sREN promoter and isoform-specific first exon (exon
      1a) is flanked by LoxP sequences (sREN(flox) mice) with mice expressing Cre
      recombinase controlled by either the neuron-specific Nestin promoter or the glia
      specific GFAP promoter. Resulting offspring exhibited selective knockout of sREN
      in either neurons or glia, while preserving expression of icREN. Consistent with
      a hypothesized role of icREN in the brain RAS, neuron- and glia-specific knockout
      of sREN had no effect on blood pressure or heart rate; food, water, or sodium
      intake; renal function; or metabolic rate. These data demonstrate that sREN is
      dispensable within the brain for normal physiological regulation of
      cardiovascular, hydromineral, and metabolic regulation, and thereby indirectly
      support the importance of icREN in brain RAS function.

PMID- 21189371
TI  - Developmental regulation of mitochondrial biogenesis and function in the mouse
      mammary gland during a prolonged lactation cycle.
AB  - The regulation of mitochondrial biogenesis and function in the lactating mammary
      cell is poorly understood. The goal of this study was to use proteomics to relate
      temporal changes in mammary cell mitochondrial function during lactation to
      changes in the proteins that make up this organelle. The hypothesis tested was
      that changes in mammary cell mitochondrial biogenesis and function during
      lactation would be accounted for by coordinated changes in the proteins of the
      electron transport chain and that some of these proteins might be linked by their
      expression patterns to PPARGC1alpha and AMP kinase. The mitochondrial proteome
      was studied along with markers of mitochondrial biogenesis and function in
      mammary tissue collected from mice over the course of a single prolonged
      lactation cycle. Mammary tissue concentrations of AMP and ADP were increased (P <
      0.05) during early lactation and then declined with prolonged lactation. Similar
      changes were also observed for mitochondrial ATP synthesis activity,
      mitochondrial mass and DNA copy number. Analysis of the mammary cell
      mitochondrial proteome identified 244 unique proteins. Of these, only two
      proteins of the electron transport chain were found to increase during early
      lactation. In contrast, coordinated changes in numerous electron transport chain
      proteins were observed both during mid- and late lactation. There were six
      proteins that could be directly linked to PPARGC1alpha through network analysis.
      Abundance of PPARGC-1alpha and phosphorylation of AMP kinase was highest on day 2
      postpartum. The results suggest that the increases in mammary mitochondria ATP
      synthesis activity during early lactation results from changes in only a limited
      number proteins. In addition, decreases in a handful of proteins linked to lipid
      oxidation could be temporally linked to decreases in PPARGC1alpha and phospho-AMP
      kinase suggesting potential roles for these proteins in coordinating mammary
      gland metabolism during early lactation.

PMID- 21189372
TI  - Can literature enhance oncology training? A pilot humanities curriculum.

PMID- 21189373
TI  - WT1 mutation and 11P15 loss of heterozygosity predict relapse in very low-risk
      wilms tumors treated with surgery alone: a children's oncology group study.
AB  - PURPOSE: Children's Oncology Group defines very low-risk Wilms tumors (VLRWT) as
      stage I favorable histology Wilms tumors weighing less than 550 g in children
      younger than 24 months of age. VLRWTs may be treated with nephrectomy alone.
      However, 10% to 15% of VLRWTs relapse without chemotherapy. Previous studies
      suggest that VLRWTs with low WT1 expression and/or 11p15 loss of heterozygosity
      (LOH) may have increased risk of relapse. The current study validates these
      findings within prospectively identified children with VLRWT who did not receive
      adjuvant chemotherapy. PATIENTS AND METHODS: Fifty-six VLRWTs (10 relapses) were
      analyzed for mutation of WT1, CTNNB1, and WTX; for 11p15 LOH using microsatellite
      analysis; and for H19DMR and KvDMR1 methylation. RESULTS: 11p15 LOH was
      identified in 19 (41%) of 46 evaluable VLRWTs and was significantly associated
      with relapse (P < .001); 16 of 19 were isodisomic for 11p15. WT1 mutation was
      identified in nine (20%) of 45 evaluable VLRWTs and was significantly associated
      with relapse (P = .004); all nine cases also had 11p15 LOH. All evaluable tumors
      showing LOH by microsatellite analysis also showed LOH by methylation analysis.
      Retention of the normal imprinting pattern was identified in 24 of 42 evaluable
      tumors, and none relapsed. Loss of imprinting at 11p15 was identified in one of
      42 tumors. CONCLUSION: WT1 mutation and 11p15 LOH are associated with relapse in
      patients with VLRWTs who do not receive chemotherapy. These may provide
      meaningful biomarkers to stratify patients for reduced chemotherapy in the
      future. VLRWTs show a different incidence of WT1 mutation and 11p15 imprinting
      patterns than has been reported in Wilms tumors of all ages.

PMID- 21189374
TI  - What is the true number needed to screen and treat to save a life with prostate
      specific antigen testing?
AB  - PURPOSE: The European Randomized Study of Screening for Prostate Cancer (ERSPC)
      reported a 20% mortality reduction with prostate-specific antigen (PSA)
      screening. However, they estimated a number needed to screen (NNS) of 1,410 and a
      number needed to treat (NNT) of 48 to prevent one prostate cancer death at 9
      years. Although NNS and NNT are useful statistics to assess the benefits and
      harms of an intervention, in a survival study setting such as the ERSPC, NNS and
      NNT are time specific, and reporting values at one time point may lead to
      misinterpretation of results. Our objective was to re-examine the effect of
      varying follow-up times on NNS and NNT using data extrapolated from the ERSPC
      report. MATERIALS AND METHODS: On the basis of published ERSPC data, we modeled
      the cumulative hazard function using a piecewise exponential model, assuming a
      constant hazard of 0.0002 for the screening and control groups for years 1 to 7
      of the trial and different constant rates of 0.00062 and 0.00102 for the
      screening and control groups, respectively, for years 8 to 12. Annualized cancer
      detection and drop-out rates were also approximated based on the observed number
      of individuals at risk in published ERSPC data. RESULTS: According to our model,
      the NNS and NNT at 9 years were 1,254 and 43, respectively. Subsequently, NNS
      decreased from 837 at year 10 to 503 at year 12, and NNT decreased from 29 to 18.
      CONCLUSION: Despite the seemingly simplistic nature of estimating NNT, there is
      widespread misunderstanding of its pitfalls. With additional follow-up in the
      ERSPC, if the mortality difference continues to grow, the NNT to save a life with
      PSA screening will decrease.

PMID- 21189375
TI  - Troponin I as a predictor for trastuzumab-related cardiotoxicity: current data do
      not provide mechanistic insights or allow for incorporation into clinical
      practice.

PMID- 21189376
TI  - A thought-provoking retrospective study on survival and toxicity after
      reirradiation for recurrent high-grade gliomas.

PMID- 21189377
TI  - Pediatric end-of-life care for Taiwanese children who died as a result of cancer
      from 2001 through 2006.
AB  - PURPOSE: Patterns of aggressive end-of-life (EOL) care have not been extensively
      explored in a pediatric cancer population, especially outside Western countries.
      The purpose of this population-based study was to examine trends in aggressive
      pediatric EOL cancer care in Taiwan. METHODS: Retrospective cohort study that
      used administrative data among 1,208 pediatric cancer decedents from 2001 through
      2006. RESULTS: Taiwanese pediatric cancer patients who died in 2001 through 2006
      received aggressive EOL care. The majority of these patients in their last month
      of life continued to receive chemotherapy (52.5%), used intensive care (57.0%),
      underwent intubation (40.9%), underwent mechanical ventilation (48.2%), or spent
      greater than 14 days (69.5%) in hospital, and they died in an acute care hospital
      (78.8%). Of these pediatric cancer patients, one in four received cardiopulmonary
      resuscitation in the month before they died, and only 7.2% received hospice care.
      Among those who received hospice care, 21.8% started such care within the last 3
      days of life. This pattern of aggressive EOL care did not change over the study
      period except for significantly decreased intubation in the last month of life.
      CONCLUSION: Continued chemotherapy and heavy use of life-sustaining treatments in
      the last month of life coupled with lack of hospice care to support Taiwanese
      pediatric cancer patients dying at home may lead to multiple unplanned health
      care encounters, prolonged hospitalization at EOL, and eventual death in an acute
      care hospital for the majority of these patients. Future research should design
      interventions that enable Taiwanese pediatric cancer patients to receive EOL care
      that best meets the individual or the parental needs and preferences.

PMID- 21189378
TI  - mTOR inhibitor treatment of pancreatic cancer in a patient With Peutz-Jeghers
      syndrome.

PMID- 21189379
TI  - Durable complete remission induced by cetuximab monotherapy in a patient infected
      with HIV and diagnosed with recurrent squamous cell carcinoma of the head and
      neck.

PMID- 21189380
TI  - Phase II study of modified docetaxel, cisplatin, and fluorouracil with
      bevacizumab in patients with metastatic gastroesophageal adenocarcinoma.
AB  - PURPOSE: To evaluate the safety and efficacy of a modified administration
      schedule of docetaxel, cisplatin, and fluorouracil (mDCF) with bevacizumab in
      patients with advanced gastroesophageal malignancies. PATIENTS AND METHODS:
      Previously untreated patients with metastatic gastroesophageal adenocarcinoma
      received bevacizumab 10 mg/kg, docetaxel 40 mg/m2, fluorouracil 400 mg/m2,
      leucovorin 400 mg/m2 on day 1, fluorouracil 1,000 mg/m2/d * 2 days intravenous
      continuous infusion beginning on day 1, and cisplatin 40 mg/m2 on day 3. The
      primary objective was to improve 6-month progression-free survival (PFS) from 43%
      (historical DCF control) to 63% with the addition of bevacizumab. The target
      accrual was 44 patients to have 10% type I and II error rates. RESULTS: In total,
      44 eligible patients with cancer were enrolled from October 2006 to October 2008:
      22 gastric, 20 gastroesophageal junction (GEJ), and two esophagus. In 39 patients
      with measurable disease, the confirmed response rate was 67% (95% CI, 50% to
      81%). Six-month PFS was 79% (95% CI, 63% to 88%), and median PFS was 12 months
      (95% CI, 8.8 to 18.2 months). With 26-month follow-up, median overall survival
      (OS) was 16.8 months (95% CI, 12.1 to 26.1 months), and 2-year survival was 37%.
      Treatment-related grade 3 to 4 toxicity was as follows: neutropenia without fever
      (50%), fatigue (25%), venous thromboembolism (39%), and nausea, vomiting,
      mucositis, neuropathy, and febrile neutropenia less than 10% each. In subset
      analysis, diffuse gastric cancer had significantly worse PFS and OS, and the
      response rate in proximal/GEJ tumors was 85% (95% CI, 62% to 97%). CONCLUSION:
      mDCF with bevacizumab appears tolerable and has notable patient outcomes in
      patients with advanced gastroesophageal adenocarcinoma. Six-month PFS was 79%,
      surpassing our predefined efficacy end point, and median and 2-year OS were 16.8
      months and 37%, respectively.

PMID- 21189381
TI  - Intravenous calcium and magnesium for oxaliplatin-induced sensory neurotoxicity
      in adjuvant colon cancer: NCCTG N04C7.
AB  - PURPOSE: Cumulative sensory neurotoxicity (sNT) is the dose-limiting toxicity of
      oxaliplatin, which commonly leads to early discontinuation of oxaliplatin-based
      therapy in the palliative and adjuvant settings. In a nonrandomized,
      retrospective study, intravenous (IV) calcium/magnesium (Ca/Mg) was associated
      with reduced oxaliplatin-induced sNT. METHODS: Patients with colon cancer
      undergoing adjuvant therapy with infusional fluorouracil, leucovorin, and
      oxaliplatin (FOLFOX) were randomly assigned to Ca/Mg (1g calcium gluconate plus
      1g magnesium sulfate pre- and post-oxaliplatin) or placebo, in a double-blinded
      manner. The primary end point was the percentage of patients with grade 2 or
      greater sNT at any time during or after oxaliplatin-based therapy by National
      Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE;
      version 3) criteria. An oxaliplatin-specific sNT scale and patient questionnaires
      were also used to assess sNT. After 104 of 300 planned patients were enrolled,
      the study was closed. This was due to preliminary reports from another trial that
      suggested that Ca/Mg decreased treatment efficacy; these data were subsequently
      found to be incorrect. RESULTS: Overall, 102 patients were available for
      analysis. Ca/Mg decreased the incidence of chronic, cumulative, grade 2 or
      greater sNT, as measured by NCI CTCAE (P = .038) and also by the oxaliplatin
      specific sNT scale (P = .018). In addition, acute muscle spasms associated with
      oxaliplatin were significantly reduced (P = .01) No effect on acute, cold-induced
      sNT was found. No substantial differences in adverse effects were noted between
      Ca/Mg and placebo. CONCLUSION: Despite early termination and decreased
      statistical power, this study supports IV Ca/Mg as an effective neuroprotectant
      against oxaliplatin-induced cumulative sNT in adjuvant colon cancer.

PMID- 21189382
TI  - Second primary cancers after an index head and neck cancer: subsite-specific
      trends in the era of human papillomavirus-associated oropharyngeal cancer.
AB  - PURPOSE: Patients with head and neck squamous cell carcinoma (HNSCC) are at
      elevated risk of second primary malignancies (SPM), most commonly of the head and
      neck (HN), lung, and esophagus. Our objectives were to identify HNSCC subsite
      specific differences in SPM risk and distribution and to describe trends in risk
      over 3 decades, before and during the era of human papillomavirus (HPV) 
      associated oropharyngeal SCC. METHODS: Population-based cohort study of 75,087
      patients with HNSCC in the Surveillance, Epidemiology, and End Results (SEER)
      program. SPM risk was quantified by using standardized incidence ratios (SIRs),
      excess absolute risk (EAR) per 10,000 person-years at risk (PYR), and number
      needed to observe. Trends in SPM risk were analyzed by using joinpoint log-linear
      regression. RESULTS: In patients with HNSCC, the SIR of second primary solid
      tumor was 2.2 (95% CI, 2.1 to 2.2), and the EAR was 167.7 cancers per 10,000 PYR.
      The risk of SPM was highest for hypopharyngeal SCC (SIR, 3.5; EAR, 307.1 per
      10,000 PYR) and lowest for laryngeal SCC (SIR, 1.9; EAR, 147.8 per 10,000 PYR).
      The most common SPM site for patients with oral cavity and oropharynx SCC was HN;
      for patients with laryngeal and hypopharyngeal cancer, it was the lung. Since
      1991, SPM risk has decreased significantly among patients with oropharyngeal SCC
      (annual percentage change in EAR, -4.6%; P = .03). CONCLUSION: In patients with
      HNSCC, the risk and distribution of SPM differ significantly according to subsite
      of the index cancer. Before the 1990s, hypopharynx and oropharynx cancers carried
      the highest excess risk of SPM. Since then, during the HPV era, SPM risk
      associated with oropharyngeal SCC has declined to the lowest risk level of any
      subsite.

PMID- 21189383
TI  - Diagnostic pitfalls of rare urinary bladder tumors: differential diagnosis of
      lymphoma-like carcinoma of the bladder--a clinicopathologic study and literature
      review.

PMID- 21189384
TI  - Randomized phase II trial of adjuvant hepatic arterial infusion and systemic
      chemotherapy with or without bevacizumab in patients with resected hepatic
      metastases from colorectal cancer.
AB  - PURPOSE: Add systemic bevacizumab (Bev) to adjuvant hepatic arterial infusion
      (HAI) plus systemic therapy after liver resection to increase recurrence-free
      survival (RFS). PATIENTS AND METHODS: Patients were randomly assigned to HAI plus
      systemic therapy with or without Bev. If 1-year RFS of >= 80% was obtained in Bev
      arm, then the regimen would be studied further. HAI with fluorodeoxyuridine plus
      dexamethasone was given on days 1 to 14 of a 5-week cycle. Systemic therapy and
      Bev 5 mg/kg was delivered on days 15 and 29: oxaliplatin 85 mg/m2, leucovorin 400
      mg/m2, and fluorouracil 2,000 mg/m2 infusion for 2 days (if patients received
      prior oxaliplatin, then irinotecan 150 mg/m2 was used). RFS and survival were
      estimated by using the Kaplan-Meier method and compared by using the log-rank
      test. RESULTS: The two arms had similar characteristics: synchronous disease (66%
      v 63%), more than one metastasis (84% v 74%), and clinical risk score >= 3 (50% v
      46%) for no Bev versus Bev arms, respectively. With a median follow-up of 30
      months, 4-year survival was 85% and 81% (P = .5), and 4-year RFS was 46% versus
      37%; 1-year RFS was 83% and 71% (P = .4) for no Bev versus Bev arms. Bilirubin >
      3 mg/dL was seen in zero of 38 versus five of 35 patients (P = .02) and biliary
      stents were placed in zero versus four patients (P = .05) in no Bev versus Bev
      arms. CONCLUSION: The addition of Bev to adjuvant HAI plus systemic therapy after
      liver resection did not seem to increase RFS or survival but appeared to increase
      biliary toxicity. Four-year survival was 85% and 81% for no Bev and Bev arms,
      respectively.

PMID- 21189385
TI  - Single-agent lenalidomide in the treatment of previously untreated chronic
      lymphocytic leukemia.
AB  - PURPOSE: Lenalidomide is an oral immunomodulatory drug with multiple effects on
      the immune system and tumor cell microenvironment leading to inhibition of
      malignant cell growth. Based on encouraging reports of lenalidomide in relapsed
      and refractory chronic lymphocytic leukemia (CLL), we investigated the first-line
      use of single-agent lenalidomide in CLL. PATIENTS AND METHODS: Using a starting
      dose of lenalidomide 10 mg/d for 21 days of a 28-day cycle and weekly 5-mg dose
      escalations to a target of 25 mg, we encountered severe toxicities (tumor lysis,
      fatal sepsis) in the first two patients enrolled. The study was halted and the
      protocol amended to a more conservative regimen: starting dose of lenalidomide
      2.5 mg with monthly escalations to a target dose of 10 mg, and extended tumor
      lysis prophylaxis and monitoring. Gene expression profiles from patient samples
      before and after 7 days of lenalidomide were performed. RESULTS: Twenty-five
      patients were enrolled on the amended protocol. No further tumor lysis events
      were reported. Tumor flare was common (88%) but mild. Grade 3 to 4 neutropenia
      occurred in 72% of patients, with only five episodes of febrile neutropenia. The
      overall response rate was 56% (no complete responses). Although rapid peripheral
      lymphocyte reductions were observed, rebound lymphocytoses during the week off
      therapy were common. Lenalidomide-induced molecular changes enriched for
      cytoskeletal and immune-related genes were identified. CONCLUSION: Lenalidomide
      is clinically active as first-line CLL therapy and is well-tolerated if a
      conservative approach with slow dose escalation is used. A lenalidomide-induced
      molecular signature provides insights into its immunomodulatory mechanisms of
      action in CLL.

PMID- 21189386
TI  - Bronchioloalveolar adenocarcinoma and pulmonary langerhans cell histiocytosis in
      a patient with MUTYH-associated polyposis.

PMID- 21189387
TI  - Risk factors for the development of secondary malignancy after high-dose
      chemotherapy and autograft, with or without rituximab: a 20-year retrospective
      follow-up study in patients with lymphoma.
AB  - PURPOSE: High-dose chemotherapy with peripheral blood progenitor cell (PBPC)
      autograft is effective in high-risk lymphoma, particularly with the addition of
      rituximab; however, it is associated with risk of secondary malignancy. These
      issues have been addressed in a series of 1,347 patients with lymphoma treated
      with a high-dose sequential (HDS) program. PATIENTS AND METHODS: A total of 1,024
      patients with B-cell lymphoma, 234 patients with Hodgkin's lymphoma, and 89
      patients with T-cell lymphoma were treated with HDS between 1985 and 2005 at 11
      Gruppo Italiano Terapie Innovative Linfomi centers. HDS was given as salvage
      treatment to 707 patients (52%); 655 patients (49%) received a modified HDS, with
      high-dose cytarabine and two consecutive PBPC harvests. Rituximab-supplemented
      HDS was given to 523 patients (39%). RESULTS: At a median follow-up of 7 years,
      the median overall survival (OS) was 16.2 years; in B-cell lymphoma the OS was
      significantly superior with rituximab HDS compared to HDS alone. The cumulative
      incidence at 5 and 10 years of secondary myelodysplasia/acute leukemia (sMDS/AL)
      were 3.09% and 4.52%, respectively, that of solid tumors were 2.54% and 6.79%,
      respectively. Factors associated with sMDS/AL were male sex and use of the second
      harvest PBPC for the graft; factors found to be associated with solid tumor were
      advanced age, post-HDS radiotherapy, and rituximab addition to HDS. Despite the
      increased risk of solid tumors, rituximab addition to HDS was still associated
      with survival advantages. CONCLUSION: This analysis has relevant implications for
      the design and use of intensive chemoimmunotherapy with autograft. In addition,
      it offers useful insights toward the understanding and prevention of tumor
      development.

PMID- 21189388
TI  - In patients younger than age 55 years with lymph node-negative breast cancer,
      proliferation by mitotic activity index is prognostically superior to adjuvant!
AB  - PURPOSE: In breast cancer, different tools are used for prognostication and
      adjuvant systemic therapy selection. We compared the accuracy of the online
      program Adjuvant!, the Norwegian Breast Cancer Group (NBCG) guidelines, and the
      proliferation factor mitotic activity index (MAI) in patients with lymph node
      (LN) -negative disease (pN0). PATIENTS AND METHODS: Adjuvant! and MAI thresholds
      were set to 90% to 95% breast cancer-specific survival (BCSS) rates. These
      thresholds were 95% for Adjuvant!, 3 for MAI, and as follows for NBCG: pT1 grade
      1 + pT1a-b grade 2 to 3; all pN0M0 and estrogen receptor/progesterone receptor
      positive versus all others. In 516 patients younger than age 55 years (T1-3N0M0)
      without adjuvant systemic therapy, univariable and multivariable 10-year BCSS
      rates were estimated. RESULTS: Median follow-up time was 118 months. The
      concordance between MAI and Adjuvant! or NBCG was fair (kappa = 0.35 and kappa =
      0.29, respectively). Adjuvant!, NBCG, and MAI were all prognostically significant
      (P <= .001). In the univariable analysis, the 10-year BCSS of MAI less than 3
      versus >= 3 was 95% v 71%, respectively, with a hazard ratio of 7.0. In
      multivariable analysis, MAI was superior to Adjuvant! and NBCG. The 10-year
      survival of Adjuvant! >= 95% versus less than 95% was 91% v 74%, respectively,
      but stratification by MAI identified subgroups with different prognosis. Similar
      results occurred for NBCG and MAI. Adjuvant! and NBCG were not prognostic to each
      other. CONCLUSION: MAI is superior to Adjuvant! and NBCG in prognostication of
      patients with LN-negative breast cancer younger than age 55 years.

PMID- 21189389
TI  - Cardiac troponin cutoffs: the importance of assay sensitivity and the patient
      population.

PMID- 21189390
TI  - WT1 synonymous single nucleotide polymorphism rs16754 correlates with higher mRNA
      expression and predicts significantly improved outcome in favorable-risk
      pediatric acute myeloid leukemia: a report from the children's oncology group.
AB  - PURPOSE: To analyze the prevalence and clinical implications of Wilms' tumor 1
      (WT1) single nucleotide polymorphism (SNP) rs16754 in the context of other
      prognostic markers in pediatric acute myeloid leukemia (AML). PATIENTS AND
      METHODS: Available diagnostic marrow specimens (n = 790) from 1,328 patients
      enrolled in three consecutive Children's Cancer Group/Children's Oncology Group
      trials were analyzed for the presence of SNP rs16754. SNP status was correlated
      with disease characteristics, WT1 expression level, and clinical outcome.
      RESULTS: SNP rs16754 was present in 229 (29%) of 790 patients. The SNP was
      significantly more common in Asian and Hispanic patients and less common in white
      patients (P < .001). SNP rs16754 was also less common in patients with inv(16) (P
      = .043) and more common in patients with -5/del(5q) (P = .047). WT1 expression
      levels were significantly higher in patients with rs16754 or with WT1 mutations
      compared with WT1 wild-type patients (P = .021). Five-year overall survival (OS)
      for patients with and without the SNP was 60% and 50%, respectively (P = .031).
      Prognostic assessment by risk group demonstrated that in patients with low-risk
      disease, OS for those with and without SNP rs16754 was 90% versus 64% (P < .001)
      with a corresponding disease-free survival of 72% versus 53% (P = .041).
      CONCLUSION: The presence of SNP rs16754 was an independent predictor of improved
      OS; outcome differences were most pronounced in the low-risk subgroup. The high
      prevalence of WT1 SNP rs16754, and its correlation with improved outcome,
      identifies WT1 SNP rs16754 as a potentially important molecular marker of
      prognosis in pediatric AML.

PMID- 21189391
TI  - Familial risks in cancer of unknown primary: tracking the primary sites.
AB  - PURPOSE: Cancer of unknown primary (CUP) is diagnosed at the metastatic stage,
      and despite extensive diagnostic work-up, the primary tumor often remains
      unidentified. No data are available on familial clustering of CUP. We hypothesize
      that familial clustering of CUP with other cancers may be informative of the
      primary sites. PATIENTS AND METHODS: A total of 35,168 patients with CUP were
      identified in the Swedish Family-Cancer Database, and risks between family
      members were calculated for concordant (CUP-CUP) and discordant (CUP-any other
      cancer) cancers using standardized incidence ratio (SIR). RESULTS: Familial cases
      of CUP accounted for 2.8% of all CUP cases in the offspring generation. Familial
      SIR for CUP was 1.69 when a sibling was diagnosed with CUP. As to discordant
      associations between siblings, CUP was associated with lung (SIR, 1.87), kidney
      (SIR, 1.82), liver (SIR, 1.67), ovarian (SIR, 1.45), colorectal (SIR, 1.26), and
      breast (SIR, 1.15) cancers and melanoma (SIR, 1.26). Upper aerodigestive tract,
      bladder, pancreatic, and prostate cancers were additionally associated with CUP.
      Notably, CUP was associated with families of kidney, lung, and colorectal
      cancers. CONCLUSION: The present data show that CUP is not a disease of random
      metastatic cancers but, instead, a disease of a defined set of cancers. The
      association of CUP with families of kidney, lung, and colorectal cancers suggests
      a marked genetic basis and shared metastatic mechanisms by many cancer types.
      Familial sites shared by CUP generally match those arising in tissue-of-origin
      determinations and, hence, suggest sites of origin for CUP. Mechanistic
      exploration of CUP may provide insight into defense against primary tumors and
      the metastatic process.

PMID- 21189392
TI  - Baseline preadjuvant magnetic resonance imaging for response assessment and for
      planning radiotherapy in glioblastoma.

PMID- 21189393
TI  - Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell
      lymphoma and mantle cell lymphoma.
AB  - PURPOSE: The proteasome inhibitor bortezomib may enhance activity of
      chemoimmunotherapy in lymphoma. We evaluated dose-escalated bortezomib plus
      standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus
      rituximab (R) in patients with diffuse large B-cell lymphoma (DLBCL) and mantle
      cell lymphoma (MCL). PATIENTS AND METHODS: Seventy-six subjects with untreated
      DLBCL (n = 40) and MCL (n = 36) received standard CHOP every 21 days (CHOP-21)
      with R plus bortezomib at 0.7 mg/m(2) (n = 4), 1.0 mg/m(2) (n = 9), or 1.3
      mg/m(2) (n = 63) on days 1 and 4 for six cycles. RESULTS: Median age was 63 years
      (range, 20 to 87), and International Prognostic Index (IPI) scores were generally
      unfavorable (39% with IPI of 2, and 49% with IPI of 3 to 5), as were Mantle Cell
      Lymphoma International Prognostic Index scores in patients with MCL (28%
      intermediate risk and 39% high risk). Toxicity was manageable, including
      neuropathy in 49 subjects (8% grade 2 and 4% grade 3) and grade 3/4 anemia (13%),
      neutropenia (41%), and thrombocytopenia (25%). For DLBCL, the evaluable overall
      response rate (ORR) was 100% with 86% complete response (CR)/CR unconfirmed (CRu;
      n = 35). Intent-to-treat (ITT, n = 40) ORR was 88% with 75% CR/CRu, 2-year
      progression-free survival (PFS) of 64% (95% CI, 47% to 77%) and 2-year overall
      survival (OS) of 70% (95% CI, 53% to 82%). For MCL, the evaluable ORR was 91%
      with 72% CR/CRu (n = 32). The ITT (n = 36) ORR was 81% with 64% CR/CRu, 2-year
      PFS 44% (95% CI, 27% to 60%) and 2-year OS 86% (95% CI, 70% to 94%). IPI and MIPI
      correlated with survival in DLBCL and MCL, respectively. Unlike in DLBCL treated
      with R-CHOP alone, nongerminal center B cell (non-GCB) and GCB subtypes had
      similar outcomes. CONCLUSION: Bortezomib with R-CHOP-21 can be safely
      administered and may enhance outcomes, particularly in non-GCB DLBCL, justifying
      randomized studies.

PMID- 21189394
TI  - Simple rules can improve prognostic accuracy.

PMID- 21189396
TI  - Serum prostate-specific antigen for the early detection of prostate cancer:
      always, never, or only sometimes?

PMID- 21189397
TI  - How long have I got? Estimating typical, best-case, and worst-case scenarios for
      patients starting first-line chemotherapy for metastatic breast cancer: a
      systematic review of recent randomized trials.
AB  - PURPOSE: To estimate scenarios for survival for women with metastatic breast
      cancer (MBC) who are starting chemotherapy. PATIENTS AND METHODS: We sought
      randomized, first-line chemotherapy trials for MBC published from 1999 to 2009.
      We recorded median progression-free survival (PFS) and median overall survival
      (OS) and extracted the following percentiles (represented scenario) from each OS
      curve: 90th (worst-case), 75th (lower-typical), 25th (upper-typical), and 10th
      (best-case). We also estimated these scenarios for each OS curve by multiplying
      its median by four simple multiples: 0.25 (worst-case), 0.5 (lower-typical), 2
      (upper-typical), and 3 (best-case). Estimates were deemed accurate if they were
      within 0.75 to 1.33 times the actual value. RESULTS: From 36 trials (13,083
      women), the mean for median PFS was 7.6 months (interquartile range [IQR], 6.0 to
      9.0 months), the mean for median OS was 21.7 months (IQR,18.2 to 24.0 months),
      and the mean for the ratio of median OS to median PFS was 3.0 (IQR, 2.4 to 3.5).
      The mean for each OS scenario was worst-case, 6.3 months (IQR, 4.8 to 7.5
      months); lower-typical, 11.9 months (IQR, 9.9 to 13.2 months); upper-typical,
      36.2 months (IQR, 31.1 to 41.3 months); and best-case, 55.8 months (IQR, 47.5 to
      60.2 months). Simple multiples of the median gave accurate estimates of the worst
      case scenario in 73% of OS curves, lower-typical in 97%, upper-typical in 95%,
      and best-case in 96%. OS was longer in trials with higher proportions of estrogen
      receptor-positive tumors (P = .001) and in trials of trastuzumab-treated human
      epidermal growth factor receptor 2-positive tumors (P = .001). CONCLUSION: Simple
      multiples of an OS curve's median can accurately estimate typical (half to double
      the median), best-case (triple the median), and worst-case (one quarter of the
      median) scenarios for survival.

PMID- 21189395
TI  - Alteration of topoisomerase II-alpha gene in human breast cancer: association
      with responsiveness to anthracycline-based chemotherapy.
AB  - PURPOSE: Approximately 35% of HER2-amplified breast cancers have coamplification
      of the topoisomerase II-alpha (TOP2A) gene encoding an enzyme that is a major
      target of anthracyclines. This study was designed to evaluate whether TOP2A gene
      alterations may predict incremental responsiveness to anthracyclines in some
      breast cancers. METHODS: A total of 4,943 breast cancers were analyzed for
      alterations in TOP2A and HER2. Primary tumor tissues from patients with
      metastatic breast cancer treated in a trial of chemotherapy plus/minus
      trastuzumab were studied for amplification/deletion of TOP2A and HER2 as a test
      set followed by evaluation of malignancies from two separate, large trials for
      changes in these same genes as a validation set. Association between these
      alterations and clinical outcomes was determined. RESULTS: Test set cases
      containing HER2 amplification treated with doxorubicin and cyclophosphamide (AC)
      plus trastuzumab, demonstrated longer progression-free survival compared to those
      treated with AC alone (P = .0002). However, patients treated with AC alone whose
      tumors contain HER2/TOP2A coamplification experienced a similar improvement in
      survival (P = .004). Conversely, for patients treated with paclitaxel, HER2/TOP2A
      coamplification was not associated with improved outcomes. These observations
      were confirmed in a larger validation set, where HER2/TOP2A coamplification was
      again associated with longer survival when only anthracycline-containing
      chemotherapy was used for treatment compared with outcome in HER2-positive
      cancers lacking TOP2A coamplification. CONCLUSION: In a study involving nearly
      5,000 breast malignancies, both test set and validation set demonstrate that
      TOP2A coamplification, not HER2 amplification, is the clinically useful
      predictive marker of an incremental response to anthracycline-based chemotherapy.
      Absence of HER2/TOP2A coamplification may indicate a more restricted efficacy
      advantage for breast cancers than previously thought.

PMID- 21189398
TI  - Acral metastases from laryngeal carcinoma.

PMID- 21189399
TI  - Conjunctival melanoma: bladder and upper urinary tract metastases.

PMID- 21189400
TI  - Deciphering the roles of tissue renin-angiotensin systems in whole animals.

PMID- 21189401
TI  - Efficacy and duration of benazepril plus amlodipine or hydrochlorothiazide on 24
      hour ambulatory systolic blood pressure control.
AB  - The combination of benazepril plus amlodipine was shown to be more effective than
      benazepril plus hydrochlorothiazide in reducing cardiovascular events in the
      Avoiding Cardiovascular Events through Combination Therapy in Patients Living
      with Systolic Hypertension (ACCOMPLISH) trial. There was a small difference in
      clinic systolic blood pressure between the treatment arms favoring benazepril
      plus amlodipine. Ambulatory blood pressure monitoring provides a more rigorous
      estimate of blood pressure effects. A subset of 573 subjects underwent ambulatory
      blood pressure monitoring during year 2. Readings were obtained every 20 minutes
      during a 24-hour period. Between-treatment differences (benazepril plus
      amlodipine versus benazepril plus hydrochlorothiazide) in mean values were
      analyzed using ANOVA. Treatment comparisons with respect to categorical variables
      were made using Pearson's chi2. At year 2, the treatment groups did not differ
      significantly in 24-hour mean daytime or nighttime blood pressures (values of
      123.9, 125.9, and 118.1 mm Hg for benazepril plus amlodipine group versus 122.3,
      124.1, and 116.9 for the benazepril plus hydrochlorothiazide group), with mean
      between-group differences of 1.6, 1.8, and 1.2 mm Hg, respectively. Blood
      pressure control rates (24-hour mean systolic blood pressure <130 mm Hg on
      ambulatory blood pressure monitoring) were greater than 80% in both groups.
      Nighttime systolic blood pressure provided additional risk prediction after
      adjusting for the effects of drugs. The 24-hour blood pressure control was
      similar in both treatment arms, supporting the interpretation that the difference
      in cardiovascular outcomes favoring a renin angiotensin system blocker combined
      with amlodipine rather than hydrochlorothiazide shown in the ACCOMPLISH trial was
      not caused by differences in blood pressure, but instead intrinsic properties
      (metabolic or hemodynamic) of the combination therapies.

PMID- 21189402
TI  - Gender differences in pressure-natriuresis and renal autoregulation: role of the
      Angiotensin type 2 receptor.
AB  - Sexual dimorphism in arterial pressure regulation has been observed in humans and
      animal models. The mechanisms underlying this gender difference are not fully
      known. Previous studies in rats have shown that females excrete more salt than
      males at a similar arterial pressure. The renin-angiotensin system is a powerful
      regulator of arterial pressure and body fluid volume. This study examined the
      role of the angiotensin type 2 receptor (AT2R) in pressure-natriuresis in male
      and female rats because AT2R expression has been reported to be enhanced in
      females. Renal function was examined at renal perfusion pressures of 120, 100,
      and 80 mm Hg in vehicle-treated and AT2R antagonist-treated (PD123319; 1 mg/kg/h)
      groups. The pressure-natriuresis relationship was gender-dependent such that it
      was shifted upward in female vs male rats (P < 0.001). AT2R blockade modulated
      the pressure-natriuresis relationship, shifting the curve downward in male (P <
      0.01) and female (P < 0.01) rats to a similar extent. In females, AT2R blockade
      also reduced the lower end of the autoregulatory range of renal blood flow (P <
      0.05) and glomerular filtration rate (P < 0.01). Subsequently, the renal blood
      flow response to graded angiotensin II infusion was also measured with and
      without AT2R blockade. We found that AT2R blockade enhanced the renal
      vasoconstrictor response to angiotensin II in females but not in males (P <
      0.05). In conclusion, the AT2R modulates pressure-natriuresis, allowing the same
      level of sodium to be excreted at a lower pressure in both genders. However, a
      gender-specific role for the AT2R in renal autoregulation was evident in females,
      which may be a direct vascular AT2R effect.

PMID- 21189403
TI  - C-type natriuretic peptide and cardiac fibrosis.

PMID- 21189404
TI  - Prevention of angiotensin II-mediated renal oxidative stress, inflammation, and
      fibrosis by angiotensin-converting enzyme 2.
AB  - Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase capable of
      metabolizing angiotensin (Ang) II into Ang 1 to 7. We hypothesized that ACE2 is a
      negative regulator of Ang II signaling and its adverse effects on the kidneys.
      Ang II infusion (1.5 mg/kg-1/d-1) for 4 days resulted in higher renal Ang II
      levels and increased nicotinamide adenine dinucleotide phosphate oxidase activity
      in ACE2 knockout (Ace2(-/y)) mice compared to wild-type mice. Expression of
      proinflammatory cytokines, interleukin-1beta and chemokine (C-C motif) ligand 5,
      were increased in association with greater activation of extracellular-regulated
      kinase 1/2 and increase of protein kinase C-alpha levels. These changes were
      associated with increased expression of fibrosis-associated genes (alpha-smooth
      muscle actin, transforming growth factor-beta, procollagen type Ialpha1) and
      increased protein levels of collagen I with histological evidence of increased
      tubulointerstitial fibrosis. Ang II-infused wild-type mice were then treated with
      recombinant human ACE2 (2 mg/kg-1/d-1, intraperitoneal). Daily treatment with
      recombinant human ACE2 reduced Ang II-induced pressor response and normalized
      renal Ang II levels and oxidative stress. These changes were associated with a
      suppression of Ang II-mediated activation of extracellular-regulated kinase 1/2
      and protein kinase C pathway and Ang II-mediated renal fibrosis and T-lymphocyte
      mediated inflammation. We conclude that loss of ACE2 enhances renal Ang II levels
      and Ang II-induced renal oxidative stress, resulting in greater renal injury,
      whereas recombinant human ACE2 prevents Ang II-induced hypertension, renal
      oxidative stress, and tubulointerstitial fibrosis. ACE2 is an important negative
      regulator of Ang II-induced renal disease and enhancing ACE2 action may have
      therapeutic potential for patients with kidney disease.

PMID- 21189406
TI  - Pathways leading to atherosclerosis: a structural equation modeling approach in
      young adults.
AB  - Several risk factors of cardiovascular diseases have been studied using direct
      association measures. Because the incidence of obesity and cardiovascular
      diseases is rising, it is important to correctly model these risk factors
      involved in development of cardiovascular diseases. Until now, statistical
      methods lacked to achieve this goal because of complex interrelationships
      involved. Structural Equation Modeling (SEM) is an advanced statistical technique
      that enables solving this issue. The aims of this study were to investigate
      whether SEM could unravel pathways involved in cardiovascular diseases and to
      visualize these pathways in a model. In 322 healthy participants of the PROGRAM
      (PROgramming factors for GRowth And Metabolism) study, 18 to 24 years of age, we
      explored pathways leading to atherosclerosis measured by carotid intima-media
      thickness. Using SEM, we were able to model these pathways for males and females
      using body fat percentage, serum lipid levels, and blood pressure. We are the
      first to present a model of complex direct and indirect effects of fat mass
      leading to atherosclerosis using SEM. Both male and female path-model had an
      excellent fit. Fat mass had a significant effect on carotid intima-media
      thickness through various pathways, with the largest effect size on carotid
      intima-media thickness via blood pressure. SEM showed that the pathways differed
      between males and females, with a larger effect of serum lipids on carotid intima
      media thickness in males. In conclusion, SEM is suitable in identifying models to
      unravel potential causal pathways in complex origins of diseases. We present a
      model involving several pathways, showing that fat mass has an influence on risk
      factors for atherosclerosis, already at 21 years of age.

PMID- 21189405
TI  - Angiotensin AT2 receptor stimulation inhibits early renal inflammation in
      renovascular hypertension.
AB  - Angiotensin II type 2 receptor (AT2R) counteracts most effects of angiotensin II
      type 1 receptor (AT(1)R). We hypothesized that direct AT2R stimulation reduces
      renal production of the inflammatory cytokines tumor necrosis factor-alpha (TNF
      alpha), interleukin-6 (IL-6), and transforming growth factor-beta1 (TGF-beta1)
      and enhances the production of nitric oxide (NO) and cyclic guanosine 3',5'
      monophosphate (cGMP) in the clipped kidney of 2-kidney, 1-clip (2K1C)
      hypertension rat model. We used Sprague-Dawley rats to evaluate changes in renal
      interstitial fluid recovery levels of TNF-alpha, IL-6, NO, and cGMP; renal
      expression of AT1R, AT2R, TGF-beta1, TNF-alpha, and IL-6 in sham and 2K1C rats
      treated for 4 days with vehicle, AT2R agonist compound 21 (C21), or AT2R
      antagonist PD123319 (PD), alone and combined (n=6, each group). Systolic blood
      pressure increased significantly in 2K1C and was not influenced by any treatment.
      Clipped kidneys showed significant increases in renal expression of AT1R, AT2R,
      TNF-alpha, IL-6, TGF-beta1 and decreases in NO and cGMP levels. These factors
      were not influenced by PD treatment. In contrast, C21 caused significant decrease
      in renal TNF-alpha, IL-6, TGF-beta1 and an increase in NO and cGMP levels.
      Combined C21 and PD treatment partially reversed the observed C21 effects.
      Compared to sham, there were no significant changes in TNF-alpha, IL-6, TGF
      beta1, NO, or cGMP in the nonclipped kidneys of 2K1C animals. We conclude that
      direct AT2R stimulation reduces early renal inflammatory responses and improves
      production of NO and cGMP in renovascular hypertension independent of blood
      pressure reduction.

PMID- 21189407
TI  - Placebo-controlled trials of blood pressure-lowering therapies for primary
      prevention of dementia.

PMID- 21189408
TI  - The aging heart, myocardial fibrosis, and its relationship to circulating C-type
      natriuretic Peptide.
AB  - Myocardial aging is characterized by left ventricular (LV) fibrosis leading to
      diastolic and systolic dysfunction. Studies have established the potent
      antifibrotic and antiproliferative properties of C-type natriuretic peptide
      (CNP); however, the relationship between circulating CNP, LV fibrosis, and
      associated changes in LV function with natural aging are undefined. Accordingly,
      we characterized the relationship of plasma CNP with LV fibrosis and function in
      2-, 11-, and 20-month-old male Fischer rats. Further in vitro, we established the
      antiproliferative actions of CNP and the participation of the clearance receptor
      using adult human cardiac fibroblasts. Here we establish for the first time that
      a progressive decline in circulating CNP characterizes natural aging and is
      strongly associated with a reciprocal increase in LV fibrosis that precedes
      impairment of diastolic and systolic function. Additionally, we demonstrate in
      cultured adult human cardiac fibroblasts that the direct antiproliferative
      actions of high-dose CNP may involve a non-cGMP pathway via the clearance
      receptor. Together, these studies provide new insights into myocardial aging and
      the relationship to the antifibrotic and antiproliferative peptide CNP.

PMID- 21189410
TI  - FDA offers suggestions for CT safety.

PMID- 21189409
TI  - Osteonecrosis of the jaw and the role of macrophages.
AB  - Nitrogen-containing bisphosphonates have been associated with the development of
      osteonecrosis of the jaws (ONJ), but the lack of reliable epidemiological data
      and appropriate animal models has restricted our understanding of ONJ
      pathophysiology and limited its management. The best available information is
      from histopathologic findings, which implicate bone necrosis and infection,
      although it is not clear which is primary. However, there are data suggesting
      that macrophages could well be the central factor in allowing the infection to
      develop first, followed by local necrosis, which could also account for the
      development of ONJ in patients treated with denosumab, a human monoclonal
      antibody to the receptor activator of nuclear factor-kappaB ligand. This review
      examines the evidence that macrophages could play a prominent role in development
      of ONJ and the proposal that it may be more appropriate to view ONJ as a drug and
      not only a bisphosphonate-related complication.

PMID- 21189411
TI  - How flexible is USP General Chapter <823>?

PMID- 21189414
TI  - Kinetic analysis and quantification of the dopamine transporter in the nonhuman
      primate brain with 11C-PE2I and 18F-FE-PE2I.
AB  - 18F-(E)-N-(3-iodoprop-2-enyl)-2beta-carbofluoroethoxy-3beta- (4'-methyl
      phenyl)nortropane (18F-FE-PE2I) is a novel radioligand for dopamine transporter
      (DAT) PET. As compared with 11C-N-(3-iodoprop-2E-enyl)-2beta-carbomethoxy-3beta
      (4-methylphenyl)nortropane (11C-PE2I), 18F-FE-PE2I shows faster kinetics and more
      favorable metabolism, with less production of a radiometabolite with intermediate
      lipophilicity (M1), which-in the case of 11C-PE2I-has been shown to enter the rat
      brain. In this study, we compared DAT quantification with 11C-PE2I and 18F-FE
      PE2I in nonhuman primates, using kinetic and graphical analysis with the input
      function of both the parent and the radiometabolite, to assess the potential
      contribution of the radiometabolite. METHODS: Three rhesus monkeys were examined
      with 11C-PE2I and 18F-FE-PE2I using the HRRT system. Arterial input functions of
      the parent and radiometabolite M1 were measured. Kinetic and graphical analyses
      were applied using either the parent input (methods 1 and 3) or the parent plus
      radiometabolite input (methods 2 and 4). Outcome measures were distribution
      volumes (VT and VND), specific-to-nondisplaceable tissue radioactivity ratio at
      equilibrium (BPND; parent input), and specific-to-nondisplaceable tissue
      radioactivity ratio at equilibrium in the presence of metabolites (RT; parent
      plus radiometabolite input). RESULTS: 11C-PE2I showed higher distribution volumes
      than 18F-FE-PE2I calculated with methods 1 and 3 (striatal VT, ~300%; VND in
      cerebellum, ~30%). With methods 2 and 4, VT in the striatum was approximately 60%
      higher in the case of 11C-PE2I, whereas no difference in VND was found in the
      cerebellum. For each radioligand, BPND estimated with methods 1 and 3 tended to
      be higher than RT estimated with methods 2 and 4. However, the bias of BPND,
      compared with RT, was much larger for 11C-PE2I (40%-60% in the caudate and
      putamen) than for 18F-FE-PE2I (<10% in the caudate and putamen). CONCLUSION: The
      direct comparison between the radioligands confirmed that 18F-FE-PE2I shows
      faster kinetics and more favorable metabolism than 11C-PE2I. The kinetic and
      graphical analyses with the input function of the parent and radiometabolite
      showed that the bias in BPND was much lower for 18F-FE-PE2I than for 11C-PE2I and
      suggested that the lower production of the radiometabolite M1 would make 18F-FE
      PE2I more suitable for the DAT quantification. Further studies in humans are
      necessary to confirm these findings.

PMID- 21189415
TI  - MRI-assisted PET motion correction for neurologic studies in an integrated MR-PET
      scanner.
AB  - Head motion is difficult to avoid in long PET studies, degrading the image
      quality and offsetting the benefit of using a high-resolution scanner. As a
      potential solution in an integrated MR-PET scanner, the simultaneously acquired
      MRI data can be used for motion tracking. In this work, a novel algorithm for
      data processing and rigid-body motion correction (MC) for the MRI-compatible
      BrainPET prototype scanner is described, and proof-of-principle phantom and human
      studies are presented. METHODS: To account for motion, the PET prompt and random
      coincidences and sensitivity data for postnormalization were processed in the
      line-of-response (LOR) space according to the MRI-derived motion estimates. The
      processing time on the standard BrainPET workstation is approximately 16 s for
      each motion estimate. After rebinning in the sinogram space, the motion corrected
      data were summed, and the PET volume was reconstructed using the attenuation and
      scatter sinograms in the reference position. The accuracy of the MC algorithm was
      first tested using a Hoffman phantom. Next, human volunteer studies were
      performed, and motion estimates were obtained using 2 high-temporal-resolution
      MRI-based motion-tracking techniques. RESULTS: After accounting for the
      misalignment between the 2 scanners, perfectly coregistered MRI and PET volumes
      were reproducibly obtained. The MRI output gates inserted into the PET list-mode
      allow the temporal correlation of the 2 datasets within 0.2 ms. The Hoffman
      phantom volume reconstructed by processing the PET data in the LOR space was
      similar to the one obtained by processing the data using the standard methods and
      applying the MC in the image space, demonstrating the quantitative accuracy of
      the procedure. In human volunteer studies, motion estimates were obtained from
      echo planar imaging and cloverleaf navigator sequences every 3 s and 20 ms,
      respectively. Motion-deblurred PET images, with excellent delineation of specific
      brain structures, were obtained using these 2 MRI-based estimates. CONCLUSION: An
      MRI-based MC algorithm was implemented for an integrated MR-PET scanner. High
      temporal-resolution MRI-derived motion estimates (obtained while simultaneously
      acquiring anatomic or functional MRI data) can be used for PET MC. An MRI-based
      MC method has the potential to improve PET image quality, increasing its
      reliability, reproducibility, and quantitative accuracy, and to benefit many
      neurologic applications.

PMID- 21189416
TI  - A robust protocol to map binding sites of the 14-3-3 interactome: Cdc25C requires
      phosphorylation of both S216 and S263 to bind 14-3-3.
AB  - Modern proteomic techniques have identified hundreds of proteins that bind 14-3
      3s, the most widespread eukaryotic phosphoserine/threonine sensors, but accurate
      prediction of the target phospho-sites is difficult. Here we describe a
      systematic approach using synthetic peptides that tests large numbers of
      potential binding sites in parallel for human 14-3-3. By profiling the sequence
      requirements for three diverse 14-3-3 binding sites (from IRS-1, IRSp53 and
      GIT2), we have generated enhanced bioinformatics tools to score sites and allow
      more tractable testing by co-immunoprecipitation. This approach has allowed us to
      identify two additional sites other than Ser216 in the widely studied cell
      division cycle (Cdc) protein 25C, whose function depends on 14-3-3 binding. These
      Ser247 and Ser263 sites in human Cdc25C, which were not predicted by the existing
      Scansite search, are conserved across species and flank the nuclear localization
      region. Furthermore, we found strong interactions between 14-3-3 and peptides
      with the sequence Rxx[S/T]xR typical for PKC sites, and which is as abundant as
      the canonical Rxx[S/T]xP motif in the proteome. Two such sites are required for
      14-3-3 binding in the polarity protein Numb. A recent survey of >200 reported
      sites identified only a handful containing this motif, suggesting that it is
      currently under-appreciated as a candidate binding site. This approach allows one
      to rapidly map 14-3-3 binding sites and has revealed alternate motifs.

PMID- 21189417
TI  - Discovery of mouse spleen signaling responses to anthrax using label-free
      quantitative phosphoproteomics via mass spectrometry.
AB  - Inhalational anthrax is caused by spores of the bacterium Bacillus anthracis (B.
      anthracis), and is an extremely dangerous disease that can kill unvaccinated
      victims within 2 weeks. Modern antibiotic-based therapy can increase the survival
      rate to ~50%, but only if administered presymptomatically (within 24-48 h of
      exposure). To discover host signaling responses to presymptomatic anthrax, label
      free quantitative phosphoproteomics via liquid chromatography coupled to mass
      spectrometry was used to compare spleens from uninfected and spore-challenged
      mice over a 72 h time-course. Spleen proteins were denatured using urea, reduced
      using dithiothreitol, alkylated using iodoacetamide, and digested into peptides
      using trypsin, and the resulting phosphopeptides were enriched using titanium
      dioxide solid-phase extraction and analyzed by nano-liquid chromatography-Linear
      Trap Quadrupole-Orbitrap-MS(/MS). The fragment ion spectra were processed using
      DeconMSn and searched using both Mascot and SEQUEST resulting in 252,626
      confident identifications of 6248 phosphopeptides (corresponding to 5782
      phosphorylation sites). The precursor ion spectra were deisotoped using Decon2LS
      and aligned using MultiAlign resulting in the confident quantitation of 3265 of
      the identified phosphopeptides. ANOVAs were used to produce a q-value ranked list
      of host signaling responses. Late-stage (48-72 h postchallenge) Sterne strain
      (lethal) infections resulted in global alterations to the spleen phosphoproteome.
      In contrast, DeltaSterne strain (asymptomatic; missing the anthrax toxin)
      infections resulted in 188 (5.8%) significantly altered (q<0.05) phosphopeptides.
      Twenty-six highly tentative phosphorylation responses to early-stage (24 h
      postchallenge) anthrax were discovered (q<0.5), and ten of these originated from
      eight proteins that have known roles in the host immune response. These tentative
      early-anthrax host response signaling events within mouse spleens may translate
      into presymptomatic diagnostic biomarkers of human anthrax detectable within
      circulating immune cells, and could aid in the identification of pathogenic
      mechanisms and therapeutic targets.

PMID- 21189418
TI  - Ultrasonographic and magnetic resonance imaging diagnosis of an oropharyngeal
      wood penetrating injury in a dog.
AB  - A 5 yr old female intact English setter with a 17 day history of a penetrating
      oropharyngeal wound was referred for cervical swelling and pain. Physical
      examination revealed swelling at the left lateral aspect of the cranial cervical
      region. Pain was elicited upon flexion, extension, and leftward movement of the
      neck. Neurologic deficits were not identified. Cervical ultrasonography showed a
      0.4 cm * 2.3 cm linear, hyperechoic structure in the soft tissues ventrolateral
      to the first (C1) and second (C2) cervical vertebrae. MRI demonstrated a linear
      structure 2 cm in length adjacent to the cranial aspect of C2. The foreign
      material was isointense to hyperintense on precontrast T1-weighted images,
      isointense on postcontrast T1-weighted images, and hypointense on T2-weighted
      images relative to adjacent muscle. Abnormalities within the spinal canal were
      not identified. Upon surgical exploration, a reed foreign body was identified
      deep to the serratus ventralis muscle. The patient was normal on follow-up
      evaluations 4 wk postsurgically.

PMID- 21189419
TI  - Craniomandibular osteopathy with a unique neurological manifestation in a young
      Akita.
AB  - This report describes a 4 mo old intact male Akita that presented for evaluation
      of a life-long history of facial swelling and failure to thrive. Physical
      examination revealed an enlarged cranium with prominent bony swellings on the
      maxillary bone, excessive laxity and crepitus involving multiple joints, and
      proprioceptive deficits. Radiographs demonstrated multiple osseous abnormalities
      including endosteal thickening of the femurs and ilium. Necropsy revealed gross
      compression of the cerebellum and brainstem. Physical exam findings, radiographic
      abnormalities, and histopathology of multiple bony lesions were all consistent
      with craniomandibular osteopathy. In this unique case of craniomandibular
      osteopathy, the dog was affected with severe bony proliferations leading to
      generalized hyperostotic lesions and brainstem compression resulting in
      neurologic deficits.

PMID- 21189421
TI  - Social norms and the relationship between cigarette use and religiosity among
      adolescents in the United States.
AB  - This study investigated the social dynamics that underlie the negative
      association between religiosity and cigarette use among U.S. adolescents. Using
      data from the 2007 National Survey on Drug Use and Health, the authors used a
      theory-based conceptual model (vicarious learning networks [VLN]) to examine the
      role that key reference group norms play in the religiosity-smoking relationship.
      This relationship is partially mediated by parents' and close friends' perceived
      disapproval for smoking. However, religiosity maintains a strong negative
      association with smoking. Consistent with the VLN model, cigarette use varied
      substantively based on reference group normative configurations. To the extent
      that the protective effects of religiosity arise from its influence in
      structuring the social milieu, some of religiosity's benefits could potentially
      be leveraged through interventions that promote healthy norms among reference
      groups within the social network. The VLN model may be a useful tool for
      conceptualizing the transmission of health behavior through social learning
      processes.

PMID- 21189420
TI  - Molecular characterization of the NPC1L1 variants identified from cholesterol low
      absorbers.
AB  - Niemann-Pick C1-like 1 (NPC1L1) is an essential protein for dietary cholesterol
      absorption. Nonsynonymous (NS) variants of NPC1L1 in humans have been suggested
      to associate with cholesterol absorption variations. However, information
      concerning the characteristics and mechanism of these variants in cholesterol
      uptake is limited. In this study, we analyzed the cholesterol uptake ability of
      the 19 reported NS variants of NPC1L1 identified from cholesterol low absorbers.
      Among these variants, L110F, R306C, A395V, G402S, T413M, R693C, R1214H, and
      R1268H could partially mediate cellular cholesterol uptake and were categorized
      as partially dysfunctional variants. The other 11 variants including T61M, N132S,
      D398G, R417W, G434R, T499M, S620C, I647N, G672R, S881L, and R1108W could barely
      facilitate cholesterol uptake, and were classified into the severely
      dysfunctional group. The partially dysfunctional variants showed mild defects in
      one or multiple aspects of cholesterol-regulated recycling, subcellular
      localization, glycosylation, and protein stability. The severely dysfunctional
      ones displayed remarkable defects in all these aspects and were rapidly degraded
      through the ER-associated degradation (ERAD) pathway. In vivo analyses using
      adenovirus-mediated expression in mouse liver confirmed that the S881L variant
      failed to localize to liver canalicular membrane, and the mice showed defects in
      biliary cholesterol re-absorption, while the G402S variant appeared to be similar
      to wild-type NPC1L1 in mouse liver. This study suggests that the dysfunction of
      the 19 variants on cholesterol absorption is due to the impairment of recycling,
      subcellular localization, glycosylation, or stability of NPC1L1.

PMID- 21189422
TI  - Strategies to facilitate exposure to internet-delivered health behavior change
      interventions aimed at adolescents or young adults: a systematic review.
AB  - The Internet is considered to be a promising delivery channel of interventions
      aimed at promoting healthful behaviors, especially for adolescents and young
      adults. Exposure to these interventions, however, is generally low. A more
      extensive exploration of methods, strategies, and their effectiveness with regard
      to facilitating exposure is therefore timely, because this knowledge is crucial
      to improve the use of such interventions and, subsequently, to increase
      behavioral change. Therefore, a systematic review of the literature was
      conducted, resulting in 838 studies based on title selection, of which 26 studies
      met the eligibility criteria. The systematic review resulted in an overview of
      methods and strategies that have been used to facilitate exposure. Patterns of
      effective strategies could be observed, such as the combination of tailored
      communication and the use of reminders and incentives. Nevertheless, exposure
      specific theories need to be developed and objective exposure measures should be
      tracked and reported in future studies.

PMID- 21189424
TI  - Effectiveness of valganciclovir 900 mg versus 450 mg for cytomegalovirus
      prophylaxis in transplantation: direct and indirect treatment comparison meta
      analysis.
AB  - BACKGROUND: valganciclovir (VGC) 900 mg is approved for CMV prophylaxis, but it
      has been associated with 10%-40% leucopenia rate. We hypothesize that VGC 450 mg
      daily may be as effective as and safer than 900 mg daily. METHODS: studies
      evaluating valganciclovir 900 mg and 450 mg daily against controls were
      evaluated. Direct comparisons were performed by random-effects models and
      indirect comparisons by the Bucher method. RESULTS: twelve trials with VGC 900 mg
      (1543 patients) and 8 trials with VGC 450 mg (1531 patients) were included. The
      risk of CMV disease with VGC 900 mg versus controls was 1.06 (95% confidence
      interval [CI], .64-1.76; P = .81; I2=29%) and with VGC 450 mg vs controls .77
      (95%CI, .49-1.18; P = .23; I2=24%). The risk of leucopenia was 5.24 (2.09-13.15;
      P = .0004; I2=44%) for VGC 900 mg versus controls and 1.58 (.96-2.61; P = .07;
      I2=36%) for VGC 450 mg versus controls; the risk for acute allograft rejection
      was 1.71 (.45, -6.50; P = .43) for VGC 900 mg and .80 (.50-1.28; P = .34) for VGC
      450 mg. Adjusted indirect comparison between VGC 900 mg and VGC 450mg: the risk
      for CMV disease was not significantly different: odds ratio (OR), 1.38 (.84
      2.25); P = .19; the risk of leucopenia was significantly increased with VGC 900
      mg: 3.32 (1.76-6.26); P = .0002; and the risk of rejection was significantly
      increased with VGC 900 mg: 2.56 (1.50-4.53); P = .0005. Results remained
      consistent after adjustments by allograft, CMV control strategy, and
      immunosuppression. CONCLUSIONS: valganciclovir 900 mg showed no superiority
      efficacy compared to controls (ganciclovir or preemptive) and equivalent efficacy
      to VGC 450 mg (statistical power: 94% and 97%, respectively) for CMV universal
      prophylaxis.VGC 900 mg was significantly associated with 3 times increase in the
      risk of leucopenia and 2 times increase in the risk of rejection compared with
      VGC 450 mg.

PMID- 21189423
TI  - Molecular basis of Wnt activation via the DIX domain protein Ccd1.
AB  - The Wnt signaling plays pivotal roles in embryogenesis and cancer, and the three
      DIX domain-containing proteins, Dvl, Axin, and Ccd1, play distinct roles in the
      initiation and regulation of canonical Wnt signaling. Overexpressed Dvl has a
      tendency to form large polymers in a cytoplasmic punctate pattern, whereas the
      biologically active Dvl in fact forms low molecular weight oligomers. The
      molecular basis for how the polymeric sizes of Dvl proteins are controlled upon
      Wnt signaling remains unclear. Here we show that Ccd1 up-regulates canonical Wnt
      signaling via acting synergistically with Dvl. We determined the crystal
      structures of wild type Ccd1-DIX and mutant Dvl1-DIX(Y17D), which pack into "head
      to-tail" helical filaments. Structural analyses reveal two sites crucial for
      intra-filament homo- and hetero-interaction and a third site for inter-filament
      homo-assembly. Systematic mutagenesis studies identified critical residues from
      all three sites required for Dvl homo-oligomerization, puncta formation, and
      stimulation of Wnt signaling. Remarkably, Ccd1 forms a hetero-complex with Dvl
      through the "head" of Dvl-DIX and the "tail" of Ccd1-DIX, depolymerizes Dvl homo
      assembly, and thereby controls the size of Dvl polymer. These data together
      suggest a molecular mechanism for Ccd1-mediated Wnt activation in that Ccd1
      converts latent polymeric Dvl to a biologically active oligomer(s).

PMID- 21189425
TI  - A "one-two punch" leading to hepatitis C seroconversion.
AB  - We report a case of acute hepatitis C virus infection that occurred after a
      traumatic altercation among prison inmates. This report has significant
      implications for infection control policies and procedures in prisons and jails,
      where the estimated prevalence of hepatitis C virus infection is ~20 times that
      of the general population.

PMID- 21189426
TI  - Interpretation of renal volume in autosomal dominant polycystic kidney disease
      and relevant clinical implications.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is the most common life
      threatening hereditary disease of the kidney. It presents with progressive
      enlargement of the kidneys with numerous cysts that distort the parenchyma and
      result in progressive decline in kidney function. Autosomal dominant polycystic
      kidney disease is genetically modified with the responsible genes localized to
      separate loci on chromosome 16 (PKD1 gene), accounting for the majority of ADPKD
      cases, and chromosome 4 (PKD2 gene), accounting for the remainder. This review
      discusses the current understanding of the pathogenesis of ADPKD, focusing on
      renal volume and its pivotal role on the manifestations of the disease.
      Specifically, activation of the renin-angiotensin-aldosterone system,
      hypertension, left ventricular hypertrophy, kidney function deterioration, pain,
      and hematuria are examined as consequences of renal volume increase. Recent
      developments on diagnostic modalities and criteria of the ADPKD are also
      discussed.

PMID- 21189427
TI  - Dialysis-related factors affecting quality of life in patients on hemodialysis.
AB  - INTRODUCTION. Treatment modalities for end-stage renal disease affect quality of
      life (QOL) of the patients. This study was conducted to assess the QOL of
      patients on hemodialysis and compare it with caregivers of these patients. Cause
      of ESRD and dialysis-related factors affecting QOL were also examined. MATERIALS
      AND METHODS. This cross-sectional study was conducted on patient on maintenance
      hemodialysis for more than 3 months at 3 dialysis centers of Lahore. Fifty
      healthy individuals were included as controls from among the patients'
      caregivers. The QOL index was measured using the World Health Organization QOL
      questionnaire, with higher scores corresponding to better QOL of patients.
      RESULTS. Eighty-nine patients (71.2%) were men, 99 (79.2%) were married, 75
      (60.0%) were older than 45 years, and 77 (61.6%) were on dialysis for more than 8
      months. Patients on hemodialysis had a poorer QOL as compared to their caregivers
      in all domains except for domain 4 (environment). There was no difference in the
      QOL between the three dialysis centers of the study, except for domain 3 (social
      relationship) of the patients at Mayo Hospital (a public hospital), which was
      significantly better. Nondiabetic patients had a better QOL in domain 1 (physical
      health) as compared to diabetic patients. Duration of dialysis had a reverse
      correlation with the overall QOL. CONCLUSIONS. We found that QOL of hemodialysis
      patients was poor as compared to caregivers of the patients, especially that of
      diabetics. Also, duration of dialysis had a reverse correlation with QOL.

PMID- 21189428
TI  - Drinking water composition and incidence of urinary calculus: introducing a new
      index.
AB  - INTRODUCTION. We searched for a pathophysiologically based feature of major water
      electrolytes, which may define water quality better than the water hardness,
      respecting urinary calculus formation. MATERIALS AND METHODS. Utilizing a
      multistage stratified sampling, 2310 patients were diagnosed in the imaging
      centers of the provincial capitals in Iran between 2007 and 2008. These were
      composed of 1755 patients who were settled residents of 24 provincial capitals.
      Data on the regional drinking water composition, obtained from an accredited
      registry, and their relationships with the region's incidence of urinary calculi
      were evaluated by metaregression models. The stone risk index (defined as the
      ratio of calcium to magnesium-bicarbonate product in drinking water) was used to
      assess the risk of calculus formation. RESULTS. No correlation was found between
      the urinary calculus incidence and the amount of calcium, bicarbonate, or the
      total hardness of the drinking water. In contrast, water magnesium had a
      marginally significant nonlinear inverse relationship with the incidence of the
      disease in the capitals (R(2) = 26%, P = .05 for a power model). The stone risk
      index was associated nonlinearly with the calculus incidence (R(2) = 28.4%, P =
      .04). CONCLUSIONS. Urinary calculus incidence was inversely related with drinking
      water magnesium content. We introduced a new index constructed on the foundation
      of a pathophysiologically based formula; the stone risk index had a strong
      positive association with calculus incidence. This index can have therapeutic and
      preventive applications, yet to be confirmed by clinical trials.

PMID- 21189429
TI  - Hyperuricemia and albuminuria in patients with type 2 diabetes mellitus.
AB  - INTRODUCTION. Hyperuricemia is an independent risk factor for kidney dysfunction
      in diabetic patients. On the other hand, albuminuria is considered as the proxy
      of early stages of diabetic nephropathy. We investigated the correlation between
      hyperuricemia and albuminuria in patients with diabetes mellitus. MATERIALS AND
      METHODS. In a cross-sectional study of 1275 patients (555 men and 720 women) with
      type 2 diabetes mellitus, serum uric acid and urinary albumin-creatinine ratio
      were determined. Other metabolic parameters including lipid profile, hemoglobin
      A1c, glomerular filtration rate, body mass index, blood pressure, blood glucose
      were assessed, as well. RESULTS. The mean age of the patients was 52.45 +/- 10.11
      years old. Serum uric acid levels for normoalbuminuric, microalbuminuric, and
      macroalbuminuric patients were 4.49 +/- 1.22 mg/dL, 4.84 +/- 1.52 mg/dL, and 6.15
      +/- 1.68 mg/dL, respectively. Among patients with clinical metabolic syndrome,
      233 (27.5%) were in the forth upper quartile of uric acid level (> 5.3 mg/dL),
      but in diabetic patients without this syndrome, only 80 (18.7%) were in this
      group. There was a significant relationship between hyperuricemia and serum
      triglyceride, fasting blood glucose, hemoglobin A1c, glomerular filtration rate,
      and serum creatinine levels (P < .001). No significant correlation was found
      between hyperuricemia and cholesterol levels, age, duration of diabetes mellitus,
      and body mass index. Serum uric acid level correlated positively with urinary
      albumin-creatinine ratio (P = .04). CONCLUSIONS. We showed that higher serum uric
      acid concentrations were associated with a greater probability of albuminuria in
      patients with type 2 diabetes mellitus.

PMID- 21189430
TI  - Outcomes of fasciotomy in patients with crush-induced acute kidney injury after
      Bam earthquake.
AB  - INTRODUCTION. Fasciotomy may increase the morbidity and mortality in patients
      with crush-induced acute kidney injury (AKI), by creating an open wound,
      increasing the risk of bleeding, coagulopathy, and potentially fatal sepsis. This
      study evaluates the outcomes of fasciotomy in these patients after Bam earthquake
      in Iran. MATERIALS AND METHODS. We reviewed medical records of victims of Bam
      earthquake complicated with crush-induced AKI. Demographic, biochemical, and
      clinical data of patients who underwent fasciotomy were evaluated and compared
      with other patients with AKI. RESULTS. Fasciotomy was performed for 70 of 200
      patients with crush-induced AKI (35.0%). There were no significant differences
      regarding sex, age, time under the rubble, and muscle enzymes level between these
      patients and those without fasciotomy. They did not experience higher rates of
      disseminated intravascular coagulopathy, sepsis, adult respiratory distress
      syndrome, amputation, and dialysis session. Neither did they have a longer
      hospitalization period or higher death rate. CONCLUSIONS. This study showed that
      fasciotomy did not have any deteriorating effect on morbidity and mortality of
      patients with crush-induced AKI after Bam earthquake.

PMID- 21189431
TI  - Effect of hydroxymethylglutaryl-CoA reductase inhibitors on low-density
      lipoprotein cholesterol, interleukin-6, and high-sensitivity C-reactive protein
      in end-stage renal disease.
AB  - INTRODUCTION. This study was conducted to determine the effect of statins on the
      serum levels of interleukin-6 (IL-6), low-density lipoprotein cholesterol (LDLC),
      and high-sensitivity C-reactive protein (HSCPR). MATERIALS AND METHODS. This
      randomized clinical trial was carried out on 95 hemodialysis patients divided
      into three groups of atorvastatin, 10 mg; simvastatin, 20 mg; and lovastatin, 40
      mg, daily, administered for 2 months. Levels of serum HSCRP, IL-6, and LDLC were
      all measured before and after the study period. RESULTS. At baseline, 59% of the
      hemodialysis patients presented with elevated HSCRP, 46.3% them had increased IL
      6, and 26.3% had an increased LDLC level. The three drugs were capable to lower
      the level of HSCRP, among which atorvastatin had the highest effect size (41.8%
      reduction, P = .001). Lovastatin stood in the next (37.6% reduction, P = .02),
      while HSCRP reduction was not significant in the simvastatin group (25%
      reduction, P = .14). Neither of the drugs significantly reduced IL-6 levels.
      Effects of atorvastatin and simvastatin on the LDLC levels were significant,
      while lovastatin had a marginal effect. CONCLUSIONS. Use of statins resulted in
      CRP reduction in patients on hemodialysis. Atorvastatin was much more effective
      than lovastatin, while CRP reduction was not significant by simvastatin. However,
      simvastatin had the greatest impact on LDLC. None of these drugs could reduce IL
      6 levels within 2 months.

PMID- 21189432
TI  - Vascular access and survival in hemodialysis patients in Rasht, Iran.
AB  - INTRODUCTION. Arteriovenous fistulas and grafts are two common permanent access
      methods for hemodialysis. Selection of an appropriate access, appropriate
      surgical techniques, and treatment of complications are basic principles of long
      term maintenance of vascular access. We aimed to assess the survival of
      arteriovenous fistulas and grafts in our dialysis center. MATERIALS AND METHODS.
      A total of 200 cases of vascular access placement in 155 patients were reviewed.
      Data on the type of access and the duration of a functional access were collected
      for survival analysis. RESULTS. The median duration of dialysis was 70.6 months.
      Among different methods of vascular access, elbows' wrinkle arteriovenous
      fistulas (57.0%) were the most frequently used vascular access. The longest mean
      survival period based on the anatomical location was seen in patients with the
      arteriovenous fistulas of the wrist (100.2 months); however, there were no
      significant relationships between anatomical location and durability of vascular
      access. The mean survival of vascular access was 96.4 months in men and 104.9
      months in women. The mean vascular access survival in diabetic patients was 78.8
      months as compared with 101.6 months in nondiabetics. CONCLUSIONS. Antecubital
      arteriovenous fistulas were the most common forms of vascular access among our
      hemodialysis patients; however, arteriovenous fistulas of the wrist provided a
      better survival. Monitoring of the arteriovenous access and early diagnosis of
      its insufficiency can guarantee timely intervention and a better survival time.

PMID- 21189433
TI  - Serum triiodothyronine level as an indicator of inflammation in patients
      undergoing dialysis.
AB  - INTRODUCTION. It has been shown that inflammation affects thyroid function. In
      patients with end-stage renal disease, low plasma triiodothyronine (T3) may be an
      unsuspected expression of the inflammatory state of these patients. This study
      evaluated the correlation between T3 and high-sensitivity C-reactive protein
      (HSCRP) levels in patients on peritoneal dialysis (PD) and hemodialysis.
      MATERIALS AND METHODS. This is a cross-sectional study aiming at the correlation
      between T3 and HSCRP levels among 30 patients on PD, 30 patients on hemodialysis,
      and 20 healthy individuals. Serum levels of HSCRP, T3, thyroxine (T4), thyroid
      stimulating hormone, T3 resin uptake, and free T3 index (FT3I) and free T4 index
      (FT4I) were compared between the three groups. RESULTS. There were no significant
      differences between hemodialysis and PD patients in respect to T3, T4, FT3I, and
      FT4I. In PD and hemodialysis patients, T3 and FT3I were lower than in controls (P
      < .001), but there was no significant difference between PD and hemodialysis
      patients. T3 resin uptake and thyroid stimulating hormone differed significantly
      between PD and hemodialysis patients. There was a significant inverse correlation
      between HSCRP and T3 and FT3I among hemodialysis patients (P = .04); however,
      there was no such correlations in PD patients. CONCLUSIONS. The relationship
      between T3 and HSCRP suggests that inflammation might be involved in the low T3
      syndrome in hemodialysis patients, but we did not find a significant correlation
      between T3 and HSCRP levels in patients on peritoneal dialysis.

PMID- 21189434
TI  - Comparison of oral folic acid and folinic acid on blood homocysteine level of
      patients on hemodialysis.
AB  - INTRODUCTION. Hyperhomocysteinemia is common in patients with chronic kidney
      disease. There is a direct relationship between cardiovascular mortality and
      increase of blood homocysteine. Folic acid is used as common treatment in such
      patients. Folinic acid, a shortened form of folic acid, is not affected by
      inhibitors of dihydrofolate reductase enzyme such as methoterxate. This study was
      performed to evaluate the effect of oral folinic acid on the blood homocysteine
      level of hemodialysis patients, in comparison with folic acid. MATERIALS AND
      METHODS. This clinical trial was performed on 60 hemodialysis patients. The
      participants were divided into 2 groups to receive either 15 mg of oral folic
      acid or 15 mg of oral folinic acid, daily. Blood homocysteine levels were
      measured before dialysis and after the study period. RESULTS. Folic acid and
      folinic acid decreased the blood homocysteine levels by 33.0% and 28.7%,
      respectively (P < .001). However, only 3 patients (6.5%) enjoyed a normalized
      homocysteine level. CONCLUSIONS. Our study showed that both folic and folinic
      acid decreased the blood homocysteine level and no meaningful difference was
      observed between them; therefore, we suggest they can be used interchangeably.

PMID- 21189435
TI  - Pyuria as a screening test for detection of urinary tract infection in patients
      on long-term hemodialysis.
AB  - INTRODUCTION. This study was conducted to evaluate the sensitivity and
      specificity of pyuria detection in centrifuged urine samples of patients on
      hemodialysis, and its relationship with urinary tract infection. MATERIALS AND
      METHODS. Clean-catch midstream urine samples of 90 hemodialysis patients (34
      women and 56 men) were obtained and divided into two parts for examination of
      urine sediment and urine culture. Pyuria was defined as the presence of more than
      10 leukocytes per high-power field of microscope. RESULTS. Ninety patients with a
      mean age of 52.8 +/- 14.2 and a mean period of dialysis of 3.3 +/- 2.3 years were
      studied. Forty-five participants had pyuria and only 16 (35.5%) of them had a
      positive urine culture for infection. Pyuria and urinary tract infection were
      present in 52.9% and 29.4% of the women and 48.2% and 10.7% of the men,
      respectively. The sensitivity and specificity of pyuria screening for urinary
      tract infection was 100% and 61.8%, respectively. The positive and negative
      predictive values were 35.5% and 100%, respectively. CONCLUSIONS. In patients on
      hemodialysis, because of the low specificity and positive predictive values,
      samples with positive pyuria should be cultured to confirm urinary tract
      infections.

PMID- 21189436
TI  - Outcomes of kidney transplantation in patients with systemic lupus erythematosus:
      a single-center study.
AB  - INTRODUCTION. This study aimed to compare outcomes of kidney transplantation in
      patients with systemic lupus erythematosus (SLE) and a matched control group of
      non-SLE kidney recipients. MATERIALS AND METHODS. In a case-control study, 33
      patients with kidney transplantation due to end-stage renal disease caused by SLE
      were matched to a control group consisted of 33 non-SLE patients who had been
      transplanted during the same period of time in our center. The clinical
      characteristics, complications, and patient and graft survival were compared
      between the two groups. RESULTS. In each group, 12 patients (36.4%) received a
      kidney from a deceased donor, 15 (45.4%) from a living unrelated donor, and 6
      (18.2%) from a living related donor. There was no significant difference between
      the outcome in SLE patients and duration of dialysis before transplantation. The
      mean duration of hospital stay was 23.4 +/- 18.1 days in the SLE group, while it
      was 13.0 +/- 7.3 days in the controls (P = .006). One-year graft survival was
      79.0% in patients with SLE and 90.9% in non-SLE patients (P = .17). One-year
      patient survival was 93.9% in patients with SLE versus 81.8% in the controls (P =
      .26). Nine patients in the SLE group versus 11 patients in the control group
      developed posttransplant complications (P = .59). CONCLUSIONS. Although hospital
      stay after transplantation was longer in the SLE kidney recipients than controls,
      safety of kidney transplantation was comparable. Graft failure in the SLE
      patients was not significantly different between patients with different sources
      of kidneys.

PMID- 21189437
TI  - 25-hydroxyvitamin D deficiency in kidney transplant recipients.
AB  - INTRODUCTION. After kidney transplantation, patients appear to have vitamin D
      deficiency due to the use of immunosuppressive treatment and prevention of
      sunlight. This study was designed to determine vitamin D serum levels in kidney
      transplant patients in comparison with healthy individuals. MATERIALS AND
      METHODS. Forty-six kidney transplant patients with a creatinine clearance greater
      than 60 mL/min and 46 healthy individuals with normal kidney function were tested
      for serum levels of calcium, phosphorus, 25-hydroxyvitamin D, and parathyroid
      hormone at the end of the summer. RESULTS. Thirty-one participants were men and
      15 were women in each group. The mean age was 41.0 +/- 14.2 years in kidney
      transplant recipients and 41.4 +/- 13.7 years in the control group. Inadequate
      serum 25-hydroxyvitamin D was seen in 93.5% of the transplant patients and in
      89.1% of the controls. There was a 26.1% [corrected] vitamin D insufficiency (20
      ng/mL to 30 ng/mL) and a 67.4% [corrected] deficiency (lower than 20 ng/mL) in
      the patients, and these rates were 21.7% [corrected] and 67.4% [corrected] in the
      control group, respectively. There was no significant difference between the two
      groups. CONCLUSIONS. Vitamin D deficiency is prevalent in kidney transplant
      patients. Lack of a significant difference between our two groups may be
      attributable to the high prevalence of vitamin D deficiency in general population
      and the use of vitamin D supplementation in transplant patients. Indeed, adequate
      doses of vitamin D in these patients are undetermined. They may need higher doses
      for normalization of serum vitamin D and metabolic requirements.

PMID- 21189438
TI  - Membranoproliferative glomerulonephritis in a postpartum woman with sickle cell
      disease.
AB  - Renal insufficiency occurs in a considerable proportion of patients with sickle
      cell disease. Common advanced glomerular lesions include focal segmental
      glomerulosclerosis and nonimmune membranoproliferative glomerulonephritis. Due to
      the paucity of data supporting an immune-mediated pathophysiology, anti
      inflammatory and immunosuppressive therapies have not been successfully evaluated
      in such patients. We present a case of membranoproliferative glomerulonephritis
      in a postpartum patient with sickle cell disease, where treatment with steroids
      was helpful.

PMID- 21189439
TI  - Tubulointerstitial nephritis and uveitis: report of a rare syndrome.
AB  - Tubulointerstitial nephritis and uveitis (TINU) is a rare syndrome with unknown
      pathogenesis. Data have shown a higher prevalence in female gender. We present a
      man with tubulointerstitial nephritis and uveitis syndrome and antitubular
      antibody. A 23-year-old man presented with a history of weight loss, nausea, and
      vomiting, and uveitis. His serum creatinine was 2.1mg/d with pyuria and
      proteinuria in urinalysis. Other laboratory and imaging studies were
      unremarkable. Kidney biopsy showed granulomatous interstitial nephritis. Normal
      renal tissue specimen treated with patient's serum showed focal cytoplasmic
      staining in cortical tubular cells. The patient received prednisolone for 1
      month. Interstitial nephritis and uveitis were well controlled. There was no
      recurrence in 1-year follow-up. We suggest that tubulointerstitial nephritis and
      uveitis syndrome should be considered in differential diagnosis of patients with
      interstitial nephritis and uveitis. Antitubular antibody may be used as a
      diagnosis marker for this syndrome.

PMID- 21189442
TI  - Interleukin-17A and interleukin-17F mRNA expression in peripheral blood
      mononuclear cells of patients with multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is a CD4+ T cell-mediated autoimmune disease
      affecting the central nervous system (CNS). It was previously believed that Th1
      cells were pathogenic T cells in experimental autoimmune encephalomyelitis (EAE).
      However, the functional role of Th1 cells in EAE has been reconsidered upon the
      discovery of IL-17-producing T cells which are considered as dominant effectors
      for inducing autoimmune tissue inflammation. OBJECTIVE: The objective of this
      study was to assess the role of IL-17A and IL-17F in MS pathogenesis. METHODS: We
      evaluated mRNA expression of IL-17A and IL-17F in thirty-five Iranian patients
      with relapsing-remitting MS (RRMS) and twenty-five healthy controls by
      Quantitative Real Time PCR. RESULTS: The results of this study showed a twenty
      fold increase in the expression of IL-17A mRNA in MS patients compared to the
      control group (p < 0.0001). IL-17F mRNA expression in MS patients was thirty
      three-times greater than the control group (p = 0.0008). IL-17A mRNA expression
      in the periphery was positively correlated with the expression of IL-17F
      transcripts in MS patients and controls (p < 0.01and p < 0.05, respectively).
      CONCLUSION: These results indicate the critical role of Th17- mediated cytokines
      in the development of MS which was classically considered as a Th1-mediated
      disorder. The results of this study showed, for the first time, the importance of
      IL-17F in MS immunopathogenesis.

PMID- 21189443
TI  - The effect of cationic liposomes encapsulating pcDNA3.1+PA plasmids on humoral
      immune response in mice.
AB  - BACKGROUND: DNA vaccines are third generation vaccines which have made promises
      to combat infectious diseases. Cationic liposomes are used as effective delivery
      systems for DNA vaccines to generate stronger immunity. OBJECTIVE: Encapsulation
      of pcDNA3.1+PA plasmid, encoding protective antigen (PA) of Bacillus anthracis
      (B. anthracis) into cationic liposomes, and evaluation of its effect on specific
      humoral specific immunity against PA were aimed. METHODS: The liposomes
      containing pcDNA3.1+PA plasmids were prepared with phosphatidylcholine (PC),
      dioleoyl phosphatidylethanolamine (DOPE) and 1, 2-dioleoyl-3-trimethylammonium
      propane (DOTAP) using dehydration-rehydration method. BALB/c mice were immunized
      by intramuscular (IM) injection to investigate the immunogenicity of the
      formulations. The resulting specific antibodies against PA, total IgG, IgG1,
      IgG2a and IgG2b isotypes, were evaluated by enzyme linked immunosorbent assay
      (ELISA) method. CONCLUSION: A higher concentration of specific IgG against PA was
      found in sera of a group immunized with the encapsulated plasmid compared with
      the naked plasmid alone. This difference was significant for IgG1 isotype.

PMID- 21189444
TI  - The influence of immunosuppressive drugs on vascular endothelial growth factor
      production in relation to VEGF -1154 g and -2578 C genotypes.
AB  - BACKGROUND: The pathogenesis of many diseases is correlated to irregularity in
      vascular endothelial growth factor (VEGF) expression. RESULTS from several
      association studies show that variation in the level of VEGF expression is
      related to polymorphic sequences within the VEGF gene. Additionally, there are
      many studies showing that some gene polymorphisms significantly influence the
      pharmacokinetics of immunosuppressive drugs. OBJECTIVE: The aim of this study was
      to determine the influence of immunosuppressive drugs on VEGF production in
      individuals with different VEGF genotypes. METHODS: ARMS-PCR was used to genotype
      VEGF polymorphisms at positions -1154 and -2578 within the promoter of VEGF gene.
      A VEGF-specific ELISA was used to determine the influence of immunosuppressive
      drugs on VEGF production in PBMCs of individuals with different VEGF genotypes.
      RESULTS: Suppressive effect of mycophenolic acid was observed just in individuals
      with GG -1154/CC -2578, GG -1154/CA -2578 and GA -1154/CC -2578 haplotypes.
      Additionally, VEGF was significantly suppressed in all individuals after
      treatment with rapamycin except those who had AA -1154/CA -2578 and AA -1154/AA 
      2578 VEGF genotype combinations. CONCLUSION: RESULTS of a recent study revealed
      that MMF treatment might be effective in preventing chronic renal rejection only
      in recipients with IL-10 high producer genotype. Additionally result of another
      study showed that CYP3A5 genotype markedly influences the pharmacokinetics of
      rapamycin in kidney transplant recipients. Therefore with regard to our results,
      different suppressive effect of mycophenolic acid and rapamycin on VEGF
      production might also be dependent on VEGF genotype.

PMID- 21189445
TI  - Receptor activator of nuclear factor kappa B ligand (RANKL) levels in peri
      implant crevicular fluid.
AB  - BACKGROUND: Receptor activator of nuclear factor kappa B ligand (RANKL) is one of
      the key cytokines in the induction of osteoclastogenesis both in vitro and in
      vivo. Several reports indicated the presence of sRANKL in gingival crevicular
      fluid of patients with periodontal diseases. OBJECTIVE: To determine the presence
      of RANKL in peri-implant crevicular fluid samples of implants with peri
      implantitis, peri-implant mucositis and healthy controls. METHODS: In this study,
      40 implants were categorized as clinically healthy, peri-implant mucositis and
      peri-implantitis according to the clinical and radiographic findings. Filter
      paper strips were used to collect peri-implant crevicular fluid for 30 seconds in
      the base of the crevice/pocket. Peri-implant crevicular fluid (PICF) samples were
      obtained from buccal and lingual aspects of implants. Plaque index, probing
      depth, gingival index and bleeding on probing were recorded at six sites per
      implant. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the
      PICF levels of sRANKL. RESULTS: There were no statistically significant
      differences in sRANKL concentration between healthy group, peri-implant mucositis
      and periimplantitis (p=0.12). There were also no statistical correlation between
      the concentration of sRANKL and probing pocket depth (R=0.051, p=0.65), or any of
      the other clinical regarding (p>0.05). No differences between the mean sRANKL
      concentration in the buccal and lingual sites were found (p=0.693). CONCLUSION:
      Our results may suggest that peri-implant crevicular fluid analysis of sRANKL in
      conjunction with some other osteoclastogenic mediators could be further
      investigated in further well-designed prospective longitudinal studies on a
      larger-scale sample size in the evaluation of dental implants.

PMID- 21189446
TI  - Hypersensitivity to house dust mite and cockroach is the most common allergy in
      north of iran.
AB  - BACKGROUND: Asthma and allergic rhinitis are among the most common diseases in
      the world. OBJECTIVE: The aim of this study was to detect, by skin prick test,
      aeroallergens in allergic patients in Sari, Mazandaran in north of Iran. METHODS:
      This is a prospective study of skin prick test of aeroallergens in asthma,
      allergic rhinitis and their combination with clinical diagnosis. Three hundred
      and seventy five cases aged between 5 to 50 years, were referred to Tooba and Boo
      Ali allergic centers of Mazandaran University of Medical Sciences between
      December 2006 and July 2009. The aeroallergens studied included house dust mites
      (Dermatophagoides farinae, Dermatophagoides pteronyssinus), cockroaches, feather,
      aspergillus, Alternaria, pigweed, nettle, oak and maple. RESULTS: Of the studied
      individuals, 175 cases were males (46.7%) and 200 were females (53.3%), of which
      156 (n=41.5%) reacted to allergen extracts. In asthma, allergic rhinitis and
      their combination, the respective positive percentages were 26.6%, 22.9%, and
      32.6% for Dermatophagoides farinae; 26.6%, 25.3%, and 23.3% for Dermatophagoides
      pteronyssinus; 12.7%, 17.4%, and 11.6% for cockroaches and 16.5%, 4.7%, and 7.0%
      for the feather. Other allergens were positive up to 5 percent. Total IgE levels
      were elevated in 56.4%, 53% and 60.5% of asthmatic, allergic rhinitis and the
      combination group, respectively. Eosinophils count was elevated in 40.5%, 33.2%
      and 37.2% of the same groups, respectively. CONCLUSION: The hypersensitivity to
      house dust mites is very common in north of Iran which may be attributed to the
      warm and humid weather of this area.

PMID- 21189447
TI  - Level of interferon gamma in the blood of tuberculosis patients.
AB  - BACKGROUND: Interferon gamma (IFN-gamma), a cytokine produced by a variety of
      cells is involved in the immune response against M. tuberculosis. It activates
      the production of other cytokines and molecules that kill mycobacterium. IFN
      gamma also has diagnostic role in identification of active and latent
      tuberculosis. OBJECTIVE: To determine the level of IFN-gamma in the blood of TB
      patients. METHODS: Ninety-one subjects were selected, including 54 active TB
      patients and 37 healthy controls. Among 54 TB patients, 27 had confirmed TB and
      27 were. Clinically diagnosed as having TB. IFN-gamma concentration was
      determined in their blood by an ELISA technique. RESULTS: In TB patients, Mean +
      SD of IFN-gamma was 48.69 + 28.78 pg/ml while it was 12.99 + 5.70 pg/ml in the
      control group (p <0.001). Significant differences in the level of IFN-gamma were
      observed among confirmed TB patients, clinically diagnosed TB patients and the
      control group (Mean + SD 59.68 + 28.78, 36.85 + 24.76 and 12.99 + 5.70 pg/ml,
      respectively). Furthermore, a significant negative correlation was observed
      between the concentration of IFN-gamma in TB patients and the duration of anti
      tuberculosis therapy. CONCLUSION: IFN-gamma level was high in both clinically
      diagnosed and confirmed TB patients as compared to a control group. Measurement
      of IFN-gamma production is helpful to diagnose active tuberculosis, but further
      research is required.

PMID- 21189448
TI  - Effect of captopril on TNF-alpha and IL-10 in the livers of bile duct ligated
      rats.
AB  - BACKGROUND: The renin-angiotensin system has an important role in hepatic
      inflammation and fibrosis. Renin-angiotensin system blockade by angiotensin
      converting enzyme (ACE) inhibitors provides some protective effects against
      hepatic fibrogenesis. Captopril as an ACE inhibitor can decrease inflammatory
      mediators and attenuate hepatic fibrosis in the livers of bile duct ligated (BDL)
      rats. OBJECTIVE: The present study was conducted to investigate the effects of
      captopril on cytokine production in hepatic fibrosis induced by a bile duct
      ligation model in rats. METHODS: Male rats were divided into four groups
      including; control, sham operated, BDL, and BDL plus captopril (10 mg/kg/day,
      orally). After 28 days of treatment, the livers were removed for cytokine
      analysis. Hepatic interleukin (IL)-10 and tumor necrosis factor (TNF)-alpha
      levels were measured. RESULTS: Captopril treatment decreased the hepatic content
      of the proinflammatory cytokine TNF-alpha and increased the anti-inflammatory
      cytokine IL-10. CONCLUSION: the present study suggests that the protective effect
      of captopril on hepatic fibrosis is likely to be mediated by cytokine production.

PMID- 21189449
TI  - Human leukocyte antigen B27 in 453 Asian Indian patients with seronegative
      spondyloarthropathy.
AB  - BACKGROUND: Spondyloarthropathies are a group of closely related inflammatory
      arthritis which involve the axial skeleton and are negative for rheumatoid
      factor. OBJECTIVE: This case-control study was conducted to examine HLA- B27
      positivity in patients with seronegative spondyloarthritis (SSA) as per ESSG
      criteria and compare the frequency with healthy controls because a lower
      positivity is reported in Indians. METHOD: The study included 453 patients and
      200 controls. HLA -B27 typing was done by microlymphocytotoxicity and/or by
      sequence specific primers (SSP) using commercial kits. Patients were categorised
      as Ankylosing Spondylitis (AS), Undifferentiated Spondyloarthropathy, SSA with
      inflammatory bowel disease, reactive arthritis, psoriatic arthritis and juvenile
      spondyloarthropathy. RESULTS: HLA- B27 antigen was present in 56% of patient and
      3.5% controls with highest frequency in juvenile spondyloarthropathy (80%),
      followed by AS (76%). The P value < 0.001 for all categories of SSA and overall
      Odds ratio was 34.9. CONCLUSION: This study showed HLA-B27 frequency slightly
      lower than reported in Caucasian SSA patients and in our opinion HLA- B27 testing
      is extremely useful in young patients with suspected SSA.

PMID- 21189450
TI  - Chimeric p53 as an alternative therapy for hypoxic tumors.

PMID- 21189451
TI  - Microvilli expressed on glioma cells keep cytotoxic cells at a distance.
AB  - Glioblastoma multiforme (GBM), the most frequent primary brain tumor in adults,
      carries a particularly poor prognosis despite aggressive treatment approaches. A
      possible explanation for treatment failure resides in the capacity of glioma
      cells to infiltrate the brain parenchyma and therefore escape surgical removal
      and radiation exposure. One of the most promising novel strategies in glioma
      therapy is to use the patient's immune system to attack the tumor. Cytotoxic
      effector cells are crucial components of the immune system to fight cancers;
      genetically modified cytotoxic T cells that recognize tumor antigens can destroy
      cancer cells. Glioma cells, on the other hand, use several strategies to escape
      this immunological attack. In a recent study, Hoa and colleagues reported that
      cell surface expression of microvilli protects gliomas from being killed by
      cytotoxic effector cells.

PMID- 21189452
TI  - Function of a retrotransposon nucleocapsid protein.
AB  - Long terminal repeat (LTR) retrotransposons are not only the ancient predecessors
      of retroviruses, but they constitute significant fractions of the genomes of many
      eukaryotic species. Studies of their structure and function are motivated by
      opportunities to gain insight into common functions of retroviruses and
      retrotransposons, diverse mechanisms of intracellular genomic mobility, and host
      factors that diminish or enhance retrotransposition. This review focuses on the
      nucleocapsid (NC) protein of a Saccharomyces cerevisiae LTR retrotransposon, the
      metavirus, Ty3. Retrovirus NC promotes genomic (g)RNA dimerization and packaging,
      tRNA primer annealing, reverse transcription strand transfers, and host protein
      interactions with gRNA. Studies of Ty3 NC have revealed key roles for Ty3 NC in
      formation of retroelement assembly sites (retrosomes), and in chaperoning primer
      tRNA to both dimerize and circularize Ty3 gRNA. We speculate that Ty3 NC,
      together with P-body and stress-granule proteins, plays a role in transitioning
      Ty3 RNA from translation template to gRNA, and that interactions between the
      acidic spacer domain of Ty3 Gag3 and the adjacent basic NC domain control
      condensation of the virus-like particle.

PMID- 21189455
TI  - Evaluation of kV cone-beam ct performance for prostate IGRT: a comparison of
      automatic grey-value alignment to implanted fiducial-marker alignment.
AB  - PURPOSE: Cone-beam computed tomography (CBCT) is a new image-guided radiation
      therapy (IGRT) technique for patient alignment in radiotherapy. The CBCT x-ray
      volume imaging system from Elekta allows for a variety of alignment methods. The
      aim of this study is to assess the accuracy of soft-tissue-based automatic
      alignment as compared with manual alignment using intraprostatic fiducials.
      METHODS AND MATERIALS: All patients were treated on an Elekta Synergy S linear
      accelerator with kilovoltage CBCT. All alignments were performed using the x-ray
      volume imaging system and associated software. Automatic alignment with gray
      value-based registration and manual alignment to fiducial markers were performed.
      Transitional corrections along each axis as well as 3-dimensional vectors were
      compared with evaluate the accuracy of gray-value-based registration compared
      with fiducials. RESULTS: The distribution of the 3-dimensional vectors between
      gray-value and fiducial registrations demonstrated notable differences. The mean
      summed vector was 0.75 cm, with a standard deviation (SD) of 0.52 cm and range
      from 0.04 to 2.06 cm. There was minimal difference along the lateral direction,
      with a mean +/- SD of -0.02 cm +/- 0.13 cm. However, there were large
      discrepancies along the superior-inferior and anterior-posterior direction
      alignments, with mean +/- SD values of -0.55 +/- 0.48 cm and -0.31 +/- 0.43 cm,
      respectively. CONCLUSIONS: CBCT with soft-tissue-based automatic corrections is
      not an accurate alignment compared with manual alignment to fiducial markers for
      prostate IGRT. We have concluded that a daily manual alignment to fiducials is
      one of the most reliable methods to maintain accuracy in prostate IGRT.

PMID- 21189456
TI  - Effect of five different stages of ripening on chemical compounds in medlar
      (Mespilus germanica L.).
AB  - The study of changes of nutritional value of fruit during the ripening process
      can help estimate the optimal date for fruit harvesting to achieve the best
      quality for direct consumption and further utilization. The aim of this study was
      to monitor the changes of chemical composition of medlar fruit (Mespilus
      germanica L.) measured at five various ripening stages including 134, 144, 154,
      164 and 174 days after full bloom (DAFB). Fruits were analyzed and ascorbic acid
      (AA) and total phenolic compound content with respect to the total antioxidant
      activity were determined. In addition, selected micronutrients and macronutrients
      were monitored. The results of our experiments demonstrate that ascorbic acid,
      total phenolic compound content and total antioxidant activity decreased
      significantly with increasing time of ripeness. The decreasing tendency in
      potassium, calcium and magnesium contents during the ripening stages was also
      determined. During the ripening period, the content of all micronutrients as well
      as phosphorus and sodium was balanced, with no statistically significant
      differences between the monitored ripening stages, which can be considered as a
      positive fact with respect to ideal consumption quality of fruit.

PMID- 21189453
TI  - Selective autophagy mediated by autophagic adapter proteins.
AB  - Mounting evidence suggests that autophagy is a more selective process than
      originally anticipated. The discovery and characterization of autophagic
      adapters, like p62 and NBR1, has provided mechanistic insight into this process.
      p62 and NBR1 are both selectively degraded by autophagy and able to act as cargo
      receptors for degradation of ubiquitinated substrates. A direct interaction
      between these autophagic adapters and the autophagosomal marker protein LC3,
      mediated by a so-called LIR (LC3-interacting region) motif, their inherent
      ability to polymerize or aggregate as well as their ability to specifically
      recognize substrates are required for efficient selective autophagy. These three
      required features of autophagic cargo receptors are evolutionarily conserved and
      also employed in the yeast cytoplasm-to-vacuole targeting (Cvt) pathway and in
      the degradation of P granules in C. elegans. Here, we review the mechanistic
      basis of selective autophagy in mammalian cells discussing the degradation of
      misfolded proteins, p62 bodies, aggresomes, mitochondria and invading bacteria.
      The emerging picture of selective autophagy affecting the regulation of cell
      signaling with consequences for oxidative stress responses, tumorigenesis and
      innate immunity is also addressed.

PMID- 21189457
TI  - Synthesis of substituted 1,4-diazepines and 1,5-benzodiazepines using an
      efficient heteropolyacid-catalyzed procedure.
AB  - An efficient and improved procedure for the synthesis of 1,4-diazepine and 1,5
      benzodiazepine derivatives via the reaction of ketimine intermediates with
      aldehydes in the presence of Keggin-type heteropolyacids (HPAs) was developed.
      High yields and short reaction times were obtained for both electron-releasing
      and electron-withdrawing substituted 1,4-diazepine  and 1,5-benzodiazepines
      derivatives.

PMID- 21189458
TI  - Synthesis of a dehydroabietyl derivative bearing a 2-(2'
      hydroxyphenyl)benzimidazole unit and its selective Cu2+ chemosensing.
AB  - A dehydroabietyl derivative 2 bearing a 2-(2'-hydroxyphenyl)benzimidazole unit
      was synthesized and its sensing behaviors toward metal ions were investigated by
      UV-Vis and fluorescence spectroscopy methods. In THF solution, compound 2
      exhibited excellent selectivity for CuII over miscellaneous other metal ions
      including CrII, MnII, CoII, NiII, ZnII, CdII, AlIII, MgII, PbII, HgII, NaI, LiI
      and KI evidenced through the quenching of the fluorescence of the benzimidazole
      fragment. The reaction between 2 and Cu2+ was found to be stoichiometric with the
      formation of a 1:1 complex.

PMID- 21189459
TI  - Antimalarial activity of methanolic leaf extract of Piper betle L.
AB  - The need for new compounds active against malaria parasites is made more urgent
      by the rapid spread of drug-resistance to available antimalarial drugs. The crude
      methanol extract of Piper betle leaves (50-400 mg/kg) was investigated for its
      antimalarial activity against Plasmodium berghei (NK65) during early and
      established infections. The phytochemical and antioxidant potentials of the crude
      extract were evaluated to elucidate the possibilities of its antimalarial
      effects. The safety of the extract was also investigated in ICR mice of both
      sexes by the acute oral toxicity limit test. The leaf extract demonstrated
      significant (P < 0.05) schizonticidal activity in all three antimalarial
      evaluation models. Phytochemical screening showed that the leaf extract contains
      some vital antiplasmodial chemical constituents. The extract also exhibited a
      potent ability to scavenge the free radicals. The results of acute toxicity
      showed that the methanol extract of Piper betle leaves is toxicologically safe by
      oral administration. The results suggest that the Malaysian folklorical medicinal
      application of the extract of Piper betle leaf has a pharmacological basis.

PMID- 21189460
TI  - Solid-state [2+2] photodimerization and photopolymerization of alpha,omega
      diarylpolyene monomers: effective utilization of noncovalent intermolecular
      interactions in crystals.
AB  - [2+2] Photocycloaddition of olefins is a very useful reaction in synthetic
      organic chemistry to obtain cyclobutane-containing molecules, which are almost
      inaccessible by other methods. The reaction, when performed in the crystalline
      state, occurs more efficiently and selectively than in homogeneous solution due
      to tight and regular molecular arrangement in the crystal state. Despite numerous
      examples for the solid-state [2+2] photodimerization of monoenes, however, it is
      still a challenge to prepare not only dimers but also higher oligomers and
      polymers from conjugated polyenes, which have multiple reactive double bonds in a
      molecule. In our recent studies of the solid-state photoreactions of alpha,omega
      diarylpolyenes, noncovalent intermolecular interactions in crystals were
      effectively utilized to prealign molecules in stacking arrangements, suitable for
      the [2+2] reaction. With appropriate ring-substituents, [2+2] photodimerization
      and photopolymerization of the polyenes took place, although the degree of
      polymerization was relatively low. This review will describe the details of these
      reactions.

PMID- 21189461
TI  - Gastrointestinal Motility Monitor (GIMM).
AB  - The Gastrointestinal Motility Monitor (GIMM; Catamount Research and Development;
      St. Albans, VT) is an in vitro system that monitors propulsive motility in
      isolated segments of guinea pig distal colon. The complete system consists of a
      computer, video camera, illuminated organ bath, peristaltic and heated water bath
      circulating pumps, and custom GIMM software to record and analyze data. Compared
      with traditional methods of monitoring colonic peristalsis, the GIMM system
      allows for continuous, quantitative evaluation of motility. The guinea pig distal
      colon is bathed in warmed, oxygenated Krebs solution, and fecal pellets inserted
      in the oral end are propelled along the segment of colon at a rate of about 2
      mm/sec. Movies of the fecal pellet proceeding along the segment are captured, and
      the GIMM software can be used track the progress of the fecal pellet. Rates of
      propulsive motility can be obtained for the entire segment or for any particular
      region of interest. In addition to analysis of bolus-induced motility patterns,
      spatiotemporal maps can be constructed from captured video segments to assess
      spontaneous motor activity patterns. Applications of this system include
      pharmacological evaluation of the effects of receptor agonists and antagonists on
      propulsive motility, as well as assessment of changes that result from
      pathophysiological conditions, such as inflammation or stress. The guinea pig
      distal colon propulsive motility assay, using the GIMM system, is straightforward
      and simple to learn, and it provides a reliable and reproducible method of
      assessing propulsive motility.

PMID- 21189463
TI  - Bronchial thermoplasty: a novel therapeutic approach to severe asthma.
AB  - Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that
      delivers thermal energy to the airway wall in a precisely controlled manner to
      reduce excessive airway smooth muscle. Reducing airway smooth muscle decreases
      the ability of the airways to constrict, thereby reducing the frequency of asthma
      attacks. Bronchial thermoplasty is delivered by the Alair System and is performed
      in three outpatient procedure visits, each scheduled approximately three weeks
      apart. The first procedure treats the airways of the right lower lobe, the second
      treats the airways of the left lower lobe and the third and final procedure
      treats the airways in both upper lobes. After all three procedures are performed
      the bronchial thermoplasty treatment is complete. Bronchial thermoplasty is
      performed during bronchoscopy with the patient under moderate sedation. All
      accessible airways distal to the mainstem bronchi between 3 and 10 mm in
      diameter, with the exception of the right middle lobe, are treated under
      bronchoscopic visualization. Contiguous and non-overlapping activations of the
      device are used, moving from distal to proximal along the length of the airway,
      and systematically from airway to airway as described previously. Although
      conceptually straightforward, the actual execution of bronchial thermoplasty is
      quite intricate and procedural duration for the treatment of a single lobe is
      often substantially longer than encountered during routine bronchoscopy. As such,
      bronchial thermoplasty should be considered a complex interventional bronchoscopy
      and is intended for the experienced bronchoscopist. Optimal patient management is
      critical in any such complex and longer duration bronchoscopic procedure. This
      article discusses the importance of careful patient selection, patient
      preparation, patient management, procedure duration, postoperative care and
      follow-up to ensure that bronchial thermoplasty is performed safely. Bronchial
      thermoplasty is expected to complement asthma maintenance medications by
      providing long-lasting asthma control and improving asthma-related quality of
      life of patients with severe asthma. In addition, bronchial thermoplasty has been
      demonstrated to reduce severe exacerbations (asthma attacks) emergency rooms
      visits for respiratory symptoms, and time lost from work, school and other daily
      activities due to asthma.

PMID- 21189462
TI  - Western blotting: sample preparation to detection.
AB  - Western blotting is an analytical technique used to detect specific proteins in a
      given sample of tissue homogenate or extract. It uses gel electrophoresis to
      separate native or denatured proteins by the length of the polypeptide
      (denaturing conditions) or by the 3-D structure of the protein (native/ non
      denaturing conditions). The proteins are then transferred to a membrane
      (typically nitrocellulose or PVDF), where they are probed (detected) using
      antibodies specific to the target protein.

PMID- 21189464
TI  - Quantification of dsDNA using the Hitachi F-7000 Fluorescence Spectrophotometer
      and PicoGreen dye.
AB  - Quantification of DNA, especially in small concentrations, is an important task
      with a wide range of biological applications including standard molecular biology
      assays such as synthesis and purification of DNA, diagnostic applications such as
      quantification of DNA amplification products, and detection of DNA molecules in
      drug preparations. During this video we will demonstrate the capability of the
      Hitachi F-7000 Fluorescence Spectrophotometer equipped with a Micro Plate Reader
      accessory to perform dsDNA quantification using Molecular Probes Quant-it
      PicoGreen dye reagent kit. The F-7000 Fluorescence Spectrophotometer offers high
      sensitivity and high speed measurements. It is a highly flexible system capable
      of measuring fluorescence, luminescence, and phosphorescence. Several measuring
      modes are available, including wavelength scan, time scan, photometry and 3-D
      scan measurement. The spectrophotometer has sensitivity in the range of 50
      picomoles of fluorescein when using a 300 MUL sample volume in the microplate,
      and is capable of measuring scan speeds of 60,000 nm/minute. It also has a wide
      dynamic range of up to 5 orders of magnitude which allows for the use of
      calibration curves over a wide range of concentrations. The optical system uses
      all reflective optics for maximum energy and sensitivity. The standard wavelength
      range is 200 to 750 nm, and can be extended to 900 nm when using one of the
      optional near infrared photomultipliers. The system allows optional temperature
      control for the plate reader from 5 to 60 degrees Celsius using an optional
      external temperature controlled liquid circulator. The microplate reader allows
      for the use of 96 well microplates, and the measuring speed for 96 wells is less
      than 60 seconds when using the kinetics mode. Software controls for the F-7000
      and Microplate Reader are also highly flexible. Samples may be set in either
      column or row formats, and any combination of wells may be chosen for sample
      measurements. This allows for optimal utilization of the microplate.
      Additionally, the software allows importing micro plate sample configurations
      created in Excel and saved in comma separated values, or "csv" format. Microplate
      measuring configurations can be saved and recalled by the software for
      convenience and increased productivity. Data results can be output to a standard
      report, to Excel, or to an optional Report Generator Program.

PMID- 21189465
TI  - The NeuroStar TMS device: conducting the FDA approved protocol for treatment of
      depression.
AB  - The Neuronetics NeuroStar Transcranial Magnetic Stimulation (TMS) System is a
      class II medical device that produces brief duration, pulsed magnetic fields.
      These rapidly alternating fields induce electrical currents within localized,
      targeted regions of the cortex which are associated with various physiological
      and functional brain changes. In 2007, O'Reardon et al., utilizing the NeuroStar
      device, published the results of an industry-sponsored, multisite, randomized,
      sham-stimulation controlled clinical trial in which 301 patients with major
      depression, who had previously failed to respond to at least one adequate
      antidepressant treatment trial, underwent either active or sham TMS over the left
      dorsolateral prefrontal cortex (DLPFC). The patients, who were medication-free at
      the time of the study, received TMS five times per week over 4-6 weeks. The
      results demonstrated that a sub-population of patients (those who were relatively
      less resistant to medication, having failed not more than two good pharmacologic
      trials) showed a statistically significant improvement on the Montgomery-Asberg
      Depression Scale (MADRS), the Hamilton Depression Rating Scale (HAMD), and
      various other outcome measures. In October 2008, supported by these and other
      similar results, Neuronetics obtained the first and only Food and Drug
      Administration (FDA) approval for the clinical treatment of a specific form of
      medication-refractory depression using a TMS Therapy device (FDA approval
      K061053). In this paper, we will explore the specified FDA approved NeuroStar
      depression treatment protocol (to be administered only under prescription and by
      a licensed medical profession in either an in- or outpatient setting).

PMID- 21189466
TI  - NanoDrop microvolume quantitation of nucleic acids.
AB  - Biomolecular assays are continually being developed that use progressively
      smaller amounts of material, often precluding the use of conventional cuvette
      based instruments for nucleic acid quantitation for those that can perform
      microvolume quantitation. The NanoDrop microvolume sample retention system
      (Thermo Scientific NanoDrop Products) functions by combining fiber optic
      technology and natural surface tension properties to capture and retain minute
      amounts of sample independent of traditional containment apparatus such as
      cuvettes or capillaries. Furthermore, the system employs shorter path lengths,
      which result in a broad range of nucleic acid concentration measurements,
      essentially eliminating the need to perform dilutions. Reducing the volume of
      sample required for spectroscopic analysis also facilitates the inclusion of
      additional quality control steps throughout many molecular workflows, increasing
      efficiency and ultimately leading to greater confidence in downstream results.
      The need for high-sensitivity fluorescent analysis of limited mass has also
      emerged with recent experimental advances. Using the same microvolume sample
      retention technology, fluorescent measurements may be performed with 2 MUL of
      material, allowing fluorescent assays volume requirements to be significantly
      reduced. Such microreactions of 10 MUL or less are now possible using a dedicated
      microvolume fluorospectrometer. Two microvolume nucleic acid quantitation
      protocols will be demonstrated that use integrated sample retention systems as
      practical alternatives to traditional cuvette-based protocols. First, a direct
      A260 absorbance method using a microvolume spectrophotometer is described. This
      is followed by a demonstration of a fluorescence-based method that enables
      reduced-volume fluorescence reactions with a microvolume fluorospectrometer.
      These novel techniques enable the assessment of nucleic acid concentrations
      ranging from 1 pg/ MUL to 15,000 ng/ MUL with minimal consumption of sample.

PMID- 21189467
TI  - Closed system cell culture protocol using HYPERStack vessels with gas permeable
      material technology.
AB  - Large volume adherent cell culture is currently standardized on stacked plate
      cell growth products when microcarrier beads are not an optimal choice.
      HYPERStack vessels allow closed system scale up from the current stacked plate
      products and delivers >2.5X more cells in the same volumetric footprint. The
      HYPERStack vessels function via gas permeable material which allows gas exchange
      to occur, therefore eliminating the need for internal headspace within a vessel.
      The elimination of headspace allows the compartment where cell growth occurs to
      be minimized to reduce space, allowing more layers of cell growth surface area
      within the same volumetric footprint. For many applications such as cell therapy
      or vaccine production, a closed system is required for cell growth and
      harvesting. The HYPERStack vessel allows cell and reagent addition and removal
      via tubing from media bags or other methods. This protocol will explain the
      technology behind the gas permeable material used in the HYPERStack vessels, gas
      diffusion results to meet the metabolic needs of cells, closed system cell growth
      protocols, and various harvesting methods.

PMID- 21189468
TI  - Improved visualization and quantitative analysis of drug effects using
      micropatterned cells.
AB  - To date, most HCA (High Content Analysis) studies are carried out with adherent
      cell lines grown on a homogenous substrate in tissue-culture treated micro
      plates. Under these conditions, cells spread and divide in all directions
      resulting in an inherent variability in cell shape, morphology and behavior. The
      high cell-to-cell variance of the overall population impedes the success of HCA,
      especially for drug development. The ability of micropatterns to normalize the
      shape and internal polarity of every individual cell provides a tremendous
      opportunity for solving this critical bottleneck (1-2). To facilitate access and
      use of the micropatterning technology, CYTOO has developed a range of ready to
      use micropatterns, available in coverslip and microwell formats. In this video
      article, we provide detailed protocols of all the procedures from cell seeding on
      CYTOOchip micropatterns, drug treatment, fixation and staining to automated
      acquisition, automated image processing and final data analysis. With this
      example, we illustrate how micropatterns can facilitate cell-based assays.
      Alterations of the cell cytoskeleton are difficult to quantify in cells cultured
      on homogenous substrates, but culturing cells on micropatterns results in a
      reproducible organization of the actin meshwork due to systematic positioning of
      the cell adhesion contacts in every cell. Such normalization of the intracellular
      architecture allows quantification of even small effects on the actin
      cytoskeleton as demonstrated in these set of protocols using blebbistatin, an
      inhibitor of the actin-myosin interaction.

PMID- 21189469
TI  - Bioenergetic profile experiment using C2C12 myoblast cells.
AB  - The ability to measure cellular metabolism and understand mitochondrial
      dysfunction, has enabled scientists worldwide to advance their research in
      understanding the role of mitochondrial function in obesity, diabetes, aging,
      cancer, cardiovascular function and safety toxicity. Cellular metabolism is the
      process of substrate uptake, such as oxygen, glucose, fatty acids, and glutamine,
      and subsequent energy conversion through a series of enzymatically controlled
      oxidation and reduction reactions. These intracellular biochemical reactions
      result in the production of ATP, the release of heat and chemical byproducts,
      such as lactate and CO(2) into the extracellular environment. Valuable insight
      into the physiological state of cells, and the alteration of the state of those
      cells, can be gained through measuring the rate of oxygen consumed by the cells,
      an indicator of mitochondrial respiration--the Oxygen Consumption Rate--or OCR.
      Cells also generate ATP through glycolysis, i.e.: the conversion of glucose to
      lactate, independent of oxygen. In cultured wells, lactate is the primary source
      of protons. Measuring the lactic acid produced indirectly via protons released
      into the extracellular medium surrounding the cells, which causes acidification
      of the medium provides the Extra-Cellular Acidification Rate--or ECAR. In this
      experiment, C2C12 myoblast cells are seeded at a given density in Seahorse cell
      culture plates. The basal oxygen consumption (OCR) and extracellular
      acidification (ECAR) rates are measured to establish baseline rates. The cells
      are then metabolically perturbed by three additions of different compounds (in
      succession) that shift the bioenergetic profile of the cell. This assay is
      derived from a classic experiment to assess mitochondria and serves as a
      framework with which to build more complex experiments aimed at understanding
      both physiologic and pathophysiologic function of mitochondria and to predict the
      ability of cells to respond to stress and/or insults.

PMID- 21189470
TI  - Development of a negative selectable marker for Entamoeba histolytica.
AB  - Entamoeba histolytica is the causative agent of amebiasis and infects up to 10%
      of the world's population. The molecular techniques that have enabled the up- and
      down-regulation of gene expression rely on the transfection of stably maintained
      plasmids. While these have increased our understanding of Entamoeba virulence
      factors, the capacity to integrate exogenous DNA into genome, which would allow
      reverse genetics experiments, would be a significant advantage in the study of
      this parasite. The challenges presented by this organism include inability to
      select for homologous recombination events and difficulty to cure episomal
      plasmid DNA from transfected trophozoites. The later results in a high background
      of exogenous DNA, a major problem in the identification of trophozoites in which
      a bona fide genomic integration event has occurred. We report the development of
      a negative selection system based upon transgenic expression of a yeast cytosine
      deaminase and uracil phosphoribosyl transferase chimera (FCU1) and selection with
      prodrug 5-fluorocytosine (5-FC). The FCU1 enzyme converts non-toxic 5-FC into
      toxic 5-fluorouracil and 5-fluorouridine-5'-monophosphate. E. histolytica lines
      expressing FCU1 were found to be 30 fold more sensitive to the prodrug compared
      to the control strain.

PMID- 21189471
TI  - Profiling of methyltransferases and other S-adenosyl-L-homocysteine-binding
      Proteins by Capture Compound Mass Spectrometry (CCMS).
AB  - There is a variety of approaches to reduce the complexity of the proteome on the
      basis of functional small molecule-protein interactions such as affinity
      chromatography (1) or Activity Based Protein Profiling (2). Trifunctional Capture
      Compounds (CCs, Figure 1A) (3) are the basis for a generic approach, in which the
      initial equilibrium-driven interaction between a small molecule probe (the
      selectivity function, here S-adenosyl-(L)-homocysteine, SAH, Figure 1A) and
      target proteins is irreversibly fixed upon photo-crosslinking between an
      independent photo-activable reactivity function (here a phenylazide) of the CC
      and the surface of the target proteins. The sorting function (here biotin) serves
      to isolate the CC - protein conjugates from complex biological mixtures with the
      help of a solid phase (here streptavidin magnetic beads). Two configurations of
      the experiments are possible: "off-bead" (4) or the presently described "on-bead"
      configuration (Figure 1B). The selectivity function may be virtually any small
      molecule of interest (substrates, inhibitors, drug molecules). S-Adenosyl-(L)
      methionine (SAM, Figure 1A) is probably, second to ATP, the most widely used
      cofactor in nature (5, 6). It is used as the major methyl group donor in all
      living organisms with the chemical reaction being catalyzed by SAM-dependent
      methyltransferases (MTases), which methylate DNA (7), RNA (8), proteins (9), or
      small molecules (10). Given the crucial role of methylation reactions in diverse
      physiological scenarios (gene regulation, epigenetics, metabolism), the profiling
      of MTases can be expected to become of similar importance in functional
      proteomics as the profiling of kinases. Analytical tools for their profiling,
      however, have not been available. We recently introduced a CC with SAH as
      selectivity group to fill this technological gap (Figure 1A). SAH, the product of
      SAM after methyl transfer, is a known general MTase product inhibitor (11). For
      this reason and because the natural cofactor SAM is used by further enzymes
      transferring other parts of the cofactor or initiating radical reactions as well
      as because of its chemical instability (12), SAH is an ideal selectivity function
      for a CC to target MTases. Here, we report the utility of the SAH-CC and CCMS by
      profiling MTases and other SAH-binding proteins from the strain DH5alpha of
      Escherichia coli (E. coli), one of the best-characterized prokaryotes, which has
      served as the preferred model organism in countless biochemical, biological, and
      biotechnological studies. Photo-activated crosslinking enhances yield and
      sensitivity of the experiment, and the specificity can be readily tested for in
      competition experiments using an excess of free SAH.

PMID- 21189472
TI  - UCP1 genetic polymorphism (-3826 A/G) diminishes resting energy expenditure and
      thermoregulatory sympathetic nervous system activity in young females.
AB  - BACKGROUND: Recent findings regarding the existence of functional brown adipose
      tissue (BAT) in adult humans suggest a physiological role of BAT and uncoupling
      protein 1 (UCP1)-linked thermogenesis in energy balance. OBJECTIVE: To
      investigate whether UCP1 polymorphism was associated with resting energy
      expenditure (REE) and thermoregulatory sympathetic nervous system (SNS) activity
      in humans. METHODS: A total of 82 healthy females (20-22 years) were genotyped
      for the -3826 A/G polymorphism of the UCP1 gene using a fluorescent allele
      specific DNA primer assay system. REE was measured by indirect calorimetry. The
      thermoregulatory SNS activity was assessed by heart rate variability power
      spectral analysis according to our previously reported method. Each subject was
      studied in the morning, after an overnight fast. Nutritional values were
      calculated on the basis of 2-day food records. RESULTS: The frequencies of A/A,
      A/G and G/G genotypes were 0.27, 0.45 and 0.28, respectively. No significant
      difference was found in anthropometric indexes among the three groups. However,
      in the G/G group, the percentage of energy consumed as fat was lower (A/A: 30.7
      +/- 1.1%, A/G: 31.3 +/- 1.0%, G/G: 26.0 +/- 1.2%, P<0.01), and energy intake
      tended to be lower (A/A: 7209 +/- 310 kJ d(-1), A/G: 7075 +/- 280 kJ d(-1), G/G:
      6414 +/- 264 kJ d(-1), P=0.16). With regard to metabolic parameters, group
      differences were observed in REE (A/A: 5599 +/- 170 kJ d(-1), A/G: 5054 +/- 115
      kJ d(-1), G/G: 4919 +/- 182 kJ d(-1), P<0.01) and in thermoregulatory SNS
      activity (A/A: 313 +/- 47 ms(2), A/G: 333 +/- 42 ms(2), G/G: 185 +/- 23 ms(2),
      P<0.05). CONCLUSION: Diminished REE in G-allele carriers as well as reduced
      thermoregulatory SNS activity for the G/G genotype, suggest that attenuated UCP1
      linked thermogenesis has an adverse effect on the regulation of energy balance.

PMID- 21189474
TI  - Intradermal vaccinations with RNA coding for TAA generate CD8+ and CD4+ immune
      responses and induce clinical benefit in vaccinated patients.
AB  - The aim of this phase I/II nonrandomized trial was to assess feasibility, safety
      as well as immunological and clinical responses of a mRNA-based vaccination in
      patients with stage IV renal cell cancer using granulocyte-macrophage colony
      stimulating factor (GM-CSF) as adjuvant. Intradermal injections of in vitro
      transcribed naked mRNA, which was generated using plasmids coding for the tumor
      associated antigens mucin 1(MUC1), carcinoembryonic (CEA), human epidermal growth
      factor receptor 2 (Her-2/neu), telomerase, survivin, and melanoma-associated
      antigen 1 (MAGE-A1) were performed in 30 enrolled patients. In the first 14
      patients (cohort A) vaccinations were administered on days 0, 14, 28, and 42 (20
      ug/antigen) while in the consecutive 16 patients (cohort B) an intensified
      protocol consisting of injections at days 0-3, 7-10, 28, and 42 (50 ug/antigen)
      was used. In both cohorts, after this induction period, vaccinations were
      repeated monthly until tumor progression analyzed by Response Evaluation Criteria
      In Solid Tumors criteria (RECIST). Vaccinations were well tolerated with no
      severe side effects and induced clinical responses [six stable diseases (SD) and
      one partial response in cohort A and nine SD in cohort B]. In cohort A, 35.7%
      survived 4 years (median survival 24 months) compared to 31.25% in cohort B
      (median survival 29 months). Induction of CD4(+) and CD8(+) T cell responses was
      shown for several tumor-associated antigens (TAA) using interferon-gamma (IFN
      gamma) enzyme-linked immunosorbent spot (ELISpot) and Cr-release assays.

PMID- 21189473
TI  - Intratumoral IL-12 gene therapy results in the crosspriming of Tc1 cells reactive
      against tumor-associated stromal antigens.
AB  - HLA-A2 transgenic mice bearing established HLA-A2(neg) B16 melanomas were
      effectively treated by intratumoral (i.t.) injection of syngeneic dendritic cells
      (DCs) transduced to express high levels of interleukin (IL)-12, resulting in
      CD8(+) T cell-dependent antitumor protection. In this model, HLA-A2-restricted
      CD8(+) T cells do not directly recognize tumor cells and therapeutic benefit was
      associated with the crosspriming of HLA-A2-restricted type-1 CD8(+) T cells
      reactive against antigens expressed by stromal cells [i.e., pericytes and
      vascular endothelial cells (VEC)]. IL-12 gene therapy-induced CD8(+) T cells
      directly recognized HLA-A2(+) pericytes and VEC flow-sorted from B16 tumor
      lesions based on interferon (IFN)-gamma secretion and translocation of the lytic
      granule-associated molecule CD107 to the T cell surface after coculture with
      these target cells. In contrast, these CD8(+) T effector cells failed to
      recognize pericytes/VEC isolated from the kidneys of tumor-bearing HHD mice. The
      tumor-associated stromal antigen (TASA)-derived peptides studied are
      evolutionarily conserved and could be recognized by CD8(+) T cells harvested from
      the blood of HLA-A2(+) normal donors or melanoma patients after in vitro
      stimulation. These TASA and their derivative peptides may prove useful in vaccine
      formulations against solid cancers, as well as, in the immune monitoring of HLA
      A2(+) cancer patients receiving therapeutic interventions, such as IL-12 gene
      therapy.

PMID- 21189475
TI  - Fatal respiratory failure in a full-term newborn with two ABCA3 gene mutations: a
      case report.
AB  - Genetic mutations associated with pulmonary surfactant protein deficiency are
      associated with diverse clinical phenotypes. Mutations of the surfactant protein
      B and C genes were the first to be described. In 2004, fatal surfactant
      deficiency in newborns due to mutations of the gene encoding the adenosine
      triphosphate-binding cassette transporter A3 (ABCA3) was first reported. Few
      cases of lethal adenosine triphosphate-binding cassette transporter A3 mutations
      have been described to date. In our report, we describe a full-term newborn that
      died because of respiratory failure secondary to an uncommon ABCA3 genetic
      configuration.

PMID- 21189478
TI  - You cannot B. cereus.
AB  - This month's Genome Watch looks at the different Bacillus species that can cause
      anthrax.

PMID- 21189476
TI  - Genetic control of Candida albicans biofilm development.
AB  - Candida species cause frequent infections owing to their ability to form biofilms
      - surface-associated microbial communities - primarily on implanted medical
      devices. Increasingly, mechanistic studies have identified the gene products that
      participate directly in the development of Candida albicans biofilms, as well as
      the regulatory circuitry and networks that control their expression and activity.
      These studies have uncovered new mechanisms and signals that govern C. albicans
      biofilm development and associated drug resistance, thus providing biological
      insight and therapeutic foresight.

PMID- 21189477
TI  - Exploiting plug-and-play synthetic biology for drug discovery and production in
      microorganisms.
AB  - One of the most promising applications of synthetic biology is the biosynthesis
      of new drugs from secondary metabolites. Here, we survey a wide range of
      strategies that control the activity of biosynthetic modules in the cell in space
      and time, and illustrate how these strategies can be used to design efficient
      cellular synthetic production systems. Re-engineered versions of secondary
      metabolite biosynthetic pathways identified from any genomic sequence can then be
      inserted into these systems in a plug-and-play fashion.

PMID- 21189480
TI  - Measurement of cerebral blood flow responses to the thigh cuff maneuver: a
      comparison of TCD with a novel MRI method.
AB  - Cerebral autoregulation (CA) describes the mechanism responsible for maintaining
      cerebral blood flow (CBF) relatively constant, despite changes in mean arterial
      blood pressure (ABP). This paper introduces a novel method for assessing CA using
      magnetic resonance imaging (MRI). Images are rapidly and repeatedly acquired
      using a gradient-echo echo-planar imaging pulse sequence for a period of 4
      minutes, during which a transient decrease in ABP is induced by rapid release of
      bilateral thigh cuffs. The method was validated by comparing the observed MRI
      signal intensity change with the CBF velocity change in the middle cerebral
      arteries, as measured by transcranial Doppler (TCD) ultrasound, using a
      standardized thigh cuff maneuver in both cases. Cross-correlation analysis of the
      response profiles from the left and right hemispheres showed a greater
      consistency for MRI measures than for TCD, both for interhemisphere comparisons
      and for repeated measures. The new MRI method may provide opportunities for
      assessing regional autoregulatory changes following acute stroke, and in other
      conditions in which poor autoregulation is implicated.

PMID- 21189481
TI  - Mutation in mitochondrial ribosomal protein MRPS22 leads to Cornelia de Lange
      like phenotype, brain abnormalities and hypertrophic cardiomyopathy.
AB  - The oxidative phosphorylation (OXPHOS) system is under control of both the
      mitochondrial and the nuclear genomes; 13 subunits are synthesized by the
      mitochondrial translation machinery. We report a patient with Cornelia de Lange
      like dysmorphic features, brain abnormalities and hypertrophic cardiomyopathy,
      and studied the genetic defect responsible for the combined OXPHOS complex I, III
      and IV deficiency observed in fibroblasts. The combination of deficiencies
      suggested a primary defect associated with the synthesis of mitochondrially
      encoded OXPHOS subunits. Analysis of mitochondrial protein synthesis revealed a
      marked impairment in mitochondrial translation. Homozygosity mapping and sequence
      analysis of candidate genes revealed a homozygous mutation in MRPS22, a gene
      encoding a mitochondrial ribosomal small subunit protein. The mutation predicts a
      Leu215Pro substitution at an evolutionary conserved site. Mutations in genes
      implicated in Cornelia de Lange syndrome or copy number variations were not
      found. Transfection of patient fibroblasts, in which MRPS22 was undetectable,
      with the wild-type MRPS22 cDNA restored the amount and activity of OXPHOS complex
      IV, as well as the 12S rRNA transcript level to normal values. These findings
      demonstrate the pathogenicity of the MRPS22 mutation and stress the significance
      of mutations in nuclear genes, including genes that have no counterparts in lower
      species like bacteria and yeast, for mitochondrial translation defects.

PMID- 21189482
TI  - 18F-fluorodeoxyglucose-PET for patients with suspected spondylitis showing Modic
      change.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVE: To examine the utility of 18F
      fluorodeoxyglucose-positron emission tomography (FDG-PET) to diagnose pyogenic
      spondylitis in patients showing Modic change. SUMMARY OF BACKGROUND DATA:
      Vertebral bone marrow infection may appear as Modic type 1 signal on magnetic
      resonance imaging, so it is difficult to distinguish between common Modic change
      and infection. In the current study, we aimed to examine the utility of 18F-FDG
      PET to diagnose pyogenic spondylitis in patients showing Modic change. METHODS:
      In a prospective assessment of 312 patients showing low back pain, 18 patients
      were suspected of having pyogenic vertebral osteomyelitis because of their
      symptoms, biopsy results, blood analysis, x-ray examination, magnetic resonance
      imaging, and FDG-PET during a 1-year follow-up. RESULTS: Observers ultimately
      diagnosed 11 patients with pyogenic spondylitis (group 1 observers). FDG-PET
      evaluation by 2 radiologists (group 2 observers) showed isotope accumulation in
      the lumbar spine in 11 patients, and no accumulation in 7 patients. The
      evaluation by group 1 observers, who did not see the FDG-PET findings, was
      compared with the evaluation by group 2 observers. No patients were evaluated
      differently by group 1 and group 2 observers. CONCLUSION: In conclusion, the rate
      of detecting spondylodiscitis infection was very high if FDG-PET was additionally
      used. FDG-PET is recommended to distinguish between common Modic change and
      spinal infection.

PMID- 21189484
TI  - Fees hike leads to UK student riot.

PMID- 21189483
TI  - A comparison of HIV detection rates using routine opt-out provider-initiated HIV
      testing and counseling versus a standard of care approach in a rural African
      setting.
AB  - BACKGROUND: Routine opt-out provider-initiated HIV testing and counseling (PITC)
      remains underutilized in sub-Saharan Africa. By selectively targeting clients who
      either volunteer or have clinical indications of HIV disease, standard approaches
      to HIV counseling and testing are presumed more cost-efficient than PITC.
      METHODS: One thousand two hundred twenty-one patients aged 15- 49 years were seen
      by 22 practitioners in a mobile clinic in southern Zambia. A random sample of
      physicians was assigned to administer PITC, whereas the remaining practitioners
      offered standard non- PITC (ie, voluntary or diagnostic). Questionnaires assessed
      patient demographics and attitudes toward HIV. HIV detection rates were
      stratified by referral type, demographics, and HIV-related knowledge and
      attitudes. RESULTS: HIV prevalence was 10.6%. Infection rates detected using PITC
      [11.1%; 95% confidence interval (CI): 8.8% to 13.5%] and standard non-PITC
      (10.0%; 95% CI: 7.5% to 12.5%) did not significantly differ (odds ratio = 1.01;
      95% CI: 0.67 to 1.52; P = 0.95). Patients who did not request testing or
      demonstrate clinical indicators of HIV did not have significantly higher HIV
      prevalence than those who did (odds ratio = 0.83; 95% CI: 0.55 to 1.24; P =
      0.36). Implementation of PITC was highly acceptable and produced a 3-fold
      increase in patients tested per practitioner compared with standard non-PITC (114
      vs. 34 patients per practitioner, respectively). CONCLUSIONS: PITC detected a
      comparable HIV infection rate as a standard non-PITC approach among rural adults
      seeking primary care services. Widespread implementation of PITC may therefore
      lead to significantly more cases of HIV detected.

PMID- 21189485
TI  - Activation of P2X purinoceptors by ATP subsequent to an increase in reactive
      oxygen species causes enhanced laryngeal reflex reactivity in a rat model of
      extraoesophageal reflux.

PMID- 21189486
TI  - Chlorine disinfection of Francisella tularensis.
AB  - AIMS: To determine the range of free available chlorine (FAC) required for
      disinfection of the live vaccine strain (LVS) and wild-type strains of
      Francisella tularensis. METHODS AND RESULTS: Seven strains of planktonic F.
      tularensis were exposed to 0.5 mg.l(-1) FAC for two pH values, 7 and 8, at 5 and
      25 degrees C. LVS was inactivated 2 to 4 times more quickly than any of the wild
      type F. tularensis strains at pH 8 and 5 degrees C. CONCLUSIONS: Free available
      chlorine residual concentrations routinely maintained in drinking water
      distribution systems would require up to two hours to reduce all F. tularensis
      strains by 4 log10. LVS was inactivated most quickly of the tested strains.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This work provides contact time (CT) values
      that are useful for drinking water risk assessment and also suggests that LVS may
      not be a good surrogate in disinfection studies.

PMID- 21189487
TI  - Cool build-up to  climate conference.

PMID- 21189488
TI  - Europe's faltering biofuel aims.

PMID- 21189489
TI  - Prize for the HeLa cell story.

PMID- 21189491
TI  - Lars Chittka.

PMID- 21189490
TI  - Modified vector  attack on dengue.

PMID- 21189493
TI  - Autozygome decoded.
AB  - Consanguineous unions permit the "reunion" of ancestral chromosomal segments in a
      pattern referred to as "autozygosity," which is essentially a special form of
      homozygosity. This has long been exploited as a gene mapping tool because it is
      relatively easy to track a recessive mutation by the surrounding pattern of
      homozygous markers. The recent advent of single nucleotide polymorphism
      microarrays has rapidly replaced the historical use of microsatellites for this
      purpose. In this review, the author discusses other exciting opportunities
      offered by this unique arrangement of the human genome that range from pure
      clinical to functional genomic applications. The emerging field of whole genome
      sequencing promises to unlock much of the potential of the "autozygome."

PMID- 21189494
TI  - Extending the reach of public health genomics: what should be the agenda for
      public health in an era of genome-based and "personalized" medicine?
AB  - The decade following the completion of the Human Genome Project has been marked
      by divergent claims about the utility of genomics for improving population
      health. On the one hand, genomics is viewed as the harbinger of a brave new world
      in which novel treatments rectify known causes of disease. On the other hand,
      genomics may have little practical relevance to the principal causes or remedies
      of diseases which are predominantly social or environmental in origin,
      particularly in low- and middle-income countries. Those supportive of a role for
      public health genomics argue that increasing knowledge of genomics and molecular
      pathology could unlock effective diagnostic techniques and treatments, and better
      target public health interventions. To resolve some of these tensions, an
      international multidisciplinary meeting was held in May 2010 in Ickworth, United
      Kingdom, with the aim of setting an agenda for the development of public health
      in an era of genome-based and "personalized" medicine. A number of key themes
      emerged, suggesting a need to reconfigure both the focus for existing genomic
      research and the stage at which funding is targeted, so that priority is given to
      areas of greatest potential health impact and that translation from basic science
      to implementation is given greater emphasis. To support these developments, there
      should be an immediate, sustained and systematic effort to provide an evidence
      base. These deliberations formed the basis for six key recommendations, which
      could guide the practice of public health in an era of genomics and personalized
      medicine.

PMID- 21189495
TI  - Lifeblood of the NHS. Forword.

PMID- 21189492
TI  - The genetics and clinical manifestations of telomere  biology disorders.
AB  - Telomere biology disorders are a complex set of illnesses defined by the presence
      of very short telomeres. Individuals with classic dyskeratosis congenita have the
      most severe phenotype, characterized by the triad of nail dystrophy, abnormal
      skin pigmentation, and oral leukoplakia. More significantly, these individuals
      are at very high risk of bone marrow failure, cancer, and pulmonary fibrosis. A
      mutation in one of six different telomere biology genes can be identified in 50
      60% of these individuals. DKC1, TERC, TERT, NOP10, and NHP2 encode components of
      telomerase or a telomerase-associated factor and TINF2, a telomeric protein.
      Progressively shorter telomeres are inherited from generation to generation in
      autosomal dominant dyskeratosis congenita, resulting in disease anticipation. Up
      to 10% of individuals with apparently acquired aplastic anemia or idiopathic
      pulmonary fibrosis also have short telomeres and mutations in TERC or TERT.
      Similar findings have been seen in individuals with liver fibrosis or acute
      myelogenous leukemia. This report reviews basic aspects of telomere biology and
      telomere length measurement, and the clinical and genetic features of those
      disorders that constitute our current understanding of the spectrum of illness
      caused by defects in telomere biology. We also suggest a grouping schema for the
      telomere disorders.

PMID- 21189496
TI  - Outsourcing. Let them take the strain.

PMID- 21189497
TI  - Sustainability. Carbon chameleons.

PMID- 21189498
TI  - Rationalising estates. Changing rooms.

PMID- 21189499
TI  - Risk management. Take the drama out of a crisis.

PMID- 21189500
TI  - Hospital failures. Something's got to give--the system has too many hospitals.

PMID- 21189501
TI  - White paper. Lansley seeks to reassure GPs on commissioning.

PMID- 21189502
TI  - Accountability. Trusts to be tested on dementia.

PMID- 21189503
TI  - Patient safety. NHS London revisits closure plans.

PMID- 21189504
TI  - Quality, innovation, productivity and prevention. 'Shared decisions' mean fewer
      operations.

PMID- 21189505
TI  - Dickon Weir-Hughes on being good enough.

PMID- 21189506
TI  - On cancer detection. Early diagnosis could save lives.

PMID- 21189507
TI  - Integrated health. Breaking through savings barriers.

PMID- 21189508
TI  - Commissioning. GPs must cross the skills gap.

PMID- 21189509
TI  - Human resources. Talking about a revolution.

PMID- 21189510
TI  - First aid training for students.

PMID- 21189512
TI  - Better outcomes await if you respond wisely to heart attack symptoms.  Research
      shows that too many heart patients fail to make smart, fast decisions at the
      onset of heart attack symptoms, even if they've been instructed on how to react.

PMID- 21189511
TI  - Data sharing.

PMID- 21189513
TI  - Make heart-healthy choices this holiday season. Recent research shows that weight
      control may also preserve kidney function, a vital component of cardiovascular
      health.

PMID- 21189514
TI  - Understand the risks of anxiety in patients with ICDs.  Type-D patients who have
      ICDs and experience anxiety have a higher risk of arrhythmias, according to a
      recent study.

PMID- 21189515
TI  - It takes more than statins to keep cholesterol under control. Research shows that
      many patients on statin therapy still aren't reaching their LDL cholesterol
      targets.

PMID- 21189516
TI  - Heart failure drugs underprescribed.  Aldosterone antagonists are typically used
      in conjunction with other medications.

PMID- 21189517
TI  - My doctor says I have a calcium build-up in my aortic valve and that the only
      solution is surgery to replace it.  How serious is calcium in the valve, and are
      there any alternatives to valve replacement?  Also, what should I expect after
      the surgery (my doctor has said the replacement would be a pig valve)?

PMID- 21189518
TI  - Vitamin D may play a major role in heart health.  Protect yourself by making sure
      you get enough of this critical vitamin.

PMID- 21189519
TI  - [Reference pricing system for triptans: Chaos in the pharmac].

PMID- 21189520
TI  - [Tapentadol. Opioid analgesic and norepinephrine reuptake inhibitors].

PMID- 21189521
TI  - [Present-day treatment of arterial hypertension].
AB  - The treatment goal of patients with arterial hypertension is to reduce the blood
      pressure below 140/90 mmHg with the aim to lower the risk of subsequent
      cardiovascular diseases and to prolong patient's longevity. There are five main
      classes for blood pressure treatment: ACE-inhibitors, angiotensin II receptor
      blockers, beta-receptor blockers, calcium channel blockers, and thiazide
      diuretics. All these antihypertensive drugs have in common that they are able to
      lower the arterial blood pressure in a similar range. If drugs have similar
      effects, those with additional beneficial effects on patient's comorbidity should
      be preferred. Some antihypertensive drugs such as inhibitors of the renin
      angiotensin-aldosteron system (RAAS) additionally have organ protective
      properties. ACE-inhibitors and angiotensin receptor blockers should be preferred
      in patients with a high cardiovascular risk such as coronary heart disease, heart
      failure, diabetes, and chronic kidney disease. A preferred approach is the
      initial prescription of a low dose combination to bring more hypertensive
      patients to their target blood pressure. Most combination drugs contain a
      thiazide diuretic. A better combination especially for diabetics seems to be a
      calcium channel blocker together with a RAAS inhibitor. A possible combination
      for patients with coronary heart disease or heart failure is a RAAS inhibitor
      combined with a beta-receptor blocker.

PMID- 21189522
TI  - [New guideline for cardiopulmonary resuscitation. The most important measure is
      the heart massage].

PMID- 21189523
TI  - [Image of the month. Discovery of a post-traumatic aortic isthmus pseudoaneurysm
      15 years after a traffic accident].

PMID- 21189524
TI  - [How I treat ... some skin conditions by cooling].
AB  - Cold application to the skin is commonly used in dermatology. The modalities of
      application are diversified and condition the temperature reached in the skin and
      the therapeutic result. Hense, the term cryotherapy without further precision
      remains little informative. The sensibility to cold of the diverse types of
      cutaneous cells is heterogeneous, as well as that of healthy and neoplastic
      tissues.

PMID- 21189525
TI  - [Clinical case of the month. The "classic" triad presentation of mucinous
      bronchiolo-alveolar carcinoma].
AB  - The case of a 59-year-old female complaining of cough of recent onset, abundant
      salty expectoration and lung condensation is presented. This "triad" constitutes
      a rare but nearly pathognomonic presentation of mucinous bronchioloalveolar
      carcinoma (BAC) of the lung.

PMID- 21189526
TI  - [Clinical case of the month. Cystic lymphangioma of the mesentery].
AB  - Cystic lymphangioma of the mesentery is a benign condition, probably of
      malformative origin, and frequently appearing in infancy. Its symptomatology can
      be very polymorphic. Its diagnosis is suspected by ultrasonography and computed
      tomography, and definitely confirmed by pathology. About a recent case of cystic
      lymphangioma of the mesentery diagnosed and operated on at the university
      hospital of Liege in an adult patient, the authors review its classification and
      its therapeutic strategy. Surgical resection is indicated in symptomatic cystic
      lymphangioma.

PMID- 21189527
TI  - [Actinic keratosis in tune with field photocarcinogenesis. A revisited concept].
AB  - Actinic keratosis should no more be considered as a single neoplasm calling for
      an individual treatment. The concept of actinic photocarcinogenesis presently
      turns upside down the perception of skin cancers induced by nonionizing
      electromagnetic radiations. Currently, the clinician should cope with the whole
      skin area that has been damaged by chronic exposures to the visible and the
      invisible spectrum of the light. The therapeutic archetypes are 5-fluorouracile
      5% and imiquimod 5% carefully applied to the skin area.

PMID- 21189528
TI  - [Cocaine induced psychotic disorders: a review].
AB  - Cocaine remains the second most used illicit drug in Europe, after cannabis,
      though levels of use vary between countries. This psychostimulant has become a
      noticeable part of the European drug scene. Cocaine dependence, a chronic,
      relapsing and multifactorial disorder, is a significant worldwide public health
      problem with somatic, legal, social, cognitive and psychological complications.
      The relationship between clinical psychotic symptoms and use of specific
      substances other than cannabis has received minimal attention in the literature.
      Psychotic symptoms and experience of paranoia and suspiciousness are reported
      during the use and the withdrawal of cocaine. Furthermore, although psychotic
      symptoms were found to be common among substance users, the risk for development
      of chronic psychotic disorder was found. In the light of recent epidemiological
      data stating that there is an increased cocaine use, that there is an increased
      number of patients entering drug treatment for primary cocaine use in Europe for
      several years and that cocaine users are an heterogeneous group, we made a review
      on the specific topic of cocaine-induced psychotic disorders. This review is
      based on Medline, EMBASE, PsycINFO and Google Scholar searches of English and
      French-language articles published between 1969 and February, 2010.

PMID- 21189529
TI  - [The long QT syndrome].
AB  - The congenital long QT syndrome (LQTS) is a hereditary cardiac disease
      characterized by a prolongation of the QT interval > 440 ms at rest ECG
      associated with a high risk of ventricular arrhythmias (torsade de pointe).
      Clinical manifestations are syncope and sudden cardiac death. The implicated
      genes encode cardiac ion channel subunits or proteins involved in modulating
      ionic currents. The diagnosis of LQTS can be complex in borderline cases.
      Etiology, pathogenesis, diagnosis and treatment are discussed.

PMID- 21189530
TI  - [How to explore ... congenital isolated hypogonadotrophic hypogonadism].
AB  - Congenital Isolated hypogonadotropic hypogonadism (CIHH) is caused by an
      inherited mechanism of impairment of the pituitary-gonadal axis, interfering with
      gonads' control. Currently, different forms of HHCI with (Kallmann syndrome or
      KS) or without anosmia-hyposmia are known. There are six forms of KS already
      described but in several cases no genetic mutation is found. The genetic
      anomalies already described are: KAL1 (locus Xp23) coding for anosmine-1, KAL-2
      or FGFRI (8p11. locus 2 - p11.1) coding for Fibroblast Growth Factor Receptor 1
      (FGFR1), KAL4 or PROk2 (locus 3p21.1) and KAL3 or ProKR2 (locus 20p13) coding
      respectively for the Prokinecitin-2 and its receptor, KAL5 or CHD7 (locus_8q12.1)
      coding for a chromodomain helicase DNA-binding protein-7 gene (CHD7) and lastly
      KAL6 or FGF8 (10Q 24 loci) coding for Fibroblast Growth Factor 8. The other
      genetic anomalies without anosmia are less frequent. These are associated either
      with Gnrhl gene (8p2-11. 2), GnRHR (4q21.2), GPR54 (19p13),TAC3R or neurokinine
      receptor 3 (4 q 25), LH (19q13.32) or FSH (11p13). The isolated congenital
      hypogonadotrophic hypogonadism phenotype is variable depending on gender, the
      importance of the deficit, and ultimately, according to a specific regulatory
      mechanism of the axis, affected by an inherited genetic anomaly. In this review,
      we describe the essential aspects of the different phenotypes and genotypes of
      HHCI, in order to assess clinicians an early disease's diagnosis and management.

PMID- 21189531
TI  - [Medication of the month. Prasugrel (Efient): potent thienopyridine antiplatelet
      agent].
AB  - Prasugrel (Efient), a thienopyridine of third generation, is a prodrug that, like
      clopidogrel, requires conversion to an active metabolite before binding to the
      platelet P2Y12 receptor to confer antiplatelet activity. At the currently studied
      doses, prasugrel inhibits adenosine diphosphate-induced platelet aggregation more
      rapidly, more consistently, and to a greater extent than do standard and higher
      doses of clopidogrel. The risk of myocardial ischemic events in patients with
      acute coronary syndromes has been shown to be reduced by means of platelet
      inhibition. Dual-antiplatelet therapy with aspirin and clopidogrel has become the
      cornerstone of treatment to prevent thrombotic complications of acute coronary
      syndromes and percutaneous coronary intervention. In patients with acute coronary
      syndromes (TRITON-TIMI 38 trial), prasugrel therapy was associated with
      significantly reduced rates of ischemic events, including stent thrombosis, but
      with an increased risk of major bleeding. Subjects with diabetes mellitus tended
      to even have a greater reduction in ischemic events with prasugrel. In Belgium,
      Efient is currently reimbursed for 1 year in patients with an acute coronary
      syndrome and scheduled for a percutaneous coronary intervention (PCI) who present
      at least one of the following criteria: primary PCI for ST-elevation myocardial
      infarction, stent thrombosis despite treatment with clopidogrel, or diabetes
      mellitus.

PMID- 21189532
TI  - [Medication of the month. Sitagliptin-metformin fixed combination (Janumet)].
AB  - Type 2 diabetes is a complex disease with the coexistence of several
      pathophysiological abnormalities such as a defect of insulin secretion, a
      relative hyperglucagonaemia, an increased hepatic glucose production and a
      muscular insulin resistance. In order to tackle all these abnormalities, the
      coadministration of several drugs with complementary actions is frequently
      required. Janumet is a fixed-dose combination of sitagliptin, a specific
      inhibitor of dipeptidylpeptidase-4 that blocks the rapid degradation of so-called
      incretin hormones (resulting in a potentiation of insulin secretion and reduction
      of glucagon secretion in a glucose-dependent manner), and of metformin, a
      biguanide compound that reduces glucose hepatic production and slightly improves
      insulin sensitivity. This pharmacological combination improves glucose control
      without inducing hypoglycaemia or weight gain. The tolerance profile is rather
      good, with (digestive) side effects and contraindications (risk of lactic
      acidosis in case of renal insufficiency) attributable to metformin. Janumet
      (50/850 mg or 50/1.000 mg), twice daily, is indicated in the treatment of type 2
      diabetes and is currently reimbursed in Belgium after failure of metformin
      monotherapy or the prior demonstration of the efficacy of adding sitaglitptin
      (Januvia) to metformin.

PMID- 21189533
TI  - [Clinical vignettes. How to diagnose the cause of edema, a clinical approach].
AB  - Oedema is a frequent disorder and the easily detectable consequence of an
      increase of fluid located in the interstitial tissue. It could be localized or
      generalized and related either to a primary disturbance of hemodynamics at the
      capillary level, due to a modification of the Starling's law components with
      secondary water and saline retention, or to a primary retention of salt and water
      linked to a kidney abnormality. Generalized forms are pitting oedema, most often
      painless, white, bilateral and symmetric, distributed at the lower part of the
      body (localisation according to the gravitation law). They are different in their
      characteristics from localized oedema or lymphoedema which are tough. We propose
      a diagnostic approach based on medical history, clinical examination which allows
      a confident medical diagnosis and so an adapted therapy.

PMID- 21189534
TI  - [The effect of baicalein on bleomycin-induced fibrosis in lungs of rats].
AB  - AIM: To explore the effect of baicalein (Bai-Chinese Traditional Medicine) on
      bleomycin (BLM)-induced fibrosis in lungs of rats and its possible mechanism.
      METHODS: Sixty-eight male Sprague-Dawley rats were randomly divided into 4
      groups: BLM plus Bai group, BLM plus normal saline (NS) group, NS plus Bai group,
      and NS plus NS group. The rats were received single intratracheal instillation of
      BLM (5 mg kg(-1) bw) or equal volume of NS as control, and received
      intraperitoneal injection o f Bai (12.5 mg x kg(-1) bw) or the same volume of NS
      asvehicle for 28 d. The hydroxyproline content, the collagen area, the mRNA
      expression of Col I (alpha), and the myofibroblasts in lung were examined.
      RESULTS: The content of hydroxyproline, the percentage of collagen area, the mRNA
      expression of Col I (alpha), and the amount of myofibroblast were increased in
      lungs of rats on day 28 after intratracheal instillation of BLM, compared with
      that in lungs of the control rats, respectively( All P < 0.01). The above
      abnormal changes were ameliorated by Bai (12.5 mg x kg(-1) x d(-1) ip, x 28 d
      (All P < 0.05). CONCLUSION: Bai has anti-action on BLM-induced fibrosis in lung,
      and that the above action of Bai is related to the blockage of synthesis of type
      I collagen and the decrease of myofibroblast in lung.

PMID- 21189535
TI  - [Effects of different gender and long-term exercise on hydroxyl radical
      metabolism and lipid peroxidation in the liver of rats].

PMID- 21189536
TI  - [The preventative effects of protein tyrosine kinase on the inflammation and
      airway remondeling in lung of guinea pigs with bronchial asthma].
AB  - AIM: To investigate the effects of protein tyrosine kinase on the inflammation
      and airway remodeling in lung of guinea pigs with bronchial asthma. METHODS: 30
      adult male guinea pigs were randomly divided into 3 groups (n=3): control group
      (C group), asthmatic group(A group)and genistein group (B group). Asthmatic model
      was established by ovalbumin intraperitoneal injection and ovalbumin inhalation.
      The total cell and the proportion of inflammatory cell in bronchial alveolar
      lavage fluid(BALF), inflammatory cell infiltration and index of remodeling of
      bronchiole were measured, respectively. The expression of p-tyrosine in lung
      tissue was examined by immunohistochemistry. RESULTS: The total cell and
      proportion of eosinophil in BALF of A group were significantly higher than that
      of C group (P < 0.01), but compared with A group, the total cell and proportion
      of eosinophil in BALF of B group were much lower (P < 0.01). The number of
      eosinophile and lymphocyte of bronchiole in A group were significantly higher
      than that of C group (P < 0.01), but compared with A group, the number of
      eosinophile and lymphocyte in bronchiole of B group were much lower (P < 0.01).
      Compared with A group, the remodeling of bronchiole of B group was significantly
      relieved (P <0.01), there was no difference between B and C group (P > 0.05).
      Immunohistochemistry indicated that in A group the p-tyrosine was more positively
      expressed at the bronchial smooth muscle, bronchial epithelium, smooth muscle of
      vessel and inflammatory cell, especially at smooth muscle of bronchi and vessel
      and inflammatory cell than that of C group (P <0.01), there was no difference
      between B group and C group (P > 0.05). CONCLUSION: PTK played a key role in
      inflammation and bronchial remodeling in lung of guinea pigs with bronchial
      asthma. The Protein tyrosine kinase inhibitor genistein could prevent and inhibit
      the inflammation and bronchial remodeling in lung of guinea pigs with bronchial
      asthma.

PMID- 21189537
TI  - [Effects of sinomenine on the cultured smooth muscle cell MAPK PKC activities and
      intracellular free Ca2+].

PMID- 21189538
TI  - [Effects of cold stress on blood cell parameters of partial sleep deprivation
      mice].
AB  - AIM: To investigate the effect of cold, partial sleep deprivation, partial sleep
      deprivation plus cold on blood routine parameters and erythrocyte sedimentation
      rate of mice. METHODS: Twenty-four Mus musculus mice were divided into four
      groups (n=6) randomly: (1) control, (2) cold group: mice were treated with (10 +/
      2) degrees C cold stimulation for four hours per day, (3) partial sleep
      deprivation group: mice were deprived sleep from 18:00 to 9:00 next day, (4)
      partial sleep deprivation plus cold group: mice were treated with cold
      stimulation based on partial sleep deprivation. After four days treatment, the
      mice were sacrificed and the blood was collected to detect the blood routine
      parameters and erythrocyte sedimentation rate. RESULTS: Compared with the
      control, cold stimulation would increase the contents and proportion of
      lymphocyte significantly. Partial sleep deprivation would decrease the white
      blood cell contents, lymphocyte contents and lymphocyte proportion significantly.
      After treated with cold stimulation plus partial sleep deprivation, the white
      blood cell and lymphocyte contents decreased and the erythrocyte sedimentation
      rate increased evidently compared with other three groups. CONCLUSION: Partial
      sleep deprivation could inhibit immune function of the mice. When the mice were
      treated with cold stimulation plus partial sleep deprivation, the immune function
      of the mice would be inhibited further more and at the same time the erythrocyte
      sedimentation rate increased significantly.

PMID- 21189539
TI  - [Effect of Ophiopogon japonicus polysaccharide MDG-1 on the expression of leptin
      in endothelial cells].

PMID- 21189540
TI  - [Effects of cold-stress stimulation on filial growth and development of pregnant
      mice].
AB  - AIM: To inspect the effects of cold-stress on filial growth and development of
      pregnant mice. METHODS: Pregnant mice were divided into pregnant control
      group(PN) and pregnant cold-stress group (PC). The PC were kept in (4 +/- 2) C
      from 8:00 to 12:00 every day and the PN were kept in 25 degrees C. After 18 days,
      the blood pressure of pregnant mice were measured, and the weight of fetus,
      placenta and amniotic fluid were recorded. The natal mice visceral organs weight,
      visceral organs weight and body weight ratio were also measured. Growth curve and
      increment ratio curve of body weight were protracted every day from 1 st day to
      44th day. Blood pressure of all filiality were measured in 8 weeks after they
      were born. RESULTS: The blood pressure in PC was increased than that in PN (P <
      0.05), the weight of fetus, placenta and amniotic fluid of PC decreased
      significantly compared with PN (P < 0.01). The filial visceral organ weight of PC
      reduced obviously compared with PN (P < 0.05), while the visceral organs weight
      and body weight ratio had no statistical meanings between the offspring of PC and
      PN (P > 0.05). Obvious difference of growth curve of the two filial groups was
      also existed until sexual maturity, but increment ratio curve of body weight of
      the two filial groups was basically fitted close. Filial blood pressure of PC was
      evidently higher than that in PN. CONCLUSION: Cold-stress stimulations seriously
      affect filial growth and development of pregnant mice.

PMID- 21189541
TI  - [Effects of stress on the cognitive function and physical fitness and its
      biological mechanisms].
AB  - AIM: To study the effects of stress on the cognitive function and physical
      fitness and its biological mechanisms, provide scientific basis for seeking
      protective measures to reduce stress-induced damage. METHODS: The model of
      restraint stress was adopted in our experiment. Step-down test and exhaustive
      swimming test were used to measure the learning and memory function and physical
      fitness in mice, respectively. The contents of GC in plasma, hippocampus LTP,
      ECG, myocardial ultra-structure, cell apoptosis rate and the level of Hsp70
      expression of myocardium in rats were detected. RESULTS: Compared with control
      group, the impairment of learning and memory function and decline of exercise
      tolerance were observed in restraint stress group. The elevation in plasma GC
      levels, ECG abnonrmality, and cell apoptosis rate were also observed under
      restraint stress. Furthermore, myocardial structure was damaged, and myocardial
      Hsp70 expression and hippocampus LTP were suppressed in restraint stress group
      than those in the control. CONCLUSION: Stress may cause the neuro-endocrine
      dysfunction and homeostasis disorder, and then, lead to the cognitive function
      and physical fitness damage consequently.

PMID- 21189542
TI  - [Effect of ipriflavone on growth and blood testosterone level in male rats].

PMID- 21189543
TI  - [Effects of cold stress on energy metabolism in the chicken].
AB  - AIM: To investigate the effect of cold stress on the energy metabolism in Yisha
      chickens. METHODS: Male Yisha chickens were subjected to acute (0.25, 1, 3, 6, 12
      and 24 h) and chronic (5, 10 and 20 d) cold stress (12 +/- 1 degrees C). This
      study detected uncoupling protein (UCP) mRNA levels in gastrocnemius, glucagons
      (GLU) content in blood plasma and insulin (INS), blood glucose (BG) and free
      fatty acid (FFA) content in serum in the chicken. RESULTS: The results were as
      follow: with the time lapsing during acute cold stress, UCP mRNA levels gradually
      increased, the content of INS and FFA showed fluctuant change, GLU content
      gradually increased, and BG content first increased and then decreased. During
      chronic cold stress, UCP mRNA levels significantly increased compared with their
      control group at every stress time point, and the content of INS, GLU, BG and FFA
      were all gradually increased with the time lapsing. CONCLUSION: Cold stress could
      change the energy metabolism in chickens. And the different extent cold stress
      would produce different effects on the energy metabolism.

PMID- 21189544
TI  - [Effects of acute hypoxia on plasma metabolome in mice].
AB  - AIM: To explore the metabolic effects of acute hypoxia on mice plasma. METHODS:
      Fourteen mice were randomly divided into two groups: control and hypoxia group.
      The mice of hypoxia group were exposed to a simulated altitude of 6000 meters for
      8 hours. Nuclear magnetic resonance spectrometer was used to identify the
      metabolic changes after acute hypoxia. RESULTS: Compared with control, the most
      notable significantly after acute hypoxia exposure. remarkably and lactate
      increased metabolic changes in plasma were as follows: camrnitine decreased
      levels of lipids and pyruvate, alanine, taurine, Decreases in levels of beta-HB,
      ethanol glycerol, glutamate, glycine and serine, and increased choline, glucose,
      and glutamine were also observed in hypoxia group. CONCLUSION: Significant
      changes in the plasma carbohydrate, lipid and amino acid profiles were observed
      following acute hypoxia, suggesting a hypoxia-induced alteration in energy and
      related substances metabolism.

PMID- 21189545
TI  - [Influence of aniracetam on the learning ability, memory ability and the
      expression of BCL-2 of hippocampal in vascular dementia model rats].

PMID- 21189546
TI  - [The role of NO resulted from neuronal nitric oxide synthase in the metabotropic
      glutamate receptor2/3 mediated-brain ischemic tolerance].
AB  - AIM: To explore the role of nitric oxide (NO) resulted from nNOS in the mGluR2/3
      mediated-brain ischemic tolerance induced by cerebral ischemic preconditioning
      (CIP), the present study is undertaken to observe the influences of alpha-methyl
      (4-tetrazolyl-phenyl) glycine (MTPG), an antagonist of mGluR2/3, on the
      expression of nNOS during the induction of the brain ischemic tolerance based on
      confirming the blocking effect of MTPG on the induction of the tolerance.
      METHODS: Thirty-six Sprague-Dawley rats, whose vertebral arteries were
      permanently occluded, were randomly divided into sham, CIP, ischemic insult, CIP+
      ischemic insult, MTPG+ CIP and MTPG+ CIP+ ischemic insult groups. Thionin
      staining and immunohistochemistry were used for neuropathological evaluation and
      assay of nNOS expression in the hippocampal CA1 subregion of the rats. RESULTS:
      The expression of nNOS showed moderate and extreme up-regulation in the CIP and
      ischemia groups, respectively, compared to the sham group. The preceded CIP
      blocked in certain extent the extreme up-regulation of nNOS induced by brain
      ischemia in CIP + ischemia group. Administration of MTPG via lateral cerebral
      ventricle 20 min before CIP blocked the up-regulation of nNOS induced by CIP, but
      had no influence on the pyramidal neuronal survival. While in the MTPG+ CIP+
      ischemic insult group, the expression of nNOS was stronger than that in the MTPG
      + CIP group, and the up-regulation was accompanied with obvious delayed neuronal
      death. Discussion concerned illustrated that the relative intensive up-regulation
      of nNOS in this group might be attributed to brain ischemia other than MTPG.
      CONCLUSION: NO resulted from nNOS participated the induction of mGluR2/3 mediated
      brain ischemic tolerance as a downstream molecule of activation of mGluR2/3
      during CIP.

PMID- 21189547
TI  - [Effects of electromagnetic radiation on RAF/MEK/ERK signaling pathway in rats
      hippocampus].
AB  - AIM: To study the development of changes for signaling molecules related to
      Raf/MEK/ERK pathway in hippocampus of rats after electromagnetic radiation, and
      investigate the mechanisms of radiation injury. METHODS: Rats were exposed to X
      HPM, S-HPM and EMP radiation source respectively, and animal model of
      electromagnetic radiation was established. Western blot was used to detect the
      expression of Raf-1, phosphorylated Raf-1 and phospholylated ERK. RESULTS: The
      expression of Raf-1 down-regulated during 6 h-14 d after radiation, most
      significantly at 7 d, and recovered at 28 d. There was no significant difference
      between the radiation groups. The expression of phosphorylated Raf-1 and
      phosphorylated ERK both up-regulated at 6 h and 7 d after radiation, more
      significantly at 6 h, and the two microwave groups were more serious for
      phosphorylated ERK. During 6 h-14 d after S-HPM radiation, the expression of
      phosphorylated Raf-1 increased continuously, but phosphorylated ERK changed
      wavily, 6 h and 7 d were expression peak. CONCLUSION: Raf/MEK/ERK signaling
      pathway participates in the hippocampus injury induced by electromagnetic
      radiation. The excessive activation of ERK pathway may result in the apoptosis
      and death of neurons, which is the important mechanism of recognition disfunction
      caused by electromagnetic radiation.

PMID- 21189548
TI  - [Formalin inflammatory pain induced hippocampal neuronal apoptosis of rats].
AB  - AIM: To investigate whether formalin inflammatory pain can induce hippocampal
      neuronal apoptosis of rats or not. METHODS: Rats were subcutaneously injected
      with 0.2 ml 0.5% formalin into the ventral surface of right hind paw to induce
      periphery inflammatory pain. The flinches of rats were counted to observe their
      painful reaction. Flow cytometry was used to assay the ratio of apoptosis of
      hippocampal neurons. The immunohistochemistry was used to observe the expression
      of p53 protein in hippocampal subregions. RESULTS: Compared with control group,
      the apoptotic ratio of hippocampal neurons was significantly increased in rats
      with inflammatory pain, and formalin inflammatory pain induced upregulation of
      p53 protein expression in all hippocampal subregions. Both the apoptotic ratio
      and the p53 protein expression peaked on the third day after the formalin
      injection. The twice injection of formalin into the hind paws of rats resulted in
      an enhancement of painful reaction and increase in apoptotic ratio of hippocampal
      neurons compared with the rats of injection formalin once group. CONCLUSION:
      Formalin inflammatory pain can induce the hippocampal neuronal apoptosis in rats
      with a certain time course. Neuronal apoptosis is relevant to the intensity of
      pain. The up-regulation of p53 protein expression may implicate in the induction
      of hippocampal neuronal apoptosis in rats with inflammatory pain.

PMID- 21189549
TI  - [The relationship between the plasma concentration of urotension II (U II) and
      NO, NOS in spontaneous hypertensive rats and influence of candesartan].

PMID- 21189550
TI  - [The association of hippocampal glutamate with depression and the effects on
      gastric mobility].
AB  - AIM: To explore the relationship between the pathology of depression and
      glutamate (Glu) in hippocampus, and the effect on gastric mobility. METHODS:
      Depression model was established by using the chronic unpredicted mild stress
      (CUMS). And stereotaxic and intra-hippocampal microinjection were also used in
      this experiment. Rat emotion and behaviors were observed by the change in body
      weight, sucrose preference-test, open field-test and forced swimming-test.
      Intragastric pressure and mobility were recorded with the instrument of
      Powerlab/8sp. RESULTS: Compared with the control, 21-day CUMS significantly
      reduced the increase in body weight, rat sucrose preference, locomotor activity
      and rearing in open field test, while it significantly increased duration of
      immobility time in forced swimming test. Meanwhile, magnitudes of intragastric
      pressure and mobility were significantly declined after 21 days CUMS.
      Microinjection of Glu into hippocampus mimics the behaviors which were produced
      in CUMS. The down-rang of gastric mobility in the group of Glu injection was
      smaller than CUMS, but was much larger than the control. Intrahippocampal
      microinjection of MK-801 attenuated depression-like behaviors induced by stress,
      weakened stress-induced inhibition of intragastric pressure, and augmented the
      magnitudes of gastric contraction. CONCLUSION: Glu and NMDA receptor in
      hippocampus are to do much with the etiology of stress- induced depression. They
      are not only concerned with behavioral changes induced by stress, but also with
      the variation of gastric activities, nevertheless, differences exist between the
      effects of behaviors and gastric activities.

PMID- 21189551
TI  - [Effects of different temperature diets on glucose and lipid metabolism, sexual
      hormone and blood rheology in female rats].

PMID- 21189552
TI  - [Activation of periphery group III metabotropic glutamate receptors inhibits
      formalin-induced activation of spinal p38-MAPK in rats].
AB  - AIM: To explore the effects of periphery injection of L-SOP on the activation of
      p38MAPK in spinal cord in formalin pain model in rats. METHODS: Fourty-eight male
      Wistar rats were divided randomly into four groups (n=12): NS group and three
      different dose of L-SOP groups. For each group, 6 rats used to observe flinching
      and licking time every as nociception behavior 3 minutes in 1 hour after formalin
      injected and the other 6 rats used to observe the activation of p38(P-p38) by
      Western blotting. RESULTS: All the three different groups of L-SOP could inhibit
      nociception behavior in the tonic phase,and 250 nmoVl/L and 500 nmol/L groups
      could suppress not only in the tonic phase but also in the acute phase. 250
      nmol/L and 500 nmol/L groups could reduce activated or phosphorylated p38MAPK in
      spinal cord. CONCLUSION: Periphery injection of L-SOP can reduce nociceptive
      behavior and phosphorylated p38MAPK in the spinal cord in formalin-induced
      hyperalgia, it is suggested that there is functional expression of mGluRs III in
      the periphery and is involved in the processing of peripheral noxious
      informations.

PMID- 21189553
TI  - [The inhibition of tamoxifen on sodium channel in SHG-44 glioma cell-line].
AB  - AIM: To explore the effect of tamoxifen on voltage-dependent sodium channels in
      SHG-44 glioma cell line. METHODS: Whole-cell patch clamp technique was used to
      record the Na currents in SHG-44 cell line and to investigate the effect of
      tamoxifen of different concentration on this channel currents. RESULTS: This
      channel activated and inactivated quickly. Tamoxifen could significantly decrease
      the amplitude of Na currents of SHG-44 cell line. This block effect was dose
      dependent and voltage dependent. When the holding potential was 0 mV, 8
      micromol/L tamoxifen could block this currents 69%. The half inhibition
      concentration (IC50) was 5.54 micromol/L. CONCLUSION: Tamoxifen could
      significantly block the voltage dependent sodium channel in malignant glioma cell
      line SHG-44. It might be one of the mechanisms that tamoxifen inhibit glioma
      proliferation. clamp technique was used to record the Na currents in SHG-44 cell
      line and to investigate the effect of tamoxifen of different concentration on
      this channel currents. RESULTS: This channel activated and inactivated quickly.
      Tamoxifen could significantly decrease the amplitude of Na currents of SHG-44
      cell line. This block effect was dose dependent and voltage dependent. When the
      holding potential was 0 mV, 8 micromol/L tamoxifen could block this currents 69%.
      The half inhibition concentration (IC50) was 5.54 micromol/L. CONCLUSION:
      Tamoxifen could signifi-cantly block the voltage dependent sodium channel in
      malignant glioma cell line SHG-44. It might be one of the mechanisms that
      tamoxifen inhibit glioma proliferation.

PMID- 21189554
TI  - [The protective effect of pharmacological postconditioning of cariporide and GSH
      on ischemia/reperfusion injury].

PMID- 21189555
TI  - [Effects of unilateral lesion of the nigrostriatal pathway by 6-OHDA on the
      neuronal activities of the pedunculopontine nucleus and the ventrolateral
      thalamic nucleus].
AB  - AIM: To investigate the changes in neuronal activities of the pedunculopontine
      nucleus (PPN) and the ventrolateral thalamic nucleus (VL) after unilateral 6
      hydroxydopamin (6-OHDA) lesioning of the striatum in rats. METHODS: Extracellular
      single-unit recordings were perin normal rats and 6-OHDA lesioned rats to observe
      the firing rate and firing pattern occurring in PPN and VL neurons. RESULTS: The
      firing rate of PPN neurones significantly increased from (8.31 +/- 0.62) Hz in
      normal rats to (10.70 +/- 0.85) Hz in 6-OHDA lesioned rats. The firing pattern
      changed towards more irregular and bursty when compared with the normal rats,
      with the firing rate increasing in regular pattern. The firing rate of VL
      neurones in normal rats and 6-OHDA lesioned rats were (6.25 +/- 0.54) Hz and
      (5.67 +/- 0.46)Hz respectively, whereas to normal animals. Surthere were no
      significant differences in these two groups. In addition, the firing pattern did
      not change in VL compared prisingly, the firing rate in burst pattern decreased
      significantly. CONCLUSION: These findings demonstrate that PPN neurons are
      overactive in 6-OHDAlesioned rats, indicating the participation of this nucleus
      in the pathophysiology of parkinsonism and the activities of VL neurons might be
      regulated by projection from PPN to VL.

PMID- 21189556
TI  - [The effect of formalin-induced pain on CCK in rat spinal cord neurons].
AB  - AIM: CCK is one of the strongest endogenous anti-opioid substances and suppresses
      morphine tolerance which results from long term use of morphine. This study
      explores the modulatory effect of CCK on pain formalin-induced. METHODS: The
      effect of formalin-induced pain on CCK immunoreactivity in rat sensory neurons
      was observed through immunohistochemistry technique. RESULTS: After 1 h of
      subcutaneous injection of formalin in one paw of rats, the number of positive
      neurons of CCK immunoreactivity in spinal cord neurons was obviously increased
      and greater than that of non-injection side (P <0.01). The semi-quantitative
      optical density average values of CCK immunoreactivity neurons were 0.397 +/-
      0.014 and 0.295 +/- 0.007 in injection side and non-injection side respectively,
      the difference was obvious (P < 0.01). After 3 h of subcutaneous injection of
      formalin in one paw of rats, the semi-quantitative optical density average values
      of CCK immunoreactivity neurons were 0.366 +/- 0.009 and 0.303 +/- 0.005 in
      injection side and noninjection side respectively, the difference was significant
      (P < 0.01). CONCLUSION: Formalin-induced pain can significantly change semi
      quantitative optical density average value of CCK immunoractivity in spinal cord
      neurons, this indicates CCK participates in modulation of pain.

PMID- 21189557
TI  - [Changes of leptin levels in serum and myocardium after myocardial
      ischemia/reperfusion injury].
AB  - AIM: To explore the effect of rat myocardial ischemia/reperfusion injury on
      leptin levels in serum and myocardium, and discuss the role of leptin in
      myocardial ischemia/reperfusion injury. METHODS: A myocardial
      ischemia/reperfusion injury model of rats was established, serum lactate
      dehydrogenase (LDH) and leptin levels were detected, and histopathological
      changes and leptin expressions in myocardium were investigated by hematoxylin
      eosin staining and immunohistochemistry, respectively. RESULTS: Serum LDH of
      ischemia and reperfusion groups increased significantly (P < 0.05), suggesting
      the model was successfully established and a certain degree of local myocardial
      injury was induced. Serum leptin of ischemia group (6.34 +/- 2.49) ng/ml was
      significantly lower than control group (7.50 +/- 2.93 ng/ml, P <0.05). Leptin
      levels recovered gradually after reperfusion, reached (8.32 +/- 1.74)ng/ml at 2 h
      after reperfusion, which recovered to the level before injury (8.38 +/- 2.56)
      ng/ml, and showed a trend to increase as reperfusion time was elongated.
      Immunohistochemistry results showed that as compared with sham-operation group,
      myocardial leptin protein expressions of the other four groups were all
      significantly lower (P < 0.01), and decreased in order by 45 min ischemia/1 h
      reperfusion, 45 min ischemia/3 h reperfusion, 45 min ischemia and 45 min
      ischemia/2 h reperfusion. CONCLUSION: Leptin level in the blood decreases
      significantly at the early 45 min after myocardial ischemia/reperfusion injury,
      and its expression in myocardium also decreases significantly. There may be a
      certain relationship between the pathological injury of myocardium and the
      changes of leptin.

PMID- 21189558
TI  - [The effects of urea on ECG and the sodium currents of ventricular myocyte in
      mice].
AB  - AIM: To observe the effects of urea on ECG and sodium currents of ventricular
      myocyte in mice. METHODS: ECG and patch clamp techniques were used in the
      experiments, to record ECG of mice and sodium currents of ventricular myocyte in
      mice. RESULTS: Urea could lead mice heart rate evidently slow down (P < 0.01)
      with concentration dependent. The heart rate were (556 +/- 29, 469 +/- 37, 378 +/
      48) b minT in low, middle, high groups respectively before using urea and (612
      +/- 27, 615 +/- 23, 619 +/- 26) x min(-1) after. The conduction block arrhythmia
      was happened in middle and high groups. The sodium currents of ventricular
      myocyte in mice was inhibited by urea(P < 0.05). The sodium currents amplitude
      value were reduced to (7.32 +/- 0.68, 5.69 +/- 0.64, 4.58 +/- 0.57) nA after
      using urea in each group and were (8.76 +/- 0.91, 8.87 +/- 1.01, 8.77 +/- 0.96)
      nA before, submit concentration dependent. CONCLUSION: Urea can inhibit the
      sodium currents of ventricular myocyte in mice to make it happen conduction block
      arrhythmia.

PMID- 21189559
TI  - [Endothelin-1 and nitric oxide mediated the lipopolysaccharide-induced cardiac
      negative inotropic role].
AB  - AIM: To investigate the effects of endothelin-1 (ET-1) and nitric oxide (NO) on
      lipopolysaccharide(LPS)-induced myocardial dysfunction, and explore the related
      underlying mechanisms. METHODS: Experimental septic model was established by
      intraperitoneal injection of LPS (10 mg x kg(-1)). The study was carried out on
      the isolated rat hearts to determine the roles of ET-1 and NO in the effect of
      LPS on the cardiac contractility and on the isolated rat ventricular myocytes
      model to observe the [Ca2+]i homeostasis in cardiac myocytes. RESULTS: (1) The
      levels of serum NO2-/NO3- and plasma ET-1 were markedly increased by LPS
      treatment for 4 hours. (2) LPS induced the decrease in rate-pressure product
      (RPP), and increase in left ventricular end-diastolic pressure (LVEDP) in the
      isolated perfused rat hearts. Pretreatment with either aminoguanidine (AMG) (100
      mg x kg(-1), i.p.) or BQ-123 (1 mg x kg(-1), i.p.) partially attenuated LPS
      induced myocardial depression. When these two drugs were simultaneously given,
      myocardial depression elicited by LPS was almost abolished. (3) LPS significantly
      decreased the amplitude of caffeine induced [Ca2+]i transients compared to the
      control cells. The activity of SR Ca22+ -ATPase was significantly decreased in
      the cardiac myocytes from LPS-treated rats. Single pretreatment with either AMG
      or BQ-123 did not attenuate the impairment of SR Ca2+ -ATPase induced by LPS.
      CONCLUSION: ET-1 and NO mediate myocardial dysfunction in hearts isolated and
      decrease [Ca2+]i transients in cardiac myocytes from LPS-treated rats. But
      neither ET-1 nor NO participates in the impairment of SR Ca2+ -ATPase induced by
      LPS.

PMID- 21189560
TI  - [Effect of stimulation of STN on the firing activities of the SNr neurons in
      rats].
AB  - AIM: To research the spontaneous firing activities during different-frequency
      stimulation of subthalamic nucleus and microelectrophoresis GABA, Glu and their
      antagons respectively, approaching the mechanism of DBS in the treatment of
      Parkinson's disease further. METHODS: Using extracellular recording to
      investigate the effect of different-frequency stimulation of STN and
      microelectrophoresis several drugs on the spontaneous firing activities of the
      SNr neurons. RESULTS: For STN stimulation at low frequency, there was no
      difference on the spontaneous firing activities of SNr neurons between pro
      stimulation and meta-stimulation (P > 0.05). With the increasing of stimulation
      frequency, most of the SNr neurons were inhibited. While during the STN
      stimulation frequency at high-frequency, the firing rates of inhibited SNr
      neurons were changed (P < 0.05). Glu had catatonic excitement effect on the SNr
      neurons, whereas GABA had tonic inhibition effect. 80% of SNr neurons which were
      inhibited by STN-HFS were not inhibited by STN-HFS on the basis of excitatory
      effect of BIC. CONCLUSION: To treat the motor symptoms of PD, when SIN is
      selected as the target nucleus, the electrical stimulation with high-frequency
      should be chosen. It is possible that SIN-HFS modulate the activity of SNr by
      inhibitory effect of GABA predominantly.

PMID- 21189561
TI  - [Proteomic analysis of myocardial hypertrophy induced by left kidney artery
      coarctation in rats].
AB  - AIM: To identify the expression of proteins in cardiomyocytes in rats with left
      kidney artery coarctation. METHODS: 16 male SD rats were separated into 2 groups
      (n=8): 2 kidney 1 Clip group (2K1C) and sham operation group (SO). The
      postoperational 8th week, after examination by normal doppler and tissue doppler
      echocardiography, the extracted proteins from cardiomyocytes were isolated by two
      dimensional gel electrophoresis with staining. The gel images were acquired by
      scanner and 2-DE analysis software. Different spots observed on two 2D gels were
      selected and identified by matrix-assisted laser desorption ionization time-of
      flight mass spectrometry (MALDI-TOF-MS). RESULTS: Overall, 21 protein spots
      showed significant difference, and 14 out of which were identified. CONCLUSION:
      Kidney artery coactation-induced cardiac hypertrophy displays different
      expression of proteins in cardiomyocytes.

PMID- 21189562
TI  - [Effect of Astragalus on lipid peroxidation injury with ischemia/reperfusion
      (I/R) of intestinal and the pathogenesis].

PMID- 21189563
TI  - [Construction and assessment of short-hairpin RNA eukaryotic expression vector
      targeting TGF-beta1 labeled by GFP].
AB  - AIM: To construct short hairpin RNA (shRNA) eukaryotic expression vectors
      targeting TGF-beta1 for further research on the effects of TGF-beta1 on
      vasculogenesis and angiogenesis. METHODS: Three pairs of siRNA target sequences
      coding from the mRNA of TGF-beta1 gene were designed and three pairs of
      nucleotides were synthesized. After annealing, the double-strand DNA products
      were ligated into the pEN_mH1c entry vector, and in turn into the shRNA
      eukaryotic expression vector pDS_hpEy labled by GFP through the LR recombination
      reaction. After sequencing successfully, the three resulting TGF-beta1 shRNA
      expression vectors were transfected into the mouse fibroblast cell line
      (NIH/3T3), and then cell clones stably expressing TGF-beta1 shRNA were screened.
      Reverse Transcript-Polymerase Chain Reaction (RT-PCR) and Western blot were used
      to detect the mRNA and protein expression. RESULTS: RT-PCR and Western blot
      showed that one of the TGF-beta1 shRNA expression vectors pDS_Tc downregulated
      TGF-pl mRNA and protein expression markedly in NIH/3T3 cells. CONCLUSION: ShRNA
      eukaryotic expression vectors targeting TGF-beta1 are successfully constructed
      which can be used for further investigation on the mechanism through which TGF
      beta1 regulates vasculogenesis and angiogenesis.

PMID- 21189564
TI  - [Effects of insulin-like growth factor-II on the TNF-alpha content of the
      hippocampus after ischemia/reperfusion injury following focal cerebral ischemia
      in rat].

PMID- 21189565
TI  - [The effects of safflower injection on lipid peroxidation level and expression of
      heme oxygenase-1 of the rat liver with hypoxia and hypercapnia].
AB  - AIM: To investigate the changes of lipid peroxidation level and expression of
      heme oxygenase-1 of the rat liver with chronic hypoxia and hypercapnia, and the
      effects of Safflower injection (a compond of Chinese Traditional medicine).
      METHODS: Thirty male SD rats weighing 180 approximately 220 g were divided into
      three groups (n=10): control group (N group), chronic hypoxia and hypercapnia for
      four weeks group(F group), and Safflower injection group (H group). SOD and MDA
      in liver tissue were measured by spectrophotometric method. And methods
      Immunohistochemical assay was used to detect the distribution of HO-1 protein.
      Pathological changes in liver tissues were observed in HE staining section. The
      mRNA expressions of HO-1 in liver were detected by semi-quantitative RT-PCR.
      RESULTS: The activity of SOD of the liver in F group were significantly lower
      than those in N group, and the content of MDA were significantly higher. The
      activity of SOD of the liver in H group were significantly higher than those in F
      group, and the content of MDA were significantly lower. In F group there were
      multiple dispersed immunoreactivity cells in liver. And compared to those in F
      group, the immunoreactivity cells were significantly decreased in H group. HE
      staining revealed that there were many hepatocytes with obvious adipose
      degeneration. Hepatic pathological damage in H group was slighter than that in F
      group. The expression of HO-1 mRNA of the liver in F group were significantly
      higher than those in N group (P < 0.01), and those in H group were significantly
      lower than those in F group (P < 0.01) . CONCLUSION: Chronic hypoxia and
      hypercapnia increases the level of oxidative stress. Safflower injection have a
      protective effect, maybe because of the accommodation of the expression of HO-1
      of the liver and the elimination of free radicals.

PMID- 21189566
TI  - [Oxidative stress induces apoptosis via NF-kappaB-iNOS-nitric oxide pathway in
      pancreatic beta-cells].
AB  - AIM: To explore the possible mechanism of tert-butyl hydroperoxide (t-BHP)
      induced apoptosis in murine MIN6 pancreatic beta-cells. METHODS: MIN6 cells were
      cultured in vitro. Cell damage was evaluated by epifluorescence microscopy after
      staining with AO-EB. The percentage of cell apoptosis was determined by flow
      cytometric assay after Annexin- V-PI staining. Nitric oxide levels were measured
      by Griess assay. Inducible nitric oxide synthase(iNOS) protein and NF-kappaBp65
      fragment were detected by Western blot. RESULTS: Exposure of 25 micromol/L t-BHP
      to MIN6 cells for 60 min, cell viability was reduced and the percentage of
      apoptosis was increased significantly. The levels of cytoplasmic iNOS protein and
      nitrite were elevated. Meanwhile, treatment with t-BHP resulted in nucleus NF
      kappaBp65 fragment peaking at 20 min. Both L-NAME and N-Acetyl-l-cysteine (NAC)
      attenuated the elevated levels of nitrite and percentage of apoptosis due to t
      BHP alone. CONCLUSION: NF-kappa-iNOS-nitric oxide signalling pathway can mediated
      t-BHP induced apoptosis in MIN6 cells .

PMID- 21189567
TI  - [Changes of rabbit IL-1 and TNF-alpha, etc cytokines in response to acute
      normovolemic hemodilution with HAES-balanced solution as diluting agent].
AB  - AIM: To observe effect of acute normovolemic hemodilution(ANH) with HAES-balanced
      solution as diluting agent on levels of cytokines including IL-1, IL-2, IL-6 and
      TNF-alpha in rabbit serum so as to provide theoretical basis for clinical
      application. METHODS: A total of 20 healthy adult rabbits were enrolled in the
      study and randomly divided into two groups (10 rabbits per group), i.e., control
      group (Group C) and HAES group (Group H). Under anesthesia of the rabbits, we
      performed incision of trachea, high-frequency jet ventilation and liberation of
      femoral artery and femoral veins. Group C was free from hemodilution. Group H was
      injected with dilution (2-fold of blood letting volume) via femoral veins during
      blood letting of the femoral artery. 6% HAES-steril plus compound solution of
      sodium lactate, with crystal/gel ratio of 2:1, blood letting volume = TBV x (Ho
      Hf)/Hav. All blood was transfused back 60-120 min after blood letting. Venous
      blood was collected before blood letting (T0) and 30 min (T1), 60 min (T2), 120
      min (T3) and 24 h(T4) after blood letting to detect Hb and Hct and measure level
      of IL-1, IL-2, IL-6 and TNF-alpha in serum. RESULTS: In Group H, levels of IL-1,
      IL-2, IL-6 and TNF-alpha in serum were increased from T1 after ANH, reached peak
      at T3 but showed decrease at T4, with significant difference compared with Group
      C at T1, T2, T3 and T4 (P < 0.01) and significant difference compared with those
      before ANH (P <0.01). In Group C, there was no significant difference upon IL-1,
      IL-2, IL-6 and TNF-alpha in serum at different time points. CONCLUSION: ANH with
      HAES-balanced solution as diluting agent can up-regulate the levels of cytokines
      IL-1, IL-2, IL-6 and TNF-alpha in rabbit serum. In the meantime, ANH may arouse
      eustress with low intensity and short action time, which exerts effect of
      enhancing immune function of the organisms.

PMID- 21189568
TI  - [iNOS and AChE expression on guinea pigs cochlea spiral ganglion induced by
      streptomycin and attenuation by Salvia miltiorrhiza injection].
AB  - AIM: To study the expression of iNOS and AChE on ginea pigs cochlea spiral
      ganglion induced by streptomycin (SM) and attenuation by salvia miltiorrhiza
      injection (Chinese Traditional medicine-dansen DS). METHODS: 32 guinea pigs were
      divided into 4 groups randomly (n=8): control group, SM group, DS + SM group, DS
      group. SABC immunohistochemical staining and image quantitative analysis
      technique were used to observe the expression of iNOS and AChE, as well as grey
      value analysis, and ABR measurements were used to observe ototoxicity. RESULTS:
      After 10 days with drugs, the ABR threshold value of SM increased more
      significantly than that of the control (P < 0.01), while the ABR threshold value
      of DS+ SM co-treatment increased than the control group, but lower than that of
      SM group (P < 0.01). The results of immunohistochemical staining implied the
      expression of iNOS and AChE in SG of SM group were higher than that of control
      group, and had positive correlate. CONCLUSION: The ABR threshold value increases
      and the expression of iNOS and AChE strengthen on SM ototoxicity, and has some
      correlation. DS can attenuate the ototoxicity induced by SM, and has protective
      function.

PMID- 21189569
TI  - [Effects of glutamine on the colon of mice subjected to colitis gravis].
AB  - AIM: To investigate the effects of glutamine on the colonic mucosa of mice
      subjected to colitis gravis. METHODS: 64 Kunming mice were divided randomly into
      4 groups (n=16): healthy group: animals not subjected to colitis; model group:
      animals subjected to colitis gravis but without glutamine supplementation; low
      Gln group: animals subjected to colitis gravis and with low dose of glutamine
      supplementation; high-Gln group: animals subjected to colitis gravis and with
      high dose of glutamine supplementation. Animals belonging to the control, the low
      Gln, the high-Gin groups were subjected to coloclysis by HAC to be colitis gravis
      animals. When the models were established, the healthy and the control groups
      were given some isotonic Na chloride by intragastric administration. The low-Gln
      group and the high-Gln group were given the same volume but different
      concentration of glutamine(low-Gln group--2 mmol x Kg(-1) bw, high-Gln group--2
      mmol x Kg(-1) bw) for 7 days. Then the mice were sacrificed, the
      pathohistological changes of the colon were observed, besides, the content of
      endotoxin in the blood serum, the level of counteracting oxidation and the
      activities of MPO of the colon tissue were determined. RESULTS: The glutamine
      lessened the pathological injures in the colon and relieved the step up of the
      content of endotoxin in the blood serum , the step down level of counteracting
      oxidation and the step up activity of MPO in the colon tissue, which were caused
      by colitis gravis. CONCLUSION: The glutamine can protect the colon of mice
      subjected to colitis gravis.

PMID- 21189570
TI  - [Involvement of leukotrine B4 receptors in the inflammatory responses and
      immunological regulation in vitro].
AB  - AIM: BLT1 and BLT2 were both recently cloned and identified as two subtypes of
      leukotrine B4 (LTB4) receptors. With the usage of U-75302 and LY255283, the
      specific antagonists of BLT1 and BLT2 respectively, the involvement of BLT1 and
      BLT2 in the inflammatory and immunological responses was in vitro explored.
      METHODS: (1) To investigate inhibition of U-75302 and LY255283 on the
      proliferation of rat synovial cells, 3H-TdR incorporation into the cells was
      quantified. (2) Flow cytometric assay for interferon-gamma (IFN-gamma) and
      interleukine 4 (IL-4) profiles in CD4+ T lymphocytes from rat spleen was carried
      out to determine the ratio of Th1/Th2. RESULTS: (1) For inhibition on rat
      synovial cells proliferation, U-75302 exerted its effect only at a high
      concentration of 10 micromol/L and LY255283 at the concentrations of 10
      micromol/L-10 micromol/L. (2) Both U-75302 and LY255283 could elevate the
      percentage of Th2, but could not influence that of Th1. CONCLUSION: BLT1 and BLT2
      were involved in the synovial cells proliferation change the ratio of Th1/Th2.
      Their meaning served as targets for prevention and treatment of infectious
      diseases should be emphasized.

PMID- 21189571
TI  - [Effects of p38 mitogen-activated protein kinase in protection of carbon monoxide
      against lipopolysaccharide induced rat small intestine injury].
AB  - AIM: To investigate the effects of low concentration carbon monoxide (CO)
      inhalation or intraperitoneal infusion on lipopolysaccharide (LPS) induced rat
      small intestine injury and to detect the roles of p38 mitogen-activated protein
      kinase (MAPK) pathway during CO administration. METHODS: SD rats with small
      intestine injury induced by 5 mg/kg LPS intravenous injection were challenged by
      room air, 2.5 x 10(-4)(V/V) CO inhalation or intraperitoneal infusion for 1 h, 3
      h and 6 h differently. Then all animals were sacrificed, and the ileum tissues
      were homogenized for determination the levels of platelet activator factor(PAF)
      and intercellular adhesion molecule-1 (ICAM-1) with enzyme-lined immunosorbent
      assay, the pathology with light microscope, and the phosphorylated p38 MAPK
      expression with Western blot. RESULTS: Compared with either control, CO
      inhalation or intraperitoneal infusion group at the same time point, the levels
      of PAF, ICAM-1 and the phosphorylated p38 MAPK of LPS group were increased (all P
      < 0.01), but there were no statistics differences at the different time point of
      this group. PAF and ICAM-1 in both LPS injection + CO inhalation group and LPS
      injection + CO intraperitoneal infusion group were significantly lower than the
      corresponding value in LPS injection group at the same time point (all P < 0.05),
      while the expression of phosphorylated p38 MAPK was further up-regulated than
      that of LPS injection group (P < 0.05). However, there were no significant
      differences in these parameters between LPS injection+ CO inhalation group and
      LPS injection+ CO intraperitoneal infusion group. CONCLUSION: Low concentration
      CO inhalation and intraperitoneal infusion exerts the similar protection against
      LPS induced rat small intestine injury via down-regulating PAF and ICAM-1
      expression. This may involve the p38 MAPK pathway.

PMID- 21189572
TI  - [The significance of NO in renal cell apotosis following hind limbs
      ischemia/reperfusion in rats].

PMID- 21189573
TI  - [The new method of cells growing on the glass slide].
AB  - AIM: To improve the method of cell growing on the glass slide. METHODS: Cells
      were planted in a system making by 1 ml tips and slide. RESULTS: Cells grow on
      the slide directly , no pollution and well proliferation, was fewer dropped off
      the slide than the traditionary method. CONCLUSION: The improved method had the
      advantages including easy-material, low-price, well-effect and convenient
      operation , and prior to the traditionary method.

PMID- 21189574
TI  - [The proliferation profile of mouse spermatoganial stem cells in three types of
      culture media].
AB  - AIM: To establish an in vitro long-term culture system of mouse Spermatogonial
      stem cells (SSCs). METHODS: Three types of serum-free culture media, namely,
      DMEM/F12, KSR (KnockoutM Serum Replacement) and StemPro-34 SFM, to which the same
      growth factors including GDNF, soluble GFRalpha1 and bFGF were added equally, and
      MEF(mouse embryonic fibroblast) feeder layer were used to culture mouse SSCs
      enriched from pup mice testes through differential adherence selection. The
      activity of stem cells was examined morphologically, and the marker gene
      expression of SSCs was detected by RT-PCR and immunocytochemical analysis.
      RESULTS: The activity of SSCs cultured in DMEM/F12 and KSR serum-free media was
      only maintained for 6-7 days. However, the StemPro-34 SFM medium could maintain
      the proliferation of cultured SSCs nearly one month. CONCLUSION: StemPro-34 SFM
      serum-free medium sustains the proliferation of mouse SSCs in vitro.

PMID- 21189575
TI  - [Effects of Angelica sinensis injection on the neuronal metabolites and blood
      flow speed within reperfusion following the ischemic cerebral injury in rats].
AB  - AIM: To investigate the effects of Angelica sinensis injection on the neuronal
      metabolites and blood flow speed within reperfusion in the ischemic cerebral
      injury of rats. METHODS: Sixty-nine male Sprague Dawley rats with an average body
      weight of 150 to 170 g were used, and were randomly divided into three groups:
      sham operation group (n = 4), ischemia injury group (n = 30) underwent an
      operation of ischemic brain injury, Angelica-treated group (n = 35) underwent the
      same operation and received the treatment of Angelica sinensis injection (5 g/kg
      bw, i. p). The right middle cerebral artery occlusion (MCAO) of both ischemia
      injury group and Angelica-treated group rats was induced by 5/0 nylon suture for
      2 hours. The reperfusion was conducted for three to four hours and five to six
      hours respectively following MCAO. T2 weighted-imaging (T2WI) and 1H magnetic
      resonance spectroscopy (1H MRS) were performed, to study the changes in imaging
      and neuronal metabolites N-acetyl aspartate (NAA), creatine/phosphocreatine (Cr/
      PCr) and choline (Cho) following cerebral ischemia. The changes in blood flow
      speed were measured by laser Doppler flowmetry. The surface vascular density in
      right hemisphere were calculated. RESULTS: The hyperintense signals and volume in
      the right cerebrum in Angelica-treated group decreased compared with those of the
      ischemia injury group, the T2 values were decreased, and the level of NAA
      increased, the ratio of Cr/NAA and Cho/NAA decreased. The blood flow speed in
      Angelica-treated group was improved. The length of brain surface vessels in group
      C increased. CONCLUSION: The Angelica sinensis injection enhanced the blood
      circulation in the ischemic brain, improved the neuronal metabolisms.

PMID- 21189576
TI  - [Influence of astragalus and zinc sulfate on the viscosity in erythrocyte
      membrane during intestinal ischemia - reperfusion(I/R) injury].
AB  - AIM: To study the influence of astragalus and zinc sulfate on the viscosity in
      erythrocyte membrane during intestinal I/R and their mechanism of action.
      METHODS: Models of rabbits intestinal I/R injury were made. The effect of
      astragalus and zinc sulfate on the viscosity and malondialdehyde (MDA) in
      erythrocyte membrane, superoxide dismutase (SOD) in erythrocyte, oxidase (XO) in
      plasma and MDA tissues homogenate were observed. RESULTS: The administration of
      astragalus and zinc sulfate decreased viscosity and MDA and XO, prevented the
      reduction of SOD, and alleviated I/R injury. CONCLUSION: Lipid peroxidation
      injury of the erythrocyte membrane was one of the pathogenesis of I/R injury, and
      astragalus and the zinc sulfate possessed effects of anti-lipid peroxide,
      stabilized erythrocyte membrane, increased red blood cell deform ability and
      raised microcircular perfusion.

PMID- 21189577
TI  - [Effects of stress on L type calcium channels of rat ventricular myocytes].
AB  - AIM: To observe the effects of stress on Ica-L, steady-state activation curves
      and steady-state inactivation curves. METHODS: Use NE to construct stress cell
      model, then the whole-cell patch-clamp recording technique was used to record the
      Ica-L, the steady-state activation curves and the steady-state inactivation
      curves. With FCM technique, we observed the rate of apoptosis of cardiomyocytes.
      By dying cells with Fura-2 and fluorometry, we determined [Ca2+]i. RESULTS: The
      amplitude of peak current of Ica-L increased significantly, and by analyzing the
      steady-state activation curve, we found that the curve was shifted to left, the
      V1/2 of stress group was (-14.59 +/- 0.24 ) mV vs (-0.69 +/- 0.36) mV of control
      group. The rate of apoptosis was increased from 0.36% to 2.17% (P < 0.01). The
      [Ca2+]i increased by 16.7%. CONCLUSION: Stress can bring on increasing of Ica-L,
      and the channels are easy to be activated. These changes can cause "calcium
      overload" and then induce apoptosis which lead to injury of myocytes in stress.

PMID- 21189578
TI  - [Effect of NADPH-cytochrome C reductase on iodine organification].

PMID- 21189579
TI  - [The influence of dehydrocorydaline on intracellular free calcium concentration
      during hypoxia in myocardial cell of guinea-pigs].
AB  - AIM: To study the effect of Dehydrocorydaline and Verapamil (Ver) on
      intracellular free calcium concentration of myocardial cell ([Ca2+]i) under
      hypoxic condition. METHODS: We adopted guinea-pig heart Langendorff instillation.
      The myocardial cells were isolated by collagenase (Type I, sigma)and marked by
      fluorescence ratio imaging. The suspension of myocardial cells was assigned to
      six groups: DHC, Ver, and control were each two. Each three groups was exposed to
      hypoxia and normoxia before determination of [Ca2+]i. RESULTS: (1) In normoxia
      state, [Ca2+]i was 120.5-8.3 nml/L (n = 20).( 2) In hypoxia state, the increased
      [Ca2+]i of myocardial cells was proportional to the time (degree) of hypoxia.
      Correlation coefficient (r) was about 0.98. (3) Under the condition of normoxia
      DHC and Ver decreased [Ca2+]i. (4) DHC was obviously slow the increase of [Ca2+]i
      after hypoxia. CONCLUSION: In normoxia and hypoxia, DHC decreases the increased
      [Ca2+]i. It can prevent intracellular calcium overload. We believe DHC may
      improve self-protected performance of myocardial cells.

PMID- 21189580
TI  - [Effect of human chorionic gonadotrophin on the expression of tissue inhibitor of
      metalloproteinases (TIMPs) in choriocarcinoma cell line].

PMID- 21189581
TI  - [The effects of cell growth factors on proliferation and migration of coronary
      artery endothelial cells].
AB  - AIM: To study the effects of hepatocyte growth factor (HGF) and vascular
      endothelial growth factor (VEGF) on proliferation and migration of bovine
      coronary artery endothelial cells (BCAEC) in vitro. METHODS: BCAECs were isolated
      and cultured in vitro, and divided into control group, VEGF group and HGF group.
      BCACEs proliferation were measured using MTT, and their migration was observed
      using reverse microscope. RESULTS: The OD value of control, VEGF and HGF group
      were 0.22 +/- 0.01, 0.40 +/- 0.14, 0.44 +/- 0.15 respectively. The proliferation
      ratio of BCAECs in VEGF and HGF group was 81.8% +/- 16.9%, 100.0% +/- 21.1%
      respectively. There was no migration in control group, but significant migration
      in VEGF and HGF group. CONCLUSION: Both VEGF and HGF can promote proliferation
      and migration of BCAECs, the effect of HGF is stronger than VEGF.

PMID- 21189582
TI  - [A study of the effect of PTEN on cardiac hypertrophy].
AB  - AIM: To investigate the role of tumor suppressor PTEN in cardiac hypertrophy, the
      expression of PTEN mRNA in left ventricle of abdominal aorta constricted-induced
      cardiac hypertrophic rats which treated with and without captopril was analyzed.
      METHODS: SD rats were divided into control group, hypertrophy group and captopril
      group. The expression of PTEN mRNA in left ventricle was detected by RT-PCR in
      different groups in 4 weeks after operation. RESULTS: (1) Compared with control
      group, the expression of PTEN mRNA in left ventricle of hypertrophy group was
      reduced. (2) Compared with hypertrophy group, the expression of PTEN mRNA in left
      ventricle of captopril group was upregulated, which were similar to that of
      control group. CONCLUSION: PTEN maybe plays a negative regulation role in the
      process of cardiac hypertrophy, and the role of PTEN is closely relative with
      renin-angiotensin system.

PMID- 21189583
TI  - [Effect of substance K on the contractility of cardiomyocytes].
AB  - AIM: To investigate the influence and the mechanism of SK on the contractility of
      cultured cardiomyocytes of rats. METHODS: The primary cultured single myocardial
      cell was treated with SK and the contraction frequency and size of cardiomyocyte
      were determined by a computer image analysis system. At the same time the effects
      of propranolol (a beta receptor antagonist), phentolamine (a alpha receptor
      antagonist), DSP (a tachykinin receptor antagonist) on the action of SK were
      investigated. RESULTS: SK increased contractive extend of the cardiomyocyte, in
      which a dose-response relationship of SK at 1.78 x 10(-8) - 1.78 x 10(-5) mol/L
      exists. But the frequency of contraction did not change, pretreatment with
      propranolol, phentolamine had no action on the effect of SK, but DSP markedly
      attenuated the effects of SK. CONCLUSION: SK may directly enhance the
      contractility of single cardiomyocyte, which may be related with the tachykinin
      receptor.

PMID- 21189584
TI  - [The change of adrenergic receptor-adenyl cyclase system on myocardial ischemic
      preconditioning in rats].
AB  - AIM: To study the varies and effects of ischemic preconditioning of myocardium on
      every part of adrenergic receptor-adenyl cyclase system in rats in vivo. METHODS:
      SD rats were randomly divided into three groups: CON group (n = 6), IP group (n =
      12) and I/R group (n = 12). Surgical procedure included intermittent left
      coronary artery occlusion and reperfusion. After the procedure, the hearts were
      extracted. We analyzed the infarct size by TTC staining, measured serum
      myocardial enzymes, studied the beta-AR Bmax and KD by radioligand binding assay
      of receptors (RAB), and checked the activity of AC and the content of cAMP by
      radioimmunoassay (RIA). RESULTS: Infarct area were much smaller in IP group than
      in I/R group (P < 0.05). CK, CK-MB, LDH were significantly higher in I/R group (P
      < 0.01). The Bmax of beta-AR in IP group were much higher than in I/R group (P <
      0.01). No difference of KD could be seen between IP and I/R group. In IP group,
      the activity of AC and the content of cAMP were higher than I/R group (P < 0.05).
      CONCLUSION: Ischemic preconditioning can protect the heart from necrosis and
      reduce endo-enzyme leakage. Ischemic preconditioning can increase the density of
      beta-AR, the activity of AC and the content of cAMP, which shows that the system
      of adrenergic receptor-adenyl cyclase system probably takes part in the
      protection of IP.

PMID- 21189585
TI  - [Effects of ginkgolide (Gin) on cerebral water content, Na+, K(+) -ATPase
      activity, MDA, lactic acid of rats during acute hypoxia condition].

PMID- 21189586
TI  - [Change of enzyme activity correlation with nucleic acid metabolism during the
      vascular intimal hyperplasia].
AB  - AIM AND METHODS: To determine the relationship between the nuclear envelope
      nucleoside triphosphatase (EC 3. 6. 1. 15, NTPase) activity and the phenotypic
      modulation of vascular smooth muscle cell (VSMC), the NTPase activity was
      detected during restenosis after de-endothelialization in vascular wall. The
      activities of three enzymes involved in carbohydrate and nucleic acid metabolism
      were also investigated by spectrophotometry. RESULTS: The activity of NTPase
      increased continuously and associated with the process of intimal thickening.
      Western blotting showed that expression of SMalpha-actin, as the marker of
      contractile phenotype of VSMC, decreased continuously. Osteopontin (OPN), the
      marker of synthetic phenotype of VSMC, was up-regulated during the process. These
      suggested that intimal injury induced phenotypic modulation of VSMC. The
      activities of 5'-nucleotidase, adenosine deaminase and succinate dehydrogenase
      increased and reached their peaks on 7 days after de-endothelialization. The
      changes of three enzymes were associated with proliferation in VSMC. CONCLUSION:
      The efflux of mRNA and the changes of enzyme activity involved in carbohydrate or
      nucleic acid metabolism may be the biochemical basis in the development and
      progression of restenosis.

PMID- 21189587
TI  - [Effects of lidocaine and thiopental on the neuronal injury in rat hippocampus
      slice cultures].
AB  - AIM: To observe the effects of lidocaine and thiopental on the neuronal injury
      induced by the experimental ischemia in hippocampus slice cultures obtained from
      postnatal 22 days SD rats. METHODS: Model of the experimental ischemia was
      produced by hypoxia and glucose deprivation. Propidium iodide (PI) assay was used
      to observe the neuronal injury in CA1 and dentate gyrus (DG). RESULTS: After
      experimental ischemia, the peak of PI index was appeared in CA1 and DG on the
      first day (P < 0.01), PI index in DG was less than in CA1 (P < 0.01). PI indices
      were still higher during seven days after the experimental ischemia than before
      the experimental ischemia (P < 0.01). 10 nmol/L and 100 nmol/L concentration of
      lidocaine could significantly decrease PI indices in CA1 and DG (P < 0.01). 250
      nmol/L and 600 nmol/L concentration of thiopental also decreased the PI indices
      in CA1 and DG (P < 0.01). The neuronal injury peaks were postponed to the third
      day after the experimental ischemia by lidocaine and thiopental. CONCLUSION: It
      suggested that lidocaine and thiopental could decrease the neuronal injury in CA1
      and DG induced by the experimental ischemia, and postpone the neuronal injury
      peaks to the third day after the experimental ischemia.

PMID- 21189589
TI  - [Effect of CoCl2 pretreatment on Na + and K+ currents of the rat hippocampal
      neurons after acute hypoxia].
AB  - AIM: To study effect of CoCl2 pretreatment on the voltage-gated Na+ and K+
      currents of the rat hippocampal neurons after acute hypoxia. METHODS: Primarily
      cultured hippocampal neurons were divided into CoCl2 pretreated and non
      pretreated groups. Patch clamp whole cell recording technique was used to examine
      Na+ and K+ currents of the hippocampal neurons. RESULTS: After acute hypoxia,
      I(Na) and I(K) of the hippocampal neurons were significantly decreased and the
      threshold of I(Na) was right-shifted. Pretreatment of the neurons with CoCl2
      inhibited the reduction of I(Na) and I(K). CONCLUSION: CcCl2 pretreatment
      alleviates the acute hypoxia-induced changes of I(Na) and I(K), which may be one
      of the mechanisms for the protective effect of CoCl2 on neurons.

PMID- 21189590
TI  - [Effect of corticosterone on the delayed rectified potassium currents of cultured
      rat hippocampal neurons in vitro].
AB  - AIM: The effect of stress hormone corticosterone on hippocampal neurons delayed
      rectified potassium currents was probed. METHODS: The potassium currents of rat
      hippocampal neurons in primary culture were measured with patch clamp whole-cell
      recording. RESULTS: It showed that the amplitudes of the potassium currents in
      hippocampal neurons decreased. However, the threshold potential of potassium
      currents increased. CONCLUSION: It is speculated that excessive corticosterone
      may hurt the hippocampal neurons via its effects on the potassium currents of rat
      hippocampal cells.

PMID- 21189591
TI  - [Effects of visceral malaise on the different taste solutions in-take].

PMID- 21189592
TI  - [Membrane electrical properties of visceral nociceptive neurons in anterior
      cingulate gyrus of cat].
AB  - AIM: To explore the cerebral cortex mechanism of visceral nociceptive sensation
      and its characteristics on the cell level, we investigated the membrane
      electrical properties of 176 stimulus-relative neurons of greater splanchnic
      nerve (GSN) in anterior cingulate gyrus (ACG) of 20 adult healthy cats. METHODS:
      We used intracellular recording techniques of glass microelectrode and injected
      polarizing current into the neurons in ACG. RESULTS: Among 176 neurons, 148 were
      visceral nociceptive neurons (VNNs) and 28 non-visceral nociceptive neurons
      (NVNNs). The membrane resistance (Rm), time constant (tau), membrane capacity
      (Cm), and the I-V curve of both VNNs and NVNNs in ACG were significantly
      different. The discharge frequency and amplitude of both VNNs and NVNNs produced
      by injecting depolarized current were different, too. CONCLUSION: The results
      suggest that structure of cell membrane, volume of the soma, and other aspects of
      morphology between VNNs and NVNNs in ACG may have significant differences. The
      results also might provide progressively experimental evidence for specific
      theory of pain sensation.

PMID- 21189593
TI  - [Effects of central and peripheral administration of a nitric oxide synthase
      inhibitor on AVP-induced hypothermia in rats].
AB  - AIM: To explore the role of nitric oxide (NO) in arginine vasopressin (AVP)
      induced hypothermia. METHODS: Colonic temperature was measured at 30 min
      intervals with a digital thermometer. Effects of central and peripheral
      administration of nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine
      methyl ester (L-NAME) on AVP-induced hypothermia were observed in rats. RESULTS:
      (1) Intravenous injection (i.v.) of AVP (4 microg x kg(-1)) and L-NAME (30 mg x
      kg(-1)) produced a significant drop in body temperature, respectively.
      Coadministration of L-NAME i.v. with AVP i.v. did not significantly influence the
      magnitude of AVP-induced hypothermia. (2) Intracerebroventricular (i.c.v.)
      injection of L-NAME (1 mg x kg(-1)) caused a significant increase in body
      temperature, but when the treatments with AVP and L-NAME were combined, i.c.v.
      injection of L-NAME markedly blocked the hypothermic effect of AVP intravenous
      injection. CONCLUSION: Endogenous NO in the central nervous system plays a major
      role in AVP-induced hypothermia. In addition, central NO seems to play a tonic
      thermoregulatory role by reducing normal body temperature because an increase in
      body temperature was observed after treatment with NOS inhibitor L-NAME.

PMID- 21189594
TI  - [The effect of interleukin-1 on the expression of CD62p in human umbilical vein
      endothelial cell line EA. hy926].

PMID- 21189595
TI  - [The relation between amygdaloid nucleus in rats and pain modulation].
AB  - AIM: To research the influence of noxious stimuli on the electric activities of
      pain-related neurons in several subnuclei of Amygdaloid Nucleus in rats. METHODS:
      Trains of the electric impulses applied to the sciatic nerve were used as noxious
      stimuli. The discharges of neurons were channeled off by glass microelectrode.
      RESULTS: Pain-related neurons existed in several subnuclei of Amygdaloid Nucleus.
      When the noxious stimuli were administered the frequency of discharges of pain
      excited neurons (PEN) was increased while the frequency of pain-inhibited neurons
      (PIN) was decreased to the lowest level. The electric activities of PEN and PIN
      were matched with each other. Intraperitoneal injection of morphine (10 mg/kg)
      antagonized the effects of noxious stimuli on the pain-related neurons.
      CONCLUSION: Several subnuclei of Amygdaloid Nucleus play an essential role in
      perceiving, integrating and transmitting the pain impulses. They are a part of
      the central nervous system in which pain information is controlled and managed.

PMID- 21189596
TI  - [The effects of simulated microgravity on pulmonary arteries and aortae].
AB  - AIM: Through studying local regulatory mechanisms in pulmonary arteries (PA) and
      thoracic aortae (TA) under simulated microgravity (SM), to collect some data for
      the researches of adaptive mechanisms in pulmonary and systemic arteries and for
      the mechanisms accounting for orthostatic intolerance after SM. METHODS:
      Cardiopulmonary circulatory function during 7-day 6 degrees head down bed rest
      (HDT) in male young volunteers was measured with a XXH-2000 pulmonary circulation
      and cardiac function instrument. - 30 degrees C tail suspended (TS) rats were
      used as the model to simulate the physiological effects of M. The PA and TA
      changes of vasoreactivity were respectively observed by vitro vessel rings
      perfusion. RESULTS: The changes in volume of PA and pulmonary vein during a
      cardiac cycle and the preload in left cardiac ventricle in men increased
      significantly in the initial HDT. The super-regulatory phenomena appeared in both
      pulmonary and systemic circulation, but earlier and more obviously in pulmonary
      circulation than systemic circulation during 96-144 h. The dilatory reactivity in
      TS7 PA increased significantly, tended to decrease in TS14. The dilatory
      reactivity of TA in TS7 had a significant increase, had a slight increase in
      TS14. The contractile reactivity of PA decreased slightly in TS7 from CON, and
      were attenuated significantly in TS14. The contractile reactivity of TA in TS14
      decreased significantly. The responsiveness to KCl, phenylephrine and sodium
      nitroprusside in VEC- removed PA had no differences among all groups. CONCLUSION:
      The differences in changes between pulmonary and systemic arteries under SM could
      be an important sign of depressed local regulatory function, which might be
      mainly due to dilatory function in VEC and contribute to the occurrence of
      orthostatic intolerance after SM.

PMID- 21189597
TI  - [Impact of high pulmonary blood flow on pulmonary vascular structure and human
      urotensin II in intrapulmonary arteries of rats].
AB  - AIM: To study human urotensin II (hUII) expression in intrapulmonary arteries of
      rats with pulmonary hypertension induced by high pulmonary blood flow and explore
      the role of hU II in the development of pulmonary hypertension induced by left to
      right shunt. METHODS: Aortocaval shunting was produced for 11 weeks in rats.
      Pulmonary artery mean pressure (PAMP) of each rat was evaluated using right
      cardiac catheterization. The pulmonary vascular structural changes, including the
      percentage of muscularized arteries of small pulmonary vessels and relative
      medial thickness of intra-acinar pulmonary arteries were examined. Meanwhile, the
      expression of hU II by pulmonary arteries was detected by immunohistochemistry.
      RESULTS: After 11-week aortocaval shunting, PAMP was significantly increased. The
      percentage of muscularized arteries of small pulmonary vessels and relative
      medial thickness of pulmonary arteries were obviously increased in shunting rats
      compared with controls (P < 0.01, respectively). Meanwhile, hU II expression by
      pulmonary artery endothelial cells and smooth muscle cells was significantly
      augmented in rats of shunt group, which was positively correlated with PAMP and
      the structural changes in pulmonary arteries. CONCLUSION: The up-regulation of hU
      II in pulmonary arteries might be involved in the development of pulmonary
      vascular structural remodeling and pulmonary hypertension induced by high
      pulmonary blood flow.

PMID- 21189598
TI  - [Preliminary study on in vivo whole cell recording technique in anesthetized
      rat].

PMID- 21189599
TI  - [Experimental study on antagonism of tetrandrine in acute renal injury induced by
      gentamicin in guinea pig].
AB  - AIM: To investigate the antagonism of tetrandrine in acute renal injury induced
      by gentamicin in guinea pig. METHODS: The experimental guinea pigs are divided
      into 4 groups by randomized blocks, they were group 1 (control), group 2
      (tetrandrine), group 3 (gentamicin) and group 4 (gentamicin with tetrandrine).
      After 10 days, set apart urinary specimen for determination the activity of NAG,
      reserve renal specimen for observing the renal histology and measuring expression
      of actin and TGF-beta1. RESULTS: The renal histology showed that the injury of
      group 3 was the most grievous, group 4 was lighter than group 3. In addition, the
      apoptosis was obviously less than group 3. The activity of urine of NAG in group
      4 was lower than group 3. The levels of expression of actin and TGF-beta1 in
      group 4 were more than group 3. CONCLUSION: When kidney is damaged by gentamicin,
      tetrandrine is able to reduce the activity of urinary NAG and inhibit the renal
      tubular epithelial cell apoptosis. Besides, tetrandrine can prevent breaking
      actin and evoke the endogenous transmission growth factor beta1 tune-up, the
      above results can indicate that tetrandrine has antagonism to acute renal injury
      induced by gentamicin in guinea pig.

PMID- 21189600
TI  - [The effect of changing body posture on thrombin activity and concentration].
AB  - AIM: To provide proof for Evidence-based Medicine as well quality control, our
      laboratory detected the thrombin activity on various body position. METHODS: By
      autogenous contrast and cross matched survey, 105 volunteers divided into 3
      season patches of winter, spring and summer, blood samples were drawn from the
      same part in both standing and lying position. Both samples and the quality
      control were detected to investigate the effect of the body position to thrombin
      activity's changing. The data were analyzed by SPSS 10.0. RESULTS: Taking the
      lying's data as baseline, the average changing on all those the "5" index was
      7.07% and the highest changing reached 9.33%. This kind changing had great
      significant differences (P < 0.01). According to the t value, sequences ranged:
      FIB > TT > PT > INR > APTT. FIB, TT and APTT's values slowly raised, adversely PT
      and INR slowly went down. While sitting for 15 min after lying, these indices
      returned to 95.2% of the original value in sitting position in addition. Season,
      age and device had no relationship with body position. CONCLUSION: Changing body
      position can result in obvious physiological variation of thrombin activity.

PMID- 21189601
TI  - [Relative study for +Gz protection of an advanced bladder anti-G system and that
      of capstan anti-G system].
AB  - AIM: To assess the +Gz protection afforded by an advanced bladder anti-G system
      in the centrifuge against a capstan anti-G system. METHODS: Tow centrifuge
      experiments were completed, respectively, by two groups of six male subjects. In
      the first experiment, subjects using advanced bladder anti-G system, the +Gz
      protection afforded by this anti-G system was determined. Then they were exposed
      to simulated air combat maneuver (SACM)I with leg straining, the +Gz-time
      tolerance was determined. In the second experiment, subjects using capstan anti-G
      system, the +Gz protection afforded by this anti-G system was determined. Then
      they were exposed to SACMII with anti-G straining maneuver, the +Gz-time
      tolerance was determined. RESULTS: The anti-G effectiveness of the advanced
      bladder system was 5.33 G, which was significantly higher than that of the
      capstan system by 1.35 G (P < 0.01). All subjects of the two groups passed
      themselves SACM, but the effort, fatigue, and heart rates of the first group
      subjects were lower than those of the second group subjects. CONCLUSION: The
      results demonstrate that the +Gz protection afforded by the advanced bladder anti
      G system is significantly higher than that by the capstan system.

PMID- 21189602
TI  - [The quantitative changes of serum response factor in myocardium of patients with
      heart failure].

PMID- 21189603
TI  - [Glucocorticoids up-regulate human chorion 11beta-hydroxysteroid dehydrogenase
      type 1].
AB  - AIM: To study the co-localization of glucocorticoid receptor and 11beta
      hydroxysteroid dehydrogenase 1 (11beta-HSD1) and to investigate whether
      glucocorticoids regulate the reductase activity and expression of 11beta-HSD1.
      METHODS: Immunohistochemical staining for 11beta-HSD1 in cultured primary human
      chorionic trophoblasts was performed. Radiometric conversion assay and Northern
      blot analysis were respectively used to observe the activity and mRNA expression
      of 11beta-HSD1. RESULTS: 11beta-HSD1 and GR were co-expressed in the same
      chorionic trophoblast. Both 11beta-HSD1 reductase activity and mRNA levels were
      increased by dexamethasone (10(-6) mol/L, 10(-7) mol/L) in the cultured chorionic
      trophoblasts, and the effects were blocked by GR antagonist RU486 (10(-6) mol/L).
      CONCLUSION: By binding to GR, glucocorticoids induce the expression of 11beta
      HSD1 by a possible intracrine mechanism.

PMID- 21189604
TI  - [Effects of serum testosterone level on plasma lipid and apolipoprotein spectrum
      in orchiectomized rabbits].
AB  - AIM: To investigate the effects of serum testosterone level on plasms lipid and
      apolipoprotein spectrum in orchiectomized rabbits. METHODS: 40 male New Zealand
      rabbits were divided randomly into five groups (n = 8): control group, sham
      (castration), castration group (castration), hypotestosteronemia group
      (castration plus low dose testosterone replacement), physiological level group
      (castration plus moderate testosterone replacement), and hypertestosteronemia
      group (castration plus large dose testosterone replacement). The rabbits in
      hypotestosteronemia, physiological level and hypertestosteronemia group were
      injected testosterone undecanoate 3 mg/kg, 6 mg/kg, and 12 mg/kg, respectively
      and the remaining control, and castration rabbits, vehicle only. 8 weeks after
      initiation of the experiment, blood was collected for determination of serum
      levels of total testosterone (TT), estradiol (E2), lipids, lipoproteins,
      apolipoproteins. RESULTS: After castration, the serum level of TT decreased
      significantly to the lowest level, and TU replacement increased serum TT level
      depending on dose. The low dose of TU increased serum TT level slightly and
      produced a hypotestosteronemia model, the moderate dose of TU increased serum TT
      level near to normal level and produced a physiological model, the large dose of
      TU increased serum TT level significantly to the highest level and produced a
      hypertestosteronemia model. The tatol cholesterol (TC), triglycerides (TG), low
      density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB) were
      significantly increased in hypotestosteronemia and hypertestosteronemia rabbits
      and significantly decreased in physiological serum testosterone rabbits.
      CONCLUSION: Testosterone, at physiological level has good effect on the serum
      lipids, lipoproteins, apolipoproteins in the castration rabbits, and the
      hypotestosteronemia and hypertestosteronemia has bad effect.

PMID- 21189605
TI  - [Effect of peroxisome proliferator-activated receptors activators on plasminogen
      activator inhibitor-1 expression in HepG-2 cells].
AB  - AIM: To investigate the effect of different peroxisome proliferator-activated
      receptors (PPARs) activators on plasminogen activator inhibitor-1 in HepG-2 cell
      line and explore the effect of PPARs on PAL-1 gene expression. METHODS: Stearic
      acid, oleic acid, linoleic acid, fenofibrate, pioglitazone were used in the
      treatment of HepG-2 cell culture. The level of PAI-1 and PPARs mRNA was measured
      by reverse transcription-polymerase chain reaction (RT-PCR) and the level of PAI
      1 activity and PPARs protein was determined by colorimetric assay and western
      blotting respectively. RESULTS: The mRNA and activity of PAI-1 significantly
      increased in the groups of oleic acid and linoleic acid compared with the
      control, but decreased in the group of fenofibrate. There were no significant
      changes in both groups of stearic acid and pioglitazone. The alterations in the
      level of PPARs mRNA and protein were not detected in all the treated groups
      compared with the control. CONCLUSION: Peroxisome proliferator-activated
      receptors activators play important roles in the PAI-1 gene expression and
      regulation. It is likely mediated by the activation of PPARalpha, but there might
      be other mechanisms.

PMID- 21189606
TI  - [Experimental study on the effect of ginkgo bioba extract on the expression of
      heme oxygenase-1 in bronchial asthma].
AB  - AIM: To explore the effect of the ginkgo bioba extract on the expression of heme
      oxygenase-1 (HO-1) in bronchial asthma. METHODS: 30 guinea pigs were randomly
      divided into 3 groups (n = 10): (1) Normal control group; (2) Asthmatic group;
      (3) Therapeutic group. Blood carbon monoxide Hb (COHb) percent value, Airway
      resistance and eosinophilic inflammation of airway wall were observed, the
      expression of HO-1 in lung tissue were observed by immunohistochemical staining.
      RESULTS: The expression of HO-1 was mainly located in airway epithelium in these
      3 groups, the optical densities were 0.170 +/- 0.020, 0.707 +/- 0.058, 0.397 +/-
      0.034, respectively. The asthmatic group showed higher optical densities than
      that of the normal control group (P < 0.01), and the therapeutic group showed
      lower optical density than asthmatic group (P < 0.01). CONCLUSION: The expression
      of HO-1 is inhibited significantly by the treatment of the ginkgo bioba extract,
      which may be one of the mechanism for treating asthma by ginkgo bioba extract.

PMID- 21189607
TI  - [Study of biological properties of cryopreserved stromal cells].
AB  - AIM: To observe the basical properties of adherent stromal cells in culture
      derived from cryopreserved bone marrow cells (BMCs), and to provide laboratory
      evidences for clinical application of cryopreserved stromal cells. METHODS: Fresh
      BMCs and adherent stromal cells cultured for 14 days in Dexter long-term culture
      system (fresh stromal cells) plus 5% DMSO-6% HES cryopreservatives were frozen in
      -80 degrees C refrigerator, and cryopreserved in - 196 degrees C liquid nitrogen
      for 2 weeks (the former is called cryopreserved BMCs, the latter called
      cryopreserved stromal cells). These cells were cultured in Dexter long-term
      culture system after they were thawed. We have examined the growth features,
      constituents and stimulating functions of the culture of these cells. RESULTS:
      Growth features: Cryopreserved BMCs produced adherent stromal cells, cell
      clusters and cell layer 1-2 days later than fresh BMCs. Cryopreserved stromal
      cells formed cell layer in 2nd day of culture, and were 12-18 h later than fresh
      stromal cells. Cryopreserved BMCs and stromal cells proliferated significantly
      less than fresh BMCs and stromal cells. Constituents: The ratio of fibrocytes and
      endothelial cells were lower, and the ratio of macrophages and fat cells were
      higher in culture of cryopreserved BMCs than that in fresh BMCs. The measurements
      in culture of cryopreserved stromal cells were much more significant compared
      with that in fresh stromal cells. Numbers of cells containing apoptic bodies in
      culture of cryopreserved BMCs and stromal cells were more than that in fresh BMCs
      and stromal cells. TBRR of cryopreserved BMCs and stromal cells were 92.5% and
      89.5% respectively. The expression rates of CD14 and HLA-DR in culture of
      cryopreserved BMCs and stromal cells were higher than that in fresh BMCs and
      stromal cells, and just in contrast with the expression rates of CD45 and CD33.
      Stimulating functions: CAFA and LTC-IC on the stromal cell layer derived from
      cryopreserved BMCs, cryopreserved stromal cells, fresh BMCs and fresh stromal
      cells were all growing well, and there were no significant differences among
      these groups. CONCLUSION: Biological properties of adherent stromal cells derived
      from BMCs and stromal cells were injured slightly and still maintained completely
      after cryopreservation with 5% DMSO-6% HES cryopreservatives.

PMID- 21189608
TI  - [Laser microdissection of a single cell from colon tissue for gene analysis].
AB  - AIM: To investigate the method of detecting gene expression in colon tissue at a
      single cell level. METHODS: Individual cell(s) were picked up from colon frozen
      section using laser microdissection. RNA was extracted, reverse transcribed to
      complementary DNA (cDNA). cDNA was then analyzed by nested reverse transcription
      polymerase chain reaction (nested RT-PCR) using two pairs of primers. RESULTS:
      Single cell(s) were selectively picked up using an ultraviolet laser
      micromanipulator. RNA was extracted, reverse transcribed and used for nested RT
      PCR. Amplification products of cDNA from down to a single cell could be clearly
      visualized in the agarose gel. CONCLUSION: The combined utilization of laser
      microdissection and nested RT-PCR provides an opportunity to analyze gene
      expression at single cell(s) level in colon tissue.

PMID- 21189609
TI  - [Experimental studies of genistein on the proliferation and apoptosis of human
      prolactinoma cells cultured in vitro].
AB  - AIM: To study the influence of genistein (GST) on the proliferation and apoptosis
      of cultured human prolactinoma cells. METHODS: MTT method and 3H-TdR
      incorporation and cell cycle analysis were used to examine the changes of
      proliferation and DNA synthesis of human prolactinoma cells under influence of
      GST and beta-estradiol (E2). Tdt-mediated dUTP nick end labeling (TUNEL) were
      employed to observe the effect of GST and E2 on the apoptosis of human
      prolactinoma cells. RESULTS: In a dose dependent manner, GST of different
      concentration could significantly inhibit the proliferation of human prolactinoma
      cells cultured in vitro. GST(10(-5) mol/L) could increase the proportion of cells
      in G1 phase from 55.3% up to 90.3%. E2 of different concentration could dose
      dependently increase the proliferation of human prolactinoma cells. E (10(-5)
      mol/L) could increase the proportion of cells in G2 phase from 15.6% up to 41.8%.
      However, a lower suppressive proliferation of cultured human prolactinoma cells
      was observed with GST and E2 together. GST, not E2, could significantly induce
      the apoptosis of human prolactinoma cells cultured in vitro. CONCLUSION: GST
      inhibits the proliferation, DNA synthesis and cell cycle of cultured human
      pituitary cells, and induces its apoptosis. E2 decreases partly the effect of GST
      on the suppression of proliferation, not apoptotic induction, of human
      prolactinoma cells cultured in vitro.

PMID- 21189610
TI  - [The study of inhibitory and apoptosis of K562 cells by antisense
      oligodeoxynucleotides].
AB  - AIM: To study the effect of bcr-abl fusion gene antisense phosphorothioate
      oligodeoxynucleotide (Aspo) on bcr-abl mRNA and apoptosis of K562 cells. METHODS:
      Cells were exposed to Aspo. P210 was measured by Flow Cytometry. Cellular bcr-abl
      mRNA was detected by RT-PCR mediquantitative analysis. Cell apoptosis was
      measured by Flow Cytometry and observed by electron microscope (EM). RESULTS: The
      P210 was down regulated or completely suppressed after 24h treatment with more
      than 5 micromol/L Aspo. The decrease of bcr-abl mRNA was about 45%. After
      incubation 48 h with 10 micromol/L Aspo. Also, 20% - 30% K562 cells were induced
      to apoptosis at 120 h when the cell number was 1 x 10(4)/ml at the beginning.
      While the cell number was 1 x 10(5)/ml, the apoptosis rate was 30% after 48 h
      culture and the typical morphology of apoptosis cell was observed under EM.
      CONCLUSION: bcr-abl Aspo could inhibit the expression of bcr-abl mRNA and P210.
      Also,it could induce apoptosis of K562 cells.

PMID- 21189611
TI  - [Effects of burn on synthesis and secretion of endothelin-1 in rat
      paraventricular nucleus of hypothalamus].
AB  - AIM AND METHODS: In order to investigate the pathophysiological role of ET-1 in
      paraventricular nucleus of hypothalamus (PVH) under burn, changes in synthesis
      and secretion of endothelin-1 (ET-1) in PVH after burn were observed by in situ
      hybridization and immunohistochemistry. The intensity of ET-1 mRNA and ET-1
      immunoreactivity (ET-1-ir) were quantized by image analysis. RESULTS: Compared
      with the control group (sham burn, 100% +/- 25%), no significant change in the
      intensity of ET-1 mRNA positive hybridization signal in PVH was found at 15 min
      postburn, while the intensity increased significantly both at 60 min (138% +/-
      26%, P < 0.05) and at 180 min postburn (167% +/- 18%, P < 0.01). Intensity of ET
      1-ir in the neurons in PVH decreased significantly at 15 min postburn to 6.3% +/-
      1.5% of the control (P < 0.01) and gradually recovered to 23.1% +/- 2.9% and to
      44.1% +/- 3.8% at 60 min and 180 min postburn respectively, while still
      significantly lower than that in control (P < 0.01). CONCLUSION: The results
      demonstrated that the synthesis and secretion of ET-1 in rat PVH increased
      significantly after burn in rats, suggesting that ET-1 in PVH played an important
      pathophysiological role under burn.

PMID- 21189612
TI  - [Changes of capillarity and blood flow of skeletal muscle in rat during
      acclimatization to hypoxia].
AB  - AIM: To study the changes of capillary density and blood flow of skeletal muscle
      in rat during acclimatization to hypoxia. METHODS: Myosin-ATPase histochemistry
      was used to assay the size and capillarity of skeletal muscle. Biomicrospheres
      method was used to determine blood flow in the rats at 5-, 15-or 30-day hypobaric
      hypoxic exposure (simulated 5 000 m altitude). RESULTS: It was found that cross
      sectional area of skeletal muscle fibers (including type I and type II) were
      decreased during acclimatization to hypoxia. Capillary density (CD) was increased
      in 15-day and 30-day groups but the capillary/fiber ratio (C/F) remained
      unchanged among all of the groups observed. There was no obvious difference in
      blood flow between hypoxic rats and control rats. CONCLUSION: Capillary
      neoformation does not occur in skeletal muscle of rat during acclimatization to
      hypobaric hypoxia. Increased capillary density due to atrophy of skeletal muscle
      fibre might benefit oxygen delivery at high altitude.

PMID- 21189613
TI  - [The elects of pH on the calcium homeostasis upon the kappa-opioid receptor
      stimulation in the myocytes].

PMID- 21189614
TI  - [The autonomic nervous system involved in regulation of immune function in rats
      during hypoxia].
AB  - AIM: To study of autonomic nervous system modulation of lymphocyte proliferation
      during hypoxia. METHODS: Rats were exposed to 5 km and 7 km altitude in a
      hypobaric chamber for 24 h or 48 h, the effect of autonomic nervous system on
      mitogen-induced spleen lymphocyte response to the acute hypoxia was investigated.
      RESULTS: When rats were exposed to 5 km altitude for 24 h, which inhibited spleen
      T lymphocyte proliferation induced by concanavalin (Con A), but the action was
      abolished through peripheral sympathetic-destroyed. When mouse were exposed
      anoxia environment at 0.07 MPa for 10 min, the norepinephrine and epinephrine in
      plasma were increased markedly. T cells of rats were in vitro incubated
      simultaneously with ACh showing a concentration dependent enhancement of T cell
      proliferation. The plasma levels of ACh were decreased after rats were exposed to
      5 km for 24 h. CONCLUSION: Autonomic nervous system was involved in the
      regulation of immune function in rats during hypoxia.

PMID- 21189615
TI  - [The effect of triptolide on the expression of BCL-2, ICE in pulmonary tissue of
      asthmatic guinea pig].

PMID- 21189616
TI  - [Effect of ICAM-1/LFA-1 on hypoxia/reoxygenation injury of cardiomyocytes
      mediated by neutrophils].
AB  - AIM: To observe the effect of hypoxia/reoxygenation on the adherence of
      neutrophils to cardiomyocytes and to investigate the effect of ICAM-1/LFA-1 on
      hypoxia/reoxygenation injury of cardiomyocytes mediated by neutrophils. METHODS:
      Count adhered neutrophils to cardiomyocytes suffering hypoxia,
      hypoxia/reoxygenation and normal culture, as well as adhered neutrophils that
      were blocked by anti ICAM-1 and LFA-1 monoclonal antibodies. Release of lactate
      dehydrogenase (LDH) was determined as injury index of cardiomyocytes. RESULTS:
      Adherence of with normal culture group (P < 0.01). The neutrophils to
      cardiomyocytes with hypoxia/reoxygenation were significantly increased compared
      lease of LDH by cardiomyocytes was also significantly increased (P < 0.01). There
      was no significant difference between hypoxia group and normal control (P >
      0.05). The adherence of neutrophils to hypoxia/reoxygenation cardiomyocytes was
      significantly inhibited by anti-ICAM-1 and anti-LFA-1 antibody compared with
      normal culture group (P < 0.01). While release of LDH markedly decreased (P <
      0.01). CONCLUSIONS: Hypoxia/reoxygenation increased the adherence of neutrophils
      to cardiomyocytes. ICAM-1 and LFA-1 mediated the enhanced adherence of
      neutrophils to hypoxia/reoxygenation cardiomyocytes. Anti-ICAM-1 and anti-LFA-1
      antibody attenuated the cytotoxic effects of neutrophils on hypoxia/reoxygenated
      cardiomyocytes. These results suggested that the damage of neutrophils on
      cardiomyocytes is partly mediated by ICAM-1/LFA-1. Anti ICAM-1 and LFA-1 antibody
      are both beneficial in protecting hypoxia/reoxygenation cardiomyocytes from
      injury mediated by neutrophils.

PMID- 21189617
TI  - [Study on the relationship of high hematocrit with changes of the blood viscosity
      during in the environment of altitude hypoxia].
AB  - AIM: To investigate the relationship of high hematocrit with changes of the blood
      viscosity during in the environment of altitude hypoxia. METHODS: Index of
      hemorheology was determined from populations with different time of inhabit
      highland and normal controls. RESULTS: (1) Hematocrit and RBC deformability were
      higher in all highland populations than that in normal controls, these increase
      were time-dependent. (2) The blood viscosity was increased significantly during
      the early stage of inhabit highland, and restored normal in late stage. (3) RBC
      aggregability was reduced significantly with time-dependent in highland
      populations. (4) The oxygen content of tissue was reduced significantly during
      the early stage of inhabit highland, and restored normal in late stage.
      CONCLUSIONS: In the environment of altitude hypoxia, RBC deformability increase
      and RBC aggregability decrease can suppress blood viscosity increase induced by
      erythrocytosis, these compensatory regulation is help to maintain the normal
      oxygen content of tissue.

PMID- 21189618
TI  - [Study on expression of ELAM-1 and ICAM-1 mRNA on microvascular endothelial cells
      during focal cerebral ischemia/reperfusion].
AB  - AIM: To evaluate the role of ELAM-1 and ICAM-1 in the course of inflammatory
      reactions during focal brain ischemia/reperfusion. METHODS: The focal brain
      ischemia/reperfusion model is carried by occluding middle cerebral artery. The
      expression of ELAM-1 and ICAM-1 mRNA after ischemia/reperfusion was evaluated
      with RT-PCR. RESULTS: No ELAM-1 and ICAM-1 mRNA were detected in the sham
      operated cortex and only little in the nonischemic cortex. The expression of ELAM
      1 and ICAM-1 mRNA were upregulated at 1 hour, peaked at 6 hour and 3 hour
      respectively and remained elevated for up to 48 hours after ischemia/reperfusion.
      CONCLUSION: ELAM-1 and ICAM-1 participate in brain injury during focal
      ischemia/reperfusion and both of them play an important role in leukocyte
      infiltration into the ischemic tissues.

PMID- 21189619
TI  - [Electro physiological characteristics of single potassium channel in isolated
      habenula neurons].

PMID- 21189620
TI  - [HOE642 (Cariporide) reduces the intracellular calcium overload of isolated
      immature rabbit ventricular myocytes induced by anoxia/reoxygenation].
AB  - AIM: To observe the effects of HOE642 (Cariporide) on intracellular free calcium
      in isolated immature rabbit ventricular myocytes induced by anoxia/reoxygenation,
      and to search the protective mechanism of the Na+/H+ exchange inhibitor on
      immature rabbit hearts. METHODS: The ventricular cardiomyocytes isolated from six
      New Zealand immature rabbit hearts were divided into three groups of each heart,
      which were attained by mean of collagenase (type II, 0.28 mg/ml) perfusion. All
      cells were incubated with calcium fluorescence indicator Fluo-3/AM, and then the
      intracellular free calcium was measured under the laser scanning confocal
      microscopy. As well as the creatine phosphokinase (CK) and lactic dehydrogenase
      (LDH) were measured. The baseline was measured after isolation without
      anoxia/reoxygenation. The control group received anoxic conditions for 60 minutes
      and reoxygenation for 30 minutes, then measured. The experiment group received
      the same conditions as control group with addition of HOE642 (1 micromol/L).
      RESULTS: After anoxia/reoxygenation, the intracellular free calcium of isolated
      immature rabbit ventricular myocytes and CK, LDH in control group increased
      significantly than baseline (P < 0.01), there were no significant difference of
      immature myocardial [Ca+]i and CK, LDH between experiment group and baseline (P >
      0.05), and the experiment group myocardial [Ca2+]i and CK, LDH reduced
      significantly than control (P < 0.01). CONCLUSION: HOE642 (Cariporide) may reduce
      intracellular calcium overload and the enzymes level (CK, LDH) in isolated
      immature rabbit ventricular myocytes induced by anoxia/reoxygenation, so the
      protective mechanism of HOE642 on immature rabbit heart may be by inhibition of
      the intracellular free calcium overload.

PMID- 21189621
TI  - [The changes of p62(dok) expression in the adipose cells of diabetic rat].

PMID- 21189622
TI  - [Effects of zinc on the free radical signals and apoptosis in liver with
      ischemia/ reperfusion injury].
AB  - AIM: In order to explore the preventive mechanism of zinc, the changes of free
      radical signals and apoptosis in hepatic ischemia/reperfusion injury (HIR) rats
      were observed. METHODS: The MDA levels in serum were measured by
      fluorophotometry, free radical signals in liver were analyzed with electron spin
      resonance (ESR) method; and apoptosis was assayed by flow cytometry (FCM).
      RESULTS: MDA levels in serum and free radical contents in liver were both
      increased in rats with HIR. After zinc supplementation, they were decreased.
      After HIR, the percentage of subdiploid cells was 57.72% while it was reduced to
      40.85% after zinc supplementation. CONCLUSION: Zinc may protect against HIR
      injury by inhibiting the production of free radicals in liver and hepatocellular
      apoptosis.

PMID- 21189624
TI  - [The experimental study on protective effects and its mechanisms of interleukin-1
      receptor antagonist on isolated swine kidney with ischemia/reperfusion].
AB  - AIM: To observe the protective effects and approach its mechanisms of interleukin
      1 receptor antagonist (IL-1ra) on the isolated swine kidney with
      ischemia/reperfusion (IR). METHODS: Thirty two swine were divided randomly into
      control group (n = 11), IR group (n = 11) and IL-1ra treatment group (IL-1ra
      group, n = 10) in the study. All swine were electrified. The kidneys were removed
      and put in ice-box immediately for detecting in control group. In IR group and IL
      1ra group, reperfusion pressure and flow rate were both observed once every 30
      minutes, the urine at the time of reperfusion 2 hours and the renal cortex at the
      time of reperfusion 2 hours and 30 minutes were taken for detecting. RESULTS: The
      resistance of perfusion in IL-1ra group was much lower than that in the IR group
      during reperfusion except start of reperfusion, there was a significant
      difference between IR group and IL-1ra group (P < 0.05, under the same). The
      content of MDA,TNF-alpha and IL-8 in the renal cortex in IR group were higher and
      the activities of SOD and Na(+) -K(+) -ATPase were lower than those in control
      group, In IL-1ra group, the content of MDA and the activity of SOD in renal
      cortex was respectively higher or lower than that in control group. Compared with
      IR group, the content of MDA and TNF-alpha and IL-8 in the renal tissues and
      urine protein were lower and the activities of SOD and Na(+) -K(+) -ATPase were
      higher in IL-1ra group. The serious degeneration and necrosis of renal tissue
      were observed in IR group under light microscope and electron microscope, but
      there was only slight degeneration in IL-1ra group. CONCLUSION: The results
      indicated that IL-1ra were effective in protecting the isolated swine kidney from
      IR injury.

PMID- 21189625
TI  - [The study of quantitative evaluation between age and dyspnea in the healthy].

PMID- 21189626
TI  - [Effect of inhibition by 17beta-estradiol on endothelin-induced proliferation of
      vascular smooth muscle cells].
AB  - AIM AND METHODS: To determine the effect of 17 beta-estradiol on proliferation of
      cultured vascular smooth muscle cells (VSMC) and expression of ET(A) receptor
      mRNA stimulated by endothelin-1 (ET-1). The experimental models of proliferation
      in cultured rat aortic smooth muscle cells induced by ET-1 was established. The
      3H-thymidine ([3H]-TdR) incorporation, cell counts and reverse transcription
      polymerase chain reaction (RT-PCR) were used in this study. RESULTS: BQ123, the
      selective ET(A) receptor antagonist, inhibited the increase of [3H]-TdR
      incorporation and cell number in response to ET-1 of VSMC.17 beta-estradiol may
      reverse the increase of [3H] TdR incorporation and cell number stimulated by ET
      1. 17 beta-estradiol downregulated of ET(A) receptor mRNA expression, with the
      maximum at 12 hours, which was partially prevented by tamoxifen, an estrogen
      receptor antagonist. CONCLUSION: The proliferation of VSMC stimulated by ET-1 was
      mainly through ET(A) receptor. 17 beta-estradiol inhibited the proliferation of
      VSMC stimulated by ET-1, which might be through downregulation of ET(A) receptor.

PMID- 21189627
TI  - [Changes of nitric oxide and endothelin-1 levels in rat brain tissue during
      cerebral vasospasm following subarachnoid hemorrhage and protective effect of
      nimodipine].
AB  - AIM: To investigate the changes of nitric oxide and endothelin-1 levels in brain
      tissue in rat with cerebral vasospasm (CVS) following subarachnoid hemorrhage
      (SAH), and the protective effect of nimodipine. METHODS: Wistar rats were divided
      randomly into SAH group, nimodipine-treated group and sham-operated group.
      Diameters of basilar artery before and after operation were measured, and dynamic
      changes of regional cerebral blood flow (rCBF), brain nitric oxide and endothelin
      1 levels were determined within 24 h. Pathological examination of hippocampus was
      also performed. RESULTS: SAH resulted in significant and persistent decrease of
      rCBF. Diameter of basilar artery was reduced markedly. Neurons in hippocampus CA1
      subfield were damaged severely. Both nitric oxide and endothelin-1 levels in
      brain tissue were increased significantly from 1 h to 24 h after SAH. However,
      the pathological changes of above parameters were not so severe in nimodipine
      treated rats. CONCLUSION: Increase of nitric oxide and endothelin-1 levels in
      brain tissue is probably involved in the development of ischemic brain damage
      caused by CVS after SAH. Nimodipine exerts its protective effect on brain neurons
      by antagonizing CVS and the pathological changes of nitric oxide and endothelin-1
      in brain tissue.

PMID- 21189628
TI  - [Effect of uncaria on evoked field potential of hippocampal slice in
      epileptogenic rat].
AB  - AIM: To investigate the effect of uncaria on evoked field potential of CA1
      hippocampal slice in epileptogenic model. METHODS: We made rats which were
      injected by pilocarpine as epileptic-models. The pathway of drug administration
      is titration adjacent to hippocampal slices. We recorded the evoked field
      potential of hippocampal slice by glass microelectrode extracellularly, and
      observed the effect of uncaria on the amplitude of population spike (PS) in CA1
      pyramidal cells in hippocampal slices. RESULTS: The uncaria with concentration of
      1 g/ml could reduce the amplitude of PS in CA1 of hippocampal slices. The average
      of fall was 27.64%, and restored in 8.71 minutes on average (n = 14, P < 0.01).
      CONCLUSION: Uncaria could reduce the amplitude of PS in CA1 of epileptic
      hippocampal slices remarkably. These results show that uncaria can inhabited the
      synaptic transfer activity of CNS remarkably, suggest that it has the distinct
      effect of anti-epilepsy.

PMID- 21189629
TI  - [The characteristic unit discharges related to epilepsy recorded synchronously
      from dual hippocampi induced by tetanization of the right dorsal hippocampus in
      rats].
AB  - AIM: To study the characteristics of unit discharges related to epilepsy of
      hippocampal neuron in both hemispheres in intact rats. METHODS: 44 pairs of cells
      were extracellularly recorded with dual glass microelectrodes from bilateral
      hippocampi before or after administration of repetitive tetani (0.4 - 0.6 mA, 2
      s, 60 Hz) to the right dorsal hippocampus. Repeated tetani were used about ten
      times at 5 or 10 min intervals to ensure full expression of afterdischarges
      without the tissue being in postictal refractory period. RESULTS: Primary or
      secondary unit afterdischarges of hippocampal neurons were evoked by tetani. They
      were characterized by bilateral asymmetry, moveability and interconversion
      between two hemispheres, which were observed in temporal lobe epileptic humans.
      In addition facilitatory or inhibitory, modulating or demodulating effect of
      tetani on spontaneous unit discharges depended on the basic firing rates or
      patterns of hippocampal cells before stimulation. Rhythmic cell bursting of the
      hippocampus was demodulated to tonic firing by Scopolamine (0.05 mg/kg, i.p.).
      Tetanus-induced inhibition of hippocampal unit discharges was observed after
      administration of scopolamine. CONCLUSION: Abnormal electrophysiological activity
      of bilateral hippocampi neurons evoked by tetanus may be the pathophysiological
      bases for dual hemispherical sclerosis and atrophy in temporal lobe epilepsy.

PMID- 21189630
TI  - [Effect of microinjection of L-arginine into the caudal pressor area of medulla
      oblongata on cardiovascular responses in rats].
AB  - AIM: To study the effect of microinjection L-arginine, a precursor for the
      synthesis of nitric oxide into the functionally identified caudal pressor area
      (CPA) in ventral surface of medulla oblongata. METHODS: Artery pressure (AP),
      renal perfusion pressure (RPP) and heart rate were recorded to study the effects
      of microinjection of NO related drugs into CPA. RESULTS: (1) Unilateral
      microinjection of L-arginine (60 - 100 nmol) into CPA produced prominent dose
      related depressor and bradycardic effects and reduced renal perfusion pressure.
      (2) Unilateral microinjection of L-arginine (100 nmol) 3 min after microinjection
      of methylene blue (10 nmol) into CPA did not significantly change AP and RPP. (3)
      Unilateral microinjection of L-glutamate (350 nmol) into CPA elicited pressor
      effect which was significantly dose-related attenuated by prior microinjection of
      L-arginine (60-100 nmol) into the same area. CONCLUSION: Theses results suggest
      that L-arginine-NO pathway in the CPA participates in the central regulation of
      arterial pressure and may have a key role in the inhibiting of glutamatergic
      neurotransmission in the anesthetized rats.

PMID- 21189631
TI  - [Studies on the mechanism of arterial in vitro calcification].
AB  - AIM: To investigate the stimulation to in vitro calcification of aorta by 25
      hydroxycholesterol or beta-glycerophosphate, and the relationship of the
      calcification with the secretion of osteocalcin and expression of type X collagen
      mRNA. METHODS: Aortic medial cells were obtained by explantation. Von Kossa
      staining was performed to show the in vitro calcification. Insoluble calcium of
      cellular layer was determined by biochemical method. And osteocalcin in the media
      was analyzed with radioimmunoassay. RT-PCR was used to determine the expression
      of type X collagen mRNA. RESULTS: Passaged cells showed negative von Kossa after
      28 days. While cells treated with 25-hydroxycholesterol or beta-glycerophosphate
      appeared many cell nodules with positive von Kossa staining, in witch much more
      insoluble calcium and supernatant osteocalcin were detected. Type X collagen mRNA
      was detected in cells treated with 25-hydroxycholesterol or beta-glycerophosphate
      but not in untreated cells. CONCLUSION: 25-hydroxycholesterol and beta
      glycerophosphate can accelerate the in vitro calcification of aortic media.
      Aortic medial cells secrete more osteocalcin and express type X collagen mRNA
      during calcification, which is similar to osteoblast, suggesting arterial
      calcification may share part of the same mechanism with the calcification of the
      bone.

PMID- 21189632
TI  - [Calcineurin signaling pathway is involved in cardiomyocyte hypertrophy mediated
      by calcium activators].
AB  - AIM: To investigate the effects of intracellular free calcium ([Ca2+]i) from
      different resources on calcineurin (CaN) dependent signaling pathway and
      cardiomyocyte hypertrophy. METHODS: Angiotensin II (Ang II,10(-7) mol/L),
      ryanodine (RY, 10(-7) mol/L), inositol (1,4,5)-trisphosphate (IP3, 10(-7) mol/L)
      were applied to stimulate the [Ca2+]i, CaN activity and protein expression were
      measured in primary cultured cardiomyocytes from Wistar rat. [Ca2+]i was measured
      using Fura-2/AM fluorescent technique. The incorporation of 3H-Leucine (3H-Leu)
      determined the synthesis rates of protein. RESULTS: Ang II, RY and IP3 increased
      [Ca2+]i, promoted CaN activity and protein expression, and 3H-Leu incorporation
      in cultured cardiomyocytes compared with control (P < 0.05 or P < 0.01).
      CONCLUSION: Cardiomyocyte hypertrophy is associated with the changes of cellular
      [Ca2+]i, but not with its resources. Indicating that CaN signaling pathway play
      an important role in the hypertrophy of cardiomyocytes.

PMID- 21189633
TI  - [Regulation of the transcription of oxidized low-density-lipoprotein receptor by
      angiotensin II].
AB  - AIM: To observe the effects of different concentrations Angiotensin II on the
      transcription of LOX1 in culture human umbilical vein endothelial cells and to
      explore its mechanism. METHODS: Reverse transcription-polymerase chain reaction
      (RT-PCR). RESULTS: (1) Angiotensin II cause a concentration-dependent increase of
      the level of LOX1 mRNA. (2) Losartan, the inhibitor of AT1 receptor subtypes,
      inhibited this effects. CONCLUSION: Angiotensin II stimulated the gene expression
      of LOX1 by activating AT1 receptor subtype in culture human endothelial cells.

PMID- 21189634
TI  - [Molecular cloning and three-dimensional structure modelling of HLA-DRalpha *
      0101, DRbeta1 * 04051 and DRbeta1 * 07011].
AB  - AIM: To study the correlation between the differences of three-dimensional
      structures among different HLA loci and their functions, and to investigate the
      potential usage of HLA conformational differences in predicting the occurrence of
      graft-versus-host disease (GVHD). METHODS: Total RNA were extracted from human
      peripheral blood, and reverse-transcription PCR (RT-PCR) were used to amplify the
      whole gene sequences of HLA-DR loci, and the PCR products were linked to vector
      and transformed to E.coli, and then sequencing. HLA-DR second exon amino acid
      sequences were inputted to computer, through internet to SWISS-MODELLING
      molecular modelling server to model their three-dimensional structure. RESULTS:
      The whole HLA-DR loci sequences were successfully reversibly transcript from 2
      normal unrelated donors. The sequencing results were completely identical to the
      published sequences of HLA-DRalpha * 0101, DRbeta1 * 04051 and DRbeta1 * 07011.
      The modelling results of the later two indicated that there were significant
      differences between their structures. CONCLUSION: The sequencing analysis of the
      whole HLA loci could clearly designate HLA allelic types, and three-dimensional
      structure modelling could directly identify the differences among them.
      Therefore, this study provide experimental foundation to the study of HLA
      structure and function, and uo the study of predicting GVHD after HLA
      incompletely matched hematopoietic stem cell transplantation (HSCT).

PMID- 21189635
TI  - [The influence of chemoreflex activities on heart rate variability].

PMID- 21189636
TI  - [Treatment effects of electroacupuncture on gentamycin ototoxicity and its
      mechanism in guinea pigs].
AB  - AIM: To investigate the effects of electroacupuncture on gentamycin (GE)
      ototoxicity in guinea pigs. METHODS: Brainstem auditory evoked potential (BAEP)
      and histochemistry were used in our study. RESULTS: Electroacupuncture reduced
      the elevated BAEP thresholds and shortened the prolongated BAEP wave latencies
      and interpeak latencies. It protected the activity of mitochondrial enzyme in the
      cochlear hair cells and cochlear stria vascularis. CONCLUSION: Electroacupuncture
      therapy can reduce GE ototoxicity. The mechanism of electroacupuncture therapy
      may be associated with its protected activity of mitochondrial enzyme and
      maintenance of energy metabolism of the cochlear hair cells and cochlear stria
      vascularis.

PMID- 21189637
TI  - [Effects of emodin on cytoplasmic adenine nucleotide content in guinea pig taenia
      coli cells].

PMID- 21189638
TI  - [The preliminary study of cross-hearing and its effects of checked ear in cat].
AB  - AIM: To study the cross-hearing and its mechanism of cat, so that preliminary
      explore the effects to checked ear on the amplitudes of ABR. METHODS: with the
      method utterly damaged the cochlea. We observed the cross-hearing and its effects
      on checked ear of the 16 normal cats. RESULTS: (1) The cross-hearing began to
      appear when the intensity of click > or = 75 dB( SPL), if the intensity of click
      was increased to 95 dB, the cross-hearing become the most obvious. (2) This cross
      hearing could be completely masked by 40 or 45 dB (SPL) steady white noise (SWN).
      (3) Make a comparison of two waves on the same time shaft indicates that the
      trough of cross-hearing wave and the crest of p(III), p(IV) wave by 95 dB click
      are corresponding. (4) To observe the alteration of amplitude of ABR evoked by 95
      dB click when load 40 dB SWN on the contralateral ear under the circumstance of
      the both ears are normal, we discovered that the 40 dB SWN can increase the
      amplitude of the wave p(III), p(IV) (P < 0.01). CONCLUSION: The experiment
      results demonstrate that the effect of cross-hearing to the amplitude of ABR on
      the checked ear depend on the corresponding situation of the wave crest and
      trough of both cross-hearing and ABR on the same time shaft. In fact, the ABR
      evoked by high intensity of click is a synthetic potential by cross-hearing and
      appeared on the stimulated ear.

PMID- 21189639
TI  - [The change of malondialdehyde and superoxide dismutase in apoptotic granulosa
      cell of rat PCO].
AB  - AIM AND METHODS: Rat PCO model was established according to the method of
      Bogovich. Granulosa cells were collected for apoptotic analysis by Tunel method
      and for measurement of MDA and SOD. RESULTS: (1) The percentage of apoptotic
      granulosa cells of rat PCO was higher than control group (P < 0.001). (2) Higher
      MDA and lower SOD were detected in granulosa cells of rat PCO. CONCLUSION: The
      change of MDA and SOD are associated with granulosa cell apoptosis in rat PCO.

PMID- 21189640
TI  - [Effects of several different irritation factors on leukocytes adhesion in
      microvessels].
AB  - AIM: The interrelation of adhesion between leukocyte and endothelium was studied
      by several irritation factors. METHODS: Leukocyte adhesion was observed by
      impulse electricity irritation, ischemia/reperfusion, endotoxin and IL-8 in
      venular of rat mesentery. RESULTS: The results showed these irritation factors
      resulted in a significant increase in the number of leukocytes adhesion along the
      venular endothelium of rat mesentery. IL-8 leaded to the most increase of
      leukocytes adhesion. Especially treated by IL-8 for 30 minutes. The number of
      leukocytes adhesion of the others was approximately identical. CONCLUSION: The
      study suggests that impulse electricity irritation, ischemia/reperfusion,
      endotoxin and IL-8 are able to induce leukocytes and endothelium adhesion, and IL
      8 of them has the most effect.

PMID- 21189641
TI  - [Effects of mixed cord blood serum on long-term culture of bone marrow
      hematopoietic cells].
AB  - AIM: To demonstrate the role of cord blood serum on dte long-term culture of bone
      marrow and provide the experimental foundation for its clinical use, the response
      of the bone marrow mononuclear cells to the mixed cord blood serum was
      investigated on the basis of Dexter culture system. METHODS: In ten samples of
      human bone marrow, 1 x 10(6) bone marrow mononuclear cells were planted onto the
      stromal cells layer and cultured for five weeks, Cobblestone area forming cells
      (CAFC), long-term colony-initiation cells (LTC-IC), and the nuclear cells count
      in the supernatant was observed. RESULTS: CAFC, LTC-IC were 37.1 +/- 12.4/(ml.
      well), 40.9 +/- 10.6/(ml. well) respectively in control group. The accounts were
      increased in the group of 10% MCBS, although it was less than that in mixed
      cytokines group. When combined with cytokines, 10% MCBS enhanced the growth of
      CAFC and LTC-IC obviously compared with that when cytokines were used alone. 20%
      MCBS failed to substitute the role of mixed cytokines plus fatal calf serum on
      the expansion of CAFC, LTC-IC and NCC. CONCLUSION: MCBS have the activity of
      stimulation for hematopoietic stem cells, which is analogous to SCF, IL-3, etc.
      Its nature and concentration remain to be investigated extensively.

PMID- 21189642
TI  - [Hippocampal slice - a model in vitro for screening antiepileptic drugs].
AB  - AIM: To establish a model in vitro for screening antiepileptic drugs. METHODS:
      Perfusing guinea pig hippocampal slice with penicillin offers a stable
      epileptiform discharge which was tested by two commonly clinically used
      antiepileptic drugs, phenytoin sodium and phenobarbital sodium at different
      concentration. RESULTS: The experimental result showed that penicillin induced
      epileptiform discharge in the hippocampal slice and two antiepileptic drugs,
      phenytoin sodium and phenobarbital sodium inhibition of this discharge induced by
      penicillin. CONCLUSION: This electrophysiological model has the advantage of
      simplicity, flexibility and ease of quantitation and has potential value for
      screen antiepileptic drugs and epilepsy research.

PMID- 21189643
TI  - [The labeling of procollagen gene probe by PCR and the detection of procollagen
      gene expression in hepatic stellate cells].
AB  - AIM: To establish a new method for labeling of procollagen gene probe and the
      detection of procollagen mRNA expression in HSC. METHODS: According to gene
      sequences from NCBI Gene Bank, the primers for the amplification of type I, III
      and IV procollagen genes were designed by OLIGO software, the procollagen genes
      were amplified by RT-PCR and were labeled by PCR and DIG-dUTP, and the probes
      were applied to detect procollagen mRNA expression in cultured hepatic stellate
      cells by in situ hybridization. RESULTS: The procollagen genes were successfully
      amplified by the Primers and RT-PCR and were labeled by DIG-dUTP and PCR, the
      procollagen mRNA expression in cultured hepatic stellate cells was detected by
      the probes. CONCLUSIONS: A new simplified method for labeling of procollagen
      genes is successfully found and it can be used for other gene amplification and
      labeling.

PMID- 21189644
TI  - [An automatic system controlled by microcontroller for carotid sinus perfusion].
AB  - AIM: To establish a new method for controlling automatically the carotid
      perfusion pressure. METHODS: A cheap practical automatic perfusion unit based on
      AT89C2051 micro controller was designed. The unit, LDB-M perfusion pump and the
      carotid sinus of an animal constituted an automatic perfusion system. RESULTS AND
      CONCLUSIONS: This system was able to provide ramp and stepwise updown perfusion
      pattern and has been used in the research of baroreflex. It can insure the
      precision and reproducibility of perfusion pressure curve, and improve the
      technical level in corresponding medical field.

PMID- 21189645
TI  - [The evaluation of the auditory function of tinnitus rats induced by salicylate
      acid and the treatment role on tinnitus by TCM herbs].

PMID- 21189646
TI  - [Antidiabetic agents: also new ways to give old agents].

PMID- 21189647
TI  - [New targets in type 2 diabetes therapy].
AB  - The growing number of patients with type 2 diabetes stimulates the development of
      new antidiabetic drugs. New targets are addressed, as SGLT2 in the kidney or
      enzymes of glucose metabolism in the liver which might help to lower glucose
      levels and to overcome insulin resistance. The forthcoming years will show which
      of the drugs in clinical trials will get marketing authorization.

PMID- 21189648
TI  - [New therapeutical approaches for treatment of irritable bowel syndrome].
AB  - Irritable bowel syndrome is a common functional disorder of the gut. The cause is
      not known. Symptoms can be quite variable and include abdominal pain, bloating,
      and sometimes bouts of diarrhea and/or constipation. It causes a great deal of
      discomfort and distress, but it does not permanently harm the intestine and does
      not lead to a serious disease, such as cancer. There are numerous treatment
      options in functional gastrointestinal disorders acting peripherally by
      influencing motility and visceral sensitivity. However, older 5-HT4 receptor
      agonists had limited clinical success because they were associated with changes
      in the cardiac function. New generation 5-HT4 receptor agonists, 5-HT,
      antagonists or partial antagonists are promising approaches to treat
      gastrointestinal dysmotility, particularly colonic diseases. A further new
      approach is the activation of chloride cannels within the gastrointestinal wall
      by the prostaglandin E metabolite lubiprostone. In patients with chronic
      constipation, lubiprostone produced a bowel movement, with sustained improvement
      in frequency as well as other constipation symptoms. Ongoing clinical trials
      suggest that linaclotide, a first-in-class, 14-amino acid peptide guanylate
      cyclase C (GC-C) receptor agonist and intestinal secretagogue is also an
      effective treatment for chronic constipation. The pharmacological profile
      suggests that orally administered linaclotide may be capable of improving the
      abdominal symptoms and bowel habits of patients suffering from of constipation
      predominant irritable bowel syndrome and chronic constipation. Data are emerging,
      but the efficacy and safety profile of these agents in the treatment irritable
      bowel disease appears encouraging. Further randomized controlled trials are
      warranted.

PMID- 21189649
TI  - [Potentially inappropriate medication for the elderly: adaptation and evaluation
      of a French consensus list].
AB  - BACKGROUND: Appropriate pharmacotherapy is one of the most important topics due
      to demographic development in many industrialised countries. The purpose of our
      work was to evaluate and adjust a French consensus list for Germany. MATERIALS
      AND METHODS: We conducted a thorough literature review with regard to the safety
      of drugs for the elderly. RESULTS: Originally, 34 criteria containing drugs or
      drug classes were classified as inappropriate. From these, we evaluated 12
      criteria as appropriate, and all others as potentially inappropriate, too.
      Frequently, drugs affecting the central nervous system, for example
      anticholinergics and benzodiazepines, were evaluated as potentially inappropriate
      medication. CONCLUSION: Our adapted list may be used as recommendation for
      appropriate drug prescribing in the elderly in Germany.

PMID- 21189650
TI  - [Drug therapy of cardiogenic shock. Improvement in hemodynamics is essential].

PMID- 21189651
TI  - [Interactions between St John's wort extract and finasteride?].

PMID- 21189652
TI  - [Immunological aspects of a case of extragenital endometriosis localized in the
      mouth].
AB  - To appreciate the role of the immune system in transportation and development of
      endometer cells in mouth, authors reported the results of immunological
      parameters analysis in one patient suffering to a mouth localisation healed
      endometriosis out of hormonal therapy in experimental and analytic study.
      Immunoglobulin A, G, M and C3, C4 complement fractions were measured by Mancini
      radial immunodiffusion. The count of CD4+, CD8+and B Cell was performed by BD
      FASCalibur flow cytometer. Autoimmune diseases were searched after by measuring
      autoantibodies using agglutination and immunofluoresence methods. The results
      showed any antibodies detected and the count of CD4, CD8 and B cells was normal.
      However, IgG and IgA increased. But C3, C4 factions and IgM decreased. This seems
      an immunological disorder which could be more explored in NK cells and cytokines
      study.

PMID- 21189653
TI  - My life as a mental health consumer.

PMID- 21189654
TI  - Modulation of amoebic hepatic abscess by the parasympathetic system.
AB  - The neuro-immune network, in which the vagus nerve is involved, provides feedback
      between its afferent branches for signalling central nervous system from sites of
      injury through cytokines and its efferent branches, which release acetylcholine,
      an anti-inflammatory neurotransmitter. For gain insight into the parasympathetic
      mechanisms participating in the inflammatory response in the liver, we studied
      the effects of a vagotomy on the innate immune response in hamsters with amoebic
      liver abscess. At 7 days post-infection, compared to the control, liver
      parasympathectomy resulted in a larger abscess size, a greater production of
      collagen fibres, fewer trophozoites, increased serum levels of IL-10 and IFN
      gamma and increased numbers of IL-10 and IFN-gamma-positive cells in situ, with
      no change in the number of macrophages and NK cells. Data indicate that the
      vagotomy disrupted the inflammatory response, causing an increase in the response
      against infection, then could favour the innervation of the liver by the
      sympathetic nervous system and would then take the control of the immune response
      by stimulating the conversion of macrophages to epithelioid cells; and through
      increased IL-10 production would induce the hepatic stellar cells to become
      myofibroblast collagen producer cells, thus forming a barrier of collagen and
      blocking trophozoite migration.

PMID- 21189655
TI  - Strain-specific immunity induced by immunization with pre-erythrocytic stages of
      Plasmodium chabaudi.
AB  - One of the most promising approaches in the efforts to produce a malaria vaccine
      involves the use of attenuated whole sporozoite immunizations. Attenuation may be
      achieved by the use of genetic modification, irradiation, chemical attenuation,
      or by the contemporaneous administration of antimalarial drugs that target only
      the erythrocytic stages of the parasite. Most research to date has focused on the
      efficacy of these approaches upon challenge with parasites homologous to those
      used for the initial immunizations. We, as have others, have previously shown
      that a component of the immunity achieved against the erythrocytic stages of the
      rodent malaria parasite Plasmodium chabaudi chabaudi is strain-specific, with a
      stronger immune response targeting the immunizing strain than genetically
      distinct strains. Here, we show that the immunity induced by infection with the
      pre-erythrocytic stages of these parasites, achieved via inoculation of
      sporozoites contemporaneously with mefloquine, also has a strain-specific
      component.

PMID- 21189656
TI  - [Spanish authors in the ideal library of G. Naude (1627): a European view of the
      Spanish culture and science at the beginning of the 17th century].
AB  - This article aims to analyze a European view of the 17th century Spanish culture.
      Naude's "Advis pour dresser une bibliotheque" (1627) - translated twice into
      English: "Instructions concerning erecting of a library" (1661) and "Advice on
      establishing a library" (1950) - represents a wide set of bibliographic
      recommendations that constitute, among many other things, an excellent
      observatory of the Spanish culture in such a delicate time.

PMID- 21189657
TI  - Abating progressive tissue injury and preserving function after CNS trauma: The
      role of inflammation modulatory therapies.
AB  - Brain and spinal cord injuries result in cognitive and/or sensorimotor
      impairments that can significantly diminish the quality of life for the patient
      and their carers, and result in healthcare system costs totaling in the billions.
      The current gold-standard of acute care for spinal cord injury is to administer
      high doses of glucocorticoids within 8 h of injury; administration after 8 h may
      be without effect or detrimental to the outcome of the patient. Therefore,
      improved pharmacological approaches for limiting the extent of tissue damage and
      neurological dysfunction in the acute injury setting are urgently needed. Early
      intervention in CNS injury by antagonizing or controlling the post-injury
      inflammatory process with pharmaceutical agents is a major focus of current
      clinical and preclinical investigations. In this editorial overview, recent
      clinical trials and preclinical studies of brain and spinal cord injuries are
      discussed, including studies focusing on the use of broad-spectrum
      immunosuppressive drugs (eg, minocycline); growth factors (eg, erythropoietin);
      dual anti-inflammatory and anti-vasospasm drugs, such as Rho and ROCK kinase
      inhibitors; and broad-spectrum anti-inflammatory drugs, such as PDE4 inhibitors.
      These new approaches hold great promise to improve outcomes for patients with
      brain and spinal injuries.

PMID- 21189658
TI  - Effects of lovastatin on the pharmacokinetics of diltiazem and its main
      metabolite, desacetyldiltiazem, in rats: possible role of cytochrome P450 3A4 and
      P-glycoprotein inhibition by lovastatin.
AB  - OBJECTIVES: The purpose of this study was to examine the effects of lovastatin on
      cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp) in vitro and then to
      determine the effects of lovastatin on the pharmacokinetics of diltiazem and its
      main metabolite, desacetyldiltiazem, in rats. METHODS: The pharmacokinetic
      parameters of diltiazem and desacetyldiltiazem were determined after orally
      administering diltiazem (12 mg/kg) to rats in the presence and absence of
      lovastatin (0.3 and 1.0 mg/kg). The effect of lovastatin on P-gp as well as
      CYP3A4 activity was also evaluated. KEY FINDINGS: Lovastatin inhibited CYP3A4
      enzyme activity with a 50% inhibition concentration of 6.06 uM. In addition,
      lovastatin significantly enhanced the cellular accumulation of rhodamine-123 in
      MCF-7/ADR cells overexpressing P-gp. Compared with the control (given diltiazem
      alone), the presence of lovastatin significantly altered the pharmacokinetic
      parameters of diltiazem. The areas under the plasma concentration-time curve
      (AUC) and the peak concentration of diltiazem were significantly increased (P <
      0.05, 1.0 mg/kg) in the presence of lovastatin. Consequently, the absolute
      bioavailability values of diltiazem in the presence of lovastatin (11.1% at 1.0
      mg/kg) were significantly higher (P < 0.05) than that of the control group
      (7.6%). The metabolite-parent AUC ratio in the presence of lovastatin (1.0 mg/kg)
      was significantly (P < 0.05) decreased compared with the control group.
      CONCLUSIONS: It might be considered that lovastatin resulted in reducing the
      first-pass metabolism in the intestine and/or in the liver via inhibition of
      CYP3A4 and increasing the absorption of diltiazem in the intestine via inhibition
      of P-gp by lovastatin.

PMID- 21189659
TI  - Exploring neurotherapeutic space: how many neurological drugs exist (or could
      exist)?
AB  - OBJECTIVES: Since high-throughput screening of compound libraries (virtual or
      real) against druggable targets is increasingly being used to discover therapies
      for brain disorders, it is crucial to ascertain if such screening methods
      adequately explore 'neurotherapeutic space (i.e. the total number of molecules
      that are or could be neuroactive)'. We present an approach to providing an
      estimate of the size of neurotherapeutic space. METHODS: Molecular modelling and
      statistical calculations were used to determine the number of molecules, which
      exist or could exist, with the necessary physicochemical and structural
      properties to be neurologically active drugs. KEY FINDINGS: Assuming eight
      fundamental types of drug-receptor interactions, five different functional groups
      per type of interaction and five different molecular platforms for each
      functional group array, we calculated the total number of molecules that could be
      contained within a 7 A radius sphere, used to define neuroactive chemical space.
      This calculation revealed that there are 6 * 10(15) molecules that could be
      neurological drugs. CONCLUSIONS: Clearly, when it comes to exploring
      neurochemical space, we are still in our infancy and conventional high-throughput
      screening provides only a very limited sampling of the neuroactive chemical space
      that is available to neurotherapeutic compounds.

PMID- 21189660
TI  - Bendamustine produces durable responses with an acceptable safety profile in
      patients with rituximab-refractory indolent non-Hodgkin lymphoma.
AB  - BACKGROUND: Although initially responsive to therapy, indolent non-Hodgkin
      lymphomas (NHLs) are generally incurable. Therefore, active and tolerable
      treatments for patients with relapsed or refractory disease are needed.
      Bendamustine, a mechlorethamine alkylator with novel mechanisms of action, is
      approved in the United States for rituximab-refractory indolent B-cell NHL.
      PATIENTS AND METHODS: Data from 2 North American multicenter studies with similar
      design, enrollment, and response criteria were pooled to evaluate safety and
      durability of response. Bendamustine was administered at 120 mg/m2 days 1 and 2
      every 21 days for 6-8 cycles. Endpoints included overall response rate (ORR),
      duration of response (DOR), progression-free survival (PFS), and safety. RESULTS:
      The studies enrolled 161 patients with a median of 2 previous chemotherapy
      regimens. Histologies included follicular (68%), small lymphocytic (20%),
      marginal zone (11%), and lymphoplasmacytic (1%) lymphoma. Sixty patients (34.1%)
      were refractory to their last chemotherapy, 53 (30.1%) were alkylating agent
      refractory. Overall response rate was 76% with 23% complete remissions (CRs) and
      unconfirmed CR (CRu). The median follow-up was 25.3 months (range, 24-27.8
      months) and DOR was 10 months (range, 8.3-14 months). At 1 and 2 years, 45% and
      23% of responders continued to respond. Among 127 patients previously treated
      with alkylators, ORR was 88% (28% CR/CRu) in responsive and 59% (12% CR/CRu) in
      refractory patients. Fifty opportunistic infections were reported in 48 patients.
      Second malignancies occurred in 9 patients (5.6%; 5 myelodysplastic syndromes, 2
      acute myelogenous leukemia, 1 chronic myelomonocytic leukemia, and 1 squamous
      cell carcinoma). CONCLUSION: Bendamustine induces durable responses with
      acceptable long-term safety in rituximab-refractory indolent NHL.

PMID- 21189661
TI  - [Academic resonances of the intellectual baggage brought by Augusto Pi Suner to
      Venezuela (1939-1962].
AB  - The article read over the intellectual connection between two physiologists, the
      Catalan exiled Augusto Pi Suner in 1939 and the Venezuelan Francisco De Venanzi
      beyond their common research subject like as: the academic insertion of the
      biological sciences and the related debate with the natural sciences; the
      scientific development and the necessity to attract the human resources for it;
      the publication of the project results by owner institutional reviews; the legal
      establishment at the highest govern level to development the scientific research.
      All of these subjects were developed when the scientific community in Venezuela
      are confirming her institutional organization.

PMID- 21189662
TI  - [Rape and transgression. Forensic medicine and sexual morality in Spain in the
      19th century].
AB  - The purpose of this paper is to analyse the importance of the contribution of the
      Spanish forensic medical discourse in the 19th century, and its application in
      cases of sexual harassment, to legitimize the sexual moral value of the time. For
      that reason we will analyse the main forensic medicine treaties edited in Spain
      during this century.

PMID- 21189663
TI  - [Hygiene and health preservation in the Luso-Brazilian medicine of the 18th
      century].
AB  - The present article analyzes the problematic of hygiene in the Luso-Brazilian
      medicine during the second half of 18th century. The chosen context to analysis
      is related to the changes of medical thought in Portugal along the period related
      to the appropriation of medical theories that circulated around the Enlightenment
      Europe. Besides, this paper approaches the ideas presented in medicine treatises
      of that time related to body care and health conservation, calling attention to
      the central role of hygiene along that period.

PMID- 21189664
TI  - [Physical anthropology and human "zoos": the exhibition of natives as a
      scientific popularization practice on the threshold of the 20th century].
AB  - All along the nineteenth century different anthropological exhibitions were held
      in many countries, in which people from a number of indigenous communities,
      especially transported from their homeland for the occasion, were exhibited
      publicly, both for citizenship's instruction and for specialists's "in vivo"
      studies on human biology. This paper presents a brief description of some of
      these scientific shows, and tries to relate them to contemporary human biology
      theories.

PMID- 21189665
TI  - [Social factors determining health (5). Chronic kidney diseases].

PMID- 21189666
TI  - [Health service research (3). Educational courses in health service research in
      the United States].

PMID- 21189667
TI  - [Revision of the laws concerning public health nursing, midwifery and nursing and
      on overview on public health nursing education. (8) Evaluation of public health
      nursing education].

PMID- 21189668
TI  - [Sociological factors determining health. (6) Metabolic syndrome and
      socioeconomic standing].

PMID- 21189669
TI  - [Health service research. (4) Basic knowledge of health service research].

PMID- 21189670
TI  - Neuropeptide systems as targets for parasite and pest control. Preface.

PMID- 21189671
TI  - Receptor-based discovery strategies for insecticides and parasiticides: a review.
AB  - Drug discovery is an iterative process with high risks and low chance of success.
      New genomics technologies allow veterinary medicine and agrochemical companies to
      validate and functionally screen new receptor-based targets, including
      neuropeptide G-protein coupled receptors, which were previously not amenable to
      high throughput screening. However this is just the first step in a long process
      to translate a mechanistic assay hit into a drug on the market. In addition to
      effectively eradicating pests on crops and parasites on their host, the molecules
      must also be safe, cheap to synthesise, formulatable and patentable. This is a
      costly process in which early attrition of unsuitable molecules is key to any
      successful program. Although first principle discovery is risky the ultimate
      benefits are considerable and future genomics resources will help to generate
      higher quality hits to strengthen the discovery pipeline.

PMID- 21189672
TI  - Nonpeptide ligands for peptidergic G protein-coupled receptors.
AB  - Neuropeptides play essential roles in many physiological systems in vertebrates
      and invertebrates. Peptides per se are difficult to use as therapeutic agents, as
      they are generally very unstable in biological fluid environments and cross
      biological membranes poorly. Recognition that nonpeptide ligands for peptide
      receptors have clinical utility came from the discovery that opiates (such as
      morphine) act by binding to G protein-coupled receptors (GPCRs) for which the
      endogenous ligands are a family of neuropeptides (enkephalins and endorphins).
      Basic research has revealed a very large number of distinct neuropeptides that
      influence virtually every aspect of mammalian physiology and considerable effort
      has been expended in the pursuit of new drugs that act through peptidergic
      signaling systems. Although useful drugs have been found to affect various
      aspects ofneuropeptide biology, most work has been devoted to the discovery of
      nonpeptide ligands that act as agonists or antagonists at peptidergic GPCRs.
      Similar opportunities are apparent for the discovery of nonpeptide ligands that
      act on invertebrate GPCRs. A consideration of the knowledge gained from the
      process as conducted for mammalian peptidergic systems can inform and illuminate
      promising strategies for the discovery of new drugs for the treatment and control
      of pests and parasites.

PMID- 21189673
TI  - Interaction of mimetic analogs of insect kinin neuropeptides with arthropod
      receptors.
AB  - Insect kinin neuropeptides share a common C-terminal pentapeptide sequence Phe1
      Xaa1(2)-Xaa2(3)-Trp4-Gly5-NH2 (Xaa1(2) = His, Asn, Phe, Ser or Tyr; Xaa2(3) =
      Pro, Ser or Ala) and have been isolated from a number of insects, including
      species of Dictyoptera, Orthoptera and Lepidoptera. They have been associated
      with the regulation of such diverse processes as hindgut contraction, diuresis
      and the release of digestive enzymes. In this chapter, the chemical,
      conformational and stereochemical aspects of the activity ofthe insect kinins
      with expressed receptors and/or biological assays are reviewed. With this
      information, biostable analogs are designed that protect peptidase-susceptible
      sites in the insect kinin sequence and demonstrate significant retention of
      activity on both receptor and biological assays. The identification of the most
      critical residue of the insect kinins for receptor interaction is used to select
      a scaffold for a recombinant library that leads to identification ofa nonpeptide
      mimetic analog. C-terminal aldehyde insect kinin analogs modify the activity of
      the insect kinins leading to inhibition of weight gain and mortality in corn
      earworm larvae and selective inhibition ofdiuresis in the housefly. Strategies
      for the modification of insect neuropeptide structures for the enhancement ofthe
      topical and oral bioavailability of insect neuropeptides and the promotion of
      time-release from the cuticle and/or foregut are reviewed. Promising mimetic
      analog leads for the development of selective agents capable of disrupting insect
      kinin regulated processes are identified that may provide interesting tools for
      arthropod endocrinologists and new pest insect management strategies in the
      future.

PMID- 21189674
TI  - Neuropeptides in helminths: occurrence and distribution.
AB  - Nematode neuropeptide systems comprise an exceptionally complex array of
      approximately 250 peptidic signaling molecules that operate within a structurally
      simple nervous system of approximately 300 neurons. A relatively complete picture
      of the neuropeptide complement is available for Caenorhabditis elegans, with 30
      flp, 38 ins and 43 nlp genes having been documented; accumulating evidence
      indicates similar complexity in parasitic nematodes from clades I, III, IV and V.
      In contrast, the picture for parasitic platyhelminths is less clear, with the
      limited peptide sequence data available providing concrete evidence for only
      FMRFamide-like peptide (FLP) and neuropeptide F (NPF) signaling systems, each of
      which only comprises one or two peptides. With the completion of the Schmidtea
      meditteranea and Schistosoma mansoni genome projects and expressed sequence tag
      datasets for other flatworm parasites becoming available, the time is ripe for a
      detailed reanalysis ofneuropeptide signalingin flatworms. Although the actual
      neuropeptides provide limited obvious value as targets for chemotherapeutic-based
      control strategies, they do highlight the signaling systems present in these
      helminths and provide tools for the discovery of more amenable targets such as
      neuropeptide receptors or neuropeptide processing enzymes. Also, they offer
      opportunities to evaluate the potential of their associated signaling pathways as
      targets through RNA interference (RNAi)-based, target validation strategies.
      Currently, within both helminth phyla, theflp signaling systems appear to merit
      further investigation as they are intrinsically linked with motor function, a
      proven target for successful anti-parasitics; it is clear that some nematode NLPs
      also play a role in motor function and could have similar appeal. At this time,
      it is unclear if flatworm NPF and nematode INS peptides operate in pathways that
      have utility for parasite control. Clearly, RNAi-based validation could be a
      starting point for scoring potential target pathways within neuropeptide
      signaling for parasiticide discovery programs. Also, recent successes in the
      application of in planta-based RNAi control strategies for plant parasitic
      nematodes reveal a strategy whereby neuropeptide encoding genes could become
      targets for parasite control. The possibility of developing these approaches for
      the control of animal and human parasites is intriguing, but will require
      significant advances in the delivery of RNAi-triggers.

PMID- 21189675
TI  - Neuropeptide physiology in helminths.
AB  - Parasitic worms come from two distinct, distant phyla, Nematoda (roundworms) and
      Platyhelminthes (flatworms). The nervous systems of worms from both phyla are
      replete with neuropeptides and there is ample physiological evidence that these
      neuropeptides control vital aspects of worm biology. In each phyla, the
      physiological evidence for critical roles for helminth neuropeptides is derived
      from both parasitic and free-living members. In the nematodes, the intestinal
      parasite Ascaris suum and the free-living Caenorhabditis elegans have yielded
      most of the data; in the platyhelminths, the most physiological data has come
      from the blood fluke Schistosoma mansoni. FMRFamide-like peptides (FLPs) have
      many varied effects (excitation, relaxation, or a combination) on somatic
      musculature, reproductive musculature, the pharynx and motor neurons in
      nematodes. Insulin-like peptides (INSs) play an essential role in nematode dauer
      formation and other developmental processes. There is also some evidence for a
      role in somatic muscle control for the somewhat heterogeneous grouping ofpeptides
      known as neuropeptide-like proteins (NLPs). In platyhelminths, as in nematodes,
      FLPs have a central role in somatic muscle function. Reports of FLP physiological
      action in platyhelminths are limited to a potent excitation of the somatic
      musculature. Platyhelminths are also abundantly endowed with neuropeptide Fs
      (NPFs), which appear absent from nematodes. There is not yet any data linking
      platyhelminth NPF to any particular physiological outcome, but this neuropeptide
      does potently and specifically inhibit cAMP accumulation in schistosomes. In
      nematodes and platyhelminths, there is an abundance of physiological evidence
      demonstrating that neuropeptides play critical roles in the biology of both free
      living and parasitic helminths. While it is certainly true that there remains a
      great deal to learn about the biology of neuropeptides in both phyla,
      physiological evidence presently available points to neuropeptidergic signaling
      as a very promising field from which to harvest future drug targets.

PMID- 21189676
TI  - Neuropeptide gene families in Caenorhabditis elegans.
AB  - Neuropeptides are short sequences ofamino acids that function in all
      multicellular organisms to communicate information between cells. The first
      sequence ofa neuropeptide was reported in 1970' and the number of identified
      neuropeptides remained relatively small until the 1990s when the DNA sequence of
      multiple genomes revealed treasure troves ofinformation. Byblasting away at the
      genome, gene families, the sizes ofwhich were previously unknown, could now be
      determined. This information has led to an exponential increase in the number of
      putative neuropeptides and their respective gene families. The molecular biology
      age greatly benefited the neuropeptide field in the nematode Caenorhabditis
      elegans. Its genome was among the first to be sequenced and this allowed us the
      opportunity to screen the genome for neuropeptide genes. Initially, the
      screeningwas slow, as the Genefinder and BLAST programs had difficulty
      identifying small genes and peptides. However, as the bioinformatics programs
      improved, the extent of the neuropeptide gene families in C. elegans gradually
      emerged.

PMID- 21189678
TI  - Neuropeptide signaling in insects.
AB  - Neuropeptides represent the largest single class of signal compounds and are
      involved in regulation of development, growth, reproduction, metabolism and
      behavior of insects. Over the last few years there has been a tremendous increase
      in our knowledge of neuropeptide signaling due to genome sequencing, peptidomics,
      gene micro arrays, receptor characterization and targeted gene interference
      combined with physiological and behavior analysis. In this chapter we review the
      current knowledge of structure and distribution of insect neuropeptides and their
      receptors, as well as their diverse functions. We also discuss peptide
      biosynthesis, processing and expression, as well as classification of insect
      neuropeptides. Special attention is paid to the role insect neuropeptides play as
      potential targets for pest management and as a basis for development of insect
      control agents employing the rational/structural design approaches.

PMID- 21189677
TI  - Control of nematode parasites with agents acting on neuro-musculature systems:
      lessons for neuropeptide ligand discovery.
AB  - There are a number of reasons why the development of novel anthelmintics is very
      necessary. In domestic animals, parasites cause serious loss of production and
      are a welfare concern. The control of these parasites requires changes in
      management practices to reduce the spread of infection and the use of therapeutic
      agents to treat affected animals. The development of vaccines against parasites
      is desirable but their development so far has been very limited. One notable
      exception is the vaccination of calves against infection by Dictyocaulus
      viviparous (lungworm) which has proved to be very effective. In domestic animals,
      the total market for anti-parasitic agents (both ecto- and endo-parasites) is in
      excess of a billion U.S. dollars. In humans there are serious problems
      ofmorbidity and mortality associated with parasite infections. 1.6 billion People
      throughout the world are infected with ascariasis (Fig. 1A) and/or hookworm.
      Approximately one-third of the world's population is suffering from the effects
      of intestinal nematode parasites, causing low growth-rates in infants, ill
      thrift, diarrhea and in 2% of cases, loss of life. Despite the huge number of
      affected individuals, the market for anti-parasitic drugs for humans is not big
      enough to foster the development of anthelmintics because most infestations that
      occur are in undeveloped countries that lack the ability to pay for the
      development of these drugs. The major economic motivator then, is for the
      development of animal anthelmintics. In both domestic animals and now in humans,
      there is now a level of resistance to the available anthelmintic compounds. The
      resistance is either: constitutive, where a given species of parasite has never
      been sensitive to the compound; or acquired, where the resistance has developed
      through Darwinian selection fostered by the continued exposure to the anti
      parasitic drugs. The continued use of all anthelmintics has and will, continue to
      increase the level of resistance. Cure rates are now often less than 100% and
      resistance of parasites to agents acting on the neuromuscular systems is present
      in a wide range of parasites of animals and humans hosts. In the face of this
      resistance the development of novel and effective agents is an urgent and
      imperative need. New drugs which act on the neuromuscular system have an
      advantage for medication for animals and humans because they have a rapid
      therapeutic effect within 3 hours of administration. The effects on the
      neuromuscular system include: spastic paralysis with drugs like levamisole and
      pyrantel; flaccid paralysis as with piperazine; or disruption of other vital
      muscular activity as with ivermectin. Figure 1 B and C, illustrates an example
      ofa spastic effect oflevamisole on infectious L3 larvae of Ostertagia
      ostertagiae, a parasite of pigs. The effect was produced within minutes of the in
      vitro application oflevamisole. In this chapter we comment on the properties of
      existing agents that have been used to control nematode parasites and that have
      an action on neuromuscular systems. We then draw attention to resistance that has
      developed to these compounds and comment on their toxicity and spectra of
      actions. We hope that some of the lessons that the use of these compounds has
      taught us may to be applied to any novel neuropeptide ligand that may be
      introduced. Our aim is then is to provide some warning signs for recognized but
      dangerous obstacles.

PMID- 21189679
TI  - Neuropeptide physiology in insects.
AB  - In a search for more environmentally benign alternatives to chemical pesticides,
      insect neuropeptides have been suggested as ideal candidates. Neuropeptides are
      neuromodulators and/or neurohormones that regulate most major physiological and
      behavioral processes in insects. The major neuropeptide structures have been
      identified through peptide purification in insects (peptidomics) and insect
      genome projects. Neuropeptide receptors have been identified and characterized in
      Drosophila and similar receptors are being targeted in other insects considered
      to be economically detrimental pests in agriculture and forestry. Defining
      neuropeptide action in different insect systems has been more challenging and as
      a consequence, identifying unique targets for potential pest control is also a
      challenge. In this chapter, neuropeptide biosynthesis as well as select
      physiological processes are examined with a view to pest control targets. The
      application of molecular techniques to transform insects with neuropeptide or
      neuropeptide receptor genes, or knockout genes to identify potential pest control
      targets, is a relatively new area that offers promise to insect control. Insect
      immune systems may also be manipulated through neuropeptides which may aid in
      compromising the insects ability to defend against foreign invasion.

PMID- 21189680
TI  - Neuropeptide biology in Drosophila.
AB  - Drosophila melanogaster is since decades the most important invertebrate model.
      With the publishing of the genome sequence, Drosophila also became a pioneer in
      (neuro)peptide research. Neuropeptides represent a major group of signaling
      molecules that outnumber all other types of neurotransmitters/modulators and
      hormones. By means of bioinformatics 119 (neuro)peptide precursor genes have been
      predicted from the Drosophila genome. Using the neuropeptidomics technology 46
      neuropeptides derived from 19 of these precursors could be biochemically
      characterized. At the cellular level, neuropeptides usually exert their action by
      binding to membrane receptors, many of which belong to the family of G-protein
      coupled receptors or GPCRs. Such receptors are the major target for many
      contemporary drugs. In this chapter, we will describe the identification,
      localization and functional characterization of neuropeptide-receptor pairs in
      Drosophila melanogaster.

PMID- 21189681
TI  - Neuropeptide receptors as possible targets for development of insect pest control
      agents.
AB  - Vaious insect species have a severe impact on human welfare and environment and
      thus force us to continuously develop novel agents for pest control.
      Neuropeptides constitute a very versatile class of bioactive messenger molecules
      that initiate and/or regulate a wide array of vital biological processes in
      insects by acting on their respective receptors in the plasmamembrane of target
      cells. These receptors belong to two distinct categories of signal transducing
      proteins, i.e., heptahelical or G protein-coupled receptors (7TM, GPCR) and
      single transmembrane containing receptors. An increasing amount ofevidence
      indicates that insect neuropeptide-receptor couples play crucial roles in
      processes as diverse as development, metabolism, ecdysis and reproduction. As
      such, they gain growing interest as promising candidate targets for the
      development of a new generation of species- and receptor-specific insect control
      agents that may generate fewer side effects. In this chapter, we will present
      some examples of insect neuropeptide receptors and aim to demonstrate their
      fundamental importance in insect biology.

PMID- 21189682
TI  - STAR trek: An introduction to STAR family proteins and review of quaking (QKI).
AB  - The STAR family has an extremely diverse role during development and in RNA
      metabolism. We have concentrated on QKI as an example of this pleiotropic
      activity and also presented some new data on the role of its conserved 3'UTRs
      gleaned from bioinformatics analysis of theoretical miRNA binding sites. We
      review the concept ofa direct pathway from signal transduction to activation of
      RNA, how this pathway could be the cell's quick response to developmental and
      physiological changes and how it must be tightly regulated.

PMID- 21189683
TI  - The star family member QKI and cell signaling.
AB  - The family of Signal Transduction and Activators of RNA (STAR) is named based on
      the intriguing potential for these proteins to connect cell signaling directly to
      the homeostasis of their mRNA ligands. Besides the commonly shared single RNA
      binding domain that displays heterogeneous nuclear ribonucleoprotein K homology
      (KH), STAR proteins also harbor domains predicted to bind critical components in
      signal transduction pathways, in particular the Src-family protein tyrosine
      kinases (Src-PTKs). Indeed, accumulating evidence in recent years has
      demonstrated that the RNA-binding activity and the homeostasis of downstream mRNA
      targets of STAR proteins can be regulated by phosphorylation in response to
      various extracellular signals. This chapter provides a short review of the STAR
      member QKI, focusing on the essential role of QKI in development of the central
      nervous system, possible mechanisms by which QKI may link cell signaling to the
      cellular behavior of its mRNA targets and how QKI dysregulation may contribute to
      human diseases.

PMID- 21189685
TI  - Post-translational regulation of star proteins and effects on their biological
      functions.
AB  - STAR (Signal Transduction and Activation of RNA) proteins owed their name to the
      presence in their structure ofa RNA-binding domain and several hallmarks of their
      involvement in signal transduction pathways. In many members of the family, the
      STAR RNA-binding domain (also named GSG, an acronym for GRP33/Sam68/ GLD-1) is
      flanked by regulatory regions containing proline-rich sequences, which serve as
      docking sites for proteins containing SH3 and WW domains and also a tyrosine-rich
      region at the C-terminus, which can mediateprotein-protein interactions with
      partners through SH2 domains. These regulatory regions contain consensus
      sequences for additional modifications, including serine/threonine
      phosphorylation, methylation, acetylation and sumoylation. Since their initial
      description, evidence has been gathered in different cell types and model
      organisms that STAR proteins can indeed integrate signals from external and
      internal cues with changes in transcription and processing of target RNAs. The
      most striking example of the high versatility of STAR proteins is provided by
      Sam68 (KHDRBS1), whose function, subcellular localization and affinity for RNA
      are strongly modulated by several signaling pathways through specific
      modifications. Moreover, the recent development of genetic knockout models has
      unveiled the physiological function of some STAR proteins, pointing to a crucial
      role of their post-translational modifications in the biological processes
      regulated by these RNA-binding proteins. This chapter offers an overview of the
      most updated literature on the regulation of STAR proteins by post-translational
      modifications and illustrates examples of how signal transduction pathways can
      modulate their activity and affect biological processes.

PMID- 21189684
TI  - Insights into the structural basis of RNA recognition by STAR domain proteins.
AB  - STAR proteins regulate diverse cellular processes and control numerous
      developmental events. They function at the post-transcriptional level by
      regulating the stability, sub-cellular distribution, alternative splicing, or
      translational efficiency of specific mRNA targets. Significant effort has been
      expended to define the determinants of RNA recognition by STAR proteins, in hopes
      of identifying new mRNA targets that contribute their role in cellular metabolism
      and development. This work has lead to the extensive biochemical characterization
      ofthe nucleotide sequence specificity of a handful of STAR proteins. In contrast,
      little structural information is available to analyze the molecular basis of
      sequence specific RNA recognition by this protein family. This chapter reviews
      the relevant literature on STAR domain protein structure and provides insights
      into how these proteins discriminate between different RNA sequences.

PMID- 21189686
TI  - Expression and functions of the star proteins Sam68 and T-STAR in mammalian
      spermatogenesis.
AB  - Spermatogenesis is one of the few major developmental pathways which are still
      ongoing in the adult. In this chapter we review the properties of Sam68 and T
      STAR, which are the STAR proteins functionally implicated in mammalian
      spermatogenesis. Sam68 is a ubiquitously expressed member of the STAR family, but
      has an essential role in spermatogenesis. Sam68 null mice are male infertile and
      at least in part this is due to a failure in important translational controls
      that operate during and after meiosis. The homologous T-STAR protein has a much
      more restricted anatomic expression pattern than Sam68, with highest levels seen
      in the testis and the developing brain. The focus of this chapter is the
      functional role of Sam68 and T-STAR proteins in male germ cell development. Since
      these proteins are known to have many cellular functions we extrapolate from
      other cell types and tissues to speculate on each of their likely functions
      within male germ cells, including control of alternative pre-mRNA splicing
      patterns in male germ cells.

PMID- 21189687
TI  - The role of quaking in mammalian embryonic development.
AB  - Functional studies of the mouse quaking gene (Qk) have focused on its role in the
      postnatal central nervous system during myelination. However, the death of the
      majority of homozygous mouse quaking alleles revealed that quaking has a critical
      role in embryonic development prior to the start of myelination. Surprisingly,
      the lethal alleles revealed that quaking has a function in embryonic blood vessel
      formation and remodeling. Further studies ofthe extraembryonic yolk sac showed
      that Qk regulates visceral endoderm differentiated function at the cellular
      level, including the local synthesis of retinoic acid (RA), which then exerts
      paracrine control of endothelial cells within adjacent mesoderm. Endoderm-derived
      RA regulates proliferation of endothelial cells and extracellular matrix (ECM)
      production, which in a reciprocal manner, modulates visceral endoderm survival
      and function. Although exogenous RA can rescue endothelial cell growth control
      and ECM production in mutants carrying a lethal mutation, which lack functional
      Qk, neither visceral endoderm function nor vascular remodeling is restored. Thus,
      Qk also regulates cell autonomous functions of visceral endoderm that are
      critical for vascular remodeling. Interestingly, quaking is highly expressed
      during normal cardiac development, particularly in the outflow tract, suggesting
      potentially unique functions in the developing heart. Together, the work on Qk in
      mammalian embryos reveals an essential, yet under appreciated, role in
      cardiovascular development. This suggests that certain functions may remain
      conserved in the early embryo throughout the evolution of nonvertebrate and
      vertebrate organisms and that additional roles for quaking remain to be
      discovered.

PMID- 21189688
TI  - Drosophila star proteins: what can be learned from flies?
AB  - Signal transduction and activation of RNA (STAR) family of RNA binding proteins
      are highly conserved through evolution indicating their core role during
      development, as well as in adult life. This chapter focuses on two Drosophila
      STAR proteins: held out wing (HOW), the ortholog of mammalian quaking (QKI) and
      Kep1, one of the four orthologs of mammalian Sam 68. I will emphasize the
      orthologs similarities in splicing pattern, functions and mode of actions of the
      two proteins relying on recent and earlier findings in the field. I will start
      with general description of the STAR proteins in Drosophila with an emphasis on
      their specific expression patterns.

PMID- 21189689
TI  - C. elegans star proteins, GLD-1 and ASD-2, regulate specific RNA targets to
      control development.
AB  - A comprehensive understanding of the C. elegans STAR proteins GLD-1 and ASD-2 is
      emerging from a combination of studies. Those employing genetic analysis reveal
      in vivo function, others involving biochemical approaches pursue the
      identification of mRNA targets through which these proteins act. Lastly,
      mechanistic studies provide the molecular pathway of target mRNA regulation.

PMID- 21189690
TI  - The branchpoint binding protein: in and out of the spliceosome cycle.
AB  - The Saccharomyces cerevisiae branchpoint binding protein (BBP) is a 53 kDa pre
      mRNA processing factor with characteristic STAR/GSG protein organization. This
      includes a central RNA binding site composed of an extended Type I KH domain with
      an adjacent QUA2 motif. Downstream of KH-QUA2 are two CCHC-type zinc knuckles and
      a proline-rich C-terminal interaction domain (Fig. 1A). The QUA1 homodimerization
      motif found upstream of the KH-QUA2 sequence in other STAR/GSG family members is
      absent in BBP and replaced by a site for the phylogenetically conserved binding
      partner, Mud2/U2AF65. BBP's name reflects the fact that it binds the conserved
      RNA sequence, UACUAAC, called the branchpoint motif found near the 3' end of
      yeast introns. This sequence contains the catalytic adenosine (underlined) which
      directs the first RNA transesterification reaction in splicing chemistry. BBP
      recruitment to the branchpoint initiates a series of spliceosomal subunit
      addition and rearrangement events that ultimately configures the active site
      ofthis enzyme. The mammalian homolog, ZFM1/ZNF162/D11S636/ SF1 (henceforth, SF1),
      was first identified in a screen for genes associated with Type 1 multiple
      endocrine neoplasia2 and was subsequently shown to act similarly to BBP in
      mammalian splicing. BBP/SF1 is essential for viability in organisms spanning the
      evolutionary spectrum from yeast to Caenorhabditis elegans to mice. In addition,
      mice heterozygous for a SF1 knockout allele show enhanced susceptibility to
      azoxymethane-induced colon tumorigenesis adding BBP/SF1 to the growing list of
      RNA processing factors implicated in genetic disease. Summarized below is our
      current understanding of BBP structure and its proposed multifaceted contribution
      to mRNA biogenesis and function. Reference to SF1 will be made to fill gaps in
      our understanding of BBP and to highlight areas of clear similarity or difference
      between yeast and mammals.

PMID- 21189692
TI  - Endothelial dysfunction and diabetes.

PMID- 21189691
TI  - Reaching for the stars: Linking RNA binding proteins to diseases.
AB  - The prototype STAR (Signal Transduction and Activation of RNA) protein is Sam68,
      the Src-associated substrate during mitosis of 68 kDa. Sam68, like all other STAR
      proteins, belongs to the large class of heteronuclear ribonucleoprotein particle
      K (hnRNP K) homology (KH) domain family of RNA-binding proteins. The KH domain is
      an evolutionarily conserved RNA binding domain that consists of 70-100 amino
      acids. The KH domain is one of the most prevalent RNA binding domains that
      directly contacts single-stranded RNA with a signature topology. Sam68 contains a
      single KH domain that harbors additional conserved N- and C-terminal sequences
      also required for RNA binding specificity and dimerization. Sam68 frequently
      contains post-translational modifications including serine/threonine, tyrosine
      phosphorylation, lysine acetylation, arginine methylation and sumoylation. The
      phosphorylation of Sam68 or its association with SH3 domain containing proteins
      has been shown to influence its RNA binding activity. Hence Sam68 behaves as a
      STAR protein, whereby extracellular signals influence its ability to regulate RNA
      metabolism. Studies in mice have revealed physiological roles linking Sam68 to
      osteoporosis, cancer, infertility and ataxia. The role of Sam68, a closely
      related family member quaking (QKI), the KH domain and their links with human
      disease will be discussed in the present chapter.

PMID- 21189693
TI  - Evaluation of endothelial function and effect of glycemic control (excellent vs.
      poor / fair control) on endothelial function in uncontrolled type 2 diabetes
      mellitus.
AB  - OBJECTIVE: To evaluate the endothelial functions before and after glycemic
      control in type II diabetes mellitus. MATERIAL AND METHODS: It was an open,
      randomized and comparative study on 30 patients of type 2 diabetes mellitus. The
      study was of 12 weeks spread over 5 visits. The initial visit (visit 1) is for
      screening of patients. Other visits (visits 2 to 5) constituted the follow up of
      patients. The primary efficacy parameters included blood sugar (fasting and
      postprandial) done on each visit and glycosylated hemoglobin (HbA1c) done at
      visits 1 and 5. Based on glycosylated hemoglobin (HbA1c) only poorly controlled
      and fairly controlled patients were included in the study. Brachial artery flow
      mediated vasodilatation (FMD) was studied in all these patient at visits 1 and 5
      to see the effect of glycemic control on endothelial functions. Results obtained
      were statistically analyzed with appropriate method. RESULTS: There was a
      significant improvement in endothelial functions in patients with fair, good and
      excellent control of diabetes. During uncontrolled state (HbA1c 10.08 +/- 0.48%)
      FMD was lowest, i.e., 2.88 +/- 0.53 at 1st week which improved to 11.94 +/- 3.33
      at 12th week with control of diabetes (HbA1c 6.74 +/- 0.16%). The FMD in patients
      who had fair control (HbAlc 8.45 +/- 0.30%) in the beginning was 6.74 +/- 2.43%
      and after excellent control in these patients FMD rises to 12.81 +/- 3.16%.
      CONCLUSION: Our data showed that the endothelial functions improved sequentially
      with control of diabetes from fair to good to excellent glycemic control.

PMID- 21189694
TI  - Coagulation profile in diabetes and its association with diabetic microvascular
      complications.
AB  - OBJECTIVES: To investigate the haemostatic parameters and to assesss their
      relationship with microvascular complications in type 2 diabetes mellitus.
      MATERIALS AND METHODS: Coagulation and fibrinolysis parameters were measured in
      60 type 2 diabetic patients (M:F 1:1) with (n=40) and without (n=20) diabetic
      microvascular complications and in 30 nondiabetic healthy subjects (M:F 1:1).
      RESULTS: The mean age of diabetic patients and healthy controls was 56.9 +/- 8.78
      and 53.2 +/- 7.58 respectively (p = 0.05). The plasma levels of PAI-1 (22.6 +/-
      6.85 vs 44.8 +/- 20.8, p = 0.00), serum fibrinogen (227.5 +/- 22.8 vs. 252.75 +/-
      40.23, p = 0.002) and vWF activity (99.4 +/- 28.18 vs. 144.78 +/- 36.21, p =
      0.00) were found to be increased in diabetics compared to healthy controls.
      Plasma PAI-1 levels (37.15 +/- 15.18 vs 48.65 +/- 22.29, p = 0.0) and vWF
      activity (123.19 +/- 29.63 vs. 155.57 +/- 34.61, p = 0.007) were significantly
      increased in diabetic patients with microvascular complications than those
      without microvascular complications.Amongst the diabetic patients, protein S
      activity (63.05 +/- 16.85 vs. 51.59 +/- 10.7, p = 0.002) was significantly lower
      in patients with microvascular complications than in patients without these
      complications. Diabetic retinopathy was associated with decreased protein S
      levels (63.05 +/- 16.85 vs. 48.48 +/- 8.72, p = 0.005) and vWF activity (123.19
      +/- 29.63 vs. 151.85 +/- 29.74, p = 0.009). Diabetic nephropathy was associated
      with increased PAI-1 levels (39.55 +/- 13.20 vs. 51.69 +/- 26.53, p = 0.02) and
      vWF activity (134.99 +/- 32.54 vs. 157.57 +/- 37.37, p = 0.007). Diabetic
      neuropathy did not show any significant relationship with any of the haemostatic
      variables. CONCLUSION: Hypercoagulable state as indicated by decreased
      fibrinolysis and increased coagulability is responsible as one of the factors for
      the development of microvascular complications of diabetes mellitus.

PMID- 21189695
TI  - Validity of quantitative unspun urine microscopy, dipstick test leucocyte
      esterase and nitrite tests in rapidly diagnosing urinary tract infections.
AB  - OBJECTIVES: Rapid diagnostic tests can screen out negative samples and can save
      valuable time and money. The study was conducted to assess the usefulness of
      leukocyte esterase, nitrate reductase and quantitative microscopic unspun urine
      wet mount examination in rapidly diagnosing urinary tract infections (UTI).
      METHODS: Four hundred and fifty samples were tested by semi-quantitative culture
      on cysteine lactose electrolyte deficient medium, microscopic examination of
      unspun urine for significant pyuria, dipstick leucocyte esterase test (LET) and
      nitrite test (NT). Culture was used as gold standard to evaluate the performance
      of direct microscopy and dipstick tests. RESULTS: Urine culture examination
      revealed significant bacteriuria (>10(5) cfu/ml) 98 (21.8%), in urine samples.
      Sensitivity, specificity, positive predictive value (PPV), negative predictive
      value (NPV) and the diagnostic odds ratio (DOR) of the dip-stick LET were 73.5%,
      58.5%, 33.0%, 88.8%, and 3.9 respectively; those of the dip-stick NT were 57.1%,
      78.7%, 42.7%, 86.8%, and 4.9 respectively; and those for microscopic significant
      pyuria detection were 68.4%, 60.8%, 32.7%, 87.3%, and 3.4 respectively. Highest
      sensitivity (95.9%), NPV (97.9%) and DOR (25.7) was obtained on combining
      microscopy and dip-stick LET and NT (either of them positive). This can
      potentially cut costs by 79%. CONCLUSION: Quantitative unspun urine wet mount
      microscopy and dipstick tests for leucocyte esterase and nitrite test should be
      added into routine laboratory practices for faster diagnosis of UTI.

PMID- 21189696
TI  - Probiotics--do they have a role in medicine and dentistry?
AB  - Probiotics are dietary supplements containing potentially beneficial bacteria or
      yeasts. They are administered in different quantities that allow for colon
      colonization. These products help in stimulating health promoting flora and also
      suppressing the pathologic colonization and disease spread. The use of probiotic
      plays an important aspect in dentistry too ever since the oral infections
      occupied the prime space among the other infections effecting the humans. This
      concept of microbial ecologic change both for medical and dental changes has
      accumulated a lot of evidence in recent times. But to date, no substantial
      literature and use has been postulated. There are claims that probiotics
      strengthen the immune system to combat allergies, stress, exposure to toxic
      substances and other diseases. There are reports of their beneficial use in HIV
      infection and cancers, mostly, the colo-rectal carcinomas. Their use in pre
      malignant and malignant oral disorders is yet to be probed. Strains of genera
      lactobacillus and bifidobacterium are the most widely used probiotic bacteria.
      This review is an attempt to discuss briefly the role of probiotics in medicine
      and dentistry.

PMID- 21189697
TI  - Patent ductus arteriosus with infective endarteritis.

PMID- 21189698
TI  - Hypoparathyroidism--a cause of reversible dilated cardiomyopathy.
AB  - Hypoparathyroidism is associated with chronic hypocalcaemia which can have a
      variety of manifestations including cardiovascular changes. We describe here a
      case of primary hypoparathyroidism associated with systolic dysfunction of left
      ventricle presenting as a dilated cardiomyopathy in addition to other
      manifestations.

PMID- 21189699
TI  - Retrosternal goitre with subclinical hyperthyroidism presenting with trochanteric
      fracture.
AB  - We report a 55-year-old female who presented with trochanteric fracture of right
      femur. Examination and investigation revealed a huge retrosternal goiter with
      compression of great vessels which was asymptomatic for more than two decades.
      Subsequent investigation confirmed it as a case of toxic multinodular goitre with
      subclinical hyperthyroidism which is the possible cause of secondary osteoporosis
      and fracture. Unusual presentation makes the case reportable.

PMID- 21189700
TI  - Subdural hematoma associated with immune thrombocytopenic purpura in two
      different clinical settings.
AB  - Subdural hematoma (SDH) is a rare complication of immune thrombocytopenic purpura
      (ITP) the incidence being around 2%. Although SDH usually occurs secondary to
      trauma, in bleeding disorders it may occur spontaneously. Here we report subdural
      hematoma in two uncommon settings, one patient with systemic sclerosis developing
      secondary ITP and consequently subdural hematoma and the other patient with
      chronic ITP developing subdural hematoma in the inter hemispheric region. In both
      the settings the patients recovered spontaneously without any surgical
      intervention.

PMID- 21189701
TI  - Primary hypoparathyroidism: psychosis in postpartum period.
AB  - We report a 30-yr-old lady who was being treated as postpartum psychosis. Patient
      had generalized tonic clonic convulsions and was found to have bilateral
      cataract. Her serum calcium, serum magnesium and serum parathyroid were low. On
      correction of serum magnesium her PTH did not increase. She was hence diagnosed
      as primary hypoparathyroidism. On correction of her serum calcium her psychosis
      improved.

PMID- 21189702
TI  - Pheochromocytoma presenting as hypertension in pregnancy.
AB  - Pheochromocytoma is a curable, rare cause of hypertension, characterized by
      symptoms and signs related to increased catecholamine secretion. Pregnancy and
      labour increase the risk of hypertensive crisis. However, antepartum diagnosis
      reduces both maternal and foetal mortality, allowing for safe cesarean section
      and resection of tumor. Control of hypertension with alpha blockers and beta
      blockers is the medical treatment. Surgical removal of the tumour is the
      definitive treatment. Hypertensive crisis needs to be treated aggressively. We
      report this case for the rare presentation of pheochromocytoma presenting as
      hypertension in pregnancy.

PMID- 21189703
TI  - An unusual case of Henoch-Schonlein purpura.
AB  - Vasculitis has protean manifestations with etiological non-specificity of
      histological lesions. The natural history of Henoch-Schonlein purpura in adults
      is less well established. We report an adult female patient who presented with
      palpable skin purpura and was evaluated to have IgA nephritis who remains stable
      on treatment with cyclophosphamide and steroids.

PMID- 21189704
TI  - Intractable seizures and metabolic bone disease secondary to celiac disease.
AB  - Celiac disease (CD) is Gluten sensitive enteropathy with a wide spectrum of
      severity and protean clinical manifestations. Patients with atypical (non
      diarrhoeal) presentations are missed as the diagnosis of Celiac Disease is not
      considered. We present three young girls (ages 18, 19, 23 at presentation) who
      were admitted to our hospital as intractable seizures. All had low serum calcium,
      features of rickets/osteomalacia and anaemia. This prompted us to consider
      malabsorption due to CD. The diagnosis of CD was confirmed by serologic tests
      (IgA transglutaminase and IgG antigliadin antibodies) and biopsy of the duodenum.
      In all patients gluten free diet not only provided drug free control of seizures
      but also helped correct other features of malabsorption like hypocalcaemia and
      anaemia as the primary pathology behind these symptoms was corrected. We wish to
      highlight that hypocalcaemia of CD which may present as intractable seizures can
      be treated only by treating CD with gluten free diet and not by oral vitamin D
      and Calcium alone.

PMID- 21189706
TI  - Diabetes: modern times.

PMID- 21189707
TI  - Ulcerative colitis presenting as toxic megacolon.

PMID- 21189705
TI  - Mixed connective tissue disorder and Castleman's disease.
AB  - We present a 16-year-old girl who presented with polyarthritis in association
      with Raynaud's phenomenon, malar rash, oral ulcers, photosensitivity and alopecia
      of 6 months duration. On evaluation, it emerged that she had a mixed connective
      tissue disorder with a mesangio-proliferative glomerulonephritis. Her Chest
      radiograph revealed a well defined left mid and lower zone opacity with evidence
      of a hilar mass on CT Thorax. Histopathological examination following CT guided
      biopsy of the mass revealed a hyaline vascular type of Castleman's disease. Mixed
      Connective Tissue Disorder with Castleman's Disease is a rare association; the
      patient presenting with varied and interesting manifestations. It is important to
      understand this association in view of management. The exact etio-pathogenesis of
      the autoimmune manifestations in patients with Castleman's disease is not clear.
      Treatment with immunosuppression can suppress both immune manifestations and
      result in tumour regression as well.

PMID- 21189708
TI  - Reporting a case of scrub typhus from Andhra Pradesh.

PMID- 21189709
TI  - Back on the chopping block.
AB  - Just as hospitals were trying to figure out how they'd adapt to the new
      healthcare reform law, the cochairmen of the federal deficit reduction commission
      delivered a proposal with a new raft of cuts targeting healthcare that some say
      would be devastating. "Let's study it and not dismantle the public infrastructure
      that is holding pieces together," says David Lopez, left, of Harris County
      Hospital District.

PMID- 21189710
TI  - A little slack. Existing doc-owned hospitals get break in new rule.

PMID- 21189711
TI  - Nominees sought for Hall of Fame. Deadlines for webcast, case study contest,
      Trustee of the Year on horizon.

PMID- 21189712
TI  - By the numbers. They don't miss a beat.

PMID- 21189713
TI  - Congenital combined deficiency of coagulation factors VII and II in a young
      adult.
AB  - We present herein a case of a young female with congenital combined coagulation
      factor VII (FVII) and factor II (FII) deficiencies. She was completely
      asymptomatic and found to have a prolonged prothrombin time during a routine
      preoperative evaluation. Low levels of plasma FVII and FII in the absence of an
      inhibitor confirmed the diagnosis in our patient. Congenital combined FVII and
      FIX deficiency as well as combined FVII and FX deficiency have been previously
      reported. The congenital combined deficiency of FVII and FII in our patient is
      exceptional and represents the first such instance in the English literature.
      Furthermore, we hypothesize that she had not shown any bleeding manifestations
      because of possible compensation for the missing factors II and VII by enhanced
      activity of some intrinsic coagulation pathway components or depression of
      fibrinolysis.

PMID- 21189714
TI  - Alpha-thalassemia genetic testing: an important anemia diagnostic tool in
      patients of African heritage.
AB  - Inherited alpha-thalassemia genotypes have been shown to have a rather high
      prevalence in some patient populations of African heritage. These genotypes lead
      to mild anemia with microcytic indices and a normal hemoglobin electrophoresis.
      In our outpatient department, we analyzed 54 consecutive patients of African
      descent with longstanding microcytic anemia, but no evidence of iron deficiency.
      We detected alpha-thalassemia gene deletions in 94 percent of these patients.
      Alpha-thalassemia genetic testing appears cost-effective in an otherwise
      unexplained, longstanding microcytic anemia in patients of African origin.

PMID- 21189715
TI  - Magenstrasse and Mill gastroplasty and sleeve gastrectomy as treatment for morbid
      obesity.
AB  - BACKGROUND: Laparoscopic nonbanded restrictive procedures are becoming more
      popular as staging and primary operations in bariatric surgery. The Magenstrasse
      and Mill (MM) procedure produces a restrictive gastric tubular pouch based along
      the lesser curvature; for the most part anatomy and physiology are preserved. In
      Sleeve Gastrectomy (SG), 80% of normal stomach is resected to produce restriction
      and to decrease ghrelin levels. METHODS: This is a retrospective nonrandomized
      study evaluating the medical records of patients who had the laparoscopic MM
      (LMM) and laparoscopic SG (LSG) between January 2007 and October 2008. One
      bariatric surgeon performed the LMM and two bariatric surgeons performed the LSG.
      RESULTS: A total of 20 patients were identified: 13 SG and 7 MM. The mean age was
      50 for the MM vs 42.9 for the SG. For the MM, the mean preoperative body mass
      index (BMI) was 65.4 +/- 11.1 kg/m2, with a mean excess weight of 282 +/- 73.7
      kg. For the SG, the mean preoperative body mass index was 47.5 +/- 8.3 kg/m2,
      with a mean excess weight of 156.1 +/- 52.6 kg. The mean excess weight loss after
      six and 12 months for the M&M was 35 +/- 10.5% and 20.1 +/- 1.4%, vs 52.4 +/-
      17.8% and 49% +/- 15.4% for the SG. Follow-up of one year was achieved in two M&M
      patients and three SG patients. Median follow-up of all patients was seven months
      (range 12-1). CONCLUSION: This is a short-term retrospective outcome study. The
      LMM patients were larger than LSG patients. Total weight loss was greater for the
      LMM patients. Operative time for the LMM is shorter. The percent excess weight
      loss in the short-term 12 month period was more in the LSG compared to the LMM.
      Long-term follow-up is needed.

PMID- 21189716
TI  - Bivalirudin: a review of pharmacology and therapeutic use.

PMID- 21189717
TI  - Adoption of the medical home in Connecticut.
AB  - OBJECTIVE: To examine the implementation of key features of the medical home
      concept, with its emphasis on chronic care and disease management, care
      coordination, case management and timely access to care in Connecticut primary
      care practices, and to examine predictors of its implementation in Connecticut.
      METHODS: Primary care physicians affiliated with the Connecticut Chapter of the
      American College of Physicians (n = 1088), the Connecticut Chapter of the
      American Academy of Pediatrics (n = 699), and the Connecticut Academy of Family
      Physicians (n = 376) were invited to participate in a brief online survey.
      Participation was limited to physicians who were actively engaged in primary-care
      medicine as determined by the respondent based on information provided as part of
      the survey. RESULTS: Four hundred ninty-eight primary-care physicians practicing
      in Connecticut completed the survey resulting in an overall response rate of 23%.
      In general, many of the core components of the medical home concept were not
      widely implemented yet in Connecticut. Most common were registries of patients
      with chronic diseases (33% of sample) and open or advanced access scheduling (57%
      of sample). Electronic medical records (EMR) systems were currently used by 39%
      of primary care physicians. Substantial differences by specialty were observed,
      with chronic disease registries and advanced/open access scheduling significantly
      less common among internists, and EMR systems significantly less common among
      pediatricians. The only factor consistently associated with increased likelihood
      of implementing the medical home concept was larger practice size (number of
      practicing physicians within the medical practice). Open or advanced access
      scheduling resulted in significantly shorter appointment wait times for patients.
      CONCLUSION: These results reveal that the adoption of the medical home model
      among Connecticut primary-care physicians remains in its infancy and suggests
      possible approaches to removing barriers to the implementation of the medical
      home model in Connecticut.

PMID- 21189718
TI  - The new health-care system: results of a round table discussion.

PMID- 21189719
TI  - Creating a medical home through the 340B Drug Pricing Program.
AB  - OBJECTIVE: This study was designed to track inpatient and outpatient utilization
      before and after the implementation of the 340B Drug Pricing Program in a public
      university hospital. METHODS: Before and after design built upon administrative
      clinical and financial data. RESULTS: Outpatient and emergency department
      utilization rates increased with small increments of direct cost. Inpatient
      utilization decreased while inpatient length of stay increased with over three
      million dollars in direct cost savings. CONCLUSIONS: Improving continuity of care
      for patients without a usual source of care may have the effect of creating a
      "medical home." The 340B Drug Pricing Program may be one policy tool to improve
      care for the underserved while increasing outpatient utilization and decreasing
      inpatient utilization and costs.

PMID- 21189720
TI  - "Hi doctor, I'm over here".

PMID- 21189721
TI  - Connecticut and its cerebral palsied children. 1960.

PMID- 21189722
TI  - "Meaningful use".

PMID- 21189723
TI  - Constructive "fine tuning"--one hundred years later.

PMID- 21189724
TI  - A year in the life of CSMS.

PMID- 21189725
TI  - CSMS: standing up for you.

PMID- 21189726
TI  - Doctors' comments on the Connecticut State Medical Survey.

PMID- 21189727
TI  - The PECOS online Medicare enrollment application.

PMID- 21189728
TI  - Preparing Europe for a new renaissance: how science can help restore sustainable
      prosperity.
AB  - On 6 October 2009, ERAB (European Research Area Board) presented its first annual
      report "Preparing Europe for a New Renaissance--A Strategic View of the European
      Research Area". As a vision paper it paints a picture, in broad strokes, of where
      the European Research Area (ERA) needs to go by 2030--for the sake of the
      European Union, and of the world at large. For this purpose, the ERAB Conference
      entitled "Preparing Europe for a new Renaissance" was held on May 6-7, 2010, in
      Seville, Spain. The aim of the ERAB Conference was to discuss widely with public
      and private stakeholders the implementation of the Strategic view on European
      Research Area. The Commissioner Maire Geoghegan-Quinn deserves a special mention
      since set a challenge to the ERAB Conference in her speech. Thus, she asked the
      conference to provide her with ten concrete proposals on how research, innovation
      and science can contribute to addressing society's grand challenges, to prepare
      Europe's post-crisis smart, green economy and society. The ERAB welcomed the
      challenge. Based on the feedback from the conference delegates and own
      discussions the ERAB came up with 10 key recommendations. Below we reproduce a
      speech by the European Commissioner for Research, Innovation and Science, Maire
      Geoghegan-Quinn given at the ERAB Conference.

PMID- 21189729
TI  - Research on human cells reprogramming in Andalusia (Spain): Quo vadis Europe?
AB  - Andalusia has a special situation within Spain, among the group of countries that
      lead biomedical research on embryonic cell reprogramming at a global level,
      research which seems to have overcome the moral and ethical controversy
      surrounding other research techniques involving the creation-destruction of human
      embryos. Nevertheless, as there is no common European conception of human life,
      some ethical problems could emerge in the near future when it comes to patenting
      the results of these cell-reprogramming techniques at a European level.

PMID- 21189730
TI  - The new law on gene diagnostics in Germany--an overview about the main
      principles.
AB  - On the 1st of February, 2010--more than 20 years after the first considerations
      and after several drafts of laws have been submitted to the German Lower House of
      Parliament, the law on gene diagnostics dated on 31.7.2009, get in to force. The
      law rules on genetic testing for purposes of health, parentage and descent in
      case of the law concerning refugees and foreigners, insurance and employment. It
      creates no independent basis for authorizing the performance of genetic tests. It
      regulates the application in which they are forbidden and mandatory conditions
      which must be followed in the conduct of lawful genetic investigations. Like many
      German laws in the field of biomedicine, it has gaps and rating contradictions.
      It is based on the political minimum consensus and not on the current state of
      medical research. For this reason, there are gaps rules, where political
      consensus was not possible, such as rules on genetic investigation for research
      (biobank) or PID. In any case the GenDG brings more security in the field of
      genetic diagnostics. In interaction with the general provisions the GenDG
      regulates genetic investigation to a sufficient extent.

PMID- 21189731
TI  - Synthetic biology & human health: some initial thoughts on the ethical questions
      and how we ought to approach them.
AB  - The emerging field of synthetic biology aims to move beyond our current state of
      being able to read and manipulate genetic code to being able to write it. Drawing
      on the other disciplines such as engineering it will allow scientists to create
      new artificial biological systems as well as modify and redesign systems which
      already exist in nature. This is likely to result in a range of new and
      innovative applications. This essay has three aims. First, it provides a brief
      introduction to synthetic biology, explains what it is, some of the ways in which
      it has been defined and some of its possible future applications. Second, the
      essay considers some of the ethical questions which synthetic biology may raise.
      Finally, the essay reflects on how we ought to answer these sorts of questions
      and suggests a more reflective, philosophical approach.

PMID- 21189732
TI  - HR policy. Positive change.

PMID- 21189733
TI  - Human resources. Wake up to your true potential.

PMID- 21189735
TI  - Self care. You have the power.

PMID- 21189734
TI  - Primary care. A change of practice.

PMID- 21189736
TI  - A word can be worth a thousand pictures.

PMID- 21189737
TI  - Accountability: a tale of two future nurses.

PMID- 21189738
TI  - Nurses' response time to call lights and fall occurrences.
AB  - Nurses respond to fallers' call lights more quickly than they do to lights
      initiated by non-fallers. The nurses' responsiveness to call lights could be a
      compensatory mechanism in responding to the fall prevalence on the unit.

PMID- 21189739
TI  - Better evaluation tools needed.

PMID- 21189740
TI  - Implementing staff nurse geriatric education in the acute hospital setting.
AB  - The implementation and evaluation of staff nurse geriatric educational
      interventions on medical units in an urban teaching hospital are described.

PMID- 21189741
TI  - Women and cardiovascular disease: an evidentiary review.
AB  - Coronary artery disease (CAD) kills more women than all cancers combined, yet
      their diagnosis can be missed or delayed. Detection of CAD at an earlier stage in
      women may result in earlier recognition and treatment and subsequently lower
      associated morbidity and mortality rates. The purpose of this evidentiary review
      is to examine the effect of gender on the recognition, treatment, and outcomes of
      coronary artery disease in women.

PMID- 21189742
TI  - Location of blood pressure measurement.
AB  - Health care workers in a rural community hospital were queried about factors
      associated with blood pressure (BP) accuracy. Results suggest remedial education
      regarding cuff size, patient position, arm position, and location for accurate BP
      measurement is needed.

PMID- 21189743
TI  - Impacting health through on-the-job counseling: role for professional nurses.
AB  - Employers have implemented a variety of workplace health promotion programs. An
      initiative in which experienced professional nurses were contracted to provide
      counseling sessions to employees at the workplace is described.

PMID- 21189744
TI  - A matter of life and death: the implementation of a Mock Code Blue Program in
      acute care.

PMID- 21189745
TI  - Multiple sclerosis.

PMID- 21189746
TI  - Journal clubs on the night shift: a staff nurse initiative.

PMID- 21189747
TI  - Are we moving forward on new clinical performance measures?

PMID- 21189748
TI  - A look at whether Medicare will consider cost effectiveness when setting
      reimbursement rates.

PMID- 21189749
TI  - A 'quiet revolution' in nephrology.

PMID- 21189750
TI  - Dissecting the bundle: the final rules for the prospective payment system for
      pediatric dialysis.

PMID- 21189751
TI  - DOPPS practice monitor to help evaluate impact of bundle on hemodialysis patient
      care.

PMID- 21189752
TI  - Transplant Games after 20: still helping donors, recipients celebrate the gift of
      life.

PMID- 21189753
TI  - Fistula First clarifies definition of preferred access.

PMID- 21189754
TI  - EHRs: what's all the fuss about?

PMID- 21189755
TI  - What can EHRs do for the quality of care you deliver?

PMID- 21189756
TI  - RPA revises guidelines on the use of dialysis.

PMID- 21189757
TI  - Caries experience in asthmatic children: a review of literature.
AB  - AIM: This review explores the discriminating factors involved for increased
      caries experience in asthmatic children. BACKGROUND: Dental caries is the single
      most common chronic disease of childhood. Children with chronic medical
      conditions are considered high caries risk. Asthma is one of the most common
      chronic medical conditions in childhood. MATERIAL: 27 studies examined the asthma
      caries causative relationship. Most of them were cross sectional studies; only 5
      longitudinal studies were reported. In the literature, there is a lack of
      consensus regarding the relationship between dental caries and asthma in a child
      population. CONCLUSION: Despite the fact that some relatively recent studies have
      provided little evidence for an asthma-caries causative relationship, the
      majority and the most recent reports have concluded that the individualistic
      nature of asthmatic condition, through either its disease status or its
      pharmacotherapy (diferent combinations of medicaments), or attempts to alleviate
      the condition's physiologic sequelea, carries several factors for an increased
      caries risk.

PMID- 21189758
TI  - Teething: myths and facts.
AB  - From grandmothers to medical professionals, everyone seems to have a list of
      symptoms they believe are linked to teething. During this time period of an
      infant's life, passive immunity due to maternal antibodies wanes and exposure to
      a wide variety of childhood illnesses occurs. Parental false beliefs associated
      with teething may interfere with the prompt diagnosis and management of a range
      of serious illnesses. Strong parental beliefs which are not borne out by evidence
      will unlikely change until professionals (most of whom are also parents) change
      theirs. Therefore, there is a need to know the facts and the false beliefs
      attributed to teething. Medical professionals need to be educated about teething
      to provide reasonable explanations to concerned caregivers. This article examines
      the signs and symptoms frequently attributed to teething and their possible
      alternative causes. The contemporary principles of the management of teething are
      discussed, including supportive care.

PMID- 21189759
TI  - Sleep disordered breathing in children--a review and the role of a pediatric
      dentist.
AB  - Among the many factors important in children's development is sleep. Sleep
      disorders can impair children's sleep and lead to negative consequences. The most
      common sleep disordered breathing (SDB) in children is obstructive sleep apnea
      (OSA). One of the main causes of childhood SDB is enlargement of the tonsil
      tissues and, in most cases, their removal serves as an ultimate treatment of SDB.
      However, it remains unclear what proportion of children with enlarged tonsil
      tissue suffer from SDB. Dentists are becoming increasingly aware of the issue of
      SDB as they are sometimes involved in treatment of this condition using oral
      appliances. Moreover, as dentists often look into children's mouths, they can
      play an active role in identifying those with enlarged tonsils and referring them
      for sleep assessment. This review focuses on the diagnosis and treatment of SDB
      and also on the utility of oral appliances in the management of this disorder.

PMID- 21189760
TI  - Comparative evaluation of bactericidal potential of four root canal filling
      materials against microflora of infected non-vital primary teeth.
AB  - BACKGROUND AND OBJECTIVES: Since complete debridement of the root canals of the
      primary teeth is not practically possible due to the highly variable root canal
      anatomy, success of the endodontic therapy depends partly on the use
      ofantibacterial irrigating agents and root canal filling materials. Recent
      literature indicates that anaerobes comprise a majority of the bacteria in
      necrotic root canals ofprimary teeth. The study determined the antibacterial
      effectiveness of four root canal filling materials namely Calcium hydroxide, Zinc
      oxide eugenol, Vitapex and Metapex against microbial specimens obtained directly
      from necrotic root canals of primary teeth. METHOD: Microbial specimens were
      collected using sterile paper points, from 15 primary maxillary and mandibular
      posterior teeth of randomly selected children in the age group of 4-10 years with
      infected non vital primary teeth, requiring pulpectomy procedure. The microbial
      specimens collected were subjected to microbiological analysis and the
      antimicrobial potential of root canal filling materials were tested using Agar
      diffusion technique. RESULTS: were statistically analyzed using one-way ANOVA.
      Facultative/Aerobic organisms were isolated in all the cases, anaerobic organisms
      were isolated in 80% of the cases, and Candida albicans was isolated in 1 case.
      ZOE showed superior inhibitory activity against most of the organisms isolated
      followed by Vitapex, Calcium hydroxide and Metapex in descending order.
      CONCLUSION: Our data may be useful as a guide for relative antimicrobial
      effectiveness or non-effectiveness of the materials employed. In vivo studies are
      required to state the specific antimicrobial activity and merits and demerits of
      any of the test filling material.

PMID- 21189761
TI  - Antimicrobial effectiveness of chlorhexidine chewing gums on Streptococcus mutans
      counts--an in vivo microbiological study.
AB  - The aim of the present study was to evaluate the antimicrobial efficacy of
      Chlorhexidine chewing gums and to assess the effect of dosage and frequency of
      intake of Chlorhexidine gums on Streptococcus mutans (SM) count. METHOD: The
      sample consisted of 30 subjects, divided into two groups AI & AII. Each group
      consisted of 15 subjects. Group AI chewed 2 Chlorhexidine Chewing gum X Twice
      Daily for 20 minutes (Total = 4 gums Daily) & Group AII chewed 2 Chlorhexidine
      Chewing gum X Four times daily for 20 minutes (Total = 8 gums Daily) & saliva
      sample was collected & agar plates were inoculated for SM colony count. The study
      was carried for a week's time and salivary sample collected were Baseline, Day 1
      morning and evening, Day 4 evening, Day7 morning and evening. RESULTS: After the
      gum was chewed, it was observed that the colony count started to decrease when
      compared with baseline in both the groups. The fall in SM count was statistically
      highly significant with p < 0.001 in both the groups. When comparing between
      Group AI (Dosage 20 mg daily) and Group All (Dosage 40 mg daily), the fall in SM
      count for both the groups was not statistically significant with p-value > 0.05.
      It was concluded that there was reduction in the level of Salivary SM, but was
      not statistically significant, by increasing the dosage and frequency of intake
      of Chlorhexidine containing gums. CONCLUSIONS: We recommend that dosage of
      Chlorhexidine containing chewing gums can be restricted to four gums instead of
      eight gums per day.

PMID- 21189762
TI  - The pattern of maxillary canine impaction in relation to anomalous lateral
      incisors.
AB  - OBJECTIVE: To investigate the probability and pattern of maxillary canine
      impaction in relation to anomalous adjacent lateral incisors. SUBJECTS AND
      METHOD: A total 66 patients (M=24, F=42) in the age range of 12 to 18 years who
      had at least one impacted maxillary canine were included for the study. The
      maxillary lateral incisor anomalies and nature of canine impactions were
      diagnosed from the radiographs and study models. Maxillary lateral incisors were
      classified as normal, peg shaped, impacted and congenitally missing. The
      maxillary canine impactions were classified as buccal and palatal impaction. Each
      affected maxillary side was considered separately. This resulted total 88 cases
      for which the probabilities of different canine positions adjacent to the
      different categories of lateral incisor anomalies were evaluated statistically.
      RESULTS: : The occurrence of palatal canine impaction was almost 1.6 times more
      than the buccal canine impaction. Total 11.76% of the bucally impacted canines
      and 38.89% of the palatally impacted canines were associated with anomalous
      lateral incisors. There was no positive association between anomalous lateral
      incisors and maxillary canines. In relation to anomalous lateral incisor, the
      probability of palatal canine impaction was more than the buccal canine
      impaction. CONCLUSIONS: There was no positive association between lateral incisor
      anomalies and maxillary canine impaction. However, there was a high probability
      of palatal canine impaction when adjacent lateral incisors were anomalous.

PMID- 21189763
TI  - Relationship of dental caries at different concentrations of fluoride in endemic
      areas: an epidemiological study.
AB  - OBJECTIVE: Fluoride has been an effective tool to prevent dental caries but
      efforts have been on to establish optimal level of fluoride in drinking water in
      different communities. The present study seeks to establish the safe and
      acceptable concentration of fluoride in drinking water which would lead to
      maximum caries protection with least amount of clinically observable dental
      fluorosis. STUDY DESIGN: 30 villages from 2 districts of Haryana were classified
      according to differing levels of fluoride in the drinking water. 3007 school
      children (1558 males & 1449 female)] were examined and the DMFT score was related
      to the level of fluoride in drinking water. RESULTS: The caries prevalence was
      maximum (48.02%) in the area having 0.50 ppm fluoride in drinking water The
      children from area having the 1.13 ppm fluoride level had the least caries
      prevalence i.e. 28.07%. CONCLUSION: The results of the present study did not
      suggest any additional anticaries benefit beyond 1.13 ppm fluoride level. The
      present investigation showed that the optimalfluoride levels for drinking water
      for our conditions were near 1.13ppm (1-1.2 ppm) as there was maximum caries
      protection with least amount of esthetically objectionable fluorosis at that
      level.

PMID- 21189764
TI  - Resin replica in enamel deproteinization and its effect on acid etching.
AB  - PURPOSE: The goal of this in vitro study was to identify the topographical
      features of deproteinized (NaOCl) and etched with phosphoric acid (H3PO4) enamel
      surface, compared to phosphoric acid surface alone with a Resin Replica model.
      MATERIALS: Ten extracted lower first and second permanent molars were polished
      with pumice and water, and then divided into 3 equal buccal sections having
      similar physical and chemical properties. The enamel surfaces of each group were
      subjected to the following treatments: Group A: Acid Etching with H3PO4 37% for
      15 seconds. Group B: Sodium Hypochlorite (NaOCl) 5.25% for 60 seconds followed by
      Acid Etching with H3PO4 37% for 15 seconds. Group C; No treatment (control). All
      the samples were treated as follow: Adhesive and resin were applied to all groups
      after A, B and C treatment were performed; Then enamel/dentin decalcification and
      deproteinization and topographic SEM Resin Replica assessment were used to
      identify resin tags enamel surface quality penetration. RESULTS: Showed that
      group B reached an area of 7.52 mm of the total surface, with a 5.68 mm2 (73%)
      resin tag penetration equivalent type I and II etching pattern, 1.71 mm2 (26%)
      equivalent to type III etching pattern and 0.07 mm2 (1%) unaffected surface.
      Followed by group A with 7.48 mm2 of the total surface, with a 3.47 mm2 (46
      %)resin tag penetration equivalent to type I and II etching pattern, 3.30 mm2
      (45%)equivalent to type III etching pattern and 0.71 mm2, and (9%) unaffected
      surface. Group C did not show any resin tag penetration. A significant
      statistical diference (P < 0.001) existed between groups A and B in resin quality
      penetration, leading to the conclusion that when the enamel is deproteinizated
      with 5.25% NaOCl for 1 minute prior H3PO4, the surface and topographical features
      of the replica resin penetration surface increases significantly with type I-II
      etching pattern.

PMID- 21189765
TI  - Dental pulp stem cells from primary and permanent teeth: quality analysis.
AB  - OBJECTIVE: The objective of the study was to identify and isolate stem cells from
      healthy and inflamed dental pulp and characterize their differentiation potential
      into multiple lineages. STUDY DESIGN: Study was conducted in dental pulp tissues
      obtained from the children in the age range of 5-14 years. Tissue samples were
      collected from teeth indicated for pulp therapy and extractions for orthodontic
      purpose. Samples were processed in the laboratory including cell culture,
      isolation and differentiation into multiple lineages. The results for the
      analysis of various cell surface markers used for dental pulp were compared with
      bone marrow which is considered as a gold standard. RESULTS: There was no
      statistically significant difference found in the expression of various surface
      markers between inflamed dental pulp and bone marrow. Healthy pulp from the
      primary teeth was not sufficient to use as a source for harvesting stem cells
      moreover the healthy tissue obtained from permanent teeth failed to show any
      results at all. CONCLUSION: Inflamed pulp discarded during pulp therapy
      procedures is a potential source for harvesting adult stem cells.

PMID- 21189766
TI  - Evaluation of knowledge, attitudes, and self-reported behaviors among 3-5 year
      old school children using an oral health and nutrition intervention.
AB  - METHODS: Ninety 3-5 year old children, 43 in the control group and 47 in the
      intervention group, participated in the study. An age and developmental
      appropriate prop-based oral health and nutrition intervention program was used.
      Subjects in the intervention group received a pre-test, an 8-10 minute prop
      supported intervention, followed by an immediate post-test. The same test was
      repeated two weeks later The control group received a pre-test and post-test two
      weeks later but no intervention. RESULTS: Intervention improved scores in the
      immediate post-test but these improvements were not sustained two weeks later The
      only positive relationship found for the entire group between pre-and two week
      post-test scores was for oral health knowledge. There were no significant
      findings when adjusted for race, intervention type or group. CONCLUSIONS:
      Changing oral health and nutrition knowledge, attitude and behavior may require
      intense and repetitive interventions to have a significant effect in this age
      cohort.

PMID- 21189767
TI  - In vitro determination of the chromatic effect of a silver nanoparticles solution
      linked to the gantrez S-97 copolymer on tooth enamel.
AB  - Silver nanoparticles (NNPs), alone or in combination with the bioadhesive Gantrez
      S-97, have demonstrated their efficacy against Streptococcus mutans; however, it
      is not known if this combination changes the color of teeth. The aim of this work
      was to measure the color changes occurring after the use of a Gantrez-NNP
      combination on enamel tooth blocks. Two study groups were randomly formed: enamel
      blocks brushed with (a) the Gantrez-NNP combination and (b) conventional
      toothpaste, for 1 minute once daily for 4 weeks, then rinsed with distilled water
      and placed in thymol solution. Color changes in the enamel blocks were measured
      using a Minolta colorimeter CR300. Analysis of mixed models was performed with R
      2.10.1 at a 95% confidence level, using the nonlinear mixed effects (NLME)
      package. The results showed that there were no color changes over time, only a
      high luminosity equal in both groups. Our study showed that the use of the
      Gantrez-NNP combination is safe with respect to dental esthetics in the control
      of S. mutans.

PMID- 21189768
TI  - Genotoxic effects of dental panoramic radiograph in children.
AB  - This study was completed to evaluate chromosomal damage (micronucleus) and
      cellular death in exfoliated buccal mucosa cells taken from healthy children
      following exposure to panoramic radiation during dental radiography. METHOD:
      Twenty children who underwent panoramic dental radiography for diagnostic
      purposes were included. Cytological preparations were stained with Feulgen stain,
      identified under light microscopy. Micronuclei, apoptotic nuclear alterations
      (condensed chromatin, karyorrhexis, pyknosis) and necrosis (karyolysis) were
      scored. RESULTS: showed no statistically significant differences in children's
      micronucleated oral mucosa cells before and after panoramic dental X-Ray
      exposure. On the other hand, there was a statistically significant increase in
      nuclear alterations closely related to genotoxicity such as condensed chromatin,
      karyorrhexis and pyknosis, while karyolysis of oral mucosal cells did not show
      significant increase after panoramic X-Ray exposure. CONCLUSION: Dental panoramic
      radiography may not be a factor that induces chromosomal damage, but is able to
      promote genotoxicity in children.

PMID- 21189769
TI  - Removal of organic debris from occlusal fissures: advantage of Carisolv system
      over sodium hypochlorite.
AB  - OBJECTIVE: The purpose of this in vitro study was to evaluate and compare the
      removal of artificial debris from pits and fissures using the Carisolv system and
      sodium hypochlorite. STUDY DESIGN: Forty artificial fissures prepared on
      extracted human teeth were filled with artificial organic debris. Debris was
      removed using either Carisolv or 10% sodium hypochlorite gel. After stereoscopic
      observation, samples were filled with a sealant and subjected to microleakage
      test. RESULTS: Both Carisolv and sodium hypochlorite demonstrated adequate
      cleaning ability and prevention of microleakage. Although both Carisolv and 10%
      sodium hypochlorite are effective at removing debris from fissures, Carisolv
      presents greater advantages in terms of safety and antibacterial properties.
      CONCLUSION: Fissure cleaning using Carisolv might be an effective approach to
      improve the retention of fissure sealants.

PMID- 21189770
TI  - Efficacy of platelet-rich-plasma (PRP) in bone regeneration after cyst
      enucleation in pediatric patients--a clinical study.
AB  - BACKGROUND: Platelet-rich-plasma (PRP) is a type of natural source of autologous
      growth factors, and has been used successfully in various fields. However the use
      ofPRP in children is not well documented. OBJECTIVE: To evaluate the efficacy of
      adding PRP to a bone graft in the bone regeneration of cystic bony defects
      following cystectomy. STUDY DESIGN: Study sample included 20 children who were
      randomly divided into two groups with 10 patients in each group; all underwent
      cystectomy In the first group (test group), after cystectomy the cystic defect
      was filled with PRP and bone graft. In the second group (control group) bone
      graft alone (without PRP) was used. Radiographs were recorded at 1 month, 2
      months, 4 months and 6 months intervals after surgery to evaluate the defect bone
      fill in both groups. RESULTS: The post-operative successive radiographs in the
      test group showed a significantly greater regeneration of bone in the height of
      bony defects with application of PRP to bone graft as compared to the control
      group. In the test group, by the first post operative month, about 58% of the
      defect was filled, which gradually increased in each month and showed about 94%
      of defect-fill by 6 months. In the control group, similar observation revealed
      only 31% of defect-fill by the first post-operative month and a 47% defect-fill
      at 6 months. CONCLUSION: The addition of PRP to bone graft appeared to enhance
      bone regeneration considerably. The combination of PRP and bone graft might have
      a potential for routine clinical use for regeneration of cystic bony defects in
      children.

PMID- 21189771
TI  - Oral carcinoma cuniculatum in a young child.
AB  - From the Department of Dental Specialties, Birmingham Children's Hospital. This
      case study describes a rare case of oral carcinoma cuniculatum in a 7-year-old
      female. She presented with an enlarged mass of the anterior maxilla arising from
      the gingiva. An anterior maxillectomy with immediate prosthetic replacement and
      obturation of the residual defect were carried out. The management of this case
      was challenging given the rare nature of the disease, unclear etiology, the
      patient's young age and the mutilating effects of surgery. The treatment involved
      a large multidisciplinary team. The provision of obturators was particularly
      difficult due to poor patient compliance and the extent of surgery carried out in
      a growing child. Oral cancer in children under 15 years old is extremely rare and
      this is the youngest case of oral carcinoma cuniculatum reported in the
      literature.

PMID- 21189772
TI  - Nevoid basal cell carcinoma syndrome presenting with neck pits and cafe au lait
      patches.
AB  - BACKGROUND: A 10- year-old patient presented with a slow growing jaw swelling.
      The initial general examination did not reveal any significant findings. METHODS:
      Conservative enucleation of the cyst confirmed it to be an odontogenic
      keratocyst. The patient remained asymptomatic for the following 2 years and
      subsequently presented cystic lesions in jaws with displaced teeth. These cysts
      were enucleated and were confirmed to be odontogenic keratocysts . The patient
      has been on regular follow up since then and subsequent scans have shown further
      occurrence of cysts in the jaws with displacement of the third molars. RESULTS:
      Clinical examination also revealed macrocephaly, fronto-parietal bossing, pitting
      on palmar and plantar surfaces, calcification of falx cerebri and splayed ribs,
      confirming the diagnosis of nevoid basal cell carcinoma syndrome. He also
      presented with a cafi au lait patch and skin pits on the neck. The family history
      was negative for features of nevoid basal cell carcinoma syndrome. CONCLUSION:
      Nevoid basal cell carcinoma syndrome is a condition that can cause significant
      morbidity if not detected early. Over the years this syndrome has presented with
      many other non specific phenotype presentation, of which the current finding may
      be one of This calls for meticulous assessment and examination of patients and a
      standardized protocol in screening and managing these patients that may
      facilitate a more beneficial outcome for the patient.

PMID- 21189773
TI  - Factor XIII deficiency: report of two cases.
AB  - Factor XIII deficiency is one of the rare clotting factor deficiencies. Although
      rare, it is an important disorder because of seriousness of its bleeding
      manifestations, in particular the incidence of intracranial hemorrhage is higher
      than any other bleeding disorder Hence an early diagnosis is extremely important
      where bleeding manifestations can be prevented by prophylactic factor XIII
      replacement given at every 4-6 week interval. Case1 presents the management of a
      factor deficiency associated with a very rare blood group AB+ve, while the case 2
      reports the successful surgical management with a replacement therapy

PMID- 21189774
TI  - Midazolam-fentanyl analgo-sedation in pediatric dental patients--a pilot study.
AB  - OBJECTIVE: The objective of this study was to comparatively evaluate the
      effectiveness ofsubmucosalfentanyl when administered in conjunction with oral
      midazolam during pediatric procedural sedations. STUDY DESIGN: Twenty three
      uncooperative ASA type I children who met the selection criteria were randomly
      assigned to receive either submucosal fentanyl (3 microg/kg) or placebo, along
      with oral midazolam (0.5 mg/kg). A triple blind, 2-stage cross-over design was
      adopted so that each child received both the regimens. RESULTS: Transient oxygen
      desaturation was observed in 4 children who were sedated with the combination of
      oral midazolam and submucosalfentanyl. The overall success was 73.91% with oral
      midazolam and submucosal fentanyl regimen and 47.83% for oral midazolam and
      submucosal placebo regimen. The chances of 'satisfactorily'completing a 45 minute
      dental procedure in an uncooperative pediatric patient was 2.8 times more, when
      submucosalfentanyl was used along with oral midazolam. CONCLUSION: Submucosal
      fentanyl appears to improve the short working time associated with oral
      midazolam. But the oxygen desaturation associated with this regimen necessitates
      further studies to evaluate the efficacy of this combination at relatively lower
      doses before being used routinely for pediatric procedural sedation and
      analgesia.

PMID- 21189775
TI  - Dental and skeletal changes in the upper and lower jaws after treatment with
      Schwarz appliances using cone-beam computed tomography.
AB  - OBJECTIVE: The purpose of this research was to use cone-beam computed tomography
      (CBCT) images to evaluate dental and skeletal changes in upper and lower jaws
      after treatment with Schwarz appliances. MATERIALS AND METHODS: 28 patients with
      Angle Class I molar relationships and crowding were randomly divided into two
      groups--14 non-expanded and 14 expanded patients. 3D-Rugle CBCT software was used
      to measure various reference points before treatment (TO) and during the
      retention period of approximately 9 months after 6 to 12 month expansion (T1).
      Cephalometric and cast measurements were used to evaluate treatment in both
      groups. To test whether there were any significant differences between the
      control and treatment groups at TO and T1, the Mann-Whitney U-test was used.
      RESULTS: The dental arch (including tooth root apices) had expanded in the upper
      and lower jaws. Alveolar bone expansion of up to 2 mm apical to the cementoenamel
      junction (CEJ) was detected. The midpalatal sutures were separated in some cases
      and subsequent expansion was observed at the inner surface of the nasal cavity at
      the inferior turbinates. However no significant (P > 0.05) difference was
      observed in the inter-width of the mandibular bodies, zygomatic bones, nasal
      cavity in the middle turbinate region, condylar heads, or antegonial notches. In
      mandibular and maxillary cast measurements, arch crowding and arch perimeter
      showed statistically significant changes in the expansion group. The mandibular
      width values demonstrated no significant changes as measured from a point 2 mm
      apical to the CEJ whereas the maxillary width values demonstrated significant
      changes as measured from a point 2 mm apical to the CEJ. CONCLUSIONS: This study
      indicates that the Schwarz appliance primarily affects the dento-alveolar
      complex, while it has little effect on either the mandibular bodies, any
      associated structures including the maxillary midpalatal suture and the inter
      width of the nasal cavity in the middle turbinate region. In addition, the center
      of rotation of the mandibular and maxillary first molar was observed apical to
      the root apex.

PMID- 21189776
TI  - Identify exciting developments in marketing and communications.

PMID- 21189777
TI  - How will leading health care execs face the challenges ahead?

PMID- 21189778
TI  - New landscape requires expanded marketing leadership.

PMID- 21189779
TI  - All hospitals are not created eqyal. Yale-New Haven Hospital draws on its
      strengths to revitalize its brand.

PMID- 21189780
TI  - Empowering our own. Rebranding efforts reach out to a long-neglected population.

PMID- 21189781
TI  - A delicate balance. Dignity, honor, respect and the fourth estate.

PMID- 21189782
TI  - Connections that count.

PMID- 21189783
TI  - Healthy conversations. The supplement industry redefines itself.

PMID- 21189784
TI  - Dreams and machines.

PMID- 21189785
TI  - What keeps me awake. Meet patients where they are. Reform opens up a world of
      possibilities.

PMID- 21189786
TI  - NEHA's international perspective.

PMID- 21189787
TI  - A potential new health risk from lead in used consumer products purchased in the
      United States.
AB  - The Lead Renovation, Repair, and Painting Rule and the Consumer Product Safety
      Improvement Act, both enacted in 2008, were intended to protect children from
      exposure to lead by setting federal limits on lead content. Neither of these
      federal actions, however, addresses a newly recognized pathway of exposure to
      lead from the use of used consumer products in the home. In the study described
      in this article, the authors purchased 28 used consumer items in the United
      States in 2004 and analyzed them for lead content using X-ray fluorescence
      technology. Nineteen of the items exceeded the federal standards for lead. The
      amount of lead in the items ranged from 745 parts per million (ppm) to 428,525
      ppm. The authors' research shows that such items, which are easily purchased
      throughout the U.S., may contain surface lead concentrations in amounts greater
      than 700 times current federal limits. This article reveals an ongoing public
      health threat involved in exposure to lead that is not addressed by current laws
      or regulations. Addressing the risk involved in this threat requires continued
      research, public education, and targeted regulatory action.

PMID- 21189788
TI  - A synopsis of 30 years of major accomplishments by the Pennsylvania Department of
      Health in Environmental Health (Part 1 of 2): the 1980s.
AB  - This article reviews significant environmental health projects conducted by the
      Pennsylvania Department of Health, particularly the Division of Environmental
      Health, during the 1980s. The authors describe lessons learned from dealing with
      health concerns related to the Vietnam War, Three Mile Island, hazardous waste
      sites, and radon, as well as emerging issues during that decade.

PMID- 21189789
TI  - A synopsis of 30 years of major accomplishments by the Pennsylvania Department of
      Health in Environmental Health (Part 2 of 2): the 1990s and the 21st century.
AB  - This article reviews significant environmental health projects conducted by the
      Pennsylvania Department of Health, particularly the Division of Environmental
      Health, during the 1990s and the following decade. The authors describe lessons
      learned from a new occupational health initiative, continuing work on the health
      assessment grant funded by the Agency for Toxic Substances and Disease Registry,
      and a new Environmental Public Health Tracking grant funded by the Centers for
      Disease Control and Prevention, in addition to emerging issues during these two
      decades.

PMID- 21189790
TI  - Where have all the vector control programs gone? Part two.

PMID- 21189791
TI  - Larry Marcum celebrates 20 years with NEHA.

PMID- 21189792
TI  - Conducting business in a high tech world or ... why NEHA still has a
      receptionist!

PMID- 21189793
TI  - An "Ah-Ha moment".

PMID- 21189794
TI  - Emotional intelligence: the popular new seminar topic.

PMID- 21189795
TI  - Episcleritis and scleritis.
AB  - This article will briefly discuss episcleritis and scleritis as clinical
      entities. Both are forms of ocular inflammation but have different clinical,
      therapeutic and prognostic implications. Episcleritis is a self-limited disease,
      causing mild discomfort and infrequently requiring therapeutic intervention.
      Scleritis is a painful, inflammatory process, commonly associated with systemic
      disorders and requires systemic anti-inflammatory therapy. It is important to be
      able to distinguish between the two clinical conditions, as prompt initiation of
      therapy for scleritis can be sight saving.

PMID- 21189796
TI  - Mitomycin C--care and handling.

PMID- 21189797
TI  - Pediatric ophthalmology attire: should we wear a white coat?
AB  - The purpose of this study was to determine if patients and their families in a
      pediatric ophthalmology and adult strabismus clinic have a preference regarding
      physician and staffattire. Patients and/or parents were invited to complete a
      three-question survey. Respondents were queried based on three types of attire
      preference: white coat, professional clothing without white coat, or casual
      attire without white coat. Two hundred twenty-seven patients participated. Of the
      patients queried, no preference for any one style of physician attire was found.
      These results do not support previous studies indicating significant preference
      for white coats.

PMID- 21189798
TI  - Obtaining and verifying informed consent.

PMID- 21189799
TI  - Pain assessment for older adults.

PMID- 21189800
TI  - The role of the registered nurse in teaching phacoemulsification in developing
      nations.

PMID- 21189801
TI  - Pressure support ventilation and the ophthalmic surgical patient.

PMID- 21189802
TI  - Contrast sensitivity testing: when visual acuity testing alone is not enough.

PMID- 21189803
TI  - Developmental disorders and interventions. Preface.

PMID- 21189804
TI  - Poor working memory: impact and interventions.

PMID- 21189805
TI  - Mathematical learning disabilities.

PMID- 21189806
TI  - The poor comprehender profile: understanding and supporting individuals who have
      difficulties extracting meaning from text.

PMID- 21189807
TI  - Reading as an intervention for vocabulary, short-term memory and speech
      development of school-aged children with Down syndrome: a review of the evidence.

PMID- 21189808
TI  - Williams syndrome.

PMID- 21189809
TI  - Fragile X syndrome and associated disorders.

PMID- 21189810
TI  - Older people deserve better.

PMID- 21189811
TI  - Spending cuts:the real cost to staff and care.

PMID- 21189812
TI  - Board-level nurses have a tough challenge ahead. Interview by Tamsin Snow.

PMID- 21189813
TI  - Exciting the senses.
AB  - Deep brain stimulation can be a useful treatment for some patients with
      Parkinson's disease.

PMID- 21189814
TI  - The mark of responsibility.
AB  - A system to identify potential abusein small babies has been developed by a nurse
      and doctor in Hampshire.

PMID- 21189815
TI  - Choice agenda.
AB  - Personal health budgets are intended to allow people to set their own priorities
      and buy in services to meet them.

PMID- 21189816
TI  - A crucial safeguard.

PMID- 21189817
TI  - Work more, pay more, get less.

PMID- 21189818
TI  - Medicines management.

PMID- 21189819
TI  - Managing pain in the older person.
AB  - The UK population is ageing and a significant proportion of older people
      experience persistent pain. However, pain assessment in this group can be
      challenging, particularly when the older person has cognitive or communication
      impairment. Nurses working in primary and secondary care should take a more
      proactive role to help overcome patient, professional and institutional barriers
      to pain assessment and management. This article examines the age-related
      physiological changes that complicate the prescribing and administering of
      analgesic drugs in older patients and necessitate careful patient monitoring. It
      outlines the principles of medication administration for pain management in older
      people and provides examples of assessment tools that can be used in older
      patients.

PMID- 21189820
TI  - Measuring anxiety in surgical patients using a visual analogue scale.
AB  - Since the early days of surgery patients have been anxious about undergoing
      operations. This feeling remains common today despite advances in medicine and
      surgical techniques. Numerous studies have shown the effect anxiety has on the
      human body. It is the responsibility of healthcare professionals to ensure that
      any patient undergoing an elective surgical procedure is both physically and
      psychologically prepared. However, with increasing demands on the health service
      to be more efficient, little time is set aside to meet the psychological needs of
      the surgical patient. This article focuses on the use of a visual analogue scale
      to identify pre-operative anxiety in patients, so that healthcare practitioners
      can implement strategies to reduce anxiety and improve the person's overall
      experience.

PMID- 21189822
TI  - The mnemonic 'brain attack'.

PMID- 21189821
TI  - Nursing care of patients undergoing allogeneic stem cell transplantation.
AB  - Stem cell transplantation (SCT) may be a treatment option for patients who have
      been diagnosed with a haemato-oncological condition, such as leukaemia, lymphoma
      or multiple myeloma. SCT is a complex and challenging treatment. In particular,
      allogeneic transplant significantly increases the risk of developing infections.
      This article provides an overview of allogeneic SCT, discusses why infections are
      a major problem and highlights the role nurses play in preventing and managing
      established infections in this patient group.

PMID- 21189823
TI  - Recognising the signs.

PMID- 21189824
TI  - Degrees of learning.

PMID- 21189825
TI  - Step in the right direction.

PMID- 21189826
TI  - And yet another modest proposal.

PMID- 21189827
TI  - Organized medicine--why should physicians belong?

PMID- 21189828
TI  - Engaging patients and clinicians through a wellness portal to improve the health
      of Oklahomans.
AB  - Patient-centeredness is one of the key dimensions of the patient-centered medical
      home model, yet it is still not uniformly understood. A goal-directed care
      approach that incorporates active preparation and comprehensive patient visits
      has been suggested to empower patients and improve health outcomes by various
      resources, including patient-side health IT (e.g. portals). In the context of a
      recent randomized controlled trial funded by the Agency of Healthcare Research
      and Quality, we developed a patient Wellness Portal that was linked to a
      previously designed and implemented clinician-portal. A six-month pilot
      implementation study was followed by a 12-month randomized controlled trial to
      determine the impact of the Portal on patient and practice-level outcomes.
      Results indicate that the Wellness Portal was easy to use, well received by
      patients, helped users educate themselves about their conditions, gauge their
      health status, and create a longitudinal wellness plan for discussion during an
      annual wellness visit. A preliminary analysis also showed that a greater
      proportion of patients received preventive services in the Portal intervention
      group than in the control group.

PMID- 21189829
TI  - Breast cancer by stage of disease at diagnosis, central Oklahoma.
AB  - We describe factors associated with an initial diagnosis of stage IV breast
      cancer to identify segments of Oklahoma's population that need earlier screening.
      We obtained data from the Central Oklahoma chapter of Susan G. Komen for the Cure
      and from the Oklahoma Central Cancer Registry. All analyses were cross-sectional
      and ecologic. The distributions of breast cancer stage at diagnosis for ten
      central Oklahoma counties were analyzed with respect to age group,
      race/ethnicity, insurance status, family income, and the percent of women who
      reported [not] receiving a mammogram in the previous twelve months. The
      percentage of African American women diagnosed with stage IV disease (7.8%) was
      nearly double that in white (4.2%) and other races (4.1%; p < 0.01). After
      controlling for confounding variables, the proportion of women diagnosed with
      breast cancer at stage IV was still higher among African American than among
      white females (p < 0.01) and females aged 65+ years (p = 0.02). The availability
      of breast cancer screening services should be increased among African American
      women in central Oklahoma.

PMID- 21189831
TI  - Social networking and the medical practice.

PMID- 21189830
TI  - Do orally administered corticosteroids reduce acute sciatic pain in adults more
      than placebo? No.

PMID- 21189832
TI  - Exercise prescription for Iranian midlife women.
AB  - OBJECTIVES: The purpose of this study is to determine the effect of a multimodal
      intervention (including the Women's Wellness Program) on increasing levels of
      physical activity in Iranian midlife women. STUDY DESIGN: This 12-week study was
      conducted in women aged 50-65 years living in the general population. Women who
      were allocated to the intervention group (n = 40) received an intervention, which
      combined a multimodal program of physical activity and health education. Women in
      the control group continued their normal physical activities (n = 45). MEAN
      OUTCOME MEASURE: The women completed a questionnaire that included measures for
      items of interest for this analysis, such as menopausal status, sociodemographic,
      and exercise and activity levels. RESULTS: Analysis of covariance indicated that
      the intervention was effective in improving women's physical activity. The test
      showed that there was a significant difference between intervention and control
      in current vigorous activity. CONCLUSION: Physical activity should be encouraged
      for prevention and reduction of risks for chronic disease and for improvement of
      health in midlife women. The multimodal intervention program may offer
      implications for designing and implementing exercise interventions in further
      studies.

PMID- 21189834
TI  - Sertraline-induced pseudocholinesterase enzyme deficiency.
AB  - A 47-year-old Turkish male was scheduled for laparoscopic cholecystectomy under
      general anesthesia. The patient had 2 operations 28 and 19 years ago under
      general anesthesia. It was learned that the patient was administered
      succinylcholine during both of these previous operations and that he did not have
      a history of prolonged recovery or postoperative apnea. The patient had been
      using sertraline for 3 years before the operation. Pseudocholinesterase is a drug
      metabolizing enzyme responsible for hydrolysis of the muscle-relaxant drugs
      mivacurium and succinylcholine. Deficiency of this enzyme from any cause can lead
      to prolonged apnea and paralysis following administration of mivacurium and
      succinylcholine. The diagnosis of pseudocholinesterase enzyme deficiency can be
      made after careful clinic supervision and peripheral nerve stimulator monitoring.
      A decrease in the activity of pseudocholinesterase enzyme and a decline in the
      block effect over time will help verify the diagnosis. Our patient's plasma
      cholinesterase was found to have low activity. Instead of pharmacological
      interventions that may further complicate the situation in such cases, the
      preferred course of action should be to wait until the block effect declines with
      the help of sedation and mechanical ventilation. In our case, the prolonged block
      deteriorated in the course of time before any complications developed.

PMID- 21189833
TI  - Are Doppler ultrasonography parameters symmetric between the right and left
      kidney?
AB  - BACKGROUND: Among numerous modalities applied for evaluation of kidney diseases,
      Doppler ultrasonography (DU) provides information about the hemodynamic status of
      the kidneys. Meanwhile, the variability in DU parameters of the right and left
      kidney is a matter of controversy. The aim of this study was to determine whether
      any difference exists between the DU indices of the right and left kidney.
      METHODS: Retrospectively, we collected DU findings of 25 healthy potential renal
      transplant donors. All donors underwent renal DU and multidetector computed
      tomographic angiography before donor nephrectomy. DU indices, including peak
      systolic volume (PSV), resistive index (RI), pulsatility index (PI), end
      diastolic volume (EDV), and acceleration time (AT), were recorded. RESULTS: The
      median age of the donors was 27 (range 23-39) years. The median PSV, RI, EDV, and
      AT for the right kidney were 29 cm/sec, 0.59, 10.9 cm/sec, and 50 msec,
      respectively. For the left kidney, the median PSV, RI, EDV, and AT were,
      respectively, 26.8 cm/sec, 0.60, 10.6 cm/sec, and 43 msec. Among the DU indices,
      median PI of the right kidney was significantly different from that of the left
      kidney (1.02 versus 0.95, P = 0.01). CONCLUSION: In conclusion, the present study
      revealed that right kidney DU indices, except for PI, may not differ from those
      of the left kidney.

PMID- 21189835
TI  - Use of the Joint British Society cardiovascular risk calculator before initiating
      statins for primary prevention in hospital medicine: experience from a large
      university teaching hospital.
AB  - INTRODUCTION: Statin therapy is a well established treatment for hyperlipidemia.
      However, little is known about prescribing of statins for primary prevention in
      the real world, and even less about what happens to patients requiring primary
      prevention who are seen in a secondary care setting. The purpose of this research
      was to investigate the appropriateness of statin prescriptions by using the Joint
      British Society cardiovascular disease (JBS CVD) risk score for primary
      prevention in a large secondary care center. METHODS: We retrospectively analyzed
      500 consecutive patients in whom a statin prescription was initiated over a four
      month period. We excluded patients who met secondary prevention criteria. We used
      the JBS CVD risk prediction chart to calculate 10-year composite risk. We also
      studied which statins were prescribed and their starting doses. RESULTS: Of 500
      patients consecutively started on statins in secondary care, 51 patients (10.2%)
      were treated for primary prevention. Of these, seven (14%) patients had a 10-year
      composite cardiovascular event risk of more than 20% (high-risk category), and
      were hence receiving appropriate therapy. Three main statins were prescribed for
      primary prevention, ie, atorvastatin (22 patients, 43%), simvastatin (25
      patients, 49%), and pravastatin (four patients, 8%). The statins prescribed were
      initiated mainly at the 40 mg dose. CONCLUSIONS: Statin prescribing in secondary
      care for primary prevention is limited to about 10% of initiations. There is some
      overprescribing, because 86% of these patients did not require statins when risk
      stratified appropriately. The majority of the prescriptions were for simvastatin
      40 mg and atorvastatin 40 mg.

PMID- 21189836
TI  - Duodenal administered seal oil for patients with subjective food
      hypersensitivity: an explorative open pilot study.
AB  - Short-term duodenal administration of n-3 polyunsaturated fatty acid (PUFA)-rich
      seal oil may improve gastrointestinal complaints in patients with subjective food
      hypersensitivity, as well as joint pain in patients with inflammatory bowel
      disease (IBD). The aim of the present explorative pilot study was to investigate
      whether 10-day open treatment with seal oil, 10 mL self-administrated via a
      nasoduodenal tube 3 times daily, could also benefit nongastrointestinal
      complaints and quality of life (QoL) in patients with subjective food
      hypersensitivity. Twenty-six patients with subjective food hypersensitivity, of
      whom 25 had irritable bowel syndrome (IBS), were included in the present study.
      Before and after treatment and 1 month posttreatment, patients filled in the
      Ulcer Esophagitis Subjective Symptoms Scale (UESS) and the Gastrointestinal
      Symptom Rating Scale (GSRS) for gastrointestinal symptoms and subjective health
      complaints (SHC) inventory for nongastrointestinal symptoms in addition to short
      form of the Nepean dyspepsia index (SF-NDI) for evaluation of QoL. Compared with
      baseline, gastrointestinal, as well as nongastrointestinal, complaints and QoL
      improved significantly, both at end of treatment and 1 month posttreatment. The
      consistent improvements following seal oil administration warrant further placebo
      controlled trials for confirmation of effect.

PMID- 21189837
TI  - Endobronchial valves: an emerging therapeutic alternative to VATS for the
      surgical management of advanced emphysema.

PMID- 21189838
TI  - Unresolved abdominal mass in an adult cryptorchid testis: a case report.
AB  - This case study aims to report an unresolved abdominal mass in an adult with
      cryptorchid testis and provide a review of related literature. We investigated a
      54-year-old man who had cryptorchidism with a history of left orchiectomy 18
      years prior. He was diagnosed with an intra-abdominal testicular mass after
      referring to the emergency ward with pelvic pain. The incidence of testicular
      cancer in undescended testicles is 40 times greater in the general population. In
      developed countries, the existence of undescended testicles in adult population
      is rare, which could be due to systematic practice of elective orchidopexy before
      the second year of life as well as orchiectomy in post-adolescent patients with
      undescended testicles. Despite these preventive measures, there are still some
      isolated cases of intra-abdominal testicular tumors in adults.

PMID- 21189839
TI  - A 25-year trace of methicillin-resistant Staphylococcus aureus dissemination in a
      geriatric hospital in Japan.
AB  - We analyzed 218 strains of methicillin-resistant Staphylococcus aureus (MRSA)
      isolated from the septicemia patients in a geriatric hospital for 25 years. These
      strains were classified into 11 major DNA types, A through K, and 27 minor types.
      The strains belonging to group A and B isolated before 1990 were susceptible to
      imipenem (IPM), fluoroquinolone, and most other antibiotics tested, except that
      they were markedly resistant to gentamicin. Strains mostly isolated in 1985 and
      thereafter were classified into group C through K, and they were mainly resistant
      to IPM, fluoroquinolones, and clindamycin. Analysis of the MRSA marker gene,
      staphylococcal cassette chromosome mec (SCCmec), of these strains revealed that
      the strains in groups A and B had mainly type IV and type I, respectively, and
      that strains in groups C through J had mainly type II. These results suggested
      that the strains holding type II SCCmec were resistant to IPM, fluoroquinolone,
      and clindamycin and they were dominant-resistant type after late 1980s. The
      antibiotic resistance profiles of MRSA dramatically changed during late 1980s,
      and these were correlated with the SCCmec types. The lesson from this study would
      be that consistent execution of surveillance study is needed to update the
      resistant profiles.

PMID- 21189840
TI  - Informatics methods for laboratory evaluation of HPV ordering patterns with an
      example from a nationwide sample in the United States, 2003-2009.
AB  - BACKGROUND: Laboratory data is a rich source of information that can be used to
      estimate adherence to physician guidelines and motivate improvement in clinical
      practice. Human papillomavirus (HPV) testing is an important component of
      cervical cancer screening programs with established screening guidelines. The
      purpose of this study was to develop methods to estimate concordance with
      published guidelines for HPV testing in order to provide clinicians and payors
      specific feedback about overscreening. METHODS: This retrospective analysis of
      laboratory test ordering patterns evaluated 454,532 HPV tests ordered from
      September 2003 to October 2009 from 110 facilities and performed at ARUP
      laboratories. We used laboratory data including patient demographics, ordering
      frequency, timestamps and results to examine the proportion of HPV tests ordered
      on women under 21 years, ordered on women between 21 and 29 years apparently
      before cytological examination, repeated less than 1 year after a positive HPV
      result in women over 30 years, and repeated less than 3 years after a negative
      HPV result in women over 30 years. RESULTS: The absolute number and proportion of
      HPV tests performed on women under 21 years declined from 20% in 2005 to 5% in
      October 2009. The proportion of HPV tests performed women between 21 and 29 years
      also declined during this period. Approximately one-third of HPV tests performed
      on women between 21 and 29 years arrived for HPV testing before cervical
      screening had presumably been completed. The most common follow-up intervals for
      HPV testing on women over 30 years were 6 months following a positive HPV result
      and 12 months following a negative HPV result. Only 6% of repeat HPV testing in
      women over 30 years followed a negative HPV result by 3 years or more.
      Approximately one-fourth of HPV tests ordered the year ending October 2009 were
      unnecessary based on the American Society for Colposcopy and Cervical Pathology
      guideline. CONCLUSIONS: We demonstrate simple methods to evaluate appropriate
      utilization of HPV testing using laboratory data. Our data illustrates that some
      aspects of HPV test ordering have become more consistent with guidelines over
      time. However, a large portion of HPV testing in the United States is
      unnecessary. This highlights opportunities for optimization of a rational cancer
      prevention strategy to reduce unnecessary screening, colposcopy and biopsies.

PMID- 21189841
TI  - Engineering a novel self-powering electrochemical biosensor.
AB  - This paper records the efforts of a multi-disciplinary team of undergraduate
      students from Glasgow University to collectively design and carry out a 10 week
      project in Synthetic Biology as part of the international Genetic Engineered
      Machine competition (iGEM). The aim of the project was to design and build a self
      powering electrochemical biosensor called 'ElectrEcoBlu'. The novelty of this
      engineered machine lies in coupling a biosensor with a microbial fuel cell to
      transduce a pollution input into an easily measurable electrical output signal.
      The device consists of two components; the sensor element which is modular,
      allowing for customisation to detect a range of input signals as required, and
      the universal reporter element which is responsible for generating an electrical
      signal as an output. The genetic components produce pyocyanin, a competitive
      electron mediator for microbial fuel cells, thus enabling the generation of an
      electrical current in the presence of target chemical pollutants. The pollutants
      tested in our implementation were toluene and salicylate. ElectrEcoBlu is
      expected to drive forward the development of a new generation of biosensors. Our
      approach exploited a range of state-of-the-art modelling techniques in a unified
      framework of qualitative, stochastic and continuous approaches to support the
      design and guide the construction of this novel biological machine. This work
      shows that integrating engineering techniques with scientific methodologies can
      provide new insights into genetic regulation and can be considered as a reference
      framework for the development of biochemical systems in synthetic biology.

PMID- 21189842
TI  - The GeneOptimizer Algorithm: using a sliding window approach to cope with the
      vast sequence space in multiparameter DNA sequence optimization.
AB  - One of the main advantages of de novo gene synthesis is the fact that it frees
      the researcher from any limitations imposed by the use of natural templates. To
      make the most out of this opportunity, efficient algorithms are needed to
      calculate a coding sequence, combining different requirements, such as adapted
      codon usage or avoidance of restriction sites, in the best possible way. We
      present an algorithm where a "variation window" covering several amino acid
      positions slides along the coding sequence. Candidate sequences are built
      comprising the already optimized part of the complete sequence and all possible
      combinations of synonymous codons representing the amino acids within the window.
      The candidate sequences are assessed with a quality function, and the first codon
      of the best candidates' variation window is fixed. Subsequently the window is
      shifted by one codon position. As an example of a freely accessible software
      implementing the algorithm, we present the Mr. Gene web-application. Additionally
      two experimental applications of the algorithm are shown.

PMID- 21189843
TI  - Processing DNA molecules as text.
AB  - Polymerase Chain Reaction (PCR) is the DNA-equivalent of Gutenberg's movable type
      printing, both allowing large-scale replication of a piece of text. De novo DNA
      synthesis is the DNA-equivalent of mechanical typesetting, both ease the setting
      of text for replication. What is the DNA-equivalent of the word processor?
      Biology labs engage daily in DNA processing-the creation of variations and
      combinations of existing DNA-using a plethora of manual labor-intensive methods
      such as site-directed mutagenesis, error-prone PCR, assembly PCR, overlap
      extension PCR, cleavage and ligation, homologous recombination, and others. So
      far no universal method for DNA processing has been proposed and, consequently,
      no engineering discipline that could eliminate this manual labor has emerged.
      Here we present a novel operation on DNA molecules, called Y, which joins two DNA
      fragments into one, and show that it provides a foundation for DNA processing as
      it can implement all basic text processing operations on DNA molecules including
      insert, delete, replace, cut and paste and copy and paste. In addition,
      complicated DNA processing tasks such as the creation of libraries of DNA
      variants, chimeras and extensions can be accomplished with DNA processing plans
      consisting of multiple Y operations, which can be executed automatically under
      computer control. The resulting DNA processing system, which incorporates our
      earlier work on recursive DNA composition and error correction, is the first
      demonstration of a unified approach to DNA synthesis, editing, and library
      construction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this
      article (doi:10.1007/s11693-010-9059-y) contains supplementary material, which is
      available to authorized users.

PMID- 21189844
TI  - Critical incident reporting system: Is it the solution?

PMID- 21189845
TI  - Medical liability litigation in Saudi Arabia.
AB  - BACKGROUND: The author analyzed the anesthesia medical malpractice closed claims
      that were referred to the Legal Health Organization (LHO) in order to evaluate
      the magnitude and underlying factors of the problem in Saudi Arabia. MATERIALS
      AND METHODS: Annual reports covering the period from 1420H-1429H (1999-2008) were
      statistically analyzed to give mean figures and percentages in each annual
      report, and then demonstrated all together to run the differential analysis
      together with the trend along the studied period. RESULTS: Data analysis showed
      an escalating trend for the total number of claims over the study period being
      started with 440 cases on 1420H and ended with 1356 cases by the year 1429H. The
      annual percentage of the final verdicts of accusation to the total number of
      claims presented to all committees ranges between 45.5%-60.2% with a mean value
      of 49.9%. Distribution of final verdicts among different clinical specialities
      showed that obstetrics takes the lead with a mean percentage of 25.5% along the
      studied period (1420H-1429H), followed by the practice of general surgery with a
      mean percentage of 13.8%. The sector of health care service showed a significant
      variation in relation to the mean number of final verdicts with accusation along
      the studied period, being the highest in the Ministry of Health sector with a
      mean number of 216.8 claims, followed by the private sector with a mean number of
      197.3 claims. CONCLUSION: Adherence to the standards of medical practice is by
      far to the best approach to avoid and reduce the incidence of litigation.

PMID- 21189846
TI  - Evaluation of the surgical factor in postoperative pain control.
AB  - BACKGROUND: Postoperative pain control has been studied extensively, including
      many perioperative pain control procedures. Unfortunately, the impact of the
      surgical technique was not objectively studied. AIM: The aim of this study is to
      evaluate if the type of surgical dissection needed for extensive abdominal wall
      dissection actually has an effect in the reduction of postoperative pain or not.
      MATERIALS AND METHODS: Forty adult patients, 19 males and 21 females, were
      randomly divided into two groups with each group containing 20 patients having
      different varieties of anterior abdominal wall ventral hernia. Patients in group
      I had their hernias and abdominal wall flaps dissected by only sharp dissection
      using scalpel. Patients in group II had their hernias and abdominal wall flaps
      dissected using mainly blunt dissection assisted by sharp dissection where blunt
      dissection could not do the job. All the patients had general anesthesia. No
      preemptive analgesia was used. Nalbufen was used as the only postoperative pain
      killer and the total amount used of it was treated as the indicator for the
      intensity of postoperative pain. RESULTS: The results of the present study showed
      that the total amount of Nalbufen used for the control of postoperative pain is
      significantly less in group I throughout the postoperative follow-up period.
      CONCLUSION: This study concludes that use of sharp dissection in cases of
      extensive abdominal wall dissection is statistically better than other methods of
      dissection in terms of postoperative pain control.

PMID- 21189847
TI  - Comparative study between I-gel, a new supraglottic airway device, and classical
      laryngeal mask airway in anesthetized spontaneously ventilated patients.
AB  - OBJECTIVE: To compare two different supraglottic airway devices, the laryngeal
      mask airway (LMA) and the I-gel, regarding easiness of insertion of the device,
      leak pressure, gastric insufflation, end tidal CO(2), oxygen saturation,
      hemodynamic and postoperative complications in anesthetized, spontaneously
      ventilated adult patients performing different non-emergency surgical procedures.
      MATERIALS AND METHODS: The study was carried out as a prospective, randomized,
      clinical trial among 80 patients who underwent different surgical procedures
      under general anesthesia with spontaneous ventilation in supine position. They
      were equally randomized into two groups: I-gel and LMA groups. Both the devices
      were compared with regard to heart rate, arterial BP, SPO(2), end-tidal CO(2),
      number and duration of insertion attempts, incidence of gastric insufflation,
      leak pressure and airway assessment after removal of the device. RESULTS: No
      statistically significant difference was reported between both the groups,
      regarding heart rate, arterial BP, SPO(2) and end-tidal CO(2). The mean duration
      of insertion attempts was 15.6+/-4.9 seconds in the I-gel group, while it was
      26.2+/-17.7 seconds in the LMA group. The difference between both the groups
      regarding duration of insertion attempts was statistically significant
      (P=0.0023*), while the number of insertion attempts was statistically
      insignificant between both the study groups (P>0.05). Leak pressure was (25.6+/
      4.9 vs. 21.2+/-7.7 cm H(2)O) significantly higher among studied patients of the I
      gel group (P=0.016*) and the incidence of gastric insufflation was significantly
      more with LMA group 9 (22.5%) vs. I-gel group (5%) (P=0.016). CONCLUSION: Both
      LMA and I-gel do not cause any significant alteration in the hemodynamic status
      of the patients, end tidal CO(2), and SPO(2). The postoperative complications
      were not significantly different except nusea and vomiting was statistically
      significant higher in LMA group (P=0.032). among both LMA and I-gel patients.
      Insertion of I-gel was significantly easier and more rapid than insertion of LMA.
      Leak pressure was significantly higher with I-gel than LMA and thus incidence of
      gastric insufflation was significantly lower with I-gel.

PMID- 21189848
TI  - Study of the effect of oral gabapentin used as preemptive analgesia to attenuate
      post-operative pain in patients undergoing abdominal surgery under general
      anesthesia.
AB  - AIMS: To study the effect of oral gabapentin used as preemptive analgesia to
      attenuate post operative pain in patients undergoing abdominal surgery under
      general anesthesia. MATERIALS AND METHODS: In a randomized double blind study, 60
      patients were divided into two groups. Group A received 600mg gabapentin and
      group B oral received placebo 1 h prior to surgery. Anesthesia was induced with
      Propofol 2 mg/kg and Vecuronium 0.1mg/kg and maintained with 60% N(2)O in O(2)
      and Vecuronium 0.02 mg/kg. All cases were given Fentanyl 2ug/kg as pre medication
      and a repeat dose 1ug/kg at the end of the first hour. Assessment of post
      operative pain was made with the visual analog score (VAS) at extubation (0 h),
      2, 4, 6, 12, and 24 h post-operatively. Post-operative analgesia was provided
      with intravenous Tramadol. The first dose was given in the Post Anesthesia Care
      Unit as 2mg/kg, and repeated at 8 and 16 h. Rescue analgesia was given with
      Diclofenac 1.5mg/kg, slow intravenous. The number of doses of rescue analgesia in
      both the groups was noted. RESULTS: The VAS scores at 0, 2, 4, 6, 12, and 24 h
      were 1.9 vs. 2.4 (P=0.002), 2.3 vs. 3.0 (P=0.000), 3.2 vs. 3.7 (P=0.006), 2.9 vs.
      4.4 (P=0.000), 3.6 vs. 4.6 (P=0.000), and 3.7 vs.4.6 (P=0.000), respectively.
      Numbers of patients requiring rescue analgesia with Diclofenac were 3 vs. 14
      (P=0.004). CONCLUSION: A single oral dose of gabapentin given pre-operatively
      enhanced the analgesic effect of Tramadol as it also reduced the requirement of
      rescue analgesia with Diclofenac.

PMID- 21189849
TI  - Electrolyte changes: An indirect method to assess irrigation fluid absorption
      complications during transurethral resection of prostate: A prospective study.
AB  - CONTEXT: Fluid absorption is inevitable complication of transuretheral resection
      of prostate and serum electrolytes changes can indirectly assess the irrigation
      fluid absorption. AIMS: To monitor the extent of 1.5% glycineirrigation fluid
      absorption during transurethral resection of prostate (TURP), by measuring the
      changes of serum sodium and potassium levels peri-operatively. SETTINGS AND
      DESIGN: This is a randomized prospective cohort observational study. MATERIALS
      AND METHODS: The 86 male patients of ASA grades I to III in the age group of 50
      to 80 years, scheduled for elective TURP surgery under central neuraxial block,
      were studied. Their preoperative and post-operative serum sodium, potassium and
      calcium levels were measured. When duration of surgery exceeds 60 min, serum
      sodium and potassium levels were done intra-operatively with venous blood samples
      by using blood gas analyser. The height of irrigation fluid column was kept
      constant at 60 cm. These changes were correlated with the volume of irrigating
      fluid used, duration of procedure and the volume of prostate gland resected.
      STATISTICAL ANALYSIS USED: The values of pre and postoperative sodium, potassium
      and calcium serum levels were compared and statistical significance of the
      difference in values was assessed using Student's paired t test. RESULTS:
      Statistically significant reduction of serum sodium levels (hyponatremia) and
      elevation of serum potassium levels (hyperkalemia) were observed post
      operatively, which was directly proportional to volume of irrigating fluid used,
      duration of procedure and volume of prostate gland resected. No significant
      changes in serum calcium level were observed. CONCLUSIONS: To measure serum
      electrolytes changes during TURP surgery, it is simple and economical method for
      indirect assessment of fluid absorption for early identification of TURP
      syndrome.

PMID- 21189850
TI  - Combined use of remifentanil and propofol to limit patient movement during
      retinal detachment surgery under local anesthesia.
AB  - BACKGROUND: One of the drawbacks of performing ophthalmic surgery under local
      anesthesia is patient movement, which might affect optimal surgical outcome.
      PURPOSE: The study aims to evaluate the efficacy of the combined use of propofol
      and remifentanil as a sedative technique in comparison with the use of propofol
      alone to limit patient discomfort and movement during local anesthesia for vitreo
      retinal surgery lasting for more than two hours. MATERIALS AND METHODS: A total
      of 140 patients scheduled for vitreo-retinal surgery under local anesthesia, with
      an expected surgical time of more than two hours, were included in the study.
      Patients were divided randomly into two equal groups: group I where patients were
      given propofol and remifentanil by continuous infusion and group II where
      patients were given propofol alone by continuous infusion. RESULTS: The two
      groups were comparable with regard to age, weight, gender, ASA physical status
      and duration of surgery. There was a significant decrease in heart rate and mean
      arterial blood pressure (MABP) in each group 10 minutes after the start of
      sedation compared with pre-sedation data and continued all through the procedure.
      There was an insignificant difference between the two groups with regard to
      changes in heart rate and MABP all through surgical procedure. There was no
      significant difference between the two groups with regard to the incidence of
      complications except for an increased incidence of breakthrough pain and
      discomfort which necessitated the use of fentanyl as a rescue treatment in the
      propofol group P<0.001. There were no instances of movements with a major effect
      on the surgical field, which could have affected surgical outcome, in the two
      groups. The number of patients who did not move was significantly higher, 56
      (80%), in group I compared with 38 (54.29%) in group II with P<0.001. The
      ophthalmologist satisfaction scale was significantly higher in group I (4.5+/
      0.63) compared with group II (3.7+/-1.04) with P=0.0016. CONCLUSION: The combined
      use of propofol and remifentanil as a continuous infusion before performance of
      the block and during lengthy vitreo-retinal surgery was associated with a lower
      incidence of patient discomfort, breakthrough pain, and patient movement along
      with high degree of surgeons' satisfaction and hemodynamic stability.

PMID- 21189851
TI  - Cisatracurium in different doses versus atracurium during general anesthesia for
      abdominal surgery.
AB  - BACKGROUND: Cisatracurium in clinical practice is devoid of histamine-induced
      cardiovascular effects. On the other hand, 2 ED(95) doses of cisatracurium (100 u
      g/kg) do not create satisfactory intubating conditions such as those seen with
      equipotent doses of atracurium. The recommended intubating dose of cisatracurium
      is 3 ED(95). To understand this discrepancy better, we evaluated the potency and
      onset of atracurium and cisatracurium. MATERIALS AND METHODS: The study designed
      as randomized controlled clinical trial to compare between atracurium (2*ED(95))
      and different doses of cisatracurium (2*ED(95), 4*ED(95), 6*ED(95)) regarding
      onset time, duration of action, condition of intubation, hemodynamic effects, and
      sings of histamine release clinically. Sixty four patients were randomly assigned
      to one of four groups, the first group (group 1) received 2*ED(95) dose of
      atracurium, group 2 received 2*ED(95) dose of cisatracurium, group 3 received
      4*ED(95) dose of cisatracurium, while group 4 received 6*ED(95) dose of
      cisatracurium. The Datex relaxograph (Type NMT-100-23-01, S/N: 37541) for
      neuromuscular monitoring was used. RESULTS: HR, MABP was statistically
      significant increased post-intubation with administration of 2*ED(95) dose of
      atracurium in group 1 and the same dose of cisatracurium in group 2 but 5-20 min
      later was not statistically significant with administration of 4*ED(95) and
      6*ED(95) doses of cisatracurium in groups 3 and 4, respectively. Onset time was
      found to be significantly lower with 2*ED(95) dose of atracurium than with the
      same dose of cisatracurium. At the same time, higher doses of cisatracurium
      (4*ED(95) and 6*ED(95)) showed onset time and longer duration of action that was
      significantly lower than with atracurium and with lower dose of cisatracurium
      (2*ED(95)). Only 6*ED(95) dose of cisatracurium showed statistically significant
      difference versus the atracurium dose with higher percentages of patients with
      excellent condition of intubation. 4*ED(95) and 6*ED(95) doses of cisatracurium
      were significantly better than 2*ED(95) dose of cisatracurium. 2*ED(95) dose of
      atracurium and 2*ED(95) dose of cisatracurium were similar, while 4*ED(95) and
      6*ED(95) doses of cisatracurium were significantly better than atracurium and
      2*ED(95) dose of cisatracurium. CONCLUSION: The same dose (2*ED(95) dose)
      atracurium is more effective neuromuscular blocking agent than cisatracurium,
      while higher doses of cisatracurium 4*ED(95) and 6*ED(95) provide more effective,
      more rapid neuromuscular blocking with longer duration of action, stable
      hemodynamic status, and no associated signs of histamine release clinically.

PMID- 21189852
TI  - Assessment of difficult laryngoscopy by electronically measured maxillo
      pharyngeal angle on lateral cervical radiograph: A prospective study.
AB  - BACKGROUND: Difficult airway continued to be a major cause of anesthesia-related
      morbidity and mortality. Successful airway management depends on direct
      laryngoscopy and tracheal intubation. Difficult laryngoscopy is a resultant of
      incomplete structural arrangements during the process of head positioning.
      Through clinical history, examination of the patients along with craniofacial
      indices alerts the anesthetist for difficult laryngoscopy. But it does not
      predict all causes of difficult laryngoscopy during pre-anesthetic evaluation.
      The maxillo-pharyngeal angle, an upper airway anatomical balance, was proposed
      for better understanding the pathophysiology of difficult laryngoscopy. In our
      study we have assess difficult laryngoscopy by electronically measuring maxillo
      pharyngeal angles on a lateral cervical radiograph. This angle is normally
      greater than 100 degrees . Less than 90 degrees  angle suggests either impossible
      or difficult direct laryngoscopy when all known craniofacial indices were within
      the normal range. Cervical radiographic assessment is a simple, economical, and
      non-invasive predictive method for difficult laryngoscopy. It should be used
      routinely along with other indices as pre-anesthetic airway assessment criteria
      to predict the difficult laryngoscopy. CONTEXT: Difficulties with airway
      management continue to be a major cause of anesthesia-related morbidity,
      mortality, and litigation. Pre-operative assessment of difficult laryngoscopy by
      the simple and non-invasive radiological method can help to prevent them. AIMS:
      To assess the difficult laryngoscopy pre operatively by a simple and non invasive
      radiological method by electronically measuring maxillo-pharyngeal angle on a
      lateral cervical radiograph and it's correlation with Cormack and Lehane grading.
      SETTINGS AND DESIGN: This is a controlled, nonrandomized, prospective, cohort
      observation study. PATIENTS AND METHODS: The 157 adult consented patients of ASA
      grade I to III of either sex, scheduled for elective surgery under general
      anesthesia with endo-tracheal intubation, were studied. The patients with
      identified difficult airway indices were excluded from the study. The maxillo
      pharyngeal angle was electronically measured on a lateral cervical radiograph and
      was correlated with ease or difficulty of laryngoscopy under general anesthesia.
      Their degree of laryngeal exposure according to Cormack and Lehane classification
      grade was also noted. STATISTICAL ANALYSIS USED: We performed univariate analyses
      to evaluate the association between the covariates and direct laryngoscopy.
      RESULTS: In 148 patients (94.28%), the maxillo-pharyngeal angle was more than 100
      degrees , in 7 patients (4.45%) it was less than 90 degrees , and in 2 patients
      (1.27%) the M-P angle was less than 85 degrees  with normal craniofacial indices.
      When the MP angle was less than 90 degrees , the direct laryngoscopy was
      difficult which could be compared with to Cormack and Lehane classification grade
      III and IV. CONCLUSIONS: Lateral cervical radiographic assessment should be used
      as pre-anesthetic airway assessment criteria to predict the difficult
      laryngoscopy as it is a simple, safe and non-invasive method.

PMID- 21189853
TI  - Comparison of esmolol and labetalol, in low doses, for attenuation of
      sympathomimetic response to laryngoscopy and intubation.
AB  - OBJECTIVE: The present study compared the efficacy of esmolol and labetalol, in
      low doses, for attenuation of sympathomimetic response to laryngoscopy and
      intubation. DESIGN: Prospective, randomized, placebo controlled, double-blinded
      study. SETTING: Operation room. PATIENTS AND METHODS: 75 ASA physical status I
      and II adult patients, aged 18-45 years undergoing elective surgical procedures,
      requiring general anesthesia and orotracheal intubation. INTERVENTIONS: Patients
      were allocated to any of the three groups (25 each)-Group C (control)10 ml 0.9%
      saline i.v. Group E (esmolol) 0.5 mg/kg diluted with 0.9% saline to 10 ml i.v.
      Group L (labetalol) 0.25 mg/kg diluted with 0.9% saline to 10 ml i.v. In the
      control group 10 ml of 0.9% saline was given both at 2 and 5 min prior to
      intubation. In the esmolol group 0.5 mg/kg of esmolol (diluted with 0.9% saline
      to 10 ml) was given 2 min prior and 10 ml of 0.9% saline 5 min prior to
      intubation. In the labetalol group 10 ml of 0.9% saline was administered 2 min
      prior and 0.25 mg/kg of labetalol (diluted with 0.9% saline to 10 ml) 5 min prior
      to intubation. All the patients were subjected to the same standard anesthetic
      technique. MEASUREMENTS: Heart rate (HR), systolic blood pressure (SBP) and
      diastolic blood pressure (DBP) were recorded prior to induction, at time of
      intubation and 1, 3, 5, and 10 min after intubation. Mean arterial pressure (MAP)
      and rate pressure product (RPP) were calculated. Abnormal ECG changes were also
      recorded. RESULTS: Compared to placebo and esmolol (0.5 mg/kg), labetalol (0.25
      mg/kg) significantly attenuated the rise in heart rate, systolic blood pressure,
      and RPP during laryngoscopy and intubation. However, the difference was not
      statistically significant among the values for DBP and MAP. CONCLUSION: In lower
      doses, labetalol (0.25 mg/kg) is a better agent than esmolol (0.5 mg/kg) in
      attenuating the sympathomimetic response to laryngoscopy and intubation.

PMID- 21189854
TI  - Assessment of role of perioperative melatonin in prevention and treatment of
      postoperative delirium after hip arthroplasty under spinal anesthesia in the
      elderly.
AB  - CONTEXT: Little is known about the relationship between sedative drugs used
      preoperatively and postoperative delirium. Melatonin is a drug used to sedate
      patients preoperatively and is hypothesized by recent works to have a curative
      effect on postoperative delirium. AIMS: The incidence of postoperative delirium
      will be tested if affected by three different sedative drugs including melatonin.
      SETTINGS AND DESIGN: Controlled randomized doubleblind study. PATIENTS AND
      METHODS: Three-hundred patients aged>65 years scheduled for hip arthroplasty
      under spinal anesthesia were randomly distributed to one of the four groups.
      Group 1 (control) received nothing for sedation. Group 2 (melatonin) received 5
      mg melatonin. Group 3 (midazolam) received 7.5 mg midazolam. Group 4 (clonidine)
      received 100 MUg clonidine. These medications were given orally at sleep time at
      night of operation and another dose 90 min before operative time. Patients who
      developed postoperative delirium received 5 mg of melatonin 9 pm for three
      successive days in a trial to treat delirium. STATISTICAL ANALYSIS USED:
      Statistical analysis was done using the SPSS Software (version 13). RESULTS:
      Total of 222 patients completed the study. Percentage of postoperative delirium
      in the control group was 32.65% (16/49 patients). The melatonin group showed a
      statistically significant decrease in the percentage of postoperative delirium to
      9.43% (5/53 patients). Melatonin was successful in treating 58.06% of patients
      suffered postoperative delirium (36/62 patients) with no difference between
      different groups. CONCLUSIONS: Postoperative delirium is affected with the drug
      used for preoperative sedation. Melatonin was successful in decreasing
      postoperative delirium when used preoperatively and in treating more than half of
      patients developed postoperative delirium when used for three postoperative
      nights.

PMID- 21189855
TI  - Superficial extraconal blockade for vitreoretinal surgery.
AB  - CONTEXT: Needle length plays an important role for the success of ophthalmic
      block. The standard practice is to use 25 mm needles length; however,
      unnecessarily long needles may increase the risk of complications especially in
      the presence of staphyloma or previous scleral buckle. AIMS: This work was
      designed to compare the efficacy of using 15 and 25 mm needle in performing
      extraconal block for patients undergoing vitreoretinal surgery. SETTINGS AND
      DESIGN: Prospective randomized double blinded study. MATERIALS AND METHODS: A
      total of 120 patients were enrolled in this study and were divided in two groups.
      In group (1) extraconal block was performed using 25 mm needle, while in group
      (2) 15 mm needle was used. After primary injection, assessment of the block was
      done by an anesthesiologist who was unaware of the needle used. If satisfactory
      akinesia was not achieved a supplementation was provided. At the end of the
      procedures, patients and surgeons were asked to assess their pain and
      satisfaction with the anesthetic technique. STATISTICAL ANALYSIS USED: The sample
      size calculation using N-Quary version 4. Numerical and categorical data were
      analyzed using an independent sample, a two-tailed t-test, and chi-square test,
      respectively. RESULTS: The volume of primary injectable was significantly higher
      in group 2. The two groups were comparable as regards total volume of local
      anesthetic, supplementation rate, akinesia, pain score, and surgeon satisfaction.
      CONCLUSIONS: Using 15 mm needle length to perform extraconal blockade for
      posterior segment procedures is equally effective to 25 mm needle.

PMID- 21189856
TI  - Comparison of efficacy of bupivacaine and fentanyl with bupivacaine and
      sufentanil for epidural labor analgesia.
AB  - OBJECTIVES: A study to compare the efficacy between fentanyl and sufentanil
      combined with low concentration (0.0625%) of bupivacaine for epidural labor
      analgesia in laboring women MATERIALS AND METHODS: Fifty full term parturients
      received an initial bolus dose of a 10 ml solution containing 0.125% bupivacaine.
      The patients were randomly divided into two: group F received 0.0625% bupivacaine
      with 2.5 mcg/ml fentanyl and group S received 0.0625% bupivacaine with 0.25
      mcg/ml sufentanil. Verbal analogue pain scores, need of supplementary/rescue
      boluses dose of bupivacaine consumed, mode of delivery, maternal satisfaction,
      and neonatal Apgar scores were recorded. No significant difference was observed
      between both groups. RESULTS: Both the groups provided equivalent labor analgesia
      and maternal satisfaction. The chances of cesarean delivery were also not
      increased in any group. No difference in the cephalad extent of sensory
      analgesia, motor block or neonatal Apgar score were observed. Although mean pain
      scores throughout the labor and delivery were similar in both groups, more
      patients in fentanyl group required supplementary boluses though not
      statistically significant. CONCLUSION: We conclude that both 0.0625% bupivacaine
      fentanyl (2.5 MUg/ml) and 0.0625% bupivacaine-sufentanil (0.25 MUg/ml) were
      equally effective by continuous epidural infusion in providing labor analgesia
      with hemodynamic stability achieving equivalent maternal satisfaction without
      serious maternal or fetal side effects. We found that sufentanil was 10 times
      more potent than fentanyl as an analgesic for continuous epidural labor
      analgesia.

PMID- 21189857
TI  - Awareness among resident doctors with regards to cardiac defibrillators.
AB  - BACKGROUND AND AIMS: Electrical defibrillation is the most important therapy for
      patients in cardiac arrest. The audit was aimed to assess awareness among
      residents with respect to routine preuse checking of cardiac defibrillators.
      MATERIALS AND METHODS: The audit was conducted at a multispeciality tertiary care
      referral and teaching center by means of a printed questionnaire from
      anaesthesiology residents. A database was prepared and responses were analyzed.
      RESULTS: Eighty resident doctors participated in the audit. Most (97.8%) of the
      residents were sure of the presence of a defibrillator in the operation room
      (OR); 70% of postgraduates (PG)s were aware of the location of the defibrillator
      in the OR as compared to 83.7% of the senior resident (SRs). Also, 32.1%
      residents routinely check the availability of a defibrillator. The working
      condition of the defibrillator was checked by 21.7% of the residents; 25.3%
      ensured delivery of the set charge. Further, 8.2% of residents ensured
      availability of both adult and paediatric paddles. About 27.8% of residents
      ensured the availability of appropriate conducting gel and 53.8% residents were
      of the opinion that the responsibility of checking the functioning and
      maintenance of the defibrillators lies with themselves. Some 22% thought that
      both doctors and technical staff should share the responsibility, while 19.5%
      opined that it should be the responsibility of the technical staff. CONCLUSION:
      All medical equipment is to be tested prior to initial use and periodically
      thereafter. An extensive, recurring training program, and continued attention to
      the training of clinical personnel is required to ensure that they are proficient
      in the operation and testing of specific defibrillator models in their work area.
      We conclude that apart from awareness of the use of the equipment we are using,
      its preuse testing is must. All resident doctors should be aware of the presence
      and adequate functioning of the defibrillator in their ORs and this audit
      reinforces the need for training of all resident doctors.

PMID- 21189859
TI  - Perioperative care of a child with non-ketotic hyperglycinemia.
AB  - Non-ketotic hyperglycinemia (NKGH) is an autosomal recessive disorder of glycine
      metabolism. Defective glycine cleavage results in elevated concentrations of
      glycine in plasma, urine and cerebrospinal fluid. The accumulation of glycine, an
      inhibitory neurotransmitter, leads to a clinical presentation of apnea, lethargy,
      hypotonia, seizures, and severe psychomotor retardation. There are four clinical
      variants of NKHG, which have been described in the medical literature. Neonatal
      NKHG is the most common as well as the most devastating and lethal form of the
      disorder. Given the multi-system involvement of the disorder, there are several
      perioperative concerns of such patients with delayed emergence requiring
      supported ventilation being a common postoperative outcome for NKHG patients. We
      report the perioperative management of a 4-year-old boy with NKGH who required
      anesthetic care during an adenoidectomy and tonsillectomy for obstructive sleep
      apnea.

PMID- 21189858
TI  - Perioperative care following complex laryngotracheal reconstruction in infants
      and children.
AB  - Laryngotracheal reconstruction (LTR) involves surgical correction of a stenotic
      airway with cartilage interpositional grafting, followed by either placement of a
      tracheostomy and an intraluminal stent (two-stage LTR) or placement of an
      endotracheal tube with postoperative sedation and mechanical ventilation for an
      extended period of time (singlestage LTR). With single-stage repair, there may be
      several perioperative challenges including the provision of adequate sedation,
      avoidance of the development of tolerance to sedative and analgesia agents, the
      need to use neuromuscular blocking agents, the maintenance of adequate pulmonary
      toilet to avoid perioperative nosocomial infections, and optimization of
      postoperative respiratory function to facilitate successful tracheal extubation.
      We review the perioperative management of these patients, discuss the challenges
      during the postoperative period, and propose recommendations for the prevention
      of reversible causes of extubation failure in this article. Optimization to
      ensure a timely tracheal extubation and successful weaning of mechanical
      ventilator, remains the primary key to success in these surgeries as extubation
      failure or the need for prolonged postoperative mechanical ventilation can lead
      to failure of the graft site, the need for prolonged Pediatric Intensive Care
      Unit care, and in some cases, the need for a tracheostomy to maintain an adequate
      airway.

PMID- 21189860
TI  - General anesthesia for repair of omphalocele in a pair of conjoined twins in
      Enugu, Nigeria.
AB  - Conjoined twins have been viewed with fascination since antiquity. There are
      numerous reports in the literature documenting anesthetic management strategies
      for the separation of conjoined twins. There are also reports in the literature
      detailing anesthetic approaches for surgical procedures not involving separation.
      This is the first report of the anesthetic management of a set of omphalagous
      presenting for palliative repair of omphalocele in Nigeria.

PMID- 21189861
TI  - Masseter muscle rigidity: Atypical malignant hyperthermia presentation or
      isolated event?
AB  - This report describes a case of masseter muscle rigidity encountered at the start
      of an elective gynaecological procedure. At preoperative assessment, the patient,
      a 41-year old woman with a previous non-eventful surgical and anesthetic history
      was given a Mallampati score of 3. Following suxamethonium administration, full
      mouth opening proved difficult. Laryngoscopy and tracheal intubation were not
      possible leading to the eventual use of a laryngeal mask airway and resulting in
      a successful anaesthetic outcome. A number of possibilities that may account for
      this situation as well as viable options for airway access in such cases are
      discussed below.

PMID- 21189862
TI  - My patient is allergic to eggs, can i use propofol? A case report and review.
AB  - Rather than other drugs, propofol is more likely to be used for induction of
      anesthesia to cause an allergic reaction. Propofol is becoming the most common
      intravenous agent used for induction as well as maintenance of anaesthesia.
      Allergy to propofol is rarely reported. We present a case of 4-year-old boy
      presented for elective adenotonsillectomy with past medical history of eczema and
      multiple allergies to food. He developed what seems to be an allergic reaction to
      propofol. We concluded that anaesthetists should be alerted when using propofol
      in patients with history of atopy or several drug allergies. Current evidence
      suggests that egg allergic patients are not more likely to develop anaphylaxis
      when exposed to propofol. If reactions to drugs occurred, it is always advisable
      to ascertain the exact allergen in each individual case before deciding
      causality. Serum tryptase, skin prick, intradermal testing, or serologic testing
      should be done to confirm the diagnosis of an anaphylactic reaction.

PMID- 21189863
TI  - Laryngoscope based lighted stylet for intubation: An innovation.

PMID- 21189864
TI  - Damaged guidewire by the introducer needle tip while inserting central venous
      catheter in subclavian vein by supraclavicular approach.

PMID- 21189866
TI  - Nrf2 target genes are induced under marginal selenium-deficiency.
AB  - A suboptimal selenium supply appears to prevail in Europe. The current study,
      therefore, was focused on the changes in gene expression under a suboptimal
      selenium intake. Previous microarray analyses in the colon of mice fed either a
      selenium-adequate or a moderately deficient diet revealed a change in genes of
      several pathways. Severe selenium-deficiency has been found previously to
      influence Nrf2-regulated genes of the adaptive response. Since the previous
      pathway analyses were done with a program not searching for Nrf2 target genes,
      respective genes were manually selected and confirmed by qPCR. qPCR revealed an
      induction of phase II (Nqo1, Gsts, Sult1b1 and Ugt1a6) and antioxidant enzymes
      (Hmox1, Mt2, Prdx1, Srxn1, Sod1 and Gclc) under the selenium-poor diet, which is
      considered to compensate for the loss of selenoproteins. The strongest effects
      were observed in the duodenum where preferentially genes for antioxidant enzymes
      were up-regulated. These also include the mRNA of the selenoproteins TrxR1 and
      GPx2 that would enable their immediate translation upon selenium refeeding. The
      down-regulation of Gsk3beta in moderate selenium-deficiency observed in the
      previous paper provides a possible explanation for the activation of the Nrf2
      pathway, because inhibition of GSK3beta results in the nuclear accumulation of
      Nrf2.

PMID- 21189865
TI  - The Micronutrient Genomics Project: a community-driven knowledge base for
      micronutrient research.
AB  - Micronutrients influence multiple metabolic pathways including oxidative and
      inflammatory processes. Optimum micronutrient supply is important for the
      maintenance of homeostasis in metabolism and, ultimately, for maintaining good
      health. With advances in systems biology and genomics technologies, it is
      becoming feasible to assess the activity of single and multiple micronutrients in
      their complete biological context. Existing research collects fragments of
      information, which are not stored systematically and are thus not optimally
      disseminated. The Micronutrient Genomics Project (MGP) was established as a
      community-driven project to facilitate the development of systematic capture,
      storage, management, analyses, and dissemination of data and knowledge generated
      by biological studies focused on micronutrient-genome interactions. Specifically,
      the MGP creates a public portal and open-source bioinformatics toolbox for all
      "omics" information and evaluation of micronutrient and health studies. The core
      of the project focuses on access to, and visualization of, genetic/genomic,
      transcriptomic, proteomic and metabolomic information related to micronutrients.
      For each micronutrient, an expert group is or will be established combining the
      various relevant areas (including genetics, nutrition, biochemistry, and
      epidemiology). Each expert group will (1) collect all available knowledge, (2)
      collaborate with bioinformatics teams towards constructing the pathways and
      biological networks, and (3) publish their findings on a regular basis. The
      project is coordinated in a transparent manner, regular meetings are organized
      and dissemination is arranged through tools, a toolbox web portal, a
      communications website and dedicated publications.

PMID- 21189867
TI  - Gene expression profiles in human peripheral blood mononuclear cells as
      biomarkers for nutritional in vitro and in vivo investigations.
AB  - Identification of chemopreventive substances may be achieved by measuring
      biological endpoints in human cells in vitro. Since generally only tumour cells
      are available for such investigations, our aim was to test the applicability of
      peripheral blood mononuclear cells (PBMC) as an in vitro primary cell model since
      they mimic the human in vivo situation and are relatively easily available. Cell
      culture conditions were refined, and the basal variation of gene expression
      related to drug metabolism and stress response was determined. Results were
      compared with profiles of an established human colon cell line (HT29) as
      standard. For biomarker development of nutritional effects, PBMC and HT29 cells
      were treated with potentially chemopreventive substances (chrysin and butyrate),
      and gene expression was determined. Key results were that relevant stress
      response genes, such as glutathione S-transferase T2 (GSTT2) and GSTM2, were
      modulated by butyrate in PBMC as in HT29 cells, but the blood cells were less
      sensitive and responded with high individual differences. We conclude that these
      cells may serve as a surrogate tissue in dietary investigations and the
      identified differentially expressed genes have the potential to become marker
      genes for population studies on biological effects.

PMID- 21189868
TI  - The effects of betaine treatment on rats fed an acute bolus of ethanol at 3 and
      12 h post bolus: a microarray analysis.
AB  - Betaine, a methyl donor active in methionine metabolism, is effective in
      preventing and reversing experimental alcohol liver disease. The metabolic and
      molecular biologic mechanisms involved in this prevention are only partially
      known. To further investigate how betaine modifies the effects of ethanol on the
      liver, rats were given an acute ethanol bolus with or without betaine and the
      results were compared to isocaloric dextrose-fed controls. Livers were subjected
      to microarray analysis, and functional pathways and individual gene expression
      changes were analyzed. Experimental groups were compared by Venn diagrams showing
      that both ethanol and betaine caused a change in the expression of a large number
      of genes indicating that the changes were global. The bio-informatic analysis
      showed that all the KEGG functional pathways were affected and mainly down
      regulated at 3 h post bolus when ethanol plus betaine were compared with ethanol
      fed rats. The most profound effect of betaine was on the metabolic pathways both
      at 3 and 12 h post bolus. At 3 h, the changes in gene expression were mostly down
      regulated, but at 12 h, the changes were regulated equally up and down. This
      hypothesis-driven analysis showed that the effects of betaine on the effects of
      ethanol were partly transient.

PMID- 21189869
TI  - Gene expression profiles in human HepG2 cells treated with extracts of the
      Tamarindus indica fruit pulp.
AB  - Tamarindus indicaL. (T. indica) or locally known as asam jawa belongs to the
      family of Leguminosae. The fruit pulp had been reported to have antioxidant
      activities and possess hypolipidaemic effects. In this study, we attempted to
      investigate the gene expression patterns in human hepatoma HepG2 cell line in
      response to treatment with low concentration of the fruit pulp extracts.
      Microarray analysis using Affymetrix Human Genome 1.0 S.T arrays was used in the
      study. Microarray data were validated using semi-quantitative RT-PCR and real
      time RT-PCR. Amongst the significantly up-regulated genes were those that code
      for the metallothioneins (MT1M, MT1F, MT1X) and glutathione S-transferases
      (GSTA1, GSTA2, GST02) that are involved in stress response. APOA4, APOA5, ABCG5
      and MTTP genes were also significantly regulated that could be linked to
      hypolipidaemic activities of the T. indica fruit pulp.

PMID- 21189871
TI  - Are we using right dose of oxytocin?

PMID- 21189870
TI  - Nutrigenomic analysis of the protective effects of bilberry anthocyanin-rich
      extract in apo E-deficient mice.
AB  - Intake of anthocyanin-rich foods has been associated with a reduced risk of
      cardiovascular diseases. Supplementation with anthocyanin-rich extracts from
      black rice or purple sweet potato was reported to attenuate atherosclerotic
      lesion development in apolipoprotein E-deficient (apo E(-/-)) mice. However, the
      mechanism(s) of their preventive action are not completely understood. Previous
      studies revealed that anthocyanins altered mRNA levels of genes related to
      atherosclerosis in cultured macrophages and endothelial cells, but in vivo
      studies remain scarce. The aim of the study was to investigate the impact of
      bilberry anthocyanin-rich extract (BE) supplementation on gene expression in the
      liver of apo E(-/-) mice, the widely used model of atherosclerosis. The liver was
      chosen because it is the main site of lipid metabolism. Apo E(-/-) mice received
      for 2 weeks a standard diet supplemented with a nutritional dose of BE (0.02%).
      This study focused on the early stage of atherosclerosis development for better
      assessment of anthocyanin action on initiation mechanisms of this pathology. The
      results showed that a 2-week supplementation significantly reduced plasmatic
      total cholesterol and hepatic triglyceride levels, whereas the plasmatic
      antioxidant status remained unchanged. Transcriptional analysis, using
      microarrays, revealed that the expression of 2,289 genes was significantly
      altered. BE over-expressed genes involved in bile acid synthesis and cholesterol
      uptake into the liver and down-regulated the expression of pro-inflammatory
      genes. These results suggest an anti-atherogenic effect of BE through the
      regulation of cholesterol metabolism and liver inflammation and provide a global
      integrated view of the mechanisms involved in the preventive action of this
      extract. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article
      (doi:10.1007/s12263-010-0171-0) contains supplementary material, which is
      available to authorized users.

PMID- 21189872
TI  - Perioperative fasting: A time to relook.

PMID- 21189873
TI  - Obstetric anaesthesia: Widening horizons?

PMID- 21189874
TI  - Anaemia and pregnancy: Anaesthetic implications.
AB  - Anaemia in pregnancy defined as haemoglobin (Hb) level of < 10 gm/dL, is a
      qualitative or quantitative deficiency of Hb or red blood cells in circulation
      resulting in reduced oxygen (O2)- carrying capacity of the blood. Compensatory
      mechanisms in the form of increase in cardiac output (CO), PaO(2), 2,3
      diphosphoglycerate levels, rightward shift in the oxygen dissociation curve
      (ODC), decrease in blood viscosity and release of renal erythropoietin, get
      activated to variable degrees to maintain tissue oxygenation and offset the
      decreases in arterial O(2) content. Parturients with concomitant medical diseases
      or those with acute ongoing blood losses may get decompensated, leading to
      serious consequences like right heart failure, angina or tissue hypoxemia in
      severe anaemia. Preoperative evaluation is aimed at assessing the severity and
      cause of anaemia. The concept of an acceptable Hb level varies with the
      underlying medical condition, extent of physiological compensation, the threat of
      bleeding and ongoing blood losses. The main anaesthetic considerations are to
      minimize factors interfering with O(2) delivery, prevent any increase in oxygen
      consumption and to optimize the partial pressure of O(2) in the arterial blood.
      Both general anaesthesia and regional anaesthesia can be employed judiciously.
      Monitoring should focus mainly on the adequacy of perfusion and oxygenation of
      vital organs. Hypoxia, hyperventilation, hypothermia, acidosis and other
      conditions that shift the ODC to left should be avoided. Any decrease in CO
      should be averted and aggressively treated.

PMID- 21189875
TI  - Diabetic parturient - Anaesthetic implications.
AB  - Pregnancy induces progressive changes in maternal carbohydrate metabolism. As
      pregnancy advances insulin resistance and diabetogenic stress due to placental
      hormones necessitate compensatory increase in insulin secretion. When this
      compensation is inadequate gestational diabetes develops. 'Gestational diabetes
      mellitus' (GDM) is defined as carbohydrate intolerance with onset or recognition
      during pregnancy. Women diagnosed to have GDM are at increased risk of future
      diabetes predominantly type 2 DM as are their children. Thus GDM offers an
      important opportunity for the development, testing and implementation of clinical
      strategies for diabetes prevention. Timely action taken now in screening all
      pregnant women for glucose intolerance, achieving euglycaemia in them and
      ensuring adequate nutrition may prevent in all probability, the vicious cycle of
      transmitting glucose intolerance from one generation to another. Given that
      diabetic mothers have proportionately larger babies it is likely that vaginal
      delivery will be more difficult than in the normal population, with a higher rate
      of instrumentally assisted delivery, episiotomy and conversion to urgent
      caesarean section. So an indwelling epidural catheter is a better choice for
      labour analgesia as well to use, should a caesarean delivery become necessary.
      Diabetes in pregnancy has potential serious adverse effects for both the mother
      and the neonate. Standardized multidisciplinary care including anaesthetists
      should be carried out obsessively throughout pregnancy. Diabetes is the most
      common endocrine disorder of pregnancy. In pregnancy, it has considerable cost
      and care demands and is associated with increased risks to the health of the
      mother and the outcome of the pregnancy. However, with careful and appropriate
      screening, multidisciplinary management and a motivated patient these risks can
      be minimized.

PMID- 21189876
TI  - Management of foetal asphyxia by intrauterine foetal resuscitation.
AB  - Management of foetal distress is a subject of gynaecological interest, but an
      anaesthesiologist should know about resuscitation, because he should be able to
      treat the patient, whenever he is directly involved in managing the parturient
      patient during labour analgesia and before an emergency operative delivery.
      Progressive asphyxia is known as foetal distress; the foetus does not breathe
      directly from the atmosphere, but depends on maternal circulation for its oxygen
      requirement. The oxygen delivery to the foetus depends on the placental (maternal
      side), placental transfer and foetal circulation. Oxygen transport to the foetus
      is reduced physiologically during uterine contractions in labour. Significant
      impairment of oxygen transport to the foetus, either temporary or permanent may
      cause foetal distress, resulting in progressive hypoxia and acidosis.
      Intrauterine foetal resuscitation comprises of applying measures to a mother in
      active labour, with the intention of improving oxygen delivery to the distressed
      foetus to the base line, if the placenta is functioning normally. These measures
      include left lateral recumbent position, high flow oxygen administration,
      tocolysis to reduce uterine contractions, rapid intravenous fluid administration,
      vasopressors for correction of maternal hypotension and amnioinfusion for
      improving uterine blood flow. Intrauterine Foetal Resuscitation measures are easy
      to perform and do not require extensive resources, but the results are
      encouraging in improving the foetal well-being. The anaesthesiologist plays a
      major role in the application of intrauterine foetal resuscitation measures.

PMID- 21189877
TI  - Labour analgesia: Recent advances.
AB  - Advances in the field of labour analgesia have tread a long journey from the days
      of ether and chloroform in 1847 to the present day practice of comprehensive
      programme of labour pain management using evidence-based medicine. Newer advances
      include introduction of newer techniques like combined spinal epidurals, low-dose
      epidurals facilitating ambulation, pharmacological advances like introduction of
      remifentanil for patient-controlled intravenous analgesia, introduction of newer
      local anaesthetics and adjuvants like ropivacaine, levobupivacaine, sufentanil,
      clonidine and neostigmine, use of inhalational agents like sevoflourane for
      patient-controlled inhalational analgesia using special vaporizers, all have
      revolutionized the practice of pain management in labouring parturients.
      Technological advances like use of ultrasound to localize epidural space in
      difficult cases minimizes failed epidurals and introduction of novel drug
      delivery modalities like patient-controlled epidural analgesia (PCEA) pumps and
      computer-integrated drug delivery pumps have improved the overall maternal
      satisfaction rate and have enabled us to customize a suitable analgesic regimen
      for each parturient. Recent randomized controlled trials and Cochrane studies
      have concluded that the association of epidurals with increased caesarean section
      and long-term backache remains only a myth. Studies have also shown that the
      newer, low-dose regimes do not have a statistically significant impact on the
      duration of labour and breast feeding and also that these reduce the instrumental
      delivery rates thus improving maternal and foetal safety. Advances in medical
      technology like use of ultrasound for localizing epidural space have helped the
      clinicians to minimize the failure rates, and many novel drug delivery modalities
      like PCEA and computer-integrated PCEA have contributed to the overall maternal
      satisfaction and safety.

PMID- 21189878
TI  - Anaesthesia for lower-segment caesarean section: Changing perspectives.
AB  - The number of caesarean sections has increased over the last two decades,
      especially in the developed countries. Hence, it has increasingly become a
      greater challenge to provide care for the parturient, but this has given
      obstetric anaesthetists a greater opportunity to contribute to obstetric
      services. While caesarean deliveries were historically performed using general
      anaesthesia, there is a recent significant move towards regional anaesthesia.
      Unique problems that patients with obesity and pre-eclampsia present will be
      discussed in the present article. New medications and devices now used in
      obstetric anaesthesia will change the practice and perspectives of our clinical
      practice.

PMID- 21189879
TI  - Complications of regional and general anaesthesia in obstetric practice.
AB  - Any anaesthetic technique, either regional or general, has potential for
      complications. Moreover, it has been seen that in obstetric patients, the
      complications are potentiated due to pregnancy-related changes in physiology and
      due to various other factors. Increasing trend of caesarean section in the
      setting of increasing maternal age, obesity and other concomitant diseases will
      continue to challenge the obstetric anaesthetist in his/her task of providing
      safe regional and general anaesthesia. This review has highlighted the possible
      complications of regional and general anaesthesia encountered during the
      obstetric anaesthesia practice.

PMID- 21189880
TI  - The critically ill obstetric patient - Recent concepts.
AB  - Obstetric patients admitted to an Intensive Care Unit (ICU) present a challenge
      to an intensivist because of normal physiological changes associated with
      pregnancy and puerperium, the specific medical diseases peculiar to pregnancy and
      the need to take care of both the mother and the foetus. Most common causes of
      admission to an ICU for obstetric patients are eclampsia, severe preeclampsia,
      haemorrhage, congenital and valvular heart disease, septic abortions, severe
      anemia, cardiomyopathy and non-obstetric sepsis. The purpose of this review is to
      present the recent concepts in critical care management of obstetric patients
      with special focus mainly on ventilatory strategies, treatment of shock and
      nutrition. The details regarding management of individual diseases would not be
      discussed as these would be beyond the purview of this article. In addition, some
      specific issues of importance while managing such patients would also be
      highlighted.

PMID- 21189881
TI  - Neonatal resuscitation: Current issues.
AB  - The following guidelines are intended for practitioners responsible for
      resuscitating neonates. They apply primarily to neonates undergoing transition
      from intrauterine to extrauterine life. The updated guidelines on Neonatal
      Resuscitation have assimilated the latest evidence in neonatal resuscitation.
      Important changes with regard to the old guidelines and recommendations for daily
      practice are provided. Current controversial issues concerning neonatal
      resuscitation are reviewed and argued in the context of the ILCOR 2005 consensus.

PMID- 21189882
TI  - Mitral stenosis and pregnancy: Current concepts in anaesthetic practice.
AB  - The incidence of rheumatic mitral stenosis is grossly reduced in India. Still,
      among heart disease complicating pregnancy, rheumatic mitral stenosis occupies a
      greater segment. The unique physiological changes in pregnancy and the
      pathological impact of mitral stenosis over pregnancy and labour are discussed in
      detail. A multidisciplinary approach in the diagnosis and management reduces the
      mortality and morbidity during peripartum. The labour analgesia technique and the
      evidence-based regional and general anaesthesia techniques are discussed at
      length in this article.

PMID- 21189883
TI  - "Nil per oral after midnight": Is it necessary for clear fluids?
AB  - Fasting before general anaesthesia aims to reduce the volume and acidity of
      stomach contents, thus reducing the risk of regurgitation and aspiration. Recent
      guidelines have recommended a shift in fasting policies from the standard 'nil
      per oral from midnight' to a more relaxed policy of clear fluid intake a few
      hours before surgery. The effect of preoperative oral administration of 150 ml of
      water 2 h prior to surgery was studied prospectively in 100 ASA I and II
      patients, for elective surgery. Patients were randomly assigned to two groups.
      Group I (n = 50) was fasting overnight while Group II (n = 50) was given 150 ml
      of water 2 h prior to surgery. A nasogastric tube was inserted after intubation
      and gastric aspirate was collected for volume and pH. The gastric fluid volume
      was found to be lesser in Group II (5.5 +/- 3.70 ml) than Group I (17.1 +/- 8.2
      ml) which was statistically significant. The mean pH values for both groups were
      similar. Hence, we conclude that patients not at risk for aspiration can be
      allowed to ingest 150 ml water 2 h prior to surgery.

PMID- 21189884
TI  - Effect of 6% hydroxyethyl starch-450 and low molecular weight dextran on blood
      sugar levels during surgery under subarachnoid block: A prospective randomised
      study.
AB  - Dextrans and hydroxyethyl starches produce significant levels of free glucose
      residues following metabolism. The following study was designed to compare 6%
      hydroxyethyl starch-450 with Dextran 40, both used as preloading fluids, for
      their potential to raise peri-operative blood glucose levels. After taking an
      informed consent, 180 non-diabetic adult patients, posted for elective surgery
      under spinal anaesthesia, were randomly divided into three groups, to receive
      Ringer's Lactate 20 ml/kg (group 1), Dextran 40,10 ml/kg (group 2) and Hestar 6%
      450, 10 ml/kg (group 3), over half an hour, prior to the subarachnoid block, as
      preloading fluid, and serial capillary blood glucose measurements were taken
      thereafter at regular intervals up to 240 minutes from the baseline reading. All
      the three preloading fluids, including Ringer's Lactate used as control, were
      seen to significantly increase the capillary blood glucose levels intra
      operatively (P < 0.05), but the rise with Dextran-40 was seen to be sustained and
      highly significant (P < 0.001). We thus conclude that, Dextran40 causes a
      sustained and significant rise in peri-operative blood glucose levels.

PMID- 21189885
TI  - Comparative analgesic efficacy of buprenorphine or clonidine with bupivacaine in
      the caesarean section.
AB  - The need for early ambulation for caring of the neonate by mothers makes
      postoperative pain management after cesarean delivery unique. Favorable results
      have been observed with buprenorphine, clonidine and bupivacaine as epidural
      analgesics. This prospective, randomised triple blind control study was carried
      out among 112 lower segment caesarean segment (LSCS) patients, divided into three
      groups, to assess the analgesic efficacy and side effects of epidural analgesia,
      with an intermittent top up of (i) bupivacaine (0.125%) and buprenorphine (0.075
      mg) (ii) bupivacaine (0.125%) and clonidine (37.5 microgram) and (iii)
      bupivacaine (0.125%) alone, in LSCS cases. The demographic characteristics (age,
      weight and height) of the three groups were comparable and the differences were
      not statistically significant. The mean duration of the analgesia was
      significantly longer in the group one patients receiving buprenorphine plus
      bupivacaine (690 +/- 35 minutes) and it was lowest in group three patients
      receiving bupivacaine (170 +/- 31 minutes) alone. The mean highest pain score
      (VAS scale) was significantly lower (3.4 +/- 0.6) in group one patients and it
      was highest in group three (6.7 +/- 0.8) patients. Requirement of continuation of
      epidural analgesia after 15 hours of operation and requirement of diclonfenac
      injections as well as incidence of itching and pruritus was significantly lower
      in group one patients. Incidence of nausea and vomiting was the lowest in group
      one patients. Incidence of respiratory depression, sedation and hypotension were
      nil in all three group of patients. Epidural buprenorphine combined with
      bupivacaine produced significantly longer duration and better quality of
      analgesia than bupivacaine combined with clonidine or bupivacaine alone, and it
      was safe in LSCS patients, for post-operative analgesia.

PMID- 21189886
TI  - Efficacy of clonidine as an adjuvant to bupivacaine for caudal analgesia in
      children undergoing sub-umbilical surgery.
AB  - Caudal epidural analgesia with bupivacaine is very popular in paediatric
      anaesthesia for providing intra- and postoperative analgesia. Several adjuvants
      have been used to prolong the action of bupivacaine. We evaluated the efficacy of
      clonidine added to bupivacaine in prolonging the analgesia produced by caudal
      bupivacaine in children undergoing sub-umbilical surgery. One hundred children,
      age one to three years, undergoing sub-umbilical surgery, were prospectively
      randomized to one of two groups: caudal analgesia with 1 ml/kg of 0.25%
      bupivacaine in normal saline (Group A) or caudal analgesia with 1 ml/kg of 0.25%
      bupivacaine with 1 ug/kg of clonidine in normal saline (Group B). Post-operative
      pain was assessed for 24 hours using the FLACC scale. The mean duration of
      analgesia was significantly longer in Group B (593.4 +/- 423.3 min) than in Group
      A (288.7 +/- 259.1 min); P < 0.05. The pain score assessed using FLACC scale was
      compared between the two groups, and children in Group B had lower pain scores,
      which was statistically significant. The requirement of rescue medicine was
      lesser in Group B. Clonidine in a dose of 1 ug/kg added to 0.25% bupivacaine for
      caudal analgesia, during sub-umbilical surgeries, prolongs the duration of
      analgesia of bupivacaine, without any side effects.

PMID- 21189887
TI  - A late presenting congenital diaphragmatic hernia misdiagnosed as spontaneous
      pneumothorax.
AB  - Congenital diaphragmatic hernia (CDH) is described as (1) failure of
      diaphragmatic closure at development, (2) presence of herniated abdominal
      contents into chest and (3) pulmonary hypoplasia. Usually, pleural space is
      drained urgently when there is respiratory distress and radiological appearance
      of mediastinal shift. We present a case of a 5-month-old baby, diagnosed as
      tension pneumothorax and treated with chest drain insertion. CDH was the
      intraoperative diagnosis.

PMID- 21189888
TI  - An unanticipated cardiac arrest and unusual post-resuscitation psycho-behavioural
      phenomena/near death experience in a patient with pregnancy induced hypertension
      and twin pregnancy undergoing elective lower segment caesarean section.
AB  - A case report of a primigravida, who was admitted with severe pregnancy induced
      hypertension (BP 160/122 mmHg) and twin pregnancy, is presented here.
      Antihypertensive therapy was initiated. Elective LSCS under general anaesthesia
      was planned. After the birth of both the babies, intramyometrial injections of
      Carboprost and Pitocin were administered. Immediately, she suffered cardiac
      arrest. Cardio pulmonary resucitation (CPR) was started and within 3 minutes, she
      was successfully resuscitated. The patient initially showed peculiar
      psychological changes and with passage of time, certain psycho-behavioural
      patterns emerged which could be attributed to near death experiences, as
      described in this case report.

PMID- 21189889
TI  - Subdural haematoma in pregnancy-induced idiopathic thrombocytopenia: Conservative
      management.
AB  - Conservative management of subdural haematoma with antioedema measures in second
      gravida with idiopathic thrombocytopenic purpura (ITP) resulted in resolution of
      haematoma. We present a case of second gravida with ITP who developed subdural
      haematoma following normal vaginal delivery. She was put on mechanical
      ventilation and managed conservatively with platelet transfusion, Mannitol 1g/kg,
      Dexamethasone 1mg/kg and Glycerol 10ml TDS. She regained consciousness and was
      extubated after 48 hrs. Repeat CT after 10 days showed no mass effect with
      resolving haematoma which resolved completely after 15 days. Trial of
      conservative management is safe in pregnant patient with ITP who develops
      subdural haematoma.

PMID- 21189890
TI  - Facial nerve involvement in critical illness polyneuropathy.
AB  - Although ICU-acquired neuromuscular weakness is a well-known problem, critical
      illness neuropathy is an under-diagnosed entity in critically ill patients.
      Facial musculature is typically not involved in critical illness neuropathy. This
      report highlights an unusual presentation of critical illness polyneuropathy in a
      patient with involvement of facial musculature.

PMID- 21189891
TI  - Sir Thomas Lauder Brunton, F.R.S. (1844-1916) about his visit to Hyderabad -
      Deccan: His role in the 2 Hyderabad Chloroform Commission (1889 A.D.).
AB  - Hundred years ago in Great Britain, Sir Thomas Lauder Brunton was acclaimed as an
      authority on the action of drugs on the heart. His famous work, "Pharmacology and
      Therapeutics" (1867), was read and appreciated all over Europe and America. He
      stated that nitrite of amyl has a beneficial effect on the heart. This led to the
      discovery of many other nitrite compounds that are now used for the treatment of
      angina pectoris. He also stated that mitral stenosis should be treated by
      surgery, i.e. by splitting the stenosed cusps. This statement paved the way for
      cardiac surgeons to devise the technique of closed mitral valvotomy. The results
      were encouraging and closed mitral valvotomy became the sheet anchor of treatment
      for a majority of the cases of mitral stenosis.

PMID- 21189892
TI  - Management of neonatal giant occipital encephalocele: Anaesthetic challenge.

PMID- 21189893
TI  - Transcutaneous electrical nerve stimulation to reduce pain in post-op thoracotomy
      patients: A physical therapists' perspective.

PMID- 21189894
TI  - Cannot ventilate, Can we intubate?

PMID- 21189895
TI  - Locked-in syndrome after stellate ganglion block.

PMID- 21189896
TI  - Damaged ProsealTM LMA inflation line can be repaired.

PMID- 21189897
TI  - Estimation of the dose of hyperbaric bupivacaine for spinal anaesthesia for
      emergency caesarean section in an achondroplastic dwarf.

PMID- 21189898
TI  - Extensive deep vein thrombosis in a young parturient with a brief use of oral
      contraceptive pills.

PMID- 21189899
TI  - Challenges in pharmacovigilance.

PMID- 21189900
TI  - Role of coenzyme Q(10) as an antioxidant and bioenergizer in periodontal
      diseases.
AB  - Periodontal disease is an inflammatory disease process resulting from the
      interaction of a bacterial attack and host inflammatory response. Arrays of
      molecules are considered to mediate the inflammatory response at one time or
      another, among these are free radicals and reactive oxygen species (ROS).
      Periodontal pathogens can induce ROS overproduction and thus may cause collagen
      and periodontal cell breakdown. When ROS are scavenged by antioxidants, there can
      be a reduction of collagen degradation. Ubiquinol (reduced form coenzyme Q(10))
      serves as an endogenous antioxidant which increases the concentration of CoQ(10)
      in the diseased gingiva and effectively suppresses advanced periodontal
      inflammation.

PMID- 21189901
TI  - Novel technologies: A weapon against tuberculosis.
AB  - Tuberculosis (TB) is a leading chronic bacterial infection. Despite potentially
      curative pharmacotherapies being available for over 50 years, the length of the
      treatment and the pill burden can hamper patient lifestyle. Low compliance and
      adherence to administration schedules remain the main reasons for therapeutic
      failure and contribute to the development of multidrug-resistant strains. The
      design of novel antibiotics attempts to overcome drug resistance, to shorten the
      treatment course, and to reduce drug interactions. In this framework,
      nanotechnology appears as one of the promising approaches for the development of
      more effective medicines. The present review thoroughly overviews the development
      of novel microparticulate, encapsulation, and various other carrier-based drug
      delivery systems for incorporating the principal anti-TB agents. Drug delivery
      systems have been designed that either target the site of TB or reduce the dosing
      frequency with the aim of improving patient healthcare.

PMID- 21189902
TI  - Ruta graveolens L. toxicity in Vampirolepis nana infected mice.
AB  - OBJECTIVE: To determine possible toxic effects of Ruta graveolens hydroalcoholic
      extract in gastrointestinal parasitic infection. MATERIALS AND METHODS: A total
      of 100 g plant leaves and seeds were powdered and extracted with 1500 mL
      alcohol/water and administered by gavage to Swiss albino mice infected with
      Vampirolepis nana. Anti-parasitic evaluation and toxicity assays were carried out
      in six groups of ten animals each. Treatments were scheduled with both the leaves
      and the seeds' extracts at doses of 2.5, 5, and 10 mg per gram body weight.
      Toxicity was comparatively analyzed to a vehicle control group (n = 10) and to a
      Praziquantel((r)) treated. On the fifth day, all the individuals were killed by
      euthanasia and parasite scores were correlated, giving rise to a relative
      percentage of elimination to each treatment. Toxicity was achieved by hematology
      and by clinical chemistry determinations. RESULTS: The use of the R. graveolens
      hydroalcoholic extract to treat V. nana infected mice resulted in a mild-to
      moderate hepatoxicity associated to a poor anti-parasitic effect. The major
      proglottids elimination (E%) was achieved at the lowest crude extract
      concentration with a mild anti-parasitic efficacy from the highest dose; that did
      not cause a significant elimination of parasites. A decrease of circulating
      polymorphonuclear-neutrophils associated with a normochromic-normocytic anemia
      was detected as the extract dose was augmented. The blood aspartate
      aminotransferase and alanine-aminotransferase tended be slightly augmented with
      100 mg R. graveolens extract. CONCLUSION: R. graveolens is an unsafe natural anti
      parasitic medicine as its active constituents may be poorly extracted by the
      popular crude herb infusion. Although it presented a mild anti-parasitic effect
      in mice, symptoms of natural-products-induced-liver-disease confirmed that its
      self-medication should be avoided.

PMID- 21189903
TI  - Elevation of antidermatophytic action of mefenamic acid by cobalt ions.
AB  - OBJECTIVES: To evaluate the antifungal property of mefenamic acid, which is a
      member of non-steroidal anti-inflammatory drugs (NSAIDs) group. MATERIALS AND
      METHODS: In order to evaluate the antifungal property of mefenamic acid on
      dermatophytes, it was mixed with cobalt (Co) in culture media. Two species
      related to two genera of dermatophytes were tested for their susceptibility to
      mefenamic acid and its complex with Co by using colony diameter measurement
      method. RESULTS: The inhibitory action of mefenamic acid on fungal strains was
      increased in the presence of Co. Epidermophyton floccosum showed more susceptibly
      to either mefenamic acid or its complex with Co than Trichophyton mentagrophytes
      variant mentagrophytes. CONCLUSIONS: Mefenamic acid showed potential ability to
      prevent growth of dermatophytes. This ability increased due to the presence of
      Co.

PMID- 21189904
TI  - Comparison of analgesic effects of nimesulide, paracetamol, and their combination
      in animal models.
AB  - OBJECTIVES: To compare the analgesic activity of nimesulide and paracetamol alone
      and their combination in animal models for the degree of analgesia and the time
      course of action. MATERIALS AND METHODS: Analgesia was studied in albino rats
      using formalin test and in albino mice using writhing test and the radiant heat
      method. For each test, four groups of six animals each were orally fed with a
      single dose of nimesulide, paracetamol, and combination of nimesulide +
      paracetamol and gum acacia as control, respectively. RESULTS: In all the three
      test models, all three drug treatments showed significant analgesia (P < 0.001)
      as compared to control, but there was no significant difference in the analgesia
      produced by either drugs alone or in combination. The radiant heat method
      demonstrated a quicker onset and longer duration of action with nimesulide,
      whereas writhing test showed a quicker onset of action with paracetamol. In
      formalin test, greater degree of analgesia was seen with individual drugs than
      that of the combination, though this difference was not statistically
      significant. CONCLUSIONS: Nimesulide and paracetamol combination offers no
      advantage over nimesulide alone or paracetamol alone, either in terms of degree
      of analgesia or onset of action. Therefore, our study supports the reports
      claiming irrationality of the fixed dose combination of nimesulide and
      paracetamol.

PMID- 21189905
TI  - Evaluation of efficacy of combination of methotrexate and hydroxychloroquine with
      leflunomide in active rheumatoid arthritis.
AB  - BACKGROUND: Several new drugs for rheumatoid arthritis are available including
      leflunomide. Comparative studies of treatment with leflunomide (against
      methotrexate) report a better quality of life. AIM: This study was designed to
      evaluate the efficacy of combination of methotrexate and hydroxychloroquine with
      leflunomide, a new disease modifying antirheumatoid drug. Analysis was of intent
      to treat group. MATERIALS AND METHODS: This was an open labeled, randomized,
      comparative clinical trial in the department of rheumatology and immunology, at a
      tertiary care center in Bangalore. Patients who have diagnosed with rheumatoid
      arthritis as per American College of Rheumatology aged between 18 and 60 years
      were recruited and randomized to receive leflunomide (10 mg/day p.o.) or a
      combination of methotrexate and hydroxychloroquine (7.5 mg/week p.o. and 200
      mg/day p.o., respectively) along with folate supplementation for 12 weeks. The
      European League Against Rheumatism criteria of improvement according to disease
      activity score 28 was considered as the primary efficacy variable. Baseline and
      end of study values were evaluated. The duration of the study period was 1 year.
      Analysis of variance (ANOVA) and Wilcoxon Signed rank test were used for
      statistical analysis. RESULTS: After 12 weeks, improvement noted in patients
      treated with leflunomide was similar to those treated with a combination of
      methotrexate and hydroxychloroquine. There was no statistical significance in
      improvement in disease activity between the two groups (P = 0.377). CONCLUSION:
      Combination of methotrexate and hydroxychloroquine is equivalent to leflunomide
      in terms of efficacy in reducing disease activity in the initial treatment of
      severe rheumatoid arthritis.

PMID- 21189906
TI  - A comparative study on the efficacy, safety, and cost-effectiveness of
      bimatoprost/timolol and dorzolamide/timolol combinations in glaucoma patients.
AB  - AIM: This study was designed to compare the bimatoprost/timolol combination and
      dorzolamide/timolol combination in glaucoma for efficacy, safety, and cost
      effectiveness in a local population of Trichy in the state of Tamilnadu.
      MATERIALS AND METHODS: Eight-week, randomized, parallel group, open-label study
      was conducted on 48 patients of open angle glaucoma or ocular hypertension. After
      initial clinical assessment and baseline investigations, bimatoprost/timolol
      combination (Group A) was prescribed to 22 patients (2 patients lost after
      initial assessment) and dorzolamide/timolol combination (Group B) to 24 patients.
      The patients were reviewed after second and eighth weeks for cure rate and
      adverse drug reaction monitoring. RESULTS: At the end of 8 weeks, the mean
      reduction in intraocular pressure from baseline was 13.04 mmHg (95% confidence
      interval (CI): 10.67-14.70) with bimatoprost/timolol combination once daily (P <
      0.01) and 9.46 mmHg (95% CI: 7.47-10.5) with dorzolamide/timolol combination
      twice daily. Both the treatments were safe. Cost-effective range of
      bimatoprost/timolol combination was lower than that of dorzolamide/timolol
      combination. CONCLUSION: The fixed combination of bimatoprost/timolol was
      slightly more effective than that of dorzolamide/timolol combination in reducing
      IOP, and both treatments were generally well tolerated. Bimatoprost/timolol
      combination was more cost-effective (cost-effective analysis) than
      dorzolamide/timolol combination.

PMID- 21189907
TI  - QTc interval prolongation by fexofenadine in healthy human volunteers and its
      correlation with plasma levels of fexofenadine: A demonstration of anticlockwise
      hysteresis.
AB  - AIM: The study was designed to establish relationship between the plasma
      concentration and QTc interval prolonging effect of fexofenadine and demonstrate
      the phenomenon of anticlockwise hysteresis. MATERIALS AND METHODS: Six subjects
      were given fexofenadine 60 mg tablet orally under stable conditions, and their
      drug concentrations were measured at regular intervals. At predetermined time,
      their ECGs were recorded. Data were analyzed and plotted graphically. DESIGN AND
      SETTING: Randomized parallel design, single group study conducted at clinical
      research organization of Ahmadabad. RESULTS: In all subjects time taken for
      maximum plasma concentration of fexofenadine (T(max)) was around 3 h and the
      value of average maximum plasma concentration was 460.63 ng/mL, the effect of
      fexofenadine on the heart (measured as QTc interval prolongation) was maximum
      (E(max)) after 6 h and average QTc interval was 469.75 ms. Thus, the time to
      maximum concentration of fexofenadine did not match with the maximum effect on
      the heart as measured by QTc interval. CONCLUSION: The relationship between the
      drug concentration and drug effect on the heart are at two different time scales.
      It can be understood by two-compartment model of pharmacokinetics, and this
      retardation or lagging of an effect behind the concentration is known as
      hysteresis. The increase of QTc was not beyond 500 ms and not sustained,
      demonstrating overall cardiac safety of fexofenadine.

PMID- 21189908
TI  - Amelioration effects against N-nitrosodiethylamine and CCl(4)-induced
      hepatocarcinogenesis in Swiss albino rats by whole plant extract of Achyranthes
      aspera.
AB  - OBJECTIVE: The prevalence of oxidative stress may be implicated in the etiology
      of many pathological conditions. Protective antioxidant action imparted by many
      plant extracts and plant products make them a promising therapeutic drug for free
      radical-induced pathologies. In this study, we assessed the antioxidant potential
      and suppressive effects of Achyranthes aspera by evaluating the hepatic
      diagnostic markers on chemical-induced hepatocarcinogenesis. MATERIALS AND
      METHODS: The in vivo model of hepatocarcinogenesis was studied in Swiss albino
      rats. Experimental rats were divided into five groups: control, positive control
      (NDEA and CCl(4)), A. aspera treated (100, 200, and 400 mg/kg b.w.). At 20 weeks
      after the administration of NDEA and CCl(4), treated rats received A. aspera
      extract (AAE) at a dose of 100, 200, and 400 mg/kg once daily route. At the end
      of 24 weeks, the liver and relative liver weight and body weight were estimated.
      Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione
      peroxidase (GPx), glutathione-S-transferase (GST), and reduced glutathione (GSH)
      were assayed. The hepatic diagnostic markers namely serum glutamic oxaloacetic
      transminase (AST), serum glutamic pyruvate transminase (ALT), serum alkaline
      phosphatase (ALP), gamma glutamyl transpeptidase (GGT), and bilirubin (BL) were
      also assayed, and the histopathological studies were investigated in control,
      positive control, and experimental groups. RESULTS: The extract did not show
      acute toxicity and the per se effect of the extract showed decrease in LPO,
      demonstrating antioxidant potential and furthermore no change in the hepatic
      diagnosis markers was observed. Administration of AAE suppressed hepatic
      diagnostic and oxidative stress markers as revealed by decrease in NDEA and
      CCl(4) -induced elevated levels of SGPT, SGOT, SALP, GGT, bilirubin, and LPO.
      There was also a significant elevation in the levels of SOD, CAT, GPx, GST, and
      GSH as observed after AAE treatment. The liver and relative liver weight were
      decreased after treatment with AAE in comparison to positive control group. The
      architecture of hepatic tissue was normalized upon treatment with extract at
      different dose graded at 100, 200, and 400 mg/kg. b.w. in comparison to positive
      control group. CONCLUSION: These results suggest that A. aspera significantly
      alleviate hepatic diagnostic and oxidative stress markers which signify its
      protective effect against NDEA and CCl(4)-induced two-stage hepatocarcinogenesis.

PMID- 21189909
TI  - Olanzapine-induced hepatopathy in albino rats: A newer model for screening
      putative hepatoprotective agents, namely silymarin.
AB  - BACKGROUNDS: This study was conducted to establish olanzapine-induced hepatopathy
      in Wistar albino rats as a newer model to screen putative hepatoprotective agents
      namely silymarin. MATERIALS AND METHODS: Albino rats were divided into three
      groups, namely vehicle control group (CG), olanzapine-treated group (OZ), and
      olanzapine plus silymarin (OZS) treated groups. Both the OZ and OZS groups were
      treated with the same dose of intraperitoneal olanzapine for 6 weeks and group
      OZS additionally received oral silymarin. Baseline and terminal hepatic enzymes
      (SGOT, SGPT, and ALP) were measured in all three groups. RESULTS:
      Histopathological examination of livers of both OZ and OZS groups showed
      degenerative changes, whereas those of control group showed normal architecture.
      Liver enzyme levels showed statistically significant rise in comparison to the
      control group as well as the respective base line values in both the test groups,
      but the differences in the rise of liver enzymes between the two test groups were
      not statistically significant. CONCLUSION: Olanzapine-induced hepatopathy in rats
      can be used as a model for screening putative hepatoprotective agents and in our
      setting silymarin has failed to provide any hepatoprotection.

PMID- 21189910
TI  - Antiurolithiatic and antioxidant activity of Mimusops elengi on ethylene glycol
      induced urolithiasis in rats.
AB  - OBJECTIVE: To evaluate the potential of Mimusops elengi in the treatment of renal
      calculi. MATERIALS AND METHODS: Petroleum ether, chloroform, and alcohol extracts
      of Mimusops elengi bark were evaluated for antiurolithiatic and antioxidant
      activity in male albino Wistar rats. Ethylene glycol (0.75%) in drinking water
      was fed to all the groups (Groups II-IX) except normal control (Group I) for 28
      days to induce urolithiasis for curative (CR) and preventive (PR) regimen. Groups
      IV, V, and VI served as CR, and groups VII, VIII, and IX as PR were treated with
      different extracts of M. elengi bark. Groups I, II, and III served as normal
      control, positive control (hyperurolithiatic), and standard (cystone 750 mg/kg),
      respectively. Oxalate, calcium, and phosphate were monitored in the urine and
      kidney. Serum BUN, creatinine, and uric acid were also recorded. In vivo
      antioxidant parameters such as lipid peroxidation (MDA), glutathione (GSH),
      superoxide dismutase (SOD), and catalase (CAT) were also monitored. RESULTS: All
      the extracts of M. elengi were safe orally and exhibited no gross behavioral
      changes in the rats. In hypercalculi animals, the oxalate, calcium, and phosphate
      excretion grossly increased. However, the increased deposition of stone forming
      constituents in the kidneys of calculogenic rats were significantly (P < 0.001)
      lowered by curative and preventive treatment with alcohol extract (AlE) of M.
      elengi. It was also observed that alcoholic extract of M. elengi produced
      significant (P < 0.001) decrease in MDA, and increased GSH, SOD, and CAT. These
      results confirm that AlE of M. elengi possess potent antiurolithiatic activity.
      CONCLUSION: The results obtained suggest potential usefulness of the AlE of M.
      elengi bark as an antiurolithiatic agent.

PMID- 21189911
TI  - Effect of l-ornithine l-aspartate against thioacetamide-induced hepatic damage in
      rats.
AB  - OBJECTIVE: To investigate the hepatoprotective activity of L-ornithine-L
      aspartate against thioacetamide (TAA)-induced hepataopathy in rats. MATERIALS AND
      METHODS: The hepatoprotective activity of L-ornithine-L-aspartate (OA) at a dose
      of 2 g/kg, p.o. for 10 days was evaluated against TAA (250 mg/kg, i.p. for 2
      days) induced hepatopathy in rats. Biochemical parameters such as serum aspartate
      transaminase, alanine transaminase, alkaline phosphatase, bilirubin and
      glutathione, thiobarbituric acid reactive substances, and protein in liver
      tissues were estimated to assess the liver function. RESULTS: TAA-induced
      pathogenic changes in the levels of the above indices were significantly (P <
      0.01) reversed by the OA treatment. OA treatment also exhibited significant
      restoration of the hepatic architecture and lobular structure in histological
      evaluation of the rat liver sections. CONCLUSION: Ornithine aspartate exhibited
      significant hepatoprotective activity against TAA-induced hepatic damage in rats.

PMID- 21189912
TI  - Effects of Phyllanthus reticulatus on lipid profile and oxidative stress in
      hypercholesterolemic albino rats.
AB  - OBJECTIVE: This study was designed to investigate the effect of Phyllanthus
      reticulatus on lipid profile and oxidative stress in hypercholesterolemic albino
      rats. MATERIALS AND METHODS: Hypercholesterolemia was induced in albino rats by
      administration of atherogenic diet for 2 weeks. Experimental rats were divided
      into different groups: normal, hypercholesterolemic control and P. reticulatus
      treated (250 and 500 mg/kg body weight doses for 45 days). After the treatment
      period of 45(th) day triglyceride, VLDL-cholesterol, HDL-cholesterol, total
      cholesterol (TC), LDL-cholesterol and oxidative stress (protein carbonyl) were
      assayed and compared with hypercholesterolemic control. RESULTS: The aqueous
      extract of P. reticulatus (250 mg and 500 mg/kg) produced significant reduction
      (P < 0.05) in triglyceride, VLDL-cholesterol, total cholesterol (TC), LDL
      cholesterol and oxidative stress (protein carbonyl) while increased HDL
      cholesterol in atherogenic diet-induced hypercholesterolemic rats at the end of
      the treatment period (45 days). However, the reduction in the above parameters
      was comparable with hypercholesterolemic control. Thus, aqueous extract of P.
      reticulatus is effective in controlling TC, lipid profile and oxidative stress in
      hypercholesterolemic animals. CONCLUSION: The results suggest the aqueous extract
      of P. reticulatus can be utilized for prevention of atherosclerosis in
      hypercholesterolemic patients.

PMID- 21189913
TI  - The study of aqueous extract of Pterocarpus marsupium Roxb. on cytokine TNF-alpha
      in type 2 diabetic rats.
AB  - OBJECTIVE: This study was designed to investigate the effect of aqueous extract
      of Pterocarpus marsupium Roxb. on elevated inflammatory cytokine, tumor necrosis
      factor (TNF)-alpha in type 2 diabetic rats. MATERIALS AND METHODS: Type 2
      diabetes was induced by administering streptozotocin (90 mg/kg, i.p.) in a
      neonatal rat model. Aqueous extract of P. marsupium at a dose of 100 and 200
      mg/kg was given orally to desired group of animals for a period of 4 weeks. After
      4 weeks of drug treatment, parameters such as fasting blood glucose, postprandial
      blood glucose, and TNF-alpha in serum were analyzed. RESULTS: Aqueous extract of
      P. marsupium at both doses, i.e., 100 and 200 mg/kg, decreased the fasting and
      postprandial blood glucose in type 2 diabetic rats. The 200 mg/kg had more
      pronounced effect on postprandial hyperglycemia. The drug also improved the body
      weight of diabetic animals. Cytokine TNF-alpha was found to be elevated in
      untreated diabetic rats due to chronic systemic inflammation. The aqueous extract
      at both doses significantly (P < 0.001) decreased the elevated TNF-alpha level in
      type 2 diabetic rats. CONCLUSION: Modulation of cytokine TNF-alpha by the
      rasayana drug P. marsupium is related with its potential anti-diabetic activity.

PMID- 21189914
TI  - Evaluation of hepatoprotective activity of Cissus quadrangularis stem extract
      against isoniazid-induced liver damage in rats.
AB  - OBJECTIVE: The study was designed to investigate the hepatoprotective activity of
      methanol extract of Cissus quadrangularis (CQ) against isoniazid-induced
      hepatotoxicity in rats. MATERIALS AND METHODS: The successive petroleum ether (60
      80 degrees C) and methanol extracts of C. quadrangularis were used. Hepatic
      damage was induced in Wistar rats by administering isoniazid (54 mg/kg, p.o.)
      once daily for 30 days. Simultaneously, CQ (500 mg/kg p.o) was administered 1 h
      prior to the administration of isoniazid (54 mg/kg, p.o.) once daily for 30 days.
      Silymarin (50 mg/kg p.o) was used as a reference drug. RESULTS: Elevated levels
      of aspartate transaminase, alanine transaminase, alkaline posphatase, and
      bilirubin following isoniazid administration were significantly lowered due to
      pretreatment with CQ. Isoniazid administration significantly increased lipid
      peroxidation (LPO) and decreased antioxidant activities such as reduced
      glutathione, superoxide dismutase, and catalase. Pretreatment of rats with CQ
      significantly decreased LPO and increased the antioxidant activities. CONCLUSION:
      The results of this study indicated that the hepatoprotective effect of CQ might
      be attributed to its antioxidant property.

PMID- 21189915
TI  - A comparative study of nebivolol and (S) atenolol on blood pressure and heart
      rate on essential hypertensive patients.
AB  - OBJECTIVES: To study the effect of nebivolol 5 mg once daily versus (S)-atenolol
      25 mg once daily in patients with essential hypertension. MATERIALS AND METHODS:
      A prospective study was conducted at RLJH and Research Centre which included 30
      patients in each group with essential hypertension. The sex, age, presenting
      illness, and family history of the patients were recorded. Investigations such as
      blood sugar, urine analysis, kidney function test, lipid profile, and ECG were
      performed before starting the treatment. Any adverse effects during the treatment
      were noted. Blood pressure and heart rate were recorded at baseline and during
      follow-up. One group received nebivolol 5 mg once daily and other group
      (S)atenolol 25 mg once daily. Patients were followed-up every 15 days for 3
      months. RESULTS: Nebivolol group had 18 males and 12 females with mean age 50.6
      +/- 9.5 years, (S)-atenolol had 16 males and 14 females with mean age 54.4 +/- 9
      years. Patients receiving nebivolol and (S)-atenolol showed a significant fall (P
      <.0001) in systolic (SBP), diastolic blood pressure (DBP), and heart rate at the
      end of first, second, and third month when compared to baseline. The difference
      in fall in SBP and DBP was insignificant between the groups, but fall in heart
      rate was significant (P <.0001). Adverse effects such as headache, dizziness, and
      fatigue were reported with both drugs. CONCLUSION: Reduction of blood pressure
      with nebivolol and (S)atenolol was similar, but fall in blood pressure from
      baseline was highly significant in both groups.

PMID- 21189916
TI  - Effect of calcium on anxiolytic activity of diazepam and verapamil in rats.
AB  - OBJECTIVE: To analyze the role of calcium in anxiety and its effect on anxiolytic
      activity of diazepam and verapamil. MATERIALS AND METHODS: Study was conducted
      using female albino rats in light and dark arena; a nonconflicting animal
      experimental model for anxiety. Animals were divided into six groups with six
      animals in each group. Test drugs, calcium gluconate (10 mg/kg), diazepam (1
      mg/kg), verapamil (5 mg/kg), calcium + diazepam, and calcium + verapamil were
      administered intraperitoneally. Percentage of time spent in light arena and
      number of entries into light arena were the two parameters observed for 5 min
      after 30 min of drug administration. ANOVA test was used for statistical
      analysis. RESULTS: Compared to the control group, diazepam group, and calcium
      group, only calcium + diazepam group showed considerable increase in mean
      percentage of time spent in light arena. However, this increase was statistically
      insignificant. In the case of total number of entries into light arena, animals
      in calcium + diazepam group showed statistically significant increase in total
      number of entries into light arena when compared to calcium group and diazepam
      group. CONCLUSION: Results of the study suggest that calcium may enhance the
      anxiolytic activity of diazepam, but has no effect on anxiolytic activity of
      verapamil.

PMID- 21189917
TI  - Screening of anti-inflammatory and antipyretic activity of Vitex leucoxylon Linn.
AB  - OBJECTIVE: This study was designed to evaluate the anti-inflammatory and
      antipyretic activity of ethyl acetate extract of Vitex leucoxylon Linn. in
      various animal experimental models. MATERIALS AND METHODS: Ethyl acetate extract
      of V. leucoxylon Linn. evaluated for anti-inflammatory activity in carrageenan,
      mediator-induced rat paw edema, and cotton pellet-induced granuloma model. The
      antipyretic activity was evaluated by yeast-induced pyrexia model. RESULTS:
      Single administration of the ethyl acetate extract of V. leucoxylon Linn. at dose
      of 500 mg/kg p.o. showed significant (P < 0.001) inhibition of rat paw edema. The
      ethyl acetate extract showed significant antipyretic activity in brewer yeast
      induced pyrexia in rats throughout the observation period of 4 h. CONCLUSION:
      This study shows that ethyl acetate extract of V. leucoxylon Linn. has
      significant anti-inflammatory and antipyretic activity.

PMID- 21189918
TI  - Therapeutic misadventure with paracetamol in children.
AB  - Paracetamol (acetaminophen), though considered a safe, "over the counter"
      analgesic and antipyretic, can cause liver injury with overdose. Therapeutic
      misadventure is a unique problem where the existing nomogram used for acute
      poisoning is not applicable. In this context, early initiation of N
      acetylcysteine even before a biochemical evidence of liver injury may be
      beneficial. A series of 6 children with this type of paracetamol overdose are
      presented here to increase the awareness and understanding of this problem since
      no such data is available from India.

PMID- 21189919
TI  - Acute akathisia with quetiapine: A case report and review of literature.
AB  - Quetiapine is an atypical antipsychotic which has been shown to have greater
      relative affinity for 5-HT(2A) receptors than for D(2) receptors, due to which it
      is thought to lead to lower incidence of extrapyramidal symptoms (EPS). However,
      over the years literature in the form of case reports have accumulated which
      shows that quetiapine can lead to akathisia, especially in subjects prone to
      develop EPS. In this study, we report the case of a 22-year-old female who
      developed akathisia with quetiapine 150 mg/day, which subsided with reduction in
      dose. We have also reviewed the existing literature with respect to akathisia
      with quetiapine.

PMID- 21189920
TI  - An interesting case of serotonin syndrome precipitated by escitalopram.
AB  - Serotonin syndrome is a known entity, which occurs with multiple drugs acting on
      serotonergic receptors. A 73-year-old lady presented with a history of agitation,
      altered sensorium, and autonomic hyperactivity after starting escitalopram on
      therapeutic dosage for her depressive syndrome who was on selegiline for her
      parkinsonism. This syndrome with therapeutic dose escitalopram warrants the
      careful and judicious use of the drug especially with other serotonergic drugs,
      so that this serious medical complication can be avoided.

PMID- 21189921
TI  - An imperative need to change pharmacology curriculum: A pilot survey.

PMID- 21189922
TI  - Rational use of medicines: How the armed forces do it.

PMID- 21189923
TI  - Very-low-birth-weight infants, prophylactic micafungin or fluconazole.

PMID- 21189924
TI  - Echinocandins: A ray of hope in antifungal drug therapy.

PMID- 21189925
TI  - Announcement of publication of the Korean Journal of Pediatrics in English.

PMID- 21189926
TI  - Enterovirus 71 infection: An experience in Korea, 2009.
AB  - Enterovirus 71 (EV71) has been recognized as a frequent cause of epidemics of
      hand-foot-and-mouth disease (HFMD) associated with severe neurological symptoms.
      In the spring of 2009, HFMD was epidemic in Korea. Severe cases with
      complication, including death, have been reported and it has become a public
      health issue. Most symptomatic EV71 infections commonly result in HFMD or
      herpangina. These clinical manifestations can be associated with neurologic
      syndromes frequently. Neurologic syndromes observed in EV71 include meningitis,
      meningoencephalomyelitis, poliomyelitis-like paralytic disease, Guillain-Barre
      syndrome, transverse myelitis, cerebellar ataxia, opsoclonus-myoclonus syndrome,
      benign intracranial hypertension, and brainstem encephalitis. Examinations for EV
      71 were performed from the stools, respiratory secretion or CSF of the children
      by realtime PCR. Gene analysis showed that most of them were caused by EV71
      subgenotype C4a which was prevalent in China, 2008. Public health measures
      including personal and environmental hygiene, must to target daycare centers,
      kindergartens, and schools where highly susceptible children congregate. To
      prevent the spread of infection, preschools where transmission persists for more
      than 2 incubation periods, have been recommended for closure, and trigger
      criteria for voluntary closure was instituted. During closure, operators are to
      thoroughly clean the centers before they are allowed to reopen. In addition,
      parents are advised to ensure that their children adopt a high standard of
      personal hygiene and to keep the infected child at home until full recovery.
      Because the outbreaks occur in a cyclical pattern, surveillance system to predict
      next outbreaks and adequate public health measures to control need to be planned
      for future. Control of EV71 epidemics through surveillance and public health
      intervention needs to be maintained in Korea. Future research should focus on
      understanding of EV71 virulence, identification of the receptor(s) for EV71,
      development of antiviral agents and development of vaccine.

PMID- 21189927
TI  - Reemergence of mumps.
AB  - The mumps virus is a single-stranded, non-segmented, negative-sense RNA virus
      belonging to the Paramyxoviridae family. Mumps is characterized by bilateral or
      unilateral swelling of the parotid gland. Aseptic meningitis is a common
      complication, and orchitis is also common in adolescents and adult men. Diagnosis
      is based on clinical findings, but because of high vaccination coverage, clinical
      findings alone are not sufficient for diagnosis, and laboratory confirmation is
      needed. Mumps is preventable by vaccination, but despite high vaccination
      coverage, epidemics occur in several countries, including Korea. Many hypotheses
      are suggested for these phenomena. In this review, we investigate the reason for
      the epidemics, optimal methods of diagnosis, and surveillance of immunization
      status for the prevention of future epidemics.

PMID- 21189928
TI  - Update on pertussis and pertussis immunization.
AB  - Pertussis is a highly contagious respiratory tract disease caused by Bordetella
      pertussis infection. The clinical manifestation of this infection can be severe
      enough to cause death. Although pertussis has been supposed to be a vaccine
      preventable disease ever since the widespread vaccination of children against
      pertussis was started, since the 1990s, cases of pertussis and related fatalities
      are on the rise, especially in countries with high vaccination coverage. In
      Korea, there have been no deaths due to pertussis since 1990, and the vaccination
      rate continues to be approximately 94%. However, the number of pertussis cases
      reported to the Korea Center for Disease Control and Prevention has tended to
      increase in the 2000s, and in 2009, there was an obvious increase in the number
      of pertussis cases reported. This review aims to present the latest information
      about the pathogenesis, diagnosis, treatment, and prevention of pertussis.

PMID- 21189929
TI  - Complete rooming-in care of newborn infants.
AB  - PURPOSE: In Kyung Hee East-West Neo Medical Center, Seoul, Korea, efforts to
      raise rooming-in care success rate have been undertaken since when the hospital
      was established in 2006. We intended to analyze our experience over the past 3
      years of period and to discuss the advantages of rooming-in. METHODS: We analyzed
      the rooming-in practice rate, failure rate, and the breast feeding rate. Subjects
      were 860 normal healthy neonates from June 2006 to June 2009. RESULTS: Among
      these 860 cases, 83 babies were required separation out of rooming-in in the
      middle of the course. Among these 83 cases, 70 cases had to stop the course due
      to poor condition of babies and 13 cases due to maternal condition. 70 cases of
      infant's causes consist of 68 cases of NICU admission and 2 cases of poor feeding
      support. The other 13 cases of separation include refusal by maternal condition.
      Therefore the success rate of rooming-in for the last 3 years was 90.3%, that is
      777 cases among the total 860 cases. The percentage of exclusive breast feeding
      was 64%, that of mixed feeding with breast and formula feeding was 25%, and
      formula feeding only was 11%. CONCLUSION: We experienced successful rooming-in
      care for the last 3 years. Nursery facilities should educate and encourage the
      advantages of rooming-in, including the good formation of attachment between
      mother and infant, emotional stability, protection from infection, and increased
      breast feeding rate so that rooming-in care can be fully established.

PMID- 21189930
TI  - Enterovirus 71-associated hand, foot and mouth diseases with neurologic symptoms,
      a university hospital experience in Korea, 2009.
AB  - PURPOSE: Hand-foot-mouth disease (HFMD) is a common viral illness in children,
      which is usually mild and self-limiting. However, in recent epidemics of HFMD in
      Asia, enterovirus 71 (EV71) has been recognized as a causative agent with severe
      neurological symptoms with or without cardiopulmonary involvement. HFMD was
      epidemic in Korea in the spring of 2009. Severe cases with complications
      including death have been reported. The clinical characteristics in children with
      neurologic manifestations of EV71 were studied in Ewha Womans University Mokdong
      Hospital. METHODS: Examinations for EV71 were performed from the stools,
      respiratory secretion or CSF of children who presented neurologic symptoms
      associated with HFMD by realtime PCR. Clinical and radiologic data of the
      patients were collected and analyzed. RESULTS: EV71 was isolated from the stool
      of 16 patients but not from respiratory secretion or CSF. Among the 16 patients,
      meningitis (n=10) was the most common manifestation, followed by Guillain-Barre
      syndrome (n=3), meningoencephalitis (n=2), poliomyelitis-like paralytic disease
      (n=1), and myoclonus (n=1). Gene analysis showed that most of them were caused by
      EV71 subgenotype C4a, which was prevalent in China in 2008. CONCLUSION: Because
      EV71 causes severe complications and death in children, a surveillance system to
      predict upcoming outbreaks should be established and maintained and adequate
      public health measures are needed to control disease.

PMID- 21189932
TI  - Brain abscess in Korean children: A 15-year single center study.
AB  - PURPOSE: A brain abscess is a serious disease of the central nerve system. We
      conducted this study to summarize the clinical manifestations and outcomes of
      brain abscesses. METHODS: A retrospective chart review of pediatric patients
      diagnosed with brain abscesses from November 1994 to June 2009 was performed at
      Samsung Medical Center, Seoul, Korea. RESULTS: Twenty-five patients were included
      in this study. On average, 1.67 cases per year were identified and the median age
      was 4.3 years. The common presenting clinical manifestations were fever (18/25,
      72%), seizure (12/25, 48%), altered mental status (11/25, 44%), and signs of
      increased intracranial pressure (9/25, 36%). A total of 14 (56%) patients had
      underlying illnesses, with congenital heart disease (8/25, 32%) as the most
      common cause. Predisposing factors were identified in 15 patients (60%). The
      common predisposing factors were otogenic infection (3/25, 12%) and penetrating
      head trauma (3/25, 12%). Causative organisms were identified in 64% of patients
      (16/25). The causative agents were S. intermedius (n=3), S. aureus (n=3), S.
      pneumoniae (n=1), Group B streptococcus (n=2), E. coli (n=1), P. aeruginosa
      (n=1), and suspected fungal infection (n=5). Seven patients received medical
      treatment only while the other 18 patients also required surgical intervention.
      The overall fatality rate was 16% and 20% of patients had neurologic sequelae.
      There was no statistical association between outcomes and the factors studied.
      CONCLUSION: Although uncommon, a brain abscess is a serious disease. A high level
      of suspicion is very important for early diagnosis and to prevent serious
      consequences.

PMID- 21189931
TI  - Electrocardiography as an early cardiac screening test in children with
      mitochondrial disease.
AB  - PURPOSE: To evaluate myocardial conductivity to understand cardiac involvement in
      patients with mitochondrial disease. METHODS: We performed retrospective study on
      fifty-seven nonspecific mitochondrial encephalopathy patients with no clinical
      cardiac manifestations. The patients were diagnosed with mitochondrial
      respiratory chain complex defects through biochemical enzyme assays of muscle
      tissue. We performed standard 12-lead electrocardiography (ECG) on all patients.
      RESULTS: ECG abnormalities were observed in 30 patients (52.6%). Prolongation of
      the QTc interval (>440 ms) was seen in 19 patients (33.3%), widening of the
      corrected QRS interval in 15 (26.3%), and bundle branch block in four (7.0%).
      Atrioventricular block, premature atrial contraction and premature ventricular
      contraction were seen in two patients each (3.5%) and Wolff-Parkinson-White
      syndrome in one patient (1.8%). CONCLUSION: Given this finding, we recommend
      active screening with ECG in patients with mitochondrial disease even in patients
      without obvious cardiac manifestation.

PMID- 21189933
TI  - A case of meningoencephalitis caused by Listeria monocytogenes in a healthy
      child.
AB  - Listeria monocytogenes is a facultative anaerobic, gram-positive bacillus that is
      isolated from the soil, vegetables, and wild or domestic animals. Listeria occurs
      predominantly in the elderly, immunocompromised patients, pregnant women and
      newborns. Infections by this microorganism are rare in healthy infants and
      children. L. monocytogenes may cause meningitis, meningoencephalitis, brain
      abscess, pyogenic arthritis, osteomyelitis, and liver abscesses in children. The
      course of meningoencephalitis by listeria is often severe and even fatal. Acute
      hydrocephalus can develop as a complication and the mortality associated with
      listeriosis is significantly high. We present a case of meningoencephalitis
      caused by L. monocytogenes in a previously healthy 7-year-old girl.

PMID- 21189934
TI  - A childhood case of spinal tuberculosis misdiagnosed as muscular dystrophy.
AB  - Tuberculosis is primarily a pulmonary disease, but extra-pulmonary manifestations
      are not uncommon, especially in children and adolescents. Ten percent of extra
      pulmonary tuberculosis localizes to the bones and joints, and 56% of such cases
      affect the spine. We treated a childhood case of spinal tuberculosis misdiagnosed
      as muscular dystrophy in a patient without specific constitutional symptoms. We
      report this case because the patient had an unusual presentation of spinal
      tuberculosis.

PMID- 21189935
TI  - A case of anemia caused by combined vitamin B12 and iron deficiency manifesting
      as short stature and delayed puberty.
AB  - Anemia caused by vitamin B12 deficiency resulting from inadequate dietary intake
      is rare in children in the modern era because of improvements in nutritional
      status. However, such anemia can be caused by decreased ingestion or impaired
      absorption and/or utilization of vitamin B12. We report the case of an 18-year
      old man with short stature, prepubertal sexual maturation, exertional dyspnea,
      and severe anemia with a hemoglobin level of 3.3 g/dL. He had a history of small
      bowel resection from 50 cm below the Treitz ligament to 5 cm above the ileocecal
      valve necessitated by midgut volvulus in the neonatal period. Laboratory tests
      showed deficiencies of both vitamin B12 and iron. A bone marrow examination
      revealed dyserythropoiesis and low levels of hemosiderin particles, and a
      cytogenetic study disclosed a normal karyotype. After treatment with parenteral
      vitamin B12 and elemental iron, both anemia and growth showed gradual
      improvement. This is a rare case that presented with short stature and delayed
      puberty caused by nutritional deficiency anemia in Korea.

PMID- 21189936
TI  - A case of pyogenic liver abscess in a 10-year-old girl.
AB  - Pyogenic liver abscesses are rare in children. In pediatric patients, altered
      host defences seem to play an important role. However, pyogenic liver abscess
      also occurs in healthy children. We experienced a case of pyogenic liver abscess
      in a healthy immunocompetent 10-year-old-girl. The patient presented two distinct
      abscesses: one subphrenic and the other intrahepatic. The intrahepatic abscess
      resolved with percutaneous drainage and 3 weeks of parenteral antibiotic therapy
      but the subphrenic abscess which could not be drained needed prolonged parenteral
      antibiotic therapy in addition to oral antibiotic therapy. We performed follow-up
      serial CT scan of the abscess cavity to decide on the duration of antibiotic
      therapy. Here we present this case with a brief review of the literature.

PMID- 21189937
TI  - Clinical presentations of critical cardiac defects in the newborn: Decision
      making and initial management.
AB  - The risk of mortality and morbidity of patients with congenital heart defects
      (CHDs) is highest during neonatal period and increases when diagnosis and proper
      management are delayed. Neonates with critical CHDs may present with severe
      cyanosis, respiratory distress, shock, or collapse, all of which are also
      frequent clinical presentations of various respiratory problems or sepsis in the
      newborn. Early diagnosis and stabilization and timely referral to a tertiary
      cardiac center are crucial to improve the outcomes in neonates with CHDs. In this
      review, the clinical presentation of critical and potentially life-threatening
      CHDs is discussed along with brief case reviews to help understand the
      hemodynamics of these defects and ensure proper decision-making in critically ill
      patients.

PMID- 21189938
TI  - Practical stepwise approach to rhythm disturbances in congenital heart diseases.
AB  - Patients with congenital heart diseases (CHD) are confronted with early- and late
      onset complications, such as conduction disorders, arrhythmias, myocardial
      dysfunction, altered coronary flow, and ischemia, throughout their lifetime
      despite successful hemodynamic and/or anatomical correction. Rhythm disturbance
      is a well-known and increasingly frequent cause of morbidity and mortality in
      patients with CHD. Predisposing factors to rhythm disturbances include underlying
      cardiac defects, hemodynamic changes as part of the natural history, surgical
      repair and related scarring, and residual hemodynamic abnormalities. Acquired
      factors such as aging, hypertension, diabetes, obesity, and others may also
      contribute to arrhythmogenesis in CHD. The first step in evaluating arrhythmias
      in CHD is to understand the complex anatomy and to find predisposing factors and
      hemodynamic abnormalities. A practical stepwise approach can lead to diagnosis
      and prompt appropriate interventions. Electrophysiological assessment and
      management should be done with integrated care of the underlying heart defects
      and hemodynamic abnormalities. Catheter ablation and arrhythmia surgery have been
      increasingly applied, showing increasing success rates with technological
      advancement despite complicated arrhythmia circuits in complex anatomy and the
      difficulty of access. Correction of residual hemodynamic abnormalities may be
      critical in the treatment of arrhythmia in patients with CHD.

PMID- 21189939
TI  - Pulmonary hypertension in infants with bronchopulmonary dysplasia.
AB  - An increase in the number of preterm infants and a decrease in the gestational
      age at birth have resulted in an increase in the number of patients with
      significant bronchopulmonary dysplasia (BPD) and secondary pulmonary hypertension
      (PH). PH contributes significantly to the high morbidity and mortality in the BPD
      patients. Therefore, regular monitoring for PH by using echocardiography and B
      type natriuretic peptide (BNP) or N-terminal-proBNP must be conducted in the BPD
      patients with greater than moderate degree to prevent PH and to ensure early
      treatment if PH is present. In the BPD patients with significant PH, multi
      modality treatment, including treatment for correcting an underlying disease,
      oxygen supply, use of diverse selective pulmonary vasodilators (inhaled nitric
      oxide, inhaled prostacyclins, sildenafil, and endothelin-receptor antagonist) and
      other methods, is mandatory.

PMID- 21189940
TI  - Effect of severe neonatal morbidities on long term outcome in extremely low
      birthweight infants.
AB  - PURPOSE: To assess the validity of individual and combined prognostic effects of
      severe bronchopulmonary dysplasia (BPD), brain injury, retinopathy of prematurity
      (ROP), and parenteral nutrition associated cholestasis (PNAC). METHODS: We
      retrospectively analyzed the medical records of 80 extremely low birthweight
      (ELBW) infants admitted to the neonatal intensive care unit (NICU) of the
      Severance Children's Hospital, and who survived to a postmenstrual age of 36
      weeks. We analyzed the relationship between 4 neonatal morbidities (severe BPD,
      severe brain injury, severe ROP, and severe PNAC) and poor outcome. Poor outcome
      indicated death after a postmenstrual age of 36 weeks or survival with
      neurosensory impairment (cerebral palsy, delayed development, hearing loss, or
      blindness) between 18 and 24 months of corrected age. RESULTS: Each neonatal
      morbidity correlated with poor outcome on univariate analysis. Multiple logistic
      regression analysis revealed that the odds ratios (OR) were 4.9 (95% confidence
      interval [CI], 1.0-22.6; P=0.044) for severe BPD, 13.2 (3.0-57.3; P<.001) for
      severe brain injury, 5.3 (1.6-18.1; P=0.007) for severe ROP, and 3.4 (0.5-22.7;
      P=0.215) for severe PNAC. Severe BPD, brain injury, and ROP were significantly
      correlated with poor outcome, but not severe PNAC. By increasing the morbidity
      count, the rate of poor outcome was significantly increased (OR 5.2; 95% CI, 2.2
      11.9; P<.001). In infants free of the above-mentioned morbidities, the rate of
      poor outcome was 9%, while the corresponding rates in infants with 1, 2, and more
      than 3 neonatal morbidities were 46%, 69%, and 100%, respectively. CONCLUSION: In
      ELBW infants 3 common neonatal mornidifies, severe BPD, brain injury and ROP,
      strongly predicts the risk of poor outcome.

PMID- 21189941
TI  - International travel of Korean children and Dengue fever: A single institutional
      analysis.
AB  - PURPOSE: Dengue fever occurs in many popular tourist destinations and is
      increasingly imported by returning travelers in Korea. Since Korea is not an
      endemic country for dengue fever, pediatricians do not usually suspect dengue
      fever in febrile children even with typical presentation and exposure history.
      This study was performed to describe the international travel experiences and
      dengue fever in Korean children. METHODS: Travel histories were collected based
      on questionnaires completed by all patients' guardians who visited the pediatric
      infectious diseases clinic at Samsung Medical Center from January 2008 to
      December 2008. For patients who were suspected of dengue fever, a serological
      test was performed. RESULTS: Five hundred and seventeen children visited the
      pediatric infectious diseases clinic for the first time during this period. About
      30% of patients who responded to the questionnaire (101/339) had experienced
      international travel within the last 2 years. Four patients were diagnosed with
      dengue fever by serological test. CONCLUSION: Increasing numbers of Korean
      children visit dengue endemic areas and they may return home with dengue fever.
      Dengue fever should be suspected in patients who have a travel history to endemic
      areas.

PMID- 21189942
TI  - An 18-year experience of tracheoesophageal fistula and esophageal atresia.
AB  - PURPOSE: To determine the clinical manifestations and outcomes of patients with
      tracheoesophageal fistula (TEF) and esophageal atresia (EA) born at a single
      neonatal intensive care unit. METHODS: A retrospective analysis was conducted for
      97 patients with confirmed TEF and EA who were admitted to the neonatal intensive
      care unit between 1990 and 2007. RESULTS: The rate of prenatal diagnosis was 12%.
      The average gestational age and birth weight were 37(+2) weeks and 2.5+/-0.7 kg,
      respectively. Thirty-one infants were born prematurely (32%). Type C was the most
      common. The mean gap between the proximal and distal esophagus was 2 cm. Esophago
      esophagostomy was performed in 72 patients at a mean age of 4 days after birth;
      gastrostomy or duodenostomy were performed in 8 patients. Forty patients
      exhibited vertebral, anorectal, cardiac, tracheoesophageal, renal, limb (VACTERL)
      association with at least 2 combined anomalies, and cardiac anomaly was the most
      common. The most common post-operative complications were esophageal stricture
      followed by gastroesophageal reflux. Balloon dilatation was performed for 1.3
      times in 26 patients at a mean age of 3 months. The mortality and morbidity rates
      were 24% and 67%, respectively, and the most common cause of death was sepsis.
      The weight of approximately 40% patients was below the 10th percentile at 2 years
      of age. CONCLUSION: Mortality and morbidity rates of patients with TEF and EA are
      high as compared to those of infants with other neonatal surgical diseases.
      Further efforts must be taken to reduce mortality and morbidity and improve
      growth retardation.

PMID- 21189943
TI  - Analysis of reports on orphan lung diseases in Korean children.
AB  - PURPOSE: Orphan lung diseases are defined as lung diseases with a prevalence of 1
      or less in 2,000 individuals. Despite an increase in the numbers of patients with
      such diseases, few studies on Korean children have appeared. To obtain
      epidemiologic and demographic data on these diseases, we systematically reviewed
      reports on pediatric orphan lung diseases in Korea over the last 50 years.
      METHODS: We reviewed 223 articles that have appeared since 1958 on orphan lung
      diseases in Korean children. These articles described a total of 519 patients
      aged between 0 and 18 years. We classified patients by year of publication,
      diagnosis, geographic region, and journal. RESULTS: Of 519 patients, 401 had
      congenital cystic lung diseases and 66 had bronchiolitis obliterans. About 80% of
      patients were described in reports published in three journals, Pediatric Allergy
      and Respiratory Disease (Korea), the Korean Journal of Pediatrics, and the Korean
      Journal of Thoracic and Cardiovascular Surgery, in which papers on 157 (30.2%),
      138 (26.6%), and 111 (21.4%) patients appeared, respectively. The frequency of
      publication of case reports has increased since 1990. Of the 519 patients, 401
      (77.3%) were from Seoul/Gyeonggi-do and 72 (13.9%) from Busan/Gyeongsangnam-do.
      CONCLUSION: The prevalence of pediatric orphan lung disease has increased since
      1990, and some provinces of Korea have a higher incidence of these diseases than
      do others. Studies exploring the incidence of pediatric orphan lung diseases in
      Korea are needed for effective disease management.

PMID- 21189944
TI  - A case of Rubinstein-Taybi Syndrome with a CREB-binding protein gene mutation.
AB  - Rubinstein-Taybi syndrome (RTS) is a congenital disorder characterized by typical
      facial features, broad thumbs and toes, with mental retardation. Additionally,
      tumors, keloids and various congenital anomalies including congenital heart
      defects have been reported in RTS patients. In about 50% of the patients,
      mutations in the CREB binding protein (CREBBP) have been found, which are
      understood to be associated with cell growth and proliferation. Here, we describe
      a typical RTS patient with Arnold-Chiari malformation. A mutation in the CREBBP
      gene, c.4944_4945insC, was identified by mutational analysis.

PMID- 21189945
TI  - A case report of chronic granulomatous disease presenting with aspergillus
      pneumonia in a 2-month old girl.
AB  - Chronic granulomatous disease (CGD) is an uncommon inherited disorder caused by
      mutations in any of the genes encoding subunits of the superoxide-generating
      phagocyte NADPH oxidase system, which is essential for killing catalase producing
      bacteria and fungi, such as Aspergillus species, Staphylococcus aureus, Serratia
      marcescens, Nocardia species and Burkholderia cepacia. In case of a history of
      recurrent or persistent infections, immune deficiency should be investigated.
      Particularly, in the case of uncommon infections such as aspergillosis in early
      life, CGD should be considered. We describe here a case of CGD that presented
      with invasive pulmonary aspergillosis in a 2-month-old girl. We confirmed
      pulmonary aspergillosis noninvasively through a positive result from the culture
      of bronchial alveolar lavage fluid, positive serological test for Aspergillus
      antigen and radiology results. She was successfully treated with Amphotericin B
      and recombinant IFN-gamma initially. Six weeks later after discharge, she was
      readmitted for pneumonia. Since there were infiltrates on the right lower lung,
      which were considered as residual lesions, voriconazole therapy was initiated.
      She showed a favorable response to the treatment and follow-up CT showed
      regression of the pulmonary infiltrates.

PMID- 21189946
TI  - Erratum: ERRATUM: A childhood case of spinal tuberculosis misdiagnosed as
      muscular dystrophy.
AB  - [This corrects the article on p. 657 in vol. 53.].

PMID- 21189947
TI  - Genetics of kidney development: pathogenesis of renal anomalies.
AB  - Congenital anomalies of the kidney and urinary tract (CAKUT) account for more
      than 50% of abdominal masses found in neonates and involve about 0.5% of all
      pregnancies. CAKUT has a major role in renal failure, and increasing evidence
      suggests that certain abnormalities predispose to the development of hypertension
      and cardiovascular disease in adulthood. To understand the pathogenesis of human
      renal anomalies, understanding the development of kidney is important. Diverse
      anomalies of the kidney corresponding to defects at a particular stage of
      development have been documented recently; however, more research is required to
      understand the molecular networks underlying kidney development, and such an
      investigation will provide a clue to the therapeutic intervention for CAKUT.

PMID- 21189949
TI  - Long-term safety of PEG 4000 in children with chronic functional constipation: A
      biochemical perspective.
AB  - PURPOSE: To evaluate the long-term safety of polyethylene glycol (PEG) 4000 in
      children with constipation, particularly the biochemical aspects of safety.
      METHODS: Medical records were evaluated, and 100 children, who had been taking
      PEG 4000 for more than 6 months, and who had been under clinical and biochemical
      monitoring, were enrolled. Ages; 6.11+/-3.12 years, Duration of therapy; 16.93+/
      7.02 months, dose of PEG 4000; 0.72+/-0.21 g/kg/d. RESULTS: None of the children
      complained of clinical adverse effect. The first biochemical test was performed
      at 8.05 months after beginning of PEG 4000. Serum phosphate (SP) value was high
      in 10 children, and leucopenia was noted in one child. The second test was
      performed in 44 children at 7.57 months after the first test. The SP value was
      high in four children, including the three children whose initial SP value was
      high and one new child. Six out of 10 children with high initial SP value became
      normal and one was lost. Hypernatremia was noted in one child. The third test was
      done in 15 children at 7.5 months after the second test. The SP value of the new
      child from the second test was high, but became normal after finishing treatment.
      Two out of 3 children with high SP value at the second test became normal and one
      was lost. The fourth test was done in 2 children few months after the third test.
      All of the results were normal. There were no relation between duration of
      therapy and hyperphosphatemia, or between dose of PEG 4000 and hyperphosphatemia.
      CONCLUSIONS: PEG 4000 is safe for long-term therapy in children with constipation
      with respect to biochemical parameters.

PMID- 21189948
TI  - Renal fibrosis.
AB  - Renal fibrosis, characterized by tubulointerstitial fibrosis and
      glomerulosclerosis, is the final manifestation of chronic kidney disease. Renal
      fibrosis is characterized by an excessive accumulation and deposition of
      extracellular matrix components. This pathologic result usually originates from
      both underlying complicated cellular activities such as epithelial-to-mesenchymal
      transition, fibroblast activation, monocyte/macrophage infiltration, and cellular
      apoptosis and the activation of signaling molecules such as transforming growth
      factor beta and angiotensin II. However, because the pathogenesis of renal
      fibrosis is extremely complicated and our knowledge regarding this condition is
      still limited, further studies are needed.

PMID- 21189950
TI  - Clinical outcome of acute myocarditis in children according to treatment
      modalities.
AB  - PURPOSE: There is currently little evidence to support intravenous immune
      globulin (IVIG) therapy for pediatric myocarditis. The purpose of our
      retrospective study was to assess the effects of IVIG therapy in patients with
      presumed myocarditis on survival and recovery of ventricular function and to
      determine the factors associated with its poor outcome. METHODS: We reviewed all
      consecutive cases of patients with myocarditis with left ventricular dysfunction
      verified by echocardiogram who had visited 3 university hospitals between January
      2000 and September 2009. These patients were divided into 2 groups. Group 1
      consisted of 23 patients (69.6%) who received IVIG alone or IVIG in combination
      with steroids, and group 2 consisted of 10 patients (30.3%) who received neither
      IVIG nor other immunosuppressive agents. Clinical manifestations, laboratory
      results, echocardiographic findings, and outcomes were compared between these 2
      groups. RESULTS: One year after the initial presentation, the difference in the
      probability of survival did not show statistical significance in IVIG-treated
      patients (P=0.607). Of the echocardiographic parameters on admission, a
      shortening fraction of less than 15% was associated with unremitting cardiac
      failure. Furthermore, anemic patients were more likely to have elevated N
      terminal fragment levels of the B-type natriuretic peptide (NT-proBNP) in the
      progressed group (P=0.036). CONCLUSION: There was no difference between the IVIG
      treated patients and the control patients in the degree of recovery of left
      ventricular function and survival. Prospective, randomized, clinical studies are
      needed to elucidate the effects of IVIG treatment during the acute stage of
      myocarditis on ultimate outcomes.

PMID- 21189951
TI  - Effect of p16 on glucocorticoid response in a B-cell lymphoblast cell line.
AB  - PURPOSE: It has been suggested that p16 has a role in glucocorticoid (GC)-related
      apoptosis in leukemic cells, but the exact mechanisms have yet to be clarified.
      We evaluated the relationship between the GC response and p16 expression in a
      lymphoma cell line. METHODS: We used p16 siRNA transfection to construct p16
      inactivated cells by using the B-cell lymphoblast cell line NC-37. We compared
      glucocorticoid receptor (GR) expression, apoptosis, and cell viability between
      control (p16+ NC-37) and p16 siRNA-transfected (p16- NC-37) cells after a single
      dose of dexamethasone (DX). RESULTS: In both groups, there was a significant
      increase in cytoplasmic GR expression, which tended to be higher for p16+ NC-37
      cells than for p16- NC37 cells at all times, and the difference at 18 h was
      significant (P<0.05). Similar patterns of early apoptosis were observed in both
      groups, and late apoptosis occurred at higher levels at 18 h when the GR had
      already been downregulated (P<0.05). Cell viability decreased in both groups but
      the degree of reduction was more severe in p16+ NC-37 cells after 18 h (P<0.05).
      CONCLUSION: These results suggest a relationship between GR expression and cell
      cycle inhibition, in which the absence of p16 leads to reduced cell sensitivity
      to DX.

PMID- 21189952
TI  - Risk factor for pituitary dysfunction in children and adolescents with Rathke's
      cleft cysts.
AB  - PURPOSE: This study evaluated the clinical manifestations of and risk factors for
      pituitary insufficiency in children and adolescents with Rathke's cleft cysts.
      METHODS: Forty-four patients with Rathke's cleft cysts younger than 19 years who
      visited Seoul National University Children's Hospital between January 1995 and
      September 2009 were enrolled. Rathke's cleft cysts were confirmed histologically
      through an operation in 15 patients and by brain magnetic resonance imaging (MRI)
      in 29 patients. The clinical, hormonal, and imaging features were reviewed
      retrospectively. RESULTS: THE CLINICAL PRESENTATION OF SYMPTOMATIC PATIENTS WAS
      AS FOLLOWS: headache (65%), endocrinopathy (61%), and visual disturbance (19%).
      Endocrinopathy included central precocious puberty (18%), diabetes insipidus
      (14%), general weakness (11%), and decreased growth velocity (7%). After surgery,
      hyperprolactinemia resolved in all patients, but growth hormone insufficiency,
      hypothyroidism, and diabetes insipidus did not improve. Pituitary insufficiency
      except gonadotropin abnormality correlated significantly with severe headache,
      visual disturbance, general weakness, and cystic size. Suprasellar extension of
      cysts and high signals in the T2-weighted image on brain MRI were related to
      hypothyroidism, hypocortisolism, and diabetes insipidus. Multivariable linear
      regression analysis showed that only general weakness was a risk factor for
      pituitary insufficiency (R(2)=0.549). CONCLUSION: General weakness is a risk
      factor for pituitary insufficiency in patients with Rathke's cleft cysts. When a
      patient with a Rathke's cleft cyst complains of general weakness, the clinician
      should evaluate pituitary function and consider surgical treatment.

PMID- 21189953
TI  - A case of regression of atypical dense deposit disease without C3 deposition in a
      child.
AB  - Dense deposit disease (DDD) is a rare disorder characterized by the deposition of
      abnormal electron-dense material within the glomerular basement membrane of the
      kidneys. The diagnosis is made in most patients between 5 and 15 years of age,
      and within 10 years, approximately half of the affected patients progress to end
      stage renal disease. We report a rare case of regressive DDD without C3
      deposition after steroid therapy in an 11-year-old boy. The patient presented
      with edema, gross hematuria, and nephrotic-range proteinuria. Laboratory testing
      revealed a serum creatinine level of 1.17 mg/dL, albumin level of 2.3 g/dL, and
      serum C3 level of 125 mg/dL (range 90-180 mg/dL). The results of the renal biopsy
      were consistent with DDD without C3 deposition. After 6 weeks of steroid therapy,
      the nephrotic syndrome completely resolved. The follow-up renal biopsy showed a
      significant reduction in mesangial proliferation and disappearance of electron
      dense deposits in the GBM.

PMID- 21189954
TI  - Secondary renal amyloidosis in a 13-year-old girl with bronchiectasis.
AB  - A 13-year-old girl was diagnosed with non-cystic fibrosis (CF)-related multifocal
      bronchiectasis accompanied by nephrotic-range proteinuria of unknown cause. On
      renal biopsy, there were many segmental homogeneous deposits of amyloid tissue
      with positive Congo red staining in the glomeruli and interstitium. On electron
      microscopy, relatively straight, non-branching, randomly arranged amyloid fibrils
      were showed in the mesangium of the glomeruli. These fibrils were approximately
      10 nm in diameter, compatible with secondary amyloidosis. Her level of serum
      amyloid A was remarkably elevated. To our knowledge, this girl is the first case
      of secondary renal amyloidosis induced by bronchiectasis in Korean children.

PMID- 21189955
TI  - A case of Pfeiffer syndrome with c833_834GC>TG (Cys278Leu) mutation in the FGFR2
      gene.
AB  - Pfeiffer syndrome is a rare autosomal dominant disorder characterized by coronal
      craniosynostosis, brachycephaly, mid-facial hypoplasia, and broad and deviated
      thumbs and great toes. Pfeiffer syndrome occurs in approximately 1:100,000 live
      births. Clinical manifestations and molecular genetic testing are important to
      confirm the diagnosis. Mutations of the fibroblast growth factor receptor 1
      (FGFR1) gene or FGFR2 gene can cause Pfeiffer syndrome. Here, we describe a case
      of Pfeiffer syndrome with a novel c833_834GC>TG mutation (encoding Cys278Leu) in
      the FGFR2 gene associated with a coccygeal anomaly, which is rare in Pfeiffer
      syndrome.

PMID- 21189956
TI  - Obstructive sleep apnea syndrome in children: Epidemiology, pathophysiology,
      diagnosis and sequelae.
AB  - The prevalence of pediatric obstructive sleep apnea syndrome (OSAS) is
      approximately 3% in children. Adenotonsillar hypertrophy is the most common cause
      of OSAS in children, and obesity, hypotonic neuromuscular diseases, and
      craniofacial anomalies are other major risk factors. Snoring is the most common
      presenting complaint in children with OSAS, but the clinical presentation varies
      according to age. Agitated sleep with frequent postural changes, excessive
      sweating, or abnormal sleep positions such as hyperextension of neck or abnormal
      prone position may suggest a sleep-disordered breathing. Night terror,
      sleepwalking, and enuresis are frequently associated, during slow-wave sleep,
      with sleep-disordered breathing. Excessive daytime sleepiness becomes apparent in
      older children, whereas hyperactivity or inattention is usually predominant in
      younger children. Morning headache and poor appetite may also be present. As the
      cortical arousal threshold is higher in children, arousals are not easily
      developed and their sleep architectures are usually more conserved than those of
      adults. Untreated OSAS in children may result in various problems such as
      cognitive deficits, attention deficit/hyperactivity disorder, poor academic
      achievement, and emotional instability. Mild pulmonary hypertension is not
      uncommon. Rarely, cardiovascular complications such as cor pulmonale, heart
      failure, and systemic hypertension may develop in untreated cases. Failure to
      thrive and delayed development are serious problems in younger children with
      OSAS. Diagnosis of pediatric OSAS should be based on snoring, relevant history of
      sleep disruption, findings of any narrow or collapsible portions of upper airway,
      and confirmed by polysomnography. Early diagnosis of pediatric OSAS is critical
      to prevent complications with appropriate interventions.

PMID- 21189957
TI  - Treatment of obstructive sleep apnea in children.
AB  - Obstructive sleep apnea (OSA) in children is a frequent disease for which optimal
      diagnostic methods are still being defined. Treatment of OSA in children should
      include providing space, improving craniofacial growth, resolving all symptoms,
      and preventing the development of the disease in the adult years.
      Adenotonsillectomy (T&A) has been the treatment of choice and thought to solve
      young patient's OSA problem, which is not the case for most adults. Recent
      reports showed success rates that vary from 27.2% to 82.9%. Children snoring
      regularly generally have a narrow maxilla compared to children who do not snore.
      The impairment of nasal breathing with increased nasal resistance has a well
      documented negative impact on early childhood maxilla-mandibular development,
      making the upper airway smaller and might lead to adult OSA. Surgery in young
      children should be performed as early as possible to prevent the resulting
      morphologic changes and neurobehavioral, cardiovascular, endocrine, and metabolic
      complications. Close postoperative follow-up to monitor for residual disease is
      equally important. As the proportion of obese children has been increasing
      recently, parents should be informed about the weight gain after T&A.
      Multidisciplinary evaluation of the anatomic abnormalities in children with OSA
      leads to better overall treatment outcome.

PMID- 21189958
TI  - Multiple births conceived by assisted reproductive technology in Korea.
AB  - PURPOSE: The recent trends of multiple births (MBs) conceived by assisted
      reproductive technology (ART) in Korea were analyzed as well as the relationship
      with maternal age, especially advanced maternal age. METHODS: Data were obtained
      from the Korean Statistical Information Service and annual ART reports from the
      ART committee of the Korean Society of Obstetrics and Gynecology. RESULTS: MBs
      increased from the early 1990s; there was a 275% increase by 2008. The number of
      total live births was 448,153 and MBs accounted for 10,767; the MB rate was 24.0%
      in 2006. Among 2,326 deliveries conceived by ART, multiple deliveries accounted
      for 786 (33.8%). The total number of live births with ART was 3,125 and 1,585
      (50.7%) of them were MBs. During 2006, 14.7% of the entire MBs in Korea were
      associated with ART. The proportion of women of advanced maternal age was much
      higher in the ART group than in the total live birth group. CONCLUSION: MBs in
      women of advanced maternal age have been increasing in Korea with the use of ART.
      The results of this study showed that ART was a significant factor associated
      with the increase in MBs in Korea.

PMID- 21189959
TI  - Clinical characteristics of children with 2009 pandemic influenza A (H1N1)
      admitted in a single institution.
AB  - PURPOSE: This study aims to investigate the clinical characteristics of children
      diagnosed with the novel influenza A (H1N1) in the winter of 2009 at a single
      medical institution. METHODS: Out of 545 confirmed cases of influenza A (H1N1) in
      children, using the real time RT-PCR method at Kosin University Gospel Hospital
      from September to December of 2009, 149 patients and their medical records were
      reviewed in terms of symptoms, laboratory findings, complications and
      transmission within a family. RESULTS: Median age of subjects was 7 years (range:
      2 months-18 years). New cases increased rapidly from September to reach a peak in
      November, then declined rapidly. Most frequently observed symptoms were fever
      (96.7%), cough (73.2%), rhinorrhea (36.9%) and sore throat (31.5%). Average body
      temperatures on the 1st, 2nd and 3rd hospital day were 38.75+/-0.65C, 38.08+/
      0.87C and 37.51+/-0.76C, respectively. Complete blood counts and biochemical
      tests performed on the first admission day showed within the reference values in
      most cases. Of the 82 patients with simple chest radiography, 18 (22%) had
      pneumonic lesions; multi-focal bronchopneumonia in eleven, single or multi
      segmental lobar pneumonia in five, and diffuse interstitial pneumonia in two
      patients. All of the 149 patients improved from their symptoms and discharged
      within 9 days of admission without any late complication. CONCLUSION: Children
      with 2009 pandemic influenza A (H1N1) at our single institution displayed
      nonspecific symptoms and laboratory findings, resembling those of common viral
      respiratory illnesses, and did not appear to develop more severe disease.

PMID- 21189960
TI  - Prevalence and risk factors of the metabolic syndrome in young adults with
      childhood-onset hypopituitary growth hormone deficiency.
AB  - PURPOSE: This study evaluated the prevalence of the metabolic syndrome (MetS) and
      risk factors for metabolic derangement in young adults with childhood-onset
      hypopituitary growth hormone deficiency (ACOHGHD). METHODS: Thirty patients with
      ACOHGHD who were treated with hormone-replacement therapy, aged 18 to 29 years,
      who visited the Seoul National University Children's Hospital between September
      2009 and February 2010 were enrolled. Height, weight, waist circumference, hip
      circumference, and blood pressure were measured, and the clinical and hormonal
      features were reviewed retrospectively. We evaluated measures of metabolic
      derangement in the enrolled patients and in the data of healthy adults aged 20 to
      29 years taken from the 2005 Korean National Health and Nutrition Examination
      Survey (KNHANES) as part of the National Cholesterol Education Program-the Adult
      Treatment Panel III. RESULTS: Compared with the KNHANES participants, patients
      with ACOHGHD had significantly large waist circumference (men and women), high
      systolic blood pressure (BP) (women) and diastolic BP (men), and high serum
      triglyceride levels (women). The duration of illness correlated significantly
      with central obesity (r(2)=0.546, P=0.003). The prevalence of MetS was 10% in
      patients with ACOHGHD and 2.3% in KNHANES participants. The prevalence of central
      obesity and MetS was higher in patients with ACOHGHD than in KNHANES participants
      (P<0.001 and P=0.042, respectively). CONCLUSION: Abdominal obesity correlated
      with the duration of illness in patients with ACOHGHD. Waist circumference should
      be measured in the clinic to prevent MetS, particularly in patients with a long
      history of ACOHGHD, regardless of age or sex.

PMID- 21189961
TI  - The neuroprotective effect of recombinant human erythropoietin via an
      antiapoptotic mechanism on hypoxic-ischemic brain injury in neonatal rats.
AB  - PURPOSE: The neuroprotective effects of erythropoietin (EPO) have been recently
      shown in many animal models of brain injury, including hypoxic-ischemic (HI)
      encephalopathy, trauma, and excitotoxicity; however, limited data are available
      for such effects during the neonatal periods. Therefore, we investigated whether
      recombinant human EPO (rHuEPO) can protect against perinatal HI brain injury via
      an antiapoptotic mechanism. METHODS: The left carotid artery was ligated in 7-day
      old Sprague-Dawley (SD) rat pups (in vivo model). The animals were divided into 6
      groups: normoxia control (NC), normoxia sham-operated (NS), hypoxia only (H),
      hypoxia+vehicle (HV), hypoxia+rHuEPO before a hypoxic insult (HE-B), and
      hypoxia+rHuEPO after a hypoxic insult (HE-A). Embryonic cortical neuronal cell
      culture of SD rats at 18 days gestation (in vitro model) was performed. The
      cultured cells were divided into 5 groups: normoxia (N), hypoxia (H), and 1, 10,
      and 100 IU/mL rHuEPO-treated groups. RESULTS: In the in vivo model, Bcl-2
      expressions in the H and HV groups were lower than those in the NC and NS groups,
      whereas those in the HE-A and HE-B groups were greater than those of the H and HV
      groups. The expressions of Bax and caspase-3 and the ratio of Bax/Bcl-2 were in
      contrast to those of Bcl-2. In the in vitro model, the patterns of Bcl-2, Bax,
      and caspase-3 expression and Bax/Bcl-2 ratio were similar to the results obtained
      in the in vivo model. CONCLUSION: rHuEPO exerts neuroprotective effect against
      perinatal HI brain injury via an antiapoptotic mechanism.

PMID- 21189962
TI  - An atypical phenotype of hypokalemic periodic paralysis caused by a mutation in
      the sodium channel gene SCN4A.
AB  - Familial hypokalemic periodic paralysis is an autosomal-dominant channelopathy
      characterized by episodic muscle weakness with hypokalemia. The respiratory and
      cardiac muscles typically remain unaffected, but we report an atypical case of a
      family with hypokalemic periodic paralysis in which the affected members
      presented with frequent respiratory insufficiency during severe attacks.
      Molecular analysis revealed a heterozygous c.664 C>T transition in the sodium
      channel gene SCN4A, leading to an Arg222Trp mutation in the channel protein. The
      patients described here presented unusual clinical characteristics that included
      a severe respiratory phenotype, an incomplete penetrance in female carriers, and
      a different response to medications.

PMID- 21189963
TI  - A case of intracranial hemorrhage in a neonate with congenital factor VII
      deficiency.
AB  - Congenital factor VII deficiency is a rare autosomal-recessive bleeding disorder.
      Bleeding manifestations and clinical findings vary widely, ranging from
      asymptomatic subjects to patients with hemorrhages that may cause significant
      handicaps. Treatment has traditionally involved factor VII(FVII) replacement
      therapy using fresh frozen plasma, prothrombin complex concentrates or plasma
      derived FVII concentrates. Recombinant activated FVII (NovoSeven(r)) is currently
      considered the first-line treatment for replacement therapy of FVII deficiency.
      Here we present a case of severe intracerebral and intraventricular hemorrhage in
      a neonate with congenital FVII deficiency.

PMID- 21189964
TI  - Bloody nipple discharge in an infant.
AB  - Although milky nipple discharge appears frequently in infants, bloody nipple
      discharge is a very rare finding. We experienced a 4-month-old, breast-fed infant
      who showed bilateral bloody nipple discharge with no signs of infection,
      engorgement, or hypertrophy. The infant's hormonal examination and coagulation
      tests were normal, and an ultrasound examination revealed mammary duct ectasia.
      The symptoms resolved spontaneously within 6 weeks without any specific
      treatment, except that we advised the mother to refrain from taking herbal
      medicine. Since no such case has been previously reported in Korea, we present
      this case with a brief review of the literature.

PMID- 21189965
TI  - General considerations and updates in pediatric gastrointestinal diagnostic
      endoscopy.
AB  - Gastrointestinal and colonic endoscopic examinations have been performed in
      pediatric patients in Korea for 3 decades. Endoscopic procedures are complex and
      may be unsafe if special concerns are not considered. Many things have to be kept
      in mind before, during, and after the procedure. Gastrointestinal endoscopy is
      one of the most frequently performed procedure in children nowadays, Since the
      dimension size of the endoscopy was modified for pediatric patients 15 years ago,
      endoscopic procedures are almost performed routinely in pediatric
      gastrointestinal patients. The smaller size of the scope let the physicians
      approach the diagnostic and therapeutic endoscopic procedures. But this is an
      invasive procedure, so the procedure itself may provoke an emergence state. The
      procedure-related complications can more easily occur in pediatric patients.
      Sedation-related or procedure-related respiratory, cardiovascular complications
      are mostly important and critical in the care. The endoscopists are required to
      consider diverse aspects of the procedure - patient preparation, indications and
      contraindications, infection controls, sedation methods, sedative medicines and
      the side effects of each medicine, monitoring during and after the procedure, and
      complications related with the procedure and medicines - to perform the procedure
      successfully and safely. This article presents some important guidelines and
      recommendations for gastrointestinal endoscopy through literature review.

PMID- 21189966
TI  - Role of colonoscopy in the diagnosis and treatment of pediatric lower
      gastrointestinal disorders.
AB  - The safety and effectiveness of colonoscopy in the investigation of lower
      gastrointestinal tract pathology in children has been established for more than 2
      decades in Korea. Skill and experience have since advanced to the point that both
      diagnostic and therapeutic colonoscopy are now routinely performed by most
      pediatric gastroenterologists. Pediatric colonoscopy differs significantly from
      its adult parallels in nearly every aspect including patient and parent
      management and preparation, selection criteria for sedation and general
      anesthetic, bowel preparation, expected diagnoses, instrument selection,
      imperative for terminal ileal intubation, and requirement for biopsies from
      macroscopically normal mucosa. Investigation of inflammatory bowel disease,
      whether for diagnosis or follow-up evaluation, and suspected colonic polyps are
      the most common indication for pediatric colonoscopy. The child who presents with
      signs and symptoms of lower gastrointestinal disorder should undergo colonoscopy
      with biopsy to make the diagnosis, as well as to help determine the appropriate
      therapy. This review introduces practical information on pediatric colonoscopy,
      the author's experiences, and the role of colonoscopic examination in the
      diagnosis and treatment of pediatric lower gastrointestinal disorders.

PMID- 21189967
TI  - Change in the treatment strategy for pediatric Crohn's disease.
AB  - Crohn's disease is characterized by chronic inflammation involving any portion of
      the gastrointestinal tract. Treating Crohn's disease is a major challenge for
      clinicians, as no curative therapy currently exists. Pediatric Crohn's disease is
      characterized by frequent relapses, a wide extent of disease, a high prevalence
      of extraintestinal manifestations, and a severe clinical course. The classic
      therapeutic approach is known as the 'step-up' strategy, and follows a
      progressive course of treatment intensification as disease severity increases.
      Although this approach is usually effective for symptom control, many patients
      become either resistant to or dependent on corticosteroids. The efficacy of
      infliximab suggests that, rather than a progressive course of treatment, early
      intense induction may reduce complications associated with conventional treatment
      and improve quality of life. Intensive early therapy with infliximab is known as
      the 'top-down' strategy. Such therapy offers the potential for altering the
      natural history of Crohn's disease, and is changing treatment paradigms. However,
      the relatively new concept of an early aggressive or 'top-down' treatment
      approach is not yet widely accepted, especially in pediatric patients. The
      results of our current study demonstrate that early and intensive treatment of
      pediatric Crohn's disease patients with infliximab, at initial diagnosis, was
      more effective for maintaining remission and reducing flares.

PMID- 21189968
TI  - Korean speech sound development in children from bilingual Japanese-Korean
      environments.
AB  - PURPOSE: This study investigates Korean speech sound development, including
      articulatory error patterns, among the Japanese-Korean children whose mothers are
      Japanese immigrants to Korea. METHODS: The subjects were 28 Japanese-Korean
      children with normal development born to Japanese women immigrants who lived in
      Jeonbuk province, Korea. They were assessed through Computerized Speech Lab 4500.
      The control group consisted of 15 Korean children who lived in the same area.
      RESULTS: The values of the voice onset time of consonants /p(h)/, /t/, /t(h)/,
      and /k(*)/ among the children were prolonged. The children replaced the lenis
      sounds with aspirated or fortis sounds rather than replacing the fortis sounds
      with lenis or aspirated sounds, which are typical among Japanese immigrants. The
      children showed numerous articulatory errors for /c/ and /l/ sounds (similar to
      Koreans) rather than errors on /p/ sounds, which are more frequent among Japanese
      immigrants. The vowel formants of the children showed a significantly prolonged
      vowel /o/ as compared to that of Korean children (P<0.05). The Japanese
      immigrants and their children showed a similar substitution /n/ for /?/ [Japanese
      immigrants (62.5%) vs Japanese-Korean children (14.3%)], which is rarely seen
      among Koreans. CONCLUSION: The findings suggest that Korean speech sound
      development among Japanese-Korean children is influenced not only by the Korean
      language environment but also by their maternal language. Therefore, appropriate
      language education programs may be warranted not only or immigrant women but also
      for their children.

PMID- 21189969
TI  - Microalbuminuria in children with urinary tract infection.
AB  - PURPOSE: Microalbuminuria is defined as increased urinary albumin excretion (30
      300 mg/day) or microalbumin/creatinine ratio (30-300 mg/g) in a spot urine
      sample. Although microalbuminuria is a predictor of clinical nephropathy and
      cardiomyopathy, few studies have investigated microalbuminuria in children with
      urinary tract infection (UTI). METHODS: Therefore, we compared the spot urine
      microalbumin/creatinine ratio in pediatric UTI patients with that of control
      subjects. We investigated the correlation between the ratio in children with UTI
      and age, height, weight, blood pressure, glomerular filtration rate (GFR),
      hematuria, vesicoureteral reflux, renal parenchymal defect, and renal scar, and
      its predictability for UTI complications. RESULTS: We studied 66 patients (42
      boys, 24 girls) and 52 healthy children (24 boys, 28 girls). The mean
      microalbumin/creatinine ratio in UTI patients was statistically significantly
      increased compared to the control group (340.04+/-321.36 mg/g (38.47+/-36.35
      mg/mmol) in patient group vs. 225.68+/-154.61 mg/g (25.53+/-17.49 mg/mmol) in
      control group, P=0.0141). The mean value of spot urine microalbumin/creatinine
      ratio (384.70+/-342.22 mg/g (43.47+/-37.67 mg/mmol) in patient group vs. 264.92+/
      158.13 mg/g (29.94+/-17.86 mg/mmol) in control group, P=0.0341) in 1-23 months
      age patient group showed statistically significant increase compared to control
      group. Microalbumin/creatinine ratio showed negative correlation to age (r=-0.29,
      P=0.0167), body surface area (BSA) (r=-0.29, P=0.0173) and GFR (r=-0.26,
      P=0.0343). The presence of hematuria (P=0.0169) was found to be correlated.
      CONCLUSION: The spot urine microalbumin/creatinine ratio in children with UTI was
      significantly greater than that in normal children, and it was positively
      correlated with GFR. This ratio is a potential prescreening and prognostic marker
      in UTI patients. Further studies are required to validate the predictability of
      microalbuminuria in pediatric UTI patients.

PMID- 21189970
TI  - Effects of human growth hormone on gonadotropin-releasing hormone neurons in
      mice.
AB  - PURPOSE: Recombinant human growth hormone (rhGH) has been widely used to treat
      short stature. However, there are some concerns that growth hormone treatment may
      induce skeletal maturation and early onset of puberty. In this study, we
      investigated whether rhGH can directly affect the neuronal activities of of
      gonadotropin-releasing hormone (GnRH). METHODS: We performed brain slice
      gramicidin-perforated current clamp recording to examine the direct membrane
      effects of rhGH on GnRH neurons, and a whole-cell voltage-clamp recording to
      examine the effects of rhGH on spontaneous postsynaptic events and holding
      currents in immature (postnatal days 13-21) and adult (postnatal days 42-73)
      mice. RESULTS: In immature mice, all 5 GnRH neurons recorded in gramicidin
      perforated current clamp mode showed no membrane potential changes on application
      of rhGH (0.4, 1 ug/mL). In adult GnRH neurons, 7 (78%) of 9 neurons tested showed
      no response to rhGH (0.2-1 ug/mL) and 2 neurons showed slight depolarization. In
      9 (90%) of 10 immature neurons tested, rhGH did not induce any membrane holding
      current changes or spontaneous postsynaptic currents (sPSCs). There was no change
      in sPSCs and holding current in 4 of 5 adult GnRH neurons. CONCLUSION: These
      findings demonstrate that rhGH does not directly affect the GnRH neuronal
      activities in our experimental model.

PMID- 21189971
TI  - Testicular torsion in the inguinal region in an extremely low birth weight
      infant.
AB  - Testicular torsion is rare in newborn infants. However, its frequency has
      increased, most of which are reported in full-term infants. We diagnosed and
      treated testicular torsion in an extremely low birth weight infant (ELBWI). A 2*2
      cm red mass was palpable in the left groin of a 24-week-old, 745 g, male newborn
      at 23 days of age. Left testicular torsion was diagnosed, and emergent orchiopexy
      was performed. Careful physical examination is needed in cases suspicious of
      testicular torsion in ELBWIs with cryptorchidism. Moreover, early diagnosis and
      emergent exploration are necessary to prevent complications such as the risk of
      anorchia.

PMID- 21189972
TI  - A case of Kawasaki disease with coexistence of a parapharyngeal abscess requiring
      incision and drainage.
AB  - Kawasaki disease (KD) causes multisystemic vasculitis but infrequently manifests
      with deep neck infections, such as a peritonsillar abscess, peritonsillar or deep
      neck cellulitis, suppurative parapharyngeal infection, or retropharyngeal
      abscess. As its etiology is still unknown, the diagnosis is usually made based on
      typical symptoms. The differential diagnosis between KD and deep neck infections
      is important, considering the variable head and neck manifestations of KD. There
      are several reports on KD patients who were initially diagnosed with
      retropharyngeal abscess on on computed tomography scans (CT). However, the
      previously reported cases did not have abscess or fluid collection on
      retropharyngeal aspiration. Therefore, false-positive neck CT scans have been
      obtained, until recently. In this case, suspected neck abscess in patients with
      KD unresponsive to intravenous immunoglobulin could signal the possible
      coexistence of suppurative cervical lymphadenitis.

PMID- 21189973
TI  - Transient splenial lesion of the corpus callosum in a case of benign convulsion
      associated with rotaviral gastroenteritis.
AB  - Transient magnetic resonance (MR) signal changes in the splenium of the corpus
      callosum (SCC) arise from many different conditions, including encephalopathy or
      encephalitis caused by infection, seizures, metabolic derangements, and asphyxia.
      Few case reports exist on reversible SCC lesions associated with rotavirus
      infection. A benign convulsion with mild gastroenteritis (CwG) is frequently
      associated with rotaviral infections. This entity is characterized by normal
      laboratory findings, electroencephalogram, neuroimaging, and good prognosis. We
      report a case of a 2.5-year-old Korean girl with rotavirus-associated CwG
      demonstrating a reversible SCC lesion on diffusion-weighted MR images. She
      developed 2 episodes of brief generalized tonic-clonic seizure with mild acute
      gastroenteritis without any other neurologic abnormality. Stool test for
      rotavirus antigen was positive. Brain MRI done on the day of admission showed a
      linear high signal intensity and decreased apparent diffusion coefficient values
      on the SCC. The lesion completely disappeared on follow-up MRI 6 days later. The
      patient fully recovered without any sequelae.

PMID- 21189974
TI  - Multimodal neuroimaging in presurgical evaluation of childhood epilepsy.
AB  - In pre-surgical evaluation of pediatric epilepsy, the combined use of multiple
      imaging modalities for precise localization of the epileptogenic focus is a
      worthwhile endeavor. Advanced neuroimaging by high field Magnetic resonance
      imaging (MRI), diffusion tensor images, and MR spectroscopy have the potential to
      identify subtle lesions. (18)F-FDG positron emission tomography and single photon
      emission tomography provide visualization of metabolic alterations of the brain
      in the ictal and interictal states. These techniques may have localizing value
      for patients which exhibit normal MRI scans. Functional MRI is helpful for non
      invasively identifying areas of eloquent cortex. These advances are improving our
      ability to noninvasively detect epileptogenic foci which have gone undetected in
      the past and whose accurate localization is crucial for a favorable outcome
      following surgical resection.

PMID- 21189975
TI  - Disease-specific pluripotent stem cells.
AB  - Induced pluripotent stem (iPS) cells are generated by epigenetic reprogramming of
      somatic cells through the exogenous expression of transcription factors.
      Recently, the generation of iPS cells from patients with a variety of genetic
      diseases was found to likely have a major impact on regenerative medicine,
      because these cells self-renew indefinitely in culture while retaining the
      capacity to differentiate into any cell type in the body, thereby enabling
      disease investigation and drug development. This review focuses on the current
      state of iPS cell technology and discusses the potential applications of these
      cells for disease modeling; drug discovery; and eventually, cell replacement
      therapy.

PMID- 21189976
TI  - The effect of sucrose on infants during a painful procedure.
AB  - PURPOSE: The purpose of this study was to test the efficacy of treating the pain
      among newborn infants associated with a medical procedure with sucrose with
      regard to overall physiological and behavioral stability. METHODS: 103 newborn
      infants were enrolled in this study. The control group (n=63) did not receive any
      treatment. The experimental group (n=40) received 2 mL of 24% sucrose solution
      two minutes before a routine heel stick. The pain was assessed by measurements of
      physiological changes [e.g. pulse rate, oxygen saturation, salivary cortisol
      (hydrocortisone)] and behavioral changes [e.g. crying time, and the neonatal
      infant pain scale (NIPS) for neonates]. RESULTS: There were no differences among
      the groups with respect to physiological changes associated with the pain from
      the procedure. However, there were significant group differences in behavioral
      changes to the pain. In the control group, the median crying time was 13 seconds,
      while in the experimental group, the median crying time was 3.5 seconds (P=.000).
      In the control group the median NIPS score was 4, while in the experimental group
      the median NIPS score was 2 (P=.000). CONCLUSIONS: These findings suggest that
      sucrose can be an effective method for the management of stress responses in
      infants with regard to behavior. However, this treatment had no significant
      physiological effects.

PMID- 21189977
TI  - Increased B cell-activating factor (BAFF) level in the sputum of children with
      asthma.
AB  - PURPOSE: B cell-activating factor (BAFF) is a tumor-necrosis factor (TNF)
      superfamily member best known for its role in the survival and maturation of B
      cells. BAFF activity is observed in naive cells as well as in effector/memory T
      cells. We aimed to explore whether BAFF in sputum is expressed at elevated levels
      in asthmatic airways and associated with eosinophilic inflammation, pulmonary
      function, and bronchial hyperresponsiveness in children. METHODS: One hundred and
      fifty-four asthmatic children and 98 healthy children were enrolled in the study.
      Sputum supernatants were collected and sputum BAFF and eosinophil cationic
      protein (ECP) levels were measured. We performed pulmonary function tests and
      methacholine challenge tests, while measuring total eosinophil count, total serum
      IgE, and serum ECP in all subjects. RESULTS: Asthmatic children had significantly
      higher levels of BAFF in induced sputum [26.50 (10.50-100.27) pg/mL] compared to
      healthy children [18.32 (7.68-44.63) pg/mL; P=0.011]. Sputum BAFF positively
      correlated with sputum eosinophils (gamma=0.406, P<0.001) and sputum ECP
      (gamma=0.789, P<0.001). Significant negative correlations were found between
      sputum BAFF and FEV1 (gamma=-0.291, P<0.001) or post-bronchodilator FEV1 (gamma=
      0.334, P<0.001), whereas nonsignificant correlations were found between sputum
      BAFF and bronchial hyperresponsiveness, serum eosinophil count, and serum ECP.
      CONCLUSION: These findings suggest that BAFF may play a role in childhood asthma,
      and BAFF levels in sputum could be a supportive marker that represents airway
      inflammation, especially eosinophilic inflammation.

PMID- 21189978
TI  - Needle aspiration as therapeutic management for suppurative cervical
      lymphadenitis in children.
AB  - PURPOSE: This study aimed to evaluate the usefulness of the needle aspiration
      alternative to open surgical drainage of children with suppurative cervical
      lymphadenitis requiring surgical drainage. METHODS: From January 1998 to June
      2008, we retrospectively reviewed 38 children treated with needle aspiration as
      management with suppurative cervical lymphadenitis instead of open surgical
      drainage. RESULTS: All 38 children underwent only 1 puncture. Two patients (5.2%)
      out of 38 patients experienced reformation of an abscess and all recovered
      completely after re-treatment with antibiotics. Minor complications were detected
      in 2 patients (5.2%). One complication originated from remnant necrotic tissue
      and the other involved formation of a small scar in two patients, which resolved
      spontaneously. There were no major complications. CONCLUSION: Needle aspiration
      can be a simple, safe, and effective alternative procedure to open surgical
      drainage of children with suppurative cervical lymphadenitis requiring surgical
      drainage.

PMID- 21189979
TI  - Successful treatment by exchange transfusion of a young infant with sodium
      nitroprusside poisoning.
AB  - Although sodium nitroprusside (SNP) is often used in pediatric intensive care
      units, cyanide toxicity can occur after SNP treatment. To treat SNP-induced
      cyanide poisoning, antidotes such as amyl nitrite, sodium nitrite, sodium
      thiosulfate, and hydroxycobalamin should be administered immediately after
      diagnosis. Here, we report the first case of a very young infant whose SNP
      induced cyanide poisoning was successfully treated by exchange transfusion. The
      success of this alternative method may be related to the fact that exchange
      transfusion not only removes the cyanide from the blood but also activates
      detoxification systems by supplying sulfur-rich plasma. Moreover, exchange
      transfusion replaces cyanide-contaminated erythrocytes with fresh erythrocytes,
      thereby improving the blood's oxygen carrying capacity more rapidly than antidote
      therapy. Therefore, we believe that exchange transfusion might be an effective
      therapeutic modality for critical cases of cyanide poisoning.

PMID- 21189980
TI  - A case of Bartter syndrome type I with atypical presentations.
AB  - Bartter syndrome (BS) is an autosomal recessively inherited rare renal tubular
      disorder characterized by hypokalemic metabolic alkalosis and hyperreninemic
      hyperaldosteronism with normal to low blood pressure due to a renal loss of
      sodium. Genetically, BS is classified into 5 subtypes according to the underlying
      genetic defects, and BS is clinically categorized into antenatal BS and classical
      BS according to onset age. BS type I is caused by loss-of-function mutations in
      the SLC12A1 gene and usually manifests as antenatal BS. This report concerns a
      male patient with compound heterozygous missense mutations on SLC12A1 (p.C436Y
      and p.L560P) and atypical clinical and laboratory features. The patient had low
      urinary sodium and chloride levels without definite metabolic alkalosis until the
      age of 32 months, which led to confusion between BS and nephrogenic diabetes
      insipidus (NDI). In addition, the clinical onset of the patient was far beyond
      the neonatal period. Genetic study eventually led to the diagnosis of BS type I.
      The low urinary sodium and chloride concentrations may be caused by secondary
      NDI, and the later onset may suggest the existence of a genotype-phenotype
      correlation.In summary, BS type I may have phenotype variability including low
      urine sodium and chloride levels and later onset. A definitive diagnosis can be
      confirmed by genetic testing.

PMID- 21189981
TI  - A decade of forensic odontology in India.

PMID- 21189982
TI  - Role of a dentist in discrimination of abuse from accident.
AB  - Most physical injuries resulting from abuse or violence are found on the head and
      neck areas that are clearly visible to the dental team during examination. Given
      that dental professionals routinely assess the head, face, and neck of patients,
      they are in a unique position to identify the signs of abuse and neglect.
      Involvement of a dentist in the protection team may be beneficial and can lead to
      early intervention. This article brings to light the importance of questioning
      and physical examination and the role of a dentist in identifying abuse, assault,
      and accident.

PMID- 21189983
TI  - Dental records: An overview.
AB  - Dental records consist of documents related to the history of present illness,
      clinical examination, diagnosis, treatment done, and the prognosis. A thorough
      knowledge of dental records is essential for the practicing dentist, as it not
      only has a forensic application, but also a legal implication with respect to
      insurance and consumerism. This article reviews the importance of dental records
      in forensics.

PMID- 21189984
TI  - Natural dyes versus lysochrome dyes in cheiloscopy: A comparative evaluation.
AB  - Cheiloscopy is the study of lip prints. Lip prints are genotypically determined
      and are unique, and stable. At the site of crime, lip prints can be either
      visible or latent. To develop lip prints for study purpose various chemicals such
      as lysochrome dyes, fluorescent dyes, etc. are available which are very
      expensive. Vermilion (Sindoor used by married Indian women) and indigo dye
      (fabric whitener) are readily available, naturally derived, and cost-effective
      reagents available in India. OBJECTIVE: To compare the efficacy of sudan black,
      vermilion, and indigo in developing visible and latent lip prints made on bone
      china cup, satin fabric, and cotton fabric. MATERIALS AND METHODS: Out of 45
      Volunteers 15 lip prints were made on bone China cup 15 lip prints on Satin
      fabric and 15 on Cotton fabric. Sudan black, vermilion and indigo were applied on
      visible and latent lip prints and graded as good (+,+), fair (+), and poor (-)
      and statistically evaluated. RESULTS: The vermilion and indigo dye gives
      comparable results to that of sudan black for developing visible and latent lip
      prints.

PMID- 21189985
TI  - A comparative analysis of root dentin transparency with known age.
AB  - OBJECTIVE: To correlate dimensions of root transparency and age, and to assess
      whether transparency is reliable for age estimation of unknown. MATERIALS AND
      METHODS: 50 freshly extracted single rooted permanent teeth from 50 different
      individuals (27 males and 23 females) were collected and their ground sections of
      400 MUm were stained with 1% methylene blue. The area of the translucent zone was
      measured by superimposing a transparent graph paper on the ground section under
      stereomicroscope. The length of the translucency was measured by using digital
      vernier caliper. RESULTS: A strong positive correlation between age and
      translucency of dentin was noted. The length rather than the area of the
      translucent zone correlated more with age. CONCLUSION: Translucency of the root
      dentin increases with age and it can be used as a reliable parameter for the age
      estimation.

PMID- 21189986
TI  - Radiographic evaluation of dental age of adults using Kvaal's method.
AB  - INTRODUCTION: It is a well-known fact that the assessment of the dental
      development can be related to an individual's age, but after the age of 21 years
      when the wisdom teeth also complete their development, there arises a need for an
      optimal age estimation procedure. With advancing age, there is a reduction in the
      size of the pulp due to secondary dentin deposition and a measurement of this
      reduction can also be used as a parameter to assess the age of the individuals,
      both in the living and dead. AIMS AND OBJECTIVES: The purpose of the present
      study was to evaluate the feasibility of this approach in the estimation of age
      of adults, using Kvaal's method in the set sample. MATERIALS AND METHODS: The
      material consisted of the digital long-cone intraoral periapical radiographs from
      50 subjects of either sex in the age group of 15-60 years, who were selected
      after evaluation for the set inclusion and exclusion criteria. The pulp width and
      length from radiographs of 6 selected teeth, namely, maxillary central incisor,
      lateral incisor, and second premolar and mandibular lateral incisor, canine, and
      first premolar of either right or left side were measured using the RVG trophy
      software [Trophy(r) Windows is a software program supplied by Trophy Radiologie
      (Trophy Windows Version 5.03, Copyright 1993-2002,Trophy RVG patented by Trophy,
      Chicago)]. In order to compensate for the differences in magnification and
      angulation, various ratios were calculated and the mean of all ratios (M) was
      taken as the first predictor, while the difference between the mean of 2 width
      ratios and the mean of 2 length ratios (W - L) was taken as the second predictor.
      Different regression formulae for all 6 teeth, 3 maxillary teeth, 3 mandibular
      teeth, and each of the individual teeth were derived and the age was assessed.
      The assessed age was then co-related with the actual age of the patient using the
      Student's t test. RESULTS: The results showed that the coefficient of
      determination (R(2)) was the strongest (0.198) for the mandibular first premolar
      indicating that age can be estimated better with this particular tooth. No
      significant difference was observed between the estimated age and the actual age
      for all (P>0.05) except in mandibular lateral incisor and maxillary lateral
      incisor, where a significant difference was observed. CONCLUSION: To conclude,
      the results of the present study suggest the feasibility of Kvaal's method for
      age estimation in the set sample.

PMID- 21189987
TI  - Palatal rugoscopy: Establishing identity.
AB  - Palatal rugae are irregular, asymmetric ridges of the mucous membrane extending
      laterally from the incisive papilla and the anterior part of the palatal raphe.
      The uniqueness and the overall stability of palatal rugae suggest their use for
      forensic identification. OBJECTIVE: The purpose of this study was to compare the
      palatal rugae patterns in 2 different populations in India (Madhya Pradesh and
      Kerala), and furthermore, to assess the predominant pattern if any in the
      selected groups. MATERIALS AND METHODS: 60 maxillary study models (30 from each
      group) were examined in the age group ranging from 17 to 23 years. Palatal rugae
      pattern were examined in both the sexes on right and left sides of the palate for
      the total number (quantitative), length, shape, and predominant direction
      (qualitative). RESULTS: After analyzing the rugae patterns in both the groups and
      between the 2 sides of the palate, the wavy pattern was found to be predominant
      followed by curved, straight, unification, circular, and nonspecific in
      decreasing order in the overall population. CONCLUSION: Straight rugae pattern on
      the right side of the palate in the male subjects was found to be significantly
      predominant in the MP population, whereas wavy shape was predominant in
      Keralites; however, rugae patterns on the right side of the palate in female
      subjects exhibited no significant difference.

PMID- 21189988
TI  - Isolation of epithelial cells from acrylic removable dentures and gender
      identification by amplification of SRY gene using real time PCR.
AB  - This study evaluates the usefulness of acrylic dentures as the source of DNA for
      forensic analysis. Thirty-eight samples (21 males and 17 females) were collected
      and stored for different time periods. The epithelial cells adhered to the
      dentures were retrieved and the genomic DNA was extracted. All the samples
      yielded sufficient amount of DNA for analysis irrespective of the storage time.
      Gender determination was done by amplification of the sex determining region on
      the Y chromosome (SRY) using real-time polymerase chain reaction with 100%
      accuracy, within minimal time. With this study, we conclude that saliva-stained
      acrylic dentures can act as a source of forensic DNA and co-amplification of SRY
      gene with other routine sex typing markers will give unambiguous gender
      identification.

PMID- 21189989
TI  - Effects of high temperature on different restorations in forensic identification:
      Dental samples and mandible.
AB  - INTRODUCTION: The forensic odontologist strives to utilize the charred human
      dentition throughout each stage of dental evaluation, and restorations are as
      unique as fingerprints and their radiographic morphology as well as the types of
      filling materials are often the main feature for identification. The knowledge of
      detecting residual restorative material and composition of unrecovered adjacent
      restoration is a valuable tool-mark in the presumptive identification of the
      dentition of a burned victim. Gold, silver amalgam, silicate restoration, and so
      on, have a different resistance to prolonged high temperature, therefore, the
      identification of burned bodies can be correlated with adequate qualities and
      quantities of the traces. Most of the dental examination relies heavily on the
      presence of the restoration as well as the relationship of one dental structure
      to another. This greatly narrows the research for the final identification that
      is based on postmortem data. AIM: The purpose of this study is to examine the
      resistance of teeth and different restorative materials, and the mandible, to
      variable temperature and duration, for the purpose of identification. MATERIALS
      AND METHODS: The study was conducted on 72 extracted teeth which were divided
      into six goups of 12 teeth each based on the type of restorative material. (Group
      1 - unrestored teeth, group 2 - teeth restored with Zn(3)(PO(4))(2), group 3 -
      with silver amalgam, group 4 with glass ionomer cement, group 5 - Ni-Cr-metal
      crown, group 6 - metal ceramic crown) and two specimens of the mandible. The
      effect of incineration at 400 degrees C (5 mins, 15 mins, 30 mins) and 1100
      degrees C (15 mins) was studied. RESULTS: Damage to the teeth subjected to
      variable temperatures and time can be categorized as intact (no damage), scorched
      (superficially parched and discolored), charred (reduced to carbon by incomplete
      combustion) and incinerated (burned to ashes).

PMID- 21189990
TI  - Re-engineering the mitochondrial genomes in mammalian cells.
AB  - Mitochondria are subcellular organelles composed of two discrete membranes in the
      cytoplasm of eukaryotic cells. They have long been recognized as the generators
      of energy for the cell and also have been known to associate with several
      metabolic pathways that are crucial for cellular function. Mitochondria have
      their own genome, mitochondrial DNA (mtDNA), that is completely separated and
      independent from the much larger nuclear genome, and even have their own system
      for making proteins from the genes in this mtDNA genome. The human mtDNA is a
      small (~16.5 kb) circular DNA and defects in this genome can cause a wide range
      of inherited human diseases. Despite of the significant advances in discovering
      the mtDNA defects, however, there are currently no effective therapies for these
      clinically devastating diseases due to the lack of technology for introducing
      specific modifications into the mitochondrial genomes and for generating accurate
      mtDNA disease models. The ability to engineer the mitochondrial genomes would
      provide a powerful tool to create mutants with which many crucial experiments can
      be performed in the basic mammalian mitochondrial genetic studies as well as in
      the treatment of human mtDNA diseases. In this review we summarize the current
      approaches associated with the correction of mtDNA mutations in cells and
      describe our own efforts for introducing engineered mtDNA constructs into the
      mitochondria of living cells through bacterial conjugation.

PMID- 21189991
TI  - CDH3/P-Cadherin regulates migration of HuCCT1 cholangiocarcinoma cells.
AB  - Intrahepatic cholangiocarcinoma is the second most common subtype of primary
      hepatobilliary cancer. Despite advances in surgical and medical therapy, its
      survival rate remains poor. Compared to hepatocellular carcinoma (HCC), the most
      common liver malignancy, the underlying mechanisms of cholangiocarcinoma
      carcinogenesis are poorly characterized. P-cadherin (CDH3) is a cadherin super
      family member. Although CDH3 is frequently over-expressed in cholangiocarcinoma
      tissues, its roles have never been characterized. To determine the roles of CDH3
      in cholangiocarcinoma, we investigated CDH3 function in HuCCT1 cells using
      specific siRNA. Transfection with CDH3 siRNA did not affect proliferation of
      HuCCT1 cells. However, cell migration and invasion were significantly reduced
      when CDH3 was down-regulated. In addition, expressions of several biomarkers for
      epithelial-mesenchymal transition (EMT) were not changed by CDH3 down-regulation.
      These results suggest that CDH3 regulates cell migration independent of EMT in
      cholangiocarcinoma cells.

PMID- 21189992
TI  - Assessment of experimental saccular aneurysm using selective angiography in
      common carotid artery of rabbits.
AB  - In order to study the treatment of aneurysms, the technique of making
      experimental aneurysms in laboratory animals must be established. In our study,
      to examine the feasibility of making experimental aneurysm and selective
      angiography on the common carotid artery in rabbits and to determine the size of
      experimental aneurysm after surgery, saccular aneurysms were fashioned on the
      right common carotid artery in 17 rabbits using a vein pouch technique. Selective
      angiography of the common carotid artery was performed immediately after surgery,
      and at 1 week, 4 weeks, and 8 weeks after surgery. Also, histological changes in
      the aneurysms were observed. In 16 rabbits with established successful
      experimental aneurysm, no differences were found in diet intake and behavior
      before and after surgery. The patency of the carotid artery was confirmed by
      selective angiography. The average size of the aneurysm immediately after surgery
      was similar to that of 1 week postoperatively in selective angiography, however
      it increased with time at 4weeks and 8 weeks. Histologically, infiltration of
      inflammatory cells and hemorrhage were found at the junction of the carotid
      artery and the vein pouch at 1 week, which disappeared at 4 weeks and 8 weeks.
      This study suggests experimental saccular aneurysm using the vein pouch technique
      might form aneurysms similar to that of the human in its properties such as
      increment of size, and selective angiography might be suitable for assessment of
      experimental aneurysm. Therefore, this animal model may be suitable for
      investigating new treatment methodologies for human aneurysms.

PMID- 21189993
TI  - Effects of hyaluronan on carrageenan-induced synovitis in rat TMJ.
AB  - Nitric oxide is one of many proinflammatory mediators that are involved in
      temporomandibular joint (TMJ) inflammatory disorder and is synthesized by
      inducible nitric oxide synthase (iNOS). iNOS is transcriptionally regulated by
      nuclear factor-kappaB (NF-kappaB) in cases of inflammation, proliferation, and
      apoptosis. It has also been reported that nitric oxide is positively regulated by
      carrageenan and negatively regulated by hyaluronan in the knee joint. The aim of
      this study was to histologically evaluate how inflammation and cell proliferation
      of the synovial membrane are affected by the exogenous administration of
      carrageenan and hyaluronan in the rat TMJ by investigating iNOS, NF-kappaB, and
      anti proliferating cell nuclear antigen (PCNA) immunoreactivity. As results,
      immunoreactive cells to iNOS, NF-kappaB, and PCNA were normally localized only in
      the synovial membrane of wild type TMJs. The numbers of immunoreactive cells were
      extensively larger in the carrageenan-injected synovial membranes exhibiting
      excessive folding, and smaller in the hyaluronan-injected synovial membranes
      showing a few folds. These results indicate that a carrageenan injection induced
      inflammation and cell proliferation especially in the synovial membrane and that
      hyaluronan relieved the inflammation by decreasing inflammatory molecules in the
      synovial membrane.

PMID- 21189994
TI  - Expression of calponin in periglomerular myofibroblasts of rat kidney with
      experimental chronic injuries.
AB  - Our previous research demonstrated that calponin-immunoreactivity was localized
      in myofibroblasts of the periglomerular region of human kidney specimens obtained
      at the time of transplantation from organ recipients. In the present study we
      examined calponin expression in two chronic nephropathy models, puromycin
      aminonucleoside (PAN) nephropathy and subtotal nephrectomy (SNx), to investigate
      the role of calponin in chronic renal injury. Male Sprague-Dawley rats were used,
      and both nephropathy models were established at 1, 2, 4, and 8 weeks after
      surgery. There were no periglomerular calponin-positive cells in sham, PAN 1 and
      2 week, and SNx 1, 2, and 4 week groups. In SNx 8 week and PAN 4 and 8 week
      groups, only a few glomeruli with periglomerular calponin-reactivity, which
      covered half or a very small part of the periglomerular space, were observed. All
      glomeruli with periglomerular calponin-reactivity showed sclerotic changes,
      especially thickening of parietal epithelial cells (PECs). In conjunction with
      our previous report, this data represents the first documentation of the
      expression of calponin in renal myofibroblasts. We suggest that interactions
      between PECs and calponin-positive myofibroblasts may play a key role in the late
      stage of glomerulosclerosis.

PMID- 21189995
TI  - Systemic injection of recombinant human erythropoietin after focal cerebral
      ischemia enhances oligodendroglial and endothelial progenitor cells in rat brain.
AB  - Erythropoietin (EPO) has been demonstrated the ability of recombinant human
      erythropoietin (r-Hu-EPO), when administered intracerebro-ventricularly, to
      improve stroke outcome through the reduction of stroke damage. In a brain
      ischemic model, however, systemic administration of r-Hu-EPO has not been
      intensely investigated given that in general, large glycosylated molecules have
      been deemed incapable of crossing the blood-brain barrier. In this study,
      administration of r-Hu-EPO for 4 days, intraperitoneally after ischemia
      reperfusion (I-R) increased the number of bromodeoxyuridine (BrdU)-positive cells
      in the penumbra (10.1+/-1.4, n=5, P<0.05) and in the subventricular zone (SVZ) of
      the lateral ventricle (LV) (25+/-2.7, n=5, P<0.05) as compared with those of I-R
      (penumbra: 2.5+/-0.7; SVZ of LV: 3.8+/-1.5). A significant increase of BrdU
      positive cells in these areas was coincident with a strong immunoreactivity of
      oligodendrocyte progenitor cell marker (2', 3'-cyclic nucleotide 3'
      phosphodiesterase). Furthermore, r-Hu-EPO administration increased the number of
      BrdU-positive cells in the choroid plexus (7.8+/-2.3, n=5, P<0.05) and in
      cerebral blood vessels (3.5+/-1.3, n=5, P<0.05) when compared with those of I-R
      (choroid plexus: 1.2+/-0.5; cerebral blood vessels: 0.6+/-0.1). These results
      suggest that, even when systemically administered, r-Hu-EPO may have therapeutic
      potential for stroke via the proliferation of oligodendroglial and endothelial
      progenitor cells.

PMID- 21189996
TI  - Phosphorylation of 14-3-3zeta at serine 58 and neurodegeneration following kainic
      acid-induced excitotoxicity.
AB  - Oxidative stress-induced cell death leads to phosphorylation of 14-3-3zeta at
      serine 58. 14-3-3zeta is detected at significant levels in cerebrospinal fluid
      after kainic acid (KA)-induced seizures. Here we examined temporal changes in 14
      3-3zeta phosphorylation in the hippocampus and amygdala of mice after KA
      treatment. Mice were killed at 2, 6, 24, or 48 h after KA (30 mg/kg) injection.
      We observed an increase in TUNEL and Fluoro-Jade B (FJB)-stained neurons in the
      hippocampus and amygdala of KA-treated mice. Phospho (p)-14-3-3zeta and p-JNK
      expression was increased in the hippocampus 2 and 6 h after KA treatment,
      respectively. In immunohistochemical analysis, p-14-3-3zeta-positive cells were
      present in the CA3 region of the hippocampus and the central nucleus of amygdala
      (CeA) of KA-treated mice. Thus, phosphorylation of 14-3-3zeta at serine 58 may
      play an important role in KA-induced hippocampal and amygdaloid neuronal damage.

PMID- 21189997
TI  - Evaluation of recombinant adenovirus-mediated gene delivery for expression of
      tracer genes in catecholaminergic neurons.
AB  - Selective labeling of small populations of neurons of a given phenotype for
      conventional neuronal tracing is difficult because tracers can be taken up by all
      neurons at the injection site, resulting in nonspecific labeling of unrelated
      pathways. To overcome these problems, genetic approaches have been developed that
      introduce tracer proteins as transgenes under the control of cell-type-specific
      promoter elements for visualization of specific neuronal pathways. The aim of
      this study was to explore the use of tracer gene expression for neuroanatomical
      tracing to chart the complex interconnections of the central nervous system.
      Genetic tracing methods allow for expression of tracer molecules using cell-type
      specific promoters to facilitate neuronal tracing. In this study, the rat
      tyrosine hydroxylase (TH) promoter and an adenoviral delivery system were used to
      express tracers specifically in dopaminergic and noradrenergic neurons. Region
      specific expression of the transgenes was then analyzed. Initially, we
      characterized cell-type-specific expression of GFP or RFP in cultured cell lines.
      We then injected an adenovirus carrying the tracer transgene into several brain
      regions using a stereotaxic apparatus. Three days after injection, strong GFP
      expression was observed in the injected site of the brain. RFP and WGA were
      expressed in a cell-type-specific manner in the cerebellum, locus coeruleus, and
      ventral tegmental regions. Our results demonstrate that selective tracing of
      catecholaminergic neuronal circuits is possible in the rat brain using the TH
      promoter and adenoviral expression.

PMID- 21189998
TI  - Shape and innervation of popliteus muscle.
AB  - The aim of this study was to delineate the shape of the popliteus muscle and
      determine the correct motor point site for treating spasticity. A total of 22
      legs from 13 fresh Korean cadavers were evaluated. The x-axis was set as a
      transverse line across the lateral and medial epicondyle of the femur and the y
      axis as a vertical line at the midpoint of the medial malleolus of the tibia and
      lateral malleolus of the fibula. The popliteus muscle is an obtuse triangle in
      shape. Superior, medial, and inferior angles were 27.2+/-4.3 degrees , 114.8+/
      19.8 degrees , and 38.0+/-18.8 degrees  respectively. The lengths of the
      superior, medial, and lateral sides of the triangle were 7.6+/-1.0 cm, 6.2+/-1.0
      cm, and 11.9+/-1.5 cm respectively. Nerve branches ran superficially on the
      periosteum of the tibia and entered the popliteus on its superficial surface. The
      diverging point of the nerve branch entered the popliteus from the tibial nerve
      located at the midline of the popliteal fossa and 17% of the leg length above the
      intercondylar line. Most nerve entry points (83.3%) were within a 2.0*3.0 cm
      rectangle with the center located at -1.0 cm (-7%) on the x-axis and -3.3 cm (
      9%) on the y-axis.

PMID- 21189999
TI  - Improved analysis of palm creases.
AB  - Palm creases are helpful in revealing anthropologic characteristics and
      diagnosing chromosomal aberrations, and have been analyzed qualitatively and
      quantitatively. However, previous methods of analyzing palm creases were not
      objective so that reproducibility could not be guaranteed. In this study, a more
      objective morphologic analysis of palm creases was developed. The features of the
      improved methods include the strict definition of major and minor palm creases
      and the systematic classification of major palm creases based on their
      relationships, branches, and variants. Furthermore, based on the analysis of
      3,216 Koreans, palm creases were anthropologically interpreted. There was a
      tendency for palm creases to be evenly distributed on the palm, which was
      acknowledged by the relationship between major and minor creases as well as by
      the incidences of major creases types. This tendency was consistent with the role
      of palm creases to facilitate folding of palm skin. The union of major palm
      creases was frequent in males and right palms to have powerful hand grip. The new
      method of analyzing palm creases is expected to be widely used for anthropologic
      investigation and chromosomal diagnosis.

PMID- 21190001
TI  - Surgical anatomy of the lower eyelid relating to lower blepharoplasty.
AB  - The aim of this review is to familiarize the reader with the critical lower
      eyelid anatomy as is related to lower blepharoplasty or a midface lift. The
      contents include 1) the lacrimal canaliculus in the lower eyelid: the depth and
      width (diameter) of the vertical portion were 2.58+/-0.24 mm and 0.44+/-0.07 mm,
      respectively. A vertical portion of the canaliculus was about 1 mm (1.11+/-0.16
      mm) deep, and the horizontal portion was about 2~3 mm (2.08+/-2.74 mm) long 2 mm
      below the mucocutaneous junction, which is where an incision may be made when
      performing epicanthoplasty. 2) Motor innervation to the lower orbiculis oculi
      muscle: the pretarsal and preseptal OOMs were innervated by five to seven
      terminal twigs of the zygomatic branches of the facial nerve that approached the
      muscle at a right angle. The mean horizontal distance between the lateral canthus
      and the zygomatic branch was 2.31+/-0.29 cm (range: 1.7~2.7 cm) and the vertical
      distance was 1.20+/-0.20 cm (range: 0.8~1.5 cm). 3) Sensory innervation of the
      lower eyelid skin: the majority of the terminal branches (93.8%) of the ION were
      distributed to the medial to the lateral canthus. Most (99.4%) of the terminal
      branches of the ZFN were distributed to lateral to the lateral canthus. 4)
      Retractor of the lower eyelid; capsulopalpebral fascia (CPF): the orbital septum
      blended with the CPF most closely at 3.7~5.4 mm beneath the lower tarsal border
      and differently at 3.7+/-0.7 mm on the medial limbus line, 4.3+/-0.8 mm on the
      midpupillary line and 5.4+/-1.0 mm on the lateral limbus line. 5) Arcuate
      expansion (AE): The AE was a fibrous band expanding from the inferolateral
      orbital rim to the medial canthal ligament. A sector (fan-shaped) of the AE
      originated in the angle of 5 to 80 degrees at the circumference of the
      inferolateral orbital rim circle, falling within the range of 3 to 5.5 o'clock,
      and then it tapered and attached to the inferior border of the medial canthal
      ligament. 6) Suborbicularis oculi fat (SOOF) in the lower eyelid: the SOOF was
      located in the inferolateral side of the orbit within a range between medial +15
      and lateral -89 degrees to a vertical midpupillary line. Histologically, the SOOF
      was situated deep to the Orbicularis oculi muscle and superficial to the orbital
      septum and periosteum. The SOOF consisted more of fibrofatty tissue rather than
      being the pure fatty nature like orbital fat. I hope surgeons can achieve
      desirable outcomes with the knowledge reviewed in this article.

PMID- 21190002
TI  - Vitamin C acts indirectly to modulate isotype switching in mouse B cells.
AB  - Vitamin C, one of essential micronutrients, has been reported to modulate the
      humoral immune responses in some mammals. We investigated whether vitamin C might
      modulate this response in mice by directly affecting B cells. Splenic B cells
      were isolated and activated by CD40- and B cell receptor-ligation in vitro. The
      cells were cultured with a pretreatment of vitamin C from 0 to 1 mM of
      concentrations. Vitamin C slightly increased apoptosis of B cells dose
      dependently and behaved as an antioxidant. We found that in vivo administration
      of vitamin C by intraperitoneal injection affected isotype switching as
      previously reported: the titer of antigen-specific IgG1 antibody was decreased,
      while that of IgG2a was unaffected. Somewhat different from those observed in
      vivo, in vitro exposure to vitamin C slightly decreased isotype switching to IgG1
      and increased isotype switching to IgG2a. Pretreatment with vitamin C in the safe
      range did not affect either proliferation of cultured B cells or the expression
      of CD80 and CD86 in those cells. Taken together, in vivo results suggest that
      vitamin C acts to modulate isotype switching in the mouse. However, because of
      our in vitro results, we suggest that the modulation exerted by vitamin C in vivo
      is by indirectly affecting B cells, perhaps by directly influencing other immune
      cells such as dendritic cells.

PMID- 21190000
TI  - Genomics and proteomics in stem cell research: the road ahead.
AB  - Stem cell research has been widely studied over the last few years and has
      attracted increasing attention from researchers in all fields of medicine due to
      its potential to treat many previously incurable diseases by replacing damaged
      cells or tissues. As illustrated by hematopoietic stem research, understanding
      stem cell differentiation at molecular levels is essential for both basic
      research and for clinical applications of stem cells. Although multiple
      integrative analyses, such as genomics, epigenomics, transcriptomics and
      proteomics, are required to understand stem cell biology, proteomics has a unique
      position in stem cell research. For example, several major breakthroughs in HSC
      research were due to the identification of proteins such as colony-stimulating
      factors (CSFs) and cell-surface CD molecules. In 2007, the Human Proteome
      Organization (HUPO) and the International Society for Stem Cell Research (ISSCR)
      launched the joint Proteome Biology of Stem Cells Initiative. A systematic
      proteomics approach to understanding stem cell differentiation will shed new
      light on stem cell biology and accelerate clinical applications of stem cells.

PMID- 21190003
TI  - Inhibitory effects of curcumin on passive cutaneous anaphylactoid response and
      compound 48/80-induced mast cell activation.
AB  - Mast cells participate in allergies and inflammation by secreting a variety of
      pro-inflammatory mediators. Curcumin, the active component of turmeric, is a
      polyphenolic phytochemical with anti-tumor, anti-inflammatory, anti-oxidative,
      and anti-allergic properties. The effects of curcumin on compound 48/80-induced
      mast cell activation and passive cutaneous anaphylactoid reactions are unknown.
      In this report, we investigated the influences of curcumin on the passive
      cutaneous anaphylactoid response in vivo and compound 48/80-induced mast cell
      activation in vitro. The mechanism of action was examined by calcium uptake
      measurements and cAMP assays in mast cells. Curcumin significantly attenuated the
      mast cell-mediated passive cutaneous anaphylactoid reaction in an animal model.
      In agreement with this in vivo activity, curcumin suppressed compound 48/80
      induced rat peritoneal mast cell (RPMC) degranulation and histamine release from
      RPMCs. Moreover, compound 48/80-elicited calcium uptake into RPMCs was reduced in
      a dose-dependent manner by curcumin. Furthermore, curcumin increased the level of
      intracellular cAMP and significantly inhibited the compound 48/80-induced
      reduction of cAMP in RPMCs. These results corroborate the finding that curcumin
      may have anti-allergic activity.

PMID- 21190004
TI  - Recovered changes in the spleen by agmatine treatment after transient cerebral
      ischemia.
AB  - Stroke or cerebrovascular injury is the leading cause of disability and the third
      leading cause of deaths worldwide. After the initial ischemic injury, sympathetic
      signals are transmitted to the spleen and a compromised blood-brain barrier,
      coupled with expression of adhesion molecules by the vascular endothelial cells
      permits an influx of peripheral immune cells. This influx of peripheral immune
      cells into the brain exacerbates the local brain inflammatory response, leading
      to enhanced neurodegeneration. Agmatine is a primary amine formed by
      decarboxylation of L-arginine synthesized in the mammalian brain. In this study,
      we determined the effect of agmatine on the immune response in the spleen after
      transient cerebral ischemia. Twenty-three hours after transient cerebral
      ischemia, the white pulp area was reduced and the number of CD11b(+) macrophages
      and CD4(+)CD25(+) regulatory T cells (T reg cells) were increased in the spleens
      in the experimental group as a result of alteration of the immune response in the
      spleen, as regulated by inflammatory cytokines. In the agmatine treatment group
      (100 mg/kg IP), the contraction of white pulp was diminished and the number of
      CD11b(+) macrophages and CD4(+)CD25(+)T reg cells were decreased. Twenty-three
      hours after transient cerebral ischemia, the brain infarction area was
      significantly reduced (5.51+/-1.63% of the whole brain) in the agmatine treatment
      group compared to 15.02+/-4.28% of the whole brain in the experimental control
      group. These results suggest that agmatine treatment can reduce brain infarction
      through minimizing neuroinflammation and can lessen the danger of post-stroke
      infection from depression of the immune system after stroke.

PMID- 21190005
TI  - Effects of repeated restraint stress on platelet endothelial cell adhesion
      molecule-1 immunoreactivity and protein levels in the gerbil hippocampus after
      transient cerebral ischemia.
AB  - Stress has long been known to be a causative factor of various disease states. In
      this study, we investigated the effects of repeated restraint stress on platelet
      endothelial cell adhesion molecule-1 (PECAM-1), a very important mediator in
      inflammation, immunoreactivity and protein levels as well as neuronal damage, in
      the gerbil hippocampus after 5 minutes of transient cerebral ischemia. Transient
      ischemia-induced neuronal death was shown in CA1 pyramidal cells 4 days after
      ischemia/reperfusion. However, repeated restraint stress protected neuronal death
      induced by ischemic damage. In the ischemia-group, PECAM-1 immunoreactivity and
      its protein levels were significantly increased in all the hippocampal subregions
      4 days after ischemia/reperfusion. However, PECAM-1 immunoreactivity and its
      protein levels did not change significantly in the hippocampus of the stress
      ischemia-group compared to the sham-groups. These results indicate that repeated
      restraint stress protects neuronal damage induced by transient cerebral ischemia,
      and this may be associated with maintenance of PECAM-1levels.

PMID- 21190006
TI  - Immunohistochemical study on the expression of calcium binding proteins
      (calbindin-D28k, calretinin, and parvalbumin) in the cerebellum of the nNOS knock
      out(-/-) mice.
AB  - Nitric Oxide (NO) actively participates in the regulation of neuronal
      intracellular Ca(2+) levels by modulating the activity of various channels and
      receptors. To test the possibility that modulation of Ca(2+) buffer protein
      expression level by NO participates in this regulatory effect, we examined
      expression of calbindin-D28k, calretinin, and parvalbumin in the cerebellum of
      neuronal NO synthase knock-out (nNOS((-/-))) mice using immunohistochemistry. We
      observed that in the cerebellar cortex of the nNOS((-/-)) mice, expression of
      calbindin-D28k and parvalbumin were significantly increased while expression of
      calretinin was significantly decreased. These results suggest another mechanism
      by which NO can participate in the regulation of Ca(2+) homeostasis.

PMID- 21190007
TI  - TBR2-immunopsitive unipolar brush cells are associated with ectopic zebrin II
      immunoreactive Purkinje cell clusters in the cerebellum of scrambler mice.
AB  - Unipolar brush cells (UBCs) are excitatory interneurons with their somata located
      in the granular layer. Recently, T-brain factor 2 (Tbr2) was shown to be
      expressed in a subset of UBCs in mouse cerebellum. Scrambler mice exhibit severe
      cerebellum abnormalities, including the failure of embryonic Purkinje cell
      dispersal and a complete absence of foliation due to a mutation in the disabled-1
      adaptor protein. Since most UBC markers are expressed postnatally, it has proven
      difficult to identify the relationship between developing Purkinje cell clusters
      and migrating UBCs. Because scrambler mice closely mimic normal embryonic day 18
      cerebellum, we examined whether Tbr2-positive UBCs are associated with Purkinje
      cell cluster markers such as zebrin II, which is the most studied
      compartmentation marker in the cerebellum. We investigated the distribution of
      Tbr2-positive UBCs in this mutant by using anti-Tbr2 immunocytochemistry. The
      data revealed that Tbr2 immunoreactivity was exclusively present in the nucleus
      of UBCs in scrambler cerebellum. Based on expression data, a Tbr2-positive UBC
      map was constructed. In addition, Tbr2-positive UBCs are found associated with
      ectopic zebrin II-immunoreactive Purkinje cell clusters in scrambler cerebellum.
      These data suggest that UBCs use Purkinje cell compartmentation to migrate into
      their final position through interactions with the embryonic array of specific
      Purkinje cell subtypes.

PMID- 21190008
TI  - Chromatin organization and transcriptional activation of Hox genes.
AB  - Spatially and temporally programmed expression of the Hox genes along the antero
      posterior (A-P) axis is essential for correct pattern formation during embryonic
      development. An accumulating body of evidence indicates the pivotal role of
      spatial chromatin organization for the coordination of gene regulation. Recently,
      chromosome conformation capture (3C) technique has been developed and opened a
      new way to study chromosomal interactions in the nucleus. In this study, we
      describe 3C method we applied in F9 embryonic teratocarcinoma cells and
      demonstrate that the chromosomal interactions at Hox loci are successfully
      detected. Interestingly, at Hoxc loci, the abundance of intrachromosomal
      interactions with neighboring fragments was drastically decreased when the genes
      are expressed. These results indicate the possibility of the dynamic pattern of
      chromosomal interaction in association with the transcriptional regulation of Hox
      genes.

PMID- 21190009
TI  - Early cerebellar granule cell migration in the mouse embryonic development.
AB  - Pax6, a paired homeobox DNA binding protein, has been found to be expressed in
      the cerebellum in both granule cells and their precursors in the external
      granular layer (EGL). In this study we have traced Pax6 expression through
      embryonic development in mice by using a polyclonal antibody against Pax6 and
      used it to study the cellular dispersal pattern of the EGL. During dispersal the
      EGL was thicker and Pax6 expression was more intense on the rostral side of the
      lateral corners of the cerebellum. Pax6 immunoreactive cells were found to be
      migrating from the EGL during the early stage of EGL dispersal, which suggested
      the early inward migration of granule cells. Double staining with various markers
      confirmed that the early-migrating cells are not Purkinje cells, interneurons or
      glia. Although the Pax6 immunoreactive cells within the cerebellum were not
      apparently proliferating, NeuN, a marker for postmitotic granule cells, was not
      expressed in these cells until E16. Furthermore, granule cells were observed
      migrating inwards from the EGL both during and after EGL dispersal. These early
      migrating granule cells populated the whole cerebellum. These findings offer
      novel views on specific stages of granule cell dispersal and migration.

PMID- 21190010
TI  - Per capita sugar consumption is associated with severe childhood asthma: an
      ecological study of 53 countries.
AB  - AIMS: To examine the ecological association between population asthma symptom
      prevalence in six to seven year-old children and per capita sugar consumption
      seven years earlier (during the perinatal period). METHODS: The asthma data (from
      the International Study of Asthma and Allergies in Childhood [ISAAC] study) were
      collected between 1999 and 2004 from 53 countries, and per capita sugar
      consumption data (seven years before the asthma prevalence) were extracted from
      United Nations Food and Agriculture (UNFAO) food balance sheets. Linear
      regression and Spearman's rank coefficient were used to evaluate the relationship
      between exposure and disease outcome. RESULTS: Per capita sugar consumption
      varied more than six fold-between countries. A log-linear relationship was found
      between severe asthma symptoms (%) and per capita added sugar consumption in
      kg/capita/year (exponentiated beta coefficient 1.020; 95% CI 1.005 to 1.034; P =
      0.012). Spearman's rank correlation coefficient was 0.34 (P= 0.015), which
      indicates moderate correlation. CONCLUSIONS: We have demonstrated an ecological
      association between sugar consumption during the perinatal period and subsequent
      risk of severe asthma symptoms in six and seven year-olds.

PMID- 21190011
TI  - Developing and testing search strategies to identify patients with active
      seasonal allergic rhinitis in general practice.
AB  - AIM: We sought to assess the accuracy of different search terms to identify
      individuals with active seasonal allergic rhinitis (SAR) in general practice.
      METHODS: A reference search strategy was developed to identify patients with
      active SAR. This was applied through inspection of electronic health records of
      patients aged 15-45 years in a 10% random sample of a general practice database.
      Searches used Read codes and medication relating to SAR. Sensitivity,
      specificity, and positive and negative predictive values were calculated.
      RESULTS: Using the reference search strategy, 54/1092 (4.9%) of 15-45 year-old
      patients had current SAR. Searching for drugs used in nasal allergy had the
      highest sensitivity (85%) and good specificity (86%). Searching for a recorded
      history of SAR (H170) in the last two years was more specific (100%) but this
      approach only had limited sensitivity (17%). CONCLUSIONS: Electronic searches can
      be used to identify patients with current SAR, but the accuracy varies widely.
      Larger numbers of sufferers can be identified using broader search parameters,
      but with increasing numbers of false positives. In contrast, more focused search
      strategies give a smaller yield needing less cleaning of data to identify true
      positives, but there is an associated increase in the number of false negatives.

PMID- 21190013
TI  - Cumulative glycaemia as measured by lens fluorometry: association with
      retinopathy in type 2 diabetes.
AB  - AIMS/HYPOTHESIS: The aim of this study was to assess the association between
      lifelong cumulative glycaemia estimated by lens fluorometry and the presence of
      retinopathy in individuals with type 2 diabetes. METHODS: We carried out a cross
      sectional population-based study of 970 participants aged between 30 and 60
      years, of which 170 were diagnosed with diabetes on screening (WHO 1999 criteria)
      and 35 had known type 2 diabetes. Procedures included clinical and laboratory
      examinations, non-invasive assessment of the intrinsic fluorescence of the lens
      of the eye, and seven-field fundus photography. RESULTS: Retinopathy was found in
      46 (22%) of 205 participants with type 2 diabetes. In a logistic regression
      analysis controlling for age, sex and diabetes status (screen-detected or known),
      a two-fold increase in lens fluorescence increased the odds for retinopathy by
      3.46 (95% CI 1.25-9.55, p = 0.017). The association was marginally significant
      (OR 3.00 [95% CI 1.00-9.01], p = 0.050) when also adjusted for smoking, systolic
      blood pressure, body mass index and HbA(1c). CONCLUSIONS/INTERPRETATION: Diabetic
      retinopathy was related to cumulative lifelong glycaemia as estimated by lens
      fluorometry in participants with type 2 diabetes. This supports the hypothesis
      that retinopathy is a marker of lifelong elevated glycaemia as well as of the
      unknown, pre-diagnostic duration of type 2 diabetes. The powerful association
      between lens fluorescence and retinopathy underscores the importance of strict
      long-term glycaemic control in the prevention of retinopathy in people with
      diabetes.

PMID- 21190012
TI  - Mafa expression enhances glucose-responsive insulin secretion in neonatal rat
      beta cells.
AB  - AIM/HYPOTHESIS: Neonatal beta cells lack glucose-stimulated insulin secretion and
      are thus functionally immature. We hypothesised that this lack of glucose
      responsiveness results from a generalised low expression of genes characteristic
      of mature functional beta cells. Important glucose-responsive transcription
      factors, Mafa and Pdx1, regulate genes involved in insulin synthesis and
      secretion, and have been implicated in late beta cell development. The aim of
      this study was to assess whether Mafa and/or Pdx1 regulates the postnatal
      functional maturation of beta cells. METHODS: By quantitative PCR we evaluated
      expression of these and other beta cell genes over the first month compared with
      adult. After infection with adenovirus expressing MAFA, Pdx1 or green fluorescent
      protein (Gfp), P2 rat islets were evaluated by RT-PCR and insulin secretion with
      static incubation and reverse haemolytic plaque assay (RHPA). RESULTS: At P2 most
      beta cell genes were expressed at about 10% of adult, but by P7 Pdx1 and Neurod1
      no longer differ from adult; by contrast, Mafa expression remained significantly
      lower than adult through P21. Overexpression of Pdx1 increased Mafa, Neurod1,
      glucokinase (Gck) mRNA and insulin content but failed to enhance glucose
      responsiveness. Similar overexpression of MAFA resulted in increased Neurod1,
      Nkx6-1, Gck and Glp1r mRNAs and no change in insulin content but, importantly,
      acquisition of glucose-responsive insulin secretion. Both the percentage of
      secreting beta cells and the amount of insulin secreted per beta cell increased,
      approaching that of adult beta cells. CONCLUSIONS/INTERPRETATION: In the process
      of functional maturation acquiring glucose-responsive insulin secretion, neonatal
      beta cells undergo a coordinated gene expression programme in which Mafa plays a
      crucial role.

PMID- 21190015
TI  - Greenhouse study on the phytoremediation potential of vetiver grass, Chrysopogon
      zizanioides L., in arsenic-contaminated soils.
AB  - The purpose of this greenhouse study was to assess the capacity of vetiver grass
      to accumulate arsenic from pesticide-contaminated soils of varying physico
      chemical properties. Results indicate that vetiver is capable of tolerating
      moderate levels of arsenic up to 225 mg/kg. Plant growth and arsenic removal
      efficiency was strongly influenced by soil properties. Arsenic removal was
      highest (10.6%) in Millhopper soil contaminated with 45 mg/kg arsenic, which
      decreased to 4.5 and 0.6% at 225 and 450 mg/kg, respectively. High biomass,
      widespread root system and environmental tolerance make this plant an attractive
      choice for the remediation of soils contaminated with moderate levels of arsenic.

PMID- 21190014
TI  - Knockdown of the gene encoding Drosophila tribbles homologue 3 (Trib3) improves
      insulin sensitivity through peroxisome proliferator-activated receptor-gamma
      (PPAR-gamma) activation in a rat model of insulin resistance.
AB  - AIMS/HYPOTHESIS: Insulin action is purportedly modulated by Drosophila tribbles
      homologue 3 (TRIB3), which in vitro prevents thymoma viral proto-oncogene (AKT)
      and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation.
      However, the physiological impact of TRIB3 action in vivo remains controversial.
      METHODS: We investigated the role of TRIB3 in rats treated with either a control
      or Trib3 antisense oligonucleotide (ASO). Tissue-specific insulin sensitivity was
      assessed in vivo using a euglycaemic-hyperinsulinaemic clamp. A separate group
      was treated with the PPAR-gamma antagonist bisphenol-A-diglycidyl ether (BADGE)
      to assess the role of PPAR-gamma in mediating the response to Trib3 ASO. RESULTS:
      Trib3 ASO treatment specifically reduced Trib3 expression by 70% to 80% in liver
      and white adipose tissue. Fasting plasma glucose, insulin concentrations and
      basal rate of endogenous glucose production were unchanged. However, Trib3 ASO
      increased insulin-stimulated whole-body glucose uptake by ~50% during the
      euglycaemic-hyperinsulinaemic clamp. This was attributable to improved skeletal
      muscle glucose uptake. Despite the reduction of Trib3 expression, AKT2 activity
      was not increased. Trib3 ASO increased white adipose tissue mass by 70% and
      expression of Ppar-gamma and its key target genes, raising the possibility that
      Trib3 ASO improves insulin sensitivity primarily in a PPAR-gamma-dependent
      manner. Co-treatment with BADGE blunted the expansion of white adipose tissue and
      abrogated the insulin-sensitising effects of Trib3 ASO. Finally, Trib3 ASO also
      increased plasma HDL-cholesterol, a change that persisted with BADGE co
      treatment. CONCLUSIONS/INTERPRETATION: These data suggest that TRIB3 inhibition
      improves insulin sensitivity in vivo primarily in a PPAR-gamma-dependent manner
      and without any change in AKT2 activity.

PMID- 21190016
TI  - Contribution of GABA(A) receptors containing alpha3 subunits to the therapeutic
      related and side effects of benzodiazepine-type drugs in monkeys.
AB  - RATIONALE: Experimental evidence suggests that the differential behavioral
      effects of benzodiazepines depend on their relative actions at gamma-aminobutyric
      acid type A (GABA(A)) receptors that contain either an alpha1, alpha2, alpha3, or
      alpha5 subunit. OBJECTIVES: The present study was aimed at understanding the role
      of alpha3 subunit-containing GABA(A) (alpha3GABA(A)) receptors by examining the
      behavioral pharmacology of TP003 (4,2'-difluoro-5'-[8-fluoro-7-(1-hydroxy-1
      methylethyl)imidazo[1,2-a]pyridine-3-yl]biphenyl-2-carbonitrile), which shows
      functional selectivity for alpha3GABA(A) receptors. METHODS: First, a conflict
      procedure was used to assess the anxiolytic-like effects of TP003 and a
      representative clinically available benzodiazepine. TP003 was also administered
      before daily periods of sucrose pellet availability to evaluate potential
      hyperphagic effects. In separate experiments, observable behavioral effects were
      used to assess the motor and sedative effects of TP003. RESULTS: Administration
      of TP003 produced robust anti-conflict effects without the rate-decreasing
      effects that were observed with the representative benzodiazepine. Unlike the
      reported effects of benzodiazepines, TP003 did not enhance palatable food
      consumption. However, increases in observable sleep-associated posture were
      induced by TP003, as were decreases in some species-typical behaviors
      (vocalization, locomotion, and environment-directed behaviors). When evaluated
      for its ability to induce a procumbent posture, TP003 failed to produce an
      effect. CONCLUSIONS: Based on conflict and observation tests in monkeys, our
      results suggest that TP003 may have anxiolytic properties but lack ataxic,
      hyperphagic, and pronounced sedative effects characteristic of classical
      benzodiazepines. TP003 did induce myorelaxant-like effects and had relatively
      mild sedative effects. Collectively, these results suggest that alpha3GABA(A)
      receptors play an important role in the anxiolytic-like and motor effects of
      benzodiazepine-type drugs.

PMID- 21190017
TI  - Characterization of the 3D angular vestibulo-ocular reflex in C57BL6 mice.
AB  - We characterized the three-dimensional angular vestibulo-ocular reflex (3D aVOR)
      of adult C57BL6 mice during static tilt testing, sinusoidal, and high
      acceleration rotations and compared it with that of another lateral-eyed mammal
      with afoveate retinae (chinchilla) and two primate species with forward eye
      orientation and retinal foveae (human and squirrel monkey). Noting that visual
      acuity in mice is poor compared to chinchillas and even worse compared to
      primates, we hypothesized that the mouse 3D aVOR would be relatively low in gain
      (eye-velocity/head-velocity) compared to other species and would fall off for
      combinations of head rotation velocity and frequency for which peak-to-peak
      position changes fall below the minimum visual angle resolvable by mice. We also
      predicted that as in chinchilla, the mouse 3D aVOR would be more isotropic
      (eye/head velocity gain independent of head rotation axis) and better aligned
      with the axis of head rotation than the 3D aVOR of primates. In 12 adult C57BL6
      mice, binocular 3D eye movements were measured in darkness during whole-body
      static tilts, 20-100 degrees /s whole-body sinusoidal rotations (0.02-10 Hz) and
      acceleration steps of 3,000 degrees /s2 to a 150 degrees /s plateau (dominant
      spectral content 8-12 Hz). Our results show that the mouse has a robust static
      tilt counter-roll response gain of ~0.35 (eye-position Delta/head-position Delta)
      and mid-frequency aVOR gain (~0.6-0.8), but relatively low aVOR gain for high
      frequency sinusoidal head rotations and for steps of head rotation acceleration
      (~0.5). Due to comparatively poor static visual acuity in the mouse, a perfectly
      compensatory 3D aVOR would confer relatively little benefit during high
      frequency, low-amplitude movements. Therefore, our data suggest that the adaptive
      drive for maintaining a compensatory 3D aVOR depends on the static visual acuity
      in different species. Like chinchillas, mice have a much more nearly isotropic 3D
      aVOR than do the primates for which comparable data are available. Relatively
      greater isotropy in lateral-eyed species without retinal foveae (e.g., mice and
      chinchillas in the present study) compared to forward-eyed species with retinal
      foveae (e.g., squirrel monkeys and humans) suggests that the parallel resting
      optic axes and/or radially symmetric retinal foveae of primates underlie their
      characteristically low 3D aVOR gain for roll head rotations.

PMID- 21190018
TI  - Understanding adherence to therapeutic guidelines: a multilevel analysis of
      statin prescription in the Skaraborg Primary Care Database.
AB  - PURPOSE: In Skaraborg, Sweden, the economic responsibility for tax-financed
      prescription drug costs was transferred from the regional administrative level to
      the local level (health care centre; HCC) in 2003. The aim of this study was to
      investigate the impact of this decentralization of economic responsibility on
      adherence to guidelines for prescribing lipid-lowering drugs. METHODS: Data from
      all 24 public HCCs in Skaraborg on prescriptions for lipid-lowering drugs during
      2003 and 2005 were extracted from the Skaraborg Primary Care Database (SPCD).
      Multilevel regression analysis (MLRA) was used to disentangle the variances at
      different levels of data (patient, physician, HCC). The outcome variable on the
      patient level was the prescription of the recommended statin (yes/no). Sex and
      age of the patients and sex, age and occupational status of the physician were
      included as fixed effects. The variance was expressed as the median odds ratio
      (MOR). RESULTS: The prevalence of adherence to guidelines for the prescription of
      statins increased from 77% in 2003 to 84% in 2005. The MLRA showed that in 2003
      the variance was equally distributed between the HCC and physician levels
      (MOR(HCC2003)=1.89 vs. MOR(PHYSICIAN2003)=1.88). The variance between physicians
      and between HCCs decreased considerably between 2003 and 2005. The inclusion of
      individual and physician characteristics did not explain any of the remaining
      variance. CONCLUSION: The decentralized budget appears to have increased
      adherence to guidelines and reduced inefficient variation in prescribing.

PMID- 21190019
TI  - The effect of diclofenac sodium on renal function in reversible unilateral
      ureteric obstruction.
AB  - The objective of the study was to investigate the effect of diclofenac sodium,
      when administered similar to its use in clinical practice, 2 weeks following
      different periods of complete reversible unilateral ureteric obstruction in the
      rat using accurate indicators of renal function. Male Wistar rats underwent
      reversible left ureteric obstruction for 2 days [D2-untreated (n = 8) and D2-DS
      (n = 8) groups] and 5 days [D5-untreated (n = 7) and D5-DS (n = 7) groups]. D2-DS
      and D5-DS received intramuscular diclofenac sodium (3 mg/kg per day) during the
      time of obstruction, whereas D2-untreated and D5-untreated groups did not receive
      any treatment. The renal functions of both kidneys were studied 2 weeks following
      the reversal. The basal heart rate and mean arterial blood pressure were similar
      in D2-untreated and D2-DS and in D5-untreated and D5-DS groups. In the D2
      untreated group, the GFR and RBF of the left obstructed kidney were 76 and 72%
      that of the right non-obstructed kidney [0.99 +/- 0.06 vs. 1.30 +/- 0.08 (P <
      0.05) and 4.25 +/- 0.33 vs. 5.92 +/- 0.61 (P < 0.05), respectively]. The urine
      volume and urinary and fractional sodium excretion were not significantly
      different from the right kidney. Similar response was obtained in the D2-DS
      group. In the D5-untreated group, the GFR and RBF of the left kidney was 66 and
      62% that of the right kidney (0.80 +/- 0.12 vs. 1.21 +/- 0.6, P < 0.05 and 3.79
      +/- 0.32 vs. 6.16 +/- 0.59, P < 0.05; respectively). The tubular functions of
      both kidneys were similar. In the D5-DS group, there was no difference in GFR or
      RBF between both kidneys (1.02 +/- 0.08 vs. 1.12 +/- 0.3, P = 0.24 and 5.10 +/-
      1.25 vs. 6.46 +/- 1.11, P = 0.44, respectively). Similarly, there was no
      difference in the tubular functions. Treatment with diclofenac sodium during a
      relatively long period of reversible unilateral ureteric obstruction, similar to
      its use in the management of ureteric colic, appears to ameliorate the
      alterations in the hemodynamic glomerular functions at least 2 weeks following
      the reversal of obstruction.

PMID- 21190020
TI  - Radiologic findings of adult pelvis and appendicular skeletal Langerhans cell
      histiocytosis in nine patients.
AB  - OBJECTIVE: The purpose of this article was to evaluate the radiologic findings of
      adult pelvis and appendicular skeletal Langerhans cell histiocytosis (LCH),
      emphasizing the CT and MR findings. MATERIALS AND METHODS: The images of nine
      patients with pathologically proven LCH (five men and four women; mean age, 37.11
      years) were retrospectively reviewed. Imaging analysis was confined to the long
      and flat bones. CT scans were performed in five patients and MR imaging was
      performed in eight. Images were assessed for the following features on CT and
      MRI: the location and number of lesions; the presence of cortical destruction,
      endosteal scalloping, and a periosteal reaction on CT or MRI; the margin of soft
      tissue masses, the presence of bone marrow edema, and a "budding" appearance on
      MRI; and the presence of sclerotic margins or septations on CT. RESULTS: The
      involved skeletal sites were the pelvis (seven), femurs (five), humeri (two),
      tibias (two), fibula (one), clavicle (one), scapula (one), and sternum (one).
      Endosteal scalloping, a periosteal reaction, and a budding appearance were common
      on MRI or CT images. Although cortical destruction and the soft tissue lesion
      formation were rare, soft tissue masses had well-defined margins. CONCLUSIONS:
      Endosteal scalloping and a budding appearance with a periosteal reaction on CT
      and MRI may be helpful signs for differentiation of LCH from malignant tumors in
      adults.

PMID- 21190021
TI  - The fate of priority areas for conservation in protected areas: a fine-scale
      Markov chain approach.
AB  - Park managers in alpine areas must deal with the increase in forest coverage that
      has been observed in most European mountain areas, where traditional farming and
      agricultural practices have been abandoned. The aim of this study is to develop a
      fine-scale model of a broad area to support the managers of Paneveggio Nature
      Park (Italy) in conservation planning by focusing on the fate of priority areas
      for conservation in the next 50-100 years. GIS analyses were performed to assess
      the afforestation dynamic over time using two historical maps (from 1859 and
      1936) and a series of aerial photographs and ortho-photos (taken from 1954 to
      2006) covering a time span of 150 years. The results show an increase in the
      forest surface area of about 35%. Additionally, the forest became progressively
      more compact and less fragmented, with a consequent loss of ecotones and open
      habitats that are important for biodiversity. Markov chain-cellular automata
      models were used to project future changes, evaluating the effects on a habitat
      scale. Simulations show that some habitats defined as priority by the EU Habitat
      Directive will be compromised by the forest expansion by 2050 and suffer a
      consistent loss by 2100. This protocol, applied to other areas, can be used for
      designing long-term management measures with a focus on habitats where
      conservation status is at risk.

PMID- 21190022
TI  - Imaging of the Achilles tendon in spondyloarthritis: a comparison of ultrasound
      and conventional, short and ultrashort echo time MRI with and without intravenous
      contrast.
AB  - OBJECTIVES: To compare conventional MRI, ultrashort echo time MRI and ultrasound
      for assessing the extent of tendon abnormalities in spondyloarthritis. METHODS:
      25 patients with spondyloarthritis and Achilles symptoms were studied with MRI
      and ultrasound. MR images of the Achilles tendon were acquired using T1-weighted
      spin echo, gradient echo and ultrashort echo time (UTE) sequences with echo times
      (TE) between 0.07 and 16 ms, before and after intravenous contrast medium.
      Greyscale and power Doppler ultrasound were also performed. The craniocaudal
      extent of imaging abnormalities measured by a consultant musculoskeletal
      radiologist was compared between the different techniques. RESULTS: Abnormalities
      were most extensive on spoiled gradient echo images with TE = 2 ms. Contrast
      enhancement after intravenous gadolinium was greatest on the UTE images (TE =
      0.07 ms). Fewer abnormalities were demonstrated using unenhanced UTE.
      Abnormalities were more extensive on MRI than ultrasound. Contrast enhancement
      was more extensive than power Doppler signal. CONCLUSIONS: 3D spoiled gradient
      echo images with an echo time of 2 ms demonstrate more extensive tendon
      abnormalities than the other techniques in spondyloarthritis. Abnormalities of
      vascularity are best demonstrated on enhanced ultrashort echo time images.

PMID- 21190023
TI  - External validation and applicability of the EORTC risk tables for non-muscle
      invasive bladder cancer.
AB  - PURPOSE: To perform an external validation of the EORTC risk tables and to
      evaluate their applicability in the patients of our institution by comparing the
      actual risk of recurrence and progression in our series to those obtained through
      the application of the EORTC tables. METHODS: Retrospective study, based on a
      prospective cohort of 417 patients in follow-up with primary TaT1 bladder tumors,
      operated on in our center between 1998 and 2008 and collected in our database.
      Risk scores were assigned depending on the tumor characteristics to divide our
      series into four risk groups according to these ratings. An analysis of survival
      was carried out to calculate the probability of recurrence by the method of
      Kaplan-Meier. RESULTS: A total of 417 patients with a median follow-up of 59
      months were studied. The overall recurrence and progression rates of our series
      were 25.95% (21.97-30.49) and 4.86% (3.16-7.43) at 1 year and 53.46% (48.06
      59.05) and 8.43% (5.95-11.86) at 5 years, respectively. When we compare our rates
      of recurrence and progression by groups with the corresponding values from
      Sylvester's publication, an overlapping of the confidence intervals between both
      populations is detected. CONCLUSIONS: In terms of the applicability of the EORTC
      risk tables in our patients' population, we conclude that these tables predict
      accurately the clinical course of patients with NMIBC. Due to the sample size of
      our study, we can only validate the recurrence model of the EORTC tables.

PMID- 21190024
TI  - Long-term sequelae after acquired pediatric hemorrhagic cerebellar lesions.
AB  - PURPOSE: The aim of the present study was to assess cognitive, affective, and
      motor long-term sequelae after acquired focal pediatric cerebellar lesions.
      METHODS: Eight patients with a history of isolated acquired hemorrhagic
      cerebellar lesions before the age of 13 participated in this study. All
      participants underwent a neurologic examination, including the Zurich Neuromotor
      Assessment (ZNA) and the International Cooperative Ataxia Rating Scale (ICARS).
      Cognitive functions have been evaluated with a general cognitive assessment and
      an extensive neuropsychological battery. Furthermore, patients and parents filled
      in questionnaires about quality of life and possible behavioral or emotional
      problems. RESULTS: The results revealed that all patients exhibited motor
      problems (ZNA). Most participants had further restricted oculomotor movements
      (ICARS). Age at injury and the full scale IQ were significantly positively
      correlated (Pearson correlation 0.779; p = 0.023). Conversely, no overall
      neuropsychological profile could be identified except for marginally reduced
      reaction times and susceptibility to interference. In addition, borderline
      results in semantic and phonemic word fluency tasks were apparent. A dysexecutive
      syndrome was diagnosed in one patient. However, verbal performance and reading
      abilities were non-pathologic in all participants. The patients reported having a
      good quality of life without major physical restrictions. CONCLUSIONS: Emotional
      disturbances and the presence of a mild cerebellar cognitive affective syndrome
      (as frequently described in adult patients) could only be confirmed in
      adolescents with vermis lesions. Nevertheless, in laboratory conditions,
      neuropsychological impairments were present in all patients. Heterogeneity of age
      at injury and exact lesion site may have led to interpersonal differences in
      neuropsychological outcome.

PMID- 21190025
TI  - Low preoperative serum albumin in colon cancer: a risk factor for poor outcome.
AB  - OBJECTIVE: The number of colon cancer patients is increasing worldwide.
      Malnutrition and comorbidities are frequently associated with these patients. The
      relationships between the preoperative malnutrition and the outcomes of colon
      cancer patients are unclear; this study aimed to clarify these issues. METHODS: A
      total of 3,849 consecutive colon cancer patients were enrolled in an analysis of
      short-term outcomes and 2,529 patients were included in an analysis of the long
      term outcomes. These patients were divided into the hypoalbuminemic and normal
      groups according to the definition of hypoalbuminemia (serum albumin < 35 g/L).
      RESULTS: Advanced age, female gender, abnormal CEA levels, right colon or large
      tumors, mucinous adenocarcinoma, poor differentiation, stage II cancer, TNM
      advancing T stage, old cardiovascular accident, diabetes, and liver cirrhosis
      were more likely to be associated with hypoalbuminemia. Hypoalbuminemic patients
      had a higher rate of postoperative mortality and morbidity, including
      complications related to wounds, lungs, the urinary system, and anastomosis. The
      5-year overall survival rates of patients with normal albumin and hypoalbuminemia
      were 78.0% and 60.0%, respectively (P < 0.0001), and the 5-year relapse-free
      survival rates were 78.9% and 73.5%, respectively (P = 0.0042). In a multivariate
      analysis, the albumin level was also significantly correlated with 5-year overall
      survival (<35 vs. >= 35, HR 1.75; 95% CI 1.49-2.08) and 5-year relapse-free
      survival (<35 vs. >= 35, HR 1.28; 95% CI 1.04-1.56). CONCLUSIONS: Hypoalbuminemia
      is a predictor of poor surgical outcomes of colon cancer and is a poor prognosis
      factor for long-term survival of colon cancer after curative operation.

PMID- 21190026
TI  - Health-related quality of life and colorectal cancer-specific symptoms in
      patients with chemotherapy-refractory metastatic disease treated with
      panitumumab.
AB  - PURPOSE: Panitumumab monotherapy is approved for chemotherapy-refractory wild
      type KRAS metastatic colorectal cancer (mCRC). Patient-reported outcomes-although
      important in the palliative setting-have not been reported in this patient
      population. METHODS: In a phase 3 trial (n = 463), patients with chemotherapy
      refractory mCRC were randomized 1:1 to panitumumab plus best supportive care
      (BSC) or BSC alone. Patient-reported outcomes were assessed using the NCCN/FACT
      CRC Symptom Index (FCSI) and EQ-5D Index. KRAS tumor status was analyzed in a
      prospectively defined, retrospective analysis. Average difference in change from
      baseline between treatment groups was evaluated using linear mixed and pattern
      mixture models. RESULTS: KRAS tumor status and post-baseline patient-reported
      outcomes were available for 363 patients. Linear mixed models indicated
      significant differences in the FCSI score (difference in least-squares [LS]
      adjusted means [95% CI]; 5.62 [2.38, 8.86]) and the EQ-5D Index (difference in LS
      adjusted means [95% CI]; 0.22 [0.12, 0.32]) favoring panitumumab over BSC in
      patients with wild-type KRAS mCRC. By pattern-mixture analysis, the advantage of
      panitumumab over BSC was more pronounced in those patients with wild-type KRAS
      mCRC who did not drop out of the study early. In patients with mutant KRAS mCRC,
      no differences were observed between groups. CONCLUSIONS: Panitumumab-treated
      patients with wild-type KRAS mCRC maintained better control of CRC symptoms and
      quality of life compared with BSC alone, extending our understanding of the
      benefits of panitumumab treatment beyond improvements in progression-free
      survival.

PMID- 21190027
TI  - Laparoscopic-assisted low anterior resection of the rectum--a review of the
      fascial composition in the pelvic space.
AB  - INTRODUCTION: Outcomes of rectal cancer treatment depend on the operative
      technique, and complication rates vary. Complications can occur during
      mobilization of the rectum, with damage to the ureter, autonomic nerves, and the
      rectum itself. Frequencies of these complications can be reduced by careful
      dissection of the correct tissue plane in the pelvic space. METHODOLOGY: This
      paper reviews the fascial composition of the rectum for low anterior resection of
      the rectum. To date, fascial composition of the pelvic space has been considered
      based on clinical anatomy and histological examination of cadaveric specimens.
      However, clarification of fascial composition is clearly limited, to a certain
      extent, in histological examinations compared with clinical anatomy. CONCLUSIONS:
      First, some degree of dissociation must exist between the histological
      examination and clinical anatomy. Second, surgeons should not consider fascia
      encountered intraoperatively as an artifact. To address these difficult issues,
      consideration should be made purely from the perspective of clinical anatomy.
      Originally, the trunk was embryologically regarded as a multi-layered structure
      (like an onion). Understanding the fascial composition of the abdomen is
      comparatively easy when approached from this perspective. If this theory is
      adapted to the pelvic space in order to avoid antilogy, an understanding of the
      fascial composition of the pelvic space should also be possible. We review
      previous papers based on this theory.

PMID- 21190028
TI  - Fibrin glue in the endoscopic treatment of fistulae and anastomotic leakages of
      the gastrointestinal tract.
AB  - BACKGROUND: Fistulae or leakages of anastomotic junctions of the gastrointestinal
      tract used to be an indication for surgery. However, patients often are severely
      ill and endoscopic therapeutic options have been suggested to avoid surgical
      intervention. PURPOSE: This is a retrospective analysis of fibrin glue
      application in the treatment of gastrointestinal fistulae or anastomotic
      leakages. AIM: The aim of this study was to investigate the value of fibrin glue
      in the treatment of gastrointestinal fistulae and leakages. METHODS: From
      September 1996 to November 2002, 52 patients with gastrointestinal fistulae or
      insufficiencies have been treated endoscopically including the use of fibrin glue
      (Tissucol Duo S(r), Baxter, Unterschleissheim, Germany). Clinical data comprising
      concomitant therapies and results were analysed by chart review. RESULTS: Twenty
      six lesions were located in the oesophagus or gastroesophageal junction, 4 in the
      stomach, 7 in the small intestine, 13 colorectal and 2 in the pancreas. The
      duration of treatment ranged from 12 to 1,765 days. Two to 81 ml fibrin glue
      (median 8.5) was used in 1-40 sessions (median 4). All patients received
      antibiotics; additional endoscopic options were frequently applied. Endoscopic
      therapy cured 55.7% patients (n = 29); 36.5% (n = 19) were cured with fibrin glue
      as sole endoscopic option. In 23.1% (n = 12), surgical intervention became
      necessary. Patients without major infectious complications tended to have a
      higher cure rate without surgery (87.5% vs. 50%). Eleven patients died (21.1%).
      CONCLUSION: Endoscopic therapy is a valuable option in the treatment of fistulae
      and anastomotic insufficiencies of the gastrointestinal tract. It usually is
      applied repeatedly. Fibrin glue is a mainstay of this procedure. Major infectious
      complications seem to define a subgroup of patients with poorer outcome.

PMID- 21190029
TI  - Rotator cuff changes in a full thickness tear rat model: verification of the
      optimal time interval until reconstruction for comparison to the healing process
      of chronic lesions in humans.
AB  - BACKGROUND: The aim of the study was to develop a standardized rat model for
      chronic rotator cuff tears. Therefore, a time point of degenerative changes that
      shows comparable histological changes to the chronic tendon tears in humans had
      to be determined. The rat shoulder has already been described as a standardized
      model for investigation of the healing behavior in acute supraspinatus lesions.
      Little data exist about the possibility of generating a chronic rotator cuff
      lesion. METHODS: We performed a complete detachment of the supraspinatus tendon
      in 45 Sprague-Dawley rats. After an interval of 3, 6 and 9 weeks (15 rats in each
      group), the macroscopic and histological changes were analyzed. The histological
      investigation included atrophy and fatty muscle degeneration, tendon degeneration
      and the grade of inflammatory changes. For evaluation of tendon degeneration, a
      modified MOVIN-Score was used. The contralateral shoulder provided as control
      group. RESULTS: Macroscopically the defect showed an increasing coverage with
      scar tissue over time with a complete closure in 73% after 9 weeks. The 3 week
      group showed the highest rate of persisting defects (80%). The atrophy of the
      supraspinatus muscle decreased from initial slight atrophy to a nearly normal
      muscle status in the 9 week group. Fatty infiltration was found in three animals
      per group regardless of the time interval after detachment. Tendon degeneration
      (modified MOVIN-Score) showed no significant difference between 3 and 6 weeks (p
      = 0.93) whereas after 9 weeks a significant increased degeneration was found (p <
      0.01). In the early phase (3 and 6 weeks), inflammatory cells could be detected
      more frequently. CONCLUSIONS: The results show that a chronic tear of the human
      rotator cuff can be imitated in the rat model with some exclusion. The rapid self
      healing response in the rat and the fatty infiltration of the human muscle are
      the main differences. However, tendon degeneration, inflammation and muscle
      atrophy combined with a persisting defect at 3 weeks after detachment are
      comparable to the chronic tendon tears in humans. This model can serve as a basis
      for further research in the field of rotator cuff repair for chronic lesions.

PMID- 21190030
TI  - The longer pull-out suture as a transmission suture for early active motion of
      repaired flexor tendon at the proximal zone-2.
AB  - OBJECTIVES: The purpose of the current study was to clinically evaluate the
      technique of longer pull-out suture as a transmission suture for early active
      motion after flexor tendon repair in the proximal zone-2. METHOD: Eleven patients
      (eight adult male, two adult female and one child) with 19 proximal zone II
      flexor tendon lacerations were included. Mean age was 35 years. The patients were
      encouraged to perform active mobilization of the injured digits by themselves
      with full range of flexion from the first postoperative day. The pull-out suture
      was removed at the 8-10 weeks after the operation. RESULTS: The mean follow-up
      was 39 months. The procedure was well tolerated by all of the patients. A patient
      of whom pull-out suture was traumatized and loosened at 6th week showed fair
      result. Two other patients with a history of blunt trauma were also found to have
      fair results. Overall 16 of the 19 digits were evaluated as excellent or good by
      the Strickland criteria. CONCLUSION: The results of this method show that the
      longer pull-out suture technique as a transmission suture followed by early
      active mobilization is safe, has a low re-rupture rate and is easy to perform for
      proximal zone-2 flexor tendon injuries.

PMID- 21190031
TI  - Biomechanical effect of different interspinous devices on lumbar spinal range of
      motion under preload conditions.
AB  - INTRODUCTION: Interspinous devices are used as an alternative to the current gold
      standard treatment, decompressive surgery with or without fusion, for lumbar
      spinal stenosis. They are supposed to limit extension and expand the spinal canal
      and foramen at the symptomatic level, but still allow lateral bending and axial
      rotation in the motion segment. The aim of the present study is the biomechanical
      evaluation of the change in the range of motion of the affected and adjacent
      segments following implantation of different interspinous devices under load in
      all directions of motion. METHOD: Eight fresh frozen human cadaver lumbar spines
      (L2-L5) were tested in a spinal testing device with a moment of 7.5 nm in
      flexion/extension, lateral bending and rotation with and without a preload
      (follower load of 400 N). The ROM was measured after implantation of Aperius
      (Kyphon, Mannheim), In-Space (Synthes, Umkirch), X-Stop (Tikom, Furth) and Coflex
      (Paradigm Spine, Wurmlingen) into the segment L3/L4. RESULTS: All interspinous
      devices caused a significant reduction in extension of the instrumented segment
      without significantly affecting the other directions of motion. The flexion was
      reduced by all implants only when the follower load was applied. All devices
      caused a higher ROM of the whole spine during lateral bending and rotation.
      CONCLUSION: The actual evaluated interspinous devices led to a significant
      reduction in ROM during flexion-extension, but to a significant increase in ROM
      for the whole specimen (L2-L5) during lateral bending and rotation, which could
      increase the risk of adjacent segment degeneration.

PMID- 21190032
TI  - The impact of the 2008 financial crisis on psychological work stress among
      financial workers and lawyers.
AB  - PURPOSE: The aim of this study was to investigate the impact of the financial
      crisis on psychological work stress among financial workers and lawyers. METHODS:
      The Chinese versions of Karasek's job content questionnaire (C-JCQ) and
      Siegrist's ERI questionnaire (C-ERI) were used to measure work stress, and the
      Copenhagen Burnout Inventory (C-CBI) questionnaire was used to measure personal
      and work-related burnout for 38 financial workers and 97 lawyers before and after
      the financial crisis in 2008. A paired t test was used to compare changes in work
      stress and burnout. A logistic regression was performed to determine the
      association between psychosocial work stress and burnout. RESULTS: After the
      financial crisis, financial workers reported significantly higher stress from
      fear of layoffs, increased experiences of undesirable changes and more fear of
      making mistakes during work. On the contrary, lawyers reported significantly
      higher scores of reward, fewer psychological demands and less exhaustion. In
      addition to high psychological demand and a high effort-reward ratio, high
      effort, over-commitment and stress of layoffs also contributed to personal and
      work-related burnout after the financial crisis. After the financial crisis,
      lawyers' personal burnout decreased with the increase of reward, and their work
      related burnout decreased with the decrease in psychological demand. CONCLUSIONS:
      The financial crisis has an unequal psychological impact on financial workers and
      lawyers. Financial workers' psychosocial work stress and burnout were aggravated,
      while lawyers' psychosocial work stress and burnout were alleviated.

PMID- 21190033
TI  - Describing individual variation in local sweating during exercise in a temperate
      environment.
AB  - It has been previously demonstrated that the individual variation in whole-body
      sweat rate is described by differences in each participant's heat balance status.
      It was hypothesized that the individual variation in local sweat rate of the
      forehead (LSR(head)) and forearm (LSR(arm)) would be similarly described using a
      whole-body heat balance approach, specifically the ratio of evaporation required
      for heat balance relative to the maximum evaporation possible (i.e. E (req):E
      (max)). Twelve males cycled at 60% [Formula: see text] for 60 min at 24.9 +/- 0.5
      degrees C, 31 +/- 14% relative humidity. Rectal (T (re)) and aural canal (T (au))
      temperatures as well as mean skin temperature ([Formula: see text]), metabolic
      energy expenditure (M) and rate of external work (W) were measured throughout. In
      addition, whole-body sweat rate at steady state (WBSR(ss)) was estimated using
      the change in body mass over the last 15 min of exercise, with LSR(head) and
      LSR(arm) estimated using technical absorbent patches applied between the 50th and
      55th minute. WBSR(ss) significantly correlated with M-W (r = 0.66, P = 0.021), E
      (req) (r = 0.69, P = 0.013) and E (req):E (max) (r = 0.87, P < 0.001); LSR(head)
      was significantly correlated with E (req):E (max) (r = 0.82, P = 0.001), but not
      M-W (r = 0.31, P = 0.328) or E (req) (r = 0.38, P = 0.227); and LSR(arm)
      significantly correlated with E (req) (r = 0.62, P = 0.031) and E (req):E (max)
      (r = 0.78, P = 0.003) but not M-W (r = 0.56, P = 0.059). None of WBSR(ss),
      LSR(head) or LSR(arm) significantly correlated with any variations in T (re), T
      (au) or [Formula: see text] (i.e. 0.8T (re) + 0.2[Formula: see text]). Secondary
      analyses also demonstrated that both LSR(head) (r = 0.79, P = 0.002) and LSR(arm)
      (r = 0.89, P < 0.001) correlated with WBSR(ss). In conclusion, the individual
      variation in WBSR(ss), LSR(head) and LSR(arm) is described by the ratio of E
      (req) relative to E (max).

PMID- 21190034
TI  - On the method of fitting cardiac output kinetics in severe exercise.
AB  - The kinetic responses of oxygen uptake (VO2) and cardiac output (Q) describe the
      rate at which these physiological variables approach the required steady state
      value with work rate transitions. In this issue of the Journal, Adami and
      colleagues examined the kinetic responses during the transition to severe
      intensity exercise (metabolic demands exceeding maximal VO2). Two methods were
      described for fitting VO2 kinetics: one was an exponential model that referenced
      the time course of VO2 relative to an apparent plateau while the second examined
      the rate of change with respect to the value predicted to be 120% of maximal VO2.
      The rate of change of the primary adaptive component described by the time
      constant (tau2) was considerably slower when referenced to the predicted VO2
      (62.5 s) than when fit by the exponential model (20.3 s). For the description of
      Q kinetics Adami and colleagues fitted only the exponential model. We
      investigated the impact of fitting the kinetics of Q relative to a predicted
      value for this severe work rate as was done for VO2. The time course for Q was
      reconstructed from their group mean fitting parameters then referenced to values
      for the required Q based on the literature. The estimate for the time constant
      (tau2) exceeded the value determined from the exponential model in which the
      curve fit was referenced to an apparent plateau by more than sixfold (86.4 s vs.
      13.5 s). This outcome suggests that future investigations should explore further
      the dynamic interactions of metabolic regulatory factors and the limitations of
      the O2 supply system when describing the system kinetics.

PMID- 21190035
TI  - Oxygen uptake, cardiac output and muscle deoxygenation at the onset of moderate
      and supramaximal exercise in humans.
AB  - VO2, Q and muscular deoxyhaemoglobin (HHb) kinetics were determined in 14 healthy
      male subjects at the onset of constant-load cycling exercise performed at 80% of
      the ventilatory threshold (80%(VT)) and at 120% of VO2max (120%(Wmax)). An
      innovative approach was applied to calculate the time constant (tau2) of the
      primary phase of VO2 and Q kinetics at 120%(Wmax). Data were linearly
      interpolated after a semilogarithmic transformation of the difference between
      required/steady state and measured values. Furthermore, VO2, Q and HHb data were
      fitted with traditional exponential models. tau2 of VO2 kinetics was longer (62.5
      +/- 20.9 s) at 120%(Wmax) than at 80%(VT) (27.8 +/- 10.4 s). The tau2 of Q
      kinetics was unaffected by exercise intensity and, at 120% of VO2max, it was
      significantly faster (tau2 = 35.7 +/- 28.4 s) than that of VO2 response. The time
      delay of HHb kinetics was shorter (4.3 +/- 1.7 s) at 120%(Wmax) than at 80%(VT)
      (8.5 +/- 2.6 s) suggesting a larger mismatch between O2 uptake and delivery at
      120%(Wmax). These results suggest that VO2 at the onset of exercise is not
      regulated/limited by muscle's O2 utilisation and that a slower adaptation of
      capillary perfusion may cause the deceleration of VO2 kinetics observed during
      supramaximal exercise.

PMID- 21190036
TI  - Effect of sprint interval training on circulatory function during exercise in
      sedentary, overweight/obese women.
AB  - Very high-intensity, low-volume, sprint interval training (SIT) increases muscle
      oxidative capacity and may increase maximal oxygen uptake ([Formula: see text]),
      but whether circulatory function is improved, and whether SIT is feasible in
      overweight/obese women is unknown. To examine the effects of SIT on [Formula: see
      text] and circulatory function in sedentary, overweight/obese women. Twenty-eight
      women with BMI > 25 were randomly assigned to SIT or control (CON) groups. One
      week before pre-testing, subjects were familarized to [Formula: see text] testing
      and the workload that elicited 50% [Formula: see text] was calculated. Pre- and
      post-intervention, circulatory function was measured at 50% of the pre
      intervention [Formula: see text], and a GXT was performed to determine [Formula:
      see text]. During the intervention, SIT training was given for 3 days/week for 4
      weeks. Training consisted of 4-7, 30-s sprints on a stationary cycle (5% body
      mass as resistance) with 4 min active recovery between sprints. CON maintained
      baseline physical activity. Post-intervention, heart rate (HR) was significantly
      lower and stroke volume (SV) significantly higher in SIT (-8.1 and 11.4%,
      respectively; P < 0.05) during cycling at 50% [Formula: see text]; changes in CON
      were not significant (3 and -4%, respectively). Changes in cardiac output
      ([Formula: see text]) and arteriovenous oxygen content difference [(a - v)O(2)
      diff] were not significantly different for SIT or CON. The increase in [Formula:
      see text] by SIT was significantly greater than by CON (12 vs. -1%). Changes by
      SIT and CON in HR(max) (-1 vs. -1%) were not significantly different. Four weeks
      of SIT improve circulatory function during submaximal exercise and increases
      [Formula: see text] in sedentary, overweight/obese women.

PMID- 21190037
TI  - The effect of different first 200-m pacing strategies on blood lactate and
      biomechanical parameters of the 400-m sprint.
AB  - The purpose of the present study was to evaluate the effect of three pacing
      strategies upon performance of the 400-m sprint. Eight healthy male physical
      education students participated in this study. Each participant performed a 200-m
      maximal test (200(MAX)) and three 400-m running tests in a random counterbalanced
      design. The 400-m tests were run with the first 200-m pace set at 98% (400(98%)),
      95% (400(95%)), and 93% (400(93%)), respectively, of the effort for 200(MAX). The
      stimulation of the lactate system was assessed by post-test blood lactate
      concentration (BLa). Running speed (RS) was controlled with time-keeping devices.
      Stride frequency (SF), stride length (SL) and lower extremity kinematics were
      acquired with video cameras operating at 100 fps at the 125 and 380-m marks of
      the tests. A two-way analysis of variance (ANOVA) with repeated measures was used
      to identify modifications caused by the pacing strategies used. Non-significant
      differences were revealed for BLa. The fastest 400-m race was run in 400(93%),
      but performance was not significantly different (p > 0.05) among the examined
      pacing strategies. RS, SF and SL had significantly (p < 0.05) lower values in the
      380-m mark when compared with the 125-m mark. In 400(98%), both SF and SL
      decreased by approximately 13%, while SF and SL dropped 2.4 and 9.2%,
      respectively, in 400(93%). In conclusion, lower peak BLa and less unfavorable
      modifications of running mechanics were recorded in 400(93%), where time
      differential between the halves of the 400-m race was smaller, which eventually
      resulted in better performance.

PMID- 21190038
TI  - Transcervical video-assisted thymectomy: preliminary results of a modified
      surgical approach.
AB  - PURPOSE: A number of surgical approaches have been reported for thymectomy,
      including transsternal, transcervical, a combination of complete transsternal and
      transcervical, and various video-assisted thoracoscopic surgery techniques. A
      modified video-assisted transcervical approach to thymectomy is here described.
      METHODS: A video-assisted total thymectomy was performed through a 30-mm cervical
      incision. No hyperextension of the patient's neck or sternal retractor was used.
      The surgical instruments utilized for the resection were the ones created for the
      minimally invasive video-assisted thyroidectomy. RESULTS: Five patients have been
      operated on so far. The encapsulated gland was removed without any difficulties.
      No complications occurred. No pain relief was administered after the first 24 h.
      The patients were discharged within the first two postoperative days. An
      improvement in clinical symptoms was registered in all patients. CONCLUSIONS: An
      advantage of this minimally invasive video-assisted transcervical approach to
      thymectomy is that the entire operation can be performed without neck
      hyperextension or permanent sternum elevation. Moreover, the surgical instruments
      created for minimally invasive video-assisted thyroidectomy enabled us to be very
      precise and to complete the resection without any postoperative morbidity.

PMID- 21190039
TI  - Educational paper. The development of new therapies for pediatric oncology.
AB  - Although cure rates for children with cancer are approximately 70%, improvements
      in cure rates have slowed in the past decade, likely due to our inability to
      further improve outcome using currently available drugs. Novel drug approaches
      are needed for children with difficult-to-treat malignancies, such as stage IV
      neuroblastoma, sarcomas, brain tumors, and relapsed leukemia. Several novel
      agents show promise for improving outcome in patients with either high risk or
      recurrent disease. For leukemia, inhibitors of cell cycle progression, such as
      clofarabine and nelarabine, have shown great promise in their ability to increase
      treatment efficacy in high-risk disease. Targeted agents such as tyrosine kinase
      inhibitors, DNA binding compounds (trabectedin), and monoclonal antibodies (GD2
      inhibitors for neuroblastoma and anti-CD22 antibodies for pre-B acute lymphocytic
      leukemia (ALL)) also show promise for future treatment. Extensive reviews of each
      of these agents are presented elsewhere; this article provides an overview of
      molecular agents at different stages of FDA/EMA approval; those that are
      currently approved for use in children, currently approved for use in adults, as
      well as those that show promise in early clinical trial testing, or are supported
      by strong preclinical data.

PMID- 21190040
TI  - Clinical practice: surgical approaches to urolithiasis in children.
AB  - The incidence of urolithiasis in children is increasing. Adequate knowledge of
      treatment modalities and surgical options is therefore essential for every
      pediatrician. Surgical approaches to urolithiasis in children continue to evolve
      with advancements in technology and sophistication of current equipment and
      techniques. Perhaps the most significant development in new techniques is the
      advent of robotic-assisted laparoscopy. This review, for the general
      pediatrician, summarizes the most recent pediatric data and guidelines for
      surgical approaches to treatment of urolithiasis.

PMID- 21190041
TI  - High prevalence of Capillaria plica infections in red foxes (Vulpes vulpes) in
      Southern Germany.
AB  - The nematode Capillaria plica is an ubiquitous parasite of the urinary tract of
      Canidae and Felidae. It causes a wide spectrum of clinical symptoms, ranging from
      asymptomatic infections to urinary bladder inflammation, pollacisuria, dysuria,
      and hematuria. Foxes serve as reservoir hosts and are considered to be a
      potential source of infection for companion and hunting dogs as well as domestic
      cats which acquire the infection by ingestion of earthworms which are the
      intermediate hosts. Despite its importance, epidemiological studies on this
      parasite are scarce and almost entirely lacking altogether for Central Europe.
      Therefore, we examined 116 red foxes (Vulpes vulpes) for the infection of C.
      plica by pathologic examination of the urinary bladders and microscopy of mucosal
      smears and urine sediments. The parasite was detected in 90 (78%; 95% CI, 68.9
      84.8%) of the foxes, originating from all administrative districts of Bavaria
      (Southern Germany). Since Bavaria is characterized by a high number of forests
      and wildlife sanctuaries that provide ideal living conditions for foxes, the
      corresponding risk of infection of companion and hunting dogs by oral ingestion
      of earthworms as the intermediate hosts can likewise not be excluded. Because of
      the scarcity of reports on prevalences of C. plica worldwide, we also include a
      brief review of the available literature.

PMID- 21190042
TI  - Flight metabolic rate has contrasting effects on dispersal in the two sexes of
      the Glanville fritillary butterfly.
AB  - Evolution of dispersal is affected by context-specific costs and benefits. One
      example is sex-biased dispersal in mammals and birds. While many such patterns
      have been described, the underlying mechanisms are poorly understood. Here, we
      study genetic and phenotypic traits that affect butterfly flight capacity and
      examine how these traits are related to dispersal in male and female Glanville
      fritillary butterflies (Melitaea cinxia). We performed two mark-recapture
      experiments to examine the associations of individuals' peak flight metabolic
      rate (MR(peak)) and Pgi genotype with their dispersal in the field. In a third
      experiment, we studied tethered flight in the laboratory. MR(peak) was negatively
      correlated with dispersal distance in males but the trend was positive in
      females, and the interaction between MR(peak) and sex was significant for long
      distance dispersal. A similar but nonsignificant trend was found in relation to
      molecular variation at Pgi, which encodes a glycolytic enzyme: the genotype
      associated with high MR(peak) tended to be less dispersive in males but more
      dispersive in females. The same pattern was repeated in the tethered flight
      experiment: the relationship between MR(peak) and flight duration was positive in
      females but negative in males. These results suggest that females with high
      flight capacity are superior in among-population dispersal, which facilitates the
      spatial spreading of their reproductive effort. In contrast, males with high
      flight capacity may express territorial behaviour, and thereby increase the
      number of matings, whereas inferior males may be forced to disperse. Thus, flight
      capacity has opposite associations with dispersal rate in the two sexes.

PMID- 21190043
TI  - Renal function in pediatric cystic fibrosis patients in the first decade of life.
AB  - With increasing life expectancy and the need for lung transplantation in the
      cystic fibrosis (CF) population, there are increasing reports of chronic kidney
      disease (CKD). However, values for baseline or longitudinal glomerular filtration
      rate (GFR) as measured by exogenous clearance markers are lacking in this
      population. Retrospective cross-sectional study in 2 to 18-year-olds cared for at
      a single CF center who had a GFR measured by plasma disappearance of Technetium
      99 m diethylenetriaminepentaacetic acid (mGFR). The primary outcome was evidence
      of renal dysfunction as defined by CKD stage II or below (mGFR <90 ml/min/1.73
      m(2), persistent abnormalities in urinary sediment, abnormal renal imaging). Of
      63 patients evaluated, four had apparent renal dysfunction, one demonstrated
      decreased mGFR, and three others had persistent microscopic hematuria. The mean
      mGFR was substantially higher (140 +/- 24 ml/min/1.73 m(2)) than expected or
      previously reported for healthy children. We did not demonstrate the presence of
      significant renal impairment after limited aminoglycoside exposure in the first
      decade following diagnosis with CF. However, we did document the presence of
      glomerular hyperfiltration in a significant proportion of our CF patients.

PMID- 21190044
TI  - Clinical significance of cerebrospinal fluid nitric oxide concentrations in
      degenerative cervical and lumbar diseases.
AB  - In animal models of degenerative lumbar disease, inducible nitric oxide synthase
      (iNOS) is expressed in macrophages and Schwann cells following compression of the
      cauda equina. We previously reported that NO metabolites (nitrite plus nitrate:
      [NOx]) in the cerebrospinal fluid (CSF) correlate with postoperative pain relief
      in patients with degenerative lumbar disease and with neurologic recovery rate
      postoperatively or after conservative treatment in patients with spinal cord
      injury. The objective of the present study was to examine the relationship
      between [NOx] and neurologic severity, and recovery in degenerative cervical and
      lumbar diseases. Two hundred fifty-seven cases, including 85 patients with
      cervical compression myelopathy (CCM), 25 with cervical disc herniation (CDH), 70
      with lumbar canal stenosis (LCS), and 77 with lumbar disc herniation (LDH), were
      examined. The CSF [NOx] was measured using the Griess method. Severity of
      neurologic impairment and clinical recovery was assessed using the Japanese
      Orthopedic Association score and Hirabayashi's method. [NOx] in CCM and LCS, but
      not CDH and LDH groups, was significantly higher than that in controls, and
      correlated with postoperative recovery rates, but not with preoperative
      neurologic severity. [NOx] significantly correlated with neurologic recovery
      following surgery for CCM and LCS.

PMID- 21190045
TI  - Prevalence of sleep disturbance in patients with low back pain.
AB  - Low back pain (LBP) is a common health condition that is often associated with
      disability, psychological distress and work loss. Worldwide, billions of dollars
      are expended each year trying to manage LBP, often with limited success.
      Recently, some researchers have reported that LBP patients also report sleep
      disturbance as a result of their LBP. However, as most of this evidence was
      obtained from highly selected groups of patients or from studies with small
      samples, high quality data on prevalence of sleep disturbance for patients with
      LBP are lacking. It is also unclear whether sleep disturbance is more likely to
      be reported by patients with recent-onset LBP than by patients with persistent
      LBP. Finally, it is not known whether high pain intensity, the most relevant
      condition-specific variable, is associated with higher rates of reported sleep
      disturbance. The present study aimed to determine the prevalence of reported
      sleep disturbance in patients with LBP. In addition, we aimed to determine
      whether sleep disturbance was associated with the duration of back pain symptoms
      and whether pain intensity was associated with reported sleep disturbance. Data
      from 1,941 patients obtained from 13 studies conducted by the authors or their
      colleagues between 2001 and 2009 were used to determine the prevalence of sleep
      disturbance. Logistic regression analyses explored associations between sleep
      disturbance, the duration of low back symptoms and pain intensity. The estimated
      prevalence of sleep disturbance was 58.7% (95% CI 56.4-60.7%). Sleep disturbance
      was found to be dependent on pain intensity, where each increase by one point on
      a ten-point visual analogue scale (VAS) was associated with a 10% increase in the
      likelihood of reporting sleep disturbance. Our findings indicate that sleep
      disturbance is common in patients with LBP. In addition, we found that the
      intensity of back pain was only weakly associated with sleep disturbance,
      suggesting that other factors contribute to sleep problems for LBP patients.

PMID- 21190046
TI  - Association between resistin gene -420 C/G polymorphism and the risk of type 2
      diabetes mellitus: a meta-analysis.
AB  - Epidemiological studies on the association between the single nucleotide
      polymorphism (SNP) at -420 C/G (rs1862513) in the human resistin gene (RETN) and
      the risk of type 2 diabetes mellitus (T2DM) are conflicting. In order to derive a
      more precise estimation of the association, a meta-analysis was conducted. Twelve
      studies with 5,935 cases and 5,959 controls were enrolled by searching the
      databases of Medline, EMBASE, and Cochrane. Summary odds ratios (ORs) with 95%
      confidence intervals (CIs) were calculated. The heterogeneity and publication
      bias were investigated. The main analysis indicated no significant association
      [for allelic model: OR = 0.97 (0.92-1.03); for additive model: OR = 0.95 (0.83
      1.09); for recessive model: OR = 0.98 (0.86-1.12); for dominant model: OR = 0.95
      (0.88-1.04)]. Overall, no significant heterogeneity was found. Subgroup analysis
      by race and source of controls indicated no significant association. In
      conclusion, the current meta-analysis did not observe any association between the
      polymorphism of RETN -420 C/G and the risk of T2DM. The study may help us further
      understand the genetics of T2DM. However, larger and prospective studies are
      warranted to confirm this finding.

PMID- 21190047
TI  - Substantia nigra hyperechogenicity is a risk marker of Parkinson's disease: no.
AB  - During the past two decades, transcranial sonography (TCS) has developed to an
      increasingly used brain imaging method that visualizes characteristic patterns of
      basal ganglia alterations in distinct movement disorders. Since the discovery of
      a characteristic abnormal hyperechogenic appearance of substantia nigra (SN) on
      TCS in Parkinson's disease (PD), which is stable during the course of the disease
      and probably present already in preclinical disease stages, the results of
      several studies have promoted the idea that this TCS finding in healthy subjects
      might be a risk marker of PD. The present view summarizes current scientific
      evidence favouring the idea that the TCS finding of SN hyperechogenicity alone
      may not be a (strong) risk marker of PD. Especially, it is discussed how reliable
      this TCS finding is, whether this TCS finding can be regarded as a progression
      marker or a risk marker of PD, how strongly it may indicate a risk of PD, what
      else if not an increased risk of PD could be indicated, and which role TCS of SN
      may finally play in the detection of subjects at risk of PD.

PMID- 21190048
TI  - Identification of the copper-binding ligands of lysyl oxidase.
AB  - In order to identify the ligands coordinating with copper in lysyl oxidase, the
      enzyme was expressed in an E. coli expression system and active enzyme obtained
      after refolding in the presence of Cu(II). The five histidines found in the
      putative copper-binding region were sequentially mutated to alanines and the
      enzymatic activities of the resultant mutants were monitored, together with the
      copper content, the CD and fluorescence spectra, and the redox-cycling activity.
      The spectroscopic results show that in all cases the protein folded correctly but
      that the copper-content, enzymatic activity, and redox-cycling ability depended
      on the mutation. One mutant was fully functional, and two others completely
      lacked copper, the lysyl tyrosyl quinone (LTQ) cofactor, and activity. A fourth
      incorporated copper but lacked LTQ and enzymatic activity. The remaining mutant
      incorporated copper and had redox-cycling activity but no enzymatic activity. The
      results suggest that three of the five histidines in the putative copper-binding
      domain, H292, H294, H296, are the copper ligands and essential to the formation
      of LTQ. A fourth, H289, is not involved in LTQ formation or activity, while a
      fifth, H303, is suggested to be a general base in the catalytic mechanism.

PMID- 21190049
TI  - Thermal hypesthesia in patients with complex regional pain syndrome related
      dystonia.
AB  - The quantitative thermal test showed cold and warmth hypesthesia without
      increased heat pain sensitivity in the affected limbs of complex regional pain
      syndrome (CRPS) patients with tonic dystonia (n = 44) in comparison with healthy
      controls with a similar age and sex distribution (n = 35). The degrees of cold
      and warmth hypesthesia were strongly correlated. We conclude that dysfunction in
      small nerve fiber (i.e., C and Adelta) processing is present in patients with
      CRPS-related dystonia.

PMID- 21190050
TI  - High frequency deep brain stimulation of the subthalamic nucleus versus
      continuous subcutaneous apomorphine infusion therapy: a review.
AB  - In advanced Parkinson's disease, several therapeutical option including not only
      lesional surgery (VIM, GPi) and deep brain stimulation (STN, GPi, VIM) but also
      continuous subcutaneous apomorphine infusion therapy can be proposed to the
      patient. The choice depends on the hope of the patient, patient's general health
      condition and the experience and choice of the neurosurgical and neurologist
      team. Here we report our experience based on 400 STN-DBS cases and we discuss, on
      the basis of our experience and on the literature, the advantage and disadvantage
      of DBS strategy as compared with non-surgical option such as continuous
      subcutaneous apomorphine infusion therapy.

PMID- 21190051
TI  - Influence of brain-derived neurotrophic-factor and apolipoprotein E genetic
      variants on hippocampal volume and memory performance in healthy young adults.
AB  - Unravelling the impact of genetic variants on clinical phenotypes is a
      challenging task. Apolipoprotein E (ApoE) and brain-derived neurotrophic factor
      (BDNF) play an important role in cell growth, regeneration, synaptic plasticity,
      learning and memory processes. The aim of the present study was to examine the
      impact of BDNF Val66Met- and ApoE-polymorphisms and their interactions on
      hippocampal morphology and memory functions in healthy young adults. Hippocampal
      volume and memory performance of 135 healthy individuals, aged 24.6 +/- 3.2
      years, were assessed, using magnetic resonance imaging and the Inventory for
      Memory diagnostics. The performance of BDNF-Met66 carriers was significantly
      lower in working memory (P = 0.03) compared with non carriers, whereas no further
      differences were observed either in cognitive performance or in hippocampal
      volumes between the groups. Age, BDNF Val66 Met polymorphism and the interaction
      factor BDNF genotype x age were significantly associated with the variation of
      working memory scores (P = 0.01, 0.01, 0.02 respectively). No statistically
      significant differences were detected in the volumes of hippocampi and in memory
      phenotypes between individuals carrying the ApoE E4 allele and those without it.
      The analysis did not reveal an impact of gene-gene interaction between BDNF and
      ApoE genes on hippocampal volumes or memory performance. BDNF Val66Met
      polymorphism seems to influence working memory function and modulate the effects
      of ageing on working memory in healthy young adults.

PMID- 21190053
TI  - Teacher reports of hypoactivity symptoms reflect slow cognitive processing speed
      in primary school children.
AB  - The mediating effect of cognitive processing speed on the ability of a primary
      school child to achieve his/her full potential of intellectual functioning
      emphasizes the importance of methods to detect "slow" children. Primary school
      teachers may be the first to have concerns about inattentive pupils who show
      symptoms of hypoactivity, but may find the symptoms difficult to interpret. In
      the present study we ask if a primary school teacher's report of hypoactivity
      symptoms can be explained by the child's performance on tests of processing
      speed. The 255 children included in the present study were part of the first wave
      of the Bergen Child Study, in which teachers completed a questionnaire including
      two hypoactivity items from the Five to Fifteen (FTF) questionnaire. Processing
      speed was measured by the Processing Speed Index (PSI) from the WISC-III, 1-2
      years after the teacher rating. Teachers reported "certainly true" on at least
      one FTF item of hypoactivity for 11.8% of the children. These children obtained
      lower scores on the PSI than the remaining children in the sample. The PSI
      accounted for a considerable proportion of the variance of teacher reports on the
      FTF item "difficulty getting started on a task/activity". The risk of a PSI score
      below 85 was increased in children with teacher-reported hypoactivity symptoms.
      The results indicate that teacher reports of hypoactivity symptoms reflect slow
      cognitive processing speed and should be followed up by a psychometric
      examination. Still, future studies are needed to improve detection and treatment
      of children with slow processing speed.

PMID- 21190052
TI  - Dietary inhibitors of monoamine oxidase A.
AB  - Inhibition of monoamine oxidase is one way to treat depression and anxiety. The
      information now available on the pharmacokinetics of flavonoids and of the
      components of tobacco prompted an exploration of whether a healthy diet (with or
      without smoking) provides active compounds in amounts sufficient to partially
      inhibit monoamine oxidase. A literature search was used to identify dietary
      monoamine oxidase inhibitors, the levels of these compounds in foods, the
      pharmacokinetics of the absorption and distribution, and tissue levels observed.
      An estimated daily intake and the expected tissue concentrations were compared
      with the measured efficacies of the compounds as inhibitors of monoamine
      oxidases. Norharman, harman and quercetin dietary presence, pharmacokinetics, and
      tissue levels were consistent with significant levels reaching neuronal monoamine
      oxidase from the diet or smoking; 1,2,3,4-tetrahydroisoquinoline, eugenol, 1
      piperoylpiperidine, and coumarin were not. Quercetin was equipotent with
      norharman as a monoamine oxidase A inhibitor and its metabolite, isorhamnetin,
      also inhibits. Total quercetin was the highest of the compounds in the sample
      diet. Although bioavailability was variable depending on the source, a healthy
      diet contains amounts of quercetin that might give sufficient amounts in brain to
      induce, by monoamine oxidase A inhibition, a small decrease in neurotransmitter
      breakdown.

PMID- 21190054
TI  - Laser-induced modification of the patellar ligament tissue: comparative study of
      structural and optical changes.
AB  - The effects of non-ablative infrared (IR) laser treatment of collagenous tissue
      have been commonly interpreted in terms of collagen denaturation spread over the
      laser-heated tissue area. In this work, the existing model is refined to account
      for the recently reported laser-treated tissue heterogeneity and complex collagen
      degradation pattern using comprehensive optical imaging and calorimetry toolkits.
      Patella ligament (PL) provided a simple model of type I collagen tissue
      containing its full structural content from triple-helix molecules to gross
      architecture. PL ex vivo was subjected to IR laser treatments (laser spot, 1.6
      mm) of equal dose, where the tissue temperature reached the collagen denaturation
      temperature of 60 +/- 2 degrees C at the laser spot epicenterin the first regime,
      and was limited to 67 +/- 2 degrees C in the second regime. The collagen network
      was analyzed versus distance from the epicenter. Experimental characterization of
      the collagenous tissue at all structural levels included cross-polarization
      optical coherence tomography, nonlinear optical microscopy, light
      microscopy/histology, and differential scanning calorimetry. Regressive
      rearrangement of the PL collagen network was found to spread well outside the
      laser spot epicenter (>2 mm) and was accompanied by multilevel hierarchical
      reorganization of collagen. Four zones of distinct optical and morphological
      properties were identified, all elliptical in shape, and elongated in the
      direction perpendicular to the PL long axis. Although the collagen transformation
      into a random-coil molecular structure was occasionally observed, it was
      mechanical integrity of the supramolecular structures that was primarily
      compromised. We found that the structural rearrangement of the collagen network
      related primarily to the heat-induced thermo-mechanical effects rather than
      molecular unfolding. The current body of evidence supports the notion that the
      supramolecular collagen structure suffered degradation of various degrees, which
      gave rise to the observed zonal character of the laser-treated lesion.

PMID- 21190055
TI  - SOX2 gene expression in normal human thymus and thymoma.
AB  - The SOX gene family encodes a large group of transcription factors that are
      strongly involved in the normal human development and malignancies. Human tumors,
      like small cell lung carcinoma, meningioma, gastric, and pancreatic cancer, have
      been found to be immunogenic for SOX2 protein. In this study, we have
      investigated for the first time the expression and distribution of SOX2
      immunoreactive cells in five normal human thymuses (2 fetal and 3 adult) and 10
      thymomas bioptic specimens. Results demonstrated the presence of few positive
      cells in the fetal and postnatal normal human thymus with a specific distribution
      within thymus parenchyma compartments. On the contrary, in thymoma
      immunoreactivity to SOX2 increased parallel to pathological stage, and a peculiar
      distribution was observed in type B3 thymoma with a positive reaction in both
      tumor and endothelial cells.

PMID- 21190056
TI  - B7-H4 expression in various tumors determined using a novel developed monoclonal
      antibody.
AB  - B7-H4, a new member of the B7 family, may participate in the negative regulation
      of cell-mediated immunity, while aberrant B7-H4 expression is detected in some
      tumors and it participates in the occurrence and development of the tumors. In
      this study, we developed one monoclonal antibody (mAb) whose clone No. was 4H8
      against the extracellular domains of B7-H4 through immunization of Balb/c mice
      with the 3T3-mB7-H4 cells that expressed extrinsic B7-H4 stably. And we detected
      the expression characteristics of B7-H4 in various tumors using 4H8 mAb by enzyme
      linked immunosorbent assay (ELISA), immunoprecipitation and immunohistochemistry
      (IHC) analysis. B7-H4 expression was significantly higher in the tumor tissues
      derived from uterus, breast, and colon than in their corresponding normal
      tissues. Further, the B7-H4 expression was related to the stage of the tumors. In
      contrast, B7-H4 expression did not differ significantly between the tumor tissues
      derived from the stomach and liver and the normal tissues. Different expression
      levels of B7-H4 in the tumors indicated that B7-H4 may be involved in tumor
      formation and development. Specific mAbs against B7-H4 will be useful in studying
      the role of B7-H4 in tumor pathogenesis and pathological process.

PMID- 21190057
TI  - Mining electron density for functionally relevant protein polysterism in crystal
      structures.
AB  - This review focuses on conceptual and methodological advances in our
      understanding and characterization of the conformational heterogeneity of
      proteins. Focusing on X-ray crystallography, we describe how polysterism, the
      interconversion of pre-existing conformational substates, has traditionally been
      analyzed by comparing independent crystal structures or multiple chains within a
      single crystal asymmetric unit. In contrast, recent studies have focused on
      mining electron density maps to reveal previously 'hidden' minor conformational
      substates. Functional tests of the importance of minor states suggest that
      evolutionary selection shapes the entire conformational landscape, including
      uniquely configured conformational substates, the relative distribution of these
      substates, and the speed at which the protein can interconvert between them. An
      increased focus on polysterism may shape the way protein structure and function
      is studied in the coming years.

PMID- 21190059
TI  - Spinal cord anaplastic oligodendroglioma with 1p deletion: report of a relapsing
      case treated with temozolomide.
AB  - Primary spinal cord oligodendroglial tumor is very rare, and in only one patient
      with spinal cord oligodendroglioma has a deletion of chromosome 1p/19q been
      reported. We present the case of an 18-year-old girl, who had one-year lower back
      pain and one-month lower limb weakness. Magnetic resonance images of the spinal
      cord showed an intramedullary mass from level T8 to T10, which was then radically
      removed. Histology revealed an anaplastic oligodendroglioma. The patient was
      treated with radiotherapy postoperatively. Eight months after the treatment,
      follow-up magnetic resonance images disclosed an enhancing intramedullary mass at
      level T4-T8; recurrence of the tumor was therefore diagnosed. Maximum surgical
      removal of the recurrent tumor was performed, diagnosis of anaplastic
      oligodendroglioma was made, and a chromosome 1p deletion was determined by FISH.
      After treatment with temozolomide for six months, the patient had a remarkable
      improvement of her lower limb symptoms, and complete imaging regression of the
      residual tumor showed no evidence of recurrence at any other sites. The most
      recent MRI of brain and spinal cord showed postoperative changes without evidence
      of tumor recurrence of the spine and oligodendrogliomatosis along the cerebral
      spinal axis. To our knowledge, this is the first report of a recurrent anaplastic
      oligodendroglioma with 1p deletion occurring in the spinal cord. It is also the
      first case of the patient with recurrent intramedullary anaplastic
      oligodendroglioma who had a significant clinical improvement and complete imaging
      remission after subtotal resection then treatment with temozolomide chemotherapy.

PMID- 21190058
TI  - Technologies of directed protein evolution in vivo.
AB  - Directed evolution of proteins for improved or modified functionality is an
      important branch of modern biotechnology. It has traditionally been performed
      using various in vitro methods, but more recently, methods of in vivo artificial
      evolution come into play. In this review, we discuss and compare prokaryotic and
      eukaryotic-based systems of directed protein evolution in vivo, highlighting
      their benefits and current limitations and focusing on the biotechnological
      potential of vertebrate immune cells for the generation of protein diversity by
      means of the immunoglobulin diversification machinery.

PMID- 21190060
TI  - Saturation mutagenesis of Acremonium chrysogenum deacetoxy/deacetylcephalosporin
      C synthase R308 site confirms its role in controlling substrate specificity.
AB  - Deacetoxy/deacetylcephalosporin C synthase (acDAOC/DACS) from Acremonium
      chrysogenum is a bifunctional enzyme that catalyzes both the ring-expansion of
      penicillin N to deacetoxycephalosporin C and the hydroxylation of the latter to
      deacetylcephalosporin C. The R308 residue located in close proximity to the C
      terminus of acDAOC/DACS was mutated to the other 19 amino acids. In the resulting
      mutant pool, R308L, R308I, R308T and R308V showed significant improvement in
      their ability to convert penicillin analogs, thus confirming the role of R308 in
      controlling substrate selectivity, the four amino acids all possess short
      aliphatic sidechains that may improve hydrophobic interactions with the
      substrates. The mutant R308I showed the highest reactivity for penicillin G, with
      3-fold increase in k(cat)/K(m) ratio and 7-fold increase in relative activity.

PMID- 21190061
TI  - Celebrating its 20th anniversary in 2011, the Journal of Biomolecular NMR looks
      forward to the second decade of the 21st century.

PMID- 21190062
TI  - Pseudo-4D triple resonance experiments to resolve HN overlap in the backbone
      assignment of unfolded proteins.
AB  - The solution NMR resonance assignment of the protein backbone is most commonly
      carried out using triple resonance experiments that involve (15)N and (1)HN
      resonances. The assignment becomes problematic when there is resonance overlap of
      (15)N-(1)HN cross peaks. For such residues, one cannot unambiguously link the
      "left" side of the NH root to the "right" side, and the residues associated with
      such overlapping HN resonances remain often unassigned. Here we present a
      solution to this problem: a hybrid (4d,3d) reduced-dimensionality HN(CO)CA(CON)CA
      sequence. In this experiment, the Ca(i) resonance is modulated with the frequency
      of the Ca(i-1) resonance, which helps in resolving the ambiguity involved in
      connecting the Ca(i) and Ca(i-1) resonances for overlapping NH roots. The
      experiment has limited sensitivity, and is only suited for small or unfolded
      proteins. In a companion experiment, (4d,3d) reduced-dimensionality HNCO(N)CA,
      the Ca(i) resonance is modulated with the frequency of the CO(i-1) resonance,
      hence resolving the ambiguity existent in pairing up the Ca(i) and CO(i-1)
      resonances for overlapping NH roots.

PMID- 21190063
TI  - Recovering lost magnetization: polarization enhancement in biomolecular NMR.
AB  - Experimental sensitivity remains a major drawback for the application of NMR
      spectroscopy to fragile and low concentrated biomolecular samples. Here we
      describe an efficient polarization enhancement mechanism in longitudinal
      relaxation enhanced fast-pulsing triple-resonance experiments. By recovering
      undetectable (1)H polarization originating from longitudinal relaxation during
      the pulse sequence, the steady-state (15)N polarization becomes enhanced by up to
      a factor of ~5 with respect to thermal equilibrium yielding significant
      sensitivity improvements compared to conventional schemes. The benefits of BEST
      TROSY experiments at high magnetic field strength are illustrated for various
      protein applications, but they will be equally useful for other protonated
      macromolecular systems.

PMID- 21190064
TI  - Recognition of A. thaliana centromeres by heterologous CENH3 requires high
      similarity to the endogenous protein.
AB  - The centromere is an essential chromosomal component assembling the kinetochore
      for chromosome attachment to the spindle microtubules and for directing the
      chromosome segregation during nuclear division. Kinetochore assembly requires
      deposition of the centromeric histone H3 variant (CENH3) into centromeric
      nucleosomes. CENH3 has a variable N-terminal and a more conserved C-terminal
      part, including the loop1 region of the histone fold domain, which is considered
      to be critical for centromere targeting. To investigate the structural
      requirements for centromere targeting, constructs for EYFP-tagged CENH3 of A.
      lyrata, A. arenosa, Capsella bursa-pastoris, Zea mays and Luzula nivea (the
      latter with holocentric chromosomes) were transformed into A. thaliana. Except
      for LnCENH3, all recombinant CENH3 proteins targeted A. thaliana centromeres, but
      the more distantly related the heterologous protein is, the lower is the
      efficiency of targeting. Alignment of CENH3 sequences revealed that the tested
      species share only three amino acids at loop1 region: threonine2, arginine12 and
      alanine15. These three amino acids were substituted by asparagine, proline and
      valine encoding sequences within a recombinant EYFP-AtCENH3 construct via PCR
      mutagenesis prior to transformation of A. thaliana. After transformation,
      immunostaining of root tip nuclei with anti-GFP antibodies yielded only diffuse
      signals, indicating that the original three amino acids are necessary but not
      sufficient for targeting A. thaliana centromeres.

PMID- 21190065
TI  - Rapid evolution of osmoregulatory function by modification of gene transcription
      in steelhead trout.
AB  - Populations experiencing sudden environmental change must be capable of rapidly
      evolving to survive. Here we explore changes in gene transcription as a mechanism
      for rapid adaptation at four osmoregulatory genes (CFTR I, NaK ATPase1alphaa, NaK
      ATPase1alphab and GHRII) in anadromous steelhead trout versus a derived land
      locked population after 14 generations. Transcription was measured before and
      after a 24-h saltwater challenge in pure and reciprocal hybrid offspring of fish
      from both populations reared in a common environment for two generations.
      Significant differences between the landlocked and migratory populations were
      observed, particularly in fresh water at the NaK ATPase1alphaa and GHRII genes,
      indicating rapid evolutionary change, possibly associated with reduced energy
      expenditure in the landlocked lake system. Phenotypic divergence analysis (Q
      (ST)) shows that the observed transcriptional differences deviate from neutral
      expectations. Some reciprocal crosses exhibited anomalous transcription
      consistent with sex-linked epistatic or genetic imprinting effects. Our results
      highlight unpredictable phenotypic outcomes of hybridization among locally
      adapted populations and the need to exercise caution when interbreeding
      populations for conservation purposes.

PMID- 21190066
TI  - An RNA Phage Lab: MS2 in Walter Fiers' laboratory of molecular biology in Ghent,
      from genetic code to gene and genome, 1963-1976.
AB  - The importance of viruses as model organisms is well-established in molecular
      biology and Max Delbruck's phage group set standards in the DNA phage field. In
      this paper, I argue that RNA phages, discovered in the 1960s, were also
      instrumental in the making of molecular biology. As part of experimental systems,
      RNA phages stood for messenger RNA (mRNA), genes and genome. RNA was thought to
      mediate information transfers between DNA and proteins. Furthermore, RNA was more
      manageable at the bench than DNA due to the availability of specific RNases,
      enzymes used as chemical tools to analyse RNA. Finally, RNA phages provided
      scientists with a pure source of mRNA to investigate the genetic code, genes and
      even a genome sequence. This paper focuses on Walter Fiers' laboratory at Ghent
      University (Belgium) and their work on the RNA phage MS2. When setting up his
      Laboratory of Molecular Biology, Fiers planned a comprehensive study of the virus
      with a strong emphasis on the issue of structure. In his lab, RNA sequencing, now
      a little-known technique, evolved gradually from a means to solve the genetic
      code, to a tool for completing the first genome sequence. Thus, I follow the
      research pathway of Fiers and his 'RNA phage lab' with their evolving
      experimental system from 1960 to the late 1970s. This study illuminates two
      decisive shifts in post-war biology: the emergence of molecular biology as a
      discipline in the 1960s in Europe and of genomics in the 1990s.

PMID- 21190067
TI  - Influence of acylation on the adsorption of insulin to hydrophobic surfaces.
AB  - PURPOSE: To study the effect of acylation on the adsorption of insulin to
      hydrophobic polystyrene beads. METHODS: Adsorption isotherms for adsorption of
      insulin and acylated insulin to hydrophobic polystyrene beads were established,
      and the adsorption of the two proteins was compared further with isothermal
      titration calorimetry. In addition, the secondary structure and the association
      behavior of the two proteins were studied with circular dichroism. RESULTS:
      Insulin and acylated insulin adsorbed with high affinity to the hydrophobic
      polystyrene beads. More acylated insulin molecules than insulin molecules
      adsorbed per unit surface area from solutions containing monomer-dimer mixtures
      of acylated insulin and insulin, respectively. In contrast, no difference was
      observed in the number of insulin and acylated insulin molecules adsorbing per
      unit surface area, when adsorption occurred from solutions containing monomer
      dimer-hexamer mixtures. CONCLUSION: The influence of acylation on the adsorption
      behavior of insulin depends on the association degree of insulin, possibly due to
      a greater difference in hydrophobicity between monomeric insulin and acylated
      insulin than between the hexameric forms of these two proteins.

PMID- 21190068
TI  - Millennial medical anthropology: from there to here and beyond, or the problem of
      global health.
AB  - While much of Medical Anthropology was and is what we can call "Normal"
      (following Kuhn) Medical Anthropology, I coined the term Millennial Medical
      Anthropology for that branch of the discipline that, in the 1990s, was departing
      from the Normal research paradigms and was deserving of a distinct sobriquet.
      This paper considers the Strong Program in Medical Anthropology's Millennial
      Medical Anthropology and its key subdivisions, the Cultural Studies of Science
      and Cultural Bioethics. Specifically it considers Medical Anthropology's movement
      from the past into an ethical future wherein Normal Biomedicine, Bioethics and
      Global Health are problematized. This provides the basis for the construction of
      a truly anthropological global health (i.e., Global, Global Health or Global
      Health 2.0).

PMID- 21190069
TI  - Reproducing hegemony: the culture of enhancement and discourses on amphetamines
      in popular fiction.

PMID- 21190070
TI  - The racial disparity in breast cancer mortality.
AB  - Black women die of breast cancer at a much higher rate than white women. Recent
      studies have suggested that this racial disparity might be even greater in
      Chicago than the country as a whole. When data describing this racial disparity
      are presented they are sometimes attributed in part to racial differences in
      tumor biology. Vital records data were employed to calculate age-adjusted breast
      cancer mortality rates for women in Chicago, New York City and the United States
      from 1980-2005. Race-specific rate ratios were used to measure the disparity in
      breast cancer mortality. Breast cancer mortality rates by race are the main
      outcome. In all three geographies the rate ratios were approximately equal in
      1980 and stayed that way until the early 1990s, when the white rates started to
      decline while the black rates remained rather constant. By 2005 the black:white
      rate ratio was 1.36 in NYC, 1.38 in the US, and 1.98 in Chicago. In any number of
      ways these data are inconsistent with the notion that the disparity in
      black:white breast cancer mortality rates is a function of differential biology.
      Three societal hypotheses are posited that may explain this disparity. All three
      are actionable, beginning today.

PMID- 21190071
TI  - Factors associated with perceived susceptibility to cervical cancer among Latina
      immigrants in Alabama.
AB  - To examine factors associated with perceived susceptibility to cervical cancer
      among Latina immigrants in two counties in Alabama. Datasets from two anonymous
      cross-sectional surveys from two studies were combined for these analyses. The
      total sample size was 743 women. Participants' average age was 30 +/- 6.8 years
      and they were mainly from Mexico (89.2%). Almost 36% of the participants did not
      perceive themselves as being susceptible to cervical cancer, 33.9% did not know
      if they were susceptible, and 30.4% perceived themselves as susceptible.
      Educational attainment, thinking they may have been exposed to an STI in the
      past, thinking they may be at risk of HPV currently, having had a Pap smear
      within the last year, and having a relative with cancer were significantly
      associated with perceived susceptibility to cervical cancer in the multinomial
      logistic regression. Greater knowledge about cervical cancer risk factors reduced
      the uncertainty about perceived susceptibility. Perceived susceptibility to
      cervical cancer seems to be influenced more importantly by the current or past
      perception of HPV/STI exposure, and by having a relative with cancer. This
      finding is critical in the development of interventions that are tailored to
      Latina immigrants as well as efforts to educate providers in a state where Latino
      immigration is a recent phenomenon.

PMID- 21190072
TI  - HIV seroprevalence among high-risk groups in Kohgiloyeh and Boyerahmad Province,
      Southwest of Iran, a behavioral surveillance survey.
AB  - We conducted a survey to assess the seroprevalence and risk behaviors for HIV
      infection in 2,009 individuals in Kohgiloyeh and Boyerahmad province, in
      Southwest of Iran. Blood samples were drawn from each participant and tested for
      anti-HIV1/2 antibodies. HIV antibodies were detected in 36 (1.8%) blood samples
      among a total of 2,009 participants. The rate of infection in inmates was 2.7%
      while this rate was 9.9% in injection drug users. Correlation between HIV
      infection and sex, age, marital status, history of imprisonment, injection drug
      use, and place of residence were significant. Improving of the surveillance in
      this community through supervision and monitoring of infected people is needed.

PMID- 21190073
TI  - Methamphetamine use, transmission risk behavior and internet use among HIV
      infected patients in medical care, San Francisco, 2008.
AB  - Methamphetamine use is associated with adverse health outcomes and HIV incidence.
      Few studies have assessed methamphetamine use, sexual behavior and Internet use
      among HIV-infected patients. Surveys were administered to a sample of HIV
      infected patients seeking medical care in a San Francisco county hospital and
      university-based clinic. In 2008, 35% of homosexual participants, 26% of
      heterosexual participants and 11% of female participants reported methamphetamine
      use in the past year. Of participants, 29% reported using the Internet to find
      sex partners; Internet-users versus non-Internet-users reported a higher median
      number of sex partners in 6 months (4 vs. 1), were more likely to report
      unprotected sex (32 vs. 10%), and higher rates of methamphetamine use in the past
      12 months (48 vs. 24%). Given the association among methamphetamine use,
      increased sex partners and Internet use, the Internet may present a new and
      effective medium for interventions to reduce methamphetamine-associated sexual
      risk behavior.

PMID- 21190074
TI  - Concurrent partnerships, acute infection and HIV epidemic dynamics among young
      adults in Zimbabwe.
AB  - This paper explores the roles of acute infection and concurrent partnerships in
      HIV transmission dynamics among young adults in Zimbabwe using realistic
      representations of the partnership network and all published estimates of stage
      specific infectivity. We use dynamic exponential random graph models to estimate
      partnership network parameters from an empirical study of sexual behavior and
      drive a stochastic simulation of HIV transmission through this dynamic network.
      Our simulated networks match observed frequencies and durations of short- and
      long-term partnerships, with concurrency patterns specific to gender and
      partnership type. Our findings suggest that, at current behavior levels, the
      epidemic cannot be sustained in this population without both concurrency and
      acute infection; removing either brings transmission below the threshold for
      persistence. With both present, we estimate 20-25% of transmissions stem from
      acute-stage infections, 30-50% from chronic-stage, and 30-45% from AIDS-stage.
      The impact of acute infection is strongly moderated by concurrency. Reducing this
      impact by reducing concurrency could potentially end the current HIV epidemic in
      Zimbabwe.

PMID- 21190075
TI  - Developing the mental health workforce: review and application of training
      approaches from multiple disciplines.
AB  - Strategies specifically designed to facilitate the training of mental health
      practitioners in evidence-based practices (EBPs) have lagged behind the
      development of the interventions themselves. The current paper draws from an
      interdisciplinary literature (including medical training, adult education, and
      teacher training) to identify useful training and support approaches as well as
      important conceptual frameworks that may be applied to training in mental health.
      Theory and research findings are reviewed, which highlight the importance of
      continued consultation/support following training workshops, congruence between
      the training content and practitioner experience, and focus on motivational
      issues. In addition, six individual approaches are presented with careful
      attention to their empirical foundations and potential applications. Common
      techniques are highlighted and applications and future directions for mental
      health workforce training and research are discussed.

PMID- 21190076
TI  - Effect of the PARP-1 inhibitor PJ 34 on excitotoxic damage evoked by kainate on
      rat spinal cord organotypic slices.
AB  - Excitotoxicity triggered by over-activation of glutamate receptors is thought to
      be an early mechanism of extensive neuronal death with consequent loss of
      function following lesion of spinal networks. One important process responsible
      for excitotoxic death is 'parthanatos' caused by hyperactivation of poly(ADP
      ribose) polymerase (PARP) enzyme 1. Using rat organotypic spinal slices as in
      vitro models, the present study enquired if 2-(dimethylamino)-N-(5,6-dihydro-6
      oxophenanthridin-2yl)acetamide (PJ 34), a pharmacological inhibitor of PARP-1,
      could counteract the excitotoxic damage evoked by transient application (1 h) of
      kainate, a potent analogue of glutamate. Kainate induced dose-dependent (1 MUM
      threshold) neuronal loss (without damage to astrocytes) detected 24 h later via a
      PARP-1 dependent process that had peaked at 4 h after washout kainate. All spinal
      regions (ventral, central and dorsal) were affected, even though the largest
      damage was found in the dorsal area. Whereas PJ 34 did not protect against a
      large concentration (100 MUM) of kainate, it significantly inhibited neuronal
      losses evoked by 10 MUM kainate as long as it was co-applied with this glutamate
      agonist. When the application of PJ 34 was delayed to the washout time,
      neuroprotection was weak and regionally restricted. These data suggest that
      kainate-induced parthanatos developed early and was prevented by PJ 34 only when
      it was co-applied together with excitotoxic stimulus. Our results highlight the
      difficulty to arrest parthanatos as a mechanism of spinal neuron death in view of
      its low threshold of activation by kainate, its widespread distribution, and
      relatively fast development.

PMID- 21190077
TI  - BRCA1 and BRCA2 germline mutations in Uruguayan breast and breast-ovarian cancer
      families. Identification of novel mutations and unclassified variants.
AB  - The aim of the present study was to analyze BRCA1 and BRCA2 mutations in
      Uruguayan families with breast and breast/ovarian cancer. Probands from 42
      families with at least three cases of female breast cancer (BC) or two cases and
      subcriteria (paternal transmission, ovarian cancer, bilateral BC, male BC,
      Ashkenazi Jewish ancestry) in the same lineage, at least one diagnosed before age
      50, were screened for germline mutations. PCR amplification of all exons and
      intron-exon boundaries were performed, followed by protein truncation test,
      heteroduplex analysis, and direct sequencing. We identified seven different
      truncating mutations in seven families, five in BRCA2 (three in site-specific BC
      families and two in breast-ovarian cancer families) and two in BRCA1 (one in a
      site-specific BC family and the other in a breast-ovarian cancer family). Both
      BRCA1 mutations (5583insT and 2687T>G) and one of the five BRCA2 mutations
      (3829insTdel35) were not previously reported. We also detected ten sequence
      variants of unknown significance, five of them not described before. The low
      frequency of BRCA1/2 mutations (0.17) is in agreement with that reported in
      studies which included families with similar selection criteria. However, the
      observed predominance of BRCA2 (0.12) over BRCA1 mutations (0.05) is in contrast
      with the higher proportion of BRCA1 mutations communicated for most previous
      studies, even those with a predominance of site-specific BC families. Meanwhile,
      it has been described in one Chilean and some Spanish and Italian reports,
      highlighting the strong dependence between the mutational spectra and the
      ethnicity of the population analyzed.

PMID- 21190078
TI  - Classification of breast cancer precursors through exhaled breath.
AB  - Certain benign breast diseases are considered to be precursors of invasive breast
      cancer. Currently available techniques for diagnosing benign breast conditions
      lack accuracy. The purpose of this study was to deliver a proof-of-concept for a
      novel method that is based on breath testing to identify breast cancer
      precursors. Within this context, the authors explored the possibility of using
      exhaled alveolar breath to identify and distinguish between benign breast
      conditions, malignant lesions, and healthy states, using a small-scale, case
      controlled, cross-sectional clinical trial. Breath samples were collected from 36
      volunteers and were analyzed using a tailor-made nanoscale artificial NOSE (NA
      NOSE). The NA-NOSE signals were analyzed using two independent methods: (i)
      principal component analysis, ANOVA and Student's t-test and (ii) support vector
      machine analysis to detect statistically significant differences between the sub
      populations. The NA-NOSE could distinguish between all studied test populations.
      Breath testing with a NA-NOSE holds future potential as a cost-effective, fast,
      and reliable diagnostic test for breast cancer risk factors and precursors, with
      possible future potential as screening method.

PMID- 21190079
TI  - Comparison of different approaches for assessment of HER2 expression on protein
      and mRNA level: prediction of chemotherapy response in the neoadjuvant GeparTrio
      trial (NCT00544765).
AB  - Human epidermal growth factor receptor 2 (HER2) testing is an essential part of
      pathological assessment in breast cancer patients, as HER2 provides not only
      prognostic but also predictive information on response to targeted therapy. So
      far, HER2 test accuracy of immunohistochemistry/in situ-hybridization techniques
      is still under debate, and more reliable and robust technologies are needed. To
      address this issue and to evaluate the predictive value of HER2 on chemotherapy,
      we investigated a cohort of 278 patients from the GeparTrio trial, a prospective
      neoadjuvant anthracycline/taxane-based multicenter study. In the GeparTrio trial,
      patients were not treated with any anti-HER2 therapy, as this was not standard
      therapy at this time. The HER2 status was analyzed by three different approaches:
      local and central evaluation using immunohistochemistry combined with in situ
      hybridization as well as evaluation of HER2 mRNA expression using kinetic RT-PCR
      from formalin-fixed, paraffin-embedded (FFPE) tissue samples using a predefined
      cutoff. HER2 overexpression/amplification was observed in 37.3% (91/244) and
      17.9% (41/229) of the informative samples in the local and central evaluations,
      respectively. Positive HER2 mRNA levels were found in 19.8% (55/278). We observed
      a highly significant correlation between central HER2 expression and HER2 status
      measured by kinetic RT-PCR (r = 0.856, P < 0.0001) and an overall agreement of
      95.6% (kappa statistic, 0.862, CI 0.77-0.94). Further, central HER2 as well as
      HER2 mRNA expression were predictors for a pathological complete response after
      neoadjuvant anthracycline/taxane-based primary chemotherapy in a univariate
      binary logistic regression analysis (OR 3.29, P = 0.002; OR 2.65, P = 0.004). The
      predictive value could be confirmed for the central HER2 status by multivariate
      analysis (OR 3.04, P = 0.027). The locally assessed HER2 status was not
      predictive of response to chemotherapy. Our results suggest that standardized
      methods are preferable for evaluation of HER2 status. The kinetic RT-PCR from
      FFPE tissue might be an additional approach for assessment of this important
      prognostic and predictive parameter but has to be confirmed by other studies.

PMID- 21190080
TI  - Spatial and temporal dynamic of trophic relevant parameters in a subtropical
      coastal lagoon in Brazil.
AB  - Coastal lagoons are ecologically and economically important environments but a
      relative low number of studies were carried out in subtropical and permanently
      closed coastal lagoons. The present study aimed at assessing the temporal and
      spatial dynamic of trophic relevant water quality parameters in the small, deep
      and freshwater Peri coastal lagoon, South Brazil. During the 19 sampled months
      (March/2008-September/2009) spatial homogeneity (horizontal and vertical) was
      registered in all seasons for all variables, a condition related to the strong
      wind influence and low human occupation in the lagoon watershed. Seasonal
      variations of the water quality could be observed and they can be explained
      mainly by variation on temperature, wind forces and direction and rainfall,
      characteristic from the subtropical weather. Comparing this study with two others
      conducted in Peri lagoon in 1996 and 1998, no critical differences that evidence
      alteration in the water quality were found, but climate differences may have
      influenced in some small variations observed. The use of four trophic state
      indices indicated that indices designed for temperate lakes are inappropriate for
      the subtropical Peri lagoon. The lagoon was classified as oligotrophic for
      nutrients concentrations and meso-eutrophic for transparency and chlorophyll-a,
      which can be explained by the high densities and monodominance of the
      cyanobacterium Cylindrospermopsis raciborskii and the high recycling rates
      observed in warmer water bodies, when compared to the temperate ones.

PMID- 21190081
TI  - Renal creatinine handling in very old patients with chronic renal disease.
AB  - Renal creatinine handling is basically the result of its glomerular filtration
      and proximal tubular secretion. However, creatinine reabsorption has been
      documented in certain conditions, such as premature babies, newborns, and healthy
      elderly people. Additionally, it is known that there is an increase in the
      proportion of secreted creatinine in chronic renal disease. In this paper, we
      report our studies on the characteristic reabsorption pattern of creatinine in
      the elderly with chronic renal disease. MATERIAL & METHOD: We studied twenty
      seven volunteers with chronic kidney disease, eleven of whom were young and the
      rest were very old (age > 75 years old). We measured creatinine clearance without
      (Ccr) and with cimetidine (CcrWC) and Ccr/CcrWC ratio from each volunteer, in
      timed urine samples. Then, Ccr, CcrWC, and Ccr/CcrWC ratio were compared between
      young and very old people in two chronic kidney disease subgroups: stages II-III
      and stages IV-V. Statistical analysis was performed applying a non-parametric
      test (Wilcoxon). RESULTS: We observed a tendency towards a lower Ccr/CcrWC ratio
      in the very old stage II-III group compared with the young one: 1 (0.96-1.26)
      (very old) vs 1.3 (1.1-1.5) (young), P = 0.09, on the contrary, there was no
      significant difference in Ccr/CcrWC ratio between very old and young person with
      stage IV-V CKD: 1.66 (1.41-2.21) (young) vs 1.77 (1.1-2.7) (young), P = NS.
      CONCLUSION: Creatinine secretion pattern in very old patients with advanced
      chronic renal disease is similar to that observed in young ones with similar
      level of CKD.

PMID- 21190082
TI  - Percutaneous nephrolithotomy for staghorn kidney stones in elderly patients.
AB  - PURPOSE: We retrospectively analyzed the results of percutaneous nephrolithotomy
      operations for treatment of staghorn kidney stone disease in elderly patients and
      compared surgical parameters and outcomes with a control group of young adult
      patients. PATIENTS AND METHOD: Between 2002 and 2010, 300 consecutive patients
      underwent percutaneous nephrolithotomy operation for treatment of staghorn kidney
      stone disease. Forty-five of the patients were older than 65 years and considered
      to be in elderly group. Thirty-seven of the patients were between the ages 18 and
      36 years and considered to be the control group. Surgical parameters and outcomes
      were compared between groups. RESULTS: There were no significant differences
      between groups for stone area, operation time, difference in hemoglobin levels
      before and after surgery, blood transfusion rate, and length of hospital (P =
      0.230, P = 0.106, P = 0.395, P = 0.691, and P = 0.690, respectively). Success
      rates after the operations were 53% in elderly group and 38% in young adult
      group. The difference for the outcomes of the operations was statistically
      insignificant (P = 0.365). Thirty-three (73%) of the patients had associated
      comorbid diseases in elderly group, while no patients had any comorbid disease in
      control group. Statistical analyses revealed no significant relation between the
      presence of comorbid diseases or ipsilateral renal surgery with success rate of
      the operation in the elderly group (P = 0.26 and P = 0.222, respectively).
      CONCLUSIONS: The management of kidney stone disease by percutaneous
      nephrolithotomy in elderly patients is an adequate treatment modality even in the
      presence of complete staghorn calculi, comorbid diseases or previous ipsilateral
      renal surgery.

PMID- 21190083
TI  - Factors affecting accumulation and degradation of curdlan, trehalose and glycogen
      in cultures of Cellulomonas flavigena strain KU (ATCC 53703).
AB  - Cellulomonas flavigena strain KU (ATCC 53703) is a cellulolytic, Gram-positive
      bacterium which produces large quantities of an insoluble exopolysaccharide (EPS)
      when grown in minimal media with a high carbon-to-nitrogen (C/N) ratio. Earlier
      studies proved the EPS is structurally identical to the linear beta-1,3-glucan
      known as curdlan and provided evidence that the EPS functions as a carbon and
      energy reserve compound. We now report that C. flavigena KU also accumulates two
      intracellular, glucose-storage carbohydrates under conditions of carbon and
      energy excess. These carbohydrates were partially purified and identified as the
      disaccharide trehalose and a glycogen/amylopectin-type polysaccharide. A novel
      method is described for the sequential fractionation and quantitative
      determination of all three carbohydrates from culture samples. This fractionation
      protocol was used to examine the effects of C/N ratio and osmolarity on the
      accumulation of cellular carbohydrates in batch culture. Increasing the C/N of
      the growth medium caused a significant accumulation of curdlan and glycogen but
      had a relatively minor effect on accumulation of trehalose. In contrast,
      trehalose levels increased in response to increasing osmolarity, while curdlan
      levels declined and glycogen levels were generally unaffected. During starvation
      for an exogenous source of carbon and energy, only curdlan and glycogen showed
      substantial degradation within the first 24 h. These results support the
      conclusion that extracellular curdlan and intracellular glycogen can both serve
      as short-term reserve compounds for C. flavigena KU and that trehalose appears to
      accumulate as a compatible solute in response to osmotic stress.

PMID- 21190084
TI  - 1st international pichia anomala mini-symposium.

PMID- 21190085
TI  - Panaxydol induces apoptosis through an increased intracellular calcium level,
      activation of JNK and p38 MAPK and NADPH oxidase-dependent generation of reactive
      oxygen species.
AB  - Panaxydol, a polyacetylenic compound derived from Panax ginseng roots, has been
      shown to inhibit the growth of cancer cells. In this study, we demonstrated that
      panaxydol induced apoptosis preferentially in transformed cells with a minimal
      effect on non-transformed cells. Furthermore, panaxydol was shown to induce
      apoptosis through an increase in intracellular Ca(2+) concentration
      ([Ca(2+)](i)), activation of JNK and p38 MAPK, and generation of reactive oxygen
      species (ROS) initially by NADPH oxidase and then by mitochondria. Panaxydol
      induced apoptosis was caspase-dependent and occurred through a mitochondrial
      pathway. ROS generation by NADPH oxidase was critical for panaxydol-induced
      apoptosis. Mitochondrial ROS production was also required, however, it appeared
      to be secondary to the ROS generation by NADPH oxidase. Activation of NADPH
      oxidase was demonstrated by the membrane translocation of regulatory p47(phox)
      and p67(phox) subunits and shown to be necessary for ROS generation by panaxydol
      treatment. Panaxydol triggered a rapid and sustained increase of [Ca(2+)](i),
      which resulted in activation of JNK and p38 MAPK. JNK and p38 MAPK play a key
      role in activation of NADPH oxidase, since inhibition of their expression or
      activity abrogated membrane translocation of p47(phox) and p67(phox) subunits and
      ROS generation. In summary, these data indicate that panaxydol induces apoptosis
      preferentially in cancer cells, and the signaling mechanisms involve a
      [Ca(2+)](i) increase, JNK and p38 MAPK activation, and ROS generation through
      NADPH oxidase and mitochondria.

PMID- 21190086
TI  - M3: Microscope-based maskless micropatterning with dry film photoresist.
AB  - We present a maskless micropatterning system that utilizes a fluorescence
      microscope with programmable X-Y stage and dry film photoresist to realize
      feature sizes in the sub-millimeter range (40-700 MUm). The method allows for
      flexible in-house maskless photolithography without a dedicated microfabrication
      facility and is well-suited for rapid prototyping of microfluidic channels,
      scaffold templates for protein/cell patterning or optically-guided cell
      encapsulation for biomedical applications.

PMID- 21190087
TI  - Causation and melanoma classification.
AB  - In this article, I begin by giving a brief history of melanoma causation. I then
      discuss the current manner in which malignant melanoma is classified. In general,
      these systems of classification do not take account of the manner of tumour
      causation. Instead, they are based on phenomenological features of the tumour,
      such as size, spread, and morphology. I go on to suggest that misclassification
      of melanoma is a major problem in clinical practice. I therefore outline an
      alternative means of classifying these tumours based on causal factors. By
      analogy with similar systems that have recently emerged for other cancers, I
      suggest that this causal classification is likely to be both workable and
      helpful, even in the absence of a full causal-mechanistic understanding of the
      aetiology of the tumour.

PMID- 21190088
TI  - Complex sleep apnea unmasked by the use of a mandibular advancement device.
AB  - According to most accepted definitions, complex sleep apnea syndrome (CompSAS) is
      described as an emergence of central apneas in a patient with obstructive sleep
      apnea (OSA) upon introduction of continuous positive airway pressure therapy
      (CPAP). We present two patients who developed comparable central apnea activity
      when treated with either a CPAP device or a mandibular advancement device. As
      similar findings have been previously documented in patients with OSA treated
      with maxillofacial surgery or tracheostomy, we propose that the current
      definition of CompSAS should broaden to include diagnosis of CompSAS in non-PAP
      treated patients, who are managed with either a dental appliance or a surgical
      procedure.

PMID- 21190089
TI  - Fetomaternal transfusion after amniocentesis and cordocentesis.
AB  - OBJECTIVE: To compare the extent of fetomaternal transfusion after amniocentesis
      and cordocentesis. SETTING: Three-hundred and forty-five amniocentesis and 268
      cordocentesis were performed for genetic indications. The extent of fetomaternal
      transfusion was calculated on the basis of the maternal serum alpha-fetoprotein
      level changes. RESULTS: The mean fetomaternal transfusion was 6.3 and 62 MUL in
      the amniocentesis and cordocentesis groups, respectively. Transplacental needle
      passage and longer procedural time were risk factors for fetomaternal
      transfusion. The frequency of transplacental passage was higher and the
      procedural time was longer in the cordocentesis group. The fetal loss rate was
      1.17% after amniocentesis and 1.2% after cordocentesis, respectively.
      CONCLUSIONS: Cordocentesis causes more injury to the extrafetal compartment,
      which results in a higher level of fetomaternal transfusion. However, though a
      nearly ten times higher fetomaternal transfusion was observed after
      cordocentesis, there was no essential difference in pregnancy outcome between the
      two groups.

PMID- 21190090
TI  - Effects of pulsed electric field on secondary metabolism of Vitis vinifera L. cv.
      Gamay Freaux suspension culture and exudates.
AB  - Plant cell cultures provide a large potential for the production of secondary
      metabolites. Through the application of different physical and chemical cell
      stress factors, we investigated the production of the secondary metabolites in
      plant cell cultures. The effects of pulsed electric field (PEF) and ethephon on
      growth and secondary metabolism, particularly anthocyanins and phenolic acids
      synthesis, were investigated by using suspension culture of Vitis vinifera L. cv.
      Gamay Freaux as a model system. Anthocyanins were measured by spectrophotometer
      and extracellular phenolic acids were determined by high-performance liquid
      chromatography. The compounds were identified by liquid chromatography-mass
      spectrometry and nuclear magnetic resonance. After the treatments with PEF and
      ethephon, the concentrations of anthocyanins and phenolic acids in cell culture
      were higher than in the control, without loss of biomass. The combination of PEF
      treatment and ethephon improved secondary metabolites formation. Production
      levels of extracellular phenolic acids, 3-O-glucosyl-resveratrol were increased
      by PEF and ethephon treatments. The results show that PEF induced a defense
      response of plant cells and may have altered the cell/membrane's dielectric
      properties. PEF, an external stimulus or stress, is proposed as a promising new
      abiotic elicitor for stimulating secondary metabolites biosynthesis in plant cell
      cultures.

PMID- 21190091
TI  - Inflammatory profile, age of onset, and the MTHFR polymorphism in patients with
      multiple sclerosis.
AB  - Both genetic and inflammatory factors are suspected in the etiology of multiple
      sclerosis (MS). Of genetic factors, the methylenetetrahydrofolate reductase
      (MTHFR) C677T polymorphism has been associated with increased levels of plasma
      homocysteine, a neuronal excitotoxic amino acid. Sclerotic patients also have
      elevated levels of plasma and CSF homocysteine. In this study, the association
      between C677T polymorphism and MS was tested by recruiting 230 healthy and 194
      multiple sclerotic age- and gender-matched patients. The MTHFR C677T polymorphism
      and the serum levels of inflammatory mediators IL-1beta, TNFalpha, and CRP were
      measured. TNFalpha, CRP, and IL-1beta levels were significantly higher in
      sclerotic patients. T allele was 1.7 times more present in this group. In
      patient's group, the levels of all inflammatory mediators were higher in T/T
      compared to two other genotypes. Evaluation of the age of onset of disease
      revealed that subjects with T allele developed the MS disease, almost 4 years
      sooner than other genotype. We concluded that having T allele of C677T in MS
      might be accompanied with higher levels of serum inflammatory mediators and a
      vulnerability to earlier age of onset of disease. Further studies are needed to
      elucidate the underlying mechanisms.

PMID- 21190092
TI  - Resectable pancreatic metastasis of left thighbone leiomyosarcoma: case report
      and literature review.
AB  - INTRODUCTION: Metastases to the pancreas gland are uncommon, especially from
      leiomyosarcoma. We report a case of asymptomatic pancreatic metastasis resection
      of leiomyosarcoma. CASE REPORT: A 59-year-old patient was treated for thighbone
      leiomyosarcoma, with surgical resection and adjuvant radiotherapy. After 4 years
      of follow-up, although that patient was asymptomatic, a pancreatic metastasis was
      identified by CT and fine needle aspiration. Open left pancreatectomy was
      performed. DISCUSSION: We discuss diagnosis findings and interest in the surgical
      resection. Furthermore, we reviewed previously reported cases.

PMID- 21190093
TI  - Hepatocellular carcinoma presenting as an incidental isolated malignant portal
      vein thrombosis.
AB  - INTRODUCTION: Portal vein thrombosis is frequently associated with hepatocellular
      carcinoma (HCC). Tumor invasion into the portal vein by direct venous extension
      or metastasis occurs in up to 70% of HCC patients (Cedrone et al., Liver 16:94-8,
      1996). However, presentation as an isolated malignant portal vein thrombosis
      without any evidence of obvious hepatoma-like lesions in the liver by imaging
      studies is extremely uncommon. We present an unusual case of HCC presenting as a
      malignant portal vein thrombus, proven on biopsy of the thrombus without any
      evidence of primary liver lesion. This, to our knowledge, is the first case of
      HCC presenting as an incidental isolated malignant portal vein thrombosis. The
      importance of doing delayed enhancement imaging studies to rule out malignant
      portal vein thrombosis is emphasized. CASE REPORT: A 60-year-old man presented
      with acute substernal chest pain. Physical examination revealed icterus.
      Examination of the abdomen did not reveal any organomegaly. Liver function test
      revealed a predominantly conjugated bilirubinemia. Abdominal sonogram revealed
      thrombosis and occlusion of the posterior right portal vein. Liver parenchyma was
      homogenous with no intrahepatic mass. Computed tomography (CT) of the abdomen and
      pelvis after administration of oral and intravenous contrast with delayed views
      revealed arterial enhancement of the right portal vein thrombus with delayed
      washout. MRI of the abdomen with gadolinium confirmed the right portal vein
      thrombus without focal hepatic mass. Aspiration of the right portal vein thrombus
      under CT guidance revealed hepatocellular carcinoma which was confirmed by
      immunohistochemistry. Serum alpha-fetoprotein level was very high. Patient was
      started on sorafenib with subsequent decrease in alpha-fetoprotein level. He was
      doing well till the date of this report. DISCUSSION: This unusual case of
      hepatocellular carcinoma presenting as an incidental malignant portal vein
      thrombosis without any primary liver lesion is extremely rare. Other reported
      cases of malignant portal vein thrombosis have been in patients with underlying
      hepatoma, cirrhosis, or with intrabiliary hepatocelluar carcinoma. In the
      clinical setting of portal vein thrombosis, imaging studies showing enhancement
      of the thrombus in the arterial phase are important in leading to the diagnosis
      of malignancy.

PMID- 21190094
TI  - Pro-apoptotic and anti-proliferative effects of mitofusin-2 via Bax signaling in
      hepatocellular carcinoma cells.
AB  - Mitochondrial GTPase mitofusin-2 (Mfn2) is a novel gene that remarkably
      suppresses the injury-mediated proliferation of vascular smooth muscle cells
      (VSMCs) and has a potential apoptotic effect via the mitochondrial apoptotic
      pathway. Hepatocellular carcinoma (HCC) tissues and matched normal tissues were
      examined for mfn2 expression. HCC cells were infected with adenovirus carrying
      Mfn2 (Ad-mfn2) or green fluorescent protein (Ad-GFP), used as a control. Short
      hairpin RNA (shRNA) was formed by shR-mfn2 and shR-Bax to repress mfn2 and Bax
      transcription, respectively. The effects of mfn2 on cell cycle distribution and
      apoptosis were measured by flow cytometric analysis. Significant downregulation
      of mfn2 was observed in HCC tissues compared with nearby normal tissues.
      Overexpression of mfn2 inhibited HCC cell proliferation and induced apoptosis by
      increasing the level of active caspase-3 and poly (ADP-ribose) polymerase (PARP)
      cleavage. Overexpression of mfn2 also induced cytochrome c release to the
      cytoplasm by enhancing Bax translocation from the cytoplasm to the mitochondrial
      membrane. Upregulation of mfn2 promoted apoptosis of HCC cells, and this was
      dramatically suppressed by shR-Bax. Our results show that the mfn2 gene is a
      potential tumor suppressor target that may significantly promote apoptosis via
      Bax and may inhibit proliferation in HCC cells. This gene may be an important
      therapeutic target for the treatment of tumors or hyperproliferative diseases.

PMID- 21190095
TI  - Metabolic imaging for identifying antecedent myocardial ischemia and acute
      coronary syndrome in the emergency department.

PMID- 21190096
TI  - MTHFR 677C>T effects on anterior cingulate structure and function during response
      monitoring in schizophrenia: a preliminary study.
AB  - Patients with schizophrenia exhibit deficient response monitoring as indexed by
      blunted activation of the dorsal anterior cingulate cortex (dACC) and
      functionally related regions during error commission. This pattern may reflect
      heritable alterations of dACC function. We examined whether the hypofunctional
      677C>T variant in MTHFR, a candidate schizophrenia risk gene, contributed to our
      previous findings of blunted error-related dACC activation and reduced
      microstructural integrity of dACC white matter. Eighteen medicated outpatients
      with schizophrenia underwent diffusion tensor imaging and performed an
      antisaccade paradigm during functional magnetic resonance imaging (fMRI). T
      allele carriers exhibited significantly less error-related activation than C/C
      patients in bilateral dACC and substantia nigra, regions that are thought to
      mediate dopamine-dependent error-based reinforcement learning. T carrier patients
      also showed significantly lower fractional anisotropy in bilateral dACC. These
      findings suggest that the MTHFR 677T allele blunts response monitoring in
      schizophrenia, presumably via effects on dopamine signaling and dACC white matter
      microstructural integrity.

PMID- 21190097
TI  - Managing malignant cerebral infarction.
AB  - OPINION STATEMENT: Managing patients with malignant cerebral infarction remains
      one of the foremost challenges in medicine. These patients are at high risk for
      progressive neurologic deterioration and death due to malignant cerebral edema,
      and they are best cared for in the intensive care unit of a comprehensive stroke
      center. Careful initial assessment of neurologic function and of findings on MRI,
      coupled with frequent reassessment of clinical and radiologic findings using CT
      or MRI are mandatory to promote the prompt initiation of treatments that will
      ensure the best outcome in these patients. Significant deterioration in either
      neurologic function or radiologic findings or both demand timely treatment using
      the best medical management, which may include osmotherapy (mannitol or
      hypertonic saline), endotracheal intubation, and mechanical ventilation. Under
      appropriate circumstances, decompressive craniectomy may be warranted to improve
      outcome or to prevent death.

PMID- 21190098
TI  - Operative management of nonunion scaphoid fracture in children: a case report and
      literature review.
AB  - Scaphoid fractures are uncommon in children, but if maltreated, they can result
      in nonunion. The authors report a case of left scaphoid nonunion in an 11-year
      old boy. The operative management of this pseudarthrosis was performed (K-wire
      fixation and bone grafting of scaphoid). After a 10-month follow-up period, the
      left wrist regained a full range of motion with no impairment. The roentgenograms
      showed union of the scaphoid. Surgical management of scaphoid nonunion fractures
      in children offers successful fusion, with very low nonunion rate and patient's
      satisfaction.

PMID- 21190099
TI  - Three-dimensional analysis of image-free navigation system for total knee
      arthroplasty.
AB  - Malalignment causes abnormal forces that may lead to loosening after knee
      replacement. Whether a computer-assisted technique can improve the precision of
      implant positioning guaranteeing good long-term results in total knee
      arthroplasty, this is a matter of discussion. The authors evaluate the alignment
      accuracy of 20 primary total knee arthroplasties, performed using an image-free
      computer navigation systems, with standardized CT protocol and three-dimensional
      digital model reconstruction. The results of this study demonstrate that the
      image-free navigation system is able to improve accuracy in axial limb alignment
      and positioning of the components in the majority of cases; moreover, the
      difference between the mean mechanical axis value of the navigation system (179.7
      degrees  +/- 1.7 degrees ) and the median mean value obtained during the post
      operative evaluation (180.3 degrees  +/- 1.9 degrees ) is not statistically
      significant (P = 0.28).

PMID- 21190100
TI  - The potential role for the use of cardiac computed tomography angiography for the
      acute chest pain patient in the emergency department.

PMID- 21190101
TI  - Prognostic relevance of pathologic subtypes and minimal invasion in intraductal
      papillary mucinous neoplasms of the pancreas.
AB  - Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are classified
      into the following four histopathologic subtypes: gastric, intestinal,
      pancreatobiliary, and oncocytic. However, the clinicopathologic characteristics
      of IPMN subtypes have not been fully clarified. Recently, a subgroup
      classification of minimally invasive intraductal papillary mucinous carcinomas
      (MI-IPMCs) was suggested in contrast to overt invasive carcinoma from IPMCs (IC
      IPMCs). The purpose of this study was to determine whether or not the pathologic
      subtype classification can predict prognosis and to validate the usefulness of
      the newly proposed diagnostic criteria of MI-IPMCs. We reviewed the
      clinicopathologic characteristics of 142 surgically resected cases of IPMNs.
      There were 54, 56, 30, and two cases of the gastric, intestinal,
      pancreatobiliary, and oncocytic types of IPMNs, respectively. The intestinal and
      pancreatobiliary types were more likely to have a main duct type. All gastric
      type tumors were adenomas or moderate dysplasia, whereas greater than one half of
      the intestinal and pancreatobiliary types were carcinomas in situ or invasive
      carcinomas. A significant difference in recurrence and death rate was noted for
      invasive carcinoma between the intestinal and pancreatobiliary types. The
      majority of MI-IPMCs were the intestinal type, whereas the majority of IC-IPMCs
      were the pancreatobiliary type. The IC-IPMC group showed a decreased recurrence
      free and overall survival with statistically significance (p < 0.001 and p =
      0.001, respectively). Our results suggest that the pathologic subtype
      classification and the newly proposed diagnostic criteria for minimal invasion
      may also be useful to predict prognosis of IPMNs of the pancreas.

PMID- 21190102
TI  - Investigation of element distribution and homogeneity of TXRF samples using SR
      micro-XRF to validate the use of an internal standard and improve external
      standard quantification.
AB  - Total reflection X-ray fluorescence analysis (TXRF) offers a nondestructive
      qualitative and quantitative analysis of trace elements. Due to its outstanding
      properties TXRF is widely used in the semiconductor industry for the analysis of
      silicon wafer surfaces and in the chemical analysis of liquid samples. Two
      problems occur in quantification: the large statistical uncertainty in wafer
      surface analysis and the validity of using an internal standard in chemical
      analysis. In general TXRF is known to allow for linear calibration. For small
      sample amounts (low nanogram (ng) region) the thin film approximation is valid
      neglecting absorption effects of the exciting and the detected radiation. For
      higher total amounts of samples deviations from the linear relation between
      fluorescence intensity and sample amount can be observed. This could be caused by
      the sample itself because inhomogeneities and different sample shapes can lead to
      differences of the emitted fluorescence intensities and high statistical errors.
      The aim of the study was to investigate the elemental distribution inside a
      sample. Single and multi-element samples were investigated with Synchrotron
      radiation-induced micro X-ray Fluorescence Analysis (SR-MU-XRF) and with an
      optical microscope. It could be proven that the microscope images are all based
      on the investigated elements. This allows the determination of the sample shape
      and potential inhomogeneities using only light microscope images. For the multi
      element samples, it was furthermore shown that the elemental distribution inside
      the samples is homogeneous. This justifies internal standard quantification.

PMID- 21190103
TI  - Porous polymer monoliths for small molecule separations: advancements and
      limitations.
AB  - Porous polymer monoliths are considered to be one of the major breakthroughs in
      separation science. These materials are well known to be best suited for the
      separation of large molecules, specifically proteins, an observation most often
      explained by convective mass transfer and the absence of small pores in the
      polymer scaffold. However, this conception is not sufficient to explain the
      performance of small molecules. This review focuses in particular on the
      preparation of (macro)porous polymer monoliths by simple free-radical processes
      and the key events in their formation. There is special focus on the fluid
      transport properties in the heterogeneous macropore space (flow dispersion) and
      on the transport of small molecules in the swollen, and sometimes permanently
      porous, globule-scale polymer matrix. For small molecule applications in liquid
      chromatography, it is consistently found in the literature that the major limit
      for the application of macroporous polymer monoliths lies not in the optimization
      of surface area and/or modification of the material and microscopic morphological
      properties only, but in the improvement of mass transfer properties. In this
      review we discuss the effect of resistance to mass transfer arising from the
      nanoscale gel porosity. Gel porosity induces stagnant mass transfer zones in
      chromatographic processes, which hamper mass transfer efficiency and have a
      detrimental effect on macroscopic chromatographic dispersion under equilibrium
      (isocratic) elution conditions. The inherent inhomogeneity of polymer networks
      derived from free-radical cross-linking polymerization, and hence the absence of
      a rigid (meso)porous pore space, represents a major challenge for the preparation
      of efficient polymeric materials for the separation of small molecules.

PMID- 21190104
TI  - Strategies to extend the lifetime of bioelectrochemical enzyme electrodes for
      biosensing and biofuel cell applications.
AB  - Enzymes are powerful catalysts for biosensor and biofuel cell electrodes due to
      their unique substrate specificity. This specificity is defined by the amino acid
      chain's complex three-dimensional structure based on non-covalent forces, being
      also responsible for the very limited enzyme lifetime of days to weeks. Many
      electrochemical applications, however, would benefit from lifetimes over months
      to years. This mini-review provides a critical overview of strategies and ideas
      dealing with the problem of short enzyme lifetime, which limits the overall
      lifetime of bioelectrochemical electrodes. The most common approaches aim to
      stabilize the enzyme itself. Various immobilization techniques have been used to
      reduce flexibility of the amino acid chain by introducing covalent or non
      covalent binding forces to external molecules. The enzyme can also be stabilized
      using genetic engineering methods to increase the binding forces within the
      protein or by optimizing the environment in order to reduce destabilizing
      interactions. In contrast, renewing the inactivated catalyst decouples overall
      system lifetime from the limited enzyme lifetime and thereby promises
      theoretically unlimited electrode lifetimes. Active catalyst can be supplied by
      exchanging the electrolyte repeatedly. Alternatively, integrated microorganisms
      can display the enzymes on their surface or secrete them to the electrolyte,
      allowing unattended power supply for long-term applications.

PMID- 21190105
TI  - Current findings, future trends, and unsolved problems in studies of medicinal
      mushrooms.
AB  - The target of the present review is to draw attention to many critically
      important unsolved problems in the future development of medicinal mushroom
      science in the twenty-first century. Special attention is paid to mushroom
      polysaccharides. Many, if not all, higher Basidiomycetes mushrooms contain
      biologically active polysaccharides in fruit bodies, cultured mycelium, and
      cultured broth. The data on mushroom polysaccharides are summarized for
      approximately 700 species of higher Hetero- and Homobasidiomycetes. The chemical
      structure of polysaccharides and its connection to antitumor activity, including
      possible ways of chemical modification, experimental testing and clinical use of
      antitumor or immunostimulating polysaccharides, and possible mechanisms of their
      biological action, are discussed. Numerous bioactive polysaccharides or
      polysaccharide-protein complexes from medicinal mushrooms are described that
      appear to enhance innate and cell-mediated immune responses and exhibit antitumor
      activities in animals and humans. Stimulation of host immune defense systems by
      bioactive polymers from medicinal mushrooms has significant effects on the
      maturation, differentiation, and proliferation of many kinds of immune cells in
      the host. Many of these mushroom polymers were reported previously to have
      immunotherapeutic properties by facilitating growth inhibition and destruction of
      tumor cells. While the mechanism of their antitumor actions is still not
      completely understood, stimulation and modulation of key host immune responses by
      these mushroom polymers appears central. Particularly and most importantly for
      modern medicine are polysaccharides with antitumor and immunostimulating
      properties. Several of the mushroom polysaccharide compounds have proceeded
      through phases I, II, and III clinical trials and are used extensively and
      successfully in Asia to treat various cancers and other diseases. A total of 126
      medicinal functions are thought to be produced by medicinal mushrooms and fungi
      including antitumor, immunomodulating, antioxidant, radical scavenging,
      cardiovascular, antihypercholesterolemia, antiviral, antibacterial,
      antiparasitic, antifungal, detoxification, hepatoprotective, and antidiabetic
      effects.

PMID- 21190106
TI  - Discovery and characterization of D-phenylserine deaminase from Arthrobacter sp.
      TKS1.
AB  - We discovered a D-phenylserine deaminase that catalyzed the pyridoxal 5'
      phosphate (PLP)-dependent deamination reaction from D-threo-phenylserine to
      phenylpyruvate in newly isolated Arthrobacter sp. TKS1. The enzyme was partially
      purified, and its N-terminal amino acid sequence was analyzed. Based on the
      sequence information, the gene encoding the enzyme was identified and expressed
      in Escherichia coli. The expressed protein was purified to homogeneity and
      characterized. The enzyme consisted of two identical 46-kDa subunits and showed
      maximum activity at pH 8.5 and 55 degrees C. The enzyme was stable in the range
      of pH 7.5 to pH 8.5 and up to 50 degrees C. The enzyme acted on the D-forms of
      beta-hydroxy-alpha-amino acids, such as D-threo-phenylserine (K(m), 19 mM), D
      serine (K(m), 5.8 mM), and D-threonine (K(m), 102 mM). As L-threonine, D-allo
      threonine, L-allo-threonine, and DL-erythro-phenylserine were inert, the enzyme
      could distinguish D-threo-form from among the four stereoisomers of phenylserine
      or threonine. The enzyme was activated by ZnSO(4), CuSO(4), BaCl(2), and CoCl(2)
      and strongly inhibited by phenylhydrazine, sodium borohydride, hydroxylamine, and
      DL-penicillamine. The enzyme exhibited absorption maxima at 280 and around 415
      nm. The enzyme has an N-terminal domain similar to that of alanine racemase,
      which belongs to the fold type III group of pyridoxal enzymes.

PMID- 21190107
TI  - Mutational analysis of wheat (Triticum aestivum L.) nucleotide
      pyrophosphatase/phosphodiesterase shows the role of six amino acids in the
      catalytic mechanism.
AB  - Nucleotide pyrophosphatases/phosphodiesterases (NPPs, PF01663) release nucleoside
      5'-monophosphates from a wide range of nucleotide substrates. Only very recently,
      the first plant members of the NPP family were characterised (Joye et al. J
      Cereal Sci 51: 326-336, 2010), and little is known about their substrate
      specifying residues. We elucidated the role of six amino acid residues of the
      recently identified and characterised Triticum aestivum L. NPP (Joye et al. J
      Cereal Sci 51: 326-336, 2010). Substitution of the highly conserved catalytic
      Thr132 into Ser or Ala completely abolished enzyme activity. Mutation of a highly
      conserved His255 residue into an apolar Ala suprisingly increased enzyme activity
      against most phosphodiester substrates. Four other residues moderately to highly
      conserved over NPPs of different organisms were studied as well. Mutation of the
      Asn153, Asn165 and Glu199 into an Arg, Ser and Asp residue, respectively,
      increased the relative enzyme activity against p-nitrophenyl phosphate.
      Furthermore, mutation of Phe194 into Ser increased the relative enzyme activity
      against adenosine 5'-monophosphate-containing substrates, although the overall
      enzyme activity of this mutant enzyme decreased. We conclude that the structural
      requirements and the conservation of the amino acids of the catalytic site of
      TaNPPr and, by extension, probably of all NPPs, are very stringent.

PMID- 21190108
TI  - Robot-assisted versus laparoscopic Roux-en-Y gastric bypass: is there a
      difference in outcomes?
AB  - BACKGROUND: Application of the robot for Roux-en-Y gastric bypass has been slow
      to evolve, despite its rapid acceptance in other fields. This is largely due to
      associated costs of technology, reports of increased operative time, and
      inadequate data available to correlate the benefits of robotics to a clinical
      outcome. The authors present a comparative study between laparoscopic and robot
      assisted Roux-en-Y gastric bypass performed at a specialized institution for
      robotic surgery. MATERIALS AND METHOD: A total of 135 consecutive Roux-en-Y
      gastric bypass procedures were performed from January 2006 to December 2009 by a
      single surgeon. The first 45 were performed laparoscopically and the remaining 90
      were robot-assisted. Patient demographics, operative time, complication rate,
      length of stay, long-term weight loss, and follow-up for the two groups were
      gathered from a prospectively maintained database and statistically analyzed.
      RESULTS: The overall operative time was significantly shorter for the robot
      assisted procedures than for the laparoscopic procedures (207 +/- 31 vs. 227 +/-
      31 min) (P = 0.0006). The robotic set-up time remained constant at 13 +/- 4 min.
      30 robotic cases were necessary in order to perform the procedure in less time
      than with the laparoscopic approach (P = 0.047). Mortality was 0% in both groups,
      with no conversions to open surgery and no transfusions. Early morbidities and
      percentage of excess weight loss at 1 year were comparable for the two groups.
      CONCLUSIONS: The use of the robot for performing the gastrojejunostomy during
      laparoscopic Roux-en-Y gastric bypass does not increase the operative time or the
      rate of specific complications. The short-term outcomes of the robot-assisted
      procedure are comparable to those found with the conventional laparoscopic
      method.

PMID- 21190109
TI  - Do soft skills predict surgical performance?: a single-center randomized
      controlled trial evaluating predictors of skill acquisition in virtual reality
      laparoscopy.
AB  - BACKGROUND: Virtual reality (VR) training in minimal invasive surgery (MIS) is
      feasible in surgical residency and beneficial for the performance of MIS by
      surgical trainees. Research on stress-coping of surgical trainees indicates the
      additional impact of soft skills on VR performance in the surgical curriculum.
      The aim of this study was to evaluate the impact of structured VR training and
      soft skills on VR performance of trainees. METHOD: The study was designed as a
      single-center randomized controlled trial. Fifty first-year surgical residents
      with limited experience in MIS ("camera navigation" in laparoscopic
      cholecystectomy only) were randomized for either 3 months of VR training or no
      training. Basic VR performance and defined soft skills (self-efficacy, stress
      coping, and motivation) were assessed prior to randomization using basic modules
      of the VR simulator LapSim((r)) and standardized psychological questionnaires.
      Three months after randomization VR performance was reassessed. Outcome
      measurement was based on the results derived from the most complex of the basic
      VR modules ("diathermy cutting") as the primary end point. A correlation analysis
      of the VR end-point performance and the psychological scores was done in both
      groups. RESULTS: Structured VR training enhanced VR performance of surgical
      trainees. An additional correlation to high motivational states (P < 0.05) was
      found. Low levels of self-efficacy and negative stress-coping were related to
      poor VR performance in the untrained control group (P < 0.05). This correlation
      was absent in the trained intervention group (P > 0.05). CONCLUSION: Low self
      efficacy and negative stress-coping strategies seem to predict poor VR
      performance. However, structured training along with high motivational states is
      likely to balance out this impairment.

PMID- 21190110
TI  - Selection criteria for hepatectomy in patients with hepatocellular carcinoma
      classified as Child-Pugh class B.
AB  - BACKGROUND: The appropriate surgical approach for hepatocellular carcinoma (HCC)
      patients of Child-Pugh class B is unclear. The aim of this study was to clarify
      the prognostic factors after hepatectomy in Child-Pugh class B patients and to
      delineate the selection criteria for hepatectomy. METHODS: One hundred fifty
      patients of Child-Pugh class B who underwent hepatectomy were enrolled in this
      retrospective study (Hx group). Univariate and multivariate analyses were
      performed to identify prognostic factors. The prognosis was compared with that of
      23 patients of Child-Pugh class B who underwent liver transplantation (LT group).
      RESULTS: The overall survival rate of the Hx group was significantly worse than
      that of the LT group (5-year survival: 36.0 vs. 78.3%, p = 0.001). In
      multivariate analyses, diabetes mellitus (p = 0.011), preoperative total
      bilirubin level >= 1.5 mg/dl (p = 0.038), and Child-Pugh score of 8 or 9 (p =
      0.038) were independent prognostic factors. Although the overall 5-year survival
      rate of patients with none of the three adverse prognostic factors was only
      50.3%, that of patients with one or more adverse prognostic factors was only
      27.2% (p = 0.001). CONCLUSIONS: Hepatectomy may be the optimal initial treatment
      for HCC patients classified as Child-Pugh class B and without any adverse
      prognostic factors.

PMID- 21190111
TI  - Angiointervention: high rates of failure following blunt renal injuries.
AB  - BACKGROUND: Nonoperative management (NOM) of solid organ injury after blunt
      trauma is now standard. Recently, angioembolization (AE) has been used to extend
      NOM. Few data exist on evaluating NOM of blunt renal injuries (BRIs). We sought
      to determine the overall efficacy of NOM as well as the outcome of AE in patients
      with BRI. METHODS: The trauma registry was used to identify all patients with BRI
      between January 2002 and December 2008. Medical records were reviewed for
      demographics, grade of injury, use of angiographic intervention, and outcome.
      RESULTS: A total of 434 patients with BRI were identified, 416 of whom had
      planned NOM; 337 (81%) patients were successfully managed without further
      intervention for their BRI. In all, 79 (19%) patients underwent angiography; 22
      (27.8%) of these patients underwent AE, and 6 (27.2%) failed 1.2 +/- 0.8 days
      after AE. Patients who failed AE had a significantly higher blood transfusion
      requirement during the first 24 h of admission (p = 0.01). Seven patients not
      embolized failed 1.9 +/- 1.9 days after angiography. Thus, of the 79 patients
      having angiography, 13 (16.5%) failed and required laparotomy to treat their
      BRIs. Overall failure rate of NOM was 3.1% (13/416). Patients who failed
      angiography, with or without AE, required more blood during the first 24 h after
      admission (p = 0.03). CONCLUSIONS: NOM of BRI is safe and effective, with an
      overall failure rate of 3.1%. However, angiography with or without AE has
      substantial failure rates. Patients with higher-grade injuries and active
      vascular extravasation on admission computed tomography scan also fail NOM
      regardless of therapy. The blood transfusion requirement during the first 24 h
      may indicate who will require operative intervention following angiography. Close
      observation and/or early laparotomy are wise for these high-risk patients.

PMID- 21190113
TI  - Is entirely conservative management a correct strategy for hemodynamically stable
      patient with a grade IV blunt pancreatic injury?

PMID- 21190114
TI  - Validation of the World Health Organization tool for situational analysis to
      assess emergency and essential surgical care at district hospitals in Ghana.
AB  - BACKGROUND: The World Health Organization (WHO) Tool for Situational Analysis to
      Assess Emergency and Essential Surgical Care (hereafter called the WHO Tool) has
      been used in more than 25 countries and is the largest effort to assess surgical
      care in the world. However, it has not yet been independently validated. Test
      retest reliability is one way to validate the degree to which tests instruments
      are free from random error. The aim of the present field study was to determine
      the test-retest reliability of the WHO Tool. METHODS: The WHO Tool was mailed to
      10 district hospitals in Ghana. Written instructions were provided along with a
      letter from the Ghana Health Services requesting the hospital administrator to
      complete the survey tool. After ensuring delivery and completion of the forms,
      the study team readministered the WHO Tool at the time of an on-site visit less
      than 1 month later. The results of the two tests were compared to calculate kappa
      statistics for each of the 152 questions in the WHO Tool. The kappa statistic is
      a statistical measure of the degree of agreement above what would be expected
      based on chance alone. RESULTS: Ten hospitals were surveyed twice over a short
      interval (i.e., less than 1 month). Weighted and unweighted kappa statistics were
      calculated for 152 questions. The median unweighted kappa for the entire survey
      was 0.43 (interquartile range 0-0.84). The infrastructure section (24 questions)
      had a median kappa of 0.81; the human resources section (13 questions) had a
      median kappa of 0.77; the surgical procedures section (67 questions) had a median
      kappa of 0.00; and the emergency surgical equipment section (48 questions) had a
      median kappa of 0.81. CONCLUSIONS: Hospital capacity survey questions related to
      infrastructure characteristics had high reliability. However, questions related
      to process of care had poor reliability and may benefit from supplemental data
      gathered by direct observation. Limitations to the study include the small sample
      size: 10 district hospitals in a single country. Consistent and high correlations
      calculated from the field testing within the present analysis suggest that the
      WHO Tool for Situational Analysis is a reliable tool where it measures structure
      and setting, but it should be revised for measuring process of care.

PMID- 21190115
TI  - A rare presentation of crush injury: transanal small bowel evisceration. Case
      report and review of the literature.
AB  - Evisceration of the small intestine through the anus is an extremely rare event
      in children. We report a 2-year-old boy who sustained transanal small bowel
      evisceration associated with bilateral diaphragmatic rupture, left diaphragmatic
      herniation, and spinal cord injury without radiographic abnormality which
      happened after crushing by motor vehicle. We reviewed children with transanal
      small bowel evisceration and discussed etiological differences between children
      and adult. We also discussed the basic principles of management and follow up in
      these patients.

PMID- 21190116
TI  - Peoniflorin suppresses tumor necrosis factor-alpha induced chemokine production
      in human dermal microvascular endothelial cells by blocking nuclear factor-kappaB
      and ERK pathway.
AB  - Peoniflorin (PF) extracted from the root of Paeonia lactiflora pall displays anti
      inflammation and antioxidant properties in several animal models. Chemokines are
      vital for directing the movement of circulating leukocytes to the sites of
      inflammation and are involved in the pathogenesis of various inflammatory skin
      diseases. Herein, we investigated the effects and potential mechanisms of PF on
      tumor necrosis factor-alpha (TNF-alpha) induced chemokine production in human
      dermal microvascular endothelial cells. Human dermal microvascular endothelial
      cell line (HMEC-1) was treated by TNF-alpha with or without PF. PF markedly
      attenuated TNF-alpha-induced chemokines (including CCL2, CCL5, CCL20, CXCL8,
      CXCL16 and CX3CL1) mRNA expression in HMEC-1. PF also reduced the secretion of
      these chemokines in culture supernatants. In addition, endothelial activation in
      the presence of PF markedly blocked the chemotactic activities of TNF-alpha
      stimulated HMEC-1 supernatant on promyelocytic leukemia cell line (HL-60) or the
      acute mature monocytic leukemia cell line (THP-1) cell migration. Furthermore,
      Western blot data revealed TNF-alpha upregulated phosphorylation of inhibitor of
      kappaB-alpha (IkappaBalpha) and phosphorylation of extracellular signal-regulated
      kinase (ERK)1/2, which was almost completely reversed by PF. Finally, PF
      inhibited nuclear factor-kappaB (NF-kappaB) nuclear translocation to the nucleus.
      Taken together, our data provide the first evidence that PF has an anti
      inflammatory ability against TNF-alpha-induced chemokine production and leukocyte
      migration, which may be at least partly related to the inhibition of NF-kappaB
      and ERK pathway. PF may be a candidate medicine for the treatment of inflammatory
      skin diseases.

PMID- 21190118
TI  - Localization of plasminogen in mouse hippocampus, cerebral cortex, and
      hypothalamus.
AB  - Although the tissue plasminogen activator/plasminogen system contributes to
      numerous brain functions, such as learning, memory, and anxiety behavior, little
      attention has as yet been given to the localization of plasminogen in the brain.
      We have investigated the localization of plasminogen in the adult mouse brain by
      using immunohistochemistry. In the hippocampus, plasminogen immunoreactivity was
      seen in the pyramidal cell layer as numerous punctate structures in neuronal
      somata. An electron-microscopic study further demonstrated that the plasminogen
      immunoreactive punctate structures represented secretory vesicles and/or vesicle
      clusters. In the cerebral cortex, plasminogen immunoreactivity was evident in the
      somata of the layer II/III and V neurons. A quantitative analysis revealed that
      parvalbumin (PV)-positive neurons had more plasminogen-immunoreactive puncta
      compared with those of PV-negative neurons in the hippocampus and cerebral
      cortex. Plasminogen immunoreactivity was present throughout the hypothalamus,
      being particularly prominent in the neuronal somata of the organum vasculosum
      laminae terminalis, ventromedial preoptic nucleus, supraoptic nucleus,
      subfornical organ, medial part of the paraventricular nucleus (PVN), posterior
      part of the PVN, and arcuate hypothalamic nucleus. Thus, plasminogen is highly
      expressed in specific populations of hippocampal, cortical, and hypothalamic
      neurons, and plasminogen-containing vesicles are mainly observed at neuronal
      somata.

PMID- 21190117
TI  - Patterns of dye coupling involving serotonergic neurons provide insights into the
      cellular organization of a central complex lineage of the embryonic grasshopper
      Schistocerca gregaria.
AB  - All eight neuroblasts from the pars intercerebralis of one protocerebral
      hemisphere whose progeny contribute fibers to the central complex in the
      embryonic brain of the grasshopper Schistocerca gregaria generate serotonergic
      cells at stereotypic locations in their lineages. The pattern of dye coupling
      involving these neuroblasts and their progeny was investigated during
      embryogenesis by injecting fluorescent dye intracellularly into the neuroblast
      and/or its progeny in brain slices. The tissue was then processed for anti
      serotonin immunohistochemistry. A representative lineage, that of neuroblast 1-3,
      was selected for detailed study. Stereotypic patterns of dye coupling were
      observed between progeny of the lineage throughout embryogenesis. Dye injected
      into the soma of a serotonergic cell consistently spread to a cluster of between
      five and eight neighboring non-serotonergic cells, but never to other
      serotonergic cells. Dye injected into a non-serotonergic cell from such a cluster
      spread to other non-serotonergic cells of the cluster, and to the immediate
      serotonergic cell, but never to further serotonergic cells. Serotonergic cells
      tested from different locations within the lineage repeat this pattern of dye
      coupling. All dye coupling was blocked on addition of an established gap
      junctional blocker (n-heptanol) to the bathing medium. The lack of coupling among
      serotonergic cells in the lineage suggests that each, along with its associated
      cluster of dye-coupled non-serotonergic cells, represents an independent
      communicating pathway (labeled line) to the developing central complex neuropil.
      The serotonergic cell may function as the coordinating element in such a
      projection system.

PMID- 21190119
TI  - Endoscopic ultrasound-guided anterograde cholangiopancreatography.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) may fail in 10-15% of
      cases. A growing percentage of such cases are due to the inaccessible papilla
      after gastric bypass surgery for the treatment of obesity. Endoscopic
      ultrasonography (EUS) offers an alternative route of access to the bile and
      pancreatic ducts. Using the curved linear array echoendoscope, access to the bile
      and pancreatic ducts is possible under real-time EUS guidance. The route of
      access is 'anterograde', in contrast to the 'retrograde' approach of ERCP. We
      have coined the term "EUS-guided anterograde cholangiopancreatography (EACP)" to
      cover the spectrum of EUS-guided techniques for accessing and draining the bile
      and pancreatic ducts. These techniques are reviewed in this paper. The literature
      has validated the feasibility of EACP but complication rates have been high; the
      safety profile of EACP must improve. This will require tools, designed for EUS
      guided applications, that enable safer transenteric access and drainage.

PMID- 21190120
TI  - Cerebral cavernous malformations and intractable epilepsy: the limited usefulness
      of current literature.
AB  - BACKGROUND: Cerebral cavernous malformations (CCM) are known to be highly
      epileptogenic lesions. A number of studies on CCM surgery deal with CCM
      associated seizures and/or epilepsy. In order to counsel patients with CCM
      associated epilepsy, clear results from such studies would be highly useful. This
      study reviews the current literature with the aim to assess its usefulness for
      presurgical decision-making with emphasis on differentiating outcomes in
      different epilepsy types. METHODS: A systematic Medline search identified 27
      studies between 1991 and 2009 through the keywords "cavernomas, cavernous,
      hemangioma, AND epilepsy, AND surgery". They were analysed with regard to clarity
      of definition of epilepsy subtypes, precision of definition of drug-resistant
      epilepsy, information on surgical procedure and presurgical workup, seizure
      outcome and length of follow-up. RESULTS: Twenty studies included only surgically
      treated patients. Three types of epilepsy were defined: drug-resistant epilepsy,
      epilepsy or single/sporadic seizures. In 12 of 27 studies, at least one of these
      categories remained unclear. The classic definition of drug-resistant epilepsy
      was not used in the vast majority of studies, with many groups using their own
      definition. In 30%, the surgical procedure was not described precisely, although
      52% of studies used a differentiated preoperative evaluation. Seizure outcome was
      described using a widely accepted classification in only 48% of series, and in
      over half of the studies outcome results contained cases with insufficient length
      of follow-up. CONCLUSIONS: A large proportion of recent studies on surgery for
      CCM-associated epilepsy are not using criteria and definitions for the
      classification of epilepsy and outcome that are commonly used by epileptologists
      or epilepsy surgeons. This results in the limited usefulness of a large part of
      the literature for the purpose of preoperative counselling a patient with CCM
      associated epilepsy.

PMID- 21190121
TI  - Properties of metabolic substances produced by group A streptococcus from a food
      borne epidemic.
AB  - Here we report a large food poisoning outbreak by Streptococcus pyogenes that
      occurred in Kanagawa, Japan, in July 2005. To compare cases of type T-B3264
      (Chiba) and type T-28 (Tokyo) reported to date, we studied the properties and
      activity of the major virulence factors produced by Streptococcus pyogenes type T
      25 (Kanagawa): hemolysin, cysteine protease streptococcal pyrogenic exotoxin B
      (SpeB), and NAD glycohydrolase (NADase). These virulence factors were also
      analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).
      The titer of hemolysin was 9 50% hemolytic dose (HD(50)) per milliliter
      (HD(50)/ml) for T-25, 173 HD(50)/ml for T-28, and 147 HD(50)/ml for T-B3264. The
      hemolytic titer of T-25 was very low compared with those of T-28 and T-B3264.
      Each hemolysin produced by the three strains was dependent on its reductant, and
      its properties differed among strains. The major hemolysin of T-25 was identified
      as streptolysin O (SLO), because cholesterol or gamma-globulin, but not
      phospholipids, inhibited its hemolysis. In contrast, the major hemolysin of T-28
      and T-B3264 was streptolysin S (SLS). Although the SpeB activity of T-25 (4.8
      U/ml) was lower than that of T-B3264, its NADase activity (19.1 U) was the
      largest of the three strains. The conversion from the SpeB precursor to mature
      SpeB was confirmed by SDS-PAGE analysis of T-25 at 6 h of culture; no conversion
      was identified for T-28 and T-B3264 at 6 h. SpeB of T-25 was converted quickly,
      most likely because of the degradation of SLO by SpeB, thereby resulting in the
      very low hemolytic titer of T-25. These results suggest that the three strains
      have diverse properties and activities of major virulence factors. The specific
      interactions of these virulence factors are thought to be involved in the
      pathosis of these strains.

PMID- 21190122
TI  - Effects of endogenous substance P expression on degranulation in RBL-2H3 cells.
AB  - OBJECTIVE AND DESIGN: To determine whether RBL-2H3 cells have endogenous
      substance P (SP) expression under immunoglobulin E (IgE)-activated and
      inactivated conditions, and to ascertain the function of endogenous SP in the
      antigen-induced degranulation of RBL-2H3 cells. MATERIALS AND METHODS: SP mRNA
      and protein expression in both inactivated and 2,4-dinitrophenol (DNP)-specific
      IgE-activated RBL-2H3 cells were assessed by real-time PCR and
      immunofluorescence, respectively. Following activation with DNP-specific IgE, the
      degranulation of RBL-2H3 cells in response to DNP-bovine serum albumin (BSA),
      with and without endogenous SP expression, was assessed by monitoring the release
      of the granular enzyme beta-hexosaminidase. RESULTS: Endogenous SP mRNA and
      peptide expression increased in activated RBL-2H3 cells, compared with
      inactivated RBL-2H3 cells. The small hairpin RNA (shRNA)-mediated knockdown of
      endogenous SP reduced the degranulation ability of RBL-2H3 cells. CONCLUSIONS:
      Activated RBL-2H3 cells express endogenous SP which plays a role in antigen
      induced degranulation.

PMID- 21190123
TI  - Oxymatrine reduces neuronal cell apoptosis by inhibiting Toll-like receptor
      4/nuclear factor kappa-B-dependent inflammatory responses in traumatic rat brain
      injury.
AB  - OBJECTIVE: To investigate the influence of oxymatrine (OMT) on Toll-like receptor
      4 (TLR-4)/nuclear factor kappa-B (NF-kappaB)-dependent inflammatory responses and
      neuronal cell apoptosis after traumatic brain injury (TBI). MATERIALS AND
      METHODS: Wistar rats were given an intraperitoneal injection of 60 or 120 mg/kg
      OMT after TBI once a day till day 5. Rats were killed by decapitation at hours 2,
      6 and 12, and days 1, 2, 3 and 5 after TBI. Gene expressions of TLR-4 and NF
      kappaB, concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin
      1beta (IL-1beta) and interleukin-6 (IL-6) as well as the number of apoptotic
      neuronal cells in traumatic rat brain tissues were determined. RESULTS: The
      administration of 120 mg/kg OMT could significantly suppress gene expressions of
      TLR-4 and NF-kappaB, lessen concentrations of TNF-alpha, IL-1beta and IL-6, and
      reduce the number of apoptotic neuronal cells in traumatic rat brain tissues by
      the Mann-Whitney U test (P < 0.05), but the administration of 60 mg/kg OMT could
      not (P > 0.05). CONCLUSION: OMT may inhibit TLR4/NF-kappaB-dependent inflammatory
      responses, and furthermore lessen neuronal cell apoptosis after TBI.

PMID- 21190124
TI  - Effects of two different dosing regimens of terlipressin on organ functions in
      ovine endotoxemia.
AB  - OBJECTIVE AND DESIGN: To test the hypothesis that a continuous infusion of the
      vasopressin analog terlipressin is associated with less organ dysfunction as
      compared to intermittent bolus infusion in an ovine sepsis model. SUBJECTS:
      Twenty-seven adult female sheep. TREATMENT: All sheep were subjected to a
      Salmonella typhosa endotoxin infusion (10 ng/kg/min). After 16 h of endotoxemia,
      the surviving animals (n = 24) were randomized to (1) an untreated control group,
      (2) a continuous terlipressin group (2 mg/24 h), or (3) a terlipressin bolus
      group (1 mg/6 h). METHODS: Hemodynamic variables were measured and blood was
      withdrawn at specific time points for the assessment of organ functions. RESULTS:
      Continuous terlipressin infusion was associated with improved surrogate
      parameters of myocardial, renal, and hepatic function as compared with
      terlipressin bolus infusion. Reduced vascular hyperpermeability was evidenced by
      an attenuated decrease in plasma protein concentrations in sheep treated with
      continuous terlipressin infusion as compared to bolus injection or no treatment.
      CONCLUSIONS: Continuous infusion of low-dose terlipressin preserved several
      surrogate parameters of organ function better than intermittent bolus injections
      in sheep with systemic inflammation.

PMID- 21190125
TI  - Hypothermia in cardiogenic shock reduces systemic t-PA release.
AB  - Therapeutic hypothermia has been found to improve hemodynamic and metabolic
      parameters in cardiogenic shock. Tissue plasminogen activator (t-PA) is a pro
      thrombolytic enzyme, which also possesses pro-inflammatory properties.
      Interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) are pro
      inflammatory cytokines; interleukin 10 (IL-10) and transforming growth factor
      beta 1 (TGF-beta1) are anti-inflammatory cytokines. The aim of this experiment
      was to investigate the mechanism behind the protective effect of therapeutic
      hypothermia in cardiogenic shock. This was done by studying the effect of
      hypothermia on basal t-PA levels, peripheral t-PA release, and on the
      inflammatory response. Cardiogenic shock was induced by inflation of an
      angioplasty balloon in the proximal left anterior descending artery for 40 min in
      16 pigs, followed by 110 min of reperfusion. The animals were randomized to
      hypothermia (33 degrees C, n = 8), or normothermia (n = 8) at reperfusion.
      Hemodynamic parameters were continuously monitored. Plasma was sampled every 30
      min for analysis of blood-gases and t-PA, and for analysis of inflammatory
      markers at baseline and at the end of the experiment. t-PA, IL-6 and TGF-beta1
      increased during cardiogenic shock. Apart from favourably affecting hemodynamic
      and metabolic variables, hypothermia was found to reduce basal arterial and
      venous t-PA levels, and to inhibit the release of t-PA from the peripheral
      vascular bed. Hypothermia did not alter the inflammatory response. In conclusion,
      mild hypothermia improves hemodynamic and metabolic parameters in cardiogenic
      shock. This is associated with a reduction in basal t-PA levels and t-PA release
      from the peripheral vascular bed, but not with an altered inflammatory response.

PMID- 21190126
TI  - Erratum to: Letter to the Editor: The ongoing tyranny of statistical significance
      testing in biomedical research.

PMID- 21190128
TI  - Case management after long-term absence from work in China: a case report.
AB  - INTRODUCTION: Return-to-work (RTW) after occupational injuries is an important
      and challenging issue. Case managers are expected to play a vital role in
      successful RTW. In China, RTW intervention is in its early phase and requires
      further research and practice. OBJECTIVES: This case report describes Mr. H's RTW
      process for illustrating the work of a case management team in China. Suggestions
      on developing and optimizing the process in China are given. METHODS: After 9
      years of absence from work due to severe burn injuries at work, Mr. H was
      referred for RTW interventions. Mr. H received social and occupational
      rehabilitation services of 3 months, and the following workplace visits and work
      trials. After the job placement, the case manager continued the liaison with the
      worker and employer. RESULTS: Mr. H showed positive changes in occupational and
      social adjustment after the case management interventions. This was reflected
      from the shift from the contemplation to action stage on the Lam Assessment of
      Stages of Employment Readiness. Despite he did not show significant changes on
      functional capacity and fear avoidance beliefs, Mr. H passed the job credential
      test and was offered a maintenance technician position at a new company. Both the
      worker and the employer were satisfied with the outcome of the case management.
      CONCLUSIONS: The RTW interventions carried out by the case managers appeared to
      be effective within the Chinese system. The results suggested that professional
      training of case managers, RTW-related policies and technological standards,
      early integrated interventions should be further developed in China. Disability
      Adjustment Group Therapy and RTW Support Groups perhaps are useful approaches in
      workers' returning to work.

PMID- 21190129
TI  - A mesenchymal stromal cell line resistant to paclitaxel that spontaneously
      differentiates into osteoblast-like cells.
AB  - The mesenchymal stromal cell line SR-4987 has been established in our laboratory
      from the bone marrow of BDF/1 mice. Recent information on mesenchymal stem cells
      biology and the need to deal with well-characterized cell lines suggest to
      critically consider the existent data on this cell line by updating them with new
      investigations on growth parameters, in vitro plasticity, and drug sensitivity to
      anti-cancer, anti-inflammatory, and a histone deacetylase inhibitor. SR-4987
      cells show a population doubling time of 24.5 +/- 5.4 h, a plating efficiency of
      2.87 +/- 1.19%, and under stimulation maintain only in part their multipotency by
      differentiating towards chondro-osteogenic lineages but not into adipogenic.
      Surprisingly, these mesenchymal stromal cells differentiate spontaneously into
      osteoblast-like cells and this is significantly stimulated by valproic acid. SR
      4987 cells show a dramatic resistance to paclitaxel (PTX) with a resistance index
      of 39.6 times (evaluated versus MOLT-4 leukemia) and of 68.2 (versus HT-29
      colorectal carcinoma). SR-4987 resistance is reversed by verapamil and correlates
      with high expression of P-glycoprotein that is down-modulated by PTX. Taken
      together, our results indicated that SR-4987 line is a very interesting cell
      model useful to investigate both drug sensitivity resistance and
      physiopathological aspects related to mesenchymal cell function.

PMID- 21190131
TI  - Foreword. Biophysics in chromatin structure and nuclear dynamics.

PMID- 21190130
TI  - Chromosomes and cancer cells.
AB  - Two prominent features of cancer cells are abnormal numbers of chromosomes
      (aneuploidy) and large-scale structural rearrangements of chromosomes. These
      chromosome aberrations are caused by genomic instabilities inherent to most
      cancers. Aneuploidy arises through chromosomal instability (CIN) by the
      persistent loss and gain of whole chromosomes. Chromosomal rearrangements occur
      through chromosome structure instability (CSI) as a consequence of improper
      repair of DNA damage. The mechanisms that cause CIN and CSI differ, but the
      phenotypic consequences of aneuploidy and chromosomal rearrangements may overlap
      considerably. Both CIN and CSI are associated with advanced stage tumors with
      increased invasiveness and resistance to chemotherapy, indicating that targeted
      inhibition of these instabilities might slow tumor growth. Here, we review recent
      efforts that define the mechanisms and consequences of CIN and CSI.

PMID- 21190132
TI  - Combining FISH with localisation microscopy: Super-resolution imaging of nuclear
      genome nanostructures.
AB  - The optical resolution of conventional far field fluorescence light microscopy is
      restricted to about 200 nm laterally and 600 nm axially and has been thought for
      many decades to be an insurmountable barrier for the quantitative spatial
      analysis of cellular and hence also nuclear constituents. Novel approaches in
      light microscopy have now overcome this barrier. Here, we report on a special
      method of localisation microscopy, spectral precision distance/position
      determination microscopy and its combination with fluorescence in situ
      hybridization to analyse the spatial distribution of specific DNA sequences in
      human cell nuclei at the macromolecular optical resolution level. As an example,
      repetitive DNA sequence DYZ2 located within the heterochromatin region on human
      chromosome Yq12 was labelled with clone pHY2.1. Between 300 and 700 single-probe
      molecules were resolved in individual chromatin domains, corresponding to a
      detected molecule density around 500/MUm(2), i.e., many times higher than
      resolvable by conventional fluorescence microscopy. A mean localisation accuracy
      of about 20 nm indicated a mean optical resolution in the 50 nm range. Beyond new
      perspectives for light microscopic studies of specific chromatin nanostructures,
      this may open a new avenue towards the general analysis of copy number of
      specific DNA sequences in small regions of individual interphase nuclei.

PMID- 21190133
TI  - Structure determination of genomic domains by satisfaction of spatial restraints.
AB  - The three-dimensional (3D) architecture of a genome is non-random and known to
      facilitate the spatial colocalization of regulatory elements with the genes they
      regulate. Determining the 3D structure of a genome may therefore probe an
      essential step in characterizing how genes are regulated. Currently, there are
      several experimental and theoretical approaches that aim at determining the 3D
      structure of genomes and genomic domains; however, approaches integrating
      experiments and computation to identify the most likely 3D folding of a genome at
      medium to high resolutions have not been widely explored. Here, we review
      existing methodologies and propose that the integrative modeling platform
      (http://www.integrativemodeling.org), a computational package developed for
      structurally characterizing protein assemblies, could be used for integrating
      diverse experimental data towards the determination of the 3D architecture of
      genomic domains and entire genomes at unprecedented resolution. Our approach,
      through the visualization of looping interactions between distal regulatory
      elements, will allow for the characterization of global chromatin features and
      their relation to gene expression. We illustrate our work by outlining the recent
      determination of the 3D architecture of the alpha-globin domain in the human
      genome.

PMID- 21190134
TI  - Stepwise aromatic nucleophilic substitution in continuous flow. Synthesis of an
      unsymmetrically substituted 3,5-diamino-benzonitrile library.
AB  - Aromatic or heteroaromatic ring precursors with 2-3 identical functionalities are
      often used in sequential derivatization depending on the reactivity difference or
      the selective execution of the reaction such as nucleophilic aromatic
      substitution. Continuous flow chemistry offers an enhanced parameter space
      (pressure and temperature) with rapid parameter optimization that ensures
      selectivity in many cases. We developed a flow chemistry procedure to carry out a
      stepwise aromatic nucleophilic substitution of difluoro-benzenes having an
      activating group in meta position to the fluorines. The mono-aminated products
      were obtained in high yield and selectivity in an extremely short reaction time,
      while applying higher temperature, longer reaction zone (or time), and employing
      higher excess of another amine reactant, the subsequent introduction of the
      second amino group was also successfully achieved leading to an unsymmetrically
      substituted 3,5-diamino-benzonitrile library.

PMID- 21190135
TI  - Interactions between CCM and N2 fixation in Trichodesmium.
AB  - In view of the current increase in atmospheric pCO(2) and concomitant changes in
      the marine environment, it is crucial to assess, understand, and predict future
      responses of ecologically relevant phytoplankton species. The diazotrophic
      cyanobacterium Trichodesmium erythraeum was found to respond strongly to elevated
      pCO(2) by increasing growth, production rates, and N(2) fixation. The magnitude
      of these CO(2) effects exceeds those previously seen in other phytoplankton,
      raising the question about the underlying mechanisms. Here, we review recent
      publications on metabolic pathways of Trichodesmium from a gene transcription
      level to the protein activities and energy fluxes. Diurnal patterns of
      nitrogenase activity change markedly with CO(2) availability, causing higher diel
      N(2) fixation rates under elevated pCO(2). The observed responses to elevated
      pCO(2) could not be attributed to enhanced energy generation via gross
      photosynthesis, although there are indications for CO(2)-dependent changes in
      ATP/NADPH + H(+) production. The CO(2) concentrating mechanism (CCM) in
      Trichodesmium is primarily based on HCO(3)(-) uptake. Although only little CO(2)
      uptake was detected, the NDH complex seems to play a crucial role in internal
      cycling of inorganic carbon, especially under elevated pCO(2). Affinities for
      inorganic carbon change over the day, closely following the pattern in N(2)
      fixation, and generally decrease with increasing pCO(2). This down-regulation of
      CCM activity and the simultaneously enhanced N(2) fixation point to a shift in
      energy allocation from carbon acquisition to N(2) fixation under elevated pCO(2)
      levels. A strong light modulation of CO(2) effects further corroborates the role
      of energy fluxes as a key to understand the responses of Trichodesmium.

PMID- 21190136
TI  - Oxygenic photosynthesis and the distribution of chloroplasts.
AB  - The integrated functioning of two photosystems (I and II) whether in
      cyanobacteria or in chloroplasts is the outstanding sign of a common ancestral
      origin. Many variations on the basic theme are currently evident in oxygenic
      photosynthetic organisms whether they are prokaryotes, unicellular, or
      multicellular. By conservative estimates, oxygenic photosynthesis has been around
      for at least ca. 2.2-2.7 billions years, consistent with cyanobacteria-type
      microfossils, biomarkers, and an atmospheric rise in oxygen to less than 1.0% of
      the present concentration. The presumptions of chloroplast formation by the
      cyanobacterial uptake into a eukaryote prior to 1.6 BYa ago are confounded by
      assumptions of host type(s) and potential tolerance of oxygen toxicity. The
      attempted dating and interrelationships of particular chloroplasts in various
      plant or animal lineages has relied heavily on phylogenomic analysis and
      evaluations that have been difficult to confirm separately. Many variations occur
      in algal groups, involving the type and number of accessory pigments, and the
      number(s) of membranes (2-4) enclosing a chloroplast, which can both help and
      complicate inferences made about early or late origins of chloroplasts.
      Integration of updated phylogenomics with physiological and cytological
      observations remains a special challenge, but could lead to more accurate
      assumptions of initial and extant endosymbiotic event(s) leading toward stable
      chloroplast associations.

PMID- 21190137
TI  - The biological and geological contingencies for the rise of oxygen on Earth.

PMID- 21190138
TI  - Some psychometric properties of the Pediatric Quality of Life InventoryTM Version
      4.0 Generic Core Scales (PedsQLTM) in the general Serbian population.
AB  - PURPOSE: The aim of this study was to evaluate the general measurement properties
      of the Serbian version of the Pediatric Quality of Life InventoryTM Version 4.0
      Generic Core Scales (PedsQLTM) self-report versions for children and adolescents
      (8-18 years). METHODS: The PedsQLTM was completed by 238 children and
      adolescents. The version was descriptively analyzed first. Afterward, internal
      consistency and construct and convergent validity were analyzed using the classic
      test theory psychometrical procedures. RESULTS: The PedsQLTM scale score means
      ranged 70.65-88.34, with the total score was 80.74. Scale internal consistency
      reliability determined by Cronbach's coefficient was above 0.7 for all except the
      School, 0.65, and Emotional Functioning Scale, 0.69. The statistics assessing the
      adequacy of the model in confirmatory factor analysis revealed poor model fit for
      the current structure of the PedsQLTM. Finally, the PedsQLTM total and
      psychosocial health showed convincing negative correlations with emotional and
      conduct problems, hyperactivity/inattention, and peer relationship problems.
      CONCLUSIONS: The Serbian PedsQLTM scales have appropriate internal consistency
      reliability, sufficient for group evaluations, and good convergent validity
      against psychological constructs. However, there are problems regarding its
      current construct validity (factorial validity).

PMID- 21190139
TI  - Dietary supplementation of boron differentially alters expression of borate
      transporter (NaBCl) mRNA by jejunum and kidney of growing pigs.
AB  - Inorganic boron (B), in the form of various borates, is readily absorbed across
      gastrointestinal epithelia. Although there is no stated B requirement, dietary B
      supplementation is thought to positively affect animal growth and metabolism,
      including promotion of bone strength and cell proliferation. Because of effective
      homeostatic control of plasma B levels, primarly by renal excretion, B toxicity
      in animals and humans is rare. The mechanisms responsible for improved animal
      performance and borate homeostasis are incompletely understood. Although a Na+
      coupled borate transporter (NaBC1) has been identified, the effect of dietary B
      supplementation on expression of NaBCl has not been evaluated. An experiment was
      conducted with growing pigs to determine if NaBC1 mRNA was expressed by small
      intestinal epithelia and kidney of growing barrows and whether dietary B (as
      borate) supplementation would affect expression of NaBC1 mRNA. A concomitant
      objective was to test the hypothesis that B supplementation of a phosphorus (P)
      deficient diet would improve calcium, phosphorus, or nitrogen retention. Twenty
      four crossbred growing barrows (body weight=74.0+/-9.8 kg) were selected and used
      in a randomized complete block design experiment with a total of eight blocks and
      three B supplementation treatments (n=8/treatment). A typical corn-soybean meal
      basal diet (calculated to contain 41 mg intrinsic B/kg) was formulated to meet or
      exceed nutrient requirements, except for P, and fed to all pigs for 12 days. The
      basal diet plus 0, 50, or 100 mg/kg of B (prilled sodium borate pentahydrate,
      Na2B4O7.5H2O) was then fed for 18 more days. Feces and urine were collected
      during days 6 to 16 of the B supplementation, and pigs were killed for collection
      of jejunal and ileal epithelia and kidney tissue. Real-time reverse transcription
      PCR analysis revealed that NaBC1 mRNA was expressed by these tissues, a novel
      finding for jejunal and ileal epithelia. Boron supplementation increased jejunal,
      but decreased, renal NaBC1 mRNA expression, relative to the 0 mg/kg treatment.
      The finding that NaBC1 mRNA is regulatable by dietary B is novel. That B
      supplementation evoked opposite effects on jejunal and kidney NaBC1 mRNA
      expression indicates that transcriptional regulation of NaBC1 expression may
      constitute a part of the homeostatic control of B metabolism. In contrast to its
      effect on NaBC1 mRNA expression, B supplementation did not affect total tract
      digestibility or retention of phosphorus, calcium, or nitrogen.

PMID- 21190140
TI  - Evaluation of toxic risk assessment of arsenic in male subjects through drinking
      water in southern Sindh Pakistan.
AB  - The arsenic (As) hazardous quotient was estimated based on concentration of As in
      drinking water and scalp hair of male subjects of two age groups (n=360)
      consuming As contaminated water at different levels and non-contaminated drinking
      water. The total As concentrations in drinking water of less-exposed (LE) and
      high-exposed (HE) areas was found to be 3- to 30-fold higher than the permissible
      limit of the World Health Organization (2004) for drinking water, while the
      levels of As in drinking water of non-exposed (NE) areas was within the
      permissible limit. The levels of As in scalp hair samples of male subjects of two
      age groups belonging to NE, LE, and HE areas ranged from 0.01 to 0.27, 0.11-1.31,
      and 0.36-6.80 MUg/g, respectively. A significant correlation between As contents
      of drinking water and As concentration in scalp hair was observed in sub-district
      Gambit (r=0.825-0.852, p<0.001) as compared to those subjects belonging to LE sub
      district Thari Mirwah. A toxicity risk assessment provides a hazard quotient
      corresponding to <10 that indicates non-carcinogenic exposure risk of understudy
      areas.

PMID- 21190142
TI  - The role of transplantation in diffuse large B-cell lymphoma: the impact of
      rituximab plus chemotherapy in first-line and relapsed settings.
AB  - Rituximab has improved the prognosis of patients with diffuse large B-cell
      lymphoma, but a high proportion of patients with advanced disease will relapse or
      will fail to achieve a remission with front-line treatment. Salvage chemotherapy,
      followed by high-dose chemotherapy or radiation therapy and autologous stem cell
      transplantation, remains the best treatment option for such patients, especially
      those who retain chemosensitivity. Allogeneic transplantation is under
      investigation in this setting, often as a treatment for relapse after autologous
      transplantation. Treatment-related mortality due to graft-versus-host disease,
      preparative regimen toxicity, and poor immune recovery often limits its benefits.
      This article reviews the role of hematopoietic stem cell transplantation in the
      treatment of diffuse large B-cell lymphoma, the incorporation of rituximab, and
      avenues of clinical investigation in this rapidly evolving field.

PMID- 21190144
TI  - A slip connecting the peroneus longus and tibialis posterior tendons at the
      forefoot: MRI, anatomic, and histologic findings in a cadaver.
AB  - The anatomy of the peroneus longus and tibialis posterior tendons is well    
      described in literature from both anatomy and radiology. Though a slip    
      connecting these two structures is described in the anatomic literature, its    
      existence has not been confirmed with magnetic resonance imaging (MRI). In this  
      study in a cadaver, such a connection is documented using high-resolution MRI  
      with anatomic and histologic correlation. This connection can provide support
      to     the Lisfranc joint complex and further stabilize the region of the first
      and     second metatarsal bases.

PMID- 21190143
TI  - Kaposiform hemangioendothelioma of the spleen in an adult: an initial case
      report.
AB  - Kaposiform hemangioendothelioma (KHE) is a rare locally aggressive vascular
      neoplasm characterized by infiltrating nodules and sheets of spindle cells, and
      unmistakable resemblance to Kaposi's sarcoma. KHE occurs mainly in newborns and
      infants and presents most commonly in the skin, deep soft tissue, and bone. We
      report a case of KHE in a 36-year-old female who presented with a spleen mass and
      underwent splenectomy. Macroscopic examination revealed a large, dark-red, firm
      mass in the spleen. Histologically, the tumor consisted of irregular,
      infiltrating nodules of densely packed spindle-shaped tumor cells closely
      associated with small slit-like and sieve-like blood vessels, which were
      separated with hyalinized hypocellular fibrous stroma. Immunohistochemically,
      both spindle and epithelioid cells were positive for CD34, CD31, and vimentin,
      but negative for EMA, cytokeratin, CD21, CD35, CD1a, and S-100 protein. The well
      formed capillaries and mature vessels but not spindle tumor cell showed
      reactivity for factor VIII- related antigen. Alpha-Smooth muscle actin was
      detected in pericytes surrounding small round or slit-like capillaries. The final
      histologic diagnosis was KHE. Follow-up 6 month after operation revealed no sign
      of recurrence or metastasis.To the best of our knowledge, this is the first
      report of KHE arising in the spleen.

PMID- 21190145
TI  - [Tobacco smoking and struggle against the smoking addiction--a look at Iran and
      other countries in the Persian Gulf region].

PMID- 21190146
TI  - [World Spirometry Day].

PMID- 21190141
TI  - NO orchestrates the loss of synaptic boutons from adult "sick" motoneurons:
      modeling a molecular mechanism.
AB  - Synapse elimination is the main factor responsible for the cognitive decline
      accompanying many of the neuropathological conditions affecting humans. Synaptic
      stripping of motoneurons is also a common hallmark of several motor pathologies.
      Therefore, knowledge of the molecular basis underlying this plastic process is of
      central interest for the development of new therapeutic tools. Recent advances
      from our group highlight the role of nitric oxide (NO) as a key molecule
      triggering synapse loss in two models of motor pathologies. De novo expression of
      the neuronal isoform of NO synthase (nNOS) in motoneurons commonly occurs in
      response to the physical injury of a motor nerve and in the course of amyotrophic
      lateral sclerosis. In both conditions, this event precedes synaptic withdrawal
      from motoneurons. Strikingly, nNOS-synthesized NO is "necessary" and "sufficient"
      to induce synaptic detachment from motoneurons. The mechanism involves a
      paracrine/retrograde action of NO on pre-synaptic structures, initiating a
      downstream signaling cascade that includes sequential activation of (1) soluble
      guanylyl cyclase, (2) cyclic guanosine monophosphate-dependent protein kinase,
      and (3) RhoA/Rho kinase (ROCK) signaling. Finally, ROCK activation promotes
      phosphorylation of regulatory myosin light chain, which leads to myosin
      activation and actomyosin contraction. This latter event presumably contributes
      to the contractile force to produce ending axon retraction. Several findings
      support that this mechanism may operate in the most prevalent neurodegenerative
      diseases.

PMID- 21190147
TI  - [Diagnostic value of induced sputum in interstitial lung disease].
AB  - BACKGROUND: Induced sputum (IS) has been recently used to investigate pulmonary
      inflammation in patients with interstitial lung disease (ILD), but still little
      attention has been paid to its efficacy in diagnosing sarcoidosis and other ILD.
      The aim of this study was to evaluate the diagnostic value of IS differential
      cell count and CD4+/CD8+ ratio in sarcoidosis (SA) and nonsarcoidosis ILD (NSA
      ILD). MATERIAL AND METHODS: We studied prospectively newly diagnosed 59 patients:
      36 SA and 23 NSA ILD [16 hypersensitivity pneumonitis (HP) and 7 idiopathic
      pulmonary fibrosis (IPF)]. IS was performed by inhaling a 5% NaCl solution for 4
      periods of 5 minutes. Giemsa stained cytopreps were differentially counted and T
      lymphocyte subsets were analyzed by flow cytometry method. The k-nearest
      neighbour rule (k-NN) or predictive value of CD4+/CD8+ ratio were used to
      discriminate between SA and NSA ILD. The variables of IS used in k-NN rule were:
      cells viability, total cell count, percentages of alveolar macrophages,
      lymphocytes, neutrophils, eosinophils, CD4+ and CD8+ subsets, and CD4+/CD8+
      ratio. RESULTS: 33 patients were able to produce an adequate sputum sample (SA
      15, HP-11, IPF-7). A CD4+/CD8+ ratio>2.6 had a sensitivity of 100% and a
      specificity of 72% with 84% of correctly classified cases in distinguishing SA
      from NSA ILD. However, using k-NN rule the probability of correct classification
      was 79% (classification error rate-21%). CONCLUSION: To distinguish SA from NSA
      ILD cut off CD4+/CD8+ ratio>2.6 alone was superior to k-NN rule using all the
      parameters of IS.

PMID- 21190148
TI  - [Smoking habits among women over 30 years old in Malopolska].
AB  - INTRODUCTION: The aim of the study was to estimate smoking habits and their
      intensity among women from urban and rural residents of Malopolska voivodship.
      MATERIAL AND METHODS: A structured questionnaire was used by trained nurses who
      conducted personal interview. Questions regarding smoking referred to age of
      starting smoking, duration of smoking, average daily number of cigarettes smoked.
      The total number of collected interviews was 840. Lifetime exposure to cigarette
      smoking was expressed in pack-years. RESULTS: Data were collected among 602 urban
      and 238 rural women from Malopolska voivodship. In Malopolska, there are 23.4%
      current smokers among women, 21.7% are ex-smokers, and about 55% never smoked.
      The percentage of never smokers in women is significantly higher among the rural
      women group (67.3%) than urban women group (50.0%). Currently smoking are 25.9%
      urban inhabitans and 17.2% women from rural population. There were no significant
      differences in smoking habits among younger group of women (below 50 years)
      living in urban and rural areas. CONCLUSION: The present results indicate that
      female population in urban and rural areas need effective educational strategy
      associated with presenting negative consequences of tobacco smoking and support
      in quitting the addiction.

PMID- 21190149
TI  - The prevalence of smoking among the population in the city of Mashhad (north east
      of Iran) and pulmonary function tests among smokers.
AB  - INTRODUCTION: Smoking is known as a major cause of chronic obstructive pulmonary
      disease (COPD). In this study the prevalence of smoking in the population of
      Mashhad city was evaluated as well as pulmonary function tests (PFTs) of smokers.
      MATERIAL AND METHODS: The prevalence of smoking was studied using a standard
      questionnaire. Pulmonary function tests, including forced vital capacity (FVC),
      forced expiratory volume in one second (FEV1), maximal mid-expiratory flow
      (MMEF), peak expiratory flow (PEF), and maximal expiratory flow at 75%, 50%, and
      25% of the FVC (MEF75,50,25), were measured in all smokers. RESULTS: In total,
      1435 individuals were interviewed including 999 males and 436 females. The number
      of smokers among the interviewed individuals was 183 (12.7%) including 172 male
      (17.2%) and 11 female (2.5%). The results showed that all values of PFTs in
      smokers were reduced. There were significant negative correlations between
      smoking duration and rate as pack/year and values of PFT (p<0.05). CONCLUSIONS:
      In this study the prevalence of smoking in the population of Mashhad city was
      shown for the first time. The effect of smoking on PFTs showed that smoking leads
      to constriction of large and medium airways, which is due to duration and rate of
      smoking.

PMID- 21190150
TI  - [Psychiatric and psychological complications in obstructive sleep apnea
      syndrome].
AB  - It is estimated, that symptoms of obstructive sleep apnea syndrome (OSAS) affect
      2 to 4% of the middle-aged population and their prevalence increases with age
      (over 50% people aged 65 and older suffer from OSAS). Among risk factors of OSAS
      we can distinguish: the male sex, race, overweight and obesity, thyroid
      hypofunction, age and alcohol abuse. Obstructive sleep apnea results in the
      absence (apnea) or reduction (hypopnea) of airflow lasting at least 10 s despite
      normal respiratory exertion. The apnea and hypopnea result in decreased oxygen
      saturation levels in the blood (hypoxemia). A number of consequences of OSAS can
      appear including: disruption of the sleep cycle, fragmentation of the sleep
      cycle, sleepiness, fatigue, headaches, cognitive impairments, irritability and
      mood disturbance, the higher risk of accidents at work and car accidents, the
      decrease of the quality of life and the higher risk of cardiovascular diseases.
      Besides various psychiatric and psychological complications presented in this
      review can occur in obstructive sleep apnea syndrome.

PMID- 21190151
TI  - [Treatment of chronic obstructive pulmonary disease--traditional
      bronchodilatation and targeted anti-inflammatory therapy].
AB  - Currently available pharmacological treatment of COPD relies mostly on
      prophylaxis (smoking cessation) and symptomatic treatment, i.e. inhaled
      anticholinergic agents, beta2-agonists and phosphodiesterase inhibitors, aiming
      in their bronchodilatation capacity. Inhaled corticosteroid therapy is mainly
      prescribed in far advanced stages of the disease and its role in disease
      modification is still controversial. The authors analize currently available
      treatment modalities with regards to their potential anti-inflammatory and
      pleiotropic mode of action, which may lead to disease course modification.

PMID- 21190152
TI  - [Exercise-induced bronchoconstriction].
AB  - Terms exercise-induced asthma (EIA) or exercise-induced bronchoconstriction (EIB)
      are used to describe transient bronchoconstriction occurring during or
      immediately after vigorous exercise in some subjects. For the diagnosis of EIB it
      is necessary to show at least 10% decrease in FEV1 from baseline following
      physical exercise. The prevalence of EIB has been reported to be 12-15% in
      general population, 10-20% in summer olympic athletes, affecting up to 50-70% of
      winter athletes (particularly ski runners and skaters). There are two key
      theories explaining EIB: thermal and osmotic. Differential diagnosis of EIB
      should include chronic cardio-pulmonary diseases, vocal cord dysfunction,
      hyperventilation syndrome and poor physical fitness or overtraining. According to
      the ATS guidelines from 1999 for the diagnosis of EIB a standardized exercise on
      a treadmill or cycle ergometer test with stable environmental conditions
      regarding temperature and humidity of inhaled air, should be employed. Other
      laboratory tests assessing bronchial hyperresponsiveness to indirect stimuli
      including eucapnic voluntary hyperpnea (EVH), mannitol, hypertonic saline, AMP or
      measurement of exhaled nitric oxide (FENO) are also successfully used. In the
      prevention of EIB include both pharmacologic and non-pharmacologic treatment. In
      patients with poorly controlled asthma intensification of anti-inflammatory
      treatment can decrease the frequency and severity of EIB. Short and long acting
      beta2-agonists, antileukotriene drugs can be used prior to exercise to prevent
      EIB.

PMID- 21190153
TI  - Marked improvement of heart failure upon adequate titration of continuous
      positive airway pressure in a patient with obstructive sleep apnea.
AB  - Sleep disordered breathing (SDB) is frequently present in heart failure (HF), and
      it may take the form of obstructive (OSA) and central (CSA) sleep apnea. The use
      of continuous positive airway pressure (CPAP) in patients with OSA and HF is
      associated with an improved neuroendocrine profile and cardiac function. The
      degree of upper airway obstruction and the airway closing pressure (and the PAP
      pressure used to relieve it) may all be highly variable in a setting of
      uncontrolled HF, mostly due to variable airway oedema. We present a case of a man
      with HF whose cardiac symptoms radically improved after adequate treatment of his
      OSA with an auto-adjusting PAP device.

PMID- 21190154
TI  - [Drug-induced hypersensitivity syndrome--a literature review and the case
      report].
AB  - Drug-induced hypersensitivity syndrome (DIHS) is characterized by fever, rash and
      internal organ involvement, mostly in form of hepatitis, myocarditis, nephritis
      or pneumonitis, which may occur 1-8 weeks after medicine exposure. Fever is an
      early feature, usually preceding a widespread erythematous skin eruption, but the
      severity of the skin-related changes does not correlate with the extent of
      internal organ involvement. It is considered that anticonvulsants (particularly
      carbamazepine), antibiotics, allopurinol are the most frequent causative agents
      of DIHS. The underlying mechanisms causing DIHS are poorly understood--defective
      detoxification of the reactive drug's metabolites or genetic predisposition have
      been implicated. Diagnosis of DIHS is based on clinical presentation connected
      with drug intake, supported by a finding of eosinophilia, increased concentration
      of inflammation markers and abnormal biochemical parameters, mainly liver
      function tests. Treatment consists of immediate withdrawal of all suspected
      medicines, followed by supportive systemic corticosteroids. We describe a case of
      a 72-years-old female who developed symptoms of drug-induced hypersensitivity
      syndrome after approximately 4 weeks of taking anticonvulsant (Amizepin) due to
      sensual axonal polyneuropathy. Withdrawal of drug and treatment with systemic
      corticosteroids caused clinical improvement rapidly.

PMID- 21190155
TI  - [Pneumonia in adult--diagnostic imaging].

PMID- 21190159
TI  - Hepatitis C recurrence: influence of serum cholesterol levels and liver steatosis
      on antiviral therapy.

PMID- 21190171
TI  - In vitro labeling of hydroxyapatite minerals by an engineered protein.
AB  - Biological and biomimetic synthesis of inorganics have been a major focus in hard
      tissue engineering as well as in green processing of advanced materials. Among
      the minerals formed by organisms, calcium phosphate mineralization is studied
      extensively to understand the formation of mineral-rich tissues. Herein, we
      report an engineered fusion protein that not only targets calcium phosphate
      minerals but also allows monitoring of biomineralization. To produce the bi
      functional fusion protein, nucleotide sequence encoding combinatorially selected
      hydroxyapatite-binding peptides (HABP) was genetically linked to the 3' end of
      the open reading frame of green fluorescence protein (GFPuv) and successfully
      expressed in Escherichia coli. The fluorescence and binding activities of the bi
      functional proteins were characterized by, respectively, using fluorescence
      microscopy and quartz crystal microbalance spectroscopy. The utility of GFPuv
      HABP fusion protein was assessed for both time-wise monitoring of mineralization
      and the visualization of the mineralized tissues. We used an alkaline phosphatase
      based reaction to control phosphate release, thereby mimicking biological
      processes, to monitor calcium phosphate mineralization. The increase in mineral
      amount was observed using the fusion protein at different time points. GFPuv
      HABP1 was also used for efficient fluorescence labeling of mineralized regions on
      the extracted human incisors. Our results demonstrate a simple and versatile
      application of inorganic-binding peptides conjugated with bioluminescence
      proteins as bi-functional bioimaging molecular probes that target mineralization,
      and which can be employed to a wide range of biomimetic processing and cell-free
      tissue engineering.

PMID- 21190177
TI  - Stability of a guest protein depends on stability of a host protein in
      insertional fusion.
AB  - Insertional fusion between host and guest protein domains has been employed to
      create multi-domain protein complexes displaying integrated and coupled
      functionalities. The effects of insertional fusion on the stability of a guest
      protein are however rather controversial. In the study described here, we
      examined whether the stability of inserted TEM1 beta-lactamase (BLA), as a guest
      protein, might be affected by the stability of a maltodextrin-binding protein
      (MBP), as a host protein. Our results indicate that expression levels and in
      vitro stability of the BLA domain were significantly higher when inserted into
      thermophilic MBP from Pyrococcus furiosus (PfMBP) compared to mesophilic MBP from
      Escherichia coli (EcMBP). Moreover, insertion into PfMBP at selected sites was
      found to improve thermal stability of the BLA domain without compromise in
      expression levels and BLA activity. Kinetic stabilization during prolonged
      thermal denaturation of the BLA domain was not guaranteed by insertion into
      PfMBP, but rather relied on the insertion sites. Taken together, we provide
      evidence that (i) the stability of the guest protein depended on the stability of
      the host protein in insertional fusion and (ii) insertion into PfMBP, at least at
      selected locations, can serve as a novel method of improving protein thermal
      stability.

PMID- 21190179
TI  - Temporally- and spatially regulated generation of distinct descendants by sonic
      hedgehog-expressing progenitors in the forebrain.
AB  - The generation of distinct neural subtypes depends on the activities of cell
      extrinsic and -intrinsic factors during the development of the vertebrate CNS.
      Previous studies have provided a molecular basis for how neural progenitors are
      patterned and generate distinct descendants that are spatially and temporally
      regulated by inductive signals secreted by polarized sources. However, it still
      remains unknown how the generation of neural descendants by progenitors located
      at polarized sources of inductive signals is controlled. Sonic hedgehog (Shh),
      which is expressed at the ventral midline in the forebrain, has been shown to
      play a critical role for the patterning and specification of distinct neural
      subtypes in the forebrain. Here, we analyzed the identities and distributions of
      Shh-descendants generated at discrete time points in the forebrain by using a
      ShhcreER(T2) mouse driver line in which a tamoxifen-inducible Cre cassette was
      inserted into the Shh locus together with a Z/EG mouse reporter line. Our results
      showed that Shh-expressing neural progenitors generated neuronal and glial
      descendants distributed throughout the telencephalon and diencephalon in a
      temporally distinct manner. Furthermore, our results showed that Shh-progenitors
      are located at two spatially distinct sub-domains that can be characterized by
      their temporally distinct patterns of Shh expression. These results suggest that
      temporally- and spatially controlled mechanisms that specify neural subtypes
      operate in the Shh-expressing progenitor domain, and raise the possibility that
      the distinct temporal gradient of Shh activity might be responsible for the
      generation of distinct neural subtypes in the telencephalon.

PMID- 21190182
TI  - Surface chemistry of metal-organic frameworks at the liquid-solid interface.
AB  - Metal-organic frameworks (MOFs) are a fascinating class of novel inorganic
      organic hybrid materials. They are essentially based on classic coordination
      chemistry and hold much promise for unique applications ranging from gas storage
      and separation to chemical sensing, catalysis, and drug release. The evolution of
      the full innovative potential of MOFs, in particular for nanotechnology and
      device integration, however requires a fundamental understanding of the formation
      process of MOFs. Also necessary is the ability to control the growth of thin MOF
      films and the positioning of size- and shape-selected crystals as well as MOF
      heterostructures on a given surface in a well-defined and oriented fashion. MOFs
      are solid-state materials typically formed by solvothermal reactions and their
      crystallization from the liquid phase involves the surface chemistry of their
      building blocks. This Review brings together various key aspects of the surface
      chemistry of MOFs.

PMID- 21190184
TI  - Functional characterization of a BRAF insertion mutant associated with pilocytic
      astrocytoma.
AB  - Pilocytic astrocytoma (PA) is emerging as a tumor entity with dysregulated
      Ras/Raf/MEK/ERK signaling. Common genetic lesions observed in PA, which are
      linked to aberrant ERK pathway activity, include either NF1 inactivation, KRAS or
      BRAF gain-of-function mutations. To investigate the mutation spectrum within the
      proto-oncogene encoding the Ser/Thr-kinase B-Raf in more detail, we analyzed 64
      primary tumor samples from children with PA including two patients with
      neurofibromatosis type 1 (NF1). The well-known BRAF(V600E)  mutation was found in
      6/64 (9.38%) of our samples. For the first time, we report concomitant presence
      of a somatic BRAF(V600E)  mutation in an NF1 patient indicating that more than
      one Ras/ERK pathway component can be affected in PA. Furthermore, 2/64 (3.13%) of
      our samples carried a 3-bp insertion in BRAF resulting in the duplication of
      threonine 599. This conserved residue is located within the activation segment
      and, if phosphorylated in a Ras-dependent manner, plays a key role in Raf
      activation. Here, we demonstrate that this mutant (B-Raf(insT) ) and another B
      Raf mutant, which carries two additional threonine residues at this position,
      display an in vitro kinase activity and cellular MEK/ERK activation potential
      comparable to those of B-Raf(V600E) . Notably, replacement of threonines by
      valine residues had similar effects on B-Raf activity, suggesting that the
      distortion of the peptide backbone by additional amino acids rather than the
      insertion of additional, potential phosphorylation sites destabilizes the
      inactive conformation of the kinase domain. We also demonstrate that B-Raf(insT) 
      and B-Raf(V600E) , but not B-Raf(wt) , provoke drastic morphological alterations
      in human astrocytes.

PMID- 21190185
TI  - Polymorphonuclear granulocytes in human head and neck cancer: enhanced
      inflammatory activity, modulation by cancer cells and expansion in advanced
      disease.
AB  - The progression of epithelial cancer is associated with an intense immunological
      interaction between the tumor cells and immune cells of the host. However, little
      is known about the interaction between tumor cells and polymorphonuclear
      granulocytes (PMNs) in patients with head and neck squamous cell carcinoma
      (HNSCC). In our study, we investigated systemic PMN-related alterations in HNSCC,
      the role of tumor-infiltrating PMNs and their modulation by the tumor
      microenvironment. We assessed the infiltration of HNSCC tissue by PMNs
      (retrospectively) and systemic PMN-related alterations in blood values
      (prospectively) in HNSCC patients (n = 99 and 114, respectively) and control
      subjects (n = 41). PMN recruitment, apoptosis and inflammatory activity were
      investigated in an in vitro system of peripheral blood PMNs and a human HNSCC
      cell line (FaDu). HNSCC tissue exhibited considerable infiltration by PMNs, and
      strong infiltration was associated with poorer survival in advanced disease. PMN
      count, neutrophil-to-lymphocyte ratio and serum concentrations of CXCL8
      (interleukin-8), CCL4 (MIP-1beta) and CCL5 (RANTES) were significantly higher in
      the peripheral blood of HNSCC patients than in that of controls. In vitro, HNSCC
      conditioned medium inhibited apoptosis of PMNs, increased chemokinesis and
      chemotaxis of PMNs, induced release of lactoferrin and matrix metalloproteinase 9
      by PMNs and enhanced the secretion of CCL4 by PMN. Our findings demonstrate
      alterations in PMN biology in HNSCC patients. In vitro, tumor-derived factors
      modulate cellular functions of PMNs and increase their inflammatory activity.
      Thus, the interaction between HNSCC and PMNs may contribute to host-mediated
      changes in the tumor microenvironment.

PMID- 21190186
TI  - ADAM15 to alpha5beta1 integrin switch in colon carcinoma cells: a late event in
      cancer progression associated with tumor dedifferentiation and poor prognosis.
AB  - ADAM15, a member of the A Disintegrin And Metalloproteinase (ADAM) family, is a
      membrane protein containing an adhesion domain that binds to alpha5beta1 integrin
      through a unique RGD domain. ADAM15, expressed by human normal colonocytes, is
      involved in epithelial wound healing and tissue remodeling in inflammatory bowel
      disease. The aims of our study were (i) to analyze ADAM15 expression in a series
      of colon carcinomas and paired normal mucosa and (ii) to integrate the spatial
      relationship of ADAM15 with its binding partners alpha5beta1 integrin, a
      mesenchymal marker, as well as with other adhesion molecules, alpha3beta1
      integrin and E-cadherin. A series of 94 colon carcinomas of the non other
      specified category were graded according to the World Health Organization
      classification. Immunohistochemistry was performed on frozen tissue sections
      using antibodies directed to ADAM15, alpha5beta1 and alpha3beta1 integrins, and E
      cadherin. ADAM15 was quantified at the mRNA level. Finally, promoter methylation
      of ADAM15 was examined as well as the microsatellite instability status
      (MSS/MSI). Thirty-six percent of colorectal carcinomas displayed a reduced
      expression of ADAM15 in cancer cells, confirmed at the mRNA level in most cases,
      without promoter methylation. ADAM15 down-regulation was associated with
      histologically poorly differentiated carcinomas. In addition, it was associated
      with the acquisition of alpha5beta1 by cancer cells and down-regulation of
      alpha3beta1 integrin and E-cadherin. Finally this profile that includes
      characteristic of epithelial to mesenchymal transition is a late progression
      event of colon cancer with a poor prognosis.

PMID- 21190187
TI  - Combined CADM1 and MAL promoter methylation analysis to detect (pre-)malignant
      cervical lesions in high-risk HPV-positive women.
AB  - Given the lower specificity for high-grade cervical lesions of high-risk human
      papillomavirus (hrHPV) testing compared to cytology, additional triage testing
      for hrHPV test-positive women is needed to detect high-grade cervical lesions.
      Here, we tested whether combined methylation analysis for cell adhesion molecule
      1 (CADM1) and T-lymphocyte maturation associated protein (MAL), both functionally
      involved in cervical carcinogenesis, could serve as such a triage marker. Four
      quantitative methylation-specific PCRs (qMSP), two for CADM1 (regions M12 and
      M18) and MAL (regions M1 and M2) each, were applied to 261 cervical tissue
      specimens ranging from no neoplasia to carcinoma. When qMSPs were combined and
      positivity for at least one of the qMSPs in the combination was taken into
      account, the highest positivity rates for cervical intraepithelial neoplasia
      grade 3 (CIN3) lesions (97%) and squamous cell- and adeno-carcinomas (99%) were
      obtained by combining a single CADM1 marker with a single MAL marker. Subsequent
      qMSP analysis of 70 GP5+/6+-PCR hrHPV-positive scrapings revealed that a two
      marker panel consisting of CADM1-M18 and MAL-M1 was most discriminative,
      detecting 90% of women with CIN3 (n = 30), whereas it showed a positive result in
      only 13.5% of women without cervical disease (n = 40). Finally, we applied hrHPV
      GP5+/6+-PCR testing followed by CADM1-M18/MAL-M1 methylation analysis to a cohort
      of 79 women visiting the outpatient colposcopy clinic. hrHPV testing revealed a
      sensitivity of 97% and a specificity of 33% for CIN3+. Additional CADM1-M18/MAL
      M1 methylation analysis on the hrHPV-positive women increased the specificity to
      78% with a sensitivity of 70%. In conclusion, the methylation marker panel CADM1
      M18 and MAL-M1 may serve as an alternative molecular triage tool for hrHPV
      positive women.

PMID- 21190188
TI  - HPV involvement in tonsillar cancer: prognostic significance and clinically
      relevant markers.
AB  - The association of high-risk human papillomaviruses (HR HPVs) with tonsillar
      cancer (TC) has been documented. Because patients with HPV-associated tumors show
      better survival rates, modification of their treatment regimen is being
      considered. It is therefore crucial to find markers for the identification of
      patients whose tumors are linked to viral infection. A cohort of 109 patients
      with primary TC was screened for HPV DNA presence in the tumor tissues and HPV
      specific antibodies in sera. Data regarding risk factors and clinical parameters
      were collected. Forty-five specimens were analyzed for the expression of viral E6
      and E2-region mRNA, and the p16 and p53 protein expression status was assessed by
      immunohistochemistry. The overall prevalence of HPV DNA in TC tissues was 65.1%.
      Ninety-three percent of HR HPV DNA-positive samples expressed E6*I mRNA. E2
      region mRNA expression was detected in 36% of positive samples, which implies
      that the virus is integrated in 64% of HPV DNA/RNA-positive tumors. p16
      overexpression and the presence of antibodies specific to HPV16 E6/E7
      oncoproteins correlated well with HPV DNA and RNA presence. The disease-specific
      survival rate of patients with HPV DNA-positive tumors was significantly higher
      than that of HPV DNA-negative patients. In addition to providing further evidence
      of the involvement of HPV infection in the etiopathogenesis of a proportion of TC
      cases, our study demonstrates that p16 immunostaining and anti-E6/E7 antibodies
      as surrogate markers of HPV involvement represent specific, sensitive and
      clinically accessible assays for the identification of TC patients who have a
      considerably better prognosis.

PMID- 21190189
TI  - HFE polymorphisms influence the response to chemotherapeutic agents via induction
      of p16INK4A.
AB  - HFE is a protein that impacts cellular iron uptake. HFE gene variants are
      identified as risk factors or modifiers for multiple diseases. Using HFE stably
      transfected human neuroblastoma cells, we found that cells carrying the C282Y HFE
      variant do not differentiate when exposed to retinoic acid. Therefore, we
      hypothesized HFE variants would impact response to therapeutic agents. Both the
      human neuroblastoma and glioma cells that express the C282Y HFE variant are
      resistant to Temodar, geldanamycin and gamma-radiation. A gene array analysis
      revealed that p16INK4A (p16) expression was increased in association with C282Y
      expression. Decreasing p16 protein by siRNA resulted in increased vulnerability
      to all of the therapeutic agents suggesting that p16 is responsible for the
      resistance. Decreasing HFE expression by siRNA resulted in a 85% decrease in p16
      expression in the neuroblastoma cells but not the astrocytoma cells. These data
      suggest a potential direct relationship between HFE and p16 that may be cell
      specific or mediated by different pathways in the different cell types. In
      conclusion, the C282Y HFE variant impacts the vulnerability of cancer cells to
      current treatment strategies apparently by increasing expression of p16. Although
      best known as a tumor suppressor, there are multiple reports that p16 is elevated
      in some forms of cancer. Given the frequency of the HFE gene variants, as high as
      10% of the Caucasian population, these data provide compelling evidence that the
      C282Y HFE variant should be part of a pharmacogenetic strategy for evaluating
      treatment efficacy in cancer cells.

PMID- 21190190
TI  - Long-term persistence of systemic and mucosal immune response to HPV-16/18 AS04
      adjuvanted vaccine in preteen/adolescent girls and young women.
AB  - Vaccination against oncogenic human papillomavirus (HPV) types is one key
      intervention for cervical cancer prevention. This follow-up study assessed the
      persistence of the systemic and mucosal immune responses together with the safety
      profile of the HPV-16/18 AS04-adjuvanted vaccine administered to young women aged
      10-25 years. Serum and cervicovaginal secretion (CVS) samples were collected at
      prespecified time-points during the 48-month follow-up period. Anti-HPV-16/18
      antibody levels in serum and CVS were measured by enzyme-linked immunosorbent
      assay (ELISA). At Month 48, all subjects remained seropositive for serum anti-HPV
      16 and -18 antibodies. As previously observed, anti-HPV-16 and -18 antibodies
      levels (ELISA Units/mL) were higher in subjects vaccinated at the age of 10-14
      years (2862.2 and 940.8) compared to subjects vaccinated at the age of 15-25
      years (1186.2 and 469.8). Moreover, anti-HPV-16 and -18 antibodies in CVS were
      still detectable for subjects aged 15-25 years (84.1% and 69.7%, respectively).
      There was a strong correlation between serum and CVS anti-HPV-16 and -18
      antibodies levels (correlation coefficients = 0.84 and 0.90 at Month 48,
      respectively) supporting the hypothesis of transudation or exudation of serum
      immunoglobulin G antibodies through the cervical epithelium. The HPV-16/18 AS04
      adjuvanted vaccine had a clinically acceptable safety profile. In conclusion,
      this follow-up study shows that the HPV-16/18 AS04-adjuvanted vaccine
      administered to preteen/adolescents girls and young women induces long-term
      systemic and mucosal immune response and has a clinically acceptable safety
      profile up to 4 years after the first vaccine dose.

PMID- 21190191
TI  - Alcohol drinking and esophageal squamous cell carcinoma with focus on light
      drinkers and never-smokers: a systematic review and meta-analysis.
AB  - Quantification of the association between alcohol drinking and risk of esophageal
      squamous cell carcinoma (ESCC) is an open issue, particularly among light alcohol
      drinkers, never-smokers, and Asian populations, in which some high-risk
      polymorphisms in alcohol metabolizing genes are more prevalent. To address these
      issues, we conducted a systematic review and meta-analysis using 40 case-control
      and 13 cohort studies that reported on the risk associated with alcohol drinking
      for at least three levels of consumption. In studies adjusted for age, sex, and
      tobacco smoking, the relative risk (RR) and 95% confidence interval (CI) for the
      association between light alcohol drinking (<= 12.5 g/d) and risk of ESCC was
      1.38 (1.14-1.67). The association was slightly stronger in Asian countries than
      in other populations. The adjusted RRs (95% CIs) were 2.62 (2.07-3.31) for
      moderate drinking (>12.5-<50 g/d) and 5.54 (3.92-7.28) for high alcohol intake
      (>=50 g/d); the RRs were slightly higher in non-Asian populations. In prospective
      studies, the RR (95% CI) was 1.35 (0.92-1.98) for light, 2.15 (1.55-2.98) for
      moderate, and 3.35 (2.06-5.46) for high alcohol intakes; light drinking showed an
      association with ESCC in Asia (five studies) but not in other regions (three
      studies). Among never-smokers (nine studies), the RR (95% CI) was 0.74 (0.47
      1.16) for light, 1.54 (1.09-2.17) for moderate, and 3.09 (1.75-5.46) for high
      intakes. This meta-analysis further corroborates the association of moderate and
      high alcohol intake with risk of ESCC and provides risk estimates based on
      multiple prospective studies. Light alcohol intake appears to be associated to
      ESCC mainly in studies in Asia, which suggests a possible role of genetic
      susceptibility factors.

PMID- 21190192
TI  - Screening detected prostate cancers in type 2 diabetics.

PMID- 21190193
TI  - Effects of antihistamine and anti-inflammatory medication use on risk of specific
      glioma histologies.
AB  - Several studies have shown a decrease in glioma risk associated with a personal
      history of allergic conditions and the medications used to treat the symptoms.
      However, few studies have been able to examine risk within histological subgroups
      of glioma. Case-control data from M. D. Anderson Cancer Center and University of
      California, San Francisco were pooled to conduct the analysis stratified by
      histological subtype. A risk prediction model considering inflammation-related
      variables and antihistamine use was built using logistic regression. Of the
      subtypes examined, long-term antihistamine use was associated with increased risk
      of anaplastic gliomas, especially when length of use was considered in
      conjunction with history of asthma or allergy. Anaplastic cases with no history
      of asthma or allergy were 2.94 times more likely than controls to report
      antihistamine use for 10 years or more; whereas anaplastic cases with a history
      of asthma or allergy were 2.34 times more likely than controls to report
      antihistamine use for 10 years or more. Furthermore, anti-inflammatory medication
      use was associated with a protective effect against glioblastoma (OR = 0.80; 95%
      CI: 0.65, 0.99), especially among individuals with no history of asthma or
      allergies. No statistically significant effects of anti-inflammatory drugs or
      antihistamines were evident for the other histological subtypes. Thus, modulation
      of the immune system by the use of common drugs, such as antihistamines or
      nonsteroidal anti-inflammatory drugs, may contribute to the development of
      certain types of brain tumors.

PMID- 21190195
TI  - Salivary metabolite signatures of oral cancer and leukoplakia.
AB  - Oral cancer, one of the six most common human cancers with an overall 5-year
      survival rate of <50%, is often not diagnosed until it has reached an advanced
      stage. The aim of the current study is to explore salivary metabolomics as a
      disease diagnostic and stratification tool for oral cancer and leukoplakia and
      evaluate the potential of salivary metabolome for detection of oral squamous cell
      carcinoma (OSCC). Saliva metabolite profiling for a group of 37 OSCC patients, 32
      oral leukoplakia (OLK) patients and 34 healthy subjects was performed using
      ultraperformance liquid chromatography coupled with quadrupole/time-of-flight
      mass spectrometry in conjunction with multivariate statistical analysis. The
      OSCC, OLK and healthy control groups demonstrate characteristic salivary
      metabolic signatures. A panel of five salivary metabolites including gamma
      aminobutyric acid, phenylalanine, valine, n-eicosanoic acid and lactic acid were
      selected using OPLS-DA model with S-plot. The predictive power of each of the
      five salivary metabolites was evaluated by receiver operating characteristic
      curves for OSCC. Valine, lactic acid and phenylalanine in combination yielded
      satisfactory accuracy (0.89, 0.97), sensitivity (86.5% and 94.6%), specificity
      (82.4% and 84.4%) and positive predictive value (81.6% and 87.5%) in
      distinguishing OSCC from the controls or OLK, respectively. The utility of
      salivary metabolome diagnostics for oral cancer is successfully demonstrated in
      this study and these results suggest that metabolomics approach complements the
      clinical detection of OSCC and stratifies the two types of lesions, leading to an
      improved disease diagnosis and prognosis.

PMID- 21190218
TI  - Differential long-term depression in CA3 but not in dentate gyrus following low
      frequency stimulation of the medial perforant path.
AB  - Synaptic plasticity may depend not only on the afferent fibers but also on the
      recipient structure. The medial perforant path (MPP) from the entorhinalcortex
      projects to both the dentate gyrus (DG) and CA3, resulting in excitatory
      postsynaptic potentials (EPSPs) in both areas. In this study, we showed that long
      term depression (LTD) following low-frequency stimulation of MPP was found only
      in CA3a, a CA3 subfield, but not in DG. Field potentials were recorded and
      current source density (CSD) analyzed in CA3a and DG following stimulation of MPP
      in urethane-anesthetized rats. MPP evoked a short-latency population spike (PS)
      and EPSP in CA3a, <2.5 ms delayed from the respective events in DG. A small
      electrolytic lesion of CA3a abolished the locally recorded PS in CA3a but did not
      affect the responses in the DG. Low-frequency stimulation of the MPP for 600
      pulses at 5 Hz, but not at 1 Hz, resulted in LTD of up to 2 h in CA3a but not in
      DG. High-frequency stimulation (400 Hz bursts) of the MPP resulted in long-term
      potentiation (LTP) in both CA3a and DG. LTD at CA3a was blocked by a prior
      intracerebroventricular administration of an N-methyl-D-aspartate receptor
      (NMDAR) antagonist DL-2-amino-5-phosphonovaleric acid or a nonselective group
      I/II metabotropic glutamate receptor (mGluR) antagonist (RS)-alpha-methyl-4
      carboxyphenylglycine. We conclude that an NMDAR and mGluR sensitive LTD is
      induced in CA3 but not in the DG following low-frequency MPP stimulation in vivo,
      and the bi-directional synaptic plasticity in CA3 may be responsible for its
      behavioral functions.

PMID- 21190217
TI  - Methamphetamine treatment during development attenuates the dopaminergic deficits
      caused by subsequent high-dose methamphetamine administration.
AB  - Administration of high doses of methamphetamine (METH) causes persistent
      dopaminergic deficits in both nonhuman preclinical models and METH-dependent
      persons. Noteworthy, adolescent [i.e., postnatal day (PND) 40] rats are less
      susceptible to this damage than young adult (PND90) rats. In addition, biweekly
      treatment with METH, beginning at PND40 and continuing throughout development,
      prevents the persistent dopaminergic deficits caused by a "challenge" high-dose
      METH regimen when administered at PND90. Mechanisms underlying this "resistance"
      were thus investigated. Results revealed that biweekly METH treatment throughout
      development attenuated both the acute and persistent deficits in VMAT2 function,
      as well as the acute hyperthermia, caused by a challenge METH treatment.
      Pharmacokinetic alterations did not appear to contribute to the protection
      afforded by the biweekly treatment. Maintenance of METH-induced hyperthermia
      abolished the protection against both the acute and persistent VMAT2-associated
      deficits suggesting that alterations in thermoregulation were caused by exposure
      of rats to METH during development. These findings suggest METH during
      development prevents METH-induced hyperthermia and the consequent METH-related
      neurotoxicity.

PMID- 21190219
TI  - Chronic corticosterone exposure alters postsynaptic protein levels of PSD-95,
      NR1, and synaptopodin in the mouse brain.
AB  - Animal models provide compelling evidence that chronic stress is associated with
      biochemical and morphological changes in the brain, many of which are mediated by
      corticosterone, a principal glucocorticoid synthesized in the rodent adrenal
      cortex and secreted in response to stress. To better characterize the effects of
      chronic corticosterone at the synaptic and subsynaptic level, we implanted three
      month-old male C57B/6 mice with 2 * 5 mg corticosterone pellets (CORT group, n =
      14), 21 day release formulation (20 mg/kg/day dose) or placebo pellets (Placebo
      group, n = 14), 21-day release formulation. After 20 days, brains were removed.
      One hemisphere was frozen for biochemical analysis by synaptosomal fractionation
      with Western blotting, and the other hemisphere was fixed for
      immunohistochemistry. Localization and expression levels for PSD-95, NR1, and
      synaptopodin proteins were assessed. Biochemical analysis revealed lower protein
      levels of PSD-95 (32% decrease, P < 0.001), NR1 (47%, P = 0.01), and synaptopodin
      (65%, P < 0.001) in the postsynaptic density subsynaptic fraction of the CORT
      group. Optical densitometry in immunohistochemically labeled sections also found
      lower levels of PSD-95 in synaptic fields of the dentate gyrus (PSD-95, 33%
      decrease, P < 0.001; NR1, 31%, P < 0.001; synaptopodin, 40%, P < 0.001) and the
      CA3 stratum lucidum (36%, P < 0.001, 40%, P < 0.001, and 35%, P < 0.001) of the
      CORT group. While mechanistic relationships for these changes are not yet known,
      we speculate that synaptopodin, which is involved in regulation of spine calcium
      kinetics and posttranslational modification and transport of locally synthesized
      proteins, may play an important role in the changes of PSD-95 and NR1 protein
      levels and other synaptic alterations.

PMID- 21190220
TI  - Sensitivity of kinetic macro parameters to changes in dopamine synthesis,
      storage, and metabolism: a simulation study for [18F]FDOPA PET by a model with
      detailed dopamine pathway.
AB  - Quantitative interpretation of brain [18F]FDOPA PET data has been made possible
      by several kinetic modeling approaches, which are based on different assumptions
      about complex [18F]FDOPA metabolic pathways in brain tissue. Simple kinetic macro
      parameters are often utilized to quantitatively evaluate metabolic and
      physiological processes of interest, which may include DDC activity, vesicular
      storage, and catabolism from (18) F-labeled dopamine to DOPAC and HVA. A macro
      parameter most sensitive to the changes of these processes would be potentially
      beneficial to identify impaired processes in a neurodegenerative disorder such as
      Parkinson's disease. The purpose of this study is a systematic comparison of
      several [18F]FDOPA macro parameters in terms of sensitivities to process-specific
      changes in simulated time-activity curve (TAC) data of [18F]FDOPA PET. We
      introduced a multiple-compartment kinetic model to simulate PET TACs with
      physiological changes in the dopamine pathway. TACs in the alteration of dopamine
      synthesis, storage, and metabolism were simulated with a plasma input function
      obtained by a non-human primate [18F]FDOPA PET study. Kinetic macro parameters
      were calculated using three conventional linear approaches (Gjedde-Patlak, Logan,
      and Kumakura methods). For simulated changes in dopamine storage and metabolism,
      the slow clearance rate (k(loss) ) as calculated by the Kumakura method showed
      the highest sensitivity to these changes. Although k(loss) performed well at
      typical ROI noise levels, there was large bias at high noise level. In contrast,
      for simulated changes in DDC activity it was found that K(i) and V(T), estimated
      by Gjedde-Patlak and Logan method respectively, have better performance than
      k(loss).

PMID- 21190246
TI  - Nanogel-based scaffold delivery of prostaglandin E(2) receptor-specific agonist
      in combination with a low dose of growth factor heals critical-size bone defects
      in mice.
AB  - OBJECTIVE: Regeneration of bone requires the combination of appropriate drugs and
      an appropriate delivery system to control cell behavior. However, the delivery of
      multiple drugs to heal bone is complicated by the availability of carriers. The
      aim of this study was to explore a new system for delivery of a selective EP4
      receptor agonist (EP4A) in combination with low-dose bone morphogenetic protein 2
      (BMP-2). METHODS: Combined delivery of EP4A and BMP-2 was carried out with a
      nanogel-based scaffold in the shape of a disc, to repair critical-size circle
      shaped bone defects in calvariae that otherwise did not heal spontaneously.
      RESULTS: Combination treatment with EP4A and low-dose BMP-2 in nanogel
      efficiently activated bone cells to regenerate calvarial bone by forming both
      outer and inner cortical plates as well as bone marrow tissue to regenerate a
      structure similar to that of intact calvaria. EP4A enhanced low-dose BMP-2
      induced cell differentiation and activation of transcription events in
      osteoblasts. CONCLUSION: These data indicate that combined delivery of EP4A and
      low-dose BMP-2 via nanogel-based hydrogel provides a new system for bone repair.

PMID- 21190259
TI  - Enhancement in MALDI-TOF MS analysis of the low molecular weight human serum
      proteome.

PMID- 21190266
TI  - Ion-exchange resins greatly facilitate refolding of like-charged proteins at high
      concentrations.
AB  - Protein refolding is a crucial step for the production of therapeutic proteins
      expressed in bacteria as inclusion bodies. In vitro protein refolding is severely
      impeded by the aggregation of folding intermediates during the folding process,
      so inhibition of the aggregation is the most effective approach to high
      efficiency protein refolding. We have herein found that electrostatic repulsion
      between like-charged protein and ion exchange gel beads can greatly suppress the
      aggregation of folding intermediates, leading to the significant increase of
      native protein recovery. This finding is extensively demonstrated with three
      different proteins and four kinds of ion-exchange resins when the protein and ion
      exchange gel are either positively or negatively charged at the refolding
      conditions. It is remarkable that the enhancing effect is significant at very
      high protein concentrations, such as 4 mg/mL lysozyme (positively charged) and 2
      mg/mL bovine serum albumin (negatively charged). Moreover, the folding kinetics
      is not compromised by the presence of the resins, so fast protein refolding is
      realized at high protein concentrations. It was not realistic by any other
      approaches. The working mechanism of the like-charged resin is considered due to
      the charge repulsion that could induce oriented alignment of protein molecules
      near the charged surface, leading to the inhibition of protein aggregation. The
      molecular crowding effect induced by the charge repulsion may also contribute to
      accelerating protein folding. The refolding method with like-charged ion
      exchangers is simple to perform, and the key material is easy to separate for
      recycling. Moreover, because ion exchangers can work as adsorbents of oppositely
      charged impurities, an operation of simultaneous protein refolding and
      purification is possible. All the characters are desirable for preparative
      refolding of therapeutic proteins expressed in bacteria as inclusion bodies.

PMID- 21190261
TI  - Rapid monitoring of iron-chelating therapy in thalassemia major by a new
      cardiovascular MR measure: the reduced transverse relaxation rate.
AB  - In iron overload, almost all the excess iron is stored intracellularly as rapidly
      mobilizable ferritin iron and slowly exchangeable hemosiderin iron. Increases in
      cytosolic iron may produce oxidative damage that ultimately results in
      cardiomyocyte dysfunction. Because intracellular ferritin iron is evidently in
      equilibrium with the low-molecular-weight cytosolic iron pool, measurements of
      ferritin iron potentially provide a clinically useful indicator of changes in
      cytosolic iron. The cardiovascular magnetic resonance (CMR) index of cardiac iron
      used clinically, the effective transverse relaxation rate (R(2)*), is principally
      influenced by hemosiderin iron and changes only slowly over several months, even
      with intensive iron-chelating therapy. Another conventional CMR index of cardiac
      iron, the transverse relaxation rate (R(2)), is sensitive to both hemosiderin
      iron and ferritin iron. We have developed a new MRI measure, the 'reduced
      transverse relaxation rate' (RR(2)), and have proposed in previous studies that
      this measure is primarily sensitive to ferritin iron and largely independent of
      hemosiderin iron in phantoms mimicking ferritin iron and human liver explants. We
      hypothesized that RR(2) could detect changes produced by 1 week of iron-chelating
      therapy in patients with transfusion-dependent thalassemia. We imaged 10 patients
      with thalassemia major at 1.5 T in mid-ventricular short-axis planes of the
      heart, initially after suspending iron-chelating therapy for 1 week and
      subsequently after resuming oral deferasirox. After resuming iron-chelating
      therapy, significant decreases were observed in the mean myocardial RR(2) (7.8%,
      p < 0.01) and R(2) (5.5%, p < 0.05), but not in R(2)* (1.7%, p > 0.90). Although
      the difference between changes in RR(2) and R(2) was not significant (p > 0.3),
      RR(2) was consistently more sensitive than R(2) (and R(2)*) to the resumption of
      iron-chelating therapy, as judged by the effect sizes of relaxation rate
      differences detected. Although further studies are needed, myocardial RR(2) may
      be a promising investigational method for the rapid assessment of the effects of
      iron-chelating therapy in the heart.

PMID- 21190268
TI  - Design and characterization of a polymeric MRI contrast agent based on PVA for in
      vivo living-cell tracking.
AB  - A novel water-soluble MRI contrast agent for in vivo living cell tracking was
      developed. Unlike the conventional in vivo cell tracking system based on
      superparamagnetic iron oxide beads, the newly developed contrast agent is
      eliminated from the body when the contrast agent exits the cells upon cell death,
      which makes living cell tracking possible. The contrast agent is composed of
      gadolinium chelates (Gd-DOTA) and a water-soluble carrier, poly(vinyl alcohol)
      (PVA), which is known to interact with cells and tissues very weakly. Since the
      Gd-PVA was not taken up by cells spontaneously, the electroporation method was
      used for cell labeling. The delivered Gd-PVA was localized only in the cytosolic
      compartment of growing cells with low cytotoxicity and did not leak out of the
      living cells for long periods of time. This stability may be due to the weak cell
      membrane affinity of Gd-PVA, and did not affect cell proliferation at all. After
      cell labeling, signal enhancement of cells was observed in vitro and in vivo.
      These results indicate that Gd-PVA can visualize only the living cells in vivo
      for a long period of time, even in areas deep within large animal bodies.

PMID- 21190269
TI  - NMR relaxation and magnetic properties of superparamagnetic nanoworms.
AB  - Maghemite particles are used as T2 contrast agents for magnetic resonance
      imaging, especially for molecular and cellular imaging. Linear clusters of
      particles - called nanoworms - were recently developed to enhance the targeting
      efficiency. In this work, the magnetic and NMR relaxation properties of these
      nanoworms are studied at multiple magnetic fields. After the usual saturation at
      0.5 T, the magnetization of the worms is still increasing, which results in an
      appreciable increase of the transverse relaxivity at high magnetic fields. The
      obtained relaxivities are typical of superparamagnetic particles of iron oxide
      (SPIOs). The transverse relaxation of the worms is clearly more efficient than
      for the isolated grains, which is confirmed by computer simulations. At high
      field, the longitudinal relaxation of the worms is less pronounced than for the
      grains, as expected for SPIOs. The nanoworms thus constitute a promising T2 agent
      for cellular and molecular imaging.

PMID- 21190270
TI  - Liver volume in trisomy 21 and euploid fetuses at 11 to 13 weeks.
AB  - OBJECTIVES: To compare liver volume between trisomy 21 and euploid fetuses at 11
      to 13 weeks' gestation. METHODS: Fetal liver volume was measured by 3D ultrasound
      in fetuses at low risk of aneuploidies (n = 200) and another group at high risk,
      including 148 euploid and 37 with trisomy 21. The association of liver volume
      with fetal nuchal translucency (NT) thickness, tricuspid regurgitation and
      reversed a-wave in the ductus venosus was investigated. RESULTS: In the low-risk
      group, fetal liver volume increased exponentially with fetal crown-rump length
      (CRL) from a median of 0.5 cm(3) at CRL of 45 mm to about 2.5 cm(3) at CRL of 84
      mm. In 27 (73.0%) of the trisomy 21 fetuses liver volume was above the 95th
      percentile of the low-risk group, whereas in the euploid fetuses liver volume was
      not significantly altered (P = 0.521). There were no significant contributions to
      liver volume from fetal NT (P = 0.508), tricuspid regurgitation (P = 0.958) or
      reversed a-wave in the ductus venosus (P = 0.872). CONCLUSION: In trisomy 21
      fetuses at 11 to 13 weeks liver volume is increased.

PMID- 21190290
TI  - A role for human neuroglobin in apoptosis.
AB  - Over the past decade, following the discovery of the human heme protein
      neuroglobin, many studies have searched for evidence for this protein's mechanism
      of action. Much data has accrued showing that high levels of neuroglobin will
      protect cells from apoptotic cell death, following a wide range of challenges.
      Various explanations of its actions, based on measured reactivity with oxygen,
      nitric oxide, or free radicals, have been proposed, but none have, as yet, been
      substantiated in vivo. Following preliminary experiments, it was previously
      hypothesised that "the central role of neuroglobin in highly metabolically active
      cells and retinal and brain neurons is to reset the trigger level of
      mitochondrial cytochrome c release necessary to commit the cells to apoptosis"
      (I.U.M.B.M. Life (2008) 60, 398). In this article, we review the evidence, which
      has accumulated to support this hypothesised mechanism of action of neuroglobin
      and integrate this data, with other reported intracellular functions of
      neuroglobin, to suggest a plausible central role for neuroglobin in the control
      of apoptosis.

PMID- 21190291
TI  - KLF1 directly coordinates almost all aspects of terminal erythroid
      differentiation.
AB  - The molecular events and transcriptional mechanisms that underlie erythropoiesis
      are of great interest to biologists and hematologists since disorders of
      erythrocytes are common and remain relatively poorly understood. Kruppel-like
      factor 1 (KLF1) is a critical transcription factor for erythropoiesis in mice and
      man. Recently the use of chromatin immunoprecipitation (ChIP) coupled to next
      generation DNA sequencing (ChIP-seq) has led to an updated understanding of how
      KLF1 functions in vivo. The full extent of KLF1 target genes have provided new
      insights into erythropoiesis, and have established that KLF1 controls almost all
      aspects of erythroid cell development and maturation.

PMID- 21190292
TI  - Naturally occurring organic osmolytes: from cell physiology to disease
      prevention.
AB  - Osmolytes are naturally occurring organic compounds, which represent different
      chemical classes including amino acids, methylamines, and polyols. By
      accumulating high concentrations of osmolytes, organisms adapt to perturbations
      that can cause structural changes in their cellular proteins. Osmolytes shift
      equilibrium toward natively-folded conformations by raising the free energy of
      the unfolded state. As osmolytes predominantly affect the protein backbone, the
      balance between osmolyte-backbone interactions and amino acid side chain-solvent
      interactions determines protein folding. Abnormal cell volume regulation
      significantly contributes to the pathophysiology of several disorders, and cells
      respond to these changes by importing, exporting, or synthesizing osmolytes to
      maintain volume homeostasis. In recent years, it has become quite evident that
      cells regulate many biological processes such as protein folding, protein
      disaggregation, and protein-protein interactions via accumulation of specific
      osmolytes. Many genetic diseases are attributed to the problems associated with
      protein misfolding/aggregation, and it has been shown that certain osmolytes can
      protect these proteins from misfolding. Thus, osmolytes can be utilized as
      therapeutic targets for such diseases. In this review article, we discuss the
      role of naturally occurring osmolytes in protein stability, underlying
      mechanisms, and their potential use as therapeutic molecules.

PMID- 21190293
TI  - Biochemical studies on Helicobacter pylori arginase: insight into the difference
      in activity compared to other arginases.
AB  - Arginase is a binuclear Mn(2+)-metalloenzyme of urea cycle that catalyzes the
      conversion of L-arginine to L-ornithine and urea. Unlike other arginases, the
      Helicobacter pylori enzyme is selective for Co(2+), and has lower catalytic
      activity. To understand the differences in the biochemical properties as well as
      activity compared to other arginases, we carried out a detailed investigation of
      different metal reconstituted H. pylori arginases that includes steady-state
      kinetics, fluorescence measurement, pH-dependent and oligomerization assays.
      Unlike other arginases (except human at physiological pH), the Co(2+)- and Mn(2+)
      reconstituted H. pylori enzymes exhibit cooperative mechanism of arginine
      hydrolysis, and undergo self-association and activation with increasing
      concentrations. Analytical gel-filtration assays in conjunction with the kinetic
      data showed that the protein exists as a mixture of monomer and dimer with
      monomer being the major form (other arginases exclusively exist as a trimer or
      hexamer) but the dimer is associated with higher catalytic activity. The
      proportion of dimer is found to decrease with increasing salt concentrations
      indicating that salt bridges play important roles in dimerization of the protein.
      Furthermore, the fluorescence measurement showed that Co(2+) ions play an
      important role in the local tertiary structure of the protein than Mn(2+). This
      is consistent with the pH-dependent studies where the Co(2+)-enzyme showed a
      single ionization compared to the double in the Mn(2+)-enzyme. Thus, this study
      presents the detailed biochemical and spectroscopic investigations into the
      differences in the biochemical properties and activity between H. pylori and
      other arginases.

PMID- 21190294
TI  - Numerical methods and computing in laboratories: from log tables and slide rules
      to laptop computers during a lifetime.

PMID- 21190297
TI  - Heparin exerts a dual effect on murine lupus nephritis by enhancing enzymatic
      chromatin degradation and preventing chromatin binding in glomerular membranes.
AB  - OBJECTIVE: Association of nucleosome-IgG immune complexes with glomerular
      basement membranes (GBMs) is an important event in the development of lupus
      nephritis. Preventing this binding and/or increasing nuclease sensitivity of
      nucleosomes may be viable strategies for the prevention of the disease.
      Theoretically, heparin may alter nucleosomal structure and increase sensitivity
      to proteinases and nucleases, and may also inhibit binding of nucleosomes and
      nucleosome-IgG complexes to basement membrane structures. The aim of this study
      was to investigate whether and eventually how heparin prevents murine lupus
      nephritis. METHODS: Surface plasmon resonance was used to analyze if heparin
      inhibits binding of nucleosomes to laminin and collagen. The effect of heparin on
      nuclease- and proteinase-mediated degradation of nucleosomes was analyzed by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis and agarose gel
      electrophoresis. In vitro results were compared with analyses in vivo in heparin
      treated (NZB * NZW)F(1) mice. Anti-double-stranded DNA antibody production,
      deposition of nucleosome-IgG complexes in GBMs, and development of proteinuria
      were monitored, and circulating chromatin fragments were quantified using
      quantitative polymerase chain reaction. RESULTS: In vitro studies demonstrated
      that heparin increased enzymatic degradation of nucleosomes and almost completely
      inhibited binding of nucleosomes to laminin and collagen. (NZB * NZW)F(1) mice
      treated with heparin demonstrated delayed or no antibody production and higher
      variation of circulating chromatin levels compared with untreated control mice.
      This effect was accompanied by highly reduced nucleosome-IgG complexes in GBMs
      and delayed development of nephritis. CONCLUSION: Increasing the degradation of
      nucleosomes, reducing their immunogenicity, and preventing binding of nucleosome
      IgG complexes in glomeruli together provide an alternative basis for the
      treatment of lupus nephritis.

PMID- 21190299
TI  - Toll-like receptor 2 induces Th17 myeloperoxidase autoimmunity while Toll-like
      receptor 9 drives Th1 autoimmunity in murine vasculitis.
AB  - OBJECTIVE: Autoantibodies constitute the hallmark of antineutrophil cytoplasmic
      antibody-associated vasculitis (AAV); however, CD4+ T cells play an essential
      role in the development of autoimmunity. Infection is associated with vasculitis,
      with Toll-like receptors (TLRs) a potential link between infection and
      autoimmunity. This study was undertaken to investigate the role of TLR ligation
      on cellular and humoral autoimmunity and glomerular injury in experimental
      myeloperoxidase (MPO)-induced AAV. METHODS: We analyzed autoimmune responses in
      wild-type mice immunized with MPO alone or coimmunized with MPO and a TLR-2 or
      TLR-9 ligand. The major vascular injury found in human disease,
      glomerulonephritis with focal necrosis, was triggered by administering a
      subnephritogenic dose of nephrotoxic serum. RESULTS: MPO alone induced low-titer
      antineutrophil cytoplasmic antibodies (ANCAs) without delayed-type
      hypersensitivity or CD4 cytokine responses. However, when MPO was given with
      either TLR ligand, cellular and humoral autoimmunity was enhanced, but with
      distinctly different CD4 subsets and IgG ANCA isotypes. TLR-2 ligand induced Th17
      autoimmunity, with retinoic acid receptor-related orphan nuclear receptor gammat
      dependent interleukin-17A (IL-17A) production. TLR-9 ligand promoted Th1
      autoimmunity, with enhanced production of interferon-gamma (IFNgamma) and Th1
      associated IgG subclasses. Glomerular vasculitis developed only after the
      administration of nephrotoxic serum in mice immunized with either TLR ligand and
      MPO. Glomerulonephritis directed by MPO and TLR-2 ligation was attenuated when IL
      17A was neutralized, while glomerulonephritis induced by MPO and TLR-9 ligation
      was attenuated when IFNgamma was neutralized. CONCLUSION: Our findings indicate a
      pathogenic role of TLRs in initiating autoimmune AAV. TLR-2 induces Th17 CD4
      cells while TLR-9 can also direct vasculitis, by directing Th1 autoimmunity.

PMID- 21190302
TI  - The prostaglandin E(2) system: a toolbox for skeletal repair?

PMID- 21190319
TI  - Alkyl 4-chlorobenzoyloxycarbamates as highly effective nitrogen source reagents
      for the base-free, intermolecular aminohydroxylation reaction.
AB  - Ethyl- (7), benzyl- (8), tert-butyl- (9), and fluorenylmethyl-4
      chlorobenzoyloxycarbamates (10) have been prepared as storable and easy-to
      prepare nitrogen sources for use in the intermolecular Sharpless
      aminohydroxylation reaction and its asymmetric variant. These reagents were found
      to be effective under base-free reaction conditions. The scope and limitations of
      these methods have been explored using a variety of alkenes, among which, trans
      cinnamates, in particular, proved to be good substrates.

PMID- 21190320
TI  - Spin component scaling in multiconfiguration perturbation theory.
AB  - We investigate a term-by-term scaling of the second-order energy correction
      obtained by perturbation theory (PT) starting from a multiconfiguration wave
      function. The total second-order correction is decomposed into several terms,
      based on the level and the spin pattern of the excitations. To define individual
      terms, we extend the same spin/different spin categorization of spin component
      scaling in various ways. When needed, identification of the excitation level is
      facilitated by the pivot determinant underlying the multiconfiguration PT
      framework. Scaling factors are determined from the stationary condition of the
      total energy calculated up to order 3. The decomposition schemes are tested
      numerically on the example of bond dissociation profiles and energy differences.
      We conclude that Grimme's parameters determined for single-reference Moller
      Plesset theory may give a modest error reduction along the entire potential
      surface, if adopting a multireference based PT formulation. Scaling factors
      obtained from the stationary condition show relatively large variation with
      molecular geometry, at the same time they are more efficient in reducing the
      error when following a bond dissociation process.

PMID- 21190322
TI  - Dynamics of uracil and 5-fluorouracil in DNA.
AB  - The prodrug 5-fluorouracil (5-FU), after activation into 5-F-dUMP, is an
      extensively used anticancer agent that inhibits thymidylate synthase and leads to
      increases in dUTP and 5-F-dUTP levels in cells. One mechanism for 5-FU action
      involves DNA polymerase mediated incorporation of dUTP and 5-F-dUTP into genomic
      DNA leading to U/A, 5-FU/A, or 5-FU/G base pairs. These uracil-containing lesions
      are recognized and excised by several human uracil excision repair glycosylases
      (hUNG2, hSMUG2, and hTDG) leading to toxic abasic sites in DNA that may
      precipitate cell death. Each of these enzymes uses an extrahelical base
      recognition mechanism, and previous studies with UNG have shown that extrahelical
      recognition is facilitated by destabilized base pairs possessing kinetically
      enhanced base pair opening rates. Thus, the dynamic properties of base pairs
      containing 5-FU and U are an important unknown in understanding the role of these
      enzymes in damage recognition and prodrug activation. The pH dependence of the
      (19)F NMR chemical shift of 5-FU imbedded in a model trinucleotide was used to
      obtain a pK(a) = 8.1 for its imino proton (10  degrees C). This is about 1.5
      units lower than the imino protons of uracil or thymine and indicates that at
      neutral pH 5-FU exists significantly as an ionized tautomer that can mispair with
      guanine during DNA replication. NMR imino proton exchange measurements show that
      U/A and 5-FU/A base pairs open with rate constants (k(op)) that are 6- and 13
      fold faster than a T/A base pair in the same sequence context. In contrast, these
      same base pairs have apparent opening equilibrium constants (alphaK(op)) that
      differ by less than a factor of 2, indicating that the closing rates (k(cl)) are
      enhanced by nearly equal amounts as k(op). These dynamic measurements are
      consistent with the previously proposed kinetic trapping model for extrahelical
      recognition by UNG. In this model, the enhanced intrinsic opening rates of
      destabilized base pairs allow the bound glycosylase to sample dynamic
      extrahelical excursions of thymidine and uracil bases as the first step in
      recognition.

PMID- 21190323
TI  - Synthesis of C1-symmetric chiral secondary diamines and their applications in the
      asymmetric copper(II)-catalyzed Henry (nitroaldol) reactions.
AB  - A small library of C(1)-symmetric chiral diamines (L1-L9) was constructed via
      condensing exo-(-)-bornylamine or (+)-(1S,2S,5R)-menthylamine with various Cbz
      protected amino acids. Among them, ligand L1/CuCl(2).2H(2)O complex (2.5 mol %)
      shows outstanding catalytic efficiency for Henry reaction between a variety of
      aldehydes and nitroalkanes to afford the expected products in high yields (up to
      98%) with excellent enantioselectivities (up to 99%) and moderate to good
      diastereoselectivities (up to 90:10). This process is air- and moisture tolerant
      and has been applied to the synthesis of (S)-2-amino-1-(3,4
      dimethoxyphenyl)ethanol (9), a key intermediate for (S)-epinephrine and (S)
      norepinephrine. On the basis of HRMS and X-ray diffraction analysis of the
      L1/CuCl(2) complex, a transition-state model was proposed to explain the origin
      of asymmetric induction. The low catalyst loading, excellent yields and
      enantioselectivities, inexpensive copper salt, and mild reaction conditions make
      our catalytic system to be practically useful.

PMID- 21190324
TI  - OH radical scavenging activity of Edaravone: mechanism and kinetics.
AB  - The reactions of OH radicals with the neutral and anionic forms of Edaravone (3
      methyl-1-phenyl-2-pyrazolin-5-one, EDA) have been studied using Density
      Functional Theory. Different mechanisms and reaction sites have been considered.
      The overall rate constant was found to be diffusion-limited (1.35 * 10(10) M(-1)
      s(-1), in aqueous solution), and in excellent agreement with the experimental
      results. Therefore, the present work supports previous evidence that EDA is an
      excellent (*)OH scavenger. The anionic form of EDA is predicted to react 8.6
      times faster than its neutral form. The preponderant mechanism was found to be
      different depending on the form of EDA reacting with the radical. For the anionic
      form, the single electron transfer mechanism was found to be the one contributing
      the most to the overall reactivity toward (*)OH (~ 44%), closely followed by
      radical adduct formation (~40%). For the neutral form, the latter was found to be
      the main mechanism, with contributions larger than 98%, regardless of the
      polarity of the environment. For the global reactivity of EDA toward OH radicals,
      at physiological pH, the main mechanism of reaction is proposed to be the
      sequential electron proton transfer. A detailed analysis of the UV-vis spectra is
      also provided. The excellent agreement with the available experimental data
      supports the reliability of the new information provided in the present work.

PMID- 21190326
TI  - Reaction-induced magnetic transition in Mn2 dimers.
AB  - The magnetic coupling between Mn atoms in Mn(2) dimers embedded in a rare gas
      matrix is antiferromagnetic but undergoes ferromagnetic transition at a higher
      temperature or when ionized to the Mn(2)(+) state. By use of density functional
      theory and hybrid functional for exchange-correlation potentials, we show that
      ferromagnetic transition can also be induced when Mn(2) reacts with Cl and/or
      BO(2). Because of their highly electronegative character, both Cl and BO(2) draw
      electrons from the Mn(2) dimer leaving it in a positively charged state. The
      resulting shrinkage in the Mn-Mn bond brought about by the removal of an
      antibonding electron causes the magnetic transition. We further show that the
      coupling between Mn atoms remains ferromagnetic when two Mn(2)Cl units are
      allowed to interact with each other. The ability to induce a magnetic transition
      through a chemical reaction provides a way to synthesize new magnetic materials.

PMID- 21190327
TI  - Expanding the library of secondary ions that distinguish lignin and
      polysaccharides in time-of-flight secondary ion mass spectrometry analysis of
      wood.
AB  - Extracted pine (Pinus spp.) wood and the holocellulose and cellulose fractions of
      pine were analyzed by time-of-flight secondary ion mass spectrometry (ToF-SIMS).
      The main sources of variation among wood constituents were elucidated by
      principal component analysis (PCA). Peaks characteristic of lignin or
      polysaccharides were identified through the combination of high mass resolution
      analyses of pine fractions and high lateral resolution image analyses
      distinguishing the lignin-rich middle lamella from the secondary cell wall layers
      in solid wood cross-sections. A collection of peaks was compiled which (1)
      extends the library of characteristic lignin and polysaccharide secondary ions in
      wood, (2) can be applied to both high and nominal mass resolution spectra, and
      (3) is free from peaks that contraindicate between wood components. The removal
      of additional peaks to avoid mass interferences with common contaminants was also
      successful. Many of the characteristic peaks were high-intensity fingerprint ions
      below m/z 100, which provided for rapid analysis of the lignin and polysaccharide
      biopolymers in woody samples. The analysis also identified important mass
      interferences with previously reported wood ions.

PMID- 21190328
TI  - On the UV-induced polymeric behavior of Chinese lacquer.
AB  - To dry Chinese lacquer rapidly for the protection and restoration of
      archeological findings coated by lacquer or excavated lacquer wares and the
      development of new application of this lacquer, we carried out UV curing
      technology to improve its curing rate using a high-pressure mercury lamp as a UV
      source in the absence of any additional photoinitiator. The effects of mainly
      specific components in Chinese lacquer sap and the role of each reactive group of
      urushiol, namely hydroxyl groups, hydrogen on the phenyl ring, and olefins in the
      side chain, in the course of UV exposure were well-investigated. The UV-cured
      Chinese lacquer films were also characterized by FT-IR, (1)H NMR, SEM, TGA, and
      Py-GC/MS. The results showed that urushiol was the main component to form Chinese
      lacquer films, and decomposed to generate the urushiol semiquinone radicals,
      which sequentially induced the polymerization of Chinese lacquer by radical
      polymerization, as well as radical substitution under UV irradiation. In
      addition, the TG analysis suggested that polysaccharide and glycoproteins were
      integrated with the UV-cured films by covalent bonding. Furthermore, this method
      could be suitable to fast cure other phenol bearing long aliphatic unsaturated
      chain, such as CNSL.

PMID- 21190329
TI  - Magnesium imide: synthesis and structure determination of an unconventional
      alkaline earth imide from decomposition of magnesium amide.
AB  - Magnesium imide (MgNH) was produced by monitoring the decomposition process of
      magnesium amide with in situ neutron diffraction. Significant changes in the
      structure of magnesium amide are detected during heat treatment and eventually
      result in the formation of crystalline MgNH. A model for the crystal structure of
      magnesium imide (MgNH) is presented for the first time. Remarkably, magnesium
      imide offers unique structural features similar to the cyclosilicate class and
      can be described as a porous solid formed by a sequence of linked chains of face
      sharing Mg(6)N(6) hexagonal prism clusters.

PMID- 21190330
TI  - Dolabellanes with antibacterial activity from the brown alga Dilophus spiralis.
AB  - Seventeen diterpenes featuring the dolabellane skeleton (1-17) were isolated from
      the organic extracts of the brown alga Dilophus spiralis. Seven compounds are new
      natural products (1, 3, 5, 6, 11, 14, 15) and eight are structurally revised (2,
      4, 7-10, 12, 13), among which three are reported for the first time from a
      natural source (4, 9, 10). The structure elucidation and the assignment of the
      relative configurations of the isolated natural products were based on detailed
      analyses of their spectroscopic data. The structure of metabolite 10 was
      confirmed by single-crystal X-ray diffraction analysis, whereas the absolute
      configurations of compounds 2, 4-10, 12, and 13 were determined using the
      modified Mosher's method on the semisynthetic product 18 and chemical
      interconversions. The antibacterial activities of compounds 1-18 were evaluated
      against six strains of Staphylococcus aureus, including multidrug- and
      methicillin-resistant variants.

PMID- 21190331
TI  - N-pyrrolylketene: a nonconjugated heteroarylketene.
AB  - N-Pyrrolylketene (5) is calculated to be destabilized and nonconjugated, with a
      preferred geometry with the pyrrolyl ring orthogonal to the ketenyl group. Ketene
      5 is generated from N-pyrrolylacetic acid (7) with use of Mukaiyama's reagent,
      and reacts with imines forming beta-lactams 10, with a product ratio correlation
      of log(cis/trans) with sigma(+). Photolysis of N-diazoacetylpyrrole (14) in MeOH
      gives methyl N-pyrrolylacetate (15) from 5 and also ester 17, evidently by
      trapping of 2-(1-pyrrolylketene) (21), formed by a new vinylogous Wolff
      rearrangement.

PMID- 21190332
TI  - Chemical bonding and aromaticity in trinuclear transition-metal halide clusters.
AB  - Trinuclear transition-metal complexes such as Re(3)X(9) (X = Cl, Br, I), with
      their uniquely featured structure among metal halides, have posed intriguing
      questions related to multicenter electron delocalization for several decades.
      Here we report a comprehensive study of the technetium halide clusters [Tc(3)(MU
      X)(3)X(6)](0/1-/2-) (X = F, Cl, Br, I), isomorphous with their rhenium congeners,
      predicted from density functional theory calculations. The chemical bonding and
      aromaticity in these clusters are analyzed using the recently developed adaptive
      natural density partitioning method, which indicates that only [Tc(3)X(9)](2-)
      clusters exhibit aromatic character, stemming from a d-orbital-based pi bond
      delocalized over the three metal centers. We also show that standard methods
      founded on the nucleus-independent chemical shift concept incorrectly predict the
      neutral Tc(3)X(9) clusters to be aromatic.

PMID- 21190333
TI  - Discrete Rh(III)/Fe(II) and Rh(III)/Fe(II)/Co(III) cyanide-bridged mixed valence
      compounds.
AB  - The heterotrinuclear complexes trans- and cis-[{cis-VI-L(15)Rh(III)(MU-NC)}{trans
      III-L(14S)Co(III)(MU-NC)}Fe(II)(CN)(4)](2+) are unprecedented examples of mixed
      valence complexes based on ferrocyanide bearing three different metal centers.
      These complexes have been assembled in a stepwise manner from their {trans-III
      L(14S)Co(III)}, {cis-VI-L(15)Rh(III)}, and {Fe(II)(CN)(6)} building blocks. The
      preparative procedure follows that found for other known discrete assemblies of
      mixed valence dinuclear Cr(III)/Fe(II) and polynuclear Co(III)/Fe(II) complexes
      of the same family. A simple slow substitution process of [Fe(II)(CN)(6)](4-) on
      inert cis-VI-[Rh(III)L(15)(OH)](2+) leads to the preparation of the new dinuclear
      mixed valence complex [{cis-VI-L(15)Rh(III)(MU-NC)}Fe(II)(CN)(5)](-) with a redox
      reactivity that parallels that found for dinuclear complexes from the same
      family. The combination of this dinuclear precursor with mononuclear trans-III
      [Co(III)L(14S)Cl](2+) enables a redox-assisted substitution on the transient
      {L(14S)Co(II)} unit to form [{cis-VI-L(15)Rh(III)(MU-NC)}{trans-III
      L(14S)Co(III)(MU-NC)}Fe(II)(CN)(4)](2+). The structure of the final cis-[{cis-VI
      L(15)Rh(III)(MU-NC)}{trans-III-L(14S)Co(III)(MU-NC)}Fe(II)(CN)(4)](2+) complex
      has been established via X-ray diffraction and fully agrees with its solution
      spectroscopy and electrochemistry data. The new species [{cis-VI-L(15)Rh(III)(MU
      NC)}{trans-III-L(14S)Co(III)(MU-NC)}Fe(II)(CN)(4)](2+) and [{cis-VI
      L(15)Rh(III)(MU-NC)}Fe(II)(CN)(5)](-) show the expected electronic spectra and
      electrochemical features typical of Class II mixed valence complexes.
      Interestingly, in the trinuclear complex, these features appear to be a simple
      addition of those for the Rh(III)/Fe(II) and Co(III)/Fe(II) moieties, despite the
      vast differences existent in the electronic spectra and electrochemical
      properties of the two isolated units.

PMID- 21190334
TI  - Clustered magnetite nanocrystals cross-linked with PEI for efficient siRNA
      delivery.
AB  - Magnetofection has been utilized as a powerful tool to enhance gene transfection
      efficiency via magnetic field-enforced cellular transport processes. The
      accelerated accumulation of nucleic acid molecules by applying an external
      magnetic force enables the rapid and improved transduction efficiency. In this
      study, we developed magnetite nanocrystal clusters (PMNCs) cross-linked with
      polyethylenimine (PEI) to magnetically trigger intracellular delivery of small
      interfering RNA (siRNA). PMNCs were produced by cross-linked assembly of catechol
      functionalized branched polyethylenimine (bPEI) around magnetite nanocrystals
      through an oil-in-water (O/W) emulsion and solvent evaporation method. The
      physical properties of PMNC were characterized by TEM, DLS, TSA, and FT-IR.
      Finely tuned formulation of clustered magnetite nanocrystals with controlled size
      and shape exhibited superior saturation of magnetization value. Magnetite
      nanocrystal clusters could form nanosized polyelectrolyte complexes with
      negatively charged siRNA molecules, enabling efficient delivery of siRNA into
      cells upon exposure to an external magnetic field within a short time. This study
      introduces a new class of magnetic nanomaterials that can be utilized for
      magnetically driven intracellular siRNA delivery.

PMID- 21190335
TI  - Synthesis of optically pure 4-fluoro-glutamines as potential metabolic imaging
      agents for tumors.
AB  - A versatile synthetic route to prepare all four stereoisomeric 4-fluoro
      glutamines was developed by exploiting a Passerini three-component reaction. The
      skeleton of 4-substituted glutamine derivatives was efficiently constructed.
      Subsequent four-step reactions, highlighted by a "neutralized" TASF fluorination,
      provided the desired products with high yields and excellent optical purity. The
      optically pure fluorine-18 labeled 4-fluoroglutamines were also successfully
      prepared using either a 18-crown-6/KHCO(3) or K[222]/K(2)CO(3) catalysis system.
      Preliminary cell uptake and inhibition studies using the 9L tumor cells and
      SF188(Bcl-xL) tumor cells (a glutamine addicted tumor derived from glioblastoma)
      provided strong evidence for their potential application in conjunction with
      positron emission tomography (PET) for in vivo imaging of tumors, which use
      glutamine as an alternative energy source.

PMID- 21190336
TI  - Molybdenum site structure of Escherichia coli YedY, a novel bacterial
      oxidoreductase.
AB  - We report a structural characterization using X-ray absorption spectroscopy of
      the molybdenum site of Escherichia coli YedY, a novel oxidoreductase related to
      be the sulfite oxidase family of molybdenum enzymes. We find that the enzyme can
      exist in Mo(V) and Mo(IV) oxidation states but cannot be readily oxidized to the
      Mo(VI) form. Mo(V) YedY has molybdenum coordination similar to that of sulfite
      oxidase, with one Mo?O at 1.71 A, three Mo-S at 2.39 A, and one Mo-OH at 2.09 A,
      which elongates to 2.20 A upon reduction to Mo(IV), indicating Mo-OH(2)
      coordination. The Mo(V) enzyme also possesses a long Mo-O coordination at 2.64 A,
      which may be due to oxygen coordination by Asn-45 O(delta), with Mo-O(delta)
      approximately trans to the Mo?O group. A comparison with sulfite oxidase
      indicates that YedY possesses a much more uniform Mo-S coordination, with a
      maximum permitted deviation of less than 0.05 A. Our results indicate that the
      YedY active site shows considerable similarity to but also important differences
      from that of reduced forms of sulfite oxidase.

PMID- 21190337
TI  - Structure of the molybdenum site in YedY, a sulfite oxidase homologue from
      Escherichia coli.
AB  - YedY from Escherichia coli is a new member of the sulfite oxidase family of
      molybdenum cofactor (Moco)-containing oxidoreductases. We investigated the atomic
      structure of the molybdenum site in YedY by X-ray absorption spectroscopy, in
      comparison to human sulfite oxidase (hSO) and to a Mo(IV) model complex. The K
      edge energy was indicative of Mo(V) in YedY, in agreement with X- and Q-band
      electron paramagnetic resonance results, whereas the hSO protein contained
      Mo(VI). In YedY and hSO, molybdenum is coordinated by two sulfur ligands from the
      molybdopterin ligand of the Moco, one thiolate sulfur of a cysteine (average Mo-S
      bond length of ~2.4 A), and one (axial) oxo ligand (Mo?O, ~1.7 A). hSO contained
      a second oxo group at Mo as expected, but in YedY, two species in about a 1:1
      ratio were found at the active site, corresponding to an equatorial Mo-OH bond
      (~2.1 A) or possibly to a shorter Mo-O(-) bond. Yet another oxygen (or nitrogen)
      at a ~2.6 A distance to Mo in YedY was identified, which could originate from a
      water molecule in the substrate binding cavity or from an amino acid residue
      close to the molybdenum site, i.e., Glu104, that is replaced by a glycine in hSO,
      or Asn45. The addition of the poor substrate dimethyl sulfoxide to YedY left the
      molybdenum coordination unchanged at high pH. In contrast, we found indications
      that the better substrate trimethylamine N-oxide and the substrate analogue
      acetone were bound at a ~2.6 A distance to the molybdenum, presumably replacing
      the equatorial oxygen ligand. These findings were used to interpret the recent
      crystal structure of YedY and bear implications for its catalytic mechanism.

PMID- 21190338
TI  - Large core-shell poly(methyl methacrylate) colloidal clusters: synthesis,
      characterization, and tracking.
AB  - We present a multistep procedure yielding large (diameter > 2 MUm) monodisperse,
      fluorescently labeled core-shell poly(methyl methacrylate) (PMMA) latex particles
      via dispersion polymerization. The particles' physical properties were controlled
      by adjusting two reaction parameters, the initiator and chain transfer agent
      concentrations, which influence the molecular weight of the PMMA. Under certain
      conditions, particles with the requisite properties for fabricating colloidal
      clusters were synthesized. The resulting clusters represent a new type of
      nonspherical colloid that can be dispersed in a density- and refractive index
      matching solvent, making them ideal for quantitative studies using confocal
      microscopy. To demonstrate the utility of our clusters, we measured the
      translational and rotational diffusion coefficients of a tetrahedral cluster by
      tracking the motion of its constituent particles in three-dimensional space. More
      broadly, our findings provide new insights concerning PMMA dispersion
      polymerization in apolar media.

PMID- 21190339
TI  - Osteoblast-like cell behavior on plasma deposited micro/nanopatterned coatings.
AB  - The behavior of cells in terms of cell-substrate and cell-cell interaction is
      dramatically affected by topographical characteristics as shape, height, and
      distance, encountered in their physiological environment. The combination of
      chemistry and topography of a biomaterial surface influences in turns, important
      biological responses as inflammatory events at tissue-implant interface,
      angiogenesis, and differentiation of cells. By disentangling the effect of
      material chemistry from the topographical one, the possibility of controlling the
      cell behavior can be provided. In this paper, surfaces with different roughness
      and morphology were produced by radiofrequency (RF, 13.56 MHz) glow discharges,
      fed with hexafluoropropylene oxide (C(3)F(6)O), in a single process. Coatings
      with different micro/nanopatterns and the same uppermost chemical composition
      were produced by combining two plasma deposition processes, with C(3)F(6)O and
      tetrafluoroethylene (C(2)F(4)), respectively. The behavior of osteoblast-like
      cells toward these substrates clearly shows a strict dependence of cell adhesion
      and proliferation on surface roughness and morphology.

PMID- 21190340
TI  - Complex coacervation-controlled release from monoolein cubic phase containing
      silk fibroin and alginate.
AB  - pH-dependent release from monoolein (MO) cubic phase was obtained by taking
      advantage of complex coacervation between hydrophobically modified alginate
      (HmAL) and hydrophobically modified silk fibroin (HmSF) in the water channels.
      The degree of coacervation was investigated at pH 3.0 by a light scattering
      method and the maximum coacervation was observed when the ratio of HmAL to HmSF
      was 1:15. The degree of coacervation dramatically decreased (from 581.2 to 5.2 nm
      in size and from 267.9 to 12.3 nm in Kcps) when the pH of medium increased from
      3.0 to 5.0. The % release in 100 h of FITC-dextran increased from 2.42 to 7.20%
      when pH of release medium increased from 3.0 to 9.0. Under acidic conditions,
      coacervate will block the water channels of cubic phase, suppressing the release.
      As the pH of release medium increases, the coacervate will dissolve, resulting in
      a higher release. The cubic phase could be exploited as a pH-sensitive carrier
      for the oral delivery of an acid-labile drug.

PMID- 21190341
TI  - Self-assembly and enhanced photocatalytic properties of BiOI hollow microspheres
      via a reactable ionic liquid.
AB  - BiOI uniform flowerlike hollow microspheres with a hole in its surface structures
      have been successfully synthesized through an EG-assisted solvothermal process in
      the presence of ionic liquid 1-butyl-3-methylimidazolium iodine ([Bmim]I). The as
      prepared samples were characterized by X-ray diffraction (XRD), scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray
      spectroscopy (EDS), nitrogen sorption, and diffuse reflectance spectroscopy
      (DRS). A possible formation mechanism for the growth of hollow microspheres was
      discussed. During the reactive process, ionic liquid not only acted as solvents
      and templates but also as an I source for the fabrication of BiOI hollow
      microspheres and was vital for the structure of hollow microspheres.
      Additionally, we evaluated the photocatalytic activities of BiOI on the
      degradation of methyl orange (MO) under visible light irradiation and found that
      as-prepared BiOI hollow microspheres exhibited higher photocatalytic activity
      than BiOI nanoplates and TiO(2) (Degussa, P25) did. On the basis of such
      analysis, it can be assumed that the enhanced photocatalytic activities of BiOI
      hollow microspheres could be ascribed to its energy band structure, high BET
      surface area, high surface-to-volume ratios, and light absorbance.

PMID- 21190342
TI  - TEMPO-oxidized cellulose nanofibrils dispersed in organic solvents.

PMID- 21190343
TI  - Stabilization of embedded Pt nanoparticles in the novel nanostructure carbon
      materials.
AB  - An extremely durable and highly active Pt catalyst has been successfully prepared
      by embedding Pt(0) nanoparticles inside the pores of the nitrogen-dotted porous
      carbon layer surrounding carbon nanotubes (Pt@NC-CNT). The Pt@NC-CNT catalyst has
      a high BET surface area of 271 m(2) g(-1) (62 m(2) g(-1) for Pt/XC-72) and
      comparably high electrochemically active surface area of 64.3 m(2) g(-1) (68.2
      m(2) g(-1) for Pt/XC-72). The prepared Pt nanoparticles are small in size (2.8 +/
      1.3 nm) and have a strong interaction of nitrogen to platinum, as evidenced by
      the binding energy observed at 399.5 eV. The maximum current densities (I(f))
      during methanol oxidation observed for Pt@NC-CNT (13.2 mA cm(-1)) is 1.2 times
      higher than that of Pt/XC-72 (10.8 mA cm(-1)) catalysts. Remarkably, in the long
      term durability test, the I(f) after 1000 cycles for Pt@NC-CNT decreased to 10.6
      mA cm(-1) compared with Pt/XC-72, which decreased to 2.6 mA cm(-2). This means
      that the Pt@NC-CNT catalyst has a tremendously stable electrocatalytic activity
      for MOR because of the unique structure of Pt@NC-CNT formed in this novel
      synthesis technique.

PMID- 21190344
TI  - Liquid interface functionalized by an ion extractant: the case of Winsor III
      microemulsions.
AB  - The present work shows for the first time that tributylphosphate (TBP), the major
      ion extractant used in the reprocessing of spent nuclear fuel, acts efficiently
      as a cosurfactant in the formation of three-phase microemulsions. The system is
      composed of water, dodecane, TBP, and an extremely hydrophilic sugar surfactant,
      n-octyl-beta-glucoside. The investigation of the three-phase region (Winsor III),
      the so-called "fish-cut" diagrams, revealed that TBP exhibits cosurfactant
      behavior comparable to that of classical cosurfactants n-pentanol and n-hexanol.
      Upon increasing the cosurfactant/surfactant molar ratio, TBP appears to be more
      efficient than single-chain alcohols in raising the spontaneous curvature of the
      adsorbed surfactant film toward oil. This is a direct consequence of the
      different lateral packing of TBP and n-pentanol or n-hexanol in the mixed
      surfactant film, with TBP having three alkyl chains and so a higher hydrophobic
      volume than those n-alcohols. This property is underlined by the interfacial film
      composition, which is determined by the chemical analysis of the excess phases.
      It gives a surfactant to cosurfactant molar ratio of 1:1 for TBP and 1:3 for n
      hexanol. Moreover, the local microstructure of the microemulsion becomes
      dependent on the addition of salt when n-alcohol is replaced by TBP. A specific
      salt effect is also observed and rationalized in terms of the complexing property
      of TBP and Hofmeister's effects. Treatment of the small-angle neutron scattering
      (SANS) data gives access to (i) the length scales characterizing the
      microemulsions (i.e., the persistence length, xi, and aqueous or organic domain
      sizes, D*) and (ii) the specific surface, Sigma. It results that a subtle change
      is highlighted in the TBP microemulsion structure, in terms of connectivity,
      according to the type of salt added.

PMID- 21190345
TI  - Converting poorly soluble materials into stable aqueous nanocolloids.
AB  - Aqueous nanocolloids of poorly soluble materials were produced via sonicated
      layer-by-layer (LbL) encapsulation with polycation / polyanion shells. Synergy of
      simultaneous breaking powder particles with ultrasonication and coating them with
      polycations allowed for the production of 150-200 nm diameter polyelectrolyte
      coated nanoparticles with sufficient surface electrical potential for colloidal
      stability. This technique increases water dispersibility of low soluble materials
      ranging from anticancer drugs to anticorrosion agents, dyes and inorganic salts.

PMID- 21190346
TI  - Enhanced optical and nonlinear optical responses in a polyelectrolyte templated
      Langmuir-Blodgett film.
AB  - Optical and nonlinear optical properties like fluorescence and second harmonic
      generation (SHG) of molecular materials can be strongly influenced by the mode of
      assembly of the molecules. The Langmuir-Blodgett (LB) technique is an elegant
      route to the controlled assembly of molecules in ultrathin films, and
      complexation of ionic amphiphiles in the Langmuir film by polyions introduced in
      the aqueous subphase provides a simple and efficient access to further control,
      stabilization, and optimization. The monolayer LB film of the hemicyanine-based
      amphiphile, N-n-octadecyl-4-[2-(4-(N,N
      ethyloctadecylamino)phenyl)ethenyl]pyridinium possessing a "tail-head-tail"
      structure, shows fluorescence as well as SHG response. The concomitant
      enhancement of both of these linear and nonlinear optical attributes is achieved
      through templating with the polyanion of carboxymethylcellulose. Brewster angle
      and atomic force microscopy reveal the influence of polyelectrolyte templating on
      the morphology of the Langmuir and LB films. Polarized absorption and
      fluorescence spectroscopy provide insight into the impact of complexation with
      the polyelectrolyte on the orientation and deaggregation of the hemicyanine
      headgroup leading to fluorescence and SHG enhancement in the LB film.

PMID- 21190347
TI  - An experimental and molecular simulation study of the adsorption of carbon
      dioxide and methane in nanoporous carbons in the presence of water.
AB  - The adsorption of carbon dioxide and methane in nanoporous carbons in the
      presence of water is studied using experiments and molecular simulations. For all
      amounts of adsorbed water molecules, the adsorption isotherms for carbon dioxide
      and methane resemble those obtained for pure fluids. The pore filling mechanism
      does not seem to be affected by the presence of the water molecules. Moreover,
      the pressure at which the maximum adsorbed amount of methane or carbon dioxide is
      reached is nearly insensitive to the loading of preadsorbed water molecules. In
      contrast, the adsorbed amount of methane or carbon dioxide decreases linearly
      with the number of guest water molecules. Typical molecular configurations
      obtained using molecular simulation indicate that the water molecules form
      isolated clusters within the host porous carbon due to the nonfavorable
      interaction between carbon dioxide or methane and water.

PMID- 21190349
TI  - Strands, networks, and continents from polystyrene dewetting at the air-water
      interface: implications for amphiphilic block copolymer self-assembly.
AB  - We demonstrate that nanoscale aggregates similar to those formed via amphiphilic
      block copolymer self-assembly at the air-water interface, including strands,
      networks, and continents, can be generated by the simple spreading of PS
      homopolymer solutions on water. Two different PS homopolymers of different
      molecular weight (PS-405k, M(n) = 405 000 g mol(-1) and PS-33k, M(n) = 33 000 g
      mol(-1)) are spread at the air-water interface at various spreading
      concentrations ranging from 0.25 to 3.0 mg/mL. Aggregate formation is driven by
      PS dewetting from water as the spreading solvent evaporates. We propose that a
      high spreading concentration or a high molecular weight lead to chain
      entanglements that restrict macromolecular mobility in the solution, enabling the
      kinetic trapping of nanostructures associated with early and intermediate stages
      of PS dewetting. Comparison of PS-405k with a mainly hydrophobic PS-b-PEO block
      copolymer of similar molecular weight (PSEO-392k, M(n) = 392 000 g mol(-1), 2.0
      wt % PEO) allows the effect of a relatively short surface active block on
      aggregate formation to be investigated. We show that whereas the PEO block is not
      a required component for the formation of strands and other nonglobular
      aggregates, it does increase the number of these aggregates at a given spreading
      concentration and decreases the minimum spreading concentration at which these
      aggregates are observed, along with decreasing the dimensions and polydispersity
      of specific surface features. The results provide supporting evidence for the
      role of PS dewetting in the generation of multiple PS-b-PEO aggregate
      morphologies at the air-water interface, as originally described in earlier paper
      from our group.

PMID- 21190348
TI  - Integrin-targeting block copolymer probes for two-photon fluorescence bioimaging.
AB  - Targeted molecular imaging with two-photon fluorescence microscopy (2PFM) is a
      powerful technique for chemical biology and, potentially, for noninvasive
      diagnosis and treatment of a number of diseases. The synthesis, photophysical
      studies, and bioimaging are reported for a versatile norbornene-based block
      copolymer multifunctional scaffold containing biocompatible (PEG), two-photon
      fluorescent dyes (fluorenyl) and targeting (cyclic-RGD peptide) moieties. The two
      bioconjugates, containing two different fluorenyl dyes and cRGDfK covalently
      attached to the polymer probe, formed a spherical micelle and self-assembled
      structure in water, for which size was analyzed by transmission electron
      microscopy (TEM) and dynamic light scattering (DLS). Cell viability and 2PFM
      imaging of human epithelial U87MG cell lines that overexpress alpha(v)beta(3)
      integrin was performed via incubation with the new probes, along with negative
      control studies using MCF-7 breast cancer cells and blocking experiments. 2PFM
      microscopy confirmed the high selectivity of the biocompatible probe in the
      integrin-rich area in the U87MF cells while blocking as well as negative control
      MCF-7 experiments confirmed the integrin-targeting ability of the new probes.

PMID- 21190350
TI  - Olefin epoxidation by molybdenum peroxo compound: molecular mechanism
      characterized by the electron localization function and catastrophe theory.
AB  - The oxygen atom transfer reaction from the Mimoun-type complex MoO(eta(2)
      O(2))(2)OPH(3) to ethylene C(2)H(4) affording oxirane C(2)H(4)O has been
      investigated within the framework of the Bonding Evolution Theory in which the
      corresponding molecular mechanism is characterized by the topological analysis of
      the electron localization function (ELF) and Thom's catastrophe theory (CT).
      Topological analysis of ELF and electron density analysis reveals that all Mo-O
      bonds in MoO(eta(2)-O(2))(2)OPH(3) and MoO(2)(eta(2)-O(2))OPH(3) belong to closed
      shell type interactions though negative values of total energy densities
      E(e)(r(BCP)) imply some covalent contribution. The peroxo O(i)-O(j) bonds are
      characterized as charge-shift or protocovalent species in which pairs of
      monosynaptic basins V(3)(O(i)), V(3)(O(j)) with a small electron population of
      ~0.25e each, are localized between core basins C(O(i)), C(O(j)). The oxygen
      transfer reaction from molybdenum diperoxo complex MoO(eta(2)-O(2))(2)OPH(3) to
      C(2)H(4) system can be described by the following consecutive chemical events:
      (a) protocovalent peroxo O(2)-O(1) bond breaking, (b) reduction of the double
      C(1)=C(2) bond to single C(1)-C(2) bond in ethylene, (c) displacement of oxygen
      O(1) with two nonbonding basins, V(i=1,2)(O(1)), (d) increase of a number of the
      nonbonding basins to three (V(i=1,2,4)(O(1))); (e) reorganization and reduction
      in the number of nonbonding basis to two basins (V(i=1,4)(O(1))) resembling the
      ELF-topology of the nonbonding electron density in oxirane, (e) formation of the
      first O(1)-C(2) bond in oxirane, (f) C(2)-O(1)-C(2) ring closure, (g) formation
      of singular nonbonding basin V(O(2)) in new Mo=O(2) bond. The oxygen atom is
      transferred as an anionic moiety carrying a rather small electronic charge
      ranging from 0.5 to 0.7e.

PMID- 21190351
TI  - Physicochemical characterization of nanotemplate engineered solid lipid
      nanoparticles.
AB  - As the physicochemical characteristics of solid lipid nanoparticles (SLNs) play a
      critical role in their success, it is important to understand how the materials
      and process used in their preparation affect these properties. In this study, two
      stearyl alcohol-based formulations were prepared using nanotemplate engineering
      technology and characterized. Both formulations were of a small particle size
      (<100 nm), ellipsoidal shape, and low polydispersity. (1)H NMR spectroscopy
      confirmed that the SLNs have the expected solid core structure and PEGylated
      surface. Analysis of the bulk materials indicated that a number of complex
      interactions are present among the SLN components, including a eutectic between
      stearyl alcohol and Brij 78. The decreased crystallinity resulting from these
      interactions may allow for enhanced drug loading. Physiological stability was
      identified and confirmed as a potential problem due to the low melting point of
      the eutectic. However, it is expected that with appropriate formulation
      modifications nanotemplate engineered SLNs will possess the properties necessary
      for a successful drug delivery system.

PMID- 21190352
TI  - First synthesis of C. difficile PS-II cell wall polysaccharide repeating unit.
AB  - Clostridium difficile is the most commonly diagnosed cause of nosocomial diarrhea
      with increasing incidence and mortality among elderly and hospitalized patients.
      We report the first synthesis of the surface polysaccharide PS-II repeating unit
      and its nonphosphorylated analogue, with a linker for conjugation, via a (4 + 2)
      convergent approach from a common AB(D)C tetrasaccharide intermediate.

PMID- 21190353
TI  - Excited-state intramolecular proton transfer in hydroxyoxime-based chemical
      sensors.
AB  - The electronic structure of a series of beta-hydroxy-oximes, with different
      aromatic cores (naphthalene, pyrene, coumarin, pyridine) between the oxime and
      the hydroxyl groups, has been investigated by time-dependent density functional
      theory (TDDFT) and of the naphthalene-based oxime, in addition, by resolution-of
      identity second-order perturbative coupled cluster (RICC2) calculations with
      basis sets up to augmented triple-zeta quality. The particular systems have been
      proposed as fluorescent sensors of organophosphorus (OP) nerve agents, with
      enhancement of fluorescence accompanying the sensing of OP agents. It is found
      that the experimentally observed fluorescence quenching of the oxime sensors in
      their initial form can be attributed to intramolecular proton transfer upon
      excitation from the beta-hydroxyl group to the nitrogen atom, thus forming a
      weakly emitting hydroxylaminoquinoid.

PMID- 21190354
TI  - An atom-economical access to beta-heteroarylated ketones from propargylic
      alcohols via tandem ruthenium/indium catalysis.
AB  - The direct and chemoselective synthesis of beta-heteroarylated ketones from
      secondary propargyl alcohols through tandem Ru/In catalysis is reported. Both
      electron-rich and neutral heteroarenes, such as furans and indoles, efficiently
      undergo the redox isomerization/conjugate addition (RICA) sequence to provide the
      corresponding adducts in yields of up to 97%.

PMID- 21190355
TI  - Effect of crowding by dextrans on the hydrolysis of N-Succinyl-L-phenyl-Ala-p
      nitroanilide catalyzed by alpha-chymotrypsin.
AB  - Traditionally, studies on the diffusion-controlled reaction of biological
      macromolecules have been carried out in dilute solutions (in vitro). However, in
      an intracellular environment (in vivo), there is a high concentration of
      macromolecules, which results in nonspecific interactions (macromolecular
      crowding). This affects the kinetics and thermodynamics of the reactions that
      occur in these systems. In this paper, we study the crowding effect of large
      macromolecules on the reaction rates of the hydrolysis of N-succinyl-L-phenyl-Ala
      p-nitroanilide catalyzed by alpha-chymotrypsin, by adding dextrans of various
      molecular weights to the reaction solutions. The results indicate that the volume
      occupied by the crowding agent, but not its size, plays an important role in the
      rate of this reaction. A v(max) decay and a K(m) increase were obtained when the
      dextran concentration in the sample was increased. The increase in K(m) can be
      attributed to the slowing of protein diffusion, due to the presence of crowding.
      Whereas the decrease in v(max) could be explained by the effect of mixed
      inhibition by product, which is enhanced in crowded media. As far as we know,
      this is the first reported experiment on the crowding effect in an enzymatic
      reaction with a mixed inhibition by product.

PMID- 21190356
TI  - Understanding chloroquine action at the molecular level in antimalarial therapy:
      X-ray absorption studies in dimethyl sulfoxide solution.
AB  - X-ray absorption spectroscopy is used to determine the local atomic structure
      around the iron atom from a soluble synthetic analogue of malaria pigment
      (hemozoin), cf. ferrimesoporphyrin IX of mesohematin anhydride, in the absence or
      presence of chloroquine (CQ) in dimethyl sulfoxide (DMSO). Of particular note are
      the CQ-induced changes in the structure of mesohematin anhydride, which might
      confirm the formation of CQ-ferrimesoporphyrin IX complex. Examination of
      solutions of mesohematin anhydride dissolved in DMSO reveals preservation of the
      dimerlike structure with the central iron atoms of the ferric porphyrin IX
      reciprocally linked by propionate side chains, which is typical for hematin
      anhydride (beta-hematin). In the presence of CQ, additional light atoms, such as
      nitrogen, carbon, and oxygen, were detected surrounding the iron in a distance
      ranging from 2.48 to 3.77 A. The changes introduced by CQ in DMSO are different
      from that observed in the acetic acid solution.

PMID- 21190357
TI  - Sequential charge separation in two axially linked phenothiazine-aluminum(III)
      porphyrin-fullerene triads.
AB  - New supramolecular triads (PTZpy->AlPor-C(60), TPTZpy->AlPor-C(60)), containing
      aluminum(III) porphyrin (AlPor), fullerene (C(60)), and phenothiazine
      (phenothiazine = PTZ, 2-methylthiophenothaizine = TPTZ) have been constructed. In
      these triads the fullerene and phenothiazine units are bound axially to opposite
      faces of the porphyrin plane via covalent and coordination bonds, respectively.
      The ground- and excited-state properties of the triads and reference dyads are
      studied using steady-state and time-resolved spectroscopic techniques. The time
      resolved data show that photoexcitation results in charge separation from the
      excited singlet state of the porphyrin to the C(60) unit, generating (Donor)py
      >AlPor(*+)-C(60)(*-), Donor = PTZ and TPTZ. A subsequent hole shift from the
      porphyrin to phenothiazine generates the charge-separated state (Donor)(*+)py
      >AlPor-C(60)(*-). The lifetime of the charge separation exhibits a modest
      increase from 39 ns in the absence of the donor to 100 ns in PTZpy->AlPor-C(60)
      and 83 ns in TPTZpy->AlPor-C(60). These lifetimes are discussed in terms of the
      electronic coupling between phenothiazine, the porphyrin, and C(60).

PMID- 21190359
TI  - A high-pressure infrared spectroscopic study on the interaction of ionic liquids
      with PEO-PPO-PEO block copolymers and 1,4-dioxane.
AB  - We have investigated the effect of pressure on imidazolium C-H---O interactions
      in 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide (EMI(+)TFSA(
      ))/L64 and EMI(+)TFSA(-)/1,4-dioxane mixtures. The addition of Pluronic L64 to
      EMI(+)TFSA(-) leads to appreciable changes in band frequencies and shapes of the
      imidazolium C-H stretching bands. A possible explanation is the formation of C-H-
      -O interactions between imidazolium C-H groups and oxygen atoms of polyethylene
      oxides (PEOs). In other words, L64 can be added to change the relative
      contribution of the isolated and associated components of EMI(+)TFSA(-). In
      contrast to L64, the oxygen atoms of 1,4-dioxane cannot perturb the local
      structures of imidazolium C-H groups of EMI(+)TFSA(-) and the association
      configuration is still favored in the presence of 1,4-dioxane. As the pressure is
      elevated, 1,4-dioxane molecules tend to associate with themselves and TFSA(-)
      interacts with EMI(+) to form associated configurations. Our results suggest the
      formation of association between EMI(+) cation and L64 and the complexes are
      stable up to the pressure of 2.5 GPa.

PMID- 21190358
TI  - Ion and solvent density distributions around canonical B-DNA from integral
      equations.
AB  - We calculate the water and ion spatial distributions around charged
      oligonucleotides using a renormalized three-dimensional reference interaction
      site theory coupled with the HNC closure. Our goal is to understand the balance
      between inter-DNA strand forces and solvation forces as a function of
      oligonucleotide length in the short strand limit. The DNA is considered in
      aqueous electrolyte solutions of 1 M KCl, 0.1 M KCl, or 0.1 M NaCl. The current
      theoretical results are compared to molecular dynamics (MD) simulations and
      experiments. It is found that the integral equation (IE) theory replicates the MD
      and the experimental results for the base-specific hydration patterns in both the
      major and the minor grooves. We are also able to discern characteristic
      structural pattern differences between Na(+) and K(+) ions. When compared to
      Poisson-Boltzmann methods, the IE theory, like simulation, predicts a richly
      structured ion environment, which is better described as multilayer rather than
      double layer.

PMID- 21190360
TI  - Silver-coated dye-embedded silica beads: a core material of dual tagging sensors
      based on fluorescence and Raman scattering.
AB  - We have developed a new type of dual-tag sensor for immunoassays, operating via
      both fluorescence and surface-enhanced Raman scattering (SERS). A one-shot
      fluorescence image over the whole specimen allows us to save considerable time
      because any unnecessary time-consuming SERS measurements can be avoided from the
      signature of the fluorescence. Dye-embedded silica beads are prepared initially,
      and then SERS-active silver is coated onto them via a very simple electroless
      plating method. The Raman markers are subsequently assembled onto the Ag-coated
      silica beads, after which they are stabilized by silanization via a biomimetic
      process in which a poly(allylamine hydrochloride) layer formed on the Raman
      markers by a layer-by-layer deposition method acting as a scaffold for guiding
      silicification. In the final stage, specific antibodies are attached to the
      silica surface in order to detect target antigens. The fluorescence signal of the
      embedded dye can be used as a fast readout system of molecular recognition,
      whereas the SERS signals are subsequently used as the signature of specific
      molecular interactions. In this way, the antibody-grafted particles were found to
      recognize antigens down to 1 * 10(-10) g mL(-1) solely by the SERS peaks of the
      Raman markers.

PMID- 21190361
TI  - Iodine isotopes (129I and 127I) in the Baltic Proper, Kattegat, and Skagerrak
      basins.
AB  - Radioactive anthropogenic pollution has raised concerns about the present and
      future environmental status of the semienclosed Baltic Sea. We here study the
      distribution and inventory of the anthropogenic radioactive (129)I in water depth
      profiles collected from 16 sites in August 2006 and 19 sites in April 2007 in the
      Baltic Proper and related Kattegat and Skagerrak basins. The results reveal
      considerable differences of (129)I concentration in terms of spatial and temporal
      variability and expose relatively high concentrations in the deep waters.
      Variability in the concentration of (127)I, stable natural isotope of iodine,
      seems to follow changes in the seawater salinity, but in oxygen-poor bottom
      waters sediment diagenetic release may contribute to the concentration of both
      isotopes in the water body. Inventory estimates show that (129)I in August 2006
      (24.2 +/- 15.4 kg) is higher than that in April 2007 (14.4 +/- 8.3 kg) within the
      southern and central Baltic Proper whereas almost a constant load occurs in the
      Kattegat Basin. Calculated model inventory shows correspondence to empirical data
      and provides a guideline for future environmental assessment on the impact of
      (129)I load in the studied region.

PMID- 21190362
TI  - Application of artificial neural network (ANN) and partial least-squares
      regression (PLSR) to predict the changes of anthocyanins, ascorbic acid, Total
      phenols, flavonoids, and antioxidant activity during storage of red bayberry
      juice based on fractal analysis and red, green, and blue (RGB) intensity values.
AB  - Artificial neural network (ANN) and partial least-squares regression (PLSR)
      models were developed to predict the changes of anthocyanin (AC), ascorbic acid
      (AA), total phenols (TP), total flavonoid (TF), and DPPH radical scavenging
      activity (SA) in bayberry juice during storage based on fractal analysis (FA) and
      red, green, and blue (RGB) intensity values. The results show the root mean
      squared error (RMSE) of ANN-FA decreased 2.44 and 12.45% for AC (RMSE = 18.673
      mg/100 mL, R(2) = 0.939) and AA (RMSE = 8.694 mg/100 mL, R(2) = 0.935) compared
      with PLSR-RGB, respectively. In addition, PLSR-FA (RMSE = 5.966%, R(2) = 0.958)
      showed a 12.01% decrease in the RMSE compared with PLSR-RGB for predicting SA.
      For the prediction of TP and TF, however, both models showed poor performances
      based on FA and RGB. Therefore, ANN and PLSR combined with FA may be a potential
      method for quality evaluation of bayberry juice during processing, storage, and
      distribution, but the selection of the most adequate model is of great importance
      to predict different nutritional components.

PMID- 21190363
TI  - Planar-chiral pillar[5]arene: chiral switches induced by multiexternal stimulus
      of temperature, solvents, and addition of achiral guest molecule.
AB  - We synthesized chiral-substituents modified pillar[5]arene for the first time.
      The chiral-substituents modified pillar[5]arene showed planar chirality and
      interconversion between (pS) and (pR) forms took place quickly. The planar
      chirality was switched by temperature, solvents, and addition of achiral guest.
      As the measurement temperature increased, the diastereomeric excess was
      decreased. The diastereomeric excesses were high in low-permittivity solvents,
      while a low diastereomeric excess was observed in high-permittivity solvents.
      Addition of achiral guest induced an increase of negative CD intensities.

PMID- 21190364
TI  - Hemisynthesis of dihydroumbellulols from umbellulone: new cooling compounds.
AB  - Although menthol is a common ingredient used in food products, other molecules
      also evoke coolness through stimulation of the somatosensory system. To discover
      new molecules having cooling properties, we virtually screened the chemical
      structures of terpenes and sesquiterpenes to find structures that are similar to
      (-)-menthol. We realized that dihydroumbellulols could be good candidates.
      Although their occurrence was reported in Hyptis pectinata Poit, we were unable
      to obtain these molecules from the plant or to prove their natural occurrence.
      Therefore, we extracted (-)-(R)-umbellulone from Umbellularia californica Nutt.
      The (-)-(R)-umbellulone was reduced to prepare (1R,2R/S)-1-isopropyl-4
      methylbicyclo[3.1.0]hex-3-en-2-ol, (1R,4R/S)-1-isopropyl-4
      methylbicyclo[3.1.0]hexan-2-one, and (1R,2RS,4RS)-1-isopropyl-4
      methylbicyclo[3.1.0]hexan-2-ols, named dihydroumbellulols. Sensory analysis
      suggested that (1R,2R,4S)-dihydroumbellulol has a pleasant, trigeminal cooling
      effect, about 2-3 times less cooling than (-)-menthol, with a weak odor slightly
      reminiscent of eucalyptol. In addition, a previously unreported compound was
      discovered, (-)-(1R)-1-isopropyl-4-methylenebicyclo[3.1.0]hexan-2-one.

PMID- 21190365
TI  - Dications of 3-phenyl-indenylidene dibenzo[a.d]cycloheptene: the role of charge
      in the antiaromaticity of cationic systems.
AB  - Dications of 9-(3-phenyl-1H-inden-1-ylidene)-5H-dibenzo[a,d]cycloheptene, 5(2+),
      were prepared by oxidation with SbF(5) in SO(2)ClF, and their magnetic behavior
      was compared to dications of 9-(3-phenyl-1H-inden-1-ylidene)-9H-fluorene, 2(2+).
      The good correlation between the experimental (1)H NMR shifts for the dications
      that were oxidized cleanly and the chemical shifts calculated by the GAIO method
      supported the use of the nucleus independent chemical shifts, NICS, to evaluate
      the antiaromaticity of the indenyl systems of 2(2+)/5(2+) and their unsubstituted
      parent compounds, 6(2+) and 7(2+), as well as the antiaromaticity of the
      fluorenyl system of 2(2+)/7(2+) and the aromaticity of the dibenzotropylium
      system of 5(2+)/6(2+). Antiaromaticity was shown to be directly related to the
      amount of charge in the antiaromatic systems, with the antiaromatic systems more
      responsive to changes in the calculated NBO charge than the aromatic systems. The
      antiaromaticity was also shown to be directly related to the amount of
      delocalization in the ring system. The aromaticity of the dibenzotropylium system
      was much less responsive to changes in the amount of charge in the tropylium
      system, because the aromatic system was much more completely delocalized. Thus,
      antiaromatic species are more sensitive probes of delocalization than aromatic
      ones.

PMID- 21190366
TI  - Titanocene(III)-promoted Barbier-type crotylation of carbonyl compounds.
AB  - A mild, highly regio- and stereoselective method for the crotylation of aldehydes
      and ketones mediated/catalyzed by titanocene(III) is described. Optimized
      conditions permit the selective generation of gamma-adducts in high yields
      together with high stereoselectivity, with a predominance of anti stereoisomers.

PMID- 21190367
TI  - Hexaphenylbenzene as a rigid template for the straightforward syntheses of "star
      shaped" glycodendrimers.
AB  - Original glycodendrimers emanating from propargylated hexaphenylbenzene cores and
      containing up to 54 peripheral sugar ligands have been synthesized by Cu(I)
      catalyzed [1,3]-dipolar cycloadditions using both convergent and divergent
      approaches.

PMID- 21190368
TI  - Inhibition of lymphoid tyrosine phosphatase by benzofuran salicylic acids.
AB  - The lymphoid tyrosine phosphatase (Lyp, PTPN22) is a critical negative regulator
      of T cell antigen receptor (TCR) signaling. A single-nucleotide polymorphism
      (SNP) in the ptpn22 gene correlates with the incidence of various autoimmune
      diseases, including type 1 diabetes, rheumatoid arthritis, and systemic lupus
      erythematosus. Since the disease-associated allele is a more potent inhibitor of
      TCR signaling, specific Lyp inhibitors may become valuable in treating
      autoimmunity. Using a structure-based approach, we synthesized a library of 34
      compounds that inhibited Lyp with IC(50) values between 0.27 and 6.2 MUM. A
      reporter assay was employed to screen for compounds that enhanced TCR signaling
      in cells, and several inhibitors displayed a dose-dependent, activating effect.
      Subsequent probing for Lyp's direct physiological targets by immunoblot analysis
      confirmed the ability of the compounds to inhibit Lyp in T cells. Selectivity
      profiling against closely related tyrosine phosphatases and in silico docking
      studies with the crystal structure of Lyp yielded valuable information for the
      design of Lyp-specific compounds.

PMID- 21190369
TI  - Design, synthesis, and biological activity of novel 5-((arylfuran/1H-pyrrol-2
      yl)methylene)-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-4-ones as HIV-1
      fusion inhibitors targeting gp41.
AB  - On the basis of our earlier molecular docking analysis, we designed and
      synthesized 5-((arylfuran/1H-pyrrol-2-yl)methylene)-2-thioxo-3-(3
      (trifluoromethyl)phenyl)thiazolidin-4-ones (12a-o) as HIV-1 entry inhibitors.
      Compounds 12a-o effectively inhibited infection by both laboratory-adapted and
      primary HIV-1 strains and blocked HIV-1 mediated cell-cell fusion and gp41 six
      helix bundle formation. Molecular docking analyses on two highly active
      inhibitors, 12b, containing a carboxylic acid group, and 12m, containing a
      tetrazole group, indicated that they both fit snugly into the hydrophobic cavity
      of HIV-1 gp41 from which each has important ionic interactions with lysine 574
      (K574). By contrast, molecular docking of 12i, a less active compound containing
      a pyrrole instead of a furan ring, indicated a completely different orientation
      from 12b and 12m and missed critical interactions.

PMID- 21190370
TI  - Natural products as molecular messengers.
AB  - The chemistry of naturally occurring compounds has long been pursued in the
      search for medicines, dyes, pesticides, flavors, and fragrances. In addition, the
      deeper aim of understanding life itself as a chemical phenomenon has motivated
      generations of scientists. One consequence of such studies has been the
      realization that natural products often serve central roles as biological
      signaling agents. We consider natural products from the viewpoint of the
      organisms that produce and/or respond to them and suggest how a naturally
      occurring compound may acquire its role in chemical communication.

PMID- 21190371
TI  - Polycyclic compounds by Ugi-Pictet-Spengler sequence.
AB  - A general approach to architecturally stimulating polycyclic structures is
      described by a concise, two-step procedure including a Ugi MCR (multicomponent
      reaction) and a subsequent Pictet-Spengler reaction starting from
      phenylethylamine-derived isocyanides. Ten compounds are described in full
      experimental detail, and yields range from medium to very good. Some of the
      reactions run with a high degree of stereoselectivity. The compound structures
      resemble steroid hormones and alkaloid classes of natural products. Exemplary
      products have been fully reduced to their tertiary amines. As such they could
      potentially become interesting biological probes.

PMID- 21190372
TI  - Molecular recognition of melamine by vesicles spontaneously formed from orotic
      acid derived bolaamphiphiles.
AB  - Molecular recognition by means of multiple hydrogen bonds is of great importance
      in biological functions. In this paper, an orotic acid derived bolaamphiphile
      1,12-diaminododecane diorotate (DDO) with molecular recognition function moieties
      was designed. Both self-aggregation behavior and molecular recognition with
      melamine were extensively examined. This bolaamphiphile itself can form vesicles
      easily in aqueous solutions at 25  degrees C. Steady-state fluorescence was used
      to characterize the detailed molecular recognition process. The fluorescence of
      melamine was quenched more effectively by the spontaneously formed vesicles than
      by the monomers of the surfactant. Two mechanisms were involved in the
      fluorescence quench process. At lower concentration, the fluorescence of melamine
      was found to be quenched by static complex formation. While at higher
      concentration, both static and dynamic quenching mechanisms coexisted in
      interaction process. Thermodynamic parameters measured by isothermal titration
      calorimetry showed that the free energy (DeltaG) is negative, indicating that
      binding of DDO molecules with melamine is favorable energetically. Hydrogen
      bonded interactions contribute comparatively a lot for the DDO monomer binding
      with melamine; at the higher concentration above its critical aggregation
      concentration, the dissociation of the aggregates take place and lead to an
      entropically driven molecular recognition process. As complicated binding sites
      can be constructed through self-assembly at the vesicle interface rather than
      simple molecular modules, this bolaamphiphile with the molecular recognition
      functional group may make it possible to generate well-defined recognition sites
      to mimic biomolecular receptors. Moreover, the present research will give a guide
      to design chemosensors for melamine detection based on molecular recognition.

PMID- 21190373
TI  - Sensing polymer/DNA polyplex dissociation using quantum dot fluorophores.
AB  - We characterized the dissociation of polymer/DNA polyplexes designed for gene
      delivery using water-soluble quantum dots (QDs). A pH-responsive pentablock
      copolymer was designed to form stable complexes with plasmid DNA via tertiary
      amine segments. Dissociation of the polyplex was induced using chloroquine where
      the efficiency of this process was sensed through changes in QD fluorescence. We
      found that increasing concentrations of pentablock copolymer and DNA led to
      quenching of QD fluorescence, while chloroquine alone had no measurable effect.
      The mechanism of quenching was elucidated by modeling the process as the
      combination of static and dynamic quenching from the pentablock copolymer and
      DNA, as well as self-quenching due the bridging of QDs. Tertiary amine
      homopolymers were also used to study the effect of chain length on quenching.
      Overall, these QDs were found to be highly effective at monitoring the
      dissociation of pentablock copolymer/DNA polyplexes in vitro and may have
      potential for studying the release of DNA within cells.

PMID- 21190374
TI  - Plasmonic interaction between overlapping nanowires.
AB  - The plasmonic interaction between overlapping nanowires with and without
      structure singularities is studied analytically and numerically. A conformal
      transformation approach is adopted to predict analytically the optical response
      of overlapping nanowires in the quasi-static limit. Surface plasmon excitations
      are shown to exhibit a lower bound cutoff frequency, which blue-shifts when the
      overlap distance increases. Between this cutoff and the surface plasmon
      frequencies, overlapping nanowires are capable of a strong and broad-band
      harvesting of light. This band gap feature is shown to be robust to radiative
      losses and to the bluntness of the structure singularities. Hence, the light
      harvesting performance of overlapping nanowires would not be damaged by
      nanofabrication imperfections. These remarkable features might be beneficial to
      the realization of plasmonic band gap filters.

PMID- 21190375
TI  - Temporal resolution in electrochemical imaging on single PC12 cells using
      amperometry and voltammetry at microelectrode arrays.
AB  - Carbon-fiber-microelectrode arrays (MEAs) have been utilized to electrochemically
      image neurochemical secretion from individual pheochromocytoma (PC12) cells.
      Dopamine release events were electrochemically monitored from seven different
      locations on single PC12 cells using alternately constant-potential amperometry
      and fast-scan cyclic voltammetry (FSCV). Cyclic voltammetry, when compared to
      amperometry, can provide excellent chemical resolution; however, spatial and
      temporal resolution are both compromised. The spatial and temporal resolution of
      these two methods have been quantitatively compared and the differences explained
      using models of molecular diffusion at the nanogap between the electrode and the
      cell. A numerical simulation of the molecular flux reveals that the diffusion of
      dopamine molecules and electrochemical reactions both play important roles in the
      temporal resolution of electrochemical imaging. The simulation also reveals that
      the diffusion and electrode potential cause the differences in signal crosstalk
      between electrodes when comparing amperometry and FSCV.

PMID- 21190376
TI  - Poisson-distributed electron-transfer dynamics from single quantum dots to C60
      molecules.
AB  - Functional quantum dot (QD)-based nanostructures are often constructed through
      the self-assembly of QDs with binding partners (molecules or other
      nanoparticles), a process that leads to a statistical distribution of the number
      of binding partners. Using single QD fluorescence spectroscopy, we probe this
      distribution and its effect on the function (electron-transfer dynamics) in QD
      C60 complexes. Ensemble-averaged transient absorption and fluorescence decay as
      well as single QD fluorescence decay measurements show that the QD exciton
      emission was quenched by electron transfer from the QD to C60 molecules and the
      electron-transfer rate increases with the C60-to-QD ratio. The electron-transfer
      rate of single QD-C60 complexes fluctuates with time and varies among different
      QDs. The standard deviation increases linearly with the average of electron
      transfer rates of single QD-C60 complexes, and the distributions of both
      quantities obey Poisson statistics. The observed distributions of single QD-C60
      complexes and ensemble-averaged fluorescence decay kinetics can be described by a
      model that assumes a Poisson distribution of the number of adsorbed C60 molecules
      per QD. Our findings suggest that, in self-assembled QD nanostructures, the
      statistical distribution of the number of adsorbed partners can dominate the
      distributions of the averages and standard deviation of their interfacial
      dynamical properties.

PMID- 21190377
TI  - Structures of vanadium(III)-ethylenediamine-N,N'-diacetato-N,N'-di-3-propionato
      complexes. Critical role of ppi-dpi donation in determining the coordination
      number.
AB  - Li[V(eddadp)].3H(2)O (1a) and Cs[V(eddadp)].2H(2)O (1b) were characterized by X
      ray crystallography. 1a crystallizes in the monoclinic space group Cc with a =
      11.467(7) A, b = 13.398(8) A, c = 12.529(8) A, beta = 114.85(4) degrees ; V =
      1746.7(2) A(3), and Z = 4; 1b crystallizes in the monoclinic space group P2(1)/n
      with a = 10.265(5) A, b = 11.673(6) A, c = 15.507(8) A, beta = 104.29(2) degrees
      , V = 1800.6(2) A(3), and Z = 4. The solution structure of 1 has been ascertained
      to be predominantly six-coordinated with a hexadentate eddadp which is based on a
      comparison of the electronic and Raman spectra of aqueous solutions of 1 with
      those in the solid state.

PMID- 21190378
TI  - Nanofibrillation of wood pulp using a high-speed blender.
AB  - We report the successful use of a high-speed blender in nanofibrillating never
      dried pulp to cellulose nanofibers (CNFs) with a uniform diameter of 15-20 nm.
      Pulp treated for 30 min in a blender showed the same degree of fibrillation with
      less damage to the CNF compared with that treated in a grinder. Observing the
      process of nanofibrillation clarified that the straw-like pulp was fibrillated in
      a very characteristic way, by forming many "balloon-like structures". As the
      balloons extended to the edges, the fibrils were rapidly individualized. However,
      the pulp fragments with ripped cell walls were split into finer fragments and
      gradually disintegrated into nanofibers. Changing the agitation speed and pulp
      concentration during the treatment revealed that the pulp concentration of 0.7 wt
      % at 37,000 rpm was the optimum fibrillation condition in this blender method.
      Through treatments in various NaCl solutions, the effect of the surface charge of
      CNF on the fibrillation was studied from the viewpoint of colloidal surface
      physics. It was found that repulsion due to the electric double layer of the CNF
      surface may play a critical role in the occurrence of fibrillation.

PMID- 21190379
TI  - On understanding stacking fault formation in ice.
AB  - Despite dedicated efforts aimed at revealing possible molecular structures of the
      ice defects associated with stacking faults in ice (I), these molecular
      arrangements have remained a puzzle. Here we demonstrate how the reorganization
      of water molecules on different faces of ice (I) can facilitate formation of
      stacking faults within a crystal. We show that a pair of point defects can
      manifest a particular combination of coupled five- and eight-membered rings (5-8
      rings). These structural motifs can facilitate a shift in layers within an ice
      (I) crystal, thereby inducing stacking faults. Furthermore, the presence of
      molecular solutes such as methane at the ice interface appears to trigger the
      formation of coupled 5-8 rings. The observation of such coupled 5-8 ring defects
      provides insights into the possible molecular mechanisms of stacking fault
      formation in ice (I) and has implications for ice crystal growth phenomenology
      and the consequent physical and chemical properties of ice.

PMID- 21190380
TI  - Purification of alkylamides from Echinacea angustifolia (DC.) Hell. Roots by high
      speed countercurrent chromatography.
AB  - High-speed countercurrent chromatography (HSCCC) was used for the separation of
      alkylamides from the roots of Echinacea angustifolia (DC.) Hell. For this
      purpose, the alkylamides were extracted with hexane and subjected to
      semipreparative HSCCC using a two-phase solvent system consisting of n-hexane,
      ethyl acetate, methanol, and water (4:1:2:1). The lower aqueous phase was used as
      the mobile phase at a flow rate of 3 mL/min and a rotary speed of 1000 rpm. This
      procedure led to the isolation of four pure alkylamides, that is, dodeca
      2E,4E,8Z,10E/Z-tetraenoic acid isobutylamide (38.9 mg, 97% purity), dodeca
      2E,4E,8Z-trienoic acid isobutylamide (4.4 mg, 92% purity), dodeca-2E,4E-dienoic
      acid isobutylamide (3.2 mg, 99% purity), and dodeca-2E,4E-dienoic acid 2
      methylbutylamide (0.3 mg, 92% purity). The identity and purity of the isolated
      alkylamides were confirmed by LC-ESI-MS and (1)H NMR and (13)C NMR data. To the
      best of the authors' knowledge, this is the first report of dodeca-2E,4E-dienoic
      acid 2-methylbutylamide in E. angustifolia roots.

PMID- 21190381
TI  - Biodegradation and mineralization of metolachlor and alachlor by Candida
      xestobii.
AB  - Metolachlor (2-chloro-6'-ethyl-N-(2-methoxy-1-methylethyl)aceto-o-toluidide) is a
      pre-emergent chloroacetanilide herbicide used to control broadleaf and annual
      grassy weeds in a variety of crops. The S enantiomer, S-metolachlor, is the most
      effective form for weed control. Although the degradation of metolachlor in soils
      is thought to occur primarily by microbial activity, little is known about the
      microorganisms that carry out this process and the mechanisms by which this
      occurs. This study examined a silty-clay soil (a Luvisol) from Spain, with 10 and
      2 year histories of metolachlor and S-metolachlor applications, respectively, for
      microorganisms that had the ability to degrade this herbicide. Tis paper reports
      the isolation and characterization of pure cultures of Candida xestobii and
      Bacillus simplex that have the ability to use metolachlor as a sole source of
      carbon for growth. Species assignment was confirmed by morphological and
      biochemical criteria and by sequence analysis of 18S and 16S rRNA, respectively.
      High-performance liquid chromatography (HPLC) and liquid chromatography-mass
      spectrometry (LC-MS) analyses indicated that C. xestobii degraded 60% of the
      added metolachlor after 4 days of growth and converted up to 25% of the compound
      into CO(2) after 10 days. In contrast, B. simplex biodegraded 30% of metolachlor
      following 5 days of growth in minimal medium. In contrast, moreover, the yeast
      degraded other acetanilide compounds and 80% of acetochlor (2-chloro-N
      ethoxymethyl-6'-ethylaceto-o-toluidide) and alachlor (2-chloro-2',6'-diethyl-N
      methoxymethylacetanilide) were degraded after 15 and 41 h of growth,
      respectively. The results of these studies indicate that microorganisms
      comprising two main branches of the tree of life have acquired the ability to
      degrade the same novel chlorinated herbicide that has been recently added to the
      biosphere.

PMID- 21190382
TI  - A-CD estrogens. I. Substituent effects, hormone potency, and receptor subtype
      selectivity in a new family of flexible estrogenic compounds.
AB  - Long-term use of estrogen supplements by women leads to an increased risk of
      breast and uterine cancers. Possible mechanisms include metabolism of estradiol
      and compounds related to tumor-initiating quinones, and ligand-induced activation
      of the estrogen receptors ERalpha and ERbeta which can cause cancer cell
      proliferation, depending on the ratio of receptors present. One therapeutic goal
      would be to create a spectrum of compounds of variable potency for ERalpha and
      ERbeta, which are resistant to quinone formation, and to determine an optimum
      point in this spectrum. We describe the synthesis, modeling, binding affinities,
      hormone potency, and a measure of quinone formation for a new family of A-CD
      estrogens, where the A-C bond is formed by ring coupling. Some substituents on
      the A-ring increase hormone potency, and one compound is much less quinone
      forming than estradiol. These compounds span a wide range of receptor subtype
      selectivities and may be useful in hormone replacement therapy.

PMID- 21190383
TI  - Halide and nitrite recognizing hexanuclear metallacycle copper(II) pyrazolates.
AB  - Halide-centered hexanuclear, anionic copper(II) pyrazolate complexes [trans
      Cu(6)((3,5-CF(3))(2)pz)(6)(OH)(6)X](-), X = Cl, Br, I are isolated in a good
      yield from the redox reaction of the trinuclear copper(I) pyrazolate complex [MU
      Cu(3)((3,5-CF(3))(2)pz)(3)] with a halide source such as PPh(3)AuCl or [Bu(4)N]X,
      X = Cl, Br, or I, in air. X-ray structures of the anion-centered hexanuclear
      complexes show that the six copper atoms are bridged by bis(3,5
      trifluoromethyl)pyrazolate and hydroxyl ligands above and below the six copper
      atom plane. The anions are located at the center of the cavity and weakly bound
      to the six copper atoms in a MU(6)-arrangement, Cu-X = ~3.1 A. A nitrite-centered
      hexanuclear copper(II) pyrazolate complex [trans-Cu(6)((3,5
      CF(3))(2)pz)(6)(OH)(6)(NO(2))](-) was obtained when a solution of [PPN]NO(2) in
      CH(3)CN was added dropwise to the trinuclear copper(I) pyrazolate complex [MU
      Cu(3)((3,5-CF(3))(2)pz)(3)] dissolved in CH(3)CN, in air. Blue crystals are
      produced by slow evaporation of the acetonitrile solvent. The X-ray structure of
      [PPN][trans-Cu(6)((3,5-CF(3))(2)pz)(6)(OH)(6)(NO(2))] complex shows the nitrite
      anion sits in the hexanuclear cavity and is perpendicular to the copper plane
      with a O-N-O angle of 118.3(7) degrees . The (19)F and (1)H NMR of the pyrazolate
      ring atoms are sensitive to the anion present in the ring. Anion exchange of the
      NO(2)(-) by Cl(-) can be observed easily by (1)H NMR.

PMID- 21190384
TI  - Total synthesis of phorboxazole A via de novo oxazole formation: convergent total
      synthesis.
AB  - The phorboxazoles are mixed non-ribosomal peptide synthase/polyketide synthase
      biosynthetic products that embody polyketide domains joined via two serine
      derived oxazole moieties. Total syntheses of phorboxazole A and analogues have
      been developed that rely upon the convergent coupling of three fragments via
      biomimetically inspired de novo oxazole formation. First, the macrolide
      containing domain of phorboxazole A was assembled from C3-C17 and C18-C30
      building blocks via formation of the C16-C18 oxazole, followed by macrolide ring
      closure involving an intramolecular Still-Genarri olefination at C2-C3.
      Alternatively, a ring-closing metathesis process was optimized to deliver the
      natural product's (2Z)-acrylate with remarkable geometrical selectivity. The C31
      C46 side-chain domain was then appended to the macrolide by a second serine amide
      derived oxazole assembly. Minimal deprotection then afforded phorboxazole A. This
      generally effective strategy was then dramatically abbreviated by employing a
      total synthesis approach wherein both of the natural product's oxazole moieties
      were installed simultaneously. A key bis-amide precursor to the bis-oxazole was
      formed in a chemoselective one-pot, bis-amidation sequence without the use of
      amino or carboxyl protecting groups. Thereafter, both oxazoles were formed from
      the key C18 and C31 bis-N-(1-hydroxyalkan-2-yl)amide in a simultaneous fashion,
      involving oxidation-cyclodehydrations. This synthetic strategy provides a total
      synthesis of phorboxazole A in 18% yield over nine steps from C3-C17 and C18-C30
      synthetic fragments. It illustrates the utility of a synthetic design to form a
      mixed non-ribosomal peptide synthase/polyketide synthase biosynthetic product
      based upon biomimetic oxazole formation initiated by amide bond formation to join
      synthetic building blocks.

PMID- 21190385
TI  - Total synthesis of phorboxazole A via de novo oxazole formation: strategy and
      component assembly.
AB  - The phorboxazole natural products are among the most potent inhibitors of cancer
      cell division, but they are essentially unavailable from natural sources at
      present. Laboratory syntheses based upon tri-component fragment coupling
      strategies have been developed that provide phorboxazole A and analogues in a
      reliable manner and with unprecedented efficiency. This has been orchestrated to
      occur via the sequential or simultaneous formation of both of the natural
      product's oxazole moieties from two serine-derived amides, involving oxidation
      cyclodehydrations. The optimized preparation of three pre-assembled components,
      representing carbons 3-17, 18-30, and 31-46, has been developed. This article
      details the design and syntheses of these three essential building blocks. The
      convergent coupling approach is designed to facilitate the incorporation of
      structural changes within each component to generate unnatural analogues,
      targeting those with enhanced therapeutic potential and efficacy.

PMID- 21190386
TI  - Quantifying the stress relaxation modulus of polymer thin films via thermal
      wrinkling.
AB  - The viscoelastic properties of polymer thin films can have a significant impact
      on the performance in many small-scale devices. In this work, we use a phenomenon
      based on a thermally induced instability, termed thermal wrinkling, to measure
      viscoelastic properties of polystyrene films as a function of geometric
      confinement via changes in film thickness. With application of the appropriate
      buckling mechanics model for incompressible and geometrically confined films, we
      estimate the stress-relaxation modulus of polystyrene films by measuring the time
      evolved wrinkle wavelength at fixed annealing temperatures. Specifically, we use
      time-temperature superposition to shift the stress relaxation curves and generate
      a modulus master curve for polystyrene films investigated here. On the basis of
      this master curve, we are able to identify the rubbery plateau, terminal
      relaxation time, and viscous flow region as a function of annealing time and
      temperatures that are well-above its glass transition. Our measurement technique
      and analysis provide an alternative means to measure viscoelastic properties and
      relaxation behavior of geometrically confined polymer films.

PMID- 21190387
TI  - Unique roles of acidic amino acids in phase transformation of calcium phosphates.
AB  - Although phase transformation is suggested as a key step in biomineralization,
      the chemical scenario about how organic molecules mediate inorganic phase
      transformations is still unclear. The inhibitory effect of amino acids on
      hydroxyapatite (HAP, the main inorganic component of biological hard tissues such
      as bone and enamel) formation was concluded by the previous biomimetic modeling
      based upon direct solution crystallization. Here we demonstrate that acidic amino
      acids, Asp and Glu, could promote HAP crystallization from its precursor crystal,
      brushite (DCPD). However, such a promotion effect could not be observed when the
      nonacidic amino acids were applied in the transformation-based HAP formation. We
      found that the specific modification of acidic amino acid on crystal-solution
      interfaces played a key role in the phase transition. The distinct properties
      between DCPD and HAP in the solution resulted in an interfacial energy barrier to
      suppress the spontaneous formation of HAP phase on DCPD phase. Different from the
      other amino acids, the carboxylate-rich amino acids, Asp and Glu, could modify
      the interfacial characteristics of these two calcium phosphate crystals to make
      them similar to each other. The experiments confirmed that the involvement of Asp
      or Glu reduced the interfacial energy barrier between DCPD and HAP, leading to a
      trigger effect on the phase transformation. An in-depth understanding about the
      unique roles of acidic amino acids may contribute to understanding phase
      transformation controls druing biomineralization.

PMID- 21190389
TI  - Structure-reactivity relationship of piperidine nitroxide: electrochemical, ESR
      and computational studies.
AB  - We have synthesized several nitroxides with different substituents which vary the
      steric and electronic environment around the N-O moiety and have systematically
      investigated the role of substituents on the stability of the radicals. Our
      results demonstrated the reactivity toward ascorbate correlates with the redox
      potential of the derivatives. Furthermore, ab initio calculations also indicated
      a correlation between the reduction rate and the computed singly occupied
      molecular orbital-lowest unoccupied molecular orbital energy gap, but not with
      solvent accessible surface area of the N-O moiety, supporting the experimental
      results and suggesting that the electronic factors largely determine the
      radicals' stability. Hence, it is possible to perform virtual screening of
      nitroxides to optimize their stability, which can help to rationally design novel
      nitroxides for their potential use in vivo.

PMID- 21190388
TI  - Manifestations of native topology in the denatured state ensemble of
      Rhodopseudomonas palustris cytochrome c'.
AB  - To provide insight into the role of local sequence in the nonrandom coil behavior
      of the denatured state, we have extended our measurements of histidine-heme loop
      formation equilibria for cytochrome c' to 6 M guanidine hydrochloride. We observe
      that there is some reduction in the scatter about the best fit line of loop
      stability versus loop size data in 6 M versus 3 M guanidine hydrochloride, but
      the scatter is not eliminated. The scaling exponent, nu(3), of 2.5 +/- 0.2 is
      also similar to that found previously in 3 M guanidine hydrochloride (2.6 +/-
      0.3). Rates of histidine-heme loop breakage in the denatured state of cytochrome
      c' show that some histidine-heme loops are significantly more persistent than
      others at both 3 and 6 M guanidine hydrochloride. Rates of histidine-heme loop
      formation more closely approximate random coil behavior. This observation
      indicates that heterogeneity in the denatured state ensemble results mainly from
      contact persistence. When mapped onto the structure of cytochrome c', the
      histidine-heme loops with slow breakage rates coincide with chain reversals
      between helices 1 and 2 and between helices 2 and 3. Molecular dynamics
      simulations of the unfolding of cytochrome c' at 498 K show that these reverse
      turns persist in the unfolded state. Thus, these portions of the primary
      structure of cytochrome c' set up the topology of cytochrome c' in the denatured
      state, predisposing the protein to fold efficiently to its native structure.

PMID- 21190390
TI  - Development of Pd/C-catalyzed cyanation of aryl halides.
AB  - A practical method for palladium-catalyzed cyanation of aryl halides using Pd/C
      is described. The new method can be applied to a variety of aryl bromide and
      active aryl chloride substrates to effect efficient conversions. The process
      features many advantages over existing cyanation conditions and the practical
      utility of the process has been demonstrated on scale.

PMID- 21190391
TI  - Incidence of traumatic spinal cord injury in Aragon, Spain (1972-2008).
AB  - Long-term incidence studies are required to identify high-risk groups, establish
      trends, and forecast needs, and thus contribute to health care planning in spinal
      cord injury (SCI). This study aimed to determine the incidence of traumatic SCI
      over a 36-year period in Aragon, Spain, and compare rates with other published
      European estimates. Hospital records from the Servet Hospital, the only
      specialized SCI unit in the region, of a retrospective cohort with traumatic SCI
      between January 1972 and December 2008 were reviewed. Specification of SCI
      patient demographics, injury causes, and related factors was achieved by
      utilizing medical records available for inpatients, hospital archives, and
      central databases. A total of 540 cases were reported over the 36-year study
      period (79% were male). The age- and sex-adjusted incidence rate was 15.5 per
      million population (18.8 for males and 4.9 for females). Two incidence peaks were
      suggested, in the 20- to 29-year and 60- to 69-year age groups. Traffic accidents
      and falls were the main causes of injury. The highest peak occurs in young
      adults, mainly caused by traffic accidents. The majority of the lesions were at
      cervical or thoracic level, and ASIA grade A was most frequently observed. The
      proportion of SCI cases in persons older than 60 years, mostly due to falls, is
      increasing. The age-adjusted incidence rates found for the region of Aragon in
      Spain fall within the range of other published European estimates. Comparative
      epidemiological features for 2001-2008 suggest that there is room for prevention.

PMID- 21190392
TI  - Asthma prescription patterns for children: can GPs do better?
AB  - BACKGROUND: Assessing prescription patterns of asthma medication for children is
      helpful to optimize prescribing by general practitioners (GPs). The aim was to
      explore prescription patterns in children with physician-diagnosed asthma and its
      determinants in general practice. METHODS: We used the Second Dutch National
      Survey of General Practice (DNSGP-2) with children aged 0-17 years registered in
      87 general practices. All children with at least one asthma prescription were
      included (n = 2993). Prescription rates and prescription of continuous (>=3
      prescriptions/year) versus intermittent asthma medication were calculated. Data,
      including several GP characteristics, were analysed using multivariate logistic
      regression accounting for clustering within practices. RESULTS: During one year,
      16% of the children with physician-diagnosed asthma (n = 3562) received no asthma
      medication. Of the 2993 children with asthma receiving asthma medication (on
      average 2.9 prescriptions/year), 61% received one or two prescriptions, 39%
      received three or more. Continuous medication with a bronchodilator and/or a
      corticosteroid was prescribed in 22% of these children. One out of 5 children
      receiving continuous medication was prescribed a bronchodilator only. In 7.5% of
      the prescriptions, asthma medications other than bronchodilators or
      corticosteroids were prescribed. Prescribing asthma medication varied widely
      between practices, but none of the children and GP determinants had an
      independent effect on prescribing continuous versus intermittent medication.
      CONCLUSION: In general practice, the annual number of asthma prescriptions per
      child with asthma is relatively low. One in 20 children is prescribed
      bronchodilators only continuously, indicating room for improvement. Child and GP
      characteristics cannot be used for targeting educational efforts.

PMID- 21190393
TI  - Senataxin mutations and amyotrophic lateral sclerosis.
AB  - We studied three patients with mutations in the senataxin gene (SETX). One had
      juvenile onset of ALS. The second case resembled hereditary motor neuropathy. The
      third patient had an overlap syndrome of ataxia-tremor and motor neuron disease,
      phenotypes previously associated with SETX mutations. Our patients were all
      apparently sporadic, with no other affected relative. Two relatives of patient
      no. 2 carried the SETX c.4660T > G transversion but did not manifest motor neuron
      disease, abnormal eye movements, ataxia, or tremor suggesting that genetic or
      environmental modifiers may influence expression of this SETX polymorphism.
      Relatives of patients 1 and 3 were not available for examination or SETX mutation
      screening. Mutations causing ALS4 may be more frequent and heterogeneous than
      expected. Screening for SETX mutations should be considered in patients with
      apparently sporadic juvenile-onset ALS, hereditary motor neuropathy, and overlap
      syndromes with ataxia and motor neuron disease.

PMID- 21190395
TI  - Audiogram: is there a need for change in the approach to categorize the
      degree/severity of hearing loss?

PMID- 21190394
TI  - Musical pitch and lexical tone perception with cochlear implants.
AB  - OBJECTIVE: The purpose of the present study was to test the hypothesis that
      cochlear implant (CI) users' music perception is correlated with their lexical
      tone perception, and the two types of perception share similar mechanisms in
      electric hearing. DESIGN: A lexical tone perception test and a pitch interval
      discrimination test were administered to a group of CI users and a group of
      normal-hearing (NH) listeners. SAMPLE STUDY: Nineteen adult CI users and 10 NH
      listeners who are native-Mandarin-Chinese speakers participated in the study.
      RESULT: Tone-perception performance of the CI group was, on average, 58.3%
      correct (+/- 19.78% correct), and performance of the NH group was near perfect.
      The CI group had a mean threshold of 5.66 semitones (+/- 5.57 semitones) in pitch
      discrimination as compared to the threshold of 0.44 semitone from the NH group.
      There was a strong correlation between the CI users' tone-perception performance
      and their pitch discrimination threshold (r = -0.75, p < 0.001). CONCLUSION:
      Musical and lexical pitch perceptions are strongly correlated with each other and
      they might share similar mechanisms in electric hearing.

PMID- 21190396
TI  - Stereology and ultrastructure of chronic phase axonal and cell soma pathology in
      stretch-injured central nerve fibers.
AB  - Magnetic resonance imaging (MRI) suggests that with survival after human
      traumatic brain injury (TBI), there is ongoing loss of white and grey matter from
      the injured brain during the chronic phase. However; direct quantitative
      experimental evidence in support of this observation is lacking. Using the guinea
      pig stretch-injury optic nerve model, quantitative evidence by stereology of
      damage to the optic nerve and retina was sought. Stretch injury was applied to
      the right optic nerve of 15 adult male guinea pigs. Three animals each at 1, 2,
      3, 8, or 12 weeks' survival were killed and prepared for transmission electron
      microscopy (TEM). The estimated number of intact and injured axons within bins of
      transverse diameters 0-0.5, 0.51-1.0, 1.01-1.5, 1.51-2.0, 2.01-2.5, and 2.51-3.0
      MUm in the middle segment of each injured optic nerve and from 5 control animals
      were compared across all survival time points. The estimated numbers of intact
      and pyknotic retinal ganglion cells from the same animals were also compared.
      Loss of myelinated fibers continued throughout the experimental period. The most
      rapid loss was of the largest fibers; loss of intermediate-sized fibers
      continued, but the numbers of the smallest fibers increased from 3 weeks onward.
      There was hypertrophy and proliferation of glial cells within the surrounding
      neuropil. A relatively low-grade loss of retinal ganglion cells occurred
      throughout the experiment, with about 60% remaining at 12 weeks' survival. We
      provide quantitative evidence that after traumatic axonal injury (TAI) there is a
      continuing loss of nerve fibers and their cell bodies from a CNS tract over a 3
      month post-traumatic interval.

PMID- 21190397
TI  - A preliminary investigation on the possible association between diminished copper
      availability and non-alcoholic fatty liver disease in epileptic patients treated
      with valproic acid.
AB  - BACKGROUND: Patients treated with valproic acid (VPA) present a high incidence of
      non-alcoholic fatty liver disease (NAFLD) (around 61%). Several recent studies
      suggest that low copper stores could be associated with NAFLD, and a significant
      decrease of copper availability in VPA-treated patients has been described.
      DESIGN AND METHODS: In 101 adult epileptic patients treated with valproic acid in
      monotherapy (n = 75) and polytherapy (n = 26) the copper availability was
      evaluated using the specific oxidase activity of ceruloplasmin (activity per unit
      mass of enzyme protein) and the copper/ceruloplasmin ratio. Copper deficiency was
      supposed in the cases in which this biochemical variable was smaller than the
      lower reference limit (333 U/g). RESULTS: The differences between the groups of
      patients with ceruloplasmin oxidase activity smaller or greater than 333 U/g for
      the serum levels of aminotransferases, gamma-glutamyltransferase,
      butyrylcholinesterase, cholesterol, triglycerides, and C-reactive protein, and
      the APRI and FIB-4 liver fibrosis scores were not statistically significant. Most
      patients (93%) had low APRI and FIB-4 scores, suggesting absence of significant
      liver fibrosis. CONCLUSIONS: The results obtained do not confirm the hypothesis
      of an association between diminished copper availability and NAFLD in patients
      treated with valproic acid.

PMID- 21190399
TI  - Systemic allergic contact dermatitis to fiberglass in a factory worker of wind
      turbine blades.
AB  - Fiberglass is extensively used due to its properties of thermal, acoustic and
      electrical insulation, and also to reinforce other materials such as plastics.
      Irritant contact dermatitis to fiberglass is a well established occupational
      dermatose and is due to penetration of small fragments in the cornified layer of
      the skin. On the other hand, allergic contact dermatitis (ACD) is rare and is
      more often triggered by sensitivity to the additives and resins used in the
      manufacture of fiberglass products. We report a case of ACD to fiberglass in a
      factory worker of fiberglass reinforced products.

PMID- 21190398
TI  - Craniotomy: true sham for traumatic brain injury, or a sham of a sham?
AB  - Abstract Neurological dysfunction after traumatic brain injury (TBI) is caused by
      both the primary injury and a secondary cascade of biochemical and metabolic
      events. Since TBI can be caused by a variety of mechanisms, numerous models have
      been developed to facilitate its study. The most prevalent models are controlled
      cortical impact and fluid percussion injury. Both typically use "sham"
      (craniotomy alone) animals as controls. However, the sham operation is
      objectively damaging, and we hypothesized that the craniotomy itself may cause a
      unique brain injury distinct from the impact injury. To test this hypothesis, 38
      adult female rats were assigned to one of three groups: control (anesthesia
      only); craniotomy performed by manual trephine; or craniotomy performed by
      electric dental drill. The rats were then subjected to behavioral testing,
      imaging analysis, and quantification of cortical concentrations of cytokines.
      Both craniotomy methods generate visible MRI lesions that persist for 14 days.
      The initial lesion generated by the drill technique is significantly larger than
      that generated by the trephine. Behavioral data mirrored lesion volume. For
      example, drill rats have significantly impaired sensory and motor responses
      compared to trephine or naive rats. Finally, of the seven tested cytokines, KC
      GRO and IFN-gamma showed significant increases in both craniotomy models compared
      to naive rats. We conclude that the traditional sham operation as a control
      confers profound proinflammatory, morphological, and behavioral damage, which
      confounds interpretation of conventional experimental brain injury models. Any
      experimental design incorporating "sham" procedures should distinguish among
      sham, experimentally injured, and healthy/naive animals, to help reduce
      confounding factors.

PMID- 21190400
TI  - Technology-based interventions targeting substance use disorders and related
      issues: an editorial.

PMID- 21190401
TI  - A review of computer-based interventions used in the assessment, treatment, and
      research of drug addiction.
AB  - Computer-based interventions are cost-efficient methods that may result in
      greater access to drug addiction treatment. We review recent findings from our
      laboratory where computer-based interventions have produced outcomes that are
      comparable to therapist-delivered interventions. We also examine how computer
      based interventions targeting substance abuse disorders relate to cognitive
      functioning. This review will suggest that not only are computer-based
      interventions cost-efficient and accessible but that they are also effective
      methods for the motivation, engagement, and treatment of drug-dependent
      individuals. Moreover, computer-based interventions are compatible with a
      recently proposed biological mechanism implicated as the basis for drug
      addiction.

PMID- 21190402
TI  - Contingency management in the 21st century: technological innovations to promote
      smoking cessation.
AB  - Information technology represents an excellent medium to deliver contingencies of
      reinforcement to change behavior. Recently, we have linked the Internet with a
      science-based, behavioral treatment for cigarette smoking: abstinence
      reinforcement therapy. Under abstinence reinforcement interventions, incentives
      are provided for objective evidence of abstinence. Several studies suggest that
      the intervention is effective in initiating abstinence. The intervention
      addresses limitations (access, cost, sustainability, and dissemination potential)
      inherent in traditional abstinence reinforcement delivery models. It can also be
      applied to vulnerable, at-risk populations, and to other behavior to promote
      health. Information technologies offer unprecedented and rapidly expanding
      opportunities to facilitate behavior change.

PMID- 21190403
TI  - Cognitive function and treatment response in a randomized clinical trial of
      computer-based training in cognitive-behavioral therapy.
AB  - Cognitive-behavioral therapy (CBT), because of its comparatively high level of
      cognitive demand, is likely to be challenging for substance users with
      limitations in cognitive function. However, it is not known whether computer
      assisted versions of CBT will be particularly helpful (e.g., allowing
      individualized pace and repetition) or difficult (e.g., via complexity of
      computerized delivery) for such patients. In this secondary analysis of data
      collected from a randomized clinical trial evaluating computer-assisted CBT, four
      aspects of cognitive functioning were evaluated among 77 participants. Those with
      higher levels of risk taking completed fewer sessions and homework assignments
      and had poorer substance use outcomes.

PMID- 21190404
TI  - Preventing substance use among Black and Hispanic adolescent girls: results from
      a computer-delivered, mother-daughter intervention approach.
AB  - This 2008 study involved 546 Black and Hispanic American adolescent girls and
      their mothers from New York, New Jersey, and Connecticut. Participants provided
      self-report data. Analysis of covariance indicated that the experimental
      intervention reduced risk factors, improved protective factors, and lowered
      girls' alcohol use and their future intentions to use substances. The study
      supports the value of computer-based and gender-specific interventions that
      involve girls and their mothers. Future work needs to replicate and strengthen
      study results.

PMID- 21190405
TI  - Computer-assisted HIV prevention for youth with substance use disorders.
AB  - We developed an interactive, customizable, Web-based program focused on the
      prevention of HIV, sexually transmitted infections, and hepatitis among youth.
      Results from a randomized, controlled trial with youth in treatment for substance
      use demonstrated that this Web-based tool, when provided as an adjunct to an
      educator-delivered prevention intervention, increased accurate prevention
      knowledge, increased intentions to carefully choose partners, and was perceived
      as significantly more useful relative to the educator-delivered intervention when
      provided alone. Results suggest this Web-based program may be effective and
      engaging and may increase the adoption of effective HIV and disease prevention
      science for youth. Limitations are discussed.

PMID- 21190406
TI  - A series of studies examining Internet treatment of obesity to inform Internet
      interventions for substance use and misuse.
AB  - The feasibility and efficacy of Internet treatment programs for overweight and
      obese people have been demonstrated in a series of randomized trials. Initial
      studies examined various approaches to Internet behavioral treatment. Other
      studies have examined delivery of group behavioral counseling using Internet chat
      rooms, using the Internet for long-term maintenance of weight loss, and enhancing
      motivation in Internet programs. These interventions have produced weight losses
      of 4-7 kg over 6 months to 1 year when support via e-mail, automated messages, or
      chat rooms is provided. Outcomes and lessons learned with application to the
      treatment of substance use and misuse are provided.

PMID- 21190407
TI  - Connecting to young adults: an online social network survey of beliefs and
      attitudes associated with prescription opioid misuse among college students.
AB  - A survey of motives and attitudes associated with patterns of nonmedical
      prescription opioid medication use among college students was conducted on
      Facebook, a popular online social networking Web site. Response metrics for a 2
      week random advertisement post, targeting students who had misused prescription
      medications, surpassed typical benchmarks for online marketing campaigns and
      yielded 527 valid surveys. Respondent characteristics, substance use patterns,
      and use motives were consistent with other surveys of prescription opioid use
      among college populations. Results support the potential of online social
      networks to serve as powerful vehicles to connect with college-aged populations
      about their drug use. Limitations of the study are noted.

PMID- 21190408
TI  - The potential for technology in brief interventions for substance use, and during
      session prediction of computer-delivered brief intervention response.
AB  - We first provide an overview of the potential of technology in the area of brief
      interventions for substance use and describe recent projects from our lab that
      are illustrative of that potential. Second, we present data from a study of
      during-session predictors of brief intervention response. In a sample of
      postpartum women (N = 39), several variables showed promise as predictors of
      later drug use, and a brief index derived from them predicted abstinence with a
      sensitivity of .7 and a specificity of .89. This promising approach and initial
      study findings support the importance of future research in this area.

PMID- 21190409
TI  - Using the methods of ecological momentary assessment in substance dependence
      research--smoking cessation as a case study.
AB  - Ecological momentary assessment (EMA) is the name applied to any of a range of
      research methodologies that aim to assess participants in near real time as they
      go about their regular day-to-day activities. Such methods have particular
      utility for studying drug use and drug dependence. Using the area of nicotine
      dependence as a case study, this review highlights how EMA can be used to build
      upon the findings from more traditional research methods to enhance our
      understanding of drug use. Particular attention is given to the role that
      advances in technology have played in the adoption of EMA in drug dependence
      research.

PMID- 21190411
TI  - Application of technology in the prevention and treatment of substance use
      disorders and related problems: opportunities and challenges.

PMID- 21190413
TI  - Variation in SNPs of the IL7Ra gene is associated with multiple sclerosis in the
      Iranian population.
AB  - Interleukin-7 receptor-alpha gene (IL7Ra) is a member of the type I cytokine
      receptor family located on 5p13 human chromosome. Some evidence associates
      multiple sclerosis and single nucleotide polymorphisms in the promoter and exonic
      region of IL7Ra gene. In an attempt to clarify this association, the frequency of
      3 SNPs located in the promoter and 1 SNP located in the 6th exon of IL7Ra gene
      were analyzed in a population of 100 Iranian MS patients as well as 100 controls.
      Restriction enzyme digestion and a designed mismatch PCR-RFLP strategy were used
      for the SNP genotyping of our study groups. Considering allele, genotype and
      haplotype frequencies, no significant association was observed between MS and
      IL7Ra polymorphisms. Meanwhile, a significant difference was detected between
      control and primary progressive MS patients considering promoter SNPrs11567685
      marker frequency. Also, a significant difference was detected considering exonic
      SNPrs6897932 for secondary progressive MS patients. Our analysis indicates that
      GCAC and GTAT haplotypes are less common in SP and PP MS groups, respectively.
      These differences support the concept that clinical phenotypes may have different
      etiologies and, therefore, require different therapy strategies.

PMID- 21190410
TI  - Explicating an evidence-based, theoretically informed, mobile technology-based
      system to improve outcomes for people in recovery for alcohol dependence.
AB  - Post-treatment relapse to uncontrolled alcohol use is common. Currently available
      communication technology can use existing models for relapse prevention to cost
      effectively improve long-term relapse prevention. This paper describes: (1)
      research-based elements of alcohol consumption-related relapse prevention and how
      they can be encompassed in self-determination theory (SDT) and Marlatt's
      cognitive behavioral relapse prevention model, (2) how technology could help
      address the needs of people seeking recovery, (3) a technology-based prototype,
      organized around sexual transmitted disease and Marlatt's model, and (4) how we
      are testing a system based on the ideas in this article and related ethical and
      operational considerations.

PMID- 21190414
TI  - The value of combined cervical length measurement and fetal fibronectin testing
      to predict spontaneous preterm birth in asymptomatic high-risk women.
AB  - OBJECTIVES: To determine the value of the combined use of fetal fibronectin (fFN)
      testing and transvaginal ultrasound measurement of cervical length (CL) for
      prediction of preterm birth (PTB) in asymptomatic high-risk women. METHODS: One
      hundred and forty-seven asymptomatic women at high-risk of PTB were referred to
      specialist antenatal clinics and underwent CL and fFN testing over a 12-month
      period. Women had both tests undertaken between 22(+0) and 30(+0) weeks'
      gestation, on one or more occasions. RESULTS: In those who labored spontaneously
      (n = 132), positive fFN and CL <= 25 mm was associated with a 53% risk of PTB at 
      < 37(+0) weeks' gestation, compared to a 10% risk in those with a negative fFN
      and CL  >  25 mm. With a known CL, the addition of positive fFN yielded
      significant hazard ratios regardless of CL (CL  >  25 mm-HR 2.78, CL  <= 25 mm-HR
      3.14, p < 0.05). The hazard ratios were insignificant when CL results were added
      to a known fFN. CONCLUSIONS: In high-risk asymptomatic women, fFN may be used as
      a primary screening tool with CL measurement being reserved for those with a
      positive fFN result. Further prospective studies are needed to confirm our
      findings.

PMID- 21190415
TI  - A simultaneous comparison of four neonatal pain scales in clinical settings.
AB  - OBJECTIVE: To evaluate the usefulness of four neonatal pain scales (DAN, NIPS,
      PIPP, and NPAS) in describing newborn's response to a painful event in clinical
      settings. METHODS: Prospective observational study at university-affiliated
      neonatal unit. Three hundred-sixty newborns were observed during venepuncture and
      heel lancing as a part of routine blood workout. Values of pain scales were
      determined in three time frames (start of procedure - T0, maximal response - T1,
      end of procedure - T2). RESULTS: In T0 versus T1 time frame, a sharp increase of
      percentage was observed in all pain scales independently of procedure with high
      statistical significance (P ~ 0.00). NIPS showed the highest (venepuncture 742%;
      heel lancing 1472%) and PIPP the lowest increase (venepuncture 303%; heel lancing
      510%). In T1 versus T2 time frame, for venepuncture NIPS showed the highest (49%)
      and PIPP the lowest (38%) percentage of decrease, whereas for heel lancing PIPP
      had the highest (28%) and NIPS the lowest (20%) one. All pain scales showed
      significant individual and overall variability (CV > 30%). PIPP had the lowest
      (42.7 + 14.3) and NIPS the highest (103.8 + 91.3) overall coefficient of
      variation. DAN's confidence parameters were the most uniform ones (se 1.0, sp
      0.93, ppv 0.93, npv 1.0), whereas PIPP's confidence parameters were the highest
      while measuring high intensity pain (se 0.94, sp 1.0, ppv 1.0, npv 0.94).
      CONCLUSION: DAN is a pain scale convenient for the use in clinical settings,
      especially if a fine distinction of magnitude of the present pain is not needed,
      whereas PIPP can be used if adequate equipment is available.

PMID- 21190416
TI  - Assessing osteoporosis risk factors in Spanish menopausal women.
AB  - OBJECTIVES: (1) To assess the prevalence of osteoporosis risk factors in Spanish
      menopausal women; (2) to detect medical and lifestyle risk factor differences
      between perimenopausal and postmenopausal women; (3) and to identify the main
      factors responsible for osteoporosis. METHODS: Cross-sectional descriptive study
      encompassing women aged 45-65 across Spain. The study population sample was
      collected through random sampling and a total of 10,514 women were included.
      Socio-demographic, medical history, and lifestyle data were assessed. RESULTS:
      The prevalence of osteoporosis risk factors was 67.6%. The most common risk
      factors were physical inactivity (53.6%), use of medication related to
      osteoporosis risk (45.9%), and low calcium intake (30.1%). There were
      statistically significant differences between peri- and postmenopausal women in
      terms of smoking status, alcohol intake, personal history, poor dairy product
      intake, and medication use that could increase risk. Logistic regression analysis
      showed that osteoporosis was significantly associated with age, family history,
      age at onset of menopause, Kupperman Index, prolonged immobilization, weight
      loss, and other diseases that increase the probability of developing
      osteoporosis. CONCLUSIONS: A high prevalence of women taking osteoporosis risk
      related medication was observed in our study. There was correlation between the
      menopausal symptoms' degree of severity and the risk of suffering from
      osteoporosis.

PMID- 21190417
TI  - Low gestational weight gain improves infant and maternal pregnancy outcomes in
      overweight and obese Korean women with gestational diabetes mellitus.
AB  - OBJECTIVE: The aim of the study was to retrospectively assess what was the
      optimal gestational weight gain to have better maternal and neonatal outcomes in
      overweight and obese Korean women with gestational diabetes mellitus (GDM) who
      maintained normoglycemia throughout pregnancy by dietary modification, exercise,
      and/or insulin treatment. STUDY DESIGN: We performed a hospital-based study of
      215 GDM women with prepregnancy BMI >= 25 kg/m(2). Body weight, glucose
      homeostasis, lipid profiles, insulin treatment, and maternal outcomes were
      collected as predictors of neonatal birth weight. We divided the subjects into
      three groups according to modified Institute of Medicine (IOM) guidelines for
      weight gain during pregnancy: inadequate (n = 42), normal (n = 96), and excessive
      (n = 77) groups. RESULTS: Excessive weight gain resulted in increased macrosomia,
      HbA(1c) at delivery, and postprandial blood glucose levels, but fasting blood
      glucose levels were not significantly different among the groups. The inadequate
      weight gain group (2.4 kg weight gain during pregnancy) had better neonatal
      outcomes and better maternal glycemic control with fewer requiring insulin
      treatment. CONCLUSION: Minimal weight gain, well below IOM recommendations, and
      tight control of blood glucose levels during pregnancy with proper medical
      management and dietary modification may eliminate most of the adverse pregnancy
      outcomes experienced by obese GDM Asian women.

PMID- 21190418
TI  - Allopregnanolone, a GABAA receptor agonist, decreases gonadotropin levels in
      women. A preliminary study.
AB  - Animal studies suggest regulatory effects on the hypothalamic-pituitary-gonad
      axis by allopregnanolone, an endogenous gamma-aminobutyric acid A (GABA(A))
      receptor agonist. Elevated levels of allopregnanolone in women with hypothalamic
      amenorrhea have been seen. Isoallopregnanolone is an isomer to allopregnanolone,
      but without GABA(A) receptor effects. The purpose of this study was to
      investigate effects of allopregnanolone and isoallopregnanolone on gonadotropin
      levels in healthy women of fertile age. Ten women were given allopregnanolone and
      five women isoallopregnanolone intravenously in follicular phase. Repeated blood
      samples were drawn during the test day. Main outcomes were changes in serum
      levels of follicle-stimulating hormone (FSH), luteinising hormone (LH),
      oestradiol, and progesterone. Serum-FSH decreased between 5 and 105 min after the
      allopregnanolone injection (F(16,144)=2.18, p=0.008). Serum-LH was reduced
      between 5 and 35 min following the allopregnanolone injection (F(16,144)=2.63,
      p=0.001). Serum-oestradiol and -progesterone were not significantly changed after
      allopregnanolone injections. No effect on gonadotropin levels were seen after
      administration of isoallopregnanolone. Allopregnanolone reduces FSH and LH levels
      in women and the effect might be mediated via a specific GABA(A) receptor
      activation since isoallopregnanolone lacked this effect. Although the number of
      women was small, the results suggest a regulatory mechanism on the hypothalamic
      pituitary-gonadal axis by allopregnanolon.

PMID- 21190419
TI  - Does nuchal translucency thickness in the first trimester predict GDM onset
      during pregnancy?
AB  - BACKGROUND AND AIMS: This study was planned to evaluate whether increased nuchal
      translucency (NT) thickness in the first trimester of gestation can be related to
      onset of gestational diabetes mellitus (GDM) during pregnancy. METHODS: From
      January 2006 to August 2008, a group of 678 singleton pregnancies who had
      developed GDM has been selected as a study group among a total of 3966 pregnant
      women who had undergone first trimester screening for aneuploidies at 11-14 weeks
      of gestation. A group of 420 single pregnant women with physiological pregnancy
      were enrolled as control group. Both fetal structural and karyotype's anomalies
      were excluded in the two groups. NT was mesured by a Fetal Medicine Foundation
      certificated operator; GDM was diagnosed at 24-28 weeks of gestation following
      Carpenter and Coustan criteria. In the analyses of continuos variables, study and
      control group were compared by Student's t-test and Anova test. RESULTS: There
      was no significative difference (p = 0.585) between NT values in the study (mean
      = 1.56) and control group (mean = 1.54). CONCLUSIONS: NT thickness does not show
      a significative increase in those women who subsequently develop GDM. Therefore,
      NT assessment does not prove to be an useful ultrasound parameter for predicting
      GDM onset during pregnancy.

PMID- 21190420
TI  - Is sildenafil citrate affect endometrial receptivity? An immunohistochemical
      study.
AB  - The authors aimed to investigate the effect of sildenafil citrate (Sc) on
      expressions of beta(3) integrin and vascular endothelial growth factor (VEGF),
      which is taking part in endometrium receptivity in implantation window period in
      controlled ovarian hyperstimulation (COH) performed rats. In this study, Wistar
      albino female rats were used and were divided into four groups as control, COH,
      Sc, and COH + Sc groups. They were sacrificed on the third, fourth, and fifth day
      of pregnancy, uteruses were resected, and uteri sections were stained with
      immunohistochemical method and evaluated. beta(3) integrin immunoreactivity was
      most intensely observed in the endometrial glandular epithelium (GE) and stromal
      cells in the Sc group on the third day, whereas immunoreactivity was most
      intensely detected in the luminal epithelium (LE), GE, and stromal cells in the
      Sc group on the fourth day. VEGF immunoreactivity was most intensely observed in
      the endometrial LE in the Sc group on the third day, in the Sc and COH + Sc
      groups on the fourth day, and in the COH + Sc group on the fifth day. Our results
      indicated that Sc plays a role in both implantation and decidualization by
      affecting beta(3) integrin and VEGF expressions in implantation window period in
      rats.

PMID- 21190421
TI  - Effects of systemic administration of methylprednisolone on residual hearing in
      an animal model of cochlear implantation.
AB  - CONCLUSION: Delivery of intramuscular injection of methylprednisolone around the
      implantation surgery improved the hearing threshold shift induced by cochlear
      implantation. OBJECTIVES: During electroacoustic cochlear implantation surgery,
      the residual hearing is not preserved in about 15% of cases. In this study, we
      tested the effects of intramuscular administration of methylprednisolone on the
      hearing loss induced by cochlear implantation in a model of guinea pig cochlear
      implantation. METHODS: Eleven guinea pigs with normal hearing were implanted with
      a 254 MUm diameter silicone array through a cochleostomy, and the effects on
      hearing of longstanding array insertion (21 days) were assessed. Six of the
      implanted animals received intramuscular administration of methylprednisolone.
      Auditory brainstem response recordings were performed before and up to 21 days
      after the cochlear implantation. CT scans were performed in some animals 1 month
      after implantation. RESULTS: CT scans confirmed that the array was well
      positioned in tested animals. From days 3 to 21, a hearing loss of about 30 dB on
      all frequencies was observed in the implanted nontreated group. This hearing loss
      remained stable during the whole follow-up period. Compared with implanted
      nontreated animals, the hearing threshold shift decreased by 12 dB in animals
      treated with methylprednisolone.

PMID- 21190422
TI  - Electroporation therapy for T1 and T2 oral tongue cancer.
AB  - CONCLUSION: Electroporation therapy appears to be a safe treatment achieving
      excellent local tumor control and very good functional results in our study and
      it should be further clinically evaluated. OBJECTIVES: The objectives of this
      study were to assess local tumor control, survival, and effects on speech and
      eating after treatment of tongue cancer with electroporation therapy, a new local
      therapeutic modality. In this approach intracellular accumulation of a
      chemotherapeutic agent is achieved by using a locally applied electrical field.
      METHODS: Fifteen patients with primary T1 and T2 oral tongue cancer were treated
      with electroporation therapy with intratumorally administered bleomycin.
      Postoperative radiotherapy was performed when the tumor infiltration was 5 mm or
      more. The follow-up time was 24 months for the surviving patients and 20.4 months
      overall. The effects on eating and speech were assessed using the PSS-HN scale
      and voice recordings. RESULTS: No local recurrence was recorded in any patient
      during the follow-up. Three patients died, two from progressive regional disease.
      Of the 12 surviving patients, 2 patients had regional recurrence and 10 patients
      including the 5 patients treated with EPT alone were tumor-free both locally and
      regionally at the last follow-up. The functional outcome for speech and eating
      were very good.

PMID- 21190423
TI  - Genetic variation and variation in aggressiveness to native and exotic hosts
      among Brazilian populations of Ceratocystis fimbriata.
AB  - Ceratocystis fimbriata is a complex of many species that cause wilt and cankers
      on woody plants and rot of storage roots or corms of many economically important
      crops worldwide. In Brazil, C. fimbriata infects different cultivated crop plants
      that are not native to Brazil, including Gmelina arborea, Eucalyptus spp.,
      Mangifera indica (mango), Ficus carica (fig), and Colocasia esculenta (inhame).
      Phylogenetic analyses and inoculation studies were performed to test the
      hypothesis that there are host-specialized lineages of C. fimbriata in Brazil.
      The internal transcribed spacer region ribosomal DNA sequences varied greatly but
      there was little resolution of lineages based on these sequences. A portion of
      the MAT1-2 mating type gene showed less variation, and this variation
      corresponded more closely with host of origin. However, mango isolates were found
      scattered throughout the tree. Inoculation experiments on the five exotic hosts
      showed substantial variation in aggressiveness within and among pathogen
      populations. Native hosts from the same families as the exotic hosts tended to be
      less susceptible than the cultivated hosts, but there was little correlation
      between aggressiveness to the cultivated and native hosts of the same family.
      Cultivation and vegetative propagation of exotic crops may select for strains
      that are particularly aggressive on those crops.

PMID- 21190424
TI  - Models for predicting potential yield loss of wheat caused by stripe rust in the
      U.S. Pacific Northwest.
AB  - Climatic variation in the U.S. Pacific Northwest (PNW) affects epidemics of wheat
      stripe rust caused by Puccinia striiformis f. sp. tritici. Previous models only
      estimated disease severity at the flowering stage, which may not predict the
      actual yield loss. To identify weather factors correlated to stripe rust
      epidemics and develop models for predicting potential yield loss, correlation and
      regression analyses were conducted using weather parameters and historical yield
      loss data from 1993 to 2007 for winter wheat and 1995 to 2007 for spring wheat.
      Among 1,376 weather variables, 54 were correlated to yield loss of winter wheat
      and 18 to yield loss of spring wheat. Among the seasons, winter temperature
      variables were more highly correlated to wheat yield loss than the other seasons.
      The sum of daily temperatures and accumulated negative degree days of February
      were more highly correlated to winter wheat yield loss than the other monthly
      winter variables. In addition, the number of winter rainfall days was found
      correlated with yield loss. Six yield loss models were selected for each of
      winter and spring wheats based on their better correlation coefficients, time of
      weather data availability during the crop season, and better performance in
      validation tests. Compared with previous models, the new system of using a series
      of the selected models has advantages that should make it more suitable for
      forecasting and managing stripe rust in the major wheat growing areas in the U.S.
      PNW, where the weather conditions have become more favorable to stripe rust.

PMID- 21190425
TI  - Monitoring gender equity in health using gender-sensitive indicators: a cross
      national study.
AB  - BACKGROUND: As gender is known to be a major determinant of health, monitoring
      gender equity in health systems remains a vital public health priority. Focusing
      on a low-income (Peru), middle-income (Colombia), and high-income (Canada)
      country in the Americas, this study aimed to (1) identify and select gender
      sensitive health indicators and (2) assess the feasibility of measuring and
      comparing gender-sensitive health indicators among countries. METHODS: Gender
      sensitive health indicators were selected by a multidisciplinary group of experts
      from each country. The most recent gender-sensitive health measures corresponding
      to selected indicators were identified through electronic databases (CINAHL,
      PsycINFO, MEDLINE, Embase, LILACS, LIPECS, Latindex, and BIREME) and expert
      consultation. Data from population-based studies were analyzed when indicator
      information was unavailable from reports. RESULTS: Twelve of the 17 selected
      gender-sensitive health indicators were feasible to measure in at least two
      countries, and 9 of these were comparable among all countries. Indicators that
      were available were not stratified or adjusted by age, education, marital status,
      or wealth. The largest between-country difference was maternal mortality, and the
      largest gender inequity was mortality from homicides. CONCLUSIONS: This study
      shows that gender inequities in health exist in all countries, regardless of
      income level. Economic development seemed to confer advantages in the
      availability of such indicators; however, this finding was not consistent and
      needs to be further explored. Future initiatives should include identifying
      health system factors and risk factors associated with disparities as well as
      assessing the cost-effectiveness of including the routine monitoring of gender
      inequities in health.

PMID- 21190426
TI  - Some sulfonamide drugs inhibit ATPase activity of heat shock protein 90:
      investigation by docking simulation and experimental validation.
AB  - Eight selected sulfonamide drugs were investigated as inhibitors of heat shock
      protein 90 (Hsp90). The investigation included simulated docking experiments to
      fit the selected compounds within the binding pocket of Hsp90. The selected
      molecules were found to readily fit within the ATP-binding pocket of Hsp90 in low
      energy poses. The sulfonamides torsemide, sulfathiazole, and sulfadiazine were
      found to inhibit the ATPase activity of Hsp90 with IC(50) values of 1.0, 2.6, and
      1.5 MUM, respectively. Our results suggest that these well-established
      sulfonamides can be good leads for subsequent optimization into potent Hsp90
      inhibitors.

PMID- 21190427
TI  - Waxing and waning intravascular large cell lymphoma with widespread organ
      infiltration.

PMID- 21190428
TI  - Palaeontological evidence of membrane relationship in step-by-step membrane
      fusion.
AB  - Studies on membrane fusion in living cells indicate that initiation of membrane
      fusion is a transient and hard to capture process. Despite previous research,
      membrane behaviour at this point is still poorly understood. Recent
      palaeobotanical research has revealed snapshots of membrane fusion in a 15
      million-year-old fossil pinaceous cone. To reveal the membrane behaviour during
      the fusion, we conducted more observations on the same fossil material. Several
      discernible steps of membrane fusion have been fixed naturally and observed in
      the fossil material. This observation provides transmission electron microscope
      (TEM) images of the transient intermediate stage and clearly shows the
      relationship between membranes. Observing such a transient phenomenon in fossil
      material implies that the fixing was most likely accomplished quickly by a
      natural process. The mechanism behind this phenomenon is clearly worthy of
      further enquiry.

PMID- 21190429
TI  - Direct visualization of phase separation induced by phenothiazine-type
      antipsychotic drugs in model lipid membranes.
AB  - Lipid rafts constitute dynamic assemblies within a bilayer, engaged in, e.g.,
      signal transduction, membrane trafficking and cell polarization. Despite wide
      interest in the process of domain formation in binary or ternary lipid model
      systems, only a limited number of papers are devoted to the influence of
      different additives on this process. In particular, works devoted to the role of
      drugs in raft formation are missing. In the present study, the influence of
      trifluoperazine, thioridazine and chlorpromazine on domain organization in raft
      mimicking model membranes was investigated. Using giant unilamellar vesicles
      formed from an equimolar DOPC:sphingomyelin:cholesterol mixture, we found that
      phenothiazines elevated the number of domains, decreased their area and markedly
      increased the total length of the domain border. The impact of studied drugs on
      phase separation in the raft lipid mixture was also confirmed by Laurdan
      generalized polarization measurements. Alteration of domain organization induced
      by antipsychotic drugs was very likely to arise from selective accumulation of
      phenothiazines in interfacial regions between liquid ordered and liquid
      disordered domains. Interpretation of the results allowed us to demonstrate new
      aspects underlaying mechanisms of action of phenothiazine-type antipsychotic
      drugs. To the best of our knowledge, this is the first report demonstrating the
      influence of drugs on domain morphology directly visualized in giant unilamellar
      vesicles.

PMID- 21190430
TI  - The effect of single cerebroside compounds on activation of BKCa channels.
AB  - We have previously shown that a mixture of cerebrosides obtained from dried
      tubers of herb Typhonium giganteum Engl. plays a neuroprotective role in the
      ischemic brain through its effect on activation of BK(Ca) channels. It is very
      curious to know whether a single pure cerebroside compound could activate the
      BK(Ca) channel as well. This study explored the possible effects of pure
      cerebroside compounds, termitomycesphins A and B, on the BK(Ca) channel
      activation. Both termitomycesphins A and B activated the BK(Ca) channels at
      micromole concentration without significant difference. Termitomycesphin A
      increased the single channel open probability of the BK(Ca) channels in a dose
      dependent manner without modifying the single channel conductance.
      Termitomycesphin A activated BK(Ca) channel more efficiently when it was applied
      to the cytoplasmic face of the membrane, suggesting that binding site for
      termitomycesphin A is located at the cytoplasmic side. Termitomycesphin A shifted
      the voltage-dependent activation curve to less positive membrane potentials and
      the Ca(2+)-dependent activation curve of the channel upwards, suggesting that
      termitomycesphin A could activate the channels even without intracellular free
      Ca(2+). Furthermore, STREX-deleted BK(Ca) channels were completely insensitive to
      termitomycesphin A, indicating that STREX domain is required for the activation
      of the BK(Ca) channel. These data provide evidence that termitomycesphins are
      potent in stimulating the activity of the BK(Ca) channels. As BK(Ca) channels are
      associated with pathology of many diseases, termitomycesphins might be used as
      therapeutic agents for treating these diseases through its regulatory effect on
      the BK(Ca) channels.

PMID- 21190431
TI  - Factor analysis of cardiometabolic risk factors clustering in children and
      adolescents.
AB  - BACKGROUND: Research on the clustering and relative importance of the metabolic
      syndrome components in children and adolescents is scarce. This study was
      conducted to explore the factor structure of the central metabolic syndrome
      variables in Jordanian children and adolescents using exploratory factor
      analysis. METHODS: This study included 665 children and adolescents who were
      identified in a national population-based household survey in Jordan. Their
      anthropometric and laboratory measurements were obtained. Factor analysis was
      performed on standardized variables to produce the minimum number of factors that
      retains as much of the total variance in the original data as possible. RESULTS:
      Factor analysis showed that one common factor is not sufficient to underlie
      metabolic syndrome. Four factors were extracted in the exploratory factor
      analysis-adiposity factor, blood pressure factor, lipids factor, and blood
      glucose factor. The cumulative percent of variance accounted for by the four
      factors together was 78.7% in male children, 86.9% in female children, 82.5% in
      male adolescents, and 83.4% in female adolescents. The adiposity factor accounted
      for the largest proportion of the total variance in the four groups. CONCLUSIONS:
      The factor analysis of cardiovascular risk clustering in Jordanian children and
      adolescents suggests that multiple factors account for the clustering of the
      metabolic syndrome components. Obesity accounts for the maximum variance in
      clustering and appears to be a more powerful correlate of cardiovascular risk in
      children and adolescents.

PMID- 21190432
TI  - Prostate diverticulum.
AB  - Pure cysts of the male genital system are rare, with the exception of epididymal
      cysts. Midline cystic masses in or near the prostate represent either an
      infectious etiology or utricular/Mullerian duct cysts. Prostatic diverticuli are
      extremely rare entities. A 61-year-old man presented with symptoms consistent
      with an active pelvic infection and computed tomography evidence of what was
      thought to be an intraprostatic abscess. Further studies revealed a large
      prostatic diverticulum and a poorly compliant bladder. The patient eventually
      required urinary diversion for symptom relief and upper urinary tract
      conservation.

PMID- 21190433
TI  - Parvovirus B19 infection in Hashimoto's thyroiditis, papillary thyroid carcinoma,
      and anaplastic thyroid carcinoma.
AB  - BACKGROUND: The human pathogenic parvovirus B19 (B19) has recently been detected
      in papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT) tissues at
      a high frequency in two studies of a Chinese cohort. We wanted to extend these
      data to include another cohort and expand the thyroid tumor tissue types
      assessed. In particular, we were interested to find whether B19 also infects
      anaplastic thyroid carcinoma (ATC), one of the most aggressive human cancers.
      METHODS: Commercially available thyroid tumor tissue arrays were used to detect
      B19 capsid protein by immunohistochemistry in various types of thyroid tumors and
      disorders. The arrays were representative of the four main types of thyroid
      tumors, as well as other thyroid autoimmune disorders such as HT and Graves'
      disease, and adenomas, goiters, lymphomas, and normal thyroid tissue. In total,
      at least 12 different types of thyroid conditions as well as normal tissue were
      represented, many with multiple subjects. RESULTS: Twenty-one of the 24 (88%) PTC
      tumors, 3 of the 3 ATC/undifferentiated tumors, and 3 of the 3 HT tissue samples
      were positive for B19 capsid protein by immunohistochemistry. The localization of
      the protein differed based on pathological disease type, with a nuclear to
      cytoplasmic shift seen from unaffected to tumor tissue. CONCLUSIONS: We extend
      the data available on B19 detection in the thyroid to show a high correlation of
      virus in another cohort of PTC and HT at the protein level. We also show, for the
      first time, B19 infection of much more highly aggressive ATC/undifferentiated
      tumors. Nuclear to cytoplasmic shift in B19 protein in cancer tissue suggests a
      possible link between B19 and thyroid cancer pathogenesis/progression.

PMID- 21190434
TI  - The ultrasonography features of hyalinizing trabecular tumor of the thyroid are
      more consistent with its benign behavior than cytology or frozen section
      readings.
AB  - BACKGROUND: Hyalinizing trabecular tumors of the thyroid (HTT) is a rare entity.
      Most behave as benign neoplasms, but their cytological features are challenging
      and can be similar to those of papillary thyroid carcinoma (PTC). The aim of this
      study was to compare the ultrasonography (US) readings of HTT with the cytology
      and frozen section readings. METHODS: We retrospectively analyzed the US and
      cytology features in 10 patients (mean age, 47.5 years, range 26-81; M:F, 1:9)
      seen between March 2006 and November 2009 who had a histopathological diagnosis
      of HTT. The US findings were categorized according to the size, shape, margin,
      echogenicity, echotexture, presence of hypoechoic halo, and microcalcifications.
      Preoperative fine-needle aspiration cytology, frozen section results, and
      surgical treatment were reviewed. US features of HTT were compared with those of
      other tumors including follicular adenomas, follicular variant of PTCs, and
      conventional PTC. RESULTS: Out of the 10 patients in our series, 7 underwent
      total thyroidectomy, and 3 had lobectomy. The sizes of the HTTs ranged from 0.6
      to 4.2 cm (mean, 1.77 cm). The most common US features were solid texture
      (10/10), oval to round shape (10/10), a well-defined aspect (10/10), hypoechoic
      character (8/10), heterogeneous character (7/10), the presence of a hypoechoic
      halo (8/10), and no microcalcifications (10/10). The US diagnosis was
      indeterminate in all but one case and that was read as a benign lesion. As far as
      the shape and margin US features were concerned, HTT was considered to be most
      similar to follicular adenomas and follicular variant of PTC, but not to
      classical PTC. The cytology reading was PTC in 6 of 10 cases, suspicious for PTC
      in 2, and a HTT versus PTC in 2. The histological diagnosis of frozen sections,
      when performed, was PTC in three, HTT in three, medullary thyroid carcinoma in
      two, and deferred in one. CONCLUSION: HTT often appears similar to follicular
      neoplasm on US, but it can be misjudged on cytology as PTC, even in frozen
      sections. HTT should be included in the list of discordant US-cytology readings
      of thyroid tumors. This rare tumor might be suspected more often preoperatively
      by careful attention to cytology in the context of the US reading.

PMID- 21190435
TI  - Expression and functional roles of Bradyrhizobium japonicum genes involved in the
      utilization of inorganic and organic sulfur compounds in free-living and
      symbiotic conditions.
AB  - Strains of Bradyrhizobium spp. form nitrogen-fixing symbioses with many legumes,
      including soybean. Although inorganic sulfur is preferred by bacteria in
      laboratory conditions, sulfur in agricultural soil is mainly present as
      sulfonates and sulfur esters. Here, we show that Bradyrhizobium japonicum and B.
      elkanii strains were able to utilize sulfate, cysteine, sulfonates, and sulfur
      ester compounds as sole sulfur sources for growth. Expression and functional
      analysis revealed that two sets of gene clusters (bll6449 to bll6455 or bll7007
      to bll7011) are important for utilization of sulfonates sulfur source. The
      bll6451 or bll7010 genes are also expressed in the symbiotic nodules. However, B.
      japonicum mutants defective in either of the sulfonate utilization operons were
      not affected for symbiosis with soybean, indicating the functional redundancy or
      availability of other sulfur sources in planta. In accordance, B. japonicum
      bacteroids possessed significant sulfatase activity. These results indicate that
      strains of Bradyrhizobium spp. likely use organosulfur compounds for growth and
      survival in soils, as well as for legume nodulation and nitrogen fixation.

PMID- 21190436
TI  - 'Ca. Liberibacter asiaticus' carries an excision plasmid prophage and a
      chromosomally integrated prophage that becomes lytic in plant infections.
AB  - Huanglongbing (HLB), also known as citrus greening, is a lethal disease of citrus
      caused by several species of 'Candidatus Liberibacter', a psyllid-transmitted,
      phloem-limited, alpha proteobacteria. 'Ca. Liberibacter asiaticus' is widespread
      in Florida citrus. The recently published 'Ca. L. asiaticus' psy62 genome,
      derived from a psyllid, revealed a prophage-like region of DNA in the genome, but
      phage have not been associated with 'Ca. L. asiaticus' to date. In the present
      study, shotgun sequencing and a fosmid DNA library of curated 'Ca. L. asiaticus'
      UF506, originally derived from citrus symptomatic for HLB, revealed two largely
      homologous, circular phage genomes, SC1 and SC2. SC2 encoded putative adhesin and
      peroxidase genes that had not previously been identified in 'Ca. L. asiaticus'
      and which may be involved in lysogenic conversion. SC2 also appeared to lack
      lytic cycle genes and replicated as a prophage excision plasmid, in addition to
      being found integrated in tandem with SC1 in the UF506 chromosome. By contrast,
      SC1 carried suspected lytic cycle genes and was found in nonintegrated, lytic
      cycle forms only in planta. Phage particles associated with 'Ca. L. asiaticus'
      were found in the phloem of infected periwinkles by transmission electron
      microscopy. In psyllids, both SC1 and SC2 were found only as prophage.

PMID- 21190437
TI  - Development of a host-induced RNAi system in the wheat stripe rust fungus
      Puccinia striiformis f. sp. tritici.
AB  - Rust fungi cause devastating diseases of wheat and other cereal species globally.
      Genetic resistance is the preferred method to control rusts but the effectiveness
      of race-specific resistance is typically transient due to the genetic plasticity
      of rust populations. The advent of RNA interference (RNAi) technology has shown
      promise for the engineering of resistance to some biotrophic pathogens in plants
      by altering the expression of essential pathogens' genes. Gene fragments from the
      rust fungi Puccinia striiformis f. sp. tritici or P. graminis f. sp. tritici were
      delivered to plant cells through the Barley stripe mosaic virus system, and some
      reduced the expression of the corresponding genes in the rust fungus. The ability
      to detect suppression was associated with the expression patterns of the fungal
      genes because reduction was only detected in transcripts with relatively high
      levels of expression in fungal haustoria. The results indicate that an in planta
      RNAi approach can be used in functional genomics research for rust fungi and that
      it could potentially be used to engineer durable resistance.

PMID- 21190438
TI  - A necrosis-inducing elicitor domain encoded by both symptomatic and asymptomatic
      Plantago asiatica mosaic virus isolates, whose expression is modulated by virus
      replication.
AB  - Systemic necrosis is the most destructive symptom induced by plant pathogens. We
      previously identified amino acid 1154, in the polymerase domain (POL) of RNA
      dependent RNA polymerase (RdRp) of Plantago asiatica mosaic virus (PlAMV), which
      affects PlAMV-induced systemic necrosis in Nicotiana benthamiana. By point
      mutation analysis, we show that amino acid 1,154 alone is not sufficient for
      induction of necrotic symptoms. However, PlAMV replicons that can express only
      RdRp, derived from a necrosis-inducing PlAMV isolate, retain their ability to
      induce necrosis, and transient expression of PlAMV-encoded proteins indicated
      that the necrosis-eliciting activity resides in RdRp. Moreover, inducible
      overexpression analysis demonstrated that the necrosis was induced in an RdRp
      dose-dependent manner. In addition, during PlAMV infection, necrotic symptoms are
      associated with high levels of RdRp accumulation. Surprisingly, necrosis
      eliciting activity resides in the helicase domain (HEL), not in the amino acid
      1,154-containing POL, of RdRp, and this activity was observed even in HELs of
      PlAMV isolates of which infection does not cause necrosis. Moreover, HEL-induced
      necrosis had characteristics similar to those induced by PlAMV infection.
      Overall, our data suggest that necrotic symptoms induced by PlAMV infection
      depend on the accumulation of a non-isolate specific elicitor HEL (even from
      nonnecrosis isolates), whose expression is indirectly regulated by amino acid
      1,154 that controls replication.

PMID- 21190439
TI  - Quantitative proteomic analysis of the interaction between the endophytic plant
      growth-promoting bacterium Gluconacetobacter diazotrophicus and sugarcane.
AB  - Gluconacetobacter diazotrophicus is a plant-growth-promoting bacterium that
      colonizes sugarcane. In order to investigate molecular aspects of the G.
      diazotrophicus-sugarcane interaction, we performed a quantitative mass
      spectrometry-based proteomic analysis by (15)N metabolic labeling of bacteria,
      root samples, and co-cultures. Overall, more than 400 proteins were analyzed and
      78 were differentially expressed between the plant-bacterium interaction model
      and control cultures. A comparative analysis of the G. diazotrophicus in
      interaction with two distinct genotypes of sugarcane, SP70-1143 and Chunee,
      revealed proteins with fundamental roles in cellular recognition. G.
      diazotrophicus presented proteins involved in adaptation to atypical conditions
      and signaling systems during the interaction with both genotypes. However, SP70
      1143 and Chunee, sugarcane genotypes with high and low contribution of biological
      nitrogen fixation, showed divergent responses in contact with G. diazotrophicus.
      The SP70-1143 genotype overexpressed proteins from signaling cascades and one
      from a lipid metabolism pathway, whereas Chunee differentially synthesized
      proteins involved in chromatin remodeling and protein degradation pathways. In
      addition, we have identified 30 bacterial proteins in the roots of the plant
      samples; from those, nine were specifically induced by plant signals. This is the
      first quantitative proteomic analysis of a bacterium-plant interaction, which
      generated insights into early signaling of the G. diazotrophicus-sugarcane
      interaction.

PMID- 21190440
TI  - Identification of new candidate pathogenicity factors in the xylem-invading
      pathogen Xanthomonas albilineans by transposon mutagenesis.
AB  - Xanthomonas albilineans is a xylem-invading pathogen that produces the toxin
      albicidin that blocks chloroplast differentiation, resulting in disease symptoms
      of sugarcane leaf scald. In contrast to other xanthomonads, X. albilineans does
      not possess a hypersensitive response and pathogenicity type III secretion system
      and does not produce xanthan gum. Albicidin is the only previously known
      pathogenicity factor in X. albilineans, yet albicidin-deficient mutant strains
      are still able to efficiently colonize sugarcane. To identify additional host
      adaptation or pathogenicity factors, sugarcane 'CP80-1743' was inoculated with
      1,216 independently derived Tn5 insertions in X. albilineans XaFL07-1 from
      Florida. Sixty-one Tn5 mutants were affected in development of leaf symptoms or
      in stalk colonization. The Tn5 insertion sites of these mutants were determined
      and the interrupted genes were identified using the recently available genomic
      DNA sequence of X. albilineans GPE PC73 from Guadeloupe. Several pathogenicity
      related loci that were not previously reported in Xanthomonas spp. were
      identified, including loci encoding hypothetical proteins, a membrane fusion
      protein conferring resistance to novobiocin, transport proteins, TonB-dependent
      outer-membrane transporters, and an OmpA family outer-membrane protein.

PMID- 21190441
TI  - Ralstonia solanacearum virulence increased following large interstrain gene
      transfers by natural transformation.
AB  - Horizontal gene transfer (HGT) is a major driving force of evolution and is also
      likely to play an important role in the threatening emergence of novel pathogens,
      especially if it involves distantly related strains with substantially different
      pathogenicity. In this study, the impact of natural transformation on
      pathogenicity in six strains belonging to the four phylotypes of the plant
      pathogenic bacterium Ralstonia solanacearum was investigated. The study focused
      on genomic regions that vary between donor and recipient strains and that carry
      genes involved in pathogenicity such as type III effectors. First, strains from
      R. solanacearum species complex were naturally transformed with heterologous
      genomic DNA. Transferred DNA regions were then determined by comparative genomic
      hybridization and polymerase chain reaction sequencing. We identified three
      transformant strains that acquired large DNA regions of up to 80 kb. In one case,
      strain Psi07 (phylotype IV tomato isolate) acquired 39.4 kb from GMI1000
      (phylotype I tomato isolate). Investigations revealed that i) 24.4 kb of the
      acquired region contained 20 new genes, ii) an allelic exchange of 12 genes
      occurred, and iii) 27 genes (33.4 kb) formerly present in Psi07 were lost.
      Virulence tests with the three transformants revealed a significant increase in
      the aggressiveness of BCG20 over its Psi07 parent on tomato. These findings
      demonstrate the potential importance of HGT in the pathogenic evolution of R.
      solanacearum strains and open new avenues for studying pathogen emergence.

PMID- 21190442
TI  - A large multicenter correlation study of thyroid nodule cytopathology and
      histopathology.
AB  - BACKGROUND: Fine-needle aspiration (FNA) biopsies are the cornerstone of
      preoperative evaluation of thyroid nodules, but FNA diagnostic performance has
      varied across different studies. In the course of collecting thyroid FNA
      specimens for the development of a molecular diagnostic test, local cytology and
      both local and expert panel surgical pathology results were reviewed. METHODS:
      Prospective FNAs were collected at 21 clinical sites. Banked FNAs were collected
      from two academic centers. Cytology and corresponding local and expert panel
      surgical pathology results were compared to each other and to a meta-review of 11
      recently published U.S.-based thyroid FNA studies. RESULTS: FNA diagnostic
      performance was comparable between the study specimens and the meta-review.
      Histopathology malignancy rates for prospective clinic FNAs were 34% for cytology
      indeterminate cases and 98% for cytology malignant cases, comparable to the
      figures found in the meta-review (34% and 97%, respectively). However,
      histopathology malignancy rates were higher for cytology benign cases in the
      prospective clinic FNA subcohort (11%) than in the meta-review (6%, with meta
      review rates of 10% at community sites and 2% at academic centers, p < 0.0001).
      Resection rates for prospective clinic FNAs were also comparable to the meta
      review for both cytology indeterminate cases (62% vs. 59%, respectively) and
      cytology malignant cases (82% vs. 81%, respectively). Surgical pathology
      categorical disagreement (benign vs. malignant diagnosis) was higher between
      local pathology and a consensus of the two expert panelists (11%) than between
      the two expert panelists both pre- (8%) and postconferral (3%). CONCLUSIONS:
      Although recent guidelines for FNA biopsy and interpretation have been published,
      the rates of false-positive and false-negative results remain a challenge. Two
      thirds of cytology indeterminate cases were benign postoperatively and may
      decrease with the development of an accurate molecular diagnostic test. High
      disagreement rates between local and expert panel histopathology diagnosis
      suggests that central review for surgical diagnoses should be used when
      developing diagnostic tests based on resected thyroid specimens.

PMID- 21190443
TI  - Shared sporadic and somatic thyrotropin receptor mutations display more active in
      vitro activities than familial thyrotropin receptor mutations.
AB  - BACKGROUND: Germline thyrotropin receptor (TSHR) mutations are associated with
      sporadic congenital nonautoimmune hyperthyroidism and familial nonautoimmune
      hyperthyroidism. Somatic TSHR mutations are associated with toxic thyroid nodules
      (TTNs). The objective of the study was to define a relation of the clinical
      appearance and the in vitro activity (IVA) of the TSHR mutations described by
      several authors for these thyroid disorders. METHODS: We analyzed the IVAs
      published as linear regression analysis (LRA) of the constitutive activity as a
      function of the TSHR expression and the basal cyclic adenosine monophosphate
      (cAMP) values to determine differences between exclusively somatic, exclusively
      familial, and shared sporadic and somatic TSHR-mutations. Further, we
      investigated correlations of the LRAs/basal cAMP values with clinical activity
      characteristics (CACs) of TTNs, such as largest diameter of the TTN and the age
      of the patient at thyroid surgery. RESULTS: Shared sporadic and somatic mutations
      showed higher median LRA (14.5) and higher median basal cAMP values (fivefold)
      than exclusively familial mutations (6.1, p = 0.0002; 2.9-fold, p < 0.0001,
      respectively). Moreover, mutations shared between sporadic congenital
      nonautoimmune hyperthyroidism and toxic thyroid nodules (TTNs) showed higher
      median LRA/basal cAMP values (p < 0.0001) than exclusively somatic mutations in
      TTNs (5.1; 3.89-fold, respectively). Exclusively somatic mutations and
      exclusively familial mutations showed no significant difference in their median
      LRA values (p = 0.786) but a significant difference for basal cAMP values (p =
      0.0006). The two examined CACs showed no correlation with the IVA characterized
      by LRA/basal cAMP values or with the presence or absence of a TSHR-mutation.
      CONCLUSIONS: This systematic analysis of published constitutively activating TSHR
      mutations, their CACs, and their IVA provides evidence for higher IVA of shared
      sporadic and somatic TSHR mutations as compared with familial TSHR mutations.
      CACs of somatic TSHR mutations in TTNs did not have a clear association with the
      IVA as characterized by LRA or basal cAMP values.

PMID- 21190444
TI  - Prevalence, clinicopathologic features, and somatic genetic mutation profile in
      familial versus sporadic nonmedullary thyroid cancer.
AB  - BACKGROUND: Although hereditary nonmedullary thyroid cancer is recognized as a
      distinct and isolated familial syndrome, the precise prevalence and genetic basis
      are poorly understood. Moreover, whether familial nonmedullary thyroid cancer
      (FNMTC) has a more aggressive clinical behavior is controversial. The objectives
      of this study were to determine the prevalence of FNMTC, and compare the extent
      of disease and tumor somatic genetic alteration in patients with familial and
      sporadic papillary thyroid cancer. METHODS: The main study entry criterion was
      patients who had a thyroid nodule that required a clinical evaluation with fine
      needle aspiration biopsy and or thyroidectomy. A family history questionnaire was
      used to determine the presence of familial and sporadic thyroid cancer. Thyroid
      nodule fine-needle aspiration biopsy samples and tumor tissue at the time of
      thyroidectomy were used to test for somatic genetic mutations (BRAF V600E, NRAS,
      KRAS, NTRK1, RET/PTC1, and RET/PTC3). RESULTS: There were 402 patients with 509
      thyroid nodules enrolled in the study. The prevalence of FNMTC was 8.8% in all
      patients with thyroid cancer and 9.4% in patients with only papillary thyroid
      cancer. None of the patients with FNMTC had another familial cancer syndrome.
      There was no significant difference in gender, tumor size, lymph node metastasis,
      and overall stage between sporadic and familial cases of thyroid cancer. Patients
      with FNMTC were younger at diagnosis than patients with sporadic papillary
      thyroid cancer (p < 0.002). Seventy-nine of the 504 thyroid nodules had somatic
      genetic mutations (29 BRAF V600E, 29 NRAS, 8 KRAS, 1 NTRK1, 4 RET/PTC1, and 8
      RET/PTC3). There was no significant difference in the number or type of somatic
      mutations between sporadic and hereditary cases of papillary thyroid cancer.
      CONCLUSIONS: We found a higher prevalence of FNMTC in patients with papillary
      thyroid cancer than previously reported. Patients with FNMTC present at a younger
      age. Somatic mutations and extent of disease are similar in sporadic and FNMTC
      cases.

PMID- 21190445
TI  - Thyroid hormones influence human dendritic cells' phenotype, function, and
      subsets distribution.
AB  - BACKGROUND: Dendritic cells (DCs) are the most effective antigen-presenting cells
      and key regulators of immune response. The immunoregulatory properties of DCs
      strongly depend on the microenvironment in which DCs have been matured and
      activated. Thyroid hormones are an important part of this environment and
      regulate many vital processes including growth and cellular metabolism. The aim
      of the study was an analysis of the influence of thyroid hormones on blood DC
      subtypes ex vivo, including the surface expression of molecules involved in
      antigen presentation, costimulation, and maturation, as well as on functional
      properties of DCs in vitro. METHODS: Blood samples for the quantitative and
      phenotypic analysis of peripheral blood plasmacytoid and myeloid DC subtypes were
      collected from thyroidectomized patients at two time points: (i) at the time of
      the so-called stimulation with endogenous thyrotropin-a group of hypothyroid
      patients after l-thyroxine (L-T(4)) withdrawal (pretreatment group)-and (ii)
      after 2 months of L-T(4) administration for thyrotropin suppression-a
      posttreatment group. The phenotype of DCs including HLA-DR, costimulatory
      molecules (CD40, CD80, and CD86), and maturation marker CD83 was assessed by flow
      cytometry. The influence of isolated peripheral blood DCs on autologous
      peripheral blood mononuclear cell proliferation and cytokine secretion
      (interferon alpha, interleukin-12) under triiodothyronine (T(3)) deficiency or
      T(3) excess was investigated in culture experiments. RESULTS: The percentage of
      peripheral blood plasmacytoid and myeloid DCs was higher after L-T(4)
      administration when compared with the pretreatment group. Moreover, the
      expression of CD86 on both DC subtypes was higher in the L-T(4) treated than in
      the hypothyroid patients. In the in vitro experiments, T(3) stimulation increased
      CD86 expression on cultured DCs. The phenotypic difference was paralleled by
      enhanced ability of T(3)-stimulated DCs to activate interleukin-12 secretion and
      proliferation of autologous peripheral blood mononuclear cells (PBMLs) in
      coculture experiments. CONCLUSIONS: In the present study, we provide for the
      first time an evidence that the thyrometabolic status has an influence on the
      phenotype and function of human peripheral blood DCs. This observation may be of
      potential importance for the understanding of the pathogenesis of immune and
      endocrine disorders.

PMID- 21190446
TI  - Outcome of very long-term treatment with antithyroid drugs in Graves'
      hyperthyroidism associated with Graves' orbitopathy.
AB  - BACKGROUND: It is still debated which treatment modality for Graves'
      hyperthyroidism (GH) is most appropriate when Graves' orbitopathy (GO) is
      present. The preference in our center has been always to continue antithyroid
      drugs for GH (as the block-and-replace [B-R] regimen) until all medical and/or
      surgical treatments for GO are concluded and the eye disease does not require any
      further therapy (except prescription of lubricants). This usually takes more than
      2 years. The aim of this study was to evaluate the outcome of long-term B-R
      regimen for GH in GO patients by assessment (after discontinuation of B-R) of (a)
      the recurrence rate of GH and (b) the relapse rate of GO and its association with
      recurrent GH and/or (131)I therapy. METHODS: A retrospective follow-up study was
      done among all patients referred to the Academic Medical Center in Amsterdam
      between 1995 and 2005 for GO. The inclusion criteria for the study were a history
      of GH and GO and a history of treatment for GH with a B-R regimen for more than 2
      years. The exclusion criteria were a history of (131)I therapy or thyroidectomy
      before the end of GO treatment. A questionnaire was sent to 255 patients and
      returned by 114. Of these patients, 73 qualified for the study. Recurrences of GH
      and/or GO as indicated by returned questionnaires were checked with treating
      physicians. RESULTS: Patients were treated with B-R for a median of 41 months
      (range: 24-132). The median follow-up after discontinuation of the B-R regimen
      was 57 months (range: 12-170). Recurrent GH occurred in 27 of the 73 study
      patients (37%) at a median of 3 months (range: 1-65) after withdrawal of
      antithyroid drug therapy. Nineteen of the 27 patients with recurrent
      hyperthyroidism were treated with (131)I therapy. A relapse of GO was not
      encountered in any of the 73 patients. CONCLUSION: The study suggests that long
      term B-R treatment of GH in GO patients is associated with a recurrence rate of
      hyperthyroidism of about 37%. With the regimen employed, recurrence of
      hyperthyroidism and recurrence of hyperthyroidism followed by treatment with
      (131)I appears not to be a likely cause of relapse of GO. The data suggest that B
      R treatment of GH until GO has become inactive and does not require any further
      treatment is a feasible option and does not jeopardize the improvement that
      occurred in GO.

PMID- 21190447
TI  - Normal parathyroid hormone levels do not exclude permanent hypoparathyroidism
      after thyroidectomy.
AB  - BACKGROUND: Permanent hypoparathyroidism has become the most common and the most
      severe complication after thyroid surgery. In our experience, some patients
      suffer from permanent hypocalcemia and related symptoms despite normal
      parathyroid hormone (PTH) values after thyroid surgery. The aim of this work was
      to present a series of such patients with long-term hypocalcemia and normal PTH
      values to evaluate to what extent parathyroid function was impaired by
      thyroidectomy, and determine whether irregularities of bone and calcium
      metabolism were associated with this phenomenon. METHODS: We present a series of
      eight patients with normal PTH and subnormal calcium levels at follow-up 2 months
      after thyroid surgery. Outcome parameters were intra- and postoperative PTH and
      calcium kinetics, and the following markers of calcium and bone metabolism at
      long-term follow-up: serum calcium, total serum albumin, ionized calcium,
      magnesium, PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, urinary calcium,
      urinary creatinine, osteocalcin, c-terminal telopeptide of type I collagen, and
      alkaline phosphatase. RESULTS: All patients had normal calcium and PTH levels at
      the start of the operation. The intraoperative decline in PTH was >90%; the
      trough (3.3% of preoperative value) was reached 3 hours after surgery. Patients
      underwent complete determination of bone metabolism parameters during long-term
      follow-up 13.8 +/- 2.4 months after surgery. Hypocalcemia was found in all eight
      patients, as well as PTH levels within the normal range. In three patients (3/8 =
      37.5%), none of the other parameters was altered. In the remaining five patients,
      only isolated abnormalities in bone and calcium metabolism parameters were found
      (i.e., alterations in urinary calcium, thyrotropin, 25-hydroxyvitamin D,
      osteocalcin, and c-terminal telopeptide of type I collagen). CONCLUSIONS: An
      intraoperative injury to the parathyroid glands or their vascularization is the
      likely contributing factor to the development of permanent hypocalcemia with
      normal PTH values after thyroid surgery. The remaining parathyroid tissue is
      subject to a maximum stimulus by hypocalcemia and, therefore, is able to maintain
      PTH values in the normal range. These are still too low to re-establish normal
      serum calcium levels. In these patients, the term "hypoparathyroidism" might be
      replaced with "parathyroid insufficiency."

PMID- 21190449
TI  - Rethinking safety-net access for the uninsured.

PMID- 21190448
TI  - Thyroid pathology in PTEN-hamartoma tumor syndrome: characteristic findings of a
      distinct entity.
AB  - BACKGROUND: Phosphatase and tensin homolog deleted on chromosome ten (PTEN)
      hamartoma tumor syndrome (PHTS) is a complex disorder caused by germline
      inactivating mutations of the PTEN tumor suppressor gene. PHTS includes Cowden
      syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), and Proteus-like
      syndromes. Affected individuals develop both benign and malignant tumors in a
      variety of tissues, including the thyroid. This study is to better characterize
      and describe the thyroid pathology within the different entities of this
      syndrome, and examine whether there is an association between specific thyroid
      findings and different PTEN mutations. METHODS: Twenty patients with known PTEN
      mutations, and/or clinical diagnosis of PHTS, and thyroid pathology were
      identified: 14 with CS and 6 with BRRS. RESULTS: Thyroid pathology findings were
      as follows: multiple adenomatous nodules in a background of lymphocytic
      thyroiditis (LT) in 75%, papillary carcinoma in 60%, LT alone in 55%, follicular
      carcinoma in 45%, C-cell hyperplasia in 55%, and follicular adenomas in 25%.
      Within the papillary carcinoma group, there were 6 microcarcinomas, 5 follicular
      variants, and 1 classical type. CONCLUSIONS: There were no morphologic
      differences between the thyroid findings in CS and BRRS. Also, there was no
      correlation between specific PTEN germline mutations (exons 5, 6, and 8) and
      pathologic findings. Distinctive and characteristic findings in PHTS include
      multiple unique adenomatous nodules in a background of LT, and C-cell
      hyperplasia; it is vital that pathologists recognize the classical histologic
      features of this syndrome to alert clinicians to the possibility of this syndrome
      in their patients.

PMID- 21190451
TI  - Images in clinical medicine. Opsoclonus due to diphenhydramine poisoning.

PMID- 21190450
TI  - Improved mobilization of the CD34(+) and CD133(+) bone marrow-derived circulating
      progenitor cells by freshly isolated intracoronary bone marrow cell
      transplantation in patients with ischemic heart disease.
AB  - Cell therapy is a promising novel option for treatment of cardiovascular disease.
      Because the role of bone marrow-derived circulating progenitor cells (BM-CPCs)
      after cell therapy is less clear, we analyzed in this randomized, controlled
      study the influence of intracoronary autologous freshly isolated bone marrow cell
      transplantation (BMC-Tx) by using a point-of-care system on cardiac function and
      on the mobilization of BM-CPCs in patients with ischemic heart disease (IHD).
      Fifty-six patients with IHD were randomized to either receive freshly isolated
      BMC-Tx or a control group that did not receive cell therapy. Peripheral blood
      concentrations of CD34/45(+) and CD133/45(+) CPCs were measured by flow cytometry
      pre-, immediately post-, and at 3, 6, and 12 months postprocedure in both groups.
      Global ejection fraction and the size of infarct area were determined by left
      ventriculography. We observed in patients with IHD after intracoronary
      transplantation of autologous freshly isolated BMCs-Tx at 3 and 12 months follow
      up a significant reduction of the size of infarct area and increase of global
      ejection fraction as well as infarct wall movement velocity. The mobilization of
      CD34/45(+) and CD133/45(+) BM-CPCs significantly increased at 3, 6, and 12 months
      after cell therapy when compared with baseline in patients with IHD, although no
      significant changes were observed between pre- and immediately postintracoronary
      cell therapy administration. In the control group without cell therapy, there was
      no significant difference of CD34/45(+) and CD133/45(+) BM-CPCs mobilization
      between pre- and at 3, 6, and 12 months postcoronary angiography. Intracoronary
      transplantation of autologous freshly isolated BMCs by using a point-of-care
      system in patients with IHD may enhance and prolong the mobilization of
      CD34/45(+) and CD133/45(+) BM-CPCs in peripheral blood and this might increase
      the regenerative potency in IHD.

PMID- 21190452
TI  - Sleep deprivation, elective surgical procedures, and informed consent.

PMID- 21190454
TI  - Residual NADPH oxidase and survival in chronic granulomatous disease.
AB  - BACKGROUND: Failure to generate phagocyte-derived superoxide and related reactive
      oxygen intermediates (ROIs) is the major defect in chronic granulomatous disease,
      causing recurrent infections and granulomatous complications. Chronic
      granulomatous disease is caused by missense, nonsense, frameshift, splice, or
      deletion mutations in the genes for p22(phox), p40(phox), p47(phox), p67(phox)
      (autosomal chronic granulomatous disease), or gp91(phox) (X-linked chronic
      granulomatous disease), which result in variable production of neutrophil-derived
      ROIs. We hypothesized that residual ROI production might be linked to survival in
      patients with chronic granulomatous disease. METHODS: We assessed the risks of
      illness and death among 287 patients with chronic granulomatous disease from 244
      kindreds. Residual ROI production was measured with the use of superoxide
      dependent ferricytochrome c reduction and flow cytometry with dihydrorhodamine
      oxidation assays. Expression of NADPH oxidase component protein was detected by
      means of immunoblotting, and the affected genes were sequenced to identify causal
      mutations. RESULTS: Survival of patients with chronic granulomatous disease was
      strongly associated with residual ROI production as a continuous variable,
      independently of the specific gene affected. Patients with mutations in p47(phox)
      and most missense mutations in gp91(phox) (with the exception of missense
      mutations in the nucleotide-binding and heme-binding domains) had more residual
      ROI production than patients with nonsense, frameshift, splice, or deletion
      mutations in gp91(phox). After adolescence, mortality curves diverged according
      to the extent of residual ROI production. CONCLUSIONS: Patients with chronic
      granulomatous disease and modest residual production of ROI have significantly
      less severe illness and a greater likelihood of long-term survival than patients
      with little residual ROI production. The production of residual ROI is predicted
      by the specific NADPH oxidase mutation, regardless of the specific gene affected,
      and it is a predictor of survival in patients with chronic granulomatous disease.
      (Funded by the National Institutes of Health.).

PMID- 21190455
TI  - Collaborative care for patients with depression and chronic illnesses.
AB  - BACKGROUND: Patients with depression and poorly controlled diabetes, coronary
      heart disease, or both have an increased risk of adverse outcomes and high health
      care costs. We conducted a study to determine whether coordinated care management
      of multiple conditions improves disease control in these patients. METHODS: We
      conducted a single-blind, randomized, controlled trial in 14 primary care clinics
      in an integrated health care system in Washington State, involving 214
      participants with poorly controlled diabetes, coronary heart disease, or both and
      coexisting depression. Patients were randomly assigned to the usual-care group or
      to the intervention group, in which a medically supervised nurse, working with
      each patient's primary care physician, provided guideline-based, collaborative
      care management, with the goal of controlling risk factors associated with
      multiple diseases. The primary outcome was based on simultaneous modeling of
      glycated hemoglobin, low-density lipoprotein (LDL) cholesterol, and systolic
      blood-pressure levels and Symptom Checklist-20 (SCL-20) depression outcomes at 12
      months; this modeling allowed estimation of a single overall treatment effect.
      RESULTS: As compared with controls, patients in the intervention group had
      greater overall 12-month improvement across glycated hemoglobin levels
      (difference, 0.58%), LDL cholesterol levels (difference, 6.9 mg per deciliter
      [0.2 mmol per liter]), systolic blood pressure (difference, 5.1 mm Hg), and SCL
      20 depression scores (difference, 0.40 points) (P<0.001). Patients in the
      intervention group also were more likely to have one or more adjustments of
      insulin (P=0.006), antihypertensive medications (P<0.001), and antidepressant
      medications (P<0.001), and they had better quality of life (P<0.001) and greater
      satisfaction with care for diabetes, coronary heart disease, or both (P<0.001)
      and with care for depression (P<0.001). CONCLUSIONS: As compared with usual care,
      an intervention involving nurses who provided guideline-based, patient-centered
      management of depression and chronic disease significantly improved control of
      medical disease and depression. (Funded by the National Institute of Mental
      Health; ClinicalTrials.gov number, NCT00468676.).

PMID- 21190456
TI  - Novel deer-associated parapoxvirus infection in deer hunters.
AB  - Parapoxviruses are a genus of the double-stranded DNA family of poxviruses that
      infect ruminants, and zoonotic transmission to humans often results from
      occupational exposures. Parapoxvirus infection in humans begins with an
      incubation period of 3 to 7 days, followed by the development of one or more
      erythematous maculopapular lesions that evolve over the course of several weeks
      into nodules. In 2009, parapoxvirus infection was diagnosed in two deer hunters
      in the eastern United States after the hunters had field-dressed white-tailed
      deer. We describe the clinical and pathological features of these infections and
      the phylogenetic relationship of a unique strain of parapoxvirus to other
      parapoxviruses. Deer populations continue to increase, leading to the possibility
      that there will be more deer-associated parapoxvirus infections.

PMID- 21190457
TI  - Homozygous BUB1B mutation and susceptibility to gastrointestinal neoplasia.
AB  - A patient received a diagnosis of adenocarcinoma of the ampulla of Vater at 34
      years of age. Two decades later, adenomatous polyps were found, followed by
      multiple primary invasive adenocarcinomas of both the colon and the stomach.
      Premature chromatid separation and mosaic variegated aneuploidy, combined with
      structural chromosomal abnormalities, were detected in his cells. We identified a
      germline homozygous intronic mutation, c.2386-11A->G, in the spindle-assembly
      checkpoint gene BUB1B, which creates a de novo splice site that is favored over
      the authentic (i.e., preferentially used) site. Our findings expand the phenotype
      associated with BUB1B mutations and the mosaic variegated aneuploidy syndrome to
      include common adult-onset cancers and provide evidence for the interdependency
      of the APC protein (encoded by the adenomatous polyposis coli gene) and the BUBR1
      protein (encoded by BUB1B) in humans. (Funded by the Turner Family Cancer
      Research Fund and others.).

PMID- 21190459
TI  - Images in clinical medicine. Ischemic gangrene.

PMID- 21190458
TI  - General anesthesia, sleep, and coma.

PMID- 21190460
TI  - Case records of the Massachusetts General Hospital. Case 40-2010. A 68-year-old
      woman with chest pain during an airplane flight.

PMID- 21190461
TI  - The spindle-assembly checkpoint, aneuploidy, and gastrointestinal cancer.

PMID- 21190462
TI  - Rosiglitazone, PPARgamma, and type 2 diabetes.

PMID- 21190463
TI  - Susceptibility to exacerbation in COPD.

PMID- 21190464
TI  - Susceptibility to exacerbation in COPD.

PMID- 21190465
TI  - Susceptibility to exacerbation in COPD.

PMID- 21190466
TI  - Susceptibility to exacerbation in COPD.

PMID- 21190468
TI  - Sleep deprivation and elective surgery.

PMID- 21190469
TI  - Idiopathic urgency urinary incontinence.

PMID- 21190474
TI  - Characterization of extended-spectrum beta-lactamases and qnr plasmid-mediated
      quinolone resistance in German isolates of Enterobacter species.
AB  - The objective of this study was to characterize the antimicrobial resistance
      patterns of 100 clinical isolates of Enterobacter spp. with special regard to the
      occurrence of extended-spectrum beta-lactamases (ESBLs) and plasmid-mediated
      quinolone resistance by qnr-determinants. The rate of ESBL- and qnr-positive
      isolates was 7% and 14%, respectively. Thirteen isolates harbored a qnrA1, and a
      further isolate harbored a qnrB4 gene. Moreover, qnr-determinants were
      significantly associated with ESBL-expression. No carbapeneme or tigecycline
      resistance was detected in the collective tested. To conclude, these data confirm
      the increase of multiple antimicrobial resistance mechanisms in Enterobacter spp.

PMID- 21190475
TI  - Persistence and spread of qnr, extended-spectrum beta-lactamase, and ampC
      resistance genes in the digestive tract of chickens.
AB  - The aim of this assay was to develop an experimental model of digestive
      colonization of chickens with bacteria harboring qnr, extended-spectrum beta
      lactamase, or ampC genes. Specific pathogen-free chickens were orally inoculated
      with two Escherichia coli strains containing either the plasmid pMG252 bearing
      bla(FOX) and qnrA genes, or pMG298 bearing bla(CTX-M) and qnrB genes. Analysis of
      strains isolated from fecal samples showed that the two strains were able to
      persist for several weeks in the digestive flora of inoculated birds and could
      rapidly spread to noninoculated ones. However, the multi-resistant isolates were
      maintained as a small proportion of the overall enterobacterial population. The
      qnr, extended-spectrum beta-lactamase, and ampC resistance genes could be
      transferred, in vivo, in the absence of selective pressure, to other chicken E.
      coli or Klebsiella pneumoniae isolates.

PMID- 21190476
TI  - Diversity of beta-lactamases in Pseudomonas aeruginosa isolates producing metallo
      beta-lactamase in two Tunisian hospitals.
AB  - This study was conducted to identify the beta-lactamase content of 30 metallo
      beta-lactamase-producing Pseudomonas aeruginosa isolated in 2007 from two
      Tunisian hospitals and to investigate their genetic relatedness. All these
      isolates produced VIM-2. bla(PER-1), bla(PSE-1), bla(OXA-2), and bla(OXA-10) were
      identified in 17, 5, 21, and 1 isolates, respectively. These enzymes were often
      associated in the same isolate: 26 isolates had at least two beta-lactamases. The
      predominant serotype was O12. Pulsed-field gel electrophoresis revealed genetic
      diversity among the metallo-beta-lactamase-producing P. aeruginosa isolates. This
      is the first report on the existence of bla(PER-1), bla(PSE-1), bla(OXA-2), and
      bla(OXA-10) in Tunisia.

PMID- 21190477
TI  - Laparoscopic Nissen fundoplication for the management of failed Angelchik
      prosthesis.
AB  - BACKGROUND: Angelchik is a silicone gel-filled prosthesis that was historically
      placed around the gastro-esophageal junction like a horse's halter for the
      treatment of gastro-esophageal reflux disease. It was first described by
      Angelchik and Cohen in 1979, after which its usage expanded due to its simplicity
      and ease of insertion by open surgery. However, the use of this device has
      largely been abandoned due to numerous complications and a consequent high
      removal rate. The most common complications cited have been dysphagia,
      disruption, migration, and erosion into the stomach. Although many reports of
      Angelchik prosthesis removal have appeared in the literature, we present a case
      of laparoscopic removal of this device that has been inserted 25 years ago,
      followed immediately by Nissen fundoplication. The main indication for operation
      was recurrent severe reflux symptoms refractory to medical treatment. METHODS:
      Case note review and literature search. RESULTS: There was no intraoperative or
      postoperative complication although the procedure was extremely challenging
      laparoscopically primarily due to attenuated anatomy and dense adhesions. The
      patient made an uneventful recovery with subsequent complete resolution of
      symptoms. CONCLUSION: Patients who have severe recurrent gastro-esophageal reflux
      disease symptoms refractory to medical treatment after placement of an Angelchik
      prosthesis can be treated by laparoscopic removal of the device followed by
      Nissen fundoplication.

PMID- 21190478
TI  - Laparoscopic ureterolithotomy as a primary modality for large proximal ureteral
      calculi: comparison to rigid ureteroscopic pneumatic lithotripsy.
AB  - OBJECTIVE: To define the role of laparoscopic ureterolithotomy (LU) as a primary
      modality for large proximal ureteral stones, we compared the outcomes of primary
      LU with those of ureterorenoscopy (URS), the currently established modality in
      this circumstance. MATERIALS AND METHODS: Among 71 patients who underwent LU in
      our institution between February 2005 and January 2010, 32 patients with stone
      size over 1.5 cm who underwent LU as a primary modality without prior shockwave
      lithotripsy or URS and for whom LU was conducted as a separate procedure were
      exclusively enrolled. Based on preoperative characteristics of patients and
      stones, this patient group was matched with the URS group (n = 32, rigid
      pneumatic lithotripter) during the same period. RESULTS: The LU group and the URS
      group were similar in age, gender distribution, body mass index, stone size (18.1
      +/- 4.2 versus 17.9 +/- 3.6 mm; P = .88), and stone location. Members of the LU
      group required a longer operative time (118 +/- 53 versus 59 +/- 41 minutes; P <
      .001) and hospital stay (5.9 +/- 2.1 versus 3.4 +/- 2.4 days; P < .001) and had
      greater blood loss (155 +/- 62 mL). However, stone clearance rate (no remnant
      stone in postoperative X-ray of the kidney, ureter, and bladder) in a single
      session was marginally higher in the LU group (93.8% versus 68.8%; P = .06).
      Total complication rate was not significant and was slightly higher in the URS
      group (12.5% versus 21.9%, P = .51). Stone migration into the kidney (n = 2
      versus 5), ureteral perforation (n = 0 versus 3), open conversion (n = 1 versus
      2), and ureteral stricture (n = 1 versus 2), as long-term complications, occurred
      more frequently in the URS group. CONCLUSIONS: For large proximal ureteral
      stones, LU can be conducted safely as a first-line procedure without increase of
      complication rate, compared with conventional URS. Although LU required a
      prolonged operative time and a longer hospital stay and blood loss was greater,
      our data showed an advantage of LU in high clearance rate in a single procedure.

PMID- 21190479
TI  - The technique of laparoscopic pelvic ultrasonography for metastatic lymph node.
AB  - Many reports have provided evidence to support the effective use of diagnostic
      laparoscopy and laparoscopic ultrasonography (LUS) to determine if patients with
      upper abdominal malignant diseases are operable so that unnecessary laparotomy
      can be avoided. LUS is less frequently applied to patients with pelvic
      malignancies and this is probably related to the technical difficulties. We have
      developed the LUS technique in examining the pelvic nodes for metastasis
      systematically and have applied it to 241 cervical cancer patients. The procedure
      is safe and not associated with any major morbidity. The mean duration of pelvic
      node assessment by LUS is 14 minutes and the procedure can be satisfactorily
      completed in 98% of patients. The accuracy, sensitivity, specificity, positive
      predictive value, and negative predictive value of LUS in detecting pelvic nodal
      metastasis were 81.2%, 55.6%, 88.4%, 57.7%, and 87.5%, respectively, in patients
      scheduled for radical hysterectomy. In this report, we describe the LUS technique
      in detail and demonstrate important landmarks that provide useful orientation
      during an LUS examination. The technical limitations and pitfalls are also
      discussed.

PMID- 21190480
TI  - Portal vein thrombosis after laparoscopic and open splenectomy.
AB  - INTRODUCTION: Portal vein thrombosis (PVT) could be a life-threatening
      complication after splenectomy if not diagnosed promptly and treated properly.
      Risk factors of PVT are not completely clarified. Spleen size and underlying
      hematologic diseases are main potential risk factors for this complication.
      Laparoscopic surgery might increase the risk of developing PVT, as it reduces the
      blood flow in the portal system due to the pneumoperitoneum but, on the other
      hand, it seems to be associated with less postoperative modifications of
      coagulation parameters than open surgery, thus preventing PVT itself. The authors
      reviewed their series on open and laparoscopic splenectomies, pointing out their
      experience on PVT and discussing their surveillance and prophylaxis programs to
      prevent this complication. MATERIALS AND METHODS: In this series, the authors
      report their experience on postsplenectomy PVT in 162 patients who have been
      splenectomised (102 operated on laparoscopically and 60 by open surgery).
      RESULTS: PVT was clinically observed in 1 case out of 60 open splenectomies and
      in 3 cases out of 102 laparoscopic procedures. Patients were treated with
      conservative anticoagulation therapy. In one case, additional ileal resection was
      needed. Mortality was 0%. CONCLUSION: Low-molecular-weight heparin should be
      administered to all patients who have been splenectomised, especially if they are
      at high risk of PVT. If symptoms appear, patients need to be treated with high
      dose heparin followed, after at least 3 weeks, by oral anticoagulant therapy.

PMID- 21190481
TI  - Early experience with single-incision thoracoscopic surgery in the pediatric
      population.
AB  - INTRODUCTION: Single-incision pediatric endosurgery is gaining popularity in
      children. We have recently applied the single-incision approach for thoracoscopic
      procedures. We report our initial experience with single-incision thoracoscopic
      surgery in the pediatric population. METHODS: A retrospective chart review of the
      first 10 single-incision thoracoscopic operations done at our institution was
      conducted. The patients' mean age and weight and the median operative time,
      postoperative length of stay, and time until discontinuation of chest tubes were
      determined. RESULTS: The 10 procedures were performed in eight patients (two
      patients each had bilateral procedures). The procedures performed included wedge
      resection and mechanical pleurodesis for spontaneous pneumothorax (n = 7), wedge
      biopsies for lymphoma (n = 1) and chronic granulomatous disease (n = 1), and
      resection of an apical extrapulmonary neuroblastoma (n = 1). All of the
      procedures were completed without intraoperative complication or significant
      blood loss. In each case, multiple trocars and/or unsheathed instruments were
      passed through a single small incision, which was subsequently used for the chest
      tube(s). The mean patient age was 13.5 years (range 3-18 years). The mean weight
      was 47 kilograms (range 16-63 kg). The median operative time was 64 minutes
      (range 50-201 minutes). The median postoperative length of stay was 7 days (range
      3-19 days). The median time until chest tube removal was 3 days (range 2-15
      days). The mean follow-up was 7 months (range 3-12 months). One patient developed
      a recurrent pneumothorax and persistent air leak after having undergone a wedge
      resection and pleurodesis for a spontaneous pneumothorax and required a
      reoperation. CONCLUSION: Single-incision thoracoscopic surgery is a feasible
      alternative to the traditional multiple-incision approach in the pediatric
      population. The in-line positioning of the camera and instruments often proves to
      be an advantage rather than a hindrance.

PMID- 21190482
TI  - Laparoscopic extravesical transperitoneal approach following the lich-gregoir
      procedure in refluxing duplicated collecting systems: initial experience.
AB  - INTRODUCTION: Vesicoureteral reflux (VUR) represents one of the most significant
      risk factors for acute pyelonephritis in children. Nephropathy with renal
      scarring is still the most concerning issue in VUR. Surgical correction to
      eliminate VUR is an important part of its management and this need is increasing
      for duplicated collecting systems (DCS). Laparoscopy may have a place in the
      treatment of VUR. We report our initial experience in the treatment of refluxing
      DCS by laparoscopic extravesical transperitoneal approach (LETA) following Lich
      Gregoir technique. The aim of this study was to describe the evolution and
      evaluate the results and benefits of this technique. MATERIALS AND METHODS:
      Between August 2007 and January 2010, 60 renal units in 43 children with VUR and
      deterioration of renal function on isotope renography were treated with LETA
      following the Lich-Gregoir procedure. Twelve patients had refluxing DCS in a
      lower polar system; three of them had bilateral VUR. Three cases of refluxing DCS
      were associated to obstruction. Two of them presented an ectopic ureterocele with
      adequate split renal function and another had an ectopic ureterocele with
      complete deterioration of upper polar renal function. Their mean age was 36
      months (range: 15-80 months). RESULTS: The mean surgical time was 90 minutes (38
      140 minutes) in unilateral and 144 minutes (120-200 minutes) in bilateral VUR
      including cystoscopy. All procedures were successfully completed laparoscopically
      and the reflux was corrected in all patients. One-stage laparoscopic
      heminephroureterectomy with excision of ureterocele and ureteric reimplantation
      was done in 1 case, and ureterocele excision and ureteric reimplantation by LETA
      were done in 2 cases. The mean hospital stay was 27 hours. A cystogram was
      performed systematically in all patients at 45 days postoperatively; none of them
      presented recurrence of VUR. The follow-up period was 11 months (range: 2-24
      months), without recurrence of VUR. CONCLUSION: LETA following the Lich-Gregoir
      procedure in refluxing DCS is a safe and effective approach even in unilateral,
      bilateral simultaneous, and split renal function in duplicated systems. When
      refluxing DCS is associated with obstruction and total deterioration of upper
      polar function, heminephroureterectomy with excision of ureterocele and ureteric
      reimplantation can be safely and effectively performed in a single-stage
      laparoscopic procedure, which minimizes the hazards of traditional open surgical
      reconstruction. A shorter hospital stay, decreased postoperative discomfort,
      reduced recovery period, and a low morbidity to resolve VUR in DCS are the
      benefits of this technique, with success rates similar to the open technique.

PMID- 21190483
TI  - New insights into the role of RNase L in innate immunity.
AB  - The interferon (IFN)-inducible 2'-5'-oligoadenylate synthetase (OAS)/RNase L
      pathway blocks infections by some types of viruses through cleavage of viral and
      cellular single-stranded RNA. Viruses induce type I IFNs that initiate signaling
      to the OAS genes. OAS proteins are pathogen recognition receptors for the viral
      pathogen-associated molecular pattern, double-stranded RNA. Double-stranded RNA
      activates OAS to produce p(x)5'A(2'p5'A)(n); x = 1-3; n > 2 (2-5A) from ATP. Upon
      binding 2-5A, RNase L is converted from an inactive monomer to a potently active
      dimeric endoribonuclease for single-stranded RNA. RNase L contains, from N- to C
      terminus, a series of 9 ankyrin repeats, a linker, several protein kinase-like
      motifs, and a ribonuclease domain homologous to Ire1 (involved in the unfolded
      protein response). In the past few years, it has become increasingly apparent
      that RNase L and OAS contribute to innate immunity in many ways. For example,
      small RNA cleavage products produced by RNase L during viral infections can
      signal to the retinoic acid-inducible-I like receptors to amplify and perpetuate
      signaling to the IFN-beta gene. In addition, RNase L is now implicated in
      protecting the central nervous system against viral-induced demyelination. A role
      in tumor suppression was inferred by mapping of the RNase L gene to the
      hereditary prostate cancer 1 (HPC1) gene, which in turn led to discovery of the
      xenotropic murine leukemia-related virus. A broader role in innate immunity is
      suggested by involvement of RNase L in cytokine induction and endosomal pathways
      that suppress bacterial infections. These newly described findings about RNase L
      could eventually provide the basis for developing broad-spectrum antimicrobial
      drugs.

PMID- 21190485
TI  - Gender differences in HIV drug resistance mutations and virological outcome.
AB  - BACKGROUND: Previous studies have shown that female gender has higher odds of
      developing HIV drug resistance mutations. We aimed to evaluate the gender
      differences in HIV drug resistance mutation patterns and outcomes in a cohort of
      an HIV-infected population who underwent genotype resistance testing (GRT).
      METHODS: We conducted a retrospective study from January 2004 to April 2007 of
      patients >12 years of age who underwent GRT in the HIV Outpatient Program Clinic
      (HOP) at the Medical Center of Louisiana at New Orleans. RESULTS: Among 391
      patients included in the analysis, 130 were females and 261 were males. There
      were no major statistically significant differences in the baseline demographic,
      clinical, or genotypic characteristics between males and females before GRT
      except for race, presence of coexisting hepatitis B and C infection, prior
      diagnosis of tuberculosis, presence of thymidine analogue mutations (TAMs), and
      protease inhibitor (PI) mutations L90M and I84V (p < 0.05). Females showed a 1.6
      fold probability of carrying nonnucleoside reverse transcriptase inhibitor
      (NNRTI) mutations (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.02-2.6),
      whereas males showed a 2-fold probability of carrying PI mutations (OR 2, 95% CI
      1.12-3.8). Sixty-seven percent of males achieved virological suppression compared
      with 57% of females at 1 year (+/-6 months). Independent of history of optimal
      treatment and race, females showed 2-fold odds of having virological failure
      compared with males at 1 year (+/-6 months) after GRT (OR 2.0, 95% CI 1.04-3.8).
      CONCLUSIONS: Females did worse than males in regard to viral load suppression at
      the end of 1 year if they had documented HIV drug resistance at baseline. Further
      longitudinal studies are needed to confirm our findings.

PMID- 21190484
TI  - Patient-centered care for Muslim women: provider and patient perspectives.
AB  - OBJECTIVE: The purpose of this study was twofold: (1) to address the gap in
      existing literature regarding provider perspectives about provision of high
      quality, culturally appropriate, patient-centered care to Muslim women in the
      United States and (2) to explore congruence between provider and patient
      perceptions regarding barriers to and recommendations for providing such care.
      METHODS: Using a cross-sectional study design, a written survey was administered
      to a convenience sample of healthcare providers (n = 80) and Muslim women (n =
      27). RESULTS: There was considerable congruence among patients and providers
      regarding healthcare needs of Muslim women. A majority (83.3%) of responding
      providers reported encountering challenges while providing care to Muslim women.
      A majority (93.8%) of responding patients reported that their healthcare provider
      did not understand their religious or cultural needs. Providers and patients
      outlined similar barriers/challenges and recommendations. Key challenges included
      lack of providers' understanding of patients' religious and cultural beliefs;
      language-related patient-provider communication barriers; patients' modesty
      needs; patients' lack of understanding of disease processes and the healthcare
      system; patients' lack of trust and suspicion about the healthcare system,
      including providers; and system-related barriers. Key recommendations included
      provider education about basic religious and cultural beliefs of Muslim patients,
      provider training regarding facilitation of a collaborative patient-provider
      relationship, addressing language-related communication barriers, and patient
      education about disease processes and preventive healthcare. CONCLUSIONS: Both
      providers and patients identify significant barriers to the provision of
      culturally appropriate care to Muslim women. Improving care would require a
      flexible and collaborative care model that respects and accommodates the needs of
      patients, provides opportunities for training providers and educating patients,
      and makes necessary adjustments in the healthcare system. The findings of this
      study can guide future research aimed at ensuring high-quality, culturally
      appropriate, patient-centered healthcare for Muslim women in the United States
      and other western countries.

PMID- 21190486
TI  - Positive effects of the non-pneumatic anti-shock garment on delays in accessing
      care for postpartum and postabortion hemorrhage in Egypt and Nigeria.
AB  - BACKGROUND: We examined whether the non-pneumatic anti-shock garment (NASG)
      ameliorates the effects of delays in transport to and treatment at hospitals for
      women with postpartum hemorrhage (PPH) and postabortion hemorrhage (PAH) and
      investigated the effects of NASG use on timing of delivery of interventions in
      hospital. METHODS: Pre/post studies of the NASG were conducted at hospitals in
      Cairo (n = 349 women), Assuit (n = 274), Southern Nigeria (n = 57), and Northern
      Nigeria (n = 124). In post-hoc analyses, comparisons of delays were conducted
      using analysis of variance (ANOVA), and associations of delays with extreme
      adverse outcomes (EAO, mortality or severe morbidity) were examined using chi
      square tests, odds ratios (ORs), and multivariate logistic regression. RESULTS:
      Median minutes from hemorrhage start to study admission differed by site, ranging
      from 15 minutes in Cairo to 225 minutes in Northern Nigeria (p < 0.001). Median
      minutes from study admission to blood transfusion ranged from 30 minutes in Cairo
      to 209 minutes in Southern Nigeria (p < 0.001). Twenty percent of women with >=60
      minutes between hemorrhage start and study admission experienced an EAO without
      the NASG compared with only 6% with the NASG (chi(2) = 13.71, p < 0.001). In
      hospital delays in receiving intravenous (IV) fluids and blood were more common
      in the NASG phase. CONCLUSIONS: Women with PPH or PAH in Egypt and Nigeria often
      face delays in reaching emergency obstetrical care facilities and delays in
      receiving definitive therapies after arrival. Our results indicate that the NASG
      can reduce the impact of these delays. Stabilization does not replace treatment,
      however, and delays in fluid/blood administration with NASG use must be avoided.

PMID- 21190488
TI  - Accruing evidence for a beneficial role of pneumatic biocompression in
      lymphedema.

PMID- 21190487
TI  - Interferon-stimulated gene 15 and the protein ISGylation system.
AB  - Interferon-stimulated gene 15 (ISG15) is one of the most upregulated genes upon
      Type I interferon treatment or pathogen infection. Its 17  kDa protein product,
      ISG15, was the first ubiquitin-like modifier identified, and is similar to a
      ubiquitin linear dimer. As ISG15 modifies proteins in a similar manner to
      ubiquitylation, protein conjugation by ISG15 is termed ISGylation. Some of the
      primary enzymes that promote ISGylation are also involved in ubiquitin
      conjugation. The process to remove ISG15 from its conjugated proteins, termed de
      ISGylation, is performed by a cellular ISG15-specific protease, ubiquitin
      specific proteases with molecular mass 43 kDa (UBP43)/ubiquitin-specific
      proteases 18. Relative to ubiquitin, the biological function of ISG15 is still
      poorly understood, but ISG15 appears to play important roles in various
      biological and cellular functions. Therefore, there is growing interest in ISG15,
      as the study of free ISG15 and functional consequences of ISGylation/de
      ISGylation may identify useful therapeutic targets. This review highlights recent
      discoveries and remaining questions important to understanding the biological
      functions of ISG15.

PMID- 21190489
TI  - Lymphatic pump treatment augments lymphatic flux of lymphocytes in rats.
AB  - BACKGROUND: Lymphatic pump techniques (LPT) are used by osteopathic practitioners
      for the treatment of edema and infection; however, the mechanisms by which LPT
      enhances the lymphatic and immune systems are poorly understood. METHODS AND
      RESULTS: To measure the effect of LPT on the rat, the cisterna chyli (CC) of 10
      rats were cannulated and lymph was collected during 4 min of 1) pre-LPT baseline,
      2) 4 min LPT, and 3) 10 min post-LPT recovery. LPT increased significantly (p <
      0.05) lymph flow from a baseline of 24 +/- 5 MUl/min to 89 +/- 30 MUl/min. The
      baseline CC lymphocyte flux was 0.65 +/- 0.21 * 106 lymphocytes/min, and LPT
      increased CC lymphocyte flux to 6.10 +/- 0.99 * 106 lymphocytes/min (p < 0.01).
      LPT had no preferential effect on any lymphocyte population, since total
      lymphocytes, CD4+ T cells, CD8+ T cells, and B cell numbers were similarly
      increased. To determine if LPT mobilized gut-associated lymphocytes into the CC
      lymph, gut-associated lymphocytes in the CC lymph were identified by staining CC
      lymphocytes for the gut homing receptor integrin alpha4beta7. LPT significantly
      increased (p < 0.01) the flux of alpha4beta7 positive CC lymphocytes from a
      baseline of 0.70 +/- 0.03 * 105 lymphocytes/min to 6.50 +/- 0.10 * 105
      lymphocytes/min during LPT. Finally, lymphocyte flux during recovery was similar
      to baseline, indicating the effects of LPT are transient. CONCLUSIONS:
      Collectively, these results suggest that LPT may enhance immune surveillance by
      increasing the numbers of lymphocytes released in to lymphatic circulation,
      especially from the gut associated lymphoid tissue. The rat provides a useful
      model to further investigate the effect of LPT on the lymphatic and immune
      systems.

PMID- 21190490
TI  - Long-distance transportation of live isolated lymphatic vessels.
AB  - BACKGROUND: We performed experiments to test whether isolated lymphatic vessels
      would remain viable after overnight long-distance shipment. METHODS AND RESULTS:
      Freshly isolated segments of rat mesenteric lymphatic vessels were placed into
      tubes filled by chilled D-MEM/F12 supplemented with antibiotics and shipped via
      overnight by express mail from College Station, TX to Columbia, MO. Standard
      physiological and pharmacological tests were performed to investigate the
      influence of the long-distance transport procedure on the spontaneous
      contractility of isolated, cannulated, and pressurized rat mesenteric lymphatic
      vessels. The results demonstrate that normal contractile function of isolated
      lymphatic vessels can be preserved with long-distance shipping and subsequent
      overnight recovery if the proper precautions are taken. CONCLUSIONS: The method
      of lymphatic vessel transportation described in this report opens up the
      opportunity to perform in vitro functional tests on lymphatic tissues harvested
      and initially processed in a remote location. In addition, the described
      procedures may expand the options for potential sources of fresh human tissue,
      harvested during surgery or autopsy and allowed to be available to lymphatic
      researchers in remote locations.

PMID- 21190491
TI  - Postural effect on the size of the cisterna chyli.
AB  - BACKGROUND: The aim was to investigate the effect of patient position on the size
      of the cisterna chyli using positional MRI. The cisterna chyli is usually the
      only large lymphatic vessel that can be found on cross-sectional imaging. Not
      much is known about its postural behavior. However, animal studies suggest that
      the cisterna chyli varies in size according to physical activity. METHODS AND
      RESULTS: Retrospectively, 998 MRI scans of patients referred for positional MRI
      were reviewed. Ten patients had acquired axial scans in at least two positions at
      the level T12/L1 or/and L1/2 and were included in the study. The area
      representing the cisterna chyli was assessed on axial images and its size was
      compared in different positions. The size of the cisterna chyli determined as the
      cross-sectional area was 14.7 mm2 +/- 17.3 mm2 in the supine position, 43.8 mm2
      +/- 3.1 mm2 in the sitting position, and 62.9 mm2 +/- 42.5 mm2 in the standing
      position. Using the t-test, a statistically significant difference was found in
      the size of the cistern chyli between supine and standing positions and between
      supine and sitting positions. CONCLUSIONS: The size of the cisterna chyli shows
      postural variations. This finding is discussed in regards to possible
      implications of interventional procedures in the thoracic duct. Physicians
      reading MR images acquired in positions other than supine should be aware of
      these physiological changes.

PMID- 21190492
TI  - The disappearance of subpleural and interlobular lymphatics in idiopathic
      pulmonary fibrosis.
AB  - BACKGROUND: The lymphatics in the interlobular and subpleural parenchyma
      contribute to alveolar clearance in the lung, but the information on the
      remodeling of these lymphatics is quite limited in idiopathic pulmonary fibrosis
      lungs that contain severe fibrosis in these regions. We compared the alteration
      of these lymphatics and lymphangiogenesis among idiopathic pulmonary fibrosis and
      nonfibrotic interstitial pneumonias with a better prognosis. METHODS AND RESULTS:
      The lung tissue specimens of eighteen patients with idiopathic pulmonary fibrosis
      (ten surgical biopsies and eight autopsies), six with organizing pneumonia, six
      with cellular nonspecific interstitial pneumonia, and five normal controls were
      examined by morphometric analysis of the lymphatics identified by
      immunohistochemistry. In addition, three-dimensional reconstruction of
      lymphatics, apoptosis of lymphatic endothelial cells and the cells producing
      growth factors for lymphangiogenesis were also evaluated. Both the subpleural and
      the interlobular lymphatics in idiopathic pulmonary fibrosis lungs were
      significantly decreased in the severe fibroconnective lesions, with rare
      lymphangiogenesis. The three-dimensional images of the subpleural lymphatics in
      idiopathic pulmonary fibrosis clearly revealed destruction by fibrosis; apoptosis
      was observed in these lymphatic endothelial cells. In contrast, organizing
      pneumonia and cellular nonspecific interstitial pneumonia preserved these
      lymphatics, and active lymphangiogenesis occurred in the alveolar lesions.
      CONCLUSIONS: These results reveal severe damage of the subpleural and
      interlobular lymphatics in idiopathic pulmonary fibrosis lungs, and suggest
      impaired alveolar clearance as another pathogenesis of its refractoriness.

PMID- 21190493
TI  - Advanced pneumatic therapy in self-care of chronic lymphedema of the trunk.
AB  - BACKGROUND: The purpose of this study was to conduct a preliminary, post-market,
      home study of the Flexitouch((r)) system to examine the potential efficacy of the
      device as a component of self-care in breast cancer survivors with truncal
      lymphedema. METHODS AND RESULTS: A quasi-experimental, pre-treatment, post
      treatment design was used. Twelve participants received a total of ten self
      administered, consecutive, one hour per day treatments. Treatments one and two
      were observed by study staff and the remaining eight were unobserved. Assessments
      were conducted at baseline, after the first two treatments, mid-way through
      therapy, and at the end-of-study. Logs revealed 100% compliance with the eight
      prescribed unobserved home treatments. Symptoms were assessed by self-report
      symptom surveys. Signs, objectively observed physical phenomenon, were assessed
      by staff-initiated skin examination and circumferential truncal measurements.
      Statistically significant improvement in truncal symptoms and sleep were found.
      Changes in function and girth were not statistically significant in this initial
      study. CONCLUSIONS: Breast cancer survivors with truncal lymphedema may benefit
      from using an advanced pneumatic compression devices with truncal treatment as
      part of their self-care program. Participants were highly compliant in device
      use. Further research of this intervention is warranted. To facilitate future
      research, clinically meaningful reductions in truncal girth should be defined.

PMID- 21190496
TI  - Will blood tell? Three recent articles demonstrate genetic selection in Tibetans.

PMID- 21190500
TI  - Acetazolamide and sulfonamide allergy: a not so simple story.
AB  - Allergies and adverse reactions to sulfonamide medications are quite common. Two
      distinct categories of drugs are classified as sulfonamides: antibiotics and
      nonantibiotics. The two groups differ in their chemical structure, use, and the
      rate at which adverse reactions occur. Cross-reactivity between the two groups
      has been implied in the past, but is suspect. Acetazolamide, from the
      nonantibiotic group, is routinely used in the prevention and treatment of high
      altitude issues and may not need to be avoided in individuals with a history of
      sulfonamide allergy. This review addresses the differences between the groups and
      the propensity for intergroup and intragroup adverse reactions based on the
      available literature. We also examine the different clinical presentations of
      allergy and adverse reactions, from simple cutaneous reactions with no sequelae
      through Stevens-Johnson syndrome and anaphylaxis, with risk for significant
      morbidity and mortality. We offer a systematic approach to determine whether
      acetazolamide is a safe option for those with a history of allergy to
      sulfonamides.

PMID- 21190501
TI  - Prediction of acute mountain sickness by monitoring arterial oxygen saturation
      during ascent.
AB  - Acute mountain sickness (AMS) is a common problem while ascending at high
      altitude. AMS may progress rapidly to fatal results if the acclimatization
      process fails or symptoms are neglected and the ascent continues. Extensively
      reduced arterial oxygen saturation at rest (R-Spo2) has been proposed as an
      indicator of inadequate acclimatization and impending AMS. We hypothesized that
      climbers less likely to develop AMS on further ascent would have higher Spo2
      immediately after exercise (Ex-Spo2) at high altitudes than their counterparts
      and that these postexercise measurements would provide additional value for
      resting measurements to plan safe ascent. The study was conducted during eight
      expeditions with 83 ascents. We measured R-Spo2 and Ex-Spo2 after moderate daily
      exercise [50 m walking, target heart rate (HR) 150 bpm] at altitudes of 2400 to
      5300 m during ascent. The Lake Louise Questionnaire was used in the diagnosis of
      AMS. Ex-Spo2 was lower at all altitudes among those climbers suffering from AMS
      during the expeditions than among those climbers who did not get AMS at any
      altitude during the expeditions. Reduced R-Spo2 and Ex-Spo2 measured at altitudes
      of 3500 and 4300 m seem to predict impending AMS at altitudes of 4300 m (p < 0.05
      and p < 0.01) and 5300 m (both p < 0.01). Elevated resting HR did not predict
      impending AMS at these altitudes. Better aerobic capacity, younger age, and
      higher body mass index (BMI) were also associated with AMS (all p < 0.01). In
      conclusion, those climbers who successfully maintain their oxygen saturation at
      rest, especially during exercise, most likely do not develop AMS. The results
      suggest that daily evaluation of Spo2 during ascent both at rest and during
      exercise can help to identify a population that does well at altitude.

PMID- 21190502
TI  - Peripheral blood lymphocytes: a model for monitoring physiological adaptation to
      high altitude.
AB  - Depending on the absolute altitude and the duration of exposure, a high altitude
      environment induces various cellular effects that are strictly related to changes
      in oxidative balance. In this study, we used in vitro isolated peripheral blood
      lymphocytes as biosensors to test the effect of hypobaric hypoxia on seven
      climbers by measuring the functional activity of these cells. Our data revealed
      that a 21-day exposure to high altitude (5000 m) (1) increased intracellular
      Ca(2+) concentration, (2) caused a significant decrease in mitochondrial membrane
      potential, and (3) despite possible transient increases in intracellular levels
      of reactive oxygen species, did not significantly change the antioxidant and/or
      oxidative damage-related status in lymphocytes and serum, assessed by measuring
      Trolox-equivalent antioxidant capacity, glutathione peroxidase activity, vitamin
      levels, and oxidatively modified proteins and lipids. Overall, these results
      suggest that high altitude might cause an impairment in adaptive antioxidant
      responses. This, in turn, could increase the risk of oxidative-stress-induced
      cellular damage. In addition, this study corroborates the use of peripheral blood
      lymphocytes as an easily handled model for monitoring adaptive response to
      environmental challenge.

PMID- 21190503
TI  - The prevalence of and risk factors for acute mountain sickness in the Eastern and
      Western Alps.
AB  - Acute mountain sickness (AMS) is the most common condition of high altitude
      illnesses. Its prevalence varies between 15% and 80% depending on the speed of
      ascent, absolute altitude reached, and individual susceptibility. Additionally,
      we assumed that the more experienced mountaineers of the Western Alps are less
      susceptible to developing AMS than recreational mountaineers of the Eastern Alps
      or tourist populations. Therefore, the main goals of the present study were the
      collection of data regarding the AMS prevalence and triggers in both the Eastern
      and Western Alps using identical methods. A total of 162 mountaineers, 79 in the
      Eastern Alps (3454 m) and 83 in the Western Alps (3817 m) were studied on the
      morning after their first night at high altitude. A diagnosis of AMS was based on
      a Lake Louise Score (LLS) >=4, the presence of headache, and at least one
      additional symptom. Thirty of 79 subjects (38.0%) suffered from AMS at 3454 m in
      the Eastern Alps as did 29 of 83 (34.9%) at 3817 m in the Western Alps. After
      adjustment for altitude, the prevalence in the Western Alps constituted 24.5%,
      which differed significantly (p = 0.04) from that found in the Eastern Alps. The
      lower mountaineering experience of mountaineers in the Eastern Alps turned out to
      be the only factor for explaining their higher AMS prevalence. Thus, expert
      advice by mountain guides or experienced colleagues could help to reduce the AMS
      risk in these subjects.

PMID- 21190504
TI  - Evidence for a genetic basis for altitude illness: 2010 update.
AB  - Altitude illness refers to a group of environmentally mediated pathophysiologies.
      Many people will suffer acute mountain sickness shortly after rapidly ascending
      to a moderately hypoxic environment, and an unfortunate few will develop
      potentially fatal conditions such as high altitude pulmonary edema or high
      altitude cerebral edema. Some individuals seem to be predisposed to developing
      altitude illness, suggesting an innate contribution to susceptibility. The
      implication that there are altitude-sensitive and altitude-tolerant individuals
      has stimulated much research into the contribution of a genetic background to the
      efficacy of altitude acclimatization. Although the effect of altitude attained
      and rate of ascent on the etiology of altitude illness is well known, there are
      only tantalizing, but rapidly accumulating, clues to the genes that may be
      involved. In 2006, we reviewed what was then known about the genetics of altitude
      illness. This article updates that review and attempts to tabulate all the
      available genetic data pertaining to these conditions. To date, 58 genes have
      been investigated for a role in altitude illness. Of these, 17 have shown some
      association with the susceptibility to, or the severity of, these conditions,
      although in many cases the effect size is small or variable. Caution is
      recommended when evaluating the genes for which no association was detected,
      because a number of the investigations reviewed in this article were
      insufficiently powered to detect small effects. No study has demonstrated a clear
      cut altitude illness gene, but the accumulating data are consistent with a
      polygenic condition with a strong environmental component. The genes that have
      shown an association affect a variety of biological pathways, suggesting that
      either multiple systems are involved in altitude pathophysiology or that gene
      gene interactions play a role. Although numerous studies have been performed to
      investigate specific genes, few have looked for evidence of heritability or
      familial transmission, or for epidemiological patterns that would be consistent
      with genetically influenced conditions. Future trends, such as genome-wide
      association studies and epigenetic analysis, should lead to enhanced
      understanding of the complex interactions within the genome and between the
      genome and hypoxic environments that contribute to an individual's capacity to
      acclimatize rapidly and effectively to altitude.

PMID- 21190505
TI  - 17 degrees Celsius body temperature--resuscitation successful?
AB  - The resuscitation of patients with accidental profound hypothermia is
      challenging. A 17-year-old man got lost on the first of January, after a New
      Year's Eve party in the foothills of the Alps. After a search of four hours, he
      was found unconscious with fixed pupils, a Glasgow Coma Scale of three points,
      and a body temperature below 20 degrees  Celsius. There were no signs for
      traumatic injuries. Initial electrocardiogram (ECG) showed no heart activity.
      Basic life support was begun by the mountain rescue service and continued by the
      medical helicopter team. The patient was transferred under continuous cardiac
      massage, airway management with intubation and intravenous line via external
      jugular vein by helicopter to the nearest hospital for analysis of serum
      potassium. Body temperature was 17 degrees C measured by urinary bladder
      electronic thermometer. The serum potassium was 7.55 mmol/L, therefore the
      patient was transferred by helicopter to the next cardiovascular center for
      rewarming with extracorporal circulation (ECC). Under the rewarming process with
      ECC, the heart activity restarted at 25 degrees C with external defibrillation.
      The patient was rewarmed to 37.2 degrees C after four hours of ECC. Cerebral CT
      scans after 24 h and 48 h revealed no significant hypoxia and after extubation
      the early rehabilitation process started. After six weeks, the patient regained
      the ability to walk and started to communicate on a basic level. After 54 days
      the patient presented signs of septic shock. After initial stabilization and CT
      diagnostic, a laparotomy was performed. The intraoperative finding was a total
      necrosis of the small bowel and colon. The patient died on the same day. Post
      mortem examination showed a necrotizing enterocolitis with transmural necrosis of
      the bowel. Survivors of uncontrolled profound hypothermia below 20 degrees C core
      temperature are rare. The epicrisis is often prolonged by complications of
      different causes. The present case reports a necrotizing enterocolitis with a non
      occlusive mesenteric ischemia (NOMI) as a medium-term complication of profound
      hypothermia.

PMID- 21190506
TI  - Experience with helicopter rescue missions for crevasse accidents.
AB  - We retrospectively studied incidence, patterns, and severity of injury and
      hypothermia in 95 victims of crevasse accidents. Fifteen (16%) victims were
      already dead when the rescue team arrived on the scene. Asphyxia (8 victims) was
      typically caused by snow burial owing to a collapse of snow bridges covering
      crevasses and was observed only during winter sports activities on glaciers. In 7
      patients, death was caused by lethal trauma. Severe or critical multisystem
      trauma (ISS >= 16) was found in an additional 16 victims (17%). Severe or
      critical injuries were predominantly thoracic injuries and injuries of the
      extremities and/or pelvic region. Severe accidental hypothermia was observed in 9
      of the 95 victims (10%). Three of these suffered from hypothermic sudden cardiac
      arrest during rescue and were immediately evacuated with ongoing CPR; all 3 made
      a full recovery after extracorporeal rewarming. More than two-thirds of all
      victims were still trapped in the crevasse when the rescue team arrived. However,
      the majority of them could be relatively easily extricated using standard
      mountaineering equipment and improvised rescue techniques. Prolonged and
      difficult extrication efforts were needed in less than 10% of victims. Summing
      up, trauma and asphyxia are the most important causes of mortality and acute life
      threatening medical problems in this study, but asphyxia will be far less common
      in mountain regions offering fewer glacier sport activities in the winter months.
      Hypothermic sudden cardiac arrest could not be prevented during the difficult
      conditions of crevasse extrication in one-third of all hypothermic victims;
      however, prognosis was excellent with advanced life support at the scene and
      immediate helicopter evacuation to extracorporeal rewarming.

PMID- 21190507
TI  - The VIIIth World Congress of High Altitude Medicine and Physiology, Arequipa,
      Peru, August 8-12, 2010.

PMID- 21190508
TI  - Comparison of the fine structure processing (FSP) strategy and the CIS strategy
      used in the MED-EL cochlear implant system: speech intelligibility and music
      sound quality.
AB  - OBJECTIVE: The aim of the present study was to evaluate MED-EL's Fine Structure
      Processing (FSP) strategy in comparison with their variations of the standard
      Continuous Interleaved Sampling (CIS) strategy denoted CIS+ and High Definition
      CIS (HDCIS). STUDY SAMPLE: Twenty experienced adult CI users participated in the
      study in connection with upgrading to a new speech processor and at a two-year
      follow-up. DESIGN: Blinded paired-comparisons between FSP and HDCIS were
      performed for speech intelligibility and music sound quality. Standard speech
      recognition tests in quiet and in noise were also accomplished to monitor the
      participants' actual performance and to evaluate long-term outcomes. RESULTS:
      Overall, the paired-comparison results showed no significant differences between
      the strategies, however, the total numbers of significant individual preferences
      were: 11 FSP vs. 12 HDCIS for speech, and 4 FSP vs. 15 HDCIS for music. The
      average speech recognition score decreased significantly after one month with
      FSP, but after two years there were no significant difference compared to the
      initial results with CIS+. CONCLUSIONS: Owing to the large individual differences
      in subjective preference, and the fact that the FSP strategy was not superior to
      the CIS variations, the recipients should be given the opportunity of choosing
      between the strategies

PMID- 21190509
TI  - Screening for mutations in the phosphatidylinositol 4-kinase 2-alpha gene in
      autosomal recessive hereditary spastic paraplegia.
AB  - Numerous genes causing autosomal recessive hereditary spastic paraplegia (AR HSP)
      have been described. Despite this, in many families the causative gene and
      mutation are unknown. In this study we sequenced the Pi4k2a gene, whose knockout
      has been shown to cause a typical HSP model in mice, in 24 index cases of
      autosomal recessive HSP not known to be linked to any other HSP locus. No
      pathogenic changes were identified in exons or splice sites, suggesting the
      Pi4k2a gene may not be a cause of AR HSP in humans.

PMID- 21190510
TI  - Gefitinib versus docetaxel in previously treated advanced non-small-cell lung
      cancer: a meta-analysis of randomized controlled trials.
AB  - PURPOSE: A meta-analysis of randomized controlled trials was performed to compare
      the efficacy, quality of life (QOL), symptom improvement and toxicities of
      gefitinib with docetaxel in previously treated advanced non-small-cell lung
      cancer. METHODS: The PubMed database, the Cochrane Library and references of
      published trials were searched. Two reviewers independently assessed the quality
      of the trials and extracted data. The hazard ratios (HRs) for overall survival
      (OS) and progression-free survival (PFS), relative risks (RRs) for overall
      response rate, QOL and symptom improvement, and odds ratios (ORs) for main
      toxicities were pooled using STATA package. RESULTS: Four multicenter, randomized
      controlled trials involving 2257 patients with previously treated advanced NSCLC
      were ultimately analyzed. The pooled HRs showed no significant difference in OS
      and PFS between the two groups (HR = 1.02, 95% CI = 0.92-1.12, p = 0.70; HR =
      0.97, 95% CI = 0.88-1.07, p = 0.57, respectively). Gefitinib significantly
      improved overall response rate (RR = 1.58, 95% CI = 1.02-2.45, p = 0.04) and QOL
      (RR = 1.55, 95% CI = 1.27-1.88, p = 0.00 by Functional Assessment of Cancer
      Therapy-Lung and RR = 1.86, 95% CI = 1.43-2.42, p = 0.00 by Trial Outcome Index,
      respectively). Gefitinib had fewer grade 3 or 4 neutropenia and fatigue (OR =
      0.02, 95% CI = 0.01-0.03, p = 0.00; and OR = 0.47, 95% CI = 0.32-0.70, p = 0.00,
      respectively), but more grade 3 or 4 rash (OR = 2.87, 95% CI = 1.24-6.63, p =
      0.01) than docetaxel. The grade 3 or 4 nausea, vomiting and diarrhea and symptom
      improvement were comparable between the two drugs. CONCLUSIONS: In conclusion,
      although similar OS and PFS, gefitinib showed an advantage over docetaxel in
      terms of objective response rate, QOL and tolerability. Therefore, gefitinib is
      an important and valid treatment option for previously treated advanced non-small
      cell lung cancer patients.

PMID- 21190511
TI  - Changes in fibrin D-dimer, fibrinogen, and protein S during pregnancy.
AB  - BACKGROUND: Pregnancy is a hypercoagulable state with a 5- to 10- fold higher
      risk of venous thromboembolism. Existing reference intervals for fibrin D-dimer
      (D-dimer), functional fibrinogen (fibrinogen) and protein S, free antigen
      (protein S) are based on non-pregnant patients and reference intervals for
      pregnant patients are warranted. Objectives. The aim of the present study was to
      contribute to the establishment of reference intervals for D-dimer, fibrinogen
      and protein S during pregnancy and to discuss the use of the analyses during
      pregnancy. METHODS: We included 55 healthy pregnant women in gestational week 11
      17, with normal current pregnancy. Blood samples were collected in gestational
      weeks 11-17, 21-27 and 34-37. The three plasma parameters D-dimer, fibrinogen and
      protein S were analysed by STA-R Evolution(r). RESULTS: A significant rise in D
      dimer was found from first to second trimester (p < 0.0001) and from second to
      third trimester (p < 0.0001). The level of fibrinogen rose significantly from
      second to third trimester (p < 0.0001). Protein S showed a statistically
      significant fall in the level from first to second trimester (p < 0.0001) and
      remained stable thereafter. CONCLUSION: Changes during pregnancy in plasma D
      dimer, protein S and fibrinogen were confirmed. Further clinical studies are
      needed to clarify a clinical useful cut-off point for D-dimer in pregnancy. We
      suggest careful attention to a low peripartum fibrinogen, since it indicates an
      increased bleeding risk. We confirmed an earlier suggested lower cut-off point
      for protein S, during pregnancy.

PMID- 21190512
TI  - IL-6 has no acute effect on the regulation of urea synthesis in vivo in rats.
AB  - BACKGROUND: Clinical or experimentally induced, active inflammation up-regulates
      the in vivo capacity of urea synthesis (CUNS), which promotes nitrogen removal
      from the body and metabolic catabolism. We have shown that tumor necrosis factor
      alpha (TNF-alpha) up-regulates CUNS and increases interleukin 6 expression (IL-6)
      within hours of administration. The described effect of TNF-alpha on nitrogen
      homeostasis may, therefore, depend on IL-6. METHODS: Three hours after the i.v.
      injection of 125 MUg.kg-1 of IL-6 or placebo, we evaluated the CUNS, hepatocyte
      urea cycle enzyme protein levels and the mRNA levels of the urea cycle enzyme
      genes in rats. The prevailing rat serum acute phase proteins and their liver mRNA
      levels were also measured. RESULTS: IL-6 did not change CUNS or hepatocyte urea
      cycle enzyme protein levels, whereas urea cycle enzyme mRNA levels, except for
      ornithine transcarbamylase (OTC), decreased by approximately 20%. The liver mRNA
      levels of alpha2MG, haptoglobin and alpha1AGP all increased by 1.5- to 2-fold (p
      < 0.001). In serum, only the alpha2MG concentration slightly increased (p <
      0.001), whereas the levels of the other circulating acute phase proteins remained
      unchanged. CONCLUSION: IL-6 is not the mediator of the in vivo CUNS up-regulation
      observed 3 h after TNF-alpha administration, but it may be involved in the down
      regulation of urea cycle genes. IL-6 may also mediate TNF-alpha effects on acute
      phase protein gene expression. Thus, IL-6 did not contribute to the in vivo
      hepatic component of inflammation-associated catabolism.

PMID- 21190520
TI  - ?

PMID- 21190513
TI  - Whole-cell biochips for bio-sensing: integration of live cells and inanimate
      surfaces.
AB  - Recent advances in the convergence of the biological, chemical, physical, and
      engineering sciences have opened new avenues of research into the interfacing of
      diverse biological moieties with inanimate platforms. A main aspect of this
      field, the integration of live cells with micro-machined platforms for high
      throughput and bio-sensing applications, is the subject of the present review.
      These unique hybrid systems are configured in a manner that ensures positioning
      of the cells in designated patterns, and enables cellular viability maintenance,
      and monitoring of cellular functionality. Here we review both animate and
      inanimate surface properties and how they affect cellular attachment, describe
      relevant modifications of both types of surfaces, list technologies for platform
      engineering and for cell deposition in the desired configurations, and discuss
      the influence of various deposition and immobilization methods on the viability
      and performance of the immobilized cells.

PMID- 21190522
TI  - MIIP, a cytoskeleton regulator that blocks cell migration and invasion, delays
      mitosis, and suppresses tumorogenesis.
AB  - The migration and invasion inhibitory protein (MIIP) was initially discovered in
      a yeast two-hybrid screen for proteins that interact and inhibit the migration
      and invasion-promoting protein insulin-like growth factor binding protein 2
      (IGFBP2). Recent studies have shown that MIIP not only modulates IGFBP2 but also
      regulates microtubule by binding to and inhibiting HDAC6, a class 2 histone
      deacetylase that deacetylates alpha-tubulin, heat-shock protein 90 (HSP90), and
      cortactin. In addition, MIIP also regulates the mitosis checkpoint, another
      microtubule-associated process. The location of the MIIP gene in chromosomal
      region 1p36, a commonly deleted region in a broad spectrum of human cancers, and
      the observation that MIIP attenuates tumorigenesis in a mouse model suggest that
      it functions as a tumor-suppressor gene. This review summarizes the recent
      progress in characterizing this novel protein, which regulates cell migration and
      mitosis, two processes that rely on the highly coordinated dynamics of the
      microtubule and cytoskeleton systems.

PMID- 21190523
TI  - Rab5 in the regulation of cell motility and invasion.
AB  - Cellular invasion requires careful regulation of the cell migration and apoptotic
      signaling cascades, allowing cell movement and survival of the emigrating
      populations. Components of the endosomal machinery are involved in these
      processes, and in particular the role of small GTPases of the Rab family has
      become appreciated. Rab5 is best known for its role in regulating the trafficking
      of early endosomes, however, it has recently been appreciated to associate with
      and regulate the routing of complexes containing integrins, the primary cellular
      receptors for the extracellular matrix. The association regulates the spatio
      temporal activation of signals of downstream growth factors and integrins. Rab
      proteins have also been linked to apoptosis mediated by cell surface death
      receptors, which elicit the activation of the death cascade via activation of
      caspase 8. Recently, the link between trafficking, apoptosis and cell migration
      was strengthened, as Rab5 was determined to work in conjunction with caspase 8 in
      promoting tumor cell motility and metastasis by regulating beta1 integrin
      traffic. The capacity to connect and regulate these pathways identifies Rab5 as a
      key player in future studies of cell migration and tumor dissemination.

PMID- 21190524
TI  - The HGF-met signaling axis: emerging themes and targets of inhibition.
AB  - The Met tyrosine kinase receptor is the only known receptor for hepatocyte growth
      factor (HGF). Downstream Met signaling is essential for embryonic development;
      however, aberrant Met signaling promotes tumor progression by facilitating cell
      proliferation, survival, migration, invasion, and metastasis. Tumor cell invasion
      is considered an important step in distant metastatic foci formation. Several
      recent reviews have focused on the pleiotropic effects of Met signaling in both
      tumor cells and in the surrounding stromal cells. This review will summarize the
      currently described mechanisms driving Met induced tumor cell progression and
      invasion, the role played by cells in the tumor stroma, and therapeutic
      approaches to block receptor activity. In addition, this review will also
      highlight two new areas of development: 1) attenuation of Met signaling via
      multiple mechanisms of action targeting tumor cells and cells in the surrounding
      stroma using plant-derived polyphenols and 2) the induction by HGF of atypical
      lysosome trafficking, leading to increased protease secretion and tumor cell
      invasion. These new areas of research will help to uncover novel therapeutic
      targets to block the HGF/Met signaling axis to slow cancer progression.

PMID- 21190521
TI  - Role of mTOR signaling in tumor cell motility, invasion and metastasis.
AB  - Tumor cell migration and invasion play fundamental roles in cancer metastasis.
      The mammalian target of rapamycin (mTOR), a highly conserved and ubiquitously
      expressed serine/threonine (Ser/Thr) kinase, is a central regulator of cell
      growth, proliferation, differentiation and survival. Recent studies have shown
      that mTOR also plays a critical role in the regulation of tumor cell motility,
      invasion and cancer metastasis. Current knowledge indicates that mTOR functions
      as two distinct complexes, mTORC1 and mTORC2. mTORC1 phosphorylates p70 S6 kinase
      (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1),
      and regulates cell growth, proliferation, survival and motility. mTORC2
      phosphorylates Akt, protein kinase C alpha (PKCalpha) and the focal adhesion
      proteins, and controls the activities of the small GTPases (RhoA, Cdc42 and
      Rac1), and regulates cell survival and the actin cytoskeleton. Here we briefly
      review recent knowledge of mTOR complexes and the role of mTOR signaling in tumor
      cell migration and invasion. We also discuss recent efforts about the mechanism
      by which rapamycin, a specific inhibitor of mTOR, inhibits cell migration,
      invasion and cancer metastasis.

PMID- 21190525
TI  - Role of alpha6beta4 integrin in cell motility, invasion and metastasis of mammary
      tumors.
AB  - Integrin alpha6beta4 is the receptor for the laminin family of extracellular
      matrix proteins and is widely expressed in most epithelial tissues and Schwann
      cells. The expression of this integrin is up-regulated in most epithelial tumors,
      suggesting the role of alpha6beta4 in their progression. The tumor
      microenvironment is also known to enhance the signaling competence of alpha6beta4
      through functional and physical interactions with other receptors. In this
      review, we discuss the biological mechanisms by which integrin alpha6beta4
      promotes carcinoma cell motility and invasion that leads to mammary tumor
      progression.

PMID- 21190526
TI  - Focal adhesion kinase: from in vitro studies to functional analyses in vivo.
AB  - Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that has been shown
      to have key roles in cell migration, proliferation and survival. FAK activity can
      be stimulated in response to several types of extracellular ligands, including
      components of the extracellular matrix and growth factors, suggesting that FAK is
      an important integrator of multiple cues in the extracellular milieu. Recently,
      major progress has been made in understanding the molecular mechanisms regulating
      FAK activity. In particular, several novel proteins have been identified that can
      bind to FAK and inhibit its activity and associated cellular functions, including
      cell motility and invasion. Consistent with its critical functions in signal
      transduction, FAK also plays a pivotal role in mouse development. The
      inactivation of FAK in mice results in embryonic lethality around E8.5; this
      early embryonic lethal phenotype limits the use of the FAK total knockout mouse
      model for studying FAK function in later embryonic development stages and in
      adult mice. To overcome this problem, three independent groups created FAK/flox
      mice and generated several different FAK tissue-specific knockout mice models.
      Here we summarize the progress that has been made regarding the regulation of FAK
      mediated signaling events in cell-based systems and also highlight the in vivo
      functions of FAK in a number of terminally differentiated cell lineages,
      including vascular endothelial cells, cardiomyocytes, neuronal cells,
      keratinocytes and several cancerous cell types.

PMID- 21190527
TI  - PP2A in the regulation of cell motility and invasion.
AB  - Cell motility is a very critical phenomenon that plays an important role in the
      development of eukaryotic organisms. One of the well studied cell motility
      phenomena is chemotaxis, which is described as a directional movement of cell in
      response to changes in external chemotactic gradient. Numerous studies conducted
      both in unicellular organism and in mammalian cells have demonstrated the
      importance of phosphatidylionositol-3 kinase (PI3K) in this process. In addition,
      it is now well established that although PI3K plays an activation role in
      chemotaxis, the role of phosphatases is also critical to maintain this dynamic
      cyclical process. Protein phosphatase 2A (PP2A) is a major serine/threonine
      phosphatase that is a key player in regulating PI3K signaling. PP2A is abundantly
      and ubiquitously expressed and has been highly conserved during the evolution of
      eukaryotes. PP2A is composed of three protein subunits, A, B, and C. Subunit 'A'
      is a 60-65 kDa structural component, 'C' is a 36-38 kDa catalytic subunit, and
      'B' is a 54-130 kDa regulatory subunit. The core complex of PP2A is comprised of
      the A and C subunits, which are tightly associated and this dimeric core
      complexes with the regulatory B subunit. The B subunit determines the substrate
      specificity as well as the spatial and temporal functions of PP2A. PP2A plays an
      important role in regulating multiple signal transduction pathways, including
      cell-cycle regulation, cell-growth and development, cytoskeleton dynamics, and
      cell motility. This review focuses on the role of PP2A in regulating motility of
      normal and transformed cells.

PMID- 21190528
TI  - Novel proteins as regulators of cell motility and invasion.

PMID- 21190529
TI  - Liver growth factor promotes the survival of grafted neural stem cells in a rat
      model of Parkinson's disease.
AB  - Neural stem cells (NSCs) with self-renewal and multilineage potential are
      considered good candidates for cell replacement of damaged nerve tissue. Several
      studies have focused on the ability of the neurotrophic factors coadministration
      to improve the efficiency of grafted NSCs. Liver growth factor (LGF) is an
      hepatic mitogen that promotes regeneration of damaged tissues, including brain
      tissue. It has neurogenic activity and has partially restored the nigrostriatal
      dopaminergic system in an experimental model of Parkinson's disease. Present
      results demonstrate that in the dopamine- depleted striatum of 6-hydroxydopamine
      lesioned rats, grafted NSCs retained their ability to differentiate into neurons,
      astrocytes, and oligodendrocytes. NSCs also differentiated into
      microglia/macrophages and endothelial cells. Thus, 23 +/- 5.6% of them were
      inmunoreactive for isolectin IB4, and a small population integrated into blood
      vessels, showing an endothelial-like morphology. Intrastriatal infusion of LGF
      promoted the viability of the implants, and favored their differentiation to an
      endothelial-like phenotype. Moreover, LGF infusion raised the expression of the
      anti-apoptotic protein Bcl-2 by 3.9 +/- 0.9 fold without affecting the levels of
      the pro-apoptotic protein Bax. Since LGF-treated rats also showed a significant
      reduction in apomorphine-induced rotational behavior, our results suggest that
      administration of this factor might be a convenient treatment for Parkinson's
      disease cell replacement therapies based on NSCs transplantation.

PMID- 21190530
TI  - Effect of human umbilical cord blood progenitor cells versus mononuclear cells on
      acute renal failure rat model.
AB  - BACKGROUND: Acute renal failure (ARF) resulting from ischemic or toxic insults
      remains a major health care problem because of its grave prognosis and the
      limited effectiveness of available treatment modalities. Current treatment
      options for ARF are limited to supportive measures and preventive strategies,
      none of which have been definitively shown to alter mortality. AIM: To assess the
      ability of human umbilical cord blood CD34(+) (HUCB CD34(+)) cells and
      mononuclear (HUCB MNC) cells to improve renal function of nephrotoxic kidney.
      METHODS: ARF was induced in 30 rats by glycerol. After 24 hours, ARF was
      confirmed by increased blood urea nitrogen (BUN), serum urea and creatinine
      levels. The rats were divided into 3 groups, group one included 10 rats treated
      with HUCB CD34(+) cells, group two included 10 rats treated with HUCB MNC and
      group three included 10 rats treated with normal saline. Five rats were included
      in the study as a normal control group. Serial measurement of BUN, serum urea and
      creatinine levels were done every three days throughout the study. To proof
      homing of HUCB CD34(+) into renal tissue, Y chromosome detection in renal tissue
      was carried out using Real time polymerase chain reaction (PCR) technique.
      RESULTS: Four days after the therapy, the renal function of CD34(+) and MNC
      treated rats improved in comparison to saline treated rats. After 2 weeks of
      therapy and at the end of the study (28 days), ANOVA test revealed that, there
      was significant difference between the four studied groups (P=.000). Y
      chromosomes were detected in kidneys of CD34(+) treated rats and MNC treated
      rats. CONCLUSION: HUCB CD34(+) cells and HUCB MNC improve renal function of
      nephrotoxic kidney with superiority to the HUCB MNC.

PMID- 21190532
TI  - Hematopoietic stem cell transplantation for thalassemia.
AB  - Hematopoietic stem cell transplantation (HSCT) represents the only cure for
      patients with thalassemia. At present HSCT in younger patients from an HLA-
      matched sibling donor offers 80% to 87% probability of cure according to risk
      classes. However, results HSCT in adult patients continue to be inferior due to
      advanced of disease. High-resolution tissue typing techniques have enabled
      transplant centres to offer allogeneic HSCT from unrelated donors to patients
      with thalassemia who could not benefit from matched sibling donor transplantation
      with results comparable to those obtained using sibling donors. Advances in
      transplantation biology have made it possible to perform haploidentical HSCT in
      patients with thalassemia who lack a related or unrelated matched donor. Although
      limited number of patients, results of unrelated cord blood transplantation for
      thalassemia are encouraging. Patients with graft failure could now benefit from
      second transplantation using the same donor with a high disease-free survival
      rate. Most ex-thalassemics continue to have disease and treatment-related
      complications acquired before transplantation which require adequate treatment
      following BMT.

PMID- 21190531
TI  - Immunomodulatory activity of mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) were discovered as a rare population of non
      hematopoietic stem cells that reside in the bone marrow and interact closely with
      hematopoietic stem cells to support their growth and differentiation. MSCs are
      multipotent cells that have the ability to differentiate into cells of the
      mesenchymal lineage including adipocytes, osteocytes and chondrocytes and they
      have been reported to home to areas of tissue injury and participate in tissue
      repair. More recently, MSCs have also been described to possess anti-inflammatory
      and immunomodulatory properties that can affect multiple arms of the immune
      system. MSCs have been shown to inhibit T and B cell proliferation, downregulate
      the lytic activity of cytotoxic T lymphocytes and NK cells, inhibit the
      maturation and antigen-presenting function of dendritic cells and modulate
      macrophage function through both contact-dependent and contact-independent
      mechanisms. The administration of MSCs in models of autoimmune disease such as
      collagen-induced arthritis, EAE and autoimmune diabetes has provided additional
      evidence for an immunoregulatory role of MSCs supporting their use in controlling
      autoimmunity. The administration of allogeneic MSCs as immunosuppressive agents
      represents a viable approach as they appear to be largely non-immunogenic and
      clinical trials with allogeneic MSCs are currently underway in graftversus- host
      disease, Crohn's disease and type I diabetes indications. The immunomodulatory
      properties, mechanism of action and potential clinical utility of MSCs are
      reviewed herein.

PMID- 21190533
TI  - Stem cell-based approaches for intervertebral disc regeneration.
AB  - Degeneration of the intervertebral disc is an age-related progressive process
      considered to be the major cause of a series of spine disorders, such as low-back
      pain that affects the majority of adult population and causes a huge loss of time
      from work and medical expenses. Numerous regenerative approaches are being
      developed with the aim to halt or reverse degeneration, including intradiscal
      administration of nucleus pulposus cells and mesenchymal stem cells and anabolic
      growth factors. Each of the currently proposed approaches, however, has exhibited
      certain limitations or shortcomings, largely due to our limited understanding on
      the cell biology, turnover mechanisms of the intervertebral disc as well as the
      etiology of disc degeneration. Intervertebral disc, particularly the central
      nucleus pulposus, is the largest enclosed and avascular tissue in the body and
      owes a microenvironment under high mechanical and osmotic pressures, at severely
      hypoxia, and with very limited nutrient supply. In order to achieve an optimal
      outcome of new regenerative therapies in such a harsh circumstance, identifying
      and characterizing endogenous regenerative properties of normal and degenerate
      intervertebral disc, including stem/progenitor cells themselves and extracellular
      factors located within the stem cell niche, may provide effective insights into
      selecting the most suitable cell sources and improving or rebuilding the
      microenvironment favorable for endogenous or transplanted stem cells.

PMID- 21190534
TI  - Stem cell plasticity, neuroprotection and regeneration in human eye diseases.
AB  - Regeneration and plasticity refer to the ability of certain progenitor cells to
      produce cell lineages with specific morphological and functional settings. The
      pathway from a less delineated or immature phenotype to a mature or specialized
      one follows intricate routes where a monumental array of molecular elements,
      basically transcription factors and epigenetic regulators that turn off or on a
      specific phenotypic change, play a fundamental role. Nature itself offers
      procedures to healing strategies. Therapy approaches to pathologies in the realm
      of ophthalmology may benefit from the knowledge of the properties and mechanisms
      of activation of different routes controlling the pathways of cell definition and
      differentiation. Specification of cell identity, not only in terms of phenotypic
      traits, but also regarding the mechanisms of gene expression and epigenetic
      regulation, will provide new tools to manipulating cell fates and status, both
      forward and backwards. In the human eye, two main locations shelter stem cells:
      the limbus, which is situated in the limit of the cornea and the conjunctiva, and
      the ciliary body pars plana. Transplantation of limbal cells is currently used in
      certain pathologies where corneal epithelium is damaged. Therapeutic applications
      of retina progenitors are not yet fully developed due to the complexity of the
      cellular components of the multilayer retinal architecture. Animal models of
      Retinitis pigmentosa or Glaucoma offer an interesting approach to validate
      certain techniques, such as the direct injection of progenitors into the vitreal
      compartment, aimed to restoring retinal function.

PMID- 21190535
TI  - Effect of platelet lysate on the functional and molecular characteristics of
      mesenchymal stem cells isolated from adipose tissue.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) are non-hematopoietic, adult,
      fibroblast-like, multipotent cells that are plastic adherent in standard culture
      conditions. They can be isolated from several tissues, but it is always necessary
      to expand them for clinical practice. AIM: We investigated the effect of human
      platelet lysate (hPL) on the expansion of human MSCs isolated from adipose tissue
      (AT), comparing it with fetal bovine serum (FBS) and human platelet-poor plasma
      (hPPP). MATERIALS AND METHODS: Human AT-MSCs, hPL and hPPP were obtained from 7
      healthy subjects. AT-MSCs were seeded at 1500 cells/cm(2) and cultured in
      Dulbecco's modified Eagle's medium supplemented with 10% FBS, 10% hPPP or 10%
      hPL. Cells were harvested, counted and analyzed by flow cytometry every 7 days
      for 5 passages (P). The differentiation assays, RNA isolation and co-culture with
      allogeneic lymphocytes were performed at the end of P2. RESULTS: AT-MSCs achieved
      a better proliferation rate when cultured with hPL than with hPPP or FBS (20 +/-2
      versus 8 +/-3 and 6 +/-3, respectively, at the end of P5 [p<0.01]). hPL preserved
      the differentiation capacity and typical expression of surface antigens, avoiding
      the risks associated with the use of animal derivatives. AT-MSCs demonstrated a
      stronger inhibitory effect on lymphocyte proliferation with hPL than with other
      culture conditions, even at a AT-MSCs:T cells ratio of 1:10. The transcriptional
      level of matrix metalloproteinase 2, used to evaluate stemness, was very high in
      all conditions tested. CONCLUSIONS: hPL represents an effective and safe
      supplement for MSC expansion to be used in the clinical setting.

PMID- 21190536
TI  - The role of circulating endothelial progenitor cells in tumor angiogenesis.
AB  - There is great controversy over the origin and definition of murine endothelial
      progenitor cells (EPCs). EPCs are reportedly important for the repair and
      remodeling of the vasculature and are implicated in tumor angiogenesis. Many
      conflicting reports exist as to whether these EPCs arise from the bone marrow
      hematopoietic compartment or whether they are non-hematopoietic in origin, and
      these differences could be attributed to the wide variance in assays used to
      identify the cells and time points at which the data are collected. Recently,
      circulating murine EPCs have been characterized as CD45(-)CD13(+)CD117(+)FLK-1(+)
      expressing cells via flow cytometry and this phenotype varies from prior
      descriptions. This review will focus on the changing phenotypic definition of
      murine circulating EPCs and the evidence that has been published in support of
      the lineage of origin of circulating EPCs and the role EPCs play in tumor
      angiogenesis in the adult mouse.

PMID- 21190537
TI  - Current status and prospective application of stem cell-based therapies for
      spinal cord injury.
AB  - Spinal cord injuries (SCIs) are a common form of trauma that leaves a huge trail
      of morbidity and human suffering in its wake. They occur mostly among the young,
      causing severe physical, psychological, social and economic burdens. The
      treatment of this condition has rather been disappointing; most of the management
      strategies being mainly supportive and prophylactic. In recent years there has
      been an emerging interest in the use of stem cells to regenerate the nervous
      tissue that has been damaged or lost. Although there has been much hype and
      unfounded hope, modest successes have been witnessed, and it is possible that
      these therapeutic strategies may have much more to offer in the future. This
      paper will review the current strategies of exploring cell-based therapies,
      mainly different types of stem cells to treat SCI along with the evidence that
      has been accumulated over the past decade in a rational bench-to-bedside
      approach. Furthermore, critical aspects such as the mode of delivery and ethical
      considerations are also discussed along with feasible suggestions for future
      translational research to provide a contextual picture of the current state of
      advancements in this field. The impediments to regeneration in the site of injury
      are briefly explained along with the benefits and drawbacks of different cell
      types used in the treatment of this condition. We hope that this review will
      offer a significant insight into this challenging clinical condition.

PMID- 21190538
TI  - Mesenchymal stem cells neuronal differentiation ability: a real perspective for
      nervous system repair?
AB  - Mesenchymal Stem Cells (MSCs) are a bone marrow-derived population present in
      adult tissues that possess the important property of dividing when called upon
      and of differentiating into specialized cells. The evidence that MSCs were able
      to transdifferentiate into specialized cells of tissues different from bone
      marrow, in particular into nervous cells, opened up the possibility of using MSCs
      to substitute damaged neurons, that are normally not replaced but lost, in order
      to repair the Nervous System. The first neuronal differentiation protocols were
      based on the use of a mixture of toxic drugs which induced MSCs to rapidly
      acquire a neuronal-like morphology with the expression of specific neuronal
      markers. However, many subsequent studies demonstrated that the morphological and
      molecular modifications of MSCs were probably due to a stress response, rather
      than to a real differentiation into neuronal cells, thus throwing into question
      the possible use of MSCs to repair the nervous system. Currently, some papers are
      suggesting again that it may be possible to induce neuronal differentiation of
      MSCs by using several differentiation protocols, and by accompanying the
      morphological evidence of differentiation with functional evidence, thus
      demonstrating that MSC-derived cells not only seem to be neurons, but that they
      also function like neurons. In this review, we have attempted to shed light on
      the capacity of MSCs to genuinely differentiate into nervous cells, and to
      identify the most reliable protocols for obtaining neurons from MSCs for nervous
      system repair.

PMID- 21190539
TI  - Regulatory circuitries coordinated by transcription factors and microRNAs at the
      cornerstone of hematopoietic stem cell self-renewal and differentiation.
AB  - In mammals, hematopoiesis is the continuous formation of all blood cell types
      from a limited pool of hematopoietic stem cells (HSCs) residing in specialized
      niches in the bone marrow (BM). Hierarchical specification of hematopoietic
      lineages, as well as stem cell kinetics, are dynamic processes influenced by an
      intricate network of soluble growth factors and membrane-anchored signals
      orchestrated by the microenvironment (extrinsic signals), coupled with cell
      autonomous changes in gene expression (intrinsic signals). At the molecular
      level, during the early steps of hematopoietic differentiation from the HSC, the
      chromatin progressively becomes more accessible at genes poised for expression,
      rapidly followed by an increased expression of lineage-associated genes with
      concomitant repression of alternative-lineage genes, resulting in commitment and
      differentiation. These events are established by the coordinated action of
      transcription factors (TFs), chromatin remodeling factors and microRNAs (miRNAs).
      In this review we describe the combinatorial molecular circuitries managed by TFs
      and miRNAs underlying HSC emergence, maintenance, and lineage development.

PMID- 21190540
TI  - gamma-Secretase-regulated signaling pathways, such as notch signaling, mediate
      the differentiation of hematopoietic stem cells, development of the immune
      system, and peripheral immune responses.
AB  - Notch signaling mediates the fates of numerous cells in both invertebrates and
      vertebrates. In the immune system, Notch signalling contributes to the generation
      of hematopoietic stem cells (HSCs), the promotion of HSC self-renewal, T lineage
      commitment, intrathymic T cell development, and peripheral lymphocyte
      differentiation/activation. The intracellular domain (ICD) of Notch is released
      from the cell membrane by gamma-secretase and translocates to the nucleus to
      modulate gene expression. Hence, gamma-secretase plays a central role in the
      regulation of Notch signaling. More than five dozen type 1 transmembrane
      proteins, including amyloid precursor protein, Notch, and Delta, are substrates
      for gamma-secretase and their ICDs are released from the cell membrane.
      Therefore, it is highly possible that mechanisms similar to Notch signaling may
      widely contribute to gamma-secretase-regulated signaling. Besides Notch, some
      transmembrane proteins such as CD44 and CSF-1R, which are important for immune
      responses, have been reported as substrates for gamma-secretase. Since the ICDs
      of these proteins are also released by gamma-secretase from the cell membrane and
      localize to the nucleus, it is thought that these ICDs modulate gene expression.
      Thus, gamma-secretase-regulated signaling, including Notch signaling, may play a
      wide range of roles in the immune system.

PMID- 21190541
TI  - The activity of matrix metalloproteinase-9 is part of the mechanism of cell-to
      cell HIV-1 endocytosis in dendritic cells.
AB  - Human immunodeficiency virus (HIV) starts to replicate upon virus-cell fusion
      mediated by the CD4-Env-coreceptor interaction. HIV enters target cells also
      through endocytosis, a mechanism which rarely leads to HIV replication. Both
      modes of entry are greatly improved by cell-cell contact. We recently reported
      that the contact of human primary dendritic cells with HIV-1 infected cells leads
      to high levels of virus endocytosis and HIV-1 antigen presentation activity in
      dendritic cells. Here, we provide evidence that the activity of matrix
      metalloproteinase (MMP)-9 is involved in the mechanism of cell-to-cell HIV-1
      endocytosis in DCs. Accordingly, the specific inhibition of MMP-9 led to reduced
      extents of HIV-1 antigen presentation activity. The identification of cell
      molecules involved in the cell-to-cell HIV-1 endocytosis would be of significance
      for better understanding the mechanisms underlying the induction of the anti-HIV
      adaptive immune response.

PMID- 21190542
TI  - Recent progress in patterned silicon nanowire arrays: fabrication, properties and
      applications.
AB  - Currently there is great interest in patterned silicon nanowire arrays and
      applications. The accurately controlled fabrication of patterned silicon nanowire
      arrays with the desirable axial crystallographic orientation using simpler and
      quicker ways is very desirable and of great importance to material synthesis and
      future nanoscale optoelectronic devices that employ silicon. The recent advances
      in manipulating patterned silicon nanowire arrays and patents are reviewed with a
      focus on the progress of nanowire fabrication and applications.

PMID- 21190543
TI  - Synthetic LXR agonist suppresses endogenous cholesterol biosynthesis and
      efficiently lowers plasma cholesterol.
AB  - The liver X receptors (LXRs) are key regulators of genes involved in cholesterol
      homeostasis. Natural ligands and activators of LXRs are oxysterols. Numerous
      steroidal and non-steroidal synthetic LXR ligands are under development as
      potential drugs for individuals suffering from lipid disorders. N,N-dimethyl
      3beta-hydroxycholenamide (DMHCA) is a steroidal ligand of LXRs that exerts anti
      atherogenic effects in apolipoprotein E-deficient mice without causing negative
      side effects such as liver steatosis or hypertriglyceridemia. In this report, we
      investigated the consequences of DMHCA treatment on cholesterol homeostasis in
      vivo and in vitro. Despite its hydrophobicity, DMHCA is readily absorbed by
      C57BL/6 mice and taken up by intestinal cells, the lung, heart and kidneys, but
      is undetectable in the brain. DMHCA significantly reduces cholesterol absorption
      and uptake in duodenum and jejunum of the small intestine and in turn leads to a
      reduction of plasma cholesterol by 24%. The most striking finding of this study
      is that DMHCA inhibited the enzyme 3beta-hydroxysterol-Delta24-reductase
      resulting in an accumulation of desmosterol in the plasma and in feces. Thus, the
      reduction of plasma cholesterol was due to a block in the final step of
      cholesterol biosynthesis. Taken together, DMHCA is an interesting compound with
      properties distinct from other LXR ligands and might be used to study desmosterol
      mediated effects in cells and tissues.

PMID- 21190545
TI  - Caught you: threats to confidentiality due to the public release of large-scale
      genetic data sets.
AB  - BACKGROUND: Large-scale genetic data sets are frequently shared with other
      research groups and even released on the Internet to allow for secondary
      analysis. Study participants are usually not informed about such data sharing
      because data sets are assumed to be anonymous after stripping off personal
      identifiers. DISCUSSION: The assumption of anonymity of genetic data sets,
      however, is tenuous because genetic data are intrinsically self-identifying. Two
      types of re-identification are possible: the "Netflix" type and the "profiling"
      type. The "Netflix" type needs another small genetic data set, usually with less
      than 100 SNPs but including a personal identifier. This second data set might
      originate from another clinical examination, a study of leftover samples or
      forensic testing. When merged to the primary, unidentified set it will re
      identify all samples of that individual. Even with no second data set at hand, a
      "profiling" strategy can be developed to extract as much information as possible
      from a sample collection. Starting with the identification of ethnic subgroups
      along with predictions of body characteristics and diseases, the asthma kids case
      as a real-life example is used to illustrate that approach. SUMMARY: Depending on
      the degree of supplemental information, there is a good chance that at least a
      few individuals can be identified from an anonymized data set. Any re
      identification, however, may potentially harm study participants because it will
      release individual genetic disease risks to the public.

PMID- 21190544
TI  - Targeted protein depletion in Saccharomyces cerevisiae by activation of a
      bidirectional degron.
AB  - BACKGROUND: Tools for in vivo manipulation of protein abundance or activity are
      highly beneficial for life science research. Protein stability can be efficiently
      controlled by conditional degrons, which induce target protein degradation at
      restrictive conditions. RESULTS: We used the yeast Saccharomyces cerevisiae for
      development of a conditional, bidirectional degron to control protein stability,
      which can be fused to the target protein N-terminally, C-terminally or placed
      internally. Activation of the degron is achieved by cleavage with the tobacco
      etch virus (TEV) protease, resulting in quick proteolysis of the target protein.
      We found similar degradation rates of soluble substrates using destabilization by
      the N- or C-degron. C-terminal tagging of essential yeast proteins with the
      bidirectional degron resulted in deletion-like phenotypes at non-permissive
      conditions. Developmental process-specific mutants were created by N- or C
      terminal tagging of essential proteins with the bidirectional degron in
      combination with sporulation-specific production of the TEV protease.
      CONCLUSIONS: We developed a system to influence protein abundance and activity
      genetically, which can be used to create conditional mutants, to regulate the
      fate of single protein domains or to design artificial regulatory circuits. Thus,
      this method enhances the toolbox to manipulate proteins in systems biology
      approaches considerably.

PMID- 21190546
TI  - Referrals to a regional allergy clinic - an eleven year audit.
AB  - BACKGROUND: Allergy is a serious and apparently increasing public health problem
      yet relatively little is known about the types of allergy seen in routine
      tertiary practice, including their spatial distribution, co-occurrence or
      referral patterns. This study reviewed referrals over an eleven year period to a
      regional allergy clinic that had a well defined geographical boundary. For those
      patients confirmed as having an allergy we explored: (i) differences over time
      and by demographics, (ii) types of allergy, (iii) co-occurrence, and (iv) spatial
      distributions. METHODS: Data were extracted from consultant letters to GPs, from
      September 1998 to September 2009, for patients confirmed as having an allergy.
      Other data included referral statistics and population data by postcode. Simple
      descriptive analysis was used to describe types of allergy. We calculated 11 year
      standardised morbidity ratios for postcode districts and checked for spatial
      clustering. We present maps showing 11 year rates by postcode, and 'difference'
      maps which try to separate referral effect from possible environmental effect.
      RESULTS: Of 5778 referrals, 961 patients were diagnosed with an allergy. These
      were referred by a total of 672 different GPs. There were marked differences in
      referral patterns between GP practices and also individual GPs. The mean age of
      patients was 35 and there were considerably more females (65%) than males.
      Airborne allergies were the most frequent (623), and there were very high rates
      of co-occurrence of pollen, house dust mite, and animal hair allergies. Less than
      half (410) patients had a food allergy, with nuts, fruit, and seafood being the
      most common allergens. Fifteen percent (142) had both a food and a non-food
      allergy. Certain food allergies were more likely to co-occur, for example,
      patients allergic to dairy products were more likely to be allergic to egg.There
      were age differences by types of allergy; people referred with food allergies
      were on average 5 years younger than those with other allergies, and those
      allergic to nuts were much younger (26 Vs 38) than those with other food
      allergies.There was clear evidence for spatial clustering with marked clustering
      around the referral hospital. However, the geographical distribution varied
      between allergies; airborne (particularly pollen allergies) clustered in North
      Dartmoor and Exmoor, food allergies (particularly nut allergies) in the South
      Hams, and on small numbers, some indication of seafood allergy in the far south
      west of Cornwall and in the Padstow area. CONCLUSIONS: This study shows marked
      geographical differences in allergy referrals which are likely to reflect a
      combination of environmental factors and GP referral patterns. The data suggest
      that GPs may benefit from education and ongoing decision support and be supported
      by public education on the nature of allergy. It suggests further research into
      what happens to patients with allergy where there has been low use of tertiary
      services and further research into cross-reactivity and co-occurrence, and
      spatial distribution of allergy.

PMID- 21190547
TI  - Normalization using ploidy and genomic DNA copy number allows absolute
      quantification of transcripts, proteins and metabolites in cells.
AB  - BACKGROUND: Quantification of transcripts, proteins, or metabolites is
      straightforward when the factor used to normalize these values remains constant
      between samples. However, normalization factors often vary among samples and thus
      must be developed for each new analytical method. RESULTS: We demonstrate
      quantification of transcript and protein levels in Arabidopsis based on genomic
      DNA copy number. We extracted total nucleic acid from 3-week-old rosette leaves
      of wild-type Arabidopsis and the pale-green/dwarf mutant, abc4, and quantified
      the number of transcripts by quantitative reverse-transcription PCR using genomic
      DNA copy number and ploidy (as determined by cytometry) for normalization. Our
      data indicated that normalization using genes commonly employed as references
      resulted in inaccuracies in transcript levels of the genes RBC-L and RBC-S
      (encoding the large and small subunits, respectively, of ribulose 1,5
      bisphosphate carboxylase/oxygenase) in wild type and mutant. Normalization using
      genomic DNA copy number and ploidy, however, appropriately showed that the RBC-L
      and RBC-S transcript levels per cell in the mutant were significantly lower than
      that in wild type. Furthermore, quantification revealed that a cell of a 3-week
      old wild-type Arabidopsis rosette leaf had an average of 7.5 * 103 transcripts of
      RBC-L, 9.9 * 103 transcripts of RBC-S, and 1.4 * 106 18S rRNA. We similarly
      analyzed the accumulation of RBC-L and LHCP (light-harvesting chlorophyll a/b
      protein) in wild type and mutant based on ploidy and genomic DNA copy number that
      was determined by direct quantitative PCR analysis of extracts using a DNA
      polymerase tolerant to a wide range of common PCR inhibitors. Furthermore, we
      estimated the number of RBC-L molecules (2.63 * 108) and chlorophyll molecules
      (1.85 * 109) in each cell in 3-week-old wild-type rosette leaves; these values
      had relatively low coefficients of variation, underscoring the reliability of our
      method. CONCLUSION: Genomic DNA copy number and ploidy are useful as general
      normalization factors, providing an easy method for determining the number of
      transcripts, proteins, and metabolites in a cell.

PMID- 21190548
TI  - Statin pretreatment diminishes the levels of myocardial ischemia markers not only
      in CABG.

PMID- 21190549
TI  - Six3 demarcates the anterior-most developing brain region in bilaterian animals.
AB  - BACKGROUND: The heads of annelids (earthworms, polychaetes, and others) and
      arthropods (insects, myriapods, spiders, and others) and the arthropod-related
      onychophorans (velvet worms) show similar brain architecture and for this reason
      have long been considered homologous. However, this view is challenged by the
      'new phylogeny' placing arthropods and annelids into distinct superphyla,
      Ecdysozoa and Lophotrochozoa, together with many other phyla lacking elaborate
      heads or brains. To compare the organisation of annelid and arthropod heads and
      brains at the molecular level, we investigated head regionalisation genes in
      various groups. Regionalisation genes subdivide developing animals into molecular
      regions and can be used to align head regions between remote animal phyla.
      RESULTS: We find that in the marine annelid Platynereis dumerilii, expression of
      the homeobox gene six3 defines the apical region of the larval body, peripherally
      overlapping the equatorial otx+ expression. The six3+ and otx+ regions thus
      define the developing head in anterior-to-posterior sequence. In another annelid,
      the earthworm Pristina, as well as in the onychophoran Euperipatoides, the
      centipede Strigamia and the insects Tribolium and Drosophila, a six3/optix+
      region likewise demarcates the tip of the developing animal, followed by a more
      posterior otx/otd+ region. Identification of six3+ head neuroectoderm in
      Drosophila reveals that this region gives rise to median neurosecretory brain
      parts, as is also the case in annelids. In insects, onychophorans and
      Platynereis, the otx+ region instead harbours the eye anlagen, which thus occupy
      a more posterior position. CONCLUSIONS: These observations indicate that the
      annelid, onychophoran and arthropod head develops from a conserved anterior
      posterior sequence of six3+ and otx+ regions. The six3+ anterior pole of the
      arthropod head and brain accordingly lies in an anterior-median embryonic region
      and, in consequence, the optic lobes do not represent the tip of the neuraxis.
      These results support the hypothesis that the last common ancestor of annelids
      and arthropods already possessed neurosecretory centres in the most anterior
      region of the brain. In light of its broad evolutionary conservation in
      protostomes and, as previously shown, in deuterostomes, the six3-otx head
      patterning system may be universal to bilaterian animals.

PMID- 21190550
TI  - Nasal carriage and antimicrobial susceptibility of Staphylococcus aureus in
      healthy preschool children in Ujjain, India.
AB  - BACKGROUND: There is increasing evidence that community acquired S. aureus
      infections are spreading among healthy children. Nasal colonization with S.
      aureus plays pivotal role in the increasing prevalence of resistant community
      acquired S. aureus infections worldwide. A regular surveillance system is
      important in ensuring quality of patient care. The aim of the study was to assess
      the prevalence of and the factors associated with nasal carriage of S. aureus and
      its antibiotic sensitivity pattern among healthy children in Ujjain, India.
      METHODS: A prospective study was done in paediatric outpatient clinics of R.D.
      Gardi medical college Ujjain, India. Healthy children from 1 month to 59 months
      of age were included. Information on previously known risk factors for nasal
      colonization was collected using a pre-tested questionnaire. Swabs from anterior
      nares were collected and transported in Amies transport media with charcoal and
      cultured on 5% sheep blood agar. Antibiotic sensitivity tests were performed
      using Kirby Bauer's disc diffusion method according to performance standards of
      Clinical and Laboratory Standard Institute guidelines. RESULTS: Of the 1,562
      children from 1-month up-to five years of age included in the study 98 children
      tested positive for nasal carriage of S. aureus. The prevalence of nasal carriage
      of S. aureus was 6.3% (95% CI 5.1-7.5) out of which 16.3% (95% CI 8.9-23.8) were
      methicillin-resistant S. aureus (MRSA). The factors associated with nasal
      carriage were "child attending preschool" (OR 4.26, 95% CI 2.25-8.03; P = 0.007)
      or "school" (OR 3.02, 95% CI 1.27-7.18; P < 0.001) and "family size more than 10
      members" (OR 2.76 95% CI 1.06-7.15; P = 0.03). The sensitivity pattern of
      isolated S. aureus showed resistance to commonly used oral antibiotics while
      resistance to glycopeptides was not noted. CONCLUSIONS: We found a relatively low
      rate of nasal carriage of S. aureus in children below five years when compared to
      children of older age groups in India. Yet, prevalence of MRSA was relatively
      high.

PMID- 21190551
TI  - Common promoter variants of the NDUFV2 gene do not confer susceptibility to
      schizophrenia in Han Chinese.
AB  - BACKGROUND: The NADH-ubiquinone oxidoreductase flavoprotein gene (NDUFV2), which
      encodes a 24 kD mitochondrial complex I subunit, has been reported to be
      positively associated with schizophrenia and bipolar disorder in different
      populations. METHODS: We genotyped the promoter variants of this gene (rs6506640
      and rs1156044) by direct sequencing in 529 unrelated Han Chinese schizophrenia
      patients and 505 matched controls. Fisher's Exact test was performed to assess
      whether these two reported single nucleotide polymorphisms (SNPs) confer
      susceptibility to schizophrenia in Chinese. RESULTS: Allele, genotype and
      haplotype comparison between the case and control groups showed no statistical
      significance, suggesting no association between the NDUFV2 gene promoter variants
      and schizophrenia in Han Chinese. CONCLUSION: The role of NDUFV2 played in
      schizophrenia needs to be further studied. Different racial background and/or
      population substructure might account for the inconsistent results between
      studies.

PMID- 21190552
TI  - Amyloid precursor protein selective gamma-secretase inhibitors for treatment of
      Alzheimer's disease.
AB  - INTRODUCTION: Inhibition of gamma-secretase presents a direct target for lowering
      Abeta production in the brain as a therapy for Alzheimer's disease (AD). However,
      gamma-secretase is known to process multiple substrates in addition to amyloid
      precursor protein (APP), most notably Notch, which has limited clinical
      development of inhibitors targeting this enzyme. It has been postulated that APP
      substrate selective inhibitors of gamma-secretase would be preferable to non
      selective inhibitors from a safety perspective for AD therapy. METHODS: In vitro
      assays monitoring inhibitor potencies at APP gamma-site cleavage (equivalent to
      Abeta40), and Notch epsilon-site cleavage, in conjunction with a single cell
      assay to simultaneously monitor selectivity for inhibition of Abeta production
      vs. Notch signaling were developed to discover APP selective gamma-secretase
      inhibitors. In vivo efficacy for acute reduction of brain Abeta was determined in
      the PDAPP transgene model of AD, as well as in wild-type FVB strain mice. In vivo
      selectivity was determined following seven days x twice per day (b.i.d.)
      treatment with 15 mg/kg/dose to 1,000 mg/kg/dose ELN475516, and monitoring brain
      Abeta reduction vs. Notch signaling endpoints in periphery. RESULTS: The APP
      selective gamma-secretase inhibitors ELN318463 and ELN475516 reported here behave
      as classic gamma-secretase inhibitors, demonstrate 75- to 120-fold selectivity
      for inhibiting Abeta production compared with Notch signaling in cells, and
      displace an active site directed inhibitor at very high concentrations only in
      the presence of substrate. ELN318463 demonstrated discordant efficacy for
      reduction of brain Abeta in the PDAPP compared with wild-type FVB, not observed
      with ELN475516. Improved in vivo safety of ELN475516 was demonstrated in the 7d
      repeat dose study in wild-type mice, where a 33% reduction of brain Abeta was
      observed in mice terminated three hours post last dose at the lowest dose of
      inhibitor tested. No overt in-life or post-mortem indications of systemic
      toxicity, nor RNA and histological end-points indicative of toxicity attributable
      to inhibition of Notch signaling were observed at any dose tested. CONCLUSIONS:
      The discordant in vivo activity of ELN318463 suggests that the potency of gamma
      secretase inhibitors in AD transgenic mice should be corroborated in wild-type
      mice. The discovery of ELN475516 demonstrates that it is possible to develop APP
      selective gamma-secretase inhibitors with potential for treatment for AD.

PMID- 21190553
TI  - Regulation of polar peptidoglycan biosynthesis by Wag31 phosphorylation in
      mycobacteria.
AB  - BACKGROUND: Sensing and responding to environmental changes is a central aspect
      of cell division regulation. Mycobacterium tuberculosis contains eleven Ser/Thr
      kinases, two of which, PknA and PknB, are key signaling molecules that regulate
      cell division/morphology. One substrate of these kinases is Wag31, and we
      previously showed that partial depletion of Wag31 caused morphological changes
      indicative of cell wall defects, and that the phosphorylation state of Wag31
      affected cell growth in mycobacteria. In the present study, we further
      characterized the role of the Wag31 phosphorylation in polar peptidoglycan
      biosynthesis. RESULTS: We demonstrate that the differential growth among cells
      expressing different wag31 alleles (wild-type, phosphoablative, or
      phosphomimetic) is caused by, at least in part, dissimilar nascent peptidoglycan
      biosynthesis. The phosphorylation state of Wag31 is found to be important for
      protein-protein interactions between the Wag31 molecules, and thus, for its polar
      localization. Consistent with these results, cells expressing a phosphomimetic
      wag31 allele have a higher enzymatic activity in the peptidoglycan biosynthetic
      pathway. CONCLUSIONS: The Wag31Mtb phosphorylation is a novel molecular mechanism
      by which Wag31Mtb regulates peptidoglycan synthesis and thus, optimal growth in
      mycobacteria.

PMID- 21190554
TI  - Bone marrow lesions predict site-specific cartilage defect development and volume
      loss: a prospective study in older adults.
AB  - INTRODUCTION: Recent evidence suggests that bone marrow lesions (BMLs) play a
      pivotal role in knee osteoarthritis (OA). The aims of this study were to
      determine: 1) whether baseline BML presence and/or severity predict site-specific
      cartilage defect progression and cartilage volume loss; and 2) whether baseline
      cartilage defects predict site-specific BML progression. METHODS: A total of 405
      subjects (mean age 63 years, range 52 to 79) were measured at baseline and
      approximately 2.7 years later. Magnetic resonance imaging (MRI) of the right knee
      was performed to measure knee cartilage volume, cartilage defects (0 to 4), and
      BMLs (0 to 3) at the medial tibial (MT), medial femoral (MF), lateral tibial
      (LT), and lateral femoral (LF) sites. Logistic regression and generalized
      estimating equations were used to examine the relationship between BMLs and
      cartilage defects and cartilage volume loss. RESULTS: At all four sites, baseline
      BML presence predicted defect progression (odds ratio (OR) 2.4 to 6.4, all P <
      0.05), and cartilage volume loss (-0.9 to -2.9% difference per annum, all P <
      0.05) at the same site. In multivariable analysis, there was a significant
      relationship between BML severity and defect progression at all four sites (OR
      1.8 to 3.2, all P < 0.05) and BML severity and cartilage volume loss at the MF,
      LT, and LF sites (beta -22.1 to -42.0, all P < 0.05). Additionally, baseline
      defect severity predicted BML progression at the MT and LF sites (OR 3.3 to 3.7,
      all P < 0.01). Lastly, there was a greater increase in cartilage volume loss at
      the MT and LT sites when both larger defects and BMLs were present at baseline
      (all P < 0.05). CONCLUSIONS: Baseline BMLs predicted site-specific defect
      progression and cartilage volume loss in a dose-response manner suggesting BMLs
      may have a local effect on cartilage homeostasis. Baseline defects predicted site
      specific BML progression, which may represent increased bone loading adjacent to
      defects. These results suggest BMLs and defects are interconnected and play key
      roles in knee cartilage volume loss; thus, both should be considered targets for
      intervention.

PMID- 21190555
TI  - Natural history and clinical significance of MRI-detected bone marrow lesions at
      the knee: a prospective study in community dwelling older adults.
AB  - INTRODUCTION: There are conflicting data on the natural history and clinical
      significance of bone marrow lesions (BMLs). The aims of this study were to
      describe the natural history of MRI-detected BMLs at the knee using a
      quantitative measure and examine the association of BMLs with pain, function and
      stiffness scores, and total knee replacement (TKR) surgery. METHODS: A total of
      395 older males and females were randomly selected from the general population
      (mean age 63 years, range 52 to 79) and measured at baseline and approximately
      2.7 years later. BMLs were determined using T2-weighted fat saturation MRI by
      measuring the maximum area of the lesion. Reproducibility was excellent
      (intraclass correlation coefficient (ICC): 0.97). Pain, function, and stiffness
      were assessed by Western Ontario and McMaster Universities Osteoarthritis (WOMAC)
      scores. X-ray was used to assess radiographic osteoarthritis (ROA) at baseline.
      RESULTS: At baseline, 43% (n = 168/395) had a BML. Of these 25% decreased in size
      and 24% increased. Of the remaining sample (n = 227), 7% developed a new BML. In
      a multivariable model, a change in BML size was associated with a change in pain
      and function scores (beta = 1.13 to 2.55 per 1 SD increase, all P < 0.05), only
      in those participants without ROA. Lastly, baseline BML severity predicted TKR
      surgery (odds ratio (OR) 2.10/unit, P = 0.019). CONCLUSIONS: In a population
      based sample, BMLs (assessed by measuring maximal area) were not static, with
      similar proportions both worsening and improving. A change in BML size was
      associated with changes in pain in those without established ROA. This finding
      suggests that fluctuating knee pain may be attributable to BMLs in those
      participants with early stage disease. Baseline BMLs also predicted TKR surgery.
      These findings suggest therapeutic interventions aimed at altering the natural
      history of BMLs should be considered.

PMID- 21190556
TI  - The association of aggressive and chronic periodontitis with systemic
      manifestations and dental anomalies in a jordanian population: a case control
      study.
AB  - BACKGROUND: The relationship between dental anomalies and periodontitis has not
      been documented by earlier studies. Although psychological factors have been
      implicated in the etiopathogenesis of periodontitis, very little information has
      so far been published about the association of anxiety and depression with
      aggressive periodontitis. The aim of this study was to investigate the
      association of chronic periodontitis and aggressive periodontitis with certain
      systemic manifestations and dental anomalies. METHODS: A total of 262 patients
      (100 chronic periodontitis, 81 aggressive periodontitis and 81 controls),
      attending the Periodontology clinics at Jordan University of Science and
      Technology, Dental Teaching Centre) were included. All subjects had a full
      periodontal and radiographic examination to assess the periodontal condition and
      to check for the presence of any of the following dental anomalies: dens
      invaginatus, dens evaginatus, congenitally missing lateral incisors or peg-shaped
      lateral incisors. Participants were interrogated regarding the following:
      depressive mood, fatigue, weight loss, or loss of appetite; and their anxiety and
      depression status was assessed using the Hospital Anxiety and Depression (HAD)
      scale. RESULTS: Patients with aggressive periodontitis reported more systemic
      symptoms (51%) than the chronic periodontitis (36%) and control (30%) patients (p
      < 0.05). Aggressive periodontitis patients had a higher tendency for both anxiety
      and depression than chronic periodontitis and control patients. Dental anomalies
      were significantly (p < 0.05) more frequent among both of chronic and aggressive
      periodontitis patients (15% and 16%, respectively), compared to controls.
      CONCLUSION: In this group of Jordanians, systemic symptoms were strongly
      associated with aggressive periodontitis, and dental anomalies were positively
      associated with both aggressive and chronic periodontitis.

PMID- 21190557
TI  - Early decrements in bone density after completion of neoadjuvant chemotherapy in
      pediatric bone sarcoma patients.
AB  - BACKGROUND: Bone mineral density (BMD) accrual during childhood and adolescence
      is important for attaining peak bone mass. BMD decrements have been reported in
      survivors of childhood bone sarcomas. However, little is known about the onset
      and development of bone loss during cancer treatment. The objective of this cross
      sectional study was to evaluate BMD in newly diagnosed Ewing's and osteosarcoma
      patients by means of dual-energy x-ray absorptiometry (DXA) after completion of
      neoadjuvant chemotherapy. METHODS: DXA measurements of the lumbar spine (L2-4),
      both femora and calcanei were performed perioperatively in 46 children and
      adolescents (mean age: 14.3 years, range: 8.6-21.5 years). Mean Z-scores, areal
      BMD (g/cm2), calculated volumetric BMD (g/cm3) and bone mineral content (BMC, g)
      were determined. RESULTS: Lumbar spine mean Z-score was -0.14 (95% CI: -0.46 to
      0.18), areal BMD was 1.016 g/cm2 (95% CI: 0.950 to 1.082) and volumetric BMD was
      0.330 g/cm3 (95% CI: 0.314 to 0.347) which is comparable to healthy peers. For
      patients with a lower extremity tumor (n = 36), the difference between the
      affected and non-affected femoral neck was 12.1% (95% CI: -16.3 to -7.9) in areal
      BMD. The reduction of BMD was more pronounced in the calcaneus with a difference
      between the affected and contralateral side of 21.7% (95% CI: -29.3 to -14.0) for
      areal BMD. Furthermore, significant correlations for femoral and calcaneal DXA
      measurements were found with Spearman-rho coefficients ranging from rho = 0.55 to
      rho = 0.80. CONCLUSIONS: The tumor disease located in the lower extremity in
      combination with offloading recommendations induced diminished BMD values,
      indicating local osteopenia conditions. However, the results revealed no
      significant decrements of lumbar spine BMD in pediatric sarcoma patients after
      completion of neoadjuvant chemotherapy. Nevertheless, it has to be taken into
      account that bone tumor patients may experience BMD decrements or secondary
      osteoporosis in later life. Furthermore, the peripheral assessment of BMD in the
      calcaneus via DXA is a feasible approach to quantify bone loss in the lower
      extremity in bone sarcoma patients and may serve as an alternative procedure,
      when the established assessment of femoral BMD is not practicable due to
      endoprosthetic replacements.

PMID- 21190558
TI  - A single hydrophobic cleft in the Escherichia coli processivity clamp is
      sufficient to support cell viability and DNA damage-induced mutagenesis in vivo.
AB  - BACKGROUND: The ubiquitous family of DnaN sliding processivity clamp proteins
      plays essential roles in DNA replication, DNA repair, and cell cycle progression,
      in part by managing the actions of the different proteins involved in these
      processes. Interactions of the homodimeric Escherichia coli beta clamp with its
      known partners involves multiple surfaces, including a hydrophobic cleft located
      near the C-terminus of each clamp protomer. RESULTS: A mutant E. coli beta clamp
      protein lacking a functional hydrophobic cleft (betaC) complemented the
      temperature sensitive growth phenotype of a strain bearing the dnaN159 allele,
      which encodes a thermolabile mutant clamp protein (beta159). Complementation was
      conferred by a betaC/beta159 heterodimer, and was observed only in the absence of
      the dinB gene, which encodes DNA polymerase IV (Pol IV). Furthermore, the
      complemented strain was proficient for umuDC (Pol V)--dependent ultraviolet light
      (UV)--induced mutagenesis. CONCLUSIONS: Our results suggest that a single cleft
      in the homodimeric E. coli beta sliding clamp protein is sufficient to support
      both cell viability, as well as Pol III, Pol IV, and Pol V function in vivo.
      These findings provide further support for a model in which different Pols switch
      places with each other on DNA using a single cleft in the clamp.

PMID- 21190559
TI  - Sperry versus Hebb: topographic mapping in Isl2/EphA3 mutant mice.
AB  - BACKGROUND: In wild-type mice, axons of retinal ganglion cells establish
      topographically precise projection to the superior colliculus of the midbrain.
      This means that axons of neighboring retinal ganglion cells project to the
      proximal locations in the target. The precision of topographic projection is a
      result of combined effects of molecular labels, such as Eph receptors and
      ephrins, and correlated neural activity. In the Isl2/EphA3 mutant mice the
      expression levels of molecular labels are changed. As a result the topographic
      projection is rewired so that the neighborhood relationships between retinal cell
      axons are disrupted. RESULTS: Here we study the computational model for
      retinocollicular connectivity formation that combines the effects of molecular
      labels and correlated neural activity. We argue that the effects of correlated
      activity presenting themselves in the form of Hebbian learning rules can
      facilitate the restoration of the topographic connectivity even when the
      molecular labels carry conflicting instructions. This occurs because the
      correlations in electric activity carry information about retinal cells' origin
      that is independent on molecular labels. We argue therefore that partial
      restoration of the topographic property of the retinocollicular projection
      observed in Isl2/EphA3 heterozygous knockin mice may be explained by the effects
      of correlated neural activity. We address the maps observed in Isl2/EphA3
      knockin/EphA4 knockout mice in which the levels of retinal labels are uniformly
      reduced. These maps can be explained by either the saturation of EphA receptor
      mapping leading to the relative signaling model or by the reverse signaling
      conveyed by ephrin-As expressed by retinal axons. CONCLUSION: According to our
      model, experiments in Isl2/EphA3 knock-in mice test the interactions between
      effects of molecular labels and correlated activity during the development of
      neural connectivity. Correlated activity can partially restore topographic order
      even when molecular labels carry conflicting information.

PMID- 21190560
TI  - Respiratory support withdrawal in intensive care units: families, physicians and
      nurses views on two hypothetical clinical scenarios.
AB  - INTRODUCTION: Evidence suggests that dying patients' physical and emotional
      suffering is inadequately treated in intensive care units. Although there are
      recommendations regarding decisions to forgo life-sustaining therapy, deciding on
      withdrawal of life support is difficult, and it is also difficult to decide who
      should participate in this decision. METHODS: We distributed a self-administered
      questionnaire in 13 adult intensive care units (ICUs) assessing the attitudes of
      physicians and nurses regarding end-of-life decisions. Family members from a
      medical-surgical ICU in a tertiary cancer hospital were also invited to
      participate. Questions were related to two hypothetical clinical scenarios, one
      with a competent patient and the other with an incompetent patient, asking
      whether the ventilator treatment should be withdrawn and about who should make
      this decision. RESULTS: Physicians (155) and nurses (204) of 12 ICUs agreed to
      take part in this study, along with 300 family members. The vast majority of
      families (78.6%), physicians (74.8%) and nurses (75%) want to discuss end-of-life
      decisions with competent patients. Most of the physicians and nurses desire
      family involvement in end-of-life decisions. Physicians are more likely to
      propose withdrawal of the ventilator with competent patients than with
      incompetent patients (74.8% * 60.7%, P = 0.028). When the patient was
      incompetent, physicians (34.8%) were significantly less prone than nurses (23.0%)
      and families (14.7%) to propose decisions regarding withdrawal of the ventilator
      support (P < 0.001). CONCLUSIONS: Physicians, nurses and families recommended
      limiting life-support therapy with terminally ill patients and favored family
      participation. In decisions concerning an incompetent patient, physicians were
      more likely to maintain the therapy.

PMID- 21190562
TI  - PC3 prostate tumor-initiating cells with molecular profile
      FAM65Bhigh/MFI2low/LEF1low increase tumor angiogenesis.
AB  - BACKGROUND: Cancer stem-like cells are proposed to sustain solid tumors by virtue
      of their capacity for self-renewal and differentiation to cells that comprise the
      bulk of the tumor, and have been identified for a variety of cancers based on
      characteristic clonal morphologies and patterns of marker gene expression.
      METHODS: Single cell cloning and spheroid culture studies were used to identify a
      population of cancer stem-like cells in the androgen-independent human prostate
      cancer cell line PC3. RESULTS: We demonstrate that, under standard culture
      conditions, ~10% of PC3 cells form holoclones with cancer stem cell
      characteristics. These holoclones display high self-renewal capability in
      spheroid formation assays under low attachment and serum-free culture conditions,
      retain their holoclone morphology when passaged at high cell density, exhibit
      moderate drug resistance, and show high tumorigenicity in scid immunodeficient
      mice. PC3 holoclones readily form spheres, and PC3-derived spheres yield a high
      percentage of holoclones, further supporting their cancer stem cell-like nature.
      We identified one gene, FAM65B, whose expression is consistently up regulated in
      PC3 holoclones compared to paraclones, the major cell morphology in the parental
      PC3 cell population, and two genes, MFI2 and LEF1, that are consistently down
      regulated. This molecular profile, FAM65Bhigh/MFI2low/LEF1low, also characterizes
      spheres generated from parental PC3 cells. The PC3 holoclones did not show
      significant enriched expression of the putative prostate cancer stem cell markers
      CD44 and integrin alpha2beta1. PC3 tumors seeded with holoclones showed dramatic
      down regulation of FAM65B and dramatic up regulation of MFI2 and LEF1, and
      unexpectedly, a marked increase in tumor vascularity compared to parental PC3
      tumors, suggesting a role of cancer stem cells in tumor angiogenesis.
      CONCLUSIONS: These findings support the proposal that PC3 tumors are sustained by
      a small number of tumor-initiating cells with stem-like characteristics,
      including strong self-renewal and pro-angiogenic capability and marked by the
      expression pattern FAM65Bhigh/MFI2low/LEF1low. These markers may serve as targets
      for therapies designed to eliminate cancer stem cell populations associated with
      aggressive, androgen-independent prostate tumors such as PC3.

PMID- 21190561
TI  - Evolution of gene regulation of pluripotency--the case for wiki tracks at genome
      browsers.
AB  - BACKGROUND: Experimentally validated data on gene regulation are hard to obtain.
      In particular, information about transcription factor binding sites in regulatory
      regions are scattered around in the literature. This impedes their systematic in
      context analysis, e.g. the inference of their conservation in evolutionary
      history. RESULTS: We demonstrate the power of integrative bioinformatics by
      including curated transcription factor binding site information into the UCSC
      genome browser, using wiki and custom tracks, which enable easy publication of
      annotation data. Data integration allows to investigate the evolution of gene
      regulation of the pluripotency-associated genes Oct4, Sox2 and Nanog. For the
      first time, experimentally validated transcription factor binding sites in the
      regulatory regions of all three genes were assembled together based on manual
      curation of data from 39 publications. Using the UCSC genome browser, these data
      were then visualized in the context of multi-species conservation based on
      genomic alignment. We confirm previous hypotheses regarding the evolutionary age
      of specific regulatory patterns, establishing their "deep homology". We also
      confirm some other principles of Carroll's "Genetic theory of Morphological
      Evolution", such as "mosaic pleiotropy", exemplified by the dual role of Sox2
      reflected in its regulatory region. CONCLUSIONS: We were able to elucidate some
      aspects of the evolution of gene regulation for three genes associated with
      pluripotency. Based on the expected return on investment for the community, we
      encourage other scientists to contribute experimental data on gene regulation
      (original work as well as data collected for reviews) to the UCSC system, to
      enable studies of the evolution of gene regulation on a large scale, and to
      report their findings.

PMID- 21190563
TI  - Differential expression of protein kinase C isoforms in coronary arteries of
      diabetic mice lacking the G-protein Galpha11.
AB  - BACKGROUND: Diabetes mellitus counts as a major risk factor for developing
      atherosclerosis. The activation of protein kinase C (PKC) is commonly known to
      take a pivotal part in the pathogenesis of atherosclerosis, though the influence
      of specific PKC isozymes remains unclear. There is evidence from large clinical
      trials suggesting excessive neurohumoral stimulation, amongst other pathways
      leading to PKC activation, as a central mechanism in the pathogenesis of diabetic
      heart disease. The present study was therefore designed to determine the role of
      Gq-protein signalling via Galpha11 in diabetes for the expression of PKC isozymes
      in the coronary vessels. METHODS: The role of Galpha11 in diabetes was examined
      in knockout mice with global deletion of Galpha11 compared to wildtype controls.
      An experimental type 1-diabetes was induced in both groups by injection of
      streptozotocin. Expression and localization of the PKC isozymes alpha, betaII,
      delta, epsilon, and zeta was examined by quantitative immunohistochemistry.
      RESULTS: 8 weeks after induction of diabetes a diminished expression of PKC
      epsilon was observed in wildtype animals. This alteration was not seen in
      Galpha11 knockout animals, however, these mice showed a diminished expression of
      PKCzeta. Direct comparison of wildtype and knockout control animals revealed a
      diminished expression of PKC delta and epsilon in Galpha11 knockout animals.
      CONCLUSION: The present study shows that expression of the nPKCs delta and
      epsilon in coronary vessels is under control of the g-protein Galpha11. The
      reduced expression of PKC zeta that we observed in coronary arteries from
      Galpha11-knockout mice compared to wildtype controls upon induction of diabetes
      could reduce apoptosis and promote plaque stability. These findings suggest a
      mechanism that may in part underlie the therapeutic benefit of RAS inhibition on
      cardiovascular endpoints in diabetic patients.

PMID- 21190564
TI  - Sickness presenteeism in Spanish-born and immigrant workers in Spain.
AB  - BACKGROUND: Previous studies have shown that immigrant workers face relatively
      worse working and employment conditions, as well as lower rates of sickness
      absence than native-born workers. This study aims to assess rates of sickness
      presenteeism in a sample of Spanish-born and foreign-born workers according to
      different characteristics. METHODS: A cross-sectional survey was conducted
      amongst a convenience sample of workers (Spanish-born and foreign-born), living
      in four Spanish cities: Barcelona, Huelva, Madrid and Valencia (2008-2009).
      Sickness presenteeism information was collected through two items in the
      questionnaire ("Have you had health problems in the last year?" and "Have you
      ever had to miss work for any health problem?") and was defined as worker who had
      a health problem (answered yes, first item) and had not missed work (answered no,
      second item). For the analysis, the sample of 2,059 workers (1,617 foreign-born)
      who answered yes to health problems was included. After descriptives, logistic
      regressions were used to establish the association between origin country and
      sickness presenteeism (adjusted odds ratios aOR; 95% confidence interval 95%CI).
      Analyses were stratified per time spent in Spain among foreign-born workers.
      RESULTS: All of the results refer to the comparison between foreign-born and
      Spanish-born workers as a whole, and in some categories relating to personal and
      occupational conditions. Foreign-born workers were more likely to report sickness
      presenteeism compared with their Spanish-born counterparts, especially those
      living in Spain for under 2 years [Prevalence: 42% in Spanish-born and 56.3% in
      Foreign-born; aOR 1.77 95%CI 1.24-2.53]. In case of foreign-born workers (with
      time in Spain < 2 years), men [aOR 2.31 95%CI 1.40-3.80], those with university
      studies [aOR 3.01 95%CI 1.04-8.69], temporary contracts [aOR 2.26 95%CI 1.29
      3.98] and salaries between 751-1,200? per month [aOR 1.74 95% CI 1.04-2.92] were
      more likely to report sickness presenteeism. Also, recent immigrants with good
      self-perceived health and good mental health were more likely to report
      presenteeism than Spanish-born workers with the same good health indicators.
      CONCLUSIONS: Immigrant workers report more sickness presenteeism than their
      Spanish-born counterparts. These results could be related to precarious work and
      employment conditions of immigrants. Immigrant workers should benefit from the
      same standards of social security, and of health and safety in the workplace that
      are enjoyed by Spanish workers.

PMID- 21190565
TI  - Curvature recognition and force generation in phagocytosis.
AB  - BACKGROUND: The uptake of particles by actin-powered invagination of the plasma
      membrane is common to protozoa and to phagocytes involved in the immune response
      of higher organisms. The question addressed here is how a phagocyte may use
      geometric cues to optimize force generation for the uptake of a particle. We
      survey mechanisms that enable a phagocyte to remodel actin organization in
      response to particles of complex shape. RESULTS: Using particles that consist of
      two lobes separated by a neck, we found that Dictyostelium cells transmit signals
      concerning the curvature of a surface to the actin system underlying the plasma
      membrane. Force applied to a concave region can divide a particle in two,
      allowing engulfment of the portion first encountered. The phagosome membrane that
      is bent around the concave region is marked by a protein containing an inverse
      Bin-Amphiphysin-Rvs (I-BAR) domain in combination with an Src homology (SH3)
      domain, similar to mammalian insulin receptor tyrosine kinase substrate p53.
      Regulatory proteins enable the phagocyte to switch activities within seconds in
      response to particle shape. Ras, an inducer of actin polymerization, is activated
      along the cup surface. Coronin, which limits the lifetime of actin structures, is
      reversibly recruited to the cup, reflecting a program of actin depolymerization.
      The various forms of myosin-I are candidate motor proteins for force generation
      in particle uptake, whereas myosin-II is engaged only in retracting a phagocytic
      cup after a switch to particle release. Thus, the constriction of a phagocytic
      cup differs from the contraction of a cleavage furrow in mitosis. CONCLUSIONS:
      Phagocytes scan a particle surface for convex and concave regions. By modulating
      the spatiotemporal pattern of actin organization, they are capable of switching
      between different modes of interaction with a particle, either arresting at a
      concave region and applying force in an attempt to sever the particle there, or
      extending the cup along the particle surface to identify the very end of the
      object to be ingested. Our data illustrate the flexibility of regulatory
      mechanisms that are at the phagocyte's disposal in exploring an environment of
      irregular geometry.

PMID- 21190566
TI  - Matrix metalloproteinase-8 deficiency increases joint inflammation and bone
      erosion in the K/BxN serum-transfer arthritis model.
AB  - INTRODUCTION: Rheumatoid arthritis is an autoimmune disease in which joint
      inflammation leads to progressive cartilage and bone erosion. Matrix
      metalloproteinases (MMPs) implicated in homeostasis of the extracellular matrix
      play a central role in cartilage degradation. However, the role of specific MMPs
      in arthritis pathogenesis is largely unknown. The aim of the present study was to
      investigate the role of Mmp-8 (collagenase-2) in an arthritis model. METHODS:
      Arthritis was induced in Mmp8-deficient and wildtype mice by K/BxN serum
      transfer. Arthritis severity was measured by a clinical index and ankle sections
      were scored for synovial inflammation, cartilage damage and bone erosion. cDNA
      microarray analysis, real-time PCR and western blot were performed to identify
      differential changes in gene expression between mice lacking Mmp8 and controls.
      RESULTS: Mmp8 deficiency increased the severity of arthritis, although the
      incidence of disease was similar in control and deficient mice. Increased
      clinical score was associated with exacerbated synovial inflammation and bone
      erosion. We also found that the absence of Mmp8 led to increased expression of IL
      1beta, pentraxin-3 (PTX3) and prokineticin receptor 2 (PROKR2) in arthritic mice
      joints. CONCLUSIONS: Lack of Mmp-8 is accompanied by exacerbated synovial
      inflammation and bone erosion in the K/BxN serum-transfer arthritis model,
      indicating that this Mmp has a protective role in arthritis.

PMID- 21190567
TI  - Marked disability and high use of nonsteroidal antiinflammatory drugs associated
      with knee osteoarthritis in rural China: a cross-sectional population-based
      survey.
AB  - INTRODUCTION: The burden of disability, analgesia, and health services use
      associated with knee pain and osteoarthritis (OA) in developing countries is
      relatively unknown, despite a high proportion of these populations required to be
      engaged in heavy occupational physical activity throughout their life span. The
      aim of this survey was to estimate the burden of disability, analgesia, and
      health services use associated with knee pain in rural China. METHODS: This was a
      population-based cross-sectional survey among residents, aged 50 years and older,
      of Wuchuan County, Inner Mongolia. Participants completed an interviewer-based
      questionnaire, evaluating knee pain and associated disability, analgesia, and
      health services use, and obtained bilateral standardized weight-bearing knee
      radiographs. RESULTS: Of the 1,027 participants, 513 (50%) reported knee pain on
      most days of at least 1 month in the past year, with 109 (21%) also demonstrating
      radiographic OA (Kellgren-Lawrence grade >=2) in the symptomatic knee. Adjusting
      for age, gender, body mass index (BMI), education, and back pain, the presence of
      knee pain was associated with significantly greater difficulty in walking,
      climbing 10 steps, stooping, completing cleaning chores, and preparing meals.
      Among the 513 subjects with knee pain, the additional presence of radiographic
      evidence of OA was significantly associated with more occasions of "unbearable"
      pain (59% versus 36%) and restricted activity (64% versus 39%), as well as
      increased use of nonsteroidal antiinflammatory drugs (NSAIDs) (88% versus 78%)
      and the reported number of doctor visits (59% versus 33%) in the past year. The
      use of paracetamol for knee pain was rare (6% versus 2%). CONCLUSIONS: Knee pain
      is highly prevalent in rural northern China. The associated significant
      disability and marked preferential use of NSAIDs as analgesia should be of
      concern in these communities reliant on heavy occupational physical activity for
      their livelihood. The findings will be useful to guide the distribution of future
      health care resources and preventive strategies.

PMID- 21190568
TI  - Earthquake-related versus non-earthquake-related injuries in spinal injury
      patients: differentiation with multidetector computed tomography.
AB  - INTRODUCTION: In recent years, several massive earthquakes have occurred across
      the globe. Multidetector computed tomography (MDCT) is reliable in detecting
      spinal injuries. The purpose of this study was to compare the features of spinal
      injuries resulting from the Sichuan earthquake with those of non-earthquake
      related spinal trauma using MDCT. METHODS: Features of spinal injuries of 223
      Sichuan earthquake-exposed patients and 223 non-earthquake-related spinal injury
      patients were retrospectively compared using MDCT. The date of non-earthquake
      related spinal injury patients was collected from 1 May 2009 to 22 July 2009 to
      avoid the confounding effects of seasonal activity and clothing. We focused on
      anatomic sites, injury types and neurologic deficits related to spinal injuries.
      Major injuries were classified according to the grid 3-3-3 scheme of the Magerl
      (AO) classification system. RESULTS: A total of 185 patients (82.96%) in the
      earthquake-exposed cohort experienced crush injuries. In the earthquake and
      control groups, 65 and 92 patients, respectively, had neurologic deficits. The
      anatomic distribution of these two cohorts was significantly different (P <
      0.001). Cervical spinal injuries were more common in the control group (risk
      ratio (RR) = 2.12, P < 0.001), whereas lumbar spinal injuries were more common in
      the earthquake-related spinal injuries group (277 of 501 injured vertebrae;
      55.29%). The major types of injuries were significantly different between these
      cohorts (P = 0.002). Magerl AO type A lesions composed most of the lesions seen
      in both of these cohorts. Type B lesions were more frequently seen in earthquake
      related spinal injuries (RR = 1.27), while we observed type C lesions more
      frequently in subjects with non-earthquake-related spinal injuries (RR = 1.98, P
      = 0.0029). CONCLUSIONS: Spinal injuries sustained in the Sichuan earthquake were
      located mainly in the lumbar spine, with a peak prevalence of type A lesions and
      a high occurrence of neurologic deficits. The anatomic distribution and type of
      spinal injuries that varied between earthquake-related and non-earthquake-related
      spinal injury groups were perhaps due to the different mechanism of injury.

PMID- 21190569
TI  - Decrease in shunt volume in patients with cryptogenic stroke and patent foramen
      ovale.
AB  - BACKGROUND: In patients with patent foramen ovale (PFO) there is evidence
      supporting the hypothesis of a change in right-to-left shunt (RLS) over time.
      Proven, this could have implications for the care of patients with PFO and a
      history of stroke. The following study addressed this hypothesis in a cohort of
      patients with stroke and PFO. METHODS: The RLS volume assessed during
      hospitalisation for stroke (index event/T0) was compared with the RLS volume on
      follow-up (T1) (median time between T0 and T1 was 10 months). In 102 patients
      with a history of stroke and PFO the RLS volume was re-assessed on follow-up
      using contrast-enhanced transcranial Doppler/duplex (ce-TCD) ultrasound. A change
      in RLS volume was defined as a difference of >=20 microembolic signals (MES) or
      no evidence of RLS during ce-TCD ultrasound on follow-up. RESULTS: There was
      evidence of a marked reduction in RLS volume in 31/102 patients; in 14/31
      patients a PFO was no longer detectable. An index event classified as cryptogenic
      stroke (P < 0.001; OD = 39.2, 95% confidence interval 6.0 to 258.2) and the time
      interval to the follow-up visit (P = 0.03) were independently associated with a
      change in RLS volume over time. CONCLUSIONS: RLS volume across a PFO decreases
      over time, especially in patients with cryptogenic stroke. These may determine
      the development of new strategies for the management in the secondary stroke
      prevention.

PMID- 21190570
TI  - Individual vs. combinatorial effect of elevated CO2 conditions and salinity
      stress on Arabidopsis thaliana liquid cultures: comparing the early molecular
      response using time-series transcriptomic and metabolomic analyses.
AB  - BACKGROUND: In this study, we investigated the individual and combinatorial
      effect of elevated CO2 conditions and salinity stress on the dynamics of both the
      transcriptional and metabolic physiology of Arabidopsis thaliana liquid
      hydroponic cultures over the first 30 hours of continuous treatment. Both
      perturbations are of particular interest in plant and agro-biotechnological
      applications. Moreover, within the timeframe of this experiment, they are
      expected to affect plant growth to opposite directions. Thus, a major objective
      was to investigate whether this expected "divergence" was valid for the
      individual perturbations and to study how it is manifested under the combined
      stress at two molecular levels of cellular function, using high-throughput
      analyses. RESULTS: We observed that a) high salinity has stronger effect than
      elevated CO2 at both the transcriptional and metabolic levels, b) the
      transcriptional responses to the salinity and combined stresses exhibit strong
      similarity, implying a robust transcriptional machinery acting to the salinity
      stress independent of the co-occurrence of elevated CO2, c) the combinatorial
      effect of the two perturbations on the metabolic physiology is milder than of the
      salinity stress alone. Metabolomic analysis suggested that the beneficial role of
      elevated CO2 on salt-stressed plants within the timeframe of this study should be
      attributed to the provided additional resources; these allow the plants to
      respond to high salinity without having to forfeit other major metabolic
      functions, and d) 9 h-12 h and 24 h of treatment coincide with significant
      changes in the metabolic physiology under any of the investigated stresses.
      Significant differences between the acute and longer term responses were observed
      at both molecular levels. CONCLUSIONS: This study contributes large-scale dynamic
      omic data from two levels of cellular function for a plant system under various
      stresses. It provides an additional example of the power of integrated omic
      analyses for the comprehensive study of the molecular physiology of complex
      biological systems. Moreover, taking into consideration the particular interest
      of the two investigated perturbations in plant biotechnology, enhanced
      understanding of the molecular physiology of the plants under these conditions
      could lead to the design of novel metabolic engineering strategies to increase
      the resistance of commercial crops to salinity stress.

PMID- 21190571
TI  - The incidence of hip, forearm, humeral, ankle, and vertebral fragility fractures
      in Italy: results from a 3-year multicenter study.
AB  - INTRODUCTION: We aimed to assess the incidence and hospitalization rate of hip
      and "minor" fragility fractures in the Italian population. METHODS: We carried
      out a 3-year survey at 10 major Italian emergency departments to evaluate the
      hospitalization rate of hip, forearm, humeral, ankle, and vertebral fragility
      fractures in people 45 years or older between 2004 and 2006, both men and women.
      These data were compared with those recorded in the national hospitalizations
      database (SDO) to assess the overall incidence of fragility fractures occurring
      at hip and other sites, including also those events not resulting in hospital
      admissions. RESULTS: We observed 29,017 fractures across 3 years, with
      hospitalization rates of 93.0% for hip fractures, 36.3% for humeral fractures,
      31.3% for ankle fractures, 22.6% for forearm/wrist fractures, and 27.6% for
      clinical vertebral fractures. According to the analyses performed with the
      Italian hospitalization database in year 2006, we estimated an annual incidence
      of 87,000 hip, 48,000 humeral, 36,000 ankle, 85,000 wrist, and 155,000 vertebral
      fragility fractures in people aged 45 years or older (thus resulting in almost
      410,000 new fractures per year). Clinical vertebral fractures were recorded in
      47,000 events per year. CONCLUSIONS: The burden of fragility fractures in the
      Italian population is very high and calls for effective preventive strategies.

PMID- 21190572
TI  - HIV, appendectomy and postoperative complications at a reference hospital in
      Northwest Tanzania: cross-sectional study.
AB  - BACKGROUND: Appendicitis is a frequent surgical emergency worldwide. The present
      study was conducted to determine the prevalence of HIV, and the association of
      infection with clinical, intraoperative and histological findings and outcome,
      among patients with appendicitis. METHODS: We performed a cross sectional study
      at Weill-Bugando Medical Centre in northwest Tanzania. In total, 199 patients
      undergoing appendectomy were included. Demographic characteristics of patients,
      clinical features, laboratory, intraoperative and histopathological findings, and
      HIV serostatus were recorded. RESULTS: In total, 26/199 (13.1%) were HIV
      seropositive. The HIV-positive population was significantly older (mean age: 38.4
      years) than the HIV-negative population (25.3 years; p < 0.001). Leukocytosis was
      present in 87% of seronegative patients, as compared to 34% in seropositive
      patients (p = 0.0001), and peritonitis was significantly more frequent among HIV
      positives (31% vs. 2%; p < 0.001). The mean (SD) length of hospital stay was
      significantly longer in HIV-positives (7.12 +/- 2.94 days vs. 4.02 +/- 1.14 days;
      p < 0.001); 11.5% of HIV patients developed surgical site infections, as compared
      to 0.6% in the HIV-negative group (p = 0.004). CONCLUSION: HIV infections are
      common among patients with appendicitis in Tanzania, and are associated with
      severe morbidity, postoperative complications and longer hospital stays. Early
      diagnosis of appendicitis and prompt appendectomy are crucial in areas with high
      prevalence of HIV infection. Routine pre-test counseling and HIV screening for
      appendicitis patients is recommended to detect early cases who may benefit from
      HAART.

PMID- 21190573
TI  - BiologicalNetworks 2.0--an integrative view of genome biology data.
AB  - BACKGROUND: A significant problem in the study of mechanisms of an organism's
      development is the elucidation of interrelated factors which are making an impact
      on the different levels of the organism, such as genes, biological molecules,
      cells, and cell systems. Numerous sources of heterogeneous data which exist for
      these subsystems are still not integrated sufficiently enough to give researchers
      a straightforward opportunity to analyze them together in the same frame of
      study. Systematic application of data integration methods is also hampered by a
      multitude of such factors as the orthogonal nature of the integrated data and
      naming problems. RESULTS: Here we report on a new version of BiologicalNetworks,
      a research environment for the integral visualization and analysis of
      heterogeneous biological data. BiologicalNetworks can be queried for properties
      of thousands of different types of biological entities (genes/proteins,
      promoters, COGs, pathways, binding sites, and other) and their relations
      (interactions, co-expression, co-citations, and other). The system includes the
      build-pathways infrastructure for molecular interactions/relations and module
      discovery in high-throughput experiments. Also implemented in BiologicalNetworks
      are the Integrated Genome Viewer and Comparative Genomics Browser applications,
      which allow for the search and analysis of gene regulatory regions and their
      conservation in multiple species in conjunction with molecular pathways/networks,
      experimental data and functional annotations. CONCLUSIONS: The new release of
      BiologicalNetworks together with its back-end database introduces extensive
      functionality for a more efficient integrated multi-level analysis of microarray,
      sequence, regulatory, and other data. BiologicalNetworks is freely available at
      http://www.biologicalnetworks.org.

PMID- 21190574
TI  - Cognitive behavioural therapy versus supportive therapy for persistent positive
      symptoms in psychotic disorders: the POSITIVE Study, a multicenter, prospective,
      single-blind, randomised controlled clinical trial.
AB  - BACKGROUND: It has been demonstrated that cognitive behavioural therapy (CBT) has
      a moderate effect on symptom reduction and on general well being of patients
      suffering from psychosis. However, questions regarding the specific efficacy of
      CBT, the treatment safety, the cost-effectiveness, and the moderators and
      mediators of treatment effects are still a major issue. The major objective of
      this trial is to investigate whether CBT is specifically efficacious in reducing
      positive symptoms when compared with non-specific supportive therapy (ST) which
      does not implement CBT-techniques but provides comparable therapeutic attention.
      METHODS/DESIGN: The POSITIVE study is a multicenter, prospective, single-blind,
      parallel group, randomised clinical trial, comparing CBT and ST with respect to
      the efficacy in reducing positive symptoms in psychotic disorders. CBT as well as
      ST consist of 20 sessions altogether, 165 participants receiving CBT and 165
      participants receiving ST. Major methodological aspects of the study are
      systematic recruitment, explicit inclusion criteria, reliability checks of
      assessments with control for rater shift, analysis by intention to treat, data
      management using remote data entry, measures of quality assurance (e.g. on-site
      monitoring with source data verification, regular query process), advanced
      statistical analysis, manualized treatment, checks of adherence and competence of
      therapists. Research relating the psychotherapy process with outcome,
      neurobiological research addressing basic questions of delusion formation using
      fMRI and neuropsychological assessment and treatment research investigating
      adaptations of CBT for adolescents is combined in this network. Problems of
      transfer into routine clinical care will be identified and addressed by a project
      focusing on cost efficiency. DISCUSSION: This clinical trial is part of efforts
      to intensify psychotherapy research in the field of psychosis in Germany, to
      contribute to the international discussion on psychotherapy in psychotic
      disorders, and to help implement psychotherapy in routine care. Furthermore, the
      study will allow drawing conclusions about the mediators of treatment effects of
      CBT of psychotic disorders.

PMID- 21190575
TI  - HIV-1 gp120-mediated increases in IL-8 production in astrocytes are mediated
      through the NF-kappaB pathway and can be silenced by gp120-specific siRNA.
AB  - BACKGROUND: The exact mechanism underlying HIV-associated neurocognitive
      disorders still remains largely unresolved. However, viral genes (for example
      gp120 and tat) and their effect on cytokine/chemokine expressions have been
      linked with neuroinflammation. Conversely, interlekin-8 (IL-8) is a known
      proinflammatory chemokine and is known to be over-expressed in human brain
      microvascular endothelial cells in response to gp120. In this study, we sought to
      address whether HIV-1gp120 could affect IL-8 expression in astrocytes and whether
      the NF-kappaB pathway is involved in this phenomenon. METHODS: SVGA astrocytes
      were transfected with a plasmid expressing HIV-1 pSyn gp120 JR-FL using
      Lipofectamine2000. The cells were harvested at different time points after
      transfection, and total cellular RNA was used for quantification of IL-8 using a
      real time PCR. IL-8 protein expression was also determined in supernatants
      collected at different time points after transfection. Involvement of the NF
      kappaB pathway was addressed using both pharmacological inhibitors and an siRNA
      approach. In order to explore gene specificity, gp120-specific siRNAs were
      designed and IL-8 expression was monitored at both mRNA and protein levels.
      RESULTS: Gp120 increased IL-8 expression both at mRNA and protein levels by 7.1
      +/- 1.04 and 2.41 +/- 0.35 fold at 6 and 48 hours post-transfection,
      respectively. This increase was time-dependent and was abrogated by use of gp120
      specific siRNA. We have also shown that the NF-kappaB pathway is involved in
      gp120-mediated IL-8 overexpression as IKK-2 and IKKbeta inhibitors inhibited IL-8
      expression by 63.5% and 57.5%, respectively at the mRNA level, and by 67.3% and
      58.6% at the protein level. These results were also confirmed with use of NF
      kappaB-specific siRNA. CONCLUSION: These results indicate that gp120 can modulate
      expression of a pro-inflammatory chemokine (IL-8) in astrocytes in a time
      dependent manner with significant up-regulation at different times. This
      phenomenon is specific and is mediated by the NF-kappaB pathway.

PMID- 21190576
TI  - Plasma neuropeptide Y: a biomarker for symptom severity in chronic fatigue
      syndrome.
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) is a complex, multi-symptom illness
      with a multisystem pathogenesis involving alterations in the nervous, endocrine
      and immune systems.Abnormalities in stress responses have been identified as
      potential triggers or mediators of CFS symptoms. This study focused on the stress
      mediator neuropeptide Y (NPY). We hypothesized that NPY would be a useful
      biomarker for CFS. METHODS: The CFS patients (n = 93) were from the Chronic
      Fatigue and Related Disorders Clinic at the University of Miami and met the 1994
      case definition of Fukuda and colleagues. Healthy sedentary controls (n = 100))
      were from NIH or VA funded studies. Another fatiguing, multi-symptom illness,
      Gulf War Illness (GWI), was also compared to CFS. We measured NPY in plasma using
      a radioimmunoassay (RIA). Psychometric measures, available for a subset of CFS
      patients included: Perceived Stress Scale, Profile of Mood States, ATQ Positive &
      Negative Self-Talk Scores, the COPE, the Beck Depression Inventory, Fatigue
      Symptom Inventory, Cognitive Capacity Screening Examination, Medical Outcomes
      Survey Short Form-36, and the Quality of Life Scale. RESULTS: Plasma NPY was
      elevated in CFS subjects, compared to controls (p = .000) and to GWI cases (p =
      .000). Receiver operating characteristics (ROC) curve analyses indicated that the
      predictive ability of plasma NPY to distinguish CFS patients from healthy
      controls and from GWI was significantly better than chance alone. In 42 patients
      with CFS, plasma NPY had significant correlations (<0.05) with perceived stress,
      depression, anger/hostility, confusion, negative thoughts, positive thoughts,
      general health, and cognitive status. In each case the correlation (+ or -) was
      in the anticipated direction. CONCLUSIONS: This study is the first in the CFS
      literature to report that plasma NPY is elevated compared to healthy controls and
      to a fatigued comparison group, GWI patients. The significant correlations of NPY
      with stress, negative mood, general health, depression and cognitive function
      strongly suggest that this peptide be considered as a biomarker to distinguish
      subsets of CFS.

PMID- 21190577
TI  - Eag and HERG potassium channels as novel therapeutic targets in cancer.
AB  - Voltage gated potassium channels have been extensively studied in relation to
      cancer. In this review, we will focus on the role of two potassium channels,
      Ether a-go-go (Eag), Human ether a-go-go related gene (HERG), in cancer and their
      potential therapeutic utility in the treatment of cancer. Eag and HERG are
      expressed in cancers of various organs and have been implicated in cell cycle
      progression and proliferation of cancer cells. Inhibition of these channels has
      been shown to reduce proliferation both in vitro and vivo studies identifying
      potassium channel modulators as putative inhibitors of tumour progression. Eag
      channels in view of their restricted expression in normal tissue may emerge as
      novel tumour biomarkers.

PMID- 21190578
TI  - The role of catalase in pulmonary fibrosis.
AB  - BACKGROUND: Catalase is preferentially expressed in bronchiolar and alveolar
      epithelial cells, and acts as an endogenous antioxidant enzyme in normal lungs.
      We thus postulated epithelial damage would be associated with a functional
      deficiency of catalase during the development of lung fibrosis. METHODS: The
      present study evaluates the expression of catalase mRNA and protein in human
      interstitial pneumonias and in mouse bleomycin-induced lung injury. We examined
      the degree of bleomycin-induced inflammation and fibrosis in the mice with
      lowered catalase activity. RESULTS: In humans, catalase was decreased at the
      levels of activity, protein content and mRNA expression in fibrotic lungs (n =
      12) compared to control lungs (n = 10). Immunohistochemistry revealed a decrease
      in catalase in bronchiolar epithelium and abnormal re-epithelialization in
      fibrotic areas. In C57BL/6J mice, catalase activity was suppressed along with
      downregulation of catalase mRNA in whole lung homogenates after bleomycin
      administration. In acatalasemic mice, neutrophilic inflammation was prolonged
      until 14 days, and there was a higher degree of lung fibrosis in association with
      a higher level of transforming growth factor-beta expression and total collagen
      content following bleomycin treatment compared to wild-type mice. CONCLUSIONS:
      Taken together, these findings demonstrate diminished catalase expression and
      activity in human pulmonary fibrosis and suggest the protective role of catalase
      against bleomycin-induced inflammation and subsequent fibrosis.

PMID- 21190579
TI  - Genome-wide transcription profiling of human sepsis: a systematic review.
AB  - INTRODUCTION: Sepsis is thought to be an abnormal inflammatory response to
      infection. However, most clinical trials of drugs that modulate the inflammatory
      response of sepsis have been unsuccessful. Emerging genomic evidence shows that
      the host response in sepsis does not conform to a simple hyper-inflammatory/hypo
      inflammatory model. We, therefore, synthesized current genomic studies that
      examined the host response of circulating leukocytes to human sepsis. METHODS:
      Electronic searches were performed in Medline and Embase (1987 to October 2010),
      supplemented by additional searches in multiple microarray data repositories. We
      included studies that (1) used microarray, (2) were performed in humans and (3)
      investigated the host response mediated by circulating leukocytes. RESULTS: We
      identified 12 cohorts consisting of 784 individuals providing genome-wide
      expression data in early and late sepsis. Sepsis elicited an immediate activation
      of pathogen recognition receptors, accompanied by an increase in the activities
      of signal transduction cascades. These changes were consistent across most
      cohorts. However, changes in inflammation related genes were highly variable.
      Established inflammatory markers, such as tumour necrosis factor-alpha (TNF
      alpha), interleukin (IL)-1 or interleukin-10, did not show any consistent pattern
      in their gene-expression across cohorts. The finding remains the same even after
      the cohorts were stratified by timing (early vs. late sepsis), patient groups
      (paediatric vs. adult patients) or settings (clinical sepsis vs. endotoxemia
      model). Neither a distinctive pro/anti-inflammatory phase nor a clear transition
      from a pro-inflammatory to anti-inflammatory phase could be observed during
      sepsis. CONCLUSIONS: Sepsis related inflammatory changes are highly variable on a
      transcriptional level. We did not find strong genomic evidence that supports the
      classic two phase model of sepsis.

PMID- 21190580
TI  - Improving the iMM904 S. cerevisiae metabolic model using essentiality and
      synthetic lethality data.
AB  - BACKGROUND: Saccharomyces cerevisiae is the first eukaryotic organism for which a
      multi-compartment genome-scale metabolic model was constructed. Since then a
      sequence of improved metabolic reconstructions for yeast has been introduced.
      These metabolic models have been extensively used to elucidate the organizational
      principles of yeast metabolism and drive yeast strain engineering strategies for
      targeted overproductions. They have also served as a starting point and a
      benchmark for the reconstruction of genome-scale metabolic models for other
      eukaryotic organisms. In spite of the successive improvements in the details of
      the described metabolic processes, even the recent yeast model (i.e., iMM904)
      remains significantly less predictive than the latest E. coli model (i.e.,
      iAF1260). This is manifested by its significantly lower specificity in predicting
      the outcome of grow/no grow experiments in comparison to the E. coli model.
      RESULTS: In this paper we make use of the automated GrowMatch procedure for
      restoring consistency with single gene deletion experiments in yeast and extend
      the procedure to make use of synthetic lethality data using the genome-scale
      model iMM904 as a basis. We identified and vetted using literature sources 120
      distinct model modifications including various regulatory constraints for minimal
      and YP media. The incorporation of the suggested modifications led to a
      substantial increase in the fraction of correctly predicted lethal knockouts
      (i.e., specificity) from 38.84% (87 out of 224) to 53.57% (120 out of 224) for
      the minimal medium and from 24.73% (45 out of 182) to 40.11% (73 out of 182) for
      the YP medium. Synthetic lethality predictions improved from 12.03% (16 out of
      133) to 23.31% (31 out of 133) for the minimal medium and from 6.96% (8 out of
      115) to 13.04% (15 out of 115) for the YP medium. CONCLUSIONS: Overall, this
      study provides a roadmap for the computationally driven correction of multi
      compartment genome-scale metabolic models and demonstrates the value of synthetic
      lethals as curation agents.

PMID- 21190581
TI  - Population- and genome-specific patterns of linkage disequilibrium and SNP
      variation in spring and winter wheat (Triticum aestivum L.).
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) are ideally suited for the
      construction of high-resolution genetic maps, studying population evolutionary
      history and performing genome-wide association mapping experiments. Here, we used
      a genome-wide set of 1536 SNPs to study linkage disequilibrium (LD) and
      population structure in a panel of 478 spring and winter wheat cultivars
      (Triticum aestivum) from 17 populations across the United States and Mexico.
      RESULTS: Most of the wheat oligo pool assay (OPA) SNPs that were polymorphic
      within the complete set of 478 cultivars were also polymorphic in all
      subpopulations. Higher levels of genetic differentiation were observed among
      wheat lines within populations than among populations. A total of nine
      genetically distinct clusters were identified, suggesting that some of the pre
      defined populations shared significant proportion of genetic ancestry. Estimates
      of population structure (F(ST)) at individual loci showed a high level of
      heterogeneity across the genome. In addition, seven genomic regions with elevated
      F(ST) were detected between the spring and winter wheat populations. Some of
      these regions overlapped with previously mapped flowering time QTL. Across all
      populations, the highest extent of significant LD was observed in the wheat D
      genome, followed by lower LD in the A- and B-genomes. The differences in the
      extent of LD among populations and genomes were mostly driven by differences in
      long-range LD ( > 10 cM). CONCLUSIONS: Genome- and population-specific patterns
      of genetic differentiation and LD were discovered in the populations of wheat
      cultivars from different geographic regions. Our study demonstrated that the
      estimates of population structure between spring and winter wheat lines can
      identify genomic regions harboring candidate genes involved in the regulation of
      growth habit. Variation in LD suggests that breeding and selection had a
      different impact on each wheat genome both within and among populations. The
      higher extent of LD in the wheat D-genome versus the A- and B-genomes likely
      reflects the episodes of recent introgression and population bottleneck
      accompanying the origin of hexaploid wheat. The assessment of LD and population
      structure in this assembled panel of diverse lines provides critical information
      for the development of genetic resources for genome-wide association mapping of
      agronomically important traits in wheat.

PMID- 21190582
TI  - The maize ALDH protein superfamily: linking structural features to functional
      specificities.
AB  - BACKGROUND: The completion of maize genome sequencing has resulted in the
      identification of a large number of uncharacterized genes. Gene annotation and
      functional characterization of gene products are important to uncover novel
      protein functionality. RESULTS: In this paper, we identify, and annotate members
      of all the maize aldehyde dehydrogenase (ALDH) gene superfamily according to the
      revised nomenclature criteria developed by ALDH Gene Nomenclature Committee
      (AGNC). The maize genome contains 24 unique ALDH sequences encoding members of
      ten ALDH protein families including the previously identified male fertility
      restoration RF2A gene, which encodes a member of mitochondrial class 2 ALDHs.
      Using computational modeling analysis we report here the identification, the
      physico-chemical properties, and the amino acid residue analysis of a novel
      tunnel like cavity exclusively found in the maize sterility restorer protein,
      RF2A/ALDH2B2 by which this protein is suggested to bind variably long chain
      molecular ligands and/or potentially harmful molecules. CONCLUSIONS: Our finding
      indicates that maize ALDH superfamily is the most expanded of plant ALDHs ever
      characterized, and the mitochondrial maize RF2A/ALDH2B2 is the only plant ALDH
      that harbors a newly defined pocket/cavity with suggested functional specificity.

PMID- 21190583
TI  - Ethnographic study of ICT-supported collaborative work routines in general
      practice.
AB  - BACKGROUND: Health informatics research has traditionally been dominated by
      experimental and quasi-experimental designs. An emerging area of study in
      organisational sociology is routinisation (how collaborative work practices
      become business-as-usual). There is growing interest in the use of ethnography
      and other in-depth qualitative approaches to explore how collaborative work
      routines are enacted and develop over time, and how electronic patient records
      (EPRs) are used to support collaborative work practices within organisations.
      METHODS/DESIGN: Following Feldman and Pentland, we will use 'the organisational
      routine' as our unit of analysis. In a sample of four UK general practices, we
      will collect narratives, ethnographic observations, multi-modal (video and screen
      capture) data, documents and other artefacts, and analyse these to map and
      compare the different understandings and enactments of three common routines
      (repeat prescribing, coding and summarising, and chronic disease surveillance)
      which span clinical and administrative spaces and which, though 'mundane', have
      an important bearing on quality and safety of care. In a detailed qualitative
      analysis informed by sociological theory, we aim to generate insights about how
      complex collaborative work is achieved through the process of routinisation in
      healthcare organisations. DISCUSSION: Our study offers the potential not only to
      identify potential quality failures (poor performance, errors, failures of
      coordination) in collaborative work routines but also to reveal the hidden work
      and workarounds by front-line staff which bridge the model-reality gap in EPR
      technologies and via which "automated" safety features have an impact in
      practice.

PMID- 21190584
TI  - What's in a message? Delivering sexual health promotion to young people in
      Australia via text messaging.
AB  - BACKGROUND: Advances in communication technologies have dramatically changed how
      individuals access information and communicate. Recent studies have found that
      mobile phone text messages (SMS) can be used successfully for short-term
      behaviour change. However there is no published information examining the
      acceptability, utility and efficacy of different characteristics of health
      promotion SMS. This paper presents the results of evaluation focus groups among
      participants who received twelve sexual health related SMS as part of a study
      examining the impact of text messaging for sexual health promotion to on young
      people in Victoria, Australia. METHODS: Eight gender-segregated focus groups were
      held with 21 males and 22 females in August 2008. Transcripts of audio recordings
      were analysed using thematic analysis. Data were coded under one or more themes.
      RESULTS: Text messages were viewed as an acceptable and 'personal' means of
      health promotion, with participants particularly valuing the informal language.
      There was a preference for messages that were positive, relevant and short and
      for messages to cover a variety of topics. Participants were more likely to
      remember and share messages that were funny, rhymed and/or tied into particular
      annual events. The message broadcasting, generally fortnightly on Friday
      afternoons, was viewed as appropriate. Participants said the messages provided
      new information, a reminder of existing information and reduced apprehension
      about testing for sexually transmitted infections. CONCLUSIONS: Mobile phones, in
      particular SMS, offer health promoters an exciting opportunity to engage
      personally with a huge number of individuals for low cost. The key elements
      emerging from this evaluation, such as message style, language and broadcast
      schedule are directly relevant to future studies using SMS for health promotion,
      as well as for future health promotion interventions in other mediums that
      require short formats, such as social networking sites.

PMID- 21190585
TI  - Menstrual irregularity and bone mass in premenopausal women: cross-sectional
      associations with testosterone and SHBG.
AB  - BACKGROUND: There have been few studies examining the associations between
      menstrual irregularity, androgens and bone mass in population-based samples of
      premenopausal women. This study aimed to describe the associations between
      menstrual pattern, testosterone, sex hormone binding globulin (SHBG) and bone
      mass in a population-based sample of premenopausal women. METHODS: Cross
      sectional study (N = 382, mean age 31.5 years). Menstrual pattern was assessed by
      questionnaire, bone mass measured by quantitative ultrasound (QUS) and androgen
      status was assessed by levels of serum testosterone, SHBG and the free androgen
      index (FAI). RESULTS: Women with irregular cycles (n = 41, 11%) had higher free
      androgen index (FAI, P = 0.01) and higher QUS measurements including speed of
      sound (SOS, 1%, P < 0.05), quantitative ultrasound index (QUI, 7%, p < 0.05), and
      broadband ultrasound attenuation (BUA, 7%, p = 0.10). These associations
      persisted after adjustment for age and body mass index (BMI). After further
      adjustment for hormonal factors (either testosterone, SHBG or FAI), the strength
      of the associations was moderately attenuated, however, women with irregular
      cycles still had a 6% increase in mean QUS. Total testosterone, FAI and SHBG were
      also associated with QUS measures (testosterone and FAI, r +0.11 to +0.21, all p
      < 0.05; SHBG r -0.14 to -0.16, all p < 0.05) and the associations remained
      significant after adjustment. CONCLUSION: Irregular menstrual cycles were
      associated with higher bone mass in this population-based sample of premenopausal
      women suggesting menstrual disturbance should continue to be evaluated but may be
      less harmful for bone mass. The association between menstrual irregularity and
      bone mass was partially mediated by markers of androgen status especially free
      testosterone.

PMID- 21190586
TI  - Spread of porcine circovirus associated disease (PCVAD) in Ontario (Canada) swine
      herds: Part II. Matched case-control study.
AB  - BACKGROUND: The emergence of porcine circovirus associated disease (PCVAD) was
      associated with high mortality in swine populations worldwide. Studies performed
      in different regions identified spatial, temporal, and spatio-temporal trends as
      factors contributing to patterns of the disease spread. Patterns consistent with
      spatial trend and spatio-temporal clustering were already identified in this
      dataset. On the basis of these results, we have further investigated the nature
      of local spread in this report. The primary objective of this study was to
      evaluate risk factors for incidence cases of reported PCVAD. RESULTS: A time
      matched case-control study was used as a study design approach, and conditional
      logistic regression as the analytical method. The main exposure of interest was
      local spread, which was defined as an unidentified mechanism of PCVAD spread
      between premises located within 3 kilometers of the Euclidean distance. Various
      modifications of variables indicative of local spread were also evaluated. The
      dataset contained 278 swine herds from Ontario originally sampled either from
      diagnostic laboratory submissions or directly from the target population. A PCVAD
      case was defined on the basis of the producer's recall. Existence of apparent
      local spread over the entire study period was confirmed (OR = 2.26, 95% CI: 1.06,
      4.83), and was further identified to be time-varying in nature - herds
      experiencing outbreaks in the later part of the epidemic were more likely than
      control herds to be exposed to neighboring herds experiencing recent PCVAD
      outbreaks. More importantly, the pattern of local spread was driven by concurrent
      occurrence of PCVAD on premises under the same ownership (OREXACTwithin ownership
      = 25.6, 95% CI: 3.4, +inf; OREXACToutside ownership = 1.3, 95% CI: 0.45, 3.3).
      Other significant factors included PRRSv status of a herd (OREXACT = 1.9, 95% CI:
      1.0, 3.9), after adjusting for geographical location by including the binary
      effect of the easting coordinate (Easting > 600 km = 1; OREXACT = 1.8, 95% CI:
      0.5, 5.6). CONCLUSIONS: These results preclude any conclusion regarding the
      existence of a mechanism of local spread through airborne transmission or
      indirectly through contaminated fomites or vectors, as simultaneous emergence of
      PCVAD could also be a result of concurrent change in contributing factors due to
      other mechanisms within ownerships.

PMID- 21190587
TI  - Spread of porcine circovirus associated disease (PCVAD) in Ontario (Canada) swine
      herds: Part I. Exploratory spatial analysis.
AB  - BACKGROUND: The systemic form of porcine circovirus associated disease (PCVAD),
      also known as postweaning multisystemic wasting syndrome (PMWS) was initially
      detected in the early 1990s. Starting in 2004, the Canadian swine industry
      experienced considerable losses due to PCVAD, concurrent with a shift in genotype
      of porcine circovirus type 2 (PCV2). Objectives of the current study were to
      explore spatial characteristics of self-reported PCVAD distribution in Ontario
      between 2004 and 2008, and to investigate the existence and nature of local
      spread. RESULTS: The study included 278 swine herds from a large disease
      monitoring project that included porcine reproductive and respiratory syndrome
      (PRRS) virus-positive herds identified by the diagnostic laboratory, and PRRS
      virus-negative herds directly from the target population. Herds were included if
      they had growing pigs present on-site and available geographical coordinates for
      the sampling site. Furthermore, herds were defined as PCVAD-positive if a
      producer reported an outbreak of circovirus associated disease, or as PCVAD
      negative if no outbreak was noted. Spatial trend was investigated using
      generalized additive models and time to PCVAD outbreak in a herd using Cox's
      proportional hazard model; spatial and spatio-temporal clustering was explored
      using K-functions; and location of most likely spatial and spatio-temporal
      clusters was investigated using scan statistics. Over the study period, the risk
      of reporting a PCVAD-positive herd tended to be higher in the eastern part of the
      province after adjustment for herd PRRS status (P = 0.05). This was partly
      confirmed for spread (Partial P < 0.01). Local spread also appeared to exist, as
      suggested by the tentative (P = 0.06) existence of spatio-temporal clustering of
      PCVAD and detection of a spatio-temporal cluster (P = 0.04). CONCLUSIONS: In
      Ontario, PCVAD has shown a general trend, spreading from east-to-west. We
      interpret the existence of spatio-temporal clustering as evidence of spatio
      temporal aggregation of PCVAD-positive cases above expectations and, together
      with the existence of spatio-temporal and spatial clusters, as suggestive of
      apparent local spread of PCVAD. Clustering was detected at small spatial and
      temporal scales. Other patterns of spread could not be detected; however,
      survival rates in discrete Ontario zones, as well as a lack of a clear spatial
      pattern in the most likely spatio-temporal clusters, suggest other between-herd
      transmission mechanisms.

PMID- 21190588
TI  - HvCEBiP, a gene homologous to rice chitin receptor CEBiP, contributes to basal
      resistance of barley to Magnaporthe oryzae.
AB  - BACKGROUND: Rice CEBiP recognizes chitin oligosaccharides on the fungal cell
      surface or released into the plant apoplast, leading to the expression of plant
      disease resistance against fungal infection. However, it has not yet been
      reported whether CEBiP is actually required for restricting the growth of fungal
      pathogens. Here we evaluated the involvement of a putative chitin receptor gene
      in the basal resistance of barley to the ssd1 mutant of Magnaporthe oryzae, which
      induces multiple host defense responses. RESULTS: The mossd1 mutant showed
      attenuated pathogenicity on barley and appressorial penetration was restricted by
      the formation of callose papillae at attempted entry sites. When conidial
      suspensions of mossd1 mutant were spotted onto the leaves of HvCEBiP-silenced
      plants, small brown necrotic flecks or blast lesions were produced but these
      lesions did not expand beyond the inoculation site. Wild-type M. oryzae also
      produced slightly more severe symptoms on the leaves of HvCEBiP-silenced plants.
      Cytological observation revealed that these lesions resulted from appressorium
      mediated penetration into plant epidermal cells. CONCLUSIONS: These results
      suggest that HvCEBiP is involved in basal resistance against appressorium
      mediated infection and that basal resistance might be triggered by the
      recognition of chitin oligosaccharides derived from M. oryzae.

PMID- 21190589
TI  - Mitochondrial and endoplasmic reticulum stress pathways cooperate in zearalenone
      induced apoptosis of human leukemic cells.
AB  - BACKGROUND: Zearalenone (ZEA) is a phytoestrogen from Fusarium species. The aims
      of the study was to identify mode of human leukemic cell death induced by ZEA and
      the mechanisms involved. METHODS: Cell cytotoxicity of ZEA on human leukemic HL
      60, U937 and peripheral blood mononuclear cells (PBMCs) was performed by using 3
      (4,5-dimethyl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Reactive oxygen
      species production, cell cycle analysis and mitochondrial transmembrane potential
      reduction was determined by employing 2',7'-dichlorofluorescein diacetate,
      propidium iodide and 3,3'-dihexyloxacarbocyanine iodide and flow cytometry,
      respectively. Caspase-3 and -8 activities were detected by using fluorogenic Asp
      Glu-Val-Asp-7-amino-4-methylcoumarin (DEVD-AMC) and Ile-Glu-Thr-Asp-7-amino-4
      methylcoumarin (IETD-AMC) substrates, respectively. Protein expression of
      cytochrome c, Bax, Bcl-2 and Bcl-xL was performed by Western blot. The expression
      of proteins was assessed by two-dimensional polyacrylamide gel-electrophoresis
      (PAGE) coupled with LC-MS2 analysis and real-time reverse transcription
      polymerase chain reaction (RT-PCR) approach. RESULTS: ZEA was cytotoxic to U937 >
      HL-60 > PBMCs and caused subdiploid peaks and G1 arrest in both cell lines.
      Apoptosis of human leukemic HL-60 and U937 cell apoptosis induced by ZEA was via
      an activation of mitochondrial release of cytochrome c through mitochondrial
      transmembrane potential reduction, activation of caspase-3 and -8, production of
      reactive oxygen species and induction of endoplasmic reticulum stress. Bax was up
      regulated in a time-dependent manner and there was down regulation of Bcl-xL
      expression. Two-dimensional PAGE coupled with LC-MS2 analysis showed that ZEA
      treatment of HL-60 cells produced differences in the levels of 22 membrane
      proteins such as apoptosis inducing factor and the ER stress proteins including
      endoplasmic reticulum protein 29 (ERp29), 78 kDa glucose-regulated protein, heat
      shock protein 90 and calreticulin, whereas only ERp29 mRNA transcript increased.
      CONCLUSION: ZEA induced human leukemic cell apoptosis via endoplasmic stress and
      mitochondrial pathway.

PMID- 21190590
TI  - The association between adiponectin, HDL-cholesterol and alpha1-antitrypsin-LDL
      in female subjects without metabolic syndrome.
AB  - BACKGROUND: Oxidized low-density lipoprotein (LDL) may act as an atheroprotective
      (anti-atherosclerotic) agent under some conditions. While the alpha1-antitrypsin
      (AT)-LDL complex is considered a type of oxidized LDL, its clinical relevance
      remains unknown. The aim of the present study was to investigate the association
      between AT-LDL and anti-atherosclerotic variables such as HDL-cholesterol and
      adiponectin in subjects with and without metabolic syndrome (MetS). METHODS: In
      asymptomatic females (n = 194; mean age, 54 years) who were divided into non-MetS
      (n = 108) and MetS groups (n = 86), the fasting levels of serum AT-LDL,
      adiponectin and glucose/lipid panels were measured, in addition to body mass
      index (BMI) and blood pressure. RESULTS: The MetS group showed significantly
      higher BMI, blood pressure, glucose and triglyceride levels as well as
      significantly lower levels of HDL-cholesterol and adiponectin than the non-MetS
      group. A multivariate-adjusted analysis revealed that in the non-MetS group, AT
      LDL was significantly, independently and positively correlated with adiponectin
      (beta = 0.297, P < 0.05), along with HDL-cholesterol (beta = 0.217, P < 0.05). In
      the MetS group, AT-LDL was significantly, independently and positively correlated
      with LDL-cholesterol only (beta = 0.342, P < 0.05). CONCLUSIONS: These data
      suggest that AT-LDL may exert anti-atherosclerotic effects in female subjects
      without MetS. More studies are required to clarify the clinical roles of AT-LDL
      in relation to the pathophysiology of MetS.

PMID- 21190591
TI  - Understanding protein evolutionary rate by integrating gene co-expression with
      protein interactions.
AB  - BACKGROUND: Among the many factors determining protein evolutionary rate, protein
      protein interaction degree (PPID) has been intensively investigated in recent
      years, but its precise effect on protein evolutionary rate is still heavily
      debated. RESULTS: We first confirmed that the correlation between protein
      evolutionary rate and PPID varies considerably across different protein
      interaction datasets. Specifically, because of the maximal inconsistency between
      yeast two-hybrid and other datasets, we reasoned that the difference in
      experimental methods contributes to our inability to clearly define how PPID
      affects protein evolutionary rate. To address this, we integrated protein
      interaction and gene co-expression data to derive a co-expressed protein-protein
      interaction degree (ePPID) measure, which reflects the number of partners with
      which a protein can permanently interact. Thus, irrespective of the experimental
      method employed, we found that (1) ePPID is a better predictor of protein
      evolutionary rate than PPID, (2) ePPID is a more robust predictor of protein
      evolutionary rate than PPID, and (3) the contribution of ePPID to protein
      evolutionary rate is statistically independent of expression level. Analysis of
      hub proteins in the Structural Interaction Network further supported ePPID as a
      better predictor of protein evolutionary rate than the number of distinct binding
      interfaces and clarified the slower evolution of co-expressed multi-interface hub
      proteins over that of other hub proteins. CONCLUSIONS: Our study firmly
      established ePPID as a robust predictor of protein evolutionary rate,
      irrespective of experimental method, and underscored the importance of permanent
      interactions in shaping the evolutionary outcome.

PMID- 21190593
TI  - Type 2 diabetes genetic association database manually curated for the study
      design and odds ratio.
AB  - BACKGROUND: The prevalence of type 2 diabetes has reached epidemic proportions
      worldwide, and the incidence of life-threatening complications of diabetes
      through continued exposure of tissues to high glucose levels is increasing.
      Advances in genotyping technology have increased the scale and accuracy of the
      genotype data so that an association genetic study has expanded enormously.
      Consequently, it is difficult to search the published association data
      efficiently, and several databases on the association results have been
      constructed, but these databases have their limitations to researchers: some
      providing only genome-wide association data, some not focused on the association
      but more on the integrative data, and some are not user-friendly. In this study,
      a user-friend database of type 2 diabetes genetic association of manually curated
      information was constructed. DESCRIPTION: The list of publications used in this
      study was collected from the HuGE Navigator, which is an online database of
      published genome epidemiology literature. Because type 2 diabetes genetic
      association database (T2DGADB) aims to provide specialized information on the
      genetic risk factors involved in the development of type 2 diabetes, 701 of the
      1,771 publications in the type 2 Diabetes case-control study for the development
      of the disease were extracted. CONCLUSIONS: In the database, the association
      results were grouped as either positive or negative. The gene and SNP names were
      replaced with gene symbols and rsSNP numbers, the association p-values were
      determined manually, and the results are displayed by graphs and tables. In
      addition, the study design in publications, such as the population type and size
      are described. This database can be used for research purposes, such as an
      association and functional study of type 2 diabetes related genes, and as a
      primary genetic resource to construct a diabetes risk test in the preparation of
      personalized medicine in the future.

PMID- 21190592
TI  - The physiological roles of vesicular GABA transporter during embryonic
      development: a study using knockout mice.
AB  - BACKGROUND: The vesicular GABA transporter (VGAT) loads GABA and glycine from the
      neuronal cytoplasm into synaptic vesicles. To address functional importance of
      VGAT during embryonic development, we generated global VGAT knockout mice and
      analyzed them. RESULTS: VGAT knockouts at embryonic day (E) 18.5 exhibited
      substantial increases in overall GABA and glycine, but not glutamate, contents in
      the forebrain. Electrophysiological recordings from E17.5-18.5 spinal cord
      motoneurons demonstrated that VGAT knockouts presented no spontaneous inhibitory
      postsynaptic currents mediated by GABA and glycine. Histological examination of
      E18.5 knockout fetuses revealed reductions in the trapezius muscle, hepatic
      congestion and little alveolar spaces in the lung, indicating that the
      development of skeletal muscle, liver and lung in these mice was severely
      affected. CONCLUSION: VGAT is fundamental for the GABA- and/or glycine-mediated
      transmission that supports embryonic development. VGAT knockout mice will be
      useful for further investigating the roles of VGAT in normal physiology and
      pathophysiologic processes.

PMID- 21190594
TI  - Transcription factor c-Myb promotes the invasion of hepatocellular carcinoma
      cells via increasing osteopontin expression.
AB  - BACKGROUND: Specific gene expression is tightly regulated by various
      transcription factors. Osteopontin (OPN) is a phosphoprotein that mediates
      hepatocellular carcinoma (HCC) progression and metastasis. However, the mechanism
      of OPN up-regulation in HCC metastasis remains to be clarified. METHODS:
      Oligonucleotide array-based transcription factor assays were applied to compare
      different activities of transcription factors in two human HCC cell lines with
      different OPN expression levels. The effects of one selected transcription factor
      on OPN expression were further evaluated. RESULTS: Eleven transcription factors
      were over-expressed in metastatic HCC cell line HCCLM6 cells whereas twelve
      transcription factors were down-regulated. Electrophoretic mobility shift assays
      (EMSA) and reporter gene assays showed that one of up-regulated transcription
      factors c-Myb could bind the OPN promoter and increase its transcription
      activity. In addition, small interfering RNA targeting c-Myb could inhibit OPN
      expression and significantly decrease migration and invasion of HCCLM6 cells in
      vitro. CONCLUSION: Our data first demonstrate that c-Myb has a functionally
      important role in the regulation of OPN expression in HCC cells, suggesting that
      c-Myb might be a new target to control HCC metastasis.

PMID- 21190595
TI  - [Analysis of the influencing factors of life quality in patients undergoing
      maintaining hemodialysis].
AB  - OBJECTIVE: To determine the influencing factors and life quality of patients
      undergoing maintaining hemodialysis (MHD). METHODS: One hundred and two MHD
      patients in hemodialysis center were enrolled, and a questionnaire investigation
      using KDQOL-SF(TM) 1.3 was employed. This questionnaire was disease-specific for
      chronic kidney disease. The object was to evaluate the quality of life, in
      relation with the patients' kidney disease and dialysis (KDTA) and the patients'
      general health (SF-36), and to analyze the influencing factors. RESULTS: Among
      the influencing factors revealed in questionnaire investigation, the items such
      as encouragement from medical staff, social support, symptoms, cognitive
      function, quality of social relationship and satisfaction degree of patients won
      higher scores, while the items such as sex function, difficulties in daily
      activity due to kidney disease, expectation of general health and self-evaluation
      of health won lower scores. Among the influencing factors, the scores of physical
      functions and body pain were much lower in female than male patients (63.52+/
      17.96 vs. 71.65+/-18.66, 64.33+/-21.23 vs. 76.58+/-19.20, both P<0.05). Patients
      of age>60 won higher scores than patients of age<=40 and 40-60 in respect to work
      condition and sex function (61.98+/-13.63 vs. 52.27+/-7.54 and 55.23+/-19.97,
      68.33+/-4.04 vs. 5.45+/-9.34 and 15.81+/-26.92, all P<0.05); patients of 60 years
      old or older won higher scores in respect of satisfaction degree of patients but
      lower scores in respect of physical functions. Among primary diseases, only
      patients with diabetes won much encouragement from medical staff (93.57+/-11.29).
      Patients whose serum albumin was lower than 3.5 g/L won much lower scores than
      those with serum albumin higher than 3.5 g/L in respect of scoring of KDTA,
      influence to daily life due to kidney disease, cognitive function, physical
      functions, expectation of general health, and scores obtained previously (53.62+/
      8.87 vs. 61.26+/-9.42, 44.58+/-12.52 vs. 57.47+/-17.15, 65.56+/-20.60 vs. 78.18+/
      15.73, 54.38+/-19.73 vs. 68.87+/-17.57, 31.11+/-10.23 vs. 41.19+/-66.27, 44.44+/
      27.06 vs. 68.57+/-26.94, all P<0.05). Patients who had undergone hemodialysis for
      longer than 6 years won higher scores in respect to symptoms, body pain, vigour
      and expectation of general health (86.92+/-6.67, 85.08+/-57.34, 78.40+/-13.04,
      53.33+/-24.22, respectively), while patients who had hemodialysis for as long as
      3 to 6 years won highest scores in respect to social support (94.23+/-10.96, all
      P<0.05). The level of hemoglobin and urea clearance index showed no obvious
      influence to MHD patients' daily life. CONCLUSION: MHD patients have poor self
      confidence and they usually lose self-confidence. Nutritional status greatly
      influences patients' daily life. So it is important to improve the quality of
      daily life in MHD patients, especially in respect of nutritional support, and
      this aspect should form our focus of medical support.

PMID- 21190596
TI  - [Construction of a novel bioreactor of bioartificial liver system with human bone
      marrow mesenchymal stem cells].
AB  - OBJECTIVE: To design a novel bioreactor of bioartificial liver system by using
      expanded and differentiated human bone marrow mesenchymal stem cells (hBMMSCs) as
      active cells. METHODS: hBMMSCs were isolated from bone marrow of volunteers and
      grown to 10(7) population, and then replanted into hollow fiber cartridge to
      expand continuously for 10 days. They were incubated in differentiation medium
      containing recombinant human hepatocyte growth factor (rhHGF), recombinant human
      fibroblast growth factor 4 (rhFGF-4), recombinant human oncostatin M (rhOSM), and
      the cells were induced to differentiate into hepatocyte-like cells for 21 days.
      The functions of the differentiated cells, such as synthesis of albumin (Alb),
      alpha fetoprotein (AFP) were determined. Eighteen days later, the functions of
      metabolism of ammonia and benzodiazepines, and synthesis of urea were monitored.
      The cellular synthesis rate of Alb was measured with flow cytometer. The glucose
      levels in the medium were measured during entire culture process. RESULTS:
      (1)Glucose-uptake in the cartridge was increased during the culture period, and
      at the end of culture, the number of cells in the cartridge increased to 10(9).
      (2)After induction, AFP was detected on day 6, reaching the peak level on day 12.
      Alb was detected on day 9. Eighteen days after being induced, the clearance rate
      of ammonia and benzodiazepines in the cartridge was 2.0-2.7 mmol/24 hours and 3.2
      3.8 mg/24 hours, respectively, and urea production rate was 1.8-2.2 mmol/24
      hours. (3)At the end of the culture, 66.18%-76.91% of the cells showed positive
      Alb expression. CONCLUSION: hBMMSCs can be multiply to construct a novel
      bioreactor of bioartificial liver system in a hollow fiber cartridge.

PMID- 21190597
TI  - [Clinical research of Dahuang Fuzi decoction in auxiliary treatment of severe
      acute pancreatitis: a multi-center observation in 206 patients].
AB  - OBJECTIVE: To observe the efficacy of Dahuang Fuzi decoction in patients with
      severe acute pancreatitis (SAP), and to provide valuable medical evidences for a
      treatment of SAP with combined traditional Chinese and western medicine. METHODS:
      A prospective, multi-center, randomized, controlled clinical trial was designed.
      Two hundred and six adult patients with SAP admitted to intensive care unit (ICU)
      in three tertiary university teaching hospitals in Dalian from January 2007 to
      February 2010 were randomly divided into two groups: soapsuds enema control group
      (control group, n=101) and Dahuang Fuzi decoction enema study group (study group,
      n=105). The levels of serum amylase, albumin (Alb), D-lactic acid, endotoxin and
      diamine oxidase (DAO), high-sensitive C-reactive protein (hs-CRP), immunoglobulin
      (IgG, IgA, IgM), complements (C3, C4), tumour necrosis factor-alpha (TNF-alpha),
      interleukins (IL-6, IL-8) were determined before and after treatment for 2, 4, 7
      days. The bowel sound, gastrointestinal function score, the acute physiology and
      chronic health evaluation II (APACHEII) score and the length of mechanical
      ventilation (MV), the length of stay in ICU, the mortality rate and average
      hospital expenses within 28 days were compared. RESULTS: Compared with control
      group, in the study group the levels of serum amylase, DAO, D-lactic acid and
      endotoxin were lowered, the Alb was increased, the levels of TNF-alpha, IL-6, IL
      8, hs-CRP were decreased, the function of body immunity was enhanced, intestinal
      peristalsis was enhanced, gastrointestinal function score and APACHEII score were
      improved, the length of MV was reduced, the length of stay in ICU was diminished,
      the 28-day mortality and average hospital expenses were lowered [4 days amylase
      (U/L): 357.35+/-137.54 vs. 492.95+/-189.42, 2 days DAO (kU/L) : 5.20+/-0.59 vs.
      5.45+/-0.72, 4 days D-lactic acid (mmol/L): 3.31+/-0.48 vs. 4.15+/-0.55, 2 days
      endotoxin (kEU/L): 0.29+/-0.11 vs. 0.34+/-0.14, 4 days Alb (g/L): 34.75+/-3.56
      vs. 32.53+/-3.44, 2 days TNF-alpha (ng/L): 3.08+/-0.45 vs. 3.36+/-1.11, 2 days IL
      6 (ng/L): 298.54+/-67.82 vs. 313.56+/-73.91, 4 days IL-8 (ng/L): 30.48+/-8.56 vs.
      45.16+/-10.81, 2 days hs-CRP (mg/L): 32.56+/-11.83 vs. 40.42+/-15.10, 4 days IgG
      (g/L): 7.05+/-2.56 vs. 9.53+/-2.94, 2 days IgA (mg/L): 1 600+/-170 vs. 1 400+/
      140, 4 days IgM (mg/L): 1 310+/-280 vs. 1 650+/-290, 4 days C3 (g/L): 1.11+/-0.09
      vs. 1.50+/-0.15, 4 days C4 (g/L) : 0.32+/-0.11 vs. 0.41+/-0.10, 2 days bowel
      sound (times/min): 1.26+/-0.45 vs. 1.15+/-0.41, 2 days gastrointestinal function
      score: 2.24+/-0.98 vs. 2.42+/-1.05, 4 days APACHEII score: 16.4+/-6.8 vs. 20.1+/
      7.1, the length of MV (days): 6.5+/-3.1 vs. 10.1+/-4.6, the length of stay in ICU
      (days): 11.3+/-6.3 vs. 13.8+/-7.5, mortality: 8.6% vs. 16.8%, average hospital
      expenses (yuan): 72 thousands vs. 86 thousands, P<0.05 or P<0.01]. CONCLUSION:
      Dahuang Fuzi decoction may enhance the intestinal peristalsis, protect the
      gastrointestinal barrier function, reduce the bacteria and endotoxin
      translocation and the releasing of inflammation mediators, protect the function
      of body immunity, reduce the length of MV, the length of stay in ICU, and lower
      the 28-day mortality and average hospital expenses, and it can improve the
      prognosis of patients with SAP.

PMID- 21190598
TI  - [Severe pulmonary infection following liver transplantation: a case report of
      successful treatment].

PMID- 21190599
TI  - [Study on the expression of uncoupling protein 2 in the kidney of the rats with
      hypothyroidism].
AB  - OBJECTIVE: To observe the change in the expression of uncoupling protein 2 (UCP2)
      in kidney mitochondria in rats with hypothyroidism, and study the mechanism of
      renal injury due to hypothyroidism. METHODS: The Wistar rats were randomly
      divided into control group (n=10) and hypothyroidism group (n=10). The
      hypothyroidism rat model was reproduced by low-iodine diet. The intake of iodine
      in control group and hypothyroidism group were 10.00 MUg/d and 1.24 MUg/d,
      respectively. The rats were raised under these conditions respectively for 3
      months after they adapted to the feeding for 1 week. Then the thyroid function
      parameters were measured in blood, and the expressions of UCP2 protein and mRNA
      in renal tissue were measured by immunohistochemistry and reverse transcription
      polymerase chain reaction (RT-PCR) methods. RESULTS: The thyrotropic-stimulating
      hormone (TSH, mU/L) in hypothyroidism group was significantly higher than that in
      control group (4.88+/-1.37 vs. 1.65+/-0.33, P<0.05). The levels of total
      triiodothyronine (TT(3)), total thyroxine (TT(4)), free triiodothyronine (FT(3))
      and free thyroxine (FT(4)) in serum in hypothyroidism group were significantly
      lower than those in control group [TT(3) (nmol/L) : 0.54+/-0.07 vs. 0.98+/-0.17,
      TT(4) (nmol/L): 7.82+/-2.18 vs. 48.78+/-3.65, FT(3) (pmol/L): 2.28+/-0.22 vs.
      2.99+/-0.10, FT(4) (pmol/L): 11.38+/-1.74 vs. 29.27+/-0.95, all P<0.01]. The
      immunohistochemistry study revealed that the UCP2 protein expression in both
      renal glomeruli and tubule tissues in the hypothyroidism group was significantly
      lower than that of control group (renal glomeruli: 0.17+/-0.02 vs. 0.24+/-0.04,
      renal tubule: 0.19+/-0.02 vs. 0.25+/-0.02, both P<0.01). The RT-PCR showed that
      the UCP2 mRNA expression in the hypothyroidism group was significantly lower than
      that of control group (0.70+/-0.19 vs. 1.30+/-0.09, P<0.01). CONCLUSION:
      Hypothyroidism may produce damage to kidney, which is related to the down
      regulation of UCP2 expression in the mitochondria of renal cells.

PMID- 21190600
TI  - [Mechanism of multiple organ injury subsequent to acute renal failure with
      respect to membrane pump activity in rabbits].
AB  - OBJECTIVE: To observe the changes in membrane pump activity of kidney, myocardium
      and pancreas in rabbits with acute renal failure (ARF) in rabbits, and inquire
      into the mechanism of multiple organ injury subsequent to ARF. METHODS: Forty-two
      rabbits were randomly divided into control group, HgCl(2) group and glycerine
      group, and the latter two groups were subdivided into 12, 24, 48-hour subgroups,
      with 6 rabbits in each group. The ARF model was reproduced by hypodermic
      injection 1% HgCl(2) (1.3 ml/kg) in HgCl(2) group, or intramuscularly injection
      50% glycerine (10 ml/kg) in glycerine group, respectively. At different time
      points, the kidney, myocardium and pancreas were harvested, and homogenates of
      them were prepared. The ATPase activities of different organ homogenates were
      determined. RESULTS: It showed that the activities of Na(+)-K(+)-ATPase, Ca(2+)
      ATPase, Ca(2+)-Mg(2+)-ATPase of renal homogenate in two model groups were reduced
      gradually with worsening of renal function, and they became lowest at 48 hours
      [(0.84+/-0.16), (0.52+/-0.17), (0.45+/-0.09) MUmol*mg(-1)*h(-1) in HgCl(2) group;
      (0.85+/-0.22), (0.49+/-0.21), (0.54+/-0.17) MUmol*mg(-1) *h(-1)in glycerine
      group]. The respective activities of Na (+)-K (+)-ATPase, Ca (2+)-ATPase, Mg(2+)
      ATPase, Ca(2+)-Mg(2+)-ATPase of myocardium and pancreas homogenates in two model
      groups were reduced gradually following depression of renal function, and they
      became lowest at 48 hours [(0.56+/-0.11), (0.51+/-0.19), (0.55+/-0.19), (0.37+/
      0.19) MUmol*mg(-1)*h(-1) in HgCl(2) group and (0.52+/-0.19), (0.62+/-0.10),
      (0.61+/-0.16), (0.54+/-0.10) MUmol*mg(-1) *h(-1) in myocardium homogenate of
      glycerine group; (0.81+/-0.12), (0.71+/-0.15), (0.73+/-0.18), (0.62+/-0.16)
      MUmol*mg(-1) *h(-1) in HgCl(2) group and (0.72+/-0.13), (0.57+/-0.18), (0.66+/
      0.14), (0.59+/-0.23) MUmol*mg(-1) *h(-1) in pancreas homogenate of glycerine
      group], there was statistical difference compared with control group (P<0.05 or
      P<0.01). CONCLUSION: The mechanism of myocardial and pancreatic injury subsequent
      to ARF might be related to reduction of the activity of cell membrane pump.

PMID- 21190601
TI  - [The effect of caspase-3 inhibitor on the concentrations of serum inflammatory
      cytokines in sepsis related acute kidney injury induced by peritoneal cavity
      infection in mice].
AB  - OBJECTIVE: To observe the effects of caspase-3 inhibitor Ac-DEVD-CHO on the
      concentrations of serum inflammatory cytokines in sepsis related acute kidney
      injury induced by peritoneal cavity infection in mice. METHODS: One hundred and
      two male C57BL/6 mice were subjected to cecal ligation and puncture (CLP, a model
      of polymicrobial sepsis) or sham operation. The animals were assigned into three
      equal groups (n=34) according to random number table: sham group, model group,
      and caspase-3 inhibitor (CI) group. Thirty minutes before CLP, Ac-DEVD-CHO (4
      MUg/g) was injected subcutaneously in CI group. The levels of blood urea nitrogen
      (BUN) and creatinine (Cr) were determined, and the concentrations of tumor
      necrosis factor-alpha (TNF-alpha), interleukins (IL-6 and IL-10) were measured by
      enzyme linked immunosorbent assay (ELISA), the renal cell apoptosis rate was
      determined by flow cytometry and the expression of caspase-3 mRNA was determined
      by real time reverse transcription-polymerase chain reaction (RT-PCR) at 6, 12
      and 24 hours after operation. The 4-day and 7-day survival rates of three groups
      of mice were observed. RESULTS: Compared with sham group, the concentrations of
      serum BUN, TNF-alpha, IL-6, IL-10 and the renal cell apoptosis rates, the caspase
      3 mRNA expression were increased significantly at all time points after CLP, the
      concentrations of serum Cr were increased significantly at 6 hours, with the 4
      day and 7-day survival rates were decreased significantly. Compared with model
      group, in CI group, the concentrations of serum BUN were decreased significantly
      at all time points after operation and those of Cr were decreased significantly
      at 6 hours, then restored to those of the sham group at 12 hours and 24 hours;
      the concentrations of serum TNF-alpha, IL-6 were decreased and those of IL-10
      elevated significantly at all time points [TNF-alpha (MUg/L) 6 hours: 436.2+/
      64.2 vs. 653.6+/-8.9, 12 hours: 233.4+/-85.4 vs. 579.7+/-137.1, 24 hours: 151.0+/
      90.3 vs. 551.0+/-119.8; IL-6 (MUg/L) 6 hours: 1 033.2+/-345.8 vs. 1 595.3+/
      159.4, 12 hours : 366.3+/-68.3 vs. 1 330.7+/-249.8, 24 hours: 241.2+/-208.4 vs.
      815.3+/-572.7; IL-10 (MUg/L) 6 hours : 33.6+/-10.4 vs. 26.6+/-4.5, 12 hours:
      37.2+/-5.0 vs. 24.5+/-4.3, 24 hours: 38.3+/-5.5 vs. 18.2+/-1.6, all P<0.05]; the
      renal cell apoptosis rate and the expression of caspase-3 mRNA were decreased
      significantly at all time points [apoptosis rates 6 hours: (13.9+/-3.2)% vs.
      (18.3+/-1.4)%, 12 hours: (10.5+/-3.6)% vs. (15.9+/-3.5)%, 24 hours: (8.4+/-1.8)%
      vs. (12.5+/-2.1)%; caspase-3 mRNA 6 hours: 1.95+/-0.16 vs. 3.84+/-0.35, 12 hours:
      1.89+/-0.19 vs. 3.97+/-0.73, 24 hours : 2.01+/-0.20 vs. 4.97+/-0.24, all P<0.05].
      The 4-day survival rate of CI group was improved (80% vs. 20%), but that of 7-day
      did not change (20% vs. 20%). CONCLUSION: The modulation of caspase-3 inhibitor
      on the concentrations of serum inflammatory cytokines in sepsis related acute
      kidney injury induced by peritoneal cavity infection may be associated with a
      decrease in renal cell apoptosis by Ac-DEVD-CHO.

PMID- 21190602
TI  - [Intervention role of lymph plasma on renal and hepatic blood perfusion in rats
      with endotoxic shock].
AB  - OBJECTIVE: To observe the intervention role of normal lymph plasma on renal and
      hepatic micro-regional blood perfusion in rats with endotoxic shock. METHODS:
      Thirty male Wistar rats were equally divided into control group, model group and
      lymph plasma group by random digits table. The latter two groups were injected
      intravenously with lipopolysaccharide (LPS, 15 mg/kg) to duplicate endotoxic
      shock model, and equal amount of normal saline was given in the control group
      instead of LPS. Fifteen minutes after the reproduction of model, normal lymph
      plasma in an amount of 1/15 of blood volume was infused in lymph plasma group. In
      control and model groups, normal saline was given instead of lymph plasma. Blood
      pressure was monitored continuously for 6 hours after LPS injection (or normal
      saline) in all groups, and the micro-regional blood perfusion of the kidney and
      liver was also observed at the same time with laser Doppler flowmetry. The
      survival time among groups was compared. RESULTS: After injecting LPS, the blood
      pressure of both model and lymph plasma groups declined quickly, and in model
      group, it gradually descended after a brief elevation. The blood pressure of
      lymph plasma group although was lower than that of control group at early and
      later stage, but it was still higher than that of model group. After LPS
      injection, the micro-regional blood perfusion (PU) of kidney and liver in model
      group and lymph plasma group were also decreased significantly compared with the
      control group (kidney: 559.90+/-111.87, 577.50+/-91.49 vs. 672.60+/-50.81; liver:
      160.50+/-54.17, 163.56+/-34.04 vs. 232.30+/-34.23, all P<0.05). The blood
      perfusion of kidney in two groups was increased markedly after 30 minutes
      compared with control group, and the high level was maintained in the lymph
      plasma group up to 75 minutes, then it maintained at the level of control group.
      However, in model group, the blood perfusion was significantly reduced at 120
      minutes, and it was significantly lower than control group after 210 minutes. The
      renal micro-regional blood perfusion (PU) in lymph plasma group was significantly
      higher than that of model group at 270-360 minutes, especially after 330 minutes
      (330 minutes : 615.44+/-98.71 vs. 364.40+/-146.76, 360 minutes: 584.56+/-104.72
      vs. 307.11+/-143.11, both P<0.05). The liver blood perfusion in both groups
      became normal at 30 minutes, and in model group it declined progressively at 270
      minutes. In lymph plasma group the liver blood perfusion (PU) was markedly
      increased compared with model group, especially after 330 minutes (330 minutes :
      224.67+/-20.65 vs. 172.90+/-46.74, 360 minutes: 218.56+/-20.40 vs. 158.52+/
      44.71, both P<0.05 ). In model group, the onset of decrease in perfusion
      (minutes) in the kidney was significantly earlier than that of liver (123.00+/
      68.85 vs. 282.00+/-96.90, P<0.01). Survival time (hours) was markedly prolonged
      in lymph plasma group than that of model group (11.80+/-2.67 vs. 7.21+/-1.33,
      P<0.01). CONCLUSION: Normal lymph plasma may play a beneficial intervention role
      in kidney and liver tissue hypoperfusion, and it ameliorates hypotension and
      prolongs survival time in endotoxic shock.

PMID- 21190603
TI  - [Effect of total saponins of Panax notoginseng on urinary albumin in patients
      with chronic renal failure].
AB  - OBJECTIVE: To observe the curative effect of total saponins of Panax notoginseng
      (PNS) on chronic renal failure (CRF). METHODS: Sixty patients with CRF (non
      uremic) were randomly divided into the experimental and the control groups, with
      30 cases in each group. Patients in experimental group were given PNS extract
      Xueshuantong 0.45 g on the basis of the general symptomatic treatment, once a
      day. While the patients in the control group were treated with Bailing capsule of
      1.0 g, three times a day. Total therapeutic courses were 2 months for both
      groups. The changes in renal function, hemoglobin, 24-hour urinary protein,
      parathyroid hormone (PTH), N-acutely-beta-D-glucosaminidase (NAG) were observed
      in two groups. RESULTS: After 2 months, the changes in serum creatinine (SCr),
      clearance rate of endogenous creatinine (CCr), blood urea nitrogen (BUN), uric
      acid (UA), hemoglobin, 24-hour urinary protein were improved in both groups,
      while the changes in CCr, BUN, hemoglobin, 24-hour urinary protein in the
      experimental group were more obvious [CCr (ml/s): 0.36+/-0.13 vs. 0.34+/-0.12,
      BUN (mmol/L): 15.66+/-9.05 vs. 20.32+/-8.30, hemoglobin (g/L): 101.2+/-9.4 vs.
      95.4+/-8.7, 24-hour urinary protein (mg): 1 040+/-450 vs. 2 360+/-390, all
      P<0.05]. After treatment, NAG (U/L) were decreased significantly only in control
      group (18.2+/-9.8 vs. 28.9+/-12.0, P<0.05). CONCLUSION: PNS has a good
      therapeutic effect for the treatment of CRF (non-uremic). It possesses such
      therapeutic effects as improving the renal function, and lowering urine protein.

PMID- 21190604
TI  - [The effect of Janus kinase 2 inhibitor AG490 on renal tubular epithelial
      myofibroblast transdifferentiation induced by interleukin-1beta].
AB  - OBJECTIVE: To investigate the effect of AG490, a Janus kinase 2 inhibitor, on
      epithelial-myofibroblast transdifferentiation induced by interleukin-1beta (IL
      1beta). METHODS: Cultured human renal tubular epithelial cell line (HKCs) were
      divided into three groups: blank control group, IL-1beta (5 ng/ml) group and
      AG490 group (IL-1beta 5 ng/ml+AG490 10 MUmol/L). The cells in all groups were
      collected at 24, 48, 72 hours after intervention. Immunocytochemistry and Western
      blotting analysis were used to determine the expressions of cytokeratin-18 (CK
      18) and alpha-smooth muscle actin (alpha-SMA). RESULTS: The higher expression of
      CK-18 (1.25+/-0.08) and mild expression of alpha-SMA (0.17+/-0.01) were found in
      blank control group. In IL-1beta group, the protein level of CK-18 was gradually
      decreased with prolongation of stimulus (24 hours : 0.69+/-0.04, 48 hours: 0.52+/
      0.03, 72 hours: 0.30+/-0.01), while the expression level of alpha-SMA was
      gradually increased (24 hours: 0.56+/-0.04, 48 hours: 1.05+/-0.07, 72 hours:
      1.43+/-0.07), and the difference between blank control group and IL-1beta group
      was statistically significant (all P<0.05). The administration of AG490 could
      restore the expression of CK-18 (24 hours: 1.07+/-0.07, 48 hours: 0.93+/-0.06, 72
      hours: 0.83+/-0.06), and inhibit the expression of alpha-SMA induced by IL-1beta
      (24 hours: 0.33+/- 0.01, 48 hours: 0.52+/-0.01, 72 hours: 0.61+/-0.04). There was
      significant difference between AG490 group and IL-1beta group (all P<0.05). The
      results of immunocytochemistry and that of Western blotting were identical.
      CONCLUSION: IL-1beta can induce the transdifferentiation of renal tubular
      epithelial cells, up-regulate the expression of alpha-SMA, induce the renal
      tubular epithelial cells to transform to myofibroblast, while AG490 can inhibit
      the effect of IL-1beta.

PMID- 21190605
TI  - [Effect of ethyl pyruvate on expression of inflammatory factors and mitogen
      activated protein kinase proteins in renal ischemic/reperfusion injury in BABL/c
      mice].
AB  - OBJECTIVE: To investigate the effects of ethyl pyruvate (EP) on expression of
      proinflammatory related gene and proteins of mitogen-activated protein kinase
      (MAPK) in renal tissues in ischemic/reperfusion (I/R) injury in mice. METHODS:
      Fifty male BABL/c mice were randomly divided into sham operation group (n=8),
      model group (n=10), and EP treatment group (n=32). EP treatment group was
      subdivided into EP pretreatment group (administration of 40 mg/kg EP 30 minutes
      before reproduction of model, n=8), and 4, 6 and 12 hours treatment groups
      (administration of 40 mg/kg EP 4, 6 and 12 hours after reproduction of model,
      respectively, n=8 in each group). Bilateral renal artery was occluded with a
      microvascular clamp for 30 minutes to reproduce kidney I/R injury model, and the
      kidney was harvested at 24 hours after I/R. The mRNA expressions of interleukins
      (IL-1beta, IL-6), tumor necrosis factor-alpha (TNF-alpha), intercellular adhesion
      molecule-1 (ICAM-1) and high-mobility group box 1 (HMGB1) were determined by real
      time reverse transcription-polymerase chain reaction (RT-PCR). The changes in
      protein levels of MAPKs [extracellular regulated protein kinase 1/2 (ERK1/2), c
      Jun N-terminal kinase (JNK), p38MAPK] were determined by Western blotting
      analysis. RESULTS: Real-time PCR assay showed that the mRNA expressions of IL
      1beta, IL-6, TNF-alpha, ICAM-1, HMGB1 in renal tissue were much higher than those
      in sham operation group (IL-1beta: 12.05+/-8.08 vs. 3.18+/-1.13, IL-6: 10.26+/
      6.85 vs. 0.81+/-0.34, TNF-alpha: 5.83+/-3.85 vs. 0.67+/-0.34, ICAM-1: 3.87+/-2.02
      vs. 0.29+/-0.13, HMGB1: 652.82+/-78.50 vs. 112.31+/-32.50, all P<0.05); and the
      expression in EP treatment groups was markedly down-regulated than that in model
      group, especially in 12-hour treatment group (0.45+/-0.26, 0.66+/-0.13, 0.21+/
      0.11, 0.05+/-0.02, 212.26+/-3.20, respectively, all P<0.05). Western blotting
      analysis revealed that the expression of the phosphorylated forms of ERK1/2, JNK,
      p38MAPK proteins was significantly higher than in sham operation group (p-ERK1/2:
      1.13+/-0.38 vs. 0.48+/-0.34, p-JNK: 1.40+/-0.15 vs. 0.36+/-0.15, p-p38MAPK:
      0.47+/-0.15 vs. 0.21+/-0.17, all P<0.05); the expression of the phosphorylated
      forms of ERK1/2, JNK, p38MAPK in each EP treatment group was significantly down
      regulated compared with that in model group (all P<0.05). CONCLUSION: EP can
      effectively protect kidney from acute injury produced by I/R, which may be
      related to the regulation of proinflammatory genes and the MAPKs in renal tissue.

PMID- 21190607
TI  - [The change in serum level of procalcitonin in patients after liver
      transplantation].

PMID- 21190606
TI  - [The expression of suppressor of cytokine signaling-1/3 in renal tubular
      epithelial cells induced by high glucose].
AB  - OBJECTIVE: To observe the morphologic changes and the expression of suppressor of
      cytokine signaling-1/3 (SOCS-1/3) in renal tubular epithelial cells induced by
      high glucose (HG) and to investigate their significance. METHODS: The renal
      tubular epithelial cell line (HKCs) cultured in vitro were divided into blank
      control group, HG group, and Janus kinase 2 inhibitor AG490 group. HKC of blank
      control group was cultured for 8 hours in 5.5 mmol/L glucose, and the other two
      groups were cultured in 300.0 mmol/L glucose or 300.0 mmol/L glucose+10 MUmol/L
      AG490 for 2, 4, 6, 12, 24, 48 hours (n=6). The morphology and ultrastructure were
      observed with inversion microscope and electron microscope at different time
      points. Protein expression of SOCS-1/3 was assayed by immunocytochemistry and
      Western blotting; SOCS-1/3 mRNA was assessed by reverse transcription-polymerase
      chain reaction (RT-PCR). RESULTS: Under inversion microscope it was showed that
      12 hours after being cultured with HG, the cells assumed a spindle-shape, with
      irregular protrusions, and cellular membrane became indistinguishable with
      prolongation of time, with increase of intracellular granules. Under the electron
      microscope, it was seen that there was distinct decrease in microvilli on the
      cell membrane and mitochondria, with an increase in rough endoplasmic reticulum.
      The cellular changes were not obvious in AG490 group. Furthermore,
      immunocytochemistry and Western blotting showed that the immunoreactivity was
      localized in the cytoplasm as well as in the nuclei, and there was basic
      expression of SOCS-1/3 protein in normal HKC (0.218+/-0.023, 0.337+/-0.009). HG
      was shown to induce up-regulation of the expression of SOCS-1/3 protein at 4, 6,
      12, 24 hours compared with blank control group. The expression of SOCS-1 was
      highest at 4 hours (1.022+/-0.072), and that of SOCS-3 was highest at 6 hours
      (1.256+/-0.105, both P<0.01), while the expression of SOCS-1/3 protein in AG490
      group was lower than that in HG group (4 hours SOCS-1: 0.589+/-0.167, 6 hours
      SOCS-3 : 0.656+/-0.075, both P<0.05). However, HG induced a higher expression of
      SOCS-1/3 mRNA at 2, 4, 6, 12 hours compared with blank control group. The
      expression of SOCS-1 was highest at 4 hours (1.716+/-0.098 vs. 0.475+/-0.045,
      P<0.05), and that of SOCS-3 was highest at 6 hours (2.848+/-0.116 vs. 0.749+/
      0.086, P<0.01), while the expression of SOCS-1/3 mRNA in AG490 group was lower (4
      hours SOCS-1: 0.865+/-0.075, 6 hours SOCS-3: 0.923+/-0.116, both P<0.05).
      CONCLUSION: HG could produce morphology and ultrastructure changes in renal
      tubular epithelial cell, and it induces up-regulation of SOCS-1/3 expression.
      These changes might be related with negative regulation of Janus kinase
      (JAK)/signal transducers and activators of transcription (STAT)/SOCS pathway.

PMID- 21190608
TI  - [Treatment of 21 pelvic fracture patients in Qinghai Yushu earthquake].

PMID- 21190609
TI  - [Clinical analysis of hemodialysis combined with hemoperfusion for treatment in
      uremic patients].

PMID- 21190610
TI  - [Medical support of mass casualties in maritime disasters in peacetime].

PMID- 21190611
TI  - [Advancement of researches on biomarkers in acute kidney injury].

PMID- 21190612
TI  - [Study on the relation between anticancer drug-sensitivity and differentional
      expression of anticancer drug sensitivity related genes in non-small cell lung
      cancer cell lines].
AB  - BACKGROUND: In order to enhance the chemotherapeutic efficacy of advanced lung
      cancer and to practise the individualized treatment, it is necessary to find out
      the difference of anticancer drug-sensitivity in lung cancer cells. Comparing the
      array profile of related gene of anticancer drug-sensitivity between non-small
      cell lung cancer (NSCLC) cell lines and immortal human bronchial epithelial cell
      line BET2A, the difference of expression of related genes of anticancer drug
      sensitivity was detected. METHODS: With the technique of cDNA macroarray, the
      different related gene proceeding of anticancer drug sensitivity expression was
      analysed in 6 NSCLC cell lines and BET2A cell line. RT-PCR was used to reconfirm
      the results. RESULTS: Seventy-three genes which were differentially expressed
      were found from 1291 candidate genes, and there were 45 genes upregulated, and 28
      genes downregulated. The results of RT-PCR were consistent with those of cDNA
      macroarray. CONCLUSIONS: The main reason of different sensitivity might be the
      difference of related gene of anticancer drug sensitivity expression. The results
      of this study provide new targets for reversing multiple drug-resistance, and
      they also provide experimental evidence to develop some new drugs and to realize
      the individualized treatment clinically.

PMID- 21190613
TI  - [Experimental study of effects of retinoic acid on IL-1beta and IFN-gamma induced
      C3 and factor B secretion in lung cancer cell line].
AB  - BACKGROUND: It is urgently necessary to research an effective method to prevent
      and treat lung cancer since its incidence has increased sharply. The aim of this
      study is to investigate the regulated effects of retinoic acid (RA) on IL-1beta
      and IFN-gamma induced C3 and factor B secretion in human lung cancer cell line
      A549. METHODS: C3 and factor B in cultured medium were measured in lung cancer
      cell line A549 by ELISA and Western blot, and their cellular mRNA levels were
      measured by RT-PCR analysis. RESULTS: ELISA, Western blot and RT-PCR results
      showed that IL-1beta and IFN-gamma could significantly increase C3 and factor B
      secretion and their mRNA levels in A549 cells. RA alone did not affect C3 and
      factor B level in A549 cells, but it could potentiated C3 and factor B secretion
      and their mRNA expression induced by IL-1beta, as well as factor B secretion and
      its mRNA expression induced by IFN-gamma. CONCLUSIONS: RA can up-regulate C3 and
      factor B secretion induced by IL-1beta and IFN-gamma in human lung cancer cell
      A549. It may stabilize the balance between stimulator cytokines and inhibitor
      cytokines in complement system, and play a certain role in killing tumor cells.
      The results suggest that combination of RA and cytokines might be effective in
      the treatment of lung cancer.

PMID- 21190614
TI  - [Effect of inhibitor kappaB transfection on tumorigenesis of human lung cancer
      cell line H460].
AB  - BACKGROUND: Nuclear factor kappaB (NFkappaB) is involved in oncogenesis and
      development. Inhibiting its activity may affect cancer cell growth. The aim of
      this study is to investigate the effects of inhibitor kappaB transfection on
      proliferation and tumorigenesis of human lung cancer cell line H460. METHODS:
      H460 cells were transfected with adenovirus expressing inhibitor kappaBalpha or
      LacZ (AdIkappaBalpha/AdLacZ) and cell viability was detected. Apoptosis was
      detected by Annexin-V/PI stain and caspase 3 activity measurement. In (vivo)
      tumorigenesis test was performed in nude mice inoculated with transfected H460
      cells. The therapeutic effect of AdIkappaBalpha was evaluated in the inoculated
      tumors. p65, p53 and VEGF expressions were detected in implanted tumor tissues by
      immunohistochemical stain. RESULTS: AdIkappaBalpha transfection significantly
      inhibited the proliferation of H460 cells. Apoptosis and expression level of
      caspase 3 in 30 MOI AdIkappaBalpha transfection group were remarkably higher than
      those in control groups (P < 0.05). In vivo study showed tumor incidence was
      significantly lower in 30 MOI AdIkappaBalpha transfection group than that in
      virus control group (P=0.012). For established H460 tumors, intratumoral
      injection of AdIkappaBalpha could significantly inhibit the tumor growth.
      Immunohistochemical stain showed VEGF expression was decreased in 30 MOI
      AdIkappaBalpha transfection group and p65 activity was blocked in H460 cells by
      AdIkappaBalpha transfection. CONCLUSIONS: AdIkappaBalpha transfection can inhibit
      the growth of H460 cells, as well as tumorigenesis. It might be due to both
      blockade of NFkappaB activity and inhibition of VEGF expression, which would be
      independent of p53 expression.

PMID- 21190615
TI  - [Antiangiogenic effect of continuous low-dose chemotherapy on Lewis lung
      carcinoma].
AB  - BACKGROUND: Recently a number of preclinical studies have sparked interest in the
      concept of exploiting conventional chemotherapeutic drugs as antiangiogenics.
      Such antiangiogenic activity is achieved by metronomic-dosing (low-dose)
      protocols. This new target may have some advantages in avoiding toxicity and
      resistance caused by chemotherapeutic drugs. This study is to test the efficacy
      of continuous low-dose cyclophosphamide (CTX) for antiangiogenic effect on Lewis
      lung carcinoma, and investigate its antitumor effect and toxicity. METHODS:
      C57/BL6 mice bearing Lewis lung carcinoma were randomly divided into three
      groups, receiving low-dose metronomic (LDM) CTX, maximum tolerated dose (MTD) CTX
      therapy and saline respectively. Tumor growth, weight loss, peripheral white
      blood cell counts and survival of mice were monitored in each group. At the end
      of experiment, tumors were resected for immunohistochemical staining. Tumor
      microvascular density (MVD) and vascular endothelial growth factor (VEGF) level
      were detected by immunohistochemical staining. RESULTS: MVD and VEGF expression
      of tumors were much lower in the mice received LDM CTX therapy than those in
      control group and MTD CTX group (P < 0.05). During the experiment, growth delays
      of tumor were found in the mice received LDM CTX therapy, without apparent body
      weight loss or leukopenia, and the survival of mice was remarkably prolonged,
      compared with mice received MTD CTX therapy (P < 0.05). CONCLUSIONS: The
      continuous low-dose regimen of CTX can significantly increase the therapeutic
      activity with decreased toxicity and prolonged animal survival for lung cancer.
      It may act as an antiangiogenic and lead to less drug resistance.

PMID- 21190616
TI  - [A rapid and simple method for extracting mitochondrial DNA from human lung
      cancer tissue].
AB  - BACKGROUND: The relationship between mitochondrial DNA (mtDNA) mutation and tumor
      is the hot point in cancer research field by now. The existent methods for
      extracting mtDNA are time-consuming and complicated. In order to further research
      the relationship of the mutation of mtDNA and development of lung cancer, it is
      necessary to establish a rapid and simple method for extracting mtDNA from lung
      cancer tissue. METHODS: Lung cancer tissues were lysed in base-denaturalization
      liquid and mtDNA was directly extracted from them by chloroform:isoamyl alcohol
      (24:1). The mtDNA was confirmed by PCR. RESULTS: The extracted mtDNA samples were
      not combinated with protein and 1528bp PCR products of (mtDNA) were detected from
      40 samples of analyzing patients. About (7.97+/-0.12)MUg of mtDNA could be
      extracted from 1 gram of cancer tissue. CONCLUSIONS: The method is simple, rapid
      and efficient to extract (mtDNA) from human lung cancer tissues and it could be
      used to handle small amount tissues or large number of samples in clinical and
      scientific research.

PMID- 21190617
TI  - [Expression of KAI1 gene in non-small cell lung cancer and its relationship with
      P53].
AB  - BACKGROUND: Recent researches have manifested that down-regulation of KAI1
      relates to metastasis in various tumors, but its association with non-small cell
      lung cancer (NSCLC) and the mechanism for its down-regulation are not clear. The
      aim of this study is to investigate the expression of KAI1 in NSCLC and its
      relationship with clinicopathological characteristics and mutant P53 protein.
      METHODS: The expression of KAI1/CD82 and mutant P53 protein was detected in 48
      cases of NSCLC tissues by Western blot, and KAI1 mRNA was detected by RT-PCR
      method, with 20 cases of pulmonary benign disease tissues and normal lung tissues
      as control.. RESULTS: The positive rate of KAI1 mRNA was 52% in lung cancer group
      and 90% in control group, respectively (P < 0.01), KAI1/CD82 was 48% and 85%
      respectively (P < 0.01), and mutant P53 protein was 65% and 5% respectively (P <
      0.01). The positive rate of KAI1 mRNA, KAI1/CD82 and mutant P53 protein closely
      related to the tumor stages, cell differentiation and lymph node metastasis
      status (P < 0.05 or P < 0.01). The expression of KAI1/CD82 highly related to KAI1
      mRNA (P < 0.01) and mutant P53 protein (P < 0.05), while expression of KAI1 mRNA
      did not relate to mutant P53 protein expression (P > 0.05). CONCLUSIONS: The down
      regulation of KAI1 may relate to carcinogenesis, development and metastasis of
      NSCLC. Its reduction may occur mainly at transcriptional level and correlate with
      p53 in NSCLC. KAI1 and p53 might be helpful to predict the potential metastasis
      of NSCLC.

PMID- 21190618
TI  - [Clinical value of capture of cancer cells in pleural fluid of patients with lung
      cancer by cytochip].
AB  - BACKGROUND: Immunocytochemistry is valuabale in differentiating malignant fluids
      from benign ones. However, the diagnostic value of a single tumor marker is
      limited. The aim of this study is to evaluate the clinical value of capture of
      cancer cells in pleural fluids of patients with lung cancer by cytochip. METHODS:
      A new pattern cytochip was developed to immunize hybridization of cells in
      pleural fluids of patients with 42 lung cancers and with 20 lung benign lesions.
      Ten antibodies were fixed on the cytochip, they were epithelial specific antigen
      (ESA), CD44V6, ND-1, T cell (CD3), CD45RO, B cell (CD20), CD79a, Hodgkin's cell
      (CD15), CD30 and macrophage (CD68). RESULTS: The point of positive hybridization
      showed round distribution with clear border, and the shape of cell displayed
      well. The positive numbers of ESA, CD44V6, ND-1 were 35, 30, 38 respectively in
      pleural fluids of 42 patients with luog cancers; lymphocytes and neutrophils were
      found on the 1 ESA and 1 ND-1 respectively, and only lymphocytes were found on
      the 3 CD44V6 in 20 ones with lung benign lesions; the other 7 antibodies did not
      capture cancer cells except for lymphocytes, neutrophils and macrophages from two
      pleural fluids. CONCLUSIONS: The cytochip could be an important practical
      foreground in clinic for diagnosing cancer cells in pleural fluids of patients
      with lung cancer.

PMID- 21190619
TI  - [Transcription expression of endostatin mRNA in non-small cell lung cancer
      tissues].
AB  - BACKGROUND: It has been proved that tumor development and metastasis are
      dependent on angiogenesis. Suppression of tumor angiogenesis can inhibit tumor
      growth and metastasis. Collagen X VIII/endostatin is one of the most effective
      inhibitors of angiogenesis at present. The aim of this study is to study the
      relationship between transcription expression of endostatin mRNA and clinical and
      pathophysiological characteristics in non-small cell lung cancer (NSCLC).
      METHODS: The transcription expression of endostatin mRNA was detected in 46 lung
      cancer tissues and paracancerous lung tissues, 14 benign pulmonary lesion tissues
      as control by RT-PCR method. RESULTS: (1)The transcription expression of
      endostatin mRNA in lung cancer tissues (0.872+/-0.071) was significantly higher
      than that in paracancerous tissues (0.717+/-0.073) and benign pulmonary lesion
      tissues (0.611+/-0.026) (P < 0.001).(2)The transcription expression of endostatin
      mRNA in lung cancer tissues was closely related to P-TNM stages, distant
      metastasis, grade of cell differentiation and size of the primary tumors (P <
      0.05), but not to location of tumor, lymph node status, histological
      classification, age and sex of the patients and smoking or not (P > 0.05).
      CONCLUSIONS: The transcription expression of endostatin mRNA in NSCLC tissues is
      significantly higher than that in paracancerous tissues and benign pulmonary
      lesion tissues, and is closely related to P-TNM stages, distant metastasis, grade
      of cell differentiation and size of the primary tumors, hence it might be helpful
      to evaluate the biological behavior of lung cancer.

PMID- 21190620
TI  - [Expression of E-cadherin and beta-catenin and their significance in non-small
      cell lung cancer].
AB  - BACKGROUND: Because invasion and metastasis of cancer threaten seriously human's
      life, it is of more important clinical significance to understand and evaluate
      the biologic behavior of can-(cer) correctly. Abnormal expression of E-cadherin
      and beta-catenin plays important roles in invasion and metastasis of cancer. The
      objective of this study is to investigate their expression in non-small cell lung
      cancer (NSCLC) and to find out their correlation with histological type, cell
      differentiation, metastasis and prognosis of NSCLC. METHODS: The expression of E
      cadherin and beta-catenin was detected in 129 NSCLC tissues by high sensitive S-P
      immunohistochemical method. RESULTS: The abnormal expression rate of E-cadherin
      and beta-catenin was 62.0% and 65.1% respectively. The abnormal expression rate
      of E-cadherin in squamous cell carcinoma was much higher than that in
      adenocarcinoma (P < 0.05). The abnormal expression rate of E-cadherin and beta
      catenin in poorly differentiated cells was significantly higher than that in well
      and moderately differentiated cells (P < 0.05, P < 0.05). Stage III/IV NSCLC
      showed markedly higher abnormal expression rate of E-cadherin and beta-catenin
      than stage I/II NSCLC did (P < 0.01, P < 0.01). The abnormal expression rate of E
      cadherin and beta-catenin in patients with lymphatic metastasis was significantly
      higher than that in those without lymphatic metastasis (P < 0.05, P < 0.01). The
      mean survival duration and 5-year survival rate in patients with normal E
      cadherin and beta-catenin expression were remarkably higher than those in
      patients with abnormal expression (P < 0.05, P < 0.01). CONCLUSIONS: The abnormal
      expression of E-cadherin and beta-catenin is closely related to histological
      type, differentiation and metastasis in NSCLC. Detection of their expression
      might be helpful to predict prognosis of NSCLC.

PMID- 21190621
TI  - [Study on the expression and their relationship among P27, Bcl-2 and VEGF in lung
      cancer].
AB  - BACKGROUND: The occurrence of cancer needs many kinds of oncogenes and their
      cooperation, such as Bcl-2, p27, and vascular endothelial growth factor (VEGF)
      etc. They have different contributions in lung cancer's occurrence and
      development by different paths. In this study the expression of P27, Bcl-2, VEGF
      and their relationship in lung cancer were investigated. METHODS: The expression
      of P27, Bcl-2 and VEGF was detected in 85 lung cancer and 21 benign pulmonary
      tissues by the immunohistochemistry staining. RESULTS: Positive rate of VEGF and
      Bcl-2 protein expression was 65.88% (56/85) and 61.18% (52/85) respectively in
      lung cancer tissue, which was higher than that in benign pulmonary tissues
      (14.29% and (19.05%)) (P < 0.05). Positive rate of P27 protein expression in lung
      cancer tissue (37.65%, 32/85) was significantly lower than that in benign
      pulmonary tissues (80.95%, 17/21) (P < 0.05). VEGF expression was closely related
      to the grade of cell differentiation, P-TNM stage and lymph node status; Bcl-2
      expression was closely related to histology of lung cancer, P-TNM stage and grade
      of cell differentiation; and P27 expression was closely related to grade of cell
      differentiation. There was correlation between P27 and Bcl-2 and between P27 and
      VEGF protein, but no correlation between Bcl-2 and VEGF. CONCLUSIONS: Detection
      of P27, Bcl-2 and VEGF will be valuable for dignosing lung cancer and evaluating
      malignancy extent.

PMID- 21190622
TI  - [Analysis of the relationship between polymorphism of angiotensin-converting
      enzyme gene and lung cancer].
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE), the key enzyme of RAS, is
      expressed in abundance in lung. Recent studies show that it plays various
      biological roles and even contributes importantly to the carcinogenesis of
      malignant tumors. The aim of this study is to investigate whether the insertion
      (I)/deletion (D) polymorphism of ACE is related to the susceptibility,
      pathological type or staging of lung cancer. METHODS: DNA was extracted from the
      peripheral veinous blood derived from 47 lung cancer patients and 54 normal
      persons. The ACE genotype of each sample was amplified with PCR. RESULTS: The
      frequencies of II, ID and DD genotype of ACE in lung cancer group were 0.447,
      0.447 and 0.106 respectively, and the frequencies of I and D allele were 0.670
      and 0.330 respectively. The frequencies of II, ID and DD geno-(type) of ACE in
      control group were 0.370, 0.556 and 0.074 respectively, and the frequencies of I
      and D allele were 0.648 and 0.352 respectively. There was no significant
      difference of ACE genotypes or alleles frequencies between the lung cancer and
      control groups. No significant difference of ACE genotypes or alleles frequencies
      was found between small cell lung cancer and non-small cell lung cancer groups or
      between the different staging groups of lung cancer patients. CONCLUSIONS: No
      association is found between the polymorphism of ACE gene and the susceptibility,
      pathological type or clinical staging of lung cancer.

PMID- 21190623
TI  - [Expression of CD44v6 and its prognostic significance in non-small cell lung
      cancer].
AB  - BACKGROUND: Overexpression of CD44v6 is associated with occurrence, development
      and metastasis of a variety of human malignant tumors. The aim of this study is
      to determine the expression of CD44v6 and its prognostic significance in non
      small cell lung cancer (NSCLC). METHODS: CD44v6 expression was detected in 52
      NSCLC tissues and 12 normal pulmonary tissues by reverse transcription polyme
      (rase) chain reaction (RT-PCR) and immunohistochemistry (SP method). RESULTS: The
      positive expression rate of CD44v6 was 69.2% (SP method) and 75.0% (RT-PCR
      method) in NSCLC, respectively. Significantly higher expression of CD44v6 was
      demonstrated in poorly differentiated tumors than that in moderately/well
      differentiated tumors (P < 0.05). The expression of CD44v6 was remarkably higher
      in patients with lymphatic metastasis than that in those without lymphatic
      metastasis (P < 0.01). CD44v6 expression in stage III NSCLC was remarkably higher
      than that in stage I and II NSCLC (P < 0.05). Survival rate of patients with
      negative CD44v6 expression was significantly higher than that of those with
      positive CD44v6 expression (P=(0.0115)). Multi-variate logistic analysis showed
      the expression of CD44v6 (P=0.048) and pTNM stage (P=0.035) were significantly
      prognostic factors. CONCLUSIONS: Overexpression of CD44v6 is very common in lung
      cancer tissues. Detection of CD44v6 expression may be helpful to predict the
      prognosis of NSCLC patients.

PMID- 21190624
TI  - [Detection of occult micrometastasis using MAGE genes in lymph nodes of patients
      with non-small cell lung cancer].
AB  - BACKGROUND: Melanoma antigen genes (MAGE genes) are tumor specific genes. In this
      study the expressions of MAGE-1, -2, -3 and -4 genes in lymph nodes of patients
      with non-small cell lung cancer (NSCLC) at mRNA level were investigated and the
      role of MAGE genes was analyzed in the diagnosis of occult micrometastasis in
      lymph nodes of patients with NSCLC. METHODS: One hundred and eleven stations of
      lymph nodes from 53 patients with NSCLC were studied to detect mRNA for MAGE-1, 
      2, -3 and -4 genes by using reverse transcription-polymerase chain reaction (RT
      PCR) assay. RESULTS: The expression rate in samples of lymph nodes using RT-PCR
      (41.4%, 46/111) was significantly higher than that using routine
      histopathological examination (27.9%, 31/111). Of the 80 stations of lymph nodes
      without invasion of the tumor confirmed by routine histopathological examination,
      at least one of these genes was expressed in (23.8%) (19/80) out of the samples.
      Of the 31 stations of lymph nodes with invasion of the tumor confirmed by routine
      histopathological examination, at least one of these MAGE genes was expressed in
      87.1% (27/31) out of the samples. In the lymph nodes of the patients with non
      cancerous diseases, the MAGE-1, -2, -3 and -4 were not expressed at mRNA level.
      CONCLUSIONS: Micrometastasis in lymph nodes of patients with NSCLC could be
      diagnosed by investigating the expressions of MAGE genes at mRNA level. Detection
      of MAGE-1, (-2,) -3 and -4 might be helpful to diagnoze micrometastasis in lymph
      node and to increase the accuracy of TNM stages in NSCLC.

PMID- 21190625
TI  - [Combination of gemcitabine and cisplatin in the treatment of advanced non-small
      cell lung cancer].
AB  - BACKGROUND: The platinum-based combined chemotherapy is effective for advanced
      non-small cell lung cancer (NSCLC). This study is to observe the clinical effect
      and toxicity of combination of gemcitabine with cisplatin for advanced NSCLC.
      METHODS: All of 32 patients were pathologically confirmed as stage III or IV
      NSCLC who lost chance to receive operation. Gemcitabine was given on days 1, 8,
      15 at a dose of 1000mg/m2 and cisplatin on days 1-5 at a dose of 20mg. The
      chemotherapy was repeated every 28 days up to 3-4 cycles. RESULTS: There was no
      patient who got complete response, and the overall response rate was 34.4%
      (11/32). The median survival duration was 329 days and the 1-year survival rate
      was 32.7%. The main toxicities were myelosuppression, nausea and vomiting,
      however, there was no severe grade IV damage or obvious liver and kidney damage.
      No one was delayed for chemotherapy due to adverse effect. CONCLUSIONS: The
      combination of gemcitabine and cisplatin is effective and well tolerated in the
      treatment of advanced NSCLC.

PMID- 21190626
TI  - [Oxaliplatin combined with vinorelbine in the treatment of patients with advanced
      non-small cell lung cancer].
AB  - BACKGROUND: Vinorelbine (NVB) and oxaliplatin (OXA) have shown effective
      anticancer activity in a wide range of solid tumors. This study is to observe the
      efficacy and side effects of OXA in combination with NVB in the treatment of
      advanced non-small cell lung cancer (NSCLC). METHODS: Fifty-nine patients with
      NSCLC were randomly treated by OXA+NVB or cisplatin (DDP)+NVB regimen, repeated
      every 3-4 weeks. They received at least 2 cycles of chemotherapy. RESULTS: There
      were 29 patients treated with NO regimen, in which there was no complete response
      (CR) patient, 12 patients showed partial response (PR), and the response rate was
      41.4%. There were 30 patients treated with NP regimen. One patient showed CR, 13
      patients showed PR, and the response rate was 46.7%. There was no significant
      difference in response rate between the two groups (P > 0.05). The major
      toxicities, including leukopenia and phlebitis, were similar in the two groups.
      The incidences of gastrointestinal reaction and alopecia of NP regimen were more
      severe than those of NO regimen (P < 0.05), but neurotoxicity of NO regimen was
      more obvious than that of NP regimen (P < 0.05). CONCLUSIONS: The efficacy of the
      two regimens are similar in the treatment of advanced NSCLC. The side effects
      such as leukopenia and phlebitis are similar in the two groups. However, there
      are significant differences in gastrointestinal reaction, alopecia and
      neurotoxicity between the two groups. All the toxicities are well tolerable.

PMID- 21190627
TI  - [Efficacy of combined gemcitabine and cisplatin in the treatment of advanced non
      small cell lung cancer].
AB  - BACKGROUND: No chemotherapeutic regimen and agent are effective for most patients
      with advanced non-small cell lung cancer (NSCLC). This study is designed to
      evaluate the efficacy and toxicity of the combination of gemcitabine and
      cisplatin in the treatment of NSCLC.. METHODS: Sixty cases of NSCLC in stage III
      and IV were treated with gemcitabine 1200mg/m2 by intravenous infusion on 1st and
      8th days, and cisplatin 100mg/m2 by intravenous infusion on 1st day or 30mg/m2 by
      intravenous infusion on 1st and 8th days in a 28-day cycle. Each patient was
      treated at least for 2 cycles. RESULTS: An objective response was obtained in
      46.67% of patients (3 complete and 25 partial responses), whereas 22 patients had
      no change and 10 patients were progressive. The response rate was 57.14% in
      patients without prior chemotherapy and 22.22% in patients with prior treatment.
      Significant difference existed between the two groups (P < 0.05). The main
      toxicities were leukopenia and thrombocytopenia, but didn't influence the
      chemotherapy. CONCLUSIONS: The combination of gemcitabine and cisplatin is a
      feasible, well-tolerated and effective scheme in the treatment of advanced NSCLC.

PMID- 21190628
TI  - [Informed consents and impact in the medical research].

PMID- 21190629
TI  - [Clinical characteristics and tilt test of patients with vasovagal syncope
      suspicion].
AB  - BACKGROUND: Vasovagal syncope is the most common cause of syncope and is an
      amount medical, social and economic problem. MATERIAL AND METHODS: We study a
      population of patients with history of syncope of presumed vasovagal origin
      submitted to head-up tilt test (TT) with intention to describe and to compare
      symptoms, signs and trigger situations between positive and negative TT. Twenty
      four variables were investigated (chosen according to the clinical experience).
      RESULTS: One hundred thirteen patients were included. The age mean was 33,3 +/-
      19,4 years and 67.3% corresponded to women. 81 patients (71,7%) experienced
      syncope during test. The more frequent response was mixed subtype (58 %),
      followed by vasodepressor response (30,9%) and cardioinhibitory response (11,1%).
      There were not significant differences between both groups in symptoms, signs and
      trigger situations. In patients with negative TT was more frequent syncopes
      triggered by extreme exercise (p = 0,012). CONCLUSION: In patients with vasovagal
      syncope suspicion, a clinic history does not predict TT results.

PMID- 21190630
TI  - [The importance of laboratory in the diagnosis in Sjogren's syndrome].

PMID- 21190631
TI  - [Insipid diabetes as initial presentation of Wegener's granulomatosis].
AB  - Wegener's granulomatosis is a granulomatous necrotizing vasculitis which
      predominantly affects the respiratory tract, kidney, and less frequently other
      organs such as the nervous system. The latter may occur in up to 54% of cases and
      when it does it is more frequently of the peripheral nerves. We present a 19 year
      old woman who commenced her disease with involvement of respiratory sinuses,
      lungs and kidney and who developed central insipid diabetes (CID) at onset. The
      CID persisted in spite of adequate response of the other organs and systems with
      immunosuppresor treatment. The development of CID in the context of vasculitis
      should suggest this as a possible mechanism.

PMID- 21190632
TI  - [Dysnatremia].

PMID- 21190633
TI  - The differential diagnosis of schizoaffective disorder.
AB  - Correctly diagnosing schizoaffective disorder depends on eliciting and
      documenting an accurate history of the patient's signs and symptoms, including
      the duration, intensity, and time course. To assist in making the differential
      diagnosis of schizoaffective disorder, clinicians should carefully gather
      information from patients and other informants, consider the information within a
      conceptual diagnostic framework, differentiate between schizoaffective disorder
      and other disorders, and re-evaluate the diagnosis over time.

PMID- 21190634
TI  - Pharmacologic therapy for fibromyalgia.
AB  - While nonpharmacologic strategies can help patients understand and accept the
      diagnosis of fibromyalgia, pharmacologic therapy can provide important additional
      symptom relief and improvement in functioning. Pharmacologic therapy must be
      individualized based on a comprehensive evaluation of the patient and continued
      assessment of symptoms and response to treatment. Patient symptoms and
      impairments related to each of the dimensions of the "fibromyalgia triad" (pain,
      sleep dysfunction, and mood disorders) as well as any other comorbidities, past
      experiences with treatment, and patient preferences should guide therapy
      selection.

PMID- 21190635
TI  - Approaches to preventing relapse in bipolar disorder: addressing nonadherence and
      prodromal symptoms.
AB  - The goals of maintenance treatment for euthymic patients with bipolar disorder
      are to prevent recurrence of acute episodes and to optimize the patient's
      adaptive functioning. Although medications are the primary treatment for
      preventing relapse, patient outcomes can be enhanced through the use of
      psychosocial interventions that address barriers to treatment success such as
      nonadherence to medication and lack of patient or caregiver understanding of the
      illness. Patients can learn to take an active and responsible role in managing
      their illness, including monitoring their symptoms to recognize prodromal signs
      of relapse, protecting daily social rhythms and routines, and maintaining healthy
      activities.

PMID- 21190636
TI  - Performance improvement CME: managing chronic pain.
AB  - Performance Improvement CME (PI CME) is an educational activity in which
      clinicians retrospectively assess their current clinical practice, choose areas
      for improvement and implement interventions based on treatment guidelines and
      health care standards, and then re-evaluate their clinical practice to assess the
      improvements made. This PI CME activity focuses on improving the safety and
      efficacy of treating chronic pain with opioid medications.

PMID- 21190637
TI  - Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for
      clinicians and a reconsideration of mechanisms.
AB  - BACKGROUND: It is generally believed that selective serotonin reuptake inhibitor
      (SSRI) drugs increase the risk of abnormal bleeding and decrease the risk of
      ischemic heart disease events by blocking the uptake of serotonin into platelets,
      leading to an impairment in the platelet hemostatic response. OBJECTIVE: To
      perform a detailed qualitative review of existing literature on the association
      of abnormal bleeding with the use of SSRIs. DATA SOURCES: We conducted a PubMed
      search during June 2009 using the search terms antidepressants and SSRIs
      (including the names of individual SSRIs: fluoxetine, sertraline, paroxetine,
      fluvoxamine, citalopram, and escitalopram) in association with bleeding,
      platelets, hemostasis, nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin,
      antiplatelet drugs, proton pump inhibitors, peptic ulcer, premenstrual dysphoric
      disorder, menstruation, pregnancy, postpartum hemorrhage, surgery, tooth
      extraction, dental bleeding, stroke, ischemic heart disease, and other terms
      related to the field. We then searched the reference lists of identified studies.
      STUDY SELECTION: We provide a qualitative discussion of all studies that would
      inform clinicians about the mechanisms of bleeding and bleeding risks associated
      with these drugs in different clinical contexts. RESULTS: Epidemiologic studies
      show that SSRI use is associated with roughly doubled odds of upper
      gastrointestinal (GI) bleeding; bleeding at other sites has been less commonly
      described, as has a possibly increased risk of bleeding associated with surgical
      procedures. The risk of SSRI-associated GI bleeding is increased with the
      concurrent use of NSAIDs, anticoagulants, and antiplatelet agents and is
      decreased by concurrent proton pump inhibitors. The risk of bleeding is increased
      in patients with cirrhosis of the liver or liver failure. There is, curiously,
      little literature on use of SSRIs and menstrual or postpartum blood loss.
      Selective serotonin reuptake inhibitors appear protective against ischemic heart
      disease events. The data are too limited to allow interpretations about
      influences on ischemic and hemorrhagic stroke. CONCLUSIONS: On the basis of the
      findings of our literature search, we suggest that SSRI-induced increase in
      gastric acid secretion may explain the GI bleeding risk and that SSRI-related
      effects on platelet reactivity, endothelial reactivity, and inflammatory markers
      may explain the ischemic heart disease protective effect. Because the absolute
      risk of GI bleeds with SSRIs is low, precautions are probably necessary only in
      high-risk patients, such as those with acid-peptic disease and those with a
      history of bleeds. We discuss management issues and areas for future research.

PMID- 21190638
TI  - The epidemiology of chronic major depressive disorder and dysthymic disorder:
      results from the National Epidemiologic Survey on Alcohol and Related Conditions.
AB  - OBJECTIVE: To examine the prevalence of chronic major depressive disorder (CMDD)
      and dysthymic disorder, their sociodemographic correlates, patterns of 12-month
      and lifetime psychiatric comorbidity, lifetime risk factors, psychosocial
      functioning, and mental health service utilization. METHOD: Face-to-face
      interviews were conducted in the 2001-2002 National Epidemiologic Survey on
      Alcohol and Related Conditions (n = 43,093). RESULTS: The 12-month and lifetime
      prevalences were greater for CMDD (1.5% and 3.1%, respectively) than for
      dysthymic disorder (0.5% and 0.9%, respectively). Individuals with CMDD and
      dysthymic disorder shared most sociodemographic correlates and lifetime risk
      factors for major depressive disorder. Individuals with CMDD and dysthymic
      disorder had almost identically high rates of Axis I and Axis II comorbid
      disorders. However, individuals with CMDD received higher rates of all treatment
      modalities than individuals with dysthymic disorder. CONCLUSIONS: Individuals
      with CMDD and dysthymic disorder share many sociodemographic correlates,
      comorbidity patterns, risk factors, and course. Individuals with chronic
      depressive disorders, especially those with dysthymic disorder, continue to face
      substantial unmet treatment needs.

PMID- 21190639
TI  - Suicidality is associated with medication access problems in publicly insured
      psychiatric patients.
AB  - BACKGROUND: Beginning January 1, 2006, the Medicare Part D prescription drug
      benefit shifted drug coverage from Medicaid to the new Medicare Part D program
      for patients who were eligible for both Medicare and Medicaid benefits ("dual
      eligibles"). These patients were randomly assigned to a private Part D plan and
      came under specific formulary and utilization management procedures of the plan
      in which they were enrolled. OBJECTIVE: To examine the relationship between
      physician-reported medication switches, discontinuations, and other access
      problems and suicidal ideation or behavior among "dual-eligible" psychiatric
      patients. METHOD: Data were collected in 3 cross-sectional cycles in 2006
      (January-April, May-August, and September-December) as part of the National Study
      of Medicaid and Medicare Psychopharmacologic Treatment Access and Continuity
      using through-the-mail, practice-based survey research methods. Data from the
      third cycle, representing all events since January 1, 2006, were used for these
      analyses. A national sample of psychiatrists randomly selected from the AMA
      Masterfile provided clinically detailed data on 1 systematically selected, dual
      eligible psychiatric patient (N = 908). Propensity score analyses adjusted for
      patient sociodemographics, treatment setting, diagnoses, and psychiatric symptom
      severity. RESULTS: Patients who experienced medication switches,
      discontinuations, and other access problems had 3 times the rate of suicidal
      ideation or behavior compared with patients with no access problems (22.0% vs
      7.4%, P < .0001). Mean odds ratios and excess probabilities were highest for
      patients who were clinically stable but were required to switch medications
      (31.8%; mean OR = 4.87, mean P = 8.92(-5), excess probability = 0.21). Patients
      who experienced discontinuations (26.4%; mean OR = 2.13, mean P = 2.12(-2),
      excess probability = 0.12), other access problems (18.7%; mean OR = 3.01, mean P
      = 1.03(-5), excess probability = 0.15), and multiple access problems (22.3%; mean
      OR = 2.88, mean P = 4.10(-5), excess probability = 0.14) also had significantly
      increased suicidal ideation or behavior. CONCLUSION: Increased occurrences of
      suicidal ideation or behavior appear to be associated with disruptions in patient
      medication access and continuity. Clinicians need to be aware of the possibility
      of increased suicidality when, for administrative reasons, a clinically stable
      patient's medication regimen is altered. Dual-eligible psychiatric patients
      represent a highly vulnerable group with a substantial burden of illness; these
      findings underscore the need to provide special protections for this population.

PMID- 21190641
TI  - Manic and psychotic symptoms following subcutaneous leuprolide in a male patient
      with no prior psychiatric history.

PMID- 21190640
TI  - Bipolar disorder: new perspectives in health care and prevention.
AB  - OBJECTIVE: High rates of misdiagnosis, delayed diagnosis, and lack of recognition
      and treatment of comorbid conditions often lead patients with bipolar illness to
      have a chronic course with high disability, unemployment rates, and mortality.
      Despite the recognition that long-term outcome of bipolar disorder depends on
      systematic assessment of both interepisodic dysfunctional domains and comorbid
      psychiatric and medical conditions, treatment of bipolar disorder still focuses
      primarily on alleviation of acute symptoms and prevention of future recurrences.
      We propose here to review the evidence offering a modern view of bipolar disorder
      defined as a chronic and progressive multisystem disorder, taking into account
      characteristics of each patient as well as biosignatures in order to help design
      personalized treatments. DATA SOURCES: We conducted a systematic PubMed search of
      all English-language articles, published between 2000 and 2010, focusing on the
      English and French literature with bipolar disorder cross-referenced with the
      following search terms: emotional dysregulation, sleep and circadian rhythm
      disturbances, cognitive impairment, age at onset, comorbid medical and
      psychiatric conditions, psychosocial and medical interventions, outcome,
      remission, and personalized medicine. The search was conducted between July 2009
      and July 2010. The literature on bipolar disorder was reviewed to provide
      supporting evidence that the assessment of various symptom domains that are
      dysfunctional between episodes should all be considered as core dimensions of the
      disorder. STUDY SELECTION: Forty-one articles were identified through the PubMed
      search described above and selected on the basis of addressing any combination of
      the search terms in conjunction with bipolar disorder. DATA SYNTHESIS: Current
      guidelines advocate the use of more or less similar treatment algorithms for all
      patients, ignoring the clinical, pathophysiological, and lifetime heterogeneity
      of bipolar disorder. Systematic assessment of interepisodic dimensions, along
      with comorbid medical and psychiatric risk factors, should be performed along the
      life cycle in order to plan specific and personalized pharmacologic, medical, and
      psychosocial interventions tailored to the needs of each patient and ready-to
      test biosignatures to serve as risk factors or diagnostic or prognostic tools.
      CONCLUSIONS: Medical and research findings, along with health economic data,
      support a more modern view of bipolar disorder as a chronic, progressive,
      multisystem disorder. This new comprehensive framework should guide the search to
      identify biomarkers and etiologic factors and should help design a new policy for
      health care, including prevention, diagnosis, treatment, and training.

PMID- 21190642
TI  - False-positive methadone drug screens during quetiapine treatment.

PMID- 21190643
TI  - Anticholinergic mechanisms: a forgotten cause of the switch process in bipolar
      disorder.

PMID- 21190645
TI  - Hospital personnel reactions to Haiti's earthquake: a preliminary matching study.

PMID- 21190646
TI  - Strategies for making an accurate differential diagnosis of schizoaffective
      disorder.
AB  - To make an accurate differential diagnosis of schizoaffective disorder,
      clinicians can carefully gather information from patients and other informants,
      consider the information within a conceptual diagnostic framework, differentiate
      between schizoaffective disorder and other disorders, and reevaluate the
      diagnosis over time. Making an accurate diagnosis of schizoaffective disorder can
      be difficult because patients may remember insufficient detail of symptoms
      including their duration and overlap. Clinicians should realize that the
      diagnostic stability and interrater reliability of schizoaffective disorder are
      low. An accurate history of patients' signs and symptoms and their course and
      duration is essential to making a diagnosis. Careful documentation of symptoms
      and recording of the basis for diagnosis are crucial so that the diagnosis can be
      reevaluated over time.

PMID- 21190647
TI  - Understanding schizoaffective disorder: from psychobiology to psychosocial
      functioning.
AB  - Psychobiologic evidence and psychosocial functioning in patients with
      schizoaffective disorder suggest that the disease may be a distinct disorder, a
      variant of schizophrenia or affective disorders, the comorbidity of schizophrenia
      and a mood disorder, or an intermediate disorder on a spectrum that ranges from
      schizophrenia to mood disorders. These data, although inconclusive, contribute to
      clinicians' understanding of the etiology of the disorder. Further research may
      lead to an increased understanding of the disorder, improved treatment, and,
      ultimately, better outcomes.

PMID- 21190648
TI  - Developing an individualized treatment plan for patients with schizoaffective
      disorder: from pharmacotherapy to psychoeducation.
AB  - To develop an individualized treatment plan that addresses both psychotic and
      affective symptoms in patients with schizoaffective disorder, clinicians can take
      several steps. First, clinicians can confirm the diagnosis. In the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)
      and in the International Classification of Diseases, Tenth Revision (ICD-10),
      schizoaffective disorder is defined differently, but, diagnostically, the
      disorder falls on a spectrum between bipolar disorder and schizophrenia and can
      be divided into bipolar and depressive types. Next, clinicians can evaluate
      predictors of outcome. Outcomes can be predicted by previous functioning, number
      of previous episodes, persistence of psychotic symptoms, and level of cognitive
      impairment. Then, clinicians can use evidence from clinical trials to guide
      selection of acute and maintenance phase treatment. Although data are limited,
      direct and indirect evidence from clinical trials support pharmacologic and
      psychoeducational interventions. In bipolar type schizoaffective disorder,
      evidence supports the use of an atypical antipsychotic and a mood stabilizer or
      atypical antipsychotic monotherapy. In the depressive type of the disorder, the
      combination of an atypical antipsychotic and an antidepressant is probably the
      best choice, but an atypical antipsychotic and a mood stabilizer could also be
      used. In both types of the disorder, patient psychoeducation can be beneficial in
      the maintenance phase of treatment. Adherence to treatment is essential for
      optimal outcome, and, besides patient psychoeducation, long-acting injectable
      antipsychotics and psychoeducation for caregivers may also improve adherence. In
      refractory cases, electroconvulsive therapy is an option.

PMID- 21190649
TI  - Strategies for improving treatment adherence in schizophrenia and schizoaffective
      disorder.
AB  - Nonadherence with medication treatment is common but difficult to detect in
      patients with schizoaffective disorder and schizophrenia, almost half of whom
      take less than 70% of prescribed doses. Like patients in all areas of medicine,
      patients with schizoaffective disorder weigh the perceived benefits of
      medications against perceived disadvantages, but this process is complicated by
      their impaired insight, the stigma of the diagnosis, and the often troubling side
      effects of antipsychotic medication. Interventions to improve adherence include
      encouraging acceptance of the illness, drawing analogies with treatment for
      chronic medical disease, and involving the patient in decision making. Clinicians
      must remain nonjudgmental, encouraging patients to disclose problems with
      adherence and anticipating that improvement in adherence may require a prolonged
      effort. Selection of antipsychotic medication is critical to avoid adverse side
      effects, and some medications may provide a sense of well-being, such as
      improvement in insomnia, anxiety, or depression. Depot (rather than oral)
      antipsychotics can improve adherence and provide the clinician with reliable
      information about the dosage of medication received, which can be used for
      purposes of dose adjustments or to guide response to relapse.

PMID- 21190650
TI  - Asymmetric GUVs prepared by MbetaCD-mediated lipid exchange: an FCS study.
AB  - We report a simple method to obtain stable asymmetric giant unilamellar vesicles
      (GUVs). Fluorescence correlation spectroscopy was used to quantitatively
      characterize vesicle properties. After brain sphingomyelin (bSM) was exchanged
      into dioleoylphosphatidylcholine (DOPC) GUVs, lateral diffusion in the bSM
      containing outer leaflet decreased, whereas that in the DOPC-containing inner
      leaflet was largely unchanged, confirming asymmetry and a lack of coupling
      between the physical states of the inner and outer leaflets. In contrast, after
      bSM was exchanged into brain phosphatidylcholine vesicles, lateral diffusion
      decreased in both leaflets. Thus, asymmetric GUVs should be useful for
      investigating the molecular mechanisms behind interleaflet coupling.

PMID- 21190651
TI  - Feed-forward and feed-backward amplification model from cochlear
      cytoarchitecture: an interspecies comparison.
AB  - The high sensitivity and wide bandwidth of mammalian hearing are thought to
      derive from an active process involving the somatic and hair-bundle motility of
      the thousands of outer hair cells uniquely found in mammalian cochleae. To better
      understand this, a biophysical three-dimensional cochlear fluid model was
      developed for gerbil, chinchilla, cat, and human, featuring an active "push-pull"
      cochlear amplifier mechanism based on the cytoarchitecture of the organ of Corti
      and using the time-averaged Lagrangian method. Cochlear responses are simulated
      and compared with in vivo physiological measurements for the basilar membrane
      (BM) velocity, V(BM), frequency tuning of the BM vibration, and Q10 values
      representing the sharpness of the cochlear tuning curves. The V(BM) simulation
      results for gerbil and chinchilla are consistent with in vivo cochlea
      measurements. Simulated mechanical tuning curves based on maintaining a constant
      V(BM) value agree with neural-tuning threshold measurements better than those
      based on a constant displacement value, which implies that the inner hair cells
      are more sensitive to V(BM) than to BM displacement. The Q10 values of the V(BM)
      tuning curve agree well with those of cochlear neurons across species, and appear
      to be related in part to the width of the basilar membrane.

PMID- 21190652
TI  - A model of the interaction between N-type and C-type inactivation in Kv1.4
      channels.
AB  - Kv1.4 channels are Shaker-related voltage-gated potassium channels with two
      distinct inactivation mechanisms. Fast N-type inactivation operates by a ball-and
      chain mechanism. Slower C-type inactivation is not so well defined, but involves
      intracellular and extracellular conformational changes of the channel. We studied
      the interaction between inactivation mechanisms using two-electrode voltage-clamp
      of Kv1.4 and Kv1.4DeltaN (amino acids 2-146 deleted to remove N-type
      inactivation) heterologously expressed in Xenopus oocytes. We manipulated C-type
      inactivation by introducing a lysine-tyrosine point mutation (K532Y, equivalent
      to Shaker T449Y) that diminishes C-type inactivation. We used experimental data
      to develop a comprehensive computer model of Kv1.4 channels to determine the
      interaction between activation and N- and C-type inactivation mechanisms needed
      to replicate the experimental data. C-type inactivation began at lower voltage
      preactivated states, whereas N-type inactivation was coupled directly to the open
      state. A model with distinct N- and C-type inactivated states was not able to
      reproduce experimental data, and direct transitions between N- and C-type
      inactivated states were required, i.e., there is coupling between N- and C-type
      inactivated states. C-type inactivation is the rate-limiting step determining
      recovery from inactivation, so understanding C-type inactivation, and how it is
      coupled to N-type inactivation, is critical in understanding how channels act to
      repetitive stimulation.

PMID- 21190653
TI  - Protein diffusion in the periplasm of E. coli under osmotic stress.
AB  - The physical and mechanical properties of the cell envelope of Escherichia coli
      are poorly understood. We use fluorescence recovery after photobleaching to
      measure diffusion of periplasmic green fluorescent protein and probe the fluidity
      of the periplasm as a function of external osmotic conditions. For cells adapted
      to growth in complete medium at 0.14-1.02 Osm, the mean diffusion coefficient
      <D(peri)> increases from 3.4 MUm2 s-1 to 6.6 MUm2 s-1 and the distribution of
      D(peri) broadens as growth osmolality increases. This is consistent with a net
      gain of water by the periplasm, decreasing its biopolymer volume fraction. This
      supports a model in which the turgor pressure drops primarily across the thin
      peptidoglycan layer while the cell actively maintains osmotic balance between
      periplasm and cytoplasm, thus avoiding a substantial pressure differential across
      the cytoplasmic membrane. After sudden hyperosmotic shock (plasmolysis), the
      cytoplasm loses water as the periplasm gains water. Accordingly, <D(peri)>
      increases threefold. The fluorescence recovery after photobleaching is complete
      and homogeneous in all cases, but in minimal medium, the periplasm is evidently
      thicker at the cell tips. For the relevant geometries, Brownian dynamics
      simulations in model cytoplasmic and periplasmic volumes provide analytical
      formulae for extraction of accurate diffusion coefficients from readily
      measurable quantities.

PMID- 21190654
TI  - Implications of three-step swimming patterns in bacterial chemotaxis.
AB  - We recently found that marine bacteria Vibrio alginolyticus execute a cyclic
      three-step (run-reverse-flick) motility pattern that is distinctively different
      from the two-step (run-tumble) pattern of Escherichia coli. How this novel, to
      our knowledge, swimming pattern is regulated by cells of V. alginolyticus is not
      currently known, but its significance for bacterial chemotaxis is self-evident
      and will be delineated herein. Using a statistical approach, we calculated the
      migration speed of a cell executing the three-step pattern in a linear chemical
      gradient, and found that a biphasic chemotactic response arises naturally. The
      implication of such a response for the cells to adapt to ocean environments and
      its possible connection to E. coli's response are also discussed.

PMID- 21190655
TI  - A novel mechanism of modulation of 5-HT3A receptors by hydrocortisone.
AB  - Modulation of Cys-loop receptors by steroids is of physiological and
      therapeutical relevance. Nonetheless, its molecular mechanism has not been
      elucidated for serotonin (5-HT) type 3 receptors. We deciphered the mechanism of
      action of hydrocortisone (HC) at 5-HT type 3A receptors. Single-channel currents
      from the high-conductance form (~4.7 pA, -70 mV) appear as a series of long
      opening events forming bursts, which group into long clusters. Although they are
      very infrequent, subconductance events (~2.4 pA) are detected within clusters. HC
      produces a significant concentration-dependent reduction in open and burst
      durations, demonstrating open-channel block. In addition, it increases the
      appearance of subconductance levels in a concentration- and slightly voltage
      dependent manner. The amplitude of the subconductance level does not change with
      HC concentration and its open duration is briefer than that of full amplitude
      events, indicating lower open-channel stability. Dual effects are distinguished
      from macroscopic responses: HC reduces amplitude by acting from either open or
      closed states, and it increases decay rates from the open state. Thus, HC acts as
      a negative modulator of 5-HT type 3A receptors by different mechanisms: It acts
      as an open-channel blocker and it favors opening to a preexisting subconductance
      level. The latter constitutes a novel, to our knowledge, mechanism of channel
      modulation, which might be applicable to other steroids and channels.

PMID- 21190656
TI  - Determination of the Na(+)/glucose cotransporter (SGLT1) turnover rate using the
      ion-trap technique.
AB  - The Na(+)/glucose cotransporter (SGLT1) is a membrane protein that couples the
      transport of two Na(+) ions and one glucose molecule using the so-called
      alternating access mechanism. According to this principle, each cotransporter
      molecule can adopt either of two main conformations: one with the binding sites
      accessible to the extracellular solution and one with the binding sites facing
      the intracellular solution. The turnover rate (TOR) is the number of complete
      cycles that each protein performs per second. Determination of the TOR has
      important consequences for investigation of the cotransport mechanism, as none of
      the rate constants involved in mediating transport in a given direction
      (conformational changes and binding and unbinding reactions) can be slower than
      the TOR measured under the same conditions. In addition, the TOR can be used to
      estimate the number of cotransporter molecules involved in generating a given
      ensemble activity. In this study, we obtain an independent estimation of the TOR
      for human SGLT1 expressed in Xenopus laevis oocytes applying the ion-trap
      technique. This approach detects the quantity of ions released in or taken up
      from the restricted space existing between the oocyte plasma membrane and the tip
      of a large ion-selective electrode. Taking advantage of the fact that hSGLT1 in
      the absence of Na(+) can cotransport glucose with protons, we used a pH electrode
      to determine a TOR of 8.00 +/- 1.3 s-1 in the presence of 35 mM alpha-methyl
      glucose at -150 mV (pH 5.5). For the same group of oocytes, a TOR of 13.3 +/- 2.4
      s-1 was estimated under near-V(max) conditions, i.e., in the presence of 90 mM
      Na(+) and 5 mM alpha-methyl-glucose. Under these circumstances, the average
      cotransport current was -1.08 +/- 0.61 MUA (n = 14), and this activity was
      generated by an average of 3.6 +/- 0.7 * 1011 cotransporter molecules/oocyte.

PMID- 21190657
TI  - Mapping the importance of four factors in creating monovalent ion selectivity in
      biological molecules.
AB  - The ability of macrocycles, enzymes, ion channels, transporters, and DNA to
      differentiate among ion types is often crucial to their function. Using molecular
      dynamics simulations on both detailed systems and simple models, we quantify the
      importance of several factors which affect the ion selectivity of such molecules,
      including the number of coordinating ligands, their dipole moment, and their
      vibrational motion. The information resulting from our model systems is distilled
      into a series of selectivity maps that can be used to read off the relative free
      energy associated with binding of different ions, and to provide an estimate of
      the importance of the various factors. Although our maps cannot capture all
      elements of real systems, it is remarkable that they produce differential site
      binding energies that are in line with experiment and more-detailed simulations
      for a variety of systems-making them useful for understanding the origins of
      selective binding and transport. The chemical nature of the coordinating ligands
      is essential for creating thermodynamic ion selectivity in flexible molecules
      (such as 18c6), but as the binding site becomes more rigid, the number of ligands
      (as in ion channels) and the reduction of thermal fluctuations (as in amino-acid
      transporters) can become important. In the future, our maps could aid in the
      determination of the local structure from binding energies and assist in the
      design of novel ion selective molecules.

PMID- 21190658
TI  - Kinetics of K(+) occlusion by the phosphoenzyme of the Na(+),K(+)-ATPase.
AB  - Investigations of K(+)-occlusion by the phosphoenzyme of Na(+),K(+)-ATPase from
      shark rectal gland and pig kidney by stopped-flow fluorimetry reveal major
      differences in the kinetics of the two enzymes. In the case of the pig enzyme, a
      single K(+)-occlusion step could be resolved with a rate constant of 342 (+/- 26)
      s-1. However, in the case of the shark enzyme, two consecutive K(+)-occlusions
      were detected with rate constants of 391 (+/- 19) s-1 and 48 (+/- 2) s-1 at 24
      degrees C and pH 7.4. A conformational change of the phosphoenzyme associated
      with K(+)-occlusion is, thus, the major rate-determining step of the shark enzyme
      under saturating concentrations of all substrates, whereas for the pig enzyme the
      major rate-determining step under the same conditions is the E2 -> E1 transition
      and its associated K(+) deocclusion and release to the cytoplasm. The differences
      in rate constants of the K(+) occlusion reactions of the two enzymes are
      paralleled by compensating changes to the rate constant for the E2 -> E1
      transition, which explains why the differences in the enzymes' kinetic behaviors
      have not previously been identified.

PMID- 21190659
TI  - Near-critical fluctuations and cytoskeleton-assisted phase separation lead to
      subdiffusion in cell membranes.
AB  - We address the relationship between membrane microheterogeneity and anomalous
      subdiffusion in cell membranes by carrying out Monte Carlo simulations of two
      component lipid membranes. We find that near-critical fluctuations in the
      membrane lead to transient subdiffusion, while membrane-cytoskeleton interaction
      strongly affects phase separation, enhances subdiffusion, and eventually leads to
      hop diffusion of lipids. Thus, we present a minimum realistic model for membrane
      rafts showing the features of both microscopic phase separation and subdiffusion.

PMID- 21190660
TI  - Two conserved residues are important for inducing highly ordered membrane domains
      by the transmembrane domain of influenza hemagglutinin.
AB  - The interaction with lipids of a synthetic peptide corresponding to the
      transmembrane domain of influenza hemagglutinin was investigated by means of
      electron spin resonance. A detailed analysis of the electron spin resonance
      spectra from spin-labeled phospholipids revealed that the major effect of the
      peptide on the dynamic membrane structure is to induce highly ordered membrane
      domains that are associated with electrostatic interactions between the peptide
      and negatively charged lipids. Two highly conserved residues in the peptide were
      identified as being important for the membrane ordering effect. Aggregation of
      large unilamellar vesicles induced by the peptide was also found to be correlated
      with the membrane ordering effect of the peptide, indicating that an increase in
      membrane ordering, i.e., membrane dehydration, is important for vesicle
      aggregation. The possibility that hydrophobic interaction between the highly
      ordered membrane domains plays a role in vesicle aggregation and viral fusion is
      discussed.

PMID- 21190661
TI  - Solid-state 2H NMR shows equivalence of dehydration and osmotic pressures in
      lipid membrane deformation.
AB  - Lipid bilayers represent a fascinating class of biomaterials whose properties are
      altered by changes in pressure or temperature. Functions of cellular membranes
      can be affected by nonspecific lipid-protein interactions that depend on bilayer
      material properties. Here we address the changes in lipid bilayer structure
      induced by external pressure. Solid-state 2H NMR spectroscopy of phospholipid
      bilayers under osmotic stress allows structural fluctuations and deformation of
      membranes to be investigated. We highlight the results from NMR experiments
      utilizing pressure-based force techniques that control membrane structure and
      tension. Our 2H NMR results using both dehydration pressure (low water activity)
      and osmotic pressure (poly(ethylene glycol) as osmolyte) show that the segmental
      order parameters (S(CD)) of DMPC approach very large values of ~ 0.35 in the
      liquid-crystalline state. The two stresses are thermodynamically equivalent,
      because the change in chemical potential when transferring water from the
      interlamellar space to the bulk water phase corresponds to the induced pressure.
      This theoretical equivalence is experimentally revealed by considering the solid
      state 2H NMR spectrometer as a virtual osmometer. Moreover, we extend this
      approach to include the correspondence between osmotic pressure and hydrostatic
      pressure. Our results establish the magnitude of the pressures that lead to
      significant bilayer deformation including changes in area per lipid and
      volumetric bilayer thickness. We find that appreciable bilayer structural changes
      occur with osmotic pressures in the range of 10-100 atm or lower. This research
      demonstrates the applicability of solid-state 2H NMR spectroscopy together with
      bilayer stress techniques for investigating the mechanism of pressure sensitivity
      of membrane proteins.

PMID- 21190662
TI  - Bacterial lipopolysaccharide promotes destabilization of lung surfactant-like
      films.
AB  - The airspaces are lined with a dipalmitoylphosphatidylcholine (DPPC)-rich film
      called pulmonary surfactant, which is named for its ability to maintain normal
      respiratory mechanics by reducing surface tension at the air-liquid interface.
      Inhaled airborne particles containing bacterial lipopolysaccharide (LPS) may
      incorporate into the surfactant monolayer. In this study, we evaluated the effect
      of smooth LPS (S-LPS), containing the entire core oligosaccharide region and the
      O-antigen, on the biophysical properties of lung surfactant-like films composed
      of either DPPC or DPPC/palmitoyloleoylphosphatidylglycerol (POPG)/palmitic acid
      (PA) (28:9:5.6, w/w/w). Our results show that low amounts of S-LPS fluidized DPPC
      monolayers, as demonstrated by fluorescence microscopy and changes in the
      compressibility modulus. This promoted early collapse and prevented the
      attainment of high surface pressures. These destabilizing effects could not be
      relieved by repeated compression-expansion cycles. Similar effects were observed
      with surfactant-like films composed of DPPC/POPG/PA. On the other hand, the
      interaction of SP-A, a surfactant membrane-associated alveolar protein that also
      binds to LPS, with surfactant-like films containing S-LPS increased monolayer
      destabilization due to the extraction of lipid molecules from the monolayer,
      leading to the dissolution of monolayer material in the aqueous subphase. This
      suggests that SP-A may act as an LPS scavenger.

PMID- 21190663
TI  - Sequence-specific ultrasonic cleavage of DNA.
AB  - We investigated the phenomenon of ultrasonic cleavage of DNA by analyzing a large
      set of cleavage patterns of DNA restriction fragments using polyacrylamide gel
      electrophoresis. The cleavage intensity of individual phosphodiester bonds was
      found to depend on the nucleotide sequence and the position of the bond with
      respect to the ends of the fragment. The relative intensities of cleavage of the
      central phosphodiester bond in 16 dinucleotides and 256 tetranucleotides were
      determined by multivariate statistical analysis. We observed a remarkable
      enhancement of the mean values of the relative intensities of cleavage (cleavage
      rates) in phosphodiester bonds following deoxycytidine, which diminished in the
      row of dinucleotides: d(CpG) > d(CpA) > d(CpT) >> d(CpC). The cleavage rates for
      all pairs of complementary dinucleotides were significantly different from each
      other. The effect of flanking nucleotides in tetranucleotides on cleavage rates
      of all 16 types of central dinucleotides was also statistically significant. The
      sequence-dependent ultrasonic cleavage rates of dinucleotides are consistent with
      reported data on the intensity of the conformational motion of their 5'
      deoxyribose. As a measure of local conformational dynamics, cleavage rates may be
      useful for characterizing functional regions of the genome.

PMID- 21190664
TI  - Roles of DNA looping in enhancer-blocking activity.
AB  - Enhancer-promoter interactions in eukaryotic genomes are often controlled by
      sequence elements that block the actions of enhancers. Although the experimental
      evidence suggests that those sequence elements contribute to forming loops of
      chromatin, the molecular mechanism of how such looping affects the enhancer
      blocking activity is still largely unknown. In this article, the roles of DNA
      looping in enhancer blocking are investigated by numerically simulating the DNA
      conformation of a prototypical model system of gene regulation. The simulated
      results show that the enhancer function is indeed blocked when the enhancer is
      looped out so that it is separated from the promoter, which explains experimental
      observations of gene expression in the model system. The local structural
      distortion of DNA caused by looping is important for blocking, so the ability of
      looping to block enhancers can be lost when the loop length is much larger than
      the persistence length of the chain.

PMID- 21190665
TI  - Efficient light harvesting in a dark, hot, acidic environment: the structure and
      function of PSI-LHCI from Galdieria sulphuraria.
AB  - Photosystem I-light harvesting complex I (PSI-LHCI) was isolated from the
      thermoacidophilic red alga Galdieria sulphuraria, and its structure, composition,
      and light-harvesting function were characterized by electron microscopy, mass
      spectrometry, and ultrafast optical spectroscopy. The results show that Galdieria
      PSI is a monomer with core features similar to those of PSI from green algae, but
      with significant differences in shape and size. A comparison with the crystal
      structure of higher plant (pea) PSI-LHCI indicates that Galdieria PSI binds seven
      to nine light-harvesting proteins. Results from ultrafast optical spectroscopy
      show that the functional coupling of the LHCI proteins to the PSI core is tighter
      than in other eukaryotic PSI-LHCI systems reported thus far. This tight coupling
      helps Galdieria perform efficient light harvesting under the low-light conditions
      present in its natural endolithic habitat.

PMID- 21190666
TI  - Allosteric suppression of HIV-1 reverse transcriptase structural dynamics upon
      inhibitor binding.
AB  - Efavirenz is a second-generation nonnucleoside reverse transcriptase inhibitor
      (NNRTI) and a common component of clinically approved anti-AIDS regimens. NNRTIs
      are noncompetitive inhibitors that bind in a hydrophobic pocket in the p66
      subunit of reverse transcriptase (RT) ~10 A from the polymerase active site.
      Hydrogen exchange mass spectrometry (HXMS) shows that efavirenz binding reduces
      molecular flexibility in multiple regions of RT heterodimer in addition to the
      NNRTI binding site. Of the 47 peptic fragments monitored by HXMS, 15 showed
      significantly altered H/D exchange rates in the presence of efavirenz. The slow
      cooperative unfolding of a beta-sheet in the NNRTI binding pocket, which was
      previously observed in unliganded RT, is dramatically suppressed by efavirenz.
      HXMS also defines an extensive network of allosterically coupled sites, including
      four distinct regions of allosteric stabilization, and one region of allosteric
      destabilization. The effects of efavirenz binding extend > 60 A from the NNRTI
      binding pocket. Allosteric changes to the structural dynamics propagate to the
      thumb and connection subdomains and RNase H domain of the p66 subunit as well as
      the thumb and palm subdomains of the p51 subunit. These allosteric regions may
      represent potential new drug targets.

PMID- 21190667
TI  - Investigating the refolding pathway of human acidic fibroblast growth factor
      (hFGF-1) from the residual structure(s) obtained by denatured-state
      hydrogen/deuterium exchange.
AB  - Human fibroblast growth factor 1 (hFGF-1) consists of 12 anti-parallel beta
      strands arranged into a beta-trefoil architecture. We directly measured
      hydrogen/deuterium exchange rates on the urea-denatured hFGF-1 to obtain the
      information with regard to the persistent residual interaction(s) in the unfolded
      hFGF-1. Thirty-eight residues whose heteronuclear single quantum coherence cross
      peaks can be observed after exchange show higher protections than those predicted
      for the same residues in a random coil conformation, suggesting the existence of
      residual structure(s). The urea-denaturation of hFGF-1 tested by both circular
      dichroism and fluorescence spectroscopy indicated that the unfolding process is a
      cooperative two-state process and that the residual structures observed did not
      originate from the existence of a partially structured intermediate. The
      coincident disappearance of the native heteronuclear single quantum coherence
      cross-peaks during the urea-denaturation process suggests that the residual
      structures observed contain no nativelike interactions. The protected residues
      (fold ons) in the urea-denatured state are mostly those that exchange slowly in
      the native state H/D exchange. The distribution of these fold ons in the native
      structure of hFGF-1 suggests that the refolding starts by collisions between the
      residual structures (microdomains) between the beta-strands VI and VII, and
      between the beta-strands II and III, which appear to be two independent refolding
      coordinates during the refolding process.

PMID- 21190668
TI  - Dissociation of bimolecular alphaIIbbeta3-fibrinogen complex under a constant
      tensile force.
AB  - The regulated ability of integrin alphaIIbbeta3 to bind fibrinogen plays a
      crucial role in platelet aggregation, adhesion, and hemostasis. Employing an
      optical-trap-based electronic force clamp, we studied the thermodynamics and
      kinetics of alphaIIbbeta3-fibrinogen bond formation and dissociation under
      constant unbinding forces, mimicking the forces of physiologic blood shear on a
      thrombus. The distribution of bond lifetimes was bimodal, indicating that the
      alphaIIbbeta3-fibrinogen complex exists in two bound states with different
      mechanical stability. The alphaIIbbeta3 antagonist, abciximab, inhibited binding
      without affecting the unbinding kinetics, whereas Mn2(+) biased the alphaIIbbeta3
      fibrinogen complex to the strong bound state with reduced off-rate. The average
      bond lifetimes decreased exponentially with increasing pulling force from ~5 pN
      to 50 pN, suggesting that in this force range the alphaIIbbeta3-fibrinogen
      interactions are classical slip bonds. We found no evidence for catch bonds,
      which is consistent with the known lack of shear-enhanced platelet adhesion on
      fibrinogen-coated surfaces. Taken together, these data provide important
      quantitative and qualitative characteristics of alphaIIbbeta3-fibrinogen binding
      and unbinding that underlie the dynamics of platelet adhesion and aggregation in
      blood flow.

PMID- 21190669
TI  - Polymer-based catch-bonds.
AB  - Catch-bonds refer to the counterintuitive notion that the average lifetime of a
      bond has a maximum at a nonzero applied force. They have been found in several
      ligand-receptor pairs and their origin is still a topic of debate. Here, we use
      coarse-grained simulations and kinetic theory to demonstrate that a multimeric
      protein, with self-interacting domain pairs, can display catch-bond behavior. Our
      model is motivated by one of the largest proteins in the human body, the von
      Willebrand Factor, which has been found to display this behavior. In particular,
      our model polymer consists of a series of repeating units that self-interact with
      their nearest neighbors along the chain. Each of the units mimics a domain of the
      protein. Apart from the short-range specific interaction, we also include a
      linker chain that will hold the domains together if unbinding occurs. This linker
      molecule represents the sequence of unfolded amino acids that connect contiguous
      domains, as is typically found in multidomain proteins. The units also interact
      with an immobilized ligand, but the interaction is masked by the presence of the
      self-interacting neighbor along the chain. Our results show that this model
      displays all the features of catch-bonds because the average lifetime of a
      binding event between the polymer and the immobilized receptor has a maximum at a
      nonzero pulling force of the polymer. The effects of the energy barriers for
      detaching the masking domain and the ligand from the binding domain, as well as
      the effects of the properties of the polypeptide chain connecting the contiguous
      domains, are also studied. Our study suggests that multimeric proteins can engage
      in catch-bonds if their self-interactions are carefully tuned, and this mechanism
      presumably plays a major role in the mechanics of extracellular proteins that
      share a multidomain character. Furthermore, our biomimetic design clearly shows
      how one could build and tune macromolecules that exhibit catch-bond
      characteristics.

PMID- 21190670
TI  - Stoichiometry and affinity of the human serum albumin-Alzheimer's Abeta peptide
      interactions.
AB  - A promising strategy to control the aggregation of the Alzheimer's Abeta peptide
      in the brain is the clearance of Abeta from the central nervous system into the
      peripheral blood plasma. Among plasma proteins, human serum albumin plays a
      critical role in the Abeta clearance to the peripheral sink by binding to Abeta
      oligomers and preventing further growth into fibrils. However, the stoichiometry
      and the affinities of the albumin-Abeta oligomer interactions are still to be
      fully characterized. For this purpose, here we investigate the Abeta oligomer
      albumin complexes through a novel and generally applicable experimental strategy
      combining saturation transfer and off-resonance relaxation NMR experiments with
      ultrafiltration, domain deletions, and dynamic light scattering. Our results show
      that the Abeta oligomers are recognized by albumin through sites that are evenly
      partitioned across the three albumin domains and that bind the Abeta oligomers
      with similar dissociation constants in the 1-100 nM range, as assessed based on a
      Scatchard-like model of the albumin inhibition isotherms. Our data not only
      explain why albumin is able to inhibit amyloid formation at physiological nM
      Abeta concentrations, but are also consistent with the presence of a single high
      affinity albumin-binding site per Abeta protofibril, which avoids the formation
      of extended insoluble aggregates.

PMID- 21190671
TI  - Structural and mechanical properties of TTR105-115 amyloid fibrils from
      compression experiments.
AB  - Amyloid fibrils, originally associated with neurodegenerative diseases, are now
      recognized to have interesting mechanical properties. By using synchrotron x-ray
      diffraction at high pressure in a diamond anvil cell we determined the bulk
      modulus of TTR105-115 amyloid fibrils in water and in silicone oil to be 2.6 and
      8.1 GPa, respectively. The compression characteristics of the fibrils are quite
      different in the two media, revealing the presence of cavities along the axis of
      the fibrils, but not between the beta-sheets, which are separated by a dry
      interface as in a steric zipper motif. Our results emphasize the importance of
      peptide packing in determining the structural and mechanical properties of
      amyloid fibrils.

PMID- 21190672
TI  - X-ray diffraction from membrane protein nanocrystals.
AB  - Membrane proteins constitute > 30% of the proteins in an average cell, and yet
      the number of currently known structures of unique membrane proteins is < 300. To
      develop new concepts for membrane protein structure determination, we have
      explored the serial nanocrystallography method, in which fully hydrated protein
      nanocrystals are delivered to an x-ray beam within a liquid jet at room
      temperature. As a model system, we have collected x-ray powder diffraction data
      from the integral membrane protein Photosystem I, which consists of 36 subunits
      and 381 cofactors. Data were collected from crystals ranging in size from 100 nm
      to 2 MUm. The results demonstrate that there are membrane protein crystals that
      contain < 100 unit cells (200 total molecules) and that 3D crystals of membrane
      proteins, which contain < 200 molecules, may be suitable for structural
      investigation. Serial nanocrystallography overcomes the problem of x-ray damage,
      which is currently one of the major limitations for x-ray structure determination
      of small crystals. By combining serial nanocrystallography with x-ray free
      electron laser sources in the future, it may be possible to produce molecular
      resolution electron-density maps using membrane protein crystals that contain
      only a few hundred or thousand unit cells.

PMID- 21190673
TI  - Detection of membrane protein two-dimensional crystals in living cells.
AB  - It is notoriously difficult to grow membrane protein crystals and solve membrane
      protein structures. Improved detection and screening of membrane protein crystals
      are needed. We have shown here that second-order nonlinear optical imaging of
      chiral crystals based on second harmonic generation can provide sensitive and
      selective detection of two-dimensional protein crystalline arrays with
      sufficiently low background to enable crystal detection within the membranes of
      live cells. The method was validated using bacteriorhodopsin crystals generated
      in live Halobacterium halobium bacteria and confirmed by electron microscopy from
      the isolated crystals. Additional studies of alphavirus glycoproteins indicated
      the presence of localized crystalline domains associated with virus budding from
      mammalian cells. These results suggest that in vivo crystallization may provide a
      means for expediting membrane protein structure determination for proteins
      exhibiting propensities for two-dimensional crystal formation.

PMID- 21190674
TI  - In vivo NMR metabolic profiling of Fabrea salina reveals sequential defense
      mechanisms against ultraviolet radiation.
AB  - Fabrea salina is a hypersaline ciliate that is known to be among the strongest
      ultraviolet (UV)-resistant microorganisms; however, the molecular mechanisms of
      this resistance are almost unknown. By means of in vivo NMR spectroscopy, we
      determined the metabolic profile of living F. salina cells exposed to visible
      light and to polychromatic UV-B + UV-A + Vis radiation for several different
      exposure times. We used unsupervised pattern-recognition analysis to compare
      these profiles and discovered some metabolites whose concentration changed
      specifically upon UV exposure and in a dose-dependent manner. This variation was
      interpreted in terms of a two-phase cell reaction involving at least two
      different pathways: an early response consisting of degradation processes,
      followed by a late response activating osmoprotection mechanisms. The first step
      alters the concentration of formate, acetate, and saturated fatty-acid
      metabolites, whereas the osmoprotection modifies the activity of betaine moieties
      and other functionally related metabolites. In the latter pathway, alanine,
      proline, and sugars suggest a possible incipient protein synthesis as defense
      and/or degeneration mechanisms. We conclude that NMR spectroscopy on in vivo
      cells is an optimal approach for investigating the effect of UV-induced stress on
      the whole metabolome of F. salina because it minimizes the invasiveness of the
      measurement.

PMID- 21190675
TI  - Investigating antibody interactions with a polar liquid using terahertz pulsed
      spectroscopy.
AB  - In this article, we use terahertz spectroscopy to study the dielectric properties
      of the peroxidase-conjugated affinity purified goat anti-cat immunoglobulin G and
      the fluorescein-conjugated affinity purified goat anti-cat immunoglobulin G when
      they interact with polar liquids. The influence of protein concentration, as well
      as presence of glycerol as a cosolvent, is determined by estimation of the
      effective hydration shell radius of the protein in solution. The dielectric
      spectra in this study are measured over the frequency range 0.1-1.3 THz and it is
      found that the dielectric properties are dependent on the type of the charges in
      the hydrogen-bonded antibodies' networks. Our results indicate that the terahertz
      dielectric properties of polar liquids are strongly affected by the presence of
      the antibody and suggest that the dielectric spectrum is particularly powerful in
      the study of structural and conformational properties of proteins. Therefore,
      terahertz spectroscopy is a very sensitive approach to investigate structural
      features of biological systems.

PMID- 21190676
TI  - Second-harmonic generation imaging of membrane potential with retinal analogues.
AB  - Second-harmonic generation (SHG) by membrane-incorporated probes is a nonlinear
      optical signal that is voltage-sensitive and the basis of a sensitive method for
      imaging membrane potential. The voltage dependence of SHG by four different
      probes, three retinoids (all-trans retinal), and two new retinal analogs, 3
      methyl-7-(4'-dimethylamino-phenyl)-2,4,6-heptatrienal (AR-3) and 3,7-dimethyl-9
      (4'-dimethylamino-phenyl)-2,4,6,8-nonatetraenal (AR-4), and a styryl dye (FM4
      64), were compared in HEK-293 cells. Results were analyzed by fitting data with
      an expression based on an electrooptic mechanism for SHG, which depends on the
      complex-valued first- and second-order nonlinear electric susceptibilities (chi2
      and chi3) of the probe. This gave values for the voltage sensitivity at the
      cell's resting potential, the voltage where the SHG is minimal, and the amplitude
      of the signal at that voltage for each of the four compounds. These measures show
      that chi2 and chi3 are complex numbers for all compounds except all-trans
      retinal, consistent with the proximities of excitation and/or emission
      wavelengths to molecular resonances. Estimates of probe orientation and location
      in the membrane electric field show that, for the far-from-resonance case, the
      shot noise-limited signal/noise ratio depends on the location of the probe in the
      membrane, and on chi3 but not on chi2.

PMID- 21190677
TI  - Antibody-unfolding and metastable-state binding in force spectroscopy and
      recognition imaging.
AB  - Force spectroscopy and recognition imaging are important techniques for
      characterizing and mapping molecular interactions. In both cases, an antibody is
      pulled away from its target in times that are much less than the normal residence
      time of the antibody on its target. The distribution of pulling lengths in force
      spectroscopy shows the development of additional peaks at high loading rates,
      indicating that part of the antibody frequently unfolds. This propensity to
      unfold is reversible, indicating that exposure to high loading rates induces a
      structural transition to a metastable state. Weakened interactions of the
      antibody in this metastable state could account for reduced specificity in
      recognition imaging where the loading rates are always high. The much weaker
      interaction between the partially unfolded antibody and target, while still
      specific (as shown by control experiments), results in unbinding on millisecond
      timescales, giving rise to rapid switching noise in the recognition images. At
      the lower loading rates used in force spectroscopy, we still find discrepancies
      between the binding kinetics determined by force spectroscopy and those
      determined by surface plasmon resonance-possibly a consequence of the short
      tethers used in recognition imaging. Recognition imaging is nonetheless a
      powerful tool for interpreting complex atomic force microscopy images, so long as
      specificity is calibrated in situ, and not inferred from equilibrium binding
      kinetics.

PMID- 21190678
TI  - Noninvasive detection and imaging of molecular markers in live cardiomyocytes
      derived from human embryonic stem cells.
AB  - Raman microspectroscopy (RMS) was used to detect and image molecular markers
      specific to cardiomyocytes (CMs) derived from human embryonic stem cells (hESCs).
      This technique is noninvasive and thus can be used to discriminate individual
      live CMs within highly heterogeneous cell populations. Principal component
      analysis (PCA) of the Raman spectra was used to build a classification model for
      identification of individual CMs. Retrospective immunostaining imaging was used
      as the gold standard for phenotypic identification of each cell. We were able to
      discriminate CMs from other phenotypes with >97% specificity and >96%
      sensitivity, as calculated with the use of cross-validation algorithms (target
      100% specificity). A comparison between Raman spectral images corresponding to
      selected Raman bands identified by the PCA model and immunostaining of the same
      cells allowed assignment of the Raman spectral markers. We conclude that glycogen
      is responsible for the discrimination of CMs, whereas myofibril proteins have a
      lesser contribution. This study demonstrates the potential of RMS for allowing
      the noninvasive phenotypic identification of hESC progeny. With further
      development, such label-free optical techniques may enable the separation of high
      purity cell populations with mature phenotypes, and provide repeated measurements
      to monitor time-dependent molecular changes in live hESCs during differentiation
      in vitro.

PMID- 21190679
TI  - Excited-state dynamics of protochlorophyllide revealed by subpicosecond infrared
      spectroscopy.
AB  - To gain a better understanding of the light-induced reduction of
      protochlorophyllide (PChlide) to chlorophyllide as a key regulatory step in
      chlorophyll synthesis, we performed transient infrared absorption measurements on
      PChlide in d4-methanol. Excitation in the Q-band at 630 nm initiates dynamics
      characterized by three time constants: tau1 = 3.6 +/- 0.2, tau2 = 38 +/- 2, and
      tau3 = 215 +/- 8 ps. As indicated by the C13'=O carbonyl stretching mode in the
      electronic ground state at 1686 cm-1, showing partial ground-state recovery, and
      in the excited electronic state at 1625 cm-1, showing excited-state decay, tau2
      describes the formation of a state with a strong change in electronic structure,
      and tau3 represents the partial recovery of the PChlide electronic ground state.
      Furthermore, tau1 corresponds with vibrational energy relaxation. The observed
      kinetics strongly suggest a branched reaction scheme with a branching ratio of
      0.5 for the path leading to the PChlide ground state on the 200 ps timescale and
      the path leading to a long-lived state (>>700 ps). The results clearly support a
      branched reaction scheme, as proposed previously, featuring the formation of an
      intramolecular charge transfer state with ~25 ps, its decay into the PChlide
      ground state with 200 ps, and a parallel reaction path to the long-lived PChlide
      triplet state.

PMID- 21190680
TI  - Inhibition of proinflammatory macrophage responses and lymphocyte proliferation
      in vitro by ethyl acetate leaf extract from Daphne gnidium.
AB  - Medicinal plants are considered immunomodulatory as they display various
      biological activities. There is no report addressing the anti-inflammatory
      effects of Daphne gnidium. In this study, we investigated the effects of D.
      gnidium ethyl acetate (EA) leaf extract on mice immune cell function in vitro.
      Production of pro-inflammatory cytokines (IL-1beta and TNF-alpha), cyclooxygenase
      2-derived prostaglandinE2 (PGE2) and iNOS-II-synthesised nitric oxide (NO) were
      examined. EA extract effect on mitogen-induced lymphocyte proliferation was also
      investigated. We reported for the first time that D. gnidium EA leaf extract dose
      dependently inhibits macrophage proinflammatory function by reducing LPS-induced
      production of IL-1beta, TNF-alpha, COX-2-derived PGE2 and iNOS-II-synthesised NO.
      Mitogen-induced lymphocyte proliferation was also dose-dependently inhibited by
      the extract. Lectin-induced response appears to be more sensitive to the
      suppressive effects of the extract than LPS-stimulated response. Collectively,
      these results demonstrate that D. gnidium EA leaf extract acts as an in vitro
      anti-inflammatory factor by inhibiting mice macrophage and lymphocyte activities.

PMID- 21190681
TI  - The zymogen granule protein 2 (GP2) binds to scavenger receptor expressed on
      endothelial cells I (SREC-I).
AB  - The pancreatic zymogen granule membrane protein (GP2) is expressed by pancreatic
      acinar cells and M cells of the ileum. GP2 is the closest related homologue of
      the urine resident Tamm-Horsfall protein (THP). Recently, it was shown that THP
      is a ligand of various scavenger receptors (SRs). Therefore, we were interested,
      if GP2 has similar properties. cDNA of different SRs was stably transfected into
      a murine thymoma cell line. GP2 was recombinantly expressed, purified and
      biotinylated. Binding or uptake of GP2 by transfected cells or monocyte-derived
      dendritic cells (moDCs) was analyzed by flow-cytometry. GP2 is a binding partner
      of the scavenger receptor expressed on endothelial cells I (SREC-I) but not of SR
      AI and SR-BI. The dissociation constant (K(d)) of GP2 binding to SREC-I is
      41.3nM. SREC transfected cells are able to internalize GP2. moDCs express SREC-I
      and also bind and internalize GP2. Inhibition of SREC-I on moDCs with anti-SREC-I
      antibodies does not result in a decreased GP2 binding. Interaction of GP2 with
      SREC-I and uptake might have profound effects in antigen clearance and mediation
      of the immune response. In addition to SREC-I other presently unknown receptors
      for GP2 on DCs might be involved in this process.

PMID- 21190682
TI  - New perspectives on perspective-taking mechanisms and the out-of-body experience.

PMID- 21190683
TI  - Do brain tumours allow valid conclusions on the localisation of human brain
      functions?

PMID- 21190684
TI  - Application of the hybrid approach to the benchmark dose of urinary cadmium as
      the reference level for renal effects in cadmium polluted and non-polluted areas
      in Japan.
AB  - OBJECTIVES: The aim of this study was to evaluate the reference level of urinary
      cadmium (Cd) that caused renal effects. An updated hybrid approach was used to
      estimate the benchmark doses (BMDs) and their 95% lower confidence limits (BMDL)
      in subjects with a wide range of exposure to Cd. METHODS: The total number of
      subjects was 1509 (650 men and 859 women) in non-polluted areas and 3103 (1397
      men and 1706 women) in the environmentally exposed Kakehashi river basin. We
      measured urinary cadmium (U-Cd) as a marker of long-term exposure, and beta2
      microglobulin (beta2-MG) as a marker of renal effects. The BMD and BMDL that
      corresponded to an additional risk (BMR) of 5% were calculated with background
      risk at zero exposure set at 5%. RESULTS: The U-Cd BMDL for beta2-MG was 3.5MUg/g
      creatinine in men and 3.7 MUg/g creatinine in women. CONCLUSIONS: The BMDL values
      for a wide range of U-Cd were generally within the range of values measured in
      non-polluted areas in Japan. This indicated that the hybrid approach is a robust
      method for different ranges of cadmium exposure. The present results may
      contribute further to recent discussions on health risk assessment of Cd
      exposure.

PMID- 21190685
TI  - Thinking ahead of the surgeon. An interview study to identify scrub nurses' non
      technical skills.
AB  - BACKGROUND: Efforts to reduce adverse event rates in healthcare have revealed the
      importance of identifying the essential non-technical (cognitive and social)
      skills for safe and effective performance. Previous research on non-technical
      skills for operating theatre staff has concentrated on doctors rather than
      nursing professionals. OBJECTIVES: The aim of the study was to identify the
      critical non-technical skills that are essential for safe and effective
      performance as an operating theatre scrub nurse. METHODS: Experienced scrub
      nurses (n = 25) and consultant surgeons (n = 9) from four Scottish hospitals were
      interviewed using a semi-structured format. The protocols were designed to
      identify the main social and cognitive skills required by scrub nurses.
      Interviews were digitally recorded, transcribed verbatim and independently coded
      to extract behaviours in order to produce a list of the main non-technical skills
      for safe and effective scrub nurse performance. RESULTS: The non-technical skills
      of situation awareness, communication, teamwork, task management and coping with
      stress were identified as key to successful scrub nurse task performance.
      Component sets of behaviours for each of these categories were also noted.
      CONCLUSION: The interviews with subject matter experts from scrub nursing and
      surgery produced preliminary evidence that situation awareness, communication,
      teamwork and coping with stress are the principal non-technical skills required
      for effective performance as a scrub nurse.

PMID- 21190686
TI  - Report of the 33rd annual conference of the European Lipoprotein Club, Tutzing, 6
      9 September 2010.

PMID- 21190687
TI  - Thousand fold concentration of an alkaloid in capillary zone electrophoresis by
      micelle to solvent stacking.
AB  - In this paper, the co-solvent of methanol-water was used to facilitate the sodium
      dodecyl sulfate (SDS) micelles collapse, thereby inducing the on-line sample
      focusing technique of micelle to solvent stacking (MSS). To demonstrate this
      stacking method, the mechanism of micelles collapse in co-solvent was discussed.
      The details of the required conditions were investigated and the optimized
      conditions were: running buffer, 20mM H(3)BO(3) and 20mM NaH(2)PO(4) solution (pH
      4.0); micellar sample matrix, 20mM SDS, 20mM H(3)BO(3) and 20mM NaH(2)PO(4)
      solution (pH 4.0); co-solvent buffer, 20mM H(3)BO(3) and 20mM NaH(2)PO(4) in
      methanol/water (90:10, v/v). The validity of the developed method was tested
      using cationic alkaloid compounds (ephedrine and berberine) as model analytes.
      Under the optimized conditions, this proposed method afforded limits of detection
      (LODs) of 0.5 and 1.1ng/mL with 300 and 1036-fold improvements in sensitivity for
      ephedrine and berberine, respectively, within 15min.

PMID- 21190688
TI  - Selective extraction of triazine herbicides based on a combination of membrane
      assisted solvent extraction and molecularly imprinted solid phase extraction.
AB  - A selective extraction technique based on the combination of membrane assisted
      solvent extraction and molecularly imprinted solid phase extraction for triazine
      herbicides in food samples was developed. Simazine, atrazine, prometon,
      terbumeton, terbuthylazine and prometryn were extracted from aqueous food samples
      into a hydrophobic polypropylene membrane bag containing 1000MUL of toluene as
      the acceptor phase along with 100mg of MIP particles. In the acceptor phase, the
      compounds were re-extracted onto MIP particles. The extraction technique was
      optimised for the type of organic acceptor solvent, amount of molecularly
      imprinted polymers particles in the organic acceptor phase, extraction time and
      addition of salt. Toluene as the acceptor phase was found to give higher triazine
      binding onto MIP particles compared to hexane and cyclohexane. Extraction time of
      120min and 100mg of MIP were found to be optimum parameters. Addition of salt
      increased the extraction efficiency for more polar triazines. The selectivity of
      the technique was demonstrated by extracting spiked cow pea and corn extracts
      where clean chromatograms were obtained compared to only membrane assisted
      solvent extraction or only molecularly imprinted solid phase extraction. The
      study revealed that this combination may be a simple way of selectively
      extracting compounds in complex samples.

PMID- 21190689
TI  - Distribution ratio, distribution constant and partition coefficient.
      Countercurrent chromatography retention of benzoic acid.
AB  - There is some confusion in chromatography between terms such as solute
      distribution ratio, distribution constant and partition coefficient. These terms
      are very precisely defined in the field of liquid-liquid systems and liquid
      liquid extraction as well as in the field of chromatography with sometimes
      conflicting definitions. Countercurrent chromatography (CCC) is a chromatographic
      technique in which the stationary phase is a support-free liquid. Since the
      mobile phase is also liquid, biphasic liquid systems are used. This work focuses
      on the exact meaning of the terms since there are consequences on experimental
      results. The retention volumes of solutes in CCC are linearly related to their
      distribution ratios. The partition coefficient that should be termed (IUPAC
      recommendation) distribution constant is linked to a single definite species.
      Using benzoic acid that can dimerize in heptane and ionize in aqueous phase and
      an 18 mL hydrodynamic CCC column, the role and relationships between parameters
      and the consequences on experimental peak position and shape are discussed. If
      the heptane/water distribution constant (marginally accepted to be called
      partition coefficient) of benzoic acid is 0.2 at 20  degrees C and can be
      tabulated in books, its CCC measured distribution ratio or distribution
      coefficient can change between zero (basic aqueous mobile phase) and more than 25
      (acidic aqueous mobile phase and elevated concentration). Benzoic acid
      distribution ratio and partition coefficient coincide only when both dimerization
      and ionization are quenched, i.e. at very low concentration and pH 2. It is
      possible to quench dimerization adding butanol in the heptane/water system.
      However, butanol additions also affect the partition coefficient of benzoic acid
      greatly by increasing it.

PMID- 21190690
TI  - Evaluation of a method based on liquid chromatography-diode array detector-tandem
      mass spectrometry for a rapid and comprehensive characterization of the fat
      soluble vitamin and carotenoid profile of selected plant foods.
AB  - The feasibility of using reversed-phase liquid chromatography/diode array/tandem
      mass spectrometry (LC-DAD-MS/MS) for a rapid and comprehensive profiling of fat
      soluble vitamins and pigments in some foods of plant origin (maize flour, green
      and golden kiwi) was evaluated. The instrumental approach was planned for
      obtaining two main outcomes within the same chromatographic run: (i) the
      quantitative analysis of ten target analytes, whose standards are commercially
      available; (ii) the screening of pigments occurring in the selected matrices. The
      quantitative analysis was performed simultaneously for four carotenoids (lutein,
      zeaxanthin, beta-cryptoxanthin, and beta-carotene) and six compounds with fat
      soluble activity (alpha-tocopherol, delta-tocopherol, gamma-tocopherol,
      ergocalciferol, phylloquinone and menaquinone-4), separated on a C30 reversed
      phase column and detected by atmospheric pressure chemical ionization (APCI)
      tandem mass spectrometry, operating in Selected Reaction Monitoring (SRM) mode.
      Extraction procedure was based on matrix solid-phase dispersion with recoveries
      of all compounds under study exceeding 78 and 60% from maize flour and kiwi,
      respectively. The method intra-day precision ranged between 3 and 7%, while the
      inter-day one was below 12%. The mild isolation conditions precluded artefacts
      creation, such as cis-isomerization phenomena for carotenoids. During the
      quantitative LC-SRM determination of the ten target analytes, the identification
      power of the diode array detector joined to that of the triple quadrupole (QqQ)
      allowed the tentatively identification of several pigments (chlorophylls and
      carotenoids), without the aid of standards, on the basis of: (i) the UV-vis
      spectra recorded in the range of 200-700nm; (ii) the expected retention time;
      (iii) the two SRM transitions, chosen for the target carotenoids but also common
      to many of isomeric carotenoids occurring in the selected foods.

PMID- 21190691
TI  - Application of a liquid chromatographic procedure for the analysis of penicillin
      antibiotics in biological fluids and pharmaceutical formulations using sodium
      dodecyl sulphate/propanol mobile phases and direct injection.
AB  - A direct injection liquid chromatography procedure was developed for the
      simultaneous determination of four penicillin antibiotics (amoxicillin,
      ampicillin, cloxacillin and dicloxacillin) in pharmaceutical formulations and
      physiological fluids (urine) using hybrid micellar mobile phases. These
      antimicrobials are used to treat gastrointestinal and systemic infections. The
      four penicillins were analysed using a Zorbax C18 reversed-phase column and
      detected at 210 nm. These antibiotics were separated by an interpretive
      optimisation procedure based on the accurate description of the retention and
      shape of the chromatographic peaks. Antibiotics were eluted in less than 16 min
      with no interference by the urine protein band or endogenous compounds using the
      mobile phase 0.11 M sodium dodecyl sulphate-6% propanol-0.01 M NaH(2)PO(4)
      buffered at pH 3. The method was validated according to the Food and Drug
      Administration guideline, including analytical parameters such as linearity
      (R(2)>0.993), intra- and inter-day precisions (RSD, %: 0.1-4.4 and 1.2-5.9,
      respectively), and robustness for the four compounds. This method is sensitive
      enough for the routine analysis of penicillins at therapeutic urine levels, with
      limits of detection in the 1.5-15 ng mL(-1) range and limits of quantification of
      50 ng mL(-1). Recoveries in a micellar medium and a spiked urine matrix were in
      the 92.4-108.2% and 96-110% ranges, respectively. Finally, the method was
      successfully applied to determine these antibiotics in urine samples and
      pharmaceutical formulations.

PMID- 21190692
TI  - Kinetic theory of heterogeneous nucleation; effect of nonuniform density in the
      nuclei.
AB  - The heterogeneous nucleation of a liquid from a vapor in contact with a planar
      solid surface or a solid surface with cavities is examined on the basis of the
      kinetic theory of nucleation developed by Nowakowski and Ruckenstein [J. Phys.
      Chem. 96 (1992) 2313] which is extended to nonuniform fluid density distribution
      (FDD) in the nucleus. The latter is determined under the assumption that at each
      moment the FDD in the nucleus is provided by the density functional theory (DFT)
      for a nanodrop. As a result of this assumption, the theory does not require to
      consider that the contact angle which the nucleus makes with the solid surface
      and the density of the nucleus are independent parameters since they are provided
      by the DFT. For all considered cases, the nucleation rate is higher in the
      cavities than on a planar surface and increases with increasing strength of the
      fluid-solid interactions and decreasing cavity radius. The difference is small at
      high supersaturations (small critical nuclei), but becomes larger at low
      supersaturations when the critical nucleus has a size comparable with the size of
      the cavity. The nonuniformity of the FDD in the nucleus decreases the nucleation
      rate when compared to the uniform FDD.

PMID- 21190693
TI  - Role of interface in dispersion and surface energetics of polymer nanocomposites
      containing hydrophilic POSS and layered silicates.
AB  - Three different hydrophilic nanofillers--natural and synthetic layered silicate
      as well as octaammonium polyhedral oligomeric silsesquioxane (POSS)--were
      incorporated into polyamide-6 by a solution-mixing method. The surfaces of the
      resulting polymer nanocomposites were characterized by X-ray diffraction,
      polarized optical microscopy, Fourier transform infrared spectroscopy, X-ray
      photoelectron spectroscopy and contact angle measurements. All polymer
      nanocomposites displayed enhancement in surface hydrophilicity as well as
      increase in surface free energy due to surface enrichment of the nanofillers. The
      degree of enhancement was found to depend on both nanofiller type and dispersion
      state. Interfacial interactions in the form of hydrogen bonding played an
      important role in affecting the dispersion state of the layered silicates.
      Exfoliated layered silicates caused a larger increase in hydrophilicity than
      aggregated layered silicate. On the other hand, aggregated POSS molecules were
      able to induce a large increase in hydrophilicity. Significant spreading of water
      was also observed on surfaces containing POSS molecules. Surface models have been
      proposed to explain these phenomena.

PMID- 21190694
TI  - Application of the UNIFAC model for prediction of surface tension and thickness
      of the surface layer in the binary mixtures.
AB  - Surface properties of binary mixtures of (alkanol with acetonitrile) have been
      measured by surface tension method at T=298.15 K and atmospheric pressure. The
      UNIFAC method is used for calculation activity coefficients of surface and bulk
      phases. Also, the surface tension has been predicted based on the Suarez method.
      This method combines a model for the description of surface tension of liquid
      mixtures with a UNIFAC group contribution method for the calculation of activity
      coefficient. Two techniques for calculation of molar surface areas, based on
      Paquette areas and Rasmussen areas are tested. On comparing the computed values
      of surface tension by the present approaches with experimental data, satisfactory
      results have been observed. In addition, the relative Gibbs adsorption and the
      surface mole fraction have been evaluated using this model. It is possible to
      calculate the thickness of liquid-vapor interfaces starting from surface tension
      data. A novel procedure is developed to obtain the thickness of liquid-vapor
      interfaces as a function of composition in binary systems.

PMID- 21190695
TI  - Bovine serum albumin-directed synthesis of biocompatible CdSe quantum dots and
      bacteria labeling.
AB  - A simple method was developed for preparing CdSe quantum dots (QDs) using a
      common protein (bovine serum albumin (BSA)) to sequester QD precursors (Cd(2+))
      in situ. Fluorescence (FL) and absorption spectra showed that the chelating time
      between BSA and Cd(2+), the molar ratio of BSA/Cd(2+), temperature, and pH are
      the crucial factors for the quality of QDs. The average QD particle size was
      estimated to be about 5 nm, determined by high-resolution transmission electron
      microscopy. With FL spectra, Fourier transform infrared spectra, and
      thermogravimetric analysis, an interesting mechanism was discussed for the
      formation of the BSA-CdSe QDs. The results indicate that there might be
      conjugated bonds between CdSe QDs and -OH, -NH, and -SH groups in BSA. In
      addition, fluorescence imaging suggests that the QDs we designed can successfully
      label Escherichia coli cells, which gives us a great opportunity to develop
      biocompatible tools to label bacteria cells.

PMID- 21190696
TI  - Physico-chemical mechanisms governing the adherence of starch granules on
      materials with different hydrophobicities.
AB  - The factors influencing the adherence of starch were examined to improve the
      understanding of the mechanisms affecting soiling and cleanability. Therefore an
      aqueous suspension of starch granules was sprayed on four model substrates
      (glass, stainless steel, polystyrene and PTFE) and dried, and the substrates were
      cleaned using a radial-flow cell. The morphology of the soiled surfaces and the
      substrate chemical composition were also characterized. By influencing droplet
      spreading and competition between granule-substrate and granule-granule
      interfaces regarding the action of capillary forces, substrate wettability
      affected the shape and compactness of the adhering aggregates, the efficiency of
      shear forces upon cleaning, and finally the adherence of soiling particles. The
      rate of drying had an influence explained by the duration left to capillary
      forces for acting. X-ray photoelectron spectroscopy demonstrated the presence of
      macromolecules, mainly polysaccharides, which were adsorbed from the liquid
      phase, or carried by the retracting water film and deposited at the granule
      substrate interface. These macromolecules acted as an adhesive joint, the
      properties of which seemed to be influenced by the detailed history of drying and
      subsequent exposure to humidity. In summary, the substrate surface energy affects
      the adherence of starch aggregates by different mechanisms which are all linked
      together: suspension droplet spreading, action of capillary forces, direct
      interaction with starch particles and interfacial macromolecules.

PMID- 21190697
TI  - Novel antifouling oligo(ethylene glycol) methacrylate particles via surfactant
      free emulsion polymerization.
AB  - The use of particle formulations with antifouling surface properties attracts
      increasing interest in several biotechnological applications. Majority of these
      studies utilize a poly(ethylene glycol) coating to render the corresponding
      surface nonrecognizable to biological macromolecules. Herein, we report a simple
      way to prepare novel antifouling colloids composed of oligo(ethylene glycol)
      backbones via surfactant-free emulsion polymerization. Monodisperse cross-linked
      poly(ethylene glycol) ethyl ether methacrylate particles were characterized by
      dynamic light scattering and transmission electron microscopy. The effects of
      monomer, cross-linker and initiator on particle characteristics were
      investigated. More importantly, a prominent blockage of bovine serum albumin
      adsorption was obtained for the poly(ethylene glycol)-based sub-micron (~200 nm)
      particles when compared with similar-sized poly(methyl methacrylate)
      counterparts.

PMID- 21190698
TI  - Surface chemical modifications induced on high surface area graphite and carbon
      nanofibers using different oxidation and functionalization treatments.
AB  - Two graphitic carbon materials with different edge to basal plane ratio, high
      surface area graphite (HSAG) and graphitized carbon nanofibers (CNFs), were
      oxidized by two methods, aqueous-HNO(3) wet oxidation and oxygen plasma
      oxidation. Characterization of the materials by temperature-programmed
      desorption, thermogravimetry and X-ray photoelectron and Raman spectroscopies
      indicated that the amount and nature of oxygen surface groups introduced depended
      on the oxidation method and on the structure of the original material. While
      surface sites within the layers were only oxidized by oxygen plasma, surface
      sites at the edges of graphene layers were oxidized by both treatments being the
      wet oxidation more effective. Modification of the oxidized materials with a
      diamine or a triamine molecule resulted in the formation of ammonium carboxylate
      salt species on the carbon surface.

PMID- 21190699
TI  - Interaction of cationic liposomes with cell membrane models.
AB  - The interaction of phosphatidylcholine liposomes used as cell models, with
      cationic liposomes formulated with 1,2-dimyristoyl-sn-glycero-3
      phosphatidylcholine and amphiphiles based on a pyrrolidinium headgroup was
      investigated by differential scanning calorimetry and fluorescence resonance
      energy transfer experiments. The results obtained showed that subtle variations
      in the formulation can influence lipid interactions and were correlated to a
      previous biological evaluation.

PMID- 21190700
TI  - Similarity of ST and T waveforms of 12-lead electrocardiogram acquired from
      different monitoring electrode positions.
AB  - BACKGROUND: It is not always feasible to use standard electrode placement for
      limb leads when recording the 12-lead electrocardiogram (ECG). Other electrode
      placements have been accepted during monitoring. Nonstandard electrode positions,
      however, fail to produce waveforms identical to those recorded from the distal
      limb positions that are standard for diagnostic interpretation. The purpose of
      the present study was to validate the ST-T-segment for an alternative "Lund
      system" of proximal limb electrode sites. METHODS: Twelve-lead ECGs (standard,
      Mason-Likar, and Lund lead placement) were collected from 167 patients. RESULTS:
      There were systematic differences between measurements from standard vs Mason
      Likar, but not vs the Lund system. The 95% confidence intervals of measurement
      agreement were similar or less when comparing measurements from the Lund system
      vs the first standard recording with measurements for the 2 standard recordings.
      CONCLUSION: The Lund system might constitute a uniform convention for
      "diagnostic" ECGs as well as for monitoring ECG applications with regard to ST-T
      waveforms.

PMID- 21190701
TI  - Novel methodology for the detection of exercise-induced myocardial wall motion
      abnormalities by surface electrocardiogram during exercise test.
AB  - BACKGROUND: We investigated whether ischemia-induced wall motion abnormalities
      during exercise test modify electrical vector variation. METHODS: We performed
      treadmill exercise test and thallium 201 scintigraphy in 150 normotensives. Beat
      to-beat change of direction of S wave in V(1) (reference lead) was compared with
      that of R wave in V(5) and aVF, representative of anterior and inferior walls,
      respectively. The percentage of neighboring QRS couples where S wave in V(1) and
      R wave in V(5) or aVF change toward the same direction (increase or decrease)
      constitutes V1-V5 and V1-aVF indexes. RESULTS: V1-V5 and V1-aVF indexes were
      significantly decreased in subjects with reversible anterior or inferior
      ischemia, respectively. A decrease in V1-V5 index >=0.14 defines those with
      anterior wall ischemia (sensitivity, 100%; specificity, 75.5%), whereas a
      decrease in V1-aVF index >=0.05 defines those with inferior wall ischemia
      (sensitivity, 92.3%; specificity, 61.5%). CONCLUSIONS: These novel
      electrocardiographic exercise test indexes improved significantly their
      sensitivities.

PMID- 21190702
TI  - Characterization of spheres derived from canine mammary gland adenocarcinoma cell
      lines.
AB  - There is increasing evidence for the presence of cancer stem cells in several
      solid tumors, and these cancer stem cells have a potential role in tumor
      initiation, aggression, and recurrence. The stem cell-like properties of spheres
      derived from canine mammary tumors remain largely elusive. We attempted to induce
      sphere formation using four cell lines of canine mammary adenocarcinoma, and
      characterized the spheres derived from a CHMp line in vitro and in vivo. The CHMp
      derived spheres showed predominantly CD44+CD24- population, higher expression of
      stem cell-related genes, such as CD133, Notch3 and MDR, and higher resistance to
      doxorubicin compared with the CHMp-derived adherent cells. Xenograft
      transplantations in nude mice demonstrated that only 1 * 10(4)sphere cells were
      sufficient for tumor formation. Use of the sphere assay on these sphere-derived
      tumors showed that sphere-forming cells were present in the tumors, and were
      maintained in serial transplantation. We propose that spheres derived from canine
      mammary adenocarcinoma cell lines possess a potential characteristic of cancer
      stem cells. Spheres derived from canine mammary tumors could be a powerful tool
      with which to investigate novel therapeutic drugs and to elucidate the molecular
      and cellular mechanisms that underlie tumorigenesis.

PMID- 21190703
TI  - [New elements in the diagnosis and the treatment of primary AL amyloid
      polyneuropathy and neuropathy due to POEMS syndrome].
AB  - INTRODUCTION: Primary AL amyloid polyneuropathy (AL-PN) and neuropathy due to
      POEMS syndrome (POEMS-N) are rare, associated with a monoclonal gammopathy (MG)
      IgGlambda or IgAlambda at a low rate and systemic manifestations. They are
      invalidating and life-threatening. STATE OF THE ART: AL-PN usually mimics small
      fiber length-dependent axonal polyneuropathies, but also multifocal or painful
      neuropathies, POEMS-N corresponds to a rapid ascending CIDP with MG. To confirm
      the diagnosis of AL-PN, initial investigations should identify amyloidosis on
      nerve or accessory salivary glands, to establish the type of amyloid after serum
      free light-chain (FLC) measurements. For the diagnosis of N-POEMS, diagnosis is
      based on the presence of four criteria proposed by Dispenzieri. These
      neuropathies are associated with biomarkers, useful for diagnosis and treatment
      monitoring: elevated serum level of FLC monoclonal in (AL-PN) or VEGF (N-POEMS).
      PERSPECTIVES: Early diagnosis of these neuropathies and early treatment using
      high-dose melphalan associated with an autologous hematopoietic stem cell graft
      or low monthly doses can improve the clinical manifestations and patient
      survival. CONCLUSIONS: Systematic search for monoclonal gammopathy by
      immunofixation and serum free light chains is very useful for the management of
      progressive peripheral neuropathies of unknown origin.

PMID- 21190704
TI  - [Iatrogenic venous cerebral air embolism without pulmonary manifestation: A
      retrograde mechanism?].
AB  - INTRODUCTION: Air embolism is a rare complication of various invasive medical
      procedures. Venous cerebral air embolism is usually the consequence of
      paradoxical embolism. We report a case of isolated cerebral air embolism
      resulting from a non-paradoxical mechanism. CASE REPORT: A few minutes after his
      central venous catheter had been accidentally disconnected, a 63-year-old man
      developed left-sided rhythmic jerking movements followed by left hemiplegia.
      There were no associated cardiologic or pulmonary signs. Brain CT showed air
      bubbles in the right frontal cortical sulci. The brain MRI DWI and FLAIR
      sequences showed a high intensity right frontal cortical lesion without reduction
      in ADC. Transesophageal echocardiogram did not find a patent foramen ovale.
      CONCLUSIONS: In this case of venous cerebral air embolism, the lack of any
      cardiopulmonary manifestation, the lack of a patent foramen ovale and the
      neuroradiological findings are not in favor of the hypothesis of paradoxical
      embolism. The hypothesis of retrograde venous cerebral air embolism is discussed.

PMID- 21190705
TI  - [Diagnostic pitfalls in carpal tunnel syndrome].
AB  - BACKGROUND: This review focuses on the main aspects of positive and differential
      diagnosis of carpal tunnel syndrome (CTS) in different clinical situations
      encountered in daily practice. STATE OF THE ART: Authentic CTS can be discovered
      in situations, which alter the usual presentation or therapeutic management. This
      is the case for instance in pregnant women or in the elderly subject or with
      acute motor forms where CTS discloses a focal intratunnel disorder (neuroma,
      lipoma, arterial condition, bone disorder) or a general disease (hereditary
      neuropathy, amylosis). In certain situations, the clinical manifestations suggest
      a more proximal compression of the medial nerve (round pronator, Struthers
      arcade, or superficial flexor) or an inflammatory condition (mononeuritis,
      inflammatory demyelinising neuropathy). Locoregional disease may also be
      involved, for instance a plexus (thoracobrachial outlet syndrome, post-radiation
      plexitis) or radicular condition. The clinical presentation of diffuse
      polyneuropathy with initial manifestations involving the upper limb
      (ganglioneuropathies, polyradiculoneuritis, small-fiber neuropathies) may also be
      misleading. Finally central conditions can sometimes be confused with CTS.
      CONCLUSION: A rigorous physical examination and an electroneuromyogram are
      determining to avoid diagnostic pitfalls.

PMID- 21190706
TI  - Frequency-wavenumber domain analysis of guided wavefields.
AB  - Full wavefield measurements obtained with either an air-coupled transducer
      mounted on a scanning stage or a scanning laser vibrometer can be combined with
      effective signal and imaging processing algorithms to support characterization of
      guided waves as well as detection, localization and quantification of structural
      damage. These wavefield images contain a wealth of information that clearly shows
      details of guided waves as they propagate outward from the source, reflect from
      specimen boundaries, and scatter from discontinuities within the structure. The
      analysis of weaker scattered waves is facilitated by the removal of source waves
      and the separation of wave modes, which is effectively achieved via frequency
      wavenumber domain filtering in conjunction with the subsequent analysis of the
      resulting residual signals. Incident wave removal highlights the presence and the
      location of weak scatterers, while the separation of individual guided wave modes
      allows the characterization of their separate contribution to the scattered field
      and the evaluation of mode conversion phenomena. The effectiveness of these
      methods is demonstrated through their application to detection of a delamination
      in a composite plate and detection of a crack emanating from a hole.

PMID- 21190707
TI  - Baculovirus resistance in codling moth (Cydia pomonella L.) caused by early block
      of virus replication.
AB  - An up to 10,000-fold resistance against the biocontrol agent Cydia pomonella
      granulovirus (CpGV) was observed in field populations of codling moth, C.
      pomonella, in Europe. Following different experimental approaches, a modified
      peritrophic membrane, a modified midgut receptor, or a change of the innate
      immune response could be excluded as possible resistance mechanisms. When CpGV
      replication was traced by quantitative PCR in different tissues of susceptible
      and resistant insects after oral and intra-hemocoelic infection, no virus
      replication could be detected in any of the tissues of resistant insects,
      suggesting a systemic block prior to viral DNA replication. This conclusion was
      corroborated by fluorescence microscopy using a modified CpGV (bacCpGV(hsp-eGFP))
      carrying enhanced green fluorescent gene (eGFP), which showed that infection in
      resistant insects did not spread. In conclusion, the different lines of evidence
      indicate that CpGV can enter but not replicate in the cells of resistant codling
      moth larvae.

PMID- 21190708
TI  - Fouling behavior of microstructured hollow fiber membranes in submerged and
      aerated filtrations.
AB  - The performance of microstructured hollow fiber membranes in submerged and
      aerated systems was investigated using colloidal silica as a model foulant. The
      microstructured fibers were compared to round fibers and to twisted
      microstructured fibers in flux-stepping experiments. The fouling resistances in
      the structured fibers were found to be higher than those of round fibers. This
      was attributed to stagnant zones in the grooves of the structured fibers. As the
      bubble sizes were larger than the size of the grooves of the structured fibers,
      it is possible that neither the bubbles nor the secondary flow caused by the
      bubbles can reach the bottom parts of the grooves. Twisting the structured fibers
      around their axes resulted in decreased fouling resistances. Large, cap-shaped
      bubbles and slugs were found to be the most effective in fouling removal, while
      small bubbles of sizes similar to the convolutions in the structured fiber did
      not cause an improvement in these fibers. Modules in a vertical orientation
      performed better than horizontal modules when coarse bubbling was used. For small
      bubbles, the difference between vertical and horizontal modules was not
      significant. When the structured and twisted fibers were compared to round fibers
      with respect to the permeate flowrate produced per fiber length instead of the
      actual flux through the convoluted membrane area, they showed lower fouling
      resistance than round fibers. This is because the enhancement in surface area is
      more than the increase in resistance caused by stagnant zones in the grooves of
      the structured fibers. From a practical point of view, although the
      microstructure does not promote further turbulence in submerged and aerated
      systems, it can still be possible to enhance productivity per module with the
      microstructured fibers due to their high surface area-to-volume ratio.

PMID- 21190709
TI  - Feasibility of a two-stage reduction/subsequent oxidation for treating
      Tetrabromobisphenol A in aqueous solutions.
AB  - A "two-stage reduction/subsequent oxidation" (T-SRO) process consists of Fe-Ag
      reduction and Fenton-like oxidation under ultrasound (US) radiation. Due to the
      refractory oxidation of brominated flame retardant, T-SRO was employed to remove
      Tetrabromobisphenol A (TBBPA) by the combination of first debromination and
      succeeding oxidation. It indicated that the T-SRO process resulted in a complete
      decrease in TBBPA concentration and a 99.2% decrease in BPA concentration. The T
      SRO process for the removal of TBBPA is much effective than Fenton-like oxidation
      of TBBPA alone. The result showed that US radiation improved the Fenton-like
      oxidation rate of BPA solutions. The addition of dissolved iron into the Fenton
      like oxidation system could accelerate the first 2 min reaction, but had little
      effect on the following process. The main intermediate products resulting from
      TBBPA reduction and BPA oxidation were identified by GC-MS and LC-MS/MS. On the
      basis of this analysis, reactions with *OH radical were identified as the major
      chemical pathways during BPA oxidation.

PMID- 21190710
TI  - Congener-based analysis of the weathering of PCB Aroclor 1242 in paper mill
      sludge.
AB  - Aroclor 1242 contains a high percentage of lightly chlorinated congeners, which
      makes it susceptible to congener profile alterations as a result of physical
      chemical environmental weathering by water washing, evaporation, and
      volatilization. The analysis of the variability of congener profiles in paper
      sludge samples using PCA, mixing models, and correlation (R(2)) analysis,
      provided an integrated description of the behavior of Aroclor 1242 after its
      release in the environment. The results showed that the total PCB concentration
      decreased as the sample experienced weathering, with the congener profile of
      Aroclor 1242 shifting towards resembling heavier Aroclors as lighter congeners
      were lost. Mixing model analysis confirmed that a sample containing weathered
      Aroclor 1242 could easily be misidentified by laboratories as containing a mix of
      heavier Aroclors. The R(2) analysis showed that the profile of the congeners
      within a homologue group remained the same after weathering. This analysis showed
      that congeners that belong to the same level of chlorination behave similarly in
      such a manner that retains their overall profile when exposed to physical
      weathering.

PMID- 21190711
TI  - Use of hematological and plasma biochemical parameters to assess the chronic
      effects of a fungicide propiconazole on a freshwater teleost.
AB  - Blood is an indicator of physiological condition of an animal. Therefore, the
      chronic effects of propiconazole, a triazole fungicide present in aquatic
      environment, on hematology of rainbow trout were investigated in this study. Fish
      were exposed at various concentrations of PCZ (0.2, 50 and 500 MUg L(-1)) for 7,
      20 and 30 d. Multiple biomarkers were measured, including hematological indices
      (hemoglobin concentration, red blood cells count, hematocrit, leukocyte count,
      mean erythrocyte hemoglobin, mean erythrocyte volume and mean color
      concentration) and plasma biochemical parameters (ammonia, glucose, total
      proteins, creatine kinase, lactate dehydrogenase, alanine aminotransferase and
      aspartate aminotransferase). Through principal component analysis and integrated
      biomarker response assessment, influence extent induced by PCZ-stress of each
      test group was distinguished. Additional, all parameters measured in this study
      displayed different dependent patterns to PCZ concentrations and exposure time by
      two-way ANOVA. The results of this study indicate that chronic exposure of PCZ
      has altered multiple physiological indices in fish hematology and CK activity may
      be an early biomarker of PCZ toxicity; however, before these parameters are used
      as special biomarkers for monitoring residual PCZ in aquatic environment, more
      detailed experiments in laboratory need to be performed in the future.

PMID- 21190712
TI  - Development of a combined isotopic and mass-balance approach to determine
      dissolved organic carbon sources in eutrophic reservoirs.
AB  - A combined mass-balance and stable isotope approach was set up to identify and
      quantify dissolved organic carbon (DOC) sources in a DOC-rich (9mgL(-1))
      eutrophic reservoir located in Western France and used for drinking water supply
      (so-called Rophemel reservoir). The mass-balance approach consisted in measuring
      the flux of allochthonous DOC on a daily basis, and in comparing it with the
      effective (measured) DOC concentration of the reservoir. The isotopic approach
      consisted, for its part, in measuring the carbon isotope ratios (delta(13)C
      values) of both allochthonous and autochthonous DOC sources, and comparing these
      values with the delta(13)C values of the reservoir DOC. Results from both
      approaches were consistent pointing out for a DOC of 100% allochthonous origin.
      In particular, the delta(13)C values of the DOC recovered in the reservoir (
      28.5+/-0.20/00; n=22) during the algal bloom season (May-September) showed no
      trace of an autochthonous contribution (delta(13)C in algae=-30.1+/-0.30/00; n=2)
      being indistinguishable from the delta(13)C values of allochthonous DOC from
      inflowing rivers (-28.6+/-0.10/00; n=8). These results demonstrate that
      eutrophication is not responsible for the high DOC concentrations observed in the
      Rophemel reservoir and that limiting eutrophication of this reservoir will not
      reduce the potential formation of disinfection by-products during water
      treatment. The methodology developed in this study based on a complementary
      isotopic and mass-balance approach provides a powerful tool, suitable to identify
      and quantify DOC sources in eutrophic, DOC-contaminated reservoirs.

PMID- 21190713
TI  - Elimination of persistent organic pollutants from fish oil with solid adsorbents.
AB  - Fish oils are one of the main sources of omega-3 fatty acids in animal and human
      diet. However, they can contain high concentrations of persistent organic
      pollutants due to their lipophilic properties. The aim of this study is the
      reduction of persistent organic pollutants in fish oil using silicon-based and
      carbon-based solid adsorbents. A wide screening study with different commercially
      available adsorbents was carried out, in order to determine their capacity of
      pollutant removal from fish oil. Moreover, adsorption conditions were evaluated
      and optimized with using an experimental design and adjustment of the
      experimental results to response surfaces, obtaining removals rates of more than
      99% of PCDD/Fs, 81% of dioxin-like PCBs, 70% of HCB, 41% of DDTs, 16% of marker
      PCBs and 10% of PBDEs. Finally, fish oil fatty acids were analyzed before and
      after the treatment with solid adsorbents, confirming that it did not affect its
      nutritive properties.

PMID- 21190714
TI  - Physiological responses of glyphosate-resistant and glyphosate-sensitive soybean
      to aminomethylphosphonic acid, a metabolite of glyphosate.
AB  - Aminomethylphosphonic acid (AMPA) is formed in glyphosate-treated glyphosate
      resistant (GR) and glyphosate-sensitive (GS) soybean [Glycine max (L.) Merr.]
      plants and is known to cause yellowing in soybean. Although, AMPA is less
      phytotoxic than glyphosate, its mode of action is different from that of
      glyphosate and is still unknown. Greenhouse studies were conducted at Stoneville,
      MS to determine the effects of AMPA on plant growth, chlorophyll content,
      photosynthesis, nodulation, nitrogenase activity, nitrate reductase activity, and
      shoot nitrogen content in GR and GS soybeans. AMPA was applied to one- to two
      trifoliolate leaf stage soybeans at 0.1 and 1.0 kg ha(-1), representing a
      scenario of 10% and 100% degradation of glyphosate (1.0 kg ae ha(-1) use rate) to
      AMPA, respectively. Overall, AMPA effects were more pronounced at 1.0 kg ha(-1)
      than at 0.1 kg ha(-1) rate. Visual plant injury (18-27%) was observed on young
      leaves within 3d after treatment (DAT) with AMPA at the higher rate regardless of
      soybean type. AMPA injury peaked to 46-49% at 14 DAT and decreased to 17-18% by
      28 DAT, in both soybean types. AMPA reduced the chlorophyll content by 37%, 48%,
      66%, and 23% in GR soybean, and 17%, 48%, 57%, and 22% in GS soybean at 3, 7, 14,
      and 28 DAT, respectively. AMPA reduced the photosynthesis rate by 65%, 85%, and
      77% in GR soybean and 59%, 88%, and 69% in GS soybean at 3, 7, and 14 DAT,
      respectively, compared to non-treated plants. Similarly, AMPA reduced stomatal
      conductance to water vapor and transpiration rates at 3, 7, and 14 DAT compared
      to non-treated plants in both soybean types. Photosynthesis rate, stomatal
      conductance, and transpiration rate recovered to the levels of non-treated plants
      by 28 DAT. Plant height and shoot dry weight at 28 DAT; nodulation, nitrogenase
      activity at 10 DAT, and nitrate reductase activity at 3 and 14 DAT were
      unaffected by AMPA. AMPA reduced root respiration and shoot nitrogen content at
      10 DAT. These results suggest that a foliar application of AMPA could indirectly
      reduce photosynthesis through decreased chlorophyll content in GR and GS soybean
      up to 14 DAT, but affected plants can recover to normal growth by 28 DAT.

PMID- 21190715
TI  - Assessing the health risk of reuse of bottom ash in road paving.
AB  - Although the reuse of bottom ash has been favored gradually, reflected on
      regulations and researches, the associated risk is still an issue of great
      concern. This study quantified the health risks from multimedia transport and
      multi-pathway exposure to the concerned chemicals as a result of reusing bottom
      ash in road paving with consideration of various application scenarios. In
      particular, the using duration of the pavement was taken into consideration
      because movement of chemicals in the soils and groundwater would affect the
      subsequent exposure and risk. By using soil and groundwater transport modeling
      linked to food chain exposure assessment and incorporating the Monte Carlo
      method, the study identified Cr as the crucial toxicant and ingestion of drinking
      water and vegetables as the key exposure pathways. Furthermore, control of the
      using duration of road pavement is an essential factor of management and
      regulations to minimize the leaching of the hazardous constituents into the
      groundwater and subsequent contamination of food chain.

PMID- 21190716
TI  - Insecticide residues in cotton soils of Burkina Faso and effects of insecticides
      on fluctuating asymmetry in honey bees (Apis mellifera Linnaeus).
AB  - Four insecticides (acetamiprid, cypermethrin, endosulfan and profenofos) are used
      quarterly in the cotton-growing areas of Burkina Faso, West Africa. These
      insecticides were investigated in soils collected from traditionally cultivated
      and new cotton areas. Also, the effects of insecticide exposure on the
      developmental instability of honey bees, Apis mellifera, were explored. In soil
      samples collected three months after insecticide treatments, endosulfan and
      profenofos concentrations varied in the range of 10-30 MUg kg(-1) in the
      traditionally cultivated zones and 10-80 MUg kg(-1) in the new cotton zones,
      indicating a pollution of agricultural lands. However, only profenofos
      concentrations were significantly higher in the new cotton zone than the
      traditionally cultivated zones. In addition, the index of fluctuating asymmetry,
      FA1, in the length of second tarsus (L(HW)) was increased for bees when exposed
      to pesticide treated cotton fields for 82d, and their FA levels were
      significantly higher than those in the control colony in an orchard. The other
      studied traits of bees exposed to insecticides were not significantly different
      from controls. Our results indicate that FA may be considered as a biomarker
      reflecting the stress induced by insecticide treatments. However, the
      relationship between FA and stressors needs further investigations.

PMID- 21190717
TI  - Fluorinated alkyl compounds including long chain carboxylic acids in wild bird
      livers from Japan.
AB  - A wide range of fluorinated alkyl compounds (FACs) has been reported in wildlife
      in various locations in the world. However, such information regarding Japanese
      wildlife is rarely found. In the present study, we investigated the occurrence of
      21 FACs, including perfluorinated alkyl sulfonates (PFASs), perfluorinated
      carboxylates (PFCAs), and fluorotelomer acids, in the livers of 10 wild bird
      species from two regions in northern Japan. To avoid interferences, FACs were
      quantified by a recently developed method using acetonitrile and solid-phase
      extraction followed by an ion exchange HPLC column separation. Apart from
      perfluorooctane sulfonate (PFOS), which was found at the highest levels of all
      the compounds detected, several long chain perfluorinated carboxylates (PFCAs)
      from C8 to C16, particularly perfluorotetradecanoic acid (PFTeDA) and
      perfluorohexadecanoic acid (PFHxDA), were detected for the first time.
      Additionally, 7:3 FTCA, a fluorotelomer acid, was also detected in most swan
      livers from Miyagi prefecture and all the birds from Tochigi prefecture. However,
      none of the sulfonamides and unsaturated telomer acids were detected in any
      species. Swans seem to be the least exposed wild birds to FACs among the
      investigated birds, signifying that feeding habits may reflect FAC accumulation
      in wild birds. The highest total concentration of detected FACs was 405ngg(-1)wet
      wt., which was found in a Japanese sparrowhawk, indicating that the top predatory
      wild birds can accumulate several long chain carboxylic acids. However, the
      current FAC concentrations found in livers may suggest that these compounds alone
      would not cause a severe toxic effect in these species.

PMID- 21190718
TI  - Influence of soil properties on heavy metal sequestration by biochar amendment:
      2. Copper desorption isotherms.
AB  - Contaminant desorption constrains the long-term effectiveness of remediation
      technologies, and is strongly influenced by dynamic non-equilibrium states of
      environmental and biological media. Information is currently lacking in the
      influence of biochar and activated carbon amendments on desorption of heavy metal
      contaminants from soil components. In this study, copper sorption-desorption
      isotherms were obtained for clay-rich, alkaline San Joaquin soil with significant
      heavy metal sorption capacity, and eroded, acidic Norfolk sandy loam soil having
      low capacity to retain copper. Acidic pecan shell-derived activated carbon and
      basic broiler litter biochar were employed in desorption experiments designed to
      address both leaching by rainfall and toxicity characteristics. For desorption in
      synthetic rain water, broiler litter biochar amendment diminished sorption
      desorption hysteresis. In acetate buffer (pH 4.9), significant copper leaching
      was observed, unless acidic activated carbon (pH(pzc)=3.07) was present. Trends
      observed in soluble phosphorus and zinc concentrations for sorption and
      desorption equilibria suggested acid dissolution of particulate phases that can
      result in a concurrent release of copper and other sorbed elements. In contrast,
      sulfur and potassium became depleted as a result of supernatant replacements only
      when amended carbon (broiler litter biochar) or soil (San Joaquin) contained
      appreciable amounts. A positive correlation was observed between the equilibrium
      aluminum concentration and initial copper concentration in soils amended with
      acidic activated carbon but not basic biochar, suggesting the importance of
      cation exchange mechanism, while dissolution of aluminum oxides cannot be ruled
      out.

PMID- 21190719
TI  - Transfer of elements relevant to radioactive waste from soil to five boreal plant
      species.
AB  - In long-term safety assessment models for radioactive waste disposal, uptake of
      radionuclides by plants is an important process with possible adverse effects in
      ecosystems. Cobalt-60, (59,63)Ni, (93)Mo, and (210)Pb are examples of long-living
      radionuclides present in nuclear waste. The soil-to-plant transfer of stable
      cobalt, nickel, molybdenum and lead and their distribution across plant parts
      were investigated in blueberry (Vaccinium myrtillus), May lily (Maianthemum
      bifolium), narrow buckler fern (Dryopteris carthusiana), rowan (Sorbus aucuparia)
      and Norway spruce (Picea abies) at two boreal forest sites in Eastern Finland.
      The concentrations of all of the studied elements were higher in roots than in
      above-ground plant parts showing that different concentration ratios (CR values)
      are needed for modelling the transfer to roots and stems/leaves. Some significant
      differences in CR values were found in comparisons of different plant species and
      of the same species grown at different sites. However, large within-species
      variation suggests that it is not justified to use different CR values for
      modelling soil-to-plant transfer of these elements in the different boreal forest
      plant species.

PMID- 21190720
TI  - Differential expression of Yes-associated protein is correlated with expression
      of cell cycle markers and pathologic TNM staging in non-small-cell lung
      carcinoma.
AB  - Yes-associated protein, a downstream effector of the Hippo signaling pathway, has
      been linked to progression of non-small-cell lung carcinoma. The aim of this
      study was to investigate expression of Yes-associated protein in lung
      adenocarcinoma and squamous cell carcinoma. Associations of Yes-associated
      protein expression with clinicopathologic parameters, expression of cell cycle
      specific markers, and epidermal growth factor receptor gene amplification were
      also analyzed. In a univariate analysis of the 66 adenocarcinomas, high nuclear
      expression of Yes-associated protein was significantly correlated with expression
      of cyclin A and mitogen-activated protein kinase. Multivariate analysis,
      including age and sex, showed that cyclin A expression was independently
      correlated with nuclear expression of Yes-associated protein in adenocarcinomas.
      Furthermore, high nuclear expression of Yes-associated protein was also a
      significant predictor of epidermal growth factor receptor gene amplification for
      adenocarcinoma. For the 102 squamous cell carcinomas, univariate analysis
      revealed that high cytoplasmic expression of Yes-associated protein was
      correlated with the low pathologic TNM staging (stage I) and histologic grading.
      Multivariate analysis, including age and sex, showed that cytoplasmic expression
      of Yes-associated protein was an independent predictor of low pathologic TNM
      staging. These results indicate that nuclear overexpression of Yes-associated
      protein contributes to pulmonary adenocarcinoma growth and that high cytoplasmic
      expression of Yes-associated protein is an independent predictor of low
      pathologic TNM staging and histologic grading. The differential effects of Yes
      associated protein expression patterns in adenocarcinomas and squamous cell
      carcinomas suggest that Yes-associated protein may play important roles in
      different pathways in distinct tumor subtypes. These observations may, therefore,
      lead to new perspectives on therapeutic targeting of these tumor types.

PMID- 21190721
TI  - Overexpression of Cullin1 is associated with poor prognosis of patients with
      gastric cancer.
AB  - Cullin1 (Cul1) is a scaffold protein of the ubiquitin E3 ligase
      Skp1/Cullin1/Rbx1/F-box protein complex, which ubiquitinates a broad range of
      proteins involved in cell-cycle progression, signal transduction, and
      transcription. To investigate the role of Cullin1 in the development of gastric
      cancer, we examined the expression of Cullin1 in primary gastric cancer tissues
      and analyzed the correlation between Cullin1 expression and clinicopathologic
      variables and patients survival. We constructed a tissue microarray that includes
      792 primary gastric cancer tissues and evaluated the Cullin1 expression by
      immunohistochemistry in the tumor biopsies. We also studied the role of Cullin1
      in gastric cancer cell proliferation and adhesion by performing sulforhodamine B
      cell proliferation assay and cell attachment assay. The Cullin1 overexpression
      was significantly correlated with gastric cancer TNM stage (P = .011), depth of
      invasion (P = .035, comparing T1-T3 versus T4), and lymph node metastasis (P =
      .036). Furthermore, we showed a strong correlation between high Cullin1
      expression and worse overall and 3-year survival rates in gastric cancer patients
      (P = .042 and P = .026, respectively). Cox regression analysis revealed that
      Cullin1 expression was an independent prognostic factor to predict 3-year patient
      outcome in gastric cancer (P = .028). Finally, we found that Cullin1 knockdown
      inhibits cell growth by up-regulating p27 expression and decreases cell adhesion
      ability by suppressing the expression of Src family kinases and focal adhesion
      kinase. Our data indicated that Cullin1 may be an important marker for human
      gastric cancer lymph node metastasis and prognosis.

PMID- 21190722
TI  - Proposed histopathologic grading system derived from a study of KIT and CK19
      expression in pancreatic endocrine neoplasm.
AB  - Predicting the biologic behavior of pancreatic endocrine neoplasm in the absence
      of local invasion or metastasis is difficult. We recently proposed an
      immunohistochemical classification system based on a combination of KIT and CK19
      expression: low risk (KIT-/CK19-), intermediate risk (KIT-/CK19+), and high risk
      (KIT+/CK19+). In the current study, we sought histopathologic features that
      correlated with the immunohistochemical categories and that could be used in
      predicting tumor behavior. We assessed histologic findings of 97 pancreatic
      endocrine neoplasm that had been classified into 3 risk groups based on KIT/CK19
      expression. Clinicopathologic associations with prognosis were evaluated using
      Cox proportional hazards regression models. Tumor size, mitoses, infiltrative
      border, extrapancreatic extension, perineural invasion, and presence of amyloid
      were significantly different among the 3 risk groups, and tumor necrosis
      approached statistical significance as well (P = .089). A scoring system using
      mitoses, necrosis, and tumor border was developed as follows: mitosis: 0 (0/50
      high-power field), 1 (1-3/50 high-power field), and 2 (>=4/50 high-power field);
      necrosis: 0 (absent) and 1 (present); tumor border: 0 (noninfiltrating) and 1
      (infiltrating), giving a possible histology score of 0 to 4. Although there was
      an overall difference in disease-specific survival among the 4 histology scores
      (P < .001), there was not a statistically significant difference between patients
      with scores of 0 and 1 or between patients with scores of 3 and 4. Therefore, a 3
      tied grading system was developed by combining score 0 and 1 tumors as grade 1,
      score 2 tumors as grade 2, and score 3 and 4 tumors as grade 3. There was a
      significant difference in survival, tumor metastasis, tumor recurrence, and
      functioning status among the 3 grades. By analyzing histopathologic features in
      KIT/CK19 risk groups, we developed a 3-tiered histopathologic grading system
      using reproducible parameters (mitoses, tumor necrosis, and infiltrative border)
      that are easy to apply in practice.

PMID- 21190723
TI  - Preoperative radiotherapy modulates ezrin expression and its value as a
      predictive marker in patients with rectal cancer.
AB  - The purpose of this study was to assess the value of ezrin expression as a
      predictor of disease outcome in rectal cancer treated by preoperative radio- or
      chemoradiotherapy. Operative samples from 176 rectal cancer patients and 76
      diagnostic preoperative biopsies from the same cohort were analyzed for ezrin
      expression using immunohistochemistry. The patients had received short- (n = 76)
      or long-course radiotherapy with (n = 36) or without chemotherapy (n = 10) or no
      treatment preoperatively (n = 54). The direct effect of radiation on ezrin
      expression was studied in cultured cells by Western blot analysis. The biopsies
      and respective operative samples were significantly different (kappa = -0.010 for
      4-tier scoring and kappa = 0.028 for dichotomized scoring) in their ezrin
      expression. Most preoperative biopsies (61/76, 80%) had negative/weak ezrin
      expression compared with 56% (43/76) of the corresponding operative samples.
      After preoperative treatment, negative expression in the biopsies of 18 (82%) of
      22 patients turned positive, whereas positive expression in 6 (11%) of 54
      biopsies turned negative in the operative samples. In univariate analysis,
      disease-free survival and disease-specific survival were significantly longer (P
      = .027 and P = .002) when ezrin expression in the preoperative biopsy was
      negative/weak compared with moderate/strong expression. Such prognostic
      association was lost in the radiated operative specimens. In multivariate
      regression model, ezrin was not a predictor of disease-free survival. No direct
      effect of radiation on ezrin expression was seen in vitro. In conclusion,
      radiotherapy increases ezrin expression in rectal cancer. In pretreatment
      biopsies, negative/weak ezrin expression correlates with favorable disease
      outcome, suggesting that ezrin expression modulates tumor aggressiveness and/or
      response to treatment.

PMID- 21190725
TI  - Micrometastases in para-aortic lymph nodes in advanced cervical cancer patients-
      are a true predictor of recurrence at this level?

PMID- 21190726
TI  - Skin scar recurrence following removal of a sentinel lymph node containing a
      solitary micrometastasis of squamous cell vulval cancer.

PMID- 21190724
TI  - Comparative expression analysis of the phosphocreatine circuit in extant
      primates: Implications for human brain evolution.
AB  - While the hominid fossil record clearly shows that brain size has rapidly
      expanded over the last ~2.5 M.yr. the forces driving this change remain unclear.
      One popular hypothesis proposes that metabolic adaptations in response to dietary
      shifts supported greater encephalization in humans. An increase in meat
      consumption distinguishes the human diet from that of other great apes. Creatine,
      an essential metabolite for energy homeostasis in muscle and brain tissue, is
      abundant in meat and was likely ingested in higher quantities during human
      origins. Five phosphocreatine circuit proteins help regulate creatine utilization
      within energy demanding cells. We compared the expression of all five
      phosphocreatine circuit genes in cerebral cortex, cerebellum, and skeletal muscle
      tissue for humans, chimpanzees, and rhesus macaques. Strikingly, SLC6A8 and CKB
      transcript levels are higher in the human brain, which should increase energy
      availability and turnover compared to non-human primates. Combined with other
      well-documented differences between humans and non-human primates, this
      allocation of energy to the cerebral cortex and cerebellum may be important in
      supporting the increased metabolic demands of the human brain.

PMID- 21190728
TI  - Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to
      foods, drugs, and insects in 2010.
AB  - This review highlights some of the research advances in anaphylaxis;
      hypersensitivity reactions to foods, drugs, and insects; and allergic skin
      disease that were reported in the Journal in 2010. Key epidemiologic observations
      include an apparent increase in peanut allergy, with more than 1% of children
      affected, and increasing evidence that early food allergen exposure, rather than
      avoidance, might improve allergy outcomes. Advances in food allergy diagnosis
      include improved insights into prognosis and estimation of severity through
      component-resolved diagnostics and characterization of IgE binding to specific
      epitopes. Regarding treatment, oral and epicutaneous immunotherapy show promise.
      Studies of drug allergies show insights into pathophysiology, and studies on
      insect hypersensitivity reveal improved diagnostic methods. Genetic and
      functional studies have revealed the important role of epidermal differentiation
      products in the pathogenesis of atopic dermatitis. Cross-talk between the atopic
      immune response with the innate immune response have also been found to
      predispose to infection in patients with atopic dermatitis. New therapeutic
      approaches to control chronic urticaria have also been identified during the past
      year.

PMID- 21190729
TI  - Factors affecting nuclear maturation, cleavage and embryo development of
      vitrified bovine cumulus-oocyte complexes.
AB  - The objective was to investigate the effects of cryodevice, vitrification
      solutions, and equilibration time on in vitro maturation, cleavage, and embryo
      development of vitrified bovine oocytes. In Experiment 1, the nuclear maturation
      (MII) rate of immature bovine COCs vitrified was compared between two
      equilibration times (0 vs 10 min) in vitrification solution 1 (VS1) and two
      cryodevices (cryotop vs 0.25 mL straw). The MII rate was higher in the non
      vitrified control group than in vitrified groups (61 vs 16%, P < 0.0001).
      Equilibration time did not affect MII rate (P = 0.964); however, the MII rate was
      higher for COCs vitrified on cryotops than in straws (23 vs 9%, P = 0.007). In
      Experiment 2, bovine COCs were vitrified on cryotops using two equilibration
      times (0 vs 5 min) in VS1 and two kinds of vitrification solutions (freshly
      prepared vs frozen). Cleavage and blastocyst rates were higher (P < 0.0001) in
      the non-vitrified control group than vitrified groups (cleavage rate 93 vs 42%
      and blastocysts rate 31 vs 0.4%). Cleavage rate of COCs vitrified using frozen
      solutions with 5 min equilibration was higher (P = 0.05) than other treatment
      groups. However, blastocyst rate did not differ (P = 0.993) among treatment
      groups. In conclusion, cryotop was a better cryodevice than 0.25 mL straw for
      vitrification of bovine COCs. Furthermore, 5 min equilibration in VS1 improved
      cleavage. Compared with control, the vitrification procedure per se damaged
      bovine COCs, resulting in poor nuclear maturation and embryo development.
      However, vitrification did not immediately kill oocytes, as the cleavage rate was
      acceptable.

PMID- 21190730
TI  - Incidence, structure and morphological classification of abnormal sperm in the
      emu (Dromaius novaehollandiae).
AB  - Little detailed information is currently available on the incidence and
      morphological characteristics of abnormal sperm in the emu (Dromaius
      novaehollandiae) and of ratites in general. This situation is further compounded
      by the lack of a uniform system for the morphological classification of avian
      sperm defects. Considering the important role that sperm morphology plays in the
      assessment of semen quality, a detailed description of avian sperm defects is of
      paramount importance. Based on morphological data provided by light and electron
      microscopy, a mean of 17.3% abnormal sperm was recorded in semen samples
      collected from the distal deferent duct of four adult emus during the middle of
      the breeding season. Four categories of defects were identified. Head defects
      (57.2% of total defects) consisted of bent heads, macrocephalic heads, round
      heads and acephalic sperm. Zones of incomplete chromatin condensation and
      retained cytoplasmic droplets appeared to be implicated in head bending, while
      giant heads were often associated with multiple tails. Acephalic sperm revealed a
      complete tail devoid of a head which was replaced by a small spherical structure.
      Tail defects (22.6% of total defects) were subdivided into neck/midpiece defects
      and principal piece defects. In the neck/midpiece region disjointed sperm were
      the exclusive defect noted and were characterized by the complete separation of
      the head and midpiece in the neck region but within the confines of the
      plasmalemma. Defects observed in the principal piece were subdivided into short
      tails, coiled tails and multiple tails. No conclusive evidence was obtained that
      tail coiling represented the 'Dag' defect. Biflagellate sperm were the most
      common form of multiple tails, demonstrating two complete tails with all the
      normal structural elements. Cytoplasmic droplets (13.9% of total defects) were
      classified as a separate defect. The location and eccentric positioning of
      retained cytoplasmic droplets was similar to that described in ostrich sperm
      although the composition of the droplets differed markedly between the two
      species. A small percentage of sperm (6.3% of total sperm defects) displayed
      multiple abnormalities. Based on these findings we propose a morphological
      classification for abnormal ratite sperm identifying head and tail defects, with
      additional categories for cytoplasmic droplets and multiple defects. Each
      category is further subdivided to reflect a range of specific defects within the
      category. It is envisaged that additional defects will be added to each category
      or that new categories may be added as future studies on the detailed morphology
      of avian sperm defects are completed.

PMID- 21190732
TI  - CML: Defining the efficacy of targeted therapy with the TARGET system.

PMID- 21190731
TI  - Chondrogenic differentiation of human bone marrow mesenchymal stem cells on
      polyhydroxyalkanoate (PHA) scaffolds coated with PHA granule binding protein PhaP
      fused with RGD peptide.
AB  - Hydrophobic polyhydroxyalkanoate (PHA) scaffolds made of a copolyester of 3
      hydroxybutyrate-co-hydroxyhexanoate (PHBHHx) were coated with a fusion protein
      PHA granule binding protein PhaP fused with RGD peptide (PhaP-RGD). Human bone
      marrow mesenchymal stem cells (hBMSCs) were inoculated on/in the scaffolds for
      formation of articular cartilages derived from chondrogenic differentiation of
      hBMSCs for cartilage tissue engineering. PhaP-RGD coating led to more homogeneous
      spread of cells, better cell adhesion, proliferation and chondrogenic
      differentiation in the scaffolds compared with those of PhaP coated or uncoated
      scaffolds immerging in serum minus chondrogenic induction medium. In addition,
      more extracellular matrices were produced by the differentiated cells over a
      period of 14 days on/in the PhaP-RGD coated scaffolds evidenced by scanning
      electron microscopy imaging, enhanced expression of chondrocyte specific genes
      including SOX-9, aggrecan and type II collagen, suggesting the positive effect of
      RGD on extracellular matrix production. Furthermore, cartilage-specific
      extracellular substances sulphated glycosaminoglycans (sGAG) and total collagen
      content found on/in the PhaP-RGD coated scaffolds were significantly more
      compared with that produced by the control and PhaP only coated scaffolds.
      Homogeneously distributed chondrocytes-like cells forming cartilage-like matrices
      were observed on/in the PhaP-RGD coated scaffolds after 3 weeks. The results
      suggested that PhaP-RGD coated PHBHHx scaffold promoted chondrogenic
      differentiation of hBMSCs and could support cartilage tissue engineering.

PMID- 21190733
TI  - Subcellular Cd distribution and its correlation with antioxidant enzymatic
      activities in wheat (Triticum aestivum) roots.
AB  - The subcellular partitioning of Cd in wheat root was obtained by differential
      centrifugation of root homogenates to quantify the amounts of Cd associated with
      five operationally defined subcellular fractions, namely Cd-rich granule (MRG),
      cellular debris, organelles, heat-denatured protein (HDP), and heat-stable
      protein (HSP). Their correlations were investigated with the changes in
      antioxidant enzymatic activities under Cd stress (0.01-9.68 MUM) for 72 h. The
      results showed that the relative Cd distribution in detoxified fractions
      (MRG+HSP) was decreased with increasing [Cd], but in metal-sensitive fractions
      (HDP+organelles) was increased. Consequently, the content of superoxide dismutase
      (SOD) and catalase (CAT) was decreased. Additionally, an increase of the total
      antioxidant capacity (A-TOC) and a slight decrease of malondialdehyde (MDA) were
      also observed. Interestingly, the relative root elongation (RRL) and CAT were
      significantly correlated with the Cd-sensitive fractions. These results suggest
      that the Cd toxicity to wheat roots strongly depends on the subcellular Cd
      distribution.

PMID- 21190734
TI  - Avian CD154 enhances humoral and cellular immune responses induced by an
      adenovirus vector-based vaccine in chickens.
AB  - Recombinant adenoviral vectors have emerged as an attractive system for
      veterinary vaccines development. However, for poultry vaccination a very
      important criterion for an ideal vaccine is its low cost. The objective of this
      study was to test the ability of chicken CD154 to enhance the immunogenicity of
      an adenoviral vector-based vaccine against avian influenza virus in order to
      reduce the amount of antigen required to induce an effective immune response in
      avian. Chickens were vaccinated with three different doses of adenoviral vectors
      encoding either HA (AdHA), or HA fused to extracellular domain chicken's CD154
      (AdHACD). Hemagglutination inhibition (HI) assay and relative quantification of
      IFN-gamma showed that the adenoviral vector encoding for the chimeric antigen is
      able to elicit an improved humoral and cellular immune response, which
      demonstrated that CD154 can be used as a molecular adjuvant allowing to reduce in
      about 50-fold the amount of adenoviral vector vaccine required to induce an
      effective immune response.

PMID- 21190735
TI  - "Show me your impact": evaluating transitional justice in contested spaces.
AB  - This paper discusses some of the most significant challenges and opportunities
      for evaluating the effects of programs in support of transitional justice - the
      field that addresses how post-conflict or post authoritarian societies deal with
      legacies of wide spread human rights violations. The discussion is empirically
      grounded in a case study that assesses the efforts of the International
      Development Research Centre (IDRC) and one of its Guatemalan partners to evaluate
      the effects of a museum exposition that is attempting to recast historic memory
      and challenge racist attitudes in post-conflict Guatemala. The paper argues that
      despite the increasing trend to fund transitional justice programs, many
      international aid donors are stuck in traditional and arguably orthodox paradigms
      of program evaluation. This is having a negative effect not only upon the
      administration of aid but also upon how transitional justice research is
      perceived and valued by local populations. The case study experience indicates
      that there is no perfect evaluation model or approach for evaluating transitional
      justice programming - only choices to be made by commissioners of evaluation,
      evaluators, and those being evaluated. These are profoundly influenced by the
      extreme politics and moral values that define transitional justice settings as
      contested spaces in which calls to remember the tragic past must be balanced with
      aspirations to re-build a hopeful future.

PMID- 21190736
TI  - The non-conventional MHC class I MR1 molecule controls infection by Klebsiella
      pneumoniae in mice.
AB  - As opposed to the well established role of MHC-linked, polymorphic, class I (MHC
      I) genes in adaptive immunity, a universal role for non-conventional MHC-I is
      unknown, thus requiring a case-by-case study. The MHC unlinked, monomorphic, but
      beta2microglobulin (beta2m)-associated "MHC class I related" MR1 molecule
      interacts with a semi-invariant TCR. The pathophysiology of this interaction or
      more importantly of this peculiar MHC-I remains mostly unknown. Recently it was
      shown that beta2m deficient mice were more susceptible to infection by Klebsiella
      pneumoniae, a widely spread Gram-negative bacteria that causes diverse and often
      severe ailments in man. Here we demonstrate, using both an in vivo imaging system
      and survival tests, the increased susceptibility to K. pneumoniae (but not to
      several other Gram negative bacteria) of MR1 deficient mice. This is accompanied
      by a consequent change in body temperature and systemic cytokine profile. Hence
      MR1 controls K. pneumoniae infection in vivo.

PMID- 21190737
TI  - Evolution of the peripheral blood lymphocyte populations in multiparous rabbit
      does with two reproductive management rhythms.
AB  - The emergence of epizootic rabbit enteropathy is leading to changes in weaning
      protocols in commercial rabbitries. Traditional weaning protocols are being
      replaced with late weaning, beyond 35 days postpartum (dpp). The main objectives
      of this study were to compare the peripheral blood lymphocyte populations of
      multiparous rabbit does under two reproductive rhythms (insemination at 11 dpp
      and weaning at 28 dpp, insemination at 25 dpp and weaning at 42 dpp), and to
      assess the influence on those of kits. Samples of peripheral blood were taken in
      22 adult females and 44 of their kits at different critical times, and several
      lymphocytic populations were evaluated by flow cytometry. Additionally, the
      perirenal fat thickness of does was also measured at partum and weaning to
      observe if body condition correlates with lymphocyte populations. During whole
      lactation, counts of total, CD5(+), CD4(+) and CD8(+) lymphocytes of females were
      generally lower with weaning at 42 dpp compared to 28 dpp. Moreover, counts of
      total, B and CD5(+) lymphocytes in rabbit does weaned at 42 dpp correlated to
      their body condition (+0.60 to 0.82; P<0.05), contrary to that observed in rabbit
      does weaned at 28 dpp. Some correlations between lymphocyte counts in both groups
      of does and weaning rabbits were observed. At weaning, those young rabbits weaned
      at 42 dpp had a significantly lower number of CD4(+) lymphocytes than those
      weaned at 28 dpp (P<0.01). In conclusion, the 42 ddp rabbit does presented a
      lower number of total lymphocytes and lymphocytic subpopulations during lactation
      and at weaning, as well as lesser capacity of adjustment during the gestation
      lactation cycle.

PMID- 21190738
TI  - The role of physical and psychological variables in predicting the outcome of
      hospitalization in very old adults.
AB  - The aim of this study was to examine predictors of functional outcome in
      hospitalized geriatric patients with a focus on psychological variables, as these
      have been somewhat neglected in this population. A prospective study was
      conducted in aged-care wards in Melbourne, Australia. Consecutively admitted
      patients (n = 100, mean age 82 years) completed measures of health status,
      anxiety, depression, self-efficacy, personality and coping. Two months later data
      were collected with respect to three outcomes, namely overall functioning,
      ability to carry out activities of daily living as measured by the Barthel Index
      (BI), and quality of life (QoL), as measured by the assessment of quality of life
      (AQoL) instrument. Syndromal depression was highly prevalent (28%) and syndromal
      anxiety was less common (5% prevalence), but neither was predictive of functional
      outcome. The strongest predictor of outcome was physical health status on
      admission to hospital. The results suggest that in physically unwell, very old
      populations, physical health factors may be stronger predictors of functioning
      than psychological variables. The findings also highlight some difficulties in
      the use of psychological measures in old-old populations, and the need for more
      research that recognizes the oldest old as a distinct group.

PMID- 21190739
TI  - Studies on bacterial endotoxin and intestinal absorption function in patients
      with chronic heart failure.
AB  - BACKGROUND: Small intestinal function may be altered in decompensated chronic
      heart failure (CHF) and translocating LPS may contribute to systemic inflammation
      observed in CHF. METHODS: We measured intestinal permeability (melibiose and
      rhamnose), active (3-O-methyl-d-glucose (3-OMG)) and passive (d-xylose) carrier
      mediated absorption in 20 CHF patients (12 edematous and 8 non-edematous) and 8
      controls by saccharide absorption technique assessing urinary recovery of orally
      administered sugars. We additionally measured LPS concentrations in 42 patients
      with decompensated heart failure and after recompensation. RESULTS: CHF patients
      had a 54% reduction of active carrier-mediated intestinal transport compared to
      controls (p<0.0001). This reduction was strongest in edematous compared to non
      edematous patients and controls (recovery in urine: 13.2+/-2.0% vs. 20.8+/-2.4%
      vs. 36.0 +/- 3.7%, all p <= 0.05). Patients showed a 34% reduction of passive
      carrier-mediated transport, strongest in edematous patients (p=0.006). A greater
      impairment of active carrier-mediated transport remained significant after
      adjustment for non-mucosal factors in CHF (p=0.0004). Non carrier-mediated
      intestinal permeability was not altered. Data from 42 decompensated patients
      showed a decrease in LPS after recompensation (p=0.004). Edematous patients had
      highest blood concentrations of LPS, TNF and sTNF-R1 (p<0.04). CHF patients with
      abnormal LPS concentrations >0.50EU/mL (n=7) had the highest concentrations of
      TNF (7.0 +/- 1.6 vs. 3.1 +/- 0.3pg/mL, p<0.02), and sTNF-R1 (3499 +/- 52 vs.
      1599+/-219 pg/mL, p=0.02). CONCLUSION: Active carrier-mediated intestinal
      transport is reduced in decompensated CHF indicating epithelial dysfunction
      possibly as a consequence of intestinal ischemia. Higher LPS concentrations in
      edematous CHF relate to inflammation. LPS decreased after recompensation. This
      suggests a cause/effect relationship between edematous gut wall, epithelial
      dysfunction and translocating LPS.

PMID- 21190740
TI  - Comparison of adenosine magnetic resonance perfusion imaging with invasive
      coronary flow reserve and fractional flow reserve in patients with suspected
      coronary artery disease.

PMID- 21190741
TI  - HIV infection is not associated with echocardiographic signs of cardiomyopathy or
      pulmonary hypertension among pregnant Ugandan women.

PMID- 21190742
TI  - Monocyte trans-endothelial migration augments subsequent transmigratory activity
      with increased PECAM-1 and decreased VE-cadherin at endothelial junctions.
AB  - BACKGROUND: Although the importance of monocyte trans-endothelial migration in
      early atherogenesis is well recognized, it is unclear whether and how one
      transmigration event affects endothelium to facilitate subsequent ones. In this
      study, we tested the hypothesis that monocyte transmigration alters endothelial
      junctional organization to facilitate subsequent transmigration. METHODS AND
      RESULTS: When human monocytes were added twice at intervals of ~30 min to IL
      1beta-prestimulated human umbilical vein endothelial cells in vitro, significant
      augmentation of transmigration was observed at the second addition (~1.5-fold,
      analyzed from a total of 231 monocytes in 3 experiments). Endothelial surface
      expressions of two major junctional molecules, PECAM-1 and VE-cadherin, increased
      and decreased respectively, in response to monocyte addition, which could
      facilitate subsequent transmigration. To further investigate spatiotemporal
      dynamics of the increasing molecule, PECAM-1, we constructed a PECAM-1-GFP
      expression system and found that monocyte transmigration induced local
      accumulation of endothelial PECAM-1 around the transmigration spot, which was
      followed by transmigration of subsequent monocyte around the same location.
      Detailed analysis revealed that within the defined region around one
      transmigration event, 50% of later transmigrating monocytes used the same or
      similar location as the previous one (10 out of 20 transmigrating monocytes in 11
      experiments). CONCLUSIONS: These findings show that monocyte trans-endothelial
      migration alters endothelial junctional organization to a more monocyte-permeable
      state (increased PECAM-1 and decreased VE-cadherin), resulting in the augmented
      transmigratory activity at a later stage. This positive feedback mechanism is
      partially associated with monocyte transmigration-induced local accumulation of
      endothelial PECAM-1, which promotes transmigration of following monocytes at the
      same location.

PMID- 21190743
TI  - Poor outcome after recurrent acute myocardial infarction: a plea for optimal
      secondary prevention.

PMID- 21190744
TI  - Brain natriuretic peptide and tumour markers in the diagnosis of non-malignant
      pericardial effusion.

PMID- 21190745
TI  - Structure and process measures of quality of care in adult congenital heart
      disease patients: a pan-Canadian study.
AB  - BACKGROUND: There are more adults than children with congenital heart disease. Of
      over 96,000 ACHD patients in Canada, approximately 50% require ongoing expert
      care. In spite of published recommendations, data on the quality of care for ACHD
      patients are lacking. METHODS: Survey methodology targeted all Canadian Adult
      Congenital Heart (CACH) network affiliated ACHD centers. Clinics were asked to
      prospectively collect outpatient and procedural volumes for 2007. In 2008,
      centers were surveyed regarding infrastructure, staffing, patient volumes and
      waiting times. RESULTS: All 15 CACH network registered centers responded. The
      total number of patients followed in ACHD clinics was 21,879 (median per
      clinic=1132 (IQR: 585, 1816)). Of the total 80 adult and pediatric cardiologists
      affiliated to an ACHD clinic, only 27% had received formal ACHD training. Waiting
      times for non-urgent consultations were 4 +/- 2 months, and 4 +/- 3 months for
      percutaneous and surgical procedures. These were beyond Canadian recommended
      targets at 11 sites (73%) for non-urgent consultations, at 8 sites (53%) for
      percutaneous interventions and 13 sites (87%) for surgery. CONCLUSIONS: Of a
      minimum number of 96,000 ACHD patients in Canada, only 21,879 were being
      regularly followed in 2007. At most sites waiting times for ACHD services were
      beyond Canadian recommended targets. In spite of universal health care access,
      published guidelines for ACHD patient structure and process measures of health
      care quality are not being met.

PMID- 21190746
TI  - Ischemic strokes after ablation of typical atrial flutter.

PMID- 21190747
TI  - Tanshinone IIA prevents doxorubicin-induced cardiomyocyte apoptosis through Akt
      dependent pathway.
AB  - BACKGROUND: Doxorubicin, one of the original anthracyclines, remains among the
      most effective anticancer drugs ever developed. Clinical use of doxorubicin is,
      however, greatly limited by its serious adverse cardiac effects that may
      ultimately lead to cardiomyopathy and heart failure. Tanshinone IIA is the main
      effective component of Salvia miltiorrhiza known as 'Danshen' in traditional
      Chinese medicine for treating cardiovascular disorders. The objective of this
      study was set to evaluate the protective effect of tanshinone IIA on doxorubicin
      induced cardiomyocyte apoptosis, and to explore its intracellular mechanism(s).
      METHODS: Primary cultured neonatal rat cardiomyocytes were treated with the
      vehicle, doxorubicin (1 MUM), tanshinone IIA (0.1, 0.3, 1 and 3 MUM), or
      tanshinone IIA plus doxorubicin. RESULTS: We found that tanshinone IIA (1 and 3
      MUM) inhibited doxorubicin-induced reactive oxygen species generation, reduced
      the quantity of cleaved caspase-3 and cytosol cytochrome c, and increased BcL
      x(L) expression, resulting in protecting cardiomyocytes from doxorubicin-induced
      apoptosis. In addition, Akt phosphorylation was enhanced by tanshinone IIA
      treatment in cardiomyocytes. The wortmannin (100 nM), LY294002 (10 nM), and siRNA
      transfection for Akt significantly reduced tanshinone IIA-induced protective
      effect. CONCLUSIONS: These findings suggest that tanshinone IIA protects
      cardiomyocytes from doxorubicin-induced apoptosis in part through Akt-signaling
      pathways, which may potentially protect the heart from the severe toxicity of
      doxorubicin.

PMID- 21190748
TI  - Waste to bioproduct conversion with undefined mixed cultures: the carboxylate
      platform.
AB  - Our societies generate increasing volumes of organic wastes. Considering that we
      also need alternatives to oil, an opportunity exists to extract liquid fuels or
      even industrial solvents from these abundant wastes. Anaerobic undefined mixed
      cultures can handle the complexity and variability of organic wastes, which
      produces carboxylates that can be efficiently converted to useful bioproducts.
      However, to date, barriers, such as inefficient liquid product separation and
      persistence of methanogens, have prevented the production of bioproducts other
      than methane. Here, we discuss combinations of biological and chemical pathways
      that comprise the 'carboxylate platform', which is used to convert waste to
      bioproducts. To develop the carboxylate platform into an important system within
      biorefineries, we must understand the kinetic and thermodynamic possibilities of
      anaerobic pathways, understand the ecological principles underlying pathway
      alternatives, and develop superior separation technologies.

PMID- 21190749
TI  - Multifaceted microbes.

PMID- 21190750
TI  - Disclosure of individual genetic data to research participants: the debate
      reconsidered.
AB  - Despite extensive debate, there is no consensus on whether individual genetic
      data should be disclosed to research participants. The emergence of whole-genome
      sequencing methods is increasingly generating unequalled amounts of genetic data,
      making the need for a clear feedback policy even more urgent. In this debate two
      positions can be broadly discerned: a restrictive disclosure policy ('no feedback
      except life-saving data') and an intermediate policy of qualified disclosure
      ('feedback if the results meet certain conditions'). We explain both positions
      and present the principal underlying arguments. We suggest that the debate should
      no longer address whether genetic research results should be returned, but
      instead how best to make an appropriate selection and how to strike a balance
      between the possible benefits of disclosure and the harms of unduly hindering
      biomedical research.

PMID- 21190751
TI  - Targeting the insulin-like growth factor I receptor inhibits proliferation and
      VEGF production of non-small cell lung cancer cells and enhances paclitaxel
      mediated anti-tumor effect.
AB  - The effects of AVE1642, a human monoclonal antibody against IGF-IR, were examined
      in NSCLC cell lines in order to characterize its anti-proliferative and anti
      angiogenic activity as a single agent and in combination with chemotherapy.
      AVE1642 inhibited IGF-IR signaling and suppressed IGF-I-induced, serum-stimulated
      or autocrine-mediated proliferation of NSCLC cells in vitro. Furthermore, the
      combination of paclitaxel and AVE1642 resulted in a sequence-dependent increase
      in the inhibition of cell proliferation, compared to each agent alone, which was
      associated with a dose-dependent increase in phosphorylated IGF-IR and Akt.
      Moreover, inhibition of IGF-IR signaling by AVE1642 reduced IGF-I-induced VEGF
      production by NSCLC cells as well as the migratory capacity of HUVEC cells
      challenged with conditioned media from lung cancer cells previously exposed to
      IGF-I. The above results suggest that inhibition of IGF-IR signaling by AVE1642
      enhances the efficacy of chemotherapy and modulates VEGF and angiogenesis in
      NSCLC. These effects may have important clinical implications in the treatment of
      NSCLC.

PMID- 21190752
TI  - Animals and the invention of the Phanerozoic Earth system.
AB  - Animals do not just occupy the modern biosphere, they permeate its structure and
      define how it works. Their unique combination of organ-grade multicellularity,
      motility and heterotrophic habit makes them powerful geobiological agents,
      imposing myriad feedbacks on nutrient cycling, productivity and environment. Most
      significantly, animals have 'engineered' the biosphere over evolutionary time,
      forcing the diversification of, for example, phytoplankton, land plants, trophic
      structure, large body size, bioturbation, biomineralization and indeed the
      evolutionary process itself. This review surveys how animals contribute to the
      modern world and provides a basis for reconstructing ancient ecosystems. Earlier,
      less animal-influenced biospheres worked quite differently from the one currently
      occupied, with the Ediacaran-Cambrian radiation of organ-grade animals marking a
      fundamental shift in macroecological and macroevolutionary expression.

PMID- 21190753
TI  - Heme oxygenase-1 is involved in the cytokinin-induced alleviation of senescence
      in detached wheat leaves during dark incubation.
AB  - This study tested whether an inducible isoform of heme oxygenase (HO, EC
      1.14.99.3), HO-1, is involved in the cytokinin (CTK)-induced alleviation of
      senescence in detached wheat (Triticum aestivum L.) leaves during dark
      incubation. We discovered that exogenous supplement of 6-benzylaminopurine (6-BA)
      at 10 MUM for 48 h not only delayed the dark-induced loss of chlorophyll and
      protein contents in detached wheat leaves, but also significantly increased HO
      activity in a time-dependent manner. This induction reached a maximum within 3h
      of 6-BA supply, which was further confirmed by using semi-quantitative RT-PCR and
      protein gel blot analysis. Furthermore, the decreases in intracellular
      thiobarbituric acid reactive substances (TBARS) content, and the increases in the
      transcript level, total and isozymatic activities of some important antioxidant
      enzymes, such as catalase (CAT, EC 1.11.1.6), peroxidase (POD, EC 1.11.1.7),
      superoxide dismutase (SOD, EC 1.15.1.1), and ascorbate peroxidase (APX, EC
      1.11.1.11), were observed. Reversed responses of chlorophyll, protein and TBARS
      contents, HO activity, and the expression of above antioxidant enzymes were
      observed when zinc protoporphyrin-IX (ZnPPIX), a potent HO-1 inhibitor, was added
      together with 6-BA. In contrast, HO-1 inducer hemin could partially mimic the
      effects of 6-BA. Together, the results suggest that HO-1 might be involved in the
      CTK-induced alleviation of senescence and lipid peroxidation in detached wheat
      leaves.

PMID- 21190754
TI  - Increased rate of irritable bowel syndrome and functional gastrointestinal
      disorders after Clostridium difficile infection.

PMID- 21190755
TI  - Ethanol in pre-surgical hand rubs: concentration and duration of application for
      achieving European Norm EN 12791.
AB  - In Europe, ethanol is a common active agent in hand rub formulations and nowadays
      it is also recommended in guidelines for hand hygiene published by the Centers
      for Disease Control and Prevention and by the World Health Organization. However,
      data on the range of concentrations and durations of application providing a
      basis for passing the efficacy test of the European norm EN 12791 are still
      lacking. Therefore, the bactericidal efficacy of rubbing clean hands with pure
      ethanol in volume concentrations of 95%, 85% or 75% during 3 min was compared
      with that of the reference procedure of EN 12791 employing n-propanol 60% v/v for
      3 min, immediately and 3h after disinfection. Ethanol 85% was also tested at a 5
      min application. A Latin-square design was used with 20 randomly allotted
      volunteers. Whereas the mean immediate bacterial reductions caused by ethanol at
      concentrations of 75% (log RF 1.68) and 95% (log RF 2.70) were significantly less
      efficacious compared to that of the reference (log RF 3.27), at 85% they were not
      significantly less active with both applications, 3 and 5 min (log RFs 2.90 and
      3.12, respectively). Three hours after antisepsis, the bacterial reduction on the
      gloved hand was only significantly less efficacious than that of the reference
      when 75% ethanol was used. It is concluded that ethanol-based hand rubs have a
      good chance of meeting the EN 12791 requirements if their ethanol concentration
      is >75% v/v but <95% v/v and if they are applied for at least 3 min.

PMID- 21190756
TI  - Continuous monitoring of implemented tuberculosis control measures in middle
      income high-endemic countries.

PMID- 21190757
TI  - The inhalation anesthetic isoflurane increases levels of proinflammatory TNF
      alpha, IL-6, and IL-1beta.
AB  - Anesthetics have been reported to promote Alzheimer's disease (AD)
      neuropathogenesis by inducing beta-amyloid protein accumulation and apoptosis.
      Neuroinflammation is associated with the emergence of AD. We therefore set out to
      determine the effects of the common anesthetic isoflurane on the levels of tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1beta, the
      proinflammatory cytokines, in vitro and in vivo, employing Western blot,
      immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and reverse
      transcriptase polymerase chain reaction (RT-PCR). Here, we show that a clinically
      relevant isoflurane anesthesia increased the protein and messenger ribonucleic
      acid (mRNA) levels of TNF-alpha, IL-6, and IL-1beta in the brain tissues of mice.
      The isoflurane anesthesia increased the amounts of TNF-alpha immunostaining
      positive cells in the brain tissues of mice, the majority of which were neurons.
      Furthermore, isoflurane increased TNF-alpha levels in primary neurons, but not
      microglia cells, of mice. Finally, isoflurane induced a greater degree of TNF
      alpha increase in the AD transgenic mice than in the wild-type mice. These
      results suggest that isoflurane may increase the levels of proinflammatory
      cytokines, which may cause neuroinflammation, leading to promotion of AD
      neuropathogenesis.

PMID- 21190758
TI  - Demyelination of superficial white matter in early Alzheimer's disease: a
      magnetization transfer imaging study.
AB  - Assuming selective vulnerability of short association U-fibers in early
      Alzheimer's disease (AD), we quantified demyelination of the surface white matter
      (dSWM) with magnetization transfer ratio (MTR) in 15 patients (Clinical Dementia
      Rating Scale [CDR] 0.5-1; Functional Assessment Staging [FAST]: 3-4) compared
      with 15 controls. MTRs were computed for 39 areas in each hemisphere. We found a
      bilateral MTR decrease in the temporal, cingulate, parietal, and prefrontal
      areas. With linear discriminant analysis, we successfully classified all the
      participants with 3 variates including the cuneus, parahippocampal, and superior
      temporal regions of the left hemisphere. The pattern of dSWM changed with the age
      of AD onset. In early onset patients, we found bilateral posterior demyelination
      spreading to the temporal areas in the left hemisphere. The late onset patients
      showed a distributed bilateral pattern with the temporal and cingulate areas
      strongly affected. A correlation with Mini Mental State Examination (MMSE),
      Lexis, and memory tests revealed the dSWM impact on cognition. A specific
      landscape of dSWM in early AD shows the potential of MTR imaging as an in vivo
      biomarker superior to currently used techniques.

PMID- 21190759
TI  - Age-related effects on the neural correlates of autobiographical memory
      retrieval.
AB  - Older adults recall less episodically rich autobiographical memories (AM),
      however, the neural basis of this effect is not clear. Using functional MRI, we
      examined the effects of age during search and elaboration phases of AM retrieval.
      Our results suggest that the age-related attenuation in the episodic richness of
      AMs is associated with difficulty in the strategic retrieval processes underlying
      recovery of information during elaboration. First, age effects on AM activity
      were more pronounced during elaboration than search, with older adults showing
      less sustained recruitment of the hippocampus and ventrolateral prefrontal cortex
      (VLPFC) for less episodically rich AMs. Second, there was an age-related
      reduction in the modulation of top-down coupling of the VLPFC on the hippocampus
      for episodically rich AMs. In sum, the present study shows that changes in the
      sustained response and coupling of the hippocampus and prefrontal cortex (PFC)
      underlie age-related reductions in episodic richness of the personal past.

PMID- 21190760
TI  - Peroneal perforator flap for intraoral reconstruction.
AB  - Thin and pliable flaps with long, high calibre pedicles are ideally suited to
      lining the inside of the mouth. The radial forearm free flap has been our flap of
      choice until now, but we are unhappy with its potential for complications at the
      donor site. As an alternative, 30 patients have been treated in our unit with
      peroneal perforator flaps. Magnetic resonance (MR) angiography is necessary
      preoperatively to identify major perforating vessels. Flaps were raised using a
      lateral approach after the position of the most suitable perforator had been
      marked on the skin. The skin flaps were outlined in the proximal half of the
      lower leg with a maximum width of 5 cm to allow for direct closure of the wound.
      Five patients (of the original 35) were excluded after the results of MR
      angiography were known. All perforators identified on MR angiography could be
      exposed in the proximal half of the lower leg and most had a septocutaneous
      course. Reconstructions were in the floor of the mouth (n=16), tongue (n=11), and
      buccal mucosa (n=3). All but one flap survived with satisfactory functional
      results. The donor site morbidity was low. With the aid of MR angiography the
      peroneal perforator flap is a safe option for intraoral reconstruction. For small
      and medium sized defects we think that this flap is a good alternative to others,
      particularly if direct closure at an inconspicuous donor site is desired.

PMID- 21190761
TI  - Lumbricus terrestris L. activity increases the availability of metals and their
      accumulation in maize and barley.
AB  - The effect of the earthworm Lumbricus terrestris L. on metal availability in two
      mining soils was assessed by means of chemical extraction methods and a pot
      experiment using crop plants. Results from single and sequential extractions
      showed that L. terrestris had a slight effect on metal fractionation in the
      studied soils: only metals bound to the soil organic matter were significantly
      increased in some cases. However, we found that L. terrestris significantly
      increased root, shoot and total Pb and Zn concentrations in maize and barley for
      the soil with the highest concentrations of total and available metals.
      Specifically, shoot Pb concentration was increased by a factor of 7.5 and 3.9 for
      maize and barley, respectively, while shoot Zn concentration was increased by a
      factor of 3.7 and 1.7 for maize and barley, respectively. Our results
      demonstrated that earthworm activity increases the bioavailability of metals in
      soils.

PMID- 21190762
TI  - Biofilm responses to marine fish farm wastes.
AB  - The changes in the biofilm community due to organic matter enrichment,
      eutrophication and metal contamination derived from fish farming were studied.
      The biofilm biomass, polysaccharide content, trophic niche and element
      accumulation were quantified along an environmental gradient of fish farm wastes
      in two seasons. Biofilm structure and trophic diversity was influenced by
      seasonality as well as by the fish farm waste load. Fish farming enhanced the
      accumulation of organic carbon, nutrients, selenium and metals by the biofilm
      community. The accumulation pattern of these elements was similar regardless of
      the structure and trophic niche of the community. This suggests that the biofilm
      communities can be considered a reliable tool for assessing dissolved aquaculture
      wastes. Due to the ubiquity of biofilms and its wide range of consumers, its role
      as a sink of dissolved wastes may have important implications for the transfer of
      aquaculture wastes to higher trophic levels in coastal systems.

PMID- 21190763
TI  - Motor timing and the preparation for sequential actions.
AB  - Motor timing is essential for performing self-initiated movement sequences. Here,
      we investigated how sequence rhythm, or the timing for co-ordinating movements
      within a sequence, contributes to action preparation, compared with other
      processes occurring during sequence planning. First, we recorded the readiness
      potential (RP) in a condition of complex sequence rhythm and in condition of high
      demand on the timing for sequence initiation. We found that sequence rhythm and
      sequence initiation are independent processes, with sequence initiation
      contributing to early RP. Second, we compared the RP recorded in a condition of
      complex sequence rhythm and in a condition of complex sequence order, in which a
      complex combination of finger sub-movements had to be correctly ordered within a
      sequence. We found that sequence rhythm and sequence order share common processes
      occurring late RP. We suggest that the preparation for movement involves
      independent processes devoted to different aspects of motor timing and
      sequencing.

PMID- 21190765
TI  - Sarcoidosis with lung and systemic involvement in a 5 year old girl.

PMID- 21190764
TI  - Giant pulmonary tuberculoma: atypical form of presentation of primary
      tuberculosis in childhood.

PMID- 21190766
TI  - Prevalence of silicosis in a marble factory after exposure to quartz
      conglomerates.
AB  - In this note we present the increased prevalence of silicosis found in a marble
      factory after exposure to a new presentation of silica. A prospective,
      observational study was conducted on 11 workers who were exposed to different
      presentations of quartz surfaces since 1995. The jobs were divided into two
      groups: 4 subjects worked in the cutting workshop; the rest of the workers worked
      in assembly. Up to that date they had not used any specific respiratory
      protection apparatus. Six cases of silicosis have been diagnosed, which assumes a
      disease prevalence in this environment of 54.5%. Of the 6 affected, 5 (83.3% are
      assemblers. We highlight the high risk of developing silicosis in the handling of
      different products which make up the range of quartz surfaces.

PMID- 21190767
TI  - Guidelines for the diagnosis and treatment of thoracic traumatism.

PMID- 21190768
TI  - Accreditation of Specialist Stop Smoking Units.

PMID- 21190769
TI  - Does minimally symptomatic sleep apnea constitute a cardiovascular risk factor?

PMID- 21190770
TI  - P4 medicine: the future around the corner.
AB  - Traditional medical practice has been "reactive" (doctor takes part when disease
      appears). The theoretical (scale free networks and complex systems),
      technological (high efficiency "omic" technologies) and conceptual (biology
      systems) advances throughout the last decade, allow us to anticipate the
      transition to an "anticipatory" medicine, based on health (not on disease). This
      review establishes the conceptual bases and discusses the principal aspects of
      this new medicine, known as "P4 Medicine" standing for personalized, predictive,
      preventive and participatory.

PMID- 21190771
TI  - Comparison between two five year periods (1998/2002 and 2003/2007) on the
      production, impact and co-authorship of publications on tobacco and smoking by
      Spanish authors using the Science Citation Index.
AB  - OBJECTIVE: The aim of this study was to compare the production, impact and co
      authorship of publications by Spanish authors on smoking and tobacco between two
      time periods (1998/2002 vs 2003/2007) using Science Citation Index (SCI).
      METHODS: The literature search was performed in the SCI-Expanded on 20 November
      2008. All types of documents by Spanish authors were selected. The search was
      restricted to the title, and the key words used were "smok*" and "tobac*". The
      statistical analysis was descriptive (95% CI). RESULTS: A total of 588 documents
      were obtained, with 399 (67.85%) original papers, 54 (9.18%) letters to the
      editor, and 35 (5.95%) editorials. Productivity increased between the 98/02 to
      03/07 periods: 234 (39.8%) documents versus 354 (60.2%). We have found
      significant differences between the two periods (98/02 vs 03/07) in total mean
      annual documents (47 +/- 8 vs 71 +/- 16 [p=0.024]) and total mean annual original
      papers (34 +/- 6 vs 46 +/- 9 [p=0.041]). The mean number of citations per
      document was 14.1 +/- 2.1 for 98/02 period and 5.6 +/- 2.5 for 03/07 period
      (p=0.003). The co-authorship annual index had increased; with a mean of 6.77
      signatures/document for 98/02 period to a mean of 6.87 for 03/07 period. Authors
      and institution networks collaborations had increased between the two periods.
      CONCLUSIONS: Spanish production and co-authorship of documents on smoking and
      tobacco have increased between these two periods. The earlier period documents
      received more citations.

PMID- 21190772
TI  - Population-based study of out-of-hospital sudden cardiovascular death: incidence
      and causes of death in middle-aged adults.
AB  - INTRODUCTION AND OBJECTIVES: The data of mortality of out-of-hospital sudden
      cardiovascular death in middle-aged adults have been poorly characterized. The
      aim of this study is to analyze their epidemiological, clinical and pathological
      characteristics. METHODS: Population observational study of all cardiovascular
      deaths in people 35-49 years old in Vizcaya between 2003 and 2008. The data of
      Mortality Register and Forensic Pathology Service were analyzed. The out-of
      hospital sudden deaths subjected to forensic autopsy were identified. RESULTS:
      216 of the 465 cardiovascular deaths were sudden deaths. The main cause was
      ischemic heart disease (N=140/216). Other conditions were: cardiomyopathies
      (N=32), cerebrovascular diseases (N=19) and sudden arrhythmic death in
      structurally normal hearts (N=10). The causes varied significantly in relation to
      gender and age. Ten percent had been diagnosed in life of a cardiovascular
      disease; 66% had cardiovascular risk factors and 27% had recently consumed
      ethanol and/or abuse drugs. The incidence of sudden death was 13.2/100,000
      inhabitants/year, representing 46% of cardiovascular deaths. The incidence was
      3.77 times higher in males than in females and increased with the age.
      CONCLUSIONS: The incidence of sudden death in Vizcaya was lower than in other
      industrialized countries. In middle-aged adults out-of-hospital sudden cardiac
      death is the first manifestation of disease in half of all cardiovascular deaths.
      One challenge in prevention is the development of strategies to identify the
      highest risk people within the general population at low risk. Studies based on
      forensic autopsies improve our understanding of cardiovascular mortality.

PMID- 21190773
TI  - Secondary prevention: the ongoing challenge.

PMID- 21190774
TI  - Findings of a mixed transfemoral aortic valve implantation program using Edwards
      and CoreValve devices.
AB  - INTRODUCTION AND OBJECTIVES: Transfemoral implantation of an Edwards SAPIEN (ES)
      or Medtronic CoreValve (MCV) aortic valve prosthesis is an alternative to
      surgical replacement for patients with severe aortic stenosis and a high surgical
      risk. The study's aim was to compare results obtained with these two devices.
      METHODS: Prospective observational study of transfemoral prosthesis implantation
      performed at our center. RESULTS: Of the 76 patients (age 83 +/- 6 years, 63%
      female, logistic EuroSCORE 18 +/- 9) included, 50 were assigned the ES and 26 the
      MCV device. There was no difference between the groups in age, sex, functional
      class, valve area, associated conditions, or EuroSCORE. Implantation was
      successful in 84% of the ES group and 100% of the MCV group (P = .04). There were
      three cases of tamponade, two aortic dissections and one valve malposition in the
      ES group. The two groups had similar vascular access complication rates (26% vs.
      23%; P=NS), but pacemaker need was greater with the MCV (10% vs. 39%; P = .003).
      Mortality rates at 30 days were 12% and 20% (P = NS) in the ES and MCV groups,
      respectively, and at 1 year, 24% and 20% (P = NS), respectively. After a follow
      up of 367 +/- 266 days in the ES group and 172 +/- 159 days in the MCV group,
      three patients died. Clinical improvement was maintained in other patients and no
      echocardiographic changes were observed. CONCLUSIONS: In-hospital mortality, the
      complication rate and medium-term outcomes were similar with the two devices. The
      only difference observed was a higher implantation success rate with the MCV,
      although at the expense of a greater frequency of atrioventricular block.

PMID- 21190775
TI  - Three-dimensional echocardiography in the assessment of prosthetic valves.

PMID- 21190776
TI  - Sinus of valsalva aneurysm.

PMID- 21190777
TI  - Ultrasound study of the prevalence of plaque at the carina in lesions that affect
      the coronary bifurcation. Implications for treatment with provisional stent.
AB  - INTRODUCTION AND OBJECTIVES: The plaque distribution patterns in coronary
      bifurcation lesions are not well understood. It has been speculated that carina
      is free of plaque partly because of high wall shear stress providing an
      atheroprotective effect. To study plaque distribution with intravascular
      ultrasound (IVUS) in the coronary bifurcation and the prevalence of carina
      involvement. METHODS: IVUS study was performed on 195 coronary bifurcation
      lesions in the main vessel (MV) and on 91 in the side branch (SB). Plaque at the
      carina was considered when its thickness was > 0.3mm. Plaque burden was measured
      at different levels: proximal reference, distal, carina and at the point of
      minimal lumen area (MLA). RESULTS: The prevalence of plaque at the carina was
      32%. Its thickness was 0.8 (0.36) mm, less than that observed at the counter
      carina [1.22 (0.54) mm; P<.01]. The prevalence was higher (52%) when the MLA
      point was distal to the carina. The plaque at the carina was associated with a
      lower incidence of damage at the SB ostium after stenting the MV (32% vs 54%;
      P<.04). CONCLUSIONS: The carina is not immune to atherosclerosis, showing plaque
      at this level in one third of the bifurcations. The incidence of plaque is higher
      in those bifurcations with the MLA point distal to the carina and seems to be
      associated with a lower incidence of damage to the SB ostium.

PMID- 21190778
TI  - Comorbidity in patients admitted to a department of cardiology due to heart
      failure.

PMID- 21190779
TI  - Obesity in Castile and Leon, Spain: epidemiology and association with other
      cardiovascular risk factors.
AB  - A cross-sectional study of obesity in a random sample of 4012 individuals aged >=
      15 years in Castile and Leon, Spain, was carried out. The prevalence of obesity
      (i.e. a body mass index >= 30 kg/m2) and abdominal obesity (i.e. a waist
      circumference > 102 cm in males or > 88 cm in females) was determined and
      associations between both types of obesity and other cardiovascular risk factors
      were investigated. The overall prevalence of obesity was 21.7% (95% confidence
      interval [CI], 20.3%-23.2%): it was higher in women, at 23.2% (95% CI, 20.9%
      25.5%), than in men, at 20.4% (95% CI, 18.0%-22.7%). The prevalence of abdominal
      obesity was 36.7% (95% CI, 34.6%-38.9%): again it was higher in women, at 50.1%
      (95% CI, 47%-53.1%) than in men, at 22.8% (95% CI, 20.3%-25.2%). Associations
      were found between obesity and all classic cardiovascular risk factors, except
      smoking. The 10-year Systematic Coronary Risk Evaluation (SCORE) and Framingham
      risk scores were higher in obese individuals.

PMID- 21190780
TI  - Giant aneurysm in a coronary-pulmonary artery fistula.

PMID- 21190781
TI  - Systemic diseases and the cardiovascular system: introduction.

PMID- 21190782
TI  - An unusual complication of exercise echocardiography.

PMID- 21190783
TI  - Heyde's Syndrome.

PMID- 21190784
TI  - Transapical technique as an alternative approach to paravalvular leak closure.

PMID- 21190785
TI  - Current trends in the classification of sudden cardiac death based on autopsy
      derived data: a review of investigations into the etiology of sudden cardiac
      death.

PMID- 21190786
TI  - Monitoring stem cell proliferation and differentiation in primary midgut cell
      cultures from Heliothis virescens larvae using flow cytometry.
AB  - In the midgut of Heliothis virescens larvae, proliferation and differentiation of
      stem cell populations allow for midgut growth and regeneration. Basic epithelial
      regenerative function can be assessed in vitro by purifying these two cell type
      populations, yet efficient high throughput methods to monitor midgut stem cell
      proliferation and differentiation are not available. We describe a flow cytometry
      method to differentiate stem from mature midgut cells and use it to monitor
      proliferation, differentiation and death in primary midgut stem cell cultures
      from H. virescens larvae. Our method is based on differential light scattering
      and vital stain fluorescence properties to distinguish between stem and mature
      midgut cells. Using this method, we monitored proliferation and differentiation
      of H. virescens midgut cells cultured in the presence of fetal bovine serum (FBS)
      or AlbuMAX II. Supplementation with FBS resulted in increased stem cell
      differentiation after 5 days of culture, while AlbuMAX II-supplemented medium
      promoted stem cell proliferation. These data demonstrate utility of our flow
      cytometry method for studying stem cell-based epithelial regeneration, and
      indicate that AlbuMAX II-supplemented medium may be used to maintain pluripotency
      in primary midgut stem cell cultures.

PMID- 21190787
TI  - Isolation and identification of actinomycetes from a compost-amended soil with
      potential as biocontrol agents.
AB  - The search for new biocontrol strategies to inhibit the growth of phytopathogenic
      microorganisms has become widely widespread due to environmental concerns. Among
      actinomycetes, Streptomyces species have been extensively studied since they have
      been recognized as important sources of antibiotics. Actinomycete strains were
      isolated from a calcareous soil, 2 two-phase olive mill waste ('alperujo')
      composts, and the compost-amended soil by using selective media, and they were
      then co-cultured with 5 phytopathogenic fungi and 1 bacterium to perform an in
      vitro antagonism assay. Forty-nine actinomycete strains were isolated, 12 of them
      showing a great antagonistic activity towards the phytopathogenic microorganisms
      tested. Isolated strains were identified by 16S rDNA sequence analysis and
      phenotypic procedures. Eleven isolates concerned the genus Streptomyces and 1
      actinomycete with chitinolytic activity belonged to the genus Lechevalieria.

PMID- 21190788
TI  - Spatial wildlife-vehicle collision models: a review of current work and its
      application to transportation mitigation projects.
AB  - In addition to posing a serious risk to motorist safety, vehicle collisions with
      wildlife are a significant threat for many species. Previous spatial modeling has
      concluded that wildlife-vehicle collisions (WVCs) exhibit clustering on roads,
      which is attributed to specific landscape and road-related factors. We reviewed
      twenty-four published manuscripts that used generalized linear models to
      statistically determine the influence that numerous explanatory predictors have
      on the location of WVCs. Our motivation was to summarize empirical WVC findings
      to facilitate application of this knowledge to planning, and design of mitigation
      strategies on roads. In addition, commonalities between studies were discussed
      and recommendations for future model design were made. We summarized the type and
      measurement of each significant predictor and whether they potentially increased
      or decreased the occurrence of collisions with ungulates, carnivores, small
      medium vertebrates, birds, and amphibians and reptiles. WVCs commonly occurred
      when roads bisect favorable cover, foraging, or breeding habitat for specific
      species or groups of species. WVCs were generally highest on road sections with
      high traffic volumes, or low motorist visibility, and when roads cut through
      drainage movement corridors, or level terrain. Ungulates, birds, small-medium
      vertebrates, and carnivore collision locations were associated with road-side
      vegetation and other features such as salt pools. In several cases, results were
      spurious due to confounding and interacting predictors within the same model. For
      example, WVCs were less likely to occur when a road bisected steep slopes;
      however, steep slopes may be located along specific road-types and habitat that
      also influence the occurrence of WVCs. In conclusion, this review showed that
      much of the current literature has gleaned the obvious, broad-scale relationships
      between WVCs and predictors from available data sets, and localized studies can
      provide unique and novel results. Future research requires specific modeling for
      each target species on a road-by-road basis, and measuring the predictive power
      of model results within similar landscapes. In addition, research that builds on
      the current literature by investigating rare anomalies and interacting variables
      will assist in providing sound comprehensive guidelines for wildlife mitigation
      planning on roads.

PMID- 21190789
TI  - Concomitant rock phosphate dissolution and lead immobilization by phosphate
      solubilizing bacteria (Enterobacter sp.).
AB  - This paper examines the potential value of phosphate solubilizing bacteria
      (Enterobacter cloacae) in the dissolution of rock phosphate (RP) and subsequent
      immobilization of lead (Pb) in both bacterial growth medium and soils.
      Enterobacter sp. showed resistance to Pb and the bacterium solubilized 17.5% of
      RP in the growth medium. Enterobacter sp. did not enhance Pb immobilization in
      solution because of acidification of bacterial medium, thereby inhibiting the
      formation of P-induced Pb precipitation. However, in the case of soil,
      Enterobacter sp. increased Pb immobilization by 6.98, 25.6 and 32.0% with the RP
      level of 200, 800 and 1600 mg P/kg, respectively. The immobilization of Pb in Pb
      spiked soils was attributed to pyromorphite formation as indicated by XRD
      analysis. Inoculation of phosphate solubilizing bacteria with RP in soil can be
      used as an alternative technique to soluble P compounds which can cause
      eutrophication of surface water.

PMID- 21190790
TI  - Prediction of progression-free survival rates after bevacizumab plus interferon
      versus interferon alone in patients with metastatic renal cell carcinoma:
      comparison of a nomogram to the Motzer criteria.
AB  - BACKGROUND: The combination of bevacizumab plus interferon (BEV+IFN) for
      treatment of metastatic renal cell carcinoma (mRCC) is associated with improved
      progression-free survival (PFS) in a phase 3 study. OBJECTIVE: To develop a novel
      model for prediction of individual PFS using data from the randomized, controlled
      phase 3 trial of BEV + IFN or interferon alone. The ability of the Motzer
      criteria for prediction of PFS was also assessed. DESIGN, SETTING, AND
      PARTICIPANTS: Pretreatment parameters of 628 patients were included in the Cox
      regression model predicting PFS at 6, 12, 18, and 24 mo. BEV+IFN was administered
      to 337 patients; 291 patients received interferon alone. The developed model and
      the Motzer criteria were internally validated using Harrell's concordance index
      and calibrated. RESULTS AND LIMITATIONS: Median PFS was 10.2 versus 4.6 mo (p <
      0.001) for patients receiving BEV + IFN or interferon alone, respectively. The
      novel model relying on age, Karnofsky performance status, baseline albumin,
      alkaline phosphatase, and time from primary diagnosis to treatment resulted in
      the highest discrimination (area under the curve [AUC]: 72.8, 75.0, 72.8, and
      70.8% at 6, 12, 18, and 24 mo). The AUC of the Motzer criteria risk groups was
      63.7, 61.8, 58.6, and 51.8% for the same time points. Comparison of
      discriminatory ability between the developed model and the Motzer criteria showed
      statistically significant differences (all p <= 0.02). An external validation of
      the new model is warranted. CONCLUSIONS: The developed model identified
      prognostic factors of PFS in mRCC patients treated with BEV+IFN or interferon
      alone and quantified individual risk of PFS. Relative to the Motzer criteria, the
      novel model demonstrated better discriminatory properties. The model may serve
      clinicians in identifying patients who can benefit the most from BEV+IFN versus
      interferon alone.

PMID- 21190791
TI  - Non-risk-adapted surveillance in clinical stage I nonseminomatous germ cell
      tumors: the Princess Margaret Hospital's experience.
AB  - BACKGROUND: Since 1981 Princess Margaret Hospital has used initial active
      surveillance (AS) with delayed treatment at relapse as the preferred management
      for all patients with clinical stage I nonseminomatous germ cell tumors (NSGCT).
      OBJECTIVE: Our aim was to report our overall AS experience and compare outcomes
      over different periods using this non-risk-adapted approach. DESIGN, SETTING, AND
      PARTICIPANTS: Three hundred and seventy-one patients with stage I NSGCT were
      managed by AS from 1981 to 2005. For analysis by time period, patients were
      divided into two cohorts by diagnosis date: initial cohort, 1981-1992 (n=157),
      and recent cohort, 1993-2005 (n=214). INTERVENTION: Patients were followed at
      regular intervals, and treatment was only given for relapse. MEASUREMENTS:
      Recurrence rates, time to relapse, risk factors for recurrence, disease-specific
      survival, and overall survival were determined. RESULTS AND LIMITATIONS: With a
      median follow-up of 6.3 yr, 104 patients (28%) relapsed: 53 of 157 (33.8%) in the
      initial group and 51 of 214 (23.8%) in the recent group. Median time to relapse
      was 7 mo. Lymphovascular invasion (p<0.0001) and pure embryonal carcinoma
      (p=0.02) were independent predictors of recurrence; 125 patients (33.7%) were
      designated as high risk based on the presence of one or both factors. In the
      initial cohort, 66 of 157 patients (42.0%) were high risk and 36 of 66 patients
      (54.5%) relapsed versus 17 of 91 low-risk patients (18.7%) (p<0.0001). In the
      recent cohort, 59 of 214 patients (27.6%) were high risk and 29 of 59 had a
      recurrence (49.2%) versus 22 of 155 low-risk patients (14.2%) (p<0.0001). Three
      patients (0.8%) died from testis cancer. The estimated 5-yr disease-specific
      survival was 99.3% in the initial group and 98.9% in the recent one. CONCLUSIONS:
      Non-risk-adapted surveillance is an effective, simple strategy for the management
      of all stage I NSGCT.

PMID- 21190792
TI  - Bone turnover markers as predictors of mortality risk in prostate cancer patients
      with bone metastases following treatment with zoledronic acid.
AB  - BACKGROUND: Clinical data have limited validity for predicting the survival of
      prostate cancer (PCa) patients with bone metastases. There is a need to improve
      the predictive evidence both for clinicians and patients. OBJECTIVE: To evaluate
      the predictive ability of serum bone markers for mortality risk in PCa patients
      with bone metastases. DESIGN, SETTING, AND PARTICIPANTS: We conducted a survival
      analysis in relation to bone markers in a subgroup of 52 patients treated with
      zoledronic acid (4 mg every 4 wk for 15 mo) in a prospective, multicentre trial
      during 2002-2005, about 4 yr after the end of the trial. MEASUREMENTS: Serum
      levels of total and bone-specific alkaline phosphatase, amino-terminal
      procollagen propeptides of type I collagen (PINP), cross-linked N-terminal (NTx)
      and cross-linked C-terminal telopeptides of type I collagen (ICTP), C-terminal
      telopeptides of type I collagen, prostate-specific antigen from the last visit of
      the treatment study, and clinical data were related to the overall survival (OS)
      status of patients in the follow-up. Univariate and multivariate Cox regression
      analyses with internal bootstrapping validation and concordance index
      calculations were performed. RESULTS AND LIMITATIONS: Out of the 52 patients
      followed, 34 died within a median follow-up of 13.8 mo, and 18 patients were
      alive at a median follow-up of 43.8 mo. The patients who died within the follow
      up period had significantly higher concentrations of ICTP, NTx, and PINP than the
      surviving patients. Cox regression models with clinical data and bone markers
      showed that ICTP and PINP were most predictive for mortality risk in addition to
      the occurrence of skeletal-related complications and the continuation of
      treatment with zoledronic acid. Internal validation confirmed the reliability of
      the results, although the sample size was small. CONCLUSIONS: PINP and ICTP can
      be considered suitable predictors for the OS of PCa patients with bone
      metastases.

PMID- 21190793
TI  - Long-term follow-up of bladder cancer patients with disseminated tumour cells in
      bone marrow.
AB  - BACKGROUND: The clinical relevance of polymerase chain reaction (PCR)-based
      techniques for detection of disseminated tumour cells (DTCs) in the bone marrow
      of bladder cancer (BCa) patients is still under debate, as data on long-term
      follow-up analysis have not yet been published. OBJECTIVE: The aim of the present
      prospective study was to assess the prognostic significance of DTCs detected by
      cytokeratin-20 (CK20) reverse-transcriptase PCR in bone marrow from BCa patients
      undergoing radical cystectomy (RC). DESIGN, SETTING, AND PARTICIPANTS: Bone
      marrow samples from 51 BCa patients with high-risk non-muscle-invasive or muscle
      invasive urothelial carcinoma were drawn from the anterior iliac crest prior to
      RC. CK20-positive cells in bone marrow were detected by qualitative RT-PCR.
      MEASUREMENTS: BCa patients with CK20 status were analysed with respect to the end
      points tumour progression and cancer death. A multivariate Cox regression
      analysis was performed to determine independent prognostic factors for
      progression-free survival (PFS), tumour-specific survival (TSS), and overall
      survival (OS). RESULTS AND LIMITATIONS: CK20-positive cells were detected in 16
      of 51 (31.4%) BCa patients of all stages. BCa patients with CK20-negative status
      displayed a 7-yr PFS rate of 64% versus 35.2% for CK20-positive patients
      (p=0.007). TSS was significantly shorter in the CK20-positive group, with a 7-yr
      survival rate of 46.9% compared to CK20-negative patients with 70.2% (p=0.012).
      The 7-yr OS rate of 37.5% for CK20-positive patients was significantly <65.7% in
      the CK20-negative group (p=0.006). A subgroup analysis of lymph node-negative
      patients (pN0) discriminated by CK20 status revealed significant differences in
      PFS, TSS, and OS. In a multivariate analysis, CK20-status provides independent
      prognostic information with respect to all three survival end points.
      CONCLUSIONS: BCa patients with positive CK20 status in bone marrow represent a
      high-risk subgroup reflected by an unfavourable outcome in the long-term
      analysis.

PMID- 21190794
TI  - HPV prophylactic vaccination: The first years and what to expect from now.
AB  - New prophylactic HPV vaccines have the power to prevent many HPV infections, thus
      reducing the burden of HPV-associated diseases. Two vaccines composed of HPV L1
      proteins self assembled into virus-like particles (VLPs) have been developed: one
      containing VLPS of HPV types 6, 11, 16 and 18, while the other vaccine is
      composed of HPV 16 and 18 VLPs. Large phase II and III clinical trials to assess
      prophylactic efficacy have been conducted in which both HPV infection endpoints
      and disease endpoints were evaluated, particularly high-grade cervical
      intraepithelial neoplasia--CIN2 or CIN3--as well as vulvar and vaginal
      intraepithelial neoplasias--VIN or VaIN--and genital warts for the quadrivalent
      vaccine. Very high efficacy rates were observed in different populations that
      included young women between 16 and 26 years of age, and older (up to 55). More
      recently, the quadrivalent vaccine has been shown to be efficacious in men to
      prevent genital and anal infection and disease caused by the types included in
      the vaccine. Based on demonstrated clinical efficacy and favorable safety
      profile, HPV prophylactic vaccine are being introduced worldwide aiming the
      reduction of the morbidity and mortality of tumors caused by HPV. From 2006 when
      first approved in the USA, hundreds of countries have licensed the HPV vaccines,
      a significant proportion of which are offering the vaccine to young women in
      national immunization programs supported by the government. The ultimate goal is
      to implement worldwide cervical cancer control programs to include HPV
      vaccination and screening with cytology and HPV DNA testing, particularly in less
      developed countries where it is most needed.

PMID- 21190795
TI  - The combination of rotating disk photocatalytic reactor and TiO2 nanotube arrays
      for environmental pollutants removal.
AB  - A combined photocatalytic system on one single TiO(2)-nanotube (TNT)/Ti
      photocatalyst, which was indeed the functional combination of photon-efficient
      thin-film and conventional bulk-phase photocatalysis processes, was effectively
      developed in rotating disk photocatalytic reactor for environmental purification
      applications. The TNT/Ti rotating disk, of uniform size and well-aligned, was
      successfully prepared by direct anodic oxidation on a dominantly large surface
      area of 38 cm(2), compared to the typical 1 cm(2) in available literature. To
      estimate the potentials of combined photocatalytic system for environmental
      applications, the degradation of rhodamine B was carried out under the optimized
      conditions, a substrate removal efficiency of nearly 90% and a mineralization
      efficiency of 56% were observed for initial 20 mg/L solution after 3 h treatment.
      Compared with the combined photocatalytic system on TiO(2) nanoparticle disk, a
      significant improvement in substrate removal efficiency of about 25-40% was
      observed on TNT/Ti disk. It was confirmed that the main degradation of rhodamine
      B occurred on the upper half of TNT/Ti disk above the heavily colorized sample
      solution, which was attributed to the superior UV utilization efficiency and the
      resultant high interfacial photoactivity.

PMID- 21190796
TI  - Immobilization of Cu, Pb and Zn in mine-contaminated soils using reactive
      materials.
AB  - Immobilization processes were used to chemically stabilize soil contaminated with
      Cu, Pb and Zn from mine tailings and industrial impoundments. We examined the
      effectiveness of ordinary Portland cement (OPC), phosphoric acid and MgO at
      immobilizing Cu, Pb and Zn in soil contaminated by either mine tailings or
      industrial and mine wastes. The effectiveness was evaluated using column leaching
      experiments and geochemical modelling, in which we assessed possible mechanisms
      for metal immobilization using PHREEQC and Medusa numerical codes. Experimental
      results showed that Cu was mobilized in all the experiments, whereas Pb
      immobilization with H(3)PO(4) may have been related to the precipitation of
      chloropyromorphite. Thus, the Pb concentrations of leachates of pure mining and
      industrial contaminated soils (32-410 MUg/l and 430-1000 MUg/l, respectively)
      were reduced to 1-60 and 3-360 MUg/l, respectively, in the phosphoric acid
      experiment. The mobilization of Pb at high alkaline conditions, when Pb(OH)(4)(-)
      is the most stable species, may be the main obstacle to the use of OPC and MgO in
      the immobilization of this metal. In the mining- and industry-contaminated soil,
      Zn was retained by OPC but removed by MgO. The experiments with OPC showed the Zn
      decrease in the leachates of mining soil from 226-1960 MUg/l to 92-121 MUg/l. In
      the industrial contaminated soil, the Zn decrease in the leachates was most
      elevated, showing >2500 MUg/l in the leachates of contaminated soil and 76-173
      MUg/l in the OPC experiment. Finally, when H(3)PO(4) was added, Zn was mobilized.

PMID- 21190797
TI  - Effect of some cement components on ion contents in different brain areas of
      adult male albino mice.
AB  - The aim of this study is to investigate the chronic effect of some cement
      components on the content of ions in different brain areas in adult male albino
      mice. It is clear that chronic intraperitoneal administration of 0.0013 mg/g
      aluminum ion caused a significant increase in aluminum, calcium and sodium ions
      and significant decrease in iron ions, the chronic intraperitoneal administration
      of 0.00065 mg/g iron caused a significant increase in iron, calcium, and sodium
      ions but No significant change in potassium and aluminum ions. Chronic
      intraperitoneal administration of 0.0013 mg/g silicon caused no significant
      change in calcium, potassium, sodium, aluminum and iron. Chronic intraperitoneal
      administration of 0.0013 mg/g aluminum, 0.0013 mg/g silicon and 0.00065 mg/g
      iron, respectively, --using separating time interval 30 min between each--caused
      a higher elevation in calcium, sodium, aluminum and iron concentrations than the
      elevation in other groups and no significant change in potassium ions. This may
      be due to the elevation in glutamate which leads to increase in the intracellular
      of calcium concentration and the inhibition of membrane-bound Na(+), K(+), Ca(2+)
      ATPase activity which lead to cellular alterations and may be death. So long-term
      exposure to cement components as environmental pollutants may lead to
      neurodegenerative diseases.

PMID- 21190798
TI  - Quantitative atom probe analyses of rare-earth-doped ceria by femtosecond pulsed
      laser.
AB  - We have investigated the irradiation conditions of femtosecond laser pulses for
      quantitative atom probe analyses of rare-earth (RE) doped ceria. The influence of
      laser wavelength, power, pulse frequency, as well as specimen temperature on mass
      resolution and background noise of atom probe mass spectra were investigated.
      Furthermore, quantitative atom probe analysis of yttrium distribution in Y-doped
      ceria was carried out with the optimized evaporation conditions. The distribution
      of yttrium was found to be uniform within the grains, but they were confirmed to
      be segregated at grain boundaries.

PMID- 21190799
TI  - Quantification of the influence of friends and antisocial behaviour in adolescent
      consumption of cannabis using the ZINB model and data mining.
AB  - Cannabis is the most consumed illegal drug in Europe and its repercussions are
      more important when taken up at an early age. The aim of this study is to analyse
      and quantify the predictive value of different personal, family and environmental
      variables on the consumption of cannabis in adolescence. The sample is made up of
      9284 adolescents (47.1% boys and 52.9% girls) with an average age of 15.59 years
      (SE=1.17). The ZINB model highlights, as factors that increase the number of
      joints consumed per week, consumption by the peer group, nights out during the
      week, gender, the production of forbidden behaviour and the use of other
      substances, whereas the risk factors for the consumption of cannabis are
      consumption by friends, ease of access, production of forbidden behaviour and the
      use of other substances. Association rules highlight the relationship between
      cannabis consumption, ease of access, production of forbidden behaviour and
      tobacco consumption. Finally, decision trees enable us to predict cannabis
      consumption as well as the number of joints an adolescent will consume per week
      based on the production of forbidden behaviour, consumption of other substances
      and number of friends who consume cannabis. The results of this work have
      practical implications concerning the prevention of cannabis consumption in an
      adolescent population.

PMID- 21190800
TI  - Effect of melatonin implants on the incidence and timing of puberty in female red
      deer (Cervus elaphus).
AB  - A study was conducted to test the hypotheses that exogenous melatonin treatment
      of 11-13 month-old red deer hinds: (1) advances the timing of first ovulation,
      (2) increases the proportion of individuals attaining puberty at ~16 months of
      age, and (3) reduces the live-weight threshold for attainment of first pregnancy.
      A total of 3901 rising-2-year-old (R2) hinds within two herds (A and B) across
      two years either received single melatonin implants on two occasions in summer
      (n=1399) or were untreated controls (n=2502). Hinds were joined with stags from
      mid January to mid May, and were subjected to real-time rectal ultrasonography in
      early June to assess pregnancy status (proxy for puberty attainment) and foetal
      age for conception date assignment. Live-weights were recorded for each hind in
      January (12 months of age) as a proxy for weight at puberty. Melatonin treatment
      of hinds was associated with a significant advancement in mean conception dates
      in both herds in both years (P<0.05), with a cohort difference in mean dates
      between treated and control hinds ranging from 9 to 17 days. Analysis of the
      temporal distribution of conception dates for each cohort revealed bi-modal or
      tri-modal patterns of conception indicative of conceptions to first or subsequent
      ovulations (oestrous cycles). Across all cohorts, melatonin treatment was
      associated with higher conception rates to first ovulation (P<0.05) resulting in
      greater overall synchrony of conceptions. Regression analysis demonstrated a
      significant negative slope for conception date against live-weight (P<0.001), but
      there was no evidence that this slope varied with treatment, herd or year
      (P>0.05); for every 10kg increase in live-weight conception date was advanced by
      an average of 1.3 days. In Herd A, melatonin treatment was associated with
      significantly higher pregnancy rates in both years (90.3% vs. 78.0% in Year 1 and
      84.4% vs. 57.1% in Year 2; P<0.05). The principle effect of melatonin treatment
      was to increase the pregnancy rate of hinds of low body-mass. In Year 1, at 60kg
      live-weight a logit regression model indicated a pregnancy rate of 52% for
      untreated hinds and 83% for treated hinds. At 105kg the rate for both cohorts was
      90%. In Herd B, melatonin treatment was associated with higher conception rates
      in both years but these differences were not significant following correction for
      slight differences in mean live-weight (P>0.05). The study has demonstrated that
      factors influencing puberty attainment in R2 red deer hinds can vary between
      populations. In Herd A, in which body mass of hinds immediately prior to their
      first potential breeding season may have been the principle limiting factor,
      melatonin treatment appears to have instigated the pubertal process in hinds that
      would otherwise be of insufficient body mass.

PMID- 21190801
TI  - A method for quantifying mixed goat cashmere and sheep wool.
AB  - Cashmere is a high-priced commodity in the world market. For financial gains,
      various interested parties often adulterate cashmere with cheap sheep wool. Here,
      we describe a method that can quickly extract mitochondrial DNA from natural or
      processed animal hair. We further designed two sets of TaqMan polymerase chain
      reaction (PCR) primers and probes that can react specifically to goat and sheep
      mitochondrial 12S ribosomal RNA (rRNA) genes. Using TaqMan PCR, we can not only
      distinguish between cashmere and wool but also quantify their contents in a
      cashmere/wool mixture. The method can be applied directly to examine the quality
      of cashmere products in the world markets.

PMID- 21190802
TI  - [Renal and spleen infarction after massive consumption of cannabis and cocaine in
      a young man].
AB  - Cannabis is the most widely consumed drug in the world, particularly among young
      subjects. Cocaine is the third leading illicit drug. Cases of renal infarction
      associated with combined consumption of cannabis and cocaine have been reported
      in the literature. We describe the case of a 24-year-old man who presented renal
      and spleen infarction after massive consumption of cannabis and cocaine. Both
      vascular events arose on healthy arteries. Etiological tests were negative
      leading to the conclusion that the events resulted from a toxic cause related to
      cannabis and cocaine consumption. Different mechanisms, potentially including
      thrombosis, might explain the association of cannabis and cocaine with vascular
      events. We suggest that a systematic search for cannabis and cocaine consumption
      among young victims of vascular disease might be useful.

PMID- 21190803
TI  - [13th International congress on antiphospholipid antibodies].

PMID- 21190804
TI  - Earlier detection of tumor treatment response using magnetic resonance diffusion
      imaging with oscillating gradients.
AB  - An improved method for detecting early changes in tumors in response to
      treatment, based on a modification of diffusion-weighted magnetic resonance
      imaging, has been demonstrated in an animal model. Early detection of therapeutic
      response in tumors is important both clinically and in pre-clinical assessments
      of novel treatments. Noninvasive imaging methods that can detect and assess tumor
      response early in the course of treatment, and before frank changes in tumor
      morphology are evident, are of considerable interest as potential biomarkers of
      treatment efficacy. Diffusion-weighted magnetic resonance imaging is sensitive to
      changes in water diffusion rates in tissues that result from structural
      variations in the local cellular environment, but conventional methods mainly
      reflect changes in tissue cellularity and do not convey information specific to
      microstructural variations at sub-cellular scales. We implemented a modified
      imaging technique using oscillating gradients of the magnetic field for
      evaluating water diffusion rates over very short spatial scales that are more
      specific for detecting changes in intracellular structure that may precede
      changes in cellularity. Results from a study of orthotopic 9L gliomas in rat
      brains indicate that this method can detect changes as early as 24 h following
      treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea, when conventional approaches
      do not find significant effects. These studies suggest that diffusion imaging
      using oscillating gradients may be used to obtain an earlier indication of
      treatment efficacy than previous magnetic resonance imaging methods.

PMID- 21190805
TI  - Identification of multiple constituents in the traditional Chinese medicine
      formula Sheng-Mai San and rat plasma after oral administration by HPLC-DAD-MS/MS.
AB  - Sheng-Mai San (SMS), a traditional Chinese medicine formula, has been used for
      the treatment of cardiovascular disease in Asia over long period of time. While
      its effectiveness has been confirmed by clinical use, its active chemical
      constituents remain unclear. In this paper, an HPLC-DAD-MS/MS method is described
      for the efficient and rapid identification of the chemical constituents in SMS
      extract. MS/MS fragmentation behavior of authentic compounds was proposed for
      aiding the structural identification of the components. A total of 53 compounds
      were identified or tentatively characterized by comparing their retention times,
      UV and MS spectra with those of authentic compounds or literature data. HPLC/UV
      and MS techniques were employed to screen for the potential bioactive components
      in rat plasma after oral administration of SMS. Twenty-five compounds including
      14 prototype components and 11 metabolites were detected in dosed rat plasma
      compared with blank rat plasma. This identification and structural elucidation of
      the chemical constituents in the medicine formula and rat plasma may provide
      important experimental data for further pharmacological and clinical research.

PMID- 21190806
TI  - Enzymatic-microwave assisted extraction and high-performance liquid
      chromatography-mass spectrometry for the determination of selected veterinary
      antibiotics in fish and mussel samples.
AB  - A new method based on enzymatic-microwave assisted extraction prior to high
      performance liquid chromatography (HPLC) has been developed for the determination
      of 11 antibiotics (drugs) and the main metabolites of five of them in fish tissue
      and mussel samples. The analysed compounds were sulfadiazine (SDI), N(4)
      acetylsulfadiazine (NDI), sulfamethazine (SMZ), N(4)-acetylsulfamethazine (NMZ),
      sulfamerazine (SMR), N(4)-acetylsulfamerazine (NMR), sulfamethoxazole (SMX),
      trimetroprim (TMP), amoxicillin (AMX), amoxicilloic acid (AMA), ampicillin (AMP),
      ampicilloic acid (APA), chloramphenicol (CLF), thiamphenicol (TIF),
      oxytetracycline (OXT) and chlortetracycline (CLT). The main factors affecting the
      extraction efficiency were optimized in tissue of hake (Merluccius merluccius),
      anchovy (Engraulis encrasicolus), mussel (Mytilus sp.) and wedge sole (Solea
      solea). The microwave extraction was carried out using an extraction time of 5
      min with 5 mL of water at 50W and posterior clean up with dichloromethane. High
      performance liquid chromatography (HPLC)-mass spectrometry was used for the
      determination of the antibiotics. The separation of the analysed compounds was
      conducted by means of a Phenomenex(r) Gemini C(18) (150 mm * 4.6mm I.D., particle
      size 5 MUm) analytical column with LiChroCART(r) LiChrospher(r) C(18) (4 mm * 4
      mm, particle size 5 MUm) guard-column. Analysed drugs were determined using
      formic acid 0.1% in water and acetonitrile in gradient elution mode as mobile
      phase. Under the optimal conditions, the average recoveries of all the analysed
      drugs were in the range 70-100%. The proposed method was applied to samples
      obtained from Mediterranean sea and also evaluated by a laboratory assay
      consisting in the determination of the targeted analytes in samples of Cyprinus
      carpio that had been previously administered the antibiotics.

PMID- 21190807
TI  - Frontal affinity chromatography in characterizing immobilized receptors.
AB  - The state-of-the-art in frontal affinity chromatography (FAC) applied to receptor
      of pharmaceutical interest is here reported. This review will first discuss the
      principles of FAC for ligand characterization (K(d) determination) and for
      screening studies, and will examine the different strategies that have been
      followed for the immobilization of a broad range of receptors (cytosolic and
      membrane receptors). Several reported applications will then be presented
      demonstrating that FAC is an interesting tool enabling convenient and efficient
      screening in the identification of new potential ligands. Moreover new
      applications of FAC including dual binding site assay, receptor subtype
      characterization, and multi-receptor binding experiments will be underlined.

PMID- 21190808
TI  - [Comparison between ETCO2 values measured by the Smart CapnolineTM and the PACO2
      in intubated then extubated postoperative cardiac surgery patients].
AB  - OBJECTIVE: To compare the PaCO(2) with the ETCO(2) obtained with the Smart
      CapnolineTM in the postoperative setting of cardiac surgery during ventilation
      and after extubation TYPE OF STUDY: Prospective, observational. PATIENTS: Twenty
      patients after cardiac surgery. METHODS: In the intensive care unit, arterial
      blood gases were measured concomitantly with ETCO(2), and difference between
      PaCO(2) and ETCO(2) were calculated. Three CO(2) sensors were utilized:
      Filterline H set for intubated patients, Smart Capnoline HO(2) (nasal version)
      and Smart Capnoline O(2) (bucconasal version) after extubation. Data were
      compared with Wilconson test and the intraclass correlation coefficient was
      calculated. RESULTS: The difference PaCO(2) - ETCO(2) was significantly larger in
      extubated patients compared to intubated patients, which is also confirmed for
      the bucconasal sensor (intubated patients: 6.6 +/- 4.3 mmHg, nasal sensor: 9.3 +/
      3.5 mmHg, bucconasal sensor: 15,4 +/- 12.9 mmHg). CONCLUSION: In the
      postoperative setting of cardiac surgery, ETCO(2) measurements allow a reliable
      estimation of PaCO(2) in intubated patients in contrast to measurements in
      extubated patients. The bucconasal CO(2) sensor does not show more reliable
      measurements compared to nasal sensors in the postoperative setting of cardiac
      surgery.

PMID- 21190809
TI  - [Unexpected respiratory complication after the surgical treatment of scoliosis in
      a teenager].
AB  - We report the case of an unexpected respiratory complication after a surgical
      treatment of scoliosis during postoperative period in an adolescent patient. This
      complication results of a vascular compression of the left main bronchus between
      the aorta and the pulmonary artery, which induces severe atelectasis of left
      lower lobe. Prolonged non-invasive ventilation with high level of positive end
      expiratory pressure prevents aorto-pulmonary compression, allows a pulmonary
      recruitment associated with a favorable prognostic for the adolescent.

PMID- 21190810
TI  - Providing services in the United Kingdom to people with an intellectual
      disability who present behaviour which challenges: a review of the literature.
AB  - There is ongoing debate about the best model of service provision for people with
      an intellectual disability who present severe behavioural challenges. The present
      paper reviewed research which evaluated a range of UK service provision in terms
      of impact on challenging behaviour and other quality of life indices. A
      literature search was carried out for English language papers from 1990 to 2010
      using a range of databases. Secondary searches were carried out from references
      of relevant papers. Very few evaluations were found. The available research
      indicates that, on the whole, specialist congregate services for individuals with
      challenging behaviour appear to use more restrictive approaches which have
      limited effect on reducing challenging behaviour. The evidence for peripatetic
      teams is somewhat unclear. The two studies reviewed showed positive outcomes, but
      both had limitations that made it difficult to generalize the results. A similar
      limitation was found with the sole evaluation of a community based service. It is
      unlikely that one model of service provision will meet the needs of all
      individuals, however, more robust evaluations are required of existing service
      models to allow commissioners, service users, their families and carers to make
      fully informed choices about effective services for those who challenge.

PMID- 21190812
TI  - Leptin reduces hyperactivity in an animal model for anorexia nervosa via the
      ventral tegmental area.
AB  - Hyperactivity in anorexia nervosa (AN) is associated with low plasma leptin
      levels and negatively impacts on disease outcome. Using an animal model that
      mimics features of AN including food-restriction induced hyperlocomotion, we
      demonstrate that central leptin injections in the lateral ventricle and local
      injections of leptin into the ventral tegmental area (VTA) suppress running wheel
      activity. The results support that falling levels of leptin, that accompany
      caloric restriction, result in increased activity levels because of decreased
      leptin signaling in the VTA, part of the mesolimbic reward system.

PMID- 21190813
TI  - Self-assembled micelles based on hydrophobically modified quaternized cellulose
      for drug delivery.
AB  - Novel amphiphilic cationic cellulose (HMQC) derivatives carrying long chain alkyl
      groups as hydrophobic moieties and quaternary ammonium groups as hydrophilic
      moieties were synthesized. Structure and properties of the amphiphilic cellulose
      derivatives were characterized by elemental analysis, FT-IR, (1)H NMR, zeta
      potential measurement, dynamic light scattering (DLS), fluorescence spectroscopy
      and transmission electron microscopy (TEM). The results revealed that HMQCs can
      be self-assembled into cationic micelles in distilled water with the average
      hydrodynamic radius of 320-430 nm. The cytotoxicity study showed that the HMQC
      exhibited low cytotoxicity. Prednisone acetate, a water insoluble anti
      inflammation drug, was chosen as a model drug to investigate the utilization of
      self-assembled HMQC micelles as a delivery carrier for poorly water-soluble
      drugs. The study indicated that the prednisone acetate could be incorporated
      effectively in the self-assembled HMQC micelles and be controlled released.

PMID- 21190814
TI  - Protein arrays on high-surface-area plasma-nanotextured poly(dimethylsiloxane)
      coated glass slides.
AB  - Treatment of poly(dimethylsiloxane) (PDMS) surfaces with SF(6) plasma results in
      the creation of high-surface-area nanotextured surfaces that considerably favour
      protein adsorption with respect to untreated ones. In order to employ such
      nanotextured surfaces as substrates for microarrays to be created and analysed
      using standard instrumentation, we fabricated thin PDMS films on top of standard
      low-cost microscope glass slides. The properties of both untreated and plasma
      treated PDMS-coated slides towards spotting of protein solutions were evaluated
      in terms of spot signal intensity and homogeneity as well as of spot shape and
      size. It was found that the plasma-treated PDMS-coated glass slides provided
      highly homogeneous spots (mean intra-spot variation 7.6%) with spot signal
      intensity 6-times higher than that obtained using the untreated ones. In
      addition, comparison with commercially available polystyrene and aminosilanized
      glass microarray slides showed that the proposed slides provided 3-times higher
      spot signal intensity and 2-times lower intra-spot signal variation. In addition,
      the implementation of long-aged-after-plasma-treatment nanotextured PDMS-coated
      glass slides provided spots whose shape and size matched those of the spotting
      tip. As a consequence, denser arrays of variable spot shape can be created using
      SF(6) plasma-treated PDMS-coated slides instead of standard microarray slides
      opening new potentials for bioanalytical applications.

PMID- 21190815
TI  - Characterization of complexes formed by polypropylene imine dendrimers and anti
      HIV oligonucleotides.
AB  - Current anti-HIV therapies are capable of controlling viral infection but do not
      represent a definitive cure. They rely on the administration of antiretroviral
      nucleoside analogues, either alone or in combination with vectors. Dendrimers are
      branched, synthetic polymers with layered architectures, promising non-viral
      vectors in gene therapy. The aim of the paper was to study the interactions
      between three anti-HIV antisense oligonucleotides (ODNs): SREV, ANTI TAR, GEM91
      and different generation polypropylene imine dendrimers (PPI) by monitoring
      changes in the fluorescence polarization of fluorescein attached to the ends of
      the ODNs when increasing concentrations of dendrimers were added. Laser Doppler
      electrophoresis, dynamic light scattering (DLS) and transmission electron
      microscopy (TEM) were used to characterize, respectively, zeta potential,
      particle size and morphology of dendriplexes formed in different molar ratios.
      Antisense oligonucleotides interacted with polypropylene imine dendrimers in
      different molar ratios depending on generation. Zeta potential of dendriplexes
      varied from (-25 to -21) mV to -5 mV (for PPIG3 and PPIG4 complexes) and to zero
      (for PPIG2 complexes). The structures presented a polydisperse size from about 50
      nm to even 700-800 nm by TEM and about 250 nm by DLS. It means that besides
      single dendriplexes, aggregates were also present.

PMID- 21190816
TI  - Using isothermal titration calorimetry to real-time monitor the heat of
      metabolism: a case study using PC12 cells and Abeta(1-40).
AB  - Isothermal titration calorimetry (ITC) is one of the most powerful means for
      direct determination of thermodynamic information associated with most
      physiochemical and biological processes. The deposition and aggregation of beta
      amyloid (Abeta) on cell membranes was considered as one of the primary factors in
      having Alzheimer's disease (AD). Recently, a growing body of evidence has
      suggested that plasma membrane could accelerate the accumulation of Abeta on the
      plasma membranes. However, the mechanism of AD is still a controversial issue.
      This study provided a biothermodynamic approach to real-time monitor the heat of
      metabolism involved in the co-incubation of PC12 cells and Abeta(1-40) by ITC.
      The effects of Abeta conformation and concentration of oligomeric Abeta on
      cytotoxicity were successfully distinguished by ITC. This approach with rapid and
      direct measurement may provide not only real-time information for the effects of
      Abeta species on living cells but also a platform for the screening of drug
      candidates for AD.

PMID- 21190817
TI  - [Hemothorax and hereditary multiple exostosis in a 9-year-old boy].
AB  - We report a case of spontaneous hemothorax in a 9-year-old boy due to costal
      exostosis in the context of hereditary multiple exostosis disease. This is an
      unusual complication, whose pathophysiology remains unclear.

PMID- 21190818
TI  - Inhibition of soluble epoxide hydrolase reduces food intake and increases
      metabolic rate in obese mice.
AB  - BACKGROUND AND AIMS: This study evaluated the responses to soluble epoxide
      hydrolase (s-EH) inhibition, an essential enzyme in the metabolism of arachidonic
      acid, on food intake, body weight and metabolic parameters in mice fed a high fat
      high fructose diet (HFD) for 10 weeks. METHODS AND RESULTS: After 5 weeks of HFD,
      mice were divided into two groups: 1) s-EH inhibitor (AR9281, 200mg/kg/day by
      gavage twice daily), and 2) vehicle (0.3ml per gavage). Food intake, body weight,
      oxygen consumption (VO(2)), carbon dioxide production (VCO(2)), respiratory
      quotient (RQ), and motor activity were measured weekly for more 5 weeks. HFD
      increased body weight (37+/-1 vs. 26+/-1g), and plasma of glucose (316+/-8 vs.
      188+/-27mg/dl), insulin (62.1+/-8.1 vs. 15.5+/-5.0MUU/ml), and leptin levels
      (39.4+/-3.6 vs. 7.5+/-0.1ng/ml) while reducing VO(2), VCO(2) and motor activity.
      s-EH inhibition for 5 weeks decreased caloric intake by ~32% and increased VO(2)
      by ~17% (42.8+/-1.4 vs. 50.2+/-1.5ml/kg/min) leading to significant weight loss.
      Inhibition of s-EHi also caused significant reductions in plasma leptin levels
      and visceral fat content. Uncoupling protein 1 (UCP1) content in brown adipose
      tissue was also elevated by ~50% during s-EH inhibition compared to vehicle
      treatment. CONCLUSION: These results suggest that s-EH inhibition with AR9281
      promotes weight loss by reducing appetite and increasing metabolic rate, and that
      increased UCP1 content may contribute to the increase in energy expenditure.

PMID- 21190820
TI  - Bringing antigens to attention: a conspiracy of genes, proteins and cells.

PMID- 21190819
TI  - Genetic deletion of mPGES-1 abolishes PGE2 production in murine dendritic cells
      and alters the cytokine profile, but does not affect maturation or migration.
AB  - We undertook this study to determine the role of Microsomal PGE Synthase-1 (mPGES
      1), and mPGES-1-generated Prostaglandin (PG) E2 on Dendritic Cell (DC) phenotype
      and function. Using mPGES-1 KnockOut (KO) mice, we generated bone marrow derived
      DCs and determined their eicosanoid production profile, cell surface marker
      expression, and cytokine production. We also assessed DC migratory and functional
      capacity in vivo. Compared to wild-type, mPGES-1 deficient DCs exhibited a
      markedly attenuated increase in PGE2 production upon LPS stimulation, and
      displayed preferential shunting towards PGD2 production. mPGES-1 KO DCs did not
      display deficiencies in maturation, migration or ability to sensitize T cells.
      However, mPGES-1 deficient DCs generated reduced amounts of the Th1 cytokine IL
      12, which may in part be due to increased PGD2 rather than decreased PGE2. These
      findings provide useful information on the effects of inducible PGE2 on the
      innate immune system, and have important implications regarding potential
      consequences of pharmacologic mPGES-1 inhibition.

PMID- 21190821
TI  - What is new with Nods?
AB  - Over the last few years, much research has focused on determining the function of
      members of the cytosolic Nod-like receptor (NLR) family in terms of their
      triggers and the signaling pathways that they control. Members of this family
      include the NLRP proteins, which play a role in sensing both microbial and danger
      signals and triggering the caspase-1 dependent inflammasome, and the Nod
      subfamily characterized by proteins with a caspase-activating and recruitment
      domain (CARD) or a so-called 'X' domain. Nod1, Nod2, NLRX1 and NLRC5 are all
      members of this subfamily and in this review, we will focus on recent work that
      has shown the importance of these molecules in both pathogen sensing and
      regulation of innate and adaptive immunity.

PMID- 21190822
TI  - The sarcomeric cytoskeleton: who picks up the strain?
AB  - In striated muscle sarcomeres, the contractile actin and myosin filaments are
      organised by a subset of specialised cytoskeletal proteins, the sarcomeric
      cytoskeleton. They include alpha-actinin, myomesin, and the giant proteins titin,
      obscurin and nebulin, which combine architectural, mechanical and signalling
      functions. Mechanics and signalling in the sarcomere appear tightly
      interdependent, but the exact contributions of the various sarcomeric
      cytoskeleton proteins to strain handling or signalling are only just emerging.
      General mechanisms of cytoskeletal mechanics and signalling may be gleaned from
      the sarcomere as a specialised actomyosin system. Recent work has led to insight
      into the interactions, structure, and mechanical stability of sarcomeric protein
      complexes that fulfil both structural and signalling roles.

PMID- 21190823
TI  - Cell structure and dynamics.

PMID- 21190824
TI  - A mouse model for nonalcoholic steatohepatitis.
AB  - BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a hepatic manifestation of the
      growing metabolic syndrome epidemic that could progress to cirrhosis. Animal
      models adequately mimicking this condition in humans are scanty. AIM: The
      objective of our study was to investigate whether high-fat diets (HFD) with
      adequate methionine and choline levels can induce pathophysiological features
      typical of human NASH in C57BL/6J mice. METHODS: Forty C57BL/6J mice, divided
      into control and high-fat (HF) groups, were fed low-fat diet and HFD, ad libitum
      respectively for 20 weeks. At the end of 20 weeks, animals were sacrificed and
      assays were performed for blood biomarkers typical of human NASH. Adipose tissue
      depots were collected and liver samples were processed for histological
      examination. RESULTS: High-fat feeding led to increased triglyceride accumulation
      in the liver (8.9 MUmol/100 mg liver tissue vs. 2.6 MUmol/100 mg for control) and
      induced histopathological features of human NASH including hepatic steatosis,
      ballooning inflammation and fibrosis. Expressions of proteins and chemokines
      predominant in NASH including collagens I, III and IV and platelet derived growth
      factor (PDGF) A and B were significantly higher in animals fed the HFD. Liver
      enzymes alanine transaminase, aspartate transaminase and alkaline phosphatase
      were significantly (P<.05) elevated in the HF group compared to controls. Mice on
      HFD also developed hyperglycemia, hyperinsulinemia, hypoadiponectinemia along
      with elevated tumor necrosis factor alpha, resistin, leptin, free fatty acids,
      transforming growth factor beta and malondialdehyde levels that characterize NASH
      in humans. CONCLUSION: Long-term HF feeding with adequate methionine and choline
      can induce many of the pathophysiological features typical of human NASH in
      C57BL/6J mice.

PMID- 21190825
TI  - Black soybean extract can attenuate thrombosis through inhibition of collagen
      induced platelet activation.
AB  - Many clinical trials have demonstrated the beneficial effects of soybean (Glycine
      max) on general cardiovascular health. Among a variety of soybeans, black soybean
      is known to display diverse biological activities superior to those of yellow and
      green soybeans, such as in antioxidant, anti-inflammatory and anticancer
      activities. However, few studies have been directed on the effect of black
      soybean on cardiovascular function. In this study, we aimed to investigate the
      effect of black soybean extract (BB) on platelet activation, a key contributor to
      thrombotic diseases. In freshly isolated human platelets, BB has shown potent
      inhibitory activity on collagen-induced platelet aggregation, while yellow
      soybean extract had marginal activity only. BB also attenuated serotonin
      secretion and P-selectin expression, which are important factors for the platelet
      tissue interaction along with thromboxane A(2) formation. These in vitro results
      were further confirmed in an ex vivo platelet aggregation measurement and in vivo
      venous thrombosis model where oral administration of BB reduced collagen-induced
      platelet aggregation and FeCl(3)-induced thrombus formation significantly. A
      potential active ingredient for antiplatelet effects of BB was isolated and
      identified to be adenosine through bioassay-directed fractionation and NMR and
      ESI-MS analyses. These results indicate that black soybean can be a novel dietary
      supplement for the prevention of cardiovascular risks and the improvement of
      blood circulation.

PMID- 21190826
TI  - EGb 761 (Ginkgo biloba) protects cochlear hair cells against ototoxicity induced
      by gentamicin via reducing reactive oxygen species and nitric oxide-related
      apoptosis.
AB  - Gentamicin is an effective and powerful antibiotic. Extended use or excessive
      dosages of which can result in irreversible damage to the inner ear. The
      development of otoprotective strategies is a primary and urgent goal in research
      of gentamicin ototoxicity. Ginkgo biloba leaves and their extracts are among the
      most widely used herbal products and/or dietary supplements in the world. We
      investigated the protection of EGb 761 (a standardized preparation of EGb) on
      gentamicin ototoxicity and the involvement of reactive oxygen species (ROS) and
      nitric oxide (NO)-related mechanisms using in vitro organ cultures and an in vivo
      animal model. Gentamicin induced hair cell damage in cochlear cultures that could
      be prevented by EGb 761. EGb 761 also significantly reduced gentamicin-induced
      ROS and NO production. Furthermore, EGb 761 inhibited cellular apoptosis in
      cultured cochleae treated with gentamicin. In guinea pigs with gentamicin
      application onto the round window membrane, the mean auditory brain stem response
      threshold, ratio of cochlear hair cell damage and apoptosis were significantly
      elevated compared with those in the control group, and this could be prevented by
      oral administration of EGb 761. Individual EGb 761 components quercetin,
      bilobalide, ginkgolide A and ginkgolide B, but not kaempferol, significantly
      prevented gentamicin-induced hair cell damage. These results indicate that EGb
      761 has a protective effect against gentamicin ototoxicity through a reduction in
      the formation of ROS and NO and subsequent inhibition of hair cell apoptosis in
      the cochlea.

PMID- 21190827
TI  - An early fish oil-enriched diet reverses biochemical, liver and adipose tissue
      alterations in male offspring from maternal protein restriction in mice.
AB  - Fetal programming is linked to adulthood metabolic and chronic diseases. We
      hypothesized that early fish oil (FO) intake would revert the programming
      responses in adult offspring. Pregnant mice were fed either standard chow (SC) or
      a low-protein diet (LP) throughout pregnancy/lactation. At weaning, the following
      groups were formed: SC and SC-FO, LP and LP-FO, which were fed SC or SC+FO,
      respectively. The LP offspring are predisposed to becoming fat,
      hypercholesterolemic and hyperglycemic. In addition, during adulthood, they
      become hypertensive with hepatic steatosis and have a high level of sterol
      regulatory element binding protein (SREBP-1). However, LP offspring that were fed
      an FO-enriched diet have decreased body mass (BM) gain and lower final BM. In
      addition, with this diet, these mice have improved lipid metabolism with a
      decrease in total cholesterol (TC) and triacylglyceride (TG) levels, reduced fat
      pad masses and reduced adipocyte size. Furthermore, these LP offspring show
      reduced liver structural damage of alanine aminotransferase (ALT), liver
      steatosis with low SREBP-1 protein expression and high peroxisome proliferator
      activity receptor-alpha expression, and improvement of blood pressure (BP) and
      tumor necrosis factor (TNF)-alpha level. Early fish oil intake has beneficial
      effects on the programming responses that control body fat pad, glucose and lipid
      metabolism, and liver and adipose tissue structure in adult programmed offspring.

PMID- 21190828
TI  - Proteome alterations of cortex and hippocampus tissues in mice subjected to
      vitamin A depletion.
AB  - Vitamin A regulates the development and maintenance of the central nervous
      system. Studies of vitamin A depletion (VAD) and mutations of retinoid receptors
      in rodents have revealed a dysfunction of motor and cognitive abilities. However,
      the molecular mechanisms underlying these behavioral changes are not well
      understood. In this study, VAD mice were examined and abnormal motor behavior
      related to psychosis symptoms was found. With the use of two-dimensional gel
      electrophoresis (2-DE), two-dimensional fluorescence difference gel
      electrophoresis (2D-DIGE) and mass spectrometric (MS) technologies, 44 and 23
      altered protein spots were identified in the cortex and hippocampus,
      respectively, in VAD mice. By Western blot, the up-regulation of mitogen
      activated protein kinase 1 (MAPK1) and proteasome subunit beta type 2 (PSMB2) in
      the cortex and that of dihydropyrimidinase-related protein 2 (DPYSL2) and PSMB2
      in the hippocampus were observed in VAD mice. Bioinformatic analysis using DAVID
      revealed that altered proteins induced by VAD showed significant enrichment of
      (i) glycolysis, cytoskeleton, mitochondrion and glutamate metabolism in the
      cortex; and (ii) actin binding, dopamine receptor signaling and transmission of
      nerve impulse in the hippocampus. The up-regulations of DPYSL2, MAPK1 and PSMB2
      may indicate the activated neuronal defensive mechanism in VAD brain regions,
      which may underlie the VAD-related psychosis behavior.

PMID- 21190829
TI  - Comparison of different selenocompounds with respect to nutritional value vs.
      toxicity using liver cells in culture.
AB  - The essential micronutrient selenium (Se) exerts its biological effects mainly
      through enzymatically active selenoproteins. Their biosynthesis depends on the
      21st proteinogenic amino acid selenocysteine and thus on dietary Se supply.
      Hepatically derived selenoprotein P (SEPP) is the central selenoprotein in blood
      controlling Se transport and distribution. Kidney-derived extracellular
      glutathione peroxidase is another relevant serum selenoprotein depending on SEPP
      for biosynthesis. Therefore, secretion of SEPP by hepatocytes is crucial to
      convert nutritional sources into serum Se, supporting Se status and selenoprotein
      biosynthesis in other tissues. In order to compare the bioactivity of 10
      different selenocompounds, their dose-dependent toxicities and nutritional
      qualities to support SEPP and glutathione peroxidase biosynthesis were determined
      in a murine and two human liver cell lines. Characteristic dose- and time
      dependent effects on viability and SEPP production were observed. Incubations
      with 100 nM sodium selenite, l- or dl-selenocystine, selenodiglutathione or
      selenomethyl-selenocysteine increased SEPP concentrations in the culture medium
      up to 6.5-fold over control after 72 h. In comparison, sodium selenate, l- or dl
      selenomethionine or methylseleninic acid was less effective and increased SEPP by
      2.5-fold under these conditions. As expected, ebselen did not increase
      selenoprotein production, supporting its classification as a stable
      selenocompound. Methylseleninic acid, l-selenocystine, selenodiglutathione or
      selenite induced cell death in micromolar concentrations, whereas
      selenomethionine or ebselen was not toxic within the concentration range tested.
      Our results indicate that hepatic selenoprotein production and toxicity of
      selenocompounds do not correlate with and rather represent compound-specific
      properties. The favourable profile of selenomethylselenocysteine warrants its
      consideration as a promising option for supplementation purposes.

PMID- 21190830
TI  - Postischemic administration of liposome-encapsulated luteolin prevents against
      ischemia-reperfusion injury in a rat middle cerebral artery occlusion model.
AB  - Oxidative stress-induced neuronal cell death has been implicated in
      neurodegenerative diseases; one such disease is ischemic stroke. Using reactive
      oxygen species (ROS)-insulted primary neurons, we screened neuroprotectants with
      clinical potential and then, using ischemia/reperfusion (I/R) model, investigated
      the anti-ischemic potential of candidate neuroprotectants. Here, we showed that
      luteolin, isolated from the ripe fruit of Perilla frutescens (L.) Britt,
      exhibited a neuroprotective action upon the in vitro platform, thus serving as
      candidate for in vivo pharmacological evaluation. Liposome-encapsulated luteolin
      produced dramatic preventing effects on I/R-induced behavioral and histological
      injuries after a 13-day post-ischemic treatment. Furthermore, this phytochemical
      not only lowered the increased level of mitochondrial ROS but also substantially
      up-regulated the decreased activity of catalase and glutathione in I/R rat
      brains. Collectively, luteolin as a neuroprotectant acts by anti-ischemic
      activity likely through a rebalancing of pro-oxidant/antioxidant status. Its
      multitarget mechanisms implicate potential effectiveness for clinically treating
      ischemia stroke.

PMID- 21190831
TI  - Wogonin promotes cholesterol efflux by increasing protein phosphatase 2B
      dependent dephosphorylation at ATP-binding cassette transporter-A1 in
      macrophages.
AB  - Wogonin, one component in Scutellaria baicalensis Georgi extracts, has several
      beneficial properties for cancers and inflammatory diseases. However, the
      efficacy of wogonin in cholesterol metabolism of macrophages remains unknown. In
      macrophages, cholesterol uptake is controlled by scavenger receptors (SR-A and
      CD36) and cholesterol efflux by SR-BI, ATP-binding cassette transporter-A1
      (ABCA1) and ABCG1. In the present study, we investigated the effect and
      underlying molecular mechanism of wogonin on the formation of macrophage foam
      cells by murine J774.A1 macrophages. Wogonin attenuated oxidized low-density
      lipoprotein (oxLDL)-induced cholesterol accumulation in macrophages. The binding
      of oxLDL to macrophages and protein expression of SR-A and CD36 were not affected
      by wogonin. Wogonin enhanced cholesterol efflux and increased the protein level
      of ABCA1 without affecting the protein expression of SR-BI or ABCG1. Inhibition
      of ABCA1 by pharmacological inhibitor 4,4'-diisothiocyanatostilbene-2,2'
      disulfonic acid disodium salt or neutralizing antibody abolished this suppressive
      effect of wogonin on lipid accumulation. Moreover, the up-regulation of ABCA1
      protein by wogonin resulted from a decrease in degradation rate of ABCA1 protein,
      with no effect on ABCA1 mRNA expression. This reduction in ABCA1 degradation was
      due to increased protein phosphatase 2B (PP2B)-mediated ABCA1 dephosphorylation,
      as evidenced by increased interaction between ABCA1 and PP2B; pharmacological
      inhibition of PP2B would prevent wogonin-induced ABCA1 protein expression,
      dephosphorylation and attenuation of lipid accumulation. Collectively, wogonin
      increases the protein stability of ABCA1 via PP2B-mediated dephosphorylation,
      thus leading to reduced cholesterol accumulation in macrophage foam cells.

PMID- 21190832
TI  - Maternal malnutrition programs pancreatic islet mitochondrial dysfunction in the
      adult offspring.
AB  - Accumulating evidence has shown that maternal malnutrition increases the risk of
      metabolic disease in the progeny. We previously reported that prenatal exposure
      to a low-protein diet (LP) leads to mitochondrial dysfunction in pancreatic
      islets from adult rodent offspring that could relate physiological and cellular
      alterations due to early diet. We aim to determine whether mitochondrial
      dysfunction could be a common consequence of prenatal nutritional unbalances.
      Pregnant Wistar rats received either a global food restriction (GFR), consisting
      in the reduction by 50% of the normal daily food intake, or a high-fat diet (HF)
      throughout gestation. GFR or HF diet during pregnancy leads to a lack of increase
      in insulin release and ATP content in response to glucose stimulation in islets
      from 3-month-old male and female offspring. These similar consequences originated
      from impairment in either glucose sensing or glucose metabolism, depending on the
      type of early malnutrition and on the sex of the progeny. Indeed, the glucose
      transport across beta-cell membrane seemed compromised in female HF offspring,
      since GLUT-2 gene was markedly underexpressed. Additionally, for each progeny,
      consequences downstream the entry of glucose were also apparent. Expression of
      genes involved in glycolysis, TCA cycle and oxidative phosphorylations was
      altered in GFR and HF rats in a sex- and diet-dependent manner. Moreover,
      prenatal malnutrition affected the regulators of mitochondrial biogenesis,
      namely, PPAR coactivator 1 alpha (PGC-1alpha), since its expression was higher in
      islets from GFR rats. In conclusion, programming of mitochondrial dysfunction is
      a consequence of maternal malnutrition, which may predispose to glucose
      intolerance in the adult offspring.

PMID- 21190833
TI  - S-Allylcysteine, a garlic compound, protects against oxidative stress in 1-methyl
      4-phenylpyridinium-induced parkinsonism in mice.
AB  - S-Allylcysteine (SAC), the most abundant organosulfur compound in aged garlic
      extract, has multifunctional activity via different mechanisms and
      neuroprotective effects that are exerted probably via its antioxidant or free
      radical scavenger action. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      treated mouse has been the most widely used model for assessing neuroprotective
      agents for Parkinson's disease. 1-Methyl-4-phenylpyridinium (MPP(+)) is the
      stable metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and it causes
      nigrostriatal dopaminergic neurotoxicity. Previous studies suggest that oxidative
      stress, via free radical production, is involved in MPP(+)-induced neurotoxicity.
      Here, we report on the neuroprotective effect of SAC against oxidative stress
      induced by MPP(+) in the striatum of C57BL/6J mice. Mice were pretreated with SAC
      (125 mg/kg ip) daily for 17 days, followed by administration of MPP(+) (0.72
      mg/kg icv), and were sacrificed 24 h later to evaluate lipid peroxidation,
      different antioxidant enzyme activities, spontaneous locomotor activity and
      dopamine (DA) content. MPP(+) administration resulted in a significant decrease
      in DA levels in the striatum. Mice receiving SAC (125 mg/kg ip) had significantly
      attenuated MPP(+)-induced loss of striatal DA levels (32%). The neuroprotective
      effect of SAC against MPP(+) neurotoxicity was associated with blocked (100% of
      protection) of lipid peroxidation and reduction of superoxide radical production 
      indicated by an up-regulation of Cu-Zn-superoxide dismutase activity - both of
      which are indices of oxidative stress. Behavioral analyses showed that SAC
      improved MPP(+)-induced impairment of locomotion (35%). These findings suggest
      that in mice, SAC attenuates MPP(+)-induced neurotoxicity in the striatum and
      that an antioxidant effect against oxidative stress may be partly responsible for
      its observed neuroprotective effects.

PMID- 21190834
TI  - Mycophenolate, clinical pharmacokinetics, formulations, and methods for assessing
      drug exposure.
AB  - This article summarizes part of a consensus meeting about mycophenolate (MPA)
      therapeutic drug monitoring held in Rome under the auspices of The
      Transplantation Society in November 2008 (Clin J Am Soc Nephrol. 2010;5:341-358).
      This part of the meeting focused on the clinical pharmacokinetics of MPA and
      included discussion on how to measure MPA (active drug) exposure and the
      differences between the currently available formulations. SUMMARY POINTS: Because
      of variability in the dose-concentration relationship, MPA exposure should be
      measured and doses should be adjusted accordingly to achieve optimal clinical
      outcomes. Suggested therapeutic exposures derived for MPA from mycophenolate
      mofetil (MMF) may differ to those that could be useful for MPA from enteric
      coated mycophenolate sodium (EC-MPS), particularly if limited sampling strategies
      or single concentration, especially trough concentrations, is used, as the
      concentration-time profiles of MPA from the 2 formulations are quite different.
      The 2 MPA formulations cannot be considered as bioequivalent. The area under the
      concentration-time curve (AUC 0-12) is considered the criterion standard for
      monitoring of MPA, which is a reflection of exposure to the drug over the entire
      dosing period. If a limited sampling protocol coupled with multilinear regression
      or Bayesian estimation is used to estimate this parameter, it should be used only
      for the population in which the model has been developed and should preferably
      include at least one time point after 4 hours (preferably around 8 or 9 hours
      after MMF dosing). If a single time point is to be used as a surrogate for an AUC
      0-12, trough concentration of MPA may be the most practical but, from a
      pharmacokinetic standpoint, is not the most informative time point to choose.
      Because limited sampling strategies to estimate MPA exposure from EC-MPS have not
      yet been well developed and fully evaluated, nor have accurate Bayesian
      estimators been reported, AUC 0-12 measurement is still necessary to obtain
      reliable estimates of MPA exposure in patients treated with EC-MPS. The
      measurement of MPA trough concentrations should not be used at all for MPA
      exposure assessment following administration of EC-MPS. Because limited sampling
      strategies to estimate MPA exposure from EC-MPS have not yet been well developed
      and fully evaluated, nor have accurate Bayesian estimators been reported, AUC 0
      12 measurement is still necessary to obtain reliable estimates of MPA exposure in
      patients treated with EC-MPS. The measurement of MPA trough concentrations should
      not be used at all for MPA exposure assessment following administration of EC
      MPS. Lower (or higher) than expected total MPA exposure in patients with severe
      renal impairment may still indicate sufficient free MPA exposure. Mycophenolate
      free exposure measurement/estimation is likely to be beneficial in patients with
      severe renal impairment (creatinine clearance b25 mL/min) to guide dosage
      estimation, especially because renal function changes over time after transplant,
      while recognizing that robust prospective studies to show the clinical advantage
      of measuring free MPA exposure are still required. Lower total measured MPA
      exposure in patients with hypoalbuminemia may still indicate sufficient free MPA
      exposure. Mycophenolate free concentration measurement and estimation of exposure
      are likely to be beneficial in patients with a serum albumin less than or equal
      to 31 g/L to guide interpretation of MPA exposure. A 1.5-g twice-daily starting
      dose of MMF rather than a 1-g twice-daily starting dose of MMF is more likely to
      achieve the minimum target MPA exposure in adult transplant recipients receiving
      concomitant cyclosporine therapy. Because the cyclosporine dose is progressively
      tapered following transplantation, MPA exposure should be measured repeatedly and
      MMF should be doses adjusted accordingly to achieve optimal clinical outcome.
      Mycophenolate exposure should be measured in the first week after transplant,
      then each week for the first month, each month until month 3, and subsequently
      every 3 months up to 1 year with appropriate dosage adjustment, as AUC is likely
      to increase over time. After 1 year, if dosage requirement has stabilized, MPA
      exposure can be assessed each time the immunosuppressive regimen is changed or a
      potentially interacting drug is introduced or withdrawn. Assessment of UGT1A9
      single nucleotide polymorphisms (-275TNA, -2152CNT, -440CNT, -331TNC) should be
      considered before transplantation to assist in dosing decisions to achieve
      optimal MPA exposure immediately after transplant. Consideration of the points
      summarized above should lead to more effective dosage adjustment based on sound
      applied pharmacokinetic and pharmacodynamic principles.

PMID- 21190835
TI  - Microfluidic chip-based nanoelectrode array as miniaturized biochemical sensing
      platform for prostate-specific antigen detection.
AB  - A microfluidic biosensor chip with an embedded three-electrode configuration is
      developed for the study of the voltammetric response of a nanoelectrode array
      with controlled inter-electrode distance in a nanoliter-scale sample volume. The
      on-chip three-electrode cell consists of a 5 * 5 array of Au working
      nanoelectrodes with radii between 60 and 120 nm, a Cl(2)-plasma-treated Ag/AgCl
      reference electrode, and a Au counter electrode. The nanoelectrode array is
      fabricated by creating high-aspect-ratio pores through an alumina insulating
      layer using an I(2) gas-assisted focused-ion-beam (FIB) milling, ion beam
      sculpting, and electrodeposition of Au. The glass substrate with the electrode
      pattern is assembled with a polydimethylsiloxane (PDMS) microchannel slab giving
      a volume of 180 nL for each channel. Cyclic voltammetry calibration with a
      standard redox species exhibits a significant increase of current density by two
      orders of magnitude compared to that obtained from a microelectrode. On-chip
      functionalization of the nanoelectrodes with a prostate-specific antigen (PSA)
      biosensor complex and detection of PSA based on a competitive immunoassay method
      are performed. The detection limit is approximately 10 pg/mL (~270 fM), which
      corresponds to roughly 30,000 copies of PSA in the microchannel test volume.

PMID- 21190836
TI  - Carbon nanotube powders as electrode modifier to enhance the activity of anodic
      biofilm in microbial fuel cells.
AB  - Carbon nanotube (CNT) is a promising electrode material and has been used as an
      anode modifier in microbial fuel cells (MFCs). In this study, a new method of
      simultaneously adding CNT powders and Geobacter sulfurreducens into the anode
      chamber of a MFC was used, aiming to form a composite biofilm on the anode. The
      performance of MFCs such as startup time and steady-state power generation was
      investigated under conditions of different CNT powders dosages. Results showed
      that both the startup time and the anodic resistance were reduced. The optimal
      dosage of CNT powders pre-treated by acid was 4 mg/mL for the anode chamber with
      an effective volume of 25 mL. The anodic resistance and output voltage of the MFC
      with CNT powders addition were maintained around 180 Omega and 650 mV during 40
      days operation, while those of the MFC without CNT powders addition increased
      from 250 Omega to 540 Omega and decreased from 630 mV to 540 mV, respectively,
      demonstrating that adding CNT powders helped stabilize the anodic resistance,
      thus the internal resistance and power generation during long-term operation.
      Based on cyclic voltammogram, the electrochemical activity of anodic biofilm was
      enhanced by adding CNT powders, though no significant increase of the biomass in
      anodic biofilm was detected by phospholipids analysis. There was no remarkable
      change of ohmic resistance with an addition of CNT powders revealed by current
      interrupt method, which indicated that the rate of mass transfer might be
      promoted by the presence of CNT powders.

PMID- 21190837
TI  - Chitosan-iron oxide nano-composite platform for mismatch-discriminating DNA
      hybridization for Neisseria gonorrhoeae detection causing sexually transmitted
      disease.
AB  - Electrochemically fabricated nano-composite film of chitosan (CH)-iron oxide
      (Fe(3)O(4)) has been used to detect gonorrhoea, a sexually transmitted disease
      (STD) via immobilization of biotinylated probe DNA (BDNA) using avidin-biotin
      coupling for rapid and specific (mismatch-discriminating) DNA hybridization. The
      presence of Fe(3)O(4) nanoparticles (~18nm) increases the electro-active surface
      area of the nano-biocomposite that provides desirable environment for loading of
      DNA with better conformation leading to increased electron transfer kinetics
      between the medium and electrode. The differential pulse voltammetric (DPV)
      studies have been conducted using BDNA/avidin/CH-Fe(3)O(4)/ITO electrode owing to
      the reduction of the methylene blue (MB) indicator and investigate electron
      transfer between MB moieties and electrode for one and two-bases mismatch. This
      STD biosensor is found to have a detection limit (1 * 10(-15)M) and a wide
      dynamic range (from 1 * 10(-16)M to 1 * 10(-6)M) using the complementary target
      DNA. In addition, the sensing system can be utilized to accurately discriminate
      complementary sequence from mismatch sequences.

PMID- 21190838
TI  - From good old biochemical analyses to high-throughput omics measurements and
      back.

PMID- 21190839
TI  - Conventional craniospinal irradiation with patient supine and source-skin
      distance (SSD) 100 cm for spinal field.
AB  - We describe a method of craniospinal irradiation (CSI) in the supine position and
      at a source-skin distance (SSD) of 100 cm for the spinal fields. The procedure is
      carried out with a 100-cm isocenter linear accelerator and conventional
      simulator, and the treatment is delivered with 2 opposed lateral cranial fields
      at source-axis distance (SAD) of 100 cm and 1 or 2 direct posterior spinal fields
      at SSD, 100 cm. The half beam-blocked cranial fields with a collimator rotation
      is used to match the superior border of the spinal field at the level of C2
      vertebral body. The length of the spinal field is fixed, and is the same if 2
      spinal fields are used. The position of the isocenter of the spine field is
      defined by longitudinally moving the couch a distance from the isocenter of the
      cranial fields and adjusting the SSD = 100 cm to the surface of the couch with
      the gantry rotated to the angle of 180 degrees  (posteroanterior position), and
      the distance can be calculated easily according to a few parameters. It only
      needs a simple calculation without couch rotation, extended SSD, or markers. The
      inferior and superior borders of the spinal field do not require visualization
      under fluoroscopy when it is beyond the visual field of the simulator. The entire
      simulation takes no more than 20 minutes. Supine craniospinal treatment using
      this technique may substitute the traditional prone position as a potentially
      beneficial alternative to CSI.

PMID- 21190840
TI  - High-rate partial nitrification treatment of reject water as a pretreatment for
      anaerobic ammonium oxidation (anammox).
AB  - In this study, a lab-scale swim-bed partial nitrification reactor was developed
      to treat ammonium-rich reject water to achieve an appropriate NO(2)(-)-N/NH(4)(+)
      N mixture that could serve as a pretreatment for anaerobic ammonium oxidation
      (anammox). Strictly controlling the DO concentration was adopted as the main
      operational strategy. In addition, the influent concentrations of inorganic
      carbon/ammonium (IC/NH(4)(+)) and alkalinity/ammonium (Alk/NH(4)(+)) that were
      approximately 0.8 and 4.8, respectively, were regarded as the suitable ratios for
      the steady and high-rate operation of the reactor in this study. When reject
      water that was not diluted was introduced to this system, the maximum nitrogen
      loading rate was 5.9 kg-N/m(3)/day, the ammonium conversion rate was 3.1 kg
      N/m(3)/day, and the effluent NO(2)-N/(NO(2)-N+NO(3)-N) percentage ratio was over
      99.9%. Furthermore, DNA analysis confirmed the existence of AOB, which was
      responsible for the stable performance that was achieved in the PN reactor.

PMID- 21190841
TI  - Solid-state fermentation of agro-industrial wastes to produce bioorganic
      fertilizer for the biocontrol of Fusarium wilt of cucumber in continuously
      cropped soil.
AB  - Agro-industrial wastes of cattle dung, vinegar-production residue and rice straw
      were solid-state fermented by inoculation with Trichoderma harzianum SQR-T037
      (SQR-T037) for production of bioorganic fertilizers containing SQR-T037 and 6
      pentyl-alpha-pyrone (6PAP) to control Fusarium wilt of cucumber in a continuously
      cropped soil. Fermentation days, temperature, inoculum and vinegar-production
      residue demonstrated significant effects on the SQR-T037 biomass and the yield of
      6PAP, based on fractional factorial design. Three optimum conditions for
      producing the maximum SQR-T037 biomass and 6PAP yield were predicted by central
      composite design and validated. Bioorganic fertilizer containing 8.46 log(10) ITS
      copies g(-1) dry weight of SQR-T037 and 1291.73 mg kg(-1) dry weight of 6PAP, and
      having the highest (p<0.05) biocontrol efficacy, was achieved at 36.7
      fermentation days, 25.9 degrees C temperature, 7.6% inoculum content, 41.0%
      vinegar-production residue, 20.0% rice straw and 39.0% cattle dung. This is a way
      to offer a high value-added use for agro-industrial wastes.

PMID- 21190842
TI  - Pyrolysis of grape bagasse: effect of pyrolysis conditions on the product yields
      and characterization of the liquid product.
AB  - In this study, pyrolysis of grape bagasse was investigated with the aim to study
      the product distribution and their chemical compositions and to identify optimum
      process conditions for maximizing the bio-oil yield. Particular investigated
      process variables were temperature (350-600 degrees C), heating rate (10-50
      degrees C/min) and nitrogen gas flow rate (50-200 cm(3)/min). The maximum oil
      yield of 27.60% was obtained at the final pyrolysis temperature of 550 degrees C,
      sweeping gas flow rate of 100 cm(3)/min and heating rate of 50 degrees C/min in a
      fixed-bed reactor. The elemental analysis and heating value of the bio-oils were
      determined, and then the chemical composition of the bio-oil was investigated
      using chromatographic and spectroscopic techniques such as column chromatography,
      (1)H NMR and FTIR. The fuel properties of the bio-oil such as flash point,
      viscosity and density were also determined. The bio-oils obtained from grape
      bagasse were presented as an environmentally friendly feedstock candidate for bio
      fuels.

PMID- 21190843
TI  - Feasibility study of a cyclic anoxic/aerobic two-stage MBR for treating ABS resin
      manufacturing wastewater.
AB  - This study investigated the feasibility and the treatment efficiency of a cyclic
      anoxic/aerobic two-stage MBR for treating polymeric industrial wastewater. The
      anoxic/aerobic hybrid MBR was operated without sludge withdrawal except sampling
      during the study. The results showed that the highest COD organic loading rate of
      8.7 kg COD/m(3) day from bioreactor was obtained at phase 3. The system achieved
      97% BOD(5) and 89% COD removal. It also revealed that 93% of COD removal was
      contributed by bioreactor at phase 3 and the similar results happened to phases 1
      and 2. The highest TN and TKN removals for each phase were 60, 74, 80% and 61,
      74, 81%, respectively and limited by nitritation step. SEM images of nascent and
      fouled membranes were offered to evaluate the cleaning method. The system was
      operated for 174 days, resulting in high degradation rate, flexibility towards
      influent fluctuations and limited sludge production.

PMID- 21190844
TI  - Biodiesel production from pomace oil by using lipase immobilized onto olive
      pomace.
AB  - In the present work, microbial lipase from Thermomyces lanuginosus was
      immobilized by covalent binding onto olive pomace. Immobilized support material
      used to produce biodiesel with pomace oil and methanol. The properties of the
      support and immobilized derivative were evaluated by scanning electron microscopy
      (SEM). The maximum immobilization of T. lanuginosus was obtained as 18.67 mg/g
      support and the highest specific activity was 10.31 U/mg protein. The properties
      of immobilized lipase were studied. The effects of protein concentration, pH and
      buffer concentration on the immobilization and lipase activity were investigated.
      Biodiesel production using the immobilized lipase was realized by a three-step
      addition of methanol to avoid strong substrate inhibition. Under the optimized
      conditions, the maximum biodiesel yield was 93% at 25 degrees C in 24h reaction.
      The immobilized enzyme retained its activity during the 10 repeated batch
      reactions.

PMID- 21190845
TI  - The effect of Ni(II) on properties of bulking activated sludge and microbial
      analysis of sludge using 16S rDNA gene.
AB  - This study investigated the effect of nickel on properties and microbial
      community of bulking activated sludge when 60-240 mg/L Ni(II) was dosed
      continuously in a sequencing batch reactor (SBR) over 350 days. Results showed
      that 120 mg/L nickel did not significantly inhibited removal of organic pollutant
      by activated sludge. However, the system was completely upset when 240 mg/L
      Ni(II) was dosed. Improvement of settling and dewatering ability was also
      observed with the addition of Ni(II). In addition, investigations by polymerase
      chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) of 16S rDNA of
      bacteria strain demonstrated that Ni(II) significantly affected microbial
      community of bulking activated sludge, judging from the elimination of original
      species and emergence of possible new nickel-resistant bacteria. The effect of
      nickel on shift of microbial community was an important cause resulted in the
      improvement of sludge properties in this bulking activated sludge system.

PMID- 21190846
TI  - Optimization of thermal-dilute sulfuric acid pretreatment for enhancement of
      methane production from cassava residues.
AB  - In this study, the pretreatment of cassava residues by thermal-dilute sulfuric
      acid (TDSA) hydrolysis was investigated by means of a statistically designed set
      of experiments. A three-factor central composite design (CCD) was employed to
      identify the optimum pretreatment condition of cassava residues for methane
      production. The individual and interactive effects of temperature, H(2)SO(4)
      concentration and reaction time on increase of methane yield (IMY) were evaluated
      by applying response surface methodology (RSM). After optimization, the resulting
      optimum pretreatment condition was 157.84 degrees C, utilizing 2.99% (w/w TS)
      H(2)SO(4) for 20.15 min, where the maximum methane yield (248 mL/g VS) was 56.96%
      higher than the control (158 mL/g VS), which was very close to the predict value
      56.53%. These results indicate the model obtained through RSM analysis is suit to
      predict the optimum pretreatment condition and there is great potential of using
      TDSA pretreatment of cassava residues to enhance methane yield.

PMID- 21190848
TI  - 1-(Arylsulfonyl)-2,3-dihydro-1H-quinolin-4-one derivatives as 5-HT(6) serotonin
      receptor ligands.
AB  - Piperazinyl derivatives of 1-(arylsulfonyl)-2,3-dihydro-1H-quinolin-4-ones have
      been identified with high binding affinities for 5-HT(6) receptor. In particular,
      2-methyl-5-(N-methyl-piperazin-1-yl)-1-(naphthalene-2-sulfonyl)-2,3-dihydro-1H
      quinolin-4-one (8g) exhibits high binding affinity toward 5-HT(6) (IC(50)=8nM)
      receptor with good selectivity over other serotonin and dopamine receptors.

PMID- 21190847
TI  - Wastewater treatment by alkali bacteria and dynamics of microbial communities in
      two bioreactors.
AB  - In this study, an alkali bacterial consortium was obtained by enrichment
      cultivation and was used to treat printing and dyeing wastewater (PDW, pH 11-12).
      The treatment effects and dynamic changes were evaluated in a biocontact
      oxidation reactor (BOR) and a sequencing batch reactor (SBR). During 3 months of
      continuous operation, the two bioreactors had similar treatment efficiencies
      (polyvinyl alcohol, PVA, 74.5-81.3%; COD, 73.5-77.4%; 2.15 pH decreases).
      Molecular biological analysis indicated that the microbial communities underwent
      dramatic changes during the operation, in which the SBR was superior to the BOR
      in retaining the alkali bacteria at the start-up stage, however, the BOR seemed
      to be more advantageous when the frequently changing influents were considered.
      The bacterial communities in BOR and SBR were diverse and included Bacteroidetes,
      Firmicutes, Proteobacteria, Actinobacteria and an unidentified cluster. Among
      these only Paracoccus sp. was successfully isolated and confirmed to have the
      ability to degrade PVA.

PMID- 21190849
TI  - 2,4-Diaminopyrimidine inhibitors of c-Met kinase bearing benzoxazepine anilines.
AB  - Elaboration of the SAR around a series of 2,4-diaminopyrimidines led to a number
      of c-Met inhibitors in which kinase selectivity was modulated by substituents
      appended on the C4-aminobenzamide ring and the nature of the C2-aminoaryl ring.
      Further lead optimization of the C2-aminoaryl group led to benzoxazepine analogs
      whose pharmaceutical properties were modulated by the nature of the substituent
      on the benzoxazepine nitrogen. Tumor stasis (with partial regressions) were
      observed when an orally bioavailable analog was evaluated in a GTL-16 tumor
      xenograft mouse model. Subsequent PK/PD studies suggested that a metabolite
      contributed to the overall in vivo response.

PMID- 21190850
TI  - Structure based evolution of a novel series of positive modulators of the AMPA
      receptor.
AB  - Starting from compound 1, we utilized biostructural data to successfully evolve
      an existing series into a new chemotype with a promising overall profile,
      exemplified by 19.

PMID- 21190851
TI  - Quinazolinones as gamma-secretase modulators.
AB  - Synthesis, SAR and evaluation of styrenyl quinazolinones as novel gamma secretase
      modulators are presented in this communication. Starting from literature and in
      house leads we evaluated a range of quinazolinones which showed good modulation
      of gamma-secretase activity.

PMID- 21190853
TI  - Synthesis of modified siRNA bearing C-5 polyamine-substituted pyrimidine
      nucleoside in their 3'-overhang regions and its RNAi activity.
AB  - Short interfering RNA (siRNA) induces specific gene silencing by the RNA
      interference (RNAi) pathway. Nucleosides in the 3'-overhang regions of siRNAs
      were replaced with 5-bis(aminoethyl)aminoethylcarbamoylmethyl-2'-deoxyuridine or
      thymidine. siRNA bearing modified nucleoside was more active in silencing the
      gene expression of hepatocyte nuclear factor 4alpha (HNF4alpha) compared with
      siRNA bearing thymidine.

PMID- 21190852
TI  - Synthesis of 'clickable' acylhomoserine lactone quorum sensing probes:
      unanticipated effects on mammalian cell activation.
AB  - Alkynyl- and azido-tagged 3-oxo-C(12)-acylhomoserine lactone probes have been
      synthesized to examine their potential utility as probes for discovering the
      mammalian protein target of the Pseudomonas aeruginosa autoinducer, 3-oxo-C(12)
      acylhomoserine lactone. Although such substitutions are commonly believed to be
      quite conservative, from these studies, we have uncovered a drastic difference in
      activity between the alkynyl- and azido-modified compounds, and provide an
      example where such structural modification has proved to be much less than
      conservative.

PMID- 21190855
TI  - Antioxidant activity of N-acyl chitosan oligosaccharide with same substituting
      degree.
AB  - N-Maleoyl chitosan oligosaccharide (NMCOS) and N-succinyl chitosan
      oligosaccharide (NSCOS) were prepared by acylation with maleic anhydride and
      succinic anhydride, respectively. Their structural changes were confirmed by
      Fourier-transform infrared (FT-IR) spectroscopy and their substituting degrees
      were determined both as 0.49 by conductometric titration. Their antioxidant
      activities were evaluated by scavenging superoxide anion O(2.)(-), hydroxyl
      radical ()OH and determination of reducing power. The 50% inhibition
      concentrations (IC(50)) of NMCOS and NSCOS scavenging effect on O(2)(.-) were
      2.25 and 3.27mg/mL, respectively. The IC(50) of NMCOS scavenging effect on (.)OH
      was 0.24mg/mL, however, at the same concentration determined, the value of NSCOS
      on (.)OH was 30.5%. The reducing powers of NMCOS and NSCOS at the concentration
      of 2.40mg/mL were determined as 0.46 and 0.41, respectively. The above results
      showed that NMCOS has better antioxidant activities, which may be related to the
      fact that maleoyl has stronger electron-withdrawing effect than succinyl.

PMID- 21190854
TI  - New Hedgehog/GLI signaling inhibitors from Excoecaria agallocha.
AB  - The inhibition of the Hedgehog (Hh) signaling pathway has emerged as an anti
      cancer strategy. Three flavonoid glycosides including 2 new compounds (1-2) were
      isolated from Excoecaria agallocha as Hedgehog/GLI1-mediated transcriptional
      inhibitors and exhibited cytotoxicity against human pancreatic (PANC1) and
      prostate (DU145) cancer cells. Our data revealed that compound 1 clearly
      inhibited the expression of GLI-related proteins (PTCH and BCL-2) and blocked the
      translocation of GLI1 transcription factors into the nucleus in PANC1. Deleting
      the Smoothened (Smo) function in PANC1 treated with 1 led to downregulation of
      the mRNA expression of Ptch. This study describes the first Hh signaling
      inhibitor which blocks GLI1 movement into the nucleus without interfering with
      Smo.

PMID- 21190856
TI  - New azoles with antifungal activity: Design, synthesis, and molecular docking.
AB  - In order to search for many target compounds with excellent activities, a series
      of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluoro-phenyl)-3-[(4-substituted phenyl)
      piperazin-1-yl]-propan-2-ols were designed, synthesized, and evaluated as
      antifungal agents. Results of preliminary antifungal tests against eight human
      pathogenic fungi in vitro showed that all the title compounds exhibited excellent
      activities with broad spectrum. Moreover, a molecular model for the binding
      between 5a and the active site of CACYP51 was provided based on the computational
      docking results.

PMID- 21190857
TI  - Psammaplysin H, a new antimalarial bromotyrosine alkaloid from a marine sponge of
      the genus Pseudoceratina.
AB  - Mass-directed isolation of the CH(2)Cl(2)/CH(3)OH extract from a marine sponge of
      the genus Pseudoceratina resulted in the purification of a new antimalarial
      bromotyrosine alkaloid, psammaplysin H (1), along with the previously isolated
      analogs psammaplysins G (2) and F (3). The structure of 1 was elucidated
      following 1D and 2D NMR, and MS data analysis. All compounds were tested in vitro
      against the 3D7 line of Plasmodium falciparum and mammalian cell lines (HEK293
      and HepG2), with 1 having the most potent (IC(50) 0.41MUM) and selective (>97
      fold) antimalarial activity.

PMID- 21190858
TI  - Botulinum toxin A injections do not improve surface EMG patterns during gait in
      children with cerebral palsy--a randomized controlled study.
AB  - Children with cerebral palsy who walk with knee flexion during midstance are
      treated with intramuscular injections of botulinum toxin A (BTX-A) to prevent
      them from potential deterioration and to improve their mobility. The present
      study evaluates the effect of this treatment on the muscle activation patterns of
      the rectus femoris, medial hamstrings and gastrocnemius medialis during gait.
      Twenty-two children (aged 4-11 years) with cerebral palsy, who walked with knee
      flexion, were randomly assigned to an intervention group (multilevel BTX-A
      injections combined with comprehensive rehabilitation) or a control group (usual
      care). Sagittal and frontal video recordings were made of gait, together with
      simultaneous surface electromyography recordings of the rectus femoris, medial
      hamstring and gastrocnemius medialis muscles, before and six weeks after
      treatment. Abnormal muscle activation patterns were quantified, after gain
      normalisation, according to the root mean square difference (RMSD), which is the
      difference relative to normal patterns. Six weeks after the treatment the RMSD of
      the gastrocnemius medialis muscles in the intervention group changed
      significantly, showing a deterioration (p<0.05). This study demonstrated that BTX
      A injections do not result in an improvement in lower limb muscle activation
      patterns during gait. In spite of this lack of direct effect on muscle activation
      patterns, the combination of BTX-A injections and comprehensive rehabilitation
      was effective in improving gait kinematics.

PMID- 21190859
TI  - Discovery of novel phenylpyridone derivatives as potent and selective MCH1R
      antagonists.
AB  - The design, synthesis and structure-activity relationships of a novel class of N
      phenylpyridone MCH1R antagonists are described. The core part of the N
      phenylpyridone structure was newly designed and the side chain moieties that were
      attached to the core part were extensively explored. As a result of optimization
      of the N-phenylpyridone leads, we successfully developed the orally available,
      and brain-penetrable MCH1R selective antagonist 7c, exhibiting excellent anti
      obese effect in diet-induced obese (DIO) mice.

PMID- 21190860
TI  - Studies on 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-benzimidazole/2
      hydroxypropyl-beta-cyclodextrin association: Characterization, molecular modeling
      studies, and in vivo anthelminthic activity.
AB  - The purpose of this work is to study the molecular association that occurs
      between 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) and 6-chloro-5-(1
      naphthyloxy)-2-(trifluoromethyl)-1H-benzimidazole (RCB20), an antiparasitic
      compound recently found by our research group, with poor aqueous solubility. The
      complex stability constant and stoichiometric ratio determined by phase
      solubility diagram and Job's plot provided evidence that HPbetaCD enhanced water
      solubility of RCB20 through inclusion complex formation. Two-dimensional 1H NMR
      spectroscopy is used to study the molecular arrangement of inclusion complex in
      solution. These results are further supported using molecular modeling studies.
      In the solid state, the complexation is confirmed by differential scanning
      calorimetry, powder X-ray diffraction, and scanning electron microscopy. Finally,
      RCB20/HPbetaCD complex has better activity than RCB20 against the adult and
      muscle larvae phase of Trichinella spiralis.

PMID- 21190861
TI  - Synthesis, structure, theoretical and experimental in vitro
      antioxidant/pharmacological properties of alpha-aryl, N-alkyl nitrones, as
      potential agents for the treatment of cerebral ischemia.
AB  - The synthesis, structure, theoretical and experimental in vitro antioxidant
      properties using the DPPH, ORAC, and benzoic acid, as well as preliminary in
      vitro pharmacological activities of (Z)-alpha-aryl and heteroaryl N-alkyl
      nitrones 6-15, 18, 19, 21, and 23, is reported. In the in vitro antioxidant
      activity, for the DPPH radical test, only nitrones bearing free phenol groups
      gave the best RSA (%) values, nitrones 13 and 14 showing the highest values in
      this assay. In the ORAC analysis, the most potent radical scavenger was nitrone
      indole 21, followed by the N-benzyl benzene-type nitrones 10 and 15.
      Interestingly enough, the archetypal nitrone 7 (PBN) gave a low RSA value (1.4%)
      in the DPPH test, or was inactive in the ORAC assay. Concerning the ability to
      scavenge the hydroxyl radical, all the nitrones studied proved active in this
      experiment, showing high values in the 94-97% range, the most potent being
      nitrone 14. The theoretical calculations for the prediction of the antioxidant
      power, and the potential of ionization confirm that nitrones 9 and 10 are among
      the best compounds in electron transfer processes, a result that is also in good
      agreement with the experimental values in the DPPH assay. The calculated energy
      values for the reaction of ROS (hydroxyl, peroxyl) with the nitrones predict that
      the most favourable adduct-spin will take place between nitrones 9, 10, and 21, a
      fact that would be in agreement with their experimentally observed scavenger
      ability. The in vitro pharmacological analysis showed that the neuroprotective
      profile of the target molecules was in general low, with values ranging from 0%
      to 18.7%, in human neuroblastoma cells stressed with a mixture of
      rotenone/oligomycin-A, being nitrones 18, and 6-8 the most potent, as they show
      values in the range 24-18.4%.

PMID- 21190862
TI  - Reliability of the CFTM and GPA methods for strain analysis at ultra-thin layers.
AB  - The reliability of the Computational Fourier Transform Moire (CFTM) and Geometric
      Phase Analysis (GPA) techniques for strain analysis at ultra-thin layers has been
      investigated using computer-generated images. Our results revealed that the
      leakage effect creates error that is linearly dependent on the mask size used for
      Fourier filtering. Error due to the leakage effect has a significant impact on
      the analysis of strain for small-mismatched systems with low resolution in the
      original image. We demonstrate that the error due to the leakage effect can be
      minimized with improved resolution of the original image. In order to obtain a
      measurement of the reliability of the CFTM and GPA methods on ultra-thin layers,
      we systematically quantify the error due to the leakage effect as a function of
      image resolution and applied strain value for the original image. The presence of
      the leakage effect and the resulting limitations of the CFTM and GPA methods are
      demonstrated using a high-resolution transmission electron microscopy (HRTEM)
      image of an ultra-thin heterointerface from a strained layer superlattice.

PMID- 21190863
TI  - Ceramic nuclear fuel mechanical resistance development by means of dynamic impact
      testing.
AB  - In commercial reactors where a 'pellet missing surface' is observed a cladding
      crack has also been observed several times. Chips are produced mainly by dynamic
      impacts during pellet production process as a whole, i.e. emptying the sintering
      boats, pellets handling, vibration in the bowl feeder and grinding. At this work
      UO(2) chipping behavior was investigated and showed that pellets with higher
      density resist more to impacts and also that at the lowest impact angle tested
      the pellet weight loss was quite high.

PMID- 21190864
TI  - Seasonal changes in the excess energy dissipation from Photosystem II antennae in
      overwintering evergreen broad-leaved trees Quercus myrsinaefolia and Machilus
      thunbergii.
AB  - We monitored chlorophyll (Chl) fluorescence, pigment concentration and the de
      epoxidation state of the xanthophyll cycle (DPS(1)) in two warm temperate broad
      leaved evergreen species (Quercus myrsinaefolia and Machilus thunbergii).
      Reduction of the maximal quantum yield of Photosystem II (PSII) (calculated from
      Fv/Fm, variable to maximal Chl a fluorescence) and retention of a high DPS were
      observed in both species in the winter, and can be interpreted as acclimation to
      winter. In particular, the acclimation of PSII in these species can be chiefly
      attributed to thermal dissipation, which is correlated with the retention of high
      zeaxanthin. Furthermore, we attempted to divide the fate of the absorbed light
      energy by the PSII antennae into three components: (i) PSII photochemistry
      (represented by its quantum yield, PhiPSII), (ii) dissipation by down-regulation
      via non-photochemical quenching (PhiNPQ) and (iii) other non-photochemical
      processes (PhiONP). The estimated energy allocation of the absorbed light
      indicated that the proportion of PhiPSII decreased, whereas that of PhiNPQ+PhiONP
      increased during winter. This result suggests that the excess energy absorbed in
      the PSII complexes is safely dissipated from the PSII antennae. Based on these
      results, we conclude that thermal dissipation from the PSII antennae plays an
      important role in two overwintering broad-leaved evergreen trees growing in
      Japan.

PMID- 21190865
TI  - Increased serum TWEAK levels in Psoriatic arthritis: relationship with disease
      activity and matrix metalloproteinase-3 serum levels.
AB  - OBJECTIVES: We measured serum levels of Tumor necrosis factor (TNF)-like weak
      inducer of apoptosis (TWEAK), interleukin 15 (IL-15), monocyte chemoattractant
      protein 1 (MCP-1), and matrix metalloproteinase (MMP)-3 for patients with
      Psoriatic arthritis (PsA), and investigated whether TWEAK levels are associated
      with clinical disease activity and expression of proinflammatory cytokines.
      METHODS: Forty five patients with PsA and forty five patients with osteoarthritis
      (OA) were involved in this study between January 2008 and December 2009. At the
      time of blood sample collection, the disease activity of patients with PsA was
      assessed according to the 28-joint count Disease Activity Score (DAS28). Serum
      levels of TWEAK, IL-15, MCP-1, and MMP-3 were measured using commercial enzyme
      linked immunosorbent assay (ELISA) kits according to the manufacturers' protocol.
      RESULTS: In patients with PsA, serum TWEAK, IL-15, MCP-1 and MMP-3 levels were
      significantly elevated, and serum TWEAK levels showed a significant correlation
      with DAS28 (r=0.405, p=0.006) and serum MMP-3 levels (r=0.375, p=0.011).
      CONCLUSIONS: Serum TWEAK levels positively correlate with disease activity of PsA
      and confirm that TWEAK plays a crucial role in the pathogenesis of PsA. TWEAK may
      be a new important target for therapy in PsA.

PMID- 21190866
TI  - Involvement of endogenous hydrogen sulfide in cigarette smoke-induced changes in
      airway responsiveness and inflammation of rat lung.
AB  - Hydrogen sulfide (H2S), recently considered the third endogenous gaseous
      transmitter, may have an important role in systemic inflammation. We investigated
      whether endogenous H2S may be a crucial mediator in airway responsiveness and
      airway inflammation in a rat model of chronic exposure to cigarette smoke (CS).
      Rats randomly divided into control and CS-exposed groups were treated with or
      without sodium hydrosulfide (NaHS, donor of H2S) or propargylglycine (PPG,
      inhibitor of cystathionine-gamma-lyase [CSE], an H2S-synthesizing enzyme) for 4
      month exposure. Serum H2S level and CSE protein expression in lung tissue were
      higher, by 2.04- and 2.33-fold, respectively, in CS-exposed rats than in controls
      (P<0.05). Exogenous administration of NaHS to CS-exposed rats alleviated airway
      reactivity induced by acetylcholine (Ach) or potassium chloride (KCl) by 17.4%
      and 13.8%, respectively, decreased lung pathology score by 32.7%, inhibited IL-8
      and TNF- alpha concentrations in lung tissue by 34.2% and 31.4%, respectively, as
      compared with CS-exposed rats (all P<0.05). However, blocking endogenous CSE with
      PPG in CS-exposed rats increased airway reactivity induced by Ach or KCl, by
      24.1% and 24.5%, respectively, and aggravated lung pathology score, by 44.8%, as
      compared with CS-exposed rats (all P<0.01). Incubation in vitro with NaHS, 1-3
      mmol/L, relaxed rat tracheal smooth muscle precontracted by Ach or KCl. However,
      the NaHS-induced relaxation was not blocked by glibenclamide (10-4 mol/L), L-NAME
      (10-4 mol/L), or ODQ (1 MUmol/L) or denudation of epithelium. Endogenous H2S may
      have a protective role of anti-inflammation and bronchodilation in chronic CS
      induced pulmonary injury.

PMID- 21190868
TI  - Interleukin-6 as an independent predictor of future cardiovascular events in high
      risk Japanese patients: comparison with C-reactive protein.
AB  - Inflammation is associated with the development of atherosclerotic vascular
      lesions and some inflammatory parameters are used as cardiovascular (CV) risk
      markers. The present study was designed to assess the predictive power of
      interleukin (IL)-6 for future CV events. In 121 Japanese patients with multiple
      CV risk factors and/or disease, serum concentrations of IL-6 and high sensitive C
      reactive protein (hs-CRP) were measured. During follow-up periods (mean, 2.9
      years) after the baseline assessment, 50 patients newly experienced CV events
      such as stroke/transient ischemic attack (n=10), heart failure hospitalization
      (n=6), acute coronary syndrome (n=7), and revascularization for coronary artery
      disease (n=15) and peripheral arterial disease (n=12). The serum level of IL-6,
      but not hs-CRP, was significantly higher in patients who had CV events than in
      event-free subjects (3.9+/-2.6 and 3.0+/-2.2 pg/mL, P=0.04). When the patients
      were divided into three groups by tertiles of basal levels of IL-6 (<1.85, 1.85
      3.77, and >=3.77 pg/mL), cumulative event-free rates by the Kaplan-Meier method
      were decreased according to the increase in basal IL-6 levels (65%, 50%, and 19%
      in the lowest, middle, and highest tertiles of IL-6, respectively; log-rank test,
      P=0.002). By univariate Cox regression analysis, previous CV disease, creatinine
      clearance, and serum IL-6 levels were significantly associated with CV events
      during follow-up. Among these possible predictors, the highest tertile of IL-6
      was only an independent determinant for the morbidity in the multivariate
      analysis (hazard ratio 2.80 vs. lowest tertile, P=0.006). These findings indicate
      that IL-6 is a powerful independent predictor of future CV events in high-risk
      Japanese patients, suggesting its predictive value is superior to that of hs-CRP.

PMID- 21190867
TI  - IL-33 is expressed in human osteoblasts, but has no direct effect on bone
      remodeling.
AB  - The aim of the present study was to investigate the potential role of the
      recently discovered IL-1 family member IL-33 in bone remodeling. Our results
      indicate that IL-33 mRNA is expressed in osteocytes in non-inflammatory human
      bone. Moreover, IL-33 levels are increased by TNF-alpha and IL-1beta in human
      bone marrow stromal cells, osteoblasts and adipocytes obtained from three healthy
      donors. Experiments with the inhibitor GW-9662 suggested that expression of IL
      33, in contrast to that of IL-1beta, is not repressed by PPARgamma likely
      explaining why IL-33, but not IL-1beta, is expressed in adipocytes. The IL-33
      receptor ST2L is not constitutively expressed in human bone marrow stromal cells,
      osteoblasts or CD14-positive monocytes, and IL-33 has no effect on these cells.
      In addition, although ST2L mRNA is induced by TNF-alpha and IL-1beta in bone
      marrow stromal cells, IL-33 has the same effects as TNF-alpha and IL-1beta, and,
      therefore, the biological activity of IL-33 may be redundant in this system. In
      agreement with this hypothesis, MC3T3-E1 osteoblast-like cells constitutively
      express ST2L mRNA, and IL-33 and TNF-alpha/IL-1beta similarly decrease
      osteocalcin RNA levels in these cells. In conclusion, our results suggest that IL
      33 has no direct effects on normal bone remodeling.

PMID- 21190869
TI  - The tickly homunculus and the origins of spontaneous sensations arising on the
      hands.
AB  - Everyone has felt those tingling, tickly sensations occurring spontaneously all
      over the body in the absence of stimuli. But does anyone know where they come
      from? Here, right-handed subjects were asked to focus on one hand while looking
      at it (convergent focusing) and while looking away (divergent focusing) and
      subsequently to map and describe the spatial and qualitative attributes of
      sensations arising spontaneously. The spatial distribution of spontaneous
      sensations followed a proximo-distal gradient, similar to the one previously
      described for the density of receptive units. The intensity and spatial extent of
      the reported sensations were modulated by the focusing condition, especially in
      respect of the left hand. Convergent focusing acted upon the conscious perception
      of sensations by enhancing or suppressing them. To our knowledge, this is the
      first ever study of spontaneous sensations, and it offers considerable insight
      into their sources. The presence of the proximo-distal distributional gradient is
      a clear sign that receptive units are involved. The enhancement/suppression
      effects also confirm the involvement of attention. Finally, left-hand dominance
      suggests several right-hemisphere processes may be involved, such as spatial and
      tactile perception, and probably interoception.

PMID- 21190870
TI  - Application of MLPA assay to characterize unsolved alpha-globin gene
      rearrangements.
AB  - alpha-thalassemia belongs to those inherited diseases in which large genomic
      deletions/duplications represent a significant proportion of causative mutations.
      Until recently, large alpha-globin gene cluster rearrangements have been mainly
      detected by gap-PCR and Southern blotting, methods that have significant
      drawbacks. We tested the recently developed multiplex ligation-dependent probe
      amplification (MLPA) assay for deletional screening of the alpha-globin gene
      cluster in a cohort of 25 individuals suspected of having alpha-globin
      alteration(s), in which no or doubtful mutations had been found using
      conventional methods. In 13 out of 18 alpha-thalassemia carriers and in all 5
      patients with HbH we found the causative alpha-globin defects. In 2 thalassemia
      intermedia patients, carriers of heterozygous beta-globin mutations, the co
      inheritance of homozygous alpha-genes triplication was detected. MLPA results
      were subsequently confirmed by real-time PCR. This study shows that MLPA can
      effectively identify different and unknown types of alpha-globin gene
      rearrangements, to allow characterizing previously unsolved alpha-thalassemia
      genotypes.

PMID- 21190871
TI  - Pubertal delay, hypokalemia, and hypertension caused by a rare form of congenital
      adrenal hyperplasia.
AB  - A 17-year-old female presented with diffuse muscle weakness secondary to severe
      hypokalemia, metabolic alkalosis, and hypertension. Additional findings included
      delayed puberty with primary amenorrhea. Laboratory evaluation led to a diagnosis
      of 17 alpha-hydroxylase/17,20-lyase (P450c17) deficiency, a form of congenital
      adrenal hyperplasia (CAH). Her symptoms and metabolic derangements improved with
      glucocorticoid replacement to suppress ACTH production and mineralocorticoid
      excess, although she continues to require antihypertensive therapy. Estrogen
      replacement was initiated due to sex hormone insufficiency. This rare disorder
      should be considered when evaluating patients with pubertal delay and
      hypertension, particularly if there is associated hypokalemia.

PMID- 21190872
TI  - Sexpectations: male college students' views about displayed sexual references on
      females' social networking web sites.
AB  - STUDY OBJECTIVE: Sexual reference display on a social networking web site (SNS)
      is associated with self-reported sexual intention; females are more likely to
      display sexually explicit content on SNSs. The purpose of this study was to
      investigate male college students' views towards sexual references displayed on
      publicly available SNSs by females. DESIGN: Focus groups. SETTING: One large
      state university. PARTICIPANTS: Male college students age 18-23. INTERVENTIONS:
      All tape recorded discussion was fully transcribed, then discussed to determine
      thematic consensus. MAIN OUTCOME MEASURES: A trained male facilitator asked
      participants about views on sexual references displayed on SNSs by female peers
      and showed examples of sexual references from female's SNS profiles to facilitate
      discussion. RESULTS: A total of 28 heterosexual male participants participated in
      seven focus groups. Nearly all participants reported using Facebook to evaluate
      potential female partners. Three themes emerged from our data. First,
      participants reported that displays of sexual references on social networking web
      sites increased sexual expectations. Second, sexual reference display decreased
      interest in pursuing a dating relationship. Third, SNS data was acknowledged as
      imperfect but valuable. CONCLUSION: Females who display sexual references on
      publicly available SNS profiles may be influencing potential partners' sexual
      expectations and dating intentions. Future research should examine females'
      motivations and beliefs about displaying such references and educate women about
      the potential impact of these sexual displays.

PMID- 21190873
TI  - Serum adiponectin levels in high school girls with polycystic ovary syndrome and
      hyperandrogenism.
AB  - OBJECTIVE: To compare the serum adiponectin levels together with metabolic and
      hormonal parameters among teenage girls at the early onset of polycystic ovary
      syndrome (PCOS) and hyperandrogenism with controls. DESIGN: Prospective study.
      SETTINGS: Education and research hospital, outpatient gynecological endocrinology
      clinic. PARTICIPANTS: Four hundred seventy-nine teenage girls from a school of
      nursing were interviewed for the signs and symptoms of PCOS. Among them, 42 cases
      who had a definitive diagnosis of PCOS with hyperandrogenism based on Rotterdam
      diagnostic criteria were recruited for the study and other causes of
      hyperandrogenemia had been excluded. The controls were recruited from regularly
      cycling healthy teenage girls from the same high school of nursing; none of those
      who agreed to join the study met any of the diagnostic criteria for PCOS (n =
      44). INTERVENTIONS: Cases were selected as group I: PCOS with body mass index
      (BMI) < 25 kg/m2 (n = 20), group II: PCOS with BMI > 25 kg/m2 (n = 22), group
      III: Controls with BMI < 25 kg/m2 (n = 21) and group IV: Controls with BMI > 25
      kg/m2 (n = 23). Serum adiponectin, metabolic and hormonal parameters were
      compared in PCOS patients with BMI matched controls. MAIN OUTCOME MEASURES:
      Difference of serum adiponectin levels, metabolic and hormonal parameters between
      teenage girls with PCOS and controls. RESULTS: Serum adiponectin levels were not
      significantly different in group I and group II. Serum adiponectin levels were
      significantly decreased in group I and group II compared with both control groups
      (III and IV). CONCLUSION: Serum adiponectin levels were lower in teenage girls
      with PCOS and this reduction was independent from BMI.

PMID- 21190874
TI  - Ovarian dermoid cyst super-infected with methicillin-sensitive Staphylococcus
      aureus leading to the misdiagnosis of appendicitis in an adolescent.
AB  - BACKGROUND: Mature cystic teratomas (dermoid cysts) are the most common ovarian
      tumor in adolescents. Super-infection of a dermoid cyst is a rare event usually
      associated with a concomitant infection. CASE: A 14-year-old female was
      transferred to our institution with five days of fevers and abdominal pain. CT of
      the abdomen/pelvis was read as acute appendicitis with a 7.6 cm right adnexal
      dermoid cyst. The patient was treated for appendicitis but later found to have an
      infected dermoid cyst primarily infected with methicillin-sensitive
      staphylococcus aureus, which led the misdiagnosis of appendicitis. SUMMARY AND
      CONCLUSION: Super-infection of an ovarian dermoid cyst is an extremely rare
      event. We recommend that previously described evaluation, surgical management,
      and ovarian conservation be employed in all cases of ovarian dermoid cysts.

PMID- 21190875
TI  - Bleeding disorder education in obstetrics and gynecology residency training: a
      national survey.
AB  - STUDY OBJECTIVE: The purpose of this study was to assess the educational approach
      to the bleeding disorder evaluation in Obstetrics and Gynecology residency
      training programs in the continental United States. Information was sought from
      chief residents regarding training experiences and fund of knowledge regarding
      the evaluation of menorrhagia and diagnosis of bleeding disorders during their
      residency. DESIGN: A 24-item questionnaire was sent to the chief residents at 241
      non-military Obstetrics and Gynecology residency programs. SETTING: The study was
      conducted at Texas Children's Health Plan in Houston, Texas. PARTICIPANTS: Chief
      residents at 241 non-military Obstetrics and Gynecology residency programs. MAIN
      OUTCOME MEASURES: Responses to questionnaires. RESULTS: The overall response rate
      was 30%. Residents reported training in the medical evaluation of menorrhagia
      during residency with a mean of 9.1 hours per year in the first year of residency
      and 11.1 hours/year in the 2(nd), 3(rd) and 4(th) years; 67.7% reported they
      viewed their training in the medical evaluation of menorrhagia and bleeding
      disorders as sufficient preparation for clinical practice; and over two thirds
      reported specific training in common bleeding disorders, such as von Willebrand
      disease. CONCLUSION: The current state of training in the evaluation of
      menorrhagia and bleeding disorders appeared to be mixed regarding the evaluation
      of dysfunctional uterine bleeding. An area for improvement was identified to
      better approach best clinical practice in the evaluation of women with
      menorrhagia and underlying bleeding disorders, which can be guided by the
      thoughtful approach taken in the recent NHLBI von Willebrand disease guidelines.

PMID- 21190876
TI  - Recurrent menorrhagia in an adolescent with a platelet secretion defect.
AB  - BACKGROUND: Although von Willebrand disease is the most common inherited bleeding
      disorder, platelet function disorders are less well recognized as a cause of
      bleeding. We report a case of menorrhagia caused by an unsuspected platelet
      secretion defect. CASE: A 13-year-old Asian female, with unknown family history,
      presented with menorrhagia not responsive to intravenous conjugated estrogens,
      requiring transfusion of 7 units of packed red blood cells. Initial screening
      tests for bleeding disorders were normal; however, due to high clinical
      suspicion, further specific testing with platelet aggregometry was performed,
      which revealed a platelet secretion defect. SUMMARY AND CONCLUSION: The
      prevalence of platelet secretion defects in adolescents with menorrhagia is
      unknown, but may be higher than currently recognized. When screening tests are
      normal, yet suspicion remains high for an underlying hemostatic disorder,
      platelet aggregometry must be performed.

PMID- 21190877
TI  - Management of sexual assault-related large rectovaginal fistula in an eight-year
      old.
AB  - Rectovaginal fistula may be a complication sexual assault in children. Management
      of these cases could be daunting with possibilities of significant psychological
      and physical morbidity. An eight-year-old girl presented with vulvar fecal
      leakage from a large rectovaginal fistula two weeks after sexual assault. The
      child was managed by initial diverting colostomy and the fistula repair was
      carried out via a posterior sagittal approach. This report highlights
      significance of initial thorough evaluation in cases with suspected traumatic
      rectovaginal fistula, and demonstrates benefits of posterior sagittal approach in
      the definitive treatment of large-sized fistula.

PMID- 21190878
TI  - An 8.9 year old girl with autism and Gorlin syndrome.
AB  - We present an 8.9 year old girl diagnosed with autism and macrocrania. Because of
      macrocrania, hypertelorism and epidermal punctiform lesions in the palm of the
      hand, Gorlin syndrome was clinically suspected and molecularly confirmed by
      finding a deletion of 22 base pairs in the PTCH1 gene. The possibility of an
      association between autism and Gorlin syndrome is discussed.

PMID- 21190879
TI  - Epidemiology and correlation of the clinicopathological features in oral
      epithelial dysplasia: analysis of 173 cases.
AB  - Oral epithelial dysplasias (OEDs) are potentially malignant disorders
      characterized by diverse degrees of cellular atypia. The early and careful
      diagnosis has extreme importance, allowing prevention of the progression to the
      oral squamous cell carcinoma. This study aimed to determine the epidemiology and
      then correlate it with the clinicopathological features of OED. One hundred
      seventy-three cases of oral lesions retrieved from the files of a Service of
      Pathological Anatomy, covering a 38-year period, were submitted to descriptive
      statistical analysis through the Pearson chi(2) test. The majority of cases were
      from affected females (57.9%), with a peak of occurrence in the age group of 41
      and 55 years (37.3%), white patients (64.8%), and those with lesions located on
      the gingiva/alveolar ridge (25.1%). The lesions predominantly presented with
      white color (56.8%) and were described as nodules (27.4%), with a rough surface
      (76.7%), an exophytic growth (79.1%), and a sessile base (95.6%). The majority of
      the lesions with degree of mild (34.6%) and moderate (34.9%) OED had clinical
      diagnosis of leukoplakia, whereas 33.3% of the lesions with degree of severe had
      clinical diagnosis of squamous cell carcinoma (P < .05). Tobacco use was the risk
      habit more related with OED (42.6%) (P > .05). The knowledge of OED epidemiology
      and clinical features provide a better understanding of the factors that possibly
      are associated with the malignant transformation of OED. Furthermore, these
      results contribute to supporting a prompt and accurate recognition of these
      lesions in clinical practice.

PMID- 21190880
TI  - Cutaneous angiosarcoma. Analysis of 434 cases from the Surveillance,
      Epidemiology, and End Results Program, 1973-2007.
AB  - Cutaneous angiosarcoma is an aggressive malignant mesenchymal vasoformative
      neoplasm that accounts for 1% of all soft tissue sarcomas. Using data from the
      National Cancer Institute's Surveillance, Epidemiology, and End Results program,
      we analyzed the demographics and survival of cutaneous angiosarcoma. The
      Surveillance, Epidemiology, and End Results program recorded 434 cases of
      cutaneous angiosarcoma from 1973 to 2007. The incidence was nearly the same in
      men (222 cases) and women (212 cases). Most patients were white (88%) with a mean
      age of 73 years. African Americans made up only 4% of the cases. Two hundred
      seventy (62%) cases were tumors of the head and neck, whereas 106 (24%) cases
      arose in the skin of the trunk. Grade was recorded in 194 cases (45%): 28 were
      grade I, 44 were grade II, 60 were grade III, and 62 were grade IV. Survival
      rates of cutaneous angiosarcoma correlated with age, anatomical site, and stage
      of disease. Patients younger than 50 years had a 10-year relative survival rate
      of 71.7%, whereas patients 50 years and older had a 36.8% 10-year survival rate.
      Tumors of the scalp and neck resulted in a 13.8% 10-year relative survival rate,
      whereas tumors arising in the trunk resulted in a 75.3% 10-year survival rate.
      Tumors localized to the skin had better prognosis (53.6% 10-year relative
      survival rate) than those with regional or distant stage (19.0% and 6.2%). Twenty
      six percent of patients with angiosarcoma had a prior primary. Cutaneous
      angiosarcomas arise predominantly in the head and neck of white individuals older
      than 60 years.

PMID- 21190882
TI  - Storage alters feline bronchoalveolar lavage fluid cytological analysis.
AB  - Bronchoalveolar lavage fluid (BALF) collection is a valuable respiratory
      diagnostic procedure in cats. This study evaluated effects of BALF storage on
      total nucleated cell counts (TNCCs) and differential cell counts (DCC), cell
      morphology, and cytological diagnosis. Forty-five research cats with
      neutrophilic, eosinophilic, and mixed inflammation, and healthy controls were
      enrolled. BALF samples were processed within 1h (baseline) or stored at 4 degrees
      C (4C24) or room temperature (RT24) for 24h, or 4 degrees C (4C48) or room
      temperature (RT48) for 48h before processing. Stored BALF at RT48 had decreased
      TNCC compared to baseline. The RT24 and RT48 samples had greater eosinophil % and
      the RT24, 4C48, and RT48 samples had decreased neutrophil % compared with
      baseline. Cellular morphology deteriorated in all stored samples. Storage
      resulted in a change in cytological diagnosis in up to 57% of stored samples. We
      conclude that cytological analysis of BALF in cats should be performed promptly
      for optimal results.

PMID- 21190881
TI  - Induction of PDK4 in the heart muscle of JVS mice, an animal model of systemic
      carnitine deficiency, does not appear to reduce glucose utilization by the heart.
AB  - Pyruvate dehydrogenase kinase 4 (PDK4) mRNA has been reported as an up-regulated
      gene in the heart and skeletal muscle of carnitine-deficient juvenile visceral
      steatosis (JVS) mice under fed conditions. PDK4 plays an important role in the
      inhibition of glucose oxidation via the phosphorylation of pyruvate dehydrogenase
      complex (PDC). This study evaluated the meaning of increased PDK4 mRNA in glucose
      metabolism by investigating PDK4 protein levels, PDC activity and glucose uptake
      by the heart and skeletal muscle of JVS mice. PDK4 protein levels in the heart
      and skeletal muscle of fed JVS mice were increased in accordance with mRNA
      levels, and protein was enriched in the mitochondria. PDK4 protein was co
      fractionated with PDC in sucrose density gradient centrifugation, like PDK2
      protein; however, the activities of the pyruvate dehydrogenase complex (PDC)
      active form in the heart and skeletal muscle of fed JVS mice were similar to
      those in fed control mice. Fed JVS mice showed significantly higher glucose
      uptake in the heart and similar uptake in the skeletal muscle compared with fed
      control mice. Thus, in carnitine deficiency under fed conditions, glucose was
      preferentially utilized in the heart as an energy source despite increased PDK4
      protein levels in the mitochondria. The preferred glucose utilization may be
      involved in developing cardiac hypertrophy from carnitine deficiency in fatty
      acid oxidation abnormality.

PMID- 21190883
TI  - Implications of hepatitis C viremia vs. antibody alone on transmission among male
      injecting drug users in three Afghan cities.
AB  - OBJECTIVES: To assess differences between injecting drug users (IDUs) with
      hepatitis C virus (HCV) viremia and IDUs with HCV antibody (Ab) or no evidence of
      prior infection in three Afghan cities. METHODS: IDUs in Hirat, Jalalabad, and
      Mazar-i-Sharif completed questionnaires and rapid testing for blood-borne
      infections including HCV Ab. HCV Ab was confirmed with a recombinant immunoblot
      assay (RIBA); RIBA-positive specimens underwent reverse transcriptase polymerase
      chain reaction (RT-PCR) for HCV. Risk behaviors associated with viremia were
      assessed with site-controlled ordinal regression analysis. RESULTS: Of 609
      participants, 223 (36.6%) had confirmed HCV Ab. Of 221 with serum available for
      PCR evaluation, 127 (57.5%) were viremic. HCV viremia prevalence did not differ
      by site (range 41.7-59.1%; p=0.52). Among all IDUs, in age and site-controlled
      ordinal regression analysis, HCV was independently associated with HIV co
      infection (adjusted odds ratio (AOR) 7.16, 95% confidence interval (CI) 4.41
      11.64), prior addiction treatment (AOR 1.95, 95% CI 1.57-2.42), ever aspirating
      and re-injecting blood (AOR 1.62, 95% CI 1.18-2.23), prior incarceration (AOR
      1.60, 95% CI 1.04-2.45), and sharing injecting equipment in the last 6 months
      (AOR 1.35, 95% CI 1.02-1.80). CONCLUSION: HCV viremia was present in many
      participants with prior HCV infection and was associated with some injecting risk
      behaviors, indicating a substantial risk for transmission. Current harm reduction
      programs should aim to improve HCV awareness and prevention among IDUs in
      Afghanistan as a matter of urgency.

PMID- 21190884
TI  - [Fetal RHD genotyping by PCR using plasma from D negative pregnant women].
AB  - AIM OF THE STUDY: Free fetal DNA in maternal blood offers a non invasive method
      for prenatal diagnosis. The aim of this study is to perform fetal RHD genotyping
      by conventional PCR in D negative pregnant women of Moroccan origin. PATIENTS AND
      METHODS: Plasma sample from 120 D negative pregnant women from 10 to 40
      gestational weeks were tested by conventional PCR for the presence of exons 7 and
      10 of RHD gene. The results were compared with the RhD phenotype of the newborns.
      RESULTS: In this study, the positive and the negative predictive value of the
      fetal RhD status were 98.7 and 96.7%, respectively. CONCLUSION: These results
      demonstrate de feasibility of fetal RHD genotyping by conventional PCR in D
      negative pregnant women of Moroccan origin.

PMID- 21190885
TI  - Prevalence of type 2 diabetes and other cardiovascular risk factors in Mayotte in
      2008: the MAYDIA study.
AB  - AIM: Mayotte, a French overseas territory located in the Indian Ocean, has never
      had a previous estimate of diabetes prevalence, but has recently undergone
      socioeconomic changes leading to lifestyle modifications. For this reason, a
      survey was carried out in 2008 to estimate the prevalence of diabetes and
      cardiovascular risk factors in the island's population. METHODS: A three-step,
      randomized sample of 1268 individuals, aged 30-69 years, was home-screened, using
      capillary blood glucose and capillary HbA(1c), weight, height, waist
      circumference and two blood-pressure measurements. Those with a history of
      diabetes, glucose >=1 g/L (fasting) or >=1.40 g/L (non-fasting), or HbA(1c)>=6%,
      and a subgroup of those with normal results were examined at a healthcare centre
      to measure venous HbA(1c) and glucose, and to diagnose diabetes, using an oral
      glucose tolerance test. RESULTS: The weighted prevalence of diabetes (venous
      plasma glucose >=1.26 g/L at fasting and/or >=2 g/L at 2 h, or treatment with
      oral hypoglycaemic agents or insulin) was 10.5% (95% CI: 8.2-13.4%). This
      increased with age from 3% at age 30-39 years to 26% at age 60-69 years, with no
      gender differences. Also, more than 50% of those with diabetes were unaware of
      it, while half of those treated for diabetes still had HbA(1c) levels >7%. The
      prevalence of overweight (BMI: 25-29 kg/m(2)) was estimated to be 35% in men and
      32% in women, while obesity (>=30 kg/m(2)) was estimated to be 17% in men and 47%
      in women. CONCLUSION: The high prevalence of obesity combined with a high
      prevalence of diabetes indicates a potential for further increases in the
      prevalence of diabetes and cardiovascular disease in Mayotte. Preventative action
      against obesity, diabetes and hypertension is required now, as well as plans for
      appropriate healthcare delivery in the island.

PMID- 21190886
TI  - [Uterine lipoma: A case report probably due to a surgical traumatism].
AB  - Uterine lipomas are uncommon. Several histology hypotheses are described.
      Ultrasound is firstly performed but diagnosis is sometimes difficult. Magnetic
      resonance imaging is more specific and helpful to make a differential diagnosis
      with a dermoid ovarian cyst. Despite those imaging exams we detail a case of a
      patient where a laparoscopic hysterectomy with bilateral salpingo-oophorectomy
      and preliminary adhesiolysis has been necessary to establish diagnosis. Among her
      medical history some previous abdominal surgeries could be the cause of this
      lesion.

PMID- 21190888
TI  - Large-scale ultrasonic cleaning system: Design of a multi-transducer device for
      boat cleaning (20kHz).
AB  - The present study is part of a global project which consists in the development
      of an automatic cleaning station for immersed boats (cockle, ninepin, etc.) in a
      self-service mode, associating an innovative ultrasonic device for cleaning with
      a specific water treatment. The originality of the process is that cleaning is
      performed by three transducers operating simultaneously at low frequency and
      moving along the surface, thanks to programmable logic controllers, and that it
      includes a suction to collect the dirt removed. Therefore, the time required for
      boat maintenance is shortened, ensuring high quality cleaning without the need
      for dry docks and avoiding additional pollution in the harbor areas. One of the
      key points was the evaluation of washing efficiency, as it is really hard to give
      a quantitative estimation of the dirt removed. To obtain the first design laws,
      feasibility tests have been carried out on dirty cockle samples and on real boat
      hulls with a laboratory ultrasonic device. The influence of a large number of
      parameters was tested such as transducer-probe distance, displacement speed and
      transmitted power. The obtained data allowed us to design an optimized cleaning
      device combining high efficiency and speed.

PMID- 21190887
TI  - Removal of dinitrotoluenes and trinitrotoluene from industrial wastewater by
      ultrasound enhanced with titanium dioxide.
AB  - Oxidative degradation of dinitrotoluenes (DNTs) and 2,4,6-trinitrotoluene (TNT)
      in wastewater was conducted using ultrasonic irradiation combined with titanium
      dioxide (TiO(2)). The batch-wise experiments were carried out to elucidate the
      influence of various operating parameters on the sonolytic behavior, including
      power intensity, TiO(2) dosage, acidity of wastewater, reaction temperature and
      oxygen dosage. It is worthy to note that the nitrotoluene contaminants could be
      almost completely eliminated by sonochemical oxidation enhanced significantly
      with the addition of TiO(2) due to the supply of adsorbent and/or excess nuclei.
      High destruction rate of nitrotoluenes could be achieved by increasing the
      acidity of wastewater and decreasing the reaction temperature. According to the
      result given by pyrolysis/gas chromatograph-mass spectrometer (Pyrolysis/GC-MS),
      it is postulated that DNTs adsorbed on TiO(2) preliminarily undergo denitration
      pathway to o-mononitrotoluene (MNT) or oxidation pathway to 1,3-dinitrobenzene
      (DNB), respectively. Further, based on the spectra obtained from GC-MS, it is
      proposed that DNTs dissolved in wastewater proceed with similar reaction pathways
      as those adsorbed on TiO(2). Besides, oxidative degradation of 2,4,6-TNT results
      in the formation of 1,3,5-trinitrobenzene (TNB). Apparently, the sonolytic
      technique established is promising for direct treatment of wastewater from TNT
      manufacturing process.

PMID- 21190889
TI  - Effect of reaction conditions on size and morphology of ultrasonically prepared
      Ni(OH)(2) powders.
AB  - Modern electrochemical devices require the morphological control of the active
      material. In this paper the synthesis of nickel hydroxide, as common active
      compound of such devices, is presented. The influence of ultrasound in the
      synthesis of nickel hydroxide from aqueous ammonia complexes is studied showing
      that ultrasound allows the fabrication of flower-like particles with sizes
      ranging in between 0.7 and 1.0MUm in contrast with the 6-8MUm particles obtained
      in the absence of ultrasound. The influence of gas flow, temperature of the
      process and surfactants in the ultrasonically prepared powders is discussed in
      term of shape, size and agglomeration of the particles. Adjusting the
      experimental condition, spherical or platelet-like particles are obtained with
      sizes ranging from 1.3MUm to 200nm.

PMID- 21190891
TI  - Potential of hydrogen bond in water. Comparison of the theory with vibrational
      spectra and results of molecular dynamics simulations.
AB  - Potential of hydrogen bond is the function which relates its energy to
      geometrical parameters of hydrogen bridge: its length R(O...O) and angles between
      direction O...O and OH group [phi (H-O...O)] and/or lone pair of proton accepting
      oxygen atom [chi(-O...O)]. Previously we have suggested an approach to design
      such potentials based on the approximate numerical solution of a reverse problem
      of the spectrum band shape in the frames of the fluctuation theory of hydrogen
      bonding. In the given work this method is applied to construction of the two
      parameter potentials that depend on parameters {R(O...O), phi (H-O...O} or {phi
      (H-O...O), chi (-O...O)}. Using them, the spectra of OH vibrations of HOD
      molecules in a liquid phase are calculated theoretically in good agreement with
      experiment in the temperature range up to 200  degrees C. Distributions of angles
      P(phi, T), P(chi, T), and energies P(E) are calculated also. The same
      distributions and spectra are independently calculated on the basis of the
      geometrical parameters of the hydrogen bridges obtained from molecular dynamics
      models of water. The shapes of the spectral contours and their temperature
      evolution calculated for computer models turned out to be similar to experimental
      ones only for the potential that includes the length of H-bond R(O...O).

PMID- 21190890
TI  - The effects of 2 week senofilcon-A silicone hydrogel contact lens daily wear on
      tear functions and ocular surface health status.
AB  - PURPOSE: To prospectively investigate the effects of 2 week senofilcon A contact
      lens (CL) daily wear on the functional visual acuity (VA), ocular surface and
      tear film. METHODS: Seventeen right eyes of 17 senofilcon A CL wearers without
      any ocular or systemic diseases were examined before and 2 weeks after lens wear.
      Visual acuity measurements, tear evaporation rate, ELISA for tear cytokines,
      strip meniscometry, tear lipid layer interferometry, tear film break-up time
      (BUT), in vivo confocal microscopy, corneal sensitivity, ocular surface vital
      staining, Schirmer I test and brush cytology for MUC5AC mRNA expression were
      performed before and after CL wear. RESULTS: The best corrected Landolt VA,
      functional VA parameters, the mean lipid layer interferometry grades, tear
      evaporation rates, Schirmer test values, vital staining scores and in vivo
      confocal microscopy parameters did not show any significant differences after 2
      weeks of CL wear. The tear film BUT showed a significant decrease together with a
      significant down regulation of MUC5 AC mRNA expression after CL wear. A
      statistically significant elevation in the mean tear interleukin (IL)-6
      concentration was also observed after 2 weeks of CL wear. CONCLUSIONS: Two week
      senofilcon A daily CL wear seems to be associated with tear instability, a
      decrease in MUC5AC expression, and elevation of IL-6 in tears without significant
      alterations in epithelial damage scores or in the morphology or density of in
      vivo keratoconjunctival cells and nerves. Alterations associated with long term
      wear and patients with dry eye disease need to be studied in future trials.

PMID- 21190892
TI  - Examination of cellulose textile fibres in historical objects by micro-Raman
      spectroscopy.
AB  - The investigation and characterisation of historical objects can be an exacting
      piece of work because of the small quantity of material that can be investigated
      and the degradation of the material and its value, which sometimes demands only
      non-destructive methods. In this study, as one such method, Raman spectroscopy
      was used to investigate the cellulose fibres of painting canvases and linings.
      Historical samples of fabrics were taken from different paintings and their
      linings from different locations in Slovenia. Raman spectra were recorded on the
      fibres of these historical samples. Additionally, a database of the Raman spectra
      of modern cellulose fibres was created and compared with the literature data.
      Differences in the Raman spectra of different cellulose fibres were observed, and
      on this basis fibres of different types were discriminated. The recorded Raman
      spectra of historical samples were compared with the database spectra of modern
      cellulose fibres. Strong luminescence effects because of the changes caused by
      ageing, degradation products and surface contamination caused difficulties in
      interpreting the Raman spectra of historical fibres. The luminescence effects
      were partly overcome by prolonged exposition times and previous "signal
      quenching" with the laser. The Raman spectra of historical cotton showed no
      luminescence effects, and only slight differences to the reference spectra of
      modern cotton fibres appeared, whereas the Raman spectra of historical flax
      fibres were overwhelmed with luminescence and showed changes in spectra through
      degradation. The research showed that by using Raman spectroscopy the
      identification and differentiation of different cellulose fibres and materials
      that accompany cellulose in the fibres are possible and that degraded and aged
      material can be differentiated.

PMID- 21190893
TI  - Surface-enhanced Raman scattering of a Ag/oligo(phenyleneethynylene)/Ag sandwich.
AB  - alpha,omega-Dithiols are a useful class of compounds in molecular electronics
      because of their ability to easily adsorb to two metal surfaces, producing a
      molecular junction. We have prepared Ag nanosphere/oligo(phenyleneethynylene)/Ag
      sol (AgNS/OPE/Ag sol) and Ag nanowire/oligo(phenyleneethynylene)/Ag sol
      (AgNW/OPE/Ag sol) sandwiches to simulate the architecture of a molecular
      electronic device. This was achieved by self-assembly of OPE on the silver
      nanosurface, deprotection of the terminal sulfur, and deposition of Ag sol atop
      the monolayer. These sandwiches were then characterized by surface-enhanced Raman
      scattering (SERS) spectroscopy. The resulting spectra were compared to the bulk
      spectrum of the dimer and to the Ag nanosurface/OPE SERS spectra. The intensities
      of the SERS spectra in both systems exhibit a strong dependence on Ag deposition
      time and the results are also suggestive of intense interparticle coupling of the
      electromagnetic fields in both the AgNW/OPE/Ag and the AgNS/OPE/Ag systems. Three
      previously unobserved bands (1219, 1234, 2037 cm(-1)) arose in the SER spectra of
      the sandwiches and their presence is attributed to the strong enhancement of the
      electromagnetic field which is predicted from the COSMOL computational package.
      The 544 cm(-1) disulfide bond which is observed in the spectrum of solid OPE but
      is absent in the AgNS/OPE/Ag and AgNW/OPE/Ag spectra is indicative of
      chemisorption of OPE to the nanoparticles through oxidative dissociation of the
      disulfide bond.

PMID- 21190894
TI  - Molecular structure, vibrational spectroscopic, first order hyperpolarizability
      and HOMO-LUMO studies of 7-amino-8-oxo-3-vinyl-5-thia-1-azabicyclo[4.2.0]oct-2
      ene-2-carboxylic acid.
AB  - The FT-IR and FT-Raman spectra of 7-amino-8-oxo-3-vinyl-5-thia-1
      azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (7AVCA) were recorded in the region
      4000-400 cm(-1) and 3500-10 cm(-1), respectively. Quantum chemical calculations
      of energies, geometrical structure and vibrational wavenumbers were carried out
      by ab initio HF and density functional theoretical methods invoking 6-311G(d,p)
      basis set. The differences between the observed and scaled wavenumber values of
      most of the fundamentals are very small. The electric dipole moment (MU) and the
      first order hyperpolarizability (beta0) values have been computed quantum
      mechanically. The calculated results show that 7AVCA may have microscopic
      nonlinear optical (NLO) behavior with non-zero values. A detailed interpretation
      of the FT-IR and FT-Raman spectra of 7AVCA is reported. The theoretical IR and
      Raman spectra of 7AVCA have also been constructed. The calculated HOMO and LUMO
      energies show that the charge transfer occurs within the molecule.

PMID- 21190895
TI  - Molecular structure, vibrational spectroscopic (FT-IR, FT-Raman), UV and NBO
      analysis of 2-chlorobenzonitrile by density functional method.
AB  - In this work, we will report a combined experimental and theoretical study on
      molecular structure, vibrational spectra, NBO and UV spectral analysis of 2
      chlorobenzonitrile (2-ClBN). The FT-IR solid phase (4000-400 cm(-1)), and FT
      Raman spectra (3500-50 cm(-1)) of 2-ClBN was recorded. The molecular geometry,
      harmonic vibrational frequencies and bonding features of 2-ClBN in the ground
      state have been calculated by using the density functional methods (BLYP, B3LYP)
      with 6-31G(d,p) as basis set. The assignments of the vibrational spectra have
      been carried out with the help of normal co-ordinate analysis (NCA) following the
      Scaled Quantum Mechanical Force Field Methodology (SQMFF). Stability of the
      molecule arising from hyper conjugative interactions, charge delocalization has
      been analyzed using natural bond orbital (NBO) analysis. The results show that
      charge in electron density (ED) in the sigma* and pi* anti bonding orbitals and
      E2 energies confirms the occurrence of ICT (Intra molecular Charge Transfer)
      within the molecule. The UV spectrum was measured in ethanol solution. The energy
      and oscillator strength calculated by Time-Dependent Density Functional Theory
      (TD-DFT) results complements with the experimental findings. The calculated HOMO
      and LUMO energies also confirm that charge transfer occurs within the molecule.
      Finally calculated results were applied to simulated Infrared and Raman spectra
      of the title compound which show good agreement with observed spectra.

PMID- 21190896
TI  - Vibrational, NMR spectral studies of 2-furoic hydrazide by DFT and ab initio HF
      methods.
AB  - The Fourier transform infrared spectra, 1H NMR and 13C NMR spectra of 2-furoic
      hydrazide have been recorded. Optimized geometry, frequency and intensity of the
      vibrational bands of 2-furoic hydrazide were obtained by the density functional
      theory (DFT) and ab initio levels of theory and also 1H NMR, 13C NMR chemical
      shifts were calculated using 6-31G+(d,p) basis sets. The theoretical values were
      compared with experimental values.

PMID- 21190898
TI  - Resolving relationships between Australian trypanosomes using DNA barcoding data.

PMID- 21190897
TI  - Lck and the nature of the T cell receptor trigger.
AB  - Exactly how ligand binding 'triggers' T cell receptor (TCR) phosphorylation is
      unclear. It has been proposed that ligand engagement by the TCR somehow activates
      the Src kinase Lck, which in turn phosphorylates the receptor. Recent data,
      however, suggest instead that a significant fraction of the Lck in resting T
      cells is already activated and that the proportion of active Lck does not change
      during the early stages of T cell activation. We argue that, caveats
      notwithstanding, these new observations offer support for the 'kinetic
      segregation' model of TCR triggering, which involves spatial reorganization of
      signalling proteins upon ligand binding and requires a fraction of Lck to be
      active in resting T cells.

PMID- 21190899
TI  - Strategy for anti-aquaporin-4 auto-antibody identification and quantification
      using a new cell-based assay.
AB  - NMO-IgG is a specific biomarker of neuromyelitis optica (NMO) that targets the
      aquaporin-4 (AQP4) water channel protein. The current gold standard for NMO-IgG
      identification is indirect immunofluorescence (IIF). Our aim in this study was to
      develop a new quantitative cell-based assay (CBA) and to propose a rational
      strategy for anti-AQP4 Ab identification and quantification. We observed an
      excellent correlation between the CBA and IIF for NMO-IgG/anti-AQP4 detection.
      The CBA appeared more sensitive than IIF but on the other hand, IIF allows the
      simultaneous detection of various auto-Abs, underlining the complementarity
      between both methods. In conclusion, we propose to use IIF for the screening of
      patients at diagnosis in order to identify auto-Abs targeting the central nervous
      system. A highly sensitive, AQP4 specific and quantitative assay such as our CBA
      could be used thereafter to specifically identify the target of the Ab and to
      monitor its serum concentration under treatment.

PMID- 21190900
TI  - Intracarotid amobarbital procedure for epilepsy surgery.
AB  - The intracarotid amobarbital procedure (IAP) has been used for more than half a
      century to determine language dominance and to assess risk for amnesia after
      anterior temporal lobectomy. However, because of the risk associated with
      angiography and the development of noninvasive techniques, the need for the IAP
      when evaluating patients for epilepsy surgery can now be questioned. The purpose
      of this review is to examine the clinical indications and efficacy of the Wada
      test in the preoperative evaluation of epilepsy surgery candidates. This article
      summarizes a debate that took place during the 2009 American Epilepsy Society
      (AES) annual course.

PMID- 21190901
TI  - Rhythmic delta activity represents a form of nonconvulsive status epilepticus in
      anti-NMDA receptor antibody encephalitis.
AB  - Anti-NMDA receptor antibody encephalitis is a limbic encephalitis with
      psychiatric manifestations, abnormal movements, coma, and seizures. The coma and
      abnormal movements are not typically attributed to seizure activity, and slow
      activity is the most common EEG finding. We report drug-resistant nonconvulsive
      status epilepticus as the basis for coma in a 19-year-old woman with anti-NMDA
      receptor antibodies and a mediastinal teratoma. The EEG showed generalized
      rhythmic delta activity, with evolution in morphology, frequency, and field
      typical of nonconvulsive status epilepticus. The status was refractory to
      antiepileptic drugs, repeated drug-induced coma, resection of the tumor,
      intravenous steroids, rituximab, and plasmapheresis. She awoke after the addition
      of felbamate, and the rhythmic delta activity ceased. The rhythmic delta activity
      described with coma in anti-NMDA receptor antibody encephalitis may represent a
      pattern of status epilepticus in some patients. Felbamate, which has NMDA
      receptor antagonist activity, should be studied as a therapeutic agent in this
      condition.

PMID- 21190902
TI  - The correlation between annular treatment margins and biochemical failure in
      prostate brachytherapy patients with optimized intraprostatic dosimetry.
AB  - PURPOSE: To determine whether periprostatic treatment margins correlate with
      biochemical control in prostate brachytherapy patients with optimized
      intraprostatic dosimetry. METHODS AND MATERIALS: Nineteen biochemically failed
      brachytherapy patients were matched to 74 dosimetric and clinically equivalent
      nonfailures. The median followup time for the entire study population was 9.4
      years. Eligibility requirements included a Day 0 intraprostatic D(90) of 100% or
      greater and V(100) of 90% or greater, absence of androgen deprivation therapy,
      and no evidence of distant metastasis in biochemically failed patients. A 5-mm
      annulus was constructed around the perimeter of each prostate. D(90) and V(100)
      at the anterior, posterior, superior, inferior, right lateral, and left lateral
      aspects of the annulus were evaluated for patients with biochemically controlled
      and failed disease. Biochemical progression-free survival (bPFS) was defined as a
      prostate-specific antigen level of 0.40ng/mL or less after nadir. D(90) and
      V(100) parameters were compared between the controlled and failed groups using
      logistic regression. Predictors of biochemical failure were identified using Cox
      regression. RESULTS: No statistically significant differences in prostate
      specific antigen level, Gleason score, percent positive biopsies, or
      intraprostatic dosimetry were observed between the controlled and failed
      patients. The D(90) and V(100) at the anterior, posterior, superior, inferior,
      right lateral, and left lateral aspects of the annulus were not statistically
      different between biochemically controlled and failed groups. CONCLUSION: In this
      study, there was no relationship observed between annular dosimetry and
      biochemical control. It is unlikely that further radial dose intensification
      would have altered treatment outcome in this population of patients with
      optimized intraprostatic dosimetry.

PMID- 21190903
TI  - Use of cone-beam imaging to correct for catheter displacement in high dose-rate
      prostate brachytherapy.
AB  - PURPOSE: To determine the magnitude of catheter displacement between time of
      planning and time of treatment delivery for patients undergoing high dose-rate
      (HDR) brachytherapy, the dosimetric impact of catheter displacement, and the
      ability to improve dosimetry by catheter readjustment. METHODS AND MATERIALS:
      Twenty consecutive patients receiving single fraction HDR brachytherapy underwent
      kilovoltage cone-beam CT in the treatment room before treatment. If catheter
      displacement was apparent, catheters were adjusted and imaging repeated. Both
      sets of kilovoltage cone-beam CT image sets were coregistered off-line with the
      CT data set used for planning with rigid fusion of anatomy based on implanted
      fiducials. Catheter displacement was measured on both sets of images and
      dosimetry calculated. RESULTS: Mean internal displacement of catheters was 11mm.
      This would have resulted in a decrease in mean volume receiving 100% of
      prescription dose (V(100)) from the planned 97.6% to 77.3% (p<0.001), a decrease
      of the mean dose to 90% of the prostate (D(90)) from 110.5% to 72.9% (p<0.001),
      and increase in dose to 10% of urethra (urethra D(10)) from 118% to 125%
      (p=0.0094). Each 1cm of catheter displacement resulted in a 20% decrease in
      V(100) and 36% decrease in D(90). Catheter readjustment resulted in a final
      treated mean V(100) of 90.2% and D(90) of 97.4%, both less than planned. Mean
      urethra D(10) remained higher at126% (p=0.0324). CONCLUSIONS: Significantly,
      internal displacement of HDR catheters commonly occurs between time of CT
      planning and treatment delivery, even when only a single fraction is used. The
      adverse effects on dosimetry can be partly corrected by readjustment of catheter
      position.

PMID- 21190904
TI  - Abrupt telomere losses and reduced end-resection can explain accelerated
      senescence of Smc5/6 mutants lacking telomerase.
AB  - The highly conserved Structural Maintenance of Chromosome (SMC) proteins are
      crucial for the formation of three essential complexes involved in high fidelity
      chromosome transmission during cell division. Recently, the Smc5/6 complex has
      been reported to be important for telomere maintenance in yeast and also in
      cancerous human ALT cells, where it could function in a homologous recombination
      based (HR) telomere maintenance pathway. Here, we investigate the possible roles
      of the budding yeast Smc5/6 complex in maintaining appropriate chromosome end
      structures allowing cell survival in absence of telomerase. The results show that
      cells harbouring mutant alleles of genes encoding Smc5/6-complex proteins rapidly
      stop growing after telomerase loss. Furthermore, this telomerase-induced growth
      arrest is much more pronounced as compared to cultures with a functional Smc5/6
      complex. Bulk telomere sequence loss is not increased in the mutant cells and the
      evidence suggests that Smc5/6 slows senescence through a partially HR-independent
      pathway. We propose that in yeast, the Smc5/6-complex is required for efficient
      and timely termination of DNA replication and repair at telomeres to avoid
      stochastic telomere loss during cell division. Consistent with this hypothesis,
      sequencing of telomeres from telomerase-positive smc5/6 mutant cells revealed a
      higher frequency of telomere breakage events. Finally, the results also show that
      on dysfunctional telomeres, the generation of 3'-single stranded DNA is impaired,
      suggesting that the complex may also participate in the formation of single
      stranded overhangs which are thought to be the substrates for telomere repeat
      replenishment in the absence of telomerase.

PMID- 21190905
TI  - Highly sensitive and selective derivatization-LC method for biomolecules based on
      fluorescence interactions and fluorous separations.
AB  - A fluorescence derivatization LC method is a powerful tool for the analysis with
      high sensitivity and selectivity of biological compounds. In this review, we
      introduce new types of fluorescence derivatization LC analysis methods. These are
      (1) detection-selective derivatization methods based on fluorescence interactions
      generated from fluorescently labeled analytes: excimer fluorescence
      derivatization and fluorescence resonance energy transfer (FRET) derivatization;
      (2) separation-selective derivatization methods using the fluorous separation
      technique: fluorous derivatization, F-trap fluorescence derivatization, and
      fluorous scavenging derivatization (FSD).

PMID- 21190906
TI  - Development of an LC-MS/MS method for the quantitation of 55 compounds prescribed
      in combined cardiovascular therapy.
AB  - This paper reports an LC-MS/MS method with positive electrospray ionization for
      the screening of commonly prescribed cardiovascular drugs in human plasma,
      including compounds with antihypertensive (57), antidiabetic (12), hypolipemiant
      (5), anticoagulant (2) and platelet anti-aggregation (2) effects. Sample
      treatment consisted of a simple protein precipitation with MeOH/0.1 M ZnSO4 (4:1,
      v/v) solution after the addition of internal standard, followed by evaporation
      and reconstitution. Analytes separation was performed on a Polar-RP column (150 m
      x 2 mm, 4 MUm) using a gradient elution of 15 min. The MS system was operated in
      MRM mode, monitoring one quantitation and one confirmation transition for each
      analyte. The recovery of the protein precipitation step ranged from 50 to 70% for
      most of the compounds, while some were considerably affected by matrix effects.
      Since several analytes fulfilled the linearity, accuracy and precision values
      required by the ICH guidelines, the method proved to be suitable for their
      quantitative analysis. The limits of quantitation varied from 0.38 to 9.1 MUg/L
      and the limits of detection from 0.12 to 5.34 MUg/L. The method showed to be
      suitable for the detection of plasma samples of patients under cardiovascular
      treatment with the studied drugs, and for 55 compounds reliable quantitative
      results could be obtained.

PMID- 21190907
TI  - [Prognostic evaluation of arterial switch in the transposition of great
      arteries].
AB  - INTRODUCTION AND OBJECTIVES: The arterial switch is the procedure of choice for
      transposition of great arteries, with or without ventricular septal defect. The
      aim of this study was to identify risk factors for hospital mortality. METHODS:
      The study included 121 children between January 1994 and June 2008. Of these, 80
      (66%) were diagnosed with intact ventricular septum, and 41 (34%) with
      ventricular septal defect. Variables were collected pre-operatively, during
      surgery, and postoperatively. RESULTS: The mean age was 11 [8 to 16] days and a
      mean weight of 3.5 [3.0 to 3.7] kg. A ventricular septal defect was closed in 11
      children (9.1%). A total of 81.8% had a normal coronary pattern. There was
      delayed closure of the chest in 38 patients (31.4%). The hospital mortality was
      11.6%, decreasing over the past 5 years to 2.1%. The weight, abnormal coronary
      pattern, time of cardiopulmonary bypass, mean arterial pressure at admission,
      pulmonary dead space, and delayed closure of the chest, were risk factors of
      mortality. The model that best predicts death, consists of the mean arterial
      pressure at admission, and delayed closure of the chest. CONCLUSIONS: The
      reduction in extracorporeal circulation time and the use of delayed closure of
      the chest, have helped to reduce mortality. The abnormal coronary pattern remains
      a risk factor for mortality. In children with delayed closure of the chest, a
      mean arterial pressure at admission >= 47.5 mmHg is a goal to achieve.

PMID- 21190909
TI  - Paraneoplastic pemphigus associated with non-Hodgkin's lymphoma.

PMID- 21190910
TI  - A study on effects of glutathione s-transferase from silkworm on CCL4-induced
      mouse liver injury.
AB  - To assess the hepatoprotective activity of Glutathione S-transferase(GSTsw),
      extracted and purified from silkworm, in experimental acute mice liver injury and
      explore mechanisms. Mice were divided into five groups: control group, carbon
      tetrachloride (CCl4) group, and three treatment groups that received CCl4 and
      GSTsw at doses of 0.083 mg*g(-1), 0.0415 mg*g(-1) and 0.0207 mg*g(-1) for 3 days.
      ALT in serum, GST, SOD and T-AOC in liver tissue homogenate, and changes in liver
      pathology in the five groups were studied. CCl4 administration led to
      pathological and biochemical evidence of liver injury as compared to untreated
      controls. GSTsw administration led to significant protection against CCl4-induced
      changes in liver pathology. It was also associatedwith significantly lower serum
      ALT levels, higher GST-SOD and T-AOC level in live tissue homogenate. Thus, GSTsw
      showed protective activity against CCl4-induced hepatotoxicity in mice.

PMID- 21190911
TI  - Reversal of haloperidol-induced motor deficits by mianserin and mesulergine in
      rats.
AB  - Although haloperidol is widely prescribed for the treatment of schizophrenia, its
      beneficial effects are accompanied by extrapyramidal side effects (EPS). Role of
      5-HT-2A/2C receptors in the attenuation of acute Parkinsonian-like effects of
      typical antipsychotics is investigated by prior administration of mianserin and
      mesulergine to rats injected with haloperidol. In the first part of study effects
      of various doses of haloperidol (0.5, 1.0, 2.5 and 5.0 mg/kg) were determined on
      motor activity and a selected dose (1 mg/kg) was used to monitor attenuation of
      parkinsonian effects by two different doses of 5-HT-2A/2C receptor antagonists
      mianserin (2.5 & 5.0 mg/kg) and mesulergine (1.0 & 3.0 mg/kg). Rats treated with
      haloperidol at doses of 0.5-5.0 mg/kg exhibited impaired motor coordination and a
      decrease in exploratory activity in an open field. The dose response curve showed
      that at a dose of 1 mg/kg significant and submaximal effects are produced on
      motor coordination and exploratory activity. Coadministration of mianserin and
      mesulergine attenuated and reversed haloperidol-induced motor deficits in a dose
      dependent manner. The mechanism involved in the attenuation / reversal of
      haloperidol-induced parkinsonian like symptoms by mianserin and mesulergine is
      discussed. Prior administration of mianserin or mesulergine may be of use in the
      alleviation of EPS induced by conventional antipsychotic drugs.The findings have
      potential implication in the treatment of schizophrenia and motor disorders.

PMID- 21190912
TI  - Effect of aluminium metal on glutathione (GSH) level in plasma and cytosolic
      fraction of human blood.
AB  - Aluminium is being used in the medicines in the form of antacids. The Aluminium
      metal can be leached from our utensils and can harm the body for its side
      effects, if become available to the systemic circulation. So it is important to
      check the effect of Aluminum on the Glutathione in vivo condition. Ellman method
      was used to determine the effect of Aluminum on GSH level in whole blood
      spectrophotometerically. 5,5-Dithiobis, 2-Nitrobenzoic Acid, Glutathione,
      Aluminium sulphate, phosphate buffer, HCl (Hydrochloric acid) and other
      laboratory instruments were used to conduct the research work. Time dependent
      effect of Aluminum on Glutathione level in whole blood was also checked and
      decrease was observed. This study also shows the effect of Aluminum as helping
      agent for the Glutathione to enhance the antioxidant system of the body or a
      cause for depletion of reduced Glutathione.

PMID- 21190913
TI  - Spectrophotometric and spectrofluorimetric methods for determination of
      Racecadotril.
AB  - Two accurate and sensitive spectrophotometric and spectrofluorimetric methods
      were developed for determination of Racecadotril. In the first method reduction
      of Fe3+ into Fe2+ in presence of o-phenanthroline by Racecadotril to form a
      stable orange-red ferroin chelate [Fe-(Phen)3]2+ was the basis for its
      determination. The absorbance at 510 nm was measured and linear correlation was
      obtained in the concentration range of 2.5-25 ug mL(-1). In the second method the
      native fluorescence of Racecadotril in acetonitrile solvent at lambda=319 nm when
      excitation was at 252 nm is used for its determination. Linear correlation was
      obtained in the concentration range of 50 to 500 ng mL(-1). The proposed methods
      were applied for determination of Racecadotril in bulk powder with mean accuracy
      of 100.39+/-1.239 for the spectrophotometric method and 100.09+/-1.042 for the
      spectrofluorimetric method. The proposed methods were successfully applied for
      determination of Racecadotril in its pharmaceutical dosage form.

PMID- 21190914
TI  - Antimicrobial activity of erythromycin and clarithromycin against clinical
      isolates of Escherichia coli, Staphylococcus aureus, Klebsiella and Proteus by
      disc diffusion method.
AB  - Fifty clinical isolates comprising of Escherichia coli, Staphylococcus aureus,
      Klebsiella and Proteus were collected from different local pathological
      laboratories and their resistant pattern against two well known macrolides;
      erythromycin and clarithromycin were studied using disc diffusion method.
      Klebsiella (41.67% against erythromycin and 58.34% against clarithromycin) and
      Proteus (66.67% against erythromycin and clarithromycin) species were found to be
      more resistant against the studied macrolides as compared to the rest of
      organisms. In case of Staphylococcus aureus and Escherichia.coli, resistant found
      were 27.78% and 23.54% against erythromycin and 22.23% and 35.30% against
      clarithromycin respectively. It is concluded from these figures that microbial
      resistance against these macrolides are increasing in our population which is
      alarming and therefore it is recommended to physicians to prescribe these
      antibiotics unless no other substitute is available in clinical practices.

PMID- 21190915
TI  - Kinetics and mechanism of reduction of Fe (III) salicylate complex by
      hydroquinone.
AB  - The violet color complex FeSal+ was prepared by reaction of Salicylic acid and
      Ferric Chloride in acidic medium up to pH 3.5 in formate buffer at ionic strength
      0.1 M. Reduction kinetics of FeSal+ complex at pseudo first order condition have
      been studied spectrophotometrically by a reductant i.e. Hydroquinone. Reduction
      behaviour shows that reduction is much fast and pH dependent. A mechanism to
      account for observation is also proposed along with the rate law.

PMID- 21190916
TI  - Antioxidant and antibacterial activities of selected varieties of thai mango seed
      extract.
AB  - This study reports the antioxidant and antibacterial activities of four fresh
      mango seed extracts from Thai varieties. Total phenol contents determined by the
      Folin-ciocalteu method revealed the highest values to be in MKE, Chok-a-nan
      variety (399.8 mgGAE/g extract) and MSE of Nam-dok-mai variety (377.2 mgGAE/g
      extract). Both extracts showed potent ABTS+ radical and DPPH radical scavenging
      activities with the lower half inhibition concentration (IC50) values than those
      of the reference compounds; vitamin C, trolox and BHA, respectively. Their
      antioxidant property of MSE and MKE is strongly correlated with the total phenol
      contents (r=0.98 and 0.98, respectively). When combined the MSE and MKE of the
      Fah-lun variety showed the strongest antioxidant activity. All mango seed
      extracts showed interesting antibacterial activity against both gram positive and
      gram negative bacteria as determined by disc diffusion method. The most sensitive
      pathogenic strain inhibited by all extracts (especially Kaew variety) was
      Pseudomonas aeruginosa ATCC 27853. This work suggests potential applications for
      practical uses of mango seed extracts from Thai varieties, as sources of
      antioxidant and antibacterial agents.

PMID- 21190917
TI  - Bioequivalence study of two oral formulations of clarithromycin in human male
      subjects.
AB  - To assess the bioequivalence of tablets formulations of Clarithromycin 500 mg
      each of test and reference products. A single post oral dose of each formulation
      was given to 14 male healthy volunteers. The study was conducted phase 1, open
      label, randomized, complete two-way crossover designed with 7 days wash out
      period. The plasma concentration of Clarithromycin was quantified by validated
      microbiological assay method. The precision of the method was evaluated using
      calibrated 14-hydroxyClarithromycin concentration was detected semi
      quantitatively as equivalent of Clarithromycin/ml. The peak plasma concentrations
      of (3.63+/-0.80 ug/ml) and (3.31+/-0.35 ug/ml) was attained in about 1.42 hours
      and 1.49 hours for both test and reference Clarithromycin tablets respectively.
      The mean+/-SD values for total area under the curve (AUC) were 22.07+/-4.90 and
      20.16+/-2.35 h.mg/L for both test and reference tablets respectively. This study
      indicated that the differences in all the bioequivalence parameters for test and
      reference Clarithromycin formulations are statistically non-significant; hence
      both formulations are considered bioequivalent.

PMID- 21190918
TI  - Cummulative toxicities on lipid profile and glucose following administration of
      anti-epileptic, anti-hypertensive, anti-diabetic and anti-arrhythmic drugs.
AB  - Reporting of undesirable drug reactions is a problem in all countries, even those
      with sophisticated drug regulatory bodies. However we can expect a horrible
      picture in developing countries like Pakistan where drug regulatory control is
      very poor, hence present study has been exclusively designed to explore the
      outcome of individual administration of antiepileptic, antihypertensive,
      antidiabetic, antiarrhythmic drugs and their combinations on lipid profile and
      glucose. The study was conducted on healthy rabbits of either sex. Biochemical
      tests were performed at the completion of dosing i.e. on 61st day and again after
      drug-free interval of 15 days. Present study provides detailed evaluation of
      adverse effects on lipid profile and glucose, results of the study suggests that
      animals received amiodarone-glibenclamide-verapamil-oxcarbazepine combination did
      not revealed any significant changes but animals received amiodarone
      glibenclamide-losartan potassium-oxcarbazepine and amiodarone-glibenclamide
      captopril-oxcarbazepine combinations revealed significant changes. However more
      studies on large number of animals and human beings are required to justify the
      use of multiple drug administration, since trial in man is the only way of
      establishing drug interactions.

PMID- 21190919
TI  - Antinociceptive and anti-hyperglycemic activity of methanol leaf extract of
      Cyperus scariosus.
AB  - The objective of the present study was to investigate the antinociceptive and
      anti-hyperglycemic activity of methanolic leaf extract of Cyperus scariosus.
      Antinociceptive activity was determined using a model of acetic acid-induced
      gastric pain in mice and anti-hyperglycemic activity through glucose tolerance
      test using glucose loaded mice. In writhing assays induced by acetic acid, the
      methanolic leaf extract showed dose dependent significant pain inhibition
      compared to control. The maximum writhing inhibition (46.62%) was found at a dose
      of 200 mg/kg body weight which was less than that of the positive control,
      aspirin (56.74%), when used at the same dose. Anti-hyperglycemic activity of the
      extract was also found to be significant in mice loaded with glucose at doses of
      200 and 400 mg/kg body weight. Maximum tolerance (42.86%) was showed at 400 mg
      extract/kg body weight, which compared favorably with that of glibenclamide at 10
      mg/kg body weight (57.62%). In summary, the methanol extract of C. scariosus
      leaves has had beneficial effects as a pain reliever and also in reducing the
      elevated blood glucose level of hyperglycemic mice.

PMID- 21190920
TI  - In vivo antimalarial activities of ethanolic crude extracts and fractions of leaf
      and root of Carpolobia lutea.
AB  - Carpolobia lutea (leaves and root) is used traditionally as malarial remedy by
      the Ibibios of Niger Delta of Nigeria and Benin. This study was aimed to
      investigate the antiplasmodial potentials of the crude leaf and root extracts of
      this plant as well as their fractions in vivo in Plasmodium berghei berghei
      infected mice to give scientific proof to the ethnobotanical claims and correlate
      with the reported in vivo activity. The ethanolic extracts of Carpolobia lutea
      leaf (245-735 mg/kg/day) and root (7-21 mg/kg/day) were screened for blood
      plasmocidal activity against chloroquine-sensitive Plasmodium berghei in mice.
      The antimalarial activity in 4-day and curative tests was evaluated. Carpolobia
      lutea leaf extract (245-735 mg/kg/day) and fractions exhibited significant
      (p<0.05-0.01) antiplasmodial activity both in 4-day early infection test and in
      established infection with a considerable mean survival time which was
      incomparable to that the standard drug, chloroquine (5 mg/kg/day). The root
      extract (7-21 mg/kg/day) and fractions also demonstrated a promising blood
      schizontocidal activity in early and established infections. These plant extracts
      and fractions possess considerable antiplasmodial activities which justify their
      use in ethnomedicine and can be exploited in the control of malaria.

PMID- 21190921
TI  - Therapeutic effects of ciprofloxacin on the pharmacokinetics of carbamazepine in
      healthy adult male volunteers.
AB  - Carbamazepine is a (CYP1A2 and CYP3A4 enzyme inducer) medicine which is used by
      epileptic patients for a long time. During the course of therapy, patients are
      generally caught by other diseases like urinary tract infections, upper
      respiratory tract infection, skin and soft tissue infection etc. To cure them,
      physicians commonly prescribe fluoroquinolones like Ciprofloxacin (CYP1A2
      inhibitor) along with Carbamazepine (CBZ). Interactions may result without
      recognition which may lead to unforeseen toxicity, untoward effects or even
      therapeutic failure. Therefore, studies were conducted to investigate the effect
      of Ciprofloxacin on the pharmacokinetics of carbamazepine in healthy adult male
      volunteers. The main objective of this study was to generate new knowledge
      regarding CBZ and ciprofloxacin interaction for physicians and research workers
      dealing with these medicines. Eight healthy adult male volunteers were selected
      to assess the effect of ciprofloxacin on the pharmacokinetics of carbamazepine.
      After overnight fast the selected male volunteers were given CBZ orally. Blood
      samples were drawn at different time intervals after medication. Then the same
      volunteers were given CBZ along with ciprofloxacin. Blood samples were again
      drawn at the same time intervals as done previously. Plasma was separated from
      the blood samples. Concentration of CBZ in the plasma samples was determined by
      using HPLC technique. Results of the present study indicated that ciprofloxacin
      significantly increased the plasma concentration of CBZ when given concurrently
      to the healthy adult male volunteers. Ciprofloxacin increased Cmax, AUC and t1/2
      while it decreased the CL and Vd of CBZ when administered concurrently to the
      adult volunteers. Change in pharmacokinetic parameters was due to slow metabolism
      or elimination of CBZ when given concurrently with ciprofloxacin to the adult
      volunteers. This is probably due to the inhibition of CYP3A4 isoenzyme by
      ciprofloxacin which is responsible for metabolism of CBZ. Ciprofloxacin increased
      the plasma concentration of CBZ so dose adjustment as well as drug monitoring of
      CBZ is required when both the drugs are given concurrently. The knowledge
      regarding interaction between ciprofloxacin and CBZ would be helpful for the
      pharmaceutical industries, physicians and a blessing for the patients.

PMID- 21190922
TI  - Pharmacokinetics and dosage regimen of ciprofloxacin following single
      intramuscular administration in Teddy goats.
AB  - The objective of this study was to determine the pharmacokinetics and dosage
      regimen of ciprofloxacin in Teddy goats. Ciprofloxacin was administered
      intramuscularly at 5 mg/kg body weight in each of eight animals. Following drug
      administration, blood samples were collected at different time intervals and
      analyzed for ciprofloxacin using HPLC. Pharmacokinetic parameters were calculated
      using two compartment open model. Peak plasma concentration (Cmax) of
      ciprofloxacin, 1.77+/-0.20 ug/ml was achieved at 0.90+/-0.04 hours (Tmax). Values
      for half-life of absorption (t1/2 abs), distribution (t1/2 alpha) and elimination
      (t1/2 beta) were 0.52+/-0.04, 0.52+/-0.04 and 2.62+/-0.39 hours, respectively.
      The value for apparent volume of distribution (Vd) was 3.76+/-0.92 l/kg, area
      under-the-curve (AUC) 5.89+/-0.91 ug.hr/ml and total body clearance (CL) was
      1.09+/-0.11 l/hr/kg. Based on these results, it was concluded that calculated
      dose should be higher than the dose recommended by the manufacturer to treat
      susceptible bacteria in goats.

PMID- 21190923
TI  - Molecular analysis of guanidinoacetate-n-methyltransferase (GAMT) and creatine
      transporter (SLC6A8) gene by using denaturing high pressure liquid chromatography
      (DHPLC) as a possible source of human male infertility.
AB  - The creatine/phosphocreatine system is essential for cellular phosphate coupled
      energy storage and production, particularly in tissues subject to high metabolic
      demands. Male factor infertility is a common condition with unknown etiology in
      most of the cases. Sperm abnormalities could possibly lead to infertility. As
      sperm motility depends on intact mitochondrial function and energy levels. Thus
      reduced intracellular creatine stores may contribute to decreased sperm motility
      leading to male infertility as creatine /phosphocreatine system plays major role
      in making and breaking of ATP, thus in energy kinetics. We developed and
      validated a denaturing high performance liquid chromatograph (DHPLC) method for
      the molecular analysis of SLC6A8 and GAMT genes involve in creatine biosynthesis
      and transport as a possible source of human male infertility by analyzing DNA
      from 64, clinically confirmed, infertile men. No mutation/polymorphism was
      detected in the exonic regions of both genes in all the patients and in fertile
      healthy controls indicating that SLC6A8 and GAMT genes may not be directly
      involved in human male infertility.

PMID- 21190924
TI  - Anti-mycobacterial activity of garlic (Allium sativum) against multi-drug
      resistant and non-multi-drug resistant mycobacterium tuberculosis.
AB  - Emergence of multi-drug resistant (MDR) and extensively drug resistant (XDR) TB
      throughout the developing world is very disturbing in the present scenario of TB
      management. There is a fundamental need to explore alternative anti-TB agents.
      Hence natural plants should be investigated to understand their antimicrobial
      properties and safety. Garlic (Allium sativum) is one of natural plant which
      possesses variety of biological properties like anti-tumor, anti-hyperlipedemic
      and anti-microbial etc. The present study was evaluated for anti-bacterial
      activity of garlic against non-MDR and MDR isolates of M. tuberculosis. A total
      of 20 clinical isolates of MTB including 15 MDR and 5 non-MDR were investigated.
      Ethanolic extract of garlic was prepared by maceration method. Minimum inhibitory
      concentration (MIC) was performed by using 7H9 middle brook broth dilution
      technique. MIC of garlic extract was ranged from 1 to 3 mg/ml; showing inhibitory
      effects of garlic against both non-MDR and MDR M. tuberculosis isolates.
      Alternate medicine practices with plant extracts including garlic should be
      considered to decrease the burden of drug resistance and cost in the management
      of diseases. The use of garlic against MDR-TB may be of great importance
      regarding public health.

PMID- 21190925
TI  - Enhanced local anesthetic action of mepivacaine from the bioadhesive gels.
AB  - Mepivacaine, an amide-type local anesthetic, has been used to relieve local pain.
      Among the many drug delivery systems, transdermal drug delivery has some
      advantages, as it provides controlled drug delivery for an extended period of
      time. To develop new gel formulations that have suitable bioadhesion, the
      bioadhesive force of hydroxypropyl methylcellulose (HPMC) was assessed using an
      auto-peeling tester. The effect of drug concentration on drug release from 2%
      HPMC gel was studied using synthetic cellulose membrane at 37+/-0.5 degrees C.
      The drug concentrations tested were 0.5, 1, 1.5, 2, and 2.5%. The effect of
      temperature on drug release from the 2% drug gel was evaluated at 27, 32, 37 and
      42 degrees C. To increase the skin permeation of mepivacaine from HPMC gel,
      enhancers such as saturated and unsaturated fatty acids, pyrrolidones, propylene
      glycol derivatives, glycerides, and non-ionic surfactants were incorporated into
      the mepivacaine-HPMC gels. The enhancing effect of the enhancer on drug
      permeation was then examined in the modified Keshary-Chien cell. For the efficacy
      study, the anesthetic action of the formulated mepivacaine gel containing
      enhancer and vasoconstrictor was evaluated with the tail-flick analgesimeter.
      Among the various kinds of HPMC, HPMC-K100M gel showed the highest viscosity and
      bioadhesive force. As the viscosity of the HPMC gels increased, the bioadhesive
      forces increased. Increasing the drug concentration or temperature increased the
      drug release rate. Among the enhancers used, polyoxyethylene 2-oleyl ether showed
      the greatest enhancement of permeation. Based on the area under the efficacy
      curve of the rat tail flick test curve, mepivacaine gel containing
      polyoxyethylene 2-oleyl ether and tetrahydrozoline showed prolonged and increased
      local anesthetic action compared to the control. For bioadhesive mepivacaine gels
      with enhanced local anesthetic action, mepivacaine gels containing penetration
      enhancer and vasoconstrictor could be developed with the bioadhesive polymer,
      HPMC.

PMID- 21190926
TI  - Suicide terrorism as a socially approved form of suicide.

PMID- 21190927
TI  - No-suicide contracts, no-suicide agreements, and no-suicide assurances: a study
      of their nature, utilization, perceived effectiveness, and potential to cause
      harm.
AB  - BACKGROUND: Suicide prevention contracting (SPC) procedures are often afforded
      clinical practice validity in the absence of evidence attesting to their efficacy
      and validity. AIMS: This study sought to develop a contemporary profile of SPC,
      identifying factors associated with utilization, perceived effectiveness, and to
      describe potentially detrimental factors when activating SPC. METHODS: A
      questionnaire was mailed to a sample of mental health practitioners comprising
      physicians, mental health nurse practitioners, and allied health practitioners to
      inquire about their practices and experiences with SPC. RESULTS: There were 420
      valid responses, a response rate of 31%. Participants confirmed three types of
      SPC procedures in operation: (1) 355 (85%) having used verbal no-suicide
      assurances (NSAs); (2) 317 (76%) using verbal no-suicide agreements (NSAg); and,
      (3) 154 (37%) using written no-suicide contracts (NSC). The profiled procedures
      and their clinical application indicate that participants perceived differences
      in the diagnostic, therapeutic, and medico-legal utility of all three SPC
      procedures. Importantly, SPC procedures were shown to have a multifaceted
      potential for detrimental outcomes for patients and practitioners. CONCLUSIONS:
      Until now, SPC had represented a poorly understood and remains a questionable
      clinical practice intervention. Education initiatives are required that alert
      mental health practitioners to the dangers of SPC for patients and practitioners
      alike, and to present alternative interventions containing less risk.

PMID- 21190928
TI  - Reassessment of suicide attempters at home, shortly after discharge from
      hospital.
AB  - BACKGROUND: Assessment of suicide attempters in a general hospital may be
      influenced by the condition of the patient and the unfavorable circumstances of
      the hospital environment. AIMS: To determine whether the results of a
      reassessment at home shortly after discharge from hospital differ from the
      initial assessment in the hospital. METHODS: In this prospective study,
      systematic assessment of 52 suicide attempters in a general hospital was compared
      with reassessment at home, shortly after discharge. RESULTS: Reassessments at
      home concerning suicide intent, motives for suicide attempt, and dimensions of
      psychopathology did not differ significantly from the initial hospital
      assessment. However, patients' motives for the suicide attempt had changed to
      being less impulsive and more suicidal, worrying was significantly higher, and
      self-esteem was significantly lower. A third of the patients had forgotten their
      aftercare arrangements and most patients who initially felt no need for
      additional help had changed their mind at reassessment. CONCLUSIONS: Results from
      this group of suicide attempters suggest that a brief reassessment at home
      shortly after discharge from hospital should be considered.

PMID- 21190929
TI  - The suicidal process and self-esteem.
AB  - BACKGROUND: It has not been made clear whether self-esteem is associated with the
      severity of suicidal behavior. AIMS: To test the association between responses to
      a self-esteem inventory and levels of suicidal behavior as conceptualized in the
      notion of the suicide process. METHODS: Questions on the severity of suicidal
      behavior over the lifespan (death wishes, ideation, plans, and attempts), as well
      as a self-esteem inventory, were administered to 227 university undergraduates.
      RESULTS: A negative relationship was found between the level of suicidality and
      self-esteem. As hypothesized, there were fewer cases in each succeeding level of
      seriousness of suicidal behavior. However, nearly all cases from any particular
      level were contained in the cohort of individuals who had displayed suicidal
      behavior at a less serious level. CONCLUSIONS: This suggests a possible
      progression through each of the stages of suicidal behavior, with very few cases
      showing a level of suicidal behavior that was not associated with a previous,
      less serious, form. It was hypothesized that early entry into the suicidal
      process may be indicated by low self-esteem, thus, allowing for a more timely
      preventive intervention.

PMID- 21190930
TI  - Suicidal ideation and suicide attempt among adolescents in Western Jamaica: a
      preliminary study.
AB  - BACKGROUND: Although extensive studies on adolescent suicidal behavior have been
      conducted in developed countries such as the United States, little data exist on
      risk factors for suicide among adolescents in culturally and socially
      disadvantages settings, such as Jamaica. AIMS: To conduct a preliminary
      investigation of risk factors associated with suicide ideation and attempt among
      youths in Western Jamaica. METHODS: We conducted a cross-sectional study of 342
      adolescents aged 10-19 years from 19 schools. RESULTS: Multivariate analysis
      showed that a history of self-violence, violent thoughts toward others, mental
      health diagnoses other than depression, and a history of sexual abuse were
      positively associated with suicide attempt. Sexual abuse, mental health diagnoses
      other than depression, self-violence, and ease of access to lethal
      substances/weapons were positively associated with suicide ideation. CONCLUSIONS:
      We found a relatively high prevalence of suicide ideation and suicide attempts
      among adolescents living in Western Jamaica. An accurate understanding of the
      prevailing risk factors for suicide attempts will promote a more sympathetic
      approach to victims and facilitate prevention efforts.

PMID- 21190931
TI  - Suicide by pesticide poisoning: findings from the island of Crete, Greece.
AB  - BACKGROUND: The role of pesticides in suicidal acts has not yet received adequate
      attention in Greece despite an evident rise of 39% in pesticide use over the
      period 1990-1992 to 2002-2004. AIMS: To investigate the epidemiology of pesticide
      suicide on the Greek island of Crete, a largely rural agricultural area, and by
      further exploring the victim profiles, as well as patterns and trends of
      pesticide ingestion, to suggest probable preventive measures. METHODS: Self
      poisoning suicides between 1999 and 2007 were reviewed and information gathered
      was entered into a computerized database. RESULTS: The overall incidence of
      intentional pesticide poisoning was 1.7 per 100,000, representing the second most
      frequently used suicide method after hanging. The victim profile was composed of
      the following features: middle aged male, rural habitant, who carried out a
      suicidal act by consuming primarily methomyl or paraquat (WHO toxicity class Ib
      and class II, respectively). As to the place of death, the vast majority was
      found dead in the place of intoxication. CONCLUSIONS: Pesticide self-poisoning
      accounts for a quarter of the suicides in Crete. More detailed research is
      required to identify aspects of these deaths amenable to prevention, but measures
      such as bans on the most toxic pesticides and changes in storage practice would
      appear to be sensible initial approaches.

PMID- 21190932
TI  - Suicidal ideation and its correlates in prisoners: a comparative study in China.
AB  - BACKGROUND: Suicide is one of the leading causes of prisoners' death, and, as a
      group, inmates have higher suicide rates than their community counterparts.
      However, the prevalence of suicidal ideation among Chinese inmates and their
      risks of suicide remain unknown. AIMS: This study investigates the prevalence of
      suicidal ideation among Chinese incarcerated populations and its risk and
      protective factors. METHODS: We randomly selected three types of prisoners (N =
      690) and a sample of college students (n = 248) from four correction facilities
      and a police academy in China. A self-report questionnaire with standardized
      scales translated from the West was administered to the samples. RESULTS: The
      prevalence of suicidal ideation among Chinese inmates is similar to that found
      among inmates in the West. The correlates of suicidal ideation for the Chinese
      inmates are also in line with what has been found in general populations.
      CONCLUSIONS: It is suggested that Chinese inmates have the same risk factors and
      protective factors for suicidal ideation as the general population in China.
      Suicide prevention in Chinese prisons can learn from and inform suicide
      prevention work for the general population.

PMID- 21190935
TI  - Low-dose valganciclovir for cytomegalovirus prophylaxis in organ transplantation:
      is less really more?

PMID- 21190937
TI  - Evidence that the thyroid-stimulating hormone (TSH) receptor transmembrane domain
      influences kinetics of TSH binding to the receptor ectodomain.
AB  - Thyroid-stimulating hormone (TSH)-induced reduction in ligand binding affinity
      (negative cooperativity) requires TSH receptor (TSHR) homodimerization, the
      latter involving primarily the transmembrane domain (TMD) but with the
      extracellular domain (ECD) also contributing to this association. To test the
      role of the TMD in negative cooperativity, we studied the TSHR ECD tethered to
      the cell surface by a glycosylphosphatidylinositol (GPI) anchor that multimerizes
      despite the absence of the TMD. Using the infinite ligand dilution approach, we
      confirmed that TSH increased the rate of dissociation (k(off)) of prebound (125)I
      TSH from CHO cells expressing the TSH holoreceptor. Such negative cooperativity
      did not occur with TSHR ECD-GPI-expressing cells. However, even in the absence of
      added TSH, (125)I-TSH dissociated much more rapidly from the TSHR ECD-GPI than
      from the TSH holoreceptor. This phenomenon, suggesting a lower TSH affinity for
      the former, was surprising because both the TSHR ECD and TSH holoreceptor contain
      the entire TSH-binding site, and the TSH binding affinities for both receptor
      forms should, theoretically, be identical. In ligand competition studies, we
      observed that the TSH binding affinity for the TSHR ECD-GPI was significantly
      lower than that for the TSH holoreceptor. Further evidence for a difference in
      ligand binding kinetics for the TSH holoreceptor and TSHR ECD-GPI was obtained
      upon comparison of the TSH K(d) values for these two receptor forms at 4  degrees
      C versus room temperature. Our data provide the first evidence that the wild-type
      TSHR TMD influences ligand binding affinity for the ECD, possibly by altering the
      conformation of the closely associated hinge region that contributes to the TSH
      binding site.

PMID- 21190936
TI  - Extracellular signal-regulated kinase 8 (ERK8) controls estrogen-related receptor
      alpha (ERRalpha) cellular localization and inhibits its transcriptional activity.
AB  - ERK8 (MAPK15) is a large MAP kinase already implicated in the regulation of the
      functions of different nuclear receptors and in cellular proliferation and
      transformation. Here, we identify ERRalpha as a novel ERK8-interacting protein.
      As a consequence of such interaction, ERK8 induces CRM1-dependent translocation
      of ERRalpha to the cytoplasm and inhibits its transcriptional activity. Also, we
      identify in ERK8 two LXXLL motifs, typical of agonist-bound nuclear receptor
      corepressors, as necessary features for this MAP kinase to interact with ERRalpha
      and to regulate its cellular localization and transcriptional activity.
      Ultimately, we demonstrate that ERK8 is able to counteract, in immortalized human
      mammary cells, ERRalpha activation induced by the EGF receptor pathway, often
      deregulated in breast cancer. Altogether, these results reveal a novel function
      for ERK8 as a bona fide ERRalpha corepressor, involved in control of its cellular
      localization by nuclear exclusion, and suggest a key role for this MAP kinase in
      the regulation of the biological activities of this nuclear receptor.

PMID- 21190938
TI  - Steroid receptor co-activator is required for juvenile hormone signal
      transduction through a bHLH-PAS transcription factor, methoprene tolerant.
AB  - Metamorphosis in insects is regulated by juvenile hormone (JH) and ecdysteroids.
      The mechanism of 20-hydroxyecdysone (20E), but not of JH action, is well
      understood. A basic helix-loop-helix (bHLH)-Per-Arnt-Sim (PAS) family member,
      methoprene tolerant (Met), plays an important role in JH action. Microarray
      analysis and RNA interference (RNAi) were used to identify 69 genes that require
      Met for their hydroprene-regulated expression in the red flour beetle, Tribolium
      castaneum. Quantitative real time PCR analysis confirmed microarray data for 13
      of the 16 hydroprene-response genes tested. The members of the bHLH-PAS family
      often function as heterodimers to regulate gene expression and Met is a member of
      this family. To determine whether other members of the bHLH-PAS family are
      required for the expression of JH-response genes, we employed RNAi to knockdown
      the expression of all 11 members of the bHLH-PAS family and studied the
      expression of JH-response genes in RNAi insects. These studies showed that
      besides Met, another member of this family, steroid receptor co-activator (SRC)
      is required for the expression of 15 JH-response genes tested. Moreover, studies
      in JH responsive Aag-2 cells revealed that Aedes aegypti homologues of both Met
      and SRC are required for the expression of the JH-response gene, kr-h1, and SRC
      is required for expression of ecdysone-response genes. These data suggest the
      steroid receptor co-activator plays key roles in both JH and 20E action
      suggesting that this may be an important molecule that mediates cross-talk
      between JH and 20E to prevent metamorphosis.

PMID- 21190939
TI  - The interferon stimulated gene 54 promotes apoptosis.
AB  - The ability of interferons (IFNs) to inhibit viral replication and cellular
      proliferation is well established, but the specific contribution of each IFN
      stimulated gene (ISG) to these biological responses remains to be completely
      understood. In this report we demonstrate that ISG54, also known as IFN-induced
      protein with tetratricopeptide repeats 2 (IFIT2), is a mediator of apoptosis.
      Expression of ISG54, independent of IFN stimulation, elicits apoptotic cell
      death. Cell death and apoptosis were quantified by propidium iodide uptake and
      annexin-V staining, respectively. The activation of caspase-3, a key mediator of
      the execution phase of apoptosis, was clearly apparent in cells expressing ISG54.
      The anti-apoptotic B cell lymphoma-xl (Bcl-xl) protein inhibited the apoptotic
      effects of ISG54 as did the anti-apoptotic adenoviral E1B-19K protein. In
      addition, ISG54 was not able to promote cell death in the absence of pro
      apoptotic Bcl family members, Bax and Bak. Analyses of binding partners of ISG54
      revealed association with two homologous proteins, ISG56/IFIT1 and ISG60/IFIT3.
      In addition, ISG60 binding negatively regulates the apoptotic effects of ISG54.
      The results reveal a previously unidentified role of ISG54 in the induction of
      apoptosis via a mitochondrial pathway and shed new light on the mechanism by
      which IFN elicits anti-viral and anti-cancer effects.

PMID- 21190940
TI  - Solution structure of the guanine nucleotide-binding STAS domain of SLC26-related
      SulP protein Rv1739c from Mycobacterium tuberculosis.
AB  - The structure and intrinsic activities of conserved STAS domains of the
      ubiquitous SulP/SLC26 anion transporter superfamily have until recently remained
      unknown. Here we report the heteronuclear, multidimensional NMR spectroscopy
      solution structure of the STAS domain from the SulP/SLC26 putative anion
      transporter Rv1739c of Mycobacterium tuberculosis. The 0.87-A root mean square
      deviation structure revealed a four-stranded beta-sheet with five interspersed
      alpha-helices, resembling the anti-sigma factor antagonist fold. Rv1739c STAS was
      shown to be a guanine nucleotide-binding protein, as revealed by nucleotide
      dependent quench of intrinsic STAS fluorescence and photoaffinity labeling. NMR
      chemical shift perturbation analysis partnered with in silico docking
      calculations identified solvent-exposed STAS residues involved in nucleotide
      binding. Rv1739c STAS was not an in vitro substrate of mycobacterial kinases or
      anti-sigma factors. These results demonstrate that Rv1739c STAS binds guanine
      nucleotides at physiological concentrations and undergoes a ligand-induced
      conformational change but, unlike anti-sigma factor antagonists, may not mediate
      signals via phosphorylation.

PMID- 21190941
TI  - Asymmetric ATP hydrolysis cycle of the heterodimeric multidrug ABC transport
      complex TmrAB from Thermus thermophilus.
AB  - ATP-binding cassette (ABC) systems translocate a wide range of solutes across
      cellular membranes. The thermophilic gram-negative eubacterium Thermus
      thermophilus, a model organism for structural genomics and systems biology,
      discloses ~46 ABC proteins, which are largely uncharacterized. Here, we
      functionally analyzed the first two and only ABC half-transporters of the
      hyperthermophilic bacterium, TmrA and TmrB. The ABC system mediates uptake of the
      drug Hoechst 33342 in inside-out oriented vesicles that is inhibited by
      verapamil. TmrA and TmrB form a stable heterodimeric complex hydrolyzing ATP with
      a K(m) of 0.9 mm and k(cat) of 9 s(-1) at 68  degrees C. Two nucleotides can be
      trapped in the heterodimeric ABC complex either by vanadate or by mutation
      inhibiting ATP hydrolysis. Nucleotide trapping requires permissive temperatures,
      at which a conformational ATP switch is possible. We further demonstrate that the
      canonic glutamate 523 of TmrA is essential for rapid conversion of the ATP/ATP
      bound complex into its ADP/ATP state, whereas the corresponding aspartate in TmrB
      (Asp-500) has only a regulatory role. Notably, exchange of this single noncanonic
      residue into a catalytic glutamate cannot rescue the function of the E523Q/D500E
      complex, implicating a built-in asymmetry of the complex. However, slow ATP
      hydrolysis in the newly generated canonic site (D500E) strictly depends on the
      formation of a posthydrolysis state in the consensus site, indicating an
      allosteric coupling of both active sites.

PMID- 21190942
TI  - Triheteromeric NR1/NR2A/NR2B receptors constitute the major N-methyl-D-aspartate
      receptor population in adult hippocampal synapses.
AB  - NMDA receptors (NMDARs), fundamental to learning and memory and implicated in
      certain neurological disorders, are heterotetrameric complexes composed of two
      NR1 and two NR2 subunits. The function of synaptic NMDARs in postnatal principal
      forebrain neurons is typically attributed to diheteromeric NR1/NR2A and NR1/NR2B
      receptors, despite compelling evidence for triheteromeric NR1/NR2A/NR2B
      receptors. In synapses, the properties of triheteromeric NMDARs could thus far
      not be distinguished from those of mixtures of diheteromeric NMDARs. To find a
      signature of NR1/NR2A/NR2B receptors, we have employed two gene-targeted mouse
      lines, expressing either NR1/NR2A or NR1/NR2B receptors without NR1/NR2A/NR2B
      receptors, and compared their synaptic properties with those of wild type. In
      acute hippocampal slices of mutants older than 4 weeks we found a distinct
      voltage dependence of NMDA R-mediated excitatory postsynaptic current (NMDA EPSC)
      decay time for the two diheteromeric NMDARs. In wild-type mice, NMDA EPSCs
      unveiled the NR1/NR2A characteristic for this voltage-dependent deactivation
      exclusively, indicating that the contribution of NR1/NR2B receptors to evoked
      NMDA EPSCs is negligible in adult CA3-to-CA1 synapses. The presence of
      NR1/NR2A/NR2B receptors was obvious from properties that could not be explained
      by a mixture of diheteromeric NR1/NR2A and NR1/NR2B receptors or by the presence
      of NR1/NR2A receptors alone. The decay time for NMDA EPSCs in wild type was
      slower than that for NR1/NR2A receptors, and the sensitivity of NMDA EPSCs to
      NR2B-directed NMDAR antagonists was 50%. Thus, NR2B is prominent in adult
      hippocampal synapses as an integral part of NR1/NR2A/NR2B receptors.

PMID- 21190943
TI  - Reduced sodium channel Na(v)1.1 levels in BACE1-null mice.
AB  - The Alzheimer BACE1 enzyme cleaves numerous substrates, with largely unknown
      physiological consequences. We have previously identified the contribution of
      elevated BACE1 activity to voltage-gated sodium channel Na(v)1.1 density and
      neuronal function. Here, we analyzed physiological changes in sodium channel
      metabolism in BACE1-null mice. Mechanistically, we first confirmed that
      endogenous BACE1 requires its substrate, the beta-subunit Na(v)beta(2), to
      regulate levels of the pore-forming alpha-subunit Na(v)1.1 in cultured primary
      neurons. Next, we analyzed sodium channel alpha-subunit levels in brains of BACE1
      null mice at 1 and 3 months of age. At both ages, we found that Na(v)1.1 protein
      levels were significantly decreased in BACE1-null versus wild-type mouse brains,
      remaining unchanged in BACE1-heterozygous mouse brains. Interestingly, levels of
      Na(v)1.2 and Na(v)1.6 alpha-subunits also decreased in 1-month-old BACE1-null
      mice. In the hippocampus of BACE1-null mice, we found a robust 57% decrease of
      Na(v)1.1 levels. Next, we performed surface biotinylation studies in acutely
      dissociated hippocampal slices from BACE1-null mice. Hippocampal surface Na(v)1.1
      levels were significantly decreased, but Na(v)1.2 surface levels were increased
      in BACE1-null mice perhaps as a compensatory mechanism for reduced surface
      Na(v)1.1. We also found that Na(v)beta(2) processing and Na(v)1.1 mRNA levels
      were significantly decreased in brains of BACE1-null mice. This suggests a
      mechanism consistent with BACE1 activity regulating mRNA levels of the alpha
      subunit Na(v)1.1 via cleavage of cell-surface Na(v)beta(2). Together, our data
      show that endogenous BACE1 activity regulates total and surface levels of voltage
      gated sodium channels in mouse brains. Both decreased Na(v)1.1 and elevated
      surface Na(v)1.2 may result in a seizure phenotype. Our data caution that
      therapeutic BACE1 activity inhibition in Alzheimer disease patients may affect
      Na(v)1 metabolism and alter neuronal membrane excitability in Alzheimer disease
      patients.

PMID- 21190944
TI  - Transcriptional regulation by Asf1: new mechanistic insights from studies of the
      DNA damage response to replication stress.
AB  - Asf1 is a conserved histone H3/H4 chaperone. We find that Asf1 in budding yeast
      promotes an essential cellular response to replication stress caused by the
      ribonucleotide reductase inhibitor hydroxyurea. That is, Asf1 stimulates
      derepression of DNA damage response (DDR) genes during the S phase. Derepression
      of DDR genes strongly correlates with Asf1 binding to their promoters. Having
      identified the C terminus and histone-binding domains of Asf1 as molecular
      determinants of its constitutive and inducible association with chromatin, we
      tested whether Asf1 binding to DDR genes is mechanistically important for their
      derepression. Our results provide little support for this hypothesis. Rather, the
      contribution of Asf1 to DDR gene derepression depends on its ability to stimulate
      H3K56 acetylation by lysine acetyltransferase Rtt109. The precise regulation of
      H3K56 acetylation in the promoters of DDR genes is unexpected: DDR gene promoters
      are occupied by H3K56-acetylated nucleosomes under repressing conditions, and the
      steady state level of H3K56 promoter acetylation does not change upon
      derepression. We propose that replication-coupled deposition of Lys(56)
      acetylated H3 poises the DDR genes in newly synthesized daughter duplexes for
      derepression during the S phase. In this model, the presence of a histone mark
      that destabilizes nucleosomes is compatible with suppression of transcription
      because in the uninduced state, DDR gene promoters are constitutively occupied by
      a potent repressor-corepressor complex.

PMID- 21190945
TI  - Bleomycin hydrolase is regulated biphasically in a differentiation- and cytokine
      dependent manner: relevance to atopic dermatitis.
AB  - Loss-of-function mutation in the profilaggrin gene is a major risk factor for
      atopic dermatitis (AD). Previously, we showed that a neutral cysteine protease,
      bleomycin hydrolase (BH), has a role in generating natural moisturizing factors,
      and calpain I is an upstream protease in the filaggrin degradation pathway. Here,
      we investigated the transcriptional regulatory mechanisms of BH and the relevance
      of BH to AD. First, we cloned the 5'-flanking region of BH. Deletion analyses
      identified a critical region for BH promoter activity within -216 bp upstream.
      Electrophoretic mobility shift assay revealed that MZF-1, Sp-1, and interferon
      regulatory factor-1/2 could bind to this region in vitro. Moreover, site-directed
      mutagenesis of the MZF-1 and Sp-1 motifs markedly reduced BH promoter activity.
      These data indicate that BH expression is up-regulated via MZF-1 and Sp-1.
      Interestingly, a Th1 cytokine, IFN-gamma, significantly reduced the expression of
      BH. Analyses with site-directed mutagenesis and small interference RNA supported
      the suppressing effect of IFN-gamma on BH expression. On the other hand, a Th2
      cytokine, IL-4, did not show any direct effect on BH expression. However, it down
      regulated MZF-1 and Sp-1 in cultured keratinocytes, indicating that IL-4 could
      work as a suppressor in BH regulation. Lastly, we examined expression of BH in
      skins of patients with AD. BH activity and expression were markedly decreased in
      AD lesional skin, suggesting a defect of the filaggrin degradation pathway in AD.
      Our results suggest that BH transcription would be modulated during both
      differentiation and inflammation.

PMID- 21190946
TI  - Caregiver evaluation in hospice: application of a semi-structured interview.
AB  - In this study we report the results of construction and administration of a semi
      structured interview for the evaluation of caregivers in hospice. The results
      presented here are related to interviews (n = 25) that were administered at
      Rimini Hospice. According to the interview coding system, it was possible to
      identify thematic areas of the interviews where the caregiver's distress was
      mainly concentrated. As concerning the care burden, greater distress was detected
      in areas relating to the change in the rhythm of life (38%) and in social network
      (26%); whereas, as concerning the psychological burden, a greater distress was
      detected in the area related to the caregiver role (51%). In conclusion, a
      singular element identified as a source of distress in, our study, is that of
      social network.

PMID- 21190947
TI  - Cross-cultural communication and use of the family meeting in palliative care.
AB  - Terminally-ill patients and their families often report poor communication and
      limited understanding of the patient's diagnosis, prognosis, and treatment plan;
      these deficits can be exacerbated by cross-cultural issues. Although family
      meetings are frequently recommended to facilitate provider-family communication,
      a more structured, evidence-based approach to their use may improve outcomes.
      Drawing on research and guidelines from critical care, palliative care, and cross
      cultural communication, we propose a framework for conducting family meetings
      with consideration for cross-cultural issues.

PMID- 21190948
TI  - Genomic and nongenomic stimulatory effect of aldosterone on H+-ATPase in proximal
      S3 segments.
AB  - The genomic and nongenomic effects of aldosterone on the intracellular pH
      recovery rate (pHirr) via H(+)-ATPase and on cytosolic free calcium concentration
      ([Ca(2+)](i)) were investigated in isolated proximal S3 segments of rats during
      superfusion with an Na(+)-free solution, by using the fluorescent probes BCECF-AM
      and FLUO-4-AM, respectively. The pHirr, after cellular acidification with a
      NH(4)Cl pulse, was 0.064 +/- 0.003 pH units/min (n = 17/74) and was abolished
      with concanamycin. Aldosterone (10(-12), 10(-10), 10(-8), or 10(-6) M with 1-h or
      15- or 2-min preincubation) increased the pHirr. The baseline [Ca(2+)](i) was 103
      +/- 2 nM (n = 58). After 1 min of aldosterone preincubation, there was a
      transient and dose-dependent increase in [Ca(2+)](i) and after 6-min
      preincubation there was a new increase in [Ca(2+)](i) that persisted after 1 h.
      Spironolactone [mineralocorticoid (MR) antagonist], actinomycin D, or
      cycloheximide did not affect the effects of aldosterone (15- or 2-min
      preincubation) on pHirr and on [Ca(2+)](i) but inhibited the effects of
      aldosterone (1-h preincubation) on these parameters. RU 486 [glucocorticoid (GR)
      antagonist] and dimethyl-BAPTA (Ca(2+) chelator) prevented the effect of
      aldosterone on both parameters. The data indicate a genomic (1 h, via MR) and a
      nongenomic action (15 or 2 min, probably via GR) on the H(+)-ATPase and on
      [Ca(2+)](i). The results are compatible with stimulation of the H(+)-ATPase by
      increases in [Ca(2+)](i) (at 10(-12)-10(-6) M aldosterone) and inhibition of the
      H(+)-ATPase by decreases in [Ca(2+)](i) (at 10(-12) or 10(-6) M aldosterone plus
      RU 486).

PMID- 21190949
TI  - A mathematical model of the myogenic response to systolic pressure in the
      afferent arteriole.
AB  - Elevations in systolic blood pressure are believed to be closely linked to the
      pathogenesis and progression of renal diseases. It has been hypothesized that the
      afferent arteriole (AA) protects the glomerulus from the damaging effects of
      hypertension by sensing increases in systolic blood pressure and responding with
      a compensatory vasoconstriction (Loutzenhiser R, Bidani A, Chilton L. Circ Res
      90: 1316-1324, 2002). To investigate this hypothesis, we developed a mathematical
      model of the myogenic response of an AA wall, based on an arteriole model
      (Gonzalez-Fernandez JM, Ermentrout B. Math Biosci 119: 127-167, 1994). The model
      incorporates ionic transport, cell membrane potential, contraction of the AA
      smooth muscle cell, and the mechanics of a thick-walled cylinder. The model
      represents a myogenic response based on a pressure-induced shift in the voltage
      dependence of calcium channel openings: with increasing transmural pressure,
      model vessel diameter decreases; and with decreasing pressure, vessel diameter
      increases. Furthermore, the model myogenic mechanism includes a rate-sensitive
      component that yields constriction and dilation kinetics similar to behaviors
      observed in vitro. A parameter set is identified based on physical dimensions of
      an AA in a rat kidney. Model results suggest that the interaction of Ca(2+) and
      K(+) fluxes mediated by voltage-gated and voltage-calcium-gated channels,
      respectively, gives rise to periodicity in the transport of the two ions. This
      results in a time-periodic cytoplasmic calcium concentration, myosin light chain
      phosphorylation, and cross-bridge formation with the attending muscle stress.
      Furthermore, the model predicts myogenic responses that agree with experimental
      observations, most notably those which demonstrate that the renal AA constricts
      in response to increases in both steady and systolic blood pressures. The
      myogenic model captures these essential functions of the renal AA, and it may
      prove useful as a fundamental component in a multiscale model of the renal
      microvasculature suitable for investigations of the pathogenesis of hypertensive
      renal diseases.

PMID- 21190951
TI  - Indicators for follow-up of multidisciplinary teamwork in care processes: results
      of an international expert panel.
AB  - In order to study the impact of interventions on multidisciplinary teamwork in
      care processes, relevant indicators need to be defined. In the present study, the
      authors performed a Delphi survey of a purposively selected expert panel
      consisting of scientific researchers and hospital managers. Thirty-six experts
      from 13 countries participated. Each participant rated a list of team indicators
      on a scale of 1-6. Consensus was sought in two consecutive rounds. The content
      validity index (CVI) varied from 8% to 92%. A final list of 19 indicators was
      generated: 5 on team context/structure, 8 on team process, and 6 on team
      outcomes. Most relevant team indicators were as follows: "team relations,"
      "quality of team leadership," "culture/climate for teamwork," "team perceived
      coordination of the care process," and "team vision." Scientific researchers and
      hospital managers that want to study and improve multidisciplinary teamwork in
      care processes should primarily focus on these team indicators.

PMID- 21190950
TI  - Renal sodium transporter/channel expression and sodium excretion in P2Y2 receptor
      knockout mice fed a high-NaCl diet with/without aldosterone infusion.
AB  - The P2Y(2) receptor (P2Y2-R) antagonizes sodium reabsorption in the kidney. Apart
      from its effect in distal nephron, hypothetically, P2Y(2)-R may modulate
      activity/abundances of sodium transporters/channel subunits along the nephron via
      antagonism of aldosterone or vasopressin or interaction with mediators such as
      nitric oxide (NO), and prostaglandin E(2) (PGE(2)) or oxidative stress (OS). To
      determine the extent of the regulatory role of P2Y(2)-R in renal sodium
      reabsorption, in study 1, we fed P2Y(2)-R knockout (KO; n = 5) and wild-type (WT;
      n = 5) mice a high (3.15%)-sodium diet (HSD) for 14 days. Western blotting
      revealed significantly higher protein abundances for cortical and medullary
      bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2), medullary alpha-1-subunit of
      Na-K-ATPase, and medullary alpha-subunit of the epithelial sodium channel (ENaC)
      in KO vs. WT mice. Molecular analysis of urine showed increased excretion of
      nitrates plus nitrites (NOx), PGE(2), and 8-isoprostane in the KO, relative to WT
      mice, supporting a putative role for these molecules in determining alterations
      of proteins involved in sodium transport along the nephron. To determine whether
      genotype differences in response to aldosterone might have played a role in these
      differences due to HSD, in study 2 aldosterone levels were clamped (by osmotic
      minipump infusion). Clamping aldosterone (with HSD) led to significantly impaired
      natriuresis with elevated Na/H exchanger isoform 3 in the cortex, and NKCC2 in
      the medulla, and modest but significantly lower levels of NKCC2, and alpha- and
      beta-ENaC in the cortex of KO vs. WT mice. This was associated with significantly
      reduced urinary NOx in the KO, although PGE(2) and 8-isoprostane remained
      significantly elevated vs. WT mice. Taken together, our results suggest that
      P2Y(2)-R is an important regulator of sodium transporters along the nephron. Pre-
      or postreceptor differences in the response to aldosterone, perhaps mediated via
      prostaglandins or changes in NOS activity or OS, likely play a role.

PMID- 21190952
TI  - Surveying ourselves: examining the use of a web-based approach for a physician
      survey.
AB  - A survey was distributed, using a sequential mixed-mode approach, to a national
      sample of obstetrician-gynecologists. Differences between responses to the web
      based mode and the on-paper mode were compared to determine if there were
      systematic differences between respondents. Only two differences in respondents
      between the two modes were identified. University-based physicians were more
      likely to complete the web-based mode than private practice physicians. Mail
      respondents reported a greater volume of endometrial ablations compared to online
      respondents. The web-based mode had better data quality than the paper-based
      mailed mode in terms of less missing and inappropriate responses. Together, these
      findings suggest that, although a few differences were identified, the web-based
      survey mode attained adequate representativeness and improved data quality. Given
      the metrics examined for this study, exclusive use of web-based data collection
      may be appropriate for physician surveys with a minimal reduction in sample
      coverage and without a reduction in data quality.

PMID- 21190953
TI  - Chemopreventive effect of Curcuma longa Linn on liver pathology in HBx transgenic
      mice.
AB  - Unlike other forms of hepatocellular carcinoma (HCC), HCC induced by hepatitis B
      virus (HBV) infection shows a poor prognosis after conventional therapies. HBV
      induces liver cirrhosis and HCC. Many researchers have made efforts to find new
      substances that suppress the activity of HBV. Curcuma longa Linn (CLL) has been
      used for traditional medicine and food in Asia, especially in India, and has
      shown chemopreventive effects in a HBV-related in vitro model. This in vivo study
      was designed to seek the chemopreventive effects of CLL and its mechanisms. CLL
      mixture concentrated with dextrose water by boiling was lyophilized. CLL extracts
      were administrated to HBV X protein (HBx) transgenic mice aged 4 weeks for 2 to 4
      weeks and aged 6 months for 3 months. After administration, histological changes
      in the liver tissue and expression of HBx-related genes were investigated. CLL
      treated mice showed less visceral fat, a smaller liver/body weight ratio and
      delayed liver pathogenesis. Proliferating cell nuclear antigen (PCNA) expression
      was also increased in CLL-treated HBx transgenic mice, indicating regeneration of
      damaged liver tissue. CLL treatment decreased expression of HBx and increased p21
      and cyclin D1 in livers of HBx transgenic mice. In addition, p-p53 was increased
      after CLL treatment. These results suggest that CLL can have beneficial effects
      on the early and late stages of liver pathogenesis, preventing and delaying liver
      carcinogenesis. This drug should be considered as a potential chemopreventive
      agent for HBV-related hepatocarcinogenesis.

PMID- 21190954
TI  - Endocrine disruption of brain sexual differentiation by developmental PCB
      exposure.
AB  - In mammals, sexual differentiation of the hypothalamus occurs during prenatal and
      early postnatal development due in large part to sex differences in hormones.
      These early organizational processes are critically important for the attainment
      and maintenance of adult reproductive functions. We tested the hypothesis that
      perinatal exposure to polychlorinated biphenyls (PCBs) that disrupt hormonal
      pathways would perturb reproductive maturation and the sexually dimorphic
      development of neuroendocrine systems in the preoptic area (POA). Pregnant
      Sprague-Dawley rats were injected on gestational d 16 and 18 with vehicle
      (dimethylsulfoxide), Aroclor 1221 (A1221, an estrogenic PCB mix), a reconstituted
      PCB mixture representing those highest in human body burden (PCBs 138, 153, 180),
      or estradiol benzoate, an estrogenic control. Male and female pups were monitored
      for somatic and reproductive development. In adulthood, some rats were perfused
      and used for immunohistochemistry of estrogen receptor alpha, kisspeptin, and
      coexpression of Fos in GnRH neurons. Other rats were used to obtain fresh-frozen
      POA dissections for use in a PCR-based 48-gene expression array. Pubertal onset
      was advanced and estrous cyclicity irregular in endocrine-disrupted females.
      Furthermore, sexual differentiation of female neuroendocrine systems was
      masculinized/defeminized. Specifically, in the adult female anteroventral
      periventricular nucleus, estrogen receptor alpha-cell numbers and kisspeptin
      fiber density were significantly decreased, as was GnRH-Fos coexpression. PCR
      analysis identified androgen receptor, IGF-I, N-methyl-d-aspartate receptor
      subunit NR2b, and TGFbeta1 mRNAs as significantly down-regulated in endocrine
      disrupted female POAs. These data suggest that developmental PCBs profoundly
      impair the sexual differentiation of the female hypothalamus.

PMID- 21190955
TI  - Aldosterone/Mineralocorticoid receptor stimulation induces cellular senescence in
      the kidney.
AB  - Recent studies demonstrated a possible role of aldosterone in mediating cell
      senescence. Thus, the aim of this study was to investigate whether aldosterone
      induces cell senescence in the kidney and whether aldosterone-induced renal
      senescence affects the development of renal injury. Aldosterone infusion (0.75
      MUg/h) into rats for 5 weeks caused hypertension and increased urinary excretion
      rates of proteins and N-acetyl-beta-D-glucosaminidase. Aldosterone induced
      senescence-like changes in the kidney, exhibited by increased expression of the
      senescence-associated beta-galactosidase, overexpression of p53 and cyclin
      dependent kinase inhibitor (p21), and decreased expression of SIRT1. These
      changes were abolished by eplerenone (100 mg/kg/d), a mineralocorticoid receptor
      (MR) antagonist, but unaffected by hydralazine (80 mg/liter in drinking water).
      Furthermore, aldosterone induced similar changes in senescence-associated beta
      galactosidase, p21, and SIRT1 expression in cultured human proximal tubular
      cells, which were normalized by an antioxidant, N-acetyl L-cysteine, or gene
      silencing of MR. Aldosterone significantly delayed wound healing and reduced the
      number of proliferating human proximal tubular cells, while gene silencing of p21
      diminished the effects, suggesting impaired recovery from tubular damage. These
      findings indicate that aldosterone induces renal senescence in proximal tubular
      cells via the MR and p21-dependent pathway, which may be involved in aldosterone
      induced renal injury.

PMID- 21190956
TI  - Prevention of DNA double-strand breaks induced by radioiodide-(131)I in FRTL-5
      thyroid cells.
AB  - Radioiodine-131 released from nuclear reactor accidents has dramatically
      increased the incidence of papillary thyroid cancer in exposed individuals. The
      deposition of ionizing radiation in cells results in double-strand DNA breaks
      (DSB) at fragile sites, and this early event can generate oncogenic
      rearrangements that eventually cause cancer. The aims of this study were to
      develop a method to show DNA DSBs induced by (131)I in thyroid cells; to test
      monovalent anions that are transported by the sodium/iodide symporter to
      determine whether they prevent (131)I-induced DSB; and to test other
      radioprotective agents for their effect on irradiated thyroid cells. Rat FRTL-5
      thyroid cells were incubated with (131)I. DSBs were measured by nuclear
      immunofluorescence using antibodies to p53-binding protein 1 or gammaH2AX.
      Incubation with 1-10 MUCi (131)I per milliliter for 90 min resulted in a dose
      related increase of DSBs; the number of DSBs increased from a baseline of 4-15%
      before radiation to 65-90% after radiation. GH3 or CHO cells that do not
      transport iodide did not develop DSBs when incubated with (131)I. Incubation with
      20-100 MUm iodide or thiocyanate markedly attenuated DSBs. Perchlorate was about
      6 times more potent than iodide or thiocyanate(.) The effects of the anions were
      much greater when each was added 30-120 min before the (131)I. Two natural
      organic compounds recently shown to provide radiation protection partially
      prevented DSBs caused by (131)I and had an additive effect with perchlorate. In
      conclusion, we developed a thyroid cell model to quantify the mitogenic effect of
      (131)I. (131)I causes DNA DSBs in FRTL-5 cells and had no effect on cells that do
      not transport iodide. Perchlorate, iodide, and thiocyanate protect against DSBs
      induced by (131)I.

PMID- 21190957
TI  - Is the vitamin d receptor found in muscle?
AB  - The active form of vitamin D, 1alpha,25-dihydroxyvitamin D(3), is critical for
      the regulation of serum calcium and phosphorus levels that in turn support bone
      mineralization and neuromuscular activity. It is well known that vitamin D
      deficiency causes rachitic/osteomalacic myopathy and cardiac disorder and the
      provision of vitamin D can reverse the symptoms. However, the underlying
      mechanisms remain unclear. The question of whether the vitamin D receptor is
      found in muscle has been debated but not settled. We recently studied all
      available antibodies against the vitamin D receptor and found that most
      antibodies used detect proteins other than the vitamin D receptor, and therefore,
      the utility of these antibodies may generate the false-positive results. Using
      antibodies that do not detect proteins in tissues from vitamin D receptor null
      mice, we have developed a specific and sensitive immunohistochemical assay. The
      results from this investigation show that the vitamin D receptor is undetectable
      in skeletal, cardiac, and smooth muscle, suggesting that the function of vitamin
      D on muscle is either of an indirect nature or does not involve the known
      receptor.

PMID- 21190958
TI  - Circadian control of kisspeptin and a gated GnRH response mediate the
      preovulatory luteinizing hormone surge.
AB  - In spontaneously ovulating rodents, the preovulatory LH surge is initiated on the
      day of proestrus by a timed, stimulatory signal originating from the circadian
      clock in the suprachiasmatic nucleus (SCN). The present studies explored whether
      kisspeptin is part of the essential neural circuit linking the SCN to the GnRH
      system to stimulate ovulation in Syrian hamsters (Mesocricetus auratus).
      Kisspeptin neurons exhibit an estrogen-dependent, daily pattern of cellular
      activity consistent with a role in the circadian control of the LH surge. The SCN
      targets kisspeptin neurons via vasopressinergic (AVP), but not vasoactive
      intestinal polypeptide-ergic, projections. Because AVP administration can only
      stimulate the LH surge during a restricted time of day, we examined the
      possibility that the response to AVP is gated at the level of kisspeptin and/or
      GnRH neurons. Kisspeptin and GnRH activation were assessed after the
      administration of AVP during the morning (when AVP is incapable of initiating the
      LH surge) and the afternoon (when AVP injections stimulate the LH surge).
      Kisspeptin, but not GnRH, cellular activity was up-regulated after morning
      injections of AVP, suggesting that time-dependent sensitivity to SCN signaling is
      gated within GnRH but not kisspeptin neurons. In support of this possibility, we
      found that the GnRH system exhibits pronounced daily changes in sensitivity to
      kisspeptin stimulation, with maximal sensitivity in the afternoon. Together these
      studies reveal a novel mechanism of ovulatory control with interactions among the
      circadian system, kisspeptin signaling, and a GnRH gating mechanism of control.

PMID- 21190959
TI  - Dissociation of epidermal growth factor receptor and ErbB2 heterodimers in the
      presence of somatostatin receptor 5 modulate signaling pathways.
AB  - Epidermal growth factor through the stimulation of epidermal growth factor
      receptor (EGFR) plays a critical role in the activation of MAPKs and
      phosphatidylinositol-3-protein kinase/AKT cell survival pathways attributed in
      many pathological conditions. At the cellular level, such functions involve EGFR
      overactivation and phosphorylation. In the present study, we describe that human
      embryonic kidney-293 cells transfected with somatostatin (SST) receptor 5 (SSTR5)
      exhibit inhibition of EGFR phosphorylation and modulate MAPK and
      phosphatidylinositol-3-protein kinase/AKT cell survival signaling. Furthermore,
      suppression of EGFR by using small interference RNA and an antagonist (AG1478)
      potentiates the SST effect via activation of SSTR5 on signaling molecules. In
      wild-type human embryonic kidney-293 cells, EGFR/ErbB2 exists as constitutive
      heterodimers. The presence of SSTR5 leads to the dissociation of the heteromeric
      complex of EGFR/ErbB2 and display preferential heterodimerization between SSTR5
      and EGFR in an agonist-dependent manner. These findings highlight a new
      undiscovered mechanism and potential role of SSTR5 to attenuate the EGFR-mediated
      signaling pathways involved in tumorigenesis. Our data indicate that the
      activation and/or overexpression of SST receptors along with the inhibition of
      EGFR will serve as an important therapeutic approach in the treatment of ErbB
      positive tumors.

PMID- 21190960
TI  - Hnrnpk, a protein differentially expressed in immature rat ovarian development,
      is required for normal primordial follicle assembly and development.
AB  - The formation of ovarian follicles and subsequent development after birth are
      critical processes for female reproduction, and inappropriate coordination of
      these processes contributes to ovarian pathologies, such as premature ovarian
      failure and infertility. Identification and functional investigation of the
      factors involved in follicular assembly and the initial recruitment will be of
      great significance to the understanding of the female reproduction process. In
      this study, we examined the roles of transcription factor heterogeneous nuclear
      ribonucleoprotein K (Hnrnpk) in rat primordial folliculogenesis using RNA
      interference knockdown strategies. Reducing Hnrnpk mRNA levels via Hnrnpk small
      interfering RNAs to neonatal ovaries resulted in a substantial loss of naked
      oocytes, primordial and primary follicles. Structure disorganization of the ovary
      characterized by groups of oocytes arranged in nests, clusters of somatic cells
      not associated with any oocytes and many highly condensed oocyte nuclei was
      observed. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick
      end labeling assay demonstrated that these abnormalities may be partially
      attributable to abnormal apoptosis of oocytes. Furthermore, the microarray
      analysis showed that 63 genes changed significantly (>=2-folds or <=0.5-fold)
      between the ovaries treated with Hnrnpk small interfering RNAs and the controls,
      with 22 up-regulated genes and 41 down-regulated genes. These differentially
      expressed genes were involved in several critical biological processes in ovarian
      development. These results suggest that transcription factor Hnrnpk is a key
      regulator for primordial follicle assembly and development, which provides a new
      potential therapeutic target to regulate ovarian function and treat ovarian
      disease.

PMID- 21190961
TI  - The transcription factor B-cell lymphoma (BCL)-6 modulates pancreatic {beta}-cell
      inflammatory responses.
AB  - Type 1 diabetes is a chronic autoimmune disease with a strong inflammatory
      component. We have previously shown that expression of the transcriptional
      repressor B-cell lymphoma (BCL)-6 is very low in pancreatic beta-cells, which may
      favor prolonged proinflammatory responses after exposure to the cytokines IL
      1beta and interferon gamma. Here we investigated whether cytokine-induced
      inflammation and apoptosis can be prevented in beta-cells by BCL-6 expression
      using plasmid, prolactin, and adenoviral approaches. The induction of mild or
      abundant BCL-6 expression in beta-cells by prolactin or an adenoviral BCL-6
      expression construct, respectively, reduced cytokine-induced inflammatory
      responses in a dose-dependent manner through inhibition of nuclear factor-kappaB
      activation. BCL-6 decreased Fas and inducible nitric oxide synthase expression
      and nitric oxide production, but it inhibited the expression of the antiapoptotic
      proteins Bcl-2 and JunB while increasing the expression of the proapoptotic death
      protein 5. The net result of these opposite effects was an augmentation of beta
      cell apoptosis. In conclusion, BCL-6 expression tones down the unrestrained
      cytokine-induced proinflammatory response of beta-cells but it also favors gene
      networks leading to apoptosis. This suggests that cytokine-induced
      proinflammatory and proapoptotic signals can be dissociated in beta-cells.
      Further understanding of these pathways may open new possibilities to improve
      beta-cell survival in early type 1 diabetes or after transplantation.

PMID- 21190962
TI  - Respiratory syncytial virus represses glucocorticoid receptor-mediated gene
      activation.
AB  - Respiratory syncytial virus (RSV) is a common cause of bronchiolitis in infants.
      Although antiinflammatory in nature, glucocorticoids have been shown to be
      ineffective in the treatment of RSV-induced bronchiolitis and wheezing. In
      addition, the effectiveness of glucocorticoids at inhibiting RSV-induced
      proinflammatory cytokine production in cell culture has been questioned. In this
      study, we have investigated the effect of RSV infection on glucocorticoid-induced
      gene activation in lung epithelium-derived cells. We show that RSV infection
      inhibits dexamethasone induction of three glucocorticoid receptor (GR)-regulated
      genes (glucocorticoid-inducible leucine zipper, FK506 binding protein, and MAPK
      phosphatase 1) in A549, BEAS-2B cells, and primary small airway epithelial cells.
      UV irradiation of the virus prevents this repression, suggesting that viral
      replication is required. RSV is known to activate the nuclear factor kappaB
      (NFkappaB) pathway, which is mutually antagonistic towards the GR pathway.
      However, specific inhibition of NFkappaB had no effect on the repression of GR
      induced genes by RSV infection, indicating that RSV repression of GR is
      independent of NFkappaB. RSV infection of A549 cells does not alter GR protein
      levels or GR nuclear translocation but does reduce GR binding to the promoters of
      the glucocorticoid responsive genes analyzed in this study. Repression of GR by
      RSV infection may account for the apparent clinical ineffectiveness of
      glucocorticoids in RSV bronchiolitis therapy. In addition, this data adds to our
      previously published data suggesting that GR may be a general target for
      infectious agents. Identifying the mechanisms through which this suppression
      occurs may lead to the development of novel therapeutics.

PMID- 21190963
TI  - Loss of canonical insulin signaling accelerates vascular smooth muscle cell
      proliferation and migration through changes in p27Kip1 regulation.
AB  - Insulin resistance is associated with an accelerated rate of atherosclerosis.
      Vascular smooth muscle cell (VSMC) migration and proliferation are important
      components of atherosclerosis. To elucidate the effects of the loss of normal
      insulin receptor (IR) signaling on VSMC function, we compared the proliferation
      and migration of murine VSMCs lacking the IR (L2-VSMCs) with wild type (WT
      VSMCs). We also examined changes in the response of L2-VSMCs to insulin
      stimulation and to inhibition of the mammalian target of rapamycin (mTOR), a
      kinase critical in VSMC proliferation and migration. The L2-VSMCs exhibit greater
      proliferation and migration rates compared with WT-VSMCs. L2-VSMCs also exhibit a
      resistance to the effects of rapamycin, an mTOR inhibitor, on proliferation,
      migration, and cell cycle progression. The resistance to mTOR inhibition is
      coupled with a loss of effect on the cyclin-dependent kinase inhibitor p27(Kip1),
      an inhibitor of cell cycle progression and VSMC migration. In response to
      stimulation with physiological insulin, the L2-VSMCs exhibit a loss of Akt
      phosphorylation and a significantly increased activation of the ERK-1/2 compared
      with WT-VSMCs. Insulin stimulation also decreased p27(Kip1) mRNA in L2-VSMCs but
      not in WT-VSMCs. The effect of insulin on p27(Kip1) mRNA was blocked by
      pretreatment with an ERK-1/2 pathway inhibitor. We conclude that loss of
      canonical insulin signaling results in increased ERK-1/2 activation in response
      to physiological insulin that decreases p27(Kip1) mRNA. These data demonstrate a
      potential mechanism where changes in IR signaling could lead to a decrease in
      p27(Kip1), accelerating VSMC proliferation and migration.

PMID- 21190964
TI  - Prevention of Leishmania donovani infection.

PMID- 21190965
TI  - Longlasting insecticidal nets for prevention of Leishmania donovani infection in
      India and Nepal: paired cluster randomised trial.
AB  - OBJECTIVE: To test the effectiveness of large scale distribution of longlasting
      nets treated with insecticide in reducing the incidence of visceral leishmaniasis
      in India and Nepal. DESIGN: Paired cluster randomised controlled trial designed
      to detect a 50% reduction in incidence of Leishmania donovani infection. SETTING:
      Villages in Muzaffarpur district in India and Saptari, Sunsari, and Morang
      districts in Nepal. PARTICIPANTS: 13 intervention and 13 control clusters. 12 691
      people were included in the analysis of the main outcome (infection), and 19 810
      were enrolled for the secondary (disease) end point. INTERVENTION: Longlasting
      insecticidal nets (treated with deltamethrin) were distributed in the
      intervention clusters in December 2006. MAIN OUTCOME MEASURES: Infection was
      determined by direct agglutination test at 12 and 24 months after the
      intervention in those who had negative results (titre <1:1600) at baseline. The
      effect estimate was computed as the geometric mean of the risk ratios for
      seroconversion for each cluster pair (net/no net), with its 95% confidence
      interval. Formal tests of effect of no intervention were obtained with a paired t
      test. RESULTS: There was no significant difference in the risk of seroconversion
      over 24 months in intervention (5.4%; 347/6372) compared with control (5.5%;
      345/6319 people) clusters (risk ratio 0.90, 95% confidence interval 0.49 to 1.65)
      nor in the risk of clinical visceral leishmaniasis (0.99, 0.46 to 1.40).
      Adjustment for covariates did not alter these conclusions. CONCLUSIONS: There is
      no evidence that large scale distribution of longlasting insecticidal nets
      provides additional protection against visceral leishmaniasis compared with
      existing control practice in the Indian subcontinent. The observed effect was
      small and not significant, though the confidence intervals did not exclude a 50%
      change in either direction. TRIAL REGISTRATION: Clinical Trials NCT 2005-015374.

PMID- 21190967
TI  - Treatment of periodontal disease in pregnancy.

PMID- 21190968
TI  - Diagnosis and management of soft tissue sarcoma.

PMID- 21190966
TI  - Obstetric outcomes after treatment of periodontal disease during pregnancy:
      systematic review and meta-analysis.
AB  - OBJECTIVE: To examine whether treatment of periodontal disease with scaling and
      root planing during pregnancy is associated with a reduction in the preterm birth
      rate. DESIGN: Systematic review and meta-analysis of randomised controlled
      trials. DATA SOURCES: Cochrane Central Trials Registry, ISI Web of Science,
      Medline, and reference lists of relevant studies to July 2010; hand searches in
      key journals. STUDY SELECTION: Randomised controlled trials including pregnant
      women with documented periodontal disease randomised to either treatment with
      scaling and root planing or no treatment. DATA EXTRACTION: Data were extracted by
      two independent investigators, and a consensus was reached with the involvement a
      third. Methodological quality of the studies was assessed with the Cochrane's
      risk of bias tool, and trials were considered either high or low quality. The
      primary outcome was preterm birth (<37 weeks). Secondary outcomes were low
      birthweight infants (<2500 g), spontaneous abortions/stillbirths, and overall
      adverse pregnancy outcome (preterm birth <37 weeks and spontaneous
      abortions/stillbirths). RESULTS: 11 trials (with 6558 women) were included. Five
      trials were considered to be of high methodological quality (low risk of bias),
      whereas the rest were low quality (high or unclear risk of bias). Results among
      low and high quality trials were consistently diverse; low quality trials
      supported a beneficial effect of treatment, and high quality trials provided
      clear evidence that no such effect exists. Among high quality studies, treatment
      had no significant effect on the overall rate of preterm birth (odds ratio 1.15,
      95% confidence interval 0.95 to 1.40; P=0.15). Furthermore, treatment did not
      reduce the rate of low birthweight infants (odds ratio 1.07, 0.85 to 1.36;
      P=0.55), spontaneous abortions/stillbirths (0.79, 0.51 to 1.22; P=0.28), or
      overall adverse pregnancy outcome (preterm births <37 weeks and spontaneous
      abortions/stillbirths) (1.09, 0.91 to 1.30; P=0.34). CONCLUSION: Treatment of
      periodontal disease with scaling and root planing cannot be considered to be an
      efficient way of reducing the incidence of preterm birth. Women may be advised to
      have periodical dental examinations during pregnancy to test their dental status
      and may have treatment for periodontal disease. However, they should be told that
      such treatment during pregnancy is unlikely to reduce the risk of preterm birth
      or low birthweight infants.

PMID- 21190969
TI  - Spain votes to ban smoking in public places.

PMID- 21190970
TI  - FDA gets new powers to regulate food safety.

PMID- 21190971
TI  - US hospital loses Catholic designation after performing a lifesaving abortion.

PMID- 21190972
TI  - Ineffective surgical procedures are used to treat Canadians with osteoarthritis.

PMID- 21190973
TI  - A high-fat diet elicits differential responses in genes coordinating oxidative
      metabolism in skeletal muscle of lean and obese individuals.
AB  - CONTEXT: In lean individuals, increasing dietary lipid can elicit an increase in
      whole body lipid oxidation; however, with obesity the capacity to respond to
      changes in substrate availability appears to be compromised. OBJECTIVE: To
      determine whether the responses of genes regulating lipid oxidation in skeletal
      muscle differed between lean and insulin resistant obese humans upon exposure to
      a high-fat diet (HFD). DESIGN AND SETTING: A 5-d prospective study conducted in
      the research unit of an academic center. PARTICIPANTS: Healthy, lean (n = 12;
      body mass index = 22.1 +/- 0.6 kg/m(2)), and obese (n=10; body mass index = 39.6
      +/- 1.7 kg/m(2)) males and females, between ages 18 and 30. INTERVENTION:
      Participants were studied before and after a 5-d HFD (65% fat). MAIN OUTCOME
      MEASURES: Skeletal muscle biopsies (vastus lateralis) were obtained in the fasted
      and fed states before and after the HFD and mRNA content for genes involved with
      lipid oxidation determined. Skeletal muscle acylcarnitine content was determined
      in the fed states before and after the HFD. RESULTS: Peroxisome proliferator
      activated receptor (PPAR) alpha mRNA content increased in lean, but not obese,
      subjects after a single high-fat meal. From Pre- to Post-HFD, mRNA content
      exhibited a body size * HFD interaction, where the lean individuals increased
      while the obese individuals decreased mRNA content for pyruvate dehydrogenase
      kinase 4, uncoupling protein 3, PPARalpha, and PPARgamma coactivator-1alpha (P <=
      0.05). In the obese subjects medium-chain acylcarnitine species tended to
      accumulate, whereas no change or a reduction was evident in the lean individuals.
      CONCLUSIONS: These findings indicate a differential response to a lipid stimulus
      in the skeletal muscle of lean and insulin resistant obese humans.

PMID- 21190974
TI  - High rate of persistent hypothyroidism in a large-scale prospective study of
      postpartum thyroiditis in southern Italy.
AB  - CONTEXT: The incidence of postpartum thyroiditis (PPT) varies widely in the
      literature. Limited data exist concerning the hormonal status of women with PPT
      at the end of the first postpartum year. OBJECTIVE: Our aim was to conduct a
      large prospective study of the incidence and clinical course of PPT. DESIGN: A
      total of 4394 women were screened for thyroid function and thyroid autoantibodies
      at 6 and 12 months postpartum. Women were classified as being at high or low risk
      of having thyroid disease before any thyroid testing. SETTING: The study was
      conducted at two ambulatory clinics in southern Italy, an area of mild iodine
      deficiency. PATIENTS: A total of 4394 pregnant women were studied. INTERVENTION:
      There was no intervention. MAIN OUTCOME MEASURES: We measured incidence, clinical
      presentation, and course of postpartum thyroiditis. RESULTS: The incidence of
      postpartum thyroiditis was 3.9% (169 of 4384). Women classified as being at high
      risk for thyroid disease had a higher incidence of PPT than women classified as
      low risk (11.1 vs. 1.9%; odds ratio, 6.69; 95% confidence interval, 4.63, 9.68).
      Eighty-two percent of the 169 women with PPT had a hypothyroid phase during the
      first postpartum year. At the end of the first postpartum year, 54% of the 169
      women had persistent hypothyroidism. CONCLUSIONS: One of every 25 women in
      southern Italy developed PPT. Women at high risk for thyroid disease have an
      increased rate of PPT. The high rate of permanent hypothyroidism at 1 yr should
      result in a reevaluation of the widely held belief that most women with PPT are
      euthyroid at the end of the first postpartum year.

PMID- 21190975
TI  - Clinical risk factors for malignancy and overall survival in patients with
      pheochromocytomas and sympathetic paragangliomas: primary tumor size and primary
      tumor location as prognostic indicators.
AB  - CONTEXT: Pheochromocytomas and sympathetic paragangliomas are rare neuroendocrine
      tumors for which no precise histological or molecular markers have been
      identified to differentiate benign from malignant tumors. OBJECTIVE: The aim was
      to determine whether primary tumor location and size are associated with
      malignancy and decreased survival. DESIGN AND SETTING: We performed a
      retrospective chart review of patients with either pheochromocytoma or
      sympathetic paraganglioma. PATIENTS: The study group comprised 371 patients. MAIN
      OUTCOME MEASURES: Overall survival and disease-specific survival were analyzed
      according to tumor size and location. RESULTS: Sixty percent of patients with
      sympathetic paragangliomas and 25% of patients with pheochromocytomas had
      metastatic disease. Metastasis was more commonly associated with primary tumors
      located in the mediastinum (69%) and the infradiaphragmatic paraaortic area,
      including the organ of Zuckerkandl (66%). The primary tumor was larger in
      patients with metastases than in patients without metastatic disease (P <
      0.0001). Patients with sympathetic paragangliomas had a shorter overall survival
      than patients with pheochromocytomas (P < 0.0001); increased tumor size was
      associated with shorter overall survival (P < 0.001). Patients with sympathetic
      paragangliomas were twice as likely to die of disease than patients with
      pheochromocytomas (hazard ratio = 1.93; 95% confidence interval = 1.20-3.12; P =
      0.007). As per multivariate analysis, the location of the primary tumor was a
      stronger predictor of metastases than was the size of the primary tumor.
      CONCLUSIONS: The size and location of the primary tumor were significant clinical
      risk factors for metastasis and decreased overall survival duration. These
      findings delineate the follow-up and treatment for these tumors.

PMID- 21190976
TI  - Modeling human endometrial decidualization from the interaction between proteome
      and secretome.
AB  - CONTEXT: Decidualization of the human endometrium, which involves morphological
      and biochemical modifications of the endometrial stromal cells (ESCs), is a
      prerequisite for adequate trophoblast invasion and placenta formation. OBJECTIVE:
      This study aims to investigate the proteome and secretome of in vitro
      decidualized ESCs. These data were combined with published genomic information
      and integrated to model the human decidualization interactome. DESIGN:
      Prospective experimental case-control study. SETTING: A private research
      foundation. PATIENTS: Sixteen healthy volunteer ovum donors. INTERVENTION:
      Endometrial samples were obtained, and ESCs were isolated and decidualized in
      vitro. MAIN OUTCOME MEASURES: Two-dimensional difference in-gel electrophoresis,
      matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry,
      Western blot, human protein cytokine array, ELISA, and bioinformatics analysis
      were performed. RESULTS: The proteomic analysis revealed 60 differentially
      expressed proteins (36 over- and 24 underexpressed) in decidualized versus
      control ESCs, including known decidualization markers (cathepsin B) and new
      biomarkers (transglutaminase 2, peroxiredoxin 4, and the ACTB protein). In the
      secretomic analysis, a total of 13 secreted proteins (11 up- and 2 down
      regulated) were identified, including well-recognized markers (IGF binding
      protein-1 and prolactin) and novel ones (myeloid progenitor inhibitory factor-1
      and platelet endothelial cell adhesion molecule-1). These proteome/secretome
      profiles have been integrated into a decidualization interactome model.
      CONCLUSIONS: Proteomic and secretomic have been used as hypothesis-free
      approaches together with complex bioinformatics to model the human decidual
      interactome for the first time. We confirm previous knowledge, describe new
      molecules, and we have built up a model for human in vitro decidualization as
      invaluable tool for the diagnosis, therapy, and interpretation of biological
      phenomena.

PMID- 21190977
TI  - Metformin treatment exerts antiinvasive and antimetastatic effects in human
      endometrial carcinoma cells.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in
      women associated with an increased risk of endometrial hyperplasia. We sought to
      study the effects of metformin treatment (widely used in the management of PCOS
      women) on human endometrial adenocarcinoma cells. OBJECTIVES: To study the
      effects of metformin treatment on in vitro invasion and metastasis in human
      endometrial adenocarcinoma cells. Also, given the link between inflammation with
      endometrial cancer invasion and metastasis, we explored the roles of nuclear
      factor-kappaB (NF-kappaB), matrix metalloproteinases (MMPs) as well as v-akt
      murine thymoma viral oncogene homolog 1 (Akt) and extracellular signal-regulated
      kinases (Erk(1/2)) signaling pathways. DESIGN: Sera were obtained from PCOS and
      control subjects. In vitro invasion were assessed in human endometrial cells (ECC
      1 cells) by wound-healing motility and migration assays. NF-kappaB was studied by
      stably transfecting ECC-1 cells with a cis-reporter plasmid containing luciferase
      reporter gene linked to five repeats of NF-kappaB binding sites. The
      gelatinolytic activities of secreted MMP-2/9 in conditioned media were measured
      by gelatin zymography. Akt and Erk(1/2) phosphorylation were assessed by Western
      blotting. RESULTS: In vitro invasion in ECC-1 cells was significantly attenuated
      by sera from PCOS women after 6 months of metformin treatment (850 mg twice
      daily) compared to matched controls (P < 0.01). These effects appear to be
      associated with NF-kappaB, MMP-2/9, as well as Akt and Erk(1/2) pathways that are
      known to be important regulators of inflammation, tumor invasion and metastasis.
      CONCLUSIONS: Metformin, potentially, may serve as adjuvant treatment in the
      management of patients with endometrial cancer.

PMID- 21190978
TI  - Mitogen-inducible gene-6 is a multifunctional adaptor protein with tumor
      suppressor-like activity in papillary thyroid cancer.
AB  - CONTEXT: Low tumoral expression of mitogen-inducible gene-6 (Mig-6) is associated
      with papillary thyroid cancer (PTC) recurrence after thyroidectomy. OBJECTIVE: We
      hypothesize that Mig-6 behaves as a tumor suppressor in PTC. DESIGN: Mig-6
      expression and promoter methylation status were compared in 31 PTC specimens with
      matched normal thyroid tissue from the same patient. The impact of Mig-6 loss and
      gain of function on nuclear factor kappa-light-chain-enhancer of activated B
      cells (NF-kappaB) activation, global tyrosine kinase phosphorylation, and
      cellular invasion was determined in vitro. RESULTS: Mig-6 protein was abundant in
      all normal thyroid specimens, whereas 77% of PTC had low Mig-6 expression. Mig-6
      promoter methylation was found in 79% of PTC with low Mig-6 expression. Low Mig-6
      expression in PTC specimens was associated with low NF-kappaB activity but high
      levels of epidermal growth factor receptor (EGFR) and ERK phosphorylation. Mig-6
      expression inversely correlated with PTC size but had no association with other
      clinicopathological variables including age, extrathyroidal extension,
      lymphovascular invasion, or histological subtype. Mig-6 knockdown in thyroid
      cancer cell lines resulted in EGFR phosphorylation and diminished NF-kappaB
      activity, whereas Mig-6 overexpression had the opposite effects. Mig-6 knockdown
      activated ErbB2, Met, and Src phosphorylation. Furthermore, Mig-6 regulated ERK
      phosphorylation independent from its effects on EGFR. Mig-6 knockdown promoted
      cellular proliferation, as determined by clonogenic survival. Lastly, Mig-6
      knockdown increased matrix metalloproteinase-2 and -9 activities and increased
      cellular invasion. CONCLUSIONS: Mig-6 has tumor suppressor-like activity in PTC.
      In vivo studies are required to confirm that Mig-6 is a putative tumor suppressor
      in PTC, and future studies should investigate the utility of Mig-6 as a
      diagnostic marker.

PMID- 21190979
TI  - WITHDRAWN: Bone Morphogenetic Protein 15 (BMP15)/Growth Differentiating Factor 9
      Heterodimer Is More Potent than BMP15 Alone in in Vitro Activation of Human
      Primordial Follicles.
AB  - This manuscript was withdrawn at the request of the authors.

PMID- 21190980
TI  - Sonographic measurement of mesenteric fat predicts presence of fatty liver among
      subjects with polycystic ovary syndrome.
AB  - OBJECTIVE: Visceral fat is believed to be important in the pathogenesis of
      metabolic syndrome and fatty liver. In this study, we examined the relationship
      between mesenteric fat thickness and other sonographic indices of adiposity and
      the presence of fatty liver among subjects with polycystic ovary syndrome (PCOS).
      SUBJECTS AND METHODS: A total of 117 Chinese subjects with PCOS were evaluated
      (mean age, 28.6 +/- 6.5 yr; mean body mass index, 24.3 +/- 5.3 kg/m(2)).
      Anthropometric measurements and metabolic risk profile, including a standard oral
      glucose tolerance test, were assessed in all subjects. All subjects underwent an
      ultrasound examination for measurement of thickness of mesenteric, preperitoneal,
      and sc fat as well as evaluation for fatty liver. RESULTS: Forty-six (39.3%) of
      the subjects had fatty liver. PCOS subjects with fatty liver had higher body mass
      index, waist circumference, waist-hip ratio, and systolic blood pressure; a more
      unfavorable lipid profile with higher triglyceride; lower high-density
      lipoprotein cholesterol; higher fasting glucose and insulin; higher 2-h glucose
      during oral glucose tolerance test; lower SHBG; and higher alanine
      aminotransferase. Subjects with fatty liver had increased thickness of
      preperitoneal, mesenteric, and sc fat, as well as increased carotid intima-media
      thickness. Abdominal fat thickness showed moderate correlation to alanine
      aminotransferase as well as fasting insulin. On multivariate logistic regression,
      fasting insulin and mesenteric fat thickness were identified as independent
      predictors of fatty liver among subjects with PCOS. CONCLUSION: Fatty liver is
      present in a significant proportion of Chinese patients with PCOS. Sonographic
      measurement of mesenteric fat is an independent determinant of fatty liver among
      subjects with PCOS and identifies subjects at increased cardiovascular risk.

PMID- 21190981
TI  - Pubertal presentation in seven patients with congenital adrenal hyperplasia due
      to P450 oxidoreductase deficiency.
AB  - CONTEXT: P450 oxidoreductase (POR) is a crucial electron donor to all microsomal
      P450 cytochrome (CYP) enzymes including 17alpha-hydroxylase (CYP17A1), 21
      hydroxylase (CYP21A2) and P450 aromatase. Mutant POR causes congenital adrenal
      hyperplasia with combined glucocorticoid and sex steroid deficiency. P450
      oxidoreductase deficiency (ORD) commonly presents neonatally, with disordered sex
      development in both sexes, skeletal malformations, and glucocorticoid deficiency.
      OBJECTIVE: The aim of the study was to describe the clinical and biochemical
      characteristics of ORD during puberty. DESIGN: Clinical, biochemical, and genetic
      assessment of seven ORD patients (five females, two males) presenting during
      puberty was conducted. RESULTS: Predominant findings in females were incomplete
      pubertal development (four of five) and large ovarian cysts (five of five) prone
      to spontaneous rupture, in some only resolving after combined treatment with
      estrogen/progestin, GnRH superagonists, and glucocorticoids. Pubertal development
      in the two boys was more mildly affected, with some spontaneous progression.
      Urinary steroid profiling revealed combined CYP17A1 and CYP21A2 deficiencies
      indicative of ORD in all patients; all but one failed to mount an appropriate
      cortisol response to ACTH stimulation indicative of adrenal insufficiency.
      Diagnosis of ORD was confirmed by direct sequencing, demonstrating disease
      causing POR mutations. CONCLUSION: Delayed and disordered puberty can be the
      first sign leading to a diagnosis of ORD. Appropriate testosterone production
      during puberty in affected boys but manifest primary hypogonadism in girls with
      ORD may indicate that testicular steroidogenesis is less dependent on POR than
      adrenal and ovarian steroidogenesis. Ovarian cysts in pubertal girls may be
      driven not only by high gonadotropins but possibly also by impaired CYP51A1
      mediated production of meiosis-activating sterols due to mutant POR.

PMID- 21190982
TI  - Prognostic factors of disease-free survival after thyroidectomy in 170 young
      patients with a RET germline mutation: a multicenter study of the Groupe Francais
      d'Etude des Tumeurs Endocrines.
AB  - BACKGROUND: In hereditary medullary thyroid carcinoma (HMTC), prophylactic
      surgery is the only curative option, which should be properly defined both in
      time and extent. OBJECTIVES: To identify and characterize prognostic factors
      associated with disease-free survival (DFS) in children from HMTC families.
      DESIGN: We conducted a retrospective analysis of a multi-center cohort of 170
      patients below age 21 at surgery. Demographic, clinical, genetic, biological data
      [basal and pentagastrine-stimulated calcitonin (CT and CT/Pg, respectively)], and
      tumor node metastasis (TNM) status were collected. DFS was assessed based on
      basal CT levels. Kaplan-Meier curves, Cox regression, and logistic regression
      models were used to determine factors associated with DFS and TNM staging.
      RESULTS: No patients with a preoperative basal CT <31 ng/ml had persistent or
      recurrent disease. Medullary thyroid carcinoma defined by a diameter >=10 mm
      [hazard ratio (HR): 6.0; 95% confidence interval (95% CI): 1.8-19.8] and N1
      status (HR: 20.8; 95% CI: 3.9-109.8) were independently associated with DFS.
      Class D genotype [odds ratio (OR): 48.5, 95% CI: 10.6-225.1], preoperative basal
      CT >30 ng/liter (OR: 43.4, 95% CI: 5.2-359.8), and age >10 (OR: 5.5, 95% CI: 1.4
      21.8) were associated with medullary thyroid carcinoma >=10 mm. No patient with a
      preoperative basal CT <31 ng/ml had a N1 status. Class D genotype (OR: 48.6, 95%
      CI: 8.6-274.1), and age >10 (OR: 4.6, 95% CI: 1.1-19.0) were associated with N1
      status. CONCLUSION: In HMTC patients, DFS is best predicted by TNM staging and
      preoperative basal CT level below 30 pg/ml. Basal CT, class D genotype, and age
      constitute key determinants to decide preoperatively timely surgery.

PMID- 21190983
TI  - The dilemma of how to manage Graves' hyperthyroidism in patients with associated
      orbitopathy.
AB  - CONTEXT: Graves' orbitopathy (GO) is present in about 50% of patients with
      Graves' hyperthyroidism. It may range from mild to moderately severe and (rarely)
      to sight-threatening. Whether antithyroid drugs (ATDs), radioactive iodine (RAI),
      or thyroidectomy should be the treatment of choice in the presence of overt and
      active GO is a matter of debate. EVIDENCE ACQUISITION: The major source of data
      acquisition included PubMed search strategies. Articles published in the last 30
      yr were screened. Furthermore, the bibliographies of relevant citations and
      chapters of major textbooks were evaluated for any additional appropriate
      citation. EVIDENCE SYNTHESIS: Prompt restoration and stable maintenance of
      euthyroidism is important for the course of GO. ATDs and thyroidectomy per se do
      not influence the natural history of GO. RAI can cause progression or de novo
      development of GO, particularly in smokers. This effect can be prevented by oral
      steroid prophylaxis. In patients with mild orbitopathy, the choice of thyroid
      treatment is largely independent of GO. Moderate-to-severe and active GO should
      be treated without delay. Whether in these patients, concomitant treatment of
      hyperthyroidism should be conservative (ATDs) or ablative (RAI, thyroidectomy, or
      both) is presently based on expert opinion rather than evidence. Emerging and
      potentially interesting biological agents, such as rituximab, counteracting
      pathogenic mechanisms of both hyperthyroidism and GO, need to be evaluated in
      randomized clinical trials. CONCLUSIONS: The choice of the optimal treatment for
      hyperthyroidism in patients with moderate-to-severe and active GO remains
      unsettled and is mainly based on personal experience. Randomized clinical trials
      in this field are eagerly needed.

PMID- 21190984
TI  - Vitamin D insufficiency in Korea--a greater threat to younger generation: the
      Korea National Health and Nutrition Examination Survey (KNHANES) 2008.
AB  - CONTEXT: Vitamin D status in the Korean population has not been adequately
      determined. OBJECTIVE: To investigate the vitamin D status and the prevalence of
      vitamin D insufficiency in the Korean population, and also identify the
      predictors for vitamin D insufficiency in Korea. DESIGN AND SETTING: The Fourth
      Korea National Health and Nutrition Examination Surveys (KNHANES IV) in the
      Korean population conducted in 2008. PARTICIPANTS: 3,047 males and 3,878 females
      aged 10 years and older selected in all the 16 administrative districts of South
      Korea. MAIN OUTCOME MEASURES: Serum 25-hydroxyvitamin D [25(OH)D] levels and the
      prevalence of vitamin D insufficiency defined as serum 25(OH)D level of less than
      20 ng/ml. RESULTS: Vitamin D insufficiency was found in 47.3% of males and 64.5%
      of females, whereas only 13.2% of male and 6.7% of female population had a serum
      25(OH)D level of greater than 30 ng/ml. Vitamin D insufficiency was most
      prevalent in the age of 20-29, with a rate of 65.0% in males and 79.9% in
      females, and least prevalent in the age of 60-69 in males and 50-59 in females.
      Those who work usually indoors were more predisposed to vitamin D insufficiency.
      In the adult population, predictors for vitamin D insufficiency included young
      age groups, spring and winter seasons, living in an urban area, and indoor
      occupations. CONCLUSIONS: Vitamin D insufficiency is very common, and it is now a
      greater threat to the younger generation in Korea. Current recommendations for
      vitamin D intakes for Koreans are inadequate, especially for the youth.

PMID- 21190985
TI  - Lorcaserin, a 5-HT(2C) receptor agonist, reduces body weight by decreasing energy
      intake without influencing energy expenditure.
AB  - CONTEXT: Lorcaserin, a selective 5-hydroxytryptamine (5-HT)(2C) receptor agonist,
      reduces body weight. It is unclear whether weight loss is due to reduced energy
      intake (EI) or also to enhanced energy expenditure (EE). OBJECTIVE: This study
      tested the effect of lorcaserin on EI and EE. DESIGN, PARTICIPANTS, AND
      INTERVENTION: In a double-blind, randomized, placebo-controlled trial, 57 (39
      women) overweight and obese (body mass index, 27-45 kg/m(2)) adults were
      randomized to placebo (n = 28) or 10 mg twice daily lorcaserin (n = 29) for 56 d.
      Weight maintenance was imposed during d 1-7. Beginning on d 8, participants
      followed a diet and exercise plan targeting a 600 kcal/d deficit. OUTCOMES: At
      baseline and after 7 and 56 d of treatment, we measured body weight, body
      composition (dual x-ray absorptiometry), blood pressure, heart rate, EI at lunch
      and dinner, subjective appetite ratings, and 24-h EE and 24-h-respiratory
      quotient (RQ), measured by indirect calorimetry in a respiratory chamber.
      RESULTS: After 7 d of weight maintenance, EI was significantly (P < 0.01) reduced
      with lorcaserin but not placebo (mean +/- sem for lorcaserin, -286 +/- 86 kcal;
      placebo, -147 +/- 89 kcal). After 56 d, lorcaserin resulted in significantly
      larger reductions in body weight (lorcaserin, -3.8 +/- 0.4 kg; placebo, -2.2 +/-
      0.5 kg; P < 0.01), EI (lorcaserin, -470 +/- 87 kcal; placebo, -205 +/- 91 kcal; P
      < .05), and appetite ratings than in placebo. Changes in 24-h EE and 24-h RQ did
      not differ between groups, even after 24-h EE was adjusted for body weight and
      composition. Compared with placebo, lorcaserin had no effect on systolic or
      diastolic blood pressure or heart rate after 56 d. CONCLUSIONS: Lorcaserin
      reduces body weight through reduced EI, not altered EE or RQ.

PMID- 21190986
TI  - Antibiotic exposure by 6 months and asthma and allergy at 6 years: Findings in a
      cohort of 1,401 US children.
AB  - Many studies have reported that antibiotic use may be associated with increased
      risk of childhood asthma. Respiratory tract infections in small children may be
      difficult to distinguish from early symptoms of asthma, and studies may have been
      confounded by "protopathic" bias, where antibiotics are used to treat early
      symptoms of asthma. These analyses of a cohort including 1,401 US children assess
      the association between antibiotic use within the first 6 months of life and
      asthma and allergy at 6 years of age between 2003 and 2007. Antibiotic exposure
      was associated with increased risk of asthma (adjusted odds ratio = 1.52, 95%
      confidence interval (CI): 1.07, 2.16). The odds ratio if asthma was first
      diagnosed after 3 years of age was 1.66 (95% CI: 0.99, 2.79) and, in children
      with no history of lower respiratory infection in the first year of life, the
      odds ratio was 1.66 (95% CI: 1.12, 3.46). The adverse effect of antibiotics was
      particularly strong in children with no family history of asthma (odds ratio =
      1.89, 95% CI: 1.00, 3.58) (P(interaction) = 0.03). The odds ratio for a positive
      allergy blood or skin test was 1.59 (95% CI: 1.10, 2.28). The results show that
      early antibiotic use was associated with asthma and allergy at 6 years of age,
      and that protopathic bias was unlikely to account for the main findings.

PMID- 21190987
TI  - Long-term posttraumatic stress symptoms among 3,271 civilian survivors of the
      September 11, 2001, terrorist attacks on the World Trade Center.
AB  - Although the September 11, 2001, terrorist attacks were the largest human-made
      disaster in US history, there is little extant research documenting the attacks'
      consequences among those most directly affected, that is, persons who were in the
      World Trade Center towers. Data from a cross-sectional survey conducted 2-3 years
      after the attacks ascertained the prevalence of long-term, disaster-related
      posttraumatic stress symptoms and probable posttraumatic stress disorder (PTSD)
      in 3,271 civilians who evacuated World Trade Center towers 1 and 2. Overall,
      95.6% of survivors reported at least 1 current posttraumatic stress symptom. The
      authors estimated the probable rate of PTSD at 15.0% by using the PTSD Checklist.
      Women and minorities were at an increased risk of PTSD. A strong inverse relation
      with annual income was observed. Five characteristics of direct exposure to the
      terrorist attacks independently predicted PTSD: being on a high floor in the
      towers, initiating evacuation late, being caught in the dust cloud that resulted
      from the tower collapses, personally witnessing horror, and sustaining an injury.
      Working for an employer that sustained fatalities also increased risk. Each
      addition of an experience of direct exposure resulted in a 2-fold increase in the
      risk of PTSD (odds ratio = 2.09, 95% confidence interval: 1.84, 2.36).
      Identification of these risk factors may be useful when screening survivors of
      large-scale terrorist events for long-term psychological sequelae.

PMID- 21190988
TI  - Evidence from Chile that arsenic in drinking water may increase mortality from
      pulmonary tuberculosis.
AB  - Arsenic in drinking water causes increased mortality from several cancers,
      ischemic heart disease, bronchiectasis, and other diseases. This paper presents
      the first evidence relating arsenic exposure to pulmonary tuberculosis, by
      estimating mortality rate ratios for Region II of Chile compared with Region V
      for the years 1958-2000. The authors compared mortality rate ratios with time
      patterns of arsenic exposure, which increased abruptly in 1958 in Region II and
      then declined starting in 1971. Tuberculosis mortality rate ratios in men started
      increasing in 1968, 10 years after high arsenic exposure commenced. The peak male
      5-year mortality rate ratio occurred during 1982-1986 (rate ratio = 2.1, 95%
      confidence interval: 1.7, 2.6; P < 0.001) and subsequently declined. Mortality
      rates in women were also elevated but with fewer excess pulmonary tuberculosis
      deaths (359 among men and 95 among women). The clear rise and fall of
      tuberculosis mortality rate ratios in men following high arsenic exposure are
      consistent with a causal relation. The findings are biologically plausible in
      view of evidence that arsenic is an immunosuppressant and also a cause of chronic
      lung disease. Finding weaker associations in women is unsurprising, because this
      is true of most arsenic-caused health effects. Confirmatory evidence is needed
      from other arsenic-exposed populations.

PMID- 21190989
TI  - CD8&alpha;+ plasmacytoid precursor DCs induce antigen-specific regulatory T cells
      that enhance HSC engraftment in vivo.
AB  - CD8-positive/T-cell receptor-negative (CD8(+)/TCR(-)) graft facilitating cells
      (FCs) are a novel cell population in bone marrow that potently enhance
      engraftment of hemopoietic stem cells (HSCs). Previously, we showed that the
      CD11c(+)/B220(+)/CD11b(-) plasmacytoid-precursor dendritic cell (p-preDC) FC
      subpopulation plays a critical but nonredundant role in facilitation. In the
      present study, we investigated the mechanism of FC function. We report that FCs
      induce antigen-specific CD4(+)/CD25(+)/FoxP3(+) regulatory T cells (Tregs) in
      vivo. The majority of chimeric Tregs were recipient derived. Chimeric Tregs
      harvested at >= 4 weeks after transplantation significantly enhanced engraftment
      of donor- and recipient-derived HSCs, but not third-party HSCs, in conditioned
      secondary recipients, demonstrating antigen specificity. Although Tregs were
      present 2 and 3 weeks after transplantation, they did not enhance engraftment. In
      contrast, week 5 and greater Tregs potently enhanced engraftment. The function of
      chimeric Tregs was directly correlated with the development of FoxP3 expression.
      Chimeric Tregs also induced significantly stronger suppression of T-cell
      proliferation to donor antigen in vitro. Removal of p-preDC FCs resulted in
      impaired engraftment of allogeneic HSCs and failure to produce chimeric Tregs,
      suggesting that the CD8alpha(+) p-preDC subpopulation is critical in the
      mechanism of facilitation. These data suggest that FCs induce the production of
      antigen-specific Tregs in vivo, which potently enhance engraftment of allogeneic
      HSCs. FCs hold clinical potential because of their ability to remain tolerogenic
      in vivo.

PMID- 21190990
TI  - Dentin matrix protein 1 induces membrane expression of VE-cadherin on endothelial
      cells and inhibits VEGF-induced angiogenesis by blocking VEGFR-2 phosphorylation.
AB  - Dentin matrix protein 1 (DMP1) is a member of the small integrin-binding ligand N
      linked glycoprotein (SIBLING) family, a group of proteins initially described as
      mineralized extracellular matrices components. More recently, SIBLINGs have been
      implicated in several key steps of cancer progression, including angiogenesis.
      Although proangiogenic activities have been demonstrated for 2 SIBLINGs, the role
      of DMP1 in angiogenesis has not yet been addressed. We demonstrate that this
      extracellular matrix protein induced the expression of vascular endothelial
      cadherin (VE-cadherin), a key regulator of intercellular junctions and contact
      inhibition of growth of endothelial cells that is also known to modulate vascular
      endothelial growth factor receptor 2 (VEGFR-2) activity, the major high-affinity
      receptor for VEGF. DMP1 induced VE-cadherin and p27(Kip1) expression followed by
      cell-cycle arrest in human umbilical vein endothelial cells (HUVECs) in a CD44
      dependent manner. VEGF-induced proliferation, migration, and tubulogenesis
      responses were specifically blocked on DMP1 pretreatment of HUVECs. Indeed, after
      VE-cadherin induction, DMP1 inhibited VEGFR-2 phosphorylation and Src-mediated
      signaling. However, DMP1 did not interfere with basic fibroblast growth factor
      induced angiogenesis. In vivo, DMP1 significantly reduced laser-induced choroidal
      neovascularization lesions and tumor-associated angiogenesis. These data enable
      us to put DMP1 on the angiogenic chessboard for the first time and to identify
      this protein as a new specific inhibitor of VEGF-induced angiogenesis.

PMID- 21190991
TI  - How I treat LGL leukemia.
AB  - Large granular lymphocyte (LGL) leukemia is characterized by a clonal expansion
      of either CD3(+) cytotoxic T or CD3(-) NK cells. Prominent clinical features of T
      LGL leukemia include neutropenia, anemia and rheumatoid arthritis (RA). The
      terminal effector memory phenotype (CD3(+)/CD45RA(+)/CD62L(-)CD57(+)) of T-LGL
      suggests a pivotal chronic antigen-driven immune response. LGL survival is then
      promoted by platelet-derived growth factor and interleukin-15, resulting in
      global dysregulation of apoptosis and resistance to normal pathways of activation
      induced cell death. These pathogenic features explain why treatment of T-LGL
      leukemia is based on immunosuppressive therapy. The majority of these patients
      eventually need treatment because of severe or symptomatic neutropenia, anemia,
      or RA. No standard therapy has been established because of the absence of large
      prospective trials. The authors use low-dose methotrexate initially for T-LGL
      leukemia patients with neutropenia and/or RA. We recommend either methotrexate or
      oral cyclophosphamide as initial therapy for anemia. If treatment is not
      successful, patients are switched to either the other agent or cyclosporine. The
      majority of patients experience an indolent clinical course. Deaths infrequently
      occur because of infections related to severe neutropenia. As there are no
      curative therapeutic modalities for T-LGL leukemia, new treatment options are
      needed.

PMID- 21190992
TI  - Rara haploinsufficiency modestly influences the phenotype of acute promyelocytic
      leukemia in mice.
AB  - RARA (retinoic acid receptor alpha) haploinsufficiency is an invariable
      consequence of t(15;17)(q22;q21) translocations in acute promyelocytic leukemia
      (APL). Retinoids and RARA activity have been implicated in hematopoietic self
      renewal and neutrophil maturation. We and others therefore predicted that RARA
      haploinsufficiency would contribute to APL pathogenesis. To test this hypothesis,
      we crossed Rara(+/-) mice with mice expressing PML (promyelocytic leukemia)-RARA
      from the cathepsin G locus (mCG-PR). We found that Rara haploinsufficiency
      cooperated with PML-RARA, but only modestly influenced the preleukemic and
      leukemic phenotype. Bone marrow from mCG-PR(+/-) * Rara(+/-) mice had decreased
      numbers of mature myeloid cells, increased ex vivo myeloid cell proliferation,
      and increased competitive advantage after transplantation. Rara
      haploinsufficiency did not alter mCG-PR-dependent leukemic latency or penetrance,
      but did influence the distribution of leukemic cells; leukemia in mCG-PR(+/-) *
      Rara(+/-) mice presented more commonly with low to normal white blood cell counts
      and with myeloid infiltration of lymph nodes. APL cells from these mice were
      responsive to all-trans retinoic acid and had virtually no differences in
      expression profiling compared with tumors arising in mCG-PR(+/-) * Rara(+/+)
      mice. These data show that Rara haploinsufficiency (like Pml haploinsufficiency
      and RARA-PML) can cooperate with PML-RARA to influence the pathogenesis of APL in
      mice, but that PML-RARA is the t(15;17) disease-initiating mutation.

PMID- 21190993
TI  - Evi-1 is a transcriptional target of mixed-lineage leukemia oncoproteins in
      hematopoietic stem cells.
AB  - Ecotropic viral integration site-1 (Evi-1) is a nuclear transcription factor that
      plays an essential role in the regulation of hematopoietic stem cells. Aberrant
      expression of Evi-1 has been reported in up to 10% of patients with acute myeloid
      leukemia and is a diagnostic marker that predicts a poor outcome. Although
      chromosomal rearrangement involving the Evi-1 gene is one of the major causes of
      Evi-1 activation, overexpression of Evi-1 is detected in a subgroup of acute
      myeloid leukemia patients without any chromosomal abnormalities, which indicates
      the presence of other mechanisms for Evi-1 activation. In this study, we found
      that Evi-1 is frequently up-regulated in bone marrow cells transformed by the
      mixed-lineage leukemia (MLL) chimeric genes MLL-ENL or MLL-AF9. Analysis of the
      Evi-1 gene promoter region revealed that MLL-ENL activates transcription of Evi
      1. MLL-ENL-mediated up-regulation of Evi-1 occurs exclusively in the
      undifferentiated hematopoietic population, in which Evi-1 particularly
      contributes to the propagation of MLL-ENL-immortalized cells. Furthermore, gene
      expression analysis of human acute myeloid leukemia cases demonstrated the stem
      cell-like gene-expression signature of MLL-rearranged leukemia with high levels
      of Evi-1. Our findings indicate that Evi-1 is one of the targets of MLL
      oncoproteins and is selectively activated in hematopoietic stem cell-derived MLL
      leukemic cells.

PMID- 21190994
TI  - An observational study of outcomes after initial infused therapy in Medicare
      patients diagnosed with chronic lymphocytic leukemia.
AB  - The study goal was to characterize older chronic lymphocytic leukemia (CLL)
      patients and to evaluate outcomes in those patients who initiated infused
      therapy. Patients 66 years of age and older in the Surveillance, Epidemiology,
      and End Results (SEER) program with a CLL diagnosis were matched to their
      Medicare Part A and Part B claims for long-term follow-up. Treatment patterns,
      survival after initiation of infused therapy, and both hematologic and
      hospitalization outcomes were assessed. There were 6433 CLL patients identified,
      and 2040 received infused therapy. Treated patients were categorized as receiving
      rituximab monotherapy (16%), rituximab plus chemotherapy (14%), and chemotherapy
      alone (70%) based on the initial 60 days after infusion. Rituximab plus
      chemotherapy compared with chemotherapy alone was associated with a 25% lower
      risk of overall mortality (95% confidence interval, 9%-38%). Restricting to
      patients age 70 years and older did not change the risk reduction for rituximab
      plus chemotherapy. Hematologic interventions were more common with rituximab plus
      chemotherapy compared with chemotherapy alone, but there was no difference in all
      cause hospitalizations. These analyses, based on observational data, suggest that
      the benefits of initial therapy with rituximab in a heterogeneous group of older
      CLL patients are comparable with those demonstrated in younger patients.

PMID- 21190995
TI  - Effects of a partly self-administered exercise program before, during, and after
      allogeneic stem cell transplantation.
AB  - Before, during, and after allogeneic hematopoietic stem cell transplantation
      (allo-HSCT), patients experience considerable physical and psychologic distress.
      Besides graft-versus-host disease and infections, reduced physical performance
      and high levels of fatigue affect patients' quality of life. This multicenter
      randomized controlled trial examined the effects of a partly self-administered
      exercise intervention before, during, and after allo-HSCT on these side effects.
      After randomization to an exercise and a social contact control group 105
      patients trained in a home-based setting before hospital admission, during
      inpatient treatment and a 6- to 8-week period after discharge. Fatigue, physical
      performance, quality of life, and physical/psychologic distress were measured by
      standardized instruments at baseline, admission to, and discharge from hospital
      and 6 to 8 weeks after discharge. The exercise group showed significantly
      improvement in fatigue scores (up to 15% improvement in exercise group vs up to
      28% deterioration in control; P<.01-.03), physical fitness/functioning (P=.02
      .03) and global distress (P=.03). All effects were at least detectable at one
      assessment time point after hospitalization or repeatedly. Physical fitness
      correlated significantly with all reported symptoms/variables. In conclusion,
      this partly supervised exercise intervention is beneficial for patients
      undergoing allo-HSCT. Because of low personnel requirements, it might be valuable
      to integrate such a program into standard medical care.

PMID- 21190996
TI  - A randomized comparison of 4 courses of standard-dose multiagent chemotherapy
      versus 3 courses of high-dose cytarabine alone in postremission therapy for acute
      myeloid leukemia in adults: the JALSG AML201 Study.
AB  - We conducted a prospective randomized study to assess the optimal postremission
      therapy for adult acute myeloid leukemia in patients younger than 65 years in the
      first complete remission. A total of 781 patients in complete remission were
      randomly assigned to receive consolidation chemotherapy of either 3 courses of
      high-dose cytarabine (HiDAC, 2 g/m(2) twice daily for 5 days) alone or 4 courses
      of conventional standard-dose multiagent chemotherapy (CT) established in the
      previous JALSG AML97 study. Five-year disease-free survival was 43% for the HiDAC
      group and 39% for the multiagent CT group (P = .724), and 5-year overall survival
      was 58% and 56%, respectively (P = .954). Among the favorable cytogenetic risk
      group (n = 218), 5-year disease-free survival was 57% for HiDAC and 39% for
      multiagent CT (P = .050), and 5-year overall survival was 75% and 66%,
      respectively (P = .174). In the HiDAC group, the nadir of leukocyte counts was
      lower, and the duration of leukocyte less than 1.0 * 10(9)/L longer, and the
      frequency of documented infections higher. The present study demonstrated that
      the multiagent CT regimen is as effective as our HiDAC regimen for consolidation.
      Our HiDAC regimen resulted in a beneficial effect on disease-free survival only
      in the favorable cytogenetic leukemia group. This trial was registered at
      www.umin.ac.jp/ctr/ as #C000000157.

PMID- 21190997
TI  - Ex vivo maintenance of hematopoietic stem cells by quiescence induction through
      Fbxw7&alpha; overexpression.
AB  - Cell-cycle quiescence in hematopoietic stem cells (HSCs) is essential for
      maintaining stemness by protecting cells from differentiation or senescence. F
      box and WD-40 domain protein 7 (Fbxw7) maintains HSCs and suppresses
      leukemogenesis by mediating ubiquitin-dependent degradation of cell-cycle
      activators and oncoproteins. Fbxw7alpha was shown to be the preferentially
      expressed Fbxw7 isoform in primitive HSCs. Forced Fbxw7alpha expression in
      lineage marker Sca-1(+)c-Kit(+) cells led to cell-cycle dormancy by reducing the
      protein levels of the Fbxw7 substrates c-Myc, Notch1, and phosphorylated S6 (a
      key downstream element of mTOR). Hypoxia, an essential factor for HSC quiescence,
      suppressed c-Myc in an Fbxw7alpha-dependent manner. Fbxw7alpha-overexpressing
      lineage marker Sca-1(+)c-Kit(+) cells sustained high reconstitution capacities
      during in vitro culture. These data suggest that Fbxw7alpha sustains HSC dormancy
      through c-Myc, Notch1, and the mTOR pathways. The modulation of Fbxw7alpha
      expression or activity represents a promising new tool for ex vivo HSC
      maintenance.

PMID- 21190998
TI  - IL-29 and IFNalpha differ in their ability to modulate IL-12 production by TLR
      activated human macrophages and exhibit differential regulation of the IFNgamma
      receptor expression.
AB  - The interferon-lambda (IFNlambda) family of cytokines, consisting of interleukin
      28A (IFNlambda2), IL-28B (IFNlambda3), and IL-29 (IFNlambda1), have been
      extensively studied for their antiviral activities. However, little is known
      about the effect of IFNlambda on antigen-presenting cells. In the present study,
      we show for the first time that IL-29 can increase Toll-like receptor (TLR)
      induced IL-12p40 production by human monocyte-derived macrophages. In contrast,
      IL-29 did not affect monocytes or monocyte-derived dendritic cells (DCs) because
      of restricted IL-28 receptor alpha chain expression by macrophages. Furthermore,
      IL-29-treated macrophages were more responsive to IFNgamma, because IL-29
      enhanced IFNgamma-induced IL-12p40 and tumor necrosis factor (TNF) production by
      macrophages on R848 stimulation. However, IFNalpha suppressed IFNgamma-induced IL
      12p40 and tumor necrosis factor TNF production by human macrophages. The
      differential effects of IL-29 and IFNalpha on the responsiveness of macrophages
      to IFNgamma could not be explained by an effect on TLR7 or TLR8 mRNA expression
      or by altered IL-10 signaling. However, we demonstrated that IL-29 up-regulated,
      whereas IFNalpha down-regulated, the surface expression of the IFNgamma receptor
      1 chain on macrophages, thereby resulting in differential responsiveness of TLR
      challenged macrophages to IFNgamma. Our findings on the differences between
      IFNalpha and IL-29 in modulating TLR-induced cytokine production by macrophages
      may contribute to understanding the role of IFNs in regulating immunity to
      pathogens.

PMID- 21190999
TI  - Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively
      altered PRC2 catalytic activity, to increase H3K27 trimethylation.
AB  - Next-generation sequencing of follicular lymphoma and diffuse-large B-cell
      lymphoma has revealed frequent somatic, heterozygous Y641 mutations in the
      histone methyltransferase EZH2. Heterozygosity and the presence of equal
      quantities of both mutant and wild-type mRNA and expressed protein suggest a
      dominant mode of action. Surprisingly, B-cell lymphoma cell lines and lymphoma
      samples harboring heterozygous EZH2(Y641) mutations have increased levels of
      histone H3 Lys-27-specific trimethylation (H3K27me3). Expression of EZH2(Y641F/N)
      mutants in cells with EZH2(WT) resulted in an increase of H3K27me3 levels in
      vivo. Structural modeling of EZH2(Y641) mutants suggests a "Tyr/Phe switch" model
      whereby structurally neutral, nontyrosine residues at position 641 would decrease
      affinity for unmethylated and monomethylated H3K27 substrates and potentially
      favor trimethylation. We demonstrate, using in vitro enzyme assays of
      reconstituted PRC2 complexes, that Y641 mutations result in a decrease in
      monomethylation and an increase in trimethylation activity of the enzyme relative
      to the wild-type enzyme. This represents the first example of a disease
      associated gain-of-function mutation in a histone methyltransferase, whereby
      somatic EZH2 Y641 mutations in lymphoma act dominantly to increase, rather than
      decrease, histone methylation. The dominant mode of action suggests that allele
      specific EZH2 inhibitors should be a future therapeutic strategy for this
      disease.

PMID- 21191000
TI  - Direct involvement of tumor necrosis factor-&alpha; in the regulation of glucose
      uptake in rainbow trout muscle cells.
AB  - The proinflammatory cytokine TNF-alpha is known to have a direct action on
      skeletal muscle in mammals. However, little is known regarding the potential
      effects of cytokines on nonimmune tissues, particularly in skeletal muscle, in
      fish. The aim of this study was to investigate the effects of recombinant trout
      TNF-alpha (rtTNF-alpha) on skeletal muscle carbohydrate metabolism in rainbow
      trout (Oncorhynchus mykiss). We used a primary cell culture of muscle cells from
      rainbow trout to show that rtTNF-alpha stimulates glucose uptake in myoblasts and
      myotubes at concentrations that do not affect the viability of the cells,
      requiring de novo protein synthesis as shown by the impairment of rtTNF-alpha
      stimulated glucose uptake by cycloheximide. With the use of specific inhibitors,
      we show that rtTNF-alpha-stimulated glucose uptake is mediated by the p38MAPK, NF
      kappaB, and JNK pathways. Additionally, we provide evidence that the stimulatory
      effects of rtTNF-alpha on glucose uptake in trout skeletal muscle cells may be
      caused, at least in part, by an increase in the amount of GLUT4 at the plasma
      membrane. Incubation of trout muscle cells with conditioned medium from LPS
      stimulated trout macrophages, enriched in TNF-alpha, increased glucose uptake.
      Our results indicate that recombinant, as well as native trout TNF-alpha,
      directly stimulates glucose uptake in trout muscle cells and provide evidence,
      for the first time in nonmammalian vertebrates, for a potential regulatory role
      of TNF-alpha in skeletal muscle metabolism.

PMID- 21191001
TI  - Adrenocorticotropic hormone and corticosterone responses to acute hypoxia in the
      neonatal rat: effects of body temperature maintenance.
AB  - The corticosterone response to acute hypoxia in neonatal rats develops in the 1st
      wk of life, with a shift from ACTH independence to ACTH dependence. Acute hypoxia
      also leads to hypothermia, which may be protective. There is little information
      about the endocrine effects of body temperature maintenance during periods of
      neonatal hypoxia. We hypothesized that prevention of hypothermia during neonatal
      hypoxia would augment the adrenocortical stress response. Rat pups separated from
      their dams were studied at postnatal days 2 and 8 (PD2 and PD8). In one group of
      pups, body temperature was allowed to spontaneously decrease during a 30-min
      prehypoxia period. Pups were then exposed to 8% O(2) for 3 h and allowed to
      become spontaneously hypothermic or externally warmed (via servo-controlled heat)
      to maintain isothermia. In another group, external warming was used to maintain
      isothermia during the prehypoxia period, and then hypoxia with or without
      isothermia was applied. Plasma ACTH and corticosterone and mRNA expression of
      genes for upstream proteins involved in the steroidogenic pathway were measured.
      Maintenance of isothermia during the prehypoxia period increased baseline plasma
      ACTH at both ages. Hypothermic hypoxia caused an increase in plasma
      corticosterone; this response was augmented by isothermia at PD2, when the
      response was ACTH-independent, and at PD8, when the response was ACTH-dependent.
      In PD8 rats, isothermia also augmented the plasma ACTH response to hypoxia. We
      conclude that maintenance of isothermia augments the adrenocortical response to
      acute hypoxia in the neonate. Prevention of hypothermia may increase the stress
      response during neonatal hypoxia, becoming more pronounced with increased age.

PMID- 21191002
TI  - Renal programming: cause for concern?
AB  - Development of the kidney can be altered in utero in response to a suboptimal
      environment. The intrarenal factors that have been most well characterized as
      being sensitive to programming events are kidney mass/nephron endowment, the
      renin-angiotensin system, tubular sodium handling, and the renal sympathetic
      nerves. Newborns that have been subjected to an adverse intrauterine environment
      may thus begin life at a distinct disadvantage, in terms of renal function, at a
      time when the kidney must take over the primary role for extracellular fluid
      homeostasis from the placenta. A poor beginning, causing renal programming, has
      been linked to increased risk of hypertension and renal disease in adulthood.
      However, although a cause for concern, increasingly, evidence demonstrates that
      renal programming is not a fait accompli in terms of future cardiovascular and
      renal disease. A greater understanding of postnatal renal maturation and the
      impact of secondary factors (genes, sex, diet, stress, and disease) on this
      process is required to predict which babies are at risk of increased
      cardiovascular and renal disease as adults and to be able to devise preventative
      measures.

PMID- 21191003
TI  - Functional plasticity of mitochondrion-rich cells in the skin of euryhaline
      medaka larvae (Oryzias latipes) subjected to salinity changes.
AB  - A noninvasive technique, the scanning ion-selective electrode technique (SIET)
      was applied to measure Na(+) and Cl(-) transport by the yolk-sac skin and
      individual mitochondrion-rich cells (MRCs) in intact medaka larvae (Oryzias
      latipes). In seawater (SW)-acclimated larvae, significant outward Na(+) and Cl(-)
      gradients were measured at the yolk-sac surface, indicating secretions of Na(+)
      and Cl(-) from the yolk-sac skin. With Na(+) pump immunostaining and microscopic
      observation, two groups of MRCs were identified on the yolk-sac skin of SW
      larvae. These were single MRCs (s-MRCs), which do not have an accompanying
      accessory cell (AC), and multicellular complex MRCs (mc-MRCs), which usually
      consist of an MRC and an accompanying AC. The percentage of mc-MRC was ~60% in 30
      parts per thousand of SW, and it decreased with the decrease of external
      salinity. By serial SIET probing over the surface of the MRCs and adjacent
      keratinocytes (KCs), significant outward fluxes of Na(+) and Cl(-) were detected
      at the apical opening (membrane) of mc-MRCs, whereas only outward Cl(-) flux, but
      not Na(+) flux, was detected at s-MRCs. Treatment with 100 MUM ouabain or
      bumetanide effectively blocked the Na(+) and Cl(-) secretion. Following
      freshwater (FW) to SW transfer, Na(+) and Cl(-) secretions by the yolk-sac skin
      were fully developed in 5 h and 2 h, respectively. In contrast, both Na(+) and
      Cl(-) secretions downregulated rapidly after SW to FW transfer. Sequential
      probing at individual MRCs found that Na(+) and Cl(-) secretions declined
      dramatically after SW to FW transfer and Na(+)/Cl(-) uptake was detected at the
      same s-MRCs and mc-MRCs after 5 h. This study provides evidence demonstrating
      that ACs are required for Na(+) excretion and MRCs possess a functional
      plasticity in changing from a Na(+)/Cl(-)-secreting cell to a Na(+)/Cl(-)
      absorbing cell.

PMID- 21191004
TI  - Reexamining the physical examination for obese patients.

PMID- 21191005
TI  - Vaccine-induced control of viral shedding following rhesus cytomegalovirus
      challenge in rhesus macaques.
AB  - The use of animal models of human cytomegalovirus (HCMV) infection is critical to
      refine HCMV vaccine candidates. Previous reports have demonstrated that
      immunization of rhesus monkeys against rhesus cytomegalovirus (RhCMV) can reduce
      both local and systemic replication of RhCMV following experimental RhCMV
      challenge. These studies used prime/boost combinations of DNA expression plasmids
      alone or DNA priming and boosting with either inactivated virion particles or
      modified vaccinia virus Ankara (MVA) expressing the same antigens. Viral outcomes
      included reduced RhCMV replication at the site of subcutaneous inoculation and
      RhCMV viremia following intravenous inoculation. Since shedding of
      cytomegalovirus from mucosal surfaces is critical for horizontal transmission of
      the virus, DNA priming/MVA boosting was evaluated for the ability to reduce oral
      shedding of RhCMV following subcutaneous challenge. Of six rhesus monkeys
      vaccinated exclusively against RhCMV glycoprotein B (gB), phosphoprotein 65
      (pp65), and immediate-early 1 (IE1), half showed viral loads in saliva that were
      lower than those of control monkeys by 1 to 3 orders of magnitude. Further, there
      was a strong association of memory pp65 T cell responses postchallenge in animals
      exhibiting the greatest reduction in oral shedding. These results highlight the
      fact that a DNA/MVA vaccination regimen can achieve a notable reduction in a
      critical parameter of viral replication postchallenge. The recently completed
      clinical trial of a gB subunit vaccine in which the rate of HCMV infection was
      reduced by 50% in the individuals receiving the vaccine is consistent with the
      results of this study suggesting that additional immunogens are likely essential
      for maximum protection in an outbred human population.

PMID- 21191006
TI  - N-linked glycosylation facilitates sialic acid-independent attachment and entry
      of influenza A viruses into cells expressing DC-SIGN or L-SIGN.
AB  - It is widely recognized that sialic acid (SA) can mediate attachment of influenza
      virus to the cell surface, and yet the specific receptors that mediate virus
      entry are not known. For many viruses, a definitive demonstration of receptor
      function has been achieved when nonpermissive cells are rendered susceptible to
      infection following transfection of the gene encoding a putative receptor. For
      influenza virus, such approaches have been confounded by the abundance of SA on
      mammalian cells so that it has been difficult to identify cell lines that are not
      susceptible to infection. We examined influenza virus infection of Lec2 Chinese
      hamster ovary (CHO) cells, a mutant cell line deficient in SA. Lec2 CHO cells
      were resistant to influenza virus infection, and stable cell lines expressing
      either DC-SIGN or L-SIGN were generated to assess the potential of each molecule
      to function as SA-independent receptors for influenza A viruses. Virus strain
      BJx109 (H3N2) bound to Lec2 CHO cells expressing DC-SIGN or L-SIGN in a Ca(2+)
      dependent manner, and transfected cells were susceptible to virus infection.
      Treatment of Lec2-DC-SIGN and Lec2-L-SIGN cells with mannan, but not bacterial
      neuraminidase, blocked infection, a finding consistent with SA-independent virus
      attachment and entry. Moreover, virus strain PR8 (H1N1) bears low levels of
      mannose-rich glycans and was inefficient at infecting Lec2 CHO cells expressing
      either DC-SIGN or L-SIGN, whereas other glycosylated H1N1 subtype viruses could
      infect cells efficiently. Together, these data indicate that human C-type lectins
      (DC-SIGN and L-SIGN) can mediate attachment and entry of influenza viruses
      independently of cell surface SA.

PMID- 21191007
TI  - Rhesus and human cytomegalovirus glycoprotein L are required for infection and
      cell-to-cell spread of virus but cannot complement each other.
AB  - Rhesus cytomegalovirus (RhCMV), the homolog of human cytomegalovirus (HCMV),
      serves as a model for understanding the pathogenesis of HCMV and for developing
      candidate vaccines. In order to develop a replication-defective virus as a
      vaccine candidate, we constructed RhCMV with glycoprotein L (gL) deleted. RhCMV
      gL was essential for viral replication, and virus with gL deleted could only
      replicate in cells expressing RhCMV gL. Noncomplementing cells infected with
      RhCMV with gL deleted released intact, noninfectious RhCMV particles that were
      indistinguishable from wild-type RhCMV by electron microscopy and could be
      rescued by treatment of cells with polyethylene glycol. In addition,
      noncomplementing cells infected with RhCMV with gL deleted produced levels of gB,
      the major target of neutralizing antibodies, at levels similar to those observed
      in cells infected with wild-type RhCMV. Since RhCMV and HCMV gL share 53% amino
      acid identity, we determined whether the two proteins could complement the
      heterologous virus. Cells transfected with an HCMV bacterial artificial
      chromosome with gL deleted yielded virus that could replicate in human cells
      expressing HCMV gL. This is the second HCMV mutant with an essential glycoprotein
      deleted that has been complemented in cell culture. Finally, we found that HCMV
      gL could not complement the replication of RhCMV with gL deleted and that RhCMV
      gL could not complement the replication of HCMV with gL deleted. These data
      indicate that RhCMV and HCMV gL are both essential for replication of their
      corresponding viruses and, although the two gLs are highly homologous, they are
      unable to complement each another.

PMID- 21191009
TI  - Crystal structure of human antibody 2909 reveals conserved features of quaternary
      structure-specific antibodies that potently neutralize HIV-1.
AB  - Monoclonal antibody 2909 belongs to a class of potently neutralizing antibodies
      that recognize quaternary epitopes on HIV-1. Some members of this class, such as
      2909, are strain specific, while others, such as antibody PG16, are broadly
      neutralizing; all, however, recognize a region on the gp120 envelope glycoprotein
      that includes two loops (V2 and V3) and forms appropriately only in the
      oligomeric HIV-1 spike (gp120(3)/gp41(3)). Here we present the crystal structure
      of 2909 and report structure-function analysis with antibody chimeras composed of
      2909 and other members of this antibody class. The 2909 structure was dominated
      by a heavy-chain third-complementarity-determining region (CDR H3) of 21
      residues, which comprised 36% of the combining surface and formed a beta-hairpin
      club extending ~20 A beyond the rest of the antibody. Sequence analysis and mass
      spectrometry identified sites of tyrosine sulfation at the middle and top of CDR
      H3; substitutions with phenylalanine either ablated (middle substitution) or
      substantially diminished (top substitution) neutralization. Chimeric antibodies
      composed of heavy and light chains, exchanged between 2909 and other members of
      the class, indicated a substantial lack of complementation. Comparison of 2909 to
      PG16 (which is tyrosine sulfated and the only other member of the class for which
      a structure has previously been reported) showed that both utilize protruding,
      anionic CDR H3s for recognition. Thus, despite some diversity, members of this
      class share structural and functional similarities, with conserved features of
      the CDR H3 subdomain likely reflecting prevalent solutions by the human immune
      system for recognition of a quaternary site of HIV-1 vulnerability.

PMID- 21191010
TI  - Retrovirus-induced spongiform neurodegeneration is mediated by unique central
      nervous system viral targeting and expression of env alone.
AB  - Certain murine leukemia viruses (MLVs) can induce progressive noninflammatory
      spongiform neurodegeneration similar to that caused by prions. The primary MLV
      determinants responsible have been mapped to within the env gene; however, it has
      remained unclear how env mediates disease, whether non-Env viral components are
      required, and what central nervous system (CNS) cells constitute the critical CNS
      targets. To address these questions, we examined the effect of transplanting
      engraftable C17.2 neural stem cells engineered to pseudotype, disseminate, and
      trans-complement neurovirulent (CasBrE, CasE, and CasES) or non-neurovirulent
      (Friend and SFF-FE) env sequences (SU or SU/TM) within the CNS using either the
      "non-neurovirulent" amphotropic helper virus, 4070A, or pgag-polgpt (a
      nonpackaged vector encoding Gag-Pol). These studies revealed that acute MLV
      induced spongiosis results from two separable activities of Env. First, Env
      causes neuropathology through unique viral targeting within the CNS, which was
      efficiently mediated by ecotropic Envs (CasBrE and Friend), but not 4070A
      amphotropic Env. Second, Env induces spongiosis through a toxin activity that is
      MLV-receptor independent and does not require the coexpression of other viral
      structural proteins. CasBrE and 4070A Envs possess the toxin activity, whereas
      Friend Env does not. Although the identity of the critical viral target cell(s)
      remains unresolved, our results appear to exclude microglia and oligodendrocyte
      lineage cells, while implicating viral entry into susceptible neurons. Thus, MLV
      induced disease parallels prionopathies in that a single protein, Env, mediates
      both the CNS targeting and the toxicity of the infectious agent that manifests
      itself as progressive vacuolar neurodegeneration.

PMID- 21191008
TI  - Origin and evolution of HIV-1 in breast milk determined by single-genome
      amplification and sequencing.
AB  - HIV transmission via breastfeeding accounts for a considerable proportion of
      infant HIV acquisition. However, the origin and evolution of the virus population
      in breast milk, the likely reservoir of transmitted virus variants, are not well
      characterized. In this study, HIV envelope (env) genes were sequenced from virus
      variants amplified by single-genome amplification from plasmas and milk of 12
      chronically HIV-infected, lactating Malawian women. Maximum likelihood trees and
      statistical tests of compartmentalization revealed interspersion of plasma and
      milk HIV env sequences in the majority of subjects, indicating limited or no
      compartmentalization of milk virus variants. However, phylogenetic tree analysis
      further revealed monotypic virus variants that were significantly more frequent
      in milk (median proportion of identical viruses, 29.5%; range, 0 to 61%) than in
      plasma (median proportion of identical viruses, 0%; range, 0 to 26%) (P = 0.002),
      suggesting local virus replication in the breast milk compartment. Moreover,
      clonally amplified virus env genes in milk produced functional virus Envs that
      were all CCR5 tropic. Milk and plasma virus Envs had similar predicted phenotypes
      and neutralization sensitivities to broadly neutralizing antibodies in both
      transmitting and nontransmitting mothers. Finally, phylogenetic comparison of
      longitudinal milk and plasma virus env sequences revealed synchronous virus
      evolution and new clonal amplification of evolved virus env genes in milk. The
      limited compartmentalization and the clonal amplification of evolving, functional
      viruses in milk indicate continual seeding of the mammary gland by blood virus
      variants, followed by transient local replication of these variants in the breast
      milk compartment.

PMID- 21191011
TI  - Preferential induction of protective T cell responses to Theiler's virus in
      resistant (C57BL/6 x SJL)F1 mice.
AB  - Infection of the central nervous system (CNS) with Theiler's murine
      encephalomyelitis virus (TMEV) induces an immune-mediated demyelinating disease
      in susceptible mouse strains such as SJL/J (H-2(s)) but not in strains such as
      C57BL/6 (H-2(b)). In addition, it has been shown that (C57BL/6 * SJL/J)F1 mice
      (F1 mice), which carry both resistant and susceptible MHC haplotypes (H-2(b/s)),
      are resistant to both viral persistence and TMEV-induced demyelinating disease.
      In this study, we further analyzed the immune responses underlying the resistance
      of F1 mice. Our study shows that the resistance of F1 mice is associated with a
      higher level of the initial virus-specific H-2(b)-restricted CD8(+) T cell
      responses than of the H-2(s)-restricted CD8(+) T cell responses. In contrast,
      pathogenic Th17 responses to viral epitopes are lower in F1 mice than in
      susceptible SJL/J mice. Dominant effects of resistant genes expressed in antigen
      presenting cells of F1 mice on regulation of viral replication and induction of
      protective T cell responses appear to play a crucial role in disease resistance.
      Although the F1 mice are resistant to disease, the level of viral RNA in the CNS
      was intermediate between those of SJL/J and C57BL/6 mice, indicating the presence
      of a threshold of viral expression for pathogenesis.

PMID- 21191012
TI  - The Vaccinia virus complement control protein modulates adaptive immune responses
      during infection.
AB  - Complement activation is an important component of the innate immune response
      against viral infection and also shapes adaptive immune responses. Despite
      compelling evidence that complement activation enhances T cell and antibody (Ab)
      responses during viral infection, it is unknown whether inhibition of complement
      by pathogens alters these responses. Vaccinia virus (VACV) modulates complement
      activation by encoding a complement regulatory protein called the vaccinia virus
      complement control protein (VCP). Although VCP has been described as a virulence
      factor, the mechanisms by which VCP enhances VACV pathogenesis have not been
      fully defined. Since complement is necessary for optimal adaptive immune
      responses to several viruses, we hypothesized that VCP contributes to
      pathogenesis by modulating anti-VACV T cell and Ab responses. In this study, we
      used an intradermal model of VACV infection to compare pathogenesis of wild-type
      virus (vv-VCPwt) and a virus lacking VCP (vv-VCPko). vv-VCPko formed smaller
      lesions in wild-type mice but not in complement-deficient mice. Attenuation of vv
      VCPko correlated with increased accumulation of T cells at the site of infection,
      enhanced neutralizing antibody responses, and reduced viral titers. Importantly,
      depleting CD8(+) T cells together with CD4(+) T cells, which also eliminated T
      helper cell-dependent Ab responses, restored vv-VCPko to wild-type levels of
      virulence. These results suggest that VCP contributes to virulence by dampening
      both antibody and T cell responses. This work provides insight into how
      modulation of complement by poxviruses contributes to virulence and demonstrates
      that a pathogen-encoded complement regulatory protein can modulate adaptive
      immunity.

PMID- 21191013
TI  - North American porcine reproductive and respiratory syndrome viruses inhibit type
      I interferon production by plasmacytoid dendritic cells.
AB  - Although enveloped viruses typically trigger the prodigious secretion of alpha
      interferon (IFN-alpha) by plasmacytoid dendritic cells (pDC), porcine pDC remain
      quiescent when exposed to porcine reproductive and respiratory syndrome virus
      (PRRSV). This inactivity is likely due to virus-mediated interference since the
      typical IFN-alpha response by either purified or nonsorted porcine pDC to
      transmissible gastroenteritis virus (TGEV) or the Toll-like receptor 9 agonist,
      oligodeoxynucleotide (ODN) D19, was markedly reduced in the presence of PRRSV.
      Suppression occurred independently of virus viability and acidification of pDC
      early endosomes but correlated with diminished levels of IFN-alpha mRNA. This
      change was attributed to an abrogation of transcription resulting from a decrease
      in the otherwise enhanced amounts of the requisite interferon regulatory factor 7
      (IRF-7), whose gene expression in turn was limited as a consequence of a lessened
      availability of nuclear-localized signal transducer and activator of
      transcription 1 (STAT1). While PRRSV also inhibited tumor necrosis factor alpha
      (TNF-alpha) synthesis by pDC responding to either agent, only the interleukin-2
      (IL-2) and IL-6 production instigated by ODN D19 exposure was blocked. Likewise,
      PRRSV did not impact a specific TGEV-associated enhancement of IL-8 expression.
      Moreover, an augmented phosphorylation of NF-kappaB seen in activated pDC was not
      only unaffected by PRRSV but actually occurred in its presence. Thus, as
      supported by a demonstrated resilience of pDC to PRRSV infection, this pathogen
      may interact with a cell surface protein(s) to selectively impede the completion
      of cascades involved in cytokine production by stimulated pDC.

PMID- 21191014
TI  - West Nile virus differentially modulates the unfolded protein response to
      facilitate replication and immune evasion.
AB  - For intracellular survival it is imperative that viruses have the capacity to
      manipulate various cellular responses, including metabolic and biosynthetic
      pathways. The unfolded protein response (UPR) is induced by various external and
      internal stimuli, including the accumulation of misfolded proteins in the
      endoplasmic reticulum (ER). Our previous studies have indicated that the
      replication and assembly of the flavivirus West Nile virus strain Kunjin virus
      (WNV(KUN)) is intimately associated with the ER. Thus, we sought to determine
      whether the UPR was induced during WNV(KUN) infection. WNV(KUN) induces UPR
      signaling during replication, which is coordinated with peak replication.
      Interestingly, signaling is biased toward the ATF6/IRE-1 arm of the response,
      with high levels of Xbp-1 activation but negligible eukaryotic translation
      initiation factor 2alpha phosphorylation and downstream transcription. We show
      that the PERK-mediated response may partially regulate replication, since
      external UPR stimulation had a limiting effect on early replication events and
      cells deficient for PERK demonstrated increased replication and virus release.
      Significantly, we show that the WNV(KUN) hydrophobic nonstructural proteins NS4A
      and NS4B are potent inducers of the UPR, which displayed a high correlation in
      inhibiting Jak-STAT signaling in response to alpha interferon (IFN-alpha).
      Sequential removal of the transmembrane domains of NS4A showed that reducing
      hydrophobicity decreased UPR signaling and restored IFN-alpha-mediated
      activation. Overall, these results suggest that WNV(KUN) can stimulate the UPR to
      facilitate replication and that the induction of a general ER stress response,
      regulated by hydrophobic WNV(KUN) proteins, can potentiate the inhibition of the
      antiviral signaling pathway.

PMID- 21191015
TI  - Factors supporting intrathecal humoral responses following viral
      encephalomyelitis.
AB  - Central nervous system (CNS) infections and autoimmune inflammatory disorders are
      often associated with retention of antibody-secreting cells (ASC). Although
      beneficial or detrimental contributions of ASC to CNS diseases remain to be
      defined, virus-specific ASC are crucial in controlling persistent CNS infection
      following coronavirus-induced encephalomyelitis. This report characterizes
      expression kinetics of factors associated with ASC homing, differentiation, and
      survival in the spinal cord, the prominent site of coronavirus persistence.
      Infection induced a vast, gamma interferon (IFN-gamma)-dependent, prolonged
      increase in chemokine (C-X-C motif) ligand 9 (CXCL9), CXCL10, and CXCL11 mRNA,
      supporting a role for chemokine (C-X-C motif) receptor 3 (CXCR3)-mediated ASC
      recruitment. Similarly, CD4 T cell-secreted interleukin-21, a critical regulator
      of both peripheral activated B cells and CD8 T cells, was sustained during viral
      persistence. The ASC survival factors B cell-activating factor of the tumor
      necrosis factor (TNF) family (BAFF) and a proliferating-inducing ligand (APRIL)
      were also significantly elevated in the infected CNS, albeit delayed relative to
      the chemokines. Unlike IFN-gamma-dependent BAFF upregulation, APRIL induction was
      IFN-gamma independent. Moreover, both APRIL and BAFF were predominantly localized
      to astrocytes. Last, the expression kinetics of the APRIL and BAFF receptors
      coincided with CNS accumulation of ASC. Therefore, the factors associated with
      ASC migration, differentiation, and survival are all induced during acute viral
      encephalomyelitis, prior to ASC accumulation in the CNS. Importantly, the CNS
      expression kinetics implicate rapid establishment, and subsequent maintenance, of
      an environment capable of supporting differentiation and survival of protective
      antiviral ASC, recruited as plasmablasts from lymphoid organs.

PMID- 21191016
TI  - Appraising the roles of CBLL1 and the ubiquitin/proteasome system for flavivirus
      entry and replication.
AB  - The ubiquitin ligase CBLL1 (also known as HAKAI) has been proposed to be a
      critical cellular factor exploited by West Nile virus (WNV) for productive
      infection. CBLL1 has emerged as a major hit in a recent RNA interference screen
      designed to identify cellular factors required for the early stages of the WNV
      life cycle. Follow-up experiments showed that HeLa cells knocked down for CBLL1
      by a small interfering RNA (siRNA) failed to internalize WNV particles and
      resisted infection. Furthermore, depletion of a free-ubiquitin pool by the
      proteasome inhibitor MG132 abolished WNV endocytosis, suggesting that CBLL1 acts
      in concert with the ubiquitin proteasome system to mediate virus internalization.
      Here, we examined the effect of CBLL1 knockdown and proteasome inhibitors on
      infection by WNV and other flaviviruses. We identified new siRNAs that repress
      the CBLL1 protein and strongly inhibit the endocytosis of Listeria monocytogenes,
      a bacterial pathogen known to require CBLL1 to invade host cells. Strikingly,
      however, we detected efficient WNV, dengue virus, and yellow fever virus
      infection of human cells, despite potent downregulation of CBLL1 by RNA
      interference. In addition, we found that the proteasome inhibitors MG132 and
      lactacystin did not affect WNV internalization but strongly repressed flavivirus
      RNA translation and replication. Together, these data do not support a
      requirement for CBLL1 during flavivirus entry and rather suggest an essential
      role of the ubiquitin/proteasome pathway for flavivirus genome amplification.

PMID- 21191017
TI  - Adjuvant-free immunization with hemagglutinin-Fc fusion proteins as an approach
      to influenza vaccines.
AB  - The hemagglutinins (HAs) of human H1 and H3 influenza viruses and avian H5
      influenza virus were produced as recombinant fusion proteins with the human
      immunoglobulin Fc domain. Recombinant HA-human immunoglobulin Fc domain (HA-HuFc)
      proteins were secreted from baculovirus-infected insect cells as glycosylated
      oligomer HAs of the anticipated molecular mass, agglutinated red blood cells,
      were purified on protein A, and were used to immunize mice in the absence of
      adjuvant. Immunogenicity was demonstrated for all subtypes, with the serum
      samples demonstrating subtype-specific hemagglutination inhibition, epitope
      specificity similar to that seen with virus infection, and neutralization. HuFc
      tagged HAs are potential candidates for gene-to-vaccine approaches to influenza
      vaccination.

PMID- 21191018
TI  - JNK1 is required for lentivirus entry and gene transfer.
AB  - Although a lot of progress has been made in development of lentiviral vectors for
      gene therapy, the interactions of these vectors with cellular factors have not
      been explored adequately. Here we show that lentivirus infection phosphorylates
      JNK and that blocking the kinase activity of JNK decreases gene transfer in a
      dose-dependent manner, regardless of the viral envelope glycoprotein. Knockdown
      by small interfering RNA (siRNA) revealed that JNK1 but not JNK2 was required for
      productive gene transfer. The effect of JNK on gene transfer was not due to
      changes in the cell cycle, as JNK knockdown did not affect the cell cycle profile
      of target cells and even increased cell proliferation. In addition, confluent
      cell monolayers also exhibited JNK phosphorylation upon lentivirus infection and
      a dose-dependent decrease in gene transfer efficiency upon JNK inhibition. On the
      other hand, JNK activation was necessary for lentivirus internalization into the
      cell cytoplasm, while inhibition of JNK activity decreased virus entry without
      affecting binding to the cell surface. These experiments suggest that JNK is
      required for lentivirus entry into target cells and may have implications for
      gene transfer or for development of antiviral agents.

PMID- 21191019
TI  - A protein (ORF2) encoded by the latency-related gene of bovine herpesvirus 1
      interacts with Notch1 and Notch3.
AB  - Like other Alphaherpesvirinae subfamily members, bovine herpesvirus 1 (BHV-1)
      establishes latency in sensory neurons. The latency-related RNA (LR-RNA) is
      abundantly expressed in latently infected sensory neurons. An LR mutant virus
      with stop codons at the amino terminus of the first open reading frame (ORF) in
      the LR gene (ORF2) does not reactivate from latency, in part because it induces
      higher levels of apoptosis in infected neurons. ORF2 is not the only viral
      product expressed during latency, but it is important for the latency
      reactivation cycle because it inhibits apoptosis. In this study, a yeast 2-hybrid
      screen revealed that ORF2 interacted with two cellular transcription factors,
      Notch1 and Notch3. These interactions were confirmed in mouse neuroblastoma cells
      by confocal microscopy and in an in vitro "pulldown" assay. During reactivation
      from latency, Notch3 RNA levels in trigeminal ganglia were higher than those
      during latency, suggesting that Notch family members promote reactivation from
      latency or that reactivation promotes Notch expression. A plasmid expressing the
      Notch1 intercellular domain (ICD) stimulated productive infection and promoters
      that encode the viral transcription factor bICP0. The Notch3 ICD did not
      stimulate productive infection as efficiently as the Notch1 ICD and had no effect
      on bICP0 promoter activity. Plasmids expressing the Notch1 ICD or the Notch3 ICD
      trans-activated a late promoter encoding glycoprotein C. ORF2 reduced the trans
      activation potential of Notch1 and Notch3, suggesting that ORF2 interfered with
      the trans-activation potential of Notch. These studies provide evidence that
      ORF2, in addition to inhibiting apoptosis, has the potential to promote
      establishment and maintenance of latency by sequestering cellular transcription
      factors.

PMID- 21191020
TI  - Differential effects of human immunodeficiency virus type 1 Vpu on the stability
      of BST-2/tetherin.
AB  - BST-2/CD317/tetherin is a host factor that inhibits the release of HIV-1 and
      other unrelated viruses. A current model proposes that BST-2 physically tethers
      virions to the surface of virus-producing cells. The HIV-1-encoded Vpu protein
      effectively antagonizes the activity of BST-2. How Vpu accomplishes this task
      remains unclear; however, it is known that Vpu has the ability to down-modulate
      BST-2 from the cell surface. Here we analyzed the effects of Vpu on BST-2 by
      performing a series of kinetic studies with HeLa, 293T, and CEMx174 cells. Our
      results indicate that the surface downregulation of BST-2 is not due to an
      accelerated internalization or reduced recycling of internalized BST-2 but
      instead is caused by interference with the resupply of newly synthesized BST-2
      from within the cell. While our data confirm previous reports that the high-level
      expression of Vpu can cause the endoplasmic reticulum (ER)-associated degradation
      of BST-2, we found no evidence that Vpu targets endogenous BST-2 in the ER in the
      course of a viral infection. Instead, we found that Vpu acts in a post-ER
      compartment and increases the turnover of newly synthesized mature BST-2. Our
      observation that Vpu does not affect the recycling of BST-2 suggests that Vpu
      does not act directly at the cell surface but may interfere with the trafficking
      of newly synthesized BST-2 to the cell surface, resulting in the accelerated
      targeting of BST-2 to the lysosomal compartment for degradation.

PMID- 21191021
TI  - Reversal of heterochromatic silencing of quiescent herpes simplex virus type 1 by
      ICP0.
AB  - Persisting latent herpes simplex virus genomes are to some degree found in a
      heterochromatic state, and this contributes to reduced gene expression resulting
      in quiescence. We used a relatively long-term quiescent infection model in human
      fibroblasts, followed by provision of ICP0 in trans, to determine the effects of
      ICP0 on the viral chromatin state as gene expression is reactivated. Expression
      of ICP0, even at low levels, results in a reduction of higher-order chromatin
      structure and heterochromatin on quiescent viral genomes, and this effect
      precedes an increase in transcription. Concurrent with transcriptional
      activation, high levels of ICP0 expression result in the reduction of the
      heterochromatin mark trimethylated H3K9, removal of histones H3 and H4 from the
      quiescent genome, and hyperacetylation of the remaining histones. In contrast,
      low levels of ICP0 did not appreciably change the levels of histones on the viral
      genome. These results indicate that ICP0 activity ultimately affects chromatin
      structure of quiescent genomes at multiple levels, including higher-order
      chromatin structure, histone modifications, and histone association.
      Additionally, the level of ICP0 expression affected its ability to change
      chromatin structure but not to reactivate gene expression. While these
      observations suggest that some of the effects on chromatin structure are possibly
      not direct, they also suggest that ICP0 exerts its effects through multiple
      mechanisms.

PMID- 21191023
TI  - Experimental adaptation of an RNA virus mimics natural evolution.
AB  - Identification of virulence determinants of viruses is of critical importance in
      virology. In search of such determinants, virologists traditionally utilize
      comparative genomics between a virulent and an avirulent virus strain and
      construct chimeras to map their locations. Subsequent comparison reveals sequence
      differences, and through analyses of site-directed mutants, key residues are
      identified. In the absence of a naturally occurring virulent strain, an avirulent
      strain can be functionally converted to a virulent variant via an experimental
      evolutionary approach. However, the concern remains whether experimentally
      evolved virulence determinants mimic those that have evolved naturally. To
      provide a direct comparison, we exploited a plant RNA virus, soybean mosaic virus
      (SMV), and its natural host, soybean. Through a serial in vivo passage
      experiment, the molecularly cloned genome of an avirulent SMV strain was
      converted to virulent variants on functionally immune soybean genotypes harboring
      resistance factor(s) from the complex Rsv1 locus. Several of the experimentally
      evolved virulence determinants were identical to those discovered through a
      comparative genomic approach with a naturally evolved virulent strain. Thus, our
      observations validate an experimental evolutionary approach to identify relevant
      virulence determinants of an RNA virus.

PMID- 21191022
TI  - Rhesus rotavirus entry into a polarized epithelium is endocytosis dependent and
      involves sequential VP4 conformational changes.
AB  - Rotavirus (RV) cell entry is an incompletely understood process, involving VP4
      and VP7, the viral proteins composing the outermost layer of the nonenveloped RV
      triple-layered icosahedral particle (TLP), encasing VP6. VP4 can exist in three
      conformational states: soluble, cleaved spike, and folded back. In order to
      better understand the events leading to RV entry, we established a detection
      system to image input virus by monitoring the rhesus RV (RRV) antigens VP4, VP6,
      and VP7 at very early times postinfection. We provide evidence that decapsidation
      occurs directly after cell membrane penetration. We also demonstrate that several
      VP4 and VP7 conformational changes take place during entry. In particular, we
      detected, for the first time, the generation of folded-back VP5 in the context of
      the initiation of infection. Folded-back VP5 appears to be limited to the entry
      step. We furthermore demonstrate that RRV enters the cell cytoplasm through an
      endocytosis pathway. The endocytosis hypothesis is supported by the
      colocalization of RRV antigens with the early endosome markers Rab4 and Rab5.
      Finally, we provide evidence that the entry process is likely dependent on the
      endocytic Ca(2+) concentration, as bafilomycin A1 treatment as well as an
      augmentation of the extracellular calcium reservoir using CaEGTA, which both lead
      to an elevated intraendosomal calcium concentration, resulted in the accumulation
      of intact virions in the actin network. Together, these findings suggest that
      internalization, decapsidation, and cell membrane penetration involve
      endocytosis, calcium-dependent uncoating, and VP4 conformational changes,
      including a fold-back.

PMID- 21191024
TI  - Rice dwarf viruses with dysfunctional genomes generated in plants are filtered
      out in vector insects: implications for the origin of the virus.
AB  - Rice dwarf virus (RDV), with 12 double-stranded RNA (dsRNA) genome segments (S1
      to S12), replicates in and is transmitted by vector insects. The RDV-plant host
      vector insect system allows us to examine the evolution, adaptation, and
      population genetics of a plant virus. We compared the effects of long-term
      maintenance of RDV on population structures in its two hosts. The maintenance of
      RDV in rice plants for several years resulted in gradual accumulation of nonsense
      mutations in S2 and S10, absence of expression of the encoded proteins, and
      complete loss of transmissibility. RDV maintained in cultured insect cells for 6
      years retained an intact protein-encoding genome. Thus, the structural P2 protein
      encoded by S2 and the nonstructural Pns10 protein encoded by S10 of RDV are
      subject to different selective pressures in the two hosts, and mutations
      accumulating in the host plant are detrimental in vector insects. However, one
      round of propagation in insect cells or individuals purged the populations of RDV
      that had accumulated deleterious mutations in host plants, with exclusive
      survival of fully competent RDV. Our results suggest that during the course of
      evolution, an ancestral form of RDV, of insect virus origin, might have acquired
      the ability to replicate in a host plant, given its reproducible mutations in the
      host plant that abolish vector transmissibility and viability in nature.

PMID- 21191025
TI  - Growth inhibition of HeLa cells is a conserved feature of high-risk human
      papillomavirus E8^E2C proteins and can also be achieved by an artificial
      repressor protein.
AB  - Infections with certain human papillomaviruses (HPV), such as type 16 (HPV16),
      18, or 31, are a necessary risk factor for the development of cervical cancer.
      Transcript analyses of several HPV revealed that the viral E2 gene encodes both
      the E2 regulator protein and the E8?E2C protein, which differ in their amino
      termini. Up to now, functional studies have focused on HPV31 E8?E2C and
      demonstrated that it is a potent repressor of viral transcription and
      replication. However, recent analyses of HPV16 genomes have suggested that E8?E2C
      proteins may differ in their activities. Therefore, we performed a comparative
      analysis of E8?E2C proteins of HPV16, -18, and -31. All E8?E2C proteins potently
      inhibited HPV E6/E7 oncogene promoters, and also displayed long-distance
      transcriptional-repression activities. Furthermore, the expression of all E8?E2C
      proteins inhibited the growth of HeLa cells. Expression of E8?E2C proteins
      rapidly increased the protein levels of the E6 and E7 targets p53 and p21,
      consistent with the repression of the endogenous HPV18 E6/E7 promoter. All E8?E2C
      proteins induced G(1) arrest more efficiently than E2 proteins and activated
      senescence markers. Furthermore, we demonstrate that the 31E8 domain can be
      functionally replaced by the KRAB repression domain derived from KOX1. The KRAB
      E2C fusion protein possesses long-distance transcriptional-repression activity
      and inhibits the growth of HeLa cells comparably to E8?E2C. Taken together, our
      results suggest that the E8?E2C proteins of HPV16, -18, and -31 are highly
      conserved transcriptional repressors that inhibit the growth of HeLa cells by
      repression of E6/E7 transcription but do not have proapoptotic activities.

PMID- 21191026
TI  - Structural comparison of HIV-1 envelope spikes with and without the V1/V2 loop.
AB  - We have used cryoelectron tomography of vitreous-ice-embedded HIV-1 virions to
      compare the envelope (Env) spikes of a wild-type strain with those of a mutant
      strain in which the V1/V2 loop has been deleted. Deletion of V1/V2 results in a
      spike with far more structural heterogeneity than is observed in the wild type,
      likely reflecting greatly enhanced gp120 protomer flexibility. A major difference
      between the two forms is a pronounced loss of mass from the "peak" of the native
      Env spike. The apparent loss of contact among three gp120 protomers likely
      accounts for the more open structure, heterogeneity in configuration, and
      previous observations that broadly neutralizing epitopes and reactive sites on
      other structural elements are more exposed in such constructs.

PMID- 21191027
TI  - Multiple interactions between the ESCRT machinery and arrestin-related proteins:
      implications for PPXY-dependent budding.
AB  - Late domains are short peptide sequences encoded by enveloped viruses to promote
      the final separation of the nascent virus from the infected cell. These amino
      acid motifs facilitate viral egress by interacting with components of the ESCRT
      (endosomal sorting complex required for transport) machinery, ultimately leading
      to membrane scission by recruiting ESCRT-III to the site of viral budding. PPXY
      late (L) domains present in viruses such as murine leukemia virus (MLV) or human
      T-cell leukemia virus type 1 (HTLV-1) access the ESCRT pathway via interaction
      with HECT ubiquitin ligases (WWP1, WWP2, and Itch). However, the mechanism of
      ESCRT-III recruitment in this context remains elusive. In this study, we tested
      the arrestin-related trafficking (ART) proteins, namely, ARRDC1 (arrestin domain
      containing protein 1) to ARRDC4 and TXNIP (thioredoxin-interacting protein), for
      their ability to function as adaptors between HECT ubiquitin ligases and the core
      ESCRT machinery in PPXY-dependent budding. We present several lines of evidence
      in support of such a role: ARTs interact with HECT ubiquitin ligases, and they
      also exhibit multiple interactions with components of the ESCRT pathway, namely,
      ALIX and Tsg101, and perhaps with an as yet unidentified factor. Additionally,
      the ARTs can be recruited to the site of viral budding, and their overexpression
      results in a PPXY-specific inhibition of MLV budding. Lastly, we show that WWP1
      changes the ubiquitination status of ARRDC1, suggesting that the ARTs may provide
      a platform for ubiquitination in PPXY-dependent budding. Taken together, our
      results support a model whereby ARTs are involved in PPXY-mediated budding by
      interacting with HECT ubiquitin ligases and providing several alternative routes
      for ESCRT-III recruitment.

PMID- 21191028
TI  - Initiation of Epstein-Barr virus lytic replication requires transcription and the
      formation of a stable RNA-DNA hybrid molecule at OriLyt.
AB  - The genetic elements of herpesvirus origins of lytic replication have been
      characterized in detail; however, much remains to be elucidated concerning their
      functional role in replication initiation. In the case of the Epstein-Barr virus
      (EBV), we have found that in addition to the two well-defined critical elements
      required for lytic replication (the upstream and downstream essential elements,
      UEE and DEE), the origin of lytic replication (OriLyt) also requires the presence
      of a GC-rich RNA in cis. The BHLF1 transcript is similar to the essential K5
      transcript identified at the Kaposi's sarcoma-associated herpesvirus OriLyt. We
      have found that truncation of the BHLF1 transcript or deletion of the TATA box,
      but not the putative ATG initiation codon, reduce OriLyt function to background
      levels. By using an antibody specific for RNA-DNA hybrid molecules, we found the
      BHLF1 RNA stably annealed to its DNA template during the early steps of lytic
      reactivation. Furthermore, expression of human RNase H1, which degrades RNA in
      RNA-DNA hybrids, drastically reduces OriLyt-dependent DNA replication as well as
      recruitment of the viral single-stranded DNA binding protein BALF2 to OriLyt.
      These studies suggest that a GC-rich OriLyt transcript is an important component
      of gammaherpesvirus lytic origins and is required for initial strand separation
      and loading of core replication proteins.

PMID- 21191029
TI  - Antiviral RNA interference responses induced by Semliki Forest virus infection of
      mosquito cells: characterization, origin, and frequency-dependent functions of
      virus-derived small interfering RNAs.
AB  - RNA interference (RNAi) is an important mosquito defense mechanism against
      arbovirus infection. In this paper we study the processes underlying antiviral
      RNAi in Aedes albopictus-derived U4.4 mosquito cells infected with Semliki Forest
      virus (SFV) (Togaviridae; Alphavirus). The production of virus-derived small
      interfering RNAs (viRNAs) from viral double-stranded RNA (dsRNA) is a key event
      in this host response. dsRNA could be formed by RNA replication intermediates, by
      secondary structures in RNA genomes or antigenomes, or by both. Which of these
      dsRNAs is the substrate for the generation of viRNAs is a fundamental question.
      Here we used deep sequencing of viRNAs and bioinformatic analysis of RNA
      secondary structures to gain insights into the characteristics and origins of
      viRNAs. An asymmetric distribution of SFV-derived viRNAs with notable areas of
      high-level viRNA production (hot spots) and no or a low frequency of viRNA
      production (cold spots) along the length of the viral genome with a slight bias
      toward the production of genome-derived viRNAs over antigenome-derived viRNAs was
      observed. Bioinformatic analysis suggests that hot spots of viRNA production are
      rarely but not generally associated with putative secondary structures in the SFV
      genome, suggesting that most viRNAs are derived from replicative dsRNA. A pattern
      of viRNAs almost identical to those of A. albopictus cells was observed for Aedes
      aegypti-derived Aag2 cells, suggesting common mechanisms that lead to viRNA
      production. Hot-spot viRNAs were found to be significantly less efficient at
      mediating antiviral RNAi than cold-spot viRNAs, pointing toward a nucleic acid
      based viral decoy mechanism to evade the RNAi response.

PMID- 21191030
TI  - Roles of VP4 and NSP1 in determining the distinctive replication capacities of
      simian rotavirus RRV and bovine rotavirus UK in the mouse biliary tract.
AB  - Rotavirus replication and virulence are strongly influenced by virus strain and
      host species. The rotavirus proteins VP3, VP4, VP7, NSP1, and NSP4 have all been
      implicated in strain and species restriction of replication; however, the
      mechanisms have not been fully determined. Simian (RRV) and bovine (UK)
      rotaviruses have distinctive replication capacities in mouse extraintestinal
      organs such as the biliary tract. Using reassortants between UK and RRV, we
      previously demonstrated that the differential replication of these viruses in
      mouse embryonic fibroblasts is determined by the respective NSP1 proteins, which
      differ substantially in their abilities to degrade interferon (IFN) regulatory
      factor 3 (IRF3) and suppress the type I IFN response. In this study, we used an
      in vivo model of rotavirus infection of mouse gallbladder with UK * RRV
      reassortants to study the genetic and mechanistic basis of systemic rotavirus
      replication. We found that the low-replication phenotype of UK in biliary tissues
      was conferred by UK VP4 and that the high-replication phenotype of RRV was
      conferred by RRV VP4 and NSP1. Viruses with RRV VP4 entered cultured mouse
      cholangiocytes more efficiently than did those with UK VP4. Reassortants with RRV
      VP4 and UK NSP1 genes induced high levels of expression of IRF3-dependent p54 in
      biliary tissues, and their replication was increased 3-fold in IFN-alpha/beta and
      -gamma receptor or STAT1 knockout (KO) mice compared to wild-type mice. Our data
      indicate that systemic rotavirus strain-specific replication in the murine
      biliary tract is determined by both viral entry mediated by VP4 and viral
      antagonism of the host innate immune response mediated by NSP1.

PMID- 21191031
TI  - Population modeling of influenza A/H1N1 virus kinetics and symptom dynamics.
AB  - Influenza virus kinetics (VK) is used as a surrogate of infectiousness, while the
      natural history of influenza is described by symptom dynamics (SD). We used an
      original virus kinetics/symptom dynamics (VKSD) model to characterize human
      influenza virus infection and illness, based on a population approach. We
      combined structural equations and a statistical model to describe intra- and
      interindividual variability. The structural equations described influenza based
      on the target epithelial cells, the virus, the innate host response, and systemic
      symptoms. The model was fitted to individual VK and SD data obtained from 44
      volunteers experimentally challenged with influenza A/H1N1 virus. Infection and
      illness parameters were calculated from best-fitted model estimates. We predicted
      that the cytokine level and NK cell activity would peak at days 2.2 and 4.2 after
      inoculation, respectively. Infectiousness, measured as the area under the VK
      curve above a viral titer threshold, lasted between 7.0 and 1.3 days and was 15
      times lower in participants without systemic symptoms than in those with systemic
      symptoms (P < 0.001). The latent period, defined as the time between inoculation
      and infectiousness, varied from 0.7 to 1.9 days. The incubation period, defined
      as the time from inoculation to first symptoms, varied from 1.0 to 2.4 days. Our
      approach extends previous work by including the innate response and providing
      realistic estimates of infection and illness parameters, taking into account the
      strong interindividual variability. This approach could help to optimize studies
      of influenza VK and SD and to predict the effect of antivirals on infectiousness
      and symptoms.

PMID- 21191032
TI  - Proteomic pathway analysis reveals inflammation increases myeloid-derived
      suppressor cell resistance to apoptosis.
AB  - Myeloid-derived suppressor cells (MDSC) accumulate in patients and animals with
      cancer where they mediate systemic immune suppression and obstruct immune-based
      cancer therapies. We have previously demonstrated that inflammation, which
      frequently accompanies tumor onset and progression, increases the rate of
      accumulation and the suppressive potency of MDSC. To determine how inflammation
      enhances MDSC levels and activity we used mass spectrometry to identify proteins
      produced by MDSC induced in highly inflammatory settings. Proteomic pathway
      analysis identified the Fas pathway and caspase network proteins, leading us to
      hypothesize that inflammation enhances MDSC accumulation by increasing MDSC
      resistance to Fas-mediated apoptosis. The MS findings were validated and extended
      by biological studies. Using activated caspase 3 and caspase 8 as indicators of
      apoptosis, flow cytometry, confocal microscopy, and Western blot analyses
      demonstrated that inflammation-induced MDSC treated with a Fas agonist contain
      lower levels of activated caspases, suggesting that inflammation enhances
      resistance to Fas-mediated apoptosis. Resistance to Fas-mediated apoptosis was
      confirmed by viability studies of MDSC treated with a Fas agonist. These results
      suggest that an inflammatory environment, which is frequently present in tumor
      bearing individuals, protects MDSC against extrinsic-induced apoptosis resulting
      in MDSC with a longer in vivo half-life, and may explain why MDSC accumulate more
      rapidly and to higher levels in inflammatory settings.

PMID- 21191034
TI  - Psychometric assessment of the Emotional Reactions Instrument-Korean (ERI-K) to
      measure Korean children's emotional reaction to hospitalization.
AB  - The purpose of this study was to test psychometric properties of the Emotional
      Reactions Instrument-Korean (ERI-K). A convenience sample of 170 hospitalized
      Korean children was recruited. Each child was asked to describe how she or he
      felt during hospitalization, through the ERI-K and the Facial Affective Scale.
      Surprisingly, children reported lower levels of negative emotions and physical
      discomfort and a moderate level of positive emotion (Happy, Good). Internal
      consistency reliability of .88 for the 14-item scale provides strong support for
      reliability. Construct validity was supported by item-to-total correlations
      ranging between .42 and .65. Exploratory factor analysis identified two factors
      that explained 54% of the variance. Further testing of the ERI-K is recommended
      to provide additional evidence of psychometric adequacy across Korean
      populations.

PMID- 21191033
TI  - Time-resolved quantitative proteome analysis of in vivo intestinal development.
AB  - Postnatal intestinal development is a very dynamic process characterized by
      substantial morphological changes that coincide with functional adaption to the
      nutritional change from a diet rich in fat (milk) to a diet rich in carbohydrates
      on from weaning. Time-resolved studies of intestinal development have so far been
      limited to investigation at the transcription level or to single or few proteins
      at a time. In the present study, we elucidate proteomic changes of primary
      intestinal epithelial cells from jejunum during early suckling (1-7 days of age),
      middle suckling (7-14 days), and weaning period (14-35 days) in mice, using a
      label-free proteomics approach. We show differential expression of 520 proteins
      during intestinal development and a pronounced change of the proteome during the
      middle suckling period and weaning. Proteins involved in several metabolic
      processes were found differentially expressed along the development. The temporal
      expression profiles of enzymes of the glycolysis were found to correlate with the
      increase in carbohydrate uptake at weaning, whereas the abundance changes of
      proteins involved in fatty acid metabolism as well as lactose metabolism
      indicated a nondiet driven preparation for the nutritional change at weaning.
      Further, we report the developmental abundance changes of proteins playing a
      vital role in the neonatal acquisition of passive immunity. In addition,
      different isoforms of several proteins were quantified, which may contribute to a
      better understanding of the roles of the specific isoforms in the small
      intestine. In summary, we provide a first, time-resolved proteome profile of
      intestinal epithelial cells along postnatal intestinal development.

PMID- 21191035
TI  - Disclosure of HIV infection among Israeli men who have sex with men.
AB  - A descriptive, cross-sectional study was conducted to explore disclosure
      decisions regarding potential HIV infection by men who have sex with men (MSM).
      The sample consisted of 104 Israeli MSM. A questionnaire based on the theory of
      reasoned action was used for data determination. The questionnaire deals with
      beliefs, attitudes, and disclosure intentions. Results showed that only 30% of
      respondents intended to disclose potential HIV infection. A total of 70% of those
      who intended to disclose would choose to disclose the information to their
      brother/sister, two thirds to their mother, and only about 50% to their father.
      All components of the theory have an effect on MSM intentions of disclosure to
      others. In addition, behavioral beliefs, that is, MSM beliefs of the consequences
      of disclosure, were found to be the most significant predictor of behavioral
      intention. Research recommendations include the promotion of positive behavioral
      attitudes toward disclosure, leading to an increase in behavioral intentions of
      disclosure.

PMID- 21191036
TI  - Hispanic women's experiences with substance abuse, intimate partner violence, and
      risk for HIV.
AB  - Hispanic females are disproportionately affected by substance abuse, intimate
      partner violence, and HIV. Despite these disparities, research describing the
      cultural and gender-specific experiences of Hispanic women with regard to these
      conditions is lacking. THE PURPOSE: Transplantadas en otro mundo (Uprooted in
      another world), El criador de abuso (The breeding ground of abuse), and Rompiendo
      el silencio (Breaking the silence). This study supports the importance of
      addressing substance abuse, violence, and risk for HIV in an integrated manner
      and stresses the importance of addressing associated cultural factors (e.g.,
      acculturation, machismo ) in interventions targeting Hispanics.

PMID- 21191037
TI  - Fa'afaletui: a framework for the promotion of renal health in an Australian
      Samoan community.
AB  - PURPOSE: Samoan communities in Australia exhibit a disproportionate rate of
      kidney disease compared with other Australians. This article describes a research
      project that used a culturally sensitive framework, Fa'afaletui, to help reduce
      the barriers of language and culture and increase our understanding of the
      factors contributing to kidney disease, in one Samoan community in Australia.
      DESIGN: Semistructured group interviews were undertaken with Samoan community
      families and groups. The interviews were analyzed according to key concepts
      embedded in the Fa'afaletui framework. FINDINGS: Four factors associated with
      health risks in this Samoan community emerged: diet and exercise, issues related
      to the collective (incorporating the village, church, and family), tapu or
      cultural protocols, and the importance of language. CONCLUSIONS: The findings
      suggest that future kidney health promotion initiatives within this Samoan
      community will be more effective if they are sensitive to Samoan cultural norms,
      language, and context.

PMID- 21191038
TI  - The integral role of food in Native Hawaiian migrants' perceptions of health and
      well-being.
AB  - PURPOSE: Obesity is prevalent among Native Hawaiians, but the relationship
      between food and perceptions of health and well-being is not well understood. The
      purpose was to explore the role of food in Native Hawaiians' perceptions of
      health and well-being. DESIGN: A qualitative descriptive design was used. Twenty
      seven Native Hawaiian participants in Las Vegas took part in semistructured
      interviews. RESULTS: Participants expressed that food can be dangerous to health.
      However, eating Hawaiian food seems to relieve homesickness, and they
      occasionally indulge in binge overeating. CONCLUSIONS: Hawaiian food plays an
      important role in participants' health and well-being. Participants' concurrent
      attraction to Hawaiian-style food and desire to avoid unhealthy food create a
      challenging struggle. IMPLICATIONS: To support cultural connectedness, Native
      Hawaiians can be encouraged to expend consumed calories in physical activity as
      their ancestors did. Discussing nutrition from a family framework might be
      helpful to Native Hawaiians.

PMID- 21191039
TI  - Provider characteristics desired by African American women in prenatal care.
AB  - PURPOSE: The purpose of this study was to describe provider characteristics
      African American pregnant women identified as important when interacting with
      their prenatal care providers in an outpatient office setting. STUDY DESIGN: A
      descriptive qualitative design was used to explore provider characteristics
      desired by African American women receiving prenatal care at two inner-city
      hospital-based obstetric clinics. A total of 22 African American women between
      the ages of 19 and 28 years participated in the study. FINDINGS: Four major
      provider characteristic themes emerged from the data: (a) demonstrating quality
      patient-provider communication, (b) providing continuity of care, (c) treating
      the women with respect, and (d) delivering compassionate care. DISCUSSION: An
      overarching theme revealed by the data analysis was the desire by African
      American women in this study to have their prenatal providers know and remember
      them. They wanted their providers to understand the context of their lives from
      their prenatal interactions. Incorporating findings from this study to improve
      patient-provider interactions during prenatal care could provide an increased
      understanding of the many complex variables affecting African American women's
      lives. IMPLICATIONS: Prenatal care provides an opportunity for African American
      women to develop a trusting relationship with a provider. Developing models of
      prenatal care congruent with the realities of African American women's lives has
      the potential to improve patient- provider interactions and potentially affect
      birth outcomes.

PMID- 21191040
TI  - Conducting transcultural research: critical thinking in Thailand.
AB  - Little has been written to help researchers prepare for the unique challenges of
      conducting transcultural research. The purpose of this article is to discuss
      issues that arose during the planning and execution of a transcultural study
      designed to compare critical thinking in Thailand and the United States. The
      challenges of identifying a research site, selecting participants, incorporating
      Thai research into the literature review, traveling and living in a foreign
      culture, overcoming cultural barriers to research, and strengthening internal
      validity and reliability are addressed.

PMID- 21191041
TI  - A celebration of a life of commitment to transcultural nursing: opening of the
      Madeleine M. Leininger Collection on Human Caring and Transcultural Nursing.

PMID- 21191043
TI  - Synaptic tagging, evaluation of memories, and the distal reward problem.
AB  - Long-term synaptic plasticity exhibits distinct phases. The synaptic tagging
      hypothesis suggests an early phase in which synapses are prepared, or "tagged,"
      for protein capture, and a late phase in which those proteins are integrated into
      the synapses to achieve memory consolidation. The synapse specificity of the tags
      is consistent with conventional neural network models of associative memory.
      Memory consolidation through protein synthesis, however, is neuron specific, and
      its functional role in those models has not been assessed. Here, using a
      theoretical network model, we test the tagging hypothesis on its potential to
      prolong memory lifetimes in an online-learning paradigm. We find that protein
      synthesis, though not synapse specific, prolongs memory lifetimes if it is used
      to evaluate memory items on a cellular level. In our model we assume that only
      "important" memory items evoke protein synthesis such that these become more
      stable than "unimportant" items, which do not evoke protein synthesis. The
      network model comprises an equilibrium distribution of synaptic states that is
      very susceptible to the storage of new items: Most synapses are in a state in
      which they are plastic and can be changed easily, whereas only those synapses
      that are essential for the retrieval of the important memory items are in the
      stable late phase. The model can solve the distal reward problem, where the
      initial exposure of a memory item and its evaluation are temporally separated.
      Synaptic tagging hence provides a viable mechanism to consolidate and evaluate
      memories on a synaptic basis.

PMID- 21191042
TI  - The anaphase promoting complex is required for memory function in mice.
AB  - Learning and memory processes critically involve the orchestrated regulation of
      de novo protein synthesis. On the other hand it has become clear that regulated
      protein degradation also plays a major role in neuronal plasticity and learning
      behavior. One of the key pathways mediating protein degradation is proteosomal
      protein destruction. The anaphase-promoting complex/cyclosome (APC/C) is an E3
      ubiquitin ligase that targets proteins for proteosomal degradation by the 26S
      proteasome. While the APC/C is essential for cell cycle progression it is also
      expressed in postmitotic neurons where it has been implicated with axonal
      outgrowth and neuronal survival. In this study we addressed the role of APC/C in
      learning and memory function by generating mice that lack the essential subunit
      APC2 from excitatory neurons of the adult forebrain. Those animals are viable but
      exhibit a severe impairment in the ability to extinct fear memories, a process
      critical for the treatment of anxiety diseases such as phobia or post-traumatic
      stress disorder. Since deregulated protein degradation and APC/C activity has
      been implicated with neurodegeneration we also analyzed the effect of Apc2
      deletion in a mouse model for Alzheimer's disease. In our experimental setting
      loss of APC2 form principle forebrain neurons did not affect the course of
      pathology in an Alzheimer's disease mouse model. In conclusion, our data provides
      genetic evidence that APC/C activity in the adult forebrain is required for
      cognitive function.

PMID- 21191044
TI  - Molecular determinants of potent P2X2 antagonism identified by functional
      analysis, mutagenesis, and homology docking.
AB  - P2X2 receptors are members of the ATP-gated P2X family of cation channels, and
      they participate in neurotransmission in sympathetic ganglia and interneurons.
      Here, we identified 7,7'-(carbonylbis(imino-3,1-phenylenecarbonylimino-3,1-(4
      methyl-phenylene)carbonylimino))bis(1-methoxy-naphthalene-3,6-disulfonic acid)
      tetrasodium salt (NF770) as a nanomolar-potent competitive P2X2 receptor
      antagonist within a series of 139 suramin derivatives. Three structural
      determinants contributed to the inhibition of P2X2 receptors by NF770: 1) a
      "large urea" structure with two symmetric phenylenecarbonylimino groups; 2)
      attachment of the naphthalene moiety in position 7,7'; and 3) the specific
      position of two sulfonic acid groups (3,3'; 6,6') and of one methoxy group (1,1')
      at the naphthalene moiety. This structure-activity relationship was interpreted
      using a rat P2X2 homology model based on the crystal structure of the closed
      zebrafish P2X4 receptor. Docking of the suramin derivatives into the modeled ATP
      binding pocket provides a uniform explanation for the observed differences in
      inhibitory potencies. Changes in the chemical structure that increase the
      inhibitory potency of the suramin derivatives improved the spatial orientation
      within the ATP-binding pocket to allow for stronger polar interactions of
      functional groups with Gly72, Glu167, or Arg290. Gly72 is responsible for the
      orientation of the methoxy group close to Arg290 or Glu167. Combined mutational
      and functional analysis confirmed that residues Gly72 and Glu167 are as important
      for ATP binding as Arg290, the ATP-binding role of which has been shown in
      previous studies. The in silico prediction of Gly72 and Glu167 as ATP-binding
      residues strongly supports the validity of our homology docking.

PMID- 21191045
TI  - Preclinical pharmacology, antitumor activity, and development of pharmacodynamic
      markers for the novel, potent AKT inhibitor CCT128930.
AB  - AKT is frequently deregulated in cancer, making it an attractive anticancer drug
      target. CCT128930 is a novel ATP-competitive AKT inhibitor discovered using
      fragment- and structure-based approaches. It is a potent, advanced lead
      pyrrolopyrimidine compound exhibiting selectivity for AKT over PKA, achieved by
      targeting a single amino acid difference. CCT128930 exhibited marked
      antiproliferative activity and inhibited the phosphorylation of a range of AKT
      substrates in multiple tumor cell lines in vitro, consistent with AKT inhibition.
      CCT128930 caused a G(1) arrest in PTEN-null U87MG human glioblastoma cells,
      consistent with AKT pathway blockade. Pharmacokinetic studies established that
      potentially active concentrations of CCT128930 could be achieved in human tumor
      xenografts. Furthermore, CCT128930 also blocked the phosphorylation of several
      downstream AKT biomarkers in U87MG tumor xenografts, indicating AKT inhibition in
      vivo. Antitumor activity was observed with CCT128930 in U87MG and HER2-positive,
      PIK3CA-mutant BT474 human breast cancer xenografts, consistent with its
      pharmacokinetic and pharmacodynamic properties. A quantitative immunofluorescence
      assay to measure the phosphorylation and total protein expression of the AKT
      substrate PRAS40 in hair follicles is presented. Significant decreases in pThr246
      PRAS40 occurred in CCT128930-treated mouse whisker follicles in vivo and human
      hair follicles treated ex vivo, with minimal changes in total PRAS40. In
      conclusion, CCT128930 is a novel, selective, and potent AKT inhibitor that blocks
      AKT activity in vitro and in vivo and induces marked antitumor responses. We have
      also developed a novel biomarker assay for the inhibition of AKT in human hair
      follicles, which is currently being used in clinical trials.

PMID- 21191046
TI  - Performance of the Aptima high-risk human papillomavirus mRNA assay in a referral
      population in comparison with Hybrid Capture 2 and cytology.
AB  - This study compared the Aptima human papillomavirus (HPV) (AHPV; Gen-Probe
      Incorporated) assay, which detects E6/E7 mRNA from 14 high-risk types, the Hybrid
      Capture 2 HPV DNA (HC2; Qiagen Incorporated) test, and repeat cytology for their
      ability to detect high-grade cervical lesions (cervical intraepithelial neoplasia
      grade 2+ [CIN2+]) in women referred to colposcopy due to an abnormal Papanicolaou
      (Pap) smear. A total of 424 clinical specimens, stored in liquid-based cytology
      (LBC) vials at room temperature for up to 3 years, were tested by repeat
      cytology, the AHPV assay, and the HC2 test. Assay results were compared to each
      other and to histology results. The overall agreement between the AHPV assay and
      the HC2 test was 88.4%. The sensitivity (specificity) of cytology, the HC2 test,
      and the AHPV assay for the detection of CIN2+ was 84.9% (66.3%), 91.3% (61.0%),
      and 91.7% (75.0%) and for the detection of CIN3+ was 93.9% (54.4%), 95.7%
      (46.0%), and 98.2% (56.3%), respectively. Of the disease-positive specimens
      containing high-risk HPV (HR HPV) DNA as determined by Linear Array (Roche
      Diagnostics), the AHPV assay missed 3 CIN2 and 1 microfocal CIN3 specimen, while
      the HC2 test missed 6 CIN2, 4 CIN3, and 1 cervical carcinoma specimen. The AHPV
      assay had a sensitivity similar to but a specificity significantly higher (P <
      0.0001) than the HC2 test for the detection of CIN2+. The AHPV assay was
      significantly more sensitive (P = 0.0041) and significantly more specific (P =
      0.0163) than cytology for the detection of disease (CIN2+).

PMID- 21191047
TI  - Rapid detection of fluoroquinolone-resistant and heteroresistant Mycobacterium
      tuberculosis by use of sloppy molecular beacons and dual melting-temperature
      codes in a real-time PCR assay.
AB  - Fluoroquinolones (FQ) are important second-line drugs to treat tuberculosis;
      however, FQ resistance is an emerging problem. Resistance has been mainly
      attributed to mutations in a 21-bp region of the Mycobacterium tuberculosis gyrA
      gene, often called the quinolone resistance-determining region (QRDR). We have
      developed a simple, rapid, and specific assay to detect FQ resistance-determining
      QRDR mutations. The assay amplifies the M. tuberculosis gyrA QRDR in an
      asymmetrical PCR followed by probing with two sloppy molecular beacons (SMBs)
      spanning the entire QRDR. Mutations are detected by melting temperature (T(m))
      shifts that occur when the SMBs bind to mismatched sequences. By testing DNA
      targets corresponding to all known QRDR mutations, we found that one or both of
      the SMBs produced a T(m) shift of at least 3.6 degrees C for each mutation,
      making mutation detection very robust. The assay was also able to identify
      mixtures of wild-type and mutant DNA, with QRDR mutants identified in samples
      containing as little as 5 to 10% mutant DNA. The assay was blindly validated for
      its ability to identify the QRDR mutations on DNA extracted from clinical M.
      tuberculosis strains. Fifty QRDR wild-type samples, 34 QRDR mutant samples, and 8
      heteroresistant samples containing mixtures of wild-type and mutant DNA were
      analyzed. The results showed 100% concordance to conventional DNA sequencing,
      including a complete identification of all of the mixtures. This SMB T(m) shift
      assay will be a valuable molecular tool to rapidly detect FQ resistance and to
      detect the emergence of FQ heteroresistance in clinical samples from tuberculosis
      patients.

PMID- 21191048
TI  - Reassessment of Stenotrophomonas maltophilia phenotype.
AB  - Standard microbiology references describe Stenotrophomonas maltophilia as oxidase
      negative and variable with respect to utilization of lactose and sucrose.
      Analysis of a collection of 766 S. maltophilia isolates indicated that
      approximately 20% are oxidase positive and that this species should be
      reevaluated for other phenotypes, including oxidative fermentation of lactose and
      sucrose.

PMID- 21191049
TI  - Pulsed-field gel electrophoresis genotyping of Taylorella equigenitalis isolates
      collected in the United States from 1978 to 2010.
AB  - Taylorella equigenitalis is the etiologic agent of contagious equine metritis
      (CEM), a venereal disease of horses. A total of 82 strains of T. equigenitalis
      isolated in the United States were analyzed by pulsed-field gel electrophoresis
      (PFGE) after digestion of genomic DNA with restriction enzyme ApaI. Twenty-eight
      of those strains isolated from horses in the 2009 U.S. outbreak (CEM09) were
      further analyzed with NotI and NaeI enzymes. When ApaI alone was used for
      analysis, the 82 isolates clustered into 15 different genotypes that clearly
      defined groups of horses with known epidemiological connections. The PFGE
      profiles of the CEM09 isolates were indistinguishable after digestion with ApaI,
      NotI, and NaeI and did not match those of isolates from previous U.S. outbreaks
      in 1978 and 2006 or of any other isolate from the National Veterinary Services
      Laboratories (NVSL) culture library. Coupled with the fact that the CEM09
      isolates are epidemiologically related, these results suggest a common source for
      the outbreak not linked to previous occurrences of CEM in the United States.

PMID- 21191050
TI  - Current molecular epidemiology of Lassa virus in Nigeria.
AB  - Recent Lassa virus strains from Nigeria were completely or partially sequenced.
      Phylogenetic analysis revealed the predominance of lineage II and III strains,
      the existence of a previously undescribed (sub)lineage in Nigeria, and the
      directional spread of virus in the southern part of the country. The Bayesian
      analysis also provided estimates for divergence times within the Lassa virus
      clade.

PMID- 21191051
TI  - Extraction of MS2 phage RNA from upper respiratory tract specimens by use of flat
      glass devices.
AB  - The isolation of pure nucleic acids from clinical samples is a crucial step in
      the molecular diagnosis of viral infections by nucleic acid testing (NAT). In
      this study, novel flat glass devices (cards) were demonstrated to support the
      rapid and efficient extraction of nucleic acids from upper respiratory tract
      specimens (nasal washes and swabs). The performance of the nucleic acid
      extraction cards was directly compared to an existing standardized and automated
      platform for viral extraction from these types of specimens. The flowthrough card
      method improved the speed of nucleic acid purification and accommodated larger
      sample volumes in extraction of bacteriophage MS2 RNA from the various specimen
      matrices. The dynamic range and estimated sensitivity of the card extraction
      method for reverse transcriptase quantitative real-time PCR (RT-qPCR)-based
      detection approximate those of the standardized magnetic glass bead extraction
      method used in this study.

PMID- 21191052
TI  - Brain abscess caused by Phaeoacremonium parasiticum in an immunocompromised
      patient.
AB  - Phaeoacremonium parasiticum is an environmental fungus usually associated with
      subcutaneous infections. We report the first documented case of central nervous
      system involvement with brain abscess formation in a patient with chronic
      granulomatous disease and review the literature on Phaeoacremonium parasiticum
      infections.

PMID- 21191053
TI  - Rapid detection of Mycobacterium tuberculosis complex and rifampin resistance in
      smear-negative clinical samples by use of an integrated real-time PCR method.
AB  - Sixty-four of 85 (75.3%) smear-negative respiratory (n = 78) and nonrespiratory
      (n = 7) samples with positive cultures of Mycobacterium tuberculosis complex
      (MTC) were detected by the GeneXpert system using the Xpert MTB/RIF assay (GX).
      In addition, GX found rpoB mutations in all six of the rifampin-resistant strains
      detected. The test was negative in 20 culture-negative and 20 nontuberculous
      culture-positive samples (100% specificity). GX offers high potential for the
      diagnosis of tuberculosis due to its capacity for direct detection of MTC, its
      rapidity, and its simplicity.

PMID- 21191054
TI  - Pathogen-specific DNA enrichment does not increase sensitivity of PCR for
      diagnosis of invasive aspergillosis in neutropenic patients.
AB  - PCR assays designed for the diagnosis of invasive aspergillosis (IA) in high-risk
      patients have to detect minute amounts of target DNA to reach sufficient
      analytical sensitivity to be of clinical use. This prospective study assessed the
      use of a novel strategy for selective pathogen DNA enrichment for enhancing the
      performance of diagnostic PCR in a direct comparison with a highly sensitive in
      house quantitative PCR (qPCR) assay and the galactomannan enzyme-linked
      immunosorbent assay (ELISA). Surprisingly, and in contrast to experience with
      other patient groups, the novel protocol for selective pathogen DNA enrichment
      did not enhance but instead significantly impaired sensitivity. This could be
      explained by the small amounts of host DNA in the specimens, which were derived
      mostly from severely neutropenic patients. In the qPCR assay, positive samples
      required an average of 43.5 amplification cycles (range, 39.2 to 50) for
      detection in the in-house PCR. Repetitive testing of selected samples showed test
      positivity to be variable, most likely due to the small amounts of target DNA.
      Despite this, the in-house protocol proved helpful in the diagnosis of IA,
      detecting 2 out of 3 patients with probable IA and 10 out of 19 patients with
      possible IA. Our results underline the necessity for diagnostic PCR protocols
      that help diagnose IA to be highly sensitive and show that selective pathogen DNA
      enrichment using affinity purification may not be useful in severely neutropenic
      patients.

PMID- 21191055
TI  - Evaluation of the rapid MGIT TBc identification test for culture confirmation of
      Mycobacterium tuberculosis complex strain detection.
AB  - A culture confirmation test for the detection of Mycobacterium tuberculosis
      complex strains that uses a lateral-flow immunochromatographic assay to detect
      the MPB64 antigen, the MGIT TBc identification (TBc ID) test, has been developed.
      We evaluated the performance of the TBc ID test in the detection of the M.
      tuberculosis complex in 222 primary-positive liquid cultures. We compared these
      results to those of nucleic acid-based identification and conventional
      biochemical tests. The validity of the TBc ID test was determined, and all of the
      nontuberculous mycobacteria (NTM) and Nocardia species tested were found to be
      negative. The detection limit of the TBc ID test was 5 * 10(5) CFU/ml, and for
      IS6110 real-time PCR it was 5 CFU/ml. All of the M. tuberculosis and M. africanum
      cultures were found to be positive, while M. bovis and M. bovis BCG cultures were
      negative. With the exception of 1 contaminated culture, the 221 culture-positive
      isolates contained 171 (77.5%) M. tuberculosis isolates, 39 (17.6%) NTM species,
      and 11 (5.0%) unidentified species. Two culture-positive isolates harbored a 63
      bp deletion at position 196 of the mpb64 gene. The sensitivity, specificity,
      positive predictive values, and negative predictive values of the TBc ID test
      were 98.8, 100, 100, and 95.1%, respectively. Furthermore, the approximate
      turnaround time for real-time PCR was 4 h (including buffer and sample
      preparation), while for the TBc ID test it was less than 1 h. We suggest an
      algorithm for the primary identification of M. tuberculosis in liquid culture
      using the TBc ID test as an alternative to conventional subculture followed by
      identification using biochemical methods.

PMID- 21191056
TI  - Unapparent microsporidial infection among immunocompetent humans in the Czech
      Republic.
AB  - In the present population-based study, we determined the prevalences of the most
      common human-pathogenic microsporidia, Encephalitozoon spp. and Enterocytozoon
      bieneusi, in asymptomatic healthy people living in the Czech Republic. A total of
      382 males and females (ages, 1 to 84 years) living in the Czech Republic, of whom
      265 were Czech nationals and 117 were foreign students, were included in a study
      testing for the presence of microsporidia by use of coprology and molecular
      methods. Single-species infections with Enterocytozoon bieneusi or an
      Encephalitozoon sp. were detected for 9 and 136 individuals, respectively.
      Moreover, coinfections were detected for 14 individuals. Four genotypes of 3
      human-pathogenic Encephalitozoon spp. and 7 E. bieneusi genotypes, including 3
      novel genotypes, were detected. Some of these were reported in humans for the
      first time. The highest prevalence was recorded for individuals older than 50
      years and for loose, unformed stool samples. These findings clearly show that
      exposure to microsporidia is common among immunocompetent people and that
      microsporidiosis is not linked to any clinical manifestation in healthy
      populations.

PMID- 21191057
TI  - Incidence and epidemiology of Streptococcus pseudoporcinus in the genital tract.
AB  - Streptococcus pseudoporcinus, a beta-hemolytic microorganism first isolated from
      the female gastrourinary tract in 2006, cross-reacts with serogrouping kits for
      group B Streptococcus (GBS) and could be misidentified in the laboratory. The
      epidemiologic characteristics of this species have not been reported previously,
      but this organism is thought to be rare. Paired vaginal and rectal samples were
      collected from 663 nonpregnant women enrolled in a phase II clinical vaccine
      trial of a GBS type III capsular polysaccharide-protein conjugate vaccine, and
      isolates initially identified as S. pseudoporcinus were collected for further
      testing. A total of 120 isolates of S. pseudoporcinus were recovered from 36
      unique individuals with 5.4% of 663 women having this organism recovered at least
      once during follow-up. All of these isolates cross-reacted with a commercially
      available GBS serogrouping kit. Women colonized with isolates confirmed as S.
      pseudoporcinus by genotypic and phenotypic methodologies were compared to women
      who were not colonized to determine whether there were any significant factors
      associated with acquisition of S. pseudoporcinus. Acquisition of S.
      pseudoporcinus vaginally and/or rectally was 36 per 846.0 women-years of follow
      up for an annual incidence of 4 per 100 woman-years of follow-up. Acquisition of
      S. pseudoporcinus was independently associated with black women, being 30 to 40
      years of age, recent Trichomonas vaginalis infection, primary or recurrent
      genital herpes, having bacterial vaginosis by Nugent criteria, and having had two
      or more male sexual partners since the last visit. This study suggests that S.
      pseudoporcinus is not rare, especially among black women, and could be
      misidentified as GBS.

PMID- 21191058
TI  - Prevalence and risk factor analysis for methicillin-resistant Staphylococcus
      aureus nasal colonization in children attending child care centers.
AB  - Children attending child care centers (CCCs) are at increased risk for
      infections, including those caused by methicillin-resistant Staphylococcus aureus
      (MRSA). Nasal colonization often precedes infection, and MRSA colonization has
      been associated with increased infection risk. Community-associated MRSA (CA
      MRSA) has caused increased MRSA infections in the general population, including
      children. Little is known about the frequency of MRSA nasal colonization in young
      children, particularly in those attending CCCs where disease transmission is
      common. We sampled the nares of 1,163 children in 200 classrooms from 24 CCCs in
      North Carolina and Virginia to assess S. aureus colonization. MRSA strains were
      molecularly analyzed for staphylococcal cassette chromosome mec (SCCmec) type,
      Panton-Valentine leukocidin status, and multilocus sequence type. A case-control
      study was performed to identify risk factors for MRSA colonization. We found that
      18.1% children were colonized with S. aureus and 1.3% with MRSA. Molecular
      analysis of the MRSA strains identified 47% as CA-MRSA and 53% as health care
      associated MRSA (HA-MRSA). Although two centers had multiple children colonized
      with MRSA, genotyping indicated that no transmission had occurred within
      classrooms. The case-control study did not detect statistically significant risk
      factors for MRSA colonization. However, MRSA-colonized children were more likely
      to be nonwhite and to have increased exposure to antibiotics and skin infections
      in the home. Both CA-MRSA and HA-MRSA strains were found colonizing the nares of
      children attending CCCs. The low frequency of colonization observed highlights
      the need for a large multicenter study to determine risk factors for MRSA
      colonization and subsequent infection in this highly susceptible population.

PMID- 21191059
TI  - Klebsiella pneumoniae strains producing extended-spectrum beta-lactamases in
      Spain: microbiological and clinical features.
AB  - Extended-spectrum beta-lactamases (ESBL) of the CTX-M, SHV, and TEM families were
      recognized in 76 (67%), 31 (27%), and 6 (5%) isolates, respectively, among 162
      ESBL-producing Klebsiella pneumoniae (ESBL-Kp) strains obtained in a multicenter
      study in Spain. Predisposing factors for ESBL-Kp acquisition included invasive
      procedures, mechanical ventilation, and previous antimicrobial use.

PMID- 21191060
TI  - Simultaneous identification of mycobacterial isolates to the species level and
      determination of tuberculosis drug resistance by PCR followed by electrospray
      ionization mass spectrometry.
AB  - Mycobacterium tuberculosis that is resistant to both isoniazid (INH) and rifampin
      (RIF) is spreading. It has become a public health problem in part because the
      standard culture methods used to determine the appropriate treatment regimen for
      patients often take months following the presumptive diagnosis of tuberculosis.
      Furthermore, the misidentification of nontuberculosis mycobacteria (NTM) in
      patients presumably suffering from tuberculosis results in additional human and
      health care costs. The mechanisms of resistance for several drugs used to treat
      Mycobacterium tuberculosis are well understood and therefore should be amenable
      to determination by rapid molecular methods. We describe here the use of PCR
      followed by electrospray ionization mass spectrometry (PCR/ESI-MS) in an assay
      that simultaneously determines INH and RIF resistance in Mycobacterium
      tuberculosis and identifies and determines the species of NTMs. The assay panel
      included 16 primer pairs in eight multiplexed reactions and was validated using a
      collection of 1,340 DNA samples from cultured specimens collected in the New York
      City area, the Republic of Georgia, and South Africa. Compared with phenotypic
      data, the PCR/ESI-MS assay had 89.3% sensitivity and 95.8% specificity in the
      determination of INH resistance and 96.3% sensitivity and 98.6% specificity in
      the determination of RIF resistance. Based on a set of 264 previously
      characterized liquid culture specimens, the PCR/ESI-MS method had 97.0%
      sensitivity and 99.9% specificity for determination of NTM identity. The assay
      also provides information on ethambutol, fluoroquinolone, and diarylquinoline
      resistance and lineage-specific polymorphisms, to yield highly discriminative
      digital signatures potentially suitable for epidemiology tracking.

PMID- 21191062
TI  - Identification of endothelial cell junctional proteins and lymphocyte receptors
      involved in transendothelial migration of human effector memory CD4+ T cells.
AB  - Human effector memory (EM) CD4(+) T cells can rapidly transmigrate across an
      endothelial cell (EC) monolayer in response either to chemokine or to TCR
      activating signals displayed by human dermal microvascular EC under conditions of
      venular shear stress. We previously reported that the TCR-stimulated
      transendothelial migration (TEM) depends on fractalkine (CX3CL1), PECAM-1 (CD31),
      and ICAM-1 (CD54) expression by the EC, whereas chemokine-stimulated TEM does
      not. In this study, we further analyze these responses using blocking mAb and
      small interfering RNA knockdown to show that TCR-stimulated TEM depends on CD99
      on EC as well as on PECAM-1 and depends on nectin-2 (CD112) and poliovirus
      receptor (CD155) as well as EC ICAM-1. ICAM-1 is engaged by EM CD4(+) T cell LFA
      1 (CD11a/CD18) but not Mac-1 (CD11b/CD18); nectin-2 and poliovirus receptor are
      engaged by both DNAX accessory molecule-1 (CD226) and Tactile (CD96). EC
      junctional adhesion molecule-1 (JAM-1), an alternative ligand for LFA-1,
      contributes exclusively to chemokine-stimulated TEM and ICAM-2 appears to be
      uninvolved in either pathway. These data further define and further highlight the
      differences in the two pathways of EM CD4(+) T cell recruitment into sites of
      peripheral inflammation.

PMID- 21191061
TI  - Molecular epidemiology of hepatitis D virus infection among injecting drug users
      with and without human immunodeficiency virus infection in Taiwan.
AB  - An outbreak of human immunodeficiency virus (HIV) infection occurred among
      injecting drug users (IDU) in Taiwan between 2003 and 2006, when an extremely
      high prevalence of hepatitis C virus (HCV) infection was also detected. To
      determine whether clusters of hepatitis D virus (HDV) infection occurred in this
      outbreak, 4 groups of subjects were studied: group 1, HIV-infected IDU (n = 904);
      group 2, HIV-infected non-IDU (n = 880); group 3, HIV-uninfected IDU (n = 211);
      and group 4, HIV-uninfected non-IDU (n = 1,928). The seroprevalence of hepatitis
      B virus (HBV) was 19.8%, 18.4%, 17.1%, and 6.7%, and HDV seroprevalence among HBV
      carriers was 75.4%, 9.3%, 66.7%, and 2.3%, for groups 1, 2, 3, and 4,
      respectively. Ninety-nine of 151 (65.6%) HDV-seropositive IDU had HDV viremia: 5
      were infected with HDV genotype I, 41 with genotype II, 51 with genotype IV, and
      2 with genotypes II and IV. In the phylogenetic analysis, only one cluster of 4
      strains within the HDV genotype II was identified. Among patients with HCV
      viremia, a unique cluster within genotype 1a was observed; yet, patients within
      this cluster did not overlap with those observed in the HDV phylogenetic
      analysis. In summary, although IDU had a significantly higher HDV seroprevalence,
      molecular epidemiologic investigations did not support that HDV was introduced at
      the same time as HCV among IDU.

PMID- 21191063
TI  - T cell-intrinsic factors contribute to the differential ability of CD8+ T cells
      to rapidly secrete IFN-gamma in the absence of antigen.
AB  - A subset of CD44(hi)CD8(+) T cells isolated from C57BL/6/J (B6) mice, but not
      BALB/c/By/J (BALB/c) mice, rapidly secrete IFN-gamma within 16 h of infection
      with Listeria monocytogenes. This Ag-independent response requires the presence
      of both IL-12 and IL-18. Previous studies showed that dendritic cells from B6
      mice produced more Th1-type cytokines such as IL-12 than did those from BALB/c
      mice in response to L. monocytogenes infection. In this report, we demonstrate
      that the microenvironment in L. monocytogenes-infected BALB/c mice is sufficient
      to induce responsive B6 CD8(+) T cells to rapidly secrete IFN-gamma. Furthermore,
      BALB/c CD8(+) T cells did not rapidly secrete IFN-gamma even when they were
      exposed to high concentrations of IL-12 plus IL-18 in vitro. In the presence of
      IL-12 and IL-18, B6 CD44(hi)CD8(+) T cells upregulated expression of the receptor
      subunits for these cytokines more rapidly than did BALB/c T cells. In comparing
      particular subsets of memory phenotype CD8(+) T cells, we found that virtual
      memory cells, rather than true Ag-experienced cells, had the greatest level of
      impairment in BALB/c mice. These data suggest that the degree of cytokine-driven
      bystander activation of CD8(+) T cells that occurs during infection depends on
      both APCs and T cell-intrinsic properties that can vary among mouse strains.

PMID- 21191065
TI  - Lung cancer-derived galectin-1 mediates dendritic cell anergy through inhibitor
      of DNA binding 3/IL-10 signaling pathway.
AB  - Lung cancer, one of the leading causes of death worldwide, is often associated
      with a state of immune suppression, but the molecular and functional basis
      remains enigmatic. Evidence is provided in this paper supporting the role of lung
      cancer-derived soluble lectin, galectin-1, as a culprit in dendritic cell (DC)
      anergy. We have shown that galectin-1 is highly expressed in lung cancer cell
      lines, together with the serum and surgical samples from lung cancer patients.
      Functionally, lung cancer-derived galectin-1 has been shown to alter the
      phenotypes of monocyte-derived DCs (MdDCs) and impair alloreactive T cell
      response, concomitant with the increase of CD4(+)CD25(+)FOXP3(+) regulatory T
      cells. The regulatory effect of galectin-1 is mediated, in part, through its
      ability to induce, in an Id3 (inhibitor of DNA binding 3)-dependent manner, the
      expression of IL-10 in monocytes and MdDCs. This effect is inhibited by the
      addition of lactose, which normalizes the phenotypic and functional alterations
      seen in MdDCs. Of note, significant upregulation of IL-10 was seen in tumor
      infiltrating CD11c(+) DCs in human lung cancer samples. This was also noted in
      mice transplanted with lung cancer cells, but not in those receiving tumor cells
      with galectin-1 knockdown. Furthermore, a significant reduction was noted in lung
      cancer incidence and in the levels of IL-10-expressing, tumor-infiltrating DCs,
      in mice receiving galectin-1-silenced tumor cells. These results thus suggest
      that the galectin-1/IL-10 functional axis may be crucial in lung cancer-mediated
      immune suppression, and that galectin-1 may serve as a target in the development
      of lung cancer immunotherapy.

PMID- 21191064
TI  - Glycogen synthase kinase-3 is an early determinant in the differentiation of
      pathogenic Th17 cells.
AB  - CD4(+) T cells are critical for host defense but are also major drivers of immune
      mediated diseases. The classical view of Th1 and Th2 subtypes of CD4(+) T cells
      was recently revised by the identification of the Th17 lineage of CD4(+) T cells
      that produce IL-17, which have been found to be critical in the pathogenesis of
      autoimmune and other diseases. Mechanisms controlling the differentiation of Th17
      cells have been well described, but few feasible targets for therapeutically
      reducing Th17 cells are known. The generation of Th17 cells requires IL-6 and
      activation of STAT3. During polarization of CD4(+) T cells to Th17 cells, we
      found that inhibition of glycogen synthase kinase-3 (GSK3) blocked IL-6
      production, STAT3 activation, and polarization to Th17 cells. Polarization of
      CD4(+) T cells to Th17 cells increased by 10-fold the expression of GSK3beta
      protein levels in Th17 cells, whereas GSK3beta was unaltered in regulatory T
      cells. Diminishing GSK3 activity either pharmacologically or molecularly blocked
      Th17 cell production, and increasing GSK3 activity promoted polarization to Th17
      cells. In vivo inhibition of GSK3 in mice depleted constitutive Th17 cells in
      intestinal mucosa, blocked Th17 cell generation in the lung after Francisella
      tularensis infection, and inhibited the increase in spinal cord Th17 cells and
      disease symptoms in the experimental autoimmune encephalomyelitis mouse model of
      multiple sclerosis. These findings identify GSK3 as a critical mediator of Th17
      cell production and indicate that GSK3 inhibitors provide a potential therapeutic
      intervention to control Th17-mediated diseases.

PMID- 21191066
TI  - A human NK cell activation/inhibition threshold allows small changes in the
      target cell surface phenotype to dramatically alter susceptibility to NK cells.
AB  - NK cell activation is negatively regulated by the expression of target cell MHC
      class I molecules. We show that this relationship is nonlinear due to an NK cell
      activation/inhibition threshold. Ewing's sarcoma family tumor cell monolayers,
      which were highly susceptible to NK cells in vitro, developed a highly resistant
      phenotype when cultured as three-dimensional multicellular tumor spheroid
      structures. This suggested that tumor architecture is likely to influence the
      susceptibility to NK cells in vivo. Resistance of the multicellular tumor
      spheroid was associated with the increased expression of MHC class I molecules
      and greatly reduced NK cell activation, implying that a threshold of NK cell
      activation/inhibition had been crossed. Reducing MHC class I expression on
      Ewing's sarcoma family tumor monolayers did not alter their susceptibility to NK
      cells, whereas increased expression of MHC class I rendered them resistant and
      allowed the threshold point to be identified. This threshold, as defined by MHC
      class I expression, was predictive of the number of NK-resistant target cells
      within a population. A threshold permits modest changes in the target cell
      surface phenotype to profoundly alter the susceptibility to NK cells. Whereas
      this allows for the efficient detection of target cells, it also provides a route
      for pathogens and tumors to evade NK cell attack.

PMID- 21191067
TI  - Cutting edge: NLRC5-dependent activation of the inflammasome.
AB  - The nucleotide-binding domain leucine-rich repeat-containing proteins, NLRs, are
      intracellular sensors of pathogen-associated molecular patterns and damage
      associated molecular patterns. A subgroup of NLRs can form inflammasome
      complexes, which facilitate the maturation of procaspase 1 to caspase 1, leading
      to IL-1beta and IL-18 cleavage and secretion. NLRC5 is predominantly expressed in
      hematopoietic cells and has not been studied for inflammasome function. RNA
      interference-mediated knockdown of NLRC5 nearly eliminated caspase 1, IL-1beta,
      and IL-18 processing in response to bacterial infection, pathogen-associated
      molecular patterns, and damage-associated molecular patterns. This was confirmed
      in primary human monocytic cells. NLRC5, together with procaspase 1, pro-IL
      1beta, and the inflammasome adaptor ASC, reconstituted inflammasome activity that
      showed cooperativity with NLRP3. The range of pathogens that activate NLRC5
      inflammasome overlaps with those that activate NLRP3. Furthermore, NLRC5
      biochemically associates with NLRP3 in a nucleotide-binding domain-dependent but
      leucine-rich repeat-inhibitory fashion. These results invoke a model in which
      NLRC5 interacts with NLRP3 to cooperatively activate the inflammasome.

PMID- 21191068
TI  - A virus-like particle-based anti-nerve growth factor vaccine reduces inflammatory
      hyperalgesia: potential long-term therapy for chronic pain.
AB  - Chronic pain resulting from inflammatory and neuropathic disorders causes
      considerable economic and social burden. For a substantial proportion of
      patients, conventional drug treatments do not provide adequate pain relief.
      Consequently, novel approaches to pain management, involving alternative targets
      and new therapeutic modalities compatible with chronic use, are being sought.
      Nerve growth factor (NGF) is a major mediator of chronic pain. Clinical testing
      of NGF antagonists is ongoing, and clinical proof of concept has been established
      with a neutralizing mAb. Active immunization, with the goal of inducing
      therapeutically effective neutralizing autoreactive Abs, is recognized as a
      potential treatment option for chronic diseases. We have sought to determine if
      such a strategy could be applied to chronic pain by targeting NGF with a virus
      like particle (VLP)-based vaccine. A vaccine comprising recombinant murine NGF
      conjugated to VLPs from the bacteriophage Qbeta (NGFQbeta) was produced.
      Immunization of mice with NGFQbeta induced anti-NGF-specific IgG Abs capable of
      neutralizing NGF. Titers could be sustained over 1 y by periodic immunization but
      declined in the absence of boosting. Vaccination with NGFQbeta substantially
      reduced hyperalgesia in collagen-induced arthritis or postinjection of zymosan A,
      two models of inflammatory pain. Long-term NGFQbeta immunization did not change
      sensory or sympathetic innervation patterns or induce cholinergic deficits in the
      forebrain, nor did it interfere with blood-brain barrier integrity. Thus,
      autovaccination targeting NGF using a VLP-based approach may represent a novel
      modality for the treatment of chronic pain.

PMID- 21191070
TI  - Epigenetic reduction in invariant NKT cells following in utero vitamin D
      deficiency in mice.
AB  - Vitamin D status changes with season, but the effect of these changes on immune
      function is not clear. In this study, we show that in utero vitamin D deficiency
      in mice results in a significant reduction in invariant NKT (iNKT) cell numbers
      that could not be corrected by later intervention with vitamin D or 1,25
      dihydroxy vitamin D(3) (active form of the vitamin). Furthermore, this was
      intrinsic to hematopoietic cells, as vitamin D-deficient bone marrow is
      specifically defective in generating iNKT cells in wild-type recipients. This
      vitamin D deficiency-induced reduction in iNKT cells is due to increased
      apoptosis of early iNKT cell precursors in the thymus. Whereas both the vitamin D
      receptor and vitamin D regulate iNKT cells, the vitamin D receptor is required
      for both iNKT cell function and number, and vitamin D (the ligand) only controls
      the number of iNKT cells. Given the importance of proper iNKT cell function in
      health and disease, this prenatal requirement for vitamin D suggests that in
      humans, the amount of vitamin D available in the environment during prenatal
      development may dictate the number of iNKT cells and potential risk of
      autoimmunity.

PMID- 21191071
TI  - EBV lytic-phase protein BGLF5 contributes to TLR9 downregulation during
      productive infection.
AB  - Viruses use a wide range of strategies to modulate the host immune response. The
      human gammaherpesvirus EBV, causative agent of infectious mononucleosis and
      several malignant tumors, encodes proteins that subvert immune responses, notably
      those mediated by T cells. Less is known about EBV interference with innate
      immunity, more specifically at the level of TLR-mediated pathogen recognition.
      The viral dsDNA sensor TLR9 is expressed on B cells, a natural target of EBV
      infection. Here, we show that EBV particles trigger innate immune signaling
      pathways through TLR9. Furthermore, using an in vitro system for productive EBV
      infection, it has now been possible to compare the expression of TLRs by EBV(-)
      and EBV(+) human B cells during the latent and lytic phases of infection. Several
      TLRs were found to be differentially expressed either in latently EBV-infected
      cells or after induction of the lytic cycle. In particular, TLR9 expression was
      profoundly decreased at both the RNA and protein levels during productive EBV
      infection. We identified the EBV lytic-phase protein BGLF5 as a protein that
      contributes to downregulating TLR9 levels through RNA degradation. Reducing the
      levels of a pattern-recognition receptor capable of sensing the presence of EBV
      provides a mechanism by which the virus could obstruct host innate antiviral
      responses.

PMID- 21191069
TI  - Diverse endogenous antigens for mouse NKT cells: self-antigens that are not
      glycosphingolipids.
AB  - NKT cells with an invariant Ag receptor (iNKT cells) represent a highly conserved
      and unique subset of T lymphocytes having properties of innate and adaptive
      immune cells. They have been reported to regulate a variety of immune responses,
      including the response to cancers and the development of autoimmunity. The
      development and activation of iNKT cells is dependent on self-Ags presented by
      the CD1d Ag-presenting molecule. It is widely believed that these self-Ags are
      glycosphingolipids (GSLs), molecules that contain ceramide as the lipid backbone.
      In this study, we used a variety of methods to show that mammalian Ags for mouse
      iNKT cells need not be GSLs, including the use of cell lines deficient in GSL
      biosynthesis and an inhibitor of GSL biosynthesis. Presentation of these Ags
      required the expression of CD1d molecules that could traffic to late endosomes,
      the site where self-Ag is acquired. Extracts of APCs contain a self-Ag that could
      stimulate iNKT cells when added to plates coated with soluble, rCD1d molecules.
      The Ag(s) in these extracts are resistant to sphingolipid-specific hydrolase
      digestion, consistent with the results using live APCs. Lyosphosphatidylcholine,
      a potential self-Ag that activated human iNKT cell lines, did not activate mouse
      iNKT cell hybridomas. Our data indicate that there may be more than one type of
      self-Ag for iNKT cells, that the self-Ags comparing mouse and human may not be
      conserved, and that the search to identify these molecules should not be confined
      to GSLs.

PMID- 21191072
TI  - Autophagy regulates endoplasmic reticulum homeostasis and calcium mobilization in
      T lymphocytes.
AB  - Macroautophagy (hereafter referred to as autophagy) is an evolutionarily
      conserved intracellular bulk degradation pathway that plays critical roles in
      eliminating intracellular pathogens, presenting endogenous Ags, and regulating T
      lymphocyte survival and proliferation. In this study, we have investigated the
      role of autophagy in regulating the endoplasmic reticulum (ER) compartment in T
      lymphocytes. We found that ER content is expanded in mature autophagy-related
      protein (Atg) 7-deficient T lymphocytes. Atg7-deficient T cells stimulated
      through the TCR display impaired influx, but not efflux, of calcium, and ER
      calcium stores are increased in Atg7-deficient T cells. Treatment with the ER
      sarco/ER Ca(2+)-ATPase pump inhibitor thapsigargin rescues the calcium influx
      defect in Atg7-deficient T lymphocytes, suggesting that this impairment is caused
      by an intrinsic defect in ER. Furthermore, we found that the stimulation-induced
      redistribution of stromal interaction molecule-1, a critical event for the store
      operated Ca(2+) release-activated Ca(2+) channel opening, is impaired in Atg7
      deficient T cells. Together, these findings indicate that the expanded ER
      compartment in Atg7-deficient T cells contains increased calcium stores, and the
      inability of these stores to be depleted causes defective calcium influx in these
      cells. Our results demonstrate that autophagy plays an important role in
      maintaining ER and calcium homeostasis in T lymphocytes.

PMID- 21191073
TI  - Senescent CD14+CD16+ monocytes exhibit proinflammatory and proatherosclerotic
      activity.
AB  - In elderly subjects and in patients with chronic inflammatory diseases, there is
      an increased subset of monocytes with a CD14(+)CD16(+) phenotype, whose origin
      and functional relevance has not been well characterized. In this study, we
      determined whether prolonged survival of human CD14(++)CD16(-) monocytes promotes
      the emergence of senescent cells, and we analyzed their molecular phenotypic and
      functional characteristics. We used an in vitro model to prolong the life span of
      healthy monocytes. We determined cell senescence, intracellular cytokine
      expression, ability to interact with endothelial cells, and APC activity.
      CD14(+)CD16(+) monocytes were senescent cells with shortened telomeres (215 +/-
      37 relative telomere length) versus CD14(++)CD16(-) cells (339 +/- 44 relative
      telomere length; p < 0.05) and increased expression of beta-galactosidase (86.4
      +/- 16.4% versus 10.3 +/- 7.5%, respectively; p = 0.002). CD14(+)CD16(+)
      monocytes exhibited features of activated cells that included expression of
      CD209, release of cytokines in response to low-intensity stimulus, and increased
      capacity to sustain lymphocyte proliferation. Finally, compared with
      CD14(++)CD16(-) cells, CD14(+)CD16(+) monocytes showed elevated expression of
      chemokine receptors and increased adhesion to endothelial cells (19.6 +/- 8.1%
      versus 5.3 +/- 4.1%; p = 0.033). In summary, our data indicated that the
      senescent CD14(+)CD16(+) monocytes are activated cells, with increased
      inflammatory activity and ability to interact with endothelial cells. Therefore,
      accumulation of senescent monocytes may explain, in part, the development of
      chronic inflammation and atherosclerosis in elderly subjects and in patients with
      chronic inflammatory diseases.

PMID- 21191075
TI  - CD1d-restricted IFN-gamma-secreting NKT cells promote immune complex-induced
      acute lung injury by regulating macrophage-inflammatory protein-1alpha production
      and activation of macrophages and dendritic cells.
AB  - Immune complex-induced acute lung injury (IC-ALI) has been implicated in various
      pulmonary disease states. However, the role of NKT cells in IC-ALI remains
      unknown. Therefore, we explored NKT cell functions in IC-ALI using chicken egg
      albumin and anti-chicken egg albumin IgG. The bronchoalveolar lavage fluid of
      CD1d(-/-) and Jalpha18(-/-) mice contained few Ly6G(+)CD11b(+) granulocytes,
      whereas levels in B6 mice were greater and were increased further by alpha
      galactosyl ceramide. IFN-gamma and MIP-1alpha production in the lungs was greater
      in B6 than CD1d(-/-) mice. Adoptive transfer of wild type (WT) but not IFN-gamma
      , MIP-1alpha-, or FcgammaR-deficient NKT cells into CD1d(-/-) mice caused
      recruitment of inflammatory cells to the lungs. Moreover, adoptive transfer of
      IFN-gammaR-deficient NKT cells enhanced MIP-1alpha production and cell
      recruitment in the lungs of CD1d(-/-) or CD1d(-/-)IFN-gamma(-/-) mice, but to a
      lesser extent than WT NKT cells. This suggests that IFN-gamma-producing NKT cells
      enhance MIP-1alpha production in both an autocrine and a paracrine manner. IFN
      gamma-deficient NKT cells induced less IL-1beta and TNF-alpha production by
      alveolar macrophages and dendritic cells in CD1d(-/-) mice than did WT NKT cells.
      Taken together, these data suggest that CD1d-restricted IFN-gamma-producing NKT
      cells promote IC-ALI by producing MIP-1alpha and enhancing proinflammatory
      cytokine production by alveolar macrophages and dendritic cells.

PMID- 21191074
TI  - IL-1alpha modulates neutrophil recruitment in chronic inflammation induced by
      hydrocarbon oil.
AB  - Exposure to naturally occurring hydrocarbon oils is associated with the
      development of chronic inflammation and a wide spectrum of pathological findings
      in humans and animal models. The mechanism underlying the unremitting
      inflammatory response to hydrocarbons remains largely unclear. The medium-length
      alkane 2,6,10,14 tetramethylpentadecane (also known as pristane) is a hydrocarbon
      that potently elicits chronic peritonitis characterized by persistent
      infiltration of neutrophils and monocytes. In this study, we reveal the essential
      role of IL-1alpha in sustaining the chronic recruitment of neutrophils following
      2,6,10,14 tetramethylpentadecane treatment. IL-1alpha and IL-1R signaling promote
      the migration of neutrophils to the peritoneal cavity in a CXCR2-dependent
      manner. This mechanism is at least partially dependent on the production of the
      neutrophil chemoattractant CXCL5. Moreover, although chronic infiltration of
      inflammatory monocytes is dependent on a different pathway requiring TLR-7, type
      I IFN receptor, and CCR2, the adaptor molecules MyD88, IL-1R-associated kinase
      (IRAK)-4, IRAK-1, and IRAK-2 are shared in regulating the recruitment of both
      monocytes and neutrophils. Taken together, our findings uncover an IL-1alpha
      dependent mechanism of neutrophil recruitment in hydrocarbon-induced peritonitis
      and illustrate the interactions of innate immune pathways in chronic
      inflammation.

PMID- 21191076
TI  - Safety and immunogenicity of coadministering a combined meningococcal serogroup C
      and Haemophilus influenzae type b conjugate vaccine with 7-valent pneumococcal
      conjugate vaccine and measles, mumps, and rubella vaccine at 12 months of age.
AB  - The coadministration of the combined meningococcal serogroup C conjugate
      (MCC)/Haemophilus influenzae type b (Hib) vaccine with pneumococcal conjugate
      vaccine (PCV7) and measles, mumps, and rubella (MMR) vaccine at 12 months of age
      was investigated to assess the safety and immunogenicity of this regimen compared
      with separate administration of the conjugate vaccines. Children were randomized
      to receive MCC/Hib vaccine alone followed 1 month later by PCV7 with MMR vaccine
      or to receive all three vaccines concomitantly. Immunogenicity endpoints were MCC
      serum bactericidal antibody (SBA) titers of >=8, Hib-polyribosylribitol phosphate
      (PRP) IgG antibody concentrations of >=0.15 MUg/ml, PCV serotype-specific IgG
      concentrations of >=0.35 MUg/ml, measles and mumps IgG concentrations of >120
      arbitrary units (AU)/ml, and rubella IgG concentrations of >=11 AU/ml. For safety
      assessment, the proportions of children with erythema, swelling, or tenderness at
      site of injection or fever or other systemic symptoms for 7 days after
      immunization were compared between regimens. No adverse consequences for either
      safety or immunogenicity were demonstrated when MCC/Hib vaccine was given
      concomitantly with PCV and MMR vaccine at 12 months of age or separately at 12
      and 13 months of age. Any small differences in immunogenicity were largely in the
      direction of a higher response when all three vaccines were given concomitantly.
      For systemic symptoms, there was no evidence of an additive effect; rather, any
      differences between schedules showed benefit from the concomitant administration
      of all three vaccines, such as lower overall proportions with postvaccination
      fevers. The United Kingdom infant immunization schedule now recommends that these
      three vaccines may be offered at one visit at between 12 and 13 months of age.

PMID- 21191077
TI  - Evaluation of four commercial systems for the diagnosis of Epstein-Barr virus
      primary infections.
AB  - To compare the performance of four diagnostic commercial systems for Epstein-Barr
      virus (EBV) serology (for IgM and IgG virus capsid antigen [VCA] and EBV nuclear
      antigen [EBNA] antibodies), a collection of 125 samples from clinically suspected
      infectious mononucleosis cases was studied. Indirect immunofluorescence (IIF) for
      VCA IgM and IgG antibodies and anticomplement immunofluorescence for EBNA
      antibodies (Meridian Bioscience Inc.) were used as reference methods. By these
      methods, the cases were classified EBV primary infection (presence of IgM to VCA
      or IgG to VCA in the absence of EBNA antibodies; n = 82), EBV past infection
      (presence of VCA IgG and EBNA antibodies in the absence of VCA IgM; n = 26), or
      no infection (negative for the three markers; n = 17). The following systems were
      tested: two chemiluminescent immunoassays (CLIAs; the Liason [CLIA-L; DiaSorin]
      and the Immulite 2000 [CLIA-I; Siemens]), immunofiltration (IF; All.Diag), and an
      enzyme-linked immunosorbent assay (ELISA; DiaSorin). In the IgM assays,
      sensitivities ranged from 67.1% (ELISA) to 92.2% (CLIA-L) and specificities
      ranged from 93.8% (CLIA-L) to 100% (IF). In the VCA IgG assays, sensitivities
      varied from 79.4% (IF) to 94.4% (CLIA-I) and specificities varied from 94.4% (IF
      and CLIA-L) to 100% (CLIA-I and ELISA). In EBNA assays, sensitivities ranged from
      78.1% (IF) to 93.8% (CLIA-I) and specificities ranged from 32.3% (CLIA-L) to
      91.4% (IF). In relation to EBV profiles, the corresponding figures for
      sensitivity (in detecting primary infection) for IF, CLIA-L, CLIA-I, and ELISA
      were 92.7%, 93.8%, 89%, and 89.6%, respectively, and those for specificity (to
      exclude primary recent infection) were 90.7%, 94.6%, 97.7%, and 95.2%,
      respectively. Although there were limitations in some individual markers,
      especially CLIA-L for EBNA IgG, the systems evaluated appear to be useful for
      diagnosis of EBV infection.

PMID- 21191079
TI  - A translational research evaluation of the Stay Active and Independent for Life
      (SAIL) community-based fall prevention exercise and education program.
AB  - Falls in older adults are the leading cause of injury hospitalizations and
      fatalities in the United States; primary risk factors are muscle weakness,
      impaired mobility, and balance deficits. This article describes the 12-month
      translational research evaluation of the Stay Active and Independent for Life
      (SAIL) community-based public health, public domain fall prevention exercise and
      education program. Recruitment reached the target goal by 154%; 331 adults (mean
      age = 74.6) attended more than one class (mean classes attended = 24.8, SD =
      26.6, range = 1-120) at nine community sites in one county in the 12-month
      period; 173 completed health and demographic forms, 132 completed program
      surveys, and 91 completed baseline and follow-up physical function tests.
      Physical function test results showed significant improvements in strength,
      balance, and mobility in those who were below normal limits at baseline, and in
      those who attended classes twice a week or more for more than 2 months. Survey
      results found that 93% of respondents reported improved performance of daily
      activities; 92% reported improved strength, balance, fitness, or flexibility; and
      80% found the SAIL information guide education component helpful.

PMID- 21191080
TI  - College mentors: a view from the inside of an intervention to promote health
      behaviors and prevent obesity among low-income, urban, African American
      adolescents.
AB  - This article examined the views of college mentors who administered Challenge!-a
      home- and community-based health promotion/overweight prevention intervention
      that effectively reduced the progression to overweight among African American
      adolescents. In-depth qualitative interviews among 17 mentors (81%) conducted 1
      year following the intervention yielded four primary findings: (a) the importance
      of a strong mentor-mentee relationship often extending beyond the issues of diet
      and physical activity, (b) concern at the adversities the adolescents faced
      (e.g., poverty and household instability); (c) the personal impact of the
      mentoring process on the mentors' own dietary and physical activity behavior and
      career choices; and (d) recommendations regarding subsequent mentoring programs.
      In summary, college students are a valuable resource as mentors for low-income,
      African American adolescents and provide insights into the success of health
      promotion/overweight prevention interventions.

PMID- 21191078
TI  - Decreased serum antibody responses to recombinant pneumocystis antigens in HIV
      infected and uninfected current smokers.
AB  - Serologic studies can provide important insights into the epidemiology and
      transmission of Pneumocystis jirovecii. Exposure to P. jirovecii can be assessed
      by serum antibody responses to recombinant antigens from the major surface
      glycoprotein (MsgC), although factors that influence the magnitude of the
      antibody response are incompletely understood. We determined the magnitudes of
      antibody responses to P. jirovecii in comparison to adenovirus and respiratory
      syncytial virus (RSV) in HIV-infected and uninfected patients and identified
      predictors associated with the magnitude of the response. We performed a cross
      sectional analysis using serum samples and data from 153 HIV-positive and 92 HIV
      negative subjects enrolled in a feasibility study of the Veterans Aging Cohort 5
      Site Study (VACS 5). Antibodies were measured using an enzyme-linked
      immunosorbent assay (ELISA). Independent predictors of antibody responses were
      determined using multivariate Tobit regression models. The results showed that
      serum antibody responses to P. jirovecii MsgC fragments were significantly and
      independently decreased in current smokers. Antibodies to P. jirovecii also
      tended to be lower with chronic obstructive pulmonary disease (COPD), hazardous
      alcohol use, injection drug use, and HIV infection, although these results were
      not statistically significant. These results were specific to P. jirovecii and
      did not correlate with adenovirus. Antibody responses to RSV were in the inverse
      direction. Thus, current smoking was independently associated with decreased P.
      jirovecii antibody responses. Whether smoking exerts an immunosuppressive effect
      that affects the P. jirovecii antibody response, colonization, or subsequent risk
      for disease is unclear; prospective, longitudinal studies are needed to evaluate
      these findings further.

PMID- 21191081
TI  - An empirical study on outpatients' health education needs and the effectiveness
      of e-learning.
AB  - Health education is an important component in disease management. This study
      sought to understand outpatients' health education needs and explored the
      effectiveness of e-learning applications. A cross-section of 281 outpatients was
      surveyed over 2 months. First, the concept of health education and the
      application of e-learning technology were introduced. Second, outpatients were
      interviewed to learn about their perceptions, experiences, and health education
      needs (such as the perceptions of the importance of health education, the
      experience of received health education and, in their opinion, the best approach
      to health education). Finally, their willingness to use an e-learning technology
      and their satisfaction with it were investigated. It was found that gender, age,
      and level of education have a significant influence on patients' health education
      needs. Only 29.5% of outpatients felt satisfied with the traditional learning
      modalities. Most outpatients (72.2%) gave positive feedback about e-learning for
      health education. It can be concluded that there are different needs among a
      diverse patient population. Although some still favor health education sessions,
      TV programs, or posters as their source of learning, e-learning, as this study
      suggested, is an excellent approach to the promotion of outpatients' health.

PMID- 21191082
TI  - Knowledge of antioxidants and breast cancer risk among women attending breast
      cancer risk assessment clinics.
AB  - This qualitative study used semistructured interviews to examine the accuracy of
      knowledge concerning antioxidants and health among a convenience sample of 79
      women attending a breast cancer risk assessment clinic. Despite a high level of
      familiarity (98%) with the word antioxidant, few participants could name more
      than one of these compounds and most relied on print media (41.6%) and radio/TV
      (22.2%) for antioxidant information. Thematic content analysis revealed
      participants' beliefs that antioxidants were strongly linked to reduced breast
      cancer risk and improved health. They described antioxidant functions that take
      place before (e.g., "Prevention . . . a best defense mechanism" and "To boost
      strength and good health") or after (e.g., "Fights diseases, free radicals, and
      cancer," "Acts as a cleanser or purifier," and "Undoes the harm that I am
      consciously or unconsciously doing to my body") a health threat. Participants'
      understandings of the links between antioxidant intake and breast cancer risk did
      not accurately reflect the scientific evidence. This large priority population
      group needs tailored, evidence-based nutrition communications to address
      inaccurate understandings about antioxidant intake and breast cancer risk.

PMID- 21191083
TI  - Metabolism of gambogic acid in rats: a rare intestinal metabolic pathway
      responsible for its final disposition.
AB  - Gambogic acid (GA) is a promising natural anticancer candidate. Although the
      anticancer activity of GA has been well demonstrated, information regarding the
      metabolic fate of GA is limited. Previous studies suggested that GA is mainly
      excreted into intestinal tract in rats through bile after intravenous
      administration, whereas only traces appeared in the feces, suggesting that GA is
      metabolized extensively in the intestine. However, there has been no report about
      the intestinal metabolism of GA either in animals or humans. In this study, large
      amounts of two sulfonic acid metabolites of GA were found in the feces samples of
      rats after intravenous administration, and their structures were identified as 10
      alpha sulfonic acid GA and 10-beta sulfonic acid GA by comparison of the
      retention times and spectral data with those of synthesized reference substances
      using liquid chromatography-diode array detector-tandem mass spectrometry. This
      rare intestinal metabolic pathway mainly involves Michael addition of the sulfite
      ion to the 9,10 carbon-carbon double bond of alpha,beta-unsaturated ketone. In
      addition, a more detailed metabolic profile in rats is proposed, according to the
      results of in vitro and in vivo studies. It was found that GA can be metabolized
      by a variety of routes, including monooxidation, hydration, glutathionylation,
      glucuronidation, and glucosidation in the liver of rats. These findings provide
      information on the major metabolic soft spot of GA in the intestine and liver of
      rats, which is not only useful in the future human metabolic study of this
      compound but also of value in the metabolic studies of GA analogs.

PMID- 21191084
TI  - Completely isolated? Health information seeking among social isolates.
AB  - To better target messages it is important to determine where people seek their
      health information. Interpersonal networks are a common way most people gather
      health information, but some people have limited networks. Using data from the
      2004 General Social Survey (N=984), we compared social isolates and nonisolates
      in their health information-seeking behaviors. Results indicate that those with
      limited social networks are less likely to use interpersonal communication to
      seek health information and are also less likely to use mediated channels. The
      results suggest that isolates may also be suffering from a health knowledge gap.

PMID- 21191085
TI  - Older adults' perceptions of physical activity and cognitive health: implications
      for health communication.
AB  - Messages promoting physical activity (PA) to maintain cognitive health (CH) may
      increase PA and enhance CH among older persons. This study examined older adults'
      perceptions of PA and CH. We conducted 10 focus groups with irregularly active
      older Black and White women and men (N = 55), ages 65 to 74 in South Carolina.
      Constant comparison methods compared themes by gender and race/ethnicity groups.
      Most participants perceived cognitive decline as a severe threat, and they were
      primarily concerned about losing their independence. Most reported feeling
      susceptible to cognitive decline. Although most recognized the link between PA
      and CH, several White men said the association was not clear. Participants
      recommended a wide range of PA amounts needed to achieve CH benefits. Many
      suggested that evidence of PA benefits for CH would enhance message credibility.
      Participants suggested messages be paired with social support to increase PA.
      Results suggest a need for evidence-based, credible communication promoting PA
      and CH.

PMID- 21191086
TI  - Neisseria meningitidis capsular polysaccharides induce inflammatory responses via
      TLR2 and TLR4-MD-2.
AB  - CPS are major virulence factors in infections caused by Neisseria meningitidis
      and form the basis for meningococcal serogroup designation and protective
      meningococcal vaccines. CPS polymers are anchored in the meningococcal outer
      membrane through a 1,2-diacylglycerol moiety, but the innate immunostimulatory
      activity of CPS is largely unexplored. Well-established human and murine
      macrophage cell lines and HEK/TLR stably transfected cells were stimulated with
      CPS, purified from an endotoxin-deficient meningococcal serogroup B NMB-lpxA
      mutant. CPS induced inflammatory responses via TLR2- and TLR4-MD-2. Meningococcal
      CPS induced a dose-dependent release of cytokines (TNF-alpha, IL-6, IL-8, and
      CXCL10) and NO from human and murine macrophages, respectively. CPS induced IL-8
      release from HEK cells stably transfected with TLR2/6, TLR2, TLR2/CD14, and
      TLR4/MD-2/CD14 but not HEK cells alone. mAb to TLR2 but not an isotype control
      antibody blocked CPS-induced IL-8 release from HEK-TLR2/6-transfected cells. A
      significant reduction in TNF-alpha and IL-8 release was seen when THP-1- and HEK
      TLR4/MD-2-CD14- but not HEK-TLR2- or HEK-TLR2/6-transfected cells were stimulated
      with CPS in the presence of Eritoran (E5564), a lipid A antagonist that binds to
      MD-2, and a similar reduction in NO and TNF-alpha release was also seen in RAW
      264.7 cells in the presence of Eritoran. CD14 and LBP enhanced CPS bioactivity,
      and NF-kappaB was, as anticipated, the major signaling pathway. Thus, these data
      suggest that innate immune recognition of meningococcal CPS by macrophages can
      occur via TLR2- and TLR4-MD-2 pathways.

PMID- 21191087
TI  - Determinants of synonymous and nonsynonymous variability in three species of
      Drosophila.
AB  - We estimated the intensity of selection on preferred codons in Drosophila
      pseudoobscura and D. miranda at X-linked and autosomal loci, using a published
      data set on sequence variability at 67 loci, by means of an improved method that
      takes account of demographic effects. We found evidence for stronger selection at
      X-linked loci, consistent with their higher levels of codon usage bias. The
      estimates of the strength of selection and mutational bias in favor of
      unpreferred codons were similar to those found in other species, after taking
      into account the fact that D. pseudoobscura showed evidence for a recent
      expansion in population size. We examined correlates of synonymous and
      nonsynonymous diversity in these species and found no evidence for effects of
      recurrent selective sweeps on nonsynonymous mutations, which is probably because
      this set of genes have much higher than average levels of selective constraints.
      There was evidence for correlated effects of levels of selective constraints on
      protein sequences and on codon usage, as expected under models of selection for
      translational accuracy. Our analysis of a published data set on D. melanogaster
      provided evidence for the effects of selective sweeps of nonsynonymous mutations
      on linked synonymous diversity, but only in the subset of loci that experienced
      the highest rates of nonsynonymous substitutions (about one-quarter of the total)
      and not at more slowly evolving loci. Our correlational analysis of this data set
      suggested that both selective constraints on protein sequences and recurrent
      selective sweeps affect the overall level of codon usage.

PMID- 21191088
TI  - Dopaminergic neurons of system x(c)--deficient mice are highly protected against
      6-hydroxydopamine-induced toxicity.
AB  - Malfunctioning of system x(c)(-), responsible for exchanging intracellular
      glutamate for extracellular cystine, can cause oxidative stress and
      excitotoxicity, both important phenomena in the pathogenesis of Parkinson's
      disease (PD). We used mice lacking xCT (xCT(-/-) mice), the specific subunit of
      system x(c)(-), to investigate the involvement of this antiporter in PD. Although
      cystine that is imported via system x(c)(-) is reduced to cysteine, the rate
      limiting substrate in the synthesis of glutathione, deletion of xCT did not
      result in decreased glutathione levels in striatum. Accordingly, no signs of
      increased oxidative stress could be observed in striatum or substantia nigra of
      xCT(-/-) mice. In sharp contrast to expectations, xCT(-/-) mice were less
      susceptible to 6-hydroxydopamine (6-OHDA)-induced neurodegeneration in the
      substantia nigra pars compacta compared to their age-matched wild-type
      littermates. This reduced sensitivity to a PD-inducing toxin might be related to
      the decrease of 70% in striatal extracellular glutamate levels that was observed
      in mice lacking xCT. The current data point toward system x(c)(-) as a possible
      target for the development of new pharmacotherapies for the treatment of PD and
      emphasize the need to continue the search for specific ligands for system x(c)(
      ).

PMID- 21191089
TI  - Interleukin-1alpha is a regulator of the blood-testis barrier.
AB  - Throughout spermatogenesis, the Sertoli cell blood-testis barrier (BTB) is
      strictly regulated by cytokines, which mediate its timely restructuring, thereby
      allowing spermatocytes to enter the adluminal compartment of the seminiferous
      epithelium for development into spermatozoa. The aim herein was to investigate
      whether germ cells play a role in BTB restructuring via the action of interleukin
      1alpha (IL-1alpha) since germ cells are known to control Sertoli cell production
      of this cytokine, and if yes, how these effects are mediated. When Sertoli cells
      were isolated from Sprague-Dawley rats and plated at high density, IL-1alpha (100
      pg/ml) was shown to "open" the Sertoli cell barrier when its integrity was
      assessed by transepithelial electrical resistance measurements. Further
      investigation of Sertoli cells treated with IL-1alpha revealed striking changes
      in the cellular distribution of actin filaments when compared to untreated cells.
      These effects at the Sertoli cell barrier were mediated, in part, by epidermal
      growth factor receptor pathway substrate 8 (Eps8; an actin bundling and barbed
      end capping protein) and actin-related protein 3 (Arp3; a component of the actin
      nucleation machinery). As important, an increase in the kinetics of occludin
      internalization but a decrease in its rate of degradation was noted following IL
      1alpha treatment. These results indicate that IL-1alpha is a critical regulator
      of BTB dynamics.

PMID- 21191090
TI  - GIRK channel-mediated inhibition of melanin-concentrating hormone neurons by
      nociceptin/orphanin FQ.
AB  - Targeting the melanin-concentrating hormone (MCH) system has been suggested as a
      potential treatment for obesity, anxiety disorders, as well as addiction. Despite
      the therapeutic potential of MCH agonists and antagonists, the endogenous factors
      regulating MCH activity, in particular those implicated in anxiety and reward,
      are ill-defined. The present study investigated the cellular effects of
      nociceptin/orphanin FQ (N/OFQ), an endogenous opioid with anxiolytic and
      antireward properties, on MCH neurons. We found that N/OFQ induced a
      concentration-dependent reversible outward current in MCH neurons (EC(50) = 50.7
      nM), an effect that was blocked by the competitive antagonist of the nociceptin
      opioid peptide (NOP) receptor UFP-101. N/OFQ-induced outward currents persisted
      in TTX, reversed near the potassium equilibrium potential, and displayed inward
      rectification, suggesting direct postsynaptic potassium channel activation.
      Tertiapin-Q completely abolished the N/OFQ effect, whereas glibenclamide did not,
      implicating protein G-dependent inwardly rectifying potassium (GIRK) and not ATP
      sensitive potassium (K(ATP)) channels as the effector ion channel. The N/OFQ
      induced outward current desensitized during repeated applications and occluded
      the inhibitory effect of dynorphin, suggesting that dynorphin and N/OFQ activate
      the same pathway. N/OFQ also reversibly inhibited voltage-gated calcium currents
      in MCH neurons. In conclusion, our study indicates N/OFQ as a robust endogenous
      regulator of MCH neurons, which may play a role in anxiety and drug addiction.

PMID- 21191091
TI  - The dynamics of somatic input processing in spinal motoneurons in vivo.
AB  - Uncovering how motoneurons utilize their voltage-sensitive conductances to
      systematically respond to a variety of inputs is paramount to understanding
      synaptic integration. In this study, we examine the input dynamics and frequency
      dependent characteristics of active conductances in motoneurons as viewed from
      the soma in the decerebrate cat. We evaluated the somatic response of the
      motoneuron by superimposing a voltage sinus sweep (a sine wave in which frequency
      increases with time, which is often referred to as a zap or chirp) at a subset of
      membrane holding potentials during discontinuous, single-electrode, somatic
      voltage-clamp. Results from both experimental and modeling data indicate that
      ionic conductances can respond to a wide variety of input dynamics. Notably, it
      appears that there is a divergence between low input conductance type S and high
      input conductance type FF motoneurons in their response to input frequency. Type
      S motoneurons generate a larger response to lower frequency input dynamics
      (compared with their response to higher frequencies), whereas type FF generate a
      larger response to higher input frequency dynamics. Functionally, these results
      may indicate that motoneurons on the lower end of the motor pool (i.e., recruited
      first) may favor steady inputs, whereas motoneurons at the higher end (i.e.,
      recruited later) may favor input transients in producing action potentials.

PMID- 21191092
TI  - Misperceptions of speed are accounted for by the responses of neurons in macaque
      cortical area MT.
AB  - In humans, the perceived speed of random dot patterns (RDP) moving within small
      apertures is faster than that of RDPs moving within larger apertures at the same
      physical speed. To investigate the neural basis of this illusion, we recorded the
      responses of direction- and speed-selective neurons in the middle temporal area
      (MT) of macaque monkeys to stimuli varying in size and speed. Our results show
      that the preferred speed of MT neurons is slower for smaller stimuli. This effect
      was larger for neurons preferring faster speeds, matching our psychophysical
      observation in human subjects that the magnitude of the misperception is larger
      at higher stimulus speeds. Our physiological data indicate that, across a
      population of speed-tuned neurons in MT, decreasing the size of a stimulus would
      shift the activity profile to neurons tuned for higher speeds. Modeling a labeled
      line readout of this shifted profile, we show an increased apparent speed, in
      line with the psychophysical observations. This link strengthens the evidence for
      a causal role of area MT in speed perception. The systematic shift in tuning
      curves of single neurons with stimulus size might reflect a general mechanism for
      feature-mismatch illusions in visual perception.

PMID- 21191093
TI  - Pressure-volume relationships in patients with transthyretin (ATTR) cardiac
      amyloidosis secondary to V122I mutations and wild-type transthyretin:
      Transthyretin Cardiac Amyloid Study (TRACS).
AB  - BACKGROUND: ATTR cardiac amyloidosis can result from a mutated variant of
      transthyretin (eg, V122I) or wild-type variant (ATTRwt). We evaluated pressure
      volume (PV) indices at baseline and over time to further characterize abnormal
      pump function in these subjects. METHODS AND RESULTS: Twenty-nine subjects (18
      with ATTRwt and 11 with ATTRm (V122I) had 2-dimensional echocardiograms with
      complete Doppler measures at baseline and every 6 months for up to 2 years. PV
      indices were derived from echocardiographic measures of ventricular volume
      coupled with sphygmomanometer-measured pressure and Doppler estimates of filling
      pressure. The end-systolic and end-diastolic PV relations and the area between
      them as a function of end-diastolic pressure, the isovolumic PV area (PVA(iso)),
      were calculated. Clinical, demographic, and PV indices were compared between
      V122I and ATTRwt subjects and between survivors and nonsurvivors at baseline and
      over time. Cox proportional hazards model identified correlates for mortality.
      Stroke volume decline was associated with alterations in ventricular-vascular
      coupling and a decrease in ventricular capacitance with significant decrement in
      ejection fraction (56+/-12% to 48+/-14%, P=0.0001) over 18 months. PVA(iso) was
      lower in V122I subjects compared with wild-type at baseline and declined over
      time. Twelve (41%) subjects died or underwent a cardiac transplant after a mean
      follow-up of 478 days (range, 31 to 807). Multivariable survival analysis
      demonstrated that initial ejection fraction (a measure of ventricular-vascular
      coupling) <50% was associated with increased mortality (hazard ratio, 6.6; 95%
      confidence interval, 1.1 to 40.3). CONCLUSIONS: In ATTR cardiac amyloidosis
      secondary to a V122I mutation and wild-type transthyretin, PV analysis reveals
      alterations that are associated with reductions in the ability of the ventricle
      to perform work and, ultimately, with reduced survival in these subjects.

PMID- 21191094
TI  - A review of documented oral care practices in an intensive care unit.
AB  - Oral care is recognized as an essential component of care for critically ill
      patients and nursing documentation provides evidence of this process. This study
      examined the practice and frequency of oral care among mechanically ventilated
      and nonventilated patients. A retrospective record review was conducted of
      patients admitted to an intensive care unit (ICU) between July 1, 2007 and
      December 31, 2007. Data were analyzed using bivariate and multivariate analyses
      to determine the variables related to patients receiving oral care. Frequency of
      oral care documentation was found to be performed, on average, every 3.17 to 3.51
      hr with a range of 1 to 8 hr suggesting inconsistencies in nursing practice. This
      study found that although oral care is a Center for Disease Control and
      Prevention (CDC) recommendation for the prevention of hospital-associated
      infections like ventilator-associated pneumonia (VAP), indication of
      documentation of the specifics are lacking in the patients' medical record.

PMID- 21191095
TI  - Eating for pleasure or profit: the effect of incentives on children's enjoyment
      of vegetables.
AB  - Parents commonly use rewards to encourage children to eat healthfully, but this
      practice remains controversial because rewards are suspected of undermining
      children's intrinsic motivation. A cluster-randomized trial examined children's
      acceptance of a disliked vegetable over 12 daily taste exposures. These exposures
      were paired with a tangible reward, a social reward, or no reward, and the
      findings were compared with the results from a no-treatment control condition.
      Liking and intake of the vegetable were assessed in a free-choice consumption
      task at preintervention, postintervention, 1 month after intervention, and 3
      months after intervention. Liking increased more in the three intervention
      conditions than in the control condition, and there were no significant
      differences between the intervention conditions. These effects were maintained at
      follow-up. Children in both reward conditions increased consumption, and these
      effects were maintained for 3 months; however, the effects of exposure with no
      reward became nonsignificant by 3 months. These results indicate that external
      rewards do not necessarily produce negative effects and may be useful in
      promoting healthful eating.

PMID- 21191096
TI  - Proliferative and nonproliferative lesions of the rat and mouse hepatobiliary
      system.
AB  - The INHAND Project (International Harmonization of Nomenclature and Diagnostic
      Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of
      Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and
      North America (STP) to develop an internationally-accepted nomenclature for
      proliferative and non-proliferative lesions in laboratory animals. The purpose of
      this publication is to provide a standardized nomenclature and differential
      diagnosis for classifying microscopic lesions observed in the hepatobiliary
      system of laboratory rats and mice, with color microphotographs illustrating
      examples of some lesions. The standardized nomenclature presented in this
      document is also available for society members electronically on the internet
      (http://goreni.org). Sources of material included histopathology databases from
      government, academia, and industrial laboratories throughout the world. Content
      includes spontaneous and aging lesions as well as lesions induced by exposure to
      test materials. A widely accepted and utilized international harmonization of
      nomenclature for lesions of the hepatobiliary system in laboratory animals will
      decrease confusion among regulatory and scientific research organizations in
      different countries and provide a common language to increase and enrich
      international exchanges of information among toxicologists and pathologists.

PMID- 21191097
TI  - Spatial gradient of protein phosphorylation underlies replicative asymmetry in a
      bacterium.
AB  - Spatial asymmetry is crucial to development. One mechanism for generating
      asymmetry involves the localized synthesis of a key regulatory protein that
      diffuses away from its source, forming a spatial gradient. Although gradients are
      prevalent in eukaryotes, at both the tissue and intracellular levels, it is
      unclear whether gradients of freely diffusible proteins can form within bacterial
      cells given their small size and the speed of diffusion. Here, we show that the
      bacterium Caulobacter crescentus generates a gradient of the active,
      phosphorylated form of the master regulator CtrA, which directly regulates DNA
      replication. Using a combination of mathematical modeling, single-cell
      microscopy, and genetic manipulation, we demonstrate that this gradient is
      produced by the polarly localized phosphorylation and dephosphorylation of CtrA.
      Our data indicate that cells robustly establish the asymmetric fates of daughter
      cells before cell division causes physical compartmentalization. More generally,
      our results demonstrate that uniform protein abundance may belie gradients and
      other sophisticated spatial patterns of protein activity in bacterial cells.

PMID- 21191098
TI  - Conservation of proteobacterial magnetosome genes and structures in an
      uncultivated member of the deep-branching Nitrospira phylum.
AB  - Magnetotactic bacteria (MTB) are a phylogenetically diverse group which uses
      intracellular membrane-enclosed magnetite crystals called magnetosomes for
      navigation in their aquatic habitats. Although synthesis of these prokaryotic
      organelles is of broad interdisciplinary interest, its genetic analysis has been
      restricted to a few closely related members of the Proteobacteria, in which
      essential functions required for magnetosome formation are encoded within a large
      genomic magnetosome island. However, because of the lack of cultivated
      representatives from other phyla, it is unknown whether the evolutionary origin
      of magnetotaxis is monophyletic, and it has been questioned whether homologous
      mechanisms and structures are present in unrelated MTB. Here, we present the
      analysis of the uncultivated "Candidatus Magnetobacterium bavaricum" from the
      deep branching Nitrospira phylum by combining micromanipulation and whole genome
      amplification (WGA) with metagenomics. Target-specific sequences obtained by WGA
      of cells, which were magnetically collected and individually sorted from sediment
      samples, were used for PCR screening of metagenomic libraries. This led to the
      identification of a genomic cluster containing several putative magnetosome genes
      with homology to those in Proteobacteria. A variety of advanced electron
      microscopic imaging tools revealed a complex cell envelope and an intricate
      magnetosome architecture. The presence of magnetosome membranes as well as
      cytoskeletal magnetosome filaments suggests a similar mechanism of magnetosome
      formation in "Cand. M. bavaricum" as in Proteobacteria. Altogether, our findings
      suggest a monophyletic origin of magnetotaxis, and relevant genes were likely
      transferred horizontally between Proteobacteria and representatives of the
      Nitrospira phylum.

PMID- 21191099
TI  - Strain-resolved community genomic analysis of gut microbial colonization in a
      premature infant.
AB  - The intestinal microbiome is a critical determinant of human health. Alterations
      in its composition have been correlated with chronic disorders, such as obesity
      and inflammatory bowel disease in adults, and may be associated with neonatal
      necrotizing enterocolitis in premature infants. Increasing evidence suggests that
      strain-level genomic variation may underpin distinct ecological trajectories
      within mixed populations, yet there have been few strain-resolved analyses of
      genotype-phenotype connections in the context of the human ecosystem. Here, we
      document strain-level genomic divergence during the first 3 wk of life within the
      fecal microbiota of an infant born at 28-wk gestation. We observed three
      compositional phases during colonization, and reconstructed and intensively
      curated population genomic datasets from the third phase. The relative abundance
      of two Citrobacter strains sharing ~99% nucleotide identity changed significantly
      over time within a community dominated by a nearly clonal Serratia population and
      harboring a lower abundance Enterococcus population and multiple plasmids and
      bacteriophage. Modeling of Citrobacter strain abundance suggests differences in
      growth rates and host colonization patterns. We identified genotypic variation
      potentially responsible for divergent strain ecologies, including hotspots of
      sequence variation in regulatory genes and intergenic regions, and in genes
      involved in transport, flagellar biosynthesis, substrate metabolism, and host
      colonization, as well as differences in the complements of these genes. Our
      results demonstrate that a community genomic approach can elucidate gut microbial
      colonization at the resolution required to discern medically relevant strain and
      species population dynamics, and hence improve our ability to diagnose and treat
      microbial community-mediated disorders.

PMID- 21191100
TI  - Profile of Anthony R. Cashmore. Interview by Prashant Nair.

PMID- 21191101
TI  - Bacterial biofilm shows persistent resistance to liquid wetting and gas
      penetration.
AB  - Most of the world's bacteria exist in robust, sessile communities known as
      biofilms, ubiquitously adherent to environmental surfaces from ocean floors to
      human teeth and notoriously resistant to antimicrobial agents. We report the
      surprising observation that Bacillus subtilis biofilm colonies and pellicles are
      extremely nonwetting, greatly surpassing the repellency of Teflon toward water
      and lower surface tension liquids. The biofilm surface remains nonwetting against
      up to 80% ethanol as well as other organic solvents and commercial biocides
      across a large and clinically important concentration range. We show that this
      property limits the penetration of antimicrobial liquids into the biofilm,
      severely compromising their efficacy. To highlight the mechanisms of this
      phenomenon, we performed experiments with mutant biofilms lacking ECM components
      and with functionalized polymeric replicas of biofilm microstructure. We show
      that the nonwetting properties are a synergistic result of ECM composition,
      multiscale roughness, reentrant topography, and possibly yet other factors
      related to the dynamic nature of the biofilm surface. Finally, we report the
      impenetrability of the biofilm surface by gases, implying defense capability
      against vapor-phase antimicrobials as well. These remarkable properties of B.
      subtilis biofilm, which may have evolved as a protection mechanism against native
      environmental threats, provide a new direction in both antimicrobial research and
      bioinspired liquid-repellent surface paradigms.

PMID- 21191102
TI  - Reversing chemoresistance by small molecule inhibition of the translation
      initiation complex eIF4F.
AB  - Deregulation of cap-dependent translation is associated with cancer initiation
      and progression. The rate-limiting step of protein synthesis is the loading of
      ribosomes onto mRNA templates stimulated by the heterotrimeric complex,
      eukaryotic initiation factor (eIF)4F. This step represents an attractive target
      for anticancer drug discovery because it resides at the nexus of the TOR
      signaling pathway. We have undertaken an ultra-high-throughput screen to identify
      inhibitors that prevent assembly of the eIF4F complex. One of the identified
      compounds blocks interaction between two subunits of eIF4F. As a consequence, cap
      dependent translation is inhibited. This compound can reverse tumor
      chemoresistance in a genetically engineered lymphoma mouse model by sensitizing
      cells to the proapoptotic action of DNA damage. Molecular modeling experiments
      provide insight into the mechanism of action of this small molecule inhibitor.
      Our experiments validate targeting the eIF4F complex as a strategy for cancer
      therapy to modulate chemosensitivity.

PMID- 21191103
TI  - Critical effect of dependency groups on the function of networks.
AB  - Current network models assume one type of links to define the relations between
      the network entities. However, many real networks can only be correctly described
      using two different types of relations. Connectivity links that enable the nodes
      to function cooperatively as a network and dependency links that bind the failure
      of one network element to the failure of other network elements. Here we present
      an analytical framework for studying the robustness of networks that include both
      connectivity and dependency links. We show that a synergy exists between the
      failure of connectivity and dependency links that leads to an iterative process
      of cascading failures that has a devastating effect on the network stability. We
      present exact analytical results for the dramatic change in the network behavior
      when introducing dependency links. For a high density of dependency links, the
      network disintegrates in a form of a first-order phase transition, whereas for a
      low density of dependency links, the network disintegrates in a second-order
      transition. Moreover, opposed to networks containing only connectivity links
      where a broader degree distribution results in a more robust network, when both
      types of links are present a broad degree distribution leads to higher
      vulnerability.

PMID- 21191105
TI  - Prostaglandin F2&alpha; stimulates PI3K/ERK/mTOR signaling and skeletal myotube
      hypertrophy.
AB  - Cyclooxygenase (COX) enzymes mediate the synthesis of proinflammatory
      prostaglandin (PG) species from cellular arachidonic acid. COX/PGs have been
      implicated in skeletal muscle growth/regeneration; however, the mechanisms by
      which PGs influence skeletal muscle adaptation are poorly understood. The present
      study aimed to investigate PGF(2alpha) signaling and its role in skeletal myotube
      hypertrophy. PGF(2alpha) or the FP receptor agonist fluprostenol increased C2C12
      myotube diameter. This effect was abolished by the FP receptor antagonist AL8810
      and mammalian target of rapamycin (mTOR) inhibition. PGF(2alpha) stimulated time-
      and dose-dependent increases in the phosphorylation of extracellular receptor
      kinase (ERK)1/2 (Thr202/Tyr204), p70S6 kinase (p70S6K) (Thr389 and
      Thr421/Ser424), and eukaryotic initiation factor 4G (eIF4G) (Ser1108) without
      influencing Akt (Ser473). Pretreatment with the phosphoinositide 3-kinase (PI3K)
      inhibitor LY294002 and the ERK inhibitor PD98059 blocked F prostanoid receptor
      signaling responses, whereas rapamycin blocked heightened p70S6K/eIF4G
      phosphorylation without influencing ERK1/2 phosphorylation. These data suggest
      that activation of the F prostanoid receptor is coupled to C2C12 myotube growth
      and intracellular signaling via a PI3K/ERK/mTOR-dependent pathway.

PMID- 21191104
TI  - Activation of group VI phospholipase A2 isoforms in cardiac endothelial cells.
AB  - The endothelium comprises a cellular barrier between the circulation and tissues.
      We have previously shown that activation of protease-activated receptor 1 (PAR-1)
      and PAR-2 on the surface of human coronary artery endothelial cells by tryptase
      or thrombin increases group VIA phospholipase A(2) (iPLA(2)beta) activity and
      results in production of multiple phospholipid-derived inflammatory metabolites.
      We isolated cardiac endothelial cells from hearts of iPLA(2)beta-knockout
      (iPLA(2)beta-KO) and wild-type (WT) mice and measured arachidonic acid (AA),
      prostaglandin I(2) (PGI(2)), and platelet-activating factor (PAF) production in
      response to PAR stimulation. Thrombin (0.1 IU/ml) or tryptase (20 ng/ml)
      stimulation of WT endothelial cells rapidly increased AA and PGI(2) release and
      increased PAF production. Selective inhibition of iPLA(2)beta with (S)-bromoenol
      lactone (5 MUM, 10 min) completely inhibited thrombin- and tryptase-stimulated
      responses. Thrombin or tryptase stimulation of iPLA(2)beta-KO endothelial cells
      did not result in significant PAF production and inhibited AA and PGI(2) release.
      Stimulation of cardiac endothelial cells from group VIB (iPLA(2)gamma)-KO mice
      increased PAF production to levels similar to those of WT cells but significantly
      attenuated PGI(2) release. These results indicate that cardiac endothelial cell
      PAF production is dependent on iPLA(2)beta activation and that both iPLA(2)beta
      and iPLA(2)gamma may be involved in PGI(2) release.

PMID- 21191106
TI  - NHERF1 and NHERF2 are necessary for multiple but usually separate aspects of
      basal and acute regulation of NHE3 activity.
AB  - Na(+)/H(+) exchanger 3 (NHE3) is expressed in the brush border (BB) of intestinal
      epithelial cells and accounts for the majority of neutral NaCl absorption. It has
      been shown that the Na(+)/H(+) exchanger regulatory factor (NHERF) family members
      of multi-PDZ domain-containing scaffold proteins bind to the NHE3 COOH terminus
      and play necessary roles in NHE3 regulation in intestinal epithelial cells. Most
      studies of NHE3 regulation have been in cell models in which NHERF1 and/or NHERF2
      were overexpressed. We have now developed an intestinal Na(+) absorptive cell
      model in Caco-2/bbe cells by expressing hemagglutinin (HA)-tagged NHE3 with an
      adenoviral infection system. Roles of NHERF1 and NHERF2 in NHE3 regulation were
      determined, including inhibition by cAMP, cGMP, and Ca(2+) and stimulation by
      EGF, with knockdown (KD) approaches with lentivirus (Lenti)-short hairpin RNA
      (shRNA) and/or adenovirus (Adeno)-small interfering RNA (siRNA). Stable infection
      of Caco-2/bbe cells by NHERF1 or NHERF2 Lenti-shRNA significantly and
      specifically reduced NHERF protein expression by >80%. NHERF1 KD reduced basal
      NHE3 activity, while NHERF2 KD stimulated NHE3 activity. siRNA-mediated
      (transient) and Lenti-shRNA-mediated (stable) gene silencing of NHERF2 (but not
      of NHERF1) abolished cGMP- and Ca(2+)-dependent inhibition of NHE3. KD of NHERF1
      or NHERF2 alone had no effect on cAMP inhibition of NHE3, but KD of both
      simultaneously abolished the effect of cAMP. The stimulatory effect of EGF on
      NHE3 was eliminated in NHERF1-KD but occurred normally in NHERF2-KD cells. These
      findings show that both NHERF2 and NHERF1 are involved in setting NHE3 activity.
      NHERF2 is necessary for cGMP-dependent protein kinase (cGK) II- and Ca(2+)
      dependent inhibition of NHE3. cAMP-dependent inhibition of NHE3 activity requires
      either NHERF1 or NHERF2. Stimulation of NHE3 activity by EGF is NHERF1 dependent.

PMID- 21191107
TI  - Acquisition of dietary copper: a role for anion transporters in intestinal apical
      copper uptake.
AB  - Copper is an essential micronutrient in humans and is required for a wide range
      of physiological processes, including neurotransmitter biosynthesis, oxidative
      metabolism, protection against reactive oxygen species, and angiogenesis. The
      first step in the acquisition of dietary copper is absorption from the intestinal
      lumen. The major human high-affinity copper uptake protein, human copper
      transporter hCTR1, was recently shown to be at the basolateral or blood side of
      both intestinal and renal epithelial cell lines and thus does not play a direct
      role in this initial step. We sought to functionally identify the major transport
      pathways available for the absorption of dietary copper across the apical
      intestinal membrane using Caco2 cells, a well-established model for human
      enterocytes. The initial rate of apical copper uptake into confluent monolayers
      of Caco2 cells is greatly elevated if amino acids and serum proteins are removed
      from the growth media. Uptake from buffered saline solutions at neutral pH (but
      not at lower pH) is inhibited by either d- or l-histidine, unaltered by the
      removal of sodium ions, and inhibited by ~90% when chloride ions are replaced by
      gluconate or sulfate. Chloride-dependent copper uptake occurs with Cu(II) or
      Cu(I), although Cu(I) uptake is not inhibited by histidine, nor by silver ions. A
      well-characterized inhibitor of anion exchange systems, DIDS, inhibited apical
      copper uptake by 60-70%, while the addition of Mn(II) or Fe(II), competitive
      substrates for the divalent metal transporter DMT1, had no effect on copper
      uptake. We propose that anion exchangers play an unexpected role in copper
      absorption, utilizing copper-chloride complexes as pseudo-substrates. This
      pathway is also observed in mouse embryonic fibroblasts, human embryonic kidney
      cells, and Cos-7 cells. The special environment of low pH, low concentration of
      protein, and protonation of amino acids in the early intestinal lumen make this
      pathway especially important in dietary copper acquisition.

PMID- 21191108
TI  - Sphingomyelin synthase 2 (SMS2) deficiency attenuates LPS-induced lung injury.
AB  - Sphingomyelin synthase (SMS) catalyzes the synthesis of sphingomyelin (SM) and is
      required for maintenance of plasma membrane microdomain fluidity. Of the two
      isoforms of mammalian SMS, SMS1 is mostly present in the trans-Golgi apparatus,
      whereas SMS2 is predominantly found at the plasma membrane. SMS2 has a role in
      receptor mediated response to inflammation in macrophages, however, the role of
      SMS2 in vascular permeability, pulmonary edema, and lung injury have not been
      investigated. To define the role of SMS activation in lung injury, we utilized a
      lipopolysaccharide (LPS)-induced lung edema model. SMS activity was measured and
      correlated with the severity of lung injury. Within 4 h of LPS treatment, SMS
      activity was increased significantly and remained upregulated up to 24 h.
      Comparison of LPS-induced lung injury in SMS2 knockout (SMS2(-/-)) and wild-type
      littermate control mice showed that inflammation, cytokine induction, and lung
      injury were significantly inhibited in SMS2(-/-) mice. Our results suggest that a
      deficiency of SMS2 can diminish the extent of pulmonary edema and lung injury.
      Furthermore, we show that depletion of SMS2 was sufficient to decrease MAP kinase
      JNK activation, severity of LPS-induced pulmonary neutrophil influx, and
      inflammation, suggesting a novel role of SMS2 activation in lung injury.

PMID- 21191109
TI  - In vivo and in vitro aging is detrimental to mouse spermatogonial stem cell
      function.
AB  - The development of techniques to maintain the spermatogonial stem cell (SSC) in
      vivo and in vitro for extended periods essentially allows for the indefinite
      continuation of an individual germline. Recent evidence indicates that the aging
      of male reproductive function is due to failure of the SSC niche. SSCs are
      routinely cultured for 6 mo, and no apparent effect of culture over this period
      has been observed. To determine the effects of SSC aging, we utilized an in vitro
      culture system, followed by quantitative transplantation experiments. After
      culture for 6 mo, SSCs that had been aged in vivo for 1500 days had a slower
      proliferation rate than SSCs that were aged in vivo to 8 or 300 days. Examination
      of methylation patterns revealed no apparent difference in DNA methylation
      between SSCs that were aged 8, 300, or 1500 days before culture. Long-term
      culture periods resulted in a loss of stem cell potential without an obvious
      change in the visual appearance of the culture. DNA microarray analysis of in
      vivo- and in vitro-aged SSCs identified the differential expression of several
      genes important for SSC function, including B-cell CLL/lymphoma 6, member B
      (Bcl6b), Lim homeobox protein 1 (Lhx1), and thymus cell antigen 1, theta (Thy1).
      Collectively, these data indicate that, although both in vitro and in vivo aging
      are detrimental to SSC function, in vitro aging results in greater loss of
      function, potentially due to a decrease in core SSC self-renewal gene expression
      and an increase in germ cell differentiation gene expression.

PMID- 21191110
TI  - Protein kinase C delta mediates fibroblast growth factor-2-induced interferon-tau
      expression in bovine trophoblast.
AB  - Interferon-tau (IFNT) is the trophoblast-secreted factor responsible for
      establishing and maintaining pregnancy in ruminants. Several uterine- and embryo
      derived factors, including fibroblast growth factor-2 (FGF2), regulate IFNT
      production. The objective of the present study was to decipher the intracellular
      signaling mechanisms employed by FGF2 to regulate IFNT production. In bovine
      trophoblast cells (CT1), mitogen-activated protein kinase kinase-dependent
      pathways mediated constitutive IFNT mRNA concentrations. However, FGF2-mediated
      increases in IFNT mRNA levels occurs independent of mitogen-activated protein
      kinase. Exposure to the pan-protein kinase C (PKC) inhibitor, calphostin C, did
      not affect basal IFNT mRNA levels but limited the ability of FGF2 to increase
      IFNT mRNA abundance. Also, supplementation with phorbol 12-myristate 13-acetate
      (PMA) stimulated IFNT mRNA levels to the same extent as with FGF2. PMA and FGF2
      cosupplementation did not elicit an additive effect on IFNT mRNA abundance.
      Pharmacological antagonists for classic PKCs (Go6976) or novel PKCs, including
      PKC delta (rottlerin), were used to identify the specific PKC isoform utilized by
      FGF2. Supplementation of CT1 cells with Go6976 did not affect FGF2 or PMA
      activities, whereas rottlerin prevented FGF2- and PMA-dependent increases in IFNT
      mRNA abundance in CT1 cells. Rottlerin also prevented FGF2 from increasing IFNT
      mRNA levels in Vivot trophoblast cells and primary trophoblast outgrowths.
      Modifications in PRKCD phosphorylation status were evident following FGF2 and PMA
      treatment. Also, reducing PRKCD expression by RNA interference attenuated FGF2
      dependent increases in IFNT mRNA abundance. In conclusion, these results provide
      evidence that FGF2 regulates IFNT production in bovine trophectoderm by acting
      through PRKCD.

PMID- 21191112
TI  - Lung cancer screening: ready for prime time?

PMID- 21191111
TI  - PACAP, an autocrine/paracrine regulator of gonadotrophs.
AB  - Hypothalamic-hypophysiotropic peptides are the proximate regulators of pituitary
      cells, but they cannot fully account for the complex functioning of these cells.
      Accordingly, awareness is growing that an array of peptides produced in the
      pituitary exert paracrine/autocrine functions. One such peptide, pituitary
      adenylate cyclase-activating polypeptide (PACAP), was originally identified as a
      hypothalamic activator of cAMP production in pituitary cells. Gonadotrophs and
      folliculostellate cells are the main source of pituitary PACAP, and each
      pituitary cell type expresses a PACAP receptor. PACAP increases alpha-subunit
      (Cga) and Lhb mRNAs, and it stimulates the transcription of follistatin (Fst)
      that, in turn, restrains activin signaling to repress Fshb and gonadotropin
      releasing hormone-receptor (Gnrhr) expression as well as other activin-responsive
      genes. The PACAP (Adcyap1) promoter is activated by cAMP, and pituitary cells may
      communicate by a feed-forward, cAMP-dependent mechanism to maintain a high level
      of PACAP in the fetal pituitary. At birth, pituitary PACAP declines and pituitary
      follistatin levels decrease, which together with increased gonadotropin-releasing
      hormone secretion allow Gnrhr and Fshb to increase and facilitate activation of
      the newborn gonads. Changes in Adcyap1 expression levels in the adult pituitary
      may contribute to the selective rise in follicle-stimulating hormone (FSH) from
      age 20-30 days to the midcycle surge and to the secondary increase in FSH that
      occurs before estrus. These results provide further support for the notion that
      PACAP is a key player in reproduction through its actions as a pituitary
      autocrine/paracrine hormone.

PMID- 21191113
TI  - Ready or not: personal tumor profiling tests take off.

PMID- 21191114
TI  - How do you tell whether a breast cancer is HER2 positive? Ongoing studies keep
      debate in high gear.

PMID- 21191115
TI  - StatBite: Comparing radiation doses from screening procedures.

PMID- 21191116
TI  - Gene pathways associated with prognosis and chemotherapy sensitivity in molecular
      subtypes of breast cancer.
AB  - BACKGROUND: We hypothesized that distinct biological processes might be
      associated with prognosis and chemotherapy sensitivity in the different types of
      breast cancers. METHODS: We performed gene set analyses with BRB-ArrayTools
      statistical software including 2331 functionally annotated gene sets (ie, lists
      of genes that correspond to a particular biological pathway or biochemical
      function) assembled from Ingenuity Pathway Analysis and Gene Ontology databases
      corresponding to almost all known biological processes. Gene set analysis was
      performed on gene expression data from three cohorts of 234, 170, and 175
      patients with HER2-normal lymph node-negative breast cancer who received no
      systemic adjuvant therapy to identify gene sets associated prognosis and three
      additional cohorts of 198, 85, and 62 patients with HER2-normal stage I-III
      breast cancer who received preoperative chemotherapy to identify gene sets
      associated with pathological complete response to therapy. These analyses were
      performed separately for estrogen receptor (ER)-positive and ER-negative breast
      cancers. Interaction between gene sets and survival and treatment response by
      breast cancer subtype was assessed in individual datasets and also in pooled
      datasets. Statistical significance was estimated with permutation test. All
      statistical tests were two-sided. RESULTS: For ER-positive cancers, from 370 to
      434 gene sets were associated with prognosis (P <= .05) and from 209 to 267 gene
      sets were associated with chemotherapy response in analysis by individual
      dataset. For ER-positive cancers, 131 gene sets were associated with prognosis
      and 69 were associated with pathological complete response (P <=.001) in pooled
      analysis. Increased expression of cell cycle-related gene sets was associated
      with poor prognosis, and B-cell immunity-related gene sets were associated with
      good prognosis. For ER-negative cancers, from 175 to 288 gene sets were
      associated with prognosis and from 212 to 285 gene sets were associated with
      chemotherapy response. In pooled analyses of ER-negative cancers, 14 gene sets
      were associated with prognosis and 23 were associated with response. Gene sets
      involved in sphingolipid and glycolipid metabolism were associated with better
      prognosis and those involved in base excision repair, cell aging, and spindle
      microtubule regulation were associated with chemotherapy response. CONCLUSION:
      Different biological processes were associated with prognosis and chemotherapy
      response in ER-positive and ER-negative breast cancers.

PMID- 21191118
TI  - Decision making for HIV prevention and treatment scale up: bridging the gap
      between theory and practice.
AB  - BACKGROUND: Effectively controlling the HIV epidemic will require efficient use
      of limited resources. Despite ambitious global goals for HIV prevention and
      treatment scale up, few comprehensive practical tools exist to inform such
      decisions. METHODS: We briefly summarize modeling approaches for resource
      allocation for epidemic control, and discuss the practical limitations of these
      models. We describe typical challenges of HIV resource allocation in practice and
      some of the tools used by decision makers. We identify the characteristics needed
      in a model that can effectively support planners in decision making about HIV
      prevention and treatment scale up. RESULTS: An effective model to support HIV
      scale-up decisions will be flexible, with capability for parameter customization
      and incorporation of uncertainty. Such a model needs certain key technical
      features: it must capture epidemic effects; account for how intervention
      effectiveness depends on the target population and the level of scale up; capture
      benefit and cost differentials for packages of interventions versus single
      interventions, including both treatment and prevention interventions; incorporate
      key constraints on potential funding allocations; identify optimal or near
      optimal solutions; and estimate the impact of HIV interventions on the health
      care system and the resulting resource needs. Additionally, an effective model
      needs a user-friendly design and structure, ease of calibration and validation,
      and accessibility to decision makers in all settings. CONCLUSIONS: Resource
      allocation theory can make a significant contribution to decision making about
      HIV prevention and treatment scale up. What remains now is to develop models that
      can bridge the gap between theory and practice.

PMID- 21191119
TI  - Influence of graphic format on comprehension of risk information among American
      Indians.
AB  - BACKGROUND: Presentation of risk information influences patients' ability to
      interpret health care options. Little is known about this relationship between
      risk presentation and interpretation among American Indians. METHODS: Three
      hundred American Indian employees on a western American Indian reservation were
      invited to complete an anonymous written survey. All surveys included a vignette
      presenting baseline risk information about a hypothetical cancer and possible
      benefits of 2 prevention plans. Risk interpretation was assessed by correct
      answers to 3 questions evaluating the risk reduction associated with the plans.
      Numeric information was the same in all surveys, but framing varied; half
      expressed prevention benefits in terms of relative risk reduction and half in
      terms of absolute risk reduction. All surveys used text to describe the benefits
      of the 2 plans, but half included a graphic image. Surveys were distributed
      randomly. Responses were analyzed using binary logistic regression with the
      robust variance estimator to account for clustering of outcomes within
      participant. RESULTS: Use of a graphic image was associated with higher odds of
      correctly answering 3 risk interpretation questions (odds ratio = 2.5, 95%
      confidence interval = 1.5-4.0, P < 0.001) compared to the text-only format. These
      findings were similar to those of previous studies carried out in the general
      population. Neither framing information as relative compared to absolute risk nor
      the interaction between graphic image and relative risk presentation was
      associated with risk interpretation. CONCLUSION: One type of graphic image was
      associated with increased understanding of risk in a small sample of American
      Indian adults. The authors recommend further investigation of the effectiveness
      of other types of graphic displays for conveying health risk information to this
      population.

PMID- 21191120
TI  - Overestimation error and unnecessary antibiotic prescriptions for acute cystitis
      in adult women.
AB  - BACKGROUND: Empiric antibiotic prescribing for suspected acute cystitis may lead
      to unnecessary prescriptions when urine cultures are negative. This study
      assessed whether physician overestimation of the likelihood of bacterial
      infection contributed to unnecessary antibiotic prescriptions. METHODS: This was
      a cross-sectional study in Toronto, Canada, from 1998 to 2000 of 231 women 16
      years and older who underwent standardized clinical assessments and urine culture
      testing. The main outcome was an unnecessary antibiotic prescription, defined as
      a prescription where the urine culture was negative. The difference between
      physician estimates of the likelihood of a positive urine culture and the
      measured culture rate for women with similar symptoms was used to measure
      overestimation error. Logistic regression was used to assess associations between
      unnecessary prescriptions and clinical factors or overestimation error. Multiple
      logistic regression was used to adjust for the effect of clinical factors.
      RESULTS: Of 230 women assessed, 186 (80.9%) were prescribed antibiotics and 74
      (32.2%) were prescribed an unnecessary antibiotic where the urine culture was
      negative. When an overestimation error above the median value (14.75%) was
      present, the odds of an unnecessary antibiotic prescription were increased
      (adjusted odds ratio = 3.72; 95% confidence interval = 1.75-7.89). A high
      overestimation error was associated with the symptoms of urinary frequency or
      suprapubic tenderness and costovertebral angle tenderness on examination.
      CONCLUSIONS: Physician overestimation of the likelihood of a positive urine
      culture in women with symptoms of acute cystitis was associated with unnecessary
      antibiotic prescribing. Antibiotic overuse may be reduced by developing treatment
      strategies that deemphasize nonspecific clinical findings that contribute to
      physician overestimation error.

PMID- 21191121
TI  - Trends in medical end-of-life decision making in Flanders, Belgium 1998-2001
      2007.
AB  - In 2002, Belgium saw the enactment of 3 laws concerning euthanasia, palliative
      care, and patient rights that are likely to affect end-of-life decision making.
      This report examines trends in the occurrence and decision-making process of end
      of-life practices in different patient groups since these legal changes. A large
      scale retrospective survey in Flanders, Belgium, previously conducted in 1998 and
      2001, was repeated in 2007. Questionnaires regarding end-of-life practices and
      the preceding decision-making process were mailed to physicians who certified a
      representative sample (N = 6927) of death certificates. The 2007 response rate
      was 58.4%. In patient groups in which the prevalence of life-ending drug use
      without explicit patient request has dropped, performance of euthanasia and
      assisted suicide has increased. The consistent increase in intensified pain and
      symptom alleviation was found in all patient groups except cancer patients. In
      2007, competent patients were slightly more often involved in the discussion of
      end-of-life practices than in previous years. Over the years, involvement of the
      patient in decision making was consistently more likely among younger patients,
      cancer patients, and those dying at home. Physicians consulted their colleagues
      more often than in previous years for euthanasia and nontreatment decisions. The
      euthanasia law and emerging palliative care culture have substantially affected
      the occurrence and decision making for end-of-life practices in Belgium. Efforts
      are still needed to encourage shared end-of-life decision making, as some
      patients would benefit from advance care planning.

PMID- 21191122
TI  - Informing patients: the influence of numeracy, framing, and format of side effect
      information on risk perceptions.
AB  - BACKGROUND: Given the importance of effective patient communication, findings
      about influences on risk perception in nonmedical domains need replication in
      medical domains. OBJECTIVE: To examine whether numeracy influences risk
      perceptions when different information frames and number formats are used to
      present medication risks. METHODS: The authors manipulated the frame and number
      format of risk information in a 3 (frame: positive, negative, combined) * 2
      (number format: frequency, percentage) design. Participants from an Internet
      sample (N = 298), randomly assigned to condition, responded to a single,
      hypothetical scenario. The main effects and interactions of numeracy, framing,
      and number format on risk perception were measured. RESULTS: Participants given
      the positive frame perceived the medication as less risky than those given the
      negative frame. Mean risk perceptions for the combined frame fell between the
      positive and negative frames. Numeracy did not moderate these framing effects.
      Risk perceptions also varied by number format and numeracy, with less-numerate
      participants given risk information in a percentage format perceiving the
      medication as less risky than when given risk information in a frequency format;
      highly numerate participants perceived similar risks in both formats. The
      generalizability of the findings is limited due to the use of non-patients,
      presented a hypothetical scenario. Given the design, one cannot know whether
      observed differences would translate into clinically significant differences in
      patient behaviors. CONCLUSIONS: Frequency formats appear to increase risk
      perceptions over percentage formats for less-numerate respondents. Health
      communicators need to be aware that different formats generate different risk
      perceptions among patients varying in numeracy.

PMID- 21191117
TI  - Associations of breast cancer risk factors with tumor subtypes: a pooled analysis
      from the Breast Cancer Association Consortium studies.
AB  - BACKGROUND: Previous studies have suggested that breast cancer risk factors are
      associated with estrogen receptor (ER) and progesterone receptor (PR) expression
      status of the tumors. METHODS: We pooled tumor marker and epidemiological risk
      factor data from 35,568 invasive breast cancer case patients from 34 studies
      participating in the Breast Cancer Association Consortium. Logistic regression
      models were used in case-case analyses to estimate associations between
      epidemiological risk factors and tumor subtypes, and case-control analyses to
      estimate associations between epidemiological risk factors and the risk of
      developing specific tumor subtypes in 12 population-based studies. All
      statistical tests were two-sided. RESULTS: In case-case analyses, of the
      epidemiological risk factors examined, early age at menarche (<=12 years) was
      less frequent in case patients with PR(-) than PR(+) tumors (P = .001).
      Nulliparity (P = 3 * 10(-6)) and increasing age at first birth (P = 2 * 10(-9))
      were less frequent in ER(-) than in ER(+) tumors. Obesity (body mass index [BMI]
      >= 30 kg/m(2)) in younger women (<=50 years) was more frequent in ER(-)/PR(-)
      than in ER(+)/PR(+) tumors (P = 1 * 10(-7)), whereas obesity in older women (>50
      years) was less frequent in PR(-) than in PR(+) tumors (P = 6 * 10(-4)). The
      triple-negative (ER(-)/PR(-)/HER2(-)) or core basal phenotype (CBP; triple
      negative and cytokeratins [CK]5/6(+) and/or epidermal growth factor receptor
      [EGFR](+)) accounted for much of the heterogeneity in parity-related variables
      and BMI in younger women. Case-control analyses showed that nulliparity,
      increasing age at first birth, and obesity in younger women showed the expected
      associations with the risk of ER(+) or PR(+) tumors but not triple-negative
      (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] =
      0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR =
      0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95% CI
      = 0.95 to 1.94, P = .09) or CBP tumors. CONCLUSIONS: This study shows that
      reproductive factors and BMI are most clearly associated with hormone receptor
      positive tumors and suggest that triple-negative or CBP tumors may have distinct
      etiology.

PMID- 21191124
TI  - Total NIH support to US dental schools, 2005-2009.
AB  - This study compared total NIH research funding across US dental institutions from
      2005 to 2009. Utilizing the online NIH RePORT, we obtained comprehensive award
      data for US dental schools by funding NIH Institutes/Centers (ICs). Fifty dental
      schools were awarded a total of $974.393 million, 69.3% from NIDCR and 30.7% from
      21 other ICs. These provided the majority of support to 12 schools. Greater than
      50% of non-NIDCR support came from 4 ICs. The median dental school NIH portfolio
      was $14.572 million, with a minimum of $0.241 million and a maximum of $88.609
      million. Forty-six schools received $544.899 million for R01 awards. Thirty-five
      schools were awarded $100 million in research training and career development
      grants. Several dramatic differences are found for dental schools' rankings based
      on total NIH dollars compared with NIDCR-only support. Dollars from ICs other
      than NIDCR increased 34.6% between 2005 and 2009. Grants to US dental
      institutions comprised 50% or less of total NIDCR awards globally from 2005
      through 2009. Funds received from all NIH ICs are an objective metric for
      evaluation of the research performance of dental schools. NIDCR has played a
      diminishing role in funding research at US dental schools between 2005 and 2009.

PMID- 21191123
TI  - Deceiving numbers: survival rates and their impact on doctors' risk
      communication.
AB  - BACKGROUND: Increased 5-y survival for screened patients is often inferred to
      mean that fewer patients die of cancer. However, due to several biases, the 5-y
      survival rate is a misleading metric for evaluating a screening's effectiveness.
      If physicians are not aware of these issues, informed screening counseling cannot
      take place. METHODS: Two questionnaire versions ("group" and "time") presented 4
      conditions: 5-y survival (5Y), 5-y survival and annual disease-specific mortality
      (5YM), annual disease-specific mortality (M), and 5-y survival, annual disease
      specific mortality, and incidence (5YMI). Questionnaire version "time" presented
      data as a comparison between 2 time points and version "group" as a comparison
      between a screened and an unscreened group. All data were based on statistics for
      the same cancer site (prostate). Outcome variables were the recommendation of
      screening, reasoning behind recommendation, judgment of the screening's
      effectiveness, and, if judged effective, a numerical estimate of how many fewer
      people out of 1000 would die if screened regularly. After randomized allocation,
      65 German physicians in internal medicine and its subspecialities completed
      either of the 2 questionnaire versions. RESULTS: Across both versions, 66% of the
      physicians recommended screening when presented with 5Y, but only 8% of the same
      physicians made the recommendation when presented with M (5YM: 31%; 5YMI: 55%).
      Also, 5Y made considerably more physicians (78%) judge the screening to be
      effective than any other condition (5YM: 31%; M: 5%; 5YMI: 49%) and led to the
      highest overestimations of benefit. CONCLUSION: A large number of physicians
      erroneously based their screening recommendation and judgment of screening's
      effectiveness on the 5-y survival rate. Results show that reporting disease
      specificmortality rates can offer a simple solution to physicians' confusion
      about the real effect of screening.

PMID- 21191125
TI  - New evidence of dental pathology in 40,000-year-old Neandertals.

PMID- 21191126
TI  - LPS induces greater bone and PDL loss in SPARC-null mice.
AB  - Individuals with periodontal disease have increased risk of tooth loss,
      particularly in cases with associated loss of alveolar bone and periodontal
      ligament (PDL). Current treatments do not predictably regenerate damaged PDL.
      Collagen I is the primary component of bone and PDL extracellular matrix.
      SPARC/Osteonectin (SP/ON) is implicated in the regulation of collagen content in
      healthy PDL. In this study, periodontal disease was induced by injections of
      lipopolysaccharide (LPS) from Aggregatibacter actinomycetemcomitans in wild-type
      (WT) and SP/ON-null C57/Bl6 mice. A 20-ug quantity of LPS was injected between
      the first and second molars 3 times a week for 4 weeks, whereas PBS control was
      injected into the contralateral maxilla. LPS injection resulted in a significant
      decrease in bone volume fraction in both genotypes; however, significantly
      greater bone loss was detected in SP/ON-null maxilla. SP/ON-null PDL exhibited
      more extensive degradation of connective tissue in the gingival tissues. Although
      total cell numbers in the PDL of SP/ON-null were not different from those in WT,
      the inflammatory infiltrate was reduced in SP/ON-null PDL. Histology of collagen
      fibers revealed marked reductions in collagen volume fraction and in thick
      collagen volume fraction in the PDL of SP/ON-null mice. SP/ON protects collagen
      content in PDL and in alveolar bone in experimental periodontal disease.

PMID- 21191127
TI  - Dentin hypersensitivity and oxalates: a systematic review.
AB  - Treatment of dentin hypersensitivity with oxalates is common, but oxalate
      efficacy remains unclear. Our objective was to systematically review clinical
      trials reporting an oxalate treatment compared with no treatment or placebo with
      a dentin hypersensitivity outcome. Risk-of-bias assessment and data extraction
      were performed independently by two reviewers. Standardized mean differences
      (SMD) were estimated by random-effects meta-analysis. Of 677 unique citations, 12
      studies with high risk-of-bias were included. The summary SMD for 3% monohydrogen
      monopotassium oxalate (n = 8 studies) was -0.71 [95% Confidence Interval: -1.48,
      0.06]. Other treatments, including 30% dipotassium oxalate (n = 1), 30%
      dipotassium oxalate plus 3% monohydrogen monopotassium oxalate (n = 3), 6%
      monohydrogen monopotassium oxalate (n = 1), 6.8% ferric oxalate (n = 1), and
      oxalate-containing resin (n = 1), also were not statistically significantly
      different from placebo treatments. With the possible exception of 3% monohydrogen
      monopotassium oxalate, available evidence currently does not support the
      recommendation of dentin hypersensitivity treatment with oxalates.

PMID- 21191129
TI  - Reducing backward masking through action game training.
AB  - Action video game play enhances basic visual skills such as crowding acuity and
      contrast sensitivity (C. S. Green & D. Bavelier, 2007; R. Li, U. Polat, W.
      Makous, & D. Bavelier, 2009). Here, we ask whether the dynamics of perception may
      also be altered as a result of playing action games. A backward masking paradigm
      was used to test the hypothesis that action video game play also alters the
      temporal dynamics of vision. As predicted, action gamers showed reduced backward
      masking and an accompanying training study established the causal role of action
      game play in this enhancement. Implications of this result are discussed in the
      context of the faster reaction times and enhanced sensitivity also documented
      after action game play.

PMID- 21191131
TI  - Evidence from vergence eye movements that disparities defined by luminance and
      contrast are sensed by independent mechanisms.
AB  - We recorded the initial disparity vergence responses (DVRs) elicited by 1-D
      sinusoidal gratings differing in phase at the two eyes by 1/4 wavelength and
      defined by luminance modulation (LM) or contrast modulation (CM) of dynamic
      binary noise. Both LM and CM stimuli elicited DVRs, but those to CM had longer
      latency (on average by ~20 ms). DVRs showed sigmoidal dependence on depth of
      modulation, with higher thresholds for CM than for LM. With both LM and CM
      stimuli, fixing the modulation at one eye well above threshold rendered the DVR
      hypersensitive to low-level modulation at the other eye (dichoptic facilitation).
      Disparities defined by LM at one eye and CM at the other generated weak DVRs in
      the "wrong" direction, consistent with mediation entirely by distortion products
      associated with the CM stimulus. These (reversed) DVRs could be nulled by adding
      LM to the CM stimulus (in phase), and the greater the depth of the CM, the
      greater the added LM required for nulling, exactly as predicted by a simple
      compressive non-linearity. We conclude that disparities defined by LM and by CM
      are sensed by independent cortical mechanisms, at least for the purposes of
      generating short-latency vergence eye movements to disparity steps.

PMID- 21191130
TI  - Simulating prosthetic vision: Optimizing the information content of a limited
      visual display.
AB  - Visual prostheses for the restoration of functional vision are currently under
      development. To guide prosthesis research and allow for an accurate prognosis of
      functional gain, simulating the experience of a retinal prosthesis in healthy
      individuals is desirable. Current simulation paradigms lack crucial aspects of
      the prosthetic experience such as realistic head- and eye-position-dependent
      image presentation. We developed a simulation paradigm that used a head-mounted
      camera and eye tracker to lock the simulation to the point of fixation. We
      evaluated visual acuity, object recognition and manipulation, and wayfinding
      under simulated prosthetic vision. We explored three ways of optimizing the
      information content of the prosthetic visual image: Full-Field representation
      (wide visual angle, low sampling frequency), Region of Interest (ROI; narrow
      visible angle, high sampling frequency), and Fisheye (high sampling frequency in
      the center, progressively lower resolution toward the edges). Full-Field
      representation facilitated visual search and navigation, whereas ROI improved
      visual acuity. The Fisheye representation, designed to incorporate the benefits
      of both Full-Field representation and ROI, performed similarly to ROI with
      subjects unable to capitalize on the peripheral data. The observation that
      different image representation conditions prove advantageous for different tasks
      should be taken into account in the process of designing and testing new visual
      prosthesis prototypes.

PMID- 21191132
TI  - Experience affects the use of ego-motion signals during 3D shape perception.
AB  - Experience has long-term effects on perceptual appearance (Q. Haijiang, J. A.
      Saunders, R. W. Stone, & B. T. Backus, 2006). We asked whether experience affects
      the appearance of structure-from-motion stimuli when the optic flow is caused by
      observer ego-motion. Optic flow is an ambiguous depth cue: a rotating object and
      its oppositely rotating, depth-inverted dual generate similar flow. However, the
      visual system exploits ego-motion signals to prefer the percept of an object that
      is stationary over one that rotates (M. Wexler, F. Panerai, I. Lamouret, & J.
      Droulez, 2001). We replicated this finding and asked whether this preference for
      stationarity, the "stationarity prior," is modulated by experience. During
      training, two groups of observers were exposed to objects with identical flow,
      but that were either stationary or moving as determined by other cues. The
      training caused identical test stimuli to be seen preferentially as stationary or
      moving by the two groups, respectively. We then asked whether different priors
      can exist independently at different locations in the visual field. Observers
      were trained to see objects either as stationary or as moving at two different
      locations. Observers' stationarity bias at the two respective locations was
      modulated in the directions consistent with training. Thus, the utilization of
      extraretinal ego-motion signals for disambiguating optic flow signals can be
      updated as the result of experience, consistent with the updating of a Bayesian
      prior for stationarity.

PMID- 21191133
TI  - The role of "rescue saccades" in tracking objects through occlusions.
AB  - We hypothesize that our ability to track objects through occlusions is mediated
      by timely assistance from gaze in the form of "rescue saccades"-eye movements to
      tracked objects that are in danger of being lost due to impending occlusion.
      Observers tracked 2-4 target sharks (out of 9) for 20 s as they swam through a
      rendered 3D underwater scene. Targets were either allowed to enter into
      occlusions (occlusion trials) or not (no occlusion trials). Tracking accuracy
      with 2-3 targets was >= 92% regardless of target occlusion but dropped to 74% on
      occlusion trials with four targets (no occlusion trials remained accurate; 83%).
      This pattern was mirrored in the frequency of rescue saccades. Rescue saccades
      accompanied approximatlely 50% of the Track 2-3 target occlusions, but only 34%
      of the Track 4 occlusions. Their frequency also decreased with increasing
      distance between a target and the nearest other object, suggesting that it is the
      potential for target confusion that summons a rescue saccade, not occlusion
      itself. These findings provide evidence for a tracking system that monitors for
      events that might cause track loss (e.g., occlusions) and requests help from the
      oculomotor system to resolve these momentary crises. As the number of crises
      increase with the number of targets, some requests for help go unsatisfied,
      resulting in degraded tracking.

PMID- 21191135
TI  - Automaticity of online control processes in manual aiming.
AB  - Experiments that manipulated the visual feedback of the moving limb have
      suggested the existence of efficient and automatic online correction processes.
      We wanted to determine whether the latency/gain of the correction for a cursor
      jump are only influenced by the size of the cursor jump or whether they are also
      influenced by the need of a correction for the target to be reached. In
      Experiment 1, we used two target sizes (5 and 30 mm) and three cursor-jump
      amplitudes (5, 15, and 25 mm), so that for some target size/cursor-jump
      combinations, no correction would be needed to reach the target. Participants
      were not aware of the cursor jump, but we observed a 65% correction regardless of
      target size. In Experiment 2, participants pointed at a large target for which a
      15-mm cursor jump never impeded target attainment. Participants modified the
      trajectory of their movement in the direction opposite to the cursor jump (42% of
      the cursor jump). Our results indicate that the latency of the correction for a
      cursor jump was not influenced by the size of the cursor jump or that of the
      target. However, the correction tailored the movement's initial impulse according
      to the target's characteristics.

PMID- 21191134
TI  - Eye movement sequence generation in humans: Motor or goal updating?
AB  - Saccadic eye movements are often grouped in pre-programmed sequences. The
      mechanism underlying the generation of each saccade in a sequence is currently
      poorly understood. Broadly speaking, two alternative schemes are possible: first,
      after each saccade the retinotopic location of the next target could be
      estimated, and an appropriate saccade could be generated. We call this the goal
      updating hypothesis. Alternatively, multiple motor plans could be pre-computed,
      and they could then be updated after each movement. We call this the motor
      updating hypothesis. We used McLaughlin's intra-saccadic step paradigm to
      artificially create a condition under which these two hypotheses make
      discriminable predictions. We found that in human subjects, when sequences of two
      saccades are planned, the motor updating hypothesis predicts the landing position
      of the second saccade in two-saccade sequences much better than the goal updating
      hypothesis. This finding suggests that the human saccadic system is capable of
      executing sequences of saccades to multiple targets by planning multiple motor
      commands, which are then updated by serial subtraction of ongoing motor output.

PMID- 21191136
TI  - A cyclopean visual saltation illusion reveals perceptual grouping in three
      dimensional space.
AB  - When a number of visual elements are presented briefly one after the other at two
      separate locations, mislocalization occurs with elements perceived "jumping"
      evenly across the space between locations. This is the visual saltation illusion.
      We investigated whether saltation occurs in three-dimensional (3D) space. In
      separate experiments, observers judged the perceived positions of the first,
      second, and last elements for a sequence in which the first two elements were
      presented at one location, and the third was presented at a second location. If
      saltation occurred, only the second element was mislocalized to a position
      between the first and second locations. In Experiment 1, we observed 3D
      saltation, but only for conditions in which the stimulus was located away from
      the point of fixation. This effect was also observed when the two locations in
      depth have no lateral 2D separation (Experiment 2). In Experiment 3, we showed
      that a locally generated motion aftereffect between the two locations distorts
      the perceived position in depth of only the second element, which perceptually
      overlaps with the adapted region. Our results demonstrate the appearance of 3D
      saltation, and that the illusion represents a process in which higher cortical
      areas feed back to activate lower level inputs to achieve 3D perceptual "filling
      in."

PMID- 21191137
TI  - When and where is binocular rivalry resolved in the visual cortex?
AB  - Anatomically "early" visual areas including striate cortex (V1) are known to play
      a role in the resolution of binocular rivalry. However, the time course of such
      activity and its relationship with subjective perception are unclear. The present
      study used an intermittent stimulation design to measure event-related potentials
      (ERPs) associated with perception during binocular rivalry and during physical
      alternations of the same stimuli. When gratings of high or low spatial
      frequencies were presented in physical alternation, the amplitude of the earliest
      cortical ERP component (the C1, at 60-100 ms) was larger for high spatial
      frequencies. When the same two stimuli competed during rivalry, however, C1
      amplitudes were equivalent for perceptions of high versus low spatial frequency.
      These findings suggest that rivalry is not resolved before or during the initial
      cortical response at 60-100 ms. At longer latencies (approximately 130-160 ms),
      however, occipital ERPs with similar topographies and estimated sources as the C1
      differed according to perception in both the rivalry and physical alternation
      conditions. These results suggest that during rivalry, neural activity coupled
      with the dominant percept first emerges in anatomically early visual cortex, but
      at delayed latencies.

PMID- 21191138
TI  - Cardioprotective effect of Nerium oleander flower against isoproterenol-induced
      myocardial oxidative stress in experimental rats.
AB  - Nerium oleander Linn (NOL) an evergreen shrub belonging to the Apocynaceae family
      has been reported to have a wide spectrum of bioactivities. In in vitro study,
      the free radical scavenging potential of the hydroethanolic extract of N oleander
      Linn (ENO) flower and its fractions (glycosidic and nonglycosidic) were studied
      using 2, 2(')-azino-di [3-ethylbenzthiazoline sulphonate] (ABTS(*+) ) and 1, 1
      diphenyl-2-picrylhydrazyl (DPPH*) scavenging assay. ENO exhibited better radical
      scavenging activities than its fractions. Furthermore, the cardioprotective role
      of ENO (10, 30, 100 mg/kg, per oral [po]) was tested against isoproterenol
      induced myocardial toxicity (ISO, 120 mg/kg per day, subcutaneously [sc], for 2
      days at 48 hours interval) in experimental rats when compared to propranolol (5
      mg/kg, po) which was the standard. Pretreatment with ENO (10, 30, and 100 mg/kg)
      and propranolol for 2 weeks followed by ISO challenge in rats prevented the
      elevation of marker enzymes such as lactate dehydrogenase (LDH), gamma-glutamyl
      transferase (GGT), creatine kinase (CK-MB and creatine phosphokinase [CPK]),
      aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline
      phosphatase (ALP) in plasma. In addition, pretreatment with ENO and propranolol
      significantly attenuated the lipid peroxidation by maintaining the levels of
      enzymatic (superoxide dismutase and glutathione peroxidase) and nonenzymatic
      antioxidants (reduced glutathione and nitrite), which was also confirmed
      histologically. Taken together, the current study indicates that the
      hydroalcoholic extract of N oleander Linn flowers aid in cardioprotection
      probably by improving the antioxidant defense system during experimental
      myocardial necrosis.

PMID- 21191139
TI  - Polyunsaturated fatty acid intakes and alpha-linolenic acid metabolism.

PMID- 21191140
TI  - Fish consumption and risk of stroke in Swedish women.
AB  - BACKGROUND: Epidemiologic studies of fish consumption in relation to risk of
      stroke have yielded inconsistent results. OBJECTIVE: In this study, we examined
      the association between fish consumption and stroke incidence in women. DESIGN:
      We analyzed data from a population-based prospective cohort of 34,670 women in
      the Swedish Mammography Cohort who were free of cardiovascular disease and cancer
      at baseline. Information on fish consumption was obtained by a self-administered
      questionnaire in 1997. Incident cases of stroke were ascertained from the Swedish
      Hospital Discharge Registry. We used Cox proportional hazards regression to
      estimate relative risks (RRs) and 95% CIs. RESULTS: Over a mean follow-up of 10.4
      y, we ascertained 1680 incident cases of stroke, including 1310 cerebral
      infarctions, 233 hemorrhagic strokes, and 137 unspecified strokes. Fish
      consumption was significantly inversely associated with risk of total stroke but
      not with cerebral infarction or hemorrhagic stroke. Compared with women in the
      lowest quintile of fish consumption (<1.0 serving of fish/wk), the multivariable
      RR of total stroke for women in the highest quintile (>3.0 servings of fish/wk)
      was 0.84 (95% CI: 0.71, 0.98; P for trend = 0.049). Consumption of lean fish but
      not of other fish types was inversely associated with risk of stroke. The
      multivariable RR of total stroke was 0.67 (95% CI: 0.49, 0.93; P for trend =
      0.07) for >=3 servings of lean fish/wk compared with that for no consumption.
      CONCLUSION: These results suggest that the consumption of fish, especially of
      lean fish, may reduce risk of stroke in women. This trial was registered at
      clinicaltrials.gov as NCT01127698.

PMID- 21191141
TI  - Evaluation of 2 methods for sodium intake assessment in cardiac patients with and
      without heart failure: the confounding effect of loop diuretics.
AB  - BACKGROUND: Twenty-four-hour urine collections are considered the optimal method
      for sodium intake assessment. Whether a diagnosis of heart failure (HF) or the
      use of loop diuretic (LD) therapy for HF compromises the validity of 24-h urine
      collections as a surrogate marker for sodium intake is unknown. OBJECTIVE: The
      objective was to determine the strength of association between 24-h urine
      collections and food records for sodium intake assessment in non-HF cardiac
      patients and in HF patients stratified by LD usage. DESIGN: Food records and 24-h
      urine collections were simultaneously completed for 2 consecutive days.
      Correlation coefficients and the Bland-Altman method of agreement described the
      relation between the techniques. RESULTS: Non-HF cardiac patients (n = 96; mean
      +/- SD age: 65 +/- 11 y), HF patients who were not taking an LD (n = 47; 62 +/-
      11 y), and HF patients who were taking an LD (n = 62; age: 60 +/- 12 y) were
      included. Correlation coefficients for sodium intake between food records and
      urine collections were r = 0.624 (P < 0.001) for non-HF cardiac patients and r =
      0.678 (P < 0.001) for HF patients who were not taking an LD. However, no
      significant association (r = 0.132, P = 0.312) was observed for HF patients who
      were taking LDs. The 95% limits of agreement between the non-HF cardiac patients
      and the HF patients who were not taking LDs were similar but were ~50% wider for
      HF patients who were taking LDs. CONCLUSIONS: For the assessment of sodium
      intake, food records agree well with 24-h urine collections in non-HF patients
      with cardiovascular disease and in HF patients who are not receiving LD but not
      for HF patients who are taking LDs. Therefore, food records may provide a better
      estimate of sodium intake in HF patients who are receiving LD therapy.

PMID- 21191142
TI  - Sodium content of processed foods in the United Kingdom: analysis of 44,000 foods
      purchased by 21,000 households.
AB  - BACKGROUND: In the United Kingdom, sodium reduction targets have been set for a
      large number of processed food categories. Assessment and monitoring are
      essential to evaluate progress. OBJECTIVES: Our aim was to determine whether
      household consumer panel food-purchasing data could be used to assess the sodium
      content of processed foods. Our further objectives were to estimate the mean
      sodium content of UK foods by category and undertake analyses weighted by food
      purchasing volumes. DESIGN: Data were obtained for 21,108 British households
      between October 2008 and September 2009. Purchasing data (product description,
      product weight, annual purchases) and sodium values (mg/100 g) were collated for
      all food categories known to be major contributors to sodium intake. Unweighted
      and weighted mean sodium values were calculated. RESULTS: Data were available for
      44,372 food products. The largest contributors to sodium purchases were table
      salt (23%), processed meat (18%), bread and bakery products (13%), dairy products
      (12%), and sauces and spreads (11%). More than one-third of sodium purchased
      (37%) was accounted for by 5 food categories: bacon, bread, milk, cheese, and
      sauces. For some food groups (bread and bakery, cereals and cereal products,
      processed meat), purchase-weighted means were 18-35% higher than unweighted
      means, suggesting that market leaders have higher sodium contents than the
      category mean. CONCLUSION: The targeting of sodium reduction in a small number of
      food categories and focusing on products sold in the highest volumes could lead
      to large decreases in sodium available for consumption and therefore to gains in
      public health.

PMID- 21191143
TI  - Bolus arginine supplementation affects neither muscle blood flow nor muscle
      protein synthesis in young men at rest or after resistance exercise.
AB  - The aim of this study was to investigate the ergogenic potential of arginine on
      NO synthesis, muscle blood flow, and skeletal muscle protein synthesis (MPS).
      Eight healthy young men (22.1 +/- 2.6 y, 1.79 +/- 0.06 m, 76.6 +/- 6.2 kg; mean
      +/- SD) participated in 2 trials where they performed a bout of unilateral leg
      resistance exercise and ingested a drink containing either 10 g essential amino
      acids with 10 g l-arginine (ARG) or an isonitrogenous control (CON). Femoral
      artery blood flow of both the nonexercised and exercised leg was measured
      continuously using pulsed-wave Doppler ultrasound, while rates of mixed and
      myofibrillar MPS were determined using a primed continuous infusion of L-[ring
      (13)C(6)] or L-[ring-(2)H(5)]phenylalanine. The plasma arginine concentration
      increased 300% during the ARG trial but not during the CON trial (P < 0.001).
      Plasma nitrate, nitrite, and endothelin-1, all markers of NO synthesis, did not
      change during either the ARG or CON trial. Plasma growth hormone increased to a
      greater degree after exercise in the ARG trial than CON trial (P < 0.05). Femoral
      artery blood flow increased 270% above basal in the exercised leg (P < 0.001) but
      not in the nonexercised leg, with no differences between the ARG and CON trials.
      Mixed and myofibrillar MPS were both greater in the exercised leg compared with
      the nonexercised leg (P < 0.001), but did not differ between the ARG and CON
      treatments. We conclude that an oral bolus (10 g) of arginine does not increase
      NO synthesis or muscle blood flow. Furthermore, arginine does not enhance mixed
      or myofibrillar MPS either at rest or after resistance exercise beyond that
      achieved by feeding alone.

PMID- 21191144
TI  - Detergent-free isolation and characterization of cholesterol-rich membrane
      domains from trans-Golgi network vesicles.
AB  - Cholesterol is an abundant lipid of the trans-Golgi network (TGN) and of certain
      endosomal membranes where cholesterol-rich microdomains are important in the
      organization and compartmentalization of vesicular trafficking. Here we describe
      the development of a rapid method to isolate a cholesterol-rich endomembrane
      fraction. We show that widely used subcellular fractionation techniques
      incompletely separate cholesterol-rich membranes, such as the TGN, from
      organelles, such as late endosomes and lysosomes. To address this issue, we
      devised a new subcellular fractionation scheme involving two rounds of velocity
      centrifugation, membrane sonication, and discontinuous sucrose density gradient
      centrifugation. This strategy resulted in the isolation of a cholesterol and GM1
      glycosphingolipid-enriched membrane fraction that was completely cleared of
      plasma membrane, endoplasmic reticulum, and mitochondria. This buoyant fraction
      was enriched for the TGN and recycling endosome proteins Rab11 and syntaxin-6,
      and it was well resolved from cis-Golgi and early and late endosomal membranes.
      We demonstrate that this technique can give useful insights into the
      compartmentation of phosphoinositide synthesis, and it facilitates the isolation
      of cholesterol-rich membranes from a population of TGN-trafficking vesicles.

PMID- 21191145
TI  - Polymorphisms associated with type 2 diabetes in familial longevity: The Leiden
      Longevity Study.
AB  - Human longevity is in part genetically determined, and the insulin/IGF-1 signal
      transduction (IIS) pathway has consistently been implicated. In humans, type 2
      diabetes is a frequent disease that results from loss of glucose homeostasis and
      for which new candidate polymorphisms now rapidly emerge from genome wide
      association studies. In the Leiden Longevity Study (n=2415), the offspring of
      long lived siblings ("offspring") who are genetically enriched for longevity were
      shown to have a more beneficial metabolic profile compared to their
      environmentally matched partners ("controls"), including better glucose
      tolerance. We tested whether the "offspring" carry a lower burden of diabetes
      risk alleles. Fifteen polymorphisms derived from genome wide association (GWA)
      scans in type 2 diabetes were tested for association with parameters of glucose
      metabolism in offspring and controls, and burden of risk alleles was compared
      between offspring and controls. Among all participants, a higher number of type 2
      diabetes risk alleles associated with a higher prevalence of diabetes (P=0.011)
      and higher serum concentration of glucose (P<0.016) but not insulin (P=0.450).
      None of the polymorphisms differed in frequency between the offspring and
      controls (all P>0.05), nor did the mean total number of risk alleles (P=0.977).
      The association between polymorphisms and glucose levels did not differ between
      controls and offspring (Pinteraction=0.523). The better glucose tolerance of the
      "offspring" is not explained by a lower burden of type 2 diabetes risk alleles,
      suggesting that specific mechanisms determining longevity exist.

PMID- 21191146
TI  - Phospho-DeltaNp63alpha/Rpn13-dependent regulation of LKB1 degradation modulates
      autophagy in cancer cells.
AB  - Oxidative stress was shown to promote the translocation of Ataxia-telangiectasia
      mutated (ATM) to cytoplasm and trigger the LKB1-AMPK-tuberin pathway leading to a
      down-regulation of mTOR and subsequently inducing the programmed cell death II
      (autophagy). Cisplatin was previously found to induce the ATM-dependent
      phosphorylation of DeltaNp63alpha in squamous cell carcinoma (SCC) cells. In this
      study, phosphorylated (p)-DeltaNp63alpha was shown to bind the ATM promoter, to
      increase the ATM promoter activity and to enhance the ATM cytoplasmic
      accumulation. P-DeltaNp63alpha protein was further shown to interact with the
      Rpn13 protein leading to a proteasome-dependent degradation of p-DeltaNp63alpha
      and thereby protecting LKB1 from the degradation. In SCC cells (with an altered
      ability to support the ATM-dependent DeltaNp63alpha phosphorylation), the non
      phosphorylated DeltaNp63alpha protein failed to form protein complexes with the
      Rpn13 protein and thereby allowing the latter to bind and target LKB1 into a
      proteasome-dependent degradation pathway thereby modulating a cisplatin-induced
      autophagy. We thus suggest that SCC cells sensitive to cisplatin-induced cell
      death are likely to display a greater ratio of p-DeltaNp63alpha/non
      phosphorylated DeltaNp63alpha than cells with the innate resistant/impaired
      response to a cisplatin-induced cell death. Our data also suggest that the choice
      made by Rpn13 between p-DeltaNp63alpha or LKB1 to be targeted for degradation is
      critical for cell death decision made by cancer cells in response to
      chemotherapy.

PMID- 21191147
TI  - Why the disposable soma theory cannot explain why women live longer and why we
      age.

PMID- 21191148
TI  - The DNA damage response: Balancing the scale between cancer and ageing.
AB  - Defects in the DNA damage response often lead to an increased susceptibility to
      cancer, and so the DDR presents an interesting set of novel therapeutic targets.
      The maintenance of genomic integrity by the DDR has also been found to be
      involved in the process of organismal ageing. While the removal of cells
      containing damaged DNA can be beneficial in the prevention of cancer, it may
      contribute to both normal and pathological ageing.

PMID- 21191150
TI  - Estimation of mean glandular dose for breast tomosynthesis: factors for use with
      the UK, European and IAEA breast dosimetry protocols.
AB  - A formalism is proposed for the estimation of mean glandular dose for breast
      tomosynthesis, which is a simple extension of the UK, European and IAEA protocols
      for dosimetry in conventional projection mammography. The formalism introduces t
      factors for the calculation of breast dose from a single projection and T-factors
      for a complete exposure series. Monte Carlo calculations of t-factors have been
      made for an imaging geometry with full-field irradiation of the breast for a wide
      range of x-ray spectra, breast sizes and glandularities. The t-factors show
      little dependence on breast glandularity and tables are provided as a function of
      projection angle and breast thickness, which may be used for all x-ray spectra
      simulated. The T-factors for this geometry depend upon the choice of projection
      angles and weights per projection, but various example calculations gave values
      in the range 0.93-1.00. T-factors are also provided for the Sectra tomosynthesis
      system, which employs a scanned narrow-beam imaging geometry. In this quite
      different configuration, the factor (denoted T(S)) shows an important dependence
      on breast thickness, varying between 0.98 and 0.76 for 20 and 110 mm thick
      breasts, respectively. Additional data are given to extend the current
      tabulations of g-, c- and s-factors used for dosimetry of conventional 2D
      mammography.

PMID- 21191149
TI  - Alterations of retinal pigment epithelium cause AMD-like retinopathy in
      senescence-accelerated OXYS rats.
AB  - Pathogenesis of age-related macular degeneration (AMD), the leading cause of
      blindness in the world, remains poorly understood. This makes it necessary to
      create animal models for studying AMD pathogenesis and to design new therapeutic
      approaches. Here we showed that retinopathy in OXYS rats is similar to human AMD
      according to clinical signs, morphology, and vascular endothelium growth factor
      (VEGF) and pigment epithelium-derived factor (PEDF) genes expression. Clinical
      signs of retinopathy OXYS rats manifest by the age 3 months against the
      background of significantly reduced expression level of VEGF and PEDF genes due
      to the decline of the amount of retinal pigment epithelium (RPE) cells and
      alteration of choroidal microcirculation. The disruption in OXYS rats' retina
      starts at the age of 20 days and appears as reduce the area of RPE cells but does
      not affect their ultrastructure. Ultrastructural pathological alterations of RPE
      as well as develop forms of retinopathy are observed in OXYS rats from age 12
      months and manifested as excessive accumulation of lipofuscin in RPE regions
      adjacent to the rod cells, whirling extentions of the basement membrane into the
      cytoplasm. These data suggest that primary cellular degenerative alterations in
      the RPE cells secondarily lead to choriocapillaris atrophy and results in
      complete loss of photoreceptor cells in the OXYS rats' retina by the age of 24
      months.

PMID- 21191151
TI  - Effects of optical beam angle on quantitative optical coherence tomography (OCT)
      in normal and surface degenerated bovine articular cartilage.
AB  - Quantitative measurement of articular cartilage using optical coherence
      tomography (OCT) is a potential approach for diagnosing the early degeneration of
      cartilage and assessing the quality of its repair. However, a non-perpendicular
      angle of the incident optical beam with respect to the tissue surface may cause
      uncertainty to the quantitative analysis, and therefore, significantly affect the
      reliability of measurement. This non-perpendicularity was systematically
      investigated in the current study using bovine articular cartilage with and
      without mechanical degradation. Ten fresh osteochondral disks were quantitatively
      measured before and after artificially induced surface degradation by mechanical
      grinding. The following quantitative OCT parameters were determined with a
      precise control of the surface inclination up to an angle of 10 degrees  using a
      step of 2 degrees : optical reflection coefficient (ORC), variation of surface
      reflection (VSR) along the surface profile, optical roughness index (ORI) and
      optical backscattering (OBS). It was found that non-perpendicularity caused
      systematic changes to all of the parameters. ORC was the most sensitive and OBS
      the most insensitive to the inclination angle. At the optimal perpendicular
      angle, all parameters could detect significant changes after surface degradation
      (p < 0.01), except OBS (p > 0.05). Nonsignificant change of OBS after surface
      degradation was expected since OBS reflected properties of the internal cartilage
      tissue and was not affected by the superficial mechanical degradation. As a
      conclusion, quantitative OCT parameters are diagnostically potential for
      characterizing the cartilage degeneration. However, efforts through a better
      controlled operation or corrections based on computational compensation mechanism
      should be made to minimize the effects of non-perpendicularity of the incident
      optical beam when clinical use of quantitative OCT is considered for assessing
      the articular cartilage.

PMID- 21191152
TI  - Comparative analysis of instance selection algorithms for instance-based
      classifiers in the context of medical decision support.
AB  - When constructing a pattern classifier, it is important to make best use of the
      instances (a.k.a. cases, examples, patterns or prototypes) available for its
      development. In this paper we present an extensive comparative analysis of
      algorithms that, given a pool of previously acquired instances, attempt to select
      those that will be the most effective to construct an instance-based classifier
      in terms of classification performance, time efficiency and storage requirements.
      We evaluate seven previously proposed instance selection algorithms and compare
      their performance to simple random selection of instances. We perform the
      evaluation using k-nearest neighbor classifier and three classification problems:
      one with simulated Gaussian data and two based on clinical databases for breast
      cancer detection and diagnosis, respectively. Finally, we evaluate the impact of
      the number of instances available for selection on the performance of the
      selection algorithms and conduct initial analysis of the selected instances. The
      experiments show that for all investigated classification problems, it was
      possible to reduce the size of the original development dataset to less than 3%
      of its initial size while maintaining or improving the classification
      performance. Random mutation hill climbing emerges as the superior selection
      algorithm. Furthermore, we show that some previously proposed algorithms perform
      worse than random selection. Regarding the impact of the number of instances
      available for the classifier development on the performance of the selection
      algorithms, we confirm that the selection algorithms are generally more effective
      as the pool of available instances increases. In conclusion, instance selection
      is generally beneficial for instance-based classifiers as it can improve their
      performance, reduce their storage requirements and improve their response time.
      However, choosing the right selection algorithm is crucial.

PMID- 21191153
TI  - Clinicians' perceptions of telemedicine for remote neonatal consultation.
AB  - Telemedicine may have a useful role in neonatal care, particularly in
      regionalised health care systems where there may be impediments to access.
      Following the development of a system for neonatal teleconsultation, we assessed
      its efficacy, usability and preliminary effectiveness. While results were
      positive, uptake in routine clinical use was less than expected. The study
      described in this paper examined aspects of clinicians' perceptions of
      telemedicine in neonatal care. Overall, clinicians had positive perceptions of
      telemedicine. Further work is required to understand the negative perceived
      usefulness of telemedicine held by some clinicians and to determine whether this
      may be overcome.

PMID- 21191154
TI  - Home telemedicine for paediatric palliative care.
AB  - Children with life limiting conditions require intensive, complex management of
      the physical, psychosocial and spiritual issues that evolve for the child and
      their family as the focus of care moves from curative treatment to palliation.
      Optimal palliative care for children can be limited by the lack of health
      professionals with the necessary skills and experience to confidently and
      competently manage the care of both the child and the family. The University of
      Queensland's Centre for Online Health has been working closely with the
      Paediatric Palliative Care Service (PPCS) at the Royal Children's Hospital (RCH)
      in Brisbane, Australia, to investigate the potential of telemedicine for the
      delivery of specialist support in the home or local community. Research conducted
      in Queensland has shown how telemedicine can be effectively used to link the
      specialist paediatric palliative care team into the home of families caring for a
      child receiving palliative care, regardless of their physical distance from the
      RCH. This qualitative report describes two case studies, each illustrating the
      value of home telemedicine for families at this vulnerable and distressing time.
      This work should provide a useful insight for other specialty disciplines
      contemplating home telemedicine applications.

PMID- 21191155
TI  - A literature review of email-based telemedicine.
AB  - A structured analysis of peer-reviewed literature about the delivery of health
      services by email was undertaken for this review. A total of 185 articles were
      included in the analysis. These articles were thematically categorised for
      medical specialty, participants, sub-topic, study design and service-delivery
      application. It was shown that email-based telemedicine can be practiced in a
      large number of medical specialties and has application in primary consultation,
      second opinion consultation, telediagnosis and administrative roles (e.g. e
      referral). Email has niche applications in low-bandwidth, image-based specialties
      (e.g. dermatology, pathology, wound care and ophthalmology) where attached
      digital camera images were used for telediagnosis. Diagnostic accuracy of these
      images was the predominant topic of research and results show email as a valid
      means of delivering these medical services. Email is also often used in general
      practice as an adjunct for face-to-face consultation. Further, a number of
      organisations have significantly improved the efficiency of their outpatient
      services when using email as a triage or e-referral system. Email-based
      telemedicine provides specialist medical opinion in the majority of reviewed
      services and is most likely to be instigated by the patient's primary care giver.
      However, email-consultations between patient and primary care and patient and
      secondary care are not uncommon. Most email services are implemented using
      ordinary email. However, a number of organisations have developed purpose-written
      email applications to support their telemedicine service due to impediments of
      using ordinary email. These impediments include lack of management tools for: the
      allocation and auditing of cases for a timely response and the co-ordination of
      effort in a multi-clinician, multi-disciplinary service. The ability to encrypt
      ordinary email thereby securing patient confidentiality is also regarded as
      difficult when using ordinary email. Hence, alternative web-based email
      applications where the encryption can be implemented using the more user-friendly
      HTTPS have become popular. Much of the reviewed literature is descriptive or
      anecdotal and hence, suffers from lack of conclusive results regarding positive
      patient outcomes. This may account for email-based telemedicine generally being
      regarded as underutilised. However, the potential is well recognised.

PMID- 21191156
TI  - A transmission security framework for email-based telemedicine.
AB  - Encryption is used to convert an email message to an unreadable format thereby
      securing patient privacy during the transmission of the message across the
      Internet. Two available means of encryption are: public key infrastructure (PKI)
      used in conjunction with ordinary email and secure hypertext transfer protocol
      (HTTPS) used by secure web-mail applications. Both of these approaches have
      advantages and disadvantages in terms of viability, cost, usability and
      compliance. The aim of this study was develop an instrument to identify the most
      appropriate means of encrypting email communication for telemedicine. A multi
      method approach was used to construct the instrument. Technical assessment and
      existing bodies of knowledge regarding the utility of PKI were analyzed, along
      with survey results from users of Queensland Health's Child and Youth Mental
      Health Service secure web-mail service. The resultant decision support model
      identified that the following conditions affect the choice of encryption
      technology: correspondent's risk perception, correspondent's identification to
      the security afforded by encryption, email-client used by correspondents, the
      tolerance to human error and the availability of technical resources. A decision
      support model is presented as a flow chart to identify the most appropriate
      encryption for a specific email-based telemedicine service.

PMID- 21191157
TI  - Readiness of nurses for practicing telehealth.
AB  - Nurses represent the largest group of healthcare professionals; and their role in
      healthcare is diverse. The lack of nurses in the workforce and the increasing
      demand of care continues to challenge health systems across the globe. Telehealth
      has been identified as a potential alternative method for delivering health
      services. Evidence is emerging that the use of telehealth by nurses results in
      efficiency gains and cost effective health care delivery. Regardless of growing
      evidence, the use of telehealth in nursing practice is still very limited. The
      lack of systematic education programs in telehealth and the lack of resilience in
      regards to organisational change remain significant barriers for the uptake of
      telehealth for nurses.

PMID- 21191158
TI  - Wearable dry sensors with bluetooth connection for use in remote patient
      monitoring systems.
AB  - Cost reduction has become the primary theme of healthcare reforms globally. More
      providers are moving towards remote patient monitoring, which reduces the length
      of hospital stays and frees up their physicians and nurses for acute cases and
      helps them to tackle staff shortages. Physiological sensors are commonly used in
      many human specialties e.g. electrocardiogram (ECG) electrodes, for monitoring
      heart signals, and electroencephalogram (EEG) electrodes, for sensing the
      electrical activity of the brain, are the most well-known applications.
      Consequently there is a substantial unmet need for physiological sensors that can
      be simply and easily applied by the patient or primary carer, are comfortable to
      wear, can accurately sense parameters over long periods of time and can be
      connected to data recording systems using Bluetooth technology. We have developed
      a small, battery powered, user customizable portable monitor. This prototype is
      capable of recording three-axial body acceleration, skin temperature, and has up
      to four bio analogical front ends. Moreover, it is also able of continuous
      wireless transmission to any Bluetooth device including a PDA or a cellular
      phone. The bio-front end can use long-lasting dry electrodes or novel textile
      electrodes that can be embedded in clothes. The device can be powered by a
      standard mobile phone which has a Ni-MH 3.6 V battery, to sustain more than seven
      days continuous functioning when using the Bluetooth Sniff mode to reduce TX
      power. In this paper, we present some of the evaluation experiments of our
      wearable personal monitor device with a focus on ECG applications.

PMID- 21191159
TI  - Ambulatory stress monitoring with a wearable bluetooth electrocardiographic
      device.
AB  - We tried to monitor stress by using a wearable one channel ECG device that can
      send ECG signals through Bluetooth wireless communication. Noxious physical and
      mental arithmetic stress was given three times repeatedly to healthy adults, and
      cortisol and catecholamines were measured serially from peripheral blood. At the
      same time, time domain and frequency domain parameters of heart rate variability
      (HRV) were calculated by taking precordial electrocardiogram. The intensity of
      correlation between subjective visual analogue scale (VAS) and catecholamine,
      cortisol, and HRV parameters according to stress was analyzed by using
      concordance correlation coefficients. The HRV triangular index and LF/HF ratio
      had high concordance correlation with the degree of stress in the physical stress
      model. In mental arithmetic stress model, the HRV triangular index and LF/HF
      ratio had weak concordance correlation with the degree of stress, and it had
      lower predictability than epinephrine. In both models, cortisol had some
      correlation with catecholamine, but it had little correlation with HRV
      parameters. HRV parameters using wearable one channel ECG device can be useful in
      predicting acute stress and also in many other areas.

PMID- 21191160
TI  - Considering the socio-cultural impact of e-health.
AB  - e-Health projects are being implemented globally in low-income countries as a
      response to the identified inequality and inequity of access to health services
      for poor populations with a great burden of disease. These projects are seen to
      offer solutions that provide quality care at a low cost. Limited research is done
      on the sustainability of these projects. Even less addresses the socio-cultural
      impact on the host communities. Based on experience of living with a remote
      community in Ghana, this paper explores the needs of one community, and how e
      Health has the ability to meet those needs using different solutions. Also
      examined are the potential positive and negative impacts that e-Health might
      yield on the people and their surroundings were e-health solutions to be
      introduced.

PMID- 21191161
TI  - Feasibility of a mobile anticoagulation telemedicine system using automated
      decision support.
AB  - Anticoagulation is necessary for many patients after implantation of mechanical
      heart valves. In order to reduce the number of visits to a physician for the
      review of INR values, we propose a telemedicine system based on mobile phones for
      patients and physicians. Physicians are furthermore supported by a decision
      support system offering recommendations for therapy adjustments.

PMID- 21191162
TI  - An overview of the national telehealth initiative in Malaysia.
AB  - Malaysia's national health statistics for the last half century show a remarkable
      improvement in the nation's health status. One important factor for this
      improvement is the Malaysian government's proactive intervention in the health
      sector. Among others, e-health has played a vital role in delivering and managing
      healthcare services in Malaysia. While the Government has integrated telehealth
      in its national digital infrastructure re-design, it has heavily invested in
      telehealth. The enactment of new laws to facilitate telehealth practices can also
      be noted as an important measure.

PMID- 21191163
TI  - Telehealth or Tele-education? Providing intensive, ongoing therapy to remote
      communities.
AB  - The Royal Institute for Deaf and Blind Children (RIDBC) in Sydney, Australia has
      demonstrated an ongoing commitment to innovation in the field of hearing
      impairment. RIDBC has created a unique program known as RIDBC Teleschool which
      successfully utilises videoconferencing technology to provide specialist hearing
      support and associated therapies to children living in rural and remote areas of
      Australia, including children in Indigenous communities. The high rate of hearing
      loss in Indigenous communities has led to the implementation of hearing screening
      programs in many areas of Australia. However, access to therapy support after
      screening is a critical intervention component which is often lacking in
      screening programs. RIDBC Teleschool uses a telehealth model to address this
      unmet need.

PMID- 21191164
TI  - Tailoring teleconsultation to meet the current needs of neurosurgical services: a
      multimodality oriented neurosurgical consultation.
AB  - Teleconsultation in Neurosurgery was introduced in Malaysia in 2006 with the aims
      of enhancing quality services in the field of Neurosurgery. The present
      teleconsultation system is equipped with user friendly features which allow
      physicians to send and neurosurgeons to gain access to patient data in a swift
      and effective manner. In the past, teleconsultation in neurosurgery was tied with
      teleradiology, however we have now developed a multimodality system to cater
      specifically for neurosurgery. In Malaysia, the teleconsultation service is
      gaining momentum as evidenced by the large volume of cases channeled through this
      system. 944 cases within a span of 4 months were recorded on the system. 54.5% of
      the cases were trauma, 33.2% stroke, 6.1% intracranial tumours, 2% of cases were
      of spinal pathology, 2% pediatric anomalies and 2.2% intracranial infections.
      50.2% of the referrals were after regular working hours reflecting the need for
      dedicated teleneurosurgery consultative services and the ability to review
      referrals outside of hospitals. Only 36% of cases needed emergency transfers and
      9.9% of the cases were managed remotely at distant hospitals. Another 9.4% of the
      cases were either transferred electively or brought to the clinic for
      consultation. The above findings emphasise the importance of teleconsultation as
      a means to provide wide medical coverage within the region.

PMID- 21191165
TI  - Foundations in global e-health: a global capacity building course.
AB  - The "Foundations in Global e-Health" is a capacity building initiative designed
      for providers, managers, and ICT professionals in the healthcare sector.
      Currently being trialled through PANACeA (a pan-Asian e-health research network)
      it is intended to offer the course in other developing regions from 2011. Using
      adult education principles, this on-line, self-paced course is offered in a
      modular fashion comprising 12 modules; the workload of each module is in the
      range of 20-24 hrs, with modules 2 to 12 requiring 1 month for completion. The
      evidence-based curriculum is designed to provide an introduction to e-Health such
      that graduates of the program have a solid and standardised baseline awareness
      and understanding--a common foundation--from which they are better able to
      collaboratively communicate and independently develop and assess e-Health
      initiatives within their respective settings and countries.

PMID- 21191166
TI  - Healthy e-health? Think 'environmental e-health'!
AB  - The Environmental e-Health Research and Training Program has completed its
      scoping study to understand the breadth of a new field of research: Environmental
      e-Health. Nearly every aspect of modern life is associated, directly or
      indirectly, with application of technology, from a cup of coffee, through
      transportation to and from work, to appliances in the home and industrial
      activities. In recent decades the rapidly increasing application of information
      and communications technologies (ICT) has added to the cacophony of technological
      'noise' around us. Research has shown that technology use, including ICTs, has
      impact upon the environment. Studying environmental impact in such a complex
      global setting is daunting. e-Health is now being used as a convenient microcosm
      of ICT application within which to study these impacts, and is particularly
      poignant given that e-Health's environmental harms conflict with its noble goals
      of 'doing no harm'. The study has identified impacts, both benefits and harms in
      all three life-cycle phases for e-Health: up-stream (materials extraction,
      manufacturing, packaging, distribution), mid-stream (use period), and down-stream
      (end-of-life processes--disposal, recycling). In addition the literature shows
      that a holistic 'Life Cycle Assessment' approach is essential to understand the
      complexity of the setting, and determine the true balance between total harms and
      total benefits, and for whom.

PMID- 21191167
TI  - Home telecare study for patients with chronic lung disease in the Sydney West
      Area Health Service.
AB  - Information and communication technologies may be used to provide health care
      services to people living at home. The term "home telecare" has been coined for
      this service. The elderly and patients with chronic pulmonary conditions, heart
      disease and diabetes have been thought to be obvious beneficiaries. The evidence
      base supporting home telecare is growing; however, there is a need for studies of
      long-term deployment and integration with existing health system processes. We
      discuss the experiences gained from one such pilot conducted in the Sydney West
      Area Health Service, which examines the integration of home telecare within the
      framework of an existing respiratory ambulatory care service. Interim results
      demonstrate high levels of reliability and positive patient attitude towards use
      of home monitoring. Clinical staff acceptance levels appeared lower. Effects on
      health burden, such as hospital admissions and nurse workload, were not
      significantly altered. The study results have been essential in developing local
      telecare knowledge within the health care community.

PMID- 21191168
TI  - Clinical services and professional support: a review of mobile telepaediatric
      services in Queensland.
AB  - In Queensland, the majority of rural hospitals and some regional hospitals lack
      paediatricians or paediatric sub-specialists. Many specialist referrals result in
      a transfer to a tertiary paediatric hospital in Brisbane--up to 3000 km away.
      Travel is difficult, time-consuming and expensive, especially from rural and
      remote areas in Queensland. The telepaediatric service managed by the Centre for
      Online Health (COH) at the Royal Children's Hospital (RCH) in Brisbane, delivers
      general and specialist paediatric support directly into selected neonatal and
      paediatric wards in a convenient and child-friendly manner. We conducted a review
      of telepaediatric service records to determine which clinical and educational
      services had been delivered through the mobile videoconference systems.
      Telepaediatric service activity records for all consultations conducted between
      January 2005 and July 2010 were summarised.Since 2005, seven mobile
      telepaediatric systems have been established in selected regional hospitals
      throughout Queensland. For some hospitals, the service was used mainly for
      consultations with specialists based at the RCH or at The Townsville Hospital
      (TTH) in north Queensland. During a 67 month period, a total of 966 consultations
      were conducted during 465 videoconference sessions, totaling about 228 hours of
      activity. In addition, 39 education sessions were delivered to regional staff
      through the mobile robot systems by specialists based at the RCH in Brisbane. The
      telepaediatric robots have proven useful for general paediatric support for
      hospitals without a local paediatrician; sub-specialist paediatric support and
      professional education and support for regional clinicians. Our service model
      provided a streamlined method of delivering specialist health services to
      children and families living in rural and remote regions of Queensland.

PMID- 21191169
TI  - Coalescing medical systems: a challenge for health informatics in a global world.
AB  - As globalisation advances, patients in many nations increasingly access diverse
      medical systems including Western medicine, Traditional Chinese Medicine,
      Homeopathy and Ayervedic medicine. The trend toward co-existence of medical
      systems presents challenges for health informatics including the need to develop
      standards that can encompass the diversity required, the need to develop software
      applications that effectively inter-operate across diverse systems and the need
      to support patients when evaluating competing systems. This article advances the
      notion that the challenges can most effectively be met with the development of
      informatics approaches that do not assume the superiority of one medical system
      over another. Argument visualization to support patient decision making in
      selecting an appropriate medical system is presented as an application that
      exemplifies this stance.

PMID- 21191170
TI  - Time-based interactive visualisation of vital signs.
AB  - Physiological vital signs are important factors for clinical processes like tele
      assessment, tele-monitoring and tele-treatment of patients. Records of patient
      vital signs over time are complex to understand without proper visualisation and
      data analysis aids. We present a model for interactively visualising vital signs
      in patient data histories, as used for remote chronic disease management. Our
      model allows simultaneous access to all vital signs records for the patient along
      a time-based axis. Clinicians and other health carers can then apply
      generalisation and refinement 'lenses' in a multi-layering visualisation
      mechanism to examine records further over single or multiple time sessions. The
      model also includes rule-based decisions for issuing notifications, when expected
      limits are exceeded.

PMID- 21191171
TI  - Using mobile phones for rapid reporting of zoonotic diseases in rural South
      Africa.
AB  - Human health is inextricably linked to animal health and production, particularly
      in developing regions of the world where animals play an important role in
      communities by providing transportation and food. Many deaths occur each year
      from a number of well-known and preventable animal diseases that are transmitted
      to humans, especially in developing countries, due to a lack of early detection
      and preventative measures. Despite the link between human health and animal
      health, veterinary telehealth has not attracted much attention from researchers
      in the medical health community. This paper describes a case study exploring the
      use of mobile phones for rapid reporting of zoonotic diseases in South Africa. It
      outlines an SMS-based mobile service to enable community members to report
      suspected cases of diseases. This service aims to increase the number and density
      of traditional reporting sources to facilitate near real-time reporting and
      consequently more rapid response to zoonoses outbreaks. The initial phases of
      this system design are described in addition to future directions.

PMID- 21191172
TI  - A qualitative study of sustainability and vulnerability in Australian telehealth
      services.
AB  - The uptake of telehealth into the ongoing and routine operations of healthcare
      has been slow, uneven and fragmented. Research has focused on the initial
      adoption and diffusion of telehealth, with much less known about sustainability.
      This study made a qualitative inquiry into the sustainability of a diverse sample
      of ceased and continuing telehealth services in Australia, asking why services
      ceased, and how continuing services were either vulnerable or sustainable. Fifty
      four Australian telehealth services were identified in the academic literature
      over a ten year period between 1998 and 2007. A sample of these was chosen for
      maximum variation, and 36 semi-structured interviews were conducted concerning 35
      telehealth services. Of these services, 8 had ceased, 14 were vulnerable, 10
      sustainable, and 3 could not be classified. The major theme from ceased services
      was lack of support and insufficient demand from participating sites.
      Vulnerabilities identified from operating sites were reliance on a single person,
      low levels of interest, short-term funding, and difficulties making the
      transition from research to service. Sustainable services had two main models of
      functioning: to reach a sufficient size and flow of referrals to justify
      dedicated staffing, coordination and infrastructure; or, to fit a lower level of
      telehealth activity into an existing clinical setting. Sustainability of
      telehealth services can be enhanced by choosing an operating model appropriate to
      the size of the service, meeting the needs of and developing good relationships
      with referring services, raising awareness, and succession planning.

PMID- 21191173
TI  - Plasminogen: A cellular protein cofactor for PrPSc propagation.
AB  - The biochemical essence of prion replication is the molecular multiplication of
      the disease-associated misfolded isoform of prion protein (PrP), termed PrPSc, in
      a nucleic acid-free manner. PrP(Sc) is generated by the protein misfolding
      process facilitated by conformational conversion of the host-encoded cellular PrP
      to PrP(Sc). Evidence suggests that an auxiliary factor may play a role in PrP(Sc)
      propagation. We and others previously discovered that plasminogen interacts with
      PrP, while its functional role for PrPSc propagation remained undetermined. In
      our recent in vitro PrP conversion study, we showed that plasminogen
      substantially stimulates PrP(Sc) propagation in a concentration-dependent manner
      by accelerating the rate of PrP(Sc) generation, while depletion of plasminogen,
      destabilization of its structure, and interference with the PrP-plasminogen
      interaction hinder PrP(Sc) propagation. Further investigation in cell culture
      models confirmed an increase of PrP(Sc) formation by plasminogen. Although
      molecular basis of the observed activity for plasminogen remain to be addressed,
      our results demonstrate that plasminogen is the first cellular protein auxiliary
      factor proven to stimulate PrP(Sc) propagation.

PMID- 21191174
TI  - Costimulating epithelial gammadelta T cells.

PMID- 21191175
TI  - Trophinin-mediated cell adhesion induces apoptosis of human endometrial
      epithelial cells through PKC-delta.
AB  - Trophinin is an intrinsic membrane protein expressed in trophectoderm cells of
      embryos and in uterine epithelial cells. Trophinin potentially mediates apical
      cell adhesion at human embryo implantation sites through trophinin-trophinin
      binding in these two cell types. Trophinin-mediated cell adhesion activates
      trophectoderm cells for invasion, whereas the effect of adhesion on maternal side
      is not known. We show that addition of GWRQ peptide, a previously established
      peptide that mimics trophinin-mediated cell adhesion, to human endometrial
      epithelial cells expressing trophinin induces their apoptosis. FAS involvement
      was excluded, as GWRQ did not bind to FAS, and FAS knockdown did not alter GWRQ
      induced apoptosis. Immunoblotting analyses of protein kinases revealed an
      elevation of PKC-d protein in GWRQ-bound endometrial epithelial cells. In the
      absence of GWRQ, PKC-d associated with trophinin and remained cytoplasmic, but
      after GWRQ binding to the trophinin extracellular domain, PKC-d became tyrosine
      phosphorylated, dissociated from trophinin, and entered the nucleus. In PKC-d
      knockdown endometrial cells, GWRQ did not induce apoptosis.

PMID- 21191176
TI  - Substrate-specific regulation of ubiquitination by the anaphase-promoting
      complex.
AB  - By orchestrating the sequential degradation of a large number of cell cycle
      regulators, the ubiquitin ligase anaphase-promoting complex (APC/C) is essential
      for proliferation in all eukaryotes. The correct timing of APC/C-dependent
      substrate degradation, a critical feature of progression through mitosis, was
      long known to be controlled by mechanisms targeting the core APC/C-machinery.
      Recent experiments, however, have revealed an important contribution of substrate
      specific regulation of the APC/C to achieve accurate cell division. In this
      perspective, we describe different mechanisms of substrate-specific APC/C
      regulation and discuss their importance for cell division.

PMID- 21191177
TI  - Probing the complexity of miRNA expression across hematopoiesis.

PMID- 21191178
TI  - Rare BRCA1 haplotypes including 3'UTR SNPs associated with breast cancer risk.
AB  - Genetic markers identifying women at an increased risk of developing breast
      cancer exist, yet the majority of inherited risk remains elusive. While numerous
      BRCA1 coding sequence mutations are associated with breast cancer risk, BRCA1
      mutations account for less then 5% of breast cancer risk. Since 3' untranslated
      region (3'UTR) polymorphisms disrupting microRNA (miRNA) binding can be
      functional and can act as genetic markers of cancer risk, we tested the
      hypothesis that such polymorphisms in the 3'UTR of BRCA1 and haplotypes
      containing these functional polymorphisms may be associated with breast cancer
      risk. We sequenced the BRCA1 3'UTR from breast cancer patients to identify miRNA
      disrupting polymorphisms. We further evaluated haplotypes of this region
      including the identified 3'UTR variants in a large population of controls and
      breast cancer patients (n = 221) with known breast cancer subtypes and
      ethnicities. We identified three 3'UTR variants in BRCA1 that are polymorphic in
      breast cancer populations, and haplotype analysis including these variants
      revealed that breast cancer patients harbor five rare haplotypes not generally
      found among controls (9.50% for breast cancer chromosomes, 0.11% for control
      chromosomes, p = 0.0001). Three of these rare haplotypes contain the rs8176318
      BRCA1 3'UTR functional variant. These haplotypes are not biomarkers for BRCA1
      coding mutations, as they are found rarely in BRCA1 mutant breast cancer patients
      (1/129 patients = 0.78%). These rare BRCA1 haplotypes and 3'UTR SNPs may
      represent new genetic markers of breast cancer risk.

PMID- 21191180
TI  - The NFkappaB paradox: RelB induces and inhibits gene expression.

PMID- 21191179
TI  - Downregulation of uPAR inhibits migration, invasion, proliferation, FAK/PI3K/Akt
      signaling and induces senescence in papillary thyroid carcinoma cells.
AB  - Papillary thyroid carcinoma (PTC) is the most common endocrine and thyroid
      malignancy.  The urokinase plasminogen activator receptor (uPAR) plays an
      important role in cancer pathogenesis, including breakdown of the extracellular
      matrix, invasion, and metastasis.  Additionally, there is increasing evidence
      that uPAR also promotes tumorigenesis via the modulation of multiple signaling
      pathways.  BRAFV600E, the most common initial genetic mutation in PTC, leads to
      ERK1/2 hyperphosphorylation, which has been shown in numerous cancers to induce
      uPAR.  Treatment of the BRAFV600E-positive PTC cell line, BCPAP, with the MEK/ERK
      inhibitor U0126 reduced uPAR RNA levels by 90%.  siRNA-mediated down-regulation
      of uPAR in BCPAP cells resulted in greatly decreased activity in the focal
      adhesion kinase (FAK)/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway.
      This phenomenon was concurrent with drastically reduced proliferation rates and
      decreased clonigenic survival, as well as demonstrated senescence-associated
      nuclear morphology and induction of b-galactosidase activity. uPAR-knockdown
      BCPAP cells also displayed greatly reduced migration and invasion rates, as well
      as a complete loss of the cells' ability to augment their invasiveness following
      plasminogen supplementation. Taken together, these data provide new evidence of a
      novel role for uPAR induction (as a consequence of constitutive ERK1/2
      activation) as a central component in PTC pathogenesis, and highlight the
      potential of uPAR as a therapeutic target.

PMID- 21191182
TI  - CD47 applies the brakes to angiogenesis via vascular endothelial growth factor
      receptor-2.

PMID- 21191181
TI  - Context-dependent regulation of Musashi-mediated mRNA translation and cell cycle
      regulation.
AB  - Musashi-mediated mRNA translational control has been implicated in the promotion
      of physiological and pathological stem cell proliferation. During self-renewal of
      mammalian stem cells, Musashi has been proposed to act to repress the translation
      of mRNAs encoding inhibitors of cell cycle progression. By contrast, in maturing
      Xenopus oocytes Musashi activates translation of target mRNAs that encode
      proteins promoting cell cycle progression. The mechanisms directing Musashi to
      differentially control mRNA translation in mammalian stem cells and Xenopus
      oocytes is unknown. In this study, we demonstrate that the mechanisms defining
      Musashi function lie within the cellular context. Specifically, we show that
      murine Musashi acts as an activator of translation in maturing Xenopus oocytes
      while Xenopus Musashi functions as a repressor of target mRNA translation in
      mammalian cells. We further demonstrate that within the context of a primary
      mammalian neural stem/progenitor cell, Musashi can be converted from a repressor
      of mRNA translation to an activator of translation in response to extracellular
      stimuli. We present current models of Musashi-mediated mRNA translational control
      and discuss possible mechanisms for regulating Musashi function. An understanding
      of these mechanisms presents exciting possibilities for development of
      therapeutic targets to control physiological and pathological stem cell
      proliferation.

PMID- 21191183
TI  - Menin controls the concentration of retinoblastoma protein.
AB  - Menin, the protein encoded by the Multiple Endocrine Neoplasia type 1 gene, is
      involved in the cell cycle control through its participation in functional
      dynamics of chromatin and regulation of transcription. RB, the protein of the
      retinoblastoma gene RB1, controls the progression of the cell cycle and is
      regulated in its activity by means of a feedback by phosphorylation. Studies in
      double heterozygous knockout mice for Men1 and the Retinoblastoma gene Rb1 have
      recently indicated that both genes may be implicated in the same pathways. In the
      course of our studies on Menin, we found that after suppression or in absence of
      Menin, RB1 expression was strongly reduced in a posttranscriptional manner. Under
      conditions of growth arrest, the hyperphosphorylated form of RB was most strongly
      affected, whereas its hypophosphorylated form was less or not at all reduced. Our
      findings confirm the hypothesis that the pathways of two tumor suppressor genes
      are connected.

PMID- 21191184
TI  - DNA-RNA hybrids contribute to the replication dependent genomic instability
      induced by Omcg1 deficiency.
AB  - During S phase, the replisome has to overcome many physical obstacles that can
      cause replication fork stalling and compromise genome integrity. Transcription is
      an important source of replicative stress and consequently, maintenance of genome
      integrity requires the protection of chromosomes from the deleterious effects
      arising from the interaction between nascent RNAs and template DNA, leading to
      stable DNA-RNA hybrids (R-loop) formation. We previously reported the essential
      role of Omcg1 (Ovum Mutant Candidate Gene) for cell cycle progression during
      early embryonic development. Here, we show that OMCG1 is a target of the cell
      cycle checkpoint kinases ATR/ATM and is essential for S phase progression in
      mouse embryonic fibroblasts. Using a conditional gene inactivation strategy, we
      demonstrate that OMCG1 depletion impairs cell viability as a consequence of DSB
      formation, checkpoint activation and replication fork collapse. We also show that
      no chromosome breaks were generated in non-cycling Omcg1-deficient cells.
      Furthermore, increased RNaseH expression significantly alleviated genomic
      instability in deficient fibroblasts suggesting that cotranscriptional R-loops
      formation contributes to the genesis of replication-dependent DSBs in these
      cells. Together with recent reports describing its participation to complexes
      involved in cotanscriptional processes, our results suggest that OMCG1 plays a
      role in the tight coupling between mRNA processing pathways and maintenance of
      genome integrity during cell cycle progression.

PMID- 21191186
TI  - Chemical states of the N-terminal "lid" of MDM2 regulate p53 binding: simulations
      reveal complexities of modulation.
AB  - Phosphorylation of S17 in the N-terminal "lid" of MDM2 (residues 1-24) is
      proposed to regulate the binding of p53. The lid is composed of an intrinsically
      disordered peptide motif that is not resolved in the crystal structure of the
      MDM2 N-terminal domain. Molecular dynamics simulations of MDM2 provide novel
      insight into how the lid undergoes complex dynamics depending on its
      phosphorylation state that have not been revealed by NMR analyses. The difference
      in charges between the phosphate and the phosphomimetic 'Asp' and the change in
      shape from tetrahedral to planar are manifested in differences in strengths and
      durations of interactions that appear to modulate access of the binding site to
      ligands and peptides differentially. These findings unveil the complexities that
      underlie protein-protein interactions and reconcile some differences between the
      biochemical and NMR data suggesting that lid mutation or deletion can change the
      specific activity of MDM2 and provide concepts for future approaches to evaluate
      the effects of S17 modification on p53 binding.

PMID- 21191185
TI  - Quantitative evidence for early life fitness defects from 32 longevity-associated
      alleles in yeast.
AB  - Reduced fecundity has been associated with some alleles that enhance longevity in
      invertebrate and mammalian models. This observation has been suggested to support
      the antagonistic pleiotropy theory of aging, which predicts that alleles of some
      genes promoting fitness early in life have detrimental effects later in life that
      limit survival. In only a few cases, however, has the relative fitness of long
      lived mutants been quantified through direct competition with the wild type
      genotype. Here we report the first comprehensive analysis of longevity/fitness
      trade-offs by measuring the relative fitness of 49 long-lived yeast variants in a
      direct competition assay with wild type cells. We find that 32 (65%) of these
      variants show a significant defect in fitness in this competition assay. In 26
      (81%) of these cases, this reduction in fitness can be partially accounted for by
      reduced maximal growth rate during early life, usually resulting from a G0/G1
      specific cell cycle defect. A majority of the less fit longevity-enhancing
      variants are associated with reduced mRNA translation. These findings are
      therefore consistent with the idea that enhanced longevity often comes with a
      fitness cost and suggest that this cost is often associated with variation in a
      subset of longevity factors, such as those regulating mRNA translation, growth,
      and reproduction.

PMID- 21191187
TI  - Could TCTP contribute to Armin Braun's paradigm of tumor reversion in plants?

PMID- 21191188
TI  - Curcumin: a component of the golden spice, targets multiple angiogenic pathways.

PMID- 21191191
TI  - Does the duration of a scholarly concentration affect medical students'
      productivity?

PMID- 21191189
TI  - Cancer-stromal interactions: role in cell survival, metabolism and drug
      sensitivity.
AB  - It has been known for a long time that the interaction between cancer cells and
      tissue microenvironment plays a major role in cancer development, progression and
      metastasis. The biochemical aspect of cancer-stromal interactions, however, is
      less appreciated. This short review article first provides a brief summary of the
      communications between cancer cells and the tissue microenvironment by direct
      cell-cell interactions and by soluble factors, and then describes several
      biochemical pathways that are important for the interaction between stromal and
      cancer cells with respect to energy metabolism, redox balance, cell survival and
      drug resistance. The potential therapeutic implications of abolishing stromal
      protective mechanisms to overcome drug resistance are also discussed.

PMID- 21191193
TI  - Caution needed when predicting problem residents.

PMID- 21191196
TI  - Residents' perceptions of their competence in end-of-life care: suggestions for
      further research.

PMID- 21191198
TI  - Patient safety education should start in the preclinical years.

PMID- 21191200
TI  - Commentary: Building the evidence base in support of the American Board of
      Medical Specialties maintenance of certification program.
AB  - In this issue, Lipner and colleagues describe research supporting the value of
      the examinations used in the maintenance of certification (MOC) programs of the
      American Board of Internal Medicine and the American Board of Surgery. The
      authors of this commentary review the contribution of this research and previous
      investigations that underscore the value of this component of the American Board
      of Medical Specialties (ABMS) MOC program. In addition, they point out that the
      MOC examination is one element of a comprehensive approach to physician lifelong
      learning, assessment, and quality improvement. The ABMS MOC program requires
      diplomates of the ABMS member boards to engage in continuous professional
      development in the six domains of competence and performance previously defined
      by the ABMS and the Accreditation Council for Graduate Medical Education.
      Although evidence and a sound rationale exist to support educational and
      assessment methods that target all six domains, it will be important to continue
      to build the body of evidence demonstrating the value of MOC to the public and to
      the profession.

PMID- 21191201
TI  - Commentary: Lowly interns, more is merrier, and the Casablanca Strategy.
AB  - Test ordering is an integral part of clinical decision making. Variation in test
      ordering behavior appears to reflect uncertainty in the clinical reasoning and
      decision-making process. Among decision makers, novices function mostly in the
      analytic mode of reasoning, experiencing high levels of uncertainty and,
      therefore, account for the most variance. While less discriminate test ordering
      has both economical and clinical downsides, it nevertheless remains a rite of
      passage along the road toward expertise. In response to the article by Iwashyna
      and colleagues, the author of this commentary reflects on the implications of
      test-ordering behavior in the academic medicine setting. The process of ordering
      tests can serve purposes other than the obvious, not the least of which allows
      the decision maker additional time for reflection in the decision-making process,
      perhaps leading to a less mindless and more mindful approach. The author observes
      that test-ordering behavior of novitiates might be optimized through a variety of
      strategies that improve both active and passive learning in the clinical
      environment. In addition to specific education around costs, as well as Bayesian
      considerations, active learning importantly requires exposure to those processes
      that may subvert clinical reasoning, notably cognitive biases. Passive learning
      is enhanced in supportive environments. Throughout, those who supervise and teach
      should provide effective models.

PMID- 21191202
TI  - Commentary: The RIME/EMR scheme: an educational approach to clinical
      documentation in electronic medical records.
AB  - Electronic medical records (EMRs) increasingly are used to document the delivery
      of patient care. Clinical practices that are involved in medical education are
      more likely to employ EMRs. Yet, the growing use of EMRs presents a new set of
      challenges for undergraduate and graduate medical education. EMRs can
      significantly impact how trainees learn and develop medical decision-making
      strategies and clinical documentation skills. EMRs also affect how clinical notes
      are evaluated and how feedback is provided to the learner. To use EMRs
      effectively, students must learn how narrative elements (how to take and record a
      medical history and physician examination), data elements (laboratory, radiology,
      medication, and information from ancillary and consultative services), and system
      elements (how EMRs function within the context of the health care or hospital
      system where the student trains) combine in the context of compassionate,
      competent, and safe patient care. This commentary specifically addresses
      educational issues surrounding student and resident use of EMR systems. The
      Reporter-Interpreter-Manager-Educator scheme is one approach to teach and
      evaluate clinical documentation skills using EMRs in the context of the
      Accreditation Council for Graduate Medical Education core educational
      competencies.

PMID- 21191203
TI  - The moral of the story.

PMID- 21191204
TI  - Artist's statement: Sleeping beauty.

PMID- 21191206
TI  - Medicine and the arts. Self-portrait with Dr. Arrieta by Francisco Jose de Goya y
      Lucientes. Commentary.

PMID- 21191207
TI  - Year of pain, year of promise.

PMID- 21191208
TI  - Lessons learned in Reno.

PMID- 21191209
TI  - Historical perspective.

PMID- 21191211
TI  - Putting patients first.

PMID- 21191212
TI  - Putting patients first.

PMID- 21191215
TI  - Educating charge nurses.

PMID- 21191217
TI  - Misleading nurses.

PMID- 21191218
TI  - The top health care news story of 2010: health insurance dominated the year.

PMID- 21191224
TI  - Under fire: nursing degrees from for-profit institutions.

PMID- 21191226
TI  - What future for the Affordable Care Act?

PMID- 21191230
TI  - Occupational hazards for pregnant nurses.
AB  - OVERVIEW: Depending on her working environment, specific immunities, and stage of
      pregnancy, a pregnant nurse may find it difficult to avoid teratogenic and
      fetotoxic exposures, as well as working conditions that could jeopardize her
      pregnancy. A clinical review of the occupational hazards faced by pregnant nurses
      can be useful to the concerned nurse or health care system, as can suggestions on
      ways to reduce risk and a list of pertinent occupational safety resources.

PMID- 21191232
TI  - Alcohol withdrawal during hospitalization.
AB  - OVERVIEW: For a chronic drinker, sudden alcohol withdrawal because of an
      unexpected hospitalization can lead to escalating withdrawal symptoms and even
      death if unrecognized and untreated. Nurses need to be aware of the prevalence of
      alcohol abuse in the United States and consider the possibility of unplanned
      alcohol withdrawal in their patients. This article discusses the effects on the
      body of chronic alcohol intake, the potential symptoms of alcohol withdrawal, and
      ways to recognize and treat these symptoms through early assessment and
      consistent intervention.

PMID- 21191236
TI  - Following the evidence: planning for sustainable change.

PMID- 21191234
TI  - Cultivating quality: Reducing the use of potentially inappropriate medications in
      older adults.

PMID- 21191237
TI  - Starting from scratch: training nurses in Afghanistan. Interview by Irene M
      Wielawski.

PMID- 21191245
TI  - Socks and all.

PMID- 21191246
TI  - Guide to nursing organizations.

PMID- 21191247
TI  - Specialty certification organizations. How to navigate specialty certifications.

PMID- 21191248
TI  - If life is the test, prepare yourself to ace it!

PMID- 21191250
TI  - How new graduates can gain a competitive edge.

PMID- 21191251
TI  - Volunteers make the difference.

PMID- 21191252
TI  - Examining the role of the forensic nurse death investigator.

PMID- 21191253
TI  - Your guide to certification. What you need to know to pursue professional
      recognition.

PMID- 21191254
TI  - Same-day surgery nursing: it takes teamwork.

PMID- 21191256
TI  - The Magnet(r) journey of a community hospital.

PMID- 21191257
TI  - Opportunity knocks for travel nurses.

PMID- 21191258
TI  - What's the state of interstate licensure?

PMID- 21191260
TI  - Low-dose aspirin for primary prevention of cardiovascular events in patients with
      diabetes: a meta-analysis.
AB  - INTRODUCTION: The use of low-dose aspirin for primary prevention of
      cardiovascular events in patients with diabetes is recommended by existing
      guidelines, but definitive evidence supporting its efficacy is lacking. The
      authors undertook a meta-analysis of published trials to determine the effect of
      low-dose aspirin for primary prevention of cardiovascular events in patients with
      diabetes. METHODS: Randomized controlled trials comparing low-dose aspirin versus
      placebo or no treatment in patients with diabetes (either exclusively or as a
      subgroup) with no previous history of cardiovascular disease were identified
      through MEDLINE and EMBASE databases. RESULTS: Seven randomized controlled trials
      met the inclusion criteria. Two studies included exclusively patients with
      diabetes, whereas the remaining 5 studies included patients with diabetes as a
      subgroup. Two studies were excluded because they did not provide diabetes
      specific data. Overall, aspirin was associated with a nonsignificant reduction in
      the hazard rate of the composite endpoint of major cardiovascular events compared
      with control (hazard ratio = 0.89, 95% confidence interval: 0.70-1.13, P = 0.33).
      Similarly, there was a nonsignificant reduction in the hazard rate of the
      individual endpoints of myocardial infarction, stroke, cardiovascular and all
      cause mortality. The risk of major bleeding increased nonsignificantly with
      aspirin compared with control (relative risk = 3.02, 95% confidence interval:
      0.48-18.86, P = 0.24). DISCUSSION: The role of low-dose aspirin for primary
      prevention of cardiovascular events in patients with diabetes remains unproven,
      and its routine use cannot be justified at present. More trials are needed to
      definitively address this issue.

PMID- 21191261
TI  - Relative resistance to oral theophylline treatment in patients with hyposmia
      manifested by decreased secretion of nasal mucus cyclic nucleotides.
AB  - INTRODUCTION: Oral treatment with the phosphodiesterase inhibitor theophylline in
      an open-label fixed-design clinical trial in 312 patients with hyposmia improved
      smell function in >50%. Before treatment, all patients had lower than normal
      levels of nasal mucus cAMP and cGMP. The purpose of this study was to study
      relationships among changes in smell function, theophylline levels and nasal
      mucus cAMP and cGMP among patients whose smell function improved (responders) and
      those who did not improve (nonresponders) on oral theophylline treatment.
      METHODS: After all data analysis from the clinical trial was completed, data from
      each of the 31 of the 312 patients in whom nasal mucus cAMP and cGMP and
      theophylline levels were available before and after theophylline treatment at
      several drug doses were evaluated. At initiation and at termination of each
      treatment, dose smell function, nasal mucus cAMP and cGMP and plasma theophylline
      were analyzed. RESULTS: On the same theophylline dose, although serum
      theophylline increased among both responders and nonresponders, serum levels were
      consistently higher among responders. Nasal mucus cAMP and cGMP were also higher
      among responders than nonresponders. At higher theophylline doses, cGMP reached
      normal levels among responders, whereas it did not change significantly among
      nonresponders. CONCLUSIONS: Some patients with hyposmia with initially low nasal
      mucus cAMP and cGMP levels may be relatively resistant to oral theophylline
      treatment. This result may offer a mechanism of response lack among some patients
      whose smell function did not improve after oral theophylline treatment although
      other factors may influence their response lack.

PMID- 21191262
TI  - Landmark Publication from The American Journal of the Medical Sciences:
      Macroscopic examination of the blood: discussion of its value and description of
      the use of a single instrument for the determination of sedimentation rate,
      volume of packed red cells, leukocytes and platelets, and of icterus index. 1933.

PMID- 21191263
TI  - It all started in New Orleans: Wintrobe, the hematocrit and the definition of
      normal.

PMID- 21191264
TI  - A case of disseminated intravascular coagulation associated with a prosthetic
      heart valve.
AB  - Malfunctioning prosthetic heart valves have been previously associated with
      nonimmune hemolytic anemia; however, disseminated intravascular coagulation has
      not previously been noted as a complication in the absence of infective
      endocarditis. The authors report the case of an 81-year-old woman who developed
      disseminated intravascular coagulation associated with a dysfunctional prosthetic
      heart valve.

PMID- 21191268
TI  - Current world literature.

PMID- 21191266
TI  - Current world literature.

PMID- 21191270
TI  - Mind-body medicine: lessons from a patient.

PMID- 21191271
TI  - Bibliography. Current world literature.

PMID- 21191272
TI  - The clinical impact of 2 different strategies for initiating therapy in patients
      with ocular hypertension.
AB  - PURPOSE: To assess the impact of 2 strategies for initiating therapy in ocular
      hypertension (OH) on drug use, intraocular pressure (IOP), and blindness caused
      by glaucoma. METHODS: Using a simulation model, initiating therapy with timolol
      (strategy 1) and with latanoprost (strategy 2) was simulated for a hypothetic
      cohort of ocular hypertension patients with an initial IOP distribution (data of
      1000 patients). Adjustment of therapy within 15 months and a subsequent lifelong
      follow-up, with an IOP dependent conversion to glaucoma, were modeled. The IOP
      lowering effect of medication (based on a meta-analysis) was applied by Monte
      Carlo simulation. Therapy could be maintained or changed, depending on the
      achieved IOP and side effects. Four drugs (latanoprost, timolol, brimonidine,
      dorzolamide) were used as monotherapy or in combination. Glaucoma conversion rate
      was based on literature. RESULTS: Treatment goal was achieved in both strategies
      in 90% by monotherapy. This was 60% for patients with initial IOP's of 30 mm Hg.
      The originally prescribed medication was maintained in 66% (1) and in 77% (2).
      IOP decreased with approximately 34%, from 25.4 mm Hg (mean) to 16.7 mm Hg (1)
      and to 16.5 mm Hg (2) Blindness per person within 18.7 years of life expectancy
      was 0.0923 years (1) and 0.0870 years (2), which corresponds to approximately 1
      month. The difference between strategies was 2 days spent in blindness per
      patient. CONCLUSIONS: The difference in clinical effects of the strategies is
      small. This is largely owing to the key concept of a target pressure, which
      underlies both strategies.

PMID- 21191274
TI  - Very deep sclerectomy.

PMID- 21191275
TI  - Endoscopic cyclophotocoagulation in osteo-odonto-keratoprosthesis (OOKP) eyes.

PMID- 21191277
TI  - Direct association between dietary cholesterol intake and blood pressure: too
      good to be 'entirely' true.

PMID- 21191278
TI  - Ambulatory blood pressure monitoring in diabetic patients: new data, new
      questions.

PMID- 21191279
TI  - Programmed 11beta-hydroxysteroid dehydrogenase type 2 reduction: a possible cause
      of adult-onset disease?

PMID- 21191280
TI  - Altered regulation of the epithelial sodium channel in hypertension. From genes
      to therapeutics.

PMID- 21191281
TI  - Does soy isoflavone extract improve blood pressure?

PMID- 21191284
TI  - Glaucoma: reporting back.

PMID- 21191285
TI  - Glaucoma: recent discoveries and patient care.

PMID- 21191287
TI  - In-vivo detection of the frequency and distribution of thin-cap fibroatheroma and
      ruptured plaques in patients with coronary artery disease: an optical coherence
      tomographic study.
AB  - OBJECTIVES: The purpose of this study was to assess the prevalence and to
      quantify the thin-cap fibroatheroma (TCFA) and ruptured plaques in patients with
      coronary artery disease using optical coherence tomography (OCT). BACKGROUND:
      TCFA lesions are the most prevalent precursors of plaque rupture, and are
      responsible for acute coronary syndromes (ACS). There are limited data regarding
      the frequency and distribution of TCFA in diseased coronary arteries. METHODS:
      Coronary artery OCT was performed in 78 vessels in 47 patients, with stable
      angina (SA) or ACS. OCT plaque characteristics were derived using criteria that
      had been validated earlier. TCFA was defined as rich in lipid (two or more
      quadrants) with thin fibrous cap (<65 MUm). Comparison was made between SA and
      unstable angina, and culprit and nonculprit vessels. RESULTS: There was a higher
      incidence of TCFA and plaque rupture (65 vs. 24%, P=0.003, and 40 vs. 15%,
      P=0.04) in ACS patients. This was reflected in a higher lipid pool (2.66 vs. 2.26
      quadrants, P=0.04) and minimum fibrous cap thickness (52 vs. 74 MUm, P=0.001) in
      ACS patients. The mean numbers of TCFA (2.5) were similar in patients with SA and
      ACS. However, the maximal length of TCFA (2.63 vs. 5.54 mm, P=0.026) and plaque
      rupture sites (P=0.046) were higher in ACS vessels. No relationship was found
      between baseline characteristics and TCFA incidence and plaque rupture. We
      identified ACS (P=0.002), higher mean lipid pool (P=0.002), longer TCFA length
      (P=0.007) and higher number of TCFA (P=0.02) as predictors of plaque rupture
      sites. CONCLUSION: In this in-vivo study, we identified a higher incidence of
      longer TCFAs and plaque rupture sites associated with ACS.

PMID- 21191288
TI  - Mechanisms, prevention, and management of diarrhea in enteral nutrition.
AB  - PURPOSE OF REVIEW: Diarrhea is a common and problematic complication of enteral
      nutrition, about which there has been considerable recent research. This article
      briefly reviews the mechanisms of diarrhea during enteral nutrition and then
      critically appraises the recent and emerging evidence for the prevention and
      management of this distressing complication. RECENT FINDINGS: For many years,
      fiber was extensively investigated for its role in preventing diarrhea; however,
      a more recent focus has been the investigation of specific fiber blends,
      including soluble fibers and prebiotics, for which there is now considerable
      quality evidence. Enteral nutrition may result in deleterious effects on the
      gastrointestinal microbiota, including reductions in bifidobacteria and key
      butyrate producers. Their modulation by prebiotics has been confirmed in studies
      on healthy individuals, but convincing evidence in acutely ill patients is
      required. Probiotics have undergone extensive recent research and their effect on
      preventing diarrhea in enteral nutrition would seemingly be strain dependent.
      Further research is required on systematic approaches to treating diarrhea during
      enteral nutrition. SUMMARY: A number of factors contribute to the pathogenesis of
      diarrhea in enteral nutrition, meaning that approaches to its prevention and
      management are necessarily multifaceted. Approaches to prevent diarrhea during
      enteral nutrition, and a clinical algorithm to manage it, are now presented.

PMID- 21191289
TI  - Somatostatin analogues for treatment of polycystic liver disease.
AB  - PURPOSE OF REVIEW: The present review summarizes the existing knowledge on
      polycystic liver disease (PCLD) and highlights the progress made in medical
      treatment for this condition in the past year. RECENT FINDINGS: PCLD is
      associated with autosomal dominant polycystic kidney disease (ADPKD) and
      autosomal dominant PCLD. Signaling pathways of adenosine 3',5'-cyclic
      monophosphate (cAMP) and mammalian target of rapamycin (mTOR) are aberrantly
      regulated in polycystic livers and promote hepatic cystogenesis. Somatostatin
      analogues reduce intracellular cAMP, and this might prevent fluid accumulation in
      hepatic cysts. Several clinical trials published over the last year now show that
      somatostatin analogues when given for 6-12 months in patients with ADPKD and PCLD
      decrease total liver volume, attenuate polycystic kidney volume, and improve
      perception of health. In two recent studies mTOR inhibitors failed to halt the
      progression of ADPKD. It is still too early to recommend to start somatostatin
      analogues in PCLD and definitive answers should come from future clinical trials.
      SUMMARY: Somatostatin analogues are promising new medical drug options in the
      treatment of PCLD. However, more needs to be elucidated with regard to molecular
      mechanisms in hepatic cystogenesis, the uncertainty who will respond to therapy
      and long-term outcomes.

PMID- 21191290
TI  - Insight into renal Mg2+ transporters.
AB  - PURPOSE OF REVIEW: This review aims to describe the recent findings concerning
      novel Mg transporters as putative interesting players in renal transepithelial Mg
      transport. RECENT FINDINGS: So far, the best characterized Mg transport proteins
      are found in prokaryotes and yeast cells. In recent years, phylogenetic analysis
      and differential gene expression studies have led to the identification of
      numerous genes associated with Mg transport in eukaryotes. In addition to the
      well known transient receptor potential channel melastatin (TRPM), members 6 and
      7, and the mitochondrial transporter Mrs2, additional Mg-transporting protein
      families can be acknowledged including the magnesium (Mag) transporters, the
      solute carrier (SLC) family 41 members, ancient conserved domain proteins (ACDP),
      nonimprinted in Prader-Willi/Angelman syndrome (NIPA) proteins, membrane Mg
      transporters (MMgT) and huntingtin-interacting protein 14 (HIP14). SUMMARY: The
      identification of several mammalian proteins involved in Mg transport highlights
      the physiological importance of this cation and its tight regulation in numerous
      tissues. Further investigation of these transporters might represent a key tool
      to complement our current knowledge about renal Mg handling.

PMID- 21191291
TI  - The identification of phosducin as a novel candidate gene for hypertension and
      its role in sympathetic activation.
AB  - PURPOSE OF REVIEW: The primary objective of this review is to familiarize readers
      with the recent identification of phosducin (Pdc) as a novel candidate gene for
      stress-induced hypertension using comparative genetics and the elucidation of its
      role in sympathetic activation. RECENT FINDINGS: Phosducin was previously
      identified as a G-protein regulator expressed in the retina and pineal gland.
      Knowledge of its physiological role as a G-protein regulator was limited. A
      recent study by Beetz et al. based on comparative genetics of mice and humans
      establishes Pdc as a novel candidate gene for stress-induced hypertension. This
      study further delineates the role of phosducin as a regulator of sympathetic
      activity in postsynaptic ganglia and highlights the importance of sympathetic
      function in blood pressure regulation. In addition, it demonstrates the utility
      of the complementary approaches of population-based association testing and
      animal model genetics in the discovery of genes for complex phenotypes. SUMMARY:
      The identification of Pdc as a gene for stress-induced hypertension offers new
      insights into the relationship between sympathetic nervous system activation,
      blood pressure regulation and genetic factors. It has implications for both the
      treatment of hypertension and kidney disease and may represent a new target for
      novel therapeutics.

PMID- 21191292
TI  - Evaluation and management of glaucoma after keratoprosthesis.
AB  - PURPOSE OF REVIEW: To review the causes and treatment of glaucoma in Boston
      keratoprosthesis (K-pro) recipients. RECENT FINDINGS: Glaucoma exists in up to
      three-quarters of patients who undergo K-pro surgery. After K-pro placement,
      intraocular pressure (IOP) is measured by digital palpation, which has been found
      to be reliable in trained observers. The onset or progression of glaucoma in K
      pro patients should be monitored through visual field testing, direct
      visualization and structural imaging of the optic nerve. Although medical therapy
      is an option, one-half to three-quarters of K-pro recipients are surgically
      managed with a glaucoma drainage device (GDD) or, less commonly,
      cyclophotocoagulation. SUMMARY: Glaucoma is a common and permanent blinding
      sequelae of K-pro surgery. In K-pro patients, elevated IOP and changes in the
      optic nerve head should result in a high index of suspicion for glaucoma.
      Management is frequently surgical and typically entails placement of a GDD.

PMID- 21191293
TI  - Management of retained lens fragments in complicated cataract surgery.
AB  - PURPOSE OF REVIEW: To evaluate and review the current literature on the
      management of retained lens material with pars plana vitrectomy (PPV) and
      lensectomy after complicated cataract surgery. RECENT FINDINGS: Recent studies on
      retained lens fragments in cataract surgery support early referral to a
      vitreoretinal specialist, and indicate that visual outcomes are favorable with
      current vitrectomy and lensectomy techniques. Nearly 83% of patients without
      preexisting eye disease who undergo PPV achieve visual acuity of 20/40, whereas
      5.5% of patients have postoperative acuity of 20/200 or worse. In a multivariate
      analysis, the predictors for 20/40 or better vision were presenting acuity,
      insertion of a posterior chamber lens at the time of cataract surgery, and
      absence of preoperative eye disease. Retinal detachment and secondary glaucoma
      were the major causes of ocular morbidity. Most retrospective studies assessing
      the timing of vitrectomy and lensectomy show no advantage for early (within 1
      week) PPV. Delayed vitrectomy beyond 30 days is associated with poorer outcomes.
      With technological advances, small gauge vitrectomy is considered a viable
      alternative surgical approach to standard vitrectomy with phacofragmentation.
      SUMMARY: Given favorable outcomes reported with planned PPV, the primary
      intraoperative goals of the cataract surgeon encountering posterior displacement
      of lens material are to remove lens material that is accessible from the anterior
      approach, remove vitreous from the anterior segment, and place an anterior or
      preferably posterior chamber intraocular lens. Early involvement of the retinal
      surgeon facilitates the evaluation and timing for vitrectomy and lensectomy based
      on the clinical course.

PMID- 21191294
TI  - Role of endoscopic approach in the management of inverted papilloma.
AB  - PURPOSE OF REVIEW: The aim of this work, based on a recent review of the
      literature concerning sinonasal inverted papilloma, is to describe the diagnostic
      strategy for inverted papilloma and to propose an algorithm for the choice of
      surgical techniques, based on recent results of clinical series. RECENT FINDINGS:
      Traditionally, inverted papilloma was managed through an open approach.
      Endoscopic techniques have been developed, first combined with an open approach,
      and then exclusively endoscopic with the advent of medial maxillectomy and median
      drainage or Draf procedures. Numerous case series strongly support that they now
      represent the treatment modality of choice. SUMMARY: This is a review concerning
      recent findings about inverted papilloma, based on recent literature
      revision.Diagnosis of inverted papilloma has to be made before surgery, and
      planning of the surgical strategy is based on the comparison of computed
      tomography and MRI, with the aim of targeting the insertion of the tumor. With
      the help of expanded surgical procedures, endoscopic surgery has become the gold
      standard for the treatment of the vast majority of inverted papilloma. In case of
      massive frontal or supraorbital extensions, the frontal osteoplastic flap is the
      complementary approach of choice.

PMID- 21191295
TI  - Recalcitrant chronic rhinosinusitis: investigation and management.
AB  - PURPOSE OF REVIEW: We discuss the care of patients failing the typical medical
      and surgical management for chronic rhinosinusitis who need further evaluation to
      rule out various mimics of sinus disease and other disorders that may require
      specific treatment plans. We also look at the many treatment options for the
      recalcitrant sinusitis patient recently published. RECENT FINDINGS: Work-up of
      diseases such as gastroesophageal reflux, dental infection and immunodeficiency
      in the chronic rhinosinusitis patient are discussed. There have been multiple
      treatment options evaluated in the literature in the past year, including long
      term macrolide therapy and various antibiotic, antifungal, and surfactant
      irrigations. Recommendations regarding these therapies are discussed. SUMMARY:
      Patients with recalcitrant chronic rhinosinusitis offer a significant challenge
      to the otolaryngologist. This review provides a structured look at both
      diagnosing and treating the disease processes in these patients, with recently
      published literature presented.

PMID- 21191297
TI  - Changing the topography of acne with topical medications.
AB  - PURPOSE OF REVIEW: Acne vulgaris is a common skin condition that affects
      approximately 40-50 million Americans annually. The peak incidence of acne occurs
      during adolescence and young adulthood, with approximately 80% of persons aged 11
      30 years having at least minor acne. Because the onset of acne is typically in
      early adolescence, pediatricians are often at the front-lines in terms of caring
      for patients with this chief complaint. RECENT FINDINGS: Over the last 2 years,
      new acne therapies have become available. These include new combination fixed
      dose products, which may allow for greater flexibility in treatment and greater
      patient compliance. New topical antibiotics have also come to the market,
      providing more therapeutic options for mild to moderate inflammatory acne.
      Lastly, acne therapies involving the use of light sources and photosensitizers
      are currently being developed, which may provide a whole new modality for
      managing complicated patients. SUMMARY: Successful management of acne requires
      the physician to make a thorough assessment of the patient's acne severity,
      predominant lesion type, skin type, and lifestyle in order to pair each
      individual patient's needs with the appropriate anti-acne therapy. This article
      provides an overview of the pathophysiology of acne and pre-existing topical
      therapies. It then discusses some novel acne therapies and outlines how they
      might fit into a physician's treatment strategy.

PMID- 21191296
TI  - Evaluation and management of critically ill children with acute kidney injury.
AB  - PURPOSE OF REVIEW: This review will highlight recent studies on the diagnosis of
      acute kidney injury (AKI), review the differential diagnosis, highlight the
      importance of cumulative fluid overload and provide key management strategies for
      the pediatric patient with AKI. RECENT FINDINGS: Over the last decade, serum
      creatinine-based categorical definitions of AKI have been accepted, which allow
      detection earlier in the disease process. Evidence-based modifications of these
      definitions have occurred. Fluid overload portends poor outcomes in critically
      ill patients. Significant improvements in our understanding of the
      pathophysiology of glomerular/vascular causes of AKI have occurred. SUMMARY:
      Categorical definitions of AKI have shown that higher AKI portends poor outcomes
      even with adjustment for severity of illness and other confounders. Cumulative
      fluid overload independently predicts poor outcomes. Strategies to prevent and/or
      treat fluid overload are likely to improve outcomes.

PMID- 21191298
TI  - Current understanding of fever and host immunity.
AB  - PURPOSE OF REVIEW: Inherited and acquired immune system dysfunctions associated
      with fever are reviewed. Recent evidence of best practices in the diagnosis and
      treatment of fever caused by infections in children are also discussed. RECENT
      FINDINGS: Descriptive studies on clinical presentation of periodic fever and
      outcomes associated with and without interventions are discussed. Diagnostic
      evaluation and therapy of fever and neutropenia in cancer patients and challenges
      associated with the diagnosis of Kawasaki disease are also included. New evidence
      on the treatment of urinary tract infection in the neonate, and clinical
      evaluation tools for febrile infants, are reviewed. SUMMARY: Immune-dysfunction
      as a cause of fever is not well understood. In order to target therapy
      appropriately, more studies are needed to understand the pathogenesis of fever in
      this population. Better diagnostic methods are available for detection of
      viruses, especially in patients with fever and neutropenia, but further
      investigation is required for the interpretation of those results.

PMID- 21191299
TI  - Recent developments in treatment for simple bone cysts.
AB  - PURPOSE OF REVIEW: The purpose of this paper is to review treatment strategies
      for simple bone cysts (SBCs). RECENT FINDINGS: Recent studies have focused on
      disrupting the wall of the cyst in combination with injectable bone substitutes.
      Bone substitutes are minimally invasive, provide an osteoconductive scaffold, and
      are relatively easy to use. Many of these studies, however, have methodological
      issues (uncontrolled, not randomized, unblinded outcome assessment, or short-term
      follow-up) and inconsistent radiographic outcomes making it difficult to
      determine the benefits of these newer treatment strategies. SUMMARY: Based on a
      single randomized clinical trial, steroids are the only evidence-based treatment
      for SBCs. Further basic science is needed to understand the pathoetiology and to
      develop future biologic solutions. Multimodal treatment strategies with opening
      of the medullary canal and disruption of the cyst wall, filling defect with a
      bone substitute, and possible biologic treatment of the cyst membrane may be the
      best strategy. When considering cysts of the lower extremity, structural support
      may be required in addition to treatment of the cyst.

PMID- 21191300
TI  - A second-generation pneumococcal conjugate vaccine for prevention of pneumococcal
      diseases in children.
AB  - PURPOSE OF REVIEW: A second-generation 13-valent pneumococcal conjugate vaccine
      (PCV13) was licensed and recommended for universal immunization of children
      through age 5 years in 2010. Its introduction is intended to address the residual
      burden of pneumococcal diseases that persists a decade after the introduction of
      PCV7. RECENT FINDINGS: Immunization with PCV7 has resulted in a substantial
      decline in pneumococcal diseases caused by vaccine serotypes in both vaccinated
      and unvaccinated persons in the USA. However, an increase in disease due to
      nonvaccine serotypes, including empyema; the emergence of multidrug, including
      ceftriaxone, resistant serotype 19A strains; and the need for broader serotype
      coverage to address the global disease burden provides a rationale for a second
      generation conjugate vaccine that includes serotypes 1, 3, 5, 6A, 7F and 19A.
      SUMMARY: This article reviews the lessons learned from a decade of experience
      with PCV7, the increasing problem of disease due to nonvaccine serotypes, and the
      likelihood of PCV13 to impact the residual disease burden. We contrast the
      potential differences in prevention of invasive pneumococcal disease compared
      with nonbacteremic pneumonia and acute otitis media. We conclude with the current
      recommendations for PCV13 providing a rationale for immunization through age 5
      years to create both direct and indirect protection in the population.

PMID- 21191301
TI  - Metabolic syndrome and bariatric surgery in stone disease etiology.
AB  - PURPOSE OF REVIEW: To review the prevalence and mechanisms of stone formation in
      patients with metabolic syndrome and in those submitted to bariatric surgery.
      RECENT FINDINGS: MetS is associated with urinary stone disease, which appears to
      be sustained by dietetic factors and insulin resistance. The latter represented
      in obesity and diabetes favors uric acid precipitation in urine via a more acidic
      urinary load. Patients submitted to modern bariatric surgery are at risk of
      nephrolithiasis and nephropathy as a consequence of malabsorption and
      hyperoxaluria, which are more consistent after Roux-en-Y gastric bypass than
      after gastric banding. Other stone risk factors such as hypocitraturia may also
      be present. SUMMARY: Patients with metabolic syndrome and those submitted to
      modern bariatric surgery are both at risk of nephrolithiasis and nephropathy.
      Accurate stone screening careful monitoring of renal function and diet counseling
      are strongly encouraged in these patients.

PMID- 21191302
TI  - Extended lymph node dissection: bladder, kidney.
AB  - PURPOSE OF REVIEW: To present recent advances in the field of lymph node
      dissection (LND) in the context of bladder cancer, upper urinary tract urothelial
      carcinoma and renal cell carcinoma with focus on dissection extent. RECENT
      FINDINGS: A recent Technetium-based lymph node mapping study has provided several
      observations to help guide the scientific practice of LND during radical
      cystectomy. Only 8-10% of primary lymphatic landing sites were located above the
      uretero-iliac crossing. In contrast, considerable lymph nodes were found in the
      fossa of Marcille and the internal iliac region. Intraoperative frozen sections
      are unlikely to abbreviate the LND procedure. Total nodal yield is influenced by
      numerous factors and may not represent the ideal surrogate for adequacy of LND.
      The lymphatic drainage of the upper urinary tract is less predictive. For upper
      urinary tract urothelial cancer, conflicting data question even the staging
      benefit. In contrast, the results from the sole prospective randomized trial
      evaluating the value of LND in renal cell carcinoma cannot be generalized because
      of the limited inclusion of patients with higher stage disease. SUMMARY: In
      invasive bladder cancer, meticulous extended LND offers both a prognostic and
      therapeutic benefit. However, the proximal boundaries of the LND template remain
      undefined. For upper urinary tract urothelial cancer there is a need to define a
      standardized approach (indication, template) in view of directing patients
      properly to adjuvant therapies and consecutively evaluate both prognostic and
      therapeutic value of LND. Similarly, the need for standardization accounts for
      renal cell carcinoma.

PMID- 21191303
TI  - Advantages of doxapram for post-anaesthesia recovery and outcomes in bariatric
      surgery patients with obstructive sleep apnoea.

PMID- 21191304
TI  - Factors associated with and consequences of unplanned post-operative intubation
      in elderly vascular and general surgery patients.
AB  - OBJECTIVE: Unplanned post-operative intubation (UPI) may be associated with
      significant morbidity and/or mortality after surgery. The purpose of this
      investigation was to determine the incidence and predictors of UPI in elderly
      patients who underwent general and vascular surgical procedures. METHODS: Data
      from the American College of Surgeons National Surgical Quality Improvement
      Program Participant Use Data File was used to calculate the incidence of UPI in
      all elderly vascular and general surgery patients undergoing operations from 2005
      to 2008. UPI was defined as a requirement for the placement of an endotracheal
      tube and mechanical or assisted ventilation because of the onset of respiratory
      or cardiac failure manifested by severe respiratory distress, hypoxia,
      hypercarbia or respiratory acidosis within 30 days of the index operation.
      Univariate factors associated with UPI were identified. Multivariate stepwise
      logistic regression was used to calculate odds ratios (ORs) for UPI after
      controlling for known clinically relevant cofactors. MAIN OUTCOME MEASURES:
      Incidence of UPI as well as morbidity and mortality associated with UPI. RESULTS:
      Among 115 692 patients, 3.3% required UPI. Univariate predictors of UPI were
      older age group, chronic obstructive pulmonary disease, low pre-operative
      functional status as well as emergency operation. UPI was associated with an 18
      fold increased risk of death as well as significantly increased hospital length
      of stay. Multivariate analysis identified several predictors of UPI with re
      operation having the greatest odds for UPI (OR = 4.5; 95% confidence interval =
      4.29-4.86, P < 0.001). CONCLUSION: Although the incidence of UPI in this elderly
      surgical cohort was low, it was associated with significant morbidity and
      mortality as well as prolonged hospital length of stay, underscoring the need for
      accurately identifying modifiable risk factors.

PMID- 21191305
TI  - Association of CYP1B1 gene polymorphisms with susceptibility to endometrial
      cancer: a meta-analysis.
AB  - The objective of this meta-analysis was to quantitatively summarize the
      association of CYP1B1 gene polymorphisms and endometrial cancer risk. Data were
      collected from the following electronic databases: PubMed,Elsevier Science
      Direct, Chinese Biomedical Literature Database, Chinese National Knowledge
      Infrastructure and Wanfang, with the last report up to June 2010. Meta-analysis
      was conducted in a fixed/random effect model. Out of the 715 papers retrieved 12
      studies (3605 cases and 5692 controls) on the association of CYP1B1 gene
      polymorphisms with endometrial cancer risk in different ethnic groups were
      identified. Meta-analysis was performed for CYP1B1 gene polymorphisms: R48G (C/G,
      five studies), L432V (C/G, 12 studies), N453S (A/G, four studies), and A119S
      (G/T, five studies). We did not detect any association of CYP1B1 gene A119S
      polymorphism with endometrial cancer. An association of CYP1B1 gene R48G
      polymorphism with endometrial cancer was found [GG vs. GC+CC: odds ratio
      (OR)=0.55, 95% confidence interval (CI): 0.42-0.73, P<0.0001; GG vs. CC: OR=0.46,
      95% CI: 0.23-0.91, P=0.03]. We found that CYP1B1 gene L432V polymorphism was
      associated with a significantly increased risk of endometrial cancer (G vs. C:
      OR=1.23, 95% CI: 1.06-1.43, P=0.007; GC+GG vs. CC:OR=1.24, 95% CI: 1.08-1.43,
      P=0.003; GC vs. CC: OR=1.16, 95% CI: 1.04-1.29, P=0.009). Moreover, we detected
      the association of CYP1B1 gene N453S polymorphism with endometrial cancer (G vs.
      A: OR=0.82,95% CI: 0.72-0.94, P=0.005; GA vs. AA: OR=0.81, 95% CI: 0.69-0.95,
      P=0.01). In conclusion, this meta-analysis provides strong evidence that CYP1B1
      gene R48G, L432V, and N453S polymorphisms are associated with endometrial cancer
      risk, but not A119S.

PMID- 21191306
TI  - Effects of active and passive smoking on Crohn's disease and ulcerative colitis
      in a cohort from a regional hospital.
AB  - OBJECTIVE: Smoking is detrimental for Crohn's disease (CD), but beneficial for
      ulcerative colitis (UC). Earlier, we studied the effects of active and passive
      smoking in CD and UC patients from a university hospital. This study was
      conducted to assess the same effects in patients from a regional hospital.
      METHODS: A questionnaire focusing on cigarette smoke exposure was sent to 382
      patients. Returned questionnaires (84%: 128 CD and 192 UC patients) were
      incorporated into a retrospective chart review about disease behaviour and
      received therapy. RESULTS: At diagnosis there were 52% (95% confidence interval:
      43-60%) smokers among CD patients, 40% in a control population and 25% (95%
      confidence interval: 18-31%) among UC patients. There were less former (19 vs.
      31%, P = 0.013) and never smokers at diagnosis (30 vs. 44%, P = 0.009) in CD than
      in UC. No detrimental effects of active or passive smoking on the course of CD
      were observed. UC patients who continued smoking after diagnosis needed less
      often two or more hospitalizations than never smokers (5 vs. 25%, P = 0.036).
      Otherwise no clear beneficial effects of active smoking on UC were observed.
      Passively smoking UC patients experienced more often extraintestinal
      manifestations (25 vs. 7%, P = 0.029) than nonpassive smokers. CONCLUSION: Also
      in a regional hospital inflammatory bowel disease population smoking is a risk
      factor to develop CD and protects against developing UC. We found no detrimental
      effects of smoking on the disease course of CD and no clear beneficial effects on
      the course of UC.

PMID- 21191307
TI  - Heme oxygenase-1 polymorphism is not associated with risk of colorectal cancer: a
      Danish prospective study.
AB  - OBJECTIVE: Intake of red and processed meat confers risk of colorectal cancer
      (CRC). We wanted to test whether heme in meat promotes carcinogenesis. METHODS:
      Heme oxygenase-1 (HO-1, HMOX1) A-413T (rs2071746) was assessed in a nested case
      cohort study of 383 CRC cases and 763 randomly selected participants from a
      prospective study of 57 053 individuals. Incidence rate ratios and 95% confidence
      intervals were calculated. RESULTS: No association was found between the HO-1
      polymorphism and CRC (P value for trend for the fully adjusted estimates = 0.29).
      No interaction with meat intake was found (P value for interaction = 0.55).
      CONCLUSION: The studied HO-1 polymorphism was not associated with risk of CRC
      suggesting that heme from meat is not important in CRC development.

PMID- 21191308
TI  - A meta-analysis of sexual dysfunction in psychiatric patients taking
      antipsychotics.
AB  - The aim of this meta-analysis was to quantify sexual dysfunction (SD) in patients
      treated with antipsychotics on the basis of selected papers that specifically
      investigated this type of adverse events by means of adequate instruments. A
      literature research was conducted using three electronic databases. Studies
      providing measures of SD in patients taking antipsychotics and providing separate
      data on single drugs were considered for inclusion. Our primary outcome measure
      was the rate of total SD, and our secondary outcome measures were the rates of
      desire, arousal, and orgasm dysfunction. We found that significant differences
      exist across different antipsychotics in terms of total SD, such that, partially
      consistent with the traditional dichotomy between prolactin-raising and prolactin
      sparing antipsychotics, quetiapine, ziprasidone, perphenazine, and aripiprazole
      were associated with relatively low SD rates (16-27%), whereas olanzapine,
      risperidone, haloperidol, clozapine, and thioridazine were associated with higher
      SD rates (40-60%). Apart from a few exceptions, secondary analyses substantially
      confirmed the primary outcome measure. However, sensitivity analyses showed a
      significant impact of several variables on SD rates. In addition, taking into
      account several limitations, including the difficulty to disentangle SD related
      to drugs from SD related to illness itself, further studies are needed to
      determine more thorough evidence concerning antipsychotic-induced SD.

PMID- 21191309
TI  - Association between medication possession ratio, virologic failure and drug
      resistance in HIV-1-infected adults on antiretroviral therapy in Cote d'Ivoire.
AB  - BACKGROUND: Adherence is a strong determinant of viral suppression with
      antiretroviral therapy (ART) but measuring it is challenging. Medication delivery
      can be measured accurately in settings with computerized prescription databases.
      We studied the association between medication possession ratio (MPR), virologic
      suppression, and resistance to ART in Cote d'Ivoire. METHODS: We conducted a
      prospective cohort study of HIV-1-infected adults initiating ART in 3 clinics
      using computerized monitoring systems. Patients had viral load (VL) tests at
      month 6 (M6) and month 12 (M12) after ART initiation and genotype tests if VL was
      detectable (>=300 copies/mL). MPR was defined as the number of daily doses of
      antiretroviral drug actually provided divided by the total number of follow-up
      days since ART initiation. RESULTS: Overall, 1573 patients started ART with
      stavudine/zidovudine plus lamivudine plus nevirapine/efavirenz. At M6 and M12,
      996 and 942 patients were in active follow-up; 20% (M6) and 25% (M12) of patients
      had detectable VL, including 7% (M6) and 11% (M12) with >=1 resistance mutation.
      Among patients with MPR of >=95%, 80%-94%, 65%-79%, 50%-64%, and <50% at M12, the
      proportion with detectable VL [resistance] was 9% [4%], 17% [7%], 45% [24%], 67%
      [31%], and 85% [37%]. Among patients with >=1 mutation at M12, 86% were resistant
      to lamivudine/emtricitabine and/or nevirapine/efavirenz but not to other drugs.
      CONCLUSIONS: MPR was strongly associated with virologic outcomes. Half of those
      with detectable VL at M12 had no resistance mutations. MPR should be used at M6
      to identify patients who might benefit from early interventions to reinforce
      adherence.

PMID- 21191310
TI  - Impaired expression of duodenal iron transporters in Dahl salt-sensitive heart
      failure rats.
AB  - OBJECTIVE: Anemia is common in patients with heart failure and several factors
      have been thought to cause anemia in heart failure. Despite vigorous studies, the
      mechanism underlying the pathophysiology of anemia in heart failure is unknown.
      We investigated the iron regulating system in Dahl salt-sensitive heart failure
      rats to elucidate the mechanism of anemia in heart failure. METHODS: Dahl salt
      sensitive rats were provided either a normal or high-salt diet to initiate heart
      failure progression. A further subset of Dahl salt-sensitive rats underwent an
      iron-deficient diet to induce iron deficiency anemia (IDA). RESULTS: Dahl salt
      sensitive rats, which develop diastolic heart failure, gradually showed
      hypertension and anemia after 8 weeks of high-salt diet. Although serum iron
      levels were decreased, erythropoietin levels were increased in the IDA and heart
      failure groups. Hepatic expression of hepcidin, a central regulator of iron
      metabolism, was downregulated in both IDA and heart failure groups. Duodenal
      cytochrome b (Dcyt-b), divalent metal transporter 1 (DMT-1), and ferroportin are
      the crucial regulators of intestinal iron transport and absorption. Duodenal
      expression levels of these molecules were markedly upregulated in the IDA group,
      but not in the heart failure group. Moreover, intestinal expression of hypoxia
      inducible factor-2alpha, a critical regulator of the transcription of Dcyt-b and
      DMT-1, was upregulated in the IDA group, but not in the heart failure group.
      CONCLUSION: Duodenal iron transporters expression was impaired in Dahl heart
      failure rats. Our data suggest that impaired duodenal iron absorption may occur
      in Dahl heart failure rats. Understanding the mechanism of abnormal iron
      regulating system may lead to new therapeutic strategies in anemia with heart
      failure.

PMID- 21191311
TI  - Blood 25-hydroxyvitamin D concentration and hypertension: a meta-analysis.
AB  - OBJECTIVES: Increasing evidence indicates that vitamin D may influence the risk
      of hypertension, which is a major risk factor for cardiovascular disease. We
      conducted a meta-analysis to quantitatively review and summarize the results on
      the association between blood 25-hydroxyvitamin D concentrations and
      hypertension. METHODS: Relevant studies were identified by a search of PubMed and
      EMBASE databases until November 2010. We also reviewed the references of
      retrieved articles. We included prospective and cross-sectional studies with
      blood 25-hydroxyvitamin D concentrations as the exposure and hypertension as the
      outcome. Studies had to report results as a relative risk or an odds ratio. We
      used random-effects model. RESULTS: Of the 18 studies included in the meta
      analysis, 4 were prospective studies and 14 were cross-sectional studies. The
      pooled odds ratio of hypertension was 0.73 [95% confidence interval (CI) 0.63
      0.84] for the highest versus the lowest category of blood 25-hydroxyvitamin D
      concentration. In a dose-response meta-analysis, the odds ratio for a 40 nmol/l
      (16 ng/ml) (approximately 2 SDs) increment in blood 25-hydroxyvitamin D
      concentration was 0.84 (95% CI 0.78-0.90). CONCLUSION: Findings from this meta
      analysis indicate that blood 25-hydroxyvitamin D concentration is inversely
      associated with hypertension.

PMID- 21191312
TI  - CA125 screening after risk-reducing salpingo-oophorectomy: are the titers too
      high, or is it all just too much?

PMID- 21191313
TI  - Efficiency analysis of using tailored individual doses of radioiodine and fine
      tuning using a low-dose antithyroid drug in the treatment of Graves' disease.
AB  - PURPOSE: To evaluate the effect of using tailored individual doses of radioiodine
      (131I) and fine tuning using low-dose antithyroid drug (ATD) in the treatment of
      Graves' disease, and an attempt to establish a therapeutic strategy that can keep
      both high rate of euthyroidism and low incidence of hypothyroidism. METHODS: The
      dose of radioiodine was calculated using the calculated dose formula, and low
      dose ATD was used as a way of fine tuning during follow-up. The intended dose of
      radioiodine was modified according to the patient's age at radioiodine therapy,
      thyroid size, and duration of hyperthyroidism before radioiodine therapy in the
      study group; it was set as 2.96 MBq/g of thyroid in the control group. Twenty
      patients with Graves' disease were nonrandomly assigned to the control group and
      98 patients with Graves' disease to the study group. The outcomes, which included
      euthyroidism, hypothyroidism, and persistent hyperthyroidism, were determined
      according to the patients' states at the end of follow-up. RESULTS: In the study
      group, 74 patients (75.5%) achieved the euthyroid state, six patients (6.1%)
      became hypothyroid, and 18 patients (18.4%) remained hyperthyroid. The rate of
      euthyroidism was statistically different between the study group and the control
      group (75.5 vs. 50%, P=0.03). Of 98 patients with Graves' disease in the study
      group, 19 patients were additionally treated with ATD during follow-up, and 12
      patients achieved euthyroidism. In different age groups or duration of
      hyperthyroidism groups, the rate of euthyroidism was not statistically different
      among subgroups of goiter grade 1, grade 2, and grade 3 (P>0.05). Similarly, in
      different age groups or duration of hyperthyroidism groups, the incidence of
      hypothyroidism was not statistically different among subgroups of goiter grade 1,
      grade 2, and grade 3 (P>0.05). However, binary logistic regression analysis
      showed that thyroid size was associated with overtreatment and undertreatment in
      our study. CONCLUSION: Individual doses of radioiodine, adjusted according to the
      patient's age, thyroid size, and duration of hyperthyroidism, combined with low
      dose ATD for some patients, 1 month or more after radioiodine therapy, was an
      effective method for treating Graves' disease. Our data showed that using
      tailored individual doses of radioiodine and fine tuning using low-dose ATD may
      well be a way to keep both high rate of euthyroidism and low incidence of
      hypothyroidism. The dose of radioiodine should be decreased a little for small
      goiter and increased a little for large goiter on the basis of our treatment
      protocol in future study.

PMID- 21191314
TI  - Serum thyroglobulin predicts thyroid remnant ablation failure with 30 mCi iodine
      131 treatment in patients with papillary thyroid carcinoma.
AB  - BACKGROUND: Most patients with differentiated thyroid cancer are treated with
      radioiodine (131-I) after thyroidectomy. The characteristics predictive of
      successful remnant ablation with low activities of 131-I are ill defined and
      could help stratify patients into those who should receive higher activities.
      METHODS: In a case series of 193 consecutive patients with papillary thyroid
      cancer who underwent total thyroidectomy and received 30 mCi (1110 MBq) of 131-I,
      we assessed the percentage of successful radioremnant ablation as defined by a
      composite of scintigraphic and biochemical endpoints. Clinical, histological,
      scintigraphic, and biochemical covariables were analyzed to identify associations
      with treatment failure. RESULTS: Successful radioremnant ablation with low
      activity 131-I was obtained in 78% of the entire cohort of patients. The presence
      of limited microscopic extrathyroidal extension, nodal micrometastases, or an
      elevated stimulated ablation was associated with failure to ablate the remnant.
      While accounting for other factors in a multivariable analysis, patients with an
      ablation thyroglobulin of at least 6 MUg/l were at a more than five times greater
      risk (P<0.001) to fail 30 mCi 131-I remnant ablation. CONCLUSION: The majority of
      patients with papillary thyroid carcinoma experienced successful ablation.
      However, elevated-stimulated ablation thyroglobulin levels were strongly
      predictive of ablation failure, suggesting that this biochemical marker
      correlates with a more aggressive tumor profile and identifies those patients who
      might benefit from additional therapy.

PMID- 21191316
TI  - Ribavirin plasma concentration measurements in patients with hepatitis C: early
      ribavirin concentrations predict steady-state concentrations.
AB  - BACKGROUND: Ribavirin is an essential component in the treatment of chronic
      hepatitis C (HCV) infection. Although ribavirin dose is weight-based, data in the
      literature suggest large between-patient variability in plasma ribavirin
      concentrations. Recent studies indicate that higher ribavirin exposure results in
      higher sustained viral response rates. Monitoring ribavirin concentration is
      suggested in the literature, but it is unclear at what time point during
      treatment plasma ribavirin concentrations should be monitored. AIM: To
      investigate the association between early plasma ribavirin concentrations and
      ribavirin dosing with steady-state (Css) concentration and the between- and
      within-patient variability in plasma ribavirin concentration in clinical
      practice. METHODS: We performed a prospective observational cohort study in
      patients with HCV who received pegylated interferon in combination with oral
      weight-based ribavirin (12-15 mg/kg) twice daily. Trough plasma ribavirin
      concentrations at Weeks 1, 2, 4, 8, 12, 16, 20, and 24 were studied using a
      validated high-performance liquid chromatography assay. RESULTS: In total, 53
      patients (37 male, 16 female) with a mean age of 51 years (range, 26-68 years)
      were included and 209 samples were collected. There was a significant correlation
      between Week 2 as well as Week 4 and plasma ribavirin Css (r = 0.589 and r =
      0.714, P < 0.05, respectively). Ribavirin Css was reached at Week 8 of HCV
      treatment. There was no correlation between dose in mg/kg and Css (r = 0.181, P =
      0.263). The between- and within-patient coefficients of variation of plasma
      ribavirin concentrations at Week 8 and beyond were 43% and 13%, respectively.
      CONCLUSION: In HCV-infected patients, ribavirin steady-state concentrations can
      be predicted by measurement of concentrations made early after the start of
      therapy.

PMID- 21191317
TI  - Benzodiazepines and sedative-hypnotics in blood of drivers under the influence
      and their association with other common illegal drug use and national sales
      figures.
AB  - The authors examined benzodiazepine and sedative-hypnotic positive cases of
      drivers under the influence (DUI) in Finland from 1997 to 2008. Factors studied
      were the number of cases positive for the most commonly encountered of these
      pharmaceuticals, simultaneous use of amphetamine and/or cannabis, and the
      relationship between the number of DUI cases and overall sales in Finland for the
      individual pharmaceuticals. Data for 20037 cases positive for the relevant drugs
      were retrieved from the laboratory database of the Alcohol and Drug Analytics
      Unit, National Institute for Health and Welfare. Toxicological results were from
      blood analysis. Drug sales figures for each pharmaceutical were obtained from the
      Finnish Medicines Agency. An increase in DUI cases that were positive for the
      drugs studied was evident, which reflected the overall increase in positive DUI
      cases detected annually. The proportion of relevant cases was typically 75% or
      higher of all positive DUI cases up to 2003, the year that the Finnish zero
      tolerance law was introduced, and then decreased to 66.2% in 2008. Diazepam was
      consistently the most commonly detected nonmetabolite drug. The prevalence of
      clonazepam and alprazolam increased sharply from 2004 onward. Metabolites of
      diazepam, nordiazepam, temazepam, and oxazepam, were other common findings.
      Associated use of amphetamine and/or cannabis was also common in these DUI cases,
      typically between 56% and 66% of cases. An increase in the number of DUI cases
      showing combined use of benzodiazepines and sedative-hypnotics with amphetamines
      in particular was apparent after zero tolerance legislation and the introduction
      in 2005 of an effective on-site screening device for the stimulant. Ratios of DUI
      cases to sales figures showed an increase in detection of clonazepam-positive DUI
      cases from 2003. Diazepam, midazolam, and alprazolam also exhibited relatively
      high ratios, which increased from 1997 to 2008.

PMID- 21191315
TI  - Genetic association of bipolar disorder with the beta(3) nicotinic receptor
      subunit gene.
AB  - OBJECTIVE: Owing to the clinical relationship between bipolar disorder and
      nicotine dependence, we investigated two research questions: (i) are genetic
      associations with nicotine dependence different in individuals with bipolar
      disorder as compared with individuals without bipolar disorder, and (ii) do loci
      earlier associated with nicotine dependence have pleiotropic effects on these two
      diseases. METHOD: Our study consisted of 916 cases with bipolar disorder and 1028
      controls. On the basis of known associations with nicotine dependence, we
      genotyped eight single-nucleotide polymorphisms (SNPs) on chromosome 8 (three
      bins) in the regions of CHRNB3 and CHRNA6, and six SNPs on chromosome 15 (three
      bins) in the regions of CHRNA5 and CHRNA3. RESULTS: To determine whether the
      genetic associations with nicotine dependence are different in bipolar disorder
      than in the general population, we compared allele frequencies of candidate SNPs
      between individuals with nicotine dependence only and individuals with both
      nicotine dependence and bipolar disorder. There were no statistical differences
      between these frequencies, indicating that genetic association with nicotine
      dependence is similar in individuals with bipolar disorder as in the general
      population. In the investigation of pleiotropic effects of these SNPs on bipolar
      disorder, two highly correlated synonymous SNPs in CHRNB3, rs4952 and rs4953,
      were significantly associated with bipolar disorder (odds ratio 1.7, 95%
      confidence interval: 1.2-2.4, P=0.001). This association remained significant
      both after adjusting for a smoking covariate and analyzing the association in
      nonsmokers only. CONCLUSION: Our results suggest that (i) bipolar disorder does
      not modify the association between nicotine dependence and nicotinic receptor
      subunit genes, and (ii) variants in CHRNB3/CHRNA6 are independently associated
      with bipolar disorder.

PMID- 21191318
TI  - Magnetically recoverable magnetite/gold catalyst stabilized by poly(N-vinyl-2
      pyrrolidone) for aerobic oxidation of alcohols.
AB  - Fe(3)O(4):PVP/Au nanocomposite synthesized via a two-step procedure was tested as
      a quasi-homogenous alcohol oxidation catalyst. It was found that the
      nanocomposite was able to carry out aerobic oxidation of alcohols in water at
      room temperature. Studies show rapid magnetic recoverability and reusability
      characteristics.

PMID- 21191319
TI  - The relationship between phenolics and flavonoids production with total non
      structural carbohydrate and photosynthetic rate in Labisia pumila Benth. under
      high CO2 and nitrogen fertilization.
AB  - A factorial split plot 4 * 3 experiment was designed to examine and characterize
      the relationship among production of secondary metabolites (total phenolics, TP;
      total flavonoids, TF), carbohydrate content and photosynthesis of three varieties
      of the Malaysian medicinal herb Labisia pumila Benth. namely the varieties alata,
      pumila and lanceolata under CO(2) enrichment (1,200 umol mol(-1)) combined with
      four levels of nitrogen fertilization (0, 90, 180 and 270 kg N ha(-1)). No
      varietal differences were observed, however, as the levels of nitrogen increased
      from 0 to 270 kg N ha(-1), the production of TP and TF decreased in the order
      leaves>roots>stems. The production of TP and TF was related to increased total
      non structural carbohydrate (TNC), where the increase in starch content was
      larger than that in sugar concentration. Nevertheless, the regression analysis
      exhibited a higher influence of soluble sugar concentration (r(2) = 0.88) than
      starch on TP and TF biosynthesis. Photosynthesis, on the other hand, displayed a
      significant negative relationship with TP and TF production (r(2) = -0.87). A
      decrease in photosynthetic rate with increasing secondary metabolites might be
      due to an increase in the shikimic acid pathway that results in enhanced
      production of TP and TF. Chlorophyll content exhibited very significant negative
      relationships with total soluble sugar, starch and total non structural
      carbohydrate.

PMID- 21191320
TI  - Design and synthesis of anti-MRSA benzimidazolylbenzene-sulfonamides. QSAR
      studies for prediction of antibacterial activity.
AB  - A series of benzimidazolylbenzenesulfonamide compounds containing electron
      releasing and electron-withdrawing substituents were synthesized and tested for
      their in vitro antibacterial activity. Two BZS compounds showed strong
      antibacterial activity against methicillin-resistant Staphylococcus aureus and
      Bacillus subtilis. Quantitative studies of their structure-activity relationship
      using a simple linear regression analysis were applied to explore the correlation
      between the biological activity and the charges on acidic hydrogen atoms in the
      synthesized compounds.

PMID- 21191328
TI  - [Implants integration into bone tissue: theoretical aspects of the problem].
AB  - It was analyzed the status of dental implants integration into bone tissue
      problem. The concept of stages and mechanisms of development of integration
      process in the implant-bone interface based on literature data and own study was
      presented.

PMID- 21191329
TI  - [Effect of intrauterine hypoxia upon newborn albino rat tooth germ cells anabolic
      activity].
AB  - The aim of this study was to examine the intrauterine hypoxia influence on dental
      hard tissue development. Pregnant rats were exposed in hypoxic environments
      between day 14 and 19 of pregnancy. The study was performed on 36 newborn albino
      rats. Analysis of nucleolar organizator parameters were performed in
      enameloblasts, odontoblasts and saliva gland epitheliocytes. Data obtained
      demonstrated that intrauterine hypoxia decreased nucleolar organizator quantity
      in enameloblasts of tooth germ.

PMID- 21191330
TI  - [Submandibular lymph nodes of rats with arterial hypertension after mandible bone
      damage].
AB  - The structure of submandibular lymph nodes (LN) from rats with arterial
      hypertension (AH) and normal pressure after mandible damage was investigated by
      methods of light microscopy. It was revealed that in submandibular LN of both
      compared groups of animals after induction of inflammatory reaction cortical
      field was extended, bulk density of lymphoid nodules without reproductive centres
      was increased, in nodules with centres mantle was extended and germinative
      centres were decreased. In all structures of LN the numbers of mitosis, imrnuno -
      and plasmoblasts were increased, the contents of reticular cells and macrophages
      were increased only to 4-5 week. In structure of LN from rats with normal
      arterial pressure and with AH the volume of sinus system statistically
      significantly differed: animals with AH had more volume of sinuses on all points
      of observation. Inflammation in the conditions of AH the distinction in cellular
      content of various zones of LN were connected with occurrence or higher number of
      erythrocytes.

PMID- 21191331
TI  - [Some cytokines and cytokines autoantibodies content in the blood serum, oral and
      gingival fluid in odontogenic maxillofacial abscesses].
AB  - Cytokines level and cytokines antibodies in the blood serum, oral and gingival
      fluids was studied in 15 patients with odontogenic maxillofacial abscesses.
      Increased level of the inflammatory cytokines (IL1beta, IL6, IL8) and decreased
      level of the anti-inflammatory cytokines (IL4, IL10) in oral and dentigingival
      fluids. Besides, increased content of autoantibodies of class sIgA to IL8 and
      decreased content of autoantibodies of class sIgA to IL10 was noted.

PMID- 21191332
TI  - [Efficacy determination of Splat Oral Care Foam 2 in 1].
AB  - The new oral hygienic foam Splat Oral Care Foam 2 in 1 was clinically tested.
      Oral hygiene improvement by regular using of oral foam was defined. Saliva pH
      normalization by using of oral foam after meal was detected. Oral Care Foam 2 in
      1 improves efficiency of gingivitis treatment and reduces terms of adaptation to
      fixed and removable dentures.

PMID- 21191333
TI  - [Superelastic constructions in surgical treatment of mandible condylar process
      fractures with full medial head of mandible dislocation].
AB  - Between 2007 and 2009 15 patients with medially dislocated head fractures of
      condylar process were surgically treated in Sechenov Moscow Medical Academy. All
      patients were surgically treated with open reduction--mandibular rami osteotomy,
      replantation of condylar head and osteosynthesis with nikelide titanium gages.
      Modern surgical technologies implementing nikelide titanium gages for
      osteosynthesis simplifies operation technique, decreased surgical trauma and
      increased overall treatment quality of such patients.

PMID- 21191334
TI  - [Study of virus content of Herpes viridae family in parotid secretion of patients
      with inflammatory-dystrophic diseases of salivary glands].
AB  - The study is devoted to disclose the interrelation between Herpes viridae family
      carriage and inflammatory-dystrophic diseases of salivary glands (SG). It was
      shown that inflammatory and dystrophic diseases of SG in observed patients run on
      the background of latent and active chronic herpes-virus infection. In the case
      the frequency of disclosure and content of antibodies to nuclear protein of
      Epstein-Barr virus in the peripheral blood serum in patients with different
      inflammatory and dystrophic SG diseases were statistically significantly higher
      and antibodies to simple 1st type virus and cytomegalovirus lower than in
      patients with different types of maxillofacial region pathology without SG
      involvement. The immediate contamination of parotid secretion by virus of Herpes
      viridae family was detected with the help of polymerase chain reaction in 18% of
      patients with SG diseases.

PMID- 21191335
TI  - [Study of stomatological status in patients of dental implantological clinic
      according to the data of orthopantomography and computer tomography].
AB  - During examination before dental implantation with the use of orthopantomography
      (OPTG) and computer tomography (CT) stomatological status was studied in 242
      patients of the Clinical stomatologic centre of FMBA, Russia. Indices of
      frequency and intensity of dental caries and periodontal disease were determined,
      as well as frequency of maxillary sinuses pathology, evaluation of the
      preliminary endodontic treatment quality was given, morphometric data governing
      frequency of indications to bone-plastic operations were presented. The
      advantages of CT over OPTG were shown during patients examination before dental
      implantations were maid.

PMID- 21191336
TI  - [Problem of the success evaluation criterions of reconstructive operations on the
      example of patients with total auricle defects].
AB  - The difference between prime data and result received after the operation in case
      of patient's photographing in standard angle shorts could be interpreted in
      different ways. Knowledge of the patients' attitude to treatment peculiarities,
      their psychological status gave the surgeon possibility to carry out more
      differentiated and psychologically backed up preparation for treatment in which
      considerable rope played before and after operation rehabilitation. Taking this
      into account it was necessary to note the importance of collaboration of surgeons
      with clinical psychologists which could render help in choosing and developing
      new more informative evaluation techniques.

PMID- 21191337
TI  - [Peculiarities of face regional hemodynamics in treatment of acute purulent jaw
      odontogenic periostitis].
AB  - 53 patients were under observation with acute purulent jaw odontogenic
      periostitis. In 27 out of them after operation as drainage material strips of
      napkin were used, containing as the active components metronidazol, dimexide and
      sodium alginate. Curative process efficacy evaluation was done according to the
      data of hemodynamic study (determination of the artery's diameter, maximal
      systolic speed and index of circulatory resistance) of the magistral face
      arteries. It was established that in the group of patients with rational
      treatment blood circulation in face arterial vessels was restored most actively
      than in the control group with the use of traditional treatment scheme.

PMID- 21191338
TI  - [Comprehensive microbiological and molecular-biological control of using laser
      technologies in ambulatory surgical practice].
AB  - Results of comparative use of different type lasers for surgical treatment of
      patients with medium severity level of periodontitis were presented: group 1-
      erbium laser "Waterlaser Millennium" (41 people); group 2--diode laser "LS-0,97 -
      IRE-Polyus" (25 people); group 3--carbon dioxide laser "SO2-laser LST - 20/01
      Lantset" (21 people). Patients of the comparative group undergone a traditional
      surgical curettage (30 people). A PCR-diagnostic was made to all patients that
      were sent to ambulatory surgical treatment. It revealed carriage of 1 to 4 types
      of periodontium pathogenic bacteria that present ed threat from the point of view
      of infectious complications development in the postoperative period. After using
      laser technologies an increase of periodontium pathogenic species eradication
      frequency was registered (A. actinomycetemcomitans, T. forsithia, P. gingivalis,
      P. intermedia, T. denticola): up to 60, 58 and 60%--for erbium, diode and carbon
      dioxide correspondingly.

PMID- 21191339
TI  - [Maxillary sinus inflammation after operation of dental implantation and sinus
      lifting].
AB  - 16 patients with sinusitis were examined after dental implantation and sinus
      lifting. Possible complication reasons after alveolar process operations were
      disclosed. For dental implantation efficacy elevation in patients with alveolar
      process atrophy the consultation of otolaryngologist was necessary in order to
      disclose hidden pathology on the nasal cavity and sinuses side and also maxillary
      tomography with inclusion of osteo-meatal complex. Operative treatment of
      patients with sinusitis after sinus lifting was necessary in case of free lying
      osteo-plastic material in the sinus, presence of oro-anthral fistula and
      conservative treatment failure.

PMID- 21191340
TI  - [Microcirculation status in supporting tissues in cases of prosthetic treatment
      of mandible in patients with full secondary adentia with the use of implants].
AB  - By the method of laser Doppler fluometry microcirculation in gingival tissues was
      studied in the region of bearing implants in cases of making prosthetics for
      patients with full secondary adentia. It was established that after functional
      loading of the bearing implants in microcirculatory bed of gingival tissues
      hyperemia was developed that was cut short in 3 months that testified to
      normalization of tissue blood flow.

PMID- 21191341
TI  - [Bulla ethmoidalis uncinata: theoretical and practical implications].
AB  - The authors describe the previously unknown morphological structure, bulla
      ethmoidalis uncinata, located at the medial plate of ethmoidal labyrinth that
      forms the upper part of the lateral wall of the nasal cavity in the region of
      middle nasal meatus. It was shown that the absence of semilunar hiatus in the
      nasal cavity may be responsible for fronto-nasal communication through the
      infundibular opening or the crooked fronto-nasal duct. The discovery of bulla
      ethmoidalis uncinata substantially extends our knowledge of the structure of
      human nasal cavity.

PMID- 21191342
TI  - [Clinical and morphological aspects of diagnostics and treatment of exudative
      frontitis].
AB  - The present work is based on the examination of 37 sagittal sawcut sections
      through the heads of human corpses of either gender. Evacuation paths for the
      contents of frontal sinuses were studied experimentally in different types of
      fronto-nasal communication. Two variants of infundibular fronto-nasal
      communication are described, lateral and medial, formed by the bony septum
      between uncinate process and bulla ethmoidalis uncinata. It was shown that the
      direction of evacuation of the contents of a frontal sinusis and the possibility
      of their rhinoscopic identification are directly dependent on the type of the
      naso-frontal communication. Cannulas have been developed that optimally match the
      shape of the naso-frontal communication. An approach is proposed to the choice of
      the most adequate instrument for endonasal probing frontal sinuses.

PMID- 21191343
TI  - [Comparative characteristic of different methods of conservative treatment of
      exudative rhinosinusitis].
AB  - The objective of the present study was to evaluate effectiveness of secretolytic,
      secreto-stimulating therapy in 40 patients presenting with acute rhinosinusitis.
      It was confirmed that acute inflammation results in suppression of local
      protective mechanisms acting in nasal cavity mucosa. Secretolytic and anti
      inflammatory activity of Sinuforte was shown to induce these mechanisms; there is
      correlation between this effect and clinical picture of the disease. Parallel
      analysis of the results of traditional treatment of sinusitis and secretolytic,
      secretion-stimulating therapy has demonstrated high efficiency of the latter
      modality in patients suffering acute rhinosinusitis.

PMID- 21191344
TI  - [Comparative analysys of immunocorrective effect of ultraviolet irradiation of
      autoblood and plasmapheresis in patients with recurrent polypous rhinosinusitis].
AB  - The objective of the present study was to evaluate the immune status of patients
      with chronically recurring polypous rhinosinusitis (CRPS) for the identification
      of the key markers of immune disorders. Assessment of the efficiency of
      traditional therapy during the postoperative period demonstrated that it was very
      low in terms of beneficial effect on the major components of the immune system, T
      and B lymphocytes. Determination of the frequency of immune disorders during
      irradiation of autoblood with ultraviolet light and plasmapheresis in the
      postoperative period and evaluation of "true" effects of these treatments
      revealed their significant quantitative immunostimulating action. Integral
      evaluation (rank-sum analysis) demonstrated similar therapeutic efficiency of the
      two methods.

PMID- 21191345
TI  - [Surgical rehabilitation of patients presenting with chronic suppurative otitis
      media].
AB  - The purpose of the present study was to elucidate the character of complications
      following divided atticoanthrotomy with tympanoplasty in patients presenting with
      chronic suppurative otitis media (CSOM) and mucositis in the late postoperative
      period. It was shown that the most common causes of hearing impairment were
      atelectasis and perforation of the neotympanic membrane within 5 years after
      surgery, formation of retraction pockets and even cholesteatoma at later time
      points in the postoperative period. Adequately scheduled rehabilitative measures
      including conservative and surgical treatment made it possible to restore hearing
      in 76% of the previously operated patients. Those who applied for medical aid at
      a later time (6-15 years after surgery) and developed, in addition, retraction
      pockets and cholesteatomas or experienced elevation of the acoustic perception
      threshold failed to reach the level of hearing they had had soon after primary
      surgery. It is concluded that patients who underwent closed-type sanation
      reconstructive surgery should be referred for dispensary observation in order to
      prevent the development of cicatrization processes in the tympanic cavity,
      retraction of the tympanic membrane, and reactivation of the inflammatory
      catarrhal process in middle- ear cavities.

PMID- 21191346
TI  - [Combined approaches to diagnostics and treatment of traumatic otitis].
AB  - A total of 216 patients with the injured tympanic membrane were examined and
      treated during the last 5 years. 198 (91.6%) patients presenting with traumatic
      otitis were found to have pathological changes in the nose and paranasal sinuses.
      In patients who applied for medical aid soon (within 1-2 weeks) after injury to
      the tympanic membrane, the resulting perforation was closed with the use of hen's
      egg amniotic membrane. Audiological examination demonstrated that 84.7% of
      traumatic tympanic membrane ruptures were associated with acute sensorinerual
      loss of hearing.

PMID- 21191347
TI  - [Functional results of "open" and "closed" surgery on the middle ear].
AB  - This paper was designed to evaluate functional results of "open" and "closed"
      type surgery on the middle ear in 186 patients presenting with chronic
      suppurative otitis media. Audiological examination was performed 1, 3, and 5
      years after surgery. Analysis of outcomes of "open" and "closed"-type operations
      did not reveal significant differences in the degree of improvement of hearing
      and speech perception. It means that neither intact posterior wall of the
      auditory passage nor its removal has appreciable effect on the hearing function.

PMID- 21191348
TI  - [Potential of fibrolaryngoscopy for the improvement of diagnosis of laryngeal
      diseases].
AB  - The objective of the present study was to analyse results of fibrolaryngoscopic
      examination of pretumorous and tumorous laryngeal structures in 75 patients aged
      from 17 to 78 years who underwent repeated laryngeal biopsies to confirm
      suspected diagnosis of cancer. Vital staining of affected mucosal areas with a 1%
      methylene blue solution was used for the purpose. It was found that malignant
      tumours coloured violet as they readily absorbed the dye while its fixation by
      dysplastic tissue produced all shades of blue depending on the degree of
      dysplasia. It is concluded that the method employed in this study increases the
      informative value of clinical and histological diagnosis and thereby permits to
      avoid the use of additional diagnostic procedures.

PMID- 21191349
TI  - [Effectiveness criteria for the topical application of glucocorticosteroids to
      the treatment of exudative otitis media associated with allergic rhinitis].
AB  - We undertook comparative analysis of ciliotoxic effect of glucocorticosteroids
      frequently used for catheterization of the eustachian tube in patients presenting
      with exudative otitis media and concomitant allergic rhinitis. It was shown that
      the recovery of transport function of ciliary epithelium and appreciable clinical
      effect of the treatment were achieved by the application of mometasone furoate.
      Dexamethasone was next to mometasone in terms of efficiency whereas
      hydrocortisone produced much lower beneficial effect. It is concluded that,
      taking into account high bioavailability of dexametasone and hydrocortisone (>
      80%) and contraindications to their intranasal administration, the preference
      should be given to medications with lower bioavailability.

PMID- 21191350
TI  - [Improved diagnosis of the severity of chronic decompensated tonsillitis].
AB  - Results of examination and treatment of 111 patients were used to evaluate the
      severity of chronic decompensated tonsillitis based on the following parameters
      of endotoxicosis: leukocytic intoxication index, content of medium molecular
      weight peptides in blood, and erythrocyte sorption capacity. These results
      provided additional information about the functional state of palatine tonsils
      and severity of tonsillogenic intoxication; moreover they made it possible to
      evaluate efficiency of conservative treatment and determine indications for
      surgical intervention. Taken together, these data may be used to avoid subjective
      conclusions as regards the degree of decompensation in patients with chronic
      tonsillitis.

PMID- 21191351
TI  - [Immune status of patients with exacerbation of chronic suppurative otitis media
      and its correction].
AB  - The authors report results of a clinical and immunological study involving 38
      patients with exacerbation of chronic suppurative otitis media. It has
      demonstrated high immunological and clinical efficiency of combined treatment
      with derinate (an agent stimulating local immunity) and high molecular-weight
      polypeptide polyoxidonium. It is concluded that inclusion of these drugs in
      combined therapy of chronic suppurative otitis media increases its immunological
      and clinical effectiveness and allows duration of patients' hospitalization to be
      reduced.

PMID- 21191352
TI  - [Assessment of immune disorders in patients presenting with various forms of
      chronic suppurative otitis media in the postoperative period].
AB  - The present study was designed for immunological examination of 46 patients
      presenting with various forms of chronic suppurative otitis media. All the
      patients underwent surgical intervention on mastoid process (processus
      mastoideus). It was shown that exacerbation of catarrhal inflammation provoked a
      significant decrease of the total lymphocyte, T-helpers, and B-lymphocyte (CD22)
      count whereas the concentration of T-suppressors increased. In patients with the
      distractive form of chronic suppurative otitis media, the absolute number of
      total lymphocytes, T-lymphocytes, T-helpers, and B-lymphocytes was also reduced
      while the concentration of IgG was elevated. The level of serum cytokines (IL-1
      beta, IL-6, TNF-alpha) increased in both forms of the disease although the rise
      in case of catarrhal inflammation was much more pronounced. These data suggest
      beneficial effect of supplemental corrective immunotherapy.

PMID- 21191353
TI  - [Peculiarities of the treatment of patients presenting with chronic suppurative
      otitis media associated with Gram-negative microorganisms].
AB  - The objective of the present study was to determine the absolute and relative
      numbers of T-lymphocytes, B-lymphocytes, T-suppressors, T-helpers, phagocytes,
      immunoglobulins A, M, and G in blood sera of patients presenting with chronic
      suppurative otitis media who had undergone sanation surgery. The study included
      tests for the evaluation of immunological efficiency of combined treatment with
      imunofan and myelopid in 89 patients divided into two groups. Pretreatment
      immunological status of all patients was characterized by reduced B-lymphocyte, T
      helper, and phagocyte counts coupled to the elevated levels of IgM and T
      suppressors. Patients of group 1 received conventional antibacterial therapy,
      those in group 2 were treated with a combination of imunofan and myelopid.
      Conventional therapy failed to correct immune deficiency. Additional treatment
      with a combination of imunofan and myelopid following sanation surgery proved to
      be much more efficacious. This observation was confirmed by the results of
      clinical, cytological, and immunological studies.

PMID- 21191354
TI  - [Efficiency of combination therapy for acute otitis media].
AB  - The clinical efficiency of treatment was evaluated in 60 patients aged 18 to 60
      years with protracted acute otitis media (AOM) who had residual tympanic membrane
      inflammation and exudates in the tympanic cavity. The patients were divided into
      2 groups of 30 each, who received equal basic medical treatment; Group 1 patients
      were additionally given eurespal (fenspiride) 80 mg thrice daily for 2 weeks. The
      patients were examined by clinical, endoscopic, and audiometric studies; the
      transport function of the nasal ciliated epithelium was also explored. The
      findings suggest the benefits of the additional use of eurespal in the treatment
      of the catarrhal stage of AOM.

PMID- 21191355
TI  - [Specific features of surgical anatomy of the subhyoid region with special
      reference to tracheostomy].
AB  - Peculiarities of thyroid gland linear dimensions, volume, shape, and
      topographical features were investigated using the morphological material
      obtained from 426 human corpses of either gender with a view to using this
      information for planning and performing tracheostomy in residents of the Central
      Chernozem region, Russia. The study yielded new data on surgical anatomy of
      additional muscles of the subhyoid region, thyroid isthmus and pyramidal lobe.
      Rare and previously unknown variants of anatomical structure of the anterior
      cervical area are described that may play the role of risk factors of
      postoperative complications of tracheostomy. Relevant recommendations are
      provided for practicing otorhinolaryngologists.

PMID- 21191356
TI  - [Morphological substantiation of surgical sanation of the ethmoidal labyrinth in
      patients with inflammatory pathology of frontal sinuses].
AB  - This study had the objective of evaluating intraoperative characteristics of
      sanation surgery for the correction of structural elements of ethmoid bone in 131
      patients presenting with frontitis. Moreover, it included histological
      examination of the resected tissues. It was shown that chronic frontitis is
      associated not only with serious morphological changes in mucous membrane of the
      respective frontal sinusis and along the entire length of ethmoidal labyrinth but
      also with necrobiotic processes in the ethmoid bone plates, depending on the
      state of the ostiomeatal complex. It is supposed that these findings may account
      for irregular or low effect of conservative therapy of chronic frontitis and
      confirm the necessity of surgical sanation of ethmoidal labyrinth with due regard
      for the state of the ostiomeatal complex.

PMID- 21191357
TI  - [Diagnostic criteria for surgical correction of exudative otitis media in
      children].
AB  - A total of 118 children with exudative otitis media were available for
      observation in this study. Pneumatization of the mastoid process was evaluated by
      the roentgenoplanimetric technique. A large fraction of patients (48%) with acute
      exudatived otitis media showed pneumatic type of pneumatization whereas sclerotic
      pneumatization predominated in children with chronic exudative otitis media
      (68%). Retractions significantly more frequently developed in ears with the
      sclerotic type of pneumatization of the mastoid process (91%) than in case of
      pneumatic pneumatization. Based on these data, the children were divided into two
      groups, one comprising 25 patients with acute exudative otitis, the other 35 ones
      with recurrent disease. It is concluded that children with the symptomocomplex
      characterized by low level of pneumatization of the mastoid process, conductive
      or mixed hearing loss with a bone-air interval of 30-50 dB, and type B
      tympanogram are in need of early surgical intervention.

PMID- 21191358
TI  - [Combined therapy of sensorineural loss of hearing].
AB  - The objective of the present study was to evaluate the efficiency of
      meatotympanal blockade by neuromedin (ipidacrine) included in the combined
      treatment of sensorineraul loss of hearing. This therapy was given to 95 patients
      with sensorineural hearing loss of vascular origin who reported strong
      tympanophony. Results of audiological examination and ultrasound dopplerography
      as well as the patients' subjective feeling provided data for the conclusion that
      medicamentous therapy of sensorineural loss of hearing produces the best effect
      if combined with meatotympanal blockade by 1 ml (15 mg) of a 1% neuromedine
      solution during 10 days.

PMID- 21191359
TI  - [Possibilities and prospects for surgical obliteration of frontal sinuses with
      the use of osteoplastic MK-9M glue composition in patients with chronically
      recurring and post-traumatic frontitis].
AB  - This study included analysis of the results of treatment of 136 patients at the
      age from 19 to 92 years presenting with pathological changes in the frontal
      sinuses. 126 of them had undergone surgery for the treatment of inflammatory
      diseases, osteomas, and injuries to the frontal sinuses in the preceding period.
      62.7% of the patients in the latter group developed relapses of the disease;
      therefore, 44.1% of them needed the second operation. In order to improve the
      efficiency of treatment of chronic recurrent and postoperative frontitis, radical
      operation on the frontal sinuses in 56 patients was completed by obliteration of
      the sinus using the osteoplastic composite material MK-9M. Dynamic observations
      during the three subsequent years demonstrated stable recovery in all the 56
      patients.

PMID- 21191360
TI  - [New macrolides or a promise for noninvasive treatment in patients with acute
      bacterial sinusitis].

PMID- 21191361
TI  - Mycophenolate mofetil-based immunosuppression with sirolimus in renal
      transplantation: a randomized, controlled Spare-the-Nephron trial.
AB  - As part of the Spare-the-Nephron trial, we evaluated the combination
      mycophenolate mofetil (MMF) and sirolimus (SRL) as a calcineurin inhibitor (CNI)
      free regimen for the preservation of renal function in renal allograft
      recipients. This 2-year, open-label, multicenter trial randomized 299 patients of
      which 151 were maintained on MMF and a CNI, 148 on MMF plus SRL (n=120,
      tacrolimus; n=31, cyclosporine). Baseline characteristics including measured
      (iothalamate) glomerular filtration rate (GFR) were similar between groups. After
      1 year, the mean percentage change from baseline in the primary end point of
      measured GFR was significantly higher in the MMF/SRL group compared with the
      MMF/CNI group. After 2 years, the change was indistinguishable. Calculated
      creatinine clearance and GFR were significantly greater with MMF/SRL at 2 years
      within which biopsy-proven acute rejection (BPAR) occurred in 14 MMF/SRL-treated
      patients (3 graft losses) and in 17 receiving the MMF/CNI (6 graft losses).
      Significantly, no patients receiving MMF/SRL but five treated with MMF/CNI died.
      Thus, compared with MMF/CNI treatment, a 2-year regimen of MMF/SRL resulted in
      similar measures of renal function but with fewer deaths and a trend to less BPAR
      and graft loss.

PMID- 21191362
TI  - Increased protein intake augments kidney volume and function in healthy infants.
AB  - Protein intake has been directly associated with kidney growth and function in
      animal and human observational studies. Protein supply can vary widely during the
      first months of life, thus promoting different kidney growth patterns and
      possibly affecting kidney and cardiovascular health in the long term. To explore
      this further, we examined 601 healthy 6-month-old formula-fed infants who had
      been randomly assigned within the first 8 weeks of life to a 1-year program of
      formula with low-protein (LP) or high-protein (HP) contents and compared them
      with 204 breastfed (BF) infants. At 6 months, infants receiving the HP formula
      had significantly higher kidney volume (determined by ultrasonography) and ratios
      of kidney volume to body length and kidney volume to body surface area than did
      infants receiving the LP formula. BF infants did not differ from those receiving
      the LP formula in any of these parameters. Infants receiving the HP formula had
      significantly higher serum urea and urea to creatinine ratios than did LP formula
      and BF infants. Hence, in this European multicenter clinical trial, we found that
      a higher protein content of the infant formula increases kidney size at 6 months
      of life, whereas a lower protein supply achieves kidney size indistinguishable
      from that of healthy BF infants. The potential long-term effects of a higher
      early protein intake on long-term kidney function needs to be determined.

PMID- 21191364
TI  - Welcome to the fourth year of Mucosal Immunology!

PMID- 21191366
TI  - Preassembled zinc-finger arrays for rapid construction of ZFNs.

PMID- 21191367
TI  - Live-cell dSTORM with SNAP-tag fusion proteins.

PMID- 21191368
TI  - Optogenetics.

PMID- 21191369
TI  - From cudgel to scalpel: toward precise neural control with optogenetics.

PMID- 21191370
TI  - The promise of optogenetics in cell biology: interrogating molecular circuits in
      space and time.

PMID- 21191371
TI  - Channelrhodopsin engineering and exploration of new optogenetic tools.

PMID- 21191372
TI  - Screening: the age of fishes.

PMID- 21191373
TI  - Zinc-finger nucleases transition to the CoDA.

PMID- 21191374
TI  - At last, functional glycomics.

PMID- 21191375
TI  - Seeing is believing.

PMID- 21191376
TI  - Assemblies: the good, the bad, the ugly.

PMID- 21191377
TI  - Rifampin's acute inhibitory and chronic inductive drug interactions: experimental
      and model-based approaches to drug-drug interaction trial design.
AB  - We studied the time course for the reversal of rifampin's effect on the
      pharmacokinetics of oral midazolam (a cytochrome P450 (CYP) 3A4 substrate) and
      digoxin (a P-glycoprotein (P-gp) substrate). Rifampin increased midazolam
      metabolism, greatly reducing the area under the concentration-time curve (AUC(0
      infinity)). The midazolam AUC(0-infinity) returned to baseline with a half-life
      of ~8 days. Rifampin's effect on the AUC(0-3 h) of digoxin was biphasic: the
      AUC(0-3 h) increased with concomitant dosing of the two drugs but decreased when
      digoxin was administered after rifampin. Digoxin was found to be a weak substrate
      of organic anion-transporting polypeptide (OATP) 1B3 in transfected cells.
      Although the drug was transported into isolated hepatocytes, it is not likely
      that this transport was through OATP1B3 because the transport was not inhibited
      by rifampin. However, rifampin did inhibit the P-gp-mediated transport of digoxin
      with a half-maximal inhibitory concentration (IC(50)) below anticipated gut lumen
      concentrations, suggesting that rifampin inhibits digoxin efflux from the
      enterocyte to the intestinal lumen. Pharmacokinetic modeling suggested that the
      effects on digoxin are consistent with a combination of inhibitory and inductive
      effects on gut P-gp. These results suggest modifications to drug-drug interaction
      (DDI) trial designs.

PMID- 21191378
TI  - Translational pharmacokinetics and pharmacodynamics of an FcRn-variant anti-CD4
      monoclonal antibody from preclinical model to phase I study.
AB  - MTRX1011A is a humanized anti-CD4 antibody with an amino acid substitution
      (N434H) to improve its binding to the neonatal Fc receptor (FcRn).
      Pharmacokinetic/pharmacodynamic (PK/PD) data in baboons suggest that the
      increased binding to FcRn reduces the nonspecific elimination rate (K(el)) of
      MTRX1011A by ~50% but does not affect its PK-PD relationship. The human PK/PD
      data of MTRX1011A from a phase I study in patients with rheumatoid arthritis (RA)
      were compared with those previously reported for TRX1, its predecessor antibody,
      using population PK-PD modeling. The results suggest a comparable PK-PD
      relationship and no significant difference between the K(el) values of the two
      antibodies. However, the results may have been confounded by the differences in
      the clinical populations in which the two antibodies were studied and the
      presence of preexisting immunoglobulin M (IgM) antibodies in the RA sera that
      recognize N434H in MTRX1011A. This study highlights the challenges in translating
      from animal studies to human application the effects of FcRn-directed mutations
      on the PK of monoclonal antibodies.

PMID- 21191379
TI  - Population pharmacokinetics of sulfadoxine and pyrimethamine in Malawian children
      with malaria.
AB  - In addition to parasite resistance, inadequate levels of exposure to antimalarial
      drugs may contribute to treatment failure. We developed population
      pharmacokinetic (PK) models to describe the distribution of sulfadoxine (SDX) and
      pyrimethamine (PYM) in children with uncomplicated malaria in Malawi. The
      concentration levels of antimalarial drugs in whole blood were determined using
      high-performance liquid chromatography. We found no evidence of underdosing in
      children as compared with adults; the children had drug exposure levels similar
      to those described in adults. Treatment failure was more likely in children with
      lower PYM concentrations on day 14 (P = 0.024), and there was a trend for lower
      SDX concentrations on day 14 (P = 0.061). SDX and PYM concentrations at levels
      predictive of treatment failure have been identified at day 14. Less than one
      third of the children displayed drug concentration levels above these thresholds
      after receiving the recommended SDX-pyrimethamine (SP) dose. Our findings suggest
      that PK factors contributed to the observed high rate of treatment failure, and
      we therefore recommend a higher SP dose for children under the age of 5 years.

PMID- 21191380
TI  - Quantification of cerebral blood flow as biomarker of drug effect: arterial spin
      labeling phMRI after a single dose of oral citalopram.
AB  - Arterial spin labeling (ASL) allows noninvasive quantification of cerebral blood
      flow (CBF), which can be used as a biomarker of drug effects in pharmacological
      magnetic resonance imaging (phMRI). In a double-blind, placebo-controlled
      crossover study, we investigated the effects of a single oral dose of citalopram
      (20 mg) on resting CBF in 12 healthy subjects, using ASL phMRI. Support-vector
      machine (SVM) analysis detected significant drug-induced reduction in CBF in
      brain regions including the amygdala, fusiform gyrus, insula, and orbitofrontal
      cortex. These regions have been shown to have abnormally elevated CBF in patients
      with major depression, as well as in subjects genetically prone to depression.
      Mixed-effects analysis on data extracted from selected regions of interest (ROIs)
      revealed significant drug effect only in serotonergic areas of the brain (z = 
      4.45, P < 0.005). These results demonstrate the utility of ASL phMRI as a
      biomarker of pharmacological activity of orally administered drugs in the brain.

PMID- 21191381
TI  - Applications of physiologically based pharmacokinetic (PBPK) modeling and
      simulation during regulatory review.
AB  - Physiologically based pharmacokinetic (PBPK) modeling and simulation is a tool
      that can help predict the pharmacokinetics of drugs in humans and evaluate the
      effects of intrinsic (e.g., organ dysfunction, age, genetics) and extrinsic
      (e.g., drug-drug interactions) factors, alone or in combinations, on drug
      exposure. The use of this tool is increasing at all stages of the drug
      development process. This report reviews recent instances of the use of PBPK in
      decision-making during regulatory review. The examples are based on Center for
      Drug Evaluation and Research reviews of several submissions for investigational
      new drugs (INDs) and new drug applications (NDAs) received between July 2008 and
      June 2010. The use of PBPK modeling and simulation facilitated the following
      types of decisions: the need to conduct specific clinical pharmacology studies,
      specific study designs, and appropriate labeling language. The report also
      discusses the challenges encountered when PBPK modeling and simulation were used
      in these cases and recommends approaches to facilitating full utilization of this
      tool.

PMID- 21191382
TI  - Pharmaceutical innovation in the 21st century: new drug approvals in the first
      decade, 2000-2009.
AB  - The first decade of the 21st century was a challenging period for the pharma
      sector and could prove to be a turning point in the evolution of the industry. We
      examine drug development performance metrics for new product approvals during
      2000-2009 and compare them with those of the prior two decades. The results
      indicate that, whereas total approvals are currently at a 25-year low, the
      percentage of priority products is nearly 50% of the total--a 30-year high.
      Following enactment of the Prescription Drug Use Fee Act of 1992 (PDUFA), the
      mean duration of the approval phases of drug development declined by more than 1
      year over the 30-year period--to a low of 1.2 years in 2005-2009--whereas the
      duration of the clinical phases increased. The longer clinical phases were due,
      in part, to a greater number of approved central nervous system (CNS) and
      antineoplastic agents, two therapeutic classes with relatively long average
      development times (8.1 and 6.9 years, respectively). The results provide the
      underpinnings of a fundamental shift in the structure of the research-based
      industry.

PMID- 21191383
TI  - Biclustering of adverse drug events in the FDA's spontaneous reporting system.
AB  - In this article, we present a new pharmacovigilance data mining technique based
      on the biclustering paradigm, which is designed to identify drug groups that
      share a common set of adverse events (AEs) in the spontaneous reporting system
      (SRS) of the US Food and Drug Administration (FDA). A taxonomy of biclusters is
      developed, revealing that a significant number of bona fide adverse drug event
      (ADE) biclusters have been identified. Statistical tests indicate that it is
      extremely unlikely that the bicluster structures thus discovered, as well as
      their content, could have arisen by mere chance. Some of the biclusters
      classified as indeterminate provide support for previously unrecognized and
      potentially novel ADEs. In addition, we demonstrate the potential importance of
      the proposed methodology in several important aspects of pharmacovigilance such
      as providing insight into the etiology of ADEs, facilitating the identification
      of novel ADEs, suggesting methods and a rationale for aggregating terminologies,
      highlighting areas of focus, and providing an exploratory tool for data mining.

PMID- 21191384
TI  - State of the controlled clinical trial enterprise in the United States.
AB  - We undertook a survey of the current capability in the United States to conduct
      controlled clinical trials. The intention was to use the results as a foundation
      for understanding how to create a controlled clinical trial capability sufficient
      to meet future needs of US health care. For this purpose, using the results from
      an advanced search of ClinicalTrials.gov on 16 August 2009, we created a database
      consisting of actively recruiting interventional trials having at least one US
      investigator center. As of 16 August 2009, there were 10,974 actively recruiting
      interventional trials having at least one investigator center in the United
      States. These trials were seeking to recruit a total of 2.8 million subjects. Of
      the trials, 68% involved the study of drugs or biologicals. The data indicate
      that clinical research conducted in the United States is dominated by research on
      regulated products. We estimated that 1 of every 200 persons in the United States
      would need to participate as a subject in a clinical trial if the current
      clinical research portfolio is to be successfully completed.

PMID- 21191387
TI  - Getting the urine to the lab: time to think outside of the specimen cup.
AB  - Rucker and colleagues examine the relationship between distance to a nephrologist
      and the likelihood of seeing a nephrologist. They demonstrate that increasing
      distance from a nephrologist has a 'protective effect' against seeing a
      nephrologist and is associated with a greater risk of hospitalization, a longer
      hospitalization, and a greater mortality risk. Implications of these associations
      as well as the mechanisms supporting them are explored.

PMID- 21191388
TI  - Prevention of sudden cardiac arrest in dialysis patients: can we do more to
      improve outcomes?
AB  - Sudden cardiac arrest (SCA) is a leading cause of cardiac-associated mortality in
      dialysis patients. Risk factors unique to hemodialysis patients include abnormal
      electrolytes, large-volume ultrafiltration, and prior history of cardiac disease.
      Few randomized controlled trials of standard cardiac interventions have been
      completed in dialysis patients. Observational studies suggest that modification
      of the dialysis prescription may be one place to intervene. Prospective research
      is needed to determine mechanisms of SCA in hemodialysis patients.

PMID- 21191389
TI  - Am I my brother's keeper?: fratricide in the kidney.
AB  - Experimental acute kidney injury (AKI) is accompanied by the death of renal
      tubule epithelial cells, necrosis and apoptosis of the terminal portion of the
      proximal tubule, and apoptosis in the distal nephron. While immune competent
      cells invading the kidney play a role in such cell death, intervention in these
      processes only partially ameliorates the extent of cell death. Given the results
      of Linkermann et al. in this issue of KI, an epithelium-derived component of
      immune mediated cell death must now be strongly considered.

PMID- 21191390
TI  - TWEAK-Fn14 as a mediator of acute kidney injury.
AB  - Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor,
      fibroblast growth factor-inducible 14 (TWEAK-Fn14), are widely expressed and are
      involved in both injury and repair. Hotta et al. now demonstrate an important
      role for Fn14 in the common clamp ischemia model of acute kidney injury. Their
      data suggest paracrine and autocrine effects in which TWEAK produced by tubule
      cells feeds back on them via upregulated Fn-14 receptors expressed downstream in
      the proximal tubule.

PMID- 21191391
TI  - Coronary artery calcification and cardiovascular mortality in predialysis
      patients.

PMID- 21191392
TI  - Recurrent tartaric acid acidosis?

PMID- 21191395
TI  - Reninoma.

PMID- 21191396
TI  - Patients' preference in the treatment of erectile dysfunction: a critical review
      of the literature.
AB  - The increase in the number of safe and effective ED treatments highlights the
      importance of patients' preference when choosing a therapeutic option. Several
      studies assessing these preferences are now available in published literature.
      This article aims to review and discuss the studies on patients' preference and
      the data concerning the reasons for preference for one PDE-5 inhibitor over
      another. A PubMed search was conducted for manuscripts published within the last
      10 years containing the search items ED, preference, sildenafil, tadalafil or
      vardenafil. Selected articles were discerningly reviewed and summarized (design,
      limitations and relevance). The articles selected were peer reviewed publications
      on patients' preference and ED published in medical literature since 2000.
      Preference studies that include either two (tadalafil and sildenafil) or three
      PDE-5 inhibitors (tadalafil, sildenafil and vardenafil), showed that the majority
      of the patients preferred tadalafil versus either vardenafil or sildenafil. As
      the treatment of ED has evolved, patients' preference has become an important
      aspect of ED therapy, 52-65% of patients prefer tadalafil versus 12-20%
      vardenafil or 8-30% sildenafil. All founded studies have serious limitations,
      particularly in terms of dosing differences. Preference for tadalafil was mainly
      because of the longer duration of action that increases patients' freedom in
      sexual life. There is a consistency in patients' preference for tadalafil over
      sildenafil or vardenafil across the studies reviewed.

PMID- 21191397
TI  - Question for a questionnaire: the International Index of Erectile Function.
AB  - The aim of this study was to analyze the impact of patient age and education
      level on the comprehension of the Turkish version of Index of Erectile Function
      (IIEF), and to determine the patient characteristics that make this questionnaire
      less reliable. In this study, 238 male patients presenting to our clinic were
      enrolled. The patients were asked to complete the Turkish version of the IIEF
      questionnaire upon arrival by themselves and then once again during their second
      visit with the assistance of a physician. 'Accurate' comprehension of the IIEF
      was considered to be the consistency between the 'self-administered' and
      'physician-assisted' IIEF scores. The impact of patient age and education level
      on the 'accurate' comprehension of the IIEF was analyzed. There was a significant
      difference between the 'self-administered' and 'physician-assisted' IIEF scores
      in patients >= 60 years of age (P=0.045) and primary school graduates (P=0.015).
      Age >= 60 years and being primary school graduate are factors lowering the
      comprehension of the Turkish version of the IIEF by the patients. Older patients
      and patients with lower education could benefit from the assistance of a
      physician while completing this questionnaire.

PMID- 21191398
TI  - Human hair follicle and epidermal melanocytes exhibit striking differences in
      their aging profile which involves catalase.

PMID- 21191399
TI  - The nude mutant gene Foxn1 is a HOXC13 regulatory target during hair follicle and
      nail differentiation.
AB  - Among the Hox genes, homeobox C13 (Hoxc13) has been shown to be essential for
      proper hair shaft differentiation, as Hoxc13 gene-targeted (Hoxc13(tm1Mrc)) mice
      completely lack external hair. Because of the remarkable overt phenotypic
      parallels to the Foxn1(nu) (nude) mutant mice, we sought to determine whether
      Hoxc13 and forkhead box N1 (Foxn1) might act in a common pathway of hair follicle
      (HF) differentiation. We show that the alopecia exhibited by both the
      Hoxc13(tm1Mrc) and Foxn1(nu) mice is because of strikingly similar defects in
      hair shaft differentiation and that both mutants suffer from a severe nail
      dystrophy. These phenotypic similarities are consistent with the extensive
      overlap between Hoxc13 and Foxn1 expression patterns in the HF and the nail
      matrix. Furthermore, DNA microarray analysis of skin from Hoxc13(tm1Mrc) mice
      identified Foxn1 as significantly downregulated along with numerous hair keratin
      genes. This Foxn1 downregulation apparently reflects the loss of direct
      transcriptional control by HOXC13 as indicated by our results obtained through co
      transfection and chromatin immunoprecipitation (ChIP) assays. As presented in the
      discussion, these data support a regulatory model of keratinocyte differentiation
      in which HOXC13-dependent activation of Foxn1 is part of a regulatory cascade
      controlling the expression of terminal differentiation markers.

PMID- 21191400
TI  - Functional interplay between mitochondrial and proteasome activity in skin aging.
AB  - According to the mitochondrial theory of aging, reactive oxygen species (ROS)
      derived primarily from mitochondria cause cumulative oxidative damage to various
      cellular molecules and thereby contribute to the aging process. On the other
      hand, a pivotal role of the proteasome, as a main proteolytic system implicated
      in the degradation of oxidized proteins during aging, is suggested. In this
      study, we analyzed mitochondrial function in dermal fibroblasts derived from
      biopsies obtained from healthy young, middle-aged, and old donors. We also
      determined proteasome activity in these cells, using a degron-destabilized green
      fluorescent protein (GFP)-based reporter protein. We found a significant decrease
      in mitochondrial membrane potential in samples from aged donors, accompanied by a
      significant increase in ROS levels. Respiratory activity was not significantly
      altered with donor age, probably reflecting genetic variation. Proteasome
      activity was significantly decreased in fibroblasts from middle-aged donors
      compared with young donors; fibroblasts derived from the oldest donors displayed
      a high heterogeneity in this assay. We also found intraindividual coregulation of
      mitochondrial and proteasomal activities in all human fibroblast strains tested,
      suggesting that both systems are interdependent. Accordingly, pharmacological
      inhibition of the proteasome led to decreased mitochondrial function, whereas
      inhibition of mitochondrial function in turn reduced proteasome activity.

PMID- 21191401
TI  - Human and mouse mast cells express and secrete the GPI-anchored isoform of CD160.
AB  - CD160 is expressed by human and mouse natural killer (NK) cells and other
      cytotoxic lymphocyte subpopulations. CD160 is mostly expressed as a trimeric 83
      kDa glycosylphosphatidylinositol (GPI)-anchored activating NK receptor, cleaved
      upon IL-15 stimulation in a secreted trimeric soluble form (sCD160) that binds to
      major histocompatibility complex (MHC) class I molecules, while a transmembrane
      isoform appears. sCD160 exhibits immunoregulatory function as it inhibits CD8(+)
      T-lymphocyte cytotoxic activity. We show that human mast cells (MCs) express
      CD160. In human and mouse skin, resident MCs expressed CD160, whereas in C57BL/6
      Kit(W-sh/W-sh) mice, CD160(+) cells were only identified at the site of
      reconstitution with syngeneic cultured MCs. In the human mast cell line, HMC-1,
      we only identified the transcripts of the GPI-anchored CD160 isoform.
      Furthermore, CD160 was identified in HMC-1 and mouse MC supernatants, suggesting
      that MCs release sCD160. Supporting this hypothesis, HMC-1 express the GPI
      specific phospholipase D variant 2 involved in the NK lymphocyte membrane
      cleavage of CD160, and morphological studies highlighted a relative loss of CD160
      expression in inflammatory skin sites, where MC degranulation is expected to
      occur. We also demonstrated an inhibition of T-cell cytotoxicity by HMC-1
      supernatant that was partially reversed by anti-CD160 mAb. In conclusion, sCD160,
      produced by MCs, may have a role in T-cell-MC interactions in vivo.

PMID- 21191402
TI  - Zebrafish: a model system to study heritable skin diseases.
AB  - Heritable skin diseases represent a broad spectrum of clinical manifestations due
      to mutations in ~500 different genes. A number of model systems have been
      developed to advance our understanding of the pathomechanisms of genodermatoses.
      Zebrafish (Danio rerio), a freshwater vertebrate, has a well-characterized
      genome, the expression of which can be easily manipulated. The larvae develop
      rapidly, with all major organs having developed by 5-6 days post-fertilization,
      including the skin, consisting of the epidermis comprising two cell layers and
      separated from the dermal collagenous matrix by a basement membrane. This
      perspective highlights the morphological and ultrastructural features of
      zebrafish skin, in the context of cutaneous gene expression. These observations
      suggest that zebrafish provide a useful model system to study the molecular
      aspects of skin development, as well as the pathogenesis and treatment of select
      heritable skin diseases.

PMID- 21191403
TI  - Noninvasive in vivo imaging to evaluate immune responses and antimicrobial
      therapy against Staphylococcus aureus and USA300 MRSA skin infections.
AB  - Staphylococcus aureus skin infections represent a significant public health
      threat because of the emergence of antibiotic-resistant strains such as
      methicillin-resistant S. aureus (MRSA). As greater understanding of protective
      immune responses and more effective antimicrobial therapies are needed, a S.
      aureus skin wound infection model was developed in which full-thickness scalpel
      cuts on the backs of mice were infected with a bioluminescent S. aureus
      (methicillin sensitive) or USA300 community-acquired MRSA strain and in vivo
      imaging was used to noninvasively monitor the bacterial burden. In addition, the
      infection-induced inflammatory response was quantified using in vivo fluorescence
      imaging of LysEGFP mice. Using this model, we found that both IL-1alpha and IL
      1beta contributed to host defense during a wound infection, whereas IL-1beta was
      more critical during an intradermal S. aureus infection. Furthermore, treatment
      of a USA300 MRSA skin infection with retapamulin ointment resulted in up to 85
      fold reduction in bacterial burden and a 53% decrease in infection-induced
      inflammation. In contrast, mupirocin ointment had minimal clinical activity
      against this USA300 strain, resulting in only a 2-fold reduction in bacterial
      burden. Taken together, this S. aureus wound infection model provides a valuable
      preclinical screening method to investigate cutaneous immune responses and the
      efficacy of topical antimicrobial therapies.

PMID- 21191405
TI  - Development of quantitative molecular clinical end points for siRNA clinical
      trials.
AB  - RNA interference (RNAi) is an evolutionarily conserved mechanism that results in
      specific gene inhibition at the mRNA level. The discovery that short interfering
      RNAs (siRNAs) are selective, potent, and can largely avoid immune surveillance
      has resulted in keen interest to develop these inhibitors as therapeutics. A
      single nucleotide-specific siRNA (K6a_513a.12, also known as TD101) was recently
      evaluated in a phase 1b clinical trial for the rare skin disorder, pachyonychia
      congenita (PC). To develop a clinical trial molecular end point for this type of
      trial, methods were developed to: (1) isolate total RNA containing amplifiable
      mRNA from human skin and callus material; (2) quantitatively distinguish the
      single-nucleotide mutant mRNA from wild-type K6a mRNA in both patient-derived
      keratinocytes and patient callus; and (3) demonstrate that repeated siRNA
      treatment results in sustained inhibition of mutant K6a mRNA in patient-derived
      keratinocyte cultures. These methods allow noninvasive sampling and monitoring of
      gene expression from patient-collected shavings and may be useful in evaluating
      the effectiveness of RNAi-based therapeutics, including inhibitors that
      specifically target single-nucleotide mutations.

PMID- 21191406
TI  - Inflammatory peeling skin syndrome caused by a mutation in CDSN encoding
      corneodesmosin.

PMID- 21191404
TI  - Regulated proenkephalin expression in human skin and cultured skin cells.
AB  - Skin responds to environmental stressors via coordinated actions of the local
      neuroimmunoendocrine system. Although some of these responses involve opioid
      receptors, little is known about cutaneous proenkephalin expression, its
      environmental regulation, and alterations in pathology. The objective of this
      study was to assess regulated expression of proenkephalin in normal and
      pathological skin and in isolated melanocytes, keratinocytes, fibroblasts, and
      melanoma cells. The proenkephalin gene and protein were expressed in skin and
      cultured cells, with significant expression in fibroblasts and keratinocytes.
      Mass spectroscopy confirmed Leu- and Met-enkephalin in skin. UVR, Toll-like
      receptor (TLR)4, and TLR2 agonists stimulated proenkephalin gene expression in
      melanocytes and keratinocytes in a time- and dose-dependent manner. In situ
      Met/Leu-enkephalin peptides were expressed in differentiating keratinocytes of
      the epidermis in the outer root sheath of the hair follicle, in myoepithelial
      cells of the eccrine gland, and in the basement membrane/basal lamina separating
      epithelial and mesenchymal components. Met/Leu-enkephalin expression was altered
      in pathological skin, increasing in psoriasis and decreasing in melanocytic
      tumors. Not only does human skin express proenkephalin, but this expression is
      upregulated by stressful stimuli and can be altered by pathological conditions.

PMID- 21191407
TI  - In vivo imaging of human and mouse skin with a handheld dual-axis confocal
      fluorescence microscope.
AB  - Advancing molecular therapies for the treatment of skin diseases will require the
      development of new tools that can reveal spatiotemporal changes in the
      microanatomy of the skin and associate these changes with the presence of the
      therapeutic agent. For this purpose, we evaluated a handheld dual-axis confocal
      (DAC) microscope that is capable of in vivo fluorescence imaging of skin, using
      both mouse models and human skin. Individual keratinocytes in the epidermis were
      observed in three-dimensional image stacks after topical administration of near
      infrared (NIR) dyes as contrast agents. This suggested that the DAC microscope
      may have utility in assessing the clinical effects of a small interfering RNA
      (siRNA)-based therapeutic (TD101) that targets the causative mutation in
      pachyonychia congenita (PC) patients. The data indicated that (1) formulated
      indocyanine green (ICG) readily penetrated hyperkeratotic PC skin and normal
      callused regions compared with nonaffected areas, and (2) TD101-treated PC skin
      revealed changes in tissue morphology, consistent with reversion to nonaffected
      skin compared with vehicle-treated skin. In addition, siRNA was conjugated to NIR
      dye and shown to penetrate through the stratum corneum barrier when topically
      applied to mouse skin. These results suggest that in vivo confocal microscopy may
      provide an informative clinical end point to evaluate the efficacy of
      experimental molecular therapeutics.

PMID- 21191408
TI  - Regeneration of hair follicles is modulated by flightless I (Flii) in a rodent
      vibrissa model.
AB  - Regeneration of cells, tissues, and organs has long captured the attention of
      researchers for its obvious potential benefits in biomedical applications.
      Although mammals are notoriously poor at regeneration compared with many lower
      order species, the hair follicle, paradoxically a defining characteristic of
      mammals, is capable of regeneration following partial amputation. To investigate
      the role of a negative regulator of wound healing, flightless I (Flii), on hair
      follicle regeneration, the bulbar region of vibrissae from rats as well as
      strains of mice expressing low (Flii(+/-)), normal (Flii(+/+)), and high
      (FLII(Tg/Tg)) levels of Flii were surgically amputated, and then allowed to
      regenerate in vivo. Macroscopic and histological assessment of the regeneration
      process revealed impaired or delayed regenerative potential in Flii(+/-)
      follicles. Regenerated follicles expressing high levels of Flii (FLII(Tg/Tg))
      produced significantly longer terminal hair fibers. Immunohistochemical analysis
      was used to characterize the pattern of expression of Flii, as well as markers of
      hair follicle development and wound healing-associated factors during hair
      follicle regeneration. These studies confirmed that Flii appears to have a
      positive role in the regeneration of hair follicles, contrary to its negative
      influence on wound healing in skin.

PMID- 21191409
TI  - TP53 Arg72Pro polymorphism may have little involvement in the pathogenesis of
      skin cancer in Caucasians.

PMID- 21191410
TI  - Safety of topical corticosteroids in pregnancy: a population-based cohort study.
AB  - Topical corticosteroids may be indicated in pregnant women with skin conditions,
      but their safety in pregnancy is unclear. We used the UK General Practice
      Research Database to conduct a population-based cohort study to investigate
      whether maternal exposure to topical corticosteroids results in adverse pregnancy
      outcomes. We identified 35,503 pregnant women prescribed topical corticosteroids
      during the period from 85 days before last menstrual period (LMP) to delivery or
      fetal death and 48,630 unexposed women. We found no associations of maternal
      exposure to topical corticosteroids with orofacial cleft (and its two subtypes,
      i.e., cleft lip +/- palate (CLP) and cleft palate alone (CP)), preterm delivery,
      and fetal death (including miscarriage and stillbirth). The findings were similar
      when excluding exposure before LMP. In contrast, maternal exposure to potent/very
      potent topical corticosteroids shortly before and during pregnancy was
      significantly associated with fetal growth restriction (adjusted relative risk
      2.08; 95% confidence interval 1.40-3.10; number needed to harm, 168), which was
      confirmed by a significant dose-response relationship (P=0.025) and the
      sensitivity analysis excluding exposure before LMP. The increased risk for fetal
      growth restriction should be considered when prescribing potent/very potent
      topical corticosteroids to pregnant women, and appropriate obstetric care should
      be provided.

PMID- 21191411
TI  - Expression and function of the natural cytotoxicity receptor NKp46 on circulating
      malignant CD4+ T lymphocytes of Sezary syndrome patients.
AB  - The natural cytotoxicity receptors NKp30, NKp44, and NKp46 were identified as
      activating receptors mainly expressed by natural killer (NK) lymphocytes. In this
      study we show that peripheral blood malignant CD4(+) T lymphocytes from patients
      with Sezary syndrome, an aggressive form of cutaneous T-cell lymphoma, express
      NKp46 at their cell surface. Although NKp46 does not behave as an independent
      functional receptor, its engagement provides a strong inhibiting signal on the
      malignant T lymphocyte CD3-induced proliferation. We show that this inhibition is
      correlated with a decreased phosphorylation of the CD3zeta chain associated with
      NKp46 and/or the TCR/CD3 complexes. Our results reveal that in addition to
      KIR3DL2/CD158k expression, NKp46 could represent an additional marker on the
      circulating malignant T lymphocytes of Sezary patients, where it displays an as
      yet unreported function of inhibitory co-receptor able to interfere with the
      processes governing their CD3-dependent proliferation.

PMID- 21191412
TI  - Conditional activin receptor type 1B (Acvr1b) knockout mice reveal hair loss
      abnormality.
AB  - The in vivo functions of the activin A receptor type 1b (Acvr1b) have been
      difficult to study because Acvr1b(-/-) mice die during embryogenesis. To
      investigate the roles of Acvr1b in the epithelial tissues, we created mice with a
      conditional disruption of Acvr1b (Acvr1b(flox/flox)) and crossed them with K14
      Cre mice. Acvr1b(flox/flox); K14-Cre mice displayed various degrees of
      hairlessness at postnatal day 5, and the phenotype is exacerbated by age.
      Histological analyses showed that those hair follicles that developed during
      morphogenesis were later disrupted by delays in hair cycle reentry. Failure in
      cycling of the hair follicles and regrowth of the hair shaft and the inner root
      sheath resulted in subsequent severe hair loss. Apart from previous reports of
      other members of the transforming growth factor-beta/activin/bone morphogenic
      protein pathways, we demonstrate a specialized role for Acvr1b in hair cycling in
      addition to hair follicle development. Acvr1b(flox/flox); K14-Cre mice also had a
      thicker epidermis than did wild-type mice, which resulted from persistent
      proliferation of skin epithelial cells; however, no tumor formation was observed
      by 18 months of age. Our analysis of this Acvr1b knockout mouse line provides
      direct genetic evidence that Acvr1b signaling is required for both hair follicle
      development and cycling.

PMID- 21191413
TI  - Macrophage migration inhibitory factor is essential for eosinophil recruitment in
      allergen-induced skin inflammation.
AB  - Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine that has
      an essential role in the pathophysiology of experimental allergic inflammation.
      Recent findings suggest that MIF is involved in several allergic disorders,
      including atopic dermatitis (AD). In this study, the role of MIF in allergic skin
      inflammation was examined using a murine model of AD elicited by epicutaneous
      sensitization with ovalbumin (OVA). We observed the number of skin-infiltrating
      eosinophils to significantly increase in OVA-sensitized MIF transgenic (Tg) mice
      compared with their wild-type (WT) littermates. On the other hand, eosinophils
      were virtually absent from the skin of MIF knockout (KO) mice and failed to
      infiltrate their skin after repeated epicutaneous sensitization with OVA. The
      mRNA expression levels of eotaxin and IL-5 were significantly increased in OVA
      sensitized skin sites of MIF Tg mice, but were significantly decreased in MIF KO
      mice in comparison with the levels in WT littermates. Eotaxin expression was
      induced by IL-4 stimulation in fibroblasts in MIF Tg mice, but not in MIF KO
      mice. These findings indicate that MIF can induce eosinophil accumulation in the
      skin. Therefore, the targeted inhibition of MIF might be a promising new
      therapeutic strategy for allergic skin diseases.

PMID- 21191414
TI  - IL-4 and IL-13 alter plasmacytoid dendritic cell responsiveness to CpG DNA and
      herpes simplex virus-1.
AB  - Human plasmacytoid dendritic cells (pDCs) are found in skin lesions in a wide
      variety of diseases. The role of the microenvironment in these lesions on the
      function of human pDCs remains elusive. We sought to determine the effect of
      T(h)2 cytokines on the ability of human pDCs to respond to CpG
      oligodeoxynucleotides (ODNs) and herpes simplex virus in vitro. In this study, we
      found that the T(h)2 cytokines, IL-4 and IL-13, modulate Toll-like receptor 9
      (TLR-9)- and herpes simplex virus-induced pDC phenotype and enhance the ability
      of these cells to induce allogeneic T-cell responses. Moreover, T(h)2 cytokines
      impaired TLR-9-induced secretion of inflammatory cytokines and chemokines. Taken
      together, these results demonstrate that T(h)2 cytokines are involved in the
      modulation of pDC function and responsiveness to bacterial- and viral-derived
      stimuli.

PMID- 21191416
TI  - Expression of matrix metalloproteinase-13 is controlled by IL-13 via PI3K/Akt3
      and PKC-delta in normal human dermal fibroblasts.
AB  - IL-13, a T helper type 2 cytokine, is reported to be increased in the tissue of
      patients with atopic dermatitis (AD). In addition, chronic lichenified plaques in
      AD show thickened epidermis and dermis. We hypothesized that IL-13 is involved in
      tissue remodeling by altering the expression of matrix metalloproteinases (MMPs).
      In this study, we examined the MMP-related genes targeted by IL-13 in human
      dermal fibroblasts using a complementary DNA microarray. We focused on the MMP-13
      gene, which was identified as one of the MMPs suppressed by IL-13. IL-13
      downregulated both MMP-13 protein and mRNA expression. IL-13 suppressed MMP-13
      expression more effectively in the presence of protein kinase C (PKC)-delta
      inhibitor, whereas IL-13 upregulated MMP-13 in the presence of inhibitors of
      phosphoinositide 3-kinase (PI3K)/Akt pathway or Akt3-specific small interfering
      RNA. Our results suggest that MMP-13 expression is negatively controlled by
      PI3K/Akt3 and positively regulated by PKC-delta in the presence of IL-13. Taken
      together, these findings indicate that IL-13 may induce the formation of
      thickened dermis in AD by decreasing collagen degradation. Blockade of IL-13
      signaling cascades in AD patients may be a new therapeutic approach.

PMID- 21191415
TI  - IgE, IgM, and IgG4 anti-desmoglein 1 autoantibody profile in endemic pemphigus
      foliaceus (fogo selvagem).

PMID- 21191418
TI  - The Th2 systemic immune milieu enhances cutaneous inflammation in the K14-IL-4
      transgenic atopic dermatitis model.

PMID- 21191417
TI  - Delayed wound closure in fibromodulin-deficient mice is associated with increased
      TGF-beta3 signaling.
AB  - Fibromodulin (FMOD), a small leucine-rich proteoglycan, mediates scarless fetal
      skin wound repair through, in part, transforming growth factor-beta (TGF-beta)
      modulation. Using an adult fmod-null (fmod(-/-)) mouse model, this study further
      elucidates the interplay between FMOD and TGF-beta expression during cutaneous
      repair and scar formation. Full-thickness skin wounds on fmod(-/-) and wild-type
      (WT) mice were closed primarily and analyzed. Histomorphometry revealed delayed
      dermal cell migration leading to delayed wound closure and significantly
      increased scar size in fmod(-/-) mice relative to WT, which was partially rescued
      by exogenous FMOD administration. In addition, fmod(-/-) wounds exhibited early
      elevation (within 24  hours post-wounding) of type I and type II TGF-beta
      receptors as well as unexpectedly high fibroblast expression of TGF-beta3, a
      molecule with reported antifibrotic and antimigratory effects. Consistent with
      elevated fibroblastic TGF-beta3, fmod(-/-) fibroblasts were significantly less
      motile than WT fibroblasts. fmod(-/-) fibroblasts were also more susceptible to
      migration inhibition by TGF-beta3, leading to profound delays in dermal cell
      migration. Increased scarring in fmod(-/-) mice indicates that TGF-beta3's
      antimotility effects predominate over its antifibrotic effects when high TGF
      beta3 levels disrupt early fibroblastic wound ingress. These studies demonstrate
      that FMOD presence is critical for proper temporospatial coordination of wound
      healing events and normal TGF-beta bioactivity.

PMID- 21191419
TI  - Caspase-5 expression is upregulated in lesional psoriatic skin.
AB  - The inflammasome is a cytosolic multiprotein complex with two major functions:
      recognizing pathogen-associated molecular patterns and reacting to these through
      activation of the proinflammatory cytokines IL-1beta and IL-18. In this study, we
      characterized the expression of inflammasome components in psoriatic skin and
      other common inflammatory skin diseases. Human skin biopsy specimens, cultured
      primary human keratinocytes, and peripheral blood mononuclear cells (PBMCs) were
      analyzed using quantitative reverse transcriptase-PCR (RT-PCR) and
      semiquantitative western blotting. mRNA expression of the inflammasome components
      NALP1, NALP3, ASC, caspase-1, caspase-4, and caspase-5 was detected in psoriatic
      skin. Interestingly, we found an extensive, 20-fold upregulation (P<0.01) of
      caspase-5 mRNA in lesional compared with nonlesional psoriatic skin, whereas
      caspase-1, caspase-4, and ASC (apoptosis-associated speck-like protein with CARD
      domain) mRNAs were upregulated by only 1.5- to 2.6-fold (P<0.01). Caspase-5 mRNA
      was not increased in biopsies from other inflammatory skin diseases, suggesting
      that this finding could be psoriasis specific. In vitro experiments revealed that
      caspase-5 mRNA was induced in primary keratinocytes as well as PBMCs stimulated
      with IFN-gamma. Inhibition studies suggested that caspase-5 mRNA upregulation was
      mediated through the NF-kappaB pathway. Our findings suggest that caspase-5 and
      the inflammasome may have an important role in the inflammatory response in
      psoriasis.

PMID- 21191420
TI  - CD44 regulates tight-junction assembly and barrier function.
AB  - Upon barrier disturbance, adult CD44 knockout (KO) mice show delayed recovery of
      epidermal barrier function. This correlates with the loss of apical polarization
      of lamellar body (LB) secretion. As tight junctions (TJs) are crucial for barrier
      function and regulate polarized targeting of vesicles, we hypothesized that CD44
      regulates TJs and associated cell polarity complexes, which in turn contributes
      to altered skin barrier function in CD44 KO mice. We show a delay in embryonic
      barrier formation associated with a loss of apical LB localization in CD44 KO
      mice, which correlates with alterations in TJ proteins and Par3. Simultaneously,
      the activity of Rac1, a major regulator of TJ barrier function, was reduced.
      Importantly, normalization of barrier function at E18.5 coincided with the
      recovery of these proteins. Tape-stripping experiments revealed that the loss of
      CD44 also affected TJ proteins upon induced disturbance of the barrier in adult
      mice. In CD44 KO keratinocytes, cell polarization and TJ barrier function were
      impaired. An alteration of differentiation markers was also observed, but was
      less pronounced than alterations of TJ proteins. Taken together, the results
      reveal an important function for CD44 in the assembly and function of TJs,
      suggesting their involvement in the skin barrier phenotype of CD44 KO mice.

PMID- 21191421
TI  - Upregulation of aquaporin-3 is involved in keratinocyte proliferation and
      epidermal hyperplasia.
AB  - Aquaporin-3 (AQP3) is a water/glycerol-transporting protein expressed in
      keratinocytes of the epidermis. We previously showed that AQP3-mediated transport
      of water and glycerol is involved in keratinocyte migration and proliferation,
      respectively. However, the involvement of AQP3 in epidermal hyperplasia in skin
      diseases, such as atopic dermatitis (AD), is unknown. In this study, we found
      significantly increased AQP3 transcript and protein expression in the epidermis
      of human AD lesions. The upregulation of AQP3 expression in human keratinocytes
      by transfection with human AQP3 DNA plasmid was associated with increased
      cellular glycerol and ATP, as well as increased cell proliferation. Among several
      cytokines and chemokines produced in the skin, CCL17, which is highly expressed
      in AD, was found to be a strong inducer of AQP3 expression and enhanced
      keratinocyte proliferation. In mouse AD models, AQP3 was strongly overexpressed
      in the epidermis in wild-type mice. Epidermal hyperplasia was reduced in AQP3
      deficient mice, with a decreased number of proliferating keratinocytes. These
      results suggest the involvement of AQP3 in epidermal hyperplasia by a mechanism
      involving upregulated AQP3 expression and consequent enhancement of keratinocyte
      proliferation.

PMID- 21191422
TI  - Genomics: No half measures for haplotypes.

PMID- 21191424
TI  - Evolution: How networks get new layers.

PMID- 21191423
TI  - RNA sequencing: advances, challenges and opportunities.
AB  - In the few years since its initial application, massively parallel cDNA
      sequencing, or RNA-seq, has allowed many advances in the characterization and
      quantification of transcriptomes. Recently, several developments in RNA-seq
      methods have provided an even more complete characterization of RNA transcripts.
      These developments include improvements in transcription start site mapping,
      strand-specific measurements, gene fusion detection, small RNA characterization
      and detection of alternative splicing events. Ongoing developments promise
      further advances in the application of RNA-seq, particularly direct RNA
      sequencing and approaches that allow RNA quantification from very small amounts
      of cellular materials.

PMID- 21191425
TI  - Cardio classics revisited--focus on the role of candesartan.
AB  - Angiotensin II receptor blockers (ARBs) are antihypertensive agents with
      considerable evidence of efficacy and safety for the reduction of cardiovascular
      (CV) disease risk in numerous patient populations across the CV continuum. There
      are several agents within this class, all of which have contributed to various
      degrees, to this evidence base. The evidence with ARBs continues to accumulate,
      with ongoing trials investigating their role in additional patient populations,
      potentially expanding their efficacy across a broad spectrum of CV disease
      states. Cardiovascular disease (CVD) is a leading cause of death around the
      world, accounting for approximately 29.2% of total global deaths. Of all the
      deaths attributed to CVD, approximately 43% are due to ischemic heart disease,
      33% to cerebrovascular disease, and 23% to hypertensive and other heart
      conditions. CVD has been represented as a "CV continuum". This continuum concept
      can be used to describe CVD in general or in specific vascular beds (eg, coronary
      artery disease or cerebrovascular disease). This review article will discuss the
      results of the landmark ARB candesartan clinical trials published over the past
      decade. The evidence presented spans the entire CV continuum, including the
      effects of ARBs in at-risk patients, stroke, myocardial infarction (MI), and
      heart failure (HF), as well as a brief discussion of ongoing trials.

PMID- 21191426
TI  - Combination of niacin extended-release and simvastatin results in a less
      atherogenic lipid profile than atorvastatin monotherapy.
AB  - OBJECTIVE: To compare the effects of combination niacin extended-release +
      simvastatin (NER/S) versus atorvastatin alone on apolipoproteins and lipid
      fractions in a post hoc analysis from SUPREME, a study which compared the lipid
      effects of niacin extended-release + simvastatin and atorvastatin in patients
      with hyperlipidemia or mixed dyslipidemia. PATIENTS AND METHODS: Patients (n =
      137) with dyslipidemia (not previously receiving statin therapy or having
      discontinued any lipid-altering treatment 4-5 weeks prior to the study) received
      NER/S (1000/40 mg/day for four weeks, then 2000/40 mg/day for eight weeks) or
      atorvastatin 40 mg/day for 12 weeks. Median percent changes in apolipoprotein
      (apo) A-1, apo B, and the apo B:A-I ratio, and nuclear magnetic resonance
      lipoprotein subclasses from baseline to week 12 were compared using the Wilcoxon
      rank-sum test and Fisher's exact test. RESULTS: NER/S treatment produced
      significantly greater percent changes in apo A-I and apo B:A-I, and, at the final
      visit, apo B < 80 mg/dL was attained by 59% versus 33% of patients, compared with
      atorvastatin treatment (P = 0.003). NER/S treatment resulted in greater percent
      reductions in calculated particle numbers for low-density lipoprotein (LDL, 52%
      versus 43%; P = 0.022), small LDL (55% versus 45%; P = 0.011), very low-density
      lipoprotein (VLDL) and total chylomicrons (63% versus 39%; P < 0.001), and
      greater increases in particle size for LDL (2.7% versus 1.0%; P = 0.007) and VLDL
      (9.3% versus 0.1%; P < 0.001), compared with atorvastatin. CONCLUSION: NER/S
      treatment significantly improved apo A-I levels and the apo B:A-I ratio,
      significantly lowered the number of atherogenic LDL particles and VLDL and
      chylomicron particles, and increased the mean size of LDL and VLDL particles,
      compared with atorvastatin.

PMID- 21191427
TI  - Percutaneous coronary intervention of a single coronary artery arising from the
      right sinus of Valsalva.
AB  - Anomalous origin of the left main coronary artery from the right sinus of
      Valsalva is extremely rare when not associated with other congenital cardiac
      anomalies. In this report we present a patient with a single coronary ostium,
      with both the left and right coronary artery systems arising from it. The right
      coronary artery was found to contain a significant flow-limiting lesion that was
      successfully treated with percutaneous coronary intervention.

PMID- 21191428
TI  - Optimal management of familial hypercholesterolemia: treatment and management
      strategies.
AB  - Familial hypercholesterolemia is an autosomally dominant disorder caused by
      various mutations in low-density lipoprotein receptor genes. This will lead to
      elevated levels of total and low-density lipoprotein cholesterol, which may in
      turn lead to premature coronary atherosclerosis and cardiac-related death. The
      symptoms are more severe in the homozygous type of the disease. Different options
      for the treatment of affected patients are now available. Diet therapy,
      pharmacologic therapy, lipid apheresis, and liver transplantation are among the
      various treatments. We clinically review the treatment and management strategies
      for the disease in order to shed light on the optimal management of familial
      hypercholesterolemia.

PMID- 21191430
TI  - Lower extremity arterial injuries over a six-year period: outcomes, risk factors,
      and management.
AB  - PURPOSE: Limb loss following lower extremity arterial injury is not uncommon and
      has serious implications on the patient's life and functionality. This
      retrospective study was performed to analyze the results of lower extremity
      arterial injuries and to identify the risk factors associated with amputation.
      METHODS: Between 2002 and 2009, retrospectively collected data on 140 patients
      with 173 lower extremity arterial injuries were analyzed. RESULTS: There were 133
      males (95%) and 7 females (5%). The mechanism of injuries was gunshot wounds in
      56.4% of cases, stab wounds in 30%, and blunt trauma in 13.4%. Associated
      injuries included vein injury in 45% of cases, nerve injury in 16.4%, and bone
      fracture in 31.4%. The most frequently injured artery was superficial femoral
      artery (31.2%). More than 1 artery was injured in 18.6% of patients. Surgery was
      carried out, with a limb salvage rate of 90.4% and a survival of 97.1%.
      Amputation was performed in 75% of patients in whom only 1 artery was repaired,
      although all crural arteries were injured. Multivariate logistic regression
      analysis showed that significant risk factors of outcome were below-knee multiple
      arterial injuries (odds ratio [OR] 6.62, P < 0.001), associated 2-bone fractures
      (OR 2.71, P = 0.003), development of compartment syndrome (OR 1.94, P = 0.042),
      and great soft tissue disruption (OR 1.74, P = 0.010). CONCLUSIONS: Limb loss may
      be decreased by performing prophylactic fasciotomy more often and by repairing at
      least 2 crural arteries.

PMID- 21191429
TI  - Insulin therapy in critically ill patients.
AB  - Hyperglycemia frequently occurs with acute medical illness, especially among
      patients with cardiovascular disease, and has been linked to increased morbidity
      and mortality in critically ill patients. Even patients who are normoglycemic can
      develop hyperglycemia in response to acute metabolic stress. An expanding body of
      literature describes the benefits of normalizing hyperglycemia with insulin
      therapy in hospitalized patients. As a result, both the American Diabetes
      Association and the American College of Endocrinology have developed guidelines
      for optimal control of hyperglycemia, specifically targeting critically ill,
      hospitalized patients. Conventional blood glucose values of 140-180 mg/dL are
      considered desirable and safely achievable in most patients. More aggressive
      control to <110 mg/dL remains controversial, but has shown benefits in certain
      patients, such as those in surgical intensive care. Intravenous infusion is often
      used for initial insulin administration, which can then be transitioned to
      subcutaneous insulin therapy in those patients who require continued insulin
      maintenance. This article reviews the data establishing the link between
      hyperglycemia and its risks of morbidity and mortality, and describes strategies
      that have proven effective in maintaining glycemic control in high-risk
      hospitalized patients.

PMID- 21191431
TI  - Stent-grafts in the management of life-threatening hemorrhage following
      inadvertent femoral catheterization in high-risk patients: report of two cases
      and review of the literature.
AB  - Bleeding related to inadvertent femoral catheter insertion is an infrequent but
      morbid complication. We report two cases of acute life-threatening bleeding after
      attempts at femoral vein catheterization. Both patients were morbidly obese, had
      multiple comorbidities, and were at high risk for surgical intervention.
      Aggressive resuscitation failed to stabilize the patients. Emergency digital
      subtraction angiography diagnosed the site of the femoral artery bleeding. In one
      patient, the site of injury was the right profunda femoris artery. Both bleeding
      sites were controlled successfully with endovascular covered stent placement,
      without complication. Although prior publications have reported the concept of
      endovascular repair in femoral artery injuries, to the best of the author's
      knowledge, covering the profunda femoris artery with no complications has not
      been described previously. In critically ill patients with life-threatening
      hemorrhage following inadvertent femoral catheterization, management with
      endovascular covered stents is safe and effective.

PMID- 21191432
TI  - Inhaled treprostinil and pulmonary arterial hypertension.
AB  - Multiple conditions result in development of pulmonary hypertension. Pulmonary
      arterial hypertension (PAH) is the subclassification of pulmonary hypertension,
      in which known or unknown underlying conditions lead to similar intrinsic
      alterations in the pulmonary vasculature. PAH is a progressive condition
      characterized by restricted blood flow through the pulmonary circulation leading
      to poor survival in the absence of effective therapy. Over the last two decades,
      new therapeutic agents have substantially improved the course and prognosis for
      PAH patients. Three available classes of drugs, ie, prostacyclins, endothelin
      receptor antagonists, and phosphodiesterase-5 inhibitors provide multiple options
      for treatment of PAH. Endothelin receptor antagonists and phosphodiesterase-5
      inhibitors are administered orally, whereas prostacyclin therapies are delivered
      by continuous intravenous or subcutaneous infusion, or as aerosols by
      nebulization. Because of the risks and inconveniences associated with
      administration, prostacyclins are typically reserved for patients with more
      advanced disease or progression despite oral therapy. Inhaled administration may
      be a safer and easier route for prostacyclin administration. Treprostinil is a
      prostacyclin analog that has been demonstrated to be effective when administered
      by continuous subcutaneous or intravenous infusion, and more recently by
      nebulization.

PMID- 21191433
TI  - Detection of circulating microparticles by flow cytometry: influence of
      centrifugation, filtration of buffer, and freezing.
AB  - The clinical importance of microparticles resulting from vesiculation of
      platelets and other blood cells is increasingly recognized, although no
      standardized method exists for their measurement. Only a few studies have
      examined the analytical and preanalytical steps and variables affecting
      microparticle detection. We focused our analysis on microparticle detection by
      flow cytometry. The goal of our study was to analyze the effects of different
      centrifugation protocols looking at different durations of high and low
      centrifugation speeds. We also analyzed the effect of filtration of buffer and
      long-term freezing on microparticle quantification, as well as the role of
      Annexin V in the detection of microparticles. Absolute and platelet-derived
      microparticles were 10- to 15-fold higher using initial lower centrifugation
      speeds at 1500 * g compared with protocols using centrifugation speeds at 5000 *
      g (P < 0.01). A clear separation between true events and background noise was
      only achieved using higher centrifugation speeds. Filtration of buffer with a 0.2
      MUm filter reduced a significant amount of background noise. Storing samples for
      microparticle detection at -80 degrees C decreased microparticle levels at days
      28, 42, and 56 (P < 0.05 for all comparisons with fresh samples). We believe that
      staining with Annexin V is necessary to distinguish true events from cell debris
      or precipitates. Buffers should be filtered and fresh samples should be analyzed,
      or storage periods will have to be standardized. Higher centrifugation speeds
      should be used to minimize contamination by smaller size platelets.

PMID- 21191434
TI  - Improving adherence with inhaler therapy in COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is a major public health problem,
      associated with considerable morbidity and health care costs. The global burden
      of COPD morbidity is predicted to rise substantially in the coming decade, but
      could be moderated by better use of existing management strategies. Smoking
      cessation, medication therapy, and pulmonary rehabilitation have all been shown
      to diminish morbidity and improve patient outcomes. But each of these strategies
      requires adherence. Adherence is crucial for optimizing clinical outcomes in
      COPD, with nonadherence resulting in a significant health and economic burden.
      Suboptimal medication adherence is common among COPD patients, due to a number of
      factors that involve the medication, the delivery device, the patient, and the
      health professionals caring for the patient. Lack of medication adherence needs
      to be identified and addressed by using simplified treatment regimens, increasing
      patient knowledge about self-management, and enhancing provider skills in patient
      education, communication, and adherence counseling. This article reports some of
      the challenges of medication nonadherence faced by the clinician in the
      management of COPD, and suggests ways to evaluate and improve adherence
      effectively in primary care.

PMID- 21191436
TI  - In search of parsimony: reliability and validity of the Functional Performance
      Inventory-Short Form.
AB  - PURPOSE: the 65-item Functional Performance Inventory (FPI), developed to
      quantify functional performance in patients with chronic obstructive pulmonary
      disease (COPD), has been shown to be reliable and valid. The purpose of this
      study was to create a shorter version of the FPI while preserving the integrity
      and psychometric properties of the original. PATIENTS AND METHODS: secondary
      analyses were performed on qualitative and quantitative data used to develop and
      validate the FPI long form. Seventeen men and women with COPD participated in the
      qualitative work, while 154 took part in the mail survey; 54 completed 2-week
      reproducibility assessment, and 40 relatives contributed validation data.
      Following a systematic process of item reduction, performance properties of the
      32-item short form (FPI-SF) were examined. RESULTS: the FPI-SF was internally
      consistent (total scale alpha = 0.93; subscales: 0.76-0.89) and reproducible (r =
      0.88; subscales: 0.69-0.86). Validity was maintained, with significant (P <
      0.001) correlations between the FPI-SF and the Functional Status Questionnaire
      (activities of daily living, r = 0.71; instrumental activities of daily living, r
      = 0.73), Duke Activity Status Index (r = 0.65), Bronchitis-Emphysema Symptom
      Checklist (r = -0.61), Basic Need Satisfaction Inventory (r = 0.61) and Cantril's
      Ladder of Life Satisfaction (r = 0.63), and Katz Adjustment Scale for Relatives
      (socially expected activities, r = 0.51; free-time activities, r = -0.49, P <
      0.01). The FPI-SF differentiated patients with an FEV(l)% predicted greater than
      and less than 50% (t = 4.26, P < 0.001), and those with severe and moderate
      levels of perceived severity and activity limitation (t = 9.91, P < 0.001).
      CONCLUSION: results suggest the FPI-SF is a viable alternative to the FPI for
      situations in which a shorter instrument is desired. Further assessment of the
      instrument's performance properties in new samples of patients with COPD is
      warranted.

PMID- 21191435
TI  - Sustained effects of integrated COPD management on health status and exercise
      capacity in primary care patients.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) constitutes a growing
      health care problem worldwide. Integrated disease management (IDM) of mild to
      moderate COPD patients has been demonstrated to improve exercise capacity and
      health status after one year, but long-term results are currently lacking in
      primary care. METHODS: Long-term data from the Bocholtz study, a controlled
      clinical trial comparing the effects of IDM versus usual care on health status in
      106 primary care COPD patients during 24 months of follow-up, were analyzed using
      the Clinical COPD Questionnaire (CCQ). In addition, the Kroonluchter IDM
      implementation program has treated 216 primary care patients with mild to
      moderate COPD since 2006. Longitudinal six-minute walking distance (6MWD) results
      for patients reaching 24 months of follow-up were analyzed using paired-sample t
      tests. In prespecified subgroup analyses, the differential effects of baseline
      CCQ score, Medical Research Council (MRC) dyspnea score, and 6MWD were
      investigated. RESULTS: In the Bocholtz study, subjects were of mean age 64 years,
      with an average postbronchodilator forced expiratory volume in one second
      (FEV(1)) of 63% predicted and an FEV(1)/forced vital capacity (FVC) ratio of
      0.56. No significant differences existed between groups at baseline. CCQ improved
      significantly and in a clinically relevant manner by 0.4 points over 24 months;
      effect sizes were doubled in patients with CCQ > 1 at baseline and tripled in
      patients with MRC dyspnea score >2. In the Kroonluchter cohort, 56 subjects
      completed follow-up, were of mean age 69 years, with an FEV(1)/FVC ratio of 0.59,
      while their postbronchodilator FEV(1) of 65% predicted was somewhat lower than in
      the total group. 6MWD improved significantly and in a clinically relevant manner
      up to 93 m at 12 months and was sustained at 83 m over 24 months; this effect
      occurred faster in patients with MRC dyspnea score >2. In patients with baseline
      6MWD < 400 m the improvement remained >100 m at 24 months. CONCLUSION: In this
      study, IDM improved and sustained health status and exercise capacity in primary
      care COPD patients during two years of follow-up. Improvements in health status
      are consistently higher in patients with CCQ > 1 at baseline, being strongest in
      patients with baseline MRC dyspnea score >2. Improvements in exercise capacity
      remain highest in patients with 6MWD < 400 m at baseline and seem to occur
      earlier in patients with MRC dyspnea score >2.

PMID- 21191437
TI  - Validation of alternate modes of administration of the lung function
      questionnaire (LFQ) in subjects with smoking history.
AB  - PURPOSE: The lung Function Questionnaire (LFQ) was developed and validated as a
      case-finding tool to identify patients at risk of airflow obstruction (AO) that
      should be evaluated further using spirometry. Our objective was to assess the
      usability and validity of additional questionnaire-administration modes,
      including Web-based, interactive voice response system (IVRS)-based, and
      interviewer-based modes. DESIGN: This multicenter, prospective, noninterventional
      data-collection study enrolled 149 individuals aged >=40 years with current or
      former smoking history. A two-visit crossover design was employed; patients
      completed the paper-based LFQ and were randomly assigned to complete one of three
      alternate modes. METHODS: Statistical evaluation included item-level, scale
      level, and AO risk-classification comparisons; a satisfaction survey assessed
      patient preference. RESULTS: this study showed a great degree of concordance
      between alternate forms of the LFQ and the paper version. Results indicated an
      absence of floor and ceiling effects and the average LFQ item-level means were
      consistent across modes. LFQ scores were stable between assessments,
      (administered approximately one week apart) showed exceptionally good agreement,
      and AO risk classification using the LFQ cut point was consistent across modes.
      CONCLUSIONS: The LFQ is an important case-finding tool to aid primary care
      physicians in further evaluating symptomatic patients at risk of AO. The
      alternate modes will further facilitate the implementation and widespread uptake
      of this tool.

PMID- 21191438
TI  - Association between lung function and exacerbation frequency in patients with
      COPD.
AB  - PURPOSE: To quantify the relationship between severity of chronic obstructive
      pulmonary disease (COPD) as expressed by Global Initiative for Chronic
      Obstructive Lung Disease (GOLD) stage and the annual exacerbation frequency in
      patients with COPD. METHODS: We performed a systematic literature review to
      identify randomized controlled trials and cohort studies reporting the
      exacerbation frequency in COPD patients receiving usual care or placebo. Annual
      frequencies were determined for total exacerbations defined by an increased use
      of health care (event-based), total exacerbations defined by an increase of
      symptoms, and severe exacerbations defined by a hospitalization. The association
      between the mean forced expiratory volume in one second (FEV(1))% predicted of
      study populations and the exacerbation frequencies was estimated using weighted
      log linear regression with random effects. The regression equations were applied
      to the mean FEV(1)% predicted for each GOLD stage to estimate the frequency per
      stage. RESULTS: Thirty-seven relevant studies were found, with 43 reports of
      total exacerbation frequency (event-based, n = 19; symptom-based, n = 24) and 14
      reports of frequency of severe exacerbations. Annual event-based exacerbation
      frequencies per GOLD stage were estimated at 0.82 (95% confidence interval 0.46
      1.49) for mild, 1.17 (0.93-1.50) for moderate, 1.61 (1.51-1.74) for severe, and
      2.10 (1.51-2.94) for very severe COPD. Annual symptom-based frequencies were 1.15
      (95% confidence interval 0.67-2.07), 1.44 (1.14-1.87), 1.76 (1.70-1.88), and 2.09
      (1.57-2.82), respectively. For severe exacerbations, annual frequencies were 0.11
      (95% confidence interval 0.02-0.56), 0.16 (0.07-0.33), 0.22 (0.20-0.23), and 0.28
      (0.14-0.63), respectively. Study duration or type of study (cohort versus trial)
      did not significantly affect the outcomes. CONCLUSION: This study provides an
      estimate of the exacerbation frequency per GOLD stage, which can be used for
      health economic and modeling purposes.

PMID- 21191439
TI  - Emotion causes targeted forgetting of established memories.
AB  - Reconsolidation postulates that reactivation of a memory trace renders it
      susceptible to disruption by treatments similar to those that impair initial
      memory consolidation. Despite evidence that implicit, or non-declarative, human
      memories can be disrupted at retrieval, a convincing demonstration of selective
      impairment in retrieval of target episodic memories following reactivation is
      lacking. In human subjects, we demonstrate that if reactivation of a verbal
      memory, through successful retrieval, is immediately followed by an emotionally
      aversive stimulus, a significant impairment is evident in its later recall. This
      effect is time-dependent and persists for at least 6 days. Thus, in line with a
      reconsolidation hypothesis, established human episodic memories can be
      selectively impaired following their retrieval.

PMID- 21191440
TI  - Non-heat related impacts of climate change on working populations.
AB  - Environmental and social changes associated with climate change are likely to
      have impacts on the well-being, health, and productivity of many working
      populations across the globe. The ramifications of climate change for working
      populations are not restricted to increases in heat exposure. Other significant
      risks to worker health (including physical hazards from extreme weather events,
      infectious diseases, under-nutrition, and mental stresses) may be amplified by
      future climate change, and these may have substantial impacts at all scales of
      economic activity. Some of these risks are difficult to quantify, but pose a
      substantial threat to the viability and sustainability of some working
      populations. These impacts may occur in both developed and developing countries,
      although the latter category is likely to bear the heaviest burden.This paper
      explores some of the likely, non-heat-related health issues that climate change
      will have on working populations around the globe, now and in the future. These
      include exposures to various infectious diseases (vector-borne, zoonotic, and
      person-to-person), extreme weather events, stress and mental health issues, and
      malnutrition.

PMID- 21191441
TI  - Diurnal IOP-lowering efficacy and safety of travoprost 0.004% compared with
      tafluprost 0.0015% in patients with primary open-angle glaucoma or ocular
      hypertension.
AB  - PURPOSE: To compare the diurnal intraocular pressure (IOP)-lowering efficacy and
      safety of travoprost 0.004% and tafluprost 0.0015% administered to patients with
      primary open-angle glaucoma or ocular hypertension. METHODS: This was a
      randomized, double-masked, active-controlled, crossover design trial, in which
      patients were randomized to either travoprost or tafluprost monotherapy
      administered once daily in the evening for six weeks and then crossed over to the
      alternative treatment for another six weeks. Diurnal IOP was measured (8 am to 8
      pm, every two hours) and a solicited symptom survey was administered at the end
      of both six-week periods, as was conjunctival hyperemia and visual acuity
      assessment, slit-lamp biomicroscopy, and adverse event solicitation. RESULTS:
      Fifty-one patients were randomized and 48 patients completed the study. The 12
      hour mean diurnal IOP was significantly lower with travoprost therapy than with
      tafluprost therapy (P = 0.01), and a significantly lower IOP was also reported
      for travoprost at five of the seven individual time points (P < 0.05). Neither
      therapy produced a significant increase from baseline in any of the individual
      patient-reported symptom scores, except for hyperemia (P <= 0.01), which was
      increased with both treatments. Investigator-observed hyperemia was also
      increased from baseline with both therapies (P < 0.01), although the increase
      with travoprost therapy was significantly smaller than with tafluprost (P <
      0.01). No additional safety concerns were noted from slit-lamp biomicroscopy or
      visual acuity results, and no difference was noted in patient-reported
      tolerability of the two medications. CONCLUSION: Travoprost 0.004% monotherapy
      produced lower diurnal IOP than tafluprost 0.0015% in patients with primary open
      angle glaucoma or ocular hypertension and exhibited a similar safety profile.

PMID- 21191442
TI  - Contralateral comparison of blue-filtering and non-blue-filtering intraocular
      lenses: glare disability, heterochromatic contrast, and photostress recovery.
AB  - PURPOSE: To compare visual performance in eyes with intraocular lenses (IOLs)
      that filter short-wave blue light versus contralateral eyes with IOLs that do not
      filter visible blue light. METHODS: In this prospective, assessor-masked study
      that was conducted at five clinics in the US, eligible candidates were at least
      12 months postimplantation of a control IOL and a contralateral IOL that filtered
      blue light. Glare disability was defined as the intensity of a white-light
      annulus that obscured a subject's ability to see a central target.
      Heterochromatic contrast thresholds were defined as the intensity of a blue-light
      disk that obscured a central target. Photostress recovery time was the duration
      required to regain sight of the target after a five-second flash of annulus
      light. RESULTS: Fifty-two subjects were evaluated. Mean glare disability was
      significantly less (P = 0.04) in the blue-filtering IOL group (1.97 +/- 0.44 log
      MUW/cm(2)) than in the control group (1.88 +/- 0.43 log MUW/cm(2)). Mean
      heterochromatic contrast threshold was significantly higher (P = 0.0003) in the
      blue-filtering IOL group (0.36 +/- 0.43 log MUW/cm(2)) than in the control IOL
      group (0.15 +/- 0.49 log MUW/cm(2)). Geometric mean photostress recovery time was
      significantly faster (P = 0.02) in the blue-filtering IOL group (21 +/- 3
      seconds) than in the control IOL group (26 +/- 3 seconds). CONCLUSIONS: Glare
      disability was significantly lower, heterochromatic contrast threshold was
      significantly better, and recovery from photostress was significantly faster in
      the eyes with blue-filtering IOLs than in the contralateral control eyes with
      IOLs that did not filter blue light.

PMID- 21191443
TI  - Viscogonioplasty in narrow angle glaucoma: a randomized controlled trial.
AB  - PURPOSE: To determine the effect of viscogonioplasty and cataract extraction on
      intraocular pressure in patients with narrow angle glaucoma. METHODS: This was a
      double-masked randomized controlled trial involving 50 eyes (25 cases and 25
      controls) from 38 consecutive patients. All patients underwent
      phacoemulsification with or without viscogonioplasty. The main outcome measures
      were intraocular pressure post-treatment and number of glaucoma medications post
      treatment. RESULTS: Cases had a greater reduction in intraocular pressure than
      controls, with a mean intraocular pressure (standard deviation) at 12 months of
      13.7 (+/-2.89) mmHg compared with 16.2 (+/-3.55) mmHg in controls (P = 0.009).
      Cases had a greater reduction in mean number of antiglaucoma medications than
      controls at 12-month review, with 13 of 25 eyes (52%) of cases controlled without
      any antiglaucoma therapy versus 9 of 25 (36%) of the controls (P = 0.005).
      CONCLUSIONS: Viscogonioplasty combined with cataract extraction has a
      significantly greater effect than cataract extraction alone on lowering
      intraocular pressure in patients with poorly controlled narrow angle glaucoma and
      should therefore be considered as a treatment option for patients with this
      condition.

PMID- 21191444
TI  - Prospective comparison of two methods of screening for diabetic retinopathy by
      nonmydriatic fundus camera.
AB  - PURPOSE: To compare the results obtained by two screening techniques for diabetic
      retinopathy. METHODS: Patients were assessed in two groups, according to whether
      the retinal images were analyzed by the general practitioner (Group 1) or by the
      ophthalmologist (Group 2) in a two-year prospective study using telemedicine.
      RESULTS: The number of patients referred to the nonmydriatic fundus camera unit
      was higher in Group 1 than in Group 2 (63.80% versus 17.63%). Greater patient
      adherence was observed in Group 1 than in Group 2 when patients came to
      retinography (98.25% versus 87.52%). There were no significant differences in
      other technique variables. The prevalence of diabetic retinopathy was similar in
      both groups (8.98% in Group 1 and 9.16% in Group 2), but the prevalence of severe
      proliferative diabetic retinopathy was higher in Group 2 (1.69% [severe] and
      0.45% [proliferative]) than in Group 1 (1.01% and 0.11%, respectively). Diabetic
      macular edema was more prevalent in Group 2 (2.03%). CONCLUSIONS: The inclusion
      of general practitioners in the screening method seems to be important. A great
      number of patients with diabetes mellitus were screened, and a higher percentage
      of patients with diabetic retinopathy or macular edema were detected.

PMID- 21191445
TI  - Identification of noncompliant glaucoma patients using Bayesian networks and the
      Eye-Drop Satisfaction Questionnaire.
AB  - OBJECTIVE: To identify poorly compliant glaucoma patients, using the Eye-Drop
      Satisfaction Questionnaire (EDSQ). METHODS: This was an observational cross
      sectional study with compliance data collected by an electronic monitoring
      device. Patients with primary open-angle glaucoma or ocular hypertension
      completed the EDSQ, a six-dimension self-reported questionnaire addressing
      "treatment concern", "disease concern", "patient-clinician relationship",
      "positive beliefs", "treatment convenience", and "self-declared compliance". A
      Bayesian network (BN) was applied to explore compliance associations with EDSQ.
      RESULTS: Among 169 patients who completed the EDSQ, 113 had valid Travalert(r)
      data, of whom 25 (22.1%) demonstrated low compliance. All six EDSQ dimensions
      were associated directly, or indirectly, with compliance. Two profiles exhibited
      low compliance, ie, patients aged younger than 77.5 years with a poor patient
      physician relationship and self-declared poor compliance and patients aged older
      than 77.5 years with a poor patient-physician relationship and self-declared good
      compliance. The third profile showed high compliance, ie, patients aged younger
      than 77.5 years with a good patient-physician relationship and self-declared good
      compliance. CONCLUSION: Our results confirm a central role for the patient
      physician relationship in the compliance process. Age, self-declared compliance,
      and patient satisfaction with the patient-physician relationship are all
      dimensions worth exploring before glaucoma medication is switched or proceeding
      to laser treatment or surgery.

PMID- 21191446
TI  - Autofluorescence imaging - a useful adjunct in imaging macular trauma.
AB  - Autofluorescence imaging is a rapid, noninvasive technique, with several
      applications becoming slowly integrated into ophthalmic clinical practice. We
      describe its use as a valuable tool for predicting the function of the retinal
      pigment epithelium following damage from blunt ocular trauma.

PMID- 21191447
TI  - Randomized controlled trial on the safety of intracameral cephalosporins in
      cataract surgery.
AB  - OBJECTIVE: To compare the safety profiles of intracameral cephalosporins in
      cataract surgery. PATIENTS AND METHODS: In this controlled trial, 129 patients
      were randomized to one of four groups to receive 1 mg of one of three
      cephalosporins - cefazolin, cefuroxime, or ceftazidime, or normal saline - given
      intracamerally during cataract surgery. Central endothelial cell density (ECD)
      and retinal center point thickness (CPT) were determined by specular microscopy
      and ocular coherence tomography, respectively, before and at 3 months after
      surgery. RESULTS: There were no statistical significant differences in the
      changes of ECD and CPT between eyes receiving intracameral cephalosporin and
      control. CONCLUSION: The use of intracameral cefazolin, cefuroxime, or
      ceftazidime (1 mg in 0.1-mL solution) at the time of cataract surgery had no
      significant effect on ECD and CPT postoperatively.

PMID- 21191450
TI  - Erratum: corrigendum.
AB  - [This corrects the article on p. 1391 in vol. 4, PMID: 21179224.].

PMID- 21191448
TI  - Methicillin resistance of Staphylococcus species among health care and nonhealth
      care workers undergoing cataract surgery.
AB  - PURPOSE: The purpose of this study is to characterize the bacterial flora of the
      ocular and periocular surface in cataract surgery patients and to determine the
      prevalence of methicillin resistance among staphylococcal isolates obtained from
      health care workers (HCWs) and non-HCWs. METHODS: In this prospective,
      multicenter, case series study, eyelid and conjunctival cultures were obtained
      from the nonoperative eye of 399 consecutive cataract patients on the day of
      surgery prior to application of topical anesthetics, antibiotics, or antiseptics.
      Speciation and susceptibility testing were performed at the Dean A. McGee Eye
      Institute. Logistic regression was utilized to evaluate whether any factors were
      significant in predicting the presence of methicillin-resistant staphylococcal
      isolates. RESULTS: Staphylococcus epidermidis (62.9%), followed by S. aureus
      (14.0%), was the most frequently isolated organism. Methicillin-resistant S.
      epidermidis accounted for 47.1% (178/378) of S. epidermidis isolates, and
      methicillin-resistant S. aureus accounted for 29.5% (26/88) of S. aureus
      isolates. Methicillin-resistant staphylococcal isolates were found in 157 of 399
      (39.3%) patients, the majority (89.2%) of whom were non-HCWs. The likelihood of
      being colonized with methicillin-resistant organisms increased with age (odds
      ratio [OR], 1.27; 95% confidence interval [CI]: 1.02-1.58; P = 0.04) but
      decreased with diabetes (OR, 0.51; 95% CI: 0.29-0.89; P = 0.02). Being a HCW (OR,
      1.25; 95% CI: 0.61-2.58; P = 0.54) was not a risk factor for colonization with
      methicillin-resistant organisms. CONCLUSION: Patients without exposure to health
      care environments are as likely as HCWs to be colonized with methicillin
      resistant organisms. Increasing methicillin resistance with age may partially
      explain the increased risk of endophthalmitis reported with older age.

PMID- 21191449
TI  - Pattern-reversal visual-evoked potential in patients with occult macular
      dystrophy.
AB  - PURPOSE: Occult macular dystrophy (OMD) is a hereditary retinal disease
      characterized by a normal fundus, normal full-field electroretinograms (ERGs),
      progressive decrease of visual acuity, and abnormal focal macular ERGs. The
      purpose of this study was to report pattern-reversal visual-evoked potential
      (pVEPs) findings in OMD patients. PATIENTS AND METHOD: The pVEPs recorded from
      four patients with OMD (aged 42-61 years; 2 men and 2 women) were reviewed. The
      visual acuities ranged from 20/200 to 20/30. The amplitudes of the N-75 and P-100
      (P2 amplitude) and the latency of the N-75 components (N1 latency) were analyzed.
      RESULTS: The mean (+/-SD) P2 amplitude was 2.7 +/- 1.9 MUV for the 5', 4.8 +/-
      2.9 MUV for the 10', 3.2 +/- 2.1 MUV for the 20', and 4.4 +/- 3.5 MUV for the 40'
      checkerboard stimuli. The N1 latency was 122.2 +/- 6.4 ms for the 5', 105.0 +/-
      11.5 ms for the 10', 97.7 +/- 10.0 ms for the 20', and 91.0 +/- 13.7 ms for the
      40' checkerboard stimuli. The mean P2 amplitude was reduced and the N1 latency
      was delayed in comparison with the laboratory standard for the Keio University
      Hospital. CONCLUSIONS: The delayed latency and reduced amplitude suggest a major
      contribution of the central cone pathway to the pVEPs.

PMID- 21191451
TI  - Evidence Based Family Wellness Interventions, Still Not HIV Prevention: Reply to
      Collins.

PMID- 21191452
TI  - Doing more with less: Teacher professional learning communities in resource
      constrained primary schools in rural China.
AB  - Teacher professional learning communities provide environments in which teachers
      engage in regular research and collaboration. They have been found effective as a
      means for connecting professional learning to the day-to-day realities faced by
      teachers in the classroom. In this paper, we draw on survey data collected in
      primary schools serving 71 villages in rural Gansu Province, as well as
      transcripts from in-depth interviews with 30 teachers. Our findings indicate that
      professional learning communities penetrate to some of China's most resource
      constrained schools, but that their nature and development are shaped by
      institutional supports, principal leadership, and teachers' own initiative.

PMID- 21191453
TI  - Poverty, Parental Ill Health and Children's Access to Schooling in Rural Gansu,
      China.

PMID- 21191454
TI  - Green tea consumption and stomach cancer risk: a meta-analysis.
AB  - OBJECTIVES: Green tea has been suggested to have a chemopreventive effect against
      various cancers including stomach cancer. The aim of this study is to elucidate
      the relationship between green tea consumption and stomach cancer risk by meta
      analysis. METHODS: Eighteen observational studies were identified using MEDLINE,
      THE COCHRANE LIBRARY, RISS, and a manual search. Summary relative risks/odds
      ratios (RR/ORs) for the highest versus non/lowest green tea consumption levels
      were calculated on the basis of fixed and random effect models. Subgroup analyses
      were used to examine heterogeneity across the studies. RESULTS: The combined
      results indicate a reduced risk of stomach cancer with intake of green tea
      (RR/OR=0.86, 95% CI=0.74-1.00). Subgroup analysis with six studies that reported
      differences between the highest and lowest consumption levels equal to or greater
      than five cups/day revealed a statistically significant protective effect
      (RR/OR=0.68, 95% CI=0.53-0.87). CONCLUSION: Green tea appears to play a
      protective role against the development of stomach cancer. The results also
      suggest that a higher level of green tea consumption might be needed for a clear
      preventive effect to appear. This conclusion, however, should be interpreted with
      caution because various biases can affect the results of a meta-analysis.

PMID- 21191455
TI  - A fatal case of disseminated tuberculosis coincident with measles-rubella
      vaccination.
AB  - The authors report a fatal case of disseminated tuberculosis in a 14-yr-old girl,
      which developed immediately after a measles-rubella (MR) vaccination. Despite a
      markedly accelerated clinical course which led to death within two weeks, the
      authors could not identify any possible cause of the tuberculosis aggravation in
      this case, with the exception of the MR vaccination. The possible role that MR
      vaccination had on the clinical course of tuberculosis in this case is discussed.

PMID- 21191457
TI  - Relations of pulse wave velocity to waist circumference independent of hip
      circumference.
AB  - OBJECTIVES: Little is known about the effect of waist circumference (WC) on
      brachial artery pulse wave velocity (baPWV) independent of hip circumference
      (HC). Therefore, this study aimed to dissociate specific effect of WC on baPWV
      independent of HC. METHODS: Of 1,053 rural residents (2004-2005), 777 subjects
      with no known history of coronary artery diseases or diabetes mellitus over 40 yr
      were included. To reduce collinearity, we assessed the independent effect of WC
      with HC on PWV by residual method (WC [RM]). RESULTS: In women, most correlation
      coefficients were significant between measures of abdominal obesity and baPWV,
      with the highest (0.32) in waist to hip ratio (WHR), whereas no significance was
      found in men. All mean values of baPWV among the abdominally obese were higher
      than those of normal group in women, which were in the order of WHR, WC (RM), and
      WC. Adjusted OR with 95% CI for baPWV was significantly elevated by increase of
      WC (RM) upto 4.8 (95% CI: 2.1-11.2), and as 4.3 by WHR (95% CI: 1.6-11.4).
      CONCLUSION: Considering the difficulty in biologically interpreting WHR, WC (RM)
      may be a useful indicator of abdominal obesity among females in that it reflects
      the risk of pulse wave velocity.

PMID- 21191458
TI  - Comparison of prevalence of metabolic syndrome between korean emigrants and host
      country residents in Japan and china-the korean emigrant study.
AB  - OBJECTIVES: This study aims to compare the prevalence of metabolic syndrome
      between Korean emigrants (KEs) and their host country residents in Japan and
      China. METHODS: The Korean Emigrant Study (KES) is a cohort study initiated in
      2005 to elucidate the effect of genetic susceptibility and environmental change
      on hypertension, diabetes, and metabolic syndrome. Equal numbers of KEs and host
      country residents, aged 30 or over, were recruited from three regions; Kobe-Osaka
      in Japan (total number=965), Yanbian in China (n=1,019), and Changchun in China
      (n=949). RESULTS: The age-adjusted prevalences of metabolic syndrome among KEs in
      Kobe-Osaka were significantly higher than those among Japanese (in men 24.0% vs.
      15.6%, p=0.04, in women 8.4% vs. 2.7%, p=0.01), while the age-adjusted
      prevalences among KEs in Changchun were similar to those among Chinese (in men
      11.7% vs. 16.1%, p=0.37, in women 28.3% vs. 30.1%, p=0.91). The age-adjusted
      prevalences were generally higher in Yanbian than other regions, and KEs had
      higher prevalence than Chinese in men but not in women (in men 37.9% vs. 28.3%,
      p=0.03, women 46.0% vs. 50.6%, p=0.44). The components with significant ethnic
      differences in prevalence were high blood pressure and abdominal obesity in
      Japan, and triglyceride in China. The most influential component in diagnosing
      metabolic syndrome was abdominal obesity in men and triglyceride in women.
      CONCLUSION: The prevalence of metabolic syndrome was higher in KEs than in host
      country residents in Japan but not in China. Abdominal obesity and triglyceride
      are both discriminating and influential components in metabolic syndrome.

PMID- 21191456
TI  - Cardiovascular risk factors for incident hypertension in the prehypertensive
      population.
AB  - OBJECTIVES: The aim of this study was to investigate the effect of changes in
      cardiovascular disease (CVD) risk factors on progression from prehypertension
      (PreHTN) to hypertension (HTN) using an 8-yr prospective Korean Cancer Prevention
      Study (KCPS) by the National Health Insurance Corporation (NHIC) in Korea.
      METHODS: A total of 16,229 subjects, aged 30 to 54, with new onset preHTN at
      baseline (1994-1996) in a biennial national medical exam were selected and
      followed up till 2004 at 2-yr intervals. All subjects underwent a biennial health
      examination including biochemical measurements and behavior. The log-rank test
      was performed to assess the relationship between changes in CVD risk factors and
      progression to HTN. The Cox proportional hazard model was used to identify
      factors influencing progression to HTN. RESULTS: With regards the progression
      rate in men, ex-smokers (42.9%), abstainers (37.5%), and regular exercisers
      (37.6%) showed a slower progression rate than continuous smokers (49.5%) and
      continuous drinkers (50.9%). In women, those who participated in regular exercise
      (22.6%) had a lower rate of progression than continuous non-exercisers (36.1%).
      According to the results of the Cox proportional hazard model, improvements in
      smoking (hazard ratio [HR], 0.756), drinking (HR, 0.669), regular exercise (HR,
      0.653), body mass index (HR, 0.715), and total cholesterol (HR, 0.788) played a
      protective role in progression to HTN in men, while in women, participating in
      regular exercise (HR, 0.534) was beneficial. CONCLUSION: Improvements in CVD
      related behaviors diminished the progression rate of HTN. This study suggests
      that individuals with PreHTN should be targeted for specific health behavioral
      intervention to prevent the progression of HTN.

PMID- 21191459
TI  - In-Flight Transmission of Novel Influenza A (H1N1).
AB  - The Korea Centers for Disease Control and Prevention confirmed two patients, who
      had taken the same plane from Los Angeles to Seoul, with novel influenza A
      (H1N1). Through contact tracing, we concluded that the second patient was
      infected during the flight.

PMID- 21191460
TI  - Association between Alcohol Intake and Abdominal Obesity among the Korean
      Population.
AB  - OBJECTIVES: Although abdominal obesity has been reported to be highly related
      with alcohol intake, the results are still inconclusive. Therefore, this study
      was conducted to explore the association between alcohol and abdominal obesity
      among the Korean population. METHODS: This study included 8,603 participants
      (men: 5,195, women: 3,408) aged 30 to 87 who visited the health promotion centers
      in Seoul for routine health examinations from April, 2006 to June, 2007.
      Abdominal obesity was defined as WC >=90 cm for men and >=85 cm for women in
      accordance with the Korean Society for the Study of Obesity. For ever drinkers,
      total alcohol consumption in grams was classified into four groups (group 1, non
      drinkers; group 2, 1-10 g of alcohol per day; group 3, 11-20 g of alcohol per
      day; and group 4, over 20 g of alcohol per day). RESULTS: The mean age of the
      study population was 45.4 yr old (men) and 45.3 yr (women). The average waist
      circumference was 85.3 cm in men and 75.3 cm in women. A high alcohol intake was
      associated with high waist circumference in both genders. In multivariate
      analysis, the group of men and women drinkers consuming >20 g in a day had a
      large waist circumference compared with men and women non-drinkers. CONCLUSION:
      This study showed that a high alcohol intake was related to high waist
      circumference. Such association remained independently even after adjustment for
      smoking, which is strongly related to abdominal obesity.

PMID- 21191461
TI  - Condom Use and Prevalence of Genital Chlamydia trachomatis Among the Korean
      Female Sex Workers.
AB  - OBJECTIVES: Since 2004, availability of resources for preventing sexually
      transmitted diseases in Korean female sex workers (FSWs) has decreased because of
      strict application of a law against prostitution. This study is to evaluate the
      condom use and prevalence of Chlamydia trachomatis among FSWs in Korea. METHODS:
      We performed a cross-sectional study of FSWs from 15 major sex work sites in
      Korea from June to November 2008, using convenience sampling. Self-administered
      questionnaires and urine samples were collected after all participants' written
      informed consent. Urine samples were analyzed with PCR at a single central
      laboratory. RESULTS: Among 1,086 FSWs who consented to study participation, data
      from 999 FSWs were appropriate for analysis. C. trachomatis prevalence was 12.8%
      (95% CI: 10.7-14.9%). Younger age increased risk for C. trachomatis. Whereas
      majority of FSWs (71.0%) answered high self confidence in condom negotiation, the
      proportion of FSWs who always used condoms last month was only 23.7%. However,
      practicing regular condom use showed significant protection against chlamydia
      infection, not self confidence in condom negotiation. CONCLUSION: In Korea, FSWs
      were not practicing enough self-protection at work with a high prevalence of C.
      trachomatis. Education for constant practice of protection against sexually
      transmitted diseases is needed, especially for younger FSWs.

PMID- 21191462
TI  - The Associations between Social Support, Health-Related Behaviors, Socioeconomic
      Status and Depression in Medical Students.
AB  - OBJECTIVES: The objective of this study was to estimate the prevalence of
      depression in medical students and to evaluate whether interpersonal social
      support, health-related behaviors, and socio-economic factors were associated
      with depression in medical students. METHODS: The subjects in this study were 120
      medical students in Seoul, Korea who were surveyed in September, 2008. The
      subjects were all women and over the age of 20. Their age, body mass index (BMI),
      quality of sleep, diet, household income, smoking, alcohol consumption, exercise
      levels, and self-reported health status were surveyed. The degree of perceived
      social support was measured using the interpersonal support evaluation list
      (ISEL). Depression was evaluated using the center for epidemiology studies
      depression scale (CES-D). RESULTS: The mean CES-D score was 14.1+/-8.6 and 37.1%
      of the participants appeared to suffer from depression. Low levels of perceived
      interpersonal support increased the risk of depression by more than 10 times and
      having higher household income did not necessarily decrease the risk of
      depression. CONCLUSION: Medical students have a relatively high level of
      depression. Efforts should be made to encourage social support in order to
      promote mental health in medical students.

PMID- 21191464
TI  - Welcome to epidemiology and health.
AB  - The Korean Society of Epidemiology publishes a scholarly journal titled 'Korean
      Journal of Epidemiology', which announces and discusses the results of
      epidemiological studies from the past 30 yr. Since its first publication in 1979,
      the journal has contributed to the advancement of epidemiology as well as the
      prevention and control of disease, and the promotion of health in Korea.In 2009,
      the editorial board has decided to publish the journal in English to contribute
      internationally, and change the journal's name. The new name of the journal is
      'Epidemiology and Health'.The abstract and full text of articles will be
      published as an open access online journal, which will be posted onto the
      homepage (http://www.e-epih.org/) in real time for anyone in the world to access
      free of charge. Our editorial policy is that 'Epidemiology and Health' is open to
      every researcher in fields related to epidemiology, regardless of membership, his
      or her major and nationality.Editorials, lectures, review papers, original
      articles, epidemic and case investigations, brief communications and letters will
      be published to generate active discussion through the journal along with the
      publication of the papers.'Epidemiology and Health' welcomes articles from
      various fields of epidemiology, such as 1) infectious diseases epidemiology, 2)
      chronic diseases epidemiology, 3) nutritional epidemiology, 4) clinical
      epidemiology, 5) pharmacoepidemiology, 6) genetic or molecular epidemiology, 7)
      social epidemiology, 8) environmental or occupational epidemiology, 9)
      epidemiological methods and biostatistics, 10) disease prevention and control,
      11) health promotion and, 12) all other fields related to epidemiology.

PMID- 21191463
TI  - Association of Subway Driver's Depressive Symptoms and Experience of Work-Related
      Problems.
AB  - OBJECTIVES: Subway drivers experience various types of work-related problems
      during their driving, and those experiences can act as risk factors for
      depressive symptoms. This study was conducted to investigate the association
      between work-related problems and subway driver's depressive symptoms. METHODS:
      We recruited all of the 961 current subway drivers of a subway company located in
      Seoul, South Korea and conducted a survey of their socio-demographic and
      vocational characteristics, hospital visits as an outpatient or inpatient, and
      work-related problem experiences during the last year. Work-related problems
      included an accident resulting in death or injury, a conflict with a customer, a
      sudden stop from an emergency bell, or a near accident. Depressive symptoms were
      measured with the Center for Epidemiologic Studies-Depression (CES-D) instrument.
      The survey was performed using a self-report questionnaire from April 16 to July
      13, 2007. The data of 827 drivers (86.2%) were analyzed. RESULTS: Experience of a
      conflict with a passenger (p=0.011), a sudden stop from an emergency bell
      (p=0.001), or a near accident (p=0.001) increased the prevalence of depressive
      symptoms among subway drivers. A multiple logistic regression analysis revealed
      that a sudden stop from an emergency bell increased the risk of depressive
      symptoms significantly (OR=2.59, p=0.026). Near accidents were marginally
      associated with a higher risk for depressive symptoms (OR=1.62, p=0.062).
      CONCLUSION: The experience of a sudden stop from an emergency bell increased
      subway driver's depressive symptoms, and near accidents may increase the risk of
      depressive symptoms. Therefore, interventions for the drivers who had experienced
      these work-related problems are needed.

PMID- 21191465
TI  - Relationship Between Earlobe Crease and Brachial-ankle Pulse Wave Velocity in Non
      hypertensive, Non-diabetic Adults in Korea.
AB  - OBJECTIVES: Several studies have found a significant association between the
      presence of earlobe crease (ELC) and cardiovascular disease (CVD). Brachial-ankle
      Pulse Wave Velocity (baPWV) is a non-invasive and useful measure of arterial
      stiffness predicting cardiovascular events and mortality. However, few studies
      have reported the relationship between ELC and baPWV as a new measure of arterial
      stiffness. The purpose of this study was to determine whether ELC is related to
      baPWV in non-diabetic, non-hypertensive, and apparently healthy Korean adults.
      METHODS: A cross-sectional study was conducted on 573 non-hypertensive, non
      diabetic Korean adults aged 20-80 yr. Subjects were stratified into three groups
      according to gender and menopausal status. baPWV was measured by an automatic
      waveform analyser. The association between ELC and baPWV was assessed by multiple
      linear regression analysis after adjusting for conventional cardiovascular
      disease risk factors including age, gender, blood pressure, lipid profile, and
      smoking status etc. RESULTS: The overall frequency of ELC was 19.02% and the
      subjects with ELC showed significantly higher mean baPWV (p<0.0001). Multiple
      linear regression of subjects revealed that the presence of ELC was independently
      associated with baPWV (male, p<0.0001; premenopausal female p=0.0162;
      postmenopausal female p=0.0208). CONCLUSION: ELC had a significant correlation
      with baPWV, independently controlling for other classical cardiovascular risk
      factors in adults aged 20 yr or older. ELC is an important surrogate marker of
      increased arterial stiffness as measured by baPWV in Korean adults.

PMID- 21191466
TI  - Hepatitis A Vaccination Rates and Related Factors in a 2005 Population-based
      Study in Nonsan, Korea.
AB  - OBJECTIVES: The incidence of clinical hepatitis A has increased in young Korean
      adults since the mid-1990s. Although hepatitis A vaccinations have been
      administered in private clinics over the past 10 yr, no data exist on the
      vaccination rate and relating factors. METHODS: In 2005, a population-based
      survey of 12-35-month-old children was carried out in Nonsan, Korea. An interview
      survey was completed for 71.3% of the children. All data came from a vaccination
      card or confirmation from a provider. RESULTS: The hepatitis A vaccination rate
      was 42.3% for >=1 dose and 24.7% for 2-dose. The results of the multivariate
      regression analysis for the hepatitis A vaccination showed that the second
      (OR=1.6) and third and successive children (OR=3.3) were less often immunized
      than the first child. Low economic status (OR=1.6), rural area (OR=1.5) and
      employed mother (OR=1.5) were also correlated with a lower vaccination rate. The
      hepatitis A vaccination rate was significantly lower in children who had no other
      vaccinations: measlesmumps-rubella (OR=2.8 for >=1 dose and 7.3 for 2-dose),
      varicella (OR=20.2 and 22.0, respectively) and Haemophilus influenza type b
      (OR=14.3 and 13.3, respectively). CONCLUSION: To prevent outbreaks of clinical
      hepatitis A by enough herd immunity, a vaccination should be included in the
      National Immunization Program and a vaccination policy developed and implemented
      that can overcome the barriers to immunization such as late birth order and a
      mother's employment.

PMID- 21191467
TI  - Validity of Stature-predicted Equations using Knee Height for Elderly and
      Mobility Impaired Persons in Koreans.
AB  - OBJECTIVES: This study aimed to establish a stature-predicted equation using knee
      height, and perform a clinical validation on a Korean population. METHODS: Using
      nationwide data obtained from 'Size Korea 2004', a stature-predicted equation was
      drawn and cross validation was performed using knee height in 5,063 subjects
      (2,532 males, 1,785 premenopausal females, and 746 postmenopausal females) who
      were aged between 20 and 69 yr. The formula was then applied to an elderly group
      (7 males and 26 females) and a mobility-impaired group (25 males and 14 females)
      in a real clinical setting. A stature-predicted equation was estimated using knee
      height and age based on multiple linear regression analysis. Cross validation was
      performed using paired t-test, and validation using clinical data was performed
      using Wilcoxon signed rank test. RESULTS: In three groups (males, premenopausal
      females, and postmenopausal females), a cross validation was performed for a
      stature-predicted equation which was drawn using knee height and age. There were
      no significant differences between recorded height and estimated height in the
      elderly group (mean difference+/-interquartile range (IQR): male 0.65+/-4.65 cm,
      female -0.10+/-3.65 cm) and the mobility-impaired group (mean difference+/-IQR:
      male -0.23+/-5.45 cm, female 1.64+/-5.36 cm). CONCLUSION: If several limitations
      could be overcome, the Korean-specific equations using knee height drawn from
      this study could be applied to actual clinical settings with Korean elderly or
      mobility-impaired people.

PMID- 21191468
TI  - Synthesis, Characterization and Biosensing Application of Photon Upconverting
      Nanoparticles.
AB  - Phosphor/fluorescent molecules/particles have been widely used in various
      applications for quite some time. Typically, light with longer wavelength(s) is
      emitted when excited by shorter wavelength light. The opposite effect also
      exists, where a phosphor particle is excited with an infrared or red light and
      emits color(s) of shorter wavelengths, a process called up-conversion. Materials
      with upconverting properties have narrower absorption and line emission spectra
      than their down-converting counterparts. Because most non-target materials in a
      complex mixture do not possess such photon up-conversion properties, a
      dramatically improved S/N ratio is expected in sensing and luminescence reporting
      applications. This makes photon upconverting materials ideal for identification
      of trace amounts of target molecules. Here we report the synthesis,
      characterization and DNA detection application based on NaYF(4):Yb(3+), Er(3+)
      photon upconverting nanoparticles. The design of a nucleotide sensor for the
      detection of point mutation associated with sickle cell disease is described. The
      underlying principle for the detection is luminescence resonance energy transfer
      (LRET), with the photon upconverting nanoparticle as the donor and a dye,
      N,N,N',N'-tetramethyl-6-carboxyrhodamine (TAMRA), as the acceptor. The detection
      scheme is based on a sandwich-type hybridization format. The presence of the
      target DNA is indicated by the increase of the normalized acceptor's emission.
      Based on photon upconverting nanoparticles, which display high S/N ratio and no
      photobleaching, the DNA sensor demonstrates high sensitivity and specificity. The
      results demonstrate great potential of such nanomaterials as oligonucleotide
      sensors.

PMID- 21191469
TI  - Synthesis of a Benzodiazepine-derived Rhodium NHC Complex by C-H Bond Activation.
AB  - The synthesis and characterization of a Rh(I)-NHC complex generated by C-H
      activation of 1,4-benzodiazepine heterocycle are reported. This complex
      constitutes a rare example of a carbene tautomer of a 1,4-benzodiazepine aldimine
      stabilized by transition metal coordination and demonstrates the ability of the
      catalytically relevant RhCl(PCy(3))(2) fragment to induce NHC-forming
      tautomerization of heterocycles possessing a single carbene-stabilizing
      heteroatom. Implications for the synthesis of benzodiazepines and related
      pharmacophores via C-H functionalization are discussed.

PMID- 21191470
TI  - Interpersonal Psychotherapy for Co-occurring Depression and Chronic Pain.
AB  - Up to 37% of individuals experience chronic pain during their lifetimes.
      Approximately one-fourth of primary care patients with chronic pain also meet
      criteria for major depression. Many of these individuals fail to receive
      psychotherapy or other treatment for their depression; moreover when they do,
      physical pain is often not addressed directly. Women, socioeconomically
      disadvantaged individuals, African Americans and Latinos all report higher rates
      of pain and depression compared to other groups. This article describes a version
      of Interpersonal Psychotherapy tailored for patients with comorbid depression and
      chronic pain, Interpersonal Psychotherapy for Depression and Pain (IPT-P). While
      IPT-P potentially could be delivered to many different patient populations in a
      range of clinical settings, this article focuses on its delivery within primary
      care settings for socioeconomically disadvantaged women. Adaptations include a
      brief 8-session protocol that incorporates strategies for anticipating barriers
      to psychotherapy, accepting patients' conceptualization of their difficulties,
      encouraging patients to consider the impact of their pain on their roles and
      relationships, emphasizing self-care, incorporating pain management techniques,
      and flexible scheduling. In addition, IPT-P is designed as an adjunct to usual
      medical pain treatment, and seeks to engage non-treatment seeking patients in
      psychotherapy by focusing on accessibility and relevance of the intervention to
      concerns common among patients with pain. Identifying patients with comorbid
      depression and chronic pain and offering IPT-P as a treatment option has the
      potential to improve clinical outcomes for individuals with depression and
      chronic pain.

PMID- 21191471
TI  - Familial Aspects of Chronic Lymphocytic Leukemia, Monoclonal B-Cell Lymphocytosis
      (MBL), and Related Lymphomas.
AB  - Families with multiple individuals affected with chronic lymphocytic leukemia
      (CLL) and other related B-cell tumors have been described in the literature.
      Familial CLL does not appear to differ from sporadic CLL in terms of prognostic
      markers and clinical outcome. While some environmental factors (such as farming
      related exposures and occupational chemicals) may increase risk of CLL, results
      of epidemiological studies have been generally inconsistent inconsistent and well
      defined extrinsic risk factors are unknown. Large, population-based case-control
      and cohort studies have also shown significant familial aggregation of CLL and
      related conditions including non-Hodgkin lymphomas, especially other indolent
      lymphomas. The precursor condition, monoclonal B-cell lymphocytosis (MBL) also
      aggregates in CLL families. However because the baseline population risks for CLL
      and other indolent lymphomas are low, the absolute risk to a first-degree
      relative for developing CLL or a related disease is also low. Linkage studies
      have been conducted in high-risk CLL families to screen the whole genome for loci
      that contribute to susceptibility but no gene mutations have yet been identified
      by this method. Association studies of candidate genes have implicated several
      genes as being important in CLL but more studies are needed to verify these
      findings. Results from whole genome association are promising. The ability to
      conduct large scale genomic studies will play an important role in detecting
      susceptibility genes for CLL over the next few years and thereby help to
      delineate etiologic pathways.

PMID- 21191472
TI  - Genetic Association Between the COMT Genotype and Urinary Levels of Tea
      Polyphenols and Their Metabolites among Daily Green Tea Drinkers.
AB  - Available in vitro and animal studies have shown cancer protective effects of tea
      polyphenols. Recent study suggests a greater protective effect of green tea
      intake on breast cancer risk among women possessing the low-activity associated
      genotype of the catechol-O-methyltransferase (COMT), which may modulate the
      metabolism and excretion of tea polyphenols through urine. To determine the
      effect of COMT genotype on urinary excretion of tea polyphenol metabolites of
      daily green tea drinkers, a cross-sectional analysis was performed within the
      Shanghai Cohort Study, a population-based, prospective investigation of diet and
      cancer in 18,244men. In addition to an in-person interview, each participant
      provided a blood and urine sample at baseline. In the present study, COMT
      genotype (rs4680) and five urinary metabolites of tea polyphenols were determined
      in 660 cohort subjects who self-identified as daily drinkers of green tea. All
      urinary tea polyphenol measurements were expressed in units of urinary
      creatinine. Men possessing the homozygous low-activity associated COMT genotype
      (LL) exhibited statistically significantly lower urinary levels of individual as
      well as all of the five tea polyphenol metabolites under study relative to
      individuals possessing the wild type high-activity associated COMT genotype
      (HH)or the heterozygous variant genotype (HL). Levels of urinary tea polyphenol
      metabolites were comparable between men possessing the HH and HL genotypes. The
      present study demonstrated that men carrying low-activity associated COMT
      genotype excreted less tea polyphenols from urine, which suggests that they may
      retain more tea polyphenols in their bodies and derive greater health benefits
      from green tea intake.

PMID- 21191473
TI  - Neurohospitalists: Challenges for the Integration of a New Field: A
      Neurointensivist's Perspective.

PMID- 21191474
TI  - Waiting is the Hardest Part: Comparison of Two Computational Strategies for
      Performing a Compelled-Response Task.
AB  - The neural basis of choice behavior is commonly investigated with tasks in which
      a subject analyzes a stimulus and reports his or her perceptual experience with
      an appropriate motor action. We recently developed a novel task, the compelled
      saccade task, with which the influence of the sensory information on the
      subject's choice can be tracked through time with millisecond resolution, thus
      providing a new tool for correlating neuronal activity and behavior. This
      paradigm has a crucial feature: the signal that instructs the subject to make an
      eye movement is given before the cue that indicates which of two possible choices
      is the correct one. Previously, we found that psychophysical performance in this
      task could be accurately replicated by a model in which two developing oculomotor
      plans race to a threshold and the incoming perceptual information differentially
      accelerates their trajectories toward it. However, the task design suggests an
      alternative mechanism: instead of modifying an ongoing oculomotor plan on the fly
      as the sensory information becomes available, the subject could try to wait,
      withholding the oculomotor response until the sensory cue is revealed. Here, we
      use computer simulations to explore and compare the performance of these two
      types of model. We find that both reproduce the main features of the
      psychophysical data in the compelled-saccade task, but they give rise to distinct
      behavioral and neurophysiological predictions. Although, superficially, the
      waiting model is intuitively appealing, it is ultimately inconsistent with
      experimental results from this and other tasks.

PMID- 21191476
TI  - Brain connectivity in pathological and pharmacological coma.
AB  - Recent studies in patients with disorders of consciousness (DOC) tend to support
      the view that awareness is not related to activity in a single brain region but
      to thalamo-cortical connectivity in the frontoparietal network. Functional
      neuroimaging studies have shown preserved albeit disconnected low-level cortical
      activation in response to external stimulation in patients in a "vegetative
      state" or unresponsive wakefulness syndrome. While activation of these "primary"
      sensory cortices does not necessarily reflect conscious awareness, activation in
      higher-order associative cortices in minimally conscious state patients seems to
      herald some residual perceptual awareness. PET studies have identified a
      metabolic dysfunction in a widespread frontoparietal "global neuronal workspace"
      in DOC patients including the midline default mode network ("intrinsic" system)
      and the lateral frontoparietal cortices or "extrinsic system." Recent studies
      have investigated the relation of awareness to the functional connectivity within
      intrinsic and extrinsic networks, and with the thalami in both pathological and
      pharmacological coma. In brain damaged patients, connectivity in all default
      network areas was found to be non-linearly correlated with the degree of clinical
      consciousness impairment, ranging from healthy controls and locked-in syndrome to
      minimally conscious, vegetative, coma, and brain dead patients. Anesthesia
      induced loss of consciousness was also shown to correlate with a global decrease
      in cortico-cortical and thalamo-cortical connectivity in both intrinsic and
      extrinsic networks, but not in auditory, or visual networks. In anesthesia,
      unconsciousness was also associated with a loss of cross-modal interactions
      between networks. These results suggest that conscious awareness critically
      depends on the functional integrity of thalamo-cortical and cortico-cortical
      frontoparietal connectivity within and between "intrinsic" and "extrinsic" brain
      networks.

PMID- 21191477
TI  - Effects of Visual Experience on the Human MT+ Functional Connectivity Networks:
      An fMRI Study of Motion Perception in Sighted and Congenitally Blind Individuals.
AB  - Human middle temporal complex (hMT+) responds also to the perception of non
      visual motion in both sighted and early blind individuals, indicating a
      supramodal organization. Visual experience, however, leads to a segregation of
      hMT+ into a more anterior subregion, involved in the supramodal representation of
      motion, and a posterior subregion that processes visual motion only. In contrast,
      in congenitally blind subjects tactile motion activates the full extent of hMT+.
      Here, we used fMRI to investigate brain areas functionally connected with the two
      hMT+ subregions (seeds) during visual and tactile motion in sighted and blind
      individuals. A common functional connectivity network for motion processing,
      including bilateral ventral and dorsal extrastriate, inferior frontal, middle and
      inferior temporal areas, correlated with the two hMT+ seeds both in sighted and
      blind individuals during either visual or tactile motion, independently from the
      sensory modality through which the information was acquired. Moreover, ventral
      premotor, somatosensory, and posterior parietal areas correlated only with the
      anterior but not with the posterior portion of hMT+ in sighted subjects, and with
      both hMT+ seeds in blind subjects. Furthermore, a correlation between middle
      temporal and occipital areas with primary somatosensory seeds was demonstrated
      across conditions in both sighted and blind individuals, suggesting a cortico
      cortical pathway that conveys non-visual information from somatosensory cortex,
      through posterior parietal regions, to ventral extrastriate cortex. These
      findings expand our knowledge about the development of the functional
      organization within hMT+ by showing that distinct patterns of brain functional
      correlations originate from the anterior and posterior hMT+ subregions as a
      result of visual experience.

PMID- 21191479
TI  - Insulin modulation of magnetoencephalographic resting state dynamics in lean and
      obese subjects.
AB  - Lean and obese subjects can exhibit differences in neuronal activity during
      resting state and tasks. Changes in hormonal status and their action related to
      increased body weight may be the determining factor for these differences. One
      prime candidate is insulin, which until recently was mainly related to its
      metabolic function for the transport and regulation of glucose in the periphery.
      However insulin also acts as an anorexic signal in the central nervous system
      contributing to the termination of food intake in the postprandial state. In our
      study, we examined with whole-head magnetoencephalography the effect of
      intranasal insulin on the dynamics of the resting state network in a placebo
      controlled study. Weighted clustering coefficient C, which describes local
      interconnectedness, and weighted path length L, a measure of global
      interconnectedness, were computed. These parameters showed high intraindividual
      reliability. However, no difference for the network dynamics was found between
      lean and obese subjects in the basal state. The application of insulin led to
      subject specific changes and we found a statistically significant positive
      correlation between the insulin induced change in path length in the theta band
      (4-8 Hz) and body mass index. The change in pathway length after insulin
      administration indicates a strong insulin modulation on global communication
      efficiency, which is probably related to the signaling between different regions
      involved in satiation and homeostatic control.

PMID- 21191478
TI  - Tomosyn expression pattern in the mouse hippocampus suggests both presynaptic and
      postsynaptic functions.
AB  - The protein tomosyn decreases synaptic transmission and release probability of
      vesicles, and is essential for modulating synaptic transmission in neurons. In
      this study, we provide a detailed description of the expression and localization
      patterns of tomosyn1 and tomosyn2 in the subareas of the mouse hippocampus. Using
      confocal and two-photon high-resolution microscopy we demonstrate that tomosyn
      colocalizes with several pre- and postsynaptic markers and is found mainly in
      glutamatergic synapses. Specifically, we show that tomosyn1 is differentially
      distributed in the mouse hippocampus and concentrated mainly in the hilus and
      mossy fibers. Surprisingly, we found that tomosyn2 is expressed in the subiculum,
      CA1 and CA2 pyramidal cell bodies, dendrites and spines, and colocalizes with
      PSD95, suggesting a postsynaptic role. These results suggest that in addition to
      the well-characterized presynaptic function of tomosyn in neurotransmitter
      release, tomosyn2 might have a postsynaptic function, and place tomosyn as a more
      general regulator of synaptic transmission and plasticity.

PMID- 21191480
TI  - Perceptions of, and reactions to, environmental heat: a brief note on issues of
      concern in relation to occupational health.
AB  - Average temperatures around the world are already increasing, and climate change
      projections suggest that global mean temperatures will continue to rise. As the
      effects, and projected effects, of climate change are becoming clearer, it is
      more apparent that the health effects of heat exposure will need further
      investigation. The risks associated with heat exposure are especially relevant to
      understandings of occupational health for people involved in labouring or
      agricultural work in low-income countries. This review is a partial look at the
      ways in which issues surrounding heat exposure and occupational health have been
      treated in some of the available literature. This literature focuses on military
      related medical understandings of heat exposure as well as heat exposure in
      working environments. The ways that these issues have been treated throughout the
      literature reflect the ways in which technologies of observation are intertwined
      with social attitudes. The effects of heat on the health of working people, as
      well as identification of risk groups, will require further research in order to
      promote prophylactic measures as well as to add to understandings of the actual
      and potential consequences of climatic change.

PMID- 21191475
TI  - The intense world theory - a unifying theory of the neurobiology of autism.
AB  - Autism covers a wide spectrum of disorders for which there are many views,
      hypotheses and theories. Here we propose a unifying theory of autism, the Intense
      World Theory. The proposed neuropathology is hyper-functioning of local neural
      microcircuits, best characterized by hyper-reactivity and hyper-plasticity. Such
      hyper-functional microcircuits are speculated to become autonomous and memory
      trapped leading to the core cognitive consequences of hyper-perception, hyper
      attention, hyper-memory and hyper-emotionality. The theory is centered on the
      neocortex and the amygdala, but could potentially be applied to all brain
      regions. The severity on each axis depends on the severity of the molecular
      syndrome expressed in different brain regions, which could uniquely shape the
      repertoire of symptoms of an autistic child. The progression of the disorder is
      proposed to be driven by overly strong reactions to experiences that drive the
      brain to a hyper-preference and overly selective state, which becomes more
      extreme with each new experience and may be particularly accelerated by
      emotionally charged experiences and trauma. This may lead to obsessively detailed
      information processing of fragments of the world and an involuntarily and
      systematic decoupling of the autist from what becomes a painfully intense world.
      The autistic is proposed to become trapped in a limited, but highly secure
      internal world with minimal extremes and surprises. We present the key studies
      that support this theory of autism, show how this theory can better explain past
      findings, and how it could resolve apparently conflicting data and
      interpretations. The theory also makes further predictions from the molecular to
      the behavioral levels, provides a treatment strategy and presents its own
      falsifying hypothesis.

PMID- 21191481
TI  - TNF-alpha and Microglial Hormetic Involvement in Neurological Health & Migraine.
AB  - Environmental enrichment, i.e., increased intellectual, social, and physical
      activity makes brain more resilient to subsequent neurological disease. The
      mechanisms for this effect remain incompletely defined, but evidence shows tumor
      necrosis factor-alpha (TNF-alpha) is involved. TNF-alpha, at acutely high levels,
      possesses the intrinsic capacity to enhance injury associated with neurological
      disease. Conversely, the effect of TNF-alpha at low-levels is nutritive over
      time, consistent with physiological conditioning hormesis. Evidence shows that
      neural activity triggers low-level pro-inflammatory signaling involving TNF
      alpha. This low-level TNF-alpha signaling alters gene expression, resulting in an
      enhanced resilience to disease. Brain-immune signaling may become maladaptive
      when increased activity is chronic without sufficient periods of reduced activity
      necessary for nutritive adaptation. Such tonically increased activity may
      explain, for example, the transformation of episodic to chronic migraine with
      related increased susceptibility to spreading depression, the most likely
      underlying cause of this malady. Thus, TNF-alpha, whose function is to alter gene
      expression, and its principal cellular source, microglia, seem powerfully
      positioned to orchestrate hormetic immune signaling that establishes the
      phenotype of neurological health and disease from brain activity.

PMID- 21191483
TI  - Stochastic threshold microdose model for cell killing by insoluble metallic
      nanomaterial particles.
AB  - This paper introduces a novel microdosimetric model for metallic nanomaterial
      particles (MENAP)-induced cytotoxicity. The focus is on the engineered insoluble
      MENAP which represent a significant breakthrough in the design and development of
      new products for consumers, industry, and medicine. Increased production is
      rapidly occurring and may cause currently unrecognized health effects (e.g.,
      nervous system dysfunction, heart disease, cancer); thus, dose-response models
      for MENAP-induced biological effects are needed to facilitate health risk
      assessment. The stochasticthresholdmicrodose (STM) model presented introduces
      novel stochastic microdose metrics for use in constructing dose-response
      relationships for the frequency of specific cellular (e.g., cell killing,
      mutations, neoplastic transformation) or subcellular (e.g., mitochondria
      dysfunction) effects. A key metric is the exposure-time-dependent, specific
      burden (MENAP count) for a given critical target (e.g., mitochondria, nucleus).
      Exceeding a stochastic threshold specific burden triggers cell death. For
      critical targets in the cytoplasm, the autophagic mode of death is triggered. For
      the nuclear target, the apoptotic mode of death is triggered. Overall cell
      survival is evaluated for the indicated competing modes of death when both apply.
      The STM model can be applied to cytotoxicity data using Bayesian methods
      implemented via Markov chain Monte Carlo.

PMID- 21191482
TI  - Phytotoxic antibiotic sulfadimethoxine elicits a complex hormetic response in the
      weed lythrum salicaria L.
AB  - In order to evaluate the hormetic response of the weed Lythrum salicaria to drug
      exposure we investigated the effects of the antibiotic Sulfadimethoxine by
      growing Lythrum plants for 28 days on culture media containing different drug
      concentrations (between 0.005 and 50 mg.L(-1)). The antibiotic was absorbed by
      plants and can be found in plant tissue. The plant response was organ-dependent:
      roots, cotyledons and cotyledon petioles, were always affected by a toxic effect,
      whilst internodes and leaves length, showed a variable dose-depending response,
      with an increased growth at the lower drug concentrations and toxic effects at
      the higher ones. This variable response was probably dependant on different
      levels of local contamination resulting from a balance between accumulation rate
      and drug dilution in the increasing plant biomass. As a consequence, drug
      toxicity or hormetic response varied according to concentration and were
      different in each of the examined plant organ/tissue. Thus, even if hormesis can
      be considered a general plant response, each plant organ/tissue responds
      differently, depending on the local drug concentration and exposure time.

PMID- 21191484
TI  - Mean cancer mortality rates in low versus high elevation counties in Texas.
AB  - There is controversy as to whether low levels of radiation (i.e., < 5 rem) pose a
      health risk. This brief inquiry compares archived cancer mortality data in
      counties having relatively low (0-250 feet above sea level), medium (500-1000
      feet above sea level), and high (3000+ feet above sea level) elevations also
      having corresponding greater natural background levels of radiation respectively.
      Cancer mortality was found to be lowest in the high elevation counties (mean =
      58.2) followed by low elevation counties (67.5) and then medium elevation
      counties (70.4). Statistically significant differences were found between low 
      high elevations (p = 0.003), and medium - high elevations (p = 0.010), but not
      between low and medium elevations (p = 0.5). More rigorous research, with an
      accounting of confounding variables, is indicated.

PMID- 21191485
TI  - Modeling Dose-response at Low Dose: A Systems Biology Approach for Ionization
      Radiation.
AB  - For ionization radiation (IR) induced cancer, a linear non-threshold (LNT) model
      at very low doses is the default used by a number of national and international
      organizations and in regulatory law. This default denies any positive benefit
      from any level of exposure. However, experimental observations and theoretical
      biology have found that both linear and J-shaped IR dose-response curves can
      exist at those very low doses. We develop low dose J-shaped dose-response, based
      on systems biology, and thus justify its use regarding exposure to IR. This
      approach incorporates detailed, molecular and cellular descriptions of
      biological/toxicological mechanisms to develop a dose-response model through a
      set of nonlinear, differential equations describing the signaling pathways and
      biochemical mechanisms of cell cycle checkpoint, apoptosis, and tumor incidence
      due to IR. This approach yields a J-shaped dose response curve while showing
      where LNT behaviors are likely to occur. The results confirm the hypothesis of
      the J-shaped dose response curve: the main reason is that, at low-doses of IR,
      cells stimulate protective systems through a longer cell arrest time per unit of
      IR dose. We suggest that the policy implications of this approach are an
      increasingly correct way to deal with precautionary measures in public health.

PMID- 21191486
TI  - Dose-dependency of resveratrol in providing health benefits.
AB  - This review describes the dose-dependent health benefits of resveratrol, a
      polyphenolic antioxidant that is found in a variety of foods, especially grape
      skin and red wine. Resveratrol provides diverse health benefits including
      cardioprotection, inhibition of low-density lipoprotein, activation of nitric
      oxide (NO) production, hindering of platelet aggregation [32] A.A.E. Bertelli,
      D.E. Giovannini, R.L. Caterina, W. Bernini, M. Migliori and M. Fregoni et al.,
      Antiplatelet activity of cis-resveratrol, Drugs Exp Clin Res 22 (1996), pp. 61
      63. View Record in Scopus | Cited By in Scopus (111) and promotion of anti
      inflammatory effects. Studies have shown that at a lower dose, resveratrol acts
      as an anti-apoptotic agent, providing cardioprotection as evidenced by increased
      expression in cell survival proteins, improved postischemic ventricular recovery
      and reduction of myocardial infarct size and cardiomyocyte apoptosis and
      maintains a stable redox environment compared to control. At higher dose,
      resveratrol acts as a pro-apoptotic compound, inducing apoptosis in cancer cells
      by exerting a death signal. At higher doses, resveratrol depresses cardiac
      function, elevates levels of apoptotic protein expressions, results in an
      unstable redox environment, increases myocardial infarct size and number of
      apoptotic cells. At high dose, resveratrol not only hinders tumor growth but also
      inhibits the synthesis of RNA, DNA and protein, causes structural chromosome
      aberrations, chromatin breaks, chromatin exchanges, weak aneuploidy, higher S
      phase arrest, blocks cell proliferation, decreases wound healing, endothelial
      cell growth by fibroblast growth factor-2 (FGF-2) and vascular endothelial growth
      factor, and angiogenesis in healthy tissue cells leading to cell death. Thus, at
      lower dose, resveratrol can be very useful in maintaining the human health
      whereas at higher dose, resveratrol has pro-apoptotic actions on healthy cells,
      but can kill tumor cells.

PMID- 21191487
TI  - Exposure to nanoparticles and hormesis.
AB  - Nanoparticles are particles with lengths that range from 1 to 100 nm. They are
      increasingly being manufactured and used for commercial purpose because of their
      novel and unique physicochemical properties. Although nanotechnology-based
      products are generally thought to be at a pre-competitive stage, an increasing
      number of products and materials are becoming commercially available. Human
      exposure to nanoparticles is therefore inevitable as they become more widely used
      and, as a result, nanotoxicology research is now gaining attention. However,
      there are many uncertainties as to whether the unique properties of nanoparticles
      also pose occupational health risks. These uncertainties arise because of gaps in
      knowledge about the factors that are essential for predicting health risks such
      as routes of exposure, distribution, accumulation, excretion and dose-response
      relationship of the nanoparticles. In particular, uncertainty remains with regard
      to the nature of the dose-response curve at low level exposures below the toxic
      threshold. In fact, in the literature, some studies that investigated the
      biological effects of nanoparticles, observed a hormetic dose-response. However,
      currently available data regarding this topic are extremely limited and
      fragmentary. It therefore seems clear that future studies need to focus on this
      issue by studying the potential adverse health effects caused by low-level
      exposures to nanoparticles.

PMID- 21191488
TI  - Hormetic electric field theory of pattern formation.
AB  - The hormetic morphogen theory of curvature (Fosslien 2009) proposes that hormetic
      morphogen concentration gradients modulate the synthesis of adenosine
      triphosphate (ATP) by cells along the gradients (field cells) and thus regulate
      their proliferation and induce curvature such as vascular wall curvature;
      however, it is unclear whether such morphogen gradients can also determine the
      histological pattern of the walls. Here, I propose that the ATP gradients
      modulate export of H(+) by vacuolar H(+)-ATPase (V-ATPase) located on the surface
      of field cells and generate extracellular ion concentration gradients, ion
      currents and electrical fields along the paths of morphogen gradients. In vitro,
      electrical fields can induce directional migration and elongation of vascular
      cells and align the cells with their long axis perpendicular to electrical field
      vectors (Bai et al. 2004). I suggest that likewise, in vivo vascular transmural
      electrical fields induced by hormetic morphogen concentration gradients can
      modulate cell shape i.e. cell elongation and cell curvature, and determine cell
      orientation. Moreover, I suggest that the electrical fields can modulate
      bidirectional cell migration and cell sorting via dynamic hormetic galvanotaxis
      analogous to in vitro isoelectric focusing in proton gradients, thus, hormetic
      morphogen gradients can determine the curvature of vessel walls and their
      histological patterns.

PMID- 21191489
TI  - Effects of ethanol on the shoaling behavior of zebrafish (danio rerio).
AB  - Ethanol (EtOH) often has stimulatory effects at low doses and inhibitory effects
      at high doses, affecting behavior and physiology of many organisms in a non
      linear manner suggestive of hormesis. Zebrafish (Danio rerio) shoaling was
      studied in adult fish exposed to one of five different EtOH concentrations (v/v):
      0.0% control, 0.125%, 0.25%, 0.5%, and 1.0%. Digital photographs of groups of
      four fish were taken every 2 min, with each trial lasting a total of 12 min. The
      median nearest neighbor distance and shoal area were calculated for each
      photograph. Exposure to 1.0% EtOH inhibited shoaling. In contrast, as predicted
      from hormesis, shoaling was significantly tighter (as measured by nearest
      neighbor distance) at low concentrations (0.125%, 0.25%) compared to the control,
      and a J-shaped dose-response curve was present. A similar pattern occurred for
      shoal area, but in this case the only statistically significant differences were
      between the high concentration and all others.

PMID- 21191490
TI  - Low-dose pretreatment for radiation therapy.
AB  - In radiotherapy, a large radiation dose must be applied to both cancer and
      neighboring healthy cells. Recent experiments have shown that a low dose of
      ionizing radiation turns on certain protective mechanisms that allow a cell to
      better survive a subsequent high dose of radiation. This adaptive response can
      have important and positive consequences for radiotherapy. This paper describes a
      simple change in treatment procedures to make use of these beneficial effects. A
      low dose applied only to the healthy cells will probably produce some damage.
      However, it will also start the adaptive response which will yield increased
      protection when the large therapeutic dose is applied. The resultant immediate
      damage will be thereby reduced as well as the probability that the high dose
      therapy itself will induce a subsequent secondary cancer. After a brief
      historical review, the effects of a low radiation dose on a canine cancer cell
      line will be discussed as well as trials of the suggested pre-dose therapy on
      canine cancer patients undergoing standard radiation therapy.

PMID- 21191491
TI  - An unsung Canadian hero!

PMID- 21191492
TI  - Historic times for the CUA.

PMID- 21191493
TI  - Evaluation and medical management of the kidney stone patient.

PMID- 21191494
TI  - Guidelines for the management of castrate-resistant prostate cancer.

PMID- 21191495
TI  - Peer-reviewed publications by CUA members: then and now.
AB  - OBJECTIVE: The objective of this study was to assess the characteristics of
      publications by members of the Canadian Urological Association (CUA) over a 10
      year period. METHODS: All publications by active CUA members during the periods
      January 1993-December 1994 and January 2003-December 2004 were reviewed. RESULTS:
      Of the 487 active members in 1993-1994, 130 (26.7%) were authors a total of 649
      times in 641 publications. External funding was acknowledged in 195 (30.4%).
      There were 131 observational studies (20.4%), 127 review articles (19.8%), 58
      case reports (9.0%), 37 case series (5.8%), and 21 randomized controlled trials
      (RCTs) (3.3%). Of the 454 active member in 2003-2004, 139 (30.6%) were authors a
      total of 748 times in 705 publications. External funding was acknowledged in 237
      (33.6%). There were 153 observational studies (21.7%), 124 review articles
      (17.6%), 52 case reports (7.4%), 49 case series (7.0%), and 46 RCTs (6.5%). There
      were significantly more RCTs and clinical trials in 2003-2004. The most common
      journal was The Journal of Urology in both eras. There were significantly more
      publications in The Canadian Journal of Urology, the British Journal of Urology
      International and the Journal of Endourology in 2003-2004. There were
      significantly more publications acknowledging industry funding and more
      publications citing more than 1 CUA member in 2003-2004. Publication intensity
      increased significantly from 0.67 to 0.82 publications per member, per year for
      the CUA as a whole. INTERPRETATION: Scholarly activity has remained robust over
      the last decade with over 30% of active CUA members contributing to peer-reviewed
      literature. Higher levels of evidence are now observed with a greater number of
      RCTs. CUA members should be proud of their academic productivity.

PMID- 21191496
TI  - Undeserved authorship: too much of a good thing.

PMID- 21191497
TI  - [Not Available].
AB  - PURPOSE: Cryptorchidism is a rather frequent pathology in urology. It is
      associated with a high risk of infertility and degeneration. It also seems to be
      associated with a high risk of torsion. This entity is poorly studied in the
      literature. We studied the cases of torsion on cryptorchid testicles hospitalized
      at our service, to better characterize this pathology and reduce the rate of
      orchidectomy. METHODS: We underwent a retrospective study of all the cases of
      torsion on a cryptorchid testicle hospitalized in our service of urology between
      1999 and 2007. RESULTS: The age of patients was between 7 months and 39 years.
      Torsion touched the right testicle in 53% of the cases. Patients experienced a
      brutal pain of the inguinal area with an under cutaneous mass inflammatory and a
      painful and empty homolateral scrotum. In 60% of the cases, the diagnosis was
      late and an orchidectomy was carried out. In the other cases, a lowering of the
      testicle was done with the controlateral orchidopexy. CONCLUSION: Even though
      torsions on a cryptorchid testicle are rare, we should not ignore them. The early
      diagnosis will make it possible to save and lower the testicle, and track a
      possible degeneration.

PMID- 21191498
TI  - A rare presentation you want to remember!

PMID- 21191499
TI  - Surgical cryoablation as an option for small renal masses in patients who are not
      ideal partial nephrectomy candidates: intermediate-term outcomes.
AB  - OBJECTIVE: There has been increasing interest in surveillance and ablative
      techniques for small renal masses (SRM), given the increasing number being
      diagnosed at smaller sizes. Of the currently available ablative techniques,
      radiofrequency ablation and cryoablation have been the popular ones. We describe
      our intermediate-term outcomes with using cryoablation for SRM in patients who
      were not ideal candidates for partial nephrectomy. MATERIALS AND METHODS:
      Nineteen patients treated with cryoablation were included. Patients with renal
      lesions <4 cm were considered for cryoablation, and all patients were treated
      between 2002 and 2007. Access was either laparoscopic (transperitoneal) or via
      open surgical techniques. From 2002 to 2004, the CryoCare System (Endocare, Inc.,
      Irvine, CA) was used, with probe sizes ranging from 3 to 5 mm. Before 2004, the
      SeedNet system (Galil Medical, Arden Hills, MN) was used, with 17-gauge (1.47 mm)
      IceRod cryoneedles. Recurrence-free survival (RFS) and overall survival (OS) were
      calculated using Kaplan Meier methodology. RESULTS: The mean age was 56.7 years.
      The mean tumour size was 2.6 cm (range 1.2-4.0 cm). There were no intraoperative
      or postoperative complications in the 19 patients. One patient has been lost to
      follow-up; mean follow up was 41.6 months (range 7-84 months) in the cohort.
      Recurrence, defined as either increase in size of lesion or enhancement on follow
      up imaging, was seen in 4 patients. There was 1 non-cancer specific death, and 1
      cancer specific death. CONCLUSIONS: The 4-year RFS rate and OS rate were 83.6%
      and 94.1%, respectively, in patients with SRM who were unsuitable for partial
      nephrectomy.

PMID- 21191500
TI  - Feasibility and outcome of clean intermittent catheterization for children with
      sensate urethra.
AB  - OBJECTIVE: Clean intermittent catheterization (CIC) is an important asset in
      managing children with noncompliant bladders. We review the feasibility and late
      outcomes of patients with normal urethral sensation who began CIC. MATERIALS AND
      METHODS: We reviewed all patients with posterior urethral valve (PUV) or non
      neuropathic bladder sphincter dysfunction (NNBSD) who began on CIC, and had at
      least 2 years of follow-up. We considered their age, indication, acceptance and
      compliance with CIC. Additionally, we examined the late outcome of bladder
      function and the need for any surgical intervention at follow-up. RESULTS:
      Between 1999 and 2006, 52 patients with PUV (38 patients) or NNBSD (14 patients)
      were started on CIC. Of these 52 patients, 48% were under the age of 4. A total
      of 44 patients (85%) accepted the recommendation for CIC, and 34 patients (65%)
      were compliant with the protocol after at least 2 years of follow-up. The age of
      the patients was the only significant factor related to the success of the
      protocol (4 years old or younger, p = 0.03). After at least 2 years of follow-up,
      28 patients (54%) remained on CIC and have not required urinary diversion or
      bladder reconstruction. CONCLUSION: The current study showed that CIC is a
      feasible option for patients with sensate urethra, which necessitates the
      introduction of treatment as early as possible. Further, those patients who are
      compliant with the CIC demonstrated a better chance of avoiding subsequent
      surgical intervention for the management of a non-compliant bladder.

PMID- 21191501
TI  - Determining compliance in clean intermittent catheterization for children with
      sensate urethra.

PMID- 21191502
TI  - A pioneer of urologic surgery from a small town in Ontario, Canada: A tribute to
      Abraham Groves (1847-1935).
AB  - BACKGROUND: Abraham Groves worked as a general practitioner and surgeon in the
      small town of Fergus, Ontario, Canada. Several priority claims have been
      attributed to Groves' life in surgery, including aseptic surgery (1874),
      appendectomy (1883) and the use of surgical gloves (1885). He was also an early
      practitioner of urological surgery. OBJECTIVE: The purpose of this paper is to
      describe and objectively assess his contributions as a pioneer in urological
      surgery. METHODS: A systematic search of contemporary journals was made for
      articles by or about Groves. These articles and his 1934 autobiography were
      reviewed. The information was assessed not only for priority, but also for the
      development of organized surgical principles and thought. RESULTS: Groves
      published frequently throughout his career; up to this point, 36 papers have been
      identified. Groves' claims are verifiable for aseptic surgery, which were the
      result of logical surgical thought and was practiced throughout his career.
      Contemporary publications support his early use of suprapubic lithotomy (1875),
      prostatotomy (1887), bladder repair (1892), urethral repair (1903), renal
      decapsulation (1905) and prostatectomy (1911). CONCLUSIONS: Despite his
      isolation, Abraham Groves independently developed a full range of surgical
      techniques and principles relevant to modern-day urology. His impact was reduced
      by the nature of the environment in which he worked and by the limited
      circulation of the journals in which he chose to publish.

PMID- 21191503
TI  - A true surgical pioneer.

PMID- 21191504
TI  - Tumour location as a predictor of benign disease in the management of renal
      masses.
AB  - OBJECTIVE: To investigate the association between tumour location and the
      proportion of benign disease in renal masses presumed to be renal cell carcinoma
      (RCC) preoperatively. METHODS: This Institutional Review Board approved study
      includes 196 patients who underwent surgical treatment for renal masses <5 cm at
      our institution by a single surgeon between January 2002 and June 2009. Based on
      preoperative imaging, each mass was designated as central (touching or
      encroaching upon the renal collecting system and/or renal sinus) or peripheral.
      The association between tumour location and benign pathology was determined using
      univariate and multiple logistic regression, including tumour size and patient
      sex in the model. RESULTS: The proportion of histologically confirmed benign
      disease in this series was 11.2%. The proportion of benign disease by location
      was 5.9% and 19.5% for central and peripheral masses, respectively. The effect of
      location was found to have a significant prognostic value (p = 0.0273) with an
      adjusted odds ratio of 3.51 (95% CI = 1.38-19.62) for the odds of a benign
      diagnosis in peripheral compared to central tumours. Tumour size and patient sex
      were not significant predictors of benign pathology (p = 0.483 and 0.191,
      respectively). CONCLUSIONS: Peripherally located renal masses are more likely to
      be benign than centrally located renal masses. This information may be used when
      selecting strategies for the management of renal masses presumed to be RCC.

PMID- 21191505
TI  - Can tumour location predict degree of malignancy in small renal masses?

PMID- 21191506
TI  - The status of pelvic floor muscle training for women.
AB  - There is no consensus on the amount of exercise necessary to improve pelvic floor
      muscle (PFM) function. We reviewed the pathophysiology of PFM dysfunction and the
      evolution of PFM training regimens since Kegel introduced the concept of pelvic
      floor awareness and the benefits of strength. This paper also describes the
      similarities and differences between PFM and other muscular groups, reviews the
      physiology of muscle contraction and principles of muscle fitness and exercise
      benefits and presents the range of protocols designed to strengthen the PFM and
      improve function. We also discuss the potential application of new technology and
      methodologies. The design of PFM training logically requires multiple factors to
      be considered in each patient. Research that defines measures to objectively
      quantify the degree of dysfunction and the efficacy of training would be
      beneficial. The application of new technologies may help this process.

PMID- 21191507
TI  - Should all men having a radical prostatectomy have a pelvic lymph node
      dissection? No.

PMID- 21191509
TI  - Multifocal high-grade prostatic intraepithelial neoplasia is still a significant
      risk factor for adenocarcinoma.

PMID- 21191508
TI  - Why all prostate cancer surgery should include an adequate lymph node dissection.

PMID- 21191510
TI  - A technique using a resectoscope sheath under direct vision and nasogastric tube
      for difficult catheterization following TURP.

PMID- 21191511
TI  - Novel risk markers for gastric cancer screening: Present status and future
      prospects.
AB  - Initial identification of populations at high risk of gastric cancer (GC) is
      important for endoscopic screening of GC. As serum pepsinogen (PG) test-positive
      subjects with progression of chronic atrophic gastritis (CAG) show a high
      likelihood of future cancer development, this population warrants careful follow
      up observation as a high-risk GC group. By combining the PG test with
      Helicobacter pylori (HP) antibody titers, the HP-related chronic gastritis stage
      can be classified, thus identifying not only a GC high-risk group but also a low
      risk group. Among PG test-negative patients without CAG, those with high serum PG
      II levels and HP antibody titers are thought to have severe gastric mucosal
      inflammation and the risk of diffuse-type GC is also high. Meanwhile, in gastric
      mucosae obtained by endoscopic biopsy, HP infection induces aberrant DNA
      methylation in CpG islands in multiple gene regions and the extent of methylation
      clearly correlates with GC risk. By quantifying aberrant DNA methylation in
      suitable gene markers, we can determine the extent of the epigenetic field for
      cancerization. These novel concepts and risk markers will have many clinical
      applications in gastrointestinal endoscopy, including more efficient endoscopic
      GC screening and a strategic approach to metachronous multiple GCs after
      endoscopic treatment.

PMID- 21191513
TI  - Dietary approaches following endoscopic retrograde cholangiopancreatography: A
      survey of selected endoscopists.
AB  - AIM: To describe the dietary recommendations of experienced endoscopists for
      patients who have undergone endoscopic retrograde cholangiopancreatography (ERCP)
      and the factors that influence these recommendations. METHODS: Selected U.S.
      endoscopists with ERCP experience were surveyed by e-mail. A questionnaire with
      three hypothetical ERCP cases of patients at low, medium and high risk for
      development of post-ERCP pancreatitis (PEP) was shown. For each scenario,
      respondents were asked to recommend a post-procedure diet and time to first oral
      intake. Respondents were also asked about the effect of various clinical factors
      on their recommendations, including risk of PEP. RESULTS: 97/187 selected ASGE
      members (51.9%) responded. When risk of PEP was either low, medium or high, 53%,
      88% and 96% recommended a diet of clear liquids/NPO respectively, and 2%, 5% and
      18% recommended delaying first oral intake until the following day. About 88% of
      respondents gave the same type of diet to patients at high as those with moderate
      risk of PEP (P = 0.04). However, 37% and 43% of respondents gave different types
      of diet to patients at low vs moderate-risk and low-risk vs high-risk of PEP
      respectively (P < 0.001). No statistically significant associations were found
      regarding the effect of other clinical factors or respondent demographics.
      CONCLUSION: Most experienced endoscopists limit diet to NPO/clear liquids after
      ERCP for patients at high or moderate risk of post-ERCP pancreatitis. About half
      allow a low-fat or regular diet in patients at low risk.

PMID- 21191512
TI  - Gastroesophageal reflux disease: Important considerations for the older patients.
AB  - Gastroesophageal reflux disease (GERD) is the most common upper gastrointestinal
      disorder seen in the elderly. The worldwide incidence of GERD is increasing as
      the incidence of Helicobacter pylori is decreasing. Although elderly patients
      with GERD have fewer symptoms, their disease is more often severe. They have more
      esophageal and extraesophageal complications that may be potentially life
      threatening. Esophageal complications include erosive esophagitis, esophageal
      stricture, Barrett's esophagus and adenocarcinoma of the esophagus.
      Extraesophageal complications include atypical chest pain that can simulate
      angina pectoris; ear, nose, and throat manifestations such as globus sensation,
      laryngitis, and dental problems; pulmonary problems such as chronic cough,
      asthma, and pulmonary aspiration. A more aggressive approach may be warranted in
      the elderly patient, because of the higher incidence of severe complications.
      Although the evaluation and management of GERD are generally the same in elderly
      patients as for all adults, there are specific issues of causation, evaluation
      and treatment that must be considered when dealing with the elderly.

PMID- 21191514
TI  - Use of endoscopic ultrasound for diagnosis of cholangiocarcinoma in auto-immune
      hepatitis.
AB  - In this report, a patient was exposed to an herbal remedy for
      hypercholesterolemia. She became acutely jaundiced while taking the remedy and
      presented for medical care. Endoscopic ultrasound was utilized, and found a
      distal common bile duct mass. Endoscopic retrograde cholangiopancreatography
      guided bile duct biopsies revealed that the mass was cholangiocarcinoma (CCA).
      This case highlights a unique association between autoimmune hepatitis and CCA.
      It also highlights that EUS can be safely used in patients with cirrhosis to
      spare invasive evaluation such as exploratory laporotomy for diagnosis and
      staging of cholangiocarcinoma.

PMID- 21191515
TI  - Successful type-oriented endoscopic resection for gastric carcinoid tumors: A
      case report.
AB  - The standard treatment in Japan for gastric carcinoid has been gastrectomy with
      lymphadenectomy. This report describes the possibility of endoscopic treatment as
      an appropriate option for gastric carcinoid fulfilling certain conditions. A 46
      year old woman underwent endoscopic mucosal resection for two 3 mm gastric
      carcinoids. The patient had hypergastrinemia with pernicious anemia and type A
      chronic atrophic gastritis, suggesting that the tumors were type I in Rindi's
      classification. Both tumors were located in the mucosal layer with no cellular
      polymorphism and were chromogranin A positive. Neither tumor recurrence in the
      stomach nor distant metastases have been documented during the 5 years of follow
      up. Although many type I gastric carcinoids may be clinically indolent, reports
      on successful endoscopic treatment for this carcinoid have been scanty in the
      literature in Japan, presumably because of the hitherto surgical treatment stance
      for the disease. This report discusses how the size, number, depth and
      histological grading of the type I gastric carcinoid could allow the correct
      identification of a benign or malignant propensity of an individual tumor and how
      endoscopic resection could be a treatment of choice when these factors render it
      feasible. This stance could also obviate unnecessary surgical resection for more
      benign tumors.

PMID- 21191516
TI  - Idiopathic non-hypertrophic pyloric stenosis in an infant successfully treated
      via endoscopic approach.
AB  - Non-peptic, non-hypertrophic pyloric stenosis has rarely been reported in
      pediatric literature. Endoscopic pyloric balloon dilation has been shown to be a
      safe procedure in treating gastric outlet obstruction in older children and
      adults. Partial gastric outlet obstruction (GOO) was diagnosed in an infant by
      history and confirmed by an upper gastrointestinal series (UGI). Abdominal
      ultrasonography and computed tomography scan excluded idiopathic hypertrophic
      pyloric stenosis, abdominal tumors, gastrointestinal and hepato-biliary
      pancreatic anomalies. Endoscopic findings showed a pinhole-sized pylorus and did
      not indicate peptic ulcer disease, Helicobacter pylori infection, antral web, or
      evidence of allergic and inflammatory bowel diseases. Three sessions of a step
      wise endoscopic pyloric balloon dilation were conducted under general anesthesia
      and a fluoroscopy at two week intervals using catheter balloons (Boston
      Scientific Microvasive((r)), MA, USA) of increasing diameters. Repeat UGI after
      the first session revealed normal gastrointestinal transit and no intestinal
      obstruction. The patient tolerated solid food without any gastrointestinal
      symptoms since the first session. The endoscope was able to be passed through the
      pylorus after the last session. Although the etiology of GOO in this infant is
      unclear (proposed mechanisms are herein discussed), endoscopic pyloric balloon
      dilation was a safe procedure for treating this young infant with non-peptic, non
      hypertrophic pyloric stenosis and should be considered as an initial approach
      before pyloroplasty in such presentations.

PMID- 21191517
TI  - Pathological classification of intrahepatic cholangiocarcinoma based on a new
      concept.
AB  - Intrahepatic cholangiocarcinoma (ICC) arises from the lining epithelium and
      peribiliary glands of the intrahepatic biliary tree and shows variable
      cholangiocytic differentiation. To date, ICC was largely classified into
      adenocarcinoma and rare variants. Herein, we propose to subclassify the former,
      based on recent progress in the study of ICC including the gross classification
      and hepatic progenitor/stem cells and on the pathological similarities between
      biliary and pancreatic neoplasms. That is, ICC is classifiable into the
      conventional (bile duct) type, the bile ductular type, the intraductal neoplasm
      type and rare variants. The conventional type is further divided into the small
      duct type (peripheral type) and large bile duct type (perihilar type). The former
      is a tubular or micropapillary adenocarcinoma while the latter involves the
      intrahepatic large bile duct. Bile ductular type resembles proliferated bile
      ductules and shows a replacing growth of the hepatic parenchyma. Hepatic
      progenitor cell or stem cell phenotypes such as neural cell adhesion molecule
      expression are frequently expressed in the bile ductular type. Intraductal type
      includes papillary and tubular neoplasms of the bile duct (IPNBs and ITNBs) and a
      superficial spreading type. IPNB and ITNB show a spectrum from a preneoplastic
      borderline lesion to carcinoma and may have pancreatic counterparts. At invasive
      sites, IPNB is associated with the conventional bile duct ICC and mucinous
      carcinoma. Biliary mucinous cystic neoplasm with ovarian-like stroma in its wall
      is different from IPNB, particularly IPNB showing cystic dilatation of the
      affected ducts. Rare variants of ICC include squamous/adenosquamous cell
      carcinoma, mucinous/signet ring cell carcinoma, clear cell type, undifferentiated
      type, neuroendocrine carcinoma and so on. This classification of ICC may open up
      a new field of research of ICC and contribute to the clinical approach to ICC.

PMID- 21191518
TI  - Spontaneous rupture of hepatic hemangiomas: A review of the literature.
AB  - Hepatic hemangiomas are congenital vascular malformations, considered the most
      common benign mesenchymal hepatic tumors, composed of masses of blood vessels
      that are atypical or irregular in arrangement and size. Hepatic hemangiomas can
      be divided into two major groups: capillary hemangiomas and cavernous hemangiomas
      These tumors most frequently affect females (80%) and adults in their fourth and
      fifth decades of life. Most cases are asymptomatic although a few patients may
      present with a wide variety of clinical symptoms, with spontaneous or traumatic
      rupture being the most severe complication. In cases of spontaneous rupture,
      clinical manifestations consist of sudden abdominal pain, and anemia secondary to
      a haemoperitoneum. Disseminated intravascular coagulopathy can also occur.
      Haemodynamic instability and signs of hypovolemic shock appear in about one third
      of cases. As the size of the hemangioma increases, so does the chance of rupture.
      Imaging studies used in the diagnosis of hepatic hemangiomas include
      ultrasonography, dynamic contrast-enchanced computed tomography scanning,
      magnetic resonance imaging, hepatic arteriography, digital subtraction
      angiography, and nuclear medicine studies. In most cases hepatic hemangiomas are
      asymptomatic and should be followed up by means of periodic radiological
      examination. Surgery should be restricted to specific situations. Absolute
      indications for surgery are spontaneous or traumatic rupture with hemoperitoneum,
      intratumoral bleeding and consumptive coagulopathy (Kassabach-Merrit syndrome).
      In a patient presenting with acute abdominal pain due to unknown abdominal
      disease, spontaneous rupture of a hepatic tumor such as a hemangioma should be
      considered as a rare differential diagnosis.

PMID- 21191519
TI  - Does granulocyte-colony stimulating factor administration induce damage or repair
      response in schistosomiasis?
AB  - AIM: To introduce Granulocyte-colony stimulating factor (G-CSF) as a new
      therapeutic modality for schistosomiasis through stem cell mobilization,
      immunomodulation or fibrosis remodeling. METHODS: In this study, a 5 d course of
      human recombinant G-CSF (100 MUg/kg sc) was applied to Schistosoma mansoni
      infected mice at different stages of disease (5 d before infection as well as 3,
      5 and 7 wk post-infection). The animals were sacrificed at 10 d as well as 4, 6
      and 8 wk post infection. Mice were examined for: (1) Total leukocyte count which
      is an accepted surrogate marker for the stem cell mobilization into the
      circulation; (2) Egg count in intestine and liver tissue to assess the parasitic
      load; and (3) Histopathological changes in Hx/E and Masson trichrome stained
      sections as well as collagen content in Sirius red-stained liver sections to
      determine the severity of liver fibrosis. RESULTS: Mice developed leukocytosis.
      The egg load and the number of granulomas were not affected by the G-CSF
      treatment but there was an obvious change in the composition of granulomas
      towards an increased cellularity. Moreover, fibrosis was significantly decreased
      in treated groups compared to untreated animals (collagen content either
      preinfection or at 3 and 5 wk post infection: 5.8 +/- 0.5, 4.7 +/- 0.5, 4.0 +/-
      0.7 vs 8.2 +/- 0.9; P <= 0.01). CONCLUSION: Although G-CSF did not cause direct
      elimination of the parasite, it enhanced granulomatous reaction and reduced the
      fibrosis. Further investigation of the underlying mechanisms of these two actions
      is warranted.

PMID- 21191520
TI  - Development of osteomalacia in a post-liver transplant patient receiving adefovir
      dipivoxil.
AB  - We report the case of a patient treated with living donor-related liver
      transplantation who suffered from osteomalacia during adefovir dipivoxil (ADV)
      containing antiviral therapy for lamivudine-resistant hepatitis B virus
      infection. The patient had generalized bone pain, with severe hypophosphatemia
      after 20 mo of ADV therapy. Radiographic studies demonstrated the presence of
      osteomalacia. The peak plasma ADV level was 38 ng/mL after administration of ADV
      at 10 mg/d. It was also found that ADV affected the metabolism of tacrolimus, a
      calcineurin-inhibitor, and caused an increase in the plasma levels of tacrolimus.
      The disability was reversed with the withdrawal of ADV and with mineral
      supplementation. ADV can cause an elevation of plasma tacrolimus levels, which
      may be associated with renal dysfunction. High levels of ADV and tacrolimus can
      cause nephrotoxicity and osteomalacia. This case highlights the importance of
      considering a diagnosis of osteomalacia in liver transplantation recipients
      treated with both ADV and tacrolimus.

PMID- 21191521
TI  - Simple nucleos(t)ides as HBV prophylaxis regime of post-liver transplantation:
      Six-year followed up.
AB  - A combination of nucleos(t)ides and hepatitis B immunoglobulin (HBIg) has been
      found to be effective for the prevention of hepatitis B viral (HBV) reinfection
      after liver transplantation (LT), but its administration is costly, and not
      always available. We report the case of a male, 33-year-old cirrhotic patient who
      has tested positive for serum HBsAg, and HBeAg, with 9.04 * 10(7) copies/mL of
      HBV DNA. He suffered from acute liver failure and was near death before
      undergoing emergency LT. No HBIg was available at the time, so only lamivudine
      was used. He routinely received immunosuppression medication. Serum HBV DNA and
      HBsAg still showed positive post-LT, and the graft re-infected. Hepatitis B
      flared three months later. Adefovir dipivoxil was added to the treatment, but in
      the 24(th) mo of treatment, the patient developed lamivudine resistance and a
      worsening of the hepatitis occurred shortly thereafter. The treatment combination
      was then changed to a double dosage of entecavir and the disease was gradually
      resolved. After 60-mo of post-LT nucleos(t)ide analogue therapy, anti-HBs
      seroconverted, and the antiviral was stopped. By the end of a 12-mo follow-up,
      the patient had achieved sustained recovery. In conclusion, the case seems to
      point to evidence that more potent and less resistant analogues like entecavir
      might fully replace HBIg as an HBV prophylaxis and treatment regimen.

PMID- 21191523
TI  - Fundamentals of medical record documentation.

PMID- 21191522
TI  - The genetics of eating disorders.
AB  - The eating disorders anorexia nervosa and bulimia nervosa traditionally have been
      viewed as sociocultural in origin. However, recent behavioral genetic findings
      suggest substantial genetic influence on these disorders. Molecular genetic
      research of these disorders is in its infancy, but initial results are promising.
      This article reviews findings from family, twin, and molecular genetic studies
      that support substantial genetic influences on disordered eating and highlights
      additional areas for future research.

PMID- 21191524
TI  - Hyperprolactinemia associated with risperidone: a case report and review of
      literature.
AB  - This case report describes a 19-year-old Caucasian woman who presented to a state
      psychiatric facility with symptoms of depression and auditory hallucinations. She
      was diagnosed with schizoaffective disorder, depressed type, and was treated with
      risperidone and sertraline. Soon after initiation of drug therapy, the patient
      developed galactorrhea and dysmenorrhea, and her prolactin level was 171.6ng/mL
      (normal level 2.8-29.2ng/mL in adult women). Upon discontinuation of risperidone,
      the prolactin level dropped to 17.2ng/mL within one week. The patient was treated
      with quetiapine and titrated up to 800mg daily. Repeated prolactin levels
      continued to be normal during treatment with quetiapine. This case report and
      others from literature suggest that risperidone is associated with
      hyperprolactinemia, and that quetiapine is less likely to be associated with
      hyperprolactinemia.

PMID- 21191525
TI  - Evidence-based addiction medicine: the use of lofexidine for opioid
      detoxification.
AB  - Is there any evidence that lofexidine is as effective as and better tolerated
      than clonidine for opiate detoxification? Could lofexidine be safely combined
      with other agents in the management of withdrawal? The purpose of this review is
      to seek answers to these postulates by using evidence-based testimony.

PMID- 21191526
TI  - A man develops panic disorder after a car accident: response to supportive
      psychotherapy.
AB  - We will describe psychotherapy with a man who developed panic disorder after a
      motor vehicle accident. Early intervention, selection of therapeutic approach,
      important turning points in the therapy, the decision-making process of combining
      psychotherapy with medication, and successful psychiatric collaboration with the
      primary care physician are discussed.

PMID- 21191527
TI  - Sleep quality and self-harm behaviors among internal medicine outpatients.

PMID- 21191528
TI  - An analysis of the intended use of atypical antipsychotics in dementia.
AB  - In this article, the authors explore trends in intended usage of atypical
      antipsychotics to treat dementia following the United States Food and Drug
      Administration advisory safety warning issued in April 2005. Analysis suggests
      that physician-reported intended usage of antipsychotics to treat dementia has
      declined by nearly 50 percent over the past five years. When reviewing the
      products intended for use in the treatment of patients with dementia, atypical
      intended usage has declined considerably while the intended usage of anti
      Alzheimer's disease treatments has grown to replace those shares.

PMID- 21191529
TI  - Gratitude and well being: the benefits of appreciation.
AB  - The word "gratitude" has a number of different meanings, depending on the
      context. However, a practical clinical definition is as follows-gratitude is the
      appreciation of what is valuable and meaningful to oneself; it is a general state
      of thankfulness and/or appreciation. The majority of empirical studies indicate
      that there is an association between gratitude and a sense of overall well being.
      However, there are several studies that indicate potential nuances in the
      relationship between gratitude and well being as well as studies with negative
      findings. In terms of assessing gratitude, numerous assessment measures are
      available. From a clinical perspective, there are suggested therapeutic exercises
      and techniques to enhance gratitude, and they appear relatively simple and easy
      to integrate into psychotherapy practice. However, the therapeutic efficacy of
      these techniques remains largely unknown. Only future research will clarify the
      many questions around assessment, potential benefits, and enhancement of
      gratitude.

PMID- 21191530
TI  - A Prospective Study Comparing the Long-term Effectiveness of Injectable
      Risperidone Long-acting Therapy and Oral Aripiprazole in Patients with
      Schizophrenia.
AB  - OBJECTIVE: To test the hypothesis that long-term maintenance with injectable
      risperidone long-acting therapy is superior to oral daily aripiprazole in stable
      patients with schizophrenia. DESIGN: This two-year, rater-blinded, open-label,
      multicenter study (NCT00299702) randomized subjects to injectable risperidone
      long-acting therapy (25-50mg, injected every 2 weeks) or oral aripiprazole (5
      30mg/day), with study visits every two weeks. Subjects who met relapse criteria
      or discontinued study drug could remain in the study. SETTING: Clinical trial.
      PARTICIPANTS: Stable subjects with schizophrenia not adequately benefiting from
      current treatment who experienced two or more relapses in the past two years. If
      recently relapsed, subjects were stabilized (per clinician judgment) for two or
      more months before entry. MEASUREMENTS: Primary endpoints: time to relapse and
      time in remission. Safety assessments included adverse event reporting. RESULTS:
      Of 355 subjects randomized, 349 were in the intent-to-treat analysis set. Data
      inspection revealed that 53 (14.9%) randomized subjects deviated from
      inclusion/exclusion criteria, most commonly not meeting stability requirements.
      At baseline, mean (standard deviation [SD]) Positive and Negative Syndrome Scale
      total score was 68.9 (14.6); 115 (33.0%) intent-to-treat subjects met remission
      criteria. Approximately 29 percent in each group discontinued the study before
      completing two years. No significant between-group differences were noted in time
      to relapse or time in remission. No new tolerability issues were identified.
      CONCLUSION: RESULTS failed to demonstrate superiority with injectable risperidone
      long-acting therapy versus oral aripiprazole. The study design did not allow for
      valid conclusions of equivalence or noninferiority. Although this study attempted
      to mimic a real-world treatment setting for stable patients, the broad study
      population, the lack of patient selection for nonadherence, biweekly visits,
      regular assessments, and other design issues limited generalizability and
      interpretation relative to the study hypothesis.

PMID- 21191531
TI  - Scientific Forum on the Diagnostic and Statistical Manual of Mental Disorders,
      Fifth Edition (DSM-V)-An Invitation.
AB  - The publication of the Diagnostic and Statistical Manual of Mental Disorders,
      Fifth Edition (DSM-V) is anticipated in May 2013 with many new additions and
      changes. In this article, the author summarizes the phases of psychiatric
      classification from the turn of the 20th century until today. Psychiatry 2010
      offers a DSM-V Scientific Forum and invites readers to submit comments,
      recommendations, and articles to Psychiatry 2010 and DSM-V Task Force.

PMID- 21191532
TI  - Motor examinations in psychiatry.
AB  - The capacity for voluntary motor activity underpins all behavior. Although
      psychiatrists are acutely aware of behavior, we tend to think of its abstract
      motives more than its concrete mechanisms. This article reviews the basic brain
      mechanisms of voluntary motor activity, the most useful pyramidal tract or upper
      motor neuron signs, and their relevance to specific patient groups of interest to
      psychiatrists.

PMID- 21191533
TI  - Does B12 deficiency lead to lack of treatment response to conventional
      antidepressants?
AB  - We present two cases of treatment-resistant depression that improved with
      recognition and correction of the underlying medical etiology of vitamin B12
      deficiency. Supplementations of vitamin B12 to the same antidepressant regimen
      that the patient had not responded earlier led to response. Two male subjects who
      were vegetarians presented with long-standing histories of depression and had not
      responded to three adequate trials of antidepressants. Upon investigation, the
      authors found that the subjects had low vitamin B12 levels. Both cases improved
      with supplementation of vitamin B12. Subjects with depression who do not respond
      to conventional antidepressants should be evaluated for nutritional factors.

PMID- 21191534
TI  - To report or not to report.

PMID- 21191535
TI  - Humanity, what will you choose-ominous impotence or omnipotence?

PMID- 21191536
TI  - EPH-EPHRIN in human gastrointestinal cancers.
AB  - Ever since its discovery two decades ago, the erythropoietin-producing hepatoma
      (EPH)-EPHRIN system has been shown to play multifaceted roles in human
      gastroenterological cancer as well as neurodevelopment. Over-expression,
      amplification and point mutations have been found in many human cancers and many
      investigators have shown correlations between these up-regulations and tumor
      angiogenesis. Thus, the genes in this family are considered to be potential
      targets of cancer therapy. On the other hand, the down-regulation of some members
      as a result of epigenetic changes has also been reported in some cancers.
      Furthermore, the correlation between altered expressions and clinical prognosis
      seems to be inconclusive. A huge amount of protein-protein interaction studies on
      the EPH-EPHRIN system have provided a basic scheme for signal transductions,
      especially bi-directional signaling involving EPH-ERPHRIN molecules at the cell
      membrane. This information also provides a manipulative strategy for harnessing
      the actions of these molecules. In this review, we summarize the known
      alterations of EPH-EPHRIN genes in human tumors of the esophagus, stomach,
      colorectum, liver and pancreas and present the perspective that the EPH-EPHRIN
      system could be a potential target of cancer therapy.

PMID- 21191538
TI  - Retroperitoneal germ cell tumor diagnosed by endoscopic ultrasound-guided fine
      needle aspiration.
AB  - Isolated extragonadal germ cell tumors can be primary in nature or metastatic
      from a burned out testicular cancer. Accurate diagnosis is critical as
      appropriate therapy can be highly curative. We present the case of an isolated
      extragonadal germ cell tumor in the retroperitoneum diagnosed by endoscopic
      ultrasound-guided fine needle aspiration. This case underscores the importance of
      considering germ cell tumors in the differential diagnosis of an unexplained
      retroperitoneal mass, particularly since immunophenotypic staining may be
      necessary to establish the diagnosis.

PMID- 21191537
TI  - Cancer and age related colonic crypt deficiencies in cytochrome c oxidase I.
AB  - AIM: To investigate whether deficiency of expression of cytochrome c oxidase I
      (CcOI) in colonic crypts is associated with colon cancer. METHODS: The pattern
      and level of expression of CcOI in non-neoplastic colonic crypts, and in
      dysplastic tissues, was assessed using standard immunohistochemical methods.
      Biopsies were obtained from individuals undergoing colonoscopies for screening
      purposes or for a medically indicated reason. Tissue samples were also obtained
      from surgical colonic resections. Samples from resections were taken from colonic
      mucosa 1 and 10 cm from tumors and from the tumors themselves. Samples were
      evaluated for frequency of crypts with reduced or absent expression of CcOI. In
      most crypts the loss was apparent throughout the entire crypt, while in a small
      minority the loss was segmental. The strong immunoreactivity using this
      monoclonal antibody makes the scoring unambiguous. The percent of crypts with
      reduced or absent expression of CcOI or (infrequent) segmented loss of expression
      was then calculated. Data analyses were performed using SPSS statistical package
      17.0. RESULTS: The average frequency of CcOI deficient crypts (CcOI-DC) is low in
      individuals between 20 and 39 years of age, with 0.48% +/- 0.40% CcOI-DC for
      women and 1.80% +/- 0.35% for men. CcOI-DC increases after age 40 years, so that
      between the ages of 40 and 44 years the average frequency of CcOI-DC goes up to
      5.89% +/- 0.84% in women and 2.15% +/- 1.27% in men. By 80-84 years of age, the
      average frequency of CcOI-DC goes up in women to 15.77% +/- 0.97% and in men to
      22.6% +/- 0.65%. The increases in CcOI-DC from ages 40-44 years compared to 80-84
      years in women and men are significantly different with P < 0.01. For women over
      age 60 years, deficiency of CcOI expression is greater in those women who have
      had a cancer in their colon. The frequency of CcOI-DC, measured in men, increased
      in tissues adjacent to colon cancer, being 4.03% +/- 0.27% in individuals free of
      neoplasia in the age range 55-64 years and 14.13% +/- 0.35% in resected
      histologically normal tissue of men with cancer in the same age range, P < 0.001.
      Similar significant differences were noted in older age ranges. The frequency of
      CcOI-DC crypts in the cecum and sigmoid colon of an individual are significantly
      correlated, with an R(2) = 0.414 for women and R(2) = 0.528 for men, P < 0.001.
      This suggests that the factors determining the level of CcOI deficiency act
      throughout the colon. Most defective crypts are in clusters of two or more, a
      likely consequence of crypt fission. In the non-neoplastic margins of cancers,
      crypts are frequently deficient for CcOI, and such crypts may appear in large
      clusters, some containing more than 100 deficient crypts. CcOI deficiency is also
      apparent in colon cancers and sometimes involves a large section of the tumor.
      Overall, CcOI deficient cells can be visualized in segments of crypts, in whole
      crypts that increase in frequency with age, in crypts undergoing fission, in
      clusters of crypts where the clusters increase in size with age, in increased
      frequency near tumors, in large clusters in the intimate margins of tumors, and
      in the tumors themselves. There is no clear dividing line between early stages
      that can be considered aspects of aging and later stages that can be considered
      aspects of the progression to cancer. This ambiguity may reflect a rather general
      situation leading to adult cancer where the early stages of cellular change
      appear to be relatively innocuous features of the aging process but over decades
      may evolve into malignancy. CONCLUSION: CcOI deficient crypts increase in
      frequency with age, and clusters of deficient crypts are associated with, and may
      give rise to, colon cancer.

PMID- 21191539
TI  - A rare case of anal tumor: Anal carcinosarcoma.
AB  - Sarcomatoid carcinoma is a rare tumor with a poor prognosis, otherwise known as
      carcinosarcoma. Gastrointestinal origin is very rare and only a limited number of
      anal carcinosarcomas have been reported in the literature. The management of this
      rare cancer type is controversial. The aim of this case report was to confirm
      that by combining treatment modalities we can achieve long disease free
      intervals. Concomitant chemoradiotherapy led to a good partial response and this
      was followed by a consolidation surgical endo-anal excision.

PMID- 21191540
TI  - Acute and recurring pericarditis: More colchicine, less corticosteroids.
AB  - Acute and recurring pericarditis are frequently encountered clinical entities.
      Given that severe complications such as tamponade and constrictive pericarditis
      occur rarely, the majority of patients suffering from acute pericarditis will
      have a benign clinical course. However, pericarditis recurrence, with its painful
      symptoms, is frequent. In effect, recent studies have demonstrated a beneficial
      role of colchicine in preventing recurrence, while also suggesting an increase in
      recurrences with the use of corticosteroids, the traditional first-line agent.

PMID- 21191541
TI  - Inflammation and reactive oxygen species in cardiovascular disease.
AB  - Reactive oxygen species (ROS) have long been proposed to be mediators of
      experimental cardiovascular pathology. There is also a wealth of data indicating
      that ROS are involved in clinical cardiovascular pathology. However, multiple
      clinical studies have shown little benefit from anti-oxidant treatments, whereas
      nearly all experimental studies have shown a marked effect of anti-oxidant
      therapy. One reason for this discrepancy is that ROS are produced through
      multiple different mechanisms of which some are clinically beneficial; thus, in a
      defined experimental system where predominately pathological ROS are generated
      does not mimic a clinical setting where there are likely to be multiple ROS
      generating systems producing beneficial and pathological ROS. Simple inhibition
      of ROS would not be expected to have the same result in these two situations;
      ergo, it is important to understand the molecular mechanism underlying the
      production of ROS so that clinical treatments can be tailored to target the
      pathological production of ROS. One such example of this in cardiovascular
      biology is tissue specific inflammation-mediated ROS generation. This and the
      following series of articles discuss the current understanding of the role of ROS
      in cardiovascular disease, specifically focusing on the molecular mechanisms of
      ROS generation and the actions of ROS within the cardiovascular system. Although
      there are still many areas with regard to the effects of ROS in the
      cardiovascular system that are not completely understood, there is a wealth of
      data suggesting that blocking pathological ROS production is likely to have
      beneficial clinical effects compared to traditional anti-oxidants.

PMID- 21191542
TI  - Endothelial progenitor cells as factors in neovascularization and endothelial
      repair.
AB  - Endothelial progenitor cells (EPCs) are a heterogeneous population of cells that
      are provided by the bone marrow and other adult tissue in both animals and
      humans. They express both hematopoietic and endothelial surface markers, which
      challenge the classic dogma that the presumed differentiation of cells into
      angioblasts and subsequent endothelial and vascular differentiation occurred
      exclusively in embryonic development. This breakthrough stimulated research to
      understand the mechanism(s) underlying their physiologic function to allow
      development of new therapeutic options. One focus has been on their ability to
      form new vessels in injured tissues, and another has been on their ability to
      repair endothelial damage and restore both monolayer integrity and endothelial
      function in denuded vessels. Moreover, measures of their density have been shown
      to be a better predictor of cardiovascular events, both in healthy and coronary
      artery disease populations than the classical tools used in the clinic to
      evaluate the risk stratification. In the present paper we review the effects of
      EPCs on revascularization and endothelial repair in animal models and human
      studies, in an attempt to better understand their function, which may lead to
      potential advancement in clinical management.

PMID- 21191543
TI  - Corruption of coronary collateral growth in metabolic syndrome: Role of oxidative
      stress.
AB  - The myocardium adapts to ischemic insults in a variety of ways. One adaptation is
      the phenomenon of acute preconditioning, which can greatly ameliorate ischemic
      damage. However, this effect wanes within a few hours and does not confer chronic
      protection. A more chronic adaptation is the so-called second window of
      preconditioning, which enables protection for a few days. The most potent
      adaptation invoked by the myocardium to minimize the effects of ischemia is the
      growth of blood vessels in the heart, angiogenesis and arteriogenesis (collateral
      growth), which prevent the development of ischemia by enabling flow to a
      jeopardized region of the heart. This brief review examines the mechanisms
      underlying angiogenesis and arteriogenesis in the heart. The concept of a redox
      window, which is an optimal redox state for vascular growth, is discussed along
      with signaling mechanisms invoked by reactive oxygen species that are stimulated
      during ischemia-reperfusion. Finally, the review discusses of some of the
      pathologies, especially the metabolic syndrome, that negatively affect collateral
      growth through the corruption of redox signaling processes.

PMID- 21191544
TI  - Role of genomics in cardiovascular medicine.
AB  - As all branches of science grow and new experimental techniques become readily
      accessible, our knowledge of medicine is likely to increase exponentially in the
      coming years. Recently developed technologies have revolutionized our analytical
      capacities, leading to vast knowledge of many genes or genomic regions involved
      in the pathogenesis of congenital heart diseases, which are often associated with
      other genetic syndromes, coronary artery disease and non-ischemic
      cardiomyopathies and channelopathies. The knowledge-base of the genesis of
      cardiovascular diseases is likely going to be further revolutionized in this new
      era of genomic medicine. Here, we review the advances that have been made over
      the last several years in this field and discuss different genetic mechanisms
      that have been shown to underlie a variety of cardiovascular diseases.

PMID- 21191545
TI  - Ergonovine stress echocardiography: Recent experience and safety in our centre.
AB  - AIM: To study recent experience and safety of ergonovine stress echocardiography
      in our centre. METHODS: In this study we collected the clinical variables of
      patients referred since 2002 for ergonovine stress echocardiography, in addition
      to indications, the results of this test, complications, blood pressure and heart
      rate values during the test and the number and results of tests requested before
      this technique. RESULTS: We performed 40 tests in 38 patients, 2 tests were
      carried out to verify therapy efficacy. The prevalence of classic cardiovascular
      risk factors was low and the most frequent indication was chest pain (57.5%).
      Coronary angiography was performed in 32 patients, and showed normal coronary
      arteries in 27 patients and non-significant stenosis in 5 cases. In 16 patients,
      coronary angiography was carried out after a positive or inconclusive ischemia
      test. Another 6 patients had a normal stress test (5 exercise electrocardiography
      tests and 1 nuclear imaging test). Of the 40 ergonovine stress echocardiography
      tests, 6 were positive (4 in the right coronary artery territory and 2 in the
      circumflex coronary artery territory), all of them by echocardiographic criteria,
      and by electrocardiographic criteria in only 3 (50%). The presence of non
      significant coronary artery stenosis was more frequent in patients with positive
      ergonovine stress echocardiography (50% vs 6%, P = 0.038), and were related to
      ischemic territory. During the maximum stress stage, there was a higher systolic
      (130.26 +/- 19.17 mmHg vs 136.58 +/- 27.27 mmHg, 95% CI: -12.77 to 0.14 mmHg, P =
      0.055) and diastolic blood pressure (77.89 +/- 13.49 mmHg vs 83.95 +/- 15.73
      mmHg, 95% CI: -10.41 to -1.69 mmHg, P = 0.008) than at the baseline stage, and
      the same was registered with heart rate (73 +/- 10.96 beats/min vs 79.79 +/-
      11.72 beats/min, 95% CI: -9.46 to -4.11 beats/min, P < 0.01). Nevertheless, there
      were only 2 hypertensive reactions during the last stage, which did not force a
      premature end to the test, without sustained tachy or bradyarrhythmias, and the
      technique was well tolerated in 58% of cases. A unique complication (2.5%) of
      this test was a prolonged vasospasm with a slight increase in necrosis
      biomarkers, however, this was without repercussion. CONCLUSION: Ergonovine stress
      echocardiography can be performed with safety, is well tolerated in the majority
      of cases, and is useful for determining the ischemia mechanism in selected cases.

PMID- 21191546
TI  - Spotlight on plagiarism.

PMID- 21191547
TI  - End organ damage in hypertension.
AB  - BACKGROUND: End organ damage in hypertension can be detected early, reflects
      accurately the hypertensive patient's overall cardiovascular risk, and should be
      prevented and treated with antihypertensive treatment. METHOD: We selectively
      review the relevant literature since 1995, including the German and European
      guidelines for the diagnosis and treatment of arterial hypertension. RESULTS:
      Measurement of the intima-media thickness in the common carotid artery and of the
      pulse-wave velocity is now recommended for the early diagnosis of hypertensive
      vasculopathy. Left ventricular hypertrophy, an important component of
      hypertensive heart disease, can be diagnosed by echocardiography and with the aid
      of new electrocardiographic indices. Early signs of hypertensive nephropathy,
      namely albuminuria and a decreased glomerular filtration rate, are prognostically
      valuable and easy to detect. Cerebrovascular damage, including early
      microangiopathic changes, is best diagnosed by magnetic resonance imaging. The
      treatment of end organ damage due to hypertension centers on blood pressure
      reduction. Blockade of the renin angiotensin-aldosterone system is an essential
      part of the treatment of early end organ damage. CONCLUSION: Hypertensive end
      organ damage can now be diagnosed early and reversed with specific and aggressive
      treatment.

PMID- 21191548
TI  - Recurrent tonsillitis in adults: quality of life after tonsillectomy. Not a
      trivial procedure.

PMID- 21191550
TI  - Idiopathic scoliosis.
AB  - BACKGROUND: Scoliosis is a three-dimensional deviation of the spinal axis. The
      main diagnostic criterion is spinal curvature exceeding 10 degrees  on a plain
      anteroposterior X-ray image. Scoliosis is called idiopathic when no other
      underlying disease can be identified. METHODS: Selective literature review and
      recommendations of the relevant medical societies in Germany and abroad. RESULTS:
      Scoliosis in children of school age and above primarily occurs in girls. Its
      prevalence is 1% to 2% among adolescents, but more than 50% among persons over
      age 60. The therapeutic goal in children is to prevent progression. In children,
      scoliosis of 20 degrees  or more should be treated with a brace, and scoliosis of
      45 degrees  or more with surgery. The treatment of adults with scoliosis is
      determined on an individual basis, with physiotherapy and braces playing a
      relatively minor role. Adults (even elderly adults) who have scoliosis and
      sagittal imbalance may be best served by surgical treatment. CONCLUSION:
      Scoliosis is common. Early diagnosis makes a major difference in the choice of
      treatment.

PMID- 21191551
TI  - Unbiased Invariant Least Squares Estimation in A Generalized Growth Curve Model.
AB  - This paper is concerned with a generalized growth curve model. We derive the
      unbiased invariant least squares estimators of the linear functions of variance
      covariance matrix of disturbances. Under the minimum variance criterion, we
      obtain the necessary and sufficient conditions of the proposed estimators to be
      optimal. Simulation studies show that the proposed estimators perform well.

PMID- 21191552
TI  - Compositional changes in neurotoxins and their oxidative derivatives from the
      dinoflagellate, Karenia brevis, in seawater and marine aerosol.
AB  - The harmful alga, Karenia brevis, produces a suite of polyether neurotoxins,
      brevetoxins or PbTx, that cause marine animal mortality and neurotoxic shellfish
      poisoning (NSP). A characteristic of K. brevis blooms is associated airborne
      toxins that result in severe respiratory problems. This study was undertaken to
      determine the composition of aerosolized brevetoxins and oxidative derivatives to
      which beachgoers are exposed during a K. brevis bloom. The suite of brevetoxins
      and derivatives in seawater is comprised of intra-cellular (IC) and extra
      cellular (EC) compounds. We hypothesized that aerosolized compounds are generated
      primarily from EC, hydrophobic compounds in seawater by bubble-mediated
      transport. Thus the composition of aerosolized brevetoxins and derivatives, to
      which beachgoers are exposed, would reflect the EC composition of the source
      matrix (the local surf zone). Brevetoxins were extracted from water collected
      along the shore and from marine aerosols along Siesta Beach and Lido Beach in
      Sarasota, FL, USA, during K. brevis blooms. Water samples were further processed
      into IC and EC components. The primary brevetoxins observed in water and air
      included PbTx-1, -2, -3, -PbTx-2-carboxylic acid, and brevenal. Oxidation and/or
      hydrolysis products of PbTx-1, -2, -3 and -7 were also found in EC water and in
      aerosol, but not IC.

PMID- 21191553
TI  - [Nosocomial candidemia: new challenges of an emergent problem].
AB  - Candida spp. are currently one of the most common causes of bloodstream
      infections in hospitals. Over the last two decades there has been a shift towards
      a greater involvement of non-Candida albicans as the cause of candidemia. Several
      of these non-albicans spp. (e.g., C. glabrata and C. krusei) exhibit resistance
      to traditional triazole antifungals (fluconazole), and cross-resistance with
      newer triazoles (voriconazole), focusing attention on the first-line use of
      antifungals such as the echinocandins, which possess improved activity against
      fluconazole-resistant strains. Early and adequate empirical treatment as well as
      early removing of the central catheters are the main factors related to
      mortality; thus it is necessary to implement guidelines of empirical treatment
      (including these aspects) in patients with risk factors and possible candidemia.
      Recent treatment guidelines from the Infectious Diseases Society of America
      (IDSA) recommend an echinocandin as primary therapy for non neutropenic or
      neutropenic patients with moderately severe to severe candidiasis and for
      patients at risk for infection with a triazole-resistant strain; the increasing
      MIC of echinocandins in case of C. parapsilosisis also an emerging concern.
      Clinicians should remain vigilant to prescribe early empiric treatment of
      patients at risk of having candidemia.

PMID- 21191554
TI  - [Antifungal agents in the treatment of systemic infections: Relevance of
      mechanism of action, activity profile and resistances].
AB  - The availability of different therapeutic alternatives has modified the treatment
      of systemic fungal infections. There commendations of antifungal therapy vary
      according to species which causes the mycosis and its susceptibility.
      Consequently, the knowledge of action mechanism, activity profile and resistances
      to antifungal agents are essential for the clinical practice. Amphotericin B is
      the antifungal agent exhibiting the broadest spectrum of activity, it is a
      fungicidal drug and resistances have been hardly ever described. The triazoles
      compounds also have a broad spectrum, but their massive use for some therapeutic
      indications has led to emergence of strains and species of yeasts with resistance
      to fluconazole and of filamentous fungi itraconazole resistant. The echinocandins
      exhibit fungicidal effects for yeasts andafungistatic activity against moulds,
      and secondary resistance to these agents is uncommon.

PMID- 21191555
TI  - [Prophylaxis and treatment of invasive fungal infection in neutropenic patients].
AB  - Prophylaxis and treatment constitute the basis for reducing the mortality due to
      IFI. Prophylaxis is currently the standard practice in most hospitals and is
      recommended by the principal guidelines. Fluconazole has proved to be useful to
      prevent and reduce the mortality due to yeast IFI in several contexts. Although
      its use has led to the emergence of some resistant strains of Candida, it has not
      been a generalized problem and the number of lives saved has been worth it. But
      its major disadvantage is the lack of impact on IFI by molds. So, in patients at
      high risk for IFI due to filamentous fungi, it is necessary the employ of
      extended spectrum drugs. For the empirical and preemptive approach, it is
      necessary to have in mind which fungi have to be covered and the spectrum of the
      available antifungal agents. For the treatment of established infection by
      Candida spp., before the identification of species, we must consider different
      host (like the use or not of prophylactic fluconazole) and clinical factors (like
      the evidence or not of diseminated infection or severe sepsis). Primary
      combination of antifungal agents for the treatment of invasive aspergillosis has
      to be considered in cases of central nervous system disease, respiratory failure,
      serious sepsis, and extensive or cavitated pulmonary lesions.

PMID- 21191556
TI  - [Experience of micafungin in patients requiring extrarenal depuration].
AB  - INTRODUCTION: The use of extrarenal depuration techniques is increasingly
      frequent in patients admitted to the ICU. The use of these procedures has been
      related to a decrease in plasma concentrations of several antimicrobials, among
      which fluconazole. The activity of antifungal agents depends on achievement on
      adequate concentrations in plasma and at the site of infection. Micafungin is a
      new antifungal drug recently introduced in our country. OBJECTIVE: To review the
      published experience of pharmacokinetic (PK) parameters of micafungin in patients
      requiring some type of extrarenal depuration procedures during their stay in the
      ICU. RESULTS: Three studies with data on PK parameters of micafungin during the
      use of this drug in continuous venovenous hemodialysis (2 publications) and
      continuous hemodiafiltration (1 publication) were retrieved. In all of them,
      minimal variations in the plasma concentration of micafungin at the entry and
      exit sites of the hemofilter and a negligible or minimal presence of micafungin
      in the ultrafiltration fluid were demonstrated. CONCLUSIONS: Adjustment of the
      doses or the interval between doses of micafungin during the use of extrarenal
      depuration techniques in critically ill patients admitted to the ICU is not
      necessary.

PMID- 21191557
TI  - Significance of lower respiratory tract cultures yielding Aspergillus spp. growth
      in a hospital without transplant patients.
AB  - INTRODUCTION: Isolation of Aspergillus spp. in non-neutropenic, non-transplant
      patients with chronic obstructive pulmonary disease (COPD) usually treated with
      corticosteroids is not easily interpretable. A retrospective review of clinical
      records corresponding to cultures (respiratory samples) yielding Aspergillus spp.
      in non- transplant patients was carried out. METHODS: Patients were assigned to
      four categories: colonization, possible, probable or definitive aspergillosis. A
      logistic regression model (step-wise procedure) was performed using as dependent
      variable mortality, and as independent variables those showing differences
      (p<=0.1) in the bivariant analysis. RESULTS: Sixty-nine patients were identified.
      Most were elderly (68.1% >=65 years), male (73.9%), presented comorbidities
      (84.1% Charlson index >=3), COPD (76.8%), were receiving high corticosteroid
      doses (66.7%), and had previously received antibiotics (94.2%). Forty-five cases
      were colonizations, 4 possible, 15 probable and 5 definitive aspergillosis. A.
      fumigatus was isolated in 75.4% patients: 66.7% colonized, 75% possible, 93.3%
      probable and 100% definitive aspergillosis. Colonized patients were older (71.9
      +/- 11.9 vs. 65.1 +/- 9.2 years; p= 0.018) and presented higher (p=0.034)
      comorbidity index than patients with aspergillosis. Mortality was 31.1% in
      colonized vs. 62.5% in aspergillosis (p=0.012). CONCLUSION: The isolation of A.
      fumigatus was associated with an increased probability of aspergillosis, with
      statistical association in the multivariate analysis between mortality and
      variables related to chemotherapy (no antifungal treatment), disease (diagnostic
      category) and immunity (leukocytosis).

PMID- 21191558
TI  - [Antibiotic susceptibility of Corynebacterium macginleyi strains causing
      conjunctivitis].
AB  - INTRODUCTION: Lipophilic corynebacteria are part of the saprophytic skin flora
      and they rarely cause infection. C. macginleyi is an exception since it has been
      involved in conjunctivitis and other ocular surface affections. MATERIAL AND
      METHODS: Thirty three C. macginleyi strains were obtained from conjunctival swabs
      from patients with conjunctivitis symptoms. The minimum inhibitory concentration
      (MIC) for 7 antibiotics (penicillin, gentamycin, ciprofloxacin, tetracycline,
      vancomycin, rifampicin and linezolid) was tested by broth microdilution method.
      RESULTS: One strain was resistant to ciprofloxacin (MIC=16 mg/L) and two were
      resistant to tetracycline (MIC= 64 y 16 mg/L). The rest of the strains were
      susceptible to all the antibiotics tested. CONCLUSIONS: At the moment, C.
      macginleyi does not present a major problem due to the low resistance rates shown
      in the present and other studies. However, epidemiological surveillance of its
      susceptibility pattern is needed as well as an appropriate use of topical
      antibiotics in order to achieve a good infection control.

PMID- 21191559
TI  - [Impact of the consumption of ophthalmic topical antibiotics].
AB  - INTRODUCTION: The aim of the study was to value the impact of the consumption of
      the topical antibiotics used in ophthalmology and to lay the foundations for
      their prudent use. MATERIAL AND METHODS: A descriptive study about antibiotic use
      in Spain between 1st January 2004 and 31th December 2008 was carried out. Drugs
      used in the study had to follow the next criteria: topical administration and
      ophthalmic antibiotics only or in association. Data of the number of vials and
      nosocomial consumption were provided by Intercontinental Marketing Services (IMS)
      and Health National System, respectively. RESULTS: Nosocomial and community
      ophthalmologic antiinfectives in 2008 mean a cost of 4.9 and 24.4 millions of
      euros, respectively increasing a 5.5% respect to the previous year. Six millions
      of vials were used, 65% were antibiotics alone and 35% antibiotics in
      association. The most used ophthalmic antibiotics in monoterapy were the
      aminoglycosides (tobramycin and gentamicin), followed by the quinolones while the
      most used ophthalmic antibiotic in association were gramicidine plus neomycine
      plus polimixin B. CONCLUSIONS: The ophthalmic antiinfectives market, alone and in
      association, used in the nosocomial and community context means 30 millions of
      euros and shows an increase about 6%. Strict measures in the antibiotic use are
      not taken incount in the context of the ophthalmic topical antibiotics.

PMID- 21191560
TI  - [Rapid identification of Mycobacterium tuberculosis complex from broth cultures
      by immunochromatographic assay].
AB  - BACKGROUND: Recently, a simple and rapid commercial assay (BD MGIT TBc ID) has
      been developed using a monoclonal antibody anti-MPT64 for the differentiation of
      Mycobacterium tuberculosis complex from other mycobacteria by
      immunochromatography. METHODS: We evaluate in this work the clinical usefulness
      of the test for the identification of 51 strains of M. tuberculosis complex and
      24 strains of other mycobacteria belonging to 14 different species, compared with
      the method of hybridization with DNA probes. RESULTS: Immunochromatographic
      method performance was excellent, with sensitivity, specificity, positive and
      negative predictive values of 98, 100, 96.1, and 98.7%, respectively.
      CONCLUSIONS: These results indicate that immunochromatographic assay can be
      safely used for rapid identification of M. tuberculosis complex in combination
      with culture in liquid media. The test is extremely simple, provides results in
      just 15 minutes, requires no complex equipment or specialized personnel and may
      be a good alternative to molecular methods, especially in small laboratories.

PMID- 21191561
TI  - Case collection study of the safety of AmBisome in association with voriconazole
      in the treatment of patients with invasive fungal infection.

PMID- 21191562
TI  - [Abscess cellulitis by Streptococcus pneumoniae].

PMID- 21191563
TI  - [Clinical use of rapid assays for the detection of influenza An/H1N1].

PMID- 21191564
TI  - [Comparasion of two methods for recovery of Aeromonas spp. in feces from agar CIN
      (Cefsulodin-Irgasan-Novobiocin)].

PMID- 21191565
TI  - Interferon-gamma negatively regulates Th17-mediated immunopathology during mouse
      hepatitis virus infection.
AB  - Fulminant hepatitis can cause acute liver failure and death in both humans and
      mice. However, the cellular and molecular mechanisms underlying the acute disease
      are still not well understood. Here, we examine the role of Th17 response in the
      development of the acute hepatitis following infection with mouse hepatitis virus
      (MHV). We show that IL-17 levels in serum are rapidly elevated and positively
      correlated to liver damage and death of the mice. In IFN-gammaR(-/-) mice, Th17
      response is enhanced and the elevated IL-17 production contributes to severe
      liver damage as well as detrimental inflammation because neutralization of IL-17
      effectively suppresses inflammation and protects mice from liver injury. We
      further show that IFN-gamma facilitates antigen-induced apoptosis of Th17 cells
      and adoptive transferred IFN-gammaR(-/-), but not IFN-gammaR(+/+); CD4(+) T cells
      promotes an enhanced liver damage in wild-type mice. The results demonstrate an
      essential role of Th17 cells in MHV-induced immunopathology and the importance of
      IFN-gamma in maintaining immune balance between Th1 and Th17 responses during
      acute viral infection.

PMID- 21191566
TI  - Heart failure-associated anemia: bone marrow dysfunction and response to
      erythropoietin.
AB  - Heart failure (HF)-associated anemia is common and has a poor outcome. Because
      bone marrow (BM) dysfunction may contribute to HF-associated anemia, we first
      investigated mechanisms of BM dysfunction in an established model of HF, the
      transgenic REN2 rat, which is characterized by severe hypertrophy and ventricular
      dilatation and SD rats as controls. Secondly, we investigated whether stimulation
      of hematopoiesis with erythropoietin (EPO) could restore anemia and BM
      dysfunction. After sacrifice, erythropoietic precursors (BFU-E) were isolated
      from the BM and cultured for 10 days. BFU-E were quantified and transcript
      abundance of genes involved in erythropoiesis were assayed. Number of BFU-E were
      severely decreased in BM of REN2 rats compared to SD rats (50 +/- 6.2 vs. 6.4 +/-
      1.7, p < 0.01). EPO treatment increased hematocrit in the SD-EPO group (after 6
      weeks, 49 +/- 1 vs. 58 +/- 1%, p < 0.01); however, in the mildly anemic REN2
      rats, there was no effect (43 +/- 1 vs. 44 +/- 1%). This was paralleled by a 67%
      decrease in BFU-E in BM of REN2 rats compared to SD (p < 0.01). EPO significantly
      improved BFU-E in both SD and REN2 but could not restore this to control levels
      in the REN2 rats. Expression of several genes involved in differentiation (LMO2),
      mobilization (SDF-1), and iron incorporation (transferrin receptor) of the BM
      were differentially expressed in REN2 rats compared to SD rats, and EPO did not
      normalize this. Altogether, these results suggest that BM dysfunction is an
      important contributor to HF-associated anemia and that EPO is not an effective
      agent to treat HF-associated anemia.

PMID- 21191567
TI  - Stable isotopes provide new insights into vestimentiferan physiological ecology
      at Gulf of Mexico cold seeps.
AB  - On the otherwise low-biomass seafloor of the Gulf of Mexico (GoM) continental
      slope, natural oil and gas seeps are oases of local primary production that
      support lush animal communities. Hundreds of seep communities have been
      documented on the continental slope, and nutrition derived from seeps could be an
      important link in the overall GoM food web. Here, we present a uniquely large and
      cohesive data set of delta(13)C, delta(15)N, and delta(34)S compositions of the
      vestimentiferan tubeworms Escarpia laminata and Lamellibrachia sp. 1, which
      dominate biomass at GoM seeps and provide habitat for hundreds of other species.
      Our sampling design encompassed an entire region of the GoM lower slope, allowing
      us for the first time to assess spatial variability in isotope compositions and
      to robustly address long-standing hypotheses about how vestimentiferans acquire
      and cycle nutrients over their long lifespan (200+ years). Tissue delta(13)C
      values provided strong evidence that larger adult vestimentiferans use their
      buried roots to take up dissolved inorganic carbon from sediment pore water,
      while very small individuals use their plume to take up carbon dioxide from the
      seawater. delta(34)S values were extremely variable among individuals of the same
      species within one location (<1 m(2) area), indicating high variability in the
      inorganic sulfur pools on a very small spatial scale. This finding supports the
      hypothesis that vestimentiferans use their roots to cycle sulfate and sulfide
      between their symbionts and free-living consortia of sulfate-reducing archaea in
      the sediment. Finally, consistent differences in delta(15)N between two
      cooccurring vestimentiferan species provided the first strong evidence for
      partitioning of inorganic resources, which has significant implications for the
      ecology and evolution of this taxonomic group.

PMID- 21191568
TI  - Identification of several small main-effect QTLs and a large number of epistatic
      QTLs for drought tolerance related traits in groundnut (Arachis hypogaea L.).
AB  - Cultivated groundnut or peanut (Arachis hypogaea L.), an allotetraploid (2n = 4x
      = 40), is a self pollinated and widely grown crop in the semi-arid regions of the
      world. Improvement of drought tolerance is an important area of research for
      groundnut breeding programmes. Therefore, for the identification of candidate
      QTLs for drought tolerance, a comprehensive and refined genetic map containing
      191 SSR loci based on a single mapping population (TAG 24 x ICGV 86031),
      segregating for drought and surrogate traits was developed. Genotyping data and
      phenotyping data collected for more than ten drought related traits in 2-3
      seasons were analyzed in detail for identification of main effect QTLs (M-QTLs)
      and epistatic QTLs (E-QTLs) using QTL Cartographer, QTLNetwork and Genotype
      Matrix Mapping (GMM) programmes. A total of 105 M-QTLs with 3.48-33.36%
      phenotypic variation explained (PVE) were identified using QTL Cartographer,
      while only 65 M-QTLs with 1.3-15.01% PVE were identified using QTLNetwork. A
      total of 53 M-QTLs were such which were identified using both programmes. On the
      other hand, GMM identified 186 (8.54-44.72% PVE) and 63 (7.11-21.13% PVE), three
      and two loci interactions, whereas only 8 E-QTL interactions with 1.7-8.34% PVE
      were identified through QTLNetwork. Interestingly a number of co-localized QTLs
      controlling 2-9 traits were also identified. The identification of few major,
      many minor M-QTLs and QTL * QTL interactions during the present study confirmed
      the complex and quantitative nature of drought tolerance in groundnut. This study
      suggests deployment of modern approaches like marker-assisted recurrent selection
      or genomic selection instead of marker-assisted backcrossing approach for
      breeding for drought tolerance in groundnut.

PMID- 21191571
TI  - Solution to Cleopatra's cocktail challenge.

PMID- 21191569
TI  - Effects on enantiomeric drug disposition and open-field behavior after chronic
      treatment with venlafaxine in the P-glycoprotein knockout mice model.
AB  - RATIONALE: P-glycoprotein (P-gp) plays an important role in the efflux of drugs
      from the brain back into the bloodstream and can influence the pharmacokinetics
      and pharmacodynamics of drug molecules. To our knowledge, no studies have
      reported pharmacodynamic effects of any antidepressant drug in the P-gp knockout
      mice model. OBJECTIVE: The aim of this study was to investigate the enantiomeric
      venlafaxine and metabolite concentrations in serum and brain of abcb1ab-/- mice
      compared to wild-type mice upon chronic dosing, and to assess the effect of
      venlafaxine treatment on open-field behavior. METHODS: P-gp knockout and wild
      type mice received two daily intraperitoneal injections of venlafaxine (10 mg/kg)
      over ten consecutive days. Locomotor and rearing activities were assessed on days
      7 and 9. After 10 days, drug and metabolite concentrations in brain and serum
      were determined using an enantioselective LC/MS/MS method. RESULTS: The brain
      concentrations of venlafaxine and its three demethylated metabolites were two to
      four times higher in abcb1ab-/- mice compared to abcb1ab+/+ mice. The behavioral
      results indicated an impact on exploration-related behaviors in the open-field as
      center activity was increased, and rears were decreased by venlafaxine treatment.
      CONCLUSION: Our results show that P-gp at the blood-brain barrier plays an
      important role in limiting brain entry of the enantiomers of venlafaxine and its
      metabolites after chronic dosing. Taken together, the present pharmacokinetic and
      pharmacodynamic findings offer the possibility that the expression of P-gp in
      patients may be a contributing factor for limited treatment response.

PMID- 21191570
TI  - Self-administration of cocaine and remifentanil by monkeys: choice between single
      drugs and mixtures.
AB  - RATIONALE: Cocaine and opioids are often co-abused. As yet, however, there is no
      clear evidence that the drugs interact to make the mixture a more effective
      reinforcer. OBJECTIVE: The present study examined the relative reinforcing
      potency and maximum effectiveness of the cocaine-opioid combination in monkeys
      given a choice between cocaine-opioid mixtures and the single-component drugs.
      METHOD: Rhesus monkeys were allowed to choose between injections of cocaine (100
      MUg/kg/inj) and other doses of cocaine (10-560 MUg/kg/inj) or remifentanil (0.03
      3.0 MUg/kg/inj). A dose-addition model was used to select dose combinations for
      mixtures of cocaine and remifentanil predicted to be equivalent to 100 MUg/kg/inj
      of cocaine in reinforcing effect if the drugs were additive. The monkeys were
      then allowed to choose between (a) cocaine and mixtures predicted to be
      equivalent to 100 MUg/kg/inj of cocaine, (b) increasing doses of the mixtures and
      the single-component drugs, and (c) cocaine or remifentanil at doses that were in
      the highest safe range. RESULTS: Generally, monkeys preferred the mixtures over
      100 MUg/kg/inj of cocaine, evidence for superadditivity. However, preferences for
      the mixture ceased when relatively high doses of single-component drugs were
      offered as alternatives. When doses within the mixture were raised and offered
      with relatively high doses of the single drugs, there was no clear preference for
      either option. The highest dose of remifentanil was chosen over the highest dose
      of cocaine by all monkeys. CONCLUSION: The current results indicate that cocaine
      opioid combinations can be super-additive in terms of potency, but are not, at
      maximum, more effective than the single-component drugs.

PMID- 21191572
TI  - Analysis of polyethyleneoxide macromonomers by liquid chromatography along the
      critical adsorption line.
AB  - Polyoxyethylene macromonomers are analyzed by one-dimensional liquid
      chromatography under different conditions, depending on the required information.
      These samples may contain polyethylene glycol (PEG) and the corresponding
      di(meth)acrylate besides the desired mono(meth)acrylate. The molar mass
      distribution (MMD) of the PEG and the monoester can be obtained by liquid
      adsorption chromatography (LAC) on a reversed-phase column in acetone-water with
      a gradient from 10% to 20% acetone. The MMD of the diesters can be obtained with
      isocratic elution by liquid chromatography at critical conditions (LCCC) on a
      reversed-phase column in 31% acetone, or using size-exclusion conditions for PEG
      and LAC conditions for the end groups, which is the case in 40-55% acetone. The
      absolute amount of the series with different functionality can be obtained by
      LCCC in ternary mobile phases consisting of acetone, methanol, and water along
      the critical adsorption line. Under such conditions, all series elute as narrow
      peaks (regardless their MMD), which can easily be integrated and quantified.

PMID- 21191573
TI  - Vibratory noise to the fingertip enhances balance improvement associated with
      light touch.
AB  - Light touch of a fingertip on an external stable surface greatly improves the
      postural stability of standing subjects. The hypothesis of the present work was
      that a vibrating surface could increase the effectiveness of fingertip signaling
      to the central nervous system (e.g., by a stochastic resonance mechanism) and
      hence improve postural stability beyond that achieved by light touch. Subjects
      stood quietly over a force plate while touching with their right index fingertip
      a surface that could be either quiescent or randomly vibrated at two low-level
      noise intensities. The vibratory noise of the contact surface caused a
      significant decrease in postural sway, as assessed by center of pressure measures
      in both time and frequency domains. Complementary experiments were designed to
      test whether postural control improvements were associated with a stochastic
      resonance mechanism or whether attentional mechanisms could be contributing. A
      full curve relating body sway parameters and different levels of vibratory noise
      resulted in a U-like function, suggesting that the improvement in sway relied on
      a stochastic resonance mechanism. Additionally, no decrease in postural sway was
      observed when the vibrating contact surface was attached to the subject's body,
      suggesting that no attentional mechanisms were involved. These results indicate
      that sensory cues obtained from the fingertip need not necessarily be associated
      with static contact surfaces to cause improvement in postural stability. A low
      level noisy vibration applied to the contact surface could lead to a better
      performance of the postural control system.

PMID- 21191574
TI  - Localization and expression of prothrombin in rodent osteoclasts and long bones.
AB  - The serum protein prothrombin (PT) is proteolytically converted to thrombin
      during the coagulation cascade by the cell-associated prothrombinase complex. In
      vitro, RANKL-differentiated osteoclasts express tissue factor and coagulation
      factor Xa, which convert PT to thrombin (Karlstrom et al. Biochem Biophys Res
      Commun 394:593-599, 2010). The present study investigated the localization of PT
      in bone as well as the expression of PT mRNA in bone and osteoclasts. Herein,
      immunoblot analysis detected PT and smaller proteolytically cleaved fragments
      with sizes consistent with the action of prothrombinase in a protein fraction
      extracted with guanidine-HCl EDTA from mouse tibia. Light microscopic and
      ultrastructural immunohistochemistry demonstrated the presence of PT in the newly
      formed bone matrix of the metaphysis. Furthermore, fluorescent
      immunohistochemistry on metaphyseal trabecular bone showed that PT colocalized
      with MMP-9-expressing subepiphyseal osteoclasts, whereas cathepsin K-expressing
      osteoclasts were closely associated with PT of the bone matrix. RT-qPCR analysis
      revealed that PT mRNA was detected in tibia. Expression of PT mRNA in the tibia
      was 0.2% of the level in the liver. In addition, PT mRNA expression was increased
      by RANKL-induced differentiation of bone marrow macrophages to osteoclasts. The
      results demonstrate that PT is synthesized and proteolytically processed in bone.
      Furthermore, PT is present mainly in the newly formed bone matrix of the
      metaphyseal trabecular bone compartment in close association to osteoclasts. In
      addition, MMP-9-positive osteoclasts contain PT, and PT expression is increased
      during osteoclastogenesis.

PMID- 21191575
TI  - Interaction between acetaminophen and warfarin in adults receiving long-term oral
      anticoagulants: a randomized controlled trial.
AB  - PURPOSE: We investigated whether acetaminophen, given at 2 g/day and 3 g/day
      might potentiate the anticoagulant effect of warfarin. METHODS: Forty-five
      patients on stable warfarin therapy, enrolled in this prospective, randomized,
      parallel (three arms), placebo-controlled study, received a 10-day regimen of
      acetaminophen (2 g/day or 3 g/day) or placebo. RESULTS: The mean maximal INR
      increase was 0.70 +/- 0.49 and 0.67 +/- 0.62 in patients receiving acetaminophen
      at 2 g/day and 3 g/day, respectively (P=0.01 for the respective comparisons
      versus placebo). The INR increase became significant on day 3 and was
      independently and significantly predicted by a maximal decrease in factor II
      (R(2)=0.36, P<0.0001), factor VII (R (2)=0.46, P<0.0001) and a maximal increase
      in acetaminophen plasma concentrations (R(2)=0.563, P<0.0001). CONCLUSION:
      Acetaminophen, at 2 g/day or 3 g/day, enhanced the anticoagulant effect of
      warfarin in stable patients, thus requiring close INR monitoring in the clinical
      setting.

PMID- 21191576
TI  - Clinical significance of uric acid dihydrate in urinary stones.
AB  - Uric acid crystallizes as an anhydrous compound (UAA), a dihydrate (UAD) or a
      mixture of both. A monohydrate form is very rare. About 20% of uric acid stones
      contain a significant amount (>=20%) UAD. It is believed that UAD crystallizes
      under highly acidic conditions (urine pH <= 5.0). Up to now, metabolic data on
      patients with UAD stones have not been reported in the literature. One hundred
      and fifty patients with pure uric acid calculi were studied. Stone analysis was
      performed using X-ray diffraction. According to the stone analysis, they were
      divided in two groups: 1. UAD (>=20% UAD), 2. UAA (<20% UAD). In all patients the
      following parameters were examined: age, sex, number of recurrences, body mass
      index (BMI); blood: creatinine, uric acid, calcium, sodium, and potassium; urine:
      pH-profiles, volume, calcium, uric acid, citrate, ammonia, and urea. Group 1
      (>=20% UAD) consisted of 33 patients and group 2 (<20% UAD) of 117 patients.
      Between these groups, there was a significant difference concerning the number of
      recurrences, the urine volume, and the urinary excretion of calcium. Patients
      with >=20% dihydrate had a mean BMI of 31.6 +/- 7.5, a mean number of recurrences
      of 0.24 +/- 0.44, an urine volume of 2.6 +/- 0.8 l/24 h, and a calcium excretion
      of 4.5 +/- 2.2 mmol/24 h, whereas those with <20% dihydrate had BMI of 29.9 +/-
      5.0, 1.10 +/- 1.42 recurrences, urine volume of 2.3 +/- 1.2 l/24 h, and calcium
      excretion of 3.2 +/- 2.4 mmol/24 h. All the other parameters tested were not
      significantly different. For the first time, our study shows metabolic data in
      uric acid patients with a significant amount of UAD. The comparison between this
      group and those patients with <20% UAD revealed that the first group is less
      prone to develop recurrences. This is a relevant difference concerning the
      necessity of metaphylactic measures. We could not confirm in patients with
      dihydrate if the urinary pH is more acid than in those with insignificant amounts
      of dihydrate. The higher 24-h urine volume, the higher excretion of calcium, and
      the higher BMI in the UAD group may be of pathophysiological relevance and
      requires further attention.

PMID- 21191577
TI  - Quality assurance: using the exposure index and the deviation index to monitor
      radiation exposure for portable chest radiographs in neonates.
AB  - BACKGROUND: Many methods are used to track patient exposure during acquisition of
      plain film radiographs. A uniform international standard would aid this process.
      OBJECTIVE: To evaluate and describe a new, simple quality-assurance method for
      monitoring patient exposure. This method uses the "exposure index" and the
      "deviation index," recently developed by the International Electrotechnical
      Commission (IEC) and American Association of Physicists in Medicine (AAPM). The
      deviation index measures variation from an ideal target exposure index value. Our
      objective was to determine whether the exposure index and the deviation index can
      be used to monitor and control exposure drift over time. MATERIALS AND METHODS:
      Our Agfa workstation automatically keeps a record of the exposure index for every
      patient. The exposure index and deviation index were calculated on 1,884
      consecutive neonatal chest images. Exposure of a neonatal chest phantom was
      performed as a control. RESULTS: Acquisition of the exposure index and
      calculation of the deviation index was easily achieved. The weekly mean exposure
      index of the phantom and the patients was stable and showed <10% change during
      the study, indicating no exposure drift during the study period. CONCLUSION: The
      exposure index is an excellent tool to monitor the consistency of patient
      exposures. It does not indicate the exposure value used, but is an index to track
      compliance with a pre-determined target exposure.

PMID- 21191579
TI  - Thirty years of experience with alumina-on-alumina bearings in total hip
      arthroplasty.
AB  - Alumina-on-alumina bearings in total hip arthroplasty have been developed in an
      attempt to minimise debris and the occurrence of osteolytic lesions. The
      outstanding tribological properties of this bearing system are explained by low
      surface roughness, high hardness for major scratch resistance, and high
      wettability. Since the 1970s, technological improvements in the manufacturing
      process of alumina components together with a better understanding of Morse taper
      technology have provided a surgical grade material with high density, high purity
      and small grains. Published studies on the outcome of total hip arthroplasty
      performed with this new generation of implants showed high survivorship
      especially in young and active patients, with survival rates free of revision of
      90.8% to 97.4% at ten years. However, concern remains over ceramic liner fracture
      and squeaking, which has been noted recently with increasing prevalence. This
      review will discuss the current knowledge on the use of alumina-on-alumina
      bearings.

PMID- 21191580
TI  - Association between serum vitamin D deficiency and knee osteoarthritis.
AB  - BACKGROUND: Insufficient levels of serum 25-hydroxyvitamin D (25-OHD) influence
      the knee joint cartilage and lead to development and progression of knee
      osteoarthritis (OA). The purpose of this study was to determine the status of
      serum 25-OHD levels in patients with knee OA compared with controls. METHODS: A
      total of 148 patients with knee OA and 150 controls were studied. Serum 25-OHD
      was measured by the ELISA method and concentrations <20 ng/ml were considered as
      deficient levels. Mann-Whitney U test was used for comparisons of means and
      logistic regression analysis with calculation of odds ratio (OR) was applied to
      determine association. RESULTS: The mean ages of patients and controls were 60.2
      +/- 12.9 and 60.1 +/- 10.2 years, respectively (P = 0.23). In the entire
      population the mean serum 25-OHD in OA patients was not significantly lower than
      controls (P = 0.28), but in subgroup analysis the mean 25-OHD in OA patients aged
      <60 years was significantly lower than controls (23.8 +/- 18.8 vs. 34.5. +/- 29.6
      ng/ml, P = 0.01). In this age group knee OA was significantly associated with
      serum 25-OHD deficiency which remained significant after adjusting for age and
      sex (adjusted OR = 2.26, 95% CI 1.15-4.4, P = 0.018). A greater association was
      observed in patients aged < 55 years (OR = 2.63, 95% CI 1.16-5.95, P = 0.01);
      whereas the association between OA and serum 25-OHD deficiency in patients aged
      >=60 years did not reach a significant level. CONCLUSION: These findings indicate
      a significant association between serum 25-OHD deficiency and knee OA in patients
      aged < 60 years and suggest serum 25-OHD measurement in any patient with symptoms
      suggestive of knee OA particularly at the initial stage of disease.

PMID- 21191578
TI  - The phylogenetic origins of natural killer receptors and recognition:
      relationships, possibilities, and realities.
AB  - Natural killer (NK) cells affect a form of innate immunity that recognizes and
      eliminates cells that are infected with certain viruses or have undergone
      malignant transformation. In mammals, this recognition can be mediated through
      immunoglobulin- (Ig) and/or lectin-type NK receptors (NKRs). NKR genes in mammals
      range from minimally polymorphic single-copy genes to complex multigene families
      that exhibit high levels of haplotypic complexity and exhibit significant
      interspecific variation. Certain single-copy NKR genes that are present in one
      mammal are present as expanded multigene families in other mammals. These
      observations highlight NKRs as one of the most rapidly evolving eukaryotic gene
      families and likely reflect the influence of pathogens, especially viruses, on
      their evolution. Although well characterized in human and mice, cytotoxic cells
      that are functionally similar to NK cells have been identified in species ranging
      from birds to reptiles, amphibians and fish. Although numerous receptors have
      been identified in non-mammalian vertebrates that share structural relationships
      with mammalian NKRs, functionally defining these lower vertebrate molecules as
      NKRs is confounded by methodological and interpretive complexities. Nevertheless,
      several lines of evidence suggest that NK-type function or its equivalent has
      sustained a long evolutionary history throughout vertebrate species.

PMID- 21191581
TI  - Bidirectional barbed suture migration: a unique complication after intracuticular
      closure.

PMID- 21191582
TI  - Does carbon dioxide therapy really diminish localized adiposities? Experimental
      study with rats.
AB  - BACKGROUND: The probability of a positive effect of carbon dioxide (CO(2)) gas on
      the physiologic oxidative lipolytic process led to its use for localized
      adiposities. The authors considered that existing studies on CO(2) therapy were
      not sufficient to exhibit the efficiency of CO(2) therapy. The scientific basis
      for evaluating CO(2) therapy including standard dietary regimen, standard daily
      physical effort, and standard psychosocial stimuli was not clear. Despite this
      unclear situation, CO(2) therapy is extremely popular worldwide. The authors
      designed an experimental study using histomorphologic examination and the laser
      Doppler flow meter to monitor treated tissue in rats. They devised a controlled
      applicator device appropriate for gas injection of rats and compared biochemical
      effects between CO(2) and breathable air. METHODS: In this study, 28 female
      Wistar rats weighing 300 g were divided into five groups: sham group, acute
      effect of CO(2) group, acute effect of breathable air group, chronic effect of
      CO(2) group, and chronic effect of breathable air group. Gas was injected into
      the right groin of the rats via a specially designed device. RESULTS: The bulging
      disappeared after approximately 30 min in the CO(2) injection groups but
      continued for more than 48 h in breathable air injection groups. The blood flow
      and velocity in terms of changes in the signals observed using the laser-Doppler
      technique did not demonstrate a significant increase in the values of the gas
      injection groups compared with the sham group 1. A statistical difference in the
      number of adipocytes was found between the groups. CONCLUSION: The study findings
      demonstrated a statistically significant decrease in adipocyte diameters during
      both the early and late phases of the subjects injected with CO(2). With
      adipocyte volume defined as an achievement, CO(2) therapy was found to be more
      successful than air injection. Furthermore, compared with the control group, the
      decrease in adipocyte volume also was statistically significant in breathable air
      injected groups (groups 3 and 5). This result suggests that the mechanical
      effects of gas injection are more important than the metabolic effects.

PMID- 21191583
TI  - Is it possible to train surgeons for rural Africa? A report of a successful
      international program.
AB  - BACKGROUND: The critical shortage of surgeons and access to surgical care in
      Africa is increasingly being recognized as a global health crisis. Across Africa,
      there is only one surgeon for every 250,000 people and only one for every 2.5
      million of those living in rural areas. Surgical diseases are responsible for
      approximately 11.2% of the total global burden of disease. Even as the importance
      of treating surgical disease is being recognized, surgeons in sub-Saharan Africa
      are leaving rural areas and their countries altogether to practice in more
      desirable locations. METHODS: The Pan-African Academy of Christian Surgeons
      (PAACS) was formed in 1997 as a strategic response to this profound need for
      surgical manpower. It is training surgical residents through a 5-year American
      competency-based model. Trainees are required to be of African origin and a
      graduate of a recognized medical school. RESULTS: To date, PAACS has established
      six training programs in four countries. During the 2009-2010 academic year,
      there were 35 residents in training. A total of 18 general surgeons and one
      pediatric surgeon have been trained. Two more general surgeons are scheduled to
      finish training in 2011. Four graduates have gone on to subspecialty training,
      and the remaining graduates are practicing general surgery in rural and
      underserved urban centers in Angola, Guinea-Conakry, Ghana, Cameroon, Republic of
      Congo, Kenya, Ethiopia, and Madagascar. CONCLUSIONS: The PAACS has provided
      rigorous training for 18 African general surgeons, one of whom has also completed
      pediatric surgery training. To our knowledge, this is the only international
      rural-based surgical training program in Africa.

PMID- 21191584
TI  - Optimizing preoperative management of rectal cancer.

PMID- 21191585
TI  - Percutaneous selective embolectomy using a Fogarty Thru-Lumen Catheter for
      pancreas graft thrombosis: a case report.
AB  - A 57-year-old woman with a history of diabetes mellitus underwent simultaneous
      pancreas-kidney transplantation. The pancreaticoduodenal graft was implanted in
      the right iliac fossa. The donor's portal vein was anastomosed to the recipient's
      inferior vena cava (IVC). Seven days after the surgery, a thrombus was detected
      in the graft veins. Percutaneous thrombolysis was immediately performed; however,
      venous congestion was still present. We therefore attempted selective embolectomy
      using a Fogarty Thru-Lumen Catheter. Thrombi were directed from the graft veins
      toward the IVC and captured in the IVC filter with complete elimination of the
      thrombus without any major complications. We present our technique for the
      successful treatment of pancreas graft thrombosis within a short time period by
      percutaneous selective embolectomy using a Fogarty Thru-Lumen Catheter.

PMID- 21191586
TI  - Frequency-domain intravascular optical coherence tomography of the
      femoropopliteal artery.
AB  - PURPOSE: Optical coherence tomography (OCT) is a catheter-based imaging method
      that employs near-infrared light to produce high-resolution intravascular images.
      The authors report the safety and feasibility and illustrate common imaging
      findings of frequency-domain OCT (FD-OCT) imaging of the femoropopliteal artery
      in a series of 20 patients who underwent infrainguinal angioplasty. METHODS:
      After crossing the lesion of interest, OCT was performed with a dextrose saline
      flush technique with simultaneous obstructive manual groin compression. An
      automatic pullback FD-OCT device was employed (each scan acquiring 54 mm of
      vessel lumen in 271 consecutive frames). OCT images were acquired before and
      after balloon dilatation and following provisional stenting if necessary and were
      evaluated for baseline characteristics of plaque or in-stent restenosis (ISR),
      vessel wall trauma after angioplasty, presence of thrombus, stent apposition, and
      tissue prolapse. Imaging follow-up was not included in this study's protocol.
      RESULTS: Twenty-seven obstructive lesions (18 cases of de novo atherosclerosis
      and 9 of ISR) of the femoropopliteal artery were imaged and 148 acquisitions were
      analyzed in total. High-resolution intravascular OCT imaging with effective blood
      clearance was achieved in 93.9%. Failure was mainly attributed to preocclusive
      proximal lesions and/or collateral flow. Mixed features of lipid pool areas,
      calcium deposits, necrotic core, and fibrosis were identified in all of the
      imaged atherosclerotic lesions, whereas ISR was purely fibrotic. After balloon
      angioplasty, OCT identified extensive intimal tears in all cases and one case of
      severe dissection that biplane subtraction angiography failed to identify.
      CONCLUSIONS: Infrainguinal frequency-domain optical coherence tomography is safe
      and feasible and may provide intravascular high-resolution imaging of the
      femoropopliteal artery during infrainguinal angioplasty procedures.

PMID- 21191587
TI  - Irreversible electroporation in a Swine lung model.
AB  - PURPOSE: This study was designed to evaluate the safety and tissue effects of IRE
      in a swine lung model. METHODS: This study was approved by the institutional
      animal care committee. Nine anesthetized domestic swine underwent 15 percutaneous
      irreversible electroporation (IRE) lesion creations (6 with bipolar and 3 with 3
      4 monopolar electrodes) under fluoroscopic guidance and with pancuronium
      neuromuscular blockade and EKG gating. IRE electrodes were placed into the
      central and middle third of the right mid and lower lobes in all animals.
      Postprocedure PA and lateral chest radiographs were obtained to evaluate for
      pneumothorax. Three animals were sacrificed at 2 weeks and six at 4 weeks.
      Animals underwent high-resolution CT scanning and PA and lateral radiographs 1 h
      before sacrifice. The treated lungs were removed en bloc, perfused with formalin,
      and sectioned. Gross pathologic and microscopic changes after standard
      hematoxylin and eosin staining were analyzed within the areas of IRE lesion
      creation. RESULTS: No significant adverse events were identified. CT showed focal
      areas of spiculated high density ranging in greatest diameter from 1.1-2.2 cm. On
      gross inspection of the sectioned lung, focal areas of tan discoloration and
      increased density were palpated in the areas of IRE. Histological analysis
      revealed focal areas of diffuse alveolar damage with fibrosis and inflammatory
      infiltration that respected the boundaries of the interlobular septae. No
      pathological difference could be discerned between the 2- and 4-week time points.
      The bronchioles and blood vessels within the areas of IRE were intact and did not
      show signs of tissue injury. CONCLUSION: IRE creates focal areas of diffuse
      alveolar damage without creating damage to the bronchioles or blood vessels.
      Short-term safety in a swine model appears to be satisfactory.

PMID- 21191588
TI  - Technical solutions to ensure safe yttrium-90 radioembolization in patients with
      initial extrahepatic deposition of (99m)technetium-albumin macroaggregates.
AB  - PURPOSE: To evaluate the incidence of extrahepatic deposition of technetium-99m
      labeled albumin macroaggregates ((99m)Tc-MAA) after pretreatment angiography,
      before yttrium-90 radioembolizaton ((90)Y-RE), and to report on technical
      solutions that can be used to ensure safe delivery of (90)Y-microspheres in
      patients with initial extrahepatic deposition. MATERIALS AND METHODS: A
      retrospective analysis of 26 patients with primary and secondary liver
      malignancies, who were scheduled for treatment with (90)Y-RE in our institution
      in 2009, was performed. The angiograms and single-photon emission computed
      tomography images of all patients were reviewed by an interventional radiologist
      and a nuclear medicine physician, respectively, to identify and localize
      extrahepatic deposition of (99m)Tc-MAA when present. Subsequently, the technical
      solutions were used to successfully perform (90)Y-RE in these patients were
      evaluated and described. RESULTS: Extrahepatic deposition of (99m)Tc-MAA was
      observed in 8 of 26 patients (31%). In 7 of 8 patients, a second pretreatment
      angiography was performed to detect the cause of extrahepatic deposition. The
      technical solutions to enable safe (90)Y microspheres delivery included more
      distal placement of the microcatheter in the proper/right hepatic artery in 4 of
      7 (57%) patients; (super)selective catheterization of multiple segmental branches
      in 2 of 7 (29%); and additional coiling of a newly detected branch in the
      remaining patient (14%). This was confirmed by a second MAA procedure. (90)Y-RE
      was eventually performed in 25 of 26 (96%) patients. No procedure-related
      complications (<30 days) were observed. CONCLUSION: Extrahepatic deposition of
      (99m)Tc-MAA after pretreatment angiography did occur in 8 of 26 (31%) patients.
      The technical solutions as presented allowed safe (90)Y-RE delivery in 25 of 26
      (96%) patients.

PMID- 21191589
TI  - Endovascular treatment of late in-stent-graft dissection after thoracic
      endovascular aneurysm repair.
AB  - Complications after endovascular repair of thoracic aortic pathologies may be
      devastating. We report the case of endovascular treatment of late in-stent-graft
      dissection after thoracic endovascular aneurysm repair (TEVAR). A 25-year-old man
      was admitted to our hospital 2 years after endovascular treatment of
      posttraumatic aortic pseudoaneurysm using stent-graft implantation with an acute
      sudden onset of ischemia in both legs with absent femoral pulses, numbness, and
      renal functions deterioration. Multidetector computed tomography (MDCT)
      angiography showed an intimal flap in the distal part of the stent-graft with
      critical stenosis of the residual lumen. The patient was successfully treated
      with stent-graft implantation by way of percutaneous approach while under local
      anesthesia. The risk of this late complication after TEVAR should be considered
      during follow-up, especially in young patients with increased physical activity.
      Endovascular treatment can be the method of choice for these patients.

PMID- 21191591
TI  - Acetic acid sclerotherapy for treatment of a bile leak from an isolated bile duct
      after laparoscopic cholecystectomy.
AB  - Bile leak after laparoscopic cholecystectomy is not uncommon, and it mainly
      occurs from the cystic duct stump and can be easily treated by endoscopic
      techniques. However, treatment for leakage from an isolated bile duct can be
      troublesome. We report a successful case of acetic acid sclerotherapy for bile
      leak from an isolated bile duct after laparoscopic cholecystectomy.

PMID- 21191590
TI  - Chemoembolization decreases drop-off risk of hepatocellular carcinoma patients on
      the liver transplant list.
AB  - INTRODUCTION: The drop-off risk for patients awaiting liver transplantation for
      hepatocellular carcinoma (HCC) is 22%. Transplant liver availability is expected
      to worsen, resulting in longer waiting times and increased drop-off rates. Our
      aim was to determine whether chemoembolization can decrease this risk. PATIENTS
      AND METHODS: Eighty-seven consecutive HCC patients listed for liver transplant
      (Milan criteria) underwent statistical comparability adjustments using the
      propensity score (Wilcoxon, Fisher's, and chi-square tests). Forty-three
      nonchemoembolization patients and 22 chemoembolization patients were comparable
      for Child-Pugh and Model for End-Stage Liver Disease scores, tumor size and
      number, alpha fetoprotein (AFP) levels, and cause of cirrhosis. We calculated the
      risk of dropping off the transplant list by assigning a transplant time to those
      who dropped off (equal probability with patients who were on the list longer than
      the patient in question). The significance level was obtained by calculating the
      simulation distribution of the difference compared with the permutations of
      chemoembolization versus nonchemoembolization assignment of the patients. Kaplan
      Meier estimators (log-rank test) were used to determine survival rates. RESULTS:
      Median follow-up was 187 +/- 110 weeks (range 38 to 435, date of diagnosis). The
      chemoembolization group had an 80% drop-off risk decrease (15%
      nonchemoembolization versus 3% chemoembolization, p = 0.04). Although survival
      was better for the chemoembolization group, it did not reach statistical
      significance. Two-year survival for the nonchemoembolization and
      chemoembolization group was 57.3% +/- 7.1% and 76.0% +/- 7.9%, respectively (p =
      0.078). CONCLUSIONS: Chemoembolization appears to result in a significant
      decrease in the risk of dropping off liver transplant list for patients with HCC
      and results in a tendency toward longer survival.

PMID- 21191592
TI  - Radiological insertion of Denver peritoneovenous shunts for malignant refractory
      ascites: a retrospective multicenter study (JIVROSG-0809).
AB  - PURPOSE: Peritoneal venous shunts (PVSs) are widely used for palliating symptoms
      of refractory malignant ascites and are recognized as one of the practical
      methods. However, reliable clinical data are insufficient because most previous
      reports have been small studies from single centers. We conducted a
      retrospective, multicenter study to evaluate the safety and efficacy of
      radiologically placed PVSs in patients with malignant refractory ascites.
      METHODS: A total of 133 patients with malignant ascites refractory to medical
      therapies were evaluated for patient characteristics, technical success,
      efficacy, survival times, adverse events, and changes in laboratory data.
      RESULTS: PVSs were successfully placed in all patients and were effective (i.e.,
      improvement of ascites symptoms lasting 7 days or more) in 110 (82.7%). The
      median duration of symptom palliation was 26 days and median survival time was 41
      days. The most frequent adverse event was PVS dysfunction, which occurred in 60
      (45.1%) patients, among whom function was recovered with an additional minimally
      invasive procedure in 9. Abnormalities in coagulation (subclinical disseminated
      intravascular coagulation) occurred in 37 (27.8%) patients, although only 7
      (5.3%) developed clinical disseminated intravascular coagulation. Other major
      adverse events were gastrointestinal bleeding (9.8%), sepsis (3.8%), and acute
      heart failure (3.0%). PVS was least effective in patients with elevated serum
      creatinine, bloody ascites, or gynecologic tumor. CONCLUSIONS: Radiological PVS
      is a technically feasible and effective method for palliating the symptoms from
      refractory malignant ascites, but preoperative evaluation and monitoring the
      postprocedural complications are mandatory to preclude severe adverse events
      after PVS.

PMID- 21191593
TI  - Unilateral thyrovertebral trunk: report of a rare arterial variant.
AB  - Atypical origins of the vertebral and the inferior thyroid arteries are rare
      anatomical findings. We present the case of a right-sided thyrovertebral trunk
      observed in a 91-year-old female cadaver. In this extremely rare vascular
      variation both the vertebral and the inferior thyroid arteries jointly originated
      from the subclavian artery as its first branch by forming a short trunk. A
      thyrocervical trunk was absent resulting in anomalous origins of most subclavian
      branches. The vertebral artery travelled cranially entering the transverse
      foramen of the fifth cervical vertebrae. We furthermore discuss the clinical
      significance of this variation in the context of surgical and interventional
      procedures performed in the lateral neck region.

PMID- 21191594
TI  - A phase I pharmacokinetics study of 9-nitrocamptothecin in patients with advanced
      solid tumors.
AB  - PURPOSE: 9-Nitrocamptothecin (9-NC) is a novel orally administered camptothecin
      analog. The purpose of this study is to evaluate the pharmacokinetics and safety
      of 9-nitrocamptothecin in patients with advanced solid tumors. METHODS: The 23
      patients for a single-dose pharmacokinetic experiment were divided into 3 dosing
      cohorts. The dosage of 9-nitrocamptothecin capsule was 1.25, 1.5 and 1.75
      mg/m(2), respectively. The 8 patients for a multiple-dose pharmacokinetic study
      were orally administered 9-nitrocamptothecin 1.5 mg/m(2) for 5 consecutive days.
      Determination of the plasma concentration of 9-nitrocamptothecin was performed by
      high-performance liquid chromatography-ultraviolet detector technique, and
      determination of plasma concentration of 9-aminocamptothecin was performed by
      high-performance liquid chromatography-fluorescence detector technique. RESULTS:
      In the single-dose pharmacokinetic study, the mean +/- SD 9-nitrocamptothecin
      C(max) were 94.49 +/- 41.38, 115.56 +/- 63.27 and 147.57 +/- 38.19 ng/mL; AUC(0
      36) were 877.14 +/- 360.90, 961.33 +/- 403.58 and 1,189.75 +/- 405.80 ng h/mL,
      respectively; the mean +/- SD 9-aminocamptothecin C(max) were 12.85 +/- 6.46,
      10.72 +/- 6.58 and 28.74 +/- 31.94 ng/mL; AUC(0-36) were 157.61 +/- 111.61, 88.71
      +/- 39.51 and 173.52 +/- 122.19 ng h/mL, respectively. In the multiple-dose
      pharmacokinetic study, the mean +/- SD 9-nitrocamptothecin AUC(ss) was 907.04 +/-
      736.47 ng h/mL, C(max) was 85.98 +/- 47.52 ng/mL, C(min) was 18.91 +/- 22.50
      ng/mL, C(av) was 37.79 +/- 30.69 ng/mL, DF was 2.16 +/- 0.87; the mean +/- SD 9
      aminocamptothecin AUC(ss) was 442.73 +/- 308.39 ng h/mL, C(max) was 34.83 +/-
      18.31 ng/mL, C(min) was 10.32 +/- 6.95 ng/mL, C(av) was 18.45 +/- 12.85 ng/mL, DF
      was 1.34 +/- 0.42. Comparing single-dose 1.5 mg/m(2) group with multiple-dose 1.5
      mg/m(2) group, no significant difference was observed in 9-NC pharmacokinetic
      parameters, but with respect to the metabolite, significant differences were
      observed in C(max) and AUC. The toxicity of 9-NC varied from mild to moderate. No
      grade 3 or grade 4 toxicity was observed during the study. There was 2- to 13
      fold variabilities in 9-NC and 9-AC exposure among different patients for any
      given dose of 9-NC. CONCLUSIONS: All participants had good tolerance throughout
      the study. 9-NC and 9-AC exposure did not increase proportionally to the dose
      ranging from 1.25 to 1.75 mg/m(2). After 5-day continuous administration,
      accumulation was observed in the metabolite 9-AC, but not in 9-NC.

PMID- 21191595
TI  - Androgenesis in recalcitrant solanaceous crops.
AB  - Tomato, eggplant, and pepper are three solanaceous crops of outstanding
      importance worldwide. For hybrid seed production in these species, a fast and
      cheap method to obtain pure (homozygous) lines is a priority. Traditionally, pure
      lines are produced by classical inbreeding and selection techniques, which are
      time consuming (several years) and costly. Alternatively, it has become possible
      to accelerate the production of homozygous lines through a biotechnological
      approach: the induction of androgenesis to generate doubled haploid (homozygous)
      plants. This biotechnological in vitro tool reduces the process to only one
      generation, which implies important time and costs savings. These facts make
      androgenic doubled haploids the choice in a number of important crops where the
      methodology is well set up. Unfortunately, recalcitrant solanaceous crops such as
      tomato, eggplant, and pepper are still far from an efficient and reliable
      technology to be applied on a routine basis to different genotypes in breeding
      programs. In eggplant and pepper, only anther cultures are known to work
      relatively well. Unfortunately, a more efficient and promising technique, the
      culture of isolated microspores, is not sufficiently developed yet. In tomato,
      none of these methods is available nowadays. However, recent advances in the
      knowledge of embryo development are filling the gaps and opening new ways to
      achieve the final goal of an efficient protocol in these three recalcitrant
      species. In this review, we outline the state of the art on androgenic induction
      in tomato, eggplant, and pepper, and postulate new experimental ways in order to
      overcome current limitations.

PMID- 21191596
TI  - Genetic engineering of radish: current achievements and future goals.
AB  - Radish is a major root crop grown in the Far East and is especially important to
      some low-income countries where it is consumed on a daily basis. Developments in
      gene technology systems have helped to accelerate the production of useful
      germplasms, but progress has been slow, though achieved, via in planta methods
      and useful traits have been introduced. In the wake of the new Millennium, future
      goals in terms of improving transformation efficiency and selection of new traits
      for generating late-flowering radish are described. Furthermore, the techniques
      available for incorporating pharmaceutical proteins into radish to deliver edible
      proteins on-site are discussed. Finally, the concerns of releasing transgenic
      radish to the field in terms of pollen-mediated gene transfer are also reviewed.
      Such a report identifies key areas of research that is required to allow the crop
      satisfy the need of poor impoverished countries in the Far East.

PMID- 21191597
TI  - Should we abstain from Gleason score 2-4 in the diagnosis of prostate cancer?
      Results of a German multicentre study.
AB  - PURPOSE: The present study analysed the loss of prognostic information related to
      the abandonment of Gleason score (GS) 2-4 by the International Society of
      Urological Pathology (ISUP-2005). METHODS: Within a 10-year period prior to the
      modification of GS, 856 patients (mean age 64.2 years) underwent radical
      prostatectomy (RP). The grade of agreement between GS in biopsy and definitive
      histology was calculated by Kappa statistics (kappa). Univariable and
      multivariable influence of different preoperatively available parameters on
      disease-free survival (DFS) were assessed. The mean follow-up period was 39
      months. RESULTS: Concordance between GS in biopsy versus RP samples was 58%
      (kappa-value 0.354) and was improved by an increased number of biopsy cores.
      Undergrading in biopsy was present in 38% and not significantly enhanced by an
      extended time-period between biopsy and RP (threshold 90 d). PSA level, clinical
      tumour stage, fraction of positive cores (dichotomized at 34%), cases of RP per
      year and institution (dichotomized at 75), and GS independently influenced DFS.
      An upgrading to GS >= 7 was found in only 5.7% of patients presenting with GS 2-4
      in the biopsy. Independent from definitive histology, patients with GS 2-4 had a
      significantly better prognosis compared to patients with a higher GS.
      CONCLUSIONS: The present study shows an independent prognostic impact of GS in
      biopsy samples classified according to the previous classification. The
      elimination of GS 2-4 by the ISUP 2005 results in a considerable loss of
      pretherapeutic prognostic information and therefore should be questioned in
      particular with regard to the increasing demand for active surveillance regimens.

PMID- 21191598
TI  - 33% radius evaluation to assess bone mineral density in prostate cancer patients.
AB  - PURPOSE: Dual-energy X-ray absorptiometry (DXA) is the standard method to assess
      bone mineral density (BMD). The International Society for Clinical Densitometry
      recommends the measurement of BMD at lumbar spine, total hip and femoral neck,
      but in certain circumstances the 33% radius may be the recommended area to
      measure BMD. The aim of this study has been to analyze whether 33% radius should
      be considered the recommended area to assess BMD in prostate cancer patients.
      METHODS: This is a retrospective study where BMD was assessed by DXA at 33%
      radius, lumbar spine, total hip, and femoral neck (cDXA) in 141 prostate cancer
      patients. Twenty-eight patients were hormone naive while 113 were subjected to
      androgen suppression (AS) during the mean period of 29 months. Osteoporosis was
      diagnosed when T-score was lower than -2.5 and osteopenia when it ranged between 
      1 and -2.5. RESULTS: The osteoporosis rate was 29.8% at 33% radius, 23.4% at
      femoral neck, 19.9% at lumbar spine, and 12.8% at total hip. The overall
      osteoporosis rate at cDXA was 29.1%. Osteoporosis was detected in 52.2% at 33%
      radius and 36.2% at cDXA. Normal BMD was found in 17.7% at 33% radius and 34.8%
      at cDXA. The 33% radius was the only site where a significant increase in the
      osteoporosis rate was detected in patients subjected to AS compared to those
      hormone naive (33 and 13.8%). CONCLUSIONS: The 33% radius seems more sensible
      than the central skeleton areas to detect bone mass loss in patients with
      prostate cancer.

PMID- 21191599
TI  - High serum matrix metalloproteinase-3 and liver stiffness in postoperative
      biliary atresia.
AB  - BACKGROUND: Biliary atresia (BA) is a neonatal liver disorder characterized by
      chronic inflammation and obliteration of extrahepatic bile ducts. The purpose of
      the study was to investigate serum matrix metalloproteinase-3 (MMP-3) in
      postoperative BA patients and the association of MMP-3 with clinical outcome and
      liver stiffness score. METHODS: Fifty-eight BA patients post-Kasai operation and
      20 controls were enrolled. None of the patients had undergone liver
      transplantation. BA patients were classified into two groups according to their
      serum total bilirubin (TB) levels (TB < 2 mg/dL, no jaundice vs. TB >= 2 mg/dL,
      persistent jaundice) and alanine aminotransferase (ALT) levels (ALT < 45 IU/L,
      normal ALT vs. ALT >= 45 IU/L, elevated ALT). Serum MMP-3 levels were determined
      by enzyme-linked immunosorbent assay. Liver stiffness scores were measured by
      FibroScan. RESULTS: BA patients had greater MMP-3 levels (10.8 +/- 1.0 vs. 7.9 +/
      0.8 ng/mL, P = 0.02) and higher liver stiffness values than controls (29.7 +/-
      3.0 vs. 5.1 +/- 0.5 kPa, P < 0.001). Serum MMP-3 levels were significantly
      elevated in BA patients with jaundice when compared with those without jaundice
      (15.3 +/- 2.2 vs. 8.5 +/- 0.8 ng/mL, P = 0.004). In addition, BA patients with
      elevated ALT had higher levels of serum MMP-3 than those with normal ALT (12.4 +/
      1.5 vs. 8.3 +/- 0.9 ng/mL, P = 0.02). Moreover, BA patients with portal
      hypertension displayed higher serum MMP-3 than those without portal hypertension
      (13.5 +/- 1.5 vs. 7.4 +/- 0.8 ng/mL, P = 0.001). There was also a correlation
      between serum MMP-3 and liver stiffness scores (r = 0.448, P <= 0.001).
      CONCLUSION: Serum MMP-3 was associated with hepatic dysfunction and liver
      stiffness in postoperative BA patients. Accordingly, MMP-3 could play a role in
      the pathophysiology of hepatic fibrosis in BA after Kasai operation.

PMID- 21191600
TI  - Retroperitoneal air after percutaneous nerve evaluation for irritable bowel
      syndrome.

PMID- 21191601
TI  - Superficial neurofibromas in the setting of schwannomatosis: nosologic
      implications.
AB  - First described in the past decade, schwannomatosis is a syndrome distinct from
      neurofibromatosis 2 (NF2). It is characterized by the development of multiple
      schwannomas, sparing the vestibular division of cranial nerve VIII, and may also
      predispose to develop meningiomas. We report two female patients, a 27 and a 44
      years old who developed multiple peripheral schwannomas, but without involvement
      of the vestibular nerves, satisfying clinical criteria for schwannomatosis. Lack
      of vestibular nerve involvement was confirmed with MRI using an internal auditory
      canal protocol with 3 mm thick slices in both patients after age 30. Both
      patients developed a small neurofibroma in axillary subcutaneous tissues and a
      diffuse cutaneous neurofibroma of the left buttock, respectively. This report
      highlights that superficial neurofibromas may arise in the setting of
      schwannomatosis, which may have implications for the diagnostic criteria of this
      unique syndrome. In particular, the presence of a cutaneous neurofibroma in a
      patient with multiple schwannomas should not lead to a diagnosis of NF2.

PMID- 21191603
TI  - Mechanical stability analysis of reference clamp fixation in computer-assisted
      spine surgery.
AB  - BACKGROUND: Pedicle screw misplacement is a common complication, while 7% may
      result in neurological complications. Computer-assisted navigation improves the
      rate of ideally placed screws. Inappropriate reference marker attachment can
      cause major problems in the outcome and duration of surgery. OBJECTIVE: To
      improve fixation of reference bases by comparing different designs of spine
      clamps and measuring their stability against the relevant thoracic and lumbar
      anatomy. METHODS: Force needed to dislocate the clamp from the processus spinosus
      using defined fixation of 0.79, 0.90 and 1.02 Nm torque was evaluated. Force
      transmission from clamp to the processus spinosus was also examined. Artificial
      thoracic and lumbar vertebral bodies were used for attaching spine clamps of
      three different designs. An instrument transmitted linear force onto the
      reference clamp and recorded the force when dislocation occurred. Another device
      determined transmitted force for each clamp utilizing 0.79, 0.90, 1.02, 1.13 and
      1.24 Nm torque. RESULTS: L-clamp had the most stable fixation in lumbar section
      for every torque and developed the greatest forces. These transmitted forces were
      similar to the less stable Y-design. I-design created the smallest forces and had
      the most stable fixation for thoracic spine. The Y- and the L-design caused a
      notably high number of fractures. CONCLUSION: Great force leads to great
      stability, but also creates more fractures, favoring the use of smaller forces.
      Specific anatomy adaptation is important. Different clamp designs create
      different forces, while still differing in stability depending on their
      application in the thoracic or the lumbar spine.

PMID- 21191604
TI  - Anterior cervical multilevel decompression and fusion using fibular strut as
      revision surgery for failed cervical laminoplasty.
AB  - STUDY DESIGN: Retrospective analyses of six cases. OBJECTIVE: To describe six
      patients with previous failed laminoplasty who were subsequently managed by
      anterior cervical decompression and fusion (ACDF) using fibular strut as revision
      surgeries. SUMMARY OF BACKGROUND DATA: While several complications and
      unsatisfactory results of cervical laminoplasty have been reported, there is no
      general consensus on how to best surgically treat these pathological conditions.
      METHODS: Six patients, who had been treated by laminoplasty for cervical
      spondylotic myelopathy (n = 2) or ossification of posterior longitudinal ligament
      (OPLL, n = 4) and had unfavorable outcomes, underwent ACDF using autogenous
      fibular strut grafts. The pathological factors associated with the poor outcomes
      were intraforaminal spur, slip, spondylotic change, disc herniation, and increase
      of OPLL in size. Clinical outcomes were assessed by evaluating the modified
      Japanese Orthopedic Association score (JOA score) of cervical myelopathy,
      severity of radicular pains, axial pains, and perioperative complications. In
      addition, C2-7 angle and the presence of bony union were analyzed. RESULTS: The
      revision ACDF significantly increased the mean +/- SD. JOA score, from 10.3 +/-
      3.9 to 13.5 +/- 2.7 points (p = 0.028), with a recovery rate of 47.1 +/- 26.7%.
      Radicular pain and axial pain also improved. C2-7 angle was not changed
      significantly. Solid fusion was achieved in all patients at 12.2 +/- 4.2 months
      after revision surgery. CONCLUSION: ACDF with fibular strut graft was effective
      as a revision procedure for failed laminoplasty.

PMID- 21191602
TI  - Glutathione depletion and overproduction both initiate degeneration of nigral
      dopaminergic neurons.
AB  - Parkinson's disease is a neurodegenerative disorder characterized by severe motor
      deficits mainly due to degeneration of dopaminergic neurons in the substantia
      nigra. Decreased levels of the cell's most important anti-oxidant, glutathione,
      have been detected in nigral neurons of Parkinson patients, but it is unknown if
      they are the cause or merely the consequence of the disease. To elucidate if
      glutathione depletion causes selective degeneration of nigral dopaminergic
      neurons, we down-regulated glutathione synthesis in different brain areas of
      adult rats by a viral vector-based RNAi approach. Decreased glutathione synthesis
      resulted in progressive degeneration of nigral dopaminergic neurons, while extra
      nigral and striatal neurons were significantly less vulnerable. Degeneration of
      dopaminergic neurons was accompanied by progressive protein aggregate formation
      and functional motor deficits and was partially rescued by alpha-synuclein. That
      the survival of nigral dopaminergic neurons depends on the precise control of
      glutathione levels was further demonstrated by significant degeneration induced
      through moderate overproduction of glutathione. Over-expression of either of the
      two subunits of glutamate-cysteine ligase induced aberrant glutathiolation of
      cellular proteins and significant degeneration of dopaminergic neurons. Thus,
      while glutathione depletion was demonstrated to be a selective trigger for
      dopaminergic neuron degeneration, a glutathione replacement approach as a
      potential treatment option for Parkinson's patients must be considered with great
      care. In conclusion, our data demonstrate that survival of nigral dopaminergic
      neurons crucially depends on a tight regulation of their glutathione levels and
      that the depleted glutathione content detected in the brains of Parkinson's
      disease patients can be a causative insult for neuronal degeneration.

PMID- 21191605
TI  - Femoral malrotation following intramedullary nailing in bilateral femoral shaft
      fractures.
AB  - INTRODUCTION: This study was designed to evaluate the incidence of femoral
      malrotation in bilateral femoral shaft fractures. MATERIALS AND METHODS: All
      closed bilateral femoral shaft fractures in patients aged 18 or over treated
      between April 2000 and December 2009 were included in the current study. All
      patients received a postoperative CT-scan to estimate femoral antetorsion and leg
      length. All bilateral fractures were treated with intramedullary nailing on a
      radiolucent table. Retrospectively, all patients were analyzed according to the
      following parameters: (1) femoral antetorsion of both limbs and antetorsion
      difference in degrees, (2) femoral length discrepancy (cm), (3) incidence of
      femoral malrotation >15 degrees , (4) revision rate due to femoral malrotation.
      RESULTS: A total of 24 patients (11 [45.8%] female; 13 [52.8%] male) with
      bilateral femoral shaft fractures were included in this study of average age 38
      years (median 38 years, range 18-74 years). Clinically relevant malrotation
      (greater than 15 degrees ) was found in 10 cases (41.2%), whereas in 4 cases
      (40%) a revision surgery was required. DISCUSSION: Bilateral femoral shaft
      fractures are associated with a high incidence of clinically relevant femoral
      malrotation over 15 degrees . Measurement of intraoperative femoral antetorsion
      in bilateral femoral shaft fractures is quite difficult and currently only
      feasible postoperatively.

PMID- 21191606
TI  - Oxford Shoulder Score: cross-cultural adaptation and validation of the Turkish
      version.
AB  - BACKGROUND: The Oxford Shoulder Score (OSS) is a questionnaire developed to
      evaluate patients with certain shoulder problems. This study aimed to translate
      and culturally adapt a Turkish version of the OSS and validate its use for
      assessing Turkish patients with shoulder pathology. PATIENTS AND METHODS: OSS was
      translated and culturally adapted according to the guidelines in the literature.
      Eighty-four patients (mean age 49.26 +/- 11.92 years) with shoulder problems
      participated. Patients completed the Turkish OSS, the Short Form 36 (SF-36), and
      the Shoulder Pain and Disability Index (SPADI). Internal consistency was tested
      using Cronbach alpha coefficient. Reproducibility was assessed by asking patients
      to complete another OSS 48 h after the first test. Correlation between the total
      results of both tests was determined by the Pearson correlation coefficient and
      ICC. Validity was assessed by calculating the Pearson correlation coefficient
      between the OSS and SPADI and SF-36 scores. Floor and ceiling effects were
      analyzed. RESULTS: The internal consistency was high (Cronbach's alpha 0.92). The
      reproducibility tested by two different methods showed no significant difference.
      Correlation between the OSS and SPADI and SF-36 physical component summary score
      were -0.7, and 0.6, respectively (p < 0.001). There was no floor or ceiling
      effect in total OSS score. CONCLUSION: The Turkish version of the OSS proved to
      be valid, reliable and reproducible instrument as demonstrated by high Cronbach
      alpha and Pearson Correlation Coefficients. The application and evaluation of the
      instrument was feasible and minimally time consuming for use in clinical trials
      in Turkish-speaking patients with shoulder problems.

PMID- 21191607
TI  - Repeated percutaneous vertebroplasty for refracture of cemented vertebrae.
AB  - BACKGROUND: Percutaneous vertebroplasty is an efficient procedure to treat
      painful osteoporotic vertebral compression fractures. However, refracture of
      cemented vertebrae occurs rarely after percutaneous vertebroplasty. This study
      was undertaken to investigate the incidence, characteristics, predisposing
      factors, and mistakes in technique associated with refracture of the same
      vertebra after percutaneous vertebroplasty. METHODS: From 2001 to 2008, PVP with
      bone cement (polymethylmethacrylate, PMMA) was carried out in 2,291 patients with
      2,581 PVP procedures. The etiologies including pathologic fracture (including
      metastasis, osteolytic tumor, hemangioma) in 299 patients, infectious spondylitis
      in 4 patients and osteoporotic compression fractures in 1,988 patients. A total
      of 1,988 patients with 2,110 VCFs underwent PVP with PMMA cement after failing
      conservative treatment for at least 3 months. New recollapsed vertebral fractures
      were diagnosed as recurrent intractable back pain, postoperatively correlated
      with serial plain radiography and MR image. Clinical parameters such as age,
      gender, body mass index, and fracture-free interval (from the date of the initial
      intervention with percutaneous vertebroplasty to the diagnosis of subsequent
      fractures) were recorded. Parameters related to imaging and technical
      characteristics, including the amount of bone cement injected per procedure,
      level, the presence of osteonecrosis in the vertebral body, and the surgical
      approach (uni- or bipedicles), the restoration of kyphosis angle and height of
      the anterior border of the collapsed vertebral body, and any leakage of cement
      into the disk space were also recorded. RESULTS: In a 2-year follow-up, 1,800
      patients with 1,820 VCFs were retrospectively reviewed and 10 patients with 10
      VCFs developed refracture of the same vertebra after PVP with an incidence rate
      of 0.56% (10 in 1,800). The mean age of the ten patients (nine females and one
      male) was 79.6 years, and the mean BMI is 22.3. Levels of refracture after PVP
      were all located in the thoracolumbar junction (T12-L2): three in T12; four in
      L1; and three in L2. Osteonecrosis was present in all patients and intradiscal
      cement leakage was noted in five patients. The mean of the restoration of
      kyphosis angle was 7.7 degrees  and height of the anterior border was 26%.
      Osteonecrosis, greater anterior vertebral height restoration, lesser kyphosis
      angle correction and cystic filling pattern were statistically significant.
      CONCLUSIONS: Our study suggests that larger height restoration and solid lump
      filling cement are risk factors of refracture of cemented vertebral bodies.
      Symmetric cement distribution and fluid aspiration would be the potential ways to
      avoid refracture of cemented vertebral bodies.

PMID- 21191608
TI  - The effect of prepregnancy body mass index on singleton cesarean delivery among
      term nulliparous women in Japanese population.
AB  - PURPOSE: Overweight or obesity is a known risk factor for cesarean delivery
      although there is minimal data among Japanese women. The aim of the study was to
      examine the effect of prepregnancy body mass index (BMI) on singleton cesarean
      delivery among term nulliparous women using a national sample from the Human Milk
      Survey. METHODS: Data from the Human Milk Survey between 1998 and 2008 were used
      for the secondary analysis. Women were categorized as underweight (BMI < 18.5
      kg/m(2)), normal weight (18.5 <= BMI < 25.0), or overweight (BMI >= 25.0) based
      on their prepregnancy BMI. The association between maternal prepregnancy BMI and
      cesarean delivery was assessed using logistic regression models. RESULTS: A total
      of 915 women were included in the analysis. The proportion of cesarean section
      was 10.1%. Overall, 17.1% of the women were underweight while 6.0% were
      overweight. After adjusting for maternal age, smoking status, pregnancy
      complications, and infant birthweight, overweight women were 2.7 times more
      likely to have a cesarean delivery compared to normal weight women (adjusted odds
      ratio [adjusted OR] = 2.7, 95% confidence interval [CI] = 1.4-5.4), and
      underweight women were half as likely to have a cesarean delivery compared to
      normal weight women (adjusted OR = 0.5, 95% CI = 0.2-1.1). CONCLUSIONS: Being
      overweight before pregnancy more than doubled the risk of cesarean delivery
      independent of age, smoking, pregnancy complications, and infant birthweight
      among term nulliparous women. Overweight Japanese women should be advised to
      achieve normal prepregnancy BMI in their preconception period to prevent cesarean
      delivery.

PMID- 21191609
TI  - Benign paroxysmal positional vertigo nurse-led follow-up clinic.
AB  - Patients with benign paroxysmal positional vertigo (BPPV) often require multiple
      appointments for treatment with Epley manoeuvres. Waiting times for medical
      follow up can be very long. To reduce waiting times and increase availability of
      ENT outpatients' appointments, a nurse-led dizziness clinic (NLDC) to follow up
      BPPV patients was established. Prospective audit of 99 consecutive patients
      attending the NLDC, at which patients are assessed and treated, was conducted.
      Non-responders are redirected for further medical review. 99 patients were seen
      in 200 appointments in the NLDC from July 2007 to May 2009. The mean time to NLDC
      was 16 days. 67 patients were discharged from the NLDC free of symptoms. Cost
      analysis revealed savings of L3,800. A survey of NLDC attendees revealed that the
      care they received was rated as excellent, very good or good by 92% of patients.
      In conclusion, the NLDC is an innovation which increases availability of ENT
      outpatient appointments. This is acceptable to patients and is a natural
      extension of the roles of ENT nurse practitioners which could be implemented in
      other ENT departments.

PMID- 21191610
TI  - Optimized voxel brain morphometry: association between brain volumes and the
      response to atypical antipsychotics.
AB  - To date, few studies have addressed the relationship between brain structure
      alterations and responses to atypical antipsychotics in schizophrenia. To this
      end, in this study, magnetic resonance imaging (MRI) and voxel-based morphometry
      (VBM) were used to assess the relationship between the brain volumes of gray (GM)
      and white (WM) matters and the clinical response to risperidone or olanzapine in
      30 schizophrenia patients. In comparison with healthy controls, the patients in
      this study showed a bilateral decrease in the anteromedial cerebellar
      hemispheres, the rectal gyrus and the insula, together with bilateral increases
      in GM in the basal ganglia. Both patient groups had a significantly smaller
      volume of WM in a region encompassing the internal and external capsules as
      compared to the controls. We found an inverse association between striatal size
      and the degree of clinical improvement, and a direct association between the
      degree of insular volume deficit and its improvement. The non-responder patient
      group showed a significant decrease in their left rectal gyrus as compared with
      the responder group. This study reveals a pattern of structural alterations in
      schizophrenia associated with the response to risperidone or olanzapine.

PMID- 21191611
TI  - Bio-medicolegal scientific research in Europe: a comprehensive bibliometric
      overview.
AB  - In times of globalisation, the future of bio-medicolegal sciences in Europe
      depends on the scientific community's ability to develop new strategies for
      research, to introduce new and generally accepted standards, to develop new
      analytical methods, all in order to draw up inter-site, multidisciplinary and
      interdisciplinary long-term research projects, eligible for European Union (EU)
      funding. To analyse the scientific output and to identify the topics of greatest
      interest and appeal in these sciences, an innovative method has been developed to
      select and analyse publications. This method has been applied to analyse a total
      of 21,176 records from PubMed out of which 5,826 papers were suitable for further
      analysis because they were published in national and international journals in
      the time between January 1, 2005 and June 1, 2010 by European authors in the
      field of interest. In 69% of all manuscripts, authors presented results of
      systematic research (original articles); 84% of the papers were written in
      English language. The cumulative impact factor increased from 1,670 points in
      2005 to 1,878 in 2009, and extrapolated 2,812 points in 2010. The most frequent
      topics were the description of new analytical methods in forensic toxicology
      (5.7% of all papers), the analysis of short tandem repeat systems (STR, 5.6%) as
      well as the analysis of injury mechanisms in forensic pathology and clinical
      forensic medicine (4.9%). If the impact factor related potential of different
      topics is calculated (ratio of frequency of papers and frequency of impact points
      achieved), SIDS research reaches 1.64 points, followed by studies on mtDNA (1.59)
      and the development of new analytical methods in forensic toxicology (1.49). The
      findings made in the present bibliometric analysis reveal a clear and interesting
      overall picture of the European scientific production and productivity and could
      be used to identify the most innovative research lines.

PMID- 21191612
TI  - The impact of axial length on retinal tamponade for gas, silicone oil, and heavy
      silicone oil, using an in vitro model.
AB  - BACKGROUND: To investigate whether ocular axial length influences the tamponade
      efficacy of three commonly used agents: gas, silicone oil, and heavy silicone
      oil. METHODS: A series of filling experiments was conducted using 19-mm and 25-mm
      surface-modified spherical model eye chambers to mimic the vitreous cavity. For
      each agent, tamponade efficacy was assessed across a range of percentage fills,
      and comparison was made between the two model eye chambers. The behavior of each
      tamponade agent was quantified by measuring (1) the maximum height of the
      tamponade bubble, and calculating (2) the arc of retinal contact subtended by the
      tamponade bubble. RESULTS: Polynomial regression analysis found no statistically
      significant difference between the regression models for the different-sized
      model eye chambers for bubble height or arc of retinal contact subtended. This
      applied to all of the tamponade agents under investigation. CONCLUSIONS: Across
      the range of cavity sizes under investigation, no significant difference in
      tamponade efficacy (as reflected by the measured dimensions of the tamponade
      bubble) was identified.

PMID- 21191613
TI  - An unusual and potentially misleading phenotypic change in a primary
      gastrointestinal stromal tumour (GIST) under imatinib mesylate therapy.
AB  - We present a unique case of a 62-year-old female who was diagnosed with a huge
      gastric gastrointestinal stromal tumour (GIST). Core needle biopsy revealed a
      cellular spindle cell GIST with diffuse expression of CD117 and CD34. Four
      mitotic figures were counted in ten available HPFs, indicating a high-risk
      tumour. Computed tomography scan, performed after 8 months of neoadjuvant
      imatinib mesylate treatment (Glivec, 400 mg/day), revealed a partial response
      with reduction of tumour size from 20 * 15 * 15 cm to 13.3 * 8 * 7.6 cm. The
      patient underwent complete tumour resection. The tumour revealed extensive cystic
      changes and hyalinisation in 90% of the tumour mass. Multiple viable tumour
      clones, measuring up to 1 cm, showed highly anaplastic, large epithelioid cells
      with vesicular nuclei and prominent, centrally located nucleoli, strikingly
      mimicking the appearance of proximal-type epithelioid sarcoma, anaplastic
      carcinoma, melanoma or epithelioid angiosarcoma. These anaplastic tumour cells
      expressed pankeratin (KL-1) and vimentin, but they were completely negative for
      CD117, DOG-1, CD34, S100, desmin, alpha-smooth muscle actin, HMB45, CD30, CD45,
      CK7, CK20 and 34betaE-12. Sufficient tissue for molecular analysis was available
      from the resected tumour. No mutations were detected in KIT exons 9, 11, 13, 17,
      PDGFRA exons 12, 14, 18, KRAS and BRAF. The patient was alive with no evidence of
      recurrence 28 months later. To our knowledge, this represents the first report on
      this unusual type of trans-differentiation in GIST under imatinib therapy.
      Awareness of this phenomenon would help to avoid diagnostic confusion when
      evaluating post-treatment resections from GISTs.

PMID- 21191614
TI  - Attention-deficit hyperactivity disorder in children chronically exposed to high
      level of vehicular pollution.
AB  - The purpose of this study is to explore whether sustained exposure to vehicular
      air pollution affects the behavior and activities of children. The prevalence of
      attention-deficit hyperactivity disorder (ADHD) was assessed in two childhood
      populations. In a cross-sectional study 969 school-going children (9-17 years)
      and 850 age- and sex-matched children from rural areas were assessed, following
      the criteria of Diagnostic and Statistical Manual of conduct disorders (DSM-IV)
      of American Pediatric Association. Data of ambient particulate matter with a
      diameter of less than 10 MUm (PM10) were obtained from Central Pollution Control
      Board and aerosol monitor. ADHD was found in 11.0% of urban children in contrast
      to 2.7% of the control group (p < 0.001). Major risk factors were male gender,
      lower socioeconomic status, 12-14 year age group, and PM10 level in breathing
      air. ADHD was more prevalent among boys both in urban and rural areas. It was
      prevalent among 18.0% of the boys enrolled in Delhi against 4.0% of the girls,
      giving a male/female ratio of 4.5:1. Inattentive type of ADHD was predominant
      followed by hyperactive-impulsive type and combined type of ADHD. Controlling
      potential confounder, ambient PM10 level was positively correlated with ADHD (OR
      = 2.07; 95% CI, 1.08-3.99). CONCLUSION: The results of this study point to a
      possible association between air pollution and behavioral problems in children.
      Though gender, socioeconomic status, and age play a very important factor in ADHD
      prevalence, the association is highest and strongest between particulate
      pollution and prevalence of ADHD.

PMID- 21191615
TI  - Differential expression of the bone and the liver tissue non-specific alkaline
      phosphatase isoforms in brain tissues.
AB  - The enzyme tissue non-specific alkaline phosphatase (TNAP) belongs to the
      ectophosphatase family. It is present in large amounts in bone in which it plays
      a role in mineralization but little is known about its function in other tissues.
      Arguments are accumulating for its involvement in the brain, in particular in
      view of the neurological symptoms accompanying human TNAP deficiencies. We have
      previously shown, by histochemistry, alkaline phosphatase (AP) activity in monkey
      brain vessels and parenchyma in which AP exhibits specific patterns. Here, we
      clearly attribute this activity to TNAP expression rather than to other APs in
      primates (human and marmoset) and in rodents (rat and mouse). We have not found
      any brain-specific transcripts but our data demonstrate that neuronal and
      endothelial cells exclusively express the bone TNAP transcript in all species
      tested, except in mouse neurons in which liver TNAP transcripts have also been
      detected. Moreover, we highlight the developmental regulation of TNAP expression;
      this also acts during neuronal differentiation. Our study should help to
      characterize the regulation of the expression of this ectophosphatase in various
      cell types of the central nervous system.

PMID- 21191616
TI  - Formation of ethyl acetate by Kluyveromyces marxianus on whey: studies of the
      ester stripping.
AB  - Kluyveromyces marxianus is capable of converting lactose into ethyl acetate
      offering a chance for an economical reuse of whey. The microbial formation of
      ethyl acetate as a bulk product calls for an aerobic process and, thus, the
      highly volatile ethyl acetate is discharged from the aerated bioreactor. This
      stripping process was modeled and investigated experimentally. The stripping rate
      was proportional to the gas flow and nearly independent of the stirring rate
      since the stripping was governed by the absorption capacity of the exhaust gas
      rather than the phase transfer. Cooling the exhaust gas did not noticeably
      influence the stripping. One batch experiment is presented in detail to
      demonstrate the formation of ethyl acetate by K. maxianus DSM 5422 on whey.
      Further batch experiments showed that a substantial formation of ethyl acetate
      only occurred when the yeast growth was limited by a lack of trace elements. The
      highest product yield observed was 0.25 g ethyl acetate per g lactose which is
      nearly 50% of the theoretical maximum.

PMID- 21191617
TI  - Erratum to: Solvent-free geranyl oleate production by enzymatic esterification.
AB  - This study reports the maximization of geranyl oleate production by
      esterification of geraniol and oleic acid in a solvent-free system using a
      commercial lipase as catalyst. The operating conditions that maximized geranyl
      oleate production were determined to be 40  degrees C, geraniol to oleic acid
      molar ratio of 5:1, 150 rpm and 10 wt% of enzyme, with a resulting reaction
      conversion of about 93%. After determining the best reaction parameters, a
      kinetic study was performed and the results obtained in this step allow to
      conclude that an excess of alcohol (alcohol to acid molar ratio of 5:1),
      relatively low enzyme concentration (5 wt%) and temperature of 50  degrees C
      afforded nearly complete reaction conversion after 1 h of reaction. New
      experimental data on enzymatic esterification of geraniol and oleic acid for
      geranyl oleate production are reported in this work, showing a promising
      perspective of the technique to overcome the inconvenience of the chemical
      catalyzed route.

PMID- 21191618
TI  - Suggested revision of the National High Blood Pressure Education Program blood
      pressure standardization for use in severely growth retarded children.

PMID- 21191619
TI  - Influence of arbuscular mycorrhiza on organic solutes in maize leaves under salt
      stress.
AB  - A pot experiment was conducted to examine the effect of the arbuscular
      mycorrhizal (AM) fungus, Glomus mosseae, on plant biomass and organic solute
      accumulation in maize leaves. Maize plants were grown in sand and soil mixture
      with three NaCl levels (0, 0.5, and 1.0 g kg(-1) dry substrate) for 55 days,
      after 15 days of establishment under non-saline conditions. At all salinity
      levels, mycorrhizal plants had higher biomass and higher accumulation of organic
      solutes in leaves, which were dominated by soluble sugars, reducing sugars,
      soluble protein, and organic acids in both mycorrhizal and non-mycorrhizal
      plants. The relative abundance of free amino acids and proline in total organic
      solutes was lower in mycorrhizal than in non-mycorrhizal plants, while that of
      reducing sugars was higher. In addition, the AM symbiosis raised the
      concentrations of soluble sugars, reducing sugars, soluble protein, total organic
      acids, oxalic acid, fumaric acid, acetic acid, malic acid, and citric acid and
      decreased the concentrations of total free amino acids, proline, formic acid, and
      succinic acid in maize leaves. In mycorrhizal plants, the dominant organic acid
      was oxalic acid, while in non-mycorrhizal plants, the dominant organic acid was
      succinic acid. All the results presented here indicate that the accumulation of
      organic solutes in leaves is a specific physiological response of maize plants to
      the AM symbiosis, which could mitigate the negative impact of soil salinity on
      plant productivity.

PMID- 21191620
TI  - Molecular characterization of pezizalean ectomycorrhizas associated with pinyon
      pine during drought.
AB  - Recent studies using molecular analysis of ectomycorrhizas have revealed that
      ascomycete fungi, especially members of the order Pezizales, can be important
      members of ectomycorrhizal (EM) fungal communities. However, little is known
      about the ecology and taxonomy of many of these fungi. We used data collected
      during a wet and a dry period to test the hypothesis that pezizalean EM fungi
      associated with pinyon pine (Pinus edulis) responded positively to drought
      stress. We also assessed the phylogenetic relationships among six, unknown
      pezizalean EM fungi, common to our study sites, using rDNA sequences from the
      internal transcribed spacer and large subunit (LSU) regions of the ribosomal DNA.
      Sequences of these fungi were then compared to sequences from known taxa to allow
      finer-scale identification. Three major findings emerged. First, at two sites,
      pezizalean EM were 44-95% more abundant during a dry year than a wetter year,
      supporting the hypothesis that pezizalean EM fungi respond positively to dry
      conditions. Second, four of the six unknown pezizalean EM fungi associated with
      P. edulis separated from one another consistently regardless of site or year of
      collection, suggesting that they represented distinct taxa. Third, comparison
      with LSU sequences of known members of the Pezizales indicated that these four
      taxa grouped within the genus Geopora of the family Pyronemataceae. Our results
      provide further evidence of the importance of pezizalean fungi in the
      ectomycorrhizal symbiosis and demonstrate high local abundance of members of the
      genus Geopora in drought-stressed pinyon-juniper woodlands.

PMID- 21191621
TI  - Recurrent adjacent segment disease and cauda equina syndrome.
AB  - PURPOSE: A case of cauda equina lesion as a result of recurrent adjacent segment
      degeneration (ASD) after multiple lumbar fusions is reported. ASD might be a
      consequence of biomechanical overload or simply a normal degenerative process.
      The reported clinical relevance of ASD is rather low. We describe an unusual case
      of cauda equina compression at L1-L2 in a patient who had undergone L2-L4 fusion
      8 years previously and 2 decompression-fusion surgeries 16 years before.
      MATERIALS AND METHODS: A 72-year-old man, who had two previous lumbar fusion
      decompression procedures, underwent a third lumbar surgery in December 2000 to
      treat symptomatic spinal canal stenosis associated with L3-L4 pseudoarthrosis.
      After a symptom-free period of 8 years, the patient experienced low back pain
      radiating to both legs while standing, associated with saddle sensory
      disturbances and incontinence. Physical examination ruled out significant motor
      deficits. Plain radiographs showed solid fusion from L2 to L4, good spinal
      alignment, and low-grade L1-L2 retrolisthesis. Stainless steel pedicular
      instrumentation distorted magnetic resonance imaging, preventing adequate spinal
      canal evaluation. Electromyography demonstrated signs of cauda equina compression
      (bilateral L3-S2). CT myelography showed a stop at L1-L2, due to a severe spinal
      canal stenosis. L1-L2 decompression and fusion were performed. RESULTS: After an
      uneventful surgery with no complications, the symptoms abated and incontinence
      recovered. CONCLUSIONS: Even if the reported clinical relevance of ASD is very
      low, fused patients with a constitutional narrow spinal canal are at risk of
      developing severe neural compression at the level adjacent to the fusion.

PMID- 21191622
TI  - Type 2 diabetes quality of life patients treated with insulin and oral
      hypoglycemic medication.
AB  - The aim of the study is to assess QoL depending on the choice of therapeutic
      regimen. From a total of 200 patients, half (n = 100) were treated with insulin
      (66% were females, age 52.1 +/- 7.4-group A), the remaining 100 received oral
      treatment (74% females, age 63.3 +/- 8.3-group B). For self-assessment of QoL,
      the WHOQOL-BREF questionnaire was used. In group A, we found a negative influence
      of increased level of glycemia and occurrence of coexisting diseases in the
      somatic domain . In the psychological domain, frequent checkups showed a positive
      influence while circulatory failure produced negative results. For social domain,
      disobeying of recommended diet was strongly negative as well as increased levels
      of glycemia and coexisting disease for environmental domain. In group B, for
      somatic domain, correct values of glycemia and place of residence had positive
      influence. Incorrect values of BMI, WHR, and co-existing disease influenced the
      same domain negatively. In the psychological domain, a positive influence had
      place of residence but a negative BMI, ischemic heart disease, clinical
      complications. For environmental domain, a positive influence had correct values
      of glycemia but a negative BMI, ischemic heart disease and clinical
      complications. Finally, the social domain for group B was negatively influenced
      by BMI, ischemic heart disease, clinical complications, and lack of regular
      supervisions of glycemia level. A higher assessment of quality of life was found
      in the group of patients treated with oral hypoglycemic medicines in somatic and
      environmental domains, and in the group of patients treated with insulin in
      psychological domain.

PMID- 21191623
TI  - Involvement of the subthalamic nucleus and globus pallidus internus in attention.
AB  - We studied the appearance of cognitive event-related potentials (ERPs) and event
      related de/synchronizations (ERD/S) in the subthalamic nucleus (STN) and globus
      pallidus internus (GPi). We particularly focused on the rare non-target
      (distractor) stimuli processing. ERPs and ERD/S in the alpha and beta frequency
      range were analyzed in seven Parkinson's disease patients and one primary
      dystonia patient with implanted deep brain stimulation (DBS) electrodes. A visual
      three-stimulus protocol was used (frequent stimulus, target stimulus, and
      distractor). The non-target and distractor-related waveforms manifested similar
      shapes. A specific positive ERP peak around 200 ms and a low alpha frequency ERS
      were detected from the STN as a response to the distractor stimuli in six of the
      patients with Parkinson's disease and also in the primary dystonia patient's GPi.
      This positivity probably reflects an attentional orienting response to the
      distractor stimuli. The STN and GPi are probably involved in attentional cerebral
      networks.

PMID- 21191624
TI  - The effects of pargyline and 2-phenylethylamine on D1-like dopamine receptor
      binding.
AB  - 2-Phenylethylamine (PE) potentiates neuronal responses to dopamine by an unknown
      post-synaptic mechanism. Here, whether PE modifies D1-like receptor binding was
      examined. An unexpected effect of the monoamine oxidase inhibitor pargyline was
      observed, which did not involve competition for ligand binding. PE did not affect
      ligand binding in the presence or absence of pargyline. It is concluded that the
      effect of pargyline does not involve elevation of endogenous PE, and PE effects
      on dopaminergic neurotransmission are not due to altered D1-like receptor
      binding.

PMID- 21191625
TI  - Prevalence of hepatitis E virus among swine and humans in two different ethnic
      communities in Indonesia.
AB  - The purpose of this study was to investigate the prevalence of hepatitis E virus
      (HEV) infection in swine and humans in different environments in Java and Bali,
      Indonesia. The prevalence of anti-HEV antibodies in people over 20 years old
      living in communities in Bali was significantly higher than that in Java. While
      68.8% and 90.0% of swine in Bali were anti-HEV positive at 1 and 2 months of age,
      respectively, swine in Java were at significantly lower risk of HEV infection by
      the age of 2 months. Our present data suggest that substantial differences in
      swine-breeding conditions and human living environments affect the rate of HEV
      infection in humans and swine.

PMID- 21191626
TI  - Salvage of an infected titanium mesh in a large incisional ventral hernia using
      medicinal honey and vacuum-assisted closure: a case report and literature review.
AB  - The overall reported percentage of mesh infections is 1.3%. Infections after
      incisional ventral hernia repair depend on many factors. Salvaging an infected
      mesh should be the priority, because serious complications are reported following
      mesh removal. In this case report, a methicillin-resistant Staphylococcus aureus
      (MRSA)-infected titanium mesh was salvaged by a novel technique, not requiring
      removal. The combination of vacuum-assisted closure (VACTM therapy) of the wound
      and medical honey (L-MesitranTM) proved to be successful in leaving the mesh in
      situ. We report the successful management of this infected titanium mesh and
      review the literature regarding the possible pathogenetic mechanisms and
      treatment options.

PMID- 21191627
TI  - Emergence of daptomycin resistance following vancomycin-unresponsive
      Staphylococcus aureus bacteraemia in a daptomycin-naive patient--a review of the
      literature.
AB  - A patient developed a daptomycin-resistant methicillin-resistant Staphylococcus
      aureus (MRSA) infection, despite being daptomycin-naive, in the setting of
      persistent bacteraemia secondary to vertebral osteomyelitis. Modified population
      analysis profiling of sequential MRSA blood culture isolates revealed transition
      from a vancomycin-susceptible phenotype to a vancomycin-intermediate S. aureus
      (VISA) phenotype through a vancomycin-heteroresistant S. aureus (hVISA)
      intermediary. Increased cell wall thickening, determined by transmission electron
      microscopy, correlated with the emergence of daptomycin resistance. This case
      supports the current hypothesis that MRSA with reduced glycopeptide
      susceptibility are less susceptible to daptomycin because of a thickened cell
      wall. This may have significance for the use of daptomycin in salvage therapy.
      Other predictors of daptomycin resistance include bacteraemic persistence and the
      presence of high inoculum infections. As resistance may appear de novo and be
      unstable in vivo, all isolates should have daptomycin susceptibility testing
      performed. The optimal antibiotic option for salvage therapy of these daptomycin
      resistant infections is unknown. However, these findings emphasise the importance
      of optimising management, including the consideration of early surgical
      intervention to avoid the emergence of daptomycin resistance, especially in high
      inoculum infections.

PMID- 21191628
TI  - Growth-induced buckling of an epithelial layer.
AB  - We use a proof-of-concept experiment and two mathematical models to explore
      growth-induced tissue buckling, as may occur in colorectal crypt formation. Our
      experiment reveals how growth of a cultured epithelial monolayer on a thin
      flexible substrate can cause out-of-plane substrate deflections. We describe this
      system theoretically using a 'bilayer' model in which a growing cell layer
      adheres to a thin compressible elastic beam. We compare this with the 'supported
      monolayer' model due to Edwards and Chapman (Bull Math Biol 69:1927-1942, 2007)
      for an incompressible expanding beam (representing crypt epithelium), which
      incorporates viscoelastic tethering to underlying stroma. We show that the
      bilayer model can exhibit buckling via parametric growth (in which the system
      passes through a sequence of equilibrium states, parameterised by the total beam
      length); in this case, non-uniformities in cell growth and variations in cell
      substrate adhesion are predicted to have minimal effect on the shape of resulting
      buckled states. The supported-monolayer model reveals how competition between
      lateral supports and stromal adhesion influences the wavelength of buckled states
      (in parametric growth), and how non-equilibrium relaxation of tethering forces
      influences post-buckled shapes. This model also predicts that non-uniformities in
      growth patterns have a much weaker influence on buckled shapes than non
      uniformities in material properties. Together, the experiment and models support
      the concept of patterning by growth-induced buckling and suggest that targeted
      softening of a growing cell layer provides greater control in shaping tissues
      than non-uniform growth.

PMID- 21191629
TI  - Tumor necrosis factor-alpha induces expression and release of interleukin-6 by
      human urothelial cells.
AB  - OBJECTIVE: We examined the effects of tumor necrosis factor-alpha (TNF-alpha) on
      expression and release of interleukin-6 (IL-6) by human urothelial cells (HUCs)
      and investigated whether the effects of TNF-alpha are mediated by mitogen
      activated protein kinase (MAPK) pathways. MATERIALS AND METHODS: HUCs were
      treated with TNF-alpha at 1-10 ng/ml for 2-24 h. Expression of IL-6 and TNF-alpha
      receptor 1 (TNFR1) mRNAs were examined by real-time PCR. The release of IL-6 into
      culture medium was determined by ELISA. The presence of TNFR1 protein and TNF
      alpha-induced activation of MAPK pathways was examined by immunoblotting
      analysis. The effects of selective blockers of MAPK pathways on TNF-alpha-induced
      IL-6 expression and release were determined. RESULTS: TNF-alpha increased IL-6
      mRNA expression and stimulated release of IL-6 in a concentration- and time
      dependent manner. The effects of TNF-alpha were mediated by TNFR1. TNF-alpha
      induced phosphorylation of ERK1/2 and JNK, and TNF-alpha-induced IL-6 expression
      and release were inhibited by selective ERK1/2 and JNK blockers. CONCLUSIONS:
      These results demonstrate that TNF-alpha increases expression and release of IL-6
      by HUCs and that the effects of TNF-alpha are mediated by TNFR1. Also, the ERK1/2
      and JNK pathways are involved in TNF-alpha-induced expression and release of IL-6
      in HUCs and may represent therapeutic targets in inflammatory urinary tract
      diseases.

PMID- 21191630
TI  - Genetic variations in VEGF and VEGFR2 and glioblastoma outcome.
AB  - Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) are central
      components in the development and progression of glioblastoma. To investigate if
      genetic variation in VEGF and VEGFR2 is associated with glioblastoma prognosis,
      we examined blood samples from 154 glioblastoma cases collected in Sweden and
      Denmark between 2000 and 2004. Seventeen tagging single nucleotide polymorphisms
      (SNPs) in VEGF and 27 in VEGFR2 were genotyped and analysed, covering 90% of the
      genetic variability within the genes. In VEGF, we found no SNPs associated with
      survival. In VEGFR2, we found two SNPs significantly associated to survival,
      namely rs2071559 and rs12502008. However, these results are likely to be false
      positives due to multiple testing and could not be confirmed in a separate
      dataset. Overall, this study provides little evidence that VEGF and VEGFR2
      polymorphisms are important for glioblastoma survival.

PMID- 21191631
TI  - A geographical genetics framework for inferring homing reproductive behavior in
      fishes.
AB  - One of the most intriguing patterns of migration and gene flow that affects
      genetic structure is the reproductive homing behavior of fishes, wherein the
      adults return to the areas in which they were spawned. Here we reviewed the
      literature on homing behavior in fish and propose an analytical framework for
      testing hypotheses regarding this behavior and its effects on the genetic
      structure of fish in an explicit geographical context, using a geographical
      genetics toolbox. Although disentangling the many potential causes underlying
      genetic population structure and unambiguously demonstrating that the homing
      behavior causes these genetic patterns is difficult, our framework allows the
      successive testing of homing behavior with increasing levels of complexity based
      on the following: (1) establishment of population structures among waterheads;
      (2) patterns of genetic variability throughout the adult migratory pool; (3)
      analyses of the non-migratory adult pool; and (4) comparisons among successive
      generations. We expect that the framework presented here will help delineating
      the appropriate uses of different sampling designs to make inferences regarding
      homing behavior and illustrate the limits imposed by the interpretation of
      different types of genetic data. More importantly, we hope this framework enables
      researchers to understand how a particular dataset can be utilized in a broader
      context as an ongoing part of a larger research program and thus guide future
      research by developing better and more integrated sampling designs.

PMID- 21191632
TI  - Physical activity during pregnancy in a prospective cohort of British women:
      results from the Avon longitudinal study of parents and children.
AB  - We sought to examine the levels, types, and changes of physical activity and
      their correlates among pregnant women. Data came from 9,889 pregnant women with
      due dates between April 1, 1991 and December 31, 1992 who were participants of
      the Avon Longitudinal Study of Parents and Children (ALSPAC) in Bristol, Avon,
      Southwest England. Self-reported physical activity during pregnancy was collected
      via questionnaires administered at 18 and 32 weeks of gestation. We found, at 18
      weeks of gestation, the prevalence of engaging in physical activity that was
      sufficient to cause sweating for >= 3 h/week (referred to as strenuous physical
      activity) was 48.8%. This percentage was similar at 32 weeks of gestation. The
      most common physical activity during pregnancy reported by these women was brisk
      walking, followed by swimming and ante-natal exercise. In models that mutually
      adjusted for all characteristics examined, younger women, women in lower social
      classes, those not employed during pregnancy, married and parous women (compared
      to those not in each of these groups) were more likely to report engaging in
      strenuous physical activity. After becoming pregnant, about two out of three of
      these women reported reducing physical activity levels at 18 weeks of gestation.
      In mutually adjusted models, women who were younger, fit and well, parous, and
      women from lower social classes (compared to those not in each of these groups)
      were less likely to report reducing their physical activity. Our findings provide
      insights that are relevant to the design of future observational and intervention
      studies concerned with the effects of physical activity during pregnancy on
      health outcomes for mothers and offspring.

PMID- 21191633
TI  - Blocking IKKalpha expression inhibits prostate cancer invasiveness.
AB  - PURPOSE: IKKalpha has been recently identified as a key mediator of the
      inflammation and metastasis in prostate cancer. In the present study, we intend
      to silence the IKKalpha expression in prostate cancer cells using synthetic
      siRNAs and examine their biological effects on tumor cell invasiveness and
      growth. METHODS: Three synthetic siRNAs targeting different regions of the
      IKKalpha mRNA were designed, and the silencing effect was determined in PC-3 and
      DU145 cells. Numerous studies, including wound-healing assay, migration assay,
      invasion assay, cell attachment assay, cell proliferation, and cell cycle
      analysis, were conducted to investigate the biological effects of the IKKalpha
      siRNAs on prostate cancer cells. RESULTS: We have identified potent siRNAs that
      can silence the IKKalpha up to 74%. Inhibition of IKKalpha reduced the wound
      healing, migration, invasion and cell attachment capabilities of prostate cancer
      cells. Similar anti-invasive effects were also observed in the presence of RANKL.
      However, silencing of IKKalpha only showed a negligible effect on cell
      proliferation and cell cycle distribution. CONCLUSION: This study presents
      compelling evidence that IKKalpha plays a major role in prostate cancer invasion
      and metastasis, but not in cell proliferation. Silencing of IKKalpha with siRNA
      may therefore provide a promising therapeutic strategy for prostate cancer
      patients.

PMID- 21191635
TI  - Validation of the Chinese version of the gambling motivation scale (C-GMS).
AB  - The French items of the Gambling Motivation Scale (GMS) were first developed and
      validated by Chantal and colleagues in 1994. The scale then became one of the
      most widely used motivational scales in the gambling literature of the West. The
      present study recruited 932 Chinese university students in order to validate the
      Chinese version of the Gambling Motivation Scale (C-GMS). The results of a
      confirmatory factor analysis of the Chinese data supported the 7-factor model as
      proposed by Chantal et al. (Soc Leis 17:189-212, 1994). This study also found a
      second-order model with three major factors, which corresponded to three types of
      gambling motivation including self-determined motivation (for knowledge, for
      accomplishment, for stimulation, and due to identified regulation), non self
      determined motivation (due to introjected regulation and external regulation),
      and amotivation. All subscales demonstrated satisfactory internal consistency,
      and showed significant correlations with gambling correlates such as problem
      gambling symptoms and gambling intention. In sum, the C-GMS showed adequate
      psychometric properties and can be extended for use with Chinese populations.

PMID- 21191634
TI  - Hydrodynamic gene delivery and its applications in pharmaceutical research.
AB  - Hydrodynamic delivery has emerged as the simplest and most effective method for
      intracellular delivery of membrane-impermeable substances in rodents. The system
      employs a physical force generated by a rapid injection of large volume of
      solution into a blood vessel to enhance the permeability of endothelium and the
      plasma membrane of the parenchyma cells to allow delivery of substance into
      cells. The procedure was initially established for gene delivery in mice, and its
      applications have been extended to the delivery of proteins, oligo nucleotides,
      genomic DNA and RNA sequences, and small molecules. The focus of this review is
      on applications of hydrodynamic delivery in pharmaceutical research. Examples are
      provided to highlight the use of hydrodynamic delivery for study of
      transcriptional regulation of CYP enzymes, for establishment of animal model for
      viral infections, and for gene drug discovery and gene function analysis.

PMID- 21191636
TI  - Pathological gambling and posttraumatic stress disorder: a study of the co
      morbidity versus each alone.
AB  - This report is the first empirical study to compare pathological gambling (PG),
      posttraumatic stress disorder (PTSD), and their co-occurrence. The sample was 106
      adults recruited from the community (35 with current PG; 36 with current PTSD,
      and 35 with BOTH). Using a cross-sectional design, the three groups were
      rigorously diagnosed and compared on various measures including
      sociodemographics, psychopathology (e.g., dissociation, suicidality, comorbid
      Axis I and II disorders), functioning, cognition, life history, and severity of
      gambling and PTSD. Overall, the PG group reported better psychological health and
      higher functioning than PTSD or BOTH; and there were virtually no differences
      between PTSD and BOTH. This suggests that it is the impact of PTSD, rather than
      comorbidity per se, that appears to drive a substantial increase in symptoms. We
      also found high rates of additional co-occurring disorders and suicidality in
      PTSD and BOTH, which warrants further clinical attention. Across the total
      sample, many reported a family history of substance use disorder (59%) and
      gambling problems (34%), highlighting the intergenerational impact of these. We
      also found notable subthreshold PTSD and gambling symptoms even among those not
      diagnosed with the disorders, suggesting a need for preventive care. Dissociation
      measures had mixed results. Discussion includes methodology considerations and
      future research areas.

PMID- 21191638
TI  - The limitations of nonlinear fluorescence effect in super resolution saturated
      structured illumination microscopy system.
AB  - Classically, optical systems are considered to have a fundamental resolution
      limit due to diffraction. Many strategies for improving both axial and lateral
      resolutions are based on a priori information about the input signal. These
      strategies lead to a numerical aperture improvement. However these are still
      limited by the wave nature of light. By using fluorescence technique one
      theoretically can reach unlimited resolution. The key point is to use the
      nonlinear dependence of the fluorescence emission rate on the intensity of the
      applied illumination. In this paper we present simulation as well as experimental
      results which show the advantage and the problems of using the nonlinear
      fluorescence effect in super resolution systems as well as discussing the
      nonlinear phenomena concerning the fluorescence process. The results show that
      the nonlinear fluorescence effect is accompanied by severe quenching, bleaching
      and saturation phenomena. As consequence, super resolution using saturated
      structured illumination method in living biological samples becomes severely
      restricted.

PMID- 21191637
TI  - An eight component decision-making model for problem gambling: a systems approach
      to stimulate integrative research.
AB  - Problem Gambling (PG) represents a serious problem for affected individuals,
      their families and society in general. Previous approaches to understanding PG
      have been confined to only a subset of the psychobiological factors influencing
      PG. We present a model that attempts to integrate potential causal factors across
      levels of organization, providing empirical evidence from the vast literature on
      PG and complimentary literatures in decision-making and addiction. The model
      posits that components are arranged systematically to bias decisions in favor of
      either immediately approaching or avoiding targets affording the opportunity for
      immediate reward. Dopamine, Testosterone and Endogenous Opioids favor immediate
      approach, while Serotonin and Cortisol favor inhibition. Glutamate is involved in
      associative learning between stimuli and promotes the approach response through
      its link to the DA reward system. GABA functions to monitor performance and curb
      impulsive decision-making. Finally, while very high levels of Norepinephrine can
      induce arousal to an extent that is detrimental to sound decision-making, the
      reactivity of the Norepinephrine system and its effects of Cortisol levels can
      shift the focus towards long-term consequences, thereby inhibiting impulsive
      decisions. Empirical evidence is provided showing the effects of each component
      on PG and decision-making across behavioural, neuropsychological, functional
      neuroimaging and genetic levels. Last, an effect size analysis of the growing
      pharmacotherapy literature is presented. It is hoped that this model will
      stimulate multi-level research to solidify our comprehension of biased decision
      making in PG and suggest pharmacological and psychological approaches to
      treatment.

PMID- 21191639
TI  - CXCL10 and CXCL13 Expression were highly up-regulated in peripheral blood
      mononuclear cells in acute rejection and poor response to anti-rejection therapy.
AB  - BACKGROUND: Acute rejection is still one of the main complications which enhances
      the cost and the risk to renal graft failure. Chemokines, interacting with
      respective receptors, can recruit leukocytes into grafts and mediate allograft
      rejection. In this study, we aimed to analyze gene expression of chemokines
      including CCL5/RANTES, CXCL10/IP-10, CXCL13/BCA-1, and receptors of CCR5, CXCR3,
      CXCR5 in peripheral blood mononuclear cells (PBMCs) during acute renal allograft
      rejection METHODS: Gene expression of all these chemokines and receptors in PBMCs
      were analyzed by real-time PCR from 14 stable recipients, 32 biopsy-proven acute
      rejection (AR), and 5 acute tubular necrosis (ATN). RESULTS: Gene expression of
      CCL5, CXCL10, CXCL13, and CCR5 were up-regulated both in AR and ATN group
      compared to stable recipients (fold change>2, P<0.05). Serum creatinine recovered
      to baseline level after anti-rejection therapy was defined as AR-sensitive and
      creatinine maintained above 200 MUmol/L as AR-resistant. Expression of CXCL10 and
      CXCL13 were 5.98-, 2.94-, and 20.5, 10.8-fold change in AR-resistant and AR
      sensitive compared to stable recipients, respectively. The expression of CXCL10
      and CXCL13 was a twofold change in AR-resistant compared to AR-sensitive
      recipients (P<0.05). Five out of ten AR-resistant recipients lost graft function
      in the follow-up. CONCLUSION: CXCL10 and CXCL13 expression were highly up
      regulated in PBMCs in acute renal allograft rejection, especially in poor
      response to anti-rejection therapy and detrimental prognosis.

PMID- 21191640
TI  - The developmental pathway from pubertal timing to delinquency and sexual activity
      from early to late adolescence.
AB  - There is strong evidence that early pubertal timing is associated with adolescent
      problem behaviors. However, there has been limited investigation of the
      mechanisms or developmental relationships. The present study examined
      longitudinal models incorporating pubertal timing, delinquency, and sexual
      activity in a sample of 454 adolescents (9-13 years old at enrollment; 47%
      females). Participants were seen for three assessments approximately 1 year
      apart. Characteristics of friendship networks (older friends, male friends, older
      male friends) were examined as mediators. Structural equation modeling was used
      to test these associations as well as temporal relationships between sexual
      activity and delinquency. Results showed that early pubertal timing at Time 1 was
      related to more sexual activity at Time 2, which was related to higher
      delinquency at Time 3, a trend mediation effect. None of the friendship variables
      mediated these associations. Gender or maltreatment status did not moderate the
      meditational pathways. The results also supported the temporal sequence of sexual
      activity preceding increases in delinquency. These findings reveal that early
      maturing adolescents may actively seek out opportunities to engage in sexual
      activity which appears to be risk for subsequent delinquency.

PMID- 21191642
TI  - Neuropsychological attention skills and related behaviours in adults with
      tuberous sclerosis complex.
AB  - Tuberous sclerosis complex (TSC) is a genetic disorder associated with mTOR over
      activation and disruption of MAPK, PI3K and AMPK signalling. Children with TSC
      have significant deficits on neuropsychological attention tasks, particularly
      dual tasking. Here we investigated attentional skills and related behaviours in
      daily life in normally intelligent adults with TSC and matched controls using the
      Test of Everyday Attention for Children (TEA-Ch) and the Attention-Deficit Scales
      for Adults (ADSA). No group differences were demonstrated on selective or
      sustained attention tasks carried out alone. However, adults with TSC performed
      significantly worse when these tasks were combined in a cross-modal dual task
      condition. On the ADSA the TSC group had significantly worse scores on several
      subscales (attention/concentration, behaviour/disorganization, academic and
      emotional behaviours) compared to controls and these correlated with dual task
      performance, indicating a clear impact of dual task deficits on attention-related
      behaviours in daily life. The presence or absence of epilepsy did not influence
      dual task performance or attention-deficits in daily life. Taken together with
      similar findings in children, results suggest that dual task difficulties are a
      core feature of the neuropsychological phenotype of TSC.

PMID- 21191641
TI  - A computer model of unitary responses from associational/commissural and
      perforant path synapses in hippocampal CA3 pyramidal cells.
AB  - Despite the central position of CA3 pyramidal cells in the hippocampal circuit,
      the experimental investigation of their synaptic properties has been limited.
      Recent slice experiments from adult rats characterized AMPA and NMDA receptor
      unitary synaptic responses in CA3b pyramidal cells. Here, excitatory synaptic
      activation is modeled to infer biophysical parameters, aid analysis
      interpretation, explore mechanisms, and formulate predictions by contrasting
      simulated somatic recordings with experimental data. Reconstructed CA3b pyramidal
      cells from the public repository NeuroMorpho.Org were used to allow for cell
      specific morphological variation. For each cell, synaptic responses were
      simulated for perforant pathway and associational/commissural synapses. Means and
      variability for peak amplitude, time-to-peak, and half-height width in these
      responses were compared with equivalent statistics from experimental recordings.
      Synaptic responses mediated by AMPA receptors are best fit with properties
      typical of previously characterized glutamatergic receptors where perforant path
      synapses have conductances twice that of associational/commissural synapses (0.9
      vs. 0.5 nS) and more rapid peak times (1.0 vs. 3.3 ms). Reanalysis of passive
      cell experimental traces using the model shows no evidence of a CA1-like increase
      of associational/commissural AMPA receptor conductance with increasing distance
      from the soma. Synaptic responses mediated by NMDA receptors are best fit with
      rapid kinetics, suggestive of NR2A subunits as expected in mature animals.
      Predictions were made for passive-cell current clamp recordings, combined AMPA
      and NMDA receptor responses, and local dendritic depolarization in response to
      unitary stimulations. Models of synaptic responses in active cells suggest
      altered axial resistivity and the presence of synaptically activated potassium
      channels in spines.

PMID- 21191643
TI  - An interrupted time series evaluation of a hepatitis C intervention for persons
      with HIV.
AB  - Accurate HCV knowledge is lacking among high-risk groups, including people with
      HIV/AIDS (PLWHA). Liver disease primarily due to HCV has emerged as a serious
      cause of mortality among PLWHA. We used an Interrupted Time Series design to
      evaluate a social-ecologically based intervention for PLWHA, where an infectious
      disease clinic serving a six-county intervention area was monitored before (7
      months) and after (17 months) intervention onset. The intervention included
      education of PLWHA and medical providers, HIV/HCV support groups, and adaptation
      of the patient chart top sheet to include HCV test information. Clinic-level
      outcomes were assessed prospectively every other week for 2 years by interviewing
      patients (n = 259) with clinic appointments on assessment days. Abrupt, gradual
      and delayed intervention effects were tested. Weighted regression analyses showed
      higher average HCV knowledge and a higher prevalence of patients reporting HCV
      discussion with their medical providers after intervention onset. A delayed
      effect was found for HCV awareness, and a gradually increasing effect was found
      for knowing one's HCV status. Other communities may consider adopting this
      intervention. Additional HCV interventions for PLWHA with HIV are needed.

PMID- 21191644
TI  - Changes in stimulant drug use over time in the MACS: evidence for resilience
      against stimulant drug use among men who have sex with men.
AB  - Stimulant drug use is associated with numerous health problems among men who have
      sex with men (MSM). This paper describes how stimulant drug use changes over a
      four and one-half year period from 2003 until 2008. Participants were 2,389 men
      (17,222 person-visits) from The Multicenter AIDS Cohort Study (MACS)-an ongoing,
      prospective study of HIV infection among MSM. Group-based trajectory analyses of
      data from these men over the study period yielded a four groups solution:
      consistent users (9.8%), men whose use increased (5.4%), men whose use declined
      (6.9%), and abstinent or rarely-using men (77.9%). There were significant
      differences between groups in terms of demographic, behavioral risk and HIV
      serostatus. Men who increased or decreased stimulant drug use over time reported
      congruent changes in sexual risk taking. The fact that sexual risk levels
      parallel stimulant drug use over time suggests that finding ways to lower rates
      of stimulant drug use among MSM could be a tool in HIV prevention.

PMID- 21191645
TI  - The effects of Tag-1 on the maturation of mouse cerebellar granule neurons.
AB  - The cell adhesion molecule Tag-1 is highly expressed in immature cerebellar
      granule neurons (CGNs) during axonogenesis and is down-regulated prior to onset
      of radial migration. However, its precise role(s) during development of mammalian
      CGNs has been unclear. Here we studied the effects of anti-Tag-1 function
      blocking antibodies on the development of mouse CGNs in primary cell culture and
      in situ. Interfering antibodies inhibited axon formation by mouse CGNs in both
      cell cultures and in cerebellar slices. Effects on axon extension in cell
      cultures were observed under conditions of homotypic cell-cell contact,
      consistent with inhibition of cell adhesion activity. Further, when used as a
      substratum Tag-1 protein strongly stimulated neurite outgrowth by CGNs.
      Antagonism of Tag-1 also enhanced CGN migration in modified Boyden chamber
      assays. Radial migration was inhibited by Tag-1 antibodies in cerebellar slices,
      possibly reflecting a block in early CGN maturation in situ. These findings are
      consistent with a regulatory role for Tag-1 in axon emergence as well as
      migratory behavior by developing mouse CGNs.

PMID- 21191646
TI  - Comparison of phosphorylated extracellular signal-regulated kinase 1/2
      immunoreactivity in the hippocampal Ca1 region induced by transient cerebral
      ischemia between adult and aged gerbils.
AB  - In this study, the authors examined the difference of phosphorylated
      extracellular signal-regulated kinase 1/2 (pERK1/2) in the hippocampal CA1 region
      (CA1) between adult and aged gerbils after 5 min of transient cerebral ischemia.
      Delayed neuronal death in the CA1 of the aged group was much slower than that in
      the adult group after ischemia/reperfusion (I/R). pERK1/2 immunoreaction was
      observed in the CA1 region of the sham-operated adult gerbil. pERK1/2
      immunoreactivity and protein levels in the ischemic CA1 region of the adult group
      were markedly increased 4 days after I/R, and then reduced up to 10 days after
      I/R. In contrast, pERK1/2 immunoreaction was hardly detected in the CA1 region of
      sham-operated aged gerbils, and the immunoreactivity increased from 1 day after
      the ischemic insult, and still observed until 10 days post-ischemia. In addition,
      pERK1/2-immunoreaction was expressed in astrocytes in the ischemic CA1 region:
      The expression in the ischemia-operated aged gerbils was later than that in the
      ischemia-operated adult gerbils. These results indicate that different patterns
      of ERK1/2 immunoreactivity may be associated with different processes of delayed
      neuronal death in adult and aged animals.

PMID- 21191647
TI  - Evidence that L-carnitine and selenium supplementation reduces oxidative stress
      in phenylketonuric patients.
AB  - It is well established that the involvement of reactive species in the
      pathophysiology of several neurological diseases, including phenylketonuria
      (PKU), a metabolic genetic disorder biochemically characterized by elevated
      levels of phenylalanine (Phe). In previous studies, we verified that PKU patients
      (treated with a protein-restricted diet supplemented with a special formula not
      containing L-carnitine and selenium) presented high lipid and protein oxidative
      damage as well as a reduction of antioxidants when compared to the healthy
      individuals. Our goal in the present study was to evaluate the effect of Phe
      restricted diet supplemented with L-carnitine and selenium, two well-known
      antioxidant compounds, on oxidative damage in PKU patients. We investigated
      various oxidative stress parameters in blood of 18 treated PKU patients before
      and after 6 months of supplementation with a special formula containing L
      carnitine and selenium. It was verified that treatment with L-carnitine and
      selenium was capable of reverting the lipid peroxidation, measured by
      thiobarbituric acid-reactive species, and the protein oxidative damage, measured
      by sulfhydryl oxidation, to the levels of controls. Additionally, the reduced
      activity of glutathione peroxidase was normalized by the antioxidant
      supplementation. It was also verified a significant inverse correlation between
      lipid peroxidation and L-carnitine blood levels as well as a significant positive
      correlation between glutathione peroxidase activity and blood selenium
      concentration. In conclusion, our results suggest that supplementation of L
      carnitine and selenium is important for PKU patients since it could help to
      correct the oxidative stress process which possibly contributes, at least in
      part, to the neurological symptoms found in phenylketonuric patients.

PMID- 21191648
TI  - Traditional-Westernizing continuum of change in screening behaviors: comparison
      between Arab women in Israel and the West Bank.
AB  - Health perceptions are changing, but the pace of change varies across societies,
      exercising different effects on women's screening behaviors. Our aim is to assess
      the rate of mammography and clinical breast examination (CBE) attendance in
      younger and older Arab women in Israel and in the West Bank, and the effect of
      health beliefs on the screening behaviors. A random sample of 697 Arab women, 300
      from Israel and 397 from the West Bank, aged 30-65 years, answered questionnaires
      on screening behaviors, the Arab culture-specific barriers, fatalism, worry, and
      health beliefs. The participation rate was 93.5% in Israel and 98.3% in the West
      Bank. Higher fatalistic perceptions, traditional beliefs, barriers to bodily
      exposure, and social, environmental, and personal barriers to screening were
      reported by women from the West Bank compared to Arab women in Israel and by
      older women compared to the younger women. Adjusted lower likelihood of attending
      screening was predicted by group (AOR 3.55, 95% CI 1.25-10.11 for mammography and
      AOR 2.36, 95% CI 1.19-3.65 for CBE), higher fatalism (AOR 0.52, 95% CI 0.30-76
      for mammography and AOR 0.68, 95% CI 0.54-92 for CBE), more traditional beliefs
      (AOR 0.61, 95% CI 0.48-0.80 for mammography and AOR 0.51, 95% CI 0.39-0.68 for
      CBE), and higher barriers to self-exposure (AOR 0.69, 95% CI 0.48-0.83 for
      mammography and AOR 0.76, 95% CI 0.62-0.95 for CBE), higher perceived personal
      barriers (AOR 0.36, 95% CI 0.12-1.08 for mammography and AOR 0.77, 95% CI 0.60
      0.98 for CBE), and lower perceived benefits (AOR 1.98, 95% CI 1.17-3.34 for
      mammography and AOR 1.39, 95% CI 1.06-1.81 for CBE). Also, adjusted lower
      likelihood of CBE attendance was predicted by younger age, higher religiosity,
      and higher social barriers. Differences in screening behaviors of younger and
      older Arab women from the West Bank and from Israel represent a traditional
      westernizing continuum of change, but are also related to the social and
      situational context.

PMID- 21191649
TI  - P53 genotype as a determinant of ER expression and tamoxifen response in the MMTV
      Wnt-1 model of mammary carcinogenesis.
AB  - Clinical studies show that estrogen receptor-alpha (ER) expressing tumors tend to
      have better prognosis, respond to antiestrogen therapy and have wild-type p53.
      Conversely, tumors with inactivating mutations in p53 tend to have worse outcomes
      and to be ER-negative and unresponsive to antihormone treatment. Previous studies
      from our laboratory have shown that p53 regulates ER expression
      transcriptionally, by binding the ER promoter and forming a complex with CARM1,
      CBP, c-Jun, RNA polymerase II and Sp1. In this study, the MMTV-Wnt-1 transgenic
      mouse model was used to demonstrate that p53 regulation of ER expression and
      function is not solely an in vitro phenomenon, but it is also operational in
      mammary tumorigenesis in vivo. The expression of ER and the ability to respond to
      tamoxifen were determined in mammary tumors arising in p53 wild type (WT) or p53
      heterozygous (HT) animals carrying the Wnt-1 transgene. In p53 WT mice,
      development of ER-positive tumors was delayed by tamoxifen treatment, while
      tumors arising in p53 HT mice had significantly reduced levels of ER and were not
      affected by tamoxifen. P53 null tumors were also found in the p53 HT mice and
      these tumors were ER-negative. ER expression was upregulated in mouse mammary
      tumor cell lines following transfection with WT p53 or treatment with
      doxorubicin. These data demonstrate that p53 regulates ER expression in vivo, and
      affects response to tamoxifen. Results also provide an explanation for the
      concordant relationship between these prognostic proteins in human breast tumors.

PMID- 21191650
TI  - The vagus nerve and autonomic imbalance in heart failure: past, present, and
      future.

PMID- 21191651
TI  - Hippocampal gene network analysis in an experimental model of posttraumatic
      epilepsy.
AB  - In the present study, we performed comprehensive gene expression and gene network
      analyses using a DNA microarray to elucidate the molecular events responsible for
      the pathology of posttraumatic epilepsy at the partial seizure stage. We used an
      experimental posttraumatic epilepsy model of amygdalar focal FeCl(3)-injected
      rats and compared gene expression profiles in the hippocampus at the partial
      seizure stage (less than stage 3 on Racine's convulsion scale) and that of sham
      operated animals. At the partial seizure stage, upregulation of phospholipase A2
      (PLA2) and lipid metabolism were observed, which have been reported to be caused
      by brain injury and seizures in previous studies. Furthermore, significant
      upregulation of genes related to inflammation and the immune system was observed.
      These molecular changes in PLA2 and lipid metabolism may be related to seizure
      propagation.

PMID- 21191652
TI  - Rostrocaudal dynamics of CSF biomarkers.
AB  - The rostrocaudal gradient (RCG) of markers present in cerebrospinal fluid (CSF)
      has not been studied adequately due to lack of appropriate control populations
      and ethical restrictions. The aim of this study is to understand the rostrocaudal
      gradient of CSF biomarkers. We contacted a study comparing CSF levels of seven
      biomarkers from cisternal (rostral) and lumbar (caudal) CSF obtained from
      patients with trigeminal neuralgia and tension-type headache. The RCGs of
      CSF/serum albumin ratio, 8-isoprostane. GFAP, total tau and beta amyloid protein
      were higher than one. The RCGs of lactate, VEGF and the heavy chain of
      neurofilament protein were lower than one. The study provides new values for
      several commonly examined markers of cisternal CSF. Knowledge of the RCG gradient
      of different CSF markers is important in interpreting studies reporting
      ventricular CSF values.

PMID- 21191653
TI  - Proportional hazards regression with interval censored data using an inverse
      probability weight.
AB  - The prevalence of interval censored data is increasing in medical studies due to
      the growing use of biomarkers to define a disease progression endpoint. Interval
      censoring results from periodic monitoring of the progression status. For
      example, disease progression is established in the interval between the clinic
      visit where progression is recorded and the prior clinic visit where there was no
      evidence of disease progression. A methodology is proposed for estimation and
      inference on the regression coefficients in the Cox proportional hazards model
      with interval censored data. The methodology is based on estimating equations and
      uses an inverse probability weight to select event time pairs where the ordering
      is unambiguous. Simulations are performed to examine the finite sample properties
      of the estimate and a colon cancer data set is used to demonstrate its
      performance relative to the conventional partial likelihood estimate that ignores
      the interval censoring.

PMID- 21191654
TI  - Evaluation of phenotypic and PCR-based approaches for routine analysis of
      Bacillus cereus group foodborne isolates.
AB  - Identification of Bacillus cereus sensu stricto is a challenge for the food
      industry since it is being increasingly reported as implicated in many foodborne
      outbreaks. So far no conclusive microbiological or biochemical traits have been
      described for their specific differentiation. Here a polyphasic approach aiming
      at identification of new isolates is presented. It was conducted on a total of 75
      strains, 59 Bacillus cereus group (29 reference strains and 30 food and
      environmental isolates) and 16 other Bacillus species. It includes biochemical
      traits (API 50CH and API 20E) and genetic profiles: PCR amplification of the
      internal spacer region (ISR) between 23S and 16S rRNA genes (ISR-PCR), randomly
      amplified polymorphic DNA (RAPD-PCR) with three universal primers (M13, T3, and
      T7), and PCR amplification using specific primers directed to genes encoding
      hemolysin BL (hbl), cytotoxin K (cytK) and cereulide (ces). As expected, PCR
      enterotoxin profiles revealed the toxigenic potential of strains within the B.
      cereus group irrespective of the species. Cluster analysis combining the three
      RAPD fingerprints (RAPD-M13, RAPD-T3 and RAPD-T7) allowed almost a complete
      separation of strains within the B. cereus group. As a result, the ISR-PCR
      profile is proposed for the rapid assignation of isolates to B. cereus group with
      the advantage over the API profile of being a specific and culture-independent
      technique. Following, differentiation at species level can be obtained by RAPD
      profiles analysis.

PMID- 21191655
TI  - Visual impairment and health-related quality of life among elderly adults with
      age-related eye diseases.
AB  - PURPOSE: To examine the association between age-related eye disease (ARED),
      visual impairment, and health-related quality of life (HRQOL). METHODS: We used
      data from the 2006 and 2008 Behavioral Risk Factor Surveillance System to examine
      self-reported visual impairment and two HRQOL domains-physical impairment
      (including poor general health, physical unhealthy days, activity-limitation
      days, and disability) and mental distress (including mental unhealthy days, life
      dissatisfaction, major depression, lifetime depression, and anxiety) for people
      aged 65 years or older, by ARED status. RESULTS: People with any ARED were more
      likely than those without to report visual impairment as well as physical
      impairment and mental distress. The prevalence of visual impairment (P trend
      <0.001) and physical impairment (P trend <0.001) increased with increasing number
      of eye diseases after controlling for all covariates. There was no significant
      linear trend, however, in mental distress among people with one or more eye
      diseases. CONCLUSION: ARED was found to be associated with visual impairment and
      poorer HRQOL. Increasing numbers of AREDs were associated with increased levels
      of visual impairment and physical impairment, but were not associated with levels
      of mental distress.

PMID- 21191656
TI  - Respiratory events in preterm infants prior to discharge: with and without
      clinically concerning apnoea.
AB  - PURPOSE: This study aimed to determine the characteristics of respiratory events
      in preterm infants with clinically concerning apnoea at or beyond 35 weeks
      postmenstrual age and to compare these findings with a group of preterm infants
      ready for discharge, without clinically concerning apnoea. METHODS: Infants born
      at <32 weeks of gestation and who underwent nap polysomnography at or beyond 35
      weeks corrected age prior to discharge were included. Cases were preterm infants
      with clinically concerning apnoea, and control infants were preterm infants
      asymptomatic for apnoea. Infants with upper airway obstruction, congenital
      malformations or apnoea associated with sepsis were excluded. Studies were
      retrospectively reviewed for length, type and frequency of apnoea. The
      relationship between sleep state and changes in oxygen saturation was compared
      between groups. Peri-natal and demographic data were also compared. RESULTS: Data
      were complete for 16 case and 18 control infants. Gestational age was similar at
      birth and at time of study, but cases had a lower birth weight (p = 0.04) and
      higher weight at study (p = 0.04). There were no group differences in the mean
      duration, type or numbers of apnoea. The duration of the longest apnoea was
      greater in case infants (17.4 s vs. 12.3 s, p = 0.02). Lowest oxygen saturation
      (p < 0.05) and average minimum oxygen saturation (p < 0.05) were lower in case
      infants. CONCLUSIONS: Preterm infants with clinically concerning apnoea have
      similar amounts and types of apnoea but lower oxygen saturation after apnoea
      compared with controls. The use of oxygen saturation monitoring is more useful
      than respiratory monitoring alone in recognising these events.

PMID- 21191657
TI  - Novel observations during extracorporeal membrane oxygenation in patients with
      ARDS due to the H1N1 pandemic influenza.
AB  - We report four patients with novel observations during extracorporeal membrane
      oxygenation support (ECMO). ECMO was initiated because of severe ARDS due to the
      primary H1N1 pandemic influenza pneumonia. Two patients had excessive conjugated
      hyperbilirubinemia and two had unproportional depletion of the coagulation factor
      IX. Pathogenetic mechanisms and clinical relevance of the noticed phenomena are
      discussed.

PMID- 21191659
TI  - Achalasia mimicking lung abscess.

PMID- 21191658
TI  - Pelvic organ function and quality of life after anastomotic leakage following
      rectal cancer surgery.
AB  - INTRODUCTION: There is a paucity of studies assessing the influence of
      anastomotic leakage after rectal cancer surgery on pelvic organ function and
      quality of life. METHODS: Between 1995 and 2006, 500 patients underwent rectal
      resection for malignancies at a single institution. Thirty-six patients (7.2%)
      developed an anastomotic leakage postoperatively. Fifteen of these patients
      (41.6%) died during the follow-up period. A self-administering questionnaire
      including the International Index of Erectile Function, Female Sexual Function
      Index, Short Form-12 Health Survey, International Prostatic Symptom Score,
      International Consultation on Incontinence Questionnaire-Short Form, Vaizey
      Incontinence Score and Wexner Constipation Score was sent to all 21 alive
      patients. Patients with rectal cancer resection without leakage served as
      controls for each case and were matched by sex, age (+/-5 years), type of
      resection, and neoadjuvant therapy (yes/no). RESULTS: Sixteen patients (76.2%)
      were available and were included in the analysis. The median follow-up time was
      106.8 months (32.4-170.4). Fecal incontinence, constipation, and sexual function
      did not differ significantly between patients and controls (p = 0.1973, 0.1189,
      0.8519, respectively). By contrast, urinary continence was impaired significantly
      in the leakage group (p = 0.0430) but not in control patients. The Quality of
      Life assessing Short Form-12 Health Survey reached no significant difference
      between both groups (p = 1.0000 and 0.1973). CONCLUSION: Anastomotic leakage
      following anterior resection negatively aggravates urinary function but not fecal
      incontinence, constipation or sexual functions. The data indicate that patients
      experiencing anastomotic leakages can be relieved from the fear of gross pelvic
      floor function disturbances.

PMID- 21191660
TI  - Still present after all these years: persistence plus potential toxicity raise
      questions about the use of atrazine.
AB  - As one of the worlds' most heavily applied herbicides, atrazine is still a matter
      of controversy. Since it is regularly found in ground and drinking water, as well
      as in sea water and the ice of remote areas, it has become the subject of
      continuous concern due to its potential endocrine and carcinogenic activity.
      Current findings prove long-held suspicions that this compound persists for
      decades in soil. Due to the high amount applied annually all over the world, the
      soil burden of this compound is considered to be tremendous, representing a
      potential long-term threat to the environment. The persistence of chemicals such
      as atrazine has long been underestimated: Do we need to reconsider the
      environmental risk?

PMID- 21191661
TI  - A hybrid strategy to integrate surface-based and mutual-information-based methods
      for co-registering brain SPECT and MR images.
AB  - Co-registration of brain SPECT and MR images has been used extensively in
      clinical applications. The complementary features of two major co-registration
      methods--surface- and mutual-information-based (MI-based)--motivated us to study
      a hybrid-based scheme that uses the surface-based method to achieve a quick
      alignment, followed by the MI-based method for fine tuning. Computer simulations
      were conducted to evaluate the accuracy and robustness of surface-, MI-, and
      hybrid-based registration methods by designing different levels of noise and
      mismatch in the registration experiments. Results demonstrated that the hybrid
      surface-MI-based scheme outperforms both the surface- and MI-based methods in
      providing superior accuracy and success rates. Specifically, the translational
      and rotational errors were no more than 1 mm and 2 degrees , respectively, with
      consistent success rates over 98%. Besides, the hybrid-based method saved 12-53%
      of the computation efforts, compared with using the MI-based method alone. We
      recommend the use of hybrid-based method when the orientational differences
      between the floating and reference images exceed 10 degrees .

PMID- 21191662
TI  - Bards, poets, and cliques: frequency-dependent selection and the evolution of
      language genes.
AB  - The ability of humans to communicate via language is a complex, adapted
      phenotype, which undoubtedly has a recently evolved genetic component. However,
      the evolutionary dynamics of language-associated alleles are poorly understood.
      To improve our knowledge of such systems, a population-genetics model for
      language-associated genes is developed. (The model is general and applicable to
      social interactions other than communication.) When an allele arises that
      potentially improves the ability of individuals to communicate, it will
      experience positive frequency-dependent selection because its fitness will depend
      on how many other individuals communicate the same way. Consequently, new and
      rare alleles are selected against, posing a problem for the evolutionary origin
      of language. However, the model shows that if individuals form language-based
      cliques, then novel language-associated alleles can sweep through a population.
      Thus, the origin of language ability can be sufficiently explained by Darwinian
      processes operating on genetic diversity in a finite population of human
      ancestors.

PMID- 21191663
TI  - Bistability analysis of an apoptosis model in the presence of nitric oxide.
AB  - Bistability in apoptosis, or programmed cell death, is crucial for the healthy
      functioning of multicellular organisms. The aim in this study is to show the
      presence of bistability in a mitochondria-dependent apoptosis model under nitric
      oxide effects using chemical reaction network theory. The model equations are a
      set of coupled ordinary differential equations arising from the assumed mass
      action kinetics. Whether these equations have a capacity for bistability (cell
      survival and apoptosis) is determined using a modular approach in which the model
      is decomposed into modules. Each module contains only a subset of the whole model
      and is analyzed separately. It is seen that bistability in a module is preserved
      throughout the whole model after adding the remaining reactions in the pathway on
      these modules. It is also found that inhibitor effect of some proteins and the
      appearance of a reacting protein in a later stage as a product is a desired
      feature but not sufficient for bistability (in the absence of cooperativity
      effects). On the whole model, two apoptotic and two cell survival states are
      obtained depending on the initial cell conditions. The results suggest that the
      antiapoptotic effects of nitric oxide species are responsible for the bistable
      character of the apoptotic pathway when cooperativity is not assumed in the
      apoptosome formation.

PMID- 21191664
TI  - Lessons from nature for preservation of mammalian cells, tissues, and organs.
AB  - The study of mechanisms by which animals tolerate environmental extremes may
      provide strategies for preservation of living mammalian materials. Animals employ
      a variety of compounds to enhance their survival, including production of
      disaccharides, glycerol, and antifreeze compounds. The cryoprotectant glycerol
      was discovered before its role in amphibian survival. In the last decade,
      trehalose has made an impact on freezing and drying methods for mammalian cells.
      Investigation of disaccharides was stimulated by the variety of organisms that
      tolerate dehydration stress by accumulation of disaccharides. Several methods
      have been developed for the loading of trehalose into mammalian cells, including
      inducing membrane lipid-phase transitions, genetically engineered pores,
      endocytosis, and prolonged cell culture with trehalose. In contrast, the many
      antifreeze proteins (AFPs) identified in a variety of organisms have had little
      impact. The first AFPs to be discovered were found in cold water fish; their AFPs
      have not found a medical application. Insect AFPs function by similar mechanisms,
      but they are more active and recombinant AFPs may offer the best opportunity for
      success in medical applications. For example, in contrast to fish AFPs,
      transgenic organisms expressing insect AFPs exhibit reduced ice nucleation.
      However, we must remember that nature's survival strategies may include
      production of AFPs, antifreeze glycolipids, ice nucleators, polyols,
      disaccharides, depletion of ice nucleators, and partial desiccation in synchrony
      with the onset of winter. We anticipate that it is only by combining several
      natural low temperature survival strategies that the full potential benefits for
      mammalian cell survival and medical applications can be achieved.

PMID- 21191665
TI  - microRNAs at the regulatory frontier: an investigation into how microRNAs impact
      the development and effector functions of CD4 T cells.
AB  - CD4 T cells are an integral part of adaptive immunity. microRNAs have been
      identified as fundamental regulators of post-transcriptional programs and to play
      roles in T lymphocytes' development, differentiation, and effector functions. To
      better understand the role of miRNAs in T cells and to identify potential
      therapeutic tools and targets, we have undertaken studies of miRNAs that modulate
      or are modulated by T-cell receptor signaling. We identified miR-181a as a key
      regulator of TCR signaling strength, and hence T-cell development, and the miR-17
      92 cluster as an important player in CD4 T cells' response against antigens.
      These discoveries, coupled with work by other researchers, reveal the power and
      importance of miRNA-mediated regulation in T-cell responses and offer new
      insights into the burgeoning field of immunoregulation.

PMID- 21191667
TI  - Response to temozolomide and bevacizumab in a patient with poorly differentiated
      neuroendocrine carcinoma.
AB  - Poorly differentiated endocrine carcinomas (PDEC) are usually treated with
      cisplatin-based chemotherapy regimens. We here present a case with a dramatic
      response (both radiologically and biochemically) to the combination of
      temozolomide and bevacizumab, after failure of cisplatin and etoposide, with
      continued tumor shrinkage at 5 months. Temozolomide combined with bevacizumab
      might be a good treatment option in PDEC, perhaps even in a first-line setting.
      Prospective studies to answer this are warranted.

PMID- 21191666
TI  - Cutting edge issues in polymyositis.
AB  - Skeletal muscle is the target tissue of immunoflogistic processes in patients
      affected with idiopathic inflammatory myopathies (IIM). IIM are classified into
      three major forms: polymyositis (PM), dermatomyositis (DM), and inclusion body
      myositis. Recent data suggest that, in the major subsets of myositis, antigens in
      muscles drive a B-cell antigen-specific immune response. Moreover, some non
      immunological mechanisms have been advocated. In this regard, an increased
      expression of Jo-1 and Mi-2 in muscle biopsies from PM and DM patients compared
      to normal muscle has been demonstrated; these candidate autoantigens in myositis
      are expressed at high levels in regenerating muscle cells rather than in mature
      myotubes. Myositis autoantigen upregulation has also been observed in neoplastic
      tissues, thus representing a potential link between cancer and autoimmunity in
      myositis. Myositis-specific autoantibodies (MSA) are disease markers and target
      intracellular proteins involved in key processes such as translocation and
      nuclear transcription. Myositis target antigens encompass aminoacyl-tRNA
      synthetases, the Mi-2 helicase/histone deacetylase protein complex, the signal
      recognition particle ribonucleoprotein, together with novel target antigens
      including p155/140, CADM-140, and SAE. Despite their high specificity for
      autoimmune myositis, MSA target non-muscle restricted proteins ubiquitary to all
      cell types, making the specific muscle involvement difficult to explain. Non
      immunological mechanisms also seem to contribute to the pathogenesis of IIM;
      activation of endoplasmic reticulum stress response due to muscle regeneration
      and inflammation but independent to MHC-1 up-regulation has been recently
      reported in patients with myositis.

PMID- 21191668
TI  - The rare-earth yttrium complex [YR(mtbmp)(thf)] triggers apoptosis via the
      extrinsic pathway and overcomes multiple drug resistance in leukemic cells.
AB  - A major problem in treating patients with acute lymphoblastic leukemia is the
      development of drug resistance. In the current study, we investigated the
      anticancer properties of the novel rare-earth yttrium complex [YR(mtbmp)(thf)] in
      various established cell lines, and moreover, we identified the involved
      apoptotic pathway. Further aim was to investigate whether synergistic effects
      could be reached in combination with the conventional drug vincristine. We used
      the yttrium complex [YR(mtbmp)(thf)] in cells of leukemia (Nalm-6) and lymphoma
      (BJAB) and identified the main mechanism of the apoptosis induction by measuring
      the amount of hypodiploid DNA via FACS Scan analysis. Exposure of BJAB cells to
      [YR(mtbmp)(thf)] led to a death receptor-mediated reduction of cell viability and
      induction of apoptosis. The independence of Bcl-2 expression supports the
      suggestion that the [YR(mtbmp)(thf)]-induced apoptosis is mainly mediated via the
      extrinsic pathway. The extensive anti-tumor activity of [YR(mtbmp)(thf)] could be
      underlined by its capability to overcome multiple drug resistance in leukemic
      cells (Nalm-6) that are characterized by an overexpression of P-glycoprotein.
      [YR(mtbmp)(thf)] in combination with the conventional drug vincristine displayed
      impressive synergistic effects. We demonstrate in vitro efficiency of
      [YR(mtbmp)(thf)] in cells of hematological malignancies and reveal its ability to
      be a possible agent for polychemotherapy.

PMID- 21191670
TI  - Interleukin-8 is associated with adhesion, migration and invasion in human
      gastric cancer SCG-7901 cells.
AB  - Interleukin-8 is known as an important chemokine involved in tumor angiogenesis
      and progression. Overexpression of interleukin-8 has been detected in a variety
      of human tumors, including gastric cancer, and is negatively correlated with
      prognosis. The aim of our study is to determine the effects of interleukin-8 on
      proliferation, adhesion, migration and invasion abilities and correlated
      molecular mechanisms in gastric cancer. We made recombinant interleukin-8 ranged
      from 0 ng/ml to 100 ng/ml interferes in human gastric cancer SCG-7901 cells in
      vitro. The results shown that interleukin-8 did not change cell proliferation,
      but promoted cell adhesion to endothelial cell and extracellular matrix
      components (collagen, laminin and fibronectin) as detected by Cell Counting Kit
      8. And it induced migration and invasion ability based on scratch and transwell
      chamber assays. Also, interleukin-8 regulated the protein and mRNA expression of
      matrix metalloproteinase-9, intercellular adhesion molecule-1 and E-cad and there
      was obviously a dose-dependent relationship, but the protein or mRNA expression
      of matrix metalloproteinase-2 was not obviously changed under the tested
      conditions. Our findings indicate that interleukin-8 is associated with adhesion,
      migration and invasion in gastric cancer and the regulation of matrix
      metalloproteinase-9, intercellular adhesion molecule-1 and E-cad expression is
      one of the potential molecule mechanisms. The studies imply interleukin-8 may be
      an alternative treatment strategy against gastric cancer.

PMID- 21191669
TI  - Role of Na+/H+ exchanger in resveratrol-induced growth inhibition of human breast
      cancer cells.
AB  - Cancer cells maintain low intracellular pH [pHi]; therefore, it is likely that
      resveratrol [RSVL] inhibits cell growth through interference with regulation of
      pHi. Na-H exchanger [NHE] regulates pHi and NaCl uptake. In this study, we
      investigated a putative role of NHE-1 and NHE-3 isoforms in the RSVL-induced cell
      death using MDA-MB-231 estrogen receptor-negative [ER-] and MCF-7 [ER+] human
      breast cancer cell lines. ECL Western blot analysis and fluorescence
      morphometeric analysis were used. Cell viability and counting were performed
      using standard procedures. RSVL caused a dose- and time-dependent induction of
      NHE-1 and NHE-3 proteins in both cancer cell lines as shown by ECL Western blot
      analysis and fluorescence measurement. Interestingly, the level of actin, an
      internal control, remains unaltered. Thus, it is concluded that RSVL-inhibited
      cell growth and viability, increased cell size, and volume along with an
      increased apoptotic activity are due to the induction of NHE-1 and NHE-3 isoforms
      in the present breast cancer cell lines. Induction of NHE will increase the
      uptake of NaCl and decrease pHi leading to disturbance in Ca(2+) homeostasis,
      which is responsible for cell death.

PMID- 21191671
TI  - Ursolic acid induces apoptosis by suppressing the expression of FoxM1 in MCF-7
      human breast cancer cells.
AB  - Ursolic acid (UA), a naturally occurring pentacyclic triterpene, is a potent in
      vitro anticancer agent, acting through control of growth, apoptosis, and
      differentiation. As the anticancer effect and the mechanism of action of ursolic
      acid on human breast cancer cells has not been extensively studied, we performed
      an evaluation of the effects of UA on apoptosis in MCF-7 cells. UA was found to
      inhibit the proliferation of MCF-7 cells in a concentration and time-dependent
      manner. After treatment, UA-induced apoptosis was accompanied by a significant
      decrease in CyclinD1/CDK4 expression, which can be regulated by FoxM1. Previous
      studies demonstrated that FoxM1 orchestrates the transcription of genes that are
      essential for cell cycle progression and cell proliferation. The result of
      Western blot suggested that ursolic acid inhibited the expression of FoxM1. Taken
      together, the data suggest that the proapoptotic effect of UA on MCF-7 cells is
      mediated by inhibition of FoxM1 and is highly correlated with inactivation of
      CyclinD1/CDK4.

PMID- 21191672
TI  - Prevention of iron deficiency anemia (IDA): how far have we reached?
AB  - Anemia is a global problem of immense public health significance. Iron deficiency
      anemia is the most common nutritional disorder seen all over the world, more in
      the developing countries, particularly, affecting young children of 6-24 months
      of age, adolescents, women of reproductive age group and pregnant/ lactating
      women. Basic approach in prevention of IDA should include education and
      associated measures to increase the dietary intake of iron, dietary modification
      to enhance the iron absorption, fortification of food articles, in addition to
      control the infection and worm infestations. Supplemenldelim 1, of medicinal iron
      is key to success which can be achieved by daily or intermittent
      (biweekly/weekly) administration of oral iron to the target group. Reduction of
      nutritional anemia should receive top priority through proper planning by using
      better utilization of existing health infrastructure.

PMID- 21191673
TI  - Pathogenesis of HIV in the central nervous system.
AB  - HIV can infect the brain and impair central nervous system (CNS) function.
      Combination antiretroviral therapy (cART) has not eradicated CNS complications.
      HIV-associated neurocognitive disorders (HAND) remain common despite cART,
      although attenuated in severity. This may result from a combination of factors
      including inadequate treatment of HIV reservoirs such as circulating monocytes
      and glia, decreased effectiveness of cART in CNS, concurrent illnesses, stimulant
      use, and factors associated with prescribed drugs, including antiretrovirals.
      This review highlights recent investigations of HIV-related CNS injury with
      emphasis on cART-era neuropathological mechanisms in the context of both US and
      international settings.

PMID- 21191674
TI  - The role of anxiety and emotional stress as a risk factor in treatment-resistant
      hypertension.
AB  - Depression and anxiety are both known to be co-morbid with coronary heart
      disease. Given the high prevalence of coronary heart disease today, specifically
      the aspect of hypertension, it seems more important than ever to investigate
      whether or not treatment of these co-morbidities can have an effect on reducing
      hypertension. This article summarizes the limited amount of literature that has
      been published in this area and highlights what we believe to be a missing key
      element that will guide our own future research in this area.

PMID- 21191675
TI  - Burkitt lymphoma and atypical Burkitt or Burkitt-like lymphoma: should these be
      treated as different diseases?
AB  - Burkitt lymphoma (BL) is a mature B-cell non-Hodgkin lymphoma with an aggressive
      clinical course. Since the advent of short, intensive, multiagent
      chemoimmunotherapy regimens, it has carried a favorable prognosis. BL has been
      rather well characterized, whereas the other lymphomas morphologically resembling
      it are more heterogeneous. The cases classified as atypical BL/Burkitt-like
      lymphoma by the 2001 World Health Organization (WHO) Classification of Tumors of
      Hematopoietic and Lymphoid Tissue were thought to represent a continuum between
      BL and diffuse large B-cell lymphoma (DLBCL). The optimal therapeutic strategy
      for this provisional entity was not definitively established. However, recent
      incorporation of molecular genetic data into the 2008 WHO Classification has
      allowed further refinements with significant therapeutic implications, including
      the designation of a new provisional entity, "B-cell lymphoma, unclassifiable,
      with features intermediate between BL and DLBCL." This review presents a
      comprehensive overview of the previously designated provisional entity of
      atypical BL/BLL in conjunction with a detailed comparison with BL and DLBCL.

PMID- 21191676
TI  - Physicochemical characterization of NPC 1161C, a novel antimalarial 8
      aminoquinoline, in solution and solid state.
AB  - NPC 1161C is a novel antimalarial drug of interest because of its superior
      curative and prophylactic activity, and favorable toxicity profile against in
      vivo and in vitro models of malaria, pneumocystis carinii pneumonia, and
      leishmaniasis. The preformulation studies performed included determination of
      pK(a)s, aqueous and pH solubility, cosolvent solubility, log P, pH stability,
      thermal analysis, and preliminary hygroscopicity studies. The mean pK(a1),
      pK(a2), and pK(a3) were determined to be 10.12, 4.07, and 1.88, respectively. The
      aqueous solubility was found to be 2.4*10(-4) M having a saturated solution pH of
      4.3-5.0 and a low intrinsic solubility of 1.6*10(-6) M. A mathematical model of
      the pH-solubility profile was derived from pH 2.2 to 8.0. An exponential decrease
      in solubility was observed with increasing pH. The excess solid phase in
      equilibrium with the solution in aqueous buffers was determined to be the free
      base form of the drug. A significant increase in solubility was observed with all
      the cosolvents studied, in both unbuffered and buffered systems. Mean log P of
      the salt and the free base were estimated to be 2.18 and 3.70, respectively. The
      compound had poor stability at pH 7.0 at 37  degrees C, with a t (90) of 3.58
      days. Thermal analysis of the drug using DSC and TGA revealed that the drug is
      present as a semi-crystalline powder, which transformed into the amorphous state
      after melting. The drug was also found to sublime at higher temperatures.
      Determination of physicochemical properties of NPC 1161C provided useful
      information for the development of a dosage form and preclinical evaluation.

PMID- 21191677
TI  - Biochemical modulation of aracytidine (Ara-C) effects by GTI-2040, a
      ribonucleotide reductase inhibitor, in K562 human leukemia cells.
AB  - GTI-2040 is a potent antisense to the M2 subunit of the ribonucleotide reductase
      (RNR), an enzyme involved in the de novo synthesis of nucleoside triphosphates.
      We hypothesized that combination of GTI-2040 with the cytarabine (Ara-C) could
      result in an enhanced cytotoxic effect with perturbed intracellular
      deoxynucleotide/nucleotide (dNTP/NTP) pools including Ara-C triphosphate (Ara
      CTP). This study aims to provide a direct experimental support of this hypothesis
      by monitoring the biochemical modulation effects, intracellular levels of Ara
      CTP, dNTPs/NTPs following the combination treatment of Ara-C, and GTI-2040 in
      K562 human leukemia cells. GTI-2040 was introduced into cells via
      electroporation. A hybridization-ligation ELISA was used to quantify
      intracellular GTI-2040 concentrations. Real-time PCR and Western blot methods
      were used to measure the RNR M2 mRNA and protein levels, respectively. 3-(4,5
      Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H
      tetrazolium, inner salt assay was used to measure the cytotoxicity following
      various drug treatments. A non-radioactive HPLC-UV method was used for measuring
      the intracellular Ara-CTP, while a LC-MS/MS method was used to quantify
      intracellular dNTP/NTP pools. GTI-2040 was found to downregulate M2 mRNA and
      protein levels in a dose-dependent manner and showed significant decrease in dNTP
      but not NTP pool. When combining GTI-2040 with Ara-C, a synergistic cytotoxicity
      was observed with no further change in dNTP/NTP pools. Importantly, pretreatment
      of K562 cells with GTI-2040 was found to increase Ara-CTP level for the first
      time, and this effect may be due to inhibition of RNR by GTI-2040. This finding
      provides a laboratory justification for the current phase I/II evaluation of GTI
      2040 in combination with Ara-C in patients with acute myeloid leukemia.

PMID- 21191679
TI  - c-Jun N-terminal kinase (JNK) and p38 play different roles in age-related
      Purkinje cell death in murine organotypic culture.
AB  - Several studies have shown that Purkinje cells die by apoptosis in organotypic
      slice cultures from postnatal 3-day-old (P3) mice. This cell death is age
      dependent and has been proposed as indirect evidence for the programmed Purkinje
      cell death occurring in in vivo cerebellum. Here, we studied whether c-jun N
      terminal kinase (JNK) and p38 kinase pathways contribute to the Purkinje cell
      death observed in cerebellar slice cultures obtained from P3 mice. Slice culture
      treatment with D-JNKI1 or SB203580, respectively inhibitors of JNK and p38 MAP
      kinases, results in a better survival of Purkinje cells. Interestingly, the
      combined treatment with the two inhibitors potentiated single treatment effects.
      These results suggest that p38 and JNK pathways might be differently implicated
      in this Purkinje cell death. Time course experiments found p38 activation
      immediately post-slicing, whereas JNK activation was detected only 2 h after the
      culture. We hypothesize that p38 activation might be due to the "sliced
      condition," and JNK activation might be more specific to P3 age-dependent cell
      death. The study of JNK and p38 activation in cerebellar lysates from P0 slice
      culture confirmed JNK activation being specific for the P3 explants, whereas p38
      is activated both from P0 and P3 cerebellar slice culture lysates. These results
      suggest that p38 is activated by the slicing, whereas JNK activation is related
      to developmental Purkinje cell death.

PMID- 21191678
TI  - Plasmodium falciparum encodes a single cytosolic type I Hsp40 that functionally
      interacts with Hsp70 and is upregulated by heat shock.
AB  - Heat shock protein 70 (Hsp70) and heat shock protein 40 (Hsp40) function as
      molecular chaperones during the folding and trafficking of proteins within most
      cell types. However, the Hsp70-Hsp40 chaperone partnerships within the malaria
      parasite, Plasmodium falciparum, have not been elucidated. Only one of the 43 P.
      falciparum Hsp40s is predicted to be a cytosolic, canonical Hsp40 (termed
      PfHsp40) capable of interacting with the major cytosolic P. falciparum-encoded
      Hsp70, PfHsp70. Consistent with this hypothesis, we found that PfHsp40 is
      upregulated under heat shock conditions in a similar pattern to PfHsp70. In
      addition, PfHsp70 and PfHsp40 reside mainly in the parasite cytosol, as assessed
      using indirect immunofluorescence microscopy. Recombinant PfHsp40 stimulated the
      ATP hydrolytic rates of both PfHsp70 and human Hsp70 similar to other canonical
      Hsp40s of yeast (Ydj1) and human (Hdj2) origin. In contrast, the Hsp40-stimulated
      plasmodial and human Hsp70 ATPase activities were differentially inhibited in the
      presence of pyrimidinone-based small molecule modulators. To further probe the
      chaperone properties of PfHsp40, protein aggregation suppression assays were
      conducted. PfHsp40 alone suppressed protein aggregation, and cooperated with
      PfHsp70 to suppress aggregation. Together, these data represent the first
      cellular and biochemical evidence for a PfHsp70-PfHsp40 partnership in the
      malaria parasite, and furthermore that the plasmodial and human Hsp70-Hsp40
      chaperones possess unique attributes that are differentially modulated by small
      molecules.

PMID- 21191680
TI  - Guidelines to the Practice of Anesthesia: Revised edition 2011.
AB  - The Guidelines to the Practice of Anesthesia Revised Edition 2011 (the
      guidelines) were prepared by the Canadian Anesthesiologists' Society (CAS), which
      reserves the right to determine their publication and distribution. Because the
      guidelines are subject to revision, updated versions are published annually.
      Whereas previous versions of the guidelines appeared as special supplements to
      the Canadian Journal of Anesthesia (the Journal), this edition of the guidelines
      is published within the Journal. This allows for improved archiving and online
      access to complement the printed version-a new offering for CAS members and
      Journal subscribers. The Guidelines to the Practice of Anesthesia Revised Edition
      2011 supersedes all previously published versions of this document. Although the
      CAS encourages Canadian anesthesiologists to adhere to its practice guidelines to
      ensure high-quality patient care, the society cannot guarantee any specific
      patient outcome. Each anesthesiologist should exercise his or her own
      professional judgement in determining the proper course of action for any
      patient's circumstances. The CAS assumes no responsibility or liability for any
      error or omission arising from the use of any information contained in its
      Guidelines to the Practice of Anesthesia.

PMID- 21191681
TI  - Nonalcoholic fatty liver disease in India - a lot done, yet more required!
AB  - Nonalcoholic fatty liver disease (NAFLD) is emerging as an important cause of
      liver disease in India. Epidemiological studies suggest prevalence of NAFLD in
      around 9% to 32% of general population in India with higher prevalence in those
      with overweight or obesity and those with diabetes or prediabetes.
      Clinicopathological studies show that NAFLD is an important cause of unexplained
      rise in hepatic transaminases, cryptogenic cirrhosis and cryptogenic
      hepatocellular carcinoma in Indian patients. There is high prevalence of insulin
      resistance and nearly half of Indian patients with NAFLD have evidence of full
      blown metabolic syndrome. Though oxidative stress is involved in the pathogenesis
      of NAFLD/nonalcoholic steatohepatitis, serum or liver iron and HFE gene mutations
      appear not to play a role in the pathogenesis of NAFLD in Indian patients.
      Imaging modalities are not useful in differentiating simple steatosis from NASH
      and liver biopsy may be useful in those with risk factors for significant liver
      disease. Pilot studies on treatment strategies have shown that weight reduction
      and exercise, ursodeoxycholic acid, metformin, vitamin E and pentoxyfylline are
      effective in normalizing transaminases and or in improving hepatic steatosis and
      inflammation in Indian patients with NAFLD. Randomized controlled treatment
      trials involving large number of patients with histological end point are
      required to assess the efficacy of different modalities. In conclusion, a lot has
      been done, yet more is required to understand various aspects of NAFLD in India.

PMID- 21191682
TI  - Frequency of false positive amphetamine screens due to bupropion using the Syva
      EMIT II immunoassay.
AB  - Bupropion is a commonly prescribed, monocyclic antidepressant often used as an
      aid for smoking cessation. Several case reports have described false positive
      amphetamine urine drug screens (UDS) associated with bupropion. We sought to
      determine whether false positive amphetamine UDS due to the use of bupropion
      would be a frequent occurrence. We conducted an IRB-approved, retrospective chart
      review of all emergency department patients who underwent UDS between 1 January
      2006 and 31 July 2007. All urine samples were screened using Syva EMIT II Plus
      immunoassay reagents. All positive screens underwent confirmation by gas
      chromatography (GC). We reviewed the records of patients with positive
      amphetamine UDS. We documented prescription use of bupropion, other
      antidepressants, stimulants, antipsychotics, and anti-hypertensives. We recorded
      evidence of polysubstance abuse (PSA) as patients who had had a documented
      diagnosis or laboratory evidence of abuse of at least two substances (drugs or
      ethanol). Of 10,011 urine drug screens, 362 (3.6%) were positive for amphetamine.
      GC confirmed amphetamines in 234 (65%), but failed to confirm in 128 (35%). Among
      the 234 confirmed, records reflected use of bupropion in three (1.3%), other
      antidepressants in 38 (16%), antipsychotics in 17 (8%), and amphetamine in 50
      (21%). Records indicated evidence of PSA in 55 (24%). Among the 128 which failed
      to confirm, records reflected prescription use of bupropion in 53 (41%). None
      whose drug screen failed to confirm had evidence of PSA. Therapeutic use of
      bupropion appears to be the most frequent cause of false positive urine drug
      screens for amphetamines in our population.

PMID- 21191684
TI  - Submandibular salivary glands: influence on growth rate and life span in mice.
AB  - Submandibular glands accumulate a variety of growth factors, especially in male
      mice. Surgical excision of these glands (sialoadenectomy) results in alterations
      in several organs and systems including the liver, skin and reproductive system.
      We studied the life-long consequences of sialoadenectomy in male mice. Animals
      were operated at the age of 10 weeks. Thereafter, body weight and food and water
      intake were controlled until death. Few weeks after surgery, body weight was
      lower in sialoadenectomized than in control mice. The difference remained stable
      until the age of 80 weeks. In spite of the lower body weight, food intake was
      higher in sialoadenectomized mice than in controls. The first death of
      sialoadenectomized mice occurred 10 weeks earlier than that of the first control,
      and the initial death rate in sialoadenectomized mice was almost twice the rate
      in controls. After 100 weeks of life, the death rate increased in control mice,
      but suddenly decreased in sialoadenectomized mice. The consequence was that the
      mean life span of the last 25% surviving animals was 10 weeks longer in
      sialoadenectomized than in control mice. Autopsy examination suggests that the
      effect of sialoadenectomy on death rate may be the consequence of a contrasting
      effect on tumour growth. Our results indicate that submandibular glands, or
      rather the factors derived from these glands, have contrasting roles in tumour
      growth. At early ages they may be survival factors and protect tissues, whereas
      at later ages they may stimulate the growth of transformed cells.

PMID- 21191685
TI  - Embolectomy for acute pulmonary thromboembolism: from Trendelenburg's procedure
      to the contemporary surgical approach.
AB  - Acute pulmonary thromboembolism (APTE) is a potentially catastrophic event after
      surgery. We reviewed the literature on surgical pulmonary embolectomy to
      elucidate its place in emergency management. Although pulmonary embolectomy is
      invasive, prompt removal of the emboli decreases the right ventricular load and
      promotes quick recovery of cardiopulmonary function. Conversely, fibrinolytic
      therapy places additional burden on patients at risk of potential hemorrhagic
      complication. Surgical embolectomy is an effective procedure with a low risk of
      hemorrhage because anticoagulant therapy is needed for only a short time.

PMID- 21191686
TI  - Sinusoidal obstruction syndrome compromises liver regeneration in patients
      undergoing two-stage hepatectomy with portal vein embolization.
AB  - PURPOSE: Several factors have been reported to affect liver regeneration after
      portal vein embolization (PVE); however, the effect of sinusoidal obstruction
      syndrome (SOS) has not been evaluated. Therefore, we assessed the effect of SOS
      on liver regeneration after PVE in patients with multiple bilobar colorectal
      liver metastases scheduled to undergo two-stage hepatectomy (TSH) combined with
      PVE. METHODS: The subjects of this study were 78 patients prospectively scheduled
      to undergo TSH between December 1996 and August 2009. Archived formalin-fixed,
      paraffin-embedded nontumoral tissue samples were collected from the 1st- and 2nd
      stage hepatectomies in 42 and 45 patients, respectively, and SOS and
      steatohepatitis were diagnosed pathologically. We analyzed the
      clinicopathological variables affecting liver regeneration after PVE. RESULTS:
      Sinusoidal obstruction syndrome was diagnosed in 11 (26.2%) and 20 patients
      (44.4%) at the time of the 1st- and 2nd-stage hepatectomy, respectively. Patients
      with SOS at the 1st-stage hepatectomy had a significantly lower hypertrophy ratio
      of the future remnant liver (FRL) after PVE than patients without SOS (16.8 +/-
      24.0 vs 55.6 +/- 32.5; P < 0.001). Multivariate logistic regression analysis
      revealed that SOS was an independent factor predicting lower FRL hypertrophy
      after PVE (Delta% FRL <20: hazard ratio 31.7, 95% confidence interval 2.84
      355.12; P = 0.005). The incidence of postoperative transient liver failure after
      the 2nd-stage hepatectomy in patients presenting with SOS was higher than that in
      those without SOS, but the difference did not reach significance (25.0% vs 4.0%;
      P = 0.052). Steatohepatitis was confirmed at the 1st- and 2nd-stage hepatectomy
      in 6 (14.3%) and 3 (6.7%) patients, respectively. CONCLUSION: Sinusoidal
      obstruction syndrome inhibits FRL hypertrophy after PVE and induces postoperative
      liver failure. Therefore, an alternative strategy is needed to perform TSH safely
      in the presence of SOS.

PMID- 21191687
TI  - Human adipose-derived stem cells: potential clinical applications in surgery.
AB  - Regenerative medicine is emerging as a rapidly evolving field of research and
      therapeutics. Stem cells hold great promise for future translational research and
      clinical applications in many fields. Much research has focused on mesenchymal
      stem cells isolated from bone marrow in vitro and in vivo; however, bone marrow
      procurement causes considerable discomfort to the patient and yields a relatively
      small number of harvested cells. By contrast, adipose tissue represents an
      abundant and easily accessible source of adult stem cells, termed adipose-derived
      stem cells (ADSCs), with the ability to equally differentiate along multiple
      lineage pathways. These stem cells have angiogenic properties, possibly because
      of their secretion of cytokines. They may also play a role in healing acute and
      chronic tissue damage. Subsequently, they have a wide range of potential clinical
      implications. This article reviews the potential preclinical and clinical
      applications of mesenchymal stem cells, especially ADSCs, in surgery.

PMID- 21191689
TI  - Laparoscopic hepatectomy: a systematic review, meta-analysis, and power analysis.
AB  - PURPOSE: A previous meta-analysis study demonstrated that bleeding and the
      duration of the hospital stay following laparoscopic hepatectomy (Lap) were
      significantly smaller and shorter, respectively, than for patients undergoing an
      open approach (Op). The aim of the present study was to re-evaluate perioperative
      variables and adverse outcomes in patients undergoing Lap versus (vs) Op after
      2000. METHODS: A PubMed and Ovid Medline search identified clinical studies that
      compared the outcomes of Lap vs Op patients after 2000. A meta-analysis and power
      analysis were performed. RESULTS: Operative time was not significantly different
      between the two approaches (95% confidence interval [CI]: -0.063 to 0.992).
      Patient bleeding in the Lap group was significantly lower than in the Op group
      (95% CI: -1.027 to -0.390). Complications with Lap patients were significantly
      less frequent (95% CI: 0.231-0.642), and the duration of the hospital stay for
      Lap patients was significantly shorter (95% CI: -0.950 to -0.530) than for Op
      patients. Only one paper presented 80% power with 0.05 alpha-errors in all four
      outcomes, whereas four studies did not have sufficient statistical power.
      CONCLUSIONS: The clinical benefits of Lap include a smaller incidence of
      complications and a shorter duration of hospital stay at the current time.
      Several studies had too few cases to sufficiently evaluate these factors,
      although other studies were appropriately analyzed.

PMID- 21191690
TI  - Menstruation recovery after chemotherapy and luteinizing hormone-releasing
      hormone agonist plus tamoxifen therapy for premenopausal patients with breast
      cancer.
AB  - PURPOSE: Little is known about the period required for menstruation recovery
      after long-term luteinizing hormone-releasing hormone (LH-RH) agonist plus
      tamoxifen therapy following chemotherapy. In this study we investigated the
      period required for menstruation recovery after the therapy. METHODS: The
      subjects comprised 105 premenopausal breast cancer patients who had undergone
      surgery. All patients were administered an LH-RH agonist for 24 months and
      tamoxifen for 5 years following the postoperative adjuvant chemotherapy, and the
      status of menstruation recovery was examined. RESULTS: Menstruation resumed in 16
      cases (15.2%) after the last LH-RH agonist treatment session. The mean period
      from the last LH-RH agonist treatment to the recovery of menstruation was 6.9
      months. The rate of menstruation recovery was 35.5% in patients aged 40 years or
      younger and 8.0% in those aged 41 years or older, and it was significantly higher
      in those aged 40 years or younger. The period until menstruation recovery tended
      to be longer in older patients at the end of treatment. CONCLUSION: This study
      showed that menstruation resumed after treatment at higher rates in younger
      patients. However, because it is highly likely that ovarian function will be
      destroyed by the treatment even in young patients, it is considered necessary to
      explain the risk to patients and obtain informed consent before introducing this
      treatment modality.

PMID- 21191688
TI  - Genomic and epigenetic profiles of gastric cancer: potential diagnostic and
      therapeutic applications.
AB  - Knowledge about the molecular profile of tumor tissues is crucial to effectively
      target cancer cells, because cancer is a genetic disease that involves multiple
      genetic and epigenetic alterations. Prominent aberrations include gene mutation,
      amplification, loss or deletion, as well as epigenetic alterations of the
      promoter DNA CpG islands. All of these aberrations can lead to dynamic changes in
      cancer cells, as demonstrated using resected tumor samples. There are two
      distinct pathological types of gastric cancer: the diffuse type and the
      intestinal type of gastric cancer. Diffuse type gastric cancer harbors
      aberrations in the FGFR2/ErbB3/PI3 kinase pathway, while intestinal type gastric
      cancer has an activated ErbB2 oncogenic pathway. On the other hand, the
      prometastatic oncogene PRL-3 is commonly activated in both types of advanced
      gastric cancer, and might represent a relevant therapeutic target for gastric
      cancer with lymph node metastasis or peritoneal dissemination. Numerous tumor
      suppressor genes can inhibit such oncogenic pathways, and DNA methylation in CpG
      islands of gene promoters is frequently found to suppress the expression of such
      genes in gastric cancer. Helicobacter pylori infection in normal gastric mucosa
      may cause p53 mutations through activation of activation-induced cytidine
      deaminase (AID) and/or promoter DNA methylation of E-cadherin, an initiator of
      gastric cancer, and such abnormalities are found even in the precancerous stage
      of gastric carcinogenesis. In addition, it has been demonstrated that there are
      highly relevant methylation genes involved in cancer (HRMGs) that exhibit very
      frequent cancer-specific methylation in gastric cancer. Such genes are potential
      targets for cancer treatment, and might also serve as biomarkers of gastric
      cancer for either the diagnosis or for determining the prognosis or the response
      to treatment.

PMID- 21191691
TI  - Results of a pulmonary metastasectomy in patients with colorectal cancer.
AB  - PURPOSE: The lung is one of the key sites of hematogenous metastasis in patients
      with colorectal cancer. A metastasectomy of the lung is reported to improve the
      prognosis of colorectal cancer. We reviewed our experience in evaluating the
      surgical outcomes in colorectal cancer patients who have undergone a pulmonary
      metastasectomy. METHODS: A single-center retrospective evaluation of clinical
      prognostic factors (1996-2008) related to a pulmonary metastasectomy of patients
      with colorectal cancer was conducted. Fifty-seven consecutive patients in our
      hospital who had undergone a resection of pulmonary metastasis from colorectal
      cancer were retrospectively investigated. RESULTS: The mean age of the patients
      who underwent an initial pulmonary metastasectomy was 63.8 years. The average
      number of pulmonary metastases was 3.8. Pulmonary metastasectomy was performed an
      average of 1.6 times per head. A total of 32 patients had undergone a liver
      metastasectomy, and the 5-year survival of these 32 patients was 43.1%. The 5
      year survival of the time from first pulmonary metastasectomy was 53.9%. There
      were no statistical differences with regard to the disease-free interval,
      interval from primary resection, or the number of pulmonary metastasectomies.
      CONCLUSIONS: A pulmonary resection for colorectal pulmonary metastases is
      therefore considered to be a favorable treatment for long-term survival even in
      the presence of liver metastases. Thoracic surgeons should therefore aggressively
      perform a pulmonary metastasectomy of colorectal cancer.

PMID- 21191692
TI  - The results of surgery under general anesthesia in patients with lung cancer.
AB  - PURPOSE: There are few reports of surgical complications for underweight
      patients. This study evaluated the complications associated with lung cancer
      surgery and anesthesia in underweight patients in a comparison with obese ones.
      METHODS: A single-center retrospective evaluation of perioperative complications
      was conducted in 756 patients who underwent thoracic surgery under general
      anesthesia between 1996 and 2006. The body mass index showed that 39 were
      extremely underweight (<17.2 kg/m(2)), 45 were underweight (17.2-18.4 kg/m(2)),
      513 were normal (18.5-24.9 kg/m(2)), and 159 were obese (>24.9 kg/m(2)). RESULTS:
      Extremely underweight patients had the most preoperative thoracic disease such as
      emphysema, whereas obese patients had the most preoperative cardiovascular
      disease such as hypertension. The postresection-predicted pulmonary function
      showed no difference among the four groups. Extremely underweight patients had an
      increased incidence of intraoperative hypotension and arrhythmia in comparison to
      underweight patients. On the other hand, obese patients had the majority of
      intraoperative thoracic complications such as hypoxia. Extremely underweight
      patients had more postoperative thoracic complications, especially pneumonia and
      pulmonary air leakage, than other patients. CONCLUSIONS: Extremely underweight
      patients as well as obese patients had a high risk of perioperative
      complications, especially postoperative thoracic complications. Extremely
      underweight patients should therefore be carefully observed with regard to
      respiratory management.

PMID- 21191693
TI  - Surgical outcome of simultaneous carotid and cardiac surgery.
AB  - PURPOSE: The surgical outcome of a simultaneous carotid endarterectomy and
      cardiac surgery has not been clarified. This study retrospectively reviewed short
      and mid-term outcomes after a carotid endarterectomy combined with valvular
      surgery or coronary artery bypass grafting (CABG). METHODS: Fifteen patients (12
      males and 3 females, mean age 68.9 +/- 6.7, range 59-86 years) underwent a
      carotid endarterectomy combined with cardiac surgery. The main indication for
      carotid endarterectomy was more than 75% carotid stenosis with or without
      cerebral ischemic symptom. Eight patients had a history of stroke or transient
      ischemic attack. Endarterectomy was performed under mild hypothermia and
      controlled hemodynamics with pulsatile perfusion with cardiopulmonary bypass in
      all cases. Concomitant cardiac procedures were aortic valve replacement in 1
      patient and CABG in 14 patients. RESULTS: There was no early death. Early
      neurological complications occurred in only 1 patient (6.7%). The ratio of heart
      type fatty acid binding protein increased significantly in those that suffered
      postoperative neurological complications. One patient died 6 months after the
      operation due to pneumonia. There was no myocardial infarction, and no events
      were observed in the late postoperative periods. CONCLUSIONS: Carotid
      endarterectomy can be safely performed in combination with cardiac surgery.
      Furthermore, the heat-type fatty acid binding protein levels might be useful for
      predicting early neurological complications.

PMID- 21191694
TI  - Management of open abdomen with an absorbable mesh closure.
AB  - PURPOSE: To examine the methods and results of treatment in patients with an open
      abdomen (OA) at a single institution where an absorbable mesh closure (AMC) is
      most commonly used. METHODS: A retrospective study was performed in OA patients
      from January 2001 to June 2007. Outcomes were analyzed in terms of
      enteroatmospheric fistula (EAF) formation and survival. RESULTS: There were 73 OA
      patients receiving definitive closures (40 trauma and 33 nontrauma). Twenty-four
      patients were able to undergo a delayed primary fascial closure (DPFC) after
      initial vacuum pack closure (DPFC rate 33%). The DPFC rate was significantly
      lower in patients with an associated infection or contamination (9% vs 44%, P =
      0.002). The EAF and mortality rates of the DPFC group were 0% and 13%,
      respectively. Absorbable mesh closure was used in 41 of 49 patients who failed
      DPFC (84%). There were 9 patients who had EAF (overall EAF rate 12%), 6 of whom
      were in the AMC group (EAF rate 15%). The overall and AMC group mortality rates
      were 29% and 37%, respectively. CONCLUSION: Absorbable mesh closure carries high
      EAF and mortality rates. Therefore, DPFC should be considered as the primary
      closure method. Absorbable mesh closure should be reserved for patients who fail
      DPFC, especially those with peritonitis or contamination.

PMID- 21191695
TI  - Factors affecting reversal following Hartmann's procedure: experience from two
      district general hospitals in the UK.
AB  - PURPOSE: Restoration of gastrointestinal continuity following Hartmann's
      procedure is a challenging task associated with significant morbidity and
      mortality. New strategies to avoid a stoma are not readily available in general
      hospitals. Knowledge of the factors related to reversal is required to develop
      treatment strategies and counsel patients realistically. The present study was
      conducted to determine the reversal rate and factors affecting Hartmann's
      reversal in our practice. METHODS: This study retrospectively reviewed the
      medical records of patients who underwent Hartmann's procedure and its reversal
      in two United Kingdom District Hospitals between January 1996 and December 2005.
      RESULTS: Case notes from 184 patients were reviewed. Hartmann's procedure was
      reversed in 51 (34.7%) of the surviving patients, with a complication rate of
      37.3% and no mortality. Reversal of Hartmann's procedure was significantly
      related to patient age (P < 0.001), mode of admission (P = 0.003), American
      Society of Anesthesiologists grading (P = 0.003), Dukes' staging (P = 0.003),
      benign pathology (P = 0.001), and extracolonic cancer (P = 0.023). CONCLUSIONS:
      Despite the challenging nature of Hartmann's reversal, colostomy closure can be
      achieved without mortality in a district general hospital. Familiarity with the
      factors associated with reversal should enable a genuine discussion with patients
      regarding reversal.

PMID- 21191696
TI  - A multicenter phase II clinical study of oxaliplatin, folinic acid, and 5
      fluorouracil combination chemotherapy as second-line treatment for advanced
      colorectal cancer: a Japanese experience.
AB  - PURPOSE: This multicenter phase II study was designed to determine the efficacy
      and tolerability of oxaliplatin, levoforinate, and infusional 5-fluorouracil
      (FOLFOX4) as a second-line therapy for Japanese patients with unresectable
      advanced or metastatic colorectal cancer. METHODS: A total of 53 patients with
      progressive disease after first-line chemotherapy were enrolled in the study. The
      treatment was repeated every 2 weeks until disease progression or unacceptable
      toxicity occurred, or the patient chose to discontinue the treatment. RESULTS:
      Four patients were ineligible and one did not receive the protocol therapy.
      Therefore, the response rate, overall survival (OS), and progression-free
      survival (PFS) were evaluated in 48 patients; toxicity was evaluated in 52
      patients, excluding the patient who had not received the protocol therapy. A
      partial response was observed in 10 patients. The overall response rate was 20.8%
      (95% confidence interval [CI], 10.5%-35.0%). The median PFS was 5.6 months (95%
      CI, 4.1-7.0 months) and the median OS was 19.6 months (95% CI, 11.4-24.3 months).
      The most frequently encountered grade 3/4 hematological symptom was neutropenia
      (43.1%). The toxicity profile was generally predictable and manageable.
      CONCLUSION: The results showed good tolerability and efficacy for second-line
      FOLFOX4 in patients with advanced colorectal cancer, thus indicating the promise
      of this regimen as an effective second-line therapy for advanced colorectal
      cancer in the Japanese population.

PMID- 21191697
TI  - Solid pseudopapillary tumor of the pancreas: the surgical procedures.
AB  - PURPOSE: To evaluate the clinicopathological characteristics of solid
      pseudopapillary tumor and assess the curative effects of different procedures.
      METHODS: A retrospective review was performed in 34 patients with this tumor
      surgically treated between January 2000 and June 2008. These patients were
      divided into minimized and standard resection groups. The clinical data of the
      two groups were analyzed. RESULTS: Thirty-one females and three males were
      included in this study. There were no significant differences in age, blood
      glucose, hemoglobin, and albumin between the two groups. The surgical time for
      patients with a standard resection was longer (225 vs 124 min, P = 0.004), the
      transfusion rate was higher (52.6% vs 13.3%, P = 0.030), and the hospital stay
      was prolonged (21 vs 16 days, P = 0.034) in comparison to those who underwent a
      minimized resection. The complications rate in the standard resection group was
      higher than that in the minimized resection group, although no significant
      difference was found (42.1% vs 26.7%, P = 0.476). The long-term follow-up showed
      that all of the patients survived without recurrence except for one patient who
      died of other diseases 29 months after surgery. CONCLUSION: A solid
      pseudopapillary tumor is a latent malignant tumor with excellent prognosis after
      its complete removal. When feasible, a minimized resection, such as enucleation
      and a segmental pancreatectomy, is a suitable approach, with excellent early and
      long-term results.

PMID- 21191698
TI  - Is modified Devine exclusion necessary for gastrojejunostomy in patients with
      unresectable pancreatobiliary cancer?
AB  - PURPOSE: Gastrojejunostomy is often performed as palliative surgery for
      unresectable pancreatobiliary cancer. Modified Devine exclusion (MDE) is a
      technical variation of gastrojejunostomy, which partially separates the mid
      portion of the stomach. We conducted this study to assess whether MDE is
      necessary for gastrojejunostomy in patients with unresectable pancreatobiliary
      cancer. METHODS: We compared the postoperative results of MDE (n = 26) with those
      of conventional gastrojejunostomy (CGJ; n = 20) performed palliatively for
      unresectable pancreatobiliary cancers. RESULTS: The morbidity rates were 38%
      after MDE and 50% after CGJ, with 23% and 40% of patients suffering delayed
      gastric emptying, respectively. Two of the CGJ group patients could never eat
      again. Modified Devine exclusion slowed the progression of anemia in all of the
      patients with duodenal bleeding. CONCLUSION: Modified Devine exclusion may be
      effective for patients with unresectable pancreatobiliary cancer.

PMID- 21191699
TI  - Surgical impacts of an en bloc resection of the diaphragm for hepatocellular
      carcinoma with gross diaphragmatic involvement.
AB  - PURPOSE: Diaphragmatic involvement is relatively uncommon in patients undergoing
      a hepatectomy for hepatocellular carcinoma (HCC). The aim of this study was to
      evaluate the short- and long-term surgical impacts of HCC with gross
      diaphragmatic involvement in patients undergoing an en bloc resection of the
      diaphragm. METHODS: Between 1990 and 2007, 911 patients with HCC underwent a
      hepatectomy at our institution. Twenty-seven patients (3.0%) had had gross
      involvement of the diaphragm. Thirteen patients (1.4%) had undergone an en bloc
      resection of the diaphragm, and 14 (1.5%) had received only a blunt dissection.
      The short-term surgical impacts (surgical morbidity and mortality) and long-term
      surgical impacts (overall and disease-free survival) were compared between the
      groups. RESULTS: In patients with an en bloc resection of the diaphragm as
      compared with those who received a blunt dissection, the values of total
      bilirubin and the indocyanine green retention rate at 15 min were significantly
      better (P < 0.01 and P = 0.04, respectively), and the rate of positivity for the
      hepatitis B antigen was significantly higher (P = 0.02). The positive rates of
      microscopic fibrocapsular invasion (P = 0.03), microscopic vascular invasion (P =
      0.04), and Ki-67 immunostaining (P = 0.04) were significantly higher in patients
      with an en bloc resection of the diaphragm. There were no significant differences
      in the short-term and long-term surgical impacts between the groups. CONCLUSION:
      An en bloc resection of the diaphragm in patients with gross diaphragmatic
      involvement of HCC is therefore justified, since there are no significant
      differences in short- or long-term surgical impacts in comparison with the
      patients receiving blunt dissection.

PMID- 21191700
TI  - LKB1 gene alterations in surgically resectable adenocarcinoma of the lung.
AB  - PURPOSE: Germline mutations of LKB1 (also known as SKT11; locus 19p13.3) cause
      the occurrence of autosomal dominant Peutz-Jeghers syndrome (PJS). Nearly half of
      the non-small cell lung cancer (NSCLC) cell lines and one-third of lung
      adenocarcinoma in Caucasian patients have an LKB1 mutation. METHODS: This study
      examined the mutational hot spots of the LKB1 gene in surgical resectable lung
      adenocarcinoma. Exons 1, 6, and 7 of the LKB1 gene were sequenced in 174 Japanese
      patients with lung adenocarcinoma (including 157 men and 17 women). RESULTS: Only
      five patients had LKB1 gene alterations (2.9%). All of them were male smokers,
      and no LKB1 mutation was observed in any of the females. The details of LKB1
      alterations were: one 5 bp deletion in intron 5, one Gly to Phe substitution at
      codon 279 of exon 6, and three Pro to Leu substitutions at codon 281 of exon 6.
      The P281L alteration and 5 bp deletion in the intron 5 were found to be germline
      polymorphisms. The G279F was confirmed to be a novel somatic mutation. None of
      the five patients with an LKB1 alteration showed either an EGFR or K-ras
      mutation. CONCLUSION: The LKB1 gene alteration is rare in Japanese patients with
      lung adenocarcinoma, and is generally limited to male smokers.

PMID- 21191701
TI  - Changes in the pleural cavity by pleurodesis using talc or OK-432: an
      experimental study.
AB  - PURPOSE: To define the changes in the pleural cavity after pleurodesis induced by
      talc or OK-432. METHODS: A total of 30 rats were divided into three groups: a
      normal saline group (control group, n = 10), a group administered 400 mg/kg talc
      (talc group, n = 10), and a group administered 0.3 KE/kg OK-432 (OK-432 group, n
      = 10). Pleural cavities were examined and scored on the 30th day after the
      intrapleural administration of each agent. RESULTS: Both the talc group and OK
      432 group showed significantly higher macroscopic or microscopic pleurodesis
      scores than the control group (P < 0.05). Upon microscopic evaluation, the
      pleurodesis scores in the talc group were significantly higher than those in the
      OK-432 group (P < 0.01).The majority of the pleural thickness was found on the
      visceral pleura, and the parietal pleura was very thin. The thickness of the
      visceral pleura in the talc group was significantly higher than that in the OK
      432 group (P < 0.005). Pathologically, the pleural thickening in the talc group
      consisted of fibrous tissue with injury of the pleural mesothelium, and talc
      particles were seen in the submesothelial fibrotic tissue and inside the alveoli.
      CONCLUSIONS: Talc pleurodesis induces more marked changes in the pleural cavity
      than OK-432-induced pleurodesis.

PMID- 21191702
TI  - Successful treatment of a visceral artery aneurysm with a celiacomesenteric
      trunk: report of a case.
AB  - A celiacomesenteric trunk is an anomaly in which the celiac and superior
      mesenteric arteries have a common origin from the aorta. This structure accounts
      for less than 1% of all visceral artery anomalies, and is estimated to have an
      incidence of 0.25%. Aneurysms involving a celiacomesenteric trunk are
      exceptionally rare. We herein report our treatment modality for an 82-year-old
      man with a visceral artery aneurysm involving a celiacomesenteric trunk. The
      aneurysm was resected, and the superior mesenteric, splenic, and common hepatic
      arteries were successfully reconstructed.

PMID- 21191703
TI  - Giant fibrovascular polyp of the esophagus: report of a case.
AB  - A fibrovascular polyp is a peculiar nonepithelial tumor of the esophagus that
      invariably arises in the cervical esophagus at the level of the thoracic inlet
      and grows distally into a massive elongated, pedunculated, intraluminal lesion.
      Although it is a benign lesion that is eminently resectable, it is a dramatic
      entity owing to its tendency to cause bizarre complications such as asphyxia and
      sudden death when it regurgitates into the pharynx and causes laryngeal
      impaction. This report describes the multimodality imaging appearance of an
      archetypal case of a giant fibrovascular polyp in a patient with a seemingly
      innocuous presentation for the size of the lesion. The essential role of cross
      sectional imaging in establishing a prompt diagnosis, defining the tissue
      elements of the mass, and delineation of the exact extent of the lesion in
      guiding the treatment approach is highlighted. The appearance of fibrovascular
      polyp in a single patient with a combination of barium swallow, multidetector
      computed tomography, and high-resolution contrast-enhanced magnetic resonance
      imaging has not been reported previously.

PMID- 21191704
TI  - Gastric carcinoma with protein-losing gastroenteropathy: report of a case.
AB  - This report describes the successful treatment of a case of true gastric cancer
      presenting as protein-losing gastroenteropathy. A 58-year-old Japanese male
      presented gastric carcinoma. His serum albumin and total protein levels were 1.8
      and 4.2 g/dl, respectively. He was diagnosed with gastric cancer with protein
      losing gastroenteropathy based on (99m)Tc-human serum albumin scintigraphy. The
      patient underwent a total gastrectomy following neoadjuvant chemotherapy. There
      are 23 detailed case reports of gastric carcinoma with protein-losing
      gastroenteropathy. Most of these cases had large villous or cauliflower-like
      gastric tumors that were defined as papillary or well differentiated
      adenocarcinoma. Gastric cancer with protein-losing gastroenteropathy is extremely
      rare, but it can easily be diagnosed if the villous or cauliflower-like features
      are well defined.

PMID- 21191705
TI  - Type IV jejunal atresia with an unusual variation of enteric duplication: report
      of a case.
AB  - We report a rare case of type IV jejunal atresia with enteric duplication and
      multiple diverticuli, found in a 3-day-old baby girl. To our knowledge, this
      association has never been reported before.

PMID- 21191706
TI  - Single-incision laparoscopic gastric resection for submucosal tumors: report of
      three cases.
AB  - Between March and April 2009, three consecutive patients underwent single
      incision laparoscopic gastric wedge resection for a submucosal tumor located in
      the anterior wall or greater curvature of the stomach. First, we placed two or
      three trocars through the same infra-umbilical skin incision. Then, we either
      elevated the tumor with a mini-loop retractor or retracted the gastric wall near
      the tumor with a laparoscopic grasper. Finally, we resected the tumor using an
      endoscopic linear stapler. Single-incision laparoscopic gastric resection was
      successfully completed in all three patients without the need for any
      extraumbilical skin incisions or conversion to conventional laparoscopic
      procedures. There was no morbidity. The mean operating time and blood loss were
      86 min and 4 ml, respectively, and the mean tumor size and surgical margin were
      34 mm and 8 mm, respectively. Histopathologically, two tumors were diagnosed as
      gastrointestinal stromal tumors and one as a carcinoid tumor. Thus, single
      incision laparoscopic gastric resection for submucosal tumors is safe and
      feasible when performed by experienced laparoscopic surgeons using conventional
      laparoscopic instruments.

PMID- 21191707
TI  - Early postoperative heterotopic omental ossification: report of a case.
AB  - Heterotopic mesenteric ossification (HMO) is an uncommon disorder that may
      sometimes be misdiagnosed. It can cause bowel or intestinal perforation, which
      may also lead to serious complications or even death. Heterotopic bone formation
      in the omentum, which is called heterotopic omental ossification (HOO) and is one
      type of HMO, is considered to be an exceedingly rare event. To our knowledge,
      about 29 cases of HMO have been reported in previous studies, of which three were
      HOO. We herein describe a case of HOO occurring in a 39-year-old Chinese man with
      no medical history of abdominal surgery. He underwent a left hemicolectomy, which
      was performed for the treatment of descending colon adenocarcinoma. Two weeks
      later, he developed a small bowel obstruction associated with multiple foci of
      heterotopic bone formation within the omentum. He therefore underwent a second
      surgical procedure for adhesiolysis and a partial omentectomy. The postoperative
      course was uneventful. He is still alive and disease-free 16 months later.

PMID- 21191708
TI  - Cystic peritoneal mesothelioma: report of a case.
AB  - Benign multicystic peritoneal mesothelioma (BMPM) is a rare disease with good
      short-term prognosis and rare malignant transformation. However, its biological
      significance remains unexplained. A neoplastic origin is considered by many
      authors to require a surgical excision, based on the high recurrence and
      progressive growth rate of the tumors. However, alternative or integrative
      treatment options have also been proposed. A 45-year-old woman presented to our
      unit with a history of occasional discomfort and pain in the left hip. On
      physical examination, we noticed a tough-elastic, fixed mass located in the iliac
      fossa. Computed tomography scan detected a mass with multiseptated cystic-like
      areas. Due to the similarity of these findings to a primitive sarcomatous tumor
      of the retroperitoneum, an arteriographic study was also performed. The patient
      underwent en bloc resection of the mass, including a segment of the sigmoid
      colon. The final pathologic diagnosis was cystic mesothelioma. Further studies
      are needed to better understand the etiology and pathogenesis of this rare
      disease, and to define a more tailored treatment plan.

PMID- 21191709
TI  - Noninvasive intraductal papillary mucinous neoplasm with para-aortic lymph node
      metastasis: report of a case.
AB  - Intraductal papillary mucinous neoplasms (IPMNs) with an invasive carcinoma
      component are categorized as minimally invasive or invasive. The prognosis after
      resection of minimally invasive IPMNs has been reported to be similar to that
      after resection of noninvasive IPMNs. We report a case of noninvasive branchduct
      IPMN with multiple lymph node metastases, including para-aortic node involvement,
      treated successfully by distal pancreatectomy with lymph node dissection. The
      patient, a 72-year-old man, had two multilocular cysts in the pancreatic body, 22
      mm and 14 mm in diameter, respectively, communicating with the main pancreatic
      duct. The primary tumor and nodal metastases had similar patterns of mucin
      expression. The primary tumor contained a region of carcinoma in situ (CIS)
      without histological evidence of stromal invasion; thus, it was diagnosed as
      minimally invasive carcinoma. We report this case to emphasize two important
      points: first, even small branch-duct IPMNs without any indications for resection
      can have a component of CIS or more advanced disease; and second, even branch
      duct IPMNs without any apparent invasive component can be aggressive and spread
      to the lymph nodes. Therefore, nodal status should be assessed carefully in every
      patient, even if the primary IPMN is not advanced.

PMID- 21191710
TI  - Giant hemorrhagic adrenal pseudocyst in a primiparous pregnancy: report of a
      case.
AB  - Adrenal cysts are rare and are usually discovered incidentally during diagnostic
      imaging, surgery, or autopsy. Most cystic lesions of the adrenal gland are
      nonfunctioning and become symptomatic when complicated by rupture, hemorrhage, or
      infection. A 40-year-old woman presented with a history of gradual-onset pain in
      her left flank region at 20 weeks' gestation. Ultrasound showed a 20-cm cystic
      mass in her left abdominal cavity. Pertinent laboratory tests were within normal
      limits. The patient underwent exploratory laparotomy, which revealed a 20 * 15-cm
      left adrenal cyst; thus, we performed left adrenalectomy with complete excision
      of the cyst. Histological examination confirmed a hemorrhagic adrenal pseudocyst.
      The patient had an uneventful postoperative course, and subsequent routine
      obstetric ultrasound examinations showed normal fetal activity and development
      until the pregnancy terminated with a stillbirth caused by pre-eclampsia at 34
      weeks' gestation. To the best of our knowledge, this is only the 12th reported
      case of adrenal pseudocyst discovered during pregnancy. We analyze the
      clinicopathologic findings and discuss the possible association of pregnancy,
      with special reference to etiopathogenesis, presentation, diagnosis, and
      treatment.

PMID- 21191711
TI  - Treatment of age-related macular degeneration: beyond VEGF.
AB  - Current therapy for age-related macular degeneration (AMD) shows a dramatic
      change from clinical practice a decade ago. While the first pharmacologic
      treatment, verteporfin photodynamic therapy (PDT) slowed disease progression,
      newer anti-vascular epithelial growth factor (VEGF) therapies have also shown
      vision improvement in many patients. Combination therapies (PDT + steroid + anti
      VEGF) have shown some promise, particularly in certain classes of disease.
      Genetic studies have identified common gene variants in the complement factor H
      gene that confers susceptibility to AMD, and treatments targeting the complement
      pathway are being explored. Another area of research is directed at the
      components of Bruch membrane; studies of changes in the elastic fibers and
      collagen within Bruch may yield drug targets for prevention and halting of
      disease progression. Finally, studies in photoreceptor apoptosis have identified
      the role of cytokines, such as monocyte chemotactic protein 1, tumor necrosis
      factor alpha, and interleukin 1beta, associated with photoreceptor cell death and
      should be pursued as potential therapies to improve vision outcomes in
      neovascular AMD. Today's research into the biology of AMD will lead us to better
      treatment and perhaps even preventive measures in the decades ahead.

PMID- 21191712
TI  - Validation of international criteria for the diagnosis of ocular sarcoidosis
      proposed by the first international workshop on ocular sarcoidosis.
AB  - PURPOSE: To validate the international criteria for the diagnosis of ocular
      sarcoidosis as proposed by the First International Workshop on Ocular Sarcoidosis
      (FIWOS). METHODS: A retrospective case-control study examined 370 consecutive
      uveitis patients at Tokyo Medical and Dental University Hospital. The study group
      consisted of 50 patients with biopsy-proven sarcoidosis and 320 control patients
      with other uveitis entities. Predictive values [sensitivity, specificity,
      positive predictive value (PPV), and negative predictive value (NPV)] were
      calculated for seven clinical signs, five laboratory tests, and the diagnostic
      criteria. RESULTS: With the exception of the liver enzyme tests, there was a
      significantly higher incidence of positive results for all clinical signs and
      laboratory tests in the biopsy-proven sarcoidosis patients than in the control
      uveitis patients. Although variability was noted in the predictive values of the
      seven clinical signs and five laboratory tests, the sensitivity, specificity,
      PPV, and NPV of the FIWOS criteria, which were based on the combined results of
      the clinical signs and laboratory tests, were 1.000, 0.956, 0.781, and 1.000,
      respectively. CONCLUSIONS: The FIWOS criteria have high predictive values for
      diagnosing ocular sarcoidosis. To further confirm these findings, an
      international prospective multicenter study should be undertaken in the future.

PMID- 21191713
TI  - Simultaneous deep anterior lamellar keratoplasty and limbal allograft in
      bilateral limbal stem cell deficiency.
AB  - PURPOSE: To report the efficacy of simultaneous keratolimbal allograft (KLAL)
      surgery and deep anterior lamellar keratoplasty (DALK) for limbal stem cell
      deficiency (LSCD). METHODS: We conducted a retrospective, interventional case
      series of six consecutive eyes of five patients with LSCD and stromal opacity due
      to gelatinous drop-like dystrophy (two eyes), Stevens-Johnson syndrome (SJS, two
      eyes), or aniridia (two eyes). Only patients with normal lid anatomy and Schirmer
      test values greater than 3 mm were enrolled. DALK was performed by
      viscodissection followed by a thin, 360 degrees  KLAL designed by using an
      artificial anterior chamber. KLAL sutures were removed after 2 weeks. RESULTS:
      DALK and KLAL were successfully performed in all eyes, which were followed for an
      average of 17.2 +/- 10.8 months. All eyes recovered a smooth corneal epithelium,
      although one SJS patient developed a persistent epithelial defect (PED) leading
      to opacification of the central cornea. Visual acuity improved by more than 2
      lines in all eyes except that of the SJS patient with PED. No other complications
      were observed. CONCLUSION: Simultaneous DALK and thin-section KLAL is an
      effective treatment for ocular surface disease in patients with residual tear
      function and normal lid anatomy.

PMID- 21191714
TI  - Spectral-domain optical coherence tomography and scanning laser polarimetry in
      glaucoma diagnosis.
AB  - PURPOSE: To evaluate glaucoma diagnostic capability of the retinal nerve fiber
      layer (RNFL) imaging by spectral-domain optical coherence tomography (Cirrus OCT)
      and scanning laser polarimetry (GDx VCC). METHODS: We imaged 88 glaucomatous and
      77 healthy eyes using both devices. Areas under the receiver-operating
      characteristic curves (area under the curves, AUCs) and sensitivities at fixed
      specificities of average, superior, and inferior RNFL thickness were compared.
      Likelihood ratios (LRs) and diagnostic agreement based on normative
      classifications yielded by both devices were determined. RESULTS: The best
      performing parameter was the nerve fiber indicator (NFI) in GDx VCC and inferior
      RNFL thickness in Cirrus OCT (AUC = 0.912, 0.961, P = 0.045). The AUCs of the
      Cirrus OCT were significantly higher than those of GDx VCC in all parameters.
      Most of the parameters in Cirrus OCT were more sensitive than GDx VCC in the
      detection of glaucoma at fixed specificity values. Cirrus OCT had an infinite LR
      with abnormal classification results in both average and superior RNFL thickness.
      There was good agreement between the two instruments with respect to abnormal
      classifications (kappa, 0.611-0.766) CONCLUSION: Both Cirrus OCT and GDx VCC RNFL
      measurements showed good glaucoma diagnostic capabilities. Cirrus OCT showed
      higher sensitivities than GDx VCC.

PMID- 21191715
TI  - Molecular genetic investigations of contaminated contact lens storage cases as
      reservoirs of Pseudomonas aeruginosa keratitis.
AB  - PURPOSE: To elucidate the reservoirs of Pseudomonas aeruginosa keratitis
      associated with contact lens (CL) wear by using a molecular genotyping method.
      METHOD: Ten P. aeruginosa isolates obtained from two young adult patients with
      infectious keratitis associated with CL wear were studied. These were isolated
      from corneal specimens, conjunctival swabs, discharges, CL storage cases, and the
      living environment of the two patients. Species identification was performed with
      an Oxi/Ferm Tube II system using well-separated colonies on MacConkey and NAC
      agar plates. We employed molecular genotyping by pulsed-field gel
      electrophoresis. RESULTS: We isolated three (one each from a corneal scraping,
      discharge, and a CL storage case) P. aeruginosa samples from patient 1, and seven
      (one each from the conjunctival swab, CL storage case, and the patient's fingers,
      and four from the patient's room) from patient 2. Pseudomonas aeruginosa of
      environmental origin could not be obtained from the house of patient 1. The
      genotypes of two P. aeruginosa isolates, from corneal scraping and discharge,
      were identical to that of the isolate from the CL storage case belonging to
      patient 1. In patient 2, the isolates from the eye and the CL storage case showed
      the identical genotype, which was different from those of the environmental
      isolates. CONCLUSION: Our results suggest that the causative P. aeruginosa
      strains in cases of infectious keratitis associated with CL wear originate in
      contaminated CL storage cases. However, it is still unclear whether the
      environmental strains in the patients' houses also cause keratitis.

PMID- 21191716
TI  - Visual acuity following intravitreal bevacizumab for macular edema associated
      with retinal vein occlusion.
AB  - PURPOSE: To study prognostic factors for visual acuity (VA) after intravitreal
      bevacizumab injection (IVB) for macular edema (ME) associated with retinal vein
      occlusion (RVO), by evaluating the correlation between the final VA and VA at
      baseline and at 1, 3, and 6 months after the initial IVB. METHODS: We studied
      retrospectively 79 eyes of 79 patients with ME secondary to RVO treated with IVB.
      The correlation between the final VA and VA at each visit was studied by using
      Pearson's correlation coefficient. RESULTS: Baseline VA was significantly
      correlated with the final VA (r = 0.552, P < 0.0001). Postoperative VA at 1, 3,
      and 6 months after the initial IVB, however, was even more closely correlated
      with the final VA (r = 0.793, 0.816, 0.893, respectively; P < 0.0001 in each
      case). Additionally, eyes with a VA of 20/40 or better at 1 month achieved a
      significantly better final VA than did eyes with a VA worse than 20/40 at 1 month
      (P < 0.0001). This tendency was seen also in each RVO subgroup. CONCLUSION:
      Although the baseline VA was significantly correlated with the final VA,
      postoperative VA was correlated even more closely with the final VA. VA shortly
      after the initial IVB seemed to reliably predict final visual outcome.

PMID- 21191717
TI  - Intravitreal bevacizumab for age-related macular degeneration with good visual
      acuity.
AB  - PURPOSE: To retrospectively study the efficacy of intravitreal bevacizumab (IVB)
      for exudative age-related macular degeneration (AMD) in patients with good visual
      acuity (VA). METHODS: Fifteen eyes of 15 patients (mean age, 69.0 +/- 11.3 years)
      with AMD whose VA was 0.6 or better were treated with IVB 1.25 mg/0.05 ml. The
      patients were followed for 12 to 29 months (mean, 17.4 +/- 4.9 months). RESULTS:
      Best-corrected visual acuity (BCVA) ranged from 0.6 to 1.2 (mean, 0.89 +/- 0.21)
      at baseline and was stable in 13 of 15 eyes (86.7%) when BCVA was 0.6 or better
      at the end of follow-up. The VA levels did not differ significantly (P = 0.42;
      paired t test) between baseline and the final examination. Two of the 15 eyes
      underwent photodynamic therapy during follow-up. The mean central retinal
      thickness significantly decreased from 278.4 +/- 71.9 MUm at baseline to 240.00
      +/- 58.5 MUm at 3 months after the first IVB treatment (P = 0.02; Wilcoxon signed
      rank test). During follow-up, a mean of two injections was administered, and 47%
      of patients required only one injection. No adverse events developed. CONCLUSION:
      IVB was effective for maintaining good vision in exudative AMD in 15 eyes for at
      least 12 months.

PMID- 21191718
TI  - Predictors of response after intravitreal bevacizumab injection for neovascular
      age-related macular degeneration.
AB  - PURPOSE: To identify fluorescein angiography (FA) and optical coherence
      tomography (OCT) characteristics predicting responses to intravitreal bevacizumab
      therapy in patients with neovascular age-related macular degeneration (AMD).
      METHODS: Results of 113 consecutive patients (113 eyes) treated with intravitreal
      bevacizumab injections for neovascular AMD were retrospectively reviewed.
      Patients were categorized into two groups according to visual acuity (VA)
      improvement 1 year after treatment: responders and nonresponders. Responders were
      defined as patients who achieved VA improvement >=7 Early Treatment Diabetic
      Retinopathy Study (ETDRS) letters for occult choroidal neovascularization (CNV),
      and >=11 ETDRS letters for classic CNV at month 12. N onresponders were defined
      as patients who did not meet the above VA improvement at month 12. RESULTS: Of
      the 113 eyes, 36 (31.9%) were categorized as responders and 77 (68.1%) as
      nonresponders. Nonresponders, compared with responders, had thicker subretinal
      tissue (SRT) (218.9 MUm versus 180.9 MUm, P = 0.040), and more frequent cystoid
      macular edema (CME) (42.9% versus 13.9%, P < 0.001). CONCLUSION: Thick SRT and
      CME on OCT may be characteristic of nonresponders and may be helpful for
      tailoring treatment for neovascular AMD.

PMID- 21191719
TI  - Retinal thickness and perimetric sensitivity in central serous chorioretinopathy.
AB  - PURPOSE: To investigate the relationship between anatomical changes and visual
      sensitivity in eyes with central serous chorioretinopathy (CSC). METHODS: Twenty
      one eyes with CSC were retrospectively studied using optical coherence tomography
      (OCT) retinal maps, line scan mode, and the Humphrey perimetry central 10-2
      program. RESULTS: Total retinal thickness (TRT), including the neurosensory
      retina and subretinal fluid, correlated significantly with the sensitivity loss
      in the corresponding visual field in the central macula within a circle 6 mm in
      diameter. Differential analysis of the TRT, separating it into neurosensory
      retinal thickness (NRT) and subretinal thickness (SRT), revealed that only SRT
      correlated well with perimetric sensitivity at 1 degrees , 3 degrees , 5 degrees
      , 7 degrees , and 9 degrees  from the fovea along horizontal and vertical lines
      crossing at the fovea. CONCLUSIONS: Visual sensitivity measured with automated
      static perimetry is further attenuated by increasing distance between the
      photoreceptor and retinal pigment epithelium (RPE) in areas of serous retinal
      detachment in eyes with CSC.

PMID- 21191720
TI  - Difference in redox status of serum and aqueous humor in senile cataract patients
      as monitored via the albumin thiol-redox state.
AB  - PURPOSE: To clarify the redox states of the aqueous humor and serum in senile
      cataract patients. METHODS: We analyzed the reduced and oxidized albumin
      fractions in 58 patients. The patients had no detectable evidence of other eye or
      systemic diseases and were divided into two age groups (53-75 and 76-96 years).
      Analysis was performed with a high-performance liquid chromatographic system with
      a fluorescence detector. RESULTS: Extremely small amounts of reduced albumin
      (3.8% and 3.6% in the younger and older groups, respectively) and markedly large
      amounts of oxidized albumin (96.2% and 96.4%, respectively) were found in the
      aqueous humor. Moreover, a higher percentage of oxidized albumin, particularly a
      highly oxidized irreversible form of albumin, was found in the aqueous humor
      (12.3% and 12.0%) than in the serum (2.4% and 3.0%). CONCLUSIONS: In senile
      cataract patients with no complications, the redox state of albumin in the
      aqueous humor differs considerably, both quantitatively and qualitatively, from
      that in the serum.

PMID- 21191721
TI  - Development of anisometropia in patients after surgery for esotropia.
AB  - PURPOSE: Anisometropia is reported to increase with age; however, the
      relationship between the development of anisometropia and binocular vision has
      not been determined. The purpose of this study was to determine the relationship
      between anisometropia and binocular vision after esotropia (ET) surgery. METHODS:
      The medical records of 51 consecutive patients with ET who had undergone ET
      surgery were studied. Patients with amblyopia or anisometropia >=2 diopters (D)
      before surgery were excluded. The average age of the patients at the time of
      surgery was 4.5 +/- 3.7 years, and the average postoperative period was 5.0 +/-
      2.2 years. The refractive errors (spherical equivalent) in both eyes were
      measured preoperatively and postoperatively. Binocular visual function was
      evaluated with a modified Worth-4 dot test. RESULTS: At the final visit, average
      anisometropia was 0.98 +/- 1.30 D, which was significantly greater than the
      preoperative value of 0.36 +/- 0.46 D (P < 0.001). Anisometropia >=2 D was
      observed in ten patients (23%) postoperatively. One patient was able to fuse a
      target of >=2 degrees  (10%) in the anisometropia >=2 D group, significantly
      fewer than the 13 patients (32%) in the anisometropia <2.0 D group (P = 0.02).
      CONCLUSIONS: Anisometropia may develop in patients with poor sensory fusion after
      surgery for esotropia.

PMID- 21191722
TI  - Calcium channel blocker nilvadipine, but not diltiazem, inhibits ocular
      inflammation in endotoxin-induced uveitis.
AB  - PURPOSE: Calcium channel blockers (CCBs), widely used for hypertensive patients,
      have recently been shown to inhibit atherosclerosis by their antioxidative
      action. The aim of the present study was to examine whether the CCBs nilvadipine
      and diltiazem reduce ocular inflammation in endotoxin-induced uveitis (EIU).
      METHODS: EIU was induced in male C57/B6 mice with a single intraperitoneal
      injection of lipopolysaccharide (LPS). The animals received intraperitoneal
      injections of either nilvadipine, diltiazem, or vehicle for 5 days before the LPS
      application. Twenty-four hours after EIU induction, adherent leukocytes to the
      retinal vasculature were counted with a concanavalin A lectin perfusion-labeling
      technique. The protein concentration in the aqueous humor was measured to assess
      blood-ocular barrier breakdown. Retinal levels of intercellular adhesion molecule
      (ICAM)-1 and monocyte chemotactic protein (MCP)-1 were analyzed by enzyme-linked
      immunosorbent assay. LPS-stimulated generation of superoxide in murine
      microvascular endothelial cells was examined with a nitroblue tetrazolium assay.
      RESULTS: Compared to vehicle treatment, application of nilvadipine, but not
      diltiazem, led to significant suppression of EIU-associated retinal leukocyte
      adhesion, together with anterior-chamber protein leakage, retinal expression of
      ICAM-1 and MCP-1, and LPS-induced superoxide generation in vitro. CONCLUSIONS:
      The CCB nilvadipine exercises an inhibitory effect on the pathogenesis of ocular
      inflammation through the suppression of inflammation-related molecules.

PMID- 21191723
TI  - The effect of C3F8 gas on corneal endothelial cells in rabbits.
AB  - PURPOSE: To evaluate the ocular effects of perfluoropropane gas (C(3)F(8)) in the
      anterior chamber of rabbit eyes in relation to the gas concentration. METHODS:
      Twenty rabbit eyes were randomly divided into four groups (20%, 15%, and 10%
      C(3)F(8) gas groups, and an air control group). After injection of 0.3 ml of each
      gas concentration into the anterior chamber, endothelial damage was evaluated by
      specular microscopic analysis. The main outcome measurements were endothelial
      cell density, hexagonality, coefficient of variation, corneal thickness, and
      intraocular pressure (IOP) 1 day, 1 week, and 2 weeks after injection. Two weeks
      after injection, transmission electronic microscopy was performed to evaluate the
      structural integrity. RESULTS: The 20% group had a significant decrease in
      endothelial cell density (P = 0.023), hexagonality (P = 0.031), and increase in
      corneal thickness (P = 0.045) from baseline to 2 weeks after injection, whereas
      the other groups exhibited no significant differences. The 20% group had a
      significant increase in IOP 1 week after injection (P = 0.041). Transmission
      electron microscopy revealed that the 20% group had a severe flat cell
      configuration with a damaged intracellular organization. CONCLUSIONS: The risk of
      endothelial cell damage and elevation in IOP was greater in the 20% C(3)F(8)
      group than in the 15% or 10% C(3)F(8) groups. Therefore, an appropriate
      concentration of C(3)F(8) gas is needed for different surgical purposes.

PMID- 21191725
TI  - Effects of timolol-related ophthalmic solutions on cultured human conjunctival
      cells.
AB  - PURPOSE: To investigate the inhibitory effects of drugs containing timolol on the
      proliferation of human conjunctival cells in vitro. METHODS: Timoptol, Timoptol
      XE, Rysmon TG, and Timabak solutions were used. These commercially available
      drugs were diluted to 1/30, 1/100, and 1/300, and their effects on cell
      morphology, cell count, and cell activity were investigated. The effects of drugs
      containing benzalkonium chloride (BAK) as well as those of the Rysmon TG vehicle
      alone were also assessed. RESULTS: At 1/30 dilution, cells treated with Timoptol
      and Timoptol XE showed cell deformation. Timoptol and Timoptol XE also caused a
      significant decrease in the number of cells at 1/100 and 1/30 dilutions. Cell
      activity decreased in a concentration-dependent manner after the addition of
      either Timoptol or Timoptol XE. Rysmon TG and Timabak showed significantly higher
      cell activity than Timoptol or Timoptol XE at both 1/100 and 1/30 dilutions. The
      cell count increased in a concentration-dependent manner in the BAK-free group,
      while cell activity decreased in a concentration-dependent manner in the cultures
      in the BAK-containing group. CONCLUSIONS: Compared with Timoptol and Timoptol XE,
      Rysmon TG and Timabak showed milder toxicity on human conjunctival cells in
      vitro.

PMID- 21191724
TI  - Haplotype analysis of the ARMS2/HTRA1 region in Japanese patients with typical
      neovascular age-related macular degeneration or polypoidal choroidal
      vasculopathy.
AB  - PURPOSE: To compare the genomic contribution of the ARMS2/HTRA1 region of
      chromosome 10q26 to typical neovascular age-related macular degeneration (nAMD)
      (also known as typical exudative AMD) and to polypoidal choroidal vasculopathy
      (PCV) METHODS: DNA samples were prepared from 84 patients with typical nAMD, 181
      patients with PCV, and 276 control participants. All of the 18 haplotype-tagging
      single-nucleotide polymorphisms (SNPs) derived from the HapMap data and the
      potential functional variant, rs11200638, which extended the ARMS2/HTRA1 region
      by 85.2 kb, were genotyped. Associations were tested using single-SNP and
      haplotype analyses. RESULTS: Statistically significant associations were found
      for six of the 19 SNPs with both typical nAMD and PCV (P < 1 * 10(-3)), peaking
      at a segment containing three of the SNPs: rs3793917, rs10490924, and rs11200638
      (P < 10(-7)). Six common haplotypes were inferred from the nine SNPs spanning 33
      kb, which included the six SNPs associated with both phenotypes. Among the six
      common haplotypes, one showed a positive association with typical nAMD, and two,
      including the one mentioned above, were associated with PCV. In addition, they
      corresponded to the risk alleles rs10490924 and rs11200638. CONCLUSIONS: The
      association pattern and haplotype estimation in the ARMS2/HTRA1 region of
      Japanese patients with PCV were very similar to those of Japanese patients with
      typical nAMD. The polymorphisms responsible for nAMD and PCV may be located in
      this region or in the strong linkage disequilibrium of rs10490924 and rs11200638.

PMID- 21191726
TI  - A case of Fukuyama congenital muscular dystrophy associated with negative
      electroretinograms.

PMID- 21191727
TI  - Congenital toxoplasmosis mimicking microcephaly-lymphedema-chorioretinal
      dysplasia.

PMID- 21191728
TI  - Case of lattice corneal dystrophy due to L527R mutation in the TGFBI gene with
      asymmetric corneal opacity in eye laterality.

PMID- 21191729
TI  - Endogenous candida chorioretinitis in a healthy infant.

PMID- 21191730
TI  - Choroidal neovascularization in a child following laser pointer-induced macular
      injury.

PMID- 21191731
TI  - Spontaneous closure of a stage 2 macular hole without detachment of the posterior
      hyaloid.

PMID- 21191732
TI  - A case of eyelid schwannoma in a child.

PMID- 21191733
TI  - Orbital arteriovenous malformation.

PMID- 21191734
TI  - Diagnostic localization of ectopic parathyroid lesions: developmental
      consideration.
AB  - Parathyroid glands arise from the third and fourth pharyngeal pouches.
      Parathyroid lesions sometimes develop ectopically. The aim of this article is to
      illustrate the knowledge of pharyngeal apparatus development to assist with
      diagnostic localization of ectopic parathyroid lesions. We retrospectively
      reviewed charts of 23 patients who received a diagnosis of ectopic parathyroid
      lesions. The ectopic lesions were widely distributed; cranially lesions were
      located on the carotid bifurcation, caudally in the right paraaortic region,
      ventrally on the surface of the sternohyoid muscle, and dorsally in the
      paraesophageal region. In most cases, parathyroid tissues were associated with
      structures related to the third or fourth pharyngeal pouches that traveled to
      regions where the ectopic lesions ultimately developed. In a few cases, lesions
      were not associated with these pouches and might have developed from parathyroid
      tissue that migrated due to an anomalous pathway of parathyroid travel. When
      patients present without entopic lesions, the presence of ectopic lesions should
      be evaluated based on an understanding of the developmental mechanisms of
      parathyroid glands and the frequency with which ectopic lesions have been found
      in specific locations. Systematic diagnosis can minimize the frequency with which
      ectopic lesions are missed during clinical care and maximize their accurate
      localization.

PMID- 21191735
TI  - Hepatic computed tomography perfusion: comparison of maximum slope and dual-input
      single-compartment methods.
AB  - PURPOSE: The aim of the study was to compare two analytical methods-maximum slope
      (MS) and the dualinput single-compartment model (CM)-in computed tomography (CT)
      measurements of hepatic perfusion and to assess the effects of extrahepatic
      systemic factors. MATERIALS AND METHODS: A total of 109 patients underwent
      hepatic CT perfusion. The scans were conducted at the hepatic hilum 7-77 s after
      administration of contrast material. Hepatic arterial perfusion (HAP) and portal
      perfusion (HPP) (ml/min/100 ml) and the arterial perfusion fraction (APF, %) were
      calculated with the two methods, followed by correlation assessment. Partial
      correlation analysis was used to assess the effects on hepatic perfusion values
      by various factors, including age, sex, risk of cardiovascular disease,
      compensation for respiratory misregistration, arrival time of contrast material
      at the abdominal aorta, transit time from abdominal aorta to hepatic parenchyma,
      and liver dysfunction. RESULTS: The mean HAPs, HPPs, and APFs were, respectively,
      31.4, 104.2, and 23.9 for MS and 27.1, 141.3, and 22.1 for CM. HAP and APF showed
      significant (P<0.0001) and moderate correlation (gamma=0.417 and 0.548) and HPP
      showed poor correlation (gamma=0.172) between the two methods. While MS showed
      weak correlations (gamma=-0.39 to 0.34; P<0.001 to <0.02) between multiple
      extrahepatic factors and perfusion values, CM showed weak correlation only
      between the patients' sex and HAP (gamma=0.31, P=0.001). CONCLUSION: Hepatic
      perfusion values estimated by the two methods are not interchangeable. CM is less
      susceptible to extrahepatic systemic factors.

PMID- 21191736
TI  - Magnetic resonance angiography of fetal vessels: feasibility study in the sheep
      fetus.
AB  - PURPOSE: The aim of this study was to perform fetal magnetic resonance
      angiography (MRA) in utero in a sheep model. MATERIAL AND METHODS: Images of the
      great vessels, the heart, and the tracheal tree were performed on four pregnant
      ewes with a 1.5-T scanner (Philips Medical Systems, Best, The Netherlands). MRA
      was achieved in utero using a nontriggered free-breathing three-dimensional
      balanced fast field echo (FFE) technique. All obtained MRA images were evaluated
      in consensus on a three-point scale by two radiologists with 9 and 4 years of
      experience in fetal MRI, respectively. RESULTS: The fetal heart frequencies were
      between 130 and 160 bpm. The aorta from the aortic bulb to the bifurcation as
      well as some of the main aortic branches could be depicted. The pulmonary trunk
      and arteries, the superior and inferior caval veins, and the subsegmental
      branches of the trachea could also be visualized. CONCLUSION: The nontriggered
      MRA of the fetal great vessels with images of the tracheal tree allowed an
      excellent evaluation of anatomical structures.

PMID- 21191737
TI  - Interobserver agreement on the diagnosis of bowel ischemia: assessment using
      dynamic computed tomography of small bowel obstruction.
AB  - PURPOSE: The aim of this study was to evaluate the accuracy and interobserver
      variability of dynamic computed tomography (CT) for diagnosis of small bowel
      obstruction. METHOD AND MATERIALS: A total of 115 patients with a CT diagnosis of
      small bowel obstruction were included. Two radiologists and two residents
      performed blinded, independent, retrospective reviews of CT studies. Attention
      was focused on the presence of reduced early enhancement of the bowel wall and
      closed loop obstruction. Results were correlated with surgical findings in 15
      cases and clinical follow-up in 100 cases. Sensitivity and specificity were
      calculated, and kappa statistics were used to analyze interobserver agreement.
      RESULTS: In all, 13 cases were surgically confirmed small bowel ischemia.
      Sensitivity, specificity, positive predictive value, and negative predictive
      value for the diagnosis of ischemia were 85%, 96%-97%, 73%-79%, and 97%-98%,
      respectively, for radiologists and 69%-93%, 93%-95%, 63%-64%, and 96%-99%,
      respectively, for residents. For agreement in the interpretations of reduced
      early enhancement of bowel wall, closed loop obstruction, and presence of bowel
      ischemia, the values were 0.62, 0.71, and 0.80, respectively, between
      radiologists and 0.57-0.70, 0.63-0.74, and 0.56-0.68, respectively, between
      radiologists and residents. CONCLUSION: There was moderate or substantial
      agreement for the diagnosis of small bowel ischemia between radiologists and
      residents. However, there was substantial agreement for the presence of closed
      loop obstruction.

PMID- 21191738
TI  - Semiquantitative measurement of pulmonary hilar gallium-67 uptake using single
      photon emission computed tomography/computed tomography for the diagnosis of
      autoimmune pancreatitis.
AB  - PURPOSE: We ascertained the difference in the level of pulmonary hilar (PH)
      gallium-67 (Ga-67) uptake in autoimmune pancreatitis (AIP) patients between the
      active (before corticosteroid therapy) and remittent (after 4 weeks of
      corticosteroid therapy) phases using a semiquantitative measurement method based
      on single photon emission computed tomography (SPECT) with integrated low-dose
      computed tomography (CT). MATERIALS AND METHODS: Ga-67 planar scans and SPECT
      were performed in 11 AIP patients before and after 4 weeks of corticosteroid
      therapy. A region of interest (ROI) was drawn over the bilateral pulmonary hilum
      and the liver, and average counts of the pulmonary hilum and liver were
      calculated. The average counts of the pulmonary hilum divided by those of the
      liver gave the pulmonary hilum/liver ratio (H/L). RESULTS: A significant
      difference was observed in the H/L between active and remittent phases. H/L in
      the active phase was 1.03+/-0.32 and that in the remittent phase was 0.58+/-0.25
      (t-test, P=0.0016). CONCLUSIONS: PH Ga-67 uptake in patients with active AIP was
      semiquantitatively higher than that in those with remittent AIP. Hence, this may
      be a useful finding for an early diagnosis, estimating the effectiveness of
      corticosteroid therapy, and following up patients with this disease.

PMID- 21191739
TI  - Computed tomography-based three-dimensional dosimetry of intracavitary
      brachytherapy for cervical cancer.
AB  - PURPOSE: The aim of this study was to show the results of computed tomography
      (CT)-based dosimetry of intracavitary brachytherapy for cervical cancer.
      MATERIALS AND METHODS: A total of 20 patients with cervical cancer underwent
      intracavitary brachytherapy with external beam radiation therapy. The prescribed
      dose of brachytherapy was 6 Gy per fraction to point A. In every fraction a CT
      scan was performed after applicator insertion and three-dimensional (3D)
      dosimetry was done. The tumor dose was evaluated using D90 (the minimum dose
      delivered to 90% of the volume), and the doses of risk organs were evaluated
      using D2cc (the minimum dose in the most irradiated 2 cm3 of the volume).
      RESULTS: The mean D90 for the clinical target volume (CTV) was 7.0 Gy (range 4.8
      9.8 Gy). There was a negative correlation between the volume and the D90 for the
      CTV. The mean D2cc doses for the rectum and bladder were 6.0 Gy (range 3.9-9.0
      Gy) and 6.5 Gy 5 Gy 2.9-9.0 Gy), respectively. CONCLUSION: CT-based 3D dosimetry
      of intracavitary brachytherapy for cervical cancer was useful for evaluating the
      doses of the CTV and the organs at risk. In cases with a large CTV, CTV D90 was
      often lower than the point A dose, and modulation of the prescribed dose might
      have to be considered.

PMID- 21191740
TI  - Assessment of cerebral perfusion from bypass arteries using magnetic resonance
      regional perfusion imaging in patients with moyamoya disease.
AB  - PURPOSE: The purpose of this study was to evaluate whether cerebral perfusion
      from bypassed arteries can be demonstrated on regional perfusion imaging (RPI)
      using arterial spin labeling. We then compared cerebral perfusion on RPI and
      digital subtraction angiography (DSA) in moyamoya patients who underwent
      extracranial-intracranial bypass surgery. MATERIALS AND METHODS: We performed RPI
      using a 3-T magnetic resonance scanner and DSA studies in 11 moyamoya patients
      treated by bypass surgery. For RPI we placed a selective labeling slab on the
      bypassed external carotid artery. Two neuroradiologists determined the extent and
      location of the cerebral perfusion from bypass arteries in the middle cerebral
      artery territories on RPI and DSA. Kappa analysis was used to assess the
      interobserver agreement with respect to the extent and location of the cerebral
      perfusion and to evaluate the intermodality agreement between RPI and DSA.
      RESULTS: Interobserver agreement for the extent of cerebral perfusion on RPI was
      very good (kappa=0.89), with excellent location (kappa=1.00). Intermodality
      agreement for the extent of perfusion was very good (kappa=0.89), with good
      location (kappa=0.74). CONCLUSION: RPI is useful for evaluating cerebral
      perfusion from bypass arteries in moyamoya patients.

PMID- 21191741
TI  - Obstructive jaundice caused by a portal cavernoma.
AB  - A 69-year-old Japanese man was admitted to our hospital because of acute
      cholangitis with biliary obstruction. The cause of obstruction was either
      compression by a portal cavernoma or cavernous transformation. Multidetector row
      computed tomography (MDCT) and abdominal ultrasonography (US) revealed a portal
      cavernoma around the common bile duct. Magnetic resonance
      cholangiopancreatography (MRCP) and endoscopic retrograde cholangiography (ERC)
      demonstrated characteristic short, smooth narrowing of the bile duct. Endoscopic
      US and intraductal US demonstrated collateral vessels around the bile duct and
      were helpful for ruling out a neoplastic lesion. Thus, a combination of imaging
      modalities was useful for diagnosing this hepatobiliary complication, portal
      biliopathy.

PMID- 21191742
TI  - Whole-body 18F-fluorodeoxyglucose positron emission tomography/computed
      tomography images before and after chemotherapy for Kaposi sarcoma and highly
      active antiretrovirus therapy.
AB  - Kaposi sarcoma is an acquired immunodeficiency syndrome-related disease that
      mainly involves the skin, gastrointestinal gut, and lungs. Whole-body 18F
      fluorodeoxyglucose-positron emission tomography and computed tomography (FDG
      PET/CT) scanning is useful for simultaneous detection of multiple lesions of
      Kaposi sarcoma. We present a 67-year-old man with a history of infection with
      human immunodeficiency virus who presented with numerous cutaneous lesions. FDG
      PET/CT images showed lesions in the skin, lung, and lymph nodes. The
      gastrointestinal lesions were detected using gastric fiberscopy (GF) and colon
      fiberscopy (CF). After Kaposi sarcoma therapy, the uptake in the lesions of the
      skin, lung, and lymph nodes decreased, but new lesions were detected in the
      pancreas and lumbar spine. He had pancreatitis and Candida spondilitis. Whole
      body FDG-PET/CT is useful for detecting lesions and determining the extension to
      which the disease has spread, adding the gastrointestinal lesions by GF and CF.
      After therapy, FDG-PET/CT can be used to demonstrate which lesions remain active
      and to determine the overall response to treatment. In this case, we show how
      useful FDG-PET/CT is and how difficult it is to treat Kaposi sarcoma.

PMID- 21191744
TI  - Coil embolization of a celiac artery aneurysm using the neck remodeling
      technique.
AB  - Aneurysms of the celiac trunk are rare. Untreated lesions enlarge progressively
      and may rupture spontaneously. We report the case of a 56-year-old man whose wide
      neck celiac aneurysm was successfully packed with coils with preservation of the
      native arterial circulation by percutaneous transcatheter embolization using the
      neck remodeling technique.

PMID- 21191743
TI  - Myocardial hypoenhancement in a case of acute coronary syndrome with normal
      coronary arteries: demonstration by 64-slice multidetector computed tomography.
AB  - A 48-year-old man presented with severe chest pain that had started 2 h before
      and ST elevation on the electrocardiogram. Cardiac computed tomography (CT) was
      performed using a 64-slice multidetector scanner (MDCT) to assess coronary artery
      stenosis at 3 h after the onset. Coronary CT angiography showed no significant
      stenosis at the coronary arteries, but CT myocardial images at systole
      demonstrated predominantly subendocardial hypoenhancement in the anterior wall.
      Cardiac CT that combined coronary angiography and myocardial imaging demonstrated
      myocardial hypoenhancement in a case of acute coronary syndrome with normal
      coronary arteries, which may be related to microvascular dysfunction caused by
      vasospastic angina or microvascular angina.

PMID- 21191745
TI  - Accuracy of determining preoperative cancer extent measured by automated breast
      ultrasonography.
AB  - PURPOSE: The aim of this study was to determine the accuracy of measuring
      preoperative cancer extent using automated breast ultrasonography (US). MATERIALS
      AND METHODS: This retrospective study consisted of 40 patients with
      histopathologically confirmed breast cancer. All of the patients underwent
      automated breast US (ABVS; Siemens Medical Solutions, Mountain View, CA, USA) on
      the day before the surgery. The sizes of the lesions on US were measured on
      coronal multiplanar reconstruction images using the ABVS workstation.
      Histopathological measurement of tumor size included not only the invasive foci
      but also any in situ component and was used as the gold standard. The discrepancy
      of the tumor extent between automated breast US and the histological examination
      was calculated. RESULTS: Automated breast US enabled visualization of the breast
      carcinomas in all patients. The mean size of the lesions on US was 12 mm (range 4
      62 mm). The histopathological diagnosis was ductal carcinoma in situ (DCIS) in
      seven patients and invasive ductal carcinoma in 33 patients (18 without an
      intraductal component, 15 with an intraductal component). Lesions ranged in
      diameter from 4 to 65 mm (mean 16 mm). The accuracy of determination of the tumor
      extent with a deviation in length of <2 cm was 98% (39/40). CONCLUSION: Automated
      breast US is thought to be useful for evaluating tumor extent preoperatively.

PMID- 21191746
TI  - p53 functional activation is independent of its genotype in five esophageal
      squamous cell carcinoma cell lines.
AB  - p53 mutations have been found in many esophageal squamous cell carcinoma (ESCC)
      clinical specimens and cell lines. We reasoned that functional inactivation of
      wild-type p53 or the functional activation of mutant-type p53 might exist in
      these specimens and cell lines. In this study, we identified the correlation
      between p53 functional activation and its genotype in five different ESCC cell
      lines. To examine the potential p53 activation in a certain ESCC cell line, DNA
      damage methods including X-ray exposure and cisplatin treatment were employed to
      treat cells. Further, the expression of p53 protein and four transcripts of well
      known p53 target genes were investigated using Western blot and reverse
      transcriptionpolymerase chain reaction (RT-PCR) after cell exposure to DNA
      damage. The results showed that in KYSE 30 cell line with mutant p53 and KYSE 150
      with wild-type p53, p53 could be activated by DNA damages. However, p53 could not
      be activated following the DNA damages in YES 2 with wild-type p53, KYSE 70 with
      mutant p53, and EC9706 with unknown p53 genotype. All our data indicated that p53
      function in certain cells is not closely correlated with its genotype. To judge
      p53 function in a particular cell line, it is important to examine the p53
      functional activation, but not to simply rely on the p53 genotype.

PMID- 21191747
TI  - Influence of the adjuvant therapy on the survival of patients with stage II
      pancreatic carcinoma.
AB  - This study aimed to investigate the effect of adjuvant therapy on the treatment
      of stage II pancreatic carcinomas. The clinical data of 139 cases of stage II
      pancreatic carcinoma were analyzed retrospectively. The overall 1-, 3-, and 5
      year cumulative survival rates of 139 patients were 40%, 6%, and 3%,
      respectively, and the median survival time (MST) was 279 days. The MST was 399
      days for those with adjuvant therapy, 210 days for those without adjuvant
      therapy, 390 days for the radical resection group, 270 days for the bypass
      operation and laparotomy group, and 132 days for the nonsurgical group. The
      adjuvant therapy could not prolong the survival time and decrease the liver
      metastasis rate of the patients with stage II carcinoma significantly in radical
      resection group (P>0.05). In the bypass operation and laparotomy group and
      nonsurgical group, the adjuvant therapy could improve the survival of the
      patients significantly (P<0.05); however, the survival rate was not significantly
      different among systemic venous chemotherapy, radiation therapy, interventional
      therapy, and combination therapy (P>0.05); or between gemcitabine (GEM) regimen
      and 5-fluorouracil regimen (P>0.05); or between GEM monotherapy and GEM combined
      with platinum/capecitabine (P>0.05). The proper adjuvant therapy can be suggested
      according to the general condition of the patients after radical resection for
      stage II pancreatic carcinoma. Chemotherapy combined with radiation should be
      applied actively for the patients whose cancerous tissues were not radically
      resected. The clinical efficacy of GEM combined with platinum/capecitabine is
      relatively better than GEM.

PMID- 21191748
TI  - Serum carbohydrate antigen (CA) 19-9 as a prognostic factor in
      cholangiocarcinoma: a meta-analysis.
AB  - This study was performed to determine the prognostic role of preoperative serum
      carbohydrate antigen (CA) 19-9 levels in the survival of patients with
      cholangiocarcinoma. Articles published up to June 1(st), 2010 that evaluated
      preoperative CA19-9 levels and the prognosis of cholangiocarcinoma were collected
      for meta-analysis. The required information for calculating individual relative
      risk (RR) was extracted from the studies, and a combined overall RR was
      estimated. Nine eligible studies were included. One study dealt with extra
      hepatic cholangiocarcinoma, while the other eight studies analyzed intra-hepatic
      cholangiocarcinoma. The mean methodological quality score was 74.1%, ranging from
      65.5% to 82.5%. The overall RR for the nine studies was 1.28 (95% confidence
      interval = 1.10-1.46), and the Z-score for overall effect was 13.83 (P<0.001).
      The association between serum CA19-9 level and lymph node involvement was also
      assessed. The combined RR was 1.471 (95% confidence interval = 0.411-5.264) and Z
      score for overall effect was 0.59 (P = 0.553). CA19-9 levels were associated
      significantly with the prognosis of patients with cholangiocarcinoma. This meta
      analysis shows that elevation of preoperative CA19-9 levels is correlated with a
      poor prognosis of patients with cholangiocarcinoma. However, larger scale and
      randomized studies are needed to draw a more substantive conclusion.

PMID- 21191750
TI  - Metabolism study of botanical drugs.

PMID- 21191751
TI  - Control of autophagy with small molecules.
AB  - Autophagy is the mass degradation system that removes long-lived proteins and
      malfunctioning organelles within the cell. Dysfunctional autophagic processes can
      cause various diseases such as cancer and neurodegenerative disorders, but the
      underlying mechanisms responsible for such events remain undefined. Small
      molecules that control autophagy could be powerful tools to reveal autophagy
      mechanisms, and to develop treatments for autophagy-related diseases including
      Alzheimer's disease, Parkinson's disease and various cancer types. This review
      discusses the small molecules that have been identified to control autophagy and
      how they can be used to understand signaling pathways important for autophagy in
      the context of chemical genomics.

PMID- 21191752
TI  - Synthesis and antimicrobial activity of novel 5-amino-4-cyano-1H-pyrazole and
      quinazolin-4(3H)-one derivatives.
AB  - New substituted aroylhydrazones (4a-f) were synthesized from the acid hydrazide
      (3) and the corresponding aldehyde or aldose. 5-Amino-4-cyano-1H-pyrazole
      derivatives (6a-f) were prepared by the reaction of the aroylhydrazones (4a-f)
      with malononitrile. The synthesized compounds were tested for antimicrobial
      activity against various bacteria and fungi and showed moderate to high
      inhibition activities. Compounds incorporating a sugar moiety as well as a
      pyrazolyl ring in their structure displayed the highest antimicrobial activity.

PMID- 21191753
TI  - Synthesis, characterization and biological activity of a series of carboxamide
      derivatives of ofloxacin.
AB  - The present study was designed to help develop new agents with better
      antimicrobial profiles. Specifically, we focused on modification of the basic
      structure of ofloxacin by introducing new functionality at its C3 position. For
      this purpose, the carboxylic group at the C3 position of ofloxacin was replaced
      by an amide group through an ester aminolysis reaction. The structure of these
      derivatives was established by various analytical techniques i.e., IR, (1)H-NMR,
      (13)C-NMR CHNS elemental analysis and mass spectrometry. The antibacterial
      activity of ofloxacin and its derivatives against ten different Gram-positive and
      Gram-negative microorganisms was studied using a disk susceptibility method.
      These compounds were further tested for their activity against various fungi and
      compared to ofloxacin. The synthesized compounds showed diverse antimicrobial
      profiles. Among them, a few compounds possessed a comparable or better activity
      in comparison to the reference drug.

PMID- 21191754
TI  - Synthesis and antimicrobial activity of 1,2,3-triazoles containing quinoline
      moiety.
AB  - A new series of substituted 1,2,3-triazoles (4a-n) were synthesized from 4-azido
      2,8-bistrifluoromethylquinoline 2. The 1,3-dipolar cycloaddition reaction of 2
      with ethyl acetoacetate afforded 1-(2,8-Bistrifluoromethylquinolin-4-yl)-5-methyl
      1,2,3-triazole-4-carboxylic acid 3, which was then converted into its
      corresponding acid hydrazide 3a. Condensation of this hydrazide with different
      aromatic aldehydes resulted in the formation of Schiff's bases, N-[1
      Arylmethylene]-1-[2,8-bistrifluoromethylquinoline-4-yl]-5-methyl-1H-1,2,3
      triazole-4-carbohydrazides (4a-n). These newly synthesized 1,2,3-triazole
      derivatives were characterized by analytical and spectral data. All the
      synthesized compounds were evaluated in vitro for their antibacterial and
      antifungal activity. A brief investigation of the structure activity
      relationships revealed that the nature of the substituent on position 4 of the
      triazole ring influences the antimicrobial activity. Among the newly synthesized
      compounds, the most active compound was 4n, which contained the 3-methylthien-2
      yl moiety and showed a broad spectrum of antimicrobial activity against all the
      strains used for testing. Compounds 4b, 4c, 4e, 4f, 4h and 4l showed significant
      antimicrobial activity at the concentration of 6.25 MUg/mL.

PMID- 21191755
TI  - Synthesis and characterization of novel unnatural bichalcones.
AB  - Five bichalcones (5-1 ~ 5-4, 9) were prepared by the reaction of biphenyl-4,4'
      dicarbaldehyde (4) and 4,4'-dioxybenzaldehyde (8) with the respective
      acetophenone analogs via Claisen-Schmidt condensation and were then fully
      identified by 1H-NMR, (13)C-NMR and mass analyses.

PMID- 21191756
TI  - A new triterpene and an antiarrhythmic liriodendrin from Pittosporum brevicalyx.
AB  - A new triterpene, 21-O-senecioyl-R(1)-barrigenol (1) and 13 known compounds were
      isolated from the ethanol extracts of the leaves and bark of Pittosporum
      brevicalyx (Oliv.) Gagnep. Their structures were elucidated based on spectral
      data. The antiarrhythmic action of one furofuran lignan, liriodendrin (2), was
      tested on a model of CaCl(2)-induced arrhythmia and compared with the effect of
      verapamil. The prophylactic administration of liriodendrin (2) was effective in
      prolonging latency of arrhythmia and reducing the occurrence of ventricular
      fibrillation from 75% to 25%. The overall mortality rate was significantly
      reduced by the prophylactic administration of liriodendrin from 87.5% to 25%. The
      antiarrhythmic effect of liriodendrin (5.0 mg/kg) was similar to that of
      verapamil (1.05 mg/kg). Thus, liriodendrin may be a potent suppressor of CaCl(2)
      induced arrhythmias.

PMID- 21191757
TI  - Two new triterpenoid acids from Kadsura coccinea.
AB  - An investigation of EtOAc extracts of Kadsura coccinea (Lem.) A. C. Smith, has
      led to the isolation of two new compounds characterized as 3-hydroxy-12-hydroxyl
      coccinic acid (1) and 3-hydroxy-neokadsuranic acid A (2). Their structures were
      established by 1D and 2D NMR techniques and mass spectroscopy. Antiproliferative
      effects of the isolated compounds were evaluated against four human tumor cell
      lines (A549, HCT116, HL-60 and HepG2), and it was found that compound 1 exhibited
      antiproliferative effects with IC(50) values ranging from 3.01 to 18.08 MUg/mL.

PMID- 21191758
TI  - A potential inhibitor of rat aortic vascular smooth muscle cell proliferation
      from the pollen of Typha angustata.
AB  - By various chromatographic methods, three flavonoids, (2S)-naringenin (1),
      isorhamnetin 3-O-(2-O-alpha-L-rhamnopyranosyl) beta-D-glucopyranoside (2),
      typhaneoside (3), and two sterol glycosides, beta-sitosterol-3-O-(6-octadecanoyl)
      beta-D-glucopyranoside (4) and beta-sitosterol-3-O-(6-octadeca-9Z,12Z-dienoyl)
      beta-D-glucopyranoside (5), were isolated from the pollen of Typha angustata.
      Their structures were determined on the basis of spectroscopic analyses. The
      flavonoids (1-3) were evaluated for their effects on the viability and
      proliferation of rat aortic smooth muscle cells. (2S)-naringenin (1)
      significantly inhibited cell proliferation in a dose-dependent manner without
      cytotoxic at concentrations of 30, and 50 MUM; it reduced the number of cells
      following PDGF-BB treatment to 1.83 +/- 0.30 * 10(4) and 2.20 +/- 0.60 * 10(4)
      cells/well, respectively. These findings suggest that (2S)-naringenin has
      antiproliferative effects on aortic smooth muscle cells.

PMID- 21191759
TI  - Biological activities of Fructus arctii fermented with the basidiomycete Grifola
      frondosa.
AB  - Fructus arctii extract containing phenolic glycosides was cultured with Grifola
      frondosa mycelia to produce beta-glucosidase and its biological activities were
      studied. This beta-glucosidase converted the glycosides (arctiin and caffeic acid
      derivatives) into aglycones (arctigenin and caffeic acid). Fermented Fructus
      arctii extract (G-FAE) with G. frondosa had antioxidant and 5-lipoxygenase
      inhibitory activities. The photoprotective potential of G-FAE was tested in human
      dermal fibroblasts (HDF) exposed to ultra-violet A (UVA). It was revealed that G
      FAE had an inhibitory effect on human interstitial collagenase (matrix
      metalloproteinase, MMP-1) expression in UVA-irradiated HDF. The treatment of UVA
      irradiated HDF with G-FAE resulted in a dose-dependent decrease in the expression
      level of MMP-1 mRNA. G-FAE also showed notable stimulation of collagen
      biosynthetic activity for fibroblasts. These diverse functionalities suggest that
      G-FAE could be a promising cosmetic ingredient.

PMID- 21191760
TI  - Spirafolide from bay leaf (Laurus nobilis) prevents dopamine-induced apoptosis by
      decreasing reactive oxygen species production in human neuroblastoma SH-SY5Y
      cells.
AB  - Reactive oxygen species (ROS) are important mediators in many neurodegenerative
      diseases including Alzheimer's disease and Parkinson's disease. This study tested
      the neuroprotective effects of spirafolide, a compound purified from the leaves
      of Laurus nobilis L. (Lauraceae), against dopamine (DA)-induced apoptosis in
      human neuroblastoma SH-SY5Y cells. Following a 24-h exposure of cells to DA
      (final conc., 0.6 mM), we observed a marked increase in apoptosis, increased
      generation of ROS and decreased cell viability. Pretreatment of the cells for 24
      h with spirafolide (0.4, 2, and 10 MUM) before exposure to DA notably increased
      cell survival (p < 0.01) and lowered intracellular ROS levels (p < 0.01). These
      results indicate that spirafolide has neuroprotective effects against DA
      toxicity. These effects may contribute to the treatment of neurodegenerative
      diseases.

PMID- 21191761
TI  - Inhibitory effect of danazol on melanogenesis in mouse B16 melanoma cells.
AB  - In the present study, more than 200 generic drugs were screened to verify their
      applicability as a skin-lightening agent using mouse B16 melanoma cells. Of the
      numerous agents, danazol was found to inhibit melanogenesis in B16 cells in a
      dose-dependent manner with an IC(50) value of 9.3 MUM. In addition, danazol
      reduced cellular tyrosinase activity in B16 cells but did not directly inhibit
      the murine tyrosinase activity in the cell-free system. Western blotting analysis
      confirmed that danazol downregulated the levels of tyrosinase protein in B16
      cells, and reverse-transcription polymerase chain reaction (RT-PCR) analysis
      revealed that danazol did not downregulate the levels of tyrosinase mRNA in the
      cells. These results indicate that danazol inhibits melanogenesis in B16 cells
      via reducing the tyrosinase activity by post-transcriptional regulation.

PMID- 21191762
TI  - Cetirizine dihydrochloride loaded microparticles design using ionotropic cross
      linked chitosan nanoparticles by spray-drying method.
AB  - To control the release rate and mask the bitter taste, cetirizine dihydrochloride
      (CedH) was entrapped within chitosan nanoparticles (CS-NPs) using an ionotropic
      gelation process, followed by microencapsulation to produce CS matrix
      microparticles using a spray-drying method. The aqueous colloidal CS-NPs
      dispersions with a drug encapsulation efficiency (EE) of <15%, were then spray
      dried to produce a powdered nanoparticles-in-microparticles system with an EE of
      >70%. The resultant spherical CS microparticles had a smooth surface, were free
      of organic solvent residue and showed a diameter range of 0.5~5 MUm. The in vitro
      drug release properties of CedH encapsulated microparticles showed an initial
      burst effect during the first 2 h. Drug release from the matrix CS microparticles
      could be retarded by the crosslinking agent pentasodium tripolyphosphate or the
      wall material. The technique of 'ionotropic gelation' combined with 'spray
      drying' could be applicable for preparation of CS nanoparticlesin-microparticles
      drug delivery systems. CS-NPs based microparticles might provide a potential
      micro-carrier for oral administration of the freely water-soluble drug--CedH.

PMID- 21191763
TI  - Pharmacokinetics, tissue distribution, metabolism, and excretion of ginsenoside
      Rg1 in rats.
AB  - The pharmacokinetics, tissue distribution, metabolism, and excretion of
      ginsenosides Rg(1) were studied in Wistar rats, by measuring the concentrations
      of Rg(1) and its metabolites in the blood, tissues, bile, urine, and feces after
      dosing. After intravenous (i.v.) administration, the elimination half-lives of
      Rg(1) and its metabolites were 1.82, 5.87, and 6.87 h, and the area under the
      curves were 1595.7, 597.5, and 805.6 ng.h/mL, respectively. After oral
      administration, the elimination half-lives of Rg(1) and its metabolites were
      2.25, 6.73, 5.44, and 5.06 h, and the area under the curves were 2363.5, 4185.5,
      3774.3, and 396.2 ng.h/mL, respectively. After i.v. administration, Rg(1) and its
      metabolites were well distributed to the tissues analyzed except for the brain.
      The maximum concentration of Rg(1) was reached in all tissues at 5 min post dose,
      and it was eliminated from most of the tissues except for the kidney faster than
      it was eliminated from the blood. The maximum concentration of the metabolites
      was reached in all tissues between 4 and 6 h post dose. After i.v.
      administration, the recovery of the Rg(1) prototype in the urine and bile was
      27.96% and 60.77%, respectively. The metabolism of Rg(1) in the intestine was via
      a hydrolization pathway, with the 6- and 20-glucoside bond hydrolyzed gradually
      under the catalysis of beta-glucosaccharase, and then the metabolites were
      reabsorbed into the blood. Finally, the total recovery of the Rg(1) prototype and
      its metabolites in the urine and feces were 51.31% and 47.46%, respectively.

PMID- 21191764
TI  - In vitro metabolism of jaceosidin and characterization of cytochrome P450 and UDP
      glucuronosyltransferase enzymes in human liver microsomes.
AB  - Jaceosidin is an active component in Artemisia species as well as Eupatorium
      species and it exhibits antiallergic, anticancer, antioxidant, anti-inflammatory,
      and antimutagenic activities. Jaceosidin was metabolized to jaceosidin
      glucuronide, 6-O-desmethyljaceosidin, hydroxyjaceosidin, 6-O-desmethyljaceosidin
      glucuronide, and hydroxyjaceosidin glucuronide in human liver microsomes. This
      study characterized the human liver cytochrome P450 (CYP) and
      UDPglucuronosyltransferase (UGT) enzymes responsible for the metabolism of
      jaceosidin. CYP1A2 was identified as the major enzyme responsible for the
      formation of 6-O-desmethyljaceosidin and hydroxyjaceosidin from jaceosidin on the
      basis of a combination of correlation analysis and experiments including immuno
      inhibition, chemical inhibition in human liver microsomes, and metabolism by
      human cDNA-expressed CYP enzymes. Jaceosidin glucuronidation was catalyzed by
      UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A9, and UGT1A10. These results suggest that
      the pharmacokinetics of jaceosidin may be dramatically affected by polymorphic
      CYP1A2, UGT1A1, and UGT1A7 responsible for the metabolism of jaceosidin or by the
      coadministration of relevant CYP1A2 or UGT inhibitors or inducers.

PMID- 21191765
TI  - 6-Alkylsalicylic acid analogues inhibit in vitro ATPase activity of heat shock
      protein 90.
AB  - The molecular chaperone heat shock protein 90 (Hsp90) is responsible for
      maintaining the correct folding and stability of many signaling proteins. It is a
      promising target of cancer therapeutics and several other diseases, including
      neurodegenerative disease, nerve injuries, inflammation, and infection. In an
      effort to identify new Hsp90 inhibitors from natural sources using an in vitro
      ATPase inhibition assay, two 6-alkylsalicylic acid analogues, salaceyin A and B
      were identified from the culture extract of Streptomyces. Salaceyin A and B
      exhibited moderate ATPase inhibitory activities with IC(50) values of 68.3 and
      65.2 MUM, respectively. Binding of salaceyins to human Hsp90alpha was examined by
      competition binding experiments with ATP-Sepharose beads. However, the compounds
      exhibited no degradation activity of Hsp90 client proteins, Her2, c-Raf, or Akt.

PMID- 21191766
TI  - pH-independent sustained release matrix tablet containing doxazosin mesylate:
      effect of citric acid.
AB  - The aim of this study was to develop a pH-independent sustained release matrix
      tablets of doxazosin mesylate. The matrix tablets were prepared by direct
      compression technique using polyethylene oxide, sodium alginate and citric acid
      as a pH modifier. Formulations were evaluated for an in vitro drug release study,
      erosion study, and the microenvironmental pH was studied using the pH indicator
      methyl red. For formulations without citric acid, the extent and rate of drug
      release in simulated gastric fluid were much higher than those in simulated
      intestinal fluid. By adding the citric acid, the drug release rate in simulated
      intestinal fluid was increased, and microenvironmental pH values within the
      tablets were maintained at low pH during drug release. Furthermore, drug release
      from the matrix tablet containing 20% w/w citric acid was comparable to that from
      a commercial product, Cardura(r) XL, and a pH-independent release could be
      achieved. Therefore, the incorporation of citric acid as a pH modifier to
      Polyethylene oxide-sodium alginate matrix tablets effectively produced pH
      independent doxazosin mesylate release profiles.

PMID- 21191768
TI  - Determination of the L-enantiomer of nateglinide in pharmaceutical formulations
      by micellar electrokinetic chromatography.
AB  - An analytical micellar electrokinetic chromatographic method was developed and
      validated for the determination of the L-enantiomer of nateglinide. Separations
      were carried out in a 50 MUm, 64.5/56 fused-silica capillary. The optimized
      conditions included 75 mM borate buffer, pH 9.2, containing 50 mM of sodium
      dodecyl sulfate and 25 mg/mL of methyl-beta-cyclodextrin as background
      electrolyte, an applied voltage of 20 kV and a temperature of 15, UV detector at
      210 nm. The assay was validated for the L-enantiomer of nateglinide. The limit of
      detection and quantification were 0.07 and 0.2% respectively. Intraday precision
      was ranged between 0.12 and 1.7%. Interday precision ranged between 0.73 and
      1.73%. The assay was applied to the determination of the L-enantiomer of
      nateglinide in pharmaceutical formulations.

PMID- 21191767
TI  - Inhibitory effects of phenolic compounds from needles of Pinus densiflora on
      nitric oxide and PGE2 production.
AB  - The needles of Pinus densiflora Siebold et Zuccarini, a representative Pinus
      species that grows in Korea, have been used in oriental traditional medicine as
      remedies for rheumatitis, hemorrhage, cancer, etc. Phytochemical examination of
      the needles of Pinus densiflora Siebold et Zuccarini led to the isolation of four
      lignans, one flavan-3-ol, two flavonols and one organic acid. They were
      identified as icariside E(4) (1), cupressoside A (2), schizandriside (3), (+)
      isolariciresinol (4), (+)-catechin (5), quercetin 3-O-beta-D-glucopyranoside (6),
      5,7,8,4'-tetrahydroxy-3-methoxy-6-methylflavone 8-O-beta-D-glucopyranoside (7)
      and (-)-shikimic acid (8). In order to evaluate the anti-inflammatory effects of
      these compounds, their inhibitory activities against nitric oxide and
      prostaglandin E(2) production in IFN-gamma- and lipopolysaccharide-stimulated RAW
      264.7 cells were examined.

PMID- 21191769
TI  - Absence of drug interaction between Hwang-Ryun-Hae-Dok-Tang and
      phenolsulfonphthalein.
AB  - Hwang-Ryun-Hae-Dok-Tang (HT; a standardized herbal formula consisting of extracts
      from Coptidis Rhizoma, Scutellariae Radix, Phellodendri Cortex, and Gardeniae
      Fructus) was reported to modulate a function of multidrug resistance associated
      protein 2 (Mrp2) in vitro. The aim of this study was to assess the in vivo
      pharmacokinetic interactions between HT and phenolsulfonphthalein (PSP), a
      typical model Mrp2 substrate eliminated via bile through Mrp2 in rats. Rats
      received intravenous PSP (0.8 mg/kg) followed by either a single oral dose of HT
      (0.42 g/kg) or multiple oral doses of HT (0.42 g/kg for 7 days). The effect of HT
      treatment was also investigated at a steady-state after intravenous PSP infusion.
      In contrast to previous in vitro results, in this study, we found that the HT
      treated and control groups did not show any significant difference in the plasma
      PSP concentration and pharmacokinetic parameters, including area under the plasma
      concentration-time curve (AUC; control: 118 +/- 19, single dose: 116 +/- 40, and
      multiple dose: 137 +/- 4, in mg/(min.mL)) and biliary clearance (control: 3.15 +/
      0.69, single dose: 2.59 +/- 1.11, and multiple dose: 2.53 +/- 0.65, in
      mL/(min.kg)). However, cyclosporine A (5 mg/kg, an inhibitor of Mrp2)
      significantly decreased the AUC and biliary clearance of PSP. The steady-state
      plasma concentration and biliary clearance of PSP-were also similar between the
      groups. Taken together, our results suggest that HT may not be affected by Mrp2
      mediated herb-drug interaction in vivo.

PMID- 21191770
TI  - Crystal forms of SK-3530.
AB  - The objective of this work was to investigate the existence of polymorphs of SK
      3530 and the transformation of crystal forms. Two crystal forms of SK-3530 have
      been isolated by recrystallization and characterized by differential scanning
      calorimetry, powder X-ray diffractometry and thermogravimetric analysis. The
      differential scanning calorimetry and powder X-ray diffractometry patterns of two
      crystal forms were different respectively. After storage of 1 month at 0% RH
      (silica gel, 20 degrees C), 52% RH (saturated solution of
      Na(2)Cr(2)O(7).2H(2)O/20 degrees C) and 95% RH (saturated solution of
      Na(2)HPO(4)/20 degrees C), Form 2 was not transformed to Form 1 and two forms
      were shown to have a good physical stability at room temperature for 1 month. In
      the dissolution studies in pH 6.8 buffer at 37 +/- 0.5 degrees C, the dissolution
      rate of Form 2 was significantly higher than that of Form 1 under 30 min.

PMID- 21191771
TI  - Fever of unknown origin in children: a systematic review.
AB  - BACKGROUND: there are no previous systematic reviews of published pediatric case
      series describing the etiology of fever of unknown origin (FUO). The purpose of
      collecting these data is to determine the etiologies for children with FUO in
      both developing and developed countries. METHODS: the database Ovid Medline R
      (1950 to August 2009 week 4) and Ovid Embase (1980 to 2010 week 2) were used to
      conduct the search. Studies in any language were included if they provided the
      diagnosis in a series of 10 or more children with FUO. The diagnosis of each
      child at the time of publication of the study was recorded. RESULTS: there were
      18 studies that met the inclusion criteria, describing 1638 children. The
      diagnosis at the time of publication was malignancy for 93 children (6%),
      collagen vascular disease for 150 (9%), miscellaneous non-infectious conditions
      for 179 (11%), infection for 832 (51%), and no diagnosis for 384 (23%). There
      were 491 bacterial infections (59% of all infections) with common diagnoses being
      brucellosis, tuberculosis, and typhoid fever in developing countries,
      osteomyelitis, tuberculosis, and Bartonellosis in developed countries, and
      urinary tract infections in both. For children with no diagnosis after
      investigations, most had fever that ultimately resolved with no sequelae.
      CONCLUSIONS: about half of FUOs in published case series are ultimately shown to
      be due to infections with collagen vascular disease and malignancy also being
      common diagnoses. However, there is such a wide variety of possibilities that
      investigations should primarily be driven by the clinical story.

PMID- 21191772
TI  - Percentile curves for fat patterning in German adolescents.
AB  - BACKGROUND: because the body composition of adolescents varies more than that of
      adults and anthropometric parameters are regularly used for pediatric body fat
      measurements, we developed age-, gender-, and ethnicity-specific reference values
      for waist circumference (WC), hip circumference (HC), waist-to-height ratio
      (WHtR), waist-to-hip ratio (WHR), and skinfold thickness (SFT) in German
      adolescents. METHODS: a representative sample of 1633 boys and 1391 girls aged 12
      18 years participated in this cross-sectional study. Weight, height, body mass
      index (BMI), WC, HC, WHR, WHtR, and SFT were measured and smoothed; age-, gender
      , and ethnicity-specific reference curves were developed using the LMS method.
      RESULTS: females were significantly heavier than males at 12 years. Beyond age 14
      males were significantly heavier and taller than females. The SFT sum increased
      continuously (+20%) in females and was significantly higher (7.4 mm) than in
      males. At the 90th percentile, SFTtriceps decreased (-12%) in males but increased
      (+11%) in females; SFT(subscapular) increased in both genders. From 12 to 18
      years, WHtR and WHR remained constant, whereas WC and HC increased in both
      genders. WHtR was the best predictor for abdominal obesity in males (area under
      the curve [AUC] 0.974 +/- 0.004) and females (AUC 0.986 +/- 0.003), followed by
      body fat percentage (AUC 0.937 +/- 0.008) in males and WHR (AUC 0.935 +/- 0.009)
      in females. CONCLUSION: these age- and gender-specific percentile curves for SFT,
      WC, HC, WHR, and WHtR, derived from a large national sample of German
      adolescents, may be useful for developing international reference values for
      waist circumference and other predictors of adult obesity.

PMID- 21191773
TI  - Dendritic cells modification during sublingual immunotherapy in children with
      allergic symptoms to house dust mites.
AB  - BACKGROUND: the importance of dendritic cells (DCs) in the initiation of the Th2
      mediated inflammatory response to allergens is well known and more recently it
      has been proposed that DCs have a pivotal role in maintaining tolerance to
      allergens. The aim of this study was to investigate whether the success of
      sublingual immunotherapy (SLIT) in allergic asthma is mediated by the induction
      of changes of DCs functions. METHODS: ten children with allergic asthma sensitive
      to house dust mite were studied before and after 12 months of SLIT. Immature DCs
      were derived from peripheral blood monocytes cultured for 6 days in presence of
      interleukin (IL)-4 and GM-CSF and stimulated with lipopolysaccharide for the last
      24 hours to induce maturation. RESULTS: after 12 months of SLIT, mature DCs
      derived from SLIT-treated patients showed a statistically significant defect of
      CD86 up-regulation, an increase of IL-10, and a reduction of IL-12 production.
      CONCLUSION: SLIT induces changes in DCs functions that might be responsible for
      an impairment of T cell activation or drive T cells towards a regulatory
      activity, thus restoring immune tolerance to allergens.

PMID- 21191774
TI  - Effect of activity and television viewing on BMI z-score in early adolescents in
      Turkey.
AB  - BACKGROUND: television, computer and other causes of increased inactivity are
      reported to be among the major causes of obesity. This cross-sectional study was
      aimed to evaluate the effect of television viewing and other daily activities on
      body mass index (BMI) z-score of early adolescents. METHODS: a total of 860
      students and their parents (581) from different socioeconomic level schools were
      included. They were instructed to fill in a self-designed questionnaire. Weight
      and height were measured, and BMI z-scores were calculated. RESULTS: BMI z-score
      was higher in boys and in those attending high socioeconomic level schools.
      Children with a BMI z-score >2SD watched television (2.5 +/- 0.9 h/day) longer
      than those with <-2SD (1.6 +/- 0.8 h/day) (P=0.027). The three categories (<-2SD,
      -2SD-2SD, >2SD) differed significantly according to maternal (P<0.05) and
      paternal (P<0.005) BMI. Linear logistic regression analysis revealed that
      socioeconomic level, maternal BMI and paternal BMI are factors affecting BMI z
      score significantly. CONCLUSION: genetic and/or family environment which may
      affect the nutrition and activity of adolescents seems to be the most important
      factor affecting their BMI z-score.

PMID- 21191775
TI  - Epidemiologic and clinical characteristics of infectious mononucleosis associated
      with Epstein-Barr virus infection in children in Beijing, China.
AB  - BACKGROUND: infectious mononucleosis (IM) is a self-limited disease, but a few
      cases may have severe complications. This retrospective study was to explore the
      epidemiologic and clinical characteristics of IM associated with Epstein-Barr
      virus infection (EBV-IM) in children. METHODS: hospitalized patients with EBV-IM
      were enrolled during January 2005 to October 2008 in Beijing Children's Hospital
      Affi liated to Capital Medical University. All patients were divided into four
      groups: <1 year (group I), 1 to 3 years (group II), 3 to 6 years (group III), and
      >= 6 years (group IV). The epidemiology and clinical characteristics were
      compared among the four groups. RESULTS: totally 418 patients were enrolled, with
      245 boys and 173 girls. Fever, lymphadenopathy and pharyngitis were three main
      manifestations of the patients. The incidences of hepatomegaly, splenomegaly and
      rash were higher in the patients aged below 6 years, and with age increment the
      incidences lowered. In contrast, the patients aged <1 year had the lowest
      incidence of tonsillopharyngitis. The total white blood cell count was higher in
      the infantile group than in the other groups (P=0.038). The infantile group had
      significantly lower levels of serum alanine aminotransferase and aspartate
      aminotransferase than the older groups (P=0.007 and P=0.012 respectively). The
      percentage of CD4(+) T cell subset decreased and the percentage of CD8(+) T cell
      subset increased with age increment. CONCLUSIONS: the incidence of EBV-IM peaked
      in children at age of 4 to 6 years in Northern China. Most of the patients had
      the classic triad of fever, lymphadenopathy and pharyngitis. Clinical symptoms,
      signs, laboratory findings and complications of patients varied with ages.

PMID- 21191776
TI  - Steroid response in moderate to severe pediatric ulcerative colitis: a single
      center's experience.
AB  - BACKGROUND: we aimed to analyze clinical and inflammatory markers of steroid non
      response in patients with moderate/severe ulcerative colitis (UC) at the time of
      diagnosis. METHODS: this study included patients who were graded as having
      moderate/severe UC and received corticosteroids as first-line therapy.
      Demographic, clinical and laboratory findings and pediatric ulcerative colitis
      activity scores (PUCAS) were recorded. Response to corticosteroids was assessed
      30 days after the induction and long-term therapy. RESULTS: twenty-eight children
      were diagnosed as having moderate/severe UC. Their mean age +/- SD was 1 2.2 +/-
      4 years, and 17% were under 5 years of age. PUCAS at their initial admission was
      56.9 +/- 11.8. UC was observed at the left colon in 9 patients (32.1%), and
      pancolitis in 19 (67.9%). At the end of the 30th day, UC was completely remitted
      in 15 patients (53.5%), partially remitted in 2 (7.1%), and no response in 11
      (39.2%). Short-term follow-up showed partial remission in 2 patients, and overall
      remission with steroid in 17 (60.7%). Non-responders were given second-line
      treatment; steroid dependency was documented in 2 patients (7.1%) and another 2
      (7.1%) patients underwent colectomy. Predictors for steroid non-response were
      analyzed and only PUCAS at the initial admission was found to be associated with
      non-response to steroids (51.4 +/- 11.4 vs. 65.4 +/- 6.8, P<0.05). CONCLUSIONS:
      approximately half of the pediatric patients had complete response to steroid
      therapy in a long period. PUCAS could be used as a potential marker of "failed
      response" to steroid, but should be supported with a number of prospective
      randomized controlled studies.

PMID- 21191777
TI  - Maternal mental health in families of children with spina bifida.
AB  - BACKGROUND: this study aimed to compare mental health of mothers of children with
      spina bifida with mothers of able-bodied controls. METHODS: eighty-one mothers of
      children with spina bifida aged 1-18 years completed the General Health
      Questionnaire-12 (GHQ-12) and Parenting Stress Index Short Form (PSI/SF). The
      controls were 69 mothers of children with acute, non-disabling illnesses. Each
      child's adaptive skills were assessed using the Vineland Adaptive Behaviour
      Scales (VABS). Logistic regression analysis was used to determine factors related
      to a high GHQ score (>= 3) in all patients. RESULTS: compared to the controls,
      mothers of children with spina bifida had lower educational levels and were more
      likely to be the main caregivers and not working. Nineteen (23.5%) of them had a
      high GHQ score compared to 5 (7.2%) of the controls. They also had significantly
      higher scores for total PSI/SF and the parent domain, difficult child (DC) and
      parent-child dysfunctional interaction subscales. Children with spina bifida had
      lower scores for the composite VABS and communication, socialization, daily
      living skills and motor sub-domain than the controls. Spina bifida (odds ratio
      [OR] 4.3, 95% confidence interval [CI] 1.30-14.23), higher DC scores (OR 1.1, 95%
      CI 1.00-1.16), and higher life stress scores (OR 1.1, 95% CI 1.01-1.71) were
      associated with a high GHQ score. CONCLUSION: spina bifida, recent stressful life
      change events and maternal perception of a child as 'difficult' are associated
      with poor maternal psychological health.

PMID- 21191778
TI  - Long-term outcome of children after single-stage transanal endorectal pull
      through for Hirschsprung's disease.
AB  - BACKGROUND: single-stage transanal endorectal pull-through (TEPT) is a new
      technique for surgery of Hirschsprung's disease (HD). TEPT can be assisted by
      laparoscopy (laparoscopic assisted transanal pull-through, LATP) or with non
      additional procedure (total transanal endorectal pull-through, TTEP). This study
      was undertaken to evaluate the long-term outcome of these approaches in children
      with HD. METHODS: we retrospectively studied 131 patients (112 males and 19
      females) aged 7 days to 14 years who underwent single-stage TEPT from October
      2003 to July 2008. The medical records were reviewed for pre-, intra- and
      immediate post-operative complications. The data on stool pattern and
      complications were collected during the follow-up. Outcome was measured by
      continence evaluation score. RESULTS: no patients had intraoperative
      complications, but 5 had minor immediate postoperative complications. Late
      postoperative complications in 12 patients included enterocolitis (4 patients,
      one with severe enterocolitis died 7 months after operation), soiling (6) and
      constipation (2). There was a significantly higher frequency of stool in patients
      aged more than 36 months and those with a resected colon more than 30 cm
      (P<0.05). LATP showed significantly higher frequency of stool and soiling
      (P<0.05). Of the 54 patients who were older than 3 years at the time of follow
      up, continence score was normal in 10, good in 39, fair in 3, and poor in 2.
      Seventy-seven patients achieved good bowel control in 12.8 +/- 8.11 months after
      operation, 93.5 5% of whom within 24 months. Stool function was not improved in
      patients more than 30 months old after operation. CONCLUSIONS: the long-term
      outcome of single stage TEPT was excellent. There were few postoperative
      complications, and stool pattern improved gradually to an excellent level within
      24 months. Internal plication can be a good option for reducing the dilated
      proximal colon.

PMID- 21191779
TI  - Management of pediatric intussusception in general hospitals: diagnosis,
      treatment, and differences based on age.
AB  - BACKGROUND: age related differences in the management and outcomes of children
      with ileocolic intussusception have not been previously published. The purpose of
      this study is to compare the differences in diagnosis and treatment of pediatric
      ileocolic intussusception based upon age in general hospitals. METHODS: a review
      was made of pediatric patients treated for intussusception at 11 hospitals
      between 1996 and 2007. The patients were divided into 3 groups based on age:
      group A: <6 months (n=37), group B: 6 months to 4 years (n=126), group C: >4
      years (n=25). Diagnostic modality, operative reports, and hospital records were
      reviewed. RESULTS: altogether 188 patients were treated for ileocolic
      intussusception. Contrast enema was performed in 80.3% of the patients. Initial
      treatment for the patients included contrast enema in 80.3%, immediate operation
      in 3.2%, and others in 16.5%. Older patients were less likely to undergo a
      contrast enema (P<0.05) but more likely to be successfully reduced. Patients in
      group A had the lowest rate of successful reduction (P<0.05). Overall, 3.2% of
      the patients were taken to the operating room without any diagnostic evaluations,
      but 65% of the patients ultimately required operative intervention. Patients in
      groups A and C were more likely to undergo an operation (P<0.05). Rates of bowel
      resection and length of hospital stay were similar among the three groups.
      CONCLUSIONS: enema reduction for ileocolic intussusception is moderately
      successful in general hospitals and lower than that reported in children's
      hospitals. The lowest reduction rate occurs in patients of less than 6 months old
      and the diagnosis of intussusception in older children is rarely made by contrast
      enema. There is a higher operative rate in children of less than 6 months or
      older than 4 years and the rate of intestinal resection is higher than that in
      children's hospitals.

PMID- 21191780
TI  - Childhood craniopharyngioma in Macedonia: incidence and outcome after subtotal
      resection and cranial irradiation.
AB  - BACKGROUND: craniopharyngioma is a frequent tumor in children with challenging
      surgical, endocrine, and visual consequences. We evaluated our experience in
      treating craniopharyngioma and its incidence in Macedonia. METHODS: Thirteen
      children (9 male and 4 female) with craniopharyngioma (age 9.55 +/- 3.74 years;
      range 2.90-15.11) who had been treated between 1989 and 2008 in Macedonia were
      reviewed. RESULTS: initial signs were vision disturbances (10 children), seizures
      (1), growth retardation (13), and diabetes insipidus (DI) (2). All children were
      subjected to subtotal surgical removal. Cranial irradiation was performed in 12
      of the 13 children, and intracystic bleomycin was given to one child. The
      patients were followed up for 6-229 months (mean +/- SD: 107.00 +/- 74.04
      months). All children had multiple pituitary deficiencies after surgical removal
      of the tumor. Body mass index increased from 16.93 +/- 6.34 standard deviation
      scores (SDS) at diagnosis to 26.33 +/- 5.91 SDS (P>0.005) at the last follow-up.
      DI was permanent in 9 of the 13 children, and multiple pituitary deficiencies
      were seen in all children. Treatment with growth hormone resulted in
      normalization of adult height from -1.27 +/- 1.52 SDS at the start of the
      treatment to -0.13 +/- 1.39 SDS at the last followup. The final height was not
      significantly lower than the genetic target height (P>0.005). The permanent
      deficit was visual impairment: blindness in one or both eyes in 4 children,
      bitemporal hemianopsia in 4, and other defects in 2. Recurrence of the disease
      was ruled out in one child after 31 months. No mortality was observed in the
      observation period of 104.92 +/- 76.11 months. CONCLUSIONS: the overall incidence
      of craniopharyngioma in the period of 1989-2008 in Macedonia was 1.43 per 1 000
      000 person-years. Subtotal resection and systematic irradiation showed good life
      quality of survivors.

PMID- 21191781
TI  - Clinical outcome of nutrition-oriented intervention for primary intestinal
      lymphangiectasia.
AB  - BACKGROUND: primary intestinal lymphangiectasia (PIL) is a rare digestive disease
      and few studies have focused on the therapeutic effect in PIL patients. This
      study was undertaken to evaluate nutrition-oriented intervention in children with
      PIL. METHODS: four children with PIL were studied. Their medical records were
      reviewed. Anthropometric measurements and blood tests were performed during a 8
      18 month follow-up. RESULTS: during hospitalization, the 4 patients were
      subjected to diet intervention. Parenteral nutrition (PN) support was also given
      to 3 of them. Clinical symptoms and laboratory parameters of the patients were
      significantly improved at discharge. After discharge, the patients continued diet
      control, 2 of whom received intermittent PN support. The mean follow-up duration
      of the 4 patients was 13 months (range, 8-18 months) and they all kept in a
      stable condition without symptoms relapse. Weight, height and body mass index for
      age were normal during the follow-up, while total protein, albumin and
      immunoglobulin concentrations were still slightly below normal level.
      CONCLUSIONS: nutrition therapy is effective as a valid and safe therapeutic
      management for PIL patients. No growth retardation was observed in the 4 children
      after the therapy, but they are still at risk of nutrient malabsorption.
      Therefore, they need long-term, regular monitoring and intensive nutritional
      care.

PMID- 21191782
TI  - Massive bleeding after rectal suction biopsy: uncommon and unexpected delayed
      onset.
AB  - BACKGROUND: rectal suction biopsy is a safe and painless procedure commonly
      performed in pediatric surgical practice for the diagnosis of intestinal
      dysganglionosis. METHODS: we report a 3.5-year-old boy who experienced massive
      delayed bleeding after a rectal suction biopsy. Detailed information regarding
      clinical features, onset, management, and outcome are provided. RESULTS: acute
      onset of massive bleeding occurred 4 days after a rectal suction biopsy was
      performed to rule out possible intestinal dysganglionosis. The complication was
      managed conservatively, but blood transfusion and hospitalization were required.
      No predisposing abnormalities were detected. CONCLUSIONS: massive bleeding after
      rectal suction biopsy is a well-known life-threatening complication. Nonetheless,
      such a delayed bleeding (up to 4 days after a rectal suction biopsy) has never
      been reported before. Parents should be made aware of this possibility and
      surgeons should be aware of this complication which can be scarcely predicted
      based on patient's and familial history.

PMID- 21191783
TI  - Captopril induced reversible acute renal failure in a premature neonate with
      double outlet right ventricle and congestive heart failure.
AB  - BACKGROUND: captopril is well tolerated in most patients. There is no report of
      acute deterioration in renal function after administration of captopril in
      neonates with congestive heart failure secondary to congenital heart defects with
      large left-to-right shunts. METHODS: we report a premature neonate with double
      outlet right ventricle and congestive heart failure who developed acute renal
      failure after administration of captopril at a low dose of 0.1 mg/kg per 8 hours.
      RESULTS: on the third day after captopril therapy, the levels of serum creatinine
      and blood urea nitrogen increased to 2.6 mg/dl and 73 mg/dl respectively, and
      hyperkalemia appeared. Captopril was discontinued immediately. On the fourth day,
      the infant developed oliguria which persisted for 24 hours and resolved on the
      fifth day when the serum potassium normalized to 4.5 mmol/L. The level of serum
      creatinine peaked at 3.9 mg/dL on the sixth day and gradually decreased to normal
      on the ninth day after administration of captopril. The captopril-induced acute
      renal failure resolved completely after cessation of the drug. CONCLUSIONS:
      attention should be given to captopril therapy in premature neonates with
      congestive heart failure secondary to congenital heart disease with large left-to
      right shunts. Routine hemodynamic examination and biochemical monitoring are
      suggested before and during captopril therapy.

PMID- 21191785
TI  - Festschrift in the honor of Stephen H. White's 70th Birthday.
AB  - The Symposium 'Frontiers in membrane and membrane protein biophysics: experiments
      and theory', held this year at the University of California, Irvine (August 19
      20), celebrated the 70th Birthday of Stephen H. White by bringing together
      distinguished experimentalists and theoreticians to discuss the state of the art
      and future challenges in the field of membrane and membrane protein biophysics.
      The meeting and this special issue highlight the highly interdisciplinary nature
      of membrane and membrane protein biophysics, and the tremendous contributions
      that S. H. White and his lab have brought to the field.

PMID- 21191784
TI  - Endothelin receptor A-specific stimulation of glomerular inflammation and injury
      in a streptozotocin-induced rat model of diabetes.
AB  - AIMS/HYPOTHESIS: Activation of endothelin receptor-A (ET(A)) increases glomerular
      permeability to albumin (P(alb)) and elevates pro-inflammatory markers in
      hyperglycaemic rats. METHODS: Male Sprague-Dawley rats were given streptozotocin
      (n = 32) or saline (sham; n = 32). Half of the animals in each group received the
      ET(A)-selective antagonist, ABT-627 (atrasentan; orally), beginning immediately
      after hyperglycaemia was confirmed. Glomeruli were isolated by sieving techniques
      and P(alb) determined from the change in glomerular volume induced by oncotic
      gradients of albumin. Glomerular nephrin levels were assessed by
      immunofluorescence, whereas urinary nephrin was measured by immunoassay. RESULTS:
      At 3 and 6 weeks after streptozotocin injection, proteinuria was significantly
      increased compared with sham controls and significantly reduced by ABT-627
      treatment. P(alb) was also increased at 3 and 6 weeks post-streptozotocin. ABT
      627 had no effect on P(alb) or protein excretion in sham control rats. In
      glomeruli isolated from hyperglycaemic rats, incubation with BQ-123, a selective
      ET(A) antagonist, reduced P(alb), whereas BQ-788, a selective endothelin receptor
      B antagonist had no effect (n = 6 rats per group, 5-8 glomeruli per rat).
      Glomerular and plasma content of soluble intercellular adhesion molecule-1 and
      monocyte chemoattractant protein-1 were significantly increased 6 weeks after
      streptozotocin (ELISA). ABT-627 attenuated these increases. After 6 weeks of
      hyperglycaemia, glomerular nephrin content was decreased with a concurrent
      increase in urinary nephrin excretion. ABT-627 prevented glomerular nephrin loss
      in hyperglycaemic rats (n = 5-8 rats per group; eight groups).
      CONCLUSIONS/INTERPRETATION: These observations support the hypothesis that
      endothelin-1, via the ET(A) receptor, directly increases P(alb), possibly via
      nephrin loss, as well as early inflammation in the hyperglycaemic rat.

PMID- 21191786
TI  - Upgrading of straw hydrolysate for production of hydrogen and phenols in a
      microbial electrolysis cell (MEC).
AB  - In a microbial electrolysis cell (MEC), hydrolysate produced by hydrothermal
      treatment of wheat straw was used for hydrogen production during selective
      recovery of phenols. The average H2 production rate was 0.61 m3 H2/m3 MEC.day and
      equivalent to a rate of 0.40 kg COD/m3 MEC.day. The microbial community in the
      anode biofilm was adapted by establishment of xylose-degrading bacteria of the
      Bacteriodetes phylum (16%) and Geobacter sulfurreducens (49%). During the
      process, 61% of the chemical oxygen demand was removed as hydrogen at 64% yield.
      The total energy production yield was 78% considering the energy content in the
      consumed compounds and the cell voltage of 0.7 V. The highest hydrogen production
      was equivalent to 0.8 kg COD/m3 MEC.day and was obtained at pH 7-8 and 25 degrees
      C. Accumulation of 53% w/v phenolic compounds in the liquor was obtained by
      stepwise addition of the hydrolysate during simultaneous production of hydrogen
      from consumption of 95% for the hemicellulose and 100% of the fatty acids. Final
      calculations showed that hydrolysate produced from 1 kg wheat straw was upgraded
      by means of the MEC to 22 g hydrogen (266 L), 8 g xylan, and 9 g polyphenolics
      for potential utilization in biobased materials.

PMID- 21191787
TI  - The sense strand pre-cleaved RNA duplex mediates an efficient RNA interference
      with less off-target and immune response effects.
AB  - RNA interference is an appealing and promising therapeutic approach in cancer and
      other diseases. Designing novel strategies aiming to increase the efficiency,
      duration, and reduce the off-target silencing by sense strand is of great
      significance for its future application clinically. Here, we report that RNA
      duplex with the sense strand pre-cleaved at the base between base 10 and 11
      relative to the 5' end of the antisense strand induced a target-specific RNA
      silencing effectively. Furthermore, different from the canonical RNA duplex, this
      novel RNA duplex rarely inhibits the luciferase activity in the reporter, bearing
      the target sequence corresponding to the sense strand, suggesting a less off
      target effects of this novel strategy. Furthermore, the immune response of the
      novel RNA duplex induced a much milder immune response as seen from the NFkappaB
      activity. In addition, our newly designed RNA duplex should be easier for
      preservation than the asymmetric RNA duplex. Our results establish a novel method
      to design a new class of RNA duplex for improved RNA interference.

PMID- 21191788
TI  - Acidithiobacillus thiooxidans secretome containing a newly described lipoprotein
      Licanantase enhances chalcopyrite bioleaching rate.
AB  - The nature of the mineral-bacteria interphase where electron and mass transfer
      processes occur is a key element of the bioleaching processes of sulfide
      minerals. This interphase is composed of proteins, metabolites, and other
      compounds embedded in extracellular polymeric substances mainly consisting of
      sugars and lipids (Gehrke et al., Appl Environ Microbiol 64(7):2743-2747, 1998).
      On this respect, despite Acidithiobacilli-a ubiquitous bacterial genera in
      bioleaching processes (Rawlings, Microb Cell Fact 4(1):13, 2005)-has long been
      recognized as secreting bacteria (Jones and Starkey, J Bacteriol 82:788-789,
      1961; Schaeffer and Umbreit, J Bacteriol 85:492-493, 1963), few studies have been
      carried out in order to clarify the nature and the role of the secreted protein
      component: the secretome. This work characterizes for the first time the sulfur
      (meta)secretome of Acidithiobacillus thiooxidans strain DSM 17318 in pure and
      mixed cultures with Acidithiobacillus ferrooxidans DSM 16786, identifying the
      major component of these secreted fractions as a single lipoprotein named here as
      Licanantase. Bioleaching assays with the addition of Licanantase-enriched
      concentrated secretome fractions show that this newly found lipoprotein as an
      active protein additive exerts an increasing effect on chalcopyrite bioleaching
      rate.

PMID- 21191789
TI  - Lead induces oxidative stress and phenotypic markers of apoptosis in
      Saccharomyces cerevisiae.
AB  - In the present work, the mode of cell death induced by Pb in Saccharomyces
      cerevisiae was studied. Yeast cells Pb-exposed, up to 6 h, loss progressively the
      capacity to proliferate and maintained the membrane integrity evaluated by the
      fluorescent probes bis(1,3-dibutylbarbituric acid trimethine oxonol) and
      propidium iodide. Pb-induced death is an active process, requiring the
      participation of cellular metabolism, since the simultaneous addition of
      cycloheximide attenuated the loss of cell proliferation capacity. Cells exposed
      to Pb accumulated intracellularly reactive oxygen species (ROS), evaluated by
      2',7'-dichlorodihydrofluorescein diacetate. The addition of ascorbic acid (a ROS
      scavenger) strongly reduced the oxidative stress and impaired the loss of
      proliferation capacity in Pb-treated cells. Pb-exposed cells displayed nuclear
      morphological alterations, like chromatin fragmentation, as revealed by
      diaminophenylindole staining. Together, the data obtained indicate that yeast
      cells exposition to 1 mmol/l Pb results in severe oxidative stress which can be
      the trigger of programmed cell death by apoptosis.

PMID- 21191790
TI  - Research gaps related to forest management and stream sediment in the United
      States.
AB  - Water quality from forested landscapes tends to be very high but can deteriorate
      during and after silvicultural activities. Practices such as forest harvesting,
      site preparation, road construction/use, and stream crossings have been shown to
      contribute sediment, nutrients, and other pollutants to adjacent streams.
      Although advances in forest management accompanied with Best Management Practices
      (BMPs) have been very effective at reducing water quality impacts from forest
      operations, projected increases in demand for forest products may result in
      unintended environmental degradation. Through a review of the pertinent
      literature, we identified several research gaps related to water yield, aquatic
      habitat, sediment source and delivery, and BMP effectiveness that should be
      addressed for streams in the United States to better understand and address the
      environmental ramifications of current and future levels of timber production. We
      explored the current understanding of these topics based on relevant literature
      and the possible implications of increased demand for forest products in the
      United States.

PMID- 21191791
TI  - Cocoa intensification scenarios and their predicted impact on CO2 emissions,
      biodiversity conservation, and rural livelihoods in the Guinea rain forest of
      West Africa.
AB  - The Guinean rain forest (GRF) of West Africa, identified over 20 years ago as a
      global biodiversity hotspot, had reduced to 113,000 km2 at the start of the new
      millennium which was 18% of its original area. The principal driver of this
      environmental change has been the expansion of extensive smallholder agriculture.
      From 1988 to 2007, the area harvested in the GRF by smallholders of cocoa,
      cassava, and oil palm increased by 68,000 km2. Field results suggest a high
      potential for significantly increasing crop yields through increased application
      of seed-fertilizer technologies. Analyzing land-use change scenarios, it was
      estimated that had intensified cocoa technology, already developed in the 1960s,
      been pursued in Cote d'Ivoire, Ghana, Nigeria and Cameroon that over 21,000 km2
      of deforestation and forest degradation could have been avoided along with the
      emission of nearly 1.4 billion t of CO2. Addressing the low productivity of
      agriculture in the GRF should be one of the principal objectives of REDD climate
      mitigation programs.

PMID- 21191792
TI  - A review of the relative merits of conserving, using, or draining papyrus swamps.
AB  - Wetlands are a vital resource, particularly in Africa where livelihoods are
      closely linked to natural capital. In recent years, extensive drainage has
      occurred to make way for agriculture. To gain insight into whether drainage is
      justified, we review the value of African wetlands dominated by Cyperus papyrus
      in relation to use, conservation and conversion. Evidence suggests that the value
      derived from low-intensity, multifunctional wetland use far exceeds the value
      derived from swamp reclamation and generally exceeds that of conservation. At a
      local level, the main driver of wetland misuse appear to be a breakdown in
      collaborative management regimes and the main constraint on wetland use, the
      value of labor and selling-times. Local drivers are linked to regional factors
      such as the lack of coordinated wetland policies and difficulties in ensuring
      that legislation is absorbed by all sectors of society. We highlight
      opportunities for ensuring more effective collaborative management and
      legislation communication, which capitalize on existing governance structures. In
      contrast to predictions by Hardin's Tragedy of the Commons model, we argue that
      effective wetland management is best achieved by preventing privatization and
      promoting common property management regimes. We also argue that poverty and
      income inequity are more important drivers of unsustainable resource use than
      environmental managers commonly acknowledge.

PMID- 21191793
TI  - Infection by H1N1 flu virus revealing T-cell acute lymphoid leukaemia: about two
      cases.

PMID- 21191794
TI  - Assessment of breast cancer tumour size using six different methods.
AB  - OBJECTIVES: Tumour size estimates using mammography (MG), conventional ultrasound
      (US), compound imaging (CI) and real-time elastography (RTE) were compared with
      histopathological specimen sizes. METHODS: The largest diameters of 97 malignant
      breast lesions were measured. Two US and CI measurements were made: US1/CI1
      (hypoechoic nucleus only) and US2/CI2 (hypoechoic nucleus plus hyperechoic halo).
      Measurements were compared with histopathological tumour sizes using linear
      regression and Bland-Altman plots. RESULTS: Size prediction was best with
      ultrasound (US/CI/RTE: R (2) 0.31-0.36); mammography was poorer (R(2) = 0.19).
      The most accurate method was US2, while US1 and CI1 were poorest. Bland-Altman
      plots showed better size estimation with US2, CI2 and RTE, with low variation,
      while mammography showed greatest variability. Smaller tumours were better
      assessed than larger ones. CI2 and US2 performed best for ductal tumours and RTE
      for lobular cancers. Tumour size prediction accuracy did not correlate
      significantly with breast density, but on MG tumours were more difficult to
      detect in high-density tissue. CONCLUSIONS: The size of ductal tumours is best
      predicted with US2 and CI2, while for lobular cancers RTE is best. Hyperechoic
      tumour surroundings should be included in US and CI measurements and RTE used as
      an additional technique in the clinical staging process.

PMID- 21191795
TI  - Angiotensin II signaling up-regulates the immediate early transcription factor
      ATF3 in the left but not the right atrium.
AB  - The atria respond to various pathological stimuli including pressure and volume
      overload with remodeling and dilatation. Dilatation of the left atrium is
      associated with atrial fibrillation. The mechanisms involved in chamber-specific
      hypertrophy are largely unknown. Angiotensin II is hypothesized to take part in
      mediating this response. ATF3 is an immediate early gene found at the receiving
      end of multiple stress and growth stimuli. Here we characterize ATF3 as a direct
      target gene for angiotensin II. ATF3 expression is regulated by angiotensin
      receptor-mediated signaling in vivo and in vitro at the transcriptional level.
      ATF3 induction is mediated by cooperation between both the AT(1A) and AT2
      receptor subtypes. While AT2R blocker (PD123319) efficiently blocks ATF3
      induction in response to angiotensin II injection, it results in an increase in
      blood pressure indicating that the effect of angiotensin II on ATF3 is
      independent of its effect on blood pressure. In contrast to adrenergic
      stimulation that induces ATF3 in all heart chambers, ATF3 induction in response
      to angiotensin II occurs primarily in the left chambers. We hypothesize that the
      activation of differential signaling pathways accounts for the chamber-specific
      induction of ATF3 expression in response to angiotensin II stimulation.
      Angiotensin II injection rapidly activates the EGFR-dependent pathways including
      ERK and PI3K-AKT in the left but not the right atrium. EGF receptor inhibitor
      (Gefitinib/Iressa) as well as the AKT inhibitor (Triciribine) significantly
      abrogates ATF3 induction by angiotensin II in the left chambers. Collectively,
      our data strongly place ATF3 as a unique nuclear protein target in response to
      angiotensin II stimulation in the atria. The spatial expression of ATF3 may add
      to the understanding of the signaling pathways involved in cardiac response to
      neuro-hormonal stimulation, and in particular to the understanding of left atrial
      generated pathology such as atrial fibrillation.

PMID- 21191796
TI  - Fucoidan suppresses IgE production in peripheral blood mononuclear cells from
      patients with atopic dermatitis.
AB  - We previously reported that fucoidan, a dietary fiber purified from seaweed,
      inhibited IgE production in B cells from mice spleen in vitro and ovalbumin
      sensitized mice in vivo. In this study, we examined the effect of fucoidan on IgE
      production in human peripheral blood mononuclear cells (PBMC) in vitro. PBMC,
      obtained from healthy donors or patients with atopic dermatitis (AD) with high
      levels of serum IgE, were cultured with IL-4 and anti-CD40 antibody in the
      presence or absence of fucoidan. Fucoidan significantly reduced IgE production in
      PBMC without affecting cell proliferation and IFN-gamma production. Fucoidan also
      inhibited immunoglobulin germline transcripts of B cells in PBMC, and decreased
      the number of IgE-secreting cells. The inhibitory effects of fucoidan were
      similarly observed for both PBMC from patients with AD and those with healthy
      donors. Our findings indicate that fucoidan suppresses IgE induction by
      inhibiting immunoglobulin class-switching to IgE in human B cells, even after the
      onset of AD.

PMID- 21191797
TI  - Compact genomes and complex evolution in the genus Brachypodium.
AB  - The temperate annual grass Brachypodium distachyon is a diploid species with a
      chromosome base number of 5. It is strikingly different from other Eurasian
      species of the genus, which are perennial and often polyploid, with the diploids
      typically having base numbers of 8 or 9. Previously, phylogenies indicated that
      B. distachyon split from the other species early in the evolution of the genus,
      while its genome sequence revealed that extensive synteny on a chromosomal scale
      had been maintained with rice, a tropical grass with a base number of 12. Here we
      show evidence that B. distachyon may have a homoploid origin, involving ancestral
      interspecific hybridisation, although it does not appear to be a component of any
      of the perennial Eurasian allopolyploids. Using a cytogenetic approach, we show
      that dysploidy in Brachypodium has not followed a simple progression.

PMID- 21191798
TI  - Effects of whole-body heat acclimation on cell injury and cytokine responses in
      peripheral blood mononuclear cells.
AB  - To test the hypothesis that whole-body heat acclimation (HA) would increase
      peripheral blood mononuclear cells' (PBMC) tolerance to heat shock (HS) and/or
      alter the release of cytokines (IL-1beta, IL-6, IL-10 and TNF-alpha) to bacterial
      lipopolysaccharide (LPS), we heat acclimated nine subjects by exercising them for
      100 min in a hot environment for 10 days. The subjects' PBMC were separated and
      cultured on days 1 and 10 of HA pre- and post-exercise. Pre-exercise PBMC were
      allocated to three treatments: control (PRE, 37 degrees C), HS (42.5 degrees C
      for 2 h), or LPS (1 ng mL(-1) for 24 h). Post-exercise samples were incubated at
      37 degrees C. PBMC lactate dehydrogenase release increased (p < 0.05) after HS
      but it was not different (p > 0.05) between days 1 and 10 (0.100 +/- 0.012 and
      0.102 +/- 0.16 abs., respectively). LPS treatment induced an increased (p < 0.05)
      release of cytokines but HA did not alter this response (p > 0.05). Pre-exercise
      intracellular heat shock protein 72 (Hsp72) was higher (p < 0.05) on day 10
      compared to day 1 of HA (13 +/- 5 and 8 +/- 5 ng mL(-1), respectively). HS
      treatment caused a greater increase (p < 0.05) in Hsp72 than the exercise
      sessions on HA days 1 and 10. In addition, after HA, the Hsp72 response to HS was
      reduced (day 1, 129 +/- 46; day 10, 80 +/- 32 ng mL(-1), p < 0.05). In
      conclusion, HA increases PBMC Hsp72 but it does not reduce cellular damage to HS
      or alter cytokine response to LPS. We speculate that the stress applied during HA
      is not sufficient to modify the PBMC response.

PMID- 21191799
TI  - Resource manipulation effects on net primary production, biomass allocation and
      rain-use efficiency of two semiarid grassland sites in Inner Mongolia, China.
AB  - Productivity of semiarid grasslands is affected by soil water and nutrient
      availability, with water controlling net primary production under dry conditions
      and soil nutrients constraining biomass production under wet conditions. In order
      to investigate limitations on plants by the response of root-shoot biomass
      allocation to water and nitrogen (N) availability, a field experiment, on
      restoration plots with rainfed, unfertilized control plots, fertilized plots
      receiving N (25 kg urea-N ha(-1)) and water (irrigation simulating a wet season),
      was conducted at two sites with different grazing histories: moderate (MG) and
      heavy (HG) grazing. Irrigation and N addition had no effect on belowground
      biomass. Irrigation increased aboveground (ANPP) and belowground net primary
      production (BNPP) and rain-use efficiency based on ANPP (RUE(ANPP)), whereas N
      addition on rainfed plots had no effect on any of the measured parameters. N
      fertilizer application on irrigated plots increased ANPP and RUE(ANPP) and
      reduced the root fraction (RF: root dry matter/total dry matter), resulting in
      smaller N effects on total net primary production (NPP) and rain-use efficiency
      based on NPP. This suggests that BNPP should be included in evaluating ecosystem
      responses to resource availability from the whole-plant perspective. N effects on
      all measured parameters were similar on both sites. However, site HG responded to
      irrigation with higher ANPP and a lower RF when compared to site MG, indicating
      that species composition had a pronounced effect on carbon allocation pattern due
      to below- and aboveground niche complementarity.

PMID- 21191800
TI  - Formal adult infectious disease specialist consultations in the outpatient
      setting at a comprehensive cancer center (1998-2008): diverse and impactful.
AB  - PURPOSE: The literature on the impact of infectious disease (ID) consulations in
      the outpatient treatment of cancer is scarce. METHODS: The medical records of
      consecutive adult patients with cancer formally evaluated by two board-certified
      ID specialists in an outpatient setting at our institution over a 10-year period
      (1998-2008) were reviewed retrospectively. The patients' demographics, referring
      departments, purposes for consultation, ID specialist recommendations, and
      overall impact of consultations on outcome were analyzed. RESULTS: We identified
      598 patients who underwent ID specialist consultations. Most of them had solid
      tumors (53%), predominantly breast cancer, whereas non-Hodgkin's lymphoma was the
      most common hematologic malignancy. Almost half of the patients (45%) had active
      malignancies, but few of them were severely neutropenic (8%) or had been
      receiving high doses of corticosteroids (17%). The most frequent requests for
      consultation were culture or serologic test (15%), and treatment of cellulitis
      and/or surgical wound infections (14%). Of 337 isolated pathogens, the most
      prevalent were methicillin-resistant Staphylococcus aureus (13%) and Pseudomonas
      aeruginosa (8%), as well as atypical mycobacteria (16%) and Aspergillus species
      (11%). ID specialists provided alternative diagnoses in 53% of the cases,
      including identification of a different infection (46%), a noninfectious etiology
      (29%), colonization (16%), and drug-related toxic effects (9%). Overall, we
      deemed the contribution of the ID specialist to be significant in 62% of the
      consultations. CONCLUSIONS: ID specialists contribute significantly to the
      outpatient care of individuals with cancer.

PMID- 21191801
TI  - Long-term quality of life in Australian women previously diagnosed with
      gynaecologic cancer.
AB  - PURPOSE: The purpose of this study is to investigate challenges to quality of
      life (QOL) among women previously diagnosed with gynaecologic cancer accessing a
      metropolitan Australian oncology service. Indices of QOL investigated were
      anxiety, depression, sexual morbidity, body image and supportive care needs.
      Findings are to inform service planning and research priorities. METHODS: This
      study is a cross-sectional analysis of 176 women diagnosed with gynaecologic
      cancer from 1997 to 2006. Data were collected from medical records and via self
      report questionnaire comprising validated measures of QOL indices. RESULTS:
      Respondents have cancers of the endometrium (n = 56, 32%), ovary (n = 71, 40%),
      cervix (n = 27, 15%) and other less common types (n = 22, 13%). Mean (SD) age and
      time since diagnosis were 58.6 (13.2) and 4.7 (2.9) years, respectively. Using
      cut-offs of >= 8 and >= 11 on the Hospital Anxiety and Depression Scale, 55 (31%)
      and 27 (15%) women reported anxiety and 28 (16%) and 10 (6%) women reported
      depression, respectively. On average, 5.26 unmet needs were reported. Concerns
      about recurrence were the most common unmet need (30%). Two thirds had not been
      sexually active in the preceding month. Most (87%) were not worried about their
      sex life or lack thereof. Mean (SD) score on the Body Image Scale was 7.21
      (7.37). Tumour groups did not differ on any outcomes. CONCLUSIONS: Despite
      limitations, these data shed light on challenges to QOL of a heterogeneous group
      of gynaecologic cancer survivors. Sexual and psychological morbidity outcomes
      compare favourably with the literature while body image disturbance may present a
      useful target for clinical intervention.

PMID- 21191802
TI  - Evidence for the genesis of WHO grade II glioma in an asymptomatic young adult
      using repeated MRIs.
AB  - As the natural course of WHO grade II glioma (G2G) during their initial silent
      period is unknown, the G2G genesis and their "date of birth" are a matter of
      debate. Here, a left temporo-insular G2G was discovered incidentally in a 31-year
      old man in 2009 (MRI performed for a Chiari malformation). The mean tumor
      diameter increased from 29 (April 2009) to 31 mm (October 2009) before surgery.
      Since we recently demonstrated that the growth rate is constant during the
      initial silent period in G2G, the extrapolation backward in time leads to date
      the glioma birth in 2002. This observation is in agreement with an MRI performed
      in 1997, where no signal abnormality was detected. To our knowledge, this is the
      first report demonstrating that the tumorigenesis of a G2G occurs during the
      young adult period. In addition, estimation of the date of birth may serve as a
      reproducible "starting point" when analyzing survivals in series of G2G.

PMID- 21191803
TI  - Using increment of diversity to predict mitochondrial proteins of malaria
      parasite: integrating pseudo-amino acid composition and structural alphabet.
AB  - Due to the complexity of Plasmodium falciparum (PF) genome, predicting
      mitochondrial proteins of PF is more difficult than other species. In this study,
      using the n-peptide composition of reduced amino acid alphabet (RAAA) obtained
      from structural alphabet named Protein Blocks as feature parameter, the increment
      of diversity (ID) is firstly developed to predict mitochondrial proteins. By
      choosing the 1-peptide compositions on the N-terminal regions with 20 residues as
      the only input vector, the prediction performance achieves 86.86% accuracy with
      0.69 Mathew's correlation coefficient (MCC) by the jackknife test. Moreover, by
      combining with the hydropathy distribution along protein sequence and several
      reduced amino acid alphabets, we achieved maximum MCC 0.82 with accuracy 92% in
      the jackknife test by using the developed ID model. When evaluating on an
      independent dataset our method performs better than existing methods. The results
      indicate that the ID is a simple and efficient prediction method for
      mitochondrial proteins of malaria parasite.

PMID- 21191804
TI  - Hypocholesterolemia is associated negatively with hemolysate lipid peroxidation
      in sickle cell anemia patients.
AB  - The oxidative stress levels in plasma and hemolysate and cholesterol levels in
      plasma of sickle cell anemia patients, carriers and controls were evaluated. A
      total of 40 cases-17 patients, 13 carriers and 10 controls-were involved in the
      study. Plasma and hemolysate malondialdehyde (MDA) were detected via
      thiobarbituric acid reaction with a fluorimetric detector by high-performance
      liquid chromatography system. Plasma cholesterol was determined by enzymatic
      colorimetric method. Mean MDA levels of SCA patients were higher than those of
      the carriers' and healthy children's both in plasma and in hemolysate (P <
      0.005). The mean plasma and hemolysate MDA levels were 25.3 +/- 1.6 nmol/l and
      86.7 +/- 19.3 nmol/l in patients, 19.1 +/- 0.8 nmol/l and 54.1 +/- 10.8 nmol/l in
      carriers and 19.6 +/- 0.8 nmol/l and 56.8 +/- 9.3 nmol/l in healthy children.
      Mean plasma total cholesterol levels were 92.1 +/- 19.1 mg/dl in patients, 116.2
      +/- 23.3 mg/dl in carriers and 126.6 +/- 16.4 mg/dl in controls (P < 0.005).
      There was a significant negative correlation of -0.520 between hemolysate MDA and
      plasma cholesterol levels in patients (P < 0.05). The degree of correlation
      increased up to -0.782 (P = 0.008) in the patients with HbSS phenotype. This
      negative correlation between MDA and cholesterol may imply a potential
      association between oxidative stress and hypocholesterolemia in sickle cell
      anemia.

PMID- 21191805
TI  - RDC derived protein backbone resonance assignment using fragment assembly.
AB  - Experimental residual dipolar couplings (RDCs) in combination with structural
      models have the potential for accelerating the protein backbone resonance
      assignment process because RDCs can be measured accurately and interpreted
      quantitatively. However, this application has been limited due to the need for
      very high-resolution structural templates. Here, we introduce a new approach to
      resonance assignment based on optimal agreement between the experimental and
      calculated RDCs from a structural template that contains all assignable residues.
      To overcome the inherent computational complexity of such a global search, we
      have adopted an efficient two-stage search algorithm and included connectivity
      data from conventional assignment experiments. In the first stage, a list of
      strings of resonances (CA-links) is generated via exhaustive searches for short
      segments of sequentially connected residues in a protein (local templates), and
      then ranked by the agreement of the experimental (13)C(alpha) chemical shifts and
      (15)N-(1)H RDCs to the predicted values for each local template. In the second
      stage, the top CA-links for different local templates in stage I are
      combinatorially connected to produce CA-links for all assignable residues. The
      resulting CA-links are ranked for resonance assignment according to their
      measured RDCs and predicted values from a tertiary structure. Since the final RDC
      ranking of CA-links includes all assignable residues and the assignment is
      derived from a "global minimum", our approach is far less reliant on the quality
      of experimental data and structural templates. The present approach is validated
      with the assignments of several proteins, including a 42 kDa maltose binding
      protein (MBP) using RDCs and structural templates of varying quality. Since
      backbone resonance assignment is an essential first step for most of biomolecular
      NMR applications and is often a bottleneck for large systems, we expect that this
      new approach will improve the efficiency of the assignment process for small and
      medium size proteins and will extend the size limits assignable by current
      methods for proteins with structural models.

PMID- 21191806
TI  - Behavioral responses of the leafhopper, Cicadulina storeyi China, a major vector
      of maize streak virus, to volatile cues from intact and leafhopper-damaged maize.
AB  - The chemical ecology of the leafhopper, Cicadulina storeyi China (Homoptera:
      Cicadellidae), an important vector of Maize Streak Virus (MSV), was studied with
      a view to developing novel leafhopper control strategies in sub-Saharan Africa.
      Choice tests using a Y-tube olfactometer revealed that odors from uninfested
      maize seedlings (Zea mays cv. Delprim) were significantly more attractive to C.
      storeyi than odors from C. storeyi-infested seedlings. Headspace samples of
      volatile organic compounds (VOCs) collected from 10 to 12 day-old uninfested
      seedlings were more attractive than those collected from infested seedlings.
      While VOCs collected from uninfested maize seedlings were attractive, VOCs
      collected from C. storeyi-infested seedlings were significantly repellent.
      Analysis of the collected VOCs by gas chromatography (GC) and coupled GC-mass
      spectrometry (GC-MS) led to the identification of myrcene, linalool, (E)-2-decen
      1-ol, and decanal from uninfested seedlings, and (Z)-3-hexenyl acetate, (E)-4,8
      dimethyl-1,3,7-nonatriene (DMNT), methyl salicylate, benzyl acetate, indole,
      geranyl acetate, (E)-caryophyllene, alpha-bergamotene, (E)-beta-farnesene, beta
      sesquiphellandrene, and (E,E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene (TMTT)
      from infested seedlings. Of these, methyl salicylate, (E)-caryophyllene, (E)-beta
      farnesene, and TMTT were identified previously as volatile semiochemicals
      involved in plant defense against other sucking insect pests. When tested
      individually for behavioral activity, all compounds were repellent for C.
      storeyi. Moreover, when these induced VOCs were added to the blend of VOCs from
      uninfested maize seedlings, a shift from attraction to repellency was observed.
      Addition of methyl salicylate, (E)-beta-farnesene, or TMTT resulted in a choice
      for the solvent control (i.e., repulsion), whereas addition of (E)-caryophyllene
      resulted in no reduction in host VOC attractiveness. These results show that VOCs
      induced in maize have the potential to be exploited in the control of
      viruliferous leafhoppers in sub-Saharan Africa.

PMID- 21191807
TI  - Changes of brain structure and function in ADHD children.
AB  - To explore the changes of brain structure and function in attention
      deficit/hyperactivity disorder (ADHD), fifteen ADHD patients (inattention
      subtype) and 15 normal control participants were recruited, the brain structure
      and function of these subjects were investigated by combining structural magnetic
      resonance imaging (MRI), diffusion tensor imaging and resting-state functional
      MRI. The results showed that ADHD patients had a significant decrease in the
      volume of the white matter (P = 0.04), and a trend toward decreased volume of
      brain structures except for the putamen and globus pallidus. The visualization of
      statistical difference maps of the cortical thickness showed that ADHD patients
      had focal thinning in bilateral frontal regions and the right cingulate cortex (P
      < 0.05 uncorrected, except for a cluster threshold of 10 voxels). Statistical
      analysis of the FA maps revealed that ADHD patients had significantly decreased
      FA in the forceps minor, the internal capsule, the corona radiata, the splenium
      of the corpus callosum, and the bilateral basal ganglia (P < 0.05 uncorrected as
      above). ADHD patients had significantly decreased functional connectivity in the
      anterior cingulate cortex, posterior cingulate cortex, lateral prefrontal cortex,
      left precuneus and thalamus, but increased functional connectivity in bilateral
      posterior medial frontal cortex in the default mode network (P < 0.05 uncorrected
      as above). Our results provide new insights into the changes of the brain
      structure and function in ADHD, which suggests that alterations in the brain
      structural and functional connectivity might implicate the pathophysiology of
      ADHD.

PMID- 21191808
TI  - Reduction of hepatocellular carcinoma in childhood after introduction of
      selective vaccination against hepatitis B virus for infants born to HBV carrier
      mothers.
AB  - OBJECTIVE: A nation-wide prevention program utilizing passive-active
      immunoprophylaxis for high-risk babies against maternal HBV transmission was
      introduced in Japan in January of 1986. The prevention program was expected to
      eradicate HBV-related hepatocellular carcinoma (HCC). The aim of this study was
      to evaluate the effect of this selective prevention program against maternal HBV
      transmission on the occurrence of HBV-related HCC. METHODS: We reviewed the
      annual reports from a nation-wide survey of childhood solid tumors that was
      reported in the Journal of the Japanese Society of Pediatric Surgeons during the
      28 years period from 1981 to 2008. The number of HCC cases were grouped for every
      5-year period with an additional period of the past 3 years and compared with
      those of hepatoblastoma. RESULTS: The reported number of children with
      hepatoblastoma in each period was constant during the 28 years study period. In
      contrast, both the number of patients with HBV-related HCC and the ratio of HBV
      related HCC to hepatoblastoma gradually decreased over the study period, with a
      significant drop in the last two periods ranging from 2001 to 2008 (p < 0.001).
      CONCLUSION: The prevention program against maternal HBV infection of infants born
      to HBV carrier mothers may have decreased the occurrence of HBV-related HCC in
      childhood.

PMID- 21191809
TI  - Influence of alginic acid and fucoidan on the immune responses of head kidney
      leukocytes in cod.
AB  - The present study investigated the immunomodulatory activities of alginic acid
      and fucoidan, both derived from brown seaweeds, on selected cellular immune
      responses and antibacterial activity of head kidney (HK) leukocytes of cod, Gadus
      morhua. Primary cultures of HK leukocytes were incubated with either 10 or 100
      MUg ml-1 of the substances and the effects on respiratory burst, cellular
      proliferation, acid and alkaline phosphatase activity and cellular
      myeloperoxidase were measured at 3- and 24-h post-incubation. The antibacterial
      activity of the supernatants collected from the cell cultures incubated with 100
      MUg ml-1 of the substances were tested against Vibrio anguillarum and Aeromonas
      salmonicida. Respiratory burst was significantly elevated in cells incubated with
      either alginic acid or fucoidan in a dose-dependent manner. Incubation with a
      higher dose of alginic acid and fucoidan resulted in lower cellular proliferation
      at 3- and 24-h, respectively. Both acid and alkaline phosphatase activities of HK
      leukocytes were not significantly modulated, except for a slight elevation of
      acid phosphatase in cells incubated with 100 MUg ml-1 of alginic acid for 24-h.
      Fucoidan, but not alginic acid significantly increased cellular myeloperoxidase
      activity at a concentration of 100 MUg ml-1. The growth of the bacteria in both
      the treated and control supernatants was significantly lower than what was
      observed in the bacterial culture medium. However, the supernatants from the
      treated cells had significantly higher bacterial growth compared with
      supernatants of the control cells. Taken together, these results showed that at
      the tested concentrations, both alginic acid and fucoidan are able to
      differentially stimulate some cellular immune responses of cod HK leukocytes in
      vitro and the respiratory burst activity was significantly stimulated by these
      brown algal derivatives. These substances could be tested as potential
      immunostimulants in future in vivo studies.

PMID- 21191810
TI  - Involvement of IGF binding protein 5 in prostaglandin E(2)-induced cellular
      senescence in human fibroblasts.
AB  - Inflammation is an underlying basis for the molecular alterations that link aging
      and age-related pathological processes. In a previous study, we found that
      secretory phospholipase A(2) (sPLA(2)) induced cellular senescence in human
      dermal fibroblasts (HDFs). To further investigate the association of inflammation
      with cellular senescence, the effects of PGE(2) on cellular senescence in HDFs
      were investigated, since PGE(2) is the most abundant prostanoid. PGE(2) treatment
      induces cellular senescence, as determined by a decrease in cell proliferation
      and an increase in senescence-associated beta-galactosidase staining. Notably,
      PGE(2) treatment increased the IGFBP5 protein level. While treatment with PGE(2)
      antagonists repressed PGE(2)-induced cellular senescence, increasing
      intracellular cAMP accelerated cellular senescence. Down-regulation of IGFBP5
      inhibited PGE(2)-induced cellular senescence. Taken together, these results
      suggest that PGE(2) may play an important role in controlling cellular senescence
      of HDFs through the regulation of IGFBP5 and therefore may contribute to
      inflammatory disorders associated with aging.

PMID- 21191812
TI  - ANK repeat-domain of SHN-1 Is indispensable for in vivo SHN-1 function in C.
      elegans.
AB  - Shank protein is one of the postsynaptic density (PSD) proteins which play a
      major role in proper localization of proteins at membranes. The shn-1, a homolog
      of Shank in Caenorhabditis elegans, is expressed in neurons, pharynx, intestine,
      vulva and sperm. We have previously reported a possible genetic interaction
      between Shank and IP3 receptor by examining shn-1 RNAi in IP3 receptor (itr-1)
      mutant background. In order to show the direct interaction of Shank and IP3
      receptor as well as to show the direct in vivo function of Shank, we have
      characterized two different mutant alleles of shn-1, which have different
      deletions in the different domains. shn-1 mutants were observed for Ca2+-related
      behavioral defects with itr-1 mutants. We found that only shn-1 mutant defective
      in ANK repeat-domain showed significant defects in defecation, pharyngeal pumping
      and fertility. In addition, we found that shn-1 regulates defecation, pharyngeal
      pumping and probably male fertility with itr-1. Thus, we suggest that Shank ANK
      repeat-domain along with PDZ may play a crucial role in regulating Ca2+-signaling
      with IP3 receptor.

PMID- 21191813
TI  - Analysis of gene expression profiles of liver stellate cells during liver
      regeneration in rats.
AB  - This study performed a large-scale, high-throughput analysis of transcriptional
      profiling of liver stellate cells (LSCs) at the cellular level to investigate
      changes in the biological activity of LSCs during rat liver regeneration (LR) and
      the relation of these changes to LR. First, a rat liver regeneration model was
      established by partial hepatectomy (PH). Stellate cells were isolated in high
      purity and yield from the regenerating rat liver by Percoll density gradient
      centrifugation and immunomagnetic bead sorting. The changes in gene expression of
      LSCs after PH were examined using a rat genome 230 2.0 array composed of 24622
      genes. The results indicated that 10241 of the 24622 genes investigated on the
      array were differentially expressed in LSCs. Of the 10241 genes, 1563 known genes
      were related to LR, which were grouped into three major gene expression clusters
      according to three-fold cut-off threshold: the upregulated gene cluster, the down
      regulated gene cluster, and the cluster composed of genes showing complex changes
      in expression. Additionally, the genes were grouped into those involved in
      transcription regulation, signal transduction, transport, cellular metabolism,
      inflammation and immunity by functional analysis. When gene expression profiles
      were combined with the results of gene functional analysis, most of the genes
      involved in cytokine secretion and retinol metabolism in LSCs were significantly
      enriched in the cluster characterized by decreased expression, whereas genes
      involved in lipid metabolism were mostly enriched in the cluster showing
      increased expression. Based on further analysis of genes expressed in a phase
      dependent manner during LR, it was suggested that lipid metabolism in LSCs was
      enhanced in the whole regeneration process, and that immune response and cytokine
      secretion were impaired during all three regenerative phases.

PMID- 21191814
TI  - Immunostimulating activity by polysaccharides isolated from fruiting body of
      Inonotus obliquus.
AB  - In this study, we investigated the immunostimulating activity of polysaccharides
      isolated from fruiting body of Inonotus obliquus (PFIO). Additionally, the
      signaling pathway of PFIO-mediated macrophage activation was investigated in
      RAW264.7 macrophage cells. We found that PFIO was capable of promoting NO/ROS
      production, TNF-alpha secretion and phagocytic uptake in macrophages, as well as
      cell proliferation, comitogenic effect and IFN-gamma/IL-4 secretion in mouse
      splenocytes. PFIO was able to induce the phosphorylation of three MAPKs as well
      as the nuclear translocation of NF-kappaB, resulting in activation of RAW264.7
      macrophages. PFIO also induced the inhibition of TNF-alpha secretion by anti-TLR2
      mAb, consequently, PFIO might be involved in TNF-alpha secretion via the TLR2
      receptor. In addition, our results showed that oral administration of PFIO
      suppressed in vivo growth of melanoma tumor in tumorbearing mice. In conclusion,
      our experiments presented that PFIO effectively promotes macrophage activation
      through the MAPK and NF-kappaB signaling pathways, suggesting that PFIO may
      potentially regulate the immune response.

PMID- 21191815
TI  - Regulation of sperm-specific proteins by IFE-1, a germline-specific homolog of
      eIF4E, in C. elegans.
AB  - ABSTEACT: IFE-1 is one of the five C. elegans homologs of eIF4E, which is the
      mRNA 5' cap-binding component of the translation initiation complex eIF4F.
      Depletion of IFE-1 causes defects in sperm, suggesting that IFE-1 regulates a
      subset of genes required for sperm functions. To further understand the molecular
      function of IFE-1, proteomic analysis was performed to search for sperm proteins
      that are downregulated in ife-1(ok1978); fem-3(q20) mutants relative to the fem
      3(q20) control. The fem-3(q20) mutant background was used because it only
      produces sperm at restrictive temperature. Total worm proteins were subjected to
      2D-DIGE, and differentially expressed protein spots were further identified by
      MALDI-TOF mass spectrometry. Among the identified proteins, GSP-3 and Major Sperm
      Proteins (MSPs) were found to be significantly down-regulated in the ife
      1(ok1978) mutant. Moreover, RNAi of gsp-3 caused an ife-1-like phenotype. These
      results suggest that IFE-1 is required for efficient expression of some sperm
      specific proteins, and the fertilization defect of ife-1 mutant is caused mainly
      by a reduced level of GSP-3.

PMID- 21191816
TI  - Epigenetic up-regulation of leukemia inhibitory factor (LIF) gene during the
      progression to breast cancer.
AB  - The interleukin 6 family of cytokines including leukemia inhibitory factor (LIF)
      regulates the progression of several types of cancer. However, although LIF
      overexpression during breast cancer progression was observed in our previous
      report, the molecular mechanisms responsible for this deregulation remain largely
      unknown. Here we show that LIF expression is epigenetically up-regulated via DNA
      demethylation and changes in histone methylation status within its promoter
      region in the isogenic MCF10 model. Bisulfite sequencing revealed the CpG pairs
      within the promoter region are hypermethylated in normal breast epithelial cells,
      but extensively demethylated as breast cancer progresses. In agreement with the
      DNA methylation pattern, our chromatin immunoprecipitation showed that inactive
      epigenetic marks such as MeCP2 occupancy and histone H3-Lys9-dimethylation
      significantly decreased during the progression to breast cancer but an active
      histone mark was increased in an inverse manner. Also, the occupancy of the
      transcription factor Sp1, which has higher affinity for hypomethylated CpGs,
      increased. RNAi-mediated knockdown of LIF expression resulted in a significant
      reduction of cell growth and colony formation in breast cancer cells, suggesting
      the potential role of LIF-LIF receptor axis in autocrine stimulation of cancer
      cells. Collectively, our data suggest that the epigenetic up-regulation of the
      LIF gene likely play an important role in the development of breast cancer.

PMID- 21191817
TI  - A critical time window for the survival of neural progenitor cells by HDAC
      inhibitors in the hippocampus.
AB  - Histone deacetylase inhibitors (HDACIs) that modulate gene expression by
      inhibiting HDAC enzymes may contribute to the survival of immature hippocampal
      neurons. However, it remains unknown how and when HDACIs regulate the survival of
      newly generated immature hippocampal neurons. In the present study, if the
      treatment of valproic acid (VPA) and sodium butyrate (SBt) in the specific time
      window during the development of newly generated n eurons r esulted in the i
      ncreased survival of bromodeoxyuridine (BrdU)(+) neurons in the dentate gyrus
      (DG) of hippocampus in mice was investigated. It was found that the number of
      BrdU(+) cells, the expressions of anti-apoptotic Bcl-2 family members and pCREB
      [D1] were increased by HDACIs when HDACIs were treated no later than 2-3 weeks
      after BrdU labeling. This suggests that epigenetic modification within a specific
      time window is critical for the survival of newborn hippocampal neurons by
      inhibiting the apoptotic pathway.

PMID- 21191818
TI  - Ginsenoside Rg3 enhances large conductance Ca2+-activated potassium channel
      currents: a role of Tyr360 residue.
AB  - Ginsenosides, active ingredients of Panax ginseng, are known to exhibit
      neuroprotective effects. Large-conductance Ca(2+)-activated K(+) (BK(Ca))
      channels are key modulators of cellular excitability of neurons and vascular
      smooth muscle cells. In the present study, we examined the effects of
      ginsenosides on rat brain BK(Ca) (rSlo) channel activity heterologously expressed
      in Xenopus oocytes to elucidate the molecular mechanisms how ginsenoside
      regulates the BK(Ca) channel activity. Ginsenoside Rg(3) (Rg(3)) enhanced outward
      BK(Ca) channel currents. The Rg(3)-enhancement of outward BK(Ca) channel currents
      was concentration-dependent, voltage-dependent, and reversible. The EC(50) was
      15.1 +/- 3.1 MUM. Rg(3) actions were not desensitized by repeated treatment.
      Tetraetylammonium (TEA), a K(+) channel blocker, inhibited BK(Ca) channel
      currents. We examined whether extracellular TEA treatment could alter the Rg(3)
      action and vice versa. TEA caused a rightward shift of the Rg(3) concentration
      response curve (i.e., much higher concentration of Rg(3) is required for the
      activation of BK(Ca) channel compared to the absence of TEA), while Rg(3) caused
      a rightward shift of the TEA concentration-response curve in wild-type channels.
      Mutation of the extracellular TEA binding site Y360 to Y360I caused a rightward
      shift of the TEA concentration-response curve and almost abolished both the Rg(3)
      action and Rg(3)-induced rightward shift of TEA concentration-response curve.
      These results indicate that Tyr360 residue of BK(Ca) channel plays an important
      role in the Rg(3)-enhancement of BK(Ca) channel currents.

PMID- 21191820
TI  - Dietary excess vanadium induces lesions and changes of cell cycle of spleen in
      broilers.
AB  - The purpose of this 42-day study was to investigate the effects of dietary excess
      vanadium on spleen growth and lesions by determining morphological changes and
      cell cycle of spleen. Four hundred twenty 1-day-old avian broilers were divided
      into six groups and fed on a corn-soybean basal diet as control diet or the same
      diet amended to contain 5, 15, 30, 45, 60 ppm of vanadium supplied as ammonium
      metavanadate. When compared with that of control group, the relative weight of
      spleen was significantly raised in 5- and 15-ppm groups, but depressed in 45- and
      60-ppm groups. The gross lesions of spleen showed obvious atrophy with decreased
      volume and pale color in 45- and 60-ppm groups. Histopathologically, lymphocytes
      in splenic corpuscle and periarterial lymphatic sheath were variously decreased
      in number in 30-, 45-, and 60-ppm groups. The percentage of static phase (G0/G1)
      was significantly decreased, and the percentage of synthesis period (S) phase and
      the proliferating index (PI) were significantly increased in 5- and 15-ppm
      groups. The percentage of G0/G1 phase was significantly increased, and the
      percentage of mitotic phase (G2+M), S phase, and PI significantly decreased in 45
      and 60-ppm groups. These results suggested that dietary excess vanadium (45 and
      60 ppm) could inhibit growth of spleen and induce lesions in spleen in chicken.

PMID- 21191819
TI  - The incremental value of self-reported mental health measures in predicting
      functional outcomes of veterans.
AB  - Research on patient-centered care supports use of patient/consumer self-report
      measures in monitoring health outcomes. This study examined the incremental value
      of self-report mental health measures relative to a clinician-rated measure in
      predicting functional outcomes among mental health service recipients.
      Participants (n = 446) completed the Behavior and Symptom Identification Scale,
      the Brief Symptom Inventory, and the Veterans/Rand Short Form-36 at enrollment in
      the study (T1) and 3 months later (T2). Global Assessment of Functioning (GAF)
      ratings, mental health service utilization, and psychiatric diagnoses were
      obtained from administrative data files. Controlling for demographic and clinical
      variables, results indicated that improvement based on the self-report measures
      significantly predicted one or more functional outcomes (i.e., decreased
      likelihood of post-enrollment psychiatric hospitalization and increased
      likelihood of paid employment), above and beyond the predictive value of the GAF.
      Inclusion of self-report measures may be a useful addition to performance
      measurement efforts.

PMID- 21191821
TI  - Modulation of exogenous glutathione in phytochelatins and photosynthetic
      performance against cd stress in the two rice genotypes differing in Cd
      tolerance.
AB  - Greenhouse hydroponic experiments were conducted using Cd-sensitive (Xiushui63)
      and tolerant (Bing97252) rice genotypes to evaluate genotypic differences in
      response of photosynthesis and phytochelatins to Cd toxicity in the presence of
      exogenous glutathione (GSH). Plant height, chlorophyll content, net
      photosynthetic rate (Pn), and biomass decreased in 5 and 50 MUM Cd treatments,
      and Cd-sensitive genotype showed more severe reduction than the tolerant one.
      Cadmium stress caused decrease in maximal photochemical efficiency of PSII
      (Fv/Fm) and effective PSII quantum yield [Y(II)] and increase in quantum yield of
      regulated energy dissipation [Y(NPQ)], with changes in Cd-sensitive genotype
      being more evident. Cadmium-induced phytochelatins (PCs), GSH, and cysteine
      accumulation was observed in roots of both genotypes, with markedly higher level
      in PCs and GSH on day 5 in Bing97252 compared with that measured in Xiushui63.
      Exogenous GSH significantly alleviated growth inhibition in Xiushui63 under 5 MUM
      Cd and in both genotypes in 50 MUM Cd. External GSH significantly increased
      chlorophyll content, Pn, Fv/Fm, and Y(II) of plants exposed to Cd, but decreased
      Y(NPQ) and the coefficient of non-photochemical quenching (qN). GSH addition
      significantly increased root GSH content in plants under Cd exposure (except day
      5 of 50 MUM Cd) and induced up-regulation in PCs of 5 MUM-Cd-treated Bing97252
      throughout the 15-day and Xiushui63 of 5-day exposure. The results suggest that
      genotypic difference in the tolerance to Cd stress was positively linked to the
      capacity in elevation of GSH and PCs, and that alleviation of Cd toxicity by GSH
      is related to significant improvement in chlorophyll content, photosynthetic
      performance, and root GSH levels.

PMID- 21191822
TI  - Pulmonary sarcoidosis developing fatal interstitial pneumonia-like lesions: a
      case report and literature review.

PMID- 21191823
TI  - Moyamoya disease and surgical intervention.
AB  - Stroke is an increasingly recognized cause of morbidity in the pediatric
      population. The incidence of ischemic stroke is 1.2 per 100,000 children. There
      are many known etiologies of childhood cerebral ischemia but moyamoya is one of
      the only ischemic conditions of childhood that can be effectively treated with
      surgery. Moyamoya disease is by definition idiopathic, whereas moyamoya syndrome
      refers to a similar disease course in conjunction with a known predisposing
      condition. The clinical manifestations and disease progression are similar.
      Furthermore, surgical treatment has been shown to be efficacious and safe in the
      treatment of moyamoya.

PMID- 21191824
TI  - Chemotherapy-induced neuropathy.
AB  - OPINION STATEMENT: Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of
      the most severe and unpredictable side effects of modern anticancer treatment. In
      recent years, a clear understanding of the importance of an integrated approach
      to CIPN has become evident, and efforts are increasing to better characterize its
      features and to identify more accurate methods to report and grade its
      occurrence. The clinically relevant impact of CIPN on cancer patients has been
      known for a long time, but knowledge of its pathogenetic aspects is still very
      limited. This incomplete knowledge is one of the major limitations in identifying
      targets for evidence-based neuroprotective strategies. Nevertheless, several
      studies have been devoted to the prevention or at least the effective treatment
      of symptoms secondary to peripheral nerve damage and to the early identification
      of patients at high risk of developing severe CIPN. Unfortunately, none of these
      studies has been successful and the optimal management of CIPN patients is still
      an unmet clinical need. Therefore, the modification of chemotherapy is currently
      the only available approach to limit the severity of neuropathy in the vast
      majority of patients. The indications for treatment modification are not
      universally accepted and they can differ among the various drugs. Generally,
      treatment modification should be considered as soon as symptoms and signs impair
      the daily life activities of the patient, but the possibility of a delayed
      worsening of CIPN after treatment withdrawal ("coasting") should always be
      considered, and delay of modification decisions should be avoided.

PMID- 21191825
TI  - Ossifying lesion of the rotator interval.
AB  - We report a case of a 15-year-old girl who presented with pain and swelling in
      the right shoulder. Imaging studies showed an inflammatory process well limited
      at the rotator interval. Open biopsy showed an osteogenic process that was
      evident in the postoperative X-rays. Two-year follow-up showed a mature
      ossification at the rotator interval.

PMID- 21191826
TI  - Regulation of neuronal activation by Alpha2A adrenergic receptor agonist.
AB  - Stress factors induce neuronal activation in brain areas that are related to
      anxiety and fear. High doses of caffeine induce neuronal activation with Ca2+
      influx followed by expression of the immediate early gene c-fos. In the present
      study, we investigated c-Fos protein expression in stress-responsive brain areas
      induced by caffeine, as well as the role of alpha2A receptor in the regulation of
      neuronal activation. Immunohistochemical analysis showed that an acute effect of
      caffeine induced c-Fos protein expression in the hippocampus, the bed nucleus of
      stria terminalis (BNST), the lateral septum, the basolateral and central
      amygdala, the paraventricular hypothalamic nucleus (PVN), the locus coeruleus,
      and the lateral parabrachial nucleus (LPBN). However, c-Fos expression was
      attenuated after repeated treatment of caffeine, spaced 24 h apart, compared to a
      single acute effect. Alpha2A receptor activation with the agonist guanfacine
      attenuated the acute effect of caffeine in terms of c-Fos expression in neurons
      in the CA1-CA3 areas of hippocampus, the locus coeruleus and the LPBN as compared
      with effect of caffeine alone, whereas the number of c-Fos expressing neurons
      increased in the lateral septum, the dorsal BNST, the central amygdala, and the
      PVN, areas that are densely innervated by noradrenergic neurons. Guanfacine alone
      induced c-Fos protein expression in neurons in the central amygdala, the dorsal
      BNST, the PVN, the LPBN, and the caudal nucleus of the solitary tract. Guanfacine
      alone also induced phosphorylation of extracellular signal-regulated kinase 1/2
      (ERK1/2) in neurons expressing c-Fos in the dorsal BNST, the central amygdala,
      and the LPBN. These results suggest that alpha2A receptor activation modulates
      synaptic transmission in neuronal circuits that are correlated with stress in
      vivo.

PMID- 21191827
TI  - [Malignant transformation of plantar ulcers in leprosy: experience of National
      Leprosy Center in Casablanca].
AB  - Malignant degeneration is a late complication of plantar ulcers in leprosy. The
      objective of this study is to describe and analyze the epidemiological, clinical,
      and therapeutic aspects of this complication in Morocco. A retrospective study
      was conducted from January 2000 to December 2009 at the National Center of
      Leprosy (CNL) in Casablanca. All our patients had a histological confirmation.
      Ten patients were included in this study. There were seven men and three women,
      with a mean age of 58.8 years. Six patients had a multibacillary form of leprosy
      and four had a paucibacillary form. The average duration of the plantar ulcers
      was 34.4 years. Clinical appearance at diagnosis was an ulcerative and vegetative
      tumor. Treatment was by radical amputation. Evolution was marked by metastatic
      spread in six patients. One patient died of disseminated disease. In Morocco,
      leprosy has been on the decline since 1990, but the occurrence of late
      complications in the leprosy patient as carcinoma of plantar ulcers persists.
      Prevention of these complications should be part of the national fight against
      leprosy.

PMID- 21191828
TI  - HPV prevalence and genotyping in the cervix of Chinese women.
AB  - The role of human papillomavirus (HPV) as an etiologic factor of cervical cancer
      has been firmly established, and prophylactic vaccines are now available and have
      been approved in many countries. Vaccination implies a promising future for
      cervical cancer prevention especially for countries with very limited access to
      screening. However, the vaccines are not accessible in mainland China at the
      moment, and much needs to be understood about the potential benefit when HPV
      vaccines are applied to Chinese women, and to make the vaccines more specific to
      Chinese women. This article reviews advanced multi-center, hospital/population
      based studies of most recent years, and aims to draw a definitive conclusion on
      HPV prevalence and genotyping in cervical cancer and precancerous lesions in
      China from the aspect of study population, geographic areas and time period.

PMID- 21191829
TI  - Clinical significance of human papilloma virus infection in the cervical lesions.
AB  - Cervical lesions have been regarded as the common and frequently occurring
      diseases in China. Recently, the morbidity and youth tendency of cervical cancer
      have gradually increased. Cervical cancer, related with human papilloma virus
      (HPV) infection, has been one of the severest diseases threatening health and
      life of women, and is an infectious disease. The universality of HPV infection in
      the reproductive tract should not be ignored. The well-known risk factors of HPV
      infection in cervical lesions consist of high-risk sexual behaviors,
      immunosuppression, age, contraceptive methods, the concurrent infection of other
      sexually transmitted diseases, etc. The variation of cervical lesions induced by
      HPV infection is involved in the continuous pathological process, including the
      subclinical, latent, and persistent infection of high risk (HR)-HPV, chronic
      cervicitis with abnormal results of cytological examination, cervical
      intraepithelial neoplasia (CIN), and cervical cancer. The outcome of patients
      with HPV infection is influenced by many factors, such as HPV subtype dominance,
      persistent HPV infection, HPV loading dose, and multiple HPV infection.
      Controlling HR-HPV persistent infection should be an important strategy for
      reducing cervical lesions.

PMID- 21191830
TI  - Current situation and development of prenatal diagnosis in China.
AB  - Prenatal screening and diagnosis are major methods for control of birth defects,
      which is a very important problem in China. Here, we review current situation and
      development of prenatal screening and diagnosis in mainland China, including
      prenatal screening and prenatal diagnosis of fetal chromosome abnormalities, non
      invasive prenatal diagnostic techniques and prenatal diagnosis of monogenic
      diseases, polygenic disease and congenital metabolic diseases. We also discuss
      epidemiology of birth defects and genetic diseases in China and related ethical
      issues of prenatal diagnosis.

PMID- 21191831
TI  - Pathogenesis, diagnosis, and treatment of recurrent spontaneous abortion with
      immune type.
AB  - Recurrent spontaneous abortion (RSA), defined as three or more consecutive
      pregnancy losses before 20 weeks of gestation, is difficult to treat in the
      clinical setting. It affects 1%-5% of women of reproductive age. In the
      investigations of immunopathogenesis, diagnosis, and treatment of RSA since the
      late 1980s, it was found that RSA was associated with abnormal maternal local or
      systemic immune response. The pathogenesis of autoimmune RSA was mainly
      associated with antiphospholipid antibody (APA), while that of alloimmune RSA was
      due to the disturbance of maternofetal immunological tolerance. Systemic
      etiological screening process and diagnosis systems of RSA with immune type were
      developed, and anticardiolipin (ACL or ACA) + anti-beta2-GP1 antibody combining
      multiple assays for effective diagnosis of RSA with autoimmune type was first
      established. According to the dynamic monitoring of clinical parameters before
      and during gestation, low-dose, short-course, and individual immunosuppressive
      therapy and lymphocyte immunotherapy for RSA with immune type were carried out.
      The outcomes of the offsprings of patients with RSA were followed up, and the
      safety and validity of the therapies were confirmed. The research achievement
      leads to great progress in the diagnosis and treatment of RSA in China.

PMID- 21191832
TI  - Polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a common gynecologic endocrinopathy. The
      pathogenesis of PCOS is associated with both heredity and environment. PCOS has
      adverse impacts on female endocrine, reproduction, and metabolism. PCOS can
      impact women's reproductive health, leading to anovulatory infertility and higher
      rate of early pregnancy loss. PCOS has additional metabolic derangements, such as
      insulin resistance, impaired glucose tolerance, and dyslipidemia. The risks of
      diabetes, cardiovascular disease, hypertension, metabolic syndrome, and
      endometrial cancer among PCOS patients are significantly increased as well.

PMID- 21191833
TI  - Family planning technical services in China.
AB  - Family planning is a basic state policy in China. Its aim is to control
      population growth and to enhance population quality. Technical services are the
      key measures for implementing the family planning policy. In order to ensure that
      people use safe, effective, and appropriate contraceptive methods based on the
      government's commitment, China has established countrywide family planning
      service networks down to the township level. The people can access various and
      convenient contraceptive services. In urban areas, all contraceptive services are
      free. The contraceptive prevalence rate in 2007 was 84.6%, the percentage of
      intrauterine device (IUD) was 52.3%, that of female sterilization was 32.3%, and
      that of vasectomy was 6.1%. This means that more than 90% of married childbearing
      couples were using long-term contraceptives. At the same time, the government
      gives priority to supporting research on contraceptive technology. Studies'
      results have provided scientific evidence for development, introduction, and
      expansion of contraceptive methods, and also for establishment and revision of
      the technical guidelines. Great efforts have been made in promoting "human
      oriented and client-centered" services during the recent ten years. Remarkable
      success has been achieved in improving the quality of technical services.

PMID- 21191834
TI  - How to judge the association of postmenopausal hormone therapy and the risk of
      breast cancer.
AB  - The relevance of postmenopausal hormone therapy (HT) for breast cancer risk has
      been long debated, although it is one of the most important barriers for women to
      accept HT. Various opinions have been reported from recent randomized clinical
      trials and epidemiological studies. These unanswered questions include: whether
      HT has a positive impact on breast cancer; whether risks of therapy with
      unopposed estrogen and combined estrogen-progestin are different; and whether
      different types and routes of estrogen and progestogens, as well as the duration
      and cessation of HT use, have different impacts on this disorder. Recently, there
      has been some good news such as the following: the currently available data do
      not provide sufficient evidence to prove a causal relationship between
      postmenopausal HT and breast cancer; breast cancer in postmenopausal women using
      HT usually has better prognosis than that of nonusers. In conclusion, HT is still
      the most effective method of relieving climacteric symptoms for many
      postmenopausal women. However, a possible risk of breast cancer associated with
      long-term HT usage should not be ignored. With respect to prevention of breast
      cancer, regular evaluation of individual breast cancer susceptibility and close
      follow-up through mammography and/or breast sonography are necessary strategies
      for the safety of HT use.

PMID- 21191835
TI  - High-intensity focused ultrasound tumor ablation: review of ten years of clinical
      experience.
AB  - High-intensity focused ultrasound (HIFU) is a technique to destroy tissue at
      depth within the body, selectively and without harming overlying and adjacent
      structures within the path of the beam because the ultrasonic intensity at the
      beam focus is much higher than that outside of the focus. Diagnostic ultrasound
      is the first imaging modality used for guiding HIFU ablation. In 1997, a patient
      with osteosarcoma was first successfully treated with ultrasound imaging-guided
      HIFU in Chongqing, China. Over the last decade, thousands of patients with
      uterine fibroids, liver cancer, breast cancer, pancreatic cancer, bone tumors,
      and renal cancer have been treated with ultrasound imaging-guided HIFU. Based on
      several research groups' reports, as well as our ten-year clinical experience, we
      conclude that this technique is safe and effective in treating human solid
      tumors. HIFU is a promising technique. Most importantly, HIFU offers patients
      another alternative when those patients have no other treatment available.

PMID- 21191836
TI  - Difference between 2 h and 3 h 75 g glucose tolerance test in the diagnosis of
      gestational diabetes mellitus (GDM): results from a national survey on prevalence
      of GDM.
AB  - The possibility of the 2 h oral glucose tolerance test (OGTT) as an alternative
      to the 3 h OGTT was investigated based on data from a national survey on
      pregnancy-associated diabetes. Data were retrieved from 4179 pregnant women who
      had OGTT performed after an abnormal 50 g glucose challenge test (GCT). All of
      the 4 glucose levels during their OGTT were collected and analyzed. According to
      American Diabetes Association (ADA) gestational diabetes mellitus (GDM)
      diagnostic criteria, among the 4179 pregnant women who required OGTT, 3429
      (82.1%) were normal and 750 (17.9%) were diagnosed as GDM. If the 3rd h glucose
      levels were omitted from OGTT, 79 cases of GDM (10.5%) would be overlooked. No
      trend was shown where women with more risk factors were more likely to be
      overlooked if the 3rd h test was omitted (chi2 for trend=0.038, P>0.05). No
      significant differences were found in the rate of cesarean section (CS), preterm
      births or macrosomia between the 79 cases and those with normal OGTT results and
      in the gestational weeks when OGTT was performed. It shows that in order to
      diagnose one woman with GDM, another 52 pregnant women would have an innocent 3rd
      h glucose test. Omission of the 3rd h glucose test in OGTT might be reasonable
      due to its convenience, better compliance and a small number of possibly miss
      diagnosed cases, and their pregnancy outcomes have no significant difference from
      those of normal pregnant women.

PMID- 21191837
TI  - Early diagnosis and therapeutic choice of Klebsiella pneumoniae liver abscess.
AB  - Nowadays, pyogenic liver abscess (PLA) is still a common and severe intra
      abdominal infection, and Klebsiella pneumoniae had emerged as the most common
      pathogenic bacteria worldwide in the past ten years. Our study aims to achieve an
      early pathogenic diagnosis and rational therapy modality for Klebsiella
      pneumoniae liver abscess (KLA) through clinical data analysis. A total of 197
      inpatients in Zhongshan Hospital, Shanghai, diagnosed as having liver abscess
      between March 2001 and September 2009 were enrolled. Patients with monomicrobial
      infection were divided into two groups: patients with K. pneumoniae liver abscess
      (KLA group, n=106) and those with non-Klebsiella pneumoniae liver abscess (NKLA
      group, n=56). A retrospective analysis was made between these two groups on the
      aspects of underlying diseases, clinical characteristics, laboratory data,
      culture results, and imaging findings. To evaluate the effects of different
      medical interventions, monomicrobial KLA patients were further divided into four
      subgroups (percutaneous liver aspiration, aspiration plus antibiotics flushing,
      aspiration plus retained catheter, and aspiration plus antibiotics flushing and
      retained catheter), and corresponding therapeutic effects were analyzed. KLA was
      more likely to occur in patients with coexisting diseases such as diabetes
      mellitus (53.77% vs 25.00%, P=0.001) and hepatic adipose infiltration (16.04% vs
      5.36%, P=0.029). Compared to NKLA group, clinical characteristics including
      abdominal pain (40.57% vs 57.14%, P=0.044), hypodynamia (19.81% vs 46.43%,
      P=0.001), and hepatomegaly (4.72% vs 14.29%, P=0.033) were much milder, but with
      a higher fasting blood glucose level (7.84+/-0.36 vs 5.76+/-0.30, P=0.001) on
      admission in KLA group. In addition, KLA abscess often appeared singly in the
      right lobe of the liver with gas forming nature (32.88% vs 13.51%, P=0.039),
      unsmooth rim (71.23% vs 40.54%, P=0.002), and dynamic septum enhancement (41.10%
      vs 16.22%, P=0.009). Compared to mono aspiration subgroup, additional antibiotic
      flushing could not further improve clinical outcomes of KLA patients (P>0.05);
      however, the retained catheter showed obvious advantage in reducing abscess
      diameter (34.38+/-3.25 mm vs 22.67+/-2.37 mm, P=0.017). It can be concluded that
      the strong association with diabetes, milder clinical symptoms, and gas-forming
      nature in CT images makes early pathogenic diagnosis of KLA possible.
      Comparatively, ultrasonography-guided percutaneous liver aspiration with retained
      catheter may be the most rational intervention modality of KLA.

PMID- 21191839
TI  - Inhibition of NF-kappa B can enhance Fas-mediated apoptosis in leukemia cell line
      HL-60.
AB  - This study explored the effects of nuclear factor-kappa B (NF-kappaB) inhibitor
      Bay 11-7082 on Fas/FasL system and Fas-mediated apoptosis in cell line HL-60
      cells. The mRNA and protein levels of Fas, FasL, and X-linked inhibitor of
      apoptosis protein (XIAP) were detected by reverse transcription-polymerase chain
      reaction (RT-PCR) and flow cytometry (FCM); the level of sFasL was evaluated by
      enzyme-linked immunosorbent assay (ELISA); and apoptosis was determined by FCM.
      After treatment with Bay 11-7082, the mRNA and protein levels of FasL and XIAP in
      HL-60 cells were significantly lower than in the controls (P<0.05), but the mRNA
      and protein levels of Fas and sFasL did not change significantly (P>0.05).
      Apoptotic rate of HL-60 cells treated with Bay 11-7082 was significantly higher
      than in the controls (P<0.05). Therefore, we conclude that Bay 11-7082 can
      enhance Fas-mediated apoptosis in HL-60 cells by downregulating FasL and XIAP
      levels.

PMID- 21191838
TI  - Effect of Salvia miltiorrhiza pretreatment on the CCK and VIP expression in
      hepatic ischemia-reperfusion-induced digestive tract congestion.
AB  - The inhibitory effect of different reperfusion periods 45 min following hepatic
      ischemia on the expression of cholecystokinin (CCK) and vasoactive intestinal
      peptide (VIP) in the jejunum and the effect of salvia miltiorrhiza pretreatment
      were investigated, and the possible mechanism and implications were explored.
      Eighty rats were randomly divided into four groups: normal control group (CO
      group), sham-operated group (SO group), ischemia/reperfusion (I/R) injury group
      (IR group) and salvia miltiorrhiza pretreatment group (SM group). The rat model
      of I/R was established by using a non-invasive artery clamp to clip (45 min) or
      relax the hepatic pedicle. In the SM group, saline (40 mL/kg) and salvia
      miltiorrhiza injection (6 g/kg) were injected via the tail vein 30 min before
      clipping the hepatic pedicle. In the SO group only the porta hepatis was
      dissected after laparotomy without clamping the hepatic pedicle. At 0, 3, 12, 24
      and 72 h post-reperfusion, respectively, upper jejunum samples were taken for
      immunohistochemistry of CCK and VIP. It was found that 0 h after I/R, the
      expression of CCK and VIP in the upper jejunum was upregulated. With prolongation
      of the reperfusion period, the expression of CCK and VIP was also increased,
      reached the peak at the 24th h, and gradually returned to the normal level at the
      72nd h after reperfusion. The levels of both CCK and VIP in the SM group were
      lower than those in the IR group. It is suggested that the digestive tract
      congestion injury caused by liver ischemia can upregulate the expression of CCK
      and VIP in the jejunum following reperfusion. Salviae pretreatment can partly
      reduce the increased expression of CCK and VIP in the jejunum in the same period,
      which might contribute to the early recovery of gastrointestinal motility.

PMID- 21191840
TI  - Effects of resistin on skeletal glucose metabolism.
AB  - Resistin is an adipokine highly related to insulin resistance (IR). The purpose
      of our research was to investigate how resistin influences skeletal glucose
      metabolism and explore its mechanisms. We constructed the recombinant plasmid
      pcDNA3.1 expressing resistin and then transfected it into C2C12 myocytes. The
      expression of resistin in C2C12 myocytes was detected by Western blotting.
      Glucose uptake was measured by 3H labeled glucose; glucose oxidation and glycogen
      synthesis was detected with 14C-labeled glucose. GLUT4 mRNA was measured by
      reverse transcription polymerase chain reaction (RT-PCR). We observed that
      resistin was expressed in transfected myocytes, and resistin decreased insulin
      induced glucose uptake rate by 28%-31% and inhibited the expression of GLUT4
      mRNA. However, there was no significant difference in basal glucose uptake, and
      glucose oxidation and glycogen synthesis remained unchanged in all groups. It is
      concluded that resistin inhibits insulin induced glucose uptake in myocytes by
      downregulating the expression of GLUT4 and it has no effects on glucose oxidation
      and glycogen synthesis. Our findings may provide a clue to understand the roles
      of resistin in the pathogenesis of skeletal IR.

PMID- 21191841
TI  - Autoimmune regulator regulates autophagy in THP-1 human monocytes.
AB  - The autoimmune regulator (AIRE) is a crucial factor for the induction of central
      tolerance, and mutations in this gene lead to abnormal immune responses. However,
      the role of AIRE in autophagy in immune cells, especially in monocytes, is
      obscure. In the present study, we found that overexpression of AIRE in THP-1
      human monocytes resulted in increased endogenous light chain 3 (LC3)-II level and
      elevated LC3 positive vesicles. Moreover, an autophagy inhibitor or knockdown of
      AIRE by small interference RNA attenuated these effects. In contrast, the
      expression of p62/SQSTM1 remained unchanged in THP-1 cells after the
      corresponding treatment. Our findings indicate that AIRE plays a role in the
      regulation of autophagy in THP-1 human monocytes.

PMID- 21191842
TI  - The value of radionuclide hepatobiliary scintigraphy in combination with
      determination of bilirubin from duodenal drainage in differential diagnosis of
      infantile persistent jaundice.
AB  - The aim of this study was to investigate the value of technetium etifenin
      injection (99mTc-EHIDA) hepatobiliary scintigraphy in combination with
      determination of bilirubin from duodenal drainage in differential diagnosis
      between infantile hepatitis syndrome and biliary atresia. 99mTc-EHIDA
      hepatobiliary scintigraphy in combination with duodenal fluid examination was
      used for evaluation in 84 infants with persistent infantile jaundice. For
      diagnosing biliary atresia, the sensitivity and specificity of scintigraphy were
      100% and 74.5%, respectively; the sensitivity and specificity of scintigraphy in
      combination with duodenal fluid examination were 100% and 100%, respectively. In
      conclusion, hepatobiliary scintigraphy, which is a noninvasive, safe, valuable
      examination method, in combination with examination of duodenal fluid, is of
      value for the differential diagnosis between infantile hepatitis syndrome and
      biliary atresia.

PMID- 21191844
TI  - Production costs and animal welfare for four stylized hog production systems.
AB  - Nonhuman animal welfare is arguably the most contentious issue facing the hog
      industry. Animal advocacy groups influence the regulation of hog farms and induce
      some consumers to demand more humane pork products. Hog producers are
      understandably reluctant to improve animal well being unless the premium they
      extract exceeds the corresponding increase in cost. To better understand the
      relationship between animal welfare and production costs under different farm
      systems, this study investigates 4 stylized hog production systems. The results
      show that increasing animal welfare for all hogs in the United States will
      increase retail pork prices by a maximum of 2% for a small welfare increase and
      5% for a large welfare increase. The cost of banning gestation crates measured by
      this study is lower than the consumer willingness-to-pay from other studies.

PMID- 21191843
TI  - Natural history of HIV infection in former plasma donors in rural China.
AB  - Patients infected through commercial blood-selling practices (former plasma
      donors, FPDs) in China represent a unique patient population compared to
      individuals infected through sexual contact or intravenous drug use. FPDs all
      have an approximate time of human immunodeficiency virus (HIV) infection during
      the mid-1990s. Few studies about the natural history of HIV infection in these
      patients were performed. The current study focuses on characterizing the duration
      of asymptomatic infection as well as the time to disease and mortality of
      infected FPDs in China. A retrospective cohort study was conducted based on data
      collected from 5484 HIV-1 infected FPDs in Shangcai county, Henan province.
      Kaplan-Meier analysis was applied to estimate the asymptomatic duration from the
      time of infection to the onset of AIDS as well as the survival period from the
      onset of AIDS to the time of death. The estimated median asymptomatic phase was
      about 9.21 years, which is similar to that reported in other developing countries
      in Africa. The estimated median life span after the onset of symptoms was about
      9.91 months, which is notably shorter than life spans reported elsewhere. This is
      the first large-scale retrospective study on the natural history of HIV infection
      in FPDs in rural China. The findings not only provide valuable insight into an
      understudied population, but should also serve as an important reference for
      patient management and care.

PMID- 21191845
TI  - Impact of zoo visitors on the fecal cortisol levels and behavior of an endangered
      species: Indian blackbuck (Antelope cervicapra L.).
AB  - This study investigated behavioral activities (resting, moving, aggressive,
      social, and reproductive behavior) and fecal cortisol levels in 8 individually
      identified adult male blackbucks during periods of varying levels of zoo visitors
      (zero, low, high, and extremely high zoo visitor density). This study also
      elucidated whether zoo visitor density could disturb nonhuman animal welfare.
      This study analyzed fecal cortisol from the samples of blackbuck by
      radioimmunoassay and found significant differences (p < .05) for time the animals
      devoted to moving, resting, aggressive, reproductive, and social behavior on days
      with high and extremely high levels of zoo visitors. The ANOVA with Duncan's
      Multiple Range Test test showed that the fecal cortisol concentration was higher
      (p < .05) during the extremely high (137.30 +/- 5.88 ng/g dry feces) and high
      (113.51 +/- 3.70 ng/g dry feces) levels of zoo visitor density. The results of
      the study suggest that zoo visitor density affected behavior and adrenocortical
      secretion in Indian Blackbuck, and this may indicate an animal welfare problem.

PMID- 21191846
TI  - Food preference, keeper ratings, and reinforcer effectiveness in exotic animals:
      the value of systematic testing.
AB  - Food preference describes the behavior of selecting between items for
      consumption; reinforcer effectiveness is the functional effect of that item in
      controlling behavior. Food preference and reinforcer effectiveness were examined
      in giant pandas (Ailuropoda melanoleuca) and African elephants (Loxodonta
      africana). A pairwise comparison between food items was used to assess food
      preference. High-, moderate-, and low-preference items were selected and tested
      for reinforcer effectiveness. High-preference items controlled behavior more
      effectively than less-preferred items. Caregiver ratings of food preferences were
      also collected for each subject, but these reports did not necessarily coincide
      with actual subject preferences. Caregiver ratings correlated with the food
      preferences of only 1 individual of each species; thus, preferences of 1 nonhuman
      animal may be falsely generalized to all animals of that species. Results suggest
      that food choice and reinforcer effectiveness should be investigated empirically
      and not rely on anecdotal reports.

PMID- 21191847
TI  - Social life of captive Asian elephants (Elephas maximus) in Southern India:
      implications for elephant welfare.
AB  - Asian elephants in the wild live in complex social societies; in captivity,
      however, management often occurs in solitary conditions, especially at the
      temples and private places of India. To investigate the effect of social
      isolation, this study assessed the social group sizes and the presence of
      stereotypies among 140 captive Asian elephants managed in 3 captive systems
      (private, temple, and forest department) in Tamil Nadu, India, between 2003 and
      2005. The majority of the facilities in the private (82%) and temple (95%)
      systems held a single elephant without opportunity for social interaction. The
      forest department managed the elephants in significantly larger groups than the
      private and temple systems. Among the 3 systems, the proportion of elephants with
      stereotypies was the highest in temple (49%) followed by private system (26%) and
      the forest department facility (6%); this correlates with the social isolation
      trend observed in the 3 systems and suggests a possible link between social
      isolation and abnormal elephant behavior separate from other environmental
      factors. The results of this study indicate it would be of greater benefit to
      elephant well being to keep the patchily distributed solitary temple and private
      elephants who are socially compatible and free from contagious diseases in small
      social groups at "common elephant houses" for socialization.

PMID- 21191848
TI  - What's in a name? Perceptions of stray and feral cat welfare and control in
      Aotearoa, New Zealand.
AB  - New Zealanders (n = 354) rated the acceptability of lethal and nonlethal cat
      control methods and the importance of conservation and welfare. Lethal control
      was more acceptable for feral cats than strays; for nonlethal control, the
      inverse was true. More than concern for the welfare of cats subjected to control,
      perceived conservation benefits, risk of disease transfer, and companion cat
      welfare dictated the acceptability of control measures. Similarly, the welfare
      consideration for groups of cats differed, transitioning from companion (highest)
      to feral (lowest). Differences in attitudes toward acceptability of control
      methods were evident. In particular, nonhuman animal professionals ranked lethal
      control as more acceptable than did nonanimal professionals. Cat caregivers
      (owners) considered both conservation and welfare issues of greater importance
      than did nonowners. Owners ranked the acceptability of nonlethal control methods
      higher for stray cats, but not feral, than did nonowners. This research indicates
      that the use of the terms stray and feral may have significant impact on cats in
      New Zealand. There is also a greater consideration of conservation values than of
      welfare in stray and feral cat control.

PMID- 21191849
TI  - Improving the welfare of captive macaques (Macaca sp.) through the use of water
      as enrichment.
AB  - This review evaluates the use of water as a tool for enriching the environments
      of macaques (Macaca sp.) in captivity. Many macaque species are known to swim and
      forage in water in the wild, and in-situ reports suggest that access to water
      promotes activity and cultural behavior. Yet, there is a relative dearth of
      information on water enrichment, covering only a small number of macaque species
      in both laboratory and zoo settings. Previous studies in captivity report high
      levels of usage of water enrichment as well as further behavioral benefits,
      including increases in play, exploratory behavior, and tool use. Subsequently,
      there is a clear need for more research on the potential benefits of water
      enrichment for both macaques and other primate species, especially given that
      small water troughs and pools provide an inexpensive method for enriching
      nonhuman primate lives in captivity.

PMID- 21191850
TI  - Sample size determination for testing equality in a cluster randomized trial with
      noncompliance.
AB  - For administrative convenience or cost efficiency, we may often employ a cluster
      randomized trial (CRT), in which randomized units are clusters of patients rather
      than individual patients. Furthermore, because of ethical reasons or patient's
      decision, it is not uncommon to encounter data in which there are patients not
      complying with their assigned treatments. Thus, the development of a sample size
      calculation procedure for a CRT with noncompliance is important and useful in
      practice. Under the exclusion restriction model, we have developed an asymptotic
      test procedure using a tanh(-1)(x) transformation for testing equality between
      two treatments among compliers for a CRT with noncompliance. We have further
      derived a sample size formula accounting for both noncompliance and the
      intraclass correlation for a desired power 1 - beta at a nominal alpha level. We
      have employed Monte Carlo simulation to evaluate the finite-sample performance of
      the proposed test procedure with respect to type I error and the accuracy of the
      derived sample size calculation formula with respect to power in a variety of
      situations. Finally, we use the data taken from a CRT studying vitamin A
      supplementation to reduce mortality among preschool children to illustrate the
      use of sample size calculation proposed here.

PMID- 21191851
TI  - On power and sample size calculation in ethnic sensitivity studies.
AB  - In ethnic sensitivity studies, it is of interest to know whether the same dose
      has the same effect over populations in different regions. Glasbrenner and
      Rosenkranz (2006) proposed a criterion for ethnic sensitivity studies in the
      context of different dose-exposure models. Their method is liberal in the sense
      that their sample size will not achieve the target power. We will show that the
      power function can be easily calculated by numeric integration, and the sample
      size can be determined by bisection.

PMID- 21191852
TI  - Conservative sample size estimation in nonparametrics.
AB  - Due to the uncertainty of the results of phase II trials, underpowered phase III
      trials are often planned. In recent literature the conservative approach for
      sample size estimation was proposed. Some authors, in the parametric framework,
      make use of the lower bound of the effect size for conservatively estimating the
      true power, and so the sample sizes. Here, we present a general bootstrap method
      for conservatively estimating, on the basis of phase II data, the sample size
      needed for a phase III trial. The method we propose is based on the use of
      nonparametric lower bounds for the true power of the test. A wide study is shown
      for comparing the performances of the new method in estimating the power of the
      Wilcoxon rank-sum test with those given by standard techniques based on the
      asymptotic normality of the test statistic. Results indicate that when the phase
      II sample size is around the ideal sample size for the phase III, the bootstrap
      provides better results than the other techniques. Since the method is general,
      it could be used for planning clinical trials for testing superiority, for
      testing noninferiority, and for more complicated situations, e.g., for testing
      multiple endpoints.

PMID- 21191853
TI  - Statistical inferences from formaldehyde DNA-protein cross-link data: improving
      methods for characterization of uncertainty.
AB  - Physiologically based pharmacokinetic (PBPK) modeling has reached considerable
      sophistication in its application to pharmacological and environmental health
      problems. Yet, mature methodologies for making statistical inferences have not
      been routinely incorporated in these applications except in a few data-rich
      cases. This paper demonstrates how improved statistical inference on estimated
      model parameters from both frequentist and Bayesian points of view can be
      routinely carried out. We work with a previously developed PBPK model for the
      formation and disposition of DNA-protein cross-links formed by inhaled
      formaldehyde in the nasal lining of rats and rhesus monkeys. We purposefully
      choose this model because it is based on sparse time-course data.

PMID- 21191854
TI  - An efficient algorithm to determine the optimal two-stage randomized multinomial
      designs in oncology clinical trials.
AB  - Sun et al. (2009) proposed an optimal two-stage randomized multinomial design
      that incorporates both response rate (RR) and early progression rate (EPR) in
      designing phase II oncology trials. However, determination of the design
      parameters in their approach requires evaluating huge numbers of combinations
      among possible values of design parameters, and thus requires highly intensive
      computation. In this paper we develop an efficient algorithm to identify the
      optimal two-stage randomized multinomial designs in phase II oncology clinical
      trials comparing a treatment arm to a control arm. The proposed algorithm
      substantially reduces the computation intensity via an approximation method. Some
      other techniques are also used to further improve its efficiency. Examples show
      that the proposed algorithm has more than a 90% reduction in computation time
      while having an acceptably low approximation error. This may enhance usage of the
      optimal two-stage multinomial design in clinical trials and also make it feasible
      to extend the design to more complicated scenarios.

PMID- 21191855
TI  - Estimating area under the curve and relative exposure in a pharmacokinetic study
      with data below quantification limit.
AB  - Area under the drug-concentration-over-time curve (AUC) is an important endpoint
      for many phase I/II clinical trials and laboratory assays. Drug concentrations
      are measured using laboratory assays with a lower limit of quantification (LLOQ).
      How to calculate AUC when some drug concentration data are below the LLOQ remains
      as a challenge. In this article, we develop a maximum likelihood method to
      estimate AUC and relative exposure (i.e., ratio of two AUCs) when data below LLOQ
      exists. We also compare the proposed method to several commonly used methods,
      including imputation with model-predicted values or ad hoc values (i.e., LLOQ,
      LLOQ/2, or zero) through a simulation study. The proposed method gives unbiased
      inference. Commonly used methods can provide biased estimation, especially when a
      large proportion of data is below LLOQ. Application to a case study is also
      presented.

PMID- 21191856
TI  - Two new covariate adjustment methods for non-inferiority assessment of binary
      clinical trials data.
AB  - In clinical trials, examining the adjusted treatment difference has become the
      preferred way to establish non-inferiority (NI) in cases involving a binary
      endpoint. However, current methods are inadequate in the area of covariate
      adjustment. In this paper, we introduce two new methods, nonparametric and
      parametric, of using the probability and probability (P-P) curve to address the
      issue of unadjusted categorical covariates in the traditional assessment of NI in
      clinical trials. We also show that the area under the P-P curve is a valid
      alternative for assessing NI using the adjusted treatment difference, and we
      compute this area using Mann-Whitney nonparametric statistics. Our simulation
      studies demonstrate that our proposed methods can not only control type I error
      at a predefined significance level but also achieve higher statistical power than
      those of traditional parametric and nonparametric methods that overlook covariate
      adjustment, especially when covariates are unbalanced in the two treatment
      groups. We illustrate the effectiveness of our methodology with data from
      clinical trials of a therapy for coronary heart disease.

PMID- 21191857
TI  - Test non-inferiority and sample size determination based on the odds ratio under
      a cluster randomized trial with noncompliance.
AB  - Because the odds ratio (OR) possesses certain desirable statistical properties,
      the OR has been recommended elsewhere to measure the relative treatment effect in
      establishing non-inferiority. For cost efficiency, we may often employ a cluster
      randomized trial (CRT), in which randomized units are clusters of patients.
      Furthermore, it is not uncommon to encounter data in which there are patients not
      complying with their assigned treatment. Under the Dirichlet multinomial model,
      we have developed a test statistic for assessing non-inferiority based on the OR
      between two treatments under a CRT with noncompliance. We have further derived a
      sample size formula accounting for both noncompliance and the intraclass
      correlation for a desired power 1 - beta of detecting non-inferiority with
      respect to the OR at a nominal alpha level. Using Monte Carlo simulation, we have
      evaluated the performance of the proposed test statistic and sample size formula.
      Finally, we use the CRT studying the effect of vitamin A supplementation on
      mortality among preschool children to illustrate the use of the sample size
      formula given here.

PMID- 21191858
TI  - Estimation strategies for reacting to the identification of an association
      between the genome and adverse drug reactions.
AB  - The availability of high-resolution genetic profiling raises the possibility,
      during the course of a drug development program, of discovering a subset of
      patients at particular risk of an adverse drug reaction who might be excluded
      from subsequent randomization into studies and identified as unsuitable for post
      licensing use. Such methods depend on the estimation of the risk of adverse drug
      reactions for patients with differing genetic profiles followed by an assessment
      of the risks and benefits of their exposure to the drug. In this paper we explore
      the performance of a number alternative statistical methods for the estimation of
      risk in terms of the success of the subsequent exclusion rules. The approaches
      were evaluated using a single-nucleotide polymorphism dataset concerning HIV
      patients at risk of hypersensitivity to the drug abacavir. Overall we found that
      a method based on LASSO performed better than the alternatives that we studied,
      which included a decision-theoretic Bayesian approach, and that its performance
      suggested suitability for its prospective implementation.

PMID- 21191859
TI  - Statistical efficiency in multiple-to-one comparison trials with optimal
      allocation ratio.
AB  - This paper discusses multiple-to-one comparison trials testing a multivalent
      vaccine product against multiple comparators with respect to immunologic
      responses. An optimal subject allocation ratio between the multivalent vaccine
      group and any of the comparators is introduced. This optimal ratio leads to
      higher statistical efficiency in terms of savings in sample size compared to
      equal allocation or any other allocation ratios. Several trial design scenarios
      are considered including assumptions of equal standardized effect size, unequal
      variance, and unequal standardized effect sizes of the multivalent vaccines
      versus the multiple comparators.

PMID- 21191861
TI  - A new outlier identification test for method comparison studies based on robust
      regression.
AB  - The identification of outliers in method comparison studies (MCS) is an important
      part of data analysis, as outliers can indicate serious errors in the measurement
      process. Common outlier tests proposed in the literature usually require a
      homogeneous sample distribution and homoscedastic random error variances.
      However, datasets in MCS usually do not meet these assumptions. In this work, a
      new outlier test based on robust linear regression is proposed to overcome these
      special problems. The LORELIA (local reliability) residual test is based on a
      local, robust residual variance estimator, given as a weighted sum of the
      observed residuals. The new test is compared to a standard test proposed in the
      literature by a Monte Carlo simulation. Its performance is illustrated in
      examples.

PMID- 21191860
TI  - Distribution of odds ratio in 2 * 2 contingency table: adjustment for
      correlation.
AB  - The Log-odds ratio for 2 * 2 contingency tables is often approximated by a normal
      distribution with an approximated variance. Hwang and Biswas (2008) illustrated
      that the standard expression for the variance should be modified in the presence
      of correlation. They also provided an adjustment to this variance expression when
      a single 2 * 2 table is available with matched-pair data. In this present paper,
      we first provide the required adjustment for multiple 2 * 2 tables, theoretically
      and also with reference to some data examples. We illustrate that this variance
      adjusted normal approximation is a better approximation for such data. We provide
      two examples, one of which came from a late-phase clinical trial. As the
      theoretical development of this research depends on the existence of a bivariate
      binomial distribution, a multivariate (and hence bivariate) binomial distribution
      is motivated and derived. We then provide a suitably correlation adjusted Mantel
      Haenszel test procedure.

PMID- 21191865
TI  - Adsorption and desorption variability of four herbicides used in paddy rice
      production.
AB  - This investigation was performed to determine the effect of physicochemical soil
      properties on penoxsulam, molinate, bentazon, and MCPA adsorption-desorption
      processes. Four soils from Melozal (35 degrees  43' S; 71 degrees  41' W), Parral
      (36 degrees  08' S; 71 degrees  52' W), San Carlos (36 degrees  24' S; 71 degrees
      57' W), and Panimavida (35 degrees  44' S; 71 degrees  24' W) were utilized.
      Herbicide adsorption reached equilibrium after 4 h in all soils. The Freundlich L
      type isotherm described the adsorption process, which showed a high affinity
      between herbicides and sorption sites mainly because of hydrophobic and H-bonds
      interaction. Penoxsulam showed the highest adsorption coefficients (4.23 +/- 0.72
      to 10.69 +/- 1.58 mL g-1) and were related to soil pH. Molinate showed K(d)
      values between 1.72 +/- 0.01 and 2.3 +/- 0.01 mL g-1 and were related to soil pH
      and organic matter, specifically to the amount of humic substances. Bentazon had
      a high relationship with pH and humic substances and its K(d) values were the
      lowest, ranging from 0.11 +/- 0.01 to 0.42 +/- 0.01 mL g-1. MCPA K(d) ranged from
      0.14 +/- 0.02 to 2.72 +/- 0.01 mL g-1, however its adsorption was related to
      humic acids and clay content. According to these results, the soil factors that
      could explain the sorption process of the studied herbicides under paddy rice
      soil conditions, were principally humic substances and soil pH. Considering the
      sorption variability observed in this study and the potential risk for
      groundwater contamination, it is necessary to develop weed rice management
      strategies that limit use of herbicides that exhibit low soil adsorption in areas
      with predisposing conditions to soil leaching.

PMID- 21191866
TI  - Mineralization and degradation of glyphosate and atrazine applied in combination
      in a Brazilian Oxisol.
AB  - The aim of this study was to investigate the behavior of the association between
      atrazine and glyphosate in the soil through mineralization and degradation tests.
      Soil treatments consisted of the combination of a field dose of glyphosate (2.88
      kg ha-1) with 0, 1/2, 1 and 2 times a field dose of atrazine (3.00 kg ha-1) and a
      field dose of atrazine with 0, 1/2, 1 and 2 times a field dose of glyphosate. The
      herbicide mineralization rates were measured after 0, 3, 7, 14, 21, 28, 35, 42,
      49, 56 and 63 days of soil application, and degradation rates after 0, 7, 28 and
      63 days. Although glyphosate mineralization rate was higher in the presence of 1
      (one) dose of atrazine when compared with glyphosate alone, no significant
      differences were found when half or twice the atrazine dose was applied, meaning
      that differences in glyphosate mineralization rates cannot be attributed to the
      presence of atrazine. On the other hand, the influence of glyphosate on atrazine
      mineralization was evident, since increasing doses of glyphosate increased the
      atrazine mineralization rate and the lowest dose of glyphosate accelerated
      atrazine degradation.

PMID- 21191867
TI  - Mitigation of dimethazone residues in soil and runoff water from agricultural
      field.
AB  - Dimethazone, also known as clomazone [2-[(2-chlorophenyl) methyl]- 4,4-dimethyl-3
      isoxaolidinone] is a pre-emergent nonionic herbicide commonly used in
      agriculture. A field study was conducted on a silty-loam soil of 10 % slope to
      monitor off-site movement and persistence of dimethazone in soil under three
      management practices. Eighteen plots of 22 x 3.7 m each were separated using
      stainless steel metal borders and the soil in six plots was mixed with municipal
      sewage sludge (MSS) and yard waste (YW) compost (MSS+YW) at 15 t acre-1 on dry
      weight basis, six plots were mixed with MSS at 15 t acre-1, and six unamended
      plots (NM) were used for comparison purposes. The objectives of this
      investigation were to: (i) monitor the dissipation and half-life (T1/2) of
      dimethazone in soil under three management practices; (ii) determine the
      concentration of dimethazone residues in runoff and infiltration water following
      natural rainfall events; and (iii) assess the impact of soil amendments on the
      transport of NO3, NH4, and P into surface and subsurface water. Gas
      chromatography/mass spectrometery (GC/MS) analyses of soil extracts indicated the
      presence of ion fragments at m/z 125 and 204 that can be used for identification
      of dimethazone residues. Intitial deposits of dimethazone varied from 1.3 MUg g-1
      dry native soil to 3.2 and 11.8 MUg g-1 dry soil in MSS and MSS+YW amended soil,
      respectively. Decline of dimethazone residues in the top 15 cm native soil and
      soil incorporated with amendments revealed half-life (T1/2) values of 18.8, 25.1,
      and 43.0 days in MSS+YW, MSS, and NM treatments, respectively. Addition of MSS+YW
      mix and MSS alone to native soil increased water infiltration, lowering surface
      runoff water volume and dimethazone residues in runoff following natural rainfall
      events.

PMID- 21191868
TI  - Realistic approach of pesticide residues and French consumer exposure within
      fruit & vegetable intake.
AB  - The increase of fruit and vegetable (F&V) intake contributes to the prevention of
      chronic diseases, but could also significantly increase pesticide exposure and
      may thus be of health concern. Following a previous pesticide exposure assessment
      study, the present study was carried out to determine actual levels of pesticides
      within 400 g of F&V intake and to evaluate consumer risk. Forty-three Active
      Substances (AS) exceeding 10 % of the Acceptable Daily Intake (ADI) in balanced
      menus established for our previous theoretical study were considered. Fifty-six
      pooled food samples were analyzed: 28 fruit samples and 28 vegetable samples.
      Pesticide values were compared to Maximum Residue Levels (MRL) and to the
      "toxicological credit" derived from ADI. It was observed that 23 out of the 43
      retained AS were never detected, 5 were detected both in F&V samples, 12 only in
      fruits and 3 only in vegetables. The most frequently detected AS were
      carbendazim, iprodione and dithiocarbamates. When detected, AS were more
      frequently found in fruit samples (74 %) than in vegetable samples (26 %). A
      maximum of 3 AS were detected at once in a given sample. Overall, we observed 8
      and 14 overruns of the MRL in 1204 measures in pooled vegetable and fruit
      samples, respectively (0.7 % and 1.2 % of cases, respectively). Chronic exposure
      for adults was the highest for dithiocarbamates but did not exceed 23.7 % of the
      ADI in F&V. It was concluded that raising both F&V consumption up to 400 g/day
      (~5 F&V/day) according to recommendations of the national health and nutrition
      plan, does not induce pesticide overexposure and should not represent a risk for
      the consumer.

PMID- 21191869
TI  - One love: explicit monogamy agreements among heterosexual young adult couples at
      increased risk of sexually transmitted infections.
AB  - HIV prevention strategies among couples include condom use, mutual monogamy, and
      HIV testing. Research suggests that condom use is more likely with new or casual
      partners, and tends to decline as relationships become steady over time. Little
      is known, however, about explicit mutual monogamy agreements and HIV testing
      within heterosexual couples. This study used data from 434 young heterosexual
      couples at increased risk of HIV and sexually transmitted infections (STIs) to
      assess (a) couple concordance on perceptions of a monogamy agreement, sustained
      monogamy, and HIV testing; and (b) the associations of relationship and
      demographic factors with monogamy agreement, sustained monogamy, and HIV testing.
      Results indicated only slight to fair agreement within couples on measures of
      monogamy agreement and sustained monogamy. Overall, 227 couples (52%) concurred
      that they had an explicit agreement to be monogamous; of those, 162 (71%) had
      sustained the agreement. Couples with greater health protective communication and
      commitment were more likely to have a monogamy agreement. Couples of Latino and
      Hispanic ethnicity and those with children were less likely to have a monogamy
      agreement. Only commitment was related to sustained monogamy. Having children,
      greater health protective communication, and perceived vulnerability to HIV and
      STIs were associated with HIV testing within the couple.

PMID- 21191871
TI  - Few improvements in the journal.

PMID- 21191872
TI  - [Prevalence of ESBL-positive enterobacteriaceae in large moravian hospitals
      (Czech Republic)].
AB  - BACKGROUND: bacterial infections have become an important issue in current
      medicine. Recently, their frequency and severity have significantly increased as
      a result of the rising number of resistant bacteria. One of important mechanisms
      of resistance is production of broad-spectrum beta-lactamases, namely the ESBL
      type. The study aimed at determining the frequency of ESBL-positive
      Enterobacteriaceae in three large hospitals in Moravia, the eastern part of the
      Czech Republic. MATERIAL AND METHODS: enterobacteriaceae were isolated from
      clinical material obtained from patients hospitalized in the University Hospital
      Olomouc, Teaching Hospital Ostrava and Bata Regional Hospital Zlin throughout
      2009. Standard microbiology techniques were used for identification. The
      production of ESBLs was determined by the modified Double-Disk Synergy Test. ESBL
      positive isolates of Escherichia coli from ICU patients were subjected to basic
      genetic analysis. RESULTS AND CONCLUSION: during the study period, a total of
      12,922 strains from the Enterobacteriaceae family were detected. The ESBL
      phenotype was found in 907 cases, i.e. 7 % of all isolates. The most prevalent
      species of ESBL-producing Enterobacteriaceae were Klebsiella pneumoniae,
      Klebsiella oxytoca and Escherichia coli. A comparison of general wards and ICUs
      revealed a higher percentage of ESBL-positive strains of Klebsiella pneumoniae
      and a lower proportion of ESBL-positive Escherichia coli isolates in intensive
      care patients. When assessing the patients' clinical material, ESBL-producing
      strains were most frequently detected in urine. Genetic analysis of ESBL-positive
      Escherichia coli strains from ICU patients revealed the CTX-M type of ESBL
      production in most isolates.

PMID- 21191873
TI  - [Current clinical significance of anaerobic bacteremia].
AB  - OBJECTIVE: to estimate tje current clinical significance of anaerobic bacteremia
      in a group of Czech hospitals. MATERIAL AND METHODS: this retrospective analysis
      comprised 8 444 anaerobic blood cultures in patients admitted to four Czech
      hospitals between 2004 and 2007. RESULTS: in 16 patients, blood cultures yielded
      significant anaerobic bacteria. Thus, anaerobic bacteremia accounted for less
      than 2 % of clinically significant bacteremia. Four patients (18 %) died but none
      of the deaths could be clearly attributable to anaerobic bacteria in the
      bloodstream. The most common comorbidities predisposing to anaerobic bacteremia
      and the most frequent sources of infection were similar to those reported by
      other authors. The majority of anaerobic bacteremia cases were due to gram
      negative bacteria, followed by Clostridium perfringens and, surprisingly,
      Eubacterium spp. (particularly Eubacterium lentum). CONCLUSION: anaerobic
      bacteremia remains rare. The comparison of our data with those by other authors
      suggests that (despite the reported high mortality) the actual clinical
      significance of anaerobic bacteremia is rather controversial and that the
      anaerobic bacteremia might not correspond to more serious pathogenic role of the
      anaerobic bacteria as the source of infection.

PMID- 21191874
TI  - [Current options for antifungal therapy of invasive candidiasis in intensive care
      units].
AB  - Candidemia and invasive candidiasis are the most frequent mycoses in critically
      ill patients in intensive care units. Recently, the number of systemic antifungal
      agents has increased, leading to improved treatment options. Yet these infections
      remain to be characterized by poor prognosis and high mortality rates. The most
      important predisposing factors are yeast colonization of the mucosa or skin and
      damage to the integrity of the host's natural barriers. Early diagnosis of
      invasive candidiasis is difficult, since its clinical manifestations are not
      characteristic and the laboratory techniques are time-consuming and not
      completely reliable. The currently available treatments comprise three groups of
      antifungals: triazoles, polyenes and echinocandins. For its effectiveness, low
      toxicity and reasonable price, fluconazole is the most widespread drug currently
      used to treat systemic yeast infections. However, despite high treatment costs,
      echinocandins are becoming the drug of choice. The advantages are a broad
      spectrum of species, safe administration to patients with kidney and liver
      damage, minimal drug interactions and fungicidal effects. Candidemia may often be
      positively influenced by replacing an intravenous catheter. Despite earlier
      controversy, the latest treatment strategies clearly recommend its removal.
      Although antifungal prophylaxis lowers the incidence of invasive candidiasis, it
      is considered to be useful only if targeted to high-risk groups of patients.
      Empirical treatment of febrile patients not responding to broad-spectrum
      antibiotic therapy is only effective in wards with a higher incidence of systemic
      candidiasis, in patients with risk factors and if other causes are reliably
      excluded.

PMID- 21191875
TI  - [Kaposi's sarcoma].
AB  - Kaposi's sarcoma (KS) is an unusual form of tumor which in the era of HIV/AIDS
      pandemic is increasingly observed outside the original endemic areas. It was
      shown that the development of KS is in directly related to infection with human
      herpes virus 8 (HHV-8). The pathophysiology of KS is complex and is influenced by
      HIV co-infection and by global cytokine interactions. Skin, gastrointestinal
      tract and respiratory organs are typically involved. A good therapeutic effect of
      combined antiretroviral therapy (cART) was documented. We provode a review of the
      current knowledge of the pathophysiology of and therapeutic options for KS and
      one clinical case.

PMID- 21191876
TI  - [Low response rate to a vaccination against hepatitis B in patients with end
      stage liver disease].
AB  - Hepatitis B vaccination was started in 41 patients with end-stage liver disease
      who were liver transplant candidates. Patients received three 20 microg or,
      starting from 1999, 40 microg doses of recombinant vaccine at 0, 2 and 4 weeks.
      Blood samples were obtained 4 weeks after vaccination or each revaccination;
      patients without protective hepatitis B surface antibodies (anti-HBs) were once
      or repeatedly revaccinated. Thirty-eight patients received at least 3 doses of
      vaccine. Protective anti-HBs level (>= 10 IU/l) was detected in 17 of 34 patients
      (50 %) after the third up to eight dose. No case of chronic HBsAg carrier status
      was detected. Immunisation against hepatitis B in persons with liver cirrhosis is
      associated with a poor response and new vaccines should be considered for these
      patients.

PMID- 21191877
TI  - Pyrethroid sorption to Sacramento River suspended solids and bed sediments.
AB  - Sorption of pyrethroid insecticides to solid materials will typically dominate
      the fate and transport of these hydrophobic compounds in aquatic environments.
      Batch reactor isotherm experiments were performed with bifenthrin and lambda
      cyhalothrin with suspended material and bed sediment collected from the
      Sacramento River, California, USA. These batch reactor experiments were performed
      with low spiking concentrations and a long equilibration time (28 d) to be more
      relevant to environmental conditions. Sorption to suspended material and bed
      sediment was compared to examine the role of differential sorption between these
      phases in the environmental transport of pyrethroids. The equilibrium sorption
      data were fit to the Freundlich isotherm model and fit with r(2)  > 0.87 for all
      experiments. Freundlich exponents ranged from 0.72 +/- 0.19 to 1.07 +/- 0.050,
      indicating sorption nonlinearity for some of the experimental conditions and
      linearity for others over the concentration range tested. The Freundlich capacity
      factors were larger for the suspended solids than for the bed sediments, and the
      suspended material had a higher specific surface area and higher organic carbon
      content compared to the bed sediment. Calculated organic carbon-normalized
      distribution coefficients were larger than those previously reported in the
      literature, by approximately an order of magnitude, and ranged from 10(6.16) to
      10(6.68) at an equilibrium aqueous concentration of 0.1 ug/L. Higher than
      expected sorption of pyrethroids to the tested materials may be explained by
      sorption to black carbon and/or mineral surfaces.

PMID- 21191878
TI  - Simulated watershed mercury and nitrate flux responses to multiple land cover
      conversion scenarios.
AB  - Water quality and toxic exposure science is transitioning towards analysis of
      multiple stressors rather than one particular environmental concern (e.g.,
      mercury) or a group of similarly reacting chemicals (e.g., nutrients). However,
      two of the most important water quality constituents affecting both human and
      ecosystem health today, reactive nitrogen (N(r) ) and methylmercury (MeHg), are
      often assessed separately for their independent effects on water quality. With
      the continued pressure of landscape modifications on water quality, a challenge
      remains in understanding the concurrent watershed flux response of both N(r) and
      MeHg to such physical stressors, particularly at the spatial scale (regional
      watersheds) and within the mixed land cover type systems that most decision
      making processes are conducted. We simulate the annual average and monthly flux
      responses of Hg (MeHg and total mercury [HgT]), NO(3) -N, and runoff to four land
      cover change scenarios in the Haw River Watershed (NC, USA), a headwater system
      in the Cape Fear River Basin. Fluxes are simulated using a process-based,
      spatially explicit watershed Grid-Based Mercury Model (GBMM) and a NO(3) -N
      watershed flux model we developed to link to GBMM. Results suggest that annual
      NO(3) -N and Hg fluxes increase and decrease concomitantly to land cover change;
      however, the magnitude of the changes in NO(3) -N, MeHg, HgT, and water fluxes
      vary considerably between different land cover conversion scenarios. Converting
      pasture land to a suburbanized landscape elicited the greatest increase in runoff
      and MeHg, HgT, and NO(3) -N fluxes among all four conversion scenarios. Our
      findings provide insight for multi-stressor ecological exposure research and
      management of coastal eutrophication resulting from elevated N(r) loadings and
      exposure risk due to elevated concentrations of MeHg in fish tissue.

PMID- 21191879
TI  - Enhanced adsorption of humic acids on ordered mesoporous carbon compared with
      microporous activated carbon.
AB  - Humic acids are ubiquitous in surface and underground waters and may pose
      potential risk to human health when present in drinking water sources. In this
      study, ordered mesoporous carbon was synthesized by means of a hard template
      method and further characterized by X-ray diffraction, N2 adsorption, transition
      electron microscopy, elemental analysis, and zeta-potential measurement. Batch
      experiments were conducted to evaluate adsorption of two humic acids from coal
      and soil, respectively, on the synthesized carbon. For comparison, a commercial
      microporous activated carbon and nonporous graphite were included as additional
      adsorbents; moreover, phenol was adopted as a small probe adsorbate. Pore size
      distribution characterization showed that the synthesized carbon had ordered
      mesoporous structure, whereas the activated carbon was composed mainly of
      micropores with a much broader pore size distribution. Accordingly, adsorption of
      the two humic acids was substantially lower on the activated carbon than on the
      synthesized carbon, because of the size-exclusion effect. In contrast, the
      synthesized carbon and activated carbon showed comparable adsorption for phenol
      when the size-exclusion effect was not in operation. Additionally, we verified by
      size-exclusion chromatography studies that the synthesized carbon exhibited
      greater adsorption for the large humic acid fraction than the activated carbon.
      The pH dependence of adsorption on the three carbonaceous adsorbents was also
      compared between the two test humic acids. The findings highlight the potential
      of using ordered mesoporous carbon as a superior adsorbent for the removal of
      humic acids.

PMID- 21191880
TI  - Comparison of acute and chronic toxicity of silver nanoparticles and silver
      nitrate to Daphnia magna.
AB  - Silver nanoparticles (AgNP) are now widely used as antibacterial products, and
      their potential toxicities in aquatic organisms are a matter of increasing
      concern. In the present study, we conducted experiments to reveal the acute and
      chronic toxicities of AgNP and its bioaccumulation from both aqueous and dietary
      sources in a model freshwater cladoceran, Daphnia magna. No mortality was
      observed in 48-h acute toxicity testing when the daphnids were exposed up to 500
      ug Ag/L as AgNP. The AgNP accumulation reached as high as 22.9 mg Ag/g dry weight
      at the highest AgNP concentration tested (500 ug/L). In contrast, D. magna was
      extremely sensitive to free Ag ion (Ag(+) , added as AgNO(3) ), with a measured
      48-h 50% lethal concentration of 2.51 ug/L. Thus, any AgNP potential acute
      toxicity may be caused by the release of Ag(+) into the solution. During the 21-d
      chronic exposure, dietborne AgNO(3) had the most significant influence on
      reproduction, whereas waterborne AgNP had the most significant inhibition on
      growth. Significant delay and decrease of reproduction in daphnids exposed to
      dietborne AgNO(3) occurred at a dissolved Ag concentration of 0.1 ug/L added to
      the algae. Significant inhibitions of growth and reproduction were also found for
      the AgNP exposure, with the lowest observed effective concentration of 5 ug/L and
      50 ug/L, respectively. Chronic effects of AgNP were probably caused by the low
      food quality of algae associated with AgNP and the low depuration of ingested
      AgNP. Environmental risk assessments of AgNP should therefore include tests on
      the chronic toxicity to aquatic organisms as well as the direct and indirect
      effects of AgNP resulting from the release of Ag(+) into the environment.

PMID- 21191881
TI  - Optimal conditions for stability of photoemission and freeze drying of two
      luminescent bacteria for use in a biosensor.
AB  - Bioluminescent bacteria have been used for many years for biotoxicological
      analysis. One of the main concerns with this microorganism is the low
      experimental repeatability when subjected to external factors. The aim of the
      present study was to obtain accurate, sensitive, and repeatable measurements with
      stable signals (during the detection and over days) for application in a water
      analysis device for the detection of pollutants. Growth conditions were tested
      and optimized. An optimal freeze-drying procedure for the constitutive
      bioluminescent bacteria Vibrio fischeri and Photobacterium phosphoreum was
      developed. The luminescence stability after rehydration was also investigated.
      Freeze drying was found to be a critical process in survival and signal stability
      of luminescent bacteria; for this reason, different suspension fluids and various
      bacterial pellet/suspension fluid ratios (g/ml) were evaluated. The toxicity of
      heavy metals and organic compounds in water was determined to investigate the
      applicability of a test based on bacteria obtained in this way, comparing the
      data with legal limits. A scale-up process was developed with industrial
      technology: freeze-dried bacteria that emitted a stable luminous signal after
      rehydration were obtained. Moreover, the median effective concentration (EC50)
      was calculated with these bacteria.

PMID- 21191882
TI  - Development of a polydimethylsiloxane film-based passive dosing method in the in
      vitro DR-CALUX(r) assay.
AB  - In bioassays, exposure concentrations of test compounds are usually expressed as
      nominal concentrations. As a result of various processes, such as adsorption,
      degradation, or uptake, the actual freely dissolved concentration of the test
      compound may differ from the nominal concentration. The goal of the present study
      was to develop a method to dose passively the freely dissolved fraction of
      organic chemicals in an in vitro bioassay with adherent cells. To this end, a
      polydimethylsiloxane (PDMS) film-based method was developed for a reporter gene
      assay for dioxin-like compounds in a rat liver cell line. Polydimethylsiloxane
      films loaded with test compounds ensure that the concentration during exposure is
      in equilibrium and that the ratio between the concentration on the film and the
      concentration in medium is constant. Benzo[k]fluoranthene (BkF) was used as a
      model compound to develop the passive dosing method in transwell plates, which
      was further tested with a complex mixture, i.e., an extract prepared from a
      contaminated sediment. A higher dioxin-like activity was found when extracts were
      dosed by passive dosing with PDMS than when directly added to medium. Comparison
      with analysis of the concentration of BkF in medium shows that passive dosing of
      individual chemicals may not be necessary if freely dissolved concentrations are
      known. Use of PDMS for passive dosing of complex samples may represent a more
      realistic method for exposure in in vitro bioassays.

PMID- 21191883
TI  - Influence of water hardness and sulfate on the acute toxicity of chloride to
      sensitive freshwater invertebrates.
AB  - Total dissolved solids (TDS) represent the sum of all common ions (e.g., Na, K,
      Ca, Mg, chloride, sulfate, and bicarbonate) in freshwater. Currently, no federal
      water quality criteria exist for the protection of aquatic life for TDS, but
      because the constituents that constitute TDS are variable, the development of
      aquatic life criteria for specific ions is more practical than development of
      aquatic life criteria for TDS. Chloride is one such ion for which aquatic life
      criteria exist; however, the current aquatic life criteria dataset for chloride
      is more than 20 years old. Therefore, additional toxicity tests were conducted in
      the current study to confirm the acute toxicity of chloride to several
      potentially sensitive invertebrates: water flea (Ceriodaphnia dubia), fingernail
      clams (Sphaerium simile and Musculium transversum), snail (Gyraulus parvus), and
      worm (Tubifex tubifex), and determine the extent to which hardness and sulfate
      modify chloride toxicity. The results indicated a significant ameliorating effect
      of water hardness (calcium and magnesium) on chloride toxicity for all species
      tested except the snail; for example, the 48-h chloride median lethal
      concentration (LC50) for C. dubia at 50 mg/L hardness (977 mg Cl(-) /L) was half
      that at 800 mg/L hardness (1,836 mg Cl(-) /L). Conversely, sulfate over the range
      of 25 to 600 mg/L exerted a negligible effect on chloride toxicity to C. dubia.
      Rank order of LC50 values for chloride at a given water hardness was in the order
      (lowest to highest): S. simile < C. dubia < M. transversum < G. parvus < T.
      tubifex. Results of the current study support the contention that the specific
      conductivity or TDS concentration of a water body alone is not a sufficient
      predictor of acute toxicity and that knowledge of the specific ion composition is
      critical.

PMID- 21191884
TI  - An egg injection technique to evaluate the effect of polychlorinated biphenyls on
      the hatching success of the snapping turtle (Chelydra serpentina serpentina).
AB  - Embryos of oviparous organisms are exposed to contaminants by two pathways:
      contaminant uptake from the surrounding environment, and the transfer from female
      to offspring (maternal transfer). The initial source of contaminant exposure for
      most embryos is likely to be maternal transfer; therefore, maternal transfer
      studies are critical in determining the effects of contaminants on future
      populations. Injection of contaminants directly into eggs is one route of
      experimental contaminant exposure that permits controlled doses and potential
      reliable replication. This technique, however, has been used in the past with
      little success in reptiles. The objective of the present study was to evaluate
      egg injection as a means of mimicking maternal transfer of polychlorinated
      biphenyls (PCBs) to snapping turtle eggs. Eggs from several clutches were
      injected with a PCB solution and incubated at several temperatures and moisture
      levels to measure interactive effects of injection, environmental condition, and
      contaminant load on hatching success. The injection technique allowed for
      application of consistent and specific doses among replicates. Overall hatching
      success in this study was 61% and was as high as 71% within specific treatments.
      Hatching success was much higher in this study than in other studies using egg
      injections to mimic maternal transfer in chelonians and crocodilians.

PMID- 21191908
TI  - In search of the psychopathic sexuality taxon: indicator size does matter.
AB  - Recent research has suggested that a qualitatively distinct subtype of
      psychopathic sex offender can be identified via taxometric analyses (Harris et
      al., 2007). In this study we attempted to replicate the hypothesized psychopathic
      sexuality taxon in a group of 503 male sexual offenders using data from the
      Psychopathy Checklist-Revised (PCL-R:Hare, 2003) and five coercive and precocious
      sexuality items. Ambiguous to dimensional results were obtained when, in a
      replication of the Harris et al. (2007) study,dichotomized indicators were
      analyzed with summed input maximum covariance (MAXCOV). Clearly dimensional
      results, however, were obtained when higher correlating and more valid quasi
      continuous indicators were analyzed with traditional (input variables not summed)
      MAXCOV, and both dichotomous and quasi-continuous indicators were analyzed with
      mean above minus below a cut (MAMBAC) and latent-mode factor analysis (L-Mode).
      These results suggest that Harris et al. (2007) may have mistaken the random
      fluctuations of weakly correlating and poorly differentiating indicators for a
      taxon. Consistent with the vast majority of earlier research,our results suggest
      that psychopathy (with or without coercive and precocious sexuality) is a
      dimensional construct.

PMID- 21191982
TI  - ChemBioChem has come of age.

PMID- 21191984
TI  - Much ado about small molecules in biology and medicine.

PMID- 21191995
TI  - Modeling industrial centrifugation of mammalian cell culture using a capillary
      based scale-down system.
AB  - Continuous-flow centrifugation is widely utilized as the primary clarification
      step in the recovery of biopharmaceuticals from cell culture. However, it is a
      challenging operation to develop and characterize due to the lack of easy to use,
      small-scale, systems that can be used to model industrial processes. As a result,
      pilot-scale continuous centrifugation is typically employed to model large-scale
      systems requiring a significant amount of resources. In an effort to reduce
      resource requirements and create a system which is easy to construct and utilize,
      a capillary shear device, capable of producing energy dissipation rates
      equivalent to those present in the feed zones of industrial disk stack
      centrifuges, was developed and evaluated. When coupled to a bench-top, batch
      centrifuge, the capillary device reduced centrate turbidity prediction error from
      37% to 4% compared to using a bench-top centrifuge alone. Laboratory-scale
      parameters that are analogous to those routinely varied during industrial-scale
      continuous centrifugation were identified and evaluated for their utility in
      emulating disk stack centrifuge performance. The resulting relationships enable
      bench-scale process modeling of continuous disk stack centrifuges using an easily
      constructed, scalable, capillary shear device coupled to a typical bench-top
      centrifuge.

PMID- 21191998
TI  - Escherichia coli W as a new platform strain for the enhanced production of L
      valine by systems metabolic engineering.
AB  - A less frequently employed Escherichia coli strain W, yet possessing useful
      metabolic characteristics such as less acetic acid production and high L-valine
      tolerance, was metabolically engineered for the production of L-valine. The ilvA
      gene was deleted to make more pyruvate, a key precursor for L-valine, available
      for enhanced L-valine biosynthesis. The lacI gene was deleted to allow
      constitutive expression of genes under the tac or trc promoter. The ilvBN(mut)
      genes encoding feedback-resistant acetohydroxy acid synthase (AHAS) I and the L
      valine biosynthetic ilvCED genes encoding acetohydroxy acid isomeroreductase,
      dihydroxy acid dehydratase, and branched chain amino acid aminotransferase,
      respectively, were amplified by plasmid-based overexpression. The global
      regulator Lrp and L-valine exporter YgaZH were also amplified by plasmid-based
      overexpression. The engineered E. coli W (DeltalacI DeltailvA) strain
      overexpressing the ilvBN(mut) , ilvCED, ygaZH, and lrp genes was able to produce
      an impressively high concentration of 60.7 g/L L-valine by fed-batch culture in
      29.5 h, resulting in a high volumetric productivity of 2.06 g/L/h. The most
      notable finding is that there was no other byproduct produced during L-valine
      production. The results obtained in this study suggest that E. coli W can be a
      good alternative to Corynebacterium glutamicum and E. coli K-12, which have so
      far been the most efficient L-valine producer. Furthermore, it is expected that
      various bioproducts including other amino acids might be more efficiently
      produced by this revisited platform strain of E. coli.

PMID- 21191999
TI  - Compatible ionic liquid-cellulases system for hydrolysis of lignocellulosic
      biomass.
AB  - Ionic liquids (ILs) have been increasingly recognized as novel solvents for
      dissolution and pretreatment of cellulose. However, cellulases are inactivated in
      the presence of ILs, even when present at low concentrations. To more fully
      exploit the benefits of ILs it is critical to develop a compatible IL-cellulases
      system in which the IL is able to effectively solubilize and activate the
      lignocellulosic biomass, and the cellulases possess high stability and activity.
      In this study, we investigated the stability and activity of a commercially
      available cellulases mixture in the presence of different concentrations of 1
      ethyl-3-methylimidazolium acetate ([Emim][OAc]). A mixture of cellulases and beta
      glucosidase (Celluclast1.5L, from Trichoderma reesei, and Novozyme188, from
      Aspergillus niger, respectively) retained 77% and 65% of its original activity
      after being pre-incubated in 15% and 20% (w/v) IL solutions, respectively, at 50
      degrees C for 3 h. The cellulases mixture also retained high activity in 15%
      [Emim][OAc] to hydrolyze Avicel, a model substrate for cellulose analysis, with
      conversion efficiency of approximately 91%. Notably, the presence of different
      amounts of yellow poplar lignin did not interfere significantly with the
      enzymatic hydrolysis of Avicel. Using this IL-cellulase system (15% [Emim][OAc]),
      the saccharification of yellow poplar biomass was also significantly improved
      (33%) compared to the untreated control (3%) during the first hour of enzymatic
      hydrolysis. Together, these findings provide compelling evidence that [Emim][OAc]
      was compatible with the cellulase mixture, and this compatible IL-cellulases
      system is promising for efficient activation and hydrolysis of native biomass to
      produce biofuels and co-products from the individual biomass components.

PMID- 21192000
TI  - Biocatalytic process optimization based on mechanistic modeling of cholic acid
      oxidation with cofactor regeneration.
AB  - Reduction and oxidation of steroids in the human gut are catalyzed by
      hydroxysteroid dehydrogenases of microorganisms. For the production of 12
      ketochenodeoxycholic acid (12-Keto-CDCA) from cholic acid the biocatalytic
      application of the 12alpha-hydroxysteroid dehydrogenase of Clostridium group P,
      strain C 48-50 (HSDH) is an alternative to chemical synthesis. However, due to
      the intensive costs the necessary cofactor (NADP(+) ) has to be regenerated. The
      alcohol dehydrogenase of Thermoanaerobacter ethanolicus (ADH-TE) was applied to
      catalyze the reduction of acetone while regenerating NADP(+) . A mechanistic
      kinetic model was developed for the process development of cholic acid oxidation
      using HSDH and ADH-TE. The process model was derived by identifying the
      parameters for both enzymatic models separately using progress curve measurements
      of batch processes over a broad range of concentrations and considering the
      underlying ordered bi-bi mechanism. Both independently derived kinetic models
      were coupled via mass balances to predict the production of 12-Keto-CDCA with
      HSDH and integrated cofactor regeneration with ADH-TE and acetone as co
      substrate. The prediction of the derived model was suitable to describe the
      dynamics of the preparative 12-Keto-CDCA batch production with different initial
      reactant and enzyme concentrations. These datasets were used again for parameter
      identification. This led to a combined model which excellently described the
      reaction dynamics of biocatalytic batch processes over broad concentration
      ranges. Based on the identified process model batch process optimization was
      successfully performed in silico to minimize enzyme costs. By using 0.1 mM
      NADP(+) the HSDH concentration can be reduced to 3-4 uM and the ADH concentration
      to 0.4-0.6 uM to reach the maximal possible conversion of 100 mM cholic acid
      within 48 h. In conclusion, the identified mechanistic model offers a powerful
      tool for a cost-efficient process design.

PMID- 21192002
TI  - A unique and potent protein binding nature of liposome containing
      polyethylenimine and polyethylene glycol: a nondisplaceable property.
AB  - Most of the currently available targeting vectors are produced via the linkage of
      targeting molecules. However, the coupling process is complicated, and the
      covalent linkage may attenuate the activity of certain targeting molecules. In
      this study, we have developed a cationic liposome complexed with polyethylenimine
      and polyethylene glycol polymers (LPPC) that can capture various proteins without
      covalent conjugation. Characterizations of prepared LPPC revealed that the
      maximal-binding capacity was about 170 ug of bovine serum albumin to 40 ug of
      sphere-shaped LPPC (180 nm). The proteins were essentially located at or near the
      surface when analyzed by atomic force or transmission electron microscopy. We
      demonstrate that polyethylenimine was an essential component to bind the
      proteins. Upon the saturation of captured proteins, a given protein could not be
      displaced by other additional proteins and still retained its biological
      activity. Using a variety of functional proteins, we show some typical examples
      of the utility of incorporated beta-glucuronidase and antibodies onto the LPPC.
      The beta-glucuronidase can be used for the study of antigen-antibody
      interactions, whereas in studies with the antibody complex, we used anti-CD3 as
      an agonist to stimulate the proliferation of peripheral blood mononuclear cells
      via a receptor-mediated mechanism and anti-VEGFR for cell staining. In
      conclusion, the prepared LPPC can provide a platform to capture biologically and
      biochemically functional proteins on its surface for various applications, such
      as cell signaling, cell profiling, noncovalent enzyme-linked immunoassays, and
      others not mentioned.

PMID- 21192003
TI  - Preliminary approach of real-time monitoring in vitro matrix mineralization based
      on surface plasmon resonance detection.
AB  - Matrix mineralization is a terminal process in osteoblast differentiation, and
      several approaches have been introduced to characterize the process in tissues or
      cultured cells. However, an analytical technique that quantitates in vitro matrix
      mineralization of live cells without any labeling or complex treatments is still
      lacking. In this study, we investigate a simple and enhanced optical method based
      on surface plasmon resonance (SPR) detection that can monitor the surface-limited
      refractive index change in real-time. During monitoring MC3T3-E1 cells in vitro
      culture every 2 days for over 4 weeks, the SPR angle is shifted with a greater
      resonance change in cells cultured with osteogenic reagents than those without
      the reagents. In addition, the SPR results obtained have a close relevance with
      the tendency of conventional mineralization staining and an inductively coupled
      plasma-based calcium content measure. These results suggest a new approach of a
      real-time SPR monitoring in vitro matrix mineralization of cultured cells.

PMID- 21192004
TI  - Enzyme inactivation by ethanol and development of a kinetic model for
      thermophilic simultaneous saccharification and fermentation at 50  degrees C with
      Thermoanaerobacterium saccharolyticum ALK2.
AB  - Studies were undertaken to understand phenomena operative during simultaneous
      saccharification and fermentation (SSF) of a model cellulosic substrate (Avicel)
      at 50 degrees C with enzymatic hydrolysis mediated by a commercial cellulase
      preparation (Spezyme CP) and fermentation by a thermophilic bacterium engineered
      to produce ethanol at high yield, Thermoanaerobacterium saccharolyticum ALK2.
      Thermal inactivation at 50  degrees C, as shown by the loss of 50% of enzyme
      activity over 4 days in the absence of ethanol, was more severe than at 37 
      degrees C, where only 25% of enzyme activity was lost. In addition, at 50 
      degrees C ethanol more strongly influenced enzyme stability. Enzyme activity was
      moderately stabilized between ethanol concentrations of 0 and 40 g/L, but ethanol
      concentrations above 40 g/L accelerated enzyme inactivation, leading to 75% loss
      of enzymatic activity in 80 g/L ethanol after 4 days. At 37  degrees C, ethanol
      did not show a strong effect on the rate of enzyme inactivation. Inhibition of
      cellulase activity by ethanol, measured at both temperatures, was relatively
      similar, with the relative rate of hydrolysis inhibited 50% at ethanol
      concentrations of 56.4 and 58.7 g/L at 50 and 37  degrees C, respectively. A
      mathematical model was developed to test whether the measured phenomena were
      sufficient to quantitatively describe system behavior and was found to have good
      predictive capability at initial Avicel concentrations of 20 and 50 g/L.

PMID- 21192017
TI  - Older adults' own reasoning for their alcohol consumption.
AB  - OBJECTIVE: The aim of the study was to investigate what the older adults
      themselves consider to be the reasons for their alcohol consumption. METHODS: The
      data were collected with a postal questionnaire from a random sample of 2100
      elderly people (>=65 years) living in the medium-sized city of Espoo, Finland.
      The response rate was 71.6% from the community-dwelling sample. Altogether 868
      persons responded that they use alcohol. Of them, 831 gave reasons for their
      drinking. We defined "at-risk users" as consuming >7 drinks per week, or >=5
      drinks on a typical drinking day, or using >=3 drinks several times per week.
      RESULTS: Main reasons given for alcohol consumption were "having fun or
      celebration" (58.7%), "for social reasons" (54.2%), "using alcohol for medicinal
      purposes" (20.1%), and "with meals" (13.8%). Younger age groups reported more
      often than the older age groups that they use alcohol for "having fun or
      celebration" and "for social reasons." The older age groups used more often
      "alcohol for medicinal purposes". Men used alcohol more often than women "as
      pastime" or "as sauna drink". Those defined as "at-risk users" reported using
      alcohol because of "meaningless life," for "relieving depression," "relieving
      anxiety," and "relieving loneliness." CONCLUSIONS: Older adults have diverse
      alcohol consumption habits like people in other age groups. The oldest olds
      reported that they use alcohol for medicinal purposes. The "at-risk users" admit
      they use alcohol because of meaningless life, and relieving depression, anxiety,
      and loneliness.

PMID- 21192018
TI  - MRI-defined vascular depression: a review of the construct.
AB  - OBJECTIVE: To review the construct of MRI-defined vascular depression and to
      examine the substantive and methodological issues that bear on its validity as a
      distinct subtype of depression in late life. DESIGN: Literature review. RESULTS:
      We identified three areas that are critical to establishing the validity of MRI
      defined vascular depression: (1) understanding and delineating the relationship
      between MRI hyperintensities, executive dysfunction, and antidepressant treatment
      outcome; (2) understanding the relationship between, and establishing the
      validity of, qualitative and quantitative approaches to the measurement of MRI
      hyperintensities (the primary feature of the proposed subtype); (3) establishing
      the clinical presentation and course of the subtype in the context of other late
      life disorders. CONCLUSIONS: Despite considerable data supporting the validity of
      MRI-defined vascular depression, there are a number of critical issues that
      remain, including establishing a causal relationship between cerebrovascular
      disease and late-life depression, establishing consistent diagnostic criteria,
      determining the importance of lesion type and location, and understanding the
      course of the disorder.

PMID- 21192020
TI  - Role of 2-oxo and 2-thioxo modifications on the fragmentation reactions of the
      histidine radical cation.
AB  - The fragmentation reactions of the radical cations, M(.+), of histidine, 2-oxo
      histidine and 2-thioxo-histidine were examined using a combination of experiments
      performed on a linear ion trap and density functional theory (DFT) calculations
      at the UB3-LYP/6-311++G(d,p) level of theory. Low-energy collision-induced
      dissociation (CID) on [Cu(II)(terpy)(M)](2+) complexes, formed via electrospray
      ionisation, produced the radical cations in sufficient yield to examine their
      unimolecular chemistry via an additional stage of CID. The CID spectrum of the
      radical cation of histidine is dominated by loss of water with the next most
      abundant ion arising from the combined loss of H(2)O and CO. In contrast, the CID
      spectra of the radical cations of 2-oxo-histidine and 2-thioxo-histidine are
      dominated by the combined loss of CO(2) and NH=CH(2). The observed differences
      are rationalised via DFT calculations which reveal that the barrier associated
      with loss of CO(2) from the histidine radical cation is higher than that for loss
      of H(2)O. In contrast, the introduction of an oxygen or sulfur atom into the side
      chain of histidine results in a reversal of the order of these barrier heights,
      thus making CO(2) loss the preferred pathway.

PMID- 21192021
TI  - Properties of mouse vomeronasal receptor and assessment of its role in pheromone
      signalling.
AB  - Vomeronasal type 2 receptor (V2Rx) from Swiss mouse (Mus musculus (L.)) was
      analyzed by high-resolution ion-exchange chromatography, reversed-phase high
      performance liquid chromatography (RP-HPLC), matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), Fourier
      transform ion cyclotron resonance mass spectrometry (FTICR-MS), Ion Spray tandem
      mass spectrometry (MS/MS), 10% sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) and 1-aminoanthracene (1-AMA) fluorometric assay.
      Vomeronasal sensory neuronal cell bound proteins were resolved into major protein
      peaks. Several proteins were identified and subsequently purified as the V2Rx
      receptor on 10% SDS-PAGE with trace amounts of other protein bands. The molecular
      weight of the identified V2Rx was 109 kDa. MALDI-TOF and micro-sequencing
      experiments demonstrated that the identified V2Rx receptor shared considerable
      sequence similarity with vomeronasal receptor type 2 (NCBI Accession Number
      AB267725), which is a seven transmembrane peptide with 912 amino acid residues.
      The molecular characterization revealed that the N-terminus of the V2Rx receptor
      contained the 11GAEAAE16 domain involved in pheromone signalling. The biometric
      assay (octanamine-V2Rx binding) showed the identified V2Rx receptor and mouse sex
      pheromone to 2-octanamine (methyl heptyl) in a 1:1 ratio. Uptake of odourants
      determined in physiological condition showed enhanced V2Rx receptors as volatile
      hydrophobic pheromone receptors in the vomeronasal neuron of the Swiss mouse.

PMID- 21192022
TI  - Semiconductor cadmium sulphide nanoparticles as matrices for peptides and as co
      matrices for the analysis of large proteins in matrix-assisted laser
      desorption/ionization reflectron and linear time-of-flight mass spectrometry.
AB  - The use of semiconductor cadmium sulphide nanoparticles (CdS NPs) capped with 4
      aminothiophenol (ATP) and 11-mercaptoundecanoic acid (MUA) is described for the
      first time as matrices and as co-matrices for the analysis of peptides and
      proteins in matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF-MS). UV-visible spectroscopy, Fourier transform infrared
      (FT-IR) spectroscopy, scanning electron microscopy (SEM) and transmission
      electron microscopy (TEM) were applied for the characterization of functionalized
      CdS NPs. The synthesized CdS-ATP and CdS-MUA NPs exhibit uniform size
      distribution with diameter of 15-25 nm and 20-30 nm, respectively. The -NH(2)
      (ATP) and -COOH (MUA) groups modified on the surfaces of CdS NPs provide
      ionizable moieties for efficient transfer of protons during the
      desorption/ionization of analytes. The functionalized CdS NPs have desirable
      properties for the analysis of peptides in reflectron MALDI-TOF-MS with
      suppressed background noise and increased mass resolution (4-13-fold) in linear
      MALDI-TOF-MS. The application of CdS-MUA NPs and SA as the co-matrices in MALDI
      MS is demonstrated for the analysis of hydrophobic proteins from soybean.

PMID- 21192023
TI  - A strategy for liquid chromatography/tandem mass spectrometry based quantitation
      of pegylated protein drugs in plasma using plasma protein precipitation with
      water-miscible organic solvents and subsequent trypsin digestion to generate
      surrogate peptides for detection.
AB  - Recently, we have developed liquid chromatography/tandem mass spectrometry
      (LC/MS/MS)-based methods for the quantitation of pegylated therapeutic proteins
      in plasma. The methods are based on the LC/MS/MS detection of a surrogate peptide
      generated from trypsin digestion of the therapeutic protein. Various parameters
      related to the bioanalytical methods were evaluated and optimized, including the
      preparation of calibration standards and quality control samples, sample
      extraction, internal standard selection and its stage of addition, trypsin
      digestion, and non-specific binding. In this paper, we report the development of
      a method for a specific pegylated therapeutic protein and detail the various
      optimization steps undertaken. Simple extraction of the pegylated therapeutic
      protein from plasma was achieved via the precipitation of the endogenous proteins
      in plasma using acidic isopropanol and the resulting supernatant extract was
      subjected to trypsin digestion. A unique tryptic peptide arising from the
      pegylated therapeutic protein was used for LC/MS/MS-based detection and
      quantitation. A protein and a peptide were used as internal standards, with the
      former added before the sample extraction and the latter after the sample
      extraction. The method developed is simple, sensitive, specific and rugged, and
      has been implemented in a high throughput 96-well format to analyze plasma
      samples from in vivo studies. A required lower limit of quantitation (LLOQ) of 10
      ng/mL, expressed in terms of the concentration of the protein drug, was easily
      achieved.

PMID- 21192024
TI  - Comparison of the isomeric alpha-amino acyl adenylates and amino acid
      phosphoramidates of adenosine by electrospray ionization tandem mass
      spectrometry.
AB  - The isomeric alpha-amino acyl adenylates and amino acid phosphoramidates of
      adenosine were synthesized and analyzed in detail by electrospray ionization
      tandem mass spectrometry (ESI-MS(n)). In ESI-MS/MS of alpha-amino acyl
      adenylates, the novel rearrangement ion [cAMP-H](-) observed as the most intense
      signal was formed through the pentacoordinate phosphorus intermediate with a six
      membered ring by nucleophilic attack of the 3'-hydroxyl group on the phosphorus
      atom. In contrast, for the amino acid phosphoramidate of adenosine, the
      phosphorus atom could be attacked not only by the carboxylic group to form the
      cyclic aminoacyl phosphoramidates (CAPAs), but also by the nitrogen atom on the
      nucleobase leading to intramolecular phosphoryl group migration. It was found
      that the sodium ion having multidentate binding ability played an essential role
      in this characteristic rearrangement. The proposed mechanisms were supported by
      the MS/MS study, deuterium-labeled experiments, high-resolution tandem mass
      spectrometry and moderate calculations at the B3LYP/6-31G* level. The
      characteristic fragmentation patterns of alpha-amino acyl phosphates and amino
      acid phosphoramidates allows identification of stereoisomers when either the
      phosphorylation is at the N-terminus or C-terminus of amino acids.

PMID- 21192025
TI  - A counter-intuitive approach to calculating non-exchangeable 2H isotopic
      composition of hair: treating the molar exchange fraction fE as a process-related
      rather than compound-specific variable.
AB  - Hair is a keratinous tissue that incorporates hydrogen from material that an
      animal consumes but it is metabolically inert following synthesis. The stable
      hydrogen isotope composition of hair has been used in ecological studies to track
      migrations of mammals as well as for forensic and archaeological purposes to
      determine the provenance of human remains or the recent geographic life
      trajectory of living people. Measurement of the total hydrogen isotopic
      composition of a hair sample yields a composite value comprised of both
      metabolically informative, non-exchangeable hydrogen and exchangeable hydrogen,
      with the latter reflecting ambient or sample preparation conditions. Neither of
      these attributes is directly measurable, and the non-exchangeable hydrogen
      composition is obtained by estimation using a commonly applied mathematical
      expression incorporating sample measurements obtained from two distinct
      equilibration procedures. This commonly used approach treats the fraction of
      exchangeable hydrogen as a mixing ratio, with a minimal procedural fractionation
      factor assumed to be close or equal to 1. Instead, we propose to use full molar
      ratios to derive an expression for the non-exchangeable hydrogen composition
      explicitly as a function of both the procedural fractionation factor alpha and
      the molar hydrogen exchange fraction f(E). We apply these derivations in a
      longitudinal study of a hair sample and demonstrate that the molar hydrogen
      exchange fraction f(E) should, like the procedural fractionation factor alpha, be
      treated as a process-dependent parameter, i.e. a reaction-specific constant. This
      is a counter-intuitive notion given that maximum theoretical values for the molar
      hydrogen exchange fraction f(E) can be calculated that are arguably protein-type
      specific and, as such, f(E) could be regarded as a compound-specific constant. We
      also make some additional suggestions for future approaches to determine the non
      exchangeable hydrogen composition of hair and the use of standards.

PMID- 21192026
TI  - Single drop microextraction coupled with matrix-assisted laser
      desorption/ionization mass spectrometry for rapid and direct analysis of
      hydrophobic peptides from biological samples in high salt solution.
AB  - Single drop microextraction (SDME) coupled with matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI-MS) has been applied for direct
      analysis of hydrophobic peptides (valinomycin and gramicidin D) from biological
      samples (urine and plasma) in high salt solution. The optimal conditions such as
      selection of extraction solvent, stirring rate, extraction time, effect of salt
      concentration and matrix-to-analyte ratio were investigated. The limits of
      detection (LODs) were found to be 73 nM to 170 nM for valinomycin and 96 nM to
      5.5 uM for gramicidin D in high salt solution (1.7 M of NaCl) in MALDI-MS. The
      current approach can enhance the LODs by 11-320-fold for gramicidin D analysis in
      water, urine and plasma in high salt solution. Furthermore, the current approach
      has been successfully demonstrated for real-world sample analysis (beta-carotene
      from carrots) by MALDI-MS. The current approach is a rapid, simple and efficient
      clean-up platform for direct analysis of hydrophobic molecules in biological
      samples from high salt solution.

PMID- 21192027
TI  - Liquid chromatography/tandem mass spectrometry analysis of long-chain oxidation
      products of cardiolipin induced by the hydroxyl radical.
AB  - The anionic phospholipid cardiolipin (CL) is found almost exclusively in the
      inner membrane of mitochondria, playing an important role in energy metabolism.
      Oxidation of CL has been associated with apoptotic events and various
      pathologies. In this study, electrospray ionization mass spectrometry coupled
      with liquid chromatography (LC/ESI-MS) was used to identify tetralinoleoyl
      cardiolipin (TLCL) modifications induced by the OH(.) radical generated under
      Fenton reaction conditions (H(2)O(2) and Fe(2+)). The identified oxidation
      products of TLCL contained 2, 4, 6 and 8 additional oxygen atoms. These long
      chain oxidation products were characterized by LC/ESI-MS/MS as doubly [M-2H](2-)
      and singly charged [M-H](-) ions. A detailed analysis of the fragmentation
      pathways of these precursor ions allowed the identification of hydroperoxy
      derivatives of CL. MS/MS analysis indicated that CL oxidation products with 4, 6
      and 8 oxygen atoms have one fatty acyl chain bearing 4 oxygen atoms ([RCOO+4O](
      )). Even when the TLCL molecule was oxidized by the addition of eight oxygen
      atoms, one of the acyl chains remained non-modified and one fatty acyl chain
      contained three or four oxygen atoms. This led us to conclude that under
      oxidative conditions by the OH(.) radical, the distribution of oxygens/peroxy
      groups in the CL molecule is not random, even when CL has the same fatty acyl
      chains in all the positions. Using mass spectrometry, the oxidation products have
      been unequivocally assigned, which may be useful for their detection in
      biological samples.

PMID- 21192028
TI  - Strategy for identification and detection of multiple oxidative modifications
      within proteins applied on persulfate-oxidized hemoglobin and human serum
      albumin.
AB  - Oxidative stress has been suggested as an underlying mechanism of many human
      diseases. However, definitive evidence for this association has not been
      presented due to different shortcomings of the methods used to measure biomarkers
      of oxidative stress. Persulfates are oxidizing agents known to elicit
      hypersensitive reactions from the airways and skin. Despite a frequent use of
      persulfates at many work places, no biomarkers for persulfate exposure are
      available. The aim of this study was to develop a strategy for the identification
      and detection of multiple oxidative modifications within proteins. This strategy
      was applied on persulfate-oxidized proteins to identify oxidized peptides
      suitable for further investigation as biomarkers of persulfate exposure or
      oxidative stress. A strategy for the identification and the relative
      quantification of multiple oxidative modifications within proteins was developed.
      The usage of two software packages facilitated the search for modified peptides
      to a great extent. Oxidized peptides were relatively quantified using liquid
      chromatography/tandem mass spectrometry in selected reaction monitoring mode. The
      result showed that persulfates oxidize tryptophans and methionines resulting in
      mass shifts of 16 and/or 32 Da. Also, oxidized albumin peptides in nasal lavage
      fluid samples from subjects challenged with persulfate were detected. The
      oxidation degree before and after challenge remained constant for peptides
      containing methionine sulfoxide. For peptides containing oxidized tryptophan the
      oxidation degree increased after exposure. Some of these oxidized peptides may be
      suitable as biomarkers; however, further evaluation is required.

PMID- 21192029
TI  - Identification of carbadox metabolites formed by liver microsomes from rats, pigs
      and chickens using high-performance liquid chromatography combined with hybrid
      ion trap/time-of-flight mass spectrometry.
AB  - Carbadox (methyl-3-(2-quinoxalinylmethylene)-carbazate-N(1),N(4)-dioxide) is a
      chemotherapeutic growth promoter added to feed for starter pigs. In this work,
      the metabolism of carbadox in rat, pig and chicken liver microsomes has been
      studied firstly. The incubation mixtures were then processed and analyzed for
      metabolites with a sensitive and reliable method based on high-performance liquid
      chromatography combined with hybrid ion trap/time-of-flight mass spectrometry
      (LC/MS-IT-TOF). With the help of chromatographic behavior and accurate mass
      measurements, it is possible to rapidly and reliably characterize the metabolites
      of carbadox. The structural elucidations of these metabolites were performed by
      comparing the changes in the accurate molecular masses and fragment ions
      generated from precursor ions with those of parent drug. The present results
      showed that the metabolism of carbadox in liver microsomes had qualitative
      species-difference. A total of seven metabolites were identified in rat liver
      microsomes. Five metabolites (Cb1-Cb3, Cb5, Cb7) were observed in pig and chicken
      liver microsomes. In addition, metabolite Cb6 was also detected in chicken liver
      microsomes. The peak areas of the metabolites in the three species are different.
      For the formations of Cb1, Cb2, Cb5 and Cb6, the rank order was rat>chicken>pig;
      Cb3; pig~chicken>rat. Cb1, Cb2 and Cb3 have been previously reported, whereas the
      other four metabolites were novel. The N->O group reduction and hydroxylation
      followed by N->O group reduction were the main metabolic pathways for carbadox in
      the three species.

PMID- 21192030
TI  - Fragmentation patterns of novel dithiocarbamate derivatives with pharmaceutical
      activity under electrospray ionization tandem mass spectrometry conditions.
AB  - The fragmentation patterns of a novel series of dithiocarbamate derivatives with
      pharmaceutical activity were investigated by positive ion electrospray ionization
      mass spectrometry in conjunction with tandem mass spectrometry (ESI-MS(n)). In
      the gas phase, the dithiocarbamate protonated molecules containing the
      piperazinium moiety undergo losses of bromide to form the piperazinium cation by
      ionization, followed by subsequent losses of methyl bromide, ring opening and
      rearrangement of piperazinium. Furthermore, the dithiocarbamate derivatives and
      their intermediates both undergo cleavage of the C-S bond to produce two common
      fragment ions. The different fragmentation observed for these compounds
      facilitated their identification and could be valuable in the further study of
      their metabolic pathways as prodrugs.

PMID- 21192032
TI  - Electrospray ionization mass spectrometric fragmentation of hydroquinone
      derivatives.
AB  - The fragmentation patterns of nine di-, tri- and tetracyclic hydroquinones with
      potential antitumor activity were rationalized by invoking competing mechanisms
      that included sterically accelerated homolytic cleavage, Meerwein-type
      rearrangements and dehydrations through elimination or intramolecular
      nucleophilic substitution.

PMID- 21192031
TI  - Building an empirical mass spectra library for screening of organic pollutants by
      ultra-high-pressure liquid chromatography/hybrid quadrupole time-of-flight mass
      spectrometry.
AB  - Hybrid quadrupole time-of-flight mass spectrometry (QTOF MS) has gained wide
      acceptance in many fields of chemistry, for example, proteomics, metabolomics and
      small molecule analysis. This has been due to the numerous technological advances
      made to this mass analyser in recent years. In the environmental field, the
      instrument has proven to be one of the most powerful approaches for the screening
      of organic pollutants in different matrices due to its high sensitivity in full
      acquisition mode and mass accuracy measurements. In the work presented here, the
      optimum experimental conditions for the creation of an empirical TOF MS spectra
      library have been evaluated. For this model we have used a QTOF Premier mass
      spectrometer and investigated its functionalities to obtain the best MS data,
      mainly in terms of mass accuracy, dynamic range and sensitivity. Different
      parameters that can affect mass accuracy, such as lock mass, ion abundance,
      spectral resolution, instrument calibration or matrix effect, have also been
      carefully evaluated using test compounds (mainly pesticides and antibiotics). The
      role of ultra-high-pressure liquid chromatography (UHPLC), especially when
      dealing with complex matrices, has also been tested. In addition to the mass
      accuracy measurements, this analyser allows the simultaneous acquisition of low
      and high collision energy spectra. This acquisition mode greatly enhances the
      reliable identification of detected compounds due to the useful (de)protonated
      molecule and fragment ion accurate mass information obtained when working in this
      mode. An in-house empirical spectral library was built for approximately 230
      organic pollutants making use of QTOF MS in MS(E) mode. All the information
      reported in this paper is made available to the readers to facilitate screening
      and identification of relevant organic pollutants by QTOF MS.

PMID- 21192033
TI  - Hydrophilic interaction liquid chromatography/tandem mass spectrometry for the
      analysis of diallyldimethylammonium chloride in water.
AB  - We report a selective, sensitive and fast liquid chromatography/tandem mass
      spectrometry (LC/MS/MS) method for the determination of diallyldimethylammonium
      chloride (DADMAC) in water. Hydrophilic interaction liquid chromatography (HILIC)
      was used to avoid ion-pairing reagents, which are generally employed to retain
      cationic compounds. The complementary information obtained in a triple quadrupole
      mass spectrometer and in an ion trap Orbitrap has been used to study the
      fragmentation of the DADMAC cation [M](+) and for the correct assignment of the
      products ions. The HILIC/MS/MS method developed, using electrospray ionization in
      positive ion mode and selected reaction monitoring (SRM) acquisition mode, led to
      a reliable determination and confirmation of the DADMAC cation in water samples
      down to 50 ng L(-1). The low detection limit achieved, in combination with the
      absence of matrix effects, allowed the direct analysis of samples without any
      pretreatment, preconcentration or clean-up step. DADMAC was determined in samples
      collected in a drinking water treatment plant (DWTP) in Barcelona (Spain) and it
      was found in the influent at the ug L(-1) level.

PMID- 21192034
TI  - Gas chromatography/mass spectrometry determination of mephedrone in drug seizures
      after derivatization with 2,2,2-trichloroethyl chloroformate.

PMID- 21192035
TI  - Evaluation of methionine sulphoxide content of ApoA-I in type 2 diabetic patients
      and young coronaropathic subjects: a preliminary study.

PMID- 21192060
TI  - Association of the highly prevalent TP53 R337H mutation with pediatric choroid
      plexus carcinoma and osteosarcoma in southeast Brazil.
AB  - BACKGROUND: The inherited, low-penetrance arginine-to-histidine substitution at
      codon 337 (R337H) of the tumor protein 53 gene (TP53) is clustered in southeast
      Brazil (estimated frequency, 0.3%). Although its tumorigenic effect initially
      appeared to be tissue-specific, recent evidence suggests its association with a
      broader range of tumors. Therefore, the authors of this report investigated the
      spectrum of pediatric malignancies associated with the TP53 R337H mutation at a
      single referral institution in southeast Brazil. METHODS: Genomic DNA samples
      from 493 children with malignancies were screened for the R337H mutation.
      Available tumor samples from carriers were investigated for loss of
      heterozygosity (LOH) and nuclear p53 accumulation. Clinical data were obtained
      from medical records. RESULTS: Sixty-five of 70 patients (93%) with
      adrenocortical tumors (ACTs), 9 of 13 patients (69%) with choroid plexus
      carcinoma (CPC), and 3 of 41 patients (7.3%) with osteosarcoma carried the
      mutation. The proportion of CPC to choroid plexus papilloma (CPP) was much higher
      than that reported elsewhere. Osteosarcoma in carriers had a significantly poorer
      outcome (P = .02). The mutation was not identified in patients who had acute
      lymphoblastic leukemia (ALL) (n = 187), recurrent ALL (n = 49), acute myeloid
      leukemia (n = 44), lymphoma (n = 30), non-CPC central nervous system tumors (n =
      26), Ewing sarcoma (n = 25), or rhabdomyosarcoma (n = 8). Among the tumors that
      were available for analysis, LOH with retention of the mutant allele was
      confirmed in 21 of 21 ACTs, in 2 of 2 CPCs, and in 2 of 3 osteosarcomas that were
      positive for R337H. CPCs and osteosarcomas that were positive for R337H had
      marked nuclear accumulation of p53. CONCLUSIONS: The current findings
      demonstrated compellingly that the TP53 R337H mutation is associated not only
      with ACT but also with CPC and, to a lesser extent, with osteosarcoma, both of
      which are core-component tumors of the Li-Fraumeni syndrome.

PMID- 21192075
TI  - Interconnected cortical networks between primary somatosensory cortex septal
      columns and posterior parietal cortex in rat.
AB  - Visual and somesthetic cues are used for spatial processing in the posterior
      parietal cortex (PPC) of the mammalian brain. In rats, somatic information
      collected by the mystacial whiskers is critically involved in constructing a
      neural representation of the external space. Here, we delineated the topography
      of the cortical pathway from the primary somatosensory cortex (SI) that may
      deliver vibrissal cues to PPC for spatial processing. For anterograde tracing, we
      made small injections of biotinylated dextran amine (BDA) into SI barrel cortex.
      The injections in the regions directly above the septal compartments produced
      dense terminals in PPC, whereas injections above the center of the barrels
      resulted in sparse terminals. For retrograde tracing, we made large injections of
      cholera toxin subunit B (CtB) in PPC. Retrogradely labeled neurons within SI
      barrel cortex formed multiple, parallel strips. In layer IV, these strips of
      labeled neurons were confined within the septal rows, extending from barrel arc
      position 0 to 5. In the extragranular layers, labeled neurons were clustered
      primarily within the vertical extensions of the septal rows and extended to the
      edges of neighboring barrel columns. Based on these findings, in which SI
      projections to PPC arise mainly from the septal columns, we hypothesize that
      septal columns may form interconnected cortical networks that engage in spatial
      information processing contingent on somestheic cues.

PMID- 21192069
TI  - Trauma-induced alterations in cognition and Arc expression are reduced by
      previous exposure to 56Fe irradiation.
AB  - Exposure to ionizing irradiation may affect brain functions directly, but may
      also change tissue sensitivity to a secondary insult such as trauma, stroke, or
      degenerative disease. To determine if a low dose of particulate irradiation
      sensitizes the brain to a subsequent injury, C56BL6 mice were exposed to brain
      only irradiation with 0.5 Gy of (56) Fe ions. Two months later, unilateral
      traumatic brain injury was induced using a controlled cortical impact system.
      Three weeks after trauma, animals received multiple BrdU injections and 30 days
      later were tested for cognitive performance in the Morris water maze. All animals
      were able to locate the visible and hidden platform during training; however,
      treatment effects were seen when spatial memory retention was assessed in the
      probe trial (no platform). Although sham and irradiated animals showed spatial
      memory retention, mice that received trauma alone did not. When trauma was
      preceded by irradiation, performance in the water maze was not different from
      sham-treated animals, suggesting that low-dose irradiation had a protective
      effect in the context of a subsequent traumatic injury. Measures of hippocampal
      neurogenesis showed that combined injury did not induce any changes greater that
      those seen after trauma or radiation alone. After trauma, there was a significant
      decrease in the percentage of neurons expressing the behaviorally induced
      immediate early gene Arc in both hemispheres, without associated neuronal loss.
      After combined injury there were no differences relative to sham-treated mice.
      Our results suggest that combined injury resulted in decreased alterations of our
      endpoints compared to trauma alone. Although the underlying mechanisms are not
      yet known, these results resemble a preconditioning, adaptive, or inducible-like
      protective response, where a sublethal or potentially injurious stimulus (i.e.,
      irradiation) induces tolerance to a subsequent and potentially more damaging
      insult (trauma).

PMID- 21192077
TI  - Subcellular distribution of connexin45 in OFF bipolar cells of the mouse retina.
AB  - In the mouse retina, connexin45 (Cx45) participates in the gap junction between
      ON cone bipolar cells and AII amacrine cells, which constitutes an essential
      element of the primary rod pathway. Although it has been shown that Cx45 is also
      expressed in OFF bipolar cells, its subcellular localization and functional role
      in these cells are unknown. Here, we analyzed the localization of Cx45 on OFF
      bipolar cells in the mouse retina. For this, we used wild-type mice and a
      transgenic mouse line that expressed, in addition to native Cx45, a fusion
      protein consisting of Cx45 and the enhanced green fluorescent protein (EGFP).
      Cx45-EGFP expression generates an EGFP signal at gap junctions containing Cx45.
      Combining immunohistochemistry with intracellular injections, we found that Cx45
      was present on dendrites and axon terminals of all OFF bipolar cell types. Cx45
      was not found at intersections of two terminal processes of the same type,
      suggesting that Cx45 might not form gap junctions between axon terminals of the
      same OFF bipolar cell type but rather might connect OFF bipolar cells to amacrine
      or ganglion cells. In OFF bipolar cell dendrites, Cx45 was found predominantly in
      the proximal outer plexiform layer (OPL), well below the cone pedicles. Cx45 did
      not colocalize with Cx36, which is found predominantly in the distal OPL. We
      conclude that Cx45 is expressed on OFF bipolar cell dendrites, presumably forming
      gap junctions with cells of the same type, and on OFF bipolar cell axon
      terminals, presumably forming heterologous gap junctions with other retinal
      neurons.

PMID- 21192076
TI  - Serotonin receptor diversity in the human colon: Expression of serotonin type 3
      receptor subunits 5-HT3C, 5-HT3D, and 5-HT3E.
AB  - Since the first description of 5-HT3 receptors more than 50 years ago, there has
      been speculation about the molecular basis of their receptor heterogeneity. We
      have cloned the genes encoding novel 5-HT3 subunits 5-HT3C, 5-HT3D, and 5-HT3E
      and have shown that these subunits are able to form functional heteromeric
      receptors when coexpressed with the 5-HT3A subunit. However, whether these
      subunits are actually expressed in human tissue remained to be confirmed. In the
      current study, we performed immunocytochemistry to locate the 5-HT3A as well as
      the 5-HT3C, 5-HT3D, and 5-HT3E subunits within the human colon. Western blot
      analysis was used to confirm subunit expression, and RT-PCR was employed to
      detect transcripts encoding 5-HT3 receptor subunits in microdissected tissue
      samples. This investigation revealed, for the first time, that 5-HT3C, 5-HT3D,
      and 5-HT3E subunits are coexpressed with 5-HT3A in cell bodies of myenteric
      neurons. Furthermore, 5-HT3A and 5-HT3D were found to be expressed in submucosal
      plexus of the human large intestine. These data provide a strong basis for future
      studies of the roles that specific 5-HT3 receptor subtypes play in the function
      of the enteric and central nervous systems and the contribution that specific 5
      HT3 receptors make to the pathophysiology of gastrointestinal disorders such as
      irritable bowel syndrome and dyspepsia.

PMID- 21192078
TI  - Decline in adult neurogenesis during aging follows a topographic pattern in the
      mouse hippocampus.
AB  - In the rodent brain, diverse functions are topographically distributed within the
      hippocampus. For instance, the dorsal (septal) hippocampus is involved in spatial
      memory, whereas the ventral (temporal) hippocampus is related to emotion and
      anxiety. Accumulating evidence shows that age-dependent decline in hippocampal
      neurogenesis is associated with impairments of these functions. However, little
      is known about whether the decline in dentate granule cell production during
      aging follows a topographic pattern. Here we quantitatively estimated specific
      populations of adult-born cells in young adult and middle-aged mice by using
      endogenous markers and determined whether age-dependent reductions in adult
      neurogenesis exhibited topographic differences. The numerical densities (NDs) of
      putative primary progenitors, intermediate neuronal progenitors, and neuronal
      lineages were higher in the dorsal dentate gyrus (DG) than in the ventral DG both
      in young adult and in middle-aged mice, but the ratios of the NDs in the dorsal
      DG to the NDs in the ventral DG noticeably increased with age. The age-related
      reductions in the numbers of these populations were larger in the ventral DG than
      in the dorsal DG. By contrast, the NDs of glial lineages were higher in the
      ventral DG than in the dorsal DG during life, and the numbers of glial lineages
      showed no significant age-related changes. Our findings suggest that
      neurogenesis, but not gliogenesis, wanes faster in the ventral hippocampus than
      in the dorsal hippocampus during aging. Such age-related topographic changes in
      hippocampal neurogenesis might be implicated in memory and affective impairments
      in older people.

PMID- 21192079
TI  - Cell-type-specific localization of protocadherin beta16 at AMPA and AMPA/Kainate
      receptor-containing synapses in the primate retina.
AB  - Protocadherins (Pcdhs) are thought to be key features of cell-type-specific
      synapse formation. Here we analyzed the expression pattern of Pcdh subunit beta16
      (beta16) in the primate retina by applying antibodies against beta16, different
      subunits of ionotropic glutamate receptors (GluRs), and cell-type-specific
      markers as well as by coimmunoprecipitation and Western blots. Immunocytochemical
      localization was analyzed by confocal microscopy and preembedding electron
      microscopy. In the outer plexiform layer (OPL) H1, but not H2, horizontal cells
      expressed beta16 as revealed by the strong reduction of beta16 at short
      wavelength-sensitive cones. beta16 colocalized with the GluR subunits GluR2-4 at
      horizontal cell dendritic tips and with GluR2-4 and GluR6/7 at the desmosome-like
      junctions. At the latter, these AMPA and kainate receptor subunits were found to
      be clustered within single synaptic hot spots. Additionally, beta16-labeled
      dendritic tips of OFF cone bipolar cells appeared in triad-associated positions
      at the cone pedicle base, pointing to beta16 expression by OFF midget or DB3
      bipolar cells. In the inner plexiform layer, beta16 was localized also
      postsynaptically at most of the glutamatergic synapses. Overall, we provide
      evidence for a cell-type-specific localization of beta16 together with GluRs at
      defined postsynaptic sites and a coexistence of AMPA and kainate receptors within
      single synaptic hot spots. This study supports the hypothesis that beta16 plays
      an important role in the formation and/or stabilization of specific glutamatergic
      synapses, whereas our in vivo protein biochemical results argue against the
      existence of protein complexes formed by beta16 and GluRs.

PMID- 21192080
TI  - Spatiotemporal nuclear factor interleukin-6 expression in the rat brain during
      lipopolysaccharide-induced fever is linked to sustained hypothalamic inflammatory
      target gene induction.
AB  - Rats injected with lipopolysaccharide (LPS) show brain-controlled sickness
      symptoms, including fever. In these animals, early genomic activation of brain
      cells was previously monitored by immunohistochemical detection of transcription
      factors such as nuclear factor (NF)-kappaB or signal transducer and activator of
      transcription (STAT)3 and was linked to the initiation or maintenance of the
      febrile response. To investigate whether NF-IL6 might be another important
      transcription factor implicated in this kind of immune-to-brain signaling, rats
      were injected with LPS (100 MUg/kg, intraperitoneally) or phosphate-buffered
      saline, and brains were analyzed by immunohistochemistry, real-time PCR, or
      Western blot 4, 6, 8, and 10 hours later. Moderate to strong LPS-induced nuclear
      NF-IL6 immunoreactivity (IR) occurred in a time-dependent manner within
      circumventricular organs, namely, the vascular organ of the lamina terminalis,
      the subfornical organ, the area postrema, and the median eminence, brain
      structures with a leaky blood-brain barrier. Furthermore, nuclear NF-IL6-IR was
      observed in the pituitary gland, the choroid plexus, and the meninges as well as
      blood vessels throughout the entire brain. Endothelial, microglial, and ependymal
      cells, astrocytes, perivascular macrophages, and neurons exhibited LPS-induced
      nuclear NF-IL6-IR; mRNA levels of NF-IL6, responsive inflammatory genes, and NF
      IL6 protein levels were significantly elevated. As opposed to observations on
      STAT3 or NFkappaB, the percentage of NF-IL6-reactive cells increased in parallel
      to late phases of the febrile response. In conclusion, these results suggest a
      potential role for NF-IL6 in the maintenance or possibly the termination of LPS
      induced fever. Moreover, we propose NF-IL6 to be a delayed brain cell activation
      marker.

PMID- 21192081
TI  - Characterization of retinal function and glial cell response in a mouse model of
      oxygen-induced retinopathy.
AB  - Retinal neovascularization, such as that occurring in proliferative diabetic
      retinopathy and retinopathy of prematurity, can have serious effects on visual
      function. By using a mouse model of neovascularization, oxygen-induced
      retinopathy (OIR), the interplay among angiogenesis, neuronal function, and the
      macro- and micro-glial response was explored. OIR was induced by exposure of mice
      to 75% oxygen from postnatal day 7 (P7) to P11 and then room air until P18.
      Controls were reared in room air. Blood vessel development was assessed by using
      fluorescence histochemistry. Aberrant intravitreal neovascularization was present
      across all eccentricities of retina in mice with OIR, whereas the number of
      vessels present in the deep plexus was reduced in the central regions. Neuronal
      function of both the rod and cone pathways, assessed by using the
      electroretinogram, was found to be significantly reduced in OIR. This may in part
      be explained by an alteration in photoreceptor outer segment morphology and also
      a loss of neurons and their synapses in the inner nuclear and plexiform layers of
      the central retina. In addition, there was an increase in the number of gliotic
      Muller cells and microglia in mice with OIR and the increase in the number of
      these cells correlated with the absence of the deep plexus. This indicates that
      the activity of both macro- and microglia is altered in regions where the deep
      plexus blood supply is deficient. Treatments or genetic manipulations directed
      toward amelioration of proliferative retinopathy need to address not only the
      vascular changes but also the alterations in neuronal and macro- and microglial
      function.

PMID- 21192082
TI  - Dynamic spatiotemporal gene expression in embryonic mouse thalamus.
AB  - The anatomy of the mammalian thalamus is characterized by nuclei, which can be
      readily identified in postnatal animals. However, the molecular mechanisms that
      guide specification and differentiation of neurons in specific thalamic nuclei
      are still largely unknown, and few molecular markers are available for most of
      these thalamic subregions at early stages of development. We therefore searched
      for patterned gene expression restricted to specific mouse thalamic regions by in
      situ hybridization during the onset of thalamic neurogenesis (embryonic [E] days
      E10.5-E12.5). To obtain correct regional information, we used Shh as a landmark
      and compared spatial relationships with the zona limitans intrathalamica (Zli),
      the border of the p2 and p3 compartments of the diencephalon. We identified genes
      that are expressed specifically in the ventricular zone of the thalamic
      neuroepithelium and also identified a number of genes that already exhibited
      regional identity at E12.5. Although many genes expressed in the mantle regions
      of the thalamus at E12.5 showed regionally restricted patterns, none of these
      clearly corresponded to individual thalamic nuclei. We next examined gene
      expression at E15.5, when thalamocortical axons (TCAs) project from distinct
      regions of the thalamus and reach their targets in the cerebral cortex.
      Regionally restricted patterns of gene expression were again seen for many genes,
      but some regionally bounded expression patterns in the early postnatal thalamus
      had shifted substantially by E15.5. These findings reveal that nucleogenesis in
      the developing thalamus is associated with selective and complex changes in gene
      expression and provide a list of genes that may actively regulate the development
      of thalamic nuclei.

PMID- 21192083
TI  - Region-specific gene expression in early postnatal mouse thalamus.
AB  - Previous studies in the developing mouse thalamus have demonstrated that regional
      identity is established during early stages of development (Suzuki-Hirano et al.
      J. Comp. Neurol. 2011;519:528-543). However, the developing thalamus often shows
      little resemblance to the anatomical organization of the postnatal thalamus,
      making it difficult to identify genes that might mediate the organization of
      thalamic nuclei. We therefore analyzed the expression pattern of genes that we
      have identified as showing regional expression in embryonic thalamus on postnatal
      days (P) 6-8 by using in situ hybridization. We also identified several genes
      expressed only in the postnatal thalamus with restricted expression in specific
      nuclei. We first demonstrated the selective expression of neurotransmitter
      related genes (vGlut2, vGAT, D2R, and HTR2C), identifying the neurotransmitter
      subtypes of cells in this region, and we also demonstrated selective expression
      of additional genes in the thalamus (Steel, Slitrk6, and AI852580). In addition,
      we demonstrated expression of genes specific to somatosensory thalamic nuclei,
      the ventrobasal posterior nuclei (VP); a visual thalamic nucleus, the dorsal
      lateral geniculate nucleus (dLGN); and an auditory thalamic nucleus, the medial
      geniculate body (MGB) (p57Kip, Nr1d1, and GFRalpha1). We also identified genes
      that are selectively expressed in multiple different nuclei (Foxp2, Chst2, and
      EphA8). Finally, we demonstrated that several bone morphogenetic proteins (BMPs)
      and their inhibitors are expressed in the postnatal thalamus in a nucleus
      specific fashion, suggesting that BMPs play roles in the postnatal thalamus
      unrelated to their known role in developmental patterning. Our findings provide
      important information for understanding the mechanisms of nuclear specification
      and connectivity during development, as well as their maintenance in adult
      thalamus.

PMID- 21192084
TI  - A novel form of pigment-dispersing hormone in the central nervous system of the
      intertidal marine isopod, Eurydice pulchra (leach).
AB  - Pigment-dispersing factor (PDF) is well known as a circadian clock output factor,
      which drives daily activity rhythms in many insects. The role of its homologue,
      pigment-dispersing hormone (PDH), in the regulation of circadian and/or
      circatidal rhythmicity in crustaceans is, however, poorly understood. The
      intertidal isopod crustacean, Eurydice pulchra has well-defined circatidal (12.4
      hour) activity rhythms. In this study we show that this runs parallel to a
      circadian (24-hour) cycle of chromatophore dispersion. As a first step in
      determining the potential role of PDH in these rhythms, we have identified a
      novel form of PDH expressed in this species. Because conventional homology
      cloning was unsuccessful, we employed immuno-identification and Edman
      microsequencing to determine the primary structure of this peptide. From this,
      cDNA cloning identified the nucleotide encoding sequence and thus facilitated
      description of PDH neurons by in situ hybridization and immunohistochemistry. We
      show them to be morphologically similar to those that co-ordinate circadian
      activity rhythms in insects. In animals expressing both tidal (activity) and
      circadian (chromatophore) rhythms, however, there was no evidence for a
      corresponding periodicity in the expression of pdh transcript, as determined by
      quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in
      Eurydice heads. It is therefore suggested that any role for PDH in daily/tidal
      timing in Eurydice is not mediated at the transcriptional level, rather rhythms
      in neurohemal release may be important in such co-ordination.

PMID- 21192085
TI  - Differential expression of dopaminergic cell markers in the adult zebrafish
      forebrain.
AB  - Although the simultaneous presence of tyrosine hydroxylase (TH), aromatic amino
      acid decarboxylase (AADC), dopamine transporter (DAT), and vesicular monoamine
      transporter 2 (VMAT2) is considered as a phenotypic signature of dopamine (DA)
      neurons, it has been suggested that they are not uniformly expressed in all
      dopaminergic brain nuclei. Moreover, in nonmammalian vertebrates, two tyrosine
      hydroxylase genes (TH1 and TH2) are found, and they exhibit different expression
      patterns in zebrafish brains. Here we present a detailed description of the
      distribution of TH1, TH2, AADC, DAT, and VMAT2 transcripts, in relation to TH and
      DA immunoreactivity to better characterize dopaminergic nuclei in the adult
      zebrafish forebrain. TH2-positive cells in the hypothalamus are strongly DA
      immunoreactive (DAir), providing direct evidence that they are dopaminergic. DAir
      cells are also found in most TH1-positive or TH-immunoreactive (THir) nuclei.
      However, the DAir signal was weaker than THir in the olfactory bulb,
      telencephalon, ventral thalamus, pretectum, and some posterior tubercular and
      preoptic nuclei. These cell populations also exhibited low levels of VMAT2
      transcripts, suggesting that low DA is due to a lower vesicular DA accumulation.
      In contrast, cell populations with low levels of AADC did not always have low
      levels of DA. DAT transcripts were abundantly expressed in most of the TH1- or
      TH2-positive territories. In addition, DAT and/or VMAT2 transcripts were found in
      some periventricular cell populations such as in the telencephalon without TH1 or
      TH2 expression. Thus, expression patterns of dopaminergic cell markers are not
      homogeneous, suggesting that the gene regulatory logic determining the
      dopaminergic phenotype is unexpectedly complex.

PMID- 21192086
TI  - MRI of inducible P-selectin expression in human activated platelets involved in
      the early stages of atherosclerosis.
AB  - The noninvasive imaging of atherosclerotic plaques at an early stage of
      atherogenesis remains a major challenge for the evaluation of the pathologic
      state of patients at high risk of acute coronary syndromes. Recent studies have
      emphasized the importance of platelet-endothelial cell interactions in
      atherosclerosis-prone arteries at early stages, and the prominent role of P
      selectin in the initial loose contact between platelets and diseased vessel
      walls. A specific MR contrast agent was developed here for the targeting, with
      high affinity, of P-selectin expressed in large amounts on activated platelets
      and endothelial cells. For this purpose, PEGylated dextran/iron oxide
      nanoparticles [PEG, poly(ethylene glycol)], named versatile ultrasmall
      superparamagnetic iron oxide (VUSPIO) particles, labeled with rhodamine were
      coupled to an anti-human P-selectin antibody (VH10). Flow cytometry and
      microscopy experiments on human activated platelets were highly correlated with
      MRI (performed at 4.7 and 0.2 T), with a 50% signal decrease in T(2) and T(1)
      values corresponding to the strong labeling of activated vs resting platelets.
      The number of 1000 VH10-VUSPIO nanoparticles attained per activated platelet
      appeared to be optimal for the detection of hypo- and hyper-signals in the
      platelet pellet on T(2) - and T(1) -weighted MRI. Furthermore, in vivo imaging of
      atherosclerotic plaques in ApoE mice at 4.7 T showed a spatial resolution adapted
      to the imaging of intimal thickening and a hypo-signal at 4.7 T, as a result of
      the accumulation of VH10-VUSPIO nanoparticles in the plaque. Our work provides
      support for the further assessment of the use of VH10-VUSPIO nanoparticles as a
      promising imaging modality able to identify the early stages of atherosclerosis
      with regard to the pertinence of both the target and the antibody-conjugated
      contrast agent used.

PMID- 21192102
TI  - Isoelectric focusing of small non-covalent metal species from plants.
AB  - IEF is known as a powerful electrophoretic separation technique for amphoteric
      molecules, in particular for proteins. The objective of the present work is to
      prove the suitability of IEF also for the separation of small, non-covalent metal
      species. Investigations are performed with copper-glutathione complexes, with the
      synthetic ligand ethylenediamine-N,N'-bis(o-hydroxyphenyl)acetic acid (EDDHA) and
      respective metal complexes (Fe, Ga, Al, Ni, Zn), and with the phytosiderophore 2'
      deoxymugineic acid (DMA) and its ferric complex. It is shown that ethylenediamine
      N,N'-bis(o-hydroxyphenyl)acetic acid and DMA species are stable during
      preparative scale IEF, whereas copper-glutathione dissociates considerably. It is
      also shown that preparative scale IEF can be applied successfully to isolate
      ferric DMA from real plant samples, and that multidimensional separations are
      possible by combining preparative scale IEF with subsequent HPLC-MS analysis.
      Focusing of free ligands and respective metal complexes with di- and trivalent
      metals results in different pIs, but CIEF is usually needed for a reliable
      estimation of pI values. Limitations of the proposed methods (preparative IEF and
      CIEF) and consequences of the results with respect to metal speciation in plants
      are discussed.

PMID- 21192095
TI  - Glutamate and the biology of gliomas.
AB  - Several important and previously unrecognized roles for the neurotransmitter
      glutamate in the biology of primary brain tumors have recently been elucidated.
      Glutamate is produced and released from glioma cells via the system x(c) (-)
      cystine glutamate transporter as a byproduct of glutathione synthesis. Glutamate
      appears to play a central role in the malignant phenotype of glioma via multiple
      mechanisms. By binding to peritumoral neuronal glutamate receptors, glutamate is
      responsible for seizure induction and similarly causes excitotoxicity, which aids
      the expansion of tumor cells into the space vacated by destroyed tissue.
      Glutamate also activates ionotropic and metabotropic glutamate receptors on
      glioma cells in a paracrine and autocrine manner. alpha-Amino-3-hydroxy-5-methyl
      4-isoaxazolepropionate acid (AMPA) glutamate receptors lack the GluR2 subunit
      rendering them Ca(2+) permeable and capable of activating the AKT and MAPK
      pathways. Furthermore, these receptors are critical in aiding the invasion of
      glioma cells into normal brain. AMPA-Rs accumulate at focal adhesion sites where
      they may indirectly mediate interactions between the extracellular matrix and
      integrins. Glutamate receptor stimulation results in activation of focal adhesion
      kinase, which is critical to the regulation of growth factor and integrin
      stimulated cell motility and invasion. The multitude of effects of glutamate on
      glioma biology supports the rationale for pharmacological targeting of glutamate
      receptors and transporters. Several ongoing and recently completed clinical
      trials are exploring the therapeutic potential of interrupting glutamate-mediated
      brain tumor growth.

PMID- 21192105
TI  - Highly efficient reinforcement of poly-L-lactide materials by polymer blending of
      a thermotropic liquid crystalline polymer.
AB  - A novel polymer blend system consisting of poly(l-lactide) (PLLA) and a
      thermotropic liquid crystalline polymer (LCP: an aromatic polyester comprising
      poly(4-hydroxybenzoate) sequences) was investigated in the presence and absence
      of a polycabodiimide (PCD). Scanning electron micrographs of the injection-molded
      polymer blends revealed the formation of fibrous structure of LCP in the PLLA
      matrix, supporting the efficient toughening. In particular, the LCP fibrils
      became semimicrometer in diameter in the presence of PCD with which both PLLA and
      LCP had reacted during the melt blending to form their block and graft copolymers
      working as compatibilizer. The blend specimens containing LCP in 20-30 wt % were
      found to hold high dynamic storage-moduli (E') at high temperature. In addition,
      the E' value of the specimens containing 30 wt % of LCP reached 10.7 GPa at room
      temperature, being significantly higher than that of PLLA.

PMID- 21192106
TI  - Correlation to estimate emission rates for soil-applied fumigants.
AB  - The emission rates [ER (MUg m-2 s-1)] for subsurface injections and surface
      chemigations for 15 fumigant applications were combined with the physicochemical
      properties of the fumigants [vapor pressure, VP (Pa); water solubility, S(w) (mg
      L-1); soil adsorption coefficient, K(oc) (mL g-1)] and with application
      conditions [application rate, AR (kg ha-1); depth of application, d (cm)]. This
      resulted in the regression Ln ER = 3.598 + 0.9400 Ln R [R = (VP * AR)/(S(w) *
      K(oc) * d)], which can be used to estimate emissions for new applications.
      Emission rates derived from the linear correlation were used as input to an
      atmospheric dispersion model to estimate concentrations of fumigants in air at
      various downwind distances, and the results were compared with concentration
      values measured in the field near sources. The fumigant correlation along with an
      atmospheric dispersion model can be used as a rapid screening method by
      regulatory and enforcement agencies for exposure and risk assessment.

PMID- 21192107
TI  - Single layer of polymeric Fe-phthalocyanine: an organometallic sheet on metal and
      thin insulating film.
AB  - Supramolecular chemistry on a surface has produced a large variety of atomically
      controlled systems, but practical applications are seriously restricted by the
      use of weakly cohesive non-covalent bonds and by the confinement to a metal
      surface. Here we report on the formation of a well-ordered organometallic sheet
      consisting of two-dimensional polymeric phthalocyanine. Remarkably, the growth
      demonstrated on a metal surface can be extended onto a thin insulating film. We
      thus expect the intrinsic properties to be preserved, and the system should be
      easily transferable to real devices.

PMID- 21192108
TI  - Trigonosins A-F, daphnane diterpenoids from Trigonostemon thyrsoideum.
AB  - Phytochemical study of the roots of Trigonostemon thyrsoideum led to the
      isolation of four new oxygenated daphnane-type diterpenoids, trigonosins A-D (1
      4), and two new modified daphnanes, trigonosins E and F (5 and 6). The structures
      and relative configurations were elucidated on the basis of extensive
      spectroscopic analysis, including 1D and 2D NMR experiments. All compounds
      isolated were evaluated for their cytotoxicity against HL-60, A549, and MCF-7
      human cancer cell lines.

PMID- 21192109
TI  - Magnetic field-induced switching of the radical-pair intersystem crossing
      mechanism in a donor-bridge-acceptor molecule for artificial photosynthesis.
AB  - A covalent, fixed-distance donor-bridge-acceptor (D-B-A) molecule was synthesized
      that upon photoexcitation undergoes ultrafast charge separation to yield a
      radical ion pair (RP) in which the spin-spin exchange interaction (2J) between
      the two radicals is sufficiently large to result in preferential RP intersystem
      crossing to the highest-energy RP eigenstate (T(+1)) at the 350 mT magnetic field
      characteristic of X-band (9.5 GHz) EPR spectroscopy. This behavior is
      unprecedented in covalent D-B-A molecules, and is evidenced by the time-resolved
      EPR (TREPR) spectrum at X-band of (3*)D-B-A derived from RP recombination, which
      shows all six canonical EPR transitions polarized in emission (e,e,e,e,e,e). In
      contrast, when the RP is photogenerated in a 3400 mT magnetic field, the TREPR
      triplet spectrum at W-band (94 GHz) of (3*)D-B-A displays the (a,e,e,a,a,e)
      polarization pattern characteristic of a weakly coupled RP precursor, similar to
      that observed in photosynthetic reaction center proteins, and indicates a switch
      to selective population of the lower-energy T(0) eigenstate.

PMID- 21192110
TI  - Marginalisation of ethnic and religious minorities in Middle East history of
      medicine: the forgotten contributions to Arabian and Islamic medicine and
      science.
AB  - The contribution of ethnic and religious minorities to Arabian and Islamic
      medicine and science was a major and powerful one, yet it is rarely acknowledged.
      When remembered, it is often inaccurately referred to as "Arabic" or "Islamic",
      contrary to its ethnic and religious origins and identity. The objective of this
      study was to see whether such under-representation of ethnic and religious
      minorities is - singly or in combination - a random act, an act of ignorance,
      and/or an act of programmed marginalisation. We conducted a computerised PubMed
      search for all scholarly, peer-reviewed articles concerning medicine and science
      in the Middle East at the zenith of the Arabic and Islamic Empire from the 5th to
      the 12th century. The data was analysed using the binomial probability model. Our
      data indicates that the under-representation of ethnic and religious minorities
      and their contributions to Arabian and Islamic science and medicine is unlikely
      to be a random act. The findings suggest the possibility of ignorance and/or
      programmed marginalisation, attesting to the prevailing negative attitudes
      towards ethnic and religious minorities of the Middle East and their
      contributions to medicine and science.

PMID- 21192111
TI  - [Dr Ivan Christoph Nepomuk Daubach-Daubachy de Dolje Surgeon General of the
      Kingdom of Croatia in the MaZuranic-Brlic-RuZic memorial library and collection
      in Rijeka].
AB  - This study was preceded by one that brought together old and yet unpublished new
      information about the life and work of Ivan Daubachy (1766-1848), General Surgeon
      from Zagreb and his family that has left a distinguished mark in Croatian
      cultural history. German by origin, Dr Ivan Nepomuk Daubach (orig. Johann
      Christoph Nepomuk Daubach- Daubachy de Dolje), served in Zagreb as a military
      doctor on two occasions. There he soon got married, and settled for the rest of
      his life successfully pursuing private practice, public affairs, and the office
      of Croatian Surgeon General. For his merits, he received a hereditary title of
      nobility, and his daughters married into prominent families. The second part of
      this article describes the unknown legacy of Dr Daubachy and of his heirs that
      has been kept in the MaZuranic-Brlic-RuZic Memorial Library and Collection in
      Rijeka. It includes a number of objects and artefacts, but his manuscript with
      memoirs is of particular interest, and this is the first time these memoirs are
      being published bilingually in the original Latin and in Croatian translation.

PMID- 21192112
TI  - [Light and blindness in ancient Egypt].
AB  - In Ancient Egypt, light and fire, which were closely related to the Sun God Ra,
      were the sources of life and well-being, while the dark meant danger and death.
      Similar to death, darkness drops on human beings in deep sleep and they enter a
      space inhabited by shadows. Dreams were believed to reveal an unknown world, to
      give the sleeper a glimpse into the future. Vision attracts distant objects and
      their light, on the other hand, can hurt the eyes like a burning flame. Eyes were
      the most important organ in Egyptian thought, as they allowed perception of the
      real world. Their importance has been immortalised in the myth of the Eye of
      Horus that explains the role of either eye. One represents the moonlight, which
      disperses the darkness of the night, and the other represents the sunshine, which
      creates life, and both could also represents the power of human intellect.
      Blindness, in turn, congenital or disease-related, was considered a divine
      punishment. A man, thus handicapped, would sink in a state of uncertainty and
      darkness. To protect the eyes from blindness, people used drops and ointments,
      which were believed to chase away all kinds of insects and demons that threatened
      with a variety of eye infections. Egyptian eye doctors or physicians, carried a
      special kit that contained green chrysocolla and a black kohl makeup, highly
      appreciated as prophylaxis because they personified Osiris' humours or body
      fluids. These products were offered to Gods to restore the brightness of divine
      glance and incite sun and moon to spread their beneficial light.

PMID- 21192113
TI  - [Early Christian martyrs who refused to worship the cult of Asclepius in the
      times of Diocletian].
AB  - For centuries, theologists, historians, archaeologists, petrologists, and others
      had been interested in a story about Christian martyrs known as Passio Sanctorum
      Quattuor Coronatorum. It is a hagiographic manuscript from the 4th century which
      describes the martyrdom and death of two separate groups of Christians who
      suffered Diocletian's persecution. One group lived in Pannonia and the other in
      Rome. They refused to offer sacrifice to the ancient god of medicine Asclepius
      Roman Aesculapius. In the 6th century, their relics were kept in a basilica on
      the Coelian Hill in Rome, named after four saint martyrs Ss. Quattuor
      Coronatorum. In the Middle Ages, these saints enjoyed great glory, and many
      churches and chapels were dedicated to them in Italy, France, England, and
      Belgium. Guilds of stone workers and stone cutters took them for patrons. There
      are many copies of the Passio, which are kept in Vatican, Paris, Milan, Verona,
      Bern, and Munich. Beside the martyrdom story, these copies speak about
      inconsistencies related to the saints' names and place and time of the events
      described in the story. Our study brings together the most important findings
      made so far about this hagiographic mystery. Certain events described in the
      Passio are interpreted from the medico-historical aspect, which is a new approach
      to the subject.

PMID- 21192114
TI  - [Evidence of health culture in medieval statute of Budva].
AB  - The Statute of Budva dates from the time of Nemanjics. This medieval document was
      approved at the time Budva was under venetian dominion and remained in force
      until the end of the Venetian Republic. During 17th century the Statute was
      translated into the Italian language. The document includes regulations which
      indicate a concern for the health of the public. Among the regulations is one
      which prohibit the sale of fisch outside the stalls of the fishmarket presumably
      to ensure the sale of only fresh fish. Another regulation prohibits the sale of
      dead animals, the sale of dog's meat instead od wether meat. There is also
      language indicating a concern for protecting the cleanliness of brooks, rivers
      and wells. Corporal punishment is mentioned but only with regard to whipping and
      beheading.

PMID- 21192115
TI  - [Fra Dujo Ostojic (1863-1938) and his "Domaci Liecnik - medicus domesticus"].
AB  - Fra Dujo Ostojic(Bijakovici, 1863 - Humac kod Ljubuskog, 1938) was an educator,
      teacher, spiritual guide, pastor, cultural, political, charity and welfare
      activist, a bibliophile, collector, chronicler, and copyist, who worked all over
      Herzegovina. In 1913, he became Franciscan provincial in Mostar. He was also a
      member of the Bosnian and Herzegovinian parliament in Sarajevo, where he
      fervently advocated the rights, identity, and cultural and economic interests of
      the Croatian people of Herzegovina. At about the same time he bought printing
      machines from a local printer Dionicka tiskara and started a printing office that
      later became the well known Tiskara FP (FP - Franciscan Province). He continued
      to write his memoirs, adding new manuscripts to the volume. Two of them are worth
      of particular mention: "Domaci liecnik - Medicus domesticus" ("People's Doctor",
      1146 large format pages) and "Necrologium". There he describes the lives of
      Franciscan brothers and people he knew who practiced the art of pharmacy and
      medicine, and expands the recipes collected in healing books of the time. Unlike
      the manuscripts of some of his brothers, Ostojic's have survived for over seventy
      years to this day, to reveal his magnificent legacy to the Croatian people.

PMID- 21192116
TI  - [Health problems of the city of Split on the pages of the first newspaper written
      in Croatian language: "Il Regio Dalmata-Kraglski Dalmatin" (1806-1810): on the
      occasion of the 200th anniversary of termination of its publication].
AB  - At the beginning of the 19th century, one of the most important cultural events
      in Dalmatia was the publication of a bilingual newspaper Il Regio Dalmata -
      Kraglski Dalmatin in Italian and Croatian, issued by the French government in
      Zadar between 12 July 1806 and 22 January 1808. Between 29 January 1808 and 1
      April 1810 it changed name to Il Regio Dalmata. The journal paid much attention
      to the health problems of the city of Split, especially between 1806 and 1808.
      The aim of this study was to analyze the original articles published in this
      first newspaper in Croatian language and to understand the role of this
      publication as means of promoting health policies in Split. The journal published
      articles about health care for the poor and foundlings, about the need for
      charity institutions to refer them to the city hospital and to the foundling
      home, and encouraged citizens to help maintain these institutions. Great
      attention was also dedicated to vaccination against smallpox and demographic
      problems of Split. Thanks to Croatian, Il Regio Dalmata-Kraglski Dalmatin
      informed a wider audience about the existing health conditions in the city of
      Split and about the efforts of the French government for its improvement.

PMID- 21192117
TI  - Language and medicine in the Zamenhof family.
AB  - The Zamenhof family is famous for Dr Ludwik Lejzer Zamenhof (1859-1917), who
      created the artificial language Esperanto and who initiated a social movement for
      peace and against any sort of discrimination. Ludwik was an ophthalmologist.
      Adam, Leon, Alexander, and Julian Zamenhof were medical doctors and noted
      surgeons, while Sophia Zamenhof was a paediatrician. Ludwik Zamenhof often
      referred to the biblical story of the Tower of Babel, in which diversity of
      languages was the punishment for builders who were arrogant and uncaring. With
      the help of Esperanto, the Zamenhofs metaphorically wanted to overcome the curse
      of Babel and restore the sense of human unity.

PMID- 21192118
TI  - [The physician between the ideal and reality: medical profession and popular
      attitude towards health and medicine in the 19th century].
AB  - This paper studies the attitude of the society towards the medical profession,
      which was torn between high social expectations and ideals and medical practice
      confronted with real-life obstacles. In the 19th century, the physician's
      position was still precarious and called for a renegotiation in the community.
      Physician's work was faced with people's distrust and resistance, superstitions
      and prejudices, folk medicine and religion. Even such ideal qualities as dignity,
      conscientiousness, and courage, would quickly be called into question by events
      such as epidemics. Particularly in 19th century rural areas, the physician's
      position was far from acknowledged and official medicine had yet to win people's
      trust. This paper explores the polyvalent attitude of people towards medicine and
      health. It investigates the discourse used to describe health and medicine in
      daily press, professional and popular literature, as well as in official medical
      documents of the time. It shows a long struggle of public health care to gain
      people's approval. During cholera epidemics, which apart from presenting serious
      threat to human life were an opportunity for medicine to win people's trust and
      obedience, the attitude towards health gradually began to change. To some extent
      this was a result of medical advances, new scientific discoveries, and increasing
      success in abating the epidemics. At the same time, as the society became more
      secular, medicine slowly gained people's trust and gradually replaced the healing
      methods of folk medicine. Health was less and less understood as a result of
      God's will and mercy, and the attitude towards disease began to evolve from
      passive resignation to an active battle for health.

PMID- 21192119
TI  - Sanitary conditions in the city of Fiume (Rijeka) at the of the 19th century.
AB  - The Municipal Sanitary Commission (Commisione sanitaria municipale) was founded
      in Fiume (Rijeka) at the end of the 19th century. The well known physician of the
      municipal hospital, Dr. Antonio Grossich was its first president. In his
      inaugural speech he pointed out the mortality within the city during the last
      decade as 28 0/00. Based on the monthly reports from the municipal physicians,
      Dr. Giovanni Benzan evaluated the mortality within the city as 25,9 0/00 in 1900.
      Mortality of children under age of five accounted for almost half of the
      estimated mortality (11,40/00), while contribution of tuberculosis was the second
      (5,80/00). Feeding with cow milk caused considerable mortality among small
      children, thus pointing to the necessity for milk control in the market. He also
      proposed destruction and resettling the population from the inner city area with
      poor sanitary conditions. In his opinion, municipal authorities' duty was to
      educate the population to promote hygiene, e.g. disinfection of homes and cloth,
      in order to prevent tuberculosis. Dr. Benzan complained about hygiene in the old
      inadequate school buildings, with technical faults. He proposed the systematic
      check-up of school children. He pointed out the importance of the new water
      supply system, that led to eradication of typhus in the city. The problem of
      dusty roads though remained, and his solution was to wash the streets. He
      promoted food control, hygiene in public places and disinfection of sewage water.
      His plans included building up of the new municipal hospital, waste incinerator,
      crematorium, public and sea-side bath, new hostel for workers immigrating into
      the city.

PMID- 21192120
TI  - Development of ophthalmology in Slovenia and University Eye Hospital in Ljubljana
      (1890-2010): at the 120th anniversary of the University Eye Hospital in
      Ljubljana.
AB  - Slovenian ophthalmology developed much at the same time as in the rest of the
      Central Europe). The first Slovenian ophthalmologist was Dr Ludvik Grbec
      (1805%emdash;1880). The first Slovenian eye department was established within the
      Ljubljana civil hospital in 1890, and initially counted 34 hospital beds. Under
      Dr Emil Bock, the department grew to 120 beds by 1916 and saw a number of
      surgical procedures performed (mainly cataract operations). Dr Bock also founded
      a department for the treatment of ocular tuberculosis in children. From 1920 to
      1958, the department was resumed by Dr Leopold Jese, a pioneer of Slovenian
      ophthalmology, the first professor of ophthalmology at the Ljubljana University
      Faculty of Medicine (1945), author of the first ophthalmology textbook for
      students (Ophthalmology, 1946), and the father of Slovenian ophthalmological
      terminology. This article describes the development of ophthalmology in Slovenian
      hospitals to this day, especially in the Ljubljana Eye Hospital. It remembers the
      most prominent figures and professional, educational,and scientific achievements.
      Now in 2010, Slovenia has over 130 ophthalmologists, two departments teaching
      ophthalmology (within Ljubljana and Maribor University Faculties of Medicine), an
      internationally recognised ophthalmology specialisation programme, and
      influential research work published in various journals indexed by Science
      Citation Index.

PMID- 21192121
TI  - [Remembrance of the Metkovic War Hospital (1991-1996): on occasion of the
      twentieth anniversary of its foundation].
AB  - The valley of the Neretva river, inhabited with about forty thousand people, is
      over one hundred kilometres away from the nearest hospital, which becomes
      particularly problematic in cases of mass casualties. During the Liberation War
      from January 1991 to June 1996, the War Hospital Metkovic was organized in the
      Neretva valley region. This paper deals with the activities of this hospital. The
      documentary basis for this paper consists of surgery protocols, records of day
      clinic checkups at the War Hospital Metkovic, articles from the press of the
      period, private correspondence and secondary sources. In the analysed period,
      1.831 people wounded in war were successfully treated in this hospital, and there
      were also 12.000 one-time checkups. The work and activities of war hospitals
      represent important chapters in the history of medicine. Research of the
      organization and functioning of these institutions contributes to the development
      of insights and experiences regarding organized medical care in the zone of
      immediate war activities.

PMID- 21192122
TI  - Anaesthesiology activities in Croatia from the first ether narcosis in Zadar in
      1847 to 2008.
AB  - This is a short review of the historical development of anaesthesiology and
      intensive care in Croatia from its beginning to recent days (2008). Five months
      after the first public demonstration of ether anaesthesia in the USA, Ivan
      Bettini followed with the first ether anaesthesia in Zadar, on 13 March 1847. In
      the 19th century and the first half of the 20th century, the following doctors
      wrote about performing anaesthesia: Miroslav Cackovic (in 1896), Dragutin
      Schwarz, Edo Slajmer, Milan Crljenak, Antun Medanic, BoZidar Lavric, Simo
      Mucalov, Josip Vodenhal, Ante Drescik, Radoslav Akerman, and Durda Klaic. The
      first endotracheal anaesthesia, was induced by Dr Risto Ivanovski at the military
      hospital in Zagreb in 1948. Croatian anaesthesiology started to develop in 1950
      with the introduction of a one-year postgraduate course in Copenhagen, within the
      framework of a WHO programme, intended for underdeveloped and developing
      countries and overseen by the WHO Centre for Anaesthesiology. Croatian physicians
      attending this course were Andrija Longhino, Jagoda Bolcic Wickerhauser, Miroslav
      Hromadko, Mara Biondic, and Vlasta Lederer. The first specialists in
      anaesthesiology in Croatia were urda Klaic, Ljubomir Ribaric, and Jagoda Bolcic
      Wickerhauser. In Zagreb, the first postgraduate courses in anaesthesiology were
      held in 1953, 1955, and 1957. In 2007, the anaesthesiology service in Croatia
      consisted of three Anaesthesiology and Intensive Care Clinics, three
      Anaesthesiology and Intensive Care Departments, 11 Anaesthesiology and Intensive
      Care Units, 13 Anaesthesiology and Resuscitation Services, and eight
      Anaesthesiology Units within Surgery Departments. It included 481 specialists in
      anaesthesiology and resuscitation and 172 general physicians specialising in
      anaesthesiology and resuscitation (totalling 653 in December 2007). This means
      that one specialist serviced 9,140 people, that is, 6,730 if we include GPs
      undergoing specialist training. Anaesthesiologists in charge of intensive care
      units covered 364 beds.

PMID- 21192123
TI  - [Dr Mavro Sachs (1817-1888): the first lecturer of Zagreb University].
AB  - Mavro Sachs (Janoshaza, Hungary, 1817 % emdash; Rijeka, 1888.) was a Zagreb
      student since 1828. In 1846 he graduated in medicine from the University of
      Vienna and returned to Zagreb to be the city physician. In 1849, he started to
      teach forensic medicine at the School of Law of the Royal Academy of Sciences in
      Zagreb and continued teaching the same subject at the Zagreb University Faculty
      of Law in the capacity of docent (corresponds to lecturer in the British system).
      He also taught medical law at pharmaceutical studies of Zagreb University. From
      1855 to 1860, he presided over the Jewish Community of Zagreb.

PMID- 21192124
TI  - Hormonal crosstalk with calcium channel blocker during implantation.
AB  - The site specific action of the calcium channel blocker diltiazem in blocking
      prostaglandin synthesis and hence causing blastocyst implantation failure has
      been previously described. Based on this understanding it was important to learn
      if this pathway was under the control of the fine balance in estradiol
      progesterone (E2-P4) milieu, considered to be of the utmost significance for
      effective implantation. In the current study the circulating E2-P4 levels were
      monitored on the first 6 d of pregnancy at various time points using sensitive
      chemiluminescence based assays. Next, diltiazem was administered intra-luminally
      into the uterus at 10-20 h prior to implantation as this time has been previously
      implicated to be when the best anti-implantation activity of diltiazem can be
      observed. Following this, the E2-P4 in peripheral circulation was again
      monitored. On d 6 (post implantation) the implantation sites were observed in the
      uterus of both diltiazem treated and untreated groups using Chicago blue dye and
      correlated to the hormonal activity. The levels of both estradiol and
      progesterone were very similar in both untreated and diltiazem treated groups
      during and post implantation. However complete implantation failure was noted in
      the diltiazem treated group whereas prominent implantation sites were observed in
      the untreated animals. Thus, the previously reported inhibition of blastocyst
      implantation cascade by calcium channel blockers during the 'implantation window'
      seems to be an independent mechanism interfering with uterine receptivity without
      any direct estrogen-progesterone control and further studies to understand its
      regulation need to be performed.

PMID- 21192127
TI  - [The challlenge of improving the quality of the Revista de la facultad de
      Ciencias Medicas].

PMID- 21192125
TI  - The association between naltrexone treatment and symptoms of depression in opioid
      dependent patients.
AB  - OBJECTIVE: To examine the change in total symptoms, and symptom clusters, of
      depression in newly abstinent opioid-dependent individuals being treated with
      depot naltrexone (Depotrex; Biotek, Inc., Wellesley, MA). METHOD: In a series of
      opioid-dependent patients (N = 34) treated with naltrexone maintenance and
      relapse prevention therapy, mood was assessed with a 17-item Hamilton Depression
      (HAM-D) Scale and subscale scores at baseline, and after naltrexone induction at
      2- and 4-week post-baseline. Data were analyzed using generalized estimated
      equation (GEE) models. RESULTS: Patients demonstrated high baseline affective
      burden and significant improvement of depression scores over a 4-week period post
      baseline (F(2.66) = 8.88; p = .0004). Somatic and cognitive-affective subscale
      scores significantly declined as well as the seven individual item scores. By
      contrast, the "late insomnia" item score significantly increased at 2 weeks post
      baseline. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Naltrexone induction and
      maintenance in newly abstinent opioid-dependent individuals does not appear to be
      associated with worsening of depression; however, it may be associated with sleep
      impairment early in treatment.

PMID- 21192128
TI  - [Efficacy and securyty of therapeutic hypothermia for hypoxic ischemic
      encephalopathy: a meta-analysis].
AB  - BACKGROUND: Animal and human experimental models suggest that therapeutic
      hypothermia could reduce neurological disabilities in asphyxiated newborn without
      adverse events. The objective of this study was review the effectiveness and
      safety of hypothermia as treatment for hypoxic ischemic encephalophaty. METHODS:
      MEDLINE, COCHRANE LIBRARY, Academic Google and LILACS databases were searched.
      Randomized controlled trials with main outcomes of death, neurodevelopmental
      disability and adverse events were eligible for inclusion in the meta-analysis.
      RESULTS: Tree studies were included with 751 patients. Combined results of death
      reduction was not significant (RR 0.83 CI95% 0.67 to 1.04). Severe to moderate
      neurodevelopmental disability (RR 0.70 CI95% 0.55 to 0.89) and cerebral palsy (RR
      0.66 CI95% 0.50 to 0.89) were reduced significantly in newborns receiving
      hypothermia compared with controls. Cardiac arrhythmias (RR 3.51 CI95% 1.29 to
      9.54) and coagulation disorders (RR 1,23 CI95% 1.03 a 1.48) were more common
      adverse events with hypothermia. CONCLUSIONS: Hypothermia is effective in
      reducing neurological disability and cerebral palsy. Cardiac arrhythmias and
      coagulation disorders were more common with hypothermia, however they were
      clinically benign.

PMID- 21192129
TI  - [Design of a simple score to predict the etiology of pneumonia in children].
AB  - BACKGROUND: The etiology of pneumonia is important to indicate antibiotics. A
      clinical prediction score (RP) has been designed, although the radiological
      interpretation is not easy. OBJECTIVE: To design a simple prediction score (PRs)
      to identify etiology in children with pneumonia, including radiological patterns,
      clinical and laboratory features. METHODS: Cross sectional study. We
      prospectively included children under 5 years hospitalized for pneumonia with
      microbiological evidence (2007-2008). According to the RP, were allocated 3
      points when the temperature value was >= 39 o C, 2 when the patient age was >= 9
      months, 2 when the number of neutrophils was 8000/mm3 and 1 when the immature
      neutrophils number was >= 5%. Radiography was evaluated as one point when
      consolidation was diagnosed and 0 point when pleural effusion or other
      infiltrations were present. RPS range was from 0 to 9 points. We determined the
      best cutoff for predicting bacterial pneumonia (ROC) and was calculated based on
      the same sensitivity (S), specificity (Sp), positive predictive value (PPV) and
      negative (NPV) and positive likelihood ratio ( RVP) and negative (NLR). RESULTS:
      196 patients (viral: 82%, bacteria: 18%), 8.7 +/- 10 months. We identified a
      score >= 3 (auROCc = 0.87 95% CI 0.81 to 0.94) as the best point to predict
      bacterial pneumonia (S: 88.6%, E: 68.9%, PPV: 38.3 %, NPV: 96.5% RVP: 2.85; RPN:
      0.17). CONCLUSION: The PRs showed an acceptable performance, but less sensitive
      than the original score to predict bacterial pneumonia. Although this tool may be
      easily applied, it should be validated in future studies.

PMID- 21192130
TI  - [Effect of UV index in the skin exposure].
AB  - This research was conducted from October 2003 to March 2005, collecting data
      through the measuring authorized volunteers measuring their photoexposition . It
      worked with the equipment (Safesun from Optix Tech, Inc.), available for
      measuring. The radiation impact of solar on the city of Cordoba, was chosen
      measurements for a clear spot on the terrace of the Observatory Environmental
      Laprida located at 854, in a position that excedes level approximately 30 meters
      from Piazza San Martin (centerhistoric city). It had two fixed radiation sensors
      total solar and ultraviolet A radiation sensor manual ultraviolet calibrated
      according to the erythemal response of skin measuring human ultraviolet index and
      the maximum exposure timer ecommended for different skin types (Safesun from
      Optix Tech, Inc.).The aim of this study was to measure the rate and exposure
      ultraviolet (UV) to evaluate the erythemal effect on most sensitive areas of the
      face and neck to noon fotoexposicion solar in the four annual seasons, and thus
      promote extending protection regulations to prevent the effects harmful UV non
      ionizing radiation. The analysis of the data, UV index values indicate that from
      the Winter season is observed to undergo the risk of exposure excessive radiation
      at noon solar day is measured with high Fall UV index is high in spring and high
      very high and with days end in the Summer season daily with UV index very high
      and extreme. This risk remains in the four annual seasons and according to the
      criteria of the World Health Organization is need to perform significant work to
      develop measures, education campaigns and outreach, which tend to diminish the
      sun exposure, hours with the highest incidence of lightning ultraviolet in the
      four annual seasons. The global environmental degradation and thus destruction of
      the ozone layer, has been a direct cause of the increase in ultraviolet radiation
      on earth, which resulted increased rates of cancer incidence and prevalence skin,
      within the population.

PMID- 21192131
TI  - [Clinical manifestations of antiphospholipid syndrome].

PMID- 21192132
TI  - A study of success predictors in the entrance examination to the school medicine
      (2006-2008).
AB  - Institutions involved in training health professionals are permanently concerned
      with improving the quality of their graduates and their skills for meeting
      healthcare demands. Research has been conducted in the field of health education
      and related areas with the purpose of identifying the incidence of high-school
      GPAs, learning styles and demographic factors on pre-university performance of
      students. It has been widely assumed that performance at this stage is one of the
      best predictors of subsequent academic performance. In the year 2000 the School
      of Medicine of the Universidad Nacional de Cordoba introduced an Entrance
      Examination as part of a comprehensive curricular reform. Therefore, the study of
      the predictors of performance in the entrance examination can be a valuable
      contribution to pedagogical decision making. Our aim is to assess the predictive
      capacity of a series of indicators associated to the population of candidates
      attempting entrance to medical studies. The survey comprises the period 2006
      2008. The variables under study are: sociodemographic characteristics, high
      school specialization, and high-school grade point average (GPA). ANOVA was
      applied to measurable variables, whereas attribute variables were submitted to
      categorical data and multiple correspondence analyses. We conclude that
      predictors are associated to sociocultural factors related to family environment,
      mainly educational level of the mother, and to a high-school GPA value between 8
      and 9 points.

PMID- 21192133
TI  - [Posterior locked shoulder fracture-dislocation: anatomical resconstruction of
      reverser Hill-Sachs lession].
AB  - The posterior instability of the shoulder only represents 4% of the shoulder
      instabilities. For the diagnosis, the antero-posterior, transtoracic and axilar
      radiographic projections are recommended. The inverted Hill-Sachs lesion is a
      fracture caused by compression of the antero-medial part of the humeral head
      during the posterior dislocation. Its treatment results, at least, controverted.
      Choosing the treatment of these lesions one of the main factors is the size of
      the defect in the humeral head. When it is smaller than 20%, the simple reduction
      usually is enough. Between 20-40%, we can opt for a transposition of the
      subescapular insertion to the bony defect (technique of MacLaughlin) or the
      anatomical reconstruction of the head by means of the fixation of an allograft.
      The transposition of the subescapular's tendon carries a reduction of the
      internal rotation by medializing its insertion, for this reason, we opted for the
      anatomical reconstruction with allograft of femoral head that reestablishes the
      muscular balance. The shoulder artroplasty is elective when bony defects are
      bigger (>40-50 % of the articulation surface). We present the case of a 32 year
      old patient, with the antecedent of convulsive crisis. Clinically he suffered
      intense pain with functional impotence and elastic limitation for the external
      rotation in left shoulder. The radiographic studies evidenced an instable
      posterior fracture-dislocation with inverted Hill-Sachs lesion associated that
      involved the 30% of the articular surface. The patient was surgically treated,
      opting for a reconstructive technique for humeral head. After six months, the
      range of motion is almost symmetrical with regard to the healthy shoulder,
      without any clinic of instability.

PMID- 21192134
TI  - Psychotropic drug prescribing in the United States: extent, costs, and
      expenditures.

PMID- 21192135
TI  - High correlation between serum and cerebrospinal fluid olanzapine concentrations
      in patients with schizophrenia or schizoaffective disorder medicating with oral
      olanzapine as the only antipsychotic drug.
AB  - The primary aim of the present study was to investigate the relationship between
      steady state serum and cerebrospinal fluid (CSF) concentrations of olanzapine
      (OLA) and its metabolite 4'-N-desmethylolanzapine (DMO) in patients with
      schizophrenia or schizoaffective disorder treated with oral OLA as the only
      antipsychotic drug. The influence of smoking, gender, age, as well as
      polymorphisms in cytochrome P450 CYP2D6, CYP1A2, and ABCB1 genes on the serum and
      CSF drug levels was also analyzed. Thirty-seven white outpatients (10 smokers and
      27 nonsmokers) were included. From 29 of them, CSF was collected successfully. A
      strong correlation (Spearman rank correlation [rs] = 0.93; P < 0.05) was found
      between serum and CSF concentrations of OLA and a somewhat weaker correlation (rs
      = 0.5; P < 0.05) between those of DMO. The CSF concentrations of OLA and DMO were
      on average 12% and 16% of those in serum. Extensive metabolizers of CYP2D6 had
      higher (P < 0.05) daily doses than poor metabolizers when the influence of
      smoking was taken into account. Smokers had lower (P < 0.01) concentration-to
      dose ratios of OLA in serum (mean, 2.23 ng/mL per mg vs 3.32 ng/mL per mg) and
      CSF (0.27 ng/mL per mg vs 0.41 ng/mL per mg) than nonsmokers. The concentration
      to-dose ratio for serum DMO decreased with increasing age (rs = -0.41; P < 0.05).
      Carriers of ABCB1 1236T/2677T/3435T haplotype had higher serum (mean, 37.7 ng/mL
      vs 22.5 ng/mL; P = 0.035) and CSF (4.7 ng/mL vs 2.6 ng/mL; P = 0.018) OLA
      concentrations than patients without this haplotype. The present study shows a
      strong correlation between serum and CSF concentrations of OLA, indicating that
      concentrations of OLA in serum reflect those in CSF.

PMID- 21192136
TI  - Predictors of the discharge dosage of an atypical antipsychotic agent among
      hospitalized, treatment-naive, first-episode psychosis patients in naturalistic,
      public-sector settings.
AB  - OBJECTIVE: Little is known about determinants of second-generation antipsychotic
      dosages during initial hospitalization of first-episode psychosis. This study
      examined potential predictors of dosage of an atypical antipsychotic agent,
      risperidone, at hospital discharge after initial evaluation and treatment of
      first-episode nonaffective psychosis in 3 naturalistic, public-sector treatment
      settings. METHODS: The number of psychotropic agents prescribed and discharge
      antipsychotic dosage were abstracted from the medical record. Demographic and
      extensive clinical characteristics were assessed through a clinical research
      study conducted at the 3 sites. One-way analyses of variance, trend tests using
      specific linear combinations of estimates, and chi2 tests assessed for
      associations between atypical antipsychotic dosage and 5 hypothesized predictors,
      as well as 12 exploratory variables. RESULTS: Among 155 hospitalized first
      episode patients, 121 (78.1%) were discharged on risperidone, and subsequent
      analyses focused on that subset. The mean risperidone dosage among those 121
      patients was 4.26 mg; 31 received 1 to 2 mg, 45 received 3 to 4 mg, 37 received 5
      to 6 mg, and 8 received more than 6 mg. Analyses suggested that older age at
      hospitalization, the number of psychotropic agents prescribed, excited symptoms,
      and premorbid social functioning may be predictors of the discharge dosage.
      CONCLUSIONS: Although several factors emerged, in general, predictors of
      discharge dosages of second-generation agents, here exemplified by risperidone,
      in real-world practice settings remain to be clarified. Given the importance of
      antipsychotic initiation during first hospitalization, future research should
      test an even broader array of potential predictors.

PMID- 21192140
TI  - The relationship between adverse events during selective serotonin reuptake
      inhibitor treatment for major depressive disorder and nonremission in the suicide
      assessment methodology study.
AB  - Little is known about the association between antidepressant treatment-emergent
      adverse events and symptom nonremission in major depressive disorder. The
      objective of the current analysis was to determine whether particular baseline
      symptoms or treatment-emergent symptoms (adverse events) during the first 2 weeks
      are associated with nonremission after 8 weeks of treatment with a selective
      serotonin reuptake inhibitor (SSRI).Outpatients clinically diagnosed with
      nonpsychotic major depressive disorder were recruited from 6 primary and 9
      psychiatric care sites. Participants (n = 206) were treated with an SSRI
      antidepressant (citalopram [20-40 mg/d], escitalopram [10-20 mg/d], fluoxetine
      [20-40 mg/d], paroxetine [20-40 mg/d], paroxetine CR [25-37.5 mg/d], or
      sertraline [50-150 mg/d]) for 8 weeks. Remission was defined as having a score of
      5 or less on the 16-item Quick Inventory of Depressive Symptomatology-Clinician
      Rated at week 8, or using last observation carried forward. Adverse events were
      identified using the 55-item Systematic Assessment for Treatment Emergent Events
      Systematic Inquiry completed by participants at baseline and week 2.Findings
      indicated that the emergence of adverse events of weakness/fatigue, strange
      feeling, and trouble catching breath/hyperventilation at week 2 were
      independently associated with lack of remission even after controlling for the
      potential confounders of baseline depressive severity, anxious symptoms,
      antidepressant medication, chronic depression, race, burden of general medical
      comorbidity, and time in study. Hearing/seeing things appeared to have a
      protective effect. In conclusion, during SSRI treatment, the adverse events of
      weakness/fatigue, feeling strange, and trouble catching breath/hyperventilation
      are associated with nonremission, possibly due to lower adherence, early
      attrition, difficulty increasing the dose, and reduced efficacy.

PMID- 21192139
TI  - A double-blind, randomized trial of sertraline for alcohol dependence: moderation
      by age of onset [corrected] and 5-hydroxytryptamine transporter-linked promoter
      region genotype.
AB  - Late-onset/low-vulnerability alcoholics (LOAs) appear to drink less when treated
      with a selective serotonin reuptake inhibitor than placebo, whereas early
      onset/high-vulnerability alcoholics (EOAs) show the opposite effect. We conducted
      a 12-week, parallel-group, placebo-controlled trial of the efficacy of sertraline
      in alcohol dependence (AD). We compared the effects in LOAs versus EOAs and
      examined the moderating effects of a functional polymorphism in the serotonin
      transporter gene. Patients (N = 134, 80.6% male, 34.3% EOAs) with Diagnostic and
      Statistical Manual of Mental Disorders-IV AD received up to 200 mg of sertraline
      (n = 63) or placebo (n = 71) daily. We used urn randomization, and patients were
      genotyped for the tri-allelic 5-hydroxytryptamine transporter protein linked
      promoter region polymorphism. Planned analyses included main and interaction
      effects of medication group, age of onset (<= 25 years vs >25 years), and
      genotype (L'/L' vs S' carriers) on drinking outcomes. Results showed that the
      moderating effect of age of onset on the response to sertraline was conditional
      on genotype. There were no main or interaction effects among S' allele carriers.
      However, in L' homozygotes, the effects of medication group varied by age of
      onset (P = 0.002). At the end of treatment, LOAs reported fewer drinking and
      heavy drinking days when treated with sertraline (P = 0.011), whereas EOAs had
      fewer drinking and heavy drinking days when treated with placebo (P < 0.001). The
      small cell sizes and high rate of attrition, particularly for L' homozygotes,
      render these findings preliminary and their replication in larger samples
      necessary. Because AD is common, particularly in medical settings, and selective
      serotonin reuptake inhibitors are widely prescribed by practitioners, these
      findings have potential public health significance and warrant further
      evaluation.

PMID- 21192138
TI  - Clinical and demographic characteristics associated with postural instability in
      patients with schizophrenia.
AB  - As people with schizophrenia grow older, prevention of falls in this older
      population has become a public health priority. It is therefore critically
      important to identify risk factors to effectively prevent falls. For this
      purpose, the degree of postural sway can serve as a convenient index of risk
      assessment. The objective of this study was to find clinical and demographic
      characteristics associated with postural instability. Inpatients and outpatients
      with schizophrenia or related psychosis were recruited at 2 hospitals in Japan.
      The clinical stabilometric platform, which measured a range of the trunk motion,
      and extrapyramidal side effects were evaluated between 9 and 11 A.M. Four hundred
      two subjects were enrolled (age: mean, 55.5 [SD, 14.4] years). A univariate
      general linear model showed that the use of antipsychotic drugs with a
      chlorpromazine equivalent of 10 or greater, being overweight, and inpatient
      treatment setting were associated with a greater degree of the range of postural
      sway. Another general linear model, including a subgroup of 300 subjects who did
      not present any extrapyramidal side effects, not only consolidated these
      findings, but also revealed a great degree of postural sway in older subjects. In
      addition, quetiapine was found to be associated with a greater range of postural
      sway among atypical antipsychotics. Schizophrenia patients generally showed a
      greater degree of postural instability, compared with the reference data of
      healthy people. These findings highlight truncal instability as a risk factor of
      falls in patients with schizophrenia, especially when they are overweight, old,
      and/or receiving antipsychotics with a chlorpromazine equivalent of 10 or
      greater, including quetiapine.

PMID- 21192141
TI  - Major depressive disorder: gender differences in symptoms, life quality, and
      sexual function.
AB  - OBJECTIVE: To investigate the gender differences of symptoms, life quality,
      functional impairment, and sexual function of patients with moderately severe
      major depressive disorder (MDD). METHOD: One hundred forty-six outpatients with
      MDD were enrolled into this study with specific selection criteria (male, 57;
      female, 89; mean +/- SD age, 38.30 +/- 11.69 years). All the patients self-rated
      the Quick Inventory of Depressive Symptomatology--Self-Report (QIDS-SR16) and the
      Integral Inventory for Depression (IID) for the assessment of symptoms assessment
      as well as the EuroQol life quality scale (EQ5D) was for the subjective life
      quality, the Sheehan disability scale was for the functional impairments, and the
      Arizona Sexual Experience Scale was for sexual function evaluation. All data were
      analyzed to estimate correlation and gender difference. RESULTS: Female patients
      had higher scores of the QIDS-SR16, IID, and Arizona Sexual Experience scales.
      Significant gender differences of sadness, sleep, appetite, calmness, painful
      symptoms, and sexual functioning were observed. The female-specific sexual
      dysfunctions included lower sexual drive, lower sexual arousal, lower horny
      feelings, lower orgasms, and lower satisfaction of orgasm. The MDD episodes were
      related to the EuroQol life quality scale and the SDS. Interepisode years were
      associated with the IID. The Sheehan disability scale was correlated with QIDS
      SR16 with statistical significance. CONCLUSIONS: Patients with MDD showed a
      correlation between symptoms and functional impairment. Female patients might be
      more sexually impaired, more vegetative, more depressed, and experiencing more
      sadness and physical pain.

PMID- 21192142
TI  - beta-blockers and the risk of incident depression in the elderly.
AB  - The hypothesis that beta-blockers cause depression has been both confirmed and
      refuted in previous studies. However, in hardly any of these studies, depression
      was systematically and adequately assessed. The aim of this cohort study was to
      examine whether beta-blockers, in general, highly lipid-soluble, nonselective, or
      serotonergic receptor-binding beta-blockers, are associated with incident
      depression. Between 1993 and 2005, 5104 elderly persons were followed for
      incident depressions. Depressions were identified by regular interview and
      continuous monitoring of medical records. Cases were categorized as clinically
      relevant depressive symptoms or as depressive syndromes, the latter including
      Diagnostic and Statistical Manual of Mental Disorders-IV-defined depressive
      disorders. Pharmacies provided information on filled beta-blockers. We used Cox
      regression with drug use as a time-dependent variable to analyze the data,
      adjusted for potential demographic covariates, activity of daily living, and
      (contra)indications for beta-blockers. We found that use of beta-blockers in
      general did not convey an increased risk of depressive symptoms (hazard ratio
      [HR], 0.76; 95% confidence interval [CI], 0.37-1.59) or depressive syndromes (HR,
      0.99; 95% CI, 0.53-1.84). Highly lipid-soluble beta-blockers, mostly propranolol
      in our study, were associated with depressive symptoms during the first 3 months
      of use (HR, 3.31; 95% CI, 1.03-10.6), but not with depressive syndromes.
      Nonselective or serotonergic receptor affinity was not associated with an
      increased risk of depressive symptoms or syndromes independent of high lipid
      solubility. We conclude that beta-blockers in general do not convey an increased
      risk of depression. Lipophilic beta-blockers are associated with an increased
      risk of depressive symptoms.

PMID- 21192143
TI  - Effect of methylphenidate on intelligence quotient scores in Chinese children
      with attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: Stimulants are the most effective drugs for attention
      deficit/hyperactivity disorder (ADHD) symptoms. The purpose of this study was to
      explore the intervention effect of methylphenidate, a commonly used stimulant, on
      cognitive performance in ADHD children and whether the effect is associated with
      age, sex, different subtypes of ADHD, and drug dosage. METHODS: Children with
      ADHD were divided into the following subtypes: combined type, predominantly
      inattentive type, and hyperactive/impulsive type. The intervention group
      consisted of 159 children treated with methylphenidate, and the control group
      consisted of 78 untreated patients. All 237 subjects were given a Wechsler
      Intelligence Scale for Children--Revised test at baseline, and 6 months later,
      they were retested. The scores of Verbal Intelligence Quotient (IQ) test,
      Performance IQ (PIQ) test, Full Scale IQ (FSIQ) test, and subtests were compared
      before and after the intervention. RESULTS: At baseline, scores were not
      statistically different between the 2 groups. After 6 months, PIQ and FSIQ scores
      of intervention group were higher than those of the control group (P < 0.05).
      Compared with baseline scores, the intervention group, but not the control group,
      showed significant increases in Verbal IQ (P < 0.05), PIQ (P < 0.01), and FSIQ (P
      < 0.01). In the intervention group, the 5 subtests scores of PIQ improved
      significantly (P < 0.01). In the control group, none of the scores from the
      subtests showed statistical differences. Furthermore, there was no statistical
      difference between the change of IQ scores and children's age, sex, different
      subtypes of ADHD, and drug dosage. CONCLUSIONS: Methylphenidate can enhance
      cognitive performance in ADHD patients thus evaluating their IQ scores, although
      the effect size seems to be relatively small. The result should not be indicated
      as an increase in intelligence.

PMID- 21192144
TI  - Risk of low bone mineral density associated with psychotropic medications and
      mental disorders in postmenopausal women.
AB  - BACKGROUND: Independent reports suggest that various psychotropic medications and
      psychiatric disorders are associated with changes in bone mineral density (BMD).
      The objective of this study was to clarify the independent effects of a range of
      mental illnesses and psychotropic medications on BMD among postmenopausal women.
      METHODS: Women 50 years or older with baseline BMD measured by dual-energy x-ray
      absorptiometry were identified in a database containing all clinical dual-energy
      x-ray absorptiometry test results for the Province of Manitoba, Canada. Records
      were linked with population-based administrative health databases to provide
      detailed information on sociodemographic factors, mental and physical health
      diagnoses, and prescription medication usage. Osteoporotic cases (n = 6820) were
      matched on age, sex, and ethnicity to 3 control subjects with normal BMD (n =
      20,247). Multivariable conditional logistic regression compared cases and control
      subjects on diagnosed mental illnesses and use of psychotropic medications.
      RESULTS: Selective serotonin reuptake inhibitors (adjusted odds ratios, 1.46; 95%
      confidence interval [CI], 1.25-1.69), atypical antipsychotics (AOR, 1.55; 95% CI,
      1.06-2.28), and benzodiazepines (AOR, 1.17; 95% CI, 1.06-1.29) were associated
      with higher risk of osteoporosis. Tricyclic antidepressants were associated with
      lower odds of osteoporosis (AOR, 0.57; 95% CI, 0.49-0.65). These drug effects
      were independent of mental illness diagnoses including depression (AOR, 0.86; 95%
      CI, 0.75-0.98) and schizophrenia (AOR, 1.98; 95% CI, 1.04-3.77). CONCLUSIONS:
      Some psychotropic medications are associated with an increased risk of
      osteoporotic BMD, whereas tricyclic antidepressants may be protective against
      osteoporosis, and these effects are independent of mental illness diagnoses.
      Clinicians should consider these effects when prescribing psychotropic
      medications in postmenopausal women.

PMID- 21192145
TI  - Lamotrigine in the immediate treatment of outpatients with depersonalization
      disorder without psychiatric comorbidity: randomized, double-blind, placebo
      controlled study.
AB  - OBJECTIVE: Depersonalization disorders (DPDs) are highly prevalent in population.
      However, the effect of lamotrigine on outpatients with DPD without psychiatric
      comorbidity has not been studied in a double-blind placebo-controlled design.
      METHOD: Eighty patients (all men) were washed out from all medications. Each
      patient was randomized either to receive lamotrigine (40 patients) for 12 weeks
      or matched on placebo (40 patients) in a double-blind manner. Eligible
      participants, in addition to meeting the criteria for DPD from Diagnostic and
      Statistical Manual of Mental Disorders, 4th Edition, Text Revision, were required
      to be between 18 and 65 years. Response was defined as a 50% reduction in the
      Cambridge Depersonalization Scale. Response effects with lamotrigine and placebo
      were compared by using analysis of variance and chi2 tests. Six patients did not
      return for at least 1 subsequent assessment, and 74 patients dropped out (36
      taking lamotrigine and 38 taking placebo) in the valuables study group. RESULTS:
      Of the 36 lamotrigine-treated participants, 26 responded by 12 weeks versus 6 of
      the 38 placebo-treated participants (P < 0.001). The most common and problematic
      adverse effect in the lamotrigine group was rash. CONCLUSIONS: The authors
      believe this to be the first double-blind placebo-controlled randomization study
      to test the efficacy of lamotrigine in the management of outpatients with DPDs.
      These need to be replicated in a larger study group.

PMID- 21192146
TI  - Advances pertaining to the pharmacology and interactions of irreversible
      nonselective monoamine oxidase inhibitors.
AB  - Recent advances clarifying the pharmacology and interactions of irreversible
      nonselective monoamine oxidase inhibitors that have not been considered in depth
      lately are discussed. These new data elucidate aspects of enzyme inhibition and
      pharmacokinetic interactions involving amine oxidases, cytochrome P450 enzymes,
      aminotransferases (transaminases), and decarboxylases (carboxy-lyases) and the
      effects of tyramine. Phenelzine and tranylcypromine remain widely available, and
      many publications have data relevant to this review. Their effect on CYP 450
      enzymes is less than many newer drugs. Tranylcypromine only inhibits CYP 450 2A6
      (selectively and potently). Phenelzine has no reported interactions, but, like
      isoniazid, weakly and irreversibly inhibits CYP 450 2C19 and 3A4 in vitro. It
      might possibly be implicated in interactions (as isoniazid is). Phenelzine has
      some clinically relevant inhibitory effects on amine oxidases, aminotransferases,
      and decarboxylases, and it lowers pyridoxal phosphate levels. It commonly causes
      pyridoxal deficiency, weight gain, sedation, and sexual dysfunction, but only
      rarely causes hepatic damage and failure, or neurotoxicity. The adverse effects
      and difficulties with monoamine oxidase inhibitors are less than previously
      believed or estimated, including a lower risk of hypertension, because the
      tyramine content in foods is now lower. Potent norepinephrine reuptake inhibitors
      have a strong protective effect against tyramine-induced hypertension. The newly
      discovered trace amine-associated receptors probably mediate the pressor
      response. The therapeutic potential of tranylcypromine and L-dopa in depression
      and Parkinson disease is worthy of reassessment. Monoamine oxidase inhibitors are
      not used to an extent proportionate with their benefits; medical texts and
      doctors' knowledge require a major update to reflect the evidence of recent
      advances.

PMID- 21192147
TI  - Premorbid functioning and treatment response in recent-onset schizophrenia:
      prospective study with risperidone long-acting injectable.
AB  - Premorbid functioning may be associated with treatment response, but this is
      confounded by a lack of prospective longitudinal data and controls for medication
      compliance. This study tested the hypothesis that good premorbid functioning will
      be associated with better antipsychotic treatment response after controlling for
      drug adherence by using a long-acting injectable antipsychotic. This was a 6
      month, open label, multicenter, phase IV trial in recent-onset schizophrenia
      treated with flexible doses of risperidone long-acting injectable (25-50 mg every
      14 days). Premorbid functioning was assessed with the Premorbid Adjustment Scale
      (PAS)-Structured Interview; efficacy was evaluated with clinician-rated Positive
      and Negative Syndrome Scale, Clinical Global Impression scale of Severity of
      Illness, Clinical Global Impression scale of Change, Global Assessment of
      Functioning Scale, and trial participant completed SF-36. Analyses controlled for
      baseline scores and demographics. With the use of a priori PAS scoring criteria,
      the participants' premorbid functioning was categorized as stable-good (n = 142),
      stable-poor (n = 116), and deteriorating (n = 36). At baseline, the stable-good
      group had the best functioning on most efficacy measures. All groups showed
      significant improvement on efficacy measures with treatment. Improvement was
      significantly higher for the stable-good group. The PAS global assessment of
      highest level of functioning scale (excellent, n = 75; good, n = 117; fair, n =
      78; and poor, n = 31) showed a strong association with baseline functioning and
      improvement and had a significant linear association with meeting Remission in
      Schizophrenia Working Group symptom criteria at baseline (P = 0.003) and attained
      and sustained remission for 3 months during study (47.7%, 49.3%, 29.6%, and
      22.2%; P = 0.006). Good premorbid functioning corresponds with better treatment
      response in recent-onset psychosis as captured on both clinician and patient
      reported measures.

PMID- 21192148
TI  - The role of the family and improvement in treatment maintenance, adherence, and
      outcome for schizophrenia.
AB  - INTRODUCTION: In the context of a large, random assignment, controlled study
      evaluating the relative effectiveness and safety of antipsychotic medication
      (CATIE), we examined the relationship between treatment outcome and 2 family
      variables: their presence and their ability to support treatment adherence.
      METHODS: Post hoc, we assessed the 50 study patients (40 of whom had families)
      and their families by dividing them into 2 groups. The first had a
      family/significant other, available and mostly supportive, to work
      collaboratively on adherence with the treatment team (n = 27). The second group
      either did not have the family/significant other or, if they did, lacked support
      for long-term maintenance (n = 23). Next, we examined outcome on 2 measures:
      study completion (vs discontinuation) and global outcome. RESULTS: Of 27 patients
      with available/supportive families, 23 remained in treatment for the full study
      course. In contrast, 13 of 23 patients, who were discontinued or dropped out,
      either did not have families or, if they had them, were unable to support
      adherence (P < 0.01). As to global outcome, 24 of the 27 patients who had
      supportive families improved, compared with only 9 of the 23 of the other group
      (P < 0.001). DISCUSSION: In summary, in the context of a large medication
      efficacy-effectiveness trial, we present data suggesting that having a "family"
      available and supportive (regardless of the interpersonal issues between patient
      and family) improves outcome mediated by improving long-term adherence.

PMID- 21192149
TI  - Effects of the cannabinoid-1 receptor antagonist rimonabant on psychiatric
      symptoms in overweight people with schizophrenia: a randomized, double-blind,
      pilot study.
AB  - Weight gain is a major adverse effect of several second-generation antipsychotic
      medications. Rimonabant is a cannabinoid-1 receptor antagonist that promotes
      weight loss in the general population. We conducted a 16-week, double-blind,
      placebo-controlled study of rimonabant (20 mg/d) in people with schizophrenia or
      schizoaffective disorder, based on the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition criteria, who were clinically stable on second
      generation antipsychotics. Participants had a body mass index of 27 kg/m or
      higher with hyperlipidemia or body mass index of 30 kg/m or higher, and no
      current substance abuse/dependence (except nicotine), more than weekly cannabis
      use, or recent depressive symptoms/suicidality. An exercise and dietary
      counseling group was offered weekly. Target enrollment was 60; the trial was
      terminated early because of withdrawal of rimonabant from the European market.
      Fifteen participants were randomized (7 rimonabant, 8 placebo); 5 completed in
      each group. Rimonabant was associated with a greater reduction in Brief
      Psychiatric Rating Scale total score versus placebo (mean +/- SE difference, -1.9
      +/- 0.8, P = 0.02), driven by differences in the Brief Psychiatric Rating Scale
      anxiety/depression (-1.4 +/- 0.35, P = 0.0004) and hostility (-0.7 +/- 0.3, P =
      0.02) factors. Group differences were not significant for the Calgary Depression
      Scale total score (P = 0.24), Scale for the Assessment of Negative Symptoms total
      score (P = 0.13), weight, blood pressure, or fasting lipids or glucose.
      Rimonabant was well tolerated with no significant adverse events. No significant
      weight loss, metabolic effects, or adverse psychiatric effects were associated
      with the cannabinoid-1 receptor antagonist rimonabant in this small sample of
      people with schizophrenia. The endocannabinoid system remains a promising target
      for pharmacotherapy of schizophrenia and obesity.

PMID- 21192151
TI  - Antidepressant drugs in children and adolescents: analytical and demographic data
      in a naturalistic, clinical study.
AB  - Pharmacokinetics of antidepressant drugs (ATDs), in terms of steady-state and
      trough values, in patients from Child and Adolescent Psychiatry centers in the
      midsouth-eastern part of Sweden, were evaluated, and the use of ATDs in this
      population were described. Patients to be prescribed an ATD were studied between
      2002 and 2004. Two hundred eleven children, 64% girls and 36% boys (ages 8-20
      years) were evaluated. The primary indication for the antidepressant treatment
      was depression in 69% of subjects. The median body mass index was 20.2 kg/m2
      (range, 12.4-38.6 kg/m2). Suspected adverse drug reactions were spontaneously
      reported in 31% (no serious). Monotherapy was indicated in 49% of request forms.
      The most common drug combination with the ATD was oral contraceptives. The
      concentrations of drugs in the patient evaluated population to referenced data
      for adults from the dose administered were as expected in 63%, higher than
      expected in 26% and lower than expected in 11%. The most prescribed ATD was
      sertraline (SERT). Dose-concentration relationships for SERT and metabolite
      desmethylsertraline (DSERT) were seen, rs = 0.48 and rs = 0.5, respectively. No
      relationship was found between dose and ratio DSERT/SERT. The median daily dose
      was 50 mg (range, 12.5-150 mg), SERT concentration 16 ng/mL (range, 3-88 ng/mL),
      and DSERT 33 ng/mL (range, 0-253 ng/mL). CYP2D6*4 was the most common poor
      metabolizer allele. Therapeutic drug monitoring may provide support to
      prescribing physicians to individual dose optimizing and to assess drug
      compliance, above all when ATDs are not well studied in pediatric patients before
      approval for general prescription.

PMID- 21192150
TI  - Antidepressant exposure as a predictor of clinical outcomes in the Treatment of
      Resistant Depression in Adolescents (TORDIA) study.
AB  - This paper examines the relationship between plasma concentration of
      antidepressant and both clinical response and adverse effects in treatment
      resistant depressed adolescents. Adolescents (n = 334) with major depression who
      had not responded to a selective serotonin reuptake inhibitor (SSRI) were
      randomized to 1 of 4 treatments: switch to another SSRI (fluoxetine, citalopram,
      or paroxetine), switch to venlafaxine, switch to SSRI plus cognitive behavior
      therapy, or switch to venlafaxine plus cognitive behavior therapy. Adolescents
      who did not improve by 6 weeks had their dose increased. Plasma concentrations of
      medication and metabolites were measured at 6 weeks in 244 participants and at 12
      weeks in 204 participants. Adolescents treated with citalopram whose plasma
      concentration was equal to or greater than the geometric mean (GM) showed a
      higher response rate compared to those with less than the GM, with parallel but
      nonsignificant findings for fluoxetine. A dose increase of citalopram or
      fluoxetine at week 6 was most likely to result in response when it led to a
      change in concentration from less than the GM at 6 weeks to the GM or greater at
      week 12. Plasma levels of paroxetine, venlafaxine, or O-desmethylvenlafaxine were
      not related to clinical response. Exposure was associated with more
      cardiovascular and dermatologic side effects in those receiving venlafaxine.
      Antidepressant concentration may be useful in optimizing treatment for depressed
      adolescents receiving fluoxetine or citalopram.

PMID- 21192152
TI  - Pseudohypoalgesia on the skin: a novel view on the paradox of pain perception in
      depression.
AB  - Previous studies reported increased heat pain thresholds and decreased ischemic
      pain thresholds in patients experiencing depression. The increased sensitivity to
      ischemic muscle pain was assumed to represent a model for the investigation of
      physical symptoms in the disease. Here, we explored how the serotonin and
      noradrenaline reuptake inhibitor duloxetine influences experimental pain
      thresholds and tolerances in depressed patients during treatment. Twenty-two
      patients experiencing unipolar depression were included. Pain assessments were
      conducted unmedicated at baseline, after 1 week, and after 6 weeks of duloxetine
      treatment. We observed the expected clinical response of patients indicated by a
      significant reduction in the Montgomery Depression Rating Scale after 6 weeks. At
      baseline, we found increased heat pain thresholds in patients in comparison to
      controls while patients simultaneously rated augmented pain perception on the
      visual analog scale. In contrast, patients were significantly more perceptive to
      ischemic muscle pain at baseline. During treatment, the examined pain thresholds
      showed differential changes: Increased heat pain thresholds of patients
      normalized during treatment, whereas no significant change was observed for
      ischemic pain thresholds. Thus, our results might change the view on the paradox
      of pain perception in major depression because increased heat pain thresholds are
      associated with augmented pain perception in the disease.

PMID- 21192153
TI  - Long-term safety of OROS methylphenidate in adults with attention
      deficit/hyperactivity disorder: an open-label, dose-titration, 1-year study.
AB  - OBJECTIVE: To evaluate the long-term safety of OROS methylphenidate in the
      management of attention-deficit/hyperactivity disorder (ADHD) in adults. METHODS:
      This multicenter, open-label, dose-titration, flexible dose study enrolled adults
      with ADHD for 6 or 12 months of treatment with OROS methylphenidate. Dosing began
      at 36 mg/d, with titration in 18-mg increments every 7 days until a predefined
      outcome (efficacy threshold, maximum dosage of 108 mg/d, or limiting adverse
      event). Dose reduction occurred for prespecified reasons, and the subjects
      discontinued if unable to tolerate 36 mg/d. Assessments included ADHD symptoms,
      adverse events, vital signs, and laboratory results. RESULTS: A total of 550
      subjects received treatment (52% were men; mean age, 39 years; range, 18-65
      years), and 57% (146/258) and 44% (129/292) completed their 6 or 12 months of
      treatment with mean durations of 128 and 213 days, respectively. The final
      prescribed dosages were 36 mg/d (22.4%), 54 mg/d (25.1%), 72 mg/d (22.0%), 90
      mg/d (17.1%), and 108 mg/d (13.5%). Modest increases from baseline to final visit
      were observed in mean systolic (2.6 mm Hg) and diastolic (1.9 mm Hg) blood
      pressure and pulse (4.1 beats per minute). The mean weight decreased by 2.3 kg.
      No clinically meaningful changes in laboratory values or electrocardiogram
      parameters were observed other than increased heart rate. Most common adverse
      events included decreased appetite (26.7%), headache (24.0%), and insomnia
      (20.7%). No serious adverse event was considered related to study medication.
      Several measures of efficacy indicated improvement during the study. CONCLUSIONS:
      OROS methylphenidate, in the flexible dosage range from 36 to 108 mg/d, was well
      tolerated for up to 1 year in adults with ADHD.

PMID- 21192154
TI  - The impact of dosage of sustained-release formulation on valproate clearance and
      plasma concentration in psychiatric patients: analysis based on routine
      therapeutic drug monitoring data.
AB  - Pharmacokinetic parameters were compared between 2 dosages of valproic acid (VPA)
      sustained-release (SR) formulation in psychiatric patients. A total of 66
      psychiatric patients (21 women and 45 men; age range, 18-60 years) receiving 500
      mg/d (n = 28) or 1000 mg/d (n = 38) of VPA SR for at least 4 weeks were recruited
      into the study. A 5-mL blood sample was collected into a plain tube and
      immediately centrifuged for plasma. Separation of free VPA was further done using
      Centrifree micropartition devices. Both total and free VPA concentrations
      (C(total) and C(free)) were analyzed by TDx analyzer with fluorescence
      polarization immunoassay technique. The patients' characteristics and
      pharmacokinetic parameters were compared between the 2 dosage groups using
      independent t test or chi2 test where appropriate. The results show that the
      increment in C(total) (mg/mL) for every milligram-per-kilogram increment in
      dosage was decreased from 7 +/- 3 to 4 +/- 1 (mg/L) / (mg/kg) when the total VPA
      clearance (CL(total)) increased from 6.1 +/- 2.6 to 9.0 +/- 3.1 mL/kg per hour
      with the increasing dose in the 500 mg/d and 1000 mg/d groups, respectively (P <
      0.05). The increment in C(free) [0.6 +/- 0.3 vs 0.5 +/- 0.2 (mg/L) / (mg/kg)] and
      CL(free) (80.4 +/- 41.5 vs 92.2 +/- 47.6 ml/kg per hour) were not significantly
      different. Owing to the saturation of protein binding, percent free VPA was
      significantly increased from 8 +/- 3 to 11 +/- 3 when the dose was increased from
      500 to 1000 mg/d (P < 0.05). In conclusion, an increase in the VPA dose resulted
      in a disproportional increase between dosage and C(total), whereas a proportional
      increase between dosage and C(free) still existed. Therefore, our study suggests
      that the therapeutic range of C(free) is 4 to 12 mg/L based on the therapeutic
      range of C(total) (45-100 mg/L) for general psychiatric conditions.

PMID- 21192155
TI  - Effectiveness of quetiapine in outpatients with schizophrenia assessed under
      "real-life" conditions: a German clinical-practice evaluation programme.

PMID- 21192156
TI  - Erroneous administration of clozapine in a very elderly patient.

PMID- 21192157
TI  - The impact of hospital smoking ban on clozapine and norclozapine levels.

PMID- 21192158
TI  - Preliminary report: a naturalistic study of the effect of aripiprazole addition
      on risperidone-related hyperprolactinemia in patients treated with risperidone
      long-acting injection.

PMID- 21192159
TI  - Micturition difficulty associated with aripiprazole: report of 2 cases.

PMID- 21192160
TI  - A case report of risperidone distribution and excretion into human milk: how to
      give good advice if you have not enough data available.

PMID- 21192161
TI  - Risperidone reduces tic-like motor behaviors and linguistic dysfluencies in
      severe persistent developmental stuttering.

PMID- 21192162
TI  - Aripiprazole-associated bruxism, akathisia, and parkinsonism in a bipolar
      patient.

PMID- 21192163
TI  - Potential control of risperidone-related cognitive deficits by adjunctive
      aripiprazole treatment.

PMID- 21192165
TI  - Oxcarbazepine-related thrombocytopenic purpura.

PMID- 21192166
TI  - Very-low-dose topiramate for anger control: three cases.

PMID- 21192167
TI  - Efficacy and safety of gamma-hydroxybutyrate in treating alcohol withdrawal
      syndrome in an alcohol-dependent inpatient with decompensated liver cirrhosis: a
      case report.

PMID- 21192168
TI  - Evaluation of p16INK4a immunohistochemical reactivity in endocervical glandular
      neoplasia.
AB  - OBJECTIVE: To determine the expression of p16INK4a by immunohistochemistry in
      endocervical neoplasms. METHODS: Forty-nine cases of endocervical glandular
      neoplasia were identified by record review. On histopathologic review of the
      original and new slides, 16 cases were identified as endocervical adenocarcinoma
      in situ (AIS), 31 were identified as invasive adenocarcinoma, and 2 had no
      remaining tumor identified. A representative paraffin block was selected from
      each case with tumor and sections cut from each block. One section from each case
      was stained with hematoxylin and eosin, 1 was processed for immunohistochemical
      study for p16INK4a, and 1 was a negative control. The nuclear immunoreactivity
      was graded positive, indeterminate, or negative. RESULTS: Cases were classified
      AIS, adenocarcinoma, or no tumor. Of 16 cases of AIS, 15 (93.01%) cases were
      immunoreactive to p16INK4a; 1 case was negative. All cases of invasive
      adenocarcinoma, 31 of 31 cases (100%), were immunoreactive to p16INK4a.
      CONCLUSIONS: p16INK4a reactivity can be used to help identify and assess in situ
      and invasive endocervical glandular neoplasms.

PMID- 21192169
TI  - ProExC triage of atypical glandular cells on liquid-based cervical cytology
      specimens.
AB  - OBJECTIVE: Morphologic distinction between atypical glandular cells not otherwise
      specified (AGC-NOS) and AGC-favor neoplasia (AGC-FN) can be difficult.
      Distinction between these entities is important as the American Society for
      Colposcopy and Cervical Pathology 2006 consensus guidelines state that management
      of AGC-NOS differs from that of AGC-FN. The objective of this study was to
      determine the potential role of ProExC immunocytochemical triage of AGC-NOS.
      MATERIALS AND METHODS: Cytopathology records from a pathology practice were
      reviewed from January 2006 to December 2009 to identify AGC-NOS liquid-based Pap
      smears with subsequent biopsy correlation. Archival slides were examined, and
      ProExC immunocytochemistry was performed. The AGC groups were assessed for
      nuclear staining, and results were correlated with subsequent biopsy findings.
      RESULTS: Twenty-eight AGC-NOS cases with biopsy correlation were identified: 13
      with subsequent high-grade neoplastic or malignant (positive) diagnoses and 15
      with benign diagnoses. Of 13 AGC-NOS cases with positive diagnosis, 10 were
      ProExC-positive and 3 were ProExC-negative (metastatic tumors from distant
      sites). Of 15 AGC cases with benign follow-up, 13 were ProExC-negative and 2 were
      ProExC-positive (sensitivity, 77%; specificity, 87%). For patients with cervical
      intraepithelial neoplasia or carcinoma originating from the female genital tract,
      100% (10/10) were ProExC-positive (sensitivity, 100%; specificity, 87%).
      CONCLUSIONS: Results suggest that ProExC-positive AGC-NOS may be classified as
      AGC-FN. Although positive immunocytochemical staining for ProExC requires
      management similar to AGC-FN, negative staining does not rule out malignancy such
      as metastatic tumor. Management for ProExC-negative AGC-NOS cases should proceed
      according to the current guidelines for AGC-NOS.

PMID- 21192170
TI  - Risk of cervical intraepithelial neoplasia 2+ among women with a history of
      previous treatment for cervical intraepithelial neoplasia: ASCUS and LSIL Pap
      smears after treatment.
AB  - OBJECTIVE: The objective of the current study was to describe outcomes among
      women with low-grade abnormalities on cervical cytology screening in the setting
      of previous excisional or ablative treatment for cervical intraepithelial
      neoplasia (CIN). METHODS: Study participants were recruited into the Study to
      Understand Cervical Cancer Early Endpoints and Determinants. At enrollment, the
      patient's previous cytology results, previous colposcopic biopsy results, and
      previous cervical procedures were recorded. Study procedures included collection
      of biospecimens followed by colposcopy and biopsy. From clinical records,
      additional information regarding previous treatment for CIN was collected.
      RESULTS: Two hundred seventy-four women had an atypical squamous cells of
      uncertain significance (ASCUS) referral Pap and 532 women had a low-grade
      squamous intraepithelial lesion (LSIL) referral Pap. For patients with an ASCUS
      referral Pap, previous treatment was associated with an odds ratio for CIN 2+
      (45.0% vs 28.2% of untreated patients) of 2.08 (95% confidence interval = 1.05
      4.13, p = .04). For patients with an LSIL referral Pap, 33.3% of those women with
      previous treatment had CIN 2+ compared with 16.7% of those patients enrolled with
      no previous treatment (odds ratio = 2.49, 95% confidence interval = 1.12-5.51, p
      = .03). CONCLUSIONS: Patients with a history of previous treatment for CIN have a
      2-fold risk of CIN 2+ at the time of colposcopy referral for ASCUS or LSIL
      cervical cytology.

PMID- 21192171
TI  - Clinical and pathologic features of vulvar intraepithelial neoplasia in
      premenopausal and postmenopausal women.
AB  - OBJECTIVE: To explore the clinical and pathologic differences between vulvar
      intraepithelial neoplasia (VIN) in premenopausal and postmenopausal women cared
      for in a tertiary referral center. METHODS: Between January 1997 and June 2008,
      145 women received care at our institution for VIN and VIN-associated squamous
      cell carcinoma (SCC). All patients' demographic characteristics and recurrence
      histories were recorded throughout the study period and were retrieved
      retrospectively. Menopausal status was self-reported at the time of initial
      diagnosis. chi, odds ratio, and logistic regression analyses were used. RESULTS:
      The median age was 50 years (range = 19-91 y) with 77% (111/145) of patients
      white, 20% (29/145) African American, and 3% (5/145) other ethnicity. Sixty
      percent of patients diagnosed with VIN were current smokers, 18% (26/145) were
      immunocompromised (positive for human immunodeficiency
      virus/transplant/steroids), and 30% (44/145) had concomitant or previous lower
      genital tract dysplasia. Vulvar intraepithelial neoplasia or VIN-related cancer
      recurred in 57 (39%) of 145 patients; of these, 40 (71%) had recurrence of VIN
      and 18 (29%) had recurrence of cancer. Fifty-one percent (74/145) of patients
      were menopausal at initial VIN diagnosis. Among women with VIN, the odds of
      initially presenting with a VIN-related SCC was 3.2 times greater in
      postmenopausal than in premenopausal women (confidence interval = 1.5-7.1, p <
      .01), and postmenopausal women were more likely to present with stage II to IV
      SCC (p = .021). Recurrence risk of SCC, but not VIN, was associated with
      menopause status (p < .05). CONCLUSIONS: Among women with VIN, the risk of SCC is
      higher in postmenopausal than in premenopausal women both initially and at
      recurrence. Excisional therapies to identify occult invasion are especially
      important for postmenopausal women with VIN.

PMID- 21192172
TI  - Prevalence and risk factors of Chlamydia trachomatis cervicitis in pregnant women
      at the genital tract infection in obstetrics unit care at Botucatu Medical
      School, Sao Paulo State University-UNESP, Brazil.
AB  - OBJECTIVE: To evaluate the prevalence of and risk factors for Chlamydia
      trachomatis cervicitis in pregnant women seen at the Genital Tract Infection in
      Obstetrics Unit Care in Botucatu Medical School, Sao Paulo State University -
      UNESP. MATERIALS AND METHODS: Between June 2006 and February 2008, 101 pregnant
      women were included in this study. During the gynecologic examination, cervical
      secretions were collected using cytobrush Plus GT (CooperSurgical Inc) to assess
      C. trachomatis using polymerase chain reaction. Vaginal flora were examined by
      Gram stain, and sociodemographic data were extracted from medical records.
      RESULTS: Of the 101 patients, 26 (25.7%) were positive for C. trachomatis. The
      median age of the infected group was 24 years (range = 13-40 y), and 48.5% of
      them had abnormal vaginal flora. The presence of chlamydial infection was
      associated with smoking (odds ratio [OR] = 2.67, 95% confidence interval [CI] =
      1.01-7.19), residing in a city with fewer than 100,000 inhabitants (OR = 2.86,
      95% CI = 1.03-7.94), presence of condyloma acuminatum (p = .03), and presence of
      discreet inflammation on Pap smear (p = .02). CONCLUSIONS: The prevalence of C.
      trachomatis is high in pregnant women seen at the Genital Infection Unit Care,
      UNESP, and is related to many risk factors. Therefore, its screening is extremely
      important in reducing obstetrical and neonatal complications.

PMID- 21192173
TI  - Impact of the 2002 American society for Colposcopy and Cervical Pathology
      guidelines on cervical cancer diagnosis in a geographically diverse population of
      commercially insured women, 1999-2004.
AB  - OBJECTIVE: To report the impact of the release of the 2002 American Society for
      Colposcopy and Cervical Pathology guidelines on the management of abnormal
      cytological findings on time to diagnosis of cervical cancer in an insured
      population. METHODS: This retrospective study identified women with cervical
      cancer (invasive and carcinoma in situ) through commercially insured
      administrative claims data. The cervical cancer case definition required a claim
      for cervical cancer and a claim with a diagnostic procedure (colposcopy,
      conization, biopsy, or hysterectomy). Time to diagnosis was defined as days
      between the initial Pap screening and the diagnostic procedure. RESULTS: Between
      1999 and 2004, there were 3,325 women aged 18 to 64 years who met the case
      definition for cervical cancer. Median time to diagnosis decreased from 42 days
      (interquartile range = 23-93 d) to 36.5 days (interquartile range = 20.5-80 d)
      for women with invasive cancer after the guideline change. The number of follow
      up Pap screenings before biopsy also decreased (p = .0067). Among women with
      carcinoma in situ whose initial Pap screening was completed by a family practice
      clinician, time to diagnosis was projected to be more than 9 days longer compared
      with those whose screening was performed by a gynecologist. CONCLUSIONS: The 2002
      American Society for Colposcopy and Cervical Pathology guidelines for the
      management of abnormal cytological findings seem to have had a positive impact on
      the time to diagnosis and Pap screening use before biopsy for women diagnosed
      with cervical cancer.

PMID- 21192174
TI  - Pathogenicity of non-albicans yeasts in the vagina.
AB  - OBJECTIVE: It is hypothesized that vaginal non-albicans yeasts (NAYs) do not
      require treatment. The objective was to determine whether women (presenting with
      a range of vulvovaginal complaints) found to be harboring NAY, which is left
      untreated (no antifungals), have similar clinical outcomes to women with
      comparable presentations but who do not harbor NAY. DESIGN: This is a case
      control study design comparing patient outcomes between women with untreated non
      albicans Candida on vaginal swab cultures and those who were swab culture
      negative. SETTING: A Melbourne metropolitan, private gynecologic and obstetric
      practice. POPULATION: Women presenting with vulvovaginal symptoms or management
      of pregnancy, who attended the above practice between 2001 and 2006. METHODS:
      Fifty-two women were found to have NAY on culture of their vaginal swabs. They
      were prospectively studied to determine the effect of leaving the NAY untreated
      (no antifungals) but with appropriate attention to their other diagnoses. Seventy
      eight symptomatic women with negative swab cultures were used as the comparison
      group, and descriptive statistics was computed to compare patient outcomes
      between the groups. A subanalysis was also carried out, only looking at women who
      presented with pruritus. MAIN OUTCOME MEASURE: Proportion of patients self
      reporting improvement in symptoms. RESULTS: Of the 44 women with NAY who
      presented with symptoms, 86% reported experiencing improvement. Approximately 77%
      of the women in the comparative group reported improvement. CONCLUSIONS: Non
      albicans yeasts found on culture of a vaginal swab can probably be ignored. The
      clinician's efforts should be concentrated on making a correct diagnosis without
      assuming that NAY are pathogenic.

PMID- 21192175
TI  - A comparison of loop electrosurgical excision procedures between human
      immunodeficiency virus-seropositive and -seronegative women.
AB  - OBJECTIVE: The purpose of this study was to compare preoperative and
      postoperative factors between human immunodeficiency virus (HIV)-seropositive and
      -seronegative women having a loop electrosurgical excision procedure (LEEP). Our
      hypothesis is that cervical intraepithelial neoplasia (CIN) presents differently
      in immunocompromised women. MATERIALS AND METHODS: A database of LEEPs performed
      from October 2004 to November 2009 at John H. Stroger Jr. Hospital, Cook County,
      Illinois, was created. Patients were considered to have persistent/recurrent
      disease if they had a cytological diagnosis of atypical squamous cells, cannot
      exclude high-grade squamous intraepithelial lesion, or worse with no histology or
      a histological diagnosis of CIN 1 or worse at any time after their LEEP. chi2
      Analysis was performed to evaluate differences between HIV-seropositive and 
      seronegative women. RESULTS: There were 886 LEEPs performed during the study
      period, 92 among HIV-seropositive and 794 among HIV-seronegative women. Overall,
      64.7% had any cytology or histology performed after their procedure, and
      seropositive women were more likely to follow up (p = .004). Preoperative
      cytological and cervical histological diagnoses were not different between
      seropositive and negative women; however, a preoperative endocervical curettage,
      which was positive, was more common among seropositive women (p < .0001). Human
      immunodeficiency virus-seropositive women were more likely to have CIN on LEEP
      histology (p = .04), and more likely to have positive margins (p < .0001) and
      recurrent/persistent disease (p < .0001). CONCLUSIONS: The spectrum of cervical
      disease was very different between HIV-seropositive and -negative women having
      LEEPs in our study. Practitioners managing HIV-infected women should be aware of
      these differences and counsel and follow up appropriately.

PMID- 21192176
TI  - Effect of stress and depression on the frequency of squamous intraepithelial
      lesions.
AB  - OBJECTIVE: To explore the previously reported associations between cervical
      squamous lesions and psychologic measures of stress and depression. METHODS: In a
      multicenter cohort study, women with HIV and HIV-seronegative women had Pap tests
      and completed self-report questionnaires including the Perceived Stress Scale-10
      (PSS), which measures perceived stress, the Posttraumatic Stress Disorder (PTSD)
      Checklist-Civilian Version (PCL-C), which measures symptoms of PTSD, and the
      Center for Epidemiologic Studies Depression (CES-D) scale, which measures
      depressive symptoms. RESULTS: Median scores were 13 (range = 0-38) for the PSS,
      24 (range = 17-85) for the PCL-C, and 8 (range = 0-57) for the CES-D, indicating
      moderate stress and minimal depression. For PSS, compared with women in the
      lowest tertile of reported stress, the odds ratios (ORs) for squamous
      intraepithelial lesions (SIL) were 0.88 (95% confidence interval [CI] = 0.50
      1.54) for women in the middle tertile and 0.96 (95% CI = 0.54-1.68) for women in
      the highest tertile. For PCL-C, compared with women in the lowest tertile of PTSD
      symptoms, ORs for SIL were 0.79 (95% CI = 0.43-1.41) for women in the middle
      tertile and 1.17 (95% CI = 0.68-2.01) for women in the highest tertile. Rates of
      SIL were similar for CES-D scores 16 or higher (compared with women with lower
      scores; OR = 1.41, 95% CI = 0.88-2.26) and 23 or higher (OR = 1.39, 95% CI = 0.81
      2.40). In the multivariable analysis including the number of sexual partners,
      age, income, ethnicity, and serostatus, stress as measured by PSS and PCL-C and
      depressive symptoms as measured by CES-D remained unassociated with SIL.
      CONCLUSIONS: We found no evidence that stress and depression affect the
      prevalence of cervical squamous lesions.

PMID- 21192177
TI  - Human papillomavirus infection in Honduran women with cervical intraepithelial
      neoplasia or cervical cancer.
AB  - OBJECTIVES: The aims of this study were to investigate human papillomavirus (HPV)
      genotypes in women with cervical intraepithelial lesions and cervical cancer (CC)
      in Honduras and to identify epidemiological cofactors that contribute to the
      development of CC. METHODS: Among the 289 patients analyzed, 139 had low-grade
      squamous intraepithelial lesion (LSIL), 60 had high-grade squamous
      intraepithelial lesion (HSIL), and 90 had CC. RESULTS: The HPV DNA was detected
      in 113 women (81%) with LSIL, in 58 women (97%) with HSIL, and in 84 women (93%)
      with CC. Twenty-five HPV genotypes were found. Human papillomavirus type 16 was
      detected in 41% of women with CC, in 35% of women with HSIL, and in 24% of women
      with LSIL. Human papillomavirus type 18 was found in 9% of women with CC, in 4%
      of women with HSIL, and 5% of women with LSIL. CONCLUSION: Therefore,
      implementation of the prophylactic vaccines against HPV genotypes 16 and 18 has
      the potential of preventing at least a quarter of LSIL, one third of HSIL, and
      about half of CC cases in Honduras.

PMID- 21192178
TI  - Risk of cervical precancer and cancer in women aged 30 years and older with an
      HPV-negative low-grade squamous intraepithelial lesion screening result.
AB  - OBJECTIVE: To characterize the 6- and 18-month cumulative risk of cervical
      intraepithelial neoplasia grade 2 or worse (CIN 2+) and grade 3 or worse (CIN 3+)
      in women aged 30 years and older after a low-grade squamous intraepithelial
      lesion (LSIL) cytology and high-risk human papillomavirus (HPV)-negative
      screening result in routine clinical practice. MATERIALS AND METHODS:
      Comprehensive quality assurance databases of screening test and biopsy results
      from the Regional Laboratory of the Kaiser Permanente Northern California Health
      Plan were reviewed. All women aged 30 years and older with LSIL cytology were
      sorted by high-risk HPV status. Associated biopsy results were tabulated, and the
      corresponding risks of CIN 2+ and CIN 3+ diagnosed within 18 months after LSIL
      cytology were calculated overall and by decade of age. RESULTS: During the 6-year
      period, from 2003 to 2008, 4,113 LSIL cases were interpreted in women aged 30
      years and older for which corresponding high-risk HPV and biopsy results were
      available. The proportion of women with LSIL testing positive for HPV declined
      with age, from 89% in the group aged 30 to 39 years to 76% in women older than 50
      years (p < .001). Of 622 women with HPV-negative LSIL cytology, there was no case
      of cancer detected at colposcopy occurring within 6 months of the screening test.
      The 18-month risks of CIN 2+ and CIN 3+ were 3.5% and 1.4%, respectively.
      CONCLUSIONS: The risk of CIN 3+ is sufficiently low in women aged 30 years and
      older with high-risk HPV-negative LSIL that 1 year follow-up rather than
      immediate colposcopy should be considered when it occurs in routine clinical
      practice.

PMID- 21192179
TI  - Papular colpitis: a distinct clinical entity? Symptoms, signs, histopathological
      diagnosis, and treatment in a series of patients seen at the Rotterdam vulvar
      clinic.
AB  - OBJECTIVE: To study demographic, clinical, and histopathological data as well as
      treatment outcome in women with papular colpitis. MATERIALS AND METHODS: Data of
      women (n = 18) visiting the Rotterdam vulvar clinic and meeting the diagnostic
      criteria for papular colpitis were retrospectively analyzed using patient
      records. RESULTS: Papular colpitis is usually seen in perimenopausal women and is
      frequently associated with copious, nonoffensive vaginal discharge and
      dyspareunia. Histopathological diagnosis consistently shows dense lymphocytic
      infiltrates. In approximately half of the women, the vulva shows Zoon-like
      abnormalities. Treatment with topically applied 10% hydrocortisone acetate seemed
      to be moderately effective. CONCLUSIONS: Papular colpitis seems to be a distinct,
      relatively rare and possibly autoimmune-related condition. Treatment with 10%
      hydrocortisone acetate may have a dramatic effect, but recurrences are common and
      long-term follow-up is warranted.

PMID- 21192180
TI  - Pseudoepitheliomatous hyperplasia mimicking vulvar cancer in a patient with AIDS.
AB  - BACKGROUND: Pseudoepitheliomatous hyperplasia (PEH) clinically and histologically
      mimics squamous cell carcinoma (SCC), specifically in patients with HIV and AIDS.
      CASE: A 51-year-old G3P2 with AIDS and history of vulvar cancer presented with
      large bilateral exophytic lesions on the vulva, grossly appearing neoplastic.
      Initial biopsies of the lesions were interpreted as vulvar SCC. After resolution
      with empiric treatment with acyclovir for possible herpes simplex virus type 2
      outbreak, additional slides were reviewed, and cells with viral inclusions were
      identified, making the final diagnosis PEH in association with herpes simplex
      virus type 2 infection. CONCLUSIONS: Although PEH is infrequently encountered,
      PEH should be considered in the differential diagnosis of vulvar lesions. A
      multidisciplinary approach including the gynecologist, pathologist, and
      infectious disease specialists can optimize patient outcome.

PMID- 21192181
TI  - Recurrent hypertrophy of the labia minora: a hormonally related lesion possibly
      related to fibroepithelial stromal polyps of the vulva.
AB  - The literature on hypertrophy of the labia minora has focused predominantly on
      surgical procedures, with little attention to etiology. We present a case of
      recurrent labial hypertrophy and postulate that this is a hormonally related
      lesion, similar to fibroepithelial stromal polyps.

PMID- 21192182
TI  - Vaginal agglutination: chronic graft-versus-host disease mimics lichen planus.
AB  - BACKGROUND: Graft-versus-host (GVH) disease is a common problem in transplant
      patients, whereas vulvovaginal gingival syndrome is an uncommon and severe
      variant of lichen planus characterized by erosions of characteristic mucosal
      surfaces, with frequent vaginal involvement, resulting in scarring or stricture
      formation. Both conditions have the potential to present with similar clinical
      pictures. CASE: We report the history, evaluation, and treatment of a woman who
      had recently undergone stem cell transplant for acute lymphoblastic leukemia who
      presented with vaginal agglutination. A clinical diagnosis of erosive lichen
      planus versus chronic GVH disease was considered. CONCLUSIONS: Lichen planus and
      GVH disease are both inflammatory processes, which can present with a range of
      clinical conditions. Each may result in the development of irritative symptoms
      and erosive lesions on mucosal surfaces. Although lichen planus is a well-defined
      dermatosis, GVH disease is an iatrogenic process. We report the case history of a
      patient with erosive vulvovaginal lesions with scarring, likely caused by GVH
      disease, which mimicked erosive vulvovaginal lichen planus. Although the clinical
      presentation and treatment of these 2 entities are similar, this case
      demonstrates the subtle diagnostic difference between the 2 diseases.

PMID- 21192184
TI  - Vascular vertigo: epidemiology and clinical syndromes.
AB  - BACKGROUND: vertigo is a common complaint in medicine. The most common causes of
      vertigo are benign paroxysmal positional vertigo, vestibular neuritis, Meniere's
      syndrome, and vascular disorders. Vertigo of vascular origin is usually limited
      to migraine, transient ischemic attacks, and ischemic or hemorrhagic stroke.
      Vascular causes lead to various central or peripheral vestibular syndromes with
      vertigo. This study provides an overview of epidemiology and clinical syndromes
      of vascular vertigo. REVIEW SUMMARY: vertigo is an illusion of movement caused by
      asymmetrical involvement of the vestibular system by various causes. Migraine is
      the most frequent vascular disorder that causes vertigo in all age groups.
      Vertigo may occur in up to 25% of patients with migraine. The lifetime prevalence
      of migrainous vertigo is almost 1%. Cerebrovascular disorders are estimated to
      account for 3% to 7% of patients with vertigo. Vestibular paroxysmia has been
      diagnosed in 1.8% to 4% of cases in various dizziness units. Vasculitic disorders
      are rare in the general population, but vertigo may be seen in almost up to 50%
      of patients with different vasculitic syndromes. CONCLUSIONS: migraine,
      cerebrovascular disorders especially involving the vertebrobasilar territory,
      cardiocirculatory diseases, neurovascular compression of the eighth nerve, and
      vasculitis are vascular causes of vertigo syndromes.

PMID- 21192183
TI  - Fibroadenoma of the vulva--simultaneous with breast fibroadenomas and uterine
      myoma.
AB  - PURPOSE: To present a rare case of multiple fibroadenomas in breast and vulva and
      myomas in the uterus. In addition, to show the usefulness of receptor detection
      as a basis for the indication of antiestrogens. CASE: A 30-year-old patient
      presenting with a history of mammary fibroadenomas since the age of 16 years and
      uterine myomas since the age of 25 years. From age 26 to 29 years, she was
      operated on 3 times for fibroadenomas of the vulva. On the third time, she
      presented with 8 vulvar fibroadenomas. On this last occasion, a low expression of
      estrogen receptors was identified, together with a high expression of
      progesterone receptors (ER/PR pharmDx; Dako). Tamoxifen was indicated at 10 mg/d
      during the luteal phase of the menstrual cycle for 12 months. After 18 months
      from initiation of the treatment, the patient was found free of tumors in the
      vulva, with mammary tumor regression and a nonhomogeneous diffuse uterine
      myometrium. CONCLUSIONS: The presence of solid benign-type tumors in the vulva
      associated with mammary fibroadenomas and uterine myomas leads one to suspect the
      fibroadenomas. The histopathological diagnosis and the identification of the
      hormonal receptors are important for control purposes and therapeutic
      indications.

PMID- 21192185
TI  - Newly suggested surgical method of decompressive craniectomy for patients with
      middle cerebral artery infarction.
AB  - OBJECTIVES: the purpose of this study is to suggest the landmarks for
      decompressive craniectomy so that surgery can be standardized to achieve adequate
      decompression in patients with malignant middle cerebral artery infarction. We
      also analyzed the efficacy and safety of this newly suggested surgical method.
      METHODS: eleven patients (group A) underwent this newly suggested decompressive
      surgery. The bony landmarks for decompressive craniectomy are described. The area
      of the bone flap and the brain volume protruding out of the skull surface were
      measured. The outcomes were evaluated 3 months after the surgery. All the results
      were compared with that of 13 patients (group B) who were treated with
      conventional surgical methods. RESULTS: the mean area of craniectomy was larger
      in group A (399.9 +/- 50.9 cm) than that in group B (308.5 +/- 50.5 cm, P=0.021).
      The brain volume protruding out of the skull surface was 161.8 +/- 101.7 cm in
      group A and 106.3 +/- 55.1 cm in group B, indicating that more decompression was
      performed in group A (P=0.034). Six (54.5%) of 11 patients in group A had
      favorable outcomes (modified Rankin Scale 0 to 3) without mortality, whereas 2
      (15.4%) of 13 patients in group B had favorable outcomes and 3 (23.1%) patients
      in group B expired. CONCLUSION: decompressive craniectomy using the newly
      suggested method is feasible and safe, and it may be more beneficial, compared
      with conventional craniectomy, for patients with malignant middle cerebral artery
      infarction. Furthermore, it may be easier to perform by training neurosurgeons.

PMID- 21192186
TI  - Ischemic stroke in young adults: risk factors, subtypes, and prognosis.
AB  - BACKGROUND: ischemic strokes occurring in patients younger than 47 years is a
      relatively rare event and accounts for less than 5% of all ischemic strokes in
      western countries. OBJECTIVE: the etiologic spectrum in younger patients and
      older patients differs considerably. METHODS: in this hospital case series study,
      we enrolled 192 patients with ischemic stroke, aged 18 to 47 years, all of whom
      were submitted to a diagnostic protocol. The risk factors for stroke and the
      distribution of stroke subtype and prognosis were studied. Modified diagnostic
      criteria adopted from the Trial of ORG 10172 in Acute Stroke Treatment and the
      Baltimore-Washington Cooperative Young Stroke Study, were used for etiologic
      classification. RESULTS: hypertension was found to be the main risk factor (45%)
      followed by cigarette smoking (37%), hyperlipidemia (35.4%), diabetes mellitus
      (17%), and family history of stroke (18%). Hypertension, diabetes mellitus,
      hypercholesterolemia, and smoking were present either alone or in combination in
      the majority of our patients. Oral contraceptives were being taken by 25% of the
      women. The etiology of stroke was as follows: atherothrombosis 26.5%,
      cardioembolism 20%, nonatherosclerotic vasculopathies 13%, other determined
      causes 10%, lacunar stroke 6%, migraine 3.6%, and undetermined causes 21%.
      CONCLUSIONS: hypertension, diabetes mellitus, hypercholesterolemia, and smoking
      were the most common risk factors in our ischemic stroke patients between 18-47
      years of age. Health care programs targeting the prevention and treatment of
      these factors will reduce the associated morbidity and mortality of stroke among
      this socioeconomically active age group.

PMID- 21192188
TI  - Acute brachial diplegia due to Lyme disease.
AB  - OBJECTIVE: to describe acute brachial diplegia as the initial manifestation of
      Lyme disease. BACKGROUND: bilateral, predominantly motor, cervical radiculoplexus
      neuropathy, the "dangling arm syndrome," has not been reported as a complication
      of acute Lyme infection. METHODS: retrospective series of 5 patients from 2
      tertiary neuromuscular centers. RESULTS: there were 4 men and 1 woman with an
      average age of 69 years. One recalled a tick bite, and preceding constitutional
      symptoms included headache (2) and fever, arthralgias, and fatigue in 1 patient
      each. Proximal arm weakness and acute pain developed within 3 weeks from onset;
      pain was bilateral in 3 patients and unilateral in 2 patients, and was described
      as severe throbbing. Arm weakness was bilateral at onset in 3 patients, and right
      sided in 2 patients followed by spread to the left arm within days. All the
      patients had weakness in the deltoid and biceps that was 3/5 or less (Medical
      Research Council scale), with variable weakness of the triceps and wrist
      extensors; 1 patient had a flail right arm and moderate (4/5) weakness of the
      proximal left arm muscles. Light touch was normal in the regions of weakness, and
      1 patient had mildly reduced pin sensation over the forearm. Serum IgM Lyme
      titers were elevated in all the patients and were detected in the cerebrospinal
      fluid in 4 tested patients. The cerebrospinal fluid protein ranged between 135
      and 176 mg/dL with lymphocytic pleocytosis (range, 42 to 270 cells).
      Electrodiagnostic studies showed normal median and ulnar motor potentials with
      asymmetrically reduced sensory amplitudes in the median (4), ulnar (3), and
      radial, and lateral antebrachial cutaneous potentials in 1 patient each. Two
      patients had acute denervation in the cervical or proximal arm muscles. There was
      full recovery after antibiotic therapy in 4 patients and considerable improvement
      in 1 patient after 2 months. CONCLUSION: acute brachial diplegia is a rare
      manifestation of acute Lyme infection and responds promptly to antibiotic
      therapy.

PMID- 21192187
TI  - Influence of height on the clinical characteristics and prognosis of patients
      with ischemic stroke.
AB  - BACKGROUND: large, long-term population data indicate an inverse association for
      adult height with stroke incidence and mortality, whereas the risk of atrial
      fibrillation appears greater in taller individuals. However, it is unclear
      whether knowledge of an individual's stature is an important clinical factor to
      consider when assessing hospitalized patients with ischemic stroke. We determined
      the relation of body height with clinical characteristics and discharge outcomes
      among persons with ischemic stroke. METHODS: we analyzed prospectively collected
      data in 881 consecutive patients with ischemic stroke admitted to a university
      hospital stroke service during a 5-year period starting September 2002. Stroke
      subtyping was performed per modified Trial of ORG 10172 in Acute Stroke Treatment
      (TOAST) criteria. Stroke severity was assessed with the National Institutes of
      Health Stroke Scale. All patients were assessed at discharge using the modified
      Rankin scale. Mean adjusted height was compared using linear regression models
      with height as outcome, and stroke subtype, modified Rankin scale, and potential
      confounders as covariates. RESULTS: mean age was 67.4 years, 48% were women. Mean
      height was 169 cm (SD +/- 11). In multivariable analysis, height decreased per
      year of age (P=0.003), those with a previous stroke were shorter than those
      without a previous stroke (P=0.04), and females were shorter than males
      (P<0.001). Height was not associated with stroke subtype or discharge outcomes in
      unadjusted or adjusted analyses. CONCLUSIONS: Body height at hospital admission
      has no relation to ischemic stroke subtype or discharge outcome. However,
      patients with history of previous stroke were significantly shorter than those
      without a previous stroke, which may be because of greater stroke occurrence in
      shorter individuals or taller people with relatively larger atrial fibrillation
      related strokes dying earlier.

PMID- 21192189
TI  - Case of singing seizure using syllable names.
AB  - We report a case of a patient with singing seizures, who was able to sing
      familiar songs by syllable name with no earlier practice. The patient was a 56
      year-old musically naive woman who developed singing seizures when she was in her
      early 20s. She suddenly began singing familiar sacred songs by syllable name,
      even though she had never practiced the songs using a musical score or had
      earlier sung them by syllable name. An electroencephalogram showed bilateral low
      voltage spikes that were significantly pronounced in the right temporal lobe.
      Technetium-99m-bicisate ethyl cysteinate dimer single photon emission computed
      tomography also showed hypoperfusion in the medial right temporal lobe. The right
      temporal lobe may be involved in singing, and there may be an automatic and
      unconscious analytical system of music perception that arranges each tone into
      its syllable name.

PMID- 21192190
TI  - Focal status epilepticus induced by hyperbaric oxygen therapy.
AB  - INTRODUCTION: generalized tonic clonic (GTC) seizure activity because of central
      nerve system oxygen toxicity is a rare but recognized effect of HBOT (hyperbaric
      oxygen therapy). Almost all case reports and database analyses about the
      relationship between seizure activity and HBOT point out that GTC seizures and
      status epilepticus are more likely to occur as a result of the treatment and
      there are only few reports demonstrating partial seizures. CASE REPORT: an 87
      year-old male patient was admitted to our clinic because of tonic-clonic
      contractions on his left arm. He was under HBOT because of a decubitis ulcer.
      After repeated exposures to hyperbaric oxygen, he had contractions on his left
      arm. He was diagnosed as focal motor status. There was no evidence of acute
      ischemia or mass lesion on brain magnetic resonance imaging. IV phenytoin
      (diphenylhydantoin) 20 mg/kg was given over 30 minutes and continued orally with
      phenytoin at a dose of 300 mg/d. He had no subsequent seizures. CONCLUSION: GTC
      seizures or status epilepticus as a result of GTC seizures are more common than
      focal seizures as neurologic complications of HBOT. Partial seizures as a
      neurologic complication of HBOT have rarely been reported and to our knowledge,
      this is the first case which is characterized by focal status epilepticus induced
      by HBOT.

PMID- 21192191
TI  - Multiple cerebral infarction and cardiomyopathy with pheochromocytoma.
AB  - A 44-year-old woman was admitted to our hospital with altered mental status and
      weakness in the left upper and lower limbs. A brain magnetic resonance imaging
      indicated multiple cerebral infarctions in the bilateral frontal and parietal
      lobes and in the left occipital lobe. Magnetic resonance angiography indicated
      overall arterial wall irregularity and stenosis. An electrocardiogram showed
      negative T waves, troponin I was elevated at 0.60 ng/mL, and an echocardiogram
      showed severe hypokinesis, leading to a diagnosis of ischemic heart disease;
      however, no stenosis was found at cardiac catheterization. No other etiology for
      the angiopathy could be found. Whole-body computed tomography demonstrated an
      adrenal tumor and urinary catecholamine levels were elevated. Following excision
      of the adrenal tumor, a diagnosis of pheochromocytoma was made. Postoperatively,
      the patient's arterial stenosis and cardiac abnormalities improved. It was
      hypothesized that the patient's cardiomyopathy and vasospasm were secondary to
      excessive catecholamine secretion from the pheochromocytoma.

PMID- 21192192
TI  - Becker myotonia congenita associated with Wolff-Parkinson-White syndrome.
AB  - Becker's disease is a congenital myotonia with an autosomal recessive pattern of
      inheritance. Unlike myotonic dystrophy, it is not associated with cardiopathy. We
      present a 32-year-old man with Becker's disease diagnosed at age 11. He suffered
      episodes of loss of consciousness preceded by palpitations when he performed
      strenuous physical exercise. The electrocardiogram reveals a Wolff-Parkinson
      White syndrome. Review of the literature in MEDLINE using the search terms of
      congenital myotonia or Becker's disease and arrhythmia or heart disease only
      found 2 articles on Thomsen disease but none on Becker's disease. Becker's
      myotonia congenita may exceptionally be associated with cardiopathy, thus
      patients with this disorder should have a cardiac evaluation.

PMID- 21192193
TI  - Xylometazoline abuse induced ischemic stroke in a young adult.
AB  - INTRODUCTION: substance abuse is an important cause of ischemic stroke in the
      young. This includes over-the-counter dietary supplements and cough and cold
      remedies, which were reported to be an independent risk factor for hemorrhagic
      stroke. CASE REPORT: this article describes a young male patient with acute
      ischemic infarctions in the posterior inferior cerebellar and posterior cerebral
      artery territories bilaterally, the right cerebral peduncle, the left pontine
      tegmentum, and lateral pons following abuse of xylometazoline-containing nasal
      decongestant for 10 years. CONCLUSION: this is the first report in the literature
      of posterior circulation strokes because of chronic xylometazoline abuse. We hope
      to contribute to increase knowledge and awareness of the public about these
      serious complications of cough-and-cold remedies as well as dietary supplements
      containing sympathomimetics.

PMID- 21192194
TI  - Wallenberg's syndrome with proximal quadriparesis.
AB  - BACKGROUND: there are several variants of Wallenberg's syndrome. Wallenberg's
      syndrome with proximal quadriparesis has not been reported before. CASE SUMMARY:
      we report a 25-year-old woman presenting with sudden onset of vertigo,
      hoarseness, dysphagia, right facial numbness, and proximal quadriparesis. Brain
      magnetic resonance imaging revealed right posterolateral medullary infarction
      with medial extension and sparing of the pyramidal tracts. The proximal
      quadriparesis improved substantially 2 weeks after stroke onset. CONCLUSION: the
      proximal quadriparesis can be explained by involvement of the right medial
      medullary reticular formation. Our observation supports the hypothesis that the
      proximal part of the limb is bilaterally innervated by axons of the
      corticoreticulospinal tracts in human beings. The rapid recovery of proximal
      quadriparesis also supports the concept that a functional pyramidal tract seems
      crucial for recovery after stroke.

PMID- 21192195
TI  - Spinal cord infarction in a woman with cardiac fibroelastoma.
AB  - A 61-year-old woman presented with the acute onset of right lower extremity
      paresthesias followed within 15 minutes by complete bilateral lower extremity
      paralysis and urinary incontinence. Magnetic resonance imaging of the thoracic
      spine, using a 1.5 Tesla magnetic resonance scanner with echo planar imaging
      technique, showed an intramedullary T2 hyperintense lesion that involved the
      central gray matter and portions of the white matter, extending from the T8 level
      to the conus medullaris. Diffusion weighted imaging of the spine showed
      restricted diffusion in an area corresponding to that of the T2 lesion. A
      transesophageal echocardiogram demonstrated a highly mobile oscillating mass
      attached to the left leaflet of the aortic valve, consistent with fibroelastoma.
      Fibroelastoma is an uncommon benign cardiac tumor that has been associated with
      cerebral embolic complications. It is our belief that this tumor and spinal cord
      infarction is exceedingly rare and only one such occurrence has been previously
      reported.

PMID- 21192196
TI  - Toxoplasmosis myelopathy and myopathy in an AIDS patient: a case of immune
      reconstitution inflammatory syndrome?
AB  - INTRODUCTION: concurrent toxoplasmosis infection of the brain, spinal cord, and
      muscle has never been reported together in a patient antemortem. Toxoplasma
      gondii is the most common focal central nervous system opportunistic infection in
      the acquired immune deficiency syndrome (AIDS) population. Despite this fact,
      isolated toxoplasmosis infection in the spinal cord is rarely reported. In
      addition, toxoplasmic myositis is also rarely diagnosed and Toxoplasma cysts are
      seldom found on biopsy. We present a patient with AIDS and toxoplasmosis
      resistant to standard anti-Toxoplasma therapy. CASE REPORT: a 34-year-old man
      with a history of untreated AIDS presented with symptoms of myelopathy.
      Pathologically proven toxoplasmosis of the spinal cord was diagnosed and no brain
      lesions were found. However, despite appropriate treatment and initiation of
      highly active antiretroviral therapy, the patient developed worsening symptoms,
      including myopathy and autonomic instability. Muscle biopsy revealed Toxoplasma
      cysts, and there was laboratory evidence of a restored immune system. CONCLUSION:
      we report the first case of toxoplasmosis presenting initially with myelitis in
      the absence of encephalitis that subsequently progressed to myositis despite
      antiparasitic treatment. We also discuss the possibility of immune reconstitution
      inflammatory syndrome as a cause of his deterioration.

PMID- 21192197
TI  - Chordoid glioma: a case report and literature review.
AB  - BACKGROUND: chordoid glioma is a rare tumor (World Health Organization grade II)
      with both glial and chordoid features, often located in the suprasellar region
      and anterior third ventricle. It was first described by Brat in 1998. Because
      there is no detailed information available from the clinical perspective, we
      reviewed the literature. METHODS: a literature search through PUBMED and CNKI
      revealed 64 cases of chordoid glioma. Information on the clinical course was very
      limited. We reviewed the literature and studied the pathologic and imaging
      features, postoperative mortality and morbidity in relation to surgical extension
      and approaches, and the importance of adjuvant treatment. CONCLUSIONS: mortality
      in the immediate postoperative period is 28%, and postoperative morbidity is 60%,
      which are statistically higher after gross total resection as compared with
      subtotal resection. Translamina terminalis approach is considered to be the best
      approach. The current study cannot document that patients have longer survival
      and higher quality of life after gross total resection than subtotal resection.
      The role of postoperative radiotherapy is uncertain and there is no report on the
      use of chemotherapy. More information about the optimal treatment strategy is
      needed.

PMID- 21192198
TI  - 10 commonly asked questions about Parkinson disease.

PMID- 21192199
TI  - Surgical decompression improves mortality and morbidity after large territory
      acute cerebral infarction: a critically appraised topic.
AB  - BACKGROUND: patients who suffer from large territory cerebral infarctions have
      poor prognosis. Whether adjunctive surgical therapy improves clinical outcomes
      has long been a controversial topic. OBJECTIVE: to determine whether surgical
      decompression, compared with best medical management, improves mortality and
      morbidity in the setting of a large territory acute middle cerebral artery
      infarction. METHODS: the objective was addressed through the development of a
      structured critically appraised topic. This included development of a clinical
      scenario, structured clinical questions, search strategy and selection of an
      article, critical appraisal, evidence summary, clinical bottom lines, and expert
      commentary from vascular neurologists and a vascular neurosurgeon. RESULTS: the
      study selected for appraisal included data from both a multicenter randomized
      trial and an updated meta-analysis. Surgical decompression within 4 days of
      stroke onset did not reduce the risk of poor outcome [absolute risk reduction
      (ARR), 0%; 95% confidence interval (CI), -21% to 21%]; however, it did reduce
      case fatality (ARR, 38%; 95% CI, 15% to 60%). The updated meta-analysis showed
      that surgical decompression within 48 hours of stroke onset reduces both poor
      outcome [ARR, 42%; 95% CI, 23% to 56%; number needed to treat (NNT)=2; 95% CI, 2
      to 4] and case fatality (ARR, 50%; 95% CI, 32% to 64%; NNT=2; 95% CI, 2 to 3).
      CONCLUSIONS: early surgical decompression (within 48 h of stroke onset) reduces
      the risks of death and poor clinical outcome at 1 year in patients with large
      territory cerebral infarction.

PMID- 21192200
TI  - Designing a management system.

PMID- 21192201
TI  - Assessing the evidence of Six Sigma and Lean in the health care industry.

PMID- 21192202
TI  - Using rapid cycle improvement methods in resource-limited settings.

PMID- 21192203
TI  - A healthcare Lean Six Sigma System for postanesthesia care unit workflow
      improvement.
AB  - BACKGROUND: The aim of this article is to propose a new model called Healthcare
      Lean Six Sigma System that integrates Lean and Six Sigma methodologies to improve
      workflow in a postanesthesia care unit. METHODS: The methodology of the proposed
      model is fully described. A postanesthesia care unit case study is also used to
      demonstrate the benefits of using the Healthcare Lean Six Sigma System model by
      combining Lean and Six Sigma methodologies together. RESULTS: The new model
      bridges the service gaps between health care providers and patients, balances the
      requirements of health care managers, and delivers health care services to
      patients by taking the benefits of the Lean speed and Six Sigma high-quality
      principles. CONCLUSIONS: The full benefits of the new model will be realized when
      applied at both strategic and operational levels. For further research, we will
      examine how the proposed model is used in different real-world case studies.

PMID- 21192204
TI  - Managing health care decisions and improvement through simulation modeling.
AB  - Simulation modeling is a way to test changes in a computerized environment to
      give ideas for improvements before implementation. This article reviews research
      literature on simulation modeling as support for health care decision making. The
      aim is to investigate the experience and potential value of such decision support
      and quality of articles retrieved. A literature search was conducted, and the
      selection criteria yielded 59 articles derived from diverse applications and
      methods. Most met the stated research-quality criteria. This review identified
      how simulation can facilitate decision making and that it may induce learning.
      Furthermore, simulation offers immediate feedback about proposed changes, allows
      analysis of scenarios, and promotes communication on building a shared system
      view and understanding of how a complex system works. However, only 14 of the 59
      articles reported on implementation experiences, including how decision making
      was supported. On the basis of these articles, we proposed steps essential for
      the success of simulation projects, not just in the computer, but also in
      clinical reality. We also presented a novel concept combining simulation modeling
      with the established plan-do-study-act cycle for improvement. Future scientific
      inquiries concerning implementation, impact, and the value for health care
      management are needed to realize the full potential of simulation modeling.

PMID- 21192205
TI  - A standardized pain management protocol improves timeliness of analgesia among
      emergency department patients with renal colic.
AB  - BACKGROUND: Kidney stones are a common, and extremely painful, cause of emergency
      department (ED) visits. Pain management is a critical component of high-quality
      patient care. A pilot study at our institution found that only 69% of ED patients
      with renal colic had evidence of clinically significant analgesia. OBJECTIVE: In
      response to these findings, we evaluated the impact of a formalized pain
      management protocol on timeliness of analgesia among ED patients with renal
      colic. SUBJECTS AND METHODS: Using a before and after study design, adult ED
      patients with renal colic were eligible. In the prospective arm, patients were
      treated with ketorolac, 30 mg intravenous, and morphine, 0.05-0.1 mg/kg
      intravenous, according to a standardized protocol. Results were compared with a
      retrospective chart review of eligible patients treated during a similar
      preprotocol period. RESULTS: Implementation of the protocol resulted in a
      significant reduction in time to effective analgesia (72 +/- 63 vs 37 +/- 42
      minutes, P = .003). The protocol did not result in any increase in adverse
      effects. CONCLUSION: Implementation of a standardized pain management protocol
      among ED patients with renal colic resulted in a marked improvement in quality of
      care as evidenced by a 49% reduction in time to effective analgesia.

PMID- 21192206
TI  - Appreciative Inquiry for quality improvement in primary care practices.
AB  - PURPOSE: To test the effect of an Appreciative Inquiry (AI) quality improvement
      strategy on clinical quality management and practice development outcomes.
      Appreciative inquiry enables the discovery of shared motivations, envisioning a
      transformed future, and learning around the implementation of a change process.
      METHODS: Thirty diverse primary care practices were randomly assigned to receive
      an AI-based intervention focused on a practice-chosen topic and on improving
      preventive service delivery (PSD) rates. Medical-record review assessed change in
      PSD rates. Ethnographic field notes and observational checklist analysis used
      editing and immersion/crystallization methods to identify factors affecting
      intervention implementation and practice development outcomes. RESULTS: The PSD
      rates did not change. Field note analysis suggested that the intervention
      elicited core motivations, facilitated development of a shared vision, defined
      change objectives, and fostered respectful interactions. Practices most likely to
      implement the intervention or develop new practice capacities exhibited 1 or more
      of the following: support from key leader(s), a sense of urgency for change, a
      mission focused on serving patients, health care system and practice flexibility,
      and a history of constructive practice change. CONCLUSIONS: An AI approach and
      enabling practice conditions can lead to intervention implementation and practice
      development by connecting individual and practice strengths and motivations to
      the change objective.

PMID- 21192207
TI  - Up close and (inter)personal: insights from a primary care practice's efforts to
      improve office relationships over time, 2003-2009.
AB  - A growing body of literature suggests that interpersonal relationships between
      personnel in health care organizations can have an impact on the quality of care
      provided. Some research recommends that the fundamental practice transformation
      that is being urged in this current climate of health care reform may be aided by
      strong interpersonal practice relationships and communication. There is much to
      be learned, however, about what is involved in the process of addressing and
      improving interpersonal relationships in primary care practices. This case study
      offers insights into this process by examining 1 primary care practice's efforts
      to address interpersonal office issues over the course of its participation in 2
      back-to-back quality improvement (QI) intervention studies. Our analysis is based
      on extensive qualitative data on this practice (observational data, interviews,
      and audio-recorded QI meetings) from 2003 to 2009. By tracing common themes and
      patterns of interaction over an extended period of time, we identify a variety of
      facilitators of and barriers to addressing interpersonal issues in the practice
      setting. We conclude by suggesting some implications from this case for future QI
      research.

PMID- 21192208
TI  - No payment for preventable complications: reviewing the early literature for
      content, guidance, and impressions.
AB  - In 2008, the Centers for Medicare & Medicaid Services (CMS) implemented a policy
      of not paying hospitals for the care of several preventable hospital-acquired
      conditions. The CMS policy is a unique value-based purchasing initiative because
      it relies on penalties rather than on rewards. Because of its novelty, less is
      known in advance about how this type of payment approach might work, get
      implemented, or be viewed by stakeholders in health care. As a result, the early
      published literature focusing on the CMS policy may serve as an important frame
      of reference among managers, policy makers, and researchers for guiding attitudes
      and behaviors. This review examines over an initial 3-year period academic and
      trade articles addressing the CMS policy to gain the impressions, guidance, and
      content provided in this literature. Key findings include an inordinately small
      number of articles focused on the new CMS policy; little original research or
      empirical prediction on CMS policy implementation and outcomes; a highly
      opinionated, non-evidence-based literature; a literature less able to address the
      policy impact for specific preventable complications or hospital settings; and a
      high percentage of articles making inconsistent, broad-based linkages between the
      CMS policy and specific quality improvement initiatives that potentially limit
      the policy's long-term acceptance as an improvement strategy.

PMID- 21192212
TI  - Using in situ simulation to identify and resolve latent environmental threats to
      patient safety: case study involving a labor and delivery ward: retraction.

PMID- 21192209
TI  - International medical travelers, length of stay, and the continuum of care:
      inquiry and comparison.
AB  - PURPOSE: In this study, we assess whether length of stay (LOS) is associated with
      patient geographic origin and whether payment source for international patients
      explains differences in LOS. METHODS: We used a retrospective case-control study
      to compare inbound international patients coming to the United States and
      domestic patients, who were admitted to academic medical centers (AMCs) between
      October 2005 and September 2008. International patients were matched to domestic
      patients on the basis of age, gender, AMC, admission status, severity of illness
      (SOI), and Medicare Severity Diagnosis-Related Group. RESULTS: International
      patients stayed significantly longer than domestic patients, with an average LOS
      of 6.9 days (SD = 14.0) compared with 6.0 days (SD = 5.3) for domestic patients
      (P < .001). There was no difference in LOS between patients with international
      commercial and international self-pay payment sources (P = .108). Results of the
      multivariate analysis showed that international patients with extreme SOI stayed
      21% longer than otherwise similar domestic patients with extreme SOI (P = .012).
      CONCLUSIONS: The most complex international patients coming to US AMCs have
      substantially longer LOS than the most complex domestic patients, even after
      controlling for demographic characteristics, and type of condition. More research
      is needed to understand the underlying drivers of these differences.

PMID- 21192213
TI  - Biomechanical comparison of transpedicular versus intralaminar C2 fixation in C2
      C6 subaxial constructs.
AB  - STUDY DESIGN: Biomechanical study. OBJECTIVE: To compare the relative rigidity of
      C2 transpedicular versus intralaminar fixation with and without offset connectors
      in C2-C6 subaxial constructs. SUMMARY OF BACKGROUND DATA: Insufficient
      biomechanical data exists on C2 laminar fixation in subaxial constructs, and no
      study has considered C2-C6 subaxial constructs or the use of offset connectors.
      METHODS: Six fresh-frozen cadaveric cervical spines underwent rigidity testing in
      the intact condition and after a destabilizing C3-C6 laminectomy. Specimens were
      instrumented with 20 mm pedicle and 20 mm intralaminar screws at C2, and with 14
      mm lateral mass screws from C3-C6. In random order, three conditions (C2 pedicle
      screws, C2 laminar screws, and C2 laminar screws with offset connectors) were
      tested in flexion-extension, axial rotation, and lateral bending. RESULTS:
      Laminar screws in C2-C6 constructs were equivalent to transpedicular fixation in
      flexion-extension (P = 0.985), were significantly more rigid than pedicle screws
      in axial rotation (P = 0.002), and were significantly less rigid than pedicle
      screws in lateral bending (P = 0.002). Laminar screw constructs were more rigid
      than the intact condition in all planes.

PMID- 21192214
TI  - Changes in lumbar movement in people with low back pain are related to
      compromised balance.
AB  - STUDY DESIGN: Comparing people with and without low back pain (LBP). OBJECTIVES:
      This study aimed to investigate lumbar spine movement and the quality of postural
      recovery in response to unexpected postural perturbation in people with LBP.
      SUMMARY OF BACKGROUND DATA: People with chronic LBP tend to use lumbar spine
      motion less frequently for postural control than pain-free individuals, and after
      voluntary arm movement, they need more time and a greater number of postural
      adjustments to regain postural equilibrium. We hypothesize that motion of the
      lumbar spine is altered in people with chronic LBP, and this would be associated
      with compromised control of postural stability in response to unexpected
      perturbation. METHODS: The response to a sudden load imposed by a weight dropped
      into a box held in the hands was studied in 11 individuals with chronic LBP and
      matched controls. Lumbopelvic motion was recorded with an electromagnetic motion
      analysis system. Time to recover balance was calculated from ground reaction
      forces. RESULTS: People with LBP had a delayed initiation of lumbar spine flexion
      (angular displacement) (Control = 44.9 [25.1] ms, LBP = 90.2 [42.3] ms, P <
      0.001) and took longer to regain postural stability (Control = 460.4 [123.4] ms,
      LBP = 761.0 [194.2] ms, P < 0.001) after the perturbation. CONCLUSION: These data
      provide further evidence that the quality of balance control is compromised in
      LBP patients and that this is associated with poor use of spinal motion as a
      component of the postural strategy.

PMID- 21192215
TI  - Male-female differences in Scoliosis Research Society-30 scores in adolescent
      idiopathic scoliosis.
AB  - STUDY DESIGN: Longitudinal cohort study. OBJECTIVE: To compare functional
      outcomes between male and female patients before and after surgery for adolescent
      idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: There is no clear
      consensus in the existing literature with respect to sex differences in
      functional outcomes in the surgical treatment of AIS. METHODS: A prospective,
      consecutive, multicenter database of patients who underwent surgical correction
      for adolescent idiopathic scoliosis was analyzed retrospectively. All patients
      completed Scoliosis Research Society-30 (SRS-30) questionnaires before and 2
      years after surgery. Patients with previous spine surgery were excluded. Data
      were collected for sex, age, Risser grade, previous bracing history, maximum
      preoperative Cobb angle, curve correction at 2 years, and SRS-30 domain scores.
      Paired sample t tests were used to compare preoperative and postoperative scores
      within each sex. Independent sample t tests were used to compare scores between
      sexes. A P value of <0.05 was considered statistically significant. RESULTS:
      Seven hundred forty-four patients (621 females and 123 males) were included. On
      average, males were 1 year older than females. There were no differences between
      sexes in Risser grade, bracing history, maximum curve magnitude, or correction
      after surgery. Both males and females had similar improvement in all SRS-30
      domains after surgery. Self-image/appearance had the greatest relative
      improvement. Males had better self-image/appearance scores preoperatively, better
      pain scores at 2 years, and better mental health and total scores both
      preoperatively and at 2 years. Both males and females were similarly satisfied
      with surgery. CONCLUSIONS: Males treated with surgery for AIS report better
      preoperative self-image, less postoperative pain, and better mental health than
      females. These differences may be clinically significant. For both males and
      females, the most beneficial effect of surgery is improved self-image/appearance.
      Overall, the benefits of surgery for AIS are similar for both sexes.

PMID- 21192216
TI  - Incidence, risk factors and classification of proximal junctional kyphosis:
      surgical outcomes review of adult idiopathic scoliosis.
AB  - STUDY DESIGN: Retrospective case series of surgically treated adult scoliosis
      patients. OBJECTIVE: To assess the incidence, risk factors and clinical outcomes
      of proximal junctional kyphosis (PJK) in a large series of adult idiopathic
      scoliosis patients undergoing long instrumented spinal fusion (.5 vertebrae). A
      new classification is also projected. SUMMARY OF BACKGROUND DATA: Maintaining
      both coronal and sagittal balance is essential in the surgical treatment of adult
      deformity patients. PJK is a well-recognized postoperative phenomenon in adults
      and adolescents after scoliosis surgery. Despite recent reports, the prevalence,
      clinical outcomes, and the risk factors of PJK are still controversial. MATERIALS
      AND METHODS: This study is a retrospective review of the charts and radiographs
      of 157 consecutive patients with adult scoliosis treated with long instrumented
      spinal fusion. PJK was defined by a proximal junctional angle greater than 108
      and at least 108 greater than the corresponding preoperative measurement.
      Radiographic measurements included sagittal vertical axis (SVA), thoracic
      kyphosis (TK), lumbar lordosis (LL) and pelvic incidence (PI) on preoperative,
      immediate postoperative and at follow-up. Bone mineral density (BMD), Body mass
      index (BMI), age, sex, instrumentation type, surgery type, and fusion to sacrum
      were reviewed. Postoperative SRS outcome scores and Oswestry Disability Index
      (ODI) were also evaluated. PJK was graded by the severity and type. Means were
      compared with Student's t test and chi2 test. P value of less than 0.05 with
      confidence interval 95% was considered significant. RESULTS: The average age was
      46.9 years (22-81 years) and the average Follow-up was 4.3 years (2-12 years).
      PJK occurred in 32 patients (20%) and were mostly classified as 1A (Ligamentous &
      mild) deformity. The SRS outcome scores and ODI did not demonstrate significant
      differences between PJK group and non-PJK group, four patients had additional
      surgeries performed for local pain. Fusion to the sacrum and posterior fusion
      with segmental instrumentation were significant risk for PJK (P = 0.03, P <
      0.01). BMD, BMI, age, sex, and instrumentation type showed no difference. Eighty
      four percent of PJK group was associated with TK 1 LL 1 PI .458 or preoperation
      to postoperation SVA more than 50 mm vs. 6.4% of non-PJK group (P < 0.01, P <
      0.01). CONCLUSION: Despite the occurrence of PJK in 20% of adult scoliosis
      patients undergoing long fusion, no significant differences were found in SRS
      outcome scores and ODI in PJK and non-PJK patients. Fusion to the sacrum and
      posterior fusion with segmental instrumentation were identified as risk factors.
      PJK can be minimized by post-operative normalization of global sagittal
      alignment. A simplified classification based in severity type of PJK showed the
      majority in class 1A (ligamentous lesion and mild deformity).

PMID- 21192217
TI  - Juvenile xanthogranuloma in an adult lumbar spine: a case report.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To report a very rare case of juvenile
      xanthogranuloma (JXG) of the spine in an adult. SUMMARY OF BACKGROUND DATA: JXG
      is very rare in the spine, with only five prior reports in infants and children.
      To the best of our knowledge, this tumor has never been reported in an adult
      spine. METHODS: The patient is a 47-year-old woman who presented with bowel and
      bladder incontinence. Magnetic resonance imaging showed a very large lesion
      arising from the L2 vertebral body, with massive extension into the
      retroperitoneum with extensive intradural involvement. She had decreased rectal
      tone, had 4/5 strength in the right hip flexor, and had diminished sensation in
      her anterior right thigh and perineal region. She was otherwise neurologically
      intact. After preoperative embolization, a decompressive laminectomy was
      performed and the tumor was resected through a posterolateral transpedicular
      approach, followed by stabilization. Because of extensive involvement of
      retroperitoneum, complete resection was not possible. RESULTS: After pathologic
      evaluation of the specimen, a diagnosis of JXG was made. Patient underwent
      postoperative radiation therapy, and her neurologic examination improved
      significantly over the next several months. CONCLUSIONS: To the best of our
      knowledge, this is the first reported case of JXG in an adult spine. Although
      complete resection of the tumor was not possible, decompression of the dural sac
      followed by postoperative radiation led to an excellent clinical outcome.

PMID- 21192218
TI  - Health and health care are verbs: health care delivery science: the new science.

PMID- 21192219
TI  - Plate-only open door laminoplasty maintains stable spinal canal expansion with
      high rates of hinge union and no plate failures.
AB  - STUDY DESIGN: Prospective clinical series. OBJECTIVE: To evaluate the ability of
      plate-only laminoplasty to achieve stable laminar arch reconstruction and to
      determine the rate and time course with which bony healing occurs in such
      constructs. SUMMARY OF BACKGROUND DATA: Reconstruction of a stable laminar arch
      with sufficient room for the decompressed spinal cord is a desired goal when
      performing cervical laminoplasty for myelopathy. Traditional forms of
      laminoplasty fixation, such as sutures, bone struts, and ceramic spacers, may be
      associated with complications including loss of fixation, dislodgement with
      neurologic compromise, and premature laminoplasty closure. Plates, in contrast,
      provide more rigid fixation. Plate-only laminoplasty is gaining popularity as a
      method of laminoplasty fixation, but there is little data on its effectiveness.
      METHODS: Fifty-four patients who underwent open door laminoplasty for cervical
      myelopathy and had available postoperative computed tomography (CT) scans formed
      the basis of this study. In all cases, a 4-mm round burr was used to create the
      hinge at the junction of the lateral mass and lamina by completely removing the
      dorsal cortex and thinning the ventral cortex until a greenstick deformation of
      the hinge could be produced. Laminoplasty plates were used as the sole method of
      fixation. No supplemental bone graft struts were used on the plated side, and the
      hinge side was not bone grafted. Axial CT scans obtained at 3, 6, and 12 months
      postoperatively were assessed for plate complications and bony healing of the
      hinge. RESULTS: No plate failures, dislodgements, or premature closures occurred
      in any of the levels at any time postoperatively. Computed tomography scan review
      demonstrated that 55% of levels were healed at 3 months, 77% at 6 months, and 93%
      at 12 months. At each timepoint, C6 and C7 had the highest hinge healing rates.
      Laminar screw backout was seen in 5/217 (2.3%) of levels, but was not associated
      with plate dislodgement, laminoplasty closure, or neurologic consequences, and
      did not occur in any case in which 2 laminar screws had been placed. CONCLUSION:
      Plate-only laminoplasty provided stable reconstruction of an expanded laminar
      arch with no failures, dislodgements, adverse neurologic consequences, or
      premature closures in 217 levels. Ninety-three percent of hinges demonstrated
      radiographic union at 12 months, and even those that did not heal by CT scan
      criteria maintained patent expansion of the spinal canal without adverse
      neurologic consequences. Supplemental bone graft does not appear necessary when
      plated laminoplasty is performed.

PMID- 21192220
TI  - Neurologic improvement after thoracic, thoracolumbar, and lumbar spinal cord
      (conus medullaris) injuries.
AB  - STUDY DESIGN: Retrospective. OBJECTIVE: With approximately 10,000 new spinal cord
      injury (SCI) patients in the United States each year, predicting public health
      outcomes is an important public health concern. Combining all regions of the
      spine in SCI trials may be misleading if the lumbar and sacral regions (conus)
      have a neurologic improvement at different rates than the thoracic or
      thoracolumbar spinal cord. SUMMARY OF BACKGROUND DATA: Over a 10-year period
      between January 1995 to 2005, 1746 consecutive spinal injured patients were seen,
      evaluated, and treated through a level 1 trauma referral center. A retrospective
      analysis was performed on 150 patients meeting the criteria of T4 to S5 injury,
      excluding gunshot wounds. One-year follow-up data were available on 95 of these
      patients. METHODS: Contingency table analyses (chi-squared statistics) and
      multivariate logistic regression. Variables of interest included level of injury,
      initial American Spinal Injury Association (ASIA), age, race, and etiology.
      RESULTS: A total of 92.9% of lumbar (conus) patients neurologically improved one
      ASIA level or more compared with 22.4% of thoracic or thoracolumbar spinal cord
      injured patients. Only 7.7% of ASIA A patients showed neurologic improvement,
      compared with 95.2% of ASIA D patients; ASIA B patients demonstrated a 66.7%
      improvement rate, whereas ASIA C had a 84.6% improvement rate. When the two
      effects were considered jointly in a multivariate analysis, ASIA A and
      thoracic/thoracolumbar patients had only a 4.1% rate of improvement, compared
      with 96% for lumbar (conus) and incomplete patients (ASIA B-D) and 66.7% to 72.2%
      for the rest of the patients. All of these relationships were significant to P <
      0.001 (chi-square test). There was no link to age or gender, and race and
      etiology were secondary to region and severity of injury. CONCLUSION: Thoracic
      (T4-T9) SCIs have the least potential for neurologic improvement. Thoracolumbar
      (T10-T12) and lumbar (conus) spinal cord have a greater neurologic improvement
      rate, which might be related to a greater proportion of lower motor neurons.
      Thus, defining the exact region of injury and potential for neurologic
      improvement should be considered in future clinical trial design. Combining all
      anatomic regions of the spine in SCI trials may be misleading if different
      regions have neurologic improvement at different rates. Over a ten-year period,
      95 complete thoracic/thoracolumbar SCI patients had only a 4.1% rate of
      neurologic improvement, compared with 96.0% for incomplete lumbar (conus)
      patients and 66.7% to 72.2% for all others.

PMID- 21192221
TI  - Intraoperative and early postoperative complications in extreme lateral interbody
      fusion: an analysis of 600 cases.
AB  - STUDY DESIGN: Prospective analysis of 600 extreme lateral interbody fusion (XLIF)
      approach procedures for intraoperative and perioperative complications.
      OBJECTIVE: To delineate and describe complications in a large, prospective series
      of minimally invasive lateral lumbar fusion procedures (XLIF). SUMMARY OF
      BACKGROUND DATA: While some small series of lateral lumbar fusion have discussed
      complications, no results from large studies have been reported. METHODS: A total
      of 600 patients were treated with a lateral approach to fusion (XLIF) for
      degenerative spinal conditions. Data were collected prospectively on all patients
      and analyzed for demographic, diagnostic, and hospitalization information to
      identify operative and early postoperative complications. Documented complication
      types and rates in this large series were compared with smaller prior reports on
      lateral approach fusions, as well as other minimally invasive (mini-anterior
      lumbar interbody fusion and minimally invasive surgical [MIS] transforaminal
      lumbar interbody fusion) and more traditional fusion approaches (posterior
      intertransverse fusion, anterior lumbar interbody fusion, posterior lumbar
      interbody fusion, transforaminal lumbar interbody fusion). RESULTS: Seven hundred
      forty-one levels were treated, 80.8% single level, 15.0% 2 level, 4.0% 3 level,
      0.2% 4 level; 59.3%, including the L4 to L5 levels. A total of 99.2% included
      supplemental internal fixation; 83.2% included pedicle screw fixation
      (predominantly unilateral). Hemoglobin change from pre- to postoperation averaged
      1.38. Hospital stay averaged 1.21 days. The overall incidence of perioperative
      complications (intraoperation and out to 6 weeks postoperation) was 6.2%: 9
      (1.5%) in-hospital surgery-related events, 17 (2.8%) in-hospital medical events,
      6 (1.0%) out-of-hospital surgery-related events, and 5 (0.8%) out-of-hospital
      medical events. There were no wound infections, no vascular injuries, no
      intraoperative visceral injuries, and 4 (0.7%) transient postoperative neurologic
      deficits. Eleven events (1.8%) resulted in additional procedures/reoperation.
      CONCLUSIONS: Compared with traditional open approaches, the MIS lateral approach
      to fusion by using the XLIF technique resulted in a lower incidence of infection,
      visceral and neurologic injury, and transfusion as well as markedly shorter
      hospitalization. Complications in MIS XLIF compare favorably with those from
      other MIS fusion procedures; duration of hospitalization is shorter than with any
      previously reported technique.

PMID- 21192222
TI  - Genetic variants in melatonin synthesis and signaling pathway are not associated
      with adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: Genetic association study investigating the association of genetic
      markers of melatonin signaling and biosynthesis with adolescent idiopathic
      scoliosis (AIS). OBJECTIVE: To determine whether gene polymorphisms related to
      the melatonin signaling or biosynthesis pathways are associated with AIS. SUMMARY
      OF BACKGROUND DATA: Data have been published on the potential role of gene
      polymorphisms for melatonin receptor (MTNR) 1B in predicting AIS. Other genes in
      the melatonin pathways have been tested for association with AIS. METHODS: The
      following genes involved in melatonin synthesis were evaluated herein: tryptophan
      5-hyroxylase 1 (TPH1), serotonin N-acetyltransferase (SNAT), and hydroxyindoleo
      methyltransferase (HIOMT). In addition, proteins involved in melatonin signaling
      were also included in this study: MTNR1A, MTNR1B, and protein kinase C delta
      (PKCd). High throughput microarray-based single nucleotide polymorphism (SNP)
      genotyping was performed for these seven genes using DNA samples from 589 AIS
      subjects and 1533 ethnically matched controls. Chi-square analyses of allele
      frequency between AIS cases and controls were performed and odds ratios were
      calculated for all SNP markers. RESULTS: Three SNPs were tested for both MTNR1A
      and HIOMT, 4 for TPH1 and SNAT, 12 for PKCd, and 7 for MTNR1B. The minor allele
      frequencies were not significantly different between AIS cases and controls. No
      association was thus found between AIS and the investigated SNPs. CONCLUSIONS:
      Genetic polymorphisms associated with either melatonin synthesis or its signaling
      pathway are unlikely to be commonly associated with AIS.

PMID- 21192225
TI  - Risk of vertebrobasilar stroke and chiropractic care: results of a population
      based case control and case-crossover study.

PMID- 21192227
TI  - Transpedicular grafting after short-segment pedicle instrumentation for
      thoracolumbar burst fracture: calcium sulfate cement versus autogenous iliac bone
      graft.

PMID- 21192228
TI  - Correlation between CD4+ T-cell loss and Gag-specific T cells in different
      intestinal sites of chronically SIV-infected rhesus monkeys.
AB  - OBJECTIVE: To determine the loss of CD4+ T cells and virus-specific cytotoxic T
      cells (CTL) in different mucosal sites of rhesus monkeys infected with simian
      immunodeficiency virus (SIV). DESIGN: A cross-sectional comparative investigation
      of seven different mucosal sites from chronically SIV-infected rhesus monkeys was
      performed by analyzing blood and mucosal lymphocytes. METHODS: Mucosal
      lymphocytes were isolated from duodenum, jejunum, ileum and colon as well as from
      vagina, cervix and uterus of SIV-infected rhesus monkeys at necropsy. CD4+ T
      cells and SIV-Gag-specific CTL were determined in blood and mucosal samples by
      flow cytometry. RESULTS: A significant depletion of CD4+ T cells was observed in
      blood and all mucosal sites of SIV-infected rhesus monkeys compared to uninfected
      animals. But the mean percentage loss of CD4+ T cells varied between 66 and 95%
      between the different mucosal tissues. The frequency of CTL ranged between 0.4
      and 2.4% with the highest proportions in vagina and cervix. Among the intestinal
      sites the mean levels of CTL correlated with mean percentage loss of CD4+ T
      cells. CONCLUSION: A discriminative pronounced loss of CD4+ T cells among the
      mucosal tissues confirmed that viral replication affects different mucosal sites
      in a distinct way. Despite high levels of CTL, especially in vagina and cervix,
      the severe loss of mucosal CD4+ T cells could not be prevented during chronic SIV
      infection. However, within the four sites of the intestine a high virus-specific
      cellular immune response correlated with better preservation of CD4+ T cells.

PMID- 21192229
TI  - The role of mannose-binding lectin gene polymorphisms in susceptibility to HIV-1
      infection in Southern Brazilian patients.
AB  - OBJECTIVE: This study investigates the role of mannose-binding lectin (MBL) in
      the susceptibility to HIV-1 infection analyzing polymorphisms located at the MBL2
      promoter and exon 1 regions. MATERIALS AND METHODS: The prevalence of MBL2
      variant alleles was investigated in 410 HIV-1-infected patients from the South
      Brazilian HIV cohort and in 345 unexposed uninfected healthy individuals. The
      promoter variants were genotyped using polymerase chain reaction with sequence
      specific primers (PCR-SSP) and exon 1 variants were analyzed by real-time PCR
      using a melting temperature assay and were confirmed by PCR-restriction fragment
      length polymorphism (RFLP). MBL2 genotypic and allelic frequencies were compared
      between HIV-1-infected patients and controls using the chi-squared tests.
      RESULTS: The analyses were performed subdividing the individuals according to
      their ethnic origin. Among Euro-derived individuals a higher frequency of the
      LX/LX genotype was observed in patients when compared to controls (P < 0.001).
      The haplotypic analysis also showed a higher frequency of the haplotypes
      associated with lower MBL levels among HIV-1-infected patients (P = 0.0001).
      Among Afro-derived individuals the frequencies of LY/LY and HY/HY genotypes were
      higher in patients when compared to controls (P = 0.009 and P = 0.02).
      CONCLUSIONS: An increased frequency of MBL2 genotypes associated with low MBL
      levels was observed in Euro-derived patients, suggesting a potential role for MBL
      in the susceptibility to HIV-1 infection in Euro-derived individuals.

PMID- 21192230
TI  - Ongoing HIV-1 transmission among men who have sex with men in Amsterdam: a 25
      year prospective cohort study.
AB  - BACKGROUND: To examine the suggested resurgence of the HIV epidemic among men who
      have sex with men (MSM), we studied trends in HIV-1 incidence rates, sexual risk
      behaviour, risk factors for HIV-1 seroconversion, and source of HIV-1 infection
      among MSM in the Amsterdam Cohort Studies from 1984 to 2009. METHODS: Trends in
      HIV-1 incidence and risk factors for HIV-1 infection were studied using Poisson
      regression. Trends in sexual risk behaviour were evaluated using logistic
      regression, correcting for intra-individual correlation via generalized
      estimating equations. Trends in the source of HIV-1 infection were modelled via
      logistic regression. RESULTS: Of 1642 HIV-1-negative individuals, 217
      seroconverted during follow-up. HIV-1 incidence rates strongly decreased from
      8.6/100 person-years in 1985 to 1.3/100 person-years in 1992; remained relatively
      stable around 1.0/100 person-years between 1992 and 1996, and slowly increased to
      2.0/100 person-years in 2009 (P = 0.14; linear trend 1996-2009). Reports of
      unprotected anal intercourse (UAI) increased significantly from 1996 onwards. HIV
      1 seroconversion was associated with receptive UAI with casual partners, more
      than five sexual partners, a history of gonorrhoea (all in the preceding 6
      months), and a lower educational level. Currently, MSM are more likely to have
      contracted HIV-1 from casual partners than from steady partners, but trends of
      recent years suggest that steady partners became a growing source with increasing
      age. CONCLUSIONS: Following increases in sexual risk behaviour from 1996 onwards,
      HIV-1 continues to spread among MSM. Targeted prevention messages should continue
      to focus on sexual behaviour with casual partners, but also on sexual behaviour
      within steady relationships.

PMID- 21192232
TI  - Fifteen years of HIV surveillance among people who inject drugs: the Australian
      Needle and Syringe Program Survey 1995-2009.
AB  - OBJECTIVES: Following bipartisan political support in Australia for the timely
      introduction of needle and syringe programs (NSPs), HIV prevalence among people
      who inject drugs (PWID) remains low. This study aimed to determine the correlates
      of HIV infection among PWID; and to examine these correlates over time. DESIGN:
      Annual cross-sectional seroprevalence studies among attendees of sentinel NSP
      sites. METHOD: Multiple logistic regressions conducted on aggregated, de
      duplicated data from 1995 to 2009 to determine variables independently associated
      with HIV infection. RESULTS: Data were available for 22 478 individual NSP
      attendees, equating to a mean annual response rate of 44% (range 38-60%). Two
      thirds of participants were men, with a median age of 30 years, and a median of
      10 years since first injection. Eighty-five percent identified as heterosexual,
      10% as bisexual and 5% as homosexual. Serology was available for 21 248
      participants, of whom 230 (1.1%) tested HIV antibody positive. Variables
      independently associated with antibody seropositivity were homosexual or bisexual
      identity; male sex; older age; older age at first injection; and survey
      participation between 1995 and 1997 rather than later periods. CONCLUSIONS:
      Unlike settings in which evidence-based public health approaches to illicit drug
      policy are yet to be implemented, the epidemiology of HIV among NSP attendees
      mirrors that of Australia's general population, with the majority of exposures
      attributed to male-to-male sexual contact. This pattern has remained unchanged
      over 15 years despite significant variation in drug markets and patterns of drug
      use. NSPs also play a crucial role in this country's comprehensive HIV
      surveillance mechanisms.

PMID- 21192231
TI  - Effect of highly active antiretroviral therapy on biomarkers of B-lymphocyte
      activation and inflammation.
AB  - OBJECTIVE: Chronic inflammation and B-cell hyperactivation are seen in HIV
      infection, contributing to an increased risk for the accrual of genetic errors
      that may result in B-cell lymphoma. The primary objective of this study was to
      determine the effect of highly active antiretroviral therapy (HAART) on serum
      levels of molecules that are associated with immune activation and/or
      inflammation, including several that are associated with B-cell activation,
      specifically IL-6, sCD30, sCD27, IgG, IgA, CXCL13 (B lymphocyte chemoattractant,
      BLC), a B-lymphocyte chemokine involved in B-cell trafficking, as well as C
      reactive protein, an acute-phase protein. DESIGN: We used a retrospective cohort
      study design, measuring serum levels of these markers at each of four 1-year
      intervals, 2 years before and 2 years after HAART initiation, in a subgroup of
      290 HIV-infected men enrolled in the Multicenter AIDS Cohort Study (MACS).
      METHODS: Serum levels of immune activation-associated molecules were measured by
      ELISA and multiplexed immunometric assays. Reference values were determined by
      the 5th to 95th percentiles from a sample of 109 HIV-uninfected MACS men.
      RESULTS: HAART use was associated with a reduction, but not normalization, of
      most biomarkers tested. Serum levels of IL-6 and C-reactive protein appeared to
      be unaffected by HAART. CONCLUSIONS: These results suggest a partial
      normalization of serum cytokine levels post HAART. However, a chronic state of B
      cell hyperactivation continues 2-3 years after HAART initiation. These findings
      may explain, in part, the excess incidence of lymphoma still occurring in HIV
      infected persons in the post-HAART era.

PMID- 21192233
TI  - Effect on transmission of HIV-1 resistance of timing of implementation of viral
      load monitoring to determine switches from first to second-line antiretroviral
      regimens in resource-limited settings.
AB  - BACKGROUND: There is concern that antiretroviral therapy (ART) use with only
      clinical monitoring for failure will result in high rates of transmission of
      virus with resistance to drugs currently in use. METHODS: A stochastic simulation
      model of transmission of HIV, natural history and the effect of ART, was
      developed and used to predict the proportion of new infections with resistance
      according to whether and when viral load monitoring is introduced. RESULTS: In
      our base model, there was predicted to be 12.4% of new HIV infections with
      primary antiretroviral resistance in 2020 if clinical monitoring is used
      throughout, compared with 5.4 and 6.1% if viral load-guided switching (based on
      viral load measured every 6 months, with switch determined by a value >500
      copies/ml) was introduced in 2010 or 2015, respectively. The death rate for those
      on ART was lowest when viral load monitoring was used, but the overall death rate
      in all infected people was higher if viral load monitoring was introduced at the
      expense of scale-up in HIV diagnosis and ART initiation beyond their 2010
      coverage levels (4.7 compared with 3.1 per 100 person-years). INTERPRETATION: To
      preserve current first-line drugs for the long term there is an eventual need for
      some form of cheap and practical viral load monitoring in resource-limited
      settings. However, a delay in introduction of 5 years has limited consequences
      for resistance transmission so the current priority for countries' ART programmes
      is to increase HIV testing and provide treatment for all those in need of ART.

PMID- 21192234
TI  - The neuroanatomical substrate of lexical-semantic decline in MCI APOE epsilon4
      carriers and noncarriers.
AB  - Lexical-semantic competency in mild cognitive impairment (MCI) epsilon4 carriers
      was used as an endophenotype, and gray matter volume in MCI epsilon4
      carriers/noncarriers and in noncarrier controls was compared. Residual gray
      matter volumes were correlated with age of acquisition values for words from a
      category fluency task, an index of semantic competency. MCI patients had
      significantly impoverished lexical-semantic output compared with controls, more
      marked in MCI epsilon4 carriers. Smaller volumes in the left hippocampus,
      bilateral regions of the uncus, and posterior cingulate cortex were associated
      with a tendency to retrieve earlier acquired words in the category fluency task
      in MCI epsilon4 carriers, whereas poor semantic performance in MCI noncarriers
      was associated with smaller volumes in the left uncus, bilateral regions of the
      parahippocampal gyrus, and hippocampus, and also in a large number of neocortical
      regions. There was a significant semantic competency by genotype interaction in
      the left perirhinal cortex, in a number of left frontal and temporal areas and in
      the right inferior parietal lobule and precuneus. MCI epsilon4 carriers, when
      compared with noncarriers, had lower gray matter volume values confined to the
      right precuneus and the cerebellum bilaterally, but the converse comparison
      showed that MCI noncarriers had lower values in extensive frontal, temporal, and
      parietal regions of the neocortex. Similar brain volumetric variations linked to
      genotype were found in minimal-to-mild AD. The results suggest a relatively
      specific impact of apolipoprotein E (APOE) epsilon4 burden and underline the
      value of linguistic assessment in preclinical diagnosis.

PMID- 21192235
TI  - Differential impact of ApoE epsilon4 on cortical activation during famous face
      recognition in cognitively intact individuals and patients with amnestic mild
      cognitive impairment.
AB  - This study explores the neurofunctional correlates of the recognition of famous
      faces in patients with amnestic mild cognitive impairment (aMCI) and healthy
      controls depending on the genetic risk factor, Apolipoprotein E (ApoE) epsilon4.
      An event-related functional magnetic resonance imaging experiment was conducted
      while participants discriminated between famous and nonfamous faces. We compared
      the results of 32 healthy controls [17 ApoE epsilon4 carriers (E4+); 15
      noncarriers (E4-)] with those of 30 patients with aMCI (16 E4+; 14 E4-). Despite
      comparable task performance, patients with aMCI, E4+ showed significantly less
      activation in a large cortical network including the left parahippocampal gyrus
      than patients with aMCI E4-. Furthermore, in the aMCI group, we found
      significantly reduced activation in the left parahippocampal gyrus and posterior
      cingulate cortex compared with the control group. Our results show that critical
      regions of the brain show functional decline associated with major risk factors,
      such as ApoE epsilon4 allele and neuropsychological signs of aMCI for the
      development of Alzheimer disease. Importantly, the ApoE genotype seems to
      influence cortical activation in patients with aMCI and to a lesser degree in
      healthy controls as well, who are without any cognitive symptoms.

PMID- 21192236
TI  - Early onset dementia: characteristics in a large cohort from academic memory
      clinics.
AB  - AIM: To describe the characteristics of early-onset dementia (EOD) in a cohort
      from 3 memory clinics. METHODS: We assessed all patients with dementia referred
      to the Academic Memory Clinics at Amiens, Lille, and Rouen University Medical
      Centers between 2005 and 2007. Patients aged less than 65 years at the time of
      onset of symptom were included in the EOD group, whereas older patients were
      included in the late-onset dementia (LOD) group. RESULTS: Three thousand four
      hundred and seventy-three patients (including 1932 women) were included and 811
      (23.4%) were classified as EOD. The sex ratio was 1.12, whereas women were
      overrepresented in LOD (P=0.001). Patients with EOD were more frequently
      (P=0.001) living at home (87.3%), they had a lower educational level than the
      general population (P=0.0001) but were more educated (P=0.001). The current Mini
      Mental State Examination did not differ (P=0.3) between EOD (18.6+/-7.6) and LOD
      (18.9+/-6). The most common causes of EOD were Alzheimer's (22.3%) and vascular
      (15.9%) diseases and 4 pathologies that were significantly more frequent
      (P=0.001) than in the LOD group: frontotemporal dementia (9.7%), alcohol-related
      dementia (9.4%), traumatic brain injury (3.8%), and Huntington's disease (3%).
      CONCLUSIONS: EOD is characterized by specific features and different causes
      although Alzheimer's and vascular dementias remain the main causes of dementia in
      EOD.

PMID- 21192237
TI  - PF-04494700, an oral inhibitor of receptor for advanced glycation end products
      (RAGE), in Alzheimer disease.
AB  - OBJECTIVE: To evaluate the safety and tolerability of PF-04494700, an oral
      inhibitor of receptor for advanced glycation end products, in patients with mild
      to-moderate dementia of the Alzheimer type. METHODS: Patients aged 50 years and
      older who met the National Institute of Neurological and Communicative Diseases
      and Stroke/Alzheimer's Disease and Related Disorders Association criteria for
      Alzheimer disease with an Mini-Mental State Examination (MMSE) score between 12
      and 26 (inclusive) were randomized to 10 weeks of double-blind treatment with
      either a 10 mg "low dose" of PF-04494700 (after a 6-d loading dose of 30 mg/d), a
      20 mg "high dose" of PF-04494700 (after a loading dose of 60 mg/d), or placebo.
      Safety measures included adverse events, laboratory tests, vital signs, and 12
      lead electrocardiogram. RESULTS: Twenty-seven patients received PF-04494700 30/co
      mg (female: 63%; mean age: 74.6 y; mean MMSE: 21.1), 28 patients received PF
      04494700 60/20 mg (female: 57%; mean age: 76.6 y; mean MMSE: 21.6), and 12
      patients received placebo (female: 67%; mean age: 74.1 y; mean MMSE: 19.2). A
      higher proportion of patients completed 10 weeks of double-blind treatment on
      both the "low-dose" regimen of PF-04494700 (88.9%) and the "high-dose" regimen
      (85.7%) than patients who were on placebo (66.7%). Discontinuation owing to
      adverse events and incidence of severe adverse events, respectively, were lower
      in the "low-dose" regimen (7.4%, 11.1%) and the "high-dose" regimen (3.6%, 10.7%)
      compared with placebo (25.0%, 16.7%). There were no clinically meaningful
      differences in vital signs, laboratory test results, or mean electrocardiogram
      parameters in patients treated with PF-04494700. PF-04494700 had no consistent
      effect on plasma levels of beta-amyloid, inflammatory biomarkers, or secondary
      cognitive outcomes. CONCLUSIONS: Ten weeks of treatment with PF-04494700 was safe
      and well tolerated in patients with mild-to-moderate Alzheimer disease,
      indicating the feasibility of a larger long-term efficacy trial.

PMID- 21192238
TI  - Assessment of nondeclarative learning in severe Alzheimer dementia: the Implicit
      Memory Test (IMT).
AB  - Although patients with Alzheimer dementia (AD) have impaired explicit memory,
      more automatic, implicit aspects of learning and memory may be relatively
      preserved. However, neuropsychological tests for the assessment of implicit
      memory are lacking. This study examines a newly developed test, the Implicit
      Memory Test, in 28 patients with severe AD (mini-mental state examination 5 to
      12) and 22 cognitively unimpaired matched controls (mini-mental state examination
      25 to 29). The Implicit Memory Test consists of visually presented word (stem
      completion) and picture (fragmented picture identification) subtests, each
      comprising 3 learning trials and a delayed test. Explicit memory was also
      assessed, using the verbal paired-associate learning subtest from the Wechsler
      Memory Scale and the Visual Association Test. Patients with AD obtained a floor
      performance on both explicit memory tests, whereas a significant learning curve
      was found for both the stem-completion and the fragmented pictures subtests of
      the Implicit Memory Test. Delayed testing on the fragmented pictures subtest
      showed a preserved performance that may have been mediated by implicit learning.
      Delayed performance on the stem-completion subtest, however, showed clear memory
      decay that suggests contamination by explicit memory function, at least in the
      controls. These findings extend the earlier results on word-stem completion and
      fragmented picture identification in patients with mild-to-moderate AD and
      indicate that residual learning capacity can be assessed in severe AD.

PMID- 21192239
TI  - Caregiver burden and neuropsychiatric symptoms in older adults with cognitive
      impairment: the Aging, Demographics, and Memory Study (ADAMS).
AB  - OBJECTIVES: To estimate the quantity of informal care associated with
      neuropsychiatric symptoms in older adults with cognitive impairment. DESIGN:
      Cross-sectional analysis. SETTING: The Aging, Demographics, and Memory Study.
      PARTICIPANTS: A sample (n=450) of adults aged 71 years and older with cognitive
      impairment drawn form the Health and Retirement Study. MEASUREMENTS: The presence
      of neuropsychiatric symptoms (delusions, hallucinations, agitation, depression,
      apathy, elation, anxiety, disinhibition, irritation, and aberrant motor
      behaviors) was identified using the neuropsychiatric inventory. Cognitive
      category [normal, cognitive impairment without dementia (CIND), or dementia] was
      assigned by a consensus panel. The hours per week of active help and supervision
      were ascertained by informant questionnaire. RESULTS: Among older adults with
      CIND or dementia, those with no neuropsychiatric symptoms received an average of
      10.2 hours of active help and 10.9 hours of supervision per week from informal
      caregivers. Those with 1 or 2 neuropsychiatric symptoms received an additional
      10.0 hours of active help and 12.4 hours of supervision per week, while those
      with 3 or more symptoms received an additional 18.2 hours of active help and 28.7
      hours of supervision per week (P<0.001). The presence of irritation (14.7
      additional hours) was associated with the greatest number of additional hours of
      active help. The presence of aberrant motor behaviors (17.7 additional hours) and
      disinhibition (17.5 additional hours) were associated with the greatest number of
      additional hours of supervision. CONCLUSIONS: Neuropsychiatric symptoms among
      those with CIND or dementia are associated with a significant increase in the
      provision of informal care. This care represents a significant time commitment
      for families and a significant economic cost to society.

PMID- 21192241
TI  - A new estradiol-dienogest oral contraceptive marks "The Pill's" 50th anniversary.
AB  - Oral contraceptive pills were first approved by the Food and Drug Administration
      50 years ago. Discovery of the physiology of reproduction and demonstration of
      the ability to inhibit ovulation with ovarian extracts laid the early groundwork
      for the development of contraceptives. Later, characterization of the hormones
      controlling ovulation and synthesis of progestins allowed production of oral
      contraceptives. Modern estrogen and progestin pills have undergone significant
      changes since their initial introduction. New formulations have been developed,
      doses have been lowered, and extended use introduced. The Food and Drug
      Administration has recently approved a new oral contraceptive containing
      estradiol valerate and dienogest. This pill contains an orally active estradiol
      in combination with a progestin with strong endometrial activity. The decreasing
      estrogen dose combined with an increasing progestin dose decreases the risk of
      break through bleeding when compared to previous estradiol valerate formulations.
      The contraceptive efficacy and a tolerability of this new pill are similar to
      currently marketed low dose combined estrogen-progestin oral contraceptives.

PMID- 21192240
TI  - Risk of decline in functional activities in dementia with Lewy bodies and
      Alzheimer disease.
AB  - We examined the risk of 1-year decline in 4 everyday activities in patients with
      dementia with Lewy bodies (DLB), relative to patients with Alzheimer disease
      (AD). Data were from the National Alzheimer's Coordinating Center, gathered from
      32 Alzheimer's Disease Centers. Participants (n=1880) were: aged 60+ years,
      demented with a primary clinical diagnosis of probable AD or DLB, and had a
      global Clinical Dementia Rating of 0.5 to 2. The activities were measured with
      the Functional Activities Questionnaire. In modified Poisson regression models
      adjusted for demographics, baseline activity, years from symptom onset, cognitive
      impairment, and comorbidities; DLB participants aged 67 to 81 years had 1.5 to 2
      times increased risk of decline in performing basic kitchen tasks, engaging in
      games/hobbies, and paying attention/understanding, relative to AD participants of
      the same age (P<0.05). There was no significant difference between AD and DLB
      participants beyond this age range. For decline in ability to go shopping alone,
      there was also no significant difference between AD and DLB participants. In
      summary, the functional course of DLB, relative to AD, may depend on the age of
      the patient. These findings may provide anticipatory guidance to families and
      healthcare providers, which may be useful in the planning of care strategies.

PMID- 21192242
TI  - Statin-associated rhabdomyolysis with acute renal failure complicated by
      intradialytic NSTEMI: a review of lipid management considerations.
AB  - Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are
      associated with myopathy, myalgias, myositis, and rhabdomyolysis. Rhabdoymyolysis
      is a rare complication and may cause acute renal failure, which may be fatal. In
      such cases, alternative therapies should be considered. In this review, we
      attempted to elucidate the lipid management options in patients with
      rhabdomyolysis and coronary artery disease. We also describe a case report of a
      patient who developed rhabdomyolysis from dual antilipid therapy followed by
      acute renal failure and non-ST elevation myocardial infarction. Such a complex
      case has not been reported in the literature, and lipid management options may
      include niacin, omega 3-fatty acids, or bile acid sequestrants. Once alternative
      therapies are initiated, monitoring a patient closely with evaluation for
      associated adverse events should be performed.

PMID- 21192243
TI  - Multidrug resistant pneumonia treated with aerosolized amikacin in a patient with
      acute renal insufficiency.
AB  - Multidrug resistant pneumonia is an entity, which is difficult to treat, and in a
      patient with acute renal insufficiency, it leaves a physician with a handful of
      antibiotics to be considered. Aerosolized administration of antibiotics is one
      option that can be contemplated for a patient with acute renal insufficiency to
      avoid the nephrotoxic effect of the antibiotics. 

PMID- 21192244
TI  - Therapeutic efficacy of artesunate-amodiaquine combinations and the plasma and
      saliva concentrations of desethylamodiaquine in children with acute uncomplicated
      Plasmodium falciparum malaria.
AB  - The treatment efficacy of artesunate-amodiaquine (AQ) coformulated or copackaged,
      and the plasma and saliva concentrations of desethylamodiaquine (DEAQ), the
      active metabolite of AQ, were evaluated in 120 and 7 children, respectively, with
      uncomplicated Plasmodium falciparum malaria treated with oral daily doses of the
      2 formulations for 3 days. All children recovered clinically. Fever clearance
      (1.1 +/- 0.2 vs 1.0 +/- 0 days) and parasite clearance times (21.1 +/- 10.2 vs
      19.0 +/- 7.0 hours) in artesunate-AQ coformulated and artesunate-AQ copackaged
      treated children, respectively, were similar. All children remained aparasitemic
      for at least 28 days. Blood and saliva samples were collected over 35 days and
      DEAQ in plasma and saliva was determined by high-performance liquid
      chromatography. DEAQ was detectable in plasma and saliva within 40 minutes of
      oral administration of artesunate-AQ. DEAQ concentrations 7 days after the start
      of therapy were 247.8 and 125.1 ng/mL in plasma and saliva, respectively. The
      concentration-time curves of plasma and saliva in declining phases were
      approximately parallel giving a similar half-life of 169.1 +/- 16.4 and 142.8 +/-
      6.5 hours in plasma and saliva, respectively. Clearance from plasma and saliva
      was also similar (335.6 and 443.4 mL.h.kg, respectively). Area under
      concentration-time curves (AUC0-35d) for plasma and saliva were 94,744.9 and
      74,004.2 ng.mL.h, respectively. In general, Saliva-plasma concentration ratio was
      0.25-0.4. DEAQ concentrations in saliva may be useful for monitoring therapy and
      for the evaluation of the disposition of AQ in children with falciparum malaria
      treated with AQ-based combination.

PMID- 21192245
TI  - Can a poison center overdose guideline safely reduce pediatric emergency
      department visits for unintentional beta-blocker ingestions?
AB  - Poisoning is a leading cause cause for injury and death in pediatric patients.
      For this reason, beta-blocker ingestion has been an indication for emergency
      department (ED) referral and evaluation in pediatric patients even though
      significant clinical effects are uncommonly reported. We sought to determine
      whether an evidence-based triage guideline developed jointly by the American
      Association of Poison Control Centers, American Academy of Clinical Toxicology,
      and American College of Medical Toxicology safely reduces unnecessary pediatric
      ED visits after unintentional small dose beta-blocker overdose. This was a
      prospective study of patients aged 0-6 years with a beta-blocker ingestion
      managed by a regional poison center pre and postimplementation of the triage
      guideline. One hundred fifty-three cases met inclusion criteria. Before
      implementation of an evidence-based triage guideline for out-of-hospital
      management, 52 (67%) cases were referred for ED evaluation, and 26 (33%) cases
      were recommended for home observation. After guideline implementation, 38 (51%)
      cases were referred for ED evaluation, and 37 (49%) were recommended for home
      observation. No deaths occurred in either group. The triage guideline was
      accurately followed by poison center staff in 96% of cases after implementation.
      An out-of-hospital triage guideline for pediatric beta-blocker overdose was
      accurately followed by poison center staff and safely reduced unnecessary ED
      referrals with a 50% increase in home observation.

PMID- 21192246
TI  - Management of refractory ascites.
AB  - Ascites that does not respond or recurs after high-dose diuresis and sodium
      restriction should be considered refractory ascites. As cirrhosis advances, the
      escaping fluid overwhelms the lymphatic return. Decrease in renal plasma flow
      leads to increased sodium reabsorption at the proximal tubule leading to
      decreased responsiveness to loop diuretics and mineralocorticoid antagonists,
      which work distally. These complex hemodynamic alterations lead to refractory
      ascites. In refractory ascites, high-dose diuresis (400 mg of spironolactone and
      160 mg of furosemide) and sodium restriction (<90 mmol/d) result in inadequate
      weight loss and sub optimal sodium excretion (<78 mmol/d). Further use of
      diuretics is limited by complications such as encephalopathy, azotemia, renal
      insufficiency, hyponatremia, and hyperkalemia. Therapy for refractory ascites is
      limited. The available therapies are repeated large volume paracentesis (LVP),
      transjugular intrahepatic portosystemic shunts, peritoneovenous shunts,
      investigational medical therapies, and liver transplantation. LVP with
      concomitant volume expanders is the initial treatment of choice. Transjugular
      intrahepatic portosystemic seems to be superior to LVP in reducing the need for
      repeated paracentesis and improves the quality of life. Several treatments that
      act at different steps in the pathogenesis of ascites are investigational, and
      some show promising results. Splanchnic and peripheral vasoconstrictors
      (Octreotide, Midodrine, and Terlipressin) increase effective arterial volume and
      decrease activation of the renin-angiotensin system with resultant increase in
      renal sodium excretion. Clonidine when given with spironolactone has been shown
      to cause rapid mobilization of ascites by significantly decreasing the
      sympathetic activity and renin-aldosterone levels. Natural aquaretics and
      synthetic V2 receptor antagonists (satavaptan) are being evaluated for
      mobilization of ascites by increasing the excretion of solute-free water. Liver
      transplantation remains the only definitive therapy for refractory ascites.
      Because refractory ascites is a poor prognostic sign, liver transplantation
      should be considered and incorporated early in the treatment plan.

PMID- 21192247
TI  - A unique paradoxical reaction to tuberculosis therapy: case report and brief
      review of the literature.
AB  - Extensive experience in the diagnosis and treatment of tuberculosis (TB) has led
      to treatment guidelines, which almost always result in progressive clinical
      improvement and cure in the compliant patient. Failure of a patient to respond as
      expected raises concerns of unexpected drug resistance, poor absorption, drug
      fever, or rarely an intense inflammatory reaction known as paradoxical reaction.
      Paradoxical reactions to anti-TB treatment are relatively rare in
      nonimmunocompromised individuals. Hepatic abscess is a very rare consequence of
      primary TB infection but has never been described as occurring as part of a
      paradoxical reaction. We present a case of a unique paradoxical reaction to
      initiation of TB treatment. 

PMID- 21192248
TI  - Differentiation of arginine vasopressin antagonistic effects by selective V2
      versus dual V2/V1a receptor blockade in a preclinical heart failure model.
AB  - Arginine vasopressin (AVP) is increased in patients with heart failure (HF). Its
      actions are linked to free water reabsorption (V2-) and arteriolar
      vasoconstriction (V1a receptor). AVP can exacerbate the cardiorenal syndrome with
      excess fluid retention and afterload increase. Tolvaptan (TOL; selective V2
      antagonist) and Conivaptan (CON; dual V1a/V2 antagonist) are two AVP antagonists
      that counteract the action of AVP with distinct profiles. We investigated the
      therapeutic effects of CON and TOL in an acute HF model. Mongrel dogs were paced
      continuously at 220 beats/min. After 14 days, the animals underwent acute
      testing. Dogs were instrumented to measure cardiac output, blood pressure,
      pulmonary artery pressure, and left ventricular dP/dtmax. Additionally, during
      the acute experiments, vasopressin was infused intravenously (4 mU/kg/min) to
      achieve constant and controlled pathophysiological levels of AVP. Subsequently,
      animals received either CON or TOL (n = 6; 0.1-mg/kg bolus). There were no
      significant differences in effect on mean arterial pressure, dP/dtmax, central
      venous pressure, and urine output between CON and TOL. In contrast, cardiac
      output increased by 0.15 l/min after CON and decreased by 0.6 l/min after TOL (P
      < 0.01). Accordingly, the total peripheral resistance increased after TOL by 250
      dyn*s/cm and decreased after CON by 125 dyn*s/cm (P < 0.01). In conclusion, it
      was demonstrated that in an acute HF model, CON lowered, whereas TOL increased
      afterload. The results suggest that dual V1a/V2 blockade in the acute HF setting
      could be beneficial compared with selective V2 blockade. Chronic experiments are
      needed to determine whether this finding can translate into a sustained clinical
      advantage.

PMID- 21192249
TI  - Neuroplasticity and its applications for rehabilitation.
AB  - Stroke represents a major cause of death and disability. In just the last two
      decades, science has begun to appreciate the central nervous system's attempts to
      repair itself through a process termed neuroplasticity. The remodeling is a
      dynamic process subject to endogenous and exogenous forces. Rehabilitation has
      started to implement approaches based on objective measures such as diffusion
      tensor imaging and functional magnetic resonance. Newer modalities such as
      constraint-induced movement therapy and robotic interventions are being used for
      both short- and long-term functional gains. This review describes the various
      studies on neuroplasticity and the variety of interventions now available.

PMID- 21192251
TI  - Changes in von Willebrand factor and ADAMTS13 during IVF.
AB  - During IVF, circulating estradiol concentrations are strongly increased, and this
      may have direct effects on hemostasis. Elevated von Willebrand factor levels
      represent an important risk factor for arterial and venous thrombosis. ADAMTS13,
      also known as von Willebrand factor-cleaving protease, has an important
      regulatory function of von Willebrand factor but has not been studied during IVF.
      Blood was sampled from 31 women at maximal downregulation of estradiol synthesis
      using gonadotropin-releasing hormone analogues and during high-level stimulation
      of estradiol synthesis using follicle-stimulating hormone during the first phase
      of IVF. Von Willebrand factor antigen, von Willebrand factor ristocetin cofactor
      activity, factor VIII and ADAMTS13 antigen and activity levels in plasma were
      determined at the time of downregulation and at high-level stimulation. Estradiol
      increased from a mean of 154 pg/ml at downregulation to 5889 pg/ml at high-level
      stimulation (range 1620-19 500 pg/ml). Factor VIII increased from 0.96 +/- 0.34
      to 1.26 +/- 0.41 kIU/l (P < 0.001). Von Willebrand factor antigen and activity
      increased from 0.75 +/- 0.22 to 1.06 +/- 0.40 kIU/l (P < 0.001) and from 0.83 +/-
      0.26 to 1.24 +/- 0.48 kIU/l (P < 0.001), respectively. ADAMTS13 antigen decreased
      from 72.2 +/- 13.5 to 67.9 +/- 9.9% (P < 0.05, P = 0.01) and ADAMTS13 activity
      from 88.6 +/- 18.3 to 80.8 +/- 15.7% (P < 0.01). The increments in estradiol and
      factor VIII during IVF were paralleled by an increase in von Willebrand factor
      antigen and activity, and a decrease in circulating ADAMTS13 antigen and
      activity, respectively. This could in part explain why these patients have an
      increased risk of thrombotic events.

PMID- 21192252
TI  - Low molecular weight heparin versus no treatment in women with previous severe
      pregnancy complications and placental findings without thrombophilia.
AB  - Low molecular weight heparin (LMWH) treatment has been recommended for pregnant
      women with previous adverse pregnancy and who were diagnosed as having a
      thrombophilia. We now examined the effect of LMWH on pregnant women without
      thrombophilias who had severe pregnancy complications and placental vasculopathy
      in an earlier pregnancy. Seventy-two women with a history of severe preeclampsia,
      fetal growth restriction (FGR) less than fifth percentile, severe placental
      abruption and/or stillbirth after 20 weeks, whose thrombophilia workup was
      negative, were enrolled. Placental vasculopathy was defined as villous infarcts,
      fibrinoid necrosis of decidual vessels, fetal vessel thrombosis, evidence of
      placental abruption and perivillous fibrin deposition. The study group consisted
      of 32 pregnant women who were treated with LMWH and 40 pregnant women who were
      not treated with LMWH (control group) in their ensuing pregnancy in our
      institution between 2003 and 2007. The incidences of severe preeclampsia, FGR,
      placental abruption and stillbirth in the previous pregnancies were similar for
      both groups. The incidences of severe preeclampsia and placental abruption in the
      study group in the index pregnancy were significantly lower than the control
      group (3.13 versus 20%, P = 0.03; and 0 versus 15%, P = 0.03, respectively). The
      respective incidence of FGR was 6.25 versus 22.5%, and of overall adverse outcome
      was 9.4 versus 60% (P = 0.001). Treatment with LMWH may reduce the rate of the
      recurrence of severe pregnancy complications and significant placental
      vasculopathy in women without thrombophilias.

PMID- 21192253
TI  - Genetic analysis of a pedigree with combined factor XII and factor XI deficiency.
AB  - The objective of the present study was to identify the gene mutations of factor
      XI (FXI) and factor XII (FXII) in a Chinese pedigree with combined congenital FXI
      and FXII deficiencies. The proband was a 40-year-old woman with deficiency in
      both FXI (49%) and FXII (0%) activities. Blood samples from 10 other members of
      her family were collected and used for detection of FXI, FXII activities (FXI: C,
      FXII: C) and antigen levels. Genetic analysis to detect mutations in FXI, FXII
      genes was also performed. The proband's mother, three brothers, two sisters, her
      son and her daughter all have lowered FXII: C. Furthermore, her mother and one of
      her brothers also have lowered FXI: C. Gene sequencing for FXI in affected
      members revealed a heterozygous C23179T point mutation in exon 11 resulting in
      substitution of arginine 396 by cysteine. Gene sequencing for FXII revealed a
      C46T in the promoter region and a deletion mutation of two nucleotides CA at
      position 9160 and 9161 in exon 5. The deletion mutation can lead to frameshift
      mutation and premature termination of transcription in exon 6. We found a new
      heterozygous missense mutation in the FXI gene and a new nonsense mutation of two
      nucleotides deletion which caused frameshift mutation and premature termination
      of transcription in the FXII gene in a Chinese family with combined FXI and FXII
      deficiencies.

PMID- 21192254
TI  - Evidence for age-related differences in human fibrinogen.
AB  - Fibrinogen has previously been demonstrated to exist in a 'fetal' form, in cord
      blood of term infants, with increased sialic acid content compared to adult
      fibrinogen. The functional implications of these differences are reflected in
      prolonged thrombin clotting times in newborns as well as differences in
      polymerization of fibrin from 'fetal' fibrinogen. Despite numerous studies of
      fibrinogen structure and function, the age at which 'fetal' fibrinogen reverts to
      the adult form, as well as the physiological significance of this phenomenon
      remains unknown. This study was designed to determine whether the difference
      between the 'fetal' and the 'adult' fibrinogen molecule persists in a 'childhood'
      form throughout progression from infancy to adulthood. The results demonstrate
      that although the concentration of fibrinogen from day 1 neonates is decreased
      compared to adult fibrinogen, functional activity of this protein is comparable
      in both age groups. In addition, despite there being quantitatively less
      fibrinogen in day 3 and 11-16-year age groups, this protein is functionally more
      active compared to adult fibrinogen. In addition, the molecular weight of the
      Aalpha fibrinogen chain was consistently higher by up to 1500 Da in neonates and
      children compared to adults, suggesting age-specific differences in
      posttranslational modification of this chain of the protein.These age-related
      differences in fibrinogen could provide a protective mechanism against excessive
      polymerization and proteolysis of this protein, providing a possible explanation
      of the thromboprotective mechanism that is functioning in neonates and children.

PMID- 21192255
TI  - Analytic variability due to change of deficient plasma vials: application to one
      stage clotting factor VIII assay.
AB  - The statistical process control required under International Organization for
      Standardization 15189 as well as economic considerations necessitates having
      robust methods that do not need systematic recalibration for each series of
      analyses. Using the concrete example of one-stage clotting factor VIII assay, we
      assessed the analytic variability specifically linked to changing factor VIII
      deficient plasma vials. The study used freeze-dried (Instrumentation Laboratory,
      Siemens, Stago and T-Coag) and frozen (Affinity Biologicals and Precision
      Biologic) factor VIII deficient plasmas. On the most widely recognized
      acceptability criteria and methods (i.e. those of Kallner et al. and Kasper et
      al.), the Stago and Instrumentation Laboratory plasmas require systematic
      recalibration at each vial changeover.

PMID- 21192256
TI  - The economics of glycemic control in the ICU in the United States.
AB  - PURPOSE OF REVIEW: Currently the USA has an aging population, with increasing
      deficits and a healthcare system that most would agree is in need of repair.
      Finding ways to curtail costs is urgently needed. Attention to glycemic control
      and metabolic care offers a cost-effective method of treatment to reduce
      complications. RECENT FINDINGS: Healthcare-related expenses occupy an expanding
      portion of gross domestic product in the US and are a driver of the deficit.
      Despite all of this spending, the US receives average marks on outcomes and is
      not obtaining value in its healthcare. Any movements toward healthcare reform
      must focus on improving outcomes per healthcare dollar spent, and increasing
      value. The Affordable Care Act will place greater emphasis on preventing
      complications and reducing hospital-acquired infections. The original Leuven
      trial demonstrated that proper implementation of glycemic control can reduce
      morbidity and mortality. More recent studies have shown that there is a cost
      benefit to glycemic control as well, through reduction of hospital stay and
      prevention of complications. On the basis of these changes, physicians who
      practice metabolic care and provide glycemic control are well positioned to add
      value in this era of healthcare reform. SUMMARY: Glycemic control is inherently
      valuable in the care of ICU patients as it decreases infectious complications,
      reduces lengths of stay, and has a positive effect on morbidity and mortality.
      Further studies should be completed to delineate the exact amount of cost-savings
      that can be obtained by proper implementation of glycemic control in the ICU.

PMID- 21192257
TI  - Lipids for parenteral nutrition in neonates.
AB  - PURPOSE OF REVIEW: In neonatal intensive care units, the interest and scope for
      research in the field of intravenous lipids has significantly widened in recent
      years. This brief review covers the advances in this field in the last 2 years.
      RECENT FINDINGS: These include a significant amount of research in evaluating
      safety and efficacy of novel lipid emulsions that include olive oil or fish oil.
      Short-term studies involving novel lipid emulsions have documented safety and
      benefits in terms of reduced inflammation and lipid peroxidation. Fish oil-based
      lipid emulsions have also been used to prevent and treat parenteral nutrition
      induced cholestasis. Other areas of progress include stability studies of all-in
      one parenteral nutrition mixtures including lipid emulsions for neonates.
      SUMMARY: Since the first soybean oil-based lipid emulsions were introduced 50
      years ago, progress has been made in understanding the composition, dose and
      clinical effects of parenteral lipids in neonatal patients. However there is a
      paucity of data in terms of definitive head-to-head trials of different novel
      lipid emulsions evaluating short-term as well as long-term clinically important
      outcomes including neurodevelopment. Future research is required to determine
      long-term benefits of novel lipid emulsions for neurological outcome and effects
      on the immune system.

PMID- 21192258
TI  - Malassezia virulence determinants.
AB  - PURPOSE OF REVIEW: Malassezia yeasts are associated with a number of dermatologic
      and systemic diseases in humans and animals. Pityriasis versicolor is amongst
      these diseases and represents one of the most common human skin diseases. Beyond
      that, the role of Malassezia yeasts in the pathogenesis of other skin diseases
      such as psoriasis, seborrheic dermatitis and confluent and reticulate
      papillomatosis is discussed but remains less clear. Clear pathogenetic mechanisms
      of the above-mentioned diseases are not known so far. The review presents new
      findings on virulence factors of Malassezia yeasts, shedding light on the
      pathogenesis of Malassezia-associated diseases. RECENT FINDINGS: Several
      virulence factors in Malassezia yeasts are known, based on their enzymatic
      lipolytic activity resulting in the production of distinct metabolites and
      special cell wall features. Recently, a secondary metabolic pathway possibly
      implicated in the pathogenesis of pityriasis versicolor was described. SUMMARY:
      The article presents virulence factors of Malassezia yeasts ranging from irritant
      metabolic byproducts to highly bioactive indole derivatives and attempts to
      clarify their pathogenic implications in the different diseases. Special emphasis
      is given to the pathogenesis of pityriasis versicolor, as it represents the
      disease wherein the causative relationship with Malassezia yeasts appears the
      most obvious.

PMID- 21192259
TI  - Balamuthia mandrillaris infection of the skin and central nervous system: an
      emerging disease of concern to many specialties in medicine.
AB  - PURPOSE OF REVIEW: Balamuthia mandrillaris infection of the skin and central
      nervous system has been increasingly reported in the last decade, making this
      entity a genuine emerging disease. The ability of the clinician in recognizing
      the skin lesion early in the course of the disease may lead to a successful
      therapeutic intervention in an otherwise fatal disease. RECENT FINDINGS: In the
      past years, advances have been made regarding knowledge about the ubiquity of the
      ameba in the environment, its worldwide distribution (with higher prevalence in
      South America), the patients at risk (particularly those of Hispanic origin), the
      diagnostic methods (including those based on molecular biology) and the different
      therapeutic strategies that have resulted in survival of patients. A recent
      report dealing with organ transplant transmission of this infection has made it a
      subject of interest in transplant medicine. SUMMARY: The present review will
      allow readers from different fields (clinician, dermatologist, neurologist,
      infectious disease and transplant specialist) to become familiar with the
      clinical aspect of the disease, including diagnosis and therapy.

PMID- 21192260
TI  - Hidradenitis suppurativa: a review of cause and treatment.
AB  - PURPOSE OF REVIEW: Hidradenitis suppurativa is a chronic or relapsing
      inflammatory cutaneous disorder manifested by recurrent formation of abscesses,
      fistulating sinus and scarring in the apocrine-gland-bearing skin. This review
      discusses the different aetiological theories and management opportunities.
      RECENT FINDINGS: Current understanding of the pathogenesis suggests that
      hyperkeratosis of the infundibulum, leading to follicular occlusion of the
      pilosebaceous unit plays a role. Bacterial infection with staphylococci,
      Escherichia coli and streptococcus is considered as a secondary event in the
      pathogenesis. Smoking and obesity are both known as risk factors and are
      associated with more severe disease course. Recently, more attention has been put
      into the understanding of the immunopathology of the skin and the results
      indicate that hidradenitis suppurativa may be considered as an inflammatory
      disease of unknown cause based on a defect in the hair follicle immunity. The
      treatments are most appropriately chosen on the basis of disease severity and the
      existence of any associated risk factors or comorbidities. There are three levels
      in the management of hidradenitis suppurativa: topical options, systemic options
      and surgical methods including laser therapy. At each level several treatment
      principles have shown themselves to be efficient, and may therefore be used
      either alone or in combination. Therapies are generally effective against
      microorganisms, inflammation or infundibular hyperkeratosis. Where an
      antimicrobial therapy is used, the drugs used often have significant additional
      immunomodulatory effects. SUMMARY: The recent studies give us a better insight
      into the pathogenesis of hidradenitis suppurativa and should translate into
      improved therapies.

PMID- 21192261
TI  - RAF inhibition and induction of cutaneous squamous cell carcinoma.
AB  - PURPOSE OF REVIEW: Targeted anticancer agents are associated with frequent skin
      side-effects. Several kinase inhibitors have been implicated in the appearance of
      borderline and malignant skin tumors such as keratoacanthomas and squamous cell
      carcinomas. The purpose of this review is to discuss the mechanisms as well as
      the management and implications of this unexpected side-effect. RECENT FINDINGS:
      Recent findings suggest that these skin neoplasms are due to RAF inhibition and
      that they are more frequent and arise earlier after treatment initiation with the
      more specific and potent RAF inhibitors than with the multikinase and pan-RAF
      inhibitor sorafenib. Biological results show that RAF inhibition induces
      paradoxical activation of the MAPK (mitogen-activated protein kinase) signaling
      pathway in cells that do not carry BRAF mutation. SUMMARY: This review discusses
      the various mechanisms that could be implicated in the appearance of skin tumors
      during the course of anti-RAF treatments as well as the implications of these
      findings for clinical practice and future drug development. The unexpected
      emergence of tumors during the course of anticancer therapies is a concern that
      stimulates an active field of research in the aim of understanding the underlying
      mechanisms and preventing if possible skin tumor initiation.

PMID- 21192262
TI  - Immunotherapy for melanoma.
AB  - PURPOSE OF REVIEW: Melanoma therapy has recently seen significant progress, with
      several new drugs in phase II/III trials showing promising results. In this
      review, we discuss the most promising immunotherapies either already established
      or being developed, concentrating on agents for which there are high-level data
      to support or refute their role in treating this disease. This topic is timely,
      given the lengthy list of immune checkpoint inhibitors and vaccine formulations
      in development for melanoma. RECENT FINDINGS: The discovery of immune checkpoint
      proteins like CTLA-4, PD-1 and CD40 and the development of antibodies and small
      molecules that either inhibit or promote their activity has lent a huge impetus
      to the immunotherapy of melanoma. The development of vaccines that include
      agonists of various immune signaling like the MAGE-3 ASCI has also revived the
      field of cancer vaccines. Melanoma is the 'poster child' for immunotherapy of
      cancer, since a recent randomized phase III trial showed a survival benefit for
      immunotherapy. SUMMARY: The burgeoning field of immunotherapy for melanoma has
      important implications for clinicians, and for the novel paradigms of treatment
      and response assessment that immunotherapies will promote. The unique side-effect
      profile for immune checkpoint inhibitors will be a challenge but new skills for
      dealing with them in community based practice will be learned. The concept that
      physicians might see late regression, or progression followed by regression will
      cause a sea-change in the way patients are treated, since treating beyond
      progression may be suitable in some cases using immunotherapy.

PMID- 21192263
TI  - Epidemiological evidence that UVA radiation is involved in the genesis of
      cutaneous melanoma.
AB  - PURPOSE OF REVIEW: Epidemiological data have contributed to the classification in
      2009 of the full ultraviolet (UV) radiation spectrum as carcinogenic to humans.
      We reviewed the epidemiological evidence that UVA could be involved in the
      genesis of cutaneous melanoma. RECENT FINDINGS: Use of artificial UV tanning
      devices (sunbeds) consists mainly of repeated exposure to high UVA doses.
      Epidemiological studies published over the last years confirmed the association
      between sunbed use and melanoma. Sunbed use is the most probable cause of an
      epidemic of melanoma that took place in Iceland from 1990 to 2006. The four-fold
      increase in melanoma incidence was not followed by an increase in melanoma
      mortality. Sunscreens were primarily devised for the prevention of sunburn, and
      UVB is the wavelength causing most sunburns. All observational studies and
      randomized trials show that sunscreen use may extend sun exposure intended for
      getting a tan, while it does not necessarily decrease sunburn occurrence.
      Sunscreen use for tan acquisition would thus lead to similar exposure to UVB and
      greater exposure to UVA, which could explain the slightly higher melanoma risk
      often found among sunscreen users. SUMMARY: UVA could be involved in the
      occurrence of nonlife-threatening melanoma. The increasing use of sunbeds and of
      sunscreens may partly explain why melanoma incidence increases in most light
      skinned populations without concomitant increase in mortality.

PMID- 21192264
TI  - Economic considerations of the diagnosis and management for glaucoma in the
      developed world.
AB  - PURPOSE OF REVIEW: This review evaluates the last 18-month literature related to
      costs and glaucoma. The emphasis is to look at evidence as a big picture and
      evaluate the critical points and challenges in methodology, current knowledge and
      future research. RECENT FINDINGS: On the basis of simulation models, treating
      glaucoma appears to be cost-effective compared with no treatment. The results of
      the simulation models are, however, not consistent regarding when to treat ocular
      hypertension and when comparing different therapeutic interventions. Most models
      simulated starting treatment with prostaglandins compared with other medications,
      whereas one study simulated also initial laser therapy which appeared to be cost
      saving compared with medical therapy. The models utilized input data both from
      randomized controlled trials (ideal outcomes) and observational studies (with
      incomplete and selective reporting). Models suffer from unreliability of data,
      for example data from randomized diagnostic trials, empirical data of utility
      values and glaucoma-induced visual disability are limited. SUMMARY: As the number
      of economic evaluations increases, the interpretation and evaluation of their
      extensive reporting appears very challenging. The published studies highlight the
      range of uncertainties due to the shortages of our current knowledge and
      evidence. There is a need for reliable and 'realistic' data for economic
      evaluations, preferably data from pragmatic randomized trials of 'usual
      patients'. Similar to emphasizing the cost-effectiveness of care, there is a need
      to evaluate the expected payback and cost-effectiveness of research
      interventions. However, even high-quality evidence cannot help our patients if we
      do not adopt cost-effective interventions.

PMID- 21192265
TI  - Clear lens extraction in angle closure glaucoma.
AB  - PURPOSE OF REVIEW: Clear lens extraction is being advocated for primary angle
      closure disease (PACD). It is important that this advocacy should be based on a
      sound, peer-reviewed evidence base. This review attempts to establish the extent
      of that evidence and provide some management guidelines. RECENT FINDINGS: There
      are only three reports that incorporate clear lens extraction (CLE) for angle
      closure: numbers are sparse and none compare modern phacoemulsification to
      alternative treatments for primary angle closure glaucoma or provide enough
      detail to guide clinical decisions. A Cochrane review in 2006 found that there
      was no evidence to support lens extraction as treatment for primary angle closure
      glaucoma (PACG). More recent randomized controlled trials have provided support
      for cataract extraction--although not specifically for CLE--as treatment for part
      of the spectrum of PACD. A recent review has attempted to provide guidelines for
      application of CLE in PACG by extrapolating from this evidence. SUMMARY: There
      are currently no randomized controlled trials supporting the use of CLE as
      treatment for PACG. A benefit from the procedure is biologically plausible and
      extrapolation from existing randomized trials to a few specific situations may be
      possible. Any potential benefit must be carefully weighed against the risks of
      intervention.

PMID- 21192266
TI  - Management of fecal incontinence after treatment for rectal cancer.
AB  - PURPOSE OF REVIEW: Anorectal dysfunction constitutes a major problem in patients
      surviving rectal cancer. In this review, the current options for management of
      fecal incontinence after treatment for rectal cancer are discussed. RECENT
      FINDINGS: First line therapy should be conservative measures aimed at symptomatic
      control. Dietary regiments, fibers, constipating agents and enemas may be tried.
      Biofeedback is an option to strengthen the external anal sphincter, improve
      rectal sensitivity and coordinate pelvic floor muscles. Colonic irrigation has
      been successful to reduce symptoms and improve quality of life. Surgical
      interventions may be considered if conservative management fails. Sacral nerve
      stimulation is a successful minimal invasive procedure for the treatment of fecal
      incontinence; however, evidence of the method after treatment for rectal cancer
      is still limited. Complex surgical procedures should be limited to only highly
      selected patients. A stoma should be considered when other treatment modalities
      have failed. SUMMARY: Systematic evaluation of the postoperative anorectal
      function in patients treated for rectal cancer should be a standard practice at
      every follow-up. An individually tailored treatment should be offered to the
      severely affected patients to minimize their symptoms. The evidence on the most
      commonly used treatments is sparse, therefore, further randomized controlled
      studies are needed.

PMID- 21192267
TI  - Chemotherapy-induced neuropathic pain.
AB  - PURPOSE OF REVIEW: To discuss the importance, clinical features, possible
      pathology and treatments of chemotherapy-induced neuropathic pain. Newer
      biological agents such as bortezomib will be considered in greater detail. RECENT
      FINDINGS: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent
      complication of common anticancer therapies. It may lead to treatment compromise,
      significantly adds to the symptom burden and interferes with quality of life of
      cancer survivors. Recent investigations have identified processes involved in
      CIPN which may give some insight for the development of novel treatments. CIPN
      induced by different anticancer therapies may be heterogeneous and present as
      distinct neuropathic pains. Recent work has focussed on the newer anticancer
      drugs such as bortezomib. Contemporaneous studies have failed to find good
      evidence for the use of several common antineuropathic agents and further
      research is required. SUMMARY: Painful CIPN remains under recognized and
      undertreated. It is an important cause of pain during cancer treatment and is a
      common pain in the cancer survivor. Difficulties in assessment and limitations in
      treatment contribute to management problems. Improvements in education (patient
      and clinician), assessment and treatment would potentially reduce the often
      debilitating effects of painful CIPN.

PMID- 21192268
TI  - Randomised controlled trial of the effect of oral premedication with
      dexamethasone on hyperglycaemic response to abdominal hysterectomy.
AB  - BACKGROUND: This study was performed to evaluate the metabolic effects of a
      single oral dose of 8 mg dexamethasone in women undergoing hysterectomy. METHODS:
      Ninety non-diabetic women undergoing abdominal hysterectomy were randomised to
      receive 8 mg dexamethasone or placebo 2 h before surgery. Patients' perioperative
      care was standardised (fasting from midnight before surgery, balanced anaesthesia
      using propofol, fentanyl, remifentanil, cisatracurium, desflurane in oxygen/air).
      At five defined time points after drug administration (approximately 2, 4, 6, 10
      and 14 h), blood samples were drawn under fasting conditions to measure blood
      glucose and free (non-esterified) fatty acids (NEFA). Data were analysed using
      analysis of variance for repeated measures. RESULTS: Data of 82 patients
      (dexamethasone: 44 and placebo: 38) were eligible for analysis. There was a
      statistically significant increase in blood glucose in both groups (P = 0.008).
      This increase was more pronounced in patients receiving dexamethasone
      (interaction term: P = 0.02) with maximum values at 6 h after surgery (or
      approximately 10 h after dexamethasone administration). There were 36 patients
      (placebo: 9 = 24% and dexamethasone: 27 = 61%) presenting with elevated glucose
      concentrations (>7 mmol l-1) and 11 patients (placebo: 2 = 5% and dexamethasone:
      9 = 20%) with hyperglycaemia (>8.5 mmol l-1). There were no statistically
      significant changes in the plasma concentrations of NEFA during the perioperative
      period. CONCLUSION: Amounts of dexamethasone frequently used for prophylaxis of
      post-operative nausea and vomiting can cause short-lasting hyperglycaemia in the
      post-operative period, but no relevant alterations in fat metabolism. Thus, the
      benefits of administering corticosteroids should be weighed against the potential
      side-effects of short-lasting hyperglycaemia.

PMID- 21192269
TI  - Risk scores for predicting postoperative nausea and vomiting are clinically
      useful tools and should be used in every patient: con--'life is really simple,
      but we insist on making it complicated'.

PMID- 21192270
TI  - CobraPLUS and Cookgas air-Q versus Fastrach for blind endotracheal intubation: a
      randomised controlled trial.
AB  - BACKGROUND AND OBJECTIVE: CobraPLUS and Cookgas air-Q are supraglottic airways
      expected to allow safe ventilation as well as reliable blind intubation. In a
      prospective, controlled trial, we hypothesised that quality of ventilation and
      success rate of blind endotracheal intubation of these new devices would be
      superior to the Fastrach intubating laryngeal mask airway (ILMA). When blind
      intubation failed the quality of fibrescope-guided intubation was investigated.
      To allow identification of those patients in whom blind intubation would be
      difficult, we investigated the predictive value of currently used predictors for
      ease of endotracheal intubation. METHODS: One hundred and eighty adult patients
      with documented BMI, Mallampati score, Cormack-Lehane classification,
      interincisor gap and thyromental distance were randomised into three groups
      according to the device used. Ventilation conditions were rated as excellent,
      good or difficult. When blind intubation failed, fibrescope-guided intubation
      conditions were rated as well. Statistical analysis was performed by a chi-test.
      RESULTS: The quality of ventilation was excellent for all devices. Three patients
      in the CobraPLUS group and two patients in the ILMA and the Cookgas groups needed
      a slight reposition. Blind intubation through the CPLA was successful in 47%,
      through the Cookgas in 57%, whereas the Fastrach group had a success rate of 95%.
      Fibreoptic intubation was possible in all but one patient. None of the registered
      scores and measures allowed prediction of difficult blind intubation. CONCLUSION:
      All devices appeared to be safe airways. The Fastrach ILMA proved to be a
      reliable facilitator for blind intubation. CobraPLUS and Cookgas air-Q allowed an
      easy fibrescopic intubation. Failed blind intubations could not be predicted by
      the used parameters.

PMID- 21192271
TI  - Two hour glucose post loading: a biomarker of cardiovascular risk in isolated
      clinic hypertension.
AB  - BACKGROUND: Isolated clinic hypertension (ICHT) may be an indicator of both
      future hypertension and diabetes. This study examines the 2-h plasma glucose
      level post load (2hPG), and measures of arterial stiffness, autonomic function
      and circulating biomarkers in ICHT, normotension and hypertension. METHODS:
      Participants aged 39-75 years, who were untreated for hypertension, nonsmokers
      and not known diabetic (n=105) were categorized as normotension, ICHT and
      hypertension, based on clinic and mean daytime ambulatory blood pressures.
      Participants had measurements of autonomic function, aorto-femoral pulse wave
      velocity (PWVc), as well as blood sampling for lipids and potential circulating
      biomarkers [high sensitivity C-reactive protein (hsCRP), plasminogen activator
      inhibitor 1 (PAI-1), asymmetric dimethylarginine (ADMA), and von Willebrand
      factor (vWF)], followed by a glucose tolerance test. RESULTS: A total of 8.3%
      normotension, 37.9% ICHT and 15% hypertension patients had impaired glucose
      tolerance. Mean 2hPG adjusted for age and waist circumference was 5.7 mmol/l
      [interquartile range (IQR) 5.2-6.4] for normotension, 7.4 mmol/l (IQR 6.5-8.3)
      for ICHT (P=0.002 vs. normotension) and 6.2 mmol/l (IQR 5.6-6.9) for hypertension
      group. Other measures of insulin resistance were similar in the three groups.
      Mental stress testing induced a greater blood pressure response in the ICHT group
      (P=0.01 vs. normotension); other autonomic function measures were similar in the
      three groups. Mean PWVc, adjusted for age and blood pressure, was similar in ICHT
      and normotension but increased in the hypertension group. Circulating biomarker
      levels were not different in the three groups. CONCLUSION: Assessment of total
      cardiovascular risk in patients with ICHT should include measurement of
      postprandial glucose.

PMID- 21192272
TI  - Normotension in Lewis and Dahl salt-resistant rats is governed by different
      genes.
AB  - OBJECTIVES: Inbred rodent models simulating essential hypertension and
      normotension are useful tools in discovering genes controlling blood pressure
      (BP) homeostasis. An analysis of a F2 population made from crosses of
      hypertensive Dahl salt-sensitive (DSS) and normotensive Lewis rats did not detect
      a BP quantitative trait locus (QTL) on chromosome 7 (Chr 7). However, false
      negativity could not be excluded. If a BP QTL could be proven to exist, what
      gene(s) may be responsible for this QTL. METHODS: We first constructed reciprocal
      congenic strains for a Chr 7 segment and determined functional domains of
      prominent candidate genes. RESULTS: A congenic strain made in the DSS rat
      background exhibited a BP effect, indicating that a BP QTL, C7QTL, inhabits Chr
      7. Contrarily, a congenic strain constructed in the Lewis rat background did not
      change BP, demonstrating a dependence of C7QTL on the DSS rats environment. Among
      the candidate genes, tachykinin 2 (Tac2), neurexophilin 4 (Nxph4) and retinol
      dehydrogenase 2 (Rdh2) bear nonsynonymous changes comparing DSS and Lewis rats,
      but are the same comparing DSS and Dahl salt-resistant (DSR) rats. In contrast,
      the Lewis alleles of 11-beta-hydroxylase (Cyp11b1), aldosterone synthase
      (Cyp11b2) and Cytochrome P-450 11B3 (Cyp11b3) are identical to those of DSS rats,
      but different from those of DSR rats. CONCLUSION: Thus, the failure to detect a
      linkage between a Chr 7 segment and BP in F2(DSS * Lewis) can be attributed to
      false negativity. Tac2, Nxph4 and Rdh2 are priority candidate genes for C7QTL.
      Lewis and DSR rats are both normotensive, but their underlying genetic
      determinants are different.

PMID- 21192273
TI  - Transcirculation endovascular treatment of complex cerebral aneurysms: technical
      considerations and preliminary results.
AB  - BACKGROUND: Unfavorable anatomy can preclude embolization of intracranial
      aneurysms. Transcirculation techniques, in which a catheter is navigated from one
      side of the brain to the other or from the anterior to the posterior circulation,
      are alternative pathways for primary or balloon- or stent-assisted coiling.
      OBJECTIVE: We report the largest experience in coil embolization of aneurysms
      using transcirculation techniques. METHODS: We reviewed our endovascular database
      from 2006 to 2009 and identified 18 patients who had aneurysms treated with
      transcirculation techniques. RESULTS: Eight patients had anterior and 10 had
      posterior circulation aneurysms. Overall, 8 patients were treated with stent
      assisted coiling and 9 with balloon-assisted coiling, including 1 patient treated
      with a "kissing balloon" technique. Of the 9 patients treated with balloon
      assistance, 1 also was stented at the conclusion of aneurysm coiling. One patient
      with a left fourth vertebral artery (V4) aneurysm was treated with coiling alone
      via a bilateral vertebral artery (VA) approach. In 14 patients, the anterior
      communicating and posterior communicating arteries were used as conduits. In 4
      patients, both VAs were traversed to treat 2 V4 aneurysms and 2 posterior
      inferior cerebellar artery aneurysms. One patient died as a result of treatment
      and was the only permanent complication (5.6%). Complete or near-complete (>95%)
      embolization was achieved in all patients. CONCLUSION: Transcirculation
      techniques are effective pathways for embolization of complex aneurysms. Although
      technically challenging, these techniques are associated with an acceptably low
      rate of complications when compared to the natural history of the treated lesion.

PMID- 21192274
TI  - Autologous bone marrow mononuclear cell therapy for severe traumatic brain injury
      in children.
AB  - BACKGROUND: Severe traumatic brain injury (TBI) in children is associated with
      substantial long-term morbidity and mortality. Currently, there are no successful
      neuroprotective/neuroreparative treatments for TBI. Numerous preclinical studies
      suggest that bone marrow-derived mononuclear cells (BMMNCs), their derivative
      cells (marrow stromal cells), or similar cells (umbilical cord blood cells) offer
      neuroprotection. OBJECTIVE: To determine whether autologous BMMNCs are a safe
      treatment for severe TBI in children. METHODS: Ten children aged 5 to 14 years
      with a postresuscitation Glasgow Coma Scale of 5 to 8 were treated with 6*10
      autologous BMMNCs/kg body weight delivered intravenously within 48 hours after
      TBI. To determine the safety of the procedure, systemic and cerebral hemodynamics
      were monitored during bone marrow harvest; infusion-related toxicity was
      determined by pediatric logistic organ dysfunction (PELOD) scores, hepatic
      enzymes, Murray lung injury scores, and renal function. Conventional magnetic
      resonance imaging (cMRI) data were obtained at 1 and 6 months postinjury, as were
      neuropsychological and functional outcome measures. RESULTS: All patients
      survived. There were no episodes of harvest-related depression of systemic or
      cerebral hemodynamics. There was no detectable infusion-related toxicity as
      determined by PELOD score, hepatic enzymes, Murray lung injury scores, or renal
      function. cMRI imaging comparing gray matter, white matter, and CSF volumes
      showed no reduction from 1 to 6 months postinjury. Dichotomized Glasgow Outcome
      Score at 6 months showed 70% with good outcomes and 30% with moderate to severe
      disability. CONCLUSION: Bone marrow harvest and intravenous mononuclear cell
      infusion as treatment for severe TBI in children is logistically feasible and
      safe.

PMID- 21192276
TI  - Audiometric outcomes for acoustic neuroma patients after single versus multiple
      fraction stereotactic irradiation.
AB  - OBJECTIVE: To compare tumor control and changes in audiometric parameters of
      acoustic neuroma patients treated with either linac-based stereotactic
      radiosurgery (SRS) or stereotactic radiotherapy (SRT) at Allegheny General
      Hospital. STUDY DESIGN: Twenty-three patients with acoustic neuroma were treated
      between February 2003 and April 2009 with either SRS (n = 13) or SRT (n = 10).
      The median age for all patients was 69 years and the median size of lesions was
      1.2 cm (range 0.5-2.2 cm). The prescribed dose was a single dose of 1250 cGy for
      all SRS patients compared to 2500 cGy in 5 daily fractions for SRT patients. All
      patients had pre- and post-procedure audiometry including hearing acuity assessed
      using pure tone average (PTA), speech discrimination score (SDS), and speech
      reception threshold (SR). The results of treatment type and tumor variables
      resulting in hearing degradation were evaluated and compared. RESULTS: At a
      median follow-up of 13 months (range 3-36 months), only 1 of 13 patients treated
      with SRS and 2 of 10 patients treated with SRT develped progression of disease.
      However; all patients developed deterioration in PTA, SDS, or SR on the treated
      side. There were no statistically significant audiometric differences between
      patients treated with SRT or SRS and tumor response was similar regardless of
      irradiation technique. CONCLUSION: Both SRS and SRT provide excellent local
      control rates for the treatment of acoustic neuroma. While SRS demonstrated a
      trend toward worsening of SDS and the treatment of lesions >1.2 cm demonstrated a
      trend toward worsening of PTA, neither reached statistical significance. Our data
      suggest that single dose irradiation using the SRS technique should be considered
      primarily for patient convenience. All patients treated with radiotherapy for
      acoustic neuromas should undergo formal hearing testing before and after
      treatment.

PMID- 21192277
TI  - Activation of serotonergic neurons during salicylate-induced tinnitus.
AB  - HYPOTHESIS: Serotonergic neurons are activated during salicylate-induced tinnitus
      and modulate the cochlea during tinnitus. BACKGROUND: During salicylate-induced
      tinnitus in the gerbil, neurons in the dorsal raphe nucleus were activated.
      Because approximately half of the neurons in this region are serotonergic, this
      indicates that serotonin (5-HT) might play a role in the mechanisms of central
      tinnitus. The goal of this study was to determine if serotonergic neurons are
      activated during salicylate-induced tinnitus. Furthermore, to determine if the
      same neurons might modulate the cochlea during tinnitus, neuroanatomic tract
      tracing with 5-HT immunohistochemistry was used to determine if serotonergic
      neurons project to the gerbil cochlea. METHODS: A randomized, prospective study
      was performed. Six gerbils were injected with salicylate (saline for controls).
      Four hours later, the gerbils were euthanized and perfused, and their brains were
      collected for immunohistochemical labeling of 5-HT and c-fos. For the tract
      tracing, FluoroGold was injected into the cochleae of 3 gerbils. The gerbils were
      euthanized and perfused 4 to 11 days later, and the brains immunohistochemically
      were processed for 5-HT. RESULTS: More serotonergic neurons expressed c-fos in
      the salicylate-injected animals compared with the controls. The increase was
      significant for 3 of the 8 major serotonergic cell groups including B7, B9, and
      the caudal linear nucleus. Despite robust labeling of olivocochlear and
      vestibular efferents with FluoroGold, 5-HT-labeled neurons containing FluoroGold
      were lacking. CONCLUSION: Salicylate-induced tinnitus activates serotonergic
      neurons in rostral cell groups. Activation of these neurons is not likely to
      influence cochlear function directly but is likely to influence a number of
      auditory and nonauditory regions known to be involved with tinnitus.

PMID- 21192278
TI  - Role of estrogen receptor-dependent upregulation of P38 MAPK/heme oxygenase 1 in
      resveratrol-mediated attenuation of intestinal injury after trauma-hemorrhage.
AB  - Resveratrol protects against organ injury caused by trauma-hemorrhage, although
      the mechanism remains unknown. We have previously shown that it exerts protective
      effects in the liver via estrogen receptors and their signaling. Thus, we set out
      to determine whether resveratrol-mediated estrogen receptor-dependent p38 mitogen
      activated protein kinase (MAPK)/heme oxygenase 1 activation protects the
      intestine after trauma-hemorrhage. To study this, male Sprague-Dawley rats
      underwent trauma-hemorrhage (mean blood pressure, ~ 40 mmHg for 90 min) followed
      by fluid resuscitation. Animals were pretreated with an estrogen receptor
      antagonist (ICI 182,780), a specific p38 MAPK inhibitor (SB-203580), or a heme
      oxygenase enzyme antagonist (chromium-mesoporphyrin) 30 min before vehicle or
      resveratrol (30 mg/kg) administration, followed by resuscitation, and were killed
      2 h thereafter. Intestinal water content, myeloperoxidase activity, and TNF
      alpha, IL-6, intercellular adhesion molecule 1, cytokine-induced neutrophil
      chemoattractant (CINC) 1, and CINC-3 levels and edema of the lung were measured.
      Mean arterial blood pressure, cardiac output, positive maximal pressure of left
      ventricular increase (+dP/dtmax), and negative maximal pressure of left
      ventricular decrease (-dP/dtmax) were also determined. Intestinal p38 MAPK
      activity and heme oxygenase 1 expression were also determined. Trauma-hemorrhage
      led to an increase in intestinal water content, myeloperoxidase activity, and TNF
      alpha, IL-6, intercellular adhesion molecule 1, CINC-1, and CINC-3 levels. This
      was accompanied by a decrease in intestinal p38 MAPK activity. Administration of
      resveratrol improved all of the above parameters. Resveratrol treatment also
      increased intestinal heme oxygenase 1 expression as compared with vehicle-treated
      trauma-hemorrhaged rats. Administration of ICI 182,780, SB-203850, or chromium
      mesoporphyrin with resveratrol abolished the resveratrol-mediated improvement of
      the above parameters. Resveratrol administration also attenuated trauma
      hemorrhage-induced cardiac dysfunction and edema of the lung. These results
      suggest that estrogen receptor-dependent upregulation of the p38 MAPK/heme
      oxygenase 1 pathway plays a critical role in mediating the salutary effects of
      resveratrol on shock-induced intestinal injury.

PMID- 21192279
TI  - Thenar oxygen saturation and invasive oxygen delivery measurements in critically
      ill patients in early septic shock.
AB  - This prospective study was aimed to test the hypothesis that tissue hemoglobin
      oxygen saturation (StO2) measured noninvasively using near-infrared spectroscopy
      is a reliable indicator of global oxygen delivery (DO2) measured invasively using
      a pulmonary artery catheter (PAC) in patients with septic shock. The study
      setting was a 26-bed medical-surgical intensive care unit at a university
      hospital. Subjects were adult patients in septic shock who required PAC
      hemodynamic monitoring for resuscitation. Interventions included transient
      ischemic challenge on the forearm. After blood pressure normalization,
      hemodynamic and oximetric PAC variables and, simultaneously, steady-state StO2
      and its changes from ischemic challenge (deoxygenation and reoxygenation rates)
      were measured. Fifteen patients were studied. All the patients had a mean
      arterial pressure above 65 mmHg. The DO2 index (iDO2) range in the studied
      population was 215 to 674 mL O2/min per m. The mean mixed venous oxygen
      saturation value was 61% +/- 10%, mean cardiac index was 3.4 +/- 0.9 L/min per m,
      and blood lactate level was 4.6 +/- 2.7 mmol/L. Steady-state StO2 significantly
      correlated with iDO2, arterial and venous O2 content, and O2 extraction ratio. A
      StO2 cutoff value of 75% predicted iDO2 below 450, with a sensitivity of 0.9 and
      a specificity of 0.9. In patients in septic shock and normalized MAP, low StO2
      reflects extremely low iDO2. Steady-state StO2 does not correlate with moderately
      low iDO2, indicating poor sensitivity of StO2 to rule out hypoperfusion.

PMID- 21192280
TI  - The heat shock paradox and cardiac myocytes: role of heat shock factor.
AB  - The induction of the heat shock (HS) response is accepted to be a protective
      response, reducing injury and improving cell survival. However, when inflammation
      precedes HS, there is an unexpected increase in injury, known as the HS paradox,
      which is hypothesized to be a mechanism underlying multiorgan dysfunction. We
      hypothesized that the HS paradox would occur in adult cardiac myocytes and that
      HS factor (HSF) 1 would contribute to injury. Heat shock at 42 degrees C and TNF
      (10 ng/mL) were used as the HS and the inflammatory insult, respectively. The
      combination of TNF followed by HS (TNF/HS) caused the greatest amount of
      apoptosis in adult rat cardiac myocytes. TNF/HS resulted in an increase in HS
      protein (HSP) 60, compared with untreated cells, those receiving HS/TNF, or TNF
      alone. There was no increase in heme oxygenase 1 in any of the groups. Heat shock
      protein 72 increased in all the groups, with the greatest levels with TNF/HS.
      Nuclear factor kappaB activation was greatest with TNF/HS. Pretreatment with a
      DNA-binding decoy for HSF-1 prevented the increase in HSPs and decreased
      apoptosis in all groups. However, the increase in iNOS, seen in all treatment
      groups, was unaffected by the HSF-1-binding decoy. We conclude that the HS
      paradox occurs in adult cardiac myocytes, that HSP60 is increased as part of the
      HS paradox, and that HSF-1 activation contributes to injury.

PMID- 21192281
TI  - Measure for measure-determination of infarct size in murine models of myocardial
      ischemia and reperfusion: a systematic review.
AB  - Myocardial ischemia/reperfusion injury (MI/R) is one of the most prominent topics
      of contemporary research. The frequent failure of potential therapeutic drugs and
      interventions to transfer to clinical practice demonstrates the limitations in
      using experimental animal models. Because a variety of transgenic animals are
      readily available in mice, researchers in recent years have made use of murine
      models rather than of larger animal models for experimental MI/R. This review
      focuses on in vivo and ex vivo murine models of MI/R and aims to characterize the
      source of our mechanistic understanding in mice. A systematic review of the
      literature demonstrated that there is great diversity among ex vivo (Langendorff)
      and in vivo models of MI/R.

PMID- 21192282
TI  - Transfusion-related risk of secondary bacterial infections in sepsis patients: a
      retrospective cohort study.
AB  - There is a need for insight into factors that contribute to late mortality of
      sepsis patients. Immunomodulatory effects have been ascribed to blood
      transfusion. This retrospective cohort study investigates the association between
      the development of nosocomial bacterial infection and transfusion of
      leukodepleted red blood cells (RBCs) or platelets (PLTs) in survivors of the
      initial phase of sepsis. Patients diagnosed with sepsis after admission to the
      intensive care unit of a tertiary referral hospital were included. Of 134
      patients with sepsis, 67 received a blood transfusion (50%). A secondary
      infection developed in 19 patients (14%). A multiple logistic regression model
      revealed that the use of immunosuppressive medication with an odds ratio (OR) of
      1.17 (95% confidence interval [CI], 1.04-1.31), but not Acute Physiology and
      Chronic Health Evaluation II score, malignancy, HIV infection, alcohol abuse, or
      diabetes mellitus, was a risk factor for nosocomial infection. In an adjusted
      model, the amount of transfused RBCs was associated with secondary infection with
      an OR of 1.18 (95% CI, 1.01-1.37). Storage time of RBCs was a relevant confounder
      of the effect of the amount of RBCs on infection, with an adjusted OR of 1.25
      (95% CI, 1.04-1.51), P = 0.02. Also, the amount of transfused PLTs was associated
      with secondary infection, with an OR of 1.36 (95% CI, 1.05-1.78). In conclusion,
      transfusion of RBCs and PLTs is associated with the onset of secondary bacterial
      infection in sepsis patients. Storage time of RBCs influences this increased
      risk. These findings suggest that immunomodulatory effects of blood transfusion
      contribute to adverse outcome in the convalescent phase of sepsis.

PMID- 21192283
TI  - Midkine, a multifunctional cytokine, in patients with severe sepsis and septic
      shock: a pilot study.
AB  - The objective of the study was to evaluate whether severe sepsis and septic shock
      are related to alterations in midkine concentrations, to identify disease-related
      factors associated with these alterations, and to initially appraise whether
      midkine might serve as a biomarker in sepsis. Prospective observational cross
      sectional study with 5-day follow-up. Circulating midkine was measured (enzyme
      linked immunosorbent assay) in 38 septic (13 with severe sepsis, 25 with septic
      shock), 82 active inflammatory bowel disease (IBD) (26 with systemic inflammatory
      response syndrome [SIRS]) patients, and 87 healthy subjects. Midkine
      significantly increased along with a sequence: health-inflammation (IBD)-systemic
      inflammation (IBD-SIRS)-severe sepsis/septic shock. High midkine levels (>1,000
      ng/L) were found in 63% of septic and in 19% of IBD-SIRS patients, whereas
      extremely high concentrations (>5,000 ng/L) were found in 16% vs. 4%. Although
      not different at admission, midkine gradually decreased in severe sepsis and
      remained high in shock. Similarly, persistently high midkine was observed in
      patients with cardiovascular insufficiency (CVI) and in mechanically ventilated
      as compared with normalizing levels in patients without CVI and not requiring
      ventilation. The differences in devised simple rates (Delta5th-1st) were
      significant in all these cases. Accordingly, admission midkine was higher in
      patients with metabolic acidosis. Concerning pathogen, gram-positive infections
      were associated with the highest midkine levels. In conclusion, sepsis and septic
      shock are associated with midkine elevation, substantially more pronounced than
      in inflammation, even systemic, revealing a new potential mediator of
      deregulation of neutrophil migration. Sepsis-related global hypoxia seems to
      contribute to midkine elevation. Our results substantiate further research on
      possible midkine application as a sepsis biomarker: in differentiating SIRS from
      sepsis and identifying gram-positive sepsis and septic patients at risk of CVI
      and shock.

PMID- 21192284
TI  - Adenosine negative feedback on A2A adenosine receptors mediates
      hyporesponsiveness in chronically septic mice.
AB  - Strategies are needed to reverse the immune cell hyporesponsiveness and prevent
      bacterial overgrowth associated with high mortality rates in septic patients.
      Adenosine signaling may be mediating immunosuppressive signals within the
      inflammatory microenvironment that are safeguarding bacteria by rendering immune
      cells hyporesponsive. We examined A2A adenosine receptor (A2AR)-mediated immune
      responses in a chronic model of cecal ligation and puncture (CLP)-induced sepsis
      using both wild-type (WT) and A2AR knockout (KO) mice. In this model, chronic
      bacterial peritonitis was established that results in the first death on day 4.
      A2A adenosine receptors promoted bacterial overgrowth that was associated with a
      high 28-day sepsis mortality (WT 87% vs. A2AR KO 13%; P < 0.0001). Chronic
      bacteremia persisted in both WT and A2AR KO mice over the 28-day study period.
      Bacteremia was significantly decreased in A2AR KO mice 2 days after antibiotic
      therapy cessation (day 6 after CLP; P < 0.005). Local and disseminated bacteria
      levels were compared at the end of the 28-day study period or from moribund mice.
      A2A adenosine receptor deficiency dramatically decreased peritoneal (P < 0.05),
      splenic (P < 0.05), and blood (P < 0.01) bacterial levels. A2A adenosine receptor
      deficiency caused an early reduction in inflammatory mediators IL-6, macrophage
      inflammatory protein 2, TNF-srI, and TNF-srII (P < 0.05), but not in TNF-alpha,
      IL-1beta, IL-10, or monocyte chemotactic protein 1 within 24 h after CLP. In
      response to an intravenous lipopolysaccharide (day 5 after CLP) challenge, A2AR
      KO mice showed enhanced secretion of TNF-alpha (2 h), IFN-gamma, IL-6, monocyte
      chemotactic protein 1, IL-10, and macrophage inflammatory protein 2 (9 h) (P <
      0.05), suggesting that A2ARs attenuate inflammatory responses to repeat
      infectious insults. These data demonstrate that A2AR blockade may be an effective
      immunotherapy treatment to prevent bacterial overgrowth and reduce mortality
      secondary to immunosuppression in septic patients.

PMID- 21192285
TI  - Proteomic analysis of human mesenteric lymph.
AB  - Extensive animal work has established mesenteric lymph as the mechanistic link
      between gut ischemia/reperfusion and distant organ injury. Our trauma and
      transplant services provide a unique opportunity to assess the relevance of our
      animal data to human mesenteric lymph under conditions that simulate those used
      in the laboratory. Mesenteric lymph was collected from 11 patients with lymphatic
      injuries, during semielective spine reconstruction or immediately before organ
      donation. The lymph was tested for its ability to activate human neutrophils in
      vitro and was analyzed by label-free proteomic analysis. Human mesenteric lymph
      primed human polymorphonuclear neutrophils in a pattern similar to that observed
      in previous rodent, swine, and primate studies. A total of 477 proteins were
      identified from the 11 subjects' lymph samples with greater than 99% confidence.
      In addition to classic serum proteins, markers of hemolysis, extracellular matrix
      components, and general tissue damage were identified. Both tissue injury and
      shock correlate strongly with production of bioactive lymph. Products of red
      blood cell hemolysis correlate strongly with human lymph bioactivity, and
      immunoglobulins have a negative correlation with the proinflammatory lymph. These
      human data corroborate the current body of research implicating postshock
      mesenteric lymph in the development of systemic inflammation and multiple organ
      failure. Further studies will be required to determine if the proteins identified
      participate in the pathogenesis of multiple organ failure and if they can be used
      as diagnostic markers.

PMID- 21192286
TI  - Development of a short form of the Orebro Musculoskeletal Pain Screening
      Questionnaire.
AB  - STUDY DESIGN: A longitudinal design where the questionnaire was completed at a
      pretest and predictive ability evaluated with a 1-year follow-up. A second sample
      was employed to provide a replication. OBJECTIVE: The aim of the study was to
      validate a short form of the Orebro Musculoskeletal Pain Screening Questionnaire
      (OMSPQ). SUMMARY OF BACKGROUND DATA: Several studies demonstrate the research and
      clinical utility of the OMSPQ. Calls have been made for a shorter form that
      requires less time in administering. METHODS: The short version was constructed
      by taking two items from each of the five factors shown to have predictive power.
      It was then tested against the long form in two samples of people with
      musculoskeletal pain where one reflects an occupational health care population (N
      = 324) and the other a primary care population (N = 183) thus providing a built
      in replication. All participants completed the OMSPQ and were then followed over
      the course of a year to evaluate disability as measured by sick leave. RESULTS:
      The correlation between the short and long forms was 0.91. The receiver operating
      characteristic curve was nearly identical for the long and short versions of the
      questionnaire (e.g., primary care sample: 0.84 vs. 0.81; occupational sample:
      0.72 vs. 0.70). Of those who developed disability, a cutoff of 50 on the short
      version identified 85% in the occupational and 83% in the primary care samples
      which was nearly as good as the full version. CONCLUSION: The short form of the
      OMSPQ is appropriate for clinical and research purposes, since it is nearly as
      accurate as the longer version.

PMID- 21192287
TI  - Altered blood flow distribution in the rat spinal cord under chronic compression.
AB  - STUDY DESIGN: Sham-operation-controlled animal study to assess alterations in
      blood flow in the spinal cord in a chronic compression model. Laboratory
      investigation. OBJECTIVE: Cervical myelopathy is a common cause of disability in
      elderly patients. Hypothesis was made that ischemia subsequent to the spinal cord
      compression plays an important role in the pathogenesis of the spinal cord
      dysfunction. This study was undertaken to assess alterations in the blood flow of
      the spinal cord under chronic compression in a rat model. SUMMARY OF BACKGROUND
      DATA: Histologic study of spinal cord from patients with spondylotic myelopathy
      showed ischemic tissue changes. Experimentally, spinal cord hypoperfusion in
      combination with chronic spinal cord compression induced myelopathy in dogs. We
      previously showed that chronic compression of the spinal cord in rats produces
      gradual deterioration of mobility of the animals accompanied by cord tissue
      degeneration compatible with ischemic changes. METHODS: Chronic compression of
      the cervical spinal cord was implemented by implantation of a thin urethane
      polymer sheet under the C5-C6 laminae, which expands by absorbing tissue water
      over 48-72 hours. The control group underwent sham operation. Twelve weeks later,
      blood flow to the C3-C4 and C5-C6 spinal cord segments were measured by
      fluorescent microsphere methods. RESULTS: In the control group, the blood flow in
      the C5-C6 segment was larger than C3-C4 segment. In the compression group, the
      blood flow in the C5-C6 was significantly reduced compared to the C3-C4 segment.
      CONCLUSION: Under chronic focal spinal cord compression, there was a decrease of
      the blood flow in the compressed segment in comparison to the rostral segment.
      Our data are compatible with the hypothesis that alteration in the spinal cord
      blood flow contributes to pathogenesis of myelopathy.

PMID- 21192288
TI  - Rates of infection after spine surgery based on 108,419 procedures: a report from
      the Scoliosis Research Society Morbidity and Mortality Committee.
AB  - STUDY DESIGN: Retrospective review of a prospectively collected database.
      OBJECTIVE: Our objective was to assess the rates of postoperative wound infection
      associated with spine surgery. SUMMARY OF BACKGROUND DATA: Although wound
      infection after spine surgery remains a common source of morbidity, estimates of
      its rates of occurrence remain relatively limited. The Scoliosis Research Society
      prospectively collects morbidity and mortality data from its members, including
      the occurrence of wound infection. METHODS: The Scoliosis Research Society
      morbidity and mortality database was queried for all reported spine surgery cases
      from 2004 to 2007. Cases were stratified based on factors including diagnosis,
      adult (>= 21 years) versus pediatric (<21 years), primary versus revision, use of
      implants, and whether a minimally invasive approach was used. Superficial, deep,
      and total infection rates were calculated. RESULTS.: In total, 108,419 cases were
      identified, with an overall total infection rate of 2.1% (superficial = 0.8%,
      deep = 1.3%). Based on primary diagnosis, total postoperative wound infection
      rate for adults ranged from 1.4% for degenerative disease to 4.2% for kyphosis.
      Postoperative wound infection rates for pediatric patients ranged from 0.9% for
      degenerative disease to 5.4% for kyphosis. Rate of infection was further
      stratified based on subtype of degenerative disease, type of scoliosis, and type
      of kyphosis for both adult and pediatric patients. Factors associated with
      increased rate of infection included revision surgery (P < 0.001), performance of
      spinal fusion (P < 0.001), and use of implants (P < 0.001). Compared with a
      traditional open approach, use of a minimally invasive approach was associated
      with a lower rate of infection for lumbar discectomy (0.4% vs. 1.1%; P < 0.001)
      and for transforaminal lumbar interbody fusion (1.3% vs. 2.9%; P = 0.005).
      CONCLUSION: Our data suggest that postsurgical infection, even among skilled
      spine surgeons, is an inherent potential complication. These data provide general
      benchmarks of infection rates as a basis for ongoing efforts to improve safety of
      care.

PMID- 21192289
TI  - Short-term morbidity and mortality associated with correction of thoracolumbar
      fixed sagittal plane deformity: a report from the Scoliosis Research Society
      Morbidity and Mortality Committee.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: Our objective was to assess the
      short-term complication rate in patients undergoing treatment of thoracolumbar
      fixed sagittal plane deformity (FSPD). SUMMARY OF BACKGROUND DATA: The reported
      morbidity and mortality for the surgical treatment of thoracolumbar FSPD is
      varied and based on studies with small sample sizes. Further studies are needed
      to better assess FSPD complication rate, and the factors that influence it.
      METHODS: The Scoliosis Research Society (SRS) Morbidity and Mortality Database
      was queried to identify cases of thoracolumbar FSPD from 2004 to 2007.
      Complications were analyzed based on correction technique, surgical approach,
      surgeon experience (SRS membership status used as a surrogate), patient age, and
      history of prior surgery. RESULTS: Five hundred and seventy-eight cases of FSPD
      were identified. Osteotomies were performed in 402 cases (70%), including 215
      pedicle subtraction osteotomies (PSO), 135 Smith-Petersen osteotomies (SPO), 19
      anterior discectomy with corpectomy procedures (ADC), 18 vertebral column
      resections (VCR), and 15 unspecified osteotomies. There were 170 complications
      (29.4%) in 132 patients. There were three deaths (0.5%). The most common
      complications were durotomy (5.9%), wound infection (3.8%), new neurologic
      deficit (3.8%), implant failure (1.7%), wound hematoma (1.6%), epidural hematoma
      (1.4%), and pulmonary embolism (1.0%). Procedures including an osteotomy had a
      higher complication rate (34.8%) than cases not including an osteotomy (17.0%, P
      < 0.001), and this remained significant after adjusting for the effects of
      patient age, surgeon experience, and history of prior surgery (P = 0.003, odds
      ratio = 2.070, 95% CI = 1.291-3.321). Not significantly associated with
      complication rate were patient age (P = 0.68), surgeon experience (P = 0.18), and
      history of prior surgery (P = 0.10). Complication rates were progressively higher
      from no osteotomy (17.0%), to SPO (28.1%), to PSO (39.1%), to VCR (61.1%).
      CONCLUSION: The short-term complication rate for treatment of FSPD is 29.4%. The
      complication rate was significantly higher in patients undergoing osteotomies,
      and more aggressive osteotomies were associated with progressively higher
      complication rates.

PMID- 21192290
TI  - Differences in the relationship between psychosocial distress and self-reported
      disability in patients with chronic low back pain in six pain rehabilitation
      centers in the Netherlands.
AB  - STUDY DESIGN: A cross sectional multicenter study in six outpatient
      Rehabilitation Centers (RCs) in the Netherlands. OBJECTIVE: This study aims to
      confirm or refute the finding that a strong relationship exists between
      psychosocial distress and self-reported disability in patients with nonspecific
      chronic low back pain (CLBP) by analyzing this relationship in patients with CLBP
      admitted for treatment in six RCs. SUMMARY OF BACKGROUND DATA: A strong
      relationship between psychosocial distress and self-reported disability in
      patients with CLBP is suggested. However, in former research weak relationships
      were found in two of the RCs participating in this study. METHODS: Total study
      sample consisted of 293 patients (30-66 per RC) with CLBP, admitted for
      outpatient multidisciplinary rehabilitation in one of the six participating RCs.
      Psychosocial distress was measured with the Symptom Checklist-90-Revised (SCL-90
      R), self-reported disability with the Roland Morris Disability Questionnaire
      (RMDQ). Pearson correlation coefficients between psychosocial distress and self
      reported disability were calculated. Multivariate regression analysis was
      performed to analyze the relationship between SCL-90-R and VAS pain (independent
      variables) and RMDQ (dependent variable) for the total group and for each RC
      separately. A multivariate regression analysis was performed to analyze the
      relationship between all baseline characteristics and RMDQ in the total group.
      RESULTS: Correlation coefficient between the SCL-90-R and RMDQ was r = 0.38 for
      the total sample, indicating a significant (P < 0.05), but weak relationship. For
      the six individual RCs, correlation coefficients ranged between r = 0.22 and 0.67
      (three of the six correlation coefficients were significant). The explained
      variance (r) of the regression models (SCL-90 and pain intensity as predictors of
      RMDQ) was 29% for the total sample, and varied between the RCs from 17% to 52%.
      Results of the multivariate regression analysis of all baseline characteristics
      of the total group revealed that the model explained 36% of the total variance
      observed in RMDQ score. Overall, the contributions of psychosocial distress to
      the models were smaller and more variable compared with pain intensity.
      CONCLUSION: The overall relationship between psychosocial distress and self
      reported disability was weak, and differences between RCs were considerable. This
      indicates that the relationship between psychosocial distress and disability in
      patients with CLBP is not uniform.

PMID- 21192291
TI  - Limaprost alfadex, a prostaglandin E1 derivative, prevents deterioration of
      forced exercise capability in rats with chronic compression of the spinal cord.
AB  - STUDY DESIGN: Basic animal research. OBJECTIVE: Cervical spondylotic myelopathy
      is a common condition among elderly and often treated by surgery. To explore
      possibility of pharmacologic treatment, limaprost alfadex, a prostaglandin E1
      derivative with vasodilatory and antiplatelet action, was tried in a rat chronic
      spinal cord compression model. SUMMARY OF BACKGROUND DATA: Limaprost increased
      the blood flow of cauda equina and improved motor functions in animal models of
      lumbar stenosis. The drug is clinically used to treat neurogenic intermittent
      claudication. METHODS: : Forty-two rats were allocated to four groups: (A) sham
      operation without permanent cord compression, given 5 mL/kg of distilled water
      twice a day (n = 6); (B) sham operation, receiving 300 MUg/kg limaprost twice a
      day (n = 6); (C) cord compression, receiving the vehicle (n = 15); and (D) cord
      compression receiving the drug (n = 15). A thin polyurethane sheet that expands
      by absorbing water was implanted under the C5-C6 laminae to produce cord
      compression. For sham operation, the sheet was immediately removed. Exercise
      tests were repeated on a rotating treadmill until 26 weeks after surgery, and
      then the animals were killed and the spinal cord harvested for motor neurons
      counts. RESULTS.: Treadmill endurance (seconds, mean +/- standard error of mean)
      2 weeks after surgery was 497.7 +/- 2.3, 434.5 +/- 65.5, 423.1 +/- 33.0, and
      480.5 +/- 19.5 in groups A, B, C, and D, respectively. At 26th week, the duration
      was 497.7 +/- 2.3, 421.2 +/- 78.8, 21.3 +/- 11.7, and 441.3 +/- 40.4 (P < 0.0001
      for the decrease in C group, multivariate analysis of variance with correction
      for multiple measures.) The motor neuron counts were 38.3 +/- 3.6, 38.2 +/- 2.6,
      32.6 +/- 1.9, and 36.2 +/- 2.3 in groups A, B, C, and D (P = 0.34), respectively.
      CONCLUSION: Limaprost alfadex prevented decline of forced locomotion capability
      in rats with chronic compression of the cervical cord.

PMID- 21192292
TI  - Local application of interleukin-6 to the dorsal root ganglion induces tumor
      necrosis factor-alpha in the dorsal root ganglion and results in apoptosis of the
      dorsal root ganglion cells.
AB  - STUDY DESIGN: The mechanisms of apoptosis behind the formation of tissue
      reactions at the surface of the dorsal root ganglion (DRG) exposed to the nucleus
      pulposus were studied with special reference to the role of interleukin-6 (IL-6),
      using electron microscopy and immunohistochemistry in rats. OBJECTIVE: To study
      the role of IL-6 on the DRG. SUMMARY OF BACKGROUND DATA: It has been reported
      that nucleus pulposus cells are capable to produce proinflammatory cytokines,
      including tumor necrosis factor-alpha (TNF-alpha) and IL-6. Recently, it was
      observed that local application of nucleus pulposus induced a characteristic
      tissue reaction at the surface of the DRG. This change was due to apoptosis of
      DRG neurons. However, the role of IL-6 is not known regarding the apoptosis of
      the DRG neurons. METHODS: Recombinant IL-6 was applied between the L4 DRG and the
      dura to mimic a disc herniation of the L4-L5 disc in rats. The L4 DRGs were
      resected 24 hours after surgery. The sections were processed for
      immunohistochemistry using antisera to TNF-alpha. Furthermore, the sections of
      the specimens were observed using light and electron microscopy to confirm the
      induced apoptosis of the DRG neurons. The sections were also processed for
      immunohistochemistry, using antisera to single-stranded DNA (ssDNA) and Caspase
      3. RESULTS: TNF-alpha immunoreactivity was observed in the peripheral area of DRG
      at the site of the application of IL-6. Typical changes of the cell nuclei were
      observed in the DRG by light and electron microscopy, indicating the presence of
      apoptosis. The presence of ssDNA and Caspase 3 further enhanced the impression
      that there was apoptosis of the DRG neurons. CONCLUSION: IL-6 seemed to induce
      TNF-alpha at the surface of DRG exposed to IL-6 and to induce a characteristic
      reaction at the surface of the DRG. IL-6 may thus play an important role in
      nucleus pulposus-induced apoptosis of the DRG neurons as well as TNF-alpha.

PMID- 21192293
TI  - Neural stem cells modified by a hypoxia-inducible VEGF gene expression system
      improve cell viability under hypoxic conditions and spinal cord injury.
AB  - STUDY DESIGN: An in vitro neural hypoxia model and rat spinal cord injury (SCI)
      model were used to assess the regulation of therapeutic vascular endothelial
      growth factor (VEGF) gene expression in mouse neural stem cells (mNSCs) by the
      EPO (erythropoietin) enhancer or RTP801 promoter. OBJECTIVE: To increase VEGF
      gene expression in mNSCs under hypoxic conditions in SCI lesions but avoid
      unwanted overexpression of VEGF in normal sites, we developed a hypoxia-inducible
      gene expression system consisting of the EPO enhancer and RTP801 promoter fused
      to VEGF or the luciferase gene, then transfected into mNSCs. SUMMARY OF
      BACKGROUND DATA: On the basis of the ischemic response in the injured area, poor
      cell survival at the transplantation site is a consistent problem with NSC
      transplantation after SCI. Although VEGF directly protects neurons and enhances
      neurite outgrowth, uncontrolled overexpression of VEGF in uninjured tissue may
      cause serious adverse effects. To effectively improve NSC survival in ischemic
      sites after transplantation, we evaluated mNSCs modified by a hypoxia-inducible
      VEGF gene expression system in an SCI model. METHODS: Hypoxia-inducible
      luciferase or VEGF plasmids were constructed using the EPO enhancer or RTP801
      promoter. The effect of these systems on targeted gene expression and cell
      viability was evaluated in mNSCs in both hypoxic in vitro injury and a rat SCI
      model in vivo. RESULTS: The gene expression system containing the EPO enhancer or
      RTP801 promoter significantly increased the expression of the luciferase reporter
      gene and therapeutic VEGF gene under hypoxic conditions. The Epo-SV-VEGF plasmid
      transfection group had significantly fewer apoptotic cells in vitro. This system
      also augmented cell viability in the in vivo SCI model. CONCLUSION: These results
      strongly suggest the potential utility of mNSCs modified by a hypoxia-inducible
      VEGF gene expression system in the development of effective stem cell
      transplantation protocols in SCI.

PMID- 21192294
TI  - A novel approach to quantitatively assess posttraumatic cervical spinal canal
      compromise and spinal cord compression: a multicenter responsiveness study.
AB  - STUDY DESIGN: Multicenter retrospective study. OBJECTIVE: To examine whether
      posttraumatic cervical spinal canal compromise and spinal cord compression are
      responsive to changes in motor and sensory functions. SUMMARY OF BACKGROUND DATA:
      The maximum canal compromise (MCC) and maximum spinal cord compression (MSCC)
      were developed to quantitatively assess canal stenosis and spinal cord
      compression using computed tomographic (CT) scan and magnetic resonance imaging
      (MRI) in the setting of acute spine trauma. METHODS: We included 100 consecutive
      patients with acute spine trauma. Patients were classified into three groups as
      follows: patients with acute spine trauma without spinal cord injury (group 1),
      patients with incomplete spinal cord injury (group 2), and patients with complete
      spinal cord injury (group 3). We studied three quantitative imaging parameters
      given as follows: MCC using CT-based measurements, MCC using T1-MRI based
      measurements, and MSCC using T2-MRI based measurements. RESULTS: There were 78
      male patients and 22 female patients with ages from 17 to 82 years (mean age = 45
      years). In group 1, there were no significant differences regarding the mean MRI
      MCC and MSCC among the spine levels. Although most spine levels were
      statistically comparable regarding the CT-MCC in patients of group 1, the C7
      level significantly differed from the C3 level. Comparisons among all three
      patient groups showed significant differences regarding the mean MRI-MCC and
      MSCC, but no significant differences were observed in the mean CT-MCC between
      groups 1 and 2, and between groups 1 and 3. Data analyses using operating
      characteristics of each radiologic parameter indicated that only the MRI
      parameters had consistently optimal cutoff points to distinguish between groups 1
      and 2, and between groups 2 and 3. CONCLUSION: Our results suggest that the MRI
      based measurements of canal compromise and spinal cord compression are responsive
      to changes in motor and sensory functions. However, the MCC using CT-based
      measurements provides inconsistent results that can result in misdiagnosis in the
      clinical setting.

PMID- 21192295
TI  - High heritability for concurrent low back and neck-shoulder pain: a study of
      twins.
AB  - STUDY DESIGN: A cross-sectional study on 21,225 twins based on a Web-based
      questionnaire was performed in 2005-2006 and administered by the Swedish Twin
      Registry. OBJECTIVE: To investigate the importance of genetic factors for the
      occurrence of "Concurrent low back (LBP) and neck-shoulder pain (NSP)" as well as
      of "Solely LBP," and "Solely NSP" in an adult population of women and men.
      SUMMARY OF BACKGROUND DATA: Many individuals suffering from LBP also have
      concurrent NSP, and little is known about the factors influencing the occurrence
      of this spinal comorbidity. METHODS: Heritability of Concurrent LBP and NSP,
      solely LBP, and solely NSP was analyzed in 2934 monozygotic twin pairs, 2009 same
      sex dizygotic (DZ) twin pairs, and 1960 opposite-sex DZ twin pairs without any
      known rheumatic disorders using structural equation modeling (SEM). RESULTS: The
      SEM showed that 60% of the total variance for concurrent LBP and NSP can be
      explained by additive genetic effects, which was twice as large as for solely LBP
      (30%) and more than twice as large as for solely NSP (24%). CONCLUSION: Genetic
      factors had a considerably greater importance for the occurrence of concurrent
      LBP and NSP compared with solely LBP or solely NSP. The influence of genetic
      factors was similar for solely LBP and solely NSP.

PMID- 21192296
TI  - The effects of therapeutic climbing in patients with chronic low back pain: a
      randomized controlled study.
AB  - STUDY DESIGN: A randomized controlled study investigated the effects of
      therapeutic climbing in patients with chronic low back pain. Before and after 4
      weeks of training, physical and mental well-being were measured by two
      questionnaires (36-Item Short Form Health Survey [SF-36]; Hannover Functional
      Ability Questionnaire for measuring back pain-related disability [FFbH-R]).
      OBJECTIVE: Therapeutic climbing has been suggested to increase muscular strength
      and perceived physical and mental well-being. This study focused on the
      psychological effects of therapeutic climbing and compared it with standard
      exercise therapy. SUMMARY OF BACKGROUND DATA: Therapeutic climbing has become
      increasingly popular in rehabilitation and its effects on muscular strengthening
      have been shown. Therapeutic climbing has also been suggested to yield
      psychological effects such as changes in attentional focus from pain to physical
      capabilities. To date, no controlled clinical trial has investigated these
      psychological effects and it is unclear whether therapeutic climbing is
      comparable or superior to other forms of exercise. METHODS: Twenty-eight patients
      with chronic low back pain conducted either a therapeutic climbing or a standard
      exercise regime. Each program took 4 weeks, including four guided training
      sessions per week. Before and after the program, patients answered two
      questionnaires assessing their physical and mental well-being. RESULTS: For the
      Hannover Functional Ability Questionnaire for measuring back pain-related
      disability, there was no difference before versus after or between the
      treatments. For the SF-36, both treatments showed significant improvements in 3/8
      subscales of the SF-36. In 2/8 subscales, only the participants of the
      therapeutic climbing improved and in 1/8 subscales the converse was true.
      Comparing both groups, significantly larger improvements were found after
      therapeutic climbing in two subscales of the SF-36: physical functioning and
      general health perception. CONCLUSION: The benefits of therapeutic climbing were
      comparable with those of a standard exercise regime. In two subscales of the SF
      36, the benefits of therapeutic climbing exceeded those of standard exercise
      therapy, primarily in perceived health and physical functioning of the patients.
      This finding demonstrates that therapeutic climbing is equivalent and partly
      superior to standard exercise therapy for patients with chronic low back pain.

PMID- 21192297
TI  - Cervical interbody fusion is enhanced by allogeneic mesenchymal precursor cells
      in an ovine model.
AB  - STUDY DESIGN: An experimental study using a sheep cervical spine interbody fusion
      model. OBJECTIVE: To compare allogeneic mesenchymal precursor cells combined with
      hydroxyapatite and tricalcium phosphate (HA/TCP) with HA/TCP alone or iliac crest
      autograft (AG) for cervical interbody fusion. SUMMARY OF BACKGROUND DATA: We
      investigated the effect of mesenchymal precursor cells on cervical fusion because
      of the shortcomings of using iliac crest (donor site morbidity), bone substitute
      (poor osteoinductive properties), and bone morphogenic proteins (serious
      complications). METHODS: Thirty ewes were divided randomly into four groups of
      six having C3-C4 anterior cervical discectomy and fusion using a Fidji cage
      packed with, AG, HA/TCP, HA/TCP containing 5 million MPCs, and HA/TCP containing
      10 million MPCs. MPCs were derived from a single batch of immuno-selected and
      culture-expanded MPCs isolated from bone marrow of out-bred sheep. The fifth
      group were nonoperated controls. Safety, fusion parameters, and biomechanics were
      assessed. RESULTS: No cell-related adverse events were observed. No significant
      differences were found between the five or 10 million MPC groups. Evaluation of
      fusion by CT scan at 3 months showed that 9 of 12 (75%) MPC-treated animals had
      continuous bony bridging compared with only 1 of 6 AG and 2 of 6 HA/TCP (P =
      0.019 and P = 0.044, respectively). By quantitative CT, density of new bone in
      MPC-treated animals was 121% higher than in HA/TCP (P = 0.017) and 128% higher
      than in AG (P < 0.0001). Functional radiology at 3 months revealed that MPC
      treated animals had significantly reduced macromotion at C3/4 compared with AG
      and HA/TCP groups combined (P = 0.007). CONCLUSION: Implantation of allogeneic
      MPCs when combined with HA/TCP and an interbody spacer facilitates new bone
      formation after discectomy without any cell-related complications. The earlier
      and dense new bone formation observed with MPCs relative to autograft and HA/TCP
      alone suggest that this approach may offer therapeutic benefit.

PMID- 21192299
TI  - Clinical results of total lumbar disc replacement regarding various aetiologies
      of the disc degeneration: a study with a 2-year minimal follow-up.

PMID- 21192298
TI  - The expression of tumor necrosis factor-alpha and CD68 in high-intensity zone of
      lumbar intervertebral disc on magnetic resonance image in the patients with low
      back pain.
AB  - STUDY DESIGN: Several recent studies suggest a high-intensity zone (HIZ) within
      the posterior annulu of lumbar intervertebral disc seen on T2-weighted magnetic
      resonance (MR) images represents the inflammation in the annulus, an annular
      tear, and/or vascular granulation tissue. It has not be reported yet whether
      there is the expression of tumor necrosis factor (TNF-alpha) and inflammatory
      cells appear in HIZ of intervertebral disc on MR images. OBJECTIVE: To study
      whether HIZ is a specific signal for the inflammatory reaction of painful
      intervertebral disc. SUMMARY OF BACKGROUND DATA: The presence of HIZ signal
      within the posterior annulus seen on sagittal T2-weighted spin-echo magnetic
      imaging sequences has already been used in the diagnosis of painful annular tears
      in the last decade. There have been studies suggesting that the presence of HIZ
      reflects inflammation in the annulus, an annular tear, and/or vascular
      granulation tissue. METHODS: Twenty-six consecutive patients with low back pain
      underwent MR images and discography (age range = 26-65 years; mean age = 47.5
      years; 16 men, 10 women). In all the patients, HIZ appeared in the involved
      intervertebral discs on T2-weighted MR images. Lumbar discography was usually
      performed on each patient for the discs L3-L4, L4-L5, and L5-S1. All patients
      received posterior lumbar interbody fusion procedures. The intervertebral disc
      specimens contained HIZ were excised en bloc during posterior interbody fusion.
      The distribution of TNF-alpha and CD68 in the intervertebral disc specimens
      within HIZ on MR images from 26 consecutive patients with low back pain and in
      the intervertebral disc specimens from five fresh cadavers were observed.
      RESULTS: The histologic study of the consecutive sagittal slices of the HIZ
      showed a lot of proliferated small round cells and fibroblasts. There were a lot
      of TNF-alpha positive cells and some CD68 positive cells in HIZ and the number of
      TNF-alpha and CD68 positive cells in HIZ was significantly higher than that in
      the annulus fibrosus around HIZ and in the control (P < 0.05). CONCLUSION: The
      results of this study indicate that HIZ may be a specific signal for the
      inflammatory reaction of painful intervertebral disc.

PMID- 21192301
TI  - Surgeons agree to disagree on surgical options for degenerative conditions of the
      cervical and lumbar spine.
AB  - STUDY DESIGN: This is a survey study designed to evaluate agreement among spine
      surgeons regarding treatment options for six clinical scenarios involving
      degenerative conditions of the cervical and lumbar spine. OBJECTIVES: The purpose
      was to evaluate whether or not surgeons agree on which cases require operative
      intervention and what type of surgery should be performed. SUMMARY OF BACKGROUND
      DATA: Agreement between spine surgeons on when to operate and what procedure to
      perform is a subject that has received increasing attention. This is an important
      question in the field of spine surgery, where "gold standards" that are based on
      large clinical trials are relatively sparse. METHODS: Six clinical vignettes were
      presented to 19 members of the Degenerative Spine Study Group. Each vignette was
      accompanied by a series of radiographs and/or magnetic resonance imagings,
      followed by treatment options in multiple-choice format. Two months later, the
      same vignettes were sent out with identical instructions except that they were
      now told they were treating a close family member. RESULTS: More than 76% of
      surgeons agreed on whether or not to recommend surgical intervention for the
      following four cases: lumbar degenerative spondylolisthesis with stenosis,
      cervical herniated nucleus pulposus, lumbar spondylosis, and lumbar herniated
      nucleus pulposus. Two scenarios had approximately 50% surgeon agreement: cervical
      stenosis and lumbar spondylolysis. However, despite good inter-rater agreement
      about who needed surgery, there was poor agreement regarding what procedure to
      perform if surgery was recommended. When repeating the survey in the setting of
      operating on a family member, only 17 (17.7%) of 96 recommendations were changed.
      CONCLUSION: Spine surgeons in this survey generally agreed on when to operate but
      failed to agree on what type of procedures to perform.

PMID- 21192302
TI  - Prevalence and predictors of pain in surgical treatment of adolescent idiopathic
      scoliosis.
AB  - STUDY DESIGN: Multicenter, prospective, consecutive clinical series. OBJECTIVE:
      To report on back pain and its association with patients' perceptions of
      appearance in a prospective cohort study of children before and after posterior
      spinal fusion for idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Back pain in
      idiopathic scoliosis has been noted to be reduced after surgery. However,
      uncertainty over its prevalence before and after operation persists. There is a
      paucity of data on correlations between patients' perceptions of their appearance
      and preoperative and postoperative pain. METHODS: We reviewed 1433 patients
      entered consecutively into the Prospective Pediatric Scoliosis Study, a database
      of children (8-22 years) undergoing operation for idiopathic scoliosis who have
      been followed for 1 and 2 years (n = 295) with the Scoliosis Research Society-22
      and Spinal Appearance Questionnaire instruments. RESULTS: Preoperative pain was
      reported by 77.9% of patients and 44% of surgeons. More preoperative pain
      correlated with older age (rho = -.140, P = 0.000), greater body mass index (rho
      = -0.168, P = 0.000), larger proximal thoracic curve rho = -0.086, P = 0.019),
      and a higher score on the Spinal Appearance Questionnaire Appearance (greater
      perception of spinal deformity, rho = -0.223, P = 0.000) and Appearance Desire
      scales (stronger desire to change the appearance of their spine, rho = -0.153, P
      = 0.000).Pain was reduced at 1 and 2 years after operation (P = 0.0002). Patients
      who perceived themselves as less deformed (rho = -0.284, P < 0.01) or had less
      desire to change their spinal appearance (rho = -0.183, P < 0.01) experienced a
      greater reduction in pain 2 years after operation.Preoperative analgesic use for
      back pain was high (28.8%) and remained high at 2 years after operation (29.5%)
      (P > 0.05). CONCLUSION: Back pain affects three-quarters of adolescents with
      idiopathic scoliosis and is reduced after posterior fusion. Patients who are
      overweight, older, and have larger proximal thoracic curve magnitudes report more
      preoperative pain. Patients who view themselves as more deformed tend to have
      more absolute pain, and less reduction in pain after operation.

PMID- 21192303
TI  - Defining and detecting missed ligamentous injuries of the occipitocervical
      complex.
AB  - STUDY DESIGN: Retrospective radiographic and clinical review of patients in a
      comprehensive trauma database. OBJECTIVE: The primary aim of this study was to
      detect occipitocervical complex (OCC) injuries initially missed at a level 1
      trauma center. SUMMARY OF BACKGROUND DATA: Recent case series demonstrate that
      OCC injuries are potentially survivable. Delay in diagnosis can lead to increased
      morbidity and mortality. METHODS: Normative maximum values that included 97.5% of
      the population were defined, with a sample of 251 consecutive normal computed
      tomographic (CT) scans for the Basion-Dens Interval (BDI), atlantooccipital
      interval, and lateral mass interval (LMI) of C1-C2. Subsequently, 844 cervical CT
      scans from consecutive polytrauma patients were reviewed for the evidence of OCC
      injury. Measurements greater than the normative maximum values were considered
      suspicious for injury. A BDI greater than 12 mm or a BDI greater than 10 mm with
      a confirmatory magnetic resonance imaging was considered a definite evidence of
      an OCC injury, as was an LMI 4 mm or greater with confirmatory magnetic resonance
      imaging. The electronic medical record was reviewed to determine whether an
      injury was detected on any final neuroradiology report or during follow-up.
      RESULTS.: Five patients had evidence of atlantooccipital dissociation (AOD), and
      two had atlantoaxial dissociation (AAD). Of these, three cases of AOD and two
      cases of AAD were missed on the final report by the neuroradiologist. The
      undiagnosed patients were subsequently diagnosed by orthopedic surgeons consulted
      for axial spine or other musculoskeletal trauma. No patients who were diagnosed
      with AAD or AOD in the electronic medical record were missed by using the
      criteria of BDI greater than 10 mm and LMI 4 mm or greater to define OCC
      injuries. CONCLUSION: OCC injuries can be missed even with standardized
      multidetector CT with multiplanar reconstructions. High-quality normative data
      used to determine a reliable picture archiving and communication system-based
      measurement of the OCC anatomy can detect ligamentous injuries initially missed
      in polytrauma patients.

PMID- 21192304
TI  - Transforaminal epidural clonidine versus corticosteroid for acute lumbosacral
      radiculopathy due to intervertebral disc herniation.

PMID- 21192306
TI  - Prolonged and repeated upright posture promotes bone formation in rat lumbar
      vertebrae.
AB  - STUDY DESIGN: Both forelimbs of rats were amputated and these rats were kept in
      the custom-made cages to keep prolonged and repeated upright posture. Changes of
      bone were observed in the lumbar vertebrae at three different time points after
      the surgery. OBJECTIVE.: To investigate the effect of prolonged and repeated
      upright posture on bone formation of rat lumbar vertebrae. SUMMARY OF BACKGROUND
      DATA: Previous studies show long-term and repeated load-induced bone formation,
      but there are no clear evidences to indicate whether or not long-term and
      repeated assumption of the upright posture could result in bone formation at rat
      lumbar vertebrae. METHODS: The forelimbs of 30 rats were amputated when they were
      1 month old. These rats were kept in the custom-made cages and were forced to
      stand upright on their hindlimbs and tails to obtain water and food. Normal rats
      of the same ages kept in regular cages were used as control. The rats were
      sacrificed at 5, 7, and 9 months after the surgery and lumbar vertebrae samples
      were harvested for micro-computed tomographic (CT), histological, and
      immunohistochemical studies. Total RNA isolated from these samples were used for
      real-time polymerase chain reaction of type I collagen (Col1alpha2), type X
      collagen (Col10alpha1), transforming growth factor-beta1 (TGF-beta1) and its
      related nuclear transcript factor runt-related transcription factor 2 (Runx2), as
      well as the biomarker of angiogenesis and vascular invasion, which is also a
      prerequisite for endochondral bone formation: vascular endothelial growth factor
      (VEGF). RESULTS: Micro-CT and histological studies showed increased trabecular
      bone density and increased osteoblast quantities of lumbar vertebrae after
      surgery. Immunostaining revealed increased protein expression of type I collagen,
      type X collagen, TGF-beta, and VEGF. Real-time polymerase chain reaction showed
      upregulated expression of Col1alpha2, Col10alpha1, VEGF, TGF-beta1, and Runx2
      mRNA. CONCLUSION: Upright posture induces bone acquisition in the rats' lumbar
      spine, primarily through the mode of the endochondral ossification, which is
      associated with increased loading, activated VEGF, and TGF-beta1 signaling.

PMID- 21192307
TI  - A comparison of unilateral and bilateral laminotomies for decompression of L4-L5
      spinal stenosis.
AB  - STUDY DESIGN: A retrospective review of clinical and radiographic data was
      performed at a single institution. OBJECTIVES: To compare clinical and radiologic
      outcomes between unilateral and bilateral laminotomies for bilateral
      decompression in patients with L4-L5 spinal stenosis. SUMMARY OF BACKGROUND DATA:
      Laminotomy has been shown to be comparable with laminectomy with the advantage of
      potentially maintaining more stability by preserving more of the osseous
      structures. However, the comparison between unilateral and bilateral laminotomies
      is available only for short-term follow-up. METHODS: Fifty-three patients at one
      institution having decompressive surgery for L4-L5 spinal stenosis, including
      grade 1 degenerative spondylolisthesis without instability, were entered into
      this study with a minimum of 3-year follow-up. Clinical outcomes were assessed
      with visual analog scale for back and leg pain and the Oswestry disability index.
      Radiographic measurements were performed and included translational motion,
      angular motion, and epidural cross-sectional area. RESULTS: The average age of
      the patients was 62.4 years (range: 31-82). The mean follow-up period was 49.3
      months (range: 40-61). Clinical outcomes and complication rates were similar in
      both groups. Intraoperative blood loss and operative time were less in the
      unilateral laminotomy group. Radiographically, the amount of increased
      translational motion was significantly increased in the bilateral laminotomy
      group (P 0.012), but the amount of increased angular motion was not significantly
      different (P 0.195) between the two groups. Postoperative radiographic
      instability was detected more frequently in bilateral laminotomy group than in
      the unilateral group, without statistical significance. CONCLUSIONS: Both
      unilateral and bilateral laminotomies provide sufficient decompression of spinal
      stenosis and excellent pain reduction. However, unilateral laminotomy can be
      performed with shorter operative times and less blood loss. Radiologically, the
      use of a unilateral laminotomy induces less translational motion increase after
      surgery; thus, it may reduce the risk of late instability when compared with a
      bilateral laminotomy.

PMID- 21192309
TI  - Remodeling of C2 facet deformity prevents recurrent subluxation in patients with
      chronic atlantoaxial rotatory fixation: a novel strategy for treatment of chronic
      atlantoaxial rotatory fixation.
AB  - STUDY DESIGN: A retrospective case series. OBJECTIVE: To propose a novel
      treatment strategy for chronic atlantoaxial rotatory fixation (AARF). SUMMARY OF
      BACKGROUND DATA: Treatment strategy for chronic or recurrent AARF remains
      controversial. We have previously reported that a deformity of the superior facet
      of the axis (C2 facet deformity), which is frequently observed in patients with
      chronic AARFs, is a risk factor for recurrent dislocation. In this article, we
      report seven consecutive cases of chronic AARF who underwent closed manipulation
      followed by external halo fixation and maintained good reduction with the
      remodeling of the C2 facet deformity. METHODS: Seven girls with a chronic AARF
      who sustained torticollis for an average of 4.6 months after the onset were
      referred to our clinic. Closed manipulation by careful manipulation under general
      anesthesia followed by external immobilization with a halo vest was performed in
      all cases. Radiographic findings and clinical courses were retrospectively
      reviewed with approvals by the institutional review board. RESULTS: Three
      dimensional computed tomography images before reduction revealed persistent
      atlantoaxial subluxation and the C2 facet deformity in the dislocated side in all
      cases. Follow-up three-dimensional computed tomographic scans demonstrated the
      remodeling of the C2 facet deformity at an average of 2.8 months after successful
      reduction of subluxation. Subsequently, the halo vests were removed and gentle
      neck range of motion exercise was started in all cases. The normal cervical range
      of motion was obtained 2 weeks after the removal of halo vests in five cases,
      whereas the range of motion remained limited in two cases. At a mean follow-up of
      17.4 months, neither symptoms nor recurrence of subluxation occurred in all
      cases. CONCLUSION: Chronic irreducible and recurrent unstable AARF can be managed
      successfully by careful closed manipulation followed by halo fixation, if the C1
      and C2 have not been osseously fused. The remodeling of the C2 facet deformity
      detected on follow-up CT scans can be a useful radiographic parameter to
      determine the appropriate period of halo fixation in this new treatment strategy
      obviating the need for surgical intervention.

PMID- 21192310
TI  - The role of proton pump inhibitors on early mycophenolic acid exposure in kidney
      transplantation: evidence from the CLEAR study.
AB  - INTRODUCTION: Proton pump inhibitors (PPIs) are often prescribed
      posttransplantation to prevent gastrointestinal complications. A series of recent
      studies have reported a relationship between PPI comedication and decreased
      mycophenolic acid (MPA) exposure. The objective of this subanalysis of the CLEAR
      data set was to determine the impact of PPI therapy on full MPA area under the
      curve exposures at Day 5 post kidney transplant. MATERIAL AND METHODS: Patients
      were randomized to receive either intensified dosing of mycophenolate mofetil
      (1.5 g twice daily on Days 1-5, then 1.0 g twice daily, n = 68) or standard
      dosing (1.0 g twice daily, n = 67). All recipients received tacrolimus and
      prednisone. RESULTS: In the modified intention-to-treat population, 57.9% of
      patients (73 of 126) received PPI therapy. The most frequently administered
      therapies were pantoprazole and omeprazole. There was no significant difference
      in mean MPA area under the curve at Day 5 for patients receiving PPI therapy as
      compared with those not receiving PPI therapy (51.3 versus 55.8 mg.h/L, P =
      0.265). However, the MPA concentration-time curve analysis demonstrated a
      significant decrease in MPA concentrations at 2 hours and 12 hours postdose in
      patients receiving PPI therapy (P = 0.0009 and P = 0.034). No significant
      differences were identified in the 3-g arm specifically. In the multivariate
      model, only serum creatinine and albumin significantly predicted MPA area under
      the curve less than 30 mg.h/L at Day 5. DISCUSSION AND CONCLUSION: PPI therapy in
      combination with mycophenolate mofetil does not appear to have a significant
      impact on full MPA exposure. Because MPA pharmacokinetics were not significantly
      impacted when a 3-g, 5-day loading dose of mycophenolate mofetil was used in
      combination with PPI therapy, this strategy may be required for adequate MPA
      exposure whether or not a patient receives PPI comedication.

PMID- 21192311
TI  - Adherence to HIV therapeutic drug monitoring guidelines in The Netherlands.
AB  - BACKGROUND: Therapeutic drug monitoring (TDM) is recommended in several
      international HIV treatment guidelines. The adherence of clinicians to these
      recommendations is unknown. The authors evaluated the adherence to the Dutch TDM
      guideline of 2005. METHODS: From the ATHENA cohort study, three scenarios were
      selected for which the guideline recommended TDM: 1) start of a combination of
      lopinavir/ritonavir + efavirenz or nevirapine (drug-drug interaction); 2) start
      of efavirenz (routine TDM); and 3) use of nelfinavir during pregnancy. For each
      scenario, we determined the proportion of patients for whom TDM was performed.
      Multivariable logistic regression modeling was used to identify determinants for
      the use of TDM. RESULTS: The adherence to the TDM guideline was 46.7% in patients
      who started lopinavir/ritonavir plus efavirenz or nevirapine; 9.5% for patients
      who started efavirenz; and 58.5% for patients who used nelfinavir during
      pregnancy. Patients treated in clinics that had a TDM assay available locally and
      patients treated in academic clinics were more likely to receive TDM. A higher
      baseline HIV viral load was another significant predictor for the performing TDM.
      CONCLUSION: The adherence of clinicians to the Dutch TDM guidelines varied from
      low to moderate for the three investigated TDM scenarios. This study identifies
      several determinants for the use of TDM, which may be useful information for
      those responsible for generating TDM guidelines.

PMID- 21192312
TI  - Nicotine and metabolites in paired umbilical cord tissue and meconium specimens.
AB  - Umbilical cord tissue was studied as a means of detecting prenatal exposure to
      nicotine. This was accomplished by comparing the presence and concentration of
      nicotine as well as nicotine metabolites in both umbilical cord tissue and paired
      meconium samples with maternal smoking histories obtained by self-report.
      Nicotine and metabolites (cotinine, 3-hydroxycotinine, nornicotine, and
      anabasine) were detected and quantitated using liquid chromatography-tandem mass
      spectroscopy. Between June and September 2009, 19 women with a tobacco exposure
      history (either first- or second-hand tobacco smoke exposure during pregnancy)
      were consented for the study. A questionnaire was completed to document nicotine
      exposure during each trimester of pregnancy. All infants were delivered at term
      (38 weeks or greater) and paired umbilical cord tissue (10-cm segment or greater)
      and meconium were obtained. Nicotine and 3-hydroxycotinine were most prominent in
      meconium, whereas cotinine and 3-hydroxycotinine were most prominent in the
      umbilical cord. Concentrations of all three analytes were generally higher in
      meconium. Nornicotine was detected only in meconium, at very low concentrations,
      and anabasine was not detected in either specimen. All analyte concentrations
      were lowest when the mother stated she quit smoking early in pregnancy or had
      only second-hand exposure, and detection was poor if exposure was limited to the
      first or second trimesters. Although different nicotine and metabolite patterns
      exist in meconium versus umbilical cord tissue, this work indicates that either
      specimen can be used to detect third-trimester fetal nicotine exposure.

PMID- 21192313
TI  - Modulators of very low voriconazole concentrations in routine therapeutic drug
      monitoring.
AB  - Very low voriconazole concentrations are commonly observed during therapeutic
      drug monitoring. Possible mechanisms include inappropriate dose selection, rapid
      metabolism (as a result of genetic polymorphisms or enzyme induction), and also
      nonadherence. We aimed to develop a method to distinguish between rapid
      metabolism of and nonadherence to voriconazole by quantification of voriconazole
      metabolites. In addition, the relevance of common genetic polymorphisms of
      CYP2C19 was assessed. In a retrospective study, samples with voriconazole
      concentrations 0.2 MUg/mL or less in routine therapeutic drug monitoring (as
      quantified by high-performance liquid chromatography) were evaluated.
      Voriconazole and its N-oxide metabolite were quantified in residual blood using a
      highly sensitive liquid chromatography-tandem mass spectroscopy method (lower
      limit of quantitation = 0.03 MUg/mL). Genetic polymorphisms of CYP2C19 were
      determined by real-time polymerase chain reaction using the hybridization probe
      format and the polymerase chain reaction-random fragment length polymorphism
      format. A total of 747 routine therapeutic drug monitoring plasma/blood samples
      of 335 patients treated with systemic voriconazole were analyzed and in 18.7% of
      all samples, voriconazole concentrations 0.2 MUg/mL or less were found. In 32
      samples (30 patients) with adequate dosage and timing of blood withdrawal,
      nonadherence was strongly suspected in seven patients because voriconazole-N
      oxide concentrations were below 0.03 MUg/mL, which was not observed in a
      reference group of 51 healthy volunteers with controlled drug intake. In 10
      patients, of whom EDTA blood was available, the ultrarapid metabolizer genotype
      (CYP2C19*1?*17, CYP2C19*17?*17) was found in 80% and its prevalence was
      significantly higher as compared to a reference group (P = 0.02). In conclusion,
      quantification of voriconazole-N-oxide allowed for detection of suspected
      nonadherence in one of four patients with very low voriconazole concentrations.
      In the remaining patients, ultrarapid metabolism resulting from the CYP2C19*17
      polymorphism appears to play a major role. Thus, in the case of voriconazole
      therapy failure, both nonadherence and genetic factors have to be considered.

PMID- 21192314
TI  - Light transmittance aggregometry induced by different concentrations of adenosine
      diphosphate to monitor clopidogrel therapy: a methodological study.
AB  - Light transmission aggregation (LTA) is considered the reference method to
      identify residual platelet reactivity (RPR) in high-risk patients with coronary
      artery disease on clopidogrel treatment. An international standardization of this
      technique is still ongoing and different concentrations of adenosine diphosphate
      (ADP) as the agonist for LTA have been used to evaluate the inhibitory effect of
      clopidogrel treatment. To evaluate RPR, LTA was performed using different ADP
      concentrations (2, 5, 10, and 20 MUmol/L) in 466 high-risk patients with coronary
      artery disease on dual antiplatelet therapy who underwent percutaneous coronary
      intervention and in 46 healthy subjects. A VerifyNow P2Y12 assay was assessed as
      a point-of care system. Imprecision studies showed higher coefficients of
      variation for LTA by 2 and 5 MUmol/L ADP (healthy subjects: 4.7% and 3.9%;
      patients: 6.8% and 5.2%, respectively) in comparison with those obtained
      determining LTA using 10 and 20 MUmol/L ADP (healthy subjects: 2.2% and 2.3%;
      patients: 2.7% and 3.1%, respectively). In patients, a significant difference (P
      < 0.0001) between mean values of LTA obtained with all ADP concentrations was
      found, even if LTA data were significantly correlated (at least: rho = 0.88, P <
      0.0001). However, data from 10 and 20 MUmol/L ADP LTA were very similar and
      highly concordant (k = 95.9%). All agreements were significant (for all P <
      0.0001), in particular the agreement between 10 and 20 MUmol/L ADP LTA was very
      good (k = 0.86, P < 0.0001). A moderate agreement between VerifyNow and both 10
      and 20 MUmol/L ADP LTA was observed. LTA by 10 and 20 MUmol/L ADP gave equivalent
      percentages of aggregation and highly concordant results in terms of RPR in
      patients with coronary artery disease on clopidogrel. Significant concordant
      results were observed between both 10 and 20 MUM ADP LTA and VerifyNow. This
      suggests that a concentration of 10 MUmol/L ADP may be considered adequate for
      the identification of RPR of patients on clopidogrel and should be preferred for
      standardization LTA.

PMID- 21192315
TI  - Evaluating performance of a decision support system to improve methotrexate
      pharmacotherapy in children and young adults with cancer.
AB  - The management of high-dose methotrexate (MTX) therapy in patients with cancer
      depends on the routine monitoring of drug exposures in conjunction with
      leucovorin (LV), urine pH, patient hydration, and other clinical indices of
      patient well-being. A key factor in patient oversight is the facilitation of MTX
      clearance to minimize drug-related toxicity. The aim of this investigation was to
      evaluate the performance of a clinical decision support system and Bayesian
      forecasting algorithm in the prediction of MTX concentrations and assessment of
      LV dosing requirements in pediatric and young adult patients with cancer based on
      the current practice at the Children's Hospital of Philadelphia. Fifty patients
      ranging in age from 8 months to 21 years (weight range, 7.6-163.3 kg)
      contributing 80 total dosing events (183 MTX serum concentrations) were studied.
      The forecasting model was able to consistently predict future MTX concentrations
      with the knowledge of one prior concentration and continued to improve with
      additional concentration data made available through daily therapeutic drug
      monitoring. Precision was good at 12.9% with low bias at 2.2%. Comparison between
      the decision support system recommendations for LV rescue relative to the actual
      LV administration was also made. Sixteen patients would have initiated rescue
      therapy earlier, seven patients would have received a larger dose (42 smaller),
      and LV would have been given less often for 37 patients. The forecasting
      algorithm in the MTX dashboard was reasonably accurate in predicting MTX
      concentrations and should improve further as the underlying model and prediction
      algorithm evolves. This decision support system can be useful in helping
      physicians decide if a patient is clearing MTX as expected or if more aggressive
      rescue therapy is warranted.

PMID- 21192316
TI  - Conversion from Prograf to Advagraf among kidney transplant recipients results in
      sustained decrease in tacrolimus exposure.
AB  - BACKGROUND: Advagraf is a slow release form of tacrolimus with once-daily
      formulation. The potential advantages of Advagraf are better adherence and a
      safer profile by avoiding toxic peak concentrations. In this study, we evaluated
      the required daily doses of tacrolimus and subsequent blood levels on conversion
      from Prograf to Advagraf among kidney transplant recipients. METHODS: We
      retrospectively reviewed data from 55 patients for whom a switch from Prograf to
      Advagraf was identified. Tacrolimus daily doses and concomitant blood levels were
      analyzed at several time points ranging from 3 months before to 6 months after
      conversion. RESULTS: We observed a significant increase in tacrolimus daily
      doses, starting with a dose of 0.063 mg/kg of Prograf, increasing up to 0.081
      mg/kg of Advagraf at 6 months (P<0.0001). After conversion, we observed a quick
      and sustained decrease in trough tacrolimus levels, decreasing from 8.05 ng/mL at
      day 0 to 6.30 ng/mL at day 180 (P=0.0009). At 6 months, 35% of patients
      experienced a decrease in trough levels of more than 30%. Creatinine values
      remained stable over time, and no patient experienced an acute rejection episode.
      CONCLUSIONS: Contrary to the manufacturer instructions, we found a significant
      decrease in tacrolimus exposure after switching to Advagraf. Therefore, the
      switch from Prograf to Advagraf should be performed under close medical
      supervision.

PMID- 21192317
TI  - The survival of myoblasts after intramuscular transplantation is improved when
      fewer cells are injected.
AB  - BACKGROUND: Myoblast transplantation has long been studied as a potential therapy
      for Duchenne muscular dystrophy as the incorporation of donor myoblasts into host
      muscle allows the production of functional dystrophin protein. However, the
      clinical feasibility of this approach is limited by the poor survival of the
      donor cells in the weeks after transplantation. It has recently been determined
      that the intramuscular transplantation of large numbers of cells can lead to the
      formation of ischemic necrosis in the center of these cell masses. For this
      reason, the relationship between donor cell survival and the number of cells
      transplanted was investigated. METHODS: Myoblasts were prepared from the hind
      limb muscles of male C57BL/10Sn mice and transplanted into the tibialis anterior
      muscles of female mdx mice at one of the following amounts: 10, 10, 10, or 10
      cells. The survival of the transplanted cells was analyzed using a Y chromosome
      specific qPCR. RESULTS: It was found that donor cell survival was improved 1 week
      after transplantation when fewer myoblasts were transplanted, including the
      observation of donor cell proliferation after the transplantation of 10
      myoblasts. However, concentration effects and long-term survival complicate the
      interpretation of these results. CONCLUSIONS: These results indicate that early
      donor myoblast survival was dependent on the number of cells transplanted and the
      volume of liquid used to deliver them into the muscle. We believe that this
      finding has implications for the design and interpretation of future
      experimentation relating to intramuscular cell therapies.

PMID- 21192318
TI  - The effect of cinacalcet on bone remodeling and renal function in transplant
      patients with persistent hyperparathyroidism.
AB  - BACKGROUND: Parathyroidectomy is associated with renal functional losses in
      transplant patients; cinacalcet offers an attractive alternative. METHODS: We
      performed a prospective observational study in 58 patients with persisting
      hyperparathyroidism after renal transplantation (Ca>=2.6 mmol/L) and impaired
      renal transplant function (estimated glomerular filtration rate [eGFR] <50
      mL/min). The patients received 30 to 90 mg cinacalcet for 12 months with the
      target to normalize serum Ca. We measured parathyroid hormone (PTH), serum Ca,
      serum phosphorus, alkaline phosphatase, bone-specific alkaline phosphatase,
      osteocalcin, and telopeptide at 0, 1, 2, 3, 6, 9, and 12 months of cinacalcet
      treatment. Fractional excretion of calcium and phosphorus (n=24) were monitored
      at 0 and 1 month. RESULTS: At inclusion, creatinine was 181+/-70 MUmol/L, eGFR
      43+/-19 mL/min, PTH 371+/-279 pg/mL, and Ca 2.73+/-0.22 mmol/L. We observed
      nephrocalcinosis in 58% of biopsied patients at enrollment. After cinacalcet, Ca
      decreased significantly and normalized at nearly any measurement. Phosphorus
      increased significantly at months 1, 9, and 12. PTH decreased significantly, but
      only at months 9 and 12 and did not normalize. Bone-specific alkaline phosphatase
      increased significantly (>normal) by month 12. eGFR decreased and serum
      creatinine increased at all time points. The Delta(creatinine) % increase
      correlated significantly with the Delta(PTH) % decrease at month 1 and 12.
      Telopeptide and alkaline phosphatase correlated with PTH and telopeptide also
      correlated with serum creatinine. CONCLUSION: Calcium-phosphorus homeostasis in
      hypercalcemic renal transplant patients normalizes under cinacalcet and PTH
      decreases, albeit not to normal. The renal functional decline could be PTH
      mediated, analogous to the effects observed after parathyroidectomy.

PMID- 21192319
TI  - Interpretation of positive flow cytometric crossmatch in the era of the single
      antigen bead assay.
AB  - BACKGROUND: Prognosis of renal transplants with positive flow cytometric
      crossmatch (FCXM) remains controversial. METHODS: We analyzed the outcome of
      these kidney transplant recipients by human leukocyte antigen (HLA) donor
      specific antibodies (HLA-DSA) using single-antigen bead (SAB) assays in major
      histocompatibility complex classes I and II. We compared them with controls with
      a negative FCXM. RESULTS: Forty-five patients consecutively transplanted with a
      positive FCXM had significantly more acute rejection episodes than the control
      patients (33.3% vs. 8.9%, P=0.002). Risk of acute rejection was increased with
      day 0 (D0) positive T-cell FCXM (odds ratio [OR]=9.04, P=0.002), D0 positive B
      cell FCXM (OR=7.43, P=0.02), and D0 HLA-DSA identified by SAB assay (OR=6.5,
      P=0.03). The 21 patients with D0 positive FCXM and D0 HLA-DSA had more acute
      rejection (62%, P=0.0001) and a lower estimated glomerular filtration rate 1-year
      posttransplantation (P=0.0001), when compared with controls. Mainly anti-Cw and
      anti-DP HLA-DSA were found in patients displaying acute rejection. The remaining
      FCXM-positive patients displayed short-term outcomes similar to controls. The
      presence of HLA-DSA detected only by the SAB assay in the context of a negative
      FCXM crossmatch was not associated with increased risk of acute rejection.
      CONCLUSION: Identification of HLA-DSA in D0 sera by the two sensitive techniques
      FCXM and SAB assay indicates which patients are at highest risk of subsequent
      acute allograft rejection and chronic allograft dysfunction.

PMID- 21192320
TI  - Naked small interfering RNA of caspase-3 in preservation solution and autologous
      blood perfusate protects isolated ischemic porcine kidneys.
AB  - BACKGROUND: Ischemia-reperfusion injury (IRI) plays key roles in graft viability
      and posttransplantation function. Caspase-3 associated with apoptosis and
      inflammation is up-regulated by IRI. We propose that naked small interfering RNA
      (siRNA) targeting caspase-3 may prevent IRI and improve kidney preservation.
      METHODS: Porcine kidneys were retrieved after 10-min warm ischemia and flushed
      with 500 mL hyperosmolar citrate. Caspase-3 siRNA was administered directly into
      the renal artery in hyperosmolar citrate solution (3 MUg/ml) with the renal vein
      clamped and into autologous blood (0.15 MUg/ml), both of which were stored for 24
      hr on ice. The kidneys were reperfused with oxygenated autologous blood for 3 hr
      on an isolated organ perfusion system to assess renal function. RESULTS: In the
      siRNA-treated group, the expression of 32-kDa caspase-3 precursor and 17-kDa
      active subunit was down-regulated by 30% and 56%, respectively, with 40%
      reduction in active caspase-3+ cells. Consequently, apoptotic cells in the renal
      cortex were significantly decreased by 47%, whereas inflammatory cells were only
      marginally reduced by 26%. Caspase-3 siRNA also doubled oxygen consumption and
      significantly neutralized perfusate pH. Renal blood flow was gradually increased
      from 5 min to 3 hr by caspase-3 siRNA and marginally improved at the end of 3-hr
      reperfusion by 45%. CONCLUSIONS: The administration of caspase-3 siRNA directly
      into the kidney and hemoperfusate during cold preservation improved IRI with
      reduced caspase-3 and apoptosis, and better renal oxygenation and acid-base
      homeostasis. This proof of principle experiment using a novel siRNA therapy in
      large animal organs provides valuable data for human kidney transplantation.

PMID- 21192321
TI  - Depletion of alveolar macrophages abrogates prolongation of cardiac allograft
      survival induced by intratracheal delivery of alloantigen.
AB  - BACKGROUND: We previously showed that pretreatment with intratracheal delivery
      (ITD) of alloantigen induced prolonged cardiac allograft survival and generated
      regulatory cells in mice. In this study, we examined the role of alveolar
      macrophages (AM) in our ITD model. METHODS: Some CBA mice were given ITD of
      C57BL/6 splenocytes and underwent transplantation of C57BL/6 hearts 7 days later.
      In others, AM were depleted with clodronate-loaded liposomes 3 days before ITD.
      In adoptive transfer studies, whole splenocytes were obtained from ITD-treated
      CBA mice and administered to naive CBA secondary recipients, which were given
      C57BL/6 hearts immediately afterward. Interleukin-10 concentrations in
      bronchoalveolar lavage fluid were assessed by enzyme-linked immunosorbent assays.
      Immunohistologic and flow cytometric studies were performed after ITD. RESULTS:
      C57BL/6 splenocytes given by ITD were ingested by AM in 2 days and undetectable
      in paratracheal lymph nodes or spleen tissue. CBA mice given ITD of C57BL/6
      splenocytes had markedly prolonged allograft survival (median survival time
      [MST], 86 days), whereas naive CBA mice rejected allografts acutely (MST, 8
      days). AM-depleted, ITD-treated mice also rejected allografts (MST, 5.5 days).
      Naive secondary recipients given adoptive transfer of splenocytes from ITD
      treated mice had prolonged allograft survival (MST, >100 days), whereas secondary
      recipients given adoptive transfer of splenocytes from AM-depleted, ITD-treated
      mice rejected the grafts (MST, 15.5 days). Interleukin-10 expression in
      bronchoalveolar lavage fluid was down-regulated in AM-depleted mice compared with
      naive mice. CONCLUSIONS: AM have an important role in the induction of regulatory
      cells in our model of ITD of alloantigen.

PMID- 21192322
TI  - Embryonic pig pancreatic tissue for the treatment of diabetes: potential role of
      immune suppression with "off-the-shelf" third-party regulatory T cells.
AB  - BACKGROUND: Xenogeneic embryonic pancreatic tissue can provide an attractive
      alternative for organ replacement therapy. However, immunological rejection
      represents a major obstacle. This study examines the potential of regulatory T
      cells (Tregs) in the prevention of E42 pancreas rejection. METHODS: To develop
      new approaches to combat rejection, we evaluated engraftment, growth, and
      development of E42 pig pancreatic tissue in mice treated with ex vivo expanded
      Tregs in combination with T-cell debulking and the conventional immunosuppressive
      drugs, rapamycin and FTY720. RESULTS: Transplantation of E42 pig pancreas into
      C57BL/6 mice immunosuppressed by this protocol resulted in complete rejection
      within less than 6 weeks. In contrast, additional treatment with a single
      infusion of ex vivo expanded third-party Tregs markedly delayed the onset of
      graft rejection to 10 weeks. The infusion of Tregs was associated with a
      significant reduction in CD4 and CD8 expansion in the lymph nodes and other
      peripheral organs at the priming stages after implantation. Freezing and thawing
      of the Tregs did not affect their efficacy, indicating the potential of Tregs
      banking. CONCLUSION: Considering the technical difficulties encountered in the
      generation of Tregs from patients or from specific donors, our results
      demonstrate the feasibility of using "off-the-shelf" fresh or frozen third-party
      Tregs to control rejection in organ transplantation.

PMID- 21192323
TI  - I recently had a mild stroke and am making a good recovery.  I maintain a pretty
      healthy diet and I exercise regularly, but I'm wondering if I need to change my
      routine because of the stroke and to help prevent another one.  Are there other
      precautions I should take because I'm at a higher risk now that I've already had
      one stroke?

PMID- 21192324
TI  - [New type hearing aids thanks to psychoacoustics].

PMID- 21192325
TI  - Sensitive and specific neuropsychological assessments of the behavioral effects
      of epilepsy and its treatment are essential.

PMID- 21192326
TI  - Update 1 of: Electrochemical approach to the mechanistic study of proton-coupled
      electron transfer.

PMID- 21192327
TI  - Medical education in an age of complexity, uncertainty and reflection. A coda to
      the Flexner centenary.

PMID- 21192328
TI  - Broad church or bunfight? Possibilities for progress in medical education.

PMID- 21192329
TI  - Abraham Flexner and the evolution of the modern medical school.

PMID- 21192330
TI  - Developmental aspects of medical competency and training: issues of curriculum
      design.

PMID- 21192331
TI  - Revolution or evolution? Putting the Flexner Report in context.

PMID- 21192332
TI  - Medical education in the 21st century: what would Flexner ask?

PMID- 21192333
TI  - Medical and health care professional education in the 21st century:
      institutional, national and global perspectives.

PMID- 21192334
TI  - Hope for keratoconus.

PMID- 21192336
TI  - Electronic health records definitions and acronyms.

PMID- 21192335
TI  - Practitioner attitudes on children and contact lenses.

PMID- 21192337
TI  - To sign or not to sign: recognizing insurance contracts as  business decisions.

PMID- 21192338
TI  - Changes in free water fraction and aquaporin function with dwell time during
      continuous ambulatory peritoneal dialysis.
AB  - Diffusive (K(BD), A0/Deltax(t)) transport parameters and sieving coefficients (S)
      for small solutes and free water fraction (FWF), that is, the fraction of total
      water flow that is transported through aquaporins, were assessed as functions of
      dwell time t for 35 continuous ambulatory peritoneal dialysis patients using
      glucose 3.86% dialysis fluid.The individual values of the unrestricted pore area
      over diffusion distance, A0/Deltax(t), were estimated using the mixed effects
      nonlinear regression and applied for evaluation of S(t) for sodium and FWF(t).
      FWF decreased on average from the initial 51% of the total transcapillary water
      flow to 36% at 120 min, whereas the small pore water fraction and sodium sieving
      coefficient increased. Our results were consistent with the three-pore model if
      the contribution of the transcellular pores (alpha(TP)) at the beginning of dwell
      study was doubled and later decreased to the standard value of 0.02.We conclude
      that transport characteristics of fluid and small solutes should be considered as
      time-dependent variables during the peritoneal dialysis.

PMID- 21192339
TI  - Should you take the plunge into social media?

PMID- 21192340
TI  - Building a successful practice is a team sport.

PMID- 21192341
TI  - Targeting the oncogenic role of miRNA in human cancer using naturally occurring
      compounds.
AB  - Micro-RNAs (miRNAs) are small RNA molecules that regulate the expression of genes
      involved in development, growth, proliferation and apoptosis. In cancer several
      miRNAs have been functionally classified as oncogenes or tumour suppressers or
      act to regulate transcription factors, like nuclear factor kappa B and NF-E2
      related factor 2, in cancers such as leukaemia, breast and colorectal. Therefore,
      it has been proposed that manipulating miRNA regulation may be a novel avenue for
      developing efficient therapies against cancer. In this issue, Li and colleagues
      describe a novel way of targeting miRNA, by using a naturally occurring anti
      cancer compound found in mistletoe which they showed to down-regulate miR-135a&b,
      which target the 3' untranslated region of adenomatous polyposis coli gene, the
      inactivation of which is a major initiating event in colorectal tumourigenesis.
      This commentary aims to discuss the regulatory mechanisms of miRNA synthesis and
      the potential outcomes for using naturally occurring compounds antioxidants or
      cellular antioxidant pathways to target miRNA for therapeutic intervention.

PMID- 21192342
TI  - Prevalence of cardiovascular risk factors in an urban adult population from
      southern Spain. IMAP Study.
AB  - AIMS: To study the prevalence of cardiovascular risk factors in an urban
      population of Malaga, Spain and its relationship with educational level. METHODS:
      A cross-sectional study was performed with a random representative sample of 2270
      individuals from the adult population (18-80 years) from a specific Health-Care
      Centre in Malaga City. All participants underwent a clinical interview, including
      social-demographical information and a physical examination. A blood sample was
      also drawn. RESULTS: The mean age of the participants was 43.6 +/- 15.6 years and
      57.6% had a low educational level. The prevalence of cardiovascular risk factors
      was: smoking 27.7%, hypertension 33.1%, diabetes 7.1% and dyslipidaemia 65.4%.
      Over 60% were either overweight or obese, and 76.7% had a sedentary lifestyle.
      Except for smoking and a low-HDL cholesterol, the prevalence of the other
      cardiovascular risk factors increased with age. A low educational level was
      associated with a high prevalence of cardiovascular risk factors, and this
      association was significant with regard to smoking, obesity, abdominal obesity
      and hypertriglyceridaemia. CONCLUSIONS: The population studied presents a high
      prevalence of cardiovascular risk factors, especially dyslipidaemia and obesity.
      The low academic level was associated with an increased prevalence of smoking,
      obesity and dyslipidaemia. People with a low socio-cultural level are a priority
      target for introducing policies to prevent and control cardiovascular disease.

PMID- 21192343
TI  - [Vertical dimension in the treatment of the edentulous patient].
AB  - Determining and recording appropriate occlusal vertical dimension (OVD) in the
      treatment of the edentulous patient is an important but critical procedure in
      practice. Incorrect determination of the OVD may result in failure of complete
      denture treatment. Many methods have been advocated to determine the vertical
      dimension in edentulous patients. However, there is no single precise scientific
      method for determining the correct OVD. These methods include the use of
      physiologic rest position, swallowing, phonetic, aesthetic, facial measurements.
      A combination of some of them is recommended for a simplified clinical
      determination. Moreover, the application of several accepted tests is advocated
      to verify the established OVD.

PMID- 21192345
TI  - Exon sequencing and association analysis of EPHX1  genetic variants with
      maintenance warfarin dose in a  multiethnic Asian population.
AB  - BACKGROUND AND OBJECTIVES: Warfarin inhibits vitamin K epoxide reductase, of
      which microsomal epoxide hydrolase is a putative member. Several studies have
      found signals of association with warfarin maintenance dose in the EPHX1 gene.
      The aim of this study was to determine the effects of EPHX1 variants on warfarin
      maintenance dose in a multiethnic Asian population. METHODS: We sequenced the
      exons of EPHX1 using PCR and direct sequencing in 279 patients consisting of
      three major ethnic groups receiving maintenance warfarin with a stable
      international normalized ratio. The effects of EPHX1 variants were assessed using
      multiple linear regression. RESULTS: An association between an intronic SNP
      rs1877724 and warfarin maintenance dose was found, with homozygous variant
      carriers requiring approximately 0.5 mg/day lower than wild type and
      heterozygotes after adjustment for covariates. However, its contribution is
      small, explaining only an additional 0.8% of the dose variability. Rare variants
      were pooled but there was no association between their presence and warfarin
      maintenance dose. However, the presence of noncoding rare SNPs was significantly
      associated with warfarin maintenance dose. CONCLUSION: Despite a significant
      finding in rs1877724, which concurs with an earlier study, overall, genetic
      variants in EPHX1 do not have a clinically significant impact on warfarin dose
      requirements in our population.

PMID- 21192344
TI  - CYP2C19 variation and citalopram response.
AB  - OBJECTIVE: Variations in cytochrome P450 (CYP) genes have been shown to be
      associated with both accelerated and delayed pharmacokinetic clearance of many
      psychotropic medications. Citalopram is metabolized by three CYP enzymes. CYP2C19
      and CYP3A4 play a primary role in citalopram metabolism, whereas CYP2D6 plays a
      secondary role. METHODS: The Sequenced Treatment Alternatives to Relieve
      Depression sample was used to examine the relationship between variations in the
      CYP2C19 and CYP2D6 genes and remission of depressive symptoms and tolerance to
      treatment with citalopram. The primary analyses were of the White non-Hispanic
      patients adherent to the study protocol (n= 1074). RESULTS: Generally, patients
      who had CYP2C19 genotypes associated with decreased metabolism were less likely
      to tolerate citalopram than those with increased metabolism, although this
      difference was not statistically significant (P = 0.06). However, patients with
      the inactive 2C19*2 allele had significantly lower odds of tolerance (P = 0.02).
      Patients with the poor metabolism CYP2C19 genotype-based category who were
      classified as citalopram tolerant were more likely to experience remission (P =
      0.03). No relationship between CYP2D6 genotype-based categories and either
      remission or tolerance was identified, although exploratory analyses identified a
      potential interaction between CYP2C19 and CYP2D6 effects. CONCLUSION: Despite
      several limitations including the lack of serum drug levels, this study showed
      that variations in CYP2C19 were associated with tolerance and remission in a
      large sample of White non-Hispanic patients treated with citalopram.

PMID- 21192346
TI  - Intratympanic steroid therapy for sudden hearing loss: a review of the
      literature.
AB  - OBJECTIVE: Administration of steroids systematically is considered to be the most
      commonly accepted treatment for idiopathic sudden sensorineural hearing loss
      (ISSNHL). In recent years there has been increasing scientific interest in
      treating ISSNHL by means of local steroid delivery. Usually, intratympanic
      steroids are used in three main protocols, as initial treatment, as adjunctive
      treatment given concomitantly with systemic steroids and as salvage treatment
      after failure of standard therapy. The purpose of this review is to examine the
      published literature regarding the therapeutic value of each method of treatment
      and to seek answers about the best delivery technique and the optimal
      administration schedule. DATA SOURCES: Literature review from 1996 to 2009,
      PubMed and Medline. STUDY SELECTION: We searched for trials concerning clinical
      evaluation of intratympanic steroids in ISSNHL patients, as a salvage treatment,
      as a first line therapy and in combination with the conventional therapy.
      Randomized and non-randomized case control studies and case series studies were
      the types of trials available for review. DATA EXTRACTION: All the articles
      described in the study selection were used for this review. DATA SYNTHESIS:
      Statistical techniques were not used. CONCLUSION: On the basis of the available
      literature, it seems that topical steroids can be a valuable solution for ISSNHL
      patients who either cannot tolerate systemic steroid therapy or are refractory to
      it. Concerning the combined therapy, due to the controversial results of the
      existing studies, it cannot be determined yet whether this treatment protocol
      could yield superior results as a first line therapy. The need for establishment
      of standard criteria of hearing recovery should be underlined.

PMID- 21192347
TI  - Evaluation of the round window niche before local drug delivery to the inner ear
      using a new mini-otoscope.

PMID- 21192348
TI  - Verdi is in tune when it comes to blood pressure control.

PMID- 21192349
TI  - Sustained benefits of a health project for middle-aged football supporters, at
      Glasgow Celtic and Glasgow Rangers Football Clubs.

PMID- 21192351
TI  - Pseudohyponatremia in multiple myeloma.

PMID- 21192352
TI  - Keeping the doors open. Recession, reform pave way for Caritas Christi sale.

PMID- 21192353
TI  - Market relief deadline looms. Hospitals, systems look to capitalize while they
      can.

PMID- 21192354
TI  - Payday at HCA. Community Health's loans extended to 2017.

PMID- 21192355
TI  - Time to regulate health IT? AMIA seeks to foment serious consideration of topic.

PMID- 21192356
TI  - Two investors exit PHNS. One system to be shareholder in new owner.

PMID- 21192357
TI  - Kickback claims settled. Maryland case shows feds eyeing physician contracts.

PMID- 21192358
TI  - Both sides need a truce. Hospital administrators, physicians need to team up to
      tackle quality ACOs, IT.

PMID- 21192359
TI  - Quality lessons. Patient-centered care vital to outcomes, cost.

PMID- 21192360
TI  - Workers absorbing costs. Employers say benefit changes on way as healthcare
      expenditures continue to soar.

PMID- 21192361
TI  - Working together. Hospitals, employers each have crucial roles in making reform
      succeed.

PMID- 21192362
TI  - Looking beyond price. Employers can use their buying power to push value-based
      purchasing.

PMID- 21192363
TI  - Breaking down language barriers. Hospital interpreters get credentialed with new
      certification programs.

PMID- 21192364
TI  - Agenda for change. The hurricane of protest over pay can be calmed by honest
      debate.

PMID- 21192365
TI  - Foundations seek to halt automatic pay rises.

PMID- 21192366
TI  - Mark Goldman on process versus outcome.

PMID- 21192367
TI  - John Middleton on public health. Public health needs a long vigil.

PMID- 21192368
TI  - The Capgemini and HSJ Liberating Ideas Award. Make your big idea shine out.

PMID- 21192369
TI  - Commissioning. Keep up the world class commitment.

PMID- 21192370
TI  - Community services. Hit the spot with NHS health checks.

PMID- 21192372
TI  - HSJ100. The people with the greatest influence on health policy and the NHS.

PMID- 21192371
TI  - Politicians and medics surge to power in the new world order.

PMID- 21192373
TI  - beta-trace protein as a diagnostic marker for perilymphatic fluid fistula: a
      prospective controlled pilot study to test a sample collection technique.
AB  - OBJECTIVES: The diagnosis of perilymphatic fluid (PLF) fistula is still
      challenging. Perilymphatic fluid fistula is one possible complication after
      stapedotomy or cochlear implant surgery. We have performed a prospective
      diagnostic pilot study to further investigate beta-trace protein (beta-TP) as a
      marker for PLF fistula. In this pilot study, we tested the sensitivity of the
      beta-TP marker using a simple method for sample collection from the tympanic
      cavity. DESIGN: Prospective controlled diagnostic study. SETTING: Two-center
      tertiary referral hospitals. PATIENTS: A total of 35 adult patients undergoing
      ear surgery were included. Subjects were divided into 2 groups: 1) 19 patients
      undergoing stapedotomy were investigated for PLF fistula in samples obtained from
      the tympanic cavity and 2) 16 patients undergoing myringoplasty were investigated
      for PLF fistula in samples from the tympanic cavity. This group served as the
      control. Mean age +/- SD at surgery was 49.9 +/- 8.0 years in the study group and
      39.69 +/- 15.47 years in the control group. INTERVENTION: beta-Trace protein
      (prostaglandin D synthase) in tympanic cavity samples and serum samples was
      analyzed. The samples were collected by gradually filling the tympanic cavity
      with 100 to 200 MUl sodium chloride and by immediately collecting a volume of 60
      to 100 MUl in a mucus specimen set container. MAIN OUTCOME MEASURES: The
      concentration of beta-TP was quantified using laser nephelometry. RESULTS: The
      median beta-TP in the study group was 0.8 mg/L (range, 0.05-4.5 mg/L). In the
      control group, the median beta-TP value was 0.16 mg/L (range, 0.01-0.36 mg/L).
      Thirty-five percent of the values in the study group were below the highest value
      in the negative control group. The beta-TP values of the tympanic cavity samples
      were significantly higher in the study group than in controls (p = 0.0001). The
      serum values were 0.55 +/- 0.18 and 0.53 +/- 0.11 mg/L, respectively. CONCLUSION:
      It may be feasible to test for PLF fistula using beta-TP in samples from the
      tympanic cavity. Our results, however, suggest a relative low diagnostic
      sensitivity, given a cutoff that is set to obtain a high specificity when using a
      simple sample collection method. Furthermore, the test does not permit the
      distinction between PLF fistula and cerebrospinal fluid fistula. Further studies
      should focus on minimal dilution at sampling and on minimizing sample volumes.

PMID- 21192374
TI  - Hearing results in reconstructing the damaged incus with varying lengths of the
      modified Lippy prosthesis.
AB  - OBJECTIVE: Evaluate success of reconstructing the damaged incus in otosclerotics
      and chronic ear disease with the use of the modified Lippy prosthesis.
      Maintaining ossicular continuity is critical in optimizing sound transfer
      particularly when there has been incus erosion of varying degrees. Our hypothesis
      was that the varying lengths of the Lippy modified prosthesis would allow for
      reconstruction of the incus with very good results. PATIENTS: Clinical records
      were reviewed from 1998 to 2009. Fifty-four patients requiring incus
      reconstruction with the modified Lippy prosthesis were evaluated. INTERVENTION:
      Analysis was done of type of surgery, varying lengths of incus erosion and
      lengths of prostheses used. Audiometric outcomes were evaluated with respect to
      length of prosthesis and type of surgery performed. MAIN OUTCOME MEASURES:
      Audiometric evaluation of 4 frequency closure to within 10 dB air-bone gap (ABG).
      RESULTS: Audiometric results for the 54 patients revealed a mean postoperative
      ABG of 7.8 dB with mean follow-up of 7.4 months. Closure of ABG within 10 dB was
      achieved in 74.1% of patients, and 96.3 % achieved closure within 20 dB. Long
      term follow-up at 51 months for a subset of 15 patients demonstrated a mean
      postoperative ABG of 15.5 dB. No relation was found between prosthesis length and
      ABG at both the initial and long-term postoperative evaluation. CONCLUSION: Incus
      erosion presents a significant challenge in middle ear reconstruction. The
      otologic surgeon must be prepared to perform incus reconstruction whether in
      otosclerosis or in chronic ear surgery. Knowledge in use of the modified Lippy
      prosthesis enables the surgeon to deal with varying degrees of incus necrosis
      yielding very good hearing results.

PMID- 21192375
TI  - Characterization of the electrically evoked compound action potential of the
      vestibular nerve.
AB  - OBJECTIVE: We recorded intraoperative and postoperative electrically evoked
      compound action potentials (ECAPs) in rhesus monkeys implanted with a vestibular
      neurostimulator. The objectives were to correlate the generation of slow-phase
      nystagmus or eye twitches induced by electrical stimulation of the implanted
      semicircular canal with the presence or absence of the vestibular ECAP responses
      and to assess the effectiveness of ECAP monitoring during surgery to guide
      surgical insertion of electrode arrays into the canals. DESIGN: Four rhesus
      monkeys (a total of 7 canals) were implanted with a vestibular neurostimulator
      modified from the Nucleus Freedom cochlear implant. ECAP recordings were obtained
      during surgery or at various intervals after surgery using the Neural Response
      Telemetry feature of the clinical Custom Sound EP software. Eye movements during
      electrical stimulation of individual canals were recorded with a scleral search
      coil system in the same animals. RESULTS: Measurable vestibular ECAPs were
      observed intraoperatively or postoperatively in 3 implanted animals. Robust and
      sustained ECAPs were obtained in 3 monkeys at the test intervals of 0, 7, or
      greater than 100 days after implantation surgery. In all 3 animals, stimulation
      with electrical pulse trains produced measurable eye movements in a direction
      consistent with the vestibulo-ocular reflex from the implanted semicircular
      canal. In contrast, electrically evoked eye movements could not be measured in 3
      of the 7 implanted canals, none of which produced distinct vestibular ECAPs. In 2
      animals, ECAP waveforms were systematically monitored during surgery, and the
      procedure proved crucial to the success of vestibular implantation. CONCLUSION:
      Vestibular ECAPs exhibit similar morphology and growth characteristics to
      cochlear ECAPs from human cochlear implant patients. The ECAP measure is well
      correlated with the functional activation of eye movements by electrical
      stimulation after implantation surgery. The intraoperative ECAP recording
      technique is an efficient tool to guide the placement of electrode array into the
      semicircular canals.

PMID- 21192376
TI  - New, less-invasive technology makes mitral valve repair easier on patients.
      Research shows that many eligible patients opt not to have mitral valve
      procedures out of worries about the surgery, but the risks of delaying treatment
      are serious.

PMID- 21192377
TI  - Get a flu shot and closely monitor your blood pressure this winter.  Cold weather
      tends to raise blood pressure, so be especially careful with outdoor activities,
      and consider a pneumonia vaccine as well.

PMID- 21192378
TI  - Treat sleep-disordered breathing to protect your heart.  Sleep disorders, such as
      obstructive sleep apnea, can put you at risk of high blood pressure, heart attack
      and stroke.

PMID- 21192379
TI  - Curb your sugar intake to lower heart risks.  Cut back on added sugar from
      processed and packaged foods for a slimmer waistline and a healthier
      cardiovascular system.

PMID- 21192380
TI  - "Masked" and "white-coat" hypertension could signal more serious complications.
      Experiencing temporary spikes in blood pressure may put you at greater risk of
      cardiac events.

PMID- 21192381
TI  - If I miss a dose of my statin or blood pressure medication, should I take it as
      soon as I remember it or should I wait until my next scheduled dose to stay on
      schedule?

PMID- 21192382
TI  - Know the 3 main reasons you could benefit from cardiac rehabilitation.  Diet,
      exercise and risk factor reduction are keys to making the most of your recovery.

PMID- 21192383
TI  - Understand your treatment options if you have HOCM. New devices and procedures
      are available to help manage hypertrophic obstructive cardiomyopathy.

PMID- 21192384
TI  - Know the warning signs of worsening PAD.  You may have peripheral arterial
      disease and not even know it.

PMID- 21192385
TI  - I always had very healthy cholesterol levels, but since I went into menopause,
      they have climbed, even though I'm watching my diet more than I ever have.  Is
      this normal and can I do anything about it other than taking medications?

PMID- 21192386
TI  - [Building a bridge from both sides].

PMID- 21192387
TI  - ["This has fully gone by the wayside" - "Not at all"! Coffee discussion on Sunday
      - Peter Hahne chats with Ulla Schmidt about nursing].

PMID- 21192388
TI  - [Unlawful stay: patients need emergency care: "In larger German cities are more
      than 10,000 without legal paperwork (interview by Martina Weber)].

PMID- 21192389
TI  - [Palliative care--needs of patients and nursing staff. "Dying patients sense
      exactly if we are authentic"].

PMID- 21192390
TI  - [Culture sensitive nursing at life's end: a cut up liver or when the soul lies at
      the bottom].

PMID- 21192391
TI  - [Respectful cooperation. Intercultural opening of new nursing facilities].

PMID- 21192392
TI  - [Culture sensitive nursing care in nursing facilities: "Home is where heart and
      soul feel comfortable (Persian proverb].

PMID- 21192393
TI  - [Communication in nursing: interpreters provide trust].

PMID- 21192394
TI  - [Multilingualism and nursing: language as a prerequisite for culture sensitive
      nursing].

PMID- 21192395
TI  - [Specialty periodicals for anesthesia and intensive care: accuracy of reports is
      low - self critical evaluation necessary].

PMID- 21192396
TI  - [Celebrating multicultural Christmas in the nursing home: overcoming boundaries
      with openness].

PMID- 21192397
TI  - [Reorganizing social services in an elder care nursing home: Nursing and
      management from the same hand].

PMID- 21192398
TI  - [Finding a personal role. Occupational identity in the tense relationship between
      nurses and the environment].

PMID- 21192399
TI  - [Carelessly or deliberately? Employee apprehension - organization internal damage
      compensation].

PMID- 21192400
TI  - [From case to case: culture sensitive nursing care].

PMID- 21192401
TI  - [Effects of hypoxia on the proliferation of embryonic stem cells].
AB  - AIM: To investigate the effects of hypoxia on the proliferation of mouse
      embryonic stem cells (mouse ES cells) in vitro. METHODS: We observed the
      proliferation of ES cells by hematometery and BrdU-labeled flow cytometry (FCM),
      and we also detected the expression of hypoxia inducible factor-1a (HIF-1a) by RT
      PCR. RESULTS: (1) The number of ES cells after culturing in the hypoxia
      environment (3% O2 and 10% O2) for 24 hours were lesser than those in normoxia
      (20% O2). (2) The number of ES cells significantly increased after intermittent
      hypoxia (3% O2) stimulus for 10 minutes per day for 4 days. (3) We also observed
      the relation between the expression of HIF-1a and the proliferation of ES cells
      by RT-PCR. The results showed that the expression of HIF-1a had no significant
      change after ES cells were culturing in hypoxia environment (3% O2 and 10% O2)
      for 24 hours or in intermittent hypoxia (3% O2 and 10% O2) for 4 days.
      CONCLUSION: These results suggest that intermittent hypoxia (3% O2) can
      significantly promote the proliferation of ES cells in vitro, while persistent
      hypoxia inhibits those, and the mechanism of these should be addressed in
      further.

PMID- 21192402
TI  - [Effects of acute hypoxia and adenosine on splenic T-lymphocyte proliferation of
      rats].
AB  - AIM: To observe the effects of acute hypoxia and adenosine on splenic T
      lymphocyte proliferation. METHODS: Wistar rats were divided into control and
      hypoxic group, and the latter were exposed to hypoxia (5000 m simulated high
      altitude, 23 h/d). Three days later, spleen cells were collected and stimulated
      by 5.0 microg/ml and 2.5 microg/ml concanavalin A (ConA) to determine the
      splenocyte proliferation. The proliferation was also observed after addition of
      different amount of adenosine to culture medium. RESULTS: Acute hypoxia and
      adenosine had marked inhibitory effect on mitogenic response to Con A in splenic
      T cells, and the inhibitory effect induced by adenosine displayed concentration
      dependent. CONCLUSION: Acute hypoxia may impair the T cell function and adenosine
      could be involved in this process.

PMID- 21192403
TI  - [Effects of GLP-1(7-36)NH2 on insulin secretion and the changes of intracellular
      cAMP and insulin mRNA expression].

PMID- 21192404
TI  - [Effects of chronic intermittent hypoxic exposure on myocardial mitochondria
      ATPase and enzyme complexes of respiratory chain in rats].
AB  - AIM: To study the effects of acute and chronic intermittent hypoxic exposure on
      the activities of Na+ , K+ -ATPase, Ca2 + , Mg2 + -ATPase of myocardial
      mitochondria and enzyme complexes of respiratory chain in rats. METHODS: The
      activities of Na , K+ -ATPase, Ca2+ , Mg2+ -ATPase of myocardial mitochondria and
      enzyme complexes of respiratory chain were investigated after chronic
      intermittent hypoxic exposure (3000 m and 5000 m, 4 h/d, 2 w respectively) and
      normoxic rats were exposed to hypoxia (8000 m) for 4h. RESULTS: (1) Hypoxia had
      no effects on the activity of Na+, K+ -ATPase in myocardial mitochondria of rats.
      (2) Compared with normoxic control rats, the activity of Ca2+, Mg2+ -ATPase in
      myocardial mitochondria of acute hypoxic rats was reduced significantly. After
      chronic intermittent hypoxic exposure, its activity was increased significantly
      compared with that of acute hypoxic rats. (3) Compared with normoxic control
      rats, the activities of enzyme complex I, II and IV of respiratory chain in acute
      hypoxic rats were reduced significantly. After chronic intermittent hypoxic
      exposure, their activities were increased significantly compared with those of
      acute hypoxic rats. Under the same experimental conditions, hypoxia had no
      effects on the activity of enzyme complex III. CONCLUSION: After chronic
      intermittent hypoxic exposure, the activities of Na+, K+ -ATPase, Ca2+, Mg2+ 
      ATPase of myocardial mitochondria and enzyme complexes of respiratory chain were
      increased significantly. These suggested that chronic intermittent hypoxic
      exposure could improve the functions of respiratory chain in myocardial
      mitochondria and keep the normal energy metabolism.

PMID- 21192405
TI  - [Gene expression analysis on human endothelial cells treated by ouabain].

PMID- 21192406
TI  - [Effects of taurine on rabbit cardiomyocyte apoptosis during ischemia/reperfusion
      injury].
AB  - AIM: To study the effect of taurine (Tau) on rabbit cardiomyocyte apoptosis
      during ischemia/reperfusion (I/R) injury. METHODS: Rabbit heart I/R injury was
      induced by occluding the left anterior descending coronary artery for 45 min and
      reperfusion for 180 min. taurine (200 mg/kg) was intravenously injected 5 min
      before heart ischemia. Cardiomyocyte apoptosis was measured by using terminal
      deoxynucleotidyl transferase--mediated dUTP nick end labeling method (TUNEL),
      flow cytometry (FCM) and DNA agarose gel electrophoresis. RESULTS: DNA ladder
      pattern of DNA in myocardium was revealed by agarose gel electrophoresis in I/R
      group while was not found in Tau + I/R group. Apoptotic cardiomyocytes were
      sparse within ischemic myocardium at risk in Tau + I/ R group as compared with
      that in I/R group (TUNEL stain). Apoptosis rate in ischemic myocardium from I/R
      and Tau + I/R groups detected by flow cytometry was 17.66% +/- 1.54% and 4.86% +/
      1.23%, respectively. Fas and Bax protein expressions in ischemic myocardium of
      I/R group were higher than that in nonischemic myocardium group (P < 0.01), Bcl
      2/Bax ratio in I/R group was lower than that in nonischemic myocardium (P <
      0.01); while in Tau + I/R group, Fas and Bax protein expressions were lower than
      that in I/R group (P < 0.01), the Bcl-2/Bax ratio was higher than that in I/R
      group (P < 0.01). CONCLUSION: Taurine reduced apoptosis of myocytes in I/R rabbit
      heart; its mechanism may involve Fas, Bax and Bcl-2 proteins expression.

PMID- 21192407
TI  - [The relationship between the expression of metallothionein-III mRNA and the
      ischemic neuronal damage].

PMID- 21192408
TI  - [The protective effect of taurine on lung injury following limbs
      ischemia/reperfusion of rats].
AB  - AIM: On the model of limb ischemia/reperfusion (LIR), the effects of taurine on
      pulmonary morphological changes in rats were observed. METHODS: Wistar rats were
      divided into three groups (n=8): control group, ischemia/reperfusion group (IR)
      and taurine + IR (Tau + IR). Then macroscopic inspection and optical and
      transmission electron microscopies (TEM) were performed to assess the
      morphological changes of the lung tissues and their lung index (LI) and lung
      permeability index (LPI) and reactive oxygen species (ROS), malondialdehyde (MDA)
      were measured as well. RESULTS: The morphological changes of lung tissue after
      LIR were characterized by an increase of permeability of the alveoli-capillary
      membrane and infiltration of inflammatory cells. Under optical microscopy, there
      were congestion and swelling in pulmonary microvessels with broadened the spaces
      around the blood vessels. Under TEM, a number of tight-junctional regions between
      adjacent alveolar epithelial cells and between pulmonary microvessels endothelium
      were "open". The LI, LPI, MDA and ROS increased. The specimens of Taurine + IR
      group revealed slight to moderate degrees of damages in the lung tissues.
      CONCLUSION: Taurine protects lung from LIR in rats and the protective action on
      tight-junctional regions between cells and anti-oxygen is one of the protective
      mechanisms of taurine.

PMID- 21192410
TI  - [Effects of aerobic calisthenics on composition of the blood fat of young obese
      typed females].

PMID- 21192411
TI  - [Effects of taurine on NOS activity in myocardium and plasma of hemorrhagic shock
      resuscitation in rabbits].
AB  - AIM: To investigate the effect of taurine on nitric oxide synthase (NOS) activity
      and nitric oxide products (NO2 /NO3 ) content in myocardium and plasma during
      shock resuscitation. METHODS: Twenty-four rabbits were divided randomly into 3
      groups (n=8): control group, shock group, taurine group. The model of hemorrhagic
      shock resuscitation was used. The activities of nitric oxide synthase (NOS),
      lactate dehydrogenase (LDH) and the contents of nitric oxide products (NO2- /NO3
      ) in plasma were observed before shock and shock 1.5 hours, after resuscitation 1
      hour, 2 hours and 3 hours. The activities of NOS and the contents of NO2-/NO3- in
      myocardium homogenate were measured after resuscitation 3 hours. Meanwhile,
      pathologic samples treated routinely. RESULTS: (1) During resuscitation, the
      activities of NOS, LDH and the contents of NO2- /NO3- in plasma of shock group
      were significantly higher than that of before shock and shock 1.5 hours (P <
      0.01). (2) After resuscitation 3 hours, the activity of NOS and the contents of
      NO2- / NO3 in myocardium of shock group were significantly higher than that of
      control group (P < 0.01). The cardiac myocyte appeared edema, fatty degeneration.
      (3) All the changes of above mentioned could be attenuated by intravenous
      injection taurine (40 mg/kg) (P < 0.01). CONCLUSION: These results suggest that
      the NOS activation and NO release may mediated myocardium injury induced by shock
      resuscitation, taurine can ameliorate the myocardium injury, which may be related
      to decreasing the generation of NO.

PMID- 21192412
TI  - [Effect of cilostazol on transient outward potassium current in human atrial
      myocytes].
AB  - AIM: To investigate the effect of cilostazol on transient outward potassium
      current (I(to1) in isolated human atrial myocytes. METHODS: Atrial tissue samples
      were obtained from hearts of 15 patients ranging from 5 to 65 years of age (36.0
      +/- 23.9 years). I(to1) was recorded by using the whole-cell patch clamp
      technique in enzymatically isolated atrial myocytes. RESULTS: Cilostazol at 30
      micromol/ L significantly decreased I(to1) at the test potential of +50 mV. The
      peak amplitude of I(to1) was decreased from (8.16 +/- 0.70) pA/pF to (4.84 +/-
      0.60) pA/pF (P < 0.01). In addition, the drug inhibited the current in a
      concentration-dependent manner (IC50 = 13.18 +/- 2.60 micromol/L). The
      significantly inhibitive effect was observed from the concentration of 1
      micromol/L, and the maximal effect was 51.09% +/- 3.0% at 50 micromol/L.
      Furthermore, voltage-dependence of activation and inactivation, and time
      dependent recovery from inactivation of I(to1) were not altered by cilostazol.
      CONCLUSION: The results indicates that cilostazol inhibits I(to1) in human atrial
      myocytes.

PMID- 21192413
TI  - [The influence of acetylcholine on N receptor gamma-subunit of the gastric
      epithelia and the gastric adenocarcinoma cells].

PMID- 21192414
TI  - [Preliminary studies of the mechanism of carbachol increase contraction in rat
      ventricular myocytes].
AB  - AIM: To study whether the mAchR agonist Carbachol(Cch, nonselective) causes
      increased contractions and L-type Ca2+ current [L(Ca(L))] in ventricular myocytes
      and the mechanism of these effects. METHODS: The effect of Cch on the I(Ca(L))
      and Na/Ca exchange current (I(Na/Ca) was studied in patch-clamped ventricular
      myocytes isolated from rat hearts and superfused with Tyrode's solution (35
      degrees C, 1.8 mmol/L [Ca2+]o) and stimulated at 0.2 Hz and 1.0 Hz evoke
      contractions of single myocyte. RESULTS: (1) An increase of stimulation frequency
      decreased the contractions of myocytes(negative inotropic effects). (2) 100
      micromol/L Cch increased contraction in 6 cells by 28% (delta L0.2 Hz/ delta L1.0
      Hz > or = 1.25) at 1.0 Hz stimulus frequency. (3) The mAchR antagonist Atropine
      prevented the Cch effect. The mAchR agonist McN-A-343 (M1-selective) did not
      change the contractions in most of the cells. (4) 100 micromol/L Cch had no
      significant effect on basal I(Ca(L)), but increased the tail current density on
      repolarization from +10 mV to -40 mV, suggested that Cch increased I(Na/Ca).
      CONCLUSION: The increase of cell contractions by Cch is apparently mediated by M2
      mAchR and eventually increased I(Na/Ca). The increase Ca2+ content of the SR is
      reflected by the greater magnitude of I(Na/Ca). These results provide an
      explanation for the increased contraction of the rat ventricular myocytes by Cch
      and without changes in I(Ca(L)).

PMID- 21192415
TI  - [A exploration of relationship between I/D polymorphism of ACE gene and human
      sensibility and plasticity to navigation-motion-sickness].

PMID- 21192416
TI  - [Myocardial free radical metabolic changes in rats after repeated high +Gz
      exposure and protective effects of low-G preconditioning and tea polyphenols].
AB  - AIM: To determine whether repetitive exposure to high sustained +Gz acceleration
      induces persisting changes in the myocardial free radical metabolism and observe
      the protective effects of low-G training and antioxidant tea polyphenols (TP).
      METHODS: Thirty-two male Wistar rats were randomly divided into four groups (n=8
      each): group A, restrained, was only submitted to +1 Gz for 5 min. Group B,
      centrifuged, was exposed to five plateaus of 30 s at +10 Gz for intermittent
      times, three times a week, for three weeks. Group C, low-G trained, was exposed
      to +2 Gz for 5 min about 1 h prior to +10 Gz stress, and group D was orally given
      TP at dose of 200 mg/kg about 1 h prior to +10 Gz stress. On the next day morning
      after last centrifuge run, the rats were decapitated and the hearts were quickly
      removed. Malondialdehyde (MDA) concentration and superoxide dismutase (SOD)
      activity were measured. Additionally, CuZn-SOD and inducible NO synthase (iNOS)
      enzymatic contents were examined by immunohistochemical staining and their mRNA
      were analyzed by semi-quantitative reverse transcription polymerase chain
      reaction(RT-PCR). RESULTS: Compared with group A, MDA concentration and iNOS
      enzymatic content in myocardial mitochondria were increased significantly (P <
      0.05) in group B. Compared with group B, mitochondrial SOD activity was
      significantly increased in group C (P < 0.05). iNOS enzymatic content was
      significantly decreased in group C and D. There were no significant differences
      of CuZn-SOD content, CuZn-SOD and iNOS mRNA levels among the four groups.
      CONCLUSION: Repeated high +Gz exposure can induce myocardial free radical
      metabolic disorder and mainly result in mitochondrial peroxidative injury. But
      low-G training and natural antioxidant TP have protective effects, and the former
      is better.

PMID- 21192417
TI  - [Change of heme oxygenase-1 mRNA in the ischemic preconditioning of isolated rat
      heart].

PMID- 21192418
TI  - [Noradrenaline is involved in cardiovascular responses induced by
      intracerebroventricular injection substance P in rabbits].
AB  - AIM: To investigate the role of intracerebroventricular (icv) injection substance
      P(SP) in cardiovascular regulation and the relationship with noradrenergic
      system. METHODS: Rabbits anesthetized with urethane were
      intracerebroventricularly given SP in presence or absence of phentolamine,
      prazosin, yohimbine. Cardiovascular responses including heart rate (HR), mean
      arterial blood pressure (MAP), left ventricular systolic pressure (LVSP), left
      ventricular end diastolic pressure (LVEDP), the maximum velocity of ascending or
      descending in intraventricular pressure (+/- dp/dt(max)) and the maximum
      shortening velocity(Vpm) of myocardial contractile element were recorded, and
      changes of NA content in cerebrospinal fluid (CSF) were determined in rabbits
      with icy injection of SP. RESULTS: (1) icv SP elicited significant increased of
      HR, MAP, LVSP, LVEDP, + dp/dt(max), -dp/dt(max), Vpm and the levels of NA in
      intracisternal CSF 30 min after injection. (2) Pretreatment with phentolamine,
      prazosin, but not yohimbine, attenuated icv SP-induced cardiovascular responses
      compared with controls (P < 0.05). CONCLUSION: (1) icv SP can produce positive
      inotropic and chronic response in myocardium and pressor response in intact
      rabbits. (2) alpha1 adrenoceptors may be involved in the cardiovascular responses
      to icy SP. (3) Central administration of SP can increase the release of NA or
      inhibit reuptake of NA, which may be responsible for an important mechanism of SP
      potentiated cardiovascular responses in brain.

PMID- 21192419
TI  - [Effect of IGF-1 on PI3K/PTEN signal pathway in vascular smooth muscle cell].
AB  - AIM: To investigate the cellular signal transduction pathway of vascular smooth
      muscle cell (VSMC) proliferation stimulated by insulin-like growth factor-1 (IGF
      1). METHODS: Rabbit aortic VSMCs was cultured in 3 groups. Cell proliferating
      ability was determined by measuring cell number and mitochondrial dehydrogenase
      (MD) activity (MTT assay). Wortmannin (WT), the specific inhibitor of
      phosphatidylinositol 3-kinase (PI3K), was used to evaluate indirectly the
      possible involvement of PI3K. Western blotting was used to detect the protein
      expression of phosphatase PTEN. Diphosphate action of PTEN on its specific
      substrate diC16PIP3 was measured by green reagent method. RESULTS: IGF-1 (100
      microg/L) increased cell number and MD activity by 2.8-3.8 fold. WT markedly
      inhibited VSMC proliferation and completely abolished the above effects of IGF-1.
      IGF-1 inhibited PTEN activity in a concentration-(10-100 microg/L) and time--(3
      min-24 h) dependent manner (P < 0.01). CONCLUSION: IGF-1 increases VSM
      proliferation by increasing PI3K activity and inhibiting PTEN activity.

PMID- 21192420
TI  - [Effect on hyperplasia of VSMCS in rat by the plasmid containing the short
      hairpin RNA of AT1R].
AB  - AIM: RNA interference is a new technology that inhibit effectively of the
      expression the specific genes. The present study was designed to investigate
      whether the plasmid containing the short hairpin RNA (shRNA) of angiotensin II
      type 1 receptor (AT1R) can inhibit the hyperplasia of VSMCs in rat. METHODS: The
      plasmids containing the shRNA of AT1R were constructed, and transfected vascular
      smooth muscle cell (VSMC) to detect the effect on the AT1R expression by RT-PCR
      and Western blot, and detect the hyperplasia of VSMCs by trypan blues training
      and MTT. RESULTS: The plasmids was certified to be in the right rank, and there
      was significant difference (P < 0.01) in the expression of AT1R mRNA and protein
      between the plasmid transfected group and the control group. There was
      significant difference (P < 0.01) in the hyperplasia of VSMCs between the plasmid
      transfected adding Ang II group and the control group. CONCLUSION: The plasmids
      containing the shRNA of AT1R have the effect of RNAi, and inhibit the hyperplasia
      of VSMCs induced by Ang II in rat.

PMID- 21192421
TI  - [Function of endothelin-1 in neurogenic pulmonary edema].
AB  - AIM: To investigate the role of endothelin-1 in the pathogenesis of neurogenetic
      pulmonary edema. METHODS: The levels of endothelin-1 in plasma and lung were
      measured in rats which suffered from diffuse brain injury on Marmarous' model.
      The changes of endothelin-1 in the lungs were also detected using an
      immunohistochemical method. RESULTS: After heavy diffuse brain injury in rats,
      the levels of endothelin-1 in plasma and lung began increasing at 1 hour, and
      peaked at 6 hour. Though a little declining at 24 hour, it maintained a higher
      level within 48 hours (P < 0.05). Pulmonary pathology showed that after brain
      injury there were congestion, swelling in pulmonary microvessels with broadened
      pulmonary interstitial tissue, and leucocyte infiltration was dominated by
      neutrophils and monocytes from 1 hour on, which peaked at 6 hour. More serious
      congestion, swelling and protein effusion in pulmonary alveoli were observed at
      both 24 h and 48 h. Immunohistochemically, endothelin-1 had more significant
      expression and higher levels of OD in the experimental groups than that in the
      control's, the most significance of which was at 6 hour. CONCLUSION: The
      inflammatory injury mechanism caused by endothelin-1 may play an important role
      in neurogenic pulmonary edema.

PMID- 21192422
TI  - [Screening differentially expressed genes in the process of vascular smooth
      muscle cell calcification in vitro].
AB  - AIM: The process of vascular calcification involves various genetic alterations
      which may play a very important role in the vascular calcification. Vascular
      smooth muscle cells undoubtedly composed the main part of vascular cells, and are
      involved in vascular calcification. So bovine artery smooth muscle cell (BASMC)
      was used to investigate the gene changes during BASMC's calcification. METHODS:
      Bovine artery smooth muscle cells cultured in vitro was induced calcified by beta
      Glycerophosphate (beta-GP). Using DD-PCR technique to screening differentially
      expressed genes and those differentially expressed bands were reexamined by
      reverse Northern blot. All the ESTs were sequenced and BLAST with GenBank.
      RESULTS: Total 65 cDNAs were isolated as differentially expressed genes and 40 of
      them were successfully reamplified. Using reverse-Northern blot, seven of these
      40 cDNAs were reproducibly expressed differentially between the two cells. Three
      of them are new bands and have not been reported before. CONCLUSION: This is the
      first time using DD-PCR to screen differentially expressed genes of BASMC
      calcification. Seven related ESTs were identified relating to BASMC
      calcification.

PMID- 21192423
TI  - [Effects of the central amygdaloid nucleus lesions on tastants intake in rats].
AB  - AIM: To investigate the effects of central amygdaloid nucleus (CeA) on the
      evaluation of taste in rats, and explore the mechanisms of the CeA in modulating
      the feeding behavior. METHODS: By using two-bottle choice test, we measured the
      consumption of serials concentrations of NaCl, citric acid (CA), quinine HCl
      (QHCl) and sucrose in bilateral CeA lesioned rats, and compared the results to
      those in sham lesioned rats. RESULTS: The CeA-lesioned rats exhibited a lower
      preference for NaCl at concentrations of 0.03; 0.1 and 0.3 mol/L, for CA at
      concentrations of 0.01; 0.1 and 1.0 mmol/L, and for QHCl at 10; 20 and 50
      micromol/L, but the preference for serials of concentrations of sucrose are
      similar between two groups. By comparing the intake of adjacent concentrations of
      sapid solutions, it indicated that CeA-lesioned rats showed a lower distinction
      between adjacent concentrations of NaCl, CA and QHCl. However, the total
      consumption (water and tastants) during all the test sessions was not
      significantly different between two groups of rats. CONCLUSION: Lesion of CeA
      decreases the intake of tastants solution, but the effects on different
      concentrations of solution are different. It suggests that the CeA plays an
      important role in the normal response to exteroceptive food stimuli through
      impacting on the assessment of taste and altering the preference threshold of
      gustatory stimuli.

PMID- 21192424
TI  - [Differentiation of human fetal liver CD34+ cells into neuronal cells induced by
      beta-ME and BHA in vitro].
AB  - AIM: To establish model of differentiation of fetal liver stem cells induced by
      beta-ME + BHA into neural cells in vitro; METHODS: CD34+ cells from naturally
      aborted human fetal liver were isolated with MACS Kit, and cultured in Dulbecco's
      modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS).
      After confluent more than 80%, the 5 passage cells were induced by 10(-3) mol/L
      beta-mercaptoethanol (beta-ME) and 2 x 10(-4) mol/L BHA for 24 hours, and washed
      with PBS, and then incubated in serum-free medium for 5 hours to 5 days. The
      characteristics of treated cells were assayed by immunocytochemistry staining
      analysis. RESULTS: Cells treated by beta-ME+ BHA exhibited neuronal phenotype,
      and expressed neuronal specific proteins such as nestin, NeuN, TrnJ-1, and NF-M,
      which were not found in control cells. Statistic analysis showed that 81% cells
      were NeuN-positive, 75% cells TuJ-1-positive, 47% cells NF-M-positive, 90% cells
      NSE-positive. CONCLUSION: beta-ME + BHA can induce human fetal liver CD34+ cells
      to produce neuronal specific antigens and proteins in vitro and become neuronal
      cells. CD34+ cells from human fetal liver possess potentials of differentiation
      into neural cells.

PMID- 21192425
TI  - [Assessment of the effect of oxygen supply in liquid-oxygen at high altitude].

PMID- 21192426
TI  - [Histaminergic receptor in the NTS involved in inhibition of carotid baroreflex
      induced by intracerebroventricular injection of HA in rats].
AB  - AIM: To explore the role of histaminergic receptors in the nucleus tractus
      solitarius (NTS) in the responses of carotid baroreflex (CBR) performance to the
      intracerebroventricular (ICV) injection of histamine (HA). METHODS: The left and
      right carotid sinus regions were isolated from the systemic circulation in 18
      Wistar rats anesthetized with pentobarbital sodium. The intracarotid sinus
      pressure (ISP) was altered in a stepwise manner. ISP-mean arterial pressure (MAP)
      relationship curve and its characteristic parameters were constructed by fitting
      to the logistic function with five parameters. We observed the changes in CBR
      performance induced by ICV HA and the effects of pretreatment with HA receptors
      antagonists into the NTS on the responses of CBR to HA. RESULTS: ICV injection of
      HA (100 ng) significantly shifted the ISP-MAP relationship curve upwards and
      moved the middle part of ISP Gain relationship curve downwards, and reduced the
      MAP range and maximum gain (Gmax), but increased the threshold pressure (TP),
      saturation pressure(SP) and ISP at Gmax (ISP(Gmax)). The pretreatment with H1 or
      H2 receptors antagonist, chlorpheniramine (CHL, 0.5 microg) or cimetidine (CIM,
      1.5 microg) into the NTS, could obviously diminish the above-mentioned changes in
      CBR performance induced by HA, but the effect of CIM was less remarkable than
      that of CHL. CONCLUSION: The intracerebroventricular administration of HA results
      in a rapid resetting of CBR and a decrease in reflex sensitivity, and the
      histaminergic receptors in the NTS (H1 and H2 receptors), especially H1 receptors
      might play an important role in the responses of CBR to HA, and furthermore, the
      effects of the central HA on CBR might be related to a histaminergic descending
      pathway from the hypothalamus to NTS.

PMID- 21192427
TI  - [Efficacy of zishen prescription on the learning and memory-abilities of aging
      model rats].

PMID- 21192429
TI  - [Changes of COX-2 expression in the dorsal horn of the spinal cord during
      formalin-induced inflammatory pain and hyperalgesia in rats].
AB  - AIM: To observe the changes of cyclooxygenase-2 (COX-2) expression and especially
      the time course of the changes in dorsal horn of the spinal cord during formalin
      induced inflammatory pain and hyperalgesia in rats. METHODS: COX-2
      immunohistochemistry staining was used in rat formalin pain model. RESULTS:
      Compared with control group the number and immunostaining density of COX-2
      immunoreactive cells in the laminae I-VI of the dorsal horn of the spinal cord
      increased significantly 4 h, 1 d and 3 d after formalin injection (P < 0.05). The
      most obvious increase was observed 1 d after the injection. CONCLUSION: COX-2 in
      the dorsal horn of the spinal cord is involved in the formalin-induced
      inflammatory pain and hyperalgesia.

PMID- 21192428
TI  - [Effect of CGRP receptor antagonist CGRP8-37 on nociceptive response, NOS
      expression and NO content in the dorsal horn of spinal cord during formalin
      induced inflammatory pain in rats].
AB  - AIM: To study the effect of CGRP receptor antagonist CGRP8-37 on nociceptive
      response and expression of nitric oxide synthase (NOS) and content of nitric
      oxide (NO) in the dorsal horn of the spinal cord of rats during formalin-induced
      inflammatory pain. METHODS: Using formalin injection into right hind paw induced
      inflammatory pain. Counting the times of flinching reflex was used to observe the
      degree of spontaneous pain. NADPH-d histochemistry was used to observe the
      changes of NOS expression. The content of NO was observed by measuring the
      contents of nitrate/nitrite (NO3- / NO2-). RESULTS: spontaneous pain behavioral
      was elicited by formalin injection. The NOS expression and NO content
      significantly increased in the spinal cord at 24 h after formalin injection.
      Intrathecal injection of CGRP8-37 could significantly inhibit the response of
      spontaneous pain and the increases of NOS expression and NO content induced by
      formalin injection. CONCLUSION: The activation of CGRP receptors enhances NOS
      expression and NO production in the dorsal horn of the spinal cord during
      formalin-induced inflammatory pain.

PMID- 21192430
TI  - [Effect of bombesin on IFN-induced fever and AVP content in brain of rats].
AB  - AIM: To determine whether bombesin prevents IFN-alpha-induced fever and it's
      possible mechanism. METHODS: Effects of BN on changes in body temperature and
      arginine vasopressin(AVP) content in the ventral septal area(VSA) and
      hypothalamus were measured in the rats following intracerebroventricular (ICV)
      injection of IFN-alpha. RESULTS: (1) IFN-alpha produced a dose-dependent rise in
      colonic temperature simultaneously with increase in AVP content in the VSA in the
      rats. (2) BN produced a dose-dependent hypothermia and significantly elevated AVP
      content in the VSA in rats. (3) BN injected intracerebroventricularly at 30 min
      after IFN-alpha prevented the increase in colonic temperature which recovered to
      the control level as well as AVP content in the VSA in rats at 150 min.
      CONCLUSION: AVP in the VSA may play a role in IFN-alpha-induced fever. AVP in the
      VSA may play a partial role in the BN antipyretic action and hypothermic action.

PMID- 21192431
TI  - [Changes of contents of extracellular signal-regulated kinase in rat hepatic
      fibrogenesis induced by bile duct ligation].
AB  - AIM: To observe the dynamic expression of ERK1 in fibrotic rat liver. METHODS:
      The rat hepatic fibrosis was induced by bile duct ligation (BDL).
      Histopathological changes were evaluated by hematoxylin and eosin staining, and
      by Masson's trichrome method. ERK1 mRNA in liver was determined by reverse
      transcription-polymerase chain reaction (RT-PCR), while the distribution of ERK1
      was assessed by immunohistochemistry. ERK1 protein was detected by using Western
      blotting analysis. RESULTS: With the development of hepatic fibrosis, the
      positive cells of ERK1 increased a lot, they were mainly distributed at portal
      ducts, fiber septa and around the bile ducts, vascular endothelial cells and
      perisinusoidal cells. Western blotting analysis results displayed that the
      expression of ERK1 protein were up-regulated with model course, and its levels
      were the highest at week 4 after operation, achieving to 3.9-fold of that in
      normal rat liver. ERK1 mRNA expressed in normal rat livers as well, they were up
      regulated at day 2 after BDL and its level was the highest at week 4 after BDL.
      CONCLUSION: These data suggest that the expression of ERK1 and its mRNA can be
      increase greatly in fibrotic rat liver.

PMID- 21192432
TI  - [Study of the transmission route of epileptiform discharges in amygdaloid
      kindling model].

PMID- 21192433
TI  - [The method of monitoring sleep state and respiratory rhythm in freely moving
      rats].
AB  - AIM: To devise a new method for testing the animal model of sleep apnea syndrome
      (SAS). METHODS: We simultaneously monitoring the respiratory wave through a micro
      pressure transducer and the electrical signals of both electrocorticogram (ECoG)
      and electromyogram (EMG), for detecting the sleep-wake states and the respiratory
      rhythm in rats. The recording data are analyzed by the manual-computer work.
      RESULTS: The ECoG and EMG signals are stable and easily to distinguish. We can
      accurately detect the sleep-wake state and the sleep apnea events in rats by
      these signals. CONCLUSION: The method is reliable to test the small animal model
      of SAS, and is easily to operate.

PMID- 21192434
TI  - [Research in the field of cell therapy as the object of administrative
      intervention. What has to be done to conduct research in Spain with embryonic
      stem cells?].
AB  - The intervention of the government in the field of research in cell therapy is a
      reality in all countries of our environment. Such intervention is determined by
      many factors. We can emphasize the protection of the human live and the safety of
      person. Spain is not an exception to this. There has long been a legal and
      organizational system that trying to address the multiple problems raised in the
      field of the biomedicine. This article analyses the scope of such intervention.

PMID- 21192435
TI  - [Chakrabarty today: 30 years after the United States Supreme Court Resolution].
AB  - The decision of the United States Supreme Court in the Chakrabarty case marked
      the beginning of a far reaching process, the development of which considerably
      extended the field of patentabiltiy of humans, their body parts and genetic
      information. The author believes that a period of three decades is sufficient to
      draw conclusions. A critical point has been reached from a debatable decision,
      which had more economic support than legal, which requires serious recapitulation
      of the scope and the purpose of industrial property rights.

PMID- 21192436
TI  - [Genetics as a relevant factor for the purpose of judging criminal imputability.
      Status of the issue and critical perspective. Considering particularly the
      Decision of the Trieste Court of Appeals (Italy) of September 18, 2009].
AB  - The present contribution analyses the relevance of the genetic predispositions in
      the field of Criminal Law. Its principal effect is basically associated with the
      sphere of the Insanity Defense, due to the fact that a number of psychiatric
      alterations or abnormalities relevant for the Insanity Defense show a genetic
      basis. This statement has been recently confirmed by new scientific evidences and
      in the judicial framework by the Sentence of the Court of Appeal of Trieste
      (Italy) from 18th September 2009 which accepts the genetic characteristics of the
      defendant as a relevant data in order to cut the sentence given to a person
      convicted of murder.

PMID- 21192437
TI  - [Tort liability in the application of assisted reproduction techniques:
      differences with biomedical research (Regarding the SSTS of October 23, 2008 and
      November 20, 2009)].
AB  - The first court decisions concerning tort liability in assisted reproduction
      treatments have started to be enacted in Spanish law. They emphasize the scope of
      the health professionals' duty to inform more thoroughly in this field, than on
      curative medicine. This article discusses the basis of the liability in
      reproductive medicine in the light of art. 18 of Law 14/2006 of 26 May, and the
      notable differences in compensation for damage aroused in biomedical research,
      which is governed by a particular system established by Law 14/2007 of 3 July.

PMID- 21192438
TI  - [Ethical aspects of neonatal genetic screening].
AB  - The expansion of newborn genetic screening programs modifies the basic ethical
      criterion which has justified these interventions: the early detection to provide
      a treatment or a clinical benefit to the child. By including diseases in which
      the relationship between benefit and damage is less clear, some questions arise,
      such as anxiety of parents for false positives, the type of information and
      advice that should be provided, if these data really represent an improvement,
      the possibility of demanding an informed consent, and if the long-term costs are
      properly compensated, not only in economic terms but also in quality of life.

PMID- 21192439
TI  - [Type Code of the pharmaceutical industry for the protection of personal data in
      the field of clinical research and pharmaceutical surveillance].
AB  - The Type Code establishes uniform criteria in the sectoral application of the
      Organic Law on Data Protection (LOPD) and its implementing Regulation increases
      the guarantee of its compliance and reduces the level of uncertainty as to its
      implementation. Two key activities in the pharmaceutical industry are considered,
      namely clinical research and pharmacovigilance, all scenarios that take place in
      the daily practice of these activities are developed and procedures for the use
      of personal data and irreversible dissociation are established, with these last
      being exempt from the application of data protection legislation. It develops a
      protocol that includes the guidelines to follow with regard to the exercise of
      rights of access, rectification, cancellation and opposition exercised by those
      affected and stipulates the supervisory functions of the Code by the Monitoring
      Committee.

PMID- 21192440
TI  - [Royal Decree 42/2010, of January 15, regulating the National Commission on Human
      Assisted Reproduction].

PMID- 21192441
TI  - [Older people, a new risk group on the horizon].

PMID- 21192442
TI  - [Fungal diseases of vulva and vagina caused by Candida species].
AB  - Fungal diseases of vulva and vagina attributed to Candida species (vulvovaginal
      candidosis) are the most frequent mycoses of women. They show acute or chronic
      courses and different disease patterns which can strongly affect the quality of
      life of the women who are concerned. In general, the most common cause of acute
      vulvovaginal candidosis is Candida albicans, followed by C. glabrata. In chronic
      recurrent vulvovaginal candidosis, C. albicans and C. glabrata are often equally
      distributed. In several cases, treatment requires an antimycotic therapy which
      refers to the severity and main form of disease as well as to the aetiological
      agent. Most vulvovaginal candidoses are accessible to the treatment with local
      and systemic antimycotic agents. Generally, in Germany azoles such as
      clotrimazole, fluconazole and itraconazole, the polyens nystatin and Amphotericin
      B and the hydroxypyridone derivative ciclopirox are available for antimycotic
      therapy of vulvovaginal candidoses. Significance of non-conventional and adjuvant
      therapeutic approaches is considered to be generally low.

PMID- 21192443
TI  - [Prion safety of medicinal products using the example of an influenza vaccine
      produced in a cell line].
AB  - Prions are pathogenic proteins and are the cause for spongiform encephalopathies.
      Pathogenic prions differ from physiologically common non-pathogenic prions only
      in their sterical structure. Upon infection by a pathogenic prion protein, a
      series of reactions is initiated in which common non-pathogenic prion proteins
      are transformed into pathogenic prions. Animals, mainly ruminants like cattle,
      sheep and goats are susceptible to prions, but also man. Prions are very robust
      and it is difficult to inactivate them. During the production processes of
      pharmaceuticals, the risk for contamination by infectious prions can be reduced
      by careful choice of animal material, the replacement of animal material and by
      appropriate production procedures. For instance biologicals like influenza
      vaccines can be produced by a permanent canine cell line, whose prion safety has
      been proven by useful methods (standard scrapy cell assay). Mandatory guidelines
      ensure that the risk for contamination by pathogenic prions has to be considered
      and excluded in the production of bio-pharmaceuticals.

PMID- 21192444
TI  - [Medication a patient with late infection of total knee endoprosthesis].

PMID- 21192445
TI  - [High dose of simvastatin to minimize the risk of myopathy?].

PMID- 21192446
TI  - [A very severe case. Penis disappeared].

PMID- 21192447
TI  - [Naturopathy consultation. Atopic dermatitis].

PMID- 21192448
TI  - [Urine test strips: diagnostic jack of all trades].

PMID- 21192449
TI  - [Proteinuria].

PMID- 21192450
TI  - [Incidental finding: elevated serum creatinine].

PMID- 21192451
TI  - [Elevated liver enzymes].

PMID- 21192452
TI  - [Hypertension in children and adolescents].

PMID- 21192453
TI  - [Rivastigmine patch effective for 24 hours. Effective dose, good tolerance,
      reliable therapeutic effectiveness].

PMID- 21192454
TI  - [Rupture of the extensor tendons--a possible complication following fracture of
      the distal radius].

PMID- 21192455
TI  - ["My child cannot sleep at night"].

PMID- 21192456
TI  - [Fingers of Hippocrates. Show me your hands!].

PMID- 21192457
TI  - [Interview with public health minister Dr. Phillip Rosler. "I want to strengthen
      ambulatory medical care" (interview by Thomas Hommel and Wolfgang van den Berg)].

PMID- 21192458
TI  - [Individual parenteral nutrition. Prescription when it is medically necessary].

PMID- 21192459
TI  - [Naturopathy consultation. Mucositis of the mouth and throat].

PMID- 21192460
TI  - [Incidental finding with oncological relevance? How much diagnostic is
      necessary?].

PMID- 21192461
TI  - [Swollen lymph node: infectious disease or malignancy].

PMID- 21192462
TI  - [Leukocytopenia].

PMID- 21192463
TI  - [Unexpected peaks in serum electrophoresis].

PMID- 21192464
TI  - [Hypercalcemia].

PMID- 21192465
TI  - [Mild cognitive impairment in the elderly].

PMID- 21192466
TI  - [Increased risk of cancer using insulin and insulin analogues?].

PMID- 21192467
TI  - [Peripheral and central vascular catheter as risk for primary nosocomial sepsis
      in premature infants].

PMID- 21192468
TI  - [Chickenpox and herpes zoster - 2 disease pictures, a single pathogen].

PMID- 21192469
TI  - [Heart valves].

PMID- 21192470
TI  - [Children who coming from all over. Is Mehmet healthier than Matthias?].

PMID- 21192471
TI  - [Caution in food preparation: our body needs iodized salt!].

PMID- 21192472
TI  - [Specialized ambulatory pediatric palliative care (SAPPV) - a concept for
      implementing comprehensive care in Lower Saxony].

PMID- 21192473
TI  - [Palliative care at the end of life: which medical measures are evidence based?].

PMID- 21192474
TI  - [Pure joy of life - despite handicap. In Frankfurt the "8th German Down Syndrome
      Sports Festival" has started].

PMID- 21192475
TI  - [Family is always welcome - nursing foundation praises pediatric intensive care
      unit].

PMID- 21192476
TI  - [Genetic diagnosis regulation of 2009 endangers newborn infants massively.
      Collaborative explanation of the Child Network e. V. and German Society of Social
      Pediatrics and Youth Medicine].

PMID- 21192477
TI  - [Interview about "every child is a gift" (interview by Angelika Staub)].

PMID- 21192478
TI  - [Insurance medicine continuing education of the German Society of Insurance
      Science - interesting and practice relevant].

PMID- 21192480
TI  - [Evidence-based expert testimonies on psychiatric disorders--risk factors for
      invalidity].
AB  - Psychiatric symptoms often lead to a claim for disability pension. Surprisingly,
      there is very little empirical data available on which variables may predict
      permanent job disability. A new empirically based risk assessment instrument was
      developed to predict the final pension outcome. This study used prospective data
      over a 4-year period to examine the variables of the assessment instrument and
      the final outcome. Data of 223 subjects with psychiatric complaints were assessed
      at the time of evaluation for an invalidity pension claim. 95 (42.6%) of them
      were without a reduction of capability, 128 (57.4%) had a reduction of
      capability. Eight variables assessed at the initial psychiatric evaluation
      correlated significantly with the subsequent expert testimony. After applying a
      logistic regression (maximum likelihood estimation) we found 2 variables assessed
      at the initial psychiatric evaluation which correlated significantly with the
      expert testimony. These variables were the resumption of social activities and
      self-estimation of the subject's health and capability. The proportion of
      response variation explained by the regressors (Nagelkerkes R2) was 22%. Further
      research should aim to differentiate subjects with "high risks" from those with a
      better prognosis, with respect to future disability pensioning. One major task
      facing disability adjudicators is to separate those who have a legitimate
      disability claim from those who should be recommended for more intensive
      treatment modalities in order to successfully prevent permanent job disability.

PMID- 21192479
TI  - [Symptom validity tests in psychiatric assessment: a critical review].
AB  - Neuropsychological symptom validity testing is increasingly used even in
      psychiatric expert assessment. Low scores on symptom validity tests can only
      demonstrate exaggerated symptoms. However, symptom validity tests do not address
      the question of whether the result is intentionally produced or motivated by
      internal incentives. Therefore, symptom validity tests cannot differentiate
      between malingering and somatoform disorder. Test results have to be considered
      carefully in the medicolegal context and require thorough clinical assessment.

PMID- 21192481
TI  - [Appraisal of somatoform disorders (II)].

PMID- 21192483
TI  - [Indication criteria for stationary psychosomatic treatment (III)].

PMID- 21192482
TI  - [Therapy options in the case of advanced therapy resistant Morbus Parkinson].
AB  - In Germany about 300,000 to 400,000 people are suffering from Morbus Parkinson at
      present. It is one of the most common neurological diseases both in Germany and
      in Europe as a whole. With the rising number of elderly people in our population,
      the number of Parkinson patients will strongly increase as well in future. About
      20% of these patients are already in an advanced stage. This stage leaves its
      marks with motor and non-motor sequelae. With the minority of these patients oral
      medication is ineffective. For these relatively rare cases an indication for an L
      dopa-infusion therapy (duodopa pump), an apomorphine pump therapy or a deep brain
      stimulation may exist. The indication for one of these 3 therapy forms is given
      by the neurological clinic in agreement with the patient and is only given in
      case of failure of oral medication. All 3 therapy options are very expensive. In
      case of the deep brain stimulation, close cooperation between the neurologist and
      the neurosurgeon as well as with the patient is necessary. Experts warn about a
      transplantation of stem cells because there are no clinical studies and only
      partial clinical improvement with severe side effects are known. The
      transplantation of stem cells for advanced Morbus Parkinson is not a medically
      necessary treatment at present.

PMID- 21192484
TI  - [MRSA--current aspects of resistance, pathology, epidemiology and therapy].
AB  - The Methicillin-resistant Staphylococcus aureus (MRSA) is a Staphylococcus aureus
      (S. aureus) resistant against all kinds of beta-lactam antibiotics. Moreover,
      resistances against other antibiotics have gradually started to develop. In the
      last decades, MRSA started as a serious problem only in hospitals, but in recent
      years it also rose as an alarming community pathogen. In addition to the
      resistances against Penicillin which emerged in the 1940s. with the use of beta
      lactamase proof antibiotics in the 1960s, the resistance of S. aureus against
      Methicillin started to develop. According to the kind of resistance, the
      genotype, the time of infection and the origin of the infection, MRSA infections
      are classified as hospital-associated (HA-MRSA) and community-associated (cMRSA).
      On the one hand, this differentiation results in distinct strategies of
      calculated therapy against each class of MRSA. On the other hand, it is important
      in order to identify relevant judicious aspects of transmission.

PMID- 21192485
TI  - Proceedings of the 2009 Hamburger Hamophilie Symposium.

PMID- 21192486
TI  - [Q & A. A case showing notable accumulation of FDG in the stomach in PET
      following surgery of lung cancer].

PMID- 21192487
TI  - Physician ownership of medical equipment.
AB  - This Data Bulletin presents findings from the Center for Studying Health System
      Change (HSC) 2008 Health Tracking Physician Survey, a nationally rep-resentative
      mail survey of U.S. physicians providing at least 20 hours per week of direct
      patient care. The sample of physicians was drawn from the American Medical
      Association master file and included active, nonfederal, office- and hospital
      based physicians. Residents and fellows were excluded, as well as radiologists,
      anesthesiologists and pathologists. The survey includes responses from more than
      4,700 phy-sicians, and the response rate was 62 percent. Since this Data Bulletin
      examines the extent of physician practice ownership or leasing of medical
      equipment, the sample was limited to 2,750 physicians practic-ing in community
      based, physician-owned practices, who represent 58 percent of all physicians
      surveyed. Physicians employed by hospitals, who practiced in hospital-based
      settings or who worked in hospital-owned practices were excluded.

PMID- 21192488
TI  - Self-insurance and the potential effects of health reform on the small-group
      market.
AB  - The Patient Protection and Affordable Care Act (PPACA) as amended by the Health
      Care Education Reconciliation Act of 2010 makes landmark changes to health
      insurance markets. Individual and small-group insurance plans and markets will
      see the biggest changes, but PPACA also affects large employer and self-insured
      plans by imposing rules for benefit design and health plan practices. Over half
      of workers--most often those in very large firms--are covered by self-insured
      health plans in which employers (or employee groups) bear all or some of the risk
      of providing insurance coverage to a defined population of workers and their
      dependents. As PPACA provisions become effective, some have argued that smaller
      firms that offer insurance may opt to self-insure their health benefits because
      of new small-group market rules. Such a shift could affect risk pooling in the
      small-group market. This paper examines the definition and prevalence of self
      insured health plans, the application of PPACA provisions to these plans, and the
      possible effects on the broader health insurance market, should many more
      employers decide to self-insure.

PMID- 21192489
TI  - [Proceedings of the Hepatitis C Consensus Conference, September 2004, Buenos
      Aires, Argentina].

PMID- 21192490
TI  - MEDINFO 2010. Proceedings of the 13th World Congress on Medical Informatics, Part
      1.

PMID- 21192491
TI  - On the need for porcine embryonic stem cells to produce Gal KO pigs expressing
      multiple transgenes to advance xenotransplantation research.

PMID- 21192492
TI  - Morphological changes of porcine islets of Langerhans after collagenase and HBSS
      infusion of the pancreas.
AB  - BACKGROUND: A remarkable change in porcine islet morphology was observed after
      infusion of the pancreas with collagenase. The aim of the present study was to
      quantify these morphological changes and to assess whether these changes were due
      to the volume expansion caused by the collagenase entering the islet or the
      result of its digestive effects. METHODS: This study was performed in pancreata
      of 28 crossbred pigs. First, eight pancreata were intraductally injected with
      collagenase by a continuous controlled pressure of 180 mmHg. Pancreas samples
      before collagenase infusion were used as controls. All tissue samples, both
      before and after infusion, were stained with anti-insulin. To quantify the
      morphological change of the islets, the mean beta cell/endocrine content ratio of
      the infused and not-infused tissue samples was compared. In a second experiment,
      20 pancreata were similarly assessed after intraductal injection with Hank's
      balanced salt solution (HBSS). RESULTS: In both the collagenase- and HBSS-infused
      groups, mean beta cell/endocrine content ratio was lower than in the control
      samples. The observed decline in the beta cell/endocrine content ratio was not
      significantly different between collagenase- and HBSS-infused pancreata. This
      suggests that the lower beta cell/endocrine content ratio and thus the
      morphological change in the infused tissue samples is caused by volume expansion
      of the fluid entering the islet and that the digestive effect of collagenase
      plays no or only a minor role. CONCLUSION: Morphological changes of islets are
      observed after infusion of pancreata with collagenase and HBSS, most likely
      caused by volume expansion due to fluid entering the islets.

PMID- 21192493
TI  - Multivisceral xenotransplantation--does it have a future?

PMID- 21192494
TI  - Endoscopic features in a model of multivisceral xenotransplantation.
AB  - INTRODUCTION: Xenotransplantation and multivisceral transplantation are advanced
      therapeutic methods that still require a scientific basis. There are no
      experimental models of multivisceral transplantation available, particularly not
      the monitoring by endoscopy. Here, we describe the endoscopic features in a model
      of multivisceral xenotransplantation. METHODS: The distal esophagus, stomach,
      intestine, colon, liver, pancreas, and the kidneys with a common vascular pedicle
      were harvested from rabbits and implanted in swine (group I, n = 9) or in rabbits
      (group II, n = 4). Endoscopy was performed in the stomach, jejunum, and ascending
      colon at four consecutive time points (immediate after surgery and 10, 90, and
      180 min after reperfusion). Lesions were macroscopically graded as mild,
      moderate, and severe. Biopsies were taken following sacrifice at 180 min after
      reperfusion. RESULTS: In group I, the stomach, jejunum, and colon manifested a
      progression of lesions with predominance of mild lesions after 10 min, mild to
      moderate lesions after 90 min, and moderate to severe lesions after 180 min. In
      animals from group II, endoscopy showed normal features at all time points after
      reperfusion. Histopathologic analysis confirmed the diagnosis of hyperacute
      rejection in group I. Grafts from group II animals presented normal or mild
      ischemic/reperfusion injury. CONCLUSION: All animals subjected to multivisceral
      xenotransplantation showed a progression of endoscopic lesions with time after
      transplantation, while animals subjected to allotransplantation showed no
      aberrations in endoscopy. We conclude that endoscopy is a useful tool in the
      assessment of hyperacute rejection of a xenograft.

PMID- 21192495
TI  - Combating evolving pathogens. Introduction.

PMID- 21192496
TI  - Medical negligence--Indian Penal Code and CPA vis-a-vis medical profession.

PMID- 21192497
TI  - Epilepsy genetics--an optimistic overview.

PMID- 21192498
TI  - Presence and severity of COPD among patients attending cardiology OPD of a
      tertiary healthcare centre.
AB  - Chronic obstructive pulmonary disease (COPD) and ischaemic heart disease (IHD)
      are two very common entities, which often coexist due to common risk factors
      notably smoking. Though both are common causes of chronically poor health, only
      cardiovascular disease has got major health priority and government research
      funding. COPD is largely underdiagnosed and even unsuspected among cases of IHD.
      The present study wants to address this relatively unexplored area of magnitude
      of COPD among cases of IHD. A total of 86 (male-65, female-21) consecutive stable
      and ambulatory IHD patients diagnosed by cardiologist and fulfilling the criteria
      for inclusion, were selected from cardiology outpatient department of IPGME&R,
      Kolkata from January 2005 to August 2006. Associated COPD was found in 51.2% (n =
      44) patients of the study group (males-36, females-8) according to GOLD criteria;
      90.9% of cases of COPD had moderate to severe disease. This was much higher than
      the prevalence of COPD among general population. A positive correlation was found
      between severity of COPD and impaired left ventricular ejection fraction (EF).
      This study also shows that general perception about COPD is poor among patients
      and their physicians. Most of the COPD cases (81.8%) of IHD were newly detected
      in this study by spirometric evaluation. Use of inhaled bronchodilator among the
      previously diagnosed cases is also very low (15.9%). Awareness regarding
      coexistence of the two diseases may be helpful in management and reduction of
      mortality and morbidity of COPD in IHD.

PMID- 21192499
TI  - Value of EEG in epilepsy.

PMID- 21192500
TI  - Refractory epilepsy.

PMID- 21192501
TI  - Epilepsy and women.

PMID- 21192502
TI  - Febrile seizure.

PMID- 21192503
TI  - Fine needle aspiration biopsy in the diagnosis of intraocular and extra-ocular
      mass lesions.
AB  - In a 3-year study with mass lesions related to ophthalmology 30 cases arising
      from ocular tissue, ocular adenaxae and orbit were subjected to fine needle
      aspiration biopsy. Of these 27 cases were further subjected to detailed
      histopathological examination. Fine needle aspiration biopsy revealed definitive
      cytological character in 23 cases consistent with histopathological and clinical
      diagnosis.

PMID- 21192504
TI  - Tissue adhesive in ophthalmology.
AB  - Tissue adhesive in ophthalmology is commonly used for corneal wound and
      restricted for superficial closure. Only synthetic adhesive available is butyl-2
      cyanoacrylate. However, if it gets between the wound margins it inhibits healing
      by forming impervious barrier.

PMID- 21192505
TI  - Mucosa associated lymphoid tissue lymphoma of lung: a case report.
AB  - Mucosa associated lymphoid tissue lymphoma is a rare disease particularly when
      occurring in the lungs. In 1983, Issacson and Wright first described it as a
      distinct clinicopathological entity. A 39-year-old woman was suffering from
      mucosa associated lymphoid tissue lymphoma of the lung and was treated with
      moderate dose radiotherapy only. Six months after treatment the woman is symptom
      free and without any evidence of relapse. The disease undergoes a very indolent
      course and local form of treatment like surgery or radiotherapy is effective
      though radiotherapy is probably associated with higher local control rate and
      event free survival particularly in early stages. But for diagnostic purpose
      thoracotomy is generally required in pulmonary variety. Due to rarity of cases it
      is almost impossible to compare surgery with radiotherapy in mucosa associated
      lymphoid tissue lymphoma disorder in a prospective manner. Radiotherapy is the
      preferred mode of treatment either alone or in combination with surgery.

PMID- 21192506
TI  - Postdural puncture headache.

PMID- 21192507
TI  - Federal actions. Passenger Vessels; Title II; title III; section 504.

PMID- 21192508
TI  - Illinois. Health care power of attorney.

PMID- 21192509
TI  - Venous thromboembolism in India.

PMID- 21192510
TI  - Toward more uniform conflict disclosures: the updated ICMJE conflict of interest
      reporting form.

PMID- 21192511
TI  - Association between domestic violence and unintended pregnancies in India:
      findings from the National Family Health Survey-2 data.
AB  - BACKGROUND: Violence against women, especially by their husbands, is a serious
      public health issue that is associated with physical, reproductive and mental
      health consequences. The association between physical violence and unintended
      pregnancies has not been explored in India. METHODS: Data were drawn from the
      second round of the National Family Health Survey (NFHS-2), India conducted in
      1998-99. Unintended pregnancy, defined as a pregnancy that was not wanted at the
      time of conception, was the dependent variable. A set of independent covariates
      such as age, place of residence, education, working status, religion, standard of
      living index, type of family, number of surviving sons, use of contraceptive
      methods, pregnancies terminated and physical mistreatment by the husband were
      evaluated using a step-wise multiple logistic regression model. RESULTS: Multiple
      logistic regression analysis showed that women who had been physically mistreated
      by their husbands were 47% (OR 1.47; 95% CI 1.25-1.72) more likely to experience
      unintended pregnancies. CONCLUSION: Preventing physical violence against women by
      their husbands could reduce unintended pregnancies.

PMID- 21192512
TI  - A prospective study of suicidal behaviour in Sundarban Delta, West Bengal, India.
AB  - BACKGROUND: Deliberate self-harm is a challenging public health issue but there
      is a paucity of data on non-fatal deliberate self-harm in the literature. We
      aimed to understand the behaviour of deliberate self-harm, both fatal and
      nonfatal, in a primary care setting. METHODS: A year-long prospective study of
      all admitted patients of deliberate self-harm at 13 block primary health centres
      of the Sundarban region was done to examine the sociodemographic profile and
      clinical outcome of suicidal behaviour. Data were collected by using an
      especially devised deliberate self-harm register. Each subject was administered a
      20-item case history sheet by trained medical officers and nursing staff.
      RESULTS: A total of 1614 deliberate self-harm subjects (619 men, 995 women) were
      admitted during the year, of whom 143 (62 men, 81 women) died. Although women,
      especially in the younger age groups, constituted the majority of subjects
      (61.6%), the fatality trend was higher among men than among women (10% v. 8.1%).
      Poisoning was the commonest (98.4%) method of self-harm, particularly using
      pesticide. Easy availability of pesticides was a risk factor. Psychosocial
      stressors, such as conflict with spouse, guardian or in-laws, failed love affairs
      and economic distress, were the common underlying reasons. The majority of acts
      of deliberate self-harm (92.6%) were committed inside the home, especially by
      women. Only a small proportion of subjects had a past or family history of
      attempt at deliberate self-harm. The overall incidence of fatal and non-fatal
      deliberate self-harm was 5.98 and 61.51 per 100 000 population, respectively.
      CONCLUSION: Both fatal and non-fatal pesticide-related deliberate self-harm is a
      major public health issue in the Sundarban region. An intersectoral approach
      involving primary health, administration and agriculture may help in developing
      an effective preventive programme to reduce the morbidity and mortality from
      deliberate self-harm.

PMID- 21192513
TI  - Risk factors for cardiovascular diseases: is the social gradient reversing in
      northern India?
AB  - BACKGROUND: In the past century, most developed countries witnessed a reversal of
      social gradient in cardiovascular diseases. To examine whether this phenomenon is
      also under way in developing countries, we assessed the prevalence of selected
      risk factors for cardiovascular diseases among different social groups living in
      urban and rural areas of northern India. METHODS: Four hundred adults > or =30
      years of age, selected by cluster sampling, were surveyed from 8 purposively
      selected communities of Chandigarh and Haryana during 2004-05. The WHO STEPS tool
      for surveillance of risk factors was used to enquire about sociodemographic
      characteristics, tobacco use, alcohol intake, physical activity and to measure
      weight, height, blood pressure, and waist and hip circumference. Prevalence of
      risk factors such as tobacco use, physical inactivity, overweight (BMI > or =25
      kg/m2), and hypertension (> or = 140/90 mmHg or on anti-hypertension treatment)
      were estimated according to the area of residence and across educational
      categories after controlling for the effects of confounding variables. RESULTS:
      The prevalence of hypertension in urban (39%; 95% CI 29.5%-49.2%), slum (35%; 95%
      CI 27.2%-42.9%) and rural (33%; 95% CI 25.4%-40.8%) communities was found to be
      statistically similar (p > 0.05) after controlling for age, gender and education.
      The prevalence of physical inactivity (17% v. 12%), central obesity (90% v. 88%),
      overweight (20% v. 19%) and hypertension (34% v. 36%), were found to be
      statistically similar among literate and illiterate population after controlling
      for the effect of age, sex and place of residence (p > 0.05). However, the risk
      of tobacco use was significantly lower among literates (OR 0.3, 95% CI 0.1-0.8).
      CONCLUSION: In selected communities of northern India, most of the cardiovascular
      disease risk factors did not have a social gradient except tobacco use, which was
      more common in the lower social group.

PMID- 21192514
TI  - Recent advances in the management of multiple myeloma.
AB  - Multiple myeloma is a disease of malignant plasma cells in the bone marrow.
      Interaction of malignant plasma cells with the bone marrow microenvironment plays
      a key role in the pathogenesis of the disease. The Introduction of two new
      classes of molecules, namely immunomodulators (e.g. thalidomide, lenalidomide),
      and proteasome inhibitors (e.g., bortezomib) has led to improvement in the
      management of myeloma. Induction therapy with these novel drugs in combination
      with dexamethasone is associated with higher response rates including complete
      response in one-fourth of patients with bortezomib combinations. Further
      consolidation with intensive chemotherapy supported by autologous stem cell
      transplant in young, eligible patients results in complete response in 50%-70% of
      patients with improved survival. Simplified criteria for staging, uniform
      response criteria, more sensitive methods for detection of residual disease
      (immunofixation and free light chain assay), and recognition of potential adverse
      cytogenetic and genomic abnormalities have further refined the management of
      patients with myeloma. Along with earlier diagnosis, improved treatment and
      better management of complications have resulted in longer disease control and
      survival with a better quality of life.

PMID- 21192515
TI  - Does BCG vaccination protect against childhood asthma?

PMID- 21192516
TI  - Chest radiographs in the ICU: routine or on demand?

PMID- 21192517
TI  - The challenge of cerebral palsy in India.

PMID- 21192518
TI  - Alcohol and public health policies in India.
AB  - Extreme policies of prohibition or the current permissive strategies are
      counterproductive and call for a nuanced public health approach that integrates
      both the regulation of availability of alcohol as well as helps in rigorously
      enforcing the law.

PMID- 21192519
TI  - Reflective writing by final year medical students: lessons for curricular change.
AB  - BACKGROUND: Reflective writinghas been used in undergraduate medical curricula to
      inculcate empathetic attitudes in medical students. Journal writing has been used
      to enhance reflection in a confidential space. We aimed to introduce our medical
      students to reflective writing of their daily experiences, both to enhance
      empathetic attitudes as well as to use the entries to Inform curricular changes.
      METHODS: We invited 16 final year medical students posted in the Department of
      Medicine to record their emotional experiences during a 6-week posting. Freedom
      to abstain without prejudice was emphasized, yet all 16 students complied.
      RESULTS: According to the principle of grounded theory, the entries were grouped
      into 8 themes: (i) doctor-patient relationship; (ii) personal inadequacy; (iii)
      empathy; (iv) communication skills; (v) doctor's competence; (vi) patient
      behaviour; (vii) hospital practices; and (viii) personal feelings. There were 179
      entries which were evaluable under the above categories, with no significant
      gender differences. Based on the entries, the following curricular suggestions
      were made: (i) use of diaries by medical students to express their emotional
      reactions and make value judgements, followed by guided discussion by experienced
      facilitators; (ii) introduction of communication skills courses at appropriate
      points to enhance Interview skills, empathetic listening, conflict resolution and
      breaking bad news; (iii) encourage reflection on healthcare delivery and its
      inequities and suggest methods of dealing with individual patients; and (iv) use
      of positive feedback and encouragement by faculty. Conclusions. Reflective
      journal writing by medical students in India gives valuable insights into
      improving communication skills and professionalism. Appropriate curricular
      changes should be made to meet the challenges posed by the existing healthcare
      system.

PMID- 21192520
TI  - Healthcare financing: approaches and trends in India.
AB  - Despite the importance of healthcare for the well-being of society, there is
      little public debate in India on issues relating to it. The 'human capital
      approach' to finance healthcare largely relies on private investment in health,
      while the 'human development approach' envisages the State as the guarantorof
      preventive as well as curative care to achieve universalization of healthcare.
      The prevailing health indices of India and challenges in the field of public
      health require a human developmentapproach to healthcare. On the eve of
      independence, India adopted the human development approach, with the report of
      the Bhore Committee emphasizing the role of the State in the development and
      provision of healthcare. However, more recently, successive governments have
      moved towards the human capital approach. Instead of increasing state spending on
      health and expanding the public health infrastructure, the government has been
      relying more and more on the private sector. The public-private partnership has
      been touted as the new-age panacea for the ills of the Indian healthcare system.
      This approach has led to a stagnation of public health indices and a decrease in
      the access of the poor to healthcare.

PMID- 21192521
TI  - Francois Bernier's discourse on the health system in medieval India.

PMID- 21192522
TI  - Disease prevention and an intervention.

PMID- 21192523
TI  - Drug rackets.

PMID- 21192525
TI  - Of the Medical Council of India and industry freebies.

PMID- 21192524
TI  - Photosensitive epilepsy in India.

PMID- 21192526
TI  - Bachelor of rural health care: cutting the root and watering the stem!

PMID- 21192527
TI  - An autoimmune disease in an immune deficiency disorder.

PMID- 21192528
TI  - Down but not out. The link between depression and diabetes.

PMID- 21192529
TI  - In his own words Bret Michaels and the years of living dangerously.

PMID- 21192530
TI  - Doing well and doing good. 12 people with diabetes who are helping others just
      like them.

PMID- 21192531
TI  - A new shine on an old med. The story of metformin's past, present, and possible
      future.

PMID- 21192532
TI  - Diabetes how to forecast. Craft a casserole.

PMID- 21192533
TI  - Economic conditions improve; directors strive to reduce costs.

PMID- 21192535
TI  - Manager 'excellent at building bridges'.

PMID- 21192534
TI  - A call for mandatory flu vaccinations.

PMID- 21192536
TI  - Laparoendoscopic single-site (LESS) surgery for adult urologic indications.

PMID- 21192537
TI  - What's your OR's greatest achievement?

PMID- 21192538
TI  - Allografts: overview of the process.

PMID- 21192539
TI  - Donor screening: first step in safety.

PMID- 21192540
TI  - Onboarding: OR observation, the interview, and job offer.

PMID- 21192541
TI  - Economy, Medicare squeeze ASCs.

PMID- 21192542
TI  - Developing a transfer plan for MH crisis.

PMID- 21192543
TI  - Parasites of the pleasure oyster Crassostrea corteziensis cultured in Nayarit,
      Mexico.
AB  - The pleasure oyster Crassostrea corteziensis is collected and cultured in Nayarit
      on the Pacific coast of Mexico, and the improvement and promotion of its culture
      are seen as a possible source for the economic development of coastal
      populations. However, information about the parasite fauna of the pleasure oyster
      is almost completely lacking. A histopathological survey carried out in two
      estuaries, Boca del Camichin and Pozo Chino, revealed the presence of
      hypertrophied gametes, rickettsiales-like prokaryotes (RLPs), the protozoan
      Perkinsus marinus, a protozoan Nematopsis sp., Ancistrocoma-like ciliates (ALCs),
      Sphenophrya-like ciliates, a turbellarian Urastoma sp., and encysted crustaceans.
      In general, prevalence and intensity of parasites were similar in both localities
      except that ALCs and encysted crustaceans were more prevalent in Pozo Chino than
      in Boca del Camichin. Perkinsus marinus and RLPs seem to represent a more
      significant risk for the health of pleasure oysters than do the other parasites,
      and surveillance and control of these parasites are needed for the development of
      pleasure oyster culture.

PMID- 21192544
TI  - Fecal hormones measured within giant Pacific octopuses Enteroctopus dofleini.
AB  - The captive husbandry of giant Pacific octopuses Enteroctopus dofleini is well
      understood, but their endocrine signatures are not well documented. The major
      vertebrate reproductive hormones--estrogen, progesterone, and testosterone--and
      the stress-related hormone corticosterone are relatively well known for many
      vertebrate species. However, few studies on these hormones within invertebrates
      have been conducted. Our hypothesis was that endocrine signatures within
      octopuses are similar to those found within vertebrates in response to
      reproductive activity and stress. Using standard immunoassay techniques, we
      measured fecal steroids within fecal samples collected from five female and three
      male giant Pacific octopuses housed at the Seattle Aquarium. The mean estrogen
      level ranged from 3.67 to 99.39 ng/g of feces, progesterone ranged from 44.35 to
      231.71 ng/g feces, testosterone ranged from 9.30 to 18.18 ng/g feces, and
      corticosterone ranged from 10.91 to 22.14 ng/g feces. The results suggest that
      octopus fecal hormones are similar to those in vertebrates and may be useful in
      measuring ovarian activity and stress within captive female giant Pacific
      octopuses.

PMID- 21192545
TI  - Determination of florfenicol dose rate in feed for control of mortality in Nile
      tilapia infected with Streptococcus iniae.
AB  - A dose titration study was conducted to determine the dosage of florfenicol (FFC)
      in feed to control Streptococcus iniae-associated mortality in Nile tilapia
      Oreochromis niloticus. Six tanks were assigned to each of five treatments: (1)
      not challenged with S. iniae and fed unmedicated feed; (2) challenged with S.
      iniae by injection and fed unmedicated feed; (3) challenged with S. iniae and
      given FFC at 5 mg/kg of body weight (bw) in medicated feed; (4) challenged with
      S. iniae and given 10 mg FFC/kg bw; and (5) challenged with S. iniae and given 15
      mg FFC/kg bw. Treatment was initiated the day after inoculation, and feed was
      administered for 10 d. Cumulative mortality was 0% in the unchallenged, untreated
      group; 35.8 +/- 4.4% (mean +/- SE) in the challenged, unmedicated group; 19.2 +/-
      2.7% in the 5-mg/kg treated group, 12.5 +/- 3.8% in the 10-mg/kg group, and 2.5
      +/- 1.1% in the 15-mg/kg group. The cumulative mortality was significantly less
      in each challenged, FFC-treated group than in the challenged, unmedicated
      controls (5 mg/ kg: P = 0.0156; 10 mg/kg: P = 0.0007; 15 mg/kg: P < 0.0001). The
      efficacy of the 10- and 15-mg/kg FFC dosages was studied in a separate dose
      confirmation study. Fish in all tanks were injected with S. iniae. At 4 h
      postinoculation, 10 tanks were assigned to each of three feed treatments: (1)
      unmedicated feed; (2) 10 mg FFC/kg bw; and (3) 15 mg FFC/kg bw. Cumulative
      mortality was 20.5 +/- 2.0% in the challenged, unmedicated group; 11.0 +/- 2.1%
      in the 10-mg/kg group; and 5.5 +/- 2.4% in the 15-mg/kg group. Mortality was
      significantly less in the medicated groups than in the challenged, unmedicated
      control group (10 mg/kg: P = 0.0270; 15 mg/kg: P = 0.0007). Fish in both studies
      were necropsied, cultured for bacteria, and examined for gross lesions. The
      minimum inhibitory concentration of FFC against S. iniae in both studies ranged
      from 0.5 to 1.0 microg/mL. Florfenicol was palatable, safe, and efficacious for
      control of Nile tilapia mortality due to S. iniae infection.

PMID- 21192546
TI  - Serum electrolyte and nonelectrolyte status in freshwater juvenile Persian
      sturgeon Acipenser persicus.
AB  - Status of serum electrolyte and nonelectrolyte variables can be used for managing
      sturgeon species cultured in freshwater or living in seawater. The aim of the
      present study was to evaluate serum biochemical variables in clinically healthy
      juvenile Persian sturgeon Acipenser persicus cultured in freshwater. Serum
      samples from 11 females and 10 males were analyzed, and levels (mean +/- SD) of
      the following variables were compared between sexes: glucose (Glc; 5.58 +/- 1.25
      mmol/L for females and 8.56 +/- 1.80 mmol/L for males), total cholesterol (TC;
      2.50 +/- 0.45 and 2.40 +/- 0.65 mmol/L), triglyceride (TG; 7.13 +/- 2.68 and 5.14
      +/- 1.27 mmol/L), blood urea nitrogen (BUN; 1.28 +/- 0.2 and 1.01 +/- 0.2
      mmol/L), total protein (TOP; 55.84 +/- 8.77 and 41.44 +/- 8.62 g/L), inorganic
      phosphate (P(i); 6.19 +/- 1.02 and 5.23 +/- 0.49 mmol/L), calcium (Ca; 2.80 +/-
      0.43 and 2.63 +/- 0.32 mmol/L), magnesium (Mg; 0.9 +/- 0.23 and 0.99 +/- 0.22
      mmol/L), sodium (Na; 152.80 +/- 13.81 and 156.38 +/- 12.67 mmol/L), potassium (K;
      2.64 +/- 0.58 and 2.27 +/- 0.39 mmol/L), and chloride (Cl; 143 +/- 13.85 and
      151.67 +/- 21.08 mmol/L). There were no differences in TC, Ca, Mg, Na, K, or Cl
      between sexes. The Glc value was lower in female Persian sturgeon than in males,
      whereas the values of TG, BUN, TOP, and P(i) were higher in females than in
      males. Freshwater adaptation may affect serum ion concentrations in juvenile
      Persian sturgeon.

PMID- 21192547
TI  - Observations and treatment of Nitzschia sturionis on Atlantic sturgeon from
      Chesapeake Bay.
AB  - From 2004 to 2008, 10% of Atlantic sturgeon Acipenser oxyrinchus oxyrinchus
      examined during a bycatch study of Maryland's Chesapeake Bay were infested with
      the trematode Nitzschia sturionis on the skin and gills. The parasite intensity
      increased on 75% of infested fish 4-24 months after being placed in captivity.
      Mean parasite intensity increased to a greater extent on the skin (up to 100
      fold) than on the gills (up to 16-fold). Atlantic sturgeon that were infested
      with N. sturionis gained weight at a reduced rate or lost weight compared with
      uninfested fish. Skin lesions associated with N. sturionis progressed from a few
      reddened foci to hemorrhagic ulcers and depigmentation, while gill lesions showed
      a less-dramatic progression. Host tissues identified in the intestinal ceca of N.
      sturionis consisted primarily of malpighian cells, but small amounts of blood
      were also found in worms attached to lesions in the skin and gills. An Atlantic
      sturgeon infested with approximately 500 worms was successfully treated with a 3
      h bath of praziquantel at 10 mg/L. This first report of N. sturionis from
      Chesapeake Bay extends the parasite's reported southern range in North America.

PMID- 21192548
TI  - Spatial and temporal distribution of the Asian fish tapeworm Bothriocephalus
      acheilognathi (Cestoda: Bothriocephalidea) in the Rio Grande (Rio Bravo del
      Norte).
AB  - Recent collections of the Asian fish tapeworm Bothriocephalus acheilognathi in
      the Rio Grande have raised concern about the potential impacts on Rio Grande
      endemic and imperiled fishes. The objectives of this study were to determine
      distribution and definitive hosts of the Asian fish tapeworm within the Rio
      Grande drainage and to quantify occurrences and abundances. In total, 1,992 fish
      spanning 11 families were collected and examined for Asian fish tapeworms in the
      Rio Grande and the Pecos and Devils rivers. The parasite was collected from red
      shiners Cyprinella lutrensis, Tamaulipas shiners Notropis braytoni, sand shiners
      N. stramineus, river carpsuckers Carpiodes carpio, plains killifish Fundulus
      zebrinus, western mosquitofish Gambusia affinis, blue suckers Cycleptus
      elongatus, blacktail shiners Cyprinella venusta, proserpine shiners Cyprinella
      proserpina, and Manantial roundnose minnow Dionda argentosa, with the latter four
      species being new host records. Monthly collections of red shiners from Big Bend
      National Park exhibited prevalence levels above 15% in January-March and December
      and below 10% during April-June and October. With over 50% of the Rio Grande
      icthyofauna in Texas considered imperiled, the occurrence and pathological
      effects of the Asian fish tapeworm in combination with reduced water quantity and
      quality and increased habitat fragmentation are of concern for these taxa.

PMID- 21192549
TI  - Mortality of centrarchid fishes in the Potomac drainage: survey results and
      overview of potential contributing factors.
AB  - Skin lesions and spring mortality events of smallmouth bass Micropterus dolomieu
      and selected other species were first noted in the South Branch of the Potomac
      River in 2002. Since that year morbidity and mortality have also been observed in
      the Shenandoah and Monocacy rivers. Despite much research, no single pathogen,
      parasite, or chemical cause for the lesions and mortality has been identified.
      Numerous parasites, most commonly trematode metacercariae and myxozoans; the
      bacterial pathogens Aeromonas hydrophila, Aeromonas salmonicida, and
      Flavobacterium columnare; and largemouth bass virus have all been observed. None
      have been consistently isolated or observed at all sites, however, nor has any
      consistent microscopic pathology of the lesions been observed. A variety of
      histological changes associated with exposure to environmental contaminants or
      stressors, including intersex (testicular oocytes), high numbers of macrophage
      aggregates, oxidative damage, gill lesions, and epidermal papillomas, were
      observed. The findings indicate that selected sensitive species may be stressed
      by multiple factors and constantly close to the threshold between a sustainable
      (healthy) and nonsustainable (unhealthy) condition. Fish health is often used as
      an indicator of aquatic ecosystem health, and these findings raise concerns about
      environmental degradation within the Potomac River drainage. Unfortunately, while
      much information has been gained from the studies conducted to date, due to the
      multiple state jurisdictions involved, competing interests, and other issues,
      there has been no coordinated approach to identifying and mitigating the
      stressors. This synthesis emphasizes the need for multiyear, interdisciplinary,
      integrative research to identify the underlying stressors and possible management
      actions to enhance ecosystem health.

PMID- 21192550
TI  - Suit: CVS violating HIPAA privacy.

PMID- 21192551
TI  - Fed advisors: use CORE, NCDPD operating rules.

PMID- 21192552
TI  - Feds ready national claims database.

PMID- 21192553
TI  - Regional extension centers start to roll.

PMID- 21192554
TI  - Solving the cash flow conundrum.

PMID- 21192555
TI  - Loop holes.

PMID- 21192556
TI  - I.T. eases the pain of flu season.

PMID- 21192557
TI  - Testing, testing. Interview by Elizabeth Gardner.

PMID- 21192558
TI  - The tipping point: it's time for oncologists to prepare for change.

PMID- 21192559
TI  - Radiation therapy in the management of diffuse large B-cell lymphoma: still
      relevant?
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin
      lymphoma in the United States. Historically, radiation therapy (RT) was the
      primary treatment for patients with localized disease. Several randomized trials
      have demonstrated that the addition of systemic therapy improves outcomes.
      Additional randomized trials have shown that the combination of RT and systemic
      therapy is superior to systemic therapy alone. The role of RT in advanced-stage
      DLBCL has not been firmly established, but some prospective phase III trials, as
      well as retrospective studies, suggest a benefit for advanced disease also. For
      patients with relapsed or primary refractory disease, autologous stem cell
      transplantation is the treatment of choice. Here too, consolidation RT appears to
      improve outcomes compared with autologous stem cell transplant alone. Finally,
      for patients with advanced DLBCL who are no longer responsive to systemic
      therapy, RT may provide rapid and durable palliation of local lymphoma-related
      symptoms.

PMID- 21192560
TI  - Radiation for diffuse large B-cell lymphoma: more questions than answers.

PMID- 21192561
TI  - Unanswered questions: monoclonal antibodies in the treatment of advanced non
      small-cell lung cancer.
AB  - First-line platinum-based doublets is established as the standard of care for
      advanced non-small-cell lung cancer (NSCLC). Nevertheless, in this field a
      plateau of effectiveness has been reached during the last years. One new area of
      exploration in NSCLC therapeutics lies in the use of tyrosine-kinase inhibitors
      (TKIs) or monoclonal antibodies (mAbs) to target vascular endothelial growth
      factor (VEGF) and its receptors, and epidermal growth factor receptor (EGFR). The
      results of randomized trials testing mAbs against VEGF (bevacizumab) and EGFR
      (cetuximab) are challenging the paradigm of the platinum doublets as the gold
      standard in advanced NSCLC. Despite the interesting results that have thus far
      been collected, the benefit of these new agents, both in terms of balancing
      between advantages and toxicity and the associated health economic burden, is
      modest. Here we discuss the use of bevacizumab and cetuximab, the mAbs for which
      the largest amount of data in the treatment of advanced NSCLC exists. However,
      despite our having a significant amount of data on these two mAbs, we still have
      much to learn: Which patients are appropriate for these treatments; for how long
      are the treatments beneficial, and what are the molecular and clinicalpredictors?
      We must continue to study these important problems in treating NSCLC.

PMID- 21192562
TI  - Bevacizumab in advanced lung cancer: in search of the right drug for the right
      patient.

PMID- 21192563
TI  - Future directions of monoclonal antibody use in personalized lung cancer therapy.

PMID- 21192564
TI  - The Breast Health Global Initiative: why it matters to all of us.
AB  - The Breast Health Global Initiative (BHGI) applied an evidence-based consensus
      review process to the development of guidelines for breast cancer early
      detection, diagnosis, treatment and health care systems in low- and middle-income
      countries (LMCs). Breast cancer outcomes correlate with the degree to which (1)
      cancers are detected at early stages, (2) newly detected cancers can be diagnosed
      correctly, and (3) appropriately selected multimodality treatment can be provided
      properly and in a timely fashion. Cancer prevention through health behavior
      modification may influence breast cancer incidence in LMCs, although prevention
      strategies alone cannot eliminate the great majority of breast cancer cases.
      Diagnosing breast cancer at earlier stages will reduce breast cancer mortality,
      assuming that appropriate multimodality treatment is provided. Programs to
      promote breast self-awareness and clinical breast examination and resource
      adapted mammographic screening are important steps in early detection. Obstacles
      to breast cancer early detection, diagnosis, and treatment occur in
      industrialized countries as well as LMCs. Understanding implementation in LMCs
      can inform policy makers in the U.S. on how to improve health care delivery in
      underserved communities, where the challenges mirror those of low-resource
      environments.

PMID- 21192565
TI  - Research training in breast cancer for low and middle income countries.

PMID- 21192566
TI  - International disparity in breast cancer outcomes: the time to close the gap is
      now.

PMID- 21192567
TI  - Why my neighbor's health is important to me.

PMID- 21192568
TI  - Oleander (Nerium oleander).

PMID- 21192569
TI  - Pierre prepares a patient for the operating theatre.

PMID- 21192570
TI  - Tribute to Representative Ben Chandler: Standing tall for aged, infirm, and
      disabled Americans.

PMID- 21192571
TI  - An interview with James Mapes: taking a quantum leap to live an exceptional life.
      Interview by Val J Halamandaris.

PMID- 21192572
TI  - VNA of Texas help make the holidays merrier for its home care patients.

PMID- 21192573
TI  - Indiana home care and hospice agency's 'Orange Friday' community charity program
      earns recognition.

PMID- 21192574
TI  - Home care and hospice: much more than just health care.

PMID- 21192575
TI  - Alzheimer's Disease Awareness Month: how home care can help.
AB  - In November, among other themes, we recognize National Alzheimer's Awareness
      Month. Despite the sobering fact that there is still no cure for Alzheimer's
      disease, this year we have witnessed some very exciting progress toward that
      goal, and home care continues to play a crucial role in meeting the needs of
      those with Alzheimer's disease and their loved ones.

PMID- 21192576
TI  - OASIS, scope of practice, and the therapies.

PMID- 21192577
TI  - Hospices: now's the time to prepare for medical review.

PMID- 21192578
TI  - Give your customers an occasional miracle.

PMID- 21192579
TI  - Cause marketing meets social media: boosting your agency's profile while making a
      difference.

PMID- 21192580
TI  - Live from Iquitos.

PMID- 21192581
TI  - Striving for transformational change: visionary leadership.

PMID- 21192582
TI  - See no evil, hear no evil, speak no evil.

PMID- 21192583
TI  - Endoskeletal ossicular reconstruction using the Kraus K-Helix Crown and Piston
      middle ear prostheses.
AB  - The Kraus K-Helix Crown and Piston prostheses are novel, newly designed, MRI
      compatible, titanium ossicular replacement prostheses that have received U.S.
      Food and Drug Administration clearance in March of 2008 for ossiculoplasty.
      Reconstruction is indicated to restore sound conduction of the ossicular chain
      during tympanoplasty in chronic and non-chronic ears. The prostheses have been
      specifically developed for reconstruction of an eroded or absent long process of
      the incus and an eroded or absent stapes superstructure. They may be used with or
      without glass-ionomer cement. The prostheses may be implanted incus-to-stapes or
      malleus-to-stapes (K-Helix Crown) or may be implanted incus-to-footplatelneo
      membrane or malleus-to-footplate/neo-membrane (K-Helix Piston). The K-Helix
      Piston is useful during revision stapedectomy when an eroded long process of the
      incus is encountered. By coating the K-Helix prostheses with glass-ionomer
      cement, it is possible to perform "endoskeletal ossicular reconstruction" which
      greatly enhances long-term prosthesis stability and avoids contact with the
      tympanic membrane. The prostheses may be custom-fit to reconstruct each
      individual patient's anatomy. Preliminary hearing results in a small cohort of
      patients at one year indicate very satisfactory hearing results with closure of
      the air-bone gap in the majority of patients. The ENT OR nurse plays a role in
      the use of specialized, adjunctive OR equipment that is used with the technology,
      is required for the preparation of glass-ionomer cement, and provides patients
      with important educational information concerning reconstructive otologic
      procedures.

PMID- 21192584
TI  - What does the Healthcare Reform Act have to do with me? Plenty! Read on.

PMID- 21192585
TI  - Dollar and cents of healthcare.

PMID- 21192586
TI  - Snapshot of a nurse.

PMID- 21192587
TI  - Autumn--the season of changing leaves and political elections.

PMID- 21192589
TI  - Immigration.

PMID- 21192588
TI  - Doing the math: calculating nursing value.

PMID- 21192590
TI  - Standards set for advanced nurses.

PMID- 21192591
TI  - I'm lovin' it: would McDonald's food encourage hospital patients to eat?

PMID- 21192592
TI  - Falls in people with learning disabilities: what are the risk factors and
      prevention strategies?
AB  - There is a high prevalence of falls and related injuries in adults with learning
      disabilities. This article highlights the latest evidence on the diverse risk
      factors for falls among this group. Research into effective falls management
      strategies is sparse, but there is some evidence to indicate that environmental
      management, strength and balance training, and careful management of medications
      may help to reduce falls. Nurses can play an important role by identifying those
      who are at most risk, implementing management strategies and educating others.

PMID- 21192593
TI  - Postoperative pain 2: patient education, assessment and management.
AB  - Postoperative pain is poorly managed, with up to 67% of patients in the U.K.
      experiencing unnecessary moderate to severe pain. Part 1 of this two part series
      explored physiological mechanisms involved in the perception of pain and the role
      of psychological and environmental influences on how patients respond to it. This
      second part explores the principles of patient assessment and management of
      postoperative pain, and discusses acute pain analgesic guides.

PMID- 21192594
TI  - Can nurse prescribing improve medication concordance in people with dementia?
AB  - Research has suggested nurse prescribing can improve medication concordance in
      older people with mental health problems. An independent nurse prescriber at a
      memory clinic in Berkshire used a questionnaire to determine dementia patients'
      attitudes to and awareness of nurse prescribing. This article describes how the
      survey responses were used to improve medication adherence.

PMID- 21192595
TI  - Are first year undergraduate student nurses prepared for self directed learning?
AB  - BACKGROUND: Changing demands on the nursing workforce have led to considerable
      changes in undergraduate nurse education. Nurse educators have sought to
      incorporate self directed learning (SDL) into the curriculum to encourage student
      nurses to be proactive in their learning needs. AIM: To identify first year
      students' experiences and perspectives of SDL, and to determine whether they are
      prepared for it. METHOD: The study involved one cohort of pre-registration first
      year student nurses at the University of Wolverhampton. A questionnaire was used
      to identify their expectations, understand the reasons for different rates of
      learner progress, and identify ways that students learn best. A literature review
      was also carried out to explore SDL research and understand the concept in nurse
      education. RESULTS: The majority of the study participants had heard of SDL but
      lacked understanding of its concept, purpose and nature. Students were also
      unclear about what their role as a self-directed learner would involve, and a
      lack of clear direction for SDL in the curriculum was identified. CONCLUSION: SDL
      can be used to assist student learning in conjunction with methods that are
      teacher led. The progression to SDL requires a shift in emphasis from teaching to
      facilitation, and the views of nurse educators about their role in SDL need to be
      explored in depth. A clear strategy for introducing SDL into the nursing
      curriculum is required. It should also be adopted in a systematic manner in order
      to address the variations in students' educational attainment upon entry to their
      undergraduate courses.

PMID- 21192596
TI  - Our Victorian approach to HCAs puts patients at risk.

PMID- 21192597
TI  - You can't lump tattoos together with cataracts.

PMID- 21192598
TI  - Back our fight to get nurses onto boards.

PMID- 21192599
TI  - 500 m pounds promised for health visitors in white paper plans.

PMID- 21192600
TI  - Why are nurses failing to carry out digital rectal examinations?

PMID- 21192601
TI  - What leadership skills will community nurses need to improve outcomes in the new
      NHS?
AB  - Nurse leadership in the community will be more important than ever if the health
      service is to improve the health of the population. This article looks at the
      essential leadership skills nursingprofessionals working in primary care will
      need if they are to fulfil government healthcare plans to improve health and
      wellbeing.

PMID- 21192603
TI  - Treating plantar warts: what to do when patients take matters into their own
      hands.

PMID- 21192602
TI  - Developing champions to enhance the care of people with dementia in general
      hospitals.
AB  - In NHS Ayrshire and Arran, almost 5500 people have a dementia diagnosis. This
      could increase by as much as 60% over the next 20 years (Alzheimer Scotland,
      2007). National dementia strategies in the U.K. have identified a need for better
      training that supports staff in general hospitals. While all clinical settings
      will admit people with dementia, their specialist care needs are not always being
      met Better awareness will help ensure these are addressed on both admission and
      throughout their care journey. This is the second article describing a nurse led
      initiative to improve approaches towards dementia in a general community
      hospital. The first article (Crabtree and Mack, 2010) focused on raising
      awareness of dementia, while this follow-up article describes the development and
      implementation of a dementia champions programme.

PMID- 21192604
TI  - Exploring the clinical effects of height elevation and depression on syringe
      pumps.
AB  - Research has shown that the positioning of syringe pumps can have a significant
      effect on the amount of drug delivered t opatients. This article explains the
      effects of raising and lowering syringe pumps in relation to the entry site, and
      its impact on drug delivery. It also discusses drugs which are particularly
      associated with risks to patients when the device height is changed, and measures
      to reduce the clinical impact of height elevation and depression of infusion
      lines, including training.

PMID- 21192605
TI  - Interviewing student and qualified nurses to find out what makes an effective
      mentor.
AB  - BACKGROUND: A research project was undertaken to explore what constitutes a
      successful mentor. AIM: To increase understanding within the profession as to
      what makes an effective mentor. METHOD: The study mainly used qualitative
      methods, initially involving interviews with eight third year mental health
      student nurses, and postal questionnaires sent to 270 qualified mentors. RESULTS:
      A positive attitude and being highly motivated are important attributes for both
      the mentor and student, if mentoring is to be effective. Mentors felt that having
      formal supervision would ensure theywere supported appropriately. They also
      suggested they needed protected time to mentor to develop effective working
      relationships. CONCLUSION: Effective mentoring produces effective students, who
      in turn become competent, confident registrants.

PMID- 21192606
TI  - Add value to care by getting involved in commissioning.

PMID- 21192607
TI  - Are the British a nation of Victor Meldrews?

PMID- 21192609
TI  - Expensive 'doorstops'.

PMID- 21192608
TI  - Prepare your office for the big one.

PMID- 21192610
TI  - Information morality.

PMID- 21192611
TI  - Effects of different surface preparations on shear bond strength of orthodontic
      brackets to porcelain.
AB  - The aim of this study was to assess bonding of orthodontic metal brackets to
      porcelain surfaces using various surface treatment methods. Etching the porcelain
      with 9.6 percent HF followed by a bonding agent or silane application provided
      high and acceptable shear bond strengths.

PMID- 21192612
TI  - Dentistry from the perspective of the San Francisco phone book.
AB  - A population study of all San Francisco dental practices identified
      characteristics of Yellow Pages listings and display ads and practice
      characteristics such as dentists' ages, fictitious business names, and history of
      disciplinary actions. Older practitioners, those with multiple offices, and
      dentists who experienced disciplinary actions were more likely to be listed in
      the Yellow Pages and to use display ads. Just more than half of fictitious
      business names were registered with the California Dental Board.

PMID- 21192613
TI  - Maxillofacial penetrating injury by a grinding disc: a case report.
AB  - The authors report a rare case of a patient who sustained a penetrating angle
      grinder broken disc injury to his face, which resulted from a work accident.
      Evaluation and management are described.

PMID- 21192614
TI  - Oral malignancy--an uncommon presentation with sinus tract opening: a case
      report.
AB  - Routine cases of oral carcinomas may present with history of longstanding
      nonhealing lesion of the ulcero-proliferative type with a rolled or indurated
      border. They are most often diagnosed accurately based on clinical evidence,
      radiographs, and histopathology. However, patients can present with confusing
      clinical features that can pose diagnostic dilemma with other lesions of the
      orofacial region. This paper presents a case of malignancy with swelling with
      concurrent sinus openings.

PMID- 21192615
TI  - Sharp end to a hairy situation.

PMID- 21192616
TI  - Breakthrough in awareness of head, neck and mouth cancers.

PMID- 21192617
TI  - The specialist. Interview by Paul O'Grady.

PMID- 21192618
TI  - An audit of the quality of referral letters received by the Department of Oral
      and Maxillofacial Surgery, Dublin Dental School and Hospital.
AB  - One hundred consecutive referral letters, sent by dental practitioners to the
      Department of Oral and Maxillofacial Surgery, Dublin Dental School and Hospital,
      were audited in terms of quality. The audit was based on the Scottish
      Intercollegiate Guidelines Network (SIGN) recommendations of 1998. The audit
      demonstrated that in general referral letters required modification and did not
      give the clinician the required information. This paper sets out the results of
      the audit and suggests a template that should be used for future referrals.

PMID- 21192619
TI  - Factors influencing the provision of removable partial dentures by dentists in
      Ireland.
AB  - Factors influencing clinical treatment of partially dentate patients are varied,
      and there is a need to identify factors influencing success in the provision of
      removable partial dentures. The aim of this study was to assess the attitudes of
      general dental practitioners (GDPs) in Ireland towards tooth replacement and use
      of RPDs, in partially dentate older adults. The sample frame was the Register of
      Dentists in Ireland; data were also collected from a sample of dentists
      practising under NHS regulations in Northern Ireland. Validated questionnaires
      were sent to all dentists on the Register of Dentists in the Republic of Ireland,
      and dentists working under NHS regulations registered with the Central Services
      Agency in Northern Ireland. Content of the questionnaire included details of the
      dentist themselves, their dental practice and the profile of partial denture
      provision. They were also asked to give their views on factors influencing the
      success or failure of an RPD, the process of providing RPDs and their attitudes
      to RPD provision. A total of 1,143 responses were received, a response rate of
      45%. A mean number of 61 RPDs per annum were provided, with 75% of dentures
      provided being acrylic based. Respondents indicate their belief that cobalt
      chromium based dentures had a longer prognosis than acrylic dentures, but less
      than half (46%) claim to design the frameworks themselves. Patients' attitudes
      are considered influential in the success of RPD provision, and their influence
      on appearance is considered the most important factor influencing success. The
      most important factors influencing failure are: the patient not requesting a
      denture; an RPD restoring unbounded saddles; and, lower RPDs. Although considered
      important, approximately 60% of the sample do not routinely organise follow-up
      appointments for patients provided with RPDs. The fee structures in the DTSS and
      DTBS are considered a barrier to quality in the provision of partial dentures.

PMID- 21192620
TI  - Quiz. Desquamative gingivitis.

PMID- 21192621
TI  - Partnership agreements.

PMID- 21192622
TI  - Non-verbal communication.

PMID- 21192623
TI  - Amalgam waste disposal.

PMID- 21192624
TI  - The risk of bronchospasm in asthmatics undergoing general anaesthesia and/or
      intravascular administration of radiographic contrast media. physiopatology and
      clinical/functional evaluation.
AB  - It is well known that patients suffering from bronchial asthma undergoing to
      surgical procedures requiring general anaesthesia (GA) or the administration of
      water soluble radiographic contrast media (RCM) experience a risk of potentially
      severe bronchospasm. Nevertheless, little attention has been devoted on the
      possible preventive measures to reduce the occurrence of this potentially life
      threatening event. It has been shown that the most important risk factor for
      bronchospasm during GA induction and/or the use of RCM is represented by a high
      degree of bronchial hyperreactivity with airway instability not adequately
      controlled by long-term anti-inflammatory treatment. The aim of this review is to
      underline the need for an accurate clinical and functional evaluation of
      asthmatics (especially those with a relevant degree of asthma severity)
      undergoing GA or administration of RCM. Guidelines shared by pulmonologists,
      allergologists, anesthesiologists and radiologists should be produced in the
      future for a better evaluation and management of these patients. General
      practitioner plays an important role in managing asthmatic patients in "Real
      Life". It is likely that "Real Life"--optimally controlled asthmatics could
      undergo GA/RCM with lower risks especially in emergency conditions when it is not
      possible to perform any preoperative evaluation.

PMID- 21192625
TI  - Cetirizine premedication prevents acute urticaria induced by weak COX-1
      inhibitors in multiple NSAID reactors.
AB  - BACKGROUND: In multiple NSAID reactors, intolerance to weak COX-1 inhibitors may
      pose relevant therapeutic problems when painful, febrile or rheumatic disorders
      co-exist. OBJECTIVE: To assess whether pre-medication with a second generation
      antihistamine is able to prevent urticaria induced by "alternative" NSAIDs.
      METHODS: 87 with a history of urticaria following the administration of multiple,
      chemically unrelated NSAID underwent 250 oral tolerance tests with alternative
      drugs exerting little or no COX-1 inhibition (paracetamol, coxibs, nimesulide,
      tramadol). Twenty-eight challenges scored positive in 21 subjects: 8, 5, 9, and 6
      reactions were induced by paracetamol, tramadol, coxibs, and nimesulide,
      respectively. Thirteen of 21 underwent a new oral challenge with the offending
      drug(s) 2-6 hours after taking cetitrizine 10 mg. RESULTS: All the drugs were
      tolerated on re-challenge except paracetamol that was not tolerated in 2/4 cases.
      CONCLUSION: In most cases urticaria induced by alternative drugs exerting little
      or no COX 1-inhibition is slight, and can be adequately prevented by oral
      antihistamine pre-medication. These observations open new opportunities for
      patients with multiple NSAIDs intolerance that have to treat painful or febrile
      conditions or rheumatic disorders.

PMID- 21192626
TI  - Assessment of airborne soy-hull allergen (Gly m 1) in the Port of Ancona, Italy.
AB  - BACKGROUND: Epidemic asthma outbreaks are potentially a very high-risk medical
      situation in seaport towns where large volumes of soybean are loaded and unloaded
      Airborne allergen assessment plays a pivotal role in evaluating the resulting
      environmental pollution. OBJECTIVE: The aim of this study was to measure the
      airborne Gly m 1 allergen level in the seaport of Ancona in order assess the
      soybean-specific allergenic risk for the city. METHODS: Allergen and PM10 were
      evaluated at progressive distances from the port area. Allergen analysis was
      performed by monoclonal antibody-based immunoassay on the sampled filters. Daily
      meteorological data were obtained from the local meteorological station. For
      estimating the assimilative capacity of the atmosphere, an approach based on
      dispersive ventilation coefficient was tried. RESULTS: The allergen
      concentrations detected were low (range = 0.4-171 ng/m3). A decreasing gradient
      of the airborne allergen from the unloading area (22.1 +/- 41.2 ng/m3) to the
      control area (0.6 +/- 0.7 ng/m3) was detected. The concentration of the airborne
      Gly m 1 was not coupled with the presence of the soy-carrying ships in the port.
      A statistically significant relationship between airborne allergen, PM10 and
      local meteorological parameters quantifies the association with the atmospheric
      condition. CONCLUSION: Airborne Gly m 1 is part of the atmospheric dust of
      Ancona. The low level of this allergen seems consistent with the absence of
      asthma epidemic outbreak.

PMID- 21192627
TI  - Asthma: specific clinical and functional characteristics in childhood. Results of
      a national program in Romanian asthmatic children.
AB  - Childhood asthma presents with specific clinical and functional characteristics.
      The aim of our study was the description of a large cohort of asthmatic children.
      It was also to assess their outcome with maintenance therapy according to
      guidelines, and to analyze the relationship with baseline's characteristics. We
      focused particularly on clinical and functional pediatric specificities. METHODS:
      Prospective study driven on asthmatic children, without treatment, recruited
      during a hospitalization for exacerbation or a visit for uncontrolled asthma,
      treated according to GINA guidelines and followed for one year. RESULTS: 412
      children (mean age: 11.6 years +/- 2.7), were included. The level of severity
      was: intermittent asthma for 30% and persistent asthma for 70% (40.5% mild, 28%
      moderate, 1.5% severe). Mean prebeta2-FEV1 was 88.5% +/- 10.5 (PV) with mean
      beta2-reversibility of 10.8% +/- 7.8 (> 12% for 42% patients). 374 patients ended
      the study. After one year, we observed an improvement of clinical symptoms (p <
      0.0001), rate of hospitalization (p < 0.0001), and lung function (mean prebeta2
      FEV1: 91.2% +/- 7.9, p < 0.001). Asthma control was obtained for only 24.6%.
      Multivariate analysis show that decrease of symptoms was significantly related to
      younger age, higher level of initial severity and number of days of
      hospitalization. CONCLUSION: This study confirms pediatric specificities of
      asthma, as a normal FEV1 level and a limited beta2-reversibility of FEV1, and the
      large part of uncontrolled asthma after one year of treatment. It emphasizes the
      risk of undertreatment in a strategy based on severity. It argues for the regular
      assessment of control as now recommended, taking into account the pediatric
      asthma specificities.

PMID- 21192629
TI  - Treat fatty liver disease to reduce heart risk.  Some experts suggest that fatty
      liver disease will be the next big metabolic disorder associated with obesity and
      inactivity.

PMID- 21192628
TI  - Hyper-IgM syndrome--a case report and a clinical perspective.
AB  - The authors describe the case of a 28-year-old woman, with a history of recurrent
      bacterial infections since childhood and multiple hospitalizations for pneumonia,
      with important pulmonary sequelae, including bronchiectasis which warranted the
      need to perform a left lobectomy and lingulectomia at age 13. After diagnostic
      work up, the diagnosis of hypogammaglobulinemia with hyper-IgM was established,
      and she began regular replacement i.v. immunoglobulin treatment, with good
      tolerance and no side effects. A sequencing of the entire coding region (exons 1
      5) of the AICDA gene was performed, and a homozygous c.260G > C mutation was
      identified, confirming the diagnosis of type 2 hyper-IgM syndrome. This case
      illustrates the negative impact that a delay in diagnosis and hence delay in
      treatment has in patients with primary immunodeficiency since early therapy is
      the only way to reduce the incidence and severity of complications.

PMID- 21192630
TI  - Clinical roundtable monograph. New alternatives in CLL therapy: managing adverse
      events.
AB  - Chronic lymphocytic leukemia (CLL) is a B-cell leukemia mainly affecting older
      adults. Historically, CLL has been regarded as an incurable disease, and
      treatment has been confined to cytotoxic chemotherapy regimens. However,
      prognosis for patients treated with these agents remained poor, prompting the
      development of new, targeted agents. The introduction of rituximab, a CD20
      targeted monoclonal antibody, revolutionized the treatment for this disease.
      Rituximab in combination with fludarabine improved response rates and length of
      progression-free survival. The success of rituximab in this setting has prompted
      the development of many more investigational agents for CLL, including other
      antibody agents. However, as with any medication, the potential benefit achieved
      with CLL therapies is mitigated by the safety risk for the patient. These agents
      have been associated with adverse events such as immunosuppression, reactivation
      of cytomegalovirus, and infusion-related reactions that can occur with antibody
      administration. Adverse events can greatly affect the patient's quality of life
      and ability to tolerate therapy. Management of adverse events is a critical
      component of the overall treatment strategy for CLL, particularly in elderly
      patients. In this clinical roundtable monograph, 3 expert physicians discuss the
      latest clinical studies evaluating the treatment of CLL, focusing on the adverse
      events associated with each agent and the potential interventions that can be
      used to manage their occurrence.

PMID- 21192631
TI  - Investigating inner-sphere reorganization via secondary kinetic isotope effects
      in the C-H cleavage reaction catalyzed by soybean lipoxygenase: tunneling in the
      substrate backbone as well as the transferred hydrogen.
AB  - This work describes the application of NMR to the measurement of secondary
      deuterium (2 degrees  (2)H) and carbon-13 ((13)C) kinetic isotope effects (KIEs)
      at positions 9-13 within the substrate linoleic acid (LA) of soybean lipoxygenase
      1. The KIEs have been measured using LA labeled with either protium (11,11-h2-LA)
      or deuterium (11,11-d2-LA) at the reactive C11 position, which has been
      previously shown to yield a primary deuterium isotope effect of ca. 80. The
      conditions of measurement yield the intrinsic 2 degrees  (2)H and (13)C KIEs on
      k(cat)/K(m) directly for 11,11-d2-LA, whereas the values for the 2 degrees  (2)H
      KIEs for 11,11-h2-LA are obtained after correction for a kinetic commitment. The
      pattern of the resulting 2 degrees  (2)H and (13)C isotope effects reveals values
      that lie far above those predicted from changes in local force constants.
      Additionally, many of the experimental values cannot be modeled by electronic
      effects, torsional strain, or the simple inclusion of a tunneling correction to
      the rate. Although previous studies have shown the importance of extensive
      tunneling for cleavage of the primary hydrogen at C11 of LA, the present findings
      can only be interpreted by extending the conclusion of nonclassical behavior to
      the secondary hydrogens and carbons that flank the position undergoing C-H bond
      cleavage. A quantum mechanical method introduced by Buhks et al. [J. Phys. Chem.
      1981, 85, 3763] to model the inner-sphere reorganization that accompanies
      electron transfer has been shown to be able to reproduce the scale of the 2
      degrees  (2)H KIEs.

PMID- 21192632
TI  - Visible-light photoredox catalysis: dehalogenation of vicinal dibromo-, alpha
      halo-, and alpha,alpha-dibromocarbonyl compounds.
AB  - vic-Dibromo-, alpha-halo-, or alpha,alpha-dibromocarbonyl compounds can be
      efficiently dehalogenated using catalytic tris(2,2'-bipyridyl)ruthenium
      dichloride (Ru(bpy)(3)Cl(2)) in combination with 1,5-dimethoxynaphthalene (DMN)
      and ascorbate as sacrificial electron donor. For this process, a visible light
      promoted photocatalytic cycle is proposed that involves the reduction of carbon
      halogen bonds via free radical intermediates.

PMID- 21192633
TI  - Regioselective inversion of the hydroxyl group in D-ribo-phytosphingosine via a
      cyclic sulfate and bis-sulfonate intermediate.
AB  - The selective synthesis of D-xylo- and D-lyxo-phytosphingosines from commercially
      available D-ribo-phytosphingosine is described. Thermolysis of the N-carbonyl
      protected cyclic sulfate led to an inversion of configuration of the proximal
      hydroxyl group to give the xylo-isomer, whereas the corresponding bis-sulfonate
      resulted in an inversion of configuration of the distal hydroxyl group to give
      the lyxo-isomer. This study allowed the comparison between a cyclic sulfate and a
      bis-sulfonate in an intramolecular substitution reaction involving a carbonyl
      oxygen nucleophile.

PMID- 21192634
TI  - Solubilization of a membrane protein by combinatorial supercharging.
AB  - Hydrophobic and aggregation-prone, membrane proteins often prove too insoluble
      for conventional in vitro biochemical studies. To engineer soluble variants of
      human caveolin-1, a phage-displayed library of caveolin variants targeted the
      hydrophobic intramembrane domain with substitutions to charged residues. Anti
      selections for insolubility removed hydrophobic variants, and positive selections
      for binding to the known caveolin ligand HIV gp41 isolated functional, folded
      variants. Assays with several caveolin binding partners demonstrated the
      successful folding and functionality by a solubilized, full-length caveolin
      variant selected from the library. This caveolin variant allowed assay of the
      direct interaction between caveolin and cavin. Clustered along one face of a
      putative helix, the solubilizing mutations suggest a structural model for the
      intramembrane domain of caveolin. The approach provides a potentially general
      method for solubilization and engineering of membrane-associated proteins by
      phage display.

PMID- 21192635
TI  - Doubly and triply linked porphyrin-perylene monoimides as near IR dyes with large
      dipole moments and high photostability.
AB  - Doubly and triply linked porphyrin-perylene monoimides 3 and 4, with
      extraordinary stability, large dipole moments, and strong near IR absorption,
      were prepared by means of one-pot oxidative cyclodehydrogenation promoted by
      FeCl(3).

PMID- 21192636
TI  - High-resolution visualization of fibrinogen molecules and fibrin fibers with
      atomic force microscopy.
AB  - We report an atomic force microscopy (AFM) study of fibrinogen molecules and
      fibrin fibers with resolution previously achieved only in few electron microscopy
      images. Not only are all objects triads, but the peripheral D regions are
      resolved into the two subdomains, apparently corresponding to the betaC and
      gammaC domains. The conformational analysis of a large population of fibrinogen
      molecules on mica revealed the two most energetically favorable conformations
      characterized by bending angles of ~100 and 160 degrees. Computer modeling of the
      experimental images of fibrinogen molecules showed that the AFM patterns are in
      good agreement with the molecular dimensions and shapes detected by other
      methods. Imaging in different environments supports the expected hydration of the
      fibrinogen molecules in buffer, whereas imaging in humid air suggests the 2D
      spreading of fibrinogen on mica induced by an adsorbed water layer. Visualization
      of intact hydrated fibrin fibers showed cross-striations with an axial period of
      24.0 +/- 1.6 nm, in agreement with a pattern detected earlier with electron
      microscopy and small-angle X-ray diffraction. However, this order is clearly
      detected on the surface of thin fibers and becomes less discernible with the
      fiber's growth. This structural change is consistent with the proposal that
      thinner fibers are denser than thicker ones, that is, that the molecule packing
      decreases with the increasing of the fibers' diameter.

PMID- 21192637
TI  - Intramolecular charge-transfer-induced decomposition promoted by an aprotic polar
      solvent for bicyclic dioxetanes bearing a 4-(benzothiazol-2-yl)-3-hydroxyphenyl
      moiety.
AB  - Bicyclic dioxetanes 3a-d bearing a 4-(benzothiazol-2-yl)-3-hydroxyphenyl group
      decomposed to give the corresponding keto esters 4a-d accompanied by the emission
      of bright light when simply dissolved in an aprotic polar solvent such as N
      methylpyrrolidone (NMP) or DMF at 50-100  degrees C. This solvent-promoted
      decomposition (SPD) was effectively a chemiluminescence process caused by the
      hydrogen bonding of a phenolic OH with a solvent molecule(s). The characteristics
      of the chemiluminescence in SPD resembled those in base-induced decomposition
      (BID), which occurs through an oxidoaryl-substituted dioxetane 5 by an
      intramolecular charge-transfer-induced decomposition (CTID) mechanism. Both free
      energies of activation, DeltaG(doubledagger)(SPD) and DeltaG(doubledagger)(BID),
      increased in the order 3a < 3b < 3c < 3d, and were linearly correlated with each
      other. However, SPD showed features different from those of BID in terms of
      enthalpy of activation and entropy of activation. SPD had large negative values
      for DeltaS(doubledagger) (ca. -71 J mol(-1) K(-1)) regardless of the substituent
      R at the 5-position for 3a-d, while the DeltaS(doubledagger) values for BID
      changed from 0.5 to -22 J mol(-1) K(-1) as R became smaller. The enthalpy of
      activation DeltaH(doubledagger) for SPD was 14-21 kJ mol(-1) smaller than that
      for BID.

PMID- 21192638
TI  - Synthesis of N2-alkyl-8-oxo-7,8-dihydro-2'-deoxyguanosine derivatives and effects
      of these modifications on RNA duplex stability.
AB  - N(2)-alkyl analogues of 8-oxo-7,8-dihydro-2'-deoxyguanosine (OG) were synthesized
      (alkyl = propyl, benzyl) via reductive amination of the protected OG nucleoside
      and incorporated into various positions of an RNA strand. Thermal stability
      studies of duplexes containing A or C opposite a single modified base revealed
      only moderate destabilization. Both OG as well as its N(2)-alkyl analogues can
      pair opposite A or C with nearly equal stability, potentially offering a new
      means of modulating RNA-protein interactions in the minor vs major grooves.

PMID- 21192639
TI  - Partially quarternized amino functional poly(methacrylate) terpolymers: versatile
      drug permeability modifiers.
AB  - Partially quarternized poly(methacrylate) terpolymers (Q-BBMCs) have been
      synthesized, based on the basic butylated methacrylate copolymer (BBMC/EUDRAGIT
      E), an excipient approved by the Food and Drug Administration (FDA) and to date
      mainly applied for tablet coatings. Via straightforward polymer modification
      reactions, a series of Q-BBMCs with quarternization degrees of 22%, 42%, and 65%
      has been prepared. Apical to basolateral transport across Caco-2 cell monolayers
      was investigated, employing the paracellular transported compounds trospium and
      mannitol. At pH 6.5 quarternization resulted in increased permeation enhancement
      up to 2.8-fold compared to BBMC, that is, up to 7.3-fold compared to control.
      Moreover, measurements of the transepithelial electrical resistance (TEER)
      revealed a special advantage of the quarternized poly(methacrylate) terpolymers
      with respect to the pH range, in which the polymers exhibit biological activity
      as permeation enhancers. Whereas at pH 6.5 TEER dropped within 30 min below 30%
      of the initial value for all polymers, at pH 7.4 this effect solely occurred for
      Q-BBMCs, meaning a significant extension of the pH range relevant for drug
      permeation. In a subsequent period of 6 h, also excellent recovery was observed.

PMID- 21192640
TI  - Self-assembly of elastin-based peptides into the ECM: the importance of integrins
      and the elastin binding protein in elastic fiber assembly.
AB  - The formation of a suitable extracellular matrix (ECM) that promotes cell
      adhesion, organization, and proliferation is essential within biomaterial
      scaffolds for tissue engineering applications. In this work, short elastin
      mimetic peptide sequences, EM-19 and EM-23, were engineered to mimic the active
      motifs of human elastin in hopes that they can stimulate ECM development in
      synthetic polymer scaffolds. Each peptide was incubated with human aortic smooth
      muscle cells (SMCs) and elastin and desmosine production were quantified after 48
      h. EM-19 inhibited elastin production through competitive binding phenomena with
      the elastin binding protein (EBP), whereas EM-23, which contains an RGDS domain,
      induces recovery of elastin production at higher concentrations, alluding to a
      higher binding affinity for the integrins than for the EBP and the involvement of
      integrins in elastin production. Colocalization of each peptide with the elastin
      matrix was confirmed using immunofluorescent techniques. Our data suggest that
      with appropriate cell-binding motifs, we can simulate the cross-linking of
      tropoelastin into the developing elastin matrix using short peptide sequences.
      The potential for increased cell adhesion and the incorporation of elastin chains
      into tissue engineering scaffolds make these peptides attractive bioactive
      moieties that can easily be incorporated into synthetic biomaterials to induce
      ECM formation.

PMID- 21192641
TI  - Artificial mixed-linked beta-glucans produced by glycosynthase-catalyzed
      polymerization: tuning morphology and degree of polymerization.
AB  - The glycosynthase derived from Bacillus licheniformis 1,3-1,4-beta-glucanase was
      able to polymerize glycosyl fluoride donors (G4)(m)G3GalphaF (m = 0-2, G =
      Glcbeta) leading to artificial mixed-linked beta-glucans with regular sequences
      and variable beta1,3 to beta1,4 linkage ratios. With the E134A glycosynthase
      mutant, polymers had average molecular masses (M(w)) of 10-15 kDa. Whereas
      polymer 2 ([4G4G3G](n)) was an amorphous precipitate, the water-insoluble
      polymers 1 ([4G3G](n)) and 3 ([4G4G4G3G](n)) formed spherulites of 10-20 MUm
      diameter. With the more active E134S glycosynthase mutant, polymerization led to
      high molecular mass polysaccharides, where M(w) was linearly dependent on enzyme
      concentration. Remarkably, a homo-polysaccharide [4G4G4G3G](n) with M(w) as high
      as 30.5 kDa (n ~ 47) was obtained, which contained a small fraction of products
      up to 70 kDa, a value that is in the range of the molecular masses of low
      viscosity cereal 1,3-1,4-beta-glucans, and among the largest products produced by
      a glycosynthase. Access to a range of novel tailor-made beta-glucans through the
      glycosynthase technology will allow to evaluate the implications of
      polysaccharide fine structures in their physicochemical properties and their
      applications as biomaterials, as well as to provide valuable tools for
      biochemical characterization of beta-glucan degrading enzymes and binding
      modules.

PMID- 21192642
TI  - Enantioselective organocatalytic Biginelli reaction: dependence of the catalyst
      on sterics, hydrogen bonding, and reinforced chirality.
AB  - From a systematic investigation involving the synthesis of a series of catalysts
      and screening studies, the organocatalyst 16, which is sterically hindered,
      contains a strong hydrogen-bonding site, and is endowed with reinforced
      chirality, is shown to promote the Biginelli cyclocondensation of aromatic as
      well as aliphatic aldehydes with ethyl acetoacetate and urea in a remarkably high
      enantioselectivity (ee ca. 94-99%).

PMID- 21192643
TI  - Effect of soil wetting and drying cycles on metolachlor fate in soil applied as a
      commercial or controlled-release formulation.
AB  - A controlled-release formulation (CRF) has been developed for metolachlor, which
      reduced its leaching in a sandy soil and improved weed control in comparison with
      the commercial formulation. The current study tested the effect of soil wetting
      and drying cycles (WDCs) on metolachlor fate (desorption, leaching, and weed
      control) applied as the CRF and as the commercial formulation. Metolachlor
      adsorption to a heavy soil (Terra-Rosa) was predominately to the clay minerals
      and oxides. Metolachlor release from a heavy soil subjected to WDCs was higher
      than its release from the soil not subjected to WDCs. Consequently, a bioassay in
      soil columns treated with the commercial formulation indicated enhanced
      metolachlor leaching in heavy soils under WDCs. In contrast, when metolachlor was
      applied as the CRF, leaching was suppressed and not affected by WDCs. These
      results emphasize the advantages of the CRF also in heavy soils subjected to
      WDCs.

PMID- 21192645
TI  - [4 + 3] Cycloaddition of aromatic alpha,beta-unsaturated aldehydes and ketones
      with epoxides: one-step approach to synthesize seven-membered oxacycles catalyzed
      by Lewis acid.
AB  - A novel intermolecular [4 + 3] cycloaddition method to construct 1,4-dioxide
      seven-membered oxacycles was developed. This one-step method was carried out in
      the presence of catalytic amount of (C(2)H(5))(2)OBF(3) under mild conditions.
      Seven-membered oxacycles and some natural compounds could be easily synthesized
      via this protocol. Control experiments were carried out and possible mechanism
      for the reaction was proposed. Asymmetric reactions were proceeded and 3e was
      obtained with moderate ee value.

PMID- 21192644
TI  - Reactive iron carbonyl reagents via reaction of metal alkoxides with Fe(CO)5 or
      Fe2(CO)9: synthesis of cyclobutenediones via double carbonylation of alkynes.
AB  - Alkoxy bases such as t-BuOK react with Fe(CO)(5) to give reactive iron carbonyl
      intermediates that in turn react with alkynes at 70  degrees C in THF to give 1,2
      cyclobutenediones in 70-93% yields after CuCl(2).2H(2)O oxidation. A novel 1,2
      diacyloxyferrole derivative was isolated in the reaction of diphenylacetylene
      with Fe(CO)(5)/t-BuOK in the presence of acetyl chloride in contrast to the
      formation of a 1,4-diacyloxyferrole complex formed in the reaction using
      Fe(CO)(5)/Me(3)NO. The Fe(2)(CO)(9)/t-BuOK reagent system also converts the
      alkynes to corresponding cyclobutenediones in 63-90% yields under similar
      reaction conditions.

PMID- 21192646
TI  - Polyolefin-supported recoverable/reusable Cr(III)-salen catalysts.
AB  - The design of functional soluble polyolefins for use as supports for salen
      ligands and metal complexes is described. Examples and applications that use both
      polyisobutylene (PIB)- and polyethylene (PE(Olig))-bound recoverable/recyclable
      salen ligands/metal complexes are detailed. In the case of using PIB as a
      support, the polymer-bound complexes can be recovered through the use of latent
      biphasic or a thermomorphic mixed solvent systems. In the case of PE(Olig)
      supported complexes, the thermomorphic PE(Olig)-bound salen species can be
      dissolved in "hot" solvents and quantitatively recovered as solids upon cooling
      to room temperature. Both the PIB- and PE(Olig)-bound salen catalysts were shown
      to catalyze the ring-opening of epoxides with various nucleophiles. Both sorts of
      polyolefin-bound catalysts can be recycled and reused with no observed loss in
      activity. However, limitations of catalyst concentration make chiral versions of
      these complexes uncompetitive in comparison to conventional chiral salen
      catalysts that can be used in neat substrate at higher concentration to produce
      high enantioselectivity in the ring-opening products. The preparation of a PIB
      bound "half-salen" catalyst was also briefly examined.

PMID- 21192647
TI  - Chirality-induced conformational preferences in peptide-metal ion binding
      revealed by IR spectroscopy.
AB  - Chirality reversal of a residue in a peptide can change its mode of binding to a
      metal ion, as shown here experimentally by gas-phase IR spectroscopy of peptide
      metal ion complexes. The binding conformations of Li(+), Na(+), and H(+) with the
      LL and DL stereoisomers of PhePhe were compared through IR ion spectroscopy using
      the FELIX free-electron laser. For the DL isomer, both Li(+) and Na(+)
      exclusively coordinate to the amide O atom, the carboxyl O atom, and one of the
      aromatic rings (the OOR conformation), while for the LL isomer, a mixture of the
      OOR and NOR conformations was found. The stereochemically induced change in
      conformation is shown to reflect the strength of an NH...pi interaction remote
      from the metal ion site. Protonated PhePhe shows no stereochemically induced
      variation in binding geometry.

PMID- 21192648
TI  - An enantioselective synthesis of (+)-polyoxamic acid via phase-transfer catalytic
      conjugate addition and asymmetric dihydroxylation.
AB  - A new enantioselective synthetic method of (+)-polyoxamic acid is reported. (+)
      Polyoxamic acid could be obtained in 7 steps with 46% overall yield from
      diphenylmethyl-glycineimine tert-butyl ester via an enantioselective phase
      transfer conjugate addition (99% yield, 96% ee) and an asymmetric dihydroxylation
      (98% yield, 94% de) as the key reactions.

PMID- 21192649
TI  - Miscibility and multilayer formation of fluoroalkane-alpha,omega-diol mixtures at
      the air/water interface.
AB  - The surface tension gamma of the aqueous solution of 1H,1H,6H,6H-perfluorohexane
      1,6-diol (FC6diol) and 1H,1H,8H,8H-perfluorooctane-1,8-diol (FC8diol) mixtures
      was measured as a function of total molality m and composition of FC8diol in the
      mixture X2 at 293.15 K under atmospheric pressure. The gamma vs m curves except
      at X2 = 0 and 0.05 have a distinct break point due to a phase transition in the
      adsorbed film. The surface pressure pi vs mean area per adsorbed molecule A
      curves consist of two parts connected by a discontinuous change. The curve was
      almost vertical just below the phase transition, and the variation of the A value
      with film composition X(2)(H) was linear corresponding to the fact that FC6diol
      and FC8diol molecules orient parallel to the surface and are densely packed with
      the same areas of individual condensed films. Above the phase transition, the A
      value further decreases to around 0.12-0.19 nm2 which is much smaller than the
      cross-sectional area of the fluorocarbon chain, indicating the multilayer
      formation at the surface. The phase diagram of adsorption (PDA) in the condensed
      film showed that the m vs film composition X(2)(H) curve is almost linear and the
      excess Gibbs energy of adsorption g(HE)/RT is at most 0.01, manifesting the ideal
      mixing of molecules. This is in contrast to a positive deviation (g(HE)/RT ~0.12)
      observed in the condensed film of the mixture of 1H,1H,2H,2H-perfluorodecanol
      (FC10OH) and 1H,1H,2H,2H-perfluorododecanol (FC12OH) with perpendicular molecular
      orientation. The loss of dispersion interaction between different species having
      different chain lengths is more appreciable in the perpendicular condensed films
      and thus leads to less miscibility of FC10OH and FC12OH. In the parallel
      condensed film, on the other hand, FC6diol and FC8diol molecules can arrange
      their position as close as possible to minimize the loss of dispersion
      interaction. The X(2)(H) value in the multilayer is close to unity, and thus, the
      multilayer consists of almost FC8diol molecules which form a multilayer in the
      single-component system. Furthermore, the condensed monolayer-multilayer phase
      transition was accompanied by a large increase in surface density of FC8diol and
      a small decrease in that of FC6diol, indicating that FC8diol molecules pile
      preferentially to form a multilayer.

PMID- 21192651
TI  - Doubly activated supramolecular reaction: transesterification of acyclic
      oligoether esters with metal alkoxides.
AB  - Transesterification reactions of acyclic oligoether esters E3-E10 with metal
      alkoxides were accelerated upon noncovalent complexation of the esters with metal
      ions. In the reaction of monovalent alkaline metal alkoxides, CH(3)ONa and
      CH(3)OK, plots of the observed rate constants k(obs) with respect to the chain
      length of E3-E10 showed selective acceleration of the transesterification.
      Compared with the shortest E3, which can hardly bind metal ion, 4.3- and 6.6-fold
      accelerations in the maxima were achieved in the combinations of E5/CH(3)ONa and
      E6/CH(3)OK, respectively. Supramolecular intermediate complex could be
      spectrometrically visualized by ESI-FT-ICR-MS in the course of reaction. Kinetic
      experiments, together with structural analyses by means of NMR, mass
      spectrometry, and DFT calculations of the intermediate complexes, indicate that a
      size-fit complex of host substitute with alkali metal ion allows strong electron
      withdrawing due to the close contact of the carbonyl oxygen to the metal ion,
      resulting in the selective rate enhancement of the reaction, while in the
      reaction of E3-E10 with a divalent alkaline earth metal alkoxide,
      (CH(3)CH(2)O)(2)Ba, the k(obs) values increased stepwise with elongation of the
      side arm to attain an dramatic large acceleration. In comparison with the k(obs)
      of E3, 4610-fold acceleration was achieved in the reaction of E10. The double
      activation of the host substrate and guest counter nucleophile at once brings
      about this extraordinary rate acceleration. The strong wrapping complexation of
      long oligoether ester with barium ethoxide allows for the effective electron
      withdrawal from the ester carbonyl group (host activation) as well as separation
      of the accompanying guest alkoxide anions (guest activation).

PMID- 21192650
TI  - Oxidation of organotrifluoroborates via oxone.
AB  - A method for the oxidation of organotrifluoroborates using Oxone was developed. A
      variety of aryl-, heteroaryl-, alkenyl-, and alkyltrifluoroborates were converted
      into the corresponding oxidized products in excellent yields. This method proved
      to be tolerant of a broad range of functional groups, and in secondary alkyl
      substrates it was demonstrated to be completely stereospecific.

PMID- 21192652
TI  - Palladium-catalyzed indole, pyrrole, and furan arylation by aryl chlorides.
AB  - The palladium-catalyzed direct arylation of indoles, pyrroles, and furans by aryl
      chlorides has been demonstrated. The method employs a palladium acetate catalyst,
      2-(dicyclohexylphosphino)-biphenyl ligand, and an inorganic base. Electron-rich
      and electron-poor aryl chlorides as well as chloropyridine coupling partners can
      be used, and arylated heterocycles are obtained in moderate to good yields.
      Optimization of base, ligand, and solvent is required for achieving best results.

PMID- 21192653
TI  - Asymmetric synthesis of 1,2,9,9a-tetrahydrocyclopropa[c]benzo[e]indol-4-one
      (CBI).
AB  - A short, asymmetric synthesis of the 1,2,9,9a
      tetrahydrocyclopropa[c]benzo[e]indol-4-one (CBI) analogue of the CC-1065 and
      duocarmycin DNA alkylation subunits is described. Treatment of iodo-epoxide 5,
      prepared by late-stage alkylation of 4 with (S)-glycidal-3-nosylate, with EtMgBr
      at room temperature directly provides the optically pure alcohol 6 in 87% yield
      (99% ee) derived from selective metal-halogen exchange and subsequent
      regioselective intramolecular 6-endo-tet cyclization. The use of MeMgBr or i
      PrMgBr also provides the product in high yields (82-87%), but requires larger
      amounts of the Grignard reagent to effect metal-halogen exchange and cyclization.
      Direct transannular spirocyclization of 7 following O-debenzylation of 6 provides
      N-Boc-CBI. This approach represents the most efficient (9-steps, 31% overall) and
      effective (99% ee) route to the optically pure CBI alkylation subunit yet
      described.

PMID- 21192654
TI  - Molecular mechanism by which palmitate inhibits PKR autophosphorylation.
AB  - PKR (double-stranded RNA-activated protein kinase) is an important component of
      the innate immunity, antiviral, and apoptotic pathways. Recently, our group found
      that palmitate, a saturated fatty acid, is involved in apoptosis by reducing the
      autophosphorylation of PKR at the Thr451 residue; however, the molecular
      mechanism by which palmitate reduces PKR autophosphorylation is not known. Thus,
      we investigated how palmitate affects the phosphorylation of the PKR protein at
      the molecular and biophysical levels. Biochemical and computational studies show
      that palmitate binds to PKR, near the ATP-binding site, thereby inhibiting its
      autophosphorylation at Thr451 and Thr446. Mutation studies suggest that Lys296
      and Asp432 in the ATP-binding site on the PKR protein are important for palmitate
      binding. We further confirmed that palmitate also interacts with other kinases,
      due to the conserved ATP-binding site. A better understanding of how palmitate
      interacts with the PKR protein, as well as other kinases, could shed light onto
      possible mechanisms by which palmitate mediates kinase signaling pathways that
      could have implications on the efficacy of current drug therapies that target
      kinases.

PMID- 21192655
TI  - Dehydro[12]annulenes: structures, energetics, and dynamic processes.
AB  - Density functional and coupled cluster calculations on neutral
      monodehydro[12]annulenes (C(12)H(10)) reveal a global minimum that should be
      kinetically stable. At the CCSD(T)/cc-pVDZ//BHLYP/6-31G* level, the unsymmetrical
      CTCTC conformer 1a lies at least 3 kcal/mol below all other isomers studied. The
      two isomers closest in energy to 1a are Mobius structure 5a (CCTCC) and all-cis
      6a. Isomer 1a can undergo conformational automerization with E(a) = 3.9 kcal/mol,
      implying that this process would be rapid on the NMR time scale, and computed
      (1)H NMR parameters (GIAO-B3LYP/6-311+G**//RHF/6-31G*) are presented. Cumulenic
      dehydro[12]annulene isomers, with 1,2,3-butatriene subunits, were found to be
      reactive intermediates in the interconversion of different configurations of the
      alkyne forms. Pathways for configuration change of 1a, and for subsequent
      rearrangement to biphenyl, were investigated. The 28 kcal/mol overall barrier for
      the lowest energy pathway connecting 1a to biphenyl suggests that 1a is
      kinetically stable with respect to valence isomerization.

PMID- 21192656
TI  - Mercury(II)-mediated cleavage of cyclopropylcarbinols by an intramolecular
      sulfinyl group as a stereo- and regioselective route to stereotriads and
      stereotetrads.
AB  - Mercury(II) salt mediated opening of cyclopropylcarbinols by an intramolecular
      sulfinyl group is disclosed. All four diastereomeric stereotriads have been
      prepared from cis- and trans-disubstituted cyclopropanes. The trisubstituted
      cyclopropanes also react regio- and stereoselectively to afford products
      possessing quaternary stereogenic centers. The reaction is clean and general.

PMID- 21192657
TI  - Tuning the structure and the magnetic properties of metallo-supramolecular
      polyelectrolyte-amphiphile complexes.
AB  - Self-assembly of Fe(2+) ions and the rigid ditopic ligand 1,4-bis(2,2':6',2''
      terpyridin-4'-yl)benzene results in metallo-supramolecular coordination
      polyelectrolytes (MEPE). Sequential self-assembly of MEPE and dialkyl phosphoric
      acid esters of varying chain length via electrostatic interactions leads to the
      corresponding polyelectrolyte-amphiphile complexes (PAC), which have liquid
      crystalline properties. The PACs have a stratified architecture where the MEPE is
      embedded in between the amphiphile layers. Upon heating above room temperature,
      the PACs show either a reversible or an irreversible spin-crossover (SCO) in a
      temperature range from 360 to 460 K depending on the architecture of the
      amphiphilic matrix. As the number of amphiphiles per metal ion is increased in
      the sequence 1:2, 1:4, and 1:6, the temperature of the SCO is shifted to higher
      values whereas the amphiphile chain length does not have a significant impact on
      the SCO temperature. In summary, we describe in this article how the structure
      and the magnetic response function of PACs can be tailored through the design of
      the ligand and the composition. To investigate the structure and the magnetic
      behavior, we use X-ray scattering, X-ray absorption spectroscopy, differential
      scanning calorimetry, faraday-balance, and superconducting quantum interference
      measurements in combination with molecular modeling.

PMID- 21192659
TI  - A practical use of ligand efficiency indices out of the fragment-based approach:
      ligand efficiency-guided lead identification of soluble epoxide hydrolase
      inhibitors.
AB  - Ligand efficiency is frequently used to evaluate fragment compounds in fragment
      based drug discovery. We applied ligand efficiency indices in a conventional
      virtual screening-initiated lead generation study of soluble epoxide hydrolase
      inhibitors. From a considerable number of screening hits, we carefully selected a
      compound exhibiting relatively weak inhibitory activity but high ligand
      efficiency. This ligand efficiency-guided selection could reveal compounds
      possessing preferable lead-like characteristics in terms of molecular size and
      lipophilicity. The following hit-to-lead medicinal chemistry campaign
      successfully led to a more potent, ADMET-clean, lead-like compound preserving
      high ligand efficiency. Retrospective analyses, including consideration of the
      more recently proposed indices of ligand efficiency, shed light on the validity
      of our hit triage and hit-to-lead studies. The present work proposes a practical
      methodology for lead generation using the concept of ligand efficiency.

PMID- 21192658
TI  - Capillary isoelectric focusing of individual mitochondria.
AB  - Mitochondria are highly heterogeneous organelles that likely have unique
      isoelectric points (pI), which are related to their surface compositions and
      could be exploited in their purification and isolation. Previous methods to
      determine pI of mitochondria report an average pI. This article is the first
      report of the determination of the isoelectric points of individual mitochondria
      by capillary isoelectric focusing (cIEF). In this method, mitochondria labeled
      with the mitochondrial-specific probe 10-N-nonyl acridine orange (NAO) are
      injected into a fused-silica capillary in a solution of carrier ampholytes at
      physiological pH and osmolarity, where they are focused then chemically mobilized
      and detected by laser-induced fluorescence (LIF). Fluorescein-derived pI markers
      are used as internal standards to assign a pI value to each individually detected
      mitochondrial event, and a mitochondrial pI distribution is determined. This
      method provides reproducible distributions of individual mitochondrial pI,
      accurate determination of the pI of individual mitochondria by the use of
      internal standards, and resolution of 0.03 pH units between individual
      mitochondria. This method could also be applied to investigate or design
      separations of organelle subtypes (e.g., subsarcolemmal and interfibrillar
      skeletal muscle mitochondria) and to determine the pIs of other biological or
      nonbiological particles.

PMID- 21192660
TI  - Monoprotic mineral acids analyzed by the smaller-ion shell model of strong
      electrolyte solutions.
AB  - The smaller-ion shell (SiS) model of strong binary electrolyte solutions extends
      the Debye-Huckel theory to the case of ions of unequal size; it is effective for
      many electrolytes of the various families in water at 25  degrees C up to
      moderate concentrations, with ion-size parameters (ISPs) of co-ions being equal
      to the ionic diameters, and with a varying degree of ISP additivity. A SiS
      analysis is now provided for aqueous solutions of the acids HCl, HBr, HI, and
      HClO(4) at 25  degrees C; theory fits very well with experiment when the mean
      effective ionic diameter of the proton (H(3)O(+)) is chosen as ~1.1 A and the
      mean anion size is the corresponding crystallographic diameter, as with other
      electrolytes having the same anion. The ISP nonadditivity is positive and large,
      apparently reflecting a strong polarizing effect of the small proton on the large
      anion. The SiS-derived single-ion activity coefficients of the proton allow
      calculation of the pH of the acids, and reliable values are obtained below the
      known limit of pH ~ 2, i.e., smaller and even negative values. The computed pH
      compares well with the experimentally derived Hammett acidity function, H(0), up
      to moderate concentration; differences between the two functions at higher
      concentration shed light on the activity coefficients of Hammett indicators and
      their response to increasing acid strength.

PMID- 21192661
TI  - Low-temperature plasma ionization ion mobility spectrometry.
AB  - In this research work, the capability of low-temperature plasma (LTP) as an
      ionization source for ion mobility spectrometry (IMS) has been investigated for
      the first time. This new ionization source enhances the potential of IMS as a
      portable analytical tool and allows direct analysis of various chemical compounds
      without having to evaporate the analyte or seek a solvent or reagent whatsoever.
      The effects of parameters such as the flow rate of the discharge gas, plasma
      voltage, and positioning of the LTP on the IMS signal were investigated. The
      positive reactant ions generated by the LTP ionization source were similar to
      those created in a corona discharge ionization source, where the proton clusters
      ((H(2)O)(n)H(+)) are the most abundant reactant ion, and in the negative mode, in
      addition to a saturated electron peak, several negative reactant ions (e.g.,
      NO(x)(-)) were observed too. These reactant ions subsequently ionized the gaseous
      samples directly and liquids or solids after evaporation by plasma desorption.
      The ion mobility spectra of a few selected compounds, including explosives,
      drugs, and amines, were obtained to evaluate the new ionization source in
      positive and negative modes, and the reduced mobility values (K(0)) of the
      originated ions were calculated. Furthermore, the method has also been applied to
      obtain the figures of merit for acetaminophen as a test compound. The results
      obtained are promising enough to ensure the use of LTP as a desorption/ionization
      source in IMS for analytical applications.

PMID- 21192662
TI  - Tandem mass spectrometry for the direct assay of lysosomal enzymes in dried blood
      spots: application to screening newborns for mucopolysaccharidosis II (Hunter
      Syndrome).
AB  - We have developed a tandem mass spectrometry based assay of iduronate-2-sulfatase
      (IdS) activity for the neonatal detection of mucopolysaccharidosis II (MPS-II,
      Hunter Syndrome). The assay uses a newly designed synthetic substrate (IdS-S)
      consisting of alpha-L-iduronate-2-sulfate, which is glycosidically conjugated to
      a coumarin and a linker containing a tert-butyloxycarbamido group. A short
      synthesis of the substrate has been developed that has the potential of being
      scaled to multigram quantities. Sulfate hydrolysis of IdS-S by IdS found within a
      3 mm dried blood spot specifically produces a nonsulfated product (IdS-P) which
      is detected by electrospray tandem mass spectrometry and quantified using a
      deuterium-labeled internal standard, both carried out in positive ion mode.
      Analysis of DBS from 75 random human newborns showed IdS activities in the range
      of 4.8-16.2 (mean 9.1) MUmol/(h L of blood), which were clearly distinguished
      from the activities measured for 14 MPS-II patients at 0.17-0.52 (mean 0.29)
      MUmol/(h L of blood). The assay shows low blank activity, 0.15 +/- 0.03 MUmol/(h
      L of blood). The within-assay coefficient of variation (CV) was 3.1% while the
      interassay CV was 15%.

PMID- 21192663
TI  - Polyazetidine-coated microelectrodes: electrochemical and diffusion
      characterization of different redox substrates.
AB  - The present paper reports on the diffusion characteristics and electron transfer
      properties of a membrane obtained from polyazetidine prepolymer (PAP) consisting
      of repeating units of 1-(aminomethyl)-1-{2-[(6-oxyhexane)amino]ethyl}-3
      hydroxyazetidinium chloride studied in the presence of seven simple redox
      electroactive molecules: ABTS, catechol, dopamine, ferrocenecarboxylic acid,
      ferricyanide, ferrocyanide, and the osmium complex bis(2,2-bipyridyl)-4
      aminomethylpyridine chloride hexafluorophosphate (Os[(bpy)(2) 4-AMP Cl](+)).
      Using water as medium, the apparent diffusion coefficients (D(app)), the
      concentrations of the compounds in the membrane, and the heterogeneous rate
      constants (k(s)) were calculated as a function of temperature, and the influence
      thereof on these parameters was evaluated. Even if D(app) and k(s) values in the
      presence of PAP are smaller than in solution, this decrease is small enough to
      indicate that the PAP membrane shows excellent diffusion and electron-exchange
      properties with respect to other commonly used membranes reported in the
      literature.

PMID- 21192664
TI  - Molecular dynamics of potential rRNA binders: single-stranded nucleic acids and
      some analogues.
AB  - By hindering or "silencing" protein translation in vivo, antisense nucleic acid
      analogues that hybridize to bacterial rRNA could serve as a promising class of
      antibacterial compounds. Thus, we performed a comparative analysis of the
      dynamical properties of modified oligonucleotides based upon a sequence
      (5')r(UGUUACGACU)(3') that is complementary to bacterial ribosomal A-site RNA. In
      particular, 25 ns explicit solvent molecular dynamics simulations were computed
      for the following six single-stranded decamers: (1) the above RNA in unmodified
      form; (2) the 2'-O-methyl-modified RNA; (3) peptide nucleic acid (PNA) analogues
      of the above sequence, containing either (a) T or (b) U; and (4) two serine
      substituted PNAs. Our results show that 2'-O-methylation attenuates RNA backbone
      dynamics, thereby preventing interconversion between stacked and unstacked
      conformations. The PNA analogue is rendered less flexible by replacing uracil
      with thymine; in addition, we found that derivatizing the PNA backbone with
      serine leads to enhanced base-stacking interactions. Consistent with known
      solubility properties of these classes of molecules, both RNAs exhibited greater
      localization of water molecules than did PNA. In terms of counterions, the
      initially helical conformation of the 2'-O-methyl RNA exhibits the highest Na(+)
      density among all the simulated decamers, while Na(+) build-up was most
      negligible for the neutral PNA systems. Further studies of the conformational and
      physicochemical properties of such modified single-stranded oligomers may
      facilitate better design of nucleic acid analogues, particularly those capable of
      serving as specific, high-affinity ribosomal A-site binders.

PMID- 21192665
TI  - Total synthesis of natural and non-natural Delta(5,6)Delta(12,13)-jatrophane
      diterpenes and their evaluation as MDR modulators.
AB  - We report the details of the total synthesis of natural and non-natural jatropha
      5,12-dienes. The successful tactic for the assembly of the strained trans
      bicyclo[10.3.0]pentadecane scaffold employed a B-alkyl Suzuki-Miyaura cross
      coupling for the formation of the C5/C6 double bond and a ring-closing metathesis
      for the construction of the C12/C13 double bond. The key step of the synthesis of
      the cyclopentane fragment, an uncatalyzed intramolecular carbonyl-ene reaction,
      was studied computationally by DFT calculations. The members of the ensemble of
      synthetic natural and non-natural jatrophanes were subsequently examined as
      modulators for the ABCB1, ABCG2, and ABCC1 efflux proteins, which are associated
      with multidrug resistance in cancer chemotherapy.

PMID- 21192666
TI  - Metallic nanodot arrays by stencil lithography for plasmonic biosensing
      applications.
AB  - The fabrication of gold nanodots by stencil lithography and its application for
      optical biosensing based on localized surface plasmon resonance are presented.
      Arrays of 50-200 nm wide nanodots with different spacing of 50-300 nm are
      fabricated without any resist, etching, or lift-off process. The dimensions and
      morphology of the nanodots were characterized by scanning electron and atomic
      force microscopy. The fabricated nanodots showed localized surface plasmon
      resonance in their extinction spectra in the visible range. The resonance
      wavelength depends on the periodicity and dimensions of the nanodots. Bulk
      refractive index measurements and model biosensing of streptavidin were
      successfully performed based on the plasmon resonance shift induced by local
      refractive index change when biomolecules are adsorbed on the nanodots. These
      results demonstrate the potential of stencil lithography for the realization of
      plasmon-based biosensing devices.

PMID- 21192667
TI  - Nonpolymeric thermosensitive benzenetricarboxamides.
AB  - A new class of nonpolymeric thermosensitive materials based on the benzene-1,3,5
      tricarboxamide (BTC) structural platform are described. We observed that the
      benzocrown ether-substituted BTC derivatives undergo an unusual temperature
      dependent reversible solubility change in aqueous solution. Thus, a clear
      nonfluorescent solution of BTC derivatives becomes turbid and generates
      fluorescent aggregates above the LCST temperature. The aggregates disappear, and
      a clear solution is reformed when the solution is cooled to 20  degrees C. It is
      believed that the LCST behavior of BTC derivatives results from the removal of
      water molecules from crown ether moieties at elevated temperature. Thus, BTC
      derivatives exist in fully hydrated forms below the LCST. Heating the BTC
      derivatives solutions causes the expulsion of water and induces the formation of
      aggregates. At room temperature, the removal of water from BTC derivatives occurs
      slowly and leads to the formation of long nanofibers.

PMID- 21192668
TI  - Structure of the chromophore binding pocket in the Pr state of plant phytochrome
      phyA.
AB  - A homology structural model was generated for plant phytochrome phyA utilizing
      the crystal structure of the sensory module of cyanobacterial phytochrome Cph1
      (Cph1Delta2). As chromophores, either the native phytochromobilin cofactor
      (PPhiB) or phycocyanobilin (PCB), the natural cofactor in Cph1, was incorporated.
      These homology models were further optimized by molecular dynamics (MD)
      simulations revealing a satisfying overall agreement with the crystal structure
      of Cph1Delta2. Notable differences in the PPhiB adduct of phyA result from a
      restructuring of the small helical segment alpha(7) that leads to displacements
      of a few amino acids away from the cofactor. This repositioning of residues also
      include aspartate 218 such that, instead of its carbonyl function as in
      Cph1Delta2, an additional water molecule forms hydrogen bonds with the ring B and
      C NH groups. To validate the phyA structural model in the chromophore binding
      pocket, Raman spectra of the cofactor were calculated by means of the quantum
      mechanics/molecular mechanics (QM/MM) hybrid methodology and compared with the
      experimental resonance Raman (RR) spectra. The satisfactory overall agreement
      between calculated and experimental spectra is taken as an indication for the
      good quality of the structural model. Moreover, the methine bridge stretching
      modes and the effects of isotopic labeling at selected positions of the
      chromophore are very well reproduced to allow confirming even details of the
      methine bridge geometry as predicted by the homology model. Specifically, it is
      demonstrated that the experimental RR spectra are consistent with a torsional
      angle of ring D with respect to ring C that is distinctly higher for phyA-PCB (45
      degrees ) and phyA-PPhiB (42 degrees ) than for Cph1Delta2 (30 degrees ). Raman
      spectra calculated from different points of the MD trajectory display variations
      of the mode frequencies and intensities reflecting the structural fluctuations
      from snapshot to snapshot. The snapshot spectrum of the lowest energy structure
      and the sum of all snapshot spectra afford an equally good description of the
      experimental data. Particularly large variations between the snapshots are noted
      for the N-H in-plane bending mode of the pyrrole rings B and C, which reflect
      alterations of the hydrogen bond interactions brought about by fluctuations of
      water molecules in the cofactor cavity. This overestimation of the water molecule
      mobility is a consequence of the deficiency of the current QM/MM methodology
      that, due to the lack of appropriate protein force fields, cannot adequately
      account for the electrostatics in the cofactor pocket.

PMID- 21192670
TI  - Knowledge-based scoring functions in drug design: 2. Can the knowledge base be
      enriched?
AB  - Fast and accurate predicting of the binding affinities of large sets of diverse
      protein-ligand complexes is an important, yet extremely challenging, task in drug
      discovery. The development of knowledge-based scoring functions exploiting
      structural information of known protein-ligand complexes represents a valuable
      contribution to such a computational prediction. In this study, we report a
      scoring function named IPMF that integrates additional experimental binding
      affinity information into the extracted potentials, on the assumption that a
      scoring function with the "enriched" knowledge base may achieve increased
      accuracy in binding affinity prediction. In our approach, the functions and atom
      types of PMF04 were inherited to implicitly capture binding effects that are hard
      to model explicitly, and a novel iteration device was designed to gradually
      tailor the initial potentials. We evaluated the performance of the resultant IPMF
      with a diverse set of 219 protein-ligand complexes and compared it with seven
      scoring functions commonly used in computer-aided drug design, including GLIDE,
      AutoDock4, VINA, PLP, LUDI, PMF, and PMF04. While the IPMF is only moderately
      successful in ranking native or near native conformations, it yields the lowest
      mean error of 1.41 log K(i)/K(d) units from measured inhibition affinities and
      the highest Pearson's correlation coefficient of R(p)2 0.40 for the test set.
      These results corroborate our initial supposition about the role of "enriched"
      knowledge base. With the rapid growing volume of high-quality structural and
      interaction data in the public domain, this work marks a positive step toward
      improving the accuracy of knowledge-based scoring functions in binding affinity
      prediction.

PMID- 21192669
TI  - Complementary regioselectivity in the Cu(I)-catalyzed diamination of conjugated
      dienes to form cyclic sulfamides.
AB  - This paper describes the regioselective diamination of conjugated dienes using
      inexpensive Cu(I) as catalyst and N,N-di-tert-butylthiadiaziridine 1,1-dioxide as
      nitrogen source. The regioselectivity of diamination is likely due to dual
      mechanistic pathways which are greatly influenced by reaction conditions and the
      nature of the diene. A variety of useful internal and terminal cyclic sulfamides
      can be obtained in good yield.

PMID- 21192672
TI  - One-dimensional exciton diffusion in perylene bisimide aggregates.
AB  - The dynamics and mobility of excitons in J-aggregates of perylene bisimides are
      investigated by transient absorption spectroscopy with a time resolution of 50
      fs. The transient spectra are compatible with an exciton delocalization length of
      two monomers and indicate that vibrational and configurational relaxation
      processes are not relevant for the spectroscopic properties of the aggregates.
      Increasing the pump pulse energy and in that way the initial exciton density
      results in an accelerated signal decay and pronounced exciton-exciton
      annihilation dynamics. Modeling the data by assuming a diffusive exciton motion
      reveals that the excitons cannot migrate freely in all three directions of space
      but their mobility is restricted to one dimension. The observed anisotropy
      supports this picture and points against direct Forster-transfer-mediated
      annihilation between the excitons. A diffusion constant of 1.29 nm(2)/ps is
      deduced from the fitting procedure that corresponds to a maximal exciton
      diffusion length of 96 nm for the measured exciton lifetime of 3.6 ns. The
      findings indicate that J-aggregates of perylene bisimides are promising building
      blocks to facilitate directed energy transport in optoelectronic organic devices
      or artificial light-harvesting systems.

PMID- 21192671
TI  - Protein nanopatterns by oxime bond formation.
AB  - Patterning proteins on the nanoscale is important for applications in biology and
      medicine. As feature sizes are reduced, it is critical that immobilization
      strategies provide site-specific attachment of the biomolecules. In this study,
      oxime chemistry was exploited to conjugate proteins onto nanometer-sized
      features. Poly(Boc-aminooxy tetra(ethylene glycol) methacrylate) was synthesized
      by free radical polymerization. The polymer was patterned onto silicon wafers
      using an electron beam writer. Trifluoroacetic acid removal of the Boc groups
      provided the desired aminooxy functionality. In this manner, patterns of
      concentric squares and contiguous bowtie shapes were fabricated with 150-170-nm
      wide features. Ubiquitin modified at the N-terminus with an alpha-ketoamide group
      and N(epsilon)-levulinyl lysine-modified bovine serum albumin were subsequently
      conjugated to the polymer nanopatterns. Protein immobilization was confirmed by
      fluorescence microscopy. Control studies on protected surfaces and using proteins
      presaturated with O-methoxyamine indicated that attachment occurred via oxime
      bond formation.

PMID- 21192673
TI  - Controlling the morphology of rhodium nanocrystals by manipulating the growth
      kinetics with a syringe pump.
AB  - Noble-metal nanocrystals with well-defined and controllable morphologies are of
      great importance to applications in catalysis, plasmonics, and surface-enhanced
      spectroscopy. Many synthetic approaches have been demonstrated for controlling
      the growth habit and thus morphology of metal nanocrystals, but most of them are
      based on a thermodynamic approach, including the use of a capping agent. While
      thermodynamic control has shown its power in generating nanocrystals with a
      myriad of different morphologies, it is ultimately limited by the obligation to
      minimize the surface energy of a system. As a result, it is impractical to use
      thermodynamic control to generate nanocrystals having high-energy facets and/or a
      negative curvature. Using rhodium as an example, here we demonstrate a general
      method based on kinetic control with a syringe pump that can be potentially
      extended to other noble metals and even other solid materials. For the first
      time, we were able to produce concave nanocubes with a large fraction of {110}
      facets and octapods with a cubic symmetry in high yields by simply controlling
      the injection rate at which the precursor was added into the reaction solution.
      The concave nanocubes with {110} facets and a unique cavity structure on the
      surface are important for a variety of applications.

PMID- 21192674
TI  - Sensitive and spatially multiplexed detection system based on dielectrophoretic
      manipulation of DNA-encoded particles used as immunoreactions platform.
AB  - In this work, we designed a new immunodevice that combines competitive
      immunoreactions on the microparticles, accumulation of these particles by
      negative dielectrophoresis (n-DEP), and their subsequent capture through
      hybridization among single-stranded DNAs (ssDNAs). Two widely used pesticides,
      atrazine and bromopropylate, were used as target molecules to test the resulting
      simultaneous detection system. For sensing, we prepared two different sets of
      microparticles: one modified with atrazine-conjugated bovine serum albumin (BSA
      2d) and ssDNA-J1(up) and the other with bromopropylate-conjugated aminodextran
      (AD-155) and ssDNA-J2(up). The microparticles were incubated in a mixture of
      analyte-specific antibody and analyte at different concentrations to trap the
      unreacted antibodies prior to being labeled with antibodies conjugated with a
      fluorescence molecule. A suspension containing both types of microparticles was
      introduced into an n-DEP device consisting of an interdigitated microarray (IDA)
      electrode and channel modified with ssDNA-J1(down) and ssDNA-J2(down), which are
      complementary to ssDNA-J1(up) and ssDNA-J2(up), respectively. The n-DEP force
      generated by applying AC voltage to the IDA electrode displaced the
      microparticles toward the encoded areas, causing them to rapidly accumulate on
      the upper surfaces. Hybridization allowed us to distinguish the microparticles
      and sense multiple analytes by spatial recognition in the DNA-encoded areas. The
      fluorescence intensity of the captured particles, which depends on analyte
      concentrations, was measured selectively by focusing on specific areas. The
      strategy is advantageous for sensitivity due to the equivalent trapping
      efficiency by DNA hybridization and large surface area of the microparticle for
      immunoreactions. The rapidity and simplicity were still supported by particle
      manipulation. Using this concept, we detect atrazine and bromopropylate
      simultaneously with limits of detection (LODs) of 0.2 MUg.L(-1), which covered
      the maximum residue level (MRL) in food samples established the European Union
      (EU) and Japan Ministry of Health, Labor and Welfare (MHLW).

PMID- 21192675
TI  - Structural design of the active site for covalent attachment of the heme to the
      protein matrix: studies on a thermostable cytochrome P450.
AB  - The molecular basis of the post-translational modification involving covalent
      attachment of the heme with a glutamic acid observed in some enzymes of the CYP4
      family of heme monooxygenases has been investigated using site-directed
      mutagenesis of CYP175A1 from Thermus thermophilus. Earlier studies of CYP4 as
      well as the G248E mutant of CYP101A1 showed covalent linkage of the heme to a
      conserved glutamic acid of helix I. We have introduced Glu/Asp at the Leu80
      position in the beta-turn of CYP175A1, on the basis of molecular modeling
      studies, to assess whether formation of such a covalent linkage is limited only
      to helix I or whether such modification may also take place with the residue that
      is spatially located at a position appropriate for activation by the heme
      peroxidase reaction. Tandem mass spectrometry analyses of the tryptic digest of
      the wild type and mutants of CYP175A1 were conducted to identify any heme-bound
      peptide. Tryptic digestion of the L80E mutant of CYP175A1 preincubated with
      H(2)O(2) showed formation of GLE(-heme)TDWGESWKEARK supporting covalent linkage
      of Glu80 with the heme in the mutant enzyme. No such heme-bound peptides were
      found if the sample was not preincubated in H(2)O(2), indicating no activation of
      the Glu by the heme peroxidase reaction, as proposed earlier. The wild type or
      L80D mutant of the enzyme did not give any heme-bound peptide. Thus, the results
      support the idea that covalent attachment of the heme to an amino acid in the
      protein matrix depends on the structural design of the active site.

PMID- 21192676
TI  - The proapoptotic G41S mutation to human cytochrome c alters the heme electronic
      structure and increases the electron self-exchange rate.
AB  - The naturally occurring G41S mutation to human (Hs) cytochrome (cyt) c enhances
      apoptotic activity based upon previous in vitro and in vivo studies, but the
      molecular mechanism underlying this enhancement remains unknown. Here, X-ray
      crystallography, nuclear magnetic resonance (NMR) spectroscopy, and density
      functional theory (DFT) calculations have been used to identify the structural
      and electronic differences between wild-type (WT) and G41S Hs cyt c. S41 is part
      of the hydrogen bonding network for propionate 7 of heme pyrrole ring A in the X
      ray structure of G41S Hs cyt c and, compared to WT, G41S Hs cyt c has increased
      spin density on pyrrole ring C and a faster electron self-exchange rate. DFT
      calculations illustrate an electronic mechanism where structural changes near
      ring A can result in electronic changes at ring C. Since ring C is part of the
      solvent-exposed protein surface, we propose that this heme electronic structure
      change may ultimately be responsible for the enhanced proapoptotic activity of
      G41S Hs cyt c.

PMID- 21192677
TI  - Dependence of Li2FeSiO4 electrochemistry on structure.
AB  - Small differences in the FeO(4) arrangements (orientation, size, and distortion)
      do influence the equilibrium potential measured during the first oxidation of
      Fe(2+) to Fe(3+) in all polymorphs of Li(2)FeSiO(4).

PMID- 21192678
TI  - Photocontrollable sequence-specific DNA alkylation by a pyrrole-imidazole
      polyamide seco-CBI conjugate.
AB  - We designed and synthesized a Py-Im polyamide seco-CBI conjugate protected by a
      photocleavable group and demonstrated that it was selectively activated by UV
      irradiation both in vitro and in vivo. Sequence-specific alkylating Py-Im
      polyamides containing photolabile linkers may be useful for developing novel
      chemical- or enzyme-activated anticancer agents and may facilitate spatiotemporal
      control of gene expression.

PMID- 21192679
TI  - The use of NH3 to promote the production of large-diameter single-walled carbon
      nanotubes with a narrow (n,m) distribution.
AB  - We demonstrate here a simple and effective (n,m)-selective growth of single
      walled carbon nanotubes (SWCNTs) in an aerosol floating catalyst chemical vapor
      deposition (CVD) process by introducing a certain amount of ammonia (NH(3)).
      Chiralities of carbon nanotubes produced in the presence of 500 ppm NH(3) at 880 
      degrees C are narrowly distributed around the major semiconducting (13,12)
      nanotube with over 90% of SWCNTs having large chiral angles in the range 20
      degrees -30 degrees , and nearly 50% in the range 27 degrees -29 degrees . The
      developed synthesis process enables chiral-selective growth at high temperature
      for structurally stable carbon nanotubes with large diameters.

PMID- 21192680
TI  - Hole injection/transport materials derived from Heck and sol-gel chemistry for
      application in solution-processed organic electronic devices.
AB  - An organosilicate polymer, based on N,N'-diphenyl-N,N'-bis(4-((E)-2
      (triethoxysilyl)vinyl)phenyl)biphenyl-4,4'-diamine (TEVS-TPD) with extended
      conjugation between the Si atom and the aromatic amine, was prepared under mild
      conditions via sequential Heck and sol-gel chemistry and used as an alternative
      to poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS), the most
      widely used planarizing hole injection/transport layer in solution-processed
      organic electronic devices. Spin-coating TEVS-TPD polymer solutions yield defect
      free, uniform, thin films with excellent adhesion to the ITO electrode. Upon
      thermal cross-linking at 180  degrees C, the cross-linked polymer exhibits
      excellent solvent resistance and electrochemical stability. Solution-processed
      organic light emitting diode (OLED) devices using iridium-based triplet emitting
      layers and cross-linked TEVS-TPD films as a hole injection/transport layer show
      significantly improved performance including lower leakage current, lower turn-on
      voltage, higher luminance, and stability at high current density, as compared to
      the control device prepared with PEDOT:PSS.

PMID- 21192682
TI  - Rhodium(I)-catalyzed direct carboxylation of arenes with CO2 via chelation
      assisted C-H bond activation.
AB  - Rh-catalyzed direct carboxylation of unactivated aryl C-H bond under atmospheric
      pressure of carbon dioxide was realized via chelation-assisted C-H activation for
      the first time. Variously substituted and functionalized 2-arylpyridines and 1
      arylpyrazoles underwent the carboxylation in the presence of the rhodium catalyst
      and a stoichiometric methylating reagent, AlMe(2)(OMe), to give carboxylated
      products in good yields. The catalysis is proposed to consist of methylrhodium(I)
      species as the key intermediate, which undergoes C-H activation to afford
      rhodium(III), followed by reductive elimination of methane to give nucleophilic
      arylrhodium(I). This approach demonstrates promising application of C-H bond
      activation strategy in the field of carbon dioxide fixation.

PMID- 21192681
TI  - Molecular simulations of dodecyl-beta-maltoside micelles in water: influence of
      the headgroup conformation and force field parameters.
AB  - This paper deals with the development and validation of new potential parameter
      sets, based on the CHARMM36 and GLYCAM06 force fields, to simulate micelles of
      the two anomeric forms (alpha and beta) of N-dodecyl-beta-maltoside (C(12)G(2)),
      a surfactant widely used in the extraction and purification of membrane proteins.
      In this context, properties such as size, shape, internal structure, and
      hydration of the C(12)G(2) anomer micelles were thoroughly investigated by
      molecular dynamics simulations and the results compared with experiments.
      Additional simulations were also performed with the older CHARMM22 force field
      for carbohydrates (Kuttel, M.; et al. J. Comput. Chem. 2002, 23, 1236-1243). We
      find that our CHARMM and GLYCAM parameter sets yield similar results in the case
      of properties related to the micelle structure but differ for other properties
      such as the headgroup conformation or the micelle hydration. In agreement with
      experiments, our results show that for all model potentials the beta-C(12)G(2)
      micelles have a more pronounced ellipsoidal shape than those containing alpha
      anomers. The computed radius of gyration is 20.2 and 25.4 A for the alpha- and
      beta-anomer micelles, respectively. Finally, we show that depending on the
      potential the water translational diffusion of the interfacial water is 7-11.5
      times slower than that of bulk water due to the entrapment of the water in the
      micelle crevices. This retardation is independent of the headgroup in alpha- or
      beta-anomers.

PMID- 21192683
TI  - PICquant: a quantitative platform to measure differential peptide abundance using
      dual-isotopic labeling with 12C6- and 13C6-phenyl isocyanate.
AB  - We have developed a complete system for the isotopic labeling, fractionation, and
      automated quantification of differentially expressed peptides that significantly
      facilitates candidate biomarker discovery. We describe a new stable mass tagging
      reagent pair, (12)C(6)- and (13)C(6)-phenyl isocyanate (PIC), that offers
      significant advantages over currently available tags. Peptides are labeled
      predominantly at their amino termini and exhibit elution profiles that are
      independent of label isotope. Importantly, PIC-labeled peptides have unique
      neutral-mass losses upon CID fragmentation that enable charge state and label
      isotope identification and, thereby, decouple the sequence identification from
      the quantification of candidate biomarkers. To exploit these properties, we have
      coupled peptide fractionation protocols with a Thermo LTQ-XL LC-MS(2) data
      acquisition strategy and a suite of automated spectrum analysis software that
      identifies quantitative differences between labeled samples. This approach,
      dubbed the PICquant platform, is independent of protein sequence identification
      and excludes unlabeled peptides that otherwise confound biomarker discovery.
      Application of the PICquant platform to a set of complex clinical samples showed
      that the system allows rapid identification of peptides that are differentially
      expressed between control and patient groups.

PMID- 21192684
TI  - Novel ionic iodide-siloxane hybrid electrolyte for dye-sensitized solar cells.
AB  - A novel ionic siloxane hybrid electrolyte was fabricated by thermal
      polymerization of iodide-oligosiloxane resin. The nanosized iodide-oligosiloxane
      was synthesized by a simple sol-gel condensation of 3-iodopropyltrimethoxysilane
      and diphenylsilanediol. It is found that the composition and concentration of the
      oligosiloxane used in the electrolyte affect the performance of the dye
      sensitized solar cells (DSSCs). An optimized DSSC with the hybrid electrolyte
      using smaller molecular-sized oligosiloxane with a greater amount of iodide
      groups presented solar to electricity conversion efficiency of 5.2% at 1 sunlight
      (100 mW cm(-2)), which is comparable to that afforded by a liquid electrolyte.

PMID- 21192685
TI  - Adsorption of gemini surfactants with dodecyl side chains and different spacers,
      including partially fluorinated spacers, on different surfaces: neutron
      reflectometry results.
AB  - Neutron reflectometry has been used to study the adsorption of two symmetrical
      cationic (dimethyl ammonium bromide) gemini surfactants with two C(12)H(25)
      chains and different partially fluorinated spacers at three different surfaces:
      air/water, hydrophilic silica/water, and hydrophobic (octadecyltricholorosilane
      (OTS))/water. In addition, the adsorption of purely hydrocarbon geminis with the
      same side chains and spacers of different lengths has been studied at the same
      two solid surfaces. The limiting close-packed areas for the two fluorocarbon
      geminis, C(12)-C(3)fC(6)C(3)-C(12) and C(12)-C(4)fC(4)C(4)-C(12), are 92 and 72
      +/- 4 at the hydrophilic silica surface, 81 and 89 +/- 4 at OTS, and 137 and 106
      +/- 4 A(2) at the air/water interface with decreases of 38 and 24% from air/water
      to the average solid value, respectively. These changes suggest that the packing
      at the air/water interface is inefficient, and this allows the extra
      hydrophobicity of the chain environment at the two solid surfaces to promote much
      more efficient packing. At the air/water interface, the fluorocarbon spacers are
      on average the fragments furthest away from the underlying water, further out
      than in the nearest comparable hydrocarbon gemini, C(12)-C(12)-C(12). This is the
      probable explanation of the much lower value of the area per molecule at the
      air/water interface of C(12)-C(4)fC(4)C(4)-C(12) compared to that of C(12)-C(12)
      C(12). It is also the probable cause of the inefficient packing of the
      hydrocarbon side chains. At the more hydrophobic OTS surface the situation is
      reversed and the fluorocarbon spacers are now the furthest from the hydrophobic
      surface, further out than the spacer in C(12)-C(12)-C(12). This is an unusually
      large structural change that must be associated with the greatly improved packing
      at the OTS surface. The efficiency of the packing is also high for the
      hydrophilic surface, no doubt because the hydrocarbon chains can interact
      favorably in the adsorbed bilayer core. The values of the area per molecule
      obtained for the series of hydrocarbon geminis at the air/water, OTS/water and
      silica/water interfaces are respectively 139, 104, and 98 +/- 4 A(2) for C(12)
      C(12)-C(12), 114, 106, and 94 +/- 4 A(2) for C(12)-C(10)-C(12), 104, 84, and 85
      +/- 4 A(2) for C(12)-C(6)-C(12), and 78, 66, and 70 +/- 3 A(2) for C(12)-C(3)
      C(12). The area per molecule is also about 20% less on average at the two solid
      surfaces than at the air/water interface. This can also be attributed to more
      efficient packing caused by the more favorable hydrophobic interactions possible
      at these two surfaces than at the air/water interface, again showing that the
      packing at the air/water interface is inefficient and probably resulting from the
      competition between spacer and chains, which will be most pronounced for the
      C(12) spacer.

PMID- 21192686
TI  - Local velocity measurements in the shear-thickening transition of dilute micellar
      solutions of surfactants.
AB  - Local velocimetry and rheometric measurements are performed on three dilute
      micellar solutions which undergo the shear-thickening transition. The three
      surfactants, namely, alkyltrimethyl ammonium bromide (C(n)TAB), all belong to the
      same family and only differ by the length of the aliphatic chain. Simultaneous
      ultrasonic velocimetry and rheometry recordings provide convincing evidence for a
      heterogeneous flow in the shear-thickening domain. A detailed analysis allows us
      to demonstrate surprisingly similar evolutions of the wall slip magnitude and of
      the apparent viscosity as well as subtle differences between the three systems.
      Together with the velocimetry results, the direct observation of the flow in the
      vorticity-velocity plane reveals that the shear-thickening transition is
      associated with the emergence of a three-dimensional unstable flow.

PMID- 21192687
TI  - Phase-selective chemical extraction of selenium and sulfur from nanoscale metal
      chalcogenides: a general strategy for synthesis, purification, and phase
      targeting.
AB  - Controlling the composition and phase formation of bulk and nanoscale solids
      underpins efforts to control physical properties. Here, we introduce a powerful
      new chemical pathway that facilitates composition-tunable synthesis, post
      synthesis purification, and precise phase targeting in metal chalcogenide
      systems. When metal selenides and sulfides react with trioctylphosphine (TOP) at
      temperatures that range from 65 to 270  degrees C, selenium and sulfur are
      selectively extracted to produce the most metal-rich chalcogenide that is stable
      in a particular binary system. This general approach is demonstrated for SnSe(2),
      FeS(2), NiSe(2), and CoSe(2), which convert to SnSe, FeS, Ni(3)Se(2), and
      Co(9)Se(8), respectively. In-depth studies of the Fe-Se system highlight the
      precise phase targeting and purification that is achievable, with PbO-type FeSe
      (the most metal-rich stable Fe-Se phase) forming exclusively when other Fe-Se
      phases, including mixtures, react with TOP. This chemistry also represents a new
      template-based nanoparticle "conversion chemistry" reaction, transforming hollow
      NiSe(2) nanospheres into hollow NiSe nanospheres with morphological retention.

PMID- 21192689
TI  - Phase behavior and rheological properties of salt-free catanionic TTAOH/DA/H2O
      system in the presence of hydrophilic and hydrophobic salts.
AB  - In the cationic and anionic (catanionic) surfactant mixed system,
      tetradecyltrimethylammonium hydroxide (TTAOH)/decanoic acid (DA)/H(2)O, abundant
      phase behaviors were obtained in the presence of hydrophilic and hydrophobic
      salts. The microstructures of typical L(alpha) phases with the different
      compositions were characterized by the transmission electron microscope (TEM)
      images. Aqueous double-phase transition induced by addition of hydrophilic salts
      was observed when the cationic surfactant was in excess. Salt-induced reversible
      vesicle phases could be obtained when the anionic surfactant was excess, whereas
      the vesicle phase at lower salinity behaves highly viscoelastic but is much less
      viscoelastic with high salinity which was demonstrated by measuring their
      rheological properties. The L(alpha) phase with the positive membrane charges can
      be finally transferred into an L(1) phase with added salts. The ion specificity
      of hydrophilic and hydrophobic salts is discussed, and the order of cations is
      summarized, which is significant for the further study of the Hofmeister effects
      on catanionic surfactant mixed systems.

PMID- 21192688
TI  - Lipid metabolism and peroxisome proliferator-activated receptor signaling
      pathways participate in late-phase liver regeneration.
AB  - Liver regeneration (LR) is of great clinical significance in various liver
      associated diseases. LR proceeds along a sequence of three distinct phases:
      priming/initiation, proliferation, and termination. Compared with the recognition
      of the first two phases, little is known about LR termination and
      structure/function reorganization. A combination of "omics" techniques, along
      with bioinformatics, may provide new insights into the molecular mechanism of the
      late-phase LR. Gene, protein, and metabolite profiles of the rat liver were
      determined by cDNA microarray, two-dimensional electrophoresis, and HPLC-MS
      analysis. Pathway enrichment analysis was performed to identify the pathways: 427
      differentially expressed genes extracted from the microarray experiment revealed
      two expression patterns representing the early and late phase of LR.
      Functionally, the genes expressing at a higher level at the early phase than at
      the late phase were mainly involved in the response to stress, proliferation, and
      resistance to apoptosis, while those expressing at a lower level at the early
      phase than at the late phase were mainly engaged in lipid metabolism. Compared
      with the sham-operation control (SH) group, 5 proteins in the 70% partial
      hepatectomy (70%PHx) group were upregulated at the protein level, and 3 proteins
      were downregulated at 168 h after the 70%PHx. E-FABP, an upregulated fatty acid
      binding protein, was found to be involved in the peroxisome proliferator
      activated receptor (PPAR) signaling pathway. The metabolomic data confirmed the
      enhancement of lipid metabolism by the detection of the intermediate and final
      metabolites. We've concluded that increased lipid metabolism and activated PPAR
      signaling pathways play important roles in late-phase LR.

PMID- 21192690
TI  - Evaluation of asphaltene degradation on highly ordered TiO2 nanotubular arrays
      via variations in wettability.
AB  - Photocatalytic degradation of both aquatic and atmospheric organic pollutants on
      titanium dioxide has been extensively investigated in the past decades, but
      research on direct photocatalytic degradation of solid-phase organic pollutants
      is rather limited. In this work, photocatalytic degradation of n-C(7) asphaltene,
      which is composed of solid-phase organic substances found in crude oil, on highly
      ordered TiO(2) nanotubular arrays (TNAs) was studied using the wettability as an
      indicator. It was observed that the water contact angle rose linearly with
      increasing the concentration of n-C(7) asphaltene solution up to 0.02 g mL(-1).
      Further increasing the concentration of n-C(7) asphaltene only caused small
      augment in the contact angle, which eventually became stable around 98 degrees .
      It is demonstrated that the water contact angle can be used as an indicator to
      reflect the residual solid-phase organic pollutants within a certain range of
      pollutant concentration. As observed, n-C(7) asphaltene film degraded on TNAs
      under UV illumination for 60 min, showing complete mineralization of ~80% of n
      C(7) asphaltene that was released into air finally. The remaining 20% of
      asphaltene was partially decomposed into smaller organic molecules, e.g., -C(?O)-
      and -C(?O)-OH, confirmed by high-resolution X-ray photoelectron spectra analysis.
      TNAs can be reused to degrade the solid-phase n-C(7) asphaltene for a number of
      cycles without further treatment.

PMID- 21192691
TI  - Nanoporous PdNi Alloy Nanowires As Highly Active Catalysts for the Electro
      Oxidation of Formic Acid.
AB  - Highly active and durable catalysts for formic acid oxidation are crucial to the
      development of direct formic acid fuel cell. In this letter, we report the
      synthesis, characterization, and electrochemical testing of nanoporous
      Pd(57)Ni(43) alloy nanowires for use as the electrocatalyst towards formic acid
      oxidation (FAO). These nanowires are prepared by chemically dealloying of Ni from
      Ni-rich PdNi alloy nanowires, and have high surface area. X-ray diffraction data
      show that the Pd(57)Ni(43) nanowires have the face-centered cubic crystalline
      structure of pure Pd, whereas X-ray photoelectron spectroscopy confirm the
      modification of electronic structure of Pd by electron transfer from Ni to Pd.
      Electrocatalytic activity of the nanowires towards FAO exceeds that of the state
      of-the-art Pd/C. More importantly, the nanowires are highly resistant to
      deactivation. It is proposed that the high active surface area and modulated
      surface properties by Ni are responsible for the improvement of activity and
      durability. Dealloyed nanoporous Pd(57)Ni(43) alloy nanowires are thus proposed
      as a promising catalyst towards FAO.

PMID- 21192693
TI  - Hierarchical porous materials made by drying complex suspensions.
AB  - Porous structures containing pores at different length scales are often
      encountered in nature and are important in many applications. While several
      processing routes have been demonstrated to create such hierarchical porous
      materials, most methods either require chemical gelation reactions or do not
      allow for the desired control of pore sizes over multiple length scales. We
      describe a versatile and simple approach to produce tailor-made hierarchical
      porous materials that relies solely on the process of drying. Our results show
      that simple drying of a complex suspension can lead to the self-assembly of
      droplets, colloidal particles and molecular species into unique 3D hierarchical
      porous structures. Using a microfluidic device to produce monodisperse templating
      droplets of tunable size, we prepared materials with up to three levels of
      hierarchy exhibiting monodisperse pores ranging from 10 nm to 800 MUm. While the
      size of macropores obtained after drying is determined by the size of initial
      droplets, the interconnectivity between macropores is strongly affected by the
      type of droplet stabilizer (surfactants or particles). This simple route can be
      used to prepare porous materials of many chemical compositions and has great
      potential for creating artificial porous structures that capture some of the
      exquisite hierarchical features of porous biological materials.

PMID- 21192692
TI  - Distinct ligand specificity of the Tiam1 and Tiam2 PDZ domains.
AB  - Guanine nucleotide exchange factor proteins of the Tiam family are activators of
      the Rho GTPase Rac1 and critical for cell morphology, adhesion, migration, and
      polarity. These proteins are modular and contain a variety of interaction
      domains, including a single post-synaptic density-95/discs large/zonula occludens
      1 (PDZ) domain. Previous studies suggest that the specificities of the Tiam1 and
      Tiam2 PDZ domains are distinct. Here, we sought to conclusively define these
      specificities and determine their molecular origin. Using a combinatorial peptide
      library, we identified a consensus binding sequence for each PDZ domain. Analysis
      of these consensus sequences and binding assays with peptides derived from native
      proteins indicated that these two PDZ domains have overlapping but distinct
      specificities. We also identified residues in two regions (S(0) and S(-2)
      pockets) of the Tiam1 PDZ domain that are important determinants of ligand
      specificity. Site-directed mutagenesis of four nonconserved residues in these two
      regions along with peptide binding analyses confirmed that these residues are
      crucial for ligand affinity and specificity. Furthermore, double mutant cycle
      analysis of each region revealed energetic couplings that were dependent on the
      ligand being investigated. Remarkably, a Tiam1 PDZ domain quadruple mutant had
      the same specificity as the Tiam2 PDZ domain. Finally, analysis of Tiam family
      PDZ domain sequences indicated that the PDZ domains segregate into four distinct
      families based on the residues studied here. Collectively, our data suggest that
      Tiam family proteins have highly evolved PDZ domain-ligand interfaces with
      distinct specificities and that they have disparate PDZ domain-dependent
      biological functions.

PMID- 21192694
TI  - PS colloidal particles stabilized by graphene oxide.
AB  - Exfoliated graphene oxide (GO) sheets with hydrophilic functional groups on the
      surface were prepared by the oxidation of graphite. Because of the hydrophilic
      groups on the sheets and the hydrophobic carbon surface, GO sheets were located
      at the oil-water interface and could be used as a stabilizer in Pickering
      emulsions. After the Pickering emulsion polymerization of styrene, PS colloidal
      particles with GO sheets on the surface were prepared. The size of the GO sheets
      exerts an important influence on the preparation of PS colloidal particles. Small
      GO sheets located at the liquid-liquid interface and GO-stabilized PS colloidal
      particles were prepared; however, for large GO sheets, smaller PS colloidal
      particles prepared on the GO surface were observed. Transmission electron
      microscopy (TEM), scanning electron microscopy (SEM), and X-ray photoelectron
      spectroscopy (XPS) were used to characterize the structure and morphology of the
      colloidal particles. TEM, SEM, and XPS results all suggest the successful
      preparation of GO-stabilized PS colloidal particles.

PMID- 21192695
TI  - Characterizing protein activities on the lysozyme and nanodiamond complex
      prepared for bio applications.
AB  - Recently, nanodiamond particles have attracted increasing attention as a
      promising nanomaterial for its biocompatibility, easy functionalization and
      conjugation with biomolecules, and its superb physical/chemical properties.
      Nanodiamonds are mainly used as markers for cell imaging, using its fluorescence
      or Raman signals for detection, and as carriers for drug delivery. For the
      success of these applications, the biomolecule associated with the nanodiamond
      has to retain its functionality. In this work, the protein activities of egg
      white lysozyme adsorbed on nanodiamond particles of different sizes is
      investigated. The lysozyme nanodiamond complex is used here as a protein model
      for analyzing its structural conformation changes and, correspondingly, its
      enzymatic activity after the adsorption. Fourier-transform infrared spectroscopy
      (FTIR) is used for the analysis of the sensitive protein secondary structure. To
      access the activities of the adsorbed lysozyme, a fluorescence-based assay is
      used. The process of adsorption is also analyzed using UV-visible spectroscopic
      measurements in combination with analysis of nanodiamond properties with FTIR,
      Raman spectroscopy, and zeta-potential measurements. It is found that the
      activity of lysozyme upon adsorption depends on the nanodiamond's size and
      surface properties, and that the nanodiamond particles can be selected and
      treated, which do not alter the lysozyme functional properties. Such nanodiamonds
      can be considered convenient nanoparticles for various bioapplications.

PMID- 21192696
TI  - Lipidomics profiling by high-resolution LC-MS and high-energy collisional
      dissociation fragmentation: focus on characterization of mitochondrial
      cardiolipins and monolysocardiolipins.
AB  - A liquid chromatography-mass spectrometry (LC-MS) method was used for separation
      of lipid classes as well as both qualitative and semiquantitative detection of
      individual lipids in biological samples. Data were acquired using high-resolution
      full-scan MS and high-energy collisional dissociation (HCD) all ion
      fragmentation. The method was evaluated for efficient separation and detection in
      both positive and negative ionization mode using standards spanning six lipid
      classes. Platform linearity and robustness, related to the mitochondrial lipid
      cardiolipin (CL), were assessed using extracted ion chromatograms with mass
      tolerance windows of 5 ppm or less from full scan exact mass measurements. The
      platform CL limit of detection was determined to be 5 pmol (0.9 MUM) on the
      column, with mass accuracy <1.5 ppm, retention time coefficients of variation
      (CV) < 0.5%, and area CV < 13%. This mass accuracy was critical to the
      identification of unknown CL species in mitochondria samples, through the
      elimination of false positives. In addition to detection and relative
      quantitation of CL species in mitochondria, CL structures were characterized
      through the use of alternating HCD scans at different energies to produce
      diagnostic fragmentations on all ions in the analysis. The developed lipid
      profiling method was applied to mitochondrial samples from an animal study
      related to the linkages between diet, mitochondrial function, and disease. The
      analysis identified 28 unique CL species and two monolysocardiolipin species that
      are often associated with mitochondrial stress and dysfunction.

PMID- 21192697
TI  - Equilibrium geometries, stabilities, and electronic properties of the bimetallic
      M2-doped Au(n) (M = Ag, Cu; n = 1-10) clusters: comparison with pure gold
      clusters.
AB  - The density functional method with relativistic effective core potential has been
      employed to investigate systematically the geometrical structures, relative
      stabilities, growth-pattern behaviors, and electronic properties of small
      bimetallic M(2)Au(n) (M = Ag, Cu; n = 1-10) and pure gold Au(n) (n <= 12)
      clusters. The optimized geometries reveal that M(2) substituted Au(n+2) clusters
      and one Au atom capped M(2)Au(n-1) structures are dominant growth patterns of the
      stable alloyed M(2)Au(n) clusters. The calculated averaged atomic binding
      energies, fragmentation energies, and the second-order difference of energies as
      a function of the cluster size exhibit a pronounced even-odd alternation
      phenomenon. The analytic results exhibit that the planar structure Ag(2)Au(4) and
      Cu(2)Au(2) isomers are the most stable geometries of Ag(2)Au(n) and Cu(2)Au(n)
      clusters, respectively. In addition, the HOMO-LUMO gaps, charge transfers,
      chemical hardnesses and polarizabilities have been analyzed and compared further.

PMID- 21192698
TI  - Interactions of Abeta25-35 beta-barrel-like oligomers with anionic lipid bilayer
      and resulting membrane leakage: an all-atom molecular dynamics study.
AB  - Abeta25-35, a proteolytic fragment of the Alzheimer amyloid beta (Abeta) peptide,
      is produced in the brains of Alzheimer's patients and retains the neurotoxicity
      of its full-length counterpart. The formation of pores/channels in membranes has
      been reported as one of the mechanisms responsible for Abeta25-35 toxicity. In
      addition, it has been proposed that pore/channel might be formed by the
      aggregation of Abeta25-35 in membranes into a beta-barrel structure. However, the
      structure of the beta-barrel and its perturbation on the ordering of lipid
      bilayer at atomic level remain elusive. In this study, we have investigated the
      interactions of three types of preformed Abeta25-35 beta-barrels (labeled as
      barrels A, B, and C) with negatively charged palmitoyloleoylphosphatidylglycerol
      (POPG) lipid bilayers using all-atom molecular dynamics (MD) simulations. Each
      type of Abeta25-35 beta-barrel consists of eight beta-strands with positively
      charged side chains of lysine residues oriented toward the interior or exterior
      of the barrel. Barrels A, B, and C have respectively an out-of-register mixed
      parallel-antiparallel (taken from our previous study), in-register mixed parallel
      antiparallel, and in-register antiparallel beta-strand arrangements. Simulations
      have been performed by employing the initial configurations where the beta
      barrels are fully or partially inserted into the bilayer. On the basis of nine
      independent 150 ns MD runs for the full-insertion system, we found that barrels A
      and C slightly affect the local ordering of lipid bilayer, while barrel B
      perturbs the local structure of membrane and even causes membrane leakage for
      water by forming nanometer-sized hydrophilic pore when lysine residues on its
      inner side. Two 100 ns MD simulations on partial-insertion system show that
      partial insertion of Abeta25-35 beta-barrel in the bilayer results in a tendency
      to stay inside for barrel B. These results suggest that barrel B with Lys
      residues on its inner side is the most likely Abeta25-35 pore structure leading
      to membrane leakage. Our MD simulations provide significant insight into the
      atomic resolution structure of Abeta25-35 beta-sheet-rich pores and the membrane
      disruption mechanism induced by Abeta25-35 amyloid pores.

PMID- 21192699
TI  - Synthesis of 2',3'-dideoxynucleoside phosphoesters using H-phosphonate chemistry
      on soluble polymer support.
AB  - Phosphorylation of ddC and 3TC was efficiently performed on soluble poly(ethylene
      glycol) support. The corresponding 5'-monophosphate derivatives were obtained by
      oxidation of the support bound 5'-H-phosphonate intermediates. Then, di- and
      triphosphorylations were carried out using a carbonyldiimidazole activation step
      followed by nucleophilic substitution with suitable phosphate salts. Trivalent
      phosphorus chemistry appeared as a good alternative for monophosphate synthesis
      of acid-sensitive 2',3'-dideoxynucleosides.

PMID- 21192700
TI  - Coarse-grained molecular dynamics simulations of cobra cytotoxin A3 interactions
      with a lipid bilayer: penetration of loops into membranes.
AB  - Cobra cytotoxins, which are small three-looped proteins composed of approximately
      60 amino acid residues, primarily act by destroying the bilayer membranes of
      cells and artificial vesicles. However, the molecular mechanism governing this
      process is not yet completely understood. We used coarse-grained molecular
      dynamics (CGMD) simulations to study the mechanism underlying the penetration of
      cardiotoxin A3 (CTX A3), the major toxic component of Naja atra (Chinese cobra)
      venom, into a hydrated 1-palmitoyl-2-oleoyl-1-sn-3-phosphatidylcholine (POPC)
      lipid bilayer. We performed CGMD simulations for three different conformations of
      the cobra cytotoxin-the tail, lying, and harrow conformations. The results of our
      simulations indicate that two of these, the tail and lying conformations, did not
      penetrate the bilayer system. Further, for the harrow conformation, loops 2 and 3
      played important roles in penetration of CTX A3 into the bilayer system.

PMID- 21192701
TI  - Self-assembly of CdTe nanoparticles into dendrite structure: a microsensor to
      Hg2+.
AB  - A novel microsensor to Hg(2+) was fabricated through self-assembly of aqueous
      CdTe nanoparticles (NPs). The morphologies of self-assembly mainly included
      classical dendrites, straight dendrites, and small islands. The formation process
      of these morphologies was systematically investigated by using the field emission
      scanning electron microscope, confocal laser scanning microscope, and atom force
      microscope instruments, etc. The proposed mechanism showed that the dendrite
      structure was formed via manipulating the short-range van der Waals interaction
      and long-range electrostatic interaction, which was realized through altering the
      ligand and concentration of the CdTe NPs. Furthermore, polymers with positive
      charges were used to effectively control the morphology of the self-assembly as
      well as improve the property of photoluminescence. These CdTe dendrites were used
      as microsensors to Hg(2+), which presented the advantages of low cost, quick
      detection time, high selectivity, and easy operation.

PMID- 21192702
TI  - Consumption of oxidized oil increases oxidative stress in broilers and affects
      the quality of breast meat.
AB  - A total of 120 4-week-old broiler chickens were allotted to 12 pens and fed one
      of three diets including control, oxidized diet (5% oxidized oil), or antioxidant
      added diet (500 IU vitamin E) for 2 weeks. Blood samples were collected at the
      end of feeding trial, and breast muscles were sampled immediately after
      slaughter. Breast meats were also collected 24 h after slaughter and used for
      meat quality measurements. Oxidative stress in blood, lipid and protein
      oxidation, and sarcoplasmic reticulum Ca2(+)-ATPase (SERCA) activity of breast
      muscle were determined. The oxidized diet increased oxidative stress in blood and
      increased carbonyl content in breast meat compared with the other two dietary
      treatments (P < 0.05). Lipid oxidation of breast muscles with the antioxidant
      supplemented diet was lower than that with the oxidized and control diet groups
      (P < 0.05). Meat from birds fed the oxidized diet showed higher drip loss after 1
      and 3 days of storage and greater 0-1 h post-mortem pH decline (P < 0.05).
      Significant differences in specific SERCA activity in breast muscles from birds
      fed control and oxidized diets (P < 0.05) were detected. This suggested that
      dietary oxidized oil induced oxidative stress in live birds and increased lipid
      and protein oxidation in breast muscle. Decrease in SERCA activity in breast
      muscles due to oxidative stress in live animals accelerated post-mortem
      glycolysis, which sped the pH drop after slaughter and increased drip loss,
      indicating that oxidation of diet can cause PSE-like (pale, soft, and exudative)
      conditions in broiler breast muscles.

PMID- 21192703
TI  - Production of conjugated linoleic acid (CLA) by Bifidobacterium breve LMC520 and
      its compatibility with CLA-producing rumen bacteria.
AB  - This study was performed to characterize the ability of an active Bifidobacterium
      strain to produce conjugated linoleic acid (CLA) and to test its possible
      utilization as a probiotic compatible to the ruminal condition. Bifidobacterium
      breve LMC520 can actively convert linoleic acid (LA) to cis-9,trans-11-CLA, which
      is a major isomer derived from microbial conversion. LMC520 showed reasonable
      tolerance under acidic conditions (pH 2.5 with 1% pepsin) and in the presence of
      oxgall (0-3%). The growth and CLA production of LMC520 were tested under ruminal
      conditions and compared with those of Butyrivibrio fibrisolvens A38, which is a
      major CLA producer in the rumen as an intermediate in the biohydrogenation (BH)
      process. LMC520 converted 15% of LA to CLA under ruminal conditions, which was 2
      times higher activity than that of A38, and there was no decline in CLA level
      during prolonged incubation of 48 h. The BH activity of LMC520 was comparable to
      that of A38. When LMC520 was cocultured with A38, even with slight decrease of
      CLA due to high BH activity by A38, but the level of CLA was maintained by the
      high CLA-producing activity of LMC520. This comparative study shows the potential
      of this strain to be applied as a functional probiotic not only for humans but
      also for ruminants as well as to increase CLA production.

PMID- 21192704
TI  - Enantiomeric discrimination and quantification of the chiral organophosphorus
      pesticide fenamiphos in aqueous samples by a novel and selective 31P nuclear
      magnetic resonance spectroscopic method using cyclodextrins as chiral selector.
AB  - A rapid, selective, and accurate quantitative 31P nuclear magnetic resonance (31P
      NMR) spectroscopy method was used for the chiral recognition of the racemic
      organophosphorus pesticide fenamiphos using chiral solvating agents (CSAs). Six
      neutral cyclodextrins (CDs) (alpha-CD, beta-CD, methyl-beta-CD, hydroxyethyl-beta
      CD, hydroxypropyl-beta-CD, and hydroxypropyl-gamma-CD) and two anionic CDs
      (carboxymethyl-beta-CD and carboxyethyl-beta-CD) were selected for these
      experiments. The shift displacement values (Deltadelta), after addition of each
      of the eight CDs in the highest possible molar ratio to a guest, were recorded.
      The results showed that beta-CD and hydroxypropyl-beta-CD were the best chiral
      solvating agents for the enantiomeric discrimination of fenamiphos. Two-dimension
      rotating frame nuclear Overhauser spectroscopy (ROESY) was used to investigate
      the structure of the beta-CD-fenamiphos inclusion complex in aqueous solution. To
      determine the fenamiphos enantiomers, a calibration curve was drawn for two
      enantiomers over the range of 0.05-0.25 mg mL-1. The limits of detection (S/N =
      3) were obtained as 0.0068 and 0.0060 mg mL-1 for fenamiphos enantiomers. The
      recovery studies were performed on aqueous real samples ranging from 94 to 107%
      with coefficients of variation of <= 9%.

PMID- 21192705
TI  - In situ observation and measurement of evaporation-induced self-assembly under
      controlled pressure and temperature.
AB  - In situ observations of evaporation-induced colloidal self-assembly and in situ
      measurement of mass transfer process were carried out under a temperature and
      pressure controlling system. The growth processes of colloidal crystals in
      different cuvettes recorded by direct video observations revealed that solvent
      flow around the pore space of the crystal played a key role. By changing the
      circumstances (temperature and pressure) of the self-assembly system and
      properties of fluid (viscosity), different evaporation rate of solvent and growth
      rate of colloidal crystals were measured directly. It turned out that both
      evaporation rate and growth rate as functions of temperature and pressure fit
      Stefan's law well. Furthermore, the transfer process of particles in the fluid
      flow was determined by the fluid-dynamic characteristics, which can be analyzed
      by the Reynolds number. The results obtained provide an insight into the growth
      mechanisms of self-assembly and theoretical basis for optimizing the experimental
      growth conditions of colloidal crystals.

PMID- 21192706
TI  - Technetium(I) carbonyl dithiocarbamates and xanthates.
AB  - Technetium(I) tetracarbonyl complexes with diethyldithiocarbamate and
      methylxanthate ligands [TcL(CO)(4)] (L = S(2)CNEt(2) and S(2)COMe) were prepared.
      Conditions required for the formation of these complexes were found. The crystal
      and molecular structure of the xanthate complex was determined by single-crystal
      X-ray diffraction. [Tc(S(2)CNEt(2))(CO)(4)] undergoes decarbonylation both in
      solution and in the course of vacuum sublimation with the formation of a dimer
      [Tc(S(2)CNEt(2))(CO)(3)](2) whose structure was determined by single-crystal X
      ray diffraction. In donor solvents, [Tc(S(2)CNEt(2))(CO)(4)] and
      [Tc(S(2)COMe)(CO)(4)] undergo decarbonylation with the formation of tricarbonyl
      solvates [TcL(CO)(3)(Sol)]. The crystal structure of the pyridine solvate
      [Tc(S(2)CNEt(2))(CO)(3)(py)], chosen as an example, was determined by single
      crystal X-ray diffraction. The possibility of using bidentate S-donor acidic
      ligands for tethering the tetracarbonyltechnetium fragment to biomolecules was
      examined.

PMID- 21192707
TI  - Shedding light into the detailed excited-state relaxation pathways and reaction
      mechanisms of thionaphthol isomers.
AB  - Nanosecond laser flash photolysis employing transient detection of emission and
      absorption in combination with pulse radiolysis and quantum theory has been
      employed to shed light into the kinetics, quantum yields, and mechanisms of the
      deactivation of the first excited singlet state of 1- and 2-thionaphthols
      (NpSH(S(1))). In contrast to thiophenols (ArSH(S(1))), the results revealed that
      the decay of the first excited singlet state of 1- and 2-thionaphthols
      (NpSH(S(1))) is governed by radiationless internal conversion (Phi(IC) = 0.29
      0.46; 0.016-0.190) and intersystem crossing (Phi(ISC) = 0.14-0.15; 0.4-0.6),
      respectively, with pronounced S-H photodissociation (Phi(D) = 0.40-0.55; 0.35
      0.40). Fluorescence as a deactivation channel plays a minor role (Phi(F) = 0.001
      0.010; 0.010-0.034). Quantum chemical calculations helped in understanding the
      formation of naphthylthiyl radicals and rationalizing the differences in the
      efficiency of intersystem crossing of the 1- and 2-thionaphthol systems.

PMID- 21192708
TI  - Evaluation of surface plasmon resonance biosensors for detection of tetrodotoxin
      in food matrices and comparison to analytical methods.
AB  - Tetrodotoxin (TTX) is a low molecular weight neurotoxin found in a number of
      animal species, including pufferfish. One emerging method for TTX detection
      employs surface plasmon resonance (SPR) immunosensors. SPR, an optical technique
      that allows for label-free, real-time, multiplexed analysis, can have detection
      limits that rival many of the conventional transduction methods. Preliminary SPR
      approaches for TTX were successful, yet suffered from low throughput and used
      noncommercial instrumentation. To advance this method for broader use, the
      immunoassay was transferred to a commercial instrument and optimized for improved
      detection. This manuscript outlines the assay development and results for complex
      matrices relevant to seafood safety (pufferfish) and food adulteration (milk,
      apple juice). In addition, results are compared to those obtained using receptor
      binding assay, ELISA, HPLC-FD, and LC/MS/MS detection techniques. Results
      highlight the advantages of SPR assays, including rapid screening capability with
      low reagent consumption and low- to subppb detection limits.

PMID- 21192709
TI  - Dendritic poly(ether imine) based gene delivery vector.
AB  - The nonviral vector based gene delivery approach is attractive due to advantages
      associated with molecular-level modifications suitable for optimization of vector
      properties. In a new class of nonviral gene delivery systems, we herein report
      the potential of poly(ether imine) (PETIM) dendrimers to mediate an effective
      gene delivery function. PETIM dendrimer, constituted with tertiary amine branch
      points, n-propyl ether linkers and primary amines at their peripheries, exhibits
      significantly reduced toxicities, over a broad concentration range. The dendrimer
      complexes pDNA effectively, protects DNA from endosomal damages, and delivers to
      the cell nucleus. Gene transfection studies, utilizing a reporter plasmid pEGFP
      C1 and upon complexation with dendrimer, showed a robust expression of the
      encoded protein. The study shows that PETIM dendrimers are hitherto unknown novel
      gene delivery vectors, combining features of poly(ethylene imine)-based polymers
      and dendrimers, yet are relatively nontoxic and structurally precise.

PMID- 21192710
TI  - Exploring the intermediate states of ADP-ATP exchange: a simulation study on Eg5.
AB  - While mitotic kinesins have attracted significant attention in recent years as
      new anticancer drug targets, the underlying mechanism of kinesin-catalyzed ATP
      hydrolysis is still under investigation. Crystal structures of Eg5, one of the
      best-studied kinesins, have been solved in both ADP-bound and ATP-bound states.
      However, it is still extremely challenging to experimentally obtain structural
      information on the functionally important intermediate states, such as the
      nucleotide free (apo) and the initial ATP-kinesin collision state. Systematic
      molecular dynamics simulations were performed in this study to mimic different
      nucleotide binding states and explore the critical structural and dynamic
      variations during ADP-ATP exchange. Clear conformational changes from "ADP-like"
      toward "ATP-like" were observed from the simulation results. A highly conserved
      residue Arg(234) was found to play a key role during the nucleotide exchange.
      This positively charged residue acted as the "hub" of a hydrogen-bond network
      that extended the effect of gamma-phosphoryl group to both SW-I and SW-II
      regions. Comparison among the results of different nucleotide binding states
      indicated that the existence of gamma-phosphoryl was immediately sensed at the
      initial ATP collision state by residue Ser(233), and this initial interaction
      induced the "back-door" opening and the "front-door" closing of the nucleotide
      binding pocket. In addition, several potential allosteric binding sites were
      identified through combination of correlation analysis and binding site mapping
      approaches based on the simulated apo ensemble, which provided additional
      targeting sites for novel allosteric Eg5 inhibition. These molecular simulation
      results provided not only a better understanding of Eg5-catalyzed ATP hydrolysis
      but also the structural basis for design of novel specific Eg5 inhibitors as
      anticancer therapeutic agents.

PMID- 21192711
TI  - Unusually large magnetic anisotropy in a CuO-based semiconductor Cu5V2O10.
AB  - A CuO-based material Cu(5)V(2)O(10) was successfully grown in a closed crucible
      using Sr(OH)(2).8H(2)O as flux. The structure of Cu(5)V(2)O(10) can be viewed as
      being composed of two types of zigzag Cu-O chains running along the b- and c
      axes, which shows a two-dimensional crosslike framework with 12-column square
      tunnels along the a-axis. Magnetic measurements show that Cu(5)V(2)O(10) exhibits
      unexpected large magnetic anisotropy, which is the first time magnetic anisotropy
      energy of ~10(7) erg/cm(3) in the CuO-based materials has been observed. The
      origins of large anisotropy are suggested to arise from strong anisotropic
      exchanges due to the particular bonding geometry and the Jahn-Teller distortion
      of Cu(2+) ions. Further, the band structure investigated by the GGA+U method
      suggests that Cu(5)V(2)O(10) is a semiconductor.

PMID- 21192712
TI  - Fabrication and evaluation of ZnO nanorods by liquid-phase deposition.
AB  - The ZnO nanorod growth mechanism during liquid-phase deposition (LPD) has been
      investigated, with results considered in the context of phase stabilization, LPD
      chemical processes, and Gibbs free energy and entropy. Zinc oxide (ZnO) possesses
      unique optical and electronic properties, and obtaining ZnO species with high
      specific surface area is important in ZnO applications. Highly c-axis-oriented
      ZnO films are expected to be utilized in future optical and electrical devices.
      ZnO nanorods were synthesized using an aqueous solution deposition technique on a
      glass substrate with a free-standing ZnO nanoparticle layer. ZnO nanorod growth
      was easily controlled on the nanoscale by adjustment of the immersion time (15
      210 min). X-ray diffraction, field-emission scanning electron microscopy (FE
      SEM), and film thickness measurements were used to characterize the crystalline
      phase, orientation, morphology, microstructure, and growth mechanism of the ZnO
      nanorods. FE-SEM images were analyzed by image processing software, which
      revealed details of the of ZnO nanorod growth mechanism.

PMID- 21192713
TI  - Functionally strain-graded nanoscoops for high power Li-ion battery anodes.
AB  - Lithium-ion batteries show poor performance for high power applications involving
      ultrafast charging/discharging rates. Here we report a functionally strain-graded
      carbon-aluminum-silicon anode architecture that overcomes this drawback. It
      consists of an array of nanostructures each comprising an amorphous carbon
      nanorod with an intermediate layer of aluminum that is finally capped by a
      silicon nanoscoop on the very top. The gradation in strain arises from graded
      levels of volumetric expansion in these three materials on alloying with lithium.
      The introduction of aluminum as an intermediate layer enables the gradual
      transition of strain from carbon to silicon, thereby minimizing the mismatch at
      interfaces between differentially strained materials and enabling stable
      operation of the electrode under high-rate charge/discharge conditions. At an
      accelerated current density of ~51.2 A/g (i.e., charge/discharge rate of ~40C),
      the strain-graded carbon-aluminum-silicon nanoscoop anode provides average
      capacities of ~412 mAh/g with a power output of ~100 kW/kg(electrode)
      continuously over 100 charge/discharge cycles.

PMID- 21192714
TI  - Cyano-bridged pentanuclear and honeycomblike M(III)Cu(II) (M = Fe, Cr) bimetallic
      assemblies: structural variations modulated by side groups of macrocyclic ligands
      and magnetic properties.
AB  - Three two-dimensional (2D) layered M(III)-Cu(II) (M = Fe, Cr) bimetallic
      complexes and a discrete cluster were prepared using [M(CN)(6)](3-) and
      respective Cu macrocycles with methyl (1, 3) or ethyl (2, 4) side groups. The
      crystal structures can be described as aesthetic honeycomb-like M(2)Cu(3) neutral
      sheets (1, 3, 4) and a pentanuclear Fe(2)Cu(3) entity (2) with an isolated
      Cu(L2)(2+) moiety. The steric hindrance induced by the pendant groups renders the
      internal parameters of the Cu-N(ax) (where the "ax" subscript denotes axial)
      length and Cu-N(ax)-C(ax) angle to become elongated and acute. The magnetic data
      disclose that ferromagnetic couplings are transmitted between M(III) and Cu(II)
      ions through the CN links. For 4, particularly, there is a magnetically defined
      chain (J(c)) composed of dimers (J(d)) and trimers (J(t)), based on the
      structural considerations. The intramolecular magnetic coupling constants are
      J(d) = 3.73 cm(-1) and J(t) = 4.08 cm(-1), while the J(c) value corresponds to
      0.17 cm(-1). From a magnetostructural point of view, it is reasoned that the Cu
      N(ax) bond length is probably a determining factor of the strength of magnetic
      couplings in 4.

PMID- 21192715
TI  - Steroids with aromatic A-rings from the Hainan soft coral Dendronephthya studeri
      Ridley.
AB  - Eight new marine steroids, characterized by either the presence of an aromatic
      ring or a cross-conjugated dienone system in ring A, were isolated from the
      Hainan soft coral Dendronephthya studeri Ridley. Their structures were elucidated
      on the basis of detailed spectroscopic analysis and by comparison of their NMR
      data with those reported in the literature.

PMID- 21192716
TI  - alpha-Amylase and lipase inhibitory activity and structural characterization of
      acacia bark proanthocyanidins.
AB  - The bark extract of Acacia mearnsii showed strong lipase and alpha-amylase
      inhibition activities. Fractionation of the extract by column chromatography and
      subsequent (13)C NMR and MALDI-TOF-MS analysis revealed that the active
      substances are proanthocyanidin oligomers mainly composed of 5-deoxyflavan-3-ol
      units. In addition, 4'-O-methylrobinetinidol 3'-O-beta-D-glucopyranoside,
      fisetinidol-(4alpha,6)-gallocatechin, and epirobinetinidol-(4beta,8)-catechin
      were isolated as new compounds, and their structures were determined from
      spectroscopic data. Furthermore, a modified thiol degradation method using
      strongly acidic conditions was applied to the extract to yield three thiol
      degradation products derived from robinetinidol units. This method is useful for
      characterizing acacia proanthocyanidins (wattle tannins).

PMID- 21192717
TI  - Bismuth coordination chemistry with allyl, alkoxide, aryloxide, and
      tetraphenylborate ligands and the {[2,6-(Me2NCH2)2C6H3]2Bi}+ cation.
AB  - A series of bis(aryl) bismuth compounds containing (N,C,N)-pincer ligands, [2,6
      (Me(2)NCH(2))(2)C(6)H(3)](-) (Ar'), have been synthesized and structurally
      characterized to compare the coordination chemistry of Bi(3+) with similarly
      sized lanthanide ions, Ln(3+). Treatment of Ar'(2)BiCl, 1, with
      ClMg(CH(2)CH?CH(2)) affords the allyl complex Ar'(2)Bi(eta(1)-CH(2)CH?CH(2)), 2,
      in which only one allyl carbon atom coordinates to bismuth. Complex 1 reacts with
      KO(t)Bu and KOC(6)H(3)Me(2)-2,6 to yield the alkoxide Ar'(2)Bi(O(t)Bu), 3, and
      aryloxide Ar'(2)Bi(OC(6)H(3)Me(2)-2,6), 4, respectively, but the analogous
      reaction with the larger KOC(6)H(3)(t)Bu(2)-2,6 forms
      [Ar'(2)Bi][OC(6)H(3)(t)Bu(2)-2,6], 6, in which the aryloxide ligand acts as an
      outer sphere anion. Chloride is removed from 1 by NaBPh(4) to form
      [Ar'(2)Bi][BPh(4)], 5, which crystallizes from THF in an unsolvated form with
      tetraphenylborate as an outer sphere counteranion.

PMID- 21192718
TI  - Targeted delivery of nanoparticles to ischemic muscle for imaging and therapeutic
      angiogenesis.
AB  - Targeting of nanoparticles to ischemic tissues was studied in a murine ischemic
      hindlimb model. Intravenously injected fluorescent nanoparticles allowed ischemia
      targeted imaging of ischemic muscles due to increased permeability of blood
      vessels in hypoxic tissues. Targeting efficiency correlated with blood perfusion
      after induction of ischemia and was enhanced in early stages of ischemia (<7
      days). Therapeutic delivery of vascular endothelial growth factor (VEGF) was
      achieved by VEGF-conjugated nanoparticles and resulted in a 1.7-fold increase in
      blood perfusion, as compared to control mice. This work supports the application
      of nanoparticles as imaging and therapeutic modalities for ischemia treatment.

PMID- 21192719
TI  - Monofluorovinyl tosylate: a useful building block for the synthesis of terminal
      vinyl monofluorides via Suzuki-Miyaura coupling.
AB  - Monofluorovinyl tosylate was developed as a practical vinyl fluoride building
      block to couple with a variety of arylboronic acids in the presence of a
      palladium catalyst. The high stereoselectivity of 2-aryl-1-fluoroethene
      derivatives was achieved. This approach is also applicable to the synthesis of
      2,2-diaryl-1-fluoroethenes in good yields.

PMID- 21192720
TI  - Rapid nondestructive spectrometric measurement of temperature-dependent gas
      liquid solubility equilibria.
AB  - Gas-liquid solubility equilibria (Henry's Law behavior) are of basic interest to
      many different areas. Temperature-dependent aqueous solubilities of various
      organic compounds are of fundamental importance in many branches of environmental
      science. In a number of situations, the gas/dissolved solute of interest has
      characteristic spectroscopic absorption that is distinct from that of the
      solvent. For such cases, we report facile nondestructive rapid measurement of the
      temperature-dependent Henry's law constant (K(H)) in a static sealed
      spectrometric cell. Combined with a special cell design, multiwavelength
      measurement permits a large range of K(H) to be spanned. It is possible to derive
      the K(H) values from the absorbance measured in the gas phase only, the liquid
      phase only (preferred), and both phases. Underlying principles are developed, and
      all three approaches are illustrated for a solute like acetone in water. A
      thermostatic spectrophotometer cell compartment, widely used and available,
      facilitates rapid temperature changes and allows rapid temperature-dependent
      equilibrium measurements. Applicability is shown for both acetone and methyl
      isobutyl ketone. Very little sample is required for the measurement; the K(H) for
      4-hydroxynonenal, a marker for oxidative stress, is measured to be 56.9 +/- 2.6
      M/atm (n = 3) at 37.4  degrees C with 1 mg of the material available.

PMID- 21192721
TI  - Amphiphilic amylose-g-poly(meth)acrylate copolymers through "click" onto grafting
      method.
AB  - Periodate oxidation and subsequent reductive amination with propargylamine was
      adopted for the controlled functionalization of amylose with alkyne groups,
      whereas ATRP polymerization was exploited to obtain end-(alpha)- or end-(omega)
      azide functionalized poly(meth)acrylates to be used as "click" reagents in Cu(I)
      catalyzed azide-alkyne [3 + 2] dipolar cycloaddition. Amylose was effectively
      grafted with poly(n-butyl acrylate), poly(n-butyl methacrylate), poly(n-hexyl
      methacrylate), and poly(dimethylaminoethyl methacrylate) with this strategy.
      Their structure and composition were confirmed by FT-IR, NMR spectroscopies, and
      thermogravimetric analysis (TGA). Dynamic and static light scattering analyses,
      as well as TEM microscopy showed that the most amphiphilic among these hybrid
      graft copolymers self-assembled in water, yielding nanoparticles with ca. 30 nm
      diameter.

PMID- 21192722
TI  - Insecticidal activity of rhamnolipid isolated from pseudomonas sp. EP-3 against
      green peach aphid (Myzus persicae).
AB  - Microorganisms capable of growth on oils are potential sources of biopesticides,
      as they produce complex molecules such as biosurfactants and lipopeptides. These
      molecules have antimicrobial activity against plant pathogens, but few data are
      available on their insecticidal activity. The present study describes the
      insecticidal activity of a rhamnolipid isolated from diesel oil-degrading
      Pseudomonas sp. EP-3 (EP-3). The treatment of cell-free supernatants of EP-3
      grown on glucose-mineral medium for 96 h led to > 80% mortality of aphids (Myzus
      persicae) within 24 h. Bioassay-guided chromatography coupled with matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MADLDI-TOF
      MS) and (1H, 13C) nuclear magnetic resonance (NMR) analyses was employed to
      isolate and identify the EP-3 insecticidal metabolites. Dirhamnolipid, with
      molecular formulas of C32H58O13 and C34H62O13, was identified as a main
      metabolite exhibiting insecticidal activity against aphids. Dirhamnolipid showed
      a dose-dependent mortality against aphids, producing about 50% mortality at 40
      MUg/mL and 100% mortality at 100 MUg/mL. Microscopy analyses of aphids treated
      with dirhamnolipid revealed that dirhamnolipid caused insect death by affecting
      cuticle membranes. This is the first report of rhamnolipid as an insecticidal
      metabolite against M. persicae. Rhamnolipid shows potential for use as a
      pesticide to control agricultural pests.

PMID- 21192723
TI  - Bundling and aggregation of DNA by cationic dendrimers.
AB  - Dendrimers are unique synthetic macromolecules of nanometer dimensions with a
      highly branched structure and globular shape. Among dendrimers, polyamidoamine
      (PAMAM) have received most attention as potential transfection agents for gene
      delivery, because these macromolecules bind DNA at physiological pH. The aim of
      this study was to examine the interaction of calf-thymus DNA with several
      dendrimers of different compositions, such as mPEG-PAMAM (G3), mPEG-PAMAM (G4),
      and PAMAM (G4) at physiological conditions, using constant DNA concentration and
      various dendrimer contents. FTIR, UV-visible, and CD spectroscopic methods, as
      well as atomic force microscopy (AFM), were used to analyze the macromolecule
      binding mode, the binding constant, and the effects of dendrimer complexation on
      DNA stability, aggregation, condensation, and conformation. Structural analysis
      showed a strong dendrimer-DNA interaction via major and minor grooves and the
      backbone phosphate group with overall binding constants of K(mPEG-G3) = 1.5 (+/
      0.5) * 10(3) M(-1), K(mPEG-G4) = 3.4 (+/-0.80) * 10(3) M(-1), and K(PAMAM-G4) =
      8.2 (+/-0.90) * 10(4) M(-1). The order of stability of polymer-DNA complexation
      is PAMAM-G4 > mPEG-G4 > mPEG-G3. Both hydrophilic and hydrophobic interactions
      were observed for dendrimer-DNA complexes. DNA remained in the B-family
      structure, while biopolymer particle formation and condensation occurred at high
      dendrimer concentrations.

PMID- 21192724
TI  - Ab initio study of the F + CH3NHNH2 reaction mechanism.
AB  - The F + CH(3)NHNH(2) reaction mechanism is studied based on ab initio quantum
      chemistry methods as follows: the minimum energy paths (MEPs) are computed at the
      UMP2/6-311++G(d,p) level; the geometries, harmonic vibrational frequencies, and
      energies of all stationary points are predicted at the same level of theory;
      further, the energies of stationary points and the points along the MEPs are
      refined by UCCSD(T)/6-311++g(3df,2p). The ab initio study shows that, when the F
      atom approaches CH(3)NHNH(2), the heavy atoms, namely N and C atoms, are the
      favorable combining points. For the two N atoms, two prereaction complexes with
      C(s) symmetry are generated and there exists seven possible subsequent reaction
      routes, of which routes 1, 2, 5, and 7 are the main channels. Routes 1, 2, and 5
      are associated with HF elimination, with H from the amino group or imido group,
      and route 7 involves the N-N bond break. Routes 3 and 6 with relation to HF
      elimination with H from methyl, and route 4 involved the C-N bond break, are all
      energetically disfavored. For the C atom, the attack of F results in the break of
      the C-N bond and the products are CH(3)F + NHNH(2). This route is very
      competitive.

PMID- 21192725
TI  - Primary reactions of bacteriophytochrome observed with ultrafast mid-infrared
      spectroscopy.
AB  - Phytochromes are red-light photoreceptor proteins that regulate a variety of
      responses and cellular processes in plants, bacteria, and fungi. The phytochrome
      light activation mechanism involves isomerization around the C(15)?C(16) double
      bond of an open-chain tetrapyrrole chromophore, resulting in a flip of its D
      ring. In an important recent development, bacteriophytochrome (Bph) has been
      engineered for use as a fluorescent marker in mammalian tissues. Bphs covalently
      bind a biliverdin (BV) chromophore, naturally abundant in mammalian cells. Here,
      we report an ultrafast time-resolved mid-infrared spectroscopic study on the Pr
      state of two highly related Bphs from Rps. palustris , RpBphP2 (P2) and RpBphP3
      (P3) with distinct photoconversion and fluorescence properties. We observed that
      the BV excited state of P2 decays in 58 ps, while the BV excited state of P3
      decays in 362 ps. By combining ultrafast mid-IR spectroscopy with FTIR
      spectroscopy on P2 and P3 wild type and mutant proteins, we demonstrate that the
      hydrogen bond strength at the ring D carbonyl of the BV chromophore is
      significantly stronger in P3 as compared to P2. This result is consistent with
      the X-ray structures of Bph, which indicate one hydrogen bond from a conserved
      histidine to the BV ring D carbonyl for classical bacteriophytochromes such as
      P2, and one or two additional hydrogen bonds from a serine and a lysine side
      chain to the BV ring D carbonyl for P3. We conclude that the hydrogen-bond
      strength at BV ring D is a key determinant of excited-state lifetime and
      fluorescence quantum yield. Excited-state decay is followed by the formation of a
      primary intermediate that does not decay on the nanosecond time scale of the
      experiment, which shows a narrow absorption band at ~1540 cm(-1). Possible
      origins of this product band are discussed. This work may aid in rational
      structure- and mechanism-based conversion of BPh into an efficient near-IR
      fluorescent marker.

PMID- 21192726
TI  - Versatile and iodine atom-economic co-iodination of alkenes.
AB  - Molecular iodine, I(2), is readily converted into 2 equiv of acetyl hypoiodite
      (CH(3)CO(2)I) via oxidation by (diacetoxyiodo)benzene (DAIB) followed by trapping
      of the iodide ion by acetoxyphenyl iodonium ion formed. The in situ generated
      CH(3)CO(2)I is utilized for the synthesis of 1,2-iodo-cofunctionalized
      derivatives of a variety of alkenes. Conversion of both iodine atoms of I(2) to
      I(+) sources results in 100% iodine atom economy for the reported iodo
      cofunctionalization of alkenes.

PMID- 21192727
TI  - Characterization of the lnmKLM genes unveiling key intermediates for beta
      alkylation in leinamycin biosynthesis.
AB  - Leinamycin (LNM, 1) biosynthesis is proposed to involve beta-alkylation of the
      polyketide intermediate, catalyzed by LnmKLM. Inactivation of lnmK, lnmL, or lnmM
      afforded mutant strains that accumulated LNM K-1 (2), K-2 (3), K-3 (4), and
      isomers LNM K-1' (5), K-2' (6), and K-3' (7) whose polyketide origin was
      established by feeding experiments with sodium [1-(13)C]acetate. These findings
      confirm the indispensability of LnmKLM in 1 biosynthesis and suggest that beta
      alkylation proceeds on the growing polyketide intermediate while bound to the LNM
      polyketide synthase.

PMID- 21192728
TI  - A variable column length strategy to expedite method development.
AB  - A variable length method development (or VL-MD)strategy, exploiting the potential
      of an automatic column coupling system, is proposed and has been applied to a
      number of different pharmaceutical and environmental samples with a varying
      degree of complexity. The proposed strategy consistently produced separation
      methods that had at least an equally good critical pair resolution and an equally
      short run time to those of methods produced using commercially available MD
      assistance software. In some cases, the VL-MD strategy allowed the MD time to be
      drastically shortened from >30 h to an overnight run of only 12 h. The developed
      strategy has the potential to become fully automated provided that reliable
      chromatogram read-out software becomes available. The advantage of combining
      different stationary phase types to improve the available selectivity and the
      integration into the general VL-MD strategy was also demonstrated.

PMID- 21192729
TI  - Screening natural products for inhibitors of quinone reductase-2 using
      ultrafiltration LC-MS.
AB  - Inhibitors of quinone reductase-2 (NQO2; QR-2) can have antimalarial activity and
      antitumor activities or can function as chemoprevention agents by preventing the
      metabolic activation of toxic quinones such as menadione. To expedite the search
      for new natural product inhibitors of QR-2, we developed a screening assay based
      on ultrafiltration liquid chromatography-mass spectrometry that is compatible
      with complex samples such as bacterial or botanical extracts. Human QR-2 was
      prepared recombinantly, and the known QR-2 inhibitor, resveratrol, was used as a
      positive control and as a competitive ligand to eliminate false positives.
      Ultrafiltration LC-MS screening of extracts of marine sediment bacteria resulted
      in the discovery of tetrangulol methyl ether as an inhibitor of QR-2. When
      applied to the screening of hop extracts from the botanical, Humulus lupulus L.,
      xanthohumol and xanthohumol D were identified as ligands of QR-2. Inhibition of
      QR-2 by these ligands was confirmed using a functional enzyme assay. Furthermore,
      binding of xanthohumol and xanthohumol D to the active site of QR-2 was confirmed
      using X-ray crystallography. Ultrafiltration LC-MS was shown to be a useful assay
      for the discovery of inhibitors of QR-2 in complex matrixes such as extracts of
      bacteria and botanicals.

PMID- 21192730
TI  - Determining antibody stoichiometry using time-integrated fluorescence cumulant
      analysis.
AB  - We applied fluorescence fluctuation spectroscopy to resolve the binding
      heterogeneity of fluorescently labeled ligand derived from brain natriuretic
      peptide (BNP), a widely used diagnostic marker of heart failure, to a
      corresponding monoclonal antibody. This system includes three species: (1) free
      ligand molecules, (2) antibody with a single site occupied, and (3) antibody with
      both sites occupied. The method we used, time-integrated fluorescence cumulant
      analysis (TIFCA), utilizes cumulants of fluorescence fluctuations to resolve
      subpopulations of multiple fluorescent species freely diffusing in a solution.
      The values of the cumulants depend on the concentration, molecular brightness and
      diffusion time of the fluorescent molecules. The number of molecules in each
      species reflects the antibody affinity. We apply TIFCA to successfully establish
      the stoichiometry of the system, estimate affinity, and identify the presence of
      an inactive fraction of antigen in a single titration experiment.

PMID- 21192731
TI  - Membranes of cationic gemini lipids based on cholesterol with hydroxyl headgroups
      and their interactions with DNA and phospholipid.
AB  - Two series of cholesterol-based cationic gemini lipids with and without hydroxyl
      functions at the headgroups possessing different lengths of polymethylene [
      (CH(2))(n)-] (n = 3, 4, 5, 6, 12) spacer have been synthesized. Each gemini lipid
      formed stable suspension in water. The suspensions of these gemini lipids in
      water were investigated using transmission electron microscopy, dynamic light
      scattering, zeta potential measurements and X-ray diffraction to characterize the
      nature of the individual aggregates formed therein. The aggregation properties of
      these gemini lipids in water were found to strongly depend upon the length of the
      spacer and the presence of hydroxyl group at the headgroup region. Lipoplex
      formation (DNA binding) and the release of the DNA from such lipoplexes were
      performed to understand the nature of interactions that prevail between these
      cationic cholesterol aggregates and duplex DNA. The interactions between such
      gemini lipids and DNA depend both on the presence of OH on the headgroups and the
      spacer length between the headgroups. Finally, we studied the effect of
      incorporation of each cationic gemini lipid into dipalmitoyl phosphatidylcholine
      vesicles using differential scanning calorimetry. The properties of the resulting
      mixed membranes were found again to depend upon the nature of the headgroup and
      the spacer chain length.

PMID- 21192732
TI  - Ultrafast forward and backward electron transfer dynamics of coumarin 337 in
      hydrogen-bonded anilines as studied with femtosecond UV-pump/IR-probe
      spectroscopy.
AB  - Femtosecond infrared spectroscopy is used to study both forward and backward
      electron transfer (ET) dynamics between coumarin 337 (C337) and the aromatic
      amine solvents aniline (AN), N-methylaniline (MAN), and N,N-dimethylaniline
      (DMAN), where all the aniline solvents can donate an electron but only AN and MAN
      can form hydrogen bonds with C337. The formation of a hydrogen bond with AN and
      MAN is confirmed with steady state FT-IR spectroscopy, where the C?O stretching
      vibration is a direct marker mode for hydrogen bond formation. Transient IR
      absorption measurements in all solvents show an absorption band at 2166 cm(-1),
      which has been attributed to the C=N stretching vibration of the C337 radical
      anion formed after ET. Forward electron transfer dynamics is found to be
      biexponential with time constants tau(ET)(1) = 500 fs, tau(ET)(2) = 7 ps in all
      solvents. Despite the presence of hydrogen bonds of C337 with the solvents AN and
      MAN, no effect has been found on the forward electron transfer step. Because of
      the absence of an H/D isotope effect on the forward electron transfer reaction of
      C337 in AN, hydrogen bonds are understood to play a minor role in mediating
      electron transfer. In contrast, direct pi-orbital overlap between C337 and the
      aromatic amine solvents causes ultrafast forward electron transfer dynamics.
      Backward electron transfer dynamics, in contrast, is dependent on the solvent
      used. Standard Marcus theory explains the observed backward electron transfer
      rates.

PMID- 21192733
TI  - Structure and gas sorption behavior of a new three dimensional porous magnesium
      formate.
AB  - A new three-dimensional magnesium formate polymorph, namely, gamma
      [Mg(3)(O(2)CH)(6)] has been synthesized via in situ formate anion generation
      method. gamma-Mg-formate crystallizes in space group Pbcn, and structural
      determination by X-ray single crystal diffraction reveals a three-dimensional
      network of Mg(2+) linked by formate anions. All formate anions possess similar
      binding mode to the metal center with one oxygen of a particular formate anion
      binds to one metal center (MU(1) oxygen) and other oxygen binds to two metal
      centers (MU(2) oxygen). N(2) adsorption studies indicate that the framework
      displays permanent porosity. The specific surface area of gamma-Mg-formate (BET,
      120 m(2) gm(-1)) is lower than the alpha- polymorph (BET, 150 m(2) gm(-1)).
      However, the initial hydrogen uptake of gamma-Mg-formate reached almost 1.0 wt %
      when the adsorbate pressure approached 760 Torr at 77 K. This is higher than the
      hydrogen uptake of alpha-Mg-formate (0.6 wt %). gamma-Mg-formate, shows a
      moderate affinity and capacity for CO(2) (3.4 A kinetic diameter) at 298 K. The
      CO(2) uptake at 760 Torr is 2.01 mmol gm(-1) (47.0 cc gm(-1)). Although this
      CO(2) uptake is somewhat modest, it compares well with the CO(2) uptake of
      several Mg-MOFs and ZIFs reported in the literature.

PMID- 21192734
TI  - Class modeling analysis of heparin 1H NMR spectral data using the soft
      independent modeling of class analogy and unequal class modeling techniques.
AB  - To differentiate heparin samples with varying amounts of dermatan sulfate (DS)
      impurities and oversulfated chondroitin sulfate (OSCS) contaminants, proton NMR
      spectral data for heparin sodium active pharmaceutical ingredient samples from
      different manufacturers were analyzed using multivariate chemometric techniques.
      A total of 168 samples were divided into three groups: (a) Heparin, [DS] <= 1.0%
      and [OSCS] = 0%; (b) DS, [DS] > 1.0% and [OSCS] = 0%; (c) OSCS, [OSCS] > 0% with
      any content of DS. The chemometric models were constructed and validated using
      two well-established methods: soft independent modeling of class analogy (SIMCA)
      and unequal class modeling (UNEQ). While SIMCA modeling was conducted using the
      entire set of variables extracted from the NMR spectral data, UNEQ modeling was
      combined with variable reduction using stepwise linear discriminant analysis to
      comply with the requirement that the number of samples per class exceed the
      number of variables in the model by at least 3-fold. Comparison of the results
      from these two modeling approaches revealed that UNEQ had greater sensitivity
      (fewer false positives) while SIMCA had greater specificity (fewer false
      negatives). For Heparin, DS, and OSCS, respectively, the sensitivity was 78%
      (56/72), 74% (37/50), and 85% (39/46) from SIMCA modeling and 88% (63/72), 90%
      (45/50), and 91% (42/46) from UNEQ modeling. Importantly, the specificity of both
      the SIMCA and UNEQ models was 100% (46/46) for Heparin with respect to OSCS; no
      OSCS-containing sample was misclassified as Heparin. The specificity of the SIMCA
      model (45/50, or 90%) was superior to that of the UNEQ model (27/50, or 54%) for
      Heparin with respect to DS samples. However, the overall prediction ability of
      the UNEQ model (85%) was notably better than that of the SIMCA model (76%) for
      the Heparin vs DS vs OSCS classes. The models were challenged with blends of
      heparin spiked with nonsulfated, partially sulfated, or fully oversulfated
      chondroitin sulfate A, dermatan sulfate, or heparan sulfate at the 1.0, 5.0, and
      10.0 wt % levels. The results from the present study indicate that the
      combination of (1)H NMR spectral data and class modeling techniques (viz., SIMCA
      and UNEQ) represents a promising strategy for assessing the quality of commercial
      heparin samples with respect to impurities and contaminants. The methodologies
      show utility for applications beyond heparin to other complex products.

PMID- 21192736
TI  - Synthesis of molluscicidal agent cyanolide a macrolactone from D-(-)
      pantolactone.
AB  - An efficient synthesis of potent molluscicidal agent cyanolide A, a glycosidic 16
      membered macrolide, starting from D-(-)-pantolactone is reported. Highly
      stereoselective aldol, oxa-Michael addition, and Yamaguchi macrolactonization are
      the key steps in the present synthesis.

PMID- 21192735
TI  - Unusual heme binding in the bacterial iron response regulator protein: spectral
      characterization of heme binding to the heme regulatory motif.
AB  - We characterized heme binding in the bacterial iron response regulator (Irr)
      protein, which is a simple heme-regulated protein having a single "heme
      regulatory motif", HRM, and plays a key role in the iron homeostasis of a
      nitrogen-fixing bacterium. The heme titration to wild-type and mutant Irr clearly
      showed that Irr has two heme binding sites: one of the heme binding sites is in
      the HRM, where (29)Cys is the axial ligand, and the other one, the secondary heme
      binding site, is located outside of the HRM. The Raman line for the Fe-S
      stretching mode observed at 333 cm(-1) unambiguously confirmed heme binding to
      Cys. The lower frequency of the Fe-S stretching mode corresponds to the weaker Fe
      S bond, and the broad Raman line of the Fe-S bond suggests multiple
      configurations of heme binding. These structural characteristics are definitely
      different from those of typical hemoproteins. The unusual heme binding in Irr was
      also evident in the EPR spectra. The characteristic g-values of the 5-coordinate
      Cys-ligated heme and 6-coordinate His/His-ligated heme were observed, while the
      multiple configurations of heme binding were also confirmed. Such multiple heme
      configurations are not encountered for typical hemoproteins where the heme
      functions as the active center. Therefore, we conclude that heme binding to HRM
      in the heme-regulated protein, Irr, is quite different from that in conventional
      hemoproteins but characteristic of heme-regulated proteins using heme as the
      signaling molecule.

PMID- 21192737
TI  - Chlamydia pneumoniae heat shock protein 60 enhances expression of ERK, TLR-4 and
      IL-8 in atheromatous plaques of coronary artery disease patients.
AB  - Chlamydia pneumoniae heat shock protein (cHSP) 60 is produced during chronic
      chlamydial infection and activate innate immune and inflammatory responses
      thereby contributing to atherogenesis. However, to date there is no apparent
      signaling cascade delineated in human atherosclerotic plaques in C. pneumoniae
      positive coronary artery disease (CAD) patients. Atherosclerotic plaques were
      obtained from 40 CAD patients (28 men, 12 women) attending Department of Cardio
      Thoracic and Vascular Surgery Safdarjung Hospital, New Delhi. Atherosclerotic
      plaques were used for gene expression studies at RNA level by real-time PCR and
      to study expression of ERK1/2, JNK1/2, NF-kB, IkkB and MCP-1 at protein level by
      immunoblotting. Significantly higher (p < 0.001) RNA expression was found for IL
      8, TLR-2/4, TGF-beta, ICAM1, VCAM1 and MAPKinase genes, whereas significantly
      lower (p < 0.001) RNA expression for SMAD4, IkkB, BRCA1 and IL-10 was detected in
      cHSP60-positive atheromatous plaque of CAD patients. Moreover, at proteins level
      pERK1/2 (p = 0.05), NF-kB (p = 0.017), MCP-1 (p = 0.011) was higher and IkkB
      expression was lower (p = 0.038) in cHSP60-positive atheromatous plaque of CAD
      patients. This study by using human atheromatous plaques at RNA and protein
      levels demonstrated higher expression of TLR-2/4, IL-8, ICAM1, VCAM1, ERK1/2 and
      NF-kB in cHSP60-positive CAD patients.

PMID- 21192738
TI  - Evidence-based programming: a practitioner's guide.

PMID- 21192739
TI  - Peers, tobacco advertising, and secondhand smoke exposure influences smoking
      initiation in diverse adolescents.
AB  - PURPOSE: Identify demographic, social, and environmental factors associated with
      smoking initiation in a large, racially and ethnically diverse sample of underage
      youth participating in the 2006 Maryland Youth Tobacco Survey. DESIGN: Cross
      sectional, multistage, probability sample survey. SETTING: Schools (308 middle
      and high schools) in Maryland. SUBJECTS: Subjects were 12- to 17-year-old
      adolescents participating in a school-based survey. New smokers and nonsmokers
      were included in the analysis (n  =  57,072). MEASURES: Social and media
      influence, secondhand smoke exposure, tobacco product use, and demographic
      information including age, race/ethnicity, and geographic region. ANALYSIS: Chi
      square and multiple logistic regression analyses controlling for clustering.
      RESULTS: Hispanic and Hawaiian/Pacific Islander youth were most likely and Asian
      and Black youth were least likely to be new smokers. Smoking initiation was
      positively associated with higher age, living with a current smoker, secondhand
      smoke exposure, exposure to advertisements for tobacco products, having more
      friends that smoke, tobacco products offered by friends, risk perceptions, and
      use of other tobacco products such as smokeless tobacco and cigars. Multivariate
      logistic regression results suggested that composite measures of peer influence,
      advertising exposure, and secondhand smoke exposure were independently associated
      with smoking initiation. CONCLUSIONS: Media, peer influence, and secondhand smoke
      exposure were the most important factors influencing smoking initiation and were
      common to all racial/ethnic groups in this study. Interventions combining
      targeted public awareness, education, and media campaigns directed at
      parents/guardians should be investigated.

PMID- 21192740
TI  - Promising practices for the prevention and control of obesity in the worksite.
AB  - PURPOSE: To identify worksite practices that show promise for promoting employee
      weight loss. DATA SOURCE: The following electronic databases were searched from
      January 1, 1966, through December 31, 2005: CARL Uncover (via Ingenta), CDP,
      CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Library, CRISP,
      Dissertation Abstracts, EMBASE, ERIC, Health Canada, INFORM (part of ABI/INFORM
      Proquest), LocatorPlus, New York Academy of Medicine, Ovid MEDLINE, SPORTDiscus,
      PapersFirst, PsycINFO, PubMed, and TRIP. STUDY INCLUSION AND EXCLUSION CRITERIA:
      Included studies were published in English, conducted at a worksite, designed for
      adults (aged >= 18 years), and reported weight-related outcomes. DATA EXTRACTION:
      Data were extracted using an online abstraction form. DATA SYNTHESIS: Studies
      were evaluated on the basis of study design suitability quality of execution,
      sample size, and effect size. Changes in weight-related outcomes were used to
      assess effectiveness. RESULTS: The following six promising practices were
      identified: enhanced access to opportunities for physical activity combined with
      health education, exercise prescriptions alone, multicomponent educational
      practices, weight loss competitions and incentives, behavioral practices with
      incentives, and behavioral practices without incentives. CONCLUSIONS: These
      practices will help employers and employees select programs that show promise for
      controlling and preventing obesity.

PMID- 21192741
TI  - Active commuting and habit strength: an interactive and discriminant analyses
      approach.
AB  - PURPOSE: Habits may be a mechanism linking environmental variables with active
      commuting. This study investigated the role of habit strength in the explanation
      of active commuting across profiles based on current active commuting,
      motivation, and habit strength within the framework of the theory of planned
      behavior (TPB). DESIGN: Cross-sectional survey using validated questionnaires.
      SETTING: Undergraduate students who participated for course credits. SUBJECTS:
      Five hundred and thirty-eight students (mean age  =  21.19 [SD  =  2.57]; 28.45%
      males; response rate  =  86.36%). MEASURES: Questionnaire included TPB items,
      underlying beliefs, and a validated measure of habit strength. Active commuting
      was assessed with relevant items from the International Physical Activity
      Questionnaire. ANALYSIS: Hierarchical regression and interaction analyses,
      discriminant function analysis, and analyses of variance. RESULTS: Habit strength
      was the strongest correlate of active commuting and interacted with intention: at
      low and medium levels of habit strength, the intention-bicycle use relationship
      was more than twice as strong as at high levels. Beliefs regarding situational
      barriers were amongst the most discriminating beliefs, whereas beliefs regarding
      health benefits did not distinguish profiles. CONCLUSIONS: Stronger active
      commuting habits are associated with a lower association between intention and
      bicycle use. Persuasive health campaigns might more usefully instill a sense of
      confidence in various commuting situations rather than merely emphasizing health
      benefits of active commuting.

PMID- 21192742
TI  - CDC will help employers evaluate their health promotion programs and will conduct
      periodic national surveys on workplace health promotion programs.

PMID- 21192743
TI  - Deception of trans fats on Food and Drug Administration food labels: a proposed
      revision to the presentation of trans fats on food labels.

PMID- 21192744
TI  - A longitudinal study of the family physical activity environment and physical
      activity among youth.
AB  - PURPOSE: Although the family environment is a potentially important influence on
      children's physical activity (PA), prospective data investigating these
      associations are lacking. This study aimed to examine the longitudinal
      relationship between the family environment and PA among youth. DESIGN: A 5-year
      prospective cohort study. SETTING: Nineteen randomly selected public schools in
      Melbourne, Australia. SUBJECTS: Families of 5- to 6-year-old (n  =  190) and 10-
      to 12-year-old (n  =  350) children. MEASURES: In 2001, parents reported their
      participation in PA, family-based PA, and support and reinforcement for their
      child's PA. In 2001, 2004, and 2006, moderate to vigorous intensity PA (MVPA) was
      assessed among youth using accelerometers. Weekend and "critical window" (after
      school until 6:00 p.m.) MVPA were examined because we hypothesized that the
      family environment would most likely influence these behaviors. ANALYSIS:
      Generalized estimating equations predicted average change in MVPA over 5 years
      from baseline family environment factors. RESULTS: Maternal role modeling was
      positively associated with boys' critical window and weekend (younger boys) MVPA.
      Paternal reinforcement of PA was positively associated with critical window and
      weekend MVPA among all boys, and paternal direct support was positively
      associated with weekend MVPA (older boys). Among girls, maternal coparticipation
      in PA predicted critical window MVPA, and sibling coparticipation in PA was
      directly associated with weekend MVPA (younger girls). CONCLUSIONS: Longitudinal
      relationships, although weak in magnitude, were observed between the family
      environment and MVPA among youth. Interventions promoting maternal role modeling,
      paternal reinforcement of and support for PA, and maternal and sibling
      coparticipation in PA with youth are warranted.

PMID- 21192745
TI  - A faith-based physical activity intervention for Latinos: outcomes and lessons.
AB  - PURPOSE: To develop, implement, and evaluate a pilot faith-based physical
      activity (PA) intervention for Latinos. DESIGN: Randomized trial, with two
      churches receiving the intervention and one church serving as a comparison group.
      SETTING: Three Catholic churches near Manhattan, Kansas. SUBJECTS: A subsample of
      the congregation from the intervention churches (n  =  24) and comparison church
      (n  =  23) volunteered to take part in the assessment. INTERVENTION: Culturally
      and spiritually relevant education materials and activities were developed
      promoting the health benefits of PA. Educational materials included flyers,
      bulletin inserts, and posters. An 8-week team based walking contest promoted
      social support for PA. A health "fiesta" provided hands-on educational
      opportunities for PA. MEASURES: Organizational and individual process evaluation
      outcomes were assessed at baseline and 6 months. Interviews with church contacts
      at 6 months documented successes and struggles with implementation. Individual
      level variables assessed knowledge related to PA and exposure to the
      intervention. ANALYSIS: Basic frequencies and descriptive statistics were used.
      RESULTS: Compared with 36% of comparison participants, 66% of intervention
      participants identified health reasons for participating in PA, and 47%
      accurately described PA recommendations, compared with 16% of comparison
      participants. Process evaluation revealed implementation successes and struggles,
      including communication problems with church contacts and difficulty in creating
      a large exposure to intervention materials. CONCLUSIONS: This pilot study
      provides formative research for developing larger faith-based PA interventions
      targeting Latinos.

PMID- 21192746
TI  - A pilot walking program for Mexican-American women living in colonias at the
      border.
AB  - PURPOSE: To test the effectiveness of !Vamos a Caminar! (Let's Walk!), an
      intervention for Mexican-American women living in economically disadvantaged,
      poorly urbanized areas in the South Texas border region. DESIGN: This was a
      nonexperimental, one-group, pretest and posttest intervention with a duration of
      12 weeks. SETTING: The intervention was conducted in Hidalgo County, Texas, 1 of
      the 10 poorest counties in the United States, located at the border with Mexico.
      Participants resided in areas known as colonias, which are unincorporated and
      impoverished settlements along the border where many people live in trailers or
      self-built houses and lack basic services. SUBJECTS: Spanish-speaking Mexican
      American women (n  =  16) 18 years of age and older. INTERVENTION: The program
      was home-based, culturally sensitive, theoretically driven, and facilitated by
      community health workers. MEASURES: Changes in walking levels, depressive
      symptoms, and stress levels were assessed. ANALYSIS: Descriptive statistics and
      the Wilcoxon matched-pairs signed-ranks test were used. RESULTS: A majority of
      participants were unemployed, had low levels of education, were born in Mexico,
      and were obese. After exposure to the program, the participants reported a
      significant increase in walking (915.8 metabolic equivalent min/wk; p  =  .002)
      and lower depressive symptoms (p  =  .055) and stress level scores (p  =  .017).
      CONCLUSIONS: Culturally sensitive programs promoting walking in underserved,
      minority populations are promising in reducing physical activity disparities.

PMID- 21192747
TI  - The impact of state tobacco control program funding cuts on teens' exposure to
      tobacco control interventions: evidence from Florida.
AB  - PURPOSE: Explore the impact of dramatic budget cuts to the Florida Tobacco
      Control Program (FTCP) on Florida teens' exposure to tobacco control
      interventions. DESIGN: Survey data on teens in Florida and a comparison sample of
      the remainder of the United States. Data were collected in six waves between 2002
      and 2006, with three waves collected before and three waves collected after the
      FTCP budget cut in fiscal year (FY) 2004. SETTING: Florida. SUBJECTS: Twelve- to
      17-year-old teens in Florida and the remainder of the United States. Between
      spring 2002 and summer 2006, 7841 interviews of Florida teens and 10,875
      interviews of teens in the remainder of the United States were conducted.
      MEASURES: Exposure to FTCP interventions, including tobacco countermarketing,
      school and community organizations, and in-school tobacco prevention curricula.
      ANALYSIS: Multivariable logistic regression models were used to test whether
      declines in Florida youth's exposure to FTCP interventions were associated with
      the FTCP budget cut. RESULTS: Following the FY2004 FTCP budget cut, there were
      greater declines in teens' exposure to tobacco countermarketing campaigns in
      Florida compared with the remainder of the United States (odds ratio [OR]  = 
      .42; p < .001). The FY2004 budget cut also may have had an impact on exposure to
      in-school tobacco prevention curricula and school youth organizations (OR  = 
      .67; p < .001). CONCLUSION: Program budget cuts in Florida resulted in
      significant declines in exposure to some FTCP interventions (particularly tobacco
      countermarketing). Research on the correlates of smoking suggests that these
      budget cuts could have a significant impact on tobacco-related outcomes among
      teens.

PMID- 21192748
TI  - Effectiveness of a worksite telephone-based weight management program.
AB  - PURPOSE: Examine the long-term impact of a telephone-based weight management
      program among participants recruited from worksite settings. DESIGN: Pre/post
      quasi-experimental design comparing weight loss and related behaviors between
      program completers and noncompleters. SETTING: Ten large private-sector and
      public-sector employers. SUBJECTS: Overweight or obese participants (n  =  1298)
      enrolled in a telephone-based weight management program. INTERVENTION:
      Individually tailored telephone-based weight management coaching program that
      included up to five calls over a median of 250 days. MEASURES: Weight, body mass
      index, and lifestyle behaviors assessed via health risk assessment at baseline
      and 1-year follow-up. ANALYSIS: Chi-square and one-way analysis of variance
      procedures were used to assess between-group differences in weight and associated
      behaviors, with criterion for significance set at p < .05. RESULTS: Among weight
      management program participants, 48% of program completers and 47% of
      noncompleters lost weight, but program completers averaged 2.6 times more weight
      loss than noncompleters. Improvements in physical activity, eating habits, and
      overall health status were reported for completers. CONCLUSION: The weight loss
      attained among participants who lost weight, along with the improvements in
      physical activity and nutrition practices, suggests that a telephone-based weight
      management program of modest intensity can have a positive impact on the health
      of obese or overweight worksite participants.

PMID- 21192749
TI  - Young children's weight trajectories and associated risk factors: results from
      the Early Childhood Longitudinal Study-Birth Cohort.
AB  - PURPOSE: To estimate the prevalence of U.S. children's overweight risk and
      obesity at age 9 months and at age 2 years, to assess weight changes between the
      two periods, and to examine relationships between weight status (i.e., normal, at
      risk, or obese) changes and demographic variables. DESIGN: Analyses of children's
      early weight trajectories and related demographic characteristics from the Early
      Childhood Longitudinal Study-Birth Cohort (ECLS-B) are presented. SETTING: United
      States. SUBJECTS: The 9-month-old (n  =  8900) and 2-year-old (n  =  7500) ECLS-B
      waves were used to generate nationally representative estimates of obese and at
      risk children born in 2001. MEASURES: Measures included child's sex,
      race/ethnicity, socioeconomic status, community locale, geographic region, and
      weight status. ANALYSIS: Logistic and multinomial logistic regression models were
      used to determine the odds of children's demographic characteristics being
      related to weight persistence, loss, or gain. RESULTS: Approximately one-third of
      U.S. children were either at risk or obese at 9 months (31.9%) and at 2 years
      (34.3%). Some children were at greater risk (e.g., Hispanics and low
      socioeconomic status children), while others had reduced risk (e.g., females and
      Asian/Pacific Islanders). Additional results from two trajectory models generally
      corroborated patterns of status change due to weight gain. CONCLUSIONS: Between
      age 9 months and age 2 years, U.S. children consistently moved toward less
      desirable weight status. Obesity risk was not uniform across demographic
      subgroups, suggesting that health policy might focus on those children at
      greatest risk.

PMID- 21192750
TI  - Get moving: a web site that increases physical activity of sedentary employees.
AB  - PURPOSE: Develop and test a Web site to encourage physical activity (PA) by
      sedentary workers. DESIGN: Randomized control design with 30-day follow-up.
      SETTING: Large manufacturing plant. SUBJECTS: Included 221 workers; average body
      mass index was 29.5. INTERVENTION: Get Moving was a repeat-visit Web site
      providing information and support to develop a personalized PA plan. MEASURES:
      Self-reported: PA, depression, anxiety, stage of change, attitudes, knowledge,
      self-efficacy, intention, perceived barriers to PA, and motivation. ANALYSIS:
      Multivariate analysis of covariance and univariate analysis of covariance models
      were used to compare the two study conditions on posttest outcomes, controlling
      for baseline levels. RESULTS: Compared with the control group, the treatment
      group showed significant improvement. The multivariate test was significant (p <
      .001), with a large effect size (eta(2) =  .42). The treatment group differed
      significantly from the control participants on 11 outcomes (p < .005), with large
      effect sizes for PA status, min/d, and knowledge, attitudes, and behavioral
      intention. Medium effect sizes were measured for perceived barriers, depressive
      symptoms, motivation, and self-efficacy. Multiple visits resulted in
      significantly improved PA, motivation, self-efficacy, and intention, compared
      with one-time visits. CONCLUSIONS: The Get Moving Web site had positive effects
      and was well received. Interventions Web site have potential to increase the PA
      of sedentary individuals in worksites and elsewhere, but more research is needed
      into mediators of Web-based interventions.

PMID- 21192751
TI  - Workplace telecommunications technology to identify mental health disorders and
      facilitate self-help or professional referrals.
AB  - PURPOSE: Test the feasibility and impact of an automated workplace mental health
      assessment and intervention. DESIGN: Efficacy was evaluated in a randomized
      control trial comparing employees who received screening and intervention with
      those who received only screening. SETTING: Workplace. SUBJECTS: 463 volunteers
      from Boston Medical Center, Boston University, and EMC and other employed adults,
      among whom 164 were randomized to the intervention (N  =  87) and control (N  = 
      77) groups. INTERVENTION: The system administers a panel of telephonic assessment
      instruments followed by tailored information, education, and referrals. MEASURES:
      The Work Limitation Questionnaire, the Medical Outcomes Questionnaire Short Form
      12, the Patient Health Questionnaire-9, question 10 from the Patient Health
      Questionnaire to measure functional impairment, and the Perceived Stress Scale-4
      and questions written by study psychiatrists to measure emotional distress and
      social support respectively. The WHO-Five Well-being Index was administered to
      measure overall well-being. ANALYSIS: Independent sample t-tests and chi(2) tests
      as well as mean change were used to compare the data. RESULTS: No significant
      differences on 16 of the 20 comparisons at 3- and 6-month time points. The
      intervention group showed a significant improvement in depression (p <= .05) at 3
      months and on two Work Limitation Questionnaire subscales, the Mental
      Interpersonal Scale (p <= .05) and the Time and Scheduling Scale (p <= .05), at 3
      and 6 months respectively with a suggestive improvement in mental health at 6
      months (p <= .10). CONCLUSIONS: This is a potentially fruitful area for research
      with important implications for workplace behavioral interventions.

PMID- 21192754
TI  - Delayed neurological sequelae from ethylene glycol, diethylene glycol and
      methanol poisonings.
AB  - INTRODUCTION: Ethylene glycol, diethylene glycol and methanol are widely
      available chemicals and are found in a variety of common household products
      including antifreeze, windshield washer fluid, brake fluid and lubricants.
      Following ingestion of these glycols and methanol, patients frequently develop an
      early neurological syndrome consisting of inebriation, ataxia, and if severe,
      seizures and coma. Though uncommon, a neurological syndrome may also develop as a
      delayed complication. METHODS: Using Pub Med 438 references were identified of
      which 45 were relevant. FEATURES: Ethylene glycol poisoning has produced cranial
      nerve deficits (usually VII nerve dysfunction) after a delay of 5-20 days,
      Parkinsonism and cerebral edema. Diethylene glycol ingestion has been associated
      with the development of optic nerve injury, cranial nerve deficits, quadraparesis
      and peripheral neuropathy. Methanol poisoning has led to Parkinsonism and
      polyneuropathy. MECHANISMS OF TOXICITY: Oxalate crystal deposition likely causes
      the cranial neuropathies related to ethylene glycol and 2-hydroxyethoxyacetic
      acid is thought to be the causal moiety in cranial neuropathies resulting from
      diethylene glycol toxicity. Formic acid is implicated in the optic nerve damage
      associated with methanol. CONCLUSIONS: Uncommonly, delayed neurological syndromes
      may develop as complications of poisoning due to ethylene glycol, diethylene
      glycol and methanol; the onset of such neurological damage is often days or even
      weeks post-ingestion. Further research is required to explain why the facial
      nerve is the cranial nerve most commonly involved and why the basal ganglia are
      predisposed to injury.

PMID- 21192755
TI  - Usefulness of the serum lactate concentration for predicting mortality in acute
      beta-blocker poisoning.
AB  - CONTEXT: Serum lactate measured in the emergency department was recently assessed
      as an excellent prognosticator of drug-overdose fatality, with the optimal
      lactate cutoff point being 3.0 mmol/L. However, lactate's role has never been
      specifically studied in beta-blocker poisonings. OBJECTIVE: We aimed to evaluate
      the ability of lactate concentrations to predict outcome (survival versus death)
      in beta-blocker poisoning. METHODS: We conducted an 8-year retrospective study
      for all symptomatic beta-blocker poisonings admitted to our toxicological
      intensive care unit (ICU). Serum lactate concentrations were measured in 110
      patients and final outcomes of survival or death recorded. RESULTS: Lactate
      concentrations were 1.79 mmol/L [0.8-5.6] (median, 10-90% percentiles) and peak
      values of 1.9 mmol/L [0.9-9.5] (p < 0.0001). Nine patients (8%) died in the ICU.
      Admission serum lactate concentrations differed significantly between survivors
      and fatalities (p = 0.0008). Four patients (44% of the non-survivors) died in the
      ICU despite lactate concentrations lower than 3.0 mmol/L. The diagnostic
      characteristics of the 3.0 mmol/L selected lactate cutoff point were 55%
      sensitivity and 80% specificity. CONCLUSION: Serum lactate elevation in beta
      blocker poisoning is relatively mild on admission despite the presence of
      significant cardiovascular symptoms. Even if raised in severe poisonings and
      alone correlate well with prognosis, lactate concentration is not an absolute
      predictor of beta-blocker-overdose fatality.

PMID- 21192756
TI  - 2009 Annual Report of the American Association of Poison Control Centers'
      National Poison Data System (NPDS): 27th Annual Report.
AB  - BACKGROUND: This is the 27th Annual Report of the American Association of Poison
      Control Centers' (AAPCC) National Poison Data System (NPDS). As of 1 July 2009,
      60 of the nation's 60 US poison centers (PCs) uploaded case data automatically.
      The upload time was 19.9 [9.7, 58.7] (median [25%, 75%]) minutes, creating a near
      real-time national exposure and information database and surveillance system.
      METHODOLOGY: We analyzed the case data tabulating specific indices from NPDS. The
      methodology was similar to that of previous years. Where changes were introduced,
      the differences are identified. Poison center cases with medical outcomes of
      death were evaluated by a team of 29 medical and clinical toxicologist reviewers
      using an ordinal scale of 1-6 to determine Relative Contribution to Fatality
      (RCF) of the exposure to the death. RESULTS: In 2009, 4,280,391 calls were
      captured by NPDS: 2,479,355 closed human exposures, 116,408 animal exposures,
      1,677,403 information calls, 6,882 human confirmed nonexposures, and 343 animal
      confirmed nonexposures. The top 5 substance classes most frequently involved in
      all human exposures were analgesics (11.7%), cosmetics/personal care products
      (7.7%), household cleaning substances (7.4%), sedatives/hypnotics/antipsychotics
      (5.8%), and foreign bodies/toys/miscellaneous (4.3%). Analgesic exposures as a
      class increased the most rapidly (12,494 calls per year) over the last decade.
      The top 5 most common exposures in children age 5 or less were cosmetics/personal
      care products (13.0%), analgesics (9.7%), household cleaning substances (9.3%),
      foreign bodies/toys/miscellaneous (7.0%), and topical preparations (6.8%). Drug
      identification requests comprised 63.0% of all information calls. NPDS documented
      1,544 human exposures resulting in death with 1,158 human fatalities judged
      related with an RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3
      Contributory. CONCLUSIONS: Unintentional and intentional exposures continue to be
      a significant cause of morbidity and mortality in the US. The near real-time,
      always current status of NPDS represents a national public health resource to
      collect and monitor US exposure cases and information calls. The continuing
      mission of NPDS is to provide a nationwide infrastructure for public health
      surveillance for all types of exposures, public health event identification,
      resilience response and situational awareness tracking. NPDS is a model system
      for the nation and global public health.

PMID- 21192757
TI  - Local effects after inadvertent digital injection with an epinephrine auto
      injector.

PMID- 21192758
TI  - The effects of gatekeeping: a systematic review of the literature.
AB  - OBJECTIVE: To assess the effects of physician-centred gatekeeping on health,
      health care utilization, and costs by conducting a systematic review of the
      literature. METHODS: Systematic search in PubMed (MEDLINE and Pre-MEDLINE),
      EMBASE, and the Cochrane Library, from the databases' respective inception dates
      up to January 2010, using the search words "gatekeeping", "gatekeeper*", "first
      contact", and "self-referral". We included RCTs, CCTs, cohort studies, CBAs, and
      interrupted time-series. We included only studies in which the gatekeeper
      function was exercised by a physician and that reported health and patient
      related outcomes including quality of life and satisfaction, quality of care,
      health care utilization, and/or economic outcomes (e.g. expenditures or
      efficiency). Selection was made independently by two reviewers and discrepancies
      were solved by consensus after discussion. Data on target population,
      intervention, additional interventions, study results, and methodological quality
      were extracted. Methodological quality was assessed independently by two
      reviewers following the previously defined criteria. Discrepancies were solved by
      consensus after discussion. RESULTS: This review includes 26 studies in 32
      publications. The majority of studies (62%) reported data from the United States
      and in most gatekeeping was associated with lower utilization of health services
      (up to -78%) and lower expenditures (up to -80%). However, there was great
      variability in the magnitude and direction of the differences. CONCLUSION:
      Overall, the evidence regarding the effects of gatekeeping is of limited quality.
      Many studies are available regarding the effects on health care utilisation and
      expenditures, whereas effects on health and patient-related outcomes have been
      studied only exceptionally and are inconclusive.

PMID- 21192759
TI  - Clinical and cost outcomes of venous thromboembolism in Medicare patients
      undergoing total hip replacement or total knee replacement surgery.
AB  - BACKGROUND: Venous thromboembolism (VTE) occurs most often during hospitalization
      for major surgery or trauma but may also occur up to several months after
      surgery. Since the potential for VTE exists in a range of clinical settings, an
      assessment of its impact on overall outcomes and costs to the patient and to the
      healthcare system is warranted. OBJECTIVE: To evaluate the effects of VTE (deep
      vein thrombosis, pulmonary embolism, or both) occurring within the first 30 days
      of hospital discharge for total hip replacement (THR) or total knee replacement
      (TKR) surgery on inpatient costs, mortality, rehospitalization, and major
      bleeding within 1 year after initial hospitalization for THR or TKR surgery.
      METHODS: The Medicare Provider Analysis and Review (MEDPAR) file for calendar
      years 2005-2007 provided hospital discharge abstracts for the fee-for-service,
      acute-care hospitalizations of all Medicare recipients. All patients included in
      the analysis underwent THR (n = 51,108) or TKR (n = 115,627). VTE events were
      diagnosed within the first 30 days and within 1 year post discharge. Propensity
      score matching was used to control for differences in baseline characteristics in
      patients with and without VTE events. Total cost was measured as Medicare cost
      plus beneficiary out-of-pocket cost. RESULTS: VTE occurred in 0.74% of patients
      undergoing THR. For patients with VTE versus no VTE, mortality was higher (2.9%
      vs 0.4%, P < 0.001) and rehospitalization within 1 year was more frequent (51.9%
      vs 22.4%, P < 0.001), as were complications such as bleeding (11.2% vs 2.7%, P <
      0.001). Risk-adjusted Medicare cost and total healthcare cost, including
      beneficiary cost share in 1 year, were significantly higher for VTE patients
      versus patients with no VTE ($18,929 vs $3763, P < 0.001). VTE occurred in 0.70%
      of patients undergoing TKR. For patients with VTE versus no VTE, mortality was
      higher (2.5% vs 0.15%, P < 0.001), and rehospitalization within 1 year was more
      frequent (48.7% vs 20.7%, P < 0.001), as were complications such as bleeding
      (13.7% vs 2.1%, P < 0.001). For TKR surgery, risk-adjusted total healthcare cost,
      including beneficiary cost share in 1 year, was significantly different for VTE
      versus no VTE ($17,996 vs $4358, P < 0.001). LIMITATIONS: Study limitations
      include a reliance on ICD-9-CM codes, which could be inaccurate, and the
      inability (1) to control for unmeasured confounders, such as surgeons' skills;
      (2) to include outpatient medical care costs; and (3) to ensure that all patients
      were enrolled continuously throughout the study period. CONCLUSIONS: VTE after
      THR or TKR is associated with higher mortality, rehospitalization, and bleeding
      within 1 year, compared with no VTE. Risk-adjusted total, Medicare, and
      beneficiary healthcare costs were significantly higher for both THR and TKR
      patients with VTE (P < 0.001).

PMID- 21192760
TI  - A clinical and economic evaluation of enteral nutrition.
AB  - MOTIVATION: The American Society of Parenteral and Enteral Nutrition (ASPEN)
      guidelines advise use of enteral nutrition (EN) for critically ill hospital
      patients requiring nutritional support, but no studies have comprehensively
      estimated economic benefits from adherence to this recommendation. METHODS: We
      systematically reviewed studies comparing EN to alternative nutritional support
      therapies among adult, critically ill patients. We reviewed 1200 abstracts,
      selected 243 for further review, and included 48 studies in our analysis. Most
      retained studies compared EN and parenteral nutrition (PN). Using meta-analysis,
      we estimated the absolute impact of EN on adverse event risk and its impact on
      treatment duration and length of stay. These estimates were converted to
      population economic impacts by assuming 10% of PN patients are suitable
      candidates for EN. RESULTS: Compared to PN, EN reduces the risk of major,
      potentially life-threatening infections (RR = 0.58, 95% confidence interval [CI]
      0.44 to 0.77), the risk of major, potentially life-threatening non-infection
      events (RR = 0.73, CI 0.59 to 0.91), and suggests a reduction in mortality,
      although this result did not achieve statistical significance (RR = 0.70, CI 0.45
      to 1.09). EN also reduces inpatient length of stay, time in the ICU, and length
      of nutritional treatment. Compared to PN, EN savings from reduced adverse event
      risks average nearly $1500 per patient; savings from reduced hospital length of
      stay amount to nearly $2500 per patient. Shifting 10% of parenterally treated
      adult patients in the U.S. to EN would save $35 million annually due to reduced
      adverse events and another $57 million due to shorter hospital stays. CONCLUSION:
      The evidence of both clinical and economic gains from EN is consistent with ASPEN
      guidelines recommending use of EN in critically ill hospital patients when
      possible.

PMID- 21192761
TI  - Respiratory outcomes, utilization and costs 12 months following a respiratory
      syncytial virus diagnosis among commercially insured late-preterm infants.
AB  - OBJECTIVES: To determine, among a commercially-insured population of late-preterm
      infants, utilization of healthcare resources and costs during the 1 year
      following a diagnosis of respiratory syncytial virus lower respiratory infection
      (RSV LRI). METHODS: Administrative claims for non-capitated, commercially-insured
      infants <1 year old were used to identify infants diagnosed with RSV LRI and
      unspecified bronchiolitis/pneumonia (UBP). Infants were stratified by the setting
      of diagnosis. Infants without evidence of RSV LRI or UBP were selected as a
      comparison group. Economic and clinical outcomes were analyzed descriptively
      using propensity score weighting and logged ordinary least squares models were
      used to examine the relationship between RSV and costs (adjusted to 2006 USD)
      incurred within 1 year of RSV LRI. RESULTS: The majority of infants were 3 months
      or older at the time of RSV LRI or UBP diagnosis. The rate of wheezing was
      significantly greater for infants in the RSV LRI and UBP cohorts relative to the
      comparison group (p < 0.001). Infantile asthma rates were 6-9 times higher among
      RSV LRI and UBP infants than the comparison group. RSV LRI and UBP infants also
      had significantly more emergency department visits and outpatient visits than the
      comparison group. The marginal healthcare costs were significantly higher for RSV
      LRI inpatients ($24,027) and outpatients ($2703) infants than for the comparison
      group (all p < 0.001). CONCLUSION: Commercially insured late-preterm infants with
      RSV infection are at high risk for recurrent wheezing and infantile asthma during
      the 1-year period after the initial episode and impose a significant economic
      burden to the healthcare system.

PMID- 21192763
TI  - Auction fever: exploring informational social influences on bidder choices.
AB  - Previous investigations of herd behavior have identified the importance of
      informational social influences in consumer decision making. This research
      presents three studies examining herd behavior in online auctions. The three
      studies addressed the influence on bidder online choices of herd cues frequently
      found in online auctions, including bid number, feedback ratings, and number of
      questions and answers. This research also investigated the effect of different
      levels of herd cues on bidder online choices under high and low brand awareness
      in online auctions. The experimental results demonstrated that bidders use online
      herd cues when making decisions in online auctions. Additionally, different
      levels of herd cues influence bidder online choices in both high and low brand
      awareness product situations.

PMID- 21192764
TI  - Understanding antecedents of continuance intention in social-networking services.
AB  - Given the extreme advances and large investments in social-networking services
      (SNS), it has become important to analyze users' decision-making processes in
      order to understand their continued use of SNS. This study attempted to develop
      an integrated model that incorporates subjective norm into the expectation
      confirmation model. The research model was empirically tested within the context
      of Cyworld. The analysis revealed that the proposed theoretical model provided an
      in-depth understanding of user continuance behavior toward SNS. Theoretical and
      practical implications of this study are discussed.

PMID- 21192765
TI  - The relationship between Facebook and the well-being of undergraduate college
      students.
AB  - We investigated how Facebook use and attitudes relate to self-esteem and college
      adjustment, and expected to find a positive relationship between Facebook and
      social adjustment, and a negative relationship between Facebook, self-esteem, and
      emotional adjustment. We examined these relationships in first-year and upper
      class students and expected to find differences between the groups. Seventy
      undergraduate students completed Facebook measures (time, number of friends,
      emotional and social connection to Facebook), the Rosenberg Self-Esteem Scale,
      and the Student Adaptation to College Scale. First-year students had a stronger
      emotional connection to and spent more time on Facebook while they reported fewer
      friends than upper-class students did. The groups did not differ in the
      adjustment scores. The number of Facebook friends potentially hinders academic
      adjustment, and spending a lot of time on Facebook is related to low self-esteem.
      The number of Facebook friends was negatively associated with emotional and
      academic adjustment among first-year students but positively related to social
      adjustment and attachment to institution among upper-class students. The results
      suggest that the relationship becomes positive later in college life when
      students use Facebook effectively to connect socially with their peers. Lastly,
      the number of Facebook friends and not the time spent on Facebook predicted
      college adjustment, suggesting the value of studying further the notion of
      Facebook friends.

PMID- 21192766
TI  - Morphological and functional changes in multifocal vitelliform retinopathy and
      biallelic mutations in BEST1.
AB  - PURPOSE: To describe morphological and functional changes in a single patient
      with multifocal Best vitelliform macular dystrophy (BVMD) and to perform a
      genotype/phenotype correlation. METHODS: The proband with multifocal BVMD and
      three of her family members were examined with electrooculography (EOG), full
      field electroretinography (full-field ERG), multifocal electroretinography
      (mfERG) and optical coherence tomography (OCT). Genomic DNA was screened for
      mutation in the BEST1 gene by DNA sequencing analysis. RESULTS: The proband was
      observed regularly during a follow-up period of 4 years. Full-field ERG
      demonstrated reduced and delayed responses of both rods and cones. OCT
      demonstrated intra- and subretinal fluid which seemed to fluctuate with periods
      of stress, similar to that seen in chronic central serous chorioretinopathy. Two
      distinct heterozygous BEST1 mutations were identified in the proband, the
      recurrent p.R141H mutation and the p.P233A mutation. Heterozygous p.R141H
      mutations were also identified in two family members, while p.P233A was a de novo
      mutation. Abnormal EOG findings were observed in both the proband and in the
      carriers of p.R141H. Heterozygous carriers showed delayed implicit times in a-
      and b-waves of combined total rod and cone full-field ERG responses. CONCLUSIONS:
      The p.R141H mutation is frequently seen together with multifocal vitelliform
      retinopathy and biallelic mutations in BEST1. Our results show that carriers of
      the p.R141H mutation are clinically unaffected but present with abnormal EOG and
      full-field ERG findings. A patient with biallelic mutations of the BEST1 gene,
      causing multifocal BVMD with progressive, widespread functional disturbance of
      the retina, confirmed by full-field and mfERG is described.

PMID- 21192767
TI  - Using physician-led automated communications to improve patient health.
AB  - One common thread to health care reform in the United States is an emphasis on
      effectively managing the care of patients with chronic conditions. A landmark
      study by McGlynn et al demonstrated that patients receive about 55% of the
      treatment they need. While technological advances allow automated means for
      identifying and reaching out to patients in need of treatment, few studies have
      evaluated their impact. The purpose of this study is to measure how an automated
      outreach program can be used to improve the quality of care for patients with
      diabetes and hypertension. Billing and electronic medical records data from a
      large health system in Wisconsin were studied, identifying patients with a
      history of diabetes and hypertension but no visits recorded in billing data
      related to their condition in the past 6 months. The outcomes of interest were
      the occurrence of a chronic care-related visit and a necessary test within 6
      months of the nonadherence date. Diabetes patients who were successfully
      contacted were significantly more likely to have both a chronic care-related
      visit and an HbA1c test (odds ratio [OR] = 4.61, 95% confidence interval [CI]
      3.87-5.49) than their counterparts who were not contacted. As well, hypertension
      patients were significantly more likely to have both a chronic care-related visit
      and a systolic blood pressure reading recorded in an electronic medical record
      (OR = 3.18, 95% CI 2.90-3.48). An automated patient identification and outreach
      program can be an effective means to supplement existing practice patterns to
      ensure that patients with chronic conditions in need of care receive the
      necessary treatment.

PMID- 21192768
TI  - Awareness and implementation of the 2000 United States public health service
      tobacco dependence treatment guideline in a public hospital system.
AB  - The 2000 United States Public Health Service (USPHS) clinical practice guideline,
      "Treating Tobacco Use and Dependence," recommends systems interventions to
      integrate the treatment of tobacco into routine health care. The Tobacco Control
      Initiative employed a systems approach to integrate evidence-based treatment for
      tobacco use into patient care practices in Louisiana's safety net health care
      system. The purpose of this study was to assess changes in awareness and
      implementation of the USPHS clinical practice guideline. Surveys were
      administered to a purposive sample of hospital personnel from key departments in
      the Louisiana State University system of public hospitals in 2003 (n = 24) and
      2007 (n = 44). Perceptions of implementation success improved for 50 of 59
      distinct survey items. Rasch scaling was used to assess overall (scaled) change
      and showed substantial improvement from 2003 to 2007 (P < 0.001). Survey items
      also were grouped into 6 logical key concept sets. Improvement occurred in
      perceptions for all 6 key concepts; however, not uniformly. Results of the 2003
      and 2007 surveys illustrate the potential effectiveness of using a systems
      approach to integrate the assessment and treatment of tobacco use into routine
      care practices in a public health care delivery system that serves medically
      vulnerable populations.

PMID- 21192769
TI  - The cost effectiveness of rapid-acting insulin aspart compared with human insulin
      in type 2 diabetes patients: an analysis from the Japanese third-party payer
      perspective.
AB  - OBJECTIVES: The Nippon Ultra-Rapid Insulin and Diabetic Complication Evaluation
      Study (NICE Study) (NCT00575172) was a 5-year, open-label, randomised controlled
      trial which compared cardiovascular outcomes in Japanese type 2 diabetes patients
      intensively treated with regular human insulin or insulin aspart (NovoRapid; Novo
      Nordisk A/S, Bagsvaerd, Denmark), a rapid-acting insulin analogue. The aim of the
      present analysis was to evaluate the cost effectiveness of insulin aspart versus
      regular human insulin from the perspective of a Japanese third-party healthcare
      payer. RESEARCH DESIGN AND METHODS: A discrete event-simulation model was
      developed in Microsoft Excel to assess the within-trial cost effectiveness and
      make longer-term clinical projections in patients treated with regular human
      insulin or insulin aspart. In addition to severe hypoglycaemia, the model
      captured myocardial and cerebral infarction events and percutaneous coronary
      intervention and coronary artery bypass graft procedures. Within-trial mortality,
      incidence of severe hypoglycaemia and cardiovascular event probabilities were
      derived from the annual rates observed during the trial period, while post-trial
      outcomes were calculated using the event rates from the trial, adjusted for
      increasing patient age. Event costs were accounted from the healthcare payer
      perspective and expressed in 2008 Japanese yen (JPY), while health-related
      quality of life (HRQoL) was captured using event and state utilities. Future
      costs and clinical benefits were discounted at 3% annually. Life expectancy,
      quality-adjusted life expectancy, cardiovascular event rates and costs were
      evaluated over 5- and 10-year time horizons and sensitivity analyses were
      performed to assess variability in model outcomes. RESULTS: Over 5 years of
      treatment, insulin aspart dominated human insulin both in incremental life
      expectancy and in incremental quality-adjusted life-years (QALYS). Insulin aspart
      was associated with a small improvement in discounted life expectancy of 0.005
      years (4.688 vs. 4.684 years) and an increase of 0.023 quality-adjusted life
      years (QALYs) (3.800 vs. 3.776 QALYs) when compared with regular human insulin.
      Insulin aspart also incurred lower costs (JPY 481,586 vs. 594,717, difference 
      113,131) which resulted from the decreased incidence of cardiovascular events
      with insulin aspart (0.013 events per patient year vs. 0.030 on regular human
      insulin). Breakdown of costs indicated that pharmacy costs were higher with
      insulin aspart (JPY 346,608 vs. 278,468), but these costs were more than offset
      by the reduced costs associated with cardiovascular complications and
      hypoglycaemia over 5 years of treatment (JPY 134,978 vs. 316,249). Sensitivity
      analysis showed that insulin aspart was still cost-effective in the case where
      only 18% of the within-trial cardiovascular and mortality benefit over regular
      human insulin was captured in the model (assuming a willingness-to-pay threshold
      of JPY 5,000,000). LIMITATIONS: The NICE study cohort was relatively small (n =
      325), meaning that caution should be exercised when calculating and interpreting
      the incremental cost-effectiveness ratio. Also, despite the differences in
      cardiovascular risk profile between the Japanese and UK populations, UKPDS
      derived risk equations were used to project MI outcomes and PCI and CABG
      procedures and UKPDS HRQoL scores were applied to all health states. While these
      risk formulas and HRQoL utilities may not be directly applicable to the Japanese
      population, no equivalent Japanese-specific data are currently available.
      CONCLUSIONS: In a Japanese type 2 diabetes population, prescribing rapid-acting
      insulin aspart significantly reduced cardiovascular complications over 5- and 10
      year time horizons, resulting in increased quality of life and decreased costs
      when compared with human insulin.

PMID- 21192770
TI  - Pharmacokinetic evaluation of mycophenolate mofetil for pemphigus.
AB  - INTRODUCTION: Pemphigus is an autoimmune blistering disease of the skin and
      mucous membranes characterized by the development of autoantibodies against the
      desmosomal proteins, desmoglein-1 and -3. Before the advent of corticosteroids,
      therapy was almost fatal. The introduction of high-dose corticosteroid therapy
      has reduced mortality rates to ~ 10%, but long-term use of steroids can lead to
      side effects, many of which are severe and associated with significant morbidity.
      Thus, the major goal of pemphigus therapy has been to reduce the patient's
      cumulative exposure to systemic corticosteroids. Over the last 2 decades, a range
      of corticosteroid-sparing immunosuppressive agents have been described, but these
      therapies are not without potentially serious complications. Despite the range of
      treatment options, a proportion of patients do not achieve remission, while
      others show an initial treatment response but remain poorly controlled. The
      recent availability of mycophenolate mofetil (MMF), originally developed for
      preventing allograft rejection, appears to be effective in autoimmune blistering
      diseases in combination with systemic corticosteroid or as a monotherapy. AREAS
      COVERED: This review aims to provide an extensive overview of the literature on
      the clinical pharmacokinetics of MMF in pemphigus treatment and a brief summary
      of current pharmacodynamic information. After completing this learning activity,
      readers should be able to summarize the pharmacology of MMF as an
      immunosuppressant; recognize its potential role in the treatment of pemphigus,
      including general dosing guidelines and laboratory monitoring schedules, use in
      patient populations and potential adverse effects; and identify future
      considerations and developing areas of research regarding the use of mycophenolic
      acid in the treatment of autoimmune blistering diseases. EXPERT OPINION: Current
      morbidity of pemphigus is largely iatrogenic, caused by side effects of the long
      term, high-dose corticosteroid therapy that is necessary to sustain disease
      control. MMF demonstrates complex pharmacokinetics and displays large between
      subject pharmacokinetic variability. Experience with MMF has demonstrated long
      term safety and tolerability in the treatment of pemphigus.

PMID- 21192771
TI  - The role of circadian timing system on drug metabolism and detoxification.
AB  - INTRODUCTION: It has been known for a long time that the efficiency and toxicity
      of drugs change during a 24-h period. However, the molecular mechanisms involved
      in these processes have started to emerge only recently. AREAS COVERED: This
      review aims to highlight recent discoveries showing the direct role of the
      molecular circadian clock in xenobiotic metabolism at the transcriptional and
      post-transcriptional levels in the liver and intestine, and the different ways of
      elimination of these metabolized drugs via biliary and urine excretions. Most of
      the related literature focuses on transcriptional regulation by the circadian
      clock of xenobiotic metabolism in the liver; however, the role of this timing
      system in the excretion of metabolized drugs and the importance of the kidney in
      this phenomenon are generally neglected. The goal of this review is to describe
      the molecular mechanisms involved in rhythmic drug metabolism and excretion.
      EXPERT OPINION: Chronopharmacology is used to analyze the metabolism of drugs in
      mammals according to the time of day. The circadian timing system plays a key
      role in the changes of toxicity of drugs by influencing their metabolisms in the
      liver and intestine in addition to their excretion via bile flow and urine.

PMID- 21192772
TI  - Sex differences in pharmacokinetics of antidepressants.
AB  - INTRODUCTION: Sex differences have been identified in antidepressant treatment;
      however, it remains unclear to what extent pharmacokinetics contributes to these
      differences. As current antidepressant pharmacotherapy is less than optimal,
      understanding the role of sex in pharmacokinetics may substantially contribute to
      a gender-based optimized treatment. AREAS COVERED: An unrestricted PubMed
      literature search on antidepressant pharmacokinetics and sex was performed. Sex
      differences in absorption, distribution, metabolism and elimination of
      antidepressants, as well as the interaction of sex with age, genetic
      polymorphisms and gonadal hormones are discussed. We also provide an overview of
      how each antidepressant presents a particular sex-differentiated pharmacokinetic
      profile. Most antidepressants present to some extent pharmacokinetic sex
      differences, which often are further accentuated by gonadal hormones. In most
      cases, women, particularly elderly women, are expected to have higher exposure to
      antidepressants when dosed in a similar way as men. EXPERT OPINION: Although the
      available pharmacokinetic evidence indicates that women should receive lower
      doses of antidepressants and men should receive higher doses, current guidelines
      do not recommend dose adjustment, because these sex differences are considered to
      be clinically insignificant. Unless we understand the link between
      pharmacokinetics and pharmacodynamics of antidepressants, it will be difficult to
      determine whether sex differences are of clinical importance or not. Thus,
      further systematic and particularly focused research is needed on sex differences
      in pharmacokinetics.

PMID- 21192773
TI  - Vorinostat in acute myeloid leukemia and myelodysplastic syndromes.
AB  - INTRODUCTION: the results of conventional treatment for acute myeloid leukemia
      (AML) and myelodysplastic syndromes (MDS) remain poor and innovative strategies
      are warranted. With this aim, epigenetic modulation became a promising approach
      over the last years. Vorinostat is an epigenetic targeted drug belonging to the
      histone deacetylase (HDAC) inhibitors family. It is the second-generation HDAC
      inhibitor that has been more extensively studied in AML and MDS. AREAS COVERED:
      in this review, we will present the rationale for its use in AML and MDS,
      describe the drug pharmacologic properties and review the current data available
      from clinical trials. The data presented here will allow the reader to overview
      the common mechanisms of action of this class of compounds in AML and MDS, as
      well as to better understand the biological specificities of vorinostat, and its
      current and future clinical development in the field. EXPERT OPINION: vorinostat
      has shown an acceptable toxicity profile with mainly gastrointestinal and
      constitutional side effects. Efficacy as a single agent is limited in that group
      of patients, but promising results are currently observed with combinations of
      vorinostat and either conventional chemotherapy or investigational agents,
      including demethylating agents.

PMID- 21192774
TI  - Supervisors' responses to sickness certification for an episode of low back pain:
      employees' personal experiences.
AB  - PURPOSE: To understand how work supervisors respond to sickness certification for
      an episode of low back pain based on employees' reports of employer-employee
      interactions. METHOD: Thematic analysis of semi-structured in-depth interviews
      with 16 employees who were currently or had recently been off work with an
      episode of low back pain. RESULTS: Two types of initial supervisor response were
      identified: See you later and take your time and get it right. Both of these
      relied on the employee returning to work once they were able to do their normal
      work tasks. Three types of subsequent response were identified: proactive,
      apathetic and negative. Only the proactive response included actions to encourage
      and assist the employee to return to the workplace. CONCLUSIONS: The interactions
      described by participants suggest that employers and their representatives often
      postpone actioning to return to work interventions which potentially delays the
      rehabilitation of the employee.

PMID- 21192775
TI  - Comparing the priorities of parents and young people with cerebral palsy.
AB  - PURPOSE: Adolescence is a period of change and transition that may pose unique
      challenges for young people with cerebral palsy (CP). We compared statements of
      priorities, i.e. what adolescents (13-17) and youth (18-21) and their parents
      would like to be able to do to enable greater activity and participation.
      METHODS: Participants were 198 parents and 135 young people with CP (45% males)
      from seven Children's Hospitals in the United States. The interviews were
      structured using The Canadian Occupational Performance Measure. Priority
      statements were categorised as Adult Tasks, Biology, Self-Identity or Physical
      Activity. RESULTS: All parents identified more priorities for Biology and Adult
      Tasks (p  <  0.001). Adolescents identified the fewest priorities for Self
      Identity (p  <  0.01). Youth identified, in descending order of frequency,
      priorities in Adult Tasks, Biology, Self-Identity and Physical Activity (p  < 
      0.05). In the parent-young people dyads when disagreements occurred, Self
      Identity issues were identified more often by parents (p  <  0.05) and priorities
      for Physical Activity were identified more often by young people (p  <  0.01).
      CONCLUSIONS: The shared and differing priorities of parents and young people with
      CP may reflect different roles, perceptions and experiences. The findings have
      implications for healthcare professionals, providing a framework to compare and
      contrast the priorities of young people and their parents.

PMID- 21192776
TI  - Antileishmanial patents antileishmanial current drugs and relevant patents.
AB  - The World Health Organization has classified the leishmaniasis as a major
      tropical disease. An effective vaccine is not available and the chemotherapy is
      the only effective way to treat all forms of disease. Currently, the therapy is
      toxic, expensive and the resistance has emerged as a serious problem, which has
      compelled the search for new antileishmanial agents. The aim of this article is
      to review the recent advances in antileishmanial drugs. In addition, patents from
      01/1969 to 12/2009 were analyzed. After initial review, 867 patents were
      classified as vaccines, immunomodulators and drugs. Among them, the major percent
      was reached by the drugs, accounting for 68% of the patents. In this review, 580
      patents were listed, reviewed and classified according the approach of the
      inventors in the expansion of antileishmanial drug discovery. In this moment, the
      scenario of leishmaniasis chemotherapy is more promising than ever. Nevertheless,
      advances in the understanding of new metabolic pathways and drug targets in the
      parasite could offer new alternatives to treatment of leishmaniasis.

PMID- 21192777
TI  - Role and impact of carbapenem in nosocomial infections.
AB  - Although carbapenem antibiotics are one of the most effective agents in the
      treatment of nosocomial infections caused by Gram-negative bacteria, their use is
      threatened by the emergence of antibiotic resistance. The bacterial resistance to
      carbapenems parallels their increasing use and has dramatic clinical implications
      such as increase in mortality and cost of care. This article reviews recently
      published patents claiming for carbapenem antibacterial agents. New forms
      including crystalline forms with high oral bioavailability and modified spectrum
      including methicillin-resistant Staphylococci are some of new patents described
      in this review.

PMID- 21192778
TI  - Heat shock protein inhibitors for the treatment of fungal infections.
AB  - Invasive fungal infections are a leading cause of mortality, especially in
      immunocompromised patients. Therapy is made difficult by the limited number of
      antifungal agents currently available which mostly target ergosterol in fungal
      cell membranes. The paucity of targets allows the development of cross resistance
      to all drugs with a common target. This highlights the need to develop new
      therapeutic strategies for fungal disease including agents with novel mechanisms
      of action. Heat shock protein 90 stabilizes calcineurin which regulates response
      to stress, allowing for calcineurin dependent stress responses required to
      survive exposure to antifungal drugs. Heat shock protein 90 inhibition abrogates
      calcineurin dependent stress responses, changing fungistatic drugs to fungicidal.
      Targeting a highly conserved protein that has a vital role in many cellular
      signaling pathways, reduces the potential for emergence of resistance to heat
      shock proteins inhibitors. This article will review recent patents in novel heat
      shock protein inhibitor therapy, such as efungumab, which diminish the emergence
      of antifungal drug resistance and enable greater efficacy of existing
      antifungals.

PMID- 21192779
TI  - Resistant TB: Newer Drugs and Community Approach.
AB  - Drug resistance in tuberculosis (TB) is a serious problem compromising both the
      treatment and control programs. Poor usage of the available anti TB drugs has led
      to progressive drug resistance-multi drug resistance (MDR), extensively drug
      resistance (XDR) and even total drug resistance (TDR). While drug sensitive TB is
      completely curable, MDR-TB is difficult to treat, XDR and TDR are often fatal.
      Non availability of new drugs to treat drug resistant cases further complicates
      the problem. The Global Alliance for Tuberculosis Drug Developments, a non-profit
      organization with the World Health Organization (WHO) as a partner was formed in
      February 2000 for the development of new drugs. In the last decade this venture
      has resulted in several promising new antituberculosis drugs like TMC207
      (diaryquinoline), PA-824 (nitroimidazo-oxazine), OPC-67683 (nitroimidazo-oxazole)
      and SQ 109 (diamine compound). Drug resistance in TB is a man made problem.
      Therefore, while global efforts towards new drug development must continue it is
      equally important to have a well defined community approach to prevent the
      emergence of drug resistance to the existing and newer drugs. The present review
      article discusses some recent drug patents for the treatment of tuberculosis and
      the appropriate community approach to prevent and treat drug resistant TB.

PMID- 21192781
TI  - The medicinal chemistry of novel iron chelators for the treatment of cancer.
AB  - Cancer is one of the leading causes of death worldwide and there is an increasing
      need for novel anti-tumor therapeutics with greater selectivity and potency. A
      new strategy in the treatment of cancer has focused on targeting an essential
      cell metabolite, iron (Fe). Iron is vital for cell growth and metabolism, forming
      a crucial component of the active site of ribonucleotide reductase (RR), the rate
      limiting enzyme in DNA synthesis. Cancer cells in particular require large
      amounts of Fe to proliferate, making them more susceptible to the Fe deficiency
      caused by Fe chelators. Beginning with primordial siderophores, Fe chelators have
      since evolved to a new generation of potent and efficient anti-cancer agents.
      Recently, investigations have led to the generation of novel di-2-pyridylketone
      thiosemicarbazone (DpT) and 2-benzoylpyridine thiosemicarbazone (BpT) ligands
      that demonstrate marked and selective anti-tumor activity both in vitro and in
      vivo against a wide spectrum of tumors. The mechanism of action of these novel
      ligands includes alterations in the expression of key regulatory molecules as
      well as the generation of redox active Fe complexes. Interestingly, non-synthetic
      Fe chelators including silybin and curcumin, both of which are derived from
      plants, also have vast potential in the treatment of cancer. This review explores
      the development of novel Fe chelators for the treatment of cancer and their
      mechanisms of action.

PMID- 21192782
TI  - Primary syphilis cases in Guangdong Province 1995-2008: opportunities for linking
      syphilis control and regional development.
AB  - BACKGROUND: Syphilis cases have risen in many parts of China, with developed
      regions reporting the greatest share of cases. Since syphilis increases in these
      areas are likely driven by both increased screening and changes in sexual
      behaviours, distinguishing between these two factors is important. Examining
      municipal-level primary syphilis cases with spatial analysis allows a more direct
      understanding of changing sexual behaviours at a more policy-relevant level.
      METHODS: In this study we examined all reported primary syphilis cases from
      Guangdong Province, a southern province in China, since the disease was first
      incorporated into the mandatory reporting system in 1995. Spatial autocorrelation
      statistics were used to correlate municipal-level clustering of reported primary
      syphilis cases and gross domestic product (GDP). RESULTS: A total of 52,036
      primary syphilis cases were reported over the period 1995-2008, and the primary
      syphilis cases increased from 0.88 per 100,000 population in 1995 to 7.61 per
      100,000 in 2008. The Pearl River Delta region has a disproportionate share
      (44.7%) of syphilis cases compared to other regions. Syphilis cases were
      spatially clustered (p = 0.01) and Moran's I analysis found that syphilis cases
      were clustered in municipalities with higher GDP (p = 0.004). CONCLUSIONS:
      Primary syphilis cases continue to increase in Guangdong Province, especially in
      the Pearl River Delta region. Considering the economic impact of syphilis and its
      tendency to spatially cluster, expanded syphilis testing in specific
      municipalities and further investigating the costs and benefits of syphilis
      screening are critical next steps.

PMID- 21192783
TI  - Chicken cyclophilin A is an inhibitory factor to influenza virus replication.
AB  - BACKGROUND: The importance of enhancing influenza resistance in domestic flocks
      is quite clear both scientifically and economically. Chicken is very susceptible
      to influenza virus. It has been reported that human cellular cyclophilin A (CypA)
      impaired influenza virus infection in 293T cells. Whether chicken CypA (chCypA)
      inhibits influenza virus replication is not known. The molecular mechanism of
      resistance in chicken to influenza virus remains to be studied. RESULTS: The
      chCypA gene was isolated and characterized in the present study. It contained an
      ORF of 498 bp encoding a polypeptide of 165 amino acids with an estimated
      molecular mass of 17.8 kDa sharing high identity with mammalian CypA genes. The
      chCypA demonstrated an anti-influenza activity as expected. ChCypA protein was
      shown to be able to specifically interact with influenza virus M1 protein. Cell
      susceptibility to influenza virus was reduced by over-expression of chCypA in CEF
      cells. The production of recombinant influenza virus A/WSN/33 reduced to one
      third in chCypA expressing cells comparing to chCypA absent cells. ChCypA was
      widely distributed in a variety of chicken tissues. It localized in cytoplasm of
      chicken embryo fibroblast (CEF) cells. Avian influenza virus infection induced
      its translocation from cytoplasm into nucleus. ChCypA expression was not
      significantly up-regulated by avian influenza virus infection. The present study
      indicated that chCypA was an inhibitory protein to influenza virus replication,
      suggesting a role as an intrinsic immunity factor against influenza virus
      infection. CONCLUSION: The present data demonstrates that chCypA possesses anti
      influenza virus activity which allows the consideration of genetic improvement
      for resistance to influenza virus in chickens.

PMID- 21192784
TI  - A cross-sectional study of the nutritional status of community-dwelling people
      with idiopathic Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) patients have an increased risk of under
      nutrition, but we are unaware of any population based prevalence studies of under
      nutrition in PD. The main objective of this study was to identify the prevalence,
      and nature, of under-nutrition in a representative population of people with PD.
      METHODS: People diagnosed with idiopathic PD from within two PD prevalence study
      sites in North-East England were asked to participate in this study. Those who
      participated (n = 136) were assessed using a number of standard rating scales
      including Hoehn & Yahr stage and Unified Parkinson's Disease Rating Scale
      (UPDRS). Body mass index (BMI), mid-arm circumference (MAC), triceps skin fold
      thickness (TSF) and grip strength were recorded together with social and
      demographic information. RESULTS: BMI < 20 identified over 15% of the study group
      to have under-nutrition. The Malnutritional Universal Screening Tool (MUST)
      scoring system identified 23.5% of participants at medium or high risk of
      malnutrition. Low BMI, indicating under-nutrition, was associated with greater
      age and disease duration, lower MAC, TSF, mid-arm muscle circumference (MAMC),
      reduced grip strength and a report of unintentional weight loss. Problems
      increased with increasing age and disease duration and were greater in females.
      CONCLUSIONS: Under-nutrition is a problem for around 15% of community dwelling
      people with PD. All PD patients should be screened for under-nutrition; the MUST
      score is a useful early screening tool.

PMID- 21192785
TI  - Gestational trophoblastic neoplasia with retroperitoneal metastases: a fatal
      complication.
AB  - BACKGROUND: Gestational Trophoblastic Neoplasia (GTN) is a pathologic entity that
      can affect any pregnancy and develop long after the termination of the pregnancy.
      Its course can be complicated by metastases to distant sites such as the lung,
      brain, liver, kidney and vagina. The therapeutic approach of this condition
      includes both surgical intervention and chemotherapy. The prognosis depends on
      many prognostic factors that determine the stage of the disease. CASE REPORT: We
      present a woman with GTN and retroperitoneal metastatic disease who came to our
      department and was diagnosed as having high risk metastatic GTN. Accordingly she
      received chemotherapy as primary treatment but unfortunately developed massive
      bleeding after the first course of chemotherapy, was operated in an attempt to
      control bleeding but finally succumbed. CONCLUSION: This case demonstrates that
      GTN, while usually curable, can be a deadly disease requiring improved
      diagnostic, treatment modalities and chemotherapeutic agents. The gynaecologist
      should be aware of all possible metastatic sites of GTN and the patient
      immediately referred to a specialist center for further assessment and treatment.

PMID- 21192787
TI  - Where does public funding for HIV prevention go to? The case of condoms versus
      microbicides and vaccines.
AB  - This study analyses the priorities of public donors in funding HIV prevention by
      either integrated condom programming or HIV preventive microbicides and vaccines
      in the period between 2000 and 2008. It further compares the public funding
      investments of the USA government and European governments, including the EU, as
      we expect the two groups to invest differently in HIV prevention options, because
      their policies on sexual and reproductive health and rights are different. We use
      two existing officially UN endorsed databases to compare the public donor funding
      streams for HIV prevention of these two distinct contributors. In the period 2000
      2008, the relative share of public funding for integrated condom programming
      dropped significantly, while that for research on vaccines and microbicides
      increased. The European public donors gave a larger share to condom programming
      than the United States, but exhibited a similar downward trend in favour of
      funding research on vaccines and microbicides. Both public donor parties invested
      progressively more in research on vaccines and microbicides rather than
      addressing the shortage of condoms and improving access to integrated condom
      programming in developing countries.

PMID- 21192786
TI  - The complete genome sequence of Corynebacterium pseudotuberculosis FRC41 isolated
      from a 12-year-old girl with necrotizing lymphadenitis reveals insights into gene
      regulatory networks contributing to virulence.
AB  - BACKGROUND: Corynebacterium pseudotuberculosis is generally regarded as an
      important animal pathogen that rarely infects humans. Clinical strains are
      occasionally recovered from human cases of lymphadenitis, such as C.
      pseudotuberculosis FRC41 that was isolated from the inguinal lymph node of a 12
      year-old girl with necrotizing lymphadenitis. To detect potential virulence
      factors and corresponding gene-regulatory networks in this human isolate, the
      genome sequence of C. pseudotuberculosis FCR41 was determined by pyrosequencing
      and functionally annotated. RESULTS: Sequencing and assembly of the C.
      pseudotuberculosis FRC41 genome yielded a circular chromosome with a size of
      2,337,913 bp and a mean G+C content of 52.2%. Specific gene sets associated with
      iron and zinc homeostasis were detected among the 2,110 predicted protein-coding
      regions and integrated into a gene-regulatory network that is linked with both
      the central metabolism and the oxidative stress response of FRC41. Two gene
      clusters encode proteins involved in the sortase-mediated polymerization of
      adhesive pili that can probably mediate the adherence to host tissue to
      facilitate additional ligand-receptor interactions and the delivery of virulence
      factors. The prominent virulence factors phospholipase D (Pld) and
      corynebacterial protease CP40 are encoded in the genome of this human isolate.
      The genome annotation revealed additional serine proteases, neuraminidase H,
      nitric oxide reductase, an invasion-associated protein, and acyl-CoA carboxylase
      subunits involved in mycolic acid biosynthesis as potential virulence factors.
      The cAMP-sensing transcription regulator GlxR plays a key role in controlling the
      expression of several genes contributing to virulence. CONCLUSION: The functional
      data deduced from the genome sequencing and the extended knowledge of virulence
      factors indicate that the human isolate C. pseudotuberculosis FRC41 is equipped
      with a distinct gene set promoting its survival under unfavorable environmental
      conditions encountered in the mammalian host.

PMID- 21192788
TI  - Genome-wide SNP identification by high-throughput sequencing and selective
      mapping allows sequence assembly positioning using a framework genetic linkage
      map.
AB  - BACKGROUND: Determining the position and order of contigs and scaffolds from a
      genome assembly within an organism's genome remains a technical challenge in a
      majority of sequencing projects. In order to exploit contemporary technologies
      for DNA sequencing, we developed a strategy for whole genome single nucleotide
      polymorphism sequencing allowing the positioning of sequence contigs onto a
      linkage map using the bin mapping method. RESULTS: The strategy was tested on a
      draft genome of the fungal pathogen Venturia inaequalis, the causal agent of
      apple scab, and further validated using sequence contigs derived from the diploid
      plant genome Fragaria vesca. Using our novel method we were able to anchor 70%
      and 92% of sequences assemblies for V. inaequalis and F. vesca, respectively, to
      genetic linkage maps. CONCLUSIONS: We demonstrated the utility of this approach
      by accurately determining the bin map positions of the majority of the large
      sequence contigs from each genome sequence and validated our method by mapping
      single sequence repeat markers derived from sequence contigs on a full mapping
      population.

PMID- 21192789
TI  - SPC-P1: a pathogenicity-associated prophage of Salmonella paratyphi C.
AB  - BACKGROUND: Salmonella paratyphi C is one of the few human-adapted pathogens
      along with S. typhi, S. paratyphi A and S. paratyphi B that cause typhoid, but it
      is not clear whether these bacteria cause the disease by the same or different
      pathogenic mechanisms. Notably, these typhoid agents have distinct sets of large
      genomic insertions, which may encode different pathogenicity factors. Previously
      we identified a novel prophage, SPC-P1, in S. paratyphi C RKS4594 and wondered
      whether it might be involved in pathogenicity of the bacteria. RESULTS: We
      analyzed the sequence of SPC-P1 and found that it is an inducible phage with an
      overall G+C content of 47.24%, similar to that of most Salmonella phages such as
      P22 and ST64T but significantly lower than the 52.16% average of the RKS4594
      chromosome. Electron microscopy showed short-tailed phage particles very similar
      to the lambdoid phage CUS-3. To evaluate its roles in pathogenicity, we
      lysogenized S. paratyphi C strain CN13/87, which did not have this prophage, and
      infected mice with the lysogenized CN13/87. Compared to the phage-free wild type
      CN13/87, the lysogenized CN13/87 exhibited significantly increased virulence and
      caused multi-organ damages in mice at considerably lower infection doses.
      CONCLUSIONS: SPC-P1 contributes pathogenicity to S. paratyphi C in animal
      infection models, so it is possible that this prophage is involved in typhoid
      pathogenesis in humans. Genetic and functional analyses of SPC-P1 may facilitate
      the study of pathogenic evolution of the extant typhoid agents, providing
      particular help in elucidating the pathogenic determinants of the typhoid agents.

PMID- 21192790
TI  - Engineering building blocks for self-assembling protein nanoparticles.
AB  - Like natural viruses, manmade protein cages for drug delivery are to be ideally
      formed by repetitive subunits with self-assembling properties, mimicking viral
      functions and molecular organization. Naturally formed nanostructures (such as
      viruses, flagella or simpler protein oligomers) can be engineered to acquire
      specific traits of interest in biomedicine, for instance through the addition of
      cell targeting agents for desired biodistribution and specific delivery of
      associated drugs. However, fully artificial constructs would be highly desirable
      regarding finest tuning and adaptation to precise therapeutic purposes. Although
      engineering of protein assembling is still in its infancy, arising principles and
      promising strategies of protein manipulation point out the rational construction
      of nanoscale protein cages as a feasible concept, reachable through conventional
      recombinant DNA technologies and microbial protein production.

PMID- 21192791
TI  - RFX1 regulates CD70 and CD11a expression in lupus T cells by recruiting the
      histone methyltransferase SUV39H1.
AB  - INTRODUCTION: Regulatory factor X-box 1 (RFX1) can interact with DNA
      methyltransferase 1 (DNMT1) and histone deacetylase 1 (HDAC1), and RFX1 down
      regulation contributes to DNA hypomethylation and histone H3 hyperacetylation at
      the cluster of differentiation (CD) 11a and CD70 promoters in CD4(+) T cells of
      patients with systemic lupus erythematosus (SLE). This leads to CD11a and CD70
      overexpression, thereby triggering autoimmune responses. In order to provide more
      insight into the epigenetic mechanisms leading to the deregulation of autoimmune
      related genes in SLE, we asked whether RFX1 is involved in regulating histone 3
      lysine 9 (H3K9) tri-methylation at the CD11a and CD70 promoters in SLE CD4(+) T
      cells. METHODS: CD4(+) T cell samples were isolated from 15 SLE patients and 15
      healthy controls. H3K9 tri-methylation levels were measured by chromatin
      immunoprecipitation (ChIP) and real-time quantitative PCR. CD4(+) T cells were
      transfected with plasmids using the Human T cell Nucleofector Kit. RFX1 and
      histone methyltransferase suppressor of variegation 3-9 (Drosophila) homolog 1
      (SUV39H1) interaction was determined by co-immunoprecipation (co-IP) and Western
      blot and immunofluorescence staining. CD11a and CD70 mRNA levels were measured by
      real-time RT-PCR. RESULTS: H3K9 tri-methylation levels were significantly reduced
      within the CD11a and CD70 promoter regions in SLE CD4(+) T cells. RFX1 co
      immunoprecipitated with SUV39H1 at the CD11a and CD70 promoters in healthy
      control CD4(+) T cells. Overexpressing or knocking-down RFX1 revealed that RFX1
      expression correlated with H3K9 tri-methylation levels, as well as CD11a and CD70
      expression levels in CD4(+) T cells. CONCLUSIONS: RFX1 recruits SUV39H1 to the
      promoter regions of the CD11a and CD70 genes in CD4(+) T cells, thereby
      regulating local H3K9 tri-methylation levels. These findings shed further light
      on the central role of RFX1 down-regulation in the epigenetic de-repression of
      auto-immune genes in SLE.

PMID- 21192793
TI  - Knowledge of Chlamydia trachomatis among men and women approached to participate
      in community-based screening, Scotland, UK.
AB  - BACKGROUND: Poor awareness and knowledge of Chlamydia trachomatis could be a
      barrier to uptake of screening. This study aimed to determine the level of
      awareness and knowledge of chlamydia among young people who were being approached
      in a variety of community settings and offered opportunistic screening. METHODS:
      Men and women aged 16-24 years were approached in education, health and fitness,
      and workplace settings and invited to complete a self-administered questionnaire
      then provide a urine sample for chlamydia testing. Follow-up semi-structured
      interviews with 24 respondents were carried out after test results were received.
      RESULTS: 363 questionnaires were completed (43.5% from men). Whilst awareness of
      chlamydia was high, knowledge decreased as questions became increasingly focussed
      so that around half of respondents were unaware of the asymptomatic nature of
      chlamydia infections. Men's knowledge of symptoms was consistently lower than
      women's, with most men failing to identify unusual discharge as a symptom in men
      (men 58.3%, female 45.8%, p = 0.019); fewer men knew unusual discharge was a
      symptom among women (men 65.3% female 21.4%, p < 0.001). The asymptomatic nature
      of the infection resonated with respondents and was the commonest piece of
      information they picked up from their participation in the study. CONCLUSIONS:
      Despite scientific gains in understanding chlamydia infection, public
      understanding remains limited. Greater efforts are required to translate
      scientific evidence to the public. An improvement in knowledge may maximise gains
      from interventions to improve detection.

PMID- 21192792
TI  - Preclinical evaluation of KIT/PDGFRA and mTOR inhibitors in gastrointestinal
      stromal tumors using small animal FDG PET.
AB  - BACKGROUND: Primary and secondary drug resistance to imatinib and sunitinib in
      patients with gastrointestinal stromal tumors (GISTs) has led to a pressing need
      for new therapeutic strategies such as drug combinations. Most GISTs are caused
      by mutations in the KIT receptor, leading to upregulated KIT tyrosine kinase
      activity. Imatinib and nilotinib directly inhibit the kinase activity of KIT,
      while RAD001 (everolimus) inhibits mTOR. We report a preclinical study on drug
      combinations in a xenograft model of GIST in which effects on tumor dimensions
      and metabolic activity were assessed by small animal PET imaging. METHODS: Rag2-/
      ; gammacommon -/- male mice were injected s.c. into the right leg with GIST 882.
      The animals were randomized into 6 groups of 6 animals each for different
      treatment regimens: No therapy (control), imatinib (150 mg/kg b.i.d.) by oral
      gavage for 6 days, then once/day for another 7 days, everolimus (10 mg/kg/d.) by
      oral gavage, everolimus (10 mg/kg/d.) + imatinib (150 mg/kg b.i.d.) by oral
      gavage for 6 days, then once/day for another 7 days, nilotinib (75 mg/kg/d.) by
      oral gavage, nilotinib (75 mg/kg/d.) + imatinib (150 mg/kg b.i.d) by oral gavage
      for 6 days, then once/day for another 7 days. Tumor growth control was evaluated
      by measuring tumor volume (cm3). Small animal PET (GE Explore tomography) was
      used to evaluate tumor metabolism and performed in one animal per group at base
      line then after 4 and 13 days of treatment. RESULTS: After a median latency time
      of 31 days, tumors grew in all animals (volume 0,06-0,15 cm3) and the treatments
      began at day 38 after cell injection. Tumor volume control (cm3) after 13 days of
      treatment was > 0.5 for imatinib alone and nilotinib alone, and < 0.5 for the 2
      combinations of drugs and for everolimus alone. The baseline FDG uptake was
      positive in all animals. FDG/SUV/TBR was strongly reduced over time by everolimus
      both as a single agent and in combination with imatinib respectively: 3.1 vs. 2.3
      vs. 1.9 and 2.5 vs 2.3 vs 0. CONCLUSIONS: As single agents, all drugs showed an
      anti-tumor effect in GIST xenografts but everolimus was superior. The everolimus
      plus imatinib combination appeared to be the most active regimen both in terms of
      inhibiting tumor growth and tumor metabolism. The integration of everolimus in
      GIST treatment merits further investigation.

PMID- 21192795
TI  - Perceived barriers and facilitators to mental health help-seeking in young
      people: a systematic review.
AB  - BACKGROUND: Adolescents and young adults frequently experience mental disorders,
      yet tend not to seek help. This systematic review aims to summarise reported
      barriers and facilitators of help-seeking in young people using both qualitative
      research from surveys, focus groups, and interviews and quantitative data from
      published surveys. It extends previous reviews through its systematic research
      methodology and by the inclusion of published studies describing what young
      people themselves perceive are the barriers and facilitators to help-seeking for
      common mental health problems. METHODS: Twenty two published studies of perceived
      barriers or facilitators in adolescents or young adults were identified through
      searches of PubMed, PsycInfo, and the Cochrane database. A thematic analysis was
      undertaken on the results reported in the qualitative literature and quantitative
      literature. RESULTS: Fifteen qualitative and seven quantitative studies were
      identified. Young people perceived stigma and embarrassment, problems recognising
      symptoms (poor mental health literacy), and a preference for self-reliance as the
      most important barriers to help-seeking. Facilitators were comparatively under
      researched. However, there was evidence that young people perceived positive past
      experiences, and social support and encouragement from others as aids to the help
      seeking process. CONCLUSIONS: Strategies for improving help-seeking by
      adolescents and young adults should focus on improving mental health literacy,
      reducing stigma, and taking into account the desire of young people for self
      reliance.

PMID- 21192794
TI  - Early activation of wheat polyamine biosynthesis during Fusarium head blight
      implicates putrescine as an inducer of trichothecene mycotoxin production.
AB  - BACKGROUND: The fungal pathogen Fusarium graminearum causes Fusarium Head Blight
      (FHB) disease on wheat which can lead to trichothecene mycotoxin (e.g.
      deoxynivalenol, DON) contamination of grain, harmful to mammalian health. DON is
      produced at low levels under standard culture conditions when compared to plant
      infection but specific polyamines (e.g. putrescine and agmatine) and amino acids
      (e.g. arginine and ornithine) are potent inducers of DON by F. graminearum in
      axenic culture. Currently, host factors that promote mycotoxin synthesis during
      FHB are unknown, but plant derived polyamines could contribute to DON induction
      in infected heads. However, the temporal and spatial accumulation of polyamines
      and amino acids in relation to that of DON has not been studied. RESULTS:
      Following inoculation of susceptible wheat heads by F. graminearum, DON
      accumulation was detected at two days after inoculation. The accumulation of
      putrescine was detected as early as one day following inoculation while arginine
      and cadaverine were also produced at three and four days post-inoculation.
      Transcripts of ornithine decarboxylase (ODC) and arginine decarboxylase (ADC),
      two key biosynthetic enzymes for putrescine biosynthesis, were also strongly
      induced in heads at two days after inoculation. These results indicated that
      elicitation of the polyamine biosynthetic pathway is an early response to FHB.
      Transcripts for genes encoding enzymes acting upstream in the polyamine
      biosynthetic pathway as well as those of ODC and ADC, and putrescine levels were
      also induced in the rachis, a flower organ supporting DON production and an
      important route for pathogen colonisation during FHB. A survey of 24 wheat
      genotypes with varying responses to FHB showed putrescine induction is a general
      response to inoculation and no correlation was observed between the accumulation
      of putrescine and infection or DON accumulation. CONCLUSIONS: The activation of
      the polyamine biosynthetic pathway and putrescine in infected heads prior to
      detectable DON accumulation is consistent with a model where the pathogen
      exploits the generic host stress response of polyamine synthesis as a cue for
      production of trichothecene mycotoxins during FHB disease. However, it is likely
      that this mechanism is complicated by other factors contributing to resistance
      and susceptibility in diverse wheat genetic backgrounds.

PMID- 21192796
TI  - Pseudomonas aeruginosa beta-lactamase induction requires two permeases, AmpG and
      AmpP.
AB  - BACKGROUND: In Enterobacteriaceae, beta-lactam antibiotic resistance involves
      murein recycling intermediates. Murein recycling is a complex process with
      discrete steps taking place in the periplasm and the cytoplasm. The AmpG permease
      is critical to this process as it transports N-acetylglucosamine anhydrous N
      acetylmuramyl peptides across the inner membrane. In Pseudomonadaceae, this
      intrinsic mechanism remains to be elucidated. Since the mechanism involves two
      cellular compartments, the characterization of transporters is crucial to
      establish the link. RESULTS: Pseudomonas aeruginosa PAO1 has two ampG paralogs,
      PA4218 (ampP) and PA4393 (ampG). Topology analysis using beta-galactosidase and
      alkaline phosphatase fusions indicates ampP and ampG encode proteins which
      possess 10 and 14 transmembrane helices, respectively, that could potentially
      transport substrates. Both ampP and ampG are required for maximum expression of
      beta-lactamase, but complementation and kinetic experiments suggest they act
      independently to play different roles. Mutation of ampG affects resistance to a
      subset of beta-lactam antibiotics. Low-levels of beta-lactamase induction occur
      independently of either ampP or ampG. Both ampG and ampP are the second members
      of two independent two-gene operons. Analysis of the ampG and ampP operon
      expression using beta-galactosidase transcriptional fusions showed that in PAO1,
      ampG operon expression is beta-lactam and ampR-independent, while ampP operon
      expression is beta-lactam and ampR-dependent. beta-lactam-dependent expression of
      the ampP operon and independent expression of the ampG operon is also dependent
      upon ampP. CONCLUSIONS: In P. aeruginosa, beta-lactamase induction occurs in at
      least three ways, induction at low beta-lactam concentrations by an as yet
      uncharacterized pathway, at intermediate concentrations by an ampP and ampG
      dependent pathway, and at high concentrations where although both ampP and ampG
      play a role, ampG may be of greater importance. Both ampP and ampG are required
      for maximum induction. Similar to ampC, ampP expression is inducible in an ampR
      dependent manner. Importantly, ampP expression is autoregulated and ampP also
      regulates expression of ampG. Both AmpG and AmpP have topologies consistent with
      functions in transport. Together, these data suggest that the mechanism of beta
      lactam resistance of P. aeruginosa is distinct from well characterized systems in
      Enterobacteriaceae and involves a highly complicated interaction between these
      putative permeases and known Amp proteins.

PMID- 21192797
TI  - Study protocol: the sleeping sound with attention-deficit/hyperactivity disorder
      project.
AB  - BACKGROUND: Up to 70% of children with Attention-Deficit/Hyperactivity Disorder
      (ADHD) experience sleep problems including difficulties initiating and
      maintaining sleep. Sleep problems in children with ADHD can result in poorer
      child functioning, impacting on school attendance, daily functioning and
      behaviour, as well as parental mental health and work attendance. The Sleeping
      Sound with ADHD trial aims to investigate the efficacy of a behavioural sleep
      program in treating sleep problems experienced by children with ADHD. We have
      demonstrated the feasibility and the acceptability of this treatment program in a
      pilot study. METHODS/DESIGN: This randomised controlled trial (RCT) is being
      conducted with 198 children (aged between 5 to 12 years) with ADHD and moderate
      to severe sleep problems. Children are recruited from public and private
      paediatric practices across the state of Victoria, Australia. Upon receiving
      informed written consent, families are randomised to receive either the
      behavioural sleep intervention or usual care. The intervention consists of two
      individual, face-to-face consultations and a follow-up phone call with a trained
      clinician (trainee consultant paediatrician or psychologist), focusing on the
      assessment and management of child sleep problems. The primary outcome is parent-
      and teacher-reported ADHD symptoms (ADHD Rating Scale IV). Secondary outcomes are
      child sleep (actigraphy and parent report), behaviour, daily functioning, school
      attendance and working memory, as well as parent mental health and work
      attendance. We are also assessing the impact of children's psychiatric
      comorbidity (measured using a structured diagnostic interview) on treatment
      outcome. DISCUSSION: To our knowledge, this is the first RCT of a behavioural
      intervention aiming to treat sleep problems in children with ADHD. If effective,
      this program will provide a feasible non-pharmacological and acceptable
      intervention improving child sleep and ADHD symptoms in this patient group. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN68819261. ISRCTN: ISRCTN68819261.

PMID- 21192798
TI  - Bottom-up driven involuntary attention modulates auditory signal in noise
      processing.
AB  - BACKGROUND: Auditory evoked responses can be modulated by both the sequencing and
      the signal-to-noise ratio of auditory stimuli. Constant sequencing as well as
      intense masking sounds basically lead to N1m response amplitude reduction.
      However, the interaction between these two factors has not been investigated so
      far. Here, we presented subjects tone stimuli of different frequencies, which
      were either concatenated in blocks of constant frequency or in blocks of randomly
      changing frequencies. The tones were presented either in silence or together with
      broad-band noises of varying levels. RESULTS: In silence, tones presented with
      random sequencing elicited a larger N1m response than tones presented with
      constant sequencing. With increasing noise level, this difference decreased and
      even vanished in the condition where noise intensity exceeded the tone intensity
      by 10 dB. Furthermore, under noisy conditions, the N1m latency was shorter in the
      constant sequencing condition compared to the random sequencing condition.
      CONCLUSIONS: Besides the well-known neural habituation mechanisms, bottom-up
      driven attention plays an important role during auditory processing in noisy
      environments. This bottom-up driven attention would allow us to track a certain
      auditory signal in noisy situations without voluntarily paying attention to the
      auditory modality.

PMID- 21192799
TI  - Bayesian estimation of genomic copy number with single nucleotide polymorphism
      genotyping arrays.
AB  - BACKGROUND: The identification of copy number aberration in the human genome is
      an important area in cancer research. We develop a model for determining genomic
      copy numbers using high-density single nucleotide polymorphism genotyping
      microarrays. The method is based on a Bayesian spatial normal mixture model with
      an unknown number of components corresponding to true copy numbers. A reversible
      jump Markov chain Monte Carlo algorithm is used to implement the model and
      perform posterior inference. RESULTS: The performance of the algorithm is
      examined on both simulated and real cancer data, and it is compared with the
      popular CNAG algorithm for copy number detection. CONCLUSIONS: We demonstrate
      that our Bayesian mixture model performs at least as well as the hidden Markov
      model based CNAG algorithm and in certain cases does better. One of the added
      advantages of our method is the flexibility of modeling normal cell contamination
      in tumor samples.

PMID- 21192800
TI  - High serum cortisol level is associated with increased risk of delirium after
      coronary artery bypass graft surgery: a prospective cohort study.
AB  - INTRODUCTION: The pathophysiology of postoperative delirium remains poorly
      understood. The purpose of this study was to examine the relationship between
      serum cortisol level and occurrence of early postoperative delirium in patients
      undergoing coronary artery bypass graft (CABG) surgery. METHODS: A total of 243
      patients undergoing elective CABG surgery were enrolled. Patients were examined
      twice daily during the first five postoperative days and postoperative delirium
      was diagnosed by using the Confusion Assessment Method for the Intensive Care
      Unit (CAM-ICU). Blood samples were obtained between 7 a.m. and 8 a.m. on the
      first postoperative day and serum cortisol concentrations were then measured.
      Multivariate logistic regression analyses were performed to identify risk factors
      of postoperative delirium. RESULTS: Postoperative delirium occurred in 50.6% (123
      of 243) of patients. High serum cortisol level was significantly associated with
      increased risk of postoperative delirium (OR 3.091, 95% CI 1.763-5.418, P <
      0.001). Other independent risk factors of postoperative delirium included
      increasing age (OR 1.111, 95% CI 1.065-1.159, P < 0.001), history of diabetes
      mellitus (OR 1.905, 95% CI 1.001-3.622, P = 0.049), prolonged duration of surgery
      (OR 1.360, 95% CI 1.010-1.831, P = 0.043), and occurrence of complications within
      the first day after surgery (OR 2.485, 95% CI 1.184-5.214, P = 0.016). Patients
      who developed postoperative delirium had a higher incidence of postoperative
      complications and a prolonged duration of postoperative ICU and hospital stay.
      CONCLUSIONS: Delirium was a common complication after CABG surgery. High serum
      cortisol level was associated with increased risk of postoperative delirium.
      Patients who developed delirium had outcomes worse than those who did not.

PMID- 21192801
TI  - Characteristics of martial art injuries in a defined Canadian population: a
      descriptive epidemiological study.
AB  - BACKGROUND: The martial arts have emerged as common activities in the Canadian
      population, yet few studies have investigated the occurrence of associated
      injuries on a population basis. METHODS: We performed such an investigation and
      suggest potential opportunities for prevention. The data source was 14 years
      (1993 to 2006) of records from the Kingston sites of the Canadian Hospital Injury
      Reporting and Prevention Program (CHIRPP). RESULTS: 920 cases were identified.
      Incidence rates were initially estimated using census data as denominators. We
      then imputed annual injury rates per 10000 using a range of published estimates
      of martial arts participation available from a national survey. Rates of injury
      in males and females were 2300 and 1033 per 10000 (0.3% participation) and 575
      and 258 per 10000 (1.2% participation). Injuries were most frequently reported in
      karate (33%) and taekwondo (14%). The most common mechanisms of injury were
      falls, throws and jumps (33%). Fractures (20%) were the most frequently reported
      type of injury and the lower limb was the most common site of injury (41%).
      CONCLUSIONS: Results provide a foundation for potential interventions with a
      focus on falls, the use of weapons, participation in tournaments, as well as head
      and neck trauma.

PMID- 21192802
TI  - Faecal pharmacokinetics of orally administered vancomycin in patients with
      suspected Clostridium difficile infection.
AB  - BACKGROUND: Oral vancomycin (125 mg qid) is recommended as treatment of severe
      Clostridium difficile infection (CDI). Higher doses (250 or 500 mg qid) are
      sometimes recommended for patients with very severe CDI, without supporting
      clinical evidence. We wished to determine to what extent faecal levels of
      vancomycin vary according to diarrhoea severity and dosage, and whether it is
      rational to administer high-dose vancomycin to selected patients. METHODS: We
      recruited hospitalized adults suspected to have CDI for whom oral vancomycin
      (125, 250 or 500 mg qid) had been initiated. Faeces were collected up to 3
      times/day and levels were measured with the AxSYM fluorescence polarization
      immunoassay. RESULTS: Fifteen patients (9 with confirmed CDI) were treated with
      oral vancomycin. Patients with >= 4 stools daily presented lower faecal
      vancomycin levels than those with a lower frequency. Higher doses of oral
      vancomycin (250 mg or 500 mg qid) led to consistently higher faecal levels (>
      2000 mg/L), which were 3 orders of magnitude higher than the MIC90 of vancomycin
      against C. difficile. One patient receiving 125 mg qid had levels below 50 mg/L
      during the first day of treatment. CONCLUSIONS: Faecal levels of vancomycin are
      proportional to the dosage administered and, even in patients with increased
      stool frequency, much higher than the MIC90. Patients given the standard 125 mg
      qid dosage might have low faecal levels during the first day of treatment. A
      loading dose of 250 mg or 500 mg qid during the first 24-48 hours followed by the
      standard dosage should be evaluated in larger studies, since it might be less
      disruptive to the colonic flora and save unnecessary costs.

PMID- 21192803
TI  - Genotypes of human papilloma virus in Sudanese women with cervical pathology.
AB  - BACKGROUND: Knowledge of the distribution of human papillomavirus (HPV) genotypes
      among women with cervical lesion and in invasive cervical cancer is crucial to
      guide the introduction of prophylactic vaccines. There is no published data
      concerning HPV and cervical abnormalities in Sudan. This study aimed to define
      the prevalence of HPV and its subtypes in the cervical smears of women presenting
      with gynecological complains at Omdurman Military Hospital, Sudan.During the
      period between March 2003 and April 2004, 135 cervical smears collected from
      these women, were screened using cytological techniques, and analysed by PCR for
      (beta)-globin and HPV DNA using gel electrophoresis and ELISA. RESULTS: Of these
      135 smears, there were 94 (69.3%) negative, 22 (16.3%) positive for inflammation,
      12(8.9) mild dyskaryosis, 5 (3.7) moderate dyskaryosis and 2 (1.8) severe
      dyskaryosis. There were 60.7% beta. globin positive samples for HPV indicating
      DNA integrity. HPV DNA was identified in three samples (2.2%) by gel
      electrophoresis and. was positive in four samples (2.9%) as single and multiple
      infections by PCR-ELISA. The high risk HPV types 16 and 58 were identified in one
      sample as a mixed infection. The low risk HPV types 40 and 42 were also found as
      a mixed infection in another patient. HPV types 58 and 42 were identified in the
      other two patients. CONCLUSION: HPV type distribution in Sudan appears to differ
      from that in other countries. The HPV genotypes identified were not associated
      with cancer.

PMID- 21192805
TI  - The normal development of Platynereis dumerilii (Nereididae, Annelida).
AB  - BACKGROUND: The polychaete annelid Platynereis dumerilii is an emerging model
      organism for the study of molecular developmental processes, evolution,
      neurobiology and marine biology. Annelids belong to the Lophotrochozoa, the so
      far understudied third major branch of bilaterian animals besides deuterostomes
      and ecdysozoans. P. dumerilii has proven highly relevant to explore ancient
      bilaterian conditions via comparison to the deuterostomes, because it has
      accumulated less evolutionary change than conventional ecdysozoan models.
      Previous staging was mainly referring to hours post fertilization but did not
      allow matching stages between studies performed at (even slightly) different
      temperatures. To overcome this, and to provide a first comprehensive description
      of P. dumerilii normal development, a temperature-independent staging system is
      needed. RESULTS: Platynereis dumerilii normal development is subdivided into 16
      stages, starting with the zygote and ending with the death of the mature worms
      after delivering their gametes. The stages described can be easily identified by
      conventional light microscopy or even by dissecting scope. Developmental
      landmarks such as the beginning of phototaxis, the visibility of the stomodeal
      opening and of the chaetae, the first occurrence of the ciliary bands, the
      formation of the parapodia, the extension of antennae and cirri, the onset of
      feeding and other characteristics are used to define different developmental
      stages. The morphology of all larval stages as well as of juveniles and adults is
      documented by light microscopy. We also provide an overview of important steps in
      the development of the nervous system and of the musculature, using fluorescent
      labeling techniques and confocal laser-scanning microscopy. Timing of each
      developmental stage refers to hours post fertilization at 18 +/- 0.1 degrees C.
      For comparison, we determined the pace of development of larvae raised at 14
      degrees C, 16 degrees C, 20 degrees C, 25 degrees C, 28 degrees C and 30 degrees
      C. A staging ontology representing the comprehensive list of developmental stages
      of P. dumerilii is available online. CONCLUSIONS: Our atlas of Platynereis
      dumerilii normal development represents an important resource for the growing
      Platynereis community and can also be applied to other nereidid annelids.

PMID- 21192804
TI  - Epithelial cell-directed efferocytosis in the post-partum mammary gland is
      necessary for tissue homeostasis and future lactation.
AB  - BACKGROUND: Mammary glands harbor a profound burden of apoptotic cells (ACs)
      during post-lactational involution, but little is known regarding mechanisms by
      which ACs are cleared from the mammary gland, or consequences if this process is
      interrupted. We investigated AC clearance, also termed efferocytosis, during post
      lactational remodeling, using mice deficient for MerTK, Axl, and Tyro3, three
      related receptor tyrosine kinases (RTKs) regulating macrophage-mediated
      efferocytosis in monocytes. MerTK expression, apoptosis and the accumulation of
      apoptotic debris were examined in histological sections of MerTK-deficient,
      Axl/Tyro3-deficient, and wild-type mammary glands harvested at specific time
      points during lactation and synchronized involution. The ability of primary
      mammary epithelial cells (MECs) to engulf ACs was assessed in culture. Transplant
      of MerTK-deficient mammary epithelium into cleared WT mammary fat pads was used
      to assess the contribution of WT mammary macrophages to post-lactational
      efferocytosis. RESULTS: ACs induced MerTK expression in MECs, resulting in
      elevated MerTK levels at the earliest stages of involution. Loss of MerTK
      resulted in AC accumulation in post-lactational MerTK-deficient mammary glands,
      but not in Axl and Tyro3-deficient mammary glands. Increased vascularization,
      fibrosis, and epithelial hyperproliferation were observed in MerTK-deficient
      mammary glands through at least 60 days post-weaning, due to failed efferocytosis
      after lactation, but did not manifest in nulliparous mice. WT host-derived
      macrophages failed to rescue efferocytosis in transplanted MerTK-deficient
      mammary epithelium. CONCLUSION: Efferocytosis by MECs through MerTK is crucial
      for mammary gland homeostasis and function during the post-lactational period.
      Efferocytosis by MECs thus limits pathologic consequences associated with the
      apoptotic load following lactation.

PMID- 21192806
TI  - Children from Baffin Island have a disproportionate burden of tuberculosis in
      Canada: data from the Children's Hospital of Eastern Ontario (1998-2008).
AB  - BACKGROUND: The Children's Hospital of Eastern Ontario (CHEO) provides services
      to children in Baffin Island, through the Baffin Island Pediatric Health
      Initiative. Tuberculosis (TB) remains a major public health problem in that
      region. The objective of our study was to describe the origin and clinical
      characteristics of patients with TB disease at CHEO, since the inception of the
      Baffin Island Pediatric Health Initiative. METHODS: All charts with a discharge
      diagnosis of TB disease during the first 10 years of the Baffin Island program
      were reviewed. Patients meeting a pre-determined case definition were included in
      analyses. A standard medical record abstraction form was used for patient data
      collection. RESULTS: Twenty patients met our case definition. Seven (35%) were
      Canadian-born children from Baffin Island. Seven resided in Ontario, 4 in Quebec,
      and 2 were visiting from other countries. All 7 children residing in Ontario were
      born in African countries. Endothoracic disease occurred in 16 patients (80%),
      including 9 with primary pulmonary TB, and 3 with sputum smear positive "adult
      type" disease. Extrathoracic disease was present in 6 children (30%), including 3
      with CNS disease. Three children had disease in 2 separate sites. CONCLUSIONS:
      While Baffin Island makes up 1% of the hospital catchment population, they
      contributed 35% of TB patients, and the only TB death. While TB in foreign-born
      children is due in part to epidemics abroad, the problem in Baffin Island is a
      reflection of disease burden and transmission within Canada.

PMID- 21192807
TI  - Transcriptome analysis of grain-filling caryopses reveals involvement of multiple
      regulatory pathways in chalky grain formation in rice.
AB  - BACKGROUND: Grain endosperm chalkiness of rice is a varietal characteristic that
      negatively affects not only the appearance and milling properties but also the
      cooking texture and palatability of cooked rice. However, grain chalkiness is a
      complex quantitative genetic trait and the molecular mechanisms underlying its
      formation are poorly understood. RESULTS: A near-isogenic line CSSL50-1 with high
      chalkiness was compared with its normal parental line Asominori for grain
      endosperm chalkiness. Physico-biochemical analyses of ripened grains showed that,
      compared with Asominori, CSSL50-1 contains higher levels of amylose and 8 DP
      (degree of polymerization) short-chain amylopectin, but lower medium length 12 DP
      amylopectin. Transcriptome analysis of 15 DAF (day after flowering) caryopses of
      the isogenic lines identified 623 differential expressed genes (P < 0.01), among
      which 324 genes are up-regulated and 299 down-regulated. These genes were
      classified into 18 major categories, with 65.3% of them belong to six major
      functional groups: signal transduction, cell rescue/defense, transcription,
      protein degradation, carbohydrate metabolism and redox homeostasis. Detailed
      pathway dissection demonstrated that genes involved in sucrose and starch
      synthesis are up-regulated, whereas those involved in non-starch polysaccharides
      are down regulated. Several genes involved in oxidoreductive homeostasis were
      found to have higher expression levels in CSSL50-1 as well, suggesting potential
      roles of ROS in grain chalkiness formation. CONCLUSION: Extensive gene expression
      changes were detected during rice grain chalkiness formation. Over half of these
      differentially expressed genes are implicated in several important categories of
      genes, including signal transduction, transcription, carbohydrate metabolism and
      redox homeostasis, suggesting that chalkiness formation involves multiple
      metabolic and regulatory pathways.

PMID- 21192809
TI  - Under-ascertainment of Aboriginality in records of cardiovascular disease in
      hospital morbidity and mortality data in Western Australia: a record linkage
      study.
AB  - BACKGROUND: Measuring the real burden of cardiovascular disease in Australian
      Aboriginals is complicated by under-identification of Aboriginality in
      administrative health data collections. Accurate data is essential to measure
      Australia's progress in its efforts to intervene to improve health outcomes of
      Australian Aboriginals. We estimated the under-ascertainment of Aboriginal status
      in linked morbidity and mortality databases in patients hospitalised with
      cardiovascular disease. METHODS: Persons with public hospital admissions for
      cardiovascular disease in Western Australia during 2000-2005 (and their 20-year
      admission history) or who subsequently died were identified from linkage data.
      The Aboriginal status flag in all records for a given individual was variously
      used to determine their ethnicity (index positive, and in all records both
      majority positive or ever positive) and stratified by region, age and gender. The
      index admission was the baseline comparator. RESULTS: Index cases comprised
      62,692 individuals who shared a total of 778,714 hospital admissions over 20
      years, of which 19,809 subsequently died. There were 3,060 (4.9%) persons
      identified as Aboriginal on index admission. An additional 83 (2.7%) Aboriginal
      cases were identified through death records, increasing to 3.7% when cases with a
      positive Aboriginal identifier in the majority (>=50%) of previous hospital
      admissions over twenty years were added and by 20.8% when those with a positive
      flag in any record over 20 years were incorporated. These results equated to
      underestimating Aboriginal status in unlinked index admission by 2.6%, 3.5% and
      17.2%, respectively. Deaths classified as Aboriginal in official records would
      underestimate total Aboriginal deaths by 26.8% (95% Confidence Interval 24.1 to
      29.6%). CONCLUSIONS: Combining Aboriginal determinations in morbidity and
      official death records increases ascertainment of unlinked cardiovascular
      morbidity in Western Australian Aboriginals. Under-identification of Aboriginal
      status is high in death records.

PMID- 21192808
TI  - Mood after stroke: a case control study of biochemical, neuro-imaging and socio
      economic risk factors for major depression in stroke survivors.
AB  - BACKGROUND: Though vascular factors may be important in the aetiology of late
      life depression, it is not clear whether they have a major effect on the risk of
      depression after a stroke. We investigated the relationship between
      physiological, biochemical, neuro-imaging and socio-economic factors and late
      phase post-stroke depression in a cross-sectional case-control study. METHODS:
      People living at home at least 9 months after a stroke were interviewed using a
      structured proforma. Depression was diagnosed according to DSM-IV criteria,
      together with a Montgomery Asberg (MADRS) score >17. Stroke survivors of similar
      age and functional status but without symptoms of, or recent treatment for,
      depression and with MADRS score <7, were recruited as controls. RESULTS: Stroke
      survivors with depression were more likely than controls to have been smokers, to
      have had hypertension or peripheral arterial disease, and to have had more than
      one stroke or multiple discrete brainscan lesions. In univariate analysis they
      had significantly higher blood pressure, lower Mini-Mental State (MMSE) scores,
      higher serum homocysteine and lower folate levels, as well as more extensive
      white matter and basal ganglia changes on brainscan. In logistic regression,
      previous hypertension (OR 3.4), peripheral vascular disease (OR 4.7), number of
      strokes (OR 2), MMSE score (OR 0.76) and basal ganglia changes (OR 2.2), were
      independently associated with depression. CONCLUSION: These results suggest that
      patients with hypertension, hyperhomocysteinaemia and other factors associated
      with cerebral small vessel disease, may be more susceptible to post-stroke
      depression. Future intervention trials should focus on such high risk groups.

PMID- 21192810
TI  - The Vibrio parahaemolyticus Type III Secretion Systems manipulate host cell MAPK
      for critical steps in pathogenesis.
AB  - BACKGROUND: Vibrio parahaemolyticus is a food-borne pathogen causing inflammation
      of the gastrointestinal epithelium. Pathogenic strains of this bacterium possess
      two Type III Secretion Systems (TTSS) that deliver effector proteins into host
      cells. In order to better understand human host cell responses to V.
      parahaemolyticus, the modulation of Mitogen Activated Protein Kinase (MAPK)
      activation in epithelial cells by an O3:K6 clinical isolate, RIMD2210633, was
      investigated. The importance of MAPK activation for the ability of the bacterium
      to be cytotoxic and to induce secretion of Interleukin-8 (IL-8) was determined.
      RESULTS: V. parahaemolyticus deployed its TTSS1 to induce activation of the JNK,
      p38 and ERK MAPK in human epithelial cells. VP1680 was identified as the TTSS1
      effector protein responsible for MAPK activation in Caco-2 cells and the
      activation of JNK and ERK by this protein was important in induction of host cell
      death. V. parahaemolyticus actively induced IL-8 secretion in a response mediated
      by TTSS1. A role for VP1680 and for the ERK signalling pathway in the stimulation
      of IL-8 production in epithelial cells by V. parahaemolyticus was established.
      Interestingly, TTSS2 inhibited IL-8 mRNA transcription at early stages of
      interaction between the bacterium and the cell. CONCLUSIONS: This study
      demonstrated that V. parahaemolyticus activates the three major MAPK signalling
      pathways in intestinal epithelial cells in a TTSS1-dependent manner that involves
      the TTSS1 effector VP1680. Furthermore VP1680 and JNK and ERK activation were
      needed for maximal cytotoxicity of the bacterium. It was shown that V.
      parahaemolyticus is a strong inducer of IL-8 secretion and that induction
      reflects a balance between the effects of TTSS1 and TTSS2. Increases in IL-8
      secretion were mediated by TTSS1 and VP1680, and augmented by ERK activation.
      These results shed light on the mechanisms of bacterial pathogenesis mediated by
      TTSS and suggest significant roles for MAPK signalling during infection with V.
      parahaemolyticus.

PMID- 21192811
TI  - All Our Babies Cohort Study: recruitment of a cohort to predict women at risk of
      preterm birth through the examination of gene expression profiles and the
      environment.
AB  - BACKGROUND: Preterm birth is the leading cause of perinatal morbidity and
      mortality. Risk factors for preterm birth include a personal or familial history
      of preterm delivery, ethnicity and low socioeconomic status yet the ability to
      predict preterm delivery before the onset of preterm labour evades clinical
      practice. Evidence suggests that genetics may play a role in the multi-factorial
      pathophysiology of preterm birth. The All Our Babies Study is an on-going
      community based longitudinal cohort study that was designed to establish a cohort
      of women to investigate how a women's genetics and environment contribute to the
      pathophysiology of preterm birth. Specifically this study will examine the
      predictive potential of maternal leukocytes for predicting preterm birth in non
      labouring women through the examination of gene expression profiles and gene
      environment interactions. METHODS/DESIGN: Collaborations have been established
      between clinical lab services, the provincial health service provider and
      researchers to create an interdisciplinary study design for the All Our Babies
      Study. A birth cohort of 2000 women has been established to address this research
      question. Women provide informed consent for blood sample collection, linkage to
      medical records and complete questionnaires related to prenatal health, service
      utilization, social support, emotional and physical health, demographics, and
      breast and infant feeding. Maternal blood samples are collected in PAXgeneTM RNA
      tubes between 18-22 and 28-32 weeks gestation for transcriptomic analyses.
      DISCUSSION: The All Our Babies Study is an example of how investment in clinical
      academic-community partnerships can improve research efficiency and accelerate
      the recruitment and data collection phases of a study. Establishing these
      partnerships during the study design phase and maintaining these relationships
      through the duration of the study provides the unique opportunity to investigate
      the multi-causal factors of preterm birth. The overall All Our Babies Study
      results can potentially lead to healthier pregnancies, mothers, infants and
      children.

PMID- 21192813
TI  - SIDEKICK: Genomic data driven analysis and decision-making framework.
AB  - BACKGROUND: Scientists striving to unlock mysteries within complex biological
      systems face myriad barriers in effectively integrating available information to
      enhance their understanding. While experimental techniques and available data
      sources are rapidly evolving, useful information is dispersed across a variety of
      sources, and sources of the same information often do not use the same format or
      nomenclature. To harness these expanding resources, scientists need tools that
      bridge nomenclature differences and allow them to integrate, organize, and
      evaluate the quality of information without extensive computation. RESULTS:
      Sidekick, a genomic data driven analysis and decision making framework, is a web
      based tool that provides a user-friendly intuitive solution to the problem of
      information inaccessibility. Sidekick enables scientists without training in
      computation and data management to pursue answers to research questions like
      "What are the mechanisms for disease X" or "Does the set of genes associated with
      disease X also influence other diseases." Sidekick enables the process of
      combining heterogeneous data, finding and maintaining the most up-to-date data,
      evaluating data sources, quantifying confidence in results based on evidence, and
      managing the multi-step research tasks needed to answer these questions. We
      demonstrate Sidekick's effectiveness by showing how to accomplish a complex
      published analysis in a fraction of the original time with no computational
      effort using Sidekick. CONCLUSIONS: Sidekick is an easy-to-use web-based tool
      that organizes and facilitates complex genomic research, allowing scientists to
      explore genomic relationships and formulate hypotheses without computational
      effort. Possible analysis steps include gene list discovery, gene-pair list
      discovery, various enrichments for both types of lists, and convenient list
      manipulation. Further, Sidekick's ability to characterize pairs of genes offers
      new ways to approach genomic analysis that traditional single gene lists do not,
      particularly in areas such as interaction discovery.

PMID- 21192812
TI  - Reappraising the concept of massive transfusion in trauma.
AB  - INTRODUCTION: The massive-transfusion concept was introduced to recognize the
      dilutional complications resulting from large volumes of packed red blood cells
      (PRBCs). Definitions of massive transfusion vary and lack supporting clinical
      evidence. Damage-control resuscitation regimens of modern trauma care are
      targeted to the early correction of acute traumatic coagulopathy. The aim of this
      study was to identify a clinically relevant definition of trauma massive
      transfusion based on clinical outcomes. We also examined whether the concept was
      useful in that early prediction of massive transfusion requirements could allow
      early activation of blood bank protocols. METHODS: Datasets on trauma admissions
      over a 1 or 2-year period were obtained from the trauma registries of five large
      trauma research networks. A fractional polynomial was used to model the
      transfusion-associated probability of death. A logistic regression model for the
      prediction of massive transfusion, defined as 10 or more units of red cell
      transfusions, was developed. RESULTS: In total, 5,693 patient records were
      available for analysis. Mortality increased as transfusion requirements
      increased, but the model indicated no threshold effect. Mortality was 9% in
      patients who received none to five PRBC units, 22% in patients receiving six to
      nine PRBC units, and 42% in patients receiving 10 or more units. A logistic model
      for prediction of massive transfusion was developed and validated at multiple
      sites but achieved only moderate performance. The area under the receiver
      operating characteristic curve was 0.81, with specificity of only 50% at a
      sensitivity of 90% for the prediction of 10 or more PRBC units. Performance
      varied widely at different trauma centers, with specificity varying from 48% to
      91%. CONCLUSIONS: No threshold for definition exists at which a massive
      transfusion specifically results in worse outcomes. Even with a large sample size
      across multiple trauma datasets, it was not possible to develop a transportable
      and clinically useful prediction model based on available admission parameters.
      Massive transfusion as a concept in trauma has limited utility, and emphasis
      should be placed on identifying patients with massive hemorrhage and acute
      traumatic coagulopathy.

PMID- 21192814
TI  - The effect of acyclovir on the tubular secretion of creatinine in vitro.
AB  - BACKGROUND: While generally well tolerated, severe nephrotoxicity has been
      observed in some children receiving acyclovir. A pronounced elevation in plasma
      creatinine in the absence of other clinical manifestations of overt
      nephrotoxicity has been frequently documented. Several drugs have been shown to
      increase plasma creatinine by inhibiting its renal tubular secretion rather than
      by decreasing glomerular filtration rate (GFR). Creatinine and acyclovir may be
      transported by similar tubular transport mechanisms, thus, it is plausible that
      in some cases, the observed increase in plasma creatinine may be partially due to
      inhibition of tubular secretion of creatinine, and not solely due to decreased
      GFR. Our objective was to determine whether acyclovir inhibits the tubular
      secretion of creatinine. METHODS: Porcine (LLC-PK1) and human (HK-2) renal
      proximal tubular cell monolayers cultured on microporous membrane filters were
      exposed to [2-14C] creatinine (5 MUM) in the absence or presence of quinidine
      (1E+03 MUM), cimetidine (1E+03 MUM) or acyclovir (22-89 MUM) in incubation
      medium. RESULTS: Results illustrated that in evident contrast to quinidine,
      acyclovir did not inhibit creatinine transport in LLC-PK1 and HK-2 cell
      monolayers. CONCLUSIONS: The results suggest that acyclovir does not affect the
      renal tubular handling of creatinine, and hence, the pronounced, transient
      increase in plasma creatinine is due to decreased GFR, and not to a spurious
      increase in plasma creatinine.

PMID- 21192815
TI  - Right coronary wall CMR in the older asymptomatic advance cohort: positive
      remodeling and associations with type 2 diabetes and coronary calcium.
AB  - BACKGROUND: Coronary wall cardiovascular magnetic resonance (CMR) is a promising
      noninvasive approach to assess subclinical atherosclerosis, but data are limited
      in subjects over 60 years old, who are at increased risk. The purpose of the
      study was to evaluate coronary wall CMR in an asymptomatic older cohort. RESULTS:
      Cross-sectional images of the proximal right coronary artery (RCA) were acquired
      using spiral black-blood coronary CMR (0.7 mm resolution) in 223 older, community
      based patients without a history of cardiovascular disease (age 60-72 years old,
      38% female). Coronary measurements (total vessel area, lumen area, wall area, and
      wall thickness) had small intra- and inter-observer variabilities (r = 0.93~0.99,
      all p < 0.0001), though one-third of these older subjects had suboptimal image
      quality. Increased coronary wall thickness correlated with increased coronary
      vessel area (p < 0.0001), consistent with positive remodeling. On multivariate
      analysis, type 2 diabetes was the only risk factor associated with increased
      coronary wall area and thickness (p = 0.03 and p = 0.007, respectively). Coronary
      wall CMR measures were also associated with coronary calcification (p = 0.01
      0.03). CONCLUSIONS: Right coronary wall CMR in asymptomatic older subjects showed
      increased coronary atherosclerosis in subjects with type 2 diabetes as well as
      coronary calcification. Coronary wall CMR may contribute to the noninvasive
      assessment of subclinical coronary atherosclerosis in older, at-risk patient
      groups.

PMID- 21192816
TI  - iASPP is over-expressed in human non-small cell lung cancer and regulates the
      proliferation of lung cancer cells through a p53 associated pathway.
AB  - BACKGROUND: iASPP is a key inhibitor of tumour suppressor p53 and is found to be
      up-regulated in certain malignant conditions. The present study investigated the
      expression of iASPP in clinical lung cancer, a leading cancer type in the world,
      and the biological impact of this molecule on lung cancer cells. METHODS: iASPP
      protein levels in lung cancer tissues were evaluated using an immunohistochemical
      method. In vitro, iASPP gene expression was suppressed with a lentvirus-mediated
      shRNA method and the biological impact after knocking down iASSP on lung cancer
      cell lines was investigated in connection with the p53 expression status.
      RESULTS: We showed here that the expression of iASPP was significantly higher in
      lung cancer tissues compared with the adjacent normal tissues. iASPP shRNA
      treatment resulted in a down-regulation of iASPP in lung cancer cells. There was
      a subsequent reduction of cell proliferation of the two lung tumour cell lines
      A459 and 95D both of which had wild-type p53 expression. In contrast, reduction
      of iASPP in H1229 cells, a cell with little p53 expression, had no impact on its
      growth rate. CONCLUSIONS: iASPP regulates the proliferation and motility of lung
      cancer cells. This effect is intimately associated with the p53 pathway. Together
      with the pattern of the over-expression in clinical lung cancers, it is concluded
      that iASPP plays an pivotal role in the progression of lung cancer and is a
      potential target for lung cancer therapy.

PMID- 21192817
TI  - Fidelity of implementation: development and testing of a measure.
AB  - BACKGROUND: Along with the increasing prevalence of chronic illness has been an
      increase in interventions, such as nurse case management programs, to improve
      outcomes for patients with chronic illness. Evidence supports the effectiveness
      of such interventions in reducing patient morbidity, mortality, and resource
      utilization, but other studies have produced equivocal results. Often, little is
      known about how implementation of an intervention actually occurs in clinical
      practice. While studies often assume that interventions are used in clinical
      practice exactly as originally designed, this may not be the case. Thus, fidelity
      of an intervention's implementation reflects how an intervention is, or is not,
      used in clinical practice and is an important factor in understanding
      intervention effectiveness and in replicating the intervention in dissemination
      efforts. The purpose of this paper is to contribute to the understanding of
      implementation science by (a) proposing a methodology for measuring fidelity of
      implementation (FOI) and (b) testing the measure by examining the association
      between FOI and intervention effectiveness. METHODS: We define and measure FOI
      based on organizational members' level of commitment to using the distinct
      components that make up an intervention as they were designed. Semistructured
      interviews were conducted among 18 organizational members in four medical
      centers, and the interviews were analyzed qualitatively to assess three
      dimensions of commitment to use--satisfaction, consistency, and quality--and to
      develop an overall rating of FOI. Mixed methods were used to explore the
      association between FOI and intervention effectiveness (inpatient resource
      utilization and mortality). RESULTS: Predictive validity of the FOI measure was
      supported based on the statistical significance of FOI as a predictor of
      intervention effectiveness. The strongest relationship between FOI and
      intervention effectiveness was found when an alternative measure of FOI was
      utilized based on individual intervention components that had the greatest
      variation across medical centers. CONCLUSIONS: In addition to contextual factors,
      implementation research needs to consider FOI as an important factor in
      influencing intervention effectiveness. Our proposed methodology offers a
      systematic means for understanding organizational members' use of distinct
      intervention components, assessing the reasons for variation in use across
      components and organizations, and evaluating the impact of FOI on intervention
      effectiveness.

PMID- 21192818
TI  - Human articular chondrocytes express ChemR23 and chemerin; ChemR23 promotes
      inflammatory signalling upon binding the ligand chemerin(21-157).
AB  - INTRODUCTION: Chemerin is a chemotactic peptide which directs leukocytes
      expressing the chemokine-like receptor ChemR23 towards sites of inflammation.
      ChemR23 is a G protein-coupled receptor which binds several different ligands,
      and it is also expressed by other cell types such as adipocytes. In addition to
      chemotaxis, recent reports suggest that ChemR23 is capable of mediating either
      inflammatory or anti-inflammatory effects, depending on the type of ligand it
      binds. In the present study, we aimed to clarify whether human chondrocytes
      express ChemR23 and chemerin, and whether chemerin/ChemR23 signalling could
      affect secretion of inflammatory mediators. METHODS: Tissue sections were taken
      from human knee joints and labelled with antibodies towards chemerin and ChemR23.
      Chondrocytes from cartilage tissue were isolated, cultured and assessed for
      chemerin and ChemR23 expression by PCR and immunolabelling. Receptor activation
      and intracellular signalling were studied by assessment of phosphorylated mitogen
      activated protein kinases (MAPKs) and phosphorylated Akt after stimulating cells
      with recombinant chemerin(21-157). Biological effects of chemerin(21-157) were
      investigated by measuring secretion of pro-inflammatory cytokines and
      metalloproteases in cell supernatants. RESULTS: Both serially cultured human
      articular chondrocytes and resident cells in native cartilage expressed chemerin
      and ChemR23. Stimulating cells with chemerin(21-157) resulted in phosphorylation
      of p44/p42 MAPKs (ERK 1/2) and Akt (Ser 473). Also, significantly enhanced levels
      of the pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8),
      tumour necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and the
      matrix metalloproteases MMP-1, MMP-2, MMP-3, MMP-8 and MMP-13 were detected.
      CONCLUSIONS: These results demonstrate that human chondrocytes express both the
      receptor ChemR23 and the ligand chemerin. Chemerin(21-157) stimulation engaged
      signal-transduction pathways that further promoted inflammatory signalling in
      chondrocytes, as judged by an enhanced secretion of cytokines and
      metalloproteases. Taken together, the previously reported chemotaxis and the
      present findings suggest that the receptor and its ligand may play pivotal roles
      in joint inflammation.

PMID- 21192819
TI  - Transient expression of betaC1 protein differentially regulates host genes
      related to stress response, chloroplast and mitochondrial functions.
AB  - BACKGROUND: Geminiviruses are emerging plant pathogens that infect a wide variety
      of crops including cotton, cassava, vegetables, ornamental plants and cereals.
      The geminivirus disease complex consists of monopartite begomoviruses that
      require betasatellites for the expression of disease symptoms. These complexes
      are widespread throughout the Old World and cause economically important diseases
      on several crops. A single protein encoded by betasatellites, termed betaC1, is a
      suppressor of gene silencing, inducer of disease symptoms and is possibly
      involved in virus movement. Studies of the interaction of betaC1 with hosts can
      provide useful insight into virus-host interactions and aid in the development of
      novel control strategies. We have used the differential display technique to
      isolate host genes which are differentially regulated upon transient expression
      of the betaC1 protein of chili leaf curl betasatellite (ChLCB) in Nicotiana
      tabacum. RESULTS: Through differential display analysis, eight genes were
      isolated from Nicotiana tabacum, at two and four days after infiltration with
      betaC1 of ChLCB, expressed under the control of the Cauliflower mosaic virus 35S
      promoter. Cloning and sequence analysis of differentially amplified products
      suggested that these genes were involved in ATP synthesis, and acted as electron
      carriers for respiration and photosynthesis processes. These differentially
      expressed genes (DEGs) play an important role in plant growth and development,
      cell protection, defence processes, replication mechanisms and detoxification
      responses. Kegg orthology based annotation system analysis of these DEGs
      demonstrated that one of the genes, coding for polynucleotide nucleotidyl
      transferase, is involved in purine and pyrimidine metabolic pathways and is an
      RNA binding protein which is involved in RNA degradation. CONCLUSION: betaC1
      differentially regulated genes are mostly involved in chloroplast and
      mitochondrial functions. betaC1 also increases the expression of those genes
      which are involved in purine and pyrimidine metabolism. This information gives a
      new insight into the interaction of betaC1 with the host and can be used to
      understand host-virus interactions in follow-up studies.

PMID- 21192820
TI  - Rice hypersensitive induced reaction protein 1 (OsHIR1) associates with plasma
      membrane and triggers hypersensitive cell death.
AB  - BACKGROUND: In plants, HIR (Hypersensitive Induced Reaction) proteins, members of
      the PID (Proliferation, Ion and Death) superfamily, have been shown to play a
      part in the development of spontaneous hypersensitive response lesions in leaves,
      in reaction to pathogen attacks. The levels of HIR proteins were shown to
      correlate with localized host cell deaths and defense responses in maize and
      barley. However, not much was known about the HIR proteins in rice. Since rice is
      an important cereal crop consumed by more than 50% of the populations in Asia and
      Africa, it is crucial to understand the mechanisms of disease responses in this
      plant. We previously identified the rice HIR1 (OsHIR1) as an interacting partner
      of the OsLRR1 (rice Leucine-Rich Repeat protein 1). Here we show that OsHIR1
      triggers hypersensitive cell death and its localization to the plasma membrane is
      enhanced by OsLRR1. RESULT: Through electron microscopy studies using wild type
      rice plants, OsHIR1 was found to mainly localize to the plasma membrane, with a
      minor portion localized to the tonoplast. Moreover, the plasma membrane
      localization of OsHIR1 was enhanced in transgenic rice plants overexpressing its
      interacting protein partner, OsLRR1. Co-localization of OsHIR1 and OsLRR1 to the
      plasma membrane was confirmed by double-labeling electron microscopy. Pathogen
      inoculation studies using transgenic Arabidopsis thaliana expressing either
      OsHIR1 or OsLRR1 showed that both transgenic lines exhibited increased resistance
      toward the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. However,
      OsHIR1 transgenic plants produced more extensive spontaneous hypersensitive
      response lesions and contained lower titers of the invading pathogen, when
      compared to OsLRR1 transgenic plants. CONCLUSION: The OsHIR1 protein is mainly
      localized to the plasma membrane, and its subcellular localization in that
      compartment is enhanced by OsLRR1. The expression of OsHIR1 may sensitize the
      plant so that it is more prone to HR and hence can react more promptly to limit
      the invading pathogens' spread from the infection sites.

PMID- 21192821
TI  - Protein kinase C and rho activated coiled coil protein kinase 2 (ROCK2) modulate
      Alzheimer's APP metabolism and phosphorylation of the Vps10-domain protein,
      SorL1.
AB  - BACKGROUND: Generation of the amyloid beta (Abeta) peptide of Alzheimer's disease
      (AD) is differentially regulated through the intracellular trafficking of the
      amyloid beta precursor protein (APP) within the secretory and endocytic pathways.
      Protein kinase C (PKC) and rho-activated coiled-coil kinases (ROCKs) are two
      "third messenger" signaling molecules that control the relative utilization of
      these two pathways. Several members of the Vps family of receptors (Vps35, SorL1,
      SorCS1) play important roles in post-trans-Golgi network (TGN) sorting and
      generation of APP derivatives, including Abeta at the TGN, endosome and the
      plasma membrane. We now report that Vps10-domain proteins are candidate
      substrates for PKC and/or ROCK2 and act as phospho-state-sensitive physiological
      effectors for post-TGN sorting of APP and its derivatives. RESULTS: Analysis of
      the SorL1 cytoplasmic tail revealed multiple consensus sites for phosphorylation
      by protein kinases. SorL1 was subsequently identified as a phosphoprotein, based
      on sensitivity of its electrophoretic migration pattern to calf intestine
      alkaline phosphatase and on its reaction with anti-phospho-serine antibodies.
      Activation of PKC resulted in increased shedding of the ectodomains of both APP
      and SorL1, and this was paralleled by an apparent increase in the level of the
      phosphorylated form of SorL1. ROCK2, the neuronal isoform of another protein
      kinase, was found to form complexes with SorL1, and both ROCK2 inhibition and
      ROCK2 knockdown enhanced generation of both soluble APP and Abeta. CONCLUSION:
      These results highlight the potential importance of SorL1 in elucidating phospho
      state sensitive mechanisms in the regulation of metabolism of APP and Abeta by
      PKC and ROCK2.

PMID- 21192822
TI  - Abnormal cortical responses to somatosensory stimulation in medication-overuse
      headache.
AB  - BACKGROUND: Medication-overuse headache (MOH) is a frequent, disabling disorder.
      Despite a controversial pathophysiology convincing evidence attributes a pivotal
      role to central sensitization. Most patients with MOH initially have episodic
      migraine without aura (MOA) characterized interictally by an absent amplitude
      decrease in cortical evoked potentials to repetitive stimuli (habituation
      deficit), despite a normal initial amplitude (lack of sensitization). Whether
      central sensitization alters this electrophysiological profile is unknown. We
      therefore sought differences in somatosensory evoked potential (SEP)
      sensitization and habituation in patients with MOH and episodic MOA. METHODS: We
      recorded median-nerve SEPs (3 blocks of 100 sweeps) in 29 patients with MOH, 64
      with MOA and 42 controls. Episodic migraineurs were studied during and between
      attacks. We measured N20-P25 amplitudes from 3 blocks of 100 sweeps, and assessed
      sensitization from block 1 amplitude, and habituation from amplitude changes
      between the 3 sequential blocks. RESULTS: In episodic migraineurs, interictal SEP
      amplitudes were normal in block 1, but thereafter failed to habituate. Ictal SEP
      amplitudes increased in block 1, then habituated normally. Patients with MOH had
      larger-amplitude block 1 SEPs than controls, and also lacked SEP habituation. SEP
      amplitudes were smaller in triptan overusers than in patients overusing
      nonsteroidal anti-inflammatory drugs (NSAIDs) or both medications combined,
      lowest in patients with the longest migraine history, and highest in those with
      the longest-lasting headache chronification. CONCLUSIONS: In patients with MOH,
      especially those overusing NSAIDs, the somatosensory cortex becomes increasingly
      sensitized. Sensory sensitization might add to the behavioral sensitization that
      favors compulsive drug intake, and may reflect drug-induced changes in central
      serotoninergic transmission.

PMID- 21192823
TI  - HaloWeb: the haloarchaeal genomes database.
AB  - BACKGROUND: Complete genome sequencing together with post-genomic studies provide
      the opportunity for a comprehensive 'systems biology' understanding of model
      organisms. For maximum effectiveness, an integrated database containing genomic,
      transcriptomic, and proteomic data is necessary. DESCRIPTION: To improve data
      access and facilitate functional genomic studies on haloarchaea in our
      laboratory, a dedicated database and website, named HaloWeb, was developed. It
      incorporates all finished and publicly released haloarchaeal genomes, including
      gene, protein and RNA sequences and annotation data, as well as other features
      such as insertion element sequences. The HaloWeb database was designed for easy
      data access and mining, and includes tools for tasks such as genome map
      generation, sequence extraction, and sequence editing. Popular resources at other
      sites, e.g., NCBI PubMed and BLAST, COG and KOG protein clusters, KEGG pathways,
      and GTOP structures were dynamically linked. The HaloWeb site is located at
      http://halo4.umbi.umd.edu, and at a mirror site, http://halo5.umbi.umd.edu, with
      all public genomic data and NCBI, KEGG, and GTOP links available for use by the
      academic community. The database is curated and updated on a regular basis.
      CONCLUSIONS: The HaloWeb site includes all completely sequenced haloarchaeal
      genomes from public databases. It is currently being used as a tool for
      comparative genomics, including analysis of gene and genome structure,
      organization, and function. The database and website are up-to-date resources for
      researchers worldwide.

PMID- 21192824
TI  - Complementary monoclonal antibody-based dot ELISA for universal detection of H5
      avian influenza virus.
AB  - BACKGROUND: Rapid diagnosis and surveillance for H5 subtype viruses are critical
      for the control of H5N1 infection. RESULTS: In this study, H5 Dot ELISA, a rapid
      test for the detection of avian H5N1 influenza virus, was developed with two
      complementary H5 monoclonal antibodies. HA sequencing of escape mutants followed
      by epitope mapping revealed that the two Mabs target the epitope component (189th
      amino acid) on the HA protein but are specific for different amino acids (189Lys
      or 189Arg). Gene alignment indicated that these two amino acids are the most
      frequent types on this position among all of the H5 AIV reported in GeneBank.
      These two H5 Mabs were used together in a dot ELISA to detect H5 viral antigen.
      The detection limit of the developed test for multiple clades of H5N1 viruses,
      including clades 0, 1, 2.1, 2.2, 2.3, 4, 7, and 8, was less than 0.5
      hemagglutinin units. The specificity of the optimized dot ELISA was examined by
      using 100 H5 strains, including H5N1 HPAI strains from multiple clades, 36 non
      H5N1 viruses, and 4 influenza B viruses. No cross-reactivity was observed for any
      of the non-H5N1 viruses tested. Among 200 random poultry samples, the test gave
      100% positive results for all of the twelve RT-PCR-positive samples. CONCLUSIONS:
      Considering that the test is convenient for field use, this H5 Dot ELISA can be
      used for on-site detection of H5N1 infection in clinical or environmental
      specimens and facilitate the investigation of H5N1 influenza outbreaks and
      surveillance in poultry.

PMID- 21192825
TI  - Factors affecting treatment-seeking for febrile illness in a malaria endemic
      block in Boudh district, Orissa, India: policy implications for malaria control.
AB  - BACKGROUND: Orissa state in eastern India accounts for the highest malaria burden
      to the nation. However, evidences are limited on its treatment-seeking behaviour
      in the state. We assessed the treatment-seeking behaviour towards febrile illness
      in a malaria endemic district in Orissa. METHODS: A cross-sectional community
      based survey was carried out during the high malaria transmission season of 2006
      in Boudh district. Respondents (n = 300) who had fever with chills within two
      weeks prior to the day of data collection were selected through a multi-stage
      sampling and interviewed with a pre-tested and structured interview schedule.
      Malaria treatment providers (n = 23) were interviewed in the district to gather
      their insights on factors associated with prompt and effective treatment through
      a semi-structured and open-ended interview guideline. RESULTS: Majority of
      respondents (n = 281) sought some sort of treatment e.g. government health
      facility (35.7%), less qualified providers (31.3%), and community level health
      workers and volunteers (24.3%). The single most common reason (66.9%) for
      choosing a provider was proximity. Over a half (55.7%) sought treatment from
      appropriate providers within 48 hours of onset of symptoms. Respondents under
      five years (OR 2.00, 95% CI 0.84-4.80, P = 0.012), belonging to scheduled tribe
      community (OR 2.13, 95% CI 1.11-4.07, P = 0.022) and visiting a provider more
      than five kilometers (OR 2.04, 95% CI 1.09-3.83, P = 0.026) were more likely to
      have delayed or inappropriate treatment. Interviews with the providers indicated
      that patients' lack of trust in community volunteers providing treatment led to
      inappropriate treatment-seeking from the less qualified providers. The reasons
      for the lack of trust included drug side effects, suspicions about drug quality,
      stock-outs of drugs and inappropriate attitude of the provider. CONCLUSION: Large
      scale involvement of less qualified providers is suggested in the malaria control
      programme as volunteers after appropriate capacity development since the
      community has more trust in them. This should be supported by uninterrupted
      supply of drugs to the community volunteers, and involvement of the community
      based organizations and volunteers in the planning, implementation, and
      monitoring of malaria control services. There is also a need for continuous and
      rigorous impact evaluations of the program to make necessary modifications, scale
      up and to prevent drug resistance.

PMID- 21192826
TI  - Immunomodulatory effect of Hawthorn extract in an experimental stroke model.
AB  - BACKGROUND: Recently, we reported a neuroprotective effect for Hawthorn
      (Crataegus oxyacantha) ethanolic extract in middle cerebral artery occlusion
      (MCAO) induced stroke in rats. The present study sheds more light on the
      extract's mechanism of neuroprotection, especially its immunomodulatory effect.
      METHODS: After 15 days of treatment with Hawthorn extract [100 mg/kg,
      pretreatment (oral)], male Sprague Dawley rats underwent transient MCAO for 75
      mins followed by reperfusion (either 3 or 24 hrs). We measured pro-inflammatory
      cytokines (IL-1beta, TNF-alpha, IL-6), ICAM-1, IL-10 and pSTAT-3 expression in
      the brain by appropriate methods. We also looked at the cytotoxic T cell sub
      population among leukocytes (FACS) and inflammatory cell activation and
      recruitment in brain (using a myeloperoxidase activity assay) after ischemia and
      reperfusion (I/R). Apoptosis (TUNEL), and Bcl-xL- and Foxp3- (T(reg) marker)
      positive cells in the ipsilateral hemisphere of the brain were analyzed
      separately using immunofluorescence. RESULTS: Our results indicate that occlusion
      followed by 3 hrs of reperfusion increased pro-inflammatory cytokine and ICAM-1
      gene expressions in the ipsilateral hemisphere, and that Hawthorn pre-treatment
      significantly (p <= 0.01) lowered these levels. Furthermore, such pre-treatment
      was able to increase IL-10 levels and Foxp3-positive cells in brain after 24 hrs
      of reperfusion. The increase in cytotoxic T cell population in vehicle rats after
      24 hrs of reperfusion was decreased by at least 40% with Hawthorn pretreatment.
      In addition, there was a decrease in inflammatory cell activation and
      infiltration in pretreated brain. Hawthorn pretreatment elevated pSTAT-3 levels
      in brain after I/R. We also observed an increase in Bcl-xL-positive cells, which
      in turn may have influenced the reduction in TUNEL-positive cells compared to
      vehicle-treated brain. CONCLUSIONS: In summary, Hawthorn extract helped alleviate
      pro-inflammatory immune responses associated with I/R-induced injury, boosted IL
      10 levels, and increased Foxp3-positive T(regs) in the brain, which may have
      aided in suppression of activated inflammatory cells. Such treatment also
      minimizes apoptotic cell death by influencing STAT-3 phosphorylation and Bcl-xL
      expression in the brain. Taken together, the immunomodulatory effect of Hawthorn
      extract may play a critical role in the neuroprotection observed in this MCAO
      induced stroke model.

PMID- 21192827
TI  - Conjugated polymer nanoparticles for effective siRNA delivery to tobacco BY-2
      protoplasts.
AB  - BACKGROUND: Post transcriptional gene silencing (PTGS) is a mechanism harnessed
      by plant biologists to knock down gene expression. siRNAs contribute to PTGS that
      are synthesized from mRNAs or viral RNAs and function to guide cellular
      endoribonucleases to target mRNAs for degradation. Plant biologists have employed
      electroporation to deliver artificial siRNAs to plant protoplasts to study gene
      expression mechanisms at the single cell level. One drawback of electroporation
      is the extensive loss of viable protoplasts that occurs as a result of the
      transfection technology. RESULTS: We employed fluorescent conjugated polymer
      nanoparticles (CPNs) to deliver siRNAs and knockdown a target gene in plant
      protoplasts. CPNs are non toxic to protoplasts, having little impact on viability
      over a 72 h period. Microscopy and flow cytometry reveal that CPNs can penetrate
      protoplasts within 2 h of delivery. Cellular uptake of CPNs/siRNA complexes were
      easily monitored using epifluorescence microscopy. We also demonstrate that CPNs
      can deliver siRNAs targeting specific genes in the cellulose biosynthesis pathway
      (NtCesA-1a and NtCesA-1b). CONCLUSIONS: While prior work showed that NtCesA-1 is
      a factor involved in cell wall synthesis in whole plants, we demonstrate that the
      same gene plays an essential role in cell wall regeneration in isolated
      protoplasts. Cell wall biosynthesis is central to cell elongation, plant growth
      and development. The experiments presented here shows that NtCesA is also a
      factor in cell viability. We show that CPNs are valuable vehicles for delivering
      siRNAs to plant protoplasts to study vital cellular pathways at the single cell
      level.

PMID- 21192828
TI  - Stable coexistence of two Caldicellulosiruptor species in a de novo constructed
      hydrogen-producing co-culture.
AB  - BACKGROUND: Mixed culture enrichments have been used frequently for biohydrogen
      production from different feedstock. In spite of the several advantages offered
      by those cultures, they suffer poor H2 yield. Constructing defined co-cultures of
      known H2 producers may offer a better performance than mixed-population
      enrichments, while overcoming some of the limitations of pure cultures based on
      synergies among the microorganisms involved. RESULTS: The extreme thermophiles
      Caldicellulosiruptor saccharolyticus DSM 8903 and C. kristjanssonii DSM 12137
      were combined in a co-culture for H2 production from glucose and xylose in a
      continuous-flow stirred tank reactor. The co-culture exhibited a remarkable
      stability over a period of 70 days under carbon-sufficient conditions, with both
      strains coexisting in the system at steady states of different dilution rates, as
      revealed by species-specific quantitative PCR assays. The two strains retained
      their ability to stably coexist in the reactor even when glucose was used as the
      sole growth-limiting substrate. Furthermore, H2 yields on glucose exceeded those
      of either organism alone under the same conditions, alluding to a synergistic
      effect of the two strains on H2 production. A maximum H2 yield of 3.7 mol (mol
      glucose)(-1) was obtained by the co-culture at a dilution rate of 0.06 h(-1); a
      higher yield than that reported for any mixed culture to date. A reproducible
      pattern of population dynamics was observed in the co-culture under both carbon
      and non-carbon limited conditions, with C. kristjanssonii outgrowing C.
      saccharolyticus during the batch start-up phase and prevailing at higher dilution
      rates. A basic continuous culture model assuming the ability of C.
      saccharolyticus to enhance the growth of C. kristjanssonii could mimic the
      pattern of population dynamics observed experimentally and provide clues to the
      nature of interaction between the two strains. As a proof, the cell-free growth
      supernatant of C. saccharolyticus was found able to enhance the growth of C.
      kristjanssonii in batch culture through shortening its lag phase and increasing
      its maximum biomass concentration by ca. 18%. CONCLUSIONS: This study provides
      experimental evidence on the stable coexistence of two closely related organisms
      isolated from geographically-distant habitats under continuous operation
      conditions, with the production of H2 at high yields. An interspecies interaction
      is proposed as the reason behind the remarkable ability of the two
      Caldicellulosiruptor strains to coexist in the system rather than only competing
      for the growth-limiting substrate.

PMID- 21192829
TI  - Blood pressure control and antihypertensive pharmacotherapy patterns in a
      hypertensive population of Eastern Central Region of Portugal.
AB  - BACKGROUND: Interventions to improve blood pressure control in hypertension have
      had limited success in clinical practice despite evidence of cardiovascular
      disease prevention in randomised controlled trials.The objectives of this study
      were to evaluate blood pressure control and antihypertensive pharmacotherapy
      patterns in a population of Eastern Central Region of Portugal, attending a
      hospital outpatient clinic (ambulatory setting) for routine follow-up. METHODS:
      Medical data of all patients that attended at least two medical appointments of
      hypertension/dyslipidemia in a university hospital over a one and a half year
      period (from January 2008 to June 2009) were retrospectively analysed.
      Demographic variables, clinical data and blood pressure values of hypertensive
      patients included in the study, as well as prescribing metrics were examined on a
      descriptive basis and expressed as the mean +/- SD, frequency and percentages.
      Student's test and Mann-Whitney rank sum test were used to compare continuous
      variables and chi2 test and Fisher exact probability test were used to test for
      differences between categorical variables. RESULTS: In all, 37% of hypertensive
      patients (n = 76) had their blood pressure controlled according to international
      guidelines. About 45.5% of patients with a target blood pressure <140/90 mmHg (n
      = 156) were controlled, whereas in patients with diabetes or chronic kidney
      disease (n = 49) the corresponding figure was only 10.2% (P < 0.001). Among
      patients initiating hypertension/dyslipidemia consultation within the study
      period 32.1% had stage 2 hypertension in the first appointment, but this figure
      decreased to 3.6% in the last consultation (P = 0.012). Thiazide-type diuretics
      were the most prescribed antihypertensive drugs (67%) followed by angiotensin
      receptor blockers (60%) and beta-blockers (43%). About 95.9% patients with
      comorbid diabetes were treated with an angiotensin-converting enzyme inhibitor or
      an angiotensin receptor blocker. CONCLUSIONS: Clinically important blood pressure
      decreases can be achieved soon after hypertension medical appointment initiation.
      However, many hypertensive patients prescribed with antihypertensive therapy fail
      to achieve blood pressure control in clinical practice, this control being worse
      among patients with diabetes or chronic kidney disease. As pharmacotherapy
      patterns seem to coincide with international guidelines, further research is
      needed to identify the causes of poor blood pressure control.

PMID- 21192830
TI  - The prevalence of gene duplications and their ancient origin in Rhodobacter
      sphaeroides 2.4.1.
AB  - BACKGROUND: Rhodobacter sphaeroides 2.4.1 is a metabolically versatile organism
      that belongs to alpha-3 subdivision of Proteobacteria. The present study was to
      identify the extent, history, and role of gene duplications in R. sphaeroides
      2.4.1, an organism that possesses two chromosomes. RESULTS: A protein similarity
      search (BLASTP) identified 1247 orfs (~29.4% of the total protein coding orfs)
      that are present in 2 or more copies, 37.5% (234 gene-pairs) of which exist in
      duplicate copies. The distribution of the duplicate gene-pairs in all Clusters of
      Orthologous Groups (COGs) differed significantly when compared to the COG
      distribution across the whole genome. Location plots revealed clusters of gene
      duplications that possessed the same COG classification. Phylogenetic analyses
      were performed to determine a tree topology predicting either a Type-A or Type-B
      phylogenetic relationship. A Type-A phylogenetic relationship shows that a copy
      of the protein-pair matches more with an ortholog from a species closely related
      to R. sphaeroides while a Type-B relationship predicts the highest match between
      both copies of the R. sphaeroides protein-pair. The results revealed that ~77% of
      the proteins exhibited a Type-A phylogenetic relationship demonstrating the
      ancient origin of these gene duplications. Additional analyses on three other
      strains of R. sphaeroides revealed varying levels of gene loss and retention in
      these strains. Also, analyses on common gene pairs among the four strains
      revealed that these genes experience similar functional constraints and undergo
      purifying selection. CONCLUSIONS: Although the results suggest that the level of
      gene duplication in organisms with complex genome structuring (more than one
      chromosome) seems to be not markedly different from that in organisms with only a
      single chromosome, these duplications may have aided in genome reorganization in
      this group of eubacteria prior to the formation of R. sphaeroides as gene
      duplications involved in specialized functions might have contributed to complex
      genomic development.

PMID- 21192831
TI  - Cluster analysis for identifying sub-groups and selecting potential
      discriminatory variables in human encephalitis.
AB  - BACKGROUND: Encephalitis is an acute clinical syndrome of the central nervous
      system (CNS), often associated with fatal outcome or permanent damage, including
      cognitive and behavioural impairment, affective disorders and epileptic seizures.
      Infection of the central nervous system is considered to be a major cause of
      encephalitis and more than 100 different pathogens have been recognized as
      causative agents. However, a large proportion of cases have unknown disease
      etiology. METHODS: We perform hierarchical cluster analysis on a multicenter
      England encephalitis data set with the aim of identifying sub-groups in human
      encephalitis. We use the simple matching similarity measure which is appropriate
      for binary data sets and performed variable selection using cluster heatmaps. We
      also use heatmaps to visually assess underlying patterns in the data, identify
      the main clinical and laboratory features and identify potential risk factors
      associated with encephalitis. RESULTS: Our results identified fever, personality
      and behavioural change, headache and lethargy as the main characteristics of
      encephalitis. Diagnostic variables such as brain scan and measurements from
      cerebrospinal fluids are also identified as main indicators of encephalitis. Our
      analysis revealed six major clusters in the England encephalitis data set.
      However, marked within-cluster heterogeneity is observed in some of the big
      clusters indicating possible sub-groups. Overall, the results show that patients
      are clustered according to symptom and diagnostic variables rather than causal
      agents. Exposure variables such as recent infection, sick person contact and
      animal contact have been identified as potential risk factors. CONCLUSIONS: It is
      in general assumed and is a common practice to group encephalitis cases according
      to disease etiology. However, our results indicate that patients are clustered
      with respect to mainly symptom and diagnostic variables rather than causal
      agents. These similarities and/or differences with respect to symptom and
      diagnostic measurements might be attributed to host factors. The idea that
      characteristics of the host may be more important than the pathogen is also
      consistent with the observation that for some causes, such as herpes simplex
      virus (HSV), encephalitis is a rare outcome of a common infection.

PMID- 21192832
TI  - Rapid detection of porcine circovirus type 2 using a TaqMan-based real-time PCR.
AB  - Porcine circovirus type 2 (PCV2) and the associated disease postweaning
      multisystemic wasting syndrome (PMWS) have caused heavy losses in global
      agriculture in recent decades. Rapid detection of PCV2 is very important for the
      effective prophylaxis and treatment of PMWS. To establish a sensitive, specific
      assay for the detection and quantitation of PCV2, we designed and synthesized
      specific primers and a probe in the open reading frame 2. The assay had a wide
      dynamic range with excellent linearity and reliable reproducibility, and detected
      between 102 and 1010 copies of the genomic DNA per reaction. The coefficient of
      variation for Ct values varied from 0.59% to 1.05% in the same assay and from
      1.9% to 4.2% in 10 different assays. The assay did not cross-react with porcine
      circovirus type 1, porcine reproductive and respiratory, porcine epidemic
      diarrhea, transmissible gastroenteritis of pigs and rotavirus. The limits of
      detection and quantitation were 10 and 100 copies, respectively. Using the
      established real-time PCR system, 39 of the 40 samples we tested were detected as
      positive.

PMID- 21192833
TI  - Microarray-based analysis of microRNA expression in breast cancer stem cells.
AB  - BACKGROUND: This study aimed to determine the miRNA profile in breast cancer stem
      cells (BCSCs) and to explore the functions of characteristic BCSC miRNAs.
      METHODS: We isolated ESA+CD44+CD24-/low BCSCs from MCF-7 cells using fluorescence
      activated cell sorting (FACS). A human breast cancer xenograft assay was
      performed to validate the stem cell properties of the isolated cells, and
      microarray analysis was performed to screen for BCSC-related miRNAs. These BCSC
      related miRNAs were selected for bioinformatic analysis and target prediction
      using online software programs. RESULTS: The ESA+CD44+CD24-/low cells had up to
      100- to 1000-fold greater tumor-initiating capability than the MCF-7 cells.
      Tumors initiated from the ESA+CD44+CD24-/low cells were included of luminal
      epithelial and myoepithelial cells, indicating stem cell properties. We also
      obtained miRNA profiles of ESA+CD44+CD24-/low BCSCs. Most of the possible targets
      of potential tumorigenesis-related miRNAs were oncogenes, anti-oncogenes or
      regulatory genes. CONCLUSIONS: We identified a subset of miRNAs that were
      differentially expressed in BCSCs, providing a starting point to explore the
      functions of these miRNAs. Evaluating characteristic BCSC miRNAs represents a new
      method for studying breast cancer-initiating cells and developing therapeutic
      strategies aimed at eradicating the tumorigenic subpopulation of cells in breast
      cancer.

PMID- 21192834
TI  - Pyrethroid resistance in southern African Anopheles funestus extends to Likoma
      Island in Lake Malawi.
AB  - BACKGROUND: A mosquito survey was carried out on the island of Likoma in Lake
      Malawi with a view to collecting baseline data to determine the feasibility of
      implementing an integrated malaria vector control programme. No vector control
      interventions are currently being applied on the island apart from the sporadic
      use of treated and untreated bed nets. RESULTS: Large numbers of Anopheles
      funestus were found resting inside houses. WHO susceptibility tests were carried
      out on wild caught females and 1-5 day old F-1 female progeny. Wild caught
      females were tested on deltamethrin (77.8% mortality) and bendiocarb (56.4%
      mortality). Female progeny were tested on deltamethrin (41.4% mortality),
      permethrin (40.4%), bendiocarb (52.5%), propoxur (7.4%), malathion, fenitrothion,
      DDT, dieldrin (all 100%) and pirimiphos-methyl (98.9%). The malaria parasite rate
      was 4.9%. A small number of Anopheles arabiensis were also collected. CONCLUSION:
      This locality is 1,500 km north of the currently known distribution of pyrethroid
      resistant An. funestus in southern Africa. The susceptibility results mirror
      those found in southern Mozambique and South African populations, but are
      markedly different to An. funestus populations in Uganda, indicating that the
      Malawi resistance has spread from the south.

PMID- 21192835
TI  - Clinical proteomics for liver disease: a promising approach for discovery of
      novel biomarkers.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer and advanced
      hepatic fibrosis is a major risk factor for HCC. Hepatic fibrosis including liver
      cirrhosis and HCC are mainly induced by persistent hepatitis B or C virus
      infection, with approximately 500 million people infected with hepatitis B or C
      virus worldwide. Furthermore, the number of patients with non-alcoholic fatty
      liver disease (NAFLD) has recently increased and NAFLD can progress to cirrhosis
      and HCC. These chronic liver diseases are major causes of morbidity and
      mortality, and the identification of non-invasive biomarkers is important for
      early diagnosis. Recent advancements in quantitative and large-scale proteomic
      methods could be used to optimize the clinical application of biomarkers. Early
      diagnosis of HCC and assessment of the stage of hepatic fibrosis or NAFLD can
      also contribute to more effective therapeutic interventions and an improve
      prognosis. Furthermore, advancements of proteomic techniques contribute not only
      to the discovery of clinically useful biomarkers, but also in clarifying the
      molecular mechanisms of disease pathogenesis by using body fluids, such as serum,
      and tissue samples and cultured cells. In this review, we report recent advances
      in quantitative proteomics and several findings focused on liver diseases,
      including HCC, NAFLD, hepatic fibrosis and hepatitis B or C virus infections.

PMID- 21192836
TI  - The effect of aligned core-shell nanofibres delivering NGF on the promotion of
      sciatic nerve regeneration.
AB  - Recent bioengineering strategies for peripheral nerve regeneration have been
      focusing on the development of alternative treatments for nerve repair. In this
      study, we incorporated nerve growth factor (NGF) into aligned core-shell
      nanofibres by coaxial electrospinning, and reeled  the scaffold into aligned
      fibrous nerve guidance conduits (NGCs) for nerve regeneration study. This aligned
      PLGA/NGF NGC combined physical guidance cues and biomolecular signals to closely
      mimic the native extracellular matrix (ECM). The effect of this aligned PLGA/NGF
      NGC on the promotion  of nerve regeneration was evaluated in a 13-mm rat sciatic
      nerve defect using functional and morphological analysis. After 12 weeks
      implantation, the results of electrophysiological and muscle weight examination
      demonstrated that the functional recovery of the regenerated nerve in the
      PLGA/NGF  NGC group was significantly better than that in the PLGA group, yet had
      no significant difference compared with the autograft group. The toluidine blue
      staining study showed that more nerve fibres were regenerated in the PLGA/NGF
      group, while the electron microscopy study indicated that the  regenerated nerve
      in the PLGA/NGF group was more mature than that in the PLGA group. This study
      demonstrated that the aligned PLGA/NGF could greatly promote peripheral nerve
      regeneration and have a potential application in nerve regeneration.

PMID- 21192837
TI  - Enhanced angiogenic efficacy through controlled and sustained delivery of FGF-2
      and G-CSF from fibrin hydrogels containing ionic-albumin microspheres.
AB  - Neo-vessel formation in ischemic tissues relies on numerous growth factors and
      cell fractions for the formation of mature, stable, functional vasculature.
      However, the efforts to regenerate tissues typically rely on the administration
      of a single growth factor or cells alone. Conversely,  polymeric matrices have
      been investigated extensively to deliver multiple growth factors at pre
      determined rates to form stable blood vessels in ischemic tissues. We report on a
      novel sequential delivery system of a fibrin hydrogel containing ionic-albumin
      microspheres that allows for the  controlled release of two growth factors. The
      use of this system was investigated in the context of therapeutic angiogenesis.
      Material properties were determined based on degree of swelling measurements and
      degradation characteristics. Release kinetics of model angiogenic polypeptides
      FGF-2  and G-CSF were determined using ELISA and the bioactivity of released
      protein was evaluated in human endothelial cell cultures. The release of growth
      factors from ionic-albumin microspheres was significantly delayed compared to the
      growth factor released from fibrin matrices in the absence  of spheres. The
      scaffolds were implanted in a murine critical limb ischemia model at two
      concentrations, 40 ng (low) and 400 ng (high), restoring 92% of the blood flow in
      a normally perfused limb using a fibrin hydrogel releasing FGF-2 containing
      albumin-PLL microspheres releasing G-CSF  (measured by LDPI at the high
      concentration), a 3.2-fold increase compared to untreated limbs. The extent of
      neo-vessel formation was delineated by immunohistochemical staining for capillary
      density (CD-31+) and mature vessel formation (alpha-SMA+). In conclusion, our
      study demonstrated  that the release kinetics from our scaffold have distinct
      kinetics previously unpublished and the delivery of these factors resulted in
      hindlimb reperfusion, and robust capillary and mature vessel formation after 8
      weeks compared to either growth factor alone or bolus administration of growth 
      factor.

PMID- 21192838
TI  - Chitosan, gelatin and poly(L-lysine) polyelectrolyte-based scaffolds and films
      for neural tissue engineering.
AB  - Biomaterial implants are a promising strategy to replace neural tissue that is
      lost after traumatic nerve damage. Chitosan (Ch) is a suitable material for nerve
      implantation when it is used at a minimum amount of 2% (w/v). The goal of this
      study was to determine the best mixture of  2% Ch with gelatin (G) and poly(L
      lysine) (PLL) for use in neural tissue engineering. Using different
      physicochemical approaches we showed that all mixtures formed polyelectrolyte
      complexes with distinct electrostatic interactions between their compounds. This
      gave rise to different gel morphologies,  among which Ch + G exhibited a
      significantly smaller pore size, unlike Ch + G + PLL. However, thermal resistance
      to degradation and the wettability of the Ch-based films were not affected.
      Additionally, these differences affected glial cells growth in long-term (14
      days) cultures performed  on Ch-based films. Astrocytes and olfactory ensheathing
      cells proliferated on G and Ch + G films which induced both flattened and spindle
      cell morphologies. Meanwhile, cortical and hippocampal neurons were similarly
      viable in all studied films and significantly lower than those observed in 
      controls. Lastly, neurites from dorsal root ganglia extended the most on Ch + G
      films. These results show that a Ch + G mixture is a promising candidate for use
      in neural tissue engineering.

PMID- 21192839
TI  - Targeted cancer therapies.
AB  - With unprecedented understanding of molecular events underlying human cancer in
      this genomic era, a large number of drugs specifically targeting hypothesized
      oncogenic drivers to which tumors are potentially addicted to have been developed
      and continue to be developed. These targeted cancer therapies are being actively
      tested in clinical trials with mixed successes. This editorial provides an
      overview on successful targeted cancer drugs on the market and those drugs that
      are in late clinical development stages. Importantly, the article lays out main
      challenges in developing molecular targeted therapies and potential path forward
      to overcome these challenges, as well as opportunities for China in this new era
      of targeted agents. The editorial serves as an introduction to the Targeted
      Cancer Therapies series that will review in depth of major pathways and drugs
      targeting these pathways to be published in the coming issues of the Chinese
      Journal of Cancer.

PMID- 21192840
TI  - Therapeutic targeting of epidermal growth factor receptor in human cancer:
      successes and limitations.
AB  - Epidermal growth factor receptor (EGFR) is one of the most commonly altered genes
      in human cancer by way of over-expression, amplification, and mutation. Targeted
      inhibition of EGFR activity suppresses signal transduction pathways which control
      tumor cell growth, proliferation, and resistance to apoptosis. Small molecule
      tyrosine kinase inhibitors and monoclonal antibodies are among the most common
      EGFR-targeting agents and have been used clinically for treating various
      malignancies. This review discusses the successes and challenges of targeting
      EGFR in human cancer. The genetic alterations of EGFR tend to occur more often in
      some solid tumors than others, as do the mechanisms of resistance to targeted
      inhibition. The clinical and basic science experiences with these agents thus far
      have important implications for the future of therapeutic targeting of EGFR.

PMID- 21192842
TI  - A systems biological approach to identify key transcription factors and their
      genomic neighborhoods in human sarcomas.
AB  - Identification of genetic signatures is the main objective for many computational
      oncology studies. The signature usually consists of numerous genes that are
      differentially expressed between two clinically distinct groups of samples, such
      as tumor subtypes. Prospectively, many signatures have been found to generalize
      poorly to other datasets and, thus, have rarely been accepted into clinical use.
      Recognizing the limited success of traditionally generated signatures, we
      developed a systems biology-based framework for robust identification of key
      transcription factors and their genomic regulatory neighborhoods. Application of
      the framework to study the differences between gastrointestinal stromal tumor
      (GIST) and leiomyosarcoma (LMS) resulted in the identification of nine
      transcription factors (SRF, NKX2-5, CCDC6, LEF1, VDR, ZNF250, TRIM63, MAF, and
      MYC). Functional annotations of the obtained neighborhoods identified the
      biological processes which the key transcription factors regulate differently
      between the tumor types. Analyzing the differences in the expression patterns
      using our approach resulted in a more robust genetic signature and more
      biological insight into the diseases compared to a traditional genetic signature.

PMID- 21192841
TI  - Clinical implications of hedgehog signaling pathway inhibitors.
AB  - Hedgehog was first described in Drosophila melanogaster by the Nobel laureates
      Eric Wieschaus and Christiane Nusslein-Volhard. The hedgehog (Hh) pathway is a
      major regulator of cell differentiation, proliferation, tissue polarity, stem
      cell maintenance, and carcinogenesis. The first link of Hh signaling to cancer
      was established through studies of a rare familial disease, Gorlin syndrome, in
      1996. Follow-up studies revealed activation of this pathway in basal cell
      carcinoma, medulloblastoma and, leukemia as well as in gastrointestinal, lung,
      ovarian, breast, and prostate cancer. Targeted inhibition of Hh signaling is now
      believed to be effective in the treatment and prevention of human cancer. The
      discovery and synthesis of specific inhibitors for this pathway are even more
      exciting. In this review, we summarize major advances in the understanding of Hh
      signaling pathway activation in human cancer, mouse models for studying Hh
      mediated carcinogenesis, the roles of Hh signaling in tumor development and
      metastasis, antagonists for Hh signaling and their clinical implications.

PMID- 21192843
TI  - Apogossypolone targets mitochondria and light enhances its anticancer activity by
      stimulating generation of singlet oxygen and reactive oxygen species.
AB  - Apogossypolone (ApoG2), a novel derivative of gossypol, has been shown to be a
      potent inhibitor of antiapoptotic Bcl-2 family proteins and to have antitumor
      activity in multiple types of cancer cells. Recent reports suggest that gossypol
      stimulates the generation of cellular reactive oxygen species (ROS) in leukemia
      and colorectal carcinoma cells; however, gossypol-mediated cell death in leukemia
      cells was reported to be ROS-independent. This study was conducted to clarify the
      effect of ApoG2-induced ROS on mitochondria and cell viability, and to further
      evaluate its utility as a treatment for nasopharyngeal carcinoma (NPC). We tested
      the photocytotoxicity of ApoG2 to the poorly differentiated NPC cell line CNE-2
      using the ROS-generating TL/10 illumination system. The rapid ApoG2-induced cell
      death was partially reversed by the antioxidant N-acetyl-L-cysteine (NAC), but
      the ApoG2-induced reduction of mitochondrial membrane potential (MMP) was not
      reversed by NAC. In the presence of TL/10 illumination, ApoG2 generated massive
      amounts of singlet oxygen and was more effective in inhibiting cell growth than
      in the absence of illumination. We also determined the influence of light on the
      anti-proliferative activity of ApoG2 using a CNE-2-xenograft mouse model. ApoG2
      under TL/10 illumination healed tumor wounds and suppressed tumor growth more
      effectively than ApoG2 treatment alone. These results indicate that the ApoG2
      induced CNE-2 cell death is partly ROS-dependent. ApoG2 may be used with
      photodynamic therapy (PDT) to treat NPC.

PMID- 21192844
TI  - MUC1-positive circulating tumor cells and MUC1 protein predict chemotherapeutic
      efficacy in the treatment of metastatic breast cancer.
AB  - Chemotherapy plays an important role in the treatment of metastatic breast
      cancer. It is important to monitor chemotherapeutic efficacy, to find a simple
      and efficient tool to guide treatment, and to predict the efficacy of treatment
      in a timely and accurate manner. This study aimed to detect mucin-1 (MUC1)
      positive circulating tumor cells and MUC1 protein in the peripheral blood of
      patients with metastatic breast cancer and to investigate their relationship to
      chemotherapeutic efficacy. MUC1 mRNA was detected in the peripheral blood of 34
      patients with newly diagnosed metastatic breast cancer by reverse transcription
      polymerase chain reaction. The positive rates of MUC1 mRNA were 88.2% before
      chemotherapy and 70.6% after chemotherapy, without a significant difference
      (P=0.564); MUC1 mRNA expression before chemotherapy had no correlation with
      treatment effectiveness (P=0.281). The response rate of MUC1 mRNA-negative
      patients after first-cycle chemotherapy was significantly higher (P=0.009) and
      the progression-free survival (PFS) was clearly longer than those of MUC1 mRNA
      positive patients (P=0.095). MUC1 protein in peripheral blood plasma was detected
      by an ELISA competitive inhibition assay. The patients with decreased MUC1
      protein after chemotherapy had a significantly longer PFS than those with
      elevated MUC1 protein (P=0.044). These results indicate that the outcomes of MUC1
      mRNA-negative patients after chemotherapy are better than those of MUC1 mRNA
      positive patients. In addition, patients with decreased expression of MUC1
      protein have a better PFS.

PMID- 21192845
TI  - Expression and unique functions of four nuclear factor of activated T cells
      isoforms in non-small cell lung cancer.
AB  - Nuclear factor of activated T cells (NFAT) is an important family of
      transcription factors that can be activated by calmodulin and calcineurin in
      human cells. To investigate the expression and clinical significance of NFAT
      isoforms and calcineurin in non-small cell lung cancer (NSCLC), we collected
      tumor and adjacent normal tissues from 159 NSCLC patients and assembled them in a
      tissue microarray. Protein levels of NFAT1, NFAT2, NFAT3, NFAT4, and calcineurin
      were determined using immunohistochemistry. Correlations between NFAT and
      calcineurin expression and clinicopathologic characteristics were analyzed. We
      found that the positive rates of NFAT1 (52.8%, 84/159), NFAT2 (11.3%, 18/159),
      NFAT3 (28.3%, 45/159), NFAT4 (47.2%, 75/159), and calcineurin (47.8%, 76/159)
      expression were significantly higher in tumor tissues than in adjacent normal
      lung tissues (P<0.001), respectively. The positive rate of NFAT1 expression was
      significantly higher in patients with adenocarcinoma (63.5%, 47/74) than in those
      with squamous cell carcinoma (43.5%, 37/85) (chi2=6.340, P=0.012); with lymph
      node metastasis (61.6%, 53/86) than without lymph node metastasis (42.5%, 31/73)
      (chi2=5.818, P=0.016); and with stage-II and -III diseases (61.8%, 55/89) than
      with stage-I disease (41.4%, 29/70) (chi2=6.524, P=0.011). Moreover, the
      overexpression of NFAT1 was associated with poor survival of NSCLC patients
      (chi2=5.006, P=0.025). The positive rate of NFAT4 was significantly higher in
      patients with squamous carcinoma (57.6%, 49/85) than in those with adenocarcinoma
      (35.1%, 26/74) (chi2=8.045, P=0.005) and with high and moderate differentiation
      (54.9%, 61/111) than with low differentiation (29.2%, 14/48) (chi2=8.943,
      P=0.003). Calcineurin overexpression was significantly associated with histologic
      type (higher in squamous carcinoma than in adenocarcinoma, chi2=8.897, P=0.003),
      differentiation grade (higher in high-moderation grade than in low grade,
      chi2=9.566, P=0.002) and gender (higher in male than in female, chi2=5.766,
      P=0.016). Furthermore, calcineurin expression was significantly correlated with
      NFAT4 level (r=0.429, P<0.001). These results suggest that NFAT1 expression is
      associated with lung adenocarcinoma progression, and NFAT4 expression, which was
      higher in squamous lung cancer, is associated with calcineurin expression and
      differentiation grade.

PMID- 21192846
TI  - Expressions of the gamma2 chain of laminin-5 and secreted protein acidic and rich
      in cysteine in esophageal squamous cell carcinoma and their relation to
      prognosis.
AB  - Previous studies have shown that the expressions of the gamma2 chain of laminin-5
      and secreted protein acidic and rich in cysteine (SPARC) play important roles in
      oncogenesis and the development of carcinoma. To assess the expressions of
      laminin-5 gamma2 chain and SPARC in esophageal squamous cell carcinoma (SCC), and
      to clarify the prognostic significance of the expressions of laminin-5 gamma2
      chain and SPARC in esophageal SCC, we detected the expressions of laminin-5
      gamma2 chain and SPARC in cancer tissue and corresponding normal mucosa from 116
      patients with advanced (stages II-IV) esophageal SCC using the tissue microarray
      based immunohistochemistry and analyzed the correlation of the expressions with
      clinicopathologic characteristics and survival. We found that in normal
      esophageal tissues, laminin-5 gamma2 chain was expressed in the basement
      membrane, whereas in esophageal SCC tissues, laminin-5 gamma2 chain was expressed
      in the cytoplasm of carcinoma cells, with a positive rate of 72.4%. SPARC was not
      detected in normal esophageal mucosa, but was expressed in stromal fibroblasts in
      84.6% of esophageal SCC cases and in cancer cells in 7.8% of esophageal SCC
      cases. There was a significant correlation between laminin-5 gamma2 chain and
      stromal SPARC expression in esophageal SCC (Spearman's rho=0.423, P<0.001). The
      expressions of both laminin-5 gamma2 chain and stromal SPARC were correlated with
      survival (P=0.032 and P=0.034, respectively). In stage-II esophageal SCC, the
      expression of laminin-5 gamma2 chain was significantly correlated with survival
      (P=0.023), while the expression of SPARC was not significantly correlated with
      survival (P=0.154). Patients with elevated levels of laminin-5 gamma2 chain and
      SPARC expressions had a poorer prognosis than did those lacking elevated levels
      of laminin-5 gamma2 chain expression and/or elevated levels of SPARC expression
      (P=0.001). In stage-II esophageal SCC, patients with elevated levels of laminin-5
      gamma2 chain and SPARC expressions had a poorer prognosis (P<0.001). These
      results suggest that laminin-5 gamma2 chain and SPARC may play roles in the
      progression of esophageal SCC and their simultaneous expression is correlated
      with poorer prognosis, especially in patients with stage-II SCC.

PMID- 21192847
TI  - Public health implications of cysticercosis acquired in the United States.
AB  - Cysticercosis has emerged as a cause of severe neurologic disease in the United
      States that primarily affects immigrants from Latin America. Moreover, the
      relevance of cysticercosis as a public health problem has been highlighted by
      local transmission. We searched the biomedical literature for reports documenting
      cases of cysticercosis acquired in the United States. A total of 78 cases,
      principally neurocysticercosis, were reported from 12 states during 1954-2005. A
      confirmed or presumptive source of infection was identified among household
      members or close personal contacts of 16 (21%) case-patients. Several factors,
      including the severe, potentially fatal, nature of cysticercosis; its fecal-oral
      route of transmission; the considerable economic effect; the availability of a
      sensitive and specific serologic test for infection by adult Taenia solium
      tapeworms; and the demonstrated ability to find a probable source of infection
      among contacts, all provide a compelling rationale for implementation of public
      health control efforts.

PMID- 21192848
TI  - Foodborne illness acquired in the United States--major pathogens.
AB  - Estimates of foodborne illness can be used to direct food safety policy and
      interventions. We used data from active and passive surveillance and other
      sources to estimate that each year 31 major pathogens acquired in the United
      States caused 9.4 million episodes of foodborne illness (90% credible interval
      [CrI] 6.6-12.7 million), 55,961 hospitalizations (90% CrI 39,534-75,741), and
      1,351 deaths (90% CrI 712-2,268). Most (58%) illnesses were caused by norovirus,
      followed by nontyphoidal Salmonella spp. (11%), Clostridium perfringens (10%),
      and Campylobacter spp. (9%). Leading causes of hospitalization were nontyphoidal
      Salmonella spp. (35%), norovirus (26%), Campylobacter spp. (15%), and Toxoplasma
      gondii (8%). Leading causes of death were nontyphoidal Salmonella spp. (28%), T.
      gondii (24%), Listeria monocytogenes (19%), and norovirus (11%). These estimates
      cannot be compared with prior (1999) estimates to assess trends because different
      methods were used. Additional data and more refined methods can improve future
      estimates.

PMID- 21192849
TI  - Foodborne illness acquired in the United States--unspecified agents.
AB  - Each year, 31 major known pathogens acquired in the United States caused an
      estimated 9.4 million episodes of foodborne illness. Additional episodes of
      illness were caused by unspecified agents, including known agents with
      insufficient data to estimate agent-specific illness, known agents not yet
      recognized as causing foodborne illness, substances known to be in food but of
      unproven pathogenicity, and unknown agents. To estimate these additional
      illnesses, we used data from surveys, hospital records, and death certificates to
      estimate illnesses, hospitalizations, and deaths from acute gastroenteritis and
      subtracted illnesses caused by known gastroenteritis pathogens. If the
      proportions acquired by domestic foodborne transmission were similar to those for
      known gastroenteritis pathogens, then an estimated 38.4 million (90% credible
      interval [CrI] 19.8-61.2 million) episodes of domestically acquired foodborne
      illness were caused by unspecified agents, resulting in 71,878 hospitalizations
      (90% CrI 9,924-157,340) and 1,686 deaths (90% CrI 369-3,338).

PMID- 21192850
TI  - Completeness of communicable disease reporting, North Carolina, USA, 1995-1997
      and 2000-2006.
AB  - Despite widespread use of communicable disease surveillance data to inform public
      health intervention and control measures, the reporting completeness of the
      notifiable disease surveillance system remains incompletely assessed. Therefore,
      we conducted a comprehensive study of reporting completeness with an analysis of
      53 diseases reported by 8 health care systems across North Carolina, USA, during
      1995-1997 and 2000-2006. All patients who were assigned an International
      Classification of Diseases, 9th Revision, Clinical Modification, diagnosis code
      for a state-required reportable communicable disease were matched to surveillance
      records. We used logistic regression techniques to estimate reporting
      completeness by disease, year, and health care system. The completeness of
      reporting varied among the health care systems from 2% to 30% and improved over
      time. Disease-specific reporting completeness proportions ranged from 0% to 82%,
      but were generally low even for diseases with great public health importance and
      opportunity for interventions.

PMID- 21192851
TI  - Hepatitis E virus infection without reactivation in solid-organ transplant
      recipients, France.
AB  - Infections with hepatitis E virus (HEV) in solid-organ transplant recipients can
      lead to chronic hepatitis. However, the incidence of de novo HEV infections after
      transplantation and risk for reactivation in patients with antibodies against HEV
      before transplantation are unknown. Pretransplant prevalence of these antibodies
      in 700 solid-organ transplant recipients at Toulouse University Hospital in
      France was 14.1%. We found no HEV reactivation among patients with antibodies
      against HEV at the first annual checkup or by measuring liver enzyme activities
      and HEV RNA. In contrast, we found 34 locally acquired HEV infections among
      patients with no antibodies against HEV, 47% of whom had a chronic infection,
      resulting in an incidence of 3.2/100 person-years. Independent risk factors for
      HEV infection were an age <52 years at transplantation and receiving a liver
      transplant. Effective prophylactic measures that include those for potential
      zoonotic infections should reduce the risk for HEV transmission in this
      population.

PMID- 21192852
TI  - Concurrent conditions and human listeriosis, England, 1999-2009.
AB  - The epidemiology of listeriosis in England and Wales changed during 2001-2008;
      more patients >=60 years of age had bacteremia than in previous years. To
      investigate these changes, we calculated risk for listeriosis by concurrent
      condition for non-pregnancy-associated listeriosis cases reported to the national
      surveillance system in England during 1999-2009. Conditions occurring with L.
      monocytogenes infection were coded according to the International Classification
      of Diseases, 10th Revision, and compared with appropriate hospital episode
      statistics inpatient denominator data to calculate incidence rates/million
      consultations. Malignancies (especially of the blood), kidney disease, liver
      disease, diabetes, alcoholism, and age >=60 years were associated with an
      increased risk for listeriosis. Physicians should consider a diagnosis of
      listeriosis when treating patients who have concurrent conditions. Providing
      cancer patients, who accounted for one third of cases, with food safety
      information might help limit additional cases.

PMID- 21192853
TI  - Genotyping rotavirus RNA from archived rotavirus-positive rapid test strips.
AB  - Genotyping circulating rotaviruses before and after introduction of rotavirus
      vaccine is useful for evaluating vaccine-associated changes in genotype
      distribution. We determined frequency of rotavirus genotypes among 61 rotavirus
      positive children hospitalized in Israel during the 2005-06 rotavirus season.
      Accurate molecular epidemiologic data were recovered from affinity-concentrated
      rotavirus immobilized in rotavirus-positive bands from air-dried, diagnostic
      rotavirus rapid test strips (dipstick) stored at room temperature from 1 week to
      5 years. G genotypes were identical for 21 paired dipsticks and suspensions,
      whereas dipsticks or suspensions detected an additional G genotype in 2 samples.
      RNA sequences from 7 pairs were identical. Phylogenetic analysis suggested
      previously unreported G2 sublineages and G9 lineages. The ease with which
      dipsticks can be stored at local facilities and transported to central reference
      laboratories can reverse increasing difficulties in obtaining geographically
      representative stool samples and expand surveillance to regions lacking adequate
      laboratory facilities.

PMID- 21192854
TI  - Seroprevalence of African swine fever in Senegal, 2006.
AB  - In Senegal, during 2002-2007, 11 outbreaks of African swine fever (ASF) were
      reported to the World Organisation for Animal Health. Despite this, little was
      known of the epidemiology of ASF in the country. To determine the prevalence of
      ASF in Senegal in 2006, we tested serum specimens collected from a sample of pigs
      in the 3 main pig-farming regions for antibodies to ASF virus using an ELISA. Of
      747 serum samples examined, 126 were positive for ASF, suggesting a prevalence of
      16.9%. The estimated prevalences within each of the regions (Fatick, Kolda, and
      Ziguinchor) were 13.3%, 7.8%, and 22.1%, respectively, with statistical evidence
      to suggest that the prevalence in Ziguinchor was higher than in Fatick or Kolda.
      This regional difference is considered in relation to different farming systems
      and illegal trade with neighboring countries where the infection is endemic.

PMID- 21192855
TI  - Molecular typing of protease-resistant prion protein in transmissible spongiform
      encephalopathies of small ruminants, France, 2002-2009.
AB  - The agent that causes bovine spongiform encephalopathy (BSE) may be infecting
      small ruminants, which could have serious implications for human health. To
      distinguish BSE from scrapie and to examine the molecular characteristics of the
      protease-resistant prion protein (PrP(res)), we used a specifically designed
      Western blot method to test isolates from 648 sheep and 53 goats. During 2002
      2009, classical non-Nor98 transmissible spongiform encephalopathy had been
      confirmed among ~1.7 million small ruminants in France. Five sheep and 2 goats
      that showed a PrP(res) pattern consistent with BSE, or with the CH1641
      experimental scrapie source, were identified. Later, bioassays confirmed
      infection by the BSE agent in 1 of the 2 goats. Western blot testing of the 6
      other isolates showed an additional C-terminally cleaved PrP(res) product, with
      an unglycosylated band at ~14 kDa, similar to that found in the CH1641
      experimental scrapie isolate and different from the BSE isolate.

PMID- 21192856
TI  - Endurance, refuge, and reemergence of dengue virus type 2, Puerto Rico, 1986
      2007.
AB  - To study the evolution of dengue virus (DENV) serotype 2 in Puerto Rico, we
      examined the genetic composition and diversity of 160 DENV-2 genomes obtained
      through 22 consecutive years of sampling. A clade replacement took place in 1994
      1997 during a period of high incidence of autochthonous DENV-2 and frequent,
      short-lived reintroductions of foreign DENV-2. This unique clade replacement was
      complete just before DENV-3 emerged. By temporally and geographically defining
      DENV-2 lineages, we describe a refuge of this virus through 4 years of low genome
      diversity. Our analyses may explain the long-term endurance of DENV-2 despite
      great epidemiologic changes in disease incidence and serotype distribution.

PMID- 21192857
TI  - Tick-borne encephalitis virus in wild rodents in winter, Finland, 2008-2009.
AB  - Rodents might maintain tick-borne encephalitis virus (TBEV) in nature through
      latent persistent infections. During 2 subsequent winters, 2008 and 2009, in
      Finland, we detected RNA of European and Siberian subtypes of TBEV in Microtus
      agrestis and Myodes glareolus voles, respectively. Persistence in rodent
      reservoirs may contribute to virus overwintering.

PMID- 21192858
TI  - Serologic status for pandemic (H1N1) 2009 virus, Taiwan.
AB  - We studied preexisting immunity to pandemic (H1N1) 2009 virus in persons in
      Taiwan. A total of 18 (36%) of 50 elderly adults in Taiwan born before 1935 had
      protective antibodies against currently circulating pandemic (H1N1) 2009 virus.
      Seasonal influenza vaccines induced antibodies that did not protect against
      pandemic (H1N1) 2009 virus.

PMID- 21192860
TI  - Identification of rickettsial infections by using cutaneous swab specimens and
      PCR.
AB  - To determine the usefulness of noninvasive cutaneous swab specimens for detecting
      rickettsiae, we tested skin eschars from 6 guinea pigs and from 9 humans.
      Specimens from eschars in guinea pigs were positive for rickettsiae as long as
      lesions were present. Optimal storage temperature for specimens was 4 degrees C
      for 3 days.

PMID- 21192859
TI  - Serodiagnosis of primary infections with human parvovirus 4, Finland.
AB  - To determine the prevalence of parvovirus 4 infection and its clinical and
      sociodemographic correlations in Finland, we used virus-like particle-based
      serodiagnostic procedures (immunoglobulin [Ig] G, IgM, and IgG avidity) and PCR.
      We found 2 persons with parvovirus 4 primary infection who had mild or
      asymptomatic clinical features among hepatitis C virus-infected injection drug
      users.

PMID- 21192861
TI  - Pandemic (H1N1) 2009 outbreak at camp for children with hematologic and oncologic
      conditions.
AB  - An outbreak of influenza A pandemic (H1N1) 2009 occurred among campers and staff
      at a summer camp attended by children with hematologic and oncologic conditions.
      The overall attack rate was 36% and was highest among children and adolescents
      (43%), persons with cancer (48%), and persons with sickle cell disease (82%).

PMID- 21192862
TI  - Reducing Baylisascaris procyonis roundworm larvae in raccoon latrines.
AB  - Baylisascaris procyonis roundworms, a parasite of raccoons, can infect humans,
      sometimes fatally. Parasite eggs can remain viable in raccoon latrines for years.
      To develop a management technique for parasite eggs, we tested anthelmintic
      baiting. The prevalence of eggs decreased at latrines, and larval infections
      decreased among intermediate hosts, indicating that baiting is effective.

PMID- 21192864
TI  - CTX-M-producing non-Typhi Salmonella spp. isolated from humans, United States.
AB  - CTX-M-type beta-lactamases are increasing among US Enterobacteriaceae isolates.
      Of 2,165 non-Typhi Salmonella isolates submitted in 2007 to the National
      Antimicrobial Resistance Monitoring System, 100 (4.6%) displayed elevated MICs
      (>=2 mg/L) of ceftriaxone or ceftiofur. Three isolates (serotypes Typhimurium,
      Concord, and I 4,5,12:i:-) contained bla(CTX-M-5), bla(CTX-M-15), and bla(CTX-M
      55/57), respectively.

PMID- 21192863
TI  - Serotype distribution and drug resistance in Streptococcus pneumoniae,
      Palestinian Territories.
AB  - To determine antimicrobial drug resistance of Streptococcus pneumoniae serotypes,
      we analyzed isolates from blood cultures of sick children residing in the West
      Bank before initiation of pneumococcal vaccination. Of 120 serotypes isolated,
      50.8%, 73.3%, and 80.8% of the bacteremia cases could have been prevented by
      pneumococcal conjugate vaccines. Serotype 14 was the most drug-resistant serotype
      isolated.

PMID- 21192865
TI  - Emergence of Rickettsia africae, Oceania.
AB  - We detected Rickettsia africae, the agent of African tick-bite fever (ATBF), by
      amplification of fragments of gltA, ompA, and ompB genes from 3 specimens of
      Amblyomma loculosum ticks collected from humans and birds in New Caledonia.
      Clinicians who treat persons in this region should be on alert for ATBF.

PMID- 21192866
TI  - New Delhi metallo-beta-lactamase in Klebsiella pneumoniae and Escherichia coli,
      Canada.
AB  - Multidrug-resistant Klebsiella pneumoniae and Escherichia coli isolates harboring
      New Delhi metallo-beta-lactamase (NDM-1) were isolated from a patient who had
      returned to Canada from India. The NDM-1 gene was found on closely related
      incompatibility group A/C type plasmids. The occurrence of NDM-1 in North America
      is a major public health concern.

PMID- 21192867
TI  - Seasonal influenza A (H1N1) infection in early pregnancy and second trimester
      fetal demise.
AB  - A second trimester fetal demise followed influenza-like illness in early
      pregnancy. Influenza A virus (H1N1) was identified in maternal and fetal tissue,
      confirming transplacental passage. These findings suggested a causal relationship
      between early exposure and fetal demise. Management of future influenza outbreaks
      should include evaluation of products of conception associated with fetal loss.

PMID- 21192868
TI  - Possible interruption of measles virus transmission, Uganda, 2006-2009.
AB  - To determine what measles virus genotype(s) circulated in Uganda after strategic
      interventions aimed at controlling/eliminating measles, we examined samples
      obtained during 2006-2009 and found only genotype B3.1, which had not been
      previously detected. Kenya was the likely source, but other countries cannot be
      excluded.

PMID- 21192869
TI  - Babesiosis in immunocompetent patients, Europe.
AB  - We report 2 cases of babesiosis in immunocompetent patients in France. A severe
      influenza-like disease developed in both patients 2 weeks after they had been
      bitten by ticks. Diagnosis was obtained from blood smears, and Babesia divergens
      was identified by PCR in 1 case. Babesiosis in Europe occurs in healthy patients,
      not only in splenectomized patients.

PMID- 21192870
TI  - Echinostoma revolutum infection in children, Pursat Province, Cambodia.
AB  - To determine the prevalence of helminthic infections in Pursat Province,
      Cambodia, we tested fecal specimens from 471 children, 10-14 years of age, in
      June 2007. The prevalence of infection with echinostome flukes ranged from 7.5%
      to 22.4% in 4 schools surveyed. Adult worms were identified as Echinostoma
      revolutum.

PMID- 21192871
TI  - Streptococcus pneumoniae in urinary tracts of children with chronic kidney
      disease.
AB  - Streptococcus pneumoniae is not commonly considered an agent of urinary tract
      infections. We report 3 children with urinary tract abnormalities who had high
      numbers of S. pneumoniae in their urine (>=104 CFU/mL) and varying clinical
      symptoms.

PMID- 21192872
TI  - Foreign travel and decreased ciprofloxacin susceptibility in Salmonella enterica
      infections.
AB  - To determine antimicrobial drug resistance patterns, we characterized
      nontyphoidal Salmonella enterica strains isolated in Liverpool, UK, January 2003
      through December 2009. Decreased susceptibility to ciprofloxacin was found in 103
      (20.9%) of 492 isolates. The lower susceptibility was associated with
      ciprofloxacin treatment failures and with particular serovars and phage types
      often acquired during foreign travel.

PMID- 21192873
TI  - How safe is our food?

PMID- 21192874
TI  - Emergence of New Delhi metallo-beta-lactamase, Austria.

PMID- 21192875
TI  - Carbapenemases in enterobacteria, Hong Kong, China, 2009.

PMID- 21192877
TI  - Apophysomyces variabilis infections in humans.

PMID- 21192876
TI  - Change in age pattern of persons with dengue, northeastern Brazil.

PMID- 21192878
TI  - Fatal Vibrio vulnificus infection associated with eating raw oysters, New
      Caledonia.

PMID- 21192880
TI  - Empyema caused by MRSA ST398 with atypical resistance profile, Spain.

PMID- 21192881
TI  - Intensive care unit admission for pandemic (H1N1) 2009, Reunion Island, 2009.

PMID- 21192882
TI  - Crimean-Congo hemorrhagic fever virus, northeastern Greece.

PMID- 21192883
TI  - Class D OXA-48 carbapenemase in multidrug-resistant enterobacteria, Senegal.

PMID- 21192884
TI  - Identification of Legionella feeleii cellulitis.

PMID- 21192885
TI  - Sparganosis, Henan Province, central China.

PMID- 21192886
TI  - Ceftriaxone-resistant Neisseria gonorrhoeae, Japan.

PMID- 21192887
TI  - Role of National Travel Health Network and Centre website during pandemic (H1N1)
      2009.

PMID- 21192888
TI  - Zoonotic cryptosporidiosis from petting farms, England and Wales, 1992-2009.

PMID- 21192889
TI  - Buruli ulcer prevalence and altitude, Benin.

PMID- 21192890
TI  - Vibrio cholerae O1 in 2 coastal villages, Papua New Guinea.

PMID- 21192891
TI  - Clostridium sphenoides bloodstream infection in man.

PMID- 21192892
TI  - Manna to gall.

PMID- 21192893
TI  - [Obtaining corneas by donation].
AB  - The cadaveric donation is not a programmed event. In the critical areas where
      exist a potential donating patient of organs and tissues initiate a cascade of
      actions in which medical, legal and social aspects are involved. The Program of
      Obtaining-Transplant organs and tissues began in 2004 with the creation of the
      Department of Coordination Donation for the training of personnel to lead this
      process. The diffusion of strategies used in these processes is the aim of this
      publication, as well as to describe the current difficulties to achieve an
      improvement in donation according to needs.

PMID- 21192894
TI  - [The perinatal mortality in a general hospital].
AB  - BACKGROUND: the perinatal mortality (PM) represents a partial expression of a
      developing country and its health programs. The aim was to determine the rate of
      PM in a second level hospital that lacks the support of a perinatal care unit,
      and to help with some epidemiological elements to plan strategies to give a
      better care in the perinatal stage. METHODS: we collected all records of deaths
      within the parameters of perinatal death. DATA INCLUDED: maternal age, prenatal
      history, cause of the perinatal death and birth control information. RESULTS: out
      of 117 deaths, 59.8 % were in the late fetal death stage, and the rest in the
      first week of life. The PM rate calculated for each year from 2004 to 2007 was
      the following: 11.3, 12.8, 12.53, and 15.46: The birth control was good in 73 %
      of the cases, the most frequent cause of death was the interruption of maternal
      fetal circulation in 80 % of the cases, and the early neonatal death was due to
      perinatal asphyxia in 20 %. The incidence of major malformations was 26.5 %.
      CONCLUSIONS: the undeniable increase in the PM rate forced us to encourage our
      staff to improve the availability of adequate material for the neonatal care.

PMID- 21192895
TI  - [Quality indicators in the early detection of cervicouterine-cancer in primary
      health care units].
AB  - BACKGROUND: to determine the quality of a prompt cervical cancer detection
      program (TDC CC) according to the indicators for prevention and diagnosis.
      METHODS: cross-sectional and comparative study conducted in four primary care
      units. We selected 400 patients who attended preventive services to participate
      in the study of cervical cytology (Pap). The evaluation of the Program of TDC CC
      was obtained by the degree of fulfillment of quality and productivity outlined by
      an institutional program. The seven indicators were measured by the same scale. A
      descriptive statistics, adjusted kappa, and chi square with a level of
      significance of 95 % confidence interval was used. RESULTS: the average age was
      40 +/- 12.6 years. Most women (92.5 %) had information about the Pap screening
      method in CC, even thought only 25.3 % had this test done in the last three
      years. The inter-observer agreement was scored low by three cytotechnologists.
      The degree of compliance according to indicators of the 4 units was 35.7 %, and
      was rated as moderate. The best indicators were great productivity among
      cytotechnologists, the number and proportion of re-examined cytologies.
      CONCLUSIONS: most indicators were below the expected values.

PMID- 21192896
TI  - [Epidemiological pattern of breast cancer mortality in Mexico State].
AB  - BACKGROUND: breast cancer (BC) is the leading cause of death secondary to
      malignancy in women. It ranks third in mortality in women in reproductive age,
      produced by non-modifiable (genetic and hormonal) and modifiable factors. Our
      objective was to describe and analyze the epidemiological characteristics of
      deaths from BC in the State of Mexico. RESULTS: of 273 verbal autopsies, the most
      common age (23.07 %) was between 40 and 49 years. The educational level of
      schooling were complete elementary school (20.51 %), incomplete elementary school
      (19.04 %) and complete high school (13.91 %). the institution with the highest
      number of patients was the Instituto Mexicano del Seguro Social with 139 (50.91
      %). The towns with a higher frequency were Malinalco, Ayapango, Atizapan,
      Zacualpan and Apaxco. The Mortality was higher in Valle de Bravo, Coatepec
      Harinas and Toluca. CONCLUSIONS: the increase in BC has permitted the emergence
      of a new hypothesis known as endocrine disruption, according to this premise,
      this results from exposure to chemicals introduced into the environment by human
      activity capable of altering the hormonal balance.

PMID- 21192897
TI  - [Risk stratified in the National Registry of Acute Coronary Syndromes at the
      IMSS].
AB  - OBJECTIVE: to identify prognostic factors in the National Registry of Acute
      Coronary Syndromes. METHODS: patients in medical care units with acute ischemic
      coronary syndrome (AICS) according to the criteria of the American Heart
      Association/American College of Cardiology/European Society of Cardiology,
      considering the GRACE score (GS) were studied. RESULTS: there were 2389 patients,
      28.9 % women and 71.1 % men, mean age 63 +/- 11.7 years; with AICS with ST
      segment elevation (69.11 %) and 30.89 % with AICS without ST elevation. The
      average of GS was 168. A GS > 150 points in patients with AICS without ST
      elevation was associated with recurrent ischemia or angina (RR = 1.4, p = 0.05),
      left ventricular failure (RR = 3.1, p < 0.0001), stroke (RR = 2.9, p = 0.004) and
      arrhythmias (RR = 2.7, p < 0.0001). The patients with AICS with ST-segment
      elevation were associated with death (RR = 1.6, p = 0.01), reinfarction (RR =
      1.7, p = 0.001), recurrent ischemia (RR = 1.2, p = 0.04), left ventricular
      failure (RR = 3.4, p < 0.001), stroke (RR = 3.9, p < 0.001) and arrhythmias (RR =
      2.3, p < 0.001). Fibrinolytic therapy was used in 40.2 %. There was a negative
      correlation between GS and fibrinolytic therapy (r -0.04, p = 0.04). CONCLUSIONS:
      the AICS with ST-segment elevation is more frequent and have a high GS.

PMID- 21192898
TI  - [Good and bad times of Mexican Hospitals towards 1910].
AB  - This paper presents the situation of the Mexican hospitals from 1910 to 1920,
      times of the Mexican Revolution at that time the country had 15 million
      inhabitants. After the Revolution there were 14 million, the reduction
      casualities caused deaths by the armed movement, infected-contagious diseases and
      hunger. In the previous years to the Revolution during the government of Porfirio
      Diaz, Mexico had public hospitals (originated in the vice-royalty), non profit
      hospitals, private hospitals, military hospitals, for the railroad workers, and
      hospitals for miners. In the last period of the government of Porfirio Diaz
      public hospitals, "pavillon" type were constructed. During the Revolution were
      war hospitals created or fortified the emergency services. In 1920 the great
      majority of the hospitals in Mexico worked deficiently.

PMID- 21192899
TI  - [Hospitals in the New Spain during the Independence war].
AB  - In 1810 Mexico had more than a hundred hospitals scattered throughout its wide
      territory. Some buildings were big with the possibility to accept 600 patients or
      more, and some very small, as those seen in Arizpe, Sonora, or the small missions
      in Michoacan or la Sierra Gorda where only three or four patients could be
      placed. Their origins were diverse; some of them were founded by eminent or pious
      men like Cortes, Zumarraga, Pedro Lopez, Nunez de Haro or Alcalde; others by
      religious orders and laboral guilds, some were only for the military. All of them
      knew good and bad eras, and being the year 1810 bad one. The political and
      economical crisis, derived from the Napoleonic wars and the invasion of Spain and
      the Independence war in Mexico affected strongly the hospitals management and
      function. Also the changes in medical science development and patients attention
      made most of them outdated.

PMID- 21192900
TI  - [Parkinsonism: alternative diagnosis beyond idiopathic Parkinson's disease].
AB  - Parkinsonism is manifested as bradykinesia; tremor with signs and symptoms
      suggesting Parkinson's disease. The most common cause of Parkinsonism is
      Idiopathic Parkinson's disease; however, there are other multiple pathologies and
      situation that have top be considered accordingly in this clinical setting. Since
      the treatment and outcomes varies widely between these conditions is of paramount
      importance to work up the Parkinsonism and try to achieve an accurate diagnosis.
      This review gives a general landscape of Parkinsonism and its most likely
      differentials.

PMID- 21192901
TI  - [A useful guide for selecting pharmacotherapy in type 2 diabetes].
AB  - As the knowledge in medical science development, new molecular mechanism in the
      diabetes had lead to new drugs and therapeutics, althought the change in life
      style of the patient is essential for controling the blood levels in diabetic
      patient glucose. Antidiabetic drugs act through different mechanisms of action,
      including stimulation of insulin secretion, increasing sensitivity to insulin and
      the insulin analogues. Other agents are inhibitors of glucose, and finally drugs
      which imitate intestinal hormones. It is important to emphasize that diabetes is
      better controlled with more than one single drug, however the corner stone of the
      treatment is a correct diet and exercise.

PMID- 21192902
TI  - [Metabolic syndrome in health care personnel from a primary care unit].
AB  - BACKGROUND: the metabolic syndrome (MS) is a public health problem in Mexico and
      in the world due to its progressive growing and cardiovascular complications. Our
      aim was to identify the frequency of MS in health care workers in a primary care
      unit. METHODS: a prospective study, descriptive, observational and transversal
      was performed. A non probabilistic sample was obtained in agreement with health
      90 workers (family physicians, dentist, office medical assistants, nurses,
      laboratory personnel and social workers), that were working from March to
      September of 2007. The Adult Treatment Panel III criterion was used to diagnose
      and classify. RESULTS: the 40 % presented MS, it was higher in women (42 %) and
      in the group of 40 to 49 years (47 %). Dentists and social workers were the most
      affected (62 %), the nurses (42 %), family physicians (32 %) and medical office
      assistant (30 %). CONCLUSIONS: the MS was common in the health personnel. Our
      results showed major frequency compared with that reported in other countries and
      general Mexican population of adults.

PMID- 21192903
TI  - [Cost-effectiveness of anxiolytics in anxiety disorders].
AB  - BACKGROUND: adequate treatment of anxiety disorders reduces the economic impact,
      improves functionality in daily life activities and quality of life.
      Pharmacologic treatment depends on patient's characteristics and doctor's
      experience. The aim of this study was to determine the use of resources in
      anxiety disorder and to analyze its cost-effectiveness. METHODS: use of resources
      related to chronic treatment of anxiety disorders and cost-effectiveness of drugs
      were determined, as well as patients' out-of-pocket expenses and productivity
      loss. A one-year time horizon and decision tree with benzodiazepines, selective
      inhibitor of serotonin re-intake (SISR) and tricyclic antidepressant drugs were
      included. RESULTS: benzodiazepines were the treatment that had the lowest total
      cost ($147,587 MXP), followed by SISR (incremental cost of $2,182 MXP), and the
      highest cost was tricyclic antidepressant drugs ($155,903 MXP). CONCLUSIONS:
      benzodiazepines are good alternative for anxiety disorder because of their high
      effectiveness to control symptoms and because they reduce hospital costs.

PMID- 21192904
TI  - [Keratoconus and corneal transplant clinical study].
AB  - OBJECTIVE: to determine the frequency and clinical characteristics of patients
      with keratoconus and a corneal transplant (CT) at an ophthalmology reference
      hospital. METHODS: retrospective, cross-sectional, observational, descriptive
      study of 166 patients with diagnosis of keratoconus and CT. RESULTS: average age
      of 37.59 years, 97 males (58.43%), 69 females (41.56%). The primarily affected
      eye was the left one (95 cases, 57 %). Coef C -0.01265. The age at the
      keratoconus diagnosis was between 20 and 29 years (77 cases, 46.40 %), with an
      average of 24.5 years. The most frequent signs and symptoms were blurred vision:
      140 (84.33 %), itching: 100 (60.24 %), photophobia: 20 (12.04 %). Associated
      systemic diseases: Down Syndrome 2 cases, (1.20 %), asthma 6 cases (3.61 %),
      atopic dermatitis 14 cases (8.43 %), allergic rhinitis 10 cases (6.02 %). Related
      ocular diseases: allergic conjunctivitis 72 cases (43.47 %). CONCLUSIONS: There
      is strong association between the corneal microtrauma secondary to itching
      resulting from allergic processes and keratoconus. A timely diagnosis is of great
      importance to diminish the progression to corneal scarring requiring a CT.

PMID- 21192905
TI  - [Photodynamic therapy with verteporfirin in corneal neovascularization].
AB  - OBJECTIVE: to evaluate vascular involution of corneal neovessels followed by the
      application of photodynamic therapy (PDT) verteporfirina. METHODS: Prospective,
      longitudinal, case series. Fifty eyes of 49 candidate patients to partial
      penetrating keratoplasty (PPK) also called corneal transplant (CT) at risk of
      corneal neovascularization (CN) of two or more quadrants and which were previous
      treated with intravenous PDT. The monitoring was carried out with photographic
      control of the anterior segment assessing adverse effects and development of CN.
      RESULTS: The length of the CN before and after PDT were 4.39 +/- 2.24 vs 3.71 +/-
      2.48 (p < 0.0001) respectively. This involution was maintained after two months
      of follow up. One eye (2 %) presented changes Keratometry (keratometric
      astigmatism). Of the total 45 (90 %) of patients who showed a reduction in the
      CN, had revascularization within the following six months of intervention.
      CONCLUSIONS: the PDT with verteporfirina is effective and safe for decreasing the
      length of the CN, without local and systemic adverse effects. However it is
      suggested to schedule the surgery two months after to permit revascularization.

PMID- 21192906
TI  - [Two cases of Werdnig-Hofmann disease].
AB  - Spinal muscular atrophy (SMA) is an autonomic recessive disorder that affects the
      anterior horn cells of the spinal cord, degeneration of which results in proximal
      muscle weakness. It is classified into three types: I and II (Werdnig-Hoffmann
      disease) and III (Kugelberg-Welander disease). With an incidence of 1/10,000. We
      report two cases of infants with hypotonic syndrome, that were diagnose with SMA,
      in the first case by muscular biopsy, and in the second by electromyography and
      chromosomes study. It is import that the physicians know about this disease, and
      its complications.

PMID- 21192907
TI  - [Orbital emphysema due to perfluoropropane gas anesthesia in retinal surgery. A
      case report].
AB  - A 45 year old male was referred by the increasing volume of upper and lower
      eyelids with lost vision of his right eye after surgical procedure for recurrent
      retinal detachment. The surgery performed was a scleral buckle, vitrectomy and
      application of perfluoropropane gas to right eye. Ophthalmic examination: visual
      acuity of the right eye showed counting fingers 2 meters, soft tissue crepitating
      and proptosis. Anterior subconjuntival segment was infiltrated by gas, with
      normal intraocular pressure. CT scan shows gas in soft tissues. Because we did
      not find change in the intraocular pressure or damage to the optic nerve we did
      not propose surgical treatment. We managed conservatively considering that this
      gas tends to reabsorp totally as it occurred.

PMID- 21192908
TI  - [The third dimension tomography versus cranial X-ray cephalometry to predict
      maxilla advance by distraction in hypoplastic maxilla].
AB  - BACKGROUND: the osteogenic distraction is the treatment for the correction of the
      hypoplastic maxilla secondary to the repair of a cleft lip-palate. Its planning
      is based on articulated models. Our objective was to describe the accuracy of
      three-dimensional Cephalometry (CT3D) for projecting jaw displacement. METHODS:
      three patients with hypoplastic maxilla. Interventions estimation of the advance
      required of lateral maxilla through Cephalometry of skull (CLC), CT3D and an
      articulated model (gold standard). Two months after distraction finalized the
      advance predicted was compared. RESULTS: the error of the advance projection in
      each patient was smaller with the CT3D versus CLC (+1, +1 and +1 mm versus -10, 
      14 and -9mm). Corrections post-distraction were of +25 %, +26 % and +38.4 % on
      the programmed one. CT3D predicted better the correction (+19 %, +10.8 %, +33.4 %
      versus CLC: -50 %; -60.8 % and -34.6 %). Chewing alterations were not seen in any
      patient. CONCLUSIONS: the planning of the necessary advance for distraction in
      patients with hypoplastic maxilla by CT3D can shorten the time of studies and
      should be consider as next to the projection of articulated model.

PMID- 21192909
TI  - [Necrotizing scleritis and recurrent erythema nodosum: a diagnostic challenge].
AB  - The necrotizing scleritis and recurrent erythema nodosum, two clinical entities
      difficult to diagnose and which represent a challenge to the physician.
      Tuberculosis produces both processes by an immune reaction of delayed
      hypersensitivity type IV to various antigenic components of mycobacteria. Most
      tuberculosis patients have no ocular history of pulmonary or systemic disease in
      up to 50 % and no evidence of pathology in the chest radiograph. An adequate
      treatment leads to a favorable prognosis. It occurs when the diagnosis of
      infection is made on time. We describe the case of a woman with necrotizing
      scleritis associated with recurrent erythema nodosum secondary to infection with
      Mycobacterium tuberculosis complex.

PMID- 21192910
TI  - [The "empacho" from the academic medicine. Commentaries from a reader].

PMID- 21192912
TI  - [Influence of Instituto Mexicano de Seguro Social in the general mortality (1990
      2005)].
AB  - The epidemiologic transition moves mortality towards the chronic diseases as the
      main causes and the elderly groups as their main targets. The Institute Mexican
      del Seguro Social (IMSS) contributes with 3 of every 10 deaths reported in the
      country. Mortality rates in men increased from 330.1 x 100,000 in 1990 to 485.4
      in 2005. In women rates grew from 249.9 to 405.5 in the same period. Mortality
      patterns show a mayor contribution by the northern region and are different with
      regard to sex and age groups. The group under 20 years old have a lower
      contribution to mortality during the period studied. In the population insured by
      IMSS, the 60 to 79 age group in both sexes contributes with a major proportion of
      deaths.

PMID- 21192913
TI  - Quantitative analysis of tissue folate using ultra high-performance liquid
      chromatography tandem mass spectrometry.
AB  - The tissue distribution of folate in its numerous coenzyme forms may influence
      the development of disease at different sites. For instance, the susceptibility
      of human colonic mucosa to localized folate deficiency may predispose to the
      development of colorectal cancer. We report a sensitive and robust ultra high
      performance liquid chromatography (UHPLC) tandem mass spectrometry method for
      quantifying tissue H(4)folate, 5-CH(3)-H(4)folate, 5-CHO-H(4)folate, folic acid,
      and 5,10-CH(+)-H(4)folate concentration. Human colonic mucosa (20-100mg) was
      extracted using lipase and conjugase enzyme digestion. Rapid separation of
      analytes was achieved on a UHPLC 1.9-MUm C18 column over 7 min. Accurate
      quantitation was performed using stable isotopically labeled ((13)C(5)) internal
      standards. The instrument response was linear over physiological concentrations
      of tissue folate (R(2)>0.99). Limits of detection and quantitation were less than
      20 and 30 fmol on column, respectively, and within- and between-run imprecision
      values were 6-16%. In colonic mucosal samples from 73 individuals, the average
      molar distribution of folate coenzymes was 58% 5-CH(3)-H(4)folate, 20%
      H(4)folate, 18% formyl-H(4)folate (sum of 5-CHO-H(4)folate and 5,10-CH(+)
      H(4)folate), and 4% folic acid. This assay would be useful in characterizing
      folate distribution in human and animal tissues as well as the role of
      deregulated folate homeostasis on disease pathogenesis.

PMID- 21192914
TI  - Stimulation of mechano-growth factor expression by second messengers.
AB  - The effect of second messengers on the expression of mechano-growth factor (MGF)
      synthesis by myoblasts and differentiated myotubes in culture was investigated.
      cAMP stimulates MGF expression both in murine and human cells. CNG- and HCN
      channel blockers slightly activated MGF synthesis, while an activator of Epac
      protein had no effect. It is assumed that cAMP activates MGF synthesis via
      protein kinase A. Phorbol ester (PMA) activates MGF synthesis in human myoblasts
      and myotubes only. The expression of another splice form of IGF-1 gene, IGF-1Ea,
      was also stimulated in human cells by db-cAMP and PMA and in murine cells by db
      cAMP only. Stimulation of MGF expression in human cells by db-cAMP and PMA
      demonstrated different time dependences but showed additivity when the compounds
      were applied in a combination. Inhibitors specific to protein kinase A did not
      affect PMA-mediated activation, while inhibitors specific to protein kinase C did
      not affect db-cAMP-mediated process. Ca2+ ionophore and ROS inductor strongly
      inhibited synthesis of the growth factor. PGE2 known as physiological stimulator
      of cAMP synthesis was shown to stimulate MGF expression both in murine and human
      cells. Implication of protein kinase A and protein kinase C in MGF synthesis
      stimulation and a cross-talk between two signaling systems is discussed.

PMID- 21192915
TI  - Structure and dynamics of the lipid modifications of a transmembrane alpha
      helical peptide determined by 2H solid-state NMR spectroscopy.
AB  - The fusion of biological membranes is mediated by integral membrane proteins with
      alpha-helical transmembrane segments. Additionally, those proteins are often
      modified by the covalent attachment of hydrocarbon chains. Previously, a series
      of de novo designed alpha-helical peptides with mixed Leu/Val sequences was
      presented, mimicking fusiogenically active transmembrane segments in model
      membranes (Hofmann et al., Proc. Natl. Acad. Sci. USA 101 (2004) 14776-14781).
      From this series, we have investigated the peptide LV16 (KKKW LVLV LVLV LVLV LVLV
      KKK), which was synthesized featuring either a free N-terminus or a saturated N
      acylation of 2, 8, 12, or 16 carbons. We used 2H and 31P NMR spectroscopy to
      investigate the structure and dynamics of those peptide lipid modifications in
      POPC and DLPC bilayers and compared them to the hydrocarbon chains of the
      surrounding membrane. Except for the C2 chain, all peptide acyl chains were found
      to insert well into the membrane. This can be explained by the high local lipid
      concentrations the N-terminal lipid chains experience. Further, the insertion of
      these peptides did not influence the membrane structure and dynamics as seen from
      the 2H and 31P NMR data. In spite of the fact that the longer acyl chains insert
      into the membrane, they do not adapt their lengths to the thickness of the
      bilayer. Even the C16 lipid chain on the peptide, which could match the length of
      the POPC palmitoyl chain, exhibited lower order parameters in the upper chain,
      which get closer and finally reach similar values in the lower chain region. 2H
      NMR square law plots reveal motions of slightly larger amplitudes for the peptide
      lipid chains compared to the surrounding phospholipids. In spite of the
      significantly different chain lengths of the acylations, the fraction of gauche
      defects in the inserted chains is constant.

PMID- 21192916
TI  - Membrane selectivity by W-tagging of antimicrobial peptides.
AB  - A pronounced membrane selectivity is demonstrated for short, hydrophilic, and
      highly charged antimicrobial peptides, end-tagged with aromatic amino acid
      stretches. The mechanisms underlying this were investigated by a method
      combination of fluorescence and CD spectroscopy, ellipsometry, and Langmuir
      balance measurements, as well as with functional assays on cell toxicity and
      antimicrobial effects. End-tagging with oligotryptophan promotes peptide-induced
      lysis of phospholipid liposomes, as well as membrane rupture and killing of
      bacteria and fungi. This antimicrobial potency is accompanied by limited toxicity
      for human epithelial cells and low hemolysis. The functional selectivity
      displayed correlates to a pronounced selectivity of such peptides for anionic
      lipid membranes, combined with a markedly reduced membrane activity in the
      presence of cholesterol. As exemplified for GRR10W4N (GRRPRPRPRPWWWW-NH(2)),
      potent liposome rupture occurs for anionic lipid systems
      (dioleoylphosphatidylethanolamine (DOPE)/dioleoylphosphatidylglycerol (DOPG) and
      Escherichia coli lipid extract) while that of zwitterionic
      dioleoylphosphatidylcholine (DOPC)/cholesterol is largely absent under the
      conditions investigated. This pronounced membrane selectivity is due to both a
      lower peptide binding to the zwitterionic membranes (z~-8-10mV) than to the
      anionic ones (z~-35-40mV), and a lower degree of membrane incorporation in the
      zwitterionic membranes, particularly in the presence of cholesterol. Replacing
      cholesterol with ergosterol, thus mimicking fungal membranes, results in an
      increased sensitivity for peptide-induced lysis, in analogy to the antifungal
      properties of such peptides. Finally, the generality of the high membrane
      selectivity for other peptides of this type is demonstrated.

PMID- 21192918
TI  - How vision is shaped by language comprehension--top-down feedback based on low
      spatial frequencies.
AB  - Effects of language comprehension on visual processing have been extensively
      studied within the embodied-language framework. However, it is unknown whether
      these effects are caused by passive repetition suppression in visual processing
      areas, or depend on active feedback, based on partial input, from prefrontal
      regions. Based on a model of top-down feedback during visual recognition, we
      predicted diminished effects when low-spatial frequencies were removed from
      targets. We compared low-pass and high-pass filtered pictures in a sentence
      picture-verification task. Target pictures matched or mismatched the implied
      shape of an object mentioned in a preceding sentence, or were unrelated to the
      sentences. As predicted, there was a large match advantage when the targets
      contained low-spatial frequencies, but no effect of linguistic context when these
      frequencies were filtered out. The proposed top-down feedback model is superior
      to repetition suppression in explaining the current results, as well as earlier
      results about the lateralization of this effect, and peculiar color match
      effects. We discuss these findings in the context of recent general proposals of
      prediction and top-down feedback.

PMID- 21192917
TI  - The immiscible cholesterol bilayer domain exists as an integral part of
      phospholipid bilayer membranes.
AB  - Electron paramagnetic resonance (EPR) spin-labeling methods were used to study
      the organization of cholesterol and phospholipids in membranes formed from
      Chol/POPS (cholesterol/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylserine)
      mixtures, with mixing ratios from 0 to 3. It was confirmed using the
      discrimination by oxygen transport and polar relaxation agent accessibility
      methods that the immiscible cholesterol bilayer domain (CBD) was present in all
      of the suspensions when the mixing ratio exceeded the cholesterol solubility
      threshold (CST) in the POPS membrane. The behavior of phospholipid molecules was
      monitored with phospholipid analogue spin labels (n-PCs), and the behavior of
      cholesterol was monitored with the cholesterol analogue spin labels CSL and ASL.
      Results indicated that phospholipid and cholesterol mixtures can form a membrane
      suspension up to a mixing ratio of ~2. Additionally, EPR spectra for n-PC, ASL,
      and CSL indicated that both phospholipids and cholesterol exist in these
      suspensions in the lipid-bilayer-like structures. EPR spectral characteristics of
      n-PCs (spin labels located in the phospholipid cholesterol bilayer, outside the
      CBD) change with increase in the cholesterol content up to and beyond the CST.
      These results present strong evidence that the CBD forms an integral part of the
      phospholipid bilayer when formed from a Chol/POPS mixture up to a mixing ratio of
      ~2. Interestingly, CSL in cholesterol alone (without phospholipids) when
      suspended in buffer does not detect formation of bilayer-like structures. A
      broad, single-line EPR signal is given, similar to that obtained for the dry film
      of cholesterol before addition of the buffer. This broad, single-line signal is
      also observed in suspensions formed for Chol/POPS mixtures (as a background
      signal) when the Chol/POPS ratio is much greater than 3. It is suggested that the
      EPR spin-labeling approach can discriminate and characterize the fraction of
      cholesterol that forms the CBD within the phospholipid bilayer.

PMID- 21192919
TI  - PPARdelta deficient mice develop elevated Th1/Th17 responses and prolonged
      experimental autoimmune encephalomyelitis.
AB  - Multiple sclerosis (MS) is a neurological disorder that affects more than a
      million people worldwide. The etiology of MS is not known and there is no medical
      treatment that can cure MS. Earlier studies have shown that peroxisome
      proliferator-activated receptor (PPARs) agonists ameliorate MS-like disease in
      experimental allergic encephalomyelitis (EAE). In this study we have used
      PPARdelta deficient mice to determine its physiological role in the regulation of
      CNS EAE and MS. We found that PPARdelta(-/-) mice develop EAE with similar day of
      onset and disease incidence compared to C57BL/6 wild type mice. Interestingly,
      both male and female PPARdelta(-/-) mice showed prolonged EAE with resistance to
      remission and recovery. PPARdelta(-/-) mice with EAE expressed elevated levels of
      IFNgamma and IL-17 along with IL-12p35 and IL-12p40 in the brain and spleen.
      PPARdelta(-/-) mice also developed augmented neural antigen-specific Th1/Th17
      responses and impaired Th2/Treg responses compared to wild type mice. These
      findings indicate that PPARdelta(-/-) mice develop prolonged EAE in association
      with augmented Th1/Th17 responses, suggesting a critical physiological role for
      PPARdelta in the remission and recovery of EAE.

PMID- 21192920
TI  - Distribution patterns of cannabinoid CB1 receptors in the hippocampus of
      APPswe/PS1DeltaE9 double transgenic mice.
AB  - Cannabinoids have neuroprotective effects that are exerted primarily through
      cannabinoid CB1 receptors in the brain. This study characterized CB1 receptor
      distribution in the double transgenic (dtg) APP(swe)/PS1(DeltaE9) mouse model for
      Alzheimer's disease. Immunohistochemical labeling of CB1 protein in non
      transgenic mice revealed that CB1 was highly expressed in the hippocampus, with
      the greatest density of CB1 protein observed in the combined hippocampal
      subregions CA2 and CA3 (CA2/3). CB1 immunoreactivity in the CA1 and CA2/3
      hippocampal regions was significantly decreased in the dtg APP(swe)/PS1(DeltaE9)
      mice compared to non-transgenic littermates. Reduced CB1 expression in dtg
      APP(swe)/PS1(DeltaE9) mice was associated with astroglial proliferation and
      elevated expression of the cytokines inducible nitric oxide synthase and tumor
      necrosis factor alpha. This finding suggests an anti-inflammatory effect of
      cannabinoids that is mediated by CB1 receptor, particularly in the CA2/3 region
      of the hippocampus. Furthermore, the study suggests a decreased CB1 receptor
      expression may result in diminished anti-inflammatory processes, exacerbating the
      neuropathology associated with Alzheimer's disease.

PMID- 21192921
TI  - Control of MCT1 function in cerebrovascular endothelial cells by intracellular
      pH.
AB  - Monocarboxylic Acid Transporter 1 (MCT1) is expressed on the plasma membrane of
      cerebrovascular endothelial cells where it is the only known facilitator of
      lactic acid transport across the blood brain barrier. During stroke, brain
      injury, and certain other brain pathologies, anaerobic glycolysis produces severe
      lactic acidosis of brain tissue leading to brain cell damage. Therefore, a better
      understanding of factors that control MCT1 function may be the key to better
      understanding the origins and treatment of pathological lactic acidosis. In this
      study, we characterized the effects of intracellular pH in controlling MCT1
      function and showed that microtubule disruption targeted this mechanism in rat
      cerebrovascular endothelial cells. Acidic intracellular pH values were shown to
      strongly inhibit lactic acid transport into the cytoplasmic space, while
      alkalinization of the cytoplasm significantly enhanced this transport function.
      These results support a better understanding of how cerebrovascular endothelial
      MCT1 may contribute to the development of lactic acidosis in brain pathologies,
      and suggest targeting it as a novel therapy.

PMID- 21192922
TI  - 6-O-Angeloylenolin induced cell-cycle arrest and apoptosis in human
      nasopharyngeal cancer cells.
AB  - High incidence of lymph node spread and distant metastasis make poor prognosis in
      human nasopharyngeal carcinoma (NPC). Therefore, better treatments for NPC are
      needed. This study investigated the anticancer activity of 6-O-angeloylenolin, a
      plant-derived sesquiterpene lactone, on human nasopharyngeal cancer (CNE) cells.
      6-O-Angeloylenolin was found to significantly inhibit the proliferation of CNE
      cells. The rate of inhibition was comparable to that of cisplatin, a well known
      chemotherapeutic agent used to treat NPC. Further mechanistic studies revealed
      that 6-O-angeloylenolin caused cell-cycle arrest in the S and G2/M phases and,
      subsequently, the induction of apoptosis. Rapid repressions of cyclin D1, cyclin
      D3, p27, cdc25c and p-cdc25c (Ser216) were observed after 1-h treatment, followed
      by decreases in the expression of CDK4, cdc2 and p-cdc2 (Tyr15) after 12h. Down
      regulations of p-Rb (Ser780), p21(Waf1/Cip1), cyclin A, and cyclin E were also
      detected as later events. Two early events that marked the occurrence of
      apoptosis were phosphatidylserine exposure and mitochondria membrane potential
      depletion, which occurred after 12h of treatment, while a sub-G1 peak was also
      detected after 36-h treatment. Apoptosis induction was further confirmed by other
      apoptotic features, including nuclear fragmentation, and PARP cleavage. Moreover,
      6-O-angeloylenolin caused the release of cytochrome c and AIF to the cytosol by
      regulating the expression of the Bcl-2 family proteins. However, pretreatment of
      the general caspase inhibitor failed to attenuate the apoptosis induction effect,
      suggesting that apoptosis induction of 6-O-angeloylenolin was independent of
      caspase activation. While 6-O-angeloylenolin also triggered the activation of
      Akt, ERK and JNK, only the JNK inhibitor significantly decreased the extent of
      cell death and apoptosis in CNE cells. Taken together, these results suggest the
      potential applicability of 6-O-angeloylenolin as a candidate for NPC treatment.

PMID- 21192923
TI  - Analytical evaluation of the Tosoh HLC-723 G8 automated HPLC analyzer for
      hemoglobin analysis in beta-thalassemia mode.
AB  - OBJECTIVES: The analytical performances of a new kit conceived for Hb variants
      separation and measurement procedures on an HPLC instrument (Tosoh HLC-723 G8)
      were studied. RESULTS: Between-run and within-run precision tests were
      satisfactory for both HbA2 and HbF measurements. HbA2 and HbF values measured
      using the TOSOH HLC-723 G8 were correlated to those obtained using the Bio-Rad
      Variant II HPLC system (r=0.974 and 0.997 respectively) and to those given by the
      Sebia Capillary's system (r=0.980 and 0.996 respectively). Linearity was observed
      for HbA2 from 2.24% to 6.56% and for HbF from 0.5 to 6%. CONCLUSION: The new
      analyzer Tosoh HLC-723 G8 was found to have a wide analytical range for both HbA2
      and HbF. The G8 Mode beta-thal is suitable for a first-level laboratory screening
      for Hb analysis but also for a second-level test for the characterization of Hb
      variants after a first-line screening.

PMID- 21192924
TI  - Recombinant TFPI-2 enhances macrophage apoptosis through upregulation of
      Fas/FasL.
AB  - Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type serine proteinase
      inhibitor with inhibitory activity toward activated factor XI, plasma kallikrein,
      plasmin, certain matrix metalloproteinases, and the tissue factor-activated
      factor VII complex. In addition, TFPI-2 has other functions such as promoting
      cell migration and inducing apoptosis. In the present study, we investigated if
      TFPI-2 induced apoptosis in cultured U937-derived macrophages and the possible
      signal pathways that involved in the apoptotic process. Apoptotic DNA fragment
      detection and caspase-3,9 activity measurements indicated that rTFPI-2 promoted
      U937-derived macrophage apoptosis. Hoechst 33342 assay and flow cytometry further
      showed that rTFPI-2 induced apoptosis in cultured macrophages in a dose-dependent
      manner. Because death receptors of the TNF family such as Fas are the best
      understood death pathways that recruit Fas-associated death domain (FADD) and
      procaspase-8 to the receptor in macrophages, we investigated the expression of
      Fas and its ligand (FasL) and downstream signal caspase-8 by Western blot
      analysis. The results indicated that the process of apoptosis triggered by rTFPI
      2 was, at least in part, actively conducted by U937-derived macrophages possibly
      through Fas/FasL signal pathway. In brief, rTFPI-2 may have the potential
      usefulness in inducing macrophages apoptosis, which suggest TFPI-2 might have
      antiatherogenic effects.

PMID- 21192925
TI  - Role of the SUMO-interacting motif in HIPK2 targeting to the PML nuclear bodies
      and regulation of p53.
AB  - Homeodomain-interacting protein kinase 2 (HIPK2) is a key regulator of various
      transcription factors including p53 and CtBP in the DNA damage signaling pathway.
      PML-nuclear body (NB) is required for HIPK2-mediated p53 phosphorylation at Ser46
      and induction of apoptosis. Although PML-NB targeting of HIPK2 has been shown,
      much is not clear about the molecular mechanism of HIPK2 recruitment to PML-NBs.
      Here we show that HIPK2 colocalizes specifically with PML-I and PML-IV.
      Mutational analysis showed that HIPK2 recruitment to PML-IV-NBs is mediated by
      the SUMO-interaction motifs (SIMs) of both PML-IV and HIPK2. Wild-type HIPK2
      associated with SUMO-conjugated PML-IV at a higher affinity than with un
      conjugated PML-IV, while the association of a HIPK2 SIM mutant with SUMO-modified
      PML-IV was impaired. In colony formation assays, HIPK2 strongly suppressed cell
      proliferation, but HIPK2 SIM mutants did not. In addition, activation and
      phosphorylation of p53 at the Ser46 residue were impaired by HIPK2 SIM mutants.
      These results suggest that SIM-mediated HIPK2 targeting to PML-NBs is crucial for
      HIPK2-mediated p53 activation and induction of apoptosis.

PMID- 21192927
TI  - Plasticity of urinary bladder reflexes evoked by stimulation of pudendal afferent
      nerves after chronic spinal cord injury in cats.
AB  - Bladder reflexes evoked by stimulation of pudendal afferent nerves (PudA-to
      Bladder reflex) were studied in normal and chronic spinal cord injured (SCI)
      adult cats to examine the reflex plasticity. Physiological activation of pudendal
      afferent nerves by tactile stimulation of the perigenital skin elicits an
      inhibitory PudA-to-Bladder reflex in normal cats, but activates an excitatory
      reflex in chronic SCI cats. However, in both normal and chronic SCI cats
      electrical stimulation applied to the perigenital skin or directly to the
      pudendal nerve induces either inhibitory or excitatory PudA-to-Bladder reflexes
      depending on stimulation frequency. An inhibitory response occurs at 3-10 Hz
      stimulation, but becomes excitatory at 20-30 Hz. The inhibitory reflex activated
      by electrical stimulation significantly (P<0.05) increases the bladder capacity
      to about 180% of control capacity in normal and chronic SCI cats. The excitatory
      reflex significantly (P<0.05) reduces bladder capacity to about 40% of control
      capacity in chronic SCI cats, but does not change bladder capacity in normal
      cats. Electrical stimulation of pudendal afferent nerves during slow bladder
      filling elicits a large amplitude bladder contraction comparable to the
      contraction induced by distension alone. A bladder volume about 60% of bladder
      capacity was required to elicit this excitatory reflex in normal cats; however,
      in chronic SCI cats a volume less than 20% of bladder capacity was sufficient to
      unmask an excitatory response. This study revealed the co-existence of both
      inhibitory and excitatory PudA-to-Bladder reflex pathways in cats before and
      after chronic SCI. However our data combined with published electrophysiological
      data strongly indicates that the spinal circuitry for both the excitatory and
      inhibitory PudA-to-Bladder reflexes undergoes a marked reorganization after SCI.

PMID- 21192926
TI  - Longitudinal behavioral, cross-sectional transcriptional and histopathological
      characterization of a knock-in mouse model of Huntington's disease with 140 CAG
      repeats.
AB  - The discovery of the gene mutation responsible for Huntington's disease (HD),
      huntingtin, in 1993 allowed for a better understanding of the pathology of and
      enabled the development of animal models. HD is caused by the expansion of a
      polyglutamine repeat region in the N-terminal of the huntingtin protein. Here we
      examine the behavioral, transcriptional, histopathological and anatomical
      characteristics of a knock-in HD mouse model with a 140 polyglutamine expansion
      in the huntingtin protein. This CAG 140 model contains a portion of the human
      exon 1 with 140 CAG repeats knocked into the mouse huntingtin gene. We have
      longitudinally examined the rearing behavior, accelerating rotarod, constant
      speed rotarod and gait for age-matched heterozygote, homozygote and non
      transgenic mice and have found a significant difference in the afflicted mice.
      However, while there were significant differences between the non-transgenic and
      the knock-in mice, these behaviors were not progressive. As in HD, we show that
      the CAG 140 mice also have a significant decrease in striatally enriched mRNA
      transcripts. In addition, striatal neuronal intranuclear inclusion density
      increases with age. Lastly these CAG 140 mice show slight cortical thinning
      compared to non-transgenic mice, similarly to the cortical thinning recently
      reported in HD.

PMID- 21192928
TI  - Chronic deprivation of TrkB signaling leads to selective late-onset nigrostriatal
      dopaminergic degeneration.
AB  - The pathological hallmark of Parkinson's disease (PD) is a selective and
      progressive loss of dopaminergic (DA) neurons in the substantia nigra pars
      compacta (SNc). In the vast majority of cases the appearance of PD is sporadic,
      and its etiology remains unknown. Several postmortem studies demonstrate reduced
      levels of brain-derived neurotrophic factor (BDNF) in the SNc of PD patients.
      Application of BDNF promotes the survival of DA neurons in PD animal models. Here
      we show that BDNF signaling via its TrkB receptor tyrosine kinase is important
      for survival of nigrostriatal DA neurons in aging brains. Immunohistochemistry
      revealed that the TrkB receptor was expressed in DA neurons located in the SNc
      and ventral tegmental area (VTA). However, a significant loss of DA neurons
      occurred at 12-24 months of age only in the SNc but not in the VTA of TrkB
      hypomorphic mice in which the TrkB receptor was expressed at a quarter to a third
      of the normal amount. The neuronal loss was accompanied by a decrease in
      dopaminergic axonal terminals in the striatum and by gliosis in both the SNc and
      striatum. Furthermore, nigrostriatal DA neurons in the TrkB mutant mice were
      hypersensitive to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP), a mitochondrial complex I inhibitor that selectively kills DA neurons.
      These results suggest that BDNF-to-TrkB signaling plays an important role in the
      long-term maintenance of the nigrostriatal system and that its deficiency may
      contribute to the progression of PD.

PMID- 21192929
TI  - Modeling of cerebellar hemorrhage.

PMID- 21192930
TI  - Atorvastatin and Abeta(1-40): not as simple as cholesterol reduction in brain and
      relevance to Alzheimer disease.

PMID- 21192931
TI  - Ultra-high resolution crystal structure of a dimeric defensin SPE10.
AB  - Defensins are key players of the innate immune system known to act against
      bacteria, fungi and viruses. Here we report the 0.98-A crystal structure of
      SPE10, a dimeric plant defensin. SPE10 associates as a dimer through a unique
      amino acid triplet involving residues R36-W42-R40. The helix from one subunit
      interacts with arginines R36 and R40 from the other subunit, forming a sheet-like
      dimer with a highly extended molecular surface. A conserved hydrophobic patch on
      the molecular head largely overlaps with the putative receptor-binding site
      previously reported for another defensin. Structural analysis and mutational
      studies indicate that the dimeric association of SPE10 is relevant to its
      function, and that the hydrophobic patch on the molecular head is required for
      its antifungal activity.

PMID- 21192932
TI  - Crystal structures of LacD from Staphylococcus aureus and LacD.1 from
      Streptococcus pyogenes: insights into substrate specificity and virulence gene
      regulation.
AB  - Staphylococcus aureus LacD, a Class I tagatose-1,6-bisphosphate (TBP) aldolase,
      shows broadened substrate specificity by catalyzing the cleavage of 1,6
      bisphosphate derivatives of D-tagatose, D-fructose, D-sorbose, and D-psicose.
      LacD.1 and LacD.2 are two closely-related Class I TBP aldolases in Streptococcus
      pyogenes. Here we have determined the crystal structures of S. aureus LacD and S.
      pyogenes LacD.1. Monomers of both enzymes are folded into a (beta/alpha)(8)
      barrel and two monomers associate tightly to form a dimer in the crystals. The
      structures suggest that the residues E189 and S300 of rabbit muscle Class I
      fructose-1,6-bisphosphate (FBP) aldolase are important for substrate specificity.
      When we mutated the corresponding residues of S. aureus LacD, the mutants (L165E,
      L275S, and L165E/L275S) showed enhanced substrate specificity toward FBP.

PMID- 21192933
TI  - Expression of S100A8/A9 in HaCaT keratinocytes alters the rate of cell
      proliferation and differentiation.
AB  - S100A8/A9 promotes NADPH oxidase in HaCaT keratinocytes and subsequently
      increases NFkappaB activation, which plays important roles in the balance between
      epidermal growth and differentiation. S100A8/A9-positive HaCaT cells present with
      a significantly reduced rate of cell division and greater expression of two
      keratinocyte differentiation markers, involucrin and filaggrin, than control
      cells. S100A8/A9 mutants fail to enhance NFkappaB activation, TNFalpha-induced IL
      8 gene expression and NFkappaB p65 phosphorylation, and S100A8/A9-positive cells
      demonstrate better cell survival in forced suspension culture than mutant cells.
      S100A8/A9 is induced in epithelial cells in response to stress. Therefore,
      S100A8/A9-mediated growth arrest could have implications for tissue remodeling
      and repair.

PMID- 21192934
TI  - Molecular mechanisms of tumor suppression by LKB1.
AB  - The LKB1 tumor suppressor gene is frequently mutated in sporadic lung
      adenocarcinomas and cervical cancers and germline mutations are causative for
      Peutz-Jeghers syndrome characterized by gastrointestinal polyposis. The
      intracellular LKB1 kinase is implicated in regulating polarity, metabolism, cell
      differentiation, and proliferation - all functions potentially contributing to
      tumor suppression. LKB1 acts as an activating kinase of at least 14 kinases
      mediating LKB1 functions in a complex signaling network with partial overlaps.
      Regulation of the LKB1 signaling network is highly context dependent, and
      spatially organized in various cellular compartments. Also the mechanisms by
      which LKB1 activity suppresses tumorigenesis is context dependent, where recent
      observations are providing hints on the molecular mechanisms involved.

PMID- 21192935
TI  - Novel structure of an N-terminal domain that is crucial for the dimeric assembly
      and DNA-binding of an archaeal DNA polymerase D large subunit from Pyrococcus
      horikoshii.
AB  - Archaea-specific D-family DNA polymerase forms a heterotetramer consisting of two
      large polymerase subunits and two small exonuclease subunits. The N-terminal (1
      300) domain structure of the large subunit was determined by X-ray
      crystallography, although ~50 N-terminal residues were disordered. The determined
      structure consists of nine alpha helices and three beta strands. We also
      identified the DNA-binding ability of the domain by SPR measurement. The N
      terminal (1-100) region plays crucial roles in the folding of the large subunit
      dimer by connecting the ~50 N-terminal residues with their own catalytic region
      (792-1163).

PMID- 21192936
TI  - Structural basis for carbon dioxide binding by 2-ketopropyl coenzyme M
      oxidoreductase/carboxylase.
AB  - The structure of 2-ketopropyl coenzyme M oxidoreductase/carboxylase (2-KPCC) has
      been determined in a state in which CO(2) is observed providing insights into the
      mechanism of carboxylation. In the substrate encapsulated state of the enzyme,
      CO(2) is bound at the base of a narrow hydrophobic substrate access channel. The
      base of the channel is demarcated by a transition from a hydrophobic to
      hydrophilic environment where CO(2) is located in position for attack on the
      carbanion of the ketopropyl group of the substrate to ultimately produce
      acetoacetate. This binding mode effectively discriminates against H(2)O and
      prevents protonation of the ketopropyl leaving group.

PMID- 21192937
TI  - Hypoxia-inducible factor independent down-regulation of thioredoxin-interacting
      protein in hypoxia.
AB  - Thioredoxin-Interacting Protein (Txnip) is an important regulator of glucose
      metabolism and functions by inhibiting cellular glucose uptake. The expression of
      the Txnip gene is sensitive to glucose availability and is negatively correlated
      with the glycolytic rate. Here we show that hypoxia induces a rapid decrease in
      Txnip mRNA and protein expression in a Hypoxia-Inducible Factor independent
      manner. Hypoxia caused reduced binding of the glucose responsive MondoA:Mlx
      transcription factor to the carbohydrate response elements (ChoREs) in the Txnip
      promoter. Our data suggest that hypoxia decreases MondoA:Mlx activity by
      increasing glycolytic flux, leading to the depletion of glycolytic intermediates
      which normally activate MondoA:Mlx. Hypoxia dependent Txnip down-regulation may
      be an important compensatory mechanism through which cancer cells adapt their
      metabolism to low oxygen concentrations.

PMID- 21192938
TI  - Use of methylation patterns to determine expansion of stem cell clones in human
      colon tissue.
AB  - BACKGROUND & AIMS: It is a challenge to determine the dynamics of stem cells
      within human epithelial tissues such as colonic crypts. By tracking methylation
      patterns of nonexpressed genes, we have been able to determine how rapidly
      individual stem cells became dominant within a human colonic crypt. We also
      analyzed methylation patterns to study clonal expansion of entire crypts via
      crypt fission. METHODS: Colonic mucosa was obtained from 9 patients who received
      surgery for colorectal cancer. The methylation patterns of Cardiac-specific
      homeobox, Myoblast determination protein 1, and Biglycan were examined within
      clonal cell populations, comprising either part of, or multiple adjacent, normal
      human colonic crypts. Clonality was demonstrated by following cytochrome c
      oxidase-deficient (CCO-) cells that shared an identical somatic point mutation in
      mitochondrial DNA. RESULTS: Methylation pattern diversity among CCO- clones that
      occupied only part of a crypt was proportional to clone size; this allowed us to
      determine rates of clonal expansion. Analysis indicated a slow rate of niche
      succession within the crypt. The 2 arms of bifurcating crypts had distinct
      methylation patterns, indicating that fission can disrupt epigenetic records of
      crypt ancestry. Adjacent clonal CCO- crypts usually had methylation patterns as
      dissimilar to one another as methylation patterns of 2 unrelated crypts.
      Mathematical models indicated that stem cell dynamics and epigenetic drift could
      account for observed dissimilarities in methylation patterns. CONCLUSIONS:
      Methylation patterns can be analyzed to determine the rates of recent clonal
      expansion of stem cells, but determination of clonality over many decades is
      restricted by epigenetic drift. We developed a technique to follow changes in
      intestinal stem cell dynamics in human epithelial tissues that might be used to
      study premalignant disease.

PMID- 21192939
TI  - The contribution of lower vertebrate animal models in human reproduction
      research.
AB  - Many advances have been carried out on the estrogens, GnRH and endocannabinoid
      system that have impact in the reproductive field. Indeed, estrogens, the
      generally accepted female hormones, have performed an unsuspected role in male
      sexual functions thanks to studies on non-mammalian vertebrates. Similarly, these
      animal models have provided important contributions to the identification of
      several GnRH ligand and receptor variants and their possible involvement in
      sexual behavior and gonadal function regulation. Moreover, the use of non
      mammalian animal models has contributed to a better comprehension about the
      endocannabinoid system action in several mammalian reproductive events. We wish
      to highlight here how non-mammalian vertebrate animal model research contributes
      to advancements with implications on human health as well as providing a
      phylogenetic perspective on the evolution of reproductive systems in vertebrates.

PMID- 21192940
TI  - The effects of oral micronized progesterone on smoked cocaine self-administration
      in women.
AB  - There are currently no FDA-approved pharmacotherapies for cocaine abuse.
      Converging preclinical and clinical evidence indicates that progesterone may have
      potential as a treatment for cocaine-abusing women, who represent a growing
      portion of cocaine users. We have previously shown that oral progesterone reduced
      the positive subjective effects of cocaine in female cocaine users during the
      follicular phase of the menstrual cycle, when endogenous progesterone levels were
      low. To extend these findings, the present study assessed the effects of oral
      progesterone (150 mg BID) administered during the follicular phase on smoked
      cocaine self-administration in women relative to the normal follicular and luteal
      phases. Healthy, non-treatment seeking female cocaine smokers (N=10) underwent
      three 4-day inpatient stays, during: 1) a normal follicular phase; 2) a normal
      luteal phase; and 3) a follicular phase when oral progesterone was administered.
      During each stay, participants completed 4 self-administration sessions in which
      they first smoked a "sample" dose of cocaine (0, 12, 25 or 50 mg) and then had 5
      opportunities at 14-minute intervals to self-administer that dose at a cost of $5
      per dose. Expected cocaine dose effects on self-administration, subjective
      effects, and cardiovascular effects were observed. However, there was no effect
      of oral progesterone administration or menstrual cycle phase on cocaine self
      administration. Thus, oral progesterone was not effective in reducing cocaine use
      in women under the current conditions. However, based on previous literature,
      further research assessing the role of oral progesterone for the treatment of
      cocaine dependence in women is warranted.

PMID- 21192941
TI  - Thyrotropin Releasing Hormone (TRH) in goldfish (Carassius auratus): role in the
      regulation of feeding and locomotor behaviors and interactions with the orexin
      system and cocaine- and amphetamine regulated transcript (CART).
AB  - TRH is a peptide produced by the hypothalamus which major function in mammals is
      the regulation of TSH secretion by the pituitary. In fish, TRH does not appear to
      affect TSH secretion, suggesting that it might regulate other functions. In this
      study, we assessed the effects of central (intracerebroventricular, icv)
      injections of TRH on feeding and locomotor behavior in goldfish. TRH at 10 and
      100 ng/g, but not 1 ng/g, significantly increased feeding and locomotor
      behaviors, as indicated by an increase in food intake and in the number of total
      feeding acts as compared to saline-injected fish. In order to assess possible
      interactions between TRH and other appetite regulators, we examined the effects
      of icv injections of TRH on the hypothalamic expression of orexin, orexin
      receptor and CART. The mRNA expression levels of all three peptides were
      significantly increased in fish injected with TRH at 100 ng/g as compared to
      saline-injected fish. Fasting increased TRH, orexin, and orexin receptor
      hypothalamic mRNA levels and decreased CART hypothalamic mRNA levels. Our results
      suggest that TRH is involved in the regulation of feeding/locomotor activity in
      goldfish and that this action is associated with a stimulation of both the orexin
      and CART systems.

PMID- 21192943
TI  - Stability of AtVSP in the insect digestive canal determines its defensive
      capability.
AB  - We have previously demonstrated that Arabidopsis vegetative storage protein
      (AtVSP) is an acid phosphatase that has anti-insect activity in in vitro feeding
      assays [Liu et al., 2005. Plant Physiology 139, 1545-1556]. To investigate the
      functionality of AtVSP in planta as an anti-insect defense protein, we produced
      AtVSP-overexpressing as well as AtVSP-silenced transgenic Arabidopsis lines, and
      evaluated impact on the polyphagous American grasshopper Schistocerca americana.
      Grasshoppers showed no significant difference in weight gain and growth rate when
      feeding on wild type, overexpressing, or silenced lines, respectively. In
      addition, AtVSP protein was undetectable in either the midgut or frass of
      grasshoppers reared on transgenic plants suggesting that AtVSP was unable to
      withstand proteolytic degradation. To determine the stability of the AtVSP
      protein in grasshopper digestive canal, midgut extracts from various nymphal
      stages were incubated with bacterially expressed AtVSP for different periods of
      time. AtVSP was hydrolyzed rapidly by grasshopper midgut extract, in stark
      contrast with its fate when incubated with cowpea bruchid midgut extract.
      Multiple proteases have been detected in the midgut of grasshoppers, which may
      play important roles in determining the insect response to AtVSP. Results
      indicate that stability of an anti-insect protein in insect guts is a crucial
      property integral to the defense protein.

PMID- 21192944
TI  - Proteins within the seminal fluid are crucial to keep sperm viable in the
      honeybee Apis mellifera.
AB  - Seminal fluid is a biochemically complex mixture of glandular secretions that is
      transferred to the females sexual tract as part of the ejaculate. Seminal fluid
      has received increasing scientific interest in the fields of evolutionary and
      reproductive biology, as it seems a major determinant of male
      fertility/infertility and reproductive success. Here we used the honeybee Apis
      mellifera, where seminal fluid can be collected as part of a male's ejaculate,
      and performed a series of experiments to investigate the effects of seminal fluid
      and its components on sperm viability. We show that honeybee seminal fluid is
      highly potent in keeping sperm alive and this positive effect is present over a
      24h time span, comparable to the timing of the sperm storage process in the
      queen. We furthermore show that the presence of proteins within the seminal fluid
      and their structural integrity are crucial for this effect. Finally, we activated
      sperm using fructose and provide evidence that the positive effect of seminal
      fluid proteins on sperm survival cannot be replicated using generic protein
      substitutes. Our data provide experimental insights into the complex molecular
      interplay between sperm and seminal fluid defining male fertility and
      reproductive success.

PMID- 21192942
TI  - A robust, high-throughput assay to determine the phagocytic activity of clinical
      antibody samples.
AB  - Phagocytosis can be induced via the engagement of Fcgamma receptors by antibody
      opsonized material. Furthermore, the efficiency of antibody-induced effector
      functions has been shown to be dramatically modulated by changes in antibody
      glycosylation. Because infection can modulate antibody glycans, which in turn
      modulate antibody functions, assays capable of determining the induction of
      effector functions rather than neutralization or titer provide a valuable
      opportunity to more fully characterize the quality of the adaptive immune
      response. Here we describe a robust and high-throughput flow cytometric assay to
      define the phagocytic activity of antigen-specific antibodies from clinical
      samples. This assay employs a monocytic cell line that expresses numerous Fc
      receptors: including inhibitory and activating, and high and low affinity
      receptors--allowing complex phenotypes to be studied. We demonstrate the
      adaptability of this high-throughput, flow-based assay to measure antigen
      specific antibody-mediated phagocytosis against an array of viruses, including
      influenza, HIV, and dengue. The phagocytosis assay format further allows for
      simultaneous analysis of cytokine release, as well as determination of the role
      of specific Fcgamma-receptor subtypes, making it a highly useful system for
      parsing differences in the ability of clinical and vaccine induced antibody
      samples to recruit this critical effector function.

PMID- 21192945
TI  - Relationships between body weight of overwintering larvae and supercooling
      capacity; diapause intensity and post-diapause reproductive potential in Chilo
      suppressalis Walker.
AB  - The rice stem borer, Chilo suppressalis Walker, overwinters in China as a larva
      in facultative diapause. The instars and body weights of overwintering larvae
      vary widely. In this paper, the relationships between body weight and
      supercooling capacity, diapause intensity and post-diapause reproductive
      potential of overwintering larvae collected in late-stage rice field were
      examined. There was a significant positive correlation between body weight,
      instar, and head capsule width, thus the overwintering larvae were divided into
      five groups based on body weight (I, up to 35.0mg; II, 35.1-57.0mg; III, 57.1
      79.0mg; IV, 79.1-101.0mg; and V, over 101.1mg) for further analysis. The body
      water content of the lighter group (I) was significantly higher than that of the
      heavier groups (IV-V). However, the mean supercooling point decreased with an
      increase of the mean larval body weight in five groups; mean supercooling point
      of group I was significantly lower than that of group V, except in January 2009.
      After transfer of overwintering larvae to 15, 20 and 25 degrees C on different
      dates, smaller individuals pupated slightly faster than larger ones at the same
      temperature, suggesting that diapause was less intense in smaller overwintering
      larvae. On 19 March 2009 there was a strong positive correlation between larval
      body weight and the weight of 3 day-old pupae, and the number of eggs carried by
      2 day-old adult females at 15, 20 and 25 degrees C. The average number of eggs
      carried by 2 day-old adult females differed significantly among different groups.
      The average number of eggs carried by 2 day-old adult females in group V was
      significantly greater than those of other groups, and that of group I was
      significantly lower than those of other groups, suggesting that post-diapause
      reproductive potential was determined, to a certain extent, by body weight of the
      overwintering larvae.

PMID- 21192946
TI  - Full-length sequence, regulation and developmental studies of a second
      vitellogenin gene from the American dog tick, Dermacentor variabilis.
AB  - Vitellogenin (Vg) is the precursor of vitellin (Vn) which is the major yolk
      protein in eggs. In a previous report, we isolated and characterized the first Vg
      message from the American dog tick Dermacentor variabilis. In the current study,
      we describe a second Vg gene from the same tick. The Vg2 cDNA is 5956 nucleotides
      with a 5775 nt open reading frame coding for 1925 amino acids. The conceptual
      amino acid translation contains a 16-residues putative signal peptide, N-terminal
      lipid binding domain and C-terminal von Willebrand factor type D domain present
      in all known Vgs. Moreover, the amino acid sequence shows a typical GLCG domain
      and several RXXR cleavage sites present in most isolated Vgs. Tryptic digest-mass
      fingerprinting of Vg and Vn recognized 11 fragments that exist in the amino acid
      translation of DvVg2 cDNA. Injection of virgin females with 20 hydroxyecdysone
      induced DvVg2 expression, vitellogenesis and oviposition. Using RT-PCR, DvVg2
      expression was detected only in tick females after mating and feeding to
      repletion. Northern blot analysis showed that DvVg2 is expressed in fat body and
      gut cells of vitellogenic females but not in the ovary. DvVg2 expression was not
      detected in adult fed or unfed males. The characteristics that distinguish Vg
      from other similar tick storage proteins like the carrier protein, CP (another
      hemelipoglycoprotein) are discussed.

PMID- 21192947
TI  - Probing membrane protein unfolding with pulse proteolysis.
AB  - Technical challenges have greatly impeded the investigation of membrane protein
      folding and unfolding. To develop a new tool that facilitates the study of
      membrane proteins, we tested pulse proteolysis as a probe for membrane protein
      unfolding. Pulse proteolysis is a method to monitor protein folding and
      unfolding, which exploits the significant difference in proteolytic
      susceptibility between folded and unfolded proteins. This method requires only a
      small amount of protein and, in many cases, may be used with unpurified proteins
      in cell lysates. To evaluate the effectiveness of pulse proteolysis as a probe
      for membrane protein unfolding, we chose Halobacterium halobium bacteriorhodopsin
      (bR) as a model system. The denaturation of bR in SDS has been investigated
      extensively by monitoring the change in the absorbance at 560 nm (A(560)). In
      this work, we demonstrate that denaturation of bR by SDS results in a significant
      increase in its susceptibility to proteolysis by subtilisin. When pulse
      proteolysis was applied to bR incubated in varying concentrations of SDS, the
      remaining intact protein determined by electrophoresis shows a cooperative
      transition. The midpoint of the cooperative transition (C(m)) shows excellent
      agreement with that determined by A(560). The C(m) values determined by pulse
      proteolysis for M56A and Y57A bRs are also consistent with the measurements made
      by A(560). Our results suggest that pulse proteolysis is a quantitative tool to
      probe membrane protein unfolding. Combining pulse proteolysis with Western
      blotting may allow the investigation of membrane protein unfolding in situ
      without overexpression or purification.

PMID- 21192948
TI  - Binding of the inhibitor protein IF(1) to bovine F(1)-ATPase.
AB  - In the structure of bovine F(1)-ATPase inhibited with residues 1-60 of the bovine
      inhibitor protein IF(1), the alpha-helical inhibitor interacts with five of the
      nine subunits of F(1)-ATPase. In order to understand the contributions of
      individual amino acid residues to this complex binding mode, N-terminal deletions
      and point mutations have been introduced, and the binding properties of each
      mutant inhibitor protein have been examined. The N-terminal region of IF(1)
      destabilizes the interaction of the inhibitor with F(1)-ATPase and may assist in
      removing the inhibitor from its binding site when F(1)F(o)-ATPase is making ATP.
      Binding energy is provided by hydrophobic interactions between residues in the
      long alpha-helix of IF(1) and the C-terminal domains of the beta(DP)-subunit and
      beta(TP)-subunit and a salt bridge between residue E30 in the inhibitor and
      residue R408 in the C-terminal domain of the beta(DP)-subunit. Several conserved
      charged amino acids in the long alpha-helix of IF(1) are also required for
      establishing inhibitory activity, but in the final inhibited state, they are not
      in contact with F(1)-ATPase and occupy aqueous cavities in F(1)-ATPase. They
      probably participate in the pathway from the initial interaction of the inhibitor
      and the enzyme to the final inhibited complex observed in the structure, in which
      two molecules of ATP are hydrolysed and the rotor of the enzyme turns through two
      120 degrees  steps. These findings contribute to the fundamental understanding of
      how the inhibitor functions and to the design of new inhibitors for the
      systematic analysis of the catalytic cycle of the enzyme.

PMID- 21192949
TI  - Antagonistic control of microbial pathogens under iron limitations by siderophore
      producing bacteria in a chemostat setup.
AB  - Certain bacteria develop iron chelation mechanisms that allow them to scavenge
      dissolved iron from the environment and to make it unavailable to competitors.
      This is achieved by producing siderophores that bind the iron which is later
      liberated internally in the cell. Under conditions of iron limitation,
      siderophore producing bacteria have therefore an antagonistic growth advantage
      over other species. This has been observed in particular in agricultural and
      aquacultural systems, as well as in food microbiology. We investigate here the
      possibility of a probiotic biocontrol strategy to eradicate a well established,
      often pathogenic, non-chelating population by supplementing the system with
      generally regarded as safe siderophore producing bacteria. Set in a chemostat
      setup, our modeling and simulation studies suggest that this is indeed possible
      in a finite time treatment.

PMID- 21192950
TI  - Optimal choice of species and size class for transplanting coral community.
AB  - Transplantation of sessile organisms living in a planned destruction site to a
      safe site is an important means of restoration to mitigate biodiversity loss
      following anthropogenic developments. In particular, corals, which play
      fundamental roles in the coral reef ecosystem and contribute to biodiversity, are
      good candidates for transplantation. In this study, we investigate the optimal
      choice of species and size class to be used for coral transplantation. We first
      studied a case in which the objective function to evaluate the success of
      transplantation is the maximum total coverage. The optimal strategy is to choose
      the species and size class with higher net coverage gain per unit handling
      effort. It is often recommended to transplant only one or a few species and
      neglect others, even if the original community consists of many species. This may
      achieve high coverage in the restored coral community but cause loss of species
      diversity. To overcome this problem, we next study a case in which the objective
      of the transplantation operation is to maximize the "prosperity index", defined
      as the product of total coverage and species diversity. In this case, the optimal
      strategy depends on the species property, population size, and the limitation of
      total cost allowed for transplantation, but it tends to recommend more species to
      be transplanted than what is recommended by the coverage maximization criterion.
      We conclude that maximization of the prosperity index is a better criterion for
      transplantation than simple coverage maximization.

PMID- 21192951
TI  - Non-linear models based on simple topological indices to identify RNase III
      protein members.
AB  - Alignment-free classifiers are especially useful in the functional classification
      of protein classes with variable homology and different domain structures. Thus,
      the Topological Indices to BioPolymers (TI2BioP) methodology (Aguero-Chapin et
      al., 2010) inspired in both the TOPS-MODE and the MARCH-INSIDE methodologies
      allows the calculation of simple topological indices (TIs) as alignment-free
      classifiers. These indices were derived from the clustering of the amino acids
      into four classes of hydrophobicity and polarity revealing higher sequence-order
      information beyond the amino acid composition level. The predictability power of
      such TIs was evaluated for the first time on the RNase III family, due to the
      high diversity of its members (primary sequence and domain organization). Three
      non-linear models were developed for RNase III class prediction: Decision Tree
      Model (DTM), Artificial Neural Networks (ANN)-model and Hidden Markov Model
      (HMM). The first two are alignment-free approaches, using TIs as input
      predictors. Their performances were compared with a non-classical HMM, modified
      according to our amino acid clustering strategy. The alignment-free models showed
      similar performances on the training and the test sets reaching values above 90%
      in the overall classification. The non-classical HMM showed the highest rate in
      the classification with values above 95% in training and 100% in test. Although
      the higher accuracy of the HMM, the DTM showed simplicity for the RNase III
      classification with low computational cost. Such simplicity was evaluated in
      respect to HMM and ANN models for the functional annotation of a new bacterial
      RNase III class member, isolated and annotated by our group.

PMID- 21192953
TI  - Parameter identification in epidemic models.
AB  - Starting from a recent paper of Pollicott, Wang and Weiss we try to obtain
      improved representation formulas for the estimation of the time-dependent
      transmission rate of an epidemic in terms of either incidence or prevalence data.
      Although the formulas are (trivially) mathematically equivalent to previous
      formulas, the new representations need no additional estimates and they should be
      more stable numerically. We review the discrete time and the stochastic
      continuous time approach. We replace the assumption that recovery follows an
      exponential distribution and get estimates for the transmission rate for constant
      duration of the infectious phase.

PMID- 21192952
TI  - Inhibitory effects of the HDAC inhibitor valproic acid on prostate cancer growth
      are enhanced by simultaneous application of the mTOR inhibitor RAD001.
AB  - AIMS: To analyze the combined impact of the histone deacetylase (HDAC) inhibitor
      valproic acid (VPA) and the mammalian target of rapamycin (mTOR) inhibitor RAD001
      on prostate cancer cell growth. MAIN METHODS: PC-3, DU-145 and LNCaP cells were
      treated with RAD001, VPA or with an RAD001-VPA combination for 3 or 5 days. Tumor
      cell growth, cell cycle progression and cell cycle regulating proteins were then
      investigated by MTT assay, flow cytometry and Western blotting, respectively.
      Effects of drug treatment on cell signaling pathways were determined. KEY
      FINDINGS: Separate application of RAD001 or VPA distinctly reduced tumor cell
      growth and impaired cell cycle progression. Significant additive effects were
      evoked when both drugs were used in concert. Particularly, the cell cycle
      regulating proteins cdk1, cdk2, cdk4 and cyclin B were reduced, whereas p21 and
      p27 were enhanced by the RAD001-VPA combination. Signaling analysis revealed
      deactivation of EGFr, ERK1/2 and p70S6k. Phosphorylation of Akt was diminished in
      DU-145 but elevated in PC-3 and LNCaP cells. SIGNIFICANCE: The RAD001-VPA
      combination exerted profound antitumor properties on a panel of prostate cancer
      cell lines. Therefore, simultaneous blockage of HDAC and mTOR related pathways
      should be considered when designing novel therapeutic strategies for treating
      prostate carcinoma.

PMID- 21192954
TI  - Dynamics of dystroglycan complex proteins and laminin changes due to angiogenesis
      in rat cerebral hypoperfusion.
AB  - Permanent bilateral carotid occlusion is a well known cerebral hypoperfusion
      model in rats. The aim of our study was to investigate the different stages of
      vascular reaction by detecting changes in the extracellular martix proteins and
      to examine their relationship to angiogenesis after occlusion. Experiments were
      performed on adult male rats. Brain samples were investigated from day 1 to day
      30 post-surgery. Immunohistochemical analysis was performed on the whole
      hippocampus and on the adjacent cortex in order to investigate extracellular
      martix proteins, such as the markers of dystroglycan complex (beta-dystroglycan,
      alpha-dystrobrevin and utrophin) and a marker of basal lamina (laminin). The
      levels of the proteins were estimated by western blot analysis. Vascular density
      as well as blood-brain barrier permeability were studied on brain slices from the
      same regions. Our results showed altered laminin and beta-dystroglycan
      immunoreactivity beginning 2 days after the onset of occlusion followed by an
      increased utrophin immunoreactivity without blood-brain barrier disruption 5 days
      later. By day 30 of hypoperfusion, when increased vascular density was detected,
      all changes returned to baseline levels. Western blot analysis showed significant
      differences in beta-dystroglycan and utrophin expression. Our results indicate
      that the different stages of neovascularisation resulting from cerebral
      hypoperfusion can be well defined by the markers laminin, beta-dystroglycan, and
      utrophin and that these markers are more likely to correlate with glio-vascular
      decoupling than does altered blood-brain barrier function.

PMID- 21192955
TI  - Angioarchitectural heterogeneity in human glioblastoma multiforme: a fractal
      based histopathological assessment.
AB  - There is currently no standard technique to objectively quantify the
      microvascularization of brain tumors. Fractal analysis has been proposed as a
      useful descriptor of tumor microvascularity. Standardization of the fractal
      analysis methodology could offer a new tool for this type of characterization. In
      this study, we applied fractal analysis to the characterization of the different
      angioarchitectures found in specimens of glioblastoma multiforme (GBM), the most
      common and most malignant type of human brain tumor. A retrospective series of
      114 primary GBM specimens was carried out. To quantify neoplastic
      microvascularity, the level of two-dimensional geometrical complexity of the
      microvascular patterns was assessed using the box-counting algorithm, which
      estimates the microvascular fractal dimension (mvFD). mvFD makes information on
      the non-Euclidean space filled by vessels embedded in the tumor microenvironment
      available because it depends on vessel number, shape, magnitude and distribution
      pattern. A mean mvFD value of 1.44 +/- 0.17 (range: 1.06-1.87) was found. The
      coefficient of variation was 44%. The high geometric variability, found
      objectively, in these samples reflects the angioarchitectural heterogeneity
      underlying GBM. The present study shows that angioarchitectural subtypes can be
      identified by mvFD, making this parameter a potential tool for quantifying
      different neoplastic microvascular patterns.

PMID- 21192956
TI  - Age and 17beta-estradiol effects on blood-brain barrier tight junction and
      estrogen receptor proteins in ovariectomized rats.
AB  - Age and estrogen levels alter blood-brain barrier (BBB) tight junction (TJ)
      regulation, impacting brain homeostasis and pathological outcomes. This
      examination evaluated BBB TJ and estrogen receptor (ER) protein expression
      changes in young (8-10 week) and middle-aged (10-12 month) ovariectomized female
      Fisher-344 rats with chronic 17beta-estradiol or placebo treatment. Middle-aged
      rats showed decreased protein expression of occludin with 17beta-estradiol (55
      kDa band) or placebo (45, 55, 60 kDa bands) treatment compared to respective
      young. In young animals, 17beta-estradiol treatment increased expression of the
      occludin 55 kDa band over placebo; however, this effect was lost in the middle
      aged animals. In both young and middle-aged animals, expression of claudin-5 (23,
      32 kDa bands) and ERalpha (66 kDa) increased with 17beta-estradiol treatment,
      while junctional adhesion molecule-A showed no change across all groups. However,
      ERalpha expression (66 kDa) was significantly reduced in the middle-aged animals
      compared to young placebo treated animals. Measurement of BBB TJ permeability via
      in situ perfusion of (14)C-sucrose showed no change with age or treatment. Our
      results show that increasing age and 17beta-estradiol treatment alters the
      expression of ERalpha and distinct BBB TJ protein isoforms without altering
      functional paracellular permeability.

PMID- 21192957
TI  - The neuropsychology of prospective memory in normal aging: a componential
      approach.
AB  - To guide understanding of the neuropsychology of prospective memory and aging, we
      highlight several components of prospective memory, including planning an
      intended action, retrieving the action at the appropriate moment, and executing
      the action. We posit that frontal systems are particularly important for
      prospective memory tasks that require planning, that require strategic monitoring
      to detect the appropriate moment for executing the prospective memory intention,
      or for which execution of the retrieved intention must be delayed briefly.
      Drawing from a variety of approaches, including neuroimaging (with young adults)
      and studies examining individual differences relating to frontal functioning, we
      assemble preliminary evidence that supports this hypothesis. Further, because
      aging especially disrupts frontal functioning, the above noted prospective memory
      tasks would thus be expected to display the greatest age-related decline. The
      available literature confirms this expectation. A second key hypothesis is that
      some prospective memory tasks--those requiring minimal planning and supporting
      spontaneous retrieval--do not rely extensively on frontal processes but instead
      rely on medial-temporal structures for reflexive retrieval. These prospective
      memory tasks tend to show minimal or no age-related decline. The literature,
      though sparse with regard to the neuropsychological underpinnings of this kind of
      prospective memory task, is consistent with the present hypothesis.

PMID- 21192958
TI  - Atypical processing of auditory temporal complexity in autistics.
AB  - Autistics exhibit a contrasting combination of auditory behavior, with enhanced
      pitch processing abilities often coexisting with reduced orienting towards
      complex speech sounds. Based on an analogous dissociation observed in vision, we
      expected that autistics' auditory behavior with respect to complex sound
      processing may result from atypical activity in non-primary auditory cortex. We
      employed fMRI to explore the neural basis of complex non-social sound processing
      in 15 autistic and 13 non-autistics, using a factorial design in which auditory
      stimuli varied in spectral and temporal complexity. Spectral complexity was
      modulated by varying the harmonic content, whereas temporal complexity was
      modulated by varying frequency modulation depth. The detection task was performed
      similarly by autistics and non-autistics. In both groups, increasing spectral or
      temporal complexity was associated with activity increases in primary (Heschl's
      gyrus) and non-primary (anterolateral and posterior superior temporal gyrus)
      auditory cortex Activity was right-lateralized for spectral and left-lateralized
      for temporal complexity. Increasing temporal complexity was associated with
      greater activity in anterolateral superior temporal gyrus in non-autistics and
      greater effects in Heschl's gyrus in autistics. While we observed similar
      hierarchical functional organization for auditory processing in both groups,
      autistics exhibited diminished activity in non-primary auditory cortex and
      increased activity in primary auditory cortex in response to the presentation of
      temporally, but not of spectrally complex sounds. Greater temporal complexity
      effects in regions sensitive to acoustic features and reduced temporal complexity
      effects in regions sensitive to more abstract sound features could represent a
      greater focus towards perceptual aspects of speech sounds in autism.

PMID- 21192960
TI  - Noise exposure during early development influences the acoustic startle reflex in
      adult rats.
AB  - Noise exposure during the critical period of postnatal development in rats
      results in anomalous processing of acoustic stimuli in the adult auditory system.
      In the present study, the behavioral consequences of an acute acoustic trauma in
      the critical period are assessed in adult rats using the acoustic startle reflex
      (ASR) and prepulse inhibition (PPI) of ASR. Rat pups (strain Long-Evans) were
      exposed to broad-band noise of 125 dB SPL for 8 min on postnatal day 14; at the
      age of 3-5 months, ASR and PPI of ASR were examined and compared with those
      obtained in age-matched controls. In addition, hearing thresholds were measured
      in all animals by means of auditory brainstem responses. The results show that
      although the hearing thresholds in both groups of animals were not different, a
      reduced strength of the startle reflex was observed in exposed rats compared with
      controls. The efficacy of PPI in exposed and control rats was also markedly
      different. In contrast to control rats, in which an increase in prepulse
      intensity was accompanied by a consistent increase in the efficacy of PPI, the
      PPI function in the exposed animals was characterized by a steep increase in
      inhibitory efficacy at low prepulse intensities of 20-30 dB SPL. A further
      increase of prepulse intensity up to 60-70 dB SPL caused only a small and
      insignificant change of PPI. Our findings demonstrate that brief noise exposure
      in rat pups results in altered behavioral responses to sounds in adulthood,
      indicating anomalies in intensity coding and loudness perception.

PMID- 21192959
TI  - Grounding emotion in situated conceptualization.
AB  - According to the Conceptual Act Theory of Emotion, the situated conceptualization
      used to construe a situation determines the emotion experienced. A neuroimaging
      experiment tested two core hypotheses of this theory: (1) different situated
      conceptualizations produce different forms of the same emotion in different
      situations, (2) the composition of a situated conceptualization emerges from
      shared multimodal circuitry distributed across the brain that produces emotional
      states generally. To test these hypotheses, the situation in which participants
      experienced an emotion was manipulated. On each trial, participants immersed
      themselves in a physical danger or social evaluation situation and then
      experienced fear or anger. According to Hypothesis 1, the brain activations for
      the same emotion should differ as a function of the preceding situation (after
      removing activations that arose while constructing the situation). According to
      Hypothesis 2, the critical activations should reflect conceptual processing
      relevant to the emotion in the current situation, drawn from shared multimodal
      circuitry underlying emotion. The results supported these predictions and
      demonstrated the compositional process that produces situated conceptualizations
      dynamically.

PMID- 21192961
TI  - Pharmacological evidence that Ca2+ channels and, to a lesser extent, K+ channels
      mediate the relaxation of testosterone in the canine basilar artery.
AB  - Testosterone induces vasorelaxation through non-genomic mechanisms in several
      isolated blood vessels, but no study has reported its effects on the canine
      basilar artery, an important artery implicated in cerebral vasospasm. Hence, this
      study has investigated the mechanisms involved in testosterone-induced relaxation
      of the canine basilar artery. For this purpose, the vasorelaxant effects of
      testosterone were evaluated in KCl- and/or PGF(2alpha)-precontracted arterial
      rings in vitro in the absence or presence of several
      antagonists/inhibitors/blockers; the effect of testosterone on the contractile
      responses to CaCl2 was also determined. Testosterone (10-180 MUM) produced
      concentration-dependent relaxations of KCl- or PGF(2alpha)-precontracted arterial
      rings which were: (i) unaffected by flutamide (10 MUM), DL-aminoglutethimide (10
      MUM), actinomycin D (10 MUM), cycloheximide (10 MUM), SQ 22,536 (100 MUM) or ODQ
      (30 MUM); and (ii) significantly attenuated by the blockers 4-aminopyridine
      (K(V); 1 mM), BaCl2 (K(IR); 30 MUM), iberiotoxin (BK(Ca2+); 20 nM), but not by
      glybenclamide (K(ATP); 10 MUM). In addition, testosterone (31, 56 and 180 MUM)
      and nifedipine (0.01-1 MUM) produced a concentration-dependent blockade of the
      contraction to CaCl2 (10 MUM to 10 mM) in arterial rings depolarized by 60mM KCl.
      These results, taken together, show that testosterone relaxes the canine basilar
      artery mainly by blockade of voltage-dependent Ca2+ channels and, to a lesser
      extent, by activation of K+ channels (K(IR), K(V) and BK(Ca2+)). This effect does
      not involve genomic mechanisms, production of cAMP/cGMP or the conversion of
      testosterone to 17beta-estradiol.

PMID- 21192962
TI  - Effects of genetic architecture on the evolution of assortative mating under
      frequency-dependent disruptive selection.
AB  - We consider a model of sympatric speciation due to frequency-dependent
      competition, in which it was previously assumed that the evolving traits have a
      very simple genetic architecture. In the present study, we numerically analyze
      the consequences of relaxing this assumption. First, previous models assumed that
      assortative mating evolves in infinitesimal steps. Here, we show that the range
      of parameters for which speciation is possible increases when mutational steps
      are large. Second, it was assumed that the trait under frequency-dependent
      selection is determined by a single locus with two alleles and additive effects.
      As a consequence, the resultant intermediate phenotype is always heterozygous and
      can never breed true. To relax this assumption, here we add a second locus
      influencing the trait. We find three new possible evolutionary outcomes:
      evolution of three reproductively isolated species, a monomorphic equilibrium
      with only the intermediate phenotype, and a randomly mating population with a
      steep unimodal distribution of phenotypes. Both extensions of the original model
      thus increase the likelihood of competitive speciation.

PMID- 21192963
TI  - Concentration-dependent gene expression responses to flusilazole in embryonic
      stem cell differentiation cultures.
AB  - The murine embryonic stem cell test (EST) is designed to evaluate developmental
      toxicity based on compound-induced inhibition of embryonic stem cell (ESC)
      differentiation into cardiomyocytes. The addition of transcriptomic evaluation
      within the EST may result in enhanced predictability and improved
      characterization of the applicability domain, therefore improving usage of the
      EST for regulatory testing strategies. Transcriptomic analyses assessing factors
      critical for risk assessment (i.e. dose) are needed to determine the value of
      transcriptomic evaluation in the EST. Here, using the developmentally toxic
      compound, flusilazole, we investigated the effect of compound concentration on
      gene expression regulation and toxicity prediction in ESC differentiation
      cultures. Cultures were exposed for 24 h to multiple concentrations of
      flusilazole (0.54-54 MUM) and RNA was isolated. In addition, we sampled control
      cultures 0, 24, and 48 h to evaluate the transcriptomic status of the cultures
      across differentiation. Transcriptomic profiling identified a higher sensitivity
      of development-related processes as compared to cell division-related processes
      in flusilazole-exposed differentiation cultures. Furthermore, the sterol
      synthesis-related mode of action of flusilazole toxicity was detected. Principal
      component analysis using gene sets related to normal ESC differentiation was used
      to describe the dynamics of ESC differentiation, defined as the 'differentiation
      track'. The concentration-dependent effects on development were reflected in the
      significance of deviation of flusilazole-exposed cultures from this
      transcriptomic-based differentiation track. Thus, the detection of developmental
      toxicity in EST using transcriptomics was shown to be compound concentration
      dependent. This study provides further insight into the possible application of
      transcriptomics in the EST as an improved alternative model system for
      developmental toxicity testing.

PMID- 21192964
TI  - XPC is essential for nucleotide excision repair of zidovudine-induced DNA damage
      in human hepatoma cells.
AB  - Zidovudine (3'-azido-3'-dexoythymidine, AZT), a nucleoside reverse transcriptase
      inhibitor, can be incorporated into DNA and cause DNA damage. The mechanisms
      underlying the repair of AZT-induced DNA damage are unknown. To investigate the
      pathways involved in the recognition and repair of AZT-induced DNA damage, human
      hepatoma HepG2 cells were incubated with AZT for 2 weeks and the expression of
      DNA damage signaling pathways was determined using a pathway-based real-time PCR
      array. Compared to control cultures, damaged DNA binding and nucleotide excision
      repair (NER) pathways showed significantly increased gene expression. Further
      analysis indicated that AZT treatment increased the expression of genes
      associated with NER, including XPC, XPA, RPA1, GTF2H1, and ERCC1. Western blot
      analysis demonstrated that the protein levels of XPC and GTF2H1 were also
      significantly up-regulated. To explore further the function of XPC in the repair
      of AZT-induced DNA damage, XPC expression was stably knocked down by 71% using
      short hairpin RNA interference. In the XPC knocked-down cells, 100 MUM AZT
      treatment significantly increased [3H]AZT incorporation into DNA, decreased the
      total number of viable cells, increased the release of lactate dehydrogenase,
      induced apoptosis, and caused a more extensive G2/M cell cycle arrest when
      compared to non-transfected HepG2 cells or HepG2 cells transfected with a
      scrambled short hairpin RNA sequence. Overall, these data indicate that XPC plays
      an essential role in the NER repair of AZT-induced DNA damage.

PMID- 21192965
TI  - An explanation of perisaccadic compression of visual space.
AB  - A large number of experiments show that perisaccadic flash mislocalization can
      vary according to the spatial location of the flash relative to the saccade,
      especially in the presence of background stimuli. The temporal attributes of this
      mislocalization suggest that, around the time of a saccade, a transient
      compression of visual space occurs. The present study offers a model to account
      for such compression. A basic aspect of the model is that the mislocalization is
      a consequence of flash retinal signal persistence interacting with an
      extraretinal signal. Of central importance, however, the model suggests that the
      extraretinal signal is different when a saccade occurs in the dark from when a
      saccade occurs with background stimuli. In the dark, the extraretinal signal
      begins to change with little or no time difference from one retinal locus to
      another, resulting in little or no compression. However, in the presence of
      background stimuli, the extraretinal signal begins at considerably different
      times across the retina, giving rise to a large amount of compression.

PMID- 21192967
TI  - D-cycloserine selectively decreases nicotine self-administration in rats with low
      baseline levels of response.
AB  - Expanding the variety of treatments available to aid smoking cessation will allow
      the treatments to be customized to particular types of smokers. The key is to
      understand which subpopulations of smokers respond best to which treatment. This
      study used adult female Sprague-Dawley rats to evaluate the efficacy of D
      cycloserine, a partial NMDA glutamate receptor agonist, in reducing nicotine self
      administration. Rats were trained to self-administer nicotine (0.03
      mg/kg/infusion, i.v.) via operant lever response (FR1) with a secondary visual
      reinforcer. Two studies of D-cycloserine effects on nicotine self-administration
      were conducted: an acute dose-effect study (0, 10, 20 and 40 mg/kg, s.c.) and a
      chronic study with 40 mg/kg given before each test session for two weeks. Effects
      on rats with low or high pretreatment baseline levels of nicotine self
      administration were assessed. In the acute study there was a significant
      interaction of D-cycloserine*baseline level of nicotine self-administration. In
      the low baseline group, 10 mg/kg D-cycloserine significantly decreased nicotine
      self-administration. In the high baseline group, 40 mg/kg significantly increased
      nicotine self-administration. In the repeated injection study, there was also a
      significant interaction of d-cycloserine*baseline level of nicotine self
      administration. Chronic D-cycloserine significantly reduced nicotine self
      administration selectively in rats with low baseline nicotine use, but was
      ineffective with the rats with higher levels of baseline nicotine self
      administration. NMDA glutamate treatments may be particularly useful in helping
      lighter smokers successfully quit smoking, highlighting the need for diverse
      treatments for different types of smokers.

PMID- 21192968
TI  - Sustained antagonism of acute ethanol-induced ataxia following microinfusion of
      cyclic AMP and cpt-cAMP in the mouse cerebellum.
AB  - Ataxia is a conspicuous physical manifestation of alcohol consumption in humans
      and laboratory animals. Previously we reported possible involvement of cAMP in
      ethanol-induced ataxia. We now report a sustained antagonism of ataxia due to
      multiple ethanol injections following intracerebellar (ICB) cAMP or cpt-cAMP
      microinfusion. Adenylyl cyclase drugs cAMP, cpt-cAMP, Sp-cAMP, Rp-cAMP, adenosine
      A1 agonist, N6-cyclohexyladenosine (CHA) and GABA(A) agonist muscimol were
      directly microinfused into the cerebellum of CD-1 male mice to evaluate their
      effect on ethanol (2 g/kg; i.p.) ataxia. Drug microinfusions were made via
      stereotaxically implanted stainless steel guide cannulas. Rotorod was used to
      evaluate the ethanol's ataxic response. Intracerebellar cAMP (0.1, 1, 10 fmol) or
      cpt-cAMP (0.5, 1, 2 fmol) 60 min before ethanol treatment, dose-dependently
      attenuated ethanol-induced ataxia in general agreement with previous
      observations. Intracerebellar microinfusion of cAMP (100 fmol) or cpt-cAMP (2
      fmol) produced a sustained attenuation of ataxia following ethanol administration
      at 1, 4, 7 and 25 h or 31 h post-cAMP/cpt-cAMP microinfusion. At 31 h post-cAMP,
      the ataxic response of ethanol reappeared. Additionally, marked antagonism to the
      accentuation of ethanol-induced ataxia by adenosine A1 and GABA(A) agonists, CHA
      (34 pmol) and muscimol (88 pmol), respectively, was noted 24h after cAMP and cpt
      cAMP treatment. This indicated possible participation of AC/cAMP/PKA signaling in
      the co-modulation of ethanol-induced ataxia by A1 adenosinergic and GABAergic
      systems. No change in normal motor coordination was noted when cAMP or cpt-cAMP
      microinfusion was followed by saline. Finally, Rp-cAMP (PKA inhibitor, 22 pmol)
      accentuated ethanol-induced ataxia and antagonized its attenuation by cAMP
      whereas Sp-cAMP (PKA activator, 22 pmol) produced just the opposite effects,
      further indicating participation of cAMP-dependent PKA downstream. Overall, the
      results support a role of AC/cAMP/PKA signaling in the expression of ethanol
      induced ataxia and its co-modulation by adenosine A1 and GABA(A) receptors.

PMID- 21192966
TI  - A neuroendocrine basis for the hierarchical control of frog courtship
      vocalizations.
AB  - Seasonal courtship signals, such as mating calls, are orchestrated by steroid
      hormones. Sex differences are also sculpted by hormones, typically during brief
      sensitive periods. The influential organizational-activational hypothesis [50]
      established the notion of a strong distinction between long-lasting
      (developmental) and cyclical (adult) effects. While the dichotomy is not always
      strict [1], experimental paradigms based on this hypothesis have indeed revealed
      long-lasting hormone actions during development and more transient anatomical,
      physiological and behavioral effects of hormonal variation in adulthood. Sites of
      action during both time periods include forebrain and midbrain sensorimotor
      integration centers, hindbrain and spinal cord motor centers, and muscles.
      African clawed frog (Xenopus laevis) courtship vocalizations follow the basic
      organization-activation pattern of hormone-dependence with some exceptions,
      including expanded steroid-sensitive periods. Two highly-tractable preparations
      the isolated larynx and the fictively calling brain-make this model system
      powerful for dissecting the hierarchical action of hormones. We discuss steroid
      effects from larynx to forebrain, and introduce new directions of inquiry for
      which Xenopus vocalizations are especially well-suited.

PMID- 21192969
TI  - 5-HT6 pharmacology inconsistencies.
AB  - 5-HT(6) receptors are relatively recently-discovered receptors. After an
      uncertain beginning, where results were ambiguous, findings are now apparently
      more congruent. Nevertheless, discrepancies still exist. The aim of the present
      manuscript is to point out some of these discrepancies, in order to reflect on
      the current status of the field of the 5-HT(6) receptor neuropharmacology, and
      where the field should move next. Examples of 5-HT(6) receptor ligand-induced
      changes in behavior, neurochemistry and binding highlight areas where
      discrepancies remain and further experimental attention is needed. Possible
      methodological as well as conceptual issues underlying the inconsistencies are
      considered in an effort to increase awareness of the need for more thorough
      consideration of these aspects in future research.

PMID- 21192970
TI  - A type Ib plasmid segregation machinery of the Advenella kashmirensis plasmid
      pBTK445.
AB  - pBTK445 is a newly described large (~60Kb), low-copy number, conjugative plasmid
      indigenous to the sulfur-chemolithoautotroph Advenella kashmirensis. Based on its
      minimal replication region, a shuttle vector, pBTKS was constructed which can be
      used for diverse Alcaligenaceae members. The construct was found to be stably
      maintained both in the native host as well as in Escherichia coli in the absence
      of selective pressure which indicated that pBTKS harbors the stabilizing system
      of pBTK445, that are commonly coded by low-copy-number plasmids. Deletion
      analyzes of pBTKS confirmed the essentiality of parA (encoding a Walker-type
      ATPase of 214 amino acids) and the downstream located small parB (encoding an 85
      amino acid protein having no sequence homolog in the database) in the faithful
      partitioning of pBTK445. A 1075bp PCR product, containing parA, parB and an
      upstream sequence having nine 11bp direct repeats (parS site) was found to
      comprise the partition functions of pBTK445, stabilizing both low-copy or high
      copy number homologous and heterologous replicons in diverse hosts. The
      incompatibility determinant and the par promoter, P(par) were both found to be
      present within a 191bp iterated sequence present upstream of parA. ParB was found
      to regulate the expression of the Par proteins from P(par). The presence of a
      typical Walker-type ATPase motif in ParA, a short phylogenetically unrelated
      ParB, that acts as a repressor of P(par), and location of the iterated parS site
      upstream of parA, confirm that the active partition system of pBTK445 belongs to
      the type Ib.

PMID- 21192971
TI  - The 'resting-state hypothesis' of major depressive disorder-a translational
      subcortical-cortical framework for a system disorder.
AB  - Major depressive disorder (MDD) has traditionally been characterized by various
      psychological symptoms, involvement of diverse functional systems (e.g., somatic,
      affect, cognition, reward, etc.), and with progress in neuroscience, an
      increasing number of brain regions. This has led to the general assumption that
      MDD is a stress-responsive brain 'system disorder' where either one or several
      alterations infiltrate a large number of functional systems in the brain that
      control the organism's somatic, affective, and cognitive life. However, while the
      effects or consequences of the abnormal changes in the functional systems of, for
      instance affect, cognition or reward have been investigated extensively, the
      underlying core mechanism(s) underlying MDD remain unknown. Hypotheses are
      proliferating rapidly, though. Based on recent findings, we will entertain an
      abnormality in the resting-state activity in MDD to be a core feature. Based on
      both animal and human data, we hypothesize that abnormal resting-state activity
      levels may impact stimulus-induced neural activity in medially situated core
      systems for self-representation as well as external stimulus (especially stress,
      specifically separation distress) interactions. Moreover, due to nested hierarchy
      between subcortical and cortical regions, we assume 'highjacking' of higher
      cortical affective and cognitive functions by lower subcortical primary-process
      emotional systems. This may account for the predominance of negative affect in
      somatic and cognitive functional system operations with the consecutive
      generation of the diverse symptoms in MDD. We will here focus on the
      neuroanatomical and biochemical basis of resting-state abnormalities in MDD
      including their linkage to the diverse psychopathological symptoms in depression.
      However, our 'resting-state hypothesis' may go well beyond that by being
      sufficiently precise to be linked to genetic, social, immunological, and
      endocrine dimensions and hypotheses as well as to clinical dimensions like
      endophenotypes and various diagnostic-prognostic biomarkers. Taken together, our
      'resting-state hypothesis' may be considered a first tentative framework for MDD
      that integrates translational data, the various dimensions, and subcortical
      cortical systems while at the same time providing the link to the clinical level
      of symptoms, endophenotypes and biomarkers.

PMID- 21192972
TI  - Lead exposure during synaptogenesis alters NMDA receptor targeting via NMDA
      receptor inhibition.
AB  - N-methyl-D-aspartate receptor (NMDAR) ontogeny and subunit expression are altered
      during developmental lead (Pb2+) exposure. However, it is unknown whether these
      changes occur at the synaptic or cellular level. Synaptic and extra-synaptic
      NMDARs have distinct cellular roles, thus, the effects of Pb2+ on NMDAR synaptic
      targeting may affect neuronal function. In this communication, we show that Pb2+
      exposure during synaptogenesis in hippocampal neurons altered synaptic NMDAR
      composition, resulting in a decrease in NR2A-containing NMDARs at established
      synapses. Conversely, we observed increased targeting of the obligatory NR1
      subunit of the NMDAR to the postsynaptic density (PSD) based on the increased
      colocalization with the postsynaptic protein PSD-95. This finding together with
      increased binding of the NR2B-subunit specific ligand [3H]-ifenprodil, suggests
      increased targeting of NR2B-NMDARs to dendritic spines as a result of Pb2+
      exposure. During brain development, there is a shift of NR2B- to NR2A-containing
      NMDARs. Our findings suggest that Pb2+ exposure impairs or delays this
      developmental switch at the level of the synapse. Finally, we show that alter
      expression of NMDAR complexes in the dendritic spine is most likely due to NMDAR
      inhibition, as exposure to the NMDAR antagonist aminophosphonovaleric acid (APV)
      had similar effects as Pb2+ exposure. These data suggest that NMDAR inhibition by
      Pb2+ during synaptogensis alters NMDAR synapse development, which may have
      lasting consequences on downstream signaling.

PMID- 21192973
TI  - Neuropsychological effects of low-level manganese exposure in welders.
AB  - While the neuropsychological effects of high manganese (Mn) exposure in
      occupational settings are well known, the effects of lower levels of exposure are
      less understood. In this study, we investigated the neuropsychological effects of
      lower level occupational Mn exposure in 46 male welders (mean age=37.4, S.D.=11.7
      years). Each welders' cumulative Mn exposure indices (Mn-CEI) for the past 12
      months and total work history Mn exposure were constructed based on air Mn
      measurements and work histories. The association between these exposure indices
      and performance on cognitive, motor control, and psychological tests was
      examined. In addition, among a subset of welders (n=24) who completed the tests
      both before and after a work shift, we examined the association between cross
      shift Mn exposure assessed from personal monitoring and acute changes in test
      scores. Mn exposures in this study (median=12.9 MUg/m3) were much lower, as
      compared to those observed in other similar studies. Increasing total Mn-CEI was
      significantly associated with slower reaction time on the continuous performance
      test (CPT; p<0.01), as well as worse mood for several scales on the Profile of
      Mood States (POMS; confused, tired, and a composite of tired and energetic, all p
      <= 0.03). Increasing Mn-CEI over the previous 12 months was significantly
      associated with worse mood on the sad, tense, and confused POMS scales (all p <=
      0.03) and the association with worse CPT performance approached significance
      (p=0.10). Higher Mn exposure over the course of a workday was associated with
      worse performance on the CPT test across the day (p=0.06) as well as declines in
      fine motor control over the work-shift (p=0.04), adjusting for age and time
      between the 2 tests. Our study suggests that even at relatively low Mn exposure
      levels neuropsychological effects may manifest particularly with respect to
      attention, mood, and fine motor control.

PMID- 21192974
TI  - On the estimation of the direction of information flow in networks of dynamical
      systems.
AB  - The inference of the interaction structure in networks of dynamical systems
      promises novel insights into the functioning or malfunctioning of systems in the
      neurosciences. This may improve the understanding of mechanisms underlying
      several diseases like tremor disorders and might eventually help to cure
      patients. Of particular interest is the estimation of the direction of
      information flow for which different methods have been suggested and have been
      applied to data from human tremor. Based on a simulated system motivated by the
      human tremor application we analyze the performance of three methods. The
      abilities and limitations of the individual techniques are compared and
      discussed. An application to essential tremor complements this investigation.

PMID- 21192975
TI  - An efficient in vivo method for the isolation of Puumala virus in Syrian hamsters
      and the characterization of the isolates from Russia.
AB  - Puumala virus (PUUV) and other Arvicolinae-borne hantaviruses are difficult to
      cultivate in cell culture. To isolate these hantaviruses efficiently, hantavirus
      nucleocapsid protein (NP)-positive but seronegative wild rodents were selected by
      NP-detection ELISA. Three of 68 Myodes glareolus captured in Samara, Russia, were
      NP-positive and seronegative. Syrian hamsters were inoculated with lung
      homogenates from NP-positive rodents for virus propagation. Virus isolation in
      vitro was carried out by inoculation of lung homogenates of NP-positive hamsters
      to Vero E6 cell monolayers. Two PUUV strains (Samara49/CG/2005 and
      Samara94/CG/2005) from M. glareolus were isolated in Vero E6 cells. Nucleotide
      and amino acid sequence identities of the S segment of these isolates to those of
      PUUV F-s808 from a fatal HFRS patient in Samara region were 96.7-99.3% and 99.3
      100.0%, respectively. Morphologic features of Vero E6 cells infected with PUUV
      strain Samara49/CG/2005 were quite similar to those of Hantaan virus-infected
      cells. Isolation of Hokkaido virus from Myodes rufocanus captured in Hokkaido,
      Japan, was also performed. Hokkaido virus NP and RNA were recovered and
      maintained in hamsters. These results suggest that inoculation of Syrian hamsters
      with rodent samples is an efficient method for the isolation and maintenance of
      PUUV and other Arvicolinae-borne hantaviruses.

PMID- 21192976
TI  - Evaluation of the time resolved fluorescence immunoassay (TRFIA) for the
      detection of varicella zoster virus (VZV) antibodies following vaccination of
      healthcare workers.
AB  - Determination of varicella zoster virus (VZV) immunity in healthcare workers
      without a history of chickenpox is important for identifying those in need of
      vOka vaccination. Post immunisation, healthcare workers in the UK who work with
      high risk patients are tested for seroconversion. To assess the performance of
      the time-resolved fluorescence immunoassay (TRFIA) for the detection of antibody
      in vaccinated as well as unvaccinated individuals, a cut-off was first
      calculated. VZV-IgG specific avidity and titres six weeks after the first dose of
      vaccine were used to identify subjects with pre-existing immunity among a cohort
      of 110 healthcare workers. Those with high avidity (>= 60%) were considered to
      have previous immunity to VZV and those with low or equivocal avidity (<60%) were
      considered naive. The former had antibody levels >= 400 mIU/mL and latter had
      levels < 400 mIU/mL. Comparison of the baseline values of the naive and immune
      groups allowed the estimation of a TRFIA cut-off value of > 130 mIU/mL which best
      discriminated between the two groups and this was confirmed by ROC analysis.
      Using this value, the sensitivity and specificity of TRFIA cut-off were 90% (95%
      CI 79-96), and 78% (95% CI 61-90) respectively in this population. A subset of
      samples tested by the gold standard Fluorescence Antibody to Membrane Antigen
      (FAMA) test showed 84% (54/64) agreement with TRFIA.

PMID- 21192977
TI  - Rapid HIV tests in acute care settings in an area of low HIV prevalence in
      Canada.
AB  - Rapid HIV testing has the potential to improve medical care and reduce the
      transmission of infection. In this study, rapid HIV testing was performed on
      serum samples in acute care settings in five hospitals from urban and rural
      regions using the INSTITM HIV-1/HIV-2 Rapid Antibody Test (bioLytical
      Laboratories, Richmond, British Columbia). Parallel standard HIV antibody tests
      were performed at the provincial reference laboratory. Patient demographics,
      indication for testing and risk behaviours were collected. From April 30, 2007
      and November 23, 2009, 1708 individuals were tested: 875 (50.3%) tests in
      pregnant women, 730 (42%) in source individuals in blood and body fluid exposures
      and 119 (5.8%) in acutely ill persons. Twenty-five (1.4%) samples were reactive
      by rapid HIV testing, of which 13 were reactive previously and 1 was a false
      reactive. Sensitivity of the rapid HIV test compared to standard HIV testing was
      100%, specificity was 99.9%, the positive predictive value was 96% and the
      negative predictive value was 100%. The median time from specimen collection to
      availability of the rapid HIV result varied by site and ranged from 54 min to 1h
      42 min. In this study, the INSTITM HIV-1 Rapid Antibody test identified reactive
      and non-reactive samples with similar accuracy to the conventional testing
      algorithm and provided a reliable way to perform rapid HIV testing in acute care
      settings.

PMID- 21192978
TI  - Partial deletion in the spike endodomain of mouse hepatitis virus decreases the
      cytopathic effect but maintains foreign protein expression in infected cells.
AB  - Mouse hepatitis virus (MHV) produces a series of subgenomic RNAs for viral
      protein expression. As a prototype coronavirus, MHV has been explored extensively
      and is often used to express foreign proteins. Previously, a 13-residue deletion
      in the MHV spike (S) protein endodomain was found to reduce syncytium formation
      dramatically while inhibiting virus replication slightly. In this study, the
      effects of the S mutation on MHV infectivity and foreign protein expression were
      further examined in rat or mouse L2, NIH/3T3 and Neuro-2a cells. The replacement
      of the MHV 2a/haemagglutinin-esterase gene with a membrane-anchored protein hook
      (HK) and replacement of gene 4 with EGFP did not change the adaptability and
      cytopathology of recombinant viruses in these cells. However, the cytopathic
      effect of the recombinants with the partial S deletion was reduced significantly
      in these cells. The replication and foreign protein expression of the S-mutated
      recombinants were found to be more efficient in L2 cells than in Neuro-2a and
      NIH/3T3 cells. Meanwhile, the distribution patterns of HK and EGFP expressed by
      the recombinant viruses were similar to those in cells transfected with a
      eukaryotic expression vector. These results suggest that the partial deletion in
      the S endodomain may increase the usefulness of MHV as a viral vector by
      attenuation and maintaining foreign protein expression.

PMID- 21192979
TI  - Detection and differentiation of virulent and avirulent strains of Newcastle
      disease virus by real-time PCR.
AB  - A rapid diagnostic method based on the melting curve SYBR Green I real-time PCR
      analysis was developed to detect and differentiate Newcastle disease virus (NDV)
      strains. Degenerated primers based on the cleavage site sequence of the F0 gene
      were designed to detect specific sequences characteristic of virulent and
      avirulent strains of NDV. Eighteen strains of NDV from four lineages were
      identified and grouped into virulent and avirulent strains. Peaks on the melting
      temperature graph with melting temperature values between 80.00 and 83.80 degrees
      C were observed for lentogenic (avirulent) strains. T(m) values higher than 83.80
      were observed for virulent (mesogenic and velogenic) strains. The detection limit
      of real-time PCR was 2 * 10(2) plasmid copies per reaction or 10(2) EID(50) for
      velogenic strains and 10(3) EID(50) for lentogenic strains. The results obtained
      in this study demonstrate the possible applications for melting curve real-time
      PCR analysis in laboratory practice for the diagnosis and differentiation of
      avirulent and virulent strains of Newcastle disease virus.

PMID- 21192980
TI  - Multiplication of Taura syndrome virus in primary hemocyte culture of shrimp
      (Penaeus vannamei).
AB  - The propagation of Taura syndrome virus (TSV) in primary hemocyte culture of
      Pacific white shrimp (Penaeus vannamei) was investigated. Purified TSV was
      inoculated into a 24 h old primary hemocyte culture and the development of
      cytopathic effects was monitored. The cell morphology started changing within 6 h
      post-inoculation; TSV-infected hemocytes started shrinking and granular
      structures began to form on the cell surface. There was a gradual loss of cell
      viability and, by 48 h post-inoculation, most cells detached from the bottom of
      the 96 well microplate. The propagation of TSV during the 48 h time course
      studied was measured by real-time RT-PCR. TSV copy number reached the highest
      level by 12 h post-inoculation and then started to decrease. Using an anti-TSV
      polyclonal antibody, the 55 kDa VP1 capsid protein was detected by Western blot
      analysis. The data suggest that shrimp primary hemocyte culture supports TSV
      replication and could be used as a tool for the study of host-virus interactions
      in TSV pathogenesis.

PMID- 21192981
TI  - Norovirus 3rd Generation kit: an improvement for rapid diagnosis of sporadic
      gastroenteritis cases and valuable for outbreak detection.
AB  - The aim of this study was to evaluate the sensitivity and specificity of the
      Ridascreen((r)) Norovirus 3rd Generation kit compared to the RT-PCR. A
      retrospective, descriptive study was conducted with 245 specimens from sporadic
      cases and outbreak surveillance samples of gastroenteritis in Brazil from 2006 to
      2009. Overall, the kit showed a sensitivity of 61.8% and a specificity of 92.5%.
      The sensitivity for outbreaks diagnosis was 87.9% and specificity 83.8%. The
      Ridascreen((r)) 3rd Generation could detect specimen containing genogroup (G) II
      with high sensitivity. However, GI and mixed infections (GI/GII) were unlikely to
      be detected by the kit. ELISA for Norovirus (NoV) detection provides a rapid,
      technically simple assay system that can be used to increase the surveillance of
      gastroenteritis outbreaks, especially in Public Health Laboratories with high
      sample throughput. This assay is useful for the detection of NoV outbreaks and is
      an improvement as compared to previous ELISAs; however, due to its sensitivity,
      RT-PCR in still required for routine NoV detection in sporadic cases
      investigation.

PMID- 21192982
TI  - A type-specific blocking ELISA for the detection of infectious bronchitis virus
      antibody.
AB  - Infectious bronchitis virus (IBV) infection has been a major threat to the
      poultry industry worldwide. Current commercially available ELISA kits detect
      group-specific antibodies; however, to understand the status of field infection,
      a monoclonal antibody (mAb) blocking ELISA (b-ELISA) against local IBVs was
      developed. The selected mAb showed specificity to Taiwan IBV strains but had no
      cross-reactivity with the vaccine strain H120. Using the hemagglutination
      inhibition (HI) test as a standard, the cut-off value, sensitivity, and
      specificity of a b-ELISA using this mAb were evaluated in 390 field samples. The
      type-specificity of detection was validated using a panel of chicken hyperimmune
      sera. The results showed that the b-ELISA demonstrated high sensitivity (98.0%)
      and specificity (97.2%) of detection. The agreement between the results of the b
      ELISA and the HI test was statistically significant (Kappa=0.95), and there was
      no significant difference between these two methods (McNemar p=0.72). The b-ELISA
      specifically detected Taiwan IBV serotypes but not three non-Taiwan IBV serotypes
      nor sera against other avian pathogens. This b-ELISA provides type-specific
      antibody detection of local IBV strains. It has the potential to serve as a rapid
      and reliable diagnostic method for IBV clinical infections in the field in
      Taiwan.

PMID- 21192983
TI  - A multiplex RT-PCR for rapid and simultaneous detection of porcine teschovirus,
      classical swine fever virus, and porcine reproductive and respiratory syndrome
      virus in clinical specimens.
AB  - A multiplex RT-PCR (mRT-PCR) assay was developed and evaluated for its ability to
      detect multiple viral infections of swine simultaneously. One pair of primers was
      selected carefully for each of the following three RNA viruses: porcine
      reproductive and respiratory syndrome virus (PRRSV), classical swine fever virus
      (CSFV), and porcine teschovirus (PTV). Each target produced a specific amplicon
      with a size of 451bp (PRRSV), 343bp (CSFV), or 163bp (PTV). The sensitivity of
      the mRT-PCR using purified plasmid constructs containing the specific viral
      target fragments was 2.02 x 102, 2.90 x 103, and 6.16 x 103 copies for PRRSV,
      CSFV, and PTV, respectively. Among 69 clinical samples from Heilongjiang, Jilin,
      and Henan provinces, co-infection by PRRSV and CSFV was 4.4%, co-infection by
      PRRSV and PTV was 11.6%, co-infection by PTV and CSFV was 13.0%, and co-infection
      by the three viruses was 8.7%. In conclusion, the mRT-PCR should be useful for
      routine molecular diagnosis and epidemiology.

PMID- 21192984
TI  - Treadmill exercise prevents decline in spatial learning and memory in APP/PS1
      transgenic mice through improvement of hippocampal long-term potentiation.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease clinically
      characterized by learning and memory function deterioration. While it is well
      established that exercise can improve cognitive performance in AD, there have
      been few basic cellular and molecular mechanisms research performed to test the
      interaction between exercise and AD. In this study, we aimed at investigating
      whether treadmill exercise improves learning and memory function in APP/PS1
      transgenic mouse model of Alzheimer's disease by enhancing long-term potentiation
      (LTP) and up-regulation of brain-derived neurotrophic factor (BDNF) mRNA
      expression. Our results show that, in comparison to wild type mice, transgenic
      mice were characterized by impaired learning and memory function, LTP deficits
      and increased BDNF mRNA levels. Treadmill exercise enhanced learning and memory
      function not only in wild type mice but also in APP/PS1 mice paralleled by LTP.
      However, BDNF has emerged as a crucial regulator of synaptic plasticity
      mechanisms underlying learning and memory in wild-type mice, but not in APP/PS1
      mice. Hence, this investigation demonstrates that treadmill exercise is an
      effective therapeutic that alleviate learning and memory decline in APP/PS1 mouse
      model, and enhanced LTP maybe a cellular mechanism involved in neuropathological
      course of AD and cognitive improvement induced by exercise.

PMID- 21192985
TI  - Chronic omega-3 fatty acids supplementation promotes beneficial effects on
      anxiety, cognitive and depressive-like behaviors in rats subjected to a restraint
      stress protocol.
AB  - Recent evidence has demonstrated dietary influence on the manifestation of
      different types of behaviors induced by stressor tasks. The present study
      examined the impact of omega-3 polyunsaturated fatty acids (PUFAs)
      supplementation in an early phase of the brain development with the goal of
      preventing or even attenuating the occurrence of stress-related behaviors such as
      depressive-like behaviors, anxiety and cognitive dysfunctions in male rats
      subjected to restraint stress. Our results indicated that the supplementation
      regimen successfully counteracted the anxiogenic effects of stress as evidenced
      by the rats' increased exploration time in the aversive arms of the elevated plus
      maze. The forced swimming test indicated that immobility and swimming were more
      deeply influenced by PUFAs supplementation, thereby demonstrating an
      antidepressant effect. Furthermore, cognitive function was shown to be intensely
      affected by restraint stress, but the effects were surprisingly counteracted by
      the PUFAs supplementation. Lastly, plasmatic corticosterone levels were
      demonstrated to be drastically increased by the restraint stress; however, PUFAs
      supplementation promoted a reduction of this stress-related hormone to levels
      that were comparable to those observed in the control group. Our results
      suggested that the mechanisms underlying these effects are possibly associated
      with the reduction of corticosterone levels promoted by the PUFAs supplementation
      in the stress-induced animals. Further studies to examine the participation of
      PUFAs in mediating different behaviors in rats subjected to restraint stress are
      warranted.

PMID- 21192987
TI  - Influence of transgenic corticotropin-releasing factor (CRF) over-expression on
      social recognition memory in mice.
AB  - We examined juvenile social recognition and discrimination in mice with early
      post-natal onset, transgenic CRF over-expression (CRF-OE) and in their wild-type
      littermates (WT). CRF-OE mice showed enhanced social investigation during the
      first encounter, normal short-term and facilitated long-term social recognition
      memory, compared to WT. These results suggest that chronically elevated brain CRF
      tone may contribute in better remembering ethologically relevant and emotionally
      salient stimuli, such as social interaction.

PMID- 21192986
TI  - Brain enlargement and increased behavioral and cytokine reactivity in infant
      monkeys following acute prenatal endotoxemia.
AB  - Infections and inflammatory conditions during pregnancy can dysregulate neural
      development and increase the risk for developing autism and schizophrenia. The
      following research utilized a nonhuman primate model to investigate the potential
      impact of a mild endotoxemia during pregnancy on brain maturation and behavioral
      reactivity as well as the infants' hormone and immune physiology. Nine pregnant
      female rhesus monkeys (Macaca mulatta) were administered nanogram concentrations
      of lipopolysaccharide (LPS) on two consecutive days, 6 weeks before term, and
      their offspring were compared to nine control animals. When tested under arousing
      challenge conditions, infants from the LPS pregnancies were more behaviorally
      disturbed, including a failure to show a normal attenuation of startle responses
      on tests of prepulse inhibition. Examination of their brains at 1 year of age
      with magnetic resonance imaging (MRI) revealed the unexpected finding of a
      significant 8.8% increase in global white matter volume distributed across many
      cortical regions compared to controls. More selective changes in regional gray
      matter volume and cortical thickness were noted in parietal, medial temporal, and
      frontal areas. While inhibited neural growth has been described previously after
      prenatal infection and LPS administration at higher doses in rodents, this low
      dose endotoxemia in the monkey is the first paradigm to produce a neural
      phenotype associated with augmented gray and white matter growth.

PMID- 21192988
TI  - Development of Prevotella intermedia-specific PCR primers based on the nucleotide
      sequences of a DNA probe Pig27.
AB  - The aim of this study was to develop Prevotella intermedia-specific PCR primers
      based on the P. intermedia-specific DNA probe. The P. intermedia-specific DNA
      probe was screened by inverted dot blot hybridization and confirmed by Southern
      blot hybridization. The nucleotide sequences of the species-specific DNA probes
      were determined using a chain termination method. Southern blot analysis showed
      that the DNA probe, Pig27, detected only the genomic DNA of P. intermedia
      strains. PCR showed that the PCR primers, Pin-F1/Pin-R1, had species-specificity
      for P. intermedia. The detection limits of the PCR primer sets were 0.4pg of the
      purified genomic DNA of P. intermedia ATCC 49046. These results suggest that the
      PCR primers, Pin-F1/Pin-R1, could be useful in the detection of P. intermedia as
      well as in the development of a PCR kit in epidemiological studies related to
      periodontal diseases.

PMID- 21192989
TI  - An atomic force microscopy method for the detection of binding forces between
      bacteria and a lipid bilayer containing higher order gangliosides.
AB  - We developed an atomic force microscopy (AFM) method to determine the binding
      forces between a model cell wall plasma membrane and Vibrio cholerae. V. cholerae
      cells were covalently attached to AFM probes and forces were determined against a
      lipid bilayer containing sialic acid (N-acetylneuraminic acid) molecules as well
      as several control surfaces.

PMID- 21192990
TI  - Uni-directional differentiation of mouse embryonic stem cells into neurons by the
      neural stem sphere method.
AB  - We previously showed that our neural stem sphere (NSS) method promotes the
      neuronal differentiation of mouse, monkey and human embryonic stem (ES) cells.
      Here we analyzed changes in expression of marker genes and proteins during
      neuronal differentiation. When cultured in astrocyte-conditioned medium (ACM)
      under free-floating conditions, colonies of ES cells formed floating cell
      spheres, which, within 4 days, gave rise to NSSs. In the spheres, the expression
      of ES cell marker genes was consistently down-regulated, while expression of an
      epiblast marker was transiently up-regulated, beginning on day 2, and the
      expression of neuroectoderm, neural stem cell and neuron markers was up
      regulated, beginning on days 3, 4 and 6, respectively. The expression of the
      marker genes was consistent with that of marker proteins. The time course of
      expression of these markers in the spheres resembled that of neuronal
      differentiation from the inner cell mass (ICM) cells of blastula. In contrast,
      the expression of endoderm, mesoderm, epidermis, astrocyte and oligodendrocyte
      markers was low and not up-regulated during differentiation. Only a small number
      of apoptotic cells were present in the spheres. These results suggest that mouse
      ES cells uni-directionally differentiate into neurons via epiblast cells,
      neuroectodermal cells and neural stem cells.

PMID- 21192991
TI  - Olfactory ensheathing cells as putative host cells for Streptococcus pneumoniae:
      evidence of bacterial invasion via mannose receptor-mediated endocytosis.
AB  - Olfactory ensheathing cells (OECs) are a special glia that ensheath olfactory
      receptor axons that enter the brain via olfactory phila, thus, providing a
      potential route for access of pathogens. Streptococcus pneumoniae (Sp), that has
      a capsule rich in mannosyl residues, is the most common cause of rhinosinusitis
      that may evolve to meningitis. We have tested whether OECs in vitro express the
      mannose receptor (MR), and could internalize Sp via MR. Cultures were infected by
      a suspension of Sp (ATCC 49619), recognized by an anti-Sp antibody, in a 100:1
      bacteria:cells ratio. Competition assays, by means of mannan, showed around a 15
      fold reduction in the number of internalized bacteria. To verify whether MR could
      be involved in Sp uptake, OECs were reacted with an antibody against the MR C
      terminal peptide (anti-cMR) and bacteria were visualized with Sytox Green.
      Selective cMR-immunoreaction was seen in perinuclear compartments containing
      bacteria whereas mannan-treated cultures showed an extremely low percentage of
      internalized bacteria and only occasional adhered bacteria. Our data suggest the
      involvement of MR in adhesion of bacteria to OEC surface, and in their
      internalization. Data are also coherent with a role of OECs as a host cell prior
      to (and during) bacterial invasion of the brain.

PMID- 21192992
TI  - Development of targeted recombinant polymers that can deliver siRNA to the
      cytoplasm and plasmid DNA to the cell nucleus.
AB  - One of the major limitations to effective siRNA delivery is the lack of a siRNA
      specific delivery system. Currently, the same delivery systems that are used for
      plasmid DNA (pDNA) delivery to the cell nucleus are used for siRNA delivery to
      the cytoplasm. To fill this gap, the objective of this study was to design a
      biopolymer that can be programmed via its amino acid sequence to deliver siRNA
      specifically to cytoplasm. For pDNA delivery, a nuclear localization signal (NLS)
      was added to the biopolymer structure to facilitate active translocation of the
      genetic material towards nucleus. The biopolymers were complexed with pEGFP and
      GFP-siRNA and used to transfect SKOV-3 (HER2+) cells. The intracellular
      trafficking of the nanoparticles was also monitored in real-time and live cells.
      The results demonstrated that the biopolymer with NLS is a suitable carrier for
      pDNA delivery but not siRNA delivery. Conversely, the biopolymer without NLS was
      suitable for siRNA delivery to the cytoplasm but not pDNA to the cell nucleus.
      The potential use of the designed biopolymer for combination therapy of cancer
      cells with gene (thymidine kinase) and siRNA (BCL2) was also examined in SKOV-3
      cancer cells.

PMID- 21192993
TI  - Systemic gene transfer of polyethylenimine (PEI)-plasmid DNA complexes to
      neonatal mice.
AB  - Non-viral vectors have not been extensively investigated in neonatal mice due to
      the poor efficiency of the delivery methods available. Understanding the effects
      of non-viral vectors during early development is vital to develop safe gene
      therapy treatments where irreversible pathological processes may be avoided by
      early gene reconstitution. Here we describe a simple and effective method for the
      systemic administration of non-viral vectors via the superior temporal vein of
      mouse pups at 1.5 days of age. We show that injection of polyethylenimine (PEI)
      complexed plasmid DNA (pDNA) intravenously results in effective transfection in
      the liver, lung, heart, spleen, brain and kidney. We also investigate the
      specific targeting of transgene expression to the proliferating neonate liver
      using a liver-specific plasmid containing a Scaffold Matrix Attachment Region
      (S/MAR) element, which has previously been shown to confer long-term expression
      in adult mouse liver. Using bioluminescent imaging, a gradual increase in
      transgene expression was observed which peaked at days 11-12, before the
      reduction of expression to background levels by day 25, suggestive of vector copy
      number loss. We conclude that non-viral vectors can successfully be used for
      systemic delivery to neonatal mice and that this technique is likely to open a
      host of early therapeutic possibilities for gene transfer by a range of non-viral
      vector formulations.

PMID- 21192994
TI  - Satiety. Let's put claims in the right context. Comment on 'Satiety. No way to
      slim'.
AB  - There are several as-yet unresolved issues with the scientific substantiation and
      communication of product claims relating to satiety. Core issues include the
      context, meaning and scope of these claims, and thus the type of clinical
      evidence required to support them. In particular, there are a range of potential
      consumer use-contexts for products carrying these claims, which may not
      necessarily demand evidence of direct effects on weight loss or even energy
      intake. By conflating satiety and 'slimming' claims, and misrepresenting or
      deriding wider views in the field, Booth & Nouwen unfortunately obscure rather
      than bring light to the discussion of these important issues.

PMID- 21192995
TI  - Is food-related lifestyle (FRL) able to reveal food consumption patterns in non
      Western cultural environments? Its adaptation and application in urban China.
AB  - Research related to food-related behaviour in China is still scarce, one reason
      being the fact that food consumption patterns in East Asia do not appear to be
      easily analyzed by models originating in Western cultures. The objective of the
      present work is to examine the ability of the food related lifestyle (FRL)
      instrument to reveal food consumption patterns in a Chinese context. Data were
      collected from 479 respondents in 6 major Chinese cities using a Chinese version
      of the FRL instrument. Analysis of reliability and dimensionality of the scales
      resulted in a revised version of the instrument, in which a number of dimensions
      of the original instrument had to be omitted. This revised instrument was tested
      for statistical robustness and used as a basis for the derivation of consumer
      segments. Construct validity of the instrument was then investigated by profiling
      the segments in terms of consumer values, attitudes and purchase behaviour, using
      frequency of consumption of pork products as an example. Three consumer segments
      were identified: concerned, uninvolved and traditional. This pattern replicates
      partly those identified in Western cultures. Moreover, all three segments showed
      consistent value-attitude-behaviour profiles. The results also suggest which
      dimensions may be missing in the instrument in a more comprehensive instrument
      adapted to Chinese conditions, most notably a broader treatment of eating out
      activities.

PMID- 21192996
TI  - Satiety and body weight control. Promise and compromise. Comment on 'Satiety. No
      way to slim'.
AB  - Satiety is a complex psycho-physiological mechanism that allows the adjustment of
      energy intake to expenditures. As such, it plays an important role among the
      numerous interacting mechanisms contributing to body weight control. Booth and
      Nouwen rightfully stress that satiety claims can be misleading and even dangerous
      when they are misrepresented or misinterpreted as slimming claims. Indeed, a
      substance that might enhance satiety, especially by affecting sensations on the
      short term, will not necessarily help to decrease energy intake on the longer
      term or facilitate weight loss. While denouncing abusive claims, the article by
      Booth and Nouwen also refers to numerous contributions of satiety mechanisms that
      could potentially affect intake and weight control over the long term. We propose
      that multi-step proofs of concepts could be useful in this field. Satiety effects
      are one early step in a complex demonstration of how a substance could affect
      short-term intake, hormonal mechanisms, and medium or long term changes in body
      weight. An example of such a step-wise process is described (beneficial effects
      of calcium and dairy products on appetite and weight change). Booth and Nouwen
      insist that satiety effects should be evaluated in the context of the local socio
      cultural meal pattern and lifestyle. This wise advice supports the use of multi
      step proofs of concept, perhaps including the use of biomarkers as well as
      behavioural measures, before any satiety enhancement claim can be considered to
      have any actual impact on body weight control.

PMID- 21192997
TI  - Consumers' purchase of organic food products. A matter of convenience and
      reflexive practices.
AB  - The aim of this study was to gain insight into the purchase of organic food
      products by consumers and to explore the main factors driving this process. This
      paper uses evidence from 16 in-depth interviews with consumers in Denmark carried
      out in 2008-2009. On the basis of the analysis two broad concepts are suggested:
      convenience behaviours and reflexive practices. Convenience behaviours are
      characteristic of pragmatic organic consumers. This type of shopping behaviour
      requires organic foods to be available in the local supermarket, they have to be
      clearly visible (preferably with an eco-label), and the price differential vis-a
      vis conventional products have to be minimal. The analysis also showed that
      politically/ethically minded consumers have reflexive practices when purchasing
      organic food products: health considerations, ethical considerations (animal
      welfare), political considerations (environmentalism) and quality considerations
      (taste) play an important part for these consumers. Reflexive shopping practices
      can be sparked by life events (e.g. having children), "shocking" news about
      conventional food products and similar events, and news capable of creating a
      "cognitive dissonance" among consumers. The Danish case illustrates that the
      government needs to actively implement reforms and promote activities which make
      organic products a convenient choice for the pragmatic oriented consumer if their
      market share is to increase substantially.

PMID- 21192998
TI  - The role of time on task performance in modifying the effects of gum chewing on
      attention.
AB  - Recent research examined the effects of chewing gum on attention and reported a
      significant interaction of gum chewing with time. Using a crossover within
      subject design, the present study examined the effect of gum chewing on sustained
      attention in healthy adults over a period of 30 min. The results revealed a
      significant main effect of time and a significant interaction between gum chewing
      and time. The findings suggest that gum chewing differentially affects attention
      performance. While gum chewing has detrimental effects on sustained attention in
      earlier stages of the task, beneficial effects on sustained attention were
      observed at later stages.

PMID- 21192999
TI  - A chimeric peptide of intestinal trefoil factor containing cholesteryl ester
      transfer protein B cell epitope significantly inhibits atherosclerosis in rabbits
      after oral administration.
AB  - Vaccination against cholesteryl ester transfer protein (CETP) is proven to be
      effective for inhibiting atherosclerosis in animal models. In this study, the
      proteases-resistant intestinal trefoil factor (TFF3) was used as a molecular
      vehicle to construct chimeric TFF3 (cTFF3) containing CETP B cell epitope and
      tetanus toxin helper T cell epitope. It was found that cTFF3 still preserved a
      trefoil structure, and can resist proteases digestion in vitro. After oral
      immunization with cTFF3, the CETP-specific IgA and IgG could be found in
      intestine lavage fluid and serum, and the anti-CETP antibodies could inhibit
      partial CETP activity to increase high-density lipoprotein cholesterol, decrease
      low-density lipoprotein cholesterol, and inhibit atherosclerosis in animals.
      Therefore, TFF3 is a potential molecular vehicle for developing oral peptide
      vaccines. Our research highlights a novel strategy for developing oral peptide
      vaccines in the future.

PMID- 21193000
TI  - Identification and characterization of antimicrobial peptides from the skin of
      the endangered frog Odorrana ishikawae.
AB  - The endangered anuran species, Odorrana ishikawae, is endemic to only two small
      Japanese Islands, Amami and Okinawa. To assess the innate immune system in this
      frog, we investigated antimicrobial peptides in the skin using artificially bred
      animals. Nine novel antimicrobial peptides containing the C-terminal cyclic
      heptapeptide domain were isolated on the basis of antimicrobial activity against
      Escherichia coli. The peptides were members of the esculentin-1 (two peptides),
      esculentin-2 (one peptide), palustrin-2 (one peptide), brevinin-2 (three
      peptides) and nigrocin-2 (two peptides) antimicrobial peptide families. They were
      named esculentin-1ISa, esculentin-1ISb, esculentin-2ISa, palustrin-2ISa, brevinin
      2ISa, brevinin-2ISb, brevinin-2ISc, nigrocin-2ISa and nigrocin-2ISb. Peptide
      primary structures suggest a close relationship with the Asian odorous frogs,
      Odorrana grahami and Odorrana hosii. These antimicrobial peptides possessed a
      broad-spectrum of growth inhibition against five microorganisms (E. coli,
      Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus subtilis and
      Candida albicans). Nine different cDNAs encoding the precursor proteins were also
      cloned and showed that the precursor proteins exhibited a signal peptide, an N
      terminal acidic spacer domain, a Lys-Arg processing site and an antimicrobial
      peptide at the C-terminus.

PMID- 21193001
TI  - Distinct systemic distribution of salusin-alpha and salusin-beta in the rat.
AB  - Salusin-alpha and salusin-beta are multifunctional bioactive peptides that were
      initially predicted using in silico analyses. These peptides should be
      concomitantly biosynthesized from prosalusin in humans. However, little
      information is available yet on the biosynthesis and mode of presence of salusin
      alpha and salusin-beta in non-human species. In the present study, we examined
      whether salusin-alpha and salusin-beta are conserved in the rat and whether
      salusin-alpha and salusin-beta show distinct systemic distributions.
      Immunohistochemical analysis of rat tissues using a specific anti-rat salusin
      alpha antibody detected immunoreactivity extensively in neuronal cells and
      fibers, and abundantly in the epithelial tissues throughout the organs. This
      distribution contrasts sharply with that of salusin-beta, which is mainly
      localized to the neuroendocrine and hematopoietic systems. Western blot analysis
      of rat spleen extracts showed the presence of cleaved fragments corresponding to
      putative rat salusin-alpha. Reverse-phase and gel filtration high performance
      liquid chromatography analyses coupled with radioimmunoassay detection of rat
      urine extracts revealed a major immunoreactive component that co-eluted with
      synthetic putative rat salusin-beta. These data support the processing of rat
      prosalusin into salusin-alpha and salusin-beta despite absent dibasic amino acids
      between the two.

PMID- 21193002
TI  - Release of ATP from avian Muller glia cells in culture.
AB  - ATP can be released from neurons and act as a neuromodulator in the nervous
      system. Besides neurons, cortical astrocytes also are capable of releasing ATP
      from acidic vesicles in a Ca(2+)-dependent way. In the present work, we
      investigated the release of ATP from Muller glia cells of the chick embryo retina
      by examining quinacrine staining and by measuring the extracellular levels of ATP
      in purified Muller glia cultures. Our data revealed that glial cells could be
      labeled with quinacrine, a reaction that was prevented by incubation of the cells
      with 1MUM bafilomycin A1 or 2MUM Evans blue, potent inhibitors of vacuolar
      ATPases and of the vesicular nucleotide transporter, respectively. Either 50mM
      KCl or 1mM glutamate was able to decrease quinacrine staining of the cells, as
      well as to increase the levels of ATP in the extracellular medium by 77% and
      89.5%, respectively, after a 5min incubation of the cells. Glutamate-induced rise
      in extracellular ATP could be mimicked by 100MUM kainate (81.5%) but not by
      100MUM NMDA in medium without MgCl(2) but with 2mM glycine. However, both
      glutamate- and kainate-induced increase in extracellular ATP levels were blocked
      by 50MUM of the glutamatergic antagonists DNQX and MK-801, suggesting the
      involvement of both NMDA and non-NMDA receptors. Extracellular ATP accumulation
      induced by glutamate was also blocked by incubation of the cells with 30MUM BAPTA
      AM or 1MUM bafilomycin A1. These results suggest that glutamate, through
      activation of both NMDA and non-NMDA receptors, induces the release of ATP from
      retinal Muller cells through a calcium-dependent exocytotic mechanism.

PMID- 21193003
TI  - Down-regulation of glutamine synthetase enhances migration of rat astrocytes
      after in vitro injury.
AB  - Astrocytes undergo reactive transformation in response to physical injury
      (reactive gliosis) that may impede neural repair. Glutamine synthetase (GS) is
      highly expressed by astrocytes, and serves a neuroprotective function by
      converting cytotoxic glutamate and ammonia into glutamine. Glutamine synthetase
      was down-regulated in reactive astrocytes at the site of mechanical spinal cord
      injury (SCI) and in cultured astrocytes at the margins of a scratch wound,
      suggesting that GS may modulate reactive transformation and glial scar
      development. We evaluated this potential function of GS using siRNA-mediated GS
      knock-down. Suppression of astrocytic GS by GS siRNA increased cell migration
      into the scratch wound zone and decreased substrate adhesion as indicated by the
      number of focal adhesions expressing the adaptor protein paxillin. Migration was
      enhanced by glutamine and suppressed by glutamate, in contrast to the result
      expected if enhanced migration was due solely to changes in glutamine and
      glutamate concomitant with reduced GS activity. The membrane type 1-matrix
      metalloproteinase (MT1-MMP) was up-regulated in GS siRNA-treated astrocytes,
      while a broad-spectrum MMP antagonist inhibited migration in both wild type and
      GS knock-down astrocytes. In addition, GS siRNA inhibited expression of integrin
      beta1, while antibody-mediated inhibition of integrin beta1 impaired direction
      specific protrusion and motility. Thus, GS may modulate motility and substrate
      adhesion through transmembrane integrin beta1 signaling to the cytoskeleton and
      by MMT-mediated proteolysis of the extracellular matrix.

PMID- 21193004
TI  - Biphasic regulation of tissue plasminogen activator activity in ischemic rat
      brain and in cultured neural cells: essential role of astrocyte-derived
      plasminogen activator inhibitor-1.
AB  - In brain, the serine protease tissue plasminogen activator (tPA) and its
      endogenous inhibitor plasminogen activator inhibitor-1 (PAI-1) have been
      implicated in the regulation of various neurophysiological and pathological
      responses. In this study, we investigated the differential role of neurons and
      astrocytes in the regulation of tPA/PAI-1 activity in ischemic brain. The
      activity of tPA peaked transiently and then decreased in cortex and striatum
      along with delayed induction of PAI-1 in the inflammatory stage after
      MCAO/reperfusion injury. In cultured primary cells, glutamate stimulation
      increased tPA activity in neurons but not in other cells such as microglia and
      astrocytes. With LPS stimulation, a model of neuroinflammatory insults, robust
      PAI-1 induction was observed in astrocytes but not in neurons and microglia. The
      upregulation of PAI-1 by LPS in astrocytes was also verified by RT-PCR analysis
      as well as PAI-1 promoter reporter assay. Lastly, we checked the effects of
      hypoxia on tPA/PAI-1 activity. Hypoxia increased tPA release from neurons without
      effects on microglia, while the activity of tPA in astrocyte was decreased
      consistent with increased PAI-1 activity in astrocyte. Taken together, the
      results from the present study suggest that neurons are the major source of tPA
      and that the glutamate-induced stimulated release is mainly governed by neurons
      in the acute phase. In contrast, the massive up-regulation of PAI-1 in astrocytes
      during subchronic and chronic inflammatory conditions, leads to decreased tPA
      activity in the later stages of MCAO. Differential regulation of tPA and PAI-1 in
      neurons, astrocytes and microglia suggest more attention is required to
      understand the role of local tPA activity in the vicinity of individual cell
      types.

PMID- 21193005
TI  - Bioequivalence evaluation of a triamterene-hydrochlorothiazide generic product: a
      new bioequivalence index for fixed-dose combinations.
AB  - In this study, an open, double-blind, randomized, two-period, two-group crossover
      design was conducted in 14 healthy volunteers to study the bioequivalence of a
      fixed-dose generic product. After administration of test or reference products to
      each volunteer, both active ingredients were determined simultaneously in plasma
      samples using a developed and validated HPLC-UV method, and pharmacokinetic
      parameters, including C(max), T(max), AUC(0-t) , AUC(0infinity), terminal
      elimination rate constant (lambdaz), volume of distribution in steady state
      (Vd(ss)), mean residence time (MRT), clearance (Cl), terminal elimination rate
      constant (Kel) were determined in each subject using the standard non
      compartmental approach. Statistical comparison showed that the test and reference
      products were bioequivalent in terms of both the rate and extent of
      bioavailability of both active ingredients. Finally, a new parameter named range
      overlap index (ROI) was introduced for the first time in this study in order to
      judge about the overall bioequivalence of the combination products. This
      parameter indicates the extent in which the two CI90% ranges of each parameter
      for two active ingredients overlap with each other. The ROI is suggested to be
      equal or more than 50% for two combination products in order to be known as
      bioequivalent. The ROI values of the bioequivalence-indicating parameters were
      61.90%, 84.6%, and 76.0% for C(max), AUC(0--->12), and AUC(0--->infinity),
      respectively, which are indicative for bioequivalence in all the cases.

PMID- 21193006
TI  - Unraveling the biological mechanisms in Alzheimer's disease--lessons from
      genomics.
AB  - Alzheimer's disease (AD) is the most common form of dementia and the most common
      neurodegenerative disease, with a complex genetic background. Genome-wide
      association studies (GWAS) have yielded important new insights into genetic
      mechanisms of AD pathology. Current results unequivocally confirm apolipoprotein
      E (APOE) as a major genetic risk factor for development of late onset AD.
      Additional associations of more than twenty genes have also been identified and
      replicated in subsequent genetic studies. Despite the exciting new GWAS data
      which have emerged in the last few years, it has become clear that common
      variants within the genome cannot fully explain the underlying genetic risk for
      AD. Novel approaches such as genome-wide analysis of copy number variations (CNV)
      or low-frequency rare functional gene variants may provide additional insight
      into genetic basis of AD. In this review we summarize the findings of eighteen
      GWAS studies in AD performed to date, with an emphasis on potential future
      developments in the quest for genetic risk factors of AD.

PMID- 21193007
TI  - Genotypic identification of Penicillium expansum and the role of processing on
      patulin presence in juice.
AB  - This work aimed at isolation and identification of patulin producing fungi and to
      follow the presence of patulin during apple juice processing. Among 34
      Penicillium isolates, eight isolates (five from healthy appeared apples and 12
      from rot spotted apples) were considered as patulin producers using thin-layer
      chromatography. These isolates were classically identified as a Penicillium
      expansum. PCR utilizing primers based on the polygalacturonase gene of P.
      expansum was applied for detecting this mold. The PCR amplified a 404-bp DNA
      product from all tested P. expansum isolates, but not in other common food
      spoilage Penicillium species. RAPD technique using P1 or M13 primers was applied
      to determine the similarity of the P. expansum isolates. RAPD results revealed
      that the tested strains showed high percentage of similarity and no correlation
      was observed between cluster analysis and the sources of isolation. Patulin could
      not be detected in healthy appeared apples and their extracted juice during
      different stages of juice process. In apple juice made from the healthy parts of
      apples decayed by P. expansum contained patulin which may present health hazard.
      The obtained results assured that patulin is known to be stable in apple juice
      even after pasteurization. In conclusion, the removal of the rotten part from the
      fruit is not sufficient to eliminate the mycotoxin patulin from apple juice.
      Although, the enzyme treatment (pectinase and amylase) and pasteurization (95 
      degrees C for 7 min) significantly (p < 0.05) reduced patulin level, its level is
      still higher than the level of <50 MUg/kg considered by Codex alimentarius when
      the apple juice processed from the healthy parts of rot spotted fruits.

PMID- 21193008
TI  - Mercury, cadmium, lead and arsenic levels in three pelagic fish species from the
      Atlantic Ocean: intra- and inter-specific variability and human health risks for
      consumption.
AB  - Three commonly consumed and commercially valuable fish species (sardine, chub and
      horse mackerel) were collected from the Northeast and Eastern Central Atlantic
      Ocean in Portuguese waters during one year. Mercury, cadmium, lead and arsenic
      amounts were determined in muscles using graphite furnace and cold vapour atomic
      absorption spectrometry. Maximum mean levels of mercury (0.1715 +/- 0.0857 mg/kg,
      ww) and arsenic (1.139 +/- 0.350 mg/kg, ww) were detected in horse mackerel. The
      higher mean amounts of cadmium (0.0084 +/- 0.0036 mg/kg, ww) and lead (0.0379 +/-
      0.0303 mg/kg, ww) were determined in chub mackerel and in sardine, respectively.
      Intra- and inter-specific variability of metals bioaccumulation was statistically
      assessed and species and length revealed to be the major influencing biometric
      factors, in particular for mercury and arsenic. Muscles present metal
      concentrations below the tolerable limits considered by European Commission
      Regulation and Food and Agriculture Organization of the United Nations/World
      Health Organization (FAO/WHO). However, estimation of non-carcinogenic and
      carcinogenic health risks by the target hazard quotient and target carcinogenic
      risk, established by the US Environmental Protection Agency, suggests that these
      species must be eaten in moderation due to possible hazard and carcinogenic risks
      derived from arsenic (in all analyzed species) and mercury ingestion (in horse
      and chub mackerel species).

PMID- 21193009
TI  - Preventive effect of piracetam and vinpocetine on hypoxia-reoxygenation induced
      injury in primary hippocampal culture.
AB  - The present study investigates the potential of Piracetam and Vinpocetine
      (nootropic drugs, known to possess neuroprotective properties) in preventing
      hypoxia-reoxygenation induced oxidative stress in primary hippocampal cell
      culture. The hippocampal culture was exposed to hypoxia (95% N(2), 5% CO(2)) for
      3h and followed by 1h of reoxygenation (21% O(2) and 5% CO(2)) at 37  degrees C.
      The primary hippocampal cultures were supplemented with the optimum dose of
      Piracetam and Vinpocetine, independently, and the cultures were divided into six
      groups, viz. Control/Normoxia, Hypoxia, Hypoxia+Piracetam, Hypoxia+Vinpocetine,
      Normoxia + Piracetam and Normoxia+Vinpocetine. The cell-viability assays and
      biochemical oxidative stress parameters were evaluated for each of the six
      groups. Administration of 1mM Piracetam or 500 nM Vinpocetine significantly
      prevents the culture from hypoxia-reoxygenation injury when determined by Neutral
      Red assay, LDH release and Acetylcholine esterase activity. Results showed that
      Piracetam and Vinpocetine supplementation significantly prevented the fall of
      mitochondrial membrane potential, rise in ROS generation and reduction in
      antioxidant levels associated with the hypoxia-reoxygenation injury. In
      conclusion, the present study establishes that both Piracetam and Vinpocetine
      give neuroprotection against hypoxia-reoxygenation injury in primary hippocampal
      cell culture.

PMID- 21193010
TI  - Application of the threshold of toxicological concern (TTC) concept to the safety
      assessment of chemically complex food matrices.
AB  - The toxicological assessment of chemically complex food matrices (CCFM) usually
      is very time consuming, expensive and uses many animal studies. Improvements to
      obtain a more efficient assessment process remain limited as long as we retain
      traditional approaches to toxicological risk assessment. New concepts would be
      needed to achieve real innovations in risk assessment. The threshold of
      toxicological concern (TTC) potentially is such a concept that has existed for
      many years and recently has been further developed. The safety of CCFM is
      difficult to assess as there are numerous unknown substances present (often
      referred to as 'Forest-of-Peaks' in chromatographic analysis). Usually, for the
      evaluation of CCFM, a full safety assessment approach involving animal studies is
      needed, but the exposure to most substances is low and TTC might be applicable.
      However, to apply TTC efficiently to CCFM, a strategy is needed to deal with
      large numbers of unknowns (substances of which structural information is
      lacking). Therefore, we have drafted a framework for application of TTC in safety
      assessment of CCFM. This paper describes the criteria and development of the
      framework proposing a stepwise approach for the application of TTC in safety
      assessment of CCFM and future developments required.

PMID- 21193011
TI  - Melatonin--a pleiotropic, orchestrating regulator molecule.
AB  - Melatonin, the neurohormone of the pineal gland, is also produced by various
      other tissues and cells. It acts via G protein-coupled receptors expressed in
      various areas of the central nervous system and in peripheral tissues. Parallel
      signaling mechanisms lead to cell-specific control and recruitment of downstream
      factors, including various kinases, transcription factors and ion channels.
      Additional actions via nuclear receptors and other binding sites are likely. By
      virtue of high receptor density in the circadian pacemaker, melatonin is involved
      in the phasing of circadian rhythms and sleep promotion. Additionally, it exerts
      effects on peripheral oscillators, including phase coupling of parallel cellular
      clocks based on alternate use of core oscillator proteins. Direct central and
      peripheral actions concern the up- or downregulation of various proteins, among
      which inducible and neuronal NO synthases seem to be of particular importance for
      antagonizing inflammation and excitotoxicity. The methoxyindole is also
      synthesized in several peripheral tissues, so that the total content of tissue
      melatonin exceeds by far the amounts in the circulation. Emerging fields in
      melatonin research concern receptor polymorphism in relation to various diseases,
      the control of sleep, the metabolic syndrome, weight control, diabetes type 2 and
      insulin resistance, and mitochondrial effects. Control of electron flux,
      prevention of bottlenecks in the respiratory chain and electron leakage
      contribute to the avoidance of damage by free radicals and seem to be important
      in neuroprotection, inflammatory diseases and, presumably, aging. Newly
      discovered influences on sirtuins and downstream factors indicate that melatonin
      has a role in mitochondrial biogenesis.

PMID- 21193012
TI  - A novel ENU-generated truncation mutation lacking the spectrin-binding and C
      terminal regulatory domains of Ank1 models severe hemolytic hereditary
      spherocytosis.
AB  - OBJECTIVE: Hereditary spherocytosis (HS) is a heterogeneous group of
      spontaneously arising and inherited red blood cell disorders ranging from very
      mild subclinical cases to severe and life-threatening cases, with symptoms linked
      directly to the severity of the mutation at the molecular level. We investigated
      a novel mouse model in which the heterozygotes present with the diagnostic
      hallmarks of mild HS and surviving homozygotes phenocopy severe hemolytic HS.
      MATERIALS AND METHODS: We used N-ethyl-N-nitrosourea mutagenesis to generate
      random point mutations in the mouse genome and a dominant screen to identify
      mouse models of human hematopoietic disease. Gene mapping of the HS strain
      revealed a unique in-frame nonsense mutation arising from a single base
      transversion in exon 27 of Ank1 (strain designation: Ank1(E924X)). Employing
      conventional hematopoietic, pathological, biochemical, and cell biology assays,
      we characterized heterozygous and homozygous Ank1(E924X) mice at the biochemical,
      cellular, and pathophysiological levels. RESULTS: Although Ank1(E924X/E924X) red
      blood cell ghosts lack abundant full-length ankyrin-1 isoforms, N-terminal
      epitope ankyrin-1 antibodies reveal a band consistent with the theoretical size
      of a truncated mutant ankyrin-1. Using domain-specific antibodies, we further
      show that this protein lacks both a spectrin-binding domain and a C-terminal
      regulatory domain. Finally, using antisera that detect C-terminal residues of the
      products of alternative Ank1 transcripts, we find unique immunoreactive bands not
      observed in red blood cell ghosts from wild-type or Ank1(E924X) heterozygous
      mice, including a band similar in size to full-length ankyrin-1. CONCLUSIONS: The
      Ank1(E924X) strain provides a novel tool to study Ank1 and model HS.

PMID- 21193013
TI  - The juvenile hormone analogue methoprene up-regulates the Ha-RNA-binding protein.
AB  - RNA-binding proteins (RBPs) associate with RNA in cells to form ribonucleoprotein
      (RNP) complexes. The RBPs are involved in various aspects of RNA metabolism, but
      their roles in the juvenile hormone (JH) signaling pathway are not well known. An
      RNA-binding protein (Ha-RBP) was obtained from Helicoverpa armigera, a
      lepidopteran insect, which could be up-regulated by the juvenile hormone analogue
      methoprene at the mRNA level. Immunohistochemistry showed that Ha-RBP was mainly
      distributed in cells where protein synthesis was active, and its knockdown
      decreased the protein levels of JH-responsive genes. Immunocytochemistry showed
      that Ha-RBP was located in both the nucleus and the cytoplasm of normal cells,
      and methoprene could promote the translocation of Ha-RBP from the nucleus to the
      cytoplasm. This process was mediated by the JH receptor candidate HaMet but not
      by the ultraspiracle protein (USP). The knockdown of HaMet by RNAi decreased the
      expression of Ha-RBP and blocked its translocation from the nucleus to the
      cytoplasm. Together these findings indicate that Ha-RBP is involved in the
      juvenile hormone signaling pathway and Met mediates JH signaling by regulating Ha
      RBP translocation from nucleus to cytoplasm, which may allow Ha-RBP to modify
      protein translation.

PMID- 21193014
TI  - Possible involvement of calpain-like activity in normal processing of cellular
      prion protein.
AB  - Time-lapse imaging analysis was previously used to show that spontaneous
      proteolysis of PrP(C), which is fluorescence-labeled at both NH(2)- and COOH
      termini, occurred in mouse neuroblastoma neuro2a (N2a) cells susceptible to
      PrP(Sc). We demonstrated that, unlike other protease inhibitors, a calpain
      inhibitor, calpastatin, drastically inhibited endoproteolysis of PrP(C), as
      observed with time-lapse imaging in living cells, suggesting calpain-like
      activity. Calpastatin also inhibited cleavage of endogenous PrP(C), and
      unprocessed molecules and the double-labeled PrP(C) accumulated around the
      perinuclear region. The molecular weight of PrP(C) fragments generated by
      spontaneous proteolysis was identical to those produced when PrP(C) synthesized
      in vitro was exposed to exogenous calpain. These results suggest that a calpain
      like activity mediates normal processing of PrP(C) in N2a cells.

PMID- 21193015
TI  - A cross-linguistic examination of cortical auditory evoked potentials for a
      categorical voicing contrast.
AB  - Behavioral perceptions and cortical auditory evoked potentials (CAEPs) from
      native English (N=10) and Spanish speakers (N=10) were recorded for speech
      stimuli that constitute phonetically relevant categories of voicing. The stimuli
      were synthesized bilabial stop consonant-vowel syllables in a continuum ranging
      from/ba/to/pa/that varied in voice onset time (VOT) from 0 to 60 ms. Different
      behavioral perceptions were evidenced by significantly different categorical
      phonetic boundaries between the two groups (p<.0001). In contrast, there were no
      significant differences in CAEP component P1, N1, and P2 mean latencies or P1-N1
      and N1-P2 amplitudes between groups (p>.05). Peak P1, N1, and P2 response
      latencies and P1-N1 and N1-P2 amplitudes increased significantly with increasing
      VOTs (p<.0001 and p<.001, respectively). There were no systematic changes in CAEP
      morphology that corresponded to listeners' perceptual categorical boundaries.
      These findings are consistent with the notion that changes in morphology of the
      P1-N1-P2 response are related to acoustical changes in speech sounds and are
      independent of phonetic categorization of voicing cues across language groups.

PMID- 21193016
TI  - Antiglioma effects of a new, low molecular mass, inhibitor of fibroblast growth
      factor.
AB  - Despite the deployment of multimodal therapies involving neurosurgical resection,
      radio- and polychemotherapy, the prognosis for glioblastoma patients remains
      poor. These tumors are pathologically characterized by their associated
      angiogenesis and diffuse brain invasion, processes that are probably closely
      linked to the unfavorable prognosis of this disease. Accordingly, pharmacological
      inhibition of glioblastoma invasion and approaches that impede angiogenesis are
      considered to be promising therapeutic strategies to combat these tumors.
      Nevertheless, the anti-angiogenic therapies for glioblastoma currently available
      are transient and palliative at best. Blocking the effects of fibroblast growth
      factor (FGF) may represent a novel mean of inhibiting the angiogenesis associated
      with glioblastoma, as it mediates the angiogenesis induced by other factors and
      it is an angiogenic factor by itself. In addition, the survival of glioma cells
      and their resistance to chemotherapeutic agents are highly FGF-dependent. We show
      here that a recently described inhibitor of FGF, 2,5-dihydroxyphenyl-sulfonate
      (2,5DHPS, dobesilate), stimulates the apoptosis of tumor cells, inhibits
      glioblastoma invasion and suppresses its associated angiogenesis. Moreover, this
      agent augments the efficiency of chemotherapeutic agents in a rat model of
      orthotopic brain tumor. These results suggest that 2,5DHPS treatment may
      represent a promising therapy for malignant glioma.

PMID- 21193017
TI  - Overlapping representations of numerical magnitude and motion direction in the
      posterior parietal cortex: a TMS-adaptation study.
AB  - The human posterior parietal cortex (PPC) is involved in the encoding of both
      visual motion and numerical magnitude. In non human primates, neurons have been
      found in PPC that are selective for both motion direction and magnitude. Whether
      such neurons also exist in human PPC is not known. Here we investigated this
      hypothesis using state-dependent transcranial magnetic stimulation (TMS).
      Participants were adapted to a specific motion direction (either leftward or
      rightward), after which they performed a magnitude comparison task, with TMS
      applied at the onset of each trial. Our hypothesis was that neurons tuned to
      leftward motion may also be sensitive to small magnitudes and neurons tuned to
      rightward motion may also be sensitive to large magnitudes, a mapping that may
      have developed via spatial attentional mechanisms. Our results supported this
      view by showing that the effect of PPC TMS on small and large numbers depended on
      the motion direction being adapted, thus suggesting that there may be a
      functional overlap in neuronal representations of motion direction and numerical
      magnitude in human PPC.

PMID- 21193019
TI  - Characterization of spinal ganglion neurons in horse (Equus caballus). A
      morphometric, neurochemical and tracing study.
AB  - Spinal ganglion (SG) neurons have been widely described in rodents, and
      classified according to various criteria. On the basis of such studies, many
      features of rodent SG neurons have become benchmarks to classify these cells.
      However, these traits cannot be confirmed in all other species. In the present
      study, horse SG neurons were morphometrically and neurochemically characterized
      by detecting the neuronal markers calcitonin gene-related peptide (CGRP),
      substance P (SP), neuronal nitric oxide synthase (nNOS) and isolectin B4 (IB4)
      from Griffonia simplicifolia. Moreover, spinal cord staining and tracer studies
      were also performed injecting Fast Blue tracer in the ileo-cecal junction. The
      statistical analysis of the histograms related to the cross sectional area of
      dark and light SG neurons confirmed the presence of the categories of small and
      large neurons. The staining methods employed yielded the following results: (1)
      in all triple staining experiments performed, most SG stained neurons were triple
      labeled; (2) SP-IR neurons showed the largest percentages of co-localization with
      the other markers studied; (3) CGRP-IR and IB4-labeled neurons were the SG
      neurons showing the largest percentages of single staining; (4) nNOS-IR neurons
      were more represented in horse SGs than in those from rodents; (5) IB4 was widely
      co-localized with both CGRP and SP. Retrograde tracer investigation combined with
      neurochemical evaluation showed that in horse, contrarily to rodents, IB4-labeled
      neurons are widely involved in visceral innervations. The results obtained from
      the observations of serial stained sections and from a critical analysis of
      triple-labeling experiments allowed us to conclude that (1) most stained SG
      neurons co-expressed IB4-nNOS-CGRP-SP neuronal markers, (2) IB4 is not indicated
      as a marker of non-peptidergic neurons in the horse, (3) horse IB4-labeled
      neurons are widely involved in visceral sensation, (4) differently from rodents,
      horse IB4-, CGRP- and SP-labeled fibers share the same spinal cord level
      terminations.

PMID- 21193020
TI  - Attention deficit induced by blockade of N-methyl D-aspartate receptors in the
      prefrontal cortex is associated with enhanced glutamate release and cAMP response
      element binding protein phosphorylation: role of metabotropic glutamate receptors
      2/3.
AB  - The hypothesis that attention deficits induced by the hypofunction of N-methyl d
      aspartate (NMDA) receptors in the prefrontal cortex (PFC) might be associated
      with increased glutamate release and changes in the phosphorylation of the cyclic
      adenosine monophosphate response element-binding protein on serine 133 (p
      S(133)CREB) was investigated in this study. Infusion of 50 ng/side 3-(R)-2
      carboxypiperazin-4-propyl-1-phosphonic acid ((R)-CPP), a competitive glutamate
      NMDA receptor antagonist, into the medial prefrontal cortex (mPFC) of rats
      performing the five-choice serial reaction time (5-CSRT) task, reduced accuracy
      of visual discrimination (measured by % correct responses) and enhanced
      impulsivity (measured by the number of premature responses) and compulsivity
      (measured by the number of perseverative responses). The mGluR2/3 receptor
      agonist, LY379268, injected s.c. at 0.1 mg/kg, reduced (R)-CPP-induced impairment
      in attentional functioning (accuracy) and impulsivity but not compulsive
      perseveration. In parallel studies using microdialysis technique and Western blot
      analysis we found that (R)-CPP (100 MUM) infused in the medial prefrontal cortex
      increased glutamate efflux whereas injected in the medial prefrontal cortex at a
      dose causing impairments in attentional performance (50 ng/side) increased p
      S(133)CREB in the frontal cortex (FC), decreased it in the caudate-putamen (CPu)
      and was without effect in the nucleus accumbens (NAC). LY379268 at the dose
      effective in reducing (R)-CPP-induced behavioral deficit reduced both the (R)-CPP
      induced rise in glutamate efflux in the prefrontal cortex and the increase in p
      S(133)CREB in the frontal cortex but was without effect on the decrease in p
      S(133)CREB in the caudate-putamen. The data provide evidence that enhanced
      glutamate release and phosphorylation of cAMP response element binding protein
      (CREB) on serine 133 may be associated to attention deficit and loss of impulse
      control. Furthermore they suggest that mGluR2/3 agonists have a therapeutic
      potential for cognitive deficits.

PMID- 21193021
TI  - Effects of context novelty vs. familiarity on latent inhibition with a
      conditioned taste aversion procedure.
AB  - The latent inhibition phenomenon is observed when a conditioned stimulus is
      preexposed without any consequence before conditioning. The result of this
      manipulation is a reduction in conditioned response intensity to such a stimulus.
      In this study, we analyse the role of context novelty/familiarity on LI
      modulation by changing the context using a three-stage conditioned taste aversion
      procedure. Experiment 1 revealed that, similar to other learning procedures, a
      context change between preexposure and conditioning/testing (but not between
      preexposure/conditioning and testing) resulted in LI attenuation when the
      experimental contexts were novel. Experiment 2, using animals' home cages as one
      of the contexts, revealed a different pattern of results, with an unexpected
      increase in LI magnitude when the context change was introduced between
      conditioning and test stages. The Schmajuk et al. (1996) computational model
      explains these results in terms of the increased novelty of the conditioned
      stimulus during preexposure, conditioning, and testing.

PMID- 21193022
TI  - The limited distribution of Helitrons to vesper bats supports horizontal
      transfer.
AB  - Transposable elements (TEs) have the unique ability to move and replicate within
      the genome and therefore engender dramatic changes to genome architecture. Among
      different types of TEs, rolling-circle transposons (Helitrons) are well known for
      their ability to capture and amplify host gene fragments. Bioinformatic analysis
      revealed that Helitrons constitute ~3% of the Myotis lucifugus, (little brown
      bat) genome, while no Helitrons were found in any of the other 44+ sequenced
      mammalian genomes. Recently horizontal transfer has been implicated for some of
      the M. lucifugus Helitrons, in part explaining this disparate distribution among
      mammals. The purpose of this work is to determine both the distribution of
      Helitrons among bats and to estimate the number of independent invasions. We
      employed a combination of in silico, PCR and hybridization based techniques to
      identify Helitrons from diverse bat species belonging to ten different families.
      This work reveals that Helitrons invaded the vesper bat lineage, at least once.
      Indeed, Helitrons were not identified in the sister taxa 'Miniopterus', which
      suggests that the amplification of Helibat occurred (30-36 mya) only in the
      vesper bat lineage. The estimated age of amplification of the Helibats and the
      rapid radiation of vesper bats are roughly coincidental and suggest that the
      invasion and amplification of these elements might have influenced their
      evolutionary trajectory potentially contributing to phenotypic and genotypic
      diversity.

PMID- 21193018
TI  - Role of Notch and its oncogenic signaling crosstalk in breast cancer.
AB  - The Notch signaling plays a key role in cell differentiation, survival, and
      proliferation through diverse mechanisms. Notch signaling is also involved in
      vasculogenesis and angiogenesis. Moreover, Notch expression is regulated by
      hypoxia and inflammatory cytokines (IL-1, IL-6 and leptin). Entangled crosstalk
      between Notch and other developmental signaling (Hedgehog and Wnt), and signaling
      triggered by growth factors, estrogens and oncogenic kinases, could impact on
      Notch targeted genes. Thus, alterations of the Notch signaling can lead to a
      variety of disorders, including human malignancies. Notch signaling is activated
      by ligand binding, followed by ADAM/tumor necrosis factor-alpha-converting enzyme
      (TACE) metalloprotease and gamma-secretase cleavages that produce the Notch
      intracellular domain (NICD). Translocation of NICD into the nucleus induces the
      transcriptional activation of Notch target genes. The relationships between Notch
      deregulated signaling, cancer stem cells and the carcinogenesis process
      reinforced by Notch crosstalk with many oncogenic signaling pathways suggest that
      Notch signaling may be a critical drug target for breast and other cancers. Since
      current status of knowledge in this field changes quickly, our insight should be
      continuously revised. In this review, we will focus on recent advancements in
      identification of aberrant Notch signaling in breast cancer and the possible
      underlying mechanisms, including potential role of Notch in breast cancer stem
      cells, tumor angiogenesis, as well as its crosstalk with other oncogenic
      signaling pathways in breast cancer. We will also discuss the prognostic value of
      Notch proteins and therapeutic potential of targeting Notch signaling for cancer
      treatment.

PMID- 21193023
TI  - Consensus of local knowledge on medicinal plants among traditional healers in
      Mayiladumparai block of Theni District, Tamil Nadu, India.
AB  - AIM OF THE STUDY: The role of ethnobotany in drug discovery is huge but there are
      criticisms over such studies due to their qualitative nature. The present study
      is aimed at quantitatively abstracting the medicinal plant knowledge of the
      healers trained in traditional ways, in Mayiladumparai block of Theni District,
      Tamil Nadu, India. MATERIALS AND METHODS: The interviews and field observations
      were carried out in all the 18 village panchayaths from January to June 2010,
      consisting of 148 field days. The interviews were conducted with 80 traditional
      healers, after obtaining prior informed consent. Successive free listing was used
      to interview the informants. The informant consensus factor (F(ic)) was
      calculated to estimate the use variability of medicinal plants. Fidelity index
      and Cultural importance index were also calculated to analyze the data. RESULTS:
      This study recorded the ethno-medicinal usage of 142 ethno-species belonging to
      62 families that were used to prepare 504 formulations. Jaundice had the highest
      F(ic) value than all the illness categories studied. Phyllanthus spp. was the
      highly cited medicinal plant to treat jaundice and had high fidelity index value.
      This was followed by Senna angustifolia and Terminalia chebula as laxatives. The
      highly cited medicinal plants in each group with high F(ic) value were Pongamia
      pinnata (antiseptic), Aerva lanata (antidote and snakebite), Blepharis
      maderaspatensis (cuts and wounds), Abutilon indicum (hemorrhoids), Ruta
      graveolens (spiritual medicine), Ocimum tenuiflorum (cough), and Solanum
      trilobatum (pulmonary ailments). Phyllanthus spp., was the most culturally
      significant species according to this index, followed by Borassus flebellifer.
      CONCLUSION: The process of drug discovery has become highly expensive and post
      approval and post-marketing withdrawal of drugs is continuing. In such scenario,
      reverse pharmacology is considered an attractive option. The medicinal plants
      enumerated in this study with high number of citations and high F(ic) values for
      illness categories might give some useful leads for further biomedical research.

PMID- 21193024
TI  - Alcoholism and inflammation: neuroimmunology of behavioral and mood disorders.
AB  - Alcohol abuse changes behavior and can induce major mood disorders such as
      depression. Recent evidence in pre-clinical rodent models and humans now supports
      the conclusion that the innate immune system is an important physiological link
      between alcoholism and major depressive disorders. Deficiency of toll-like
      receptor 4 (TLR4), a protein that has been known to immunologists for 50 years,
      not only prevents lipopolysaccharide (LPS)-induced sickness behavior but recently
      has been demonstrated to induce resistance to chronic alcohol ingestion.
      Activation of the immune system by acute administration of LPS, a TLR4 agonist,
      as well as chronic infection with Bacille Calmette-Guerin (BCG), causes
      development of depressive-like behaviors in pre-clinical rodent models. Induction
      of an enzyme expressed primarily in macrophages and microglia, 2,3 indoleamine
      dioxygenase, shunts tryptophan catabolism to form kynurenine metabolites. This
      enzyme is both necessary and sufficient for expression of LPS and BCG-induced
      depressive-like behaviors in mice. New findings have extended these concepts to
      humans by showing that tryptophan catabolites of 2,3 indoleamine dioxygenase are
      elevated in the cerebrospinal fluid of hepatitis patients treated with the
      recombinant cytokine interferon-alpha. The remarkable conservation from mice to
      humans of the impact of inflammation on mood emphasizes the ever-expanding role
      for cross-talk among diverse physiological symptoms that are likely to be
      involved in the pathogenesis of alcohol abuse. These findings present new and
      challenging opportunities for scientists who are engaged in brain, behavior and
      immunity research.

PMID- 21193025
TI  - CXCR4 signaling mediates morphine-induced tactile hyperalgesia.
AB  - Morphine and related compounds are the first line of therapy in the treatment of
      moderate to severe pain. Over time, individuals taking opioids can develop an
      increasing sensitivity to noxious stimuli, even evolving into a painful response
      to previously non-noxious stimuli (opioid-induced hyperalgesia; OIH). The
      mechanism underlying OIH is not well understood although complex intracellular
      neural mechanisms, including opioid receptor desensitization and down-regulation,
      are believed to be major mechanisms underlying OIH. However, OIH may also be
      associated with changes in gene expression. A growing body of evidence suggests
      that cellular exposure to mu agonists upregulate chemokines/receptors and recent
      work from our laboratory implicates chemokine upregulation in a variety of
      neuropathic pain behaviors. Here we characterized the degree to which
      chemokines/receptors signaling is increased in primary afferent neurons of the
      dorsal root ganglion (DRG) following chronic morphine sulfate treatment and
      correlated these changes with tactile hyperalgesic behavior in rodents. We
      demonstrate that mRNA expression of the chemokine, stromal-derived factor-1
      (SDF1/CXCL12) is upregulated following morphine treatment in sensory neurons of
      the rat. The release of SDF1 was found to be constitutive when compared with the
      activity dependent release of the C-C chemokine, monocyte chemoattractant protein
      1 (MCP1/CCL2) in a line of F11 neuroblastoma-sensory neuron hybrid cells. We
      further determined that there is pronounced CXCR4 expression in satellite glial
      cells and following morphine treatment, increased functional CXCR4 expression in
      sensory neurons of the DRG. Moreover, intraperitoneal administration of the
      specific CXCR4 antagonist, AMD3100, completely reversed OIH in the rat. Taken
      together; the data suggest that opioid-induced SDF1/CXCR4 signaling is central to
      the development of long lasting OIH and that receptor antagonists represent a
      promising novel approach to the management of the side effects associated with
      the use of opioids for chronic pain management.

PMID- 21193026
TI  - Advances in the identification of Malassezia.
AB  - Members of the genus Malassezia are lypophilic and/or lipid-dependent, unipolar
      budding yeasts that can become pathogenic under the influence of particular
      predisposing factors (e.g., changes in the cutaneous microenvironment and/or
      alterations in host defences). This genus comprises at least 14 species, which
      have been identified traditionally based on their morphology and biochemical
      features. However, phenetic characteristics often do not allow the identification
      or delineation of closely related Malassezia spp., such that molecular tools need
      to be used to assist in fundamental studies of the epidemiology and ecology of
      Malassezia as well as aspects of the pathogenesis and disease caused by members
      of this genus. This article briefly reviews the morphological and biochemical
      methods commonly used for the identification of Malassezia as well as DNA
      technological methods that have been established for the specific identification
      of members of this genus and the diagnosis of their infections. New avenues for
      the development of improved molecular-diagnostic methods to overcome diagnostic
      limitations and to underpin fundamental investigations of this interesting group
      of yeasts are proposed.

PMID- 21193027
TI  - Effect of template on generating a standard curve for absolute quantification of
      an RNA virus by real-time reverse transcriptase-polymerase chain reaction.
AB  - The effect of different templates on generating standard curves that are needed
      for the absolute quantification of an RNA virus by real-time reverse
      transcriptase-PCR (RT-PCR) was evaluated. We used infectious pancreatic necrosis
      virus (IPNV), a major viral pathogen of wild and cultured salmon, as a RNA virus
      example for the study. A dilution series of four different templates representing
      the IPNV protease gene (two in vitro transcribed RNAs of 100 bases and 500 bases
      in length, a plasmid DNA and a DNA oligo) were used as template to produce
      standard curves to quantify IPNV load in rainbow trout. The slope, the goodness
      of fit (r(2)), and the efficiency (e) of PCR were statistically equivalent
      irrespective of the nature of template used in the PCR. Using a factorial ANOVA,
      no significant difference in IPNV copy number was observed using the four
      different standard curves for absolute quantification of IPNV in experimentally
      challenged rainbow trout. However, when IPNV transcript abundance was less than
      100 copies per reaction and when the template size was bigger than the amplicon
      size amplification was more variable. The data suggests that the size of the
      template used to generate standard curve should be very similar to the size of
      the amplicon. A synthetic DNA oligo template would be optimal for this purpose as
      it can be custom made and only requires the sequence information for its
      synthesis. However, if the standard curve is generated with template copy number
      in excess of 100 copies per reaction, the nature of the template has no effect on
      the standard curve, and therefore, the cheaper template would be the preferred
      choice of template over the other more expensive options.

PMID- 21193028
TI  - Dopamine D1 receptor-mediated inhibition of NADPH oxidase activity in human
      kidney cells occurs via protein kinase A-protein kinase C cross talk.
AB  - Dopamine cellular signaling via the D(1) receptor (D(1)R) involves both protein
      kinase A (PKA) and protein kinase C (PKC), but the PKC isoform involved has not
      been determined. Therefore, we tested the hypothesis that the D(1)R-mediated
      inhibition of NADPH oxidase activity involves cross talk between PKA and a
      specific PKC isoform(s). In HEK-293 cells heterologously expressing human D(1)R
      (HEK-hD(1)), fenoldopam, a D(1)R agonist, and phorbol 12-myristate 13-acetate
      (PMA), a PKC activator, inhibited oxidase activity in a time- and concentration
      dependent manner. The D(1)R-mediated inhibition of oxidase activity (68.1+/-3.6%)
      was attenuated by two PKA inhibitors, H89 (10MUmol/L; 88+/-8.1%) and Rp-cAMP
      (10MUmol/L; 97.7+/-6.7%), and two PKC inhibitors, bisindolylmaleimide I
      (1MUmol/L; 94+/-6%) and staurosporine (10nmol/L; 93+/-8%), which by themselves
      had no effect (n=4-8/group). The inhibitory effect of PMA (1MUmol/L) on oxidase
      activity (73+/-3.2%) was blocked by H89 (100+/-7.8%; n=5 or 6/group). The PMA
      mediated inhibition of NADPH oxidase activity was accompanied by an increase in
      PKCtheta(S676), an effect that was also blocked by H89. Fenoldopam (1MUmol/L)
      also increased PKCtheta(S676) in HEK-hD(1) and human renal proximal tubule (RPT)
      cells. Knockdown of PKCtheta with siRNA in RPT cells prevented the inhibitory
      effect of fenoldopam on NADPH oxidase activity. Our studies demonstrate for the
      first time that cross talk between PKA and PKCtheta plays an important role in
      the D(1)R-mediated negative regulation of NADPH oxidase activity in human kidney
      cells.

PMID- 21193029
TI  - A global transcriptomic view of the multifaceted role of glutathione peroxidase-1
      in cerebral ischemic-reperfusion injury.
AB  - Transient cerebral ischemia often results in secondary ischemic/reperfusion
      injury, the pathogenesis of which remains unclear. This study provides a
      comprehensive, temporal description of the molecular events contributing to
      neuronal injury after transient cerebral ischemia. Intraluminal middle cerebral
      artery occlusion (MCAO) was performed to induce a 2-h ischemia with reperfusion.
      Microarray analysis was then performed on the infarct cortex of wild-type (WT)
      and glutathione peroxidase-1 (a major antioxidant enzyme) knockout (Gpx1(-/-))
      mice at 8 and 24h postreperfusion to identify differential gene expression
      profile patterns and potential alternative injury cascades in the absence of
      Gpx1, a crucial antioxidant enzyme, in cerebral ischemia. Genes with at least +/
      1.5-fold change in expression at either time point were considered significant.
      Global transcriptomic analyses demonstrated that 70% of the WT-MCAO profile
      overlapped with that of Gpx1(-/-)-MCAO, and 28% vice versa. Critical analysis of
      the 1034 gene probes specific to the Gpx1(-/-)-MCAO profile revealed regulation
      of additional novel pathways, including the p53-mediated proapoptotic pathway and
      Fas ligand (CD95/Apo1)-mediated pathways; downplay of the Nrf2 antioxidative
      cascade; and ubiquitin-proteasome system dysfunction. Therefore, this comparative
      study forms the foundation for the establishment of screening platforms for
      target definition in acute cerebral ischemia intervention.

PMID- 21193030
TI  - Highly active antiretroviral therapy drug combination induces oxidative stress
      and mitochondrial dysfunction in immortalized human blood-brain barrier
      endothelial cells.
AB  - The era of highly active antiretroviral therapy (HAART) has controlled AIDS and
      its related disorders considerably; however, the prevalence of HIV-1-associated
      neurocognitive disorders has been on the rise in the post-HAART era. In view of
      these developments, we investigated whether a HAART drug combination of 3'-azido
      2',3'-deoxythymidine (AZT) and indinavir (IDV) can alter the functionality of the
      blood-brain barrier (BBB) endothelial cells, thereby exacerbating this condition.
      The viability of hCMEC/D3 cells (in vitro model of BBB) that were exposed to
      these drugs was significantly reduced after 72h treatment, in a dose-dependent
      manner. Reactive oxygen species were highly elevated after the exposure,
      indicating that mechanisms that induce oxidative stress were involved. Measures
      of oxidative stress parameters, such as glutathione and malondialdehyde, were
      altered in the treated groups. Loss of mitochondrial membrane potential, as
      assessed by fluorescence microscopy and decreased levels of ATP, indicated that
      cytotoxicity was mediated through mitochondrial dysfunction. Furthermore, AZT+IDV
      treatment caused apoptosis in endothelial cells, as assessed by the expression of
      cytochrome c and procaspase-3 proteins. Pretreatment with the thiol antioxidant N
      acetylcysteine amide reversed some of the pro-oxidant effects of AZT+IDV. Results
      from our in vitro studies indicate that the AZT+IDV combination may affect the
      BBB in HIV-infected individuals treated with HAART drugs.

PMID- 21193031
TI  - Effects of iron deficiency and iron overload on angiogenesis and oxidative stress
      a potential dual role for iron in breast cancer.
AB  - Estrogen alone cannot explain the differences in breast cancer (BC) recurrence
      and incidence rates in pre- and postmenopausal women. In this study, we have
      tested a hypothesis that, in addition to estrogen, both iron deficiency due to
      menstruation and iron accumulation as a result of menstrual stop play important
      roles in menopause-related BC outcomes. We first tested this hypothesis in cell
      culture models mimicking the high-estrogen and low-iron premenopausal condition
      or the low-estrogen and high-iron postmenopausal condition. Subsequently, we
      examined this hypothesis in mice that were fed iron-deficient and iron-overloaded
      diets. We show that estrogen only slightly up-regulates vascular endothelial
      growth factor (VEGF), an angiogenic factor known to be important in BC
      recurrence. It is, rather, iron deficiency that significantly promotes VEGF by
      stabilizing hypoxia-inducible factor-1alpha. Conversely, high iron levels
      increase oxidative stress and sustain mitogen-activated protein kinase
      activation, which are mechanisms of known significance in BC development. Taken
      together, our results suggest, for the first time, that an iron-deficiency
      mediated proangiogenic environment could contribute to the high recurrence of BC
      in young patients, and iron-accumulation-associated pro-oxidant conditions could
      lead to the high incidence of BC in older women.

PMID- 21193032
TI  - Molecular basis for gene-specific transactivation by nuclear receptors.
AB  - Nuclear receptors (NRs) are key transcriptional regulators of metazoan physiology
      and metabolism. Different NRs bind to similar or even identical core response
      elements; however, they regulate transcription in a highly receptor- and gene
      specific manner. These differences in gene activation can most likely be
      accounted for by mechanisms involving receptor-specific interactions with DNA as
      well as receptor-specific interactions with protein complexes binding to adjacent
      and distant DNA sequences. Here, we review key molecular aspects of
      transactivation by NRs with special emphasis on the recent advances in the
      molecular mechanisms responsible for receptor- and gene-specific transcriptional
      activation. This article is part of a Special Issue entitled: Translating nuclear
      receptors from health to disease.

PMID- 21193033
TI  - Liver X receptors as regulators of macrophage inflammatory and metabolic
      pathways.
AB  - The liver X receptors (LXRalpha and LXRbeta) are members of the nuclear receptor
      family of transcription factors that play essential roles in the transcriptional
      control of lipid metabolism. LXRs are endogenously activated by modified forms of
      cholesterol known as oxysterols and control the expression of genes important for
      cholesterol uptake, efflux, transport, and excretion in multiple tissues. In
      addition to their role as cholesterol sensors, a number of studies have
      implicated LXRs in the modulation of innate and adaptive immune responses. Both
      through activation and repression mechanisms, LXRs regulate diverse aspects of
      inflammatory gene expression in macrophages. The ability of LXRs to coordinate
      metabolic and immune responses constitutes an attractive therapeutic target for
      the treatment of chronic inflammatory disorders. This article is part of a
      Special Issue entitled: Translating nuclear receptors from health to disease.

PMID- 21193035
TI  - Mast cell activation and autism.
AB  - Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by
      varying degrees of dysfunctional communication and social interactions,
      repetitive and stereotypic behaviors, as well as learning and sensory deficits.
      Despite the impressive rise in the prevalence of autism during the last two
      decades, there are few if any clues for its pathogenesis, early detection or
      treatment. Increasing evidence indicates high brain expression of pro
      inflammatory cytokines and the presence of circulating antibodies against brain
      proteins. A number of papers, mostly based on parental reporting on their
      children's health problems, suggest that ASD children may present with "allergic
      like" problems in the absence of elevated serum IgE and chronic urticaria. These
      findings suggest non-allergic mast cell activation, probably in response to
      environmental and stress triggers that could contribute to inflammation. In utero
      inflammation can lead to preterm labor and has itself been strongly associated
      with adverse neurodevelopmental outcomes. Premature babies have about four times
      higher risk of developing ASD and are also more vulnerable to infections, while
      delayed development of their gut-blood-brain barriers makes exposure to potential
      neurotoxins likely. Perinatal mast cell activation by infectious, stress-related,
      environmental or allergic triggers can lead to release of pro-inflammatory and
      neurotoxic molecules, thus contributing to brain inflammation and ASD
      pathogenesis, at least in a subgroup of ASD patients. This article is part of a
      Special Issue entitled: Mast cells in inflammation.

PMID- 21193036
TI  - The development of a whole-cell based medium throughput screening system for the
      discovery of human aldosterone synthase (CYP11B2) inhibitors: old drugs disclose
      new applications for the therapy of congestive heart failure, myocardial fibrosis
      and hypertension.
AB  - Cytochrome P450 enzymes play an important role in steroid hormone biosynthesis of
      the human adrenal gland, e.g., the production of cortisol and aldosterone.
      Aldosterone, the most important human mineralocorticoid, is involved in the
      regulation of the salt and water homeostasis of the body and thus in the
      regulation of blood pressure, whereas cortisol is the most important
      glucocorticoid of the human body. CYP11B-dependent steroid hydroxylases are drug
      development targets, and since they are very closely related enzymes, the
      discovery of selective inhibitors has been subject to intense investigations for
      several years. Here we report the development of a whole-cell medium throughput
      screening technology for the discovery of CYP11B2 inhibitors. The new screening
      system displayed high reproducibility and was applied to investigate a library of
      pharmacologically active compounds. 1268 compounds were investigated during this
      study which revealed 5 selective inhibitors of CYP11B2 (after validation against
      CYP11B1). The new inhibitors of CYP11B2 are already existing drugs that could be
      used either in the treatment of hyperaldosteronism-related diseases or as lead
      compounds that could further be optimised to achieve safer and selective
      inhibitors of aldosterone synthase. Article from the Special issue on 'Targeted
      Inhibitors'.

PMID- 21193034
TI  - Role of nuclear receptor corepressor RIP140 in metabolic syndrome.
AB  - Obesity and its associated complications, which can lead to the development of
      metabolic syndrome, are a worldwide major public health concern especially in
      developed countries where they have a very high prevalence. RIP140 is a nuclear
      coregulator with a pivotal role in controlling lipid and glucose metabolism.
      Genetically manipulated mice devoid of RIP140 are lean with increased oxygen
      consumption and are resistant to high-fat diet-induced obesity and hepatic
      steatosis with improved insulin sensitivity. Moreover, white adipocytes with
      targeted disruption of RIP140 express genes characteristic of brown fat including
      CIDEA and UCP1 while skeletal muscles show a shift in fibre type composition
      enriched in more oxidative fibres. Thus, RIP140 is a potential therapeutic target
      in metabolic disorders. In this article we will review the role of RIP140 in
      tissues relevant to the appearance and progression of the metabolic syndrome and
      discuss how the manipulation of RIP140 levels or activity might represent a
      therapeutic approach to combat obesity and associated metabolic disorders. This
      article is part of a Special Issue entitled: Translating nuclear receptors from
      health to disease.

PMID- 21193037
TI  - Assisted reproduction technologies alter steroid delivery to the mouse fetus
      during pregnancy.
AB  - Assisted reproduction technologies (ART) include in vitro fertilization (IVF) and
      intracytoplasmic sperm injection (ICSI), and are common treatments for
      infertility. Although generally successful, ART warrant further investigations
      due to emerging perinatal issues, especially low birth weight. Herein we extend
      our previous work demonstrating higher steroid clearance in murine ART placentas
      by examining steroid biosynthesis and the directional flow of steroids in the
      maternal-placental-fetal units. The activities of the major steroidogenic enzymes
      3beta-hydroxysteroid dehydrogenase (3beta-HSD) and cytochrome P450 17
      alphahydroxylase (CYP17) were assessed in maternal liver and ovaries and fetal
      livers as were levels of cholesterol, progesterone, estrone (E1), and estradiol
      (E2) in the maternal, placental and fetal units. No structural abnormalities were
      found in placentas from ART. Although ART increased 3beta-HSD activity in
      maternal livers, there were no other changes in 3beta-HSD- or CYP17-mediated
      steroidogenesis. Cholesterol levels were significantly lower in maternal livers
      of ICSI pregnancies and in placentas from both IVF and ICSI pregnancies but not
      altered in the fetal livers. Progesterone levels were higher in maternal and
      fetal livers in IVF and ICSI, respectively, but were significantly lowered in
      ICSI placentas, compared to normal fertilization. For estrogenic hormones, no
      differences in E1 or E2 levels were observed in maternal livers but ICSI
      significantly increased both E1 and E2 levels in placentas while both IVF and
      ICSI significantly lowered E1 but raised E2 levels in fetal livers. In summary,
      while steroid production was normal, steroid diffusion/flow from mother to fetus
      was altered in murine pregnancies conceived by ART. This appears to occur, at
      least in part; through placental mechanisms. Impaired cholesterol and steroid
      transfer may affect correct regulation of fetal growth and development.

PMID- 21193038
TI  - Associations between polymorphisms in glucuronidation and sulfation enzymes and
      sex steroid concentrations in premenopausal women in the United States.
AB  - Glucuronidation, catalyzed by UDP-glucuronosyltransferases (UGT) and sulfation,
      catalyzed by sulfotransferases (SULT), are pathways through which sex steroids
      are metabolized to less active compounds. These enzymes are highly polymorphic
      and genetic variants frequently result in higher or lower activity. The
      phenotypic effects of these polymorphisms on circulating sex steroids in
      premenopausal women have not yet been investigated. One hundred and seventy women
      aged 40-45 years had a blood sample drawn during the follicular phase of the
      menstrual cycle for sex steroid measures and to obtain genomic DNA. Urine was
      collected for 2-hydroxy (OH) estrone (E(1)) and 16alpha-OH E(1) measures.
      Generalized linear regression models were used to assess associations between sex
      steroids and polymorphisms in the UGT1A and UGT2B families, SULT1A1, and SULT1E1.
      Women with the UGT1A1(TA7/TA7) genotype had 25% lower mean estradiol (E(2))
      concentrations compared to the wildtype (TA6/TA6) (p=0.02). Similar associations
      were observed between SULT1A1(R213/H213) and E(1) (13% lower mean E(1)
      concentration vs. wildtype; p-value=0.02) and UGT2B4(E458/E458) and
      dehydroepiandrosterone (DHEA) (20% lower mean DHEA vs. wildtype; p-value=0.03).
      The SULT1E1(A/C) and the UGT1A1(TA7)-UGT1A3(R11) haplotypes were associated with
      reduced estrogen concentrations. Further study of UGT and SULT polymorphisms and
      circulating sex steroid measures in larger populations of premenopausal women is
      warranted.

PMID- 21193039
TI  - 17beta-Hydroxysteroid dehydrogenases (17beta-HSDs) as therapeutic targets:
      protein structures, functions, and recent progress in inhibitor development.
AB  - 17beta-Hydroxysteroid dehydrogenases (17beta-HSDs) are oxidoreductases, which
      play a key role in estrogen and androgen steroid metabolism by catalyzing final
      steps of the steroid biosynthesis. Up to now, 14 different subtypes have been
      identified in mammals, which catalyze NAD(P)H or NAD(P)(+) dependent
      reductions/oxidations at the 17-position of the steroid. Depending on their
      reductive or oxidative activities, they modulate the intracellular concentration
      of inactive and active steroids. As the genomic mechanism of steroid action
      involves binding to a steroid nuclear receptor, 17beta-HSDs act like pre-receptor
      molecular switches. 17beta-HSDs are thus key enzymes implicated in the different
      functions of the reproductive tissues in both males and females. The crucial role
      of estrogens and androgens in the genesis and development of hormone dependent
      diseases is well recognized. Considering the pivotal role of 17beta-HSDs in
      steroid hormone modulation and their substrate specificity, these proteins are
      promising therapeutic targets for diseases like breast cancer, endometriosis,
      osteoporosis, and prostate cancer. The selective inhibition of the concerned
      enzymes might provide an effective treatment and a good alternative to the
      existing endocrine therapies. Herein, we give an overview of functional and
      structural aspects for the different 17beta-HSDs. We focus on steroidal and non
      steroidal inhibitors recently published for each subtype and report on existing
      animal models for the different 17beta-HSDs and the respective diseases. Article
      from the Special issue on Targeted Inhibitors.

PMID- 21193041
TI  - Olprinone, a specific phosphodiesterase (PDE)-III inhibitor, reduces the
      development of multiple organ dysfunction syndrome in mice.
AB  - Olprinone is a specific phosphodiesterase (PDE)-III inhibitor, which has been
      found to have anti-inflammatory effects in addition to its main inotropic and
      peripheral vasodilatory effects. In the present study we investigated the effects
      of olprinone (0.2mg/kg, i.p.) on the development of zymosan-induced multiple
      organ failure in mice. Treatment with olprinone attenuated the peritoneal
      exudation and the migration of polymorphonuclear cells caused by zymosan.
      Olprinone also attenuated the lung, liver and pancreatic injury, renal
      dysfunction as well as the increased lung and intestine myeloperoxidase (MPO)
      activity caused by zymosan. Immunohistochemical analysis for inducible nitric
      oxide synthase (iNOS), nitrotyrosine, poly(ADP-ribose) (PAR), tumor necrosis
      factor-alpha (TNF-alpha) and interleuchin-1beta (IL-1beta) revealed positive
      staining in pancreatic and intestinal tissue obtained from zymosan-injected mice.
      The degree of staining for nitrotyrosine, iNOS, PAR, TNF-alpha and IL-1beta was
      markedly reduced in tissue sections obtained from zymosan-injected mice, which
      had received olprinone. In addition, administration of zymosan caused a severe
      illness in the mice characterized by significant loss of body weight and a 60% of
      mortality at the end of observation period (7 days). Treatment with olprinone
      significantly reduced the development of systemic toxicity, loss in body weight
      and mortality, caused by zymosan. This study provides evidence that olprinone
      attenuates the degree of zymosan-induced shock in mice.

PMID- 21193040
TI  - Weight control and prevention of metabolic syndrome by green tea.
AB  - Green tea (Camellia sinensis, Theaceace) is the second most popular beverage in
      the world and has been extensively studied for its putative disease preventive
      effects. Green tea is characterized by the presence of a high concentrations of
      polyphenolic compounds known as catechins, with (-)-epigallocatechin-3-gallate
      (EGCG) being the most abundant and most well-studied. Metabolic syndrome (MetS)
      is a complex condition that is defined by the presence of elevated waist
      circumference, dysglycemia, elevated blood pressure, decrease serum high-density
      lipoprotein-associated cholesterol, and increased serum triglycerides. Studies in
      both in vitro and laboratory animal models have examined the preventive effects
      of green tea and EGCG against the symptoms of MetS. Overall, the results of these
      studies have been promising and demonstrate that green tea and EGCG have
      preventive effects in both genetic and dietary models of obesity, insulin
      resistance, hypertension, and hypercholesterolemia. Various mechanisms have been
      proposed based on these studies and include: modulation of dietary fat absorption
      and metabolism, increased glucose utilization, decreased de novo lipogenesis,
      enhanced vascular responsiveness, and antioxidative effects. In the present
      review, we discuss the current state of the science with regard to laboratory
      studies on green tea and MetS. We attempt to critically evaluate the available
      data and point out areas for future research. Although there is a considerable
      amount of data available, questions remain in terms of the primary mechanism(s)
      of action, the dose-response relationships involved, and the best way to
      translate the results to human intervention studies.

PMID- 21193042
TI  - Fish oil decreases inflammation and reduces cardiac remodeling in rosiglitazone
      treated aging mice.
AB  - Clinical studies suggest that rosiglitazone (RSG) treatment may increase the
      incidence of heart failure in diabetic patients. In this study, we examined
      whether a high corn oil diet with RSG treatment in insulin resistant aging mice
      exerted metabolic and pro-inflammatory effects that stimulate cardiac
      dysfunction. We also evaluated whether fish oil attenuated these effects. Female
      C57BL/6J mice (13 months old) were divided into 5 groups: (1) lean control (LC),
      (2) corn oil, (3) fish oil, (4) corn oil+RSG and (5) fish oil+RSG. Mice fed a
      corn oil enriched diet and RSG developed hypertrophy of the left ventricle (LV)
      and decreased fractional shortening, despite a significant increase in total body
      lean mass. In contrast, LV hypertrophy was prevented in RSG treated mice fed a
      fish oil enriched diet. Importantly, hyperglycemia was controlled in both RSG
      groups. Further, fish oil+RSG decreased LV expression of atrial and brain
      natriuretic peptides, fibronectin and the pro-inflammatory cytokines interleukin
      6 and tumor necrosis factor-alpha, concomitant with increased interleukin-10 and
      adiponectin levels compared to the corn oil+RSG group. Fish oil+RSG treatment
      suppressed inflammation, increased serum adiponectin, and improved fractional
      shortening, attenuating the cardiac remodeling seen in the corn oil+RSG diet fed
      C57BL/6J insulin resistant aging mice. Our results suggest that RSG treatment has
      context-dependent effects on cardiac remodeling and serves a negative cardiac
      role when given with a corn oil enriched diet.

PMID- 21193044
TI  - Endothelin receptor antagonists: potential in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is believed to be initiated by the accumulation of
      neurotoxic forms of Abeta peptide within the brain. AD patients show reduction of
      cerebral blood flow (CBF), the extent of the reduction correlating with the
      impairment of cognition. There is evidence that cerebral hypoperfusion precedes
      and may even trigger the onset of dementia in AD. Cerebral hypoperfusion impairs
      neuronal function, reduces the clearance of Abeta peptide and other toxic
      metabolites from the brain, and upregulates Abeta production. Studies in animal
      models of AD have shown the reduction in CBF to be more than would be expected
      for the reduction in neuronal metabolic activity. Abeta may contribute to the
      reduction in CBF in AD, as both Abeta1-40 and Abeta1-42 induce cerebrovascular
      dysfunction. Abeta1-40 acts directly on cerebral arteries to cause cerebral
      smooth muscle cell contraction. Abeta1-42 causes increased neuronal production
      and release of endothelin-1 (ET-1), a potent vasoconstrictor, and upregulation of
      endothelin-converting enzyme-2 (ECE-2), the enzyme which cleaves ET-1 from its
      inactive precursor. ET-1 and ECE-2 are also elevated in AD, making it likely that
      upregulation of the ECE-2-ET-1 axis by Abeta1-42 contributes to the chronic
      reduction of CBF in AD. At present, only a few symptomatic treatment options
      exist for AD. The involvement of ET-1 in the pathogenesis of endothelial
      dysfunction associated with elevated Abeta indicates the potential for endothelin
      receptor antagonists in the treatment of AD. It has already been demonstrated
      that the endothelin receptor antagonist bosentan, preserves aortic and carotid
      endothelial function in Tg2576 mice, and our findings suggest that endothelin
      receptor antagonists may be beneficial in maintaining CBF in AD.

PMID- 21193043
TI  - Long-term high-dose atorvastatin decreases brain oxidative and nitrosative stress
      in a preclinical model of Alzheimer disease: a novel mechanism of action.
AB  - Alzheimer disease (AD) is an age-related neurodegenerative disorder characterized
      by progressive memory loss, inability to perform the activities of daily living
      and personality changes. Unfortunately, drugs effective for this disease are
      limited to acetylcholinesterase inhibitors that do not impact disease
      pathogenesis. Statins, which belong to the class of cholesterol-reducing drugs,
      were proposed as novel agents useful in AD therapy, but the mechanism underlying
      their neuroprotective effect is still unknown. In this study, we show that
      atorvastatin may have antioxidant effects, in aged beagles, that represent a
      natural higher mammalian model of AD. Atorvastatin (80 mg/day for 14.5 months)
      significantly reduced lipoperoxidation, protein oxidation and nitration, and
      increased GSH levels in parietal cortex of aged beagles. This effect was specific
      for brain because it was not paralleled by a concomitant reduction in all these
      parameters in serum. In addition, atorvastatin slightly reduced the formation of
      cholesterol oxidation products in cortex but increased the 7
      ketocholesterol/total cholesterol ratio in serum. We also found that increased
      oxidative damage in the parietal cortex was associated with poorer learning
      (visual discrimination task). Thus, a novel pharmacological effect of
      atorvastatin mediated by reducing oxidative damage may be one mechanism
      underlying benefits of this drug in AD.

PMID- 21193045
TI  - The intestinal anti-inflammatory effect of minocycline in experimental colitis
      involves both its immunomodulatory and antimicrobial properties.
AB  - Some antibiotics, including minocycline, have recently been reported to display
      immunomodulatory properties in addition to their antimicrobial activity. The use
      of a compound with both immunomodulatory and antibacterial properties could be
      very interesting in the treatment of inflammatory bowel disease (IBD), so the aim
      of our study was to evaluate the anti-inflammatory effect of minocycline in
      several experimental models of IBD. Firstly, the immunomodulatory activity of the
      antibiotic was tested in vitro using Caco-2 intestinal epithelial cells and RAW
      264.7 macrophages; minocycline was able to inhibit IL-8 and nitrite production,
      respectively. In vivo studies were performed in trinitrobenzenesulfonic acid
      (TNBS)-induced rat colitis and dextran sodium sulfate (DSS)-induced mouse
      colitis. The results revealed that minocycline exerted an intestinal anti
      inflammatory effect when administered as a curative treatment in the TNBS model,
      modulating both immune and microbiological parameters, being confirmed in the DSS
      model; whereas none of the other antibiotics tested (tetracycline and
      metronidazole) showed anti-inflammatory effect. However, minocycline
      administration before the colitis induction was not able to prevent the
      development of the intestinal inflammation, thus showing that only its
      antimicrobial activity is not enough for the anti-inflammatory effect. In
      conclusion, minocycline displays an anti-inflammatory effect on different models
      of rodent colitis which could be attributed to the association of its
      antibacterial and immunomodulatory properties.

PMID- 21193046
TI  - A pilot trial of the microtubule-interacting peptide (NAP) in mice overexpressing
      alpha-synuclein shows improvement in motor function and reduction of alpha
      synuclein inclusions.
AB  - Abnormal accumulation of alpha-synuclein is associated with several
      neurodegenerative disorders (synucleinopathies), including sporadic Parkinson's
      disease (PD). Genetic mutations and multiplication of alpha-synuclein cause
      familial forms of PD and polymorphisms in the alpha-synuclein gene are associated
      with PD risk. Overexpression of alpha-synuclein can impair essential functions
      within the cell such as microtubule-dependent transport, suggesting that
      compounds that act on the microtubule system may have therapeutic benefit for
      synucleinopathies. In this study, mice overexpressing human wildtype alpha
      synuclein under the Thy1 promoter (Thy1-aSyn) and littermate wildtype control
      mice were administered daily the microtubule-interacting peptide NAPVSIPQ (NAP;
      also known as davunetide or AL-108) intranasally for 2 months starting at 1 month
      of age, in a regimen known to produce effective concentrations of the peptide in
      mouse brain. Motor performance, coordination, and activity were assessed at the
      end of treatment. Olfactory function, which is altered in PD, was measured 1
      month later. Mice were sacrificed at 4.5 months of age, and their brains examined
      for proteinase K-resistant alpha-synuclein inclusions in the substantia nigra and
      olfactory bulb. NAP-treated Thy1-aSyn mice showed a 38% decrease in the number of
      errors per step in the challenging beam traversal test and a reduction in
      proteinase K-resistant alpha-synuclein inclusions in the substantia nigra
      compared to vehicle treated transgenics. The data indicate a significant
      behavioral benefit and a long lasting improvement of alpha-synuclein pathology
      following administration of a short term (2 months) NAP administration in a mouse
      model of synucleinopathy.

PMID- 21193048
TI  - Expression and purification of human FROUNT, a common cytosolic regulator of CCR2
      and CCR5.
AB  - Chemokine receptors play pivotal roles for immune cell recruitment to
      inflammation sites, in response to chemokine gradients (chemotaxis). The
      mechanisms of chemokine signaling, especially the initiation of the intracellular
      signaling cascade, are not well understood. We previously identified a
      cytoplasmic protein FROUNT, which binds to the C-terminal regions of CCR2 and
      CCR5 to mediate chemokine signaling. Although large amounts of purified protein
      are required for detailed biochemical studies and drug screening, no method to
      produce recombinant FROUNT has been reported. In this study, we developed a
      method for the production of recombinant human FROUNT. Human FROUNT was
      successfully expressed in Escherichia coli, as a soluble protein fused to the
      folding chaperone Trigger Factor, with a cold shock expression system. The
      purified FROUNT protein displayed CCR2 binding ability without any additional
      components, as demonstrated by SPR measurements. A gel filtration analysis
      suggested that FROUNT exists in a homo-oligomeric state. This high-yield method
      is cost-effective for human FROUNT production. It should be a powerful tool for
      further biochemical and structural studies to elucidate GPCR regulation and
      chemokine signaling, and also will contribute to drug development.

PMID- 21193047
TI  - Sleeping Beauty transposon mutagenesis of the rat genome in spermatogonial stem
      cells.
AB  - Since several aspects of physiology in rats have evolved to be more similar to
      humans than that of mice, it is highly desirable to link the rat into the process
      of annotating the human genome with function. However, the lack of technology for
      generating defined mutants in the rat genome has hindered the identification of
      causative relationships between genes and disease phenotypes. As an important
      step towards this goal, an approach of establishing transposon-mediated
      insertional mutagenesis in rat spermatogonial stem cells was recently developed.
      Transposons can be viewed as natural DNA transfer vehicles that, similar to
      integrating viruses, are capable of efficient genomic insertion. The mobility of
      transposons can be controlled by conditionally providing the transposase
      component of the transposition reaction. Thus, a DNA of interest such as a
      mutagenic gene trap cassette cloned between the inverted repeat sequences of a
      transposon-based vector can be utilized for stable genomic insertion in a
      regulated and highly efficient manner. Gene-trap transposons integrate into the
      genome in a random fashion, and those mutagenic insertions that occurred in
      expressed genes can be selected in vitro based on activation of a reporter.
      Selected monoclonal as well as polyclonal libraries of gene trap clones are
      transplanted into the testes of recipient/founder male rats allowing passage of
      the mutation through the germline to F1 progeny after only a single cross with
      wild-type females. This paradigm enables a powerful methodological pipeline for
      forward genetic screens for functional gene annotation in the rat, as well as
      other vertebrate models. This article provides a detailed description on how to
      culture rat spermatogonial stem cell lines, their transfection with transposon
      plasmids, selection of gene-trap insertions with antibiotics, transplantation of
      genetically modified stem cells and genotyping of knockout animals.

PMID- 21193049
TI  - Expression of the HSV-1 capsid protein VP19C in Escherichia coli: a single amino
      acid change overcomes an expression block of the full-length polypeptide.
AB  - The herpesvirus triplex is a key structural feature of the capsids of these
      viruses. It is composed of a hetero-trimer of one molecule of VP19C and two
      molecules of VP23. It acts to stabilize capsid shells by connecting the
      capsomeric subunits together. Although it has been possible to over-express in
      Escherichia coli and purify one component of the triplex, VP23; this has not been
      the case with VP19C. Because an N-terminal polypeptide of VP19C could be
      expressed and purified using a GST affinity tag, a directed mutagenic approach
      was used to determine the region of VP19C that caused the block in expression of
      the full-length protein. The region was mapped to reside between VP19C amino
      acids 145 and 150 using truncation gene fusions and subsequently a single amino
      acid, R146 was identified which when changed to alanine, allowed stable
      expression and accumulation of VP19C. This change does not affect the biological
      function of VP19C. Finally using this altered VP19C, co-expression of the triplex
      proteins in the same cell has been achieved making it now possible to purify this
      complex for biophysical and structural studies.

PMID- 21193051
TI  - RETRACTED: Molecular characterization and expression analysis of lily type lectin
      1 (OfLTL-1) in rock bream (Oplegnathus fasciatus).
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- 21193050
TI  - Molecular cloning and expression of orange-spotted grouper (Epinephelus coioides)
      CD8alpha and CD8beta genes.
AB  - T-cell surface glycoprotein CD8 consists of two distinguished chains, termed
      alpha and beta chains, and functions as a co-receptor for the T-cell receptor by
      binding to MHC class I proteins. In this study we report the cloning and
      identification of both CD8alpha and CD8beta genes from orange-spotted grouper
      (Epinephelus coioides). The predicted grouper CD8alpha and CD8beta proteins were
      structurally similar to other fish especially to those of Pleuronectiformes. Real
      time RT-PCR revealed that the CD8 mRNA was much higher in the thymus than in
      other immune organs, and the expression level were very low in stomach, liver,
      and brain. During embryonic development of the grouper, the highest CD8
      transcripts were detected in the multi-cell stage, followed by muscle burl stage,
      which suggested that the multi-cell stage may be critical in CD8 transcript
      synthesis. Moreover, CD8 mRNA levels were examined in lymphocytes at different
      time treated with lipopolysaccharide (LPS), polyriboinosinic polyribocytidylic
      acid (PolyI:C), phytohemagglutinin (PHA), and concanavalin A (ConA). The result
      showed that the CD8 mRNA levels were significantly affected in time-dependent
      manner by PolyI:C, PHA, and ConA, but not by LPS.

PMID- 21193052
TI  - Long-term aversive taste memory requires insular and amygdala protein
      degradation.
AB  - Some reports have shown that the ubiquitin-proteasome system (UPS) is necessary
      to degrade repressor factors to produce new proteins essential to memory
      consolidation. Furthermore, recent evidence suggests that memory updating also
      relies on protein degradation through the UPS. To evaluate whether degradation of
      proteins is part of the cellular events needed for long-term storage of taste
      aversion, we injected lactacystin--an UPS inhibitor--into the amygdala and/or
      insular cortex 30 min before the first or second training trials. The results
      revealed that degradation of proteins in either the amygdala or insular cortex
      suffices for long-term stabilization of first-time encounter taste aversion. On
      the other hand, lactacystin applied in the insula, but not in the amygdala,
      before the second training prevented long-term storage of updated information.
      Our results support that degradation of proteins by means of the UPS is required
      every time taste aversion is to be stored in long-term memory.

PMID- 21193053
TI  - Vitamin D level after allogeneic hematopoietic stem cell transplant.
AB  - Vitamin D (VD) deficiency can cause osteomalacia, bone pain, muscle weakness,
      fatigue, and increased risk of fracture, and may precipitate or exacerbate
      osteopenia and osteoporosis. Patients receiving treatment for acute myeloid
      leukemia (AML) or acute lymphoblastic leukemia (ALL) may have limited exposure to
      sunlight and often experience gastrointestinal side effects that may decrease
      their ability to maintain an adequate VD level. We hypothesized that patients
      with AML and ALL would have a low VD level after allogeneic hematopoietic cell
      transplant (HCT), and that these patients would have a high incidence of
      osteoporosis/osteopenia. We therefore studied the incidence of low VD level and
      low bone mineral density after HCT. Of 289 patients with AML or ALL undergoing
      HCT between January 1, 2000, and January 31, 2009, at the Cleveland Clinic, 58
      (20.1%) patients had VD testing after HCT. Of these, 52 (89.7%) patients had a
      low VD level, and 6 (10.3%) had a normal level. Most patients with VD testing had
      graft-versus-host disease (GVHD) and were taking corticosteroids (94.8% and
      98.3%, respectively). Of the 49 patients with VD testing who also had bone
      mineral density testing, 65% had abnormal (low bone density) results. Only 21% of
      patients with VD testing were taking VD supplements prior to testing, and 65% had
      an elevated parathyroid hormone level. We found that most patients did not have
      VD testing after HCT, but those that did were very likely to have a low level and
      have low bone mineral density. Those with a low VD level were likely to have
      received corticosteroids, have GVHD, and have an elevated parathyroid hormone
      (PTH) level. Given the potential morbidity of low VD level, VD deficiency should
      be considered after HCT. Prospective study of VD level and its impact on
      morbidity and mortality after HCT is warranted.

PMID- 21193054
TI  - Use of matched unrelated donors compared with matched related donors is
      associated with lower relapse and superior progression-free survival after
      reduced-intensity conditioning hematopoietic stem cell transplantation.
AB  - As success of reduced-intensity conditioning (RIC) hematopoietic stem cell
      transplantation (HSCT) relies primarily on graft-versus-leukemia (GVL) activity,
      increased minor HLA disparity in unrelated compared to related donors could have
      a significant impact on transplant outcomes. To assess whether use of unrelated
      donors (URD) engenders more potent GVL in RIC HSCT compared to matched related
      donors (MRD), we retrospectively studied 433 consecutive T-replete 6/6 HLA
      matched URD (n = 246) and MRD (n = 187) RIC HSCT for hematologic malignancies at
      our institution. Diseases included: acute myelogenous leukemia (AML) (127), non
      Hodgkin lymphoma (NHL) (71), chronic lymphocytic leukemia (CLL) (68),
      myelodysplastic syndrome (MDS) (64), Hodgkin disease (HD) (40), chronic myeloid
      leukemia (CML) (25), multiple myeloma (MM) (23), myeloproliferative disorder
      (MPD) (12), acute lymphoblastic leukemia (ALL) (7), and other leukemia (1). All
      received uniform fludarabine and intravenous busulfan conditioning, and GVHD
      prophylaxis with tacrolimus/mini-methroxate (mini-MTX) or tacrolimus/sirolimus +/
      mini-MTX. Unrelated donors were younger compared to MRD (median donor age: 33
      years versus 52 years, P < .0001), and provided larger CD34(+) products (median
      CD34(+) cells infused: 8.7 * 10(6)/kg versus 7.5 * 10(6)/kg, P = .002).
      Distribution of diseases, disease risk, prior transplant, and cytomegalovirus
      (CMV) status was similar in both cohorts. Cumulative incidence of grade II-IV
      acute GVHD (at day +180), 2-year chronic GVHD, and 2-year nonrelapse mortality
      (NRM) were 20% versus 16%, 55% versus 50%, and 8% versus 6% in URD and MRD,
      respectively (P = NS). Cumulative incidence of relapse at 2 years was lower in
      URD, 52% versus 65% (P = .005). With median follow-up of 26.5 and 35.8 months, 2
      year progression-free survival (PFS) was significantly better in unrelated donor
      transplants, 39.5% for URD, and 29% for MRD (P = .01). Overall survival (OS) at 2
      years were 56% for URD versus 50% for MRD (P = .53). In multivariable analysis,
      URD was associated with a lower risk of relapse (hazard ratio [HR] 0.67, P =
      .002) and superior PFS (HR 0.69, P = .002). These results suggest that URD is
      associated with greater GVL activity than MRD, and could have practice changing
      impact on future donor selection in RIC HSCT.

PMID- 21193055
TI  - The outcomes of family haploidentical hematopoietic stem cell transplantation in
      hematologic malignancies are not associated with patient age.
AB  - Haploidentical hematopoietic cell transplantation (HCT) has been used to treat
      hematologic malignancies, but it is unknown whether the procedure is more
      effective in adults or children. To address this question, we analyzed patients
      aged 1 to 65 years old receiving myeloablative conditioning regimens followed by
      family 2 to 3 antigen HLA-mismatched HCT and reported to the Center for
      International Blood and Marrow Transplant Research (CIBMTR; n = 137) or performed
      in Dao-Pei Hospital in China, China (n = 181). The Dao-Pei cohort had more acute
      and chronic graft-versus-host disease (GVHD), less relapse, lower transplant
      related mortality (TRM), and better leukemia-free survival (LFS) than the CIBMTR
      cohort. Overall survival (OS) and outcomes were similar between adults and
      children. In the CIBMTR cohort receiving ex vivo T cell depletion (TCD), adults
      had higher TRM (relative risk [RR] 2.71, 95% confidence interval [CI] 1.29-5.69,
      P = .008) and lower OS (RR 1.75, 95% CI 1.08-2.84, P = .023) than children. In
      the CIBMTR subset that did not receive ex vivo TCD, relapse was lower in adults
      compared to children (RR 0.24, 95% CI 0.07-0.80, P = .020), but TRM, LFS, and OS
      were similar. We conclude that outcomes in adults and children are similar
      overall, although children have better survival than adults if ex vivo TCD is
      used.

PMID- 21193056
TI  - Donor lymphocyte infusion may reduce the incidence of bronchiolitis obliterans
      after allogeneic stem cell transplantation.
AB  - Bronchiolitis obliterans (BO) is a serious pulmonary complication after
      allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this study
      was to evaluate the diagnostic methods used, the incidence of BO, risk factors,
      and outcome in patients with BO at our center. The study included 527 HSCT
      patients transplanted between 1995 and 2003. Lung function tests (n = 1177) and
      risk factor analyses were performed in all patients. Chest X-rays and high
      resolution tomographies were investigated in patients with BO. The incidence of
      BO was 4.8%, as the diagnosis was established in 25 patients (4 children). Median
      time between HSCT and diagnosis of BO was 356 (84-1823) days. Eight patients
      (32%) had radiologic changes consistent with BO. Forced expiratory volume for 1
      second (FEV(1)) and forced expiratory flow at 50% (FEF(50)) and 75% (FEF(75)) of
      forced vital capacity (FVC) produced median values that were 49%, 25%, and 18% of
      the reference values at the time of BO diagnosis. FEF(75) was reduced before BO
      diagnosis in 7 patients (28%). In a multivariate risk factor analysis, chronic
      graft-versus-host disease (cGVHD) was found to be associated with BO (P < .001),
      whereas donor lymphocyte infusion (DLI) diminished the risk (P = .02). For 10
      patients with late BO (>1 year after HSCT), 80% survived 5 years after diagnosis,
      compared to 38% survival in 15 patients with early-onset BO (P = .06). We
      conclude that lung function tests with a persistent decrease in FEV(1) were more
      important than radiographic methods to recognize and monitor BO, that FEF(75) may
      serve as an early warning of BO, and that late-onset BO appears to be associated
      with better outcome. Chronic GVHD was confirmed as a risk factor, and
      administration of DLI may diminish the risk.

PMID- 21193057
TI  - Prediction of putative protein interactions through evolutionary analysis of
      osmotic stress response in the model yeast Saccharomyces cerevisae.
AB  - The osmotic stress response signalling pathway of the model yeast Saccharomyces
      cerevisae is crucial for the survival of cells under osmotic stress, and is
      preserved to varying degrees in other related fungal species. We apply a method
      for inference of ancestral states of characteristics over a phylogeny to 17
      fungal species to infer the maximum likelihood estimate of presence or absence in
      ancestral genomes of genes involved in osmotic stress response. The same method
      allows us furthermore to perform a statistical test for correlated evolution
      between genes. Where such correlations exist within the osmotic stress response
      pathway of S. cerevisae, we have used this in order to predict and subsequently
      test for the presence of physical protein-protein interactions in an attempt to
      detect novel interactions. Finally we assess the relevance of observed
      evolutionary correlations in predicting protein interactions in light of the
      experimental results. We do find that correlated evolution provides some useful
      information for the prediction of protein-protein interactions, but that these
      alone are not sufficient to explain detectable patterns of correlated evolution.

PMID- 21193058
TI  - Photocontrollable nitric oxide (NO) and nitroxyl (HNO) donors and their release
      mechanisms.
AB  - Nitric oxide (NO) and nitroxyl (HNO) are small-molecular, unstable compounds that
      mediate a variety of biological effects, especially in the cardiovascular system.
      Because of the instability of NO and HNO, controlled release for experimental
      investigation of their activities requires the use of appropriate donor
      molecules. Early donors released these molecules via spontaneous decomposition,
      but more recently, NO and HNO donors which can be controlled by photoirradiation
      have been developed; these are far superior, allowing precise spatial and
      temporal control of NO and HNO release. Among photocontrollable NO donors, metal
      nitrosyl complexes and nitroarene compounds are very important; the former
      releases NO by photoinduced cleavage of the metal-NO bond, and the latter, by
      photoisomerization of the aryl nitro group. Only a few photocontrollable HNO
      donors are available so far, and these are based on retro hetero Diels-Alder
      reaction initiated by photoabsorption. This review of photocontrollable NO and
      HNO donors and their mechanisms also covers spontaneous-release donors to the
      extent necessary to understand their contribution to the development of the
      photocontrollable donors.

PMID- 21193059
TI  - Transcriptional control mechanisms of genes of lipid and fatty acid metabolism in
      the Atlantic salmon (Salmo salar L.) established cell line, SHK-1.
AB  - The regulatory control mechanisms of lipid and fatty acid metabolism were
      investigated in Atlantic salmon. We identified sterol regulatory element binding
      protein (SREBP) genes in salmon and characterised their response, and the
      response of potential target and other regulatory genes including liver X
      receptor (LXR), to cholesterol and long-chain polyunsaturated fatty acids (LC
      PUFA) in the salmon established cell line, SHK-1. Two cDNAs for SREBPs homologous
      to mammalian SREBP-1 and SREBP-2 were characterised. We identified three groups
      of genes whose expression responded differently to the treatments. One group of
      genes, including cholesterol biosynthetic genes, showed increased expression in
      response to lipid depletion but supplementary cholesterol or LC-PUFA had no
      further effect. The expression of a second group of genes belonging to fatty acid
      biosynthetic pathways, included fatty acid synthase, Delta6 and Delta5 fatty acyl
      desaturases, also increased after lipid depletion but this was negated by
      cholesterol or by LC-PUFA supplementation. The expression of a third group of
      genes including acyl-CoA oxidase, HMG-CoA reductase and Elovl5 elongase was
      increased by cholesterol treatment but was not affected by lipid depletion or by
      LC-PUFA. This same pattern of expression was also shown by liver X receptor
      (LXR), indicating that acyl-CoA oxidase, HMG-CoA reductase and Elovl5 are
      possible direct targets of LXR. This suggests that salmon Elovl5 may be regulated
      differently from mammalian Elovl5, which is an indirect target of LXR, responding
      to LXR-dependent increases in SREBP-1.

PMID- 21193060
TI  - WITHDRAWN: Sex-differences in sodium/calcium exchange expression is a determinant
      of the arrhythmia phenotype in pre-pubertal rabbit hearts with Long QT type 2.
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- 21193061
TI  - Recording and interpreting unipolar electrograms to guide catheter ablation.

PMID- 21193062
TI  - A novel mechanism for LQT3 with 2:1 block: a pore-lining mutation in Nav1.5
      significantly affects voltage-dependence of activation.
AB  - BACKGROUND: SCN5A mutations that cause a gain of function in the cardiac voltage
      gated sodium channel (Nav1.5) lead to long QT syndrome and a higher risk for
      sudden cardiac death. OBJECTIVE: Here we functionally characterize the
      biophysical properties of the LQT3 variant, V411M, found in a newborn with a QT
      interval of 640 ms and 2:1 atrioventricular block. METHODS: Whole cell patch
      clamp was performed on wild-type and V411M Nav1.5 channels stably expressed in
      human embryonic kidney cells. RESULTS: V411M channels showed hyperpolarizing
      shifts in both the conductance-voltage (V(1/2) = -48.5 +/- 2.2 mV vs. -40.4 +/-
      1.6 mV for wild-type) and inactivation-voltage (-95.6 +/- 1.9 mV vs. -87.7 +/-
      1.7 mV) relationships, and a two-fold increase in late (sustained) sodium current
      during voltage ramp repolarizations. While neither mexiletine nor lidocaine
      exhibited potency differences between WT and V411M, or shortened the QTc in vivo,
      increased mutant block was observed with 10 MUM flecainide (71.4 +/- 3.0% vs.
      60.3 +/- 2.8%), in a voltage-dependent manner. Incorporation of V411M kinetics
      into atrial and ventricular action potential models reproduced prolonged action
      potential repolarization. CONCLUSIONS: Our data suggest a novel mechanism for
      LQT3, a result of a hyperpolarizing shift in the steady state activation
      relationship and re-activation of Nav1.5 towards a higher open probability during
      repolarization of the cardiac action potential. This results in an increased
      number of open-activated sodium channels, and so drugs that bind this state
      preferentially are expected to shorten the QTc more than those that favour the
      inactivated state.

PMID- 21193063
TI  - A prospective, randomized comparison of the acute hemodynamic effects of
      biventricular and left ventricular pacing with cardiac resynchronization therapy.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is most commonly performed
      with biventricular (BiV) pacing. Left ventricular (LV) only pacing is an
      alternative pacing configuration for CRT, but comparative studies with BiV pacing
      have shown inconsistent results. This may be due to differences in LV activation
      pattern, which could be differentially affected by atriventricular (AV)
      programming or atrial pacing (AP). OBJECTIVE: The purpose of this study was to
      compare AV optimization and the effect of atrial overdrive pacing on the acute
      hemodynamic response of LV and BiV CRT. METHODS: This study included 28 patients
      undergoing CRT. At implant, invasive LV dP/dt was measured by a micromanometer
      catheter during BiV or LV pacing in atrial sensing (AS) and AP modes at five
      different AV delays (AVDs), tested in randomized order. RESULTS: Compared with
      intrinsic rhythm, CRT with AS increased LV dP/dt by 12% +/- 10% during LV pacing
      and by 11% +/- 11% during BiV pacing (P = .15). With atrial overdrive pacing, CRT
      increased LV dP/dt by 17% +/- 10% with LV pacing and by 17% +/- 11% during BiV
      pacing (P = NS vs. LV; P <.001 vs. AS). The optimal AVD was significantly longer
      with AP (LV 202 +/- 63 ms vs. 131 +/- 42 ms during AS; BiV 195 +/- 71 ms vs. 134
      +/- 43 ms during AS) but did not differ between LV and BiV pacing. CONCLUSION: In
      this study, AP increases LV dP/dt during CRT but requires a substantially longer
      AVD. However, the optimal AVDs were similar for LV and BiV as were the magnitudes
      of the responses during CRT, suggesting that programmed AVDs are interchangeable
      in these two configurations.

PMID- 21193064
TI  - Atypical pacemaker-mediated tachycardia from the atrial channel: what is the
      mechanism?

PMID- 21193065
TI  - Sudden cardiac death, founder populations, and mushrooms: what is the link with
      gold mines and modifier genes?

PMID- 21193067
TI  - Deletion analysis of regions at the C-terminal part of
      cycloisomaltooligosaccharide glucanotransferase from Bacillus circulans T-3040.
AB  - Cycloisomaltooligosaccharide glucanotransferase (CITase) belongs to glycoside
      hydrolase family 66. According to the sequence alignment of enzymes in the same
      family, we divided the structure of CITase into five regions from the N terminus
      to the C terminus: an N-terminal conserved region (Ser1-Gly403), an insertion
      region (R1; Tyr404-Tyr492), two conserved regions (R2; Glu493-Ser596 and R3;
      Gly597-Met700), and a C-terminal variable region (R4; Lys701-Ser934). CITase
      catalyzes the synthesis of cycloisomaltooligosaccharides (CIs) with 7-17 glucose
      units (CI-7 to CI-17) from dextran. In order to clarify the functions of these C
      terminal regions (R1-R4), we constructed 15 deletion mutant enzymes. M123Delta
      (R4-deleted), MDelta234 (R1-deleted), and MDelta23Delta (R1/R4-deleted) catalyzed
      CI synthesis, but other mutants were inactive. M123Delta, MDelta234, and
      MDelta23Delta increased their K(m) values against dextran 40. The wild-type
      enzyme and M123Delta produced CI-8 predominantly, but MDelta234 and MDelta23Delta
      lost CI-8 production specificity. The k(cat) values of MDelta234 and
      MDelta23Delta decreased, and these mutants showed narrowed temperature and pH
      stability ranges. Our deletion analysis suggests that (i) R2 and R3 are crucial
      for CITase to generate an active form; (ii) both R1 and R4 contribute to
      substrate binding; and (iii) R1 also contributes to preference of CI-8 production
      and enzyme stability.

PMID- 21193066
TI  - Thibela TB: design and methods of a cluster randomised trial of the effect of
      community-wide isoniazid preventive therapy on tuberculosis amongst gold miners
      in South Africa.
AB  - BACKGROUND: South Africa has the third highest annual number of new tuberculosis
      (TB) cases globally. The resurgence of TB which has particularly affected gold
      miners in South Africa, is attributed to occupational risk factors for TB
      including silica dust exposure and high HIV prevalence. Isoniazid preventive
      therapy (IPT) is recommended for individuals at high risk to prevent both HIV
      related TB and silicotuberculosis, but global uptake has been poor. We describe
      the design of a cluster randomised study, "Thibela TB", which compares routine
      IPT targeted to those identified as at higher risk of TB (due to HIV infection or
      silicosis) against a "community-wide" approach in which IPT is offered to all
      employees. The trial is registered with the Current Controlled Trials:
      Registration number ISRCTN63327174. METHODS: We describe the rationale for the
      intervention of community-wide IPT, drawing on studies conducted in 1950-1960s in
      the pre-HIV era. The design of the study, including the definition of the
      cluster, is presented and advantages and limitations of such a design are
      discussed. CONCLUSION: If successful in reducing TB incidence and prevalence,
      this trial has potential to make a major contribution to TB control policy in
      high HIV settings, providing evidence concerning efficacy, and additionally
      safety and population-level effects on drug susceptibility patterns. Such
      rigorous evaluation is essential to provide policy makers with an evidence base
      to guide community-level TB prevention strategies.

PMID- 21193068
TI  - Molecularly designed alginate hydrogels susceptible to local proteolysis as three
      dimensional cellular microenvironments.
AB  - The development of sophisticated three-dimensional (3-D) cell culture
      microenvironments that recreate some of the complexity of the natural
      extracellular matrix (ECM) remains a challenging task. Here, the modification of
      alginate through partial crosslinking with a matrix metalloproteinase (MMP)
      cleavable peptide (proline-valine-glycine-leucine-isoleucine-glycine, PVGLIG) is
      described, and its use in the preparation of injectable, in situ crosslinkable
      hydrogel-like matrices is proposed. PVGLIG-grafted alginates were synthesized by
      carbodiimide chemistry and characterized. Their biological performance was
      evaluated by comparing the response of 3-D cultured mesenchymal stem cells (MSCs)
      to alginate hydrogels containing only cell-adhesion peptides (RGD-alginate) or
      both peptides (PVGLIG/RGD-alginate). After 1 week, cells remained essentially
      round within RGD-alginate, while they exhibited an elongated morphology within
      PVGLIG/RGD-alginate hydrogels, forming cellular networks. This suggests that
      cells were able to structurally reorganize the matrix, through enzymatic
      hydrolysis of PVGLIG residues, overcoming biophysical hydrogel resistance. As
      shown by gelatine-zymography, MSC presented higher activity of MMP-2 when
      cultured within alginate functionalized with MMP-sensitive peptide, suggesting
      that the cell's proteolytic phenotype was modulated by the matrix composition.
      Additionally, PVGLIG/RGD-alginate hydrogels were clearly degraded in cell
      culture. Taken together, the results demonstrate that the co-incorporation of MMP
      labile peptides in cell-adhesive RGD-alginate hydrogels improved their
      performance as ECM analogues, providing a more dynamic and physiological 3-D
      cellular microenvironment.

PMID- 21193069
TI  - RANKL-independent human osteoclast formation with APRIL, BAFF, NGF, IGF I and IGF
      II.
AB  - Non-canonical pathways of osteoclastogenesis have been described in which several
      cytokines are able to substitute for RANKL. These cytokines are few in number and
      their role(s) in pathological bone resorption has not been ascertained. We have
      identified five additional cytokines, APRIL, BAFF, NGF, IGF I and IGF II, that
      can induce RANKL-independent osteoclastogenesis. All five cytokines induced both
      osteoclast differentiation and activation with respect to the formation of
      significant numbers of TRAP(+) and VNR(+) multinucleated cells that were capable
      of resorbing bone. The number of TRAP(+) multinucleated cells that formed was in
      the range of 40-75% of that supported by MCSF plus RANKL. Resorption was at a
      similar level to that induced by the other known RANKL substitutes TNFalpha, IL-6
      and TGF-beta. The addition of osteoprotegrin, the endogenous decoy receptor of
      RANKL, revealed that this resorption was independent of RANKL. APRIL, BAFF, IGF I
      and IGF II were found to be expressed in giant cell tumour of bone. IGF I and IGF
      II demonstrated very strong expression in the stromal cell population of all
      tumour samples. This data suggests that non-canonical osteoclastogenesis plays a
      role in both normal and pathological bone resorption.

PMID- 21193070
TI  - 3D hierarchical geometric modeling and multiscale FE analysis as a base for
      individualized medical diagnosis of bone structure.
AB  - This paper describes a new alternative for individualized mechanical analysis of
      bone trabecular structure. This new method closes the gap between the classic
      homogenization approach that is applied to macro-scale models and the modern
      micro-finite element method that is applied directly to micro-scale high
      resolution models. The method is based on multiresolution geometrical modeling
      that generates intermediate structural levels. A new method for estimating
      multiscale material properties has also been developed to facilitate reliable and
      efficient mechanical analysis. What makes this method unique is that it enables
      direct and interactive analysis of the model at every intermediate level. Such
      flexibility is of principal importance in the analysis of trabecular porous
      structure. The method enables physicians to zoom-in dynamically and focus on the
      volume of interest (VOI), thus paving the way for a large class of investigations
      into the mechanical behavior of bone structure. This is one of the very few
      methods in the field of computational bio-mechanics that applies mechanical
      analysis adaptively on large-scale high resolution models. The proposed
      computational multiscale FE method can serve as an infrastructure for a future
      comprehensive computerized system for diagnosis of bone structures. The aim of
      such a system is to assist physicians in diagnosis, prognosis, drug treatment
      simulation and monitoring. Such a system can provide a better understanding of
      the disease, and hence benefit patients by providing better and more
      individualized treatment and high quality healthcare. In this paper, we
      demonstrate the feasibility of our method on a high-resolution model of vertebra
      L3.

PMID- 21193071
TI  - Cortical aspects of breathing control and sensation: a comment on von Leupoldt et
      al. (2010), "Cortical sources of the respiratory-related evoked potential".

PMID- 21193072
TI  - The freedom to seize a teachable moment.

PMID- 21193083
TI  - Creating a culture of civility takes a team.

PMID- 21193084
TI  - Working together to build a respectful workplace: transforming OR culture.
AB  - Respect is important in the creation of a positive perioperative work environment
      and effective OR teams. Low scores for respect in the OR on an employee opinion
      survey and responses on a more customized survey that examined issues associated
      with respect prompted leaders at the University Health Network to undertake a
      multiyear organizational strategy to address respect and quality of worklife
      initiatives. An interprofessional quality of worklife task force convened to
      create an action plan to address the outcomes of the surveys. The work of the
      task force included developing and implementing a code of conduct team charter
      for the OR, empowering leaders to better manage conflict through education and
      coaching, creating a collaborative, consistent approach to conflict resolution,
      and designing an education strategy for staff members to enhance communication
      and conflict resolution. Results of recent employee opinion surveys have
      reflected positive outcomes. Efforts to sustain the effects of the project
      include quarterly recognition awards and ongoing education focused on wellness
      and communication skills.

PMID- 21193085
TI  - Evolution and revision of the Perioperative Nursing Data Set.
AB  - The Perioperative Nursing Data Set (PNDS) is a nursing language that provides
      standardized terminology to support perioperative nursing practice. The PNDS
      represents perioperative nursing knowledge and comprises data elements and
      definitions that demonstrate the nurse's influence on patient outcomes. Emerging
      issues and changes in practice associated with the PNDS standardized terminology
      require ongoing maintenance and periodic in-depth review of its content. Like
      each new edition of the Perioperative Nursing Data Set, the third edition,
      published in 2010, underwent content validation by numerous experts in clinical
      practice, vocabulary development, and informatics. The goal of this most recent
      edition is to enable the perioperative nurse to use the PNDS in a meaningful
      manner, as well as to promote standardization of PNDS implementation in practice,
      both in written documentation and the electronic health record.

PMID- 21193086
TI  - Looking outside to meet internal challenges: the benefits of outsourcing.
AB  - Providing resourceful solutions to common facility management challenges can
      require many steps, including internal and external research, evaluating
      potential options, and implementing new protocols. The outpatient surgical
      services administrator at the Surgical Center of York and the Endoscopy Center of
      Memorial Hospital, York, Pennsylvania, addressed the challenge of managing and
      meeting surgeons' expectations and requests for better equipment and increased
      patient volume for ophthalmology procedures while maintaining a strict budget.
      Outsourcing of surgical equipment was identified as a viable option to meet these
      needs.

PMID- 21193087
TI  - Perioperative pharmacology: a framework for perioperative medication safety.
AB  - Learning pharmacology is a critical element of any health care practitioner's
      education to ensure quality and safety in perioperative care. The medication-use
      process and safe medication use are two important principles that contribute to
      the safe use of pharmacological agents in perioperative clinical practice. The
      medication-use process consists of procuring, prescribing, transcribing,
      dispensing, administering, and monitoring; however, variations in the medication
      use process result from demands unique to the perioperative environment, and
      these variations can sometimes bypass the safety nets within the system.
      Understanding these variances will help perioperative practitioners recognize
      threats to patient safety and help ensure the patient's well-being.
      Responsibilities of a safe medication-use system include assuring the public that
      practitioners use medications efficiently, safely, and effectively, and fully
      document all medications administered.

PMID- 21193088
TI  - Perioperative care of the patient with sickle cell disease.

PMID- 21193089
TI  - Instrument readiness: an important link to patient safety.

PMID- 21193092
TI  - Coming undone: failure of a closure device.

PMID- 21193095
TI  - Do positive psychosocial work factors protect against 2-year incidence of long
      term sickness absence among employees with and those without depressive symptoms?
      A prospective study.
AB  - OBJECTIVE: This study sought to examine the influence of protective work factors
      on long-term sickness absence among employees reporting different levels of
      depressive symptoms in a representative sample of the Danish workforce. METHODS:
      Questionnaire data were collected from a random sample of members of the Danish
      workforce aged between 18 and 64 years using information from two surveys with
      baselines in 2000 and 2005. From the year 2000 baseline, questionnaires from 5510
      employees (2790 males and 2720 females) were included; from the 2005 baseline,
      questionnaires from 8393 employees (3931 males and 4462 females) were included.
      Baseline data were collected on depressive symptoms, leadership, colleague
      support, and decision latitude. Information on 2-year incidence of sickness
      absence was derived from an official register. RESULTS: Stratified analyses on
      depressive symptom scores (none, moderate, and severe) indicate that quality of
      leadership was associated with reduced sickness absence to a somewhat stronger
      degree for those with moderate depressive symptoms (adjusted hazard ratio=0.88,
      95% confidence interval=0.78-0.98) than for those without depressive symptoms and
      that high decision latitude was associated with reduced sickness absence to a
      somewhat larger degree for those without depressive symptoms (adjusted hazard
      ratio=0.91, 95% CI=0.85-0.97) than for those with depressive symptoms. However,
      quality of leadership and decision latitude did not interact significantly with
      depressive symptom status. CONCLUSIONS: Quality of leadership may protect against
      long-term sick leave to a certain degree in those with moderate depressive
      symptoms. Possible interactions between psychosocial working conditions and
      depression status should be investigated in larger populations.

PMID- 21193096
TI  - The impact of attachment insecurity and sleep disturbance on symptoms and sick
      days in hospital-based health-care workers.
AB  - OBJECTIVE: Adult attachment insecurity is associated with many health outcomes
      and may be associated with sleep disturbance. The purpose of this study was to
      test the hypothesis that sleep disturbance mediates the relationship between
      attachment insecurity and three measures of health (perceived general health,
      physical symptoms and sick days) in a group that is at high risk of sleep
      disturbance: hospital based health-care workers. METHODS: One hundred thirty-one
      nondepressed female hospital workers completed self-report measures of adult
      attachment, sleep disturbance, depressive symptoms (excluding sleep-related
      items) and health outcomes. The hypothesis of mediation was tested with
      sequential regression analyses. RESULTS: Both attachment anxiety and attachment
      avoidance were significantly associated with impairment in global sleep quality
      (rho=.20 and .19, respectively, P<.05) and physical symptoms (rho=.21 and .19,
      P<.05). Attachment anxiety was also associated with depressive symptoms (rho=.33,
      P<.001) and sick days (rho=.21, P<.05). For both physical symptoms and sick days,
      mediation analyses were consistent with global sleep quality acting as a partial
      mediator of the relationship between attachment anxiety and physical health. Non
      sleep-related depressive symptoms were a stronger mediator. CONCLUSIONS: This
      study corroborates evidence that attachment insecurity is associated with sleep
      disturbance and extends this association to the occurrence of physical symptoms
      and time off work due to sickness among workers in a high-stress occupation.

PMID- 21193098
TI  - Underexposure to light at work and its association to insomnia and sleepiness: a
      cross-sectional study of 13,296 workers of one transportation company.
AB  - BACKGROUND: Light is a powerful synchronizer of the biological clock and of the
      sleep/wake cycle. Blind people have more sleep disturbances than people without
      eyesight problems. However, whether visually able people who are underexposed to
      bright natural light suffer from sleep wake disorders has never been examined.
      This study tried to assess the prevalence of sleep and wake disorders in subjects
      working in environments that are not exposed to natural light. METHODOLOGY: A
      setting-controlled cross-sectional epidemiological study was carried out. A
      representative sample of 13,296 French employees of a single transportation
      company participated in the study. During working hours, 4635 subjects (34.9%)
      experienced no light exposure (NLE) and 8661 were partially or completely exposed
      (LE) to natural light. Sleep disorders, sleep quality, and sleepiness were
      assessed using subjective tools: the Sleep Disorders Questionnaire-French version
      (SDQFV) and the Epworth Sleepiness Scale (ESS). Light exposure was estimated on
      workers' schedules and by objective measurements of light intensity (lux meter).
      PRINCIPAL FINDINGS: On a univariate analysis, complaints of poor sleep and
      sleepiness were significantly higher in NLE workers compared to LE:
      nonrestorative sleep (36.8% vs. 29.5%; P<.0001), insomnia (28.8% vs. 24.8%;
      P<.0001), severe insomnia (14.1% vs. 10.9%; P<.0001), and daytime somnolence
      (6.8% vs. 4.3%; P<.0001). After multivariate analysis, NLE has shown more
      insomnia (OR=1.8, 95% CI 1.3-2.3, P<.01) and hypersomnia (OR=1.9, 95% CI=1.3-2.4,
      P<.01) than LE. SIGNIFICANCE: These data suggest that underexposure to natural
      light at work may significantly impair sleep and wake disorders in non-light
      exposed workers.

PMID- 21193097
TI  - Frequency of bullying at work, physiological response, and mental health.
AB  - OBJECTIVE: The present study aimed to elucidate the relationship between bullying
      at work and cortisol secretion. Of particular interest was to examine whether
      frequently and occasionally bullied persons differed from nonbullied persons.
      METHODS: The study included 1944 employees (1413 women and 531 men) from 55
      workplaces in Denmark (16 private and 39 public workplaces). During a work day
      three saliva samples were collected at awakening, +30 min later, and at 20:00
      hours, and analyzed for cortisol concentrations. Mental health was assessed using
      items on somatic, cognitive, stress, and depressive mood. RESULTS: Of the 1944
      employees, 1.1% was frequently bullied and 7.2% occasionally bullied. Frequently
      bullied persons reported poorer mental health and had a 24.8% lower salivary
      cortisol concentration compared with the nonbullied reference group. Occasionally
      bullied persons had a poorer self-reported mental health, but their cortisol
      concentrations did not deviate from the group of nonbullied persons. The
      associations remained significant even after controlling for age, gender, exact
      time of sampling, mental health, and duration of bullying. Bullying occurred at
      78% of the workplaces (43 workplaces); frequent bullying occurred at 21% of the
      workplaces (40%). CONCLUSION: Frequent bullying was associated with lower
      salivary cortisol concentrations. No such association was observed for occasional
      bullying. Whether the generally lower secretion of cortisol among the frequently
      bullied persons indicate an altered physiological status remains to be evaluated
      in future studies. Yet, the physiological response seems to underscore the
      possibility that bullying indeed may have measurable physiological consequences.
      Hence, the physiological response supports the mental symptoms found among the
      frequently bullied.

PMID- 21193099
TI  - Health outcomes and self-labeling as a victim of workplace bullying.
AB  - OBJECTIVE: This study investigated the extent to which self-labeling as a victim
      of workplace bullying mediates or moderates the relationship between exposure to
      bullying and the target's health outcomes. METHODS: Data were collected by means
      of anonymous self-report questionnaires. A total of 1024 employees in a transport
      organization participated in the study, among whom 116 self-labeled victims were
      identified. Exposure to bullying was measured by a short version of the Negative
      Acts Questionnaire, while the respondents' health outcomes were measured by the
      Bergen Health Checklist. RESULTS: The findings showed that self-labeling both
      moderated and partially mediated the relationship between exposure to bullying
      and the targets' health. However, the moderator analyses indicate that self
      labeling only acts as moderator in cases of low exposure. Intense exposure to
      bullying behaviors is related to increased levels of health complaints regardless
      of the target's subjective appraisal of being a victim or not. CONCLUSION: Self
      labeling as a victim plays an important role in the victimizing process, although
      persistent exposure to workplace bullying seems to have considerable harmful
      effects on the target's health independently of whether the experience is labeled
      as bullying or not.

PMID- 21193100
TI  - Assessed and distressed: white-coat effects on clinical balance performance.
AB  - OBJECTIVES: While balance in young and older adults is known to change with the
      threat of standing on elevated surfaces, the potential for social anxiety to
      influence emotional states and balance performance during a clinical assessment
      is currently unknown. METHODS: Nineteen young and 19 older healthy female adults
      volunteered for the study. The effects of age and clinical assessment on balance
      performance were examined using a 2*2 between- and within-subjects factorial
      design. Balance performance measures were derived from forceplate recordings of
      three different postural tasks. Psychological measures included fear of negative
      evaluation, state anxiety, and fear related to the completed balance tasks.
      RESULTS: There was a significant increase in state anxiety and fear when
      participants performed balance tasks while being assessed by an evaluator.
      Compared to the control condition, both age groups leaned significantly further
      forward during the functional reach task when being assessed. While being
      assessed, older adults had significantly larger amplitudes and frequencies of
      center of pressure (COP) displacement during two-legged stance with eyes closed
      (EC) and significantly less stance time during one-legged standing compared to
      the control condition. In contrast, balance performance in young adults during
      one-legged or two-legged stance tasks was unchanged by clinical assessment.
      CONCLUSIONS: Social anxiety associated with the clinical assessment of balance
      can have a negative influence on both emotional states and balance control. As a
      result, clinicians need to recognize and account or control for potential social
      anxiety effects on clinical balance performance in young and older adults in
      particular.

PMID- 21193101
TI  - Impact of childhood trauma, alexithymia, dissociation, and emotion suppression on
      emotional Stroop task.
AB  - OBJECTIVE: Attentional bias to emotion- and illness-related information plays a
      prominent role in many mental disorders, particularly major depressive disorder
      and anxiety disorders. Using the emotional Stroop task we investigated which
      variables beyond aspects of patients' psychopathology might influence reaction
      times and interference in the Stroop test. METHODS: We investigated 82
      psychosomatic inpatients and 39 healthy controls. Diagnosis of depressive
      disorders, anxiety disorders, and somatoform disorders were established using the
      Structured Clinical Interview for DSM-IV. Severity of depression, anxiety,
      somatic symptoms, as well as experiences of childhood trauma, alexithymia,
      dissociation and emotion suppression were assessed via questionnaires. The
      emotional Stroop test was performed by using neutral and negative words, words
      related to depression, anxiety and somatization, respectively, and individually
      chosen words, which were related to the main problems of the participants.
      RESULTS: In multivariate regression analyses, reaction times were best predicted
      by self-reported experiences of childhood trauma. Interference, by contrast, was
      predicted by emotion suppression, but only for negative words, anxiety-related
      words and individually relevant words. Against our hypothesis, measurements of
      psychopathology were not associated with Stroop performance. CONCLUSIONS: The
      present study provides further support for the idea that the experience of
      childhood trauma influences adult neuropsychological performance. Furthermore,
      the findings suggest that the ability to suppress emotions may be an important
      predictor of attentional bias.

PMID- 21193102
TI  - Motor excitability during movement imagination and movement observation in
      psychogenic lower limb paresis.
AB  - BACKGROUND: Patients with a psychogenic paresis have difficulties performing
      voluntary movements. Typically, diagnostic interventions are normal. We tested
      whether patients with a psychogenic lower limb paresis exhibit abnormal motor
      excitability during motor imagery or movement observation. METHODS: Transcranial
      magnetic stimulation (TMS) with single and paired pulses was used to explore
      motor excitability at rest, during imagination of ankle dorsiflexions and during
      watching another person perform ankle dorsiflexions. Results obtained in ten
      patients with a flaccid psychogenic leg paresis were compared with a healthy age
      matched control group. In addition, results of two patients with a psychogenic
      fixed dystonia of the leg are presented. RESULTS: During rest, motor excitability
      evaluated by motor thresholds, size of motor-evoked potentials (MEP) by single
      pulse TMS, intracortical inhibition and intracortical facilitation tested by
      paired-pulse TMS were similar in patients and healthy subjects. MEPs recorded in
      five patients during movement observation were also comparable across the two
      groups. During motor imagery, patient MEPs were significantly smaller than in the
      control group and smaller than during rest, indicating an inhibition. CONCLUSION:
      In patients with motor conversion disorder, the imagination of own body movements
      induces a reduction of corticospinal motor excitability whereas it induces an
      excitability increase in healthy subjects. This discrepancy might be the
      electrophysiological substrate of the inability to move voluntarily. Watching
      another person perform movements induces a normal excitability increase,
      indicating a crucial role of the perspective and suggesting that focusing the
      patient's attention on a different person might become a therapeutic approach.

PMID- 21193103
TI  - Validation study of the Chinese version of the Illness Intrusiveness Ratings
      Scale.
AB  - OBJECTIVE: The Illness Intrusiveness Ratings Scale (IIRS) measures illness
      induced disruptions to 13 different aspects of lifestyles, activities, and
      interests. A stable three-factor structure has been well documented in studies
      conducted in Western countries. However, in Asia, the general validity of this
      scale has not been examined. METHODS: This study investigated the factor
      structure of the Chinese version of the IIRS in 641 inpatients at a Chinese
      hospital for cancer patients. The European Organization for the Research and
      Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) was also
      administered and compared with the IIRS. RESULTS: Exploratory principal component
      analysis identified a two-factor structure, "health and living" and
      "relationships and personal development", which accounted for 58.65% of the total
      variance. A "goodness-of-fit" test supported a two-factor solution (P=.070). The
      IIRS was significantly correlated with scores of every scale in the EORTC QLQ
      C30. CONCLUSION: These findings support the validity of the Chinese version of
      the IIRS but did not support a cross-cultural equivalence of the factor
      structure. This study was only performed in hospitalized cancer patients;
      therefore, further evaluation involving patients with other diseases is
      warranted.

PMID- 21193105
TI  - Instruments to measure sexual dysfunction in community and psychiatric
      populations.
AB  - Sexual dysfunction is a significant issue for many individuals. This can be the
      result of existing disorders, side effects of medications, or both. In order to
      effectively assess and, if appropriate, manage sexual dysfunction in various
      populations, it is important to consider the use of validated instruments that
      can provide a baseline to detect dysfunction and measure change over time. This
      review will assess the psychometric properties of scales (self-report and
      interview-based) that have been used in community, psychiatric, and gender
      specific populations, with a particular emphasis on depressed patients before and
      during antidepressant therapy. Key considerations for scale selection and
      development are also discussed.

PMID- 21193106
TI  - Introduction.

PMID- 21193104
TI  - Are the available apathy measures reliable and valid? A review of the
      psychometric evidence.
AB  - OBJECTIVE: Apathy is highly prevalent among neuropsychiatric populations and is
      associated with greater morbidity and worse functional outcomes. Despite this, it
      remains understudied and poorly understood, primarily due to lack of consensus
      definition and clear diagnostic criteria for apathy. Without a gold standard for
      defining and measuring apathy, the availability of empirically sound measures is
      imperative. This paper provides a psychometric review of the most commonly used
      apathy measures and provides recommendations for use and further research.
      METHODS: Pertinent literature databases were searched to identify all available
      assessment tools for apathy in adults aged 18 and older. Evidence of the
      reliability and validity of the scales were examined. Alternate variations of
      scales (e.g., non-English versions) were also evaluated if the validating
      articles were written in English. RESULTS: Fifteen apathy scales or subscales
      were examined. The most psychometrically robust measures for assessing apathy
      across any disease population appear to be the Apathy Evaluation Scale and the
      apathy subscale of the Neuropsychiatric Inventory based on the criteria set in
      this review. For assessment in specific populations, the Dementia Apathy
      Interview and Rating for patients with Alzheimer's dementia, the Positive and
      Negative Symptom Scale for schizophrenia populations, and the Frontal System
      Behavior Scale for patients with frontotemporal deficits are reliable and valid
      measures. CONCLUSION: Clinicians and researchers have numerous apathy scales for
      use in broad and disease-specific neuropsychiatric populations. Our understanding
      of apathy would be advanced by research that helps build a consensus as to the
      definition and diagnosis of apathy and further refine the psychometric properties
      of all apathy assessment tools.

PMID- 21193107
TI  - Coagulation update: what's new in hemostasis testing?
AB  - The current report provides a personal perspective summarising some interesting
      recent developments in hemostasis, as well as providing a brief glimpse into some
      possible imminent changes to come. We briefly review routine coagulation tests,
      and what changes may take place related to the new emerging anticoagulants. We
      also briefly review the old and new global tests of hemostasis, including
      thrombin generation and thromboelastography. Also briefly discussed within the
      diagnostics of bleeding and thrombotic disorders are the role of microparticles,
      the rise and fall of thrombophilia testing, the 'disappearance' of fibrinolysis
      pathway tests, and the absence of tests related to the endothelium, in part
      reflecting upon Virchow's triad.

PMID- 21193108
TI  - Rethinking the diagnosis of von Willebrand disease.
AB  - von Willebrand disease (VWD) is the most common inherited bleeding disorder and
      arises from deficiencies and/or defects in the plasma protein von Willebrand
      factor (VWF). VWD is classified into 6 different types, with type 1 identified as
      a (partial) quantitative deficiency of VWF, type 3 defined by a (virtual) total
      deficiency of VWF, and type 2 identifying four separate types (2A, 2B, 2M, 2N)
      characterised by qualitative defects. The classification is based on phenotypic
      assays including FVIII, VWF:Ag and VWF activity, typically by ristocetin cofactor
      (VWF:RCo), but also increasingly by collagen binding (VWF:CB). Phenotypic testing
      may be supplemented by multimer analysis, RIPA, and VWF:FVIII binding. Although
      genetic analysis is not required to diagnose VWD or to define a classification
      type, it may be useful in discrete situations. The current review briefly covers
      this diagnostic process, with a focus on newer approaches, including extended
      test panels and the use of data from desmopressin challenges as a diagnostic
      tool.

PMID- 21193109
TI  - Interaction between clinic and laboratory.
AB  - Clinicians order laboratory tests to diagnose, monitor, and screen for diseases,
      to evaluate or confirm previously abnormal results and to develop prognoses. The
      rigorous quality assurance programs, large automated processes and economic
      constraints may induce direct challenges to tailored diagnosis. Clinicians will
      have to gain an understanding of the underlying principles of laboratory
      technologies without losing their ability to practice 'the art of medicine' at
      their primary focus - the patient. Specialized laboratory services and expertise
      play especially important roles in coagulation hematology. Assays are technically
      demanding and often based on functional properties of proteins, producing results
      that are far more than plain numbers. Interpretation of laboratory data poses
      many challenges, such as pre-analytical and patient-dependent factors, of which
      the laboratory is often not well informed, but which the clinicians are required
      to take into account. The laboratory scientist needs to understand the multiple
      clinical circumstances causing variance or interference in the laboratory
      results. Direct interaction between clinic and laboratory is needed. When
      laboratory-specific issues are uncertain to the clinician, the laboratory
      scientist should become the clinician's primary consultant. The better the
      education and knowledge of both directions, the better the outcome. Regular
      multidisciplinary rounds by the clinicians and the laboratory scientists are of
      great benefit. This interaction at its best fosters research and development by
      identifying new mechanisms and tools.

PMID- 21193110
TI  - EUHASS: The European Haemophilia Safety Surveillance system.
AB  - Pharmacovigilance is an essential element of any drug treatment and considering
      the history of adverse events due to products used to treat inherited bleeding
      disorders, it should be an integral component of modern haemophilia treatment.
      Because inherited bleeding disorders and adverse events are rare, a multicentre,
      preferably multinational, adverse event reporting scheme for all clotting factor
      products is required. EUHASS is a European, prospective, multicentre adverse
      event reporting scheme in the field of inherited bleeding disorders.

PMID- 21193111
TI  - Platelet adhesion to collagen.
AB  - Platelets play a central role in maintaining hemostasis mainly by binding to
      subendothelial collagen exposed upon vascular injury, thereby initiating thrombus
      formation. Platelets can bind directly to the exposed collagen through two major
      receptors i.e. the integrin a2b1 and glycoprotein (GP) VI. However, under high
      shear conditions the GPIb-V-IX receptor complex and its main ligand von
      Willebrand Factor are additionally needed for firm platelet adhesion to the
      vessel wall. In this review, we summarize the current knowledge on the individual
      roles and structure-function relationships of these main platelet adhesion
      receptors.

PMID- 21193112
TI  - Platelet-derived microparticles - an updated perspective.
AB  - Platelet-derived microparticles (PMP) are a heterogeneous population of vesicles
      (< 1 mm) generated from the plasma membrane upon platelet activation by various
      stimuli. They are a discrete population differing from the exosomes which
      originate from the intracellular multivesicular bodies. PMP also differ from the
      microparticles derived from megakaryocytes despite the presence of several
      identical surface markers on the latter. The molecular properties and the
      functional roles of the PMP are beginning to be elucidated by the rapidly
      evolving research interest, but novel questions are simultaneously raised. This
      updated perspective discusses the most recent highlights in the PMP research in
      context with the methodological problems and the paradoxical role of the PMP in
      health and disease.

PMID- 21193113
TI  - Inflammation and coagulation. An overview.
AB  - Inflammation and coagulation are two main host-defence systems that interact with
      each other. Inflammation activates coagulation and coagulation modulates the
      inflammatory activity in many ways. The contributing molecular pathways are
      reviewed. Thrombin and activated protein C (APC) and its receptor EPCR constitute
      a major physiological regulatory system to control vascular wall permeability
      during sepsis. Pro-inflammatory cellular effects of coagulation proteases as well
      as the anti-inflammatory effects of APC/EPCR are mediated by signaling via
      protease activated receptors PAR on mononuclear cells, endothelial cells,
      platelets, fibroblast, and smooth muscle cells. The beneficial effects of APC in
      sepsis are mainly dependent on the PAR-mediated cell-protective properties rather
      than the anticoagulant protease function on coagulation cofactors FV/Va and
      FVIII/VIIIa. Animal experiments with signaling selective APC-variants show
      promise in improving the therapeutic efficacy and safety of APC in sepsis.

PMID- 21193114
TI  - Factor Xa and thrombin as targets for new oral anticoagulants.
AB  - Although currently available anticoagulants are effective for the prevention and
      treatment of thromboembolic disorders, they have several drawbacks. Low molecular
      weight heparin and fondaparinux produce a predictable level of anticoagulation
      that obviates the need for coagulation monitoring, but they must be given
      parenterally, which renders them inconvenient for long-term use. Vitamin K
      antagonists, such as warfarin, are administered orally, but produce a variable
      anticoagulant response because genetic polymorphisms, dietary vitamin K intake
      and multiple drug-drug interactions affect their metabolism. Consequently,
      coagulation monitoring and frequent dose adjustments are needed to ensure that a
      therapeutic level of anticoagulation is achieved. This is burdensome for patients
      and physicians, and costly for the healthcare system. These limitations have
      prompted the development of new oral anticoagulants that target thrombin or
      factor Xa. The new agents produce such a predictable anticoagulant response that
      they can be given in fixed doses without monitoring. This paper focuses on the
      new oral anticoagulants in the most advanced stages of development.

PMID- 21193115
TI  - Is PM a T2 (late translational) research journal?

PMID- 21193116
TI  - [What's new in clinical dermatology?].
AB  - What's new in clinical dermatology in 2010 mainly concerns inflammatory
      dermatosis (mainly eczema, psoriasis), internal medicine, allergology,
      infections. These last years, Tropical Infectiology concentrated news, which were
      widely reported in What's new in clinical dermatology in 2009. We have a special
      regard to clinical genetics, numerous papers having dismembered news clinical
      entities, or having improved knowledge on well known genodermatosis. Finally, we
      have a special chapter for clinical approach (patients selection, influences on
      clinical decision, duration of skin examination, Internet use, dermoscopy...),
      which has been largely investigated during these last years.

PMID- 21193117
TI  - [What's new in dermatological research?].
AB  - Dermatology research has been very rich this year, once again. The
      physiopathological mechanisms of paradoxical reactions to anti-TNF are better
      understood and new therapeutic targets for psoriasis have been evidenced.
      Targeted therapy in oncodermatology have shown their potential usefulness
      clinically but fundamental data have also clarified their mechanisms of action as
      well as their limits. The key role played by the immune system in nonsegmental
      vitiligo has also been clearly demonstrated. Fibroblasts as well as visible light
      seem to play a key role that has been poorly understood to date within the
      complex mechanisms of cutaneous pigmentation. Specific receptors of pruritus have
      been reported and foster hope for the development of more effective
      antipruriginous treatments in the near future. Other studies report new potential
      targets for diseases such as fungoid mycosis, atopic dermatitis, or scleroderma.
      Finally, physiopathological explanations have contributed to a variety of domains
      such as greying hair, axillary odors, HIV and herpes virus interrelations, and
      the teratogenicity of thalidomide.

PMID- 21193118
TI  - [What's new in paediatric dermatology?].
AB  - This paper summarizes a review of the medical literature focused on the field of
      pediatric dermatology from December 2009 to November 2010. Our objective was to
      select the papers published in the main journals of dermatology, internal
      medicine, pediatrics, infectious diseases and allergy that bring new information
      and significant advances concerning skin diseases in children. Recent advances in
      the field of infantile hemangiomas and atopic dermatitis are particularly
      detailed. This review also covers the main the following topics: psoriasis,
      Kawasaki disease, head lice and warts management, lichen, rare diseases such as
      epidermolyses bullosae.

PMID- 21193119
TI  - [New breakthroughs in Oncodermatology].
AB  - During this year 2010, Oncodermatology was again the object of numerous
      publications. From the analysis of articles published between October 2009 and
      October 2010, choices had to be made. Overall, update on skin cancer has been
      dominated this year by breakthroughs on melanoma, which blows a wind of hope
      raised by the results of several clinical trials. Among those, it could be shown
      for the first time that a molecule was able to increase the overall survival of
      our patients (Ipilimumab). Spectacular results have also been obtained using anti
      RAF. It seems that 2010 could be considered as a turning point in the therapeutic
      management of this cancer. In the field of lymphomas, several systemic treatments
      showed encouraging results in phase II and phase III trials.

PMID- 21193120
TI  - [What's new in dermatological treatments?].
AB  - Although the isolated clinical cases published are sometimes helpful in
      individual situations in which the therapeutic options have been exhausted, this
      type of publication cannot be generalized. For this reason, the selection
      presented covering the period from November 2009 to October 2010 is to a very
      large extent based on controlled trials, either because they contribute important
      information or because they raise great hope for a significant number of
      patients. For the first time in cutaneous oncology, a treatment (ipilimumab) has
      significantly increased overall survival in patients with metastatic melanoma
      (phase III), although this gain remains modest (4-6 months) and adverse
      immunological effects are frequent (30-40%). A phase I trial with treatment
      specifically targeting the mutant BRAF protein has shown an objective response in
      81% of the patients treated in the metastatic phase of melanoma, thus allowing
      its development to be pursued. Grouping two studies in a rare tumor such as
      dermatofibrosarcoma also gives hope with imatinib as a neoadjuvant treatment when
      the initial tumor is inoperable, with, however, an inconsistent response of
      approximately 50% and only if the tumor presents reorganization of chromosomes 17
      and 22. Cutaneous inflammatory diseases are still dominated by dual therapies in
      psoriasis, with, notably, an effectiveness trial on etanercept at different doses
      not showing a difference in efficacy depending on dose for the joint component of
      psoriasis, but also by the publication of a direct comparison of two dual
      therapies, ustekinumab versus etanercept. In atopic dermatitis, a controversial
      article invites one to reflect upon the progress made in the management of
      children by clinical nurses, as in the Netherlands and in Great Britain, in an
      attempt to contend with the shortage of dermatologists. Since the use of
      biotherapies is not the prerogative of psoriasis, infliximab was assessed in a
      phase II trial in Verneuil disease without demonstrating significant efficacy on
      the main criterion, but it did show a tendency to reduce the score used. This
      trial suffered from a weakness both in methodology and statistical power, thus
      precluding any conclusion. The rarity of therapeutic trials on drug eruptions
      warrants their mention. A French phase II study gives a glimpse of a trend toward
      efficacy in terms of survival in the treatment of toxic epidermal necrolysis with
      cyclosporine. As for infectious dermatosis and sexually transmitted infections, a
      French multicenter study has shown significantly higher efficacy with ivermectin
      than with malathion in treating pediculosis without increasing the side effects.
      Today, however, this systemic treatment cannot be a first-line treatment outside
      of certain specific situations. A large cohort study (somewhat unsatisfactory in
      its methodology) has not demonstrated the teratogenicity of antiherpes treatments
      in 830,000 infants. In prevention of HIV transmission, no microbicidal gel had
      shown efficacy to date. This has now been accomplished in South Africa with a 1%
      tenofovir gel. The results of a preliminary trial on therapeutic vaccination
      against HPV16 proposed to women who are carriers of cervical intraepithelial
      neoplasia opens the way for wide vaccine therapy of cutaneous virus-induced
      neoplasia. In conclusion, several articles analyzing the dermatology literature
      provide an opportunity to reflect on the quality of such articles, Boutron's
      being absolutely in-dis-pen-sa-ble!

PMID- 21193121
TI  - Pandemic 2009-2010 influenza vaccine: six lessons learned and the way forward
      (Allegro not Adagio).

PMID- 21193123
TI  - Fracture of the distal radius: risk factors for complications after locked volar
      plate fixation.
AB  - PURPOSE: To identify risk factors for complications after volar locking plate
      fixation of distal radius fractures. METHODS: We assessed early postoperative
      complications in 594 patients with fracture of the distal radius repaired with a
      volar locking plate and a minimum 1-month evaluation in the medical record. Later
      complications were assessed among 321 patients as a subset of the original cohort
      with a minimum 6 months' evaluation. We compared patient demographics, fracture
      characteristics, and aspects of management between patients with and without
      complications in bivariate analysis. Multivariable logistic regression analysis
      was applied to identify the factors independently associated with complications.
      RESULTS: A total of 47 complications were documented in the medical record. Early
      complications occurred in 24 of 594, including 8 intra-articular screws and 7
      patients with loss of fixation. Late complications occurred in 23 of 321,
      including 14 patients diagnosed with tendon irritation (one rupture of the flexor
      pollicis longus tendon) and 5 patients who had subsequent surgery to address
      dysfunction of the distal radioulnar joint (malunion, synostosis, and
      arthrofibrosis). Of the 47 complications, 26 were attributed to the plate, of
      which 9 were considered major (intra-articular screws and tendon rupture; 1.3% (8
      out of 594) and less than 1% (1 out of 321) of the early and late groups,
      respectively). In the logistic regression models, fall from a height and an
      ipsilateral elbow injury were positive independent predictors of early
      complications, whereas high-volume surgeons and plates other than the most
      commonly used plate were positive independent predictors of later complications.
      CONCLUSIONS: Volar locking plate fixation of distal radius fractures was
      associated with relatively few plate-related complications in our institutions.
      Factors indicating higher energy or complexity predicted early complications. The
      most common late complication was tendon irritation, which is less discrete and
      perhaps variably diagnosed. Further study is warranted regarding plate design and
      familiarity, which may help reduce complications. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Prognostic IV.

PMID- 21193124
TI  - Analysis of carpal malalignment caused by scaphoid nonunion and evaluation of
      corrective bone graft on carpal alignment.
AB  - PURPOSE: To clarify the correlation between a scaphoid deformity and carpal
      malalignment in patients with scaphoid waist nonunion and to investigate how
      accurately a corrective bone graft improves carpal malalignment according to the
      preoperative plan. METHODS: A total of 38 patients were analyzed retrospectively.
      Surgery was performed according to the anterior wedge bone graft method described
      by Fernandez. The scaphoid deformity and carpal malalignment were evaluated by
      the changes in the intrascaphoid angle (ISA) and axial length (AL) and by the
      changes in the radiolunate angle (RLA) and scapholunate angle (SLA),
      respectively, compared with the uninjured side by using standardized x-rays. Each
      variable was measured at 1 year after surgery. By performing multiple regression
      analysis, the correlation between the scaphoid deformity and carpal malalignment
      and between the correction of the scaphoid deformity and the change in carpal
      alignment were analyzed. RESULTS: Compared with the uninjured side, the mean
      respective changes in the ISA, AL, RLA, and SLA were 11 degrees , -1.3 mm, 14
      degrees , and 11 degrees , preoperatively. The changes in the RLA and SLA
      correlated with the change in the ISA, but not with the change in the AL. The
      mean postoperative corrections of the ISA and AL were 15 degrees  from full
      extension and 1.7 mm, and the changes in the RLA and SLA were 18 degrees  and 12
      degrees  from full extension, respectively. The change in the RLA correlated with
      the corrections of the ISA and AL. Although the change in the SLA did not
      correlate with either of them, the mean postoperative SLA was not significantly
      different from the mean value of the uninjured side. CONCLUSIONS: The degree of
      humpback deformity of the scaphoid correlated with the degree of carpal
      malalignment. The corrective bone graft resulted in the expected recovery of
      carpal alignment according to the preoperative plan. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Prognostic IV.

PMID- 21193125
TI  - The unstable nonunited scaphoid waist fracture: results of treatment by open
      reduction, anterior wedge grafting, and internal fixation by volar buttress
      plate.
AB  - PURPOSE: The purpose of this study is to evaluate the results of treatment of
      unstable nonunited scaphoid waist fracture by anterior wedge graft and internal
      fixation with the use of volar buttress plate and screws. METHODS: Fourteen adult
      male patients with unstable nonunited scaphoid waist fracture with a humpback
      deformity were treated by reduction of the collapse deformity, insertion of
      anterior wedge graft, and internal fixation with the use of volar buttress plate
      and screws. The mean patient age was 26 years, and the mean duration of the
      nonunion before surgery was 16.5 months. The follow-up time ranged from 9 to 19
      months (mean, 11 mo). Thirteen of the fourteen nonunions healed with sound
      radiographic union. Pre-existing avascular necrosis was a major adverse factor
      for achievement of union in one patient, even after a second bone-grafting
      procedure. RESULTS: Union was achieved in a mean of 3.8 months. Most of the
      patients had satisfactory correction of scaphoid deformity and the associated
      dorsal intercalated segment instability. Postoperatively, improvements were seen
      in the range of wrist flexion and extension, grip strength, and degree of dorsal
      intercalated segment instability. CONCLUSIONS: The results of the series suggest
      that the method of anterior wedge graft and internal fixation with the use of
      volar buttress plate and screws is effective for the treatment of unstable
      nonunited scaphoid waist fractures. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic
      IV.

PMID- 21193126
TI  - The scapholunate interosseous ligament afferent proprioceptive pathway: a human
      in vivo experimental study.
AB  - PURPOSE: To examine the afferent pathways of the scapholunate interosseous
      ligament (SLIL)-generated stimuli and their contribution to the overall carpal
      proprioception. METHODS: We examined 5 selected patients with preganglionic
      global root avulsion, confirmed by previous brachial plexus exploration, during
      the initial stage of carpal arthrodesis surgery. Despite their anesthetic-flail
      extremity, both the distal axon and the ganglionic cell were intact and able to
      transfer afferent stimuli. We placed electrodes subcutaneously over the adjacent
      areas of the ulnar, median, and radial nerves at the elbow region and performed
      an intraoperative neurophysiologic study. We studied the homologous sensory
      action potentials (SAPs) generated at the wrist in relaxation, flexion,
      extension, radial deviation, and ulnar deviation positions at each nerve and
      repeated them in 2 stages. The first took place with the SLIL intact and the
      second with the SLIL lacerated. The noise from the rest of the wrist elements was
      digitally eliminated. RESULTS: After the SLIL laceration, SAP intensities
      recorded at the median nerve in every wrist position were reduced. The radial and
      ulnar nerves showed differences of lesser degrees between the recorded SAP
      intensities before and after the ligament sectioning in every carpal position,
      with only the radial nerve following a specific pattern. The SAP intensity
      recorded at the median nerve in every carpal motion after the SLIL laceration was
      similar to the SAP intensity at relaxation with the SLIL intact, whereas
      recordings of various intensities were present for the radial and ulnar nerves.
      CONCLUSIONS: The SLIL generates proprioceptive stimuli at every wrist position.
      The main innervation of the whole SLIL derives from the anterior interosseous
      nerve; a partial contribution of the posterior interosseous nerve focused on the
      dorsal subregion of the ligament may also be present.

PMID- 21193127
TI  - Results of endoscopic carpal tunnel release relative to surgeon experience with
      the Agee technique.
AB  - PURPOSE: To establish the rate of iatrogenic injury after endoscopic carpal
      tunnel release (ECTR) for a surgeon in the first 2 years of practice; to report
      the rate of conversion from ECTR to open carpal tunnel release (OCTR), the reason
      for conversion, and any increase in morbidity found in patients converted to
      OCTR; and to determine whether the conversion rate decreased with increasing
      surgeon experience. METHODS: We conducted a retrospective review of patients
      undergoing ECTR by a single surgeon in the first 2 years of practice. Data
      collected or calculated included symptom relief, rate of conversion to OCTR,
      reason for conversion, and neurovascular complications. For patients converted to
      OCTR, we assessed satisfaction and function using the Disabilities of the Arm,
      Shoulder, and Hand questionnaire. We compared these results for 1 to 6 months, 7
      to 12 months, and 12 to 24 months to determine whether a learning curve was
      present. RESULTS: A total of 278 patients (358 procedures) underwent ECTR. Of
      these, 12 patients required conversion to OCTR during the index procedure over a
      2-year period. In the first 6 months of practice, 8 of 71 ECTRs were converted to
      OCTR compared to 1 of 72 in the second 6 months. This was a statistically
      significant decrease (p = .017). In year 2, 3 of 215 patients were converted to
      OCTR. Average Disabilities of the Arm, Shoulder, and Hand score for patients
      converted from ECTR to OCTR was 9. No patients required repeat surgery for
      recurrence of carpal tunnel symptoms. We observed no major neurovascular
      complications. CONCLUSIONS: A learning curve for ECTR was present. Rates of
      conversion significantly diminished with increased surgeon and anesthesia
      experience. Patients requiring conversion showed no variation in Disabilities of
      the Arm, Shoulder, and Hand scores from established values after OCTR. Patients
      may be at a higher risk of conversion to OCTR during the learning curve time
      period; nevertheless, we found no increased morbidity. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Prognostic III.

PMID- 21193128
TI  - Complication and revision rates following total elbow arthroplasty.
AB  - PURPOSE: To determine the complication rates after total elbow arthroplasty (TEA)
      in a large and diverse patient population. METHODS: We identified patients
      undergoing TEA as inpatients in the years 1995 to 2005 using California's
      Discharge Database. Short-term outcomes of interest included rates of infection
      or wound complications, revision, reoperation, and pulmonary embolism that were
      diagnosed during an inpatient hospital admission and mortality within 90 days of
      index surgery. Longer-term outcomes analyzed included rates of revision,
      amputation, and conversion to fusion. We used regression models to estimate the
      role of patient and provider characteristics in predicting the rates of adverse
      outcomes. RESULTS: We identified 1,625 patients undergoing TEA. Early
      complications, defined as those requiring inpatient re-admission within the first
      90 days after index surgery, were identified in 170 patients, and 132 patients
      required reoperation. Eighty one patients required revision in 90 days, and 48
      underwent revision within one year. Early infections and wound complications
      requiring readmission occurred in 88 patients. In the 90 days after surgery, 4
      patients had a pulmonary embolism and 10 patients died. One-hundred and twenty
      one patients required revision, amputation, or fusion during the observation
      period, with a mean follow-up of 4 years. Hospital volume was not associated with
      increased risk of adverse outcomes. CONCLUSIONS: We analyzed a large and diverse
      patient population undergoing TEA. The overall rate of short-term complications
      requiring inpatient treatment was high, at over 10% (170 patients), with almost
      8% (132 patients) requiring reoperation within the first 90 days. Although
      population-based studies have shortcomings, they can add to the body of knowledge
      of less frequent procedures such as TEA. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 21193129
TI  - Osteochondral lesions of the capitellum do not affect elbow kinematics and
      stability with intact collateral ligaments: an in vitro biomechanical study.
AB  - PURPOSE: Osteochondritis dissecans (OCD) of the capitellum most commonly affects
      adolescent pitchers and gymnasts, who present with pain and mechanical symptoms.
      Patients with larger lesions have poorer outcomes, possibly related to increased
      contact pressures on the surrounding articular surface with or without
      instability. The purpose of this in vitro study was to determine whether
      displaced OCD lesions of the capitellum lead to altered kinematics and stability
      of the elbow. METHODS: We mounted 9 fresh-frozen cadaveric arms in an upper
      extremity joint testing system, with cables attaching the tendons of the major
      muscles to motors and pneumatic actuators. An electromagnetic receiver on the
      ulna enabled quantification of the kinematics of the radius and ulna with respect
      to the humerus. We used 3-dimensional computed tomography scans and computer
      assisted techniques to navigate sequential osteochondral defects ranging in size
      from 12.5% to 100% of the capitellum. The arms were subjected to active and
      passive flexion in both the vertical and valgus positions with the forearm in
      both pronation and supination. RESULTS: We found no significant differences in
      valgus angulation or ulnar rotation between any of the OCD lesions and the intact
      elbow during flexion, regardless of arm position or forearm rotation.
      CONCLUSIONS: Osteochondritis dissecans lesions of the capitellum, both small and
      large, did not alter the ulnohumeral kinematics and stability with intact
      collateral ligaments. Therefore, excision of unfixable osteochondral fragments of
      the capitellum in the setting of intact collateral ligaments can be considered
      without the risk of creating instability.

PMID- 21193130
TI  - Effect of elbow and forearm position on contact pressure between the extensor
      origin and the lateral side of the capitellum.
AB  - PURPOSE: Bone-to-tendon contact in the origin of the common extensor tendons is
      considered to be one of the causes of lateral epicondylitis. Some factors,
      including elbow and forearm position, varus stress to the elbow, or contraction
      of the wrist extensor tendons, are considered to affect this bone-to-tendon
      contact. However, no studies have evaluated the effect of the elbow and forearm
      position on bone-tendon interface. The purpose of this study is to evaluate the
      effect of the position of the elbow and forearm on the contact pressure of the
      tendinous origin of the common wrist and finger extensors. METHODS: We used 8
      fresh cadaveric upper extremities. Contact pressure between the origin of the
      common extensor tendons and the lateral side of the capitellum was measured with
      a pressure sensor and was compared among various conditions, including elbow
      flexion angle (0 degrees , 30 degrees , 60 degrees , and 90 degrees ), forearm
      rotation position (neutral and 81.5 degrees  pronation position), and varus
      stress load of the elbow (none, gravity on the forearm, and gravity on the
      forearm +1.96 Nm). Contact pressure was also measured during tension force of the
      extensor carpi radialis longus, extensor carpi radialis brevis, and extensor
      digitorum communis by 0, 9.8, and 19.6 N. RESULTS: Contact pressure was
      significantly increased with the elbow extension position, forearm pronation
      position, and varus stress to the elbow under tension of the extensor carpi
      radialis longus or extensor carpi radialis brevis. CONCLUSIONS: This study
      provides data about the amount of contact pressure between bone and tendon at the
      origin of the common extensor tendons in the elbow. This information may lead to
      a better understanding of, and better treatment for, lateral epicondylitis.

PMID- 21193131
TI  - Foreign body reaction associated with Artelon: report of three cases.
AB  - The Artelon carpometacarpal joint implant is a degradable interposition
      arthroplasty spacer intended for use in thumb carpometacarpal joint
      osteoarthritis. Recently there have been reported cases of foreign body reaction
      attributed to the Artelon implant, which raise concerns about the use of this
      implant. The implant's manufacturers claim excellent biocompatibility. We report
      3 cases of persistent pain after thumb carpometacarpal joint arthroplasty
      performed using Artelon implants. In all 3 cases that required removal of the
      Artelon implant and trapeziectomy to achieve subsequent symptom relief, foreign
      body-type reaction associated with the Artelon was seen histologically.

PMID- 21193132
TI  - Extended step-advancement flap for avulsed amputated fingertip--a new technique
      to preserve finger length: case series.
AB  - PURPOSE: The conventional step-advancement flap does not restore fingertip length
      after avulsion amputation with projecting bone owing to the limited size of the
      distal triangular flap. To overcome this problem, the extended step advancement
      flap using the stepladder principle, described in this article, provides an
      extended distal triangular flap that can be wrapped around the projecting tip of
      the distal phalanx while avoiding longitudinal volar scarring. The purposes of
      this study were to present a modification of the original step-advancement
      technique and to report on results in 6 patients. METHODS: Between 2007 and 2009,
      6 men (mean age, 29 y; range, 18-45 y) presented with a large projecting tip of
      exposed bone of the distal phalanx after avulsion injury. All 6 had
      reconstruction using the described technique. After surgery, the finger was
      immobilized with a splint, followed by rehabilitation. During the follow-up of 9
      to 12 months, we clinically assessed flap-site skin quality, scar contractures,
      and finger mobility. We measured the finger's range of motion with a goniometer.
      Sensibility was evaluated using the static 2-point discrimination test. RESULTS:
      The postoperative course was uneventful. All flaps survived completely, except
      one that had mild marginal necrosis. We observed near-total active range of
      motion in all patients. The average static 2-point discrimination was 4 mm with a
      range of 3 to 5 mm. All patients resumed normal daily activities after 8 weeks.
      CONCLUSIONS: The extended step-advancement flap is ideal for closure of
      challenging fingertip amputation wounds because it maintains length and minimizes
      scars while providing a well-padded, sensate tip. It is a viable alternative to
      replantation of the fingertip. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 21193133
TI  - Boutonniere deformity.

PMID- 21193134
TI  - Early active short arc motion following central slip repair.
AB  - Open repairs of the central slip have traditionally been treated with 4 to 6
      weeks of immobilization, followed by therapy to restore motion. Although
      rehabilitative efforts were usually directed at avoiding extension lag, loss of
      flexion was also commonly encountered. Early active short arc motion produces
      improved range of motion with shorter treatment time compared with static
      immobilization of the repaired central slip. The technique is straightforward but
      its success depends on attention to the details of splinting and exercise, and
      the patient's active cooperation and compliance.

PMID- 21193135
TI  - Scope-assisted release of the cubital tunnel.
AB  - We report on a technique of endoscopic release of the cubital tunnel, which is a
      modification of Bruno and Tsai's technique. This article covers the history,
      complications, indications, and postoperative management of ulnar nerve
      entrapments treated endoscopically, with a special focus on our technique. This
      minimally invasive alternative to transposition requires no mobilization of the
      ulnar nerve, which could potentially reduce iatrogenic trauma to the nerve and
      its vascularity.

PMID- 21193136
TI  - Surgical management of primary thumb carpometacarpal osteoarthritis: a systematic
      review.
AB  - The aim of this article is to provide an updated systematic review on the 8 most
      commonly used surgical procedures to treat trapeziometacarpal osteoarthritis. A
      thorough literature search was performed using predetermined criteria. A total of
      35 articles fulfilled the inclusion criteria. Nine of these 35 articles were not
      included in previous systematic reviews. Systematic evaluation demonstrated the
      following: (1) there is no evidence that trapeziectomy or trapeziectomy with
      tendon interposition is superior to any of the other techniques. However, when
      interposition is performed, autologous tissue interposition seems to be
      preferable. (2) Trapeziectomy with ligament reconstruction or trapeziectomy with
      ligament reconstruction and tendon interposition (LRTI) is not superior to any of
      the other techniques. However, follow-up in the studies with a higher level of
      evidence was relatively short (12 mo); therefore, long-term benefits could not be
      assessed. In addition, trapeziectomy with LRTI seems associated with a higher
      complication rate. (3) Because the studies on thumb carpometacarpal (CMC)
      arthrodesis were of less methodological quality and had inconsistent outcomes, we
      are not able to conclude whether CMC arthrodesis is superior to any other
      technique. Therefore, high-level randomized trials comparing CMC arthrodesis with
      other procedures are needed. Nevertheless, findings in the newly included studies
      did show that nonunion rates in the literature are on average 8% to 21% and,
      complications and repeat surgeries are more frequent following CMC arthrodesis.
      (4) A study on joint replacement showed that total joint prosthesis might have
      better short-term results compared to trapeziectomy with LRTI. However, high
      level randomized trials comparing total joint prosthesis with other procedures
      are needed. In addition, there is no evidence that the Artelon spacer is superior
      to trapeziectomy with LRTI. We conclude that, at this time, no surgical procedure
      is proven to be superior to another. However, based on good results of CMC
      arthrodesis and total joint prostheses, we postulate that there could be
      differences between the various surgical procedures. Therefore randomized
      clinical trials of CMC arthrodesis and total joint prostheses compared to
      trapeziectomy with long follow-up (>1 y) are warranted.

PMID- 21193137
TI  - Current concepts of the anatomy of the thumb trapeziometacarpal joint.
AB  - This review article describes the anatomy of the thumb trapeziometacarpal joint.
      In the final phase of opposition screw home torque rotation of the volar beak of
      the thumb metacarpal in the pivot area of the trapezium recess and tension on the
      dorsal ligament complex create stability for power pinch and power grip. The
      resulting compressive shear forces can lead over time to trapeziometacarpal joint
      osteoarthritis.

PMID- 21193138
TI  - Technical use of synthetic conduits for nerve repair.

PMID- 21193139
TI  - [Emerging biomarkers for the diagnosis, staging and prognosis of prostate
      cancer].
AB  - The introduction and widespread adoption of prostate-specific antigen (PSA) has
      revolutionized the way prostate cancer is diagnosed and treated. However, the use
      of PSA has also led to overdiagnosis and overtreatment of prostate cancer
      resulting in controversy about its use for screening. PSA also has limited
      predictive accuracy for predicting outcomes after treatment and for making
      clinical decisions about adjuvant and salvage therapies. Hence, there is an
      urgent need for novel biomarkers to supplement PSA for detection and management
      of prostate cancer. A plethora of promising blood- and urine-based biomarkers
      have shown promise in early studies and are at various stages of development
      (Human kallikrein 2, Early Prostate Cancer Antigen, Transforming Growth Factor
      Beta 1 and Interleukin-6, Endoglin, PCA3, AMACR and ETS Gene Fusions). In this
      article, we review those biomarkers and then discuss the challenges a biomarker
      has to undergo before it is approved in a clinical use.

PMID- 21193140
TI  - [Postpartum urinary retention].
AB  - Postpartum urinary retention is an uncommon event that occurs in 0.7 to 0.9% of
      vaginal deliveries. An ignorance of this situation can lead to delayed diagnosis
      worsening the prognosis and to inadequate treatments. This complication is
      defined as the absence of spontaneous micturition within 6hours of vaginal
      delivery with a bladder volume above 400mL. The etiology depends on multiple
      factors. Because of physiological changes during pregnancy, the bladder is
      hypotonic with an increased post-void residual volume. The occurrence of a
      perineal neuropathy during delivery may cause a urinary retention. Risk factors
      are primiparity, prolonged labour, instrumental delivery and perineal
      lacerations. Treatment consists on clean intermittent catheterization and
      recovery occurs generally in 72hours. Persistent urinary retention is the
      principal short-term complication and should be treated by clean intermittent
      self-catheterization. Long-term consequences are poorly reported in the
      literature.

PMID- 21193141
TI  - [Recommendations for best practice for prostate biopsy].
AB  - OBJECTIVES: the aim of these recommendations is to help urologists to optimize
      prostate biopsy practice in order to improve diagnosis yield and to minimize
      associated morbidity. METHODS: online systematic literature search was performed
      on PubMed until April 2010. Regulation texts, published guidelines and results of
      recent urologists practice study, were taken into consideration. Level of
      evidence was assigned to each recommendation. RESULTS: patient information must
      be prior to the procedure and should be given through a medical exam by the
      physician performing the biopsies. The check for complication risk factors
      (allergic, infectious, hemorrhagic) had to be done preoperatively by the
      physician during the medical exam. The use of single systemic antibiotics is
      recommended and Quinolones are the drugs of choice (level of evidence 2).
      Biopsies should be performed on outpatient basis to assess the safety of the
      procedure. Transrectal route and ultrasound guidance are state-of-the-art. Local
      anaesthesia with peri-prostatic block is recommended (level of evidence 1). On
      baseline biopsies, extended 12-cores scheme should be performed. Urine retention
      and severe postbiopsies infections have been reported in less than 1% of cases.
      Optimal management of severe post-biopsies infections is based first on patient
      information and require hospital intravenous antibiotic therapy. CONCLUSION: to
      improve the sensitivity and to reduce the risk of complication, achievement of
      prostate biopsies should follow a standardized procedure.

PMID- 21193142
TI  - [Renal LESS surgery: Slight modification or surgical revolution?].
AB  - OBJECTIVE: to present our initial experience of laparoendoscopic single site
      (LESS) renal surgery. METHODS: between May 2009 and March 2010, nine
      nephrectomies and one cyst decortication were performed in nine patients. Eight
      of the procedures were done with three 5mm trocars inserted through a unique peri
      umbilical incision. In two cases, a specific single-port device was used. All
      operations were achieved with a 5-mm 30 degrees  lens and conventional
      laparoscopic instruments. The specimens were entrapped in a 10mm endoscopic bag
      and extracted through the umbilical incision. RESULTS: mean age was 56 years old.
      Mean BMI was 23.5 [19-34]. Mean operative time was 149min [80-240], and estimated
      blood loss was 90ml [20-250]. None of the patients required blood transfusion.
      Mean length of stay was 4.1 days [3-5]. Only one major complication occurred
      (functional occlusion). One conversion to conventional laparoscopy was necessary
      in a case of inflammatory kidney. Histologic exam showed benign lesions (cyst and
      non functional kidney) in seven cases, and papillary carcinoma in three cases.
      CONCLUSION: LESS surgery is feasible. Its advantages over conventional
      laparoscopy are not clear. LESS is a new procedure that should benefit from the
      improvement of technical instrumentation.

PMID- 21193143
TI  - [Preoperative assessment of renal vascular anatomy for donor nephrectomy: Is CT
      superior to MRI?].
AB  - BACKGROUND: computed tomography angiography (CTA) and magnetic resonance
      angiography (MRA) are both used in the preoperative assessment of vascular
      anatomy before donor nephrectomy. Our objective was to determine retrospectively
      and to compare the sensitivity of CTA and MRA imaging in preoperative renal
      vascularisation in living kidney donors. PATIENTS AND METHODS: between 1999 and
      2007, 42 kidney donors were assessed in our center: 27 by MRA, 10 by CTA, and
      five by both techniques. Images were interpreted using multiplanar
      reconstructions. Results were compared retrospectively with peroperative
      findings; discordant cases were re-examined by an experienced radiologist.
      Numbers of vessels detected with imaging methods was compared with numbers
      actually found at the operating time. RESULTS: MRA showed 35/43 arteries (Se 81.4
      %) and 33/34 veins (Se 97.1 %), and CTA showed 18/18 arteries (Se 100 %) and
      15/16 veins (Se 93.8 %). The presence of multiple arteries was detected in only
      one third of cases (3/9) on MRI scans; this difference was statistically
      significant. The missed arteries were not detected on second examination of the
      MRI scans with the knowledge of peroperative findings. CONCLUSION: MRA is less
      sensitive than CTA for preoperative vascularisation imaging in living renal
      donors, especially in the detection of multiple renal arteries.

PMID- 21193144
TI  - [In vitro study of the litholytic effects of herbal extracts on cystine urinary
      calculi].
AB  - INTRODUCTION: cystine stones represent 1% of urinary calculi in adults and 10% in
      children and are especially recurrent and resistant to ESWL. Medical therapy is
      often efficient but often poorly tolerated. In Morocco, various plants, Herniaria
      hirsuta, Opuntia ficus-indica, Zea mays and Ammi visnaga are proposed against
      nephrolithiasis. We assessed the effect of plant extracts on the disolution of
      cystine stones in vitro. MATERIAL AND METHOD: an extract of each plant was
      prepared by infusion of two grams of powdered plants during 30 minutes in 100ml
      of a boiled NaCl 9 g/L aqueous solution. Each extract was then filtered and
      thereafter set in a flask containing a cystine stone. The medium was maintained
      under stirring during 8 weeks. NaCl 9 g/L solution and sodium citrate 3 mmol/L
      solution were used as controls. At the end of each two weeks period, the stone
      was removed from the experimental medium and weighted after a 16h drying period
      at 40 degrees C. RESULTS: after 8 weeks of experiment, stone dissolution was
      complete for all herbal extracts, and was earlier in the presence of Zea mays (4
      weeks) or of Ammi visnaga (6 weeks) by comparison to only 18 +/- 8 and 20 +/- 1.5
      % for citrate and NaCl solutions, respectively. CONCLUSION: the studied herbal
      extracts were efficient for dissolving cystine stones, probably resulting from
      the formation of complexes between cystine and polyhydroxylated molecules present
      in the extracts. These results, to be confirmed in vivo, underline the potential
      interest of the plant extracts to treat cystine stones.

PMID- 21193145
TI  - [Modification of sexual desire and orgasm after radical prostatectomy for
      prostate cancer].
AB  - OBJECTIVES: To assess the impact of RP on patients' sexual desire and orgasm.
      MATERIAL AND METHODS: Prospective, cross-sectional survey using a 16-item self
      administered questionnaire. We assessed relevant domains of male sexual function
      (erectile function, sexual desire, and orgasm), psychological impact and
      treatment of ED. RESULTS: A total of 63 consecutive patients after RP were
      included (mean age: 63.9). Median time between questionnaire and RP was 26.8
      months (range 6-67). After RP, 74.6 % of patients used ED treatments. Lower
      sexual desire and intercourse frequency were reported in respectively 52.4 and
      79.4 %. Orgasm was modified in most patients: 39.7 % described loss of orgasm and
      38.1 % reported decreased intensity. Involuntary loss of urine at orgasm
      (climacturia) was reported in 25.4 %. Negative psychological impact was reported
      in 68.3 % (loss of self-esteem, loss of masculinity, anxiety). CONCLUSIONS: RP
      adversely affected erectile and orgasmic functions but also sexual desire, self
      esteem and masculinity despite treatments. Candidates for RP should be aware of
      ED but also of other postoperative sexual dysfunctions.

PMID- 21193146
TI  - [Spermatic cord sarcoma in adults: diagnosis and management].
AB  - PURPOSE: to clarify the patterns of diagnosis and management of adult spermatic
      cord sarcoma. PATIENTS AND METHODS: between 1996 and 2009, seven patients with
      spermatic cord sarcoma were treated at Cochin hospital. After updating the
      pathological diagnosis according to the new classification of sarcoma we found
      that all patients had well-differentiated or dedifferentiated liposarcoma. We
      analysed their clinical presentation, management and carcinological outcome.
      RESULTS: the patients' age ranged from 51 to 77 years, and their follow-up from 7
      to 68 months. In five patients, the diagnosis of well-differentiated liposarcoma
      (lipoma-like) with some dedifferentiated sectors was made straightaway. In the
      two other patients, the initial diagnosis was that of leiomyosarcoma, which was
      reconsidered as dedifferentiated liposarcoma according to the cytogenetical and
      immunohistochemical techniques available since 2005. In 6/7 patients, a tumour
      resection with an orchiectomy at the same time (four patients) or secondarily
      (two patients) was performed. In one patient, only a tumour resection, without
      orchiectomy, was made. Multiple recurrences were observed in the two patients who
      were initially diagnosed as leiomyosarcoma. They needed multiple reintervention.
      One of them died after 68 months of evolution, the other one was treated with
      chemotherapy and died after 47 months of evolution. Four patients are out of
      recurrence. One patient was lost to follow-up. CONCLUSION: the diagnosis of
      liposarcoma must be considered in all adult patients aged of more than 50 with
      fatty-shaped or containing fibomuscular nodules paratesticular tumours. The
      surgeon and the pathologist must be well informed and an early and wide resection
      of fatty masses of the sperm cord with negative margins is advocated. The quality
      of resection is crucial but its appreciation and carrying out are difficult. The
      role of complementary treatments, especially radiotherapy, has to be determined.

PMID- 21193147
TI  - [Female partners confronted with erectile dysfunction. A series of 137 patients].
AB  - AIM: To assess the behavior of female partners of patients consulting for
      erectile dysfunction (ED) and the impact of ED on their sex life. MATERIAL: One
      hundred and thirty seven men (mean age 57.4 ears), consulting for the first time
      because of ED and having a stable relationship with a single woman for more than
      six months, completed various questionnaires: IIEF, grounds for the possible
      absence of their partner during the consultation, attitude of the latter
      confronted with ED. The partners (mean age 54 years) have been invited to
      complete a questionnaire ISL (Index of Sexual Life) regarding their sexual life
      during the four last weeks. Seventy-nine (58%) have responded. RESULTS: Most
      often, the ED was severe (49%) and has evolved for more than one year (64%). The
      relationship has lasted for more than ten years for 77% of couples. Moreover, 43%
      of men declared that their partner had encouraged them to consult but 76%
      consulted alone the first time. According to the patients, the most frequent
      grounds for absence of their partner were: "she was occupied" (58%), "we did not
      think of it" (24%), "we did not know that it was possible" (15%). According to
      the patients, confronted with ED their partner was disappointed (29%), vexed
      (27%), frustrated (17%), accepting (15%) but the most often understanding (77%).
      The ISL scores were impaired in the different categories (sexual drive, sexual
      life satisfaction, general life satisfaction). According to ISL, 41% of women
      indicated that sexual intercourse was "a few times, almost never" or never
      satisfactory for them. Moreover, 45% found sexual intercourse "fairly enjoyable,
      enjoyable, or very enjoyable" but 41% did not feel an orgasm during vaginal
      penetration. Additionally, 44% remained "moderately or very satisfied" with their
      sexual relationship and 54% with their overall sex life. CONCLUSION: Few women
      attended the first consultation of ED because, according to the patients, usually
      they were not free. According to the patients, confronted with ED their partner
      was sometimes vexed, disappointed, frustrated but more often remained
      understanding. The analysis of the questionnaires ISL completed by the female
      partners shown that ED affected their sexuality but about half of them remained
      satisfied with their sexual relationship and overall sex life.

PMID- 21193148
TI  - [Assessment of sexual function in men with idiopathic Parkinson's disease using
      the International Index of Erectile Dysfunction (IIEF-15)].
AB  - OBJECTIVE: to assess the sexual function in men with idiopathic Parkinson's
      disease. PATIENTS AND METHODS: a cross-sectional study was performed in 35 men,
      mean age 68 +/- 9 years, with idiopathic Parkinson's disease followed in a single
      urological department. The 15 questions International Index of the Erectile
      Function was sent by postal mail. RESULTS: the answer's rate was 42.9% (15
      patients). The mean age of the responders was 68.7 +/- 10.0 years. Mean duration
      of the disease was 10.4 +/- 6.8 years. Sexual dysfunction was the second cause
      for consultation in urology. Despite a sustained sexual desire, patients had an
      altered sexual function with low erectile function, orgasmic function,
      intercourse satisfaction and total satisfaction scores. According to the
      Cappelleri's classification, the erectile dysfunction was severe in 54% of the
      cases and moderate in 26.6%. Age, institutionalization and overactive bladder
      symptoms were associated with erectile, orgasmic function and intercourse
      satisfaction alteration, sexual desire alteration, intercourse and global
      satisfaction alteration, respectively. CONCLUSION: men with idiopathic
      Parkinson's disease had a severe sexual dysfunction. The sexual desire was
      usually maintained but all the other domains were severely altered.

PMID- 21193149
TI  - [Flexible ureteroscopic lithotripsy in a 22-months-old child].
AB  - With the endourological development, the management of urinary tract calculi in
      children has significantly improved. The miniaturization of endoscopic equipment
      has allowed the use of flexible ureteroscopic with holmium YAG laser lithotripsy
      in children. We highlighted the case of a 22-month-old child, with an antecedent
      of megaureter, who had calculi in the right kidney lower pole. In collaboration
      with the urologist specialising in adult care, using an adapted technical tray,
      we underwent a laser intracorporeal lithotripsy using a 8 Charriere (Ch)
      ureteroscope and an holmium laser. No ureteral dilatation was required. A
      complete fragmentation of this infectious calculus was performed. This experience
      with a flexible ureteroscopy confirms that this technique is practicable,
      efficient and safe for stone treatment in children.

PMID- 21193150
TI  - [Metastatic pure testicular seminoma of the skin].
AB  - Seminomas are germinal tumors from testicular cells in men. Cutaneous metastasis
      are very rare. The authors report the case of a 56-year-old male patient admitted
      for treatment of an enlarged left testicular mass. Physical examination revealed
      a cutaneous nodule on the right side of the back. Histopathologic examination of
      both orchiectomy materiel and cutaneous lesion revealed pure seminoma. Chest and
      abdomen-pelvis CT revealed a pulmonary metastatic nodules, enlarged para-aortic
      lymph nodes and metastatic lesions in the adrenals glands. The patient died six
      months after diagnosis due to complications of metastatic disease despite
      adjuvant chemotherapy. To our knowledge, we report the first case demonstrating
      that seminoma may spread to skin.

PMID- 21193151
TI  - Cardiovascular diseases. Introduction.
AB  - Cardiovascular diseases (CVDs) account for ~30% of mortality, worldwide. Of the
      nine common risk factors for CVDs, the multinational INTERHEART study showed that
      dyslipidaemia, defined as an elevated apolipoprotein (apo) B:apoA1 ratio, is one
      of the most significant. The effective management of dyslipidaemia is therefore
      essential for the reduction of CV risk. It is well established that lowering low
      density lipoprotein-cholesterol (LDL-C) levels using statins significantly
      reduces the level of CV risk in people with dyslipidaemia. A meta-analysis of 14
      clinical trials, for example, demonstrated that each mmol/L reduction in LDL-C
      was associated with a 12% reduction in all-cause mortality, a 19% reduction in
      coronary mortality, and a 21% reduction in the total risk of major vascular
      events. Based on the results from this and similar studies, international
      treatment guidelines recommend lowering LDL-C to <2.0-2.6 mmol/L (<77-100 mg/dL)
      in patients with established CVDs and to <1.8-2.0 mmol/L (<70-77 mg/dL), where
      possible. Among the seven commonly used statins, pitavastatin is frequently used
      in Japan, South Korea, Thailand and China; it has recently been licensed for use
      in the USA and is now in the final stages of national approval within Europe. The
      following reviews discuss the safety and efficacy of pitavastatin for the
      treatment of dyslipidaemia relative to atorvastatin, simvastatin, and
      pravastatin, and examine its additional benefits beyond LDL-C reduction and its
      potential role in clinical practice.

PMID- 21193152
TI  - Pitavastatin - pharmacological profile from early phase studies.
AB  - Pitavastatin has been designed as a synthetic 3-hydroxy-3-methylglutaryl coenzyme
      A reductase inhibitor with a novel cyclopropyl moiety that results in several
      differences compared to other statins. These include effective inhibition of
      cholesterol synthesis and increased lipoprotein lipase expression at lower doses
      than other statins, and significant high-density lipoprotein-cholesterol and
      apolipoprotein A1-elevating activity that persists with time. The safety,
      tolerability and pharmacokinetics of pitavastatin and its major metabolite,
      pitavastatin lactone, have been investigated in a variety of patient groups with
      similar results, which suggests dosage adjustments are not required for gender,
      age or race. In healthy subjects, pitavastatin is well tolerated at the approved
      doses with no serious adverse events. The bioavailability of pitavastatin is, at
      60%, higher than that of any other statin and the majority of the bioavailable
      fraction of an oral dose is excreted unchanged in the bile. The entero-hepatic
      circulation of unchanged drug contributes to the prolonged duration of action and
      allows once-daily, any-time dosing. Pitavastatin is only slightly metabolised by
      cytochrome P450 (CYP) 2C9 and not at all by CYP3A4. Neither pitavastatin nor its
      lactone form, have inhibitory effects on CYP, and CYP3A4 inhibitors have no
      effect on pitavastatin concentrations. Moreover, P-glycoprotein-mediated
      transport does not play a major role in the drug's disposition and pitavastatin
      does not inhibit P-glycoprotein activity. Pitavastatin is transported into the
      liver by several hepatic transporters but OATP1B1 inhibitors have relatively
      little effect on plasma concentrations compared with other statins. In general,
      interactions, except with multi-transporter inhibitors like ciclosporin, are not
      clinically significant. Consequently, pitavastatin has minimal drug-food and drug
      drug interactions making it a treatment option in the large group of
      dyslipidaemic people that require multidrug therapy.

PMID- 21193154
TI  - Pitavastatin - from clinical trials to clinical practice.
AB  - Managing dyslipidaemia is central to the management of cardiovascular disease.
      Most statins can reduce the 5-year incidence of major vascular events by 20%. In
      Europe, however, up to 53% of statin-treated patients fail to attain their low
      density lipoprotein-cholesterol (LDL-C) target and residual risk remains high,
      even when targets are reached. Reasons for this include under-treatment due to
      insufficient starting doses/failure to uptitrate; poor persistence with therapy
      due to adverse events (AEs) or drug-drug interactions (DDIs); and failure to
      treat non-LDL-C risk factors, such as high triglycerides (TGs) and low high
      density lipoprotein-C (HDL-C). Phase III and IV studies demonstrate that
      pitavastatin 1-4 mg has a similar or greater lipid-lowering efficacy to
      atorvastatin 10-20 mg, simvastatin 20-40 mg and pravastatin 10-40 mg, and is well
      tolerated with a low incidence of adverse events (AEs). The SmPC recommends a
      usual starting dose of 1 mg, with dose-escalation if required. However, since the
      lower doses (1-2 mg) bring the majority of people with hypercholesterolaemia or
      combined dyslipidaemia to LDL-C target, the need for pitavastatin uptitration and
      the risk of under-treatment is low. In addition to reducing LDL-C, pitavastatin
      has a sustained beneficial effect on other atherogenic lipids, including TGs and
      HDL-C. Recent studies reveal that pitavastatin reduces coronary atheroma plaque
      volume as efficiently as atorvastatin and can improve the composition of coronary
      plaques, effects that are likely to reduce the risk of CV endpoints in patients
      with acute coronary syndrome. Moreover, pitavastatin has a number of pleiotropic
      effects that can reduce inflammation and lipid oxidation, improve endothelial
      function, reduce the metabolic changes associated with adiposity, and improve
      glucose metabolism and renal function. Compared to other statins, pitavastatin
      has a unique metabolic profile that could reduce the risk of DDIs, thereby
      providing a clear benefit in patients receiving polypharmacy. Overall,
      pitavastatin is a well tolerated and effective treatment for patients with
      hypercholesterolaemia and combined dyslipidaemia, especially in those with low
      HDL-C, and it should help improve LDL-C-target attainment rates by reducing the
      risk of under-treatment, minimising AE rates, and reducing the risk of DDIs in
      people requiring polypharmacy. Future and ongoing studies will directly compare
      the effects of pitavastatin vs. other statins on hard clinical endpoints.

PMID- 21193153
TI  - Pitavastatin - results from phase III & IV.
AB  - The pitavastatin Phase III and IV studies assessed the efficacy and safety of
      standard dose pitavastatin vs. comparable doses of alternative statins in a broad
      range of patients with hypercholesterolaemia. Phase III studies conducted in
      Europe included five 12-week, randomised, double-blind trials evaluating the non
      inferiority of pitavastatin 1-4mg vs. atorvastatin 10-20mg, simvastatin 20-40 mg
      and/or pravastatin 10-40mg in patients with primary hypercholesterolaemia and
      combined dyslipidaemia, including patients with high cardiovascular risk, type II
      diabetes, and age >=65 years. The primary endpoint was the adjusted mean percent
      change from baseline in low-density lipoprotein-cholesterol (LDL-C); secondary
      endpoints included changes from baseline in lipid and lipoprotein profiles, LDL-C
      target attainment rates and safety parameters. For each study, treatment was
      continued in open-label, long-term extension studies. Phase IV Japanese studies
      included CHIBA - a 12-week, open-label active control, non-inferiority
      investigator-led trial comparing the efficacy and safety of pitavastatin 2mg and
      atorvastatin 10 mg in patients with hypercholesterolaemia; PIAT - a 52-week open
      label, investigator-led, randomised, parallel-group study comparing the efficacy
      and tolerability of pitavastatin 2mg and atorvastatin 10 mg in patients with
      hypercholesterolaemia and glucose intolerance; and LIVES - a 2-year prospective
      post-marketing surveillance of pitavastatin in 20,279 patients with
      hypercholesterolaemia. The primary endpoint for the first two studies was the
      percent change from baseline in non-high-density lipoprotein-C (non-HDL-C) and
      HDL-C, respectively; secondary endpoints included % changes from baseline in
      other lipid/lipoprotein parameters, safety and tolerability. Overall, Phase III
      and IV studies demonstrate that pitavastatin 1-4mg is well tolerated, improves
      atherogenic lipid profile and increases LDL-C target attainment rates with a
      similar or greater efficacy to comparable doses of atorvastatin, simvastatin and
      pravastatin in most patient groups. In each of these studies, improvements in
      lipid profile were sustained or improved during the long term suggesting benefits
      for continued treatment with pitavastatin.

PMID- 21193155
TI  - Molecular and evolutionary analyses of formyl peptide receptors suggest the
      absence of VNO-specific FPRs in primates.
AB  - Formyl peptide receptors (FPRs) were observed to expand in rodents and were
      recently suggested as candidate vomeronasal chemosensory receptors. Since
      vomeronasal chemosensory receptors usually underwent positive selection and
      evolved concordantly with the vomeronasal organ (VNO) morphology, we surveyed
      FPRs in primates in which VNO morphology is greatly diverse and thus it would
      provide us a clearer view of VNO-FPRs evolution. By screening available primate
      genome sequences, we obtained the FPR repertoires in representative primate
      species. As a result, we did not find FPR family size expansion in primates.
      Further analyses showed no evolutionary force variance between primates with or
      without VNO structure, which indicated that there was no functional divergence
      among primates FPRs. Our results suggest that primates lack the VNO-specific FPRs
      and the FPR expansion is not a common phenomenon in mammals outside rodent
      lineage, regardless of VNO complexity.

PMID- 21193156
TI  - A genome wide association study between copy number variation (CNV) and human
      height in Chinese population.
AB  - Copy number variation (CNV) is a type of genetic variation which may have
      important roles in phenotypic variability and disease susceptibility. To hunt for
      genetic variants underlying human height variation, we performed a genome wide
      CNV association study for human height in 618 Chinese unrelated subjects using
      Affymetrix 500K array set. After adjusting for age and sex, we found that four
      CNVs at 6p21.3, 8p23.3-23.2, 9p23 and 16p12.1 were associated with human height
      (with borderline significant p value: 0.013, 0.011, 0.024, 0.049; respectively).
      However, after multiple tests correction, none of them was associated with human
      height. We observed that the gain of copy number (more than 2 copies) at 8p23.3
      23.2 was associated with lower height (normal copy number vs. gain of copy
      number: 161.2 cm vs. 153.7 cm, p = 0.011), which accounted for 0.9% of height
      variation. Loss of copy number (less than 2 copies) at 6p21.3 was associated with
      0.8% lower height (loss of copy number vs. normal copy number: 154.5 cm vs. 161.1
      cm, p = 0.013). Since no important genes influencing height located in CNVs at
      loci of 8p23.3-23.2 and 6p21.3, the two CNVs may cause the structural
      rearrangements of neighbored important candidate genes, thus regulates the
      variation of height. Our results expand our knowledge of the genetic factors
      underlying height variation and the biological regulation of human height.

PMID- 21193157
TI  - Identification of a novel mutation in POU3F4 for prenatal diagnosis in a Chinese
      family with X-linked nonsyndromic hearing loss.
AB  - We present the clinical and genetic findings for a Chinese family with X-linked
      non-syndromic hearing loss in which the affected males showed congenital profound
      sensorineural hearing impairment. In two affected brothers, the computer
      tomography of temporal bone showed bilateral dilation of the internal auditory
      canal with fistulous communication between the lateral canal and the basal
      cochlear turn, which is consistent with the typical DFNX2 phenotype. A missense
      mutation (c.647G->A) in the POU3F4 gene caused a substitution from glycine to
      glutamic acid at position 216 (p.G216E), and this mutation was found to
      consistently cosegregate with the deafness phenotype in the family. The mutation
      resulted in the loss of function of the POU3F4 by decreasing the affinity between
      the protein and DNA, as shown in silico by the structural analysis. Prenatal
      diagnosis of pregnant proband of this family revealed the c.647G->A mutation in
      DNA extracted from the amniotic fluid surrounding the fetus. The appropriate use
      of genetic testing and prenatal diagnosis plays a key role in reducing the
      recurrence of genetic defects in high-risk families.

PMID- 21193158
TI  - Additive and additive * additive interaction make important contributions to
      spikelets per panicle in rice near isogenic (Oryza sativa L.) lines.
AB  - Epistasis plays an important role in the genetic basis of rice yield traits.
      Taking interactions into account in breeding programs will help the development
      of high-yielding rice varieties. In this study, three sets of near isogenic lines
      (NILs) targeting three QTLs for spikelets per panicle (SPP), namely qSPP1, qSPP2
      and qSPP7, which share the same Zhenshan 97 genetic background, were used to
      produce an F(2) population in which the three QTLs segregated simultaneously. The
      genotypes of the individual F(2) plants at the three QTLs were replaced with
      three markers that are closely linked to the corresponding QTLs. These QTLs were
      validated in the F(2) and F(3) populations at the single marker level. qSPP7
      exhibited major pleiotropic effects on SPP, plant height and heading date.
      Multifactor analysis of variance was performed for the F(2) population and its
      progeny. Additive (additive interaction between qSPP2 and qSPP7 had significant
      effects on SPP in both the F(2) population and its progeny. Both additive and
      additive (additive interactions could explain about 73% of the total SPP
      phenotypic variance. The SPP performance of 27 three-locus combinations was
      ranked and favorable combinations were recommended for rice breeding in different
      ecosystems.

PMID- 21193159
TI  - Expression of a cotton MADS-box gene is regulated in anther development and in
      response to phytohormone signaling.
AB  - MADS-box gene family encodes a large number and variety of transcription
      regulators in plants. In this study, a cDNA, GhMADS9, encoding a typical MADS
      protein with 230 amino acids was isolated from cotton flower cDNA library.
      Subsequently, a 1,623 bp genomic DNA fragment of GhMADS9 gene was isolated in
      cotton by PCR. Compared with its cDNA sequence, six introns were found in GhMADS9
      gene. Fluorescent microscopy indicated that GhMADS9 protein localized in the
      nucleus. Transactivation activity assay in yeast cells revealed that GhMADS9
      protein did not show transcriptional activation. Quantitative RT-PCR analysis
      showed that GhMADS9 was specially expressed in cotton anthers. Further in situ
      hybridization analysis demonstrated that strong expression of GhMADS9 gene was
      detected in developing pollens, but no or weak signals were found in the other
      anther tissues. Furthermore, GhMADS9 expression was dramatically up-regulated in
      anthers with abscisic acid (ABA) treatment, whereas its activity was down
      regulated when treated by gibberellin (GA3). Collectively, our results suggest
      that GhMADS9 is a transcription factor and might be involved in cotton
      anther/pollen development and in response to ABA and GA3 signaling.

PMID- 21193160
TI  - The many faces of violence in emergency care.

PMID- 21193161
TI  - 2010 International Resuscitation Guidelines - time for a change?

PMID- 21193162
TI  - Threats and violence in the Swedish pre-hospital emergency care.
AB  - Although acts of threats and violence are problems that have received increased
      attention in recent years within Swedish pre-hospital care, only a handful of
      scientific studies have been carried out in this field. Threats and violence have
      a negative influence on the well-being of ambulance personnel. The aim in this
      study was both to investigate the incidents of threats and violence within the
      Swedish ambulance service and to describe these situations. Data was collected
      with questionnaires answered by 134 registered nurses and paramedics from 11
      ambulance stations located in four counties. The respondents' experiences of pre
      hospital care varied from 3 months to 41 years (mean=12 years, median=8 years).
      The results showed that 66% of the ambulance personnel experienced threats and/or
      violence during their work while 26% experienced threats and 16% faced physical
      violence during the last year. The most common kind of threat was threats of
      physical violence with 27% of the respondents experiencing threats involving
      weapons. Commonly occurring physical violence was in the form of pushes, punches,
      kicks and bites. In most cases, the perpetrator was the patient himself often
      under the influence of alcohol or drugs. The most serious situations occurred
      when the reason for raising the ambulance alarm was intoxication or a decreased
      level of consciousness.

PMID- 21193163
TI  - Patient-related violence at triage: A qualitative descriptive study.
AB  - AIM: The aim of the study was to describe the experiences of a group of triage
      nurses with patient-related workplace violence during the previous month.
      BACKGROUND: Globally and within the Australian health industry, nurses have been
      reported to be the occupation at most risk of patient-related violence, with
      triage nurses identified as a high risk group for both verbal and physical
      violence. METHOD: The study took place in the Emergency Department of a tertiary
      referral and teaching hospital in regional New South Wales, Australia. Data were
      collected from August to September 2008, and a qualitative descriptive
      methodology was employed. FINDINGS: The participants all reported experiencing
      episodes of patient related violence that were perceived as inevitable and
      increasing in intensity and frequency. Themes included identification of
      precipitating factors such as long waiting times and alcohol and substance
      misuse. Organisational issues included lack of aggression minimisation training;
      lack of formal debriefing following episodes of violence and frustration at
      lengthy reporting processes. CONCLUSION: In the context of the Emergency
      Department where patients present with a range of diagnoses and behaviours, it is
      unlikely that the issue of patient-related violence can be totally eliminated.
      However it can be prevented or managed more effectively on many occasions.
      Strategies to support staff and prevent and manage violence effectively should be
      a priority to provide a safe working environment and occupational health and
      safety for staff.

PMID- 21193164
TI  - The lived experience of victims of crime.
AB  - The focus of this research study was to ascertain the impact of crime on
      individuals, who presented with an injury to the emergency department. Given the
      high prevalence of crime in our society today, victims of crime are identified as
      a growing patient population seeking help in emergency departments. To maximise
      holistic care for these patients it is important that healthcare professionals
      gain insight into the experience of being a victim of crime. The study was
      qualitative in nature and used a phenomenological approach. In-depth,
      unstructured audio taped interviews were conducted to elicit the essence of the
      experience of being a victim of crime. The voices of the victims revealed four
      themes; "Fear, Shock and Disbelief", "Guilt/Self-blame", "Physical and
      Psychological Scars" and "Lifestyle Changes". The management of victims of crime
      in the emergency department appears to be concerned exclusively with physical
      injuries. Unseen is the potential psychological sequelae of the assault. Pivotal
      to these findings is the absence of psychological follow-up support for these
      victims of crime. This study affords healthcare professionals working in the
      emergency department, the opportunity to reflect upon current practice and
      highlight the value of their role in the provision of optimal care for this
      patient population.

PMID- 21193166
TI  - Investigating the factors affecting blood donation among Israelis.
AB  - AIM: This study examined whether the Theory of Planned Behavior adds
      significantly to the prediction of intention and actual blood donation of the
      general Israeli population. BACKGROUND: In most developed countries and in Israel
      in particular there is a chronic shortage of blood for transfusions. This raises
      questions about methods of increasing blood donations. DESIGN: This is a
      correlational quantitative study. METHODS: A questionnaire was created based on a
      review of the literature and the Theory of Planned Behavior. The questionnaire
      was distributed among a convenience sample of 190 Israeli Jewish men and women,
      aged 17-60. RESULTS: Israelis' perceived behavioral control of their blood
      donations, their subjective norms and their attitude regarding blood donation,
      predicted their intention to donate blood. It seems that intention predicted
      actual blood donations. A conspicuous finding is that members of the Ethiopian
      Jewish community displayed an extremely limited intention to donate blood.
      CONCLUSIONS: The results of this study show that a number of various educational
      and practical strategies may be used to encourage the population to donate blood.
      These include: reducing perceived barriers, directing interventions specifically
      at the population most likely to donate blood and forming a reserve of regular
      donors.

PMID- 21193165
TI  - Experiences of emergency care by the women exposed to acute physical intimate
      partner violence from the Finnish perspective.
AB  - BACKGROUND: In the acute trauma caused by intimate partner violence (IPV), the
      emergency department (ED) and its staff are often the first contact for women.
      The failure to intervene in IPV situations may contribute to further injury and
      health problems for women, as well as to frequent visits to the ED. AIMS: The
      aims of this study is to describe the history of IPV with its health consequences
      for women when seeking care for their acute injuries and what kinds of care
      experiences had the women had when visiting EDs. METHODS: Data were collected via
      questionnaires from 35 women and after that seven semi-structured interviews were
      conducted. The data were analyzed using quantitative and qualitative methods.
      RESULTS: Among the women the lifetime prevalence of physical IPV was 94%. Ninety
      seven percent of past and 56% of acute cases of physical violence were
      accompanied by psychological violence. The surveyed women highlighted individual
      needs for care, including appropriate medical care of injuries, and psychological
      and tangible support. The women worried about their children and partners and
      regarded supporting the whole family as important. CONCLUSION: There is a need
      for ED professionals to develop family-oriented services, and a need for further
      training and research on how to deal with women exposed to IPV.

PMID- 21193167
TI  - Perceived facilitators and barriers to clinical clearance of the cervical spine
      by emergency department nurses: A major step towards changing practice in the
      emergency department.
AB  - OBJECTIVES: We conducted a validation study on use of the Canadian C-Spine Rule
      (CCR) by emergency department (ED) nurses to clear the c-spine in alert and
      stable trauma patients (N=3633). This survey sought to identify potential
      facilitators and barriers to an implementation policy that would allow nurses to
      clinically clear the c-spine of minor trauma patients. METHODS: We conducted a
      prospective quantitative survey of ED nurses in six hospitals. Questions were
      developed from a previous qualitative survey at the same validation study EDs.
      RESULTS: 158 ED nurses were surveyed and 137 (86.7%) responded. Nurses strongly
      endorsed potential facilitators for nursing clearance of the c-spine, including
      'Like to try new things at work' (96.4%) and 'Easy for me to take on new
      responsibilities' (96.4%). Most respondents were comfortable applying the rule
      (89.1%). Nurses endorsed potential barriers but at much lower rates, with the
      most common being 'Heavy workload makes it difficult to use the rule' (37.2%).
      Variation existed among hospitals for the facilitator 'Use of the rule would be
      useful to my practice', ranging from 81.8% to 100% endorsement (P=0.004).
      CONCLUSIONS: This survey was an important step towards the goal of empowering ED
      nurses to clinically clear the c-spine of alert and stable trauma patients. There
      was a high rate of endorsement of facilitators and a low rate of endorsement of
      barriers. We found variation between hospitals, emphasizing the importance of
      understanding local beliefs when seeking to change clinical practice. We are
      conducting an implementation trial based on this feedback.

PMID- 21193168
TI  - Stroke thrombolysis: Barriers to implementation.
AB  - Stroke is a frequent emergency faced by Emergency Department (ED) staff. Evidence
      produced from significant trials has led to the introduction of stroke
      thrombolysis across the world. Campaigns to increase public awareness that
      'stroke is a medical emergency,' have led to emergency departments facing
      necessary adjustment, re-allocation of resources and education of staff. From a
      review of the associated literature, barriers to implementation of the service
      include; non-recognition of stroke, inappropriate triage of these patients by
      both ED staff and ambulance personnel, delays in obtaining neuro-imaging, and
      inefficient processes of in-hospital emergency stroke care. Further study is
      required to review the educational needs and resource management, as well as the
      efficacy of the public education in stroke.

PMID- 21193169
TI  - Getting to the cause of a fall - An unusual case.

PMID- 21193170
TI  - Immunocompetent cells and cytokine expression in the rat periodontal ligament at
      the initial stage of orthodontic tooth movement.
AB  - OBJECTIVE: The aim of the present study is to investigate the involvement of
      immunocompetent cells, pro-inflammatory cytokines and HSP, to evaluate a change
      of periodontal ligament during the initial stage of orthodontic tooth movement.
      DESIGN: In the present study, we investigated the distributional density of
      immunocompetent cells, the localisation of cytokines, and the expression levels
      of their mRNA in the periodontal ligament during the initial stage of orthodontic
      tooth movement, using immunohistochemistry and real-time PCR. RESULTS:
      Orthodontic tooth movement led to significant recruitment of OX6(+) cells and
      ED1(+) cells in the rat PDL. Double-immunofluorescence staining showed that some
      ED1(+) cells expressed pro-inflammatory factors of IL-1beta and TNF-alpha in the
      PDL during orthodontic tooth movement. Real-time PCR analysis revealed that the
      expression levels of IL-1beta (Il1b) and TNF-alpha (Tnf) mRNA gradually increased
      following its decrease after 1h of orthodontic tooth movement. These findings
      suggest that ED1(+) cells are involved in the expression of TNF-alpha and IL
      1beta and the subsequent regulation of bone resorption on pressure side. HSP27
      (Hspb1) mRNA levels were significantly increased as compared with the control at
      1h of the initial stage of treatment. CONCLUSION: ED1(+) cells involved in the
      expression of TNF-alpha and IL-1beta may play an important role in the initial
      reaction of the PDL and in the induction of the osteoclastic bone resorption
      during orthodontic tooth movement.

PMID- 21193171
TI  - Inattention, but not OCD, predicts the core features of hoarding disorder.
AB  - Hoarding Disorder (HD), defined as the acquisition of and failure to discard
      large volumes of possessions, resulting in clutter that precludes normal use of
      living spaces, is a common and debilitating condition. Although hoarding has
      historically been conceptualized as a variant of obsessive-compulsive disorder
      (OCD), increasing evidence suggests that hoarding might be more closely
      associated with the symptoms of attention deficit-hyperactivity disorder (ADHD).
      The aim of the present study was to clarify the relationship between the core
      features of hoarding (clutter, difficulty discarding, acquiring), OCD symptoms,
      and ADHD symptoms. HD (N = 39), non-hoarding OCD (N = 26), and healthy control (N
      = 36) participants underwent careful diagnostic interviewing and completed
      standardized self-report measures of the core features of hoarding (clutter,
      difficulty discarding, acquiring), OCD symptoms, negative affect, and the
      inattentive and hyperactive/impulsive symptoms of ADHD. Multiple linear
      regressions demonstrated that after controlling for global negative affect, OCD
      symptoms did not significantly predict any of the core features of HD.
      Conversely, the inattentive (but not hyperactive/impulsive) symptoms of ADHD
      significantly predicted severity of clutter, difficulty discarding, and
      acquiring. These results challenge current conceptualizations of hoarding as a
      subtype of OCD, and suggest an association with neurocognitive impairment.

PMID- 21193172
TI  - Methylphenidate but not atomoxetine or citalopram modulates inhibitory control
      and response time variability.
AB  - BACKGROUND: Response inhibition is a prototypical executive function of
      considerable clinical relevance to psychiatry. Nevertheless, our understanding of
      its pharmacological modulation remains incomplete. METHODS: We used a randomized,
      double-blind, placebo-controlled, crossover design to examine the effect of an
      acute dose of methylphenidate (MPH) (30 mg), atomoxetine (ATM) (60 mg),
      citalopram (CIT) (30 mg), and placebo (PLAC) (dextrose) on the stop signal
      inhibition task in 24 healthy, right-handed men 18-35 years of age. Participants
      performed the task under each of the four drug conditions across four consecutive
      sessions. RESULTS: Methylphenidate led to a reduction in both response time
      variability and stop-signal reaction time (SSRT), indicating enhanced response
      inhibition compared with all other drug conditions. Crucially, the enhancement of
      response inhibition by MPH occurred without concomitant changes in overall
      response speed, arguing against a simple enhancement of processing speed. We
      found no significant differences between ATM and PLAC, CIT and PLAC, or ATM and
      CIT for either response time variability or SSRT. CONCLUSIONS: An acute dose of
      MPH but not ATM or CIT was able to improve SSRT and reduce response time
      variability in nonclinical participants. Improvements in response inhibition and
      response variability might underlie the reported clinical benefits of MPH in
      disorders such as attention-deficit/hyperactivity disorder.

PMID- 21193173
TI  - A common genetic variant in the neurexin superfamily member CNTNAP2 is associated
      with increased risk for selective mutism and social anxiety-related traits.
AB  - BACKGROUND: Selective mutism (SM), considered an early-onset variant of social
      anxiety disorder, shares features of impaired social interaction and
      communication with autism spectrum disorders (ASDs) suggesting a possible shared
      pathophysiology. We examined association of a susceptibility gene, contactin
      associated protein-like 2 (CNTNAP2), for ASDs and specific language impairment
      with SM and social anxiety-related traits. METHODS: Sample 1 subjects were 99
      nuclear families including 106 children with SM. Sample 2 subjects were young
      adults who completed measures of social interactional anxiety (n = 1028) and
      childhood behavioral inhibition (n = 920). Five single nucleotide polymorphisms
      in CNTNAP2 (including rs7794745 and rs2710102, previously associated with ASDs)
      were genotyped. RESULTS: Analyses revealed nominal significance (p = .018) for
      association of SM with rs2710102, which, with rs6944808, was part of a common
      haplotype associated with SM (permutation p = .022). Adjusting for sex and
      ancestral proportion, each copy of the rs2710102*a risk allele in the young
      adults was associated with increased odds of being >1 SD above the mean on the
      Social Interactional Anxiety Scale (odds ratio = 1.33, p = .015) and
      Retrospective Self-Report of Inhibition (odds ratio = 1.40, p = .010).
      CONCLUSIONS: Although association was found with rs2710102, the risk allele (a)
      for the traits studied here is the nonrisk allele for ASD and specific language
      impairment. These findings suggest a partially shared etiology between ASDs and
      SM and raise questions about which aspects of these syndromes are potentially
      influenced by CNTNAP2 and mechanism(s) by which these influences may be conveyed.

PMID- 21193175
TI  - Synthesis of C-glycosylated amino acids by hetero-Diels-Alder addition of ethyl 2
      nitrosoacrylate to exo-glycals.
AB  - C-Glycoamino acids bearing a variety of sugar moieties were prepared by the
      hetero-Diels-Alder addition of ethyl 2-nitrosoacrylate to exo-glycals. The
      reaction proceeds smoothly to yield spirocyclic oxazines that can be converted
      into useful products by several hydrogenolytic techniques.

PMID- 21193174
TI  - Brain network connectivity in individuals with schizophrenia and their siblings.
AB  - BACKGROUND: Research on brain activity in schizophrenia has shown that changes in
      the function of any single region cannot explain the range of cognitive and
      affective impairments in this illness. Rather, neural circuits that support
      sensory, cognitive, and emotional processes are now being investigated as
      substrates for cognitive and affective impairments in schizophrenia, a shift in
      focus consistent with long-standing hypotheses about schizophrenia as a
      disconnection syndrome. Our goal was to further examine alterations in functional
      connectivity within and between the default mode network and three cognitive
      control networks (frontal-parietal, cingulo-opercular, and cerebellar) as a basis
      for such impairments. METHODS: Resting state functional magnetic resonance
      imaging was collected from 40 individuals with DSM-IV-TR schizophrenia, 31
      siblings of individuals with schizophrenia, 15 healthy control subjects, and 18
      siblings of healthy control subjects while they rested quietly with their eyes
      closed. Connectivity metrics were compared between patients and control subjects
      for both within- and between-network connections and were used to predict
      clinical symptoms and cognitive function. RESULTS: Individuals with schizophrenia
      showed reduced distal and somewhat enhanced local connectivity between the
      cognitive control networks compared with control subjects. Additionally, greater
      connectivity between the frontal-parietal and cerebellar regions was robustly
      predictive of better cognitive performance across groups and predictive of fewer
      disorganization symptoms among patients. CONCLUSIONS: These results are
      consistent with the hypothesis that impairments of executive function and
      cognitive control result from disruption in the coordination of activity across
      brain networks and additionally suggest that these might reflect impairments in
      normal pattern of brain connectivity development.

PMID- 21193176
TI  - The relationship between alexithymia and psychological factors in systemic lupus
      erythematosus.
AB  - BACKGROUND: Alexithymia has been described as an important dimension in several
      medical diseases. Systemic lupus erythematosus (SLE) is a chronic condition
      characterized by unpredictable clinical manifestations. Our aim is to reveal
      which factors (psychological factors and quality of life dimensions) are
      associated with alexithymia in SLE patients. METHODS: Fifty-three sequential SLE
      patients (ACR criteria) and 41 asthma patients were studied by means of validated
      scales for alexithymia (Toronto Alexithymia Scale), psychopathology (Brief
      Symptom Inventory, Hospital Anxiety and Depression Scale), personality dimensions
      (NEO-FFI), and quality of life (Short Form-36 Health Survey). Systemic lupus
      erythematosus patient's clinical and laboratorial evaluation was performed by
      indicators of activity (Systemic Lupus Erythematosus Disease Activity Index) of
      accumulated damage (Systemic Lupus International Collaborating Clinics/ACR Damage
      Index), length of disease, and therapy. RESULTS: An association between
      alexithymia and psychopathological symptoms, and personality and quality of life
      dimensions was found. By means of multiple regression analysis, openness and
      depression were the 2 predictors for alexithymia in SLE patients. We found a high
      prevalence rate of alexithymia in SLE patients; however, when controlling for
      depression symptoms (Hospital Anxiety and Depression Scale-Depression, <7), we
      found a lower percentage of alexithymic traits than that of the total sample of
      SLE. CONCLUSION: Alexithymia was associated with psychological distress and with
      quality of life impairment. Understanding the role of psychological factors in
      SLE patients may contribute to a more comprehensive perspective of the disease,
      its impact on patient's daily routine, and how patients adapt emotionally to a
      chronic disease.

PMID- 21193177
TI  - Patient subgroups of schizophrenia based on the Positive and Negative Syndrome
      Scale: composition and transition between acute and subsided disease states.
AB  - The present study focuses on schizophrenia patient subgroups with specific
      symptom pattern using the Positive and Negative Syndrome Scale (PANSS). In this
      report, we intend to (1) provide a more appropriate analytic method for exploring
      the subgroups based on PANSS data, (2) validate identified subgroups with
      external variables, and (3) estimate probabilities of subgroup changes between 2
      disease states. The analyzed data include 219 acute-state patients who had
      completed the PANSS within 1 week of index admission and 225 subsided-state
      patients who were living in the community and under family care. Regression
      extension of latent class analysis was performed. We found that acute
      schizophrenia can be classified into 4 subgroups--whole syndrome, whole syndrome
      without hostility, partial syndrome with negative symptoms, and partial syndrome
      with pure reality distortion--and that subsided schizophrenia can be classified
      into 3 subgroups--florid symptom, marked negative, and remitted. Patients of the
      whole syndrome, whole syndrome without hostility, partial syndrome with negative
      symptoms, and partial syndrome with pure reality distortion subgroups at the
      acute state were most likely to transit to the florid symptom (61%), florid
      symptom (48%), marked negative (42%), and remitted (56%) subgroups at the
      subsided state, respectively. Significant relationships of obtained subgroups
      with sociodemographic variables and neurocognitive variables were identified.
      These results of different subgroups will provide the background for facilitating
      current molecular, genetic, and neurobiological studies of schizophrenia.

PMID- 21193179
TI  - The Patient Health Questionnaire-9 for measuring depressive symptoms among the
      general population in Hong Kong.
AB  - OBJECTIVES: The Patient Health Questionnaire-9 (PHQ-9) assesses depressive
      symptoms by self-report, is brief, and was developed to correspond to the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria
      for major depression. This article presents information regarding its reliability
      and validity and the distribution of scores in a Chinese community sample in Hong
      Kong. METHODS: A total of 6028 participants 15 years or older were recruited
      using random household sampling. They completed the Chinese version of the PHQ-9,
      the Happiness Scale, the Chinese Health Questionnaire, and the Short-Form 12-Item
      Health Survey (SF-12). Information was also gathered on health and health service
      use. RESULTS: Exploratory factor analysis and confirmatory factor analysis
      supported a single factor with strong loadings for all 9 items. Multiple-group
      analyses demonstrated that the structure can be generalized across sex and age
      groups (ie, adolescents, adults, and individuals 65 years or older). The internal
      consistency of the PHQ-9 was 0.82. The test-retest reliability over a 2-week
      interval was 0.76. As expected, the total score of the PHQ-9 was significantly
      associated with the Chinese Health Questionnaire (r = 0.49) and the Happiness
      Scale (r = -0.41). In addition, as expected, the relationship with the physical
      component subscale of the SF-12 was significantly weaker (r = -0.27) than for the
      mental component subscale of the SF-12 (r = -0.60). Participants with higher
      scores on the PHQ-9 were more likely to report having been diagnosed with
      depression by a physician, having chronic illness, using medicine, and using
      inpatient and outpatient health services. Almost 40% of participants did not
      report any depressive symptoms (score, 0). Self-reported symptoms at a level that
      would qualify for a diagnosis of major depressive disorder were provided by 1.7%
      of the participants. CONCLUSIONS: Our data support the reliability and validity
      of the PHQ-9 in assessing depressive symptoms among the general population in
      Hong Kong. Its validity against diagnostic interview for major depressive
      disorder and its sensitivity and specificity should be determined in future
      studies.

PMID- 21193178
TI  - Negative weight-based attitudes in treatment-seeking obese monolingual Hispanic
      patients with and without binge eating disorder.
AB  - OBJECTIVE: The aims of this study were to compare weight-based attitudes in obese
      Latino adults with and without binge eating disorder (BED) and to examine whether
      these attitudes are related to indices of eating disorder psychopathology and
      psychological functioning. METHOD: Participants were a consecutive series of 79
      monolingual Spanish-speaking-only obese Latinos (65 female, 14 male)
      participating in a randomized placebo-controlled trial performed at a Hispanic
      community mental health center. Participants were categorized as meeting the
      criteria for BED (n = 40) or obese non-binge-eating controls (n = 39) based on
      diagnostic and semistructured interviews administered by fully bilingual research
      clinicians trained specifically for this study. RESULTS: Analyses revealed that
      negative attitudes toward obesity did not differ significantly between the BED
      and non-binge-eating groups nor were they correlated with the intensity of eating
      disorder psychopathology (eg, levels of weight and shape concerns). Overall, the
      levels of negative attitudes toward obesity in this Latino/Latina group are
      similar to those reported previously for samples of English-speaking primarily
      white obese persons. DISCUSSION: These findings suggest that it may be obesity
      per se-rather than eating disorder psychopathology or body image-that heightens
      vulnerability to negative weight-based attitudes.

PMID- 21193180
TI  - Does late onset depression predispose to dementia? A retrospective, case
      controlled study.
AB  - BACKGROUND: Recent research suggests that there are clinical and biologic
      characteristics typical of late onset depression (LOD). Furthermore, evidence has
      been put forward that LOD may be a prodrome of dementia. OBJECTIVE: This study
      aims to assess the association between LOD and the development of dementia.
      SETTING: The study was conducted in a tertiary care, university-affiliated mental
      health center providing services for an urban catchment population of 800,000
      subjects. METHOD: A retrospective, case-controlled study was used. RESULTS: Fifty
      one patients with LOD who developed dementia at least 1 year after diagnosis of
      LOD were defined as the index group: 18 males and 33 females, with a mean age of
      75.4 +/- 9.2 years. These were compared with 51 patients with LOD who did not
      develop dementia during a 10-year follow-up period. Dementia types were as
      follows: 73% Alzheimer disease, 24% vascular and mixed dementia, and 3% Parkinson
      dementia. Patients with LOD who developed dementia were significantly
      characterized by having longer hospitalization for their first depressive episode
      (P = .048), having a family history of dementia (P = .022), and having been
      exposed to the Holocaust as young adults (P = .013). CONCLUSIONS: Patients with a
      history of significant traumatic experience in early life and a prolonged onset
      of depression may be at particular risk of developing dementia. This issue
      requires further long-term prospective studies.

PMID- 21193181
TI  - Validity aspects of the Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition, narcissistic personality disorder construct.
AB  - BACKGROUND: The Diagnostic and Statistical Manual of Mental Disorders (DSM),
      Fourth Edition, narcissistic personality disorder (NPD) construct has been
      criticized for being too narrowly defined, for example, by focusing on overt
      grandiosity at the expense of exhibitionism and narcissistic vulnerability and
      thus covering only parts of the domain of narcissism. The purpose of this study
      was to elucidate several validity aspects of the NPD construct. METHODS: The
      material consisted of data from 2277 patients (80% of whom had a personality
      disorder [PD]) who were admitted to units connected to The Norwegian Network of
      Psychotherapeutic Day Hospitals. The Axis II diagnoses were assessed by
      Structured Clinical Interview for DSM, Fourth Edition, Axis II Personality
      Disorders. RESULTS: The frequency of NPD was very low (0.8%). Male patients were
      overrepresented both on a diagnostic level and on criteria levels. The NPD
      category was positively associated with other cluster B disorders and negatively
      associated with avoidant PD. The criteria "demands excessive admiration" and
      "fantasies of unlimited success" correlated almost as highly with the histrionic
      PD category and loaded primarily on a histrionic factor. The dominant NPD factor
      also included the antisocial criterion of "showing no regret having injured
      others." The major part of the patients' personality pathology could be
      attributed to other PD criteria. CONCLUSIONS: The results challenge the notion of
      NPD as a distinct diagnostic category. Rather, narcissism should be conceived as
      personality dimensions pertinent to the whole range of PDs. The results support
      the views put forward by Russ et al (Refining the construct of narcissistic
      personality disorder: diagnostic criteria and subtypes. Am J Psychiatry
      2008;11:1473-1481) that what clinicians conceive as narcissism consists of
      several subtypes (dimensions). Our data support the existence of a
      grandiose/malignant type and an exhibitionistic type. Unfortunately, there was no
      measure of hypersensitivity. The proposal to delete NPD as a prototype category
      in the DSM, Fifth Edition, seems well justified. However, the proposed trait
      domain of antagonism in the DSM, Fifth Edition, seems to account better for the
      grandiose/malignant dimension than the exhibitionistic/histrionic dimension.

PMID- 21193182
TI  - Factors associated with risk of suicide in patients with hemodialysis.
AB  - Suicide risk (SR) has been associated to several factors; one of them is the
      presence of psychiatric disorders. This study has the objective of investigating
      the relationship between the risk factors for suicidal behavior in patient
      bearers of chronic renal illness who are undertaking hemodialysis treatment.
      Sixty-nine undertook a short, structured diagnostic interview. The prevalence of
      some psychiatric disorders showed itself greater in the sample than that in the
      population in general. A significant positive correlation was found between SR,
      major depressive episode, and agoraphobia without panic disorder. The religiosity
      of the patient was also evaluated as an influencing factor of SR. Nonreligious
      patients had 8 times more chance to have SR compared to religious patients.
      However, the referred effect only occurred in nondepressed religious patients.
      The latter indicated that religiosity had its effect annulled in depressed
      patients. This study shows the importance of measures of intervention in mental
      health, mainly in relation to prevention and treatment of major depressive
      episode with a view to reducing SR.

PMID- 21193183
TI  - Trauma and comorbid posttraumatic stress disorder in individuals with
      schizophrenia and substance abuse.
AB  - OBJECTIVES: The aim of this study was to investigate the occurrence of trauma and
      comorbid posttraumatic stress disorder (PTSD) in dual diagnosis patients and
      whether the trauma was related to the patient's behavior or illness. METHOD: One
      hundred ten patients with schizophrenia and comorbid substance or alcohol abuse
      were assessed for PTSD using self-report and structured interview. Traumatic
      events were classified as independent or dependent upon the patient's behavior,
      illness, or symptoms. RESULTS: One hundred patients (91%) reported at least 1
      trauma (mean, 4.3). Sixty-three patients (57%) reported a traumatic event that
      met modified-criterion A for PTSD. Thirty-one patients (28%) met criteria for
      full PTSD, and 18 (16%) had a trauma directly related to their illness. Patients
      with PTSD had significantly higher scores on positive psychotic symptoms and
      depression. CONCLUSIONS: Exposures to traumatic events and comorbid PTSD are high
      but are inflated by reactions to illness-related events such as hospitalization
      and psychotic symptoms.

PMID- 21193184
TI  - Personality differences according to age and sex in a Mexican sample using the
      Temperament and Character Inventory-Revised.
AB  - OBJECTIVES: The objectives of the study were to compare personality features
      according to age and sex cohorts in a community sample of Mexico City using the
      Temperament and Character Inventory-Revised (TCI-R) and to examine the TCI-R
      psychometric properties according to age and sex parameters. METHOD: A total of
      2076 adults filled out the Spanish version of TCI-R. RESULTS: Younger subjects
      exhibited higher novelty seeking. Self-directedness and cooperativeness scores
      increased with age. Harm avoidance and self-transcendence were lower in younger
      adults when compared with older subjects. Women scored higher than men in harm
      avoidance and reward dependence. Men between 26 and 45 years old reported higher
      novelty seeking. Women older than 25 years scored higher in self-transcendence,
      and those older than 45 years exhibited higher cooperativeness scores. The
      identified TCI-R structure corresponded to the original one. Internal consistency
      of the higher-order dimensions was good in all age cohorts, in men and women, and
      in the total sample (alphas >.80). CONCLUSION: Our results give further support
      to personality specific dominant features in men and women. Differences in age
      cohorts may be explained by maturity and personal experiences acquired during
      life. The TCI-R psychometric properties and score distributions by age and sex
      cohorts may be useful for future studies with clinical samples and for cross
      cultural comparison purposes.

PMID- 21193185
TI  - Sexual dysfunction in patients with polycystic ovary syndrome: clinical and
      hormonal correlations.
AB  - OBJECTIVE: The aim of this study was to investigate the sexual function of
      patients with polycystic ovary syndrome (PCOS), including the clinical and
      hormonal characteristics potentially related to sexual dysfunction, in an
      endocrinology and gynecology ambulatory. METHODOLOGY: Women in ambulatory
      accompaniment for PCOS (N = 88) were sequentially evaluated by means of the
      Arizona Sexual Experience Scale (ASEX) and the application of structured
      diagnostic interview Mini International Neuropsychiatric Interview (version 4.4)
      for the identification of mood disorders. The clinical and laboratorial
      parameters were examined using the patient's medical records. RESULTS: The
      incidence of sexual dysfunction was verified (13.3%), and it was observed that
      the average (SD) ASEX score of 14.4 (3.7) was comparable with that of the
      population with no medical problems. There is a negative correlation between the
      scores of ASEX and the levels of total testosterone (-0.360), luteinizing hormone
      (-0.397), and dehydroepiandrosterone sulfate (-0.723). CONCLUSION: The main
      factors of preservation of the sexual function in our sample were identified as
      the low average age of the patients in treatment and the hyperandrogenism
      habitually found as a consequence of the physiopathology of PCOS.

PMID- 21193186
TI  - [Vascular risk factors in HIV-infected patients in a penitentiary center].
AB  - OBJECTIVE: There is little data regarding vascular risk factors (VRF) in HIV
      infected inmates. In this study, we have studied the prevalence of VRF in HIV
      infected patients, analyzing the differences with a non-infected population.
      PATIENTS AND METHOD: HIV-infected inmates (n=80) and two non-HIV controls
      selected for each patient and matched for age and sex (n=160) were included in a
      descriptive cross-sectional study. We analyzed the VRF, and risk was assessed
      according to the SCORE, Framingham and REGICOR functions. RESULTS: In the studied
      population (mean age: 38.1 years; 92.5% men), HIV-infected patients had a
      significantly higher prevalence of cigarette smoking (97.5 vs 78.8%), diabetes
      (8.8 vs 1.3%), serum triglyceride s>150 mg/dl (43.8 vs 26.3%), low HDL
      cholesterol levels (61.3 vs 40.6%), HCV infection (87.5 vs 22.5%), and cocaine
      consumption (77.5 vs 39.4%). The non-infected group had significantly higher
      prevalence of total cholesterol>200mg/dl and/or LDL-cholesterol >130 mg/dl (45.6
      vs 28.8%), obesity (14.4 vs 2.5%), sedentary lifestyle (67.5 vs 42.5%) and
      increased waist circumference (14.4 vs 3.8%). All the evaluated inmates were
      considered to be at a low risk by SCORE and REGICOR, and 1.3% to be at a high
      risk by Framingham in both groups. CONCLUSION: The prevalence of VRF in HIV
      infected patients of the studied prison was much higher to that of the HIV
      negative subjects. However, the estimation of the cardiovascular risk was low.

PMID- 21193188
TI  - Serum paraoxonase 1 activity, asymmetric dimethylarginine levels, and brachial
      artery flow-mediated dilatation in women with polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate endothelial function via serum asymmetric dimethylarginine
      (ADMA) levels, paraoxonase 1 (PON1) activity, and brachial artery flow-mediated
      dilatation (FMD) in women with polycystic ovary syndrome (PCOS). DESIGN:
      Prospective case-control study. SETTING: University hospital. PATIENT(S): Thirty
      patients with PCOS with a mean age of 24.33 +/- 4.50 years and 30 healthy
      controls matched for body mass index (BMI) and age. INTERVENTION(S): Endothelial
      function was assessed biochemically with serum ADMA levels and serum PON1
      activity and functionally with brachial artery FMD by ultrasonography. MAIN
      OUTCOME MEASURE(S): Serum ADMA levels, serum PON1 activity, brachial artery FMD,
      hormonal and biochemical parameters. RESULT(S): Patients with PCOS had higher
      levels of free testosterone and insulin, and higher waist-hip ratio and Ferriman
      Gallwey scores when compared with the controls. Fasting glucose and homeostasis
      model assessment of insulin resistance were not different between the groups.
      There was no statistically significant difference in ADMA levels between two
      groups. Serum PON1 activity and brachial artery FMD were statistically
      significantly lower in women with PCOS. There was negative correlation between
      ADMA and PON1 in patients with PCOS. CONCLUSION(S): Serum PON1 activity and
      brachial artery FMD, as markers of endothelial dysfunction and cardiovascular
      risk, were statistically significantly lower in women with PCOS compared with
      healthy controls matched for age and BMI. Endothelial dysfunction may be seen at
      earlier ages in patients with PCOS.

PMID- 21193189
TI  - Finasteride-associated male infertility.
AB  - OBJECTIVE: To describe a male patient with finasteride-associated infertility.
      DESIGN: Case report. SETTING: Tertiary-care clinic for male infertility.
      PATIENT(S): A patient with azoospermia who had been taking finasteride (1-mg
      dose) for 1 year for androgenic alopecia. He had been diagnosed with oligospermia
      5 years before. INTERVENTION(S): Discontinuation of finasteride. MAIN OUTCOME
      MEASURE(S): Improvement of semen parameters. RESULT(S): After cessation of
      finasteride, the patient's semen volume increased immediately, and sperm
      concentration was up to more than 10 * 10(6)/mL 16 weeks after stopping
      finasteride. He is now trying to achieve pregnancy by intrauterine insemination.
      CONCLUSION(S): Cessation of finasteride improved spermatogenesis and allowed the
      couple to attempt less-invasive fertility therapy. In this case, the patient had
      impaired spermatogenesis before he started the drug. In such patients, the drug
      may further decrease spermatogenesis. We suggest that drug cessation could be
      taken into consideration for infertile male patients with impaired semen
      parameters who are taking finasteride at a 1-mg dose.

PMID- 21193187
TI  - The effects of metformin with lifestyle therapy in polycystic ovary syndrome: a
      randomized double-blind study.
AB  - OBJECTIVE: To determine if the combination of lifestyle (caloric restriction and
      exercise) and metformin (MET) would be superior to lifestyle and placebo (PBO) in
      improving the polycystic ovary syndrome (PCOS) phenotype. DESIGN: Double-blind
      randomized 6-month trial of MET versus PBO. SETTING: Two academic medical
      centers. PATIENT(S): One hundred fourteen subjects with PCOS were randomized to
      MET (N = 55) or PBO (N = 59). INTERVENTION(S): Subjects collected urine daily for
      ovulation monitoring, had monthly monitoring of hormones and weight and
      determination of body composition by dual-energy x-ray absorptiometry, glucose
      tolerance, and were evaluated for quality of life at baseline and completion.
      MAIN OUTCOME MEASURE(S): Ovulation rates and testosterone levels. RESULT(S):
      Dropout rates were high. There was no significant difference in ovulation rates.
      Testosterone levels were significantly lower compared with baseline in the MET
      group at 3 mos but not at 6 mos. There were no differences in weight loss between
      groups, but MET showed a significant decline at 6 months compared with baseline (
      3.4 kg, 95% confidence interval -5.3 to -1.5 kg). We noted divergent effects of
      MET versus PBO on oral glucose tolerance test indices of insulin sensitivity
      (increased) and secretion (worsened). Total bone mineral density increased
      significantly in MET. There were no differences in quality of life measures
      between the groups. The MET group had increased diarrhea and headache, but fewer
      bladder infections and musculoskeletal complaints. CONCLUSION(S): The addition of
      metformin to lifestyle therapy produced little reproductive or glycemic benefit
      in women with PCOS, although our study had limited power owing to a high dropout
      rate. It is not possible at baseline to identify women likely to drop out.

PMID- 21193190
TI  - Effect of levothyroxine treatment on in vitro fertilization and pregnancy outcome
      in infertile women with subclinical hypothyroidism undergoing in vitro
      fertilization/intracytoplasmic sperm injection.
AB  - OBJECTIVE: To investigate whether levothyroxine (LT4) treatment has beneficial
      effects on IVF results and pregnancy outcome in infertile patients with
      subclinical hypothyroidism undergoing IVF/intracytoplasmic sperm injection
      (ICSI). DESIGN: Prospective, randomized trial. SETTING: University-affiliated
      infertility clinic. PATIENT(S): A total of 64 infertile patients with subclinical
      hypothyroidism, defined as an elevated serum TSH level associated with a normal
      free T4 level and without frank symptoms of hypothyroidism. INTERVENTION(S):
      Patients were randomized into an LT4 treatment group or control group. For the
      LT4 treatment group, 50 MUg LT4 was administered from the first day of controlled
      ovarian stimulation for IVF/ICSI. MAIN OUTCOME MEASURE(S): Results of IVF and
      pregnancy outcome. RESULT(S): There were no differences in patient
      characteristics between the two groups. Total dose and days of recombinant human
      FSH used for controlled ovarian stimulation were also similar. The number of
      grade I or II embryos was significantly higher in the LT4 treatment group than in
      the control group. There was no significant difference in the clinical pregnancy
      rate per cycle between the two groups. However, the miscarriage rate was
      significantly lower in the LT4 treatment group than in the control group. Embryo
      implantation rate and live birth rate were significantly higher in the LT4
      treatment group. In the control group, both thyroid peroxidase antibody and
      thyroglobulin antibody levels were significantly higher in the miscarried
      subgroup than in the delivered subgroup. CONCLUSION(S): LT4 treatment can improve
      embryo quality and pregnancy outcome in subclinical hypothyroid women undergoing
      IVF/ICSI.

PMID- 21193191
TI  - A prospective, controlled, randomized, multicenter, exploratory pilot study
      evaluating the safety and potential trends in efficacy of Adhexil.
AB  - OBJECTIVE: To present a multicenter, reviewer-blinded pilot study evaluating the
      safety and trends of efficacy of Adhexil, a novel product using fibrin sealant.
      DESIGN: Randomized, reviewer-blinded assessment of postoperative adhesion
      development in women with bilateral ovarian disease. SETTING: Gynecologic
      clinics. PATIENT(S): Women undergoing gynecologic surgery. INTERVENTION(S):
      Patients were assessed for incidence, extent, and severity of ovarian adhesions
      at the first-look laparoscopy (1LL), followed by standard surgical procedure.
      Ovaries were randomized for application of Adhexil or untreated. A second-look
      laparoscopy (2LL) was performed to assess postoperative adhesions. MAIN OUTCOME
      MEASURE(S): Safety and efficacy of Adhexil. RESULT(S): A trend toward improvement
      in adhesion incidence was found in the treated ovaries, with 50% (8/16) of
      adhesion free ovaries in the Adhexil group, versus 31% (5/16) of control ovaries.
      Similarly, the improvement in the mean American Fertility Society (AFS) score in
      the Adhexil-treated group from 1LL (6.4 +/- 6.8) to 2LL (4.6 +/- 6.9) was
      observed, whereas worsening of adhesions was observed on the control side from
      1LL (5.6 +/- 5.1) to 2LL (7.1 +/- 6.9). No adverse events or serious adverse
      events considered related to the study product were reported. CONCLUSION(S): A
      clear trend of efficacy for Adhexil reducing the incidence, severity, and extend
      of adhesions in laparoscopic gynecology surgery, despite the small sample size.
      The use of Adhexil appears safe. Further exploration of its safety and efficacy
      in preventing/reducing postsurgical adhesions is warranted.

PMID- 21193193
TI  - Performances improvements and torque ripple minimization for VSI fed induction
      machine with direct control torque.
AB  - This paper describes a torque ripple reduction technique with constant switching
      frequency for direct torque control (DTC) of an induction motor (IM). This method
      enables a minimum torque ripple control. In order to obtain a constant switching
      frequency and hence a torque ripple reduction, we propose a control technique for
      IM. It consists of controlling directly the electromagnetic torque by using a
      modulated hysteresis controller. The design methodology is based on space vector
      modulation (SVM) of electrical machines with digital vector control. MATLAB
      simulations supported with experimental study are used. The simulation and
      experimental results of this proposed algorithm show an adequate dynamic to IM;
      however, the research can be extended to include synchronous motors as well. The
      implementation of the proposed algorithm is described. It doesn't require any PI
      controller in the torque control loop. The hardware inverter is controlled
      digitally using a Texas Instruments TMS320F240 digital signal processor (DSP)
      with composed C codes for generating the required references. The results
      obtained from simulation and experiments confirmed the feasibility of the
      proposed strategy compared to the conventional one.

PMID- 21193192
TI  - Antral follicle count provides additive information to hormone measures for
      determining ovarian function in breast cancer survivors.
AB  - In breast cancer survivors, antral follicle count appears to provide data on
      ovarian function that are independent of antimullerian hormone, FSH, and inhibin
      B. Therefore, ultrasound appears to be a tool that may not only corroborate, but
      also add to the accuracy of hormone measures for determining ovarian function in
      breast cancer survivors.

PMID- 21193194
TI  - Adaptive filter design based on the LMS algorithm for delay elimination in TCR/FC
      compensators.
AB  - Thyristor controlled reactor with fixed capacitor (TCR/FC) compensators have the
      capability of compensating reactive power and improving power quality phenomena.
      Delay in the response of such compensators degrades their performance. In this
      paper, a new method based on adaptive filters (AF) is proposed in order to
      eliminate delay and increase the response of the TCR compensator. The algorithm
      designed for the adaptive filters is performed based on the least mean square
      (LMS) algorithm. In this design, instead of fixed capacitors, band-pass LC
      filters are used. To evaluate the filter, a TCR/FC compensator was used for
      nonlinear and time varying loads of electric arc furnaces (EAFs). These loads
      caused occurrence of power quality phenomena in the supplying system, such as
      voltage fluctuation and flicker, odd and even harmonics and unbalancing in
      voltage and current. The above design was implemented in a realistic system model
      of a steel complex. The simulation results show that applying the proposed
      control in the TCR/FC compensator efficiently eliminated delay in the response
      and improved the performance of the compensator in the power system.

PMID- 21193195
TI  - A new combined method in active filter design for power quality improvement in
      power systems.
AB  - The voltage & current harmonics produced by nonlinear loads in power systems
      cause a reduction in power quality. In order to improve the power quality, active
      power filters (APFs) can be used. In this paper, a new control system for
      designing active filters despite nonlinear loads of electric arc furnaces (EAFs)
      is presented. The system is composed of three main parts: computation of
      reference currents, regulation of DC capacitor voltage, and production of firing
      pulses. In the first part, the active filter control system is presented based on
      the combination of the synchronous detection method and instantaneous power
      theory. In the second part, the DC capacitor voltage regulator is applied,
      producing a reference current and a proper voltage regulator is developed. For
      the third part of the control system, we use a PI controller to provide some
      conditions that follow the reference current in a complete cycle, and generate
      firing pulses by the hysteresis method. The proposed control system not only
      reduces the voltage and current harmonics in power systems but can also improve
      the power quality indices. The above design was implemented in the EAF system of
      the Mobarakeh steel complex (Isfahan, Iran). The simulation results show the
      effectiveness of the APFs in improving the power quality indices.

PMID- 21193196
TI  - Detection of coronary atherosclerotic plaques with superficial proteoglycans and
      foam cells using real-time intrinsic fluorescence spectroscopy.
AB  - OBJECTIVES: The protein components of low-density lipoprotein (LDL), oxidized LDL
      and proteoglycans such as versican contain tryptophan, an amino acid with
      characteristic fluorescence features at 308 nm excitation wavelength. We
      hypothesize that intrinsic fluorescence spectroscopy at 308 nm excitation
      wavelength IFS308, a method suitable for clinical use, can identify coronary
      artery lesions with superficial foam cells (SFCs) and/or proteoglycans. METHODS:
      We subjected 119 human coronary artery specimens to in vitro fluorescence and
      reflectance spectroscopy. We used 5 basis spectra to model IFS308, and extracted
      their contributions to each individual IFS308 spectrum. A diagnostic algorithm
      using the contributions of Total Tryptophan and fibrous cap to IFS308 was built
      to identify specimens with SFCs and/or proteoglycans in their top 50 MUm.
      RESULTS: We detected SFCs and/or proteoglycans, such as versican or the
      glycosaminoglycan hyaluronan, in 24 fibrous cap atheromas or pathologic intimal
      thickening (PIT) lesions. An algorithm using the contributions of Total
      Tryptophan and fibrous cap to IFS308 was able to identify these segments with 92%
      sensitivity and 80% specificity. CONCLUSION: We were able to establish a set of
      characteristic LDL, oxidized LDL, versican and hyaluronan fluorescence spectra,
      ready to be used for real-time diagnosis. The IFS(308) technique detects SFCs
      and/or proteoglycans in fibrous cap atheromas and PIT lesions. SFCs and
      proteoglycans are histological markers of vulnerable plaques, and this study is a
      step further in developing an invasive clinical tool to detect the vulnerable
      atherosclerotic plaque.

PMID- 21193197
TI  - Eicosapentaenoic acid reduces warfarin-induced arterial calcification in rats.
AB  - BACKGROUND: Eicosapentaenoic acid (EPA), a major n-3 polyunsaturated fatty acid,
      is reported to have various protective effects for cardiovascular disease.
      However, few studies have focused on the influence of EPA on vascular
      calcification. METHODS AND RESULTS: Arterial medial calcification (AMC) was
      induced by administering warfarin (3 mg/g food) and vitamin K1 (1.5 mg/g food)
      for 2 weeks in Sprague-Dawley rats (control group), and EPA (1 g/kg/day) was
      administered for 2 weeks simultaneously with warfarin and vitamin K1 (EPA group)
      or after initiation of AMC (late EPA group). EPA showed a marked reduction of
      medial calcification in the EPA group, and showed a similar effect in the late
      EPA group. Immunohistochemical and RT-PCR analyses showed that EPA lowered the
      expression of osteogenetic markers, such as osteopontin, alkaline phosphatase and
      core binding factor-alpha1 in the aorta. Significant migration of macrophages
      with expression of matrix-metalloproteinase (MMP)-2 or MMP-9 was observed in the
      aortic adventitia around calcification. EPA also reduced macrophage infiltration,
      MMP-9 expression as well as gene expression of monocyte chemotactic protein (MCP)
      1. CONCLUSIONS: These observations indicate that EPA attenuates arterial medial
      calcification through an effect associated with the suppression of MMP-9 activity
      and inhibition of macrophage infiltration as well as osteogenic protein
      expression in warfarin-induced rat models.

PMID- 21193198
TI  - Predictive role of polymorphisms in interleukin-5 receptor alpha-subunit,
      lipoprotein lipase, integrin A2 and nitric oxide synthase genes on ischemic
      stroke in type 2 diabetes--an 8-year prospective cohort analysis of 1327 Chinese
      patients.
AB  - OBJECTIVE: Ischemic stroke is prevalent in type 2 diabetes and may be due to
      metabolic, vascular and inflammatory factors. Genetic variants implicated in
      these pathways may have joint effects on stroke risk. In this proof-of-concept
      study, we examined gene-gene interactions on risk of incident ischemic stroke in
      an 8-year prospective cohort of Chinese type 2 diabetic patients. METHODS:
      Seventy-seven single nucleotide polymorphisms (SNPs) of 53 candidate genes for
      cardiovascular disease and inflammation were genotyped in 1327 patients with no
      past history of ischemic stroke. The association of SNPs with stroke was tested
      using Cox proportional hazard regression analysis. Permutation procedure was
      performed to control for multiple statistical comparisons. RESULTS: Genetic
      variants including A/A of IL5RA (interleukin-5 alpha subunit) -5091G>A, X/X of
      LPL (lipoprotein lipase) S447X, A/A of ITGA2 (integrin A2) G873A and T/T or G/T
      of NOS3 (endothelial nitric oxide synthase) G894T showed significant correlations
      with incident ischemic stroke. The hazard ratios (HR) increased with number of
      genetic risk factors reaching an adjusted HR (confidence interval) of 3.68 (1.78
      7.62, P=4.4*10(-4)) in those with >=2 genetic risk factors compared to those
      without. CONCLUSION: Polymorphisms in IL5RA, LPL, ITGA2 and NOS3 genes were
      independently associated with ischemic stroke in Chinese diabetic population.

PMID- 21193199
TI  - Improvement of lipoprotein separation with a guard channel prior to asymmetrical
      flow field-flow fractionation using fluorescence detection.
AB  - In this article, a simple experimental approach to improve lipoprotein separation
      and detection in flow field-flow fractionation (FlFFF) is detailed. Lipoproteins
      are globular particles composed of lipids and proteins in blood serum and their
      roles include transferring fats and cholesterols through blood vessels throughout
      the body. Especially, presence of small, dense low-density lipoproteins (LDL) is
      associated with cardiovascular risk. Two experimental approaches were explored in
      this study: an increase in the reproducibility of LDL particle separation by
      implementing a guard channel prior to an asymmetrical FlFFF (AFlFFF) channel in
      order to deplete small molecular weight serum proteins and reducing the required
      injection volume of a serum sample by implementing fluorescence detection. The
      guard channel was made of a simple hollow fiber module so that the serum sample
      can be washed with the help of radial flow prior to injection into the AFlFFF
      channel. The channel was tested with protein standards and serum samples to
      ensure precision of the retention time and the protein recovery rate. A
      fluorescent phospholipid dye was utilized to label lipoprotein particles before
      separation for fluorescence detection, which resulted in a reduction of the
      required injection volume of serum.

PMID- 21193200
TI  - Hydration of methane intercalated in Na-smectites with distinct layer charge:
      insights from molecular simulations.
AB  - Molecular dynamic simulations have been carried out to investigate the behavior
      of methane hydration in Na-smectite interlayers with different layer-charge
      distributions and water contents under certain pressure-temperature (P-T)
      conditions, which is analogous to the methane hydrate-bearing marine sediments.
      It was found that sufficient interlayer water is necessary for coordinating with
      methane and forming hydrate-like structures. Methane molecules are solvated by
      nearly 12-13 water molecules and coordinated with six oxygen atoms from the clay
      surface in the interlayer of nontronite as well as in montmorillonite. The
      mobility of the interlayer water of smectite, which is determined by the layer
      charge amount and distribution of smectite, also influences the stability of
      hydrate methane complexes. The tetrahedral negative charge site is closer to the
      surface than the octahedral charge site and is more effective in confining water
      than methane water molecules.

PMID- 21193201
TI  - Partition coefficients of nonionic surfactants in water/n-alkane systems.
AB  - In water/oil systems, surfactants partition between the water phase and the oil
      phase according to their solubility in both phases. The ratio between the
      concentration of the surfactant in the oil phase and in the water phase at
      equilibrium is known as the partition or distribution coefficient (K(p)). The
      partition coefficient (K(p)) is an important fundamental parameter essential to
      understanding and controlling phenomena in water-oil-surfactant systems under
      both equilibrium and non-equilibrium conditions. In the present work we report on
      the partitioning of three different classes of nonionic surfactants in the pre
      cmc regime, namely polyoxyethylene alkyl ethers (C(i)E(j)), alkyl dimethyl
      phosphine oxides (C(n)DMPO) and alkyl glycosides (beta-C(n)G(m)) between water
      and different n-alkanes. We focus on the influence of the surfactant's molecular
      structure (alkyl chain length, head group size and type), and oil chain length on
      K(p) to derive systematic structure-property relationships. Moreover, we discuss
      the influence of the surfactant purity on partition coefficients of technical
      grade alkyl glycosides and polyoxyethylene alkyl ethers, respectively.

PMID- 21193202
TI  - Lipid membranes supported on optically transparent nanosilicas: synthesis and
      application in characterization of protein-membrane interactions.
AB  - We describe methods of preparation of lipid membranes supported on optically
      transparent nanosilicas (20 and 30 nm diameter) and an initial application of
      these materials to characterize membrane-protein binding using conventional
      circular dichroism and fluorescence spectroscopy.

PMID- 21193203
TI  - Effect of repulsive interactions on the rate of doublet formation of colloidal
      nanoparticles in the presence of convective transport.
AB  - In this work, we have performed a systematic investigation of the effect of
      electrostatic repulsive interactions on the aggregation rate of colloidal
      nanoparticles to from doublets in the presence of a convective transport
      mechanism. The aggregation rate has been computed by solving numerically the
      Fuchs-Smoluchowski diffusion-convection equation. Two convective transport
      mechanisms have been considered: extensional flow field and gravity-induced
      relative sedimentation. A broad range of conditions commonly encountered in the
      applications of colloidal dispersions has been analyzed. The relative importance
      of convective to diffusive contributions has been quantified by using the Peclet
      number Pe. The simulation results indicate that, in the presence of repulsive
      interactions, the evolution of the aggregation rate as a function of Pe can
      always be divided into three distinct regimes, no matter which convective
      mechanism is considered. At low Pe values the rate of aggregation is independent
      of convection and is dominated by repulsive interactions. At high Pe values, the
      rate of aggregation is dominated by convection, and independent of repulsive
      interactions. At intermediate Pe values, a sharp transition between these two
      regimes occurs. During this transition, which occurs usually over a 10-100-fold
      increase in Pe values, the aggregation rate can change by several orders of
      magnitude. The interval of Pe values where this transition occurs depends upon
      the nature of the convective transport mechanism, as well as on the height and
      characteristic lengthscale of the repulsive barrier. A simplified model has been
      proposed that is capable of quantitatively accounting for the simulations
      results. The obtained results reveal unexpected features of the effect of ionic
      strength and particle size on the stability of colloidal suspensions under shear
      or sedimentation, which have relevant consequences in industrial applications.

PMID- 21193204
TI  - Cross-sectional and longitudinal assessment of aortic root dilation and valvular
      anomalies in hypermobile and classic Ehlers-Danlos syndrome.
AB  - OBJECTIVES: To delineate the prevalence of cardiac findings in hypermobile and
      classic Ehlers-Danlos syndrome and provide longitudinal analysis of aortic root
      growth. STUDY DESIGN: A retrospective chart review was conducted, and data were
      analyzed for cross-sectional prevalence of aortic dilation and valvular
      anomalies. The clinical implications of aortic root growth were determined by
      assessment of progression of aortic root measurements over time and clinical
      symptoms. RESULTS: Patients whose first echocardiogram was obtained in late
      childhood or adulthood were less likely to have aortic dilation (P < .002) than
      those whose first echocardiogram was obtained in early childhood. Longitudinally,
      seven individuals had dilated aortas before age 14, and only one individual
      continued to show dilation after age 14 (P = .0143). No patient with a normal
      aortic root in childhood had development of dilation in adulthood. Fifteen of the
      252 patients (6.0%) had mitral valve prolapse (MVP), although only one patient
      (0.4%) had MVP that was mild to moderate. CONCLUSIONS: Although aortic root size
      and MVP are increased in patients with these types of Ehlers-Danlos syndrome,
      they tend to be of little clinical consequence. Echocardiography may still be
      warranted as part of cardiovascular assessment, but decreased frequency of
      screening is recommended especially in symptom-free adults.

PMID- 21193205
TI  - Increase in invasive Streptococcus pneumoniae infections in children with sickle
      cell disease since pneumococcal conjugate vaccine licensure.
AB  - Invasive pneumococcal disease (IPD) in children with sickle cell disease has
      decreased with prophylactic penicillin, pneumococcal polysaccharide vaccine, and
      pneumococcal protein-conjugate vaccine usage. We report 10 IPD cases since
      pneumococcal protein-conjugate vaccine licensure, including a recent surge of non
      vaccine serotypes. IPD continues to be a serious risk in sickle cell disease.

PMID- 21193207
TI  - [Small fiber sensory neuropathies: contribution of laser evoked potentials].
AB  - Standard neurophysiological techniques evaluate exclusively large myelinated
      fibers, but are not useful to explore sensory small fibers. Quantitative sensory
      tests have been developed to explore the thermal nociceptive function but this
      exploration is only subjective. Laser evoked potentials (LEPs) represent a
      noninvasive and objective test to explore thermal and nociceptive pathways. The
      clinical interest of LEPs have been assessed recently in the diagnosis of small
      fibers sensory neuropathies. In routine, the determination of detection and
      nociceptive thresholds, the analysis of N2P2 latencies and amplitudes enable
      demonstration of a dysfunction of A delta nerve fibers, to quantify these lesions
      and to determine whether the neuropathies are length-dependent or not. The LEP
      amplitude is negatively correlated to deafferentation. The interest of LEPs
      remained to be studied compared to skin biopsy.

PMID- 21193206
TI  - A clinically applicable porcine model of septic and ischemia/reperfusion-induced
      shock and multiple organ injury.
AB  - BACKGROUND: Although many sepsis treatments have shown efficacy in acute animal
      models, at present only activated protein C is effective in humans. The likely
      reason for this discrepancy is that most of the animal models used for
      preclinical testing do not accurately replicate the complex pathogenesis of human
      sepsis. Our objective in this study was to develop a clinically applicable model
      of severe sepsis and gut ischemia/reperfusion (I/R) that would cause multiple
      organ injury over a period of 48 h. MATERIALS AND METHODS: Anesthetized,
      instrumented, and ventilated pigs were subjected to a "two-hit" injury by
      placement of a fecal clot through a laparotomy and by clamping the superior
      mesenteric artery (SMA) for 30 min. The animals were monitored for 48 h. Wide
      spectrum antibiotics and intravenous fluids were given to maintain hemodynamic
      status. FiO(2) was increased in response to oxygen desaturation. Twelve hours
      following injury, a drain was placed in the laparotomy wound. Extensive
      hemodynamic, lung, kidney, liver, and renal function measurements and serial
      measurements of arterial and mixed venous blood gases were made. Bladder pressure
      was measured as a surrogate for intra-peritoneal pressure to identify the
      development of the abdominal compartment syndrome (ACS). Plasma and peritoneal
      ascites cytokine concentration were measured at regular intervals. Tissues were
      harvested and fixed at necropsy for detailed morphometric analysis. RESULTS:
      Polymicrobial sepsis developed in all animals. There was a progressive
      deterioration of organ function over the 48 h. The lung, kidney, liver, and
      intestine all demonstrated clinical and histopathologic injury. Acute lung injury
      (ALI) and ACS developed by consensus definitions. Increases in multiple cytokines
      in serum and peritoneal fluid paralleled the dysfunction found in major organs.
      CONCLUSION: This animal model of Sepsis+I/R replicates the systemic inflammation
      and dysfunction of the major organ systems that is typically seen in human sepsis
      and trauma patients. The model should be useful in deciphering the complex
      pathophysiology of septic shock as it transitions to end-organ injury thus
      allowing sophisticated preclinical studies on potential treatments.

PMID- 21193208
TI  - Krox20 inactivation in the PNS leads to CNS/PNS boundary transgression by central
      glia.
AB  - CNS/PNS interfaces constitute cell boundaries, since they delimit territories
      with different neuronal and glial contents. Despite their potential interest in
      regenerative medicine, the mechanisms restricting oligodendrocytes and astrocytes
      to the CNS, and Schwann cells to the PNS in mammals are not known. To investigate
      the involvement of peripheral glia and myelin in the maintenance of the CNS/PNS
      boundary, we have first made use of different mouse mutants. We show that
      inactivation of Krox20/Egr2, a master regulatory gene for myelination in Schwann
      cells, results in transgression of the CNS/PNS boundary by astrocytes and
      oligodendrocytes and in myelination of nerve root axons by oligodendrocytes. In
      contrast, such migration does not occur with the Trembler(J) mutation, which
      prevents PNS myelination without affecting Krox20 expression. Altogether these
      data suggest that maintenance of the CNS/PNS boundary requires a new Krox20
      function separable from myelination control. Finally, we have analyzed a human
      patient affected by a congenital amyelinating neuropathy, associated with the
      absence of the KROX20 protein in Schwann cells. In this case, the nerve roots
      were also invaded by oligodendrocytes and astrocytes. This indicates that
      transgression of the CNS/PNS boundary by central glia can occur in pathological
      situations in humans and suggests that the underlying mechanisms are common with
      the mouse.

PMID- 21193209
TI  - Macrophage migration inhibitory factor is a potential inducer of endothelial
      progenitor cell mobilization after flap operation.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) promote angiogenesis and play an
      important role in tissue revascularization and wound healing. Yet, the exact
      stimuli and mechanisms for the mobilization remain understood poorly. Macrophage
      migration inhibitory factor (MIF), which is a structurally unique pleiotropic
      cytokine, has been suggested to play a role in EPC recruitment and thus was a
      target of this study. METHODS: This study included 20 patients who underwent flap
      operation. Subjects were divided into 3 groups according to the pattern of flap
      applied. The number of circulating EPCs and serum levels of MIF or CXCL12 were
      determined at different time intervals. In vitro chemotaxis experiments using
      Transwell devices were carried out to test whether MIF promotes the chemotactic
      migration of EPCs. To underscore functionally the chemotactic potential of MIF
      toward EPCs in flap patients, the chemotactic effects of serum samples from all
      groups were also examined in the presence and absence of monoclonal anti
      macrophage migration inhibitory factor and anti-CXCL12 antibodies on EPC
      recruitment using in vitro migration chambers. RESULTS: In flap patients, the
      number of circulating EPCs and serum levels of MIF but not CXCL12 serum levels
      were increased markedly compared with preoperative levels at day 1 after
      operation, especially in the group of free microvascular flaps. Serum levels of
      CXCL12 in the flap patients were increased only significantly compared with the
      healthy control group. An analysis between EPCs and MIF revealed a significant
      correlation, whereas no correlation was observed for CXCL12. MIF exerted a dose
      dependent, prochemotactic effect on isolated human EPCs, and serum samples from
      all flap patients promoted EPC migration. Importantly, this effect was blocked
      partially by anti-macrophage migration inhibitory factor and to a weaker extent
      by anti-CXCL12 antibodies. CONCLUSION: We conclude that MIF plays an important
      role in the mobilization of EPCs, which is dependent on the degree of ischemia.
      Enhancement by MIF of chemotactic EPCs migration in vitro underpins its proposed
      in vivo function.

PMID- 21193210
TI  - Modulation of matrix metalloproteinase activity in human thyroid cancer cell
      lines using demethylating agents and histone deacetylase inhibitors.
AB  - BACKGROUND: The purpose of this study was to investigate the effects of treating
      human thyroid cancer cell lines with demethylating agents and histone deacetylase
      (HDAC) inhibitors to see if they would downregulate expression and activity of
      the matrix metalloproteinases (MMP)-2 and MMP-9, resulting in inhibition of
      growth and invasion. METHODS: A total of 1 papillary cancer cell line (TPC-1) and
      3 follicular thyroid cancer cell lines (FTC-133, FTC-236, and FTC-238) were
      treated with the demethylating agent 5-azacytidine (5-AZC) and the HDAC
      inhibitors trichostatin A (TSA) and valproic acid (VA). The activity of MMP
      proteins was determined using gelatin zymography, and commercially available
      assays were used to quantify growth inhibition and thyroid cancer cell invasion.
      RESULTS: Treatment with TSA and VA resulted in decreased protein activity of MMP
      2 and MMP-9 in all cell lines in a dose-dependent manner after 48 hours of
      treatment compared with untreated controls. In addition, 5-, TSA, and VA caused
      inhibition of growth in the range of 25-80% for all cell lines at 24, 48, and 72
      hours. VA and TSA significantly decreased cell invasion in the FTC-133 and TPC-1
      cell lines. CONCLUSION: The HDAC inhibitors TSA and VA decreased the protein
      activity of MMP-2 and MMP-9 and, in combination with the demethylating agent 5
      AZC, inhibited cellular growth in human papillary and follicular thyroid cancer
      cell lines. These results elucidate our understanding of the pathways affected by
      the demethylating agents and HDAC inhibitors, and provide further evidence that
      MMPs are a potentially useful target for molecular therapies in patients with
      aggressive or refractory thyroid cancers.

PMID- 21193211
TI  - Sequences in the U3 region of human immunodeficiency virus 1 improve efficiency
      of minus strand transfer in infected cells.
AB  - A tRNA gene-like sequence has been identified near the 3' end of HIV-1. Two
      segments of this sequence (motif 9 and segment 1) promoted minus strand transfer
      in vitro. The segments are complementary to the tRNA(3)(Lys) primer, and
      apparently act by binding the tRNA, thereby bringing the 3' and 5' ends of viral
      RNA into proximity for strand transfer. In this report, we used full-length HIV-1
      to demonstrate biological relevance of these segments. We constructed HIV-1
      genomes capable of single cycle infection and altered in one or both of two
      segments. We devised a real time PCR method for quantifying the amount of (
      )ssDNA that completes transfer. Results showed that depending on the mutation the
      efficiency of transfer decreased from 9% to 26%. Alteration of segment 1 had the
      greatest effect. Alteration of motif 9 or both sequences also caused a reduction,
      but smaller than alteration of segment 1 alone.

PMID- 21193212
TI  - Recruitment of DNA replication and damage response proteins to viral replication
      centers during infection with NS2 mutants of Minute Virus of Mice (MVM).
AB  - MVM NS2 is essential for viral DNA amplification, but its mechanism of action is
      unknown. A classification scheme for autonomous parvovirus-associated replication
      (APAR) center development, based on NS1 distribution, was used to characterize
      abnormal APAR body maturation in NS2null mutant infections, and their
      organization examined for defects in host protein recruitment. Since acquisition
      of known replication factors appeared normal, we looked for differences in
      invoked DNA damage responses. We observed widespread association of H2AX/MDC1
      damage response foci with viral replication centers, and sequestration and
      complex hyperphosphorylation of RPA(32), which occurred in wildtype and mutant
      infections. Quantifying these responses by western transfer indicated that both
      wildtype and NS2 mutant MVM elicited ATM activation, while phosphorylation of
      ATR, already basally activated in asynchronous A9 cells, was downregulated. We
      conclude that MVM infection invokes multiple damage responses that influence the
      APAR environment, but that NS2 does not modify the recruitment of cellular
      proteins.

PMID- 21193213
TI  - Surfactant-coated aluminum hydroxide for the rapid removal and biodegradation of
      hydrophobic organic pollutants in water.
AB  - The removal of hydrophobic organic pollutants in water to surfactant-coated
      aluminum hydroxide [surfactant-Al(OH)(3)] was investigated. Anionic surfactants
      such as sodium dodecyl sulfate (SDS), sodium bis(2-ethylhexyl)sulfosuccinate
      (AOT), and sodium oleate were sorbed on positively charged aluminum hydroxide at
      pH 7 and formed hydrophobic aggregates that can incorporate hydrophobic organic
      pollutants in water. Because of the hydrophobic interaction and decrease in the
      positive charge, surfactant-Al(OH)(3) was coagulated into precipitates that can
      readily be separated from water. Hydrophobic organic pollutants such as
      alkylphenols, polycyclic aromatic hydrocarbons, estrogens, chlorinated
      antifungals, and pesticides were well collected to the precipitates and thus
      efficiently removed from water. The collection of hydrophobic organic pollutants
      was correlated to their aqueous-octanol distribution coefficient. The
      decomposition of hydrophobic organic pollutants was examined using a bacterial
      agent (Bacillus subtilis). Hydrophobic organic compounds collected to AOT
      Al(OH)(3) or sodium oleate-Al(OH)(3) were insufficiently decomposed. On the other
      hand, nonylphenol, octylphenol, and pendimethalin collected to SDS-Al(OH)(3) were
      decomposed within 1 week. The decomposition was accelerated by the collection to
      SDS-Al(OH)(3).

PMID- 21193214
TI  - Extracellular Polymeric Substances diversity of biofilms grown under contrasted
      environmental conditions.
AB  - Extracellular Polymeric Substances (EPS) analysis was undertaken on three
      biofilms grown under different feeding conditions and offering diverging
      microbial activities and structural characteristics. EPS were extracted by a
      multi-method protocol including sonication, Tween and EDTA treatments and were
      characterized by size exclusion chromatography (SEC). Tween and sonication
      extracts presented higher EPS size diversity compared to EDTA extracts. EPS size
      diversity also increased with microbial functions within the biofilms and a
      specific 25-50 kDa cluster was identified only in extracts from biofilms
      presenting autotrophic activity. Another specific size cluster (180 kDa) occurred
      in Tween extracts provided from the mechanically stable biofilms. Such specific
      EPS appear as potential indicators for describing microbial and structural
      properties of biofilms. This study brings new elements for designing EPS
      fractionation and shows that size distribution analysis is an interesting tool to
      relate EPS diversity with macro-scale characteristics of biofilms.

PMID- 21193215
TI  - Impact of dissolved organic matter on colloid transport in the vadose zone:
      deterministic approximation of transport deposition coefficients from polymeric
      coating characteristics.
AB  - Although numerous studies have been conducted to discern colloid transport and
      stability processes, the mechanistic understanding of how dissolved organic
      matter (DOM) affects colloid fate in unsaturated soils (i.e., the vadose zone)
      remains unclear. This study aims to bridge the gap between the physicochemical
      responses of colloid complexes and porous media interfaces to solution chemistry,
      and the effect these changes have on colloid transport and fate. Measurements of
      adsorbed layer thickness, density, and charge of DOM-colloid complexes and
      transport experiments with tandem internal process visualization were conducted
      for key constituents of DOM, humic (HA) and fulvic acids (FA), at acidic, neutral
      and basic pH and two CaCl(2) concentrations. Polymeric characteristics reveal
      that, of the two tested DOM constituents, only HA electrosterically stabilizes
      colloids. This stabilization is highly dependent on solution pH which controls
      DOM polymer adsorption affinity, and on the presence of Ca(+2) which promotes
      charge neutralization and inter-particle bridging. Transport experiments indicate
      that HA improved colloid transport significantly, while FA only marginally
      affected transport despite having a large effect on particle charge. A transport
      model with deposition and pore-exclusion parameters fit experimental breakthrough
      curves well. Trends in deposition coefficients are correlated to the changes in
      colloid surface potential for bare colloids, but must include adsorbed layer
      thickness and density for sterically stabilized colloids. Additionally, internal
      process observations with bright field microscopy reveal that, under optimal
      conditions for retention, experiments with FA or no DOM promoted colloid
      retention at solid-water interfaces, while experiments with HA enhanced colloid
      retention at air-water interfaces, presumably due to partitioning of HA at the
      air-water interface and/or increased hydrophobic characteristics of HA-colloid
      complexes.

PMID- 21193216
TI  - Temporal study of Helicobacter pylori presence in coastal freshwater, estuary and
      marine waters.
AB  - Helicobacter pylori, a gastric pathogen, is believed to be transmitted via the
      fecal-oral route as well as the oral-oral route. Its presence and viability in
      environmental waters is not well characterized. The goals of this study were to
      test H. pylori presence via molecular methods in freshwater, estuarine and beach
      sites in Delaware over both short and long time scales and to establish whether
      fecal indicator bacteria, including total Enterococcus and human-specific
      Bacteroidetes species, are predictive of the pathogen in these waters. The
      presence of Helicobacter pylori was initially tested by PCR with newly designed
      23S rRNA gene primers against Helicobacter spp. and confirmed by sequencing. Two
      coastal beach sites were repeatedly positive in 2007. Clone library analysis
      indicated the persistence of one operational taxonomic unit (OTU) over time at
      one site. Detection of H. pylori was also determined by PCR assays from DNA and
      RNA for the 16S rRNA gene, as well as DNA for the ureA and cagA genes.
      Approximately 21% of the samples were positive for H. pylori 16S rRNA gene and
      80% of those were also positive for H. pylori 16S rRNA, indicating that this
      potential pathogen is not only present in natural waters, but also probably
      viable. There was no correlation between the occurrence of H. pylori and fecal
      indicator bacteria, suggesting that standard water quality tests are ineffective
      in predicting the presence of this pathogen in natural waters. These results
      demonstrate the widespread presence of potentially viable H. pylori in coastal
      marine and estuarine waters. Additionally, the repeatedly positive samples
      indicate either a continual contamination source or persistence of H. pylori in
      marine waters.

PMID- 21193217
TI  - Persistent organic pollutants in food items collected in Hong Kong.
AB  - This study aims to investigate levels of POPs in meat, edible oils, nuts, milk
      and wine collected from Hong Kong. Naphthalene, pp-DDE, beta-, gamma-HCH and PBDE
      47 were detected in most of the food items. Goose liver accumulated the highest
      PAHs (47.9ngg(-1) wet wt), DDTs (25.6), HCHs (13.0), PCBs (4.17), PBDEs (468pgg(
      1) wet wt) among all the selected food. Meat and nut groups had significant
      (p<0.01 or 0.05) correlations between lipid contents and concentrations of PAHs
      (meat: r=0.878), HCHs (meat: r=0.753), DDTs (meat: r=0.937; nuts: r=0.968) and
      PCBs (meat: r=0.832; nut: r=0.946). The concentrations of DDTs, HCHs and PCBs in
      vegetable oil were lower, but HCHs in fish oil were higher, when compared with
      other countries. The concentrations of PAHs, DDTs, PCBs and PBDEs in food tested
      in the present study were all below various safety guidelines.

PMID- 21193218
TI  - Determination of chloramphenicol, enrofloxacin and 29 pesticides residues in
      bovine milk by liquid chromatography-tandem mass spectrometry.
AB  - A sensitive method for determination of chloramphenicol, enrofloxacin and 29
      pesticides residues in bovine milk by high-performance liquid chromatography
      tandem mass spectrometry (HPLC-MS/MS) was developed. Residues of the targets were
      extracted from milk with acetonitrile, cleaned up by C(18)-SPE cartridge, and
      then determined by HPLC-MS/MS. The MS detection was operated in positive or
      negative ionization mode, depending on the compounds. For confirmation of each
      target compound, two precursor ion>product ion transitions were selected by multi
      reaction monitoring mode (MRM). The method showed good linearity for all the
      tested compounds over the studied concentration range with correlation
      coefficient higher than 0.9910. Recoveries for the studied compounds at three
      spiked levels (0.05, 0.10, 0.19mgkg(-1)) in bovine milk were in the range of 71
      107% with RSDs not larger than 13.7%, except that recoveries of trifluralin
      ranged between 62% and 70% at the spiked levels. Limits of quantitation for the
      analytes were estimated to range between 0.03*10(-3) and 14.5*10(-3)mgkg(-1). The
      proposed method was applied for the determination of the analytes residues in
      real samples. The found levels of the analytes in milk samples were lower than
      maximum residues levels (MRL).

PMID- 21193219
TI  - Zero-valent iron nanoparticles in treatment of acid mine water from in situ
      uranium leaching.
AB  - Acid mine water from in situ chemical leaching of uranium (Straz pod Ralskem,
      Czech Republic) was treated in laboratory scale experiments by zero-valent iron
      nanoparticles (nZVI). For the first time, nZVI were applied for the treatment of
      the real acid water system containing the miscellaneous mixture of pollutants,
      where the various removal mechanisms occur simultaneously. Toxicity of the
      treated saline acid water is caused by major contaminants represented by aluminum
      and sulphates in a high concentration, as well as by microcontaminants like As,
      Be, Cd, Cr, Cu, Ni, U, V, and Zn. Laboratory batch experiments proved a
      significant decrease in concentrations of all the monitored pollutants due to an
      increase in pH and a decrease in oxidation-reduction potential related to an
      application of nZVI. The assumed mechanisms of contaminants removal include
      precipitation of cations in a lower oxidation state, precipitation caused by a
      simple pH increase and co-precipitation with the formed iron oxyhydroxides. The
      possibility to control the reaction kinetics through the nature of the surface
      stabilizing shell (polymer vs. FeO nanolayer) is discussed as an important
      practical aspect.

PMID- 21193220
TI  - Assessment of polychlorinated dibenzo-p-dioxin and dibenzofuran emissions from a
      hazardous waste incineration plant using long-term sampling equipment.
AB  - The aim of this work is to evaluate the performance of a continuous monitoring
      system for the analysis of the mass concentration of PCDD/Fs from stationary
      sources. Data was acquired from a modern, state of the art, hazardous waste
      thermal treatment plant for a period of more than 2 years using a commercial
      available continuous monitoring system. The study consisted of a total of 16
      samples, collected in periods from 1 week to 2 months resulting in an average of
      360 m3 sampled flue gas per sample. The study showed the system was able to
      confirm that for a period of more than 2 years the plant was complying with the
      limit of 0.1 ng I-TEQ/Nm(3). In addition, the data showed the typical fingerprint
      of such installations which is useful for example in impact studies. Long-term
      samples were compared to five short-term samples (6 h) collected every 6 months
      during the study period. Principal component analysis was applied to PCDD/Fs
      obtained data as useful statistical tool to find out trends and similarities
      between different samples. Improvement in terms of representativeness of data was
      achieved through continuous assessment since the starts of the project. The
      obtained data was further used to determine the emission factor for this activity
      and the total annual PCDD/Fs release to the atmosphere.

PMID- 21193221
TI  - Occurrence and distribution of sediment-associated insecticides in urban
      waterways in the Pearl River Delta, China.
AB  - Sediment-associated pesticides, including organochlorine (OCP), organophosphate
      (OP), and pyrethroid insecticides, were analyzed in urban waterways in three
      cities (Guangzhou, Dongguan, and Shenzhen) in the Pearl River Delta (PRD), China.
      The OCPs represented 27.2% of the detectable insecticides in sediment, and
      chlordanes, DDTs, and endosulfans were the most frequently detected OCPs. The
      currently used insecticide chlorpyrifos was the only OP detected above the
      reporting limit (RL), with concentrations ranging from <RL to 100 ng g(-1) dry
      weight (dw). Additionally, pyrethroids were detected in all sediments with the
      sum pyrethroid concentrations ranging from 4.26 to 384 ng g(-1) dw and this
      represented 64.9% of the sum insecticide concentration. Despite their widespread
      use, no studies have been conducted investigating the occurrence and distribution
      of pyrethroids in China. As the first report of pyrethroids in urban waterways in
      China, the current study found cypermethrin was the most abundant insecticide
      detected in the PRD at concentrations ranging from 1.44 to 219 ng g(-1) dw.
      Spatially, sediment from more populous and urbanized areas (Shenzhen and Tianhe
      district in Guangzhou) had higher insecticide residues than less populous
      agricultural areas. In the more modernized city of Shenzhen, the OCPs were seldom
      detected, whereas more diverse patterns of pyrethroids were observed. Potential
      sources of these insecticides, especially the frequently detected pyrethroids,
      were most likely from pest control during urban landscaping maintenance and from
      abatement programs targeting mosquitoes and ants. Results suggested that a shift
      in application pattern and elevated urbanization increased accumulation of
      currently used insecticides like pyrethroids in sediment, and made them the
      predominate insecticides in the PRD urban waterways.

PMID- 21193222
TI  - SOX9 expression increases with malignant potential in tumors from patients with
      neurofibromatosis 1 and is not correlated to desert hedgehog.
AB  - We investigated the expression of SOX9, a transcription factor linked to the
      hedgehog pathways, and desert hedgehog, previously shown to be expressed in a
      malignant peripheral nerve sheath tumor cell line, in neurofibromatosis 1 tumors
      (neurofibromas and malignant peripheral nerve sheath tumor), and in a group of
      sporadic spindle cell sarcomas. We found that SOX9 was expressed in Schwann cells
      from neurofibromatosis 1 tumors, and was significantly up-regulated in malignant
      peripheral nerve sheath tumor versus neurofibromas at the protein level (P <
      .0001) and in malignant peripheral nerve sheath tumor and plexiform neurofibroma
      as compared to diffuse tumors at the mRNA level (P = .002 and P = .009,
      respectively). SOX9, however, was not a specific feature of malignant peripheral
      nerve sheath tumor because a significant proportion of spindle cell sarcomas
      unrelated to neurofibromatosis 1 were also positive. Interestingly, within
      neurofibromas, SOX9 expression correlated to the histology mostly found in
      plexiform areas, whereas it was negative or weak in diffuse neurofibroma (P <
      .0001). In sporadic sarcomas, the proportion of positive cells was actually
      heterogeneous among cases. Desert hedgehog expression was mostly found in
      sarcomas (P = .0002), but diffuse staining was only seen in non-neurofibromatosis
      1 tumors, whereas malignant peripheral nerve sheath tumor displayed only focal
      expression. Finally, we found no significant correlation between the expression
      of SOX9 and desert hedgehog, and neither SOX9 nor desert hedgehog expression was
      correlated to the histoprognostic grade in sarcomas. Altogether, these results
      indicate that, although not a specific feature of neurofibromatosis 1 tumors,
      SOX9 may play a role in the development of malignant peripheral nerve sheath
      tumor in patients with neurofibromatosis 1 and does not appear to be linked to
      autocrine stimulation by the desert hedgehog signaling pathway.

PMID- 21193223
TI  - The nuclear to cytoplasmic shift of ING5 protein during colorectal carcinogenesis
      with their distinct links to pathologic behaviors of carcinomas.
AB  - Inhibitor of growth 5, a tumor suppressor protein, can interact with p53, thereby
      inhibiting cell growth and inducing apoptosis. Inhibitor of growth 5
      overexpression results in a reduction in colony-forming efficiency and cell
      population in S phase. To clarify the roles of inhibitor of growth 5 in
      tumorigenesis and progression of colorectal carcinomas, we examined inhibitor of
      growth 5 expression by immunohistochemistry on a tissue microarray containing
      colorectal carcinomas (n = 306), adenomas (n = 69), and nonneoplastic mucosa (n =
      288) and compared this with clinicopathologic parameters of the carcinomas. In
      addition, inhibitor of growth 5 expression in colorectal carcinoma tissues and
      cell lines (DLD-1, HCT-15, SW480, and WiDr) was analyzed by Western blot and
      reverse transcriptase-polymerase chain reaction. It was found that the inhibitor
      of growth 5 protein was localized to the nuclei of colon carcinoma cells with no
      differences at mRNA levels. Among 18 frozen samples of colorectal carcinoma,
      significantly increased expression of inhibitor of growth 5 protein was observed
      in the carcinoma in comparison with adjacent mucosa in 14 cases (77.8%; P < .05),
      and 71.4% (10/14) of carcinoma cases exhibited up-regulated inhibitor of growth 5
      mRNA expression. Decreased inhibitor of growth 5 expression was detected by
      immunohistochemistry in colorectal carcinoma, compared with non-neoplastic mucosa
      and adenoma (P < .05). Nuclear inhibitor of growth 5 expression was negatively
      correlated with tumor size, depth of invasion, degree of dedifferentiation, and
      Union Internationale Contre le Cancer staging (P < .05). In contrast, cytoplasmic
      inhibitor of growth 5 expression was positively correlated with depth of
      invasion, lymphatic invasion, and Union Internationale Contre le Cancer staging
      (P < .05). It was suggested that aberrant inhibitor of growth 5 expression may
      contribute to pathogenesis, growth, and invasion of colorectal carcinomas and
      could be considered as a promising marker to gauge aggressiveness of colorectal
      carcinomas.

PMID- 21193224
TI  - Cell adhesion and communication proteins are differentially expressed in melanoma
      progression model.
AB  - Cutaneous melanoma is an aggressive cancer derived from skin melanocytes. Tissue
      microarrays are being used to evaluate the roles of numerous proteins implicated
      in some of the pathways involved in melanoma pathogenesis. Based on a previous
      study using a complementary DNA microarray platform, the aim of this study was to
      evaluate the immunohistochemical expression of the adhesion and communication
      molecules connexin 43, desmocollin 3, cytokeratin 5, kallikrein 6, and kallikrein
      7 in a melanoma progression model. We analyzed 59 common nevi, 22 atypical nevi,
      and 162 invasive and 29 metastatic melanomas on tissue microarrays using digital
      microscopy. The expression of desmocollin 3 and connexin 43 was higher in
      melanomas (P < .001). Kallikrein 6 expression was higher in melanomas than in
      common nevi (P < .006). The expression of cytokeratin 5 and kallikrein 7 was
      higher in atypical nevi than in melanomas (P < .001) and was higher in melanomas
      than in common nevi (P < .001). The expression of desmocollin 3 and connexin 43
      in melanomas indicates loss of cell-cell interactions, which starts in the early
      steps of the melanoma progression model. Keratin expression in melanomas may play
      a particular role during melanocyte development. The expression of kallikrein 7
      and kallikrein 6 in melanomas may be responsible for the loss of cell-cell
      adhesion.

PMID- 21193225
TI  - Monitoring and analysis of combustion aerosol emissions from fast moving diesel
      trains.
AB  - In this paper we report the results of the detailed monitoring and analysis of
      combustion emissions from fast moving diesel trains. A new highly efficient
      monitoring methodology is proposed based on the measurements of the total number
      concentration (TNC) of combustion aerosols at a fixed point (on a bridge
      overpassing the railway) inside the violently mixing zone created by a fast
      moving train. Applicability conditions for the proposed methodology are
      presented, discussed and linked to the formation of the stable and uniform mixing
      zone. In particular, it is demonstrated that if such a mixing zone is formed, the
      monitoring results are highly consistent, repeatable (with typically negligible
      statistical errors and dispersion), stable with respect to the external
      atmospheric turbulence and result in an unusual pattern of the aerosol evolution
      with two or three distinct TNC maximums. It is also shown that the stability and
      uniformity of the created mixing zone (as well as the repeatability of the
      monitoring results) increase with increasing length of the train (with an
      estimated critical train length of ~10 carriages, at the speed of ~150km/h). The
      analysis of the obtained evolutionary dependencies of aerosol TNC suggests that
      the major possible mechanisms responsible for the formation of the distinct
      concentration maximums are condensation (the second maximum) and thermal
      fragmentation of solid nanoparticle aggregates (third maximum). The obtained
      results and the new methodology will be important for monitoring and analysis of
      combustion emissions from fast moving trains, and for the determination of the
      impact of rail networks on the atmospheric environment and human exposure to
      combustion emissions.

PMID- 21193226
TI  - The neurodegenerative process in a neurotoxic rat model and in patients with
      Huntington's disease: histopathological parallels and differences.
AB  - Although Huntington's disease (HD) occurs only in humans, the use of animal
      models is crucial for HD research. New genetic models may provide novel insights
      into HD pathogenesis, but their relevance to human HD is problematic,
      particularly owing to a lower number of typically degenerated and dying striatal
      neurons and consequent insignificant reactive gliosis. Hence, neurotoxin-induced
      animal models are widely used for histopathological studies. Unlike in humans,
      the neurodegenerative process (NDP) of the HD phenotype develops very fast after
      the application of quinolinic acid (QA). For that reason, we compared three
      groups of rats in more advanced stages (1-12 months) of the QA lesion with 3
      representative HD cases of varying length and grade. The outcomes of our long
      term histological study indicate that significant parallels may be drawn between
      HD autopsies and QA-lesioned rat brains (particularly between post-lesional
      months 3 and 9) in relation to (1) the progression of morphological changes
      related to the neuronal degeneration, primarily the rarefaction of neuropil
      affecting the density as well as the character of synapses, resulting in severe
      striatal atrophy and (2) the participation of oligodendrocytes in reparative
      gliosis. Conversely, the development and character of reactive astrogliosis is
      principally conditioned by the severity of striatal NDP in the context of neuron
      glia relationship. Despite the above-described differences, morphological
      patterns in which the components of striatal parenchyma react to the progression
      of NDP are similar in both human and rat brains. Our study specifies the
      possibilities of interpreting the morphological findings gained from the QA
      induced animal model of HD in relation to HD post-mortem specimens.

PMID- 21193228
TI  - The transfection of multipotent neural precursor/stem cell transplant populations
      with magnetic nanoparticles.
AB  - Multipotent neural precursor/stem cells (NPCs) are a major transplant population
      with key properties to promote repair in several neuropathological conditions.
      Magnetic nanoparticle (MNP)-based vector systems, in turn, offer a combination of
      key benefits for cell therapies including (i) safety (ii) delivery of therapeutic
      biomolecules (DNA/siRNA) enhanceable by 'magnetofection' approaches (iii)
      magnetic cell targeting of MNP-labelled cells to injury sites and (iv) non
      invasive imaging of MNP-labelled transplant populations for cell tracking.
      However, the applications of the versatile MNP platform for NPC transplantation
      therapies have received limited attention so far. We have evaluated the potential
      of MNP vectors for gene transfer to NPCs using a neurosphere culture model
      system; we also assessed repeat transfection ("multifection") and repeat
      transfection plus applied magnetic field ("magneto-multifection") strategies [to
      enhance transfection efficiency]. We show for the first time that MNPs can safely
      mediate single/combinatorial gene delivery to NPCs. Multifection approaches
      significantly enhanced transfection with negligible toxicity; no adverse effects
      were observed on stem cell proliferation/differentiation. "Multifected" NPCs
      survived and differentiated in 3D neural tissue arrays post-transplantation. Our
      findings demonstrate that MNPs offer a simple and robust alternative to the viral
      vector systems currently used widely to transfect neural stem cells in
      neurobiology/neural transplantation research.

PMID- 21193227
TI  - Risk factors for poor prognosis in microinvasive adenocarcinoma of the uterine
      cervix (IA1 and IA2): a pooled analysis.
AB  - OBJECTIVE: To identify adverse risk factors for FIGO IA1 and IA2 cervical
      adenocarcinoma. METHODS: PubMed was used to identify all microinvasive
      adenocarcinoma cases. Case specific data pooled for 35 "high risk" microinvasive
      adenocarcinoma (MIAC), defined as cases with lymph node or lymphovascular space
      involvement, positive surgical margins, or recurrence was compared with 478 "low
      risk" cases abstracted from the SEER database (1988-1997). Statistical methods
      included non-paired t and Fisher's Exact tests. RESULTS: Survival for 1A1 and 1A2
      MIAC is 99% and 98%, respectively. Significantly more 1A2 patients underwent
      aggressive radical surgery and received postoperative treatment. Parametrial
      involvement was rare (1/373 cases). Significantly more "high-risk" cases were of
      endometrioid histology (6/34 vs. 14/478, p=0.001), whereas adenocarcinoma
      (p=0.046) and mucinous (p=0.021) tumors were observed in the "low-risk" group.
      Among the "high-risk" cases with at least 5 years follow-up, 1.4% has recurred or
      died. CONCLUSIONS: Endometrioid histology may be associated with late recurrence
      and worse survival in stage 1A1 and 1A2 MIAC.

PMID- 21193230
TI  - Predominance of BDE-209 and other higher brominated diphenyl ethers in eggs of
      white stork (Ciconia ciconia) colonies from Spain.
AB  - Polybrominated diphenyl ethers (PBDEs) are ubiquitous pollutants for which there
      is still a lack of knowledge about the environmental behavior and fate of the
      higher brominated congeners (octa- to deca-BDEs). In this study, the PBDE content
      and congener profiles in failed eggs from two colonies of white stork (Ciconia
      ciconia) in Spain were studied. The average total PBDE concentration was 1.64ng/g
      (wet weight, w.w.) for the rural colony and 9.08ng/g (w.w.) for the urban colony.
      Higher brominated BDEs dominated the congener profiles of both colonies. Of
      particular interest was the determination of BDE-209 as the dominant congener
      accounting for 44.1% and 38.6% of the total PBDE content in the rural and urban
      colonies, respectively. BDE-202, considered an indicator of BDE 209
      debromination, was detected in 83% and all of the samples from rural and urban
      colonies, respectively. The observed congener profile in which BDE-207>BDE
      208>BDE-206 does not correspond to any known technical PBDE mixture and is
      evidence for possible BDE-209 degradation.

PMID- 21193229
TI  - Thapsigargin activates Ca2+ entry both by store-dependent, STIM1/Orai1-mediated,
      and store-independent, TRPC3/PLC/PKC-mediated pathways in human endothelial
      cells.
AB  - The ER Ca2+ sensor STIM1 and the Ca2+ channel Orai1 are key players in store
      operated Ca2+ entry (SOCE). In addition, channels from the TRPC family were also
      shown to be engaged during SOCE, while their precise implication remains
      controversial. In this study, we investigated the molecular players involved in
      SOCE triggered by the SERCA pump inhibitor thapsigargin in an endothelial cell
      line, the EA.hy926. siRNA directed against STIM1 or Orai1 reduced Ca2+ entry by
      about 50-60%, showing that a large part of the entry is independent from these
      proteins. Blocking the PLC or the PKC pathway completely abolished thapsigargin
      induced Ca2+ entry in cells depleted from STIM1 and/or Orai1. The phorbol ester
      PMA or the DAG analog OAG restored the Ca2+ entry inhibited by PLC blockers,
      showing an involvement of PLC/PKC pathway in SOCE. Using pharmacological
      inhibitors or siRNA revealed that the PKCeta is required for Ca2+ entry, and
      pharmacological inhibition of the tyrosine kinase Src also reduced Ca2+ entry.
      TRPC3 silencing diminished the entry by 45%, while the double STIM1/TRPC3
      invalidation reduced Ca2+ entry by more than 85%. Hence, in EA.hy926 cells, TG
      induced Ca2+ entry results from the activation of the STIM1/Orai1 machinery, and
      from the activation of TRPC3.

PMID- 21193231
TI  - What are distributed lag models of particulate matter air pollution estimating
      when there are populations of frail individuals?
AB  - The three-state (healthy, frail, and dead) population model is commonly used in
      time-series investigations of mortality displacement and particulate matter air
      pollution (PM). In this paper, the author proposes a new population model, called
      the mixture population model, that by allowing PM to have differential effects on
      individuals in the population, extends the population models currently used in
      investigations of mortality displacement. Using this new model, the properties of
      distributed lag models (DLM) of PM are investigated. In particular, the author
      derives a relationship between the parameters of the proposed population model
      and the estimates obtained from a DLM fitted to mortality arising from the model.
      This relationship provides insight into the interrelationships between the size
      of the frail population, the number of lags of PM included in a DLM and the
      proportion of the effect of PM on the healthy population that is estimable. The
      relationship will guide and contextualize future investigations by providing
      researchers with the knowledge to assess the consequences of the number of lags
      of PM included in a DLM in terms of what they can plausibly infer about the
      effect of PM on mortality based on this choice of lag.

PMID- 21193232
TI  - Hearing assessment in congenital diaphragmatic hernia survivors.

PMID- 21193233
TI  - Differences in cognitive performance, level of dependency and quality of life
      (QoL), related to age and cognitive status in a sample of Spanish old adults
      under and over 80 years of age.
AB  - The main objective of this study was to analyze the similarities and differences
      in cognitive performance, level of dependency, cognitive plasticity and QoL in a
      sample of young-old adults and old-old adults, bearing in mind both the age-group
      (under or over 80 years) and the cognitive status of the participants. The study
      population consisted of 220 people living in sheltered accommodation for elderly
      people in the South of Spain, with an average age of 80.75 years. Participants
      were evaluated by means of cognitive performance tests, a QoL questionnaire, a
      depression scale and a dependency assessment scale. The results indicate that the
      main differences in the variables analyzed are due to the cognitive status of the
      sample and not to the fact that the participants are under or over 80 years of
      age. The findings show that major inter-individual differences in this stage of
      life depend not only on age but also on cognitive status, which is thus an
      important factor to take into account when working with this sector of the
      population.

PMID- 21193234
TI  - Diagnostic performance of two types of low radiation exposure protocol for
      prospective ECG-triggering multidetector computed tomography angiography in
      assessment of coronary artery bypass graft.
AB  - BACKGROUND: Multidetector computed tomography (MDCT) is useful in evaluation of
      coronary artery bypass graft (CABG). However, radiation exposure is a reason for
      concern. We compared diagnostic performance and effective dose of a new dedicated
      post-processing reconstruction algorithm with BMI-adapted scanning protocol (MDCT
      XTe) vs. standard prospective ECG-triggering protocol (MDCT-XT) and retrospective
      ECG-triggering (MDCT-Helical), compared to invasive coronary angiography (ICA),
      in the assessment of grafts and nongrafted or distal runoff coronary arteries.
      METHODS: One hundred and nineteen patients with 277 grafts were randomized to
      Group 1 based on BMI-adapted scanning protocol with prospective ECG-triggering
      (40 patients), Group 2 with prospective ECG-triggering (39 patients) and Group 3
      (40 patients) with retrospective ECG-triggering. Data were acquired using 64
      slice MDCT. RESULTS: MDCT correctly assessed the patency of all CABG in 3 groups.
      After comparison with ICA, MDCT was able to correctly detect the occlusion or
      stenosis of CABG in all groups, with the exception of one case of Group 3. In
      Group 3 sensitivity, specificity, positive predictive value, negative predictive
      value and accuracy of CABG evaluation were 100%, 98.4%, 96.7%, 100% and 98.9%,
      respectively. In Groups 1 and 2 the diagnostic accuracy of CABG evaluation was
      100%. Effective radiation dose was 3.5+/-1.4mSv in Group 1 vs. 7.4+/-2.6mSv in
      Group 2 vs. 27.8+/-9.4mSv in Group 3. CONCLUSIONS: Our results indicated that
      MDCT-XTe and MDCT-XT have a diagnostic performance in the evaluation of CABG
      similar to MDCT-Helical, with a significant reduction of radiation exposure,
      specially for MDCT-XTe.

PMID- 21193235
TI  - The small intestine in cardiac cachexia: a forgotten player of the game.

PMID- 21193236
TI  - Combined effects of up- and downstream therapies on atrial fibrillation in a
      canine rapid stimulation model.
AB  - BACKGROUND: Recent reports suggest angiotensin receptor blockers (ARBs) and some
      antiarrhythmic agents affect atrial remodeling in atrial fibrillation (AF). We
      evaluated the effect of combination therapy with olmesartan (Olm) and bepridil
      (Bep) in a canine model of AF. METHODS AND RESULTS: An atrial stimulation device
      was implanted in 10 dogs undergoing 6-week pacing at 400 bpm. They were divided
      into Olm (2 mg/kg/day) (n=5) and Olm+Bep (Olm, 2 mg/kg/day; Bep, 10 mg/kg/day)
      groups (n=5). Atrial effective refractory period (AERP), conduction velocity
      (CV), and AF inducibility were evaluated weekly, and hemodynamics, atrial
      histology, and mRNA expression and protein expression of ion-channel and gap
      junction-related molecules at 6 weeks. Data were compared between groups and with
      non-pacing control and pacing-control groups from our previous report. The pacing
      control group exhibited shortened AERP, decreased CV, increased AF inducibility
      and tissue fibrosis, and down-regulated L-type Ca(2+) channel (LCC), SCN5A, Kv4.3
      and connexin43 (Cx43). By comparison, the Olm group exhibited suppression of the
      decrease in CV and of the increase in AF inducibility, but no change in AERP
      shortening. The Olm+Bep group exhibited suppression of AERP shortening as well as
      the greatest decrease in AF inducibility. Histologically, tissue fibrosis was
      suppressed in Olm and Olm+Bep groups. Down-regulation of Cx43 was partly
      suppressed in the Olm group while that of LCC, SCN5A, and Cx43 was suppressed in
      the Olm+Bep group. CONCLUSION: Olm and Bep in combination suppressed AF
      inducibility more strongly than Olm alone, and may be more useful in the
      suppression of AF.

PMID- 21193237
TI  - Duty-cycled unipolar/bipolar versus conventional radiofrequency ablation in
      paroxysmal and persistent atrial fibrillation.
AB  - BACKGROUND: Duty-cycled (DC) radiofrequency ablation (RFA) for atrial
      fibrillation (AF) has been introduced, however, data on large patient series and
      comparison to conventional RFA are scarce. METHODS: Between 2006 and 2008 DC RFA
      was performed in 209 consecutive patients (143 (68%) paroxysmal and 66 (32%)
      persistent AF). As controls served 211 patients, 155 (73%) with paroxysmal and 56
      (27%) with persistent AF (p=0.3). In DC RFA, the pulmonary veins (PV) were
      isolated followed by ablation at the septum and left atrium, if AF persisted.
      Conventional PV isolation was followed by anatomical lines at the roof and mitral
      isthmus. RESULTS: Freedom of paroxysmal AF was demonstrated after 1.08 DC RFA
      procedures per patient in 82% and after 1.19 conventional procedures in 87% after
      8.5 +/- 6.5 months (ns). In persistent AF, success rates were 79% after 1.35 DC
      RFA procedures and 80% after 1.34 conventional procedures after 11.5 +/- 8.5
      months (ns). The subgroup analysis of 119 patients with follow-up >= 12 months
      (17.5 [14.1-23.6] months) showed similar results. Left atrial flutter occurred in
      3% and 8% after paroxysmal AF ablation (p < 0.05) and in 12% and 23% after
      persistent AF ablation (p=0.1). Multivariate predictors for success in both
      groups were age, left atrial size, presence of persistent vs. paroxysmal AF and
      previous pacemaker implantation, but not the ablation technique used. Non-fatal
      complications were seen in 2.8% with no differences between the groups.
      CONCLUSION: Outcome in DC RFA is similar to conventional RFA with a final success
      rate exceeding 80% in both paroxysmal and persistent AF in the absence of fatal
      complications.

PMID- 21193238
TI  - Fetal and maternal microchimerism: a boost for mom and baby?

PMID- 21193239
TI  - Cardiac rehabilitation in multicultural populations.

PMID- 21193240
TI  - Postpartum cardiomyopathy complicated with upper-extremity deep vein thrombosis
      and pulmonary embolism.

PMID- 21193241
TI  - Long term outcome of routine early versus late transfer for coronary angiography
      following presumably successful thrombolysis for ST-segment elevation myocardial
      infarction.

PMID- 21193242
TI  - Visual loss due to cardiac calcified amorphous tumor: a case report and brief
      review of the literature.

PMID- 21193243
TI  - Antigen carbohydrate 125 in heart failure: not just a surrogate for serosal
      effusions?

PMID- 21193244
TI  - Diabetes-related change in physical disability from midlife to older adulthood:
      evidence from 1996-2003 Survey of Health and Living Status of the Elderly in
      Taiwan.
AB  - One in five older adults in Taiwan have been diagnosed with diabetes. This study
      drew on disability data for 5121 nationally representative middle-aged and older
      adults from the 1996-2003 Survey of Health and Living Status of the Elderly in
      Taiwan (SHLSET). By employing cohort sequential design and multilevel models, it
      combined cross-sectional and longitudinal evidence to characterize the age
      trajectory of physical disability from midlife to older adulthood and to discern
      the extent to which diabetes contributes to the variation in that trajectory. The
      main effects of diabetes and diabetes * age interaction in the fully controlled
      model provide evidence that diabetes independently and consistently changes
      physical functioning over and above natural aging processes in Taiwanese adults.
      In addition, while adding diabetes in the age trajectory of physical disability
      explained 3.2% and 1.6% of the variance in levels of and linear changes in
      physical disability trajectory, respectively, further adding follow-up status,
      sociodemographic factors and comorbidities altogether explained 40.5% and 29.1%
      of the variance in levels of and linear changes in that trajectory. These results
      imply that preventing the incidence of diabetes-related comorbidities may reduce
      the deterioration in both levels of and rates of change in physical disability.

PMID- 21193245
TI  - Reduced expression of arrestin beta 2 by graft monocytes during acute rejection
      of rat kidneys.
AB  - During acute rejection, numerous pro-inflammatory and cytotoxic monocytes
      accumulate in the vasculature of experimental renal allografts. Arrestins (ARRBs)
      are cellular regulators of inflammation, but nothing is known about their
      expression during rejection. Intravascular mononuclear graft leukocytes were
      isolated 4 days after kidney transplantation. ARRB1 and ARRB2 mRNA expression was
      reduced in blood leukocytes from allografts undergoing acute rejection, whereas
      on the protein level only ARRB2 was changed. Flow cytometry and confocal
      microscopy revealed ARRB1 and ARRB2 expression by monocytes and T cells, with a
      selective decrease in ARRB2 expression in monocytes during acute rejection. I
      kappaB directly interacted with ARRB2 and the levels of both proteins strongly
      correlated. Concomitantly, the mRNA expression of NF-kappaB targeted genes
      increased. Our results suggest that activation of blood monocytes in renal
      isografts is dampened by high ARRB2 levels. During acute rejection, ARRB2 levels
      are reduced and classical monocyte activation is enabled via NF-kappaB
      activation.

PMID- 21193246
TI  - Duplication of amyloid precursor protein (APP), but not prion protein (PRNP) gene
      is a significant cause of early onset dementia in a large UK series.
AB  - Amyloid precursor protein gene (APP) duplications have been identified in screens
      of selected probands with early onset familial Alzheimer's disease (FAD). A
      causal role for copy number variation (CNV) in the prion protein gene (PRNP) in
      prion dementias is not known. We aimed to determine the prevalence of copy number
      variation in APP and PRNP in a large referral series, test a screening method for
      detection of the same, and expand knowledge of clinical phenotype. We used a 3
      tiered screening assay for APP and PRNP duplication (exonic real-time
      quantitative polymerase chain reaction [exon-qPCR], fluorescent microsatellite
      quantitative PCR [fm-q-PCR], and Illumina array [Illumina Inc., San Diego, CA,
      USA]) for analysis of a heterogeneous referral series comprising 1531 probands.
      Five of 1531 probands screened showed APP duplication, a similar prevalence to
      APP missense mutation. Real-time quantitative PCR and fluorescent microsatellite
      quantitative PCR were similar individually but are theoretically complementary;
      we used Illumina arrays as our reference assay. Two of 5 probands were from an
      autosomal dominant early onset Alzheimer's disease (familial Alzheimer's disease)
      pedigree. One extensive, noncontiguous duplication on chromosome 21 was
      consistent with an unbalanced translocation not including the Down's syndrome
      critical region. Seizures were prominent in the other typical APP duplications. A
      range of imaging, neuropsychological, cerebrospinal fluid, and pathological
      findings are reported that extend the known phenotype. APP but not PRNP
      duplication is a significant cause of early onset dementia in the UK. The
      recognized phenotype may be expanded to include the possibility of early seizures
      and apparently sporadic disease which, in part, may be due to different
      mutational mechanisms. The pros and cons of our screening method are discussed.

PMID- 21193247
TI  - [Mortality due to influenza A (H1N1) virus: forensic experience and
      epidemiological implications].

PMID- 21193248
TI  - [Implementing a quality management system according to iso model in a
      Microbiology laboratory].

PMID- 21193249
TI  - Monoclonal antibodies. Basic features.
AB  - INTRODUCTION: Monoclonal antibodies are a powerful tool in laboratory diagnosis
      and are increasingly used in the treatment of several diseases. DEVELOPMENT:
      Antibody development and characterization has a long history and goes back to
      immunology itself. The present article provides a historical introduction to
      humoral immunity until the discovery of monoclonal antibodies and reviews
      concepts relating to the structure and function of antibodies, as well as to the
      generation of diversity, activation and maturation of B lymphocytes. The main
      techniques for producing monoclonal antibodies are outlined and some of their
      applications in human disease are described. CONCLUSIONS: Since their discovery,
      monoclonal antibodies have revolutionized the diagnosis and treatment of numerous
      diseases. The use of human and humanized monoclonal antibodies has markedly
      improved their tolerability. Current technology for manufacturing these
      antibodies allows new designs that may broaden their possible applications in
      medicine.

PMID- 21193250
TI  - Natalizumab for relapsing-remitting multiple sclerosis.
AB  - INTRODUCTION: Natalizumab is a monoclonal antibody that inhibits leukocyte
      migration across the blood-brain barrier and has been approved for the treatment
      of relapsing-remitting multiple sclerosis. OBJECTIVE: To provide a review and
      update of the pharmacological and therapeutic characteristics of natalizumab,
      with special emphasis on the most recently published data on the efficacy,
      effectiveness and safety of this drug. DEVELOPMENT: Several randomized clinical
      trials in patients with relapsing forms of multiple sclerosis have demonstrated
      that natalizumab substantially reduces clinical and radiological disease
      activity. Post hoc analysis of phase III clinical trials and the results of post
      approval observational studies indicate that natalizumab significantly increases
      the proportion of patients with complete clinical and radiological response and
      is effective in patients with highly active forms of multiple sclerosis and
      suboptimal response to other treatments. Like other monoclonal antibodies,
      natalizumab can cause hypersensitivity reactions, which are severe in 1% of
      patients. Other adverse effects are generally mild or infrequent. Nevertheless,
      several cases of progressive multifocal leukoencephalopathy have been detected in
      patients treated with natalizumab monotherapy. The risk of this severe
      complication seems to increase with the number of doses administered. CONCLUSION:
      Natalizumab has a favorable risk-benefit ratio in the treatment of relapsing 
      remitting multiple sclerosis. However, because of the potential risk of
      progressive multifocal leukoencephalopathy, patients must be carefully selected
      and specific protocols must be followed during the drug's administration.

PMID- 21193251
TI  - Anomalous behavior of pentacoordinate copper complexes of dimethylphenanthroline
      and derivatives of terpyridine ligands: Studies on DNA binding, cleavage and
      apoptotic activity.
AB  - Copper(II) complexes with substituted terpyridine ligands, namely
      [Cu(itpy)(dmp)](NO3)2 (1) and [Cu(ptpy)(dmp)](NO3)2 (2) have been synthesized and
      characterized. The interaction of the complexes with CT-DNA has been explored
      using spectroscopic techniques and viscosity. Complexes 1 and 2 bind in the
      grooves of DNA, interestingly 1 in the minor and 2 in the major groove. Both the
      complexes have been found to promote DNA cleavage; complex 1 through hydrolytic
      and 2 oxidative. Complexes 1 and 2 have been found to be cytotoxic and bring
      about apoptosis of human lung cancer cell line A549.

PMID- 21193252
TI  - Molecular modeling study and synthesis of quinazolinone-arylpiperazine
      derivatives as alpha1-adrenoreceptor antagonists.
AB  - Three series of new 2-[(4-substituted piperazin-1-yl) methyl]quinazolin-4(3H)
      ones 4a-c, Ethyl 6,7-dimethoxy-4-oxo-3-[2-(4-substituted piperazin-1
      yl)acetamido/propanamido]-3,4-dihydroquinazoline-2-carboxylates 9a-f and their 2
      methyl analogues 13a-l were designed and synthesized as promising alpha1
      adrenoceptor antagonists. The final compounds were evaluated for their in vivo
      hypotensive activity in normotensive cats. The most potent hypotensive
      quinazolinone derivatives 4b, 9e, 13i, 13j were further tested on isolated
      thoracic aortic rings of male Wister rats. All the tested compounds displayed
      alpha1-blocking activity with IC50 ranging from 0.2 to 0.4 mM less than prazosin.
      Furthermore, in the present work, molecular modeling study using Accelrys
      Discovery Studio 2.1 software was performed by mapping the synthesized compounds
      to the alpha1-adrenoceptor antagonist hypothesis in order to predict their
      mechanism of action. Compound 13j which has the best-fitting score displayed the
      highest in vivo and in vitro activity among the tested compounds.

PMID- 21193253
TI  - Analytical results and effective dose estimation of the operational Environmental
      Monitoring Program for the radioactive waste repository in Abadia de Goias from
      1998 to 2008.
AB  - This paper presents the results of the Environmental Monitoring Program for the
      Radioactive waste repository of Abadia de Goias, which was originated from the
      accident of Goiania, conducted by the Regional Center of Nuclear Sciences (CRCN
      CO) of the National Commission on Nuclear Energy (CNEN), from 1998 to 2008. The
      results are related to the determination of (137)Cs activity per unit of mass or
      volume of samples from surface water, ground water, depth sediments of the river,
      soil and vegetation, and also the air-kerma rate estimation for gamma exposure in
      the monitored site. In the phase of operational Environmental Monitoring Program,
      the values of the geometric mean and standard deviation obtained for (137)Cs
      activity per unit of mass or volume in the analyzed samples were (0.08 +/- 1.16)
      Bq.L(-1) for surface and underground water, (0.22 +/- 2.79) Bq.kg(-1) for soil,
      and (0.19 +/- 2.72) Bq.kg(-1) for sediment, and (0.19 +/- 2.30) Bq.kg(-1) for
      vegetation. These results were similar to the values of the pre-operational
      Environmental Monitoring Program. With these data, estimations for effective dose
      were evaluated for public individuals in the neighborhood of the waste
      repository, considering the main possible way of exposure of this population
      group. The annual effective dose obtained from the analysis of these results were
      lower than 0.3 mSv.y(-1), which is the limit established by CNEN for
      environmental impact in the public individuals indicating that the facility is
      operating safely, without any radiological impact to the surrounding environment.

PMID- 21193254
TI  - An overview of experimental results and dispersion modelling of nanoparticles in
      the wake of moving vehicles.
AB  - Understanding the transformation of nanoparticles emitted from vehicles is
      essential for developing appropriate methods for treating fine scale particle
      dynamics in dispersion models. This article provides an overview of significant
      research work relevant to modelling the dispersion of pollutants, especially
      nanoparticles, in the wake of vehicles. Literature on vehicle wakes and
      nanoparticle dispersion is reviewed, taking into account field measurements, wind
      tunnel experiments and mathematical approaches. Field measurements and modelling
      studies highlighted the very short time scales associated with nanoparticle
      transformations in the first stages after the emission. These transformations
      strongly interact with the flow and turbulence fields immediately behind the
      vehicle, hence the need of characterising in detail the mixing processes in the
      vehicle wake. Very few studies have analysed this interaction and more research
      is needed to build a basis for model development. A possible approach is proposed
      and areas of further investigation identified.

PMID- 21193255
TI  - Mandibular fractures related to the surgical extraction of impacted lower third
      molars: a report of 11 cases.

PMID- 21193256
TI  - Spontaneous migration of third molar following displacement to pterygomandibular
      fossa.

PMID- 21193258
TI  - Necrotising pneumonia due to Finegoldia magna.

PMID- 21193257
TI  - Computer-assisted designed and computer-assisted manufactured
      polyetheretherketone prosthesis for complex fronto-orbito-temporal defect.

PMID- 21193259
TI  - Early development of leaks in the CoreValve percutaneous aortic valve prosthesis:
      echocardiographic assessment.
AB  - The study investigated echocardiographic findings after 1 month in 22 patients
      who received a CoreValve prostheses to treat aortic valve stenosis. Particular
      attention was paid to the evaluation of valvular leaks and the left ventricular
      wall thickness. Echocardiograms were obtained prior to implantation, at discharge
      and 1 month later. The patients' mean age was 77 +/- 4 years. At discharge, 16
      patients (76%) had aortic regurgitation: 8 grade I and 8 grade II. At 1 month,
      only 13 (62%) presented with the condition: 10 grade I and 3 grade II, with 8
      patients (38%) demonstrating a reduction of at least one grade (P < .005). The
      septal thickness decreased (from 14.2 +/- 2 mm at baseline to 11 +/- 2.4 mm at 1
      month; P < .001), as did the posterior wall thickness (from 10.9 +/- 2.4 mm at
      baseline to 8.3 +/- 1.2 mm at 1 month; P < .001). In our patient series, the
      frequency and grade of residual aortic regurgitation after implantation of the
      CoreValve prosthesis decreased within 1 month, and favorable left ventricular
      remodeling was also observed.

PMID- 21193260
TI  - Performance of supraglottic airway devices and 12 month skill retention: a
      randomized controlled study with manikins.
AB  - PURPOSE: Airway management for successful ventilation by laypersons and
      inexperienced healthcare providers is difficult to achieve. Bag-valve mask (BVM)
      ventilation requires extensive training and is performed poorly. Supraglottic
      airway devices (SADs) have been successfully introduced to clinical resuscitation
      practice as an alternative. We evaluated recently introduced (i-gelTM and LMA
      SupremeTM) and established SADs (LMA-UniqueTM, LMA-ProSealTM) and BVM used by
      laypeople in training sessions on manikins. METHODS: In this randomized
      controlled study, 267 third-year medical students participated with informed
      consent and IRB approval. After brief standardized training, each participant
      applied all devices in a randomized order. Success of device application and
      ventilation was recorded. Without further training, skill retention was assessed
      in the same manner 12 months later. Outcome parameters were the number of
      application attempts, application time, tidal volume and gastric inflation rate
      recorded at successful attempts, and subjective ease-of-use rating by the
      participants. RESULTS: i-gelTM and LMA-SupremeTM were the most successful in the
      first attempt at both assessments and in the subjective ease-of-use rating. The
      shortest application time was found with BVM (8 +/- 5s in 2008 vs. 9 +/- 5s in
      2009) and i-gel (10 +/- 3s vs. 12 +/- 5s). Tidal volumes were disappointing with
      no device reaching 50% volume within the recommended range (0.4-0.6L). Gastric
      inflation rate was highest with BVM (18% vs. 20%) but significantly lower with
      all SADs (0.4-6%; p < 0.001 for 2008 and 2009). CONCLUSION: SADs showed clear
      advantages over BVM. Compared with LMA-UniqueTM and LMA-ProSealTM, i-gelTM and
      LMA-SupremeTM led to higher first-attempt success rates and a shorter application
      time.

PMID- 21193261
TI  - Outcome of expectant management of cervical intraepithelial neoplasia grade 2 in
      women followed for 12 months.
AB  - OBJECTIVE: To evaluate the outcome of CIN 2 diagnosed by colposcopy-directed
      biopsy in women followed without treatment for 12 months and to verify whether
      the regression and progression of this lesion are associated with the woman's age
      at diagnosis and age at first sexual intercourse. STUDY DESIGN: Women diagnosed
      with CIN 2 by biopsy and with previous cervical smear showing LSIL were included
      in this cohort study and followed up for one year with cervical smear and
      colposcopy every three months. The rates of progression, persistence and
      regression of the CIN 2 were evaluated. The Kruskal-Wallis test was used to
      analyze the woman's age at diagnosis, age at first sexual intercourse and
      interval since the first sexual intercourse according to the CIN 2 outcome,
      assuming a significance level of 5%. RESULTS: At the end of 12 months of follow
      up the CIN 2 regression rate was 74% (31/42), progression rate to CIN 3 was 24%
      (10/42) and in one case CIN 2 persisted (2%). Among women who had regression,
      this event was detected in the first six months of follow-up in 26 of the 31
      cases. There was no statistically significant association between the evolution
      of CIN 2 and the woman's age at diagnosis, age at first sexual intercourse and
      interval since first sexual intercourse. Women whose lesions were restricted to
      one quadrant were more likely to have CIN 2 regression at three-month follow-up
      compared with women with a lesion extending to one or more quadrants (OR: 6.50;
      95% CI: 1.20-35.23). CONCLUSIONS: The results of this study indicate that the
      majority of CIN 2 diagnosed by biopsy in women with previous Pap smear showing
      LSIL will regress in 12 months and therefore an expectant approach could be
      considered in these cases, not only for young women. Nevertheless these findings
      are not conclusive, and larger studies are required in order to certify when it
      is safe to adopt expectant management for CIN 2.

PMID- 21193262
TI  - Anti-Helicobacter pylori antibodies in cervical mucus: a new cause of
      infertility.
AB  - OBJECTIVE: The aims of our study were to determine on the one hand a correlation
      between the presence of anti-Helicobacter pylori (anti-H. pylori) IgG antibodies
      in serum and cervical mucus of women with idiopathic infertility, and on the
      other hand the effect of these antibodies on cervical mucus quality, in
      particular related to the ability of spermatozoa to penetrate it. STUDY DESIGN:
      We analysed anti-H. pylori IgG antibodies in the serum and cervical mucus of 67
      patients diagnosed with idiopathic infertility using the Quanta Lite H. pylori
      IgG test. The penetration of normal sperm, in 15 cervical mucus samples positive
      for anti-H. pylori antibodies and in 15 negative samples, was assessed using the
      simplified slide test. RESULTS: A significant positive correlation emerged
      between anti-H. pylori IgG antibody concentrations in the serum and in the
      cervical mucus (r=0.9275; p<0.00001). In the 15 anti-H. pylori IgG mucus-positive
      samples the slide test showed abnormal penetration by the spermatozoa.
      CONCLUSIONS: Our study demonstrated that the presence of anti-H. pylori antibody
      in the cervical mucus can be involved in female infertility, interfering with
      sperm progression. Considering the close correlation found between serum and
      cervical mucus anti-H. pylori antibody titres, measuring serum antibodies could
      become an additional test, in particular in couples with unexplained infertility.

PMID- 21193263
TI  - Oxidation of inorganic contaminants by ferrates (VI, V, and IV)--kinetics and
      mechanisms: a review.
AB  - Inorganic contaminants are found in water, wastewaters, and industrial effluents
      and their oxidation using iron based oxidants is of great interest because such
      oxidants possess multi-functional properties and are environmentally benign. This
      review makes a critical assessment of the kinetics and mechanisms of oxidation
      reactions by ferrates (Fe(VI)O(4)(2-), Fe(V)O(4)(3-), and Fe(IV)). The rate
      constants (k, M(-1) s(-1)) for a series of inorganic compounds by ferrates are
      correlated with thermodynamic oxidation potentials. Correlations agree with the
      mechanisms of oxidation involving both one-electron and two-electron transfer
      processes to yield intermediates and products of the reactions. Case studies are
      presented which demonstrate that inorganic contaminants can be degraded in
      seconds to minutes by ferrate(VI) with the formation of non-toxic products.

PMID- 21193264
TI  - Effect of pulp mill sludge on soil characteristics, microbial community and
      vegetal production of Lolium Perenne.
AB  - The effect of pulp mill sludge addition (10-30 Mg/ha) to soil derived from
      volcanic ash (Andisol) on soil characteristics, microbial community and Lolium
      perenne L. cv quartet. biomass production was evaluated in field assays. Soil
      without sludge was used as a control treatment. The sludge addition improved the
      chemical properties of the soil. Organic matter and phosphorous content increased
      in the soil with increasing amounts of sludge, obtaining 35% more organic matter
      content with the application of 30 Mg/ha than the control soil. The phosphorous
      was accumulated into the soil after the end of cultivation improving the
      phosphorous pool in the soil. When 30 Mg/ha sludge was added to the soil, a
      biomass of Lolium perenne, was 60% more than the control soil at the end of the
      experiment. The analysis of soil microbial community showed that the application
      of sludge did not modify greatly the microbial community of fungi and bacteria
      even when high doses were applied.

PMID- 21193265
TI  - Assessing farming eco-efficiency: a Data Envelopment Analysis approach.
AB  - This paper assesses farming eco-efficiency using Data Envelopment Analysis (DEA)
      techniques. Eco-efficiency scores at both farm and environmental pressure
      specific levels are computed for a sample of Spanish farmers operating in the
      rain-fed agricultural system of Campos County. The determinants of eco-efficiency
      are then studied using truncated regression and bootstrapping techniques. We
      contribute to previous literature in this field of research by including
      information on slacks in the assessment of the potential environmental pressure
      reductions in a DEA framework. Our results reveal that farmers are quite eco
      inefficient, with very few differences emerging among specific environmental
      pressures. Moreover, eco-inefficiency is closely related to technical
      inefficiencies in the management of inputs. Regarding the determinants of eco
      efficiency, farmers benefiting from agri-environmental programs as well as those
      with university education are found to be more eco-efficient. Concerning the
      policy implications of these results, public expenditure in agricultural
      extension and farmer training could be of some help to promote integration
      between farming and the environment. Furthermore, Common Agricultural Policy agri
      environmental programs are an effective policy to improve eco-efficiency,
      although some doubts arise regarding their cost-benefit balance.

PMID- 21193266
TI  - Photocatalytic oxidation of ciprofloxacin under simulated sunlight.
AB  - Ciprofloxacin (CIP) is a famous synthetic chemotherapeutic antibiotic. It is
      widely found either in water or wastewater. In this study ciprofloxacin was
      photocatalytically degraded using commercial anatase titanium dioxide (TiO(2))
      under simulated sunlight. The rate of reaction was found to be affected by pH,
      TiO(2) concentration and antibiotic concentration. The best reaction rate was
      obtained in natural ciprofloxacin pH (5.8) and 1000 mg/L TiO(2). More titania
      concentration was found to reduce the reaction rate because of the limitation in
      light transmittance. From kinetic studies, the reaction was proved to proceed
      through adsorption step then photooxidation and obeys pseudo-first order
      kinetics.

PMID- 21193267
TI  - WITHDRAWN: A MVSA approach to mine information from APT data.
AB  - This article has been withdrawn at the request of the author. 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- 21193268
TI  - Optimized conditions for imaging the effects of bonding charge density in
      electron microscopy.
AB  - We report on the observability of valence bonding effects in aberration-corrected
      high resolution electron microscopy (HREM) images along the [010] projection of
      the mineral Forsterite (Mg2SiO4). We have also performed exit wave restorations
      using simulated noisy images and have determined that both the intensities of
      individual images and the modulus of the restored complex exit wave are most
      sensitive to bonding effects at a level of 25% for moderately thick samples of 20
      25 nm. This relatively large thickness is due to dynamical amplification of
      bonding contrast arising from partial de-channeling of 1s states. Simulations
      also suggest that bonding contrast is similarly high for an un-corrected
      conventional electron microscope, implying an experimental limitation of signal
      to noise ratio rather than spatial resolution.

PMID- 21193269
TI  - Effect of grape seed extract on oxidative, color and sensory stability of a pre
      cooked, frozen, re-heated beef sausage model system.
AB  - To compare grape seed extract (GSE) to common antioxidants in a pre-cooked,
      frozen, stored meat model system sausage was manufactured from lean beef (70%),
      pork fat (28%), and salt (2%). Antioxidants added for comparison with control
      included grapeseed extract (100, 300, and 500 ppm), ascorbic acid (AA, 100 ppm of
      fat) and propyl gallate (PG, 100 ppm of fat). Product was formed into rolls,
      frozen, sliced into patties, cooked on a flat griddle to 70  degrees C,
      overwrapped in PVC, then frozen at - 18  degrees C for 4 months. GSE- and PG
      containing samples retained their fresh cooked beef odor and flavor longer (p <
      0.05) than controls during storage. Rancid odor and flavor scores of GSE
      containing samples were lower (p < 0.05) than those of controls after 4months of
      storage. The L* value of all samples increased (p<0.05) during storage.
      Thiobarbituric acid reactive substances (TBARS) of the control and AA-containing
      samples increased (p < 0.05); those of GSE-containing samples did not change
      significantly (p > 0.05) over the storage period.

PMID- 21193270
TI  - Genetic moderators and psychiatric mediators of the link between sexual abuse and
      alcohol dependence.
AB  - BACKGROUND/OBJECTIVE: This study used a case-control female sample to test
      psychiatric mediators and genetic moderators of the effect of sexual abuse on
      later alcohol dependence. The study also tested differences between alcohol
      dependent women with or without a history of sexual abuse on variables that might
      affect treatment planning. METHODS: A case-control design compared 192 treatment
      seeking alcohol dependent women with 177 healthy population controls. All
      participants were assessed for alcohol-related behaviors, sexual abuse history,
      psychiatric problems, and personality functioning. Markers were genotyped in the
      CRHR1, MAO-A and OPRM1 genes. RESULTS: The association of sexual abuse with
      alcohol dependence was limited to the most severe category of sexual abuse
      involving anal or vaginal penetration. Of the five psychiatric disorders tested,
      anxiety, anorexia nervosa, and bulimia met criteria as potential mediators of the
      abuse-alcohol dependence association. Severe sexual abuse continued to have an
      independent effect on alcohol dependence status even after accounting for these
      potential mediators. None of the candidate genetic markers moderated the
      association between sexual abuse and alcohol dependence. Of alcohol dependent
      participants, those with a history of severe abuse rated higher on alcoholism
      severity, and psychiatric comorbidities. CONCLUSION: Sexual abuse is associated
      with later alcohol problems directly as well as through its effect on psychiatric
      problems. Treatment-seeking alcohol dependent women with a history of abuse have
      distinct features as compared to other alcohol dependent women.

PMID- 21193271
TI  - Measuring costs of alcohol harm to others: a review of the literature.
AB  - INTRODUCTION: People other than the drinker experience harmful consequences from
      alcohol misuse, accounting for part of the economic burden to society. Little has
      been done on costing harm to others. AIMS:  METHOD: A literature review was
      undertaken of various databases, government publications, dissertations,
      conference papers and reference materials. Publications were included for
      analysis if they reported costs on alcohol harm to others. Methodological
      adequacy of costing studies was assessed using a checklist modified from the
      Drummond 10-point checklist. RESULTS: In total, 25 publications including costs
      on alcohol harm to others were reviewed. Fetal alcohol syndrome (FAS) was the
      harm to others most frequently cost. The cost-of-illness (COI) framework was used
      in 24 of the publications, while 1 employed a cost-benefit analysis (CBA) serving
      as starting point for further studies estimating intangible costs (e.g. victim's
      quality-of-life (QoL) loss). Indirect costs (e.g. victim's lost productivity)
      were quantified most frequently with the human capital approach. The majority of
      publications critically assessed on costing received an average quality score
      (17/25). CONCLUSION: Few studies have reported costs on the magnitude from harm
      to people other than the drinker, therefore the overall economic burden of risky
      alcohol consumption across countries is underestimated. This review may be
      considered a starting point for future research on costing alcohol harm to
      others.

PMID- 21193272
TI  - Socio-demographic and drug use factors associated with HIV-1 recombinants and
      dual infections in Northern Thai drug users: associations of risk with genetic
      complexity.
AB  - BACKGROUND: Dual infection with diverse HIV strains can foster the emergence of
      recombinants. The resulting increase in viral genetic diversity is a major
      challenge for vaccine development HIV treatment. In this study we aim to
      investigate the socio demographic factors associated with an increasing level of
      genetic diversity among HIV strains in a population of drug-users in Northern
      Thailand. METHODS: From 1999 through 2000, 2231 volunteers were enrolled in the
      Opiate-Users Research in Chiang Mai, Thailand. HIV subtype analysis was conducted
      among those HIV-1 seropositive (n=347) using a multi-region hybridization assay.
      Social and demographic variables were assessed using a structured questionnaire.
      RESULTS: Overall, 336/347 (96.8%) of the samples could be typed. 81.8% were
      CRF01_AE, 3.9% were subtype B, 9.2% were recombinants (mostly between CRF01_AE
      and B) and 5.1% were dual infections. Dual infections were more frequent among
      those with a lower education level (AOR: 5.2; 95% CI 1.4-20.3), those who have
      initiated injecting in the last 3 years (AOR: 3.9; 95% CI 1.1-14.6), and those
      reporting frequent needle sharing in the last 3 months (AOR: 7.0; 95% CI 1.5
      34.1). Both recombinant strains and dual infection were more frequent among those
      reporting frequent needle sharing in the last 3 months (AOR: 5.3; 95% CI 1.6
      17.1). CONCLUSION: To limit the expanding complexity of HIV-1 strains, early
      intervention should be aimed at reduction in needle sharing, especially among new
      intravenous drug users.

PMID- 21193273
TI  - The association between frontal-striatal connectivity and sensorimotor control in
      cocaine users.
AB  - BACKGROUND: In addition to cognitive and emotional processing dysfunction,
      chronic cocaine users are also impaired at simple sensorimotor tasks. Many
      diseases characterized by compulsive movements, repetitive actions, impaired
      attention and planning are associated with dysfunction in frontal-striatal
      circuits. The aim of this study was to determine whether cocaine users had
      impaired frontal-striatal connectivity during a simple movement task and whether
      this was associated with sensorimotor impairment. METHODS: Functional MRI data
      were collected from 14 non-treatment seeking cocaine users and 15 healthy
      controls as they performed a finger-tapping task. Functional coupling was
      quantified by correlating the timecourses of each pair of anatomically connected
      regions of interest. Behavioral performance was correlated with all functional
      coupling coefficients. RESULTS: In controls there was a significant relationship
      between the primary motor cortex and the supplementary motor area (SMA), as well
      as the SMA and the dorsal striatum during ongoing movement. Cocaine users
      exhibited weaker fronto-striatal coupling than controls, while the cortical
      cortical coupling was intact. Coupling strength between the SMA and the caudate
      was negatively correlated with reaction time in the users. CONCLUSIONS: The
      observation that cocaine users have impaired cortical-striatal connectivity
      during simple motor performance, suggests that these individuals may have a
      fundamental deficit in information processing that influences more complex
      cognitive processes.

PMID- 21193274
TI  - Detection of amitriptyline, nortriptyline and bromazepam in liver, CSF and hair
      in the homicidal poisoning of a one-month-old girl autopsied 8 months after
      death.
AB  - We reported on the death by poisoning of a one-month-old baby that had followed
      the death of one of her sister (due to cyamemazine overdose). Exhumation of the
      corpse was done 8 months after burial and revealed the presence of amitriptyline.
      Parent drug and its metabolite were analysed by HPLC-MS/MS in positive ionisation
      mode on a C(18) analytical column using a gradient of acetonitrile and 2mM
      formate buffer at pH=3. Quantification is based on the main ion m/z=233, the
      common product ion of nortriptyline (MH(+), m/z 264), amitriptyline (MH(+), m/z
      278) and nortriptyline D3 used as internal standard (MH(+), m/z 267).
      Amitriptyline and nortriptyline in the liver were measured at a concentration of
      29.8 and 3.6 MUg/g, respectively. Hair analyses revealed the presence of
      amitriptyline and nortriptyline at concentrations of 1811 and 43 pg/mg,
      respectively, while complementary analyses showed the presence of bromazepam in
      the hair at a concentration of 740 pg/mg, thus documenting previous
      administrations. The mother confessed later having used the drinkable form of the
      pharmaceutical LAROXYL((r)) by pouring the content of a 20 ml bottle (at 40
      mg/ml) into the feeding-bottle of her child. The milk was sweet but still bitter
      and following the testimony of a close relative, the whole family helped to feed
      the crying baby.

PMID- 21193275
TI  - Pan-susceptible Proteus mirabilis septicemia in a patient multicolonized by pan
      resistant bacteria.

PMID- 21193276
TI  - Combination of vascular endothelial growth factor antisense oligonucleotide
      therapy and radiotherapy increases the curative effects against maxillofacial VX2
      tumors in rabbits.
AB  - PURPOSE: To study the effects of combination of vascular endothelial growth
      factor (VEGF) antisense oligonucleotide therapy and radiotherapy on maxillofacial
      VX2 tumors in rabbits. METHODS: We used 24 New Zealand white rabbits as a model
      to induce maxillofacial VX2 tumor. The rabbits were randomly divided into the
      following 4 groups: radiotherapy group (group A), treated with 16 Gy of
      radiotherapy; VEGF antisense oligonucleotide treatment group (group B), treated
      with an injection of 150 MUg of VEGF antisense oligonucleotide into the local
      tumor; VEGF antisense oligonucleotide combined with radiotherapy group (group C),
      treated with an injection of 150 MUg of VEGF antisense oligonucleotide into the
      local tumor immediately after 16 Gy of radiotherapy; and control group (group D),
      treated with an injection of 300 MUl 5% aqueous glucose solution into the local
      tumor. On days 3 and 14 after treatment, dynamic contrast-enhanced magnetic
      resonance imaging (DCE-MRI) was performed to calculate maximal enhancement ratio
      (MER), slope of enhancement (SLE), and tumor volume change. Rabbits were killed
      on day 14 to obtain samples for pathological examination and immunohistochemical
      staining for VEGF. RESULTS: In group C, tumor volume was significantly reduced on
      day 14 after treatment, and the difference was statistically different as
      compared to that before treatment, on day 3 after treatment and other groups (P <
      0.01). Values of both MER and SLE after treatment were significantly lower than
      the values before treatment (P < 0.05). Pathological specimen revealed tumor cell
      edema, bleeding, necrosis, vascular wall thickening and occlusion, and decreased
      VEGF expression. The immunohistochemical score (IHS) of group C was significantly
      different from groups A and D respectively (P < 0.05). CONCLUSION: Injecting the
      tumor with VEGF antisense oligonucleotide immediately after radiotherapy can
      enhance the curative effect on rabbit maxillofacial VX2 tumor, and DCE-MRI can
      serve as a reliable technique for in vivo monitoring.

PMID- 21193277
TI  - Assessing the degree of collinearity among the lesion features of the MRI BI-RADS
      lexicon.
AB  - PURPOSE: To retrospectively assess collinearity among lesion feature of the MRI
      BI-RADS lexicon. Collinearity denotes a situation in which two or more
      (independent) variables are correlated to some degree, thus partly conveying the
      same information. Collinearity may cause problems in the interpretation of
      logistic regression models. MATERIALS AND METHODS: We analysed the BI-RADS
      features of 351 lesions in 325 consecutive patients. Patients with biopsy proven
      breast disease or treated with chemotherapy were excluded. All lesion features
      were dichotomised into "present" or "not present". Correlation matrices were
      generated for mass and non-mass lesions separately, focus lesions were omitted.
      The phi coefficient was used as measure for correlation. RESULTS: There were 253
      mass (175 malignant, 78 benign), 66 non-mass (21 malignant, 45 benign) and 32
      focus (5 malignant, 27 benign) lesions among the study population. The strongest
      inter-subgroup correlations among mass lesion features were: slow initial
      enhancement with persistent kinetics, phi=0.64 (0.56-0.71), rapid initial
      enhancement with washout kinetics, phi=0.52 (0.43-0.61) and rapid initial
      enhancement with persistent kinetics, phi=-0.43 (-0.53 to -0.32). The strongest
      inter-subgroup correlation among non-mass lesion features were: rapid initial
      enhancement with washout kinetics, phi=0.51 (0.30-0.67), slow initial enhancement
      with persistent kinetics, phi=0.43 (0.21-0.61) and rapid initial enhancement with
      persistent kinetics, phi=-0.41 (-0.18 to -0.60). CONCLUSION: There is a
      noticeable overlap of information, especially between kinetic features and
      initial enhancement types for both, mass and non-mass lesions. This should be
      considered when generating logistic regression models with the MRI BI-RADS lesion
      features.

PMID- 21193278
TI  - CT fluoroscopy-guided cutting needle biopsy of focal pure ground-glass opacity
      lung lesions: diagnostic yield in 83 lesions.
AB  - OBJECTIVE: The objective of our study was to retrospectively determine the
      diagnostic yield of CT fluoroscopy-guided cutting needle biopsy of focal pure
      ground-glass opacity lung lesions. MATERIALS AND METHODS: Biopsies were performed
      using 20-G coaxial cutting needles for 83 focal pure ground-glass opacity lung
      lesions (mean lesion size, 12.1mm). After excluding the lesions for which biopsy
      specimens were unobtainable and final diagnoses were undetermined, the diagnostic
      yield, including sensitivity and specificity for a diagnosis of malignancy and
      accuracy, was calculated. The lesions were then divided into 2 groups: the
      diagnostic failure group, comprising lesions with false-negative results and for
      which a biopsy specimen was unobtainable; and the diagnostic success group,
      comprising lesions with true-negative results and true-positive results. Various
      variables were compared between the 2 groups by univariate analysis. RESULTS:
      Biopsy specimens were obtained from 82 lesions, while specimens could not be
      obtained from 1 lesion. Final diagnosis was undetermined in 16 lesions. The
      sensitivity and specificity for a diagnosis of malignancy were 95% (58/61) and
      100% (5/5), respectively. Diagnostic accuracy was 95% (63/66). The 4 lesions in
      diagnostic failure group were smaller, deeper, and more likely to be located in
      the lower lobe and further, for those lesions, number of specimens obtained was
      smaller, compared with 63 lesions in diagnostic success group. However, none of
      the differences were statistically significant. CONCLUSION: CT fluoroscopy-guided
      cutting needle biopsy provided high diagnostic yield for focal pure ground-glass
      opacity lung lesions.

PMID- 21193279
TI  - A multilocus sequence analysis of Xanthomonas campestris reveals a complex
      structure within crucifer-attacking pathovars of this species.
AB  - Previous classification of Xanthomonas campestris has defined six pathovars
      (aberrans, armoraciae, barbareae, campestris, incanae, and raphani) that cause
      diseases on cruciferous plants. However, pathogenicity assays with a range of
      strains and different hosts identifies only three types of symptom: black rot,
      leaf spot and bacterial blight. These findings raise the question of the genetic
      relatedness between strains assigned to different pathovars or symptom
      phenotypes. Here we have addressed this issue by multilocus sequence analysis of
      42 strains. The X. campestris species was polymorphic at the 8 loci analysed and
      had a high genetic diversity; 23 sequence types were identified of which 16 were
      unique. All strains that induce black rot (pathovars aberrans and campestris)
      were genetically close but split in two groups. Only three clonal complexes were
      found, all within pathovar campestris. The assignment of the genome-sequenced
      strain 756C to pathovar raphani suggested from disease symptoms was confirmed,
      although this group of strains was particularly polymorphic. Strains belonging to
      pathovars barbareae and incanae were closely related, but distinct from pathovar
      campestris. There is evidence of genetic exchanges of housekeeping genes within
      this species as deduced from a clear incongruence between individual gene
      phylogenies and from network structures from SplitsTree analysis. Overall this
      study showed that the high genetic diversity derived equally from recombination
      and point mutation accumulation. However, X. campestris remains a species with a
      clonal evolution driven by a differential adaptation to cruciferous hosts.

PMID- 21193280
TI  - Strategies for the identification, control and determination of genotoxic
      impurities in drug substances: a pharmaceutical industry perspective.
AB  - Regulations alarmed the control of genotoxic impurities in drug substances at
      lower level based on the threshold of toxicological concern and daily dose. This
      review explores the details of various regulations and guidances, toxicology
      assessment, identification of structural alerts, synthetic origins, different
      synthetic approaches for elimination or control, various analytical determination
      strategies and pharmaceutical industry concern towards genotoxic impurities.

PMID- 21193281
TI  - Analyzing differences between psychotherapy groups and social support groups for
      breast cancer patients: development of an assessment method using video
      recordings.
AB  - OBJECTIVE: When comparing the efficacy of different interventions for cancer
      patients, there should be certainty that these types are sufficiently different
      in the way they are actually presented. The aim of the present study is to
      develop a method for assessing differences between the content of social support
      groups and experiential-existential therapy groups. METHODS: Independent and
      blind raters assessed video fragments of both intervention types, using a self
      developed checklist of five questions. This checklist was first evaluated by a
      group of experts for appropriateness, importance, and rateability. RESULTS: Three
      out of the five questions were selected on the basis of these experts' evaluation
      and on inter-rater reliability. The scores on these questions were used to
      evaluate five social support groups and six experiential-existential therapy
      groups for breast cancer patients. According to the independent and blind raters
      the content of the two intervention forms appeared to be significantly different.
      CONCLUSION: The assessment method we developed appeared reliable and valid.
      PRACTICE IMPLICATIONS: Our assessment method is feasible as a check to compare
      the content of psycho-oncological interventions and can be easily adjusted into a
      test for other intervention types.

PMID- 21193282
TI  - Prescription and over-the-counter drug treatment admissions to the California
      public treatment system.
AB  - Prescription and over-the-counter (OTC) drug abuse has become a focal point of
      public health policy, prevention, and control efforts. Adolescents represent one
      of the fastest growing segments of the general population abusing prescription
      and OTC drugs as represented by national surveys. This article reports on
      treatment admission data to the California addiction public system for
      prescription and OTC drugs among two age subgroups: adolescents 12-17 years and
      adults 18 years and older. Of the 6,841 admissions for primary abuse of
      prescription and OTC drugs in California (during 2006-2007), most adolescent
      admissions (12-17) were for stimulant prescription and OTC drugs (45.3% and
      32.1%, respectively), whereas opioid prescription drugs (88.9%) were most common
      for adults 18 years and older. Differences in psychosocial, treatment, and
      substance use characteristics between these two age subgroups are described.
      Results from this study offer useful treatment admission information about
      prescription and OTC drug abuse within the California public addiction treatment
      system.

PMID- 21193283
TI  - Readiness to change and risk drinking women.
AB  - The predictive value of the Readiness to Change Questionnaire (RTCQ) for
      subsequent drinking was evaluated in 499 women. These women had medical problems
      potentially exacerbated by alcohol use and were enrolled in an intervention
      study. Correlates and predictors of stage of change were analyzed. Results
      indicated that the categorical application of the RTCQ did not predict drinking
      in the 6-12 months after enrollment. Preliminary findings support rescoring the
      RTCQ into a continuous measure. Following this conversion, situational risks
      factors for drinking were examined as potential mediators of readiness to change
      (RTC). Heightened risk for alcohol consumption during argument or boredom was
      found to attenuate the association between one's RTC and later drinking. Finally,
      medical condition moderated the association of RTC on later drinking; women with
      diabetes, infertility, or osteoporosis drank the most in the contemplation stage.
      In contrast, hypertensive women drank more when action oriented to change. The
      implications for treating risk drinking in women are discussed.

PMID- 21193285
TI  - Colon carcinoma--classification into right and left sided cancer or according to
      colonic subsite?--Analysis of 29,568 patients.
AB  - BACKGROUND: It is common to distinguish between right and left colon cancer (RCC
      and LCC). But, little is known about the influence of its exact location on the
      tumor stage and characteristics when considering the colonic subsite within the
      right or left colon. METHODS: During a five-year period, 29,568 consecutive
      patients were evaluated by data from the German multi-centered observational
      study "Colon/Rectal Carcinoma". Patients were split into 7 groups, each group
      representing a colonic subsite. They were compared regarding demographic factors,
      tumor stage, metastatic spread and histopathological characteristics. RESULTS:
      Analysis of tumor differentiation and histological subtype revealed a linear
      correlation to the ileocecal valve, supporting the right and left side
      classification model. However, cancers arising from the RCC's cecum (52.3%) and
      LCC's splenic flexure (51.0%) showed the highest proportion of UICC stage III/IV
      tumors and lymphatic invasion, whereas the RCC's ascending colon (46.5%) and
      LCC's descending (44.7%) showed the lowest, which supports a more complex
      classification system, breaking down the right and left sides into colonic
      subsites. CONCLUSIONS: Age, tumor grade and histological subtype support the
      right and left side classification model. However, gender, UICC stage, metastatic
      spread, T and N status, and lymphatic invasion correlated with a specific colonic
      subsite, irrespective of the side. The classification of RCC or LCC provides a
      general understanding of the tumor, but identification of the colonic subsite
      provides additional prognostic information. This study shows that the standard
      right and left side classification model may be insufficient.

PMID- 21193284
TI  - College alcohol citations result in modest reductions in student drinking.
AB  - College students who are cited for violating campus alcohol policy are often
      fined or sanctioned to complete an intervention or public service. Although some
      interventions have been found efficacious for mandated students, it is possible
      that being cited for an alcohol-related incident alone may be sufficient to
      reduce alcohol consumption. The purpose of this study was to investigate the
      course of alcohol consumption patterns following a citation for an alcohol policy
      violation. Participants were college students (N = 445) who received a citation
      for a campus alcohol policy violation at a small northeastern liberal arts
      college. Participants completed a Timeline Follow-Back indicating their daily
      alcohol use 2 weeks prior to the citation through 2 weeks after the citation.
      Results indicated that participants decreased their alcohol use following a
      citation event. However, the reduction in alcohol consumption was modest,
      suggesting that the citation event itself has a very temporary influence on the
      drinking of college students. Additional research is needed to reconcile these
      findings with those from other studies that found a more meaningful citation
      effect.

PMID- 21193286
TI  - Node perturbation learning without noiseless baseline.
AB  - Node perturbation learning is a stochastic gradient descent method for neural
      networks. It estimates the gradient by comparing an evaluation of the perturbed
      output and the unperturbed output performance, which we call the baseline. Node
      perturbation learning has primarily been investigated without taking noise on the
      baseline into consideration. In real biological systems, however, neural
      activities are intrinsically noisy, and hence, the baseline is likely
      contaminated with the noise. In this paper, we propose an alternative learning
      method that does not require such a noiseless baseline. Our method uses a "second
      perturbation", which is calculated with different noise than the first
      perturbation. By comparing the evaluation of the outcomes with the first
      perturbation and with the second perturbation, the network weights are updated.
      We reveal that the learning speed showed only a linear decrease with the variance
      of the second perturbation. Moreover, using the second perturbation can lead to a
      decrease in residual error compared to the case of using the noiseless baseline.

PMID- 21193287
TI  - A randomized clinical controlled study comparing the effect of modified manual
      edema mobilization treatment with traditional edema technique in patients with a
      fracture of the distal radius.
AB  - STUDY DESIGN: Randomized controlled clinical trial. INTRODUCTION: Manual edema
      mobilization (MEM) is a method of edema reduction based on the lymphatic system's
      ability to drain and resolve subacute edema. PURPOSE OF THE STUDY: To investigate
      the effect of a modified MEM approach and compare it with a traditional edema
      technique in patients with subacute hand/arm edema after a distal radius
      fracture. METHOD: The patients were randomized into one of two treatment groups:
      a group that received traditional edema treatment and a group that received a
      modified MEM treatment. All patients were examined for edema, active range of
      motion (AROM), pain, and activities of daily living (ADL). The number of edema
      sessions and the number of all sessions were counted. RESULT: No statistically
      significant changes were observed in edema reduction, AROM, pain, and ADL at six
      and nine weeks between the treatment groups. A statistically significant
      improvement was observed in ADL after three weeks after inclusion (p=0.03) in the
      modified MEM group compared with the control group. Furthermore, fewer edema
      treatment sessions were needed (p=0.03) in the modified MEM group. At six weeks,
      we observed a difference between the two groups' needs for further edema
      treatment (p=0.04). CONCLUSION: Neither the traditional nor the modified MEM
      treatment program was superior in terms of edema reduction, although the modified
      MEM resulted in fewer sessions to decrease subacute hand/arm edema compared with
      using traditional edema reduction techniques in patients after distal radius
      fracture. LEVEL OF EVIDENCE: 1.

PMID- 21193288
TI  - Blocking of IL-6 suppresses experimental autoimmune myasthenia gravis.
AB  - Suppressive regulatory T cells (Treg) and pathogenic T helper 17 (Th17) cells are
      two lymphocyte subsets with opposing activities in autoimmune diseases. The
      proinflammatory cytokine IL-6 is a potent factor in switching immune responses in
      vivo from the induction of Treg to pathogenic Th17 cells. We studied the Treg and
      Th17 cell compartments in experimental autoimmune myasthenia gravis (EAMG) and
      healthy control rats in order to assess whether the equilibrium between Treg and
      Th17 cells is perturbed in the disease. We found that Th17 cell-related genes are
      upregulated and Treg-related genes are downregulated in EAMG. The shift in favor
      of Th17 cells in EAMG could be reversed by antibodies to IL-6. Administration of
      anti-IL-6 antibodies to myasthenic rats suppressed EAMG when treatment started at
      the acute or at the chronic phase of disease. Suppression of EAMG by anti-IL-6
      antibodies was accompanied by a decrease in the overall rat anti-AChR antibody
      titer and by a reduced number of B cells as compared with control treatment.
      Administration of anti-IL-6 antibodies led to down-regulation of several Th17
      related genes including IL-17, IL-17R, IL-23R and IL-21 but did not affect the
      number of Treg cells in the lymph nodes. These data identify IL-6 as an important
      target for modulation of autoimmune responses.

PMID- 21193289
TI  - The effectiveness of an aquarobic exercise program for patients with
      osteoarthritis.
AB  - Aquarobics, a combination of the words aqua and aerobics, is based on the idea
      that much more energy is consumed during exercise when resisting water rather
      than air. The aquarobic exercise program is composed of patient education and
      aquarobic exercise. The program was effective in enhancing self-efficacy,
      decreasing pain, and improving depression levels, body weight, and blood lipid
      levels in patients with osteoarthritis. Therefore, this program can be widely
      used in a community setting for the management of osteoarthritis.

PMID- 21193290
TI  - A pilot study to examine relationships among external counterpulsation, cardiac
      output, functional capacity, and quality of life.
AB  - This study examined the relationships among external counterpulsation (a
      noninvasive treatment for angina), cardiac output, functional limitations, and
      quality of life. Patients significantly improved their distance walked from the
      beginning to the end of the external counterpulsation program yet did not
      perceive differences in angina or quality of life.

PMID- 21193291
TI  - Commentary on an analysis of the existing resources in relation to education and
      treatment of diabetes in four European Countries: Estonia, Finland, Ireland, and
      Lithuania.

PMID- 21193293
TI  - Perilipin polymorphism interacts with saturated fat and carbohydrates to modulate
      insulin resistance.
AB  - BACKGROUND AND AIMS: Macronutrient intakes and genetic variants have been shown
      to interact to alter insulin resistance, but replications of gene-nutrient
      interactions across independent populations are rare, despite their critical
      importance in establishing credibility. We aimed to investigate a previously
      demonstrated saturated fat and carbohydrate interaction for insulin resistance
      for perilipin (PLIN1), a regulator of adipocyte metabolism. METHODS AND RESULTS:
      We investigated the previously shown interaction for PLIN1 11482G > A (rs894160)
      on insulin resistance in US men (n = 462) and women (n = 508) (mean +/- SD, 49 +/
      16 years). In multivariable linear regression models, we found an interaction (P
      < 0.05) between the ratio of saturated fat to carbohydrate intake as a continuous
      variable and PLIN1 11482G > A for HOMA-IR (homeostasis model assessment of
      insulin resistance) in women. For carriers of the minor allele but not for non
      carriers, as the ratio of saturated fat to carbohydrate intake increased,
      predicted HOMA-IR increased (P = 0.002). By dichotomizing the ratio of saturated
      fat to carbohydrate intake into high and low, we found significant interaction
      terms for insulin and HOMA-IR (P < 0.05). When the ratio of saturated fat to
      carbohydrate was high, insulin and HOMA-IR were higher in minor allele carriers
      (P = 0.004 and P = 0.003, respectively), but did not differ when the ratio was
      low. Similar patterns or trends were observed when saturated fat and carbohydrate
      were dichotomized into high and low as individual macronutrients. CONCLUSIONS:
      Replication of the previously reported interaction between macronutrient intakes
      and PLIN1 genotype for insulin resistance reinforces the potential usefulness of
      applying genotype information in the dietary management of insulin resistance.

PMID- 21193295
TI  - Effect of weight loss on inflammation in patients with mild obstructive sleep
      apnea.
AB  - BACKGROUND AND AIMS: Inflammation may be one mediating mechanism for
      cardiovascular diseases in obstructive sleep apnea (OSA). However, little is
      known about subclinical inflammation or the effect of lifestyle intervention on
      inflammation in early stages of OSA. The aim of this substudy of an existing
      randomized controlled trial, with post hoc analyses, was to determine the impact
      of lifestyle changes aimed at weight reduction on inflammatory biomarkers in
      overweight patients with mild OSA. METHODS AND RESULTS: Patients were randomized
      to supervised intensive lifestyle intervention group (N=28) or to control group
      (N=31), which received routine lifestyle advices. Circulating concentrations of
      pro- and anti-inflammatory mediators were measured before and after the 1-year
      intervention. The concentrations of two pro-inflammatory mediators, high
      sensitivity C-reactive protein (hsCRP) and interleukin (IL)-6, decreased
      significantly in both groups. Although the changes in inflammatory biomarkers
      favored the supervised lifestyle intervention, the only significant reduction
      observed between the groups was for the anti-inflammatory IL-1 receptor
      antagonist (IL-1RA). The change in hsCRP was associated with apnea-hypopnea
      index, and improving night-time oxygen saturation was related to tumor necrosis
      factor alpha. IL-1RA and IL-6 were associated with insulin metabolism.
      CONCLUSION: Weight loss resulted in reductions in concentrations of some pro- and
      anti-inflammatory mediators in overweight patients with mild OSA, overall
      favoring the supervised lifestyle intervention. These findings suggest that more
      intensive treatment of obesity in OSA patients might be well-justified.

PMID- 21193296
TI  - Influence of serum leptin levels on future overweight risk in Korean children.
AB  - BACKGROUND AND AIMS: Leptin is an important regulator of energy metabolism. It is
      considered to be positively related to body adiposity and metabolic disorders in
      obese adults and children. The purpose of this study was to evaluate the
      relationship between baseline circulating leptin, insulin and adiponectin levels
      and future overweight and metabolic risks in a paediatric population-based
      cohort. METHODS AND RESULTS: First-grade students, who entered elementary school
      at age 7 years in Gwacheon, a Korean city, were enrolled in this cohort study,
      and followed from 1st grade to 5th grade. Annual physical examinations from 2005
      to 2009 were performed. In 2006, the levels of serum glucose, insulin, leptin and
      adiponectin and lipid profiles were examined. In 2008, the above parameters,
      except for adiponectin, were measured again in 381 children (202 boys and 179
      girls) who participated. In 2006, 10.2% of the children were overweight (body
      mass index (BMI) >= 85th percentile), and after 2 years, an additional 3% became
      overweight. Compared with insulin and adiponectin, leptin was most highly
      associated with current and future BMI, and percent body fat. Boys in the highest
      tertile for initial leptin (T3) showed the highest prevalence of overweight and
      metabolic risk scores among three leptin tertile groups. Girls showed the same
      trends as boys. High initial leptin levels could be predictive of greater future
      BMI and metabolic risk score (p < 0.001). CONCLUSION: These results suggest that
      elevated serum leptin concentrations among the childhood population could be a
      marker for future BMI and metabolic disorders.

PMID- 21193292
TI  - Prognostic significance of serum uric acid in outpatients with chronic heart
      failure is complex and related to body mass index: data from the IN-CHF Registry.
AB  - BACKGROUND AND AIMS: In the field of cardiovascular diseases, elevated levels of
      serum uric acid (UA) reflect a marked activation of the xanthine oxidase pathway
      with increase in free radicals production; it is often associated with an
      inflammatory state, oxygen consumption and endothelial dysfunction. All these
      associations have been also confirmed in heart failure (HF) but the
      pathophysiological role of UA in this setting is not well understood. The aim of
      this study was to evaluate the prognostic role of UA in outpatients enrolled in
      the Italian Registry of Congestive Heart Failure (IN-CHF). METHODS AND RESULTS:
      All patients met the European Society of Cardiology (ESC) criteria for diagnosis
      of HF. We considered patients with complete clinical data and UA level available
      at the baseline and at 1-year follow-up. The study population was composed of 877
      patients aged 63 +/- 12 years. One-year mortality was 10.8% and dead patients had
      a higher level of UA than survivors (7.1 mg dl-1 vs 6.6 mg dl-1, p < 0.0207). In
      multivariable full model of analysis, UA did not result in an independent
      predictor of death in overall population, but only in patients with low body mass
      index (BMI) (<=22 kg m-2) (hazard ratio (HR): 2.38, 95% confidence interval (CI)
      1.36-4.18). In this subgroup, a statistically significant gradual relationship
      between UA and survival was detected starting from values higher than 8 mg dl-1.
      CONCLUSION: Elevated level of UA is not an independent predictor of mortality in
      chronic HF, but it markedly worsens outcome if associated with low level of BMI.
      This association is likely an indicator of chronic inflammatory and catabolic
      state.

PMID- 21193294
TI  - Gender differences in copper, zinc and selenium status in diabetic-free metabolic
      syndrome European population - the IMMIDIET study.
AB  - BACKGROUND AND AIMS: The European 'IMMIDIET' study was designed to evaluate the
      effect of genetic and dietary habit interactions on cardiovascular disease risk
      factors in non-diabetic subjects. Copper, zinc and selenium are involved in redox
      balance and modifications of their homeostasis could be associated with metabolic
      syndrome. Because few studies have dealt with trace element status in metabolic
      syndrome with conflicting results, we aimed at investigating the relationships
      between plasma copper, zinc and selenium concentrations and metabolic syndrome in
      the IMMIDIET population. METHODS AND RESULTS: Male-female couples born and living
      in Abruzzo, Italy (n = 271); Limburg, Belgium (n = 267), southwest part of
      London, England (n = 263) and 205 Italian-Belgian mixed couples living in Belgium
      were enrolled. Data on medical history, hypertension and blood lipid profile,
      medication use, smoking and alcohol habits, physical activity and socioeconomic
      status were collected using a standardised questionnaire. Anthropometric, blood
      pressure, glucose, insulin, lipid profile and copper, zinc and selenium
      measurements were performed. Participants were classified in two groups according
      to the presence of metabolic syndrome (Yes/No). Comparison between these two
      groups, performed separately in men and women, indicated no association in men
      whereas, in women, metabolic syndrome was associated with higher plasma selenium
      concentrations (odds ratio (OR) = 1.55(1.28-1.89)); this association remained
      significant after adjustment for age, group, social status, physical activity,
      energy intake, alcohol consumption, smoking and hormonal status (OR = 1.33 (1.06
      1.67)). CONCLUSION: Our results indicate gender differences in the association
      between plasma selenium concentration and metabolic syndrome without diabetes and
      may suggest a sub-clinical deleterious effect of high selenium status in women.

PMID- 21193297
TI  - Cultural and historical aspects of Mediterranean nuts with emphasis on their
      attributed healthy and nutritional properties.
AB  - BACKGROUND AND AIMS: Nuts have been part of the human diet since prehistoric
      times. The aim of the present article is to describe the most important
      historical and cultural aspects of nut consumption throughout history. DATA
      SYNTHESIS: We discuss the following historical aspects of nuts originating in the
      Mediterranean: prehistory, the Egyptian civilization, their spread through the
      Mediterranean region by the Greek, Phoenician and Roman civilizations, and their
      reintroduction into Europe by means of the Al-Andalus culture. Particular
      emphasis is placed on the healthy and nutritional attributes that nuts have had
      throughout history. We also consider the role of the first globalization of food-
      the exchange of nuts between continents--and discuss the symbolism that nuts have
      had for humans throughout history in the context of cultural aspects of the
      Mediterranean region. CONCLUSIONS: Nuts and fruits are probably the earliest
      foods consumed by humans and are considered to be important because of their
      nutritional properties. Nuts have also been used in the past by different
      civilizations as drugs to prevent or treat several diseases.

PMID- 21193299
TI  - Editorial on the occasion of the 25th anniversary of the Journal of Trace
      Elements in Medicine and Biology.

PMID- 21193298
TI  - INS VNTR class genotype and the function of isolated human islets.

PMID- 21193301
TI  - Nutritional modulation of the gut microbiota and immune system in preterm
      neonates susceptible to necrotizing enterocolitis.
AB  - The gastrointestinal inflammatory disorder, necrotizing enterocolitis (NEC), is
      among the most serious diseases for preterm neonates. Nutritional,
      microbiological and immunological dysfunctions all play a role in disease
      progression but the relationship among these determinants is not understood. The
      preterm gut is very sensitive to enteral feeding which may either promote gut
      adaptation and health, or induce gut dysfunction, bacterial overgrowth and
      inflammation. Uncontrolled inflammatory reactions may be initiated by
      maldigestion and impaired mucosal protection, leading to bacterial overgrowth and
      excessive nutrient fermentation. Tumor necrosis factor alpha, toll-like receptors
      and heat-shock proteins are identified among the immunological components of the
      early mucosal dysfunction. It remains difficult, however, to distinguish the
      early initiators of NEC from the later consequences of the disease pathology. To
      elucidate the mechanisms and identify clinical interventions, animal models
      showing spontaneous NEC development after preterm birth coupled with different
      forms of feeding may help. In this review, we summarize the literature and some
      recent results from studies on preterm pigs on the nutritional, microbial and
      immunological interactions during the early feeding-induced mucosal dysfunction
      and later NEC development. We show that introduction of suboptimal enteral
      formula diets, coupled with parenteral nutrition, predispose to disease, while
      advancing amounts of mother's milk from birth (particularly colostrum) protects
      against disease. Hence, the transition from parenteral to enteral nutrition
      shortly after birth plays a pivotal role to secure gut growth, digestive
      maturation and an appropriate response to bacterial colonization in the sensitive
      gut of preterm neonates.

PMID- 21193302
TI  - Susceptibility to intestinal tumorigenesis in folate-deficient mice may be
      influenced by variation in one-carbon metabolism and DNA repair.
AB  - Low dietary folate is associated with increased risk of colorectal cancer. In
      earlier work, we showed that folate deficiency induced intestinal tumors in
      BALB/c but not C57Bl/6 mice through increased dUTP incorporation into DNA with
      consequent DNA damage. To determine whether strain differences between one-carbon
      metabolism and DNA repair pathways could contribute to increased tumorigenesis in
      BALB/c mice, we measured amino acids and folate in the normal intestinal tissue
      of both strains fed a control diet or a folate-deficient diet. We also determined
      the expression of critical folate-metabolizing enzymes and several DNA repair
      enzymes. BALB/c mice had lower intestinal serine (major cellular one-carbon
      donor), methionine and total folate than C57Bl/6 mice under both dietary
      conditions. BALB/c mice had higher messenger RNA and protein levels of three
      folate-interconverting enzymes: trifunctional methyleneTHF (5,10
      methylenetetrahydrofolate) dehydrogenase-methenylTHF cyclohydrolase-formylTHF (10
      formyltetrahydrofolate) synthetase 1, bifunctional methyleneTHF dehydrogenase
      methenylTHF cyclohydrolase and methylenetetrahydrofolate reductase. This pattern
      of expression could limit the availability of methyleneTHF for conversion of dUMP
      to dTMP. BALB/c mice also had higher levels of uracil DNA glycosylase 2 protein
      without an increase in the rate-limiting DNA polymerase beta enzyme, compared
      with C57Bl/6 mice. We conclude that BALB/c mice may be more prone to DNA damage
      through decreased amounts of one-carbon donors and the diversion of methyleneTHF
      away from the conversion of dUMP to dTMP. In addition, incomplete excision repair
      of uracil in DNA could lead to accumulation of toxic repair intermediates and
      promotion of tumorigenesis in this tumor-susceptible strain.

PMID- 21193303
TI  - An array of field-effect nanoplate SOI capacitors for (bio-)chemical sensing.
AB  - An array of individually addressable nanoplate field-effect capacitive (bio
      )chemical sensors based on an SOI (silicon-on-insulator) structure has been
      developed. The isolation of the individual capacitors was achieved by forming a
      trench in the top Si layer with a thickness of 350 nm. The realized sensor array
      allows addressable biasing and electrical readout of multiple nanoplate EISOI
      (electrolyte-insulator-silicon-on-insulator) capacitive biosensors on the same
      SOI chip as well as differential-mode measurements. The feasibility of the
      proposed approach has been demonstrated by realizing sensors for the pH and
      penicillin concentration detection as well as for the label-free electrical
      monitoring of polyelectrolyte multilayers formation and DNA (deoxyribonucleic
      acid)-hybridization event. A potential change of ~ 120 mV has been registered
      after the DNA hybridization for the sensor immobilized with perfectly matched
      single-strand DNA, while practically no signal changes have been observed for a
      sensor with fully mismatched DNA. The realized examples demonstrate the potential
      of the nanoplate SOI capacitors as a new basic structural element for the
      development of different types of field-effect biosensors.

PMID- 21193304
TI  - WITHDRAWN: Oral disease and risk of esophageal and gastric cancer in a nationwide
      nested case-control study in Sweden.
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- 21193305
TI  - Effect of oxygen dosing point and mixing on the microaerobic removal of hydrogen
      sulphide in sludge digesters.
AB  - Limited oxygen supply to anaerobic sludge digesters to remove hydrogen sulphide
      from biogas was studied. Micro-oxygenation showed competitive performance to
      reduce considerably the additional equipment necessary to perform biogas
      desulphurization. Two pilot-plant digesters with an HRT of ~ 20 d were micro
      oxygenated at a rate of 0.25 NL per L of feed sludge with a removal efficiency
      higher than 98%. The way of mixing (sludge or biogas recirculation) and the point
      of oxygen supply (headspace or liquid phase) played an important role on hydrogen
      sulphide oxidation. While micro-oxygenation with sludge recirculation removed
      only hydrogen sulphide from the biogas, dissolved sulphide was removed if micro
      oxygenation was performed with biogas recirculation. Dosage in the headspace
      resulted in a more stable operation. The result of the hydrogen sulphide
      oxidation was mostly elemental sulphur, partially accumulated in the headspace of
      the digester, where different sulphide-oxidising bacteria were found.

PMID- 21193306
TI  - Model-based design of different fedbatch strategies for phenol degradation in
      acclimatized activated sludge cultures.
AB  - Microbial degradation of phenol was studied using batch and fedbatch cultures of
      acclimatized activated sludge under a wide range of phenol (0-793 mg l(-1)) and
      biomass (0.74-6.7 g l(-1)) initial concentrations. As cell growth continued after
      total phenol removal, the production and later consumption of a main metabolic
      intermediate was considered the step governing the biodegradation kinetics. A
      model that takes explicitly into account the kinetics of the intermediate was
      developed by introducing a specific growth rate model associated with its
      consumption and the incorporation of a dual-substrate inhibitory effect on phenol
      degradation. Biomass growth and phenol removal were adequately predicted in all
      the cultures. Moreover, the model-based design of the fedbatch feeding strategies
      allowed driving separately the phenol degradation under substrate-limitation and
      substrate-inhibition modes. A sensitivity analysis was also performed in order to
      establish the importance of the parameters in the accuracy of model predictions.

PMID- 21193307
TI  - Environmentally friendly preparation of pectins from agricultural byproducts and
      their structural/rheological characterization.
AB  - Apple pomace which is the main waste of fruit juice industry was utilized to
      extract pectins in an environmentally friendly way, which was then compared with
      chemically-extracted pectins. The water-based extraction with combined physical
      and enzymatic treatments produced pectins with 693.2 mg g(-1) galacturonic acid
      and 4.6% yield, which were less than those of chemically-extracted pectins.
      Chemically-extracted pectins exhibited lower degree of esterification (58%) than
      the pectin samples obtained by physical/enzymatic treatments (69%), which were
      also confirmed by FT-IR analysis. When subjected to steady-shear rheological
      conditions, both pectin solutions were shown to have shear-thinning properties.
      However, decreased viscosity was observed in the pectins extracted by combined
      physical/enzymatic methods which could be mainly attributed to the presence of
      more methyl esters, thus limiting polymer chain interactions. Moreover, the
      pectins which were extracted by combined physical/enzymatic treatments, showed
      less elastic properties under high shear rate conditions, compared to the
      chemically-extracted pectins.

PMID- 21193308
TI  - Exploration of SAR regarding glucose moiety in novel C-aryl glucoside inhibitors
      of SGLT2.
AB  - In order to investigate SAR regarding glucose moiety in novel C-aryl glucoside
      SGLT2 inhibitors containing a thiazole motif, a series of chemical modifications
      on glucose was conducted to explore potential utility as a suitable replacement
      of glucose per se. Among the compounds prepared, deshydroxy 29 (IC(50)=7.01nM)
      demonstrated the best in vitro inhibitory activity against SGLT2 in this series
      to date. But, none of the compounds were better than the parent molecule 5
      (IC(50)=1.75nM).

PMID- 21193309
TI  - Synthesis, hypolipidemic and hypoglycemic activity of some novel 2-(4-(2
      substituted aminothiazole-4-yl) phenoxy)-2-methyl propanoic acid derivatives.
AB  - An improved synthetic protocol for a novel series of 2-(4-(2-substituted
      aminothiazole-4-yl) phenoxy)-2-methyl propanoic acid derivatives has been
      developed using different methods of synthesis. The synthesized compounds are
      evaluated for their hypolipidemic and hypoglycemic activity by high fat diet
      induced hyperlipidemia and hyperglycemia in Sprague-Dawley rats.

PMID- 21193310
TI  - Tetrahydroquinoline derivatives as opioid receptor antagonists.
AB  - Opioid receptors play an important role in both behavioral and homeostatic
      functions. We herein report tetrahydroquinoline derivatives as opioid receptor
      antagonists. SAR studies led to the identification of the potent antagonist 2v,
      endowed with 1.58nM (K(i)) functional activity against the MU opioid receptor.
      DMPK data suggest that novel tetrahydroquinoline analogs may be advantageous in
      peripheral applications.

PMID- 21193311
TI  - Shp2 protein tyrosine phosphatase inhibitor activity of estramustine phosphate
      and its triterpenoid analogs.
AB  - Shp2 protein tyrosine phosphate (PTP) is a novel target for anticancer drug
      discovery. We identified estramustine phosphate as a Shp2 PTP inhibitor from the
      National Cancer Institute Approved Oncology Drug set. A focused structure
      activity relationship study indicated that the 17-phosphate group is required for
      the Shp2 PTP inhibitor activity of estramustine phosphate. A search for
      estramustine phosphate analogs led to identification of two triterpenoids,
      enoxolone, and celastrol, having Shp2 PTP inhibitor activity. With the previously
      reported PTP1B inhibitor trodusquemine, our study reveals steroids and
      triterpenoids with negatively charged phosphate, carboxylate, or sulfonate groups
      as novel pharmacophores of selective PTP inhibitors.

PMID- 21193312
TI  - Synthesis and bio-evaluation of aryl hydrazono esters for oviposition responses
      in Aedes albopictus.
AB  - A novel series of aryl hydrazono esters (AHE) (1-13) were synthesized (yield 76
      98%) to study the oviposition responses in Aedes albopictus (Skuse) mosquitoes
      for the first time. At a concentration of 10MUgml(-1) in dual choice experiment,
      among the screened compounds, AHE-12 showed remarkable oviposition attractant
      activity with an oviposition activity index (OAI) of +0.299 (greater than 95%
      confidence limit) comparable to p-cresol (OAI +0.320) which is well-reported
      oviposition attractant for Aedes aegypti. Conversely, AHE-10 exhibited highest
      oviposition deterrent activity with OAI -0.247. The possible utilization of these
      compounds will be in integrated vector management strategies.

PMID- 21193313
TI  - Dual-task effects of spontaneous speech and executive function on gait in aging:
      exaggerated effects in slow walkers.
AB  - This study compared the effects of spontaneous speech and executive function on
      gait and investigated the effects of single-task gait speed on dual-task costs.
      Twenty-one older adults (74.7 years, SD 5.9) and 23 younger adults (22 years, SD
      1.2) walked for 60s while performing an auditory Stroop task and a spontaneous
      speech task; they also performed each task in isolation. Walking while talking
      significantly reduced gait speed in both groups; however, only older adults
      experienced significant cognitive-motor interference during the Stroop task.
      Stride duration variability and gait symmetry were also affected by the speech
      task in older but not younger adults. Dual-task costs on gait speed were greater
      in slow-walking older adults than fast walkers. These results demonstrate that
      spontaneous speech is a highly demanding task that has a profound impact on gait
      in older adults, especially those with gait speed <1 m/s.

PMID- 21193314
TI  - Structural and biochemical study on the inhibitory activity of derivatives of 5
      nitro-furan-2-carboxylic acid for RNase H function of HIV-1 reverse
      transcriptase.
AB  - Rapid emergence of drug-resistant variants is one of the most serious problems in
      chemotherapy for HIV-1 infectious diseases. Inhibitors acting on a target not
      addressed by approved drugs are of great importance to suppress drug-resistant
      viruses. HIV-1 reverse transcriptase has two enzymatic functions, DNA polymerase
      and RNase H activities. The RNase H activity is an attractive target for a new
      class of antiviral drugs. On the basis of the hit chemicals found in our previous
      screening with 20,000 small molecular-weight compounds, we synthesized
      derivatives of 5-nitro-furan-2-carboxylic acid. Inhibition of RNase H enzymatic
      activity was measured in a biochemical assay with real-time monitoring of
      florescence emission from the digested RNA substrate. Several derivatives showed
      higher inhibitory activities that those of the hit chemicals. Modulation of the 5
      nitro-furan-2-carboxylic moiety resulted in a drastic decrease in inhibitory
      potency. In contrast, many derivatives with modulation of other parts retained
      inhibitory activities to varying degrees. These findings suggest the binding mode
      of active derivatives, in which three oxygen atoms aligned in a straight form at
      the nitro-furan moiety are coordinated to two divalent metal ions located at
      RNase H reaction site. Hence, the nitro-furan-carboxylic moiety is one of the
      critical scaffolds for RNase H inhibition. Of note, the RNase H inhibitory
      potency of a derivative was improved by 18-fold compared with that of the
      original hit compound, and no significant cytotoxicity was observed for most of
      the derivatives showing inhibitory activity. Since there is still much room for
      modification of the compounds at the part opposite the nitro-furan moiety,
      further chemical conversion will lead to improvement of compound potency and
      specificity.

PMID- 21193315
TI  - 2-Substituted (S)-2-(3,3-dimethyl-1-oxo-10,10a-dihydroimidazo[1,5-b]isoquinolin
      2(1H,3H,5H)-yl)acetic acids: Conformational prediction, synthesis, anti
      thrombotic and vasodilative evaluation.
AB  - (S)-1,2,3,4-Tetrahydroisoquinoline-3-carboxylic acid (TIC) can inhibit thrombosis
      by inhibiting platelet aggregation. The investigation of amino acids modified TIC
      reveals that a stretching conformation is critical for high anti-thrombotic
      activity. The conformational modeling shows that introducing a ring into amino
      acid modified TIC results in a desirable stretching conformation. According to
      this hypothesis, we synthesized seventeen novel 2-substituted (S)-2-(3,3-dimethyl
      1-oxo-10,10a-dihydroimidazo[1,5-b]isoquinolin-2(1H,3H,5H)-yl)acetic acids (5a-q).
      In the in vitro anti-platelet aggregation assay, for ADP-induced platelet
      aggregation the IC(50) values of 5a-q are 1.8-3.4-folds lower than that of TIC.
      In the in vivo anti-thrombotic assay, the effective dose of 5a-q was 167-folds
      lower than that of TIC. The vessel strip assay showed that 5a-q had mild
      vasorelaxation activity.

PMID- 21193316
TI  - Neutrons in the low-background Ge-detector vicinity estimated from different
      activation reactions.
AB  - Neutrons produced by cosmic-ray muons in a detector shield and other surrounding
      materials can be captured or scattered by different nuclei in subsequent
      reactions. The gamma photons emitted after nuclear capture or scattering from
      produced Ge isotopes are used to estimate the neutron flux. If a bulk sample
      measured in some low background gamma spectroscopy system contains hydrogen, a
      high energy photon (of energy 2223keV) emitted in the process of deuterium
      production can be used to estimate the flux of thermal neutrons. Results obtained
      from the interaction of neutrons with H as well as with some Ge isotopes are
      computed and compared in this paper. The passive lead shield in a detector system
      is a source of a significant fraction of the gamma radiation induced by capture
      and inelastic scattering of neutrons. We also used gamma lines emitted by several
      Pb isotopes to estimate the neutron flux near a detector.

PMID- 21193317
TI  - Calibration of an in-situ BEGe detector using semi-empirical and Monte Carlo
      techniques.
AB  - In the case of a nuclear or radiological accident a rapid estimation of the
      qualitative and quantitative characteristics of the potential radioactive
      pollution is needed. For aerial releases the radioactive pollutants are finally
      deposited on the ground forming a surface source. In this case, in-situ gamma-ray
      spectrometry is a powerful tool for the determination of ground pollution. In
      this work, the procedure followed at the Nuclear Engineering Department of the
      National Technical University of Athens (NED-NTUA) for the calibration of an in
      situ Broad Energy Germanium (BEGe) detector, for the determination of gamma
      emitting radionuclides deposited on the ground surface, is presented. BEGe
      detectors due to their technical characteristics are suitable for the analysis of
      photons in a wide energy region. Two different techniques were applied for the
      full-energy peak efficiency calibration of the BEGe detector in the energy region
      60-1600 keV: Full-energy peak efficiencies determined using the two methods agree
      within statistical uncertainties.

PMID- 21193318
TI  - Oleosin di-or tri-meric fusions with GFP undergo correct targeting and provide
      advantages for recombinant protein production.
AB  - Plant oleosins are small proteins embedded within the phospholipid monolayer
      separating the triacylglycerol storage site of embryo-located oilbodies from the
      cytoplasm of oilseed cells. The potential of oleosins to act as carriers for
      recombinant proteins foreign to plant cells has been well established. Using this
      approach, the recombinant polypeptide is accumulated in oilbodies as a fusion
      with oleosin. DNA constructs having tandemly arranged oleosins followed by GFP or
      flanked by oleosins were used to transform Arabidopsis plants. In all cases the
      green fluorescence revealed that the fusion polypeptide had a native conformation
      and the recombinant proteins were correctly targeted to seed oilbodies.
      Mobilization of lipids was not retarded when using homo-dimer or -trimer oleosin
      fusions, since seed production, germination rates and seedling establishment were
      similar among all constructs, and comparable to wild-type Arabidopsis plants.
      Plant physiology and growth of recombinant lines were similar to wild-type
      plants. The construct specifying two oleosins flanking the GFP polypeptide
      revealed interesting properties regarding both the accumulation and the relative
      stability of the oilbody protein assembly. Although expression levels varied
      among transgenic lines, those transgenes accumulated significantly higher levels
      of fusion proteins as compared to previously reported values obtained by a single
      oleosin configuration, reaching up to 2.3% of the total embryo proteins. These
      results shows that the expression cassettes comprising three oleosin molecules in
      frame to the GFP molecule or two oleosins flanking the GFP could be advantageous
      over the single-oleosin configuration for higher production and better
      commercialization of this plant biotechnological platform without jeopardizing
      plant vigour and physiology or oilbody stability.

PMID- 21193319
TI  - Spontaneous expectoration of an obstructive fibrinous tracheal pseudomembrane
      after tracheal intubation.
AB  - We report a rare and potentially life-threatening complication related to
      tracheal intubation in the formation of obstructive tracheal pseudomembrane. In
      the present case, the pseudomembrane was spontaneously expectorated; this is very
      unusual and not been reported before. This condition was first misdiagnosed as
      edema subglottis. Then, computed tomography revealed a stenosis of the middle
      trachea, but subsequent flexible bronchoscopy was unable to provide additional
      information regarding its nature. Before attending a rigid bronchoscopy, planned
      to better define the cause of stenosis, a thick annular membrane was scraped away
      with a large amount of coughing. After that, the patient's respiratory symptoms
      completely resolved. Control at 1 and again 3 months later showed no further
      tracheal stenosis. The diagnosis of obstructive tracheal pseudomembrane should be
      considered in cases of post-extubation stridor. Flexible bronchoscopic guidance
      after extubation may allow to diagnose such a complication earlier, but rigid
      bronchoscopy remains the treatment of choice.

PMID- 21193320
TI  - Hemodynamic performance of the Medtronic Mosaic and Perimount Magna aortic
      bioprostheses: five-year results of a prospectively randomized study.
AB  - OBJECTIVE: Clinical outcomes of patients undergoing aortic valve replacement may
      be influenced by the presence of residual gradients and patient-prosthesis
      mismatch. The aim of this study was to compare hemodynamic performance and
      clinical outcomes at 5 years after prospectively randomized porcine versus bovine
      aortic valve replacement. We also aimed to determine the effects of valve
      hemodynamics on left ventricular (LV) mass regression. METHODS: A total of 108
      patients undergoing aortic valve replacement were randomized to receive either
      the Medtronic Mosaic (MM) porcine (n=54) or the Edwards Perimount Magna (EPM)
      bovine pericardial prosthesis (n=54). Clinical outcomes, mean gradients,
      effective orifice area and LV mass regression were evaluated at 1 and 5 years
      after surgery. Follow-up echocardiograms were performed on 106 (98%) and 87 (92%)
      patients, respectively. RESULTS: Preoperative characteristics were similar
      between groups. Mean aortic annulus diameter and mean implant size were
      comparable in both groups. At 1 and 5 years, mean transprosthetic gradients were
      lower in the EPM group: EPM 10.3+/-3.4mmHg versus MM 16.3 +/- 7.6 mmHg (p<0.0001)
      and EPM 9.6 +/- 3.5 mmHg versus MM 16.8 +/- 8.7 mmHg (p<0.0001), respectively.
      Similarly, indexed effective orifice areas (IEOA) at 1 and 5 years were
      significantly greater in the EPM group: EPM 1.10 +/- 0.22 cm(2)m(-2) versus MM
      0.96 +/- 0.22 cm(2)m(-2) (p<0.004) and EPM 1.02 +/- 0.25 cm(2)m(-2) versus MM
      0.76 +/- 0.19 cm(2)m(-2) (p<0.0001), respectively. At 5 years, the incidence of
      patient-prosthesis mismatch (IEOA <=0.85 cm(2)m(-2)) was significantly lower in
      the EPM group: EPM 22.9% vs MM 73.9% (p<0.0001). Such differences were similar
      when analysis was stratified by surgically measured annular size and implant
      valve size. During the first year after surgery, both groups demonstrated similar
      regression of LV mass index (MM -26.3 +/- 43 gm(2) vs EPM -30.1 +/- 36 gm(-2);
      p=0.8); however, at 5 years, regression of LV mass index was significantly
      greater in the EPM group: (EPM -47.4 +/- 35 gm(-2) vs -4.4 +/- 36 gm(-2);
      p<0.0001). Five-year survival was 79.6 +/- 4.1% in the MM group and 94.4 +/- 2.2%
      in the EPM group (p=0.03). CONCLUSIONS: At 5 years, the EPM valve was
      significantly superior to the MM prosthesis with regard to hemodynamic
      performance, incidence of patient-prosthesis mismatch and regression of LV mass
      index. The hemodynamic superiority of the EPM prostheses in comparison to MM
      prostheses demonstrated at 1 year, increased significantly over time.

PMID- 21193321
TI  - Surgical treatment of stage III thymic tumors: a multi-institutional review from
      four Italian centers.
AB  - OBJECTIVE: Radical surgery is the cornerstone of treatment for thymic tumors, but
      a complete surgical resection in stage III is not always achievable; and
      recurrence of disease is not rare. We reviewed the results of four centers with
      large experience in multimodality treatment of stage III thymic tumors. METHODS:
      Between 1980 and 2009, 249 patients (137 males: 112 females; median age 50 years)
      with stage III thymic tumors underwent surgery. Myasthenia gravis (MG) was
      present in 110 (44.2%) patients. A total of 94 (37.7%) patients received
      induction chemotherapy and 205 (82.7%) had adjuvant treatments. RESULTS: Thirty
      day mortality was 0.8%. A total of 203 (81.6%) had R0, 26 (10.4%) R1 and 20 (8%)
      R2 resection. World Health Organization (WHO) histotype was: A in 2.4%, AB in
      15.3%, B1 in 16.5%, B2 in 31.3%, B3 in 22.1%, and thymic carcinoma in 12.4%. The
      R0 rate was lower in patients who received induction chemotherapy (p=0.04), in B1
      B2-thymic carcinoma histotypes (p = 0.05), and in patients without MG (p = 0.04).
      Overall 10-year survival rate was 64%; tumor-related and disease-free survival
      were 76% and 74%, respectively. At univariate analysis, R2 resection (p <
      0.0001), recurrence of disease (p < 0.0001), absence of MG (p = 0.0009), thymic
      carcinoma (p = 0.002), age more than 50 years (p = 0.01), and vascular invasion
      (p < 0.0001) were predictors of poor survival. At multivariate analysis, type of
      resection (p < 0.0001), vascular involvement (p = 0.007), and recurrent disease
      (p < 0.0001) were independent predictors of prognosis. During follow-up, 43
      (21.2%) patients developed recurrence. Patients with recurrence, who underwent
      redo surgery (n = 24), showed a similar survival to patients without recurrence.
      CONCLUSIONS: Multimodality treatment of stage III thymic tumors achieved good
      survival. Radical surgery, even at recurrence, seems to be the most important
      prognostic factor.

PMID- 21193322
TI  - Circulating levels and dietary intake of the advanced glycation end-product
      marker carboxymethyl lysine in chronic kidney disease patients on conservative
      predialysis therapy: a pilot study.
AB  - OBJECTIVE: Advanced glycation end-products (AGEs) are proposed to influence
      inflammatory pathways and cardiovascular risk in chronic kidney disease (CKD).
      Dietary AGEs are believed to sustain circulating levels and toxicity in this
      condition. DESIGN AND PATIENTS: We investigated this aspect in a cross-sectional
      pilot study measuring levels of the AGE marker carboxymethyl lysine (CML) and
      fluorescent AGEs in the blood of pre-dialysis patients with CKD and hemodialysis
      (HD) patients (n = 10 each), and in a group of matched healthy controls (Ctr).
      METHODS: Plasma CML was measured by immuno-dot blot and fluorescent AGEs were
      determined by high-performance liquid chromatography (HPLC) analysis measuring
      the fluorescence of the cross-link pentosidine. The dietary intake of CML was
      assessed by dietary recall to trace total AGE intake in patients with CKD and the
      Ctr group. All the subjects included in the study were assessed for dietary
      intake while maintaining their usual diet. Main exclusion criteria for patients
      with CKD and HD were severe protein-caloric malnutrition and inflammation
      (measured by high sensitivity C-reactive protein and interleukin-6 levels).
      RESULTS: Plasma CML, as well as free and protein-bound fluorescent AGEs,
      significantly increased in CKD and even more in HD patients than that of the Ctr
      group. In patients with CKD, the average dietary intake of CML was less than half
      than that of the Ctr group (6 vs. 13 MU/day) and the lowered protein intake
      adopted spontaneously by these patients appear to explain this finding.
      CONCLUSIONS: The results show that the intake of CML does not affect circulating
      levels of this as well as of other AGEs, in well nourished predialysis CKD
      patients.

PMID- 21193323
TI  - Predictive value of malnutrition markers for mortality in peritoneal dialysis
      patients.
AB  - INTRODUCTION: Alterations in nutritional status have been described as important
      predictors of mortality in patients with chronic kidney disease (CKD). However,
      the association between multiple markers for nutritional status and the mortality
      rates of patients with CKD on peritoneal dialysis (PD) has not yet been
      illustrated in previously published data, particularly by using the new
      definition of protein energy wasting (PEW). OBJECTIVE: To evaluate the predictive
      value of malnutrition markers for mortality rates, on the basis of the PEW
      definition, of PD patients. MATERIALS AND METHODS: At the start of PD treatment,
      the nutritional status of 199 patients (mean age, 56 +/- 13.3 years; 53% females)
      was evaluated. Body mass index (BMI), arm circumference, mid-arm muscle
      circumference, protein and caloric intake (by using a 3-day food record), and
      serum albumin were all recorded, as well as a subjective global assessment (SGA)
      and presence of PEW. Cut-off points were defined on the basis of the consensus of
      the International Society for Renal Nutrition and Metabolism (albumin, <3.8 g/dL;
      BMI, <23 kg/m(2); mid-arm muscle circumference, >10% in comparison with the 50th
      percentile for the reference population; protein intake, <0.8 g/kg/daily; caloric
      intake, <25 kcal/kg/daily). The data were obtained retrospectively between the
      years 2001 and 2008 on the basis of routine nutritional evaluation. Patients were
      monitored for fatal events from all possible causes. RESULT: The mean BMI for the
      population was 26.6 +/- 5.0 kg/m(2). A median protein intake of 0.94 (0.18 to
      4.57) g/kg/daily was reported and 60.3% of the patients reported a protein intake
      of <0.8 g/kg/daily. With respect to caloric intake, 38.7% of the patients
      consumed <25 kcal/kg/daily. A median of 3.5 (1.4 to 5.3) g/dL for serum albumin
      was observed and 29.3% of the patients presented values of <3.8 g/dL. PEW was
      diagnosed in 17.5% of patients. In the univariate model, being of age >65 years
      (P = .002), cardiovascular disease (P < .001), diabetes mellitus (P = .02), SGA
      (P = .02), and albumin (P = .002), were all significant markers for mortality.
      The presence of patients aged >65 years (P = .02), with diabetes mellitus (P =
      .057), cardiovascular disease (P = .005), and albumin were considered as
      independent factors for mortality in this study. CONCLUSION: SGA, albumin, and
      PEW were the only nutritional markers found to be associated with mortality in
      this cohort of PD patients. In the multivariate analysis, after adjusting for
      classic mortality risk factors, only patients with hypoalbuminemia were found to
      be at a high risk for mortality at follow-up. These results may be limited by the
      number of observations and a necessity for confirmation in larger prospective
      studies.

PMID- 21193325
TI  - Lung transplantation in older adults: how old is too old?

PMID- 21193324
TI  - Appetite-regulating hormones in chronic kidney disease patients.
AB  - OBJECTIVE: Inflammation and loss of appetite is the most common problem in
      patients with chronic kidney disease (CKD). This comparative cross-sectional
      study aimed to characterize the changes in circulating levels of ghrelin,
      obestatin, leptin, all of which have an effect on food intake, and
      proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-alpha (TNF
      alpha) in patients with CKD who were undergoing different treatments. DESIGN AND
      SETTING: Study participants included 36 patients who had undergone hemodialysis
      (body mass index [BMI]: 22.3 +/- 4.17 kg/m(2)); 41 who had undergone peritoneal
      dialysis (BMI: 23.5 +/- 3.10 kg/m(2)), 30 with early stage CKD (BMI: 24.4 +/-
      3.32 kg/m(2)), and 31 healthy subjects (24.3 +/- 2.14 kg/m(2)). The patients with
      CKD were kept under a standard diet with restricted salt, potassium, and protein
      intake. INTERVENTION: Levels of leptin, acylated ghrelin, obestatin, TNF-alpha,
      and IL-6 were measured by commercially available enzyme-linked immunosorbent
      assay kits. Total nitrite/nitrate was analyzed using colorimetric assay kit.
      RESULTS: Significantly high leptin levels, accompanied by low acylated ghrelin
      levels, were observed in patients with CKD. Maintenance dialysis did not affect
      these levels. TNF-alpha and IL-6 levels were significantly higher in CKD patients
      than in healthy subjects, the highest being in dialysis patients. Obestatin
      levels were relatively low in patients who had undergone hemodialysis.
      CONCLUSION: Low acyl-ghrelin levels, accompanied with high levels of TNF-alpha
      and IL-6 may be involved in the loss of appetite and poor nutritional status in
      CKD patients.

PMID- 21193326
TI  - Endothelitis in cardiac allograft biopsy specimens: possible relationship to
      antibody-mediated rejection.
AB  - BACKGROUND: The incidence of endothelitis in cardiac transplants, and the
      relationship to clinical symptoms and humoral rejection, is unclear. Recently,
      the finding of intravascular macrophages has been found to represent antibody
      mediated rejection. This study investigated the role of intravascular T
      lymphocytes in antibody-mediated rejection. METHODS: A total of 819 sequential
      biopsy specimens from 93 cardiac allograft recipients were prospectively studied.
      Rejection was graded according to International Society for Heart and Lung
      Transplantation (ISHLT) criteria and inflammatory infiltrates characterized by
      immunohistochemical staining for CD3, CD4, CD8, CD68, and CD20. Endothelitis was
      defined as lymphocyte and macrophage infiltrates within arteriolar, capillary, or
      venular walls, with endothelial swelling, in contrast to perivascular
      inflammation of cellular rejection. Complement C4d was identified in capillary
      walls by immunofluorescent staining and immunohistochemical staining on paraffin
      sections. RESULTS: Endothelitis was identified in 27 specimens (3%) from 14
      patients (15%). ISHLT rejection grades were 0 in 6 specimens, 1R in 20 (1A in 8;
      1B in 12), and 2R (3A) in 1. In all cases, there were admixtures of macrophages
      and T lymphocytes. Inflammation was most prominent in venules. C4d was localized
      in 12 of the 27 specimens (44%). C4d was localized in 31 of 796 specimens without
      endothelitis (p < 0.001). The endothelial infiltrates were CD3, CD4, CD8, and
      CD68+. Twelve of 14 patients had > 0 panel reactive antibodies (PRA), 9 were
      above 10%, and 8 were above 25%; 5 patients were treated for clinical antibody
      mediated rejection, and 4 had possible cardiac allograft vasculopathy by
      ultrasound imaging (mean follow-up, 40 months). CONCLUSION: Endothelitis is
      present in more than 10% of heart transplant recipients and is associated with
      complement deposition on biopsy samples. Approximately 33% of patients have
      clinical evidence of humoral rejection. The eventual risk for developing graft
      vascular disease remains undetermined.

PMID- 21193327
TI  - Normal left ventricular mechanical function and synchrony values by speckle
      tracking echocardiography in the transplanted heart with normal ejection
      fraction.
AB  - BACKGROUND: The purpose of this study was to describe the normal values for
      strain (S), systolic strain rate (SRs) and synchrony by speckle-tracking
      echocardiography (STE) in heart transplant (HTx) recipients who had normal left
      ventricular ejection fraction (LVEF) and no clinically significant complications.
      METHODS: We evaluated S and SRs in 40 HTx patients at 1 year after transplant and
      82 healthy controls with STE using velocity vector imaging. RESULTS: Mean (SD)
      global longitudinal S and SRs, respectively, were lower in the transplant group
      compared with controls [-13.43% (2.39%) vs -17.28% (2.30%), p < 0.001; -0.83
      (0.15) s(-1) vs -0.96 (0.13) s(-1), p < 0.001]. These variables were good for
      differentiating between groups: area under the curve was 0.88 for S and 0.73 for
      SRs. The differences remained significant after adjustment for other clinical
      variables. Global circumferential S and SRs were similar between groups. The
      standard deviation of the global longitudinal S time to peak of the 16 segments
      for HTx and control groups, respectively, was 41.67 (13.53) milliseconds vs 32.57
      (12.81) milliseconds (p < 0.001). With 58.2 milliseconds as a cutoff value to
      define left ventricular synchrony, only 3 (8%) of the HTx patients and 4 (5%) of
      the control subjects were above that value (p = 0.6). CONCLUSION: To our
      knowledge, this is the first study describing normal values for S and SRs and
      synchrony by STE in a HTx population with normal LVEF: longitudinal S and SRs
      were reduced; circumferential deformation indexes were normal; and left
      ventricular synchrony was preserved.

PMID- 21193328
TI  - Remembering en bloc double-lung transplantation.

PMID- 21193329
TI  - The Shah's spleen: its impact on history.

PMID- 21193330
TI  - A triangulating operating platform enhances bimanual performance and reduces
      surgical workload in single-incision laparoscopy.
AB  - BACKGROUND: Single-site laparoscopy (SSL) attempts to further reduce the surgical
      impact of minimally invasive surgery. However, crossed instruments and the
      proximity of the endoscope to the operating instruments placed through one single
      site leads to inevitable instrument or trocar collision. We hypothesized that a
      novel, single-port, triangulating surgical platform (SPSP) might enhance
      performance by improving bimanual coordination and decreasing the surgeon's
      mental workload. STUDY DESIGN: Fourteen participants, proficient in basic
      laparoscopic skills, were tested on their ability to perform a validated
      intracorporeal suturing task by either an SSL approach with crossed articulated
      instruments or a novel SPSP, providing true-right and true-left manipulation.
      Standard laparoscopic (SL) access served as control. Sutures were evaluated using
      validated scoring methods and the National Aeronautics and Space Administration
      Task Load Index was used to rate mental workload. RESULTS: All participants
      proficiently performed intracorporeal knots by SL (mean score 99.0; 95% CI 97.0
      to 100.9). Performance decreased significantly (more than 50%, p < 0.001) with
      the SSL approach using 1 rigid and 1 articulating instrument in a cross-wise
      manner (mean score 39.2; 95% CI 28.3 to 50.1). The use of the SPSP significantly
      enhanced bimanual coordination (mean score 67.6; 95% CI 61.3 to 73.9; p < 0.001).
      Participants recorded lower mental workload when using true-right and true-left
      manipulation. CONCLUSIONS: This study objectively assessed SSL performance and
      current attempts for instrumentation improvement in single-site access. While SSL
      significantly impairs basic laparoscopic skills, surgical platforms providing
      true-left and true-right maneuvering of instruments appear to be more intuitive
      and address some of the current challenges of SSL that may otherwise limit its
      widespread acceptance.

PMID- 21193331
TI  - One thousand bedside percutaneous tracheostomies in the surgical intensive care
      unit: time to change the gold standard.
AB  - BACKGROUND: Bedside percutaneous tracheostomy (BPT) is a cost-effective
      alternative to open tracheostomy. Small series have consistently documented
      minimal morbidity, but BPT has yet to be embraced as the standard of care.
      Because this has been our preferred technique in the surgical ICU for more than
      20 years, we reviewed our experience to ascertain its safety. We hypothesize that
      BPT has acceptably minimal morbidity, even in high-risk patients. STUDY DESIGN:
      Patients undergoing BPT from January 1998 to June 2008 were reviewed. High-risk
      patients were defined as those with cervical collar or halo, cervical spine
      injuries, systemic heparinization, positive end-expiratory pressure >10 cm H(2)O
      or fraction of inspired oxygen > 50%. RESULTS: During the study period, 1,000
      patients underwent BPT (74% men; mean +/- SEM age 46 +/- 0.6 years; 70% trauma).
      BPT was performed 8.9 +/- 0.2 days (mean +/- SEM) after admission. Patients
      remained ventilator dependent for an additional 9.7 +/- 0.4 days (mean +/- SEM).
      There were 482 (48%) patients undergoing BPT who were considered high-risk: 1
      risk category, 273 patients; 2 risk categories, 139 patients; 3 risk categories,
      56 patients; 4 risk categories, 12 patients; 5 risk categories, 2 patients.
      Complications occurred in 14 (1.4%) patients. Early complications included
      tracheostomy tube misplacement requiring revision (n = 4), bleeding requiring
      intervention (n = 2), infection (n = 1), and procedure failure requiring
      cricothyroidotomy (n = 1). Late complications included persistent stoma requiring
      operative closure (n = 4) and subglottic stenosis (n = 2). There were 6
      complications (1.2%) in normal risk and 8 complications (1.7%) in high-risk
      patients. There were no deaths related to BPT. CONCLUSIONS: BPT in the surgical
      intensive care unit is a safe procedure, even in high-risk patients. We believe
      BPT is the new gold standard for patients requiring tracheostomy for mechanical
      ventilation.

PMID- 21193332
TI  - A critical evaluation of the impact of Leapfrog's evidence-based hospital
      referral.
AB  - BACKGROUND: Evidence-based hospital referral (EBHR) is a Leapfrog group quality
      metric based primarily on hospital procedural volume. It has yet to be determined
      if EBHR has led to regionalized surgical care and whether it has improved patient
      outcomes. STUDY DESIGN: We conducted a before and after cohort study of 13,157
      adults (1994 to 2007) who underwent pancreatic or esophageal resection or
      abdominal aortic aneurysm (AAA) repair in Washington State. Adjusted mortality,
      readmission, and complication rates were assessed before and after EBHR was
      introduced. RESULTS: Hospitals meeting an EBHR volume metric in any year ranged
      from 2 to 6. Comparing before and after 2001 (2004 for pancreatic resection), the
      proportion of patients treated at hospitals meeting the EBHR volume metric for a
      given procedure increased for pancreatic (59.4% vs 75.7%, p < 0.001) and
      esophageal resection (41.5% vs 59.2%, p < 0.001), but was similar for AAA repair
      (16.3% vs 17.6%, p = 0.13). In general, rates of adverse events were lower at
      hospitals meeting an EBHR volume metric. However, across Washington State and at
      non-EBHR centers, rates of mortality, readmission, and complications generally
      did not improve in the 7 years after introduction of the EBHR initiative.
      CONCLUSIONS: Although a greater proportion of pancreatic or esophageal resections
      were performed at hospitals meeting a given EBHR volume metric in the 7 years
      after Leapfrog, this shift had a negligible impact on outcomes across Washington
      State. It remains to be determined why regionalization for AAA repair has not
      occurred and why regionalization trends in pancreatic and esophageal surgery have
      not had the intended impact of improving overall safety outcomes.

PMID- 21193333
TI  - In vitro study of variables relevant to perioperative care of the surgical
      patient: glucose, osmolarity, and rewarming.
AB  - BACKGROUND: We sought to determine the effects of altering osmolarity and the
      reversibility of the detrimental immunologic effects of hypothermia on human
      monocyte HLA-DR surface expression and reactive oxygen species (ROS) formation.
      STUDY DESIGN: The effects of altering osmolarity on HLA-DR surface expression and
      ROS formation were assessed using lipopolysaccharide (LPS)-treated samples
      treated with either saline, glucose, or mannitol, incubated at 37 degrees C for 2
      hours. HLA-DR surface receptor expression and ROS formation were determined after
      incubation. The effects of the reversibility of hypothermia were measured by
      incubating LPS-treated samples at 34 degrees C, 37 degrees C, and 40 degrees C
      for 1 hour. The samples were subsequently rewarmed at 40 degrees C for 1 and 2
      hours. The effects of rewarming on HLA-DR surface receptor expression and ROS
      formation were reassessed. RESULTS: In the osmolarity experiments, there was a
      49% decrease in ROS formation in samples treated with mannitol as compared with
      saline and glucose. Alterations of osmolarity had no significant effect on HLA-DR
      surface expression. In the rewarming experiments, rewarming for either 1 or 2
      hours abolished any significant differences in HLA-DR surface expression and ROS
      formation between samples preincubated at the different temperatures.
      CONCLUSIONS: The presumed inert mannitol was found to significantly decrease ROS
      formation, but had no effect on HLA-DR surface expression. In addition, the
      effects of hypothermia on HLA-DR surface expression or ROS formation may be
      better reversed within 2 hours than in 1 hour.

PMID- 21193334
TI  - Noninvasive quantitative assessment of synovial pannus angiogenesis by contrast
      enhanced gray-scale sonography in antigen-induced arthritis in rabbits.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to evaluate the value of
      contrast-enhanced gray-scale sonography in quantitative assessment of synovial
      pannus angiogenesis in antigen-induced arthritis in rabbits. MATERIALS AND
      METHODS: Twenty-four adult New Zealand White rabbits were divided into two
      groups. Inflammatory arthritis was induced by intra-articular injection of
      ovalbumin into right knee joints with 4 mg in low-dose group (LD, n = 12) and 8
      mg in high-dose group (HD, n = 12). The left side of the knee on each rabbit was
      used as normal control. Contrast-enhanced gray-scale sonography with time
      intensity curve (TIC) was performed on the synovia of suprapatellar bursa and
      posterior capsules 4 weeks after the injection. Immunohistochemical examinations
      of synovia were applied to assess the microvessel density and the expression of
      vascular endothelial growth factor. Correlation analysis between sonographic and
      immunohistochemical findings was performed. RESULTS: Contrast-enhanced gray-scale
      sonography of all right knees demonstrated intra-articular hypoechoic lesions
      with enhanced blood flow and no abnormal findings on all left knees. Parameters
      of TIC, including ascending curve (A), derived peak intensity (DPI), and area
      under curve (AUC) on arthritis joints were significantly higher in HD group
      compared to LD group (P < .05). Positive correlation was found between
      immunohistochemical findings and parameters of A, DPI, and AUC (P < .05).
      However, no correlation was found between other parameters (slope of descending
      rate, time to peak, time to rise, and initial intensity) and immunohistochemical
      findings. CONCLUSIONS: Contrast-enhanced gray-scale sonography with TIC
      measurement could provide reliable method for noninvasive quantitative assessment
      of synovial pannus angiogenesis of arthritis in clinical settings.

PMID- 21193335
TI  - Feasibility and satisfaction with a tailored web-based audit intervention for
      recalibrating radiologists' thresholds for conducting additional work-up.
AB  - RATIONALE AND OBJECTIVES: To examine the feasibility of and satisfaction with a
      tailored web-based intervention designed to decrease radiologists' recommendation
      of inappropriate additional work-up after a screening mammogram. MATERIALS AND
      METHODS: We developed a web-based educational intervention designed to reduce
      inappropriate recall. Radiologists were randomly assigned to participate in an
      early intervention group or a late (control) intervention group, the latter of
      which served as a control for a 9-month follow-up period, after which they were
      invited to participate in the intervention. Intervention content was derived from
      our prior research and included three modules: 1) an introduction to audit
      statistics for mammography performance; 2) a review of data showing radiologists'
      inflated perceptions of medical malpractice risks related to breast imaging, and
      3) a review of data on breast cancer risk among women seen in their practices.
      Embedded within the intervention were individualized audit data for each
      participating radiologists obtained from the national Breast Cancer Surveillance
      Consortium. RESULTS: Seventy-four radiologists (37.8%; 74/196) consented to the
      intervention, which was completed by 67.5% (27/40) of those randomized to the
      early intervention group and 41.2% (14/34) of those randomized to the late
      (control) group. Thus, a total of 41 (55%) completed the intervention. On
      average, three log-ins were used to complete the program (range 1-14), which took
      approximately 1 hour. Ninety-five percent found the program moderately to very
      helpful in understanding how to calculate basic performance measures. Ninety
      three percent found viewing their own performance measures moderately to very
      helpful, and 83% reported it being moderately to very important to learn that the
      breast cancer risk in their screening population program was lower than
      perceived. The percentage of radiologists who reported that the risk of medical
      malpractice influences their recall rates dropped from 36.3% preintervention to
      17.8% after intervention with a similar drop in perceived influence of
      malpractice risk on their recommendations for breast biopsy (36.4 to 17.3%). More
      than 75% of radiologists answered the postintervention knowledge questions
      correctly, and the percent of time spent in breast imaging did not appear to
      influence responses. The majority (>92%) of participants correctly responded that
      the target recall rate in the United States is 9%. The mean self-reported recall
      rates were 13.0 for radiologists spending <40% time in breast imaging and 14.9%
      for those spending >40% time spent in breast imaging, which was highly correlated
      with their actual recall rates (0.991; P < .001). CONCLUSIONS: Radiologists who
      begin an internet-based tailored intervention designed to help reduce unnecessary
      recall will likely complete it, although only 55% who consented to the study
      actually undertook the intervention. Participants found the program useful in
      helping them understand why their recall rates may be elevated.

PMID- 21193336
TI  - Comments regarding 'sizing fenestrated aortic stent-grafts'.

PMID- 21193338
TI  - Coexistence of beta-thalassemia and polycythemia vera.

PMID- 21193337
TI  - T-cell-pre-stimulated monocytes promote neovascularisation in a murine hind limb
      ischaemia model.
AB  - AIM: Monocytes play a significant role in neovascularisation. The stimuli that
      differentiate monocytes along a pro-angio-/arteriogenic-supporting pathway are
      currently unclear. We investigated whether pre-stimulation of human monocytes
      with soluble T-cell-derived factors improves revascularisation in murine hind
      limb ischaemia as a new option for therapeutic angio- and arteriogenesis. DESIGN:
      Human monocytes were cultured with or without soluble T-cell-derived factors.
      Unstimulated and pre-stimulated monocytes were transfused after induction of hind
      limb ischaemia in nude mice. METHODS: Blood flow was measured with laser Doppler
      perfusion imaging. Collaterals were visualised by immunohistochemistry and
      angiography. Monocytes were characterised by flowcytometry and Bio-Plex assays.
      RESULTS: Transfusion of T-cell-pre-stimulated monocytes significantly improved
      blood flow recovery after hind limb ischaemia and increased collateral size and
      collateral and capillary number in the post-ischaemic paw. Pre-stimulated
      monocytes produced a wide variety of factors that support neovascularisation such
      as platelet-derived growth factor-BB, vascular-endothelial growth factor,
      interleukin-4 and tumour necrosis factor-alpha. Few transfused human cells were
      detected in the muscle tissue, suggesting that paracrine rather than direct
      effects appear responsible for the enhanced recovery of blood flow observed.
      CONCLUSION: These results show a beneficial role for T-cell-pre-stimulated
      monocytes in neovascularisation, rendering the monocyte a potential candidate for
      regenerative cell therapy that promotes revascularisation in peripheral arterial
      disease patients.

PMID- 21193339
TI  - Impact of rotavirus vaccination on childhood deaths from diarrhea in Brazil.
AB  - OBJECTIVES: Rotavirus vaccination was introduced in Brazil in March 2006,
      targeting an annual birth cohort of approximately 3.5 million. We analyzed trends
      in all-cause gastroenteritis-related deaths in children <5 years of age during
      the pre- and post-vaccination periods. METHODS: Data from the National
      Immunization Program and the Mortality Information System were used to calculate
      vaccine coverage and mortality rates related to gastroenteritis in children <1
      year and 1-4 years of age, using population estimates from the census as the
      denominator. Relative reductions in mortality rates were calculated for 2007 and
      2008, using the 2004-2005 mean as baseline before vaccine introduction. RESULTS:
      Coverage of two doses of human rotavirus vaccine was 39% in 2006, increasing to
      72% in 2007 and 77% in 2008. During 2004-2005, the gastroenteritis mortality rate
      in children <1 year of age was 56.9 per 100 000, decreasing by 30% (95%
      confidence interval (CI) 19-41) in 2007 and by 39% (95% CI 29-49) in 2008. In
      children 1-4 years of age, the mortality rate was 4.5 per 100 000 during 2004
      2005, decreasing by 29% (95% CI 10-49) in 2007 and by 33% (95% CI 15-52) in 2008.
      CONCLUSIONS: The decreased rates of childhood gastroenteritis-related deaths in
      Brazil following rotavirus vaccine introduction, particularly among children <1
      year of age, suggest the potential benefit of vaccination.

PMID- 21193340
TI  - Comments on the manuscript by Bitam et al., 'Fleas and flea-borne diseases'.

PMID- 21193342
TI  - WITHDRAWN: Sonochemical three-component synthesis of pyrazolotriazoles.
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- 21193341
TI  - Ethnic differences in weight gain and diabetes risk: the Multiethnic Cohort
      Study.
AB  - AIM: To improve our understanding of excess body weight and risk for diabetes
      type 2, the study examined the influence of weight change in the Hawaii
      component, including 78,006 Caucasians, Japanese Americans and Native Hawaiians,
      of the Multiethnic Cohort Study. METHODS: Participants aged 58.5+/-9.2 years
      completed a questionnaire at cohort entry (Qx1), including weight at age 21, and
      a follow-up questionnaire 5 years later (Qx2). After 14 years of follow-up, 8892
      incident diabetes cases were identified through self-reports or linkups with the
      major health plans in Hawaii. Cox regression analysis was applied, stratified by
      age and adjusted for confounders, to estimate hazard ratios (HRs). RESULTS: The
      mean weight gain from age 21 to Qx1 was 10.5+/-11.0 kg and, between Qx1 and Qx2,
      0.8+/-5.6 kg. Diabetes risk showed a significant dose-response relationship with
      weight gain from age 21 (P<0.0001). The respective HRs for a weight gain of 5-10
      kg and greater or equal to 25 kg were 1.8 (95% CI: 1.7-2.0) and 7.7 (95% CI: 7.1
      8.4), while weight loss of greater than 5 kg significantly reduced diabetes risk
      (HR=0.7; 95% CI: 0.6-0.9). The interaction term of weight change since age 21
      with ethnicity was also highly significant (P<0.0001). Compared with stable
      weight Caucasians, the adverse effects of weight gain were more pronounced in
      those of Japanese and Native Hawaiian descent. Weight change between Qx1 and Qx2
      conferred a smaller risk. CONCLUSION: These findings support the current public
      health recommendations for weight control and particularly among ethnic groups at
      high risk for diabetes.

PMID- 21193343
TI  - Memantine for non-motor features of Parkinson's disease: a double-blind placebo
      controlled exploratory pilot trial.
AB  - OBJECT: To perform an exploratory study evaluating memantine for several common
      non-motor problems in Parkinson's disease. METHODS: We conducted a single center,
      double-blind, placebo controlled pilot trial of memantine, titrated to 20 mg/day,
      in PD subjects. Inclusion criteria were intentionally broad and included both
      fluctuating and non-fluctuating patients. After baseline assessments, subjects (N
      = 40) were randomized to drug and placebo groups. They received a battery of
      traditional and non-motor assessments. After a safety call (2 weeks after
      baseline) they returned for identical assessments at week 8. An 8-week open label
      extension was started if desired. RESULTS: Subject demographics (age 69.1 +/-
      7.8; 24 males), were similar in the drug and placebo groups. Four dropped from
      the study while on drug vs. none on placebo. Two of 36 remaining dropped out over
      the 8-week open label section. Of the 34 who completed the final open label
      visit, 24 elected to be prescribed memantine after the study. During the
      controlled trial, there was no significant change in UPDRS section I or II,
      Epworth sleepiness scale, fatigue severity scale, Hamilton depression scale,
      Conner adult inventory, PD Quality of Life-39, or clinical global impressions.
      UPDRS "on" motor scores tended to improved, p = 0.19. CONCLUSION: Memantine was
      well tolerated in PD; however, specific measures of sleepiness, fatigue,
      depression, and attention did not significantly improve. The majority of subjects
      elected to stay on the drug after the open label extension suggesting some
      unassessed benefit.

PMID- 21193344
TI  - Synthesis and spectral studies of copper complexes using a N-octylated bis
      benzimidazole diamide ligand.
AB  - Monomeric Cu(II) and Cu(I) complexes bound to a tetradentate bis-benzimidazole
      diamide ligand N,N'-bis(N-octyl benzimidazolyl-2yl)(methyl)pentane diamide (O
      GBGA) have been isolated and characterized. X-Band EPR spectra of the copper(II)
      complexes in CH2Cl2 were recorded in a frozen solution as solvent at liquid
      nitrogen temperature. Solution spectra typically indicate a d(x2-y2) ground state
      (g||>g?>2.0023) and show less than four nuclear hyperfine lines with broadening
      of g? line in some cases, thus indicating distorted tetragonal geometry. One of
      the copper(II) complexes shows a five line N-SHF structure (16+/-1G) implying the
      binding of imine nitrogen of the benzimidazole to copper ion. alpha2 ranges from
      0.57-0.97 indicating considerable amount of covalent character in Cu-L bond.
      Anodic shifts in E1/2 values indicate the retention of anion in the coordination
      sphere of Cu(II), E1/2 values becoming anodic in the order C6H5COO-<SCN-<Cl-. The
      fluorescence quantum yield of complexes was found to be lower than that of the
      ligand O-GBGA (Phi=0.029) and the relative fluorescence data reveals that
      fluorescence of such compounds could distinguish between small and large anions.

PMID- 21193345
TI  - Constitutive expression of a peanut ubiquitin-conjugating enzyme gene in
      Arabidopsis confers improved water-stress tolerance through regulation of stress
      responsive gene expression.
AB  - Ubiquitin (Ub)-conjugating enzymes (UBCs) are key enzymes involved in
      ubiquitination. Although UBCs have been shown to play important roles in
      regulating various aspects of plant growth and development, the role of plant
      UBCs in abiotic stress response needs to be examined further. Here we report the
      characterization of a ubiquitin-conjugating enzyme gene AhUBC2 from dehydrated
      peanut plants. The expression of AhUBC2 gene in peanut plants is responsive to
      physiological water-stress induced by polyethylene glycol (PEG6000), high
      salinity, abscisic acid (ABA) or low temperature. The constitutive expression of
      AhUBC2 gene in wild-type Arabidopsis confers improved tolerance to water-stress
      induced by sorbitol or soil drought in 35S::AhUBC2 transgenic plants.
      Constitutive expression of AhUBC2 results in significantly increased expressions
      of three stress-responsive genes P5CS1, RD29A and KIN1 in 35S::AhUBC2 Arabidopsis
      grown under normal conditions, whereas the expressions of other four stress
      responsive genes NCED3, ABF3, RD29B and RD22 are not affected. The proline level
      in 35S::AhUBC2 Arabidopsis is significantly higher than that in wild-type
      Arabidopsis under both soil-drought stressed and control conditions. In contrast,
      there is no significant difference in the levels of NCED3 transcript and
      endogenous ABA between wild-type and 35S::AhUBC2 Arabidopsis. These results
      suggest that constitutive expression of AhUBC2 in Arabidopsis confers improved
      water-stress tolerance likely through activating an ABA-independent signaling
      pathway, including regulating the expression of ABA-independent stress-responsive
      genes and promoting the synthesis of osmolyte proline to protect plants from
      water deficit.

PMID- 21193346
TI  - Loss of Aspergillus oryzae amyR function indirectly affects hemicellulolytic and
      cellulolytic enzyme production.
AB  - Aspergillus oryzae AB390, a derivative of A. oryzae OR101, was found to be
      suitable for soy sauce production, yielding a product light brown in color.
      Compared to the parent strain, hemicellulase and cellulase activities in the
      mutant were higher; however, its amylase activity was found to be much lower. To
      determine the cause of these differences, the enzymatic profile change, as a
      function of the carbon source in submerged cultures, was examined. Amylase
      activity in AB390 was hardly detectable and not affected by the carbon source
      utilized. In the absence of starch where glucose could not be generated,
      hemicellulase and cellulase activities in both the parent and mutant were the
      same. A nonsense mutation was found in the upstream region of the putative
      transactivation domain of the transcriptional activator of the amylolytic genes,
      amyR in AB390. Complementation of AB390 with the wild-type amyR reduced
      hemicellulase and cellulase activities and increased amylase activity in soy
      sauce koji, the mold responsible for giving soy sauce. Northern analysis and two
      dimensional (2-D) electrophoresis indicated that the unique enzymatic profile of
      AB390 was regulated transcriptionally. The results suggested that the loss of
      amyR function indirectly affected the production of hemicellulolytic and
      cellulolytic enzymes, likely through a carbon catabolite repression-mediated
      control.

PMID- 21193347
TI  - Genotypic and phenotypic characterization of Pseudomonas aeruginosa isolates from
      urinary tract infections.
AB  - Pseudomonas aeruginosa is one of the most frequent agents of urinary tract
      infections especially in patients with indwelling urethral catheters. A total of
      30 P. aeruginosa isolates from urinary tract infections was investigated for
      their genotypic and phenotypic characteristics. 'Single Nucleotide Polymorphism'
      chip typing experiments in combination with bioinformatical cluster analyses
      allowed genotypic grouping of the isolates. Some similarities to strains from
      lung infections but also to environmental strains were observed. Finally, several
      urinary tract-specific groups were identified indicating a strong heterogeneity
      of the urethral isolates. Pyoverdin, protease, and phospholipase A production in
      combination with quorum sensing activity and biofilm formation were common
      phenotypic characteristics of these strains. In contrast, swarming phenotypes,
      the production of pyocyanin, and the extracellular enzymes phospholipase C and
      elastase were rarely observed. Interestingly, strains isolated from catheter
      associated infections showed significantly enhanced biofilm formation, decreased
      motility, and a slightly increased expression of virulence factors in relation to
      isolates from acute urinary tract infections.

PMID- 21193349
TI  - How standard is 'standard care' in the symptom management of patients with lung
      cancer? The example of the 'respiratory distress' symptom cluster.

PMID- 21193348
TI  - Methicillin-susceptible Staphylococcus aureus from clinical and community sources
      are genetically diverse.
AB  - Despite the association of methicillin-susceptible S. aureus (MSSA) with several
      life-threatening diseases, relatively little is known about their clinical
      epidemiology in Malaysia. We characterized MSSA isolates (n=252) obtained from
      clinical and community (carriage) sources based on spa sequencing and multilocus
      sequence typing (MLST). The prevalence of several important virulence genes was
      determined to further define the molecular characteristics of MSSA clones
      circulating in Malaysia. Among the 142 clinical and 110 community-acquired MSSA
      isolates, 98 different spa types were identified, corresponding to 8 different
      spa clonal clusters (spa-CCs). In addition, MLST analysis revealed 22 sequence
      types (STs) with 5 singletons corresponding to 12 MLST-CCs. Interestingly, spa
      CC084/085 (MLST-CC15) (p=0.038), spa-non-founder 2 (MLST-ST188) (p=0.002), and
      spa-CC127 (MLST-CC1) (p=0.049) were identified significantly more often among
      clinical isolates. spa-CC3204 (MLST-CC121) (p=0.02) and spa-CC015 (MLST-CC45)
      (p=0.0002) were more common among community isolates. Five dominant MLST-CCs
      (CC8, CC121, CC1, CC45, and CC5) having clear counterparts among the major MRSA
      clones were also identified in this study. While the MSSA strains are usually
      genetically heterogeneous, a relatively high frequency (19/7.5%) of ST188 (t189)
      strains was found, with 57.8% of these strains carrying the Panton-Valentine
      leukocidin (PVL). Analysis of additional virulence genes showed a frequency of
      36.5% and 36.9% for seg and sei and 0.8% and 6.3% for etb and tst genes,
      respectively. Arginine catabolic mobile element (ACME) was detected in 4
      community isolates only. These represent the first isolates harbouring this gene
      in an Asian region. In conclusion, MSSA from the Malaysian community and their
      clinical counterparts are genetically diverse, but certain clones occur more
      often among clinical isolates than among carriage isolates and vice versa.

PMID- 21193350
TI  - Visual paired-associate learning: in search of material-specific effects in adult
      patients who have undergone temporal lobectomy.
AB  - The mesial temporal lobes are important for learning arbitrary associations. It
      has previously been demonstrated that left mesial temporal structures are
      involved in learning word pairs, but it is not yet known whether comparable
      lesions in the right temporal lobe impair visually mediated associative learning.
      Patients who had undergone left (n=16) or right (n=18) temporal lobectomy for
      relief of intractable epilepsy and healthy controls (n=13) were administered two
      paired-associate learning tasks assessing their learning and memory of pairs of
      abstract designs or pairs of symbols in unique locations. Both patient groups had
      deficits in learning the designs, but only the right temporal group was impaired
      in recognition. For the symbol location task, differences were not found in
      learning, but again a recognition deficit was found for the right temporal group.
      The findings implicate the mesial temporal structures in relational learning.
      They support a material-specific effect for recognition but not for learning and
      recall of arbitrary visual and visual-spatial associative information.

PMID- 21193351
TI  - Ocular manifestations of multiple myeloma: three cases and a review of the
      literature.
AB  - BACKGROUND: Multiple myeloma is the most common plasma cell tumor; however,
      ocular plasmacytomas are rare and can appear in almost any structure of the eye.
      We present 3 cases, including 2 with unique ophthalmic ultrasound images of
      ocular plasmacytoma. CASE REPORTS: Three patients with ocular manifestations of
      multiple myeloma are described. All were noted to have known synchronous systemic
      disease. In this study, patients presented with epibulbar (n = 2), iridociliary
      (n = 1), and orbital (n = 2) plasmacytomas. Presenting signs included clinically
      visible tumor (n = 2), blurred vision (n = 2), diplopia (n = 2), and glaucoma (n
      = 1). The iridociliary plasmacytoma was defined by high-frequency 35-MHz
      ultrasonography that revealed 360 degrees  of anterior chamber involvement,
      secondary angle-closure, and extent of iridociliary invasion. In another case,
      low-frequency B-scan ultrasonography found multiple myeloma of the orbit. Ocular
      manifestations of multiple myeloma, histopathology, treatment, and prognosis are
      described. CONCLUSION: Ocular manifestations of plasma cell neoplasms are rare.
      In multiple myeloma, plasmacytomas can present as a solitary tumor, as an initial
      sign of systemic disease, or as recurrence. This study presents 3 cases in which
      epibulbar, orbital, and iridociliary plasmacytoma with secondary glaucoma were
      presenting signs of uncontrolled multiple myeloma.

PMID- 21193353
TI  - Meningioma of the conus medullaris mimicking neurofibroma--possibly radiation
      induced.
AB  - BACKGROUND CONTEXT: Radiation-induced meningiomas (RIMs) of the brain are the
      most common RIMs. However, there has been no report in the literature of an RIM
      of the spine. Conus medullaris is a favorite site for ependymomas, whereas it is
      an extremely rare location for meningiomas. Dumbbell-shaped configuration is
      typical for nerve sheath tumors; however, it is very rarely seen in meningiomas.
      PURPOSE: To describe imaging findings of a possibly RIM at the level of the conus
      medullaris mimicking a neurofibroma. STUDY DESIGN: A 60-year-old male with 6-year
      history of irradiated urinary bladder cancer presented with paraparesis. METHODS:
      Radiography, computed tomography, and magnetic resonance imaging of the
      thoracolumbar spine were undertaken. RESULTS: Radiography showed widening of
      intervertebral foramina at T12-L1 level. Computed tomography and magnetic
      resonance imaging disclosed a lobulated intradural mass at the level of the conus
      medullaris causing widening and scalloping of adjacent bony structures, with
      dumbbell-shaped configuration. Surgical biopsy of the mass was consistent with
      fibroblastic meningioma. CONCLUSIONS: The reported tumor might have developed
      secondary to irradiation for urinary bladder cancer because meningiomas are the
      most common radiation-induced central nervous system tumors. Although location at
      the level of the conus medullaris is atypical for meningioma, and dumbbell-shaped
      configuration is rather characteristic for neurogenic tumors, they should not
      exclude a diagnosis of meningioma.

PMID- 21193352
TI  - Repeated vertebrobasilar thromboembolism in a patient with severe upper cervical
      instability because of rheumatoid arthritis.
AB  - BACKGROUND CONTEXT: Although many reports have examined upper cervical rheumatoid
      arthritis (RA) and spinal cord disorders resulting from RA lesions, few cases of
      thromboembolic events in the vertebrobasilar system associated with RA lesions of
      the upper cervical spine have been reported. PURPOSE: We encountered a rare case
      of repeated vertebrobasilar thromboembolism with severe upper cervical
      instability resulting from RA. Furthermore, we obtained clinical images of the
      vertebrobasilar system just before and after the first thromboembolic event. We
      thus present the case of a patient with RA who recovered without surgery from
      repeated vertebrobasilar thromboembolism that might have been caused by severe
      upper cervical instability. STUDY DESIGN: Case report. METHODS: A 59-year-old man
      with a 14-year history of RA experienced nuchal pain because of severe
      atlantoaxial and vertical subluxations. While awaiting surgery, he developed left
      Wallenberg syndrome because of occlusion in the left vertebral artery (VA). Five
      days later, he displayed impaired consciousness and symptoms of right Wallenberg
      syndrome. Emergency magnetic resonance angiography showed occlusion in the
      basilar artery. After thrombolytic therapy, he gradually recovered. RESULTS:
      Because we presumed that the patient's recurrent thrombus formation resulted from
      kinking of the right VA caused by severe instability of the upper cervical spine,
      we planned to treat him surgically despite his impaired consciousness and
      tracheostomy. However, the anesthesiologist would not approve surgery because the
      patient had high-risk conditions. The cervical spine was thus realigned and
      immobilized in a halo apparatus for 3 months to achieve stability. Now, more than
      5 years after these events, the patient has experienced no more thromboembolic
      events and his condition has remained stable, without need for surgery.
      CONCLUSIONS: Repeated vertebrobasilar thromboembolism in patients with RA may
      sometimes be caused by severe upper cervical instability that can be treated
      without surgery.

PMID- 21193354
TI  - Unusual image of a herniated lumbar disc.

PMID- 21193356
TI  - Looks can be deceiving: dissociation between angiographic severity and
      hemodynamic significance of a lesion. The importance of microvascular resistance.
AB  - We present a case of an intermediate right coronary artery lesion with a
      fractional flow reserve (FFR) of 0.93 despite a myocardial perfusion scan
      demonstrating reversible ischemia in the inferior wall. An assessment of
      microvascular resistance was performed using the index of microcirculatory
      resistance (IMR). This was consistent with elevated resistance and may explain
      the discordance between the high FFR result, the positive perfusion study, and
      the lesion appearance on angiography. FFR assumes stable and minimal resistance
      at hyperemia; however, there may be situations where this does not occur,
      contributing to discrepant values. An understanding of the underlying
      physiological principles that underpin FFR is required for all physicians using
      this increasingly utilized technique.

PMID- 21193355
TI  - Should the organs at risk be contoured in vaginal cuff brachytherapy?
AB  - PURPOSE: To assess the dose to the organs at risk (OARs) and utility of repeated
      OAR dose-volume histogram calculations in multifraction high-dose-rate vaginal
      cylinder brachytherapy using 3-dimensional imaging. METHODS AND MATERIALS: Thirty
      eight patients (125 fractions) received high-dose-rate brachytherapy to the
      vaginal vault between January 2005 and October 2005. All patients emptied their
      bladders before insertion. After each insertion, a CT scan with 2.5-mm slices and
      contours of the bladder, rectum, and sigmoid was performed. Dose-volume
      histograms were generated for the D(0.1cc) and D(2cc) for the OAR using a
      software program created at our institution. Variance component models estimated
      the within-patient variance of the dose to the OAR between fractions. Predictors
      of dose to the OAR were identified using linear mixed models. RESULTS: The within
      patient coefficients of variation of total D(0.1cc) dose were bladder 14.0%,
      rectum 7.9%, and sigmoid 27.6%; for D(2cc), these were 8.1%, 5.9%, and 20.3%,
      respectively. Intraclass correlations ranged from 0.27 to 0.79. Larger OAR
      predicted greater total D(0.1cc) and D(2cc). Other predictors of total D(0.1cc)
      and D(2cc) dose included the size of the cylinder and the length of the treatment
      field for rectum. CONCLUSIONS: CT simulation provides a noninvasive assessment of
      the dose to the bladder, rectum, and sigmoid. The small within-patient variation
      in doses to the bladder and rectum do not support reporting doses to the OARs
      beyond the initial fraction.

PMID- 21193357
TI  - Schizosaccharomyces pombe encodes a mutated AP endonuclease 1.
AB  - Mutagenic and cytotoxic apurinic/apyrimidinic (AP) sites are among the most
      frequent lesions in DNA. Repair of AP sites is initiated by AP endonucleases and
      most organisms possess two or more of these enzymes. Saccharomyces cerevisiae has
      AP endonuclease 1 (Apn1) as the major enzymatic activity with AP endonuclease 2
      (Apn2) being an important backup. Schizosaccharomyces pombe also encodes two
      potential AP endonucleases, and Apn2 has been found to be the main repair
      activity, while Apn1 has no, or only a limited role in AP site repair. Here we
      have identified a new 5' exon (exon 1) in the apn1 gene and show that the
      inactivity of S. pombe Apn1 is due to a nonsense mutation in the fifth codon of
      this new exon. Reversion of this mutation restored the AP endonuclease activity
      of S. pombe Apn1. Interestingly, the apn1 nonsense mutation was only found in
      laboratory strains derived from L972 h(-) and not in unrelated isolates of S.
      pombe. Since all S. pombe laboratory strains originate from L972 h(-), it appears
      that all experiments involving S. pombe have been conducted in an apn1(-) mutant
      strain with a corresponding DNA repair deficiency. These observations have
      implications both for future research in S. pombe and for the interpretation of
      previously conducted epistatis analysis.

PMID- 21193358
TI  - Isolated post-transplantation lymphoproliferative disorder of the esophagus.

PMID- 21193359
TI  - Zollinger-Ellison syndrome: presentation, response to therapy, and outcome.
AB  - BACKGROUND: Recent series describing the clinical presentation, response to
      therapy, and long-term outcome of Zollinger-Ellison syndrome are limited. AIMS:
      To assess the clinical characteristics and long-term outcome of patients with
      Zollinger-Ellison syndrome. METHODS: Over a 20-year period, patients with
      Zollinger-Ellison syndrome were enrolled in a prospective trial evaluating the
      efficacy of lansoprazole. Following dose stabilization, patients were followed on
      a 6-monthly basis with interval history, physical examination, endoscopy with
      gastric biopsies, gastric acid analysis and laboratory studies. RESULTS: 72
      patients (mean age 54+/-12 years, % male 58%, % Caucasian 69%) were prospectively
      enrolled. The clinical presentation was stereotypical for Zollinger-Ellison
      syndrome. Symptoms had been reported for a median of 9 years prior to diagnosis.
      Cross-sectional abdominal imaging was often negative for demonstrable tumour. All
      patients had gastric acid hypersecretion controlled with variable doses of
      lansoprazole (median dose 60 mg/day, range 15-480 mg/day). The median survival
      from the time of diagnosis was 6.6 years; only two of 19 deaths were due to
      metastatic gastrinoma. CONCLUSIONS: The clinical presentation of Zollinger
      Ellison syndrome was similar to prior reports. Acid hypersecretion was controlled
      in all patients with variable doses of lansoprazole. Long-term survival was
      principally related to underlying co-morbidity.

PMID- 21193360
TI  - [In memoriam: Prof. Dr. Juan Rodriguez Soriano (1933-2010)].

PMID- 21193361
TI  - Vitamin E--an aid to wound healing?

PMID- 21193362
TI  - Do the findings of the Term Breech Trial apply to spontaneous breech birth?

PMID- 21193363
TI  - CYP17 gene polymorphism and prostate cancer susceptibility in a Tunisian
      population.
AB  - Prostate cancer (PCa) formation has been reported to be associated with androgen.
      Two key steps in the sex steroid synthesis are mediated by the enzyme cytochrome
      P450c 17alpha which is encoded in the CYP17 gene. The A2 allele of the CYP17 gene
      has been thought to be associated with increased functional activity of this
      steroidogenic enzyme. Consequently, the A2 allele has been examined as a
      biomarker of individual susceptibility to hormone-related diseases among men. We
      prospectively assessed the association between the A2 allele of CYP17 and PCa
      risk among 125 cases and 125 controls in a case-control study. Our aim was to
      investigate whether a polymorphism of CYP17 gene could be used as a genetic
      marker for associating PCa. The result revealed a significant association between
      the CYP17 polymorphic genotypes and PCa. Therefore, CYP17 gene polymorphism is
      likely contributed to the pathogenesis of PCa but not to disease severity.

PMID- 21193364
TI  - Cytogenetic and comparative genomic hybridization study of Indian myelodysplastic
      syndromes.
AB  - INTRODUCTION: Myelodysplastic syndromes (MDSs) are clonal stem cell disorders
      characterized by cytopenias, dysplasia in one or more cell lineages and
      ineffective hematopoiesis and are associated with significant morbidity and
      mortality due to bone marrow failure or evolution to acute myeloid leukemia.
      Clonal chromosomal abnormalities are detected in 40-60% of patients. Multiple
      recurrent chromosomal aberrations have been identified by cytogenetics including
      fluorescence in situ hybridization (FISH) which is now widely recognized as one
      of the most important diagnostic and prognostic markers in MDS. METHODS:
      Conventional cytogenetics by GTG-banding, FISH, comparative genomic hybridization
      (CGH) was done on 40 primary MDS subjects. RESULTS: Among 40 subjects, 10 (25%)
      were abnormal and 30 (75%) showed apparently normal karyotypes with GTG banding
      and FISH. The various aberrations observed were del 5q-, del 7q-, 20q-, +8. DNA
      copy number changes including losses (30%) and gains (20%) were detected by CGH
      in 11 (36.6%) out of 30 karyotypically normal MDS. However chromosome 7 (37%) and
      1 (25%) is frequently involved in current study population. CONCLUSIONS: This
      study confirms that the apart from non-random chromosome aberrations, other
      chromosome regions also involved in the MDS development. The occupational,
      environmental and geographical variations might be influencing the disease.
      Furthermore cytogenetic studies are warranted in larger groups of MDS cases to
      identify newly acquired chromosome aberrations that may aid in cloning new genes
      involved in the neoplastic process, ultimately helping in the development of
      targeted therapeutic drugs.

PMID- 21193366
TI  - Odor discrimination using neural decoding of the main olfactory bulb in rats.
AB  - This paper presents a novel method for inferring the odor based on neural
      activities observed from rats' main olfactory bulbs. Multichannel extracellular
      single unit recordings were done by microwire electrodes (tungsten, 50 MUm, 32
      channels) implanted in the mitral/tufted cell layers of the main olfactory bulb
      of anesthetized rats to obtain neural responses to various odors. Neural response
      as a key feature was measured by subtraction of neural firing rate before
      stimulus from after. For odor inference, we have developed a decoding method
      based on the maximum likelihood estimation. The results have shown that the
      average decoding accuracy is about 100.0%, 96.0%, 84.0%, and 100.0% with four
      rats, respectively.

PMID- 21193368
TI  - Theoretical and experimental analysis of electroporated membrane conductance in
      cell suspension.
AB  - An intense electric field can be applied to increase the membrane conductance
      G(m) and consequently, the conductivity of cell suspension. This phenomenon is
      called electroporation. This mechanism is used in a wide range of medical
      applications, genetic engineering, and therapies. Conductivity measurements of
      cell suspensions were carried out during application of electric fields from 40
      to 165 kV/m. Experimental results were analyzed with two electroporation models:
      the asymptotic electroporation model was used to estimate G(m) at the beginning
      and at the end of electric field pulse, and the extended Kinosita electroporation
      model to increase G(m) linearly in time. The maximum G(m) was 1-7 * 10(4) S/m(2),
      and the critical angle (when the G(m) is insignificant) was 50 degrees -65
      degrees . In addition, the sensitivity of electroporated membrane conductance to
      extracellular and cytoplasmatic conductivity and cell radius has been studied.
      This study showed that external conductivity and cell radius are important
      parameters affecting the pore-opening phenomenon. However, if the cell radius is
      larger than 7 MUm in low conductivity medium, the cell dimensions are not so
      important.

PMID- 21193367
TI  - Overcoming endogenous constraints on neuronal regeneration.
AB  - One of the grand challenges in neuroengineering is to stimulate regeneration
      after central nervous system (CNS) or peripheral nervous system (PNS) injury to
      restore function. The state of the art today is that PNS injuries heal to a
      limited extent, whereas CNS injuries are largely intractable to regeneration. In
      this context, we examine the underlying biochemical and cellular constraints on
      endogenous healing of neural tissues. Identification and characterization of
      endogenous "rate-limiting" processes that constrain regeneration would allow one
      to craft solutions to overcome critical impediments for accelerated healing. It
      is increasingly evident that biochemical pathways triggered by the nature and
      duration of injury-triggered inflammatory response may determine the endogenous
      constraints and subsequently determine regenerative fate. In this paper, critical
      endogenous constraints of PNS and CNS regeneration are identified, and the
      effects of modulating the phenotypes of immune cells on neuronal regeneration are
      discussed.

PMID- 21193369
TI  - Addressing neurological disorders with neuromodulation.
AB  - Neurological disorders are becoming increasingly common in developed countries as
      a result of the aging population. In spite of medications, these disorders can
      result in progressive loss of function as well as chronic physical, cognitive,
      and emotional disability that ultimately places enormous emotional and economic
      on the patient, caretakers, and the society in general. Neuromodulation is
      emerging as a therapeutic option in these patients. Neuromodulation is a field,
      which involves implantable devices that allow for the reversible adjustable
      application of electrical, chemical, or biological agents to the central or
      peripheral nervous system with the objective of altering its functioning with the
      objective of achieving a therapeutic or clinically beneficial effect. It is a
      rapidly evolving field that brings together many different specialties in the
      fields of medicine, materials science, computer science and technology,
      biomedical, and neural engineering as well as the surgical or interventional
      specialties. It has multiple current and emerging indications, and an enormous
      potential for growth. The main challenges before it are in the need for effective
      collaboration between engineers, basic scientists, and clinicians to develop
      innovations that address specific problems resulting in new devices and clinical
      applications.

PMID- 21193370
TI  - Accounting for phase drifts in SSVEP-based BCIs by means of biphasic stimulation.
AB  - This study proposes a novel biphasic stimulation technique to solve the issue of
      phase drifts in steady-state visual evoked potential (SSVEPs) in phase-tagged
      systems. Phase calibration was embedded in stimulus sequences using a biphasic
      flicker, which is driven by a sequence with alternating reference and phase-shift
      states. Nine subjects were recruited to participate in off-line and online tests.
      Signals were bandpass filtered and segmented by trigger signals into reference
      and phase-shift epochs. Frequency components of SSVEP in the reference and phase
      shift epochs were extracted using the Fourier method with a 50% overlapped
      sliding window. The real and imaginary parts of the SSVEP frequency components
      were organized into complex vectors in each epoch. Hotelling's t-square test was
      used to determine the significances of nonzero mean vectors. The rejection of
      noisy data segments and the validation of gaze detections were made based on p
      values. The phase difference between the valid mean vectors of reference and
      phase-shift epochs was used to identify user's gazed targets in this system. Data
      showed an average information transfer rate of 44.55 and 38.21 bits/min in off
      line and online tests, respectively.

PMID- 21193371
TI  - Novel dry polymer foam electrodes for long-term EEG measurement.
AB  - A novel dry foam-based electrode for long-term EEG measurement was proposed in
      this study. In general, the conventional wet electrodes are most frequently used
      for EEG measurement. However, they require skin preparation and conduction gels
      to reduce the skin-electrode contact impedance. The aforementioned procedures
      when wet electrodes were used usually make trouble to users easily. In order to
      overcome the aforesaid issues, a novel dry foam electrode, fabricated by
      electrically conductive polymer foam covered by a conductive fabric, was
      proposed. By using conductive fabric, which provides partly polarizable electric
      characteristic, our dry foam electrode exhibits both polarization and
      conductivity, and can be used to measure biopotentials without skin preparation
      and conduction gel. In addition, the foam substrate of our dry electrode allows a
      high geometric conformity between the electrode and irregular scalp surface to
      maintain low skin-electrode interface impedance, even under motion. The
      experimental results presented that the dry foam electrode performs better for
      long-term EEG measurement, and is practicable for daily life applications.

PMID- 21193372
TI  - Quantification of restitution dispersion from the dynamic changes of the T-wave
      peak to end, measured at the surface ECG.
AB  - Action potential duration restitution (APDR) curves present spatial variations
      due to the electrophysiological heterogeneities present in the heart. Enhanced
      spatial APDR dispersion in ventricle has been suggested as an arrhythmic risk
      marker. In this study, we propose a method to noninvasively quantify dispersion
      of APDR slopes at tissue level by making only use of the surface
      electrocardiogram (ECG). The proposed estimate accounts for rate normalized
      differences in the steady-state T-wave peak to T-wave end interval (T(pe)). A
      methodology is developed for its computation, which includes compensation for the
      T(pe) memory lag after heart-rate (HR) changes. The capability of the proposed
      estimate to reflect APDR dispersion is assessed using a combination of ECG signal
      processing, and computational modeling and simulation. Specifically, ECG
      recordings of control subjects undergoing a tilt test trial are used to measure
      that estimate, while its capability to provide a quantification of APDR
      dispersion at tissue level is assessed by using a 2-D ventricular tissue
      simulation. From this simulation, APDR dispersion, denoted as ?alpha(SIM), is
      calculated, and pseudo-ECGs are derived. Estimates of APDR dispersion measured
      from the pseudo-ECGs show to correlate with ?alpha(SIM), being the mean relative
      error below 5%. A comparison of the ECG estimates obtained from tilt test
      recordings and the ?alpha(SIM) values measured in silico simulations at tissue
      level show that differences between them are below 20 % , which is within
      physiological variability limits. Our results provide evidence that the proposed
      estimate is a noninvasive measurement of APDR dispersion in ventricle. Additional
      results from this study confirm that T(pe) adapts to HR changes much faster than
      the QT interval.

PMID- 21193373
TI  - Principal curve algorithms for partitioning high-dimensional data spaces.
AB  - Most partitioning algorithms iteratively partition a space into cells that
      contain underlying linear or nonlinear structures using linear partitioning
      strategies. The compactness of each cell depends on how well the (locally) linear
      partitioning strategy approximates the intrinsic structure. To partition a
      compact structure for complex data in a nonlinear context, this paper proposes a
      nonlinear partition strategy. This is a principal curve tree (PC-tree), which is
      implemented iteratively. Given that a PC passes through the middle of the data
      distribution, it allows for partitioning based on the arc length of the PC. To
      enhance the partitioning of a given space, a residual version of the PC-tree
      algorithm is developed, denoted here as the principal component analysis tree
      (PCR-tree) algorithm. Because of its residual property, the PCR-tree can yield
      the intrinsic dimension of high-dimensional data. Comparisons presented in this
      paper confirm that the proposed PC-tree and PCR-tree approaches show a better
      performance than several other competing partitioning algorithms in terms of
      vector quantization error and nearest neighbor search. The comparison also shows
      that the proposed algorithms outperform competing linear methods in total average
      coverage which measures the nonlinear compactness of partitioning algorithms.

PMID- 21193374
TI  - Uniformly stable backpropagation algorithm to train a feedforward neural network.
AB  - Neural networks (NNs) have numerous applications to online processes, but the
      problem of stability is rarely discussed. This is an extremely important issue
      because, if the stability of a solution is not guaranteed, the equipment that is
      being used can be damaged, which can also cause serious accidents. It is true
      that in some research papers this problem has been considered, but this concerns
      continuous-time NN only. At the same time, there are many systems that are better
      described in the discrete time domain such as population of animals, the annual
      expenses in an industry, the interest earned by a bank, or the prediction of the
      distribution of loads stored every hour in a warehouse. Therefore, it is of
      paramount importance to consider the stability of the discrete-time NN. This
      paper makes several important contributions. 1) A theorem is stated and proven
      which guarantees uniform stability of a general discrete-time system. 2) It is
      proven that the backpropagation (BP) algorithm with a new time-varying rate is
      uniformly stable for online identification and the identification error converges
      to a small zone bounded by the uncertainty. 3) It is proven that the weights'
      error is bounded by the initial weights' error, i.e., overfitting is eliminated
      in the proposed algorithm. 4) The BP algorithm is applied to predict the
      distribution of loads that a transelevator receives from a trailer and places in
      the deposits in a warehouse every hour, so that the deposits in the warehouse are
      reserved in advance using the prediction results. 5) The BP algorithm is compared
      with the recursive least square (RLS) algorithm and with the Takagi-Sugeno type
      fuzzy inference system in the problem of predicting the distribution of loads in
      a warehouse, giving that the first and the second are stable and the third is
      unstable. 6) The BP algorithm is compared with the RLS algorithm and with the
      Kalman filter algorithm in a synthetic example.

PMID- 21193375
TI  - A majorize-minimize strategy for subspace optimization applied to image
      restoration.
AB  - This paper proposes accelerated subspace optimization methods in the context of
      image restoration. Subspace optimization methods belong to the class of iterative
      descent algorithms for unconstrained optimization. At each iteration of such
      methods, a stepsize vector allowing the best combination of several search
      directions is computed through a multidimensional search. It is usually obtained
      by an inner iterative second-order method ruled by a stopping criterion that
      guarantees the convergence of the outer algorithm. As an alternative, we propose
      an original multidimensional search strategy based on the majorize-minimize
      principle. It leads to a closed-form stepsize formula that ensures the
      convergence of the subspace algorithm whatever the number of inner iterations.
      The practical efficiency of the proposed scheme is illustrated in the context of
      edge-preserving image restoration.

PMID- 21193376
TI  - Contextual kernel and spectral methods for learning the semantics of images.
AB  - This paper presents contextual kernel and spectral methods for learning the
      semantics of images that allow us to automatically annotate an image with
      keywords. First, to exploit the context of visual words within images for
      automatic image annotation, we define a novel spatial string kernel to quantify
      the similarity between images. Specifically, we represent each image as a 2-D
      sequence of visual words and measure the similarity between two 2-D sequences
      using the shared occurrences of s -length 1-D subsequences by decomposing each 2
      D sequence into two orthogonal 1-D sequences. Based on our proposed spatial
      string kernel, we further formulate automatic image annotation as a contextual
      keyword propagation problem, which can be solved very efficiently by linear
      programming. Unlike the traditional relevance models that treat each keyword
      independently, the proposed contextual kernel method for keyword propagation
      takes into account the semantic context of annotation keywords and propagates
      multiple keywords simultaneously. Significantly, this type of semantic context
      can also be incorporated into spectral embedding for refining the annotations of
      images predicted by keyword propagation. Experiments on three standard image
      datasets demonstrate that our contextual kernel and spectral methods can achieve
      significantly better results than the state of the art.

PMID- 21193377
TI  - Image decomposition with multilabel context: algorithms and applications.
AB  - Most research on image decomposition, e.g., image segmentation and image parsing,
      has predominantly focused on the low-level visual clues within a single image and
      neglected the contextual information across images. In this paper, we present a
      new perspective to image decomposition piloted by the multilabel context
      associated with each individual image. Observing that the contextual information
      (i.e., local label representations of the same label are similar while those from
      different labels are dissimilar) exists across images, we propose to perform
      image decomposition in a collective way and obtain an optimal representation for
      each label from a set of multilabeled images. We formulate the problem as an
      optimization problem which maximizes inter-label difference while minimizing the
      intra-label difference of the target label representations and propose two ways
      to solve this problem. Such a contextual image decomposition has a wide variety
      of applications, among which two exemplary ones-multilabel image annotation and
      label ranking, are presented and evaluated with different classification
      techniques. Extensive experiments on two benchmark datasets demonstrate promising
      results.

PMID- 21193378
TI  - Nonlocal PDEs-based morphology on weighted graphs for image and data processing.
AB  - Mathematical morphology (MM) offers a wide range of operators to address various
      image processing problems. These operators can be defined in terms of algebraic
      (discrete) sets or as partial differential equations (PDEs). In this paper, we
      introduce a nonlocal PDEs-based morphological framework defined on weighted
      graphs. We present and analyze a set of operators that leads to a family of
      discretized morphological PDEs on weighted graphs. Our formulation introduces
      nonlocal patch-based configurations for image processing and extends PDEs-based
      approach to the processing of arbitrary data such as nonuniform high dimensional
      data. Finally, we show the potentialities of our methodology in order to process,
      segment and classify images and arbitrary data.

PMID- 21193379
TI  - 3-D active meshes: fast discrete deformable models for cell tracking in 3-D time
      lapse microscopy.
AB  - Variational deformable models have proven over the past decades a high efficiency
      for segmentation and tracking in 2-D sequences. Yet, their application to 3-D
      time-lapse images has been hampered by discretization issues, heavy computational
      loads and lack of proper user visualization and interaction, limiting their use
      for routine analysis of large data-sets. We propose here to address these
      limitations by reformulating the problem entirely in the discrete domain using 3
      D active meshes, which express a surface as a discrete triangular mesh, and
      minimize the energy functional accordingly. By performing computations in the
      discrete domain, computational costs are drastically reduced, whilst the mesh
      formalism allows to benefit from real-time 3-D rendering and other GPU-based
      optimizations. Performance evaluations on both simulated and real biological data
      sets show that this novel framework outperforms current state-of-the-art methods,
      constituting a light and fast alternative to traditional variational models for
      segmentation and tracking applications.

PMID- 21193380
TI  - On random transformations for changeable face verification.
AB  - The generation of changeable and privacy-preserving biometric templates is
      important for the pervasive deployment of biometric technology in a wide variety
      of applications. This paper presents a systematic analysis of random
      transformation-based methods for addressing the changeability and privacy
      problems in biometrics-based verification systems. The proposed methods transform
      the original biometric feature vectors using random transformations, and the
      sorted index numbers (SIN) of the resulting vectors in the transformed domain are
      stored as the biometric templates. Three types of random transformations, namely,
      random additive transform, random multiplicative transform, and random
      projection, are discussed and analyzed. The random transformations, in
      combination with the SIN approach, constitute repeatable and noninvertible
      transformations; hence, the generated templates are changeable and provide
      privacy protection. The effectiveness of the proposed methods is well supported
      by both detailed analysis and extensive experimentation on a face verification
      problem.

PMID- 21193381
TI  - Face image modeling by multilinear subspace analysis with missing values.
AB  - Multilinear subspace analysis (MSA) is a promising methodology for pattern
      recognition problems due to its ability in decomposing the data formed from the
      interaction of multiple factors. The MSA requires a large training set, which is
      well organized in a single tensor, which consists of data samples with all
      possible combinations of the contributory factors. However, such a "complete"
      training set is difficult (or impossible) to obtain in many real applications.
      The missing-value problem is therefore crucial to the practicality of the MSA but
      has been hardly investigated up to present. To solve the problem, this paper
      proposes an algorithm named M(2)SA, which is advantageous in real applications
      due to the following: 1) it inherits the ability of the MSA to decompose the
      interlaced semantic factors; 2) it does not depend on any assumptions on the data
      distribution; and 3) it can deal with a high percentage of missing values. M(2)SA
      is evaluated by face image modeling on two typical multifactorial applications,
      i.e., face recognition and facial age estimation. Experimental results show the
      effectiveness of M(2) SA even when the majority of the values in the training
      tensor are missing.

PMID- 21193382
TI  - Development of a model osseo-magnetic link for intuitive rotational control of
      upper-limb prostheses.
AB  - The lack of proprioceptive feedback is a serious deficiency of current prosthetic
      control systems. The Osseo-Magnetic Link (OML) is a novel humeral or wrist
      rotation control system that could preserve proprioception. It utilizes a magnet
      implanted within the residual bone and sensors mounted in the prosthetic socket
      to detect magnetic field vectors and determine the bone's orientation. This
      allows the use of volitional bone rotation to control a prosthetic rotator. We
      evaluated the performance of the OML using a physical model of a transhumeral
      residual limb. A small Neodymium-Iron-Boron magnet was placed in a model humerus,
      inside a model upper arm. Four three-axis Hall-effect sensors were mounted on a
      ring 3 cm distal to the magnet. An optimization algorithm based on Newton's
      method determined the position and orientation of the magnet within the model
      humerus under various conditions, including bone translations, interference, and
      magnet misalignment. The orientation of the model humerus was determined within 3
      degrees  for rotations centered in the arm; an additional 6 degrees  error was
      found for translations 20 mm from center. Adjustments in sensor placement may
      reduce these errors. The results demonstrate that the OML is a feasible solution
      for providing prosthesis rotation control while preserving rotational
      proprioception.

PMID- 21193383
TI  - Determining the optimal window length for pattern recognition-based myoelectric
      control: balancing the competing effects of classification error and controller
      delay.
AB  - Pattern recognition-based control of myoelectric prostheses has shown great
      promise in research environments, but has not been optimized for use in a
      clinical setting. To explore the relationship between classification error,
      controller delay, and real-time controllability, 13 able-bodied subjects were
      trained to operate a virtual upper-limb prosthesis using pattern recognition of
      electromyogram (EMG) signals. Classification error and controller delay were
      varied by training different classifiers with a variety of analysis window
      lengths ranging from 50 to 550 ms and either two or four EMG input channels.
      Offline analysis showed that classification error decreased with longer window
      lengths (p < 0.01 ). Real-time controllability was evaluated with the target
      achievement control (TAC) test, which prompted users to maneuver the virtual
      prosthesis into various target postures. The results indicated that user
      performance improved with lower classification error (p < 0.01 ) and was reduced
      with longer controller delay (p < 0.01 ), as determined by the window length.
      Therefore, both of these effects should be considered when choosing a window
      length; it may be beneficial to increase the window length if this results in a
      reduced classification error, despite the corresponding increase in controller
      delay. For the system employed in this study, the optimal window length was found
      to be between 150 and 250 ms, which is within acceptable controller delays for
      conventional multistate amplitude controllers.

PMID- 21193384
TI  - Toward a quantitative estimate of future heat wave mortality under global climate
      change.
AB  - BACKGROUND: Climate change is anticipated to affect human health by changing the
      distribution of known risk factors. Heat waves have had debilitating effects on
      human mortality, and global climate models predict an increase in the frequency
      and severity of heat waves. The extent to which climate change will harm human
      health through changes in the distribution of heat waves and the sources of
      uncertainty in estimating these effects have not been studied extensively.
      OBJECTIVES: We estimated the future excess mortality attributable to heat waves
      under global climate change for a major U.S. city. METHODS: We used a database
      comprising daily data from 1987 through 2005 on mortality from all nonaccidental
      causes, ambient levels of particulate matter and ozone, temperature, and dew
      point temperature for the city of Chicago, Illinois. We estimated the
      associations between heat waves and mortality in Chicago using Poisson regression
      models. RESULTS: Under three different climate change scenarios for 2081-2100 and
      in the absence of adaptation, the city of Chicago could experience between 166
      and 2,217 excess deaths per year attributable to heat waves, based on estimates
      from seven global climate models. We noted considerable variability in the
      projections of annual heat wave mortality; the largest source of variation was
      the choice of climate model. CONCLUSIONS: The impact of future heat waves on
      human health will likely be profound, and significant gains can be expected by
      lowering future carbon dioxide emissions.

PMID- 21193385
TI  - A comparison of different approaches to estimate small-scale spatial variation in
      outdoor NO2 concentrations.
AB  - BACKGROUND: In epidemiological studies, small-scale spatial variation in air
      quality is estimated using land-use regression (LUR) and dispersion models. An
      important issue of exposure modeling is the predictive performance of the model
      at unmeasured locations. OBJECTIVE: In this study, we aimed to evaluate the
      performance of two LUR models (large area and city specific) and a dispersion
      model in estimating small-scale variations in nitrogen dioxide (NO2)
      concentrations. METHODS: Two LUR models were developed based on independent NO2
      monitoring campaigns performed in Amsterdam and in a larger area including
      Amsterdam, the Netherlands, in 2006 and 2007, respectively. The measurement data
      of the other campaign were used to evaluate each model. Predictions from both LUR
      models and the calculation of air pollution from road traffic (CAR) dispersion
      model were compared against NO2 measurements obtained from Amsterdam. RESULTS AND
      CONCLUSION: The large-area and the city-specific LUR models provided good
      predictions of NO2 concentrations [percentage of explained variation (R2) = 87%
      and 72%, respectively]. The models explained less variability of the
      concentrations in the other sampling campaign, probably related to differences in
      site selection, and illustrated the need to select sampling sites representative
      of the locations to which the model will be applied. More complete traffic
      information contributed more to a better model fit than did detailed land-use
      data. Dispersion-model estimates for NO2 concentrations were within the range of
      both LUR estimates.

PMID- 21193386
TI  - Pleural mesothelioma in New Caledonia: associations with environmental risk
      factors.
AB  - BACKGROUND: High incidences of malignant mesothelioma (MM) have been observed in
      New Caledonia. Previous work has shown an association between MM and soil
      containing serpentinite. OBJECTIVES: We studied the spatial and temporal
      variation of MM and its association with environmental factors. METHODS: We
      investigated the 109 MM cases recorded in the Cancer Registry of New Caledonia
      between 1984 and 2008 and performed spatial, temporal, and space-time cluster
      analyses. We conducted an ecological analysis involving 100 tribes over a large
      area including those with the highest incidence rates. Associations with
      environmental factors were assessed using logistic and Poisson regression
      analyses. RESULTS: The highest incidence was observed in the Houailou area with a
      world age-standardized rate of 128.7 per 100,000 person-years [95% confidence
      interval (CI), 70.41-137.84]. A significant spatial cluster grouped 18 tribes (31
      observed cases vs. 8 expected cases; p = 0.001), but no significant temporal
      clusters were identified. The ecological analyses identified serpentinite on
      roads as the greatest environmental risk factor (odds ratio = 495.0; 95% CI, 46.2
      4679.7; multivariate incidence rate ratio = 13.0; 95% CI, 10.2-16.6). The risk
      increased with serpentinite surface, proximity to serpentinite quarries and
      distance to the peridotite massif. The association with serpentines was stronger
      than with amphiboles. Living on a slope and close to dense vegetation appeared
      protective. The use of whitewash, previously suggested to be a risk factor, was
      not associated with MM incidence. CONCLUSIONS: Presence of serpentinite on roads
      is a major environmental risk factor for mesothelioma in New Caledonia.

PMID- 21193387
TI  - Time-series analysis of mortality effects of fine particulate matter components
      in Detroit and Seattle.
AB  - BACKGROUND: Recent toxicological and epidemiological studies have shown
      associations between particulate matter (PM) and adverse health effects, but
      which PM components are most influential is less well known. OBJECTIVES: In this
      study, we used time-series analyses to determine the associations between daily
      fine PM [PM <= 2.5 um in aerodynamic diameter (PM2.5)] concentrations and daily
      mortality in two U.S. cities-Seattle, Washington, and Detroit, Michigan. METHODS:
      We obtained daily PM2.5 filters for the years of 2002-2004 and analyzed trace
      elements using X-ray fluorescence and black carbon using light reflectance as a
      surrogate measure of elemental carbon. We used Poisson regression and distributed
      lag models to estimate excess deaths for all causes and for cardiovascular and
      respiratory diseases adjusting for time-varying covariates. We computed the
      excess risks for interquartile range increases of each pollutant at lags of 0
      through 3 days for both warm and cold seasons. RESULTS: The cardiovascular and
      respiratory mortality series exhibited different source and seasonal patterns in
      each city. The PM2.5 components and gaseous pollutants associated with mortality
      in Detroit were most associated with warm season secondary aerosols and traffic
      markers. In Seattle, the component species most closely associated with mortality
      included those for cold season traffic and other combustion sources, such as
      residual oil and wood burning. CONCLUSIONS: The effects of PM2.5 on daily
      mortality vary with source, season, and locale, consistent with the hypothesis
      that PM composition has an appreciable influence on the health effects
      attributable to PM.

PMID- 21193388
TI  - Involvement of N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) in arsenic
      biomethylation and its role in arsenic-induced toxicity.
AB  - BACKGROUND: In humans, inorganic arsenic (iAs) is metabolized to methylated
      arsenical species in a multistep process mainly mediated by arsenic (+3 oxidation
      state) methyltransferase (AS3MT). Among these metabolites is monomethylarsonous
      acid (MMAIII), the most toxic arsenic species. A recent study in As3mt-knockout
      mice suggests that unidentified methyltransferases could be involved in
      alternative iAs methylation pathways. We found that yeast deletion mutants
      lacking MTQ2 were highly resistant to iAs exposure. The human ortholog of the
      yeast MTQ2 is N-6 adenine-specific DNA methyltransferase 1 (N6AMT1), encoding a
      putative methyltransferase. OBJECTIVE: We investigated the potential role of
      N6AMT1 in arsenic-induced toxicity. METHODS: We measured and compared the
      cytotoxicity induced by arsenicals and their metabolic profiles using inductively
      coupled plasma-mass spectrometry in UROtsa human urothelial cells with enhanced
      N6AMT1 expression and UROtsa vector control cells treated with different
      concentrations of either iAsIII or MMAIII. RESULTS: N6AMT1 was able to convert
      MMAIII to the less toxic dimethylarsonic acid (DMA) when overexpressed in UROtsa
      cells. The enhanced expression of N6AMT1 in UROtsa cells decreased cytotoxicity
      of both iAsIII and MMAIII. Moreover, N6AMT1 is expressed in many human tissues at
      variable levels, although at levels lower than those of AS3MT, supporting a
      potential participation in arsenic metabolism in vivo. CONCLUSIONS: Considering
      that MMAIII is the most toxic arsenical, our data suggest that N6AMT1 has a
      significant role in determining susceptibility to arsenic toxicity and
      carcinogenicity because of its specific activity in methylating MMAIII to DMA and
      other unknown mechanisms.

PMID- 21193389
TI  - Secondary storage of dermatan sulfate in Sanfilippo disease.
AB  - Mucopolysaccharidoses are a group of genetically inherited disorders that result
      from the defective activity of lysosomal enzymes involved in glycosaminoglycan
      catabolism, causing their intralysosomal accumulation. Sanfilippo disease
      describes a subset of mucopolysaccharidoses resulting from defects in heparan
      sulfate catabolism. Sanfilippo disorders cause severe neuropathology in affected
      children. The reason for such extensive central nervous system dysfunction is
      unresolved, but it may be associated with the secondary accumulation of
      metabolites such as gangliosides. In this article, we describe the accumulation
      of dermatan sulfate as a novel secondary metabolite in Sanfilippo. Based on
      chondroitinase ABC digestion, chondroitin/dermatan sulfate levels in fibroblasts
      from Sanfilippo patients were elevated 2-5-fold above wild-type dermal
      fibroblasts. Lysosomal turnover of chondroitin/dermatan sulfate in these cell
      lines was significantly impaired but could be normalized by reducing heparan
      sulfate storage using enzyme replacement therapy. Examination of
      chondroitin/dermatan sulfate catabolic enzymes showed that heparan sulfate and
      heparin can inhibit iduronate 2-sulfatase. Analysis of the chondroitin/dermatan
      sulfate fraction by chondroitinase ACII digestion showed dermatan sulfate
      storage, consistent with inhibition of iduronate 2-sulfatase. The discovery of a
      novel storage metabolite in Sanfilippo patients may have important implications
      for diagnosis and understanding disease pathology.

PMID- 21193390
TI  - Fibulin-5 is up-regulated by hypoxia in endothelial cells through a hypoxia
      inducible factor-1 (HIF-1alpha)-dependent mechanism.
AB  - Hypoxia modulates gene expression and affects multiple aspects of endothelial
      cell biology. Fibulin-5 (FBLN5) is an extracellular matrix protein essential for
      elastic fiber assembly and vasculogenesis that participates in vascular
      remodeling and controls endothelial cell adhesion, motility, and proliferation.
      In this context, we aimed to analyze FBLN5 regulation by hypoxia in endothelial
      cells. Hypoxia (1% O(2)) increased FBLN5 mRNA levels in endothelial cells in a
      time-dependent manner. Maximal induction (~2.5-fold) was achieved after 24 h of
      hypoxia. This effect paralleled an increase in both intracellular and
      extracellular FBLN5 protein levels. The increase in FBLN5 mRNA levels observed in
      hypoxic cells was blocked by inhibitors of the PI3K/Akt/mTOR pathway (LY294002
      and rapamycin) and mimicked by dimethyl oxal glycine, which prevents proline
      hydroxylase-mediated degradation of HIF-1alpha. Silencing of HIF-1alpha
      completely prevented hypoxia-induced FBLN5 up-regulation. Accordingly, both
      hypoxia and HIF-1alpha overexpression increased FBLN5 transcriptional activity.
      Serial promoter deletion and mutagenesis studies revealed the involvement of a
      putative hypoxia response element (HRE) located at -78 bp. In fact, EMSA and ChIP
      assays demonstrated increased HIF-1 binding to this site in hypoxic cells.
      Interestingly, the rate of endothelial cells undergoing apoptosis in cultures
      exposed to hypoxia increased in FBLN5 knockdown cells, suggesting that hypoxia
      induced FBLN5 expression contributes to preserve cell survival. These results
      provide evidence that HIF-1 signaling underlies the increase of FBLN5 expression
      elicited by hypoxia in endothelial cells and suggest that FBLN5 induction could
      be involved in the adaptive survival response of endothelial cells to hypoxia.

PMID- 21193391
TI  - Specific and shared targets of ephrin A signaling in epidermal keratinocytes.
AB  - Both ephrins (EFNs) and their receptors (Ephs) are membrane-bound, restricting
      their interactions to the sites of direct cell-to-cell interfaces. They are
      widely expressed, often co-expressed, and regulate developmental processes, cell
      adhesion, motility, survival, proliferation, and differentiation. Both tumor
      suppressor and oncogene activities are ascribed to EFNs and Ephs in various
      contexts. A major conundrum regarding the EFN/Eph system concerns their large
      number and functional redundancy given the promiscuous cross-activation of
      ligands and receptors and the overlapping intracellular signaling pathways. To
      address this issue, we treated human epidermal keratinocytes with five EFNAs
      individually and defined the transcriptional responses in the cells. We found
      that a large set of genes is coregulated by all EFNAs. However, although the
      responses to EFNA3, EFNA4, and EFNA5 are identical, the responses to EFNA1 and
      EFNA2 are characteristic and distinctive. All EFNAs induce epidermal
      differentiation markers and suppress cell adhesion genes, especially integrins.
      Ontological analysis showed that all EFNAs induce cornification and keratin genes
      while suppressing wound healing-associated, signaling, receptor, and
      extracellular matrix-associated genes. Transcriptional targets of AP1 are
      selectively suppressed by EFNAs. EFNA1 and EFNA2, but not the EFNA3, EFNA4, EFNA5
      cluster, regulate the members of the ubiquitin-associated proteolysis genes.
      EFNA1 specifically induces collagen production. Our results demonstrate that the
      EFN-Eph interactions in the epidermis, although promiscuous, are not redundant
      but specific. This suggests that different members of the EFN/Eph system have
      specific, clearly demarcated functions.

PMID- 21193392
TI  - Creating directed double-strand breaks with the Ref protein: a novel RecA
      dependent nuclease from bacteriophage P1.
AB  - The bacteriophage P1-encoded Ref protein enhances RecA-dependent recombination in
      vivo by an unknown mechanism. We demonstrate that Ref is a new type of enzyme;
      that is, a RecA-dependent nuclease. Ref binds to ss- and dsDNA but does not
      cleave any DNA substrate until RecA protein and ATP are added to form RecA
      nucleoprotein filaments. Ref cleaves only where RecA protein is bound. RecA
      functions as a co-nuclease in the Ref/RecA system. Ref nuclease activity can be
      limited to the targeted strands of short RecA-containing D-loops. The result is a
      uniquely programmable endonuclease activity, producing targeted double-strand
      breaks at any chosen DNA sequence in an oligonucleotide-directed fashion. We
      present evidence indicating that cleavage occurs in the RecA filament groove. The
      structure of the Ref protein has been determined to 1.4 A resolution. The core
      structure, consisting of residues 77-186, consists of a central 2-stranded beta
      hairpin that is sandwiched between several alpha-helical and extended loop
      elements. The N-terminal 76 amino acid residues are disordered; this flexible
      region is required for optimal activity. The overall structure of Ref, including
      several putative active site histidine residues, defines a new subclass of HNH
      family nucleases. We propose that enhancement of recombination by Ref reflects
      the introduction of directed, recombinogenic double-strand breaks.

PMID- 21193393
TI  - Hypoxia-inducible factor alpha subunit stabilization by NEDD8 conjugation is
      reactive oxygen species-dependent.
AB  - Hypoxia-inducible factor alpha proteins (HIF-alphas) are regulated oxygen
      dependently and transactivate numerous genes essential for cellular adaptation to
      hypoxia. NEDD8, a member of the ubiquitin-like family, covalently binds to its
      substrate proteins, and thus, regulates their stabilities and functions. In the
      present study, we examined the possibility that the HIF signaling is regulated by
      the neddylation. HIF-1alpha expression and activity were inhibited by knocking
      down APPBP1 E1 enzyme for NEDD8 conjugation but enhanced by ectopically
      expressing NEDD8. HIF-1alpha and HIF-2alpha were identified to be covalently
      modified by NEDD8. NEDD8 stabilized HIF-1alpha even in normoxia and further
      increased its level in hypoxia, which also occurred in von Hippel-Lindau (VHL)
      protein- or p53-null cell lines. The HIF-1alpha-stabilizing effect of NEDD8 was
      diminished by antioxidants and mitochondrial respiratory chain blockers. This
      suggests that the NEDD8 effect is concerned with reactive oxygen species driven
      from mitochondria rather than with the prolyl hydroxylase (PHD)/VHL-dependent
      oxygen-sensing system. Based on these findings, we propose that NEDD8 is an
      ancillary player to regulate the stability of HIF-1alpha. Furthermore, given the
      positive role played by HIF-alphas in cancer promotion, the NEDD8 conjugation
      process could be a potential target for cancer therapy.

PMID- 21193394
TI  - Crystal structure and inhibition studies of transglutaminase from Streptomyces
      mobaraense.
AB  - The crystal structure of the microbial transglutaminase (MTGase) zymogen from
      Streptomyces mobaraense has been determined at 1.9-A resolution using the
      molecular replacement method based on the crystal structure of the mature MTGase.
      The overall structure of this zymogen is similar to that of the mature form,
      consisting of a single disk-like domain with a deep active cleft at the edge of
      the molecule. A major portion of the prosequence (45 additional amino acid
      residues at the N terminus of the mature transglutaminase) folds into an L-shaped
      structure, consisting of an extended N-terminal segment linked with a one-turn
      short helix and a long alpha-helix. Two key residues in the short helix of the
      prosequence, Tyr-12 and Tyr-16, are located on top of the catalytic triad (Cys
      110, Asp-301, and His-320) to block access of the substrate acyl donors and
      acceptors. Biochemical characterization of the mature MTGase, using N-alpha
      benzyloxycarbonyl-L-glutaminylglycine as a substrate, revealed apparent K(m) and
      k(cat)/K(m) values of 52.66 mM and 40.42 mM(-1) min(-1), respectively. Inhibition
      studies using the partial prosequence SYAETYR and homologous sequence SQAETYR
      showed a noncompetitive inhibition mechanism with IC(50) values of 0.75 and 0.65
      mM, respectively, but no cross-linking product formation. Nevertheless, the
      prosequence homologous oligopeptide SQAETQR, with Tyr-12 and Tyr-16 each replaced
      with Gln, exhibited inhibitory activity with the formation of the SQAETQR
      monodansylcadaverine fluorophore cross-linking product (SQAETQR-C-DNS). MALDI-TOF
      tandem MS analysis of SQAETQR-C-DNS revealed molecular masses corresponding to
      those of (N)SQAETQ(C)-C-DNS and C-DNS-(N)QR(C) sequences, suggesting the
      incorporation of C-DNS onto the C-terminal Gln residue of the prosequence
      homologous oligopeptide. These results support the putative functional roles of
      both Tyr residues in substrate binding and inhibition.

PMID- 21193395
TI  - Blocking the gate to ligand entry in human hemoglobin.
AB  - His(E7) to Trp replacements in HbA lead to markedly biphasic bimolecular CO
      rebinding after laser photolysis. For isolated mutant subunits, the fraction of
      fast phase increases with increasing [CO], suggesting a competition between
      binding to an open conformation with an empty E7 channel and relaxation to
      blocked or closed, slowly reacting states. The rate of conformational relaxation
      of the open state is ~18,000 s(-1) in alpha subunits and ~10-fold faster in beta
      subunits, ~175,000 s(-1). Crystal structures were determined for tetrameric
      alpha(WT)beta(Trp-63) HbCO, alpha(Trp-58)beta(WT) deoxyHb, and Trp-64 deoxy- and
      CO-Mb as controls. In Trp-63(E7) betaCO, the indole side chain is located in the
      solvent interface, blocking entry into the E7 channel. Similar blocked Trp-64(E7)
      conformations are observed in the mutant Mb crystal structures. In Trp-58(E7)
      deoxy-alpha subunits, the indole side chain fills both the channel and the distal
      pocket, forming a completely closed state. The bimolecular rate constant for CO
      binding, k'(CO), to the open conformations of both mutant Hb subunits is ~80-90
      MUm(-1) s(-1), whereas k'(CO) for the completely closed states is 1000-fold
      slower, ~0.08 MUm(-1) s(-1). A transient intermediate with k'(CO) ~ 0.7 MUm(-1)
      s(-1) is observed after photolysis of Trp-63(E7) betaCO subunits and indicates
      that the indole ring blocks the entrance to the E7 channel, as observed in the
      crystal structures of Trp(E7) deoxyMb and betaCO subunits. Thus, either blocking
      or completely filling the E7 channel dramatically slows bimolecular binding,
      providing strong evidence that the E7 channel is the major pathway (>=90%) for
      ligand entry in human hemoglobin.

PMID- 21193396
TI  - Distinct allostery induced in the cyclic GMP-binding, cyclic GMP-specific
      phosphodiesterase (PDE5) by cyclic GMP, sildenafil, and metal ions.
AB  - The activity of many proteins orchestrating different biological processes is
      regulated by allostery, where ligand binding at one site alters the function of
      another site. Allosteric changes can be brought about by either a change in the
      dynamics of a protein, or alteration in its mean structure. We have investigated
      the mechanisms of allostery induced by chemically distinct ligands in the cGMP
      binding, cGMP-specific phosphodiesterase, PDE5. PDE5 is the target for catalytic
      site inhibitors, such as sildenafil, that are used for the treatment of erectile
      dysfunction and pulmonary hypertension. PDE5 is a multidomain protein and
      contains two N-terminal cGMP-specific phosphodiesterase, bacterial adenylyl
      cyclase, FhLA transcriptional regulator (GAF) domains, and a C-terminal catalytic
      domain. Cyclic GMP binding to the GAFa domain and sildenafil binding to the
      catalytic domain result in conformational changes, which to date have been
      studied either with individual domains or with purified enzyme. Employing
      intramolecular bioluminescence resonance energy transfer, which can monitor
      conformational changes both in vitro and in intact cells, we show that binding of
      cGMP and sildenafil to PDE5 results in distinct conformations of the protein.
      Metal ions bound to the catalytic site also allosterically modulated cGMP- and
      sildenafil-induced conformational changes. The sildenafil-induced conformational
      change was temperature-sensitive, whereas cGMP-induced conformational change was
      independent of temperature. This indicates that different allosteric ligands can
      regulate the conformation of a multidomain protein by distinct mechanisms.
      Importantly, this novel PDE5 sensor has general physiological and clinical
      relevance because it allows the identification of regulators that can modulate
      PDE5 conformation in vivo.

PMID- 21193397
TI  - The multifunctional Ca2+/calmodulin-dependent kinase II delta (CaMKIIdelta)
      controls neointima formation after carotid ligation and vascular smooth muscle
      cell proliferation through cell cycle regulation by p21.
AB  - The multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)
      promotes vascular smooth muscle (VSMC) proliferation. However, the signaling
      pathways mediating CAMKII-dependent proliferative effects in vivo are poorly
      understood. This study tested the hypothesis that CaMKIIdelta mediates neointimal
      proliferation after carotid artery ligation by regulating expression and activity
      of cell cycle regulators, particularly at the G1/S checkpoint. Data herein
      indicate that 14 days after carotid ligation, C57Bl/6 mice developed a marked
      neointima with robust CaMKII protein expression. In particular, only the CaMKII
      isoform delta was increased as demonstrated by quantitative RT-PCR. Genetic
      deletion of CaMKII delta prevented injury-induced neointimal hyperplasia and cell
      proliferation in the intima and media. In ligated carotids of control mice, the
      proliferative cell cycle markers cdk2, cyclin E, and cyclin D1 were activated. In
      contrast, in CaMKIIdelta(-/-) mice, we detected a reduction in proliferative cell
      cycle regulators as well as an increase in the cell cycle inhibitor p21. This
      expression profile was confirmed in cultured CaMKIIdelta(-/-) VSMC, in which cdk2
      and cdk4 activity was decreased. Toward understanding how CAMKIIdelta affects
      p53, a transcriptional regulator of p21, we examined p53 pathway components. Our
      data indicate that p53 is elevated in CAMKIIdelta(-/-) VSMC, whereas
      phosphorylation of the p53-specific E3 ligase, Mdm2, was decreased. In
      conclusion, CaMKII stimulates neointima proliferation after vascular injury by
      regulating cell proliferation through inhibition of p21 and induction of Mdm-2
      mediated degradation of p53.

PMID- 21193398
TI  - Inhibition of autophagosome formation by the benzoporphyrin derivative
      verteporfin.
AB  - Autophagy enables cells to degrade and recycle cytoplasmic materials both as a
      housekeeping mechanism and in response to extracellular stress such as nutrient
      deprivation. Recent studies indicate that autophagy also functions as a
      protective mechanism in response to several cancer therapy agents, making it a
      prospective therapeutic target. Few pharmacological inhibitors suitable for
      testing the therapeutic potential of autophagy inhibition in vivo are known. An
      automated microscopy assay was used to screen >3,500 drugs and pharmacological
      agents and identified one drug, verteporfin, as an inhibitor of autophagosome
      accumulation. Verteporfin is a benzoporphyrin derivative used in photodynamic
      therapy, but it inhibits autophagy without light activation. Verteporfin did not
      inhibit LC3/Atg8 processing or membrane recruitment in response to autophagic
      stimuli, but it inhibited drug- and starvation-induced autophagic degradation and
      the sequestration of cytoplasmic materials into autophagosomes. Transient
      exposure to verteporfin in starvation conditions reduced cell viability whereas
      cells in nutrient-rich medium were unaffected by drug treatment. Analysis of
      structural analogs indicated that the activity of verteporfin requires the
      presence of a substituted cyclohexadiene at ring A of the porphyrin core but that
      it can tolerate a number of large substituents at rings C and D. The existence of
      an autophagy inhibitor among FDA-approved drugs should facilitate the
      investigation of the therapeutic potential of autophagy inhibition in vivo.

PMID- 21193399
TI  - Competitive modulation of Ca2+ release-activated Ca2+ channel gating by STIM1 and
      2-aminoethyldiphenyl borate.
AB  - Activation of Ca(2+) release-activated Ca(2+) channels by depletion of
      intracellular Ca(2+) stores involves physical interactions between the
      endoplasmic reticulum Ca(2+) sensor, STIM1, and the channels composed of Orai
      subunits. Recent studies indicate that the Orai3 subtype, in addition to being
      store-operated, is also activated in a store-independent manner by 2
      aminoethyldiphenyl borate (2-APB), a small molecule with complex pharmacology.
      However, it is unknown whether the store-dependent and -independent activation
      modes of Orai3 channels operate independently or whether there is cross-talk
      between these activation states. Here we report that in addition to causing
      direct activation, 2-APB also regulates store-operated gating of Orai3 channels,
      causing potentiation at low doses and inhibition at high doses. Inhibition of
      store-operated gating by 2-APB was accompanied by the suppression of several
      modes of Orai3 channel regulation that depend on STIM1, suggesting that high
      doses of 2-APB interrupt STIM1-Orai3 coupling. Conversely, STIM1-bound Orai3 (and
      Orai1) channels resisted direct gating by high doses of 2-APB. The rate of direct
      2-APB activation of Orai3 channels increased linearly with the degree of STIM1
      Orai3 uncoupling, suggesting that 2-APB has to first disengage STIM1 before it
      can directly gate Orai3 channels. Collectively, our results indicate that the
      store-dependent and -independent modes of Ca(2+) release-activated Ca(2+) channel
      activation are mutually exclusive: channels bound to STIM1 resist 2-APB gating,
      whereas 2-APB antagonizes STIM1 gating.

PMID- 21193400
TI  - Reduction of clofazimine by mycobacterial type 2 NADH:quinone oxidoreductase: a
      pathway for the generation of bactericidal levels of reactive oxygen species.
AB  - The mechanism of action of clofazimine (CFZ), an antimycobacterial drug with a
      long history, is not well understood. The present study describes a redox cycling
      pathway that involves the enzymatic reduction of CFZ by NDH-2, the primary
      respiratory chain NADH:quinone oxidoreductase of mycobacteria and nonenzymatic
      oxidation of reduced CFZ by O(2) yielding CFZ and reactive oxygen species (ROS).
      This pathway was demonstrated using isolated membranes and purified recombinant
      NDH-2. The reduction and oxidation of CFZ was measured spectrally, and the
      production of ROS was measured using a coupled assay system with Amplex Red.
      Supporting the ROS-based killing mechanism, bacteria grown in the presence of
      antioxidants are more resistant to CFZ. CFZ-mediated increase in NADH oxidation
      and ROS production were not observed in membranes from three different Gram
      negative bacteria but was observed in Staphylococcus aureus and Saccharomyces
      cerevisiae, which is consistent with the known antimicrobial specificity of CFZ.
      A more soluble analog of CFZ, KS6, was synthesized and was shown to have the same
      activities as CFZ. These studies describe a pathway for a continuous and high
      rate of reactive oxygen species production in Mycobacterium smegmatis treated
      with CFZ and a CFZ analog as well as evidence that cell death produced by these
      agents are related to the production of these radical species.

PMID- 21193401
TI  - The glutamate agonist homocysteine sulfinic acid stimulates glucose uptake
      through the calcium-dependent AMPK-p38 MAPK-protein kinase C zeta pathway in
      skeletal muscle cells.
AB  - Homocysteine sulfinic acid (HCSA) is a homologue of the amino acid cysteine and a
      selective metabotropic glutamate receptor (mGluR) agonist. However, the metabolic
      role of HCSA is poorly understood. In this study, we showed that HCSA and
      glutamate stimulated glucose uptake in C2C12 mouse myoblast cells and increased
      AMP-activated protein kinase (AMPK) phosphorylation. RT-PCR and Western blot
      analysis revealed that C2C12 expresses mGluR5. HCSA transiently increased the
      intracellular calcium concentration. Although alpha-methyl-4
      carboxyphenylglycine, a metabotropic glutamate receptor antagonist, blocked the
      action of HCSA in intracellular calcium response and AMPK phosphorylation, 6
      cyano-7-nitroquinoxaline-2,3-dione, an AMPA antagonist, did not exhibit such
      effects. Knockdown of mGluR5 with siRNA blocked HCSA-induced AMPK
      phosphorylation. Pretreatment of cells with STO-609, a calmodulin-dependent
      protein kinase kinase (CaMKK) inhibitor, blocked HCSA-induced AMPK
      phosphorylation, and knockdown of CaMKK blocked HCSA-induced AMPK
      phosphorylation. In addition, HCSA activated p38 mitogen-activated protein kinase
      (MAPK). Expression of dominant-negative AMPK suppressed HCSA-mediated
      phosphorylation of p38 MAPK, and inhibition of AMPK and p38 MAPK blocked HCSA
      induced glucose uptake. Phosphorylation of protein kinase C zeta (PKCzeta) was
      also increased by HCSA. Pharmacologic inhibition or knockdown of p38 MAPK blocked
      HCSA-induced PKCzeta phosphorylation, and knockdown of PKCzeta suppressed the
      HCSA-induced increase of cell surface GLUT4. The stimulatory effect of HCSA on
      cell surface GLUT4 was impaired in FITC-conjugated PKCzeta siRNA-transfected
      cells. Together, the above results suggest that HCSA may have a beneficial role
      in glucose metabolism in skeletal muscle cells via stimulation of AMPK.

PMID- 21193402
TI  - Tn glycosylation of the MUC6 protein modulates its immunogenicity and promotes
      the induction of Th17-biased T cell responses.
AB  - The Tn antigen (alpha-GalNAc-O-Ser/Thr) is one of the most specific human cancer
      associated structures. This antigen, together with mucins, the major carriers of
      O-glycosylated tumor antigens in adenocarcinomas, are being evaluated as anti
      cancer immunotherapeutic targets. In particular, the MUC6 protein, which is
      normally expressed only in gastric tissues, has been detected in intestinal,
      pulmonary, colorectal, and breast carcinomas. To develop anti-cancer vaccines
      based on the Tn antigen, we produced MUC6 proteins with different Tn density by
      using mixtures of recombinant ppGalNAc-T1, -T2, and -T7. The obtained
      glycoproteins were characterized and analyzed for their immunological properties,
      as compared with the non-glycosylated MUC6. We show that these various MUC6:Tn
      glycoproteins were well recognized by both MUC6 and Tn-specific antibodies.
      However, Tn glycosylation of the MUC6 protein strongly affected their
      immunogenicity by partially abrogating Th1 cell responses, and promoting IL-17
      responses. Moreover, the non-glycosylated MUC6 was more efficiently presented
      than MUC6:Tn glycoproteins to specific T CD4(+) hybridomas, suggesting that Tn
      glycosylation may affect MUC6 processing or MHC binding of the processed
      peptides. In conclusion, our results indicate that Tn glycosylation of the MUC6
      protein strongly affects its B and T cell immunogenicity, and might favor immune
      escape of tumor cells.

PMID- 21193403
TI  - Kre6 protein essential for yeast cell wall beta-1,6-glucan synthesis accumulates
      at sites of polarized growth.
AB  - Saccharomyces cerevisiae Kre6 is a type II membrane protein with amino acid
      sequence homology with glycoside hydrolase and is essential for beta-1,6-glucan
      synthesis as revealed by the mutant phenotype, but its biochemical function is
      still unknown. The localization of Kre6, determined by epitope tagging, is a
      matter of debate. We raised anti-Kre6 rabbit antiserum and examined the
      localization of Kre6 and its tagged protein by immunofluorescence microscopy,
      subcellular fractionation in sucrose density gradients, and immunoelectron
      microscopy. Integration of the results indicates that the majority of Kre6 is in
      the endoplasmic reticulum; however, a small but significant portion is also
      present in the secretory vesicle-like compartments and plasma membrane. Kre6 in
      the latter compartments is observed as strong signals that accumulate at the
      sites of polarized growth by immunofluorescence. The truncated Kre6 without the N
      terminal 230-amino acid cytoplasmic region did not show this polarized
      accumulation and had a severe defect in beta-1,6-glucan synthesis. This is the
      first evidence of a beta-1,6-glucan-related protein showing the polarized
      membrane localization that correlates with its biological function.

PMID- 21193404
TI  - Pulmonary proteases in the cystic fibrosis lung induce interleukin 8 expression
      from bronchial epithelial cells via a heme/meprin/epidermal growth factor
      receptor/Toll-like receptor pathway.
AB  - A high intrapulmonary protease burden is characteristic of cystic fibrosis (CF),
      and the resulting dysregulation of the protease/anti-protease balance has serious
      implications for inflammation in the CF lung. Because of this inflammation, micro
      bleeds can occur releasing hemoglobin into the lung. The aim of this study was to
      investigate the effect of the protease-rich environment of the CF lung on human
      hemoglobin and to assess the proinflammatory effect of heme on CF bronchial
      epithelium. Here, we show that the Pseudomonas proteases (Pseudomonas elastase
      and alkaline protease) and the neutrophil proteases (neutrophil elastase (NE) and
      proteinase-3) are capable of almost complete degradation of hemoglobin in vitro
      but that NE is the predominant protease that cleaves hemoglobin in vivo in CF
      bronchoalveolar lavage fluid. One of the effects of this is the release of heme,
      and in this study we show that heme stimulates IL-8 and IL-10 protein production
      from DeltaF508 CFBE41o(-) bronchial epithelial cells. In addition, heme-induced
      IL-8 expression utilizes a novel pathway involving meprin, EGF receptor, and
      MyD88. Meprin levels are elevated in CF cell lines and bronchial brushings, thus
      adding to the proinflammatory milieu. Interestingly, alpha(1)-antitrypsin, in
      addition to its ability to neutralize NE and protease-3, can also bind heme and
      neutralize heme-induced IL-8 from CFBE41o(-) cells. This study illustrates the
      proinflammatory effects of micro-bleeds in the CF lung, the process by which this
      occurs, and a potential therapeutic intervention.

PMID- 21193405
TI  - Redox regulation of rotation of the cyanobacterial F1-ATPase containing thiol
      regulation switch.
AB  - F(1)-ATP synthase (F(1)-ATPase) is equipped with a special mechanism that
      prevents the wasteful reverse reaction, ATP hydrolysis, when there is
      insufficient proton motive force to drive ATP synthesis. Chloroplast F(1)-ATPase
      is subject to redox regulation, whereby ATP hydrolysis activity is regulated by
      formation and reduction of the disulfide bond located on the gamma subunit. To
      understand the molecular mechanism of this redox regulation, we constructed a
      chimeric F(1) complex (alpha(3)beta(3)gamma(redox)) using cyanobacterial F(1),
      which mimics the regulatory properties of the chloroplast F(1)-ATPase, allowing
      the study of its regulation at the single molecule level. The redox state of the
      gamma subunit did not affect the ATP binding rate to the catalytic site(s) and
      the torque for rotation. However, the long pauses caused by ADP inhibition were
      frequently observed in the oxidized state. In addition, the duration of
      continuous rotation was relatively shorter in the oxidized
      alpha(3)beta(3)gamma(redox) complex. These findings lead us to conclude that
      redox regulation of CF(1)-ATPase is achieved by controlling the probability of
      ADP inhibition via the gamma subunit inserted region, a sequence feature observed
      in both cyanobacterial and chloroplast ATPase gamma subunits, which is important
      for ADP inhibition (Sunamura, E., Konno, H., Imashimizu-Kobayashi, M., Sugano,
      Y., and Hisabori, T. (2010) Plant Cell Physiol. 51, 855-865).

PMID- 21193406
TI  - ESCRT-0 assembles as a heterotetrameric complex on membranes and binds multiple
      ubiquitinylated cargoes simultaneously.
AB  - The ESCRT machinery consists of multiple protein complexes that collectively
      participate in the biogenesis of multivesicular endosomes (MVEs). The ESCRT-0
      complex is composed of two subunits, Hrs and STAM, both of which can engage
      ubiquitinylated substrates destined for lysosomal degradation. Here, we conduct a
      comprehensive analysis of ESCRT-0:ubiquitin interactions using isothermal
      titration calorimetry and define the affinity of each ubiquitin-binding domain
      (UBD) within the intact ESCRT-0 complex. Our data demonstrate that ubiquitin
      binding is non-cooperative between the ESCRT-0 UBDs. Additionally, our findings
      show that the affinity of the Hrs double ubiquitin interacting motif (DUIM) for
      ubiquitin is more than 2-fold greater than that of UBDs found in STAM, suggesting
      that Hrs functions as the major ubiquitin-binding protein in ESCRT-0. In vivo,
      Hrs and STAM localize to endosomal membranes. To study recombinant ESCRT-0
      assembly on lipid bilayers, we used atomic force microscopy. Our data show that
      ESCRT-0 forms mostly heterodimers and heterotetramers of Hrs and STAM when
      analyzed in the presence of membranes. Consistent with these findings,
      hydrodynamic analysis of endogenous ESCRT-0 indicates that it exists largely as a
      heterotetrameric complex of its two subunits. Based on these data, we present a
      revised model for ESCRT-0 function in cargo recruitment and concentration at the
      endosome.

PMID- 21193407
TI  - Complement receptor Mac-1 is an adaptor for NB1 (CD177)-mediated PR3-ANCA
      neutrophil activation.
AB  - The glycosylphosphatidylinositol (GPI)-anchored neutrophil-specific receptor NB1
      (CD177) presents the autoantigen proteinase 3 (PR3) on the membrane of a
      neutrophil subset. PR3-ANCA-activated neutrophils participate in small-vessel
      vasculitis. Since NB1 lacks an intracellular domain, we characterized components
      of the NB1 signaling complex that are pivotal for neutrophil activation. PR3-ANCA
      resulted in degranulation and superoxide production in the mNB1(pos)/PR3(high)
      neutrophils, but not in the mNB1(neg)/PR3(low) subset, whereas MPO-ANCA and fMLP
      caused similar responses. The NB1 signaling complex that was precipitated from
      plasma membranes contained the transmembrane receptor Mac-1 (CD11b/CD18) as shown
      by MS/MS analysis and immunoblotting. NB1 co-precipitation was less for CD11a and
      not detectable for CD11c. NB1 showed direct protein-protein interactions with
      both CD11b and CD11a by surface plasmon resonance analysis (SPR). However, when
      these integrins were presented as heterodimeric transmembrane proteins on
      transfected cells, only CD11b/CD18 (Mac-1)-transfected cells adhered to
      immobilized NB1 protein. This adhesion was inhibited by mAb against NB1, CD11b,
      and CD18. NB1, PR3, and Mac-1 were located within lipid rafts. In addition,
      confocal microscopy showed the strongest NB1 co-localization with CD11b and CD18
      on the neutrophil. Stimulation with NB1-activating mAb triggered degranulation
      and superoxide production in mNB1(pos)/mPR3(high) neutrophils, and this effect
      was reduced using blocking antibodies to CD11b. CD11b blockade also inhibited PR3
      ANCA-induced neutrophil activation, even when beta2-integrin ligand-dependent
      signals were omitted. We establish the pivotal role of the NB1-Mac-1 receptor
      interaction for PR3-ANCA-mediated neutrophil activation.

PMID- 21193408
TI  - Coactivator function of positive cofactor 4 (PC4) in Sp1-directed luteinizing
      hormone receptor (LHR) gene transcription.
AB  - The LHR has an essential role in sexual development and reproductive function,
      and its transcription is subjected to several modes of regulation. In this study,
      we investigated PC4 coactivator function in the control of LHR transcription.
      Knockdown of PC4 by siRNA inhibited the LHR basal promoter activity and
      trichostatin A (TSA)-induced gene transcriptional activation and expression in
      MCF-7 cells. While overexpression of PC4 alone had no effect on the LHR gene, it
      significantly enhanced Sp1- but not Sp3-mediated LHR transcriptional activity.
      PC4 directly interacts with Sp1 at the LHR promoter, and this interaction is
      negatively regulated by PC4 phosphorylation. The coactivator domain (22-91 aa) of
      PC4 and DNA binding domain of Sp1 are essential for PC4/Sp1 interaction. ChIP
      assay revealed significant occupancy of PC4 at the LHR promoter that increased
      upon TSA treatment. Disruption of PC4 expression significantly reduced TSA
      induced recruitment of TFIIB and RNAP II, at the promoter. PC4 functions are
      beyond TSA-induced phosphatase release, PI3K-mediated Sp1 phosphorylation, and
      HDAC1/2/mSin3A co-repressor release indicating its role as linker coactivator of
      Sp1 and the transcriptional machinery. These findings demonstrated a critical
      aspect of LHR modulation whereby PC4 acts as a coactivator of Sp1 to contribute
      to the human of LHR transcription.

PMID- 21193409
TI  - Bacillus cereus phosphopentomutase is an alkaline phosphatase family member that
      exhibits an altered entry point into the catalytic cycle.
AB  - Bacterial phosphopentomutases (PPMs) are alkaline phosphatase superfamily members
      that interconvert alpha-D-ribose 5-phosphate (ribose 5-phosphate) and alpha-D
      ribose 1-phosphate (ribose 1-phosphate). We investigated the reaction mechanism
      of Bacillus cereus PPM using a combination of structural and biochemical studies.
      Four high resolution crystal structures of B. cereus PPM revealed the active site
      architecture, identified binding sites for the substrate ribose 5-phosphate and
      the activator alpha-D-glucose 1,6-bisphosphate (glucose 1,6-bisphosphate), and
      demonstrated that glucose 1,6-bisphosphate increased phosphorylation of the
      active site residue Thr-85. The phosphorylation of Thr-85 was confirmed by
      Western and mass spectroscopic analyses. Biochemical assays identified Mn(2+)
      dependent enzyme turnover and demonstrated that glucose 1,6-bisphosphate
      treatment increases enzyme activity. These results suggest that protein
      phosphorylation activates the enzyme, which supports an intermolecular
      transferase mechanism. We confirmed intermolecular phosphoryl transfer using an
      isotope relay assay in which PPM reactions containing mixtures of ribose 5
      [(18)O(3)]phosphate and [U-(13)C(5)]ribose 5-phosphate were analyzed by mass
      spectrometry. This intermolecular phosphoryl transfer is seemingly counter to
      what is anticipated from phosphomutases employing a general alkaline phosphatase
      reaction mechanism, which are reported to catalyze intramolecular phosphoryl
      transfer. However, the two mechanisms may be reconciled if substrate encounters
      the enzyme at a different point in the catalytic cycle.

PMID- 21193410
TI  - Mutation of the 5'-untranslated region stem-loop structure inhibits alpha1(I)
      collagen expression in vivo.
AB  - Type I collagen is a heterotrimeric extracellular matrix protein consisting of
      two alpha1(I) chains and one alpha2(I) chain. During liver fibrosis, activated
      hepatic stellate cells (HSCs) are the major source of the type I collagen that
      accumulates in the damaged tissue. Expression of alpha1(I) and alpha2(I) collagen
      mRNA is increased 60-fold compared with quiescent stellate cells and is due
      predominantly to post-transcriptional message regulation. Specifically, a stem
      loop structure in the 5'-untranslated region of alpha1(I) collagen mRNA may
      regulate mRNA expression in activated HSCs through its interaction with stem-loop
      binding proteins. The stem-loop may also be necessary for efficient production
      and folding of the type I collagen heterotrimer. To assess the role of the stem
      loop in type I collagen expression in vivo, we generated a knock-in mouse
      harboring a mutation that abolished the stem-loop structure. Heterozygous and
      homozygous knock-in mice exhibited a normal phenotype. However, steady-state
      levels of alpha1(I) collagen mRNA decreased significantly in homozygous mutant
      MEFs as well as HSCs; intracellular and secreted type I collagen protein levels
      also decreased. Homozygous mutant mice developed less liver fibrosis. These
      results confirm an important role of the 5' stem-loop in regulating type I
      collagen mRNA and protein expression and provide a mouse model for further study
      of collagen-associated diseases.

PMID- 21193411
TI  - The dimer interface of the membrane type 1 matrix metalloproteinase hemopexin
      domain: crystal structure and biological functions.
AB  - Homodimerization is an essential step for membrane type 1 matrix
      metalloproteinase (MT1-MMP) to activate proMMP-2 and to degrade collagen on the
      cell surface. To uncover the molecular basis of the hemopexin (Hpx) domain-driven
      dimerization of MT1-MMP, a crystal structure of the Hpx domain was solved at 1.7
      A resolution. Two interactions were identified as potential biological dimer
      interfaces in the crystal structure, and mutagenesis studies revealed that the
      biological dimer possesses a symmetrical interaction where blades II and III of
      molecule A interact with blades III and II of molecule B. The mutations of amino
      acids involved in the interaction weakened the dimer interaction of Hpx domains
      in solution, and incorporation of these mutations into the full-length enzyme
      significantly inhibited dimer-dependent functions on the cell surface, including
      proMMP-2 activation, collagen degradation, and invasion into the three
      dimensional collagen matrix, whereas dimer-independent functions, including
      gelatin film degradation and two-dimensional cell migration, were not affected.
      These results shed light on the structural basis of MT1-MMP dimerization that is
      crucial to promote cellular invasion.

PMID- 21193413
TI  - Structure-activity analysis of cathepsin K/chondroitin 4-sulfate interactions.
AB  - In the presence of oligomeric chondroitin 4-sulfate (C4-S), cathepsin K (catK)
      forms a specific complex that was shown to be the source of the major
      collagenolytic activity in bone osteoclasts. C4-S forms multiple contacts with
      amino acid residues on the backside of the catK molecule that help to facilitate
      complex formation. As cathepsin L does not exhibit a significant collagenase
      activity in the presence or in the absence of C4-S, we substituted the C4-S
      interacting residues in catK with those of cathepsin L. Variants revealed altered
      collagenolytic activities with the largest inhibitory effect shown by the
      hexavariant M5. None of the variants showed a reduction in their gelatinolytic
      and peptidolytic activities when compared with wild-type catK, indicating no
      structural alteration within their active sites. However, the crystal structure
      of the M5 variant in the presence of oligomeric C4-S revealed a different binding
      of chondroitin 4-sulfate. C4-S is not continuously ordered as it is in the wild
      type catK.C4-S complex. The orientation and the direction of the hexasaccharide
      on the catK surface have changed, so that the hexasaccharide is positioned
      between two symmetry-related molecules. Only one M5 variant molecule of the dimer
      that is present in the asymmetric unit interacts with C4-S. These substitutions
      have changed the mode of catK binding to C4-S and, as a result, have likely
      affected the collagenolytic potential of the variant. The data presented here
      support our hypothesis that distinct catK/C4-S interactions are necessary for the
      collagenolytic activity of the enzyme.

PMID- 21193412
TI  - Pregnancy-specific glycoprotein 1 induces endothelial tubulogenesis through
      interaction with cell surface proteoglycans.
AB  - Pregnancy-specific beta1 glycoproteins (PSGs) are the most abundant fetal
      proteins in the maternal bloodstream in late pregnancy. They are secreted by the
      syncytiotrophoblast and are detected around day 14 postfertilization. There are
      11 human PSG genes, which encode a family of proteins exhibiting significant
      conservation at the amino acid level. We and others have proposed that PSGs have
      an immune modulatory function. In addition, we recently postulated that they are
      proangiogenic due to their ability to induce the secretion of VEGF-A and the
      formation of tubes by endothelial cells. The cellular receptor(s) for human PSGs
      remain unknown. Therefore, we conducted these studies to identify the receptor
      for PSG1, the highest expressed member of the family. We show that removal of
      cell surface glycosaminoglycans (GAGs) by enzymatic or chemical treatment of
      cells or competition with heparin completely inhibited binding of PSG1. In
      addition, PSG1 did not bind to cells lacking heparan or chondroitin sulfate on
      their surface, and binding was restored upon transfection with all four syndecans
      and glypican-1. Importantly, the presence of GAGs on the surface of endothelial
      cells was required for the ability of PSG1 to induce tube formation. This finding
      indicates that the PSG1-GAG interaction mediates at least some of the PSG1
      proposed functions.

PMID- 21193414
TI  - Lack of collagen XVIII long isoforms affects kidney podocytes, whereas the short
      form is needed in the proximal tubular basement membrane.
AB  - Collagen XVIII is characterized by three variant N termini, an interrupted
      collagenous domain, and a C-terminal antiangiogenic domain known as endostatin.
      We studied here the roles of this collagen type and its variant isoforms in the
      mouse kidney. Collagen XVIII appeared to be in a polarized orientation in the
      tubular basement membranes (BMs), the endostatin domain embedded in the BM, and
      the N terminus residing at the BM-fibrillar matrix interface. In the case of the
      glomerular BM (GBM), collagen XVIII was expressed in different isoforms depending
      on the side of the GBM. The orientation appeared polarized here, too, both the
      endothelial promoter 1-derived short variant of collagen XVIII and the epithelial
      promoter 2-derived longer variants having their C-terminal endostatin domains
      embedded in the BM and the N termini at the respective BM-cell interfaces. In
      addition to loosening of the proximal tubular BM structure, the Col18a1(-/-) mice
      showed effacement of the glomerular podocyte foot processes, and microindentation
      studies showed changes in the mechanical properties of the glomeruli, the
      Col18a1(-/-) glomeruli being ~30% softer than the wild-type. Analysis of promoter
      specific knockouts (Col18a1(P1/P1) and Col18a1(P2/P2)) indicated that tubular BM
      loosening is due to a lack of the shortest isoform, whereas the glomerular
      podocyte effacement was due to a lack of the longer isoforms. We suggest that
      lack of collagen XVIII may also have disparate effects on kidney function in man,
      but considering the mild physiological findings in the mutant mice, such effects
      may manifest themselves only late in life or require other compounding molecular
      changes.

PMID- 21193416
TI  - Isolated bone marrow mastocytosis: an underestimated subvariant of indolent
      systemic mastocytosis.

PMID- 21193415
TI  - Structure-function analysis of tetraspanin CD151 reveals distinct requirements
      for tumor cell behaviors mediated by alpha3beta1 versus alpha6beta4 integrin.
AB  - The basement membrane protein laminin-332 (laminin-5) mediates both stable cell
      adhesion and rapid cell migration and thus has the potential to either restrain
      or promote tumor cell metastasis. The major cellular receptors for laminin-332
      are integrin alpha3beta1, which mediates rapid tumor cell migration, and integrin
      alpha6beta4, which often mediates stable cell attachment. Tetraspanin protein
      CD151 interacts directly with both alpha3beta1 and alpha6beta4 integrins and with
      other tetraspanins, thereby promoting alpha3beta1 and alpha6beta4 association
      with tetraspanin-enriched microdomains on the cell surface. To explore the
      possibility of selectively modulating tumor cell responses to laminin-332, we re
      expressed a series of CD151 mutants in epidermoid carcinoma cells with near
      total, RNAi-mediated silencing of endogenous CD151. The interactions of CD151
      with its integrin partners or its interactions with other tetraspanins were
      selectively disrupted by specific mutations in the CD151 large extracellular loop
      (EC2 domain) or in intracellular CD151 palmitoylation sites, respectively. CD151
      integrin association and CD151-tetraspanin association were both important for
      alpha3beta1 integrin-dependent initial adhesion and rapid migration on laminin
      332. Remarkably, however, only CD151-integrin association was required for
      stable, alpha6beta4 integrin-dependent cell attachment on laminin-332. In
      addition, we found that a QRD amino acid motif in the CD151 EC2 domain, which had
      been thought to be crucial for CD151-integrin interaction, is not essential for
      CD151-integrin association or for the ability of CD151 to promote several
      different integrin functions. These new data suggest potential strategies for
      selectively modulating migratory cell responses to laminin-332, while leaving
      stable cell attachment on laminin-332 intact.

PMID- 21193417
TI  - White blood cell count at diagnosis and immunoglobulin variable region gene
      mutations are independent predictors of treatment-free survival in young patients
      with stage A chronic lymphocytic leukemia.
AB  - A comprehensive panel of clinical-biological parameters was prospectively
      evaluated at presentation in 112 patients with chronic lymphocytic leukemia (<65
      years), to predict the risk of progression in early stage disease. Eighty-one
      percent were in Binet stage A, 19% in stages B/C. Treatment-free survival was
      evaluated as the time from diagnosis to first treatment, death or last follow up.
      In univariate analysis, advanced stage, hemoglobin, platelets, white blood cell,
      leukemic lymphocyte count, raised beta 2-microglobulin and LDH, unmutated
      immunoglobulin variable region genes, CD38, del(17p), del(11q) and +12, were
      significantly associated with a short treatment-free survival; the T/leukemic
      lymphocyte ratio was associated with a better outcome. Multivariate analysis of
      treatment-free survival in stage A patients selected a high white blood cell
      count and unmutated immunoglobulin variable region genes as unfavorable
      prognostic factors and a high T/leukemic lymphocyte ratio as a favorable one. At
      diagnosis, these parameters independently predict the risk of progression in
      stage A chronic lymphocytic leukemia patients.

PMID- 21193418
TI  - Establishment of a xenograft model of human myelodysplastic syndromes.
AB  - BACKGROUND: To understand how myelodysplastic syndrome cells evolve from normal
      stem cells and gain competitive advantages over normal hematopoiesis, we
      established a murine xenograft model harboring bone marrow cells from patients
      with myelodysplastic syndromes or acute myeloid leukemia with myelodysplasia
      related changes. DESIGN AND METHODS: Bone marrow CD34(+) cells obtained from
      patients were injected, with or without human mesenchymal stem cells, into the
      bone marrow of non-obese diabetic/severe combined immunodeficient/IL2Rgamma(null)
      hosts. Engraftment and differentiation of cells derived from the patients were
      investigated by flow cytometry and immunohistochemical analysis. RESULTS: Co
      injection of patients' cells and human mesenchymal stem cells led to successful
      engraftment of patient-derived cells that maintained the immunophenotypes and
      genomic abnormalities of the original patients. Myelodysplastic syndrome
      originated clones differentiated into mature neutrophils, megakaryocytes, and
      erythroblasts. Two of the samples derived from patients with acute myeloid
      leukemia with myelodysplasia-related changes were able to sustain neoplastic
      growth into the next generation while these cells had limited differentiation
      ability in the murine host. The hematopoiesis of mice engrafted with patients'
      cells was significantly suppressed even when human cells accounted for less than
      1% of total marrow mononuclear cells. Histological studies revealed invasion of
      the endosteal surface by patient-derived CD34(+) cells and disruption of
      extracellular matrix architecture, which probably caused inhibition of murine
      hematopoiesis. CONCLUSIONS: We established murine models of human myelodysplastic
      syndromes using cells obtained from patients: the presence of neoplastic cells
      was associated with the suppression of normal host hematopoiesis. The efficiency
      of engraftment was related to the presence of an abnormality in chromosome 7.

PMID- 21193419
TI  - Philadelphia-positive acute lymphoblastic leukemia patients already harbor BCR
      ABL kinase domain mutations at low levels at the time of diagnosis.
AB  - BACKGROUND: In patients with Philadelphia-positive acute lymphoblastic leukemia,
      resistance to treatment with tyrosine kinase inhibitors is frequent and most
      often associated with the development of point mutations in the BCR-ABL kinase
      domain. We aimed to assess: (i) in how many patients BCR-ABL kinase domain
      mutations are already detectable at relatively low levels at the time of
      diagnosis, and (ii) whether mutation detection correlates with subsequent
      response to therapy. DESIGN AND METHODS: We retrospectively analyzed samples
      collected at diagnosis from 15 patients with Philadelphia-positive acute
      lymphoblastic leukemia who subsequently received tyrosine kinase inhibitor
      therapy (dasatinib) by cloning the BCR-ABL kinase domain in a bacterial vector
      and sequencing 200 independent clones per sample. RESULTS: Mutations at
      relatively low levels (2-4 clones out of 200) could be detected in all patients-
      eight who relapsed and seven who achieved persistent remission. Each patient had
      evidence of two to eight different mutations, the majority of which have never
      been reported in association with resistance to tyrosine kinase inhibitors. In
      two patients out of six who relapsed because of a mutation, the mutation (a
      T315I) was already detectable in a few clones at the time of diagnosis. On the
      other hand, a patient who was found to harbor an F317L mutation is in persistent
      remission on dasatinib. CONCLUSIONS: Our results suggest that the BCR-ABL kinase
      domain is prone to randomly accumulate point mutations in Philadelphia-positive
      acute lymphoblastic leukemia, although the presence of these mutations in a
      relatively small leukemic subclone does not always preclude a primary response to
      tyrosine kinase inhibitors.

PMID- 21193420
TI  - MOHITO, a novel mouse cytokine-dependent T-cell line, enables studies of
      oncogenic signaling in the T-cell context.
AB  - The mouse pro-B cell line Ba/F3 has gained major interest as a model system to
      investigate oncogenic tyrosine kinases and to determine the efficacy of kinase
      inhibitors. While Ba/F3 cells are suitable to study oncogenic kinases derived
      from various cell types, the signaling networks in Ba/F3 cells are B-cell
      specific. We have established a mouse CD4+CD8+ double positive T-cell line (named
      MOHITO, for MOuse Hematopoietic Interleukin-dependent cell line of T-cell Origin)
      that has many features of human T-cell acute lymphoblastic leukemia (Notch1 and
      Jak1 mutation, TCR rearrangement) and is dependent on interleukin-7. The MOHITO
      cell line can be transformed to cytokine independent proliferation by BCR-ABL1 or
      mutant JAK1. This mouse T-cell line is a novel model system to investigate
      protein signaling and inhibition in a T-cell specific context and is a valuable
      tool to study and verify oncogenic capacity of mutations in the kinome and
      phosphatome in T-cell malignancies.

PMID- 21193421
TI  - Presenting features and treatment outcome of acute promyelocytic leukemia arising
      after multiple sclerosis.
AB  - We report the clinical features and treatment outcome of 33 patients with
      multiple sclerosis who developed acute promyelocytic leukemia. Thirty patients
      were previously exposed to mitoxantrone. The median latency period between
      treatment initiation and acute promyelocytic leukemia diagnosis was 32 months.
      The PML-RARA bcr1 iso-form was identified in 87% of cases. Twenty-nine (90%)
      patients achieved hematologic remission after all-trans retinoic acid and
      chemotherapy (n = 31) or arsenic trioxide and all-trans retinoic acid.
      Consolidation included modified chemotherapy or arsenic trioxide. At a median
      follow up of 26 months, 23 patients are in complete remission, 4 relapsed and one
      developed secondary leukemia. The 5-year cumulative incidence of relapse and
      overall survival were 23% and 68%, respectively. Although treatment heterogeneity
      and suboptimal post-remission therapy must be taken into account, overall results
      and development of secondary leukemia in one patient suggest that effective and
      less toxic agents like arsenic trioxide warrants further investigation in this
      context.

PMID- 21193422
TI  - Vitamin K1 supplementation to improve the stability of anticoagulation therapy
      with vitamin K antagonists: a dose-finding study.
AB  - BACKGROUND: Poor anticoagulant stability in patients using vitamin K antagonists
      is a risk factor for both bleeding and thrombosis. In previous studies
      supplementation with low dose vitamin K(1) was shown to improve the stability of
      anticoagulant control. We set up a study to confirm earlier reports and to
      determine the optimal daily dose of vitamin K(1) in preparation of a large study
      with clinical endpoints. DESIGN AND METHODS: Four hundred patients from two
      anticoagulation clinics starting with vitamin K antagonists, independently of a
      possible history of instable anticoagulation, were randomized to receive either
      placebo or 100, 150 or 200 MUg of vitamin K(1) together with their treatment with
      vitamin K antagonists. The treatment was administered for 6 to 12 months.
      Anticoagulation stability, expressed as the percentage of time that the
      International Normalized Ratio was within the therapeutic range, was compared
      between the groups. RESULTS: After adjustment for age, sex, vitamin K antagonist
      used, anticoagulation clinic and interacting drugs as confounding factors the
      difference in percentage of time with the International Normalized Ratio within
      the therapeutic range between the placebo group and the vitamin K(1) groups was
      2.1% (95% CI: -3.2% - 7.4%) for the group taking 100 MUg, 2.7% (95% CI: -2.3% 
      7.6%) for the group taking 150 MUg and 0.9% (95% CI: -4.5% - 6.3%) for the group
      taking 200 MUg vitamin K(1) group, in favor of the vitamin K(1) groups. The
      patients from both the 100 MUg group and the 150 MUg group had a 2-fold higher
      chance of reaching at least 85% of time with the International Normalized Ratio
      within the therapeutic range. There were no differences in thromboembolic or
      hemorrhagic complications between the groups. CONCLUSIONS: In patients starting
      vitamin K antagonists, supplementation with low dose vitamin K(1) resulted in an
      improvement of time that anticoagulation was within the therapeutic range.
      Differences between doses were, however, small and the improvement is unlikely to
      be of clinical relevance. For future studies we recommend selecting only patients
      with instable anticoagulant control. (This study was registered at www.isrctn.org
      as ISRCTN37109430).

PMID- 21193423
TI  - ETV6-ABL1-positive "chronic myeloid leukemia": clinical and molecular response to
      tyrosine kinase inhibition.

PMID- 21193424
TI  - Multidrug resistant Pseudomonas aeruginosa bloodstream infection in adult
      patients with hematologic malignancies.

PMID- 21193426
TI  - Vascular risk assessment in patients with sickle cell disease.

PMID- 21193427
TI  - In search of the optimal iron chelation therapy for patients with thalassemia
      major.

PMID- 21193428
TI  - Prognostic relevance of anemia and transfusion dependency in myelodysplastic
      syndromes and primary myelofibrosis.

PMID- 21193429
TI  - Determinants of platelet count in humans.

PMID- 21193430
TI  - In mixed hematopoietic chimerism, the donor red cells win.

PMID- 21193431
TI  - Complete estrogen receptor blocker ICI182,780 promotes the proliferation of
      vascular smooth muscle cells.
AB  - ICI182,780 is used in adjuvant therapies of breast cancer. As a complete estrogen
      receptor (ER) blocker, ICI182,780 may antagonize the effects of estrogen on the
      cardiovascular system. Estrogen inhibits the proliferation of vascular smooth
      muscle cells (VSMCs), which is one of the mechanisms that estrogen can exert
      cardioprotective effects. In the present study, to assess the effects of
      ICI182,780 on the proliferation of VSMCs, we cultured VSMCs isolated from rat
      aorta with or without the ER antagonist ICI182,780. The results of 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, bromodeoxyuridine
      incorporation assay, viable cell count, immunochemical staining for proliferating
      cell nuclear antigen (PCNA), and S-phase ratio determined by flow cytometry
      revealed a remarkable proliferation of VSMCs after ICI182,780 treatment.
      ICI182,780 significantly enhanced cell growth in a dose-dependent manner (10(-8)
      10(-5) M). Furthermore, the number of PCNA-positive cells and the S-phase
      progression of VSMCs increased after treatment with ICI182,780. Reverse
      transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis showed
      that the mRNA and protein level of cyclin D1 in VSMCs increased under the
      treatment of ICI182,780. These data suggested that ICI182,780 can promote the
      growth of VSMCs, which might produce some adverse effects on the cardiovascular
      system.

PMID- 21193432
TI  - Mental health and unintentional injurers: results from the national co-morbidity
      survey replication.
AB  - OBJECTIVE: To examine whether unintentionally injuring others is associated with
      subsequent mental illness, and whether mental illness is a risk factor for
      unintentionally injuring others. METHODS: Onset of first psychiatric diagnoses
      was compared with onset of first unintentional injuring. Multivariate logistic
      regression estimated the association between unintentional injuring and lifetime
      prevalence of mental illness, specifically of Diagnostic and Statistical Manual
      of Mental Disorders IV disorders associated with trauma exposure among
      respondents of part II of the National Co-morbidity Survey Replication a
      household survey of 5692 US adults. Analyses controlled for age, sex, race and
      having been injured in a serious accident. RESULTS: Of 5692 respondents, 110
      reported unintentionally causing death or injury to another person.
      Unintentionally injuring others was a risk factor for subsequent mental health
      problems. Multivariate regression results showed an increased risk of subsequent
      depression (OR 3.1, CI 1.7 to 5.7), anxiety (OR 3.3, CI 1.6 to 6.6),
      posttraumatic stress disorder (PTSD) (OR 6.6, CI 3.1 to 14.0), alcohol use (OR
      3.8, CI 1.9 to 7.3) and drug use (OR 8.0, CI 4.1 to 15.3). Conversely, mental
      health problems were a risk factor for unintentionally injuring another person.
      Multivariate regression results showed an increased risk of unintentional
      injuring among those with a prior diagnosis of depression, PTSD, alcohol use, and
      drug use. CONCLUSIONS: After injuring, unintentional injurers are likely to
      experience depression, anxiety, PTSD and drug or alcohol abuse/dependence
      compared with non-injurers. Those diagnosed with depression, anxiety, PTSD,
      alcohol or drug or alcohol abuse/dependence are more likely to cause serious
      injuries to others.

PMID- 21193433
TI  - Excimer laser lead extraction by femoral approach.

PMID- 21193434
TI  - Hepatocyte growth factor mobilizes non-bone marrow-derived circulating
      mesoangioblasts.
AB  - AIMS: The identification of factors that mobilize subsets of endogenous
      progenitor cells may provide new therapeutic tools to enhance the repair of
      ischaemic tissue. We previously identified circulating mesenchymal cells that co
      express endothelial markers (so-called circulating mesoangioblasts, cMABs) in
      children undergoing heart surgery with cardiopulmonary bypass (CPB). However, the
      mechanisms by which these cells are mobilized and their origin is unclear.
      METHODS AND RESULTS: Circulating CD73(+)CD45(-)KDR(+) cMABs were analysed in
      adults undergoing heart surgery with (n = 21) or without CPB (n = 8). During
      surgery with CPB, cMABs are mobilized with a maximal response at the end of the
      operation. In contrast, off-pump heart surgery does not stimulate cMAB
      mobilization, indicating that the stress mediated by CPB induces the mobilization
      of cMAB. Circulating mesoangioblasts were enriched in blood obtained from the
      coronary sinus. Histologically, CD73(+) cells were detected around vessels in the
      heart, indicating that the heart is one of the niches of cMABs. Consistently,
      studies in gender mismatched bone marrow transplanted patients demonstrated that
      cMABs did not originate from the bone marrow. Cytokine profiling of serum samples
      revealed that hepatocyte growth factor (HGF) was profoundly increased at the time
      point of maximal mobilization of cMABs. Hepatocyte growth factor stimulated the
      migration of cMABs. Importantly, injection of recombinant HGF increased cMABs in
      rats. CONCLUSIONS: Hepatocyte growth factor induces mobilization of non
      haematopoietic progenitor cells with a cardiac repair capacity. This newly
      identified function together with the known pleiotrophic effects of HGF makes HGF
      an attractive therapeutic option for the treatment of ischaemic heart disease.

PMID- 21193435
TI  - Intraleaflet haemorrhage is associated with rapid progression of degenerative
      aortic valve stenosis.
AB  - AIMS: The haemorrhage in the plaque (intraplaque haemorrhage) plays a critical
      role in the progression of atherosclerosis. The purpose of this study is to
      clarify whether the haemorrhage in the aortic valve leaflet (intraleaflet
      haemorrhage) accelerates the progression of aortic valve stenosis (AS). METHODS
      AND RESULTS: We examined specimens of aortic valve leaflets obtained from 36
      patients who had undergone aortic valve replacement for degenerative AS and in
      whom echocardiographic data were available just before the operation and at least
      180 days before the last study. The stenotic valves were examined by
      immunohistochemistry to detect intraleaflet haemorrhage with antibody against
      glycophorin A, an erythrocyte-specific protein. The progression of AS was
      assessed by annualized change in the aortic valve area (DeltaAVA: cm(2)/year).
      The patients were divided into two groups, namely the rapid progression group
      (DeltaAVA >= 0.1 cm(2)/year) and the slow progression group (DeltaAVA < 0.1
      cm(2)/year), according to the reported average progression rate of AS.
      Intraleaflet haemorrhage was observed in 78 % of the specimens. Intraleaflet
      haemorrhage was associated with neovascularization and macrophage infiltration.
      The areas of intraleaflet haemorrhage and macrophage infiltration were greater in
      the rapid progression group than in the slow progression group. Multivariate
      analysis has shown that the area of intraleaflet haemorrhage was the sole
      independent factor that positively correlated with DeltaAVA. CONCLUSIONS:
      Intraleaflet haemorrhage was frequently observed in the valve leaflets of
      degenerative AS and associated with a rapid progression of AS.

PMID- 21193436
TI  - Left coronary sinus to pulmonary artery fistula, complicated by pulmonary valve
      endocarditis.

PMID- 21193437
TI  - Isolated left ventricular non-compaction in adults: clinical and
      echocardiographic features in 105 patients. Results from a French registry.
AB  - AIMS: The clinical features, prognosis, and even definition of left ventricular
      non-compaction (LVNC) are still the subject of much debate. The aim of this
      registry was to describe the clinical, echocardiographic, and prognostic features
      of LVNC in France. The main endpoint was to assess clinical and echocardiographic
      predictors of adverse outcome, defined as death or heart transplantation. METHODS
      AND RESULTS: Between 2004 and 2006, 154 suspected cases of LNVC were identified
      from a nationwide survey in France. The diagnosis of LVNC was confirmed in 105
      cases by echocardiographic evaluation in a core laboratory. Clinical and
      echocardiographic data for the 105 cases of LVNC are presented. Left ventricular
      non-compaction was first detected from heart failure symptoms in 45 patients,
      rhythm disorders in 12, and familial screening in 8. Left ventricular ejection
      fraction (LVEF) was < 30% in 46% of patients, but >= 50% in 16%. The latter had
      less symptoms of severe heart failure (11 vs. 54%, P = 0.001), but similar
      extension of the NC zone. During 2.33 +/- 1.47 years of follow-up, several
      complications occurred, including severe heart failure in 33 patients,
      transplantation in 9, ventricular arrhythmia in 7, embolic events in 9, and death
      in 12. Factors associated with death or heart transplantation were NYHA 3 or 4
      (HR = 6.69; P = 0.0007), high LV filling pressures (HR = 7.59; P = 0.001), LVEF
      (HR = 0.93; P = 0.006), and hospitalization for heart failure (HR = 13.55; P <
      0.0001). CONCLUSION: In this large reported series of LVNC, we observed that: (i)
      Left ventricular non-compaction was detected by familial screening in
      asymptomatic patients in 8% of cases. (ii) Left ventricular non-compaction was
      frequently over-diagnosed by echocardiography. (iii) Patients identified as LVNC
      presented with a high risk of severe complications, transplantation or death and
      needed close follow-up.

PMID- 21193438
TI  - Time-trends in treatment and cardiovascular events in patients with heart
      failure: a pharmacosurveillance study.
AB  - AIMS: We assessed, in patients with a first hospitalization for heart failure
      (HF), the temporal relationship of the incidence of cardiovascular events, all
      cause mortality, and cardiovascular drug treatment. METHODS AND RESULTS: Data
      were obtained from the PHARMO Record Linkage System, a population-based registry
      of pharmacy records linked with hospital discharge records in The Netherlands.
      Patients were selected based on a first hospital discharge diagnosis of
      documented HF. Two time-periods were compared: 1998-2002 and 2003-07. In each
      time-period, we analysed all prescribed cardiovascular medications, all-cause
      mortality, and cardiovascular events (rehospitalization for HF and ischaemic
      events) within the first year after hospitalization, and the occurrence of
      ischaemic events separately (myocardial infarction and ischaemic stroke). Cox
      regression analysis was performed to calculate hazard ratios (HR) with 95%
      confidence intervals (CI). We identified 8276 patients in 1998-2002 and 9548
      patients from 2003-07. There was an increase in almost all cardiovascular
      medication prescriptions in the second period: in particular, beta-blocker
      prescriptions rose from 36% in 1998-2002 to 55% in 2003-07. In the first year
      after hospitalization, there was no difference in all-cause mortality or any
      cardiovascular event (HR 1.00, 95%CI: 0.95-1.05), as a composite endpoint or when
      analysed separately. The incidence of ischaemic events decreased from 2.7 to 1.9%
      in the first and second time-period, respectively (HR 0.74, 95%CI: 0.61-0.90).
      CONCLUSION: Prescription of cardiovascular medications in patients with a first
      hospitalization for HF has increased in recent years, particularly for beta
      blockers, and the incidence of ischaemic events may have decreased. There was no
      decrease in all-cause mortality or cardiovascular events.

PMID- 21193439
TI  - Economic impact of remote patient monitoring: an integrated economic model
      derived from a meta-analysis of randomized controlled trials in heart failure.
AB  - AIMS: To assess the cost-effectiveness and the cost utility of remote patient
      monitoring (RPM) when compared with the usual care approach based upon
      differences in the number of hospitalizations, estimated from a meta-analysis of
      randomized clinical trials (RCTs). METHODS AND RESULTS: We reviewed the
      literature published between January 2000 and September 2009 on multidisciplinary
      heart failure (HF) management, either by usual care or RPM to retrieve the number
      of hospitalizations and length of stay (LOS) for HF and for any cause. We
      performed a meta-analysis of 21 RCTs (5715 patients). Remote patient monitoring
      was associated with a significantly lower number of hospitalizations for HF
      [incidence rate ratio (IRR): 0.77, 95% CI 0.65-0.91, P < 0.001] and for any cause
      (IRR: 0.87, 95% CI: 0.79-0.96, P = 0.003), while LOS was not different. Direct
      costs for hospitalization for HF were approximated by diagnosis-related group
      (DRG) tariffs in Europe and North America and were used to populate an economic
      model. The difference in costs between RPM and usual care ranged from ?300 to
      ?1000, favouring RPM. These cost savings combined with a quality-adjusted life
      years (QALYs) gain of 0.06 suggest that RPM is a 'dominant' technology over
      existing standard care. In a budget impact analysis, the adoption of an RPM
      strategy entailed a progressive and linear increase in costs saved. CONCLUSIONS:
      The novel cost-effectiveness data coupled with the demonstrated clinical efficacy
      of RPM should encourage its acceptance amongst clinicians and its consideration
      by third-party payers. At the same time, the scientific community should
      acknowledge the lack of prospectively and uniformly collected economic data and
      should request that future studies incorporate economic analyses.

PMID- 21193440
TI  - Iron in the inflammed gut: another pro-inflammatory hit?

PMID- 21193441
TI  - Immunogenicity of anti-TNF antibodies. Has the veil been lifted?

PMID- 21193442
TI  - A patient with biliary colic and intestinal obstruction.

PMID- 21193443
TI  - Levofloxacin in first-line eradication regimens for Helicobacter pylori: better
      test antibiotic susceptibility before treating.

PMID- 21193444
TI  - Immediate effect on fertility of a gluten-free diet in women with untreated
      coeliac disease.

PMID- 21193445
TI  - Antibodies to GP2, the major zymogen granule membrane glycoprotein, in
      inflammatory bowel diseases.

PMID- 21193446
TI  - Sequential therapy for Helicobacter pylori eradication: is levofloxacin better?

PMID- 21193447
TI  - Limited effect of summer warming on the sensitivity of colorectal cancer
      screening.

PMID- 21193449
TI  - Enteric Salmonella or Campylobacter infections and the risk of inflammatory bowel
      disease.
AB  - OBJECTIVE: Enteric pathogens have been implicated in the aetiology of
      inflammatory bowel disease (IBD), but increased rates of stool testing of
      patients with unclear gastrointestinal symptoms might cause detection bias.
      Hence, the objective of this study was to analyse incidence rates of Crohn's
      disease and ulcerative colitis among patients with Salmonella- or Campylobacter
      positive and negative stool tests and to study the incidence of positive and
      negative stool tests among patients already diagnosed with IBD. METHODS: The
      Danish population was followed for 94.3 million person-years during 1992-2008
      using national registers to identify persons with positive and negative stool
      tests and patients with IBD. Using Poisson regression, incidence rate ratios
      (IRRs) for IBD after positive or negative stool tests and, conversely, IRRs for
      positive and negative stool tests following IBD, were calculated. RESULTS: IRRs
      for IBD were significantly high in the first year after Salmonella- or
      Campylobacter-positive stool tests (IRRs 5.4-9.8), and they remained moderately
      increased 1-10 years later (IRRs 1.6-2.2), and less so >10 years later (IRRs 0.8
      1.8). However, IRRs for IBD <1 year after a negative stool test were several-fold
      higher (IRRs 53.2-57.5), and a decreasing incidence pattern over time was
      parallel to that following positive test results. Among patients with IBD, IRRs
      for subsequent positive and-most notably-negative stool test results were also
      significantly high. CONCLUSION: Similarities in temporal risk patterns for IBD
      following positive or negative stool tests indicate that the increased occurrence
      of Salmonella- or Campylobacter-positive results around the time of first IBD
      hospitalisation results from detection bias.

PMID- 21193450
TI  - Analysis of deaths occurring within the Nottingham trial of faecal occult blood
      screening for colorectal cancer.

PMID- 21193451
TI  - Metachronous colorectal cancer risk for mismatch repair gene mutation carriers:
      the advantage of more extensive colon surgery.
AB  - BACKGROUND: Surgical management of colon cancer for patients with Lynch syndrome
      who carry a mismatch repair (MMR) gene mutation is controversial. The decision to
      remove more or less of the colon involves the consideration of a relatively high
      risk of metachronous colorectal cancer (CRC) with the impact of more extensive
      surgery. OBJECTIVE: To estimate and compare the risks of metachronous CRC for
      patients with Lynch syndrome undergoing either segmental or extensive (subtotal
      or total) resection for first colon cancer. DESIGN: Risk of metachronous CRC was
      estimated for 382 MMR gene mutation carriers (172 MLH1, 167 MSH2, 23 MSH6 and 20
      PMS2) from the Colon Cancer Family Registry, who had surgery for their first
      colon cancer, using retrospective cohort analysis. Age-dependent cumulative risks
      of metachronous CRC were calculated using the Kaplan-Meier method. Risk factors
      for metachronous CRC were assessed by a Cox proportional hazards regression.
      RESULTS: None of 50 subjects who had extensive colectomy was diagnosed with
      metachronous CRC (incidence rate 0.0; 95% CI 0.0 to 7.2 per 1000 person-years).
      Of 332 subjects who had segmental resections, 74 (22%) were diagnosed with
      metachronous CRC (incidence rate 23.6; 95% CI 18.8 to 29.7 per 1000 person
      years). For those who had segmental resections, incidence was statistically
      higher than for those who had extensive surgery (P <0.001). Cumulative risk of
      metachronous CRC was 16% (95% CI 10% to 25%) at 10 years, 41% (95% CI 30% to 52%)
      at 20 years and 62% (95% CI 50% to 77%) at 30 years after segmental colectomy.
      Risk of metachronous CRC reduced by 31% (95% CI 12% to 46%; p=0.002) for every 10
      cm of bowel removed. CONCLUSIONS: Patients with Lynch syndrome with first colon
      cancer treated with more extensive colonic resection have a lower risk of
      metachronous CRC than those receiving less extensive surgery. This finding will
      better inform decision-making about the extent of primary surgical resection.

PMID- 21193452
TI  - Effects of anti-reflux surgery on weakly acidic reflux and belching.
AB  - BACKGROUND: Laparoscopic Nissen fundoplication (LNF) is the most frequently
      performed operation for gastro-oesophageal reflux disease (GORD). However, 12% of
      the patients have persistent reflux symptoms and 19% develop gas-related symptoms
      after LNF. Weakly acidic reflux and inability to belch have been alleged to cause
      these symptoms, respectively. The effect of LNF on weakly acidic reflux and
      (supra) gastric belching was evaluated. METHODS: In 31 patients upper
      gastrointestinal endoscopy, stationary oesophageal manometry and 24-h impedance
      pH monitoring off acid secretion inhibiting drugs was performed before and 6
      months after primary LNF for GORD that was refractory to proton pump inhibitors.
      Patients filled out validated questionnaires on GERD-HRQoL before and 3, 6 and 12
      months after surgery. RESULTS: LNF reduced reflux symptoms (18.6->1.6; p =
      0.015). The procedure drastically reduced the incidence (number per 24 h) of acid
      (76.0->1.6; p < 0.001) and weakly acidic (13.6->5.7; p = 0.001) as well as liquid
      (53.4->5.4; p<0.001) and mixed reflux episodes (36.3->1.9; p < 0.001). In
      contrast, gas reflux was reduced to lesser extent (35.6->25.7; p = 0.022).
      Proximal, mid-oesophageal and distal reflux were reduced to a similar extent.
      Persistent GORD symptoms were neither preceded by acid nor by weakly acidic
      reflux. The number of air swallows did not change, but the number of gastric
      belches (GBs) was greatly reduced (68.5->23.9; p < 0.001). Twenty-three patients
      had supragastric belches (SGBs), both before and after surgery, whereas eight
      patients had no SGBs at all. The majority of SGBs were not reflux associated and
      the frequency was greatly increased after LNF (20.8->46.0; p = 0.036). Reflux
      associated SGBs were abolished after surgery (14.0->0.4; p < 0.001). CONCLUSIONS:
      LNF similarly controls acid and weakly acidic reflux, but gas reflux is reduced
      to lesser extent. Persistent reflux symptoms are neither caused by acid nor by
      weakly acidic reflux. LNF alters the belching pattern by reducing GBs (air
      venting from stomach) and increasing SGBs (no air venting from stomach). This
      explains the increase in belching experienced by some patients after LNF, despite
      the reduction in gastric belching. It can be hypothesised that the reduction in
      GBs after LNF incites patients to increase SGBs in a futile attempt to vent air
      from the stomach.

PMID- 21193453
TI  - Prognostic relevance of morphological types of intraductal papillary mucinous
      neoplasms of the pancreas.
AB  - OBJECTIVE: The clinicopathological significance of four morphological types of
      intraductal papillary mucinous neoplasms of the pancreas (IPMNs; gastric,
      intestinal, pancreatobiliary and oncocytic) was assessed. DESIGN: Retrospective
      multicentre analysis of 283 surgically resected IPMNs. RESULTS: Of the 283 IPMNs,
      139 were of the gastric type, 101 were intestinal, 19 were pancreatobiliary and
      24 were oncocytic. These types were significantly associated with
      clinicopathological factors including sex (p = 0.0032), age (p = 0.00924),
      ectatic duct size (p = 0.0245), detection of mural nodules (p = 4.09 * 10-6),
      histological grade (p < 2.20 * 10-16), macroscopic types with differential
      involvement of the pancreatic duct system (p = 3.91 * 10-5), invasive phenotypes
      (p = 3.34 * 10-12), stage (p < 2.20 * 10-16) and recurrence (p = 0.00574). Kaplan
      Meier analysis showed significant differences in patient survival by
      morphological type (p = 5.24 * 10-6). Survival rates at 5 and 10 years,
      respectively, were 0.937 (95% CI 0.892 to 0.984) for patients with gastric-type
      IPMNs; 0.886 (95% CI 0.813 to 0.965) and 0.685 (95% CI 0.553 to 0.849) for those
      with intestinal-type IPMNs; 0.839 (95% CI 0.684 to 1.000) and 0.734 (95% CI 0.526
      to 1.000) for those with oncocytic-type IPMNs; and 0.520 (95% CI 0.298 to 0.909)
      and undetermined for those with pancreatobiliary-type IPMNs. Analysis by the Cox
      proportional hazards model comparing prognostic risks determined by stage and the
      morphological and macroscopic types indicated that staging was the most
      significant predictor of survival (p = 3.68*10-8) followed by the morphological
      type (p = 0.0435). Furthermore, the morphological type remained a significant
      predictor in a subcohort of invasive cases (p = 0.0089). CONCLUSION: In this
      multicentre retrospective analysis, the morphological type of IPMN appears to be
      an independent predictor of patient prognosis.

PMID- 21193454
TI  - Roles of Kruppel-like factor 4 in oesophageal epithelial cells in Barrett's
      epithelium development.
AB  - OBJECTIVES: The mechanism of transformation to intestinal metaplasia in Barrett's
      oesophagus has not been clarified. We previously reported that bile acids
      activate the Cdx2 promoter via nuclear factor kappa B (NF-kappaB) and stimulate
      production of Cdx2 protein in oesophageal keratinocytes, resulting in production
      of intestinal-type mucin. Kruppel-like factor 4 (KLF4) is an important
      transcription factor in the development of intestinal mucosa and has similar
      functions as Cdx2. In the present study, we investigated the direct effects of
      bile acids on KLF4 expression as well as the precise mechanisms of expression in
      cultured oesophageal squamous epithelial cells. METHODS: We investigated the
      expression of KLF4 in rat and human Barrett's epithelium specimens, while the
      response of that expression to bile acids was studied using a KLF4 promoter
      luciferase assay. In addition, oesophageal squamous epithelial cells were
      transfected with a KLF4 expression vector, after which their possible
      transformation into intestinal-type epithelial cells was investigated. RESULTS:
      In both rat and human tissues, Barrett's epithelium strongly expressed KLF4.
      Furthermore, a bile acids mixture increased KLF4 promoter activity, and mRNA and
      protein expression in oesophageal epithelial cells. Results from mutation
      analysis of the KLF4 promoter suggested that the NF-kappaB binding site is
      responsible for bile acid-induced activation of the KLF4 promoter. In addition,
      KLF4 and Cdx2 stimulated each other by directly binding to the promoter of the
      other, while transfection of the KLF4 expression vector in oesophageal epithelial
      cells induced production of MUC2 protein. CONCLUSION: Bile acid-induced
      sequential expression of KLF4 followed by MUC2 production may have an important
      role in the development of Barrett's epithelium.

PMID- 21193455
TI  - Nanoliposomal ceramide prevents in vivo growth of hepatocellular carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) affects an increasing
      number of people worldwide. The poor survival rate of patients with HCC is
      manifested by an aggressive and metastatic phenotype, as well as a poor response
      to common therapeutic strategies. The purpose of this study was to evaluate the
      efficacy of nanoliposomal C6-ceramide as an antineoplastic agent in an in vivo
      model of human HCC. METHODS: The growth-arresting and pro-apoptotic properties of
      nanoliposomal C6-ceramide were first evaluated in vitro in human SK-HEP-1 cells
      by assessing cellular viability, caspase 3/7 activity, annexin-V expression, DNA
      fragmentation, cell cycle distribution and AKT phosphorylation. SK-HEP-1 cells
      were then engrafted subcutaneously into athymic nude mice and nanoliposomal C6
      ceramide was administered by tail vein injection. Tumour size was monitored over
      time, followed by excision of tumours to evaluate tumour vascularisation,
      proliferation, apoptosis and cellular signalling. RESULTS: Nanoliposomal C6
      ceramide, but not ghost (no ceramide) nanoliposomes, induced apoptotic cell death
      of SK-HEP-1 cells in vitro, concomitant with an accumulation of cells in the G2
      phase of the cell cycle and decreased phosphorylation of AKT. Systemic
      administration of nanoliposomal C6-ceramide to mice engrafted with SK-HEP-1
      tumours reduced tumour vascularisation and proliferation, induced tumour cell
      apoptosis, decreased phosphorylation of AKT and ultimately blocked tumour growth.
      CONCLUSIONS: These studies show that nanoliposomal ceramide is an efficacious
      antineoplastic agent for the treatment of in vitro and in vivo models of human
      HCC.

PMID- 21193456
TI  - Adult pancreatic acinar cells dedifferentiate to an embryonic progenitor
      phenotype with concomitant activation of a senescence programme that is present
      in chronic pancreatitis.
AB  - OBJECTIVE: Acinar cells display plasticity in vitro and in vivo and can activate
      a variety of differentiation programmes that may contribute to pancreatic
      diseases. The aims were to determine: (1) the differentiation potential of acinar
      cells under conditions which favour stem cell survival, and (2) its relationship
      to the phenotypes acquired by pancreatic epithelial cells in chronic
      pancreatitis. DESIGN: Murine acinar cells were cultured in suspension and their
      molecular phenotype was characterised by qRT-PCR, chromatin immunoprecipitation,
      immunocytochemistry and global transcriptome analysis. These findings were
      compared to the changes occurring in experimental chronic pancreatitis induced by
      pancreatic duct ligation and chronic caerulein administration. RESULTS: Acinar
      cells in suspension culture acquired a dedifferentiated phenotype characteristic
      of pancreatic embryonic progenitors, consisting of the co-expression of Ptf1a and
      Pdx1, presence of an embryonic-type PTF1 transcriptional complex, activation of
      the Notch pathway, and expression of additional pancreatic progenitor cell
      markers such as CpA1, Sox9 and Hnf1b. A senescence programme, associated with
      activation of Ras and ERK signalling, limited the proliferative capacity of the
      cells. A similar progenitor-like phenotype with activation of a senescence
      programme was observed in experimental chronic pancreatitis induced by pancreatic
      duct ligation or repeated caerulein administration, with the concomitant and
      differential activation of proliferation and senescence in distinct cell
      populations. CONCLUSIONS: Acinar cells dedifferentiate into an embryonic
      progenitor-like phenotype upon suspension culture. This is associated with the
      activation of a senescence programme. Both processes take place in experimental
      chronic pancreatitis where senescence may contribute to limit tumour progression.

PMID- 21193457
TI  - Reg4 protects against acinar cell necrosis in experimental pancreatitis.
AB  - Background and aims Reg4 is a recently discovered member of the regenerating gene
      family with distinctive expression profiles in primary cancers. To date, the
      physiological function of Reg4 is poorly understood. Previously, the authors
      found that Reg4 was markedly upregulated during acute pancreatitis (AP). The aim
      of this study was to investigate the role of Reg4 in experimental pancreatitis.
      Methods AP was induced in C57BL/6 mice by administration of either l-arginine or
      caerulein, and Reg4 expression was assessed by immunofluorescence, reverse
      transcriptase (RT)-PCR and western blot analyses. Recombinant human Reg4 protein
      (rReg4), heat-inactivated Reg4, neutralising antibody and vehicle were also
      administered to mice by subcutaneous injection. The severity of AP was determined
      by measuring amylase and lipase activities in the serum and histological grading.
      The effect of rReg4 on cell death was examined and epidermal growth factor
      receptor (EGFR), p-EGFR, Akt, p-Akt, Bcl-2 and Bcl-xL expression were assessed by
      western blot analysis of isolated murine acinar cells treated with l-arginine.
      Results Reg4 mRNA and protein were markedly upregulated during arginine-induced
      pancreatitis. Reg4 was widely expressed in residual acinar cells around the
      islets and regenerating metaplastic epithelium. rReg4 could protect against
      arginine-induced necrosis of acinar cells both in vivo and in vitro. This
      protective effect was also confirmed in the caerulein-induced murine model of AP.
      It was shown that arginine induced expression of Bcl-2 and Bcl-xL, while rReg4
      upregulated Bcl-2 and Bcl-xL expression by activating the EGFR/Akt pathway. The
      upregulation of Bcl-xL correlated inversely with cell necrosis in isolated
      pancreatic acinar cells. Conclusions The data suggest that Reg4 may protect
      against acinar cell necrosis in experimental pancreatitis by enhancing the
      expression of Bcl-2 and Bcl-xL via activation of the EGFR/Akt signalling pathway.

PMID- 21193458
TI  - Management of patients with cirrhosis awaiting liver transplantation.
AB  - The demand for OLT continues to be on the rise with patients spending a long time
      on the waiting list; this not only increases the risk of developing further
      decompensation but also mortality. The complications discussed above may not only
      lead to removal from the waiting list in some cases but also a poorer outcome
      following transplantation. Therefore the appropriate prevention, recognition and
      treatment of the above-mentioned complications of cirrhosis will have a positive
      impact on the outcome before and after liver transplantation.

PMID- 21193459
TI  - Diabetes conveys a higher risk of gastric cancer mortality despite an age
      standardised decreasing trend in the general population in Taiwan.
AB  - BACKGROUND: The association between diabetes and gastric cancer has been rarely
      studied. OBJECTIVE: To investigate gastric cancer mortality trends, the mortality
      rate ratios between patients with diabetes and the general population, and the
      risk factors for gastric cancer mortality in diabetic patients. METHODS: In the
      Taiwanese general population from 1995 to 2006, age-standardised trends of
      gastric cancer mortality were evaluated, followed by calculation of age-sex
      specific mortality rates. A total of 113,347 men with diabetes and 131,573 women
      with diabetes, aged >= 25 years and recruited in 1995-1998, were followed to 2006
      for gastric cancer mortality. Age-sex-specific mortality rate ratios for diabetic
      patients versus the general population were calculated. Cox's regression was used
      to evaluate the risk factors among diabetic patients. RESULTS: A decreasing trend
      of age-standardised gastric cancer mortality in the general population (p <
      0.0001) was observed from 1995 to 2006 for both sexes. A total of 627 diabetic
      men and 422 diabetic women died of gastric cancer, with a calculated mortality
      rate of 72.8 and 40.0 per 100,000 person-years, respectively. Mortality rate
      ratios showed a significantly higher risk in diabetic patients with a magnitude
      most remarkable at the youngest age: 1.52 (1.31-1.77), 1.58 (1.40-1.78) and 4.49
      (3.93-5.12) for >= 75, 65-74 and 25-64 years old, respectively, for men; and 1.58
      (1.32-1.90), 1.95 (1.67-2.27) and 3.65 (3.11-4.28), respectively, for women. In
      the diabetic patients, age and male sex were associated with gastric cancer
      mortality, but diabetes type, insulin use, and smoking were not. Body mass index
      and area of residence did not show consistent association. Diabetes duration was
      significantly predictive when those who died of gastric cancer within 5 years of
      diabetes diagnosis were excluded from analysis. CONCLUSIONS: Despite a decreasing
      age-standardised mortality trend in the general population, diabetic patients
      have a higher risk of gastric cancer mortality and this was most remarkable in
      the youngest age group of 25-64 years.

PMID- 21193461
TI  - High sensitivity of five colorectal screening programmes with faecal
      immunochemical test in the Veneto Region, Italy.
AB  - OBJECTIVE: Although guaiac-based faecal occult blood test screening has been
      shown to be effective in reducing colorectal cancer (CRC) mortality, it has been
      criticised mostly for its low sensitivity. Italian CRC screening programmes are
      based on immunochemical tests (iFOBT). We collected and analysed the interval
      cancers (ICs) found by five screening programmes to estimate their sensitivity.
      METHODS: ICs were identified in subjects who had a negative result in a screening
      examination from 2002 to 2007 (N=267,789); data were linked with 2002-2008
      hospital discharge records. Analysis was based on the follow up of 468,306 person
      years. The proportional incidence-based sensitivity was estimated overall and by
      sex, age class, time since last negative iFOBT result, anatomical site, and
      history of screening (first or subsequent test). RESULTS: Overall, 126 ICs were
      identified, compared to 572 expected cancers. The proportional incidences were
      15.3% and 31.0% in the first and the second interval-years, respectively, with an
      overall episode sensitivity of 78.0% (95% CI: 73.8 to 81.6). Sensitivity was
      higher for males than females (80.1% vs 74.8%); no differences were observed by
      age, anatomical site or between programmes. The test sensitivity of iFOBT was
      82.1% (95% CI 78.1% to 85.3%). CONCLUSIONS: iFOBT-based screening programmes
      showed a high performance in terms of sensitivity as estimated through the IC
      rates. The screening schedule utilised in our programmes (single iFOBT,
      positivity threshold of 100 ng Hb/ml of sample solution, inter-screening interval
      of 2 years) shows low rates of missed cancers that are diagnosed during the
      interval. HDR are a convenient and reliable source of data for IC studies.

PMID- 21193460
TI  - Diagnostic value of confocal laser endomicroscopy for gastric superficial
      cancerous lesions.
AB  - BACKGROUND: The identification of gastric superficial cancerous lesions based on
      conventional white-light endoscopy (WLE) is challenging, and histological
      analysis remains the 'gold standard' for the final diagnosis. Confocal laser
      endomicroscopy (CLE) can provide in vivo histological observation without the
      need for biopsy. OBJECTIVE: To develop and evaluate CLE imaging criteria for
      gastric superficial cancerous lesions and to compare the diagnostic value of real
      time integrated CLE (iCLE) and WLE alone in distinguishing gastric superficial
      cancerous lesions. DESIGN: Prospective study. SETTING: Qilu Hospital, Shandong
      University, Jinan, China. PATIENTS: A total of 182 patients were enrolled into
      phase I and 1786 patients were enrolled into phase II. INTERVENTIONS: CLE images
      were blindly evaluated after endoscopy in phase I, and real-time iCLE diagnosis
      during endoscopy was compared with WLE diagnosis by using histopathology as a
      gold standard in phase II. MAIN OUTCOME MEASUREMENTS: The validity and
      reliability of the CLE diagnosis for identifying gastric superficial cancerous
      lesions. RESULTS: Off-line CLE diagnosis for early gastric cancers had a high
      sensitivity (88.1%) and specificity (98.6%). When the two-tiered CLE
      classification of non-cancerous lesions and cancer/high-grade intraepithelial
      neoplasia (HGIN) lesions was introduced, CLE diagnosis led to a higher
      sensitivity (90.2%) and specificity (98.5%) (phase I). Real-time iCLE diagnosis
      had a higher sensitivity (88.9%), specificity (99.3%) and accuracy (98.8%) for
      gastric superficial cancer/HGIN lesions than WLE diagnosis (sensitivity, 72.2%;
      specificity, 95.1%; and accuracy, 94.1%) (p < 0.05) (phase II). Limitations This
      was a single-centre study. CONCLUSIONS: CLE can be used to identify gastric
      superficial cancer/HGIN lesions with high validity and reliability.

PMID- 21193462
TI  - Trends in management of phlegmasia cerulea dolens.
AB  - Phlegmasia cerulea dolens (PCD) is a fulminant condition of acute massive venous
      thrombosis that may result in major amputation or death unless treated in an
      early phase. Guidelines for treatment are still not clearly documented. As a
      consequence, physicians might have limited knowledge of this potential life
      threatening condition and its clinical course. Therefore, the purpose of this
      review was to analyze and summarize clinical manifestations and proposed
      diagnostic approach, factors that affect the outcome of PCD, and the evolution of
      management and therapeutic options. Underlying malignancy, pulmonary embolism,
      and PCD severity are the vital factors that predict the outcome of PCD. In the
      last decades, treatment options have remained largely unchanged. Published
      evidence shows that advances in minimally invasive techniques have not yet
      resulted in outcome improvements compared with traditional surgical thrombectomy.
      Treatment seems to depend on grading the severity of this condition and
      experience of the surgeon.

PMID- 21193463
TI  - Recurrent neurogenic thoracic outlet syndrome stressing the importance of
      pectoralis minor syndrome.
AB  - BACKGROUND: Although first described over 60 years ago, neurogenic pectoralis
      minor syndrome (NPMS) has only recently been noted to be present in over half the
      patients with a clinical diagnosis of neurogenic thoracic outlet syndrome (NTOS).
      Similarly, NPMS has also been observed in the majority of patients with recurrent
      NTOS. This study explores the role of pectoralis minor tenotomy (PMT) in patients
      with recurrent NTOS. METHODS: A total of 86 patients with symptoms of recurrent
      NTOS, who had failed to improve on conservative management, were evaluated by
      history and physical examination for both NPMS and NTOS. Diagnostic tests
      included pectoralis minor muscle (PMM) blocks, scalene muscle blocks, and medial
      antebrachial cutaneous nerve (MAC) measurements. Surgery was either PMT alone or
      PMT plus brachial plexus decompression (BPD). Follow-up was 1 to 3 years.
      RESULTS: All patients had multiple symptoms of pain, weakness, and paresthesia.
      Patients who qualified for PMT alone had slightly fewer symptoms than those who
      required PMT plus BPD. There was essentially no difference in physical findings
      between the 2 groups. It was the response to PMM blocks and scalene muscle blocks
      that determined which of the 2 operations was performed. Pectoralis minor
      tenotomy alone gave 69% good results in 65 operations, with 8% fair and 23%
      failures. Pectoralis minor tenotomy plus BPD in 39 operations gave 58% good
      improvement, 20% fair and 22% failures. CONCLUSION: All patients with recurrent
      NTOS should be evaluated clinically for NPMS. If patients complain of pain or
      tenderness in the anterior chest wall and axilla, a diagnostic PMM block should
      be performed. A good response to the block suggests that consideration be given
      to performing PMT alone as it a simple, low-risk outpatient procedure. If
      unsuccessful, BPD can be performed at a later date. If there is a poor response
      to the PMM block, BPD is indicated along with PMT, provided there were some
      symptoms of NPMS.

PMID- 21193464
TI  - Increasing the proportion of autologous arteriovenous fistulas does not diminish
      fistula patency.
AB  - OBJECTIVE: Arteriovenous fistulas (AVF) constructed before and after initiating
      the kidney disease outcomes and quality initiative (KDOQI) guidelines were
      reviewed at a single academic center to identify decreased patency with use of
      potentially inferior vein conduits. METHODS: Primary access procedures performed
      pre- and post-adoption of KDOQI guidelines were compared for the primary outcomes
      of maturation rate and primary patency and the secondary outcome of access
      utilization. RESULTS: The proportion of autologous AVFs created was higher post
      KDOQI (73% vs 35%, P < .001), and an increased use of the basilic vein was
      observed (20% vs 2%, P < .05). The failure rate of fistula maturation was reduced
      post-KDOQI (24% vs 38%, P < .05); however, access utilization was also decreased
      (59% vs 75%, P < .001). CONCLUSIONS: Adherence to KDOQI guidelines for AVFs does
      not compromise fistula patency and increased use of the basilic vein may lead to
      superior fistula maturation rates. Early referral may result in lower fistula
      utilization rates, however.

PMID- 21193465
TI  - Thrombospondin 1, fibronectin, and vitronectin are differentially dependent upon
      RAS, ERK1/2, and p38 for induction of vascular smooth muscle cell chemotaxis.
AB  - BACKGROUND: Thrombospondin 1 (TSP-1), fibronectin (Fn), and vitronectin (Vn)
      promote vascular smooth muscle cell (VSMC) chemotaxis through a variety of second
      messenger systems, including Ras, ERK1/2, and p38. HYPOTHESIS: Ras, ERK1/2, and
      p38 differentially affect TSP-1-, Fn-, and Vn-induced VSMC chemotaxis. METHODS:
      Bovine VSMCs were transfected with Ras N17 or treated with the following
      inhibitors: a farnesyl protein transferase (FPT) inhibitor, PD098059 (ERK1/2
      inhibitor), or SB202190 (p38 inhibitor). Thrombospondin 1, Fn, and Vn were used
      as chemoattractants. Results were analyzed by analysis of variance (ANOVA) with
      post hoc testing (P < .05). RESULTS: Ras N17 transfection or FPT inhibitor
      treatment inhibited TSP-1-, Fn-, and Vn-induced chemotaxis. PD098059 or SB202190
      resulted in more inhibition of VSMC migration to TSP-1 than to Fn or Vn.
      CONCLUSIONS: Ras appears equally relevant in the signal transduction pathways of
      TSP-1-, Fn-, and Vn-induced VSMC chemotaxis. Thrombospondin 1-induced migration
      is more dependent upon ERK1/2 and p38 than Fn- or Vn-included migration.

PMID- 21193466
TI  - Endovascular treatment of an innominate artery iatrogenic pseudoaneurysm
      following subclavian vein catheterization.
AB  - Central venous catheterization is routinely required in a wide range of clinical
      situations such as hemodynamic monitoring, delivery of blood products and drugs,
      hemodialysis, total parental nutrition, and management of perioperative fluids.
      Pseudoaneurysms account for 4% of all innominate artery aneurysms. Clinical
      presentation may include airway and neurological compression, chest pain,
      mediastinal syndrome, upper limb ischemia, and hemodynamic instability. We report
      what we believe is the first documented case of a successful endovascular stent
      graft repair of an innominate artery iatrogenic pseudoaneurysm.

PMID- 21193467
TI  - Nonrecurrent inferior laryngeal nerve.

PMID- 21193469
TI  - Dynamics of extravascular pulmonary water and intracranial pressure in patients
      with ischemic stroke.
AB  - The objective of the present study was to examine the relationship among
      extravascular pulmonary water, intracranial and cerebral perfusion pressure,
      hemodynamic parameters (eg, cardiac index, system vascular resistance index), and
      brain stem function during acute ischemic stroke. The subjects were 17 comatose
      patients with ischemic stroke who were admitted to an intensive care unit. The
      results revealed an elevation in extravascular lung water in the absence of
      cardiac dysfunction. The absence of correlation between indices of brain vascular
      resistance and mean arterial pressure confirmed that a disturbance of cerebral
      blood flow was present. There was a correlation between auditory-evoked potential
      parameters and extravascular lung water during the study period. The correlation
      between auditory-evoked potentials and extravascular lung water may imply that
      ischemic brainstem injury plays a significant role in the development of
      increased pulmonary capillary permeability and the elevation of extravascular
      lung water. Brain stem injury is a cause of noncardiogenic lung edema in comatose
      patients following acute ischemic stroke.

PMID- 21193470
TI  - Diagnosis of acute respiratory distress syndrome in nosocomial pneumonia.
AB  - Acute respiratory distress syndrome (ARDS) complicates nosocomial pneumonias
      (NPn) in 12% to 33% of patients with associated increases in mortality of up to
      80%. A timely diagnosis of ARDS with NPn is, however, problematic. The aim of
      this investigation was to improve the diagnosis and treatment of the early stages
      of ARDS with NPn. A total of 82 cancer and multiple trauma patients were enrolled
      in the investigation. Patients were split into 3 groups according to standard
      ARDS and NPn diagnostic criteria: group 1 ("ARDS + NPn"), group 2 ("NPn"), group
      3 ("no ARDS, no NPn"). ARDS was diagnosed using 3 methods: the Murray score, the
      American-European Consensus Conference criteria, and the V. A. Negovsky Research
      Institute of General Reanimatology criteria. Elevation of extravascular lung
      water index along with other ARDS diagnostic criteria (oxygenation index, central
      hemodynamic indices) was predictive of early stage of ARDS in patients with NPn.
      The standard diagnostic criteria for ARDS, including the Murray score,
      oxygenation index, and radiographic data only predicted the later stages of ARDS
      in NPn. Early diagnosis of ARDS with concomitant NPn in the current study was
      associated with improved treatment results with decreased duration of artificial
      ventilation and intensive care unit stay.

PMID- 21193471
TI  - Efficacy of alveolar recruitment maneuvers in patients with complicated thoracic
      trauma.
AB  - The objective of this study was to measure the efficacy of biphasic positive
      airway pressure (BIPAP) and synchronized intermittent mandatory ventilation
      (SIMV) with alveolar recruitment maneuvers (ARMs) in patients with acute lung
      injury (ALI) and concomitant pneumothorax. Seventy-four patients with ALI and
      concomitant pneumothorax secondary to blunt thoracic injury were studied. All
      patients fulfilled criteria for the first stage of acute respiratory distress
      syndrome, which consisted of acute onset dyspnea, isolated rales, an
      extravascular lung water index >7 mL/kg, and an oxygenation index <300 mm Hg in
      the absence of left-ventricular dysfunction. After evacuation of the
      pneumothorax, ARMs were performed using BIPAP or SIMV 3 to 5 times a day with a
      peak pressure of 33.4 +/- 0.2 cm H(2)O and a positive end-expiratory pressure of
      16.1 +/- 0.2 cm H(2)O. The use of BIPAP in patients with ALI and concomitant
      pneumothorax reduced the time to resolution of the air leak allowing application
      of earlier ARMs. ARMs with peak pressures of 35 to 40 cm H(2)O effectively
      improved oxygenation and biomechanical properties of the lungs and did not cause
      pneumothorax relapse. In conclusion, BIPAP allowed for spontaneous ventilation
      during the breathing cycle and limited P (peak). Its use was associated with more
      rapid sealing of air leaks with the ability to conduct earlier ARMs. The use of
      BIPAP compared with SIMV improved outcome in the presence of complex thoracic
      trauma.

PMID- 21193472
TI  - Macro- and microstructure of erythrocyte membranes under acute massive hemorrhage
      and subsequent blood reinfusion.
AB  - The authors studied changes in erythrocyte membrane nanostructure using a rodent
      model of hemorrhagic hypotension and resuscitation. Both macro- and
      microstructural elements were examined using atomic force microscopy. Membrane
      "roughness" was characterized using spatial Fourier transformation and was
      stratified according to the periodicity of the membrane. Acute hemorrhage
      resulted in an increase in the diameter and height of erythrocytes, which
      returned to baseline levels by the end of the hemorrhagic hypotensive period. The
      effect of hypotension on the erythrocyte surface was nonuniform. In those regions
      where damage was considerable, the rate of restoration of the membrane
      microstructure to baseline levels was prolonged. The less damaged surfaces were
      restored more rapidly to control values after reperfusion. More detailed use of
      atomic force microscopy in the definition of the erythrocyte membrane
      microstructure may further define the mechanisms of cellular functional
      restoration after hemorrhage.

PMID- 21193473
TI  - Plasmid-mediated carbapenem-hydrolysing beta-lactamase KPC-2 in a Klebsiella
      pneumoniae isolate from Switzerland.

PMID- 21193474
TI  - Molecular characterization and phylogenetic analysis of quinolone resistance
      determining regions (QRDRs) of gyrA, gyrB, parC and parE gene loci in viridans
      group streptococci isolated from adult patients with cystic fibrosis.
AB  - OBJECTIVES: Ciprofloxacin is the most frequently used member of the
      fluoroquinolones during initial eradication therapy of Pseudomonas aeruginosa, as
      well as during acute pulmonary exacerbations. However, its long-term effect on
      the susceptibility of the commensal flora within the cystic fibrosis (CF) airways
      has not yet been examined. The aim of this study was therefore to examine the
      consequence of oral ciprofloxacin usage on the resistance of the commensal
      viridans group streptococci (VGS), in terms of MICs and mutational analysis of
      the quinolone resistance-determining regions (QRDRs). METHODS: The MICs of
      ciprofloxacin, efflux activities and amino acid substitutions in the QRDRs for
      190 isolates of VGS, originating from the sputa of adult CF patients who had been
      exposed constantly to ciprofloxacin, were examined. VGS organisms included
      Streptococcus salivarius, Streptococcus mitis, Streptococcus sanguinis,
      Streptococcus oralis, Streptococcus parasanguinis, Streptococcus infantis,
      Streptococcus gordonii, Streptococcus anginosus, Streptococcus cristatus,
      Streptococcus australis and Streptococcus mutans. Ciprofloxacin susceptibility
      was determined by broth microdilution and QRDRs within the gyrA, gyrB, parC and
      parE gene loci were explored using sequence analysis. RESULTS: Twenty-seven
      (14.2%) streptococcal isolates were resistant to ciprofloxacin (MICs >=8 mg/L)
      and 21 (11.1%) had reduced susceptibility (MICs 4 mg/L). As a comparator,
      clinically non-significant and non-invasive VGS organisms were examined in 12
      consecutive non-CF patients in the community, where no resistance to
      ciprofloxacin was observed. Five novel QRDR PCR assays were developed to
      elucidate mutations within the CF VGS population, where there were six positions,
      which corresponded to previously reported quinolone resistance responsible
      mutations, and eight novel potential QRDR resistance mutations. Double mutations
      in gyrA and parC/parE led to MICs of 16 to >64 mg/L, while single mutations in
      parC or parE resulted in MICs of 8-32 mg/L and 8 mg/L, respectively. The mean
      homologies of each species to Streptococcus pneumoniae R6 were: gyrA, 70.3%-95%;
      gyrB, 69.6%-96.2%; parC, 76.1%-94.8%; and parE, 70.7%-94.7%. The close relatives
      of S. pneumoniae, S. mitis and S. oralis, showed high similarity for all four
      genes (more than 86%). CONCLUSIONS: Treatment of P. aeruginosa with oral
      ciprofloxacin in patients with CF may concurrently reduce antibiotic
      susceptibility in the commensal VGS flora, where these organisms may potentially
      act as a reservoir of fluoroquinolone resistance gene determinants for newly
      acquired and antibiotic-susceptible pathogens, particularly the Streptococcus
      milleri group.

PMID- 21193475
TI  - Bacteraemia due to multidrug-resistant Gram-negative bacilli in cancer patients:
      risk factors, antibiotic therapy and outcomes.
AB  - OBJECTIVES: To assess the risk factors, antibiotic therapy and outcomes of
      multidrug-resistant Gram-negative bacilli (MDRGNB) bacteraemia in hospitalized
      patients with cancer. METHODS: Episodes of MDRGNB bacteraemia were compared with
      a susceptible control group in a 4 year prospective study. RESULTS: Of 747
      bacteraemias, 372 (49.7%) were caused by a Gram-negative bacilli (GNB). Fifty-one
      of these (13.7%) were caused by a multidrug-resistant (MDR) strain. Previous
      antibiotics [odds ratio (OR) 3.57; 95% confidence interval (CI) 1.63-7.80] and
      urinary catheter (OR 2.41; 95% CI 1.01-5.74) were identified as independent risk
      factors for MDRGNB acquisition. The most frequent mechanism of resistance was
      extended-spectrum beta-lactamase (ESBL) production (45%), mainly by Escherichia
      coli, followed by Amp-C cephalosporinase hyperproduction (24%). Patients with
      MDRGNB bacteraemia more frequently received inadequate initial antibiotic therapy
      (69% versus 9%; P < 0.001) and time to adequate therapy was longer in this group
      (41% versus 4%; P < 0.001). Patients in the resistant group more frequently
      required intensive care unit (ICU) admission (14% versus 5%; P = 0.023), had
      greater need for mechanical ventilation (14% versus 3%; P = 0.005) and had a
      higher overall case-fatality rate (41% versus 21%; P = 0.003). Risk factors for
      mortality were solid tumour (OR 5.04; 95% CI 2.49-10.19), current corticosteroid
      use (OR 4.38; 95% CI 2.39-8.05), ICU admission (OR 11.40; 95% CI 3.19-40.74) and
      MDRGNB bacteraemia (OR 3.52; 95% CI 1.36-9.09). CONCLUSIONS: MDRGNB bacteraemia
      was common among cancer patients, especially in those exposed to antibiotics and
      urinary catheter. The most frequent mechanism of resistance was ESBL production.
      Patients with MDRGNB more frequently received inadequate empirical antibiotic
      therapy and presented poorer outcomes with a higher overall case-fatality rate
      (within 30 days).

PMID- 21193476
TI  - Serotypes and genotypes of Streptococcus pneumoniae causing pneumonia and acute
      exacerbations in patients with chronic obstructive pulmonary disease.
AB  - OBJECTIVES: This study aimed to compare the antibiotic susceptibilities,
      serotypes and genotypes of pneumococci causing pneumonia or acute exacerbations
      of chronic obstructive pulmonary disease (AECOPD) in patients with COPD. METHODS:
      A total of 611 pneumococci collected from 487 COPD patients with pneumonia (n =
      255, 94 bacteraemic pneumonia) or AECOPD episodes (n = 356), from 2001 to 2008,
      were analysed. Antibiotic susceptibility was studied by microdilution. Serotypes
      (PCR or Quellung) and genotypes (PFGE and multilocus sequence typing) were
      determined. RESULTS: Pneumococci isolated from AECOPD episodes were significantly
      more resistant to co-trimoxazole and chloramphenicol than those isolated from
      pneumonia episodes (39.0% versus 29.7% and 13.8% versus 8.2%, respectively, P <
      0.05). Comparing serotypes of isolates causing bacteraemic pneumonia, non
      bacteraemic pneumonia and AECOPD, serotypes 4, 5 and 8 were associated with
      bacteraemic pneumonia (P < 0.05), serotypes 1 and 3 were associated with
      bacteraemic and non-bacteraemic pneumonia (P < 0.05) and serotypes 16F and 11A
      and non-typeable pneumococci were associated with AECOPD episodes (P < 0.05). The
      genotypes related to serotypes 3 (Netherlands(3)-ST180 and ST260(3)), 1
      (Sweden(1)-ST306), 5 (Colombia(5)-ST289) and 8 (Netherlands(8)-ST53) were
      isolated more frequently in pneumonia episodes (P < 0.05), whereas genotype
      ST30(16F) (serotype 16F) was more frequently recovered from AECOPD episodes.
      CONCLUSIONS: In our experience, serotype 3 pneumococci (Netherlands(3)-ST180 and
      ST260(3) genotypes) commonly cause pneumonia and acute exacerbations in COPD
      patients. Pneumococci of serotypes 1 (Sweden(1)-ST306), 4 (ST247(4)), 5
      (Colombia(5)-ST289) and 8 (Netherlands(8)-ST53) were more often associated with
      pneumonia. Non-typeable pneumococci may play an important role in acute
      exacerbations.

PMID- 21193477
TI  - Comment on: Spondylodiscitis: update on diagnosis and management.

PMID- 21193478
TI  - Single-port laparoscopic cholecystectomy with the x-cone: a feasibility study in
      9 pigs.
AB  - OBJECTIVE: Virtually any port system for single-port laparoscopic surgery is for
      single usage only. The aim of this study was to trial the novel and completely
      reusable port X-Cone in order to perform a cholecystectomy by one infraumbilical
      incision. METHODS: Single access cholecystectomies were performed in 9
      anesthetized domestic pigs in nonsurvival studies. Only one infraumbilical
      incision was performed for placing the reusable, multichannel steel port system.
      A newly developed angulated forceps was used besides regularly used instruments
      in laparoscopic surgery. RESULTS: The gallbladder was successfully removed in 9
      pigs. At postmortem examination, the clips placed on the cystic duct and the
      cystic artery. No bile leakage was found at the operative field. CONCLUSION:
      Single-port cholecystectomy with the reusable X-Cone single-port system is safe
      and feasible. No additional incisions were needed. The system is ergonomically
      designed, easy to handle, and the learning curve for cholecystectomy is steep.

PMID- 21193479
TI  - Fixation of intestinal tissue using a novel endoscopic device.
AB  - INTRODUCTION: The purpose of this study was to assess the utility and strength of
      a novel endoscopic fixation device, Brace-Bar, in the large intestine and compare
      the strength with other currently available techniques. The primary outcome was
      the strength of fixation using 3 endoscopic methods: BraceBar, suture, and
      commercially available tackers. The hypothesis is that the use of the BraceBar
      will result in fixation strength similar to the strength of the other methods.
      MATERIALS AND METHODS: An ex vivo porcine model was used to test 3 fixation
      methods: Group 1, BraceBar (Prototype); Group 2, ProTack (AutoSuture); and Group
      3, TI-CRON suture (Syneture). Large-bowel segments were fixed to abdominal wall
      tissue at 20 cm from the distal end of the rectum. Primary endpoint was pull away
      strength. A total of 45 trials of each method were performed. Comparison between
      the groups was done using JMP 7.0. RESULTS: There was no significant difference
      in strength between the BraceBar group and the suture group ( P = .1236). The
      BraceBar method demonstrated significantly higher strength compared with the
      tacker group (P = .003). CONCLUSION: Use of the BraceBar for fixation of the
      large bowel is at least comparable with suture fixation, making clinical use of
      BraceBar a reasonable consideration. Use of this device may make endoscopic
      repair of certain intestinal conditions feasible.

PMID- 21193480
TI  - Evolutionary diversification and geographical isolation in Dubautia laxa
      (Asteraceae), a widespread member of the Hawaiian silversword alliance.
AB  - BACKGROUND AND AIMS: The Hawaiian silversword alliance (Asteraceae) is one the
      best examples of a plant adaptive radiation, exhibiting extensive morphological
      and ecological diversity. No research within this group has addressed the role of
      geographical isolation, independent of ecological adaptation, in contributing to
      taxonomic diversity. The aims of this study were to examine genetic
      differentiation among subspecies of Dubautia laxa (Asteraceae) to determine if
      allopatric or sympatric populations and subspecies form distinct genetic clusters
      to understand better the role of geography in diversification within the
      alliance. METHODS: Dubautia laxa is a widespread member of the Hawaiian
      silversword alliance, occurring on four of the five major islands of the Hawaiian
      archipelago, with four subspecies recognized on the basis of morphological,
      ecological and geographical variation. Nuclear microsatellites and plastid DNA
      sequence data were examined. Data were analysed using maximum-likelihood and
      Bayesian phylogenetic methodologies to identify unique evolutionary lineages. KEY
      RESULTS: Plastid DNA sequence data resolved two highly divergent lineages,
      recognized as the Laxa and Hirsuta groups, that are more similar to other members
      of the Hawaiian silversword alliance than they are to each other. The Laxa group
      is basal to the young island species of Dubautia, whereas the Hirsuta group forms
      a clade with the old island lineages of Dubautia and with Argyroxiphium. The
      divergence between the plastid groups is supported by Bayesian microsatellite
      clustering analyses, but the degree of nuclear differentiation is not as great.
      Clear genetic differentiation is only observed between allopatric populations,
      both within and among islands. CONCLUSIONS: These results indicate that
      geographical separation has aided diversification in D. laxa, whereas
      ecologically associated morphological differences are not associated with neutral
      genetic differentiation. This suggests that, despite the stunning ecological
      adaptation observed, geography has also played an important role in the Hawaiian
      silversword alliance plant adaptive radiation.

PMID- 21193481
TI  - S-RNase-based self-incompatibility in Petunia inflata.
AB  - BACKGROUND: For the Solanaceae-type self-incompatibility, also possessed by
      Rosaceae and Plantaginaceae, the specificity of self/non-self interactions
      between pollen and pistil is controlled by two polymorphic genes at the S-locus:
      the S-locus F-box gene (SLF or SFB) controls pollen specificity and the S-RNase
      gene controls pistil specificity. SCOPE: This review focuses on the work from the
      authors' laboratory using Petunia inflata (Solanaceae) as a model. Here, recent
      results on the identification and functional studies of S-RNase and SLF are
      summarized and a protein-degradation model is proposed to explain the biochemical
      mechanism for specific rejection of self-pollen tubes by the pistil. CONCLUSIONS:
      The protein-degradation model invokes specific degradation of non-self S-RNases
      in the pollen tube mediated by an SLF, and can explain compatible versus
      incompatible pollination and the phenomenon of competitive interaction, where SI
      breaks down in pollen carrying two different S-alleles. In Solanaceae,
      Plantaginaceae and subfamily Maloideae of Rosaceae, there also exist multiple S
      locus-linked SLF/SFB-like genes that potentially function as the pollen S-gene.
      To date, only three such genes, all in P. inflata, have been examined, and they
      do not function as the pollen S-gene in the S-genotype backgrounds tested.
      Interestingly, subfamily Prunoideae of Rosaceae appears to possess only a single
      SLF/SFB gene, and competitive interaction, observed in Solanaceae, Plantaginaceae
      and subfamily Maloideae, has not been observed. Thus, although the cytotoxic
      function of S-RNase is an integral part of SI in Solanaceae, Plantaginaceae and
      Rosaceae, the function of SLF/SFB may have diverged. This highlights the
      complexity of the S-RNase-based SI mechanism. The review concludes by discussing
      some key experiments that will further advance our understanding of this self/non
      self discrimination mechanism.

PMID- 21193482
TI  - Phylogeographic patterns, genetic affinities and morphological differentiation
      between Epipactis helleborine and related lineages in a Mediterranean glacial
      refugium.
AB  - BACKGROUND AND AIMS: In the Mediterranean basin, the Italian peninsula has been
      suggested to be one of the most important glacial refugia for temperate tree
      species. The orchid genus Epipactis is widely represented in the Italian
      peninsula by widespread species and several endemic, localized taxa, including
      selfing and outcrossing taxa. Here the phylogenetic and phylogeographic
      relationships in a group of closely related taxa in Epipactis are investigated
      with the aim of understanding the role of this refugial area for cladogenesis and
      speciation in herbaceous species, such as terrestrial orchids. METHODS: Ribosomal
      DNA (rDNA) was employed to assess phylogenetic relationships, and plastid
      sequence variation in the rbcL-accD spacer was used to reveal phylogeographic
      patterns among plastid haplotypes using a parsimony network. KEY RESULTS: Low
      genetic variation and shared ribotypes were detected in rDNA, whereas high levels
      of sequence variation and a strong phylogeographic structure were found in the
      examined plastid region. The parsimony plastid haplotype network identified two
      main haplotype groups, one including E.
      atrorubens/microphylla/muelleri/leptochila and the other including all accessions
      of E. helleborine and several localized and endemic taxa, with a combination of
      widespread and rare haplotypes detected across the Italian peninsula. A greater
      genetic divergence separated the Italian and other European accessions of E.
      helleborine. CONCLUSIONS: Phylogenetic and phylogeographic patterns support a
      working hypothesis in which the Italian peninsula has only recently been
      colonized by Epipactis, probably during the most recent phase of the Quaternary
      age and, nevertheless, it acted as a remarkable centre of diversification for
      this orchid lineage. Changes in pollination strategy and recurrent shifts in
      mating system (from allogamy to autogamy) could have represented the mechanism
      promoting this rapid diversification and the observed high taxonomic complexity
      detected in the E. helleborine species complex.

PMID- 21193484
TI  - Valvular heart disease associated with benfluorex therapy: results from the
      French multicentre registry.
AB  - AIMS: The aim of this paper is to report clinical characteristics, consequences,
      echocardiographic features, and pathological findings encountered in patients
      suffering from valvular disease associated with benfluorex exposure in a
      multicentre French registry. METHODS AND RESULTS: Forty patients suffering from
      unexplained restrictive valvular disease with a previous exposition to
      benfluorex, a fenfluramine derivative, were identified from eight French
      university hospitals. Patients were mostly women (87.5%) with a mean age of 57 +/
      9 years and high body mass index of 30 +/- 7 kg/m2; 37.5% of them presented with
      severe heart failure symptoms (NYHA class III and IV). Benfluorex mean daily dose
      was 415 +/- 131 mg with total therapy duration of 72 +/- 53 months. Resulting
      cumulative dose was 910 +/- 675 g. Common echocardiographic findings were
      leaflets and sub-valvular apparatus thickening and retraction. Aortic and mitral
      valve regurgitations resulting from leaflets loss of coaptation were the most
      frequent findings (87.5 and 82.5%) and were severe in 29 patients (72.5%).
      Multiple valve involvements were present in 31 cases (77.5%). Pulmonary arterial
      hypertension was identified in 20 cases (50%). Histopathological examination
      demonstrated abundant extra cellular matrix encasing the leaflets without
      modification of valve architecture. Fifteen patients (37.5%) underwent valvular
      surgery. CONCLUSION: Benfluorex-related valvulopathy shares numerous
      characteristics with other drug-induced valvular disease. Clinical consequences
      may be serious with severe heart failure symptoms that may lead to surgical
      treatment.

PMID- 21193483
TI  - Benfluorex: the last chapter of drug-induced valvular heart disease?

PMID- 21193485
TI  - Contrast transoesophageal echocardiography remains superior to contrast-enhanced
      cardiac magnetic resonance imaging for the diagnosis of patent foramen ovale.
AB  - AIMS: In 30-40% of patients with acute ischaemic stroke, the cause remains
      undefined (cryptogenic stroke). Contrast transoesophageal echocardiography (TEE)
      is considered the gold standard for patent foramen ovale (PFO) detection.
      Recently, however, cardiac magnetic resonance (CMR) has also been applied to
      detect PFO. In this study, we compared the diagnostic value of CMR and TEE in
      detecting PFO in a group of patients with apparently cryptogenic stroke. METHODS
      AND RESULTS: Twenty-five patients (age 50 +/- 13 years, 16 males) with apparently
      cryptogenic ischaemic stroke underwent contrast-enhanced TEE and contrast CMR for
      detection of possible PFO. Both imaging studies were performed during Valsalva
      manoeuvre. PFO grading results were assessed visually both for TEE and for CMR,
      according to the entity of contrast passage in the left atrium (grade 0 = no PFO;
      grades 1, 2, and 3 = mild, medium, and wide PFO, respectively). TEE detected PFO
      in 16 patients (64%). Contrast-enhanced CMR identified a PFO in 7 (44%) of these
      patients. TEE showed a grade 1 PFO in five patients, a grade 2 PFO in eight
      patients, and a grade 3 PFO in three patients. Of these patients, CMR failed to
      identify PFO in all five patients with a grade 1 PFO, in one patient with a grade
      2 PFO, and one patient with grade 3 PFO according to TEE. None of the nine
      patients without PFO at TEE was shown to have a PFO at CMR. When compared with
      TEE, the present methodology of CMR had a sensitivity of 50%, specificity of
      100%, negative predictive value of 31%, and a positive predictive value of 100%.
      CONCLUSION: Our data suggest that TEE is the cornerstone imaging diagnostic test
      to detect and characterize PFO in patients with ischaemic stroke, and is shown to
      be better compared with the current CMR sequences.

PMID- 21193486
TI  - White matter damage and cognitive impairment after traumatic brain injury.
AB  - White matter disruption is an important determinant of cognitive impairment after
      brain injury, but conventional neuroimaging underestimates its extent. In
      contrast, diffusion tensor imaging provides a validated and sensitive way of
      identifying the impact of axonal injury. The relationship between cognitive
      impairment after traumatic brain injury and white matter damage is likely to be
      complex. We applied a flexible technique-tract-based spatial statistics-to
      explore whether damage to specific white matter tracts is associated with
      particular patterns of cognitive impairment. The commonly affected domains of
      memory, executive function and information processing speed were investigated in
      28 patients in the post-acute/chronic phase following traumatic brain injury and
      in 26 age-matched controls. Analysis of fractional anisotropy and diffusivity
      maps revealed widespread differences in white matter integrity between the
      groups. Patients showed large areas of reduced fractional anisotropy, as well as
      increased mean and axial diffusivities, compared with controls, despite the small
      amounts of cortical and white matter damage visible on standard imaging. A
      stratified analysis based on the presence or absence of microbleeds (a marker of
      diffuse axonal injury) revealed diffusion tensor imaging to be more sensitive
      than gradient-echo imaging to white matter damage. The location of white matter
      abnormality predicted cognitive function to some extent. The structure of the
      fornices was correlated with associative learning and memory across both patient
      and control groups, whilst the structure of frontal lobe connections showed
      relationships with executive function that differed in the two groups. These
      results highlight the complexity of the relationships between white matter
      structure and cognition. Although widespread and, sometimes, chronic
      abnormalities of white matter are identifiable following traumatic brain injury,
      the impact of these changes on cognitive function is likely to depend on damage
      to key pathways that link nodes in the distributed brain networks supporting high
      level cognitive functions.

PMID- 21193487
TI  - Regulation of nucleotide excision repair activity by transcriptional and post
      transcriptional control of the XPA protein.
AB  - The XPA (Xeroderma pigmentosum A) protein is one of the six core factors of the
      human nucleotide excision repair system. In this study we show that XPA is a rate
      limiting factor in all human cell lines tested, including a normal human
      fibroblast cell line. The level of XPA is controlled at the transcriptional level
      by the molecular circadian clock and at the post-translational level by a HECT
      domain family E3 ubiquitin ligase called HERC2. Stabilization of XPA by
      downregulation of HERC2 moderately enhances excision repair activity. Conversely,
      downregulation of XPA by siRNA reduces excision repair activity in proportion to
      the level of XPA. Ubiquitination and proteolysis of XPA are inhibited by DNA
      damage that promotes tight association of the protein with chromatin and its
      dissociation from the HERC2 E3 ligase. Finally, in agreement with a recent
      report, we find that XPA is post-translationally modified by acetylation.
      However, contrary to the previous claim, we find that in mouse liver only a small
      fraction of XPA is acetylated and that downregulation of SIRT1 deacetylase in two
      human cell lines does not affect the overall repair rate. Collectively, the data
      reveal that XPA is a limiting factor in excision repair and that its level is
      coordinately regulated by the circadian clock, the ubiquitin-proteasome system
      and DNA damage.

PMID- 21193488
TI  - The suboptimal structures find the optimal RNAs: homology search for bacterial
      non-coding RNAs using suboptimal RNA structures.
AB  - Non-coding RNAs (ncRNAs) are regulatory molecules encoded in the intergenic or
      intragenic regions of the genome. In prokaryotes, biocomputational identification
      of homologs of known ncRNAs in other species often fails due to weakly
      evolutionarily conserved sequences, structures, synteny and genome localization,
      except in the case of evolutionarily closely related species. To eliminate
      results from weak conservation, we focused on RNA structure, which is the most
      conserved ncRNA property. Analysis of the structure of one of the few well
      studied bacterial ncRNAs, 6S RNA, demonstrated that unlike optimal and consensus
      structures, suboptimal structures are capable of capturing RNA homology even in
      divergent bacterial species. A computational procedure for the identification of
      homologous ncRNAs using suboptimal structures was created. The suggested
      procedure was applied to strongly divergent bacterial species and was capable of
      identifying homologous ncRNAs.

PMID- 21193489
TI  - Weekly paclitaxel combining with gemcitabine is an effective and safe treatment
      for advanced breast cancer patients.
AB  - OBJECTIVE: Patients with metastatic breast cancer usually accept several lines of
      chemotherapy. This retrospective study is to analyze the therapeutic effect and
      tolerance of weekly paclitaxel/gemcitabine combination on patients with
      metastatic breast cancer. METHODS: Paclitaxel 80 mg/m(2) and gemcitabine 800
      mg/m(2) were administered sequentially on days 1, 8 and 15 every 28 days.
      Patients with measurable metastatic breast cancer or locally advanced breast
      cancer were included. RESULTS: From March 2005 to December 2006, 50 patients
      received this treatment at Chang Gung Memorial Hospital, Kaohsiung Medical
      Center. Thirteen (26%) patients accepted this regimen as their first-line
      treatment for metastatic breast cancer and 25 (50%) patients accepted this
      regimen after at least three lines of therapies for metastatic breast cancer. The
      overall response rate was 56% (95% confidence interval: 42.2-69.8%), 2 patients
      achieved complete response and 26 patients (52, 95% confidence interval: 38.2
      65.9%) achieved partial response. The median progression free survival was 7.4
      months (95% confidence interval: 5.5-9.3 months), and the median overall survival
      was 19.0 months (95% confidence interval: 9.7-28.3 months). Except alopecia, the
      most common Grade 3/4 toxicities were anemia and leucopenia; the incidences of
      both were fewer than 10%. CONCLUSIONS: The combination of weekly gemcitabine and
      paclitaxel in patients with advanced breast cancer showed acceptable outcome and
      excellent toxic profiles. This therapeutic benefit could be achieved in any
      linage of patients with good performance status; earlier usage of this regimen
      can provide better result.

PMID- 21193490
TI  - Fine-scale analysis of X chromosome inactivation in the male germ line of
      Drosophila melanogaster.
AB  - Inactivation of the X chromosome in the male germ line has been suggested to
      contribute to the excess of gene movement off the X chromosome and the paucity of
      X-linked male-biased genes that have been observed in Drosophila species. Recent
      experimental work has demonstrated the transcriptional inactivation of the X
      chromosome during spermatogenesis, but it is not known if some regions of the X
      escape inactivation. To test this, we analyzed the expression of 112 precisely
      mapped, testis-specific reporter gene insertions along the X chromosome. All of
      the reporter gene insertions showed low levels of expression that were
      significantly less than those of autosomal insertions, suggesting that the X
      chromosome is globally inactivated in the male germ line. There was no evidence
      for regions of the X chromosome escaping inactivation, including cytological
      region 19, which appears to be a hot spot for newly evolved, testis-expressed
      genes.

PMID- 21193491
TI  - Differential item functioning on the Five Facet Mindfulness Questionnaire is
      minimal in demographically matched meditators and nonmeditators.
AB  - A recent study of the Five Facet Mindfulness Questionnaire reported high levels
      of differential item functioning (DIF) for 18 of its 39 items in meditating and
      nonmeditating samples that were not demographically matched. In particular,
      meditators were more likely to endorse positively worded items whereas
      nonmeditators were more likely to deny negatively worded (reverse-scored) items.
      The present study replicated these analyses in demographically matched samples of
      meditators and nonmeditators (n = 115 each) and found that evidence for DIF was
      minimal. There was little or no evidence for differential relationships between
      positively and negatively worded items for meditators and nonmeditators. Findings
      suggest that DIF based on items' scoring direction is not problematic when the
      Five Facet Mindfulness Questionnaire is used to compare demographically similar
      meditators and nonmeditators.

PMID- 21193492
TI  - Examining the construct validity of the elemental psychopathy assessment.
AB  - Lynam and colleagues recently developed a new self-report inventory for the
      assessment of psychopathy, the Elemental Psychopathy Assessment (EPA). Using a
      sample of undergraduates (N = 227), the authors examined the construct validity
      of the EPA by examining its correlations with self and stranger ratings on the
      Five-Factor Model, as well as self-reported ratings of personality disorders,
      social cognition, and love styles. The EPA psychopathy scores manifested expected
      correlations with both self and stranger ratings of the Five-Factor Model,
      particularly with the domains of Agreeableness and Conscientiousness, and were
      significantly related to various forms of personality pathology such as
      narcissism and antisocial personality disorders. The EPA also manifested expected
      relations with aggressive social cognitions. Finally, the EPA psychopathy scores
      were correlated with romantic love styles indicative of game playing and
      infidelity. The current results provide further evidence of the construct
      validity of the EPA as it manifests relations consistent with the nomological
      network of psychopathy.

PMID- 21193493
TI  - The impact of emotional priming on MMPI-2 scale scores.
AB  - The current study investigated potential emotional priming effects on Minnesota
      Multiphasic Personality Inventory-2 (MMPI-2) scale scores. Participants included
      98 college students who completed a personal narrative intended to induce
      temporary mood states, the MMPI-2, and a mood rating inventory. Results of the
      mood manipulation indicated that the individuals who first wrote a negative
      personal narrative reported a less positive mood (d = -.79). However, analysis of
      variance results indicated no statistically significant differences on MMPI-2
      scale scores between groups (median eta(2) = .005). Limitations and future
      directions are discussed.

PMID- 21193494
TI  - Influence of genospecies of Acinetobacter baumannii complex on clinical outcomes
      of patients with acinetobacter bacteremia.
AB  - BACKGROUND: acinetobacter baumannii complex infections are increasing in
      prevalence and are associated with a high mortality. Biochemical classification
      tests cannot differentiate A. baumannii (genospecies 2) from other genospecies.
      Genospecies typing offers a potential tool to determine whether there are major
      differences in pathogenicity among the genospecies. METHODS: adult patients with
      A. baumannii complex bacteremia in intensive care units were prospectively
      observed from January 2007 through July 2009. A. baumannii complex was identified
      by biochemical methods and the Phoenix bacterial identification system.
      Genospecies were identified by 16S-23S ribosomal RNA intergenic-spacer
      sequencing. RESULTS: among the 135 patients with A. baumannii complex bacteremia,
      87 (64.4%) had isolates that belonged to genospecies 2, 36 (26.7%) had isolates
      that belonged to genospecies 13TU, and 12 (8.9%) had isolates that belonged to
      genospecies 3. Patients with A. baumannii (genospecies 2) bacteremia were more
      likely to have pneumonia than were patients with bacteremia due to genospecies
      13TU (63.2 % vs 27.8%; P =.001), whereas patients with bacteremia due to
      genospecies 13TU were more likely to have primary bacteremia (69.4% vs 20.7%; P
      <.001). Genospecies 2 was less susceptible to antibiotics than were other
      genospecies. It was associated with a higher rate of mortality than was
      genospecies 13TU (58.6% vs 16.7%; P < .001). On multivariate analysis,
      genospecies 2 was an independent predictor of mortality (odds ratio, 5.46; 95%
      confidence interval, 2.00-14.91; P = .001). CONCLUSIONS: genospecies 2 of the A.
      baumannii complex was associated with greater resistance to antibiotics and
      higher mortality among bacteremic patients, compared with other genospecies,
      especially genospecies 13TU. These findings emphasize the need to focus on
      genospecies to better understand the pathogenesis and epidemiology of infections
      caused by the A. baumannii complex.

PMID- 21193495
TI  - Discontinuation of long-term benzodiazepine use: 10-year follow-up.
AB  - BACKGROUND: Several interventions aiming at discontinuation of long-term
      benzodiazepine use have been proven effective in the short term. However, data on
      the persistence of discontinuation are lacking. OBJECTIVES: To assess 10-year
      follow-up status in patients who succeeded in stopping benzodiazepine use after a
      discontinuation letter from the patient's own GP. To identify determinants of
      successful discontinuation on the long term. METHODS: Follow-up data of patients
      who participated in a large prospective, controlled stepped care intervention
      programme among long-term benzodiazepine users in primary care. RESULTS: At 10
      year follow-up, the percentage of benzodiazepine abstinence was 58.8%. Non
      abstinent patients used lower doses of benzodiazepine. Being abstinent at 21
      months after the intervention predicted abstinence at 10-year follow-up.
      CONCLUSIONS: Ten years after a minimal intervention to decrease long-term
      benzodiazepine use, the majority of patients who were able to discontinue
      benzodiazepine use initially, does not use benzodiazepines at 10-year follow-up.
      Patients who did not succeed in maintaining abstinence from benzodiazepines
      appear to use lower or average dosages.

PMID- 21193496
TI  - Repeated falls and broken bones.

PMID- 21193497
TI  - Income to survive. How much do BMA and RSM pay their lowest paid workers?

PMID- 21193501
TI  - Return of the postcode lottery.

PMID- 21193503
TI  - Subarachnoid haemorrhage. Beware adopting rigid rules.

PMID- 21193504
TI  - Earlier retirement. Retirement and socioeconomic inequalities.

PMID- 21193505
TI  - Subarachnoid haemorrhage. Clinical gestalt needed.

PMID- 21193506
TI  - Subarachnoid haemorrhage. Cases may have been missed.

PMID- 21193507
TI  - Referrals to secondary care. Referral rates for postmenopausal bleeding are not
      respectable.

PMID- 21193508
TI  - Extracorporeal life support . Is recommended for severe accidental hypothermia.

PMID- 21193509
TI  - Subarachnoid haemorrhage. Reinventing the wheel, square.

PMID- 21193510
TI  - Imaging the dead. Can supplement but not replace autopsy in medicolegal death
      investigation.

PMID- 21193512
TI  - Abortions in Spain fell for the first time in a decade in 2009.

PMID- 21193513
TI  - Insights into sick sinus syndrome from an inducible mouse model.
AB  - AIMS: Sick sinus syndrome is a generalized abnormality of cardiac impulse
      formation and is responsible for a large proportion of pacemaker implantations.
      Although the exact aetiology is not known, it is widely accepted that age
      dependent degenerative fibrosis of nodal tissue is the most common cause. Despite
      its importance, an animal model for sick sinus syndrome is lacking. We attempted
      to generate a mouse model phenocopying the pathohistological changes as well as
      the characteristic arrhythmic manifestations of this syndrome. METHODS AND
      RESULTS: We crossed two genetically engineered mouse lines, ROSA-eGFP-DTA and
      HCN4-KiT-Cre, to achieve an inducible deletion of cells specifically in the
      cardiac pacemaking and conduction system. This deletion resulted in a
      degenerative fibrosis of nodal tissue, which accurately reflects the
      pathohistological findings in human sick sinus syndrome. The extent of the sino
      atrial fibrosis could be controlled by varying the dosage of the inducing
      substance, tamoxifen. A high-dose protocol resulted in the complete ablation of
      all sino-atrial cells as demonstrated by histochemical analysis and quantitative
      reverse transcriptase-polymerase chain reaction. The animals developed a variety
      of arrhythmias, including progressive bradycardia, sinus pauses, supraventricular
      and ventricular tachycardia and chronotropic incompetence. Remarkably, the
      complete destruction of the primary pacemaker centre resulted in only a small
      increase in mortality. CONCLUSION: This study describes the generation and
      analysis of an inducible mouse model which closely reflects the
      pathophysiological characteristics of sick sinus syndrome. The model, with the
      ability to control the extent of nodal cell ablation and fibrosis, offers new
      insights into sick sinus syndrome and other cardiac conduction diseases.

PMID- 21193514
TI  - US medical school faculty still break conflict of interest rules, report says.

PMID- 21193516
TI  - The role of AlkB protein in repair of 1,N6-ethenoadenine in Escherichia coli
      cells.
AB  - Etheno (epsilon) DNA adducts, including 1,N(6)-ethenoadenine (epsilonA), are
      formed by various bifunctional agents of exogenous and endogenous origin. The AT
      >TA transversion, the most frequent mutation provoked by the presence of epsilonA
      in DNA, is very common in critical codons of the TP53 and RAS genes in tumours
      induced by exposure to carcinogenic vinyl compounds. Here, using a method that
      allows examination of the mutagenic potency of a metabolite of vinyl chloride,
      chloroacetaldehyde (CAA), but eliminates its cytotoxicity, we studied the
      participation of alkA, alkB and mug gene products in the repair of epsilonA in
      Escherichia coli cells. The test system used comprised the pIF105 plasmid bearing
      the lactose operon of CC105 origin, which allowed monitoring of Lac(+) revertants
      that arose by AT->TA substitutions due to the modification of adenine by CAA. The
      plasmid was CAA-modified in vitro and replicated in E.coli of various genetic
      backgrounds (wt, alkA, alkB, mug, alkAalkB, alkAmug and alkBmug). To modify the
      levels of the AlkA and AlkB proteins, mutagenesis was studied in E.coli cells
      induced or not in adaptive response to alkylating agents. Considering the levels
      of CAA-induced Lac(+) revertants in strains harbouring the CAA-modified pIF105
      plasmid and induced or not in adaptive response, we conclude that the AlkB
      dioxygenase plays a major role in decreasing the level of AT->TA mutations, thus
      in the repair of epsilonA in E.coli cells. The observed differences of mutation
      frequencies in the various mutant strains assayed indicate that Mug glycosylase
      is also engaged in the repair of epsilonA, whereas the role the AlkA glycosylase
      in this repair is negligible.

PMID- 21193517
TI  - Seasonal variations in the levels of PAH-DNA adducts in young adults living in
      Mexico City.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous components of polluted
      air. The Mexico City Metropolitan Area (MCMA), one of the most densely populated
      areas in the world, is 2240 m above sea level. At this altitude, less oxygen is
      available, making combustion less efficient and therefore producing more PAH
      pollutants. According to the Automatic Monitoring Network in Mexico City (RAMA,
      for its Spanish initials;
      http://www.sma.df.gob.mx/simat2/informaciontecnica/index.php?opcion=5&opciondifus
      on_bd=90), which performs environmental monitoring, the critical air pollutants
      in Mexico City are ozone and particulate matter (PM). PM emissions increase
      during the dry season (winter to spring) and decrease during the rainy season
      (summer to autumn). The bioactivation of some PAHs produces reactive metabolites
      that bind to DNA, and the presence of elevated levels of PAH-DNA adducts in
      tissues such as blood lymphocytes represents an elevated risk for the development
      of cancer. We have compared the levels of PAH-DNA adducts and the percentage of
      cells with chromosomal aberrations (CWAs) using a matched set of peripheral blood
      lymphocytes obtained on two separate occasions from young non-smoking inhabitants
      of the MCMA (n = 92) during the 2006 dry season and the following rainy season.
      PAH-DNA adducts were analysed using the r7, t8-dihydroxy-t-9, 10-oxy-7,8,9,10
      tetrahydrobenzo[a]pyrene (BPDE)-DNA chemiluminescence immunoassay (CIA). The
      percentages of CWA were determined in cultured lymphocytes from the same
      individuals. Both DNA adduct levels and chromosomal aberrations were tested for
      correlation with lifestyle and the polymorphisms of cytochromes P450 CYP1A1 and
      CYP1B1 as well as glutathione-S-transferases GSTM1 and GSTT1. The levels of PAH
      DNA adducts were significantly higher (P < 0.001) in the dry season (10.66 +/-
      3.05 per 10(9) nt, n = 92) than during the rainy season (9.50 +/- 2.85 per 10(9)
      nt, n = 92) and correlated with the seasonal levels of particulate matter with a
      diameter of <= 10 MUm (PM(10)). The percentage of CWA was not seasonally related;
      however, significant associations between the number of risk alleles and adduct
      levels in the dry (R = 0.298, P = 0.048) and in the wet seasons (R = 0.473, P =
      0.001) were observed.

PMID- 21193518
TI  - Detection of genotoxicants in Brassicales using endogenous DNA as a surrogate
      target and adducts determined by 32P-postlabelling as an experimental end point.
AB  - Some plants use electrophilic metabolites as a defence against biological
      enemies. Some of them may react with DNA. We devised a new model to test this
      hypothesis. Plant tissue was homogenised. After incubation of the homogenate at
      37 degrees C for varying periods, the plant DNA was analysed for the presence of
      adducts using the (32)P-postlabelling technique. Adducts were detected with all
      Brassicales studied. Broccoli was investigated in detail. Adducts were absent in
      DNA isolated immediately after homogenisation of the plant. Subsequently, five
      characteristic adduct spots were formed in the homogenate, the maximum being
      reached after nearly 4 h. Adduct formation was low when broccoli was steamed
      before homogenisation, but was re-established when myrosinase was added to the
      homogenate, indicating that the active constituents were glucosinolates. Broccoli
      juice was mutagenic to Salmonella typhimurium, forming the same adduct spots in
      these target cells as in plant homogenate, but the relative intensity of the
      individual spots varied between both models. The patterns of adduct spots formed
      in homogenates of 15 other Brassicales species and tissues were similar to those
      detected with broccoli florets heads. However, the relative intensities of the
      spots varied. Sporadically, some spots were missing or additional spots appeared.
      These results, therefore, suggest that several different glucosinolates
      contribute to the adduct formation.

PMID- 21193519
TI  - Maternal communication style, problem-solving and dietary adherence in young
      children with type 1 diabetes.
AB  - The incidence of type 1 diabetes (T1D) in young children is increasing markedly
      however young children have been overlooked in paediatric adherence research
      despite the unique challenges their care presents. We investigated the relation
      between maternal communication style and adherence to the dietary regimen in 40
      children with T1D, aged 2-8 years, and their mothers. Mothers completed measures
      of children's sugar consumption, parent-child communication quality, and child
      psychological functioning. Mothers and children engaged in a videotaped problem
      solving task related to the dietary regimen, with maternal utterances analysed
      for behavioural control style (e.g., commands versus suggestions) and cognitive
      complexity (e.g., provision of labels versus questions). Maternal communications
      which engaged children, behaviourally and cognitively, in the task were
      associated with better adherence, medical, communication quality, and child
      adjustment outcomes. We conclude that adherence and health (medical and
      psychological) are optimized when young children are given opportunities to
      participate in their care.

PMID- 21193520
TI  - Discovering approximate-associated sequence patterns for protein-DNA
      interactions.
AB  - MOTIVATION: The bindings between transcription factors (TFs) and transcription
      factor binding sites (TFBSs) are fundamental protein-DNA interactions in
      transcriptional regulation. Extensive efforts have been made to better understand
      the protein-DNA interactions. Recent mining on exact TF-TFBS-associated sequence
      patterns (rules) has shown great potentials and achieved very promising results.
      However, exact rules cannot handle variations in real data, resulting in limited
      informative rules. In this article, we generalize the exact rules to approximate
      ones for both TFs and TFBSs, which are essential for biological variations.
      RESULTS: A progressive approach is proposed to address the approximation to
      alleviate the computational requirements. Firstly, similar TFBSs are grouped from
      the available TF-TFBS data (TRANSFAC database). Secondly, approximate and highly
      conserved binding cores are discovered from TF sequences corresponding to each
      TFBS group. A customized algorithm is developed for the specific objective. We
      discover the approximate TF-TFBS rules by associating the grouped TFBS
      consensuses and TF cores. The rules discovered are evaluated by matching
      (verifying with) the actual protein-DNA binding pairs from Protein Data Bank
      (PDB) 3D structures. The approximate results exhibit many more verified rules and
      up to 300% better verification ratios than the exact ones. The customized
      algorithm achieves over 73% better verification ratios than traditional methods.
      Approximate rules (64-79%) are shown statistically significant. Detailed
      variation analysis and conservation verification on NCBI records demonstrate that
      the approximate rules reveal both the flexible and specific protein-DNA
      interactions accurately. The approximate TF-TFBS rules discovered show great
      generalized capability of exploring more informative binding rules.

PMID- 21193521
TI  - Multilign: an algorithm to predict secondary structures conserved in multiple RNA
      sequences.
AB  - MOTIVATION: With recent advances in sequencing, structural and functional studies
      of RNA lag behind the discovery of sequences. Computational analysis of RNA is
      increasingly important to reveal structure-function relationships with low cost
      and speed. The purpose of this study is to use multiple homologous sequences to
      infer a conserved RNA structure. RESULTS: A new algorithm, called Multilign, is
      presented to find the lowest free energy RNA secondary structure common to
      multiple sequences. Multilign is based on Dynalign, which is a program that
      simultaneously aligns and folds two sequences to find the lowest free energy
      conserved structure. For Multilign, Dynalign is used to progressively construct a
      conserved structure from multiple pairwise calculations, with one sequence used
      in all pairwise calculations. A base pair is predicted only if it is contained in
      the set of low free energy structures predicted by all Dynalign calculations. In
      this way, Multilign improves prediction accuracy by keeping the genuine base
      pairs and excluding competing false base pairs. Multilign has computational
      complexity that scales linearly in the number of sequences. Multilign was tested
      on extensive datasets of sequences with known structure and its prediction
      accuracy is among the best of available algorithms. Multilign can run on long
      sequences (> 1500 nt) and an arbitrarily large number of sequences. AVAILABILITY:
      The algorithm is implemented in ANSI C++ and can be downloaded as part of the
      RNAstructure package at: http://rna.urmc.rochester.edu.

PMID- 21193522
TI  - Principal network analysis: identification of subnetworks representing major
      dynamics using gene expression data.
AB  - MOTIVATION: Systems biology attempts to describe complex systems behaviors in
      terms of dynamic operations of biological networks. However, there is lack of
      tools that can effectively decode complex network dynamics over multiple
      conditions. RESULTS: We present principal network analysis (PNA) that can
      automatically capture major dynamic activation patterns over multiple conditions
      and then generate protein and metabolic subnetworks for the captured patterns. We
      first demonstrated the utility of this method by applying it to a synthetic
      dataset. The results showed that PNA correctly captured the subnetworks
      representing dynamics in the data. We further applied PNA to two time-course gene
      expression profiles collected from (i) MCF7 cells after treatments of HRG at
      multiple doses and (ii) brain samples of four strains of mice infected with two
      prion strains. The resulting subnetworks and their interactions revealed network
      dynamics associated with HRG dose-dependent regulation of cell proliferation and
      differentiation and early PrPSc accumulation during prion infection.
      AVAILABILITY: The web-based software is available at:
      http://sbm.postech.ac.kr/pna.

PMID- 21193523
TI  - Cancer therapy design based on pathway logic.
AB  - MOTIVATION: Cancer encompasses various diseases associated with loss of cell
      cycle control, leading to uncontrolled cell proliferation and/or reduced
      apoptosis. Cancer is usually caused by malfunction(s) in the cellular signaling
      pathways. Malfunctions occur in different ways and at different locations in a
      pathway. Consequently, therapy design should first identify the location and type
      of malfunction to arrive at a suitable drug combination. RESULTS: We consider the
      growth factor (GF) signaling pathways, widely studied in the context of cancer.
      Interactions between different pathway components are modeled using Boolean logic
      gates. All possible single malfunctions in the resulting circuit are enumerated
      and responses of the different malfunctioning circuits to a 'test' input are used
      to group the malfunctions into classes. Effects of different drugs, targeting
      different parts of the Boolean circuit, are taken into account in deciding drug
      efficacy, thereby mapping each malfunction to an appropriate set of drugs.

PMID- 21193524
TI  - Modulation of visceral hypersensitivity by glial cell line-derived neurotrophic
      factor family receptor &alpha;-3 in colorectal afferents.
AB  - Irritable bowel syndrome is characterized by colorectal hypersensitivity and
      contributed to by sensitized mechanosensitive primary afferents and recruitment
      of mechanoinsensitive (silent) afferents. Neurotrophic factors are well known to
      orchestrate dynamic changes in the properties of sensory neurons. Although pain
      modulation by proteins in the glial cell line-derived neurotrophic factor (GDNF)
      family has been documented in various pathophysiological states, their role in
      colorectal hypersensitivity remains unexplored. Therefore, we investigated the
      involvement of the GDNF family receptor alpha-3 (GFRalpha3) signaling in visceral
      hypersensitivity by quantifying visceromotor responses (VMR) to colorectal
      distension before and after intracolonic treatment with 2,4,6-trinitrobenzene
      sulfonic acid (TNBS). Baseline responses to colorectal distension did not differ
      between C57BL/6 and GFRalpha3 knockout (KO) mice. Relative to intracolonic saline
      treatment, TNBS significantly enhanced the VMR to colorectal distension in
      C57BL/6 mice 2, 7, 10, and 14 days posttreatment, whereas TNBS-induced visceral
      hypersensitivity was significantly suppressed in GFRalpha3 KO mice. The
      proportion of GFRalpha3 immunopositive thoracolumbar and lumbosacral colorectal
      dorsal root ganglion neurons was significantly elevated 2 days after TNBS
      treatment. In single fiber recordings, responses to circumferential stretch of
      colorectal afferent endings in C57BL/6 mice were significantly increased
      (sensitized) after exposure to an inflammatory soup, whereas responses to stretch
      did not sensitize in GFRalpha3 KO mice. These findings suggest that enhanced
      GFRalpha3 signaling in visceral afferents may contribute to development of
      colorectal hypersensitivity.

PMID- 21193526
TI  - Treatment with IL-27 attenuates experimental colitis through the suppression of
      the development of IL-17-producing T helper cells.
AB  - Inflammatory bowel disease (IBD) represents a group of chronic inflammatory
      diseases characterized by inflammation and relapsing gastrointestinal disorders.
      Recent studies have shown that Th17 cells, which are well known as key mediators
      of chronic inflammation, have a pivotal role in onset and development of IBD in
      humans and mice, alike. In recent years, it has been reported that IL-27, which
      is an IL-12-related heterodimeric cytokine consisting of EBI3 and p28 subunits,
      act directly on naive T cells to suppress the differentiation of Th17 cells.
      However, effects of exogenous IL-27 on the IBD are not well elucidated. To
      clarify the suppressive effect of IL-27 treatment on IBD, we applied the flexible
      linking method to EBI3 and p28 subunits and generated a single-chain human IL-27
      (scIL-27). scIL-27 inhibited xenogenic mouse Th17 cell differentiation in vitro,
      indicating that scIL-27 also acts in mouse immune systems. In a 2,4,6
      trinitrobenzene sulfonic acid (TNBS)-induced mouse acute colitis model,
      subcutaneous scIL-27 treatment significantly improved the colon length, extent of
      necrosis, and ulceration and thickened epithelium and several pathological scores
      in a dose-dependent manner. scIL-27 clearly suppressed several inflammatory
      cytokines, including IL-17, in inflamed colon, except for anti-inflammatory
      cytokine IL-10. The mesenteric lymph node cells from scIL-27-treated mice also
      exhibited a reduced inflammatory response and, furthermore, a lower population of
      Th17 cells than those of PBS-treated mice. Finally, we showed the therapeutic
      efficacy of scIL-27 on TNBS-induced colitis even after active colitis was
      established. These results suggest new possible therapeutic approaches for IBD,
      including disorders such as Crohn's disease and ulcerative colitis.

PMID- 21193525
TI  - Gastrin stimulates expression of plasminogen activator inhibitor-1 in gastric
      epithelial cells.
AB  - Plasminogen activator inhibitor (PAI)-1 is associated with cancer progression,
      fibrosis and thrombosis. It is expressed in the stomach but the mechanisms
      controlling its expression there, and its biological role, are uncertain. We
      sought to define the role of gastrin in regulating PAI-1 expression and to
      determine the relevance for gastrin-stimulated cell migration and invasion. In
      gastric biopsies from subjects with elevated plasma gastrin, the abundances of
      PAI-1, urokinase plasminogen activator (uPA), and uPA receptor (uPAR) mRNAs
      measured by quantitative PCR were increased compared with subjects with plasma
      concentrations in the reference range. In patients with hypergastrinemia due to
      autoimmune chronic atrophic gastritis, there was increased abundance of PAI-1,
      uPA, and uPAR mRNAs that was reduced by octreotide or antrectomy.
      Immunohistochemistry revealed localization of PAI-1 to parietal cells and
      enterochromaffin-like cells in micronodular neuroendocrine tumors in
      hypergastrinemic subjects. Transcriptional mechanisms were studied by using a PAI
      1-luciferase promoter-reporter construct transfected into AGS-G(R) cells. There
      was time- and concentration-dependent increase of PAI-1-luciferase expression in
      response to gastrin that was reversed by inhibitors of the PKC and MAPK pathways.
      In Boyden chamber assays, recombinant PAI-1 inhibited gastrin-stimulated AGS-G(R)
      cell migration and invasion, and small interfering RNA treatment increased
      responses to gastrin. We conclude that elevated plasma gastrin concentrations are
      associated with increased expression of gastric PAI-1, which may act to restrain
      gastrin-stimulated cell migration and invasion.

PMID- 21193527
TI  - Cytokeratin 18 is a specific marker of bovine intestinal M cell.
AB  - Microfold (M) cells in the follicle-associated epithelium (FAE) of Peyer's
      patches have an important role in mucosal immune responses. A primary difficulty
      for investigations of bovine M cells is the lack of a specific molecular marker.
      To identify such a marker, we investigated the expression of several kinds of
      intermediate filament proteins using calf Peyer's patches. The expression
      patterns of cytokeratin (CK) 18 in jejunal and ileal FAE were very similar to the
      localization pattern of M cells recognized by scanning electron microscopy.
      Mirror sections revealed that jejunal CK18-positive cells had irregular and
      sparse microvilli, as well as pocket-like structures containing lymphocytes,
      typical morphological characteristic of M cells. However, CK18-negative cells had
      regular and dense microvilli on their surface, typical of the morphology of
      enterocytes. In contrast, CK20 immunoreactivity was detected in almost all
      villous epithelial cells and CK18-negative cells in the FAE. CK18-positive
      proliferating transit-amplifying cells in the crypt exchanged CK18 for CK20 above
      the mouth of the crypt and after moving to the villi; however, CK18-positive M
      cells in the crypt continued their expression of CK18 during movement to the FAE
      region. Terminal deoxynucleotidyl-transferase-mediated deoxyuridine-triphosphate
      biotin nick-end labeling-positive apoptotic cells were specifically detected at
      the apical region of villi and FAE in the jejunum and ileum, and all were also
      stained for CK20. These data indicate that CK18 may be a molecular marker for
      bovine M cells in FAE and that M cells may transdifferentiate to CK20-positive
      enterocytes and die by apoptosis in the apex of the FAE.

PMID- 21193528
TI  - Temporal relationships between wall motion, intraluminal pressure, and flow in
      the isolated rabbit small intestine.
AB  - Intraluminal manometry is a tool commonly used to record motility in the human
      digestive tract. The recorded signal results from a combination of factors,
      including the hydrodynamic pressure transmitted through the intestinal contents
      due to contraction of the gut wall and the force of the gut wall acting on the
      sensors in regions of a luminal occlusion. However, the actual relationships
      between small bowel wall contraction, the measured intraluminal pressure, and the
      resultant flow have not been directly addressed. Video recording and high
      resolution fiber-optic manometry were used to create spatiotemporal video maps of
      diameter and intraluminal pressure from isolated segments of rabbit small
      intestine. In the unstimulated gut, longitudinal muscle contractions were the
      only detectable motor pattern; circular muscle contractions were elicited by
      distension or erythromycin (1 MUM). Longitudinal muscle contractions were not
      lumen-occlusive, although they caused measurable low-amplitude changes in
      pressure. Localized nonpropagating circular muscle contractions caused small
      localized, nonpropagating peaks of intraluminal pressure. Propagating
      contractions of circular muscle evoked larger, propagating pressure changes that
      were associated with outflow. Propagating circular muscle contractions often
      caused dilation of aboral receiving segments, corresponding to "common cavities";
      these were propulsive, despite their low intraluminal pressure. The highest
      amplitude pressure events were caused by lumen-occlusive circular muscle
      contractions that squeezed directly against the catheter. These data allow us to
      define the complex relationships between wall motion, intraluminal pressure, and
      flow. A strong correlation between circular and longitudinal muscle contraction
      and intraluminal pressure was demonstrated. Common-cavity pressure events, caused
      by propulsion of content by circular muscle contractions into a receptive
      segment, were often of low amplitude but were highly propulsive. Studies of wall
      motion in isolated preparations, combined with manometry, can assist in
      interpretation of pressure recordings in vivo.

PMID- 21193529
TI  - Interrelationships between tissue iron status and erythropoiesis during
      postweaning development following neonatal iron deficiency in rats.
AB  - Dietary iron is particularly critical during periods of rapid growth such as in
      neonatal development. Human and rodent studies have indicated that iron
      deficiency or excess during this critical stage of development can have
      significant long- and short-term consequences. Since the requirement for iron
      changes during development, the availability of adequate iron is critical for the
      differentiation and maturation of individual organs participating in iron
      homeostasis. We have examined in rats the effects of dietary iron supplement
      following neonatal iron deficiency on tissue iron status in relation to
      erythropoietic ability during 16 wk of postweaning development. This
      physiological model indicates that postweaning iron-adequate diet following
      neonatal iron deficiency adversely affects erythroid differentiation in the bone
      marrow and promotes splenic erythropoiesis leading to splenomegaly and
      erythrocytosis. This altered physiology of iron homeostasis during postweaning
      development is also reflected in the inability to maintain liver and spleen iron
      concentrations and the altered expression of iron regulatory proteins in the
      liver. These studies provide critical insights into the consequences of neonatal
      iron deficiency and the dietary iron-induced cellular signals affecting iron
      homeostasis during early development.

PMID- 21193530
TI  - Inhibition of gastric motility by hyperglycemia is mediated by nodose ganglia
      KATP channels.
AB  - The inhibitory action of hyperglycemia is mediated by vagal afferent fibers
      innervating the stomach and duodenum. Our in vitro studies showed that a subset
      of nodose ganglia neurons is excited by rising ambient glucose, involving
      inactivation of ATP-sensitive K(+) (K(ATP)) channels and leading to membrane
      depolarization and neuronal firing. To investigate whether nodose ganglia K(ATP)
      channels mediate gastric relaxation induced by hyperglycemia, we performed in
      vivo gastric motility studies to examine the effects of K(ATP) channel activators
      and inactivators. Intravenous infusion of 20% dextrose induced gastric relaxation
      in a dose-dependent manner. This inhibitory effect of hyperglycemia was blocked
      by diazoxide, a K(ATP) channel activator. Conversely, tolbutamide, a K(ATP)
      channel inactivator, induced dose-dependent gastric relaxation, an effect similar
      to hyperglycemia. Vagotomy, perivagal capsaicin treatment, and hexamethonium each
      prevented the inhibitory action of tolbutamide. Similarly, N(G)-nitro-l-arginine
      methyl ester, an inhibitor of nitric oxide synthase, also blocked tolbutamide's
      inhibitory effect. To show that K(ATP) channel inactivation at the level of the
      nodose ganglia induces gastric relaxation, we performed electroporation of the
      nodose ganglia with small interfering RNA of Kir6.2 (a subunit of K(ATP)) and
      plasmid pEGFP-N1 carrying the green fluorescent protein gene. The gastric
      responses to hyperglycemia and tolbutamide were not observed in rats with Kir6.2
      small interfering RNA-treated nodose ganglia. However, these rats responded to
      secretin, which acts via the vagal afferent pathway, independently of K(ATP)
      channels. These studies provide in vivo evidence that hyperglycemia induces
      gastric relaxation via the vagal afferent pathway. This action is mediated
      through inactivation of nodose ganglia K(ATP) channels.

PMID- 21193531
TI  - Cooling of cilia allows functional analysis of the beat pattern for diagnostic
      testing.
AB  - BACKGROUND: Reports of the effect of low temperatures on ciliary beat frequency
      (CBF) are conflicting, and the effect on ciliary beat pattern has not been
      reported. We aimed to clarify this association and determine whether cooling of
      cilia may allow ciliary function to be assessed without the need of expensive
      high-speed video microscopy. METHODS: Fourteen nasal brush biopsy samples were
      collected, and the CBF and beat pattern of undisrupted ciliated edges were
      evaluated. Two methods were used to strictly control changes in temperature: One
      enabled rapid transitory measurements during cooling and warming, and the other
      was used to maintain accurate low temperatures over longer periods of time.
      RESULTS: A sigmoid relationship between CBF and temperature was observed. CBF
      decreased with cooling and increased with warming. Ciliary function was
      unaffected by the direction of temperature change and was maintained down to 2
      degrees C. The percentage of dyskinetic cilia observed at 2 degrees C or 4
      degrees C was unchanged from that at 37 degrees C. CONCLUSIONS: Contrary to
      previous research, our data show that cilia continue to beat with a normal
      pattern at temperatures as low as 2 degrees C. Slowing of cilia by cooling may
      allow detailed analysis of ciliary beat pattern without the need of expensive
      high-speed video microscopy.

PMID- 21193532
TI  - Impact of a clinical decision support system in an electronic health record to
      enhance detection of alpha1-antitrypsin deficiency.
AB  - BACKGROUND: Because alpha(1)-antitrypsin deficiency (AATD) is underrecognized,
      strategies to enhance guideline-based diagnostic testing are warranted. METHODS:
      We studied the impact of issuing a guideline-based alert within an electronic
      health record (EHR) to test for AATD on the rate of testing for and detection of
      AATD. For patients at the Cleveland Clinic whose physician-ordered pulmonary
      function test results showed airflow obstruction, the rates of testing for and
      detection of AATD were determined during a baseline (prealert) period and again
      after implementing the alert. RESULTS: During the baseline period, among 979
      eligible subjects, 4.7% were tested; 8.9% of those who had phenotype testing
      performed were found to have AATD (serum levels < 100 mg/dL), of whom 3.2% had
      the PI*ZZ genotype. After the alert, among the 624 eligible subjects, the rate of
      testing increased severalfold (15.1%, P < .001), though neither the rate of
      detecting AATD (5.3%) nor PI*ZZ (2.6%) differed from the rates during the
      baseline period. Having an alternate diagnosis (other than asthma) that could
      explain airflow obstruction (eg, congestive heart failure, sarcoidosis,
      Langerhans cell histiocytosis) was associated with a lower rate of testing (P =
      .041), while carrying a diagnosis of asthma tended to increase the testing
      frequency (P = .15). Multivariate analysis showed that younger age and a smoking
      history were associated with being tested. CONCLUSIONS: Issuing an alert within
      an EHR was associated with a severalfold increase in the frequency of testing for
      alpha(1)-antitrypsin without a higher rate of diagnosing severe AATD. While the
      lack of more frequent diagnosis of AATD may reflect a high rate of baseline
      detection, these results prompt consideration of additional strategies to enhance
      detection of AATD.

PMID- 21193533
TI  - Flexible pressure delivery modification of continuous positive airway pressure
      for obstructive sleep apnea does not improve compliance with therapy: systematic
      review and meta-analysis.
AB  - BACKGROUND: Continuous positive airway pressure (CPAP) is the first-line therapy
      for obstructive sleep apnea (OSA), but patient compliance is a major barrier to
      long-term effectiveness. Flexible pressure delivery of PAP reduces pressure
      during early exhalation with the aim of improving comfort and, therefore,
      compliance, leading to subsequent symptoms improvement. METHODS: We undertook a
      systematic literature search of PubMed (January 1, 2000, to July 11, 2010) to
      identify all randomized trials comparing flexible and standard CPAP in adult
      patients with OSA with at least 1-week follow-up. Either we or the original trial
      investigators extracted means, SEs, and sample sizes for all relevant outcome
      measures. We then performed meta-analyses quantifying improvements in objective
      compliance and symptoms as measured by the Epworth Sleepiness Scale (ESS), the
      Maintenance of Wakefulness Test (MWT), and the Psychomotor Vigilance Task (PVT).
      RESULTS: We found 10 relevant trials (599 patients). Meta-analysis of the seven
      trials where we could extract compliance data (514 patients) indicated that
      flexible pressure did not improve compliance compared with CPAP in either the
      parallel (0.16 h; 95% CI, -0.09-0.42; P = .21) or the crossover trials (0.20 h;
      95% CI, -0.26-0.66; P = .39). Flexible pressure caused no improvement over CPAP
      in any secondary outcome (ESS, MWT, PVT, and residual OSA, all P > .05).
      CONCLUSIONS: Flexible pressure modification neither significantly improves
      compliance with CPAP in patients with OSA nor significantly improves patient
      outcomes beyond the effects of CPAP. Unfortunately, we were unable to locate
      compliance data in the correct format for three out of the 10 suitable trials.

PMID- 21193534
TI  - Sleep disturbances and cause-specific mortality: Results from the GAZEL cohort
      study.
AB  - Poor sleep is an increasing problem in modern society, but most previous studies
      on the association between sleep and mortality rates have addressed only
      duration, not quality, of sleep. The authors prospectively examined the effects
      of sleep disturbances on mortality rates and on important risk factors for
      mortality, such as body mass index, hypertension, and diabetes. A total of 16,989
      participants in the GAZEL cohort study were asked validated questions on sleep
      disturbances in 1990 and were followed up until 2009, with <1% loss to follow-up.
      Body mass index, hypertension, and diabetes were measured annually through self
      reporting. During follow-up, a total of 1,045 men and women died. Sleep
      disturbances were associated with a higher overall mortality risk in men (P =
      0.005) but not in women (P = 0.33). This effect was most pronounced for men <45
      years of age (>=3 symptoms vs. none: hazard ratio = 2.03, 95% confidence
      interval: 1.24, 3.33). There were no clear associations between sleep
      disturbances and cardiovascular mortality rates, although men and women with
      sleep disturbances were more likely to develop hypertension and diabetes (P <
      0.001). Compared with people with no sleep disturbances, men who reported >=3
      types of sleep disturbance had an almost 5 times' higher risk of committing
      suicide (hazard ratio = 4.99, 95% confidence interval: 1.59, 15.7). Future
      strategies to prevent premature deaths may benefit from assessment of sleep
      disturbances, especially in younger individuals.

PMID- 21193535
TI  - Multistate analysis of interval-censored longitudinal data: application to a
      cohort study on performance status among patients diagnosed with cancer.
AB  - In observational studies on cancer patients, progression of performance status
      over time can be described by using a multistate model in which state-to-state
      transitions represent changes in a patient's health condition. Although a patient
      experiences transitions in continuous time, assessments on the patient are often
      made at irregularly spaced time points. In this paper, the authors formulate a
      Markov 4-state model for examining longitudinal data on performance status
      collected under intermittent observation. The cohort consisted of 11,342 patients
      diagnosed with cancer in Ontario, Canada, from 2007 to 2009. The authors extend
      the model to estimate the predicted probability of reaching the absorbing state,
      death, over various time intervals. The authors also illustrate what happens to
      the estimated transition intensities if the true observational scheme is
      overlooked. Methods for multistate analysis should be used by epidemiologists,
      since they prove particularly useful for examining the complexities of disease
      processes.

PMID- 21193536
TI  - Profiling Cys34 adducts of human serum albumin by fixed-step selected reaction
      monitoring.
AB  - A method is described for profiling putative adducts (or other unknown covalent
      modifications) at the Cys34 locus of human serum albumin (HSA), which represents
      the preferred reaction site for small electrophilic species in human serum. By
      comparing profiles of putative HSA-Cys34 adducts across populations of interest
      it is theoretically possible to explore environmental causes of degenerative
      diseases and cancer caused by both exogenous and endogenous chemicals. We report
      a novel application of selected-reaction-monitoring (SRM) mass spectrometry,
      termed fixed-step SRM (FS-SRM), that allows detection of essentially all HSA
      Cys34 modifications over a specified range of mass increases (added masses).
      After tryptic digestion, HSA-Cys34 adducts are contained in the third largest
      peptide (T3), which contains 21 amino acids and an average mass of 2433.87 Da.
      The FS-SRM method does not require that exact masses of T3 adducts be known in
      advance but rather uses a theoretical list of T3-adduct m/z values separated by a
      fixed increment of 1.5. In terms of added masses, each triply charged parent ion
      represents a bin of +/-2.3 Da between 9.1 Da and 351.1 Da. Synthetic T3 adducts
      were used to optimize FS-SRM and to establish screening rules based upon selected
      b- and y-series fragment ions. An isotopically labeled T3 adduct is added to
      protein digests to facilitate quantification of putative adducts. We used FS-SRM
      to generate putative adduct profiles from six archived specimens of HSA that had
      been pooled by gender, race, and smoking status. An average of 66 putative adduct
      hits (out of a possible 77) were detected in these samples. Putative adducts
      covered a wide range of concentrations, were most abundant in the mass range
      below 100 Da, and were more abundant in smokers than in nonsmokers. With minor
      modifications, the FS-SRM methodology can be applied to other nucleophilic sites
      and proteins.

PMID- 21193538
TI  - Technology development: an overview.

PMID- 21193537
TI  - Predicting cytotoxic T-cell age from multivariate analysis of static and dynamic
      biomarkers.
AB  - Adoptive T-cell transfer therapy relies upon in vitro expansion of autologous
      cytotoxic T cells that are capable of tumor recognition. The success of this cell
      based therapy depends on the specificity and responsiveness of the T cell clones
      before transfer. During ex vivo expansion, CD8+ T cells present signs of
      replicative senescence and loss of function. The transfer of nonresponsive
      senescent T cells is a major bottleneck for the success of adoptive T-cell
      transfer therapy. Quantitative methods for assessing cellular age and
      responsiveness will facilitate the development of appropriate cell expansion and
      selection protocols. Although several biomarkers of lymphocyte senescence have
      been identified, these proteins in isolation are not sufficient to determine the
      age-dependent responsiveness of T cells. We have developed a multivariate model
      capable of extracting combinations of markers that are the most informative to
      predict cellular age. To acquire signaling information with high temporal
      resolution, we designed a microfluidic chip enabling parallel lysis and fixation
      of stimulated cell samples on-chip. The acquisition of 25 static biomarkers and
      48 dynamic signaling measurements at different days in culture, integrating
      single-cell and population based information, allowed the multivariate regression
      model to accurately predict CD8+ T-cell age. From surface marker expression and
      early phosphorylation events following T-cell receptor stimulation, the model
      successfully predicts days in culture and number of population doublings with
      R2=0.91 and 0.98, respectively. Furthermore, we found that impairment of early
      signaling events following T cell receptor stimulation because of long term
      culture allows prediction of costimulatory molecules CD28 and CD27 expression
      levels and the number of population divisions in culture from a limited subset of
      signaling proteins. The multivariate analysis highlights the information content
      of both averaged biomarker values and heterogeneity metrics for prediction of
      cellular age within a T cell population.

PMID- 21193539
TI  - Primary prevention of sudden cardiac death in silent cardiac sarcoidosis: role of
      programmed ventricular stimulation.
AB  - BACKGROUND: Cardiac involvement in sarcoidosis is often silent and may lead to
      sudden death. This study was designed to assess the value of programmed electric
      stimulation of the ventricle (PES) for risk stratification in patients with
      sarcoidosis and evidence of preclinical cardiac involvement on imaging studies.
      METHODS AND RESULTS: Patients with biopsy-proven systemic sarcoidosis but without
      cardiac symptoms who had evidence of cardiac sarcoidosis on positron emission
      tomography (PET) or cardiac MRI (CMR) were included. All patients underwent
      baseline evaluation, echocardiographic assessment of left ventricular function,
      and programmed electric stimulation of the ventricle. Patients were followed for
      survival and arrhythmic events. Seventy-six patients underwent PES of the
      ventricle. Eight (11%) were inducible for sustained ventricular arrhythmias and
      received an implantable defibrillator. None of the noninducible patients received
      a defibrillator. Left ventricular ejection fraction was lower in patients with
      inducible ventricular arrhythmia (36.4+/-4.2% versus 55.8+/-1.5%, P<0.05). Over a
      median follow-up of 5 years, 6 of 8 patients in the group with inducible
      ventricular arrhythmias had ventricular arrhythmia or died, compared with 1 death
      in the negative group (P<0.0001). CONCLUSIONS: In patients with biopsy-proven
      sarcoidosis and evidence of cardiac involvement on PET or CMR alone, positive PES
      may help to identify patients at risk for ventricular arrhythmia. More
      importantly, patients in this cohort with a negative PES appear to have a benign
      course within the first several years following diagnosis. PES may help to guide
      the use of implantable cardioverter defibrillators in this population.

PMID- 21193541
TI  - Performance of (18)fluorodeoxyglucose-positron emission tomography and
      somatostatin receptor scintigraphy for high Ki67 (>=10%) well-differentiated
      endocrine carcinoma staging.
AB  - OBJECTIVE: The purpose of this prospective study was to compare the performance
      of (111)In-octreotide somatostatin receptor scintigraphy (SRS) and
      (18)fluorodesoxyglucose positron emission tomography (FDG-PET) in aggressive well
      differentiated endocrine carcinoma (WDEC) defined by a high Ki67 (>=10%).
      METHODS: Eighteen consecutive patients explored in a single hospital between
      November 2003 and 2008 for high Ki67 (>=10%) WDEC were prospectively included.
      WDEC were sporadic in 17 cases and secreting in 16 cases. FDG-PET, SRS, and
      computed tomography (CT) were performed within a maximum of 3 months and reviewed
      by two independent readers. For each patient, an analysis per organ and lesion
      was performed. Both the results of conventional imaging and the highest number of
      metastatic organs and distinct lesions visualized by all imaging methods
      including SRS, FDG-PET, and thoraco-abdomino-pelvic CT were considered for the
      determination of the standard. Correlation between tumor slope and maximum
      standardized uptake value, Ki67 value, and grade of uptake at SRS was evaluated.
      RESULTS: FDG-PET, SRS, and CT showed at least one lesion in 18 (100%), 15 (83%),
      and 17 (94%) patients, respectively. A total of 254 lesions were diagnosed in 59
      organs. FDG-PET, SRS, and CT detected 195 (77%), 109 (43%), and 195 (77%) lesions
      in 53 (90%), 30 (51%), and 39 (66%) organs, respectively. FDG-PET, compared to
      SRS, detected more, the same as, and less lesions in 14 (78%), one (6%), and
      three (17%) patients, respectively. A statistical trend was found between Ki67
      value and tumor slope (P = 0.07). Median survival after diagnosis was 25 months
      (range, 6-71 months). CONCLUSION: These results suggest that FDG-PET is more
      sensitive than the SRS for high Ki67 WDEC staging.

PMID- 21193542
TI  - Mortality and morbidity in Cushing's disease over 50 years in Stoke-on-Trent, UK:
      audit and meta-analysis of literature.
AB  - CONTEXT: Pituitary ACTH-dependent Cushing's disease (CD) is uncommon, and there
      are very limited data on long-term mortality. OBJECTIVE: The aim was to summarize
      what is known about mortality in ACTH-dependent CD, to report on our own data,
      and to provide a meta-analysis of six other reports that addressed mortality of
      CD. DESIGN AND METHODS: Vital status of 60 CD patients was recorded as of
      December 31, 2009, and the standardized mortality ratio (SMR) was calculated and
      compared with the general population of England and Wales, United Kingdom. A meta
      analysis of SMRs from seven studies (including ours) was performed for overall
      mortality in CD. Where reported (four studies), a similar meta-analysis was
      performed for those patients whose hypercortisolism was in remission after
      treatment compared to those patients from the same center with persistent
      disease. RESULTS: 1. From Stoke-on-Trent, 51 of 60 patients were female, median
      age at diagnosis was in the range of 36-46 yr, and median follow-up was 15 yr.
      There were 13 deaths, nine due to cardiovascular disease. Overall SMR for the
      whole cohort was 4.8 (95% confidence interval, 2.8-8.3) (P < 0001). SMR for
      vascular disease was 13.8 (7.2-36.5) (P < 0001). For persistent disease (n = 6),
      SMR was 16 (6.7-38.4) vs. remission (n = 54) SMR of 3.3 (1.7-6.7); after
      adjustment for age and sex, relative risk of death for persistent disease was
      10.7 (2.3-48.6) (P = 0.002). Hypertension and diabetes mellitus were associated
      with significantly worse survival. 2. Using a random effects model meta-analysis
      revealed an overall (remission plus persistent disease) SMR of 2.2 (1.45-3.41) (P
      < 0.001). Pooled SMR was 1.2 (0.45-3.2) (P = not significant) for patients in
      remission and 5.5 (2.7-11.3) (P = 0.001) for patients with persistent disease.
      Persistence of disease, older age at diagnosis, and presence of hypertension and
      diabetes are the main determinants of mortality. CONCLUSIONS: Overall mortality
      in CD is double that of the general population. However, patients with CD in
      remission fare much better than those with persistence of hypercortisolism, and
      they appear not to have an increased mortality rate. Hypertension and diabetes
      mellitus are risk factors for worse outcome. Because diagnosis and treatment of
      patients are at a young age, much longer follow-up of patients in remission is
      required before one can be confident that their mortality outcome is no different
      from that of the general population, especially because cardiovascular risk
      factors may persist after successful biochemical control of the disease.

PMID- 21193540
TI  - Exposure to room light before bedtime suppresses melatonin onset and shortens
      melatonin duration in humans.
AB  - CONTEXT: Millions of individuals habitually expose themselves to room light in
      the hours before bedtime, yet the effects of this behavior on melatonin signaling
      are not well recognized. OBJECTIVE: We tested the hypothesis that exposure to
      room light in the late evening suppresses the onset of melatonin synthesis and
      shortens the duration of melatonin production. DESIGN: In a retrospective
      analysis, we compared daily melatonin profiles in individuals living in room
      light (<200 lux) vs. dim light (<3 lux). PATIENTS: Healthy volunteers (n = 116,
      18-30 yr) were recruited from the general population to participate in one of two
      studies. SETTING: Participants lived in a General Clinical Research Center for at
      least five consecutive days. INTERVENTION: Individuals were exposed to room light
      or dim light in the 8 h preceding bedtime. OUTCOME MEASURES: Melatonin duration,
      onset and offset, suppression, and phase angle of entrainment were determined.
      RESULTS: Compared with dim light, exposure to room light before bedtime
      suppressed melatonin, resulting in a later melatonin onset in 99.0% of
      individuals and shortening melatonin duration by about 90 min. Also, exposure to
      room light during the usual hours of sleep suppressed melatonin by greater than
      50% in most (85%) trials. CONCLUSIONS: These findings indicate that room light
      exerts a profound suppressive effect on melatonin levels and shortens the body's
      internal representation of night duration. Hence, chronically exposing oneself to
      electrical lighting in the late evening disrupts melatonin signaling and could
      therefore potentially impact sleep, thermoregulation, blood pressure, and glucose
      homeostasis.

PMID- 21193543
TI  - Genes involved in initial follicle recruitment may be associated with age at
      menopause.
AB  - CONTEXT: Timing of menopause is largely influenced by genetic factors. Because
      menopause occurs when the follicle pool in the ovaries has become exhausted,
      genes involved in primordial follicle recruitment can be considered as candidate
      genes for timing of menopause. OBJECTIVE: The aim was to study the association of
      23 tagging single nucleotide polymorphisms in five genes [Anti-Mullerian hormone
      (AMH), AMH type II receptor (AMHR2), bone morphogenetic protein 15 (BMP15),
      forkhead transcription factor L2 (FOXL2), and growth differentiation factor-9
      (GDF9)] involved in recruitment of the primary follicle pool, including the AMHR2
      gene, which has recently been associated with age at menopause. DESIGN: We
      conducted a cross-sectional association study. SETTING AND PARTICIPANTS: We
      studied a population-based sample of 3616 Dutch women with natural menopause.
      MAIN OUTCOME MEASURE: We measured age at natural menopause. RESULTS: Both studied
      AMHR2 tagging single nucleotide polymorphisms (rs2002555 and rs11170547) in the
      AMHR2 gene were associated with age at natural menopause in interaction with
      parity. Parous rs2002555 G/G carriers had menopause 1 yr later compared with A/A
      carriers (P = 0.01). For rs11170547, each minor allele (T) was associated with a
      0.41-yr later onset of menopause in parous women (P = 0.01). Additionally,
      rs6521896 in BMP15 was associated with later menopause (beta = 0.41; P = 0.007).
      Variants in the AMH, FOXL2, and GDF9 genes were not associated with timing of
      menopause. CONCLUSIONS: The present study confirms an earlier finding that
      variation in the AMHR2 gene modifies the relation between parity and age at
      natural menopause. In combination with the association of BMP15 with menopausal
      age, we find that there is evidence that genes involved in primary follicle
      recruitment influence timing of menopause.

PMID- 21193544
TI  - A novel loss-of-function mutation in GPR54/KISS1R leads to hypogonadotropic
      hypogonadism in a highly consanguineous family.
AB  - CONTEXT: The G protein-coupled receptor 54 (GPR54), the kisspeptin receptor, is
      essential for stimulation of GnRH secretion and induction of puberty. Recently
      loss-of-function mutations of the GPR54 have been implicated as a cause of
      isolated idiopathic hypogonadotropic hypogonadism (IHH). OBJECTIVE: The objective
      of the study was to identify the genetic cause of IHH in a consanguineous
      pedigree and to characterize the phenotypic features from infancy through early
      adulthood. DESIGN: In six patients with normosmic IHH belonging to two families
      of Israeli Muslim-Arab origin highly related to one another, DNA was analyzed for
      mutations in the GnRHR and GPR54 genes, with functional analysis of the mutation
      found. The five males underwent comprehensive endocrine evaluation and were under
      longitudinal follow-up; the one female presented in early adulthood. RESULTS: A
      new homozygous mutation (c.T815C) in GPR54 leading to a phenylalanine
      substitution by serine (p.F272S) was detected in all patients. Functional
      analysis showed an almost complete inhibition of kisspeptin-induced GPR54
      signaling and a dramatic decrease of the mutated receptor expression at the cell
      surface. The males exhibited the same clinical features from infancy to
      adulthood, characterized by cryptorchidism, a relatively short penis, and no
      spontaneous pubertal development. The female patient presented at 18 yr with
      impuberism and primary amenorrhea. Repeated stimulation tests demonstrated
      complete gonadotropin deficiency throughout follow-up. CONCLUSION: A novel loss
      of-function mutation (p.F272S) in the GPR54 gene is associated with familial
      normosmic IHH. Underdeveloped external genitalia and impuberism point to the
      major role of GPR54 in the activation of the gonadotropic axis from intrauterine
      life to adulthood.

PMID- 21193545
TI  - Endocrine disruptors and polycystic ovary syndrome (PCOS): elevated serum levels
      of bisphenol A in women with PCOS.
AB  - CONTEXT: Bisphenol A (BPA) is a widespread industrial compound used in the
      synthesis of polycarbonate plastics. In experimental animals, neonatal exposure
      to BPA results in a polycystic ovary-like syndrome (PCOS) in adulthood. A
      bidirectional interaction between androgens and BPA levels has been disclosed.
      OBJECTIVE: To determine BPA levels in PCOS women as well as the association
      between BPA and hormonal/metabolic parameters compared to a control group.
      DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of 71 PCOS (National
      Institutes of Health criteria) and 100 normal women, age- and body mass index
      matched, in a University hospital setting. MAIN OUTCOME MEASURES: Anthropometric,
      hormonal, metabolic parameters and BPA blood levels were determined. Patients
      (PCOS) and controls (C) were further subdivided according to body mass index into
      lean and overweight subgroups, respectively. RESULTS: BPA levels were
      significantly higher in the total PCOS group compared with the controls (1.05+/
      0.56 vs. 0.72+/-0.37 ng/ml, P < 0.001). PCOS women, lean (PCOS-L) and overweight
      (PCOS-OW), had higher BPA levels compared to the corresponding control group lean
      (C-L) and overweight (C-OW): (PCOS-L = 1.13+/-0.63 vs. C-L = 0.70+/-0.36, P <
      0.001) (PCOS-OW = 0.96 +/- 0.46 vs. C-OW = 0.72 +/- 0.39, P < 0.05). A
      significant association of testosterone (r = 0.192, P < 0.05) and androstenedione
      (r = 0.257, P < 0.05) with BPA was observed. Multiple regression analysis for BPA
      showed significant correlation with the existence of PCOS (r = 0.497, P < 0.05).
      BPA was also positively correlated with insulin resistance (Matsuda index) in the
      PCOS group (r = 0.273, P < 0.05). CONCLUSIONS: Higher BPA levels in PCOS women
      compared to controls and a statistically significant positive association between
      androgens and BPA point to a potential role of this endocrine disruptor in PCOS
      pathophysiology.

PMID- 21193546
TI  - Anti-DLL4 inhibits growth and reduces tumor-initiating cell frequency in
      colorectal tumors with oncogenic KRAS mutations.
AB  - KRAS mutations are frequent in colorectal cancer (CRC) and are associated with
      clinical resistance to treatment with the epidermal growth factor receptor (EGFR)
      targeted monoclonal antibodies. Delta-like 4 ligand (DLL4) is an important
      component of the Notch signaling pathway and mediates stem cell self-renewal and
      vascular development. DLL4 inhibition in colon tumor cells reduces tumor growth
      and stem cell frequency. Considering the need for new drugs to treat colon
      cancers with oncogenic KRAS mutations, we examined in this study the efficacy of
      anti-DLL4 antibodies in KRAS mutant tumors in a panel of early passage colon
      tumor xenograft models derived from patients. Consistent with clinical findings,
      mutant KRAS colorectal xenograft tumors were insensitive to the EGFR therapeutic
      antibody cetuximab, whereas KRAS wild-type tumors responded to cetuximab. In
      contrast, anti-DLL4 was efficacious against both wild-type and mutant KRAS colon
      tumors as a single agent and in combination with irinotecan. Further analysis of
      mutant KRAS tumors indicated that the anti-DLL4/irinotecan combination produced a
      significant decrease in colon cancer stem cell frequency while promoting
      apoptosis in tumor cells. Our findings provide a rationale for targeting DLL4
      Notch signaling for improved treatment of CRC patients with activating KRAS
      mutations.

PMID- 21193547
TI  - Characterization of the Dictyostelium homolog of chromatin binding protein DET1
      suggests a conserved pathway regulating cell type specification and developmental
      plasticity.
AB  - DET1 (De-etiolated 1) is a chromatin binding protein involved in developmental
      regulation in both plants and animals. DET1 is largely restricted to
      multicellular eukaryotes, and here we report the characterization of a DET1
      homolog from the social amoeba Dictyostelium discoideum. As in other species,
      Dictyostelium DET1 is nuclear localized. In contrast to other species, where it
      is an essential protein, loss of DET1 is nonlethal in Dictyostelium, although
      viability is significantly reduced. The phenotype of the det1(-) mutant is highly
      pleiotropic and results in a large degree of heterogeneity in developmental
      parameters. Loss of DET1 results in delayed and abnormal development with
      enlarged aggregation territories. Mutant slugs displayed cell type patterning
      with a bias toward the prestalk pathway. A number of DET1-interacting proteins
      are conserved in Dictyostelium, and the apparently conserved role of DET1 in
      regulatory pathways involving the bZIP transcription factors DimB, c-Jun, and HY5
      suggests a highly conserved mechanism regulating development in multicellular
      eukaryotes. While the mechanism by which DET1 functions is unclear, it appears
      that it has a key role in regulation of developmental plasticity and integration
      of information on environmental conditions into the developmental program of an
      organism.

PMID- 21193548
TI  - Global analysis of protein palmitoylation in African trypanosomes.
AB  - Many eukaryotic proteins are posttranslationally modified by the esterification
      of cysteine thiols to long-chain fatty acids. This modification, protein
      palmitoylation, is catalyzed by a large family of palmitoyl acyltransferases that
      share an Asp-His-His-Cys Cys-rich domain but differ in their subcellular
      localizations and substrate specificities. In Trypanosoma brucei, the flagellated
      protozoan parasite that causes African sleeping sickness, protein palmitoylation
      has been observed for a few proteins, but the extent and consequences of this
      modification are largely unknown. We undertook the present study to investigate
      T. brucei protein palmitoylation at both the enzyme and substrate levels.
      Treatment of parasites with an inhibitor of total protein palmitoylation caused
      potent growth inhibition, yet there was no effect on growth by the separate,
      selective inhibition of each of the 12 individual T. brucei palmitoyl
      acyltransferases. This suggested either that T. brucei evolved functional
      redundancy for the palmitoylation of essential palmitoyl proteins or that
      palmitoylation of some proteins is catalyzed by a noncanonical transferase. To
      identify the palmitoylated proteins in T. brucei, we performed acyl biotin
      exchange chemistry on parasite lysates, followed by streptavidin chromatography,
      two-dimensional liquid chromatography-tandem mass spectrometry protein
      identification, and QSpec statistical analysis. A total of 124 palmitoylated
      proteins were identified, with an estimated false discovery rate of 1.0%. This
      palmitoyl proteome includes all of the known palmitoyl proteins in procyclic
      stage T. brucei as well as several proteins whose homologues are palmitoylated in
      other organisms. Their sequences demonstrate the variety of substrate motifs that
      support palmitoylation, and their identities illustrate the range of cellular
      processes affected by palmitoylation in these important pathogens.

PMID- 21193549
TI  - Molecular characterization of propolis-induced cell death in Saccharomyces
      cerevisiae.
AB  - Propolis, a natural product of plant resins, is used by the bees to seal holes in
      their honeycombs and protect the hive entrance. However, propolis has also been
      used in folk medicine for centuries. Here, we apply the power of Saccharomyces
      cerevisiae as a model organism for studies of genetics, cell biology, and
      genomics to determine how propolis affects fungi at the cellular level. Propolis
      is able to induce an apoptosis cell death response. However, increased exposure
      to propolis provides a corresponding increase in the necrosis response. We showed
      that cytochrome c but not endonuclease G (Nuc1p) is involved in propolis-mediated
      cell death in S. cerevisiae. We also observed that the metacaspase YCA1 gene is
      important for propolis-mediated cell death. To elucidate the gene functions that
      may be required for propolis sensitivity in eukaryotes, the full collection of
      about 4,800 haploid S. cerevisiae deletion strains was screened for propolis
      sensitivity. We were able to identify 138 deletion strains that have different
      degrees of propolis sensitivity compared to the corresponding wild-type strains.
      Systems biology revealed enrichment for genes involved in the mitochondrial
      electron transport chain, vacuolar acidification, negative regulation of
      transcription from RNA polymerase II promoter, regulation of macroautophagy
      associated with protein targeting to vacuoles, and cellular response to
      starvation. Validation studies indicated that propolis sensitivity is dependent
      on the mitochondrial function and that vacuolar acidification and autophagy are
      important for yeast cell death caused by propolis.

PMID- 21193550
TI  - Genomewide expression profile analysis of the Candida glabrata Pdr1 regulon.
AB  - The ABC transporters Candida glabrata Cdr1 (CgCdr1), CgPdh1, and CgSnq2 are known
      to mediate azole resistance in the pathogenic fungus C. glabrata. Activating
      mutations in CgPDR1, a zinc cluster transcription factor, result in constitutive
      upregulation of these ABC transporter genes but to various degrees. We examined
      the genomewide gene expression profiles of two matched azole-susceptible and 
      resistant C. glabrata clinical isolate pairs. Of the differentially expressed
      genes identified in the gene expression profiles for these two matched pairs,
      there were 28 genes commonly upregulated with CgCDR1 in both isolate sets
      including YOR1, LCB5, RTA1, POG1, HFD1, and several members of the FLO gene
      family of flocculation genes. We then sequenced CgPDR1 from each susceptible and
      resistant isolate and found two novel activating mutations that conferred
      increased resistance when they were expressed in a common background strain in
      which CgPDR1 had been disrupted. Microarray analysis comparing these reengineered
      strains to their respective parent strains identified a set of commonly
      differentially expressed genes, including CgCDR1, YOR1, and YIM1, as well as
      genes uniquely regulated by specific mutations. Our results demonstrate that
      while CgPdr1 activates a broad repertoire of genes, specific activating mutations
      result in the activation of discrete subsets of this repertoire.

PMID- 21193551
TI  - Advancing the use and quality of peritoneal dialysis by developing a peritoneal
      dialysis satellite center program.
AB  - BACKGROUND: Peritoneal dialysis (PD) is developing rapidly in China, but because
      there are not enough well-trained PD doctors and nurses in more rural areas, this
      expansion is occurring mainly in larger cities. To address this imbalance, our
      center established a PD satellite center program across Guangdong Province, with
      the aim of extending the use and improving the quality of PD. METHODS: Sun Yat
      sen University PD center is responsible for running the satellite program. The PD
      satellite centers are selected using specific criteria. The full-time PD
      physicians and nurses in the satellite centers accept a unified training program
      and treatment practices, and their clinical outcomes are carefully followed by
      our center. RESULTS: The program began in January 2008, and there are now 12 PD
      centers from which 26 doctors and 32 nurses received PD training. Several hundred
      patients are now receiving PD through this program. The total number of PD
      patients treated by our center and the satellites increased to 1860 from 1010.
      The number treated in the satellite units increased to 1165 from 601. The annual
      dropout rate fell to 17.6% from 28.2%, and the average peritonitis incidence fell
      from 1 episode in 39.4 patient-months to 1 episode in 46.2 patient-months. The 1
      year patient and technique survival rates increased to 84.2% from 82.0% and to
      93% from 88.7% respectively. CONCLUSIONS: Our PD satellite center program is a
      good model for increasing the use and improving the quality of PD in rural areas.
      We plan to expand this program to other parts of southern China.

PMID- 21193552
TI  - Dissociative conscious sedation, an alternative to general anesthesia for
      laparoscopic peritoneal dialysis catheter implantation: a randomized trial
      comparing intravenous and subcutaneous ketamine.
AB  - Laparoscopy is an effective method of implantation for peritoneal dialysis (PD)
      catheters. Use of the laparoscopic technique is increasing because of its
      potential advantages over other techniques. In most patients, selection for PD is
      based on negative criteria, and because of the need for general anesthesia, the
      laparoscopic technique can be life-threatening in these patients. On the other
      hand, local anesthesia is insufficient for laparoscopic catheter implantation. To
      avoid the need for general anesthesia and to achieve patient safety and
      satisfaction, we designed a type of conscious sedation (dissociative conscious
      sedation) and compared the efficacy of subcutaneous (SC) and intravenous (IV)
      ketamine added to narcotics in patients scheduled for laparoscopic implantation
      of a PD catheter. METHODS: Our prospective randomized double-blind study enrolled
      60 adult patients with chronic renal failure who were scheduled for laparoscopic
      implantation of a PD catheter. Patients were randomly assigned to one of two
      groups: one receiving IV ketamine, and the other receiving SC ketamine. In both
      groups, patients were premedicated with IV midazolam 0.015 mg/kg, fentanyl 1-2
      MUg/kg, and lidocaine 1.5 mg/kg. Patients then received 0.6 mg/kg ketamine either
      intravenously (IV group) or by subcutaneous injection at the anterior aspect of
      the forearm (SC group). If systolic blood pressure (BP) increased more than 20%
      from baseline or exceeded 170 mmHg, IV nitroglycerine (TNG) 50 MUg was
      administered incrementally (repeated 50-MUg doses). After a desirable level of
      conscious sedation was achieved, local anesthesia and nitrous oxide
      pneumoperitoneum were applied, and the PD catheter was implanted under
      laparoscopic guidance. Heart rate and BP were measured throughout the procedure.
      Adverse effects and recovery events were recorded. RESULTS: All patients
      tolerated the procedure well. Administration of TNG was significantly more
      frequent in the IV ketamine group. Pain intensity during the surgery was similar
      in both groups. Both groups were comparable with regard to heart rate, but
      patients in the SC ketamine group had a significantly lower systolic BP at the
      2nd measurement and a lower rate-pressure product at the 2nd, 4th, and 5th
      measurements. All patients in the SC ketamine group were cooperative during
      surgery and experienced uneventful recoveries; mild hallucinations were observed
      in 5 patients in the IV ketamine group. In the IV ketamine group, 3 patients lost
      the ability to cooperate during surgery. All catheters were successfully placed.
      CONCLUSIONS: Dissociative conscious sedation is an acceptable alternative to
      general anesthesia in laparoscopic implantation of the PD catheter. Ketamine by
      the SC route is as effective as, but safer than, IV ketamine.

PMID- 21193553
TI  - Peritoneal dialysis fluid induces p38-dependent inflammation in human mesothelial
      cells.
AB  - BACKGROUND: Noninfectious upregulation of proinflammatory pathways in mesothelial
      cells may represent an integral part of their stress response upon exposure to
      peritoneal dialysis fluids (PDF). OBJECTIVE: The aim of this study was to
      evaluate the role of the stress-inducible mitogen-activated protein kinase (MAPK)
      p38 in regulation of inflammatory and stress responses in mesothelial cells
      following in vitro exposure to PDF. MATERIALS AND METHODS: Human peritoneal
      mesothelial cells were exposed to Dianeal PD4 or Physioneal (Baxter AG, Vienna,
      Austria) containing 1.36% glucose and then allowed to recover. Phosphorylation of
      p38, induction of heat shock protein-70 (HSP70), release of lactate dehydrogenase
      (LDH), secretion of interleukin (IL)-8, gene transcription, and mRNA stability
      were assessed with and without the MAPK p38 inhibitor SB203580. RESULTS: Exposure
      to Dianeal resulted in phosphorylation of p38 within 30 minutes (309% of control,
      p < 0.05) and increased IL-8 release (370% of control, p < 0.05), HSP70
      expression (151% of control, p < 0.05), and LDH release (180% of control, p <
      0.05). Exposure to Physioneal resulted in attenuated changes in IL-8, HSP70, and
      LDH. Addition of the p38 inhibitor SB203580 to Dianeal resulted in dampened IL-8
      release (-55%; p < 0.05) and basal HSP70 expression, and unchanged LDH release.
      Effects of p38 on IL-8 were at transcriptional, posttranscriptional, and
      translational levels. CONCLUSION: These data confirm concordant p38-dependent
      upregulation of IL-8 and HSP70 following exposure to bioincompatible PDF. The
      MAPK p38 pathway therefore links proinflammatory processes and the cellular
      stress response in human peritoneal mesothelial cells.

PMID- 21193554
TI  - A novel functional role for the oocyte-specific transcription factor newborn
      ovary homeobox (NOBOX) during early embryonic development in cattle.
AB  - Newborn ovary homeobox (NOBOX) is an oocyte-specific transcription factor
      essential for folliculogenesis and expression of many germ cell-specific genes in
      mice. Here we report the characterization of the bovine NOBOX gene and its role
      in early embryogenesis. The cloned cDNA for bovine NOBOX contains an open reading
      frame encoding a protein of 500 amino acids with a conserved homeodomain. mRNA
      for NOBOX is preferentially expressed in ovaries and undetectable by RT-PCR in
      somatic tissues examined. NOBOX protein is present in oocytes throughout
      folliculogenesis. NOBOX is expressed in a stage-specific manner during oocyte
      maturation and early embryonic development and of maternal origin. Knockdown of
      NOBOX in early embryos using small interfering RNA demonstrated that NOBOX is
      required for embryonic development to the blastocyst stage. Depletion of NOBOX in
      early embryos caused significant down-regulation of genes associated with
      transcriptional regulation, signal transduction, and cell cycle regulation during
      embryonic genome activation. In addition, NOBOX depletion in early embryos
      reduced expression of pluripotency genes (POU5F1/OCT4 and NANOG) and number of
      inner cell mass cells in embryos that reached the blastocyst stage. This study
      demonstrates that NOBOX is an essential maternal-derived transcription factor
      during bovine early embryogenesis, which functions in regulation of embryonic
      genome activation, pluripotency gene expression, and blastocyst cell allocation.

PMID- 21193555
TI  - Cytoplasmic accumulation of incompletely glycosylated SHBG enhances androgen
      action in proximal tubule epithelial cells.
AB  - Human sex hormone-binding globulin (SHBG) accumulates within the cytoplasm of
      epithelial cells lining the proximal convoluted tubules of mice expressing human
      SHBG transgenes. The main ligands of SHBG, testosterone and its metabolite,
      5alpha-dihydrotestosterone (DHT), alter expression of androgen-responsive genes
      in the kidney. To determine how intracellular SHBG might influence androgen
      action, we used a mouse proximal convoluted tubule (PCT) cell line with
      characteristics of S1/S2 epithelial cells in which human SHBG accumulates.
      Western blotting revealed that SHBG extracted from PCT cells expressing a human
      SHBG cDNA (PCT-SHBG) is 5-8 kDa smaller than the SHBG secreted by these cells,
      due to incomplete N-glycosylation and absence of O-linked oligosaccharides. PCT
      SHBG cells sequester [(3)H]DHT more effectively from culture medium than parental
      PCT cells, and the presence of SHBG accentuates androgen-dependent activation of
      a luciferase reporter gene, as well as the endogenous kidney androgen-regulated
      protein (Kap) gene. After androgen withdrawal, androgen-induced Kap mRNA levels
      in PCT-SHBG cells are maintained for more than 2 wk vs 2 d in parental PCT cells.
      Transcriptome profiling after testosterone or DHT pretreatments, followed by 3 d
      of steroid withdrawal, also demonstrated that intracellular SHBG enhances
      androgen-dependent stimulation (e.g. Adh7, Vcam1, Areg, Tnfaip2) or repression
      (e.g. Cldn2 and Osr2) of many other genes in PCT cells. In addition, nuclear
      localization of the androgen receptor is enhanced and retained longer after
      steroid withdrawal in PCT cells containing functional SHBG. Thus, intracellular
      SHBG accentuates the uptake of androgens and sustains androgens access to the
      androgen receptor, especially under conditions of limited androgen supply.

PMID- 21193556
TI  - A pituitary-specific enhancer of the POMC gene with preferential activity in
      corticotrope cells.
AB  - Cell-specific expression of the pituitary proopiomelanocortin (POMC) gene depends
      on the combination of tissue- and cell-restricted transcription factors such as
      Pitx1 and Tpit. These factors act on the proximal POMC promoter together with
      transcription factors that integrate inputs from signaling pathways. We now
      report the identification of an upstream enhancer in the POMC locus that is
      targeted by the same subset of transcription factors, except Pitx1. This enhancer
      located at -7 kb in the mouse POMC gene is highly dependent on Tpit for activity.
      Whereas Tpit requires Pitx1 for action on the promoter, it acts on the -7-kb
      enhancer as homodimers binding to a palindromic Tpit response element (TpitRE).
      Both half-sites of the TpitRE palindrome and Tpit homodimerization are required
      for activity. In vivo, the enhancer exhibits preferential activity in
      corticotrope cells of the anterior lobe whereas the promoter exhibits preference
      for intermediate lobe melanotropes. The enhancer is conserved among different
      species with the TpitRE palindrome localized at the center of conserved
      sequences. However, the mouse and human -7-kb enhancers do not exhibit
      conservation of hormone responsiveness and may differ in their relative
      importance for POMC expression. In summary, pituitary expression of the POMC gene
      relies on an upstream enhancer that complements the activity of the proximal
      promoter with Tpit as the major regulator of both regulatory regions.

PMID- 21193557
TI  - Hnf1alpha (MODY3) regulates beta-cell-enriched MafA transcription factor
      expression.
AB  - The expression pattern of genes important for pancreatic islet cell function
      requires the actions of cell-enriched transcription factors. Musculoaponeurotic
      fibrosarcoma homolog A (MafA) is a beta-cell-specific transcriptional activator
      critical to adult islet beta-cell function, with MafA mutant mice manifesting
      symptoms associated with human type 2 diabetes. Here, we describe that MafA
      expression is controlled by hepatocyte nuclear factor 1-alpha (Hnf1alpha), the
      transcription factor gene mutated in the most common monoallelic form of maturity
      onset diabetes of the young. There are six conserved sequence domains in the 5'
      flanking MafA promoter, of which one, region 3 (R3) [base pair (bp) -8118/-7750]
      is principally involved in controlling the unique developmental and adult islet
      beta-cell-specific expression pattern. Chromatin immunoprecipitation analysis
      demonstrated that Hnf1alpha bound specifically within R3. Furthermore, in vitro
      DNA-binding experiments localized an Hnf1alpha regulatory element between bp 
      7822 and -7793, an area previously associated with stimulation by the islet
      developmental regulator, Islet1. However, site-directed mutational studies showed
      that Hnf1alpha was essential to R3-driven reporter activation through bp -7816/
      7811. Significantly, MafA levels were dramatically reduced in the insulin(+) cell
      population remaining in embryonic and adult Hnf1alpha(-/-) pancreata. Our results
      demonstrate that Hnf1alpha regulates MafA in beta-cells and suggests that
      compromised MafA expression contributes to beta-cell dysfunction in maturity
      onset diabetes of the young.

PMID- 21193558
TI  - 37-kDa laminin receptor precursor mediates GnRH-II-induced MMP-2 expression and
      invasiveness in ovarian cancer cells.
AB  - GnRH-II enhances ovarian cancer cell invasion in an autocrine manner. We have now
      found that GnRH-II increases 37-kDa laminin receptor precursor (LRP) production
      in GnRH receptor (GnRHR)-positive OVCAR-3 and CaOV-3 ovarian cancer cells, while
      small interfering RNA (siRNA)-mediated depletion of GnRH-II or GnRHR mRNA
      abrogates this. The invasiveness of ovarian cancer cells is also reduced >85% by
      siRNA-mediated knockdown of LRP levels and >50% by pretreatment of Matrigel with
      a synthetic peptide that blocks interactions between laminin and the 67-kDa
      nonintegrin laminin receptor which comprises two LRP subunits. Conversely,
      overexpressing LRP in CaOV-3 cells increases their invasiveness 5-fold, while
      overexpressing LRP with a nonfunctional laminin-binding site does not. Depletion
      of LRP by siRNA treatment reduces CaOV-3 cell attachment to laminin-coated plates
      by ~80% but only reduces their binding to Matrigel by ~20%. Thus, while LRP
      influences CaOV-3 cell adhesion to laminin, LRP must act in other ways to enhance
      invasion. Matrix metalloproteinases (MMPs) are key mediators of invasion, and LRP
      siRNA treatment of OVCAR-3 and CaOV-3 cells inhibits MMP-2 but not MMP-9 mRNA
      levels. Overexpressing LRP in these cells increases MMP-2 production
      specifically, while a laminin-binding deficient LRP does not. Importantly, LRP
      siRNA treatment abolishes GnRH-II-induced MMP-2 production, and invasion in OVCAR
      3 and CaOV-3 cells, which was also seen after MMP-2 siRNA treatment. These
      results suggest that GnRH-II-induced LRP expression increases the amount of the
      67-kDa nonintegrin laminin receptor, which appears to interact with laminin in
      the extracellular matrix to promote MMP-2 expression and enhance ovarian cancer
      cell invasion.

PMID- 21193560
TI  - The microbubble or the microparticle?

PMID- 21193559
TI  - PERK activation at low glucose concentration is mediated by SERCA pump inhibition
      and confers preemptive cytoprotection to pancreatic beta-cells.
AB  - Protein kinase R-like ER kinase (PERK) is activated at physiologically low
      glucose concentrations in pancreatic beta-cells. However, the molecular
      mechanisms by which PERK is activated under these conditions and its role in beta
      cell function are poorly understood. In this report, we investigated, in
      dispersed rat islets of Langerhans and mouse insulinoma-6 (MIN6) cells, the
      relationship between extracellular glucose concentration, the free endoplasmic
      reticulum (ER) calcium concentration ([Ca(2+)](ER)) measured directly using an ER
      targeted fluorescence resonance energy transfer-based calcium sensor, and the
      activation of PERK. We found that a decrease in glucose concentration leads to a
      concentration-dependent reduction in [Ca(2+)](ER) that parallels the activation
      of PERK and the phosphorylation of its substrate eukaryotic initiation factor
      2alpha. We provide evidence that this decrease in [Ca(2+)](ER) is caused by a
      decrease in sarcoplasmic/ER Ca(2+)-ATPase pump activity mediated by a reduction
      in the energy status of the cell. Importantly, we also report that PERK-dependent
      eukaryotic initiation factor-2alpha phosphorylation at low glucose concentration
      plays a significant role in 1) the regulation of both proinsulin and global
      protein synthesis, 2) cell viability, and 3) conferring preemptive cytoprotection
      against ER stress. Taken together, these results provide evidence that a decrease
      in the ATP/energy status of the cell in response to a decrease in glucose
      concentration results in sarcoplasmic/ER Ca(2+)-ATPase pump inhibition, the
      efflux of Ca(2+) from the ER, and the activation of PERK, which plays an
      important role in both pancreatic beta-cell function and survival.

PMID- 21193561
TI  - When less is more: a simple Western blotting amendment allowing data acquisition
      on human single fibers.

PMID- 21193563
TI  - Differential contribution of central command to the cardiovascular responses
      during static exercise of ankle dorsal and plantar flexion in humans.
AB  - To examine whether central command contributes differently to the cardiovascular
      responses during voluntary static exercise engaged by different muscle groups, we
      encouraged healthy subjects to perform voluntary and electrically evoked
      involuntary static exercise of ankle dorsal and plantar flexion. Each exercise
      was conducted with 25% of the maximum voluntary force of the right ankle dorsal
      and plantar flexion, respectively, for 2 min. Heart rate (HR) and mean arterial
      blood pressure (MAP) were recorded, and stroke volume, cardiac output (CO), and
      total peripheral resistance were calculated. With voluntary exercise, HR, MAP,
      and CO significantly increased during dorsal flexion (the maximum increase, HR:
      12 +/- 2.3 beats/min; MAP: 14 +/- 2.0 mmHg; CO: 1 +/- 0.2 l/min), whereas only
      MAP increased during plantar flexion (the maximum increase, 6 +/- 2.0 mmHg).
      Stroke volume and total peripheral resistance were unchanged throughout the two
      kinds of voluntary static exercise. With involuntary exercise, there were no
      significant changes in all cardiovascular variables, irrespective of dorsal or
      plantar flexion. Furthermore, before the force onset of voluntary static
      exercise, HR and MAP started to increase without muscle contraction, whereas they
      had no significant changes with involuntary exercise at the moment. The present
      findings indicate that differential contribution of central command is
      responsible for the different cardiovascular responses to static exercise,
      depending on the strength of central control of the contracting muscle.

PMID- 21193562
TI  - Chronic heart failure reduces Akt phosphorylation in human skeletal muscle:
      relationship to muscle size and function.
AB  - Patients with chronic heart failure (HF) frequently lose muscle mass and function
      during the course of the disease. A reduction in anabolic stimuli to the muscle
      has been put forth as a potential mechanism underlying these alterations. The
      present study examined the hypothesis that skeletal muscle tissue from HF
      patients would show reduced IGF-1 expression and phosphorylation of signaling
      molecules downstream of receptor activation. To isolate the unique effect of HF
      on these variables, we limited the confounding effects of muscle disuse and/or
      acute disease exacerbation by recruiting controls (n = 11) with similar physical
      activity levels as HF patients (n = 11) and by testing patients at least 6 mo
      following any bouts of disease exacerbation/hospitalization. IGF-1 expression in
      skeletal muscle was similar between patients and controls. Despite this, HF
      patients were characterized by reduced levels of phospho-Akt/Akt (S473; -43%; P <
      0.05), whereas no differences were found in total Akt protein content or phospho-
      or total protein content of mammalian target of rapamycin (mTOR; S2448), glycogen
      synthase kinase-3beta (GSK-3beta; S9), eukaryotic translation initiation factor
      4E binding protein-1 (eIF4E-BP; T37/46), p70 ribosomal S6 kinase (p70 S6K; T389),
      or eIF2Bepsilon (S540). Reduced phospho-Akt/Akt levels and phospho-mTOR/mTOR were
      related to decreased skeletal muscle myosin protein content (r = 0.602; P < 0.02)
      and knee extensor isometric torque (r = 0.550; P < 0.05), respectively. Because
      patients and controls were similar for age, muscle mass, and physical activity,
      we ascribe the observed alterations in Akt phosphorylation and its relationship
      to myosin protein content to the unique effects of the HF syndrome.

PMID- 21193564
TI  - Associations between sports participation, cardiorespiratory fitness, and
      adiposity in young adult twins.
AB  - Exercise behavior, cardiorespiratory fitness, and obesity are strongly influenced
      by genetic factors. By studying young adult twins, we examined to what extent
      these interrelated traits have shared genetic and environmental etiologies. We
      studied 304 twin individuals selected from the population-based FinnTwin16 study.
      Physical activity was assessed with the Baecke questionnaire, yielding three
      indexes: sport index, leisure-time index, and work index. In this study, we
      focused on sport index, which describes sports participation. Body composition
      was determined using dual-energy X-ray absorptiometry and cardiorespiratory
      fitness using a bicycle ergometer exercise test with gas exchange analysis. The
      Baecke sport index was associated with high maximal oxygen uptake adjusted for
      lean body mass (Vo(2max)[adj]) (r = 0.40), with low body fat percentage (BF%) (r
      = -0.44) and low waist circumference (WC) (r = -0.29). Heritability estimates for
      the key traits were as follows: 56% for sport index, 71% for Vo(2max)[adj], 77%
      for body mass index, 66% for WC, and 68% for BF%. The association between sport
      index and Vo(2max) was mostly explained by genetic factors (70%), as were both
      the association between sport index and BF% (71%) and that between sport index
      and WC (59%). Our results suggest that genetic factors explain a considerable
      part of the associations between sports participation, cardiorespiratory fitness,
      and obesity.

PMID- 21193565
TI  - Nitric oxide-mediated vasodilation becomes independent of beta-adrenergic
      receptor activation with increased intensity of hypoxic exercise.
AB  - Hypoxic vasodilation in skeletal muscle at rest is known to include beta
      adrenergic receptor-stimulated nitric oxide (NO) release. We previously reported
      that the augmented skeletal muscle vasodilation during mild hypoxic forearm
      exercise includes beta-adrenergic mechanisms. However, it is unclear whether a
      beta-adrenergic receptor-stimulated NO component exists during hypoxic exercise.
      We hypothesized that NO-mediated vasodilation becomes independent of beta
      adrenergic receptor activation with increased exercise intensity during hypoxic
      exercise. Ten subjects (7 men, 3 women; 23 +/- 1 yr) breathed hypoxic gas to
      titrate arterial O(2) saturation to 80% while remaining normocapnic. Subjects
      performed two consecutive bouts of incremental rhythmic forearm exercise (10% and
      20% of maximum) with local administration (via a brachial artery catheter) of
      propranolol (beta-adrenergic receptor inhibition) alone and with the combination
      of propranolol and nitric oxide synthase inhibition [N(G)-monomethyl-l-arginine
      (l-NMMA)] under normoxic and hypoxic conditions. Forearm blood flow (FBF, ml/min;
      Doppler ultrasound) and blood pressure [mean arterial pressure (MAP), mmHg;
      brachial artery catheter] were assessed, and forearm vascular conductance (FVC,
      ml.min(-1).100 mmHg(-1)) was calculated (FBF/MAP). During propranolol alone, the
      rise in FVC (Delta from normoxic baseline) due to hypoxic exercise was 217 +/- 29
      and 415 +/- 41 ml.min(-1).100 mmHg(-1) (10% and 20% of maximum, respectively).
      Combined propranolol-l-NMMA infusion during hypoxic exercise attenuated DeltaFVC
      at 20% (352 +/- 44 ml.min(-1).100 mmHg(-1); P < 0.001) but not at 10% (202 +/- 28
      ml.min(-1).100 mmHg(-1); P = 0.08) of maximum compared with propranolol alone.
      These data, when integrated with earlier findings, demonstrate that NO
      contributes to the compensatory vasodilation during mild and moderate hypoxic
      exercise; a beta-adrenergic receptor-stimulated NO component exists during low
      intensity hypoxic exercise. However, the source of the NO becomes less dependent
      on beta-adrenergic mechanisms as exercise intensity increases.

PMID- 21193566
TI  - Effect of daily noise exposure monitoring on annual rates of hearing loss in
      industrial workers.
AB  - OBJECTIVES: Occupational noise-induced hearing loss (NIHL) is prevalent, yet
      evidence on the effectiveness of preventive interventions is lacking. The
      effectiveness of a new technology allowing workers to monitor daily at-ear noise
      exposure was analysed. METHODS: Workers in the hearing conservation program of an
      aluminium smelter were recruited because of accelerated rates of hearing loss.
      The intervention consisted of daily monitoring of at-ear noise exposure and
      regular feedback on exposures from supervisors. The annual rate of change in high
      frequency hearing average at 2, 3 and 4 KHz before intervention (2000-2004) and 4
      years after intervention (2006-2009) was determined. Annual rates of loss were
      compared between 78 intervention subjects and 234 controls in other company
      smelters matched for age, gender and high frequency hearing threshold level in
      2005. RESULTS: Individuals monitoring daily noise exposure experienced on average
      no further worsening of high frequency hearing (average rate of hearing change at
      2, 3 and 4 KHz = -0.5 dB/year). Matched controls also showed decelerating hearing
      loss, the difference in rates between the two groups being significant (p <
      0.0001). Analysis of a subset of intervention subjects matched to controls for
      initial rate of hearing loss showed a similar trend but the difference was not
      statistically significant (p = 0.06). CONCLUSION: Monitoring daily occupational
      noise exposure inside hearing protection with ongoing administrative feedback
      apparently reduces the risk of occupational NIHL in industrial workers. Longer
      follow-up of these workers will help determine the significance of the
      intervention effect. Intervention studies for the prevention of NIHL need to
      include appropriate control groups.

PMID- 21193567
TI  - The contribution of major risk factors and job strain to occupational class
      differences in coronary heart disease incidence: the MONICA Brianza and PAMELA
      population-based cohorts.
AB  - OBJECTIVES: We investigated the contribution of major coronary heart disease
      (CHD) risk factors and job strain to occupational class differences in CHD
      incidence in a pooled-cohort prospective study in northern Italy. METHODS: 2964
      men aged 25-74 from four northern Italian population-based cohorts were
      investigated at baseline and followed for first fatal or non-fatal CHD event (171
      events). Standardised procedures were used for baseline risk factor measurements,
      follow-up and validation of CHD events. Four occupational classes were derived
      from the Erikson-Goldthorpe-Portocarero social class scheme: higher and lower
      professionals and administrators, non-manual workers, skilled and unskilled
      manual workers, and the self-employed. HRs were estimated with Cox models.
      RESULTS: Among CHD-free subjects, with non-manual workers as the reference group,
      age-adjusted excess risks were found for professionals and administrators (+84%,
      p=0.02), the self-employed (+72%, p=0.04) and manual workers (+63%, p=0.04). The
      relationship was consistent across different CHD diagnostic categories. Adjusting
      for major risk factors only slightly reduced the reported excess risks. In a sub
      sample of currently employed subjects, adjusting for major risk factors, sport
      physical activity and job strain reduced the excess risk for manual workers
      (relative change = -71.4%) but did not substantially modify the excess risks of
      professionals and administrators and the self-employed. CONCLUSIONS: In our
      study, we found higher CHD incidence rates for manual workers, professionals and
      administrators, and the self-employed, compared to non-manual workers. When the
      entire spectrum of job categories is considered, the job strain model helped
      explain the CHD excess risk for manual workers but not for other occupational
      classes.

PMID- 21193568
TI  - Ultrasound performs better than radiographs.

PMID- 21193569
TI  - Hospital admission rates for COPD: the inverse care law is alive and well.

PMID- 21193571
TI  - Arabidopsis NPCC6/NaKR1 is a phloem mobile metal binding protein necessary for
      phloem function and root meristem maintenance.
AB  - SODIUM POTASSIUM ROOT DEFECTIVE1 (NaKR1; previously called NPCC6) encodes a
      soluble metal binding protein that is specifically expressed in companion cells
      of the phloem. The nakr1-1 mutant phenotype includes high Na(+), K(+), Rb(+), and
      starch accumulation in leaves, short roots, late flowering, and decreased long
      distance transport of sucrose. Using traditional and DNA microarray-based
      deletion mapping, a 7-bp deletion was found in an exon of NaKR1 that introduced a
      premature stop codon. The mutant phenotypes were complemented by transformation
      with the native gene or NaKR1-GFP (green fluorescent protein) and NaKR1-beta
      glucuronidase fusions driven by the native promoter. NAKR1-GFP was mobile in the
      phloem; it moved from companion cells into sieve elements and into a previously
      undiscovered symplasmic domain in the root meristem. Grafting experiments
      revealed that the high Na(+) accumulation was due mainly to loss of NaKR1
      function in the leaves. This supports a role for the phloem in recirculating
      Na(+) to the roots to limit Na(+) accumulation in leaves. The onset of root
      phenotypes coincided with NaKR1 expression after germination. The nakr1-1 short
      root phenotype was due primarily to a decreased cell division rate in the root
      meristem, indicating a role in root meristem maintenance for NaKR1 expression in
      the phloem.

PMID- 21193570
TI  - LAP6/POLYKETIDE SYNTHASE A and LAP5/POLYKETIDE SYNTHASE B encode hydroxyalkyl
      alpha-pyrone synthases required for pollen development and sporopollenin
      biosynthesis in Arabidopsis thaliana.
AB  - Plant type III polyketide synthases (PKSs) catalyze the condensation of malonyl
      CoA units with various CoA ester starter molecules to generate a diverse array of
      natural products. The fatty acyl-CoA esters synthesized by Arabidopsis thaliana
      ACYL-COA SYNTHETASE5 (ACOS5) are key intermediates in the biosynthesis of
      sporopollenin, the major constituent of exine in the outer pollen wall. By
      coexpression analysis, we identified two Arabidopsis PKS genes, POLYKETIDE
      SYNTHASE A (PKSA) and PKSB (also known as LAP6 and LAP5, respectively) that are
      tightly coexpressed with ACOS5. Recombinant PKSA and PKSB proteins generated tri
      and tetraketide alpha-pyrone compounds in vitro from a broad range of potential
      ACOS5-generated fatty acyl-CoA starter substrates by condensation with malonyl
      CoA. Furthermore, substrate preference profile and kinetic analyses strongly
      suggested that in planta substrates for both enzymes are midchain- and omega
      hydroxylated fatty acyl-CoAs (e.g., 12-hydroxyoctadecanoyl-CoA and 16
      hydroxyhexadecanoyl-CoA), which are the products of sequential actions of anther
      specific fatty acid hydroxylases and acyl-CoA synthetase. PKSA and PKSB are
      specifically and transiently expressed in tapetal cells during microspore
      development in Arabidopsis anthers. Mutants compromised in expression of the PKS
      genes displayed pollen exine layer defects, and a double pksa pksb mutant was
      completely male sterile, with no apparent exine. These results show that
      hydroxylated alpha-pyrone polyketide compounds generated by the sequential action
      of ACOS5 and PKSA/B are potential and previously unknown sporopollenin
      precursors.

PMID- 21193572
TI  - Analysis of TETRAKETIDE alpha-PYRONE REDUCTASE function in Arabidopsis thaliana
      reveals a previously unknown, but conserved, biochemical pathway in sporopollenin
      monomer biosynthesis.
AB  - The precise structure of the sporopollenin polymer that is the major constituent
      of exine, the outer pollen wall, remains poorly understood. Recently,
      characterization of Arabidopsis thaliana genes and corresponding enzymes involved
      in exine formation has demonstrated the role of fatty acid derivatives as
      precursors of sporopollenin building units. Fatty acyl-CoA esters synthesized by
      ACYL-COA SYNTHETASE5 (ACOS5) are condensed with malonyl-CoA by POLYKETIDE
      SYNTHASE A (PKSA) and PKSB to yield alpha-pyrone polyketides required for exine
      formation. Here, we show that two closely related genes encoding oxidoreductases
      are specifically and transiently expressed in tapetal cells during microspore
      development in Arabidopsis anthers. Mutants compromised in expression of the
      reductases displayed a range of pollen exine layer defects, depending on the
      mutant allele. Phylogenetic studies indicated that the two reductases belong to a
      large reductase/dehydrogenase gene family and cluster in two distinct clades with
      putative orthologs from several angiosperm lineages and the moss Physcomitrella
      patens. Recombinant proteins produced in bacteria reduced the carbonyl function
      of tetraketide alpha-pyrone compounds synthesized by PKSA/B, and the proteins
      were therefore named TETRAKETIDE alpha-PYRONE REDUCTASE1 (TKPR1) and TKPR2
      (previously called DRL1 and CCRL6, respectively). TKPR activities, together with
      those of ACOS5 and PKSA/B, identify a conserved biosynthetic pathway leading to
      hydroxylated alpha-pyrone compounds that were previously unknown to be
      sporopollenin precursors.

PMID- 21193573
TI  - EXPO, an exocyst-positive organelle distinct from multivesicular endosomes and
      autophagosomes, mediates cytosol to cell wall exocytosis in Arabidopsis and
      tobacco cells.
AB  - The exocyst protein complex mediates vesicle fusion with the plasma membrane. By
      expressing an (X)FP-tagged Arabidopsis thaliana homolog of the exocyst protein
      Exo70 in suspension-cultured Arabidopsis and tobacco (Nicotiana tabacum) BY-2
      cells, and using antibodies specific for Exo70, we detected a compartment, which
      we term EXPO (for exocyst positive organelles). Standard markers for the Golgi
      apparatus, the trans-Golgi network/early endosome, and the multivesicular
      body/late endosome in plants do not colocalize with EXPO. Inhibitors of the
      secretory and endocytic pathways also do not affect EXPO. Exo70E2-(X)FP also
      locates to the plasma membrane (PM) as discrete punctae and is secreted outside
      of the cells. Immunogold labeling of sections cut from high-pressure frozen
      samples reveal EXPO to be spherical double membrane structures resembling
      autophagosomes. However, unlike autophagosomes, EXPOs are not induced by
      starvation and do not fuse with the lytic compartment or with endosomes. Instead,
      they fuse with the PM, releasing a single membrane vesicle into the cell wall.
      EXPOs are also found in other cell types, including root tips, root hair cells,
      and pollen grains. EXPOs therefore represent a form of unconventional secretion
      unique to plants.

PMID- 21193574
TI  - Identification and utilization of a sow thistle powdery mildew as a poorly
      adapted pathogen to dissect post-invasion non-host resistance mechanisms in
      Arabidopsis.
AB  - To better dissect non-host resistance against haustorium-forming powdery mildew
      pathogens, a sow thistle powdery mildew isolate designated Golovinomyces
      cichoracearum UMSG1 that has largely overcome penetration resistance but is
      invariably stopped by post-invasion non-host resistance of Arabidopsis thaliana
      was identified. The post-invasion non-host resistance is mainly manifested as the
      formation of a callosic encasement of the haustorial complex (EHC) and
      hypersensitive response (HR), which appears to be controlled by both salicylic
      acid (SA)-dependent and SA-independent defence pathways, as supported by the
      susceptibility of the pad4/sid2 double mutant to the pathogen. While the broad
      spectrum resistance protein RPW8.2 enhances post-penetration resistance against
      G. cichoracearum UCSC1, a well-adapted powdery mildew pathogen, RPW8.2, is
      dispensable for post-penetration resistance against G. cichoracearum UMSG1, and
      its specific targeting to the extrahaustorial membrane is physically blocked by
      the EHC, resulting in HR cell death. Taken together, the present work suggests an
      evolutionary scenario for the Arabidopsis-powdery mildew interaction: EHC
      formation is a conserved subcellular defence evolved in plants against haustorial
      invasion; well-adapted powdery mildew has evolved the ability to suppress EHC
      formation for parasitic growth and reproduction; RPW8.2 has evolved to enhance
      EHC formation, thereby conferring haustorium-targeted, broad-spectrum resistance
      at the post-invasion stage.

PMID- 21193575
TI  - Cross activity of orthologous WRKY transcription factors in wheat and
      Arabidopsis.
AB  - WRKY proteins are transcription factors involved in many plant processes
      including plant responses to pathogens. Here, the cross activity of TaWRKY78 from
      the monocot wheat and AtWRKY20 from the dicot Arabidopsis on the cognate
      promoters of the orthologous PR4-type genes wPR4e and AtHEL of wheat and
      Arabidopsis, respectively, was investigated. In vitro analysis showed the ability
      of TaWRKY78 to bind a -17/+80 region of the wPR4e promoter, containing one cis
      acting W-box. Moreover, transient expression analysis performed on both TaWRKY78
      and AtWRKY20 showed their ability to recognize the cognate cis-acting elements
      present in the wPR4e and AtHEL promoters, respectively. Finally, this paper
      provides evidence that both transcription factors are able to cross-regulate the
      orthologous PR4 genes with an efficiency slightly lower than that exerted on the
      cognate promoters. The observation that orthologous genes are subjected to
      similar transcriptional control by orthologous transcription factors demonstrates
      that the terminal stages of signal transduction pathways leading to defence are
      conserved and suggests a fundamental role of PR4 genes in plant defence.
      Moreover, these results corroborate the hypothesis that gene orthology imply
      similar gene function and that diversification between monocot and dicot has most
      likely occurred after the specialization of WRKY function.

PMID- 21193576
TI  - Hydraulic efficiency and coordination with xylem resistance to cavitation, leaf
      function, and growth performance among eight unrelated Populus deltoidesxPopulus
      nigra hybrids.
AB  - Tests were carried out to determine whether variations in the hydraulic
      architecture of eight Populus deltoides*Populus nigra genotypes could be related
      to variations in leaf function and growth performance. Measurements were
      performed in a coppice plantation on 1-year-old shoots under optimal irrigation.
      Hydraulic architecture was characterized through estimates of hydraulic
      efficiency (the ratio of conducting sapwood area to leaf area, A(X):A(L); leaf-
      and xylem-specific hydraulic conductance of defoliated shoots, k(SL) and k(SS),
      respectively; apparent whole-plant leaf-specific hydraulic conductance, k(plant))
      and xylem safety (water potential inducing 50% loss in hydraulic conductance).
      The eight genotypes spanned a significant range of k(SL) from 2.63  kg s(-1) m(
      2) MPa(-1) to 4.18  kg s(-1) m(-2) MPa(-1), variations being mostly driven by
      k(SS) rather than A(X):A(L). There was a strong trade-off between hydraulic
      efficiency and xylem safety. Values of k(SL) correlated positively with k(plant),
      indicating that high-pressure flowmeter (HPFM) measurements of stem hydraulic
      efficiency accurately reflected whole-plant water transport efficiency of field
      grown plants at maximum transpiration rate. No clear relationship could be found
      between hydraulic efficiency and either net CO(2) assimilation rates, water-use
      efficiency estimates (intrinsic water-use efficiency and carbon isotope
      discrimination against (13)C), or stomatal characteristics (stomatal density and
      stomatal pore area index). Estimates of hydraulic efficiency were negatively
      associated with relative growth rate. This unusual pattern, combined with the
      trade-off observed between hydraulic efficiency and xylem safety, provides the
      rationale for the positive link already reported between relative growth rate and
      xylem safety among the same eight P. deltoides*P. nigra genotypes.

PMID- 21193577
TI  - Proteome analysis of the Albugo candida-Brassica juncea pathosystem reveals that
      the timing of the expression of defence-related genes is a crucial determinant of
      pathogenesis.
AB  - White rust, caused by Albugo candida, is a serious pathogen of Brassica juncea
      (Indian mustard) and poses a potential hazard to the presently developing canola
      quality B. juncea industry worldwide. A comparative proteomic study was
      undertaken to explore the molecular mechanisms that underlie the defence
      responses of Brassica juncea to white rust disease caused by the biotrophic
      oomycete Albugo candida. Nineteen proteins showed reproducible differences in
      abundance between a susceptible (RH 819) and a resistant variety (CBJ 001) of B.
      juncea following inoculation with A. candida. The identities of all 19 proteins
      were successfully established through Q-TOF MS/MS. Five of these proteins were
      only detected in the resistant variety and showed significant differences in
      their abundance at various times following pathogen inoculation in comparison to
      mock-inoculated plants. Among these was a thaumatin-like protein (PR-5), a
      protein not previously associated with the resistance of B. juncea towards A.
      candida. One protein, peptidyl-prolyl cis/trans isomerase (PPIase) isoform CYP20
      3, was only detected in the susceptible variety and increased in abundance in
      response to the pathogen. PPIases have recently been discovered to play an
      important role in pathogenesis by suppressing the host cell's immune response.
      For a subset of seven proteins examined in more detail, an increase in transcript
      abundance always preceded their induction at the proteome level. These findings
      are discussed within the context of the A. candida-Brassica juncea pathosystem,
      especially in relation to host resistance to this pathogen.

PMID- 21193578
TI  - Drought-induced site-specific DNA methylation and its association with drought
      tolerance in rice (Oryza sativa L.).
AB  - An indica pyramiding line, DK151, and its recurrent parent, IR64, were evaluated
      under drought stress and non-stress conditions for three consecutive seasons.
      DK151 showed significantly improved tolerance to drought. The DNA methylation
      changes in DK151 and IR64 under drought stress and subsequent recovery were
      assessed using methylation-sensitive amplified polymorphism analysis. Our results
      indicate that drought-induced genome-wide DNA methylation changes accounted for
      ~12.1% of the total site-specific methylation differences in the rice genome.
      This drought-induced DNA methylation pattern showed three interesting properties.
      The most important one was its genotypic specificity reflected by large
      differences in the detected DNA methylation/demethylation sites between DK151 and
      IR64, which result from introgressed genomic fragments in DK151. Second, most
      drought-induced methylation/demethylation sites were of two major types
      distinguished by their reversibility, including 70% of the sites at which drought
      induced epigenetic changes were reversed to their original status after recovery,
      and 29% of sites at which the drought-induced DNA demethylation/methylation
      changes remain even after recovery. Third, the drought-induced DNA methylation
      alteration showed a significant level of developmental and tissue specificity.
      Together, these properties are expected to have contributed greatly to rice
      response and adaptation to drought stress. Thus, induced epigenetic changes in
      rice genome can be considered as a very important regulatory mechanism for rice
      plants to adapt to drought and possibly other environmental stresses.

PMID- 21193579
TI  - From the soil to the seeds: the long journey of nitrate in plants.
AB  - Under temperate climates and in cultivated soils, nitrate is the most important
      source of nitrogen (N) available for crops and, before its reduction and
      assimilation into amino acids, must enter the root cells and then move in the
      whole plant. The aim of this review is to provide an overall picture of the
      numerous membrane proteins that achieve these processes by being localized in
      different compartments and in different tissues. Nitrate transporters (NRT) from
      the NRT1 and NRT2 families ensure the capacity of root cells to take up nitrate,
      through high- and low-affinity systems (HATS and LATS) depending on nitrate
      concentrations in the soil solution. Other members of the NRT1 family are
      involved subsequently in loading and unloading of nitrate to and from the xylem
      vessels, allowing its distribution to aerial organs or its remobilization from
      old leaves. Once in the cell, nitrate can be stored in the vacuole by passing
      through the tonoplast, a step that involves chloride channels (CLC) or a NRT2
      member. Finally, with the exception of one NRT1 member, the transport of nitrite
      towards the chloroplast is still largely unknown. All these fluxes are controlled
      by key factors, the 'major tour operators' like the internal nutritional status
      of the plant but also by external abiotic factors.

PMID- 21193581
TI  - Composition differences between epicuticular and intracuticular wax
      substructures: how do plants seal their epidermal surfaces?
AB  - The protective wax coating on plant surfaces has long been considered to be non
      uniform in composition at a subcellular scale. In recent years, direct evidence
      has started to accumulate showing quantitative compositional differences between
      the epicuticular wax (i.e. wax exterior to cutin that can be mechanically peeled
      off) and intracuticular wax (i.e. wax residing within the mechanically resistant
      layer of cutin) layers in particular. This review provides a first synthesis of
      the results acquired for all the species investigated to date in order to assign
      chemical information directly to cuticle substructures, together with an overview
      of the methods used and a discussion of possible mechanisms and biological
      functions. The development of methods to probe the wax for z-direction
      heterogeneity began with differential solvent extractions. Further research
      employing mechanical wax removal by adhesives permitted the separation and
      analysis of the epicuticular and intracuticular wax. In wild-type plants, the
      intracuticular (1-30 MUg cm(-2)) plus the epicuticular wax (5-30 MUg cm(-2))
      combined to a total of 8-40 MUg cm(-2). Cyclic wax constituents, such as
      triterpenoids and alkylresorcinols, preferentially or entirely accumulate within
      the intracuticular layer. Within the very-long-chain aliphatic wax components,
      primary alcohols tend to accumulate to higher percentages in the intracuticular
      wax layer, while free fatty acids and alkanes in many cases accumulate in the
      epicuticular layer. Compounds with different chain lengths are typically
      distributed evenly between the layers. The mechanism causing the fractionation
      remains to be elucidated but it seems plausible that it involves, at least in
      part, spontaneous partitioning due to the physico-chemical properties of the wax
      compounds and interactions with the intracuticular polymers. The arrangement of
      compounds probably directly influences cuticular functions.

PMID- 21193580
TI  - Mapping and linkage disequilibrium analysis with a genome-wide collection of SNPs
      that detect polymorphism in cultivated tomato.
AB  - The history of tomato (Solanum lycopersicum L.) improvement includes genetic
      bottlenecks, wild species introgressions, and divergence into distinct market
      classes. This history makes tomato an excellent model to investigate the effects
      of selection on genome variation. A combination of linkage mapping in two F(2)
      populations and physical mapping with emerging genome sequence data was used to
      position 434 PCR-based markers including SNPs. Three-hundred-and-forty markers
      were used to genotype 102 tomato lines representing wild species, landraces,
      vintage cultivars, and contemporary (fresh market and processing) varieties.
      Principal component analysis confirmed genetic divergence between market classes
      of cultivated tomato (P <0.0001). A genome-wide survey indicated that linkage
      disequilibrium (LD) decays over 6-8 cM when all cultivated tomatoes, including
      vintage and contemporary, were considered together. Within contemporary
      processing varieties, LD decayed over 6-14 cM, and decay was over 3-16 cM within
      fresh market varieties. Significant inter-chromosomal (gametic phase) LD was
      detected in both fresh market and processing varieties between chromosomes 2 and
      3, and 2 and 4, but in distinct chromosomal locations for each market class.
      Additional LD was detected between chromosomes 3 and 4, 3 and 11, and 4 and 6 in
      fresh market varieties and chromosomes 3 and 12 in processing varieties. These
      results suggest that breeding practices for market specialization in tomato have
      led to a genetic divergence between fresh market and processing types.

PMID- 21193582
TI  - Zinc isotopic fractionation in Phragmites australis in response to toxic levels
      of zinc.
AB  - Stable isotope signatures of Zn have shown great promise in elucidating changes
      in uptake and translocation mechanisms of this metal in plants during
      environmental changes. Here this potential was tested by investigating the effect
      of high Zn concentrations on the isotopic fractionation patterns of Phragmites
      australis (Cav.) Trin. ex Steud. Plants were grown for 40 d in a nutritive
      solution containing 3.2 MUM (sufficient) or 2 mM (toxic) Zn. The Zn isotopic
      composition of roots, rhizomes, shoots, and leaves was analysed. Stems and leaves
      were sampled at different heights to evaluate the effect of long-distance
      transport on Zn fractionation. During Zn sufficiency, roots, rhizomes, and shoots
      were isotopically heavy (delta(66)Zn(JMC Lyon)=0.20/00) while the youngest leaves
      were isotopically light (-0.50/00). During Zn excess, roots were still
      isotopically heavier (delta(66)Zn=0.50/00) and the rest of the plant was
      isotopically light (up to -0.50/00). The enrichment of heavy isotopes at the
      roots was attributed to Zn uptake mediated by transporter proteins under Zn
      sufficient conditions and to chelation and compartmentation in Zn excess. The
      isotopically lighter Zn in shoots and leaves is consistent with long-distance
      root to shoot transport. The tolerance response of P. australis increased the
      range of Zn fractionation within the plant and with respect to the environment.

PMID- 21193583
TI  - Cytochrome P-450 3A13 and endothelin jointly mediate ductus arteriosus
      constriction to oxygen in mice.
AB  - The fetal ductus arteriosus (DA) contracts to oxygen, and this feature, maturing
      through gestation, is considered important for its closure at birth. We have
      previously obtained evidence of the involvement of cytochrome P-450, possibly of
      the 3A subfamily (CYP3A), in oxygen sensing and have also identified endothelin
      (ET)-1 as the attendant effector for the contraction. Here, we examined
      comparatively wild-type (WT) and CYP3A-null (Cyp3a(-/-)) mice for direct
      validation of this concept. We found that the CYP3A subfamily is represented only
      by CYP3A13 in the WT DA. CYP3A13 was also detected in the DA by
      immunofluorescence microscopy, being primarily colocalized with the endoplasmic
      reticulum in both endothelial and muscle cells. However, a distinct signal was
      also evident in the plasma membrane. Isolated DAs from term WT animals developed
      a sustained contraction to oxygen with transient contractions superimposed.
      Conversely, no tonic response occurred in Cyp3a(-/-) DAs, whereas the phasic
      response persisted unabated. Oxygen did not contract the preterm WT DA but caused
      a full-fledged contraction after retinoic acid (RA) treatment. RA also promoted
      an oxygen contraction in the Cyp3a(-/-) DA. However, responses of RA-treated WT
      and Cyp3a(-/-) mice differed in that only the former abated with ET-1
      suppression. This implies the existence of an alternative target for RA
      responsible for the oxygen-induced contraction in the absence of CYP3A13. In
      vivo, the DA was constricted in WT and Cyp3a(-/-) newborns, although with a
      tendency to be less narrowed in the mutant. We conclude that oxygen acts
      primarily through the complex CYP3A13 (sensor)/ET-1 (effector) and, in an
      accessory way, directly onto ET-1. However, even in the absence of CYP3A13, the
      DA may close postnatally thanks to the contribution of ET-1 and the likely
      involvement of compensating mechanism(s) identifiable with an alternative oxygen
      sensing system and/or the withdrawal of relaxing influence(s) operating
      prenatally.

PMID- 21193585
TI  - Ion channelopathies: a tapped-out mine?

PMID- 21193584
TI  - Role of arachidonic acid lipoxygenase metabolites in acetylcholine-induced
      relaxations of mouse arteries.
AB  - Arachidonic acid (AA) metabolites function as EDHFs in arteries of many species.
      They mediate cyclooxygenase (COX)- and nitric oxide (NO)-independent relaxations
      to acetylcholine (ACh). However, the role of AA metabolites as relaxing factors
      in mouse arteries remains incompletely defined. ACh caused concentration
      dependent relaxations of the mouse thoracic and abdominal aorta and carotid,
      femoral, and mesentery arteries (maximal relaxation: 57 +/- 4%, 72 +/- 4%, 82 +/-
      3%, 80 +/- 3%, and 85 +/- 3%, respectively). The NO synthase inhibitor nitro-L
      arginine (L-NA; 30 MUM) blocked relaxations in the thoracic aorta, and L-NA plus
      the COX inhibitor indomethacin (10 MUM) inhibited relaxations in the abdominal
      aorta and carotid, femoral, and mesenteric arteries (maximal relaxation: 31 +/-
      10%, 33 +/- 5%, 41 +/- 8%, and 73 +/- 3%, respectively). In mesenteric arteries,
      NO- and COX-independent relaxations to ACh were inhibited by the lipoxygenase
      (LO) inhibitors nordihydroguaiaretic acid (NDGA; 10 MUM) and BW-755C (200 MUM),
      the K(+) channel inhibitor apamin (1 MUM), and 60 mM KCl and eliminated by
      endothelium removal. They were not altered by the cytochrome P-450 inhibitor N
      methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide (20 MUM) or the
      epoxyeicosatrienoic acid antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (10 MUM).
      AA relaxations were attenuated by NDGA or apamin and eliminated by 60 mM KCl.
      Reverse-phase HPLC analysis revealed arterial [(14)C]AA metabolites that
      comigrated with prostaglandins, trihydroxyeicosatrienoic acids (THETAs),
      hydroxyepoxyeicosatrienoic acids (HEETAs), and hydroxyeicosatetraenoic acids
      (HETEs). Epoxyeicosatrienoic acids were not observed. Mass spectrometry confirmed
      the identity of 6-keto-PGF(1alpha), PGE(2), 12-HETE, 15-HETE, HEETAs, 11,12,15
      THETA, and 11,14,15-THETA. AA metabolism was blocked by NDGA and endothelium
      removal. 11(R),12(S),15(S)-THETA relaxations (maximal relaxation: 73 +/- 3%) were
      endothelium independent and blocked by 60 mM KCl. Western immunoblot analysis and
      RT-PCR of the aorta and mesenteric arteries demonstrated protein and mRNA
      expression of leukocyte-type 12/15-LO. Thus, in mouse resistance arteries, 12/15
      LO AA metabolites mediate endothelium-dependent relaxations to ACh and AA.

PMID- 21193586
TI  - Decrease in the density of t-tubular L-type Ca2+ channel currents in failing
      ventricular myocytes.
AB  - In some forms of cardiac hypertrophy and failure, the gain of Ca(2+)-induced
      Ca(2+) release [CICR; i.e., the amount of Ca(2+) released from the sarcoplasmic
      reticulum normalized to Ca(2+) influx through L-type Ca(2+) channels (LTCCs)]
      decreases despite the normal whole cell LTCC current density, ryanodine receptor
      number, and sarcoplasmic reticulum Ca(2+) content. This decrease in CICR gain has
      been proposed to arise from a change in dyad architecture or derangement of the t
      tubular (TT) structure. However, the activity of surface sarcolemmal LTCCs has
      been reported to increase despite the unaltered whole cell LTCC current density
      in failing human ventricular myocytes, indicating that the "decreased CICR gain"
      may reflect a decrease in the TT LTCC current density in heart failure. Thus, we
      analyzed LTCC currents of failing ventricular myocytes of mice chronically
      treated with isoproterenol (Iso). Although Iso-treated mice exhibited intact t
      tubules and normal LTCC subunit expression, acute occlusion of t-tubules of
      isolated ventricular myocytes with osmotic shock (detubulation) revealed that the
      TT LTCC current density was halved in Iso-treated versus control myocytes.
      Pharmacological analysis indicated that kinases other than PKA or
      Ca(2+)/calmodulin-dependent protein kinase II insufficiently activated, whereas
      protein phosphatase 1/2A excessively suppressed, TT LTCCs in Iso-treated versus
      control myocytes. These results indicate that excessive beta-adrenergic
      stimulation causes the decrease in TT LTCC current density by altering the
      regulation of TT LTCCs by protein kinases and phosphatases in heart failure. This
      phenomenon might underlie the decreased CICR gain in heart failure.

PMID- 21193587
TI  - Regulation of in vivo cardiac contractility by phospholemman: role of Na+/Ca2+
      exchange.
AB  - Phospholemman (PLM), when phosphorylated at serine 68, relieves its inhibition on
      Na(+)-K(+)-ATPase but inhibits Na(+)/Ca(2+) exchanger 1 (NCX1) in cardiac
      myocytes. Under stress when catecholamine levels are high, enhanced Na(+)-K(+)
      ATPase activity by phosphorylated PLM attenuates intracellular Na(+)
      concentration ([Na(+)](i)) overload. To evaluate the effects of PLM on NCX1 on in
      vivo cardiac contractility, we injected recombinant adeno-associated virus
      (serotype 9) expressing either the phosphomimetic PLM S68E mutant or green
      fluorescent protein (GFP) directly into left ventricles (LVs) of PLM-knockout
      (KO) mice. Five weeks after virus injection, ~40% of isolated LV myocytes
      exhibited GFP fluorescence. Expression of S68E mutant was confirmed with PLM
      antibody. There were no differences in protein levels of alpha(1)- and alpha(2)
      subunits of Na(+)-K(+)-ATPase, NCX1, and sarco(endo)plasmic reticulum Ca(2+)
      ATPase between KO-GFP and KO-S68E LV homogenates. Compared with KO-GFP myocytes,
      Na(+)/Ca(2+) exchange current was suppressed, but resting [Na(+)](i), Na(+)-K(+)
      ATPase current, and action potential amplitudes were similar in KO-S68E myocytes.
      Resting membrane potential was slightly lower and action potential duration at
      90% repolarization (APD(90)) was shortened in KO-S68E myocytes. Isoproterenol
      (Iso; 1 MUM) increased APD(90) in both groups of myocytes. After Iso, [Na(+)](i)
      increased monotonically in paced (2 Hz) KO-GFP but reached a plateau in KO-S68E
      myocytes. Both systolic and diastolic [Ca(2+)](i) were higher in Iso-stimulated
      KO-S68E myocytes paced at 2 Hz. Echocardiography demonstrated similar resting
      heart rate, ejection fraction, and LV mass between KO-GFP and KO-S68E mice. In
      vivo closed-chest catheterization demonstrated enhanced contractility in KO-S68E
      compared with KO-GFP hearts stimulated with Iso. We conclude that under
      catecholamine stress when [Na(+)](i) is high, PLM minimizes [Na(+)](i) overload
      by relieving its inhibition of Na(+)-K(+)-ATPase and preserves inotropy by
      simultaneously inhibiting Na(+)/Ca(2+) exchanger.

PMID- 21193588
TI  - Differential contribution of mitochondria, NADPH oxidases, and glycolysis to
      region-specific oxidant stress in the anoxic-reoxygenated embryonic heart.
AB  - The ability of the developing myocardium to tolerate oxidative stress during
      early gestation is an important issue with regard to possible detrimental
      consequences for the fetus. In the embryonic heart, antioxidant defences are low,
      whereas glycolytic flux is high. The pro- and antioxidant mechanisms and their
      dependency on glucose metabolism remain to be explored. Isolated hearts of 4-day
      old chick embryos were exposed to normoxia (30 min), anoxia (30 min), and
      hyperoxic reoxygenation (60 min). The time course of ROS production in the whole
      heart and in the atria, ventricle, and outflow tract was established using
      lucigenin-enhanced chemiluminescence. Cardiac rhythm, conduction, and arrhythmias
      were determined. The activity of superoxide dismutase, catalase, gutathione
      reductase, and glutathione peroxidase as well as the content of reduced and
      oxidized glutathione were measured. The relative contribution of the ROS
      generating systems was assessed by inhibition of mitochondrial complexes I and
      III (rotenone and myxothiazol), NADPH oxidases (diphenylene iodonium and
      apocynine), and nitric oxide synthases (N-monomethyl-L-arginine and N-iminoethyl
      L-ornithine). The effects of glycolysis inhibition (iodoacetate), glucose
      deprivation, glycogen depletion, and lactate accumulation were also investigated.
      In untreated hearts, ROS production peaked at 10.8 +/- 3.3, 9 +/- 0.8, and 4.8 +/
      0.4 min (means +/- SD; n = 4) of reoxygenation in the atria, ventricle, and
      outflow tract, respectively, and was associated with arrhythmias. Functional
      recovery was complete after 30-40 min. At reoxygenation, 1) the respiratory chain
      and NADPH oxidases were the main sources of ROS in the atria and outflow tract,
      respectively; 2) glucose deprivation decreased, whereas glycogen depletion
      increased, oxidative stress; 3) lactate worsened oxidant stress via NADPH oxidase
      activation; 4) glycolysis blockade enhanced ROS production; 5) no nitrosative
      stress was detectable; and 6) the glutathione redox cycle appeared to be a major
      antioxidant system. Thus, the glycolytic pathway plays a predominant role in
      reoxygenation-induced oxidative stress during early cardiogenesis. The relative
      contribution of mitochondria and extramitochondrial systems to ROS generation
      varies from one region to another and throughout reoxygenation.

PMID- 21193589
TI  - iNOS expression in vascular resident macrophages contributes to circulatory
      dysfunction of splanchnic vascular smooth muscle contractions in portal
      hypertensive rats.
AB  - Portal hypertension, a major complication of cirrhosis, is caused by both
      increased portal blood flow due to arterial vasodilation and augmented
      intrahepatic vascular resistance due to sinusoidal constriction. In this study,
      we examined the possible involvement of resident macrophages in the tone
      regulation of splanchnic blood vessels using bile duct ligated (BDL) portal
      hypertensive rats and an in vitro organ culture method. In BDL cirrhosis, the
      number of ED2-positive resident macrophages increased by two- to fourfold in the
      vascular walls of the mesenteric artery and extrahepatic portal vein compared
      with those in sham-operated rats. Many ED1-positive monocytes were also recruited
      into this area. The expression of inducible nitric oxide (NO) synthase (iNOS)
      mRNA was increased in the vascular tissues isolated from BDL rats, and
      accordingly, nitrate/nitrite production was increased. Immunohistochemistry
      revealed that iNOS was largely expressed in ED1-positive and ED2-positive cells.
      We further analyzed the effect of iNOS expression on vascular smooth muscle
      contraction using an in vitro organ culture system. iNOS mRNA expression and
      nitrate production significantly increased in vascular tissues (without
      endothelium) incubated with 1 MUg/ml lipopolysaccharide (LPS) for 6 h.
      Immunohistochemistry indicated that iNOS was largely expressed in ED2-positive
      resident macrophages. alpha-Adrenergic-stimulated contractility of the mesenteric
      artery was greatly suppressed by LPS treatment and was restored by N(G)-nitro-L
      arginine methyl ester (NO synthase inhibitor); in contrast, portal vein
      contractility was largely unaffected by LPS. Sodium nitroprusside (NO donor) and
      8-bromo-cGMP showed greater contractile inhibition in the mesenteric artery than
      in the portal vein with decreasing myosin light chain phosphorylation. In the
      presence of an alpha-adrenergic agonist, the mesenteric artery cytosolic Ca(2+)
      level was greatly reduced by sodium nitroprusside; however, the portal vein
      Ca(2+) level was largely unaffected. These results suggest that the induction of
      iNOS in monocytes/macrophages contributes to a hypercirculatory state in the
      cirrhosis model rat in which the imbalance of the responsiveness of visceral
      vascular walls to NO (mesenteric artery >> portal vein) may account for the
      increased portal venous flow in portal hypertension.

PMID- 21193590
TI  - Lack of microsomal prostaglandin E synthase-1 reduces cardiac function following
      angiotensin II infusion.
AB  - Our laboratory previously reported that inducible PGE(2) synthase, mPGES-1,
      contributes to micromolar production of PGE(2) in neonatal ventricular myocytes
      in vitro, which stimulates their growth. We therefore hypothesized that mPGES-1
      contributes to cardiac hypertrophy following angiotensin II (ANG II) infusion. To
      test this hypothesis, we used 10- to 12-wk-old mPGES-1 knockout mice (mPGES-1 KO)
      and C57Bl/6 control mice infused for 8 wk with either 1.4 mg . kg(-1) . day(-1)
      ANG II or vehicle subcutaneously. Blood pressure [systolic blood pressure (SBP)]
      was measured throughout the study, and cardiac function was assessed by M-mode
      echocardiography at baseline and at 8 wk of infusion. At the conclusion of the
      study, immunohistochemistry was used to evaluate collagen fraction, myocyte cross
      sectional area (MCSA), and apoptosis. At baseline, there was no difference in SBP
      between mPGES-1 KO mice and C57BL/6 controls. ANG II infusion increased SBP to
      similar levels in both strains. In control mice, infusion of ANG II increased
      MCSA and posterior wall thickness at diastole (PWTd) but had little effect on
      cardiac function, consistent with compensatory hypertrophy. In contrast, cardiac
      function was worse in mPGES-1 KO mice after ANG II treatment. Ejection fraction
      declined from 76.2 +/- 2.7 to 63.3 +/- 3.4% after ANG II, and left ventricular
      dimension at systole and diastole increased from 1.29 +/- 0.02 to 1.78 +/- 0.15
      mm and from 2.57 +/- 0.03 to 2.90 +/- 0.13 mm, respectively. Infusion of ANG II
      increased both the LV-to-body weight and the mass-to-body weight ratios to a
      similar extent in both strains. However, PWTd increased by a lesser extent in KO
      mice, suggesting an impaired hypertrophic response. ANG II infusion increased
      collagen staining similarly in both strains, but TdT-dUTP nick end labeling
      staining was greater in mPGES-1 KO mice. Overall, these results are consistent
      with a beneficial effect for mPGES-1 in the maintenance of cardiac function in
      ANG II-dependent hypertension.

PMID- 21193591
TI  - Orthopaedic in-training examination: an analysis of the sports medicine section.
AB  - BACKGROUND: Since 1963, the Orthopaedic In-Training Examination (OITE) has been
      administered to orthopaedic residents to assess resident knowledge and measure
      the quality of teaching within individual programs. The OITE has evolved
      dramatically over the years and now maintains a standardized format consisting of
      275 questions divided among 12 sections. PURPOSE: To provide a detailed analysis
      of the OITE sports medicine section to identify patterns in question content,
      recommended references, and resident performance. STUDY DESIGN: Cross-sectional
      study. METHODS: All OITE sports medicine questions from 2005 to 2009 were
      analyzed, and the following data were recorded: resident performance scores,
      tested topics, type of imaging modalities, tested treatment modalities, taxonomy
      classification, and recommended references. RESULTS: From 2005 to 2009, the
      sports medicine section composed 7.8% of the OITE. Mean resident performance on
      the entire OITE as well as on the sports medicine section improved during each
      year of training. Imaging modalities typically involved questions on radiographs
      and magnetic resonance imaging and constituted 27.4% of the OITE sports medicine
      section. Treatment modalities involved 36.8% of the OITE sports medicine section
      questions, including most treatment questions relating to ligament reconstruction
      or rehabilitation. The authors' assessment of taxonomy classification showed that
      recall-type questions were most common; however, mean resident performance was
      minimally affected by type of taxonomy question. Finally, there were trends noted
      in recommended references; namely, the American Journal of Sports Medicine and
      Orthopaedic Knowledge Update Sports Medicine were the most commonly and
      consistently cited journal and review book, respectively. CONCLUSION: The current
      study provides some unique information relating to content, recommended
      references, and resident performance on the OITE sports medicine section. It is
      hoped this information will provide orthopaedic trainees, orthopaedic residency
      programs, and the American Academy of Orthopaedic Surgeons Evaluation Committee
      valuable information relating to improving resident knowledge and performance and
      optimizing sports medicine educational curricula.

PMID- 21193592
TI  - Remodeling of articular cartilage and subchondral bone after bone grafting and
      matrix-associated autologous chondrocyte implantation for osteochondritis
      dissecans of the knee.
AB  - BACKGROUND: Osteochondritis dissecans (OCD) of the knee is a challenging problem.
      Previously, the authors implemented a novel 1-step surgical procedure for OCD
      treatment consisting of matrix-associated autologous chondrocyte implantation
      (ACI) and simultaneous bone reconstruction including the subchondral lamina.
      PURPOSE: This study presents the 2-to 5-year results after this technique,
      assessing correlations of clinical function and cartilage and bone remodeling
      processes. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Twenty-six
      patients with symptomatic condylar knee OCD (International Cartilage Repair
      Society OCD III/IV) were treated with matrix-associated ACI and monocortical
      cancellous cylinders for defect filling and subchondral bone plate reconstruction
      using cortical graft layers as novel subchondral lamina. Evaluations were
      performed with clinical rating scales and 1.5-T magnetic resonance imaging using
      the magnetic resonance observation of cartilage repair tissue (MOCART) score and
      a newly implemented subchondral lamina remodeling grade. RESULTS: The defect size
      was 5.3 +/- 2.3 cm(2). The defect depth was 8.7 +/- 2.4 mm. After a follow-up of
      39.8 +/- 12.0 months, all scores improved significantly. Nineteen patients (73%)
      reached good/excellent results in the Lysholm-Gillquist score (preoperatively:
      53.2 +/- 18.0 points; latest follow-up: 88.5 +/- 9.5 points) and the Cincinnati
      knee rating score (preoperatively: 51.7 +/- 13.0 points; latest follow-up: 84.6
      +/- 11.7 points) and significant improvements in the subjective International
      Knee Documentation Committee (IKDC) score by 27.9% (preoperatively: 50.5% +/-
      16.1%; latest follow-up: 78.4% +/- 13.4%). The MOCART score reached 62.4 +/- 18.9
      points. The clinical improvement and tissue remodeling occurred simultaneously
      and timed; thus, the cartilage defect filling and the lamina remodeling grades
      correlated significantly with each other, the follow-up time, and almost all
      clinical scores. CONCLUSION: The simultaneous reconstruction of deep
      osteochondral defects of the knee OCD with monocortical cancellous cylinders and
      matrix-associated ACI is a biological, 1-step alternative to osteochondral
      cylinder transfer or conventional ACI that leads to good clinical and magnetic
      resonance imaging results after an intermediate follow-up period. The present
      study demonstrated simultaneous remodeling processes of articular cartilage
      repair tissue and subchondral lamina; this synchronization is not yet understood
      and deserves further investigation.

PMID- 21193593
TI  - Critically evaluating the role of diagnostic imaging in osteomyelitis.
AB  - Early diagnosis, essential for timely appropriate treatment and reduction of
      complications, can be difficult. This article aims to give an overview of the
      role that different imaging modalities have to play in the diagnosis of
      osteomyelitis. Osteomyelitis is a heterogeneous disease in its pathophysiology,
      clinical presentation, and management. It infers inflammation of bone and marrow,
      whereas osteitis is inflammation of the bone only. Thus, a soft-tissue infection
      that reaches the bone surface but has not infected the marrow is osteitis and not
      osteomyelitis. Chronic osteomyelitis is divided into active and inactive forms.
      Newly appearing periosteal reaction or bone destruction within the chronic
      involucrum are indicators of activation. Imaging modalities represent different
      underlying pathophysiological processes that may be represented in differing
      types and differing phases of osteomyelitis. Sequential selection of appropriate
      imaging modalities requires a thorough understanding of the disease processes and
      the process by which each modality visualizes this dynamic disease process.

PMID- 21193594
TI  - Salvage of severe ankle varus deformity with soft tissue and bone rebalancing.
AB  - The etiology of ankle varus is multifactorial. Treatment recommendations after
      failed conservative care include hindfoot and ankle fusions or total ankle
      arthroplasty (TAA) with ligament rebalancing. The purpose of this study was to
      evaluate chronic varus ankle deformities through corrective calcaneal osteotomies
      and lateral soft tissue reconstruction. All skeletally mature patients with at
      least 5 degrees of ankle varus were included in the study. Pre and postoperative
      radiographs were retrospectively reviewed measuring talar tilt. All patients had
      a lateral closing wedge (Dwyer) calcaneal osteotomy, joint debridement, and
      lateral ankle ligament reconstruction. Eight feet were included in the study. The
      average follow-up time was 20.6 months. Six patients (six feet) were asymptomatic
      and did not have any additional surgery at their most recent follow-up. Two
      patients failed treatment, requiring surgical intervention for persistent pain
      and/or deformity. The average postoperative ankle varus correction overall was
      4.9 degrees. We found ankle varus on average of less than 10 degrees can be
      reliably corrected with a combination of lateral ligament reconstruction and
      calcaneal osteotomy. Approximately 50% of the deformity was corrected when
      comparing pre and postoperative talar tilt values. In patients with varus
      deformity greater than 10 degrees preoperatively, persistent varus may occur.

PMID- 21193595
TI  - The impact of the Flynn effect on LD diagnoses in special education.
AB  - Because of the Flynn effect, IQ scores rise as a test norm ages but drop on the
      introduction of a newly revised test norm. The purpose of the current study was
      to determine the impact of the Flynn effect on learning disability (LD)
      diagnoses, the most prevalent special education diagnosis in the United States.
      Using a longitudinal sample of 875 school children who were initially diagnosed
      with LD on the Wechsler Intelligence Scale for Children-Revised (WISC-R),
      children experienced a significant decline in IQ when retested on the third
      edition of the WISC (WISC-III) compared to peers who were tested on the WISC-R
      twice. Furthermore, results from logistic regression analyses revealed that the
      probability of a rediagnosis of LD on reevaluation significantly decreased, in
      part, because of this decline on the WISC-III. These results are discussed in
      terms of their implications for both basic research and educational policy.

PMID- 21193596
TI  - Characterization of complex adnexal masses: value of adding perfusion- and
      diffusion-weighted MR imaging to conventional MR imaging.
AB  - PURPOSE: To retrospectively determine the value of adding perfusion-weighted (PW)
      and diffusion-weighted (DW) sequences to a conventional magnetic resonance (MR)
      imaging protocol to differentiate benign from malignant tumors. MATERIALS AND
      METHODS: The institutional ethics committee approved this retrospective study and
      waived the requirement to obtain informed consent. MR images in 87 women (age
      range, 25-87 years) who underwent imaging before surgery for complex adnexal
      masses-excluding endometriomas and cystic teratomas-were analyzed. Conventional
      morphologic, perfusion, and diffusion MR criteria of malignancy were recorded.
      Three independent observers reviewed images in four steps: conventional MR images
      alone, conventional MR images and PW images combined, conventional MR images and
      DW images combined, and conventional, PW, and DW MR images combined. Receiver
      operating characteristic curve analysis was performed to compare the results of
      the readings. A recursive partitioning model was built to establish a
      multivariate decision tree. RESULTS: There was almost perfect agreement for
      lesion characterization regardless of the reader experiment or step considered
      (kappa = 0.811-0.929). Area under the receiver operating characteristic curve
      values were higher for conventional and DW images combined, conventional and PW
      images combined, and conventional, DW, and PW images combined compared with
      conventional MR images alone (P < .05). For all readers, the accuracy of
      conventional, PW, and DW imaging combined was higher than that of conventional MR
      imaging alone for benign masses (P < .01) but not for malignant masses (P = .24).
      The addition of both PW and DW images led to a correct change in the diagnosis in
      19% (11 of 57 patients), 23% (13 of 57 patients), and 24% (14 of 57 patients) of
      cases for readers 1, 2, and 3, respectively, with no incorrect changes.
      Conventional, PW, and DW MR imaging criteria were combined to generate a decision
      tree giving an accuracy of 95%. CONCLUSION: The addition of PW and DW sequences
      to a conventional MR imaging protocol improved the diagnostic accuracy in the
      characterization of complex adnexal masses.

PMID- 21193597
TI  - Gastrointestinal stromal tumors treated with imatinib mesylate: apparent
      diffusion coefficient in the evaluation of therapy response in patients.
AB  - PURPOSE: To prospectively investigate the use of the apparent diffusion
      coefficient (ADC) as an early response indicator in patients with
      gastrointestinal stromal tumors (GISTs) treated with imatinib mesylate. MATERIALS
      AND METHODS: This study was approved by the institutional review board and
      written informed consent was obtained from all patients. Diffusion-weighted
      magnetic resonance (MR) imaging was performed in 32 patients with GISTs before
      and 1, 4, and 12 weeks after treatment with a tyrosine kinase inhibitor, imatinib
      mesylate. The measurable lesions were classified as having responded well or
      poorly according to size alterations at clinical evaluation following the first
      round of treatment (3 months). A linear mixed-effects model was applied to
      analyze changes in the ADCs of tumors during treatment and to compare the
      variation and slopes of the time-dependent ADC curves between the good- and poor
      response groups. RESULTS: There were 56 lesions in the good-response group and 35
      in the poor-response group. An early (1 week after therapy) noticeable and
      statistically significant (P < .001) increase in the ADC was observed in the good
      response group (median ADC increase, 44.8%) but not in the poor-response group
      (median ADC increase, 1.5%). The time-dependent ADC variation was significantly
      different between the good- and poor-response groups, with a sharper median ADC
      increase displayed in the former (week 1: 44.8% vs 1.5%; week 4: 80.4% vs 7.8%;
      week 12: 89.6% vs 16.7%; F = 25.78, P < .001). The largest difference in the
      weekly percentage increase in ADC between the good- and poor-response groups was
      observed at 1 week after therapy (week 0-1: 44.8% vs 1.5%; week 1-4: 7.0% vs
      2.8%; week 4-12: 1.6% vs 0.7%). The pretherapy mean ADC (+/- standard deviation)
      of lesions in the good-response group (1.06 [*10(-3) mm(2)/sec] +/- 0.27) was
      significantly lower than that in the poor-response group (1.24 [*10(-3)
      mm(2)/sec] +/- 0.32) (F = 8.34, P = .005). CONCLUSION: Comparatively low
      pretherapy ADC and marked ADC increase at 1 week after therapy is associated with
      good response to imatinib mesylate in patients with GISTs.

PMID- 21193598
TI  - Pleural effusion detected at CT prior to primary cytoreduction for stage III or
      IV ovarian carcinoma: effect on survival.
AB  - PURPOSE: To determine the prognostic importance of pleural effusions on
      preoperative computed tomographic (CT) images in patients with advanced
      epithelial ovarian cancer. MATERIALS AND METHODS: The institutional review board
      waived informed consent for this HIPAA-compliant study of 203 patients with
      International Federation of Obstetrics and Gynecology stage III (n = 172) or IV
      (n = 31) epithelial ovarian cancer who underwent CT before primary cytoreductive
      surgery between 1997 and 2004 (mean age, 61 years; range, 37-96 years). Two
      radiologists retrospectively evaluated chest and/or abdominal CT images for
      pleural malignancy and the presence, size, and laterality of pleural effusions.
      To evaluate survival, Kaplan-Meier methods were used, with log-rank P values for
      comparisons. Multivariate analyses were conducted by using Cox proportional
      hazards regression. kappa Statistics were calculated for interreader agreement.
      RESULTS: Median survival was 50 months (95% confidence interval [CI]: 45, 55
      months) for patients with stage III disease and 41 months (95% CI: 27, 58 months)
      for patients with stage IV disease. Readers 1 and 2 found pleural effusions in 40
      and 41 stage III and 20 and 21 stage IV patients, respectively. At multivariate
      analysis, after controlling for stage, age at surgery, preoperative serum CA-125
      level, debulking status, and ascites, moderate-to-large pleural effusion on CT
      images was significantly associated with worse overall survival (reader 1: hazard
      ratio = 2.27 [95% CI: 1.31, 3.92], P < .01; reader 2: hazard ratio = 2.25 [95%
      CI: 1.26, 4.01], P = .02). Preoperative CA-125 level, debulking status, and
      ascites were also significant survival predictors (P <= .03 for all for both
      readers). Readers agreed substantially in distinguishing small from moderate-to
      large effusions (kappa = 0.764). CONCLUSION: Moderate-to-large pleural effusion
      on preoperative CT images in patients with stage III or IV epithelial ovarian
      cancer was independently associated with poorer overall survival after
      controlling for age, preoperative CA-125 level, surgical stage, ascites, and
      cytoreductive status.

PMID- 21193599
TI  - The family Agaricaceae: phylogenies and two new white-spored genera.
AB  - A well resolved phylogeny of the Agaricaceae based on partial rpb2 sequences is
      presented from a wide geographic and systematic sampling of the family and
      compared to phylogenies based on nrLSU and tef1 sequences. A smaller dataset of
      the family focusing on the Agaricus clade of nrITS sequences and a combined
      dataset were used to determine the position of several white-spored taxa from
      northern Thailand. Two new genera are described from Thailand. Coniolepiota
      accommodates Lepiota spongodes, a gray-lilac-purple floccose white-spored species
      with a wide distribution in tropical Asia; Eriocybe has a white wooly felt-like
      covering of pileus and stipe, white spores and is described with one new species
      E. chionea, so far known only from northern Thailand. These new genera are
      closely related to three genera with colored spores (viz. Agaricus,
      Heinemannomyces and Clarkeinda) and not to other white-spored taxa.

PMID- 21193600
TI  - Morphological and molecular characterization of Phytophthora glovera sp. nov.
      from tobacco in Brazil.
AB  - A root rot disease of cultivated tobacco called yellow stunt has been observed in
      the burley tobacco production areas of Brazil since the early 1990s. Root
      infecting fungi and straminipiles were isolated from the roots of diseased
      tobacco plants, including a semi-papillate, homothallic, slow growing
      Phytophthora species. Pathogenicity trials confirmed that Phytophthora sp. caused
      root rot and stunting of burley and flue-cured tobaccos. Morphological
      characteristics of the asexual and sexual stages of this organism did not match
      any reported Phytophthora species and were very different from the widely known
      tobacco black shank pathogen P. nicotianae. Phylogenetic analysis based on
      sequences of the internal transcribed spacer rDNA, beta-tubulin and translation
      elongation factor 1-alpha regions indicated that this organism represents a
      previously unreported Phytophthora species that is significantly supported in
      clade 2 and most closely related to P. capsici. However P. glovera differs from
      P. capsici in a number of morphological characters, most significantly P. glovera
      is homothallic and produces both paragynous and amphigynous antheridia while P.
      capsici is heterothallic and produces only amphigynous antheridia. In this paper
      we confirmed pathogenicity of this species on tobacco and describe the
      morphological and molecular characteristics of Phytophthora glovera sp. nov.

PMID- 21193601
TI  - Taxonomy of Pluteus eugraptus and morphologically similar taxa.
AB  - The status of the taxa morphologically similar to Pluteus eugraptus
      (Basidiomycota, Agaricales) was investigated with morphological and molecular
      (ITS region) characters. This group of species belongs in Pluteus sect.
      Celluloderma based on morphological and molecular characters. Two species,
      Pluteus multiformis, from Spain and Pluteus eludens from Madeira, Portugal,
      Russia and USA, are described as new. Both species share pigmented cheilocystidia
      and a pileipellis composed of both clavate-spheropedunculate and elongated
      elements with P. eugraptus, but they can be separated based on the
      characteristics of the cystidia and pileipellis. Pluteus multiformis is
      characterized by the scarce pleurocystidia, clavate cheilocystidia and
      caulocystidia and highly polymorphic elements of the pileipellis. Pluteus eludens
      is characterized mainly by utriform pleurocystidia. Pluteus eugraptus is known
      only with certainty from the type collection (Sri Lanka), which has been re
      examined here, and it is characterized by narrowly lageniform pleurocystidia.
      Phylogenetic analyses based on ITS region sequence data supported the separation
      of P. multiformis, P. eludens and an additional collection from Japan that likely
      represents the true P. eugraptus.

PMID- 21193602
TI  - Expression of genes of Rhizoctonia solani and the biocontrol Stachybotrys elegans
      during mycoparasitism of hyphae and sclerotia.
AB  - Knowledge of mycoparasitism has been focused on how antagonists affect pathogens
      in relation to mechanisms, metabolites and gene expression. Just as microbial
      antagonists use a diverse arsenal of mechanisms to dominate interactions with
      hosts, hosts also have diverse responses to counteract antagonism. In this study
      differential gene expression of eight mycoparasitism-induced genes and eight host
      response genes was monitored during in vivo interactions between the mycoparasite
      Stachybotrys elegans and hyphae and sclerotia of the host, Rhizoctonia solani
      over 5 d of interaction. Using real time reverse transcription polymerase chain
      reaction, comparative analyses demonstrated that hyphal and sclerotial structures
      triggered different expression patterns. These results indicated that multiple
      regulatory mechanisms might be involved. The high elevated expression of some
      genes belonging to the mycoparasite and the host suggest that these genes play an
      important role during the mycoparasitic process and host defense respectively.

PMID- 21193604
TI  - Replisome trafficking in growing vegetative hyphae of Streptomyces coelicolor
      A3(2).
AB  - We observed movies of replisome trafficking during Streptomyces coelicolor
      growth. A replisome(s) in the spore served as a replication center(s) until
      hyphae reached a certain length, when a tip-proximal replisome formed and moved
      at a fixed distance behind the tip at a speed equivalent to the extension rate of
      the tip.

PMID- 21193603
TI  - A new lichenicolous teleomorph is related to plant pathogens in Laetisaria and
      Limonomyces (Basidiomycota, Corticiales).
AB  - Molecular and morphological data were used to assess the taxonomic placement of
      an undescribed lichenicolous basidiomycete teleomorph collected in Luxembourg,
      Belgium and Germany. The new species is ecologically and morphologically similar
      to Marchandiobasidium aurantiacum, teleomorph of the common bulbilliferous lichen
      pathogen Marchandiomyces aurantiacus. However phylogenetic analysis of nuclear
      and mitochondrial rDNA sequences indicated a close relationship of the new
      species-not to M. aurantiacum but to turf grass pathogens in genera Laetisaria
      and Limonomyces, including the generic type of Laetisaria. We are including the
      new species in Laetisaria based on strong statistical support for the clade
      containing these teleomorphs and several Marchandiomyces anamorphs. The
      morphological and ecological diversity of this clade indicates a potentially
      significant evolutionary role played by lichen-associated species in the
      Corticiales.

PMID- 21193605
TI  - Regulation of central metabolism genes of Mycobacterium tuberculosis by parallel
      feed-forward loops controlled by sigma factor E (sigma(E)).
AB  - Cells respond to external stimuli through networks of regulatory interactions.
      The human pathogen Mycobacterium tuberculosis responds to stress encountered
      during infection by arresting multiplication and implementing critical metabolic
      changes that lead to or sustain the nonreplicative state. Much of this
      differentiation program is recapitulated when M. tuberculosis cultures are
      subjected to gradual oxygen depletion in vitro. Here we report that hypoxic
      induction of critical central metabolism genes in the glyoxylate shunt (icl1) and
      in the methylcitrate cycle (gltA1) involves both global and local regulators. The
      global regulators are accessory sigma factors sigma(B) for icl1 and sigma(E) for
      gltA1. The local regulators are the products of two paralogous genes mapping at
      positions adjacent to the corresponding effector gene or operon. We call these
      genes lrpI and lrpG (for local regulatory protein of icl1 and gltA1). We also
      found that (i) each sigma factor controls the corresponding local regulator, (ii)
      both global and local regulators are required for effector gene induction, and
      (iii) the occurrence of sigma factor control of effector gene induction is
      independent of its control over the corresponding local regulator. Together,
      these data indicate that induction of icl1 and gltA1 utilizes parallel feed
      forward loops with an AND input function. Both feed-forward loops are affected by
      sigma(E), since this sigma factor is part of the gltA1 loop and controls sigB in
      the icl1 loop. Feed-forward loops may critically contribute to the cellular
      developmental program associated with M. tuberculosis dormancy.

PMID- 21193607
TI  - Regulation of acid resistance by connectors of two-component signal transduction
      systems in Escherichia coli.
AB  - Two-component signal transduction systems (TCSs), utilized extensively by
      bacteria and archaea, are involved in the rapid adaptation of the organisms to
      fluctuating environments. A typical TCS transduces the signal by a phosphorelay
      between the sensor histidine kinase and its cognate response regulator. Recently,
      small-sized proteins that link TCSs have been reported and are called
      "connectors." Their physiological roles, however, have remained elusive. SafA
      (sensor associating factor A) (formerly B1500), a small (65-amino-acid [65-aa])
      membrane protein, is among such connectors and links Escherichia coli TCSs
      EvgS/EvgA and PhoQ/PhoP. Since the activation of the EvgS/EvgA system induces
      acid resistance, we examined whether the SafA-activated PhoQ/PhoP system is also
      involved in the acid resistance induced by EvgS/EvgA. Using a constitutively
      active evgS1 mutant for the activation of EvgS/EvgA, we found that SafA, PhoQ,
      and PhoP all contributed to the acid resistance phenotype. Moreover, EvgS/EvgA
      activation resulted in the accumulation of cellular RpoS in the exponential-phase
      cells in a SafA-, PhoQ-, and PhoP-dependent manner. This RpoS accumulation was
      caused by another connector, IraM, expression of which was induced by the
      activation of the PhoQ/PhoP system, thus preventing RpoS degradation by trapping
      response regulator RssB. Acid resistance assays demonstrated that IraM also
      participated in the EvgS/EvgA-induced acid resistance. Therefore, we propose a
      model of a signal transduction cascade proceeding from EvgS/EvgA to PhoQ/PhoP and
      then to RssB (connected by SafA and IraM) and discuss its contribution to the
      acid resistance phenotype.

PMID- 21193606
TI  - Upregulation of MetC is essential for D-alanine-independent growth of an alr/dadX
      deficient Escherichia coli strain.
AB  - D-Alanine is a central component of the cell wall in most prokaryotes. D-Alanine
      synthesis in Escherichia coli is carried out by two different alanine racemases
      encoded by the alr and dadX genes. Deletion of alr and dadX from the E. coli
      genome results in a D-alanine auxotrophic phenotype. However, we have observed
      growth of prototrophic phenotypic revertants during routine culturing of a D
      alanine auxotrophic strain. We present a detailed comparison of the proteome and
      transcriptome profiles of the D-alanine auxotroph and a prototrophic revertant
      strain. Most noticeably, a general upregulation of genes involved in methionine
      synthesis in the revertant strain was detected. The appearance of the revertant
      phenotype was genetically linked to point mutations in the methionine repressor
      gene (metJ). Our results reveal an alternative metabolic pathway which can supply
      essential d-alanine for peptidoglycan synthesis of alr- and dadX-deficient E.
      coli mutants and provide evidence for significant alanine racemase coactivity of
      the E. coli cystathionine beta-lyase (MetC).

PMID- 21193608
TI  - Specific role of the cyanobacterial PipX factor in the heterocysts of Anabaena
      sp. strain PCC 7120.
AB  - The PipX factor is a regulatory protein that seems to occur only in
      cyanobacteria. In the filamentous, heterocyst-forming Anabaena sp. strain PCC
      7120, open reading frame (ORF) asr0485, identified as the pipX gene, is expressed
      mainly under conditions of combined-nitrogen deprivation dependent on the global
      N regulator NtcA and the heterocyst-specific regulator HetR. Primer extension and
      5' rapid amplification of cDNA ends (RACE) analyses detected three transcription
      start points corresponding to a canonical NtcA-activated promoter (to which
      direct binding of NtcA was observed), an NtcA- and HetR-dependent promoter, and a
      consensus-type promoter, the last with putative -35 and -10 determinants.
      Activation of pipX took place in cells differentiating into heterocysts at
      intermediate to late stages of the process. Accordingly, disruption of pipX led
      to impaired diazotrophic growth, reduced nitrogenase activity, and impaired
      activation of the nitrogenase structural genes. The nitrogenase activity of the
      mutant was low under oxic conditions, likely resulting from inefficient
      protection against oxygen. In line with this, the activation of the coxB2A2C2 and
      coxB3A3C3 operons, encoding heterocyst-specific terminal respiratory oxidases
      responsible for internal oxygen removal, was deficient in the pipX mutant.
      Therefore, the Anabaena PipX factor shows a spatiotemporal specificity
      contributing to normal heterocyst function, including full activation of the
      nitrogenase structural genes and genes of the nitrogenase-protective features of
      the heterocyst.

PMID- 21193609
TI  - Defining the plasmid-borne restriction-modification systems of the Lyme disease
      spirochete Borrelia burgdorferi.
AB  - The restriction-modification (R-M) systems of many bacteria present a barrier to
      the stable introduction of foreign DNA. The Lyme disease spirochete Borrelia
      burgdorferi has two plasmid-borne putative R-M genes, bbe02 and bbq67, whose
      presence limits transformation by shuttle vector DNA from Escherichia coli. We
      show that both the bbe02 and bbq67 loci in recipient B. burgdorferi limit
      transformation with shuttle vector DNA from E. coli, irrespective of its dam,
      dcm, or hsd methylation status. However, plasmid DNA purified from B. burgdorferi
      transformed naive B. burgdorferi much more efficiently than plasmid DNA from E.
      coli, particularly when the bbe02 and bbq67 genotypes of the B. burgdorferi DNA
      source matched those of the recipient. We detected adenine methylation of plasmid
      DNA prepared from B. burgdorferi that carried bbe02 and bbq67. These results
      indicate that the bbe02 and bbq67 loci of B. burgdorferi encode distinct R-M
      enzymes that methylate endogenous DNA and cleave foreign DNA lacking the same
      sequence-specific modification. Our findings have basic implications for
      horizontal gene transfer among B. burgdorferi strains with distinct plasmid
      contents. Further characterization and identification of the nucleotide sequences
      recognized by BBE02 and BBQ67 will facilitate efficient genetic manipulation of
      this pathogenic spirochete.

PMID- 21193610
TI  - Phenotypic and genotypic evidence for L-fucose utilization by Campylobacter
      jejuni.
AB  - Campylobacter jejuni remains among the leading causes of bacterial food-borne
      illness. The current understanding of Campylobacter physiology suggests that it
      is asaccharolytic and is unable to catabolize exogenous carbohydrates. Contrary
      to this paradigm, we provide evidence for l-fucose utilization by C. jejuni. The
      fucose phenotype, shown in chemically defined medium, is strain specific and
      linked to an 11-open reading frame (ORF) plasticity region of the bacterial
      chromosome. By constructing a mutation in fucP (encoding a putative fucose
      permease), one of the genes in the plasticity region, we found that this locus is
      required for fucose utilization. Consistent with their function in fucose
      utilization, transcription of the genes in the locus is highly inducible by
      fucose. PCR screening revealed a broad distribution of this genetic locus in
      strains derived from various host species, and the presence of this locus was
      consistently associated with fucose utilization. Birds inoculated with the fucP
      mutant strain alone were colonized at a level comparable to that by the wild-type
      strain; however, in cocolonization experiments, the mutant was significantly
      outcompeted by the wild-type strain when birds were inoculated with a low dose
      (105 CFU per bird). This advantage was not observed when birds were inoculated at
      a higher inoculum dose (108 CFU per bird). These results demonstrated a
      previously undescribed substrate that supports growth of C. jejuni and identified
      the genetic locus associated with the utilization of this substrate. These
      findings substantially enhance our understanding of the metabolic repertoire of
      C. jejuni and the role of metabolic diversity in Campylobacter pathobiology.

PMID- 21193611
TI  - Control of lipopolysaccharide biosynthesis by FtsH-mediated proteolysis of LpxC
      is conserved in enterobacteria but not in all gram-negative bacteria.
AB  - Despite the essential function of lipopolysaccharides (LPS) in Gram-negative
      bacteria, it is largely unknown how the exact amount of this molecule in the
      outer membrane is controlled. The first committed step in LPS biosynthesis is
      catalyzed by the LpxC enzyme. In Escherichia coli, the cellular concentration of
      LpxC is adjusted by the only essential protease in this organism, the membrane
      anchored metalloprotease FtsH. Turnover of E. coli LpxC requires a length- and
      sequence-specific C-terminal degradation signal. LpxC proteins from Salmonella,
      Yersinia, and Vibrio species carry similar C-terminal ends and, like the E. coli
      enzyme, were degraded by FtsH. Although LpxC proteins are highly conserved in
      Gram-negative bacteria, there are striking differences in their C termini. The
      Aquifex aeolicus enzyme, which is devoid of the C-terminal extension, was stable
      in E. coli, whereas LpxC from the alphaproteobacteria Agrobacterium tumefaciens
      and Rhodobacter capsulatus was degraded by the Lon protease. Proteolysis of the
      A. tumefaciens protein required the C-terminal end of LpxC. High stability of
      Pseudomonas aeruginosa LpxC in E. coli and P. aeruginosa suggested that
      Pseudomonas uses a proteolysis-independent strategy to control its LPS content.
      The differences in LpxC turnover along with previously reported differences in
      susceptibility against antimicrobial compounds have important implications for
      the potential of LpxC as a drug target.

PMID- 21193612
TI  - Characterization and manipulation of the pathway-specific late regulator AlpW
      reveals Streptomyces ambofaciens as a new producer of Kinamycins.
AB  - The genome sequence of Streptomyces ambofaciens, a species known to produce the
      congocidine and spiramycin antibiotics, has revealed the presence of numerous
      gene clusters predicted to be involved in the biosynthesis of secondary
      metabolites. Among them, the type II polyketide synthase-encoding alp cluster was
      shown to be responsible for the biosynthesis of a compound with antibacterial
      activity. Here, by means of a deregulation approach, we gained access to workable
      amounts of the antibiotics for structure elucidation. These compounds, previously
      designated as alpomycin, were shown to be known members of kinamycin family of
      antibiotics. Indeed, a mutant lacking AlpW, a member of the TetR regulator
      family, was shown to constitutively produce kinamycins. Comparative
      transcriptional analyses showed that expression of alpV, the essential regulator
      gene required for activation of the biosynthetic genes, is strongly maintained
      during the stationary growth phase in the alpW mutant, a stage at which alpV
      transcripts and thereby transcripts of the biosynthetic genes normally drop off.
      Recombinant AlpW displayed DNA binding activity toward specific motifs in the
      promoter region of its own gene and that of alpV and alpZ. These recognition
      sequences are also targets for AlpZ, the gamma-butyrolactone-like receptor
      involved in the regulation of the alp cluster. However, unlike that of AlpZ, the
      AlpW DNA-binding ability seemed to be insensitive to the signaling molecules
      controlling antibiotic biosynthesis. Together, the results presented in this
      study reveal S. ambofaciens to be a new producer of kinamycins and AlpW to be a
      key late repressor of the cellular control of kinamycin biosynthesis.

PMID- 21193613
TI  - Exploring the active site of the tungsten, iron-sulfur enzyme acetylene
      hydratase.
AB  - The soluble tungsten, iron-sulfur enzyme acetylene hydratase (AH) from mesophilic
      Pelobacter acetylenicus is a member of the dimethyl sulfoxide (DMSO) reductase
      family. It stands out from its class as it catalyzes a nonredox reaction, the
      addition of H2O to acetylene (H-C=C-H) to form acetaldehyde (CH3CHO). Caught in
      its active W(IV) state, the high-resolution three-dimensional structure of AH
      offers an excellent starting point to tackle its unique chemistry and to identify
      catalytic amino acid residues within the active site cavity: Asp13 close to W(IV)
      coordinated to two molybdopterin-guanosine-dinucleotide ligands, Lys48 which
      couples the [4Fe-4S] cluster to the W site, and Ile142 as part of a hydrophobic
      ring at the end of the substrate access channel designed to accommodate the
      substrate acetylene. A protocol was developed to express AH in Escherichia coli
      and to produce active-site variants which were characterized with regard to
      activity and occupancy of the tungsten and iron-sulfur centers. By this means,
      fusion of the N-terminal chaperone binding site of the E. coli nitrate reductase
      NarG to the AH gene improved the yield and activity of AH and its variants
      significantly. Results from site-directed mutagenesis of three key residues,
      Asp13, Lys48, and Ile142, document their important role in catalysis of this
      unusual tungsten enzyme.

PMID- 21193614
TI  - The American Diabetes Association's 57th annual advanced postgraduate course:
      diabetes risk, vitamin D, polycystic ovary syndrome, and obstructive sleep apnea.

PMID- 21193615
TI  - Maternal glucose at 28 weeks of gestation is not associated with obesity in 2
      year-old offspring: the Belfast Hyperglycemia and Adverse Pregnancy Outcome
      (HAPO) family study: comment on Pettit et al.

PMID- 21193616
TI  - Measuring abdominal obesity: effects of height on distribution of cardiometabolic
      risk factors risk using waist circumference and waist-to-height ratio.

PMID- 21193617
TI  - Pancreatic beta-cell function in women with gestational diabetes mellitus defined
      by new consensus criteria.

PMID- 21193618
TI  - Paternally inherited proinsulin mutations may result in earlier onset of
      monogenic diabetes mutation identity effect in monogenic diabetes.

PMID- 21193619
TI  - Results of a successful telephonic intervention to improve diabetes control in
      urban adults: a randomized trial.
AB  - OBJECTIVE: To compare the effectiveness of a telephonic and a print intervention
      over 1 year to improve diabetes control in low-income urban adults. RESEARCH
      DESIGN AND METHODS: A randomized trial in Spanish and English comparing a
      telephonic intervention implemented by health educators with a print
      intervention. Participants (N = 526) had an A1C >=7.5% and were prescribed one or
      more oral agents. All were members of a union/employer jointly sponsored health
      benefit plan. Health coverage included medications. Primary outcomes were A1C and
      pharmacy claims data; secondary outcomes included self-report of two medication
      adherence measures and other self-care behaviors. RESULTS: Participants were 62%
      black and 23% Hispanic; 77% were foreign born, and 42% had annual family incomes
      <$30 thousand. Baseline median A1C was 8.6% (interquartile range 8.0-10.0).
      Insulin was also prescribed for 24% of participants. The telephone group had mean
      +/- SE decline in A1C of 0.23 +/- 0.11% over 1 year compared with a rise of 0.13
      +/- 0.13% for the print group (P = 0.04). After adjusting for baseline A1C, sex,
      age, and insulin use, the difference in A1C was 0.40% (95% CI 0.10-0.70, P =
      0.009). Change in medication adherence measured by claims data, but not by self
      report measures, was significantly associated with change in A1C (P = 0.01).
      Improvement in medication adherence was associated (P = 0.005) with the
      telephonic intervention, but only among those not taking insulin. No diabetes
      self-care activities were significantly correlated with the change in A1C.
      CONCLUSIONS: A 1-year tailored telephonic intervention implemented by health
      educators was successful in significantly, albeit modestly, improving diabetes
      control compared with a print intervention in a low-income, insured, minority
      population.

PMID- 21193620
TI  - Comparison of near-patient capillary glucose measurement and a risk assessment
      questionnaire in screening for type 2 diabetes in a high-risk population in rural
      India.
AB  - OBJECTIVE: To assess the utility of a point-of-care (POC) capillary blood glucose
      measurement as compared with routine clinical parameters in predicting
      undiagnosed diabetes in a low-resource rural India setting. RESEARCH DESIGN AND
      METHODS: Nine hundred and ninety-four participants aged >30 years and stratified
      by age and sex were randomly selected from 20 villages in India. A clinical
      questionnaire, sampling for laboratory venous fasting plasma glucose (FPG), and
      POC capillary blood glucose assay were performed simultaneously. Diabetes
      diagnosis was based on the World Health Organization (WHO) definition using FPG.
      The capacity of the POC glucose to predict the presence of diabetes was assessed
      and compared with the questionnaire using area under the receiver operating
      characteristic curves (AUCs). RESULTS: The AUC for POC glucose alone in
      predicting diabetes was 0.869 (95% CI 0.810-0.929). This was significantly better
      (P < 0.001 for AUC comparison) than the models based upon clinical variables
      alone (AUC for the best clinical model including age, BMI, hypertension, waist
      circumference: 0.694 [95% CI 0.621-0.766]). POC glucose appropriately
      reclassified the risk of up to one-third of participants ranked according to the
      clinical models. Adding the clinical variables to the POC glucose assay did not
      significantly improve the discriminatory capability beyond that achieved with the
      POC glucose measurement alone (all P > 0.37). CONCLUSIONS: POC glucose testing
      appears to be a simple and reliable tool for identifying undiagnosed diabetes in
      a high-risk, resource-poor rural population. However, studies evaluating the cost
      effectiveness of introducing POC glucose testing are needed prior to widespread
      implementation.

PMID- 21193621
TI  - Depression in diabetes: have we been missing something important?

PMID- 21193622
TI  - New technologies to advance self-management support in diabetes: not just a bunch
      of cool apps!

PMID- 21193623
TI  - Early identification of type 2 diabetes: policy should be aligned with health
      systems strengthening.

PMID- 21193624
TI  - Update of ADA's major position statement, "Standards of Medical Care in
      Diabetes". Introduction.

PMID- 21193626
TI  - Summary of revisions to the 2011 clinical practice recommendations.

PMID- 21193627
TI  - Executive summary: standards of medical care in diabetes--2011.

PMID- 21193628
TI  - Diagnosis and classification of diabetes mellitus.

PMID- 21193629
TI  - Diabetes care in the school and day care setting.

PMID- 21193630
TI  - Diabetes management in correctional institutions.

PMID- 21193631
TI  - Diabetes and employment.

PMID- 21193625
TI  - Standards of medical care in diabetes--2011.

PMID- 21193632
TI  - Third-party reimbursement for diabetes care, self-management education, and
      supplies.

PMID- 21193633
TI  - National Standards for diabetes self-management education.

PMID- 21193638
TI  - Possible roles for Munc18-1 domain 3a and Syntaxin1 N-peptide and C-terminal
      anchor in SNARE complex formation.
AB  - Munc18-1 and Syntaxin1 are essential proteins for SNARE-mediated
      neurotransmission. Munc18-1 participates in synaptic vesicle fusion via dual
      roles: as a docking/chaperone protein by binding closed Syntaxin1, and as a
      fusion protein that binds SNARE complexes in a Syntaxin1 N-peptide dependent
      manner. The two roles are associated with a closed-open Syntaxin1 conformational
      transition. Here, we show that Syntaxin N-peptide binding to Munc18-1 is not
      highly selective, suggesting that other parts of the SNARE complex are involved
      in binding to Munc18-1. We also find that Syntaxin1, with an N peptide and a
      physically anchored C terminus, binds to Munc18-1 and that this complex can
      participate in SNARE complex formation. We report a Munc18-1-N-peptide crystal
      structure that, together with other data, reveals how Munc18-1 might transit from
      a conformation that binds closed Syntaxin1 to one that may be compatible with
      binding open Syntaxin1 and SNARE complexes. Our results suggest the possibility
      that structural transitions occur in both Munc18-1 and Syntaxin1 during their
      binary interaction. We hypothesize that Munc18-1 domain 3a undergoes a
      conformational change that may allow coiled-coil interactions with SNARE
      complexes.

PMID- 21193639
TI  - Self-assembling elastin-like peptides growth factor chimeric nanoparticles for
      the treatment of chronic wounds.
AB  - Chronic wounds are associated with poor epidermal and dermal remodeling. Previous
      work has shown the efficacy of keratinocyte growth factor (KGF) in
      reepithelialization and elastin in dermal wound healing. Here we demonstrate the
      fabrication of a fusion protein comprising of elastin-like peptides and KGF. This
      fusion protein retains the performance characteristics of KGF and elastin as
      evidenced by its enhancement of keratinocyte and fibroblast proliferation. It
      also preserved the characteristic elastin-like peptides inverse phase
      transitioning allowing the recombinant protein to be expressed in bacterial hosts
      (such as Escherichia coli) and purified rapidly and easily using inverse
      temperature cycling. The fusion protein self-assembled into nanoparticles at
      physiological temperatures. When applied to full thickness, wounds in Lepr(db)
      diabetic mice these particles enhanced reepithelialization and granulation, by 2-
      and 3-fold respectively, when compared to the controls. The data strongly
      suggests that these self-assembled nanoparticles may be beneficial in the
      treatment of chronic wounds resulting from diabetes or other underlying
      circulatory conditions.

PMID- 21193641
TI  - Documentation and analysis of aetiology of end-stage renal failure.

PMID- 21193640
TI  - Structural basis for piRNA 2'-O-methylated 3'-end recognition by Piwi PAZ
      (Piwi/Argonaute/Zwille) domains.
AB  - Argonaute and Piwi proteins are key players in the RNA silencing pathway, with
      the former interacting with micro-RNAs (miRNAs) and siRNAs, whereas the latter
      targets piwi-interacting RNAs (piRNAs) that are 2'-O-methylated (2(')-OCH(3)) at
      their 3' ends. Germline-specific piRNAs and Piwi proteins play a critical role in
      genome defense against transposable elements, thereby protecting the genome
      against transposon-induced defects in gametogenesis and fertility. Humans contain
      four Piwi family proteins designated Hiwi1, Hiwi2, Hiwi3, and Hili. We report on
      the structures of Hili-PAZ (Piwi/Argonaute/Zwille) domain in the free state and
      Hiwi1 PAZ domain bound to self-complementary 14-mer RNAs (12-bp + 2-nt overhang)
      containing 2(')-OCH(3) and 2'-OH at their 3' ends. These structures explain the
      molecular basis underlying accommodation of the 2(')-OCH(3) group within a
      preformed Hiwi1 PAZ domain binding pocket, whose hydrophobic characteristics
      account for the preferential binding of 2(')-OCH(3) over 2'-OH 3' ends. These
      results contrast with the more restricted binding pocket for the human Ago1 PAZ
      domain, which exhibits a reverse order, with preferential binding of 2'-OH over
      2(')-OCH(3) 3' ends.

PMID- 21193642
TI  - Interstitial lung diseases after leflunomide use in nephropathy: an analysis of
      reported cases in Chinese literature.
AB  - BACKGROUND: Leflunomide (LEF)-induced interstitial lung disease (ILD) has been
      reported in patients with rheumatoid arthritis. In China, LEF is used off-label
      for the treatment of nephropathy. METHODS: Systemic review of the Chinese
      literature from 1999 to June 2010 for case reports and case series of LEF-induced
      ILD in nephropathy patients. RESULTS: We identified seven cases of LEF-induced
      ILD (three males and four females), with an average age of 45.9 years (range: 9
      69 years). Six cases had primary nephrotic syndrome and one had Henoch-Schoenlein
      purpura. Four cases had diagnoses of renal pathology. Five patients were given
      loading doses of LEF, followed by a maintenance dose of 10-30 mg/day. The mean
      duration of LEF use was 62.9 +/- 33.0 days (range: 20-120 days). The mean
      accumulated dose of LEF was 1192.5 mg (range: 830-1800 mg). LEF therapy was
      considered effective in four patients. Four patients died (57.1%), three of whom
      had developed fevers. All three male patients died and both of the young patients
      died. The mean duration of LEF treatment was 83 days for patients who died and 37
      days for survivors. CONCLUSIONS: LEF-induced ILD in patients with nephropathy
      usually occurred after ~2 months of treatment and an accumulated dose of 1192.5
      mg. Duration of LEF use, male sex, young age and fever seemed to increase the
      risk of mortality.

PMID- 21193643
TI  - Side effects of oseltamivir in end-stage renal failure patients.
AB  - BACKGROUND: Patients with end-stage renal disease who developed H1N1 infections
      have an increased risk of morbidity and mortality. In light of the high incidence
      of H1N1 infections in renal replacement therapy patients in Brunei Darussalam, an
      Oseltamivir (Tamiflu) prophylactic dosing regimen of 75 mg every 5 days for renal
      replacement therapy patients was initiated by the Ministry of Health in August
      2009. The regime was used to serve as a bridge towards an anticipated nationwide
      vaccination programme that was due in September 2009. This study aimed to
      evaluate the side effects, factors that might influence the side effects profile
      and compliance of the dialysis patients that had undergone the month-long
      chemoprophylactic regime. METHODS: A cross-sectional study was carried out on the
      dialysis patients that had undergone the oseltamivir prophylactic regime, which
      involved distribution of questionnaires to participants after the regime was
      completed. RESULTS: Three hundred and thirty-three patients participated in this
      study. 25.7% of sample participants reported at least one side effect
      (experienced during the regime). 97% of participants were found to have reported
      three side effect types or less. The most frequent side effects reported were
      nausea (9.4%), abdominal pain (9.1%) and dizziness (9.1%). Age, gender, dialysis
      types, serum haemoglobin, serum albumin and dialysis clearance measurements were
      found to have no significant associations with the frequency of participants that
      had reported side effects. 11.2% of sample participants made up the non-compliant
      group. The top two reasons for not completing the medication were participants'
      perceived side effects (24.3%) and forgetting to take their medications (56.8%).
      CONCLUSIONS: Side effects were found to be mild and tolerable by participants,
      with no life-threatening events. The study showed that high compliance of this
      regime can be achieved. These results, together with no incidence of H1N1 cases
      in the sample participants, showed that the dosing regimen of 75 mg every 5 days
      in both haemodialysis and continuous ambulatory peritoneal dialysis patients is
      both tolerable and effective and should be considered for future prophylactic
      regimes.

PMID- 21193644
TI  - Intake of water with high levels of dissolved hydrogen (H2) suppresses ischemia
      induced cardio-renal injury in Dahl salt-sensitive rats.
AB  - BACKGROUND: Hydrogen (H(2)) reportedly produces an antioxidative effect by
      quenching cytotoxic oxygen radicals. We studied the biological effects of water
      with dissolved H(2) on ischemia-induced cardio-renal injury in a rat model of
      chronic kidney disease (CKD). METHODS: Dahl salt-sensitive rats (7 weeks old)
      were allowed ad libitum drinking of filtered water (FW: dissolved H(2), 0.00 +/-
      0.00 mg/L) or water with dissolved H(2) produced by electrolysis (EW: dissolved
      H(2), 0.35 +/- 0.03 mg/L) for up to 6 weeks on a 0.5% salt diet. The rats then
      underwent ischemic reperfusion (I/R) of one kidney and were killed a week later
      for investigation of the contralateral kidney and the heart. RESULTS: In the rats
      given FW, unilateral kidney I/R induced significant increases in plasma monocyte
      chemoattractant protein-1, methylglyoxal and blood urea nitrogen. Histologically,
      significant increases were found in glomerular adhesion, cardiac fibrosis, number
      of ED-1 (CD68)-positive cells and nitrotyrosine staining in the contralateral
      kidney and the heart. In rats given EW, those findings were significantly
      ameliorated and there were significant histological differences between rats
      given FW and those given EW. CONCLUSION: Consumption of EW by ad libitum drinking
      has the potential to ameliorate ischemia-induced cardio-renal injury in CKD model
      rats. This indicates a novel strategy of applying H(2) produced by water
      electrolysis technology for the prevention of CKD cardio-renal syndrome.

PMID- 21193645
TI  - 47-year-old woman with dizziness, weakness, and confusion.

PMID- 21193646
TI  - Coma bullae: associations beyond medications.

PMID- 21193648
TI  - Should oncologists routinely discuss fertility preservation with cancer patients
      of childbearing age?

PMID- 21193649
TI  - Refurbishing Mayo Clinic Proceedings: 2011-2012.

PMID- 21193650
TI  - Recent improvements in survival in primary systemic amyloidosis and the
      importance of an early mortality risk score.
AB  - OBJECTIVE: To examine whether the outcome of patients with primary systemic
      amyloidosis (AL) has improved over time and to identify predictors of early
      mortality in patients with AL. PATIENTS AND METHODS: We studied 2 separate
      cohorts of patients. The first cohort, consisting of 1998 patients with AL seen
      at Mayo Clinic between January 1977 and August 2006, was used to examine the
      trends in overall survival (OS) from diagnosis during this 30-year period. The
      second cohort, consisting of 313 patients seen between September 2006 and August
      2009, was used to validate a model for predicting early mortality. RESULTS: The 4
      year OS from diagnosis improved during each decade of follow-up: 21%, 24%, and
      33%, respectively, for the periods 1977-1986, 1987-1996, and 1997-2006 (P<.001).
      Within the last group (1997-2006), 4-year OS during 1997-1999, 2000-2002, and
      2003-2006 was 28%, 30%, and 42%, respectively (P=.02). However, the 1-year
      mortality remained high during the 30-year period. A risk stratification score
      using cardiac troponin T, N-terminal probrain natriuretic peptide, and uric acid
      identified patients at risk of early mortality. The 1-year mortality with 0, 1,
      2, or 3 risk factors was 19%, 37%, 61%, and 80%, respectively, in this training
      cohort of 459 patients. This was confirmed in a validation cohort of 313
      patients. CONCLUSION: Survival in AL has improved over time, with maximum
      improvement occurring in the past decade. However, early mortality remains high,
      and prospective identification of patients at risk of early mortality may allow
      development of risk-adapted strategies.

PMID- 21193651
TI  - Effect of a multidisciplinary fall risk assessment on falls among neurology
      inpatients.
AB  - OBJECTIVE: To evaluate whether the addition of a physician assessment of patient
      fall risk at admission would reduce inpatient falls on a tertiary hospital
      neurology inpatient unit. PATIENTS AND METHODS: A physician fall risk assessment
      was added to the existing risk assessment process (clinical nurse evaluation and
      Hendrich II Fall Risk Model score with specific fall prevention measures for
      patients at risk). An order to select either "Patient is" or "Patient is not at
      high risk of falls by physician assessment" was added to the physician electronic
      admission order set. Nurses and physicians were instructed to reach consensus
      when assessments differed. Full implementation occurred in second-quarter 2008.
      Preimplementation (January 1, 2006, to March 31, 2008) and postimplementation
      (April 1, 2008, to December 31, 2009) rates of falls were compared on the
      neurology inpatient unit and on 6 other medical units that did not receive
      intervention. RESULTS: The rate of falls during the 7 quarters after full
      implementation was significantly lower than that during the 9 preceding quarters
      (4.12 vs 5.69 falls per 1000 patient-days; P=.04), whereas the rate of falls on
      other medical units did not significantly change (2.99 vs 3.33 falls per 1000
      patient-days; P=.24, Poisson test). The consensus risk assessment at admission
      correctly identified patients at risk for falls (14/325 at-risk patients fell vs
      0/147 low-risk patients; P=.01, chi2 test), but the Hendrich II Fall Risk Model
      score, nurse, and physician assessments individually did not. CONCLUSION: A
      multidisciplinary approach to fall risk assessment is feasible, correctly
      identifies patients at risk, and was associated with a reduction in inpatient
      falls.

PMID- 21193652
TI  - The association of active cancer with venous thromboembolism location: a
      population-based study.
AB  - OBJECTIVE: To test active cancer for an association with venous thromboembolism
      (VTE) location. PATIENTS AND METHODS: Using the resources of the Rochester
      Epidemiology Project, we identified all Olmsted County, MN, residents with
      incident VTE during the 35-year period 1966-2000 (N = 3385). We restricted
      analyses to residents with objectively diagnosed VTE during the 17-year period
      from January 1, 1984, to December 31, 2000 (N = 1599). For each patient, we
      reviewed the complete medical records in the community for patient age, gender,
      and most recent body mass index at VTE onset; VTE event type and location; and
      previously identified independent VTE risk factors (ie, surgery, hospitalization
      for acute medical illness, active cancer, leg paresis, superficial venous
      thrombosis, and varicose veins). Using logistic regression we tested active
      cancer for an association with each of 4 symptomatic VTE locations (arm or intra
      abdominal deep venous thrombosis [DVT], intra-abdominal DVT, pulmonary embolism,
      and bilateral leg DVT), adjusted for age, gender, body mass index, and other VTE
      risk factors. RESULTS: In multivariate analyses, active cancer was independently
      associated with arm or intra-abdominal DVT (odds ratio [OR], 1.76; P = .01),
      intra-abdominal DVT (OR, 2.22; P = .004), and bilateral leg DVT (OR, 2.09; P =
      .02), but not pulmonary embolism (OR, 0.93). CONCLUSION: Active cancer is
      associated with VTE location. Location of VTE may be useful in decision making
      regarding cancer screening.

PMID- 21193653
TI  - Enhancing nurse and physician collaboration in clinical decision making through
      high-fidelity interdisciplinary simulation training.
AB  - OBJECTIVE: To determine whether interdisciplinary simulation team training can
      positively affect registered nurse and/or physician perceptions of collaboration
      in clinical decision making. PARTICIPANTS AND METHODS: Between March 1 and April
      21, 2009, a convenience sample of volunteer nurses and physicians was recruited
      to undergo simulation training consisting of a team response to 3 clinical
      scenarios. Participants completed the Collaboration and Satisfaction About Care
      Decisions (CSACD) survey before training and at 2 weeks and 2 months after
      training. Differences in CSACD summary scores between the time points were
      assessed with paired t tests. RESULTS: Twenty-eight health care professionals (19
      nurses, 9 physicians) underwent simulation training. Nurses were of similar age
      to physicians (27.3 vs 34.5 years; p = .82), were more likely to be women (95.0%
      vs 12.5%; p < .001), and were less likely to have undergone prior simulation
      training (0% vs 37.5%; p = .02). The pretest showed that physicians were more
      likely to perceive that open communication exists between nurses and physicians
      (p = .04) and that both medical and nursing concerns influence the decision
      making process (p = .02). Pretest CSACD analysis revealed that most participants
      were dissatisfied with the decision-making process. The CSACD summary score
      showed significant improvement from baseline to 2 weeks (4.2 to 5.1; p < .002), a
      trend that persisted at 2 months (p < .002). CONCLUSION: Team training using high
      fidelity simulation scenarios promoted collaboration between nurses and
      physicians and enhanced the patient care decision-making process.

PMID- 21193654
TI  - Influence of serum sodium on MELD-based survival prediction in alcoholic
      hepatitis.
AB  - OBJECTIVE: To compare the Model for End-Stage Liver Disease (MELD) with the
      modified model including sodium (MELDNa) for predicting 180-day mortality in
      patients with alcoholic hepatitis (AH) and determine the subset in whom serum
      sodium may enhance 180-day mortality prediction. PATIENTS AND METHODS: We
      examined 26 patients with AH enrolled in a prospective trial between June 1,
      2004, and June 30, 2007, at Mayo Clinic. Logistic regression analysis was done to
      assess the effect of MELD and MELDNa scores on 180-day mortality. The C statistic
      was derived to compare MELD with MELDNa in patients with and without ascites.
      RESULTS: MELD (odds ratio [OR], 1.22; 95% confidence interval [CI], 1.05-1.47; P
      = .007; C statistic, 0.81) and MELDNa (OR, 1.24; 95% CI, 1.05-1.56; P = .008; C
      statistic, 0.78) were significant predictors of 180-day mortality in patients
      with AH. A MELD score of 27.0 and a MELDNa score of 28.0 had sensitivity of 76.5%
      and 87.5% and specificity of 64.9% and 52.5%, respectively. In patients with AH
      and ascites, MELDNa (OR, 2.27; 95% CI, 1.22-36.68; P = .008; C statistic, 0.97)
      was a better predictor of 180-day mortality than MELD (OR, 1.37; 95% CI, 1.07
      2.12; P = .006; C statistic, 0.90). A MELD score of 29.0 and a MELDNa score of
      34.0 had sensitivity of 85.7% and 83.3% and specificity of 31.0% and 16.7%,
      respectively. CONCLUSION: MELD and MELDNa were similar predictors of 180-day
      mortality; however, MELDNa was a better predictor of mortality than MELD in
      patients with ascites. Hyponatremia in patients with AH without ascites is not a
      predictor of mortality because it may have a dilutional basis secondary to
      excessive intake of low-osmolar alcohol.

PMID- 21193655
TI  - Fertility preservation.
AB  - Of the estimated 1.5 million men and women who were diagnosed as having cancer in
      2010, approximately 10% are younger than 45 years. For these individuals, cancer
      treatment can be lifesaving but can permanently affect reproductive capacity. The
      American Society of Clinical Oncology has recommended that oncologists discuss
      the possibility of infertility with reproductive-age cancer patients and offer
      referral for fertility preservation consultation and therapy. Fertility
      preservation is an emerging field that offers treatment aimed at protecting
      future reproductive ability for individuals with cancer or other serious
      illnesses. Although fertility preservation strategies vary by patient age and
      sex, many allow patients to store gametes or reproductive tissues for potential
      future use to create offspring. As an emerging discipline, many questions remain
      about the role of fertility preservation. We performed a MEDLINE search from 1950
      to June 2010 using the following MeSH terms: amenorrhea; antineoplastic agents;
      ovarian failure; premature; infertility, female; fertility preservation;
      infertility, male; adolescent and cancer; child and cancer; cryopreservation; and
      reproductive technologies, assisted. Studies considered for inclusion included
      those written in English and published before June 2010.

PMID- 21193656
TI  - Vitamin D insufficiency.
AB  - Vitamin D deficiency, which classically manifests as bone disease (either rickets
      or osteomalacia), is characterized by impaired bone mineralization. More
      recently, the term vitamin D insufficiency has been used to describe low levels
      of serum 25-hydroxyvitamin D that may be associated with other disease outcomes.
      Reliance on a single cutoff value to define vitamin D deficiency or insufficiency
      is problematic because of the wide individual variability of the functional
      effects of vitamin D and interaction with calcium intakes. In adults, vitamin D
      supplementation reduces the risk of fractures and falls. The evidence for other
      purported beneficial effects of vitamin D is primarily based on observational
      studies. We selected studies with the strongest level of evidence for clinical
      decision making related to vitamin D and health outcomes from our personal
      libraries of the vitamin D literature and from a search of the PubMed database
      using the term vitamin D in combination with the following terms related to the
      potential nonskeletal benefits of vitamin D: mortality, cardiovascular, diabetes
      mellitus, cancer, multiple sclerosis, allergy, asthma, infection, depression,
      psychiatric, and pain. Conclusive demonstration of these benefits awaits the
      outcome of controlled clinical trials.

PMID- 21193657
TI  - Coccidioidomycosis in African Americans.
AB  - Coccidioidomycosis is caused by Coccidioides species, a fungus endemic to the
      desert regions of the southwestern United States, and is of particular concern
      for African Americans. We performed a PubMed search of the English-language
      medical literature on coccidioidomycosis in African Americans and summarized the
      pertinent literature. Search terms were coccidioidomycosis, Coccidioides, race,
      ethnicity, African, black, and Negro. The proceedings of the national and
      international coccidioidomycosis symposia were searched. All relevant articles
      and their cited references were reviewed; those with epidemiological,
      immunologic, clinical, and therapeutic data pertaining to coccidioidomycosis in
      African Americans were included in the review. Numerous studies documented an
      increased predilection for severe coccidioidal infections, coccidioidomycosis
      related hospitalizations, and extrapulmonary dissemination in persons of African
      descent; however, most of the published studies are variably problematic. The
      immunologic mechanism for this predilection is unclear. The clinical features and
      treatment recommendations are summarized. Medical practitioners need to be alert
      to the possibility of coccidioidomycosis in persons with recent travel to or
      residence in an area where the disease is endemic.

PMID- 21193658
TI  - Clinical pearls in general internal medicine.

PMID- 21193659
TI  - 37-year-old woman with palpitations and fatigue.

PMID- 21193660
TI  - Lag phase of Salmonella enterica under osmotic stress conditions.
AB  - Salmonella enterica serovar Typhimurium was grown at salt concentrations ranging
      from 0.5 to 7.5% in minimal medium with and without added osmoprotectant and in a
      rich medium. In minimal medium, the cells showed an initial decline period, and
      consequently the definition of the lag time of the resultant log count curve was
      revised. The model of Baranyi and Roberts (Int. J. Food Microbiol. 23:277-294,
      1994) was modified to take into account the initial decline period, based on the
      assumption that the log count curve of the total population was the sum of a
      dying and a surviving-then-growing subpopulation. The lag time was defined as the
      lag of the surviving subpopulation. It was modeled by means of a parameter
      quantifying the biochemical work the surviving cells carry out during this phase,
      the "work to be done." The logarithms of the maximum specific growth rates as a
      function of the water activity in the three media differed only by additive
      constants, which gave a theoretical basis for bias factors characterizing the
      relationships between different media. Models for the lag and the "work to be
      done" as a function of the water activity showed similar properties, but in rich
      medium above 5% salt concentrations, the data showed a maximum for this work. An
      accurate description of the lag time is important to avoid food wastage, which is
      an issue of increasing significance in the food industry, while maintaining food
      safety standards.

PMID- 21193661
TI  - Metallic copper as an antimicrobial surface.
AB  - Bacteria, yeasts, and viruses are rapidly killed on metallic copper surfaces, and
      the term "contact killing" has been coined for this process. While the phenomenon
      was already known in ancient times, it is currently receiving renewed attention.
      This is due to the potential use of copper as an antibacterial material in health
      care settings. Contact killing was observed to take place at a rate of at least 7
      to 8 logs per hour, and no live microorganisms were generally recovered from
      copper surfaces after prolonged incubation. The antimicrobial activity of copper
      and copper alloys is now well established, and copper has recently been
      registered at the U.S. Environmental Protection Agency as the first solid
      antimicrobial material. In several clinical studies, copper has been evaluated
      for use on touch surfaces, such as door handles, bathroom fixtures, or bed rails,
      in attempts to curb nosocomial infections. In connection to these new
      applications of copper, it is important to understand the mechanism of contact
      killing since it may bear on central issues, such as the possibility of the
      emergence and spread of resistant organisms, cleaning procedures, and questions
      of material and object engineering. Recent work has shed light on mechanistic
      aspects of contact killing. These findings will be reviewed here and juxtaposed
      with the toxicity mechanisms of ionic copper. The merit of copper as a hygienic
      material in hospitals and related settings will also be discussed.

PMID- 21193663
TI  - Role of the cell wall microenvironment in expression of a heterologous SpaP-S1
      fusion protein by Streptococcus gordonii.
AB  - The charge density in the cell wall microenvironment of Gram-positive bacteria is
      believed to influence the expression of heterologous proteins. To test this, the
      expression of a SpaP-S1 fusion protein, consisting of the surface protein SpaP of
      Streptococcus mutans and a pertussis toxin S1 fragment, was studied in the live
      vaccine candidate bacterium Streptococcus gordonii. Results showed that the
      parent strain PM14 expressed very low levels of SpaP-S1. By comparison, the dlt
      mutant strain, which has a mutation in the dlt operon preventing d-alanylation of
      the cell wall lipoteichoic acids, and another mutant strain, OB219(pPM14), which
      lacks the LPXTG major surface proteins SspA and SspB, expressed more SpaP-S1 than
      the parent. Both the dlt mutant and the OB219(pPM14) strain had a more negatively
      charged cell surface than PM14, suggesting that the negative charged cell wall
      played a role in the increase in SpaP-S1 production. Accordingly, the addition of
      Ca(2+), Mg(2+), and K(+), presumably increasing the positive charge of the cell
      wall, led to a reduction in SpaP-S1 production, while the addition of bicarbonate
      resulted in an increase in SpaP-S1 production. The level of SpaP-S1 production
      could be correlated with the level of PrsA, a peptidyl-prolyl cis/trans
      isomerase, in the cells. PrsA expression appears to be regulated by the cell
      envelope stress two-component regulatory system LiaSR. The results collectively
      indicate that the charge density of the cell wall microenvironment can modulate
      heterologous SpaP-S1 protein expression in S. gordonii and that this modulation
      is mediated by the level of PrsA, whose expression is regulated by the LiaSR two
      component regulatory system.

PMID- 21193662
TI  - Inactivation of a human norovirus surrogate by high-pressure processing:
      effectiveness, mechanism, and potential application in the fresh produce
      industry.
AB  - Fresh produce is often a high-risk food for norovirus contamination because it
      can become contaminated at both preharvest and postharvest stages and it
      undergoes minimal or no processing. Currently, there is no effective method to
      eliminate the viruses from fresh produce. This study systematically investigated
      the effectiveness of high-pressure processing (HPP) on inactivating murine
      norovirus (MNV-1), a surrogate for human norovirus, in aqueous medium and fresh
      produce. We demonstrated that MNV-1 was effectively inactivated by HPP. More than
      a 5-log-PFU/g reduction was achieved in all tested fresh produce when it was
      pressurized at 400 MPa for 2 min at 4 degrees C. We found that pressure, pH,
      temperature, and food matrix affected the virus survival in foods. MNV-1 was more
      effectively inactivated at 4 degrees C than at 20 degrees C in both medium and
      fresh produce. MNV-1 was also more sensitive to HPP at neutral pH than at acidic
      pH. We further demonstrated that disruption of viral capsid structure, but not
      degradation of viral genomic RNA, is the primary mechanism of virus inactivation
      by HPP. However, HPP does not degrade viral capsid protein, and the pressurized
      capsid protein was still antigenic. Overall, HPP had a variable effect on the
      sensorial quality of fresh produce, depending on the pressure level and type of
      product. Taken together, HPP effectively inactivated a human norovirus surrogate
      in fresh produce with a minimal impact on food quality and thus can provide a
      novel intervention for processing fruits intended for frozen storage and related
      products such as purees, sauces, and juices.

PMID- 21193664
TI  - Saccharomyces cerevisiae genome-wide mutant screen for sensitivity to 2,4
      diacetylphloroglucinol, an antibiotic produced by Pseudomonas fluorescens.
AB  - 2,4-Diacetylphloroglucinol (2,4-DAPG), an antibiotic produced by Pseudomonas
      fluorescens, has broad-spectrum antibiotic activity, inhibiting organisms ranging
      from viruses, bacteria, and fungi to higher plants and mammalian cells. The
      biosynthesis and regulation of 2,4-DAPG in P. fluorescens are well described, but
      the mode of action against target organisms is poorly understood. As a first step
      to elucidate the mechanism, we screened a deletion library of Saccharomyces
      cerevisiae in broth and agar medium supplemented with 2,4-DAPG. We identified 231
      mutants that showed increased sensitivity to 2,4-DAPG under both conditions,
      including 22 multidrug resistance-related mutants. Three major physiological
      functions correlated with an increase in sensitivity to 2,4-DAPG: membrane
      function, reactive oxygen regulation, and cell homeostasis. Physiological studies
      with wild-type yeast validated the results of the mutant screens. The chemical
      genetic fitness profile of 2,4-DAPG resembled those of menthol, sodium azide, and
      hydrogen peroxide determined in previous high-throughput screening studies.
      Collectively, these findings indicate that 2,4-DAPG acts on multiple basic
      cellular processes.

PMID- 21193665
TI  - Analyses of both the alkB gene transcriptional start site and alkB promoter
      inducing properties of Rhodococcus sp. strain BCP1 grown on n-alkanes.
AB  - Rhodococcus sp. strain BCP1, known for its capacity to grow on short-chain n
      alkanes (C(2) to C(7)) and to cometabolize chlorinated solvents, was found to
      also utilize medium- and long-chain n-alkanes (C(12) to C(24)) as energy and
      carbon sources. To examine this feature in detail, a chromosomal region which
      includes the alkB gene cluster encoding a non-heme di-iron monooxygenase (alkB),
      two rubredoxins, and one rubredoxin reductase was cloned from the BCP1 genome.
      Furthermore, the activity of the alkB gene promoter (P(alkB)) was examined in the
      presence of gaseous, liquid, and solid n-alkanes along with intermediates of the
      putative n-alkane degradation pathway. A recombinant plasmid, pTP(alkB)LacZ, was
      constructed by inserting the lacZ gene downstream of P(alkB), and it was used to
      transform Rhodococcus sp. strain BCP1. Measurements of beta-galactosidase
      activity showed that P(alkB) is induced by C(6) to C(22) n-alkanes. Conversely,
      C(2) to C(5) and >C(22) n-alkanes and alkenes, such as hexene, were not inducers
      of alkB expression. The effects on P(alkB) expression induced by alternative
      carbon sources along with putative products of n-hexane metabolism were also
      evaluated. This report highlights the great versatility of Rhodococcus sp. strain
      BCP1 and defines for the first time the alkB gene transcriptional start site and
      the alkB promoter-inducing capacities for substrates different from n-alkanes in
      a Rhodococcus strain.

PMID- 21193666
TI  - Identification and characterization of novel and potent transcription promoters
      of Francisella tularensis.
AB  - Two alternative promoter trap libraries, based on the green fluorescence protein
      (gfp) reporter and on the chloramphenicol acetyltransferase (cat) cassette, were
      constructed for isolation of potent Francisella tularensis promoters. Of the
      26,000 F. tularensis strain LVS gfp library clones, only 3 exhibited visible
      fluorescence following UV illumination and all appeared to carry the
      bacterioferritin promoter (Pbfr). Out of a total of 2,000 chloramphenicol
      resistant LVS clones isolated from the cat promoter library, we arbitrarily
      selected 40 for further analysis. Over 80% of these clones carry unique F.
      tularensis DNA sequences which appear to drive a wide range of protein
      expression, as determined by specific chloramphenicol acetyltransferase (CAT)
      Western dot blot and enzymatic assays. The DNA sequence information for the 33
      unique and novel F. tularensis promoters reported here, along with the results of
      in silico and primer extension analyses, suggest that F. tularensis possesses
      classical Escherichia coli sigma(70)-related promoter motifs. These motifs
      include the -10 (TATAAT) and -35 [TTGA(C/T)A] domains and an AT-rich region
      upstream from -35, reminiscent of but distinct from the E. coli upstream region
      that is termed the UP element. The most efficient promoter identified (Pbfr)
      appears to be about 10 times more potent than the F. tularensis groEL promoter
      and is probably among the strongest promoters in F. tularensis. The battery of
      promoters identified in this work will be useful, among other things, for genetic
      manipulation in the background of F. tularensis intended to gain better
      understanding of the mechanisms involved in pathogenesis and virulence, as well
      as for vaccine development studies.

PMID- 21193667
TI  - Kinetics of hydrothermal inactivation of endotoxins.
AB  - A kinetic model was established for the inactivation of endotoxins in water at
      temperatures ranging from 210 degrees C to 270 degrees C and a pressure of 6.2 *
      10(6) Pa. Data were generated using a bench scale continuous-flow reactor system
      to process feed water spiked with endotoxin standard (Escherichia coli O113:H10).
      Product water samples were collected and quantified by the Limulus amebocyte
      lysate assay. At 250 degrees C, 5-log endotoxin inactivation was achieved in
      about 1 s of exposure, followed by a lower inactivation rate. This non-log-linear
      pattern is similar to reported trends in microbial survival curves. Predictions
      and parameters of several non-log-linear models are presented. In the fast
      reaction zone (3- to 5-log reduction), the Arrhenius rate constant fits well at
      temperatures ranging from 120 degrees C to 250 degrees C on the basis of data
      from this work and the literature. Both biphasic and modified Weibull models are
      comparable to account for both the high and low rates of inactivation in terms of
      prediction accuracy and the number of parameters used. A unified representation
      of thermal resistance curves for a 3-log reduction and a 3 D value associated
      with endotoxin inactivation and microbial survival, respectively, is presented.

PMID- 21193668
TI  - Quantitative PCR coupled with melt curve analysis for detection of selected
      pseudo-nitzschia spp. (Bacillariophyceae) from the Northwestern Mediterranean
      sea.
AB  - The frequency and intensity of Pseudo-nitzschia spp. blooms along the coast of
      Catalonia have been increasing over the past 20 years. As species from this genus
      that are documented as toxigenic have been found in local waters, with both toxic
      and nontoxic species cooccurring in the same bloom, there is a need to develop
      management tools for discriminating the difference. Currently, differentiation of
      toxic and nontoxic species requires time-consuming electron microscopy to
      distinguish taxonomic features that would allow identification as to species, and
      cryptic species can still remain misidentified. In this study, cells of Pseudo
      nitzschia from clonal cultures isolated from seawater were characterized to their
      species identity using scanning electron microscopy, and subsamples of each
      culture were used to create an internal transcribed spacer 1 (ITS-1), 5.8S, and
      ITS-2 ribosomal DNA database for development of species-specific quantitative PCR
      (qPCR) assays. Once developed, these qPCR assays were applied to field samples
      collected over a 2-year period in Alfaques Bay in the northwestern Mediterranean
      Sea to evaluate the possibility of a comprehensive surveillance for all Pseudo
      nitzschia spp. using molecular methods to supplement optical microscopy, which
      can discern taxonomy only to the genus level within this taxon. Total Pseudo
      nitzschia cell density was determined by optical microscopy from water samples
      collected weekly and compared to results obtained from the sum of eight Pseudo
      nitzschia species-specific qPCR assays using duplicate samples. Species-specific
      qPCR followed by melt curve analysis allowed differentiation of amplicons and
      identification of false positives, and results correlated well with the total
      Pseudo-nitzschia cell counts from optical microscopy.

PMID- 21193669
TI  - Phosphate transporter genes as reliable gene markers for the identification and
      discrimination of arbuscular mycorrhizal fungi in the genus glomus.
AB  - An inorganic phosphate transporter gene sequence (852-bp section) allowed
      discrimination between 10 Glomus fungal species represented by 25 strains. It was
      particularly valuable in differentiating between morphologically similar species
      with nucleotide and amino acid sequence differences higher than 3%. This gene is
      proposed as a reliable barcode for the Glomeromycetes.

PMID- 21193670
TI  - Development of an aerosol surface inoculation method for bacillus spores.
AB  - A method was developed to deposit Bacillus subtilis spores via aerosolization
      onto various surface materials for biological agent decontamination and detection
      studies. This new method uses an apparatus coupled with a metered dose inhaler to
      reproducibly deposit spores onto various surfaces. A metered dose inhaler was
      loaded with Bacillus subtilis spores, a surrogate for Bacillus anthracis. Five
      different material surfaces (aluminum, galvanized steel, wood, carpet, and
      painted wallboard paper) were tested using this spore deposition method. This
      aerosolization method deposited spores at a concentration of more than 10(7) CFU
      per coupon (18-mm diameter) with less than a 50% coefficient of variation,
      showing that the aerosolization method developed in this study can deposit
      reproducible numbers of spores onto various surface coupons. Scanning electron
      microscopy was used to probe the spore deposition patterns on test coupons. The
      deposition patterns observed following aerosol impaction were compared to those
      of liquid inoculation. A physical difference in the spore deposition patterns was
      observed to result from the two different methods. The spore deposition method
      developed in this study will help prepare spore coupons via aerosolization fast
      and reproducibly for bench top decontamination and detection studies.

PMID- 21193671
TI  - Plasmid-mediated quinolone resistance in pseudomonas putida isolates from
      imported shrimp.
AB  - Fourteen quinolone-resistant Pseudomonas putida isolates were recovered from
      imported frozen shrimp sold in the United States. Two isolates harbored plasmids
      with qnrA and qnrB genes. PCR and DNA sequencing of quinolone resistance
      determining regions identified novel substitutions in GyrA (His139->Glu and
      Thr128->Ala) and GyrB (Thr442->Asn, Gly470->Ala, and Ile487->Pro) and previously
      reported substitutions in GyrB (Asp489->Glu) and ParC (Thr105->Pro).

PMID- 21193672
TI  - Specific real-time PCR for simultaneous detection and identification of
      Legionella pneumophila serogroup 1 in water and clinical samples.
AB  - Legionella pneumophila, a bacterium that replicates within aquatic amoebae and
      persists in the environment as a free-living microbe, is the causative agent of
      Legionnaires' disease. Among the many Legionella species described, L.
      pneumophila is associated with 90% of human disease, and within the 15 serogroups
      (Sg), L. pneumophila Sg1 causes more than 84% of Legionnaires' disease worldwide.
      Thus, rapid and specific identification of L. pneumophila Sg1 is of the utmost
      importance for evaluation of the contamination of collective water systems and
      the risk posed. Previously we had shown that about 20 kb of the 33-kb locus
      carrying the genes coding for the proteins involved in lipopolysaccharide
      biosynthesis (LPS gene cluster) by L. pneumophila was highly specific for Sg1
      strains and that three genes (lpp0831, wzm, and wzt) may serve as genetic
      markers. Here we report the sequencing and comparative analyses of this specific
      region of the LPS gene cluster in L. pneumophila Sg6, -10, -12, -13, and -14.
      Indeed, the wzm and wzt genes were present only in the Sg1 LPS gene cluster,
      which showed a very specific gene content with respect to the other five
      serogroups investigated. Based on this observation, we designed primers and
      developed a classical and a real-time PCR method for the detection and
      simultaneous identification of L. pneumophila Sg1 in clinical and environmental
      isolates. Evaluation of the selected primers with 454 Legionella and 38 non
      Legionella strains demonstrated 100% specificity. Sensitivity, specificity, and
      predictive values were further evaluated with 209 DNA extracts from water samples
      of hospital water supply systems and with 96 respiratory specimens. The results
      showed that the newly developed quantitative Sg1-specific PCR method is a highly
      specific and efficient tool for the surveillance and rapid detection of high-risk
      L. pneumophila Sg1 in water and clinical samples.

PMID- 21193673
TI  - Metabolic engineering of Saccharomyces cerevisiae for production of
      Eicosapentaenoic Acid, using a novel {Delta}5-Desaturase from Paramecium
      tetraurelia.
AB  - Very-long-chain polyunsaturated fatty acids, such as arachidonic acid (ARA),
      eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), have well-documented
      importance in human health and nutrition. Sustainable production in robust host
      organisms that do not synthesize them naturally requires the coordinated
      expression of several heterologous desaturases and elongases. In the present
      study we show production of EPA in Saccharomyces cerevisiae using glucose as the
      sole carbon source through expression of five heterologous fatty acid desaturases
      and an elongase. Novel Delta5-desaturases from the ciliate protozoan Paramecium
      tetraurelia and from the microalgae Ostreococcus tauri and Ostreococcus
      lucimarinus were identified via a BLAST search, and their substrate preferences
      and desaturation efficiencies were assayed in a yeast strain producing the omega6
      and omega3 fatty acid substrates for Delta5-desaturation. The Delta5-desaturase
      from P. tetraurelia was up-to-2-fold more efficient than the microalgal
      desaturases and was also more efficient than Delta5-desaturases from Mortierella
      alpina and Leishmania major. In vivo investigation of acyl carrier substrate
      specificities showed that the Delta5-desaturases from P. tetraurelia, O.
      lucimarinus, O. tauri, and M. alpina are promiscuous toward the acyl carrier
      substrate but prefer phospholipid-bound substrates. In contrast, the Delta5
      desaturase from L. major showed no activity on phospholipid-bound substrate and
      thus appears to be an exclusively acyl coenzyme A-dependent desaturase.

PMID- 21193674
TI  - Viability of Bacillus licheniformis and Bacillus thuringiensis spores as a model
      for predicting the fate of bacillus anthracis spores during composting of dead
      livestock.
AB  - Safe disposal of dead livestock and contaminated manure is essential for the
      effective control of infectious disease outbreaks. Composting has been shown to
      be an effective method of disposal, but no information exists on its ability to
      contain diseases caused by spore-forming bacteria, such as Bacillus anthracis.
      Duplicate composters (east and west), each containing 16 dead cattle, were
      constructed (final capacity, 85,000 kg). Spores (10(7) CFU/g manure) of Bacillus
      licheniformis and Bacillus thuringiensis were mixed with autoclaved feedlot
      manure and placed in either sterile vials or porous nylon bags. Compost
      temperatures in the west composter were slightly higher than in the east
      composter. Viable B. thuringiensis spores were reduced to <=10(2) CFU in all
      samples after 112 days but were isolated from bags (west composter) at <=10(2)
      and at 10(5) CFU (east composter) after 230 days. In contrast, B. licheniformis
      was at <=10(2) CFU in vials (west composter) after 112 days but remained at 10(6)
      CFU after 230 days (east composter). Similarly, B. licheniformis in bags was not
      detected after 230 days in the west composter but remained at 10(7) CFU in the
      east composter. Our study suggests that spore viability was reduced in the west
      composter by exposure to compost and elevated temperatures over time. Different
      temperature profiles may explain why spores remained viable in the east structure
      but were largely rendered nonviable in the west structure. Under practical
      conditions, variation in composting microclimates may preclude the complete
      inactivation of Bacillus spores, including those of B. anthracis, during
      composting. However, composting may still have merit as a method of
      biocontainment, reducing and diluting the transfer of infectious spores into the
      environment.

PMID- 21193675
TI  - Comparison of Arcobacter isolation methods, and diversity of Arcobacter spp. in
      Cheshire, United Kingdom.
AB  - The aims of this study were, firstly, to compare five published methods for the
      isolation of Arcobacter spp. from animal feces in order to determine the most
      sensitive and specific method. Second, we analyzed the resulting isolates by
      multilocus sequence typing (MLST) in order to investigate the diversity of the
      isolates recovered. Third, we investigated the ability to recover Arcobacter spp.
      from frozen fecal samples. Seventy-seven fecal samples from cattle, sheep, and
      badgers were subjected to five isolation methods, based on published methods for
      the isolation of Arcobacter and Campylobacter spp. Thirty-nine Arcobacter
      butzleri isolates were analyzed using a multilocus sequence typing scheme. The
      survival of Arcobacter spp. in frozen samples was investigated by freezing the
      fecal samples at -80 degrees C for 7 days and then applying the same five
      isolation methods. The most sensitive and specific method used an Arcobacter
      specific broth in conjunction with modified charcoal cefoperazone deoxycholate
      agar (mCCDA) with added antibiotics. Freezing of fecal samples led to a reduction
      in the recovery of Arcobacter spp. by approximately 50%. The 39 allelic profiles
      obtained by MLST could be divided into 11 sequence types (STs). We have
      identified the most sensitive and specific method for the isolation of Arcobacter
      spp. from animal feces and demonstrated that the freezing of fecal samples prior
      to isolation reduces arcobacter recovery. MLST analysis of the isolates revealed
      a high level of diversity.

PMID- 21193676
TI  - Real-time solvent tolerance analysis of pseudomonas sp. strain VLB120{Delta}C
      catalytic biofilms.
AB  - Biofilms are ubiquitous surface-associated microbial communities embedded in an
      extracellular polymeric (EPS) matrix, which gives the biofilm structural
      integrity and strength. It is often reported that biofilm-grown cells exhibit
      enhanced tolerance toward adverse environmental stress conditions, and thus there
      has been a growing interest in recent years to use biofilms for biotechnological
      applications. We present a time- and locus-resolved, noninvasive, quantitative
      approach to study biofilm development and its response to the toxic solvent
      styrene. Pseudomonas sp. strain VLB120DeltaC-BT-gfp1 was grown in modified flow
      cell reactors and exposed to the solvent styrene. Biofilm-grown cells displayed
      stable catalytic activity, producing (S)-styrene oxide continuously during the
      experimental period. The pillar-like structure and growth rate of the biofilm was
      not influenced by the presence of the solvent. However, the cells experience
      severe membrane damage during styrene treatment, although they obviously are able
      to adapt to the solvent, as the amount of permeabilized cells decreased from 75
      to 80% down to 40% in 48 h. Concomitantly, the fraction of concanavalin A (ConA)
      stainable EPS increased, substantiating the assumption that those polysaccharides
      play a major role in structural integrity and enhanced biofilm tolerance toward
      toxic environments. Compared to control experiments with planktonic grown cells,
      the Pseudomonas biofilm adapted much better to toxic concentrations of styrene,
      as nearly 65% of biofilm cells were not permeabilized (viable), compared to only
      7% in analogous planktonic cultures. These findings underline the robustness of
      biofilms under stress conditions and its potential for fine chemical syntheses.

PMID- 21193677
TI  - Biochemical characteristics of the novel haloalkane dehalogenase DatA, isolated
      from the plant pathogen Agrobacterium tumefaciens C58.
AB  - We report the biochemical characterization of a novel haloalkane dehalogenase,
      DatA, isolated from the plant pathogen Agrobacterium tumefaciens C58. DatA
      possesses a peculiar pair of halide-stabilizing residues, Asn-Tyr, which have not
      been reported to play this role in other known haloalkane dehalogenases. DatA has
      a number of other unique characteristics, including substrate-dependent and
      cooperative kinetics, a dimeric structure, and excellent enantioselectivity
      toward racemic mixtures of chiral brominated alkanes and esters.

PMID- 21193678
TI  - Efficient homofermentative L-(+)-lactic acid production from xylose by a novel
      lactic acid bacterium, Enterococcus mundtii QU 25.
AB  - Enterococcus mundtii QU 25, a newly isolated lactic acid bacterium, efficiently
      metabolized xylose into l-lactate. In batch fermentations, the strain produced
      964 mM l-(+)-lactate from 691 mM xylose, with a yield of 1.41 mol/mol xylose
      consumed and an extremely high optical purity of >=99.9% without acetate
      production.

PMID- 21193679
TI  - Comparison of three different pelvic circumferential compression devices: a
      biomechanical cadaver study.
AB  - BACKGROUND: Pelvic circumferential compression devices are designed to stabilize
      the pelvic ring and reduce the volume of the pelvis following trauma. It is
      uncertain whether pelvic circumferential compression devices can be safely
      applied for all types of pelvic fractures because the effects of the devices on
      the reduction of fracture fragments are unknown. The aim of this study was to
      compare the effects of circumferential compression devices on the dynamic
      realignment and final reduction of the pelvic fractures as a measure of the
      quality of reduction. METHODS: Three circumferential compression devices were
      evaluated: the Pelvic Binder, the SAM Sling, and the T-POD. In sixteen cadavers,
      four fracture types were generated according to the Tile classification system.
      Infrared retroreflective markers were fixed in the different fracture fragments
      of each pelvis. The circumferential compression device was applied sequentially
      in a randomized order with gradually increasing forces applied. Fracture fragment
      movement was studied with use of a three-dimensional infrared video system.
      Dynamic realignment and final reduction of the fracture fragments during closure
      of the circumferential compression devices were determined. A factorial repeated
      measures analysis of variance with pairwise post hoc comparisons was performed to
      analyze the differences in pulling force between the circumferential compression
      devices. RESULTS: In the partially stable and unstable (Tile type-B and C) pelvic
      fractures, all circumferential compression devices accomplished closure of the
      pelvic ring and consequently reduced the pelvic volume. No adverse fracture
      displacement (>5 mm) was observed in these fracture types. The required pulling
      force to attain complete reduction at the symphysis pubis varied substantially
      among the three different circumferential compression devices, with a mean (and
      standard error of the mean) of 43 +/- 7 N for the T-POD, 60 +/- 9 N for the
      Pelvic Binder, and 112 +/- 10 N for the SAM Sling. CONCLUSIONS: The Pelvic
      Binder, SAM Sling, and T-POD provided sufficient reduction in partially stable
      and unstable (Tile type-B1 and C) pelvic fractures. No undesirable overreduction
      was noted. The pulling force that was needed to attain complete reduction of the
      fracture parts varied significantly among the three devices, with the T-POD
      requiring the lowest pulling force for fracture reduction.

PMID- 21193680
TI  - Sulfated polysaccharide fucoidan ameliorates experimental autoimmune myocarditis
      in rats.
AB  - Homing of cardiac myosin-specific CD4-positive T cells into the myocardium is the
      initial pathologic event of experimental autoimmune myocarditis (EAM).
      Subsequently, various bystander inflammatory cells are recruited into the
      myocardium crossing vascular endothelial cell walls. Sulfated polysaccharide
      fucoidan binds selectin nonselectively and blocks its function. Therefore, this
      study was designed to evaluate whether in vivo fucoidan treatment can improve
      EAM. A 21-day infusion of physiological saline or fucoidan was administrated
      intraperitoneally to the rats with sham operation (sham-saline, n = 5; sham
      fucoidan, n = 6) or those with cardiac myosin injection (EAM-saline, n = 10; EAM
      fucoidan, n = 10). After 3 weeks, fucoidan treatment improved left ventricular
      ejection fraction (79.04 +/- 2.81 vs 65.94% +/- 3.22%; P < .01 vs EAM-saline)
      with a reduced ratio of heart weight to body weight (4.016 +/- 0.239 vs 4.975 +/-
      0.252 mg/g; P < .05 vs EAM-saline) in EAM. Furthermore, fucoidan treatment
      decreased serum levels of BNP (292.0 +/- 53.4 vs 507.4 +/- 89.2 ng/mL; P < .05 vs
      EAM-saline) and the myocarditis area (31.66 +/- 1.53 vs 42.51% +/- 3.24%; P < .01
      vs EAM-saline) in EAM. These beneficial effects of fucoidan were accompanied by
      inhibition of both macrophage and CD4-positive T-cell infiltration into the
      myocardium. Fucoidan, a nonselective selectin blocker, attenuates the progression
      of EAM. This observation may be explained, at least in part, by blocking the
      extravasation of inflammatory cells into the myocardium.

PMID- 21193681
TI  - Meta-analysis of Renin-Angiotensin-aldosterone blockade for heart failure in
      presence of preserved left ventricular function.
AB  - BACKGROUND: Heart failure (HF) with a preserved left ventricular (LV) ejection
      fraction (EF) is the leading cause of hospitalization after 65 years of age.
      Individual randomized trials have not shown benefits conferred by angiotensin
      converting enzyme (ACE) inhibitors or angiotensin-II receptor blockers (ARB) in
      these patients. To overcome this limitation, we performed a meta-analysis of the
      randomized trials of ACE inhibitors or ARB in patients with HF and preserved
      LVEF. METHODS: Our search identified 4 randomized trials, comprising a total of
      8152 patients, that investigated the effects of ACE inhibitors (n = 1), ARB (n =
      2), or both treatments (n = 1). Risk ratios (RR) and 95% confidence intervals
      (CI) were calculated using a fixed-effect estimate method in the randomised
      trials. RESULTS: Compared with placebo or no treatment, treatment with ACE
      inhibition or ARB was associated with lower rates of hospitalization for HF (RR
      0.90; 95% CI 0.81-0.99, P = .032), though not cardiovascular mortality (RR 1.01;
      95% CI 0.90-1.13, P = 0.858). In 3 studies where these endpoints were combined,
      the 1-year incidence of cardiovascular death or hospitalization for HF was
      lowered by ACE inhibition or ARB (RR 0.74; 95% CI 0.58-0.94, P = .014).
      CONCLUSION: Compared with placebo, ACE inhibition or ARB significantly lowered
      risks of (a) hospitalization for HF and (b) the combined endpoint of
      cardiovascular mortality and hospitalization for HF at 1 year, in patients with
      HF and preserved LVEF. However, they have no significant effect on mortality
      during more prolonged follow-up; the width of the 95% confidence limits is
      compatible with a benefit as big as 10% or a hazard as large as 13%.

PMID- 21193682
TI  - The need for increased utilization of statins after occlusive stroke.
AB  - In registry data, among patients who have survived an occlusive stroke, only
      about half are treated with statins despite a large and persuasive totality of
      evidence, which includes large-scale randomized trials. In a comprehensive
      worldwide meta-analysis of 90,056 participants, statins conferred statistically
      significant and clinically important reductions in stroke and myocardial
      infarction, as well as cardiovascular and total mortality. In the Stroke
      Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial of
      patients with prior stroke or transient ischemic attack, high-potency statins
      decreased risks of recurrent stroke and major cardiovascular events. In a
      nonrandomized subgroup analysis, patients who achieved a 50% or greater reduction
      in low-density lipoprotein cholesterol (LDL-C) compared to those who achieved
      <50% had a statistically significant 31% reduction in risk of stroke. Finally, in
      a comprehensive, worldwide meta-analysis of all trials of cardiovascular disease,
      patients treated with intensive compared with conventional statin therapy had
      significantly reduced risks of stroke and myocardial infarction as well as any
      cardiovascular event or death. Based on this totality of evidence the US federal
      guidelines as well as those of the American Heart Association/American Stroke
      Association have been revised to recommend that patients with a prior occlusive
      stroke should have an optional goal for LDL of 70 mg/dL. All these considerations
      pose important and timely clinical and public health challenges concerning the
      need for wider utilization of statins in the treatment of patients with stroke.

PMID- 21193683
TI  - First direct comparison of the late sodium current blocker ranolazine to
      established antiarrhythmic agents in an ischemia/reperfusion model.
AB  - INTRODUCTION: There are few safe antiarrhythmics for ischemic heart disease.
      Whereas ranolazine is a promising late INa blocker with antiarrhythmic effects,
      and devoid of pro-arrhythmic properties, there are no direct comparisons between
      ranolazine and other antiarrhythmic agents in an ischemia/reperfusion setting.
      HYPOTHESIS AND METHODS: To determine whether ranolazine was as effective as
      sotalol and lidocaine to reduce ischemia/reperfusion-induced arrhythmias,
      anesthetized rats were subjected to 5 minutes of proximal left coronary artery
      occlusion plus 5 minutes of reperfusion, which causes severe ventricular
      arrhythmias. At 21 minutes prior to coronary occlusion, rats (n = 20 per group)
      were randomized to receive either sotalol (intravenous [IV] bolus 5 mg/kg, 10
      mg/kg per hour infusion), lidocaine (IV bolus 2.5 mg/kg, 2.5 mg/kg/hr infusion),
      ranolazine (IV bolus 3.3 mg/kg, 3.2 mg/kg per hour infusion), or saline
      (control). RESULTS: The incidence of ventricular arrhythmias in the sotalol (S),
      lidocaine (L), ranolazine (R), and control (C) groups was 7/20, 10/20, 9/20, and
      16/20, respectively (P = .01 S vs C, P = .10 L vs C, and P = .048 R vs C).
      Duration of ventricular tachycardia (VT) episodes was reduced from 15.5 seconds
      (mean) in C to 1.3 seconds in S, 1.4 sec in L and 0.09 sec in R (P < .05 for S vs
      C and R vs C by Wilcoxon test). The number of rats with any (>= 10 seconds)
      sustained VT was 3 in C versus 1, 0, and 0 in the S, L, and R groups,
      respectively. Two rats in C had reversible ventricular fibrillation versus 0 in
      the S, L, and R groups. The number of ventricular premature beats (VPBs) per rat
      was 10.9 in C, 2.3 in S, 4.9 in L, and 5.7 in R (P < .05 for S, L, or R vs C). P
      = NS for R versus L or S for all analyses. CONCLUSION: In this first head-to-head
      comparison of R vs other antiarrhythmic agents at therapeutic doses in an
      ischemia/reperfusion model, ranolazine (which lacks pro-arrhythmic effects) was
      as effective as either sotalol or lidocaine to reduce reperfusion-induced
      ventricular arrhythmias.

PMID- 21193685
TI  - Troponins: redefining their limits.
AB  - The diagnosis of myocardial infarction (MI) depends on a rise and/or fall of
      cardiac biomarkers such as troponins in the appropriate clinical context.
      Conventional troponin assays lack sensitivity and precision at the low serum
      concentrations observed in the early hours after the onset of chest pain. New,
      highly sensitive troponin assays may offer improved certainty in these early
      hours. Many of these assays can detect troponins reliably at serum concentrations
      that occur in patients with chronic stable heart disease and even in asymptomatic
      healthy individuals. Indiscriminate use of these previously undetectable
      concentrations for the early diagnosis of acute MI will be accompanied by reduced
      specificity. However, they are likely to improve risk stratification of patients
      with chronic heart disease. This review focuses on the available highly sensitive
      troponin assays and their likely use in the diagnosis of acute MI and risk
      stratification of patients with heart disease.

PMID- 21193684
TI  - Associations of vitamin D, parathyroid hormone and calcium with cardiovascular
      risk factors in US adolescents.
AB  - OBJECTIVE: To examine independent associations of serum 25-hydroxyvitamin D
      (25(OH)D), parathyroid hormone (PTH) and calcium with a range of cardiovascular
      risk factors in adolescents. DESIGN: Cross-sectional population-based study.
      SETTING: A nationally representative sample of the US adolescent population.
      PARTICIPANTS: Healthy adolescents (aged 12-19) participating in the National
      Health and Nutrition Examination Survey (NHANES) between 2001 and 2006. Numbers
      varied between 740 and 5609 for given exposure and outcome associations. MAIN
      OUTCOME MEASURES: Systolic blood pressure (SBP), diastolic blood pressure (DBP),
      lipids (triglycerides, low-density lipoprotein cholesterol (LDL-C) and high
      density lipoprotein cholesterol (HDL-C)), fasting insulin and glucose, postload
      glucose and glycohaemoglobin (HbA1c). RESULTS: 25(OH)D was inversely associated
      with SBP (-0.068 standard deviations (SD), 95% CI -0.118 to -0.018), and
      positively associated with HDL-C (0.101; 0.040 to 0.162) and HbA1c (0.073; 0.021
      to 0.125) after adjustment for gender, age, ethnicity, socioeconomic status and
      waist circumference. In adjusted models, PTH was inversely associated with
      triglycerides (-0.115; -0.188 to -0.042) and LDL-C (-0.133; -0.207 to -0.060). In
      adjusted models, calcium was positively associated with fasting insulin (0.110;
      0.060 to 0.160), postload glucose (0.116; 0.000 to 0.232), HbA1c (0.079; 0.035 to
      0.123), triglycerides (0.182; 0.122 to 0.242), HDL-C (0.049; 0.010 to 0.088) and
      LDL-C (0.137; 0.080 to 0.195). The associations of each exposure with risk
      factors remained after mutual adjustment for each other. CONCLUSION: Higher
      calcium levels might be a more important predictor of increased cardiovascular
      risk in adolescents than lower 25(OH)D levels or PTH levels, but the findings
      require replication in additional studies and examination in prospective studies.

PMID- 21193686
TI  - Resting global and regional left ventricular contractility in patients with heart
      failure and normal ejection fraction: insights from speckle-tracking
      echocardiography.
AB  - OBEJCTIVE: To compare left ventricular (LV) systolic performance and
      contractility in patients with heart failure and normal ejection fraction
      (HFNEF), compared with patients with heart failure and reduced ejection fraction
      (HFREF) and healthy subjects using newer echocardiographic techniques. DESIGN: A
      case-control trial. SETTING: University teaching hospital (tertiary referral
      centre). PATIENTS: Sixty healthy control subjects (53 +/- 10 years), 112 patients
      with HFNEF (74 +/- 12 years) and 175 patients with HFREF (67 +/- 13 years).
      INTERVENTIONS: All underwent standard two-dimensional, Doppler and speckle
      tracking echocardiography. MAIN OUTCOME MEASURES: Effective arterial (Ea) and LV
      end-systolic elastance (Ees), stress-corrected mid-wall shortening, preload
      recruitable stroke work, two-dimensional strain and torsion. Comparisons were
      adjusted for age, gender and body size. RESULTS: Besides diastolic dysfunction,
      patients with HFNEF had impaired load-independent ventricular contractility with
      a progressive decrease of the corrected Ees from controls (2.9 +/- 0.8 mm Hg/g)
      to HFNEF (2.2 +/- 0.9 mm Hg/g) followed by HFREF (0.8 +/- 0.3 mm Hg/g; all
      p<0.001). Ventricular-arterial coupling ratio was preserved in the HFNEF subgroup
      (normal 0.48 +/- 0.09 vs 0.65 +/- 0.16; p = NS) at the expense of both increased
      LV systolic stiffness and Ea. In addition, there was progressive decrease of
      global 2D circumferential, radial and longitudinal strain as well as torsion from
      normal, HFNEF to HFREF groups, even after adjustment for LV end-systolic wall
      stress or end-diastolic volume (all p<0.01). About 50% of patients with HFNEF had
      >= 1 global strain or torsion parameter depressed below normal after correction
      for LV end-systolic wall stress, with >85% falling below their corresponding
      stress-corrected mean. CONCLUSIONS: Impaired myocardial contractility is evident
      in many patients with HFNEF and this may contribute towards pathophysiology of
      HFNEF more than previously thought.

PMID- 21193687
TI  - Assessing aortic strain and stiffness: don't forget the physics and engineering.

PMID- 21193688
TI  - Endothelium-dependent coronary vasomotor response and neointimal coverage of
      zotarolimus-eluting stents 3 months after implantation.
AB  - BACKGROUND: Zotarolimus-eluting stents (ZES) have a higher rate of neointimal
      coverage than the first-generation drug-eluting stents on optical coherence
      tomography (OCT). OBJECTIVE: To determine whether neointimal coverage of stent
      struts detected by OCT can be used as a surrogate for endothelial function after
      ZES implantation. DESIGN: Cross-sectional observational study. SETTING: Three
      months after ZES implantation. PATIENTS AND METHODS: OCT was performed in 20
      patients with a ZES at 3 months after stent implantation to evaluate strut
      coverage. Endothelium-dependent coronary vasomotion was estimated by infusing
      incremental doses of acetylcholine into the coronary ostium. The vascular
      response was measured in the 10&emsp14;mm segments proximal and distal to the
      stent. RESULTS: Of 20 ZES, 15 (75%) were covered completely with neointima, but
      the remaining 5 ZES had exposed struts. The high-dose acetylcholine infusion
      produced significant vasoconstriction in the proximal (-9.8+/-10.1%) and the
      distal stent segment (-29.7+/-22.7%). However, the degree of vasoconstriction to
      acetylcholine varied between individuals (from -0.6% to -77%). Although no
      relationship was observed between coronary vasomotor response (percentage change
      in diameter after acetylcholine administration) and average neointimal thickness,
      the number of cross-sections with uncovered struts showed an inverse correlation
      with coronary vasomotor response in proximal and distal stent segments (r=-0.57,
      p=0.007 and r=-0.83, p<0.001, respectively). CONCLUSIONS: The existence of
      exposed struts was associated with abnormal vasoconstriction to acetylcholine at
      3 months after ZES implantation. The findings suggest that complete neointimal
      coverage of stent struts assessed by OCT could be used as a surrogate for
      vasomotion impairment at 3 months after ZES implantation.

PMID- 21193690
TI  - Regional thicknesses and thickening of compacted and trabeculated myocardial
      layers of the normal left ventricle studied by cardiovascular magnetic resonance.
AB  - BACKGROUND: We used cardiovascular magnetic resonance (CMR) to study normal left
      ventricular (LV) trabeculation as a basis for differentiation from pathological
      noncompaction. METHODS AND RESULTS: The apparent end-diastolic (ED) and end
      systolic (ES) thicknesses and thickening of trabeculated and compacted myocardial
      layers were measured in 120 volunteers using a consistent selection of basal,
      mid, and apical CMR short-axis slices. All had a visible trabeculated layer in 1
      or more segments. The compacted but not the trabeculated layer was thicker in men
      than in women (P<0.01 at ED and ES). When plotted against age, the trabeculated
      and compacted layer thicknesses demonstrated opposite changes: an increase of the
      compact layer after the fourth decade at both ED and ES (P<0.05) but a decrease
      of the trabeculated layer. There was age-related preservation of total wall
      thickness at ED but an increase at ES (P<0.05). The compacted layer thickened,
      whereas the trabeculated layer thinned with systole, but neither change differed
      between sexes. With age, the most trabeculated LV segments showed significantly
      greater systolic thinning of trabeculated layers and, conversely, greater
      thickening of the compact segments (P<0.05). Total wall thickening is neither sex
      nor age dependent. There were no sex differences in the trabeculated/compacted
      ratio at ES or ED, but the ES trabeculated/compacted ratio was smaller in older
      (50 to 79 years) versus younger (20 to 49 years) groups (P<0.05). CONCLUSIONS: We
      demonstrated age- and sex-related morphometric differences in the apparent
      trabeculated and compacted layer thicknesses and systolic thinning of the visible
      trabeculated layer that contrasts with compacted myocardial wall thickening.

PMID- 21193691
TI  - Influence of diabetes mellitus on prognostic utility of imaging of myocardial
      sympathetic innervation in heart failure patients.
AB  - BACKGROUND: Patients with diabetes mellitus have accelerated progression of heart
      failure and often have impaired cardiac sympathetic innervation. The present
      study examines the implications for heart failure progression of cardiac
      sympathetic denervation, assessed by I-123 metaiodobenzylguanidine imaging, in
      diabetic compared with nondiabetic subjects. METHODS AND RESULTS: We evaluated
      343 diabetic and 618 nondiabetic subjects with New York Heart Association class
      II or III heart failure and a left ventricular ejection fraction <=35% over a
      median follow-up of 17 months. A multivariable Cox proportional hazards model was
      used to examine the influence of clinical variables, b-type natriuretic peptide,
      plasma norepinephrine, left ventricular ejection fraction, and I-123
      metaiodobenzylguanidine imaging parameters on time to a heart failure event. The
      late heart-to-mediastinum (H/M) ratio and the interaction term of diabetes
      mellitus with the prospectively selected late H/M ratio <1.6 were independent
      predictors of heart failure progression, providing incremental prognostic
      information beyond that available from all other variables. In diabetic subjects,
      late H/M ratio <1.6 was associated with a 2.99-fold greater 2-year rate of heart
      failure progression (33.5%) than late H/M ratio >=1.6 (11.2% event rate).
      CONCLUSIONS: The combination of diabetes mellitus and I-123
      metaiodobenzylguanidine H/M ratio is an independent predictor of heart failure
      progression, confirming the high risk of diabetic subjects with impaired cardiac
      sympathetic nerve function.

PMID- 21193693
TI  - Immune reconstitution is preserved in hematopoietic stem cell transplantation
      coadministered with regulatory T cells for GVHD prevention.
AB  - Recipient-specific regulatory T cells (rsTreg) can prevent graft-versus-host
      disease (GVHD) by inhibiting donor T-cell expansion after hematopoietic stem cell
      transplantation (HSCT) in mice. Importantly, in adult humans, because of thymus
      involution, immune reconstitution during the first months after HSCT relies on
      the peripheral expansion of donor T cells initially present in the graft.
      Therefore, we developed a mouse model of HSCT that excludes thymic output to
      study the effect of rsTreg on immune reconstitution derived from postthymic
      mature T cells present within the graft. We showed that GVHD prevention with
      rsTreg was associated with improvement of the limited immune reconstitution
      compared with GVHD mice in terms of cell numbers, activation phenotype, and
      cytokine production. We further demonstrated a preserved in vivo immune function
      using vaccinia infection and third-party skin-graft rejection models, suggesting
      that rsTreg immunosuppression was relatively specific of GVHD. Finally, we showed
      that rsTreg extensively proliferated during the first 2 weeks and then declined.
      In turn, donor Treg proliferated from day 15 on. Taken together, these results
      suggest that rsTreg GVHD prevention is associated with improved early immune
      reconstitution in a model that more closely approximates the biology of
      allogeneic HSCT in human adults.

PMID- 21193694
TI  - How I treat late effects in adults after allogeneic stem cell transplantation.
AB  - More than 25,000 allogeneic hematopoietic stem cell transplantations (allo-HCTs)
      are expected to be performed worldwide in 2010, a number that has been increasing
      yearly. With broadening indications, more options for allo-HCT, and improvement
      in survival, by 2020 there may be up to half a million long-term survivors after
      allo-HCT worldwide. These patients have increased risks for various late
      complications, which can cause morbidity and mortality. Most long-term survivors
      return to the care of their local hematologists/oncologists or primary care
      physicians, who may not be familiar with specialized monitoring recommendations
      for this patient population. The purpose of this article is to describe practical
      approaches to screening for and managing these late effects, with the goal of
      reducing preventable morbidity and mortality associated with allo-HCT.

PMID- 21193695
TI  - Induction of Ca2+-driven apoptosis in chronic lymphocytic leukemia cells by
      peptide-mediated disruption of Bcl-2-IP3 receptor interaction.
AB  - Bcl-2 contributes to the pathophysiology and therapeutic resistance of chronic
      lymphocytic leukemia (CLL). Therefore, developing inhibitors of this protein
      based on a thorough understanding of its mechanism of action is an active and
      promising area of inquiry. One approach centers on agents (eg, ABT-737) that
      compete with proapoptotic members of the Bcl-2 protein family for binding in the
      hydrophobic groove formed by the BH1-BH3 domains of Bcl-2. Another region of Bcl
      2, the BH4 domain, also contributes to the antiapoptotic activity of Bcl-2 by
      binding to the inositol 1,4,5-trisphosphate receptor (IP3R) Ca2(+) channel,
      inhibiting IP(3)-dependent Ca2(+) release from the endoplasmic reticulum. We
      report that a novel synthetic peptide, modeled after the Bcl-2-interacting site
      on the IP3R, binds to the BH4 domain of Bcl-2 and functions as a competitive
      inhibitor of the Bcl-2-IP3R interaction. By disrupting the Bcl-2-IP3R
      interaction, this peptide induces an IP3R-dependent Ca2(+) elevation in lymphoma
      and leukemia cell lines and in primary CLL cells. The Ca2(+) elevation evoked by
      this peptide induces apoptosis in CLL cells, but not in normal peripheral blood
      lymphocytes, suggesting the involvement of the Bcl-2-IP3R interaction in the
      molecular mechanism of CLL and indicating the potential merit of targeting this
      interaction therapeutically.

PMID- 21193696
TI  - Postrelapse survival in childhood acute lymphoblastic leukemia is independent of
      initial treatment intensity: a report from the Children's Oncology Group.
AB  - While intensification of therapy has improved event-free survival (EFS) and
      survival in newly diagnosed children with acute lymphoblastic leukemia (ALL),
      postrelapse outcomes remain poor. It might be expected that patients relapsing
      after inferior initial therapy would have a higher retrieval rate than after
      superior therapy. In the Children's Oncology Group Study CCG-1961, significantly
      superior EFS and survival were achieved with an augmented (stronger) versus
      standard intensity regimen of postinduction intensification (PII) for children
      with newly diagnosed high-risk ALL and rapid day 7 marrow response (EFS/survival
      81.2%/88.7% vs 71.7%/83.4%, respectively). This provided an opportunity to
      evaluate postrelapse survival (PRS) in 272 relapsed patients who had received
      randomly allocated initial treatment with augmented or standard intensity PII. As
      expected, PRS was worse for early versus late relapse, marrow versus
      extramedullary site, adolescent versus younger age and T versus B lineage.
      However, no difference in 3-year PRS was detected for having received augmented
      versus standard intensity PII (36.4% +/- 5.7% vs 39.2% +/- 4.1%; log rank P =
      .72). Similar findings were noted within subanalyses by timing and site of
      relapse, age, and immunophenotype. These findings provide insight into mechanisms
      of relapse in ALL, and are consistent with emergence of a resistant subclone that
      has acquired spontaneous mutations largely independent of initial therapy. This
      study is registered at www.clinicaltrials.gov as NCT00002812.

PMID- 21193699
TI  - Application of 3-dimensional ultrasonography in assessing carpal tunnel syndrome.
AB  - OBJECTIVES: The aim of study was to assess the usefulness of 3D ultrasonography
      (3DUS) in the diagnosis of carpal tunnel syndrome. METHODS: Fifty patients with
      carpal tunnel syndrome confirmed by electromyography and 37 healthy control
      participants underwent 3DUS of the wrists. The mean times per participant for the
      3DUS examination and review of the 3D volume set were recorded. The cross
      sectional area at the proximal carpal tunnel and the maximum swelling point were
      measured. Data from patients and controls were compared for determination of
      statistical significance. The accuracy of the 3DUS diagnostic criteria for carpal
      tunnel syndrome was evaluated using receiver operating characteristic analysis,
      and changes in the median nerve shape, including the maximum swelling point, were
      assessed by review of the 3D volume data. RESULTS: The mean times for examination
      of a participant and review in each wrist were 56 seconds and 5.7 minutes,
      respectively. Significant differences were observed in the mean cross-sectional
      areas of the median nerve between patients and controls. The mean cross-sectional
      areas +/- SD were 16.7 +/- 6.7 mm(2) in patients and 8.3 +/- 1.9 mm(2) in
      controls. Using the receiver operating characteristic curve, a cutoff value of
      greater than 10.5 mm(2) provided diagnostic sensitivity of 84% and specificity of
      86%. In 42 of 73 wrists with carpal tunnel syndrome, the median nerve showed
      fusiform morphologic abnormalities and maximum swelling points. CONCLUSIONS: Our
      results show that 3DUS could markedly decrease scanning time, and measurement of
      the median nerve cross-sectional area combined with morphologic analysis using
      3DUS is a promising supplementary method for the diagnosis of carpal tunnel
      syndrome.

PMID- 21193697
TI  - CD137 stimulation enhances the antilymphoma activity of anti-CD20 antibodies.
AB  - Antibody-dependent cell-mediated cytotoxicity (ADCC), which is largely mediated
      by natural killer (NK) cells, is thought to play an important role in the
      efficacy of rituximab, an anti-CD20 monoclonal antibody (mAb) used to treat
      patients with B-cell lymphomas. CD137 is a costimulatory molecule expressed on a
      variety of immune cells after activation, including NK cells. In the present
      study, we show that an anti-CD137 agonistic mAb enhances the antilymphoma
      activity of rituximab by enhancing ADCC. Human NK cells up-regulate CD137 after
      encountering rituximab-coated tumor B cells, and subsequent stimulation of these
      NK cells with anti-CD137 mAb enhances rituximab-dependent cytotoxicity against
      the lymphoma cells. In a syngeneic murine lymphoma model and in a
      xenotransplanted human lymphoma model, sequential administration of anti-CD20 mAb
      followed by anti-CD137 mAb had potent antilymphoma activity in vivo. These
      results support a novel, sequential antibody approach against B-cell malignancies
      by targeting first the tumor and then the host immune system.

PMID- 21193700
TI  - Epidermal cysts in the superficial soft tissue: sonographic features with an
      emphasis on the pseudotestis pattern.
AB  - OBJECTIVES: The purposes of this study were to report the sonographic features of
      superficial epidermal cysts with an emphasis on the characteristic pseudotestis
      appearance and to highlight the spectrum of ancillary findings. METHODS: The
      medical records and sonographic studies of all cases of surgically proven
      epidermal cysts (n = 42) from January 2005 through December 2009 were reviewed.
      Twenty-six epidermal cysts (62%) that appeared on sonography as ovoid nodules
      with homogeneous low to medium echoes, simulating a testicle, were included in
      the pseudotestis group. The other 16 epidermal cysts (38%) without the
      pseudotestis pattern were included in the nonpseudotestis group. The age, sex,
      lesion size, length to width ratio, sonographic appearances, and frequencies of
      rupture and infection were compared between the groups. RESULTS: Epidermal cysts
      in the nonpseudotestis group presented as heterogeneously echoic or lobulated
      nodules or had a concentric ring or target appearance. There were no significant
      differences in the age, sex, lesion size, and length to width ratio between the
      groups. The pseudotestis group had significantly higher frequencies of
      intralesional bright echogenic reflectors and filiform anechoic areas than the
      nonpseudotestis group (P < .01). There were no significant differences in the
      associated ancillary sonographic features, including posterior acoustic
      enhancement, dermal attachment, focal dermal protrusion, and frequencies of
      rupture and infection between the groups. CONCLUSIONS: In this study, two-thirds
      of the superficial epidermal cysts had a characteristic pseudotestis pattern on
      sonography, whereas the others could be suspected by recognition of the ancillary
      sonographic findings, including dermal attachment and focal dermal protrusion or
      a distinctive concentric ring or target pattern.

PMID- 21193701
TI  - Ultrasound is safe... right?: resident and maternal-fetal medicine fellow
      knowledge regarding obstetric ultrasound safety.
AB  - OBJECTIVES: This study was created to assess the knowledge levels of postgraduate
      year 4 obstetrics and gynecology residents and maternal-fetal medicine fellows in
      the United States regarding the safety of obstetric ultrasound and the use of the
      output display standard. METHODS: An electronic survey was submitted to each
      Accreditation Council for Graduate Medical Education-accredited obstetrics and
      gynecology residency and each maternal-fetal medicine fellowship program in the
      United States over 2 academic years from 2008 to 2010. RESULTS: A total of 165
      surveys were completed (67 by postgraduate year 4 obstetrics and gynecology
      residents and 92 by maternal-fetal medicine fellows). In total, 13.4% of
      residents and 20.9% of maternal-fetal medicine fellows knew how to find or use
      the output display standard, and 10.9% of residents and 22.7% of fellows reported
      use of the output display standard during their ultrasound examinations. Overall,
      37% to 46% of residents and fellows reported no limitations to the use of
      obstetric ultrasound and 22% to 39% reported no limitations to the use of Doppler
      ultrasound in the first, second, and third trimesters. Maternal-fetal medicine
      fellow knowledge of ultrasound safety generally improved with each year of
      training; however, only 34.8% of third-year fellows reported use of the output
      display standard. CONCLUSIONS: Currently, obstetrics and gynecology resident
      knowledge of obstetric ultrasound safety is low. Maternal-fetal medicine fellow
      knowledge is stronger overall; however, few are using the output display standard
      routinely in their last year of fellowship training. This study provides evidence
      of the need for improved education on the subject of obstetric ultrasound safety.

PMID- 21193702
TI  - Irregular yolk sac shape: is it really associated with an increased risk of
      spontaneous abortion?
AB  - OBJECTIVES: The yolk sac is the first conceptional structure that becomes
      sonographically visible within the gestational sac. Because the yolk sac is the
      primary route of exchange between the embryo and the mother, it is essential in
      early embryonic life. This study aimed to determine whether an irregular yolk sac
      shape is associated with an increased risk of spontaneous abortion. METHODS: The
      shape and size of the yolk sac were assessed by transvaginal sonography in 183
      women who had normal and healthy pregnancies with gestational ages of 6 to 8
      weeks. RESULTS: Most of the embryos had a yolk sac with a regular shape (152 of
      183 [83%]), whereas the remaining embryos had a yolk sac with an irregular shape
      (31 of 183 [17%]). Although there was a trend toward a lower rate of irregular
      yolk sacs with advancing gestational age, the difference was not statistically
      significant (P = .13). Spontaneous abortion occurred in 6 of 183 pregnancies
      (3.3%): 1 of the 31 (3.2%) with an irregular yolk sac shape and 5 of the 152
      (3.3%) with a regular yolk sac shape. The rates of spontaneous abortion were
      statistically similar for pregnancies with a regular yolk sac shape and those
      with an irregular shape (P > .99). CONCLUSIONS: This study suggests that an
      irregular yolk sac shape is unrelated to an increased risk of spontaneous
      abortion.

PMID- 21193703
TI  - Sonographic depiction of the fetal anus and its utility in the diagnosis of
      anorectal malformations.
AB  - OBJECTIVES: The purpose of this study was to describe the sonographic appearance
      of the fetal anus and its usefulness in diagnosis of anal atresia. METHODS: An
      anomaly scan was performed in 13,150 patients over 8 years. Gestational ages
      ranged from 16 to 38 weeks. A tangential scan of the fetal perineum was
      performed. The anus was seen as a hypoechoic ring representing the wall of the
      anal canal with a central echogenic dot representing the lumen. This appearance
      was seen posterior to the external genitalia. If there was failure to see this
      appearance, a coronal scan of the fetal pelvis was done to look for the anal
      canal in contiguity with the rectum and to confirm its extension up to perineum.
      Failure to see these two features was considered diagnostic of anal atresia.
      RESULTS: On the basis of these criteria, anal atresia was diagnosed in 17
      fetuses. Sixteen of these fetuses also had other associated anomalies. The
      appearance of the anus was useful for ruling out anal atresia in 2 fetuses with a
      dilated colon containing echogenic meconium balls. CONCLUSIONS: The anus is
      visible on a tangential scan of the fetal perineum. It can be seen routinely
      during an anomaly scan to diagnose or rule out anal atresia.

PMID- 21193704
TI  - Assessment of corpus callosum biometric measurements at 18 to 32 weeks' gestation
      by 3-dimensional sonography.
AB  - OBJECTIVES: The purposes of this study were to construct reference limits for
      corpus callosum dimensions measured on images reconstructed from 3-dimensional
      (3D) sonography and to evaluate the reproducibility of these measurements.
      METHODS: Three-dimensional sonographic volumes were acquired transabdominally
      from an axial view of the head in 361 fetuses cross-sectionally studied at 18 to
      32 weeks' gestation. Offline analysis of the fetal brain midsagittal plane was
      used to evaluate the length and area of the corpus callosum and corpus callosum
      cavum septi pellucidi complex. The agreement between 2-dimensional (2D) and 3D
      measurements as well as the interobserver variability in 3D measurements were
      assessed by interclass correlation coefficients (ICCs). RESULTS: Adequate
      visualization of the midsagittal plane was obtained in 98.1% of the fetuses. A
      clear distinction between the corpus callosum and cavum septi pellucidi was
      obtained in 35.7% of the fetuses, whereas in the remaining cases, the corpus
      callosum-cavum septi pellucidi complex was visualized as a single echogenic
      structure. The corpus callosum-cavum septi pellucidi complex length (r = 0.806; P
      < .0001), corpus callosum-cavum septi pellucidi complex area (r = 0.920; P <
      .0001), and corpus callosum area (r = 0.713; P < .0001) showed a significant
      linear growth with gestation. A good agreement was found between measurements
      from both 2D and 3D sonographic views (corpus callosum length ICC, 0.916) as well
      as between measurements obtained by different observers (corpus callosum-cavum
      septi pellucidi complex length ICC, 0.936; corpus callosum-cavum septi pellucidi
      complex area ICC, 0.931). CONCLUSIONS: Measurements of the corpus callosum and
      cavum septi pellucidi can be obtained from the midsagittal plane of the fetal
      brain reconstructed from 3D volumes acquired transabdominally. The constructed
      nomograms may facilitate the diagnosis of corpus callosum abnormalities.

PMID- 21193705
TI  - Early biometric lag in the prediction of small for gestational age neonates and
      preeclampsia.
AB  - OBJECTIVE: An early fetal growth lag may be a marker of future complications. We
      sought to determine the utility of early biometric variables in predicting
      adverse pregnancy outcomes. METHODS: In this retrospective cohort study, the
      crown-rump length at 11 to 14 weeks and the head circumference, biparietal
      diameter, abdominal circumference, femur length, humerus length, transverse
      cerebellar diameter, and estimated fetal weight at 18 to 24 weeks were converted
      to an estimated gestational age using published regression formulas. Sonographic
      fetal growth (difference between each biometric gestational age and the crown
      rump length gestational age) minus expected fetal growth (number of days elapsed
      between the two scans) yielded the biometric growth lag. These lags were tested
      as predictors of small for gestational age (SGA) neonates (<=10th percentile) and
      preeclampsia. RESULTS: A total of 245 patients were included. Thirty-two (13.1%)
      delivered an SGA neonate, and 43 (17.6%) had the composite outcome. The head
      circumference, biparietal diameter, abdominal circumference, and estimated fetal
      weight lags were identified as significant predictors of SGA neonates after
      adjusted analyses (P < .05). The addition of either the estimated fetal weight or
      abdominal circumference lag to maternal characteristics alone significantly
      improved the performance of the predictive model, achieving areas under the curve
      of 0.72 and 0.74, respectively. No significant association was found between the
      biometric lag variables and the development of preeclampsia. CONCLUSIONS:
      Routinely available biometric data can be used to improve the prediction of
      adverse outcomes such as SGA. These biometric lags should be considered in
      efforts to develop screening algorithms for adverse outcomes.

PMID- 21193706
TI  - Frequency-dependent evaluation of the role of definity in producing sonoporation
      of Chinese hamster ovary cells.
AB  - OBJECTIVES: Sonoporation uses ultrasound (US) and ultrasound contrast agents
      (UCAs) to enhance cell permeabilization, thereby allowing delivery of therapeutic
      compounds non-invasively into specific target cells. The objective of this study
      was to elucidate the biophysical mechanism of sonoporation, specifically the role
      of UCAs as well as exposure frequency. The inertial cavitation (IC) thresholds of
      the lipid-shelled octafluoropropane UCA were directly compared to the levels of
      generated sonoporation to determine the involvement of UCAs in producing
      sonoporation. METHODS: Chinese hamster ovary cells were exposed as a monolayer in
      a solution of the UCA, 500,000-Da fluorescein isothiocyanate-dextran, and
      phosphate-buffered saline to 30 seconds of pulsed US (pulse duration, 5 cycles;
      pulse repetition frequency, 10 Hz) at 3 frequencies (0.92, 3.2, and 5.6 MHz). The
      peak rarefactional pressure (P(r)) was varied over a range from 4 kPa to 4.1 MPa,
      and 5 to 7 independent replicates were performed at each pressure. RESULTS: The
      experimental observations demonstrated that IC was likely not the physical
      mechanism for sonoporation. Sonoporation activity was observed at pressure levels
      below the threshold for IC of the UCA (1.27 +/- 0.32 MPa at 0.92 MHz, 0.84 +/-
      0.19 MPa at 3.2 MHz, and 2.57 +/- 0.26 MPa at 5.6 MHz) for all 3 frequencies
      examined. The P(r) values at which the peak sonoporation activity occurred were
      1.4 MPa at 0.92 MHz, 0.25 MPa at 3.2 MHz, and 2.3 MPa at 5.6 MHz. The UCA
      collapse thresholds followed a similar trend. A 1-way analysis of variance test
      confirmed that sonoporation activity differed among the 3 frequencies examined (P
      = 10(-8)). CONCLUSIONS: These results thus suggest that sonoporation is related
      to linear and/or nonlinear oscillation of the UCA occurring at pressure levels
      below the IC threshold.

PMID- 21193707
TI  - Speckle-tracking echocardiography: a new technique for assessing myocardial
      function.
AB  - Speckle-tracking echocardiography has recently emerged as a quantitative
      ultrasound technique for accurately evaluating myocardial function by analyzing
      the motion of speckles identified on routine 2-dimensional sonograms. It provides
      non-Doppler, angle-independent, and objective quantification of myocardial
      deformation and left ventricular systolic and diastolic dynamics. By tracking the
      displacement of the speckles during the cardiac cycle, strain and the strain rate
      can be rapidly measured offline after adequate image acquisition. Data regarding
      the feasibility, accuracy, and clinical applications of speckle-tracking
      echocardiography are rapidly accumulating. This review describes the fundamental
      concepts of speckle-tracking echocardiography, illustrates how to obtain strain
      measurements using this technique, and discusses their recognized and developing
      clinical applications.

PMID- 21193708
TI  - Parametric imaging using subharmonic signals from ultrasound contrast agents in
      patients with breast lesions.
AB  - Parametric maps showing perfusion of contrast media can be useful tools for
      characterizing lesions in breast tissue. In this study we show the feasibility of
      parametric subharmonic imaging (SHI), which allows imaging of a vascular marker
      (the ultrasound contrast agent) while providing near complete tissue suppression.
      Digital SHI clips of 16 breast lesions from 14 women were acquired. Patients were
      scanned using a modified LOGIQ 9 scanner (GE Healthcare, Waukesha, WI)
      transmitting/receiving at 4.4/2.2 MHz. Using motion-compensated cumulative
      maximum intensity (CMI) sequences, parametric maps were generated for each lesion
      showing the time to peak (TTP), estimated perfusion (EP), and area under the time
      intensity curve (AUC). Findings were grouped and compared according to biopsy
      results as benign lesions (n = 12, including 5 fibroadenomas and 3 cysts) and
      carcinomas (n = 4). For each lesion CMI, TTP, EP, and AUC parametric images were
      generated. No significant variations were detected with CMI (P = .80), TTP (P =
      .35), or AUC (P = .65). A statistically significant variation was detected for
      the average pixel EP (P = .002). Especially, differences were seen between
      carcinoma and benign lesions (mean +/- SD, 0.10 +/- 0.03 versus 0.05 +/- 0.02
      intensity units [IU]/s; P = .0014) and between carcinoma and fibroadenoma (0.10
      +/- 0.03 versus 0.04 +/- 0.01 IU/s; P = .0044), whereas differences between
      carcinomas and cysts were found to be nonsignificant. In conclusion, a parametric
      imaging method for characterization of breast lesions using the high contrast to
      tissue signal provided by SHI has been developed. While the preliminary sample
      size was limited, results show potential for breast lesion characterization based
      on perfusion flow parameters.

PMID- 21193709
TI  - Satisfactory rate of postprocessing visualization of standard fetal cardiac views
      from 4-dimensional cardiac volumes acquired during routine ultrasound practice by
      experienced sonographers in peripheral centers.
AB  - The aim of this study was to evaluate the feasibility of visualizing standard
      cardiac views from 4-dimensional (4D) cardiac volumes obtained at ultrasound
      facilities with no specific experience in fetal echocardiography. Five
      sonographers prospectively recorded 4D cardiac volumes starting from the 4
      chamber view on 500 consecutive pregnancies at 19 to 24 weeks' gestation
      undergoing routine ultrasound examinations (100 pregnancies for each
      sonographer). Volumes were sent to the referral center, and 2 independent
      reviewers with experience in 4D fetal echocardiography assessed their quality in
      the display of the abdominal view, 4-chamber view, left and right ventricular
      outflow tracts, and 3-vessel and trachea view. Cardiac volumes were acquired in
      474 of 500 pregnancies (94.8%). The 2 reviewers respectively acknowledged the
      presence of satisfactory images in 92.4% and 93.6% of abdominal views, 91.5% and
      93.0% of 4-chamber views, in 85.0% and 86.2% of left ventricular outflow tracts,
      83.9% and 84.5% of right ventricular outflow tracts, and 85.2% and 84.5% of 3
      vessel and trachea views. The presence of a maternal body mass index of greater
      than 30 altered the probability of achieving satisfactory cardiac views, whereas
      previous maternal lower abdominal surgery did not affect the quality of
      reconstructed cardiac views. In conclusion, cardiac volumes acquired by 4D
      sonography in peripheral centers showed high enough quality to allow satisfactory
      diagnostic cardiac views.

PMID- 21193710
TI  - Spontaneous intratesticular hemorrhage: two case descriptions and brief review of
      the literature.
AB  - Spontaneous intratesticular hemorrhage is an extremely rare entity with few prior
      reports in the literature. Although intratesticular hemorrhage in the setting of
      trauma or malignancy is common, spontaneous intratesticular hemorrhage has no
      identifiable risk factors. The sonographic appearance of spontaneous
      intratesticular hemorrhage poses a diagnostic dilemma because of its similarity
      to testicular malignancy. We present 2 cases of spontaneous intratesticular
      hemorrhage that were confirmed after unilateral orchiectomy and histologic
      examination.

PMID- 21193711
TI  - Embryonal rhabdomyosarcoma of the tunica dartos in the scrotum.
AB  - We report 2 cases of embryonal rhabdomyosarcoma, a rare malignant tumor, arising
      from the tunica dartos in the scrotum. Sonography revealed that each tumor had
      clear boundaries, a complete capsule, abundant blood flow, and an internal
      hypoechoic signal. Patients with embryonal rhabdomyosarcoma who have suspected
      lymph node metastases or distant metastatic lesions should undergo computed
      tomography. Our 2 cases were confirmed by subsequent histopathologic diagnosis
      and immunohistochemical staining with desmin and myogenin. The 2 patients were
      treated surgically with radical excisions and chemotherapy but without
      radiotherapy. To our knowledge, no cases of embryonal rhabdomyosarcoma
      originating from the scrotal tunica dartos have previously been reported in the
      medical literature.

PMID- 21193712
TI  - Sonographic findings in groove pancreatitis.
AB  - Groove pancreatitis is a rare form of chronic pancreatitis involving the anatomic
      plane between the pancreatic head and duodenum. The radiographic diagnosis
      remains challenging, and most patients undergo exploratory laparotomy on
      suspicion of a periampullary malignancy. The appearance of groove pancreatitis on
      transabdominal and intraoperative sonography has rarely been reported in the
      literature. The sonographic findings in our 2 patients included a hypoechoic thin
      area between the pancreatic head and duodenum, a hyperechoic and thickened wall
      of the adjacent duodenum, and a heterogeneous or hyperechoic dorsocranial part of
      the pancreatic head.

PMID- 21193713
TI  - Lipoma arborescens in the bicipitoradial bursa of the elbow: sonographic
      findings.

PMID- 21193714
TI  - Use of the double decidual sac sign and intradecidual sign.

PMID- 21193715
TI  - AIUM practice guideline for the performance of diagnostic and screening
      ultrasound examinations of the abdominal aorta in adults.

PMID- 21193716
TI  - AIUM practice guideline for the performance of fetal echocardiography.

PMID- 21193717
TI  - AIUM practice guideline for the performance of peripheral arterial ultrasound
      examinations using color and spectral Doppler imaging.

PMID- 21193718
TI  - Practice guideline for the performance of peripheral venous ultrasound
      examinations.

PMID- 21193719
TI  - AIUM practice guideline for the performance of scrotal ultrasound examinations.

PMID- 21193720
TI  - AIUM practice guideline for the performance of ultrasound evaluation of the
      prostate (and surrounding structures).

PMID- 21193721
TI  - RETRACTION: Reply to Editorial Comment Regarding "X:Y Sperm Ratio in Boron
      Exposed Men," by Robbins et al. 2008.
AB  - The Editorial Response listed above, which did not appear in the print journal,
      was retracted by the Editors of the Journal of Andrology with the consent of the
      authors because the significant delay in processing the Editorial Response has
      rendered the information contained in it not currently relevant. The Editors
      extend their apologies to the authors and to the scientific community.

PMID- 21193722
TI  - Androgen receptor CAG repeat polymorphism is not associated with erectile
      dysfunction complaints, gonadal steroids, and sleep parameters: data from a
      population-based survey.
AB  - Erectile dysfunction (ED) can be affected by androgen levels, which exert their
      action through the androgen receptor (AR). Androgenic action has been
      demonstrated to inversely correlate with a polymorphic trinucleotide CAG repeat
      region in the AR gene. We conducted an epidemiologic study to determine the
      potential association between the CAG repeat polymorphism of the AR gene and ED
      complaints, gonadal steroids, and sleep parameters in a large population-based
      sample in Sao Paulo, Brazil. AR CAG repeat was genotyped in 79 men with ED
      complaints and in 340 controls. Sleep and hormonal profiles were measured in all
      men. There was no association between the AR CAG repeat polymorphism and ED
      complaints. Moreover, there was no significant correlation among free and total
      testosterone, estradiol, follicle-stimulating hormone, and luteinizing hormone
      levels, as well as sleep parameters with the CAG repeat length, when evaluating
      the population as a whole, as well as subdivided into ED and control groups
      independently. The results were not affected when the data were analyzed in
      quartiles, divided by the median of the sample, or after correction for
      population stratification. AR CAG repeat polymorphism is not associated with ED
      complaints, gonadal steroids, and sleep parameters in men from a population-based
      sample in Brazil.

PMID- 21193723
TI  - RETRACTION:Editorial Comment Regarding "X:Y Sperm Ratio in Boron Exposed Men," by
      Robbins et al. 2008.
AB  - The Editorial Comment listed above, which did not appear in the print journal,
      was retracted by the Editors of the Journal of Andrology with the consent of the
      authors because the significant delay in processing the Editorial Comment has
      rendered the information contained in it not currently relevant. The Editors
      extend their apologies to the authors and to the scientific community.

PMID- 21193724
TI  - A continuous-index Bayesian hidden Markov model for prediction of nucleosome
      positioning in genomic DNA.
AB  - Nucleosomes are units of chromatin structure, consisting of DNA sequence wrapped
      around proteins called "histones." Nucleosomes occur at variable intervals
      throughout genomic DNA and prevent transcription factor (TF) binding by blocking
      TF access to the DNA. A map of nucleosomal locations would enable researchers to
      detect TF binding sites with greater efficiency. Our objective is to construct an
      accurate genomic map of nucleosome-free regions (NFRs) based on data from high
      throughput genomic tiling arrays in yeast. These high-volume data typically have
      a complex structure in the form of dependence on neighboring probes as well as
      underlying DNA sequence, variable-sized gaps, and missing data. We propose a
      novel continuous-index model appropriate for non-equispaced tiling array data
      that simultaneously incorporates DNA sequence features relevant to nucleosome
      formation. Simulation studies and an application to a yeast nucleosomal assay
      demonstrate the advantages of using the new modeling framework, as well as its
      robustness to distributional misspecifications. Our results reinforce the
      previous biological hypothesis that higher-order nucleotide combinations are
      important in distinguishing nucleosomal regions from NFRs.

PMID- 21193725
TI  - Comment on: Kim et al. (2010) Hypothalamic Angptl4/Fiaf is a novel regulator of
      food intake and body weight. Diabetes;59:2772-2780.

PMID- 21193727
TI  - Comment on: Kaiyala et al. (2010) Identification of body fat mass as a major
      determinant of metabolic rate in mice. Diabetes;59:1657-1666.

PMID- 21193729
TI  - Comment on: Matsushita et al. (2010) The association of hemoglobin A1c with
      incident heart failure among people without diabetes: The atherosclerosis risk in
      communities study. Diabetes;59:2020-2026.

PMID- 21193731
TI  - Comment on: Lin et al. (2010) Immune cell-derived C3 is required for autoimmune
      diabetes induced by multiple low doses of streptozotocin. Diabetes;59: 2247-2252.

PMID- 21193733
TI  - Stopping type 1 diabetes: attempts to prevent or cure type 1 diabetes in man.

PMID- 21193734
TI  - Diabetic retinopathy: targeting vasoregression.

PMID- 21193735
TI  - Toward a more complete (and less controversial) understanding of energy
      expenditure and its role in obesity pathogenesis.

PMID- 21193737
TI  - TRP-ing down the path to insulin secretion.

PMID- 21193736
TI  - Elimination of hypoglycemia from the lives of people affected by diabetes.

PMID- 21193738
TI  - Wnt4/beta-catenin signaling induces VSMC proliferation and is associated with
      intimal thickening.
AB  - RATIONALE: Vascular smooth muscle cell (VSMC) proliferation causes intimal
      thickening in atherosclerosis and restenosis. Previously, we demonstrated that
      Wnt/beta-catenin signaling upregulates VSMC proliferation in vitro. OBJECTIVE: We
      examined this pathway in vivo and investigated the involvement of specific Wnt
      proteins in VSMC proliferation. METHODS AND RESULTS: Left carotid arteries of
      TOPgal (beta-catenin signaling reporter) transgenic mice were ligated to induce
      intimal thickening. beta-Catenin signaling was induced in the media and intima at
      3 and 28 days after ligation, respectively, and was associated with VSMC
      proliferation and cyclin D1 expression. In vitro, a Wnt agonist promoted mouse
      VSMC proliferation, whereas Wnt inhibitory factor (WIF)-1 retarded platelet
      derived growth factor-BB (PDGF-BB)-induced VSMC proliferation. Microarray
      analysis and quantitative PCR detected a significant induction of Wnt2 and Wnt4
      mRNA in PDGF-BB-treated (proliferating) VSMCs compared to quiescent VSMCs.
      Western blotting revealed this increase was only translated into protein for
      Wnt4. Specific silencing RNA knockdown of Wnt4, but not Wnt2, significantly
      reduced VSMC proliferation. Recombinant Wnt4, but not Wnt2, significantly
      increased VSMC proliferation by ~2-fold and silencing RNA knockdown revealed this
      is via Frizzled 1. Immunohistochemistry showed that increased Wnt4 protein
      correlated with VSMC proliferation and cyclin D1 expression (P<0.05 and P<0.001,
      respectively) during intimal thickening after rat carotid artery injury.
      Importantly, we also showed that intimal thickening and VSMC proliferation after
      carotid artery ligation was significantly retarded in Wnt4(+/-) compared to
      Wnt4(+/+) mice. CONCLUSIONS: This study demonstrates that Wnt/beta-catenin
      signaling occurs in proliferating VSMCs during intimal thickening and indicates
      that this is a result of Wnt4 upregulation.

PMID- 21193739
TI  - Simultaneous measurement of protein oxidation and S-nitrosylation during
      preconditioning and ischemia/reperfusion injury with resin-assisted capture.
AB  - RATIONALE: Redox modifications play an important role in many cellular processes,
      including cell death. Ischemic preconditioning (IPC) has been shown to involve
      redox signaling. Protein S-nitrosylation (SNO) is increased following myocardial
      IPC, and SNO is thought to provide cardioprotection, in part, by reducing
      cysteine oxidation during ischemia/reperfusion (IR) injury. OBJECTIVE: To test
      the hypothesis that SNO provides cardioprotection, in part, by shielding against
      cysteine oxidation following IR injury. METHODS AND RESULTS: We developed a new
      method to measure protein oxidation using resin-assisted capture (Ox-RAC), which
      is similar to the SNO-RAC method used in the quantification of SNO. Langendorff
      perfused hearts were subjected to various perfusion protocols (control, IPC, IR,
      IPC-IR, IPC/reperfusion) and homogenized. Each sample was divided into 2 equal
      aliquots, and the SNO-RAC/Ox-RAC procedure was performed to simultaneously
      analyze SNO and oxidation. We identified 31 different SNO proteins with IPC, 27
      of which showed increased SNO compared to baseline. Of the proteins that showed
      significantly increased SNO with IPC, 76% showed decreased oxidation or no
      oxidation following ischemia and early reperfusion (IPC-IR) at the same site when
      compared to IR alone; for non-SNO proteins, oxidation was reduced by only 50%. We
      further demonstrated that IPC-induced protein SNO is quickly reversible.
      CONCLUSIONS: These results support the hypothesis that IPC-induced protein SNO
      provides cardioprotection by shielding cysteine residues from reactive oxygen
      species-induced oxidation during IR injury. Therefore, the level of protein SNO
      plays a critical role in IR injury, where ROS production is increased.

PMID- 21193740
TI  - Activation of vascular bone morphogenetic protein signaling in diabetes mellitus.
AB  - RATIONALE: Diabetes mellitus is frequently complicated by cardiovascular disease,
      such as vascular calcification and endothelial dysfunction, which have been
      associated with bone morphogenetic proteins (BMPs). OBJECTIVE: To determine
      whether hyperglycemia in vitro and diabetes in vivo promote vascular BMP activity
      and correlate with vascular calcification. METHODS AND RESULTS: Increased glucose
      augmented expression of BMP-2 and BMP-4; the BMP inhibitors matrix Gla protein
      (MGP) and Noggin; activin-like kinase receptor (ALK)1, -2, -3 and -6; the BMP
      type 2 receptor; and the vascular endothelial growth factor in human aortic
      endothelial cells (HAECs). Diabetes induced expression of the same factors in the
      aortic wall of 3 animal models of diabetes, Ins2(Akita/+) mice, db/db mice, and
      HIP rats (rats transgenic for human islet amyloid polypeptide), representative of
      types 1 and 2 diabetes. Conditioned media from glucose-treated HAECs increased
      angiogenesis in bovine aortic endothelial cells, as mediated by BMP-4, and
      osteogenesis in calcifying vascular cells, as mediated by BMP-2. BMP-4, MGP,
      ALK1, and ALK2 were predominantly expressed on the endothelial side of the aorta,
      and small interfering RNA experiments showed that these genes were regulated as a
      group. Diabetic mice and rats showed a dramatic increase in aortic BMP activity,
      as demonstrated by SMAD1/5/8 phosphorylation. This was associated with increased
      osteogenesis and calcium accumulation. These changes were prevented in the
      Ins2(Akita/+) mice by breeding them with MGP transgenic mice, which increased
      aortic BMP inhibition. CONCLUSIONS: Hyperglycemia and diabetes activate vascular
      BMP activity, which is instrumental in promoting vascular calcification and may
      be limited by increasing BMP inhibition.

PMID- 21193741
TI  - A novel mechanism of gamma/delta T-lymphocyte and endothelial activation by shear
      stress: the role of ecto-ATP synthase beta chain.
AB  - RATIONALE: Endothelial cells (ECs) have distinct mechanotransduction mechanisms
      responding to laminar versus disturbed flow patterns. Endothelial dysfunction,
      affected by imposed flow, is one of the earliest events leading to atherogenesis.
      The involvement of gamma/delta T lymphocytes in endothelial dysfunction under
      flow is largely unknown. OBJECTIVE: To investigate whether shear stress regulates
      membrane translocation of ATP synthase beta chain (ATPSbeta) in ECs, leading to
      the increased gamma/delta T-lymphocyte adhesion and the related functions. METHOD
      AND RESULTS: We applied different flow patterns to cultured ECs. Laminar flow
      decreased the level of membrane-bound ATPSbeta (ecto-ATPSbeta) and depleted
      membrane cholesterol, whereas oscillatory flow increased the level of ecto
      ATPSbeta and membrane cholesterol. Incubating ECs with cholesterol or depleting
      cellular cholesterol with beta-cyclodextrin mimicked the effect of oscillatory or
      laminar flow, respectively. Knockdown caveolin-1 by small interfering RNA
      prevented ATPSbeta translocation in response to laminar flow. Importantly,
      oscillatory flow or cholesterol treatment elevated the number of gamma/delta T
      cells binding to ECs, which was blocked by anti-ATPSbeta antibody. Furthermore,
      the incubation of gamma/delta T cells with ECs increased tumor necrosis fact
      alpha and interferon-gamma secretion from T cells and vascular cell adhesion
      molecule-1 expression in ECs. In vivo, gamma/delta T-cell adhesion and ATPSbeta
      membrane translocation was elevated in the aortic inner curvature and disturbed
      flow areas in partially ligated carotid arteries of ApoE(-/-) mice fed a high-fat
      diet. CONCLUSIONS: This study provides evidence that disturbed flow and
      hypercholesterolemia synergistically promote gamma/delta T-lymphocyte activation
      by the membrane translocation of ATPSbeta in ECs and in vivo in mice, which is a
      novel mechanism of endothelial activation.

PMID- 21193742
TI  - Preservation of tropomyosin-related kinase B (TrkB) signaling by sodium
      orthovanadate attenuates early brain injury after subarachnoid hemorrhage in
      rats.
AB  - BACKGROUND AND PURPOSE: Recent studies reported that apoptosis was involved in
      the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH). The
      aim of this study was to examine whether sodium orthovanadate (SOV) prevents post
      SAH apoptosis by modulating growth factors and its downstream receptor tyrosine
      kinases. Method- Rats were operated on with the endovascular perforation model.
      SAH animals were treated with vehicle, 3 mg/kg and 10 mg/kg SOV, and evaluated
      regarding neurofunction and brain edema. The expression of growth factors such as
      mature brain-derived neurotrophic factor, insulin-like growth factor-1, and
      vascular endothelial growth factor and phosphorylation of tropomyosin-related
      kinase B, which is a receptor tyrosine kinase for brain-derived neurotrophic
      factor and the downstream pathway in antiapoptosis, was examined by Western blot
      analysis. Neuronal cell death was measured with terminal deoxynucleotidyl
      transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling staining.
      We also administered K252a, a tropomyosin-related kinase B antagonist, to examine
      the mechanisms for neuroprotective effects by SOV. RESULTS: SOV significantly
      improved neurofunction and reduced brain edema after SAH. SOV increased mature
      brain-derived neurotrophic factor and prevented post-SAH tropomyosin-related
      kinase B inactivation and caspase-3 activation, resulting in attenuation of
      neuronal cell death in the cortex and hippocampal CA1 region. Preinjection of
      K252a abolished the beneficial effects of SOV. CONCLUSIONS: The current study
      showed that brain-derived neurotrophic factor-induced tropomyosin-related kinase
      B activation by SOV was necessary for protection against early brain injury after
      SAH.

PMID- 21193744
TI  - Regarding article "Treating arteries instead of risk factors: a paradigm change
      in management of atherosclerosis".

PMID- 21193743
TI  - White matter damage and the effect of matrix metalloproteinases in type 2
      diabetic mice after stroke.
AB  - BACKGROUND AND PURPOSE: Diabetes mellitus leads to a higher risk of ischemic
      stroke and worse outcome compared to the general population. However, there have
      been few studies on white matter (WM) damage after stroke in diabetes mellitus.
      We therefore investigated WM damage after stroke in mice with diabetes mellitus.
      METHODS: BKS.Cg-m(+/+)Lepr(db)/J (db/db) type 2 diabetes mellitus mice and db(+)
      non-diabetes mellitus mice were subjected to middle cerebral artery occlusion.
      Functional outcome, immunostaining, zymography, Western blot, and polymerase
      chain reaction were used. RESULTS: After stroke, mice with diabetes mellitus
      exhibited significantly increased lesion volume and brain hemorrhagic and
      neurological deficits compared to mice without diabetes mellitus. Bielshowsky
      silver, luxol fast blue, amyloid precursor protein, and NG2 expression were
      significantly decreased, indicating WM damage, and matrix metalloproteinase (MMP)
      9 activity was significantly increased in the ischemic brain of mice with
      diabetes mellitus. Subanalysis of similar lesions in mice with and without
      diabetes mellitus demonstrated mice with diabetes mellitus had significantly
      increased WM damage than in mice without diabetes mellitus (P<0.05). To
      investigate the mechanism underlying diabetes mellitus-induced WM damage, oxygen
      glucose deprivation-stressed premature oligodendrocyte and primary cortical
      neuron cultures were used. High glucose increased MMP-2, MMP-9, cleaved caspase-3
      levels, and apoptosis, as well as decreased cell survival and dendrite outgrowth
      in cultured primary cortical neuron. High glucose increased MMP-9, cleaved
      caspase-3 level, and apoptosis, and decreased cell proliferation and cell
      survival in cultured oligodendrocytes. Inhibition of MMP by GM6001 treatment
      significantly decreased high glucose-induced cell death and apoptosis in cultured
      primary cortical neuron and oligodendrocytes but did not alter dendrite outgrowth
      in primary cortical neuron. CONCLUSIONS: Mice with diabetes mellitus have
      increased brain hemorrhage and show more severely injured WM than mice without
      diabetes mellitus after stroke. MMP-9 upregulated in mice with diabetes mellitus
      may exacerbate WM damage after stroke in mice with diabetes mellitus.

PMID- 21193745
TI  - Soluble glycoprotein VI is raised in the plasma of patients with acute ischemic
      stroke.
AB  - BACKGROUND AND PURPOSE: Ischemic stroke induced by thrombosis may be triggered by
      atherosclerotic plaque rupture and collagen-induced platelet activation. Collagen
      induces glycoprotein VI shedding. METHODS: We measured plasma-soluble
      glycoprotein VI (sGPVI) by enzyme-linked immunosorbent assay in 159 patients with
      acute (<7-day) ischemic stroke and age/sex-matched community-based control
      subjects. RESULTS: sGPVI was elevated in stroke compared with controls
      (P=0.0168). ORs were higher in Quartile 4 for stroke cases (P=0.0121), and sGPVI
      was significantly elevated in stroke associated with large artery disease across
      Quartiles 2 to 4 and small artery disease in Quartile 4. sGPVI decreased 3 to 6
      months after antiplatelet treatment, consistent with elevated sGPVI due to
      platelet activation during the thrombotic event. sGPVI correlated with P-selectin
      (P=0.0007) and was higher in individuals with the GPVIa haplotype (P=0.024).
      CONCLUSIONS: Glycoprotein VI shedding is implicated in the pathology of acute
      ischemic stroke.

PMID- 21193746
TI  - Regarding article "Receptor activity-modifying protein-1 augments cerebrovascular
      responses to calcitonin gene-related peptide and inhibits angiotensin II-induced
      vascular dysfunction".

PMID- 21193747
TI  - Characteristics of childhood arterial ischemic stroke with normal MR angiography.
AB  - BACKGROUND AND PURPOSE: The purposes of this study were to describe clinical and
      radiological characteristics of children with arterial ischemic stroke and normal
      MRA to compare them with children with arterial ischemic stroke and abnormal MRA.
      METHODS: We conducted a retrospective review of clinical records and imaging.
      RESULTS: Forty children with arterial ischemic stroke and normal MRA were
      identified (24 male; median age, 55 months). MRA had been acquired <24 hours of
      symptom onset in 4, at 24 to 48 hours in 10, 48 to 96 hours in 10, 4 to 7 days in
      10, and >1 week in 6 children (median, 4 days). Ten of 40 had prior diagnoses (5
      cardiac, 5 malignancies). Other risk factors were identified in 30 (1 in 17 and
      >1 in 13; prothrombotic abnormalities in 14, prior Varicella in 7, anemia in 7,
      minor trauma in 4). Infarction was confined to the lenticulostriate branches of
      the middle cerebral artery in 21 of 40. Two patients had further clinical events,
      both with new infarcts; 28 patients were reimaged and MRA remained normal in all.
      Although similar in terms of age and gender to those with abnormal MRA, children
      with normal MRA were significantly more likely to have at least 1 RF (P=0.012).
      Those with abnormal MRA were significantly more likely to have multiple territory
      infarcts (P<0.001), but lesion topography was otherwise not predictive of
      abnormal MRA (P=0.45). Abnormal MRA was significantly associated with clinical
      recurrence (P<0.001). CONCLUSIONS: Children with arterial ischemic stroke and
      normal MRA are not a distinct demographic group but are more likely to have
      single-territory lesions and have nonvascular risk factors. The stroke mechanism
      in children with normal MRA remains unclear.

PMID- 21193748
TI  - Transient ischemic attack and acute ischemic stroke: associations with retinal
      microvascular signs.
AB  - BACKGROUND AND PURPOSE: Small vessel disease plays a role in cerebral events. We
      aimed to investigate the prevalence and patterns of retinal microvascular signs
      (surrogates for cerebral small vessel disease) among patients with transient
      ischemic attack (TIA) or acute stroke and population control subjects. METHODS:
      Patients with TIA or acute stroke aged >=49 years admitted to hospitals in
      Melbourne and Sydney, Australia, were recruited to the Multi-Centre Retina and
      Stroke Study (n=693, 2005 to 2007). Control subjects were Blue Mountains Eye
      Study participants aged >=49 years without TIAs or stroke (n=3384, 1992 to 1994,
      west of Sydney). TIA, ischemic stroke, or primary intracerebral hemorrhage was
      classified using standardized neurological assessments, including neuroimaging.
      Retinal microvascular signs (retinopathy, focal arteriolar narrowing,
      arteriovenous nicking, enhanced arteriolar light reflex) were assessed from
      retinal photographs masked to clinical information. RESULTS: Patients with TIA or
      acute stroke were older than control subjects and more likely to have stroke risk
      factors. After adjustment for study site and known risk factors, all retinal
      microvascular signs were more common in patients with TIA or acute stroke than in
      control subjects (OR, 1.9 to 8.7; P<0.001). Patients with TIA and those with
      ischemic stroke had similar prevalences of nondiabetic retinopathy (26.9% versus
      29.5%; OR, 0.8; 95% CI, 0.5 to 1.6), diabetic retinopathy (55.5% versus 50.0%;
      OR, 1.3; 95% CI, 0.4 to 3.6), focal arteriolar narrowing (15.6% versus 18.4%; OR,
      0.8; 95% CI, 0.4 to 1.5), and arteriovenous nicking (23.0% versus 17.8%; OR, 1.4;
      95% CI, 0.7 to 2.7). CONCLUSIONS: Patients with TIA and acute stroke may share
      similar risk factors or pathogenic mechanisms.

PMID- 21193749
TI  - Pharmacologically augmented S-nitrosylated hemoglobin improves recovery from
      murine subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: S-nitrosylated hemoglobin (S-nitrosohemoglobin) has been
      implicated in the delivery of O(2) to tissues through the regulation of
      microvascular blood flow. This study tested the hypothesis that enhancement of S
      nitrosylated hemoglobin by ethyl nitrite inhalation improves outcome after
      experimental subarachnoid hemorrhage (SAH). METHODS: A preliminary dosing study
      identified 20 ppm ethyl nitrite as a concentration that produced a 4-fold
      increase in S-nitrosylated hemoglobin concentration with no increase in
      methemoglobin. Mice were subjected to endovascular perforation of the right
      anterior cerebral artery and were treated with 20 ppm ethyl nitrite in air, or
      air alone for 72 hours, after which neurologic function, cerebral vessel
      diameter, brain water content, cortical tissue Po(2), and parenchymal red blood
      cell flow velocity were measured. RESULTS: At 72 hours after hemorrhage, air- and
      ethyl nitrite-exposed mice had similarly sized blood clots. Ethyl nitrite
      improved neurologic score and rotarod performance; abated SAH-induced
      constrictions in the ipsilateral anterior, middle cerebral, and internal carotid
      arteries; and prevented an increase in ipsilateral brain water content. Ethyl
      nitrite inhalation increased red blood cell flow velocity and cortical tissue
      Po(2) in the ipsilateral cortex with no effect on systemic blood pressure.
      CONCLUSIONS: Targeted S-nitrosylation of hemoglobin improved outcome parameters,
      including vessel diameter, tissue blood flow, cortical tissue Po(2), and
      neurologic function in a murine SAH model. Augmenting endogenous Po(2)-dependent
      delivery of NO bioactivity to selectively dilate the compromised cerebral
      vasculature has significant clinical potential in the treatment of SAH.

PMID- 21193750
TI  - Autoantibodies against the fibrinolytic receptor, annexin A2, in cerebral venous
      thrombosis.
AB  - BACKGROUND AND PURPOSE: Cerebral venous thrombosis (CVT) may be a manifestation
      of underlying autoimmune disease. Antibodies against annexin A2 (anti-A2Ab)
      coincide with antiphospholipid syndrome, in which antiphospholipid antibodies
      (aPLA) are associated with thrombosis in any vascular bed. Annexin A2, a
      profibrinolytic receptor and binding site for beta2-glycoprotein-I, the main
      target for aPLA, is highly expressed on cerebral endothelium. Here we evaluate
      the prevalence of anti-A2Ab in CVT. METHODS: Forty individuals with objectively
      documented CVT (33 women and 7 men) and 145 healthy controls were prospectively
      studied for hereditary and acquired prothrombotic risk factors, classical aPLA,
      and anti-A2Ab. RESULTS: One or more prothrombotic risk factors were found in 85%
      of CVT subjects, (pregnancy/puerperium in 57.5%, classical aPLA in 22.5%, and
      hereditary procoagulant risk factors in 17.5%). Anti-A2Ab (titer >3 SD) were
      significantly more prevalent in patients with CVT (12.5%) than in healthy
      individuals (2.1%, P<0.01, OR, 5.9). CONCLUSIONS: Anti-A2Ab are significantly
      associated with CVT and may define a subset of individuals with immune-mediated
      cerebral thrombosis.

PMID- 21193751
TI  - Diffusion tensor imaging and gait in elderly persons with cerebral small vessel
      disease.
AB  - BACKGROUND AND PURPOSE: Although cerebral small vessel disease, including white
      matter lesions (WML) and lacunar infarcts, is associated with gait disturbances,
      not all individuals with small vessel disease have these disturbances. Identical
      appearing WML on MRI could reflect different degrees of microstructural
      integrity. Moreover, conventional MRI does not assess the integrity of normal
      appearing white matter (NAWM). We therefore investigated the relation between
      white matter integrity assessed by diffusion tensor imaging in WML, NAWM, several
      regions of interest, and gait. METHODS: A total of 484 nondemented elderly
      persons between 50 and 85 years old with cerebral small vessel disease were
      included in this analysis and underwent MRI and diffusion tensor imaging
      scanning. Mean diffusivity and fractional anisotropy within WML, NAWM, and
      regions of interest were related to quantitative and semiquantitative gait
      parameters. RESULTS: Mean diffusivity in the WML was inversely related with gait
      (velocity beta=-0.15; P=0.002). For the fractional anisotropy, this relation was
      less evident. The same was found in the NAWM (velocity beta=-0.21; P<0.001) and
      for some parameters also after additional adjustment for WML and lacunar
      infarcts. CONCLUSIONS: This study indicates that integrity of both WML and NAWM,
      beyond the detection limit of conventional MRI, is associated with gait
      disturbances.

PMID- 21193752
TI  - Wide variation in definition, detection, and description of lacunar lesions on
      imaging.
AB  - BACKGROUND AND PURPOSE: Variation in the definition of lacunar lesions on imaging
      and difficulties in their detection may be hampering lacunar stroke research. We
      assessed literature definitions of imaging lacunar lesions and the definitions
      and detection of lacunar lesions among small-vessel disease researchers. METHODS:
      We assessed definitions of imaging lacunar lesion in 50 randomly selected
      articles from 3 stroke-related journals and an online survey of small-vessel
      disease researchers. In the literature review, we assessed clinical/imaging
      definitions of lacunar stroke. In the survey, we assessed lacunar lesion
      detection, effects of lesion appearance, background white matter lesions, and
      provision of relevant data. RESULTS: Among 50 articles, imaging definitions were
      varied and often limited; size was stated in 21 of 43 (49%) studies of acute and
      in 9 of 20 (45%) studies of old lesions and site in 18 (42%) and 4 (20%),
      respectively. Clinical definitions also varied, and images were read mostly by
      nonradiologists. Among 56 survey respondents, multiple descriptions were used for
      recent and old, symptomatic and asymptomatic, lesions on imaging. Most agreed on
      definitions for site (98%) and "old lacunar infarct" (61%) size. Cavitated (vs
      noncavitated) lesions were usually identified as lacunar lesions; with increasing
      white matter lesions, however, noncavitated lesions were very unlikely to be
      identified, even with prior imaging available (7.8%). CONCLUSIONS: Imaging
      definitions of lacunar lesions vary widely, in part due to variation in lesion
      detection and classification. A consensus for imaging definitions of small-vessel
      disease features would be helpful.

PMID- 21193753
TI  - Regarding article "Guidelines for the management of spontaneous intracerebral
      hemorrhage: a guideline for healthcare professionals from the American Heart
      Association/American Stroke Association".

PMID- 21193754
TI  - Evidence or science based? There is a time for every purpose.

PMID- 21193755
TI  - Dental sealants.

PMID- 21193756
TI  - Dentin hypersensitivity.

PMID- 21193757
TI  - Career options.

PMID- 21193758
TI  - Orthodontic brackets.

PMID- 21193759
TI  - Public options.

PMID- 21193760
TI  - Coverage denied.

PMID- 21193761
TI  - Dental radiographs.

PMID- 21193762
TI  - Reading habits.

PMID- 21193763
TI  - Recalling pain.

PMID- 21193764
TI  - Development of a clinical guideline to predict undiagnosed diabetes in dental
      patients.
AB  - BACKGROUND: In 2007, 17.9 million people in the United States had diagnosed
      diabetes, and 5.7 million had undiagnosed diabetes. The authors developed a
      clinical guideline to help dentists identify patients with undiagnosed diabetes.
      METHODS: The authors used classification and regression tree (CART) methods to
      generate different prediction models using data from the Third National Health
      and Nutrition Examination Survey (NHANES III) (1988-1994) and data from NHANES
      2003-2004 for external validation. They classified participants who answered "No"
      to the question "Have you ever been told by a physician that you have diabetes?"
      and who had a fasting plasma glucose level greater than or equal to 126
      milligrams per deciliter as having undiagnosed diabetes. The authors used oral
      examination data regarding the presence or absence of periodontitis and waist
      circumference, as well as data on participants' self-reported oral health status,
      weight, age, family history and race or ethnicity. The authors chose the best
      prediction model by means of 10-fold cross-validation, as well as internal and
      external validation methods, which evaluated each prediction model by comparing
      sensitivity, specificity, area under the receiver operating characteristic curve
      and ease of use criteria (N = 7,545). RESULTS: The authors' final clinical
      guideline for predicting undiagnosed diabetes in dental patients had a
      sensitivity of 82.4 percent, a specificity of 52.8 percent and a receiver
      operating characteristic area under the curve of 0.72. They found that waist
      circumference, age, self-reported oral health status, self-reported race or
      ethnicity and self-reported weight information could be used to predict the risk
      of having undiagnosed diabetes (range, 0.1 to 9.1 percent). CONCLUSION: Dental
      care providers should consider using a clinical guideline that includes the
      following predictors: waist circumference, age, self-reported oral health, self
      reported weight and self-reported race or ethnicity, as well as any additional
      information on periodontal status and family history of diabetes. CLINICAL
      IMPLICATIONS: This clinical guideline could help dentists identify patients with
      undiagnosed diabetes, resulting in the early identification of dental patients
      who require treatment for diabetes and, thus, reduce morbidity and health care
      costs.

PMID- 21193765
TI  - The therapeutic applications of and risks associated with acetaminophen use: a
      review and update.
AB  - BACKGROUND: In response to the April 2010 U.S. Food and Drug Administration's
      (FDA's) revision of warning labeling for over-the-counter (OTC) acetaminophen, or
      N-acetyl-p-aminophenol (APAP), products, the authors reviewed APAP's potential
      for liver toxicity. TYPES OF STUDIES REVIEWED: The authors reviewed the
      literature in which investigators examined data related to the epidemiology of
      APAP-related liver toxicity, studies in which the investigators evaluated the
      risk factors for its occurrence and case reports. They included articles that
      were used by the FDA as the basis for establishing the new labeling requirements.
      RESULTS: Findings from the literature in which investigators have examined the
      relationship between APAP and liver toxicity indicate several key risk factors.
      Foremost are the extensive use of one or more APAP-containing compounds
      (particularly combinations with opioid agents) and the small margin of safety
      between the therapeutic and toxic doses. Both of these factors lead to
      unintentional or intentional drug overdose. Concurrent use of alcohol may
      contribute to hepatotoxicity, but it may be related to behavior rather than
      biochemical mechanisms involved in liver damage. CONCLUSIONS: The widespread use
      of APAP has contributed to a substantial increase in the number of cases of acute
      liver toxicity in the United States. Since APAP is a component of many
      prescription and OTC medications, unintentional overdose can occur. CLINICAL
      IMPLICATIONS: APAP has numerous applications in dentistry, but if it is used
      conjointly for other conditions, the risk of the patient's experiencing an
      overdose increases. In the context of recent FDA concerns about the increased
      incidence of APAP-related liver toxicity, the authors provide recommendations for
      safe prescribing practices for APAP. Practitioners should caution patients to
      follow recommended dosage instructions and avoid taking multiple APAP-containing
      products.

PMID- 21193766
TI  - Medical emergencies in a dental office: inhalation and ingestion of orthodontic
      objects.
AB  - BACKGROUND: The authors reviewed the literature regarding inhalation and
      ingestion of orthodontic appliances and suggest ways to manage and prevent these
      events. TYPES OF STUDIES REVIEWED: The authors conducted literature searches of
      free text and Medical Subject Headings terms by using PubMed and Embase databases
      and selected appropriate studies. They analyzed retrieved articles according to
      several parameters: inhalation or ingestion event, number of cases, patient's sex
      and age, type of orthodontic appliance, in-office event or out-of-office event,
      and medical treatment. RESULTS: The authors found a total of 2,279 articles in
      their preliminary search. Eighteen reports of 24 cases from this search met all
      of the search criteria (that is, clinical studies, case reports or reviews
      limited to English, Hebrew or Arabic on any form of aspiration or inhalation of
      orthodontic appliances). Most cases (67 percent) involved ingested objects, and
      of those cases, the majority (57 percent) occurred in female patients. Most cases
      (85 percent) occurred outside the orthodontist's office. Seventeen patients (71
      percent) had been treated with a fixed orthodontic appliance. In 60 percent of
      cases, the maxilla was involved. With one exception, no severe complications were
      reported (only seven patients were examined in a hospital emergency department),
      and patients were discharged uneventfully from the orthodontic office or
      emergency department. CLINICAL IMPLICATIONS: Orthodontists and team members
      should participate in medical emergency management courses that emphasize the use
      of guidelines in cases of inhalation or ingestion of orthodontic objects. Each
      orthodontist's office should develop written emergency protocols for out-of
      office events and present them to patients and their parents at the start of
      treatment.

PMID- 21193767
TI  - Multifocal pigmentation of the oral cavity. Oral melanoacanthoma.

PMID- 21193768
TI  - Dental care and associated factors among older adults with schizophrenia.
AB  - BACKGROUND: Few data are available concerning dental care in older adults with
      schizophrenia. The authors examined the utilization of dental care and factors
      related to dental treatment in this population. METHODS: The sample consisted of
      198 community-dwelling participants 55 years and older with schizophrenia and a
      community comparison group of 113 participants. The authors adapted a model of
      illness behavior in later life as the basis for selection of 18 predictor
      variables of annual dental care visits. RESULTS: The study results showed no
      significant differences between the schizophrenia and community comparison groups
      with regard to the percentage of participants (28 and 31 percent, respectively)
      reporting having had at least two dental visits in the previous year or one
      dental visit (48 and 54 percent, respectively). However, the results showed
      significant differences in the percentage of participants in the schizophrenia
      and community comparison groups who stated that they experienced problems with
      their teeth or dentures (41 and 23 percent, respectively). When examining
      participants in the schizophrenia group separately, the authors found four
      variables that were significantly associated with having had at least one dental
      visit: financial well-being (odds ratio [OR] = 1.12), better executive cognitive
      functioning (OR = 1.11), fewer perceived problems with teeth or dentures (OR =
      0.33) and fewer oral dyskinesias (OR = 0.86). CONCLUSIONS: Most older adults with
      schizophrenia in this study did not receive at least two dental visits per year,
      although their frequency of care was no worse than that of their age-matched
      peers. Psychiatric assessments should include questions about dental care. The
      greatest improvement in dental care for such patients likely is to occur by
      targeting people who report having more problems with their teeth, including oral
      dyskinesias; those who have greater cognitive impairments, especially in
      executive functioning; and those who have diminished financial resources.

PMID- 21193769
TI  - Apical root resorption is associated with comprehensive orthodontic treatment but
      not clearly dependent on prior tooth characteristics or orthodontic techniques.
AB  - SYSTEMATIC REVIEW CONCLUSION: Increased incidence and severity of external apical
      root resorption (EARR) occurred in patients undergoing comprehensive orthodontic
      therapy, especially when therapy involved higher levels of force than those
      commonly used for orthodontic tooth movement. CRITICAL SUMMARY ASSESSMENT:
      Results from a high-quality systematic review of 11 randomized clinical trials
      (RCTs) suggests that EARR has a multifactorial etiology; is associated with
      comprehensive orthodontics; supports the clinical use of light forces, especially
      during intrusion of teeth; and requires higher-quality research. EVIDENCE QUALITY
      RATING: Limited.

PMID- 21193770
TI  - Exploring socioeconomic disparities in self-reported oral health among
      adolescents in california.
AB  - BACKGROUND: Socioeconomic factors are associated with disparities in oral health
      among adolescents; however, the underlying reasons are not clear. The authors
      conducted a study to determine if known indicators of oral health can explain
      such disparities. METHODS: The authors examined data from a 2007 California
      Health Interview Survey of adolescents. The outcome of interest was self-reported
      condition of the teeth; covariates were socioeconomic status (SES) (that is,
      family poverty level and parental education) and a range of other variables
      representing health-influencing behaviors, dental care and other social factors.
      The authors conducted analyses by using logistic regression to explain
      disparities in self-reported condition of the teeth associated with SES. RESULTS:
      The authors found that socioeconomic disparities decreased substantially after
      they added all potential explanatory variables to the model, leaving poverty
      level as the only variable associated with differences in the self-reported
      condition of the teeth. Adolescents living below the federal poverty guidelines
      were more likely to report that the condition of their teeth was fair or poor
      than were adolescents who were least poor (odds ratio = 1.58; 95 percent
      confidence interval, 1.04-2.41). In multivariate analyses, further oral health
      disparities existed in relation to behaviors that influence health, social
      environment and dental care. CONCLUSIONS: The results of this study showed that a
      number of factors decreased, but did not eliminate, the observed relationship
      between SES and oral health in Californian adolescents. Most of these explanatory
      factors are modifiable, indicating that socioeconomic differences associated with
      oral health among adolescents may be amenable to change. Practice Implications.
      By promoting a healthy lifestyle (including healthy diet, exercise and regular
      dental attendance) and conveying to patients in languages other than English how
      to maintain oral health, dentists may be able to ameliorate the effects of
      socioeconomic disparities in oral health.

PMID- 21193771
TI  - Poor performance and termination.

PMID- 21193772
TI  - Are there ethical considerations to keep in mind as a dentist approaches
      retirement?

PMID- 21193773
TI  - For the Dental Patient...What is gum disease?

PMID- 21193776
TI  - Gender differences in inflammatory processes could explain poorer prognosis for
      males.

PMID- 21193777
TI  - Lame from birth: early concepts of cerebral palsy.
AB  - Deformations have been attributed to supernatural causes since antiquity.
      Cerebral palsy was associated with God's wrath, witchcraft, the evil eye, or
      maternal imagination. Greek scholars recommended prevention by tight swaddling, a
      custom that persisted into modern times. In the Middle Ages, the midwife's
      negligence was held responsible as was difficult teething. Morgagni described in
      1769 that the neonatal brain can liquefy, and Bednar described leukomalacia in
      1850 as a distinct disorder of the newborn. In 1861, Little associated cerebral
      palsies with difficult or protracted labor and neonatal asphyxia, but he was
      challenged by Freud, who in 1897 declared that most cases are prenatal in origin.
      In 1868, Virchow demonstrated inflammatory changes, a view recently confirmed by
      Leviton and Nelson. Although a causal relationship of cerebral palsy to the birth
      never has been established, the habit to put the blame for cerebral palsy on
      someone remained a frequent attitude.

PMID- 21193778
TI  - Learning about what others were doing: verb aspect and attributions of mundane
      and criminal intent for past actions.
AB  - Scientists have long been interested in understanding how language shapes the way
      people relate to others, yet it remains unclear how formal aspects of language
      influence person perception. We tested whether the attribution of intentionality
      to a person is influenced by whether the person's behaviors are described as what
      the person was doing or as what the person did (imperfective vs. perfective
      aspect). In three experiments, participants who read what a person was doing
      showed enhanced accessibility of intention-related concepts and attributed more
      intentionality to the person, compared with participants who read what the person
      did. This effect of the imperfective aspect was mediated by a more detailed set
      of imagined actions from which to infer the person's intentions and was found for
      both mundane and criminal behaviors. Understanding the possible intentions of
      others is fundamental to social interaction, and our findings show that verb
      aspect can profoundly influence this process.

PMID- 21193779
TI  - The reminiscence bump reconsidered: children's prospective life stories show a
      bump in young adulthood.
AB  - The reminiscence bump-the reporting of more memories from young adulthood than
      from other stages of life-is considered a hallmark of autobiographical memory
      research. The most prevalent explanations for this effect assume that events in
      young adulthood are favored because of the way they are encoded and maintained in
      long-term memory. Here we show that a similar increase of events in early
      adulthood is found when children narrate their personal futures. In Study 1,
      children wrote their future life stories. The events in these life stories were
      mostly life-script events, and their distribution showed a clear bump in young
      adulthood. In Study 2, children were prompted by word cues to write down events
      from their future lives. The events generated consisted mostly of non-life-script
      events, and those events did not show a bump in young adulthood. Our findings
      challenge prevailing explanations of the reminiscence bump and suggest that the
      cultural life script forms an overarching organizational principle for
      autobiographical memories and future representations across the life span.

PMID- 21193780
TI  - Direct electrophysiological measurement of attentional templates in visual
      working memory.

PMID- 21193781
TI  - Let It Be: microRNAs impact interstitial lung disease.

PMID- 21193782
TI  - Intention to test is intention to treat.

PMID- 21193783
TI  - What does multi-pollutant air pollution research mean?

PMID- 21193784
TI  - Better supportive care, less ARDS: just do it?

PMID- 21193785
TI  - An official American Thoracic Society statement: Treatment of fungal infections
      in adult pulmonary and critical care patients.
AB  - With increasing numbers of immune-compromised patients with malignancy,
      hematologic disease, and HIV, as well as those receiving immunosupressive drug
      regimens for the management of organ transplantation or autoimmune inflammatory
      conditions, the incidence of fungal infections has dramatically increased over
      recent years. Definitive diagnosis of pulmonary fungal infections has also been
      substantially assisted by the development of newer diagnostic methods and
      techniques, including the use of antigen detection, polymerase chain reaction,
      serologies, computed tomography and positron emission tomography scans,
      bronchoscopy, mediastinoscopy, and video-assisted thorascopic biopsy. At the same
      time, the introduction of new treatment modalities has significantly broadened
      options available to physicians who treat these conditions. While traditionally
      antifungal therapy was limited to the use of amphotericin B, flucytosine, and a
      handful of clinically available azole agents, current pharmacologic treatment
      options include potent new azole compounds with extended antifungal activity,
      lipid forms of amphotericin B, and newer antifungal drugs, including the
      echinocandins. In view of the changing treatment of pulmonary fungal infections,
      the American Thoracic Society convened a working group of experts in fungal
      infections to develop a concise clinical statement of current therapeutic options
      for those fungal infections of particular relevance to pulmonary and critical
      care practice. This document focuses on three primary areas of concern: the
      endemic mycoses, including histoplasmosis, sporotrichosis, blastomycosis, and
      coccidioidomycosis; fungal infections of special concern for immune-compromised
      and critically ill patients, including cryptococcosis, aspergillosis,
      candidiasis, and Pneumocystis pneumonia; and rare and emerging fungal infections.

PMID- 21193786
TI  - Recommended reading from the University of Michigan Pulmonary and Critical Care
      Fellows: Marc Peters-Golden, M.D., program director.

PMID- 21193787
TI  - Golden s sign.

PMID- 21193788
TI  - Outcome reporting in asthma research.

PMID- 21193789
TI  - Totally implantable vascular access devices in adult patients for cystic fibrosis
      management.

PMID- 21193790
TI  - Ceramide and cystic fibrosis lung disease.

PMID- 21193792
TI  - EBUS-TBNA performs well in the diagnosis of isolated thoracic tuberculous
      lymphadenopathy.

PMID- 21193791
TI  - Pulmonary coccidioidomycosis with peritoneal involvement mimicking lung cancer
      with peritoneal carcinomatosis.

PMID- 21193793
TI  - Coexistence of allergic bronchopulmonary aspergillosis and active pulmonary
      tuberculosis.

PMID- 21193794
TI  - Prednisolone ameliorates idiopathic pulmonary arterial hypertension.

PMID- 21193795
TI  - Is the reference arterial ph higher than usually acknowledged?

PMID- 21193796
TI  - An unusual localized progressive fibrotic cavity mimicking lung malignancy in
      idiopathic pulmonary fibrosis.

PMID- 21193797
TI  - Late endobronchial metastasis from rectal cancer that mimics a primary lung
      cancer.

PMID- 21193799
TI  - Getting published: responding to the "printing press".

PMID- 21193798
TI  - RecA K72R filament formation defects reveal an oligomeric RecA species involved
      in filament extension.
AB  - Using an ensemble approach, we demonstrate that an oligomeric RecA species is
      required for the extension phase of RecA filament formation. The RecA K72R mutant
      protein can bind but not hydrolyze ATP or dATP. When mixed with other RecA
      variants, RecA K72R causes a drop in the rate of ATP hydrolysis and has been used
      to study disassembly of hydrolysis-proficient RecA protein filaments. RecA K72R
      filaments do not form in the presence of ATP but do so when dATP is provided. We
      demonstrate that in the presence of ATP, RecA K72R is defective for extension of
      RecA filaments on DNA. This defect is partially rescued when the mutant protein
      is mixed with sufficient levels of wild type RecA protein. Functional extension
      complexes form most readily when wild type RecA is in excess of RecA K72R. Thus,
      RecA K72R inhibits hydrolysis-proficient RecA proteins by interacting with them
      in solution and preventing the extension phase of filament assembly.

PMID- 21193800
TI  - Thoughts on being productive during a graduate program: the process and benefits
      of a peer working group.

PMID- 21193801
TI  - Feasibility of voluntary menu labeling among locally owned restaurants.
AB  - In 2007, Tacoma-Pierce County Health Department launched a restaurant menu
      labeling project called SmartMenu. The objective was to recruit locally owned
      restaurants to voluntarily post basic nutrition information on their menus or
      menu boards. Participating restaurants submitted recipes to an independent
      contractor for nutritional analysis and agreed to post calorie, fat,
      carbohydrate, and sodium values on new menus within 90 days of receiving results.
      Vigorous recruitment efforts by the Health Department between June 2007 and
      September 2008 included free advertising, consultation with a Registered
      Dietitian, and free nutritional analysis. By the end of 2008, a total of 24
      restaurants participated in the program. Significant barriers to participation
      included infrequent use of standardized recipes, perceived business risk of
      labeling, and low perceived customer demand for nutrition information. Key
      program elements, recruitment strategies, and costs are discussed. Results have
      important implications for future efforts to increase the adoption of menu
      labeling by locally owned and operated restaurants.

PMID- 21193802
TI  - Contractile response of human anterior vaginal muscularis in women with and
      without pelvic organ prolapse.
AB  - The aim of this study was to compare the contractility of the anterior vaginal
      muscularis (AVM) from women with and without pelvic organ prolapse (POP). In
      vitro experiments were performed to measure the peak force generated in response
      to potassium chloride (KCl; 125 mmol/L) and phenylephrine by AVM tissue from
      women with and without POP. Cross-sectional areas and co-localization of
      alpha(1A) adrenergic receptor protein with smooth muscle alpha-actin in AVM
      strips were determined by histology and immunofluorescence, respectively. There
      were no differences in the mean amplitude of force generated in response to KCl
      normalized to either wet weight or muscle cross-sectional area (mN/mm(2)) between
      women with and without POP (P > .30). However, AVM from women with prolapse
      produced a significantly higher mean force to KCl normalized to total cross
      sectional area compared to controls (P = .007). While the control samples
      demonstrated a consistent response to phenylephrine, there was no response to
      this stimulant generated by AVM tissue from women with POP. The proportion of co
      localized alpha(1A) adrenergic receptors with smooth muscle alpha actin in AVM
      tissue was significantly less in women with POP compared to normal controls (P <
      .0001). Although there was significantly greater tissue stress generated by AVM
      from women with prolapse compared to controls, there were no differences in
      muscle stress. Absent response to phenylephrine by AVM from women with prolapse
      may be related to a lower expression of alpha(1A) adrenergic receptors in vaginal
      smooth muscle.

PMID- 21193803
TI  - Aberrant expression of apoptosis-related molecules in endometriosis: a possible
      mechanism underlying the pathogenesis of endometriosis.
AB  - Endometriosis, a disease affecting 3% to 10% of women of reproductive age, is
      characterized by the ectopic growth of endometrial tissue under the influence of
      estrogen. It is also becoming recognized as a condition in which ectopic
      endometrial cells exhibit abnormal proliferative and apoptotic regulation in
      response to appropriate stimuli. Apoptosis plays a critical role in maintaining
      tissue homeostasis and represents a normal function to eliminate excess or
      dysfunctional cells. Accumulated evidence suggests that, in healthy women,
      endometrial cells expelled during menstruation do not survive in ectopic
      locations because of programmed cell death, while decreased apoptosis may lead to
      the ectopic survival and implantation of these cells, resulting in the
      development of endometriosis. Both the inability of endometrial cells to transmit
      a "death" signal and the ability of endometrial cells to avoid cell death have
      been associated with increased expression of antiapoptotic factors and decreased
      expression of preapoptotic factors. Further investigations may elucidate the role
      of apoptosis-associated molecules in the pathogenesis of endometriosis. Medical
      treatment with apoptosis-inducing agents may be novel and promising therapeutic
      strategy for endometriosis.

PMID- 21193804
TI  - Gene expression profile of rat prostate during pubertal growth and maturation.
AB  - Temporal gene expression profiling can provide valuable insight into mechanisms
      of differentiation and may be helpful in laying a foundation for characterization
      of the molecular aspects of development. Prostate development begins in fetal
      life and is complete at sexual maturity, and androgen stimulation is both
      necessary and sufficient for development and maturity of the prostate. In this
      study, we investigated gene expression profiles of rat prostate at 3 different
      developmental stages (2 weeks, 3.5 weeks, and 8 weeks), when serum testosterone
      levels are low, intermediate, and high. Through this analysis, we attempted to
      narrow down genes whose expression is affected by androgen increase during
      pubertal growth and maturation of the prostate.

PMID- 21193805
TI  - Fingerprint reconstruction: from minutiae to phase.
AB  - Fingerprint matching systems generally use four types of representation schemes:
      grayscale image, phase image, skeleton image, and minutiae, among which minutiae
      based representation is the most widely adopted one. The compactness of minutiae
      representation has created an impression that the minutiae template does not
      contain sufficient information to allow the reconstruction of the original
      grayscale fingerprint image. This belief has now been shown to be false; several
      algorithms have been proposed that can reconstruct fingerprint images from
      minutiae templates. These techniques try to either reconstruct the skeleton
      image, which is then converted into the grayscale image, or reconstruct the
      grayscale image directly from the minutiae template. However, they have a common
      drawback: Many spurious minutiae not included in the original minutiae template
      are generated in the reconstructed image. Moreover, some of these reconstruction
      techniques can only generate a partial fingerprint. In this paper, a novel
      fingerprint reconstruction algorithm is proposed to reconstruct the phase image,
      which is then converted into the grayscale image. The proposed reconstruction
      algorithm not only gives the whole fingerprint, but the reconstructed fingerprint
      contains very few spurious minutiae. Specifically, a fingerprint image is
      represented as a phase image which consists of the continuous phase and the
      spiral phase (which corresponds to minutiae). An algorithm is proposed to
      reconstruct the continuous phase from minutiae. The proposed reconstruction
      algorithm has been evaluated with respect to the success rates of type-I attack
      (match the reconstructed fingerprint against the original fingerprint) and type
      II attack (match the reconstructed fingerprint against different impressions of
      the original fingerprint) using a commercial fingerprint recognition system.
      Given the reconstructed image from our algorithm, we show that both types of
      attacks can be successfully launched against a fingerprint recognition system.

PMID- 21193806
TI  - Hyperconnected attribute filters based on k-flat zones.
AB  - In this paper, we present a new method for attribute filtering, combining
      contrast and structural information. Using hyperconnectivity based on k-flat
      zones, we improve the ability of attribute filters to retain internal details in
      detected objects. Simultaneously, we improve the suppression of small, unwanted
      detail in the background. We extend the theory of attribute filters to
      hyperconnectivity and provide a fast algorithm to implement the new method. The
      new version is only marginally slower than the standard Max-Tree algorithm for
      connected attribute filters, and linear in the number of pixels or voxels. It is
      two orders of magnitude faster than anisotropic diffusion. The method is
      implemented in the form of a filtering rule suitable for handling both increasing
      (size) and nonincreasing (shape) attributes. We test this new framework on
      nonincreasing shape filters on both 2D images from astronomy, document
      processing, and microscopy, and 3D CT scans, and show increased robustness to
      noise while maintaining the advantages of previous methods.

PMID- 21193807
TI  - An extended grammar system for learning and recognizing complex visual events.
AB  - For a grammar-based approach to the recognition of visual events, there are two
      major limitations that prevent it from real application. One is that the event
      rules are predefined by domain experts, which means huge manual cost. The other
      is that the commonly used grammar can only handle sequential relations between
      subevents, which is inadequate to recognize more complex events involving
      parallel subevents. To solve these problems, we propose an extended grammar
      approach to modeling and recognizing complex visual events. First, motion
      trajectories as original features are transformed into a set of basic motion
      patterns of a single moving object, namely, primitives (terminals) in the grammar
      system. Then, a Minimum Description Length (MDL) based rule induction algorithm
      is performed to discover the hidden temporal structures in primitive stream,
      where Stochastic Context-Free Grammar (SCFG) is extended by Allen's temporal
      logic to model the complex temporal relations between subevents. Finally, a
      Multithread Parsing (MTP) algorithm is adopted to recognize interesting complex
      events in a given primitive stream, where a Viterbi-like error recovery strategy
      is also proposed to handle large-scale errors, e.g., insertion and deletion
      errors. Extensive experiments, including gymnastic exercises, traffic light
      events, and multi-agent interactions, have been executed to validate the
      effectiveness of the proposed approach.

PMID- 21193808
TI  - Cost-sensitive boosting.
AB  - A novel framework is proposed for the design of cost-sensitive boosting
      algorithms. The framework is based on the identification of two necessary
      conditions for optimal cost-sensitive learning that 1) expected losses must be
      minimized by optimal cost-sensitive decision rules and 2) empirical loss
      minimization must emphasize the neighborhood of the target cost-sensitive
      boundary. It is shown that these conditions enable the derivation of cost
      sensitive losses that can be minimized by gradient descent, in the functional
      space of convex combinations of weak learners, to produce novel boosting
      algorithms. The proposed framework is applied to the derivation of cost-sensitive
      extensions of AdaBoost, RealBoost, and LogitBoost. Experimental evidence, with a
      synthetic problem, standard data sets, and the computer vision problems of face
      and car detection, is presented in support of the cost-sensitive optimality of
      the new algorithms. Their performance is also compared to those of various
      previous cost-sensitive boosting proposals, as well as the popular combination of
      large-margin classifiers and probability calibration. Cost-sensitive boosting is
      shown to consistently outperform all other methods.

PMID- 21193809
TI  - Decoupled active contour (DAC) for boundary detection.
AB  - The accurate detection of object boundaries via active contours is an ongoing
      research topic in computer vision. Most active contours converge toward some
      desired contour by minimizing a sum of internal (prior) and external (image
      measurement) energy terms. Such an approach is elegant, but suffers from a slow
      convergence rate and frequently misconverges in the presence of noise or complex
      contours. To address these limitations, a decoupled active contour (DAC) is
      developed which applies the two energy terms separately. Essentially, the DAC
      consists of a measurement update step, employing a Hidden Markov Model (HMM) and
      Viterbi search, and then a separate prior step, which modifies the updated curve
      based on the relative strengths of the measurement uncertainty and the
      nonstationary prior. By separating the measurement and prior steps, the algorithm
      is less likely to misconverge; furthermore, the use of a Viterbi optimizer allows
      the method to converge far more rapidly than energy-based iterative solvers. The
      results clearly demonstrate that the proposed approach is robust to noise, can
      capture regions of very high curvature, and exhibits limited dependence on
      contour initialization or parameter settings. Compared to five other published
      methods and across many image sets, the DAC is found to be faster with better or
      comparable segmentation accuracy.

PMID- 21193810
TI  - Dense mirroring surface recovery from 1D homographies and sparse correspondences.
AB  - In this work, we recover the 3D shape of mirrors, sunglasses, and stainless steel
      implements. A computer monitor displays several images of parallel stripes, each
      image at a different angle. Reflections of these stripes in a mirroring surface
      are captured by the camera. For every image point, the direction of the displayed
      stripes and their reflections in the image are related by a 1D homography matrix,
      computed with a robust version of the statistically accurate heteroscedastic
      approach. By focusing on a sparse set of image points for which monitor-image
      correspondence is computed, the depth and the local shape may be estimated from
      these homographies. The depth estimation relies on statistically correct
      minimization and provides accurate, reliable results. Even for the image points
      where the depth estimation process is inherently unstable, we are able to
      characterize this instability and develop an algorithm to detect and correct it.
      After correcting the instability, dense surface recovery of mirroring objects is
      performed using constrained interpolation, which does not simply interpolate the
      surface depth values but also uses the locally computed 1D homographies to solve
      for the depth, the correspondence, and the local surface shape. The method was
      implemented and the shape of several objects was densely recovered at
      submillimeter accuracy.

PMID- 21193811
TI  - Learning to detect a salient object.
AB  - In this paper, we study the salient object detection problem for images. We
      formulate this problem as a binary labeling task where we separate the salient
      object from the background. We propose a set of novel features, including
      multiscale contrast, center-surround histogram, and color spatial distribution,
      to describe a salient object locally, regionally, and globally. A conditional
      random field is learned to effectively combine these features for salient object
      detection. Further, we extend the proposed approach to detect a salient object
      from sequential images by introducing the dynamic salient features. We collected
      a large image database containing tens of thousands of carefully labeled images
      by multiple users and a video segment database, and conducted a set of
      experiments over them to demonstrate the effectiveness of the proposed approach.

PMID- 21193812
TI  - 3D face reconstruction from a single image using a single reference face shape.
AB  - Human faces are remarkably similar in global properties, including size, aspect
      ratio, and location of main features, but can vary considerably in details across
      individuals, gender, race, or due to facial expression. We propose a novel method
      for 3D shape recovery of faces that exploits the similarity of faces. Our method
      obtains as input a single image and uses a mere single 3D reference model of a
      different person's face. Classical reconstruction methods from single images,
      i.e., shape-from-shading, require knowledge of the reflectance properties and
      lighting as well as depth values for boundary conditions. Recent methods
      circumvent these requirements by representing input faces as combinations (of
      hundreds) of stored 3D models. We propose instead to use the input image as a
      guide to "mold" a single reference model to reach a reconstruction of the sought
      3D shape. Our method assumes Lambertian reflectance and uses harmonic
      representations of lighting. It has been tested on images taken under controlled
      viewing conditions as well as on uncontrolled images downloaded from the
      Internet, demonstrating its accuracy and robustness under a variety of imaging
      conditions and overcoming significant differences in shape between the input and
      reference individuals including differences in facial expressions, gender, and
      race.

PMID- 21193813
TI  - High-resolution three-dimensional 19F-magnetic resonance imaging of rat lung in
      situ: evaluation of airway strain in the perfluorocarbon-filled lung.
AB  - Perfluorocarbons (PFC) are biologically and chemically inert fluids with high
      oxygen and CO(2) carrying capacities. Their use as liquid intrapulmonary gas
      carriers during liquid ventilation has been investigated. We established a method
      of high resolution 3D-(19)F-MRI of the totally PFC-filled lung. The goal of this
      study was to investigate longitudinal and circumferential airway strain in the
      setting of increasing airway pressures on 3D-(19)F-MR images of the PFC-filled
      lung. Sixteen female Wistar rats were euthanized and the liquid perfluorocarbon
      FC-84 instilled into their lungs. 3D-(19)F-MRI was performed at various
      intrapulmonary pressures. Measurements of bronchial length and cross-sectional
      area were obtained from transversal 2D images for each pressure range. Changes in
      bronchial area were used to determine circumferential strain, while longitudinal
      strain was calculated from changes in bronchial length. Our method of 3D-(19)F
      MRI allowed clear visualization of the great bronchi. Longitudinal strain
      increased significantly up to 31.1 cmH(2)O. The greatest strain could be found in
      the range of low airway pressures. Circumferential strain increased strongly with
      the initial pressure rise, but showed no significant changes above 10.4 cmH(2)O.
      Longitudinal strain was generally higher in distal airways, while circumferential
      strain showed no difference. Analysis of mechanical characteristics showed that
      longitudinal and circumferential airway expansion occurred in an anisotropic
      fashion. Whereas longitudinal strain still increased with higher pressures,
      circumferential strain quickly reached a 'strain limit'. Longitudinal strain was
      higher in distal bronchi, as dense PFCs gravitate to dependent, in this case to
      dorso-basal parts of the lung, acting as liquid positive end expiratory pressure.

PMID- 21193814
TI  - Assessment of root-associated paenibacillus polymyxa groups on growth promotion
      and induced systemic resistance in pepper.
AB  - Twenty-nine P. polymyxa strains isolated from rhizospheres of various crops were
      clustered into five genotypic groups on the basis of BOX-PCR analysis. The
      characteristics of several plant growth-promoting factors among the isolates
      revealed the distinct attributes in each allocated group. Under gnotobiotic
      conditions, inoculation of pepper roots with P. polymyxa isolates significantly
      increased the biomass in 17 of total 29 treated plants with untreated plants.
      Experiments on induced systemic resistance (ISR) against bacterial spot pathogen
      Xanthomonas axonopodis pv. vesicatoria in pepper by P. polymyxa strains were
      conducted and only one isolate (KNUC265) was selected. Further studies into ISR
      mediation by the KNUC265 strain against the soft-rot pathogen Erwinia carotovora
      subsp. carotovora in tobacco demonstrated that the tobacco seedlings exposed to
      either bacterial volatiles or diffusible metabolites exhibited a reduction in
      disease severity. In conclusion, ISR and plant growth promotion triggered by P.
      polymyxa isolates were systemically investigated on pepper for the first time.
      The P. polymyxa KNUC265 strain, which elicited both ISR and plant growth
      promotion, could be potentially used in improving the yield of pepper and
      possibly of other crops.

PMID- 21193815
TI  - Genetic and phenotypic diversity of plant growth promoting rhizobacteria isolated
      from sugarcane plants growing in pakistan.
AB  - Bacteria were isolated from roots of sugarcane varieties grown in the fields of
      Punjab. They were identified by using API20E/NE bacterial identification kits and
      from sequences of 16S rRNA and amplicons of the cpn60 gene. The majority of
      bacteria were found to belong to the genera of Enterobacter, Pseudomonas, and
      Klebsiella, but members of genera Azospirillum, Rhizobium, Rahnella, Delftia,
      Caulobacter, Pannonibacter, Xanthomonas, and Stenotrophomonas were also found.
      The community, however, was dominated by members of the Pseudomonadaceae and
      Enterobacteriaceae, as representatives of these genera were found in samples from
      every variety and location examined. All isolates were tested for the presence of
      five enzymes and seven factors known to be associated with plant growth
      promotion. Ten isolates showed lipase activity and eight were positive for
      protease activity. Cellulase, chitinase, and pectinase were not detected in any
      strain. Nine strains showed nitrogen fixing ability (acetylene reduction assay)
      and 26 were capable of solubilizing phosphate. In the presence of 100 mg/l
      tryptophan, all strains except one produced indole acetic acid in the growth
      medium. All isolates were positive for ACC deaminase activity. Six strains
      produced homoserine lactones and three produced HCN and hexamate type
      siderophores. One isolate was capable of inhibiting the growth of 24 pathogenic
      fungal strains of Colletotrichum, Fusarium, Pythium, and Rhizoctonia spp. In
      tests of their abilities to grow under a range of temperature, pH, and NaCl
      concentrations, all isolates grew well on plates with 3% NaCl and most of them
      grew well at 4 to 41degrees C and at pH 11.

PMID- 21193816
TI  - Repressed Quorum sensing by overexpressing LsrR Hampers Salmonella evasion from
      oxidative killing within macrophages.
AB  - Bacterial cell-to-cell communication, termed quorum sensing (QS), leads to
      coordinated group behavior in a cell-density-dependent fashion and controls a
      variety of physiological processes including virulence gene expression. The
      repressor of the lsr operon, LsrR, is the only known regulator of LuxS/AI-2
      mediated QS in Salmonella. Although lack of lsrR did not result in noticeable
      differences in Salmonella survival, the down-regulation of QS as a result of lsrR
      overexpression decreased Salmonella survival within macrophages. We found that
      impaired growth of Salmonella overexpressing lsrR within macrophages was due
      largely to its hypersensitivity to NADPH-dependent oxidative stress. This, in
      turn, was a result of decreased expression of genes involved in the oxidative
      stress response, such as sodA, sodCI, and sodCII, when lsrR was overexpressed.
      These results suggest that down-regulation of QS by excess LsrR can lower
      Salmonella virulence by hampering Salmonella evasion from oxidative killing
      within macrophages.

PMID- 21193817
TI  - Response of Saccharomyces cerevisiae to ethanol stress involves actions of
      protein Asr1p.
AB  - During the fermentation process of Saccharomyces cerevisiae, yeast cells must
      rapidly respond to a wide variety of external stresses in order to survive the
      constantly changing environment, including ethanol stress. The accumulation of
      ethanol can severely inhibit cell growth activity and productivity. Thus, the
      response to changing ethanol concentrations is one of the most important stress
      reactions in S. cerevisiae and worthy of thorough investigation. Therefore, this
      study examined the relationship between ethanol tolerance in S. cerevisiae and a
      unique protein called alcohol sensitive RING/PHD finger 1 protein (Asr1p). A real
      time PCR showed that upon exposure to 8% ethanol, the expression of Asr1 was
      continuously enhanced, reaching a peak 2 h after stimulation. This result was
      confirmed by monitoring the fluorescence levels using a strain with a green
      fluorescent protein tagged to the C-terminal of Asr1p. The fluorescent microscopy
      also revealed a change in the subcellular localization before and after
      stimulation. Furthermore, the disruption of the Asr1 gene resulted in
      hypersensitivity on the medium containing ethanol, when compared with the wild
      type strain. Thus, when taken together, the present results suggest that Asr1 is
      involved in the response to ethanol stress in the yeast S. cerevisiae.

PMID- 21193818
TI  - Comparison of the genomes of deinococcal species using oligonucleotide
      microarrays.
AB  - The bacterium Deinococcus radiodurans is one of the most resistant organisms to
      ionizing radiation and other DNAdamaging agents. Although, at present, 30
      Deinococcus species have been identified, the whole-genome sequences of most
      species remain unknown, with the exception of D. radiodurans (DRD), D.
      geothermalis, and D. deserti. In this study, comparative genomic hybridization
      (CGH) microarray analysis of three Deinococcus species, D. radiopugnans (DRP), D.
      proteolyticus (DPL), and D. radiophilus (DRPH), was performed using
      oligonucleotide arrays based on DRD. Approximately 28%, 14%, and 15% of 3,128
      open reading frames (ORFs) of DRD were absent in the genomes of DRP, DPL, and
      DRPH, respectively. In addition, 162 DRD ORFs were absent in all three species.
      The absence of 17 randomly selected ORFs was confirmed by a Southern blot.
      Functional classification showed that the absent genes spanned a variety of
      functional categories: some genes involved in amino acid biosynthesis, cell
      envelope, cellular processes, central intermediary metabolism, and DNA metabolism
      were not present in any of the three deinococcal species tested. Finally,
      comparative genomic data showed that 120 genes were Deinococcus-specific, not the
      230 reported previously. Specifically, ddrD, ddrO, and ddrH genes, previously
      identified as Deinococcus-specific, were not present in DRP, DPL, or DRPH,
      suggesting that only a portion of ddr genes are shared by all members of the
      genus Deinococcus.

PMID- 21193819
TI  - Purification and characterization of a ubiquitin-like system for autophagosome
      formation.
AB  - Autophagy refers to the bulk degradation of cellular proteins and organelles
      through an autophagosome and plays a pivotal role in the development, cellular
      differentiation, aging, and elimination of aberrant structures. A failure of
      autophagy has been implicated in a growing list of mammalian disease states,
      including cancer and cardiomyopathy. Two ubiquitin-like systems are highly
      involved in autophagy, especially in the formation of autophagosomes. Here, we
      purified and characterized Atg7 (an E1-like enzyme), and Atg3 and Atg10 (E2-like
      enzymes) in order to gain an insight into the role played by ubiquitin-like
      systems in the formation of autophagosomes. Interestingly, we observed that Atg7
      forms a homodimer to construct an active conformation, unlike other E1-like
      enzymes. Although Atg3 was detected as a monomer under physiological conditions,
      Atg10 existed in an oligomeric form, indicating that the mechanism by which Atg10
      functions may differ from that of Atg3.

PMID- 21193820
TI  - Cloning and expression of a thermostable alpha-galactosidase from the
      thermophilic fungus Talaromyces emersonii in the methylotrophic yeast Pichia
      pastoris.
AB  - The first gene (alpha-gal1) encoding an extracellular alpha-Dgalactosidase from
      the thermophilic fungus Talaromyces emersonii was cloned and characterized. The
      alpha-gal1 gene consisted of an open reading frame of 1,792 base pairs
      interrupted by six introns that encoded a mature protein of 452 amino acids,
      including a 24 amino acid secretory signal sequence. The translated protein had
      highest identity with other fungal alpha-galactosidases belonging to glycosyl
      hydrolase family 27. The alpha-gal1 gene was overexpressed as a secretory protein
      with an N-terminal histidine tag in the methylotrophic yeast Pichia pastoris.
      Recombinant alpha-Gal1 was secreted into the culture medium as a monomeric
      glycoprotein with a maximal yield of 10.75 mg/l and purified to homogeneity using
      Hisbinding nickel-agarose affinity chromatography. The purified enzyme was
      maximally active at 70 degrees C, pH 4.5, and lost no activity over 10 days at 50
      degrees C. alpha-Gal1 followed Michaelis-Menten kinetics (Vmax of 240.3
      micronM/min/mg, Km of 0.294 mM) and was inhibited competitively by galactose (Km
      obs of 0.57 mM, Ki of 2.77 mM). The recombinant T. emersonii alpha-galactosidase
      displayed broad substrate preference, being active on both oligo- and polymeric
      substrates, yet had strict specificity for the alpha-galactosidic linkage. Owing
      to its substrate preference and noteworthy stability, alpha-Gal1 is of particular
      interest for possible biotechnological applications involving the processing of
      plant materials.

PMID- 21193821
TI  - Bioproduction and anticancer activity of biosurfactant produced by the
      dematiaceous fungus Exophiala dermatitidis SK80.
AB  - A new biosurfactant producer was isolated from palm-oilcontaminated soil and
      later identified through morphology and DNA sequencing as the yeast-like fungus
      Exophiala dermatitidis. Biosurfactant production was catalyzed by vegetable oil,
      supplemented with a basal medium. The culture conditions that provided the
      biosurfactant with the highest surface activity were found to be 5% palm oil with
      0.08% NH4NO3, at a pH of 5.3, with shaking at 200 rpm, and a temperature of 30
      degrees C for a 14-day period of incubation. The biosurfactant was purified, in
      accordance with surfactant properties, by solvent fractionation using silica gel
      column chromatography. The chemical structure of the strongest surface-active
      compound was elucidated through the use of NMR and mass spectroscopy, and noted
      to be monoolein, which then went on to demonstrate antiproliferative activity
      against cervical cancer (HeLa) and leukemia (U937) cell lines in a dose-dependent
      manner. Interestingly, no cytotoxicity was observed with normal cells even when
      high concentrations were used. Cell and DNA morphological changes, in both cancer
      cell lines, were observed to be cell shrinkage, membrane blebbling, and DNA
      fragmentation.

PMID- 21193822
TI  - Identification of Streptomyces sp. KH29, which produces an antibiotic substance
      processing an inhibitory activity against multidrug-resistant Acinetobacter
      baumannii.
AB  - The Actinomycete strain KH29 is antagonistic to the multidrug-resistant
      Acinetobacter baumannii. Based on the diaminopimelic acid (DAP) type, and the
      morphological and physiological characteristics observed through the use of
      scanning electron microscopy (SEM), KH29 was confirmed as belonging to the genus
      Streptomyces. By way of its noted 16S rDNA nucleotide sequences, KH29 was found
      to have a relationship with Streptomyces cinnamonensis. The production of an
      antibiotic from this strain was found to be most favorable when cultured with
      glucose, polypeptone, and yeast extract (PY) medium for 6 days at 27 degrees C.
      The antibiotic produced was identified, through comparisons with reported
      spectral data including MS and NMR as a cyclo(L-tryptophanyl-L-tryptophanyl).
      Cyclo(L-Trp-L-Trp), from the PY cultures of KH29, was seen to be highly effective
      against 41 of 49 multidrugresistant Acinetobacter baumannii. Furthermore,
      cyclo(LTrp- L-Trp) had antimicrobial activity against Bacillus subtilis,
      Micrococcus luteus, Staphylococcus aureus, Saccharomyces cerevisiae, Aspergillus
      niger, and Candida albicans, However, it was ineffective against Streptomyces
      murinus.

PMID- 21193823
TI  - The effect of protectants and pH changes on the cellular growth and succinic acid
      yield of Mannheimia succiniciproducens LPK7.
AB  - The harmful effects of succinic acid and oxidative stress on cell growth were
      determined during batch fermentation with Mannheimia succiniciproducens LPK7, a
      powerful succinic acid-producing strain, and conditions were optimized to
      minimize these effects. In terms of toxicity, the cell concentration decreased as
      the concentration of succinic acid increased. By changing the pH from 6.5 to 7
      during fermentation, the cell concentration increased by about 10%, and the level
      of succinic acid production was 6% higher than that of the control. In addition,
      by introducing protectants, the cell concentration increased by about 10%, and
      the level of succinic acid produced was increased by 3%.

PMID- 21193824
TI  - Purification and characterization of a thermostable cellobiohydrolase from
      Fomitopsis pinicola.
AB  - A screening for cellobiohydrolase (CBH) activity was performed and Fomitopsis
      pinicola KMJ812 was selected for further characterization as it produced a high
      level of CBH activity. An extracellular CBH was purified to homogeneity by
      sequential chromatography of F. pinicola culture supernatants. The molecular mass
      of the F. pinicola CBH was determined to be 64 kDa by SDS-PAGE and by size
      exclusion chromatography, indicating that the enzyme is a monomer. The F.
      pinicola CBH showed a t1/2 value of 42 h at 70 degrees C and catalytic efficiency
      of 15.8 mM-1 S-1 (kcat/ Km) for p-nitrophenyl-beta-D-cellobioside, one of the
      highest levels seen for CBH-producing microorganisms. Its internal amino acid
      sequences showed a significant homology with hydrolases from glycoside hydrolase
      family 7. Although CBHs have been purified and characterized from other sources,
      the F. pinicola CBH is distinguished from other CBHs by its high catalytic
      efficiency and thermostability.

PMID- 21193825
TI  - Identification and characterization of a pantothenate kinase (PanK-sp) from
      streptomyces peucetius ATCC 27952.
AB  - Pantothenate kinase (PanK) catalyzes the first step in the biosynthesis of the
      essential and ubiquitous cofactor coenzyme A (CoA) in all organisms. Here, we
      report the identification, cloning, and characterization of panK-sp from
      Streptomyces peucetius ATCC 27952. The gene encoded a protein of 332 amino acids
      with a calculated molecular mass of 36.8 kDa and high homology with PanK from S.
      avermitilis and S. coelicolor A3(2). To elucidate the putative function of PanK
      sp, it was cloned into pET32a(+) to construct pPKSP32, and the PanK-sp was then
      expressed in E. coli BL21(DE3) as a His-tag fusion protein and purified by
      immobilized metal affinity chromatography. The enzyme assay of PanK-sp was
      carried out as a coupling assay. The gradual decrease in NADH concentration with
      time clearly indicated the phosphorylating activity of PanK-sp. Furthermore, the
      ca. 1.4-fold increase of DXR and the ca. 1.5-fold increase of actinorhodin by in
      vivo overexpression of panK-sp, constructed in pIBR25 under the control of a
      strong ermE* promoter, established its positive role in secondary metabolite
      production from S. peucetius and S. coelicolor, respectively.

PMID- 21193826
TI  - Repeated Random Mutagenesis of alpha-Amylase from Bacillus licheniformis for
      Improved pH Performance.
AB  - The alpha-amylases activity was improved by random mutagenesis and screening. A
      region comprising residues from the position 34-281 was randomly mutated in B.
      licheniformis alpha-amylase (AmyL), and the library with mutations ranging from
      low, medium, and high frequencies was generated. The library was screened using
      an effective liquid-phase screening method to isolate mutants with an altered pH
      profile. The sequencing of improved variants indicated 2-5 amino acid changes.
      Among them, mutant TP8H5 showed an altered pH profile as compared with that of
      wild type. The sequencing of variant TP8H5 indicated 2 amino acid changes,
      Ile157Ser and Trp193Arg, which were located in the solvent accessible flexible
      loop region in domain B.

PMID- 21193827
TI  - Characterization of yakju brewed from glutinous rice and wild-type yeast strains
      isolated from nuruks.
AB  - Korean traditional rice wines yakju and takju are generally brewed with nuruk as
      the source of the saccharogenic enzymes by natural fermentation. To improve the
      quality of Korean rice wine, the microorganisms in the nuruk need to be studied.
      The objective of this research was to improve the quality of Korean wine with the
      wild-type yeast strains isolated from the fermentation starter, nuruk. Only
      strain YA-6 showed high activity in 20% ethanol. Precipitation of Y89-5-3 was
      similar to that of very flocculent yeast (>80%) at 75.95%. Using 18S rRNA
      sequencing, all 10 strains were identified as Saccharomyces cerevisiae. Volatile
      compounds present in yakju were analyzed by gas chromatography-mass selective
      detector. The principal component analysis (PCA) of the volatile compounds
      grouped long-chain esters on the right side of the first principal component,
      PC1; these compounds were found in yakju that was made with strains YA-6, Y89-5
      3, Y89-5- 2, Y90-9, and Y89-1-1. On the other side of PC1 were short-chain
      esters; these compounds were found in wines that were brewed with strains Y183-2,
      Y268-3, Y54-3, Y98-4, and Y88-4. Overall, the results indicated that using
      different wild-type yeast strains in the fermentation process significantly
      affects the chemical characteristics of the glutinous rice wine.

PMID- 21193828
TI  - Characterization of a Paenibacillus woosongensis beta-Xylosidase/alpha
      Arabinofuranosidase produced by recombinant Escherichia coli.
AB  - A gene encoding the beta-xylosidase/alpha-arabinofuranosidase (XylC) of
      Paenibacillus woosongensis was cloned into Escherichia coli. This xylC gene
      consisted of 1,425 nucleotides, encoding a polypeptide of 474 amino acid
      residues. The deduced amino acid sequence exhibited an 80% similarity with those
      of both Clostridium stercorarium beta-xylosidase/alpha-N-arabinosidase and
      Bacillus cellulosilyticus alpha-arabinofuranosidase, belonging to the glycosyl
      hydrolase family 43. The structural gene was subcloned with a Cterminal His-tag
      into a pET23a(+) expression vector. The His-tagged XylC, purified from a cell
      free extract of a recombinant E. coli BL21(DE3) Codon Plus carrying a xylC gene
      by affinity chromatography, was active on paranitrophenyl- alpha
      arabinofuranoside (pNPA) as well as paranitrophenyl- beta-xylopyranoside (pNPX).
      However, the enzymatic activities for the substrates were somewhat incongruously
      influenced by reaction pHs and temperatures. The enzyme was also affected by
      various chemicals at different levels. SDS (5 mM) inhibited the enzymatic
      activity for pNPX, while enhancing the enzymatic activity for pNPA. Enzyme
      activity was also found to be inhibited by addition of pentose or hexose. The
      Michaelis constant and maximum velocity of the purified enzyme were determined
      for hydrolysis of pNPX and pNPA, respectively.

PMID- 21193830
TI  - Cold-adapted and rhizosphere-competent strain of Rahnella sp. with broad-spectrum
      plant growth-promotion potential.
AB  - A phosphate-solubilizing bacterial strain isolated from Hippophae rhamnoides
      rhizosphere was identified as Rahnella sp. based on its phenotypic features and
      16S rRNA gene sequence. The bacterial strain showed the growth characteristics of
      a cold-adapted psychrotroph, with the multiple plant growth-promoting traits of
      inorganic and organic phosphate solubilization, 1-aminocyclopropane-1-
      carboxylate-deaminase activity, ammonia generation, and siderophore production.
      The strain also produced indole- 3-acetic acid, indole-3-acetaldehyde, indole-3
      acetamide, indole-3-acetonitrile, indole-3-lactic acid, and indole-3- pyruvic
      acid in tryptophan-supplemented nutrient broth. Gluconic, citric and isocitric
      acids were the major organic acids detected during tricalcium phosphate
      solubilization. A rifampicin-resistant mutant of the strain exhibited high
      rhizosphere competence without disturbance to the resident microbial populations
      in pea rhizosphere. Seed bacterization with a charcoal-based inoculum
      significantly increased growth in barley, chickpea, pea, and maize under the
      controlled environment. Microplot testing of the inoculum at two different
      locations in pea also showed significant increase in growth and yield. The
      attributes of coldtolerance, high rhizosphere competence, and broad-spectrum
      plant growth-promoting activity exhibited the potential of Rahnella sp. BIHB 783
      for increasing agriculture productivity.

PMID- 21193831
TI  - Mutations in the gyrB, parC, and parE genes of quinolone-resistant isolates and
      mutants of Edwardsiella tarda.
AB  - The full length genes gyrB (2,415 bp), parC (2,277 bp), and parE (1,896 bp) in
      Edwardsiella tarda were cloned by PCR with degenerate primers based on the
      sequence of the respective quinolone resistance-determining region (QRDR),
      followed by elongation of 5' and 3' ends using cassette ligation-mediated PCR
      (CLMP). Analysis of the cloned genes revealed open reading frames (ORFs) encoding
      proteins of 804 (GyrB), 758 (ParC), and 631 (ParE) amino acids with conserved
      gyrase/topoisomerase features and motifs important for enzymatic function. The
      ORFs were preceded by putative promoters, ribosome binding sites, and inverted
      repeats with the potential to form cruciform structures for binding of DNA
      binding proteins. When comparing the deduced amino acid sequences of E. tarda
      GyrB, ParC, and ParE with those of the corresponding proteins in other bacteria,
      they were found to be most closely related to Escherichia coli GyrB (87.6%
      identity), Klebsiella pneumoniae ParC (78.8% identity) and Salmonella typhimurium
      ParE (89.5% identity), respectively. The two topoisomerase genes, parC and parE,
      were found to be contiguous on the E. tarda chromosome. All 18 quinoloneresistant
      isolates obtained from Korea thus far did not contain subunit alternations apart
      from a substitution in GyrA (Ser83->Arg). However, an alteration in the QRDR of
      ParC (Ser84->Ile) following an amino acid substitution in GyrA (Asp87->Gly) was
      detected in E. tarda mutants selected in vitro at 8 microng/ml ciprofloxacin
      (CIP). A mutant with a GyrB (Ser464->Leu) and GyrA (Asp87->Gly) substitution did
      not show a significant increase in the minimum inhibitory concentration (MIC) of
      CIP. None of the in vitro mutants exhibited mutations in parE. Thus, gyrA and
      parC should be considered to be the primary and secondary targets, respectively,
      of quinolones in E. tarda.

PMID- 21193832
TI  - Gibberellin-producing endophytic fungi isolated from Monochoria vaginalis.
AB  - The role of endophytic fungi in plant growth and development is well documented.
      However, endophytic fungi with growth promotion capacity have never been isolated
      from weeds previously. In the current study, we isolated 8 fungal endophytes from
      the roots of Monochoria vaginalis, a serious weed of rice paddy in Korea. These
      isolates were screened on Waito-C, in order to identify plant growth promoting
      metabolites. Two fungal isolates (M5.A & M1.5) significantly promoted the plant
      height and shoot length of Waito-C during preliminary screening experiments. The
      culture filtrates (CFs) of M5.A and M1.5 also promoted the shoot length of
      Echinocloa crusgalli. Gibberellins (GAs) analysis of the CFs of M5.A and M1.5
      showed that these endophytic fungi secrete higher quantities of GAs as compared
      with wild-type G. fujikuroi KCCM12329. The CF of M5.A contained bioactive GAs
      (GA3, 2.8 ng/ml; GA4, 2.6 ng/ml, and GA7, 6.68 ng/ml) in conjunction with
      physiologically inactive GA9 (1.61 ng/ml) and GA24 (0.18 ng/ml). The CF of M1.5
      contained physiologically active GAs (GA3, 1.64 ng/ml; GA4, 1.37 ng/ml and GA7,
      6.29 ng/ml) in conjunction with physiologically inactive GA9 (3.44 ng/ml), GA12
      (0.3 ng/ml), and GA24 (0.59 ng/ml). M5.A and M1.5 were identified as new strains
      of Penicillium sp. and Aspergillus sp., respectively, based on their 18S rDNA
      sequence homology and phylogenetic analysis.

PMID- 21193833
TI  - A genetic comparison of Brucella abortus isolates from animals and humans by
      using an MLVA assay.
AB  - The MLVA assay is known to have a high ability to identify and discriminate
      Brucella species, so that it can be used as an epidemiological tool to
      discriminate Brucella isolates originating from restricted geographic sources. In
      this study, the genetic profiles of 38 B. abortus isolates from humans were
      analyzed and compared with genotypes from animal isolates in South Korea. As a
      result, it was found that they did not show high genetic diversity and were
      compacted. They were clustered together with animal isolates, showing a
      significant correlation to regional distributions. With its ability to prove a
      significant genetic correlation among B. abortus isolates from animals and humans
      in South Korea, the MLVA assay could be utilized as part of a program to control
      and eradicate brucellosis, one of the major zoonoses. This study represents the
      first data of genetic correlation of B. abortus isolates from humans and animals
      in South Korea.

PMID- 21193834
TI  - Antigenicity of partial fragments of recombinant Pasteurella multocida toxin.
AB  - Pasteurella multocida serogroup D strain, which produces P. multocida toxin
      (PMT), is a widespread and harmful pathogen of respiratory diseases such as
      pneumonia and progressive atrophic rhinitis (PAR) in swine. Vaccination has been
      considered the most desirable and effective approach for controlling the diseases
      caused by toxigenic P. multocida. To investigate the antigenicity and
      immunogenicity of partial fragments of recombinant PMT, recombinant proteins of
      the N-terminal (PMT-A), middle (PMT-B), Cterminal (PMT-C), and middle-C-terminal
      (PMT2.3) regions of PMT were successfully produced in an Escherichia coli
      expression system. The molecular masses of PMT-A, PMT-B, PMT-C, and PMT2.3 were
      ca. 53, 55, 35, and 84 kDa, respectively, purified by nickel-nitrilotriacetic
      acid (Ni-NTA) affinity column chromatography. All the recombinant proteins except
      for PMT-A showed immune responses to antisera obtained from a swine showing
      symptoms of PAR. Moreover, high titers of PMT-specific antibodies were raised
      from mice immunized with each of the recombinant proteins; however, the
      immunoreactivities of the antibodies to authentic PMT and heat-inactivated whole
      bacteria were different, respectively. In the protection study, the highest
      protection against homologous challenge was shown in the case of PMT2.3;
      relatively poor protections occurred for the other PMT fragments.

PMID- 21193829
TI  - Bacterial community composition and diversity of a full-scale integrated fixed
      film activated sludge system as investigated by pyrosequencing.
AB  - The integrated fixed-film activated sludge (IFAS) system is a variation of the
      activated sludge wastewater treatment process, in which hybrid suspended and
      attached biomass is used to treat wastewater. Although the function and
      performance of the IFAS system are well studied, little is known about its
      microbial community structure. In this study, the composition and diversity of
      the bacterial community of suspended and attached biomass samples were
      investigated in a full-scale IFAS system using a highthroughput pyrosequencing
      technology. Distinct bacterial community compositions were examined for each
      sample and appeared to be important for its features different from conventional
      activated sludge processes. The abundant bacterial groups were Betaproteobacteria
      (59.3%), Gammaproteobacteria (8.1%), Bacteroidetes (5.2%), Alphaproteobacteria
      (3.9%), and Actinobacteria (3.2%) in the suspended sample, whereas Actinobacteria
      (14.6%), Firmicutes (13.6%), Bacteroidetes (11.6%), Betaproteobacteria (9.9%),
      Gammaproteobacteria (9.25%), and Alphaproteobacteria (7.4%) were major bacterial
      groups in the attached sample. Regarding the diversity, totals of 3,034 and 1,451
      operational taxonomic units were identified at the 3% cutoff for the suspended
      and attached samples, respectively. Rank abundance and community analyses
      demonstrated that most of the diversity was originated from rare species in the
      samples. Taken together, the information obtained in this study will be a base
      for further studies relating to the microbial community structure and function of
      the IFAS system.

PMID- 21193835
TI  - Antibiotic resistance profiles of Staphylococcus pseudintermedius isolates from
      canine patients in Korea.
AB  - In this study, the prevalence of antibiotic resistance was examined among 74
      Staphylococcus pseudintermedius strains recently isolated from clinical cases of
      canine pyoderma and otitis externa at the veterinary teaching hospital at Konkuk
      University, Korea. Bacterial resistance to the nine commonly used antibiotics was
      evaluated by a standard disk diffusion technique based on the guidelines of the
      Clinical and Laboratory Standards Institute. The results demonstrated that most
      S. pseudintermedius isolates were resistant to penicillin (95.9%) or tetracycline
      (91.9%), but highly susceptible to amoxicillin/clavulanic acid (90.5%). Among the
      74 isolates, 13 mecA-positive and methicillin-resistant S. pseudintermedius
      (MRSP) strains were identified, displaying a high level of resistance (84.6-
      100%) to each of the individual antibiotics evaluated, with the exception of
      amoxicillin/clavulanic acid (46.2% resistance). Notably, all of the MRSP isolates
      exhibited simultaneous resistance to four or more different antibiotics,
      indicating that they are multiple drug resistant (MDR) strains. Taken together,
      these results imply that more careful selection or prescription of antibiotics
      for canine pyoderma and otitis externa should be required for reducing the
      emergence and/or spread of MDR strains, especially MDR-MRSP isolates, in
      veterinary pet clinics in Korea.

PMID- 21193836
TI  - Selection of peptides binding to HCV e2 and inhibiting viral infectivity.
AB  - The envelope glycoprotein E2 of hepatitis C virus (HCV) binds to various cell
      surface receptors for viral infection. We performed biopanning against this
      protein and selected peptides from phage display peptide libraries. Two short
      peptides, pep7-1 and pep12-1, were selected and their ability to inhibit the
      infection process was investigated. When pep7-1 was present, the infectivity of
      HCV particles in cell culture was notably decreased. This decrease was
      demonstrated by Western blot analysis, immunofluorescence assay, and reverse
      transcription PCR assay. However, pep12-1 showed little inhibitory effect on HCV
      infection.

PMID- 21193837
TI  - Rapamycin treatment augments motor neuron degeneration in SOD1(G93A) mouse model
      of amyotrophic lateral sclerosis.
AB  - Aberrant protein misfolding may contribute to the pathogenesis of amyotrophic
      lateral sclerosis (ALS) but the detailed mechanisms are largely unknown. Our
      previous study has shown that autophagy is altered in the mouse model of ALS. In
      the present study, we systematically investigated the correlation of the
      autophagic alteration with the motor neurons (MNs) degeneration in the ALS mice.
      We have demonstrated that the autophagic protein marker LC3-II is markedly and
      specifically increased in the spinal cord MNs of the ALS mice. Electron
      microscopy and immunochemistry studies have shown that autophagic vacuoles are
      significantly accumulated in the dystrophic axons of spinal cord MNs of the ALS
      mice. All these changes in the ALS mice appear at the age of 90 d when the ALS
      mice display modest clinical symptoms; and they become prominent at the age of
      120 d. The clinical symptoms are correlated with the progression of MNs
      degeneration. Moreover, we have found that p62/SQSTM1 is accumulated
      progressively in the spinal cord, indicating that the possibility of impaired
      autophagic flux in the SOD1(G93A) mice. Furthermore, to our surprise, we have
      found that treatment with autophagy enhancer rapamycin accelerates the MNs
      degeneration, shortens the life span of the ALS mice, and has no obvious effects
      on the accumulation of SOD1 aggregates. In addition, we have demonstrated that
      rapamycin treatment in the ALS mice causes more severe mitochondrial impairment,
      higher Bax levels and greater caspase-3 activation. These findings suggest that
      selective degeneration of MNs is associated with the impairment of the autophagy
      pathway and that rapamycin treatment may exacerbate the pathological processing
      through apoptosis and other mechanisms in the ALS mice.

PMID- 21193838
TI  - PCL2 modulates gene regulatory networks controlling self-renewal and commitment
      in embryonic stem cells.
AB  - Recent reports have better elucidated the components of the Polycomb Repressive
      Complex 2 (PRC2) and its functional role in embryonic stem cells (ESCs) and their
      differentiated derivatives. The depletion of a newly described mammalian PRC2
      associated protein, PCL2, leads to an increase in ESC self-renewal and a delay in
      differentiation, a phenotype similar to knockouts of the core PRC2 members.
      Genomic and cell biology data suggest that PCL2 is important in cell fate
      decisions and may play a role in recruitment of PRC2 to target genes and histone
      methylation. Importantly, depletion of PCL2 in ESCs leads to a decrease in
      3meH3K27 at the proximal promoter regions of pluripotency transcription factors
      Tbx3, Klf4, Foxd3 and a concomitant increase in gene expression. These proteins
      subsequently activate expression of Oct4, Nanog and Sox2 through a feed-forward
      gene regulatory circuit, altering the core pluripotency network and driving cell
      fate decisions towards self-renewal. We propose a model whereby alteration of the
      epigenetic state of Tbx3, Klf4, and Foxd3 results in the enforced expression of
      the pluripotency network, preventing differentiation.

PMID- 21193840
TI  - Autophagy targeting of Listeria monocytogenes and the bacterial countermeasure.
AB  - Autophagy acts as an intrinsic defense system against intracellular bacterial
      survival. Recently, multiple cellular pathways that target intracellular
      bacterial pathogens to autophagy have been described. These include the Atg5/LC3
      pathway, which targets Shigella, the ubiquitin (Ub)-NDP52-LC3 pathway, which
      targets Group A Streptococcus (GAS) and Salmonella typhimurium, the Ub-p62-LC3
      pathway, which targets Mycobacterium tuberculosis, Listeria monocytogenes and S.
      typhimurium, and the diacylglycerol-dependent pathway, which targets S.
      typhimurium. In addition, the bacterial invasion process is targeted by the NOD1
      or NOD2-Atg16LLC3 pathway. Bacterial pathogens with an intracytosolic lifestyle,
      i.e., those capable of inducing actin polymerization and cell-to-cell spreading,
      also employ diverse tactics to evade autophagic recognition. Thus, Shigella, L.
      monocytogenes and Burkholderia pseudomallei deploy highly evolved systems to
      evade autophagic recognition and growth restriction. Here, we briefly review
      current knowledge of host recognition of L. monocytogenes by the innate immune
      system, and highlight how autophagic recognition by the host is overcome by
      bacterial countermeasures.

PMID- 21193839
TI  - A polymeric nanoparticle formulation of curcumin inhibits growth, clonogenicity
      and stem-like fraction in malignant brain tumors.
AB  - Curcumin is a polyphenolic compound derived from the Indian spice turmeric. We
      used nanoparticle-encapsulated curcumin to treat medulloblastoma and glioblastoma
      cells. This formulation caused a dose-dependent decrease in growth of multiple
      brain tumor cell cultures, including the embryonal tumor derived lines DAOY and
      D283Med, and the glioblastoma neurosphere lines HSR-GBM1 and JHH-GBM14. The
      reductions in viable cell mass observed were associated with a combination of
      G(2)/M arrest and apoptotic induction. Curcumin also significantly decreased
      anchorage-independent clonogenic growth and reduced the CD133-positive stem-like
      population. Down-regulation of the insulin-like growth factor pathway in DAOY
      medulloblastoma cells was observed, providing one possible mechanism for the
      changes. Levels of STAT3 were also attenuated. Hedgehog signaling was blocked in
      DAOY cells but Notch signaling was not inhibited. Our data suggest that curcumin
      nanoparticles can inhibit malignant brain tumor growth through the modulation of
      cell proliferation, survival and stem cell phenotype.

PMID- 21193841
TI  - How cells deploy ubiquitin and autophagy to defend their cytosol from bacterial
      invasion.
AB  - Autophagy serves as a cell-autonomous effector mechanism of innate immunity in
      the cytosol. Autophagy restricts bacterial proliferation by separating bacteria
      from the nutrient-rich cytosol and delivering them into bactericidal
      autolysosomes. Autophagy also restricts inflammation by enclosing the membrane
      remnants of vacuoles from which bacteria have escaped. In contrast to starvation
      induced autophagy, which engulfs cytosol nonspecifically, antibacterial autophagy
      is receptor-mediated and selective. Several distinct pathways of antibacterial
      autophagy have been identified recently, which can be triggered by either
      bacterial PAMPs, host-mediated modifications of bacteria-containing vacuoles, or
      cytosolic bacteria that have become decorated with ubiquitin. Ubiquitin-coated
      bacteria are sensed by p62, a promiscuous autophagy receptor required for the
      uptake of a variety of ubiquitin-marked autophagy substrates, and by NDP52, an
      autophagy receptor that, by associating with the immunoregulatory kinase TBK1,
      may serve a dedicated function in cytosolic immunity.

PMID- 21193842
TI  - PDRG1, a novel tumor marker for multiple malignancies that is selectively
      regulated by genotoxic stress.
AB  - We have previously cloned and characterized a novel p53 and DNA damage-regulated
      gene named PDRG1. PDRG1 was found to be differentially regulated by ultraviolet
      (UV) radiation and p53. In this study, we further investigated stress regulation
      of PDRG1 and found it to be selectively regulated by agents that induce genotoxic
      stress (DNA damage). Using cancer profiling arrays, we also investigated PDRG1
      expression in matching normal and tumor samples representing various malignancies
      and found its expression to be upregulated in multiple malignancies including
      cancers of the colon, rectum, ovary, lung, stomach, breast and uterus when
      compared to their respective matched normal tissues. Western blot and
      immunohistochemical analyses were also performed on select specimen sets of colon
      cancers and matching normal tissues and the results also indicated PDRG1
      overexpression in tumors relative to normal tissues. To gain insight into the
      function of PDRG1, we performed PDRG1 knockdown in human colon cancer cells and
      found its depletion to result in marked slowdown of tumor cell growth. These
      results suggest that PDGR1 may be linked to cell growth regulation. Yeast two
      hybrid screen also led to the identification of PDCD7, CIZ1 and MAP1S as PDRG1
      interacting proteins that are involved in apoptosis and cell cycle regulation
      which further implicate PDRG1 in controlling cell growth regulation. Taken
      together, our results indicate that PDRG1 expression is increased in multiple
      human malignancies suggesting it to be a high-value novel tumor marker that could
      play a role in cancer development and/or progression.

PMID- 21193843
TI  - Go get your dream job.

PMID- 21193844
TI  - Casbane diterpene as a promising natural antimicrobial agent against biofilm
      associated infections.
AB  - Croton nepetaefolius is a native plant from northeastern Brazil that belongs to
      the Euphorbiaceae family. The biological action of this plant has been
      extensively explored, being the secondary metabolites responsible for its
      properties alkaloids, diterpenes, and triterpenes. This study aimed to evaluate
      the ability of casbane diterpene (CD), isolated from the ethanolic extract of C.
      nepetaefolius, to inhibit microbial growth and biofilm formation of several
      clinical relevant species (bacteria and yeasts). It was found that CD possessed
      biocidal and biostatic activity against the majority of the species screened,
      with minimal active concentrations ranging between 125 and 500 ug/mL. In
      addition, it was observed that biofilm formation was inhibited even when the
      planktonic growth was not significantly affected. In conclusion, CD showed
      potential to be a natural tool for the treatment of diseases caused by different
      infectious microorganisms.

PMID- 21193845
TI  - Small molecule inhibitors as countermeasures for botulinum neurotoxin
      intoxication.
AB  - Botulinum neurotoxins (BoNTs) are the most potent of known toxins and are listed
      as category A biothreat agents by the U.S. CDC. The BoNT-mediated proteolysis of
      SNARE proteins inhibits the exocytosis of acetylcholine into neuromuscular
      junctions, leading to life-threatening flaccid paralysis. Currently, the only
      therapy for BoNT intoxication (which results in the disease state botulism)
      includes experimental preventative antibodies and long-term supportive care.
      Therefore, there is an urgent need to identify and develop inhibitors that will
      serve as both prophylactic agents and post-exposure 'rescue' therapeutics. This
      review focuses on recent progress to discover and develop small molecule
      inhibitors as therapeutic countermeasures for BoNT intoxication.

PMID- 21193846
TI  - Targeting cell entry of enveloped viruses as an antiviral strategy.
AB  - The entry of enveloped viruses into their host cells involves several successive
      steps, each one being amenable to therapeutic intervention. Entry inhibitors act
      by targeting viral and/or cellular components, through either the inhibition of
      protein-protein interactions within the viral envelope proteins or between viral
      proteins and host cell receptors, or through the inhibition of protein-lipid
      interactions. Interestingly, inhibitors that concentrate into/onto the membrane
      in order to target a protein involved in the entry process, such as arbidol or
      peptide inhibitors of the human immunodeficiency virus (HIV), could allow the use
      of doses compatible with therapeutic requirements. The efficacy of these drugs
      validates entry as a point of intervention in viral life cycles. Strategies based
      upon small molecule antiviral agents, peptides, proteins or nucleic acids, would
      most likely prove efficient in multidrug combinations, in order to inhibit
      several steps of virus life cycle and prevent disease progression.

PMID- 21193847
TI  - Phenolic compounds in Brassica vegetables.
AB  - Phenolic compounds are a large group of phytochemicals widespread in the plant
      kingdom. Depending on their structure they can be classified into simple phenols,
      phenolic acids, hydroxycinnamic acid derivatives and flavonoids. Phenolic
      compounds have received considerable attention for being potentially protective
      factors against cancer and heart diseases, in part because of their potent
      antioxidative properties and their ubiquity in a wide range of commonly consumed
      foods of plant origin. The Brassicaceae family includes a wide range of
      horticultural crops, some of them with economic significance and extensively used
      in the diet throughout the world. The phenolic composition of Brassica vegetables
      has been recently investigated and, nowadays, the profile of different Brassica
      species is well established. Here, we review the significance of phenolic
      compounds as a source of beneficial compounds for human health and the influence
      of environmental conditions and processing mechanisms on the phenolic composition
      of Brassica vegetables.

PMID- 21193848
TI  - An efficient new route to dihydropyranobenzimidazole inhibitors of HCV
      replication.
AB  - A class of dihydropyranobenzimidazole inhibitors was recently discovered that
      acts against the hepatitis C virus (HCV) in a new way, binding to the IRES-IIa
      subdomain of the highly conserved 5' untranslated region of the viral RNA and
      thus preventing the ribosome from initiating translation. However, the reported
      synthesis of these compounds is lengthy and low-yielding, the intermediates are
      troublesome to purify, and the route is poorly structured for the creation of
      libraries. We report a streamlined route to this class of inhibitors in which
      yields are far higher and most intermediates are crystalline. In addition, a key
      variable side chain is introduced late in the synthesis, allowing analogs to be
      easily synthesized for optimization of antiviral activity.

PMID- 21193850
TI  - Plasma pentraxin3 and arterial stiffness in men with obstructive sleep apnea.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) induces inflammation and vascular
      damage that might contribute to an increased risk of cardiovascular disease
      (CVD). However, the mechanisms linking OSA and CVD are not fully understood.
      Pentraxin3 may play a significant role in vascular inflammation and damage.
      Currently, there is lack of data on pentraxin3 and its role in vascular damage
      associated with OSA. METHODS: We enrolled 50 males with OSA and 25 controls
      matched for age and body mass index (BMI). Patients with OSA were further divided
      into mild and moderate to severe groups. We measured plasma pentraxin3 and
      evaluated vascular damage using an arterial stiffness parameter--the cardio-ankle
      vascular index (CAVI)--in all subjects. In the moderate to severe OSA group,
      pentraxin3 and CAVI were repeatedly measured following continuous positive airway
      pressure (CPAP) therapy for 1 month. RESULTS: Pentraxin3 levels in the moderate
      to-severe OSA group were significantly higher than those in the mild OSA and
      control groups, with median levels (25th-75th percentile) of 2.36 (1.79-2.78),
      1.63 (1.15-2.05), and 1.53 (1.14-2.04) ng/ml, respectively (P < 0.01). Pentraxin3
      level was independently correlated with CAVI (coefficient, 0.34 P < 0.01). In the
      moderate-to-severe OSA group, pentraxin3 and CAVI levels were significantly
      reduced (P < 0.01 and P = 0.04, respectively) after 1 month of CPAP therapy.
      CONCLUSIONS: Plasma pentraxin3 and arterial stiffness levels in the moderate-to
      severe OSA group were greater than the corresponding levels in patients without
      OSA. However, pentraxin3 level can be managed by CPAP therapy for OSA.

PMID- 21193851
TI  - Association of the LCT-13910C>T polymorphism with obesity and its modulation by
      dairy products in a Mediterranean population.
AB  - The -13910C>T polymorphism (rs4988235) upstream from the lactase (LCT) gene,
      strongly associated with lactase persistence (LP) in Europeans, is emerging as a
      new candidate for obesity. We aimed to analyze the association of this
      polymorphism with obesity-related variables and its modulation by dairy product
      intake in an elderly population. We studied 940 high-cardiovascular risk Spanish
      subjects (aged 67 +/- 7 years). Dairy product consumption was assessed by a
      validated questionnaire. Anthropometric variables were directly measured, and
      metabolic syndrome-related variables were obtained. Prevalence of genotypes was:
      38.0% CC (lactase nonpersistent (LNP)), 45.7% CT, and 16.3% TT. The CC genotype
      was not associated with lower milk or dairy product consumption in the whole
      population. Only in women was dairy intake significantly lower in CC subjects.
      The most important association was obtained with anthropometric measurements. CC
      individuals had lower weight (P = 0.032), lower BMI (29.7 +/- 4.2 vs. 30.6 +/-
      4.2 kg/m(2); P = 0.003) and lower waist circumference (101.1 +/- 11.8 vs. 103.5
      +/- 11.5 cm; P = 0.005) than T-allele carriers. Obesity risk was also
      significantly higher in T-allele carriers than in CC individuals (odds ratio
      (OR): 1.38; 95% confidence interval (CI): 1.05-1.81; P = 0.01), and remained
      significant even after adjustment for sex, age, diabetes, physical activity, and
      energy intake. However, in subgroup analysis, these associations were found to be
      significant only among those consuming moderate or high lactose intakes (>8
      g/day). No significant associations with lipids, glucose, or blood pressure were
      obtained after adjustment for BMI. In conclusion, despite not finding marked
      differences in dairy product consumption, this polymorphism was strongly
      associated with BMI and obesity and modulated by lactose intake in this
      Mediterranean population.

PMID- 21193852
TI  - Hip-Hop to Health Jr. Obesity Prevention Effectiveness Trial: postintervention
      results.
AB  - The preschool years offer an opportunity to interrupt the trajectory toward
      obesity in black children. The Hip-Hop to Health Jr. Obesity Prevention
      Effectiveness Trial was a group-randomized controlled trial assessing the
      feasibility and effectiveness of a teacher-delivered weight control intervention
      for black preschool children. The 618 participating children were enrolled in 18
      schools administered by the Chicago Public Schools. Children enrolled in the nine
      schools randomized to the intervention group received a 14-week weight control
      intervention delivered by their classroom teachers. Children in the nine control
      schools received a general health intervention. Height and weight, physical
      activity, screen time, and diet data were collected at baseline and
      postintervention. At postintervention, children in the intervention schools
      engaged in more moderate-to-vigorous physical activity (MVPA) than children in
      the control schools (difference between adjusted group means = 7.46 min/day, P =
      0.02). Also, children in the intervention group had less total screen time (-27.8
      min/day, P = 0.05). There were no significant differences in BMI, BMI Z score, or
      dietary intake. It is feasible to adapt an obesity prevention program to be
      taught by classroom teachers. The intervention showed positive influences on
      physical activity and screen time, but not on diet. Measuring diet and physical
      activity in preschool children remains a challenge, and interventions delivered
      by classroom teachers require both intensive initial training and ongoing
      individualized supervision.

PMID- 21193854
TI  - Evolution of regulatory frameworks.

PMID- 21193853
TI  - Amyloid-beta and tau--a toxic pas de deux in Alzheimer's disease.
AB  - Amyloid-beta and tau are the two hallmark proteins in Alzheimer's disease.
      Although both amyloid-beta and tau have been extensively studied individually
      with regard to their separate modes of toxicity, more recently new light has been
      shed on their possible interactions and synergistic effects in Alzheimer's
      disease. Here, we review novel findings that have shifted our understanding of
      the role of tau in the pathogenesis of Alzheimer's disease towards being a
      crucial partner of amyloid-beta. As we gain a deeper understanding of the
      different cellular functions of tau, the focus shifts from the axon, where tau
      has a principal role as a microtubule-associated protein, to the dendrite, where
      it mediates amyloid-beta toxicity.

PMID- 21193855
TI  - Suspense builds on anti-obesity rollercoaster ride.

PMID- 21193857
TI  - Trial watch: hope renewed for strategy to raise HDL cholesterol.

PMID- 21193858
TI  - Market watch: upcoming market catalysts in Q1 2011.

PMID- 21193859
TI  - Patent watch: the patent cliff steepens.

PMID- 21193860
TI  - Data exclusivity for biologics.

PMID- 21193861
TI  - Pegloticase.

PMID- 21193862
TI  - Anticancer drugs: blocking phospholipid-protein interactions.

PMID- 21193863
TI  - Stroke: removing restraints on recovery.

PMID- 21193864
TI  - Analgesia: lipid linked to improved opiate therapy.

PMID- 21193865
TI  - Anticancer drugs: stapled peptide rescues p53.

PMID- 21193866
TI  - Metabolic disease: GOAT inhibitors to battle the bulge?

PMID- 21193869
TI  - The relevance of assessment of intestinal P-gp inhibition using digoxin as an in
      vivo probe substrate.

PMID- 21193870
TI  - Can we increase our life span? The role of nuclear gerontology.
AB  - Elderly people, those above 60 or 65 years old differ from younger people in many
      ways. Nuclear medicine can play a role in the diagnosis of diseases of the
      elderly and thus help, in social adjustment and in care for the elderly people.
      The question is why adult stem cells have a certain limit of reproduction, since
      their DNA in a normal physical environment can theoretically live very much
      longer. The elderly are prone to suffer more diseases than the young. It is
      important that the elderly should use water soluble and not lipid soluble drugs.
      There are many more to write about the elderly. We have tried to be brief in
      order to show the importance of using nuclear medicine in gerontology. Let us
      mention here that the word gerontology means in greek "talk about the elderly"
      (gerontas is the old man and logy is to talk about). Elderly people are a large
      part of our society and we do have every reason, every interest and
      responsibility to keep this part of our society healthy, useful and productive.

PMID- 21193871
TI  - Acute effects of recombinant human TSH on bone markers in differentiated thyroid
      cancer.
AB  - Patients suffering from differentiated thyroid cancer receive suppressive of TSH
      thyroxine treatment of long duration. This study was undertaken to determine
      changes on bone serum markers after administration of recombinant human TSH in
      differentiated thyroid cancer patients on thyroxine treatment. Forty-five
      patients undergoing diagnostic evaluation of their disease and 48 matched
      controls were investigated: two injections of 0.9 mg of recombinant human TSH
      were given to the patients (on days 1 and 2). Blood samples were collected the
      day before first injection (day 0) and days 3, 5 and 10 after recombinant human
      TSH administration. Blood samples were obtained for serum TSH, bone alkaline
      phosphatase, osteocalcin, osteoprotegerin, receptor activator of nuclear factor
      kB ligand and bone tartrate resistant acid phosphatase. Recombinant human TSH
      induced a significant increase in bone alkaline phosphatase on day 3 up to day 10
      in postmenopausal women. A statistically significant increase was also observed
      in serum receptor activator of nuclear factor kB ligand in both men and
      postmenopausal women on day 3 while on day 10 these values returned to baseline
      levels. No significant effects were seen in other parameters at any time of the
      investigation. In conclusion, we demonstrated significant increases in receptor
      activator of nuclear factor kB ligand and bone alkaline phosphatase after TSH
      stimulation. The changes in these bone indices were more prominent in the group
      of postmenopausal women.

PMID- 21193872
TI  - Tissue polypeptide antigen in the follow-up of patients with urinary bladder
      cancer compared with conventional urine cytology.
AB  - The incidence of bladder cancer has demonstrated a rapid increase during the last
      decades. The aim of this study is to determine the clinical value of serum tissue
      polypeptide antigen (TPA) as a tumour marker for urinary bladder cancer in
      comparison with conventional urine cytology. Urine and blood samples were
      obtained from a total of 108 patients (group A) with a known history of bladder
      cancer, who presented for their routine 3 month follow-up. These 108 patients
      included 45 patients with high grade and 63 patients with low grade bladder
      cancer, and 30 patients with lower urinary tract symptoms (LUTS) and no history
      of bladder cancer (group B). Urine and blood samples from fifty healthy adults
      (group C) were also tested; this group served as the control group for estimating
      the normal range of serum TPA values. In all group A patients cystoscopy and/or
      bladder biopsies were performed. All blood and urine samples were tested for TPA
      and conventional urine cytology respectively. Results showed that the upper
      normal range for TPA was 1.0 ng/mL(0.9 +/- 0.04) in the control group. For the
      subgroups of patients with high and low grade bladder cancer elevated serum TPA
      levels were found in 52% and 40% of the patients respectively. The overall serum
      TPA sensitivity and specificity were 50% and 85% respectively for patients with
      known bladder cancer (group A). We found the sensitivity of cytology for high
      grade bladder (GIII) carcinomas to be 72%; however when urine cytology was
      combined with serum TPA the overall sensitivity reached 80%. We conclude that
      serum TPA combined with urine cytology may be used as a prognostic marker for
      bladder cancer.

PMID- 21193867
TI  - G protein-coupled receptors: novel targets for drug discovery in cancer.
AB  - G protein-coupled receptors (GPCRs) belong to a superfamily of cell surface
      signalling proteins that have a pivotal role in many physiological functions and
      in multiple diseases, including the development of cancer and cancer metastasis.
      Current drugs that target GPCRs - many of which have excellent therapeutic
      benefits - are directed towards only a few GPCR members. Therefore, huge efforts
      are currently underway to develop new GPCR-based drugs, particularly for cancer.
      We review recent findings that present unexpected opportunities to interfere with
      major tumorigenic signals by manipulating GPCR-mediated pathways. We also discuss
      current data regarding novel GPCR targets that may provide promising
      opportunities for drug discovery in cancer prevention and treatment.

PMID- 21193873
TI  - Radiolabeled oligosaccharides nanoprobes for infection imaging.
AB  - Breast milk oligosaccharides act as soluble receptors for different pathogens
      which protect the newborn child from infection. The differentiation between
      loosening of prosthesis due to infective pathology septic or otherwise aseptic
      plays an important role in the patient management. We have labeled hydroxypropyl
      beta-cyclodextrin, oligosaccharide derivative, with technetium-99m ((99m)Tc
      HPbetaCD). The quality control of (99m)Tc-HPbetaCD was done by ITLC and
      characterized by electron microscopy and (1)H-nuclear magnetic resonance. The
      route of excretion of (99m)Tc-HPbetaCD nanoparticulate radiopharmaceutical was
      assessed in rats. Nanoparticles (99m)Tc HPbetaCD were injected in human subjects
      with clinically confirmed infected knee joints. Docking studies were done for
      ligand - protein interaction. The (99m)Tc-HPbetaCD was stable with good
      radiochemical yield (>98%) at pH 4.0 and 6.5. For single patient dose, 0.5-1.0mg
      HPbetaCD quantity was sufficient. (99m)Tc HPbetaCD was observed to form
      nanoparticles of 60-180 MUm. The (1)H NMR studies revealed the binding of (99m)Tc
      at C-8/H-8 position of HPbetaCD. The excretion of (99m)Tc HPbetaCD showed renal
      route of excretion. Docking studies demonstrated the interaction between HPbetaCD
      and bacterial maltose binding protein (MBP). The differentiation between septic
      and aseptic loosening was also evident on single photon emission tomography
      (SPET). In conclusion, these data indicated that (99m)Tc HPbetaCD is a promising
      radiopharmaceutical and may serve as molecular nanoprobe for infection imaging.

PMID- 21193874
TI  - Studies on the development of 99mTc-labeled biphosphonate alginate beads.
AB  - The preparation of alginate-dextran pyrophosphate/biphosphonate loaded beads,
      were labeled with technetium-99m ((99m)Tc) and rhenium-188 ((188)Re). The
      radiolabelled phosphonic acid derivatives,are well-known bone imaging agents and
      have also been used for bone pain palliation treatment. The alginates have been
      used extensively as an excipient in drug products due to their thickening, gel
      forming and stabilizing behavior. The aim of this study was the preparation of
      alginate polymeric beads with and without dextran coating, to be used for imaging
      and possible treatment. We studied (99m)Tc-labelled biphosphonate alginates. We
      reported our results on the basis of size, swelling capacity and the coating
      material. The size effect of loading, decreases size and increases loading
      capacity of alginate beads. Pyrophosphate (PYP) loaded beads had 95% swelling,
      while ethylene diamine tetramethylene phosphonic acid (EDTMP) loaded beads had
      90% (swelling). However combination of both (PYP+EDTMP) loaded beads had 95%
      swelling. Sustained drug release study indicated different ratios of EDTMP, PYP
      and EDTMP+PYP loaded beads on different days. Total drug extracted from 30 g
      beads was 1365.45 MUg, 5352.86 MUg and 711.8 MUg, from EDTMP, PYP and EDTMP+PYP
      respectively during 15 days of studies. Binding with PYP and EDTMP was 98% and
      99% respectively. In conclusion, (chemical and physical characteristics of
      (99m)Tc-biphosphonate and other alginate beads that we have prepared suggest that
      the alginate beads could be used for diagnostic and therapeutic purposes.).

PMID- 21193875
TI  - Macro-aggregates (MAA) of albumin for lung imaging. Studies on better tissue to
      background ratio, on MAA stability and reuse after its first preparation.
AB  - The present study was designed to develop stable and economically competitive
      radioactive technetium-99m macro-aggregates of albumin ((99m)Tc-MAA) which could
      be used for imaging of lungs. Macro-aggregates were freshly prepared and labeled
      with (99m)Tc pertechnetate by following the standard protocol which included
      incubation of formulation at 80(o) C for 10 min. We studied 7 rats in every
      experiment. The rats were injected intravenously with (99m)Tc MAA and were
      sacrificed after 10 min to study its distribution in the lungs and other non
      target tissues using gamma ray spectrometer. This standard protocol was further
      experimented upon in order to achieve high target to non target ratio. Different
      formulations were prepared by incubating them at 80 degrees for different
      incubation times of 5, 10, 15, 20, 25 and 30 min. Formulation of MAA prepared by
      incubating at 80 degrees for 20 min labeled with (99m)Tc showed the highest
      target to non target ratio. Another group of rats that received the above
      formulation were sacrificed after two additional time intervals of 5 and 15 min.
      The target to non target ratio was high in animals sacrificed after 5 min of
      injecting them with (99m)Tc the MAA formulation prepared by heating at 80 degrees
      for 20 min as compared to animals sacrificed after 10 and 15 min. Formulations of
      MAA following storage at room temperatures which varied from 5(o)C to 18(o)C, for
      different time durations 1, 2 and 9 days were also evaluated for their ability to
      be reused after reheating and labeling with (99m)Tc. The formulation of MAA kept
      for 9 days showed the best target to non-target ratio. The present study suggests
      that MAA once prepared can be reused following labeling with (99m)Tc even after 9
      days of storage with better target to non target ratio as compared to storage
      timer period of 1 and 2 days.

PMID- 21193876
TI  - Does left ventricular diastolic function deteriorate earlier than left
      ventricular systolic function in anthracycline cardiotoxicity?
AB  - Cardiotoxicity is the most important complication in patients receiving
      anthracycline chemotherapy. We studied the left ventricular diastolic function
      (LVDF) and systolic function (LVSF) in these patients and assessed whether LVDF
      deteriorates earlier than LVSF. We prospectively studied 58 patients (mean age
      48.02 +/- 13.87; 32 female, 26 male) on anthracycline treatment, before
      chemotherapy (S0) and after cumulative doses of 139 +/- 12 mg/m(2) (S1) and 308
      +/- 14 mg/m(2) (S2). The LVSF was computed in terms of left ventricular ejection
      fraction (LVEF) from equilibrium radionuclide angiography (ERNA). The peak
      ejection rate (PER), peak filling rate (PFR), time to peak ejection rate (TPER),
      time to peak filling rate (TPFR), 1/3rd filling fraction and ratio of PFR and PER
      were calculated from ERNA and were also standardized using 150 baseline ERNA
      studies. Statistical analysis was done by repeated measures analysis of variance
      (ANOVA). We found significant decrease in LVEF (P<0.001) and PER (P<0.001)
      between the S1 and S2 studies and PFR (P<0.007) between the S0 and S1 studies. In
      conclusion in patients receiving anthracycline treatment, LVDF deteriorates
      earlier than left ventricular systolic function (LVSF).

PMID- 21193877
TI  - The role of radionuclide lymphoscintigraphy in chyluria.
AB  - The objective of this study was to study the characteristics of chyluria on
      radionuclide lymphoscintigraphy and evaluate the diagnostic value of radionuclide
      lymphoscintigraphy in chyluria. In this report radionuclide lymphoscintigraphy
      was performed in 41 cases of chyluria patients and the imaging results were
      retrospectively analyzed. Among 41 cases, 30 of them were caused by filariasis, 4
      cases were secondary chyluria from abdomen surgery and 7 cases were caused by
      lymphangitis. Sixteen cases were proved as bilateral chyluria and 25 cases as
      unilateral chyluria by cystoscopy. The most common pattern of chyluria in
      radionuclide lymphoscintigraphy is that kidney or pelvis was imaged in the early
      phase of dynamic acquisition. In conclusion, radionuclide lymphoscintigraphy is a
      useful noninvasive method for detecting the origin site of chyluria, and for
      providing reliable information to perform safe operation.

PMID- 21193878
TI  - A comparison and validation of blood-pool imaging and ECG-gated SPET myocardial
      perfusion imaging to assess left ventricular ejection fraction.
AB  - The aim of this study was to validate the accuracy of left ventricular ejection
      fraction (LVEF) obtained by quantitative gated single photon emission tomography
      (QGS) perfusion imaging in comparison with gated blood-pool imaging. Resting
      gated myocardial perfusion imaging was performed in 269 patients with suspected
      or known coronary artery disease, and followed by equilibrium nuclear cardiac
      blood-pool imaging in one week. The later was considered as the reference
      standard. The LVEF from both methods were analyzed. The LVEF were calculated with
      QGS using Cedars Cardiac Quantification software. We found that LVEF from QGS and
      blood-pool (Bp)-LVEF were highly correlated (r=0.819, <0.001). Taken into
      consideration that QGS-LVEF was significantly different from Bp-LVEF (mean +/-
      SD: 57.77% +/- 19.28% vs 54.23% +/- 15.41%, P<0.05), data were further analyzed
      by grouping participants based on end-systolic ventricular volume (ESV). QGS-LVEF
      was not significantly different from Bp-LVEF in the group where that ESV was
      larger than 15m, (mean +/- SD: 52.71% +/- 16.11% vs 51.83% +/- 15.33%, P>0.05),
      whereas when ESV was smaller than 15 mL, QGS-LVEF was significantly higher than
      Bp-LVEF (mean +/- SD: 80.53% +/- 7.01%vs 65.06% +/- 10.37%, P<0.05). Our findings
      demonstrate that when ESV values are larger than 15 mL, QGS- LVEF could replace
      Bp-LVEF. However, when ESV value is smaller than 15 mL, LVEF should be assessed
      in combination with blood-pool imaging.

PMID- 21193879
TI  - The additive value of transient left ventricular dilation using two-day
      dipyridamole 99mTc-MIBI SPET for screening coronary artery disease in patients
      with otherwise normal myocardial perfusion: a comparison between diabetic and non
      diabetic cases.
AB  - The prognostic value of transient ischemic dilation (TID) has been previously
      confirmed; however, its clinical significance for screening coronary artery
      disease (CAD) with balanced ischemia, as a cause of false negative myocardial
      perfusion imaging (MPI), is unclear. The goal of this study was to determine the
      additive diagnostic value of TID ratio for screening CAD in separate subgroups of
      diabetic and non-diabetics with normal perfusion. Eighty six patients with
      intermediate probability of CAD who had TID more than one in the presence of
      otherwise normal MPI using two-day technetium-99m methoxy isobutyl isonitrile
      ((99m)Tc-MIBI) single photon emission tomography (SPET) and dipyridamole stress
      (summed stress score<3 and left ventricular cavity<90 mL) were included in a
      prospective cohort study comprising two subgroups of diabetic and non- diabetic
      patients. An inclusive work-up with multiple noninvasive tests was performed for
      all patients from whom 38 cases subsequently underwent coronary angiography and
      48 cases were categorized in the group with a very low likelihood (<5%) of CAD on
      the basis of clinical and paraclinical data over a minimum of 18 months follow
      up. The TID ratio was calculated using automated software. Gensini score (GS) as
      an indicator of severity/extent of stenosis and coronary artery index (CAI) as
      the number of arteries with more than 50% narrowing were calculated based on
      angiographic findings. Our results showed that only in diabetic patients with
      three-vessel disease, TID ratio (1.47 +/- 0.23) differs significantly from the
      other groups of CAD. In diabetic patients subgroup, TID ratio correlated strongly
      with GS (r=0.957, P<0.0001) and CAI (r=0.659, P=0.001), while such correlations
      were not seen in the non-diabetic patients. On the basis of receiver operating
      characteristic curve analysis for screening CAD in diabetic patients with normal
      myocardial perfusion, 100% sensitivity and 77.8% normalcy rate were achieved when
      TID more than 1.16 was regarded as abnormal. No distinct cut-off value for
      abnormal TID was obtained in the non-diabetic patients. In conclusion, TID in
      diabetic patients without regional myocardial perfusion abnormality is an
      important sign of CAD especially when TID ratio exceeds 1.16. The higher TID
      ratio in these cases may predict increasing possibility of severe and extensive
      CAD. The value of TID in non-diabetic patients with otherwise normal MPI is not
      clearly determined.

PMID- 21193880
TI  - Is 0.75 mm Breslow thickness the correct cut-off point for performing sentinel
      node biopsy in patients with melanoma?
AB  - Currently, in patients with malignant melanoma there is no clear cut-off point of
      Breslow thickness in order to avoid unnecessary lymph node excision surgery,
      without missing metastatic nodes. We retrospectively studied a cohort of 64
      patients, with pathologically proven malignant melanoma, who underwent lymph node
      scintigraphy and surgical resection of the sentinel node, during the last two
      years. The patients were divided into 5 groups: Group 1: Ten patients, mean age
      46 +/- 6 years (range 40-55 years), with Breslow thickness of the lesion 0.51
      0.75 mm. Group 2: Eleven patients, mean age 41 +/- 9 years (range 31-61 years),
      with Breslow thickness 0.76-1mm. Group 3: Twelve patients, mean age 59 +/- 12 (41
      76 years), with Breslow thickness 1.01-1.25 mm. Group 4: Fourteen patients, mean
      age 61 +/- 8 (38-74 years), with Breslow thickness 1.26-1.5mm. Group 5: Seventeen
      patients, mean age 56 +/- 10 (32-71 years), with Breslow thickness >1.5mm. We
      found only seven infiltrated sentinel lymph nodes. From these, 3 patients
      belonged to the 5th group (Breslow>1.5mm), two patients to the 4th group (Breslow
      1.26-1.5mm), one patient in the 3rd group (Breslow 1.01-1.25 mm) and one patient
      to the 2nd group (Breslow 0.76-1mm). Since there was no positive sentinel lymph
      node in any patient with Breslow thickness less than < 0.75 mm, we conclude that
      sentinel lymph node biopsy in patients with Breslow thickness less than < 0.75 mm
      may not be useful and might not be carried out, except in high risk cases such as
      melanomas with ulceration, high mitotic rate and vertical growth phase.

PMID- 21193881
TI  - 65Zn kinetics as a biomarker of DMH induced colon carcinogenesis.
AB  - Dietary factors are considered crucial for the prevention of initiating events in
      the multistep progression of colon carcinoma. There is substantial evidence that
      zinc may play a pivotal role in host defense against several malignancies,
      including colon cancer. The present study was conducted to evaluate the kinetics
      of (65)Zn utilization following experimental colon carcinogenesis in rat model.
      Twenty rats were segregated into two groups viz., untreated control and
      dimethylhydrazine (DMH) treated. Colon carcinogenesis was established through
      weekly subcutaneous injections of DMH (30 mg/kg body weight) for 16 weeks. Whole
      body (65)Zn kinetics followed two compartment kinetics, with Tb(1) representing
      the initial fast component of the biological half-life and Tb(2), the slower
      component. The present study revealed a significant depression in the Tb(1) and
      Tb(2) components of (65)Zn in DMH treated rats. Further, DMH treatment caused a
      significant increase in the percent uptake values of (65)Zn in the colon, small
      intestine, kidney and blood, whereas a significant decrease was observed in the
      liver. Subcellular distribution revealed a significant increase in (65)Zn uptake
      in the mitochondrial and microsomal fractions following 16 weeks of DMH
      supplementation. In conclusion, the present study demonstrated a slow
      mobilization of (65)Zn during promotion of experimentally induced colon
      carcinogenesis and provides a physiological basis for the role of (65)Zn in colon
      tumorigenesis, which may have clinical implications in the management of colon
      cancer.

PMID- 21193882
TI  - Evaluation of bone mineral density in premature ovarian failure.
AB  - This study was performed to evaluate whether or not early menopause and premature
      ovarian failure can cause an increased risk of osteoporosis. The bone mineral
      density (BMD) of the 2nd and 4th lumbar spine as well as femoral neck in 29 cases
      with secondary amenorrhea were compared with a reference data using a dual-energy
      X-ray absorptiometry on a bone densitometer: Serum levels of luteinizing hormone,
      follicular stimulating hormone, calcium and phosphorus were also measured. Both
      in 20-29 years and in 30-39 years, BMD were significantly lower than their normal
      range as compared with a reference data from a large study of the same population
      (P value<0.05). At lumbar vertebrae, 2 cases had osteopenia and 17 had
      osteoporosis while at the femoral neck, 17 cases had osteopenia and 4
      osteoporosis. Only serum levels of phosphorus had positive relationship with
      femoral neck BMD (P value<0.05). It may be possible to decrease fracture
      incidence through the early diagnosis of individuals at risk by BMD. In
      conclusion, our study indicates that females with early onset of menopause and
      premature ovarian failure had lower value of BMD in both femoral neck and lumbar
      vertebrae implying the need for more bone health measures.

PMID- 21193883
TI  - The role of scintigraphy in the evaluation of brain malignancies.
AB  - The gold standard for diagnosis of primary brain tumors is histopathological
      evaluation of the obtained tissue samples. Nevertheless, anatomical and
      functional imaging modalities have a determinative role in the precise
      localization and characterization of these lesions. In this review we focus on
      the clinical applications and future potentials of nuclear medicine procedures.
      Several single photon emission tomography (SPET) tracers such as thallium-201
      chloride ((201)TlCl(2)), technetium-99m ((99m)Tc) methoxyisobutylisonitrile
      (MIBI), (99m)Tc-tetrofosmin (TF) and 3-[iodine-123] iodo-alpha- methyl-L-tyrosine
      ((123)I-IMT) have been utilized in the diagnosis of brain tumors. Positron
      emission tomography (PET) alone or fused with computed tomography (CT), are
      widely acceptable methods in oncology, at present and for the future.

PMID- 21193885
TI  - Pyomyositis mimicking osteomyelitis detected by SPET/CT.
AB  - Pyomyositis is a relatively infrequent, sub-acute primary bacterial muscle
      infection, which due to its non specific clinical findings is unlikely to be
      early diagnosed especially in diabetic patients. This diagnostic delay may be
      fatal. Therefore, early diagnosis and prompt treatment are imperative. We present
      a poorly-controlled diabetic patient who was referred to our Nuclear Medicine
      department for a bone scan to evaluate osteomyelitis. Routine three-phase-planar
      scintigraphy was falsely positive for osteomyelitis in the left fibula, however,
      single photon emission tomography (SPET/CT) images clearly showed abnormal uptake
      in the calf muscles rather than the bone with evidence of low-attenuation lesions
      in these muscles. SPET/CT and magnetic resonance imaging (MRI) provided essential
      information to the clinicians to consider other diagnoses rather than
      osteomyelitis. MRI showed inter and intra-muscular collections consistent with
      multiple abscesses. Based on medical history, SPET/CT and MRI findings, the
      diagnosis of pyomyositis was established. The patient underwent successfully
      multiple incision-drainage procedures with subsequent intravenous antibiotic
      treatment and was discharged after complete recovery. In conclusion we advocate
      the use of SPET/CT for the detection of pyomyositis.

PMID- 21193884
TI  - Multiple extraosseous accumulation of 99mTc-MDP in acute lymphocytic leukemia and
      reference to literature.
AB  - Technetium-extraosseous accumulation of technetium-99m-methyl diphosphonate
      ((99m)Tc-MDP) on bone scan is not usual. It was described and in various diseases
      with solitary spleen or lung uptake. Simultaneous splenic, pulmonary and renal
      concentration of (99m)Tc-MDP has not been illustrated previously. Herein, we
      present a 17 years old man with acute lymphocytic leukemia (ALL) in whom (99m)Tc
      MDP was accumulated in the spleen, both lungs and the kidneys. Related literature
      was mentioned.

PMID- 21193886
TI  - Potential role and implications of 18F-FDG-PET/CT imaging in the detection and
      management of iliopsoas abscess.

PMID- 21193887
TI  - Increased muscle 18F-FDG uptake in an agitated child.

PMID- 21193888
TI  - Follow-up 18F-FDG-PET for the detection of inguinal metastatic penile squamous
      cell carcinoma: an ultrasound guided fine-needle aspiration.

PMID- 21193889
TI  - Incremental diagnostic value of SPET/CT in precise localization of extraskeletal
      uptake of bone-seeking agents in multiple myeloma.

PMID- 21193890
TI  - Imaging with 18F-FDG PET/CT of a primitive primary neuroectodermal tumor of the
      chest wall, in an adult.

PMID- 21193891
TI  - 18F-FDG uptake in small bowel intussusception in a patient of Langerhans cell
      histiocytosis and its resolution following successful conservative medical
      management.

PMID- 21193892
TI  - Negative findings of regional cerebral blood flow with (99m)Tc-ethyl cysteinate
      dimmer in Susac's syndrome.

PMID- 21193893
TI  - Gated myocardial perfusion imaging of double-chambered left ventricle.

PMID- 21193894
TI  - A malconfigured urinary bladder on post renal transplant scintigraphy in a
      patient with Prune Belly syndrome.

PMID- 21193895
TI  - 99mTc-DTPA dynamic imaging of left retroperitoneal paraganglioma.

PMID- 21193896
TI  - 18F-FDG PET/CT in a rare case of diffuse large B cell lymphoma presenting as deep
      vein thrombosis with bilateral breast involvement and subcutaneous nodules.

PMID- 21193897
TI  - [Estimation of fetal dose during diagnostic nuclear medicine procedures
      especially in child bearing Greek women].
AB  - Medical uses of radiation have grown rapidly over the past decade in Hellas. A
      part of these may concern Diagnostic Nuclear Medicine procedures implemented in
      pregnant patients. The potential detriment from ionizing radiation to
      embryo/fetus is related to the fetal dose and the stage of pregnancy at which
      exposure occurs. The purpose of this review is to inform about the risk from
      radiation to the embryo/fetus, to provide a data base of fetal doses in early
      pregnancy for nuclear medicine procedures in Hellas which are determined by
      National and European protocols and laws and to suggest actions that should be
      considered in order to optimize the diagnostic procedure keeping the fetal dose
      as low as reasonably achievable maintaining a good diagnostic result for the
      pregnant. Average fetal dose for most nuclear medicine procedures in Hellas
      varies between 0,3 and 18 mGy doses which can not justify the termination of
      pregnancy.

PMID- 21193898
TI  - [Nuclear medicine applications of the gastrointestinal tract in pediatric
      surgery].
AB  - There are pathological entities of the gastrointestinal tract whose investigation
      and follow-up remain quite challenging for pediatric surgeons. Although there are
      many new diagnostic techniques, radionuclide applications still remain important.
      Nuclear medicine plays a crucial role in diagnosis of biliary atresia and
      contributes to its differential diagnosis from neonatal hepatitis with an
      accuracy of 95% through cholescintigraphy. This method also detects postoperative
      complications, such as bile leaks and obstruction after liver transplantation in
      children. Technetium-99m pertechnetate scan is considered the standard method for
      preoperative diagnosis of a Meckel's diverticulum, characterized by a specificity
      of 95% and a sensitivity of 85%. Milk scan is the most sensitive noninvasive
      method for detecting gastroesophageal reflux, due to its high temporal
      acquisition rate and reveals tracheoesophageal communications in neonates
      suffering from persistent cough and recurrent pulmonary infections. Finally, in
      case of necrotizing enterocolitis, Nuclear Medicine has to offer the measurement
      by radioimmunological methods of markers such as IL-6, T- antigen, I-FABP,
      glutathione S-transferase and beta-galactocidase of intestinal mucosa cells,
      which are useful in the diagnosis, follow-up and prognosis of the disease. In
      conclusion, radionuclide techniques in the investigation of the gastrointestinal
      tract in neonates and children are useful functional methods, with lower
      radiation exposure compared to radiological techniques that are usually applied.

PMID- 21193899
TI  - The oral histone deacetylase inhibitor ITF2357 reduces cytokines and protects
      islet beta cells in vivo and in vitro.
AB  - In type 1 diabetes, inflammatory and immunocompetent cells enter the islet and
      produce proinflammatory cytokines such as interleukin-1beta (IL-1beta), IL-12,
      tumor necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma); each
      contribute to beta-cell destruction, mediated in part by nitric oxide. Inhibitors
      of histone deacetylases (HDAC) are used commonly in humans but also possess
      antiinflammatory and cytokine-suppressing properties. Here we show that oral
      administration of the HDAC inhibitor ITF2357 to mice normalized streptozotocin
      (STZ)-induced hyperglycemia at the clinically relevant doses of 1.25-2.5 mg/kg.
      Serum nitrite levels returned to nondiabetic values, islet function improved and
      glucose clearance increased from 14% (STZ) to 50% (STZ + ITF2357). In vitro, at
      25 and 250 nmol/L, ITF2357 increased islet cell viability, enhanced insulin
      secretion, inhibited MIP-1alpha and MIP-2 release, reduced nitric oxide
      production and decreased apoptosis rates from 14.3% (vehicle) to 2.6% (ITF2357).
      Inducible nitric oxide synthase (iNOS) levels decreased in association with
      reduced islet-derived nitrite levels. In peritoneal macrophages and splenocytes,
      ITF2357 inhibited the production of nitrite, as well as that of TNFalpha and
      IFNgamma at an IC(50) of 25-50 nmol/L. In the insulin-producing INS cells
      challenged with the combination of IL-1beta plus IFNgamma, apoptosis was reduced
      by 50% (P < 0.01). Thus at clinically relevant doses, the orally active HDAC
      inhibitor ITF2357 favors beta-cell survival during inflammatory conditions.

PMID- 21193901
TI  - The patterns of population differentiation in a Brassica rapa core collection.
AB  - With the recent advances in high throughput profiling techniques the amount of
      genetic and phenotypic data available has increased dramatically. Although many
      genetic diversity studies combine morphological and genetic data, metabolite
      profiling has yet to be integrated into these studies. For our study we selected
      168 accessions representing the different morphotypes and geographic origins of
      Brassica rapa. Metabolite profiling was performed on all plants of this
      collection in the youngest expanded leaves, 5 weeks after transplanting and the
      same material was used for molecular marker profiling. During the same season a
      year later, 26 morphological characteristics were measured on plants that had
      been vernalized in the seedling stage. The number of groups and composition
      following a hierarchical clustering with molecular markers was highly correlated
      to the groups based on morphological traits (r = 0.420) and metabolic profiles (r
      = 0.476). To reveal the admixture levels in B. rapa, comparison with the results
      of the programme STRUCTURE was needed to obtain information on population
      substructure. To analyze 5546 metabolite (LC-MS) signals the groups identified
      with STRUCTURE were used for random forests classification. When comparing the
      random forests and STRUCTURE membership probabilities 86% of the accessions were
      allocated into the same subgroup. Our findings indicate that if extensive
      phenotypic data (metabolites) are available, classification based on this type of
      data is very comparable to genetic classification. These multivariate types of
      data and methodological approaches are valuable for the selection of accessions
      to study the genetics of selected traits and for genetic improvement programs,
      and additionally provide information on the evolution of the different
      morphotypes in B. rapa.

PMID- 21193900
TI  - Aging influences cardiac mitochondrial gene expression and cardiovascular
      function following hemorrhage injury.
AB  - Cardiac dysfunction and mortality associated with trauma and sepsis increase with
      age. Mitochondria play a critical role in the energy demand of cardiac muscles,
      and thereby on the function of the heart. Specific molecular pathways responsible
      for mitochondrial functional alterations after injury in relation to aging are
      largely unknown. To further investigate this, 6- and 22-month-old rats were
      subjected to trauma-hemorrhage (T-H) or sham operation and euthanized following
      resuscitation. Left ventricular tissue was profiled using our custom rodent
      mitochondrial gene chip (RoMitochip). Our experiments demonstrated a declined
      left ventricular performance and decreased alteration in mitochondrial gene
      expression with age following T-H and we have identified c-Myc, a pleotropic
      transcription factor, to be the most upregulated gene in 6- and 22-month-old rats
      after T-H. Following T-H, while 142 probe sets were altered significantly (39 up
      and 103 down) in 6-month-old rats, only 66 were altered (30 up and 36 down) in 22
      month-old rats; 36 probe sets (11 up and 25 down) showed the same trend in both
      groups. The expression of c-Myc and cardiac death promoting gene Bnip3 were
      increased, and Pgc1-alpha and Ppar-alpha a decreased following T-H. Eleven tRNA
      transcripts on mtDNA were upregulated following T-H in the aged animals, compared
      with the sham group. Our observations suggest a c-myc-regulated mitochondrial
      dysfunction following T-H injury and marked decrease in age-dependent changes in
      the transcriptional profile of mitochondrial genes following T-H, possibly
      indicating cellular senescence. To our knowledge, this is the first report on
      mitochondrial gene expression profile following T-H in relation to aging.

PMID- 21193902
TI  - Horizontal gene transfer amongst probiotic lactic acid bacteria and other
      intestinal microbiota: what are the possibilities? A review.
AB  - Probiotics are live cultures, usually lactic acid bacteria, which are ingested to
      promote a healthy gastrointestinal tract. These organisms require certain traits
      to survive and compete in this niche, but these traits may be transferred to
      other microbiota in the gastrointestinal tract (GIT). Similarly, virulence
      factors from pathogens may be acquired by probiotic strains. Bacteria have
      developed a plethora of methods to transfer genetic material between strains,
      species and genera. In this review, the possible factors that may be exchanged
      and the methods of exchange are discussed.

PMID- 21193903
TI  - Therapeutic effects of Clostridium botulinum C3 exoenzyme.
AB  - C3 exoenzyme from Clostridium botulinum, specifically ADP-ribosylates small GTP
      binding proteins RhoA, B, and C. ADP-ribosylation causes functional inactivation
      of Rho proteins resulting in cessation of the complete downstream signaling. Rho
      proteins are general regulators of a lot of essential cellular functions, among
      others, the neuronal growth cone. Rho activation, triggered by neuronal injury,
      inhibits neuronal repair mechanisms. To prevent the detrimental effect of active
      Rho in the recovery of injured neuronal systems, C3 has become a promising drug
      to inactivate RhoA in neurons. During the advancement of C3 to a drug candidate,
      it was found that ADP-ribosyltransferase activity of C3, in fact, is not
      essential for axonal and dendritic growth and branching. Rather, a peptide
      fragment of C3 covering the surface exposed ARTT loop from C3 (C3(154-182)
      peptide) is sufficient to induce growth and branching of neurons comparable to
      the effect of full-length C3. Whereas full-length C3 also acts on astrocytes and
      microglia to induce-at least in an in vitro model-inflammation and glial scar
      formation, C3(154-182) peptide is inert and seems only to act on neurons. In
      addition to its axono- and dendritotrophic effects on cultured primary
      hippocampal neurons, C3(154-182) peptide enhanced functional recovery and
      regeneration in a mouse model of spinal cord injury. Thus, in a proof-of
      principle experiment, C3 peptide was shown to be efficacious in post-traumatic
      neuro-regeneration.

PMID- 21193904
TI  - SPE/RP-HPLC using C1 columns: an environmentally friendly alternative to
      conventional reverse-phase separations for quantitation of beta-carboline
      alkaloids in human serum samples.
AB  - The analysis of beta-carboline alkaloids presents a renewed interest due to their
      biological relevance and their increasing popularity as recreational drugs. In
      the present work, a novel chromatographic reverse-phase high-performance liquid
      chromatography (RP-HPLC) method with fluorimetric detection has been applied to
      the determination of beta-carbolines spiked in human serum samples. The
      chromatographic procedure involves the use of less retentive, unusual C1 columns
      combined with hydro-alcoholic mobile phases and the use of beta-cyclodextrin or
      (2-hydroxypropyl)-beta-cyclodextrin as mobile-phase additives. The effective
      combination of C1 columns and the modified mobile phases with cyclodextrins leads
      to a considerable reduction in the organic proportion in the mobile phase (up to
      50%) with good resolution and efficiency. Besides, the presence of cyclodextrins
      allows the use of ethanol, a green solvent, as the organic component in the
      mobile phase. Traditional RP-HPLC thus becomes an attractive eco-separation
      technique using conventional stationary phases under simple and user-friendly
      experimental conditions. Solid-phase extraction was employed as sample clean-up
      protocol with attractive features, i.e., a low consumption of organic solvents,
      time and step economy and diminished need for sample handling. The analytical
      procedure was completely validated showing satisfactory figures of merit. Limits
      of detection of 10(-9)-10(-10) M can be achieved. The recoveries obtained for the
      total methodology (sample pre-treatment and chromatographic determination in the
      case of the mobile phases containing cyclodextrins) were very satisfactory (95
      107%) as well as the intraday (2-3%) and interday precision values (3-7%). The
      use of 3-hydroxymethyl-beta-carboline as an internal standard allows the
      comparison of the goodness of response of the analytical methodology in the
      presence or absence of cyclodextrins.

PMID- 21193905
TI  - Retrograde transureteral approach: a safe and efficient treatment for recurrent
      cystine renal stones.
AB  - Most patients presenting cystinuria require multiple urological procedures during
      their lifetime. In this kind of patients the availability of minimally invasive
      procedure represents an advantage of minimizing the cumulative morbidity of
      several repeated treatments. Herein we report our experience using
      ureterorenoscopy (URS) for the treatment of recurrent renal cystine stones. From
      2003 to 2007, 10 patients (4 males and 6 females) with one or multiple recurrent
      renal cystine stones underwent URS. Overall, 21 procedures have been performed.
      Mean maximum diameter of stones was 11.2 mm (range 5-30 mm). Either 8-9.5 F
      semirigid or 7.9 F flexible ureteroscopes were used. In 6 cases, stones were
      removed using a basket; in 9 procedures laser lithotripsy with flexible scope was
      performed; in 6 cases renal calculi were pulled down in the ureter using flexible
      instrument and then shattered with laser introduced by semirigid instrument.
      Stone-free status was defined as the absence of any residual fragment. A complete
      stone clearance was obtained in 15 out of 21 procedures (71%). In 5 cases (24%)
      significant residual fragments occurred; in the remaining case (5%) URS was
      ineffective. In 5 out of these unsuccessful procedures, stone clearance was
      obtained with auxiliary treatments. The last patient has not been treated yet. No
      major complications occurred as a result of the procedures. URS offers excellent
      advantages in case of recurrent hard calculi such as cystine stones. Minimally
      invasive procedures allow satisfactory outcomes, improving patients' quality of
      life.

PMID- 21193906
TI  - An alternative treatment for high-burden ureteral stones: percutaneous antegrade
      ureteroscopy.
AB  - The treatment of large proximal ureteral stones continues to be controversial. We
      evaluated the antegrade percutaneous approaches for the proximal ureteral stones
      in our clinic. In this study, 73 percutaneous antegrade ureteroscopy (PAU)
      operations applied to proximal ureteral stones between February 2005 and December
      2009 were included. The stones were located between ureteropelvic junction and
      4th lumbar vertebra. PAUs were applied through appropriate calyx with the
      patients in prone position. During operations, amplatz dilatators were used for
      dilatation, and pneumatic lithotripter was used for stone fragmentation. Patients
      were evaluated according to their success rate, complications, hospitalization
      period, and preference of drainage tube etc. Patients' mean age was 52.21 years,
      the mean stone diameter was 19.47 mm (range 15-25), the mean stone burden was
      283.76 +/- 49.12 mm(2) (mean +/- SD) (range 188.5-392.7) and the mean
      hospitalization time 1.69 days. Single access done in 68 patients and two
      accesses were needed in 5 patients. Sixty-eight patients (93.1%) became stone
      free. Nephrostomy tubes were placed in 12 patients after operation, while
      tubeless approach was preferred in 61 patients. Complications were seen in five
      patients. There were not any complications reported during the follow-up period.
      PAU is an effective and safe treatment modality if appropriate calyx access was
      performed. The possibility of renal stone treatment in the same session is an
      important advantage of this modality.

PMID- 21193907
TI  - A rare antenatally detected mass of the hand: tumour or congenital anomaly?
AB  - Tumour and tumour-like lesions of the hand can arise from various tissues and may
      present at birth. Rarely, anomalies of the hand may have an appearance mimicking
      a mass. We describe the imaging features of an antenatally detected floating
      thumb and describe its unusual mass-like appearance. While no hand tumour with
      similar imaging appearance has been reported, a few congenital lesions mimicking
      this appearance have been described. Awareness of these anomalies and
      identification of the typical imaging features of floating thumb allow diagnosis
      to be made with certainty.

PMID- 21193908
TI  - Isolated tear of the plantaris tendon: ultrasound and MRI appearance.
AB  - We report a retrospective analysis of the ultrasound and magnetic resonance
      imaging appearance of five patients with isolated plantaris tendon tears. Both
      imaging techniques allowed detection of the tear, assessment of its severity and
      of its location. Compared with magnetic resonance imaging, ultrasound resulted in
      a less expensive and time-consuming evaluation. Isolated plantaris tendon tears
      can clinically mimic Achilles tendon tears or thrombophlebitis. Unlike these
      conditions, plantaris tear has a benign outcome and does not need surgical
      treatment or anticoagulation.

PMID- 21193910
TI  - A novel approach to digital breast tomosynthesis for simultaneous acquisition of
      2D and 3D images.
AB  - OBJECTIVE: The complexity of anatomical structure within the breast represents
      the ultimate limit to signal detection on a mammogram. To increase lesion
      conspicuity Digital Breast Tomosynthesis (DBT) has been recently proposed and
      several manufacturers are currently performing clinical trials. In this study we
      investigate the potential of DBT with variable dose distribution by using a
      phantom in which details of interest are within a heterogeneous background.
      METHODS: To compare the performance of a commercial digital mammography unit and
      a DBT prototype, 2D and 3D images of the breast phantom were obtained at similar
      dose levels. RESULTS: As expected, DBT showed superior performance over digital
      mammography. Although certain details of interest are not detectable with digital
      mammography, DBT can reveal their signal by reducing the complexity of tissue
      structures. Additionally, the potential of the central projection in variable
      dose DBT is similar to the standard projection obtained with digital mammography.
      Finally, the uniform and variable dose approaches provided almost identical
      reconstructed slices. CONCLUSION: This preliminary investigation demonstrates
      that breast tomosynthesis acquired with variable dose distribution exhibits
      inherent 3D reconstruction advantages for structure noise removal and provides a
      2D projection with a physical image quality close to that of standard
      mammography.

PMID- 21193909
TI  - CD8 co-receptor promotes susceptibility of CD8+ T cells to transforming growth
      factor-beta (TGF-beta)-mediated suppression.
AB  - CD8+ T cell function depends on a finely orchestrated balance of
      activation/suppression signals. While the stimulatory role of the CD8 co-receptor
      and pleiotropic capabilities of TGF-beta have been studied individually, the
      influence of CD8 co-receptor on TGF-beta function in CD8+ T cells is unknown.
      Here, we show that while CD8 enhances T cell activation, it also enhances
      susceptibility to TGF-beta-mediated immune suppression. Using Jurkat cells
      expressing a full-length, truncated or no alphabetaCD8 molecule, we demonstrate
      that cells expressing full-length alphabetaCD8 were highly susceptible,
      alphabetaCD8-truncated cells were partially susceptible, and CD8-deficient cells
      were completely resistant to suppression by TGF-beta. Additionally, we determined
      that inhibition of Lck rendered mouse CD8+ T cells highly resistant to TGF-beta
      suppression. Resistance was not associated with TGF-beta receptor expression but
      did correlate with decreased Smad3 and increased Smad7 levels. These findings
      highlight a previously unrecognized third role for CD8 co-receptor which appears
      to prepare activated CD8+ T cells for response to TGF-beta. Based on the
      important role which TGF-beta-mediated suppression plays in tumor immunology,
      these findings unveil necessary considerations in formulation of CD8+ T cell
      related cancer immunotherapy strategies.

PMID- 21193911
TI  - Intraductally applied contrast-enhanced ultrasound (IA-CEUS) for evaluating
      obstructive disease and secretory dysfunction of the salivary glands.
AB  - Obstructive diseases of the salivary glands are a common problem, usually based
      on sialolithiasis, duct stenosis, foreign bodies or other more rare causes.
      Secretory dysfunction, often associated with Sjogren syndrome or post radiation
      treatment, is also a frequent problem. Several diagnostic tools exist to classify
      the disease; however conventional radiological imaging or ultrasound does not
      provide a diagnosis in 5-10% of all cases. Intraductally applied contrast
      enhanced ultrasound (IA-CEUS) improves the visualization of obstructive diseases
      of the salivary glands. IA-CEUS is a promising tool for assessing the ductal
      system and to diagnose and characterize abnormalities. This study describes the
      assessment of IA-CEUS in diagnosing different obstructive and chronic
      inflammatory conditions of the salivary glands.

PMID- 21193912
TI  - PSA density lower cutoff value as a tool to exclude pathologic upstaging in
      initially diagnosed unilateral prostate cancer: impact on hemiablative focal
      therapy.
AB  - PURPOSE: To investigate prostate-specific antigen density as a predictor for
      pathologic upstaging in patients initially thought to have unilateral prostate
      cancer. METHODS: We analyzed 438 patients with unilateral prostate cancer in
      prostate biopsy samples that were treated with radical prostatectomy. Bilateral
      or extracapsular growth in the final surgical specimens was defined as upstaging.
      Using Kaplan-Meier curves and a multivariate Cox proportional hazard model, we
      evaluated the oncologic effect of pathologic upstaging on biochemical recurrence
      free survival. Prostate-specific antigen density was evaluated as a diagnostic
      tool to predict upstaging using ROC-curve analysis. RESULTS: Of the patients,
      30.8% had bilateral prostate cancer or extracapsular extension in the surgical
      specimen. Prostate-specific antigen density was a diagnostic predictor for
      pathologic upstaging in patients initially thought to have unilateral prostate
      cancer (AUC 0.62, P < 0.001). Using a lower cutoff value of PSA density <0.056
      ng/ml/cm3, upstaging could be excluded in patients with a sensitivity of >98%.
      CONCLUSIONS: A considerable amount of patients that are initially diagnosed with
      unilateral prostate cancer on biopsy are underdiagnosed and are upstaged in the
      radical prostatectomy specimen. In general, AUC of PSA density is too low to use
      PSA density as diagnostic tool to predict pathologic upstaging in all patients.
      Nonetheless, PSA density could be used for hemiablative focal therapy decision
      making using a lower cutoff value of <0.056 ng/ml/cm3.

PMID- 21193913
TI  - Modulation of the rectoanal inhibitory reflex (RAIR): qualitative and
      quantitative evaluation in multiple sclerosis.
AB  - BACKGROUND: Rectoanal inhibitory reflex (RAIR) is a physiological modulated
      reflex involved in anorectal continence and defined by a relaxation of internal
      anal sphincter following rectal distension. Its existence depends on intramural
      autonomic ganglions and its modulation on the integrity of the autonomic nervous
      system (ANS). AIMS: The aim of this study was to analyse RAIR modulation in terms
      of amplitude and duration in multiple sclerosis (MS) patients. METHODS: Twenty
      one patients with MS and 40 control patients had anorectal manometry. Qualitative
      assessment (presence or absence) of RAIR was evaluated together with its
      modulation in amplitude and in duration. RESULTS: All patients had present RAIR
      for each volume of rectal distension (10-50 ml). Seven patients (33.3%) in the MS
      group had abnormal RAIR modulation in amplitude (odds ratio (OR) = 2.78, compared
      to control group, p = 0.11). Nine patients (42.9%) in the MS group had abnormal
      RAIR modulation in duration (p = 0.14, OR = 2.54, compared to control group).
      Alteration of RAIR modulation was not correlated with Expanded Disability Status
      Scale, faecal incontinence and constipation (p > 0.05). Course of MS (relapsing
      remitting MS or secondary progressive form) seems to be correlated to alteration
      of modulation in amplitude and in duration (OR = 1.31 and 1.07). CONCLUSION: Even
      if our results do not have the required statistical significance (p > 0.05), they
      are interesting. If RAIR is always present in MS, its modulation seems to be
      altered. A hypothesis for this lack of RAIR modulation could be the alteration of
      ANS, often involved in MS besides somatic nervous system lesions.

PMID- 21193914
TI  - Nonselective matrix metalloproteinase but not tumor necrosis factor-alpha
      inhibition effectively preserves the early critical colon anastomotic integrity.
AB  - BACKGROUND: Increased matrix metalloproteinase (MMP) activity has been implicated
      in the pathogenesis of colorectal anastomotic leakage. Tumor necrosis factor
      alpha (TNF-alpha) induces MMPs and may influence anastomosis repair. METHODS: We
      assessed the efficacies of the nonselective hydroxamate MMP inhibitor GM6001, the
      selective hydroxamate MMP inhibitor AG3340 and a TNF-alpha antagonist with
      respect to anastomotic breaking strength of left-sided colon anastomoses in male
      Sprague-Dawley rats. RESULTS: Systemic GM6001 treatment effectively blocked MMP
      activity and maintained the initial breaking strength day 0 of the anastomoses
      when administered subcutaneously as daily depositions (100 mg/kg) or continuously
      (10 mg/kg/day). In contrast, the anastomotic biomechanic strength was lowered by
      55% (p < 0.001) in vehicle-treated rats on postoperative day 3. GM6001 treatment
      increased breaking strength by 88% (p < 0.0005) compared with vehicle-treated
      rats day 3 and reduced (p = 0.003) the occurrence of spontaneous anastomotic
      dehiscence. Histologically, the anastomotic wound was narrower (p < 0.05) in the
      longitudinal direction in GM6001-treated animals whereas GM6001 had no
      significant effect on inflammatory cell infiltration or epithelialization. AG3340
      (10 mg/kg) increased (p < 0.012) breaking strength by 47% compared with vehicle
      on day 3 but did not significantly prevent the reduction of the initial breaking
      strength on day 0. Although the increased TNF-alpha levels in the wound were
      attenuated, the anastomotic breaking strength was not improved (p = 0.62) by the
      TNF-alpha (10 mg/kg) inhibitor given systemically. CONCLUSIONS: Pharmacological
      nonselective MMP inhibition ought to be explored as a prophylactic regimen to
      reduce anastomotic complications following colorectal resection. The involvement
      of TNF-alpha was insignificant in anastomotic wound healing in an experimental
      model.

PMID- 21193915
TI  - Assessment of left ventricular diastolic function in children after successful
      repair of aortic coarctation.
AB  - The purpose of the study was an assessment of left ventricular diastolic function
      in children after the successful repair of aortic coarctation (CoA). The
      prospective study concerned 32 pediatric patients after the CoA surgery. Tissue
      Doppler imaging parameters including strain and strain rate and the conventional
      echocardiographic indexes were analyzed in patients and healthy controls.
      Analysis of mitral annulus velocities, E-E' ratio, strain, and strain rate of
      left ventricular mid-cavity segments and conventional indexes of mitral inflow
      showed the worsening of left ventricular diastolic mechanics in the study group
      compared to healthy controls. The E/E' ratio was significantly higher in the
      study group compared to the control group (8.30 +/- 3.24 vs. 6.95 +/- 1.36; p <
      0.05). The early diastolic strain rate to late diastolic strain rate ratio as
      well as early to late diastolic strain ratio of the left ventricular mid-cavity
      segments were significantly lower in the study group compared to healthy controls
      (1.81 +/- 0.63 vs. 3.74 +/- 1.53; p < 0.001 and 1.20 +/- 0.49 vs. 3.41 +/- 1.26;
      p < 0.001). No differences of the pulmonary venous flow parameters between those
      two groups were observed. The left ventricular diastolic mechanics in
      hypertensive patients after CoA repair did not differ from normotensive subjects.
      Hypertensive and normotensive children after surgical repair of CoA are found to
      have worsening of the left ventricular diastolic mechanics suggesting the
      impairment of the active myocardial relaxation.

PMID- 21193916
TI  - Biomechanical comparison of three cemented stem removal techniques in revision
      hip surgery.
AB  - BACKGROUND: There are various techniques available to remove a cemented femoral
      component and distal cement in the case of septic or aseptic loosening,
      periprosthetic or component fracture. The present study describes the mechanical
      effects of three techniques: the transfemoral approach (TFA), the distal
      fenestration technique (DF) and the retrograde stem removal technique (RSR). An
      experiment on cadaveric femora was performed to establish if there are any
      differences in the resistance to fracture in and between the various groups.
      METHODS: Twenty-two paired femora were recovered from human cadavers and were
      frozen. These were later subdivided into three groups to provide similar
      specimens in each group (TFA, DF, RSR). The femora were tested using an Instron
      8874 biaxial testing system. The torque required to fracture was measured. Intra-
      and intergroup statistical analysis was performed. RESULTS: In the TFA group, the
      force required till fracture was significantly less than in controls. (p =
      0.018). Similar results were found in the DF group (p = 0.048). There was no
      difference in the RSR group (p = 1). Intergroup analysis showed the following:
      Femora in the TFA group required significantly less force to fracture than
      specimens in the DF group (p = 0.018) or the RSR group (p = 0.0055). Femora in
      the DF group required significantly less force to fracture than specimens in the
      RSR (p = 0.037). CONCLUSIONS: The TFA technique decreases the mechanical
      resistance of human cadaveric femora very significantly against rotational
      forces. The DF technique in the same setup also significantly decreases the
      resistance of bone, whilst no significant change is seen with the RSR technique.

PMID- 21193917
TI  - Destructive operations--a vanishing art in modern obstetrics: 25 year experience
      at a tertiary care center in India.
AB  - BACKGROUND: Destructive operations have a limited role in modern day obstetrics.
      In the developed countries, obstetrics has become so advanced that these
      instruments have actually been put away. However, in developing countries like
      India, these procedures have a limited role where obstructed labor still
      continues to plague thousands of women every year and accounts for 8% of maternal
      deaths. This study was planned to define the changing role of destructive
      operations in obstetrics over the years as more number of abdominal deliveries
      are conducted in modern day obstetrics than these procedures. MATERIALS AND
      METHODS: A retrospective analysis of destructive operations performed at the Post
      Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India,
      over a span of 25 years, between 1983 and 2007, was carried out. RESULTS: Of a
      total of 85,952 deliveries in PGIMER in these 25 years, there were 25,474
      cesarean deliveries (29.63%), and 8,826 (10.26%) operative vaginal deliveries.
      The total number of destructive operations performed was 230 (0.26%). There were
      202 craniotomies (87.8%), 13 decapitations (5.7%), 8 eviscerations (3.6%) and 7
      cleidotomies (2.9%). CONCLUSION: There should be an individualized approach to
      each case of obstructed labor. The health care provider has to decide on the
      options available to him to deliver the mother by the safest route without
      causing morbidity and mortality. If the fetus is dead, a destructive procedure
      can be considered in place of abdominal-route delivery which carries considerable
      risk to the debilitated mother in neglected labor.

PMID- 21193918
TI  - Primary precursor B cell lymphoblastic lymphoma of uterine corpus: case report
      and review of the literature.
AB  - INTRODUCTION: Primary lymphomas of the female genital tract are rare. Most
      involve the cervix rather than the uterine corpus. Many cases of primary
      endometrial lymphoma are diagnosed as diffuse large B cell type, whereas the
      precursor B cell lymphoblastic type is extremely rare. MATERIALS AND METHODS: We
      report a case of precursor B cell lymphoblastic lymphoma of uterine corpus which
      was successfully treated with surgery and chemotherapy. Staging evaluation
      revealed tumor limited to the uterine corpus (stage I(E)). After receiving a
      total abdominal hysterectomy, bilateral salpingooophorectomy, lymph node
      dissection and combination chemotherapy, the patient is currently free of disease
      after follow-up of 42 months. CONCLUSION: If correct diagnosis is established and
      appropriate therapy is chosen, the prognosis of precursor B-LBL of uterine corpus
      is expected to be good. The literature on primary precursor B cell lymphoblastic
      lymphoma of the uterine corpus is reviewed.

PMID- 21193919
TI  - Transcriptional activities of histone H3, cyclin D1 and claudin 7 encoding genes
      in laryngeal cancer.
AB  - Uncontrolled proliferation and a decrease in cell-cell adhesion are one of the
      most important characteristics of malignancy. Determination of replication
      dependent histone H3 can be applied as a proliferative marker. Cyclin D1 (CCND1)
      regulates the cell cycle by participating in the control of the G1/S phase
      transition. Claudins (CLDN) are components of tight junctions and may play an
      essential role in the loss of tissue cohesion. The aim of the study was to assess
      the mRNA expression of histone H3, cyclin D1, and claudin 7 genes in laryngeal
      squamous cell carcinoma (LSCC) and adjacent nonneoplastic tissues. The study
      group consisted of 32 patients with LSCC. Adjacent nonneoplastic tissues of
      incision lines were used as controls. Quantification of H3, CCND1 and CLDN7 mRNAs
      was performed by the use of real-time QRT-PCR assay. Molecular analysis showed a
      significantly higher expression of CCND1 (P = 0.0001; Wilcoxon test) and H3 (P =
      0.0141) genes in tumor tissues than in surrounding nonneoplastic tissues. On the
      contrary, transcriptional activity of claudin 7 gene was higher in histologically
      normal tissues; however, this difference was not statistically significant (P =
      0.1499). The data obtained indicate that laryngeal cancer is characterized by
      high proliferative potential mediated by increase in cyclin D1 and H3 mRNAs
      expression.

PMID- 21193921
TI  - Aseptic meningitis in a patient receiving treatment with anti-tumour necrosis
      factor alpha.

PMID- 21193920
TI  - The follow-up of patients with head and neck cancer: an analysis of 1,039
      patients.
AB  - In all cancer specialities, there has been much debate about the best follow-up
      regime. The provision of a service that meets high standards whilst being cost
      effective is increasingly pertinent. The objectives of the study were to examine:
      whether routine follow-up facilitates early diagnosis and recurrence; whether
      there is a cohort of patients who require a more intensive follow-up regime;
      whether follow-up should be customised to individual patients. A total of 1,039
      consecutive outpatient consultations were prospectively analysed in a multicentre
      study. All adult patients who had undergone multidisciplinary, multimodality
      management for head and neck cancer were included. The case mix was
      representative of all head and neck tumour sites and stages. Suspicion of
      recurrence was noted in 10% (n = 96/951) of patients seen routinely. This rose to
      68% (n = 60/88) for the subset of patients who had requested an appointment. Most
      recurrences were found within the first follow-up year (n = 64/156, 54%). Only
      0.3% (n = 3/1,039) of asymptomatic patients attending routine appointments were
      suspected of having a recurrence, and two (0.2%) were found to have an actual
      recurrence following investigation. Of the total number of patients reporting a
      new suspicious symptom, recurrence was suspected in 56% (n = 152/270). Patients
      thus had a 98.1% sensitivity to raising suspicion for a recurrence based on the
      reporting of new symptoms with a 99.6% negative predictive value. Our data show
      that the efficiency of the current follow-up regime at detecting suspected
      recurrence of head and neck cancer is low, suggesting the need for a customised,
      more focused follow-up regime, tailored to individual cases. Patient education
      and close relationships with clinicians and allied health-care professionals are
      essential for early diagnosis and management of cancer recurrence. Follow-up
      regimes within the first year should be most intensive as recurrence is most
      likely within this time, and it serves to alleviate patient anxiety in the early
      post-treatment period. More research needs to be carried out to investigate the
      role of patient self-reporting and surveillance of cancer recurrence.

PMID- 21193922
TI  - Taste function in patients with Parkinson disease.
AB  - Despite the important role of taste function in nutrition and health, little is
      known about changes in taste function caused by Parkinson disease (PD). The taste
      function of 31 PD patients and 29 healthy controls was assessed quantitatively
      using filter paper taste strip tests (TSTs) impregnated with four basic taste
      qualities at four different concentrations. The mean TST score was significantly
      lower in PD patients, as a consequence of taste impairment in the female PD
      patients (it did not differ significantly in males), which was likely to be
      attributable to the lower Mini-Mental State Examination score in patients with PD
      than in controls in women. TST scores in PD patients were not correlated with
      patient age, duration, or severity of their PD, or olfactory function. The
      findings of our study suggest that taste dysfunction should be included in the
      list of nonmotor symptoms of PD.

PMID- 21193923
TI  - Variation of NDRG2 and c-Myc expression in rat heart during the acute stage of
      ischemia/reperfusion injury.
AB  - N-Myc downstream regulated gene 2 (NDRG2), a Myc-repressed gene, is highly
      expressed in heart tissue. NDRG2 increases in response to hypoxia-induced stress
      and is involved in hypoxia-induced radioresistance. However, little is known
      about the expression changes and possible roles of NDRG2 in the heart under
      hypoxia condition. Here, the authors show that NDRG2, mainly localized in
      cardiomyocyte cytoplasm, was significantly reduced in myocardial tissue after
      acute ischemia/reperfusion (I/R) injury. Meanwhile, c-Myc was up-regulated
      following acute I/R injury, and the expression of c-Myc was significantly
      inversely correlated with that of NDRG2. In addition, overexpression of c-Myc in
      primary cultured cardiomyocyte repressed NDRG2 expression. Furthermore, the
      increase of cardiomyocyte apoptosis was correlated with the decrease of NDRG2
      protein during the acute phase of reperfusion. These data suggested for the first
      time that I/R injury-induced up-regulation of pro-apoptotic c-Myc expression may
      contribute to the down-regulation of anti-apoptotic NDRG2. This stress response
      might be involved in the novel mechanism of myocardial apoptosis induced by I/R
      injury in rat.

PMID- 21193924
TI  - The effects of 6-week-decoupled bi-pedal cycling on submaximal and high intensity
      performance in competitive cyclists and triathletes.
AB  - Aim of this work was to examine the effects of decoupled two-legged cycling on
      (1) submaximal and maximal oxygen uptake, (2) power output at 4 mmol L(-1) blood
      lactate concentration, (3) mean and peak power output during high intensity
      cycling (30 s sprint) and (4) isometric and dynamic force production of the knee
      extensor and flexor muscles. 18 highly trained male competitive male cyclists and
      triathletes (age 24 +/- 3 years; body height 179 +/- 11 cm; body mass 78 +/- 8
      kg; peak oxygen uptake 5,070 +/- 680 mL min(-1)) were equally randomized to
      exercise on a stationary cycle equipped either with decoupled or with traditional
      crank system. The intervention involved 1 h training sessions, 5 times per week
      for 6 weeks at a heart rate corresponding to 70% of VO(2peak). VO(2) at 100, 140,
      180, 220 and 260 and power output at 4 mmol L(-1) blood lactate were determined
      during an incremental test. VO(2peak) was recorded during a ramp protocol. Mean
      and peak power output were assessed during a 30 s cycle sprint. The maximal
      voluntary isometric strength of the quadriceps and biceps femoris muscles was
      obtained using a training machine equipped with a force sensor. No differences
      were observed between the groups for changes in any variable (P = 0.15-0.90;
      effect size = 0.00-0.30). Our results demonstrate that a 6 week (30 sessions)
      training block using decoupled crank systems does not result in changes in any
      physiological or performance variables in highly trained competitive cyclists.

PMID- 21193925
TI  - Postural ability reflects the athletic skill level of surfers.
AB  - This work analyses surfers' postural control and their use of visual information
      in static (stable) and dynamic (unstable) postures according to their level of
      competition. Two groups of healthy surfers were investigated: a group of local
      level surfers (LOC) (n = 8) and a group of national/international level surfers
      (NIN) (n = 9). Posture was assessed by measuring the centre of foot pressure with
      a force platform for 50 s with stable support and for 25 s with unstable support
      (sagittal or frontal plane). The tests were completed with the eyes open (the
      subjects looked at a fixed level target at a distance of 2 m) and closed (they
      kept their gaze in a straight-ahead direction). Results showed that the
      contribution of vision in postural maintenance, with unstable support was less
      important in the NIN surfers than in the LOC surfers and that the NIN surfers had
      better postural control than the LOC surfers. Firstly, the results suggest that
      expert surfers could shift the sensorimotor dominance from vision to
      proprioception for postural maintenance. Secondly, there is a relationship
      between the postural ability and the competition level of surfers. These
      observations are likely to induce new prospects of training for surfers.

PMID- 21193926
TI  - Melanoma histopathology report: proposal for a standardized terminology.

PMID- 21193928
TI  - Zoonotic linkage and variation in Cryptosporidium parvum from patients in the
      United Kingdom.
AB  - Relationships between patient exposure risks and variation within the
      Cryptosporidium parvum 60 kDa glycoprotein (GP60) gene were explored in samples
      isolated from human cases of cryptosporidiosis (n=69) in England and Wales. GP60
      family IIa predominated (n=56), followed by IId (n=9). One case was IIc, a newly
      named genotype IIcA5G3j, and isolates from three cases did not amplify with the
      GP60 primers. Cases with GP60 family IIa were more likely than IId to have
      visited a farm, or had contact with farm animals or with their faeces in the 2
      weeks prior to illness. Within GP60 family IIa, genotypes IIaA15G2R1 and
      IIaA17G1R1 predominated (22 cases each); nine other IIa genotypes accounted for
      12 cases. The IId genotypes were mainly IIdA17G1 and IIdA18G1 (3 each). Cases
      with IIaA17G1R1 were particularly linked to zoonotic exposures: visiting a farm
      or having farm animal contact in the 2 weeks prior to illness. These findings
      provide further evidence of zoonotic pathways for the transmission of C. parvum
      isolates.

PMID- 21193927
TI  - Clinical practice. Fibroblast growth factor (FGF)23: a new hormone.
AB  - Until a decade ago, two main hormones were recognized as directly affecting
      phosphate homeostasis and, with that, bone metabolism: parathyroid hormone and
      1,25(OH)(2) vitamin D (calcitriol). It was only a decade ago that the third major
      player hormone was found, linking gut, bone, and kidney. The physiologic role of
      fibrinogen growth factor (FGF)23 is to maintain serum phosphate concentration
      within a narrow range. Secreted from osteocytes, it modulates kidney handling of
      phosphate reabsorption and calcitriol production. Genetic and acquired
      abnormalities in FGF23 structure and metabolism cause conditions of either hyper
      FGF23-manifested by hypophosphatemia, low serum calcitriol, and
      rickets/osteomalacia-or hypo-FGF23, expressed by hyperphosphatemia, high serum
      calcitriol, and extra-skeletal calcifications. In patients with chronic renal
      failure, FGF23 levels increase as kidney functions deteriorate and are under
      investigation to learn if the hormone actually participates in the
      pathophysiology of the deranged bone and mineral metabolism typical for these
      patients and, if so, whether it might serve as a therapeutic target. This review
      addresses the physiology and pathophysiology of FGF23 and its clinical
      applications.

PMID- 21193929
TI  - The comparative morphology of Marshallagia marshalli and Ostertagia occidentalis
      (Nematoda: Strongylida, Trichostrongylidae) by scanning electron microscopy.
AB  - The systematics of the Ostertagiinae is unsettled with no agreement on how many
      genera and species are present in cattle and sheep. Ten species of Ostertagiinae
      are commonly parasitic in cattle and sheep. In the global fauna, six of 13
      ostertagiine genera are endemic to Iran. The life cycle of Ostertaginae is direct
      and ingested third-stage larvae after exsheatment in the rumen, penetrate the
      gastric glands in the abomasal mucosa where two parasitic moults occur before the
      L5 emerges from the gland. In the present work, Marshallagia marshalli and
      Ostertagia occidentalis, collected from the abomasums of sheep from Mashhad,
      Iran, is described. The association of light and scanning electron microscopy
      (SEM) allowed a detailed analysis of the morphology and ultrastructure of these
      nematodes. The male body length of M. marshalli and O. occidentalis were 9.3
      10.20 and 9.60-10.50 mm, respectively. The female body length of M. marshalli and
      O. occidentalis were 10.10-15.30 and 10.4-15.70 mm, respectively. One of cervical
      papillae is seen 333 and 250 MUm from the anterior end of male and female body
      surface in O. occidentalis and 287.5 and 200 MUm from the anterior end of male
      and female body surface in M. marshalli, respectively. The size of cervical
      papillae is 13.3 MUm in male and 10 MUm in female in O. occidentalis and 9.33 MUm
      in male and 8.57 MUm in female in M. marshalli. Some other taxonomic features of
      M. marshalli and O. occidentalis, such as details of cephalic region, the system
      of longitudinal and surface cuticular ridges (synlophe), the orientation of rays
      of the copulatory bursa, localization of vulva, morphology of vulvar flap, and
      posterior end of females are also documented by SEM.

PMID- 21193930
TI  - Characterization of the ZBTB42 gene in humans and mice.
AB  - A 12 kb haplotype upstream of the key signaling protein gene, AKT1, has been
      associated with insulin resistance and metabolic syndrome (Devaney et al. 2010).
      The region contains the first exon and promoter sequences of AKT1, but also
      includes the complete transcript unit for a highly conserved yet uncharacterized
      zinc finger-containing protein (ZBTB42). One of the component SNPs of the 12 kb
      haplotype metabolic syndrome haplotype changes a conserved amino acid in the
      predicted ZBTB42 protein, increasing the potential significance of the ZBTB42
      transcript unit for contributing to disease risk. Using RT-PCR of human and mouse
      cells, we verified that the two exon ZBTB42 was expressed and correctly spliced
      in human skeletal muscle, and murine C2C12 cells. Production of peptide
      antibodies showed the expected protein in human (47 kD) and mouse (49 kD)
      immunoblots, and murine tissue distribution showed strongest expression in muscle
      and ovary. Immunostaining showed nuclear localization of the ZBTB42 protein in
      human muscle. Confocal imaging analyses of murine muscle showed ZBTB42
      distributed in the nucleoplasm, with particular enrichment in nuclei underlying
      the neuromuscular junctions. The genetic association data of metabolic syndrome,
      coupled with the molecular characterization of the ZBTB42 transcript unit and
      encoded protein presented here, suggests that ZBTB42 may be involved in metabolic
      syndrome phenotypes.

PMID- 21193931
TI  - Heat shock proteins in chronic kidney disease.
AB  - Heat shock proteins (HSP) form a heterogenous, evolutionarily conserved group of
      molecules with high sequence homology. They mainly act as intracellular
      chaperones, protecting the protein structure and folding under stress conditions.
      The extracellular HSP, released in the course of damage or necrosis, play a
      pivotal role in the innate and adaptive immune responses. They also take part in
      many pathological processes. The aim of this review is to update the recent
      developments in the field of HSP in chronic kidney disease (CKD), in regard to
      three different aspects. The first is the assessment of the role of HSP, either
      positive or deleterious, in the pathogenesis of CKD and the possibilities to
      influence its progression. The second is the impact of dialysis, being a
      potentially modifiable stressor, on HSP and the attempt to assess the value of
      these proteins as the biocompatibility markers. The last area is that of kidney
      transplantation and the potential role of HSP in the induction of the immune
      tolerance in kidney recipients.

PMID- 21193932
TI  - A modified Delphi approach to standardize low back pain recurrence terminology.
AB  - Lack of standardization of terminology in low back pain (LBP) research has
      significantly impeded progress in this area. The diversity in existing
      definitions for a 'recurrence of an episode of LBP' and 'recurrent LBP' is an
      important example. The variety of definitions used by researchers working in this
      area has prevented comparison of results between trials and made meta-analyses of
      this data unfeasible. The aim of this study was to use a modified Delphi approach
      to gain consensus on definitions for a 'recurrence of an episode of LBP' (e.g.
      outcome event) and for 'recurrent LBP' (e.g. patient population). Existing
      definitions for both constructs were classified into the main features comprising
      the definition (e.g. 'duration of pain') and the items that defined each feature
      (e.g. 'pain lasting at least 24 h'). In each round, participants were asked to
      rate the importance of each feature to a definition of a 'recurrence of an
      episode of LBP', and a definition of 'recurrent LBP' and rank the items (defining
      each feature) in order of decreasing importance. Forty-six experts in LBP
      research, from nine different countries, participated in this study. Four rounds
      were completed with responses rates of 94, 91, 83, and 97% in rounds 1, 2, 3, and
      4, respectively. Consensus definitions were reached in both areas with 95% of
      panel members supporting the definition of a 'recurrence of an episode of LBP'
      and 92% of panel members supporting the definition of 'recurrent LBP'. Future
      research is necessary to evaluate these definitions.

PMID- 21193933
TI  - Cauda equina syndrome: a review of the current clinical and medico-legal
      position.
AB  - Cauda equina syndrome (CES) is a rare condition with a disproportionately high
      medico-legal profile. It occurs most frequently following a large central lumbar
      disc herniation, prolapse or sequestration. Review of the literature indicates
      that around 50-70% of patients have urinary retention (CES-R) on presentation
      with 30-50% having an incomplete syndrome (CES-I). The latter group, especially
      if the history is less than a few days, usually requires emergency MRI to confirm
      the diagnosis followed by prompt decompression by a suitably experienced surgeon.
      Every effort should be made to avoid CES-I with its more favourable prognosis
      becoming CES-R while under medical supervision either before or after admission
      to hospital. The degree of urgency of early surgery in CES-R is still not in
      clear focus but it cannot be doubted that earliest decompression removes the
      mechanical and perhaps chemical factors which are the causes of progressive
      neurological damage. A full explanation and consent procedure prior to surgery is
      essential in order to reduce the likelihood of misunderstanding and litigation in
      the event of a persistent neurological deficit.

PMID- 21193934
TI  - A modified "far-lateral" approach for safe resection of retroodontoid dural
      cysts.
AB  - Cystic mass lesions at the ventral craniocervical junction have been described
      only rarely in the past, however, they have received more attention with improved
      imaging modalities in recent years. These lesions have been approached by various
      operative procedures. A modified "far-lateral" approach combined with a C1
      hemilaminectomy without fusion was used to safely remove the cyst and decompress
      the cervical medulla in a 72-year-old woman with cervicooccipital pain and
      paresthesia in both arms. Following surgery, complete resolution of symptoms was
      achieved, and no recurrence at 1 year follow-up was detected. A modified "far
      lateral" approach offers several advantages when compared with other operation
      techniques.

PMID- 21193935
TI  - Use of twist-drill craniostomy with drain in evacuation of chronic subdural
      hematomas: independent predictors of recurrence.
AB  - BACKGROUND: Recurrence rates after chronic subdural hematoma (CSDH) evacuation
      with any of actual techniques [twist-drill craniostomy (TDC), burr-hole
      craniostomy, craniotomy] range from 5% to 30%. Use of drain has improved
      recurrence rates when used with burr-hole craniostomy. Now, we analyze predictors
      of recurrence of TDC with drain. METHOD: Three hundred twelve consecutive
      patients with CSDH have been studied in a retrospective study. Operative
      technique in all patients consisted in TDC with drain. Data recorded included any
      associated comorbidity. Radiologic measures of the CSDH before and after the
      procedure were studied. Clinical evaluation included Modified Rankin Scale,
      Glasgow Coma Scale (GCS), and neurological deficits. Two groups were compared:
      recurrence group and nonrecurrence group. Follow-up was for at least 1 year.
      RESULTS: Twelve percent experienced recurrence. Preoperative CSDH width,
      preoperative midline shift, postoperative midline width, postoperative CSDH
      width, and residual CSDH 1 month later were significantly associated with CSDH
      recurrence. The logistic regression model for the multivariate analysis revealed
      that postoperative midline shift and postoperative neurological deficit were
      significantly associated with CSDH recurrence. The duration of treatment with
      dexamethasone was found not to be related with recurrence. Mortality before
      hospital discharge was 1%. Hospital stay was 2.5 days. CONCLUSIONS: TDC with
      drain has similar results in recurrence rates, morbidity, mortality, and outcome
      as other techniques as burr-hole craniostomy with drain. Preoperative and
      postoperative hematoma width and midline shift are independent predictors of
      recurrence. Brain re-expansion and time of drain maintenance are important
      factors related with recurrence of CSDH. Future CSDH reservoirs must avoid
      negative pressure and sudden pressure changes inside the whole closed drain
      system.

PMID- 21193936
TI  - Membrane permeabilization of the African horse sickness virus VP5 protein is
      mediated by two N-terminal amphipathic alpha-helices.
AB  - The VP5 outer capsid protein of African horse sickness virus (AHSV) is cytotoxic
      when expressed in Spodoptera frugiperda (Sf-9) cells. Secondary structure
      analysis of the VP5 amino acid sequence of AHSV-9 identified two N-terminal
      amphipathic alpha-helices within the first 43 amino acids. Baculovirus expression
      of N- and C-terminal truncated VP5 proteins in Sf-9 cells indicated that the N
      terminal 43 amino acids correlated with low levels of protein expression and with
      increased membrane permeabilization and cytotoxicity. Exogenous addition of
      chemically synthesized VP5 peptides indicated that both N-terminal amphipathic
      alpha-helices are required for membrane permeabilization of Sf-9 cells. These
      findings suggest that AHSV VP5 is a membrane-destabilizing protein.

PMID- 21193937
TI  - Genetic diversity in curtoviruses: a highly divergent strain of Beet mild curly
      top virus associated with an outbreak of curly top disease in pepper in Mexico.
AB  - A full-length curtovirus genome was PCR-amplified and cloned from peppers in
      Mexico with symptoms of curly top disease. The cloned DNA of this isolate, MX
      P24, replicated in Nicotiana tabacum protoplasts and was infectious in N.
      benthamiana plants. Sequence analysis revealed that the MX-P24 isolate had a
      typical curtovirus genome organization and was most similar to beet mild curly
      top virus (BMCTV). However, sequence identities were at the threshold value for
      establishment of a new curtovirus species. To further investigate the biological
      properties of MX-P24, an agroinoculation system was generated. Agroinoculated
      shepherd's purse plants developed typical curly top symptoms, and virus from
      these plants was transmissible by the beet leafhopper (Circulifer tenellus). The
      host range of MX-P24 was similar to that of BMCTV, with curly top symptoms
      induced in common bean, pepper, pumpkin, shepherd's purse and tomato plants and
      mild or no symptoms induced in sugar beet plants. Together, these results
      indicate that MX-P24 is a highly divergent strain of BMCTV associated with an
      outbreak of curly top disease in peppers in Mexico.

PMID- 21193938
TI  - The influence of secondary interactions on complex stability and double proton
      transfer reaction in 2-[1H]-pyridone/2-hydroxypyridine dimers.
AB  - The 2-[1H]-pyridone/2-hydroxypyridine tautomeric pair and its 6-substituted
      complexes have been studied with the use of DFT(M05) method. The intermolecular
      interaction energy has been calculated and discussed in the light of secondary
      interaction concept. The attractive secondary interactions of O/NH and O/OH type
      and OH/NH and OH/OH repulsions have been analyzed in terms of stabilizing or
      destabilizing influence on intermolecular behavior. The transition states of the
      double proton transfer reaction have been found and the energy of activation has
      been determined. The activation energy of the proton transfer reaction, geometry
      of the complexes and transition states show NH(2) and/or OH groups influence the
      properties of complexes and transition states. The HOMA index of aromaticity was
      applied to describe the pi-electron delocalization in the heterocyclic rings.

PMID- 21193939
TI  - Topological description of the bond-breaking and bond-forming processes of the
      alkene protonation reaction in zeolite chemistry: an AIM study.
AB  - Density functional theory and atoms in molecules theory were used to study bond
      breakage and bond formation in the trans-2-butene protonation reaction in an
      acidic zeolitic cluster. The progress of this reaction along the intrinsic
      reaction coordinate, in terms of several topological properties of relevant bond
      critical points and atomic properties of the key atoms involved in these
      concerted mechanisms, were analyzed in depth. At B3LYP/6-31++G(d,p)//B3LYP/6
      31G(d,p) level, the results explained the electron density redistributions
      associated with the progressive bond breakage and bond formation of the reaction
      under study, as well as the profiles of the electronic flow between the different
      atomic basins involved in these electron reorganization processes. In addition,
      we found a useful set of topological indicators that are useful to show what is
      happening in each bond/atom involved in the reaction site as the reaction
      progresses.

PMID- 21193940
TI  - The role of hydrogen bonds in an aqueous solution of acetylsalicylic acid: a
      molecular dynamics simulation study.
AB  - This work focuses on the role of the dynamic hydrogen bonds (HB) formed in an
      aqueous solution of aspirin using molecular dynamics simulation. The statistics
      reveal the existence of internal HB that inhibit the rotational movements of the
      acetyl and the carboxylic acid groups, forcing the molecule to adopt a closed
      conformer structure in water, and playing an important role in stabilizing this
      conformation.

PMID- 21193941
TI  - Prediction of zanamivir efficiency over the possible 2009 influenza A (H1N1)
      mutants by multiple molecular dynamics simulations and free energy calculations.
AB  - As one of the most important antiviral drugs against 2009 influenza A (H1N1),
      will zanamivir be effective for the possible drug resistant mutants? To answer
      this question, we combined multiple molecular dynamics simulations and molecular
      mechanics generalized Born surface area (MM-GBSA) calculations to study the
      efficiency of zanamivir over the most frequent drug-resistant strains of
      neuraminidase including R293K, R152K, E119A/D and H275Y mutants. The calculated
      results indicate that the modeled mutants of the 2009-H1N1 strains except H275Y
      will be significantly resistant to zanamivir. The resistance to zanamivir is
      mainly caused by the loss of polar interactions. The identified potential
      resistance sites in this study will be useful for the development of new
      effective anti-influenza drugs and to avoid the occurrence of the state without
      effective drugs to new mutant influenza strains.

PMID- 21193942
TI  - Quantum chemical studies on the aminopolynitropyrazoles.
AB  - We have explored the geometric and electronic structures, band gap, thermodynamic
      properties, density, detonation velocity and detonation pressure of
      aminopolynitropyrazoles using the density functional theory (DFT) at the
      B3LYP/aug-cc-pVDZ level. The calculated detonation velocity and detonation
      pressure, stability and sensitivity of model compounds appear to be promising
      compared to the known explosives 3,4-dinitro-1 H-pyrazole (3,4-DNP), 3,5-dinitro
      1 H-pyrazole (3,5-DNP), hexahydro-1,3,5-trinitro-1,3,5-triazinane (RDX) and
      octahydro-1,3,5,7-tetranitro-l,3,5,7-tetraazocane (HMX). The position of NH(2)
      group in the polynitropyrazoles presumably determines the structure, stability,
      sensitivity, density, detonation velocity and detonation pressure.

PMID- 21193943
TI  - Inheritance of Charcot-Marie-Tooth disease 1A with rare nonrecurrent genomic
      rearrangement.
AB  - Rare copy number variations by the nonrecurrent rearrangements involving PMP22
      have been recently suggested to be associated with CMT1A peripheral neuropathy.
      As a mechanism of the nonrecurrent rearrangement, replication-based fork stalling
      template switching (FoSTeS) by microhomology-mediated break-induced replication
      (MMBIR) has been proposed. We found three Korean CMT1A families with putative
      nonrecurrent duplication. The duplications were identified by microsatellite
      typing and applying a CGH microarray. The breakpoint sequences in two families
      suggested an Alu-Alu-mediated rearrangement with the FoSTeS by the MMBIR, and a
      two-step rearrangement of the replication-based FoSTeS/MMBIR and meiosis-based
      recombination. The two-step mechanism has still not been reported. Segregation
      analysis of 17p12 microsatellite markers and breakpoint junction analysis
      suggested that the nonrecurrent rearrangements are stably inherited without
      alteration of junction sequence; however, they may allow some alteration of the
      genomic contents in duplication across generations by recombination event. It
      might be the first study on the pedigree analysis of the large CMT1A families
      with nonrecurrent rearrangements. It seems that the exact mechanism of the
      nonrecurrent rearrangements in the CMT1A may have a far more complex process than
      has been expected.

PMID- 21193944
TI  - Comparison of cardioprotective and anti-inflammatory effects of ischemia pre- and
      postconditioning in rats with myocardial ischemia-reperfusion injury.
AB  - OBJECTIVE: To compare cardioprotective and anti-inflammatory effects of ischemia
      preconditioning (IPC) and ischemia postconditioning (IPOC) in a rat myocardial
      ischemia-reperfusion injury (IRI) model. METHODS: Forty Sprague-Dawley rats were
      randomly divided equally into four groups. In the groups other than the sham
      group, the left anterior descending coronary artery was ligated for 30 min
      followed by a 180 min reperfusion in vivo. The control group was subjected to no
      additional intervention, the IPC group to three cycles of 5 min ischemia
      separated by 5 min reperfusion before the index ischemia and the IPOC group to
      three cycles of 10 s ischemia separated by 10 s reperfusion immediately after the
      end of the index ischemia. Hemodynamic changes during the ischemia and
      reperfusion were recorded. At 180 min of reperfusion, serum concentrations of
      troponin I (TnI), tumor necrosis factor alpha (TNF-alpha) and high-mobility group
      box 1 (HMGB-1) were assayed, and the infarction size was assessed by Evans blue
      and triphenyltetrazolium chloride staining. RESULTS: Compared to the control
      group, infarct size and serum concentrations of TnI, TNF-alpha and HMGB1 at 180
      min of reperfusion were significantly reduced in the IPC and IPOC groups.
      However, infarct size and serum concentrations of TNF-alpha and HMGB1 at 180 min
      of reperfusion were significantly increased in the IPOC group compared to the IPC
      group. CONCLUSIONS: In the rats with myocardial IRI in vivo, both IPC and IPOC
      can produce significant cardioprotective and anti-inflammatory effects. However,
      cardioprotective and anti-inflammatory effects provided by IPOC are weaker than
      with IPC.

PMID- 21193945
TI  - OLIG2 is differentially expressed in pediatric astrocytic and in ependymal
      neoplasms.
AB  - The bHLH transcription factor, OLIG2, is universally expressed in adult human
      gliomas and, as a major factor in the development of oligodendrocytes, is
      expressed at the highest levels in low-grade oligodendroglial tumors. In
      addition, it is functionally required for the formation of high-grade
      astrocytomas in a genetically relevant murine model. The pediatric gliomas have
      genomic profiles that are different from the corresponding adult tumors and
      accordingly, the expression of OLIG2 in non-oligodendroglial pediatric gliomas is
      not well documented within specific tumor types. In the current study, the
      pattern of OLIG2 expression in a spectrum of 90 non-oligodendroglial pediatric
      gliomas varied from very low levels in the ependymomas (cellular and tanycytic)
      to high levels in pilocytic astrocytoma, and in the diffuse-type astrocytic
      tumors (WHO grades II-IV). With dual-labeling, glioblastoma had the highest
      percentage of OLIG2 expressing cells that were also Ki-67 positive (mean = 16.3%)
      whereas pilocytic astrocytoma WHO grade I and astrocytoma WHO grade II had the
      lowest (0.9 and 1%, respectively); most of the Ki-67 positive cells in the
      diffuse-type astrocytomas (WHO grade II-III) were also OLIG2 positive (92-94%).
      In contrast to the various types of pediatric astrocytic tumors, all ependymomas
      WHO grade II, regardless of site of origin, showed at most minimal OLIG2
      expression, suggesting that OLIG2 function in pediatric gliomas is cell lineage
      dependent.

PMID- 21193946
TI  - Evaluation of venous thromboembolism risk following hospitalization.
AB  - A better understanding of the relationship between outpatient venous
      thromboembolism (VTE) and prior hospitalization is needed including data
      regarding the utilization of inpatient pharmacologic VTE prophylaxis and its
      effect on outpatient venous thromboembolic risk. The primary objective was to
      assess the association between development of outpatient VTE and inpatient
      hospitalization within the previous 90 days. Additional outcome measures included
      describing patients who received pharmacologic anticoagulation during
      hospitalization and identification of factors independently associated with VTE.
      Case patients in this matched case-control study were diagnosed with an
      outpatient deep vein thrombosis or pulmonary embolus between January 2005 and
      December 2007 and were matched on age with up to five to patients who were seen
      for an outpatient health maintenance visit but had no VTE during the same time
      frame as their matched case. Information collected from electronic administrative
      databases and patient medical records included health services utilization,
      medication use, medical diagnoses, and patient demographic information. Of 2190
      cases, 560 patients (25.6%) compared to 151 (1.4%) of 10,942 control patients
      were hospitalized in the previous 90 days (P < 0.001). Among hospitalized
      patients, 53.5% of cases and 47.0% of controls received an anticoagulant during
      hospitalization (P = 0.186). Factors associated with a VTE diagnosis included
      hospitalization for a surgical, medical, or orthopedic indication in the previous
      90 days, younger age, longer hospitalization, cancer and an elevated Chronic
      Disease Score. CONCLUSIONS: A strong association exists between outpatient VTE
      diagnosis and hospitalization and gaps in pharmacologic prophylaxis utilization
      during hospitalization are evident.

PMID- 21193947
TI  - Visual spectinomycin resistance (aadA(au)) gene for facile identification of
      transplastomic sectors in tobacco leaves.
AB  - Identification of a genetically stable Nicotiana tabacum (tobacco) plant with a
      uniform population of transformed plastid genomes (ptDNA) takes two cycles of
      plant regeneration from chimeric leaves and analysis of multiple shoots by
      Southern probing in each cycle. Visual detection of transgenic sectors
      facilitates identification of transformed shoots in the greenhouse, complementing
      repeated cycles of blind purification in culture. In addition, it provides a tool
      to monitor the maintenance of transplastomic state. Our current visual marker
      system requires two genes: the aurea bar (bar(au)) gene that confers a golden
      leaf phenotype and a spectinomycin resistance (aadA) gene that is necessary for
      the introduction of the bar(au) gene in the plastid genome. We developed a novel
      aadA gene that fulfills both functions: it is a conventional selectable aadA gene
      in culture, and allows detection of transplastomic sectors in the greenhouse by
      leaf color. Common causes of pigment deficiency in leaves are mutations in
      photosynthetic genes, which affect chlorophyll accumulation. We use a different
      approach to achieve pigment deficiency: post-transcriptional interference with
      the expression of the clpP1 plastid gene by aurea aadA(au) transgene. This
      interference produces plants with reduced growth and a distinct color, but
      maintains a wild-type gene set and the capacity for photosynthesis. Importantly,
      when the aurea gene is removed, green pigmentation and normal growth rate are
      restored. Because the aurea plants are viable, the new aadA(au) genes are useful
      to query rare events in large populations and for in planta manipulation of the
      plastid genome.

PMID- 21193949
TI  - Reduced expression of netrin-1 is associated with fetal growth restriction.
AB  - The objective of this study was to investigate the expression of netrin-1 in
      placenta from patients with fetal growth restriction (FGR) and its effect on the
      viability and apoptosis of human placental microvascular endothelial cells.
      Thirty-three patients with FGR (including eighteen severe cases) and twenty-four
      normal late pregnant women were investigated. The expression of netrin-1 in
      placental tissues was detected by employing immunohistochemistry, real-time PCR,
      and Western blotting. Human placental microvascular endothelial cells were
      isolated and, after treatment with netrin-1, examined for their viability and
      apoptosis by using MTT assay and flow cytometry. We demonstrated that the netrin
      1 was present in placenta. Netrin-1 was significantly reduced in pregnant women
      with FGR as compared with the controls. Furthermore, netrin-1 enhanced the
      viability of human placental microvascular endothelial cells and inhibited their
      apoptosis. Netrin-1 may regulate the development of placental vessels and plays a
      key role in the pathogenesis of FGR.

PMID- 21193948
TI  - Schisandrin B elicits a glutathione antioxidant response and protects against
      apoptosis via the redox-sensitive ERK/Nrf2 pathway in H9c2 cells.
AB  - This study investigated the signal transduction pathway involved in the
      cytoprotective action of (-)schisandrin B [(-)Sch B, a stereoisomer of Sch B].
      Using H9c2 cells, the authors examined the effects of (-)Sch B on MAPK and Nrf2
      activation, as well as the subsequent eliciting of glutathione response and
      protection against apoptosis. Pharmacological tools, such as cytochrome P-450
      (CYP) inhibitor, antioxidant, MAPK inhibitor, and Nrf2 RNAi, were used to
      delineate the signaling pathway. (-)Sch B caused a time-dependent activation of
      MAPK in H9c2 cells, with the degree of ERK activation being much larger than that
      of p38 or JNK. The MAPK activation was followed by an increase in the level of
      nuclear Nrf2, an indirect measure of Nrf2 activation, and the eliciting of a
      glutathione antioxidant response. The activation of MAPK and Nrf2 seemed to
      involve oxidants generated from a CYP-catalyzed reaction with (-)Sch B. Both ERK
      inhibition by U0126 and Nrf2 suppression by Nrf2 RNAi transfection largely
      abolished the cytoprotection against hypoxia/reoxygenation-induced apoptosis in (
      )Sch B-pretreated cells. (-)Sch B pretreatment potentiated the reoxygenation
      induced ERK activation, whereas both p38 and JNK activations were suppressed.
      Under the condition of ERK inhibition, Sch B treatment did not protect against
      ischemia/reperfusion injury in an ex vivo rat heart model. The results indicate
      that (-)Sch B triggers a redox-sensitive ERK/Nrf2 signaling, which then elicits a
      cellular glutathione antioxidant response and protects against
      hypoxia/reoxygenation-induced apoptosis in H9c2 cells. The ERK-mediated signaling
      is also likely involved in the cardioprotection afforded by Sch B in vivo.

PMID- 21193950
TI  - Thoracic outlet syndrome: definition, aetiological factors, diagnosis, management
      and occupational impact.
AB  - INTRODUCTION: Thoracic outlet syndrome is a controversial cause of neck and
      shoulder pain due to complex mechanisms involving muscular dysfunction and nerve
      compression. Although management of thoracic outlet syndrome must be based on a
      multidisciplinary approach, physicians and occupational therapist should be
      familiar with the principles of diagnosis and treatment. METHOD, RESULTS AND
      CONCLUSION: The purpose of this article is to review the definitions, diagnosis
      and management of this syndrome. A particular emphasis was described on the links
      between the workplace and the individual in the pathogenesis, prevalence in the
      workforce and the course of this disease.

PMID- 21193951
TI  - Barriers to adopting and implementing local-level tobacco control policies.
AB  - Although California communities have been relatively successful in adopting and
      implementing a wide range of local tobacco control policies, the process has not
      been without its setbacks and barriers. Little is known about local policy
      adoption, and this paper examines these processes related to adopting and
      implementing outdoor smoke-free policies, focusing on the major barriers faced by
      local-level tobacco control organizations in this process. Ninety-six projects
      funded by the California Tobacco Control Program submitted final evaluation
      reports pertaining to an outdoor smoking objective, and the reports from these
      projects were analyzed. The barriers were grouped in three primary areas:
      politically polarizing barriers, organizational barriers, and local political
      orientation. The barriers identified in this study underscore the need for an
      organized action plan in adopting local tobacco policy. The authors also suggest
      potential strategies to offset the barriers, including: (1) having a "champion"
      who helps to carry an objective forward; (2) tapping into a pool of youth
      volunteers; (3) collecting and using local data as a persuasive tool; (4)
      educating the community in smoke-free policy efforts; (5) working strategically
      within the local political climate; and (6) demonstrating to policymakers the
      constituent support for proposed policy.

PMID- 21193952
TI  - VGluT2 and NMDAR1 expression in cells in the inflammatory infiltrates in
      experimentally induced myositis: evidence of local glutamate signaling suggests
      autocrine/paracrine effects in an overuse injury model.
AB  - It is not known whether a glutamate signaling system is involved in muscle
      inflammation (myositis). In the present study, we examined this question in the
      soleus muscle in a laboratory model of myositis resulting from repetitive overuse
      induced by electrical stimulation and injection of pro-inflammatory substances.
      Sections of rabbit soleus muscle with an induced myositis, i.e., exhibiting
      infiltration of inflammatory cells, were examined immunohistochemically using
      antibodies against vesicular glutamate transporter VGluT2 and the glutamate
      receptor NMDAR1. In situ hybridization for demonstration of VGluT2 mRNA was also
      performed. Specific reactions for both VGluT2 and NMDAR1 could be observed
      immunohistochemically in the same cells. In situ hybridization demonstrated the
      occurrence of VGluT2 mRNA in the cells. Double staining showed that the VGluT2
      reactions were detectable in cells marked with T cell/neutrophil marker and in
      cells expressing eosinophil peroxidase. These data suggest the occurrence of
      previously unknown glutamate-mediated autocrine/paracrine effects within the
      inflammatory infiltrates during the development of muscle inflammation.

PMID- 21193953
TI  - Genomic evidence of intraspecific recombination in sugarcane mosaic virus.
AB  - The sugarcane mosaic virus (SCMV) of the genus potyvirus, which primarily affects
      maize, sugarcane, sorghum, abaca, and grasses, occurs worldwide and causes
      significant economic loss. Using the full genome sequences of SCMV and several
      recombination detection methods, in this study we report that recombination is
      the major driving force in the evolution and emergence of several new variants of
      SCMV. We reported eight highly significant (P < 0.001) recombination break
      points, majority of which are located within 6K1-VPg-NIaPro-NIb region, thus
      indicating a region for recombination hotspot. The observation of commonalities
      of same recombination events among the SCMV isolates between the countries (Spain
      and Mexico), and within the country (within China, and within Mexico), suggests
      common origin of the isolates in respective regions.

PMID- 21193954
TI  - The roles of COMT val158met status and aviation expertise in flight simulator
      performance and cognitive ability.
AB  - The polymorphic variation in the val158met position of the catechol-O
      methyltransferase (COMT) gene is associated with differences in executive
      performance, processing speed, and attention. The purpose of this study is: (1)
      replicate previous COMT val158met findings on cognitive performance; (2)
      determine whether COMT val158met effects extend to a real-world task, aircraft
      navigation performance in a flight simulator; and (3) determine if aviation
      expertise moderates any effect of COMT val158met status on flight simulator
      performance. One hundred seventy two pilots aged 41-69 years, who varied in level
      of aviation training and experience, completed flight simulator, cognitive, and
      genetic assessments. Results indicate that although no COMT effect was found for
      an overall measure of flight performance, a positive effect of the met allele was
      detected for two aspects of cognitive ability: executive functioning and working
      memory performance. Pilots with the met/met genotype benefited more from
      increased levels of expertise than other participants on a traffic avoidance
      measure, which is a component of flight simulator performance. These preliminary
      results indicate that COMT val158met polymorphic variation can affect a real
      world task.

PMID- 21193955
TI  - Genetic covariation underlying reading, language and related measures in a sample
      selected for specific language impairment.
AB  - Specific language impairment is a developmental language disorder characterized
      by failure to develop language normally in the absence of a specific cause.
      Previous twin studies have documented the heritability of reading and language
      measures as well as the genetic correlation between those measures. This paper
      presents results from an alternative to the classical twin designs by estimating
      heritability from extended pedigrees. These pedigrees were previously studied as
      part of series of molecular genetic studies of specific language impairment where
      the strongest genetic findings were with reading phenotypes rather than language
      despite selecting pedigrees based on language impairments. To explore the
      relationship between reading and language in these pedigrees, variance components
      estimates of heritability of reading and language measures were conducted showing
      general agreement with the twin literature, as were genetics correlations between
      reading and language. Phonological short-term memory, phonological awareness and
      auditory processing were evaluated as candidate mediators of the reading-language
      genetic correlations. Only phonological awareness showed significant genetic
      correlations with all reading measures and several language measures while
      phonological short-term memory and auditory processing did not.

PMID- 21193956
TI  - Assessment of coastal storm impacts on contaminant body burdens of oysters
      collected from the Gulf of Mexico.
AB  - This study evaluated changes in oyster tissue contaminant levels following North
      Atlantic tropical cyclones to determine if changes in contaminant concentrations
      were predictable. The basis for this study was analysis of coastal chemical
      contaminant data from the National Oceanic and Atmospheric Administration's
      (NOAA) National Status and Trends Mussel Watch Program and NOAA's National
      Weather Service storm track data. The tendency for contaminant (metals and
      organic compounds) body burdens to increase or decrease in oyster tissue after a
      storm was assessed using contingency and correspondence analyses. Post-storm
      contaminant levels in oysters revealed a consistent pattern of distribution,
      which could be described as follows: (1) most of the organic contaminants stay
      within their long-term concentration ranges, (2) very few organic contaminants
      decreased, and (3) metals overwhelmingly tend to increase.

PMID- 21193957
TI  - Epidemiology and outcome of the cardio-renal syndrome.
AB  - Cardiac and kidney disease are common, increasingly encountered and often co
      exist. Recently, the Acute Dialysis Quality Initiative (ADQI) Working Group
      convened a consensus conference to develop a classification scheme for the CRS
      and for five discrete subtypes. These CRS subtypes likely share pathophysiologic
      mechanisms, however, also have distinguishing clinical features, in terms of
      precipitating events, risk identification, natural history and outcomes.
      Knowledge of the epidemiology of heart-kidney interaction stratified by the
      proposed CRS subtypes is increasingly important for understanding the overall
      burden of disease for each CRS subtype, along with associated morbidity,
      mortality and health resource utilization. Likewise, an understanding of the
      epidemiology of CRS is necessary for characterizing whether there exists
      important knowledge gaps and to aid the in the design of clinical studies. In the
      most recent European and American guidelines for heart failure management, acute
      kidney injury and dysfunction were considered an index of poor prognosis.
      Paradoxically, however, in many randomized trials of interventions for patients
      with heart failure, those with kidney injury or dysfunction are often excluded.
      This review will provide a summary of the epidemiology of the cardio-renal
      syndrome and its subtypes.

PMID- 21193958
TI  - Comparison of GAD65 and 67 immunoreactivity in the lumbar spinal cord between
      young adult and aged dogs.
AB  - We investigated distribution and age-related changes in two isoforms of GABA
      synthesizing enzymes, glutamic acid decarboxylase (GAD) 65 and 67, in the lumbar
      levels (L(5)-L(6)) of the dog spinal cord. Male German shepherds were used at 1-2
      years (young adult dogs) and 10-12 years (aged dogs) of age. GAD65 immunoreaction
      was observed in neuropil, not in cell bodies, in all laminae of the adult lumbar
      spinal cord: Many punctate GAD65-immunoreactive structures were shown in all
      laminae. The density of GAD65 immunoreactive structures was highest in laminae I
      III, and lowest in lamina VII. In the aged dog, the distribution pattern of GAD65
      immunoreactivity was similar to that in the adult dog; however the density of
      GAD65-immunoreactive structures and its protein levels were significantly
      increased in the aged lumbar spinal cord. GAD67 immunoreaction in the adult dog
      was also distributed in all laminae of the lumbar spinal cord like GAD65;
      however, we found that small GAD67-immunoreactive cell bodies were observed in
      laminae II, III and VIII. In the aged dogs, GAD67 immunoreactivity and its
      protein levels were also increased compared to those in the adult group. In
      conclusion, our results indicate that the distribution of GAD65-immunoreactive
      structures is different from GAD67-immunoreactive structures and that their
      immunoreactivity in the aged dogs is much higher than the adult dogs.

PMID- 21193959
TI  - Comparison of equine bone marrow-, umbilical cord matrix and amniotic fluid
      derived progenitor cells.
AB  - The aim of the study was to compare in vitro the stemness features of horse
      progenitor cells derived from bone marrow (BM-MSCs), amniotic fluid (AF-MSCs) and
      umbilical cord matrix (EUC-MSCs). It has been suggested that there may be a stem
      cell population within both umbilical cord matrix and amniotic fluid. However,
      little knowledge exists about the characteristics of these progenitor cells
      within these sources in the equine species. This study wanted to investigate an
      alternative and non-invasive stem cell source for the equine tissue engineering
      and to learn more about the properties of these cells for future cell banking.
      Bone marrow, umbilical cord and amniotic fluid samples were harvested from
      different horses. Cells were analyzed for proliferation, immunocytochemical, stem
      cell gene expression and multilineage plasticity. BM- and AF-MSCs took similar
      time to reach confluence and showed comparable plating efficiency. All cell lines
      expressed identical stem cell markers and capability to differentiate towards
      osteogenic lineage. Almost all cell lines differentiated into the adipogenic
      lineage as demonstrated by cytochemical staining, even if no adipose gene
      expression was detectable for AF-MSCs. AF- and EUC-MSCs showed a limited
      chondrogenic differentiation compared with BM-MSCs as demonstrated by
      histological and biochemical analyses. These findings suggest that AF-MSCs
      appeared to be a readily obtainable and highly proliferative cell line from an
      uninvasive source that may represent a good model system for stem cell biology.
      More studies are needed to investigate their multilineage potential. EUC-MSCs
      need to be further investigated regarding their particular behavior in vitro
      represented by spheroid formation.

PMID- 21193960
TI  - Evaluation of genotype-specific survival using joint analysis of genetic and non
      genetic subsamples of longitudinal data.
AB  - Small sample size of genetic data is often a limiting factor for desirable
      accuracy of estimated genetic effects on age-specific risks and survival.
      Longitudinal non-genetic data containing information on survival or disease
      onsets of study participants for whom the genetic data were not collected may
      provide an additional "reserve" for increasing the accuracy of respective
      estimates. We present a novel method for joint analyses of "genetic" (covering
      individuals for whom both genetic information and mortality/morbidity data are
      available) and "non-genetic" (covering individuals for whom only
      mortality/morbidity data were collected) subsamples of longitudinal data. Our
      simulation studies show substantial increase in the accuracy of estimates in such
      joint analyses compared to analyses based on genetic subsample alone. Application
      of this method to analysis of the effect of common apolipoprotein E (APOE)
      polymorphism on survival using combined genetic and non-genetic subsamples of the
      Framingham Heart Study original cohort data showed that female, but not male,
      carriers of the APOE e4 allele have significantly worse survival than non
      carriers, whereas empirical analyses did not produce any significant results for
      either sex.

PMID- 21193961
TI  - Role of Bruton's tyrosine kinase in macrophage apoptosis.
AB  - Macrophages and polymorphonuclear cells (PMNs) rapidly respond to microbial and
      immune inflammatory stimuli and die during these responses. We have shown earlier
      that many macrophage and PMN functions are compromised in x-linked
      immunodeficient (Xid) mice with functional deficiency in Bruton's tyrosine kinase
      (Btk). We now report that Btk-deficient macrophages show enhanced susceptibility
      to apoptotic death on exposure to the microbial and immune inflammatory signals
      bacterial lipopolysaccharide (LPS) and interferon-gamma (IFNgamma) in vitro. In
      vivo in mixed bone marrow (BM) chimeras Btk deficiency leads primarily to loss of
      peripheral macrophage numbers without affecting BM development, suggesting a role
      of inflammation-induced apoptosis in regulating macrophage life span.
      Surprisingly, Btk deficiency does not affect macrophage apoptosis induced by DNA
      damage or CD95 engagement. Reactive nitrogen and oxygen species also do not
      contribute to inflammation-induced apoptosis, but apoptotic process involves loss
      of mitochondrial potential, shows increased activation of caspase 9 and enhanced
      loss of Bcl-xL. The lack of pro-survival signaling through the Btk
      phosphotidylinositol 3-kinase-Akt pathway, and persistent MEK signaling, lead to
      enhanced death in Btk-deficient macrophages only downstream of inflammatory
      triggers. These data underline the complex role of Btk in the regulation of
      macrophage survival and function.

PMID- 21193962
TI  - Telomerase activity-independent function of TERT allows glioma cells to attain
      cancer stem cell characteristics by inducing EGFR expression.
AB  - Telomerase reverse transcriptase (TERT), the catalytic subunit of the enzyme
      telomerase, is robustly expressed in cancer cells. TERT enables cells to avoid
      chromosome shortening during repeated replication by maintaining telomere length.
      However, several lines of evidence indicate that many cancer cells exhibit
      shorter telomere length than normal tissues, implying an additional function of
      TERT in tumor formation and progression. Here, we report a telomerase activity
      independent function of TERT that induces cancer stemness in glioma cells.
      Overexpression of TERT712, a telomerase activity-deficient form of TERT, in U87MG
      cells promoted cell self-renewal in vitro, and induced EGFR expression and
      formation of gliomas exhibiting cellular heterogeneity in vivo. In patients with
      glioblastoma multiforme, TERT expression showed a high correlation with EGFR
      expression, which is closely linked to the stemness gene signature. Induction of
      differentiation and TERT-knockdown in glioma stem cells led to a marked reduction
      in EGFR expression, cancer stemness, and anticancer drug resistance. Together,
      our findings indicate that TERT plays a crucial role in tumor progression by
      promoting cancer stemness through expression of EGFR.

PMID- 21193964
TI  - Investigating the structural and functional effects of mutating Asn glycosylation
      sites of horseradish peroxidase to Asp.
AB  - Horseradish peroxidase (HRP) has long attracted intense research interest and is
      used in many biotechnological fields, including diagnostics, biosensors, and
      biocatalysis. Enhancement of HRP catalytic activity and/or stability would
      further increase its applications. One of the problems with heterologus
      expression of HRP especially in prokaryotic host is lack of glycosylation that
      affects it's stability toward H(2)O(2) and thermal inactivation. In this study,
      two asparagine residues which constitute two of the eight glycosylation sites in
      native HRP (Asn 13 and 268) with respectively 83% and 65% surface accessibility
      were substituted with aspartic acid in recombinant HRP. Both mutant proteins
      expressed in Escherichia coli showed increased stabilities against heat (increase
      in t (1/2) from 20 min in native rHRP to 32 and 67 min in N13D and N268D) and
      H(2)O(2) (up to threefold). Unexpectedly, despite the distance of the mutated
      positions from the active site, notable alterations in steady-state k (cat) and K
      (m) values occurred with phenol/4-aminoantipyrine as reducing substrate which
      might be due to conformational changes. No significant alteration in flexibility
      was detected by acrylamide quenching analyses, but ANS binding experiments
      purposed lesser binding of ANS to hydrophobic patches in mutated HRPs. Double
      mutation was non-additive and non-synergistic.

PMID- 21193963
TI  - Infertility, cancer, and changing gender norms.
AB  - INTRODUCTION: Recent improvements in cancer detection, treatment, and technology
      have increased survivorship rates. These same life-saving treatments, however,
      can lead to infertility or sterility. Oncofertility, an emerging field at the
      intersection of cancer and oncology, centers on providing cancer patients with
      the potential to preserve their biological fertility. METHODS: We examine the
      history of how men and women have been treated for infertility and analyze
      contemporary studies of how women without cancer respond to infertility. RESULTS:
      Both female and male cancer patients and survivors value their fertility,
      although there is conflicting evidence on the degree to which women and men value
      fertility. Some studies have found that women and men value their fertility
      equally while others found that women value their fertility more than men.
      Gendered norms around fertility and parenthood seem to be changing, which may
      minimize these discrepancies. DISCUSSIONS/CONCLUSIONS: Although oncofertility is
      a nascent field, infertility is a historically relevant medical condition that is
      characterized by gendered narratives and norms. An analysis of the historical
      evolution of the understanding and treatment of infertility leads insight into
      modern conceptualizations of infertility both generally and in the case of
      cancer. Understanding these historical and current gendered influences helps to
      define the current context in which cancer patients are confronting potential
      infertility. IMPLICATIONS FOR CANCER SURVIVORS: The insight gained from this
      analysis can be used to inform clinical practice, offering guidance to healthcare
      providers approaching cancer patients about potential infertility, regardless of
      gender.

PMID- 21193966
TI  - Lung fluorescence imaging to evaluate tumor metastasis induced by AQP5 expression
      in murine model.
AB  - Our recent study, by up-regulation of AQP5 expression, showed enhanced
      proliferation and migration potential in lung cancer. However, so far none of the
      in vivo study of gene silencing of AQP5 has been tested. In this study, we tested
      roles of AQP5 on lung cancer metastasis potential by gene silencing of AQP5 in
      two lung cancer cell lines and tried to monitor lung metastases with EGFP marker.
      Lungs were imaged at different time points and allowed an accurate evaluation of
      tumor burden over time. Our results showed significantly decreased metastasis
      potential in AQP5 gene-silencing cells. Lung imaging confirmed the frequency of
      metastasis in mice. These data provide more evidence that AQP5 plays important
      roles in the metastasis potential of lung cancer. Lung fluorescence imaging
      provides rapid monitoring for tumor growth and metastasis, and it also offers
      quantitative and sensitive analysis of tumor growth and metastasis, compared to
      the traditional histology technique.

PMID- 21193965
TI  - Vascular endothelial growth factor increases permeability of the blood-tumor
      barrier via caveolae-mediated transcellular pathway.
AB  - The first goal of this study was to determine the effect of vascular endothelial
      growth factor (VEGF) on permeability of the blood-tumor barrier (BTB). The second
      goal was to determine possible cellular mechanisms by which VEGF increases
      permeability of the BTB. In the rat C6 glioma model, the permeability of the BTB
      was significantly increased after VEGF injection at dose of 0.05 ng/g and reached
      its peak at 45 min. Meanwhile, we observed that the density of pinocytotic
      vesicles of brain microvascular endothelial cells (BMECs) in the BTB increased
      dramatically by transmission electron microscopy. The immunohistochemistry and
      western blot analysis revealed that the expression level of caveolae structure
      proteins caveolin-1 and caveolin-2 in BMECs was increased after VEGF injection,
      peaked at 45 min, and then decreased to the untreated level. The time peak of
      expression level of caveolin-1 and caveolin-2 was identical with the peak time of
      permeability of the BTB and the density of pinocytotic vesicles. All of these
      results strongly indicated that VEGF increased permeability of the BTB caused by
      enhancement of the density of pinocytotic vesicles, and the molecular mechanism
      might be associated with upregulated expression of caveolin-1 and caveolin-2.

PMID- 21193967
TI  - Synchronous and metachronous bilateral breast cancer: a long-term single
      institution experience.
AB  - Bilateral breast cancer (bBC) is the most common 2nd tumor in primary BC
      patients. However, its natural history is poorly understood as is the effect of
      previous adjuvant therapies. Between 1980 and 2005, we identified 3757 BC
      patients treated in our Institution, with 120 (3.2%) cases of bBC, 91 (2.4%) were
      metachronous BC (mBC), 29 (0.8%) synchronous BC (sBC). sBC defined as found
      before 3 months of the initial diagnosis. We performed a descriptive and an
      overall survival (OS) analysis. mBC appeared in young patients with a strong
      family history of BC. Most were diagnosed mammographically. The risk did not
      disappear after 15 years of follow-up. In most estrogen receptor (ER)-positive
      cases, the 2nd tumor was also ER-positive (concordance rate of 91%). No
      differences were seen according to the previous use of tamoxifen. In ER-negative
      cases, 43% of mBC were ER-positive. Synchronous BC (sBC) appeared in an elderly
      population with a strong family history. About 76% were ER-positive. ER status
      concordance was seen in 62%. There were no statistically significant differences
      in OS between patients with sBC or those with the 2nd mBC. A shorter time to
      appearance of the 2nd tumor predicted a worse OS. ER negativity and grade 3
      tumors were negative prognostic factors. The risk of mBC does not abate with the
      pass of time. Contralateral mammographies should form part of follow-up. ER
      status concordance is high, especially in ER-positive cases. No differences were
      seen according to previous use of tamoxifen. Shorter disease-free intervals were
      linked with worse OS.

PMID- 21193968
TI  - Clinical prognostic analysis of 116 patients with primary intestinal non-Hodgkin
      lymphoma.
AB  - The gastrointestinal tract is the most common extranodal invasion site of non
      Hodgkin lymphoma (NHL). Primary gastrointestinal NHL is often discussed together
      in most survival analyses. Primary intestinal NHL is significantly different from
      primary gastric NHL with regard to clinical features, pathological subtype,
      treatment, and prognosis. In this article, we analyzed clinical and pathological
      characteristics of primary intestinal NHL, and we also explored prognostic
      factors for primary intestinal NHL. A retrospective analysis was carried out on
      clinical data from 116 cases of confirmed primary intestinal NHL. The Kaplan
      Meier method was used for the survival analysis. A Cox model was used for a
      multivariate analysis. In 116 patients with primary intestinal NHL, 79 patients
      were men (68.1%) and 37 patients were women (31.9%). In the cases used in this
      study, 68 were B-cell NHL and 48 were T-cell NHL. The age, incidence of
      intestinal obstruction, B symptom and performance status (PS) were closely
      related with pathological subtype. One-year and two-year survival rates were 76.7
      and 58.3%, respectively. The log-rank univariate analysis showed male patients,
      PS score greater than or equal to two, hypoproteinemia, intestinal perforation, T
      cell type, late stage (III/IV), no radical surgery, and no chemotherapy had
      relatively poor prognoses. Cox multivariate analysis shown that gender (95.0% CI
      0.218-0.721), pathological subtype (95.0% CI 1.484-4.179), and radical surgery
      (95.0% CI 0.110-0.394) were independent prognostic risk factor for primary
      intestinal NHL. Male patients, T-cell intestinal lymphoma, and no radical surgery
      had rapid clinical processes and poor prognoses.

PMID- 21193969
TI  - Gemcitabine and cisplatin salvage regimen in heavily pretreated metastatic breast
      cancer: a Brazilian experience.
AB  - Gemcitabine and cisplatin combination (Gem-Cis) is a commonly used regimen in
      metastatic breast cancer (MBC), with proven activity in phase II trials. It is
      mostly used as a salvage regimen for progressive disease refractory to
      anthracyclines and taxanes, and when liver dysfunction secondary to liver
      metastasis precludes these drugs. Retrospective review of medical charts was
      conducted for patients treated with Gem-Cis for MBC in a single institution in
      Brazil between January 2004 and July 2007. The purpose of this study was to
      evaluate the outcomes and toxicity of Gem-Cis in a broad indication, including
      patients with deteriorated performance status (PS) and liver dysfunction, which
      were excluded from clinical trials. Fifty-six patients were included. Median age
      was 52 years, 46.4% were hormone-receptor negative, 57.2% received 3 or more
      prior chemotherapy lines, and 34 had liver metastasis. The median overall
      survival (OS) was 7.6 months, the median progression-free survival was 3.3
      months, and the response rate was 21.2%. In variable analysis, PS was
      significantly associated with OS, even after adjusting to other factors.
      Toxicities included grades 3 or 4 anemia in 19.3%, neutropenia in 21.1%, and
      thrombocytopenia in 12.3%. Gem-Cis was a relatively active combination in this
      population that typically carries a poor prognosis. The subgroup of patients with
      favorable PS experienced longer survival, even when liver metastasis and hepatic
      dysfunction were a concern. Toxicity was manageable and it was not correlated
      with PS or liver dysfunction.

PMID- 21193970
TI  - Spectrum of kawasaki disease.
AB  - The authors report 22 patients of Kawasaki disease, diagnosed and treated over a
      period of 3 years at a tertiary care centre in New Delhi. Ten cases fullfiled the
      criteria of a "classical" case while 12 cases were "incomplete" cases.
      Echocardiography was performed in all cases and coronary artery involvement was
      found in 8 (36%) cases. All cases received high dose Intravenous Immunoglobulins
      (IVIG) as standard therapy. In two cases, a repeat dose of IVIG was required for
      defervescence to occur. All cases recovered after therapy. Those with coronary
      artery involvement were planned for a 2 years follow up from the time of
      diagnosis.

PMID- 21193971
TI  - Diagnostic dilemma of JMML coexisting with CMV infection.
AB  - Juvenile myelomonocytic leukemia (JMML) is a rare mixed myeloproliferative and
      myelodysplastic disorder of early childhood, characterized by excessive
      proliferation of monocytic and granulocytic cells, along with myelodysplastic
      features. There are reports of viral infections mimicking JMML, with all clinical
      and hematological parameters normalizing on resolution of infection. The authors
      describe a 1- year- old boy with concomitant JMML and CMV infection. The
      diagnostic dilemma, the significance of distinguishing it from a mimicking viral
      infection, as well as potential synergistic effect of concomitant infections on
      the presentation or actual disease severity of underlying JMML will be discussed.

PMID- 21193972
TI  - Supportive care of a critically ill child.
AB  - The goal of pediatric intensive care is early identification, severity assessment
      and resuscitation of critical patients by utilizing standardized protocols. The
      primary or precipitating disorder should be the focus of attention and specific
      intervention. But in order to provide holistic care to a patient, due attention
      should also be rendered to supportive care. Monitoring of sick children in PICU
      is an essential part of management. Various monitoring technologies add to the
      clinical monitoring but cannot replace clinical monitoring. The treating team
      should follow a checklist to ensure all aspects of supportive care are taken care
      of in every patient. Due attention should be paid to glucose control, skin and
      eye care, oral hygiene, prevention of stress ulcer, care of various lines and
      catheters and prevention of nosocomial infections.

PMID- 21193974
TI  - Status of iodine content of salt in four regions of India.
AB  - OBJECTIVE: To study the Status of Iodine Content of Salt in four regions of
      India. METHODS: At each of the four centers (Vadodara, Dibrugarh, Jodhpur, New
      Delhi), High Schools were selected randomly from list of schools obtained from
      district education office and more than 700 salt samples were selected from each
      center. A total of 3,010 salt samples were collected from students of High
      Schools (consumed at their households), selected randomly from four centers and
      iodine content of salt by Standard Iodometric Titration Method (IT) was
      estimated. RESULTS: Analysis revealed that majority of salt sample collected at 4
      centers were of powdered variety of salt. Analysis of iodine content in salt by
      IT method revealed that high proportion of school children (51.6%) consumed salt
      having inadequate iodine content (salt samples with less than 15 ppm of iodine)
      in Jodhpur district followed by Vadodara (19.8%), New Delhi (8.5%) and least in
      Dibrugarh (1.2%). The percentage of consumption of adequately iodized salt was
      highest in Dibrugarh (98.8%) among the four regions of India. CONCLUSIONS: Status
      of iodine content is varying from state to state i.e. highest at Dibrugarh and
      lowest at Jodhpur. This indicates that consumption of iodized salt in Jodhpur is
      low and needs more attention. Government may adopt different strategies in
      different states. There is a strong need of iodization of salt in addition to
      creating awareness among rural inhabitants for consumption of iodized salt
      especially in Jodhpur District. More attention is required for monitoring quality
      of iodized salt available in the community.

PMID- 21193973
TI  - Multi-drug resistant childhood tuberculosis.
AB  - Emergence of drug resistant tuberculosis is one of the major challenges faced by
      health community globally. Tuberculosis is an important cause of morbidity and
      mortality among children in endemic areas, yet little is known regarding
      epidemiology of pediatric tuberculosis and even far lesser information is
      available about epidemiology, diagnosis, management and treatment outcome of drug
      resistant tuberculosis in children. Despite limited data and difficulties in its
      management, drug resistant tuberculosis can be successfully treated even in
      resource poor settings with proper use of existing technologies. A high index of
      suspicion and early drug susceptibility testing is the key to early diagnosis and
      good treatment outcome. Difficulties in establishing the diagnosis, drug
      toxicities and absence of pediatric formulations add challenges to the management
      of Pediatric MDR TB Cases. Active research is required to answer the unresolved
      issues of finding optimal diagnostic tools, treatment regimens and duration and
      chemoprophylaxis in pediatric drug resistant tuberculosis.

PMID- 21193975
TI  - Pain response in newborns to the order of injecting BCG and Hepatitis-B vaccines:
      a randomized trial.
AB  - OBJECTIVE: To determine if acute pain response after administration of the BCG
      vaccine and the Hepatitis-B vaccine is affected by the order in which they are
      given. METHODS: This Single-center randomized clinical trial was conducted in the
      Vaccination room in the Pediatrics Outpatient Department at KVG Medical College;
      Karnataka, India. 76 healthy term neonates undergoing routine immunization were
      included in this study. Newborns received either BCG vaccine or the Hepatitis-B
      vaccine first, followed by the other vaccine. The primary outcome was neonatal
      pain during vaccine injection as assessed by a validated measure, the Neonatal
      Infant Pain Scale (NIPS), scored by resident doctors blinded to the study purpose
      and hypothesis. In addition, a nurse rated pain using a 10-cm visual analog
      scale(VAS). RESULTS: A total of 76 infants participated: 38 received the BCG
      vaccine first and 38 received the Hepatitis-B vaccine first. Demographic
      characteristics did not differ between the groups. Overall mean (SD) pain scores
      per neonate were significantly lower when BCG was administered first compared to
      the order when Hepatitis-B vaccine was administered first (for NIPS 5.55 [0.54]
      vs. 5.84 [0.29], P = .005; for VAS, 6.25 [0.80] vs. 6.58 [0.54], P = .04). When
      given first, the BCG vaccine caused significantly less pain (P < .001)than the
      Hepatitis-B, as assessed by the NIPS and VAS (P < .001). CONCLUSIONS: Pain was
      reduced when the BCG vaccine was administered before the Hepatitis-B in neonates
      undergoing routine vaccination. The authors recommend that the order of vaccine
      injections be the BCG vaccine followed by Hepatitis-B.

PMID- 21193976
TI  - Arrhythmogenic dilated cardiomyopathy due to a novel mutation in the desmoplakin
      gene.
AB  - The authors describe an 11-year-old girl who presented with congestive heart
      failure due to arrhythmogenic dilated cardiomyopathy. She had curly, woolly hair
      since birth and palmoplantar keratoderma. Molecular genetic analysis of the
      desmoplakin gene revealed that she was homozygous for the c.3901C>T (p.Gln1301X)
      change in exon 23 of the desmoplakin (DSP) gene, confirming the diagnosis of
      Carvajal disease. As per the Arrhythmogenic Right Ventricular Dysplasia/
      Cardiomyopathy Genetic Variants Database, this is a novel mutation. She was
      managed with diuretics, enalapril, carvedilol and amiodarone, is presently
      stable, and on regular follow-up. Carvajal disease is a rare cardiocutaneous
      disorder and few cases have been reported in the literature. The authors review
      the published cases of the Naxos-Carvajal phenotype from India. Pediatricians
      need to be aware of this clinical entity whenever arrhythmogenic dilated
      cardiomyopathy is associated with woolly hair and/or palmoplantar keratoderma.

PMID- 21193977
TI  - Predictors of adherence to secondary preventive medication in stroke patients.
AB  - OBJECTIVE: The purpose of this study is to identify factors which predict
      adherence in stroke survivors. DESIGN: This is a longitudinal study where 180
      stroke survivors were assessed 1 year after their first ischaemic stroke. The
      relationship between adherence and illness and medication beliefs was tested at
      baseline (time 1) and again 5-6 weeks later (time 2). MAIN OUTCOME MEASURES: The
      main outcome measures used in this study are Medication Adherence Report Scale
      and urinary salicylate levels. RESULTS: Four variables predicted time 1 poor
      adherence: (1) younger age, (2) increased specific concerns about medications,
      (3) reduced cognitive functioning and (4) low perceived benefit of medication.
      Three out of these four variables were again predictive of time 2 adherence and
      accounted for 24% of the variance: (1) younger age, (2) increased specific
      concerns about medications and (3) low perceived benefit of medication. The
      urinary salicylate assay failed to differentiate between patients taking and not
      taking aspirin. CONCLUSION: Interventions to improve adherence should target
      patients' beliefs about their medication.

PMID- 21193978
TI  - A technique for treating patello-femoral instability in immature patients: the
      tibial tubercle periosteum transfer.
AB  - Patello-femoral problems are frequently encountered in knee clinic. The most
      important role of the patella is to increase the quadriceps efficiency, although
      this function could be altered in the patello-femoral instability. Active
      stability of the patello-femoral joint is provided by the surrounding muscles and
      ligaments, passive stability is provided by the bony and cartilage structures.
      Patellofemoral instability is defined, from Henry Dejour, as a disease without
      engagement the patella in the femoral trochlea during knee range of motion. Every
      time should be performed careful radiological preoperative investigations
      (radiographs and computed tomography) involving an expert musculoskeletal
      radiologist. Surgical procedures may be divided into those that address the soft
      tissues (muscles and ligaments), generally on the immature skeletal, and those
      that effect bony changes, generally on the mature skeletal; sometimes, it is
      necessary to combine soft-tissue and bony procedures. In this report, the authors
      describe a tibial tubercle periosteum transfer technique for patello-femoral
      instability in immature patients, which may potentially improve clinical results
      in very young symptomatic patients with patello-femoral instability.

PMID- 21193979
TI  - Lymphoproliferative disorders after solid organ transplantation-classification,
      incidence, risk factors, early detection and treatment options.
AB  - Posttransplant lymphoproliferative disorder (PTLD) is a heterogeneous disease
      group of benign and malignant entities. The new World Health Organisation
      classification introduced in 2008 distinguishes early lesions, polymorphic,
      monomorphic and classical Hodgkin lymphoma-type PTLD. Based on the time of
      appearance, early and late forms can be identified.PTLDs are the second most
      frequent posttransplantation tumors in adulthood, and the most frequent ones in
      childhood. The incidence varies with the transplanted organ-from 1%-2% following
      kidney transplantation to as high as 10% following thoracic organ transplantation
      due to different intensities in immunosuppression. Immunocompromised state and
      Epstein-Barr virus (EBV) infection are the two major risk factors.In Europe and
      the US approximately 85% of PTLDs are of B-cell origin, and the majority are EBV
      associated. Symptoms are often unspecific; extranodal, organ manifestations and
      central nervous system involvement is common. Early lesions respond well to a
      decrease in immunosuppression. Malignant entities are treated with rituximab,
      chemotherapy, radiotherapy and surgical therapy. Adoptive T-cell transfer
      represents a promising therapeutic approach. The prognosis is favorable in early
      PTLD, and poor in late PTLD. Five-year survival is 30% for high-grade lymphomas.
      The prognosis of EBV-negative lymphomas is worse.Lowering the risk of PTLD may be
      achieved by low dose maintenance immunosuppression, immunosuppressive drugs
      inhibiting cell proliferation, and special immunotherapy (e.g. interleukin-2
      inhibitors). Early detection is especially important for high risk-e.g. EBV
      negative-patients, where the appearance of EBV-DNA and the increase in its titer
      may help.

PMID- 21193980
TI  - Application of linear discriminant analysis and Attenuated Total Reflectance
      Fourier Transform Infrared microspectroscopy for diagnosis of colon cancer.
AB  - Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR)
      microspectroscopy was applied for detection of colon cancer according to the
      spectral features of colon tissues. Supervised classification models can be
      trained to identify the tissue type based on the spectroscopic fingerprint. A
      total of 78 colon tissues were used in spectroscopy studies. Major spectral
      differences were observed in 1,740-900 cm(-1) spectral region. Several
      chemometric methods such as analysis of variance (ANOVA), cluster analysis (CA)
      and linear discriminate analysis (LDA) were applied for classification of IR
      spectra. Utilizing the chemometric techniques, clear and reproducible differences
      were observed between the spectra of normal and cancer cases, suggesting that
      infrared microspectroscopy in conjunction with spectral data processing would be
      useful for diagnostic classification. Using LDA technique, the spectra were
      classified into cancer and normal tissue classes with an accuracy of 95.8%. The
      sensitivity and specificity was 100 and 93.1%, respectively.

PMID- 21193981
TI  - [Meningitis epidemic: assessment of surveillance and treatment of cases in the
      health centers of a Burkina Faso district].
AB  - Meningococcal meningitis remains a periodical threat in the African meningitis
      belt. The countries concerned, such as Burkina Faso, provided guidelines for its
      surveillance, diagnosis, treatment, and prevention during outbreaks. The
      objective of this study is to assess the quality of the surveillance system and
      case management during an outbreak in Fada N'Gourma district. A retrospective
      study of the meningitis outbreak in 2007 was conducted by literature review and
      interviews of health caretakers across 27 health centers (CSPS) and three units
      in the regional hospital in the district.We reported all data available about
      surveillance and case management, and then we compared it with the guidelines of
      the Ministry of Health. The case definition and notification forms were available
      in all centers and units. During the outbreak, 861 cases were recorded, but only
      89% was notified at the upper level and 87% of notification forms were available.
      The age is marked on all the forms, while the interval between the onset of
      symptoms and consultation is noted only in 90.7%. The forms were distributed
      weekly at the district level. Cerebrospinal fluid (CSF) Gram coloration was
      performed for a limited number of cases (150/349 samples, 42.9%); it showed Gram
      negative diplococcus in 86%. Culture was performed for a limited number of
      patients (7 cases). According to the results of a central level laboratory study,
      the outbreak was due to Group A Neisseria meningitidis. The case management
      guidelines were available in all the centers and units which were supervised
      during the outbreak. Anti-biotherapy was appropriate in 93.6% of the cases. A
      shortage of antibiotics (free prepositioning) was observed in 7 centers (23.3%).
      The mortality rate was 3.5%. This assessment shows an under-notification of
      cases, despite the existence of a surveillance system and supervision, a weak
      laboratory contribution in germ identification, appropriate case management, and
      shortage of antibiotics during the outbreak. Management of a meningitis outbreak
      may become more efficient by improving the notification, the laboratory's
      capabilities, and the availability of drugs.

PMID- 21193982
TI  - Re: sildenafil adjunctive therapy to risperidone in the treatment of the negative
      symptoms of schizophrenia.

PMID- 21193983
TI  - Mice lacking adenylyl cyclase type 5 (AC5) show increased ethanol consumption and
      reduced ethanol sensitivity.
AB  - RATIONALE: The adenylyl cyclase (AC)/cAMP system is believed to be a key
      component in regulating alcohol-drinking behavior. It was reported that adenylyl
      cyclase-5 (AC5) is expressed widely in the brain, with a preferential
      concentration in the dorsal striatum and nucleus accumbens, brain regions which
      are important for addiction and emotion. AC5 has been shown to be an essential
      mediator of morphine addiction and dopamine receptor function; however, it
      remains unknown whether or not AC5 plays a role in ethanol preference and
      sensitivity in animals. OBJECTIVE: This work was carried out to determine the
      role of AC5 in alcohol consumption and the hypnotic response to alcohol using AC5
      knockout (KO) mice. RESULTS: In the test for ethanol preference employing a two
      bottle free-choice paradigm, AC5 KO mice showed increased ethanol consumption and
      preference compared with the wild-type mice. Ethanol-induced hypothermia was
      weakly reduced in AC5 KO mice. AC5 KO mice exhibited sedation/behavioral sleep to
      high-dose ethanol, but their responses were greatly suppressed compared with the
      wild-type mice. CONCLUSIONS: These results suggest that AC5 is an important
      signaling molecule regulating alcohol sensitivity and preference in animals.
      These data provide critical information for AC5 activation as a candidate target
      for the treatment of alcoholism.

PMID- 21193984
TI  - Pharmacological characterization of social isolation-induced hyperactivity.
AB  - RATIONALE: Social isolation (SI) of rats directly after weaning is a non
      pharmacological, non-lesion animal model based on the neurodevelopmental
      hypothesis of schizophrenia. The model causes several neurobiological and
      behavioral alterations consistent with observations in schizophrenia. OBJECTIVES:
      In the present study, we evaluated if isolated rats display both a pre-pulse
      inhibition (PPI) deficit and hyperactivity. Furthermore, the sensitivity of SI
      hyperactivity to antipsychotic was evaluated. METHODS: Rats were socially
      isolated or group-housed for 12 weeks starting on postnatal day 25. In one batch
      of animals, the PPI and hyperactivity response were repeatedly compared.
      Furthermore, we investigated the robustness of the SI-induced hyperactivity by
      testing close to 50 batches of socially isolated or group-housed rats and tested
      the sensitivity of the assay to first- and second-generation antipsychotics,
      haloperidol, olanzapine, and risperidone, as well as the group II selective
      metabotrobic glutamate receptor agonist (LY404039). RESULTS: Socially isolated
      rats showed a minor PPI deficit and a robust increase in hyperactivity compared
      with controls. Furthermore, SI-induced hyperactivity was selectively reversed by
      all antipsychotics, as well as the potential new antipsychotic, LY404039.
      CONCLUSION: SI-induced hyperactivity was more pronounced and robust, as compared
      with SI-induced PPI deficits. Furthermore, SI-induced hyperactivity might be
      predictive for antipsychotic efficacy, as current treatment was effective in the
      model. Finally, using LY404039, a compound in development against schizophrenia,
      we have shown that the hyperactivity assay is sensitive to potential novel
      mechanisms of action. Thus, SI-induced hyperactivity might be a robust and novel
      in vivo screening assay of antipsychotic efficacy.

PMID- 21193988
TI  - Chemical inhibitors of methanogenesis and putative applications.
AB  - This mini-review summarizes the category, characteristics, and the application
      fields of the chemical methanogenic inhibitors. Usually, the chemical
      methanogenic inhibitors can be divided into "specific" and nonspecific
      inhibitors. The former group includes the structural analogs of coenzyme M and
      HMG-CoA inhibitors. The nonspecific group includes many chemicals which can
      inhibit the activity of both methanogens and non-methanogens. The chemical
      inhibitors of methanogenesis have been widely used in the fields of understanding
      methane production and consumption in pure culture or in complex natural
      environment, production of value-added substances, such as volatile fatty acids
      and hydrogen, and reduction of energy loss and improvement of the efficiency of
      ruminal energetic transformations. Finally, with an increasing understanding of
      the mechanistic effects of the chemical inhibitors of methanogenesis, it is
      possible that some could be used to develop into promising feed additives to
      reduce losses associated with enteric methane production or as useful tools to
      screen microbial consortia from various biotechnological applications to enhance
      hydrogen and acid production.

PMID- 21193989
TI  - The slow cell death response when screening chemotherapeutic agents.
AB  - PURPOSE: To examine the correlation between cell death and a common surrogate of
      death used in screening assays, we compared cell death responses to those
      obtained with the sulforhodamine B (SRB) cell protein-based "cytotoxicity" assay.
      METHOD: With the SRB assay, the Hill equation was used to obtain an IC50 and
      final cell mass, or cell mass present at infinite agent concentrations, with
      eight adherent cell lines and four agents (32 agent/cell combinations). Cells
      were treated with high agent concentrations (well above the SRB IC50) and the
      death response determined as the time-dependent decrease in cells failing to bind
      both annexin V and vital fluorochromes by flow cytometry. RESULTS: Death kinetics
      were categorized as fast (5/32) (similar to the reference nonadherent Jurkat
      line), slow (17/32), or none (10/32), despite positive responses in the SRB assay
      in all cases. With slow cell death, a single exposure to a chemotherapeutic agent
      caused a slow, progressive increase in dead (necrotic) and dying (apoptotic)
      cells for at least 72 h. CONCLUSIONS: Cell death (defined by annexin and/or
      fluorochrome binding) did not correlate with the standard SRB "cytotoxicity"
      assay. With the slow cell death response, a single exposure to an agent caused a
      slow conversion from vital to apoptotic and necrotic cells over at least 72 h
      (the longest time point examined). Here, increasing the time of exposure to agent
      concentrations modestly above the SRB IC50 provides a method of maximizing cell
      kill. If tumors respond similarly, sustained low doses of chemotherapeutic
      agents, rather than a log-kill, maximum tolerated dose strategy may be an optimal
      strategy of maximizing tumor cell death.

PMID- 21193990
TI  - A PTPN22 promoter polymorphism -1123G>C is associated with RA pathogenesis in
      Chinese.
AB  - The minor allele of the non-synonymous single nucleotide polymorphism (SNP)
      +1858C>T within the PTPN22 gene has now been unequivocally confirmed as
      conferring susceptibility to RA in population from Europe and America, but not in
      population from Asia. The aim of this study was to jointly address and integrate
      these separate findings to further elucidate the association between the PTPN22
      gene and RA in Chinese Hans of Guangdong province. Four hundred and ninety-four
      cases with RA and 496 healthy controls were randomly selected, their SNPs at
      position -1123G>C (rs2488457), +1858C>T (rs2476601), +788G>A (rs33996649), and
      rs1310182 were genotyped using PCR-RFLP, followed by agarose gel electrophoresis.
      +1858C>T (rs2476601) and +788G>A (rs33996649) are not polymorphic in Chinese
      Hans. Meanwhile, our result reveals that the degree of association between the
      promoter polymorphism, -1123G>C and RA, was analogous to that observed in
      Japanese reports (odds ratio [OR] = 1.517, 95% CI = [1.154-1.995], P = 0.003).
      Expression study also indicated a tendency for association between -1123G>C and
      PTPN22 gene expression. Our study underpins that the promoter polymorphism, 
      1123G/C, may be a causal SNP for RA in Asian.

PMID- 21193991
TI  - Malignancies associated with systemic lupus erythematosus in Taiwan: a nationwide
      population-based cohort study.
AB  - Patients with systemic lupus erythematosus (SLE) are suggestive to have a higher
      cancer risk. The aim of this study is to evaluate the possible association of
      malignancy and SLE in Taiwan. We used the data of the National Health Insurance
      system of Taiwan to assess this issue. The SLE cohort contained 2,150 patients,
      and each patient was randomly frequency matched to 8 people without SLE on age
      and sex. The Cox's proportion hazard regression analysis was conducted to
      estimate the effects of SLE on the cancer risk. In patients with SLE, the risk of
      developing overall cancer was marginally significantly higher [adjusted Hazard
      ratio (HR) = 1.26, 95% confidence interval (95% CI) = 0.99-1.59] and was
      significantly higher for developing prostate cancer (adjusted HR = 3.78, 95% CI =
      1.30-11.0). Our study unexpectedly found that Taiwanese patients with SLE have a
      higher risk to develop prostate cancer.

PMID- 21193992
TI  - Cognitive and functional outcome in spina bifida-Chiari II malformation.
AB  - PURPOSE: The long-term outcome in spina bifida-Chiari II-hydrocephalus complex is
      poorly understood. Traditional neurosurgical outcome measures are crude.
      Neuropsychological testing is increasingly important in outcome assessment. We
      investigated the health, disability, lifestyle and cognitive function in adults
      who had myelomeningocoele closure at birth. METHODS: Adult patients under routine
      follow-up were assessed in a joint neurosurgery/neuropsychology clinic. Patients
      completed lifestyle questionnaires, the hydrocephalus outcome questionnaire (HOQ)
      and underwent cognitive testing. Clinical variables including number of shunt
      revisions, shunt infection and surgical decompression of foramen magnum, which
      may influence outcome, were investigated. RESULTS: Twenty-one adults with a
      median age of 35 years were investigated. All had treated hydrocephalus, and
      eight had foramen magnum decompression for headache or progressive brainstem
      symptoms with stabilisation of symptoms in seven and improvement in one. Only
      eight patients were living independently, five were in paid employment and five
      work voluntarily. HOQ scores for cognitive function were lower (0.56 +/- 0.20;
      mean +/- standard deviation (SD)) than those for physical (0.64 +/- 0.15) and
      social-emotional (0.65 +/- 0.17) health. Cognitive function varied across the
      cohort with attention most severely affected (73.9 +/- 17.0; mean +/- SD).
      Repeated episodes of shunt malfunction or foramen magnum decompression were not
      associated with a worse cognitive function. CONCLUSIONS: Despite intervention in
      childhood and adequate cerebrospinal fluid diversion the prognosis for
      independent living into adulthood remains poor. All patients have elements of
      cognitive impairment. Structural brain abnormalities may be more important
      determinants of cognitive outcome than shunt malfunction.

PMID- 21193993
TI  - Embryology and bony malformations of the craniovertebral junction.
AB  - BACKGROUND: The embryology of the bony craniovertebral junction (CVJ) is reviewed
      with the purpose of explaining the genesis and unusual configurations of the
      numerous congenital malformations in this region. Functionally, the bony CVJ can
      be divided into a central pillar consisting of the basiocciput and dental pivot
      and a two-tiered ring revolving round the central pivot, comprising the foramen
      magnum rim and occipital condyles above and the atlantal ring below.
      Embryologically, the central pillar and the surrounding rings descend from
      different primordia, and accordingly, developmental anomalies at the CVJ can also
      be segregated into those affecting the central pillar and those affecting the
      surrounding rings, respectively. DISCUSSION: A logical classification of this
      seemingly unwieldy group of malformations is thus possible based on their
      ontogenetic lineage, morbid anatomy, and clinical relevance. Representative
      examples of the main constituents of this classification scheme are given, and
      their surgical treatments are selectively discussed.

PMID- 21193994
TI  - Major translocation of calcium upon epidermal barrier insult: imaging and
      quantification via FLIM/Fourier vector analysis.
AB  - Calcium controls an array of key events in keratinocytes and epidermis: localized
      changes in Ca(2+) concentrations and their regulation are therefore especially
      important to assess when observing epidermal barrier homeostasis and repair,
      neonatal barrier establishment, in differentiation, signaling, cell adhesion, and
      in various pathological states. Yet, tissue- and cellular Ca(2+) concentrations
      in physiologic and diseased states are only partially known, and difficult to
      measure. Prior observations on the Ca(2+) distribution in skin were based on
      Ca(2+) precipitation followed by electron microscopy, or proton-induced X-ray
      emission. Neither cellular and/or subcellular localization could be determined
      through these approaches. In cells in vitro, fluorescent dyes have been used
      extensively for ratiometric measurements of static and dynamic Ca(2+)
      concentrations, also assessing organelle Ca(2+) concentrations. For lack of
      better methods, these findings together build the basis for the current view of
      the role of Ca(2+) in epidermis, their limitations notwithstanding. Here we
      report a method using Calcium Green 5N as the calcium sensor and the phasor-plot
      approach to separate raw lifetime components. Thus, fluorescence lifetime imaging
      (FLIM) enables us to quantitatively assess and visualize dynamic changes of
      Ca(2+) at light-microscopic resolution in ex vivo biopsies of unfixed epidermis,
      in close to in vivo conditions. Comparing undisturbed epidermis with epidermis
      following a barrier insult revealed major shifts, and more importantly, a
      mobilization of high amounts of Ca(2+) shortly following barrier disruption, from
      intracellular stores. These results partially contradict the conventional view,
      where barrier insults abrogate a Ca(2+) gradient towards the stratum granulosum.
      Ca(2+) FLIM overcomes prior limitations in the observation of epidermal Ca(2+)
      dynamics, and will allow further insights into basic epidermal physiology.

PMID- 21193995
TI  - Perinatal complications in unaffected sisters of anorexia nervosa patients:
      testing a covariation model between genetic and environmental factors.
AB  - Although perinatal complications are hypothesized to be risk factors for the
      development of anorexia nervosa (AN), no study to date explored this issue using
      a discordant sibling design. This type of design allows to explore whether the
      risk for obstetric complications is itself a consequence of the genetic
      vulnerability for AN (covariation model) or whether obstetric complications
      increase the risk of AN independently of (additive model), or in interaction with
      (interaction model), the disorder's genetic liability. The presence of perinatal
      complications was assessed through review of the obstetric records of 60 AN
      subjects, 60 unaffected sisters, and 70 healthy subjects. Unaffected sisters and
      healthy controls were compared in relation to perinatal characteristics and
      complications. There was no evidence for an elevated rate of complications in
      unaffected siblings of AN patients. Mothers with a positive psychiatric history
      tended to have more perinatal complications. Perinatal complications seem to be
      independent risk factors that may interact with, but are not caused by, familial
      risk factors for AN. In terms of prevention, a particular attention should be
      paid to mothers with a lifetime history of psychiatric disorders.

PMID- 21193996
TI  - Arabidopsis thaliana transcriptional co-activators ADA2b and SGF29a are
      implicated in salt stress responses.
AB  - The transcriptional co-activator ADA2b is a component of GCN5-containing
      complexes in eukaryotes. In Arabidopsis, ada2b mutants result in pleiotropic
      developmental defects and altered responses to low-temperature stress. SGF29 has
      recently been identified as another component of GCN5-containing complexes. In
      the Arabidopsis genome there are two orthologs of yeast SGF29, designated as
      SGF29a and SGF29b. We hypothesized that, in Arabidopsis, one or both SGF29
      proteins may work in concert with ADA2b to regulate genes in response to abiotic
      stress, and we set out to explore the role of SGF29a and ADA2b in salt stress
      responses. In root growth and seed germination assays, sgf29a-1 mutants were more
      resistant to salt stress than their wild-type counterparts, whereas ada2b-1
      mutant was hypersensitive. The sgf29a;ada2b double mutant displayed similar
      phenotypes to ada2b-1 mutant with reduced salt sensitivity. The expression of
      several abiotic stress-responsive genes was reduced in ada2b-1 mutants after 3 h
      of salt stress in comparison with sgf29a-1 and wild-type plants. In the sgf29a
      1;ada2b-1 double mutant, the salt-induced gene expression was affected similarly
      to ada2b-1. These results suggest that under salt stress the function of SGF29a
      was masked by ADA2b and perhaps SGF29a could play an auxiliary role to ADA2b
      action. In chromatin immunoprecipitation assays, reduced levels of histone H3 and
      H4 acetylation in the promoter and coding region of COR6.6, RAB18, and RD29b
      genes were observed in ada2b-1 mutants relative to wild-type plants. In
      conclusion, ADA2b positively regulates salt-induced gene expression by
      maintaining the locus-specific acetylation of histones H4 and H3.

PMID- 21193997
TI  - Efficient virotherapy for osteosarcoma by telomerase-specific oncolytic
      adenovirus.
AB  - PURPOSE: A telomerase-specific oncolytic adenovirus, Telomelysin, can selectively
      kill cancer cells, and be attenuated in normal cells. We herein describe the
      oncolytic effect of Telomelysin on human osteosarcoma both in vitro and in vivo.
      METHODS: The anti-tumor effects of Telomelysin were evaluated on human
      osteosarcoma cell lines in vitro and in a mouse xenograft model of human
      osteosarcoma in vivo. The replication efficiencies of Telomelysin in human
      osteosarcoma cell lines and normal cell lines and in osteosarcoma xenografts were
      determined by the expression levels of E1 mRNA and E1A protein using real-time
      quantitative PCR, Western blot analysis and immunohistochemistry. The in vitro
      telomerase-specific replication and the viral infection rate were also confirmed
      by TelomeScan (Telomelysin-GFP), using fluorescent microscopy and flow cytometry,
      respectively. The cell viabilities were examined by XTT assay, and the tumor
      volumes were measured every 2 days. The induction of apoptosis was assessed by
      Western blot analysis, as well as by TUNEL assay. RESULTS: TelomeScan and
      Telomelysin were efficiently replicated in human osteosarcoma cell lines and led
      to a dose- and time-dependent expression of GFP, E1 mRNA and E1A protein.
      Telomelysin infection induced marked cytolysis and apoptosis in osteosarcoma cell
      lines in vitro. Neither cytotoxicity nor apoptosis were induced in normal human
      cell lines. In the human osteosarcoma cell xenograft model, intratumoral
      injection of Telomelysin resulted in increased viral replication, significant
      tumor growth suppression and distinct apoptotic cell death. CONCLUSIONS: This
      study indicated that virotherapy with Telomelysin may provide a promising
      strategy for the treatment of human osteosarcoma.

PMID- 21193998
TI  - Serum biomarkers for improved diagnostic of pancreatic cancer: a current
      overview.
AB  - PURPOSE: Complete resection constitutes the only curative approach in pancreatic
      cancer but is possible only in a minority of patients due to advanced stages upon
      diagnosis. Consequently, early detection is crucial for curative treatment.
      Clinical routine still lacks efficient, non-invasive screening assays, and 80-90%
      of pancreatic carcinomas are detected at unresectable stages. A wide range of
      serum proteins have been in the focus of intensive search for biomarkers specific
      for pancreatic cancer. This article will give an overview on serum biomarkers
      with screening potential for pancreatic malignancy. DESIGN AND METHODS: PUBMED
      database was searched for articles, and 43 manuscripts were selected that
      provided data regarding biomarkers used, type of assay, study population, sample
      cohort quality and diagnostic performance. RESULTS: Superior values for
      diagnostic performance were shown for MIC-1, PAM4, OPN, HSP27, TPS, TSGF, and
      CAM17.1 as individual markers. Panels of biomarkers comprised CA 19-9, MCSF, CEA,
      SAA, Haptoglobin, TSGF, CA 242, and HSP27. Individually or in concerted form,
      sensitivity and specificity ranged from 77 to 100% and 84-100%, respectively.
      CONCLUSIONS: While the above named markers show high screening potential for
      pancreatic cancer, standardized validation studies using multiplex assays are
      required to pave the way for clinical routine application.

PMID- 21193999
TI  - The effect of body mass index on the spread of spinal block in patients with
      rheumatoid arthritis.
AB  - PURPOSE: Body mass index (BMI) has a significant effect on the spread of sensory
      spinal block in rheumatoid patients. We tried to achieve the same spread of
      spinal block for patients in three different BMI groups and, on the basis of the
      results from a preliminary study, used a simple method feasible for clinical
      practice. We hypothesized that BMI-related inverse dosing of plain bupivacaine
      according to low, normal, and high BMI would result in no difference in block
      extent. METHODS: Together 75 patients with seropositive rheumatoid arthritis were
      included in three equal-sized groups according to BMI: low (<23 kg/m(2)), normal
      (23-28 kg/m(2)), and high (>28 kg/m(2)). Spinal anesthesia was induced with plain
      bupivacaine using doses 3.3, 3.0, and 2.7 ml, respectively. The spread of sensory
      block was recorded 30 min after injection of bupivacaine by use of a pin-prick
      test and a cold ice-filled container. RESULTS: Spreads of sensory block were
      different in low, normal, and high BMI groups (mean (SD); 14.0 (2.6), 14.5 (2.5),
      and 16.3 (2.5) dermatomes, respectively, P = 0.006) because of greater block
      extent in the high-BMI group. CONCLUSIONS: Despite three-step dosing of plain
      bupivacaine inversely related to BMI (low, normal, or high), comparable block
      extent was not achieved because of greater spread in the high-BMI group.
      Adjustment of plain bupivacaine dose according to BMI could be used to achieve a
      more predictable spread of spinal block, but further reduction of dose is needed
      in patients with high BMI.

PMID- 21194000
TI  - A novel association of alveolar capillary dysplasia, atypical duodenal atresia,
      and subglottic stenosis.
AB  - Alveolar capillary dysplasia (ACD), which is a rare and lethal congenital
      pulmonary anomaly found in newborns, begins its onset or causes deterioration of
      the infant's condition some time after birth. Various congenital anomalies in
      combination with ACD have been reported, except for subglottic stenosis.
      Therefore, we aim to report a novel association in a case of ACD with the
      combination of atypical duodenal atresia and subglottic stenosis. The male infant
      was scheduled for duodeno-duodenostomy because a double-bubble sign was observed
      on a chest radiograph. He arrived at the operating theater without any symptoms.
      After induction of general anesthesia, although mask ventilation was performed
      without difficulties throughout the entire procedure, oxygen saturation values of
      the upper and lower extremities dissociated after several attempts of intubation.
      Surgery was canceled because of instability of the respiratory condition.
      Respiratory insufficiency worsened progressively, and the infant died at 5 days
      of age. An autopsy confirmed ACD and revealed cartilaginous subglottic stenosis,
      which had made intubation difficult. This report highlights the hazards of the
      onset and worsening of ACD, and the importance of thorough echocardiography
      before surgery when atypical duodenal atresia is suspected. Anesthesiologists
      should also be prepared for the difficulty of intubation.

PMID- 21194001
TI  - Neuroprotective effects of a novel kynurenic acid analogue in a transgenic mouse
      model of Huntington's disease.
AB  - Huntington's disease (HD) is a progressive neurodegenerative disorder, the
      pathomechanism of which is not yet fully understood. Excitotoxicity is known to
      be involved in the development of HD and antiglutamatergic agents may, therefore,
      have beneficial neuroprotective effects. One of these agents is the tryptophan
      metabolite kynurenic acid (KYNA), which is an endogenous NMDA receptor
      antagonist. However, its pharmacological properties rule out its systemic
      administration in CNS disorders. We have tested a novel KYNA analogue, N-(2-N,N
      dimethylaminoethyl)-4-oxo-1H-quinoline-2-carboxamide hydrochloride, in the N171
      82Q transgenic mouse model of HD. The analogue exhibited several significant
      effects: it prolonged the survival of the transgenic mice, ameliorated their
      hypolocomotion, prevented the loss of weight and completely prevented the atrophy
      of the striatal neurons. The beneficial effects of this KYNA analogue are
      probably explained by its complex anti-excitotoxic activity. As it did not induce
      any appreciable side-effect at the protective dose applied in a chronic dosing
      regime in this mouse model, it appears worthy of further thorough investigations
      with a view to eventual clinical trials.

PMID- 21194002
TI  - The pedunculopontine nucleus as a target for deep brain stimulation.
AB  - The pedunculopontine nucleus (PPN) is a brain stem locomotive center that is also
      involved in the processing of sensory and behavioral information. The PPN has
      been recently proposed as a potential target for the treatment of axial symptoms
      in Parkinson's disease (PD). To date, results of the first series of PD patients
      treated with PPN deep brain stimulation (DBS) have shown promising results. In
      this article, we review some of the basic aspects of the PPN as a target and the
      outcome of the recently published clinical trials.

PMID- 21194004
TI  - Inflammation research: modern design, more quality science.

PMID- 21194003
TI  - Clostridium difficile infection in an endemic setting in the Netherlands.
AB  - The purpose of this investigation was to study risk factors for Clostridium
      difficile infection (CDI) in an endemic setting. In a 34-month prospective case
      control study, we compared the risk factors and clinical characteristics of all
      consecutively diagnosed hospitalised CDI patients (n = 93) with those of patients
      without diarrhoea (n = 76) and patients with non-CDI diarrhoea (n = 64). The
      incidence of CDI was 17.5 per 10,000 hospital admissions. C. difficile polymerase
      chain reaction (PCR) ribotype 014 was the most frequently found type (15.9%),
      followed by types 078 (12.7%) and 015 (7.9%). Independent risk factors for
      endemic CDI were the use of second-generation cephalosporins, previous hospital
      admission and previous stay at the intensive care unit (ICU). The use of third
      generation cephalosporins was a risk factor for diarrhoea in general. We found no
      association of CDI with the use of fluoroquinolones or proton pump inhibitors
      (PPIs). The overall 30-day mortality among CDI patients, patients without
      diarrhoea and patients with non-CDI diarrhoea was 7.5%, 0% and 1.6%,
      respectively. In this endemic setting, risk factors for CDI differed from those
      in outbreak situations. Some risk factors that have been ascribed to CDI earlier
      were, in this study, not specific for CDI, but for diarrhoea in general. The 30
      day mortality among CDI patients was relatively high.

PMID- 21194005
TI  - Optical coherence tomographic assessment of dynamic macular changes in patients
      with Vogt-Koyanagi-Harada disease.
AB  - To determine the relationship between visual acuity and three-dimensional optical
      coherence tomographic (3D-OCT) findings of the macula in eyes with Vogt-Koyanagi
      Harada (VKH) disease. Twelve eyes of six patients (three men and three woman,
      average age 53.2 years) in the acute phase of VKH disease were examined with a 3D
      OCT instrument. All of the eyes had a serous macular detachment. The height of
      the sensory retinal detachment (SRD) and the sensory retinal thickness (SRT) were
      measured by OCT before treatment (acute stage) and at the convalescent stage. The
      correlation between the retinal morphology and visual acuity was evaluated. The
      height of the SRD and the SRT were 612.5 +/- 371.2 and 136. 7 +/- 22.0 MUm,
      respectively. The initial visual acuity was significantly worse in eyes with a
      higher SRD (P = 0.014, r = 0.68) but the correlation between initial visual
      acuity and SRT was not significant. The recovery of visual acuity was attained in
      50.7 +/- 44.1 days and the complete resolution of the SRD was attained in 30.5 +/
      23.2 days. The final visual acuity was attained several days after the complete
      resolution of the SRD in all four eyes of patients over 60 years of age, but the
      recovery of visual acuity often preceded the complete resolution of the SRD. The
      OCT images provided a noninvasive indicator of the severity of the disease and
      dynamic changes in the macular morphology, reflecting the effect of treatment in
      association with the improvement in visual acuity. Monitoring the SRD by 3D-OCT
      may guide the tapering of systemic corticosteroid treatment.

PMID- 21194006
TI  - Laser photocoagulation (810 nm diode) for threshold retinopathy of prematurity: a
      prospective randomized pilot study of treatment to ridge and avascular retina
      versus avascular retina alone.
AB  - The purpose of this study was to compare the structural outcome of laser
      treatment to avascular retina and ridge versus laser treatment to avascular
      retina alone in cases with threshold retinopathy of prematurity (ROP). A
      prospective, randomized, interventional, comparative study of consecutive cases
      referred to a single tertiary center was considered here. 50 infants with
      bilateral symmetrical threshold ROP were recruited into this study over a period
      of 3 years. Threshold ROP was defined as per CRYO-ROP study. Perinatal history
      details for all patients including significant maternal history were recorded.
      One eye of each patient was randomized (Microsoft Excel 2000) to one of the two
      treatment groups--laser treatment to avascular retina (Group A) or laser
      treatment to avascular retina and ridge (Group B). Laser treatment was performed
      with a 810 nm diode laser (Iris Medical Instruments, Inc. Mountain View, CA,
      USA). Treatment was continued until regression of ROP. Structural outcome was
      assessed at a minimum follow-up of 6 months and was considered favorable or
      unfavorable as per the CRYO-ROP study criteria. An unfavorable outcome consisted
      of either (1) a retinal fold involving the macula; (2) any retinal detachment
      involving zone 1; or (3) a retrolental mass that obscured visualization of the
      posterior pole. Secondary outcome measures included the difference in time to
      regression of ROP and complications of treatment between the two treatment
      groups. 100 eyes of 50 infants received laser photocoagulation for threshold ROP
      after randomization (50 eyes in each group). Of these 50 infants, 20 (40%) were
      female and 30 (60%) were male. A significant proportion of the children (46%)
      were conceived as twins. The average birth weight was 1360 +/- 326 g (range 750
      2200 g). The mean gestational age at birth was 30.72 +/- 1.6 weeks (range 26-36
      weeks). Zone I disease was present in 14 (14%) eyes and zone II in the remaining
      86 eyes (86%). Threshold stage retinopathy (CRYO-ROP criteria) extending 360
      degrees  (12 clock hours) was present in 21 infants (42%), 5 contiguous clock
      hours of stage 3+ in 14 infants (28%) and intermediate range in the remaining 15
      infants (30%). At 6 months follow-up, 3 eyes (6%) in group A and 1 eye (2%) in
      group B had an adverse structural outcome; however, the time to regression of
      retinopathy 2.98 +/- 1.5 weeks in group A and 3.12 +/- 1.1 in group B (P = 0.889)
      and the rate of complications such as retinal hemorrhage, 3 eyes in group A and 4
      eyes in group B, was comparable. Zone I eyes showed equal incidence of favorable
      anatomical outcome (85.7%) in each group. Laser treatment to ridge was found to
      be safe and effective in the treatment of threshold ROP in this short-term pilot
      study; however, it needs to be ascertained whether this treatment has long-term
      advantages over conventional laser treatment to avascular retina, as well as the
      long-term benefits of treatment to ridge.

PMID- 21194007
TI  - A systems view of epithelial-mesenchymal transition signaling states.
AB  - Epithelial-mesenchymal transition (EMT) is an important contributor to the
      invasion and metastasis of epithelial-derived cancers. While considerable effort
      has focused in the regulators involved in the transition process, we have focused
      on consequences of EMT to prosurvival signaling. Changes in distinct metastable
      and 'epigentically-fixed' EMT states were measured by correlation of protein,
      phosphoprotein, phosphopeptide and RNA transcript abundance. The assembly of 1167
      modulated components into functional systems or machines simplified biological
      understanding and increased prediction confidence highlighting four functional
      groups: cell adhesion and migration, metabolism, transcription nodes and
      proliferation/survival networks. A coordinate metabolic reduction in a cluster of
      17 free-radical stress pathway components was observed and correlated with
      reduced glycolytic and increased oxidative phosphorylation enzyme capacity,
      consistent with reduced cell cycling and reduced need for macromolecular
      biosynthesis in the mesenchymal state. An attenuation of EGFR autophosphorylation
      and a switch from autocrine to paracrine-competent EGFR signaling was implicated
      in the enablement of tumor cell chemotaxis. A similar attenuation of IGF1R, MET
      and RON signaling with EMT was observed. In contrast, EMT increased prosurvival
      autocrine IL11/IL6-JAK2-STAT signaling, autocrine fibronectin-integrin
      alpha5beta1 activation, autocrine Axl/Tyro3/PDGFR/FGFR RTK signaling and
      autocrine TGFbetaR signaling. A relatively uniform loss of polarity and cell-cell
      junction linkages to actin cytoskeleton and intermediate filaments was measured
      at a systems level. A more heterogeneous gain of ECM remodeling and associated
      with invasion and migration was observed. Correlation to stem cell, EMT, invasion
      and metastasis datasets revealed the greatest similarity with normal and
      cancerous breast stem cell populations, CD49f(hi)/EpCAM(-/lo) and
      CD44(hi)/CD24(lo), respectively.

PMID- 21194009
TI  - Mitosis in vertebrates: the G2/M and M/A transitions and their associated
      checkpoints.
AB  - In this review, I stress the importance of direct data and accurate terminology
      when formulating and communicating conclusions on how the G2/M and
      metaphase/anaphase transitions are regulated. I argue that entry into mitosis
      (i.e., the G2/M transition) is guarded by several checkpoint control pathways
      that lose their ability to delay or stop further cell cycle progression once the
      cell becomes committed to divide, which in vertebrates occurs in the late stages
      of chromosome condensation. After this commitment, progress through mitosis is
      then mediated by a single Mad/Bub-based checkpoint that delays chromatid
      separation, and exit from mitosis (i.e., completion of the cell cycle) in the
      presence of unattached kinetochores. When cells cannot satisfy the mitotic
      checkpoint, e.g., when in concentrations of spindle poisons that prohibit the
      stable attachment of all kinetochores, they are delayed in mitosis for many
      hours. In normal cells, the duration of this delay depends on the organism and
      ranges from ~4 h in rodents to ~22 h in humans. Recent live cell studies reveal
      that under this condition, many cancer cells (including HeLa and U2OS) die in
      mitosis by apoptosis within ~24 h, which implies that biochemical studies on
      cancer cell populations harvested in mitosis after a prolonged mitotic arrest are
      contaminated with dead or dying cells.

PMID- 21194010
TI  - Iron exposure modifies acetylcholinesterase activity in zebrafish (Danio rerio)
      tissues: distinct susceptibility of tissues to iron overload.
AB  - Iron is one the most abundant metals on the earth being essential for living
      organisms even though its free form can be toxic. The overload of this metal may
      be related with some disorders, like Alzheimer and Parkinson diseases, and
      hemochromatosis in the liver. The aim of the present study was to evaluate the
      effects of iron on acetylcholinesterase (AChE) activity in brain and liver of
      zebrafish and to investigate the possible correlation with the iron content in
      these tissues. Different corresponding concentrations of iron were tested using
      in vitro (0.018, 0.268, and 2.6 mM) and in vivo (1, 15, and 150 mg/l) assays. The
      in vitro studies showed that iron promoted a significant increase in AChE
      activity in brain (52%) and liver (53%) at the higher concentration (2.6 mM). In
      the in vivo assays, a significant increase in this enzyme activity was observed
      in the presence of 15 mg/l in both, brain (62%) and liver tissue (70%).
      Semiquantitative RT-PCR did not reveal significant changes in
      acetylthiocholinesterase mRNA levels. Moreover, we observed that iron content was
      significantly increased in liver tissue when exposed to 15 (226%) and 150 mg/l
      (200%). These results indicate that iron can promote significant alterations in
      AChE activity which probably is not directly related to the iron content in
      zebrafish tissues.

PMID- 21194011
TI  - Social networking technology, social network composition, and reductions in
      substance use among homeless adolescents.
AB  - Peer-based prevention programs for homeless youth are complicated by the
      potential for reinforcing high-risk behaviors among participants. The goal of
      this study is to understand how homeless youth could be linked to positive peers
      in prevention programming by understanding where in social and physical space
      positive peers for homeless youth are located, how these ties are associated with
      substance use, and the role of social networking technologies (e.g., internet and
      cell phones) in this process. Personal social network data were collected from
      136 homeless adolescents in Los Angeles, CA. Respondents reported on composition
      of their social networks with respect to: home-based peers and parents (accessed
      via social networking technology; e.g., the internet, cell phone, texting),
      homeless peers and agency staff (accessed face-to-face) and whether or not
      network members were substance-using or non-substance-using. Associations between
      respondent's lifetime cocaine, heroin, and methamphetamine use and recent
      (previous 30 days) alcohol and marijuana use were assessed by the number of non
      substance-using versus substance-using ties in multivariate linear regression
      models. 43% of adolescents reported a non-substance-using home-based tie. More of
      these ties were associated with less recent alcohol use. 62% of adolescents
      reported a substance-using homeless tie. More of these ties were associated with
      more recent marijuana use as well as more lifetime heroin and methamphetamine
      use. For homeless youth, who are physically disconnected from positive peers,
      social networking technologies can be used to facilitate the sorts of positive
      social ties that effective peer-based prevention programs require.

PMID- 21194012
TI  - Homogenization of large-scale movement models in ecology.
AB  - A difficulty in using diffusion models to predict large scale animal population
      dispersal is that individuals move differently based on local information (as
      opposed to gradients) in differing habitat types. This can be accommodated by
      using ecological diffusion. However, real environments are often spatially
      complex, limiting application of a direct approach. Homogenization for partial
      differential equations has long been applied to Fickian diffusion (in which
      average individual movement is organized along gradients of habitat and
      population density). We derive a homogenization procedure for ecological
      diffusion and apply it to a simple model for chronic wasting disease in mule
      deer. Homogenization allows us to determine the impact of small scale (10-100 m)
      habitat variability on large scale (10-100 km) movement. The procedure generates
      asymptotic equations for solutions on the large scale with parameters defined by
      small-scale variation. The simplicity of this homogenization procedure is
      striking when compared to the multi-dimensional homogenization procedure for
      Fickian diffusion,and the method will be equally straightforward for more complex
      models.

PMID- 21194013
TI  - Pectin matrix as oral drug delivery vehicle for colon cancer treatment.
AB  - Colon cancer is the fourth most common cancer globally with 639,000 deaths
      reported annually. Typical chemotherapy is provided by injection route to reduce
      tumor growth and metastasis. Recent research investigates the oral delivery
      profiles of chemotherapeutic agents. In comparison to injection, oral
      administration of drugs in the form of a colon-specific delivery system is
      expected to increase drug bioavailability at target site, reduce drug dose and
      systemic adverse effects. Pectin is suitable for use as colon-specific drug
      delivery vehicle as it is selectively digested by colonic microflora to release
      drug with minimal degradation in upper gastrointestinal tract. The present review
      examines the physicochemical attributes of formulation needed to retard drug
      release of pectin matrix prior to its arrival at colon, and evaluate the
      therapeutic value of pectin matrix in association with colon cancer. The review
      suggests that multi-particulate calcium pectinate matrix is an ideal carrier to
      orally deliver drugs for site-specific treatment of colon cancer as (1)
      crosslinking of pectin by calcium ions in a matrix negates drug release in upper
      gastrointestinal tract, (2) multi-particulate carrier has a slower transit and a
      higher contact time for drug action in colon than single-unit dosage form, and
      (3) both pectin and calcium have an indication to reduce the severity of colon
      cancer from the implication of diet and molecular biology studies. Pectin matrix
      demonstrates dual advantages as drug carrier and therapeutic for use in treatment
      of colon cancer.

PMID- 21194014
TI  - Development and evaluation of chitosan-coated liposomes for oral DNA vaccine: the
      improvement of Peyer's patch targeting using a polyplex-loaded liposomes.
AB  - The aim of this study was to develop chitosan-coated and polyplex-loaded
      liposomes (PLLs) containing DNA vaccine for Peyer's patch targeting. Plain
      liposomes carrying plasmid pRc/CMV-HBs were prepared by the reverse-phase
      evaporation method. Chitosan coating was carried out by incubation of the
      liposomal suspensions with chitosan solution. Main lipid components of liposomes
      were phosphatidylcholine/cholesterol. Sodium deoxycholate and dicetyl phosphate
      were used as negative charge inducers. The zeta potentials of plain liposomes
      were strongly affected by the pH of the medium. Coating with chitosan variably
      increased the surface charges of the liposomes. To increase the zeta potential
      and stability of the liposome, chitosan was also used as a DNA condensing agent
      to form a polyplex. The PLLs were coated with chitosan solution. In vivo study of
      PLLs was carried out in comparison with chitosan-coated liposomes using plasmid
      encoding green fluorescence protein as a reporter. A single dose of plasmid equal
      to 100 MUg was intragastrically inoculated into BALB/c mice. The expression of
      green fluorescence protein (GFP) was detected after 24 h using a confocal laser
      scanning microscope. The signal of GFP was obtained from positively charged
      chitosan-coated liposomes but found only at the upper part of duodenum. With
      chitosan-coated PLL540, the signal of GFP was found throughout the intestine.
      Chitosan-coated PLL demonstrated a higher potential to deliver the DNA to the
      distal intestine than the chitosan-coated liposomes due to the increase in
      permanent positive surface charges and the decreased enzymatic degradation.

PMID- 21194015
TI  - The clock drawing test is a poor screening tool for postoperative delirium and
      cognitive dysfunction after aortic repair.
AB  - BACKGROUND: The Clock Drawing Test (CDT) is a screening tool for dementia that
      tests a variety of cognitive domains. The CDT takes a maximum of two minutes to
      complete and might be helpful in identifying postoperative cognitive disorders at
      the bedside. The objective of this study was to evaluate the accuracy of the CDT
      in a population at high risk for postoperative cognitive disorders METHODS: In
      this prospective observational cohort study, patients were recruited who were >=
      60 yr of age and scheduled for elective open repair of the abdominal aorta.
      Delirium was assessed using the Confusion Assessment Method (CAM) on
      postoperative days (POD) 2 and 4 and at discharge. Cognitive function was
      assessed with neuropsychometric tests before surgery and at discharge.
      Postoperative cognitive dysfunction (POCD) was determined using the Reliable
      Change Index. Clock Drawing Tests were administered at all time points. Agreement
      between the CDT and test for delirium or POCD was assessed with Cohen's Kappa
      statistic. RESULTS: Delirium was noted in 30 of 83 patients (36%; 95% confidence
      interval [CI] 26 to 46%) during their hospital stay, while POCD was noted in 48
      of 78 patients (60%; 95% CI 51 to 72%) at discharge. Agreement between the CDT
      and CAM was poor at three intervals (Kappa 0.06 to 0.29), as was POCD at
      discharge (Kappa 0.46). Sensitivity of the CDT was <0.71 for both delirium and
      POCD at all intervals. False positives and negatives were common. CONCLUSION:
      Agreement between CDT and tests for delirium and POCD was poor; sensitivity was
      inadequate for a screening test. (ClinicalTrials.gov number, NCT00911677).

PMID- 21194016
TI  - The how and why of "negative" research studies.

PMID- 21194018
TI  - Design and testing of regulatory cassettes for optimal activity in skeletal and
      cardiac muscles.
AB  - Gene therapy for muscular dystrophies requires efficient gene delivery to the
      striated musculature and specific, high-level expression of the therapeutic gene
      in a physiologically diverse array of muscles. This can be achieved by the use of
      recombinant adeno-associated virus vectors in conjunction with muscle-specific
      regulatory cassettes. We have constructed several generations of regulatory
      cassettes based on the enhancer and promoter of the muscle creatine kinase gene,
      some of which include heterologous enhancers and individual elements from other
      muscle genes. Since the relative importance of many control elements varies among
      different anatomical muscles, we are aiming to tailor these cassettes for high
      level expression in cardiac muscle, and in fast and slow skeletal muscles. With
      the achievement of efficient intravascular gene delivery to isolated limbs,
      selected muscle groups, and heart in large animal models, the design of cassettes
      optimized for activity in different muscle types is now a practical goal. In this
      protocol, we outline the key steps involved in the design of regulatory cassettes
      for optimal activity in skeletal and cardiac muscle, and testing in mature muscle
      fiber cultures. The basic principles described here can also be applied to
      engineering tissue-specific regulatory cassettes for other cell types.

PMID- 21194017
TI  - GABA(A) receptors as molecular targets of general anesthetics: identification of
      binding sites provides clues to allosteric modulation.
AB  - PURPOSE: The purpose of this review is to summarize current knowledge of detailed
      biochemical evidence for the role of gamma-aminobutyric acid type A receptors
      (GABA(A)-Rs) in the mechanisms of general anesthesia. PRINCIPAL FINDINGS: With
      the knowledge that all general anesthetics positively modulate GABA(A)-R-mediated
      inhibitory transmission, site-directed mutagenesis comparing sequences of GABA(A)
      R subunits of varying sensitivity led to identification of amino acid residues in
      the transmembrane domain that are critical for the drug actions in vitro. Using a
      photo incorporable analogue of the general anesthetic, R(+)etomidate, we
      identified two transmembrane amino acids that were affinity labelled in purified
      bovine brain GABA(A)-R. Homology protein structural modelling positions these two
      residues, alphaM1-11' and betaM3-4', close to each other in a single type of
      intersubunit etomidate binding pocket at the beta/alpha interface. This position
      would be appropriate for modulation of agonist channel gating. Overall, available
      information suggests that these two etomidate binding residues are allosterically
      coupled to sites of action of steroids, barbiturates, volatile agents, and
      propofol, but not alcohols. Residue alpha/betaM2-15' is probably not a binding
      site but allosterically coupled to action of volatile agents, alcohols, and
      intravenous agents, and alpha/betaM1-(-2') is coupled to action of intravenous
      agents. CONCLUSIONS: Establishment of a coherent and consistent structural model
      of the GABA(A)-R lends support to the conclusion that general anesthetics can
      modulate function by binding to appropriate domains on the protein. Genetic
      engineering of mice with mutation in some of these GABA(A)-R residues are
      insensitive to general anesthetics in vivo, suggesting that further analysis of
      these domains could lead to development of more potent and specific drugs.

PMID- 21194019
TI  - Codon optimization of the microdystrophin gene for Duchene muscular dystrophy
      gene therapy.
AB  - Duchenne muscular dystrophy (DMD) is a severe muscle wasting X-linked genetic
      disease caused by dystrophin gene mutations. Gene replacement therapy aims to
      transfer a functional full-length dystrophin cDNA or a quasi micro/mini-gene into
      the muscle. A number of AAV vectors carrying microdystrophin genes have been
      tested in the mdx model of DMD. Further modification/optimization of these
      microgene vectors may improve the therapeutic potency. In this chapter, we
      describe a species-specific, codon optimization protocol to improve
      microdystrophin gene therapy in the mdx model.

PMID- 21194020
TI  - Monitoring duchenne muscular dystrophy gene therapy with epitope-specific
      monoclonal antibodies.
AB  - Several molecular approaches to Duchenne muscular dystrophy (DMD) therapy are at
      or near the point of clinical trial and usually involve attempts to replace the
      missing dystrophin protein. Although improved muscle function is the ultimate
      measure of success, assessment of dystrophin levels after therapy is essential to
      determine whether any improved function is a direct consequence of the treatment
      or, in the absence of improved function, to determine whether new dystrophin is
      present, though ineffective. The choice of a monoclonal antibody (mAb) to
      distinguish successful therapy from naturally occurring "revertant" fibres
      depends on which dystrophin exons are deleted in the DMD patient. Over the past
      20 years, we have produced over 150 "exon-specific" mAbs, mapped them to
      different regions of dystrophin and made them available through the MDA
      Monoclonal Antibody Resource for research and for clinical trials tailored to
      individual patients. In this protocol, we describe the use of these mAb to
      monitor DMD gene therapy.

PMID- 21194021
TI  - Methods for noninvasive monitoring of muscle fiber survival with an AAV vector
      encoding the mSEAP reporter gene.
AB  - Muscular dystrophies (MD) are a group of genetically and phenotypically
      heterogeneous inherited disorders characterized by the progressive degeneration
      of the skeletal muscle tissue. In the last decade, a tremendous amount of studies
      were performed to test therapeutic strategies in animal models. Evaluation of
      such strategies requires the use of criteria predictive of their therapeutic
      relevance. Here we describe a simple, noninvasive assay to monitor muscle
      degenerative process. An adeno-associated vector encoding a secreted form of
      murine embryonic alkaline phosphatase (mSEAP) reporter gene is administrated at
      the time of treatment. The amount of circulating mSEAP will reflect the level of
      myofiber survival. We tested this assay with therapeutic gene transfer. We found
      a strong correlation between therapeutic gene expression/muscle disease
      amelioration and the circulating levels of mSEAP. The assay will be very useful
      for monitoring muscle cell survival after therapeutic intervention.

PMID- 21194022
TI  - Monitoring murine skeletal muscle function for muscle gene therapy.
AB  - The primary function of skeletal muscle is to generate force. Muscle force
      production is compromised in various forms of acquired and/or inherited muscle
      diseases. An important goal of muscle gene therapy is to recover muscle strength.
      Genetically engineered mice and spontaneous mouse mutants are readily available
      for preclinical muscle gene therapy studies. In this chapter, we outlined the
      methods commonly used for measuring murine skeletal muscle function. These
      include ex vivo and in situ analysis of the contractile profile of a single
      intact limb muscle (the extensor digitorium longus for ex vivo assay and the
      tibialis anterior muscle for in situ assay), grip force analysis, and downhill
      treadmill exercise. Force measurement in a single muscle is extremely useful for
      pilot testing of new gene therapy protocols by local gene transfer. Grip force
      and treadmill assessments offer body-wide evaluation following systemic muscle
      gene therapy.

PMID- 21194023
TI  - Phenotyping cardiac gene therapy in mice.
AB  - Heart disease is the leading health problem of industrialized countries. The
      development of gene therapies tailored towards the heart has grown exponentially
      over the past decade. Murine models of heart diseases have played a pivotal role
      in testing novel cardiac gene therapy approaches. Unfortunately, the small body
      size and rapid heart rate of mice present a great challenge to heart function
      evaluation. Here we outline the commonly used cardiac phenotyping methods of
      treadmill exercise regimen, full 12-lead electrocardiographic assay and left
      ventricular catheterization hemodynamic assay. Application of these protocols
      will allow critical testing of gene therapy efficacy in mouse models of heart
      diseases.

PMID- 21194024
TI  - Golden retriever muscular dystrophy (GRMD): Developing and maintaining a colony
      and physiological functional measurements.
AB  - Studies of canine models of Duchenne muscular dystrophy (DMD) provide insight
      regarding disease pathogenesis and treatment efficacy. To take maximal advantage,
      colonies of affected dogs must be maintained and outcome parameters developed. In
      this chapter, we review our 25 years of experience with the golden retriever
      muscular dystrophy (GRMD) model. Key challenges in colony development (breeding,
      neonatal death, and the risk of inbreeding) and representative functional
      measurements (tibiotarsal joint angle and torque force; and eccentric contraction
      decrement) are discussed.

PMID- 21194025
TI  - Directed evolution of adeno-associated virus (AAV) as vector for muscle gene
      therapy.
AB  - Adeno-associated virus (AAV) is emerging as a vector of choice for muscle gene
      therapy because of its effective and stable transduction in striated muscles. AAV
      naturally evolve into multiple serotypes with diverse capsid gene sequences that
      are apparently the determinants of their tissue tropism and infectivity. Certain
      AAV serotypes show robust gene transfer upon direct intramuscular injection,
      while others are effective in crossing the endothelial barrier to reach muscle
      when delivered intravenously. Muscular dystrophy gene therapy requires efficient
      body-wide muscle gene transfer. However, preferential liver transduction by
      nearly all natural AAV serotypes could be an undesirable feature for muscle
      directed applications, especially by means of systemic gene delivery. Here we
      describe a method of in vitro evolution and in vivo selection of AAV capsids that
      target striated muscles and detarget the liver. Using DNA shuffling technology,
      we have generated a capsid gene library by in vitro scrambling and shuffling the
      capsid genes of natural AAV1 to AAV9. To minimize the bias and limitation of in
      vitro screening on culture cells, we performed direct in vivo panning in adult
      mice after intravenous injection of the shuffled capsid library that packaged
      their own coding sequences. The AAV variants enriched in the heart and muscle are
      retrieved by capsid gene PCR and subsequently characterized for their tissue
      tropisms. This directed evolution and in vivo selection method should be useful
      in generating novel gene therapy vectors for muscle and heart and other tissues.

PMID- 21194026
TI  - Systemic gene transfer to skeletal muscle using reengineered AAV vectors.
AB  - Gene therapy of musculoskeletal disorders warrants efficient gene transfer to a
      wide range of muscle groups. Reengineered adeno-associated viral (AAV) vectors
      that selectively transduce muscle tissue following systemic administration are
      attractive candidates for such applications. Here we provide examples of several
      lab-derived AAV vectors that display systemic tissue tropism in mice. Methods to
      evaluate the efficiency of gene transfer to skeletal muscle following intravenous
      or isolated limb infusion of AAV -vectors in mice are discussed in detail.

PMID- 21194027
TI  - Bioinformatic and functional optimization of antisense phosphorodiamidate
      morpholino oligomers (PMOs) for therapeutic modulation of RNA splicing in muscle.
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 (BMD)-like, but
      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 so that gene expression is restored. AO-induced exon skipping
      producing functional truncated dystrophin exon has been demonstrated in animal
      models of DMD both in vitro and in vivo, and in DMD patient cells in vitro in
      culture, and in DMD muscle explants. More recently, AO-mediated exon skipping has
      been confirmed in DMD patients in Phase I clinical trials. 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, and in
      particular phosphorodiamidate morpholino oligomers (PMOs), for the targeted
      skipping of specific exons on the DMD gene.

PMID- 21194028
TI  - Engineering exon-skipping vectors expressing U7 snRNA constructs for Duchenne
      muscular dystrophy gene therapy.
AB  - Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disorder caused by
      mutations in the dystrophin gene. In most cases, the open-reading frame is
      disrupted which results in the absence of a functional protein. Antisense
      mediated exon skipping is one of the most promising approaches for the treatment
      of DMD and has recently been shown to correct the reading frame and restore
      dystrophin expression in vitro and in vivo. Specific exon skipping can be
      achieved using synthetic oligonucleotides or viral -vectors encoding modified
      snRNAs, by masking important splicing sites. We have recently demonstrated that
      enhanced exon skipping can be induced by a U7 snRNA carrying binding sites for
      the heterogeneous ribonucleoprotein A1. In DMD patient cells, bifunctional U7
      snRNAs harboring silencer motifs induce complete skipping of exon 51 and thus
      restore dystrophin expression to near wild-type levels. Furthermore, we have
      confirmed the efficacy of these constructs in vivo in transgenic mice carrying
      the entire human DMD locus after intramuscular injection of AAV vectors encoding
      the bifunctional U7 snRNA. 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 U7 snRNA constructs to achieve efficient
      exon skipping of the dystrophin gene. We also describe methods to evaluate the
      efficiency of such U7 snRNA constructs in vitro in DMD patient cells and in vivo
      in the transgenic hDMD mouse model, using lentiviral and recombinant adeno
      associated viral vectors, respectively.

PMID- 21194029
TI  - Application of microRNA in cardiac and skeletal muscle disease gene therapy.
AB  - MicroRNAs (miRNAs) are a class of small ~22 nt noncoding RNAs. miRNAs regulate
      gene expression at the posttranscriptional levels by destabilization and
      degradation of the target mRNA or by translational repression. Numerous studies
      have demonstrated that miRNAs are essential for normal mammalian development and
      organ function. Deleterious changes in miRNA expression play an important role in
      human diseases. We and others have previously reported several muscle-specific
      miRNAs, including miR-1/206, miR-133, and miR-208. These muscle-specific miRNAs
      are essential for normal myoblast differentiation and proliferation, and they
      have also been implicated in various cardiac and skeletal muscular diseases.
      miRNA-based gene therapies hold great potential for the treatment of cardiac and
      skeletal muscle disease(s). Herein, we introduce the methods commonly applied to
      study the biological role of miRNAs, as well as the techniques utilized to
      manipulate miRNA expression.

PMID- 21194030
TI  - Molecular imaging of RNA interference therapy targeting PHD2 for treatment of
      myocardial ischemia.
AB  - Coronary artery disease is the number one cause of morbidity and mortality in the
      Western world. It typically occurs when heart muscle receives inadequate blood
      supply due to rupture of atherosclerotic plaques. During ischemia, up-regulation
      of hypoxia inducible factor-1 alpha (HIF-1alpha) transcriptional factor can
      activate several downstream angiogenic genes. However, HIF-1alpha is naturally
      degraded by prolyl hydroxylase-2 (PHD2) protein. Recently, we cloned the mouse
      PHD2 gene by comparing the homolog gene in human and rat. The best candidate
      shRNA sequence for inhibiting PHD2 was inserted behind H1 promoter, followed by a
      separate hypoxia response element (HRE)-incorporated promoter driving a firefly
      luciferase (Fluc) reporter gene. This construct allowed us to monitor gene
      expression noninvasively and was used to test the hypothesis that inhibition of
      PHD2 by short hairpin RNA interference (shRNA) can lead to significant
      improvement in angiogenesis and contractility as revealed by in vitro and in vivo
      experiments.

PMID- 21194031
TI  - Lentiviral vector delivery of shRNA into cultured primary myogenic cells: a tool
      for therapeutic target validation.
AB  - RNA interference has emerged as a powerful technique to down-regulate gene
      expression. The lentiviral vector-mediated expression of small hairpin RNAs
      (shRNAs) from polymerase III promoters allows permanent down-regulation of a
      specific gene in a wide range of cell types both in vitro and in vivo. In this
      chapter, we describe a method permitting the expression of shRNA from lentiviral
      vectors in primary murine myogenic cells. We designed shRNAs targeted to the
      muscular glycogen synthase isoform (shGYS1), a highly regulated enzyme
      responsible for glycogen synthesis, in order to modulate the muscle glycogen
      biosynthetic pathway and to improve the phenotype in primary myogenic cells from
      a murine model of glycogen storage disease type II (GSDII). This method based on
      shRNA-mediated down-regulation could be applied to other muscular disorders to
      evaluate new therapeutic options.

PMID- 21194032
TI  - Fetal muscle gene therapy/gene delivery in large animals.
AB  - Gene delivery to the fetal muscles is a potential strategy for the early
      treatment of muscular dystrophies. In utero muscle gene therapy can also be used
      to treat other genetic disorders such as hemophilia, where the missing clotting
      proteins may be secreted from the treated muscle. In the past few years, studies
      in small animal models have raised the hopes that a phenotypic cure can be
      obtained after fetal application of gene therapy. Studies of efficacy and safety
      in large animals are, however, essential before clinical application can be
      considered in the human fetus. For this reason, the development of clinically
      applicable strategies for the delivery of gene therapy to the fetal muscles is of
      prime importance. In this chapter, we describe the protocols for in utero
      ultrasound-guided gene delivery to the ovine fetal muscle in early gestation. In
      particular, procedures to inject skeletal muscle groups such as the thigh and
      thoracic musculature and targeting the diaphragm in the fetus are described in
      detail.

PMID- 21194033
TI  - Electroporation of plasmid DNA to swine muscle.
AB  - For plasmid-mediated gene therapy applications, a major limitation to scale up
      from rodents to large animals is the low expression level of injected plasmid
      DNA. The electroporation technique, which results in the passage of foreign
      material through the cell membrane, is one method that has been shown to be
      effective at improving local plasmid uptake and consequently, expression levels.
      Previous studies have determined that optimized electroporation parameters (such
      as electric field intensity, number of pulses, lag time between plasmid
      injections and electroporations, and optimal plasmid formulation conditions) are
      dependent on the target muscle type and individual species. Here, we provide a
      detailed protocol to optimize conditions for the successful intramuscular
      electroporation of plasmid DNA to swine, a large animal model. Our results
      suggest that the technique is safe and effective for veterinary applications.
      Furthermore, these results provide evidence for the feasibility of upcoming human
      applications.

PMID- 21194034
TI  - Local gene delivery and methods to control immune responses in muscles of normal
      and dystrophic dogs.
AB  - Adeno-associated viral vector (AAV)-mediated gene transfer represents a promising
      gene replacement strategy for treating Duchenne muscular dystrophy (DMD).
      However, recent studies demonstrated cellular immunity specific to AAV capsid
      proteins in animal models, which resulted in liver toxicity and elimination of
      transgene expression in a human trial of hemophilia B. We have recently developed
      immunosuppressive strategies to prevent such immunity for successful long-term
      transgene expression in dog muscle. Here, we describe in detail the
      immunosuppressive regimens employed in both normal and DMD dogs and provide
      methods for evaluating the efficiency of the regimens following intramuscular
      injection of AAV in dogs.

PMID- 21194035
TI  - Gene transfer to muscle from the isolated regional circulation.
AB  - Vector transport across the endothelium has long been regarded as one of the
      central "bottlenecks" in gene therapy research, especially as it pertains to the
      muscular dystrophies where the target tissue approaches half of the total body
      mass. Clinical studies of gene therapy for hemophilia B revealed the limitations
      of the intramuscular route, compelling an aggressive approach to the study of
      scale-independent circulatory means of vector delivery. The apparent permeability
      of the microvasculature in small animals suggests that gravitational and/or
      inertial effects on the circulation require progressive restriction of fluid and
      solute flow across the capillary wall with increasing body size. To overcome this
      physiological restriction, we initially used a combined surgical and
      pharmacological approach to temporarily alter permeability within the isolated
      pelvic limb. Although this was successful, new information about the cell and
      molecular biology of histamine-induced changes in microvascular permeability
      suggested an alternative approach, which substituted pressure-induced
      transvenular extravasation. Here we outline the details of our surgical
      approaches in the rat. We also discuss the modifications that are appropriate for
      the dog.

PMID- 21194036
TI  - AAV-mediated gene therapy to the isolated limb in rhesus macaques.
AB  - The development of a nonhuman primate (NHP) model for vascular delivery of
      therapeutic transgenes with adeno-associated viral (AAV) vectors is crucial for
      successfully treating muscular dystrophies. Current animal models for Duchenne
      muscular dystrophy (DMD) gene therapy have species limitations related to
      assessing function, immune response, and distribution of the micro- and
      minidystrophin transgenes in a clinically relevant manner. In addition, there are
      many forms of muscular dystrophy for which there are no available disease models.
      NHPs provide the ideal model to optimize vector delivery across a vascular
      barrier and provide accurate dose estimates for local or broadly targeted gene
      therapy studies. The vascular anatomy NHPs more clearly parallels humans
      providing an appropriate substrate for translational experiments. Here we outline
      the development of a rhesus macaque isolated focal limb perfusion (IFLP) protocol
      targeting the vascular bed of the gastrocnemius. This protocol serves as a model
      with broad implications for other muscle diseases along with the capability of
      targeting multiple muscle groups. To overcome the partial homogeneity between
      portions of the human microdystrophin transgene and those of the NHP dystrophin
      gene, we utilized a FLAG tag for tracking distribution of microdystrophin. We
      also provide methods for assessing transduction efficiency of
      microdystrophin.FLAG following the IFLP vascular delivery protocol.

PMID- 21194037
TI  - Antisense oligo-mediated multiple exon skipping in a dog model of duchenne
      muscular dystrophy.
AB  - Exon skipping is currently one of the most promising molecular therapies for
      Duchenne muscular -dystrophy (DMD). We have recently developed multiple exon
      skipping targeting exons 6 and 8 in -dystrophin mRNA of canine X-linked muscular
      dystrophy (CXMD), an animal model of DMD, which exhibits severe dystrophic
      phenotype in skeletal muscles and cardiac muscle. We have induced efficient exon
      skipping both in vitro and in vivo by using cocktail antisense 2'O-methyl
      oligonucleotides (2'OMePS) and cocktail phosphorodiamidate morpholino oligomers
      (morpholinos, or PMOs) and ameliorated phenotype of dystrophic dogs by systemic
      injections. The multiple exon skipping (double exon skipping) shown here provides
      the prospect of choosing deletions that optimize the functionality of the
      truncated dystrophin protein for DMD patients by using a common cocktail that
      could be validated as a single drug and also potentially applicable for more than
      90% of DMD patients.

PMID- 21194038
TI  - Whole body skeletal muscle transduction in neonatal dogs with AAV-9.
AB  - Gene therapy of muscular dystrophy requires systemic gene delivery to all muscles
      in the body. Adeno-associated viral (AAV) vectors have been shown to lead to body
      wide muscle transduction after a single intravascular injection. Proof-of
      principle has been demonstrated in mouse models of Duchenne muscular dystrophy
      and limb girdle muscular dystrophy. Before initiating clinical trials, it is
      important to validate these promising results in large animal models. More than a
      dozen canine muscular dystrophy models have been developed. Here, we outline a
      protocol for performing systemic AAV gene transfer in neonatal dogs. Implementing
      this technique in dystrophic dogs will accelerate translational muscular
      dystrophy research.

PMID- 21194039
TI  - A translatable, closed recirculation system for AAV6 vector-mediated myocardial
      gene delivery in the large animal.
AB  - Current strategies for managing congestive heart failure are limited, validating
      the search for an alternative treatment modality. Gene therapy holds tremendous
      promise as both a practical and translatable technology platform. Its
      effectiveness is evidenced by the improvements in cardiac function observed in
      vector-mediated therapeutic transgene delivery to the murine myocardium. A large
      animal model validating these results is the likely segue into clinical
      application. However, controversy still exists regarding a suitable method of
      vector-mediated cardiac gene delivery that provides for efficient, global gene
      transfer to the large animal myocardium that is also clinically translatable and
      practical. Intramyocardial injection and catheter-based coronary delivery
      techniques are attractive alternatives with respect to their clinical
      applicability; yet, they are fraught with numerous challenges, including concerns
      regarding collateral gene expression in other organs, low efficiency of vector
      delivery to the myocardium, inhomogeneous expression, and untoward immune
      response secondary to gene delivery. Cardiopulmonary bypass (CPB) delivery with
      dual systemic and isolated cardiac circuitry precludes these drawbacks and has
      the added advantage of allowing for control of the pharmacological milieu,
      multiple pass recirculation through the coronary circulation, the selective
      addition of endothelial permeabilizing agents, and an increase in vector
      residence time. Collectively, these mechanics significantly improve the
      efficiency of global, vector-mediated cardiac gene delivery to the large animal
      myocardium, highlighting a potential therapeutic strategy to be extended to some
      heart failure patients.

PMID- 21194040
TI  - Method of gene delivery in large animal models of cardiovascular diseases.
AB  - Cardiovascular disease is a major cause of morbidity and mortality in
      contemporary societies. While progress in conventional treatment modalities is
      making steady and incremental gains to reduce this disease burden, there remains
      a need to explore new and potentially therapeutic approaches. Gene therapy, which
      was initially envisioned as a treatment strategy for inherited monogenic
      disorders, has been found to hold broader potential that also includes acquired
      polygenic diseases, such as atherosclerosis, arrhythmias, and heart failure.
      Advances in the understanding of the molecular basis of conditions such as these,
      together with the evolution of increasingly efficient gene transfer technology,
      have placed some cardiovascular pathophysiologies within the reach of gene-based
      therapy. In fact, gene therapy holds great promise as a targeted treatment for
      cardiovascular diseases. One of the major hurdles for effective cardiovascular
      gene therapy is the delivery of the viral vectors to the heart. In this chapter,
      we will present the various types of delivery techniques in preclinical, large
      animal models of cardiovascular diseases.

PMID- 21194041
TI  - Percutaneous transendocardial delivery of self-complementary adeno-associated
      virus 6 in the canine.
AB  - Achieving efficient cardiac gene transfer in a large animal model has proven to
      be technically challenging. Prior strategies have employed cardio-pulmonary
      bypass or dual catheterization with the aid of vasodilators to deliver vectors,
      such as adenovirus, adeno-associated virus (AAV) or plasmid DNA. While single
      stranded AAV vectors have shown the greatest promise, they suffer from delayed
      expression, which might be circumvented by using self-complementary vectors. We
      have recently optimized a cardiac gene transfer protocol in the canine using a
      percutaneous transendocardial injection catheter to deliver an AAV vector under
      fluoroscopic guidance. Percutaneous transendocardial injection of self
      complementary AAV (scAAV)-6 is a safe, effective method for achieving efficient
      cardiac gene transfer to approximately 60% of the myocardium.

PMID- 21194042
TI  - Something old, something new--computed tomography studies of the cardiovascular
      system in ancient Egyptian mummies.

PMID- 21194043
TI  - The impact of provider-specific report cards on coronary artery bypass graft
      volume.
AB  - PURPOSE: Reporting states (RS) publish hospital-specific report cards for
      coronary artery bypass graft (CABG) (MS-DRG 235 and 236) surgery. When RS are
      compared with non-reporting states (NRS), do report cards influence the volume of
      CABG surgery performed? METHODS: Using publicly available Medicare data
      (hospitalcompare.hhs.gov) for CABG-only procedures, the volume of CABG procedures
      performed in RS (CA, MA, NJ, NYS, and PA) was compared with the volume of these
      procedures performed in NRS. RESULTS: In the continental US during the financial
      year 2008 a total of 41,589 Medicare patients underwent a CABG (33,318 CABGs in
      NRS versus 8,272 CABGs in RS). A similar percentage of states in each group
      regulated their markets with certificate-of need statutes (30% NRS versus 40%
      RS). Per million capita (pmc), the number of CABG providers in the two groups was
      similar with respect to hospitals (4.1+/-1.6 hospitals pmc in NRS versus 2.9+/
      1.2 hospitals pmc in RS); cardiac surgeons (2.4+/-1.5 surgeons pmc in NRS versus
      5.1+/-2.9 surgeons pmc in RS); and interventional cardiologists (ICs) (18.3+/-5.5
      ICs pmc in NRS versus 21.2+/-5.0 ICs pmc in RS). However, pmc, NRS performed
      significantly more CABG procedures (152.0+/-62.6 CABGs pmc in NRS versus 113.8+/
      31.6 CABG pmc in RS; p=0.05). CONCLUSIONS: States that publish hospital-specific
      report cards perform significantly fewer CABGs per capita than states without
      report cards. As the government's national hospital-specific report card becomes
      more popular, the per capita performance of CABGs in NRS could fall to the level
      found in RS due to the reputational incentives created by the use of hospital
      specific report cards.

PMID- 21194044
TI  - Transradial cardiac catheterization and intervention--observations on its place
      in the catheterization laboratory.

PMID- 21194045
TI  - Using modern communications to manage chronic heart disease.

PMID- 21194046
TI  - Percutaneous mitral valvuloplasty--a new method for balloon sizing based on
      maximal commissural diameter to improve procedural results.
AB  - BACKGROUND: Since the introduction of the Inoue technique for percutaneous
      balloon mitral valvuloplasty (PBMV), various criteria have been proposed for
      ideal balloon sizing. In routine practice, balloon size is chosen based on the
      patient's height according to a simple formula. We tried to define a simple and
      practical echocardiographic measure for adjusting balloon catheter size to
      achieve better success rates and fewer complications. METHODS: Patients with
      moderate to severe mitral stenosis who were candidates for PBMV were selected.
      Maximal mitral commissural diameter at a fully opened state during diastole was
      measured by transthoracic echocardiography and compared with the values from the
      height-based formula. Data were compared by paired sample t-test. RESULTS: Eighty
      three patients (mean age 45+/-13.2 years; 77 female) participated. The median
      balloon size was 28 mm (standard deviation [SD] 1.2) according to the height
      based formula and 26 mm (SD 1.6) according to echocardiography (p<0.001). Using a
      Bland-Altman plot, an excellent agreement was observed between the two methods.
      Regression models were fitted to estimate the balloon size using the patients'
      height, commissural diameter, and mitral valve score. CONCLUSION: Selection of
      balloon size according to echocardiographic commissural diameter is a good
      alternative method. Assuming the possible discrepancy between height-based and
      commissural-based estimated balloon sizes in some cases, adjustment of balloon
      sizes according to the maximal commissural diameter may result in acceptable
      results and fewer complications.

PMID- 21194047
TI  - Patient demographics, complications, and hospital utilization in 250 consecutive
      device implants in a new community hospital electrophysiology program-
      implications for 'niche' hospitals.
AB  - BACKGROUND: Single-center reports on patient demographics and early (<6 weeks)
      device complication rates in academic hospitals are scant and non-existent for
      non-academic community hospital electrophysiology (EP) programs. OBJECTIVE: The
      objective of our study was to examine the demographics, complications, re
      admissions, and accessibility of care in a community EP program to add to the
      body of knowledge of 'real-world' defibrillator implant complications. METHODS:
      Two hundred and fifty consecutive patients who underwent device implantation by a
      single electrophysiologist in a new non-academic community hospital EP program
      starting from its inception in July 2008 were included for analysis. Standard
      procedures for implantation were used. Pacemakers, defibrillators, and generator
      changes were included; temporary pacemakers were excluded. Major complications
      were defined as in-hospital death, cardiac arrest, cardiac perforation, cardiac
      valve injury, coronary venous dissection, hemothorax, pneumothorax, transient
      ischemic attack, stroke, myocardial infarction, pericardial tamponade, and
      arteriovenous fistula. Minor complications were defined as drug reaction,
      conduction block, hematoma or lead dislodgement requiring re-operation,
      peripheral embolus, phlebitis, peripheral nerve injury, and device-related
      infection. RESULTS: This community cohort had similar ejection fractions but was
      older with worse kidney function than those studied in prior reports. There was
      one major early complication (0.4%) and seven minor early complications (2.8%).
      Left ventricular lead placement was successful in 64 of 66 patients (97%).
      CONCLUSIONS: This is the first community-hospital-based EP program to examine
      device implant demographics and outcomes, and revealed an elderly, ill population
      with lower overall rates of complications than seen in national trials and
      available reports from single non-community centers. Contrary to current
      perceptions, these data suggest that community centers may subselect an elderly,
      ill patient population and can provide high-quality, cost-effective, and more
      accessible care.

PMID- 21194048
TI  - Unintended consequences of healthcare reform--patients beware.

PMID- 21194049
TI  - Where have all the patients gone? The decrease in the volume of work of
      cardiologists.

PMID- 21194050
TI  - Computed tomography angiography for right ventricular function in an adult with
      complex congenital heart disease.

PMID- 21194051
TI  - Left bundle branch block--significance of the spatial QRS axis (vector).

PMID- 21194052
TI  - Reversible electrocardiogram changes and cardiomyopathy secondary to baclofen
      withdrawal syndrome.
AB  - Baclofen withdrawal syndrome is a rare and potentially life-threatening condition
      manifesting with autonomic dysreflexia, high fevers, spasticity, seizures, and
      multiorgan failure. Reversible cardiomyopathy due to this condition is extremely
      rare. A high level of suspicion is needed to recognize this condition and start
      an early intervention to improve patient outcome. Electrocardiographic ST-segment
      elevation in lead aVR was previously described in association with left main,
      left anterior descending, and triple-vessel coronary artery disease as well as
      Takotsubo cardiomyopathy. In this article we present a rare case of reversible
      cardiomyopathy due to baclofen withdrawal syndrome associated with diffuse ST
      segment depressions and ST-segment elevation in lead aVR.

PMID- 21194053
TI  - Cardiac tamponade as a rare form of presentation of rheumatic carditis.
AB  - In this article the authors describe a clinical case of acute rheumatic fever
      (according to revised Jones criteria, American Heart Association [AHA], 1992)
      with cardiac tamponade, emphasizing this uncommon presentation. An adolescent
      patient with a clinical picture of cardiac tamponade was seen in the emergency
      department. Clinical progression and tests demonstrated rheumatic carditis with
      an initial manifestation of pericarditis with cardiac tamponade. This report aims
      to warn physicians about the diagnosis of rheumatic carditis in an unusual
      clinical presentation, in cases of cardiac tamponade, particularly in school-aged
      children and adolescents in countries with a high prevalence of rheumatic fever.
      The literature contains only two documented cases of cardiac tamponade related to
      acute rheumatic fever, and this case represents a third.

PMID- 21194054
TI  - Case illustrations of long QT syndrome.
AB  - Long QT syndrome (LQTS) is a rare potentially life-threatening condition.
      Physicians must remain vigilant and consider LQTS as a possible etiology in
      patients with a history of syncope. Prolongation of the QT interval on
      electrocardiogram (ECG) is an essential component for the diagnosis of LQTS,
      despite the limitations of this technique. Experience of analyzing the ECG and
      calculating corrected QTc still remain relevant and are the mainstay diagnostic
      tools. Often, the first sign of the problem is observed after careful evaluation
      of the resting ECG for the hallmark of the disorder. Unfortunately, more than 60%
      of physicians-even cardiologists-have been known to misinterpret the QT interval
      on ECG. The cases discussed in this article highlight the variable clinical
      presentation of prolonged QT interval and the need to be highly vigilant in
      clinical evaluation.

PMID- 21194055
TI  - Cardiac bradyarrhythmias in a patient with cervical spine injury.

PMID- 21194056
TI  - Rotational atherectomy to facilitate stent expansion after deployment in ST
      segment-elevation myocardial infarction.
AB  - We describe successful rotational atherectomy performed in the setting of two
      relative contraindications to the procedure. A 77- year-old female presented with
      ST-segment-elevation myocardial infarction due to 100% right coronary artery
      thrombosis. With high pressure dilatation (22 atmospheres) and cutting balloon
      angioplasty, the lesion dissected but did not fully dilate. After stenting and
      high-pressure post-dilatation at 25 atmospheres the dissection resolved, but a
      70% waist remained. Rotational atherectomy allowed full dilatation of the lesion
      at 22 atmospheres. In this case, after stenting removed angiographically evident
      thrombus and dissection, rotational atherectomy effectively and safely treated
      residual stenosis at an undilatable lesion.

PMID- 21194057
TI  - American healthcare reform agonistes.

PMID- 21194070
TI  - [Message from the President].

PMID- 21194071
TI  - [Editorial: Pharmazie in unserer Zeit 1/2011].

PMID- 21194074
TI  - [BMS-790 052 - an oral antiviral hepatitis C antiviral in the pipeline].

PMID- 21194075
TI  - [SiRNA against hepatitis C?].

PMID- 21194077
TI  - [Systematics and biology of the hepatitis viruses. Like disease - different
      viruses].

PMID- 21194078
TI  - [Diagnosis and clinical features of infection with hepatitis A and hepatitis E
      viruses. Transmission through drinking water and foodstuffs].

PMID- 21194079
TI  - [Clinical features and diagnosis of hepatitis B, C and D. Acute or chronic
      process?].

PMID- 21194081
TI  - [Will a vaccine against hepatitis E soon be available?].

PMID- 21194080
TI  - [Vaccines against viral hepatitis A to E. What do we have, what effect can they
      have?].

PMID- 21194082
TI  - [Current Guidelines for treatment of hepatitis B. Correct diagnosis is the
      prerequisite.].

PMID- 21194083
TI  - [Current Guidelines for treatment of hepatitis C. The eradication of HCV as a
      goal].

PMID- 21194084
TI  - [Future of antiviral therapy for chronic hepatitis C. Direct antiviral acting
      medications].

PMID- 21194085
TI  - [Alfa-interferons. Genetically engineered Antivirals].

PMID- 21194100
TI  - Over- and under-diagnosis of dementia in ethnic minorities: a nationwide register
      based study.
AB  - OBJECTIVE: Among dementia professionals in several European countries, it is
      believed that dementia is under-diagnosed and under-treated to a greater extent
      among ethnic minorities than in the native population. It is unknown whether this
      belief holds true. The objective of this study was to compare the prevalence of
      register-based dementia diagnoses in the largest ethnic minority groups in
      Denmark with the prevalence of register-based dementia diagnoses in the general
      Danish population. METHODS: By linking the Danish hospital registers with the
      Danish Civil Registration System, nationwide dementia cases for three main ethnic
      minorities were identified. Age- and gender-specific prevalence rates for
      dementia were calculated and compared to previously published data for the
      general population. RESULTS: The study population consisted of 68 219 persons
      aged 20 and older. A total of 174 dementia cases were identified. The mean age at
      diagnosis was 57.7 years (SD = 16.2). Compared to the general population, there
      was a higher prevalence of dementia among those younger than 60 years, and a
      markedly lower prevalence of dementia among those 60 years and older.
      CONCLUSIONS: Dementia is under-diagnosed to a greater extent among ethnic
      minorities in the age group 60 years and older but is over-diagnosed in the age
      group younger than 60 years. Several factors may contribute to this pattern,
      including cultural differences in help-seeking behaviour, and problems in
      navigating the health-care system. Furthermore, cross-cultural assessment of
      dementia can be difficult because of language barriers and cultural differences.

PMID- 21194118
TI  - Mechanistic and kinetic characterization of hepatitis C virus NS3 protein
      interactions with NS4A and protease inhibitors.
AB  - The mechanism and kinetics of the interactions between ligands and immobilized
      full-length hepatitis C virus (HCV) genotype 1a NS3 have been characterized by
      SPR biosensor technology. The NS3 interactions for a series of NS3 protease
      inhibitors as well as for the NS4A cofactor, represented by a peptide
      corresponding to the sequence interacting with the enzyme, were found to be
      heterogeneous. It may represent interactions with two stable conformations of the
      protein. The NS3-NS4A interaction consisted of a high-affinity (K(D) = 50 nM) and
      a low-affinity (K(D) = 2 uM) interaction, contributing equally to the overall
      binding. By immobilizing NS3 alone or together with NS4A it was shown that all
      inhibitors had a higher affinity for NS3 in the presence of NS4A. NS4A thus has a
      direct effect on the binding of inhibitors to NS3 and not only on catalysis. As
      predicted, the mechanism-based inhibitor VX 950 exhibited a time-dependent
      interaction with a slow formation of a stable complex. BILN 2061 or ITMN-191
      showed no signs of time-dependent interactions, but ITMN-191 had the highest
      affinity of the tested compounds, with both the slowest dissociation (k(off)) and
      fastest association rate, closely followed by BILN 2061. The k(off) for the
      inhibitors correlated strongly with their NS3 protease inhibitory effect as well
      as with their effect on replication of viral proteins in replicon cell cultures,
      confirming the relevance of the kinetic data. This approach for obtaining kinetic
      and mechanistic data for NS3 protease inhibitor and cofactor interactions is
      expected to be of importance for understanding the characteristics of HCV NS3
      functionality as well as for anti-HCV lead discovery and optimization.

PMID- 21194120
TI  - Molecular mechanism of delta-dendrotoxin-potassium channel recognition explored
      by docking and molecular dynamic simulations.
AB  - delta-Dendrotoxin, isolated from mamba snake venom, has 57 residues cross-linked
      by three disulfide bridges. The protein shares a pharmacological activity with
      other animal toxins, the potent blockade of potassium channels, but is
      structurally unrelated to toxins of different species. We employed alanine
      scanning mutagenesis to explore the molecular mechanism of delta-dendrotoxin
      binding to potassium channels, using protein-protein docking and molecular
      dynamic simulations. In our reasonable model of the delta-dendrotoxin-ShaKv1.1
      complex, delta-dendrotoxin interacted mainly with the N-terminal region and the
      turn of two antiparallel beta-sheets of the channel. This binding mode could well
      explain the functional roles of critical residues in delta-dendrotoxin and the
      ShaKv1.1 channel. Structural analysis indicated that the critical Lys6 residue of
      delta-dendrotoxin plugged its side chain into a channel selectivity filter.
      Another two critical delta-dendrotoxin residues, Lys3 and Arg10, were found to
      contact channel residues through strong polar and nonpolar interactions,
      especially salt-bridge interactions. As for the ShaKv1.1 channel, the channel
      turrets were found in the "half-open state," and two of four Glu423 in the
      turrets of the channel B and D chains could interact, respectively, with Lys3 and
      Lys26 of delta-dendrotoxin through electrostatic interactions. The essential
      Asp431 channel residue was found to associate electrostatically with Arg10 of
      delta-dendrotoxin, and a critical Tyr449 channel residue was just under the
      channel-interacting surface of delta-dendrotoxin. Together, these novel data may
      accelerate the structure-function research of toxins in the dendrotoxin family
      and be of significant value in revealing the diverse interactions between animal
      toxins and potassium channels.

PMID- 21194119
TI  - Avoiding false negative results in specificity analysis of protein-protein
      interactions.
AB  - The competition measurement using simultaneous incubation of labeled and
      unlabeled Ligand is a common method to assess the specificity of a biomolecular
      interaction. In this paper we show that invalid assumptions about the
      interactions may lead to improper experimental setups which in turn can result in
      inaccurate conclusions about the specificity. To improve understanding of
      competition measurements, simulations in MATLAB as well as real-time interaction
      analysis using LigandTracer have been performed. We show that use of a
      concentration of unlabeled Ligand of at least 10 * K(D) is necessary for assay
      accuracy. Increasing the incubation time to assure equilibrium, adding a pre
      incubation phase, and a general understanding of the reversibility of an
      interaction may also improve the reliability of the measurement and the
      conclusions drawn about specificity. These findings may lower the risk of false
      negative results as well as reducing the amount of reagent needed.

PMID- 21194121
TI  - The role of electrostatic interactions in the membrane binding of melittin.
AB  - The binding of melittin and the C-terminally truncated analogue of melittin (21Q)
      to a range of phospholipid bilayers was studied using surface plasmon resonance
      (SPR). The phospholipid model membranes included zwitterionic
      dimyristylphosphatidylcholine (DMPC) and dimyristylphosphatidylethanolamine
      (DMPE), together with mixtures DMPC/dimyristylphosphatidylglycerol (DMPG),
      DMPC/DMPG/cholesterol and DMPE/DMPG. Melittin bound rapidly to all membrane
      mixtures, whereas 21Q, which has a reduced charge, bound much more slowly on the
      DMPC and DMPC/DMPG mixtures reflecting the role of the initial electrostatic
      interaction. The loss of the cationic residues also significantly decreased the
      binding of 21Q with DMPC/DMPG/Cholesterol, DMPE and DMPE/DMPG. The role of
      electrostatics was also highlighted with NaCl in the buffer, which affected the
      way melittin bound to the different membranes, causing a more uniform,
      concentration dependant increase in response. The biosensor results were
      correlated with the conformation of the peptides determined by circular dichroism
      analysis, which indicated that high alpha-helicity was associated with high
      binding affinity. Overall, the results demonstrate that the positively charged
      residues at the C-terminus of melittin play an essential role in membrane
      binding, that modulation of peptide charge influences selectivity of binding to
      different phospholipids and that manipulation of the cationic regions of
      antimicrobial peptides can be used to modulate membrane selectivity.

PMID- 21194122
TI  - Structural prediction and binding analysis of hybridized aptamers.
AB  - Few studies were performed to investigate the molecular recognition capabilities
      of hybridized aptamers. This study is aimed at applying both theoretical
      algorithms and experimental assays to examine the effects of hybridization length
      and region on the secondary structures and binding functionality of hybridized
      aptamers. The experimental results were significantly different from the
      structural predictions in many hybridization conditions. To explain this
      difference, we further proposed a novel equilibrium reaction model that can
      explicitly analyze the molecular interactions between hybridized aptamers and
      their targets. We believe that the research findings and the novel model can be
      used to guide numerous hybridized aptamer-based applications.

PMID- 21194123
TI  - Cystine-knot peptides engineered with specificities for alpha(IIb)beta(3) or
      alpha(IIb)beta(3) and alpha(v)beta(3) integrins are potent inhibitors of platelet
      aggregation.
AB  - A truncated form of the Agouti-related protein (AgRP), a member of the cystine
      knot family, has shown promise as a scaffold for engineering novel peptides with
      new molecular recognition properties. In this study, we replaced a constrained
      six amino acid loop in AgRP with a nine amino acid loop containing an Arg-Gly-Asp
      integrin recognition motif, and randomized the neighboring residues to create a
      library of approximately 20 million AgRP variants. We displayed the AgRP mutants
      as fusions on the surface of yeast and used high-throughput fluorescence
      activated cell sorting (FACS) to isolate peptides that bound specifically to the
      platelet integrin alpha(IIb)beta(3), a clinically important target for the
      prevention and treatment of thrombosis. These AgRP peptides had equilibrium
      dissociation (K(D)) constants for alpha(IIb)beta(3) integrin ranging from 60 to
      90 nM, and did not bind to alpha(v)beta(3), alpha(v)beta(5), or alpha(5)beta(1)
      integrins. Using an alternate library screening strategy, we identified AgRP
      peptides that bound to both alpha(IIb)beta(3) and alpha(v)beta(3) integrins with
      K(D) values ranging from 40 to 70 nM and 20 to 30 nM, respectively, and did not
      bind to alpha(v)beta(5) or alpha(5)beta(1) integrins. Unique consensus sequences
      were identified within both series of AgRP peptides suggesting alternative
      molecular recognition events that dictate different integrin binding
      specificities. In addition, the engineered AgRP peptides prevented platelet
      aggregation as well as or slightly better than the FDA-approved cyclic peptide
      eptifibatide. Collectively, these data demonstrate that cystine-knot peptides can
      be generated with high affinity and specificity to closely-related integrins, and
      provide insights into molecular interactions between small, structured peptide
      ligands and their receptors.

PMID- 21194124
TI  - Reagent validation: an underestimated issue in laboratory practice.

PMID- 21194137
TI  - Impact of PCR for respiratory viruses on antibiotic use: theory and practice.
AB  - RATIONALE FOR THE STUDY: Real-time polymerase chain reaction (PCR) for
      respiratory viruses is more sensitive, yet more expensive, than conventionally
      used direct immunofluorescence (DIF). We determined the impact of real-time PCR,
      additional to DIF, on antibiotic prescription in ventilated children with lower
      respiratory tract infection (LRTI) at admission to the pediatric intensive care
      unit (PICU). METHODS: First, a multicenter survey study was performed.
      Subsequently, in a prospective study, children (<= 5 years) with LRTI were tested
      at admission by DIF and PCR. Positive DIF results were reported at the end of the
      first working day. PICU physicians reported antibiotic treatment on the second
      working day. After informing them of the PCR result antibiotic treatment was
      reevaluated. RESULTS: The multicenter survey study (94 respondents) showed that
      PCR decreased antibiotic use (P < 0.001). In the prospective study 38 children
      were included, of which 19 (50%) were DIF positive. Of the 19 DIF negative
      patients 12 (63%) were treated with antibiotics before revealing the PCR result;
      the PCR test was positive in 9 out of 12. Revealing PCR results did not alter
      antibiotic treatment. In 7 DIF negative patients antibiotics not given, the PCR
      test was positive. CONCLUSION: In contrast to their responses to the survey
      study, in real-life PICU physicians did not let their antibiotic prescription be
      influenced by respiratory real-time PCR in children ventilated for LRTI.

PMID- 21194138
TI  - Lung function and overweight in school aged children after early childhood
      wheezing.
AB  - BACKGROUND AND PURPOSE: Recently, obesity has been connected with wheezing,
      asthma and reduced lung function. Most previous studies have been cross
      sectional. The aim of the present follow-up study was to evaluate the association
      of preceding or current overweight or obesity with lung function at early and
      late school age after early childhood wheezing. MATERIAL AND METHODS: From the
      100 children hospitalized for infection associated wheezing at <24 months of age,
      83 attended the control visit at 4.0 years, 82 at 7.2 years and 81 at 12.3 years
      of age. Flow-volume spirometry was performed in 79 children at 7.2 years and in
      80 children at 12.3 years of age. The weight status was assessed by calculating
      body mass index (BMI) at all visits. Age- and gender-specific BMI standard
      deviation scores (BMI-SDS) of >1.3 SD and >2.0 SD were defined to mean overweight
      and obesity, respectively. RESULTS: Overweight at both 7.2 and 12.3 years of age
      was associated with decreased FEV1 /FVC (forced expiratory volume in 1 sec/forced
      vital capacity). Overweight and obesity at 7.2 years of age were associated with
      decreased FEV1 /FVC and MEF50 (maximal expiratory flow at 50% of FVC) at 12.3
      years of age. The results were similar by continuous and categorized analyses,
      being robust to adjustments for viral findings during early childhood wheezing
      and asthma maintenance medication at school age. CONCLUSION: Overweight and
      obesity are significant risk factors for reduced lung function at school age
      after early childhood wheezing. Thus, early-life wheezers should avoid excessive
      weight gain during childhood.

PMID- 21194139
TI  - Complications of mechanical ventilation in the pediatric population.
AB  - BACKGROUND: Mechanical ventilation (MV) strategies are continuously evolving in
      an effort to minimize adverse events. The objective of this study was to
      determine the complications associated with MV in children. STUDY DESIGN:
      Prospective observational study. Over a period of 10 consecutive months, 150
      patients (median age 0.8 years, IQR 4.4, 59% male) were enrolled in this study.
      RESULTS: The median duration of MV was 3.1 days (IQR 3.9). A total of 85
      complications were observed in 60 (40%) patients (114 complications per 1,000
      ventilation days). 16.7% of patients developed atelectasis, 13.3% post-extubation
      stridor, 9.3% failed extubation, 2.0% pneumothorax, 3.3% accidental extubation,
      2.7% nasal or perioral tissue damage and 1.9% ventilator associated pneumonia.
      Atelectasis occurred most often in the left lower lobe (36%) or in the right
      upper lobe (26%). The incidence of atelectasis in children <1 year of age was 12%
      (31 episodes per 1,000 days of ventilation) compared to 18% (57 episodes per
      1,000 days of ventilation) in children >= 1 year of age (P < 0.05). Patients that
      failed extubation were ventilated for a median of 8.5 (IQR 8.8) days compared to
      2.9 days (IQR, 3.8) in patients that were successfully extubated (P < 0.01). The
      absence of an air leak prior to extubation did not correlate with failed
      extubation. Accidental extubation was limited to orally intubated patients.
      CONCLUSION: MV complications occurred in 40% of patients and most often consisted
      of atelectasis and post-extubation stridor. Further studies are needed to examine
      associated risk factors and strategies to reduce their occurrence.

PMID- 21194140
TI  - Modifiable lifestyle factors impact airway health in non-asthmatic prepubescent
      boys but not girls.
AB  - INTRODUCTION: The prevalence of both childhood obesity and childhood asthma has
      increased dramatically over the past few decades. Little is known concerning the
      role of body composition and lifestyle influences on airway health in children.
      PURPOSE: To determine whether body composition, fruit and vegetable intake (FV)
      and physical activity (PA) impact airway health in healthy prepubescent children.
      METHODS: Pulmonary function tests (forced expiratory flow in 1-sec, forced vital
      capacity, forced expiratory flow at 25-75% of vital capacity) and exhaled nitric
      oxide (eNO) were measured pre- and post-exercise in 40 healthy (20 boys, 20
      girls), non-asthmatic prepubescent children (age 9.7 +/- 0.8 years). PA and FV
      intake were assessed via questionnaire. Each participant completed an incremental
      cycle-ergometer exercise test to exhaustion (V02 max). Body composition was
      measured via Dual Energy X-ray Absorptiometry. Participants were stratified by
      sex for analyses, and follow-up analyses were performed using a clinically
      significant drop in FEV1 of >= 10% to divide participants into groups. RESULTS:
      In the overall group, the change in FEV1 (pre- and post-exercise) was inversely
      related (r = -0.47, P < 0.05) to % body fat; participants with the highest body
      fat demonstrated the greatest decrease in FEV1 (i.e., airway narrowing). When
      participants were divided by sex, this association held true only for boys (r = 
      0.61, P < 0.01). Percent body fat was the only significant contributor to the
      overall prediction of DeltaFEV1 in boys. Boys engaged in significantly more PA
      than girls (3.45 +/- 2.39; 2.00 +/- 1.30 activities/day). Boys also had
      significantly higher V02 max adjusted for lean body mass than girls (48.06 +/-
      5.09; 42.30 +/- 6.06). Body fat percent was not different by sex (P > 0.05). The
      participants in the >= 10% FEV1 group had a significantly greater body fat (28.1
      +/- 9.6%) compared to the <10% drop group (18.8 +/- 9.8%). CONCLUSION: These
      results suggest that PA, FV consumption, and body fat collectively impact airway
      health in prepubescent boys but not girls. Body fat, however, is the only
      independent predictor of post-exercise airway narrowing.

PMID- 21194141
TI  - NerveCenter: COI proposal too costly, academic research groups tell NIH.

PMID- 21194142
TI  - NerveCenter: Embryonic stem cell challenges complicate adult cell research.

PMID- 21194143
TI  - NerveCenter: MIT competition a catalyst for student innovation.

PMID- 21194145
TI  - Neurologic education 2011: new challenges and opportunities.

PMID- 21194146
TI  - Is sudden unexpected death in epilepsy due to postictal brain shutdown?

PMID- 21194147
TI  - Expanding the evidence base for therapeutics in myasthenia gravis.

PMID- 21194148
TI  - Cerebral pseudoatrophy or real atrophy after therapy in multiple sclerosis.

PMID- 21194149
TI  - Are we making progress in the understanding of tremor in Parkinson's disease?

PMID- 21194150
TI  - The authorship lottery: an impediment to research collaboration?
AB  - Authorship of scientific publications holds great importance for basic and
      clinical researchers. Academic appointments and promotions, grant funding, and
      salary support depend to some extent on published recognition through authorship.
      Peer-recognition and personal satisfaction are additional incentives for
      authorship. Some current "rules" and conventions for assigning authorship are
      based on largely unwritten but widely-accepted arbitrary decisions. We
      hypothesize that the inherent uncertainties about assigning "credit where credit
      is due" serve as a disincentive for clinicians considering an academic career and
      may discourage or at least impede the collaborations essential to address most
      translational and clinical research issues. Surveys of the New England Journal of
      Medicine and the Annals of Neurology suggest that neurologists have been slow to
      adopt ways of sharing "credit" appropriately. We recommend that authorship of
      reports of the primary results of multicenter or multidisciplinary studies should
      be in the name of the group of investigators collaborating on the work. Given the
      availability of digital methods that could apportion credit quantitatively,
      academic leaders, including funding agencies and promotions committees, should
      consider challenging outmoded authorship conventions. Authorship is too important
      to be left to chance.

PMID- 21194151
TI  - Evidence for acute neurotoxicity after chemotherapy.
AB  - OBJECTIVE: Chronic neurotoxicity is a recognized long-term complication following
      chemotherapy in a range of diseases. Neurotoxicity adversely affects patients'
      quality of life. The objective of this study is to examine whether there is
      evidence of acute neurotoxicity. METHODS: This prospective study included
      patients with secondary progressive multiple sclerosis (SPMS-BMT, n = 14) and
      hematological malignancies (HM-BMT, n = 17) receiving chemotherapy as
      preconditioning for bone marrow transplant. The control groups included SPMS
      patients matched for demographic and clinical data (SPMS-PL, n = 14) and healthy
      controls (n = 14). Neurodegeneration was assessed at baseline and longitudinally
      (months 1, 2, 3, 6, 9, 12, 24, and 36), combining a clinical scale for disability
      (Expanded Disability Status Scale [EDSS]), a serum protein biomarker for
      neurodegeneration (neurofilaments, NfH-SMI35), and brain atrophy measures
      (magnetic resonance imaging). RESULTS: Disability progression was significantly
      more acute and severe following chemotherapy compared to placebo. Immediately
      after starting chemotherapy, serum NfH-SMI35 levels increased in 79% (p < 0.0001)
      of SPMS-BMT patients and 41% (p < 0.01) of HM-BMT patients compared to 0% of SPMS
      PL patients or healthy controls. In SPMS-BMT serum NfH-SMI35 levels were > 100
      fold higher 1 month after chemotherapy (29.73ng/ml) compared to baseline
      (0.28ng/ml, p < 0.0001). High serum NfH-SMI35 levels persisting for at least 3
      months were associated with sustained disability progression on the EDSS (p <
      0.05). Brain atrophy rates increased acutely in SPMS-BMT (-2.09) compared to SPMS
      PL (-1.18, p < 0.05). INTERPRETATION: Neurotoxicity is an unwanted acute side
      effect of aggressive chemotherapy.

PMID- 21194152
TI  - Involvement of the cerebellothalamocortical pathway in Parkinson disease.
AB  - OBJECTIVE: Lesioning or stimulation of the cerebellar thalamus is an established
      treatment for rest and postural tremors in Parkinson disease (PD). The
      cerebellothalamocortical (CTC) pathway can be assessed by transcranial magnetic
      stimulation (TMS) of the cerebellum, which suppresses the contralateral primary
      motor cortex (M1), a phenomenon termed cerebellar inhibition (CBI). Tremor reset
      can be used to assess whether the stimulated brain area is involved in the
      generation or transmission of tremor. We tested whether M1 or cerebellar
      stimulation can reset PD tremor, and investigated the excitability of the CTC
      pathway in PD. METHODS: Ten mild to moderate PD patients in the OFF medication
      state and 10 healthy controls were studied. Tremor reset was tested with TMS
      delivered to the cerebellum or M1. CBI was assessed by cerebellar stimulation
      followed by M1 stimulation at interstimulus intervals of 3 to 8 milliseconds.
      Subjects were tested both at rest and during arm extension. RESULTS: Rest tremor
      in PD was reset by M1 stimulation but not by cerebellar stimulation. Postural
      tremor was reset by both types of stimulation. At rest, CBI was reduced in PD
      patients compared to controls. Arm extension decreased CBI in controls and turned
      the inhibition into facilitation in patients. CBI correlated with the degree of
      tremor reset caused by the cerebellar stimulation. INTERPRETATION: The
      excitability of CTC pathway is decreased in PD. Rest and postural tremors in PD
      are mediated by different neuronal pathways, and the CTC pathway is involved in
      the generation or transmission of postural tremor.

PMID- 21194153
TI  - Glut1/SLC2A1 is crucial for the development of the blood-brain barrier in vivo.
AB  - OBJECTIVE: The overall permeability of the blood-brain barrier (BBB) is regulated
      by specialized cerebral endothelial cells and their junctional complexes,
      consisting of adherens junctions (AJs) and tight junctions (TJs). Among the
      members of the glucose transporters (Glut), Glut1 is a unique molecule expressed
      in the cerebral endothelial cells. Glut1 and the junctional proteins are
      concomitantly downregulated in situations in which breakdown of the BBB has taken
      place. We hypothesized that the expression of Glut1 may play a significant role
      in the development of the cerebral microvasculature with BBB properties. To date,
      there is no information on the role of Glut1 during the development of BBB. In
      the present study, the in vivo effects of Glut1 knockdown on the cerebral
      vascular development were investigated. METHODS: Zebrafish was used as a model
      organism. We confirmed that the structure of the zebrafish homologue of Glut1 is
      highly similar to the human Glut1 and that the function of the Glut1-mediated
      cerebral uptake of glucose is evolutionally conserved. RESULTS: In the Glut1
      knockdown model, we observed loss of the cerebral endothelial cells, with
      concomitant downregulation of the junctional proteins important for intactness of
      the AJs/TJs and impaired cerebral circulation. The resulting leaky BBB caused
      vasogenic brain edema. INTERPRETATION: The data suggest a crucial role of Glut1
      in the development of the cerebral endothelial cells with BBB properties in vivo.
      The findings suggest that modulation of Glut1 expression and function may open
      new directions of research for therapeutic strategies to prevent vasogenic brain
      edema.

PMID- 21194154
TI  - Reversible infantile respiratory chain deficiency: a clinical and molecular
      study.
AB  - OBJECTIVE: To characterize the clinical features and clarify the pathogenicity of
      "benign cytochrome c oxidase deficiency myopathy." METHODS: The study included 8
      patients with the phenotype of this disease. Six patients underwent muscle
      biopsies and all the 8 underwent mitochondrial DNA analyses. To confirm the
      pathogenicity of the detected mitochondrial DNA mutation, we performed northern
      blot analysis, using muscle specimens, and blue native polyacrylamide gel
      electrophoresis and respiratory chain enzyme activity assay of transmitochondrial
      cell lines (cybrids). RESULTS: Clinical symptoms were limited to skeletal muscle
      and improved spontaneously in all cases; however, 2 siblings had basal ganglia
      lesions. In all patients, we identified a homoplasmic m.14674T>C or m.14674T>G
      mitochondrial transfer RNA-glutamate mutation. Northern blot analysis revealed
      decreased levels of mitochondrial transfer RNA-glutamate molecules. Muscle
      specimens and cybrids derived from patients showed decreased activity of
      respiratory complexes IV, and/or I, III; however, this was normal in naive
      myoblasts. INTERPRETATION: Identification of a novel m.14674T>G mutation in
      addition to m.14674T>C indicated the importance of this site for disease
      causation. Analyses of cybrids revealed the pathogenicity of m.14674T>C mutation,
      which resulted in defects of cytochrome c oxidase and multiple respiratory chain
      enzymes. Furthermore, patients with basal ganglia lesions provided new insights
      into this disease, in which only skeletal muscle was thought to be affected.
      Normal respiratory chain enzyme activities in naive myoblasts suggested the
      compensatory influence of nuclear factors, which may be a clue to understanding
      the mechanisms of spontaneous recovery and low penetrance in families carrying
      the mutation.

PMID- 21194155
TI  - Dysexecutive syndrome: diagnostic criteria and validation study.
AB  - OBJECTIVE: Disorders of executive functions are among the most frequent cognitive
      deficits, but they remain poorly defined and are subject to heterogeneous
      assessment. To address this major issue, the Groupe de Reflexion sur l'Evaluation
      des Fonctions Executives (GREFEX) group has proposed criteria for behavioral and
      cognitive dysexecutive syndromes and has designed a battery including a specific
      heteroquestionnaire and 7 cognitive tests. We investigated the frequency of
      behavioral and cognitive dysexecutive disorders in patients suffering from
      various diseases and the association of these disorders with loss of autonomy.
      METHODS: A total of 461 patients aged between 16 and 90 years with severe
      traumatic brain injury, stroke, mild cognitive impairment, Alzheimer disease,
      multiple sclerosis, and Parkinson disease were recruited into this prospective
      cohort study by 21 centers between September 2003 and June 2006. Behavioral and
      cognitive dysexecutive disorders were examined using the GREFEX battery. RESULTS:
      A dysexecutive syndrome was observed in 60% of patients, concerning both
      behavioral and cognitive domains in 26% and dissociated in 34%. All behavioral
      and cognitive dysexecutive disorders discriminated (p = 0.001, all) patients from
      controls. The pattern of cognitive syndrome differed (p = 0.0001) according to
      the disease. Finally, behavioral (odds ratio [OR], 4.6; 95% confidence interval
      [CI], 2. 3-9.1; p = 0.0001) and cognitive (OR, 3.36; 95% CI, 1.7-6.6; p = 0.001)
      dysexecutive syndromes and Mini Mental State Examination score (OR, 0.79; 95% CI,
      0.68-0.91; p = 0.002) were independent predictors of loss of autonomy.
      INTERPRETATION: This study provided criteria of dysexecutive syndrome and showed
      that both behavioral and cognitive syndromes contribute to loss of autonomy.
      Profiles vary across patients and diseases, and therefore systematic assessment
      of behavioral and cognitive disorders in reference to diagnostic criteria is
      needed.

PMID- 21194158
TI  - Neuroplasticity predicts outcome of optic neuritis independent of tissue damage.

PMID- 21194160
TI  - "Double crush" in Parkinson's disease.

PMID- 21194156
TI  - Hippocampal hyperactivation in presymptomatic familial Alzheimer's disease.
AB  - OBJECTIVE: The examination of individuals who carry fully penetrant genetic
      alterations that result in familial Alzheimer's disease (FAD) provides a unique
      model for studying the early presymptomatic disease stages. In AD, deficits in
      episodic and associative memory have been linked to structural and functional
      changes within the hippocampal system. This study used functional MRI (fMRI) to
      examine hippocampal function in a group of healthy, young, cognitively-intact
      presymptomatic individuals (average age 33.7 years) who carry the E280A
      presenilin-1 (PS1) genetic mutation for FAD. These PS1 subjects will go on to
      develop the first symptoms of the disease around the age of 45 years. Our
      objective was to examine hippocampal function years before the onset of clinical
      symptoms. METHODS: Twenty carriers of the Alzheimer's-associated E280A PS1
      mutation and 19 PS1-negative control subjects participated. Both groups were
      matched for age, sex, education level, and neuropsychological test performance.
      All participants performed a face-name associative encoding task while in a
      Phillips 1.5T fMRI scanner. Analysis focused on the hippocampal system. RESULTS:
      Despite identical behavioral performance, presymptomatic PS1 mutation carriers
      exhibited increased activation of the right anterior hippocampus during encoding
      of novel face-name associations compared to matched controls. INTERPRETATION: Our
      results demonstrate that functional changes within the hippocampal memory system
      occur years before cognitive decline in FAD. These presymptomatic changes in
      hippocampal physiology in FAD suggest that hippocampal fMRI patterns during
      associative encoding may also provide a preclinical biomarker in sporadic AD.

PMID- 21194162
TI  - A case series of peripheral neuropathy in patients with Parkinson's disease.

PMID- 21194164
TI  - Neurotoxic cycad components and Western Pacific ALS/PDC.

PMID- 21194166
TI  - Pulmonary surfactant in respiratory syncytial virus bronchiolitis: the role in
      pathogenesis and clinical implications.
AB  - Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of lower
      respiratory tract infection, and the most frequent reason for hospitalization
      among infants throughout the world. In addition to the acute consequences of the
      disease, RSV bronchiolitis in early childhood is related to further development
      of recurrent wheezing and asthma. Despite the medical and economic burden of the
      disease, therapeutic options are limited to supportive measures, and mechanical
      ventilation in severe cases. Growing evidence suggests an important role of
      changes in pulmonary surfactant content and composition in the pathogenesis of
      severe RSV bronchiolitis. Besides the well-known importance of pulmonary
      surfactant in maintenance of pulmonary homeostasis and lung mechanics, the
      surfactant proteins SP-A and SP-D are essential components of the pulmonary
      innate immune system. Deficiencies of such proteins, which develop in severe RSV
      bronchiolitis, may be related to impairment in viral clearance, and exacerbated
      inflammatory response. A comprehensive understanding of the role of the pulmonary
      surfactant in the pathogenesis of the disease may help the development of new
      treatment strategies. We conducted a review of the literature to analyze the
      evidences of pulmonary surfactant changes in the pathogenesis of severe RSV
      bronchiolitis, its relation to the inflammatory and immune response, and the
      possible role of pulmonary surfactant replacement in the treatment of the
      disease.

PMID- 21194167
TI  - Age of Pseudomonas aeruginosa acquisition and subsequent severity of cystic
      fibrosis lung disease.
AB  - RATIONALE: Pseudomonas aeruginosa (Pa) is associated with poor pulmonary outcomes
      in cystic fibrosis (CF), but the association between age of Pa infection and
      severity of subsequent lung disease has not been thoroughly investigated.
      OBJECTIVE: Our goal was to determine the association between age of Pa
      acquisition and subsequent severity of CF lung disease. METHODS: Case-control
      study using CF Foundation Registry data of 629 DeltaF508 homozygotes with severe
      and mild lung disease (FEV1 in the lowest and highest quartile of birth cohort,
      respectively). Multivariate logistic regression was performed to determine the
      association between age of Pa acquisition and lung disease severity. RESULTS:
      Earlier age of Pa infection was strongly associated with increased odds of severe
      lung disease. For first and persistent Pa, adjusted odds ratios for severe lung
      disease were 6.5 (95% CI 3.1, 13.7; P < 0.0001) and 11.2 (5.4, 23.1; P < 0.0001),
      respectively, for subjects with infection before age 5 versus at >= 10 years; the
      association was stronger in females than males. CONCLUSIONS: Earlier Pa
      infection, particularly before 5 years of age, is strongly associated with severe
      CF lung disease later in life. This study is not designed to determine causality;
      Pa infection may be causing lung injury, or may be a marker of ongoing
      inflammation and lung damage in young children with CF.

PMID- 21194170
TI  - "Cepacia syndrome" associated with Burkholderia cepacia (Genomovar I) infection
      in an adolescent with cystic fibrosis.

PMID- 21194168
TI  - Low birth weight and respiratory hospitalizations in adolescence.
AB  - OBJECTIVE: Some low birth weight survivors are at increased risk of respiratory
      disease. We studied whether low birth weight was associated with hospitalization
      for respiratory illness in adolescence and to what degree bronchopulmonary
      dysplasia, cerebral palsy, and other comorbidities accounted for this
      association. METHODS: We performed a population-based retrospective cohort study
      using Washington State birth certificates from 1987 to 1994 to identify exposed
      (low birth weight) and unexposed (normal birth weight) subjects. Normal birth
      weight subjects were randomly selected from birth certificates, frequency matched
      to low birth weight subjects by birth year. Deaths prior to age 12 were excluded.
      The primary exposure was low birth weight: subcategorized as moderately-low-birth
      weight (1,500-2,499 g) and very-low-birth weight (<1,500 g). The primary outcome
      was the first respiratory related hospitalization between the ages of 12-20.
      Respiratory hospitalizations were defined by ICD-9 discharge diagnosis codes.
      RESULTS: After adjustment, the hazard ratio for hospitalization was 1.39 for
      moderately-low-birth weight (95% CI 1.17-1.65, P < 0.001) and 2.52 for very-low
      birth weight (1.80-3.53, P < 0.001). Controlling for bronchopulmonary dysplasia
      attenuated the risk for very-low-birth weight to 1.76 (1.17-2.64; P = 0.006). A
      similar attenuation was seen after controlling for cerebral palsy [HR 1.49 (1.02
      2.18), P = 0.04], suggesting that some of the risk is mediated through these
      diagnoses. Among moderately-low-birth weight survivors, controlling for these
      diagnoses had less of an effect. CONCLUSIONS: Low birth weight was associated
      with an increased risk of respiratory hospitalizations in adolescence.
      Comorbidities explained some of this risk. However, low birth weight remained
      independently associated with an increased risk of hospitalization.

PMID- 21194171
TI  - Efficacy of metered-dose inhalers for children with acute asthma exacerbations.
AB  - OBJECTIVE: To compare the effectiveness of the administration of inhaled beta
      agonists delivered via a metered-dose inhaler (MDI) with spacers--as part of an
      evidence-based asthma pathway developed to manage acute asthma exacerbations in
      children at the emergency room level and in inpatient management--against
      administration via nebulization. DESIGN: Case with historical control. SETTING:
      KK Women's and Children's Hospital (Singapore). PARTICIPANTS: A total of 19,951
      children (infants to older children) aged 18 years and younger who attended the
      emergency room for asthma exacerbations. MAIN OUTCOME MEASURES: Average length of
      stay, proportion admitted to high dependency or intensive care, proportion
      readmitted for unresolved symptoms within 72 hr, cost per patient and overall.
      RESULTS: There was no increase in the mean proportion of emergency room
      attendances admitted to inpatient care with use of an MDI (mean difference 0.97%,
      95% CI: -1.6-3.5%, P = 0.447), nor of children admitted to intensive care (0.21
      vs. 0.20 pre- and post-pathway, P = 0.827) or to high dependency units (2.21 vs.
      1.37 pre- and post-pathway, P = 0.200) but a significant reduction in the within
      72 hr re-attendance rate (mean difference 1.4%, 95% CI: 0.78-2.0%, P < 0.001)
      with use of an MDI. The average length and cost per patient for an inpatient stay
      for acute asthma exacerbations was reduced with use of an MDI. CONCLUSIONS: The
      use of an MDI with spacer as part of an evidence-based asthma pathway was
      effective in the management of acute asthma exacerbations in the emergency room
      setting and for inpatient management.

PMID- 21194172
TI  - Race and asthma control in the pediatric population of Hawaii.
AB  - OBJECTIVES: The racially unique population of Hawaii has one of the highest
      prevalences of childhood asthma in America. We estimate the prevalence of
      impaired asthma control among asthmatic children in Hawaii and determine which
      factors are associated with impaired control. PATIENTS AND METHODS: We analyzed
      data from 477 asthmatic children living in Hawaii participating in the 2006-2008
      Behavioral Risk Factor Surveillance System (BRFSS) Asthma Call-Back Surveys.
      Impaired asthma control was modeled after 2007 National Asthma Education and
      Prevention Program guidelines. Univariate and multivariate analyses were used to
      identify factors associated with impaired asthma control. RESULTS: Children
      (53.8%) with asthma were either part or full Native Hawaiian/Pacific Islander.
      While 35.6% of asthmatic children met criteria for impaired asthma control, being
      part or full Native Hawaiian/Pacific Islander was not associated with impaired
      control. Only 31.1% of children with impaired control reported the use of inhaled
      corticosteroids despite >80% having had a routine checkup for asthma in the past
      year and receipt of asthma education from a healthcare provider. CONCLUSION: A
      large proportion of asthmatic children in Hawaii have impaired asthma control
      that does not appear to be associated with race but may be associated with
      inadequate pharmacologic therapy. While a significant percentage reported
      receiving routine asthma care and asthma education, a minority reported using
      inhaled corticosteroids. Reasons for this discrepancy between asthma assessment
      and treatment are unclear. However, additional education on part of the
      physician, community, and healthcare system are likely to improve management and
      reduce morbidity in this population.

PMID- 21194173
TI  - Relation between partial and raised volume forced expiratory flows in sick
      infants.
AB  - RATIONALE: The maximal expiratory flow-volume (MEFV) and the partial expiratory
      flow-volume (PEFV) maneuvers are interchangeably performed when testing infant
      lung function. In recent years, the MEFV has gained popularity over the PEFV as
      it offers the investigator various forced expiratory flow and volume variables in
      addition to the sole, maximal flow at functional residual capacity (Vmax FRC)
      available from the PEFV maneuver. Both types of measure are considered to provide
      information on airway function. OBJECTIVES: To compare Vmax FRC values by PEFV to
      flows at low lung volumes by MEFV in infants suffering from a variety of
      illnesses. METHODS: Retrospective analysis of records of 175 infants attending a
      tertiary out-patient clinic (age range 2-234 weeks). Comparisons between
      parameters derived from the PEFV and MEFV curves were made by linear regression
      and by Bland-Altman plots. MEASUREMENTS AND MAIN RESULTS: Vmax FRC highly
      correlated with forced expiratory flows at 85% of forced vital capacity (FEF85; r
      = 0.87, P < 0.0001) with a mean bias of 20 ml/sec, and at 75% (FEF75; r = 0.83, P
      < 0.0001) with a greater mean bias of -72 ml/sec, but less with forced expired
      volume in 0.5 sec (FEV0.5; r = 0.66, P < 0.0001) showing a much wider scatter
      especially in infants with more severe obstruction. Same agreement between Vmax
      FRC and FEF85 or FEF75 was seen when presented as z-scores (r = 0.77 and 0.76;
      respectively). CONCLUSIONS: Regardless of the maneuver performed, PEFV or MEFV,
      Vmax FRC and FEF85, and FEF75 show high agreement in sick infants. As they both
      describe small airways function, both maneuvers may be interchangeable.

PMID- 21194174
TI  - Life-threatening anaphylactic reaction after the administration of airway topical
      lidocaine.
AB  - A 9-year-old boy who developed a life-threatening anaphylaxis reaction of the
      airway and subsequent dyspnea and circulation collapse because of instilled the
      topical lidocaine into the airway within 2 min before performing flexible
      bronchoscopy (FB). FB revealed swollen airway mucosa and extensive foamy
      secretion that severely compromised the ventilation lumen. Rapid detection with
      FB and immediate resuscitation, including prompt administration of epinephrine,
      volume expander, and positive pressure ventilation with pure oxygen via an
      endotracheal tube, were successfully save the patient's life.

PMID- 21194175
TI  - Pulmonary sequestration of the left upper lobe associated with a bronchogenic
      cyst: case report of an exceptional association.
AB  - Intralobar pulmonary sequestration (ILPS) and bronchogenic cyst are rare
      congenital diseases. We present the first case of the association between an ILPS
      located in the upper lobe and a bronchogenic cyst. This association has been
      discovered antenatally in a girl. The cystic lesion has been shown by a fetal MRI
      and confirmed by a CT scan at 3 weeks of life. She underwent a left upper
      lobectomy by thoracoscopy at the age of 5 months. Postoperative course was
      uneventfull. This case confirms the congenital origin of pulmonary sequestration
      and shows the interest of an early surgery.

PMID- 21194176
TI  - A comparison of the bioaccumulation potential of three freshwater organisms
      exposed to sediment-associated contaminants under laboratory conditions.
AB  - In the field of sediment quality assessment, increased support has been expressed
      for using multiple species that represent different taxa, trophic levels, and
      potential routes of exposure. However, few studies have compared the
      bioaccumulation potential of various test species over a range of sediment
      contaminants (hydrophobic organics and metals). As part of the development and
      standardization of a laboratory bioaccumulation method for the Ontario Ministry
      of the Environment, the oligochaete Lumbriculus variegatus, mayfly nymph
      Hexagenia spp., and juvenile fathead minnow Pimephales promelas were exposed to a
      variety of field-contaminated sediments (n = 10) to evaluate their relative
      effectiveness for accumulating different contaminants (e.g.,
      dichlorodiphenyltrichloroethane [DDT] and metabolites, polychlorinated biphenyls
      [PCBs), polycyclic aromatic hydrocarbons [PAHs), polychlorinated dibenzo-p
      dioxins and dibenzofurans [PCDD/Fs), and heavy metals). Bioaccumulation was
      usually highest in L. variegatus but also most variable within and (relative
      measures) between sediments. Bioaccumulation was similar between L. variegatus
      and Hexagenia spp. in most of the sediments tested. Significant differences in
      bioaccumulation between species were observed for DDT,
      dichlorodiphenyldichloroethane (DDD), PAHs, and PCDD/Fs. The present study
      indicates that species-specific differences in bioaccumulation may, but do not
      always, exist and can vary with contaminant and sediment type. The choice of test
      species or combination to use in a standard test method may depend on the
      objectives of the sediment quality assessment and data requirements of an
      ecological risk assessment. The results of the present study provide insight for
      selection of test species and validation of laboratory methods for assessing
      bioaccumulation with these species, as well as valuable information for
      interpreting results of bioaccumulation tests.

PMID- 21194177
TI  - Assessment of supercritical fluid extraction use in whole sediment toxicity
      identification evaluations.
AB  - Supercritical fluid extraction (SFE) with pure CO(2) was assessed as a
      confirmatory tool in phase III of whole sediment toxicity identification
      evaluations (TIEs). The SFE procedure was assessed on two reference sediments and
      three contaminated sediments by using a combination of toxicological and chemical
      measurements to quantify effectiveness. Sediment toxicity pre- and post-SFE
      treatment was quantified with a marine amphipod (Ampelisca abdita) and mysid
      (Americamysis bahia), and nonionic organic contaminants (NOCs) polychlorinated
      biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) were measured in
      sediments, overlying waters, and interstitial waters. In general, use of SFE with
      the reference sediments was successful, with survival averaging 91% in post-SFE
      treatments. Substantial toxicity reductions and contaminant removal from
      sediments and water samples generated from extracted sediments of up to 99% in
      two of the contaminated sediments demonstrated SFE effectiveness. Furthermore,
      toxicological responses for these SFE-treated sediments showed comparable results
      to those from the same sediments treated with the powdered coconut charcoal
      addition manipulation. These data demonstrated the utility of SFE in phase III of
      a whole sediment TIE. Conversely, in one of the contaminated sediments, the SFE
      treatments had no effect on sediment toxicity, whereas sediment concentrations of
      PCBs and PAHs were reduced. We propose that, for some sediments, the SFE
      treatment may result in the release of otherwise nonbioavailable cationic metals
      that subsequently cause toxicity to test organisms. Overall, SFE treatment was
      found to be effective for reducing the toxicity and concentrations of NOCs in
      some contaminated sediments. However, these studies suggest that SFE treatment
      may enhance toxicity with some sediments, indicating that care must be taken when
      applying SFE and interpreting the results.

PMID- 21194178
TI  - Effect of 2,4-dihydroxybenzophenone (BP1) on early life-stage development of the
      marine copepod Acartia tonsa at different temperatures and salinities.
AB  - Benzophenone (BP)-type ultraviolet (UV) filters are widely used in cosmetic and
      sunscreen products and can enter the aquatic environment. Therefore, we
      investigated the subchronic toxicity of 2,4-dihydroxybenzophenone (BP1) on the
      marine calanoid copepod Acartia tonsa in an early life-stage development study.
      Since developmental endpoints depend on environmental conditions, a preceding
      study of A. tonsa development was performed at three temperatures, four
      salinities, four light:dark regimes, six food densities, and four culture
      densities. Times elapsed until 50% of the population had reached a copepodite
      stage (DT(1/2) ) at the different conditions were calculated. The DT(1/2) values
      decreased from 296 h at 15 degrees C to 89 h at 25 degrees C and were also
      affected by salinity (126 h at 150/00 and 167 h at 300/00), whereas the
      light:dark regime and culture density influenced development only to a minor
      extent. BP1 was found acutely toxic at 2.6 mg/L (48-h median lethal concentration
      [LC50]). The toxicity of BP1 on early life-stage development was studied in
      combinations of three temperatures (15, 20, 25 degrees C) and three salinities
      (15, 20, 250/00) using five toxicant concentrations between 0.051 and 2 mg/L in
      each scenario. Concentrations causing 10 and 50% inhibition of development (EC10
      and EC50) were determined. Acartia tonsa was most resistant towards BP1 at 20
      degrees C where an EC50 of 1.1 mg/L was found, whereas EC50 values were
      significantly lower at 15 degrees C (0.49 mg/L) and 25 degrees C (0.77 mg/L),
      respectively. The EC50 also decreased with increasing salinity. Our results
      demonstrate that environmental conditions do influence toxicity test results;
      thus, they need to be considered carefully when developing test protocols as well
      as for environmental risk assessments of chemicals.

PMID- 21194179
TI  - Oxidative stress response of Forster's terns (Sterna forsteri) and Caspian terns
      (Hydroprogne caspia) to mercury and selenium bioaccumulation in liver, kidney,
      and brain.
AB  - Bioindicators of oxidative stress were examined in prebreeding and breeding adult
      and chick Forster's terns (Sterna forsteri) and in prebreeding adult Caspian
      terns (Hydroprogne caspia) in San Francisco Bay, California. Highest total
      mercury (THg) concentrations (mean +/- standard error; ug/g dry wt) in liver
      (17.7 +/- 1.7), kidney (20.5 +/- 1.9), and brain (3.0 +/- 0.3) occurred in
      breeding adult Forster's terns. The THg concentrations in liver were
      significantly correlated with hepatic depletion of reduced glutathione (GSH),
      increased oxidized glutathione (GSSG):GSH ratio, and decreased hepatic gamma
      glutamyl transferase (GGT) activity in adults of both tern species. Prefledging
      Forster's tern chicks with one-fourth the hepatic THg concentration of breeding
      adults exhibited effects similar to adults. Total mercury-related renal GSSG
      increased in adults and chicks. In brains of prebreeding adults, THg was
      correlated with a small increase in glucose-6-phosphate dehydrogenase (G-6-PDH)
      activity, suggestive of a compensatory response. Brain THg concentrations were
      highest in breeding adult Forster's terns and brain tissue exhibited increased
      lipid peroxidation as thiobarbituric acid-reactive substances, loss of protein
      bound thiols (PBSH), and decreased activity of antioxidant enzymes, GSSG
      reductase (GSSGrd), and G-6-PDH. In brains of Forster's tern chicks there was a
      decrease in total reduced thiols and PBSH. Multiple indicator responses also
      pointed to greater oxidative stress in breeding Forster's terns relative to
      prebreeding terns, attributable to the physiological stress of reproduction. Some
      biondicators also were related to age and species, including thiol
      concentrations. Enzymes GGT, G-6-PDH, and GSSGred activities were related to
      species. Our results indicate that THg concentrations induced oxidative stress in
      terns, and suggest that histopathological, immunological, and behavioral effects
      may occur in terns as reported in other species.

PMID- 21194181
TI  - Risk of venous thromboembolic disease in postmenopausal women taking oral or
      transdermal hormone replacement therapy.
AB  - OBJECTIVE: The influence of hormone replacement therapy (HRT) on hemostasis
      processes depends on the type of hormone, the combination of doses, the time of
      taking HRT, and the route of administration (oral, transdermal, implanted). The
      aim of the current study was to assess some parameters of coagulation, especially
      tissue factor pathway inhibitor (TFPI) and tissue factor (TF) in postmenopausal
      women using oral or transdermal HRT. METHODS: The study was conducted on 76
      healthy women, including 46 women aged 44-58 years who were taking oral (26) or
      transdermal (20) HRT, and 30 women aged 44-54 years who did not take HRT as the
      control group. Plasma concentrations of TF, TFPI, thrombin-antithrombin complex
      (TAT), and D-dimer were performed by enzyme-linked immunosorbent assay (ELISA).
      Moreover, the concentration of fibrinogen and activity of protein C were measured
      by chromogenic and chronometric methods. RESULTS: We observed a significantly
      higher concentration of TF and a significantly lower concentration of TFPI in
      women taking oral and transdermal HRT in comparison with the control group. We
      also found a significantly lower concentration of fibrinogen in women taking oral
      HRT vs. the control group. Moreover, no statistically significant changes in
      concentrations of TAT and D-dimer, or activity of protein C were noted.
      CONCLUSIONS: In this study, the occurrence of an increased TF concentration
      simultaneously with a decreased concentration of TFPI in women taking HRT
      indicates hypercoagulability. No significant modification of TAT or D-dimer
      occurred, and thus there may not be increased risk of thrombosis.

PMID- 21194180
TI  - Whole genome amplification in preimplantation genetic diagnosis.
AB  - Preimplantation genetic diagnosis (PGD) refers to a procedure for genetically
      analyzing embryos prior to implantation, improving the chance of conception for
      patients at high risk of transmitting specific inherited disorders. This method
      has been widely used for a large number of genetic disorders since the first
      successful application in the early 1990s. Polymerase chain reaction (PCR) and
      fluorescent in situ hybridization (FISH) are the two main methods in PGD, but
      there are some inevitable shortcomings limiting the scope of genetic diagnosis.
      Fortunately, different whole genome amplification (WGA) techniques have been
      developed to overcome these problems. Sufficient DNA can be amplified and
      multiple tasks which need abundant DNA can be performed. Moreover, WGA products
      can be analyzed as a template for multi-loci and multi-gene during the subsequent
      DNA analysis. In this review, we will focus on the currently available WGA
      techniques and their applications, as well as the new technical trends from WGA
      products.

PMID- 21194182
TI  - Immunomodulative effects of mesenchymal stem cells derived from human embryonic
      stem cells in vivo and in vitro.
AB  - OBJECTIVE: Human embryonic stem cells (hESCs) have recently been reported as an
      unlimited source of mesenchymal stem cells (MSCs). The present study not only
      provides an identical and clinically compliant MSC source derived from hESCs
      (hESC-MSCs), but also describes the immunomodulative effects of hESC-MSCs in
      vitro and in vivo for a carbon tetrachloride (CCl(4))-induced liver inflammation
      model. METHODS: Undifferentiated hESCs were treated with Rho-associated kinase
      (ROCK) inhibitor and induced to fibroblast-looking cells. These cells were tested
      for their surface markers and multilineage differentiation capability. Further
      more, we analyzed their immune characteristics by mixed lymphocyte reactions
      (MLRs) and animal experiments. RESULTS: hESC-MSCs show a homogenous fibroblastic
      morphology that resembles bone marrow-derived MSCs (BM-MSCs). The cell markers
      and differentiation potential of hESC-MSCs are also similar to those of BM-MSCs.
      Unlike their original cells, hESC-MSCs possess poor immunogenicity and can
      survive and be engrafted into a xenogenic immunocompetent environment.
      CONCLUSIONS: The hESC-MSCs demonstrate strong inhibitory effects on lymphocyte
      proliferation in vitro and anti-inflammatory infiltration properties in vivo.
      This study offers information essential to the applications of hESC-MSC-based
      therapies and evidence for the therapeutic mechanisms of action.

PMID- 21194183
TI  - Gastric duplication cyst lined by pseudostratified columnar ciliated epithelium:
      a case report and literature review.
AB  - Gastric duplication cyst (GDC) lined by pseudostratified columnar ciliated
      epithelium (PCCE) is an uncommon lesion stemming from a foregut developmental
      malformation. Its clinical and radiological presentation is usually nonspecific.
      In this study, we reported a 76-year-old man who presented with an incidentally
      found perigastric mass. An exploratory laparotomy revealed a non-communicating
      cyst below the gastroesophageal junction, measuring 4 cm*4 cm in size.
      Microscopically, the gastric cyst was lined merely by PCCE. Although rare, GDC
      lined by PCCE should be included in the differential diagnosis of gastric wall
      masses. Surgical intervention is warranted in patients who have clinical
      symptoms, or who are aged more than 50 years.

PMID- 21194184
TI  - A multiple-dose pharmacokinetics of polyethylene glycol recombinant human
      interleukin-6 (PEG-rhIL-6) in rats.
AB  - Radiation therapy has been widely applied in cancer treatment. However, it often
      causes thrombocytopenia (deficiency of white blood cells) as an adverse effect.
      Recombinant human interleukin-6 (rhIL-6) has been found to be a very effective
      way against this thrombocytopenia, but IL-6 has low stability in blood, which
      reduces its efficacy. To increases the stability and half-life of rhIL-6, it was
      modified by polyethylene glycol (PEG). The pharmacokinetics and the tissue
      distribution of PEG-rhIL-6 labeled with (125)I were examined after subcutaneous
      injection in rats. The pharmacokinetic pattern of PEG-rhIL-6 was defined with
      linear-kinetics, and we fitted a one-compartment model with half-lives of 10.44
      11.37 h (absorption, t(1/2Ka)) and 19.77-21.53 h (elimination, t(1/2Ke)), and
      peak concentrations at 20.51-21.96 h (t(peak)) in rats. Half-lives and t(peak) of
      PEG-rhIL-6 were longer than those of rhIL-6 previously reported. In the present
      study, for deposition of PEG-rhIL-6 in rats, the tissue distribution examination
      showed that blood was the major organ involved, rather than liver. However, as to
      the elimination of PEG-rhIL-6, the major organ was the kidney. The excretion
      fraction of the injection dose recovered from urine was 23.32% at 192 h after
      subcutaneous administration. Less than 6% of PEG-rhIL-6 was eliminated via the
      feces at 192 h. These results indicate that PEG-rhIL-6 is a good candidate drug
      formulation for patients with cancer.

PMID- 21194185
TI  - Methotrexate ameliorates pristane-induced arthritis by decreasing IFN-gamma and
      IL-17A expressions.
AB  - OBJECTIVE: This study was carried out to test the effects of methotrexate (MTX)
      and black seed oil (BSO) on pristane-induced arthritis (PIA) in rats. METHODS:
      Inbred dark agouti (DA) rats were induced by a single subcutaneous injection of
      pristane, and then treated with MTX or BSO. Arthritis severity was evaluated
      macroscopically and microscopically. Plasma nitric oxide (NO) concentration was
      determined by the Griess method and cytokine mRNA expression in the spleen was
      detected by the real-time reverse transcription-polymerase chain reaction (RT
      PCR). RESULTS: The clinical arthritis severity was decreased after MTX treatment,
      while the BSO groups did not show significant changes compared with the disease
      group. The plasma NO level of the MTX group was significantly decreased compared
      with the disease group, but the BSO groups showed no difference from the disease
      group in plasma NO levels. The interferon-gamma (IFN-gamma) and interleukin-17A
      (IL-17A) mRNA expressions in the spleens were significantly decreased in the MTX
      group, but only showed a declining trend in the BSO groups compared with the
      disease group. Neither MTX nor BSO had an effect on the mRNA expressions of IL-4,
      transforming growth factor beta (TGF-beta), and tumor necrosis factor-alpha (TNF
      alpha) in the spleen. CONCLUSIONS: MTX, but not BSO, can reduce the arthritis
      severity and decrease the mRNA expressions of IFN-gamma and IL-17A in pristane
      induced arthritis of rats.

PMID- 21194186
TI  - Eucommia ulmoides Oliv. antagonizes H2O2-induced rat osteoblastic MC3T3-E1
      apoptosis by inhibiting expressions of caspases 3, 6, 7, and 9.
AB  - Eucommia ulmoides Oliv. (EuO), also known as Duzhong, native to China, has been
      reported to have antioxidative function, but its cellular mechanism is not fully
      examined yet. We investigated inhibitory effects of EuO leaf ethanol extracts on
      H(2)O(2)-induced apoptosis in rat osteoblastic MC3T3-E1 cells and underlying
      mechanisms. Locally-grown Duzhong leaves were extracted with ethanol. MC3T3-E1
      cells were treated with EuO (6.25, 12.5, 25, 50, and 100 ug/ml) for 24 h, and
      then H(2)O(2) (800 umol/L) for an additional 24 h. Cell survival rate, percentage
      of apoptosis, and expressions of caspases 3, 6, 7, and 9 were examined using 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay,
      microscopic analysis, Western blotting, and reverse transcription polymerase
      chain reaction (RT-PCR). The final EuO leaf ethanol extract powder was detected
      to contain caffeotannic acid at 58 mg/g and geniposide at 3.45 mg/g by high
      performance liquid chromatography (HPLC). EuO remarkably restrained cell
      oxidative damage and increased cell survival rate in a dose-dependent manner: 0
      ug/ml, 0.21; 6.25 ug/ml, 0. 28; 12.5 ug/ml, 0.31; 25 ug/ml, 0.48; 50 ug/ml, 0.54;
      and 100 ug/ml, 0.66 (P<0.05), with the half-effective concentration being around
      25 ug/ml. MTT results were confirmed by microscopic analysis. Western blotting
      and RT-PCR analyses showed that the expressions of caspases 3, 6, 7, and 9 were
      significantly decreased in the EuO-treated cells compared with the control (EuO-
      and H(2)O(2)-free) (P<0.05), with the half-effective concentration of EuO ranging
      from 12.5 to 25 ug/ml. We conclude that the ethanol-extracted EuO leaf extracts
      promoted the growth of MC3T3-E1 cells, and suppressed the H(2)O(2)-induced
      apoptosis in a rat MC3T3-E1 osteogenic cell model, likely due to the inhibition
      of caspases' activities. The results indicate that EuO is a potent antioxidant,
      which may contribute to its many cellular protective functions, including the
      promotion of bone growth.

PMID- 21194188
TI  - Fusion expression of pedA gene to obtain biologically active pediocin PA-1 in
      Escherichia coli.
AB  - Two heterologous expression systems using thioredoxin (trxA) as a gene fusion
      part in Escherichia coli were developed to produce recombinant pediocin PA-1.
      Pediocin PA-1 structural gene pedA was isolated from Pediococcus acidilactici
      PA003 by the method of polymerase chain reaction (PCR), then cloned into vector
      pET32a(+), and expressed as thioredoxin-PedA fusion protein in the host strain E.
      coli BL21 (DE3). The fusion protein was in the form of inclusion body and was
      refolded before purification by nickel-iminodiacetic acid (Ni-IDA) agarose resin
      column. Biological activity of recombinant pediocin PA-1 was analyzed after
      cleavage of the fusion protein by enterokinase. Agar diffusion test revealed that
      512-arbitrary unit (AU) recombinant pediocin PA-1 was obtained from 1 ml culture
      medium of E. coli (pPA003PED1) using Listeria monocytogenes as the indicator
      strain. Thioredoxin-PedA fusion gene was further cloned into pET20b(+).
      Thioredoxin-PedA fusion protein was detected in both the periplasmic and
      cytoplasmic spaces. The recombinant pediocin PA-1 from the soluble fraction
      attained 384 AU from 1 ml culture medium of E. coli (pPA003PED2). Therefore,
      biologically active pediocin PA-1 could be obtained by these two hybrid gene
      expression methods.

PMID- 21194187
TI  - Cell-specific expression and immunolocalization of nitric oxide synthase isoforms
      and the related nitric oxide/cyclic GMP signaling pathway in the ovaries of
      neonatal and immature rats.
AB  - OBJECTIVE: The present study is designed to investigate the cellular expressions
      and immunolocalizations of three different nitric oxide synthase (NOS) isoforms
      and the related nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling
      pathway in the ovaries of neonatal and immature rats. METHODS: The ovaries were
      obtained from ICR (Institute for Cancer Research) female Sprague-Dawley rats at
      postnatal days 1, 5, 7, 10, and 19. Then we carried out the histologic
      examination, immunohistochemistry, measurement of NOS activity, and modifications
      within the NO/cGMP pathway. RESULTS: During postnatal days 1, 5, 7, 10, and 19,
      all three isoforms of NOS were mainly localized to the oocytes and expressed as a
      gradual increase in granulosa cells and theca cells within the growing follicle.
      The ovarian total NOS activities and NO levels were increased at postnatal days 7
      and 10 compared with other days. CONCLUSIONS: Our findings suggest that the
      locally produced NO and the NO/NOS signaling systems are involved in the
      follicular development to puberty.

PMID- 21194190
TI  - Generation of random numbers on graphics processors: forced indentation in silico
      of the bacteriophage HK97.
AB  - The use of graphics processing units (GPUs) in simulation applications offers a
      significant speed gain as compared to computations on central processing units
      (CPUs). Many simulation methods require a large number of independent random
      variables generated at each step. We present two approaches for implementation of
      random number generators (RNGs) on a GPU. In the one-RNG-per-thread approach, one
      RNG produces a stream of random numbers in each thread of execution, whereas the
      one-RNG-for-all-threads method builds on the ability of different threads to
      communicate, thus, sharing random seeds across an entire GPU device. We used
      these approaches to implement Ran2, Hybrid Taus, and Lagged Fibonacci algorithms
      on a GPU. We profiled the performance of these generators in terms of the
      computational time, memory usage, and the speedup factor (CPU time/GPU time).
      These generators have been incorporated into the program for Langevin simulations
      of biomolecules fully implemented on the GPU. The ~250-fold computational speedup
      on the GPU allowed us to carry out single-molecule dynamic force measurements in
      silico to explore the mechanical properties of the bacteriophage HK97 in the
      experimental subsecond time scale. We found that the nanomechanical response of
      HK97 depends on the conditions of force application, including the rate of change
      and geometry of the mechanical perturbation. Hence, using the GPU-based
      implementation of RNGs, presented here, in conjunction with Langevin simulations,
      makes it possible to directly compare the results of dynamic force measurements
      in vitro and in silico.

PMID- 21194189
TI  - Effect of terminal locations of pods on biomass production and 13C partitioning
      in a fasciated stem soybean Shakujo.
AB  - This study addresses the hypothesis that stagnation of soybean yield on the farm
      can be improved by selection of a physiological trait favoring carbon assimilate
      partitioning to terminally placed pods versus genotypes having axillary pods at
      close plant spacing. (13)C was fed to source-sink units comprising a leaf,
      axillary/terminal pods, and petioles at upper and lower positions of the stem
      axis in two soybean cultivars, namely Shakujo and Enrei, at different densities
      of populations. The cultivars differ significantly in architecture, Shakujo
      bearing a few hundreds of pods in close succession to one another in a terminally
      placed raceme, in contrast to Enrei having axillary racemes. Pod yield per plant
      was higher in Enrei than in Shakujo at low density, but Shakujo out-yielded Enrei
      at close spacing. Population density decreased yield per plant and altered the
      pattern of assimilate partitioning significantly within the plants for both
      varieties. At high density more assimilates moved to the upper parts at the cost
      of the lower parts. The terminally placed pods of Shakujo were advantaged to
      receive assimilates under density stress. No benefit was accrued to pod filling
      of Enrei, however, under this condition.

PMID- 21194191
TI  - Cooperative binding and stabilization of the medicinal pigment curcumin by
      diamide linked gamma-cyclodextrin dimers: a spectroscopic characterization.
AB  - Diamide linked gamma-cyclodextrin (gamma-CD) dimers are used to capture curcumin
      and suppress its decomposition in water. In this study, succinamide and urea
      linked gamma-CD dimers joined through the C6(A) carbon on each gamma-CD are used.
      The gamma-CD dimers, 66gammaCD(2)su and 66gammaCD(2)ur, show a remarkable ability
      to suppress the decomposition of curcumin and extend its half-life from less than
      30 min to greater than 16 h. The 1:1 association of curcumin with 66gammaCD(2)su
      and 66gammaCD(2)ur has high stability constants of 8.7 * 10(6) M(-1) and 2.0 *
      10(6) M(-1), respectively. In addition, 2D (1)H NOESY NMR results show specific
      hydrogen interactions in the association of curcumin with 66gammaCD(2)su and
      66gammaCD(2)ur, consistent with the cooperative binding of curcumin by both gamma
      CD annuli of 66gammaCD(2)su and 66gammaCD(2)ur. The interactions between curcumin
      in the linked gamma-CD dimers and surfactant micelles were studied using
      fluorescence spectroscopy. While linked gamma-CD dimer-bound curcumin has a
      negligible fluorescence quantum yield, a significant increase in fluorescence
      intensity (Phi(fl) > 2%) in the presence of micelles suggests that curcumin is
      delivered to the micelle. The overall results indicate that the diamide linked
      gamma-CD dimers are highly promising systems for curcumin delivery in vivo due to
      effective curcumin stabilization.

PMID- 21194192
TI  - On the formation of resonantly stabilized C5H3 radicals--a crossed beam and ab
      initio study of the reaction of ground state carbon atoms with vinylacetylene.
AB  - The formation of polycyclic aromatic hydrocarbons in combustion environments is
      linked to resonance stabilized free radicals. Here, we investigated the reaction
      dynamics of ground state carbon atoms, C((3)P(j)), with vinylacetylene at two
      collision energies of 18.8 kJ mol(-1) and 26.4 kJ mol(-1) employing the crossed
      molecular beam technique leading to two resonantly stabilized free radicals. The
      reaction was found to be governed by indirect scattering dynamics and to proceed
      without an entrance barrier through a long-lived collision complex to reach the
      products, n- and i-C(5)H(3) isomers via tight exit transition states. The
      reaction pathway taken is dependent on whether the carbon atom attacks the pi
      electron density of the double or triple bond, both routes have been compared to
      the reactions of atomic carbon with ethylene and acetylene. Electronic
      structure/statistical theory calculations determined the product branching ratio
      to be 2:3 between the n- and i-C(5)H(3) isomers.

PMID- 21194193
TI  - TiO2- and BaTiO3-assisted photocatalytic degradation of selected chloroorganic
      compounds in aqueous medium: correlation of reactivity/orientation effects of
      substituent groups of the pollutant molecule on the degradation rate.
AB  - Investigation of the photocatalytic activity of BaTiO(3), a perovskite wideband
      gap semiconductor has been done in comparison with a widely used photocatalyst
      TiO(2) for the degradation of 4-chlorophenol (4-CP), 4-chloroaniline (4-CA), 3,4
      dichloronitrobenzene (3,4-DCNB), and 2,4,5-trichlorophenol (2,4,5-TCP).
      BaTiO(3)/TiO(2) nanoparticles were prepared by gel-to-crystalline conversion
      method. BaTiO(3) has exhibited better catalytic efficiency and process efficiency
      compared with TiO(2) in most of the cases. The present research focuses mainly on
      two aspects: first the photocatalytic activity of BaTiO(3), as there are very few
      reports in the literature, and second the reactivity/orientation effects of
      substituent groups of the pollutant molecules on the degradation rate. The above
      chloroorganic compounds have at least one chlorine substituent in common, along
      with other functional groups such as -OH, -NH(2), and -NO(2). Furthermore, the
      effect of electron acceptors and pH on the rate of degradation is presented. The
      reactions follow first-order kinetics. The degradation reaction was followed by
      UV-vis, IR, and GC-MS spectroscopic techniques. On the basis of the
      identification of the intermediates, a probable degradation reaction mechanism
      has been proposed for each compound.

PMID- 21194194
TI  - Delocalization of positive charge in pi-stacked multi-benzene rings in
      multilayered cyclophanes.
AB  - In the present study, delocalization of a positive charge in pi-stacked multi
      benzene rings in multilayered para- and meta-cyclophanes, in which benzene rings
      are connected by propyl chains to form a chromophore array with the face-to-face
      structure, was investigated by means of transient absorption spectroscopy during
      the pulse radiolysis using dichloroethane as a solvent. The local excitation and
      charge resonance (CR) bands were successfully observed. It was revealed that the
      CR band shifted to the longer wavelength side with the number of the benzene
      rings. The stabilization energy estimated from the peak position of the CR band
      showed the efficient charge delocalization over the cyclophanes. Furthermore, the
      CR bands showed the slight spectral change attributable to the change in
      distribution of the conformers. The substantially long lifetime of the CR band
      can be explained on the basis of the smaller charge distribution on the outer
      layers of the multilayered cyclophanes.

PMID- 21194195
TI  - Petroleum hydrocarbon biodegradation under seasonal freeze-thaw soil temperature
      regimes in contaminated soils from a sub-Arctic site.
AB  - Several studies have shown that biostimulation in ex situ systems such as
      landfarms and biopiles can facilitate remediation of petroleum hydrocarbon
      contaminated soils at sub-Arctic sites during summers when temperatures are above
      freezing. In this study, we examine the biodegradation of semivolatile (F2: C10
      C16) and nonvolatile (F3: C16-C34) petroleum hydrocarbons and microbial
      respiration and population dynamics at post- and presummer temperatures ranging
      from -5 to 14  degrees C. The studies were conducted in pilot-scale tanks with
      soils obtained from a historically contaminated sub-Arctic site in Resolution
      Island (RI), Canada. In aerobic, nutrient-amended, unsaturated soils, the F2
      hydrocarbons decreased by 32% during the seasonal freeze-thaw phase where soils
      were cooled from 2 to -5  degrees C at a freezing rate of -0.12  degrees C d(-1)
      and then thawed from -5 to 4  degrees C at a thawing rate of +0.16  degrees C d(
      1). In the unamended (control) tank, the F2 fraction only decreased by 14% during
      the same period. Biodegradation of individual hydrocarbon compounds in the
      nutrient-amended soils was also confirmed by comparing their abundance over time
      to that of the conserved diesel biomarker, bicyclic sesquiterpanes (BS). During
      this period, microbial respiration was observed, even at subzero temperatures
      when unfrozen liquid water was detected during the freeze-thaw period. An
      increase in culturable heterotrophs and 16S rDNA copy numbers was noted during
      the freezing phase, and the (14)C-hexadecane mineralization in soil samples
      obtained from the nutrient-amended tank steadily increased. Hydrocarbon degrading
      bacterial populations identified as Corynebacterineae- and Alkanindiges-related
      strains emerged during the freezing and thawing phases, respectively, indicating
      there were temperature-based microbial community shifts.

PMID- 21194196
TI  - Predicting hormetic effects of ionic liquid mixtures on luciferase activity using
      the concentration addition model.
AB  - The concept of hormesis has generated considerable interest within the
      environmental and toxicological communities over the past decades. However,
      toxicological evaluation and prediction of hormesis in mixtures are challenging
      and only just unfolding. The hormetic effects of ten ionic liquids (ILs), singly
      and in mixtures in the ratios of their individual EC50, EC10, EC0, and ECm
      (maximal stimulatory effect concentration), on luciferase luminescence were
      determined by using microplate toxicity analysis. There was good agreement
      between the effects observed and predicted by concentration addition (CA) for all
      four mixtures. This evidence supports the use of CA model as a default approach
      for assessing the combined effect of chemicals at the molecular level. Focusing
      on the selected points of the concentration-response curves (CRCs) of mixtures,
      the mixtures of IL chemicals mixed at concentrations that individually showed
      stimulatory effects could produce inhibitory or no effects, and the mixture of IL
      chemicals mixed at concentrations that individually showed no effects could
      produce significant inhibitory effect. The three interesting phenomena in mixture
      hormesis may have important implications for current risk assessment practices.

PMID- 21194197
TI  - Chemometrics-assisted fluorimetry for the rapid and selective determination of
      heavy polycyclic aromatic hydrocarbons in contaminated river waters and activated
      sludges.
AB  - The most concerned polycyclic aromatic hydrocarbons (PAHs) benzo[a]pyrene,
      dibenz[a,h]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene and
      benz[a]anthracene were simultaneously determined in the presence of other 10
      interfering PAHs, applying second-order multivariate calibration to the data
      obtained with a flow-through optosensor interfaced to a fast-scanning
      spectrofluorimeter. Using a sample volume of 2.5 mL, detection limits in the
      range 5-115 ng L(-1) were obtained in interfering samples, with a sample
      frequency of ca. 15 samples per hour, and with a minimum use of organic solvents,
      competing very favorably with chromatographic methods. The significance of this
      study lies in the solution of the quantitative analysis problem of six PAHs in
      real matrices of unknown composition. The unfolded partial least-squares/residual
      bilinearization (U-PLS/RBL) algorithm showed the best performance in resolving
      the complex studied system.

PMID- 21194198
TI  - Pyrene biodegradation in an industrial soil exposed to simulated rhizodeposition:
      how does it affect functional microbial abundance?
AB  - Rhizodeposition is an important biogeochemical process for the phytoremediation
      of contaminated substrates. This study investigated the effects of various
      rhizodeposition components from celery (Apium graveolens) on pyrene
      biodegradation and microbial abundance in a long-term contaminated soil. Batch
      microcosms simulating in situ contaminated soil were amended with lipophilic
      extract, water-soluble extract, or debris from celery root to mimic plant
      rhizodeposition within 70 days. Soil was intermittently analyzed for pyrene
      concentration and target gene abundance estimated by real-time PCR. Lipophilic
      extract was the major simulated rhizodeposit enhancing pyrene biodegradation,
      while water-soluble extract stimulated microbial growth most efficiently. The
      relative abundance of total polycyclic aromatic hydrocarbon (PAH) degraders was
      enhanced by lipophilic extract but inhibited by the other two rhizodeposits,
      indicating that these components exerted different selective pressures on PAH
      degrader community. Moreover, PAH catabolic pathway may involve in the pollutant
      detoxification and fatty acid metabolism by microorganisms, which were also
      affected by rhizodeposition. These results provide insights into plant-microbe
      interactions responsible for PAH biodegradation and offer opportunities to
      facilitate PAH phytoremediation in industrial sites.

PMID- 21194200
TI  - Fabrication of patterned polymer nanowire arrays.
AB  - A method for the large-scale fabrication of patterned organic nanowire (NW)
      arrays is demonstrated by the use of laser interference patterning (LIP) in
      conjunction with inductively coupled plasma (ICP) etching. The NW arrays can be
      fabricated after a short ICP etching of periodic patterns produced through LIP.
      Arrays of NWs have been fabricated in UV-absorbent polymers, such as PET
      (polyethylene terephthalate) and Dura film (76% polyethylene and 24%
      polycarbonate), through laser interference photon ablation and in UV transparent
      polymers such as PVA (polyvinyl acetate) and PP (polypropylene) through laser
      interference lithography of a thin layer of photoresist coated atop the polymer
      surface. The dependence of the structure and morphology of NWs as a function of
      initial pattern created by LIP and the laser energy dose in LIP is discussed. The
      absence of residual photoresist atop the NWs in UV-transparent polymers is
      confirmed through Raman spectroscopy.

PMID- 21194201
TI  - Tunneling-induced spectral broadening of a single atom in a three-dimensional
      optical lattice.
AB  - We have investigated the spectral broadening in the near-resonance fluorescence
      spectrum of a single rubidium atom trapped in a three-dimensional (3D) optical
      lattice in a strong Lamb-Dicke regime. Besides the strong Rayleigh peak, the
      spectrum exhibited weak Stokes and anti-Stokes Raman sidebands. The line width of
      the Rayleigh peak for low potential depths was well explained by matter-wave
      tunneling between the first-two lowest vibrational states of 3D anisotropic
      harmonic potentials of adjacent local minima of the optical lattice.

PMID- 21194202
TI  - Anion responsive TTF-appended calix[4]arenes. Synthesis and study of two
      different conformers.
AB  - Two new cone- and 1,3-alternate-calix[4]arenes (cone-1 and 1,3-alt-1), bearing
      four modified TTF (tetrathiafulvalene) substituents on the upper rim, have been
      synthesized. The binding ability of these two sets of conformers for various
      anions, including F(-), Cl(-), Br(-), I(-), PF6(-), ClO4(-), HSO4(-), CH3COO(-),
      H2PO4(-), and HP2O7(3-), was tested in organic media by monitoring the changes in
      their UV/vis and (1)H NMR spectra as a function of added anion, as well as via
      cyclovoltammetry (CV) (all anions studied as their respective TBA salts). On the
      basis of the present findings, we propose that incorporation of four TTF units
      within an overall calix[4]arene-based recognition framework produces a
      preorganized receptor system that displays a modest preference for the
      pyrophosphate (HP2O7(3-)) anion.

PMID- 21194203
TI  - Molecular dynamics studies of transportan 10 (tp10) interacting with a POPC lipid
      bilayer.
AB  - We performed a series of molecular dynamics simu lations to study the nature of
      interactions between transportan 10 (tp10) and a zwitterionic POPC bilayer. Tp10
      is an amphipathic cell-penetrating peptide with a net positive charge of +5 and
      is known to adopt an alpha-helical secondary structure on the surface of POPC
      membranes. The study showed that tp10 preferentially binds to the membrane
      surface with its hydrophobic side facing the hydrophobic lipid core. Such
      orientation allows Lys residues, with positively charged long side chains, to
      stay in the polar environment during the insertion process. The simulations
      revealed that the Lys-phosphate salt bridge is a key factor in determining the
      orientation of the peptide in the interfacial region as well as in stabilizing
      the peptide-membrane interaction. The electrostatic attraction between Lys and
      phosphate groups is also believed to be the main bottleneck for the translocation
      of tp10 across the membrane.

PMID- 21194204
TI  - Plasmonic dye-sensitized solar cells using core-shell metal-insulator
      nanoparticles.
AB  - We present an investigation into incorporating core-shell Au-SiO(2) nanoparticles
      into dye-sensitized solar cells. We demonstrate plasmon-enhanced light
      absorption, photocurrent, and efficiency for both iodide/triiodide electrolyte
      based and solid-state dye-sensitized solar cells. Our spectroscopic investigation
      indicates that plasmon-enhanced photocarrier generation competes well with
      plasmons oscillation damping with in the first tens of femtoseconds following
      light absorption.

PMID- 21194205
TI  - Mutagenicity of PFOA in mammalian cells: role of mitochondria-dependent reactive
      oxygen species.
AB  - Mutagenicity is often a prerequisite to the development of malignancy. Evidences
      have shown that exposure to perfluorooctanoic acid (PFOA) results in various
      cancer inductions. However, whether any mutagenic base exists is still puzzling.
      In the present study, we exposed exponentially growing AL cells to PFOA and
      assayed the cells for survival, mutation induction, and caspase-3/7, -9
      activities. Mitochondrial-DNA deficient human-hamster hybrid (rho(0) AL) cells
      and reactive oxygen species (ROS) inhibitor were used to elucidate the possible
      mechanism. Our results showed that treatment of AL cells with PFOA for 16 days
      induced significant mutagenic effects together with the increment of ROS,
      superoxide anions (O2(.-)), and nitrogen oxide (NO) levels, while treatment of
      rho(0) AL cells did not have much change. Concurrent treatment of AL cells with
      ROS inhibitor significantly decreased the mutagenic potential of PFOA. In
      addition, caspase activities in AL cells were increased by PFOA exposure and
      suppressed by ROS/RNS (reactive oxygen/nitrogen species) inhibitors. Our results
      suggest that exposure to PFOA lead to mutagenicity induction in AL cells, and
      mitochondria-dependent ROS plays an important role in this process. This provides
      a direct base for PFOA mediated cancer induction.

PMID- 21194206
TI  - Sorption of organic chemicals to soil organic matter: influence of soil
      variability and pH dependence.
AB  - For modeling the sorption of organic compounds in soils it is typically assumed
      that the organic carbon/water partitioning coefficient (Koc) of neutral organic
      chemicals can be treated as a constant property that remains unaffected by the
      type of soil organic matter as well as pH in the soil solution. Here the validity
      of these assumptions is evaluated with a large and diverse experimental data set
      of our own and literature data. To this end sorption experiments with 3 different
      soils and one peat were carried out using a column method. Differences in log Koc
      at pH values of 4.5 and 7.2 were on average <0.06 log units for 60 chemicals on
      Pahokee Peat. This result indicates that protonation/deprotonation of carboxylic
      groups in humic matter has no significant influence on sorption. The soil-to-soil
      variability of Koc was within factor of 3 regardless of the type of chemicals.
      The Pahokee Peat standard from the International Humic Substances Society appears
      to represent Koc in solid soil organic matter from different origins with an
      accuracy of +/-0.23 log units (root-mean-square error). The comparison of the
      sorption data in Pahokee Peat with literature sorption data from the air in
      hydrated humic and fulvic acids suggested that the thermodynamic cycle for
      converting sorption data between air and water is applicable provided that for
      small, highly polar chemicals an additional water phase in the hydrated organic
      matter is considered.

PMID- 21194207
TI  - Formation of organic crystalline nanopillar arrays and their application to
      organic photovoltaic cells.
AB  - To enhance the performance of organic photovoltaic (OPV) cells, preparation of
      organic nanometer-sized pillar arrays is fascinating because a significantly
      large area of a donor/acceptor heterointerface having continuous conduction path
      to both anode and cathode electrodes can be realized. In this study, we grew
      cupper phthalocyanine (CuPc) crystalline nanopillar arrays by conventional
      thermal gradient sublimation technique using a few-nanometer-sized trigger seeds
      composed of a CuPc and 3,4,9,10-perylene-tetracarboxylic-dianhydride (PTCDA)
      stacked layer. We optimized the pillar density by tuning crystal growth condition
      in order to apply it to OPV cells.

PMID- 21194208
TI  - Photoelectrochemical characterization of nanocrystalline thin-film Cu2ZnSnS4
      photocathodes.
AB  - Cu2ZnSnS4 (CZTS) nanocrystals, synthesized by a hot injection solution method,
      have been fabricated into thin films by dip-casting onto fluorine doped tin oxide
      (FTO) substrates. The photoresponse of the CZTS nanocrystal films was evaluated
      using absorbance measurements along with photoelectrochemical methods in aqueous
      electrolytes. Photoelectrochemical characterization revealed a p-type
      photoresponse when the films were illuminated in an aqueous Eu(3+) redox
      electrolyte. The effects of CZTS stoichiometry, film thickness, and low
      temperature annealing on the photocurrents from front and back illumination
      suggest that the minority carrier diffusion and recombination at the back contact
      (via reaction of photogenerated holes with Eu(2+) produced from photoreduction by
      minority carriers) are the main loss mechanisms in the cell. Low-temperature
      annealing resulted in significant increases in the photocurrents for films made
      from both Zn-rich and stoichiometric CZTS nanocrystals.

PMID- 21194210
TI  - Predicting sorption of pesticides and other multifunctional organic chemicals to
      soil organic carbon.
AB  - Chemicals of current environmental concern are often multifunctional and more
      polar and more complex than classical pollutants such as polychlorinated
      biphenyls (PCB) or polycyclic aromatic hydrocarbons (PAH). Traditional models for
      predicting the partitioning in the environment such as group contribution methods
      or correlations with octanol-water partitioning cannot be expected to work well
      for such complex chemicals. In contrast, poly parameter Linear Free Energy
      Relationships (pp-LFERs) have been proven to describe partitioning of polar and
      nonpolar chemicals in all kinds of sorbing systems. Here, a pp-LFER model for
      soil-water partitioning was calibrated with data for 79 polar and nonpolar
      compounds that cover a very wide range of the relevant intermolecular
      interactions. The data set used for the model calibration in this work is more
      diverse and covers a wider range of the chemical space than other pp-LFERs
      published so far. Subsequently, the experimental data for about 50 pesticides and
      pharmaceuticals -not involved in the model calibration- were used as independent
      validation of this new calibrated model. The model performs well with a standard
      error of 0.25 log units for fitting the calibration data and with a root-mean
      square error of 0.4 log units for the pesticides and pharmaceuticals. The
      validation with the independent data set for pesticides and pharmaceuticals also
      shows that the pp-LFER model reported here performs better compared to earlier
      published pp-LFER models and to the traditional log Kow correlation.

PMID- 21194209
TI  - Nucleophilic ring-opening of epoxide and aziridine acetates for the
      stereodivergent synthesis of beta-hydroxy and beta-amino gamma-lactams.
AB  - A highly regio- and stereoselective synthesis of novel beta,gamma-disubstituted
      gamma-lactams with either an anti or syn relative configuration was developed
      from readily available epoxide and aziridine acetates. The key steps include the
      regio- and diastereocontrolled nucleophilic ring-opening of these three-membered
      heterocycles followed by mild reductive cyclization of the gamma-azido ester
      intermediate. The method was also extended to an asymmetric synthesis of (4R,5S)
      4-hydroxy-5-phenylpyrrolidin-2-one from a chiral epoxide acetate. The main
      features of this versatile synthesis of functionalized gamma-lactams include the
      involvement of inexpensive reagents and mild conditions together with high
      chemical efficiency.

PMID- 21194211
TI  - Geoelectrical imaging of hyporheic exchange and mixing of river water and
      groundwater in a large regulated river.
AB  - Hyporheic mixing and surface water-groundwater interactions are critical
      processes in aquatic environments. Yet, there is a lack of methods for assessing
      the spatial extent and distribution of these mixing zones. This study applied
      time-lapse electrical resistivity (ER) imaging in a 60-m wide and 0.7-m deep
      alluvial river whose stage periodically varied by 0.7 m due to dam operations to
      assess dynamic hyporheic mixing and surface water-groundwater interactions.
      Sixteen channel-spanning repeat ER tomograms (2D sections) over one flood cycle
      captured the dynamic ER distribution. We mapped a laterally discontinuous
      hyporheic zone, which had mainly river water circulating through it, several
      meters into the bed. Underneath the hyporheic zone was a transitional mixing zone
      intermittently flushed by mixing river water and deep groundwater. Minimally
      mixed groundwater dominated the deepest areas. ER imaging allows for unraveling
      hyporheic and deep mixing zone dynamics in large regulated rivers.

PMID- 21194212
TI  - QuEChERS multiresidue method validation and mass spectrometric assessment for the
      novel anthranilic diamide insecticides chlorantraniliprole and cyantraniliprole.
AB  - The gas-phase dissociation reactions of chlorantraniliprole (Rynaxypyr) and
      cyantraniliprole (Cyazypyr) have been studied in triple-quadrupole, ion trap, and
      orbitrap mass spectrometers equipped with electrospray and desorption
      electrospray ion sources, revealing the formation of odd-electron fragment ions,
      the structures of which were elucidated. The odd-electron fragments were
      unusually abundant, and their formation is proposed to occur via a tricyclic
      intermediate. The applicability of the QuEChERS multiresidue method for the
      quantitation of chlorantraniliprole and cyantraniliprole was also assessed in
      this study. Four matrices representative of oily, watery, acidic, and dry crop
      groups were tested, with a targeted limit of quantitation (LOQ) of 0.01 mg/kg.
      Average recoveries ranged between 87 and 107%, with relative standard deviations
      (RSD) of <= 8%. Linear calibration functions with correlation coefficients r >
      0.99 were obtained. The study provides an expansion of the QuEChERS method to
      include anthranilic diamides and a mass spectrometric assessment for these two
      novel agrochemical active ingredients.

PMID- 21194213
TI  - Simple route to enhanced photocatalytic activity of p25 titanium dioxide
      nanoparticles by silica addition.
AB  - Silica doped TiO2(P25) nanoparticles are tested for its photocatalytic activity
      in the degradation of bacteriophage MS2. During our studies it was found that
      treatment of TiO2(P25) in the glass flasks sealed with silicone grease resulted
      in a significant improvement in the catalytic activity of the titania. Further
      improvement can be made by the purposeful reaction of TiO2(P25) with 2.5 wt %
      silica. This non in situ method of incorporating silica to TiO2(P25)
      nanoparticles is tested for their role in killing of viruses, and it is found
      that the rate constant is three times higher to kill viruses with the addition of
      silica. BET measurements show no significant change/increase in the surface area
      of silica doped TiO2(P25)-SiO2, compared to the undoped TiO2(P25). Further
      studies show that the addition of silica increases the adsorption of viruses onto
      the catalyst. There is a significant difference in the activity of the TiO2(P25)
      SiO2 samples in the presence of methanol, supporting the notion that hydroxide
      radical (HO.) is responsible for the antiviral action. The TiO2(P25)-SiO2 either
      produces more HO. than non silica-doped material, or the enhanced adsorption of
      MS2 to the catalyst results in greater exposure to the HO., or both mechanisms
      may work in concert. XPS studies suggest the formation of silica species on the
      surface of the TiO2(P25), while UV-visible spectroscopy suggests that the
      presence of the silica results in a small increase in the measured band gap. We
      suggest that the enhanced catalytic activity is a result of increased adsorption
      and/or band bending which can occur at the interface within TiO2(P25)-SiO2. One
      result of this would be a reduction of the electron-hole recombination, the
      formation of a greater concentration of OH., and hence an improved catalytic
      performance.

PMID- 21194214
TI  - NMR insight into the supramolecular structure of daunorubicin loaded polymer
      nanoparticles.
AB  - Nuclear magnetic resonance (NMR) spectroscopy has been employed for structural
      characterization of daunorubicin-loaded poly(butylcyanoacrylate) nanoparticles.
      Measurements of the nuclear relaxation times (T(1)) and application of diffusion
      ordered spectroscopy (DOSY), obtained through pulsed field gradient (PFG) NMR
      experiments, have been performed to determine the supramolecular structure of the
      drug-polymer conjugates and to clarify the mechanisms of drug immobilization in
      the polymer matrix. The results confirm the coexistence of three different
      interaction mechanisms between the drug daunorubicin and the
      poly(butylcyanoacrylate) nanoparticles, viz., (i) drug association with the
      polymer chains through H-bonds and/or dipole-charge interactions, (ii) physical
      entrapment of the drug within the polymer matrix, and (iii) drug adsorption on
      the surface of nanoparticles. The identification of these three different
      interaction mechanisms suggests that drug delivery using the nanoparticle vehicle
      has potential for sustained delivery/release of daunorubicin.

PMID- 21194215
TI  - Effect of high pressure on fully hydrated DPPC and POPC bilayers.
AB  - Enhanced hydrostatic pressure can induce phase transitions in hydrated lipid
      bilayers especially those composed of saturated phospholipids. In this work, the
      phase behavior of fully hydrated DPPC (1,2-dipalmitoyl-sn-glycero-3
      phosphocholine) and POPC (2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine)
      bilayers as a function of pressure up to 3000 atm has been examined in atomic
      detail on time scales of up to 1.0 MUs, using the molecular dynamics simulation
      technique. DPPC bilayers formed a rippled gel-like phase comprising a minor
      disordered fluid-like region and a major ordered gel-like region at 1000 atm, a
      partially interdigitated gel-like phase at 2000 atm, and a gel-like phase with
      most of the lipid acyl chains tilted with respect to the plane of the bilayer at
      3000 atm. POPC bilayers formed a rippled gel-like phase at 1800, 2400, and 3000
      atm. The phase behavior observed for both DPPC and POPC bilayers is in agreement
      with experiment. The simulations provide insight into the structural changes of
      DPPC and POPC bilayers as a function of pressure and demonstrate the ability to
      model biologically relevant lipid systems under high hydrostatic pressure.

PMID- 21194216
TI  - An oxidative dearomatization-induced [5 + 2] cascade enabling the syntheses of
      alpha-cedrene, alpha-pipitzol, and sec-cedrenol.
AB  - Efficient syntheses of alpha-cedrene (1), alpha-pipitzol (2), and sec-cedrenol
      (3) were carried out using a new method, which was inspired by the proposed
      biosynthesis of the tricyclic skeleton of cedrol (12). The key transformation
      begins with the oxidative dearomatization of curcuphenol (5a) followed by an
      intramolecular [5 + 2] cycloaddition of the respective phenoxonium intermediate
      across the tethered olefin. The benzylic stereocenter effectively guides the
      formation of the first two stereocenters during the [5 + 2] reaction. The cascade
      then terminates with the selective incorporation of acetic acid to generate a
      third stereocenter, setting it apart from other previous cationic [5 + 2]
      reactions. The phenolic precursors (5a-h) are constructed from readily available
      salicylaldehydes, either as the racemate (one pot) or as a specific enantiomer
      (four pots) by a modification to our method for the generation of ortho-quinone
      methides (o-QMs).

PMID- 21194217
TI  - Prediction of soil sorption coefficients using model molecular structures for
      organic matter and the quantum mechanical COSMO-SAC model.
AB  - The soil sorption coefficient, K(OC), is an important property affecting the
      environmental fate of organic molecules. Difficulties associated with measuring
      K(OC) have led to many attempts to predict this property, but most rely on
      empirical descriptors for the soil phase determined from correlations with
      measured K(OC) data, and are thereby limited by the data quality and diversity. A
      new method is presented to predict K(OC) for nonionic organic compounds that
      requires only molecular structures. No calibration is performed. Using model
      humic acid (HA) and fulvic acid (FA) molecular structures from the literature,
      the soil organic matter is modeled as an organic solvent composed of HA or FA
      molecules. K(OC) is predicted as an organic solvent-water partition coefficient
      using the quantum mechanics-based model COSMO-SAC. The log K(OC) values for a set
      of 440 diverse, environmentally relevant chemicals are predicted with a root-mean
      square error of 0.84-1.08, depending on which model HA or FA is used.

PMID- 21194218
TI  - Air-water exchange of anthropogenic and natural organohalogens on International
      Polar Year (IPY) expeditions in the Canadian Arctic.
AB  - Shipboard measurements of organohalogen compounds in air and surface seawater
      were conducted in the Canadian Arctic in 2007-2008. Study areas included the
      Labrador Sea, Hudson Bay, and the southern Beaufort Sea. High volume air samples
      were collected at deck level (6 m), while low volume samples were taken at 1 and
      15 m above the water or ice surface. Water samples were taken within 7 m. Water
      concentration ranges (pg L(-1)) were as follows: alpha-hexachlorocyclohexane
      (alpha-HCH) 465-1013, gamma-HCH 150-254, hexachlorobenzene (HCB) 4.0-6.4, 2,4
      dibromoanisole (DBA) 8.5-38, and 2,4,6-tribromoanisole (TBA) 4.7-163. Air
      concentration ranges (pg m(-3)) were as follows: alpha-HCH 7.5-48, gamma-HCH 2.1
      7.7, HCB 48-71, DBA 4.8-25, and TBA 6.4 - 39. Fugacity gradients predicted net
      deposition of HCB in all areas, while exchange directions varied for the other
      chemicals by season and locations. Net evasion of alpha-HCH from Hudson Bay and
      the Beaufort Sea during open water conditions was shown by air concentrations
      that averaged 14% higher at 1 m than 15 m. No significant difference between the
      two heights was found over ice cover. The alpha-HCH in air over the Beaufort Sea
      was racemic in winter (mean enantiomer fraction, EF = 0.504 +/- 0.008) and
      nonracemic in late spring-early summer (mean EF = 0.476 +/- 0.010). This decrease
      in EF was accompanied by a rise in air concentrations due to volatilization of
      nonracemic alpha-HCH from surface water (EF = 0.457 +/- 0.019). Fluxes of
      chemicals during the southern Beaufort Sea open water season (i.e., Leg 9) were
      estimated using the Whitman two-film model, where volatilization fluxes are
      positive and deposition fluxes are negative. The means +/- SD (and ranges) of net
      fluxes (ng m(-2) d(-1)) were as follows: alpha-HCH 6.8 +/- 3.2 (2.7-13), gamma
      HCH 0.76 +/- 0.40 (0.26-1.4), HCB -9.6 +/- 2.7 (-6.1 to -15), DBA 1.2 +/- 0.69
      (0.04-2.0), and TBA 0.46 +/- 1.1 ng m(-2) d(-1) (-1.6 to 2.0).

PMID- 21194219
TI  - Syntheses and dynamics of donor-acceptor [2]catenanes in water.
AB  - A subset of mechanically interlocked molecules, namely, donor-acceptor
      [2]catenanes, have been produced in aqueous solutions in good yields from readily
      available precursors. The catenations are templated by strong hydrophobic and
      [pi...pi] stacking interactions, which serve to assemble the corresponding
      supramolecular precursors, prior to postassembly covalent modification. Dynamic
      (1)H NMR spectroscopic investigations performed on one of these [2]catenanes
      reveal that the pirouetting motion of the butadiyne-triethylene glycol chain
      occurs with a dramatically lower activation enthalpy, yet with a much higher
      negative activation entropy in water, compared to organic solvents. The
      preparations of mechanically interlocked molecules in water constitute the basis
      for the future development of complex functional molecular machinery in aqueous
      environments.

PMID- 21194220
TI  - Do free-living amoebae in treated drinking water systems present an emerging
      health risk?
AB  - There is an expanding body of evidence that free-living amoebae (FLA) increase
      both the numbers and virulence of water-based, human-pathogenic, amoeba-resisting
      microorganisms (ARM). Legionella spp., Mycobacterium spp., and other
      opportunistic human pathogens are known to be both ARM and also the etiologic
      agents of potentially fatal human lung infections. However, comparatively little
      is known about the FLA that may facilitate ARM growth in drinking water. This
      review examines the available literature on FLA in treated drinking water
      systems; in total 26 studies from 18 different countries. FLA were reported to
      breakthrough the water treatment barrier and enter distribution systems, in
      addition to the expected post-treatment system ingress. Once in the distribution
      system there is evidence of FLA colonization and regrowth especially in
      reservoirs and in-premise plumbing storage tanks. At the point of use the average
      FLA detection rate was 45% but highly variable (n = 16, sigma = 31) due to both
      differences in both assay methods and the type of water systems examined. This
      review reveals that FLA are consistently detected in treated drinking water
      systems around the world and present a yet unquantified emerging health risk.
      However, more research is urgently required before accurate risks assessments can
      be undertaken to assess the impacts on human health, in households and
      institutions, due to exposure to FLA facilitated pathogenic ARM.

PMID- 21194221
TI  - Conformational analysis of aqueous BMP-2 using atomistic molecular dynamics
      simulations.
AB  - BMP-2 is an osteoinductive protein, involved in the differentiation and
      proliferation of osteoblasts, with potential application as bioactive agent in
      bone implants and scaffolds. Since the three-dimensional structure of a protein
      usually determines its bioactivity, in order to efficiently design bone implants
      activated with BMP-2 it is essential to identify the factors influencing the
      protein conformation. In the present work, atomistic molecular dynamics
      simulations are employed to investigate the BMP-2 monomer and homodimer in vacuum
      and water. The influence of each environment on the BMP-2 structure is analyzed
      regarding protein structural changes and energy contributions driving the BMP-2
      conformation.

PMID- 21194222
TI  - Cu-Catalyzed carbon-heteroatom coupling reactions under mild conditions promoted
      by resin-bound organic ionic bases.
AB  - Resin-bound organic ionic bases (RBOIBs) were developed in which tetraalkyl
      ammonium or phosphonium cations are covalently attached to solid resins. The
      application tests showed that the performance of the tetraalkyl-ammonium-type
      RBOIBs is slightly better than that of the corresponding Cs salts in Cu-catalyzed
      C-N cross-couplings, while the tetraalkylphosphonium-type RBOIBs are
      significantly better than all the inorganic bases. With these newly developed
      RBOIBs, room-temperature Cu-catalyzed C-N coupling with various nonactivated aryl
      iodides and even aryl bromides can be readily accomplished. Moreover, RBOIBs can
      be easily recycled and reused for a number of times without much drop of
      activity. The good performances of RBOIBs are proposed to arise from the
      relatively weak binding forces between the cationic polymer backbone and basic
      anions, as opposed to the strong metal-anion interactions in the inorganic bases.
      Further applications of RBOIBs in Ni-catalyzed Suzuki-type couplings at room
      temperature, Cu-catalyzed C-N couplings at -30  degrees C, a Pd-catalyzed Heck
      reaction at 60  degrees C, and Cu-catalyzed C-S couplings at room temperature
      demonstrate that RBOIBs are generally applicable bases with improved performance
      for many other types of organic transformations.

PMID- 21194223
TI  - Exciton scattering on symmetric branching centers in conjugated molecules.
AB  - The capability of the exciton scattering approach, an efficient methodology for
      excited states in branched conjugated molecules, is extended to include symmetric
      triple and quadruple joints that connect linear segments on the basis of the
      phenylacetylene backbone. The obtained scattering matrices that characterize
      these vertices are used in application of our approach to several test
      structures, where we find excellent agreement with the transition energies
      computed by the reference quantum chemistry. We introduce topological charges,
      associated with the scattering matrices, which help to formulate useful relations
      between the number of excitations in the exciton band and the number of repeat
      units. The obtained features of the scattering phases are analyzed in terms of
      the observed excited state electronic structure.

PMID- 21194224
TI  - Conformational enantiomerization and estrogen receptor alpha binding of anti
      cancer drug tamoxifen and its derivatives.
AB  - The anticancer drug tamoxifen (TAM) displays two chiral vinyl propeller
      structures, which interconvert so rapidly that the process is undetectable on the
      NMR time scale. In the present work, the enantiomerization processes were
      investigated with molecular modeling techniques. The threshold mechanisms probed
      at the different rings were shown to be identical, i.e., involving a synchronous
      three-ring flip, with a correlated rotation of the rings. In order to reveal the
      pharmacological profiles of the two chiral forms, we performed structural studies
      on the ligand binding domain of estrogen receptor alpha (ERalpha LBD) and
      associated ligands. The enantiomers, with opposite torsional twist, were found to
      be discriminated by ERalpha. For TAM and its main metabolites, the effects of the
      stereoselectivity of ERalpha are overcome by the low energy cost for helical
      inversion between the two torsional enantiomers, estimated to be ~3 kcal/mol.

PMID- 21194225
TI  - Ultraperformance liquid chromatography-tandem mass spectrometry method for
      biomonitoring cooked meat carcinogens and their metabolites in human urine.
AB  - The cooked meat carcinogens 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and their
      principal metabolites produced by cytochrome P450 and/or uridine diphosphate
      glucuronosyl transferases were simultaneously measured at the parts per trillion
      level in urine of omnivores, by ultraperformance liquid chromatography (UPLC)
      with a Michrom Advance CaptiveSpray source and a triple stage quadrupole mass
      spectrometer. Quantitation was performed in the selected reaction monitoring
      mode. The UPLC method is much more rapid and sensitive than our earlier capillary
      HPLC method: the duty cycle of the UPLC method is 19 min compared to 57 min for
      capillary HPLC. The performance of the UPLC assay was evaluated with urine
      samples from three subjects over 4 different days. The intraday and interday
      precisions of the estimates of PhIP, MeIQx, and their metabolites, reported as
      the coefficients of variation, were <=10%. The limit of quantification (LOQ)
      values for PhIP and MeIQx were about 5 pg/mL, whereas the LOQ values of their
      metabolites ranged from 10 to 40 pg/mL. Furthermore, the identities of the
      analytes were corroborated by acquisition of full scan product ion spectra,
      employing between 0.5 and 5 pg of analyte for assay.

PMID- 21194226
TI  - Surface-functionalized CdS clusters with recognition sites near the interface:
      selective luminescence response to lipophilic phenols.
AB  - A series of water-soluble cadmium sulfide clusters bearing an alkyl-chain layer
      between the inorganic core and the outer PEG layer were synthesized by the ligand
      exchange reaction of Cd(10)S(4)(SPh)(12) with thiols functionalized by an N
      (omega-PEGylated alkyl) amide moiety. The photoluminescence titration experiments
      in aqueous media revealed that clusters with a sufficiently hydrophobic inner
      environment exhibit definite emission enhancements upon the addition of bisphenol
      A or 4-nonylphenol. The dramatic effect of the alkyl chain length on the emission
      responses demonstrated that the hydrophobic layer around the inorganic surface
      serves as guest binding sites to facilitate the access of the lipophilic phenols
      near the organic-inorganic interface. A marked preference for the lipophilic
      phenols over related compounds, such as methylated bisphenol A, long-chain n
      alkanol, and nonlipophilic phenols, was observed in the emission responses of the
      "hydrophobic" cluster, suggesting that not only the hydrophobic interaction but
      also the attractive force involving the phenolic OH group contributes to the
      positive responses. The results of control experiments and IR studies indicated
      that the hydrogen bonding interaction between the phenolic OH group and the amide
      group in the surface organic units is responsible for the positive emission
      responses. The present work shows that the precise tuning of the molecular
      recognition environments near the organic-inorganic interface is useful for
      developing guest-specific functions.

PMID- 21194228
TI  - Directed peptide assembly at the lipid-water interface cooperatively enhances
      membrane binding and activity.
AB  - We modified membrane-active peptides with synthetic recognition modules to foster
      peptide assembly at the lipid-water interface. The designed recognition strategy
      has been previously reported: tris-cyanuric acid and tris-melamine have been
      found to bind selectively to each another when membrane-anchored. We designed
      this interaction to occur between two membrane-active peptides, forming a
      heteromeric complex at the lipid-water interface that exhibits superior membrane
      binding and permeation compared to the monomeric peptides, presumably because of
      the higher avidity of the assembled structure. These conjugates do not assemble
      appreciably in solution but assemble at the lipid-water interface, with surface
      binding of the peptide acting cooperatively with molecular recognition to yield
      improved binding and permeation. Furthermore, we find that specific recognition
      between tris-cyanuric acid phospholipid (TCA-PE) at low surface concentration and
      tris-melamine magainin (TMM) or hexa-melamine magainin (HMM) results in highly
      lytic binding, whereas no binding is detectable in the absence of lipid
      recognition. These findings suggest a noncovalent strategy to enhance peptide
      membrane activity, which may lead to the discovery of more potent surface-active
      agents such as antimicrobials.

PMID- 21194229
TI  - Luminescent ruthenium tripod complexes: properties in solution and on conductive
      surfaces.
AB  - Two luminescent ruthenium complexes containing tripod-type end groups linked
      through a rigid spacer to a phenanthroline derivative, able to confer an axial
      geometry to the complexes, are described. One of the compounds is functionalized
      with thioacetate groups in order to link the metal complex to metallic surfaces.
      The photophysical and electrochemical behavior of the complexes are studied in
      solution and on conductive substrates and, furthermore, self-assembled monolayers
      are investigated in a junction using gold and an indium gallium eutectic, as
      electrodes, and by time-resolved confocal microscopy. The results show that the
      complexes form very stable and well-ordered monolayers because of the tripod
      system, which can anchor the complex almost perpendicular to the surfaces.

PMID- 21194227
TI  - Design and synthesis of potent HIV-1 protease inhibitors incorporating
      hexahydrofuropyranol-derived high affinity P(2) ligands: structure-activity
      studies and biological evaluation.
AB  - The design, synthesis, and evaluation of a new series of hexahydrofuropyranol
      derived HIV-1 protease inhibitors are described. We have designed a
      stereochemically defined hexahydrofuropyranol-derived urethane as the P2-ligand.
      The current ligand is designed based upon the X-ray structure of 1a-bound HIV-1
      protease. The synthesis of (3aS,4S,7aR)-hexahydro-2H-furo[2,3-b]pyran-4-ol, (-)
      7, was carried out in optically active form. Incorporation of this ligand
      provided inhibitor 35a, which has shown excellent enzyme inhibitory activity and
      antiviral potency. Our structure-activity studies have indicated that the
      stereochemistry and the position of oxygens in the ligand are important to the
      observed potency of the inhibitor. Inhibitor 35a has maintained excellent potency
      against multidrug-resistant HIV-1 variants. An active site model of 35a was
      created based upon the X-ray structure of 1b-bound HIV-1 protease. The model
      offers molecular insights regarding ligand-binding site interactions of the
      hexahydrofuropyranol-derived novel P2-ligand.

PMID- 21194230
TI  - Intramolecular oxidative C-H coupling for medium-ring synthesis.
AB  - An oxidative C-H coupling is described for medium-ring synthesis.

PMID- 21194231
TI  - Peptide separation through a CB[8]-mediated supramolecular trap-and-release
      process.
AB  - We demonstrate a supramolecular peptide separation approach by the selective
      immobilization of peptides bearing an N-terminal tryptophan onto a CB[8]-modified
      gold substrate, followed by electrochemical release. The CB[8]-stabilized
      heteroternary complexes were characterized by (1)H NMR, ESI-MS, UV/vis, and
      fluorescence spectroscopy and cyclic voltammetry. Micropatterned CB[8]-modified
      gold substrates were found to trap only the recognizable N-tryptophan-containing
      peptides from a peptide mixture that could be visualized as green peptide arrays
      under fluorescence microscopy. Subsequently, the bound peptides were released
      from the modified substrates by the controlled single-electron reduction of
      viologen. The fully reversible trap-and-release process was repeated for 13
      cycles, and the cumulative release profile of the dye-peptide conjugate was
      monitored by fluorescence spectroscopy, indicating that no degradation occurred.

PMID- 21194233
TI  - Pyrene-linked triazole-modified homooxacalix[3]arene: a unique C3 symmetry
      ratiometric fluorescent chemosensor for Pb2+.
AB  - A new type of fluorescent chemosensor based on homooxacalix[3]arene was
      synthesized. The fluorescent sensor was highly selective for Pb(2+) in comparison
      with other metal ions tested by enhancement of the monomer emission of pyrene.
      The C(3) symmetric structure of homooxacalix[3]arene has potential application in
      the development of a new ratiometric fluorescent chemosensor for heavy metal
      ions.

PMID- 21194235
TI  - Computational insight into small molecule inhibition of cyclophilins.
AB  - Cyclophilins (Cyp) are a family of cellular enzymes possessing peptidyl-prolyl
      isomerase activity, which catalyze the cis-trans interconversion of proline
      containing peptide bonds. The two most abundant family members, CypA and CypB,
      have been identified as valid drug targets for a wide range of diseases,
      including HCV, HIV, and multiple cancers. However, the development of small
      molecule inhibitors that possess nM potency and high specificity for a particular
      Cyp is difficult given the complete conservation of all active site residues
      between the enzymes. Monte Carlo statistical sampling coupled to free energy
      perturbation theory (MC/FEP) calculations have been carried out to elucidate the
      origin of the experimentally observed nM inhibition of CypA by acylurea-based
      derivatives and the >200-fold in vitro selectivity between CypA and CypB from
      aryl 1-indanylketone-based MUM inhibitors. The computed free-energies of binding
      were in close accord with those derived from experiments. Binding affinity values
      for the inhibitors were determined to be dependent upon the stabilization
      strength of the nonbonded interactions provided toward two catalytic residues:
      Arg55 and Asn102 in CypA and the analogous Arg63 and Asn110 residues in CypB.
      Fine-tuning of the hydrophobic interactions allowed for enhanced potency among
      derivatives. The aryl 1-indanylketones are predicted to differentiate between the
      cyclophilins by using distinct binding motifs that exploit subtle differences in
      the active site arrangements. Ideas for the development of new selective
      compounds with the potential for advancement to low-nanomolar inhibition are
      presented.

PMID- 21194234
TI  - Sulfated glycosaminoglycans accelerate transthyretin amyloidogenesis by
      quaternary structural conversion.
AB  - Glycosaminoglycans (GAGs), which are found in association with all extracellular
      amyloid deposits in humans, are known to accelerate the aggregation of various
      amyloidogenic proteins in vitro. However, the precise molecular mechanism(s) by
      which GAGs accelerate amyloidogenesis remains elusive. Herein, we show that
      sulfated GAGs, especially heparin, accelerate transthyretin (TTR) amyloidogenesis
      by quaternary structural conversion. The clustering of sulfate groups on heparin
      and its polymeric nature are essential features for accelerating TTR
      amyloidogenesis. Heparin does not influence TTR tetramer stability or TTR
      dissociation kinetics, nor does it alter the folded monomer-misfolded monomer
      equilibrium directly. Instead, heparin accelerates the conversion of preformed
      TTR oligomers into larger aggregates. The more rapid disappearance of monomeric
      TTR in the presence of heparin likely reflects the fact that the monomer
      misfolded amyloidogenic monomer-oligomer-TTR fibril equilibria are all linked, a
      hypothesis that is strongly supported by the light scattering data. TTR
      aggregates prepared in the presence of heparin exhibit a higher resistance to
      trypsin and proteinase K proteolysis and a lower exposure of hydrophobic side
      chains comprising hydrophobic clusters, suggesting an active role for heparin in
      amyloidogenesis. Our data suggest that heparin accelerates TTR aggregation by a
      scaffold-based mechanism, in which the sulfate groups comprising GAGs interact
      primarily with TTR oligomers through electrostatic interactions, concentrating
      and orienting the oligomers, facilitating the formation of higher molecular
      weight aggregates. This model raises the possibility that GAGs may play a
      protective role in human amyloid diseases by interacting with proteotoxic
      oligomers and promoting their association into less toxic amyloid fibrils.

PMID- 21194237
TI  - Total synthesis of broussonetine F: the orthoamide Overman rearrangement of an
      allylic diol.
AB  - A first total synthesis of broussonetine F from diethyl L-tartrate was achieved.
      The cornerstone of our synthesis was an orthoamide Overman rearrangement, which
      provided an allylic amino alcohol with complete diastereoselectivity.

PMID- 21194236
TI  - Noninvasive MRI-SERS imaging in living mice using an innately bimodal
      nanomaterial.
AB  - We report a novel nanomaterial (AuMN-DTTC) that can be used as a bimodal contrast
      agent for in vivo magnetic resonance imaging (MRI) and Raman spectroscopy. The
      probe consists of MRI-active superparamagnetic iron oxide nanoparticles, stably
      complexed with gold nanostructures. The gold component serves as a substrate for
      a Raman active dye molecule to generate a surface-enhanced Raman scattering
      (SERS) effect. The synthesized probe produces T2 weighted contrast and can be
      used as a SERS active material both in silico (in aqueous solution) and in vivo.
      A quantitative assessment of T2 relaxation times was obtained using multiecho MRI
      analysis. The T2 relaxation times of AuMN-DTTC and MN (dextran-coated iron oxide
      nanoparticles) were 29.23 + 1.45 and 31.58 + 1.7 ms, respectively. The SERS
      signature of AuMN-DTTC revealed peaks at 508, 629, 782, 844, 1080, 1108, 1135,
      and 1242 cm(-1). Intramuscular administration of the probe resulted in a decrease
      of the T2 relaxation time of muscle from 33.4 + 2.5 to 20.3 + 2.2 ms. SERS peaks
      were observed at 508, 629, 782, 844, 1080, 1108, 1135, and 1242 cm(-1),
      consistent with the in silico results. Our studies illustrate for the first time
      the design and in vivo application of a contrast agent, whose component
      modalities include MRI and SERS. The value of this agent lies in its innately
      bimodal nature and its application in vivo for molecular imaging applications.

PMID- 21194238
TI  - Application of a functional mathematical index for antibacterial and
      anticarcinogenic effects of tea catechins.
AB  - Tea leaves produce secondary metabolites that are involved in the defense of the
      plants against invading pathogens. In the case of green teas, these metabolites
      are polyphenolic compounds called catechins. Previous studies developed a
      mathematical formula called functional mathematical index (FMI) that was used to
      describe the quality of different olive oils and potatoes in terms of
      compositional parameters and antioxidative properties of individual components.
      This study extends the development of the FMI concept to define an "optimum tea"
      based on reported relationships between the content of structurally different
      catechins of a large number of teas and their dual beneficial effects:
      antimicrobial activities against a foodborne pathogen and inhibition of human
      cancer cell lines. The described mathematical approach may be useful for
      predicting relative beneficial effects of new teas based on their catechin
      content.

PMID- 21194240
TI  - Small Molecule Inhibitors of Human DNA Polymerase lambda.
AB  - To discover chemical probes to further under-stand the function of individual DNA
      polymerases, we established a generally applicable high-throughput screening. By
      applying this technique we discovered three novel inhibitor classes of human DNA
      polymerase lambda (DNA Pol lambda), a key enzyme to maintain the genetic
      integrity of the genome. The rhodanines, classified as an excellent drug
      scaffold, were found to be the most potent inhibitors for DNA Pol lambda.
      Importantly, they are up to 10 times less active against the highly similar DNA
      polymerase beta. We investigated basic structure activity relationships.
      Furthermore, the rhodanines showed pharmacological activity in two human cancer
      cell lines. So the here reported small molecules could serve as useful DNA Pol
      lambda probes and might serve as starting point to develop novel therapeutic
      agents.

PMID- 21194239
TI  - Imaging LDL receptor oligomerization during endocytosis using a co
      internalization assay.
AB  - Methods to probe receptor oligomerization are useful to understand the molecular
      mechanisms of receptor signaling. Here we report a fluorescence imaging method to
      determine receptor oligomerization state in living cells during endocytic
      internalization. The wild-type receptor is co-expressed with an internalization
      defective mutant, and the internalization kinetics of each are independently
      monitored. If the receptor internalizes as an oligomer, then the wild-type and
      mutant isoforms will mutually influence each others' trafficking properties,
      causing co-internalization of the mutant or co-retention of the wild-type at the
      cell surface. Using this approach, we found that the low density lipoprotein
      (LDL) receptor internalizes as an oligomer into cells, both in the presence and
      absence of LDL ligand. The internalization kinetics of the wild-type receptor are
      not changed by LDL binding. We also found that the oligomerization domain of the
      LDL receptor is located in its cytoplasmic tail.

PMID- 21194241
TI  - Discovery of cyclotides in the fabaceae plant family provides new insights into
      the cyclization, evolution, and distribution of circular proteins.
AB  - Cyclotides are plant proteins whose defining structural features are a head-to
      tail cyclized backbone and three interlocking disulfide bonds, which in
      combination are known as a cyclic cystine knot. This unique structural motif
      confers cyclotides with exceptional resistance to proteolysis. Their endogenous
      function is thought to be as plant defense agents, associated with their
      insecticidal and larval growth-inhibitory properties. However, in addition, an
      array of pharmaceutically relevant biological activities has been ascribed to
      cyclotides, including anti-HIV, anthelmintic, uterotonic, and antimicrobial
      effects. So far, >150 cyclotides have been elucidated from members of the
      Rubiaceae, Violaceae, and Cucurbitaceae plant families, but their wider
      distribution among other plant families remains unclear. Clitoria ternatea
      (Butterfly pea) is a member of plant family Fabaceae and through its usage in
      traditional medicine to aid childbirth bears similarity to Oldenlandia affinis,
      from which many cyclotides have been isolated. Using a combination of nanospray
      and matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF)
      analyses, we examined seed extracts of C. ternatea and discovered cyclotides in
      the Fabaceae, the third-largest family of flowering plants. We characterized 12
      novel cyclotides, thus expanding knowledge of cyclotide distribution and
      evolution within the plant kingdom. The discovery of cyclotides containing novel
      sequence motifs near the in planta cyclization site has provided new insights
      into cyclotide biosynthesis. In particular, MS analyses of the novel cyclotides
      from C. ternatea suggest that Asn to Asp variants at the cyclization site are
      more common than previously recognized. Moreover, this study provides impetus for
      the examination of other economically and agriculturally significant species
      within Fabaceae, now the largest plant family from which cyclotides have been
      described.

PMID- 21194242
TI  - Effect of n-alkyl and sulfonyl groups on the wetting properties of comblike
      poly(oxyethylene)s and stick-slip behavior.
AB  - The influence of side chain length and sulfonyl moiety on the molecular
      structures and wettability behavior of poly(oxyethylene)s with alkyl sulfonyl
      side chains (CH(3)-nSE, n = 1, 2, 3, 4, 5, 6, 8, 10), where n is the number of
      the carbon atom in the n-alkyl side group, was investigated. CH(3)-nSEs having
      shorter side chains (n < 5) do not have ordered structures, and their surfaces
      were found to be more polar than those of CH(3)-nSEs having longer side chains (n
      >= 5). The CH(3)-nSEs having longer side chains show double-layered lamellar
      structures (n >= 5) with well-aligned side chains and low surface energies in the
      range 21.2-25.8 mN/m. Interestingly, stick-slip behavior was observed only on the
      surfaces of CH(3)-3SE and CH(3)-4SE when water was used as the test liquid. The
      surface deformation at the three-phase line was generated from interactions
      between water and sulfonyl groups, and the optimum side chain lengths were
      believed to cause the stick-slip behavior.

PMID- 21194244
TI  - Planning for children's future - there are more important things than a college
      fund!

PMID- 21194245
TI  - Randomized controlled trial of electro-acupuncture for autism spectrum disorder.

PMID- 21194246
TI  - Case report: heavy metal burden presenting as Bartter syndrome.
AB  - CONTEXT: Maternal transfer of heavy metals during fetal development or lactation
      possibly contributed to the clinical manifestations of Bartter syndrome and
      developmental delay in the offspring. CASE PRESENTATION: An 11-month-old child
      diagnosed with Bartter syndrome and failure to thrive was treated concurrently
      for elevated metal burden while he was undergoing standard medical interventions.
      Treatment with body-weight doses of meso-2,3-dimercaptosuccinic acid (DMSA)
      reduced the body burden of lead, beryllium, copper, mercury, and cadmium at the
      three- and sixth-month follow-up tests. During the course of the six-month
      treatment, the patient gained 2.4 kg (5.2 lb) and grew approximately 9.5 cm (3.75
      in). His weight shifted from significantly below the 5th percentile in weight to
      within the 5th percentile, and from below the 5th to within the 10th percentile
      for length. DISCUSSION: The child's acquisition of lead, beryllium, and copper
      correspond to his mother's history of stained glass assembly and occurred during
      fetal development or lactation, since there were no other identifiable sources
      that could have contributed to the heavy metal burden. Tests for known genetic
      mutations leading to Bartter syndrome were all negative. RELEVANCE TO CLINICAL
      PRACTICE: This case report highlights the potential benefit of DMSA for treatment
      of heavy metal body burden in infants who present with Bartter syndrome.

PMID- 21194247
TI  - A review of the sirtuin system, its clinical implications, and the potential role
      of dietary activators like resveratrol: part 2.
AB  - The silent information regulator (SIR) genes (sirtuins) comprise a highly
      conserved family of proteins, with one or more sirtuins present in virtually all
      species from bacteria to mammals. In mammals seven sirtuin genes - SIRT1 to SIRT7
      - have been identified. Emerging from research on the sirtuins is a growing
      appreciation that they are a very complicated biological response system that
      influences many other regulator molecules and pathways in complex manners. Part 1
      of this article provided an overview of the mammalian sirtuin system, discussed
      the dietary, lifestyle, and environmental factors that influence sirtuin
      activity, and summarized research on the importance of vitamin B3 in supporting
      sirtuin enzyme activity, as well as the role specifically of the amide form of
      this vitamin - nicotinamide - to inhibit sirtuin enzyme activity. In Part 2 of
      this review, clinical situations where sirtuins might play a significant role,
      including longevity, obesity, fatty liver disease, cardiovascular health,
      neurological disease, and cancer are discussed. Research on the ability of
      nutritional substances, especially resveratrol, to influence sirtuin expression
      and function, and hence alter the courses of some clinical situations, is also
      reviewed.

PMID- 21194248
TI  - Evaluation of hemostatic effects of Ankaferd as an alternative medicine.
AB  - Ankaferd Blood Stopper (ABS), a unique traditional herbal mixture, has been used
      topically to stop bleeding for centuries in Anatolia. ABS is a standardized
      mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera,
      Alpinia officinarum, and Urtica dioica. Through its effects on the endothelium,
      blood cells, angiogenesis, cellular proliferation, vascular dynamics, and cell
      mediators, ABS is now becoming an official alternative hemostatic medicine for
      intractable bleedings that are resistant to conventional anti-hemorrhagic
      measurements in Turkey. Furthermore, ABS seems to have a considerable therapeutic
      benefit, because of its anti-infective, anti-neoplastic, and wound healing
      properties, to restore and maintain tissue homeostasis in a variety of diseases.

PMID- 21194249
TI  - Efficacy and safety of Meriva(r), a curcumin-phosphatidylcholine complex, during
      extended administration in osteoarthritis patients.
AB  - In a previous three-month study of Meriva, a proprietary curcumin
      phosphatidylcholine phytosome complex, decreased joint pain and improvement in
      joint function were observed in 50 osteoarthritis (OA) patients. Since OA is a
      chronic condition requiring prolonged treatment, the long-term efficacy and
      safety of Meriva were investigated in a longer (eight months) study involving 100
      OA patients. The clinical end points (Western Ontario and McMaster Universities
      [WOMAC] score, Karnofsky Performance Scale Index, and treadmill walking
      performance) were complemented by the evaluation of a series of inflammatory
      markers (interleukin [IL]-1beta, IL-6, soluble CD40 ligand [sCD40L], soluble
      vascular cell adhesion molecule (sVCAM)-1, and erythrocyte sedimentation rate
      [ESR]). This represents the most ambitious attempt, to date, to evaluate the
      clinical efficacy and safety of curcumin as an anti-inflammatory agent.
      Significant improvements of both the clinical and biochemical end points were
      observed for Meriva compared to the control group. This, coupled with an
      excellent tolerability, suggests that Meriva is worth considering for the long
      term complementary management of osteoarthritis.

PMID- 21194250
TI  - The vitamin C:vitamin K3 system - enhancers and inhibitors of the anticancer
      effect.
AB  - The oxidizing anticancer system of vitamin C and vitamin K3 (VC:VK3, producing
      hydrogen peroxide via superoxide) was combined individually with melatonin,
      curcumin, quercetin, or cholecalciferol (VD3) to determine interactions.
      Substrates were LNCaP and PC-3 prostate cancer cell lines. Three of the tested
      antioxidants displayed differences in cell line cytotoxicity. Melatonin combined
      with VC:VK3 quenched the oxidizing effect, while VC:VK3 applied 24 hours after
      melatonin showed no quenching. With increasing curcumin concentrations, an
      apparent combined effect of VC:VK3 and curcumin occurred in LNCaP cells, but not
      PC-3 cells. Quercetin alone was cytotoxic on both cell lines, but demonstrated an
      additional 50-percent cytotoxicity on PC-3 cells when combined with VC:VK3. VD3
      was effective against both cell lines, with more effect on PC-3. This effect was
      negated on LNCaP cells with the addition of VC:VK3. In conclusion, a natural
      antioxidant can enhance or decrease the cytotoxicity of an oxidizing anticancer
      system in vitro, but generalizations about antioxidants cannot be made.

PMID- 21194251
TI  - Sulforophane glucosinolate. Monograph.

PMID- 21194252
TI  - Bromelain. Monograph.

PMID- 21194254
TI  - First report on the co-inheritance of beta-globin IVS-I-5 (G-->C) thalassemia
      with delta globin CD12 {Asn-->Lys (AAT-->AAA)}HbA2-NYU in Iran.
AB  - BACKGROUND: Co-inheritance of beta- and delta-globin mutations in Iran is not
      uncommon. This situation may interfere with correct diagnosis and genetic
      counseling of alpha- and beta-thalassemia in screening programs. Here we report
      the co-inheritance of beta- and delta-globin gene mutations in an individual with
      microcytosis, hypochromia and a normal hemoglobin A2 (HbA2) level. METHODS:
      Genomic DNA extraction, amplification refractory mutation system (ARMS)
      polymerase chain reaction and direct DNA sequencing of delta- and beta-globin
      genes were exploited for detection of the mutations in these two genes in an
      individual with low hematological indices and normal HbA2. RESULTS: ARMS-PCR
      technique revealed the beta(+) IVSI-5 (G to C) mutation and direct DNA sequencing
      of the delta-globin gene detected a previously reported delta codon 12 (AAT-
      >AAA) HbA2-NYU. This study reports HbA2-NYU in association with the beta IVSI-5
      (G to C) mutation in Iran. DISCUSSION: This report emphasizes that normal HbA2
      expression in a beta-goblin carrier is due to mutation in the delta-globin gene
      and may cause misdiagnosis of thalassemia.

PMID- 21194255
TI  - Autologous transplantation of bone marrow-derived mononuclear and CD133(+) cells
      in patients with decompensated cirrhosis.
AB  - BACKGROUND: Cirrhosis, the end stage of progressive hepatic fibrosis, is
      characterized by distortion of the hepatic architecture and the formation of
      regenerative nodules. Liver transplantation is one of the few available therapies
      for such patients. However, due to a severe shortage of organ donors, surgical
      complications, transplant rejection and the high cost of this procedure much
      interest has focused on research to find new treatment modalities for this
      disease. There is accumulating evidence for the contribution of bone marrow stem
      cells to participate in liver regeneration. METHODS: Here we report on six
      patients with end stage liver disease who were subjected to intraportal
      administration of autologous bone marrow-derived CD133(+) in comparison to
      mononuclear cells in short-term (6 months) and long-term (24 months) follow up.
      RESULTS: There were no adverse effects in any of the patients during the short-
      and long-term follow up period. Moreover, there were no significant alterations
      of liver function parameters, liver enzymes, serum albumin, creatinine, serum
      bilirubin and/or liver volume after transplantation of both types of autologous
      cells in these patients. CONCLUSION: Our study has shown both the safety and
      feasibility of this type of liver cell therapy and may be a bridge to liver
      transplantation. The trial was registered with NIH clinical trials
      (www.clinicaltrials.gov) as identifier: NCT00713934.

PMID- 21194256
TI  - Evaluation of Fast-ELISA versus standard-ELISA to diagnose human fasciolosis.
AB  - BACKGROUND: The present study was conducted to evaluate and compare a fast-ELISA
      (F-ELISA) method versus standard-ELISA (S-ELISA) to diagnose human fasciolosis.
      METHODS: Serum samples were obtained from 35 individuals infected with
      fasciolosis, 27 infected with other parasitoses and 22 from healthy people. The
      samples were examined with S-ELISA (30-minute incubation periods) and F-ELISA (10
      minute incubation periods) for total antibody response against fasciolosis.
      RESULTS: The optimum conditions for S-ELISA and F-ELISA were respectively as
      follows: antigen 10 and 5 ug/mL, sera 1:500 dilution for both, peroxidase
      conjugated goat anti-human IgG diluted 1:7000 and 1:10000. Data were analyzed
      using SPSS version 11.0. Cut-off vale for S-ELISA and F-ELISA was determined as
      0.56 and 0.42, respectively. The sensitivity, specificity; positive, and negative
      predictive values were detected as 97.2%, 100%, 94.6%, and 95.6% for both tests.
      CONCLUSION: Cut-off values, sensitivity, specificity, and other important
      parameters of the two evaluated tests determined that the F-ELISA method could be
      used with no detectable difference.

PMID- 21194257
TI  - Assessments of pulmonary involvement in patients with systemic sclerosis.
AB  - BACKGROUND: The lungs are affected in 70 - 90% of cases diagnosed with systemic
      sclerosis. Pulmonary involvement is associated with increased morbidity and
      mortality. MATERIALS AND METHODS: Fifty-five cases of systemic sclerosis
      underwent plethysmography, diffusion lung capacity for carbon monoxide (DLCO)
      measurement, high resolution computed tomography scanning, and bronchoalveolar
      lavage (BAL) to evaluate their diagnostic roles in grading the severity of lung
      involvement and their relationships to each other. RESULTS: The indices of DLCO%
      (measured DLCO to predicted ratio) and DLCO value, total lung capacity (TLC)
      value and TLC% (measured TLC to predicted ratio), forced vital capacity (FVC) and
      FVC% (measured FVC to predicted FVC) were significantly lower in patients who
      presented with a severer degree of lung involvement on high resolution computed
      tomography scan. No meaningful correlation between bronchoalveolar lavage
      findings and the degree of involvement on high resolution computed tomography
      scan was noted. CONCLUSION: Although there is a correlation between imaging and
      lung capacities in physiologic studies. Bronchoalveolar lavage findings did not
      correlate with either imaging or physiologic tests. It seems that DLCO, TLC, and
      FVC are the most valuable measures with which to evaluate disease severity.

PMID- 21194258
TI  - Comparison of anthropometric and biochemical indices of adolescents born during
      and after the Iran-Iraq war; Tehran Lipid and Glucose Study.
AB  - BACKGROUND: A country's developmental progress and overall changes in socio
      economic structure are reflected in the outcome of secular trend studies on
      physical growth of children. The aim of this study was to compare anthropometric
      and biochemical indices of adolescent boys and girls born during and after the
      Iran-Iraq war. METHODS: Adolescents, aged 11 - 18 years, were selected from the
      TLGS cohort and divided into two groups. In the first group, adolescents born
      during the war and in the second group adolescents born after the war were
      included. Height, weight, serum lipids, FBS, systolic and diastolic blood
      pressure, and BMI were compared amongst adolescents of the same ages between the
      two groups. RESULTS: Mean weight and height increased at the ages of 12, 13, 14,
      and 17 years in boys of the post-war group. The mean weight of girls in the post
      war group increased at the ages of 11, 13, and 14 years. Between 11 - 14 years,
      the means for total and LDL cholesterol, and between the ages of 15 - 18 years
      FBS, total cholesterol and LDL cholesterol decreased in boys of the post-war
      group. For girls between the ages of 11 - 14, FBS, total cholesterol, TG and LDL
      cholesterol, and between the ages of 15 - 18 years, FBS, total cholesterol and
      LDL cholesterol decreased in the post-war group. Systolic and diastolic blood
      pressure decreased at all ages in both groups. CONCLUSION: This study showed that
      some anthropometric indices such as height and weight increased in boys who were
      born after the war; but in girls, the mean weight in the age groups increased.
      Systolic and diastolic blood pressure, and some lipid profiles decreased in boys
      and girls of the post-war group.

PMID- 21194259
TI  - Repeated pretreatment of morphine prevents morphine-induced amnesia: A possible
      involvement for dorsal hippocampal NMDA receptors.
AB  - BACKGROUND: Learning and memory processes can be affected by morphine
      administration. It has been previously demonstrated that the effects of morphine
      depend on the timing of drug administration. In the present study, the effects of
      microinjections of a NMDA receptor agonist and antagonist into the CA1 regions of
      the dorsal hippocampi (intra-CA1) on repeated pretreatment of morphine-induced
      prevention of morphine-induced amnesia have been investigated. METHODS: Step
      through inhibitory avoidance task of memory has been used to examine retrieval of
      memory formation, 24 h after training in male Wistar rats. RESULTS: The results
      indicate that post-training administration of morphine (7.5 mg/kg) impaired
      memory retrieval, but not in the animals, which received previous repeated
      morphine (7.5 and 10 mg/kg) injections followed by morphine withdrawal. Repeated
      co-administration of NMDA (7.5 and 10 ng/rat, intra-CA1) with an ineffective dose
      of morphine (5 mg/kg), once daily for three days reversed morphine-induced
      amnesia. Repeated bilateral intra-CA1 microinjections of NMDA, once daily for
      three days followed by a five-day washout had no effect on the expression of
      amnesia produced by post-training morphine. Three-day administration of the NMDA
      receptor antagonist, D-AP5 (0.5 - 2 ug/rat, intra-CA1) followed by a five-day
      washout had no effect on morphine-induced amnesia. On the other hand, intra-CA1
      microinjections of the same doses of D-AP5 prior to injection of 7.5 mg/kg of
      morphine (per day*3 days) decreased the reversal of morphine-induced amnesia.
      CONCLUSION: These data imply that the dorsal hippocampal NMDA receptor
      mechanism(s) may modulate the effect-induced by repeated morphine administration
      on a challenge dose of morphine-induced amnesia.

PMID- 21194260
TI  - Human rotavirus genotypes detection among hospitalized children, a study in
      Tehran, Iran.
AB  - BACKGROUND: Human rotavirus genotypes G1-G4, G9, P[4] and P[8] are major
      worldwide causes of acute gastroenteritis in children. Rotavirus genotype G1P[8]
      is predominant in many countries. In this study, the genotypic diversity of group
      A rotaviruses were detected in children <5 years of age who were treated for
      dehydration and diarrhea in Tehran, Iran from October 2004 to September 2008.
      METHODS: A total of 700 stool specimens were collected from children and assessed
      for the presence of rotaviruses by the dsRNA-PAGE technique. G and P typing of
      the positive samples were performed by semi-nested multiplex RT-PCR. RESULTS:
      Rotaviruses were isolated in 19% of samples. A total of 14 rotavirus dsRNA
      different electrophoretypes were detected. The predominant genotype was G1
      (76.3%), followed by G4 (11.5%), G8 (0.8%), P[4] (9.2%) and P[8] (66.4%),
      respectively. In mixed type samples, the majority were of genotype G1P[8]
      (53.4%), followed by G1P[4] (9.2%) and G4P[8] (4.6%). Mixed types consisted of
      3.1% of the total sample followed by G1G2/-P (1.5%), G1G4P[4] (0.8%) and G1G4P[8]
      (0.8%). CONCLUSION: In this study, a high prevalence of the G1P[8] genotype was
      determined to be the cause of childhood gastroenteritis in Tehran, Iran. The
      sequence of G and P genotypes showed high levels of similarity to strains from
      other Asian countries. Our data will be useful for future vaccine formulation in
      Iran.

PMID- 21194261
TI  - Effectiveness and feasibility of lifestyle and low-cost pharmacologic
      interventions in the prevention of chronic diseases: a review.
AB  - Chronic diseases are already major causes of morbidity and mortality in Iran,
      similar to what is seen in other countries. However, there doesn't yet exist a
      comprehensive plan to cope with the epidemic of chronic diseases in Iran. Several
      lifestyle and low-cost pharmacological interventions have been proposed to reduce
      the burden of chronic diseases. Lifestyle interventions require a comprehensive
      infrastructure that can be quite costly in this country, but several components
      of extensive lifestyle interventions, including self-help materials and brief
      advice by health workers, can be integrated into the existing system.
      Pharmacological interventions may have substantial contribution to the capacity
      and preparation of Iran's healthcare system to confront the epidemic of chronic
      diseases. Further research needs to be performed to determine the feasibility and
      efficacy of each of these methods in order for policy makers to take the
      appropriate measures on adopting each of these strategies to prevent and control
      chronic diseases.

PMID- 21194263
TI  - Application of peer review in investigating allegations of medical negligence and
      malpractice.

PMID- 21194262
TI  - Euthanasia, terminal illness and quality of life.

PMID- 21194264
TI  - Educational level and pseudohypacusis in medico-legal compensation claims: a
      retrospective study.
AB  - Pseudohypacusis or the intentional feigning of hearing loss is a challenging
      situation in the medicolegal evaluation of hearing levels. Few studies have been
      performed on predisposing factors that make compensation claims susceptible to
      malingering. The goal of this study was to investigate the relationship between
      educational level and frequency of pseudohypacusis in a group of medico-legal
      clients. Retrospectively, we studied the files of subjects (n=421) referred to
      the audiology clinic of a government hospital during a 12 month period.
      Educational levels of the individuals with and without pseudohypacusis were
      compared by the Chi-square test. The results show that individuals with
      pseudohypacusis have lower educational levels than cooperative clients. The
      relative frequency of individuals with pseudohypacusis among illiterates (43.5%)
      was clearly higher than individuals with higher educational levels (17.5%). The
      education level of a person filing a compensation claim may alert an examiner in
      detecting pseudohypacusis.

PMID- 21194265
TI  - Co-inheritance of hemoglobin D and beta-thalassemia traits in three Iranian
      families: clinical relevance.
AB  - Here we report the result of three cases referred to our lab that had a
      combination of beta-thalassemia and hemoglobin D (Hb D) traits. These individuals
      had no symptoms of profound anemia and hematological indices were similar to that
      of a beta-thalassemia heterozygote. In all three cases, the Hb D level was
      elevated and no HbA was detected electrophoretically. The electrophoresis pattern
      suggested that all cases were homozygotes for Hb D. PCR followed by digestion
      with EcoRI and sequencing of the beta-globin gene confirmed the presence of Cd
      121 GAA>CAA in the heterozygous form with another beta-globin mutation. In all
      cases, the mutations in the beta-globin gene were detected by ARMS PCR technique
      and they were either IVSII-I or IVSI-5. Hematological studies of the family
      members showed that thalassemia which caused the mutations and Hb D were in the
      trans position.

PMID- 21194266
TI  - Facial metastasis from colon cancer.
AB  - Facial metastasis from colorectal cancer is very unusual. Herein, we report a 53
      year-old man with history of colon cancer who was referred to our clinic because
      of an asymptomatic nodule on his chin for one year. Histopathologic examination
      of the nodule revealed metastatic adenocarcinoma, which was similar to that of
      the primary colon adenocarcinoma. The patient underwent radiotherapy for his skin
      metastasis, but he died 13 months later from widespread metastasis. I have no
      conflict of interest and no source of support.

PMID- 21194267
TI  - Successful treatment of recurrent pancreatitis secondary to systemic lupus
      erythematosus with B-cell depletion therapy.
AB  - Recurrent pancreatitis secondary to systemic lupus erythematosus is a rare entity
      of unknown etiology. We report an adolescent with systemic lupus erythematosus
      and recurrent attacks of acute pancreatitis, which were poorly controlled with
      conventional therapy for approximately four years. Rituximab, a chimeric anti
      CD20 monoclonal antibody therapy resulted in remission of symptoms for more than
      two years without major toxicity of treatment. Based on tolerability and high
      efficiency of rituximab therapy, we would suggest using B-cell depletion therapy
      as an alternative therapy for refractory pancreatitis secondary to systemic lupus
      erythematosus.

PMID- 21194268
TI  - Photoclinic. Fixed drug eruption.

PMID- 21194269
TI  - Razi's description and treatment of facial paralysis.
AB  - In the modern medical era, facial paralysis is linked with the name of Charles
      Bell. This disease, which is usually unilateral and is a peripheral facial palsy,
      causes facial muscle weakness in the affected side. Bell gave a complete
      description of the disease; but historically other physicians had described it
      several hundred years prior although it had been ignored for different reasons,
      such as the difficulty of the original text language. The first and the most
      famous of these physicians who described this disease was Mohammad Ibn Zakaryya
      Razi (Rhazes). In this article, we discuss his opinion.

PMID- 21194270
TI  - A pilot double-blind randomised placebo-controlled trial of the effects of fixed
      dose combination therapy ('polypill') on cardiovascular risk factors.

PMID- 21194272
TI  - Sex differences in the relationship between leukocyte count and chronic kidney
      disease: the 2007 Korean National Health and Nutrition Examination Survey.
AB  - BACKGROUND: Chronic kidney disease (CKD) has emerged as an independent predictor
      for cardiovascular disease (CVD), which is now regarded as an inflammatory
      disease. This study aimed to determine the association of CKD with white blood
      cell (WBC) count as a marker of systemic inflammation. METHODS: We examined the
      association of WBC count with CKD in 2825 Korean adults (1155 men, 1670 women) in
      the 2007 Korean National Health and Nutrition Examination Survey (KNHANES). CKD
      was defined as either proteinuria or a glomerular filtration rate (GFR) <60
      mL/min/1.73 m(2). The odds ratios (ORs) for CKD were calculated using
      multivariate logistic regression analysis after adjusting for confounding
      variables across gender-specific WBC count quartiles. RESULTS: The proportion of
      CKD increased with increasing WBC quartiles, from 9.7% in the lowest quartile to
      20.7% in the highest quartile for women. In multivariate logistic regression
      analysis, the corresponding odds ratios (95% confidence intervals [CIs]) for a
      CKD across WBC count quartiles among women were 1.00, 1.45 (0.91-2.31), 1.65
      (1.03-2.63), and 2.11 (1.33-3.35), after adjusting for age, body mass index
      (BMI), systolic blood pressure, fasting plasma glucose, smoking status, current
      drinking high-density lipoprotein cholesterol (HDL-C), and triglyceride. In
      contrast, compared with women, men appeared to have no significant results of a
      relationship between WBC quartiles and CKD. CONCLUSIONS: Our study shows a
      significant association between WBC count and the risk for CKD in women.
      Accordingly, potential health benefits of early detection of a higher level of
      WBC count may be useful for CKD risk assessment in women.

PMID- 21194273
TI  - Prepregnancy body mass index as an independent risk factor for pregnancy-induced
      hypertension.
AB  - BACKGROUND: Pregnancy-induced hypertension (PIH) plays a major role in the
      perinatal outcome for mother and neonate. With the rising prevalence of obesity,
      the role of prepregnancy body mass index (BMI) as an independent risk factor for
      PIH and a target for preconception care is important to explore. METHODS: We
      completed a retrospective cohort study of 16,582 women who received obstetrical
      care at a regional medical center and delivered a singleton pregnancy between
      2003 and 2006. Clinical data were derived from the electronic medical record.
      Logistic regression was used to explore the association of demographic
      characteristics and medical risk factors with the outcome of PIH. RESULTS:
      Diagnoses of chronic hypertension, prepregnancy diabetes, and gestational
      diabetes were more likely in women with increasing prepregnancy maternal BMI (p <
      0.0001). The odds of PIH also increased with BMI, ranging from an odds ratio (OR)
      of 1.99 (95% confidence interval [CI] 1.73-2.31) for overweight women through OR
      4.26 (95% CI 3.37-5.38) for those with a BMI of >=40 kg/m(2). Other risk factors
      for PIH included chronic hypertension (OR 6.57, 95% CI 5.43-7.95), nulliparity
      (OR 1.89, 95% CI 1.69-2.12), prepregnancy diabetes (OR 2.05, 95% CI 1.33-3.17),
      and gestational diabetes (OR 1.28, 95% CI 1.04-1.58). The presence of chronic
      hypertension modified the association between obesity and PIH; for women with
      chronic hypertension, obesity was not associated with PIH (adjusted OR [aOR]
      1.39, 95% CI 0.77-2.50 for BMI 30-34.9; aOR 0.98, 95% CI 0.52-1.87 for BMI 35
      39.9; and aOR 1.33, 95% CI 0.73-2.43 for BMI >=40 kg/m(2)) compared with women
      with a BMI in the normal range. CONCLUSIONS: The risk of PIH rises with maternal
      prepregnancy BMI independent of other obesity-associated comorbidity. Women with
      chronic hypertension carry the greatest risk of PIH but incur no obesity
      associated increase in risk.

PMID- 21194274
TI  - Primitive neuroectodermal tumors of the spine: a comprehensive review with
      illustrative clinical cases.
AB  - Primary spinal primitive neuroectodermal tumors (PNETs) are uncommon malignancies
      that are increasingly reported in the literature. Spinal PNETs, like their
      cranial counterparts, are aggressive tumors and patients with these tumors
      typically have short survival times despite maximal surgery, chemotherapy, and
      radiation. Because no standard management guidelines exist for treating these
      tumors, a multitude of therapeutic strategies have been employed with varying
      success. In this study the authors perform a comprehensive review of the
      literature on primary spinal PNETs and provide 2 new cases that highlight the
      salient features of their clinical management.

PMID- 21194275
TI  - Embryonal tumors with abundant neuropil and true rosettes: 2 illustrative cases
      and a review of the literature.
AB  - Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is a recently
      identified variant of primitive neuroectodermal tumor, with fewer than 50 cases
      reported in the literature to date. Histologically, this tumor has features of
      ependymoblastoma and neuroblastoma, demonstrating areas of fine fibrillary
      neuropil intermingled with ependymoblastic rosettes and zones of undifferentiated
      neuroepithelial cells. However, ETANTR is distinguished pathologically from other
      embryonal tumors by the striking abundance of neuropil. Clinically, ETANTRs have
      shown high malignant potential and poor clinical outcome despite aggressive
      treatment. The authors describe 2 illustrative surgical cases of ETANTR, one
      involving the longest reported survival in the literature to date. The other had
      a poor outcome despite high-dose adjuvant chemotherapy with sequential autologous
      hematopoietic stem cell rescue. The authors review the natural history and
      treatment strategies available for this unusual malignant pediatric brain tumor.

PMID- 21194276
TI  - Primitive neuroectodermal tumor after radiation therapy for craniopharyngioma.
AB  - The authors report a case of primitive neuroectodermal tumor induced by radiation
      therapy of craniopharyngioma. This African-American male patient originally
      presented with craniopharyngioma, for which he underwent resection and whole
      brain radiation therapy. Eight years later, at the age of 20 years, he returned
      with a left facial droop and left hemiparesis. A right basal ganglia mass was
      identified and resected. Histopathological examination identified the lesion as
      primitive neuroectodermal tumor. Although radiation therapy has shown to be
      beneficial in decreasing the recurrence rate in subtotally resected
      craniopharyngioma, the risks of radiation treatment should be clearly
      communicated to the patients, their families, and neurosurgeons before starting
      such treatment. This report expands the spectrum of reported radiation-induced
      neoplasms in the CNS.

PMID- 21194277
TI  - Central nervous system primitive neuroectodermal tumors: still a useful
      classification?

PMID- 21194278
TI  - Editorial. Vein of Galen malformation.

PMID- 21194279
TI  - Endovascular treatment of vein of Galen aneurysmal malformation: management
      strategy and 21-year experience in Toronto.
AB  - OBJECT: The treatment of vein of Galen aneurysmal malformation (VGAM) is among
      the most challenging of all the neurovascular disorders. METHODS: Between 1984
      and 2005, 26 consecutive patients with VGAMs were treated by the authors' group,
      and their data were prospectively collected; 12 patients presented with
      congestive heart failure (CHF) and 10 had hydrocephalus. Five patients did not
      undergo endovascular treatment because of minimal symptoms or severe
      comorbidities. Twelve patients underwent embolization for refractory CHF
      requiring ventilation: 7 of these 12 patients had the procedure in the neonatal
      stage (5 survived), and 5 were treated in infancy or childhood following
      successful aggressive medical treatment (4 survived). The other 9 patients
      underwent endovascular surgery to treat a progressively enlarging head
      circumference; there was imaging evidence of ventricular enlargement and/or signs
      of developmental delay (6 underwent surgery in infancy and 3 in childhood; 1
      patient died). RESULTS: The survival rate in this series was 76.9% (20 of 26).
      Fourteen (66.7%) of 21 patients who underwent endovascular treatment had no
      developmental delay. An analysis of various factors demonstrated that
      comorbidities and embolization effect (procedure success and long-term effect)
      were prognostic factors of survival. In addition, the patient's age at
      embolization was significantly higher in those with developmental delay than in
      those without (559.86 +/- 535.43 days vs 94.83 +/- 95.77 days, respectively; p =
      0.028). CONCLUSIONS: The authors conclude that neonatal VGAMs can be treated
      successfully with a strategic approach integrating antenatal diagnosis,
      endovascular surgery, treatment at intensive care facilities, and the cooperative
      efforts of different specialties. In the authors' experience, patients in whom
      VGAM was diagnosed and managed in infancy or childhood had more than 90% long
      term survival.

PMID- 21194280
TI  - Surgical treatment and perioperative management of moyamoya disease associated
      with glycogen storage disease Type 1a.
AB  - The authors report a case of concurrent moyamoya disease and glycogen storage
      disease Type 1a that was successfully managed with bypass surgery. This 7-year
      old Japanese girl, diagnosed with glycogen storage disease Type 1a at the age of
      2 years, presented with repeated transient ischemic attacks. Cerebral angiography
      revealed severe stenosis at the terminal portions of the bilateral internal
      carotid arteries, with typical moyamoya vessels. The patient underwent
      superficial temporal artery-middle cerebral artery anastomosis and
      encephalomyosynangiosis bilaterally, in 2 staged procedures at an interval of 4
      months. Despite perioperative administration of glucose, hypoglycemia and
      metabolic acidosis occurred after both surgeries. The symptoms were milder after
      the second surgery, in which an increased dose of glucose was used. The patient
      tolerated the perioperative conditions well under intensified medical treatment,
      and no further ischemic symptoms occurred.

PMID- 21194281
TI  - Large vascular malformation in a child presenting with vascular steal phenomenon
      managed with pial synangiosis.
AB  - The management of large and giant arteriovenous malformations (AVMs) in patients
      presenting with nonhemorrhagic neurological deficits secondary to vascular steal
      phenomenon is challenging and controversial. In many cases, large AVMs cannot be
      completely excised or cured, leaving patients with residual or partially treated
      AVMs, the natural history of which is unknown. Additionally, large, diffuse
      vascular malformations with multiple, small feeders, slow flow, or so-called
      cerebral proliferative angiopathy represent a related but distinct clinical and
      angiographic entity that may require a different therapeutic approach than
      traditional brain AVMs. The current management of children with other conditions
      of chronic cerebral hypoperfusion, such as moyamoya disease, involves
      consideration of surgical revascularization to enhance blood flow to the
      compromised hemisphere. Here, the authors present the case of a young child with
      a large thalamic vascular malformation who presented with clinical and
      radiological features of vascular steal and ischemia. In an effort to augment
      flow to the hypoperfused brain and protect against future ischemia, the authors
      treated the child with unilateral pial synangiosis. At 12 months, postoperative
      angiography demonstrated robust neovascularization, and the child has not
      sustained any further ischemic events. The authors discuss concept of vascular
      malformation-related hypoperfusion and the utility of indirect revascularization
      for inoperable vascular malformations presenting with ischemic symptoms.

PMID- 21194282
TI  - Editorial. Chiari malformation Type I and scoliosis: the complexity of curves.

PMID- 21194283
TI  - Scoliosis and Chiari malformation Type I in children.
AB  - OBJECT: The identification of Chiari malformations Type I (CM-Is) has increased
      in recent years, commonly during MR imaging for evaluation of a possible cause of
      scoliosis. The treatment of this abnormality remains controversial, and the
      expected success of treatment is unclear. The goal of the present study is to
      evaluate the effects of a craniotomy for CM-I decompression on scoliosis in
      children and adolescents. METHODS: The authors conducted a 10-year retrospective
      review of pediatric patients who were found to have a CM-I during evaluation for
      scoliosis. Seventy-nine patients were identified, ranging in age from 6 months to
      18 years (median 12 years). There were 42 girls (54%) and 37 boys (46%). All were
      noted on MR imaging to have hydrosyringomyelia of the spinal cord. Forty-nine
      patients had curvatures less than 20 degrees  prior to treatment. The other 30
      patients had curves ranging from 25 degrees  to 80 degrees  and underwent
      orthopedic follow-up and treatment. None of these patients were referred for
      specific neurological complaints, but 12 (16%) had neurological signs on physical
      examination. All were treated with a craniocervical decompression in a standard
      fashion. Follow-up ranged from 6 to 93 months with a median of 35 months.
      Magnetic resonance images obtained at 6 months postoperatively and serial
      standing anteroposterior spine radiographs were used to evaluate outcomes.
      RESULTS: On the MR images obtained 6 months postoperatively, 70 patients (89%)
      had a significant reduction in the syrinx with an associated ascent of the
      cerebellar tonsils. Persistent large syringes were treated with reoperation in 6
      patients, and shunts were inserted for hydrocephalus in 2 patients. None of the
      49 patients with curves less than 20 degrees  had progression of their curvature
      postoperatively. Of the 30 patients with curves greater than 25 degrees , 9 had
      no change in the scoliosis or had a reduction in curve magnitude after Chiari
      decompression. This group required no further therapy and was effectively treated
      by Chiari decompression alone. Twenty-one patients required further scoliosis
      treatment after Chiari decompression; 12 required orthotic treatment, 11 received
      spinal instrumentation and fusion surgery, and 2 received orthoses followed by
      fusion and instrumentation. The severity of the curvature beyond 20 degrees  did
      not predict the need for spinal surgery. CONCLUSIONS: This large series reports
      on the efficacy of treatment for scoliosis associated with a CM-I and syrinx in
      children. A CM-I decompression alone was adequate treatment for mild scoliosis of
      less than 20 degrees . Patients with scoliosis greater than 20 degrees  required
      bracing and/or spinal fusion surgery 70% of the time in addition to the CM-I
      decompression.

PMID- 21194284
TI  - Idiopathic syrinx in the pediatric population: a combined center experience.
AB  - OBJECT: Discovery of a syrinx in a child, without a readily identifiable
      proximate cause such as a Chiari malformation, tumor, or site of tethering, is
      often a cause of concern for families and a source of consternation for
      clinicians. There is a paucity of data describing the natural history of an
      idiopathic syrinx in the pediatric population. The authors present the combined
      data of 2 major pediatric neurosurgical centers to describe their experience with
      this condition. METHODS: Data were collected at Children's Hospital Boston and
      St. Louis Children's Hospital according to institutional review board-approved
      protocols and captured visits over a 2.5-year interval (October 2006-March 2009),
      with records reviewed if the patient had a preexisting diagnosis of syrinx.
      Patients were identified by ICD-9 codes derived from departmental databases. All
      pediatric patients (age < 19 years) in whom idiopathic syrinx had been diagnosed,
      as defined by MR imaging findings (dilated central canal in the spinal cord of >=
      1 mm in axial dimension and extending over at least 2 vertebral levels), were
      included. RESULTS: Forty-eight patients met the criteria for idiopathic syrinx
      during this period, and in 32 of them detailed follow-up imaging was available.
      Discovery of a syrinx was incidental in 6 patients, whereas the others were
      referred for imaging because of the presence of pain, neurological symptoms,
      scoliosis, or skin markings. The average age at the first MR imaging session was
      9.7 years, with a mean syrinx size of 4 mm (range 1.2-9.4 mm). The majority (52%)
      of patients had a thoracic syrinx, with the average lesion spanning 7.1 vertebral
      levels. The average follow-up was 23.8 months (range 2-64 months), and subgroups
      of patients with < 3 years and >= 3 years of follow-up were independently
      reviewed. Overall, symptoms improved in 34% and worsened in 9%; 57% of the
      patients remained asymptomatic or stable. Radiographically (in the subgroup of 32
      patients with detailed follow-up imaging), syrinx size decreased in 25% of
      patients, increased in 12.5%, and remained unchanged in 62.5%, with no apparent
      correlation between change in syrinx size and clinical symptoms. CONCLUSIONS:
      Clinically, children with an idiopathic syrinx remained asymptomatic, stable, or
      improved in 91% of cases. The majority of syringes (87.5%) remained stable or
      shrank over time, with no apparent correlation between changes in size and
      changes in symptoms. Although longer follow-up is needed, these data suggest that
      the natural history of an idiopathic syrinx in children is benign, and that
      repeated imaging may not be necessary.

PMID- 21194285
TI  - Morbidity and mortality associated with spinal surgery in children: a review of
      the Scoliosis Research Society morbidity and mortality database.
AB  - OBJECT: Currently, few studies regarding morbidity and mortality associated with
      operative treatment of spinal disorders in children are available to guide the
      surgeon. This study provides more detailed morbidity and mortality data with an
      analysis of 23,918 pediatric cases reported in the multicenter, multisurgeon
      Scoliosis Research Society morbidity and mortality database. METHODS: The
      Scoliosis Research Society morbidity and mortality database was queried for the
      years from 2004 to 2007. The inclusion criterion was age 18 years or younger.
      Cases were categorized by operation type and diagnosis. Details on the surgical
      approach, use of neurophysiological monitoring, and type of instrumentation were
      recorded. Major perioperative complications and deaths were evaluated.
      Statistical analysis was performed with chi-square testing, with a p value < 0.05
      considered significant. RESULTS: A total of 23,918 patients were included. The
      mean age was 13 +/- 3.6 years (+/- SD). Spinal pathology included the following:
      scoliosis (in 19,642 patients), kyphosis (in 1455), spondylolisthesis (in 748),
      trauma (in 478), and other (in 1595 patients). The overall complication rate was
      8.5%. Major complications included wound infections (2.7%), new neurological
      deficits (1.4%), implant-related complications (1.6%), and hematomas (0.4%). The
      most common medical complications were respiratory related (0.9%). Morbidity
      rates differed based on pathology, with patients undergoing treatment for
      kyphosis and spondylolisthesis having higher overall rates of morbidity (14.7%
      and 9.6%, respectively). Patients undergoing revision procedures (2034) or
      corrective osteotomies (2787) were more likely to suffer a complication or new
      neurological deficit. The majority of these deficits improved at least partially.
      Thirty-one deaths were reported for an overall rate of 1.3 per 1000. Respiratory
      complications were the most common cause of mortality (13 cases). Twenty-six of
      the deaths occurred in children undergoing scoliosis correction. CONCLUSIONS:
      Spinal surgery in children is associated with a range of complications depending
      on the type of operation. Mortality rates for all indications and operations were
      low. Patients undergoing more aggressive corrective procedures for deformity are
      more likely to suffer complications and new neurological deficits.

PMID- 21194286
TI  - Retethering of transected fatty filum terminales.
AB  - OBJECT: Untethering of a tethered spinal cord (TSC) by transecting or removing a
      fatty filum terminale is a relatively simple procedure that can prevent or
      ameliorate neurological symptoms, and the postoperative prognosis is usually
      good. Progressive neurological deterioration caused by recurrent tethering has
      been rarely reported. The authors present their experience in cases in which a
      sectioned fatty filum terminale has become retethered. METHODS: The authors
      retrospectively analyzed the surgical results of pediatric patients with fatty
      filum terminale-TSC treated by transection of the filum. The patients' charts
      were reviewed for demographic data, clinical presentation, surgical therapy, and
      follow-up data. RESULTS: Of the 225 children who underwent TSC release by
      sectioning the fatty filum from 1992 to 2005, there were 6 patients (2.7%; 3
      males, 3 females) in whom the fatty filum retethered. The mean age at the first
      diagnosis of TSC was 5.2 years (range 2 months-12.3 years). The mean duration
      from the first untethering procedure to retethering was 5.4 years. The mean age
      at the time of retethering was 10.6 years (range 7-17.5 years). Symptoms of
      retethering were urinary incontinence, low-back pain, difficulty walking,
      constipation, leg pain, and worsening foot deformity. Patients underwent
      cystometrography at the time retethering was indicated by increased bladder
      capacity, large post-void residual volume, decreased bladder capacity, increase
      in filling pressure, and poor sensation of filling. Magnetic resonance imaging
      revealed adherence of the rostral stump of the sectioned filum to the midline
      dorsal dural surface. All patients underwent the second untethering procedure.
      Four patients improved neurologically and experienced no retethering thereafter
      (mean follow-up period 5.5 years). Two patients experienced additional
      retethering after temporary improvement following the second untethering
      procedure. CONCLUSIONS: Retethering of the spinal cord is a rare condition
      occurring after the sectioning of a fatty filum terminale. Awareness of this rare
      sequela is necessary for appropriate long-term management of TSC caused by a
      fatty filum terminale. Cystometrography is useful for detecting the lesion and
      confirming the diagnosis of retethering.

PMID- 21194287
TI  - Harvey Cushing and early spinal dysraphism repair at Johns Hopkins Hospital.
AB  - As neurological surgery began developing into a surgical subspecialty in the US
      at the turn of the 20th century, with Harvey Cushing at the forefront, the
      operative treatment of spinal dysraphism was refined with attempts to minimize
      complications. Following institutional approval, and through the courtesy of the
      Alan Mason Chesney Archives, the authors reviewed the Johns Hopkins Hospital
      surgical files from 1896 to 1912. Patients presenting with spinal dysraphism who
      underwent surgical intervention by Dr. Harvey Cushing were selected for further
      analysis. Ten patients presented for surgical intervention for spinal dysraphism,
      and 7 of these had concurrent hydrocephalus. The mean age of these patients was
      5.8 months (range 1-14 months). The mean length of stay was 20.4 days. There were
      6 inpatient deaths. At the time of last follow-up, 2 patients were well, 1
      patient remained unimproved, and 1 patient (for whom no discharge outcome was
      available) had died. The cases described in detail offer insight into the breadth
      of Cushing's practice and the varied approaches he employed. The use of Faradic
      stimulation to assess nerve root function, the use of complex multilayered
      closures, and the creation of operative tables for combined treatment of
      hydrocephalus and spinal dysraphism illustrate Cushing's contributions to
      developing the field of pediatric neurosurgery.

PMID- 21194288
TI  - Posterior fossa craniotomy for trapped fourth ventricle in shunt-treated
      hydrocephalic children: long-term outcome.
AB  - OBJECT: Trapped fourth ventricle (TFV) is a rare late complication of
      postinfectious or posthemorrhagic hydrocephalus. This entity is distinct from a
      large fourth ventricle because TFV entails pressure in the fourth ventricle and
      posterior fossa due to abnormal inflow and outflow of CSF, causing significant
      symptoms and signs. As TFV is mostly found in children who were born prematurely
      and have cerebral palsy, diagnosis and treatment options are a true challenge.
      METHODS: Between February 1998 and February 2007, 12 children were treated for
      TFV in Dana Children's Hospital by posterior fossa craniotomy/craniectomy and
      opening of the TFV into the spinal subarachnoid space. The authors performed a
      retrospective analysis of relevant data, including pre- and postoperative
      clinical characteristics, surgical management, and outcome. RESULTS: Thirteen
      fenestrations of trapped fourth ventricles (FTFVs) were performed in 12 patients.
      In 6 patients with prominent arachnoid thickening, a stent was left from the
      opened fourth ventricle into the spinal subarachnoid space. One patient underwent
      a second FTFV 21 months after the initial procedure. No perioperative
      complications were encountered. All 12 patients (100%) showed clinical
      improvement after FTFV. Radiological improvement was seen in only 9 (75%) of the
      12 cases. The follow-up period ranged from 2 to 9.5 years (mean 6.11 +/- 2.3
      years) after FTFV. CONCLUSIONS: Fenestration of a TFV via craniotomy is a safe
      and effective option with a very good long-term outcome and low rate of
      morbidity.

PMID- 21194289
TI  - The effectiveness of ventriculocystocisternostomy for suprasellar arachnoid
      cysts.
AB  - OBJECT: The aim of this study was to report the long-term outcomes of patients
      receiving endoscopic ventriculocystocisternostomy (VCC) for suprasellar arachnoid
      cysts (SACs), and to analyze all published reports on outcomes of
      ventriculocystostomy (VC) versus VCC to compare the effectiveness of the 2
      techniques. METHODS: Eleven consecutive patients with previously untreated SACs
      were surgically treated using endoscopic VCC. Another 2 patients were treated
      with VCC following ventriculoperitoneal shunt placement. Clinical imaging data
      were recorded. An analysis was performed of all published patient outcomes
      following endoscopic VC or VCC for an SAC. RESULTS: Developmental delay and
      progressive macrocephaly were the most common preoperative symptoms. At a mean
      clinical follow-up interval of 63 months, 10 of 11 patients undergoing primary
      VCC did not require reoperation. An analysis of the literature suggests that VCC
      may be more effective than VC. Of the 44 reported patients that underwent VC as a
      first treatment, 7 (16%) required reoperation, and 7 (8%) of 86 patients who
      underwent VCC as a first treatment required reoperation. When VC or VCC was
      performed following a prior surgical procedure, 4 of 11 patients undergoing VC
      had a treatment failure requiring reoperation. In contrast, only 2 of the 17
      reported cases of VCC following a prior procedure required further treatment. The
      difference in reoperation rates following either primary or secondary VC was
      significantly higher than following primary or secondary VCC (p = 0.04).
      CONCLUSIONS: The authors conclude that VCC is an effective and durable treatment
      for symptomatic SACs in most cases.

PMID- 21194290
TI  - Association of bacteria with hydrocephalus in Ugandan infants.
AB  - OBJECT: Infantile hydrocephalus in East Africa is predominantly postinfectious.
      The microbial origins remain elusive, since most patients present with
      postinfectious hydrocephalus after antecedent neonatal sepsis (NS) has resolved.
      METHODS: To characterize this syndrome in Ugandan infants, the authors used
      polymerase chain reaction targeting bacterial 16S ribosomal DNA from CSF to
      determine if bacterial residua from recent infections were detectable. Bacteria
      were identified based on the relationship of genetic sequences obtained with
      reference bacteria in public databases. The authors evaluated samples from
      patients presenting during dry and rainy seasons and performed environmental
      sampling in the villages of patients. RESULTS: Bacterial DNA was recovered from
      94% of patients. Gram-negative bacteria in the phylum Proteobacteria were the
      most commonly detected. Within this phylum, Gammaproteobacteria dominated in
      patients presenting after infections during the rainy season, and
      Betaproteobacteria was most common following infections during the dry season.
      Acinetobacter species were identified in the majority of patients admitted after
      rainy season infection. CONCLUSIONS: Postinfectious hydrocephalus in Ugandan
      infants appears associated with predominantly enteric gram-negative bacteria.
      These findings highlight the need for linking these cases with antecedent NS to
      develop more effective treatment and prevention strategies.

PMID- 21194291
TI  - Encephalocele in Uganda: ethnic distinctions in lesion location, endoscopic
      management of hydrocephalus, and survival in 110 consecutive children.
AB  - OBJECT: This study characterizes the first clinical series of encephalocele (EC)
      from East or Central Africa, and is the largest reported from the African
      continent. The authors explored survival, the efficacy of primary endoscopic
      management of associated hydrocephalus, and ethnic differences in EC location.
      METHODS: One hundred ten consecutive children presented to CURE Children's
      Hospital of Uganda for treatment of EC over a 9-year period. Clinical data,
      including patient demographic information, birth date, lesion type (sincipital,
      parietal, or occipital), operative data, and subsequent course had been entered
      prospectively into a clinical database. Home visits to update the status of those
      lost to follow-up were done when possible. With appropriate institutional
      approvals, the database was reviewed for this retrospective study. Two-tailed
      probability values calculated using the Fisher exact test were used to assess the
      significance of differences among groups, with p < 0.05 being considered
      significant. The Kaplan-Meier method was used for analysis of survival and
      treatment success probabilities. RESULTS: There were 53 (48%) occipital, 33 (30%)
      sincipital, and 24 (22%) parietal lesions. Occipital lesions were significantly
      more common among children of Bantu origin (p = 0.02). Nilotes demonstrated a
      roughly equal distribution among sincipital, parietal, and occipital locations.
      The female/male ratio was 1.2, with no difference between EC types (range 1.0
      1.4, p = 0.6-0.8). Of 110 patients, 108 (98%) underwent surgical repair at a
      median age of 1 month (mean 15.7 months), whereas 2 had treatment for
      hydrocephalus only. Wound revision was required in 13% of cases. Surgery-related
      mortality was 3%. One-year and 5-year survival rates were 87% (95% CI 0.79-0.93)
      and 61% (95% CI 0.51-0.70), respectively. Hydrocephalus required treatment in
      32%, and was equally common among the 3 EC types. Thirteen patients were treated
      with combined endoscopic third ventriculostomy/choroid plexus cauterization
      (ETV/CPC) and 2 with ETV alone, whereas 18 patients received primary shunt
      placement. Predicted treatment success at 1 year was 79% for ETV or ETV/CPC (95%
      CI 0.50-0.94) and 47% for shunt placement (95% CI 0.24-0.71). CONCLUSIONS:
      Analysis of this first EC series from this region suggests that sincipital
      lesions are 3 times more common in East than in West Africa. Occipital lesions
      predominate in patients of Bantu origin, but not among those of Nilotic descent.
      Hydrocephalus incidence was equally common among different EC types, and
      endoscopic treatment was more successful (79%) than shunting (47%) at 1 year. The
      5-year mortality rate was similar to that for infants with myelomeningocele in
      Uganda, and more than twice that for their unaffected peers.

PMID- 21194292
TI  - A rare case of malignant pediatric ectomesenchymoma arising from the falx
      cerebri.
AB  - Malignant ectomesenchymoma is a rare tumor arising from mature ganglion cells
      with immature myogenous elements, with only 4 pediatric intracranial cases having
      been previously reported. The authors report a rare case of intracranial
      malignant ectomesenchymoma originating from the falx cerebri in a 10-year-old
      boy. The patient presented with a 2-week history of headache, nausea, and blurry
      vision, with mild lateral gaze diplopia. A CT scan revealed a solitary 7.2 * 3.8
      cm dural-based mass that extended along the falx. No metastatic disease was
      identified, and the lesion was grossly resected without complication.
      Pathological investigation identified single and small groups of cells in a
      myxoid background, with polygonal or spindle-shaped cells containing eccentric
      nuclei and prominent nucleoli. Immunohistochemical staining of some cells was
      positive for smooth-muscle actin, CD99, and vimentin, whereas other cells (often
      process forming) were positive for S100 protein, synaptophysin, and neurofilament
      protein. Staining was negative for CD138, CD45, alpha-fetoprotein, CK AE1/3,
      glial fibrillary acidic protein, CK7, CK20, CD31, CD34, myoD, and desmin. Normal
      immunopositivity was seen for INI-1. The Ki 67 immunostaining had < 25%
      reactivity. The patient was treated with a sarcoma-based chemotherapy regimen and
      radiation to the craniospinal axis, and was found to be without recurrence or
      metastatic disease at 20 months.

PMID- 21194293
TI  - Transcallosal interforniceal approach to pineal region tumors in 150 children.
AB  - OBJECT: Pediatric pineal region tumors are very difficult to cure surgically. The
      authors used the transcallosal interforniceal approach in patients with these
      lesions. METHODS: One hundred fifty children, 98 boys and 52 girls, with pineal
      region tumors underwent tumor resection via the transcallosal interforniceal
      approach in the pediatric neurosurgery ward of TianTan Hospital. The patients
      ranged in age from 1 to 15 years. Fifty-eight patients had mature teratomas; 57,
      immature teratomas; 14, astrocytomas; 3, glioblastomas; 4, pineoblastomas; 2,
      pineocytomas; 4, choriocarcinomas; 4, cavernous hemangiomas; 2, germ cell tumors;
      and 2, epidermoid cysts. RESULTS: One hundred twenty-nine tumors were totally
      removed, 15 were subtotally removed, and 6 were partly removed. There were no
      deaths and no subsequent instances of disconnection syndrome. Short-term memory
      deficits appeared in 94 patients but resolved within 6 months in most; only a few
      patients retained persistent deficits. There were 2 patients with mutism that
      resolved within 10 days. Parinaud syndrome was observed in 45 patients after
      surgery; 21 of these cases had appeared preoperatively. The syndrome resolved
      within 6 months in 31 patients, while it remained in the other 14. CONCLUSIONS:
      The transcallosal interforniceal approach appears to be a safe route for pineal
      region tumors in children, and complete resection can be achieved in the majority
      of patients.

PMID- 21194294
TI  - Small-ventricle neuroendoscopy for pediatric brain tumor management.
AB  - OBJECT: The use of intraventricular endoscopy to achieve diagnosis or to resect
      accessible intraventricular or paraventricular tumors has been described in the
      literature in both adults and children. Traditionally, these techniques have not
      been used in patients with small ventricles due to the perceived risk of greater
      morbidity. The authors review their experience with the effectiveness and safety
      of endoscopic brain tumor management in children with small ventricles. METHODS:
      Between July 2002 and December 2009, 24 children with endoscopically managed
      brain tumors were identified. Radiological images were reviewed by a radiologist
      blinded to study goals and clinical setting. Patients were categorized into small
      ventricle and ventriculomegaly groups based on frontal and occipital horn ratio.
      Surgical success was defined a priori and analyzed between groups. Trends were
      identified in selected subgroups, including complications related to pathological
      diagnosis and surgeon experience. RESULTS: Six children had small ventricles and
      18 had ventriculomegaly. The ability to accomplish surgical goals was
      statistically equivalent in children with small ventricles and those with
      ventriculomegaly (83% vs 89%, respectively, p = 1.00). There were no
      complications in the small-ventricle cohort, but in the ventriculomegaly cohort
      there were 2 cases of postoperative hemorrhages and 1 case of infection. All
      hemorrhagic complications occurred in patients with high-grade tumor
      histopathological type and were early in the surgeon's endoscopic career.
      CONCLUSIONS: Based on our experience, endoscopy should not be withheld in
      children with intraventricular tumors and small ventricles. Complications appear
      to be more dependent on tumor histopathological type and surgeon experience than
      ventricular size.

PMID- 21194295
TI  - The "swing-ding": a golf-related head injury in children.
AB  - OBJECT: In recent years there has been an increased incidence of golf-associated
      head injuries in children and adolescents. At the authors' institution, they have
      identified a unique pattern of head injury associated with a swinging golf club.
      In this study, the authors highlight the mechanism of this injury and report
      their experience treating it. METHODS: The authors reviewed the database of
      Rainbow Babies and Children's Hospital Trauma Center and performed a
      retrospective analysis of golf injuries recorded over a 10-year period (January
      2000-April 2010). They identified 13 children (9 boys and 4 girls) who sustained
      head injuries in golfing accidents. All patients were 10 years of age or younger.
      The medical charts were reviewed and follow-up interviews were conducted to
      better delineate the details of the injuries. RESULTS: Injuries included 13
      depressed skull fractures, 7 epidural hematomas, and 1 cerebral contusion. All 13
      patients sustained their injuries after being struck in the head by a golf club.
      Seven sustained injuries on the follow-through of the initial swing and 3
      sustained injuries on the backswing. All but one patient required neurosurgical
      intervention. Five patients developed neurological sequelae. None of the children
      had prior experience with golf equipment. All but one injury occurred in the
      child's own backyard. There was no direct supervision by an adult in any of the
      cases. CONCLUSIONS: Golfing can lead to serious head injuries in children. The
      authors noticed a unique pattern of golf-related head injuries, previously not
      described, that they have termed the "swing-ding." This golf club-inflicted
      injury occurs when a child stands too close to a swinging golfer and is struck in
      the head, subsequently sustaining a comminuted depressed skull fracture in the
      frontal or temporal region, with or without further intracranial injury. The
      study suggests that a lack of adult supervision, minimal previous golf
      experience, and proximity of the child to the swinging golfer are all implicated
      in this head injury pattern.

PMID- 21194296
TI  - Skull-fixated fiducial markers improve accuracy in staged frameless stereotactic
      epilepsy surgery in children.
AB  - OBJECT: Surgery to monitor and resect epileptogenic foci may be undertaken in 2
      stages, providing an opportunity to use skull-fixated fiducials implanted during
      the first stage to improve the accuracy of cortical resection during the second
      stage. This study compared the intrinsic accuracy of skin-based and skull-fixated
      fiducial markers in registering frameless stereotaxy during pediatric epilepsy
      surgery. To the authors' knowledge, these modalities of registration have not
      previously been directly compared in this population. METHODS: The authors
      undertook a retrospective review of pediatric patients who underwent resection of
      epileptogenic foci in 2 stages with frameless stereotactic assistance, performed
      by a single surgeon at Oregon Health & Science University. For the first stage
      (subdural grid implantation), 9 skin fiducial markers were used to register
      anatomical data in a frameless stereotactic station. Intraoperatively, four 3-mm
      screws were placed circumferentially around the craniotomy. Postoperatively, thin
      slice brain MR and CT images were obtained and fused. For the second stage, the 4
      screws were used as fiducial markers to register the stereotactic anatomical
      data. For both stages, accuracy (difference in millimeters from zero of the
      manual fiducial registration compared with the computer model) was determined
      using navigation software. The intrinsic accuracy of these 2 methods of fiducial
      registration was compared using a paired Student t-test. RESULTS: Between 2004
      and 2009, 40 pediatric patients with epilepsy underwent frameless stereotactic
      surgical procedures. Fourteen patients who had 2-stage procedures using skin
      based and skull-fixated registration with complete accuracy data were included in
      this retrospective review. Mean registration error was significantly lower using
      skull-fixated fiducials (1.35 mm, 95% CI 1.09-1.60 mm) than using skin-based
      fiducials (1.85 mm, 95% CI 1.56-2.13 mm; p = 0.0016). CONCLUSIONS: A
      significantly higher degree of accuracy was achieved using 4 skull-fixated
      fiducials compared with using 9 skin-based fiducials. This simple and accurate
      method for registering frameless stereotactic anatomical data does not involve
      the potential time, expense, discomfort, and morbidity of extraoperative skull
      fixated fiducial placement. The method described in this paper could also be
      extrapolated to other planned 2-stage cranial surgical procedures such as
      combined skull base approaches.

PMID- 21194297
TI  - Therapeutic effect of photodynamic therapy using Na-pheophorbide a on
      osteomyelitis models in rats.
AB  - OBJECTIVE: In this study, we examined the therapeutic effect of photodynamic
      therapy (PDT) using the photosensitizer Na-Pheophorbide a (Na-Phde a) on
      osteomyelitis models in rats. BACKGROUND: Osteomyelitis is one of the most
      serious infectious problems in the orthopedic field. Recently, as a new clinical
      approach against septic arthritis, an experimental in vivo and in vitro model for
      the inactivation of methicillin-resistant-Staphylococcus aureus by PDT using Na
      Phde a has been developed. METHODS: Methicillin-sensitive Staphylococcus aureus
      (MSSA) was injected into the tibia of the rats to create osteomyelitis models (n
      = 10, 10 legs). A total of 560 MUmol/l of Na-Phde a solution was injected into
      five of these tibial osteomyelitis models (five legs) 48 h after the initial MSSA
      infection. Sixty minutes after the Na-Phde a injection, a semiconductor laser
      (125 mW, 670 nm) was used to irradiate the models for 10 min with a total energy
      of 93.8 J/mm(2). As a control group, five rats (five legs) were treated with a
      phosphate buffered saline injection at 48 h after MSSA infection. Weight and leg
      perimeter changes were plotted. Bacterial growth, histological examination and
      radiological examination were evaluated at 14 days after initial treatment.
      RESULTS: PDT with Na-Phde a significantly prevented leg swelling. In the PDT
      group, bone destruction owing to osteomyelitis was inhibited not only
      histologically but also radiographically. CONCLUSIONS: The results in these
      experiments show that PDT using Na-Phde a improved osteomyelitis in rats. This
      suggests that PDT using Na- Phde a can be a useful treatment for osteomyelitis.

PMID- 21194298
TI  - Validation of the use of peripheral blood mononuclear cells as surrogate model
      for skeletal muscle tissue in nutrigenomic studies.
AB  - Peripheral blood mononuclear cells (PBMCs) offer a significant promise for gene
      expression analyses as a substitute for tissues that are not easily accessible.
      The objective of this study was to validate the use of PBMCs for gene expression
      analysis as a marker of nutritional intervention as an alternative to skeletal
      muscle tissue (SMT) biopsies. We performed a transcriptome comparison of PBMCs
      versus SMT after an 8-week supplementation with n-3 polyunsaturated fatty acid
      (PUFA) in 16 obese and insulin-resistant subjects. Expression levels of 48,803
      transcripts were assessed by the Human-6 v3 Expression BeadChips (Illumina, San
      Diego, CA). In SMT, 36,738 (75%) transcripts were detected, whereas 34,182 (70%)
      transcripts were detected in PBMCs. Further, 88% (32,341) of these transcripts
      were coexpressed in both tissues. Importantly, a strong correlation (r = 0.84, p
      < 0.0001) was observed between transcript expression levels of PBMCs and SMT
      after n-3 PUFA supplementation. In conclusion, PBMCs express the majority of
      transcripts expressed in SMT subsequent to n-3 PUFA supplementation and their
      expression levels are comparable. In the interest of practicalities and cost,
      these results support the use of PBMCs as a surrogate model for SMT gene
      expression in nutrigenomic studies. Further research on PBMC and SMT gene
      expression in response to other nutritional exposures is warranted.

PMID- 21194299
TI  - Functional homogeneity in microRNA target heterogeneity--a new sight into human
      microRNomics.
AB  - MicroRNomics is a novel genomics that studies the identification, targets,
      biological functions, etc., of microRNAs (miRNAs) on a genomic scale.
      Computational target prediction algorithms are important applications in
      microRNomics. However, the overlaps between target sets predicted by different
      algorithms for one miRNA are often small. Our work is initiated to find the
      reasons causing "heterogeneity" and investigate whether the heterogeneous targets
      are homogeneous on functional levels by integrating similarity metrics. The
      results suggest that most human miRNAs own heterogeneous targets. The
      dissimilarity of thermodynamic characteristics and the different treatment of 3'
      compensatory sites adopted by algorithms are the main reasons for target
      "heterogeneity." Meanwhile, we find most miRNA heterogeneous targets are
      functional homogeneity because of the common principles such as sites
      conservation and G:U wobble pairs in different algorithms. Our findings reveal
      the "functional homogeneity in miRNA target heterogeneity." The conclusions
      provide a perspective of microRNomics on functional levels, which introduce a new
      sight into human miRNA targets.

PMID- 21194300
TI  - -8p12-23 and +20q are predictors of subtypes and metastatic pathways in
      colorectal cancer: construction of tree models using comparative genomic
      hybridization data.
AB  - A substantial body of evidence suggests the genetic heterogeneous pattern and
      multiple pathways in colorectal cancer initiation and progression. In this study,
      we construct a branching tree and multiple distance-based tree models to
      elucidate these genetic patterns and pathways in colorectal cancer by using a
      data set comprised of 244 cases of comparative genomic hybridization. We identify
      the six most common gains of chromosomal regions of 7p (37.0%), 7q11-32 (34.8%),
      8q (48.3%), 13q (49.1%), 20p (36.1%), and 20q (50.4%), and the nine most common
      losses of 1p13-36 (30.9%), 4p15 (24.3%), 4q33-34 (24.3%), 8p12-23 (50.9%), 15q13
      14 (23.5%), 15q24-25 (24.3%), 17p (34.8%), 18p (36.5%), and 18q (61.7%) in
      colorectal cancer. We classify colorectal cancer into two distinct groups: one
      preceding with -8p12-23, and the other with +20q. The sample-based classification
      tree also demonstrates that colorectal cancer can be classified into multiple
      subtypes marked by -8p12-23 and +20q. By comparing chromosomal abnormalities
      between primary and metastatic colorectal cancer, we identify five potential
      metastatic pathways: (-18q, -18p), (-8p12-23, -4p15, -4q33-34), (+20q, +20p),
      (+20q, +7p, +7q11-32), and +8q. -8p12-23 and +20q are inferred to be the two
      marker events of colorectal cancer metastasis. The current oncogenetic tree
      models may contribute to our understanding towards molecular genetics in
      colorectal cancer. Particularly, the metastatic pathways we describe may provide
      pivotal clues for metastatic candidate genes, and thus impact on the prediction
      and intervention of metastatic colorectal cancer.

PMID- 21194301
TI  - Perceptions of discrimination among Mexican American families of seriously ill
      children.
AB  - This paper describes Mexican American family members' descriptions of perceived
      discrimination by pediatric health care providers (HCPs) and the families'
      reactions to the HCPs' discriminatory conduct. A retrospective, grounded theory
      design guided the overall study. Content analysis of interviews with 13
      participants from 11 families who were recruited from two children's hospitals in
      Northern California resulted in numerous codes and revealed that participants
      perceived discrimination when they were treated differently from other, usually
      white, families. They believed they were treated differently because they were
      Mexican, because they were poor, because of language barriers, or because of
      their physical appearance. Participants reported feeling hurt, saddened, and
      confused regarding the differential treatment they received from HCPs who parents
      perceived "should care equally for all people." They struggled to understand and
      searched for explanations. Few spoke up about unfair treatment or complained
      about poor quality of care. Most assumed a quiet, passive position, according to
      their cultural norms of respecting authority figures by being submissive and not
      questioning them. Participants did not perceive all HCPs as discriminatory; their
      stories of discrimination derived from encounters with individual nurses or
      physicians. However, participants were greatly affected by the encounters, which
      continue to be painful memories. Despite increasing efforts to provide culturally
      competent palliative care, there is still need for improvement. Providing
      opportunities for changing HCPs' beliefs and behaviors is essential to developing
      cultural competence.

PMID- 21194302
TI  - An approach to diabetes mellitus in hospice and palliative medicine.
AB  - Abstract Hospice and palliative medicine practitioners frequently encounter
      diabetes and associated complications as comorbidities in end-of-life patients.
      As the patient with diabetes approaches end-of-life, there comes a time when
      tight glycemic control can not only prove of questionable benefit, but has the
      potential to cause harm. The medical literature offers little guidance on
      managing these complications appropriately. This article identifies three
      distinct classifications of patients with diabetes approaching the ends of their
      lives due to advanced illnesses. The authors propose a specific framework to
      guide management in patients with diabetes and advanced disease who are
      relatively stable, experiencing impending death or organ failure, or actively
      dying. The authors provide comprehensive information on commonly used diabetic
      medications, with necessary considerations and dose adjustments for these
      populations. The goal of the approach is to address individual patient needs,
      provide guidance for patients and caregivers, and ultimately maximize outcomes
      for patients with diabetes in the palliative care setting.

PMID- 21194303
TI  - Demographic and clinical determinants of having do not resuscitate orders in the
      intensive care unit of a comprehensive cancer center.
AB  - To understand the needs of patients and family members as physicians communicate
      their expectations about patients admitted to the intensive care unit (ICU), we
      evaluated the demographic and clinical determinants of having a Do Not
      Resuscitate (DNR) order for adults with cancer. Patients included were admitted
      from June 16, 2008-August 16, 2008, to the ICU in a comprehensive cancer center.
      We conducted a prospective chart review and collected data on patient
      demographics, length of stay, advance directives, clinical characteristics, and
      DNR orders. A total of 362 patients met the inclusion criteria; only 15.2% had
      DNR orders before ICU discharge. In the multivariate analysis, we found that
      medical admission was an independent predictor of having a DNR order during the
      ICU stay (odds ratio = 3.65; 95% confidence interval, 1.44-9.28); we also found a
      significant two-way interaction between race/ethnicity and type of admission
      (medical vs. surgical) with having a DNR order (p = .04). Although medical
      admissions were associated with significantly more DNR orders than were surgical
      admissions, we observed that the subgroup of non-white patients admitted for
      medical reasons was significantly less likely to have DNR orders. This finding
      could reflect different preferences for aggressive care by race/ethnicity in
      patients with cancer, and deserves further investigation.

PMID- 21194304
TI  - The role of laparoscopic approach for anastomotic leakage after minimally
      invasive surgery for colorectal cancer.
AB  - OBJECTIVES: The objectives of this study were to evaluate the feasibility and
      safety of a re-laparoscopic approach to manage anastomotic leakage after
      minimally invasive colorectal resection and to compare its clinical outcomes with
      those obtained using an open approach. METHODS: We retrospectively reviewed
      clinical data from 1714 patients who underwent colorectal cancer resection from
      September 2006 to August 2009 at the Korea University Medical Center. Clinical
      data from a total of 57 surgery patients who developed anastomotic leakage were
      analyzed. RESULTS: Twenty-six leakage cases were managed laparoscopically,
      whereas the remaining 31 leakage cases were managed using an open approach. There
      were no significant differences in age, sex, or other clinical features between
      patients in the two groups. The total operation time was shorter in the
      laparoscopic group (107.3 +/- 68.1 minutes) than in the open group (126.5 +/-
      50.1 minutes), but this difference was not statistically significant (P = .230).
      Six cases in each group required additional procedures such as reoperation or
      percutaneous intervention (P = .126). There was one case of postoperative
      mortality in the open group. Median (quartiles 25%-75%) number of days required
      to resume a soft diet tended to be shorter in the laparoscopic group than the
      open group (5 [3-7] versus 6 [5-10] days; P = .057). Patients in both groups
      showed similar postoperative complications including intraabdominal abscess;
      however, the incidence of wound infection was significantly lower in the
      laparoscopic group than the open group (3.8% versus 25.8%; P = .031).
      CONCLUSIONS: Compared with conventional open treatment of anastomotic leakage,
      the laparoscopic approach resulted in fewer wound complications and tendency of
      early recovery of bowel movement without an increase in adverse outcomes. Using a
      laparoscopic approach, all the advantages of minimally invasive surgery can be
      realized in patients who develop anastomotic leakage after minimally invasive
      surgery.

PMID- 21194305
TI  - Single-incision laparoscopic cholecystectomy versus conventional laparoscopic
      cholecystectomy: a retrospective comparative study.
AB  - BACKGROUND: Recent reports have suggested that single-incision laparoscopic
      cholecystectomy (SILC) is technically feasible. We present our initial
      retrospective comparative study between SILC and conventional laparoscopic
      cholecystectomy (CLC) with respect to perioperative outcomes. METHODS: The
      authors reviewed 100 SILC and 100 CLC performed by a single surgeon from May 2009
      to July 2010 at the Shengjing Hospital of China Medical University. All the
      procedures were completed by using the standard trocars and rigid laparoscopic
      instruments. Demographic data, operating time, estimated blood loss, analgesics
      requirements, days to oral food intake, and complications were compared. RESULTS:
      Of the attempted SILC cases, 99 cases (99%) were successfully performed, with 1
      case requiring three additional trocars for safe dissection because of existence
      of accessory bile duct. In the CLC group, all the procedures were successfully
      completed (three trocars) without conversion to open cholecystectomy. Compared
      with the CLC group, there was a lower mean estimated blood loss (17.9 +/- 15.8 mL
      versus 27.5 +/- 13.9 mL; P = .000) and analgesic requirement (10 versus 23; P =
      .024) in the SILC group. However, there was no difference between SILC and CLC in
      operating time (53.5 +/- 24.0 minutes versus 49.2 +/- 13.8 minutes; P = .163),
      days to oral food intake (1.8 +/- 0.8 days versus 1.8 +/- 0.7 days; P = .873),
      and postoperative complication rate (2% versus 0%; P = .155). CONCLUSION: SILC is
      feasible using the standard trocars and rigid laparoscopic instruments, and it is
      an effective alternative to CLC in selected patients. However, further clinical
      studies are necessary to confirm its real benefits.

PMID- 21194306
TI  - Percutaneous endoscopic gastrostomy placement in a human immunodeficiency virus
      positive pediatric population leads to an increase in minor complications.
AB  - AIM: The development of effective multiple drug regimens for treating human
      immunodeficiency virus (HIV) are associated with nonadherence in children. HIV
      positive children also have a higher incidence of malnutrition. Placement of a
      percutaneous endoscopic gastrostomy (PEG) is a potential solution. Primary
      outcome was to determine the complications of PEG placement in a pediatric HIV
      positive population. MATERIALS AND METHODS: A 10 year retrospective data analysis
      was carried out on all HIV-positive children undergoing insertion of a PEG at two
      institutions. Parameters examined included infections, leakage, displacement,
      reasons for removal, total time in situ, HIV stage, CD4 count, and serological
      investigation. Data were compared against published data for PEG insertion in
      pediatric oncology patients and other comparable pediatric series using Fisher's
      exact test. RESULTS: Eighteen children were identified, with a median age 35
      months and follow-up of 62 months. The majority of patients had advanced disease
      (Stage C; 65%). Fifty percent of PEGs were inserted for feeding supplementation
      and all were used for the administration of medications. Sixty-one percent
      experienced a minor complication; 5/18 (27.7%) experienced peristomal infection;
      2/18 (11.1%) experienced either bleeding, leakage, or excessive granulation; and
      1/18 (5.6%) experienced dislodgement. Stage of HIV did not affect the incidence
      of bleeding or infection: 5/11(Stage C) versus 2/7(Stage B) (P = .3). There was
      no significant difference for major complications when compared with any series
      though comparison with a large pediatric series revealed a significant difference
      for minor complications 11/18 versus 27/120 (P = .0003). CONCLUSIONS: There is a
      low rate of serious complications with PEG insertion in our patients, and the
      rate is comparable to that seen in pediatric oncology patients. The minor
      complication rate is, however, higher than a nonimmune compromised population;
      and careful follow-up for these patients is recommended so that the appropriate
      therapy can be promptly initiated.

PMID- 21194307
TI  - Do new guidelines and technology make the routine pelvic examination obsolete?
AB  - Routine pelvic examinations are the core of the periodic gynecological
      examination and widely tolerated as a necessary part of health maintenance. Is
      this examination beneficial for asymptomatic women? Justifications for the pelvic
      examination include screening for Chlamydia (or gonorrhea) infection, evaluation
      before initiation of hormonal contraception, screening for cervical cancer, and
      early detection of ovarian cancer. Current nucleic acid amplification tests for
      Chlamydia and gonorrhea permit the use of urine and self-administered vaginal
      swabs, which most women prefer over a pelvic examination. Pelvic examination
      findings do not affect the decision to prescribe or withhold systemic hormonal
      contraception; a pelvic examination is not needed to initiate these
      contraceptives. Recent American College of Obstetricians and Gynecologists (ACOG)
      guidelines recommend less frequent cervical screening, thus decreasing the
      frequency of a speculum examination for cervical screening. Bimanual examinations
      for palpation of the uterus and ovaries are also routinely performed in the
      United States. Clinical trial data, however, show these examinations do not lead
      to earlier detection of ovarian cancer. No evidence identifies benefits of a
      pelvic examination in the early diagnosis of other conditions in the asymptomatic
      woman. Speculum and bimanual examinations are uncomfortable, disliked by many
      women, and use scarce time during a well woman visit. Eliminating the speculum
      examination from most visits and the bimanual examination from all visits of
      asymptomatic women will free resources to provide services of proven benefit.
      Overuse of the pelvic examination contributes to high healthcare costs without
      any compensatory health benefit.

PMID- 21194308
TI  - Evidence against a link between hyperemesis gravidarum and personality
      characteristics from an ethnically diverse sample of pregnant women: a pilot
      study.
AB  - BACKGROUND: Hyperemesis gravidarum (HG), a pregnancy-related condition marked by
      extreme nausea and vomiting, has been considered a psychosomatic illness
      associated with long-standing personality characteristics (e.g., hysteria). In
      this pilot study, we examined personality, somatic, and psychological variables
      with ethnically diverse samples of women with HG and women with typical levels of
      nausea and vomiting of pregnancy (NVP). METHODS: Personality (Minnesota
      Multiphasic Personality Index-2 [MMPI-2] and MMPI-2RF), somatic (MMPI-2RF), and
      psychological (Beck Depression Inventory-II [BDI-II] and NVP-related quality of
      life) variables collected during the first trimester of pregnancy were compared
      between 15 women with HG and 15 women with normal levels of NVP matched for age,
      education, marital status, insurance source, and race/ethnicity. A secondary
      analysis was performed comparing these variables among a group of 9 asymptomatic
      pregnant women to the HG and NVP groups. RESULTS: No significant differences were
      found between the HG and NVP groups on any personality, somatic, or psychological
      variables. Both groups had clinically significant elevations on the MMPI-2
      hypochondriasis scale, which incorporates somatic symptoms. The NVP group had a
      clinically significant elevation on the MMPI-2RF gastrointestinal complaints
      scale. Both groups had significantly higher means on the MMPI-2 and MMPI-2RF
      scales than the asymptomatic group. Predominantly Spanish speakers appeared
      particularly vulnerable to psychological distress associated with somatic
      complaints. CONCLUSIONS: The results of this pilot study suggest that research
      with HG patients is feasible and that psychological distress expressed by women
      with HG and NVP may reflect reactions to somatic symptoms. No evidence was found
      to support an association between HG and personality characteristics.
      Recommendations for future research are provided, such as examining the potential
      benefits of translation services for Spanish-speaking HG patients.

PMID- 21194309
TI  - Factors associated with sexually transmitted infection underreporting among
      female sex workers in China.
AB  - OBJECTIVE: To examine the underreporting of sexually transmitted infections (STI)
      (i.e., no STI by self-report but have at least one STI through biological testing
      or clinical examination) and factors associated with underreporting among female
      sex workers (FSWs) in China. METHODS: A total of 454 FSWs were recruited from
      entertainment establishments in a rural county of Guangxi, China. Participants
      completed a self-administered survey about their demographic and working
      characteristics, history of STI (past or current infections), sexual history and
      practices, and HIV/STI-related knowledge and perceptions; 411 of the sample were
      also tested for syphilis, Neisseria gonorrheae, Chlamydia, Trichomonas, and
      genital warts. RESULTS: About 18% (79 of 411) of the sample reported a history of
      STI (past or current infections). Biological testing or clinical examination
      revealed at least one STI (acute STI) for 42% (171 of 411) of the sample. Only 9%
      (37 of 411) of FSWs with acute STI reported an STI through self-report, which
      resulted in 33% (134 of 411) of FSWs who were considered underreporting their
      STI. STI underreporting was independently associated with younger age (adjusted
      odds ratio [aOR] 0.87, 95% confidence interval [CI] 0.76-0.99), a shorter
      duration of commercial sex (aOR 0.97, 95% CI 0.94-0.99), poorer knowledge of STI
      (aOR 0.81, 95% CI 0.70-0.94), and less sexual risks (aOR 0.52, 95% CI 0.41-0.66).
      CONCLUSIONS: Underreporting of STI was prevalent in FSWs, especially among women
      with perceived lower STI risks. The underreporting might be largely due to their
      perception of low risks for STI and unawareness of STI symptoms (including
      asymptomatic STIs). Future studies of FSWs should identify those new in
      commercial sex with lower STI awareness and perceived risks and encourage them to
      seek timely and appropriate testing and treatment.

PMID- 21194310
TI  - Assessment of insulin resistance and impaired glucose tolerance in lean women
      with polycystic ovary syndrome.
AB  - OBJECTIVE: To analyze insulin resistance (IR) and determine the need for a 2-hour
      oral glucose tolerance test (OGTT) for the identification of IR and impaired
      glucose tolerance (IGT) in lean nondiabetic women with polycystic ovary syndrome
      (PCOS). METHODS: This was a cross-sectional analysis of treatment-naive women
      with PCOS who enrolled in a university-based clinical trial. Nondiabetic women
      with PCOS based on the Eunice Kennedy Shriven National Institute of Child Health
      and Human Development (NICHD) definition, aged 18-43 years and weighing <=113 kg,
      were evaluated. Glucose and insulin levels were assessed at times 0, 30, 60, 90,
      and 120 minutes after a 75-g glucose load. Lean was defined as body mass index
      (BMI) <25 kg/m(2). Multiple linear regression was performed. RESULTS: A cohort of
      78 women was studied. The prevalence of IR was 0% among lean women vs. 21% among
      nonlean subjects based on fasting insulin I(0) and 40%-68% based on two different
      homeostatic model assessment (HOMA) cutoff points (p < 0.005). All women with IR
      had a BMI >= 28. Controlling for age and race, BMI explained over 57% of the
      variation in insulin fasting (I(o)), glucose fasting/Io (G(o)/I(o)), the
      qualitative insulin sensitivity check index (QUICKI), and HOMA and was a highly
      significant predictor of these outcomes (p < 0.0001). Only 1 of 31 (3%) of the
      lean PCOS women had IGT based on a 2-hour OGTT, and no lean subjects had IGT
      based on their fasting blood glucose. CONCLUSIONS: Diabetes mellitus, IGT, and IR
      are far less common in young lean women with PCOS compared with obese women with
      PCOS. These data imply that it is unnecessary to routinely perform either IR
      testing or 2-hour OGTT in lean women with PCOS; however, greater subject
      accumulation is needed to determine if OGTT is necessary in lean women with PCOS.
      BMI is highly predictive of both insulin and glucose levels in women with PCOS.

PMID- 21194311
TI  - Psychological impact of genetic counseling for hereditary nonpolyposis colorectal
      cancer: the role of cancer history, gender, age, and psychological distress.
AB  - AIMS: We prospectively examined the impact of an initial interdisciplinary
      genetic counseling (human geneticist, oncologist, and psycho-oncologist) on
      feelings of anxiety with a special focus on subgroups related to personal cancer
      history, gender, age, and education. RESULTS: At baseline, cancer-affected men
      revealed a significantly higher level of anxiety than unaffected men (p<0.05),
      whereas history of cancer did not play a role in women. Furthermore, a
      significant interaction between time, gender, and age was identified for change
      of anxiety. While women in general and men above 50 years revealed a significant
      reduction in anxiety, younger men did not show any change over time. A logistic
      regression indicated that clinical Hospital Anxiety and Depression Scale-A cases
      can be predicted by general distress (Brief Symptom Inventory) as well as by
      hereditary nonpolyposis colorectal cancer-related cognitions of intrusion and
      avoidance (impact of event scale) with a correct classification of 86%.
      CONCLUSIONS: Although initial hereditary nonpolyposis colorectal cancer
      counseling leads to an overall reduction of anxiety, differential effects of
      cancer history, gender, and age focus on subgroups of cancer-affected men, who
      may display unexpectedly high anxiety scores at baseline. Especially younger men
      do not seem to reduce this high anxiety level. Baseline anxiety was mainly
      determined by maladaptive situation-specific cognitions. Therefore, consulters
      should be more aware of anxiety-related cognitions in cancer-affected younger
      men.

PMID- 21194314
TI  - Concerns about the future of veterinary education.

PMID- 21194315
TI  - The veterinarian's role in animal cruelty cases.

PMID- 21194316
TI  - What is your diagnosis? Testicular torsion.

PMID- 21194317
TI  - What is your diagnosis? Osteochondrosis dissecans.

PMID- 21194318
TI  - Anesthesia case of the month. Atrial fibrillation.

PMID- 21194319
TI  - Pathology in practice. Bovine lymphoma.

PMID- 21194320
TI  - Pathology in practice. Penicilliosis.

PMID- 21194321
TI  - Designing studies that answer questions.

PMID- 21194322
TI  - Use of decision analysis to evaluate the delivery method of veterinary health
      care on dairy farms as measured by correction of left displaced abomasum.
AB  - OBJECTIVE: To use decision and sensitivity analysis to examine the delivery of
      health care on US dairy farms as measured by correction of left displaced
      abomasum (LDA). SAMPLE POPULATION: 5 journal articles evaluating outcomes from
      veterinarian- or herd personnel-delivered correction of LDA via laparotomy or a
      roll-and-toggle procedure. DESIGN: Economic analysis. PROCEDURES: A decision tree
      was constructed on the basis of published outcome data for correction of LDAs
      performed by veterinarians and herd personnel. Sensitivity of the model to
      changing input assumptions was evaluated via an indifference curve and tornado
      graph. RESULTS: Decision tree analysis revealed that correction of an LDA
      provided by herd personnel had an expected economic advantage of $76, compared
      with correction provided by a veterinarian. Sensitivity of this analysis to
      variations in inputs indicated that changes of 2 input levels would shift the
      advantage to veterinarian-provided correction: a reduction (from 0.74 to 0.62) in
      the probability of success for correction provided by herd personnel or an
      increase (from 0.78 to 0.87) in the probability of success for correction
      provided by a veterinarian. CONCLUSIONS AND CLINICAL RELEVANCE: In this model,
      LDA correction by herd personnel had a significant economic advantage, compared
      with veterinarian-provided correction. Continued absorption of traditional
      veterinary tasks by unlicensed herd personnel may threaten the veterinarian
      client-patient relationship (VCPR), which could have profound economic and
      regulatory impacts. Food animal veterinarians need to evaluate their business
      model to ensure they continue to provide relevant, sustainable services to their
      clients within the context of a valid VCPR.

PMID- 21194324
TI  - Sickness behaviors in response to unusual external events in healthy cats and
      cats with feline interstitial cystitis.
AB  - OBJECTIVE: To compare sickness behaviors (SB) in response to unusual external
      events (UEE) in healthy cats with those of cats with feline interstitial cystitis
      (FIC). DESIGN: Prospective observational study. ANIMALS: 12 healthy cats and 20
      donated cats with FIC. PROCEDURES: Cats were housed in a vivarium. Sickness
      behaviors referable to the gastrointestinal and urinary tracts, the skin, and
      behavior problems were recorded by a single observer for 77 weeks. Instances of
      UEE (eg, changes in caretakers, vivarium routine, and lack of interaction with
      the investigator) were identified during 11 of the 77 weeks. No instances of UEE
      were identified during the remaining 66 weeks, which were considered control
      weeks. RESULTS: An increase in age and exposure to UEE, but not disease status,
      significantly increased total number of SB when results were controlled for other
      factors. Evaluation of individual SB revealed a protective effect of food intake
      for healthy males. An increase in age conferred a small increase in relative risk
      (RR) for upper gastrointestinal tract signs (RR, 1.2) and avoidance behavior
      (1.7). Exposure to UEE significantly increased the RR for decreases in food
      intake (RR, 9.3) and for no eliminations in 24 hours (6.4). Exposure to UEE
      significantly increased the RR for defecation (RR, 9.8) and urination (1.6)
      outside the litter box. CONCLUSIONS AND CLINICAL RELEVANCE: SB, including some of
      the most commonly observed abnormalities in client-owned cats, were observed
      after exposure to UEE in both groups. Because healthy cats and cats with FIC were
      comparably affected by UEE, clinicians should consider the possibility of
      exposure to UEE in cats evaluated for these signs.

PMID- 21194325
TI  - Intraobserver and interobserver agreement for results of low-field magnetic
      resonance imaging in dogs with and without clinical signs of disk-associated
      wobbler syndrome.
AB  - OBJECTIVE: To determine interobserver and intraobserver agreement for results of
      low-field magnetic resonance imaging (MRI) in dogs with and without disk
      associated wobbler syndrome (DAWS). DESIGN: Validation study. ANIMALS: 21 dogs
      with and 23 dogs without clinical signs of DAWS. PROCEDURES: For each dog, MRI of
      the cervical vertebral column was performed. The MRI studies were presented in a
      randomized sequence to 4 board-certified radiologists blinded to clinical status.
      Observers assessed degree of disk degeneration, disk-associated and dorsal
      compression, alterations in intraspinal signal intensity (ISI), vertebral body
      abnormalities, and new bone formation and categorized each study as originating
      from a clinically affected or clinically normal dog. Interobserver agreement was
      calculated for 44 initial measurements for each observer. Intraobserver agreement
      was calculated for 11 replicate measurements for each observer. RESULTS: There
      was good interobserver agreement for ratings of disk degeneration and vertebral
      body abnormalities and moderate interobserver agreement for ratings of disk
      associated compression, dorsal compression, alterations in ISI, new bone
      formation, and suspected clinical status. There was very good intraobserver
      agreement for ratings of disk degeneration, disk-associated compression,
      alterations in ISI, vertebral body abnormalities, and suspected clinical status.
      There was good intraobserver agreement for ratings of dorsal compression and new
      bone formation. Two of 21 clinically affected dogs were erroneously categorized
      as clinically normal, and 4 of 23 clinically normal dogs were erroneously
      categorized as clinically affected. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggested that variability exists among observers with regard to results of MRI
      in dogs with DAWS and that MRI could lead to false-positive and false-negative
      assessments.

PMID- 21194326
TI  - Transcranial magnetic stimulation in Doberman Pinschers with clinically relevant
      and clinically irrelevant spinal cord compression on magnetic resonance imaging.
AB  - OBJECTIVE: To evaluate the use of transcranial magnetic stimulation for
      differentiating between clinically relevant and clinically irrelevant cervical
      spinal cord compression on magnetic resonance imaging (MRI). DESIGN: Validation
      study. ANIMALS: Clinically normal Doberman Pinschers without (n = 11) and with
      (6) spinal cord compression on MRI and 16 Doberman Pinschers with disk-associated
      wobbler syndrome (DAWS). PROCEDURES: After dogs were sedated, transcranial
      magnetic motor evoked potentials were recorded from the extensor carpi radialis
      muscle (ECRM) and cranial tibial muscle (CTM). Onset latencies and peak-to-peak
      amplitudes were measured. Magnetic resonance imaging was performed to identify
      spinal cord compression. RESULTS: There were significant differences in ECRM and
      CTM onset latencies between Doberman Pinschers with DAWS and each of the 2 groups
      of clinically normal dogs, but there were no significant differences in ECRM and
      CTM onset latencies between the 2 groups of clinically normal dogs. There were
      significant differences in CTM peak-to-peak amplitudes between Doberman Pinschers
      with DAWS and each of the 2 groups of clinically normal dogs, but there were no
      significant differences in ECRM peak-to-peak amplitudes among groups or in CTM
      peak-to-peak amplitudes between the 2 groups of clinically normal dogs. There was
      a significant correlation between severity of spinal cord compression and ECRM
      onset latency, CTM onset latency, and CTM peak-to-peak amplitude. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested that transcranial magnetic stimulation may
      be a useful diagnostic tool to differentiate between clinically relevant and
      clinically irrelevant spinal cord compression identified on MRI alone.

PMID- 21194327
TI  - Outcomes of cats undergoing surgical attenuation of congenital extrahepatic
      portosystemic shunts through cellophane banding: 9 cases (2000-2007).
AB  - OBJECTIVE: To evaluate the long-term prognosis of cats with a congenital
      extrahepatic portosystemic shunt (CEPSS) attenuated through gradual occlusion
      with cellophane banding (CB). DESIGN: Retrospective case series. ANIMALS: 9 cats
      with a CEPSS that was attenuated with CB. PROCEDURES: Medical records of cats
      surgically treated for CEPSS by means of CB from January 2000 through March 2007
      were reviewed. Extracted data included preoperative clinical signs, medications,
      diagnostic results including serum bile acids concentrations, surgical technique,
      intraoperative and postoperative complications, and long-term follow-up
      information. RESULTS: 2 cats that developed refractory seizures were euthanized
      within 3 days after the CB procedure. Seven of the 9 cats survived to 15 days
      after surgery. Four cats did not have any clinical signs of CEPSS at long-term
      follow up. At that time, 5 cats had a postprandial SBA concentration within
      reference limits and 1 cat had persistent ptyalism. One cat had biurate ammonium
      stones removed > 2 years after surgery. One cat was euthanized 105 days after
      surgery because of uncontrolled seizures. The 3-year survival rate was 66%.
      CONCLUSIONS AND CLINICAL RELEVANCE: Uncontrolled seizure activity was the most
      common cause of death after CB. Long-term outcome for cats with CEPSS was fair to
      good after the procedure. Cats with a CEPSS surviving the immediate postoperative
      period had a fair to good long-term outcome. Cellophane banding without
      intraoperative attenuation appears to be an acceptable technique for gradual
      occlusion of a CEPSS in cats. Cats should be monitored closely for development of
      neurologic disorders in the postoperative period.

PMID- 21194330
TI  - Evaluation of changes in haptoglobin and C-reactive protein concentrations caused
      by freezing of saliva and meat juice samples collected from healthy and diseased
      pigs.
AB  - OBJECTIVE: To evaluate changes in stability of haptoglobin and C-reactive protein
      (CRP) concentrations caused by freezing of saliva and meat juice samples.
      ANIMALS: 16 specific-pathogen-free pigs and 16 pigs with clinical signs of
      disease. PROCEDURES: Saliva and diaphragmatic muscle were collected immediately
      before and after slaughter, respectively. Haptoglobin and CRP concentrations of
      pooled samples were measured before storage (day 0) and after 7, 15, 30, 60, 120,
      210, and 365 days of storage at -20 degrees C and after repeated freezing-thawing
      cycles (up to 7 times). In a second experiment, addition of a protease-inhibitor
      cocktail to saliva and storage of saliva samples at -80 degrees C for up to 30
      days were assessed for effects on CRP concentrations. RESULTS: Haptoglobin
      concentrations in saliva did not change for up to 120 days in samples stored at 
      20 degrees C, but longer storage times and multiple freezing-thawing cycles
      increased haptoglobin concentrations. Salivary CRP concentrations decreased
      significantly after 7 days of storage at -20 degrees C, and addition of a
      protease-inhibitor cocktail did not improve CRP stability. Lower temperatures
      limited salivary CRP degradation. In meat juice, haptoglobin and CRP
      concentrations were stable at -20 degrees C up to 210 days. CONCLUSIONS AND
      CLINICAL RELEVANCE: Acute-phase protein measurements in saliva should be
      performed as soon as possible after sample collection. When this is not possible,
      storage temperature of -80 degrees C is recommended. Acute-phase protein
      concentrations appeared to be more stable in meat juice samples than in saliva
      samples. Saliva and meat juice could be used as alternatives to serum for
      haptoglobin and CRP analysis.

PMID- 21194328
TI  - Evaluation of the association between fecal excretion of Mycobacterium avium
      subsp paratuberculosis and detection in colostrum and on teat skin surfaces of
      dairy cows.
AB  - OBJECTIVE: To evaluate the association between fecal excretion of Mycobacterium
      avium subsp paratuberculosis (MAP) by dairy cows in the periparturient period and
      detection of MAP DNA in colostrum specimens and on teat skin surfaces. DESIGN:
      Cross-sectional study. ANIMALS: 112 Holstein cows. PROCEDURES: Fecal specimens
      were collected within 48 to 72 hours prior to parturition, and colostrum and teat
      swab specimens were collected immediately after parturition. Detection of MAP in
      fecal specimens was performed via microbial culture, and detection of MAP DNA in
      colostrum and teat swab specimens was achieved via a PCR assay targeting the
      genetic element ISMAP02. Logistic regression was used to model the relationship
      between MAP fecal shedding status and detection of MAP DNA in colostrum or teat
      swab specimens. Population attributable fractions for the proportion of colostrum
      and teat swab specimens containing MAP DNA were also calculated. RESULTS: The
      odds of detecting MAP DNA in colostrum or teat swab specimens in cows with MAP
      positive (vs negative) fecal specimens were 2.02 and 1.87 respectively.
      Population attributable fractions estimates suggested that withholding colostrum
      from MAP-positive cows could reduce the odds of exposing calves to MAP in
      colostrum by 18.2%. Not permitting natural suckling by calves could reduce the
      odds of exposing calves to MAP on the teat surfaces of MAP-positive cows by
      19.5%. CONCLUSIONS AND CLINICAL RELEVANCE: Results underscored the need for
      strict adherence to practices that limit contact of calves with adult cows from
      the time of birth and promote hygienic colostrum handling to avoid possible
      contamination with MAP during colostrum harvest, storage, or feeding.

PMID- 21194331
TI  - Effects of isoflurane anesthesia on cerebrovascular autoregulation in horses.
AB  - OBJECTIVE: To test a hypothesis predicting that isoflurane would interfere with
      cerebrovascular autoregulation in horses and to evaluate whether increased mean
      arterial blood pressure (MAP) would increase cerebral blood flow and intracranial
      pressure (ICP) during isoflurane anesthesia. ANIMALS: 6 healthy adult horses.
      PROCEDURES: Horses were anesthetized with isoflurane at a constant end-tidal
      concentration sufficient to maintain MAP at 60 mm Hg. The facial, carotid, and
      dorsal metatarsal arteries were catheterized for blood sample collection and
      pressure measurements. A sub-arachnoid transducer was used to measure ICP
      Fluorescent microspheres were injected through a left ventricular catheter during
      MAP conditions of 60 mm Hg, and blood samples were collected. This process was
      repeated with different-colored microspheres at the same isoflurane concentration
      during MAP conditions of 80 and 100 mm Hg achieved with IV administration of
      dobutamine. Central nervous system tissue samples were obtained after euthanasia
      to quantify fluorescence and calculate blood flow. RESULTS: Increased MAP did not
      increase ICP or blood flow in any of the brain tissues examined. However, values
      for blood flow were low for all tested brain regions except the pons and
      cerebellum. Spinal cord blood flow was significantly decreased at the highest
      MAP. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that healthy horses
      autoregulate blood flow in the CNS at moderate to deep planes of isoflurane
      anesthesia. Nonetheless, relatively low blood flows in the brain and spinal cord
      of anesthetized horses may increase risks for hypoperfusion and neurologic
      injury.

PMID- 21194332
TI  - Evaluation of the contribution of gyrA mutation and efflux pumps to
      fluoroquinolone and multidrug resistance in pathogenic Escherichia coli isolates
      from dogs and cats.
AB  - OBJECTIVE: To investigate the contribution of gyrA mutation and efflux pumps to
      fluoroquinolone resistance and multidrug resistance among Escherichia coli
      isolates from dogs and cats. SAMPLE POPULATION: 536 clinical isolates of E coli.
      PROCEDURES: Minimum inhibitory concentrations (MICs) were determined for
      enrofloxacin and 6 other drug classes by use of broth microdilution techniques.
      Real-time PCR assay was used to determine the mutation in gyrA; Phe-Arg-beta
      naphthylamide, an efflux pump inhibitor, was used to examine the contribution of
      efflux pump overexpression. RESULTS: The MIC for fluoroquinolones increased in a
      stepwise fashion and was lowest in the absence of mutations, higher with a single
      point mutation, and highest with 2 point mutations. Level of resistance in the
      latter category was high (8 times the breakpoint), but this was associated with
      expression of the AcrAB efflux pump. Inhibition of the efflux pump resulted in a
      reduction in the MIC to less than the susceptible breakpoint for isolates with an
      MIC <= 4 mg/L, regardless of the presence of a mutation. The greatest magnitude
      in MIC decrease (MIC was decreased by a factor of > 67 fold) was for isolates
      with a single mutation but the greatest absolute decrease in MIC (124 mg/L) was
      for isolates with 2 mutations. Inhibition of the AcrAB efflux pump in isolates
      characterized by multidrug resistance decreased the MIC of drugs structurally
      unrelated to fluoroquinolone. CONCLUSIONS AND CLINICAL RELEVANCE: Fluoroquinolone
      resistance in E coli appeared to be a stepwise phenomenon, with MIC increasing as
      the number of point mutations in gyrA increased, but high-level resistance and
      multidrug resistance associated with fluoroquinolone resistance reflected
      overexpression of the AcrAB efflux pump.

PMID- 21194333
TI  - Histopathologic features of distal tarsal joint cartilage and subchondral bone in
      ridden and pasture-exercised horses.
AB  - OBJECTIVE: To determine whether histopathologic characteristics of the
      osteochondral units of equine distal tarsal joints were associated with exercise
      history in horses without lameness. SAMPLE POPULATION: 30 cadaver tarsi from
      horses without lameness and with known exercise history were separated into 3
      groups: nonridden, pasture exercise (group P); low-intensity, ridden exercise
      (group L); and high-intensity, elite competition exercise (group E). PROCEDURES:
      Standardized sites from the centrodistal and tarsometatarsal joints under went
      histologic preparation. A grading system was adapted to describe location, depth,
      and shape of lesions; cellular arrangement; organization at cartilage and
      subchondral bone (SCB) junctions; and organization of SCB. A high score signified
      a more severe pathological change than a low score. Exercise groups were compared
      by calculation of Spearman rank correlations. RESULTS: In the centrodistal joint,
      lesions were present in groups L and E but only medially. Cellular arrangement
      scores were higher at the dorsomedial location in group P than in groups L and E.
      Groups L and E had higher scores than group P for the organization of the
      cartilage, SCB junctions, and SCB, with higher scores at the dorsomedial
      location. In the tarsometatarsal joint, lesions were evident across the whole
      joint surface, with more severe lesions located laterally in all 3 groups.
      Overall, group E had higher scores for cellular arrangement and SCB organization
      than groups P and L. CONCLUSIONS AND CLINICAL RELEVANCE: Ridden exercise may
      increase the risk of osteochondral lesions at distal tarsal sites predisposed to
      osteoarthritis relative to the risk with nonridden exercise.

PMID- 21194334
TI  - Hyaluronic acid and chondrogenesis of murine bone marrow mesenchymal stem cells
      in chitosan sponges.
AB  - OBJECTIVE: To establish the dose-dependent effects of high-molecular-weight
      hyaluronic acid (HA) supplementation on chondrogenesis by mesenchymal stem cells
      (MSCs) cultured on chitosan sponges and to determine the extent to which MSC
      matrix production (chondrogenesis) can be influenced by incorporation of high
      molecular-weight HA into chitosan scaffolds. SAMPLE POPULATION: Murine MSCs
      derived from a multipotent bone marrow stromal precursor. PROCEDURES: MSCs were
      seeded on chitosan and chitosan-HA scaffolds in chondrogenic medium with various
      HA concentrations. Scanning electron microscopy, fluorescence microscopy
      (viability assay), and DNA quantification were used to assess cell attachment,
      distribution, and viability 48 hours after seeding. Constructs were cultured for
      3 weeks prior to evaluation of cell distribution and chondrogenic differentiation
      via histologic evaluation and quantification of DNA, glycosaminoglycan, and
      collagen II. RESULTS: 48 hours after MSC seeding, cell viability and DNA content
      were similar among groups. Three weeks after seeding, HA supplementation of the
      culture medium improved matrix production in a dose-dependent manner, as
      indicated by matrix glycosaminoglycan and collagen II concentrations. The
      scaffold composition, however, had no significant effect on matrix production.
      CONCLUSIONS AND CLINICAL RELEVANCE: High-molecular-weight HA supplementation in
      culture medium had a dose-dependent effect on matrix production and thus
      chondrogenic differentiation of MSCs cultured on chitosan sponges. The addition
      of HA in the surrounding fluid during chondrogenesis should improve cartilage
      production and may be useful for producing engineered cartilage tissues.

PMID- 21194335
TI  - Modulation of cytokine-induced prostaglandin E2 production in cultures of
      articular chondrocytes obtained from carpal joints of camels (Camelus
      dromedarius).
AB  - OBJECTIVE: To determine whether camel articular chondrocytes can be maintained in
      tissue culture without phenotype loss and whether the response to cytokine
      stimulation can be modulated. SAMPLE POPULATION: Cartilage from 4 carpal joints
      of healthy adult dromedary camels (Camelus dromedarius). PROCEDURES: Chondrocytes
      were evaluated for type II collagen and aggrecan production They were incubated
      with control media or with 2 test mixtures (alone and then in combination) that
      have anti-inflammatory activity (avocado-soybean unsaponifiables, glucosamine,
      and chondroitin sulfate [ie, ASU + GLU + CS] and pentosan polysulfate and N
      acetyl glucosamine [ie, PPS + NG]). Cells were then stimulated with interleukin
      1beta and tumor necrosis factor-alpha to determine prostaglandin (PG) E2
      production and nuclear factor (NF)-kappaB activation. RESULTS: Chondrocytes
      proliferated in media used for propagating equine chondrocytes; they produced
      type II collagen and aggrecan. Cytokine stimulation induced PGE2 production and
      translocation of NF-kappaB. Incubation with each test mixture significantly
      inhibited PGE2 production. The combination of ASU + GLU + CS and PPS + NG
      significantly potentiated PGE2 inhibition and disrupted NF-kappaB translocation,
      compared with effects for either mixture alone. CONCLUSIONS AND CLINICAL
      RELEVANCE: Chondrocytes proliferated without loss of the cartilage phenotype.
      Responses to cytokines were significantly inhibited by the mixtures of ASU + GLU
      + CS and PPS + NG, which indicated that this response can be modulated. This
      culture technique can be used to study the functional properties of camel
      chondrocytes and identify agents that may potentially be used to treat and manage
      joint inflammation.

PMID- 21194336
TI  - Evaluation of pulsatile plasma concentrations of growth hormone in healthy dogs
      and dogs with dilated cardiomyopathy.
AB  - OBJECTIVE: To evaluate plasma concentrations of growth hormone (GH) and insulin
      like growth factor I (IGF-I) in healthy dogs and large-breed dogs with dilated
      cardiomyopathy (DCM). ANIMALS: 8 dogs with DCM and 8 healthy control dogs of
      comparable age and body weight. PROCEDURES: Blood samples for determination of
      the pulsatile plasma GH profile were collected from all dogs at 10-minute
      intervals between 8:00 am and 8:00 pm. Plasma IGF-I concentration was determined
      in the blood sample collected at 8:00 am. RESULTS: No significant differences in
      plasma IGF-I concentrations, basal plasma GH concentration, GH pulse frequency,
      area under the curve above the zero line and above the baseline for GH, and GH
      pulse amplitude were found between dogs with DCM and control dogs. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results did not provide evidence for an association
      between DCM in dogs and a reduction in plasma concentrations of GH or IGF-I.
      Therefore, reported positive effects of GH administration are most likely
      attributable to local effects in the heart.

PMID- 21194337
TI  - Influence of blood collection technique on platelet function and coagulation
      variables in dogs.
AB  - OBJECTIVE: To investigate the influence of diameter of the catheter and blood
      collection technique on platelet function and variables reflecting secondary
      hemostasis, physiologic anticoagulation, and fibrinolysis in dogs. ANIMALS: 6
      healthy Beagles. PROCEDURES: Blood samples were collected with 20- and 18-gauge
      venous catheters immediately after catheters were inserted in a peripheral vein,
      through a 14-gauge central venous catheter that had been placed via the Seldinger
      technique in a jugular vein < 30 minutes before sample collection, and through a
      13-gauge central venous catheter placed via a catheter-through-the-needle
      technique < 30 minutes before sample collection (techniques 1 to 4,
      respectively). Platelet function was assessed in hirudin-anticoagulated whole
      blood via an impedance-based aggregometer with collagen (0.8, 0.4, 0.2, 0.1, and
      0.05 MUg/mL) as an inductor. Kaolin-activated thromboelastography variables were
      determined in citrated whole blood. Prothrombin time, activated partial
      thromboplastin time, fibrinogen and fibrin D-dimer concentrations, and activity
      of factor VIII, antithrombin, protein C, and protein S were assessed
      automatically in citrated plasma. RESULTS: At 0.05 MUg of collagen/mL, the
      highest median rate of aggregation was observed for collection techniques 2 and 3
      with 4.3 (range, 2.5 to 6.5) and 3.7 (range, 2.8 to 8.3) aggregation units/min;
      however, these values were not significantly different from values for the other
      collection techniques. Generally, sample collection technique did not have a
      significant impact on results of coagulation variables investigated. CONCLUSIONS
      AND CLINICAL RELEVANCE: Various blood collection techniques can be used to obtain
      samples for coagulation testing.

PMID- 21194339
TI  - Adhesion phenotypes of pigs of Chinese and Western breeds and a White Duroc
      Erhualian crossbreed with regard to susceptibility to enterotoxigenic Escherichia
      coli with fimbrial adhesins K99, 987P, and F41.
AB  - OBJECTIVE: To investigate adhesion phenotypes of pigs of Chinese and Western
      breeds and a specific crossbreed with regard to enterotoxigenic Escherichia coli
      (ETEC) with fimbrial adhesins K99 (F5), 987P (F6), and F41 (F7). ANIMALS:
      Purebred 6- to 8-week-old pigs of 3 Western breeds introduced into China (n =
      144) and 12 Chinese breeds (148) and 1,330 adult White Duroc-Erhualian crossbred
      pigs. PROCEDURES: Brush border preparations were prepared from jejunal specimens
      collected from each pig following euthanasia. Each preparation was incubated with
      ETEC strains that had fimbrial adhesins K99, 987R or F41; an ETEC K88(-) strain
      was used as a negative control sample. The mean number of brush border-bound
      bacteria in aliquots of the bacteria-brush border suspensions (determined via
      phase-contrast microscopy) was used to determine each pig's adhesion phenotype
      for ETEC K99, 987R and F41 strains; the phenotype was classified as adhesive
      (susceptible) if >= 10% of examined brush borders bound > 2 bacteria. RESULTS:
      Most purebred and crossbred pigs had nonadhesive phenotypes with regard to ETEC
      K99 and 987P strains. For the F41 strain, 34.9% and 65.1% of all purebred pigs
      had adhesive and nonadhesive phenotypes, respectively; among crossbred pigs,
      these values were 39.2% and 60.8%, respectively. The percentage of pigs with the
      F41 adhesive phenotype was higher among Western breeds than it was among Chinese
      breeds (38.9% vs 31.1%). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested
      that the ETEC F41 strain, but not the K99 or 987P strain, might be a cause of
      diarrhea in 6- to 8-week-old pigs in China.

PMID- 21194338
TI  - Effects of location for collection of air samples on a farm and time of day of
      sample collection on airborne concentrations of virulent Rhodococcus equi at two
      horse breeding farms.
AB  - OBJECTIVE: To determine whether airborne concentrations of virulent Rhodococcus
      equi at 2 horse breeding farms varied on the basis of location, time of day, and
      month. SAMPLE POPULATION: 2 farms in central Kentucky with recurrent R equi
      induced pneumonia in foals. PROCEDURES: From February through July 2008, air
      samples were collected hourly for a 24-hour period each month from stalls and
      paddocks used to house mares and their foals. Concentrations of airborne virulent
      R equi were determined via a modified colony immunoblot technique. Differences
      were compared by use of zero-inflated negative binomial methods to determine
      effects of location, time, and month. RESULTS: Whether mares and foals were
      housed predominantly in stalls or paddocks significantly affected results for
      location of sample collection (stall vs paddock) by increasing airborne
      concentrations of virulent R equi at the site where horses were predominantly
      housed. Airborne concentrations of virulent R equi were significantly higher from
      6:00 pm through 11:59 pm than for the period from midnight through 5:59 am.
      Airborne concentrations of virulent R equi did not differ significantly between
      farms or among months. CONCLUSIONS AND CLINICAL RELEVANCE: Airborne
      concentrations of virulent R equi were significantly increased when horses were
      predominantly housed at the site for collection of air samples (ie, higher in
      stalls when horses were predominantly housed in stalls and higher in paddocks
      when horses were predominantly housed in paddocks). Concentrations of virulent R
      equi among air samples collected between the hours of 6:00 am and midnight
      appeared similar.

PMID- 21194340
TI  - Evaluation of orally administered famciclovir in cats experimentally infected
      with feline herpesvirus type-1.
AB  - OBJECTIVE: To evaluate orally administered famciclovir for treatment of cats with
      experimentally induced disease attributable to feline herpesvirus type-1 (FHV-1).
      ANIMALS: 16 nonvaccinated specific-pathogen-free cats. PROCEDURES: Cats were
      treated orally with famciclovir (90 mg/kg; n = 10) or a similar volume of lactose
      (400 mg; 6) 3 times/d for 21 days. Cats were inoculated with FHV-1 and
      administered the first treatment dose on day 0. Disease score; weight; results of
      urinalysis, serum biochemical analysis, and CBC; histologic conjunctivitis score;
      herpetic DNA shedding; goblet cell density; anti-FHV-1 antibody concentration;
      and plasma penciclovir concentration were measured. RESULTS: On days 4 to 18
      following inoculation, disease scores were lower in famciclovir-treated cats than
      in lactose-treated cats. Lactose-treated cats decreased in weight during the
      first 7 days after inoculation, but famciclovir-treated cats increased in weight
      throughout the study. Percentage change in weight was greater in famciclovir
      treated cats on days 7 and 14 than in lactose-treated cats. Serum globulin
      concentration was lower on days 3 through 9, conjunctivitis histologic score was
      lower on day 14, herpetic DNA was shed less frequently throughout the study,
      goblet cell density was greater on day 21, and circulating anti-FHV-1 antibody
      concentration at study end was lower in famciclovir-treated cats, compared with
      these measurements in lactose-treated cats. Approximate peak plasma penciclovir
      concentration was 2.0 MUg/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Famciclovir
      administration improved outcomes for systemic, ophthalmic, clinicopathologic,
      virologic, and histologic variables in cats experimentally infected with FHV-1.
      Adjunctive topical mucinomimetic and antimicrobial treatments may also be
      necessary.

PMID- 21194341
TI  - Genotypic relatedness and phenotypic characterization of Staphylococcus
      schleiferi subspecies in clinical samples from dogs.
AB  - OBJECTIVE: To assess the degree of biological similarity (on the basis of
      genotype determined via pulsed-field gel electrophoresis [PFGE]) between isolates
      of 2 Staphylococcus schleiferi subspecies (S schleiferi subsp coagulans and S
      schleiferi subsp schleiferi) in clinical samples obtained from dogs. SAMPLE
      POPULATION: 161 S schleiferi isolates from 160 canine patients. PROCEDURES: A
      commercial microbiology identification system was used to identify each isolate
      as S schleiferi. Isolates underwent slide and tube coagulase testing and
      antimicrobial susceptibility testing. A mecA PCR assay and a latex agglutination
      test for penicillin-binding protein 2a (PBP2a) were also performed on each
      isolate. Clonal clusters with a similarity cutoff value of 80% were identified
      via PFGE. RESULTS: Of the 161 isolates, 61 (38%), 79 (49%), and 21 (13%) were
      obtained from cutaneous sites, ears, and other sites, respectively; 110 (68%)
      were coagulase negative, and 51 (32%) were coagulase positive. Among the
      coagulase-negative and coagulase-positive isolates, 65% (71/110) and 39% (20/51)
      were oxacillin resistant, respectively. All oxacillin-resistant isolates yielded
      positive results via mecA PCR assay and PBP2a latex agglutination testing. Via
      PFGE, 15 major clusters and 108 individual pulsed-field profiles were identified.
      Oxacillin-resistant and oxacillin-susceptible isolates clustered separately.
      Clonal clusters were heterogeneous and contained representatives of both
      subspecies. CONCLUSIONS AND CLINICAL RELEVANCE: Coagulase-positive and coagulase
      negative isolates were not genotypically distinct and may represent a single S
      schleiferi sp with variable coagulase production, rather than 2 biologically
      distinct subspecies. Further studies are needed to characterize clinical or
      epidemiological differences associated with infections with coagulase-positive
      and coagulase-negative S schleiferi in dogs.

PMID- 21194342
TI  - Evaluation of an acute focal epidural mass model to characterize the intracranial
      pressure-volume relationship in healthy Beagles.
AB  - OBJECTIVE: To characterize the intracranial pressure-volume relationship (ICPVR)
      in dogs by use of an acute frontal-parietal mass lesion model. ANIMALS: 7 healthy
      adult female Beagles. PROCEDURES: Dogs were anesthetized with isoflurane to
      achieve a surgical plane of anesthesia. A fiberoptic intracranial pressure (ICP)
      monitor was inserted to a depth of 1 cm in the parenchyma of the right frontal
      parietal region of the brain. A Foley balloon-tipped catheter was placed in the
      epidural space of the left frontal-parietal area through a separate 1-cm burr
      hole. Baseline measurements were obtained with the balloon deflated. The balloon
      was then inflated incrementally with 0.5 mL of 0.9% NaCl solution every 10
      minutes until ICP exceeded mean arterial blood pressure. Nonlinear regression
      analysis with 2-factor and 3-factor exponential equations was used to
      characterize the ICPVR. RESULTS: The mean baseline ICP was 11 mm Hg, with a 95%
      confidence interval of 2 to 20 mm Hg. The ICPVR was well characterized by 2
      factor or 3-factor exponential equations for all dogs (R2 > 0.93). Balloon
      volumes of > 1. 2 mL were associated with ICP > 20 mm Hg. CONCLUSIONS AND
      CLINICAL RELEVANCE: Characterization of the ICPVR may provide clinically useful
      information regarding the safety of obtaining CSF from the atlanto-occipital
      space or implantation of brachytherapy catheters and for determining the need for
      decompressive craniectomy in dogs with acute intracranial disease. High ICP
      should be suspected in dogs that have an acute frontal-parietal mass lesion
      estimated to exceed 2% of the brain volume.

PMID- 21194343
TI  - Evaluation of minimally invasive excisional brain biopsy and intracranial
      brachytherapy catheter placement in dogs.
AB  - OBJECTIVE: To evaluate a technique for minimally invasive excisional brain biopsy
      and intracranial brachytherapy catheter placement in dogs. ANIMALS: 5 healthy
      adult female dogs. PROCEDURES: Computed tomographic guidance was used to plan a
      biopsy trajectory to a selected area of brain with reference to a localizer grid.
      The procedure was performed through a 1-cm skin incision and 6-mm burr hole by
      use of a 9-gauge biopsy device. Five cylindrical samples (3 to 4 mm in diameter
      and 7 to 12 mm in length) were removed over 5 cycles of the vacuum-assisted
      tissue excision system, leaving approximately a 2-cm3 resection cavity. A balloon
      tipped intracranial brachytherapy catheter was placed through the burr hole into
      the resection cavity, expanded with saline (0.9% NaCl) solution, and explanted 7
      days later. RESULTS: 4 of 5 dogs survived the procedure. The fifth died because
      of iatrogenic brain damage. Neurologic deficits were unilateral and focal. Twenty
      four hours after surgery, all surviving dogs were ambulatory, 2 dogs exhibited
      ipsiversive circling, 4 had contralateral proprioceptive deficits, 3 had
      contralateral menace response deficits, 2 had a reduced contralateral response to
      noxious nasal stimulation, and 1 had dull mentation with intermittent horizontal
      nystagmus and ventrolateral strabismus. Neurologic status improved throughout the
      study period. Histologic quality of biopsy specimens was excellent. CONCLUSIONS
      AND CLINICAL RELEVANCE: This technique enabled histologic diagnosis from high
      quality biopsy specimens obtained through a minimally invasive technique and has
      potential applications for multimodal treatment of deep brain tumors in dogs.

PMID- 21194344
TI  - Pharmacokinetics and bioavailability of cefquinome in healthy ducks.
AB  - OBJECTIVE: To determine pharmacokinetics and bioavailability of cefquinome
      administered IV, IM, or PO to healthy ducks. ANIMALS: Thirty-six 2-month-old
      Muscovy ducks. PROCEDURES: Ducks were randomly assigned to 3 groups of 12 birds
      each for a single IV, IM, or PO administration at a dose of 5 mg/kg. Blood
      samples were collected before and at various intervals after each administration.
      Cefquinome concentration was determined by use of high-performance liquid
      chromatography at 268 nm with a UV detector, and pharmacokinetics were analyzed.
      RESULTS: The disposition of cefquinome following IV or IM administration was best
      described by a 2-compartment model. After IV administration, mean +/- SD
      elimination halflife was 1.57 +/- 0.06 hours, clearance value was 0.22 +/- 0.02
      L/kg.h, and apparent volume of distribution at steady state was 0.41 +/- 0.04
      L/kg. After IM administration, elimination half-life was 1.79 +/- 0.13 hours,
      peak concentration time was 0.38 +/- 0.06 hours, peak drug concentration was 9.38
      +/- 1.61 MUg/mL, and absolute mean +/- SD bioavailability was 93.28 +/- 13.89%.
      No cefquinome was detected in plasma after PO administration. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results indicated that cefquinome was absorbed quickly and
      had excellent bioavailability after IM administration, but absorption after PO
      administration was poor.

PMID- 21194345
TI  - Evaluation of equine peripheral blood apheresis product, bone marrow, and adipose
      tissue as sources of mesenchymal stem cells and their differentation potential.
AB  - OBJECTIVE: To evaluate effects of apheresis on mesenchymal stem cells (MSCs) and
      compare those MSCs with MSCs obtained from adipose tissue or bone marrow (BM).
      SAMPLE POPULATION: Samples obtained from 6 adult horses. PROCEDURES: Samples of
      blood from a peripheral vein, adipose tissue, and BM aspirate were obtained from
      each horse. Samples were processed via apheresis of blood and techniques reported
      elsewhere for adipose tissue and BM. Cultures were maintained until adherence and
      subsequently were subjected to differentiation protocols to evaluate adipogenic,
      osteoblastogenic, and chondrogenic potential. RESULTS: Apheresis product had a
      significantly higher mononuclear percentage, higher platelet count, and lower RBC
      count, compared with values for peripheral blood. No cell adherence to the tissue
      culture plates was detected for the apheresis product. Adherence was detected for
      6 of 6 adipose-derived and 4 of 6 BM-derived samples. Variations in efficiency
      were detected for differentiation of adipose- and BM-derived cells into
      adipocytes, chondrocytes, and osteoblasts. CONCLUSIONS AND CLINICAL RELEVANCE:
      Apheresis was able to concentrate mononuclear cells and reduce RBC contamination.
      However, the apheresis product was unable to adhere to the tissue culture plates.
      In matched horses, adipose- and BM-derived MSCs were capable of producing lipids,
      glycosaminoglycan, and mineral. The BM was vastly superior to adipose tissue as a
      source of MSCs with osteoblastogenic potential in matched horses. Additional
      studies will be necessary to optimize apheresis techniques for horses before
      peripheral blood can be considered a suitable source for multipotential cells for
      use in cell-based treatments.

PMID- 21194346
TI  - Assessment of IgE response and cytokine gene expression in pulmonary efferent
      lymph collected after ovalbumin inhalation during experimental infection of
      calves with bovine respiratory syncytial virus.
AB  - OBJECTIVE: To assess IgE response and cytokine gene expressions in pulmonary
      lymph collected from bovine respiratory syncytial virus (BRSV)-infected calves
      after ovalbumin inhalation. ANIMALS: Thirteen 7- to 8-week-old calves.
      PROCEDURES: The efferent lymphatic duct of the caudal mediastinal lymph node of
      each calf was cannulated 3 or 4 days before experiment commencement. Calves were
      inoculated (day 0) with BRSV (n = 7) or BRSV-free tissue culture medium (mock
      exposure; 6) via aerosolization and exposed to aerosolized ovalbumin on days 1
      through 6 and day 15. An efferent lymph sample was collected daily from each calf
      on days -1 through 16; CD4+ and CD8+ T lymphocyte subsets in lymph samples were
      enumerated with a fluorescence-activated cell scanner. Expressions of several
      cytokines by efferent lymphocytes and lymph ovalbumin-specific IgE concentration
      were measured. Each calf was euthanized on day 16 and then necropsied for
      evaluation of lungs. RESULTS: Mean fold increase in ovalbumin-specific IgE
      concentration was greater in BRSV-infected calves than in mock-infected calves.
      At various time points from days 4 through 10, percentages of T lymphocyte
      subsets and CD4+:CD8+ T lymphocyte ratios differed between BRSV-infected calves
      and day -1 values or from values in mock-infected calves. On days 3 through 5, IL
      4 and IL-13 gene expressions in BRSV-infected calves were increased, compared
      with expressions in mock-infected calves. Lung lesions were consistent with
      antigen exposure. CONCLUSIONS AND CLINICAL RELEVANCE: In response to the
      inhalation of aerosolized ovalbumin, BRSV infection in calves appeared to
      facilitate induction of a T helper 2 cell response and ovalbumin-specific IgE
      production.

PMID- 21194347
TI  - Evaluation of the effects of thiopental, propofol, and etomidate on glomerular
      filtration rate measured by the use of dynamic computed tomography in dogs.
AB  - OBJECTIVE: To evaluate the effects of thiopental, propofol, and etomidate on
      glomerular filtration rate (GFR) measured by the use of dynamic computed
      tomography in dogs. ANIMALS: 17 healthy Beagles. PROCEDURES: Dogs were randomly
      assigned to receive 2 mg of etomidate/kg (n = 5), 6 mg of propofol/kg (7), or 15
      mg of thiopental/kg (5) during induction of anesthesia; anesthesia was
      subsequently maintained by isoflurane evaporated in 100% oxygen. A 1 mL/kg dosage
      of a 300 mg/mL solution of iohexol was administered at a rate of 3 mL/s during
      GFR measurement. Regions of interest of the right kidney were manually drawn to
      exclude vessels and fatty tissues and highlight the abdominal portion of the
      aorta. Iohexol clearance per unit volume of the kidney was calculated by use of
      Patlak plot analysis. RESULTS: Mean +/- SD weight-adjusted GFR of the right
      kidney after induction of anesthesia with thiopental, propofol, and etomidate was
      2.04 +/- 0.36 mL/min/kg, 2.06 +/- 0.29 mL/min/kg, and 2.14 +/- 0.43 mL/min/kg,
      respectively. However, no significant differences in weight-adjusted GFR were
      detected among the treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      obtained for the measurement of GFR in anesthetized dogs after anesthetic
      induction with etomidate, propofol, or thiopental and maintenance with isoflurane
      did not differ significantly. Therefore, etomidate, propofol, or thiopental can
      be used in anesthesia-induction protocols that involve the use of isoflurane for
      maintenance of anesthesia without adversely affecting GFR measurements obtained
      by the use of dynamic computed tomography in dogs.

PMID- 21194348
TI  - Preclinical, clinical, and over-the-counter postmarketing experience with a new
      vaginal cup: menstrual collection.
AB  - BACKGROUND: Menstrual cups have been available for decades, but their use is
      limited by bulky design and the need for multiple sizes. The Softcup(r) (Instead,
      Inc., San Diego, CA) is a simple single-size disposable over-the-counter (OTC)
      menstrual cup that compresses to tampon shape to facilitate insertion and can be
      worn during coitus. This report describes preclinical evaluation, clinical
      testing, and postmarketing monitoring of the Softcup. METHODS: Preclinical
      testing complied with U.S. Food and Drug Administration (FDA) guidelines and used
      standard United States Pharmacopoeia methodologies for assessment of potential
      toxicity. Clinical testing enrolled 406 women in seven U.S. centers. A detailed
      written questionnaire assessed safety, acceptability, and effectiveness for
      menstrual collection. Study safety parameters included pelvic examinations, Pap
      smears, colposcopy, urinalysis, vaginal pH, wet mounts, gram stain, and vaginal
      microflora cultures. Postmarketing surveillance of over 100 million Softcups has
      been conducted by the manufacturer and by the FDA Medwatch system. RESULTS: No
      toxicity or mutagenicity was observed in preclinical evaluations. In clinical
      testing, after three cycles of cup use, 37% of subjects rated the cup as better
      than, 29% as worse than, and 34% as equal to pads or tampons. The cup was
      preferred for comfort, dryness, and less odor. Cups received lower ratings for
      disposal and convenience. Eighty-one percent of enrolled women were able to
      insert and remove their first cup using only written instructions. Use
      difficulties resulting in study discontinuations included cramping (1%), leakage
      (1%), and improper fit (3%). No safety parameters were adversely affected. No
      significant health risks were reported during postmarketing surveillance.
      CONCLUSIONS: These results demonstrate that a single-size vaginal device has no
      significant health risks and is acceptable to many women without the need for
      fitting or other medical services.

PMID- 21194349
TI  - Highly pathogenic (H5N1) avian influenza induces an inflammatory T helper type 1
      cytokine response in the chicken.
AB  - To better understand the immune response to highly pathogenic avian influenza
      virus, we compared expression of cytokines in chickens infected with avian
      influenza virus (A/Vietnam/1203/04) to that in uninfected chickens. Gene
      expression analyses revealed that influenza disseminated to multiple organs where
      immune responses could be identified. Among those cytokines influenced by
      influenza infection were the T helper type (Th)1-associated cytokines interleukin
      (IL)12 and interferon gamma. In addition, a corresponding downregulation of the
      intracytoplasmic factor GATA3 was identified, whereas the Th2 cytokines IL4 and
      IL10 did not appear to be impacted by the infection. The inflammatory cytokine
      IL6 also appeared to be highly upregulated along with type 1 and type 3
      interferon. Together, these data indicate that a strong inflammatory and Th1
      response occurs after highly pathogenic avian influenza infection in the chicken
      that has implications for strategies that target the immune system for improving
      resistance to avian influenza.

PMID- 21194350
TI  - Both maximal expression of selenoproteins and selenoprotein deficiency can
      promote development of type 2 diabetes-like phenotype in mice.
AB  - Selenium (Se) is an essential trace element in mammals that has been shown to
      exert its function through selenoproteins. Whereas optimal levels of Se in the
      diet have important health benefits, a recent clinical trial has suggested that
      supplemental intake of Se above the adequate level potentially may raise the risk
      of type 2 diabetes mellitus. However, the molecular mechanisms for the effect of
      dietary Se on the development of this disease are not understood. In the present
      study, we examined the contribution of selenoproteins to increased risk of
      developing diabetes using animal models. C57BL/6J mice (n=6-7 per group) were fed
      either Se-deficient Torula yeast-based diet or diets supplemented with 0.1 and
      0.4 parts per million Se. Our data show that mice maintained on an Se
      supplemented diet develop hyperinsulinemia and have decreased insulin
      sensitivity. These effects are accompanied by elevated expression of a selective
      group of selenoproteins. We also observed that reduced synthesis of these
      selenoproteins caused by overexpression of an i(6)A(-) mutant selenocysteine tRNA
      promotes glucose intolerance and leads to a diabetes-like phenotype. These
      findings indicate that both high expression of selenoproteins and selenoprotein
      deficiency may dysregulate glucose homeostasis and suggest a role for
      selenoproteins in development of diabetes.

PMID- 21194352
TI  - Regulation of heart function by endogenous gaseous mediators-crosstalk between
      nitric oxide and hydrogen sulfide.
AB  - Both nitric oxide (NO) and hydrogen sulfide (H(2)S) are two important gaseous
      mediators regulating heart function. The present study examined the interaction
      between these two biological gases and its role in the heart. We found that l
      arginine, a substrate of NO synthase, decreased the amplitudes of myocyte
      contraction and electrically induced calcium transients. Sodium hydrogen sulfide
      (an H(2)S donor), which alone had minor effect, reversed the negative inotropic
      effects of l-arginine. The effect of l-arginine + sodium hydrogen sulfide was
      abolished by three thiols (l-cysteine, N-acetyl-cysteine, and glutathione),
      suggesting that the effect of H(2)S + NO is thiol sensitive. The stimulatory
      effect on heart contractility was also induced by GYY4137, a slow-releasing H(2)S
      donor, when used together with sodium nitroprusside, an NO-releasing donor. More
      importantly, enzymatic generation of H(2)S from recombinant cystathionine-gamma
      lyase protein also interacted with endogenous NO generated from l-arginine to
      stimulate heart contraction. In summary, our data suggest that endogenous NO may
      interact with H(2)S to produce a new biological mediator that produces positive
      inotropic effect. The crosstalk between H(2)S and NO also suggests an intriguing
      potential for the endogenous formation of a thiol-sensitive molecule, which may
      be of physiological significance in the heart.

PMID- 21194354
TI  - Oxidative stress in schizophrenia: pathogenetic and therapeutic implications.
AB  - Over a century, a wide-ranging variety of pathophysiological models and causal
      hypotheses have been conceptualized for schizophrenia. One among these is the
      role for free radical-mediated pathology in schizophrenia, indicating impaired
      antioxidant defense system (AODS) and presence of oxidative stress in patients
      with schizophrenia. For the past two decades, the whole investigative domain of
      AODS and oxidative stress has broadened to include the wider AODS components,
      direct central nervous system assays of AODS, chemical imaging studies,
      proteomics, genetics of AODS, and, of importance to sufferers of schizophrenia,
      antioxidant therapeutics. These are some of the perspectives that are reviewed by
      several articles in this Forum. Overall, there has been growing recognition of
      the importance of oxidative stress in the pathophysiology of schizophrenia and in
      treatment-related side effects. The totality of the evidence from biochemistry,
      metabolomics, proteomics, genetics, and in vivo brain imaging points to the
      presence of multifarious abnormalities in the AODS and redox signaling in
      schizophrenia.

PMID- 21194353
TI  - Regulation of endothelial function by mitochondrial reactive oxygen species.
AB  - Mitochondria are well known for their central roles in ATP production, calcium
      homeostasis, and heme and steroid biosynthesis. However, mitochondrial reactive
      oxygen species (ROS), including superoxide and hydrogen peroxide, once thought to
      be toxic byproducts of mitochondrial physiologic activities, have recently been
      recognized as important cell-signaling molecules in the vascular endothelium,
      where their production, conversion, and destruction are highly regulated.
      Mitochondrial reactive oxygen species appear to regulate important vascular
      homeostatic functions under basal conditions in a variety of vascular beds,
      where, in particular, they contribute to endothelium-dependent vasodilation. On
      exposure to cardiovascular risk factors, endothelial mitochondria produce
      excessive ROS in concert with other cellular ROS sources. Mitochondrial ROS, in
      this setting, act as important signaling molecules activating prothrombotic and
      proinflammatory pathways in the vascular endothelium, a process that initially
      manifests itself as endothelial dysfunction and, if persistent, may lead to the
      development of atherosclerotic plaques. This review concentrates on emerging
      appreciation of the importance of mitochondrial ROS as cell-signaling molecules
      in the vascular endothelium under both physiologic and pathophysiologic
      conditions. Future potential avenues of research in this field also are
      discussed.

PMID- 21194356
TI  - Expression and spatial heterogeneity of dipeptidyl peptidases in endothelial
      cells of conduct vessels and capillaries.
AB  - Dipeptidyl peptidase IV (DPPIV)/CD26 is by far the most extensively studied
      member of the prolyl oligopeptidase family of serine proteases. The discovery of
      the related enzymes DPP8 and DPP9 necessitates a (re-)evaluation of the DPPIV
      like enzymatic activity in cells and organs. In this study, we aimed (1) to
      investigate the expression of the individual dipeptidyl peptidases in different
      types of endothelial cells (ECs) and (2) to reconsider published data in relation
      to our findings. Examination of DPP expression in rat primary ECs of aortic,
      endocardial and cardiac microvascular origin revealed the presence of DPPIV-like
      activity in all cell lysates. More than half of this activity could be attributed
      to DPP8/9. Western blot analysis revealed an abundance of the DPP8 protein as
      compared to DPP9. The expression of DPPIV and DPP8 was significantly higher in
      the cardiac microvascular endothelium than in the other ECs, suggesting a more
      pronounced role of these DPPs in the microvasculature. In situ, DPP activity in
      ventricular microvasculature was completely inhibited by sitagliptin, indicating
      that DPPIV is the predominant DPPIV-like enzyme in this organ. By contrast,
      immunohistochemical studies indicated DPP9 as the predominant DPP in human
      carotid artery ECs. In conclusion, our results support a highly regulated
      expression of individual DPPs in ECs, with a spatial heterogeneity in the
      cardiovascular tree.

PMID- 21194357
TI  - Substance P-induced skin inflammation is not modulated by a single dose of
      sitagliptin in human volunteers.
AB  - Substance P (SP), an undecapeptide belonging to the tachykinin family, is
      released during the activation of sensory nerves, and causes vasodilation, edema
      and pain through activation of tissular Neurokinin 1 receptors. SP
      proinflammatory effects are terminated by angiotensin converting enzyme (ACE) and
      neutral endopeptidase (NEP), while the aminopeptidase dipeptidylpeptidase IV
      (DPPIV) can also play a role. The aim of this randomized, crossover, double-blind
      study was to assess the cutaneous vasoreactivity (flare and wheal reaction,
      burning pain sensation) to intradermal injection of ascending doses of SP in six
      volunteers receiving a single therapeutic dose of the DPPIV inhibitor sitagliptin
      or a matching placebo. Cutaneous SP challenges produced the expected, dose
      dependent flare and wheal response, while eliciting mild to moderate local pain
      sensation with little dose dependency. However, no differences were shown in the
      responses observed under sitagliptin compared with placebo, while the study would
      have been sufficiently powered to detect a clinically relevant increase in
      sensitivity to SP. The results of this pilot study are in line with proteolytic
      cleavage of SP by ACE and NEP compensating the blockade of DPPIV to prevent an
      augmentation of its proinflammatory action.

PMID- 21194358
TI  - Structure determination of channel and transport proteins by high-resolution
      microscopy techniques.
AB  - High-resolution microscopy techniques provide a plethora of information on
      biological structures from the cellular level down to the molecular level. In
      this review, we present the unique capabilities of transmission electron and
      atomic force microscopy to assess the structure, oligomeric state, function and
      dynamics of channel and transport proteins in their native environment, the lipid
      bilayer. Most importantly, membrane proteins can be visualized in the frozen
      hydrated state and in buffer solution by cryo-transmission electron and atomic
      force microscopy, respectively. We also illustrate the potential of the
      scintillation proximity assay to study substrate binding of detergent-solubilized
      transporters prior to crystallization and structural characterization.

PMID- 21194355
TI  - Peroxiredoxins in plants and cyanobacteria.
AB  - Peroxiredoxins (Prx) are central elements of the antioxidant defense system and
      the dithiol-disulfide redox regulatory network of the plant and cyanobacterial
      cell. They employ a thiol-based catalytic mechanism to reduce H2O2,
      alkylhydroperoxide, and peroxinitrite. In plants and cyanobacteria, there exist 2
      CysPrx, 1-CysPrx, PrxQ, and type II Prx. Higher plants typically contain at least
      one plastid 2-CysPrx, one nucleo-cytoplasmic 1-CysPrx, one chloroplast PrxQ, and
      one each of cytosolic, mitochondrial, and plastidic type II Prx. Cyanobacteria
      express variable sets of three or more Prxs. The catalytic cycle consists of
      three steps: (i) peroxidative reduction, (ii) resolving step, and (iii)
      regeneration using diverse electron donors such as thioredoxins, glutaredoxins,
      cyclophilins, glutathione, and ascorbic acid. Prx proteins undergo major
      conformational changes in dependence of their redox state. Thus, they not only
      modulate cellular reactive oxygen species- and reactive nitrogen species
      dependent signaling, but depending on the Prx type they sense the redox state,
      transmit redox information to binding partners, and function as chaperone. They
      serve in context of photosynthesis and respiration, but also in metabolism and
      development of all tissues, for example, in nodules as well as during seed and
      fruit development. The article surveys the current literature and attempts a
      mostly comprehensive coverage of present day knowledge and concepts on Prx
      mechanism, regulation, and function and thus on the whole Prx systems in plants.

PMID- 21194359
TI  - Omp85 in eukaryotic systems: one protein family with distinct functions.
AB  - Omp85-like proteins are evolutionary ancient components of bacterial outer
      membranes and their evolutionary offspring. As a consequence, proteins of this
      family can be found in the outer membrane systems of Gram-negative bacteria and
      endosymbiotically derived organelles. In the different membranes, they perform
      distinct functions such as catalyzing protein insertion into or protein transport
      across the bilayer. Here, the knowledge on the Omp85-like proteins in the
      eukaryotic system with regard to structural properties and physiological behavior
      is summarized.

PMID- 21194361
TI  - The lysosomal polypeptide transporter TAPL: more than a housekeeping factor?
AB  - The transporter associated with antigen processing-like (TAPL) is a polypeptide
      transporter translocating cytosolic peptides into the lumen of lysosomes driven
      by ATP hydrolysis. TAPL belongs to the family of ABC transporters and forms a
      homodimer. This ABC transporter not only shows a broad tissue but also a wide
      phylogenetic distribution, because orthologs are still found in nematodes and
      insects. Here, we present the topology, substrate specificity, and distribution
      of this intracellular polypeptide transporter. Additionally, we will discuss its
      proposed physiological functions such as housekeeping together with a specialized
      factor for metabolite storage as well as for the adaptive immunity.

PMID- 21194360
TI  - Evolution of ABC transporters by gene duplication and their role in human
      disease.
AB  - The ATP-binding cassette (ABC) transporter genes represent the largest family of
      transporters and these genes are abundant in the genome of all vertebrates.
      Through analysis of the genome sequence databases we have characterized the full
      complement of ABC genes from several mammals and other vertebrates. Multiple gene
      duplication and deletion events were identified in ABC genes in different
      lineages indicating that the process of gene evolution is still ongoing. Gene
      duplication resulting in either gene birth or gene death plays a major role in
      the evolution of the vertebrate ABC genes. The understanding of this mechanism is
      important in the context of human health because these ABC genes are associated
      with human disease, involving nearly all organ systems of the body. In addition,
      ABC genes play an important role in the development of drug resistance in cancer
      cells. Future genetic, functional, and evolutionary studies of ABC transporters
      will provide important insight into human and animal biology.

PMID- 21194351
TI  - Basic principles and emerging concepts in the redox control of transcription
      factors.
AB  - Convincing concepts of redox control of gene transcription have been worked out
      for prokaryotes and lower eukaryotes, whereas the knowledge on complex mammalian
      systems still resembles a patchwork of poorly connected findings. The article,
      therefore, reviews principles of redox regulation with special emphasis on
      chemical feasibility, kinetic requirements, specificity, and physiological
      context, taking well investigated mammalian transcription factor systems, nuclear
      transcription factor of bone marrow-derived lymphocytes (NF-kappaB), and kelch
      like ECH-associated protein-1 (Keap1)/Nrf2, as paradigms. Major conclusions are
      that (i) direct signaling by free radicals is restricted to O(2)*- and *NO and
      can be excluded for fast reacting radicals such as *OH, *OR, or Cl*; (ii) oxidant
      signals are H(2)O(2), enzymatically generated lipid hydroperoxides, and
      peroxynitrite; (iii) free radical damage is sensed via generation of Michael
      acceptors; (iv) protein thiol oxidation/alkylation is the prominent mechanism to
      modulate function; (v) redox sensors must be thiol peroxidases by themselves or
      proteins with similarly reactive cysteine or selenocysteine (Sec) residues to
      kinetically compete with glutathione peroxidase (GPx)- and peroxiredoxin (Prx)
      type peroxidases or glutathione-S-transferases, respectively, a postulate that
      still has to be verified for putative mammalian sensors. S-transferases and Prxs
      are considered for system complementation. The impact of NF-kappaB and Nrf2 on
      hormesis, management of inflammatory diseases, and cancer prevention is
      critically discussed.

PMID- 21194362
TI  - Novel aspects of cellular action of dipeptidyl peptidase IV/CD26.
AB  - The cellular dipeptidyl peptidase IV (DPIV, E.C.3.4.14.5, CD26) is a type II
      membrane peptidase with various physio-logical functions. Our main knowledge on
      DPIV comes from studies of soluble DPIV which plays a role in regulation of
      glucose homeostasis by inactivation of the incretins glucagon-like peptide-1 and
      glucose-dependent insulinotropic poly-peptide. It has been reported that membrane
      bound DPIV plays a crucial role in the immune system and in other tissues and
      cells, but the knowledge on the action of cellular DPIV and its regulation is
      limited. In this study, we show particularly for immune cells that DPIV and not
      DP8 or DP9 is the most potent member of the DPIV family in regulating cellular
      immune functions. Moreover, we provide evidence that soluble and cellular DPIV
      differ in functions and hand-ling of substrates and inhibitors owing to the
      different accessibility of peptide substrates to the two access paths of DPIV.
      The different functions are based on the favored access path of the central pore
      of cellular DPIV and a special central pore binding site which assists substrate
      access to the active site of the enzyme. The newly discovered central pore
      binding site mediates an autosterical regulation of cellular DPIV and is its most
      crucial target site to regulate cellular functions such as growth and cytokine
      production. Neuropeptide Y (NPY) processing by cellular DPIV was found to be
      inhibited by ligands which interact with the central pore binding site. This
      finding suggests a crucial role of the immunosuppressive cytokine NPY in the
      function of DPIV in growth regulation.

PMID- 21194363
TI  - Substrate recognition and translocation by polyspecific organic cation
      transporters.
AB  - Organic cation transporters (OCTs) of the SLC22 family play a pivotal role in
      distribution and excretion of cationic drugs. They mediate electrogenic
      translocation of cations in both directions. OCTs are polyspecific transporters.
      During substrate translocation they perform a series of conformational changes
      involving an outward-facing conformation, an occluded state and an inward-facing
      conformation. Mutagenesis of OCT1 in combination with homology modeling showed
      that identical amino acids form the innermost parts of the outward-open and
      inward-open binding clefts. In addition to low affinity substrate binding sites,
      OCT1 contains high affinity substrate binding sites that can mediate inhibition
      via non-transported compounds.

PMID- 21194364
TI  - Role of the Ca2+ -activated Cl- channels bestrophin and anoctamin in epithelial
      cells.
AB  - Two families of proteins, the bestrophins (Best) and the recently cloned TMEM16
      proteins (anoctamin, Ano), recapitulate properties of Ca(2+)-activated Cl(-)
      currents. Best1 is strongly expressed in the retinal pigment epithelium and could
      have a function as a Ca(2+)-activated Cl(-) channel as well as a regulator of
      Ca(2+) signaling. It is also present at much lower levels in other cell types
      including epithelial cells, where it regulates plasma membrane localized Cl(-)
      channels by controlling intracellular Ca(2+) levels. Best1 interacts with
      important Ca(2+)-signaling proteins such as STIM1 and can interact directly with
      other Ca(2+)-activated Cl(-) channels such as TMEM16A. Best1 is detected in the
      endoplasmic reticulum (ER) where it shapes the dynamic ER structure and regulates
      cell proliferation, which could be important for renal cystogenesis. Ca(2+)
      activated Cl(-) channels of the anoctamin family (TMEM16A) show biophysical and
      pharmacological properties that are typical for endogenous Ca(2+)-dependent Cl(-)
      channels. TMEM16 proteins are abundantly expressed and many reports demonstrate
      their physiological importance in epithelial as well as non-epithelial cells.
      These channels are also activated by cell swelling and can therefore control cell
      volume, proliferation and apoptosis. To fully understand the function and
      regulation of Ca(2+)-activated Cl(-) currents, it is necessary to appreciate that
      Best1 and TMEM16A are embedded in a protein network and that they probably
      operate in functional microdomains.

PMID- 21194365
TI  - The multidrug transporter Pdr5: a molecular diode?
AB  - A subset of the family of ATP-binding cassette (ABC) transporters has been in
      focus owing to their involvement in conferring multidrug resistance in cancer
      cells and among immune compromised individuals. Saccharomyces cerevisiae is
      protected against xenobiotics by similar machineries that are part of the
      pleitropic drug resistance (PDR) network. The ABC transporter Pdr5 is an
      important member of this PDR network in yeast and is involved in cellular
      detoxification by the efflux of a wide variety of drugs and substrates. In this
      review, we focus on the aspects of detergent effects and the degeneracy in
      conserved sequences that is observed in the nucleotide binding domains of Pdr5
      and discuss their functional relevance.

PMID- 21194366
TI  - A structural and functional analysis of type III periplasmic and substrate
      binding proteins: their role in bacterial siderophore and heme transport.
AB  - In Escherichia coli the Fhu, Fep and Fec transport systems are involved in the
      uptake of chelated ferric iron-siderophore complexes, whereas in pathogenic
      strains heme can also be used as an iron source. An essential step in these
      pathways is the movement of the ferric-siderophore complex or heme from the outer
      membrane transporter across the periplasm to the cognate cytoplasmic membrane ATP
      dependent transporter. This is accomplished in each case by a dedicated
      periplasmic binding protein (PBP). Ferric-siderophore binding PBPs belong to the
      PBP protein superfamily and adopt a bilobal type III structural fold in which the
      two independently folded amino and carboxy terminal domains are linked together
      by a single long alpha-helix of approximately 20 amino acids. Recent structural
      studies reveal how the PBPs of the Fhu, Fep, Fec and Chu systems are able to bind
      their corresponding ligands. These complex structures will be discussed and
      placed in the context of our current understanding of the entire type III family
      of Gram-negative periplasmic binding proteins and related Gram-positive substrate
      binding proteins.

PMID- 21194367
TI  - Evolution of YidC/Oxa1/Alb3 insertases: three independent gene duplications
      followed by functional specialization in bacteria, mitochondria and chloroplasts.
AB  - Members of the YidC/Oxa1/Alb3 protein family facilitate the insertion, folding
      and assembly of proteins of the inner membranes of bacteria and mitochondria and
      the thylakoid membrane of plastids. All homologs share a conserved hydrophobic
      core region comprising five transmembrane domains. On the basis of phylogenetic
      analyses, six subgroups of the family can be distinguished which presumably arose
      from three independent gene duplications followed by functional specialization.
      During evolution of bacteria, mitochondria and chloroplasts, subgroup-specific
      regions were added to the core domain to facilitate the association with
      ribosomes or other components contributing to the substrate spectrum of
      YidC/Oxa1/Alb3 proteins.

PMID- 21194368
TI  - SLC22 transporter family proteins as targets for cytostatic uptake into tumor
      cells.
AB  - The response to chemotherapy by tumor cells depends on the concentration of
      cytostatics accumulated inside the cells. The accumulation of anticancer drugs in
      tumor cells is mainly dependent on functional expression of efflux and influx
      transporters and to a minor extent on passive diffusion through the membrane.
      Efflux transporters of the ABC family are partially responsible for the
      chemoresistance of cancer cells by secreting these cytostatics. Over the past
      decades, the role of ABC transporters in the chemoresistance of various malignant
      tumors has been very well documented. By contrast, very little is known about the
      impact on tumor therapy of influx transporters belonging to the solute carrier
      transporters (SLC family). In this review, we focus on the interaction of SLC22
      transporters with cytostatics, the expression of these transporters in tumor
      cells as well as their impact on the chemosensitivity of cancer cells.

PMID- 21194369
TI  - Pumping lipids with P4-ATPases.
AB  - While accumulating evidence indicates that P4-ATPases catalyze phospholipid
      transport across cellular bilayers, their kinship to cation-pumping ATPases has
      raised fundamental questions concerning the underlying flippase mechanism. Loss
      of P4-ATPase function perturbs vesicle formation in late secretory and endocytic
      compartments. An intriguing concept is that P4-ATPases help drive vesicle budding
      by generating imbalances in transbilayer lipid numbers. Moreover, activation of
      P4-ATPases by phosphoinositides and other effectors of coat recruitment provide a
      potential mechanism to confine flippase activity to sites of vesicle biogenesis.
      These developments have raised considerable interest in understanding the
      mechanism, regulation and biological implications of P4-ATPase-catalyzed
      phospholipid transport.

PMID- 21194371
TI  - Transporters, Trojan horses and therapeutics: suitability of bile acid and
      peptide transporters for drug delivery.
AB  - Membrane transporters are major determinants for the pharmacokinetic, safety and
      efficacy behavior of drugs. Available technologies to study function and
      structure of transport proteins has strongly stimulated research in transporter
      biology and uncovered their importance for the drug discovery and development
      process, especially for drug absorption and disposition. Physiological transport
      systems are investigated as potential ferries to improve drug absorption and
      membrane permeation and to achieve organ-specific drug action. In particular, the
      bile acid transport systems in the liver and the small intestine and the
      oligopeptide transporters are of significant importance for molecular drug
      delivery.

PMID- 21194370
TI  - The ugly side of amphetamines: short- and long-term toxicity of 3,4
      methylenedioxymethamphetamine (MDMA, 'Ecstasy'), methamphetamine and D
      amphetamine.
AB  - Amphetamine ('Speed'), methamphetamine ('Ice') and its congener 3,4
      methylenedioxymethamphetamine (MDMA; 'Ecstasy') are illicit drugs abused
      worldwide for their euphoric and stimulant effects. Despite compelling evidence
      for chronic MDMA neurotoxicity in animal models, the physiological consequences
      of such toxicity in humans remain unclear. In addition, distinct differences in
      the metabolism and pharmacokinetics of MDMA between species and different strains
      of animals prevent the rationalisation of realistic human dose paradigms in
      animal studies. Here, we attempt to review amphetamine toxicity and in particular
      MDMA toxicity in the pathogenesis of exemplary human pathologies, independently
      of confounding environmental factors such as poly-drug use and drug purity.

PMID- 21194372
TI  - Pathways of transport protein evolution: recent advances.
AB  - We herein report recent advances in our understanding of transport protein
      evolution. Numerous families of complex transmembrane transport proteins are
      believed to have arisen from short channel-forming amphipathic or hydrophobic
      peptides by various types of intragenic duplication events. Distinct pathways
      distinguish families, demonstrating independent origins for some, and allowing
      assignment of others to superfamilies. Some families have diversified in
      topology, whereas others have remained uniform. An example of 'retroevolution'
      was discovered where a more complex carrier gave rise to a structurally and
      functionally simpler channel. The results described in this review article expand
      our understanding of protein evolution.

PMID- 21194373
TI  - Myeloperoxidase-catalyzed oxidative inactivation of human kininogens: the
      impairment of kinin-precursor and prekallikrein-binding functions.
AB  - Bradykinin-related vasoactive peptides (kinins) are important mediators of local
      and systemic inflammatory reactions. However, at local inflammatory foci, the
      production of kinins from proteinaceous precursors (kininogens) can be affected
      by reactive oxygen species released by phagocyte cells. One of the predominant
      oxidants at these places is hypochlorous acid which is formed from hydrogen
      peroxide and chloride ions by neutrophil myeloperoxidase. In this study,
      inactivation of human kininogens after oxidation with the myeloperoxidase-H2O2
      chloride system was observed and analyzed by protein chemistry methods. The kinin
      release from oxidized kininogens by major kinin-producing enzymes, plasma and
      tissue kallikreins, proceed with a very low rate. This effect was assigned to
      apparent inability of kallikreins to process the kinin N-terminus owing to the
      conversion of the adjacent Met-361 residue to methionine sulfoxide. Additionally,
      the oxidized high-molecular mass kininogen lost its natural ability to bind
      plasma prekallikrein. This effect was assigned to the oxidation of Trp-569
      residue within the prekallikrein-binding region which is subsequently destructed
      owing to cleavage of the peptide bond after that residue. One possible
      pathophysiological consequence of the described effects on kininogens could be
      the impairment of the normal assembly and triggering of the kinin-forming system
      on defense cell surfaces.

PMID- 21194374
TI  - Identification and characterisation of novel Mss4-binding Rab GTPases.
AB  - The Mss4 (mammalian suppressor of yeast Sec4) is an evolutionarily highly
      conserved protein and is expressed in all mammalian tissues. Although its precise
      biological function is still elusive, it has been shown to associate with a
      subset of secretory Rab proteins (Rab1b, Rab3a, Rab8a, Rab10) and to possess a
      rather low guanine nucleotide exchange factor (GEF) activity towards them in
      vitro (Rab1, Rab3a and Rab8a). By screening a human placenta cDNA library with
      Mss4 as bait, we identified several Rab GTPases (Rab12, Rab13 and Rab18) as novel
      Mss4-binding Rab proteins. Only exocytic but no endocytic Rab GTPases were found
      in our search. The binding of Mss4 to Rab proteins was confirmed by direct yeast
      two-hybrid interaction, by co-immunoprecipitation from lysates of mammalian
      cells, by immunofluorescence colocalisation as well as by direct in vitro binding
      studies. Analysis of Mss4 catalytic activity towards different Rab substrates
      confirmed that it is a somewhat inefficient GEF. These data, together with our
      mutational analysis of Mss4-Rab binding capacity, support the already proposed
      idea that Mss4 functions rather as a chaperone for exocytic Rab GTPases than as a
      GEF.

PMID- 21194375
TI  - Antiangiogenic kringles derived from human plasminogen and apolipoprotein(a)
      inhibit fibrinolysis through a mechanism that requires a functional lysine
      binding site.
AB  - Many proteins in the fibrinolysis pathway contain antiangiogenic kringle domains.
      Owing to the high degree of homology between kringle domains, there has been a
      safety concern that antiangiogenic kringles could interact with common kringle
      proteins during fibrinolysis leading to adverse effects in vivo. To address this
      issue, we investigated the effects of several antiangiogenic kringle proteins
      including angiostatin, apolipoprotein(a) kringles IV(9)-IV(10)-V (LK68),
      apolipoprotein(a) kringle V (rhLK8) and a derivative of rhLK8 mutated to produce
      a functional lysine-binding site (Lys-rhLK8) on the entire fibrinolytic process
      in vitro and analyzed the role of lysine binding. Angiostatin, LK68 and Lys-rhLK8
      increased clot lysis time in a dose-dependent manner, inhibited tissue-type
      plasminogen activator-mediated plasminogen activation on a thrombin-modified
      fibrinogen (TMF) surface, showed binding to TMF and significantly decreased the
      amount of plasminogen bound to TMF. The inhibition of fibrinolysis by these
      proteins appears to be dependent on their functional lysine-binding sites.
      However, rhLK8 had no effect on these processes owing to an inability to bind
      lysine. Collectively, these results indicate that antiangiogenic kringles without
      lysine binding sites might be safer with respect to physiological fibrinolysis
      than lysine-binding antiangiogenic kringles. However, the clinical significance
      of these findings will require further validation in vivo.

PMID- 21194377
TI  - PETIR-001, a dual inhibitor of dipeptidyl peptidase IV (DP IV) and aminopeptidase
      N (APN), ameliorates experimental autoimmune encephalomyelitis in SJL/J mice.
AB  - Cellular dipeptidyl peptidase IV (DP IV, CD26) and amino-peptidase N (APN, CD13)
      play regulatory roles in T cell activation and represent potential targets for
      treatment of inflammatory disorders. We have developed a novel therapeutic
      strategy, 'peptidase-targeted Immunoregulation' (PETIRTM), which simultaneously
      targets both cellular DP IV and APN via selective binding sites different from
      the active sites with a single inhibitor. To prove the therapeutic concept of
      PETIRTM in autoimmunity of the central nervous system (CNS), we evaluated the
      effect of a single substance, PETIR-001, in an animal model of multiple
      sclerosis, experimental autoimmune encephalomyelitis (EAE) in SJL/J mice.
      Administration of PETIR-001 significantly delayed and decreased clinical signs of
      active EAE, when given in a therapeutic manner intraperitoneally from day 15 to
      day 24 after induction of EAE. Both the acute phase and the first relapse of EAE
      were markedly inhibited. Importantly, a similar therapeutic benefit was obtained
      after oral administration of PETIR-001 from day 12 to day 21 after disease
      induction. Our results demonstrate that PETIR-001 exhibits a therapeutic effect
      on EAE in SJL/J mice. Thus, PETIRTM represents a novel and efficient therapeutic
      approach for immunotherapy of CNS inflammation.

PMID- 21194376
TI  - Hsp90 regulates NADPH oxidase activity and is necessary for superoxide but not
      hydrogen peroxide production.
AB  - The goal of this study was to identify whether heat-shock protein 90 (Hsp90)
      regulates the production of superoxide and other reactive oxygen species from the
      NADPH oxidases (Nox). We found that pharmacological and genetic inhibition of
      Hsp90 directly reduced Nox5-derived superoxide without secondarily modifying
      signaling events. Coimmunoprecipitation and bioluminescence resonance energy
      transfer studies suggest that the C-terminus of Nox5 binds to Hsp90. Long-term
      Hsp90 inhibition reduced Nox5 expression and provides further evidence that Nox5
      is an Hsp90 client protein. Inhibitors of Hsp90 also reduced superoxide from
      Nox1, Nox2 (neutrophils), and Nox3. However, Nox4, which emits only hydrogen
      peroxide, was unaffected by Hsp90 inhibitors. Hydrogen peroxide production from
      the other Nox enzymes was not affected by short-term inhibition of Hsp90, but
      long-term inhibition reduced production of all reactive oxygen species coincident
      with loss of enzyme expression. Expression of chimeric Nox enzymes consisting of
      N-terminal Nox1 or Nox3 and C-terminal Nox4 resulted in only hydrogen peroxide
      formation that was insensitive to Hsp90 inhibitors. We conclude that Hsp90 binds
      to the C-terminus of Noxes1-3 and 5 and is necessary for enzyme stability and
      superoxide production. Hsp90 does not bind to the C-terminus of Nox4 and is not
      required for hydrogen peroxide formation.

PMID- 21194378
TI  - Outside or inside: role of the subcellular localization of DP4-like enzymes for
      substrate conversion and inhibitor effects.
AB  - The discovery of the DP4-related enzymes DP8 and DP9 raised controversial
      discussion regarding the physiological and pathophysiological function of
      distinct members of the DP4 family. Particularly with regard to their potential
      relevance in regulating immune functions, it is of interest to know which role
      the subcellular distribution of the enzymes play. Synthetic substrates as well as
      low molecular weight inhibitors are widely used as tools, but little is yet known
      regarding their features in cell experiments, such as their plasma membrane
      penetration capacity. The fluorogenic substrates Gly-Pro-AMC or (Ala-Pro)2-R110
      predominantly detect plasma membrane-bound activities of viable cells (less than
      0.1% of fluorochromes R110 or AMC inside viable cells after 1 h incubation).
      Additionally, the selective and non-selective DP8/9 inhibitors allo-Ile
      isoindoline and Lys[Z(NO2)]-pyrrolidide were found to be incapable of passing the
      plasma membrane easily. This suggests that previously reported cellular effects
      are not due to inhibition of the cytosolic enzymes DP8 or DP9. Moreover, our
      enzymatic studies with viable cells provided evidence that DP8 and/or DP9 are
      also present on the surface of immune cells under certain circumstances and could
      gain relevance particularly in the absence of DP4 expression. In summary, in
      cells which do express DP4 on the surface, this archetypical member of the DP4
      family is the most relevant peptidase in the regulation of cellular functions.

PMID- 21194379
TI  - Mitochondria autophagy in yeast.
AB  - The mitochondrion is an organelle that carries out a number of important
      metabolic processes such as fatty acid oxidation, the citric acid cycle, and
      oxidative phosphorylation. However, this multitasking organelle also generates
      reactive oxygen species (ROS), which can cause oxidative stress resulting in self
      damage. This type of mitochondrial damage can lead to the further production of
      ROS and a resulting downward spiral with regard to mitochondrial capability. This
      is extremely problematic because the accumulation of dysfunctional mitochondria
      is related to aging, cancer, and neurodegenerative diseases. Accordingly,
      appropriate quality control of this organelle is important to maintain proper
      cellular homeostasis. It has been thought that selective mitochondria autophagy
      (mitophagy) contributes to the maintenance of mitochondrial quality by
      eliminating damaged or excess mitochondria, although little is known about the
      mechanism. Recent studies in yeast identified several mitophagy-related proteins,
      which have been characterized with regard to their function and regulation. In
      this article, we review recent advances in the physiology and molecular mechanism
      of mitophagy and discuss the similarities and differences of this degradation
      process between yeast and mammalian cells.

PMID- 21194380
TI  - Role of SIRT1-FoxO1 signaling in dietary saturated fat-dependent upregulation of
      liver adiponectin receptor 2 in ethanol-administered mice.
AB  - The aim of the present study is to examine the effects of dietary saturated fatty
      acids on liver adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2
      (AdipoR2) in ethanol-administered animals and in ethanol-exposed cultured hepatic
      cells, and to explore the underlying molecular mechanisms. The mRNA and protein
      levels of hepatic AdipoR2 were selectively increased by chronic ethanol feeding
      to mice consuming a diet high in saturated fat (HSF). Administration of an HSF
      diet blocked hyperacetylation of forkhead transcription factor 1 (FoxO1), a known
      target of sirtuin 1 (SIRT1), increased nuclear FoxO1 protein levels, and enhanced
      association of FoxO1 with the AdipoR2 promoter in the livers of ethanol-fed mice.
      Treatment of cultured hepatic cells with palmitic acid (a major saturated fatty
      acid in HSF diet) in the presence of ethanol robustly increased AdipoR2 mRNA
      expression and enhanced activity of a mouse AdipoR2 promoter. Knocking down SIRT1
      or FoxO1 using the small silencing SIRT1 or FoxO1 plasmid blunted the palmitic
      acid effect. Taken together, these results reveal that dietary saturated fat
      selectively upregulates hepatic AdipoR2 through modulation of SIRT1-FoxO1
      signaling in ethanol fed mice, and this effect may contribute to the protective
      effect of the HSF diet against alcoholic fatty liver.

PMID- 21194383
TI  - Stationary-phase mitophagy in respiring Saccharomyces cerevisiae.
AB  - The clearance of malfunctioning mitochondria is an important housekeeping
      function in respiring eukaryotic cells and plays a role in physiological
      homeostasis as well as in the progression of late-onset diseases. This clearance
      is thought to occur by a specific form of autophagic degradation called
      mitophagy. Although the mechanism of nonspecific macroautophagy is relatively
      well established, the selective autophagic degradation of mitochondria has only
      recently begun to receive significant attention. An important step toward
      elucidating the mechanism by which defective mitochondria are selected and
      degraded is the establishment of conditions under which mitophagy is induced.
      This review covers our current understanding of mitophagy in the model organism
      Saccharomyces cerevisiae and its modes of activation, with a focus on stationary
      phase mitophagy-a form of mitophagy that holds promise as a potential quality
      control mechanism.

PMID- 21194382
TI  - Redox control and interplay between p53 isoforms: roles in the regulation of
      basal p53 levels, cell fate, and senescence.
AB  - The p53 tumor suppressor protein has achieved stardom in molecular oncology owing
      to frequent inactivation in a large range of cancers. Known as a factor activated
      by multiple forms of stress and causing a broad suppressive response to DNA
      damage, its regulation and functions in basal (non-stress) conditions has
      received relatively little attention. We summarize recent findings highlighting
      roles of p53 in physiological processes such as stem cell maintenance,
      development, aging and senescence, and regulation of basal oxidative cell
      metabolism. We suggest that these properties are regulated through two integrated
      biochemical systems: the redox-sensing capacity of the p53 protein (due to its
      structural features and its regulation by redox factors such as thioredoxin,
      metallothioneins, or the redox-repair enzyme APE1/ref-1), and the expression of
      p53 as multiple isoforms with antagonist effects. We propose that interactions
      between p53 and its isoforms Delta40p53 or Delta133p53 play critical roles in
      intracellular signaling by reactive oxygen species. We also discuss evidence that
      p53 controls energy production by repressing glycolysis and enhancing
      mitochondrial oxidative metabolism. Together, these mechanisms suggest that p53
      acts not only as a "guardian of the genome" against DNA damage but also as a
      finely-tuned regulator of redox-dependent physiological processes.

PMID- 21194381
TI  - Targeting mitochondrial dysfunction: role for PINK1 and Parkin in mitochondrial
      quality control.
AB  - Mitochondria, which convert energy for the cell, accumulate damage with age, and
      the resulting mitochondrial dysfunction has been linked to the development of
      degenerative diseases and aging. To curb the accumulation of damaged
      mitochondria, the cell has elaborated a number of mitochondrial quality control
      processes. We describe recent work suggesting that Parkin and PTEN-induced
      putative kinase 1 (PINK1), two gene products linked to familial forms of
      parkinsonism, may constitute one of the cell's mitochondrial quality control
      pathways-identifying impaired mitochondria and selectively trimming them from the
      mitochondrial network by mitophagy. In particular, we discuss the regulation of
      PINK1 protein expression and Parkin localization by the bioenergetic status of
      individual mitochondria; the mechanism by which PINK1 recruits Parkin to the
      outer mitochondrial membrane; and Parkin's promotion of mitophagy through its
      ubiquitination of outer mitochondrial membrane proteins. This recent work
      suggests that Parkin and PINK1 may be among the first mammalian proteins
      identified with a direct role in regulating mitophagy, and implicate a failure of
      mitophagy in the pathogenesis of Parkinson's disease.

PMID- 21194384
TI  - Transcriptional profile of genes involved in oxidative stress and antioxidant
      defense in a dietary murine model of steatohepatitis.
AB  - Oxidative stress is a core abnormality responsible for disease progression in
      nonalcoholic steatohepatitis (NASH). However, the relevant pathways that
      contribute to oxidative damage in vivo remain poorly understood. Here we explore
      the gene-expression patterns related to oxidative stress, antioxidant defense,
      and reactive oxygen metabolism in an established dietary murine model of NASH.
      C57BL/6 mice were placed on either a methionine- and choline-deficient (MCD) or a
      control (CTL) diet for 6 weeks. Hepatic oxidative damage and the development of
      NASH were monitored by biochemical and histologic indices. Analysis of 84
      oxidative stress-related genes was performed by real-time reverse transcription
      polymerase chain reaction (PCR) in the livers of the two groups of mice. Mice on
      the MCD diet showed increased ALT, histologic features of NASH, and oxidative
      liver damage with increases in 4-hydroxynonenal and 3-nitrotyrosine. Of the genes
      analyzed, the GPx family were most significantly upregulated, whereas SCD1 was
      most significantly downregulated. Other genes that were significantly upregulated
      included Fmo2 and peroxiredoxins, whereas genes downregulated included Catalase
      and Serpinb1b. Our data demonstrate that oxidative stress-related genes are
      differentially expressed in the livers of mice with diet-induced NASH. These
      findings have important implications for NASH pathogenesis and the development of
      novel therapeutic strategies for patients with this condition.

PMID- 21194385
TI  - Cortical neurons develop insulin resistance and blunted Akt signaling: a
      potential mechanism contributing to enhanced ischemic injury in diabetes.
AB  - Patients with diabetes are at higher risk of stroke and experience increased
      morbidity and mortality after stroke. We hypothesized that cortical neurons
      develop insulin resistance, which decreases neuroprotection via circulating
      insulin and insulin-like growth factor-I (IGF-I). Acute insulin treatment of
      primary embryonic cortical neurons activated insulin signaling including
      phosphorylation of the insulin receptor, extracellular signal-regulated kinase
      (ERK), Akt, p70S6K, and glycogen synthase kinase-3beta (GSK-3beta). To mimic
      insulin resistance, cortical neurons were chronically treated with 25 mM glucose,
      0.2 mM palmitic acid (PA), or 20 nM insulin before acute exposure to 20 nM
      insulin. Cortical neurons pretreated with insulin, but not glucose or PA,
      exhibited blunted phosphorylation of Akt, p70S6K, and GSK-3beta with no change
      detected in ERK. Inhibition of the phosphatidylinositol 3-kinase (PI3-K) pathway
      during insulin pretreatment restored acute insulin-mediated Akt phosphorylation.
      Cortical neurons in adult BKS-db/db mice exhibited higher basal Akt
      phosphorylation than BKS-db(+) mice and did not respond to insulin. Our results
      indicate that prolonged hyperinsulinemia leads to insulin resistance in cortical
      neurons. Decreased sensitivity to neuroprotective ligands may explain the
      increased neuronal damage reported in both experimental models of diabetes and
      diabetic patients after ischemia-reperfusion injury.

PMID- 21194387
TI  - Adipokines and redox signaling: impact on fatty liver disease.
AB  - Adipokines (adipose tissue cytokines) are polypeptide factors secreted by adipose
      tissue in a highly regulated manner. The 'classical' adipokines (leptin,
      adiponectin, and resistin) are expressed only by adipocytes, but other adipokines
      have been shown to be released by resident and infiltrating macrophages, as well
      as by components of the vascular stroma. Indeed, adipose tissue inflammation is
      known to be associated with a modification in the pattern of adipokine secretion.
      Several studies indicate that adipokines can interfere with hepatic injury
      associated with fatty infiltration, differentially modulating steatosis,
      inflammation, and fibrosis. Moreover, plasma levels of adipokines have been
      investigated in patients with nonalcoholic fatty liver disease in order to
      establish correlations with the underlying state of insulin resistance and with
      the type and severity of hepatic damage. In this Forum article, we provide a
      review of recent data that suggest a significant role for oxidative stress,
      reactive oxygen species, and redox signaling in mediating actions of adipokines
      that are relevant in the pathogenesis of nonalcoholic fatty liver disease,
      including hepatic insulin resistance, inflammation, and fibrosis.

PMID- 21194386
TI  - Induced pluripotent stem cells: emerging techniques for nuclear reprogramming.
AB  - Introduction of four transcription factors, Oct3/4, Sox2, Klf4, and c-Myc, can
      successfully reprogram somatic cells into embryonic stem (ES)-like cells. These
      cells, which are referred to as induced pluripotent stem (iPS) cells, closely
      resemble embryonic stem cells in genomic, cell biologic, and phenotypic
      characteristics, and the creation of these special cells was a major triumph in
      cell biology. In contrast to pluripotent stem cells generated by somatic cell
      nuclear-transfer (SCNT) or ES cells derived from the inner cell mass (ICM) of the
      blastocyst, direct reprogramming provides a convenient and reliable means of
      generating pluripotent stem cells. iPS cells have already shown incredible
      potential for research and for therapeutic applications in regenerative medicine
      within just a few years of their discovery. In this review, current techniques of
      generating iPS cells and mechanisms of nuclear reprogramming are reviewed, and
      the potential for therapeutic applications is discussed.

PMID- 21194388
TI  - HMGB1 and microparticles as mediators of the immune response to cell death.
AB  - In a wide variety of diseases, cell death represents both an outcome and an
      important step in pathogenesis. This duality occurs because cell death leads to
      the extracellular release of molecules and structures that can potently induce
      the innate immune system. These mediators include the alarmins which are
      endogenous cellular constituents that exit activated or dying cells to stimulate
      toll-like receptors (TLRs) as well as non-TLR receptors. Of alarmins, the
      nonhistone protein HMGB1 is the prototype. Like DNA and RNA, HMGB1 can
      translocate from cells as they die. The activity of HMGB1 may reflect its
      interaction with other molecules such as LPS, DNA, and cytokines. In addition to
      alarmins, dead and dying cells can release subcellular organelles called
      microparticles that contain cytoplasmic and nuclear constituents, including DNA
      and RNA. These particles can impact on many cell types to induce inflammation.
      The release of HMGB1 and microparticles shows important similarities, occurring
      with cell death as well as stimulation of certain but not all TLRs. Furthermore,
      nitric oxide can induce the release of both. These observations suggest that the
      products of dead cells can serve as important mediators to drive immune responses
      and promote inflammation and autoreactivity.

PMID- 21194390
TI  - The prevalence, correlates and treatment of pain in the European Union.
AB  - OBJECTIVES: To report on the results of a recent large-scale, internet-based
      survey of the population, prevalence and attributes of pain experience in the
      United Kingdom (UK), France, Spain, Germany and Italy. METHODS: The results
      reported here are taken from the internet-based, 2008 National Health and
      Wellness Survey (NHWS). In addition to detailing the prevalence of pain, the
      survey reports on the correlates of pain - socio-demographic characteristics of
      respondents, health status and health related quality of life, pain associated
      comorbidities, satisfaction with care, employment and productivity and
      utilization of health care resources. In addition, the survey also captures
      treatment patterns, satisfaction with medications (both prescription and over the
      counter [OTC]) and adherence experience. RESULTS: An estimated 49.7 million
      persons in these five countries reported pain by both its severity and frequency
      in the previous month. Of these, 11.2 million reported severe pain, 29.4 million
      reported moderate pain and 9.0 million reported mild pain. The population
      prevalence of daily pain is 8.85% with 3.47% reporting severe daily pain and
      4.70% moderate daily pain. The cumulative burden of pain is demonstrated in terms
      of HRQoL, employment status and workforce activities as well as in healthcare
      resource utilization. The most striking impacts are seen in the impact of severe
      and frequent pain on HRQoL. Of the measures employed, the impact on the physical
      component score (PCS) of the SF-12 and the SF-6D absolute utility scores are
      substantial. The presence of severe and daily pain not only reduces the PCS score
      against that reported for the no pain population by over 20 points (or
      approximately 40%) but the impact on the absolute utility score is to reduce it
      from a no pain average of 0.74 to a score of 0.54. As far as productivity losses
      to the community are concerned the impact of severe pain is equally dramatic.
      CONCLUSIONS: The reported prevalence of pain in these five countries represents a
      substantial burden to individuals, employers, healthcare systems and society in
      general. The fact that one in five of the adult population has experienced pain
      presents a major policy challenge. This would involve not only reducing the
      prevalence of pain - where chronic pain may be considered a disease in its own
      right - but to co-ordinate pain management programs across a range of disease
      states and socio-economic groups.

PMID- 21194389
TI  - Very small embryonic-like stem cells: biology and therapeutic potential for heart
      repair.
AB  - Very small embryonic-like stem cells (VSELs) represent a population of extremely
      small nonhematopoietic pluripotent cells that are negative for lineage markers
      and express Sca-1 in mice and CD133 in humans. Their embryonic-like
      characteristics include the expression of markers of pluripotency; the ability to
      give rise to cellular derivatives of all three germ-layers; and the ability to
      form embryoid-like bodies. Indeed, quiescent VSELs may represent the remnants of
      epiblast-derived cells in adult organs. After tissue injury, including acute
      myocardial infarction (MI), bone marrow-derived VSELs are mobilized into the
      peripheral blood and home to the damaged organ. Given the ability of VSELs to
      differentiate into cardiomyocytes and endothelial cells, and their ability to
      secrete various cardioprotective growth factors/cytokines, VSELs may serve as an
      ideal cellular source for cardiac repair. Consistently, transplantation of VSELs
      after an acute MI improves left ventricular (LV) structure and function, and
      these benefits remain stable during long-term follow-up. Although the mechanisms
      remain under investigation, effects of secreted factors, regeneration of cellular
      constituents, and stimulation of endogenous stem/progenitors may play
      combinatorial roles. The purpose of this review is to summarize the current
      evidence regarding the biologic features of VSELs, and to discuss their potential
      as cellular substrates for therapeutic cardiac repair.

PMID- 21194391
TI  - Patient experience with darifenacin - results of a short-term community-based
      survey in managing overactive bladder.
AB  - OBJECTIVE: This community-based program evaluated patients' experiences with
      darifenacin over 3 weeks' treatment in a predominantly primary care clinical
      practice setting. METHODS: Physicians (n = 2117, 50% primary care physicians, 35%
      urologists, 10% obstetrician/gynecologist, 5% other) were asked to introduce the
      program to patients with overactive bladder (OAB). Patients received an
      enrollment kit including a 30-day darifenacin voucher, activated if patients
      registered for the program via telephone or online. Patients (>= 18 years of age)
      completed a brief automated survey to evaluate frequency of urge urinary
      incontinence episodes (UUIEs), micturitions/24 hours, urge severity/24 hours (10
      point scale: 0 = not at all severe; 10 = very severe), and treatment tolerability
      (10 point scale: 0 = very poorly tolerated; 10 = very well tolerated). Patients
      also completed a second survey 3 weeks after starting darifenacin. Statistical
      analyses were not prospectively planned or performed. RESULTS: A total of 2165
      patients completed both surveys. At baseline, mean age of completers was 66
      years, 76% were female, and 47% reported prior use of OAB medications. After 3
      weeks' treatment, patients experienced reductions in UUIEs and micturitions. Urge
      severity was reduced by >30% after 3 weeks (mean scores: 6.7 at baseline vs. 4.6
      after 3 weeks' treatment) and treatment was well tolerated (mean score: 7.7).
      Overall, 85% of patients who participated in the program did so due to physician
      influences. CONCLUSIONS: The results of this 3-week, self-reported community
      based survey indicate that patients were generally satisfied with darifenacin
      treatment and experienced a reduction in OAB symptoms. Darifenacin was generally
      well tolerated.

PMID- 21194392
TI  - Opioids: a two-faced Janus.
AB  - BACKGROUND: Long-term pain is a debilitating condition that is costly to treat
      and has a significant impact on patient quality of life. Classical opioids have
      been used for the treatment of pain for centuries and are one of the most
      effective drug classes available for acute severe pain and long-term pain.
      However, concerns regarding adverse effects, tolerance to analgesic effects and
      the potential for addiction have resulted in a reluctance to prescribe and use
      opioids for the management of long-term non-cancer pain. Adverse events,
      including gastrointestinal side effects such as constipation, nausea and
      vomiting, and central nervous system side effects such as sedation are
      responsible for as many as one in five patients discontinuing opioid treatment,
      often leading to inadequate pain relief and poor patient quality of life.
      Therefore, new analgesic therapies are needed that are associated with fewer
      adverse effects, whilst providing sustainable pain relief for patients with long
      term pain. OBJECTIVE AND METHODS: To provide an overview of the historical
      development, uses, mechanisms of action, receptor affinities and side-effect
      profiles of classical opioids. In addition, recent developments and novel
      approaches for long-term, severe pain treatment are also reviewed. RESULTS: A
      number of treatment strategies were identified: co-administration with opioid
      sparing analgesics to reduce side effects and/or risk of dependence, the use of
      peripheral opioid antagonists and novel delivery mechanisms to reduce side
      effects, the development of non-opioid agents that reduce side effects and
      enhance analgesia such as glial cell modulators, and the development of novel
      agents with combined u-receptor and monoaminergic activity within the same
      molecule. CONCLUSIONS: Despite these recent advances, there have been very few
      completely novel drug developments. Hence, there remains a continuing need for
      innovative therapeutic strategies for the treatment of long-term pain. The most
      promising alternatives appear to be the use of traditional opioids together with
      peripheral opioid antagonists, combining opioids with glial cell modulators, and
      the use of novel agents with u-receptor agonist and noradrenaline reuptake
      inhibitor activity within the same molecule (MOR-NRI compounds).

PMID- 21194393
TI  - Make a CHANGE: optimising communication and pain management decisions.
AB  - The major objectives of the CHANGE PAIN International Advisory Board are to
      enhance understanding of chronic pain and to develop strategies for improving
      pain management. At its second meeting, in November 2009, evidence was presented
      that around one person in five in Europe and the USA experiences chronic pain,
      and the delay before referral to a pain specialist is often several years.
      Moreover, physicians' pharmacological approach to chronic pain is inconsistent,
      as evidenced by the huge variation in treatment between different European
      countries. It was agreed that efficient communication between physician and
      patient is essential for effective pain management, and that efficacy/side-effect
      balance is a key factor in choosing an analgesic agent. The multifactorial nature
      of chronic pain produces various physical and psychological symptoms, so the
      management of chronic pain should be tailored to the individual. Pharmacological
      therapy must be matched to the causative mechanisms responsible, or it is likely
      to prove ineffective and risk the development of a 'vicious circle'; doses are
      increased because of inadequate pain relief, but this increases side-effects so
      doses are reduced, pain relief is then inadequate, so doses are increased, and so
      on. Pain management decisions should not therefore be based solely on the
      severity of pain. Based on the concept of individual treatment targets (ITT), the
      CHANGE PAIN Scale was adopted - a simple, user-friendly assessment tool to
      improve communication between physician and patient. The 11-point NRS enables the
      patient to rate the current pain intensity and to set a realistic individual
      target level. On the reverse are six key parameters affecting the patient's
      quality of life; clinicians simply need to agree with patients whether
      improvement is needed in each one. Regular use can establish the efficacy and
      tolerability of pain management, and the rate of progress towards individual
      treatment targets.

PMID- 21194395
TI  - Effects of specific chemical suppressors of plasminogen activator inhibitor-1 in
      cardiovascular diseases.
AB  - INTRODUCTION: plasminogen activator inhibitor-1 (PAI-1) is critical in thrombus
      formation and inflammation. Although these are essential pathological features of
      cardiovascular diseases, the effects of PAI-1 inhibition against the development
      of cardiovascular remodeling have not been well studied. AREAS COVERED: the
      review explores the therapeutic value of PAI-1 in the progression of various
      cardiovascular diseases. To date, the authors have reported that a novel PAI-1
      inhibitor suppressed the development of experimental autoimmune myocarditis,
      vascular remodeling after arterial injury, and heart transplant rejection using
      rodent models. Pathologically, the PAI-1 inhibitor improved histological
      remodeling of myocardium and arteries with suppression of inflammation and
      thrombus formation. EXPERT OPINION: PAI-1 inhibitors appear to exhibit potent
      effects on the prevention of adverse tissue remodeling. However, PAI-1 is a
      multifunctional protein and more research is needed to further elucidate the
      association between PAI-1 expression and cardiovascular disease.

PMID- 21194394
TI  - Epidemiology of chronic non-cancer pain in Europe: narrative review of
      prevalence, pain treatments and pain impact.
AB  - BACKGROUND: Estimates on the epidemiology of chronic non-cancer pain vary widely
      throughout Europe. It is unclear whether this variation reflects true population
      differences or methodological factors. Such epidemiological information supports
      European decision makers in allocating healthcare resources. OBJECTIVE: Pan
      Europe epidemiological data about chronic non-cancer pain was obtained using
      systematic review principles in searching and summarising results. METHODS:
      Multiple databases (MEDLINE, EMBASE, Cochrane Library, CRD Databases, and GIN)
      were systematically searched for primary studies containing epidemiological data
      on chronic non-cancer pain in Europe excluding studies that solely concerned
      migraines, headaches and pain associated with specific disease conditions. The
      studies were prioritised according to quality, recency and validity. MAIN
      OUTCOMES: Eighteen research questions concerning aspects of chronic pain
      included: prevalence; incidence; pain treatments, control and compliance;
      treatment satisfaction; and quality of life and economic impacts. RESULTS: The
      search yielded 16 619 references and 45 were relevant to Europe. Studies for each
      question were selected that provided the most recent, representative and valid
      data. There was a clear lack of studies concerning chronic non-cancer pain in
      Europe as a whole. The 1-month prevalence of moderate-to-severe non-cancer
      chronic pain was 19%. Chronic pain significantly impacted on patient-perceived
      health status, affected everyday activities including economic pursuits and
      personal relationships, and was significantly associated with depressive
      symptoms. The majority relied on drugs for pain control and NSAIDs were the most
      frequent drug choice. Despite pain medications, a large proportion had inadequate
      pain control. CONCLUSION: To the authors' knowledge this is the most
      comprehensive literature review on epidemiological data in this field. It is
      clear that chronic pain has a dramatic impact on European society. Since chronic
      non-cancer pain is treated differently from cancer-related pain, the lack of data
      in this area clearly underlines the need for decision makers in healthcare to
      gather further epidemiological data.

PMID- 21194397
TI  - Controversies over the interpretation of changes of mean platelet volume in
      rheumatoid arthritis.

PMID- 21194396
TI  - Can mean platelet volume predict coronary vasospasm?
AB  - Mean platelet volume (MPV) is an index of platelet function that reflects
      platelet production rate and sensitivity to activation. The relationship between
      MPV and coronary vasospasm has not been previously studied. In this study, we
      aimed to evaluate this relationship. A total of 696 patients (age 55.20 +/-
      12.26, male 46.4%, female 53.6%) with typical or atypical angina who underwent
      diagnostic coronary angiography (CAG) and an acetylcholine (Ach)-provocation test
      were enrolled. Each patient was assigned to either an Ach-induced coronary
      vasospasm group (n = 183) or a control group (n = 513). We compared MPV between
      the two groups. MPV and the platelet count showed a negative correlation (r = 
      0.289, p < 0.001). MPV was higher in the Ach-induced coronary vasospasm group
      than in the control group (9.03 +/- 1.37 fl and 8.69 +/- 1.25 fl, respectively, p
      = 0.002). In multivariate analysis, MPV independently predicted Ach-induced
      coronary vasospasm (OR = 1.188, p = 0.018). This study identified high MPV as an
      independent risk factor for Ach-induced coronary vasospasm.

PMID- 21194398
TI  - Platelet membranes induce airway smooth muscle cell proliferation.
AB  - The role of platelets in airway disease is poorly understood although they have
      been suggested to influence on proliferation of airway smooth muscle cells
      (ASMC). Platelets have been found localized in the airways in autopsy material
      from asthmatic patients and have been implicated in airway remodeling. The aim of
      the present study was to investigate the effects of various platelet fractions on
      proliferation of ASMC obtained from guinea pigs (GP-ASMC) and humans (H-ASMC).
      Proliferation of ASMC was measured by the MTS assay and the results confirmed by
      measurements of the DNA content. A key observation was that the platelet membrane
      preparations induced a significant increase in the proliferation of both GP-ASMC
      (129.9 +/- 3.0 %) and H-ASMC (144.8 +/- 12.2). However, neither supernatants from
      lysed or filtrated thrombin stimulated platelets induced ASMC proliferation to
      the same extent as the membrane preparation. We have previously shown that
      platelet-induced proliferation is dependent on 5-lipoxygenase (5-LOX) and
      reactive oxygen species (ROS) pathways. In the present work we established that
      platelet membrane-induced ASMC proliferation was reduced in the presence of the
      NADPH oxidase inhibitor DPI and the 5-LOX inhibitor AA-861. In conclusion, our
      results showed that platelet membranes significantly induced ASMC proliferation,
      demonstrating that the mitogenic effect of platelets and platelet membranes on
      ASMC is mainly due to membrane-associated factors. The effects of platelet
      membranes were evident on both GP-ASMC and H-ASMC and involved 5-LOX and ROS.
      These new findings are of importance in understanding the mechanisms contributing
      to airway remodeling and may contribute to the development of new pharmacological
      tools in the treatment of inflammatory airway diseases.

PMID- 21194399
TI  - Platelet high-density lipoprotein activates transferrin-derived phagocytosis
      activators, MAPPs, following thrombin digestion.
AB  - Macromolecular activators of phagocytosis from platelets (MAPPs), transferrin
      derived phagocytosis activators released from platelets, activate leukocytic
      phagocytosis via Fcgamma receptors. It has been found that MAPPs can be prepared
      using stored platelets or their lysate. Using this artificial MAPP production
      system, it has been found that they can be produced from precursors (tetrameric
      and dimeric transferrins) following reaction with a low-molecular-weight (LMW)
      activator of MAPPs, which is liberated from a high-molecular-weight activator of
      MAPP (HMW activator) by reaction with thrombin. In this study, the HMW activator
      in platelet lysate was characterized by assaying phagocytosis of washed
      neutrophils. In an ultracentrifugation study of the platelet lysate, HMW
      activator activity was observed in the fraction corresponding to the density of
      high-density lipoprotein (HDL). The activity was observed in the apolipoproteins
      obtained from the HDL fraction. Among the apolipoproteins tested only
      apolipoprotein CIII showed the activity to produce MAPP in vitro. Affinity
      chromatography of the apolipoproteins from the HDL fraction of the platelet
      lysate using an anti-apolipoprotein CIII column revealed that the substance that
      binds with the antibody showed MAPP-forming activity. In a gel filtration study
      of thrombin-treated apolipoprotein CIII, a peak of LMW activator activity was
      observed for fractions with a molecular size smaller than that of apolipoprotein
      CIII. Finally, MAPP-forming activity of HDL obtained from the plasma was
      examined. MAPP was formed only when delipidized HDL was used. In conclusion, it
      is suggested that platelet HDL is the HMW activator and that this activation is
      achieved via apolipoprotein CIII after thrombin reaction in platelets.

PMID- 21194400
TI  - Online survey: knowledge about risks, prevention and consequences of infections
      with HBV among travellers from four European countries.
AB  - OBJECTIVE: To evaluate knowledge about risks, prevention and consequences of
      infection with hepatitis B virus (HBV) among travellers from four low HBV risk,
      European countries. METHODS: Individuals from an internet panel and based in the
      Czech Republic, the Netherlands, Spain and Sweden were invited to take part in an
      online survey. A total of 4203 respondents met the inclusion criteria and
      completed the survey. RESULTS: The majority (62.3%) of respondents did not know
      the main travel destinations with moderate or high prevalence for HBV. Also,
      20.1% were somewhat or very unaware of the ways in which HBV can be caught and
      travellers aged 18-35 years were significantly more likely (p < 0.01) to have
      participated in at least one risky activity abroad. Three-quarters (74.9%)
      thought they were somewhat or very aware of the health implications of
      contracting HBV, but only 11.8% of participants selected more than three out of
      the six correct answers relating to conditions caused by HBV. Only 39.3% of those
      who knew their vaccination status had received vaccination against HBV within the
      previous 5 years, although some patients may have been vaccinated prior to this
      period. CONCLUSIONS: As country-specific variables were not analysed in this
      study, the results do not allow interpretation by country. A high proportion of
      the respondents were at an elevated risk of HBV infection while visiting moderate
      or high prevalence countries. They were unlikely to be immunised or take
      appropriate precautions; participation in risk activities abroad was high, and
      knowledge of HBV was limited. These findings indicate there is a need for
      healthcare professionals and the travel industry to educate travellers on the
      risks of HBV infections while abroad and the importance of preventing infection
      through vaccination.

PMID- 21194401
TI  - The interactions of anti-cancer drugs approved in the last decade in the United
      States with membrane transporters.
AB  - Membrane transporters play a role in determining the absorption, distribution,
      metabolism and excretion of small molecule anticancer drugs and mediating
      chemosensitivity and resistance of tumor cells to these drugs. Our understanding
      of the influence of these transporters on the pharmacokinetics, clinical
      effectiveness and tolerability has considerably increased in the last decade.
      Therefore, determining the interaction of membrane transporters with small
      molecule anticancer drugs can facilitate the development of effective and safe
      treatments. We reviewed the interaction of the small molecule anticancer drugs
      approved in the last decade with the more common membranes transporters, such as
      ABCB1, ABCG2, and OATP. The drugs were divided into three categories: targeted
      therapies, cytotoxic agents and hormonal therapies. The literature appears to
      focus on the interaction of the targeted therapies compared to the remaining two
      categories. Furthermore, most data stemmed from nonclinical studies with only a
      few clinical examples where transporters corresponded with systemic exposure or
      clinical effectiveness or tolerability. More nonclinical and clinical studies are
      needed to improve the ability to use the findings from these nonclinical studies
      to predict clinical outcomes, but the literature appears to be rapidly expanding
      as our understanding of these transporters groups. Therefore, determining the
      interaction of membrane transporters with small molecule anticancer drugs can be
      facilitate the development of effective and safe treatment.

PMID- 21194403
TI  - Mechanisms of bacterial resistance to antibiotics in infections of COPD patients.
AB  - A key characteristic of airway inflammation in chronic obstructive pulmonary
      disease (COPD) is the persistent presence of bacteria in the lower airways. The
      most commonly isolated bacteria in the lower respiratory tract of COPD patients
      are nontypeable Haemophilus influenzae, Moraxella catarrhalis and Streptococcus
      pneumoniae, with growing evidence of the significance of Pseudomonas aeruginosa
      infections in severe COPD disease. This review focuses on the antibiotic
      resistant mechanisms associated with the gram-negative bacteria H. influenzae and
      M. catarrhalis and comparison with P. aeruginosa infection because of the recent
      evidence of its significance in patients with severe COPD disease. These
      mechanisms of resistance to beta-lactams in H. influenzae and M. catarrhalis are
      mostly associated with serine beta-lactamases of class A type, whereas P.
      aeruginosa strains exhibit a much broader repertoire with class A-D type
      mechanisms. Other mechanisms of antibiotic resistance include membrane
      permeability, efflux pump systems and mutations in antimicrobial targets.
      Antimicrobial resistance within biofilm matrices appears to be different to the
      mechanisms observed when the bacteria are in the planktonic state. P. aeruginosa
      exhibits a more numerous and diverse range of antimicrobial resistance mechanisms
      in comparison to M. catarrhalis and H. influenzae. The recognition that P.
      aeruginosa is associated with exacerbations in patients with more severe COPD and
      that turnover in infecting strains is detected (unlike in cystic fibrosis
      patients), then further investigation is required to better understand the
      contribution of antimicrobial resistance and other virulence mechanisms to poor
      clinical outcomes to improve therapeutic approaches.

PMID- 21194402
TI  - Pharmacogenetics of drug metabolizing enzymes and transporters: effects on
      pharmacokinetics and pharmacodynamics of anticancer agents.
AB  - There is wide interpatient variability in drug response and toxicity to standard
      doses of most anticancer medications. Genetic polymorphisms in genes encoding
      metabolic enzymes, receptors and drug transporters targeted by anticancer
      medications are often found, in part, to be responsible for the observed
      variability. Approximately 80% of all sequence variations residing in genes is in
      the form of single nucleotide polymorphisms or SNPs. The location of SNPs can be
      in the protein coding sequence, regulatory regions or at exon-intron boundaries
      of genes. Adverse drug reactions resulting from these sequence variations are due
      to changes in the activity of the encoded protein (in many instances the protein
      is non-functional) or perturbations in the level of gene expression. The goal of
      pharmacogenetic testing is to identify genetic polymorphisms that predispose
      patients to an adverse drug reaction, thereby allowing the health care provider
      to make informed decisions pertaining to the type of drug, dosage and dosage
      scheduling to be administered.

PMID- 21194404
TI  - Pathophysiology of airway colonization in critically ill COPD patient.
AB  - Although noninvasive ventilation (NIV) use in severe acute exacerbation of COPD
      has substantially reduced the need for intubation, an important number of COPD
      patients still are mechanically ventilated through a tracheal tube in the ICU.
      Intubation is a major risk factor for lower respiratory tract colonization (LRTC)
      in ICU patients. Other risk factors for LRTC include colonization of the oral
      cavity, nasopharynx, and gastric content. Aspiration of contaminated
      oropharyngeal secretions is increased by supine position, underinflation of
      tracheal cuff, coma, and sedation. Tracheal tube biofilm formation plays an
      important role as a reservoir for microorganisms. Reduced cough reflex, altered
      mucocilliary clearance, hypersecretion and retention of mucus are frequent in
      COPD patients. In addition, malnutrition and corticosteroid use are common in
      this population resulting in altered cellular, and humoral immunity and higher
      risk for LRTC. Incidence of LRTC varies from 22-95% of intubated patients.
      Pseudomonas aeruginosa is the most frequently isolated microorganism at day 3
      after intubation in COPD patients. LRTC is a major risk factor for ventilator
      associated pneumonia, which is associated with increased mortality and morbidity
      in ICU patients. Several measures could be suggested to reduce LRTC in critically
      ill COPD patients. NIV use in severe acute exacerbations reduces the need for
      intubation. In addition, the early use of NIV averts respiratory failure after
      extubation and could reduce the duration of invasive mechanical ventilation.
      Other measures might be efficient in preventing LRTC such as semirecumbent
      position, avoidance of gastric distension, polyurethane-cuffed tracheal tubes,
      silver-coated tracheal tubes, subglottic aspiration, and continuous control of
      cuff pressure. Further studies should determine the impact of preventive measures
      aiming at preventing LRTC on outcome of COPD patients requiring intubation and
      mechanical ventilation in the ICU.

PMID- 21194405
TI  - Pulmonary hypertension in COPD: pathophysiology and therapeutic targets.
AB  - The incidence of mild to moderate pulmonary hypertension (PH) is highly
      prevalent, reaching to 50% in advanced chronic obstructive pulmonary disease
      (COPD). However, a subpopulation (1-4% in most studies) with grim prognosis
      despite moderate airflow limitation, present with "out-of-proportion" severe PH,
      is arbitrarily defined by a mean PH >= 40 mmHg, at rest. The sequence of changes
      that lead to PH in COPD begins at early disease stages by the impairment of
      endothelial function, which is associated with impaired release of endothelium
      derived vasodilating (nitric oxide, prostacyclin) and vasoconstrictive agents
      (endothelin-1) and imbalance among them. PH in COPD is caused by vasoconstriction
      and remodelling of pulmonary arteries, which is characterized by the intimal
      proliferation of poorly differentiated smooth muscle cells and the deposition of
      elastic and collagen fibres. Hypoxia, inflammation and toxic effects of cigarette
      smoke, independently or additively interacting, are confirmed factors leading to
      PH. To date, long-term supplemental oxygen remains the primary treatment in COPD
      patients with PH. The administration of new vasodilators (prostanoids, endothelin
      1 receptor antagonists and phosphodiesterase-5 inhibitors) dedicated to
      idiopathic pulmonary arterial hypertension in the disproportionate subgroup of
      patients with "out-of-proportion" PH may be considered in the setting of clinical
      trials. The use of these drugs in COPD patients with PH < 40 mmHg may worsen gas
      exchange, and to date, has no proven benefit. Future treatments must target more
      directly pathogenetic mechanisms. Therefore, novel agents have been proposed and
      are under active investigation, including 5-HT receptor antagonists, Rho-kinase
      inhibitors, statins and stem cell therapy.

PMID- 21194406
TI  - Immunologic impact of nutrient depletion in chronic obstructive pulmonary
      disease.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by small airways,
      alveolar and systemic inflammation and remodeling causing airflow limitation and
      parenchymal destruction. Mechanisms of oxidative stress include exposure to
      cigarette smoke and environmental stimuli that activate proinflammatory
      responses, stimulate alveolar neutrophils and macrophages and lead to apoptosis
      of endothelial and epithelial cells. COPD may have origins in fetal and neonatal
      factors that affect intrauterine growth of lungs and airways, lead to low birth
      weight and impair the development of immune response. Maternal smoking may
      diminish interferon response secondary to micronutrient deficiency, particularly
      of Vitamin A, and support persistence of Respiratory Syncytial Virus (RSV),
      normally a childhood pathogen, into adult life. Muscle wasting and cachexia are
      systemic features of COPD. Cachexia is associated with systemic inflammation and
      worsened by Vitamin D deficiency. Nutritional depletion is related to poor
      survival and is a rational target for therapeutic intervention in advanced and
      critically ill patients. Preliminary studies and suggest that supplementation
      with omega-3 polyunsaturated fatty acids and micronutrient repletion with Vitamin
      A, Vitamin D3, and zinc may have beneficial effects in COPD.

PMID- 21194407
TI  - Respiratory muscle dysfunction in COPD: from muscles to cell.
AB  - Respiratory muscle dysfunction is a cardinal feature of acute and chronic
      respiratory failure in COPD. Diaphragm and accessory inspiratory muscles face
      increased load due to increased lung resistance and elastance, as well as
      increased ventilatory demands. Concomitantly, the capacity of the inspiratory
      muscles to generate pressure is decreased due to mechanical disadvantage imposed
      by hyperinflation. Additionally, inflammation and oxidative stress impair muscle
      fiber specific force generation and increase diaphragm susceptibility to sarcomer
      disruption during acute inspiratory loading. In response to this increased load
      diaphragm presents unique adaptations in its cellular structure and passive and
      contractile mechanical properties, and displays a more efficient metabolic
      armamentarium. A shift of muscle fiber type towards slow-twitch, oxidative type I
      fibers, which are more fatigue-resistant, increases diaphragmatic endurance but
      protein degradation and a significant reduction in myosin content decrease its
      force generating capacity. Furthermore, diaphragm adapts to chronic
      hyperinflation by sarcomere deletion so that its overall length is shortened, in
      an attempt to preserve optimum force-length relationship. Adaptation however may
      not be complete, or may be overwhelmed by pathophysiologic derangements during
      exercise or acute exacerbations, leading to obvious "dysfunction" of the
      respiratory muscles, and if sustained, ultimately to muscle fatigue and
      respiratory pump failure.

PMID- 21194408
TI  - Oxidative stress in patients with COPD.
AB  - The lung is the organ with the highest exposure to ambient air in the entire
      human architecture. Due to its large surface area and blood supply, the lung is
      susceptible to oxidative injury in the form of myriads of reactive oxygen species
      (ROS) and free radicals. In order to provide defense against the oxidative
      burden, the lungs produce various endogenous agents called antioxidants. The
      antioxidant species help the lungs ward off the deleterious consequences of a
      wide variety of oxidants/ROS, either of endogenous or environmental origin.
      Several mechanisms are related to the potential connection between COPD and
      oxidative stress. One of the most important actions of the oxidative stress is
      the influence of the molecular mechanisms involved in the expression
      proinflammatory genes. There is plenty of evidence supporting an imbalance
      between oxidants and antioxidants in the lung and systemic circulation of smokers
      and COPD patients. Detection of the oxidative burden and evaluation of their
      progression and phenotypes by oxidative stress biomarkers have proven challenging
      and difficult. Both invasive and non-invasive techniques have provided different
      biomarkers which contribute to the oxidative burden of the airways. An effective
      wide-spectrum antioxidant therapy with bioavailability is urgently needed to
      control the local and systemic oxidative burst in COPD. In that direction,
      several antioxidant agents have been evaluated as potential candidates for the
      management of COPD. However, despite some encouraging results, clinical trials so
      far have failed to elaborately define the type of antioxidant, the regimen and
      the time period of treatment that may improve clinically meaningful outcomes in
      patients with COPD.

PMID- 21194409
TI  - Mechanisms of altered cell immunity and cytotoxicity in COPD.
AB  - The lungs of smokers are exposed to the toxic substances of cigarette smoke, but
      only 10-20% of them will develop chronic obstructive pulmonary disease (COPD).
      For COPD to develop, cigarette smoke has to bypass or overwhelm the host front
      lines of defence, i.e. the respiratory tract mucosal epithelium, which serves as
      an effective physical barrier and the innate immune system, which provides an
      immediate, yet non-specific response. In this review, we will describe briefly
      how cigarette smoke succeeds in damaging the physical barrier of mucosal
      epithelium and the innate immune system, and how it induces effector mechanisms
      of the adaptive immune system, which are particularly cytotoxic to the host. We
      will also discuss the role of other stimuli with immunogenic potential, such of
      the role of pathogens which colonize or evade the lungs of COPD patients and of
      self tissue antigens, which may lead to autoimmune disease when there is chronic
      inflammation. Although the primary mechanism(s) of undesirable innate and
      adaptive immune responses in COPD are still a matter of debate, it is currently
      accepted that they are the root cause of COPD.

PMID- 21194410
TI  - Current drug targets for the critically ill COPD patient.

PMID- 21194411
TI  - Recent patents concerning targeted therapy of apoptosis resistance in pancreatic
      cancer.
AB  - Pancreatic cancer is one of the most malignant forms of cancer. Due to numerous
      defects of the apoptosis machinery this tumor shows a high resistance towards
      conventional oncological therapies. On the level of the extrinsic pathway, signal
      transduction is flawed by over-expression of decoy receptors but also by a
      dysfunctional death inducing signaling complex (DISC). The mitochondrial pathway,
      normally stimulated by cell stress and toxic agents is impeded by over-expression
      of anti-apoptotic members of the Bcl 2 protein family and the so-called inhibitor
      of apoptosis proteins (IAPs). To overcome the dysfunction of the apoptosis
      pathway, new therapeutics focus on molecular targets within the apoptosis
      pathway. Recently, many new treatment modalities have been reported like
      recombinant ligands of the cell death receptors or inhibitors of anti-apoptotic
      Bcl-2 members. Furthermore, various substances for the direct activation of the
      caspase cascade were patented and the over-expression of IAPs could be treated by
      binding inhibitors or using RNA interference techniques. The present review aims
      at giving an overview on these new treatment modalities.

PMID- 21194412
TI  - Becoming a global citizen through nursing education: lessons learned in
      developing evaluation tools.
AB  - While global health practica are being increasingly described in nursing
      education literature, course evaluation of same receives comparatively less
      attention. In this article, authors report on an evaluation project, undertaken
      to rigorously examine the existing evaluation methods for an elective global
      health practicum with placements in India and northern Canada. Sixteen students
      were interviewed and course evaluation tools were reviewed. Resulting themes
      include students' sense of preparedness, the centrality of the student-preceptor
      relationship, the importance of supported self-reflection, and the usefulness of
      evaluation methods. Participants viewed existing course evaluation methods as
      generally useful, therefore requiring only minor adjustments. There were also
      structural revisions to the preparation, placement, and post-placement phases of
      the course and broader lessons learned. Lessons include the importance of
      critical social perspectives and the value of past students revisiting their
      experiences in such a way as make conscious connections between placement
      experiences and their current professional practice.

PMID- 21194413
TI  - Leveraging differences for collaborative advantage: enhancing student learning
      through an international educational collaboration.
AB  - This case study in collaboration development describes the relationship from
      initiation through maintenance over three years between a high profile research
      focused school of nursing in the U.S. and a school in the UK known for learning
      and teaching innovation. The ultimate goal of the collaboration is to enhance
      nursing student learning opportunities to best prepare students to function in
      the complex and ever-changing world of nursing practice. This goal has been, and
      continues to be, achieved through implementation of innovative teaching and
      learning strategies including the use of high fidelity simulation. The authors
      describe the intellectual collaborative advantage that the relationship between
      the schools has made possible as well as key principles to be considered when any
      organization is contemplating a collaboration.

PMID- 21194414
TI  - Including probe-level measurement error in robust mixture clustering of
      replicated microarray gene expression.
AB  - Probabilistic mixture models provide a popular approach to cluster noisy gene
      expression data for exploring gene function. Since gene expression data obtained
      from microarray experiments are often associated with significant sources of
      technical and biological noise, replicated experiments are typically used to deal
      with data variability, and internal replication (e.g. from multiple probes per
      gene in an experiment) provides valuable information about technical sources of
      noise. However, current implementations of mixture models either do not consider
      the correlation between the replicated measurements for the same experimental
      condition, or ignore the probe-level measurement error, and thus overlook the
      rich information about technical noise. Moreover, most current methods use non
      robust Gaussian components to describe the data, and these methods are therefore
      sensitive to non-Gaussian clusters and outliers. In many cases, this will lead to
      over-estimation of the number of model components as multiple Gaussian components
      are used to fit a non-Gaussian cluster. We propose a robust Student's t-mixture
      model, which explicitly handles replicated gene expression data, includes the
      consideration of probe-level measurement error when available and automatically
      selects the appropriate number of model components using a minimum message length
      criterion. We apply the model to gene expression data using probe-level
      measurements from an Affymetrix probe-level model, multi-mgMOS, which provides
      uncertainty estimates. The proposed Student's t-mixture model shows robust
      performance on synthetic data sets with realistic noise characteristics in
      comparison to a standard Gaussian mixture model and two other previously
      published methods. We also compare performance with these methods on two yeast
      time-course data sets and show that the new method obtains more biologically
      meaningful clusters in terms of enrichment statistics for GO categories and
      interactions between transcription factors and genes. Automatically selecting the
      number of components is more computationally efficient than using a model
      selection approach and allows the methods to be applied to larger data sets.

PMID- 21194415
TI  - Relationship of tooth loss to mild memory impairment and cognitive impairment:
      findings from the Fujiwara-kyo study.
AB  - BACKGROUND: This cross-sectional study investigated the relationship between the
      number of remaining teeth to mild memory impairment (MMI), which is a preclinical
      stage of dementia, and to cognitive impairment. METHODS: The subjects were aged
      65 years or older and were grouped according to their score for the Mini-Mental
      State Examination (MMSE), the three-word delayed recall test in the MMSE, and the
      Geriatric Depression Scale into the control group (n = 3,696), the MMI group (n =
      121), and the low MMSE score (23 or lower) group (n = 214). We collected data on
      the number of remaining teeth, the length of the edentulous period, health
      related lifestyle, medical history, blood pressure, height, and body weight.
      Fasting venous blood samples were also obtained. RESULTS: Multiple logistic
      regression analysis, adjusted for depressive symptoms, age, sex, length of
      education, and other explanatory variables, revealed that the odds ratios of 0-10
      remaining teeth to 22-32 remaining teeth were 1.679 (95% CI 1.073-2.627) for MMI
      and 2.177 (95% CI 1.510-3.140) for a low MMSE score. A significant relationship
      was also found between the length of the edentulous period and the risk of a low
      MMSE score (odds ratio 3.102, 95% CI 1.432-6.720) (15 years or more/less than 15
      years). CONCLUSIONS: Our findings suggest that tooth loss is associated with
      cognitive function.

PMID- 21194416
TI  - Comparison of imputation methods for handling missing covariate data when fitting
      a Cox proportional hazards model: a resampling study.
AB  - BACKGROUND: The appropriate handling of missing covariate data in prognostic
      modelling studies is yet to be conclusively determined. A resampling study was
      performed to investigate the effects of different missing data methods on the
      performance of a prognostic model. METHODS: Observed data for 1000 cases were
      sampled with replacement from a large complete dataset of 7507 patients to obtain
      500 replications. Five levels of missingness (ranging from 5% to 75%) were
      imposed on three covariates using a missing at random (MAR) mechanism. Five
      missing data methods were applied; a) complete case analysis (CC) b) single
      imputation using regression switching with predictive mean matching (SI), c)
      multiple imputation using regression switching imputation, d) multiple imputation
      using regression switching with predictive mean matching (MICE-PMM) and e)
      multiple imputation using flexible additive imputation models. A Cox proportional
      hazards model was fitted to each dataset and estimates for the regression
      coefficients and model performance measures obtained. RESULTS: CC produced biased
      regression coefficient estimates and inflated standard errors (SEs) with 25% or
      more missingness. The underestimated SE after SI resulted in poor coverage with
      25% or more missingness. Of the MI approaches investigated, MI using MICE-PMM
      produced the least biased estimates and better model performance measures.
      However, this MI approach still produced biased regression coefficient estimates
      with 75% missingness. CONCLUSIONS: Very few differences were seen between the
      results from all missing data approaches with 5% missingness. However, performing
      MI using MICE-PMM may be the preferred missing data approach for handling between
      10% and 50% MAR missingness.

PMID- 21194417
TI  - Increasing health worker capacity through distance learning: a comprehensive
      review of programmes in Tanzania.
AB  - BACKGROUND: Tanzania, like many developing countries, faces a crisis in human
      resources for health. The government has looked for ways to increase the number
      and skills of health workers, including using distance learning in their
      training. In 2008, the authors reviewed and assessed the country's current
      distance learning programmes for health care workers, as well as those in
      countries with similar human resource challenges, to determine the feasibility of
      distance learning to meet the need of an increased and more skilled health
      workforce. METHODS: Data were collected from 25 distance learning programmes at
      health training institutions, universities, and non-governmental organizations
      throughout the country from May to August 2008. Methods included internet
      research; desk review; telephone, email and mail-in surveys; on-site
      observations; interviews with programme managers, instructors, students,
      information technology specialists, preceptors, health care workers and Ministry
      of Health and Social Welfare representatives; and a focus group with national
      HIV/AIDS care and treatment organizations. RESULTS: Challenges include lack of
      guidelines for administrators, instructors and preceptors of distance learning
      programmes regarding roles and responsibilities; absence of competencies for
      clinical components of curricula; and technological constraints such as lack of
      access to computers and to the internet. Insufficient funding resulted in
      personnel shortages, lack of appropriate training for personnel, and lack of
      materials for students.Nonetheless, current and prospective students expressed
      overwhelming enthusiasm for scale-up of distance learning because of the unique
      financial and social benefits offered by these programs. Participants were
      retained as employees in their health care facilities, and remained in their
      communities and supported their families while advancing their careers. Space in
      health training institutions was freed up for new students entering in-residence
      pre-service training. CONCLUSIONS: A blended print-based distance learning model
      is most feasible at the national level due to current resource and infrastructure
      constraints. With an increase in staffing; improvement of infrastructure,
      coordination and curricula; and decentralization to the zonal or district level,
      distance learning can be an effective method to increase both the skills and the
      numbers of qualified health care workers capable of meeting the health care needs
      of the Tanzanian population.

PMID- 21194418
TI  - The Renilla luciferase gene as a reference gene for normalization of gene
      expression in transiently transfected cells.
AB  - BACKGROUND: The importance of appropriate normalization controls in quantitative
      real-time polymerase chain reaction (qPCR) experiments has become more apparent
      as the number of biological studies using this methodology has increased. In
      developing a system to study gene expression from transiently transfected
      plasmids, it became clear that normalization using chromosomally encoded genes is
      not ideal, at it does not take into account the transfection efficiency and the
      significantly lower expression levels of the plasmids. We have developed and
      validated a normalization method for qPCR using a co-transfected plasmid.
      RESULTS: The best chromosomal gene for normalization in the presence of the
      transcriptional activators used in this study, cadmium, dexamethasone, forskolin
      and phorbol-12-myristate 13-acetate was first identified. qPCR data was analyzed
      using geNorm, Normfinder and BestKeeper. Each software application was found to
      rank the normalization controls differently with no clear correlation. Including
      a co-transfected plasmid encoding the Renilla luciferase gene (Rluc) in this
      analysis showed that its calculated stability was not as good as the optimised
      chromosomal genes, most likely as a result of the lower expression levels and
      transfection variability. Finally, we validated these analyses by testing two
      chromosomal genes (B2M and ActB) and a co-transfected gene (Rluc) under
      biological conditions. When analyzing co-transfected plasmids, Rluc normalization
      gave the smallest errors compared to the chromosomal reference genes.
      CONCLUSIONS: Our data demonstrates that transfected Rluc is the most appropriate
      normalization reference gene for transient transfection qPCR analysis; it
      significantly reduces the standard deviation within biological experiments as it
      takes into account the transfection efficiencies and has easily controllable
      expression levels. This improves reproducibility, data validity and most
      importantly, enables accurate interpretation of qPCR data.

PMID- 21194419
TI  - Trial design: Computer guided normal-low versus normal-high potassium control in
      critically ill patients: Rationale of the GRIP-COMPASS study.
AB  - BACKGROUND: Potassium depletion is common in hospitalized patients and can cause
      serious complications such as cardiac arrhythmias. In the intensive care unit
      (ICU) the majority of patients require potassium suppletion. However, there are
      no data regarding the optimal control target in critically ill patients. After
      open-heart surgery, patients have a strongly increased risk of atrial
      fibrillation or atrial flutter (AFF). In a novel trial design, we examined if in
      these patients different potassium control-targets within the normal range may
      have different effects on the incidence of AFF. METHODS/DESIGN: The "computer
      driven Glucose and potassium Regulation program in Intensive care Patients with
      COMparison of PotASSium targets within normokalemic range (GRIP-COMPASS) trial"
      is a single-center prospective trial in which a total of 1200 patients are
      assigned to either a potassium control-target of 4.0 mmol/L or 4.5 mmol/L in
      consecutive alternating blocks of 50 patients each. Potassium levels are
      regulated by the computer-assisted potassium suppletion algorithm called GRIP-II
      (Glucose and potassium regulation for Intensive care Patients). Primary endpoint
      is the in-hospital incidence of AFF after cardiac surgery. Secondary endpoints
      are: in-hospital AFF in medical patients or patients after non-cardiac surgery,
      actually achieved potassium levels and their variation, electrolyte and glucose
      levels, potassium and insulin requirements, cumulative fluid balance, (ICU)
      length of stay, ICU mortality, hospital mortality and 90-day mortality.
      DISCUSSION: The GRIP-COMPASS trial is the first controlled clinical trial to date
      that compares potassium targets. Other novel methodological elements of the study
      are that it is performed in ICU patients where both targets are within the normal
      range and that a computer-assisted potassium suppletion algorithm is used. TRIAL
      REGISTRATION: NCT 01085071 at ClinicalTrials.gov.

PMID- 21194420
TI  - The chromosomal association/dissociation of the chromatin insulator protein Cp190
      of Drosophila melanogaster is mediated by the BTB/POZ domain and two acidic
      regions.
AB  - BACKGROUND: Chromatin insulators or boundary elements are a class of functional
      elements in the eukaryotic genome. They regulate gene transcription by
      interfering with promoter-enhancer communication. The Cp190 protein of Drosophila
      melanogaster is essential to the function of at least three-types of chromatin
      insulator complexes organized by Su(Hw), CTCF and BEAF32. RESULTS: We mapped
      functional regions of Cp190 in vivo and identified three domains that are
      essential for the insulator function and for the viability of flies: the BTB/POZ
      domain, an aspartic acid-rich (D-rich) region and a C-terminal glutamic acid-rich
      (E-rich) region. Other domains including the centrosomal targeting domain and the
      zinc fingers are dispensable. The N-terminal CP190BTB-D fragment containing the
      BTB/POZ domain and the D-rich region is sufficient to mediate association with
      all three types of insulator complexes. The fragment however is not sufficient
      for insulator activity or viability. The Cp190 and CP190BTB-D are regulated
      differently in cells treated with heat-shock. The Cp190 dissociated from
      chromosomes during heat-shock, indicating that dissociation of Cp190 with
      chromosomes can be regulated. In contrast, the CP190BTB-D fragment didn't
      dissociate from chromosomes in the same heat-shocked condition, suggesting that
      the deleted C-terminal regions have a role in regulating the dissociation of
      Cp190 with chromosomes. CONCLUSIONS: The N-terminal fragment of Cp190 containing
      the BTB/POZ domain and the D-rich region mediates association of Cp190 with all
      three types of insulator complexes and that the E-rich region of Cp190 is
      required for dissociation of Cp190 from chromosomes during heat-shock. The heat
      shock-induced dissociation is strong evidence indicating that dissociation of the
      essential insulator protein Cp190 from chromosomes is regulated. Our results
      provide a mechanism through which activities of an insulator can be modulated by
      internal and external cues.

PMID- 21194421
TI  - Blood lipids and adipokines concentrations during a 6-month nutritional and
      physical activity intervention for metabolic syndrome treatment.
AB  - BACKGROUND: To report changes in body weight, total and central fat mass,
      metabolic, hormonal and inflammatory parameters in overweight people who
      participated in a six months weight loss intervention associating diet management
      and exercise. SUBJECTS AND METHODS: Fourteen subjects (10 M, 4 F, mean age 62.9
      +/- 6.9 years, BMI 30.4+/- 3.8 kg/m2) presenting the characteristics of the
      Metabolic Syndrome (MS) were included in the survey. They followed a three weeks
      (D0 to D20) cure in a medical establishment and a six months (D20 to M3 and M6)
      follow up at home. During the cure, they receive a balanced diet corresponding to
      500 Kcal deficit vs their daily energy expenditure (DEE) and they exercised 2 to
      3 hours per day.At D0, D20, M3 and M6, body composition (lean mass, total and
      central fat mass) was analyzed with DEXA, blood pressure was taken and blood was
      collected to evaluate glycaemia, triglycerides, total, LDL and HDL cholesterol,
      insulin, leptin and adiponectin levels, CRP and pro-inflammatory interleukines
      IL1, IL.6 and TNFalpha. RESULTS: All parameters listed above except the cytokine
      were improved at D20, so that 4 subjects among 14 still presented the MS. After
      returning to home, these parameters remained stable. CONCLUSION: The efficacy of
      therapeutic lifestyle modifications with education and exercise and diet was
      demonstrated, but the compliance to the new healthy lifestyle initiated during
      the cure was not optimal.

PMID- 21194422
TI  - An open randomized clinical trial in comparing two artesunate-based combination
      treatments on Plasmodium falciparum malaria in Nigerian children:
      artesunate/sulphamethoxypyrazine/pyrimethamine (fixed dose over 24 hours) versus
      artesunate/amodiaquine (fixed dose over 48 hours).
AB  - BACKGROUND: Several studies have demonstrated the efficacy of artemisinin
      combination therapy (ACT) across malaria zones of the world. Fixed dose ACT with
      shorter courses and fewer tablets may be key determinants to ease of
      administration and compliance. METHODS: Children aged one year to 13 years
      presenting with uncomplicated Plasmodium falciparum malaria were recruited in
      Ibadan, south-western Nigeria. A total of 250 children each were randomly
      assigned to receive three doses of artesunate/sulphamethoxypyrazine/pyrimethamine
      (AS + SMP) (12 hourly doses over 24 hours) or three doses of
      artesunate/amodiaquine (AS + AQ) (daily doses over 48 hours). Efficacy and safety
      of the two drugs were assessed using a 28-day follow-up and the primary outcome
      was PCR- corrected parasitological cure rate and clinical response. RESULTS:
      There were two (0.4%) early treatment failures, one in each treatment arm. The
      PCR corrected cure rates for day 28 was 97.9% in the AS + AQ arm and 95.6% in the
      AS + SMP arm (p = 0.15). The re-infection rate was 1.7% in the AS + AQ arm and
      5.7% in the AS + SMP arm (p = 0.021). The fever clearance time was similar in the
      two treatment groups: 1 - 2 days for both AS + SMP and AS + AQ (p = 0.271). The
      parasite clearance time was also similar in the two treatment groups with 1 - 7
      days for AS + SMP and 1 - 4 days for AS + AQ (p = 0.941). The proportion of
      children with gametocytes over the follow-up period was similar in both treatment
      groups. Serious Adverse Events were not reported in any of the patients and in
      all children, laboratory values (packed cell volume, liver enzymes, bilirubin)
      remained within normal levels during the follow-up period but the packed cell
      volume was significantly lower in the AS + SMP group. CONCLUSIONS: This study
      demonstrates that AS + SMP FDC given as three doses over 24 hours (12-hour
      intervals) has similar efficacy as AS + AQ FDC given as three doses over 48 hours
      (24-hour interval) for the treatment of uncomplicated Plasmodium falciparum
      malaria in children in Nigeria. Both drugs also proved to be safe. Therefore, AS
      + SMP could be an alternative to currently recommended first-line ACT with
      continuous resistance surveillance.

PMID- 21194423
TI  - Serum albumin and mortality risk in a hyperendemic area of HCV infection in
      Japan.
AB  - BACKGROUND: Hypoalbuminemia has been shown to be associated with increased
      mortality. We reported a mass screening in 1990 of X town in Japan, which
      demonstrated a high prevalence of hepatitis C virus (HCV) infection. This follow
      up study determined, through a period of 12 years, whether serum albumin levels
      impact on the life prognosis of the residents of X town. RESULTS: Of the 509
      subjects, 69 had died and 55 had moved to other regions by 2002. Therefore, we
      analyzed 454 people for whom we could confirm life and death between 1990 and
      2002. Albumin levels were assigned to two groups, low (<4.0 g/L, group A) and
      normal (>=4.0 g/L, group B). Of the 454 subjects analyzed, 25 were in group A and
      429 in group B and the mortality was 68.0% (17/25 cases, P < 0.00001 vs. group B)
      and 12.1% (52/429), respectively. Mortality from hepatocellular carcinoma (HCC)
      was 66.7% in group A (6/9 cases, P = 0.01 vs. group B) and 15.8% (3/19) in group
      B. According to multivariate analysis, five factors--50 years or older, low
      albumin level (<4.0 g/L), abnormal AST level, history of smoking, and absence of
      alcohol consumption--were associated with death. The adjusted odds ratios for
      these five factors were 20.65, 10.79, 2.58, 2.24 and 2.08, respectively, and each
      was statistically significant. CONCLUSIONS: We show that the serum albumin level
      is an independent risk factor for mortality from all causes in the residents of X
      town and an important prognostic indicator. Improvement of hypoalbuminaemia
      should be considered for improvement of prognosis.

PMID- 21194424
TI  - Hepatic accumulation of intestinal cholesterol is decreased and fecal cholesterol
      excretion is increased in mice fed a high-fat diet supplemented with milk
      phospholipids.
AB  - BACKGROUND: Milk phospholipids (PLs) reduce liver lipid levels when given as a
      dietary supplement to mice fed a high-fat diet. We have speculated that this
      might be due to reduced intestinal cholesterol uptake. METHODS: Mice were given a
      high-fat diet for 3 or 5 weeks that had no added PL or that were supplemented
      with 1.2% by wt PL from cow's milk. Two milk PL preparations were investigated:
      a) a PL-rich dairy milk extract (PLRDME), and b) a commercially-available milk PL
      concentrate (PC-700). Intestinal cholesterol uptake was assessed by measuring
      fecal and hepatic radioactivity after intragastric administration of
      [14C]cholesterol and [3H]sitostanol. Fecal and hepatic lipids were measured
      enzymatically and by ESI-MS/MS. RESULTS: Both PL preparations led to significant
      decreases in total liver cholesterol and triglyceride (-20% to -60%, P < 0.05).
      Hepatic accumulation of intragastrically-administered [14C]cholesterol was
      significantly less (-30% to -60%, P < 0.05) and fecal excretion of
      [14C]cholesterol and unlabeled cholesterol was significantly higher in PL
      supplemented mice (+15% to +30%, P < 0.05). Liver cholesterol and triglyceride
      levels were positively correlated with hepatic accumulation of intragastrically
      administered [14C]cholesterol (P < 0.001) and negatively correlated with fecal
      excretion of [14C]cholesterol (P < 0.05). Increased PL and ceramide levels in the
      diet of mice supplemented with milk PL were associated with significantly higher
      levels of fecal PL and ceramide excretion, but reduced levels of hepatic PL and
      ceramide, specifically, phosphatidylcholine (-21%, P < 0.05) and
      monohexosylceramide (-33%, P < 0.01). CONCLUSION: These results indicate that
      milk PL extracts reduce hepatic accumulation of intestinal cholesterol and
      increase fecal cholesterol excretion when given to mice fed a high-fat diet.

PMID- 21194425
TI  - Kinin B1 receptors mediate depression-like behavior response in stressed mice
      treated with systemic E. coli lipopolysaccharide.
AB  - BACKGROUND: Kinin B1 receptors are inducible molecules up-regulated after
      inflammatory stimuli. This study evaluated the relevance of kinin B1 receptors in
      a mouse depression behavior model. METHODS: Mice were exposed to a 5-min swimming
      session, and 30 min later they were injected with E. coli lipopolysaccharide
      (LPS). Depression-like behavior was assessed by determining immobility time in a
      tail suspension test. Different brain structures were collected for molecular and
      immunohistochemical studies. Anhedonia was assessed by means of a sucrose intake
      test. RESULTS: Our protocol elicited an increase in depression-like behavior in
      CF1 mice, as assessed by the tail-suspension test, at 24 h. This behavior was
      significantly reduced by treatment with the selective B1 receptor antagonists R
      715 and SSR240612. Administration of SSR240612 also prevented an increase in
      number of activated microglial cells in mouse hippocampus, but did not affect a
      reduction in expression of mRNA for brain-derived neurotrophic factor. The
      increased immobility time following LPS treatment was preceded by an enhancement
      of hippocampal and cortical B1 receptor mRNA expression (which were maximal at 1
      h), and a marked production of TNFalpha in serum, brain and cerebrospinal fluid
      (between 1 and 6 h). The depression-like behavior was virtually abolished in
      TNFalpha p55 receptor-knockout mice, and increased B1 receptor mRNA expression
      was completely absent in this mouse strain. Furthermore, treatment with SSR240612
      was also effective in preventing anhedonia in LPS-treated mice, as assessed using
      a sucrose preference test. CONCLUSION: Our data show, for the first time,
      involvement of kinin B1 receptors in depressive behavioral responses, in a
      process likely associated with microglial activation and TNFalpha production.
      Thus, selective and orally active B1 receptor antagonists might well represent
      promising pharmacological tools for depression therapy.

PMID- 21194426
TI  - The long-term benefit of computer-assisted surgical navigation in
      unicompartmental knee arthroplasty.
AB  - We reviewed the outcomes of 30 consecutive primary unicompartmental knee
      arthroplasties (UKA) performed by a single surgeon for medial compartmental
      osteoarthritis. Fifteen Allegretto knees were implanted without computer
      navigation and 15 EIUS knees were implanted with navigation. We compared the
      survivorship, radiological and clinical outcomes of the two groups at an average
      of 8.9 years and 6.9 years respectively. The patients were assessed clinically
      using the Oxford Knee Score (OKS) and radiologically using long-leg weightbearing
      films and non-weightbearing computed tomography alignment measurements. The
      overall survivorship was 86.7% at 9 years. A higher proportion of navigated knees
      were well aligned with a more reproducible position and malaligned knees tended
      to have a less favourable OKS. However, we found no statistically significant
      difference in survivorship, clinical outcome and radiological alignment between
      the two groups.

PMID- 21194427
TI  - Descriptive epidemiology of screen and non-screen sedentary time in adolescents:
      a cross sectional study.
AB  - BACKGROUND: Much attention has been paid to adolescents' screen time, however
      very few studies have examined non-screen sedentary time (NSST). This study aimed
      to (1) describe the magnitude and composition of screen sedentary time (SST) and
      NSST in Australian adolescents, (2) describe the socio-demographic correlates of
      SST and NSST, and (3) determine whether screen time is an adequate surrogate for
      total sedentary behaviour in this population. METHODS: 2200 9-16 year old
      Australians provided detailed use of time data for four days. Non-screen
      sedentary time (NSST) included time spent participating in activities expected to
      elicit <3 METs whilst seated or lying down (other than sleeping), excluding
      screen-based activities (television, playing videogames or using computers).
      Total sedentary time was the sum of screen time and NSST. RESULTS: Adolescents
      spent a mean (SD) of 345 (105) minutes/day in NSST, which constituted 60% of
      total sedentary time. School activities contributed 42% of NSST, socialising 19%,
      self-care (mainly eating) 16%, and passive transport 15%. Screen time and NSST
      showed opposite patterns in relation to key socio-demographic characteristics,
      including sex, age, weight status, household income, parental education and day
      type. Because screen time was negatively correlated with NSST (r = -0.58), and
      exhibited a moderate correlation (r = 0.53) with total sedentary time, screen
      time was only a moderately effective surrogate for total sedentary time.
      CONCLUSIONS: To capture a complete picture of young people's sedentary time,
      studies should endeavour to measure both screen time and NSST.

PMID- 21194428
TI  - Public health: disconnections between policy, practice and research.
AB  - BACKGROUND: Public health includes policy, practice and research but to
      sufficiently connect academic research, practice and public health policy appears
      to be difficult. Collaboration between policy, practice and research is
      imperative to obtaining more solid evidence in public health. However, the three
      domains do not easily work together because they emanate from three more or less
      independent 'niches'.Work cycles of each niche have the same successive steps:
      problem recognition, approach formulation, implementation, and evaluation, but
      are differently worked out. So far, the research has focused on agenda-setting
      which belongs to the first step, as expressed by Kingdon, and on the use of
      academic knowledge in policy makers' decision-making processes which belongs to
      the fourth step, as elaborated by Weiss. In addition, there are more steps in the
      policy-making process where exchange is needed. METHOD: A qualitative descriptive
      research was conducted by literature search. We analyzed the four steps of the
      policy, practice and research work cycles. Next, we interpreted the main
      conflicting aspects as disconnections for each step. RESULTS: There are some
      conspicuous differences that strengthen the niche character of each domain and
      hamper integration and collaboration. Disconnections ranged from formulating
      priorities in problem statements to power roles, appraisal of evidence, work
      attitudes, work pace, transparency of goals, evaluation and continuation
      strategies and public accountability. Creating awareness of these disconnections
      may result in more compatibility between researchers, policy makers and
      practitioners. CONCLUSION: We provide an analysis that can be used by public
      health services-related researchers, practitioners and policy makers to be aware
      of the risk for disconnections. A synthesis of the social, practical and
      scientific relevance of public health problems should be the starting point for a
      dialogue that seeks to establish a joint approach. To overcome the above
      mentioned disconnections, face-to-face encounters consistently emerge as the most
      efficient way to transfer knowledge, achieve higher quality and acknowledge
      mutual dependence. We recommend practice and policy based research networks to
      establish strong links between researchers, policy makers and practitioners to
      improve public health.

PMID- 21194429
TI  - VEGF121b and VEGF165b are weakly angiogenic isoforms of VEGF-A.
AB  - BACKGROUND: Different isoforms of VEGF-A (mainly VEGF121, VEGF165 and VEGF189)
      have been shown to display particular angiogenic properties in the generation of
      a functional tumor vasculature. Recently, a novel class of VEGF-A isoforms,
      designated as VEGF(xxx)b, generated through alternative splicing, have been
      described. Previous studies have suggested that these isoforms may inhibit
      angiogenesis. In the present work we have produced recombinant VEGF121/165b
      proteins in the yeast Pichia pastoris and constructed vectors to overexpress
      these isoforms and assess their angiogenic potential. RESULTS: Recombinant
      VEGF121/165b proteins generated either in yeasts or mammalian cells activated
      VEGFR2 and its downstream effector ERK1/2, although to a lesser extent than
      VEGF165. Furthermore, treatment of endothelial cells with VEGF121/165b increased
      cell proliferation compared to untreated cells, although such stimulation was
      lower than that induced by VEGF165. Moreover, in vivo angiogenesis assays
      confirmed angiogenesis stimulation by VEGF121/165b isoforms. A549 and PC-3 cells
      overexpressing VEGF121b or VEGF165b (or carrying the PCDNA3.1 empty vector, as
      control) and xenotransplanted into nude mice showed increased tumor volume and
      angiogenesis compared to controls. To assess whether the VEGF(xxx)b isoforms are
      differentially expressed in tumors compared to healthy tissues,
      immunohistochemical analysis was conducted on a breast cancer tissue microarray.
      A significant increase (p < 0.05) in both VEGF(xxx)b and total VEGF-A protein
      expression in infiltrating ductal carcinomas compared to normal breasts was
      observed. A positive significant correlation (r = 0.404, p = 0.033) between
      VEGF(xxx)b and total VEGF-A was found. CONCLUSIONS: Our results demonstrate that
      VEGF121/165b are not anti-angiogenic, but weakly angiogenic isoforms of VEGF-A.
      In addition, VEGF(xxx)b isoforms are up-regulated in breast cancer in comparison
      with non malignant breast tissues. These results are to be taken into account
      when considering a possible use of VEGF121/165b-based therapies in patients.

PMID- 21194430
TI  - Video-assisted mediastinoscopic transhiatal esophagectomy combined with
      laparoscopy for esophageal cancer.
AB  - BACKGROUND: Minimally invasive transhiatal esophagectomy for esophageal cancer
      includes mediastinoscopic and laparoscopic transhiatal esophagectomy. It is
      inadequate in both two techniques. It is impossible to dissect the lower
      esophagus with single mediastinoscopy or the upper and middle esophagus with
      single laparoscopy. We use mediastinoscopy combined with laparoscopy to dissect
      the whole esophagus and stomach including lymph node dissection. In addition,
      laparoscopic gastric mobilization leads to less trauma than an open gastroplasty.
      METHODS: 40 cases of video-assisted mediastinoscopic transhiatal esophagectomy
      were performed and divided into two groups.32 patients were received surgical
      therapy of single mediastinoscopic esophagectomy with open gastroplasty in group
      A, while 8 patients were received surgical therapy of mediastinoscopic
      esophagectomy combined with laparoscopic lower esophageal and gastric dissection
      in group B. The perioperative complications were recorded. RESULTS: Video
      assisted mediastinoscopic transhiatal esophagectomy was performed successfully
      both in group A and B. It suggested that mediastinoscopy combined with
      laparoscopy be better than single mediastinoscopy because of less blood loss,
      less pain, shorter ICU stay and complete lower mediastinal lymph nodes resection.
      CONCLUSIONS: Video-assisted mediastinoscopic transhiatal esophagectomy combined
      with laparoscopy is a safe and minimally invasive technique with whole esophagus
      and mediastinal lymph node dissection in the clear visualization of the
      mediastinum, reducing the abdominal trauma.

PMID- 21194431
TI  - Prognostic prediction across a gradient of total tumor volume in patients with
      hepatocellular carcinoma undergoing locoregional therapy.
AB  - BACKGROUND: The size and number of tumors are important prognostic indicators for
      hepatocellular carcinoma (HCC). However, it is difficult to assess the prognosis
      for patients with a variable number and size of tumors. By combining these two
      factors, we investigated the role and prognostic accuracy of total tumor volume
      (TTV) for HCC. METHODS: A total of 786 patients undergoing locoregional therapy
      (transarterial chemoembolization, percutaneous radiofrequency ablation and acetic
      acid or ethanol injection) for HCC were prospectively evaluated. RESULTS: The
      mean and median TTV was 177 cm3 (range, 0.1-3,591 cm3) and 21 cm3, respectively.
      Of all, 38%, 29%, 15%, 7% and 11% of patients had TTV of <10 cm3, 10-50 cm3, 50
      200 cm3, 200-500 cm3 and >500 cm3, respectively. TTV was significantly larger in
      patients with higher serum alpha-fetoprotein (AFP) levels or with vascular
      invasion. The Child-Turcotte-Pugh score, performance status, vascular invasion,
      AFP level and TTV were significant independent prognostic predictors in the Cox
      proportional hazards model. After adjustment, patients with TTV 50-200 cm3
      (relative risk [RR]: 1.74, p = 0.009), 200-500 cm3 (RR: 2.15, p = 0.006) and >500
      cm3 (RR: 3.92, p < 0.001) had a significantly increased mortality risk in
      comparison to patients with TTV <10 cm3. CONCLUSIONS: TTV is a feasible
      prognostic predictor across a wide gradient and can be used to predict the
      mortality risk of HCC. Selecting appropriate cutoffs of TTV may help refine the
      design of cancer staging system and treatment planning. Future clinical trials of
      HCC may include this parameter for mortality risk stratification.

PMID- 21194432
TI  - Adaptive immunity to rhinoviruses: sex and age matter.
AB  - BACKGROUND: Rhinoviruses (RV) are key triggers in acute asthma exacerbations.
      Previous studies suggest that men suffer from infectious diseases more frequently
      and with greater severity than women. Additionally, the immune response to most
      infections and vaccinations decreases with age. Most immune function studies do
      not account for such differences, therefore the aim of this study was to
      determine if the immune response to rhinovirus varies with sex or age. METHODS:
      Blood mononuclear cells were isolated from 63 healthy individuals and grouped by
      sex and age (<=50 years old and >=52 years old). Cells were cultured with
      rhinovirus 16 at a multiplicity of infection of 1. The chemokine IP-10 was
      measured at 24 h as an index of innate immunity while IFNgamma and IL-13 were
      measured at 5 days as an index of adaptive immunity. RESULTS: Rhinovirus induced
      IFNgamma and IL-13 was significantly higher in <=50 year old women than in age
      matched men (p < 0.02 and p < 0.05) and >=52 year old women (p < 0.02 and p >
      0.005). There was no sex or age based difference in rhinovirus induced IP-10
      expression. Both IFNgamma and IL-13 were negatively correlated with age in women
      but not in men. CONCLUSIONS: This study suggests that pre-menopausal women have a
      stronger adaptive immune response to rhinovirus infection than men and older
      people, though the mechanisms responsible for these differences remain to be
      determined. Our findings highlight the importance of gender and age balance in
      clinical studies and in the development of new treatments and vaccines.

PMID- 21194433
TI  - Insecticide resistance and malaria transmission: infection rate and oocyst burden
      in Culex pipiens mosquitoes infected with Plasmodium relictum.
AB  - BACKGROUND: The control of most vectors of malaria is threatened by the spread of
      insecticide resistance. One factor that has been hitherto largely overlooked is
      the potential effects of insecticide resistance on the ability of mosquitoes to
      transmit malaria: are insecticide-resistant mosquitoes as good vectors of
      Plasmodium as susceptible ones? The drastic physiological changes that accompany
      the evolution of insecticide resistance may indeed alter the ability of vectors
      to transmit diseases, a possibility that, if confirmed, could have major
      epidemiological consequences. METHODS: Using a novel experimental system
      consisting of the avian malaria parasite (Plasmodium relictum) and its natural
      vector (the mosquito Culex pipiens), two of the most common mechanisms of
      insecticide resistance (esterase overproduction and acetylcholinesterase
      modification) were investigated for their effect on mosquito infection rate and
      parasite burden. For this purpose two types of experiments were carried out using
      (i) insecticide-resistant and susceptible laboratory isogenic lines of Cx.
      pipiens and (ii) wild Cx. pipiens collected from a population where insecticide
      resistant and susceptible mosquitoes coexist in sympatry. RESULTS: The isogenic
      line and wild-caught mosquito experiments were highly consistent in showing no
      effect of either esterase overproduction or of acetylcholinesterase modification
      on either the infection rate or on the oocyst burden of mosquitoes. The only
      determinant of these traits was blood meal size, which was similar across the
      different insecticide resistant categories in both experiments. CONCLUSIONS:
      Insecticide resistance was found to have no effect on Plasmodium development
      within the mosquito. This is the first time this question has been addressed
      using a natural mosquito-Plasmodium combination, while taking care to standardize
      the genetic background against which the insecticide resistance genes operate.
      Infection rate and oocyst burden are but two of the factors that determine the
      vectorial capacity of mosquitoes. Other key determinants of parasite
      transmission, such as mosquito longevity and behaviour, or the parasite's
      incubation time, need to be investigated before concluding on whether insecticide
      resistance influences the ability of mosquitoes to transmit malaria.

PMID- 21194434
TI  - Integrated functional networks of process, tissue, and developmental stage
      specific interactions in Arabidopsis thaliana.
AB  - BACKGROUND: Recent years have seen an explosion in plant genomics, as the
      difficulties inherent in sequencing and functionally analyzing these biologically
      and economically significant organisms have been overcome. Arabidopsis thaliana,
      a versatile model organism, represents an opportunity to evaluate the predictive
      power of biological network inference for plant functional genomics. RESULTS:
      Here, we provide a compendium of functional relationship networks for Arabidopsis
      thaliana leveraging data integration based on over 60 microarray, physical and
      genetic interaction, and literature curation datasets. These include tissue,
      biological process, and development stage specific networks, each predicting
      relationships specific to an individual biological context. These biological
      networks enable the rapid investigation of uncharacterized genes in specific
      tissues and developmental stages of interest and summarize a very large
      collection of A. thaliana data for biological examination. We found validation in
      the literature for many of our predicted networks, including those involved in
      disease resistance, root hair patterning, and auxin homeostasis. CONCLUSIONS:
      These context-specific networks demonstrate that highly specific biological
      hypotheses can be generated for a diversity of individual processes,
      developmental stages, and plant tissues in A. thaliana. All predicted functional
      networks are available online at http://function.princeton.edu/arathGraphle.

PMID- 21194435
TI  - Residents' intentions and actions after patient safety education.
AB  - BACKGROUND: Medical residents are key figures in delivering care and an important
      target group for patient safety education. The objective of this study was to
      assess residents' intentions and actions concerning patient safety improvement
      after patient safety education. METHODS: Four multi-specialty 2-day patient
      safety courses were organized, in which residents from five Dutch hospitals
      participated. At the end of these courses participants were asked to formulate an
      action point to improve patient safety. Three months later semi-structured
      interviews were conducted to reveal actions that were taken, factors that had
      influenced their behaviour and reactions concerning the education. An inductive
      theory approach was used to analyze transcriptions. RESULTS: Out of 71
      participants, sixty-nine (97%) residents were interviewed. In total they had
      formulated 91 action points, which mainly focused on: 'Improving organization of
      own work/Follow policies' and 'Improving culture/Educating colleagues about
      patient safety'. Sixty-two (90%) residents declared to have taken action, and 50
      (55%) action points were fully carried out. Most actions taken were at the level
      of the individual professional, rather than at the level of their social or
      organizational context. Results of actions included adjusting the structure of
      their own work, organizing patient safety education for colleagues, communicating
      more efficiently and in a more structured way with colleagues, and reporting
      incidents. Promoters for action included: 'Awareness of the importance of the
      action to be taken', 'Supportive attitude of colleagues' and 'Having received
      patient safety education'. Barriers included: 'Impeding attitude of colleagues',
      'High work-pressure', 'Hierarchy' and 'Switching of work stations'. CONCLUSIONS:
      After patient safety training, residents reported various intentions to
      contribute to patient safety improvement. Numerous actions were taken, but there
      still is a discrepancy between intentions and actual behaviour. To increase
      residents' participation in patient safety improvement, educational efforts
      should be supplemented with actions to remove experienced barriers, most of which
      are related to the residents' social and organizational context.

PMID- 21194436
TI  - Inflammation in the avian spleen: timing is everything.
AB  - BACKGROUND: The synchrony of an organism with both its external and internal
      environment is critical to well-being and survival. As a result, organisms
      display daily cycles of physiology and behavior termed circadian rhythms. At the
      cellular level, circadian rhythms originate via interlocked autoregulatory
      feedback loops consisting of circadian clock genes and their proteins. These
      regulatory loops provide the molecular framework that enables the intracellular
      circadian timing system necessary to generate and maintain subsequent 24 hr
      rhythms. In the present study we examine the daily control of circadian clock
      genes and regulation of the inflammatory response by the circadian clock in the
      spleen. RESULTS: Our results reveal that circadian clock genes as well as
      proinflammatory cytokines, including Tnfalpha and IL-1beta, display rhythmic
      oscillations of mRNA abundance over a 24 hr cycle. LPS-induced systemic
      inflammation applied at midday vs. midnight reveals a differential response of
      proinflammatory cytokine induction in the spleen, suggesting a daily rhythm of
      inflammation. Exogenous melatonin administration at midday prior to LPS
      stimulation conveys pleiotropic effects, enhancing and repressing inflammatory
      cytokines, indicating melatonin functions as both a pro- and anti-inflammatory
      molecule in the spleen. CONCLUSION: In summary, a daily oscillation of circadian
      clock genes and inflammatory cytokines as well as the ability of melatonin to
      function as a daily mediator of inflammation provides valuable information to aid
      in deciphering how the circadian timing system regulates immune function at the
      molecular level. However, further research is needed to clarify the precise
      mechanisms by which the circadian clock and melatonin have an impact upon daily
      immune functions in the periphery.

PMID- 21194437
TI  - Association of iron overload based quantitative T2* MRI technique and carotid
      intima-media thickness in patients with beta-thalassemia: a cross-sectional
      study.
AB  - BACKGROUND: Body iron status has been implicated in atherosclerotic
      cardiovascular disease. The main hypothesis is that high iron status is
      associated with increased risk of atherosclerosis. We investigated the potential
      role of iron as an additional risk factor promoting atherosclerosis among beta
      thalassemic patients. METHODS: In this cross-sectional study, the liver iron load
      was assessed by quantitative T2* MRI technique and intima-media thickness (IMT)
      of the common carotid artery by high-resolution ultrasound among 119 patients (62
      male, 57 female) with beta-thalassemia (major and intermediate) whose age ranged
      from 10 to 50 years with a mean of 25.6 years. The patients were divided into
      three groups according to the severity of iron loading, obtained by T2*MRI
      technique: group I (normal), group II (mild) and group III (moderate and severe)
      iron load.For elimination of the effect of age on carotid IMT values, the
      patients also were divided into four age groups (10-19 y, 20-29 y, 30-39 y and 40
      50 y). Mean carotid IMT based on the severity of iron loading were compared at
      different age groups, using one way ANOVA analysis for assessing the effect of
      iron loading on carotid IMT. Pearson's coefficient of correlation were used to
      assess the degree of correlation between studied variables (liver T2*, IMT, age).
      RESULTS: There were significant differences in mean carotid IMT based on the
      severity of iron loading at different age groups, with P = 0.003 at 20-29 y, P =
      0.006 at 30-39 y and p = 0.037 at 40-50 y. Age (p = 0.001) and liver T2*(p =
      0.003) had significant correlation with mean carotid IMT independently.At the age
      group of 10-19 years, there were not significant differences in mean carotid IMT
      based on the liver iron loading (p = 0.661).No significant differences also are
      seen in mean carotid IMT between male and female (p = 0.41). CONCLUSIONS: This
      study identified a relationship between body iron status and carotid IMT. This
      relationship support to the hypothesis of a link between body iron load and
      atherosclerosis.

PMID- 21194438
TI  - Circulating endothelial cells are an early predictor in renal cell carcinoma for
      tumor response to sunitinib.
AB  - BACKGROUND: Tyrosine kinase inhibitors (TKI) have enriched the therapeutic
      options in patients with renal cell carcinoma (RCC), which frequently induce
      morphological changes in tumors. However, only little is known about the
      biological activity of TKI. Circulating endothelial cells (CEC) have been
      associated with endothelial damage and, hence, may serve as a putative marker for
      the biological activity of TKI. The main objective of our study was to evaluate
      the predictive value of CEC, monocytes, and soluble vascular endothelial growth
      factor receptor (sVEGFR)-2 in RCC patients receiving sunitinib treatment.
      METHODS: Analyses of CEC, monocytes, and sVEGFR-2 were accomplished for twenty
      six consecutive patients with metastatic RCC who received treatment with
      sunitinib (50 mg, 4 wks on 2 wks off schedule) at our institution in 2005 and
      2006. RESULTS: In RCC patients CEC are elevated to 49 +/- 44/ml (control 8 +/-
      8/ml; P = 0.0001). Treatment with sunitinib is associated with an increase in CEC
      within 28 days of treatment in patients with a Progression free survival (PFS)
      above the median to 111 +/- 61 (P = 0.0109), whereas changes in patients with a
      PFS below the median remain insignificant 69 +/- 61/ml (P = 0.1848). Monocytes
      and sVEGFR2 are frequently altered upon sunitinib treatment, but fail to
      correlate with clinical response, defined by PFS above or below the median.
      CONCLUSIONS: Sunitinib treatment is associated with an early increase of CEC in
      responding patients, suggesting superior endothelial cell damage in these
      patients as a putative predictive biomarker.

PMID- 21194439
TI  - Glycogen synthase kinase-3beta inactivation inhibits tumor necrosis factor-alpha
      production in microglia by modulating nuclear factor kappaB and MLK3/JNK
      signaling cascades.
AB  - BACKGROUND: Deciphering the mechanisms that modulate the inflammatory response
      induced by microglial activation not only improves our insight into
      neuroinflammation but also provides avenues for designing novel therapies that
      could halt inflammation-induced neuronal degeneration. Decreasing glycogen
      synthase kinase-3beta (GSK-3beta) activity has therapeutic benefits in
      inflammatory diseases. However, the exact molecular mechanisms underlying GSK
      3beta inactivation-mediated suppression of the inflammatory response induced by
      microglial activation have not been completely clarified. Tumor necrosis factor
      alpha (TNF-alpha) plays a central role in injury caused by neuroinflammation. We
      investigated the regulatory effect of GSK-3beta on TNF-alpha production by
      microglia to discern the molecular mechanisms of this modulation. METHODS:
      Lipopolysaccharide (LPS) was used to induce an inflammatory response in cultured
      primary microglia or murine BV-2 microglial cells. Release of TNF-alpha was
      measured by ELISA. Signaling molecules were analyzed by western blotting, and
      activation of NF-kappaB and AP-1 was measured by ELISA-based DNA binding analysis
      and luciferase reporter assay. Protein interaction was examined by
      coimmunoprecipitation. RESULTS: Inhibition of GSK-3beta by selective GSK-3beta
      inhibitors or by RNA interference attenuated LPS-induced TNF-alpha production in
      cultured microglia. Exploration of the mechanisms by which GSK-3beta positively
      regulates inflammatory response showed that LPS-induced IkappaB-alpha
      degradation, NF-kappaBp65 nuclear translocation, and p65 DNA binding activity
      were not affected by inhibition of GSK-3beta activity. However, GSK-3beta
      inactivation inhibited transactivation activity of p65 by deacetylating p65 at
      lysine 310. Furthermore, we also demonstrated a functional interaction between
      mixed lineage kinase 3 (MLK3) and GSK-3beta during LPS-induced TNF-alpha
      production in microglia. The phosphorylated levels of MLK3, MKK4, and JNK were
      increased upon LPS treatment. Decreasing GSK-3beta activity blocked MLK3
      signaling cascades through disruption of MLK3 dimerization-induced
      autophosphorylation, ultimately leading to a decrease in TNF-alpha secretion.
      CONCLUSION: These results suggest that inactivation of GSK-3beta might represent
      a potential strategy to downregulate microglia-mediated inflammatory processes.

PMID- 21194440
TI  - Public, private and personal: qualitative research on policymakers' opinions on
      smokefree interventions to protect children in 'private' spaces.
AB  - BACKGROUND: Governments use law to constrain aspects of private activities for
      purposes of protecting health and social wellbeing. Policymakers have a range of
      perceptions and beliefs about what is public or private. An understanding of the
      possible drivers of policymaker decisions about where government can or should
      intervene for health is important, as one way to better guide appropriate policy
      formation. Our aim was to identify obstacles to, and opportunities for,
      government smokefree regulation of private and public spaces to protect children.
      In particular, to seek policymaker opinions on the regulation of smoking in
      homes, cars and public parks and playgrounds in a country with incomplete
      smokefree laws (New Zealand). METHODS: Case study, using structured interviews to
      ask policymakers (62 politicians and senior officials) about their opinions on
      new smokefree legislation for public and private places. Supplementary data was
      obtained from the Factiva media database, on the views of New Zealand local
      authority councillors about policies for smokefree outdoor public places.
      RESULTS: Overall, interviewees thought that government regulation of smoking in
      private places was impractical and unwise. However, there were some differences
      on what was defined as 'private', particularly for cars. Even in public parks,
      smoking was seen by some as a 'personal' decision, and unlikely to be amenable to
      regulation. Most participants believed that educative, supportive and community
      based measures were better and more practical means of reducing smoking in
      private places, compared to regulation. CONCLUSIONS: The constrained view of the
      role of regulation of smoking in public and private domains may be in keeping
      with current political discourse in New Zealand and similar Anglo-American
      countries. Policy and advocacy options to promote additional smokefree measures
      include providing a better voice for childrens' views, increasing information to
      policymakers about the harms to children from secondhand smoke and the example of
      adult smoking, and changing the culture for smoking around children.

PMID- 21194441
TI  - Changes in serum and synovial fluid biomarkers after acute injury (NCT00332254).
AB  - INTRODUCTION: Acute trauma involving the anterior cruciate ligament is believed
      to be a major risk factor for the development of post-traumatic osteoarthritis 10
      to 20 years post-injury. In this study, to better understand the early biological
      changes which occur after acute injury, we investigated synovial fluid and serum
      biomarkers. METHODS: We collected serum from 11 patients without pre-existing
      osteoarthritis from a pilot intervention trial (5 placebo and 6 drug treated)
      using an intra-articular interleukin-1 receptor antagonist (IL-1Ra) therapy, 9 of
      which also supplied matched synovial fluid samples at presentation to the clinic
      after acute knee injury (mean 15.2 +/- 7.2 days) and at the follow-up visit for
      reconstructive surgery (mean 47.6 +/- 12.4 days). To exclude patients with pre
      existing osteoarthritis (OA), the study was limited to individuals younger than
      40 years of age (mean 23 +/- 3.5) with no prior history of joint symptoms or
      trauma. We profiled a total of 21 biomarkers; 20 biomarkers in synovial fluid and
      13 in serum with 12 biomarkers measured in both fluids. Biomarkers analyzed in
      this study were found to be independent of treatment (P > 0.05) as measured by
      Mann-Whitney and two-way ANOVA. RESULTS: We observed significant decreases in
      synovial fluid (sf) biomarker concentrations from baseline to follow-up for (sf)C
      Reactive protein (CRP) (P = 0.039), (sf)lubricin (P = 0.008) and the proteoglycan
      biomarkers: (sf)Glycosaminoglycan (GAG) (P = 0.019), and (sf)Alanine-Arginine
      Glycine-Serine (ARGS) aggrecan (P = 0.004). In contrast, we observed significant
      increases in the collagen biomarkers: (sf)C-terminal crosslinked telopeptide type
      II collagen (CTxII) (P = 0.012), (sf)C1,2C (P = 0.039), (sf)C-terminal
      crosslinked telopeptide type I collagen (CTxI) (P = 0.004), and (sf)N-terminal
      telopeptides of type I collagen (NTx) (P = 0.008). The concentrations of seven
      biomarkers were significantly higher in synovial fluid than serum suggesting
      release from the signal knee: IL-1beta (P < 0.0001), fetal aggrecan FA846 (P =
      0.0001), CTxI (P = 0.0002), NTx (P = 0.012), osteocalcin (P = 0.012), Cartilage
      oligomeric matrix protein (COMP) (P = 0.0001) and matrix metalloproteinase (MMP)
      3 (P = 0.0001). For these seven biomarkers we found significant correlations
      between the serum and synovial fluid concentrations for only CTxI (P = 0.0002),
      NTx (P < 0.0001), osteocalcin (P = 0.0002) and MMP-3 (P = 0.038). CONCLUSIONS:
      These data strongly suggest that the biology after acute injury reflects that
      seen in cartilage explant models stimulated with pro-inflammatory cytokines,
      which are characterized by an initial wave of proteoglycan loss followed by
      subsequent collagen loss. As the rise of collagen biomarkers in synovial fluid
      occurs within the first month after injury, and as collagen loss is thought to be
      irreversible, very early treatment with agents to either reduce inflammation
      and/or reduce collagen loss may have the potential to reduce the onset of future
      post-traumatic osteoarthritis. TRIAL REGISTRATION: The samples used in this study
      were derived from a clinical trial NCT00332254 registered with ClinicalTrial.gov.

PMID- 21194442
TI  - Selection effects may account for better outcomes of the German Disease
      Management Program for type 2 diabetes.
AB  - BACKGROUND: The nationwide German disease management program (DMP) for type 2
      diabetes was introduced in 2003. Meanwhile, results from evaluation studies were
      published, but possible baseline differences between DMP and usual-care patients
      have not been examined. The objective of our study was therefore to find out if
      patient characteristics as socio-demographic variables, cardiovascular risk
      profile or motivation for life style changes influence the chance of being
      enrolled in the German DMP for type 2 diabetes and may therefore account for
      outcome differences between DMP and usual-care patients. METHODS: Case control
      study comparing DMP patients with usual-care patients at baseline and follow up;
      mean follow-up period of 36 +/- 14 months. We used chart review data from 51 GP
      surgeries. Participants were 586 DMP and 250 usual-care patients with type 2
      diabetes randomly selected by chart registry. Data were analysed by multivariate
      logistic and linear regression analyses. Significance levels were p <= 0.05.
      RESULTS: There was a better chance for enrolment if patients a) had a lower risk
      status for diabetes complications, i.e. non-smoking (odds ratio of 1.97, 95%
      confidence interval of 1.11 to 3.48) and lower systolic blood pressure (1.79 for
      120 mmHg vs. 160 mmHg, 1.15 to 2.81); b) had higher activity rates, i.e. were
      practicing blood glucose self-monitoring (1.67, 1.03 to 2.76) and had been
      prescribed a diabetes patient education before enrolment (2.32, 1.29 to 4.19) c)
      were treated with oral medication (2.17, 1.35 to 3.49) and d) had a higher GP
      rated motivation for diabetes education (4.55 for high motivation vs. low
      motivation, 2.21 to 9.36). CONCLUSIONS: At baseline, future DMP patients had a
      lower risk for diabetes complications, were treated more intensively and were
      more active and motivated in managing their disease than usual-care patients.
      This finding a) points to the problem that the German DMP may not reach the
      higher risk patients and b) selection bias may impair the assessment of
      differences in outcome quality between enrolled and usual-care patients.
      Suggestions for dealing with this bias in evaluation studies are being made.

PMID- 21194443
TI  - Genomic mapping of social behavior traits in a F2 cross derived from mice
      selectively bred for high aggression.
AB  - BACKGROUND: Rapid response to selection was previously observed in mice selected
      for high levels of inter-male aggression based on number of attacks displayed in
      a novel social interaction test after isolation housing. Attack levels in this
      high aggression line (NC900) increased significantly within just four generations
      of selective breeding, suggesting the presence of a locus with large effect. We
      conducted an experiment using a small (n ~ 100) F2 cross between the ICR-derived,
      non-inbred NC900 strain and the low aggression inbred strain C57BL/6J, genotyped
      for 154 fully informative SNPs, to determine if a locus with large effect
      controls the high-aggression selection trait. A second goal was to use high
      density SNP genotyping (n = 549,000) in the parental strains to characterize
      residual patterns of heterozygosity within NC900, and evaluate regions that are
      identical by descent (IBD) between NC900 and C57BL/6J, to determine what impacts
      these may have on accuracy and resolution of quantitative trait locus (QTL)
      mapping in the F2 cross. RESULTS: No evidence for a locus with major effect on
      aggressive behavior in mice was identified. However, several QTL with genomewide
      significance were mapped for aggression on chromosomes 7 and 19 and other social
      behavior traits on chromosomes 4, 7, 14, and 19. High density genotyping revealed
      that 28% of the genome is still segregating among the six NC900 females used to
      originate the F2 cross, and that segregating regions are present on every
      chromosome but are of widely different sizes. Regions of IBD between NC900 and
      C57BL/6J are found on every chromosome but are most prominent on chromosomes 10,
      16 and X. No significant differences were found for amounts of heterozygosity or
      prevalence of IBD in QTL regions relative to global analysis. CONCLUSIONS: While
      no major gene was identified to explain the rapid selection response in the NC900
      line, transgressive variation (i.e. where the allele from the C57BL/6J increased
      attack levels) and a significant role for dominant gene action were hallmarks of
      the genetic architecture for aggressive behavior uncovered in this study. The
      high levels of heterozygosity and the distribution of minor allele frequency
      observed in the NC900 population suggest that maintenance of heterozygosity may
      have been under selection in this line.

PMID- 21194444
TI  - Toxic risk of stereotactic body radiotherapy and concurrent helical tomotherapy
      followed by erlotinib for non-small-cell lung cancer treatment--case report.
AB  - BACKGROUND: Stereotactic body radiation therapy (SBRT) applied by helical
      tomotherapy (HT) is feasible for lung cancer in clinical. Using SBRT concurrently
      with erlotinib for non-small cell lung cancer (NSCLC) is not reported previously.
      CASE PRESENTATION: A 77-year-old man with stage III NSCLC, received erlotinib 150
      mg/day, combined with image-guided SBRT via HT. A total tumor dose of 54 Gy/9
      fractions was delivered to the tumor bed. The tumor responded dramatically and
      the combined regimen was well tolerated. After concurrent erlotinib-SBRT,
      erlotinib was continued as maintenance therapy. The patient developed dyspnea
      three months after the combined therapy and radiation pneumonitis with
      interstitial lung disease was suspected. CONCLUSIONS: Combination SBRT, HT, and
      erlotinib therapy provided effective anti-tumor results. Nonetheless, the
      potential risks of enhanced adverse effects between radiation and erlotinib
      should be monitored closely, especially when SBRT is part of the regimen.

PMID- 21194445
TI  - The protein kinase Mzeta network as a bistable switch to store neuronal memory.
AB  - BACKGROUND: Protein kinase Mzeta (PKMzeta), the brain-specific, atypical protein
      kinase C isoform, plays a key role in long-term maintenance of memory. This
      molecule is essential for long-term potentiation of the neuron and various
      modalities of learning such as spatial memory and fear conditioning. It is
      unknown, however, how PKMzeta stores information for long periods of time despite
      molecular turnover. RESULTS: We hypothesized that PKMzeta forms a bistable switch
      because it appears to constitute a positive feedback loop (PKMzeta induces its
      local synthesis) part of which is ultrasensitive (PKMzeta stimulates its
      synthesis through dual pathways). To examine this hypothesis, we modeled the
      biochemical network of PKMzeta with realistic kinetic parameters. Bifurcation
      analyses of the model showed that the system maintains either the up state or the
      down state according to previous inputs. Furthermore, the model was able to
      reproduce a variety of previous experimental results regarding synaptic
      plasticity and learning, which suggested that it captures the essential mechanism
      for neuronal memory. We proposed in vitro and in vivo experiments that would
      critically examine the validity of the model and illuminate the pivotal role of
      PKMzeta in synaptic plasticity and learning. CONCLUSIONS: This study revealed
      bistability of the PKMzeta network and supported its pivotal role in long-term
      storage of memory.

PMID- 21194446
TI  - A two-step site and mRNA-level model for predicting microRNA targets.
AB  - BACKGROUND: Despite experiments showing that the number of microRNA (miRNA)
      target sites is critical for miRNA targeting, most existing methods focus on
      identifying individual miRNA target sites and do not model contributions of
      multiple target sites to miRNA regulation. To address this possible fault, we
      developed a miRNA target prediction model that recognizes the individual
      characteristics of functional binding sites and the global characteristics of
      miRNA-targeted mRNAs. RESULTS: Benchmark experiments showed that this two-step
      model generally had a higher overall performance than other established miRNA
      target prediction algorithms and that the model was especially suited to identify
      true miRNA targets among genes that all contain conserved target sites.
      CONCLUSIONS: This improved performance could partly be explained by the model not
      relying on conservation when predicting targets. The critical factors for the
      model's performance, however, were mRNA-level features that characterized the
      number and strength of individual target sites within the mRNA. The model is
      available for online predictions or as pre-computed predictions on the human
      genome http://tare.medisin.ntnu.no/mirna_target.

PMID- 21194447
TI  - Corticospinal interaction during isometric compensation for modulated forces with
      different frequencies.
AB  - BACKGROUND: During isometric compensation of modulated low-level forces
      corticomuscular coherence (CMC) has been shown to occur in high-beta or gamma
      range. The influence of the frequency of force modulation on CMC has up to now
      remained unexplored. We addressed this question by investigating CMC, motor
      performance, and cortical spectral power during a visuomotor task in which
      subjects had to compensate a modulated force of 8% of the maximum voluntary
      contraction exerted on their right index finger. The effect of three frequencies
      of force modulation (0.6, 1.0 and 1.6 Hz) was tested. EEG, EMG from first dorsal
      interosseus, hand flexor and extensor muscles, and finger position were recorded
      in eight right-handed women. RESULTS: Five subjects showed CMC in gamma- (28-45
      Hz) and three in beta-range (15-30 Hz). Beta- and gamma-range CMC and cortical
      motor spectral power were not modulated by the various frequencies. However, a
      sharp bilateral CMC peak at 1.6 Hz was observed, but only in the five gamma-range
      CMC subjects. The performance error increased linearly with the frequency.
      CONCLUSIONS: Our findings suggest that the frequency of force modulation has no
      effect on the beta- and gamma-range CMC during isometric compensation for
      modulated forces at 8% MVC. The beta- and gamma-range CMC may be related to
      interindividual differences and possibly to strategy differences.

PMID- 21194448
TI  - Contact with HIV prevention services highest in gay and bisexual men at greatest
      risk: cross-sectional survey in Scotland.
AB  - BACKGROUND: Men who have sex with men (MSM) remain the group most at risk of
      acquiring HIV in the UK and new HIV prevention strategies are needed. In this
      paper, we examine what contact MSM currently have with HIV prevention activities
      and assess the extent to which these could be utilised further. METHODS:
      Anonymous, self-complete questionnaires and OrasureTM oral fluid collection kits
      were distributed to men visiting the commercial gay scenes in Glasgow and
      Edinburgh in April/May 2008. 1508 men completed questionnaires (70.5% response
      rate) and 1277 provided oral fluid samples (59.7% response rate); 1318 men were
      eligible for inclusion in the analyses. RESULTS: 82.5% reported some contact with
      HIV prevention activities in the past 12 months, 73.1% obtained free condoms from
      a gay venue or the Internet, 51.1% reported accessing sexual health information
      (from either leaflets in gay venues or via the Internet), 13.5% reported talking
      to an outreach worker and 8.0% reported participating in counselling on sexual
      health or HIV prevention. Contact with HIV prevention activities was associated
      with frequency of gay scene use and either HIV or other STI testing in the past
      12 months, but not with sexual risk behaviours. Utilising counselling was also
      more likely among men who reported having had an STI in the past 12 months and
      HIV-positive men. CONCLUSIONS: Men at highest risk, and those likely to be in
      contact with sexual health services, are those who report most contact with a
      range of current HIV prevention activities. Offering combination prevention,
      including outreach by peer health workers, increased uptake of sexual health
      services delivering behavioural and biomedical interventions, and supported by
      social marketing to ensure continued community engagement and support, could be
      the way forward. Focused investment in the needs of those at highest risk,
      including those diagnosed HIV-positive, may generate a prevention dividend in the
      long term.

PMID- 21194449
TI  - 454 sequencing reveals extreme complexity of the class II Major
      Histocompatibility Complex in the collared flycatcher.
AB  - BACKGROUND: Because of their functional significance, the Major
      Histocompatibility Complex (MHC) class I and II genes have been the subject of
      continuous interest in the fields of ecology, evolution and conservation. In some
      vertebrate groups MHC consists of multiple loci with similar alleles; therefore,
      the multiple loci must be genotyped simultaneously. In such complex systems,
      understanding of the evolutionary patterns and their causes has been limited due
      to challenges posed by genotyping. RESULTS: Here we used 454 amplicon sequencing
      to characterize MHC class IIB exon 2 variation in the collared flycatcher, an
      important organism in evolutionary and immuno-ecological studies. On the basis of
      over 152,000 sequencing reads we identified 194 putative alleles in 237
      individuals. We found an extreme complexity of the MHC class IIB in the collared
      flycatchers, with our estimates pointing to the presence of at least nine
      expressed loci and a large, though difficult to estimate precisely, number of
      pseudogene loci. Many similar alleles occurred in the pseudogenes indicating
      either a series of recent duplications or extensive concerted evolution. The
      expressed alleles showed unambiguous signals of historical selection and the
      occurrence of apparent interlocus exchange of alleles. Placing the collared
      flycatcher's MHC sequences in the context of passerine diversity revealed
      transspecific MHC class II evolution within the Muscicapidae family. CONCLUSIONS:
      454 amplicon sequencing is an effective tool for advancing our understanding of
      the MHC class II structure and evolutionary patterns in Passeriformes. We found a
      highly dynamic pattern of evolution of MHC class IIB genes with strong signals of
      selection and pronounced sequence divergence in expressed genes, in contrast to
      the apparent sequence homogenization in pseudogenes. We show that next generation
      sequencing offers a universal, affordable method for the characterization and, in
      perspective, genotyping of MHC systems of virtually any complexity.

PMID- 21194450
TI  - Responses of Massachusetts hospitals to a state mandate to collect race,
      ethnicity and language data from patients: a qualitative study.
AB  - BACKGROUND: A Massachusetts regulation implemented in 2007 has required all acute
      care hospitals to report patients' race, ethnicity and preferred language using
      standardized methodology based on self-reported information from patients. This
      study assessed implementation of the regulation and its impact on the use of race
      and ethnicity data in performance monitoring and quality improvement within
      hospitals. METHODS: Thematic analysis of semi-structured interviews with
      executives from a representative sample of 28 Massachusetts hospitals in 2009.
      RESULTS: The number of hospitals using race, ethnicity and language data
      internally beyond refining interpreter services increased substantially from 11
      to 21 after the regulation. Thirteen of these hospitals were utilizing patient
      race and ethnicity data to identify disparities in quality performance measures
      for a variety of clinical processes and outcomes, while 16 had developed patient
      services and community outreach programs based on findings from these data.
      Commonly reported barriers to data utilization include small numbers within
      categories, insufficient resources, information system requirements, and lack of
      direction from the state. CONCLUSIONS: The responses of Massachusetts hospitals
      to this new state regulation indicate that requiring the collection of race,
      ethnicity and language data can be an effective method to promote performance
      monitoring and quality improvement, thereby setting the stage for federal
      standards and incentive programs to eliminate racial and ethnic disparities in
      the quality of health care.

PMID- 21194451
TI  - Reliability of an injury scoring system for horses.
AB  - BACKGROUND: The risk of injuries is of major concern when keeping horses in
      groups and there is a need for a system to record external injuries in a
      standardised and simple way. The objective of this study, therefore, was to
      develop and validate a system for injury recording in horses and to test its
      reliability and feasibility under field conditions. METHODS: Injuries were
      classified into five categories according to severity. The scoring system was
      tested for intra- and inter-observer agreement as well as agreement with a
      'golden standard' (diagnosis established by a veterinarian). The scoring was done
      by 43 agricultural students who classified 40 photographs presented to them twice
      in a random order, 10 days apart. Attribute agreement analysis was performed
      using Kendall's coefficient of concordance (Kendall's W), Kendall's correlation
      coefficient (Kendall's tau) and Fleiss' kappa. The system was also tested on a
      sample of 100 horses kept in groups where injury location was recorded as well.
      RESULTS: Intra-observer agreement showed Kendall's W ranging from 0.94 to 0.99
      and 86% of observers had kappa values above 0.66 (substantial agreement). Inter
      observer agreement had an overall Kendall's W of 0.91 and the mean kappa value
      was 0.59 (moderate). Agreement for all observers versus the 'golden standard' had
      Kendall's tau of 0.88 and the mean kappa value was 0.66 (substantial). The system
      was easy to use for trained persons under field conditions. Injuries of the more
      serious categories were not found in the field trial. CONCLUSION: The proposed
      injury scoring system is easy to learn and use also for people without a
      veterinary education, it shows high reliability, and it is clinically useful. The
      injury scoring system could be a valuable tool in future clinical and
      epidemiological studies.

PMID- 21194452
TI  - A powerful transgenic tool for fate mapping and functional analysis of newly
      generated neurons.
AB  - BACKGROUND: Lack of appropriate tools and techniques to study fate and functional
      integration of newly generated neurons has so far hindered understanding of
      neurogenesis' relevance under physiological and pathological conditions. Current
      analyses are either dependent on mitotic labeling, for example BrdU-incorporation
      or retroviral infection, or on the detection of transient immature neuronal
      markers. Here, we report a transgenic mouse model (DCX-CreERT2) for time-resolved
      fate analysis of newly generated neurons. This model is based on the expression
      of a tamoxifen-inducible Cre recombinase under the control of a doublecortin
      (DCX) promoter, which is specific for immature neuronal cells in the CNS.
      RESULTS: In the DCX-CreERT2 transgenic mice, expression of CreERT2 was restricted
      to DCX+ cells. In the CNS of transgenic embryos and adult DCX-CreERT2 mice,
      tamoxifen administration caused the transient translocation of CreERT2 to the
      nucleus, allowing for the recombination of loxP-flanked sequences. In our system,
      tamoxifen administration at E14.5 resulted in reporter gene activation throughout
      the developing CNS of transgenic embryos. In the adult CNS, neurogenic regions
      were the primary sites of tamoxifen-induced reporter gene activation. In
      addition, reporter expression could also be detected outside of neurogenic
      regions in cells physiologically expressing DCX (e.g. piriform cortex, corpus
      callosum, hypothalamus). Four weeks after recombination, the vast majority of
      reporter-expressing cells were found to co-express NeuN, revealing the neuronal
      fate of DCX+ cells upon maturation. CONCLUSIONS: This first validation
      demonstrates that our new DCX-CreERT2 transgenic mouse model constitutes a
      powerful tool to investigate neurogenesis, migration and their long-term fate of
      neuronal precursors. Moreover, it allows for a targeted activation or deletion of
      specific genes in neuronal precursors and will thereby contribute to unravel the
      molecular mechanisms controlling neurogenesis.

PMID- 21194453
TI  - Association between perinatal depression in mothers and the risk of childhood
      infections in offspring: a population-based cohort study.
AB  - BACKGROUND: Previous studies have suggested that children of mothers who
      experience depression during the perinatal period may have more infections, but
      such studies are few in number and none have been carried out in the United
      Kingdom (UK) population. The aim of this study was to investigate the association
      between perinatal depression in mothers and the risk of childhood infections in
      offspring in the UK general population. METHODS: We used data from The Health
      Improvement Network (THIN), a large database of electronic primary care medical
      records to conduct a cohort study among all first-born singleton children born
      and enrolled in THIN between 1988 and 2004. We used Poisson regression to compare
      the incidence of gastrointestinal infections and lower respiratory tract
      infections reported between birth and age 4 years among children of mothers with
      a record of perinatal depression with those born to mothers with no such history.
      RESULTS: Children of mothers with perinatal depression had a 40% increased risk
      of gastrointestinal infections and a 27% increased risk of lower respiratory
      tract infections compared with children of mothers without perinatal depression
      (incidence rate ratios = 1.40 and 1.27; 95% confidence intervals 1.37-1.42 and
      1.22-1.32, respectively). On restricting to antibiotic-treated infections there
      was a slight increase in the magnitude of association with gastrointestinal
      infections but a decrease in that with lower respiratory tract infections
      (incidence rate ratios = 1.47 and 1.19; 95% confidence intervals 1.34-1.61 and
      1.11-1.27, respectively). CONCLUSIONS: Maternal perinatal depression is
      associated with increased rates of childhood gastrointestinal infections,
      particularly more severe infections, and lower respiratory tract infections in
      the UK. Preventing maternal perinatal depression may avoid substantial morbidity
      among offspring, although further work is also needed to investigate the detailed
      reasons for these findings.

PMID- 21194454
TI  - Differences in the ability to suppress interferon beta production between allele
      A and allele B NS1 proteins from H10 influenza A viruses.
AB  - BACKGROUND: In our previous study concerning the genetic relationship among H10
      avian influenza viruses with different pathogenicity in mink (Mustela vison), we
      found that these differences were related to amino acid variations in the NS1
      protein. In this study, we extend our previous work to further investigate the
      effect of the NS1 from different gene pools on type I IFN promoter activity, the
      production of IFN-beta, as well as the expression of the IFN-beta mRNA in
      response to poly I:C. RESULTS: Using a model system, we first demonstrated that
      NS1 from A/mink/Sweden/84 (H10N4) (allele A) could suppress an interferon
      stimulated response element (ISRE) reporter system to about 85%. The other NS1
      (allele B), from A/chicken/Germany/N/49 (H10N7), was also able to suppress the
      reporter system, but only to about 20%. The differences in the abilities of the
      two NS1s from different alleles to suppress the ISRE reporter system were clearly
      reflected by the protein and mRNA expressions of IFN-beta as shown by ELISA and
      RT-PCR assays. CONCLUSIONS: These studies reveal that different non-structural
      protein 1 (NS1) of influenza viruses, one from allele A and another from allele
      B, show different abilities to suppress the type I interferon beta expression. It
      has been hypothesised that some of the differences in the different abilities of
      the alleles to suppress ISRE were because of the interactions and inhibitions at
      later stages from the IFN receptor, such as the JAK/STAT pathway. This might
      reflect the additional effects of the immune evasion potential of different NS1s.

PMID- 21194455
TI  - A system dynamics analysis determining willingness to wait and pay for the
      implementation of data standards in clinical research.
AB  - BACKGROUND: Industry standards provide rigorous descriptions of required data
      presentation, with the aim of ensuring compatibility across different clinical
      studies. However despite their crucial importance, these standards are often not
      used as expected in the development of clinical research. The reasons for this
      lack of compliance could be related to the high cost and time-intensive nature of
      the process of data standards implementation. The objective of this study was to
      evaluate the value of the extra time and cost required for different levels of
      data standardisation and the likelihood of researchers to comply with these
      levels. Since we believe that the cost and time necessary for the implementation
      of data standards can change over time, System Dynamics (SD) analysis was used to
      investigate how these variables interact and influence the adoption of data
      standards by clinical researchers. METHODS: Three levels of data standards
      implementation were defined through focus group discussion involving four
      clinical research investigators. Ten Brazilian and eighteen American
      investigators responded to an online questionnaire which presented possible
      standards implementation scenarios, with respondents asked to choose one of two
      options available in each scenario. A random effects ordered probit model was
      used to estimate the effect of cost and time on investigators' willingness to
      adhere to data standards. The SD model was used to demonstrate the relationship
      between degrees of data standardisation and subsequent variation in cost and time
      required to start the associated study. RESULTS: A preference for low cost and
      rapid implementation times was observed, with investigators more likely to incur
      costs than to accept a time delay in project start-up. SD analysis indicated that
      although initially extra time and cost are necessary for clinical study
      standardisation, there is a decrease in both over time. CONCLUSIONS: Future
      studies should explore ways of creating mechanisms which decrease the time and
      cost associated with standardisation processes. In addition, the fact that the
      costs and time necessary for data standards implementation decrease with time
      should be made known to the wider research community. Policy makers should
      attempt to match their data standardisation policies better with the expectations
      of researchers.

PMID- 21194456
TI  - Mutations in the E2-PePHD region of hepatitis C virus genotype-3a and correlation
      with response to interferon and ribavirin combination therapy in Pakistani
      patients.
AB  - Hepatitis C is a major health problem affecting more than 200 million individuals
      in the world. Current treatment regimen consisting of interferon alpha and
      ribavirin does not always succeed in eliminating the virus completely from
      patient's body. One of the mechanisms by which virus evades the antiviral effect
      of interferon alpha involves protein kinase (PKR) eukaryotic initiation factor 2
      alpha (eIF2a) phosphorylation homology domain (PePHD). This domain in genotype 1
      strains is reportedly homologous to PKR and its target eIF2a. By binding to PKR,
      PePHD inhibits its activity and therefore cause virus to evade antiviral activity
      of interferon (IFN). Many studies have correlated substitutions in this domain to
      the treatment response and lead to inconclusive results. Some studies suggested
      that substitutions favor response while others emphasized that no correlation
      exists. In the present study we therefore compared sequences of PePHD domain of
      thirty one variants of six hepatitis C virus patients of genotype 3. Three of our
      HCV 3a infected patients showed rapid virological response to interferon alpha
      and ribavirin combination therapy whereas the remaining three had breakthrough to
      the same combination therapy. It is found that PePHD domain is not entirely
      conserved and has substitutions in some isolates irrespective of the treatment
      response. However substitution of glutamine (Q) with Leucine (L) in one of the
      breakthrough responders made it more identical to HCV genotype 1a. These
      substitutions in the breakthrough responders also tended to increase average
      hydrophilic activity thus making binding of PePHD to PKR and inhibition of PKR
      more favorable.

PMID- 21194457
TI  - Mitochondrial pathogenic mutations are population-specific.
AB  - BACKGROUND: Surveying deleterious variation in human populations is crucial for
      our understanding, diagnosis and potential treatment of human genetic
      pathologies. A number of recent genome-wide analyses focused on the prevalence of
      segregating deleterious alleles in the nuclear genome. However, such studies have
      not been conducted for the mitochondrial genome. RESULTS: We present a systematic
      survey of polymorphisms in the human mitochondrial genome, including those
      predicted to be deleterious and those that correspond to known pathogenic
      mutations. Analyzing 4458 completely sequenced mitochondrial genomes we
      characterize the genetic diversity of different types of single nucleotide
      polymorphisms (SNPs) in African (L haplotypes) and non-African (M and N
      haplotypes) populations. We find that the overall level of polymorphism is higher
      in the mitochondrial compared to the nuclear genome, although the mitochondrial
      genome appears to be under stronger selection as indicated by proportionally
      fewer nonsynonymous than synonymous substitutions. The African mitochondrial
      genomes show higher heterozygosity, a greater number of polymorphic sites and
      higher frequencies of polymorphisms for synonymous, benign and damaging
      polymorphism than non-African genomes. However, African genomes carry
      significantly fewer SNPs that have been previously characterized as pathogenic
      compared to non-African genomes. CONCLUSIONS: Finding SNPs classified as
      pathogenic to be the only category of polymorphisms that are more abundant in non
      African genomes is best explained by a systematic ascertainment bias that favours
      the discovery of pathogenic polymorphisms segregating in non-African populations.
      This further suggests that, contrary to the common disease-common variant
      hypothesis, pathogenic mutations are largely population-specific and different
      SNPs may be associated with the same disease in different populations. Therefore,
      to obtain a comprehensive picture of the deleterious variability in the human
      population, as well as to improve the diagnostics of individuals carrying African
      mitochondrial haplotypes, it is necessary to survey different populations
      independently. REVIEWERS: This article was reviewed by Dr Mikhail Gelfand, Dr
      Vasily Ramensky (nominated by Dr Eugene Koonin) and Dr David Rand (nominated by
      Dr Laurence Hurst).

PMID- 21194459
TI  - Morphologic complexity of epithelial architecture for predicting invasive breast
      cancer survival.
AB  - BACKGROUND: Precise criteria for optimal patient selection for adjuvant
      chemotherapy remain controversial and include subjective components such as
      tumour morphometry (pathological grade). There is a need to replace subjective
      criteria with objective measurements to improve risk assessment and therapeutic
      decisions. We assessed the prognostic value of fractal dimension (an objective
      measure of morphologic complexity) for invasive ductal carcinoma of the breast.
      METHODS: We applied fractal analysis to pan-cytokeratin stained tissue microarray
      (TMA) cores derived from 379 patients. Patients were categorized according to low
      (<1.56, N = 141), intermediate (1.56-1.75, N = 148), and high (>1.75, N = 90)
      fractal dimension. Cox proportional-hazards regression was used to assess the
      relationship between disease-specific and overall survival and fractal dimension,
      tumour size, grade, nodal status, estrogen receptor status, and HER-2/neu status.
      RESULTS: Patients with higher fractal score had significantly lower disease
      specific 10-year survival (25.0%, 56.4%, and 69.4% for high, intermediate, and
      low fractal dimension, respectively, p < 0.001). Overall 10-year survival showed
      a similar association. Fractal dimension, nodal status, and grade were the only
      significant (P < 0.05) independent predictors for both disease-specific and
      overall survival. Among all of the prognosticators, the fractal dimension hazard
      ratio for disease-specific survival, 2.6 (95% confidence interval (CI) = 1.4,4.8;
      P = 0.002), was second only to the slightly higher hazard ratio of 3.1 (95% CI =
      1.9,5.1; P < 0.001) for nodal status. As for overall survival, fractal dimension
      had the highest hazard ratio, 2.7 (95% CI = 1.6,4.7); P < 0.001). Split-sample
      cross-validation analysis suggests these results are generalizable. CONCLUSION:
      Except for nodal status, morphologic complexity of breast epithelium as measured
      quantitatively by fractal dimension was more strongly and significantly
      associated with disease-specific and overall survival than standard
      prognosticators.

PMID- 21194458
TI  - Selected pharmacokinetic issues of the use of antiepileptic drugs and parenteral
      nutrition in critically ill patients.
AB  - OBJECTIVES: To conduct a systematic review for the evidence supporting or
      disproving the reality of parenteral nutrition- antiepileptic drugs interaction,
      especially with respect to the plasma protein-binding of the drug. METHODS: The
      articles related to the topic were identified through Medline and PubMed search
      (1968-Feburary 2010) for English language on the interaction between parenteral
      nutrition and antiepileptic drugs; the search terms used were anti-epileptic
      drugs, parenteral nutrition, and/or interaction, and/or in vitro. The search
      looked for prospective randomized and nonrandomized controlled studies;
      prospective nonrandomized uncontrolled studies; retrospective studies; case
      reports; and in vitro studies. Full text of the articles were then traced from
      the Universiti Sains Malaysia (USM) library subscribed databases, including Wiley
      Blackwell Library, Cochrane Library, EBSCOHost, OVID, ScienceDirect, SAGE
      Premier, Scopus, SpringerLINK, and Wiley InterScience. The articles from journals
      not listed by USM library were traced through inter library loan. RESULTS: There
      were interactions between parenteral nutrition and drugs, including
      antiepileptics. Several guidelines were designed for the management of illnesses
      such as traumatic brain injuries or cancer patients, involving the use of
      parenteral nutrition and antiepileptics. Moreover, many studies demonstrated the
      in vitro and in vivo parenteral nutrition -drugs interactions, especially with
      antiepileptics. CONCLUSIONS: There was no evidence supporting the existence of
      parenteral nutrition-antiepileptic drugs interaction. The issue has not been
      studied in formal researches, but several case reports and anecdotes demonstrate
      this drug-nutrition interaction. However, alteration in the drug-free fraction
      result from parenteral nutrition-drug (i.e. antiepileptics) interactions may
      necessitate scrupulous reassessment of drug dosages in patients receiving these
      therapies. This reassessment may be particularly imperative in certain clinical
      situations characterized by hypoalbuminemia (e.g., burn patients).

PMID- 21194460
TI  - HLA-matched sibling transplantation with G-CSF mobilized PBSCs and BM decreases
      GVHD in adult patients with severe aplastic anemia.
AB  - BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an
      effective treatment for severe aplastic anemia (SAA). However, graft failure and
      graft-versus-host disease (GVHD) are major causes of the early morbidity in Allo
      HSCT. METHODS: To reduce graft failure and GVHD, we treated fifteen patients with
      SAA using high- dose of HSCT with both G-CSF mobilized PB and BMSCs from HLA
      identical siblings to treat patients with SAA. RESULTS: All patients had
      successful bone marrow engraftment. Only one patient had late rejection. Median
      time to ANC greater than 0.5 * 10(9)/L and platelet counts greater than 20 *
      10(9)/L was 12 and 16.5 days, respectively. No acute GVHD was observed. The
      incidence of chronic GVHD was 6.67%. The total three-year probability of disease
      free survival was 79.8%. CONCLUSION: HSCT with both G-CSF mobilized PB and BMSCs
      is a promising approach for heavily transfused and/or allo-immunized patients
      with SAA.

PMID- 21194461
TI  - Association between synovial fluid levels of aggrecan ARGS fragments and
      radiographic progression in knee osteoarthritis.
AB  - INTRODUCTION: Aggrecanase cleavage at the (392)Glu-(393)Ala bond in the
      interglobular domain (IGD) of aggrecan, releasing N-terminal (393)ARGS fragments,
      is an early key event in arthritis and joint injuries. We determined whether
      synovial fluid (SF) levels of ARGS-aggrecan distinguish subjects with progressive
      radiographic knee osteoarthritis (ROA) from those with stable or no ROA. METHODS:
      We studied 141 subjects who, at examination A, had been given meniscectomies an
      average of 18 years earlier (range, 15 to 22 years). Seventeen individuals
      without surgery, and without known injury to the menisci or cruciate ligaments,
      were used as references. At examinations A and B, with a mean follow-up time of
      7.5 years, we obtained SF and standing tibiofemoral and skyline patellofemoral
      radiographs. SF ARGS-aggrecan was measured with an electrochemiluminescence
      immunoassay, and we graded radiographs according to the OARSI atlas. The
      association between SF ARGS levels at examination A and progression of
      radiographic features of knee OA between examinations A and B was assessed by
      using logistic regression adjusted for age, gender, body mass index, and time
      between examinations, and stratified by ROA status at examination A. RESULTS: We
      found a weak negative association between SF ARGS concentrations and loss of
      joint space: the likelihood of progression of radiographic joint space narrowing
      decreased 0.9 times per picomole per milliliter increase in ARGS (odds ratio (OR)
      0.89; 95% confidence interval (CI), 0.79 to 0.996). In subjects with and without
      preexisting ROA at examination A, the association was OR, 0.96; 0.81 to 1.13; and
      0.77; 0.62 to 0.95, respectively. Average levels of SF ARGS 18 years after
      meniscectomy were no different from those of reference subjects and were not
      correlated to radiographic status at examination A. CONCLUSIONS: In subjects with
      previous knee meniscectomy but without ROA, levels of SF ARGS-aggrecan were
      weakly and inversely associated with increased loss of joint space over a period
      of 7.5 years.

PMID- 21194462
TI  - Antigenic analysis of classical swine fever virus E2 glycoprotein using pig
      antibodies identifies residues contributing to antigenic variation of the vaccine
      C-strain and group 2 strains circulating in China.
AB  - BACKGROUND: Glycoprotein E2, the immunodominant protein of classical swine fever
      virus (CSFV), can induce neutralizing antibodies and confer protective immunity
      in pigs. Our previous phylogenetic analysis showed that subgroup 2.1 viruses
      branched away from subgroup 1.1, the vaccine C-strain lineage, and became
      dominant in China. The E2 glycoproteins of CSFV C-strain and recent subgroup 2.1
      field isolates are genetically different. However, it has not been clearly
      demonstrated how this diversity affects antigenicity of the protein. RESULTS:
      Antigenic variation of glycoprotein E2 was observed not only between CSFV vaccine
      C-strain and subgroup 2.1 strains, but also among strains of the same subgroup
      2.1 as determined by ELISA-based binding assay using pig antisera to the C-strain
      and a representative subgroup 2.1 strain QZ-07 currently circulating in China.
      Antigenic incompatibility of E2 proteins markedly reduced neutralization
      efficiency against heterologous strains. Single amino acid substitutions of
      D705N, L709P, G713E, N723S, and S779A on C-strain recombinant E2 (rE2) proteins
      significantly increased heterologous binding to anti-QZ-07 serum, suggesting that
      these residues may be responsible for the antigenic variation between the C
      strain and subgroup 2.1 strains. Notably, a G713E substitution caused the most
      dramatic enhancement of binding of the variant C-strain rE2 protein to anti-QZ-07
      serum. Multiple sequence alignment revealed that the glutamic acid residue at
      this position is conserved within group 2 strains, while the glycine residue is
      invariant among the vaccine strains, highlighting the role of the residue at this
      position as a major determinant of antigenic variation of E2. A variant Simpson's
      index analysis showed that both codons and amino acids of the residues
      contributing to antigenic variation have undergone similar diversification.
      CONCLUSIONS: These results demonstrate that CSFV vaccine C-strain and group 2
      strains circulating in China differ in the antigenicity of their E2
      glycoproteins. Systematic site-directed mutagenesis of the antigenic units has
      revealed residues that limit cross-reactivity. Our findings may be useful for the
      development of serological differential assays and improvement of immunogenicity
      of novel classical swine fever vaccines.

PMID- 21194463
TI  - Sparsification of RNA structure prediction including pseudoknots.
AB  - BACKGROUND: Although many RNA molecules contain pseudoknots, computational
      prediction of pseudoknotted RNA structure is still in its infancy due to high
      running time and space consumption implied by the dynamic programming
      formulations of the problem. RESULTS: In this paper, we introduce sparsification
      to significantly speedup the dynamic programming approaches for pseudoknotted RNA
      structure prediction, which also lower the space requirements. Although
      sparsification has been applied to a number of RNA-related structure prediction
      problems in the past few years, we provide the first application of
      sparsification to pseudoknotted RNA structure prediction specifically and to
      handling gapped fragments more generally - which has a much more complex
      recursive structure than other problems to which sparsification has been applied.
      We analyse how to sparsify four pseudoknot structure prediction algorithms, among
      those the most general method available (the Rivas-Eddy algorithm) and the
      fastest one (Reeder-Giegerich algorithm). In all algorithms the number of
      "candidate" substructures to be considered is reduced. CONCLUSIONS: Our
      experimental results on the sparsified Reeder-Giegerich algorithm suggest a
      linear speedup over the unsparsified implementation.

PMID- 21194464
TI  - 6-Nitro-2-(3-hydroxypropyl)-1H-benz[de]isoquinoline-1,3-dione, a potent antitumor
      agent, induces cell cycle arrest and apoptosis.
AB  - BACKGROUND: Anticancer activities of several substituted naphthalimides (1H
      benz[de]isoquinoline-1,3-diones) are well documented. Some of them have undergone
      Phase I-II clinical trials. Presently a series of ten N-(hydroxyalkyl)
      naphthalimides (compounds 1a-j) were evaluated as antitumor agents. METHODS:
      Compounds 1a-j were initially screened in MOLT-4, HL-60 and U-937 human tumor
      cell lines and results were compared with established clinical drugs.
      Cytotoxicities of compounds 1d and 1i were further evaluated in a battery of
      human tumor cell lines and in normal human peripheral blood mononuclear cells.
      Cell cycle analysis of compound 1i treated MOLT-4 cells was studied by flow
      cytometry. Its apoptosis inducing effect was carried out in MOLT-4 and HL-60
      cells by flow cytometry using annexin V-FITC/PI double staining method. The
      activities of caspase-3 and caspase-6 in MOLT-4 cells following incubation with
      compound 1i were measured at different time intervals. Morphology of the MOLT-4
      cells after treatment with 1i was examined under light microscope and
      transmission electron microscope. 3H-Thymidine and 3H-uridine incorporation in S
      180 cells in vitro following treatment with 8 MUM concentration of compounds 1d
      and 1i were studied. RESULTS: 6-Nitro-2-(3-hydroxypropyl)-1H-benz[de]isoquinoline
      1,3-dione (compound 1i), has exhibited maximum activity as it induced significant
      cytotoxicity in 8 out of 13 cell lines employed. Interestingly it did not show
      any cytotoxicity against human PBMC (IC50 value 273 MUM). Cell cycle analysis of
      compound 1i treated MOLT-4 cells demonstrated rise in sub-G1 fraction and
      concomitant accumulation of cells in S and G2/M phases, indicating up-regulation
      of apoptosis along with mitotic arrest and/or delay in exit of daughter cells
      from mitotic cycle respectively. Its apoptosis inducing effect was confirmed in
      flow cytometric study in MOLT-4 and the action was mediated by activation of both
      caspase 3 and 6. Light and transmission electron microscopic studies corroborated
      its apoptosis inducing efficacy at a concentration of 10 MUM in MOLT-4 cells. Its
      apoptosis induction was also observed in HL-60 cells to an extent much greater
      than well known apoptosis inducing agents as camptothecin and cis-platin at 10
      MUM concentration each. It significantly inhibited DNA and RNA synthesis in S
      180. CONCLUSIONS: In essence, compound 1i showed potential as an antitumor agent.

PMID- 21194465
TI  - Description of Hymenolepis microstoma (Nottingham strain): a classical tapeworm
      model for research in the genomic era.
AB  - BACKGROUND: Hymenolepis microstoma (Dujardin, 1845) Blanchard, 1891, the mouse
      bile duct tapeworm, is a rodent/beetle-hosted laboratory model that has been used
      in research and teaching since its domestication in the 1950s. Recent
      characterization of its genome has prompted us to describe the specific strain
      that underpins these data, anchoring its identity and bringing the 150+ year-old
      original description up-to-date. RESULTS: Morphometric and ultrastructural
      analyses were carried out on laboratory-reared specimens of the 'Nottingham'
      strain of Hymenolepis microstoma used for genome characterization. A contemporary
      description of the species is provided including detailed illustration of adult
      anatomy and elucidation of its taxonomy and the history of the specific
      laboratory isolate. CONCLUSIONS: Our work acts to anchor the specific strain from
      which the H. microstoma genome has been characterized and provides an anatomical
      reference for researchers needing to employ a model tapeworm system that enables
      easy access to all stages of the life cycle. We review its classification, life
      history and development, and briefly discuss the genome and other model systems
      being employed at the beginning of a genomic era in cestodology.

PMID- 21194466
TI  - Group interventions to improve health outcomes: a framework for their design and
      delivery.
AB  - BACKGROUND: Delivering an intervention to a group of patients to improve health
      outcomes is increasingly popular in public health and primary care, yet "group"
      is an umbrella term which encompasses a complex range of aims, theories,
      implementation processes and evaluation methods. We propose a framework for the
      design and process evaluation of health improvement interventions occurring in a
      group setting, which will assist practitioners, researchers and policy makers.
      METHODS: We reviewed the wider literature on health improvement interventions
      delivered to patient groups and identified a gap in the literature for designing,
      evaluating and reporting these interventions. We drew on our experiences
      conducting systematic reviews, intervention, mixed method and ethnographic
      studies of groups for breastfeeding and weight management. A framework for health
      improvement group design and delivery evolved through an iterative process of
      primary research, reference to the literature and research team discussion.
      RESULTS: Although there is an extensive literature on group processes in
      education, work, politics and psychological therapies, far less is known about
      groups where the aim is health improvement. Theories of behaviour change which
      are validated for individual use are often assumed to be generalisable to group
      settings, without being rigorously tested. Health improvement or behaviour change
      interventions delivered in a group setting are complex adaptive social processes
      with interactions between the group leader, participants, and the wider community
      and environment. Ecological models of health improvement, which embrace the
      complex relationship between behaviour, systems and the environment may be more
      relevant than an individual approach to behaviour change. CONCLUSION: The
      evidence for effectiveness and cost-effectiveness of group compared with one-to
      one interventions for many areas of health improvement in public health and
      primary care is weak or unknown. Our proposed framework is the first step towards
      advocating a more systematic approach to designing, evaluating and reporting
      interventions in group settings, which is necessary to improve this currently
      weak evidence base. This framework will enable policy makers and practitioners to
      be better informed about what works, how it works and in which contexts when
      aiming to improve health in a group setting.

PMID- 21194467
TI  - Adiponectin is a potential catabolic mediator in osteoarthritis cartilage.
AB  - INTRODUCTION: Adiponectin has been implicated in the pathogenesis of
      osteoarthritis (OA). We studied the effects of adiponectin on the OA cartilage
      homeostasis. METHODS: Immunohistochemical analysis was performed to evaluate
      differential expression of adiponectin receptors (AdipoRs) in nonlesional and
      lesional areas of OA cartilage. Cartilage and chondrocytes from the knee joints
      of primary OA patients were cultured in the presence of adiponectin (0~30
      MUg/ml). The levels of total nitric oxide (NO), matrix metalloproteinase (MMP)-1,
      -3, and -13, and tissue inhibitor of metalloproteinase (TIMP)-1 were measured in
      the conditioned media. The levels of inducible NO synthase (iNOS) and MMPs were
      determined with the quantitative real-time reverse transcription-polymerase chain
      reaction. The concentrations of collagenase-cleaved type II collagen neoepitope
      (C1-2C) were determined in the supernatant of adiponectin-stimulated OA cartilage
      explants. The effects of kinase and NOS inhibitors were evaluated in the
      adiponectin-stimulated chondrocytes. RESULTS: The expression levels of both
      AdipoR1 and AdipoR2 were significantly higher in lesional than in nonlesional
      areas of OA cartilage. The increased rate of AdipoR1-positive chondrocytes was
      twice that of AdipoR2-positive chondrocytes when compared between nonlesional and
      lesional areas. Adiponectin-stimulated OA chondrocytes showed increased total NO
      and MMP-1, -3, and -13 levels compared with nonstimulated cells. The TIMP-1 level
      was not affected. The C1-2C levels were increased by adiponectin in OA cartilage
      explant culture. AMP-activated protein kinase (AMPK) and c-Jun N-terminal kinase
      (JNK) inhibitors (compound C and SP600125) significantly suppressed adiponectin
      induced production of total NO and MMP-1, -3, and -13. Inducible NOS inhibitors
      enhanced the expression of the adiponectin-induced MMPs. CONCLUSIONS: Adiponectin
      causes matrix degradation in OA cartilage and increases MMPs and iNOS expression
      via the AMPK and JNK pathways in human OA chondrocytes. The catabolic effects of
      adiponectin may be counteracted by NO.

PMID- 21194468
TI  - Separate and combined analysis of successive dependent outcomes after breast
      conservation surgery: recurrence, metastases, second cancer and death.
AB  - BACKGROUND: In the setting of recurrent events, research studies commonly count
      only the first occurrence of an outcome in a subject. However this approach does
      not correctly reflect the natural history of the disease. The objective is to
      jointly identify prognostic factors associated with locoregional recurrences
      (LRR), contralateral breast cancer, distant metastases (DM), other primary cancer
      than breast and breast cancer death and to evaluate the correlation between these
      events. METHODS: Patients (n = 919) with a primary invasive breast cancer and
      treated in a cancer center in South-Western France with breast-conserving surgery
      from 1990 to 1994 and followed up to January 2006 were included. Several types of
      non-independent events could be observed for the same patient: a LRR, a
      contralateral breast cancer, DM, other primary cancer than breast and breast
      cancer death. Data were analyzed separately and together using a random-effects
      survival model. RESULTS: LRR represent the most frequent type of first failure
      (14.6%). The risk of any event is higher for young women (less than 40 years old)
      and in the first 10 years of follow-up after the surgery. In the combined
      analysis histological tumor size, grade, number of positive nodes, progesterone
      receptor status and treatment combination are prognostic factors of any event.
      The results show a significant dependence between these events with a
      successively increasing risk of a new event after the first and second event. The
      risk of developing a new failure is greatly increased (RR = 4.25; 95%CI: 2.51
      7.21) after developing a LRR, but also after developing DM (RR = 3.94; 95%CI:
      2.23-6.96) as compared to patients who did not develop a first event. CONCLUSION:
      We illustrated that the random effects survival model is a more satisfactory
      method to evaluate the natural history of a disease with multiple type of events.

PMID- 21194469
TI  - The effects of Tualang honey on female reproductive organs, tibia bone and
      hormonal profile in ovariectomised rats--animal model for menopause.
AB  - BACKGROUND: Honey is a highly nutritional natural product that has been widely
      used in folk medicine for a number of therapeutic purposes. We evaluated whether
      Malaysian Tualang honey (AgroMas, Malaysia) was effective in reducing menopausal
      syndrome in ovariectomised female rats; an animal model for menopause. METHODS:
      The rats were divided into two control groups and three test groups. The control
      groups were sham-operated (SH) and ovariectomised (OVX) rats. The SH and OVX
      control rats were fed on 0.5 ml of distill water. The rats in the test groups
      were fed with low dose 0.2 g/kg (THL), medium dose, 1.0 g/kg (THM) and high dose
      2.0 g/kg (THH) of Tualang honey in 0.5 ml of distill water. The administration
      was given by oral gavage once daily for 2 weeks. The reproductive organs (uterus
      and vagina), tibia bone and aorta were taken for histopathological examination
      while serum for hormonal assays. RESULTS: Administration of Tualang honey for 2
      weeks to ovariectomised rats significantly increased the weight of the uterus and
      the thickness of vaginal epithelium, restored the morphology of the tibia bones
      and reduced the body weight compared to rats in the ovariectomised group. The
      levels of estradiol and progesterone, in honey treated groups were markedly lower
      than that in the OVX group. At low doses (0.2 g/kg; THL group) of Tualang honey
      there was an increased in serum free testosterone levels compared to OVX group (P
      < 0.01). Progesterone concentrations was significantly decreased in the OVX group
      as compared to SHAM group (P < 0.05). CONCLUSIONS: Tualang honey was shown to
      have beneficial effects on menopausal (ovariectomised) rats by preventing uterine
      atrophy, increased bone density and suppression of increased body weight. Honey
      could be an alternative to HRT.

PMID- 21194470
TI  - Malaria infection and disease in an area with pyrethroid-resistant vectors in
      southern Benin.
AB  - BACKGROUND: This study aimed to investigate baseline data on malaria before the
      evaluation of new vector control strategies in an area of pyrethroid-resistance
      of vectors. The burden of malaria was estimated in terms of infection (prevalence
      and parasite density) and of clinical episodes. METHODS: Between December 2007
      and December 2008 in the health district of Ouidah-Kpomasse-Tori Bossito
      (southern Benin), a descriptive epidemiological survey of malaria was conducted.
      From 28 selected villages, seven were randomized from which a total of 440
      children aged 0 to 5 years were randomly selected. Clinical and parasitological
      information was obtained by active case detection of malaria episodes carried out
      during eight periods of six consecutive days scheduled at six weekly intervals
      and by cross-sectional surveys of asymptomatic infection. Entomological
      information was also collected. The ownership, the use and the correct use of
      long-lasting insecticide-treated nets (LLINs) were checked over weekly-survey by
      unannounced visits at home in the late evening. RESULTS: Mean parasite density in
      asymptomatic children was 586 P. falciparum asexual forms per MUL of blood (95%CI
      504-680). Pyrogenic parasite cut-off was estimated 2,000 P. falciparum asexual
      blood forms per MUL. The clinical incidence of malaria was 1.5 episodes per child
      per year (95%CI 1.2-1.9). Parasitological and clinical variables did not vary
      with season. Anopheles gambiae s.l. was the principal vector closely followed by
      Anopheles funestus. Entomological inoculation rate was 5.3 (95%CI 1.1-25.9)
      infective bites per human per year. Frequency of the L1014F kdr (West) allele was
      around 50%. Annual prevalence rate of Plasmodium falciparum asymptomatic
      infection was 21.8% (95%CI 19.1-24.4) and increased according to age. Mean rates
      of ownership and use of LLINs were 92% and 70% respectively. The only correct use
      of LLINs (63%) conferred 26% individual protection against only infection (OR =
      0.74 (95%IC 0.62-0.87), p = 0.005). CONCLUSION: The health district of Ouidah
      Kpomasse-Tori Bossito is a mesoendemic area with a moderate level of pyrethroid
      resistance of vectors. The used LLINs rate was high and only the correct use of
      LLINs was found to reduce malaria infection without influencing malaria
      morbidity.

PMID- 21194472
TI  - Enhanced structural variant and breakpoint detection using SVMerge by integration
      of multiple detection methods and local assembly.
AB  - We present a pipeline, SVMerge, to detect structural variants by integrating
      calls from several existing structural variant callers, which are then validated
      and the breakpoints refined using local de novo assembly. SVMerge is modular and
      extensible, allowing new callers to be incorporated as they become available. We
      applied SVMerge to the analysis of a HapMap trio, demonstrating enhanced
      structural variant detection, breakpoint refinement, and a lower false discovery
      rate. SVMerge can be downloaded from http://svmerge.sourceforge.net.

PMID- 21194471
TI  - Protein-enriched meal replacements do not adversely affect liver, kidney or bone
      density: an outpatient randomized controlled trial.
AB  - BACKGROUND: There is concern that recommending protein-enriched meal replacements
      as part of a weight management program could lead to changes in biomarkers of
      liver or renal function and reductions in bone density. This study was designed
      as a placebo-controlled clinical trial utilizing two isocaloric meal plans
      utilizing either a high protein-enriched (HP) or a standard protein (SP) meal
      replacement in an outpatient weight loss program. SUBJECTS/METHODS: 100 obese men
      and women over 30 years of age with a body mass index (BMI) between 27 to 40
      kg/m2 were randomized to one of two isocaloric weight loss meal plans 1). HP
      group: providing 2.2 g protein/kg of lean body mass (LBM)/day or 2). SP group:
      providing 1.1 g protein/kg LBM/day. Meal replacement (MR) was used twice daily
      (one meal, one snack) for 3 months and then once a day for 9 months. Body weight,
      lipid profiles, liver function, renal function and bone density were measured at
      baseline and 12 months. RESULTS: Seventy subjects completed the study. Both
      groups lost weight (HP -4.29 +/- 5.90 kg vs. SP -4.66 +/- 6.91 kg, p < 0.01) and
      there was no difference in weight loss observed between the groups at one year.
      There was no significant change noted in liver function [AST (HP -2.07 +/- 10.32
      U/L, p = 0.28; SP 0.27 +/- 6.67 U/L, p = 0.820), ALT (HP -1.03 +/- 10.08 U/L, p =
      0.34; SP -2.6 +/- 12.51 U/L, p = 0.24), bilirubin (HP 0.007 +/- 0.33, U/L, p =
      0.91; SP 0.07 +/- 0.24 U/L, p = 0.120), alkaline phosphatase (HP 2.00 +/- 9.07
      U/L, p = 0.240; SP -2.12 +/- 11.01 U/L, p = 0.280)], renal function [serum
      creatinine (HP 0.31 +/- 1.89 mg/dL, p = 0.380; SP -0.05 +/- 0.15 mg/dL, p =
      0.060), urea nitrogen (HP 1.33 +/- 4.68 mg/dL, p = 0.130; SP -0.24 +/- 3.03
      mg/dL, p = 0.650), 24 hour urine creatinine clearance (HP -0.02 +/- 0.16 mL/min,
      p = 0.480; SP 1.18 +/- 7.53 mL/min, p = 0.400), and calcium excretion (HP -0.41
      +/- 9.48 mg/24 hours, p = 0.830; SP -0.007 +/- 6.76 mg/24 hours, p = 0.990)] or
      in bone mineral density by DEXA (HP 0.04 +/- 0.19 g/cm2, p = 0.210; SP -0.03 +/-
      0.17 g/cm2, p = 0.320) in either group over one year. CONCLUSIONS: These studies
      demonstrate that protein-enriched meals replacements as compared to standard meal
      replacements recommended for weight management do not have adverse effects on
      routine measures of liver function, renal function or bone density at one year.

PMID- 21194474
TI  - Streptavidin-Binding Peptide (SBP)-tagged SMC2 allows single-step affinity
      fluorescence, blotting or purification of the condensin complex.
AB  - BACKGROUND: Cell biologists face the need to rapidly analyse their proteins of
      interest in order to gain insight into their function. Often protein
      purification, cellular localisation and Western blot analyses can be multi-step
      processes, where protein is lost, activity is destroyed or effective antibodies
      have not yet been generated. AIM: To develop a method that simplifies the
      critical protein analytical steps of the laboratory researcher, leading to easy,
      efficient and rapid protein purification, cellular localisation and
      quantification. RESULTS: We have tagged the SMC2 subunit of the condensin complex
      with the Streptavidin-Binding Peptide (SBP), optimising and demonstrating the
      efficacious use of this tag for performing these protein analytical steps. Based
      on silver staining, and Western analysis, SBP delivered an outstanding
      specificity and purity of the condensin complex. We also developed a rapid and
      highly specific procedure to localise SBP-tagged proteins in cells in a single
      step procedure thus bypassing the need for using antibodies. Furthermore we have
      shown that the SBP tag can be used for isolating tagged proteins from chemically
      cross-linked cell populations for capturing DNA-protein interactions.
      CONCLUSIONS: The small 38-amino acid synthetic SBP offers the potential to
      successfully perform all four critical analytical procedures as a single step and
      should have a general utility for the study of many proteins and protein
      complexes.

PMID- 21194473
TI  - Assessing interactions between the associations of common genetic susceptibility
      variants, reproductive history and body mass index with breast cancer risk in the
      breast cancer association consortium: a combined case-control study.
AB  - INTRODUCTION: Several common breast cancer genetic susceptibility variants have
      recently been identified. We aimed to determine how these variants combine with a
      subset of other known risk factors to influence breast cancer risk in white women
      of European ancestry using case-control studies participating in the Breast
      Cancer Association Consortium. METHODS: We evaluated two-way interactions between
      each of age at menarche, ever having had a live birth, number of live births, age
      at first birth and body mass index (BMI) and each of 12 single nucleotide
      polymorphisms (SNPs) (10q26-rs2981582 (FGFR2), 8q24-rs13281615, 11p15-rs3817198
      (LSP1), 5q11-rs889312 (MAP3K1), 16q12-rs3803662 (TOX3), 2q35-rs13387042, 5p12
      rs10941679 (MRPS30), 17q23-rs6504950 (COX11), 3p24-rs4973768 (SLC4A7), CASP8
      rs17468277, TGFB1-rs1982073 and ESR1-rs3020314). Interactions were tested for by
      fitting logistic regression models including per-allele and linear trend main
      effects for SNPs and risk factors, respectively, and single-parameter interaction
      terms for linear departure from independent multiplicative effects. RESULTS:
      These analyses were applied to data for up to 26,349 invasive breast cancer cases
      and up to 32,208 controls from 21 case-control studies. No statistical evidence
      of interaction was observed beyond that expected by chance. Analyses were
      repeated using data from 11 population-based studies, and results were very
      similar. CONCLUSIONS: The relative risks for breast cancer associated with the
      common susceptibility variants identified to date do not appear to vary across
      women with different reproductive histories or body mass index (BMI). The
      assumption of multiplicative combined effects for these established genetic and
      other risk factors in risk prediction models appears justified.

PMID- 21194475
TI  - Intranasal immunization with plasmid DNA encoding spike protein of SARS
      coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and
      cellular immune responses.
AB  - BACKGROUND: Immunization with the spike protein (S) of severe acute respiratory
      syndrome (SARS)-coronavirus (CoV) in mice is known to produce neutralizing
      antibodies and to prevent the infection caused by SARS-CoV. Polyethylenimine 25K
      (PEI) is a cationic polymer which effectively delivers the plasmid DNA. RESULTS:
      In the present study, the immune responses of BALB/c mice immunized via
      intranasal (i.n.) route with SARS DNA vaccine (pci-S) in a PEI/pci-S complex form
      have been examined. The size of the PEI/pci-S nanoparticles appeared to be around
      194.7 +/- 99.3 nm, and the expression of the S mRNA and protein was confirmed in
      vitro. The mice immunized with i.n. PEI/pci-S nanoparticles produced
      significantly (P < 0.05) higher S-specific IgG1 in the sera and mucosal secretory
      IgA in the lung wash than those in mice treated with pci-S alone. Compared to
      those in mice challenged with pci-S alone, the number of B220+ cells found in
      PEI/pci-S vaccinated mice was elevated. Co-stimulatory molecules (CD80 and CD86)
      and class II major histocompatibility complex molecules (I-Ad) were increased on
      CD11c+ dendritic cells in cervical lymph node from the mice after PEI/pci-S
      vaccination. The percentage of IFN-gamma-, TNF-alpha- and IL-2-producing cells
      were higher in PEI/pci-S vaccinated mice than in control mice. CONCLUSION: These
      results showed that intranasal immunization with PEI/pci-S nanoparticles induce
      antigen specific humoral and cellular immune responses.

PMID- 21194476
TI  - Leaf-cutting ant fungi produce cell wall degrading pectinase complexes
      reminiscent of phytopathogenic fungi.
AB  - BACKGROUND: Leaf-cutting (attine) ants use their own fecal material to manure
      fungus gardens, which consist of leaf material overgrown by hyphal threads of the
      basidiomycete fungus Leucocoprinus gongylophorus that lives in symbiosis with the
      ants. Previous studies have suggested that the fecal droplets contain proteins
      that are produced by the fungal symbiont to pass unharmed through the digestive
      system of the ants, so they can enhance new fungus garden growth. RESULTS: We
      tested this hypothesis by using proteomics methods to determine the gene
      sequences of fecal proteins in Acromyrmex echinatior leaf-cutting ants. Seven
      (21%) of the 33 identified proteins were pectinolytic enzymes that originated
      from the fungal symbiont and which were still active in the fecal droplets
      produced by the ants. We show that these enzymes are found in the fecal material
      only when the ants had access to fungus garden food, and we used quantitative
      polymerase chain reaction analysis to show that the expression of six of these
      enzyme genes was substantially upregulated in the fungal gongylidia. These unique
      structures serve as food for the ants and are produced only by the evolutionarily
      advanced garden symbionts of higher attine ants, but not by the fungi reared by
      the basal lineages of this ant clade. CONCLUSIONS: Pectinolytic enzymes produced
      in the gongylidia of the fungal symbiont are ingested but not digested by
      Acromyrmex leaf-cutting ants so that they end up in the fecal fluid and become
      mixed with new garden substrate. Substantial quantities of pectinolytic enzymes
      are typically found in pathogenic fungi that attack live plant tissue, where they
      are known to breach the cell walls to allow the fungal mycelium access to the
      cell contents. As the leaf-cutting ant symbionts are derived from fungal clades
      that decompose dead plant material, our results suggest that their pectinolytic
      enzymes represent secondarily evolved adaptations that are convergent to those
      normally found in phytopathogens.

PMID- 21194477
TI  - Condylar volume and surface in Caucasian young adult subjects.
AB  - BACKGROUND: There have been no quantitative standards for volumetric and surface
      measurements of the mandibular condyle in Caucasian population. However, the
      recently developed cone-beam computed tomography (CBCT) system allows measurement
      of these parameters with high accuracy. METHODS: CBCT was used to measure the
      condylar volume, surface and the volume to surface ratio, called the Morphometric
      Index (MI), of 300 temporo-mandibular joints (TMJ) in 150 Caucasian young adult
      subjects, with varied malocclusions, without pain or dysfunction of TMJs.
      RESULTS: The condylar volume was 691.26 +/- 54.52 mm3 in males and 669.65 +/-
      58.80 mm3 in, and was significantly higher (p< 0.001) in the males. The same was
      observed for the condylar surface, although without statistical significance
      (406.02 +/- 55.22 mm2 in males and 394.77 +/- 60.73 mm2 in females).Furthermore,
      the condylar volume (693.61 +/- 62.82 mm3 ) in the right TMJ was significantly
      higher than in the left (666.99 +/- 48.67 mm3, p < 0.001) as was the condylar
      surface (411.24 +/- 57.99 mm2 in the right TMJ and 389.41 +/- 56.63 mm2 in the
      left TMJ; t = 3.29; p < 0.01). The MI is 1.72 +/- 0.17 for the whole sample, with
      no significant difference between males and females or the right and left sides.
      CONCLUSION: These data from temporomandibular joints of patients without pain or
      clinical dysfunction might serve as examples of normal TMJ's in the general
      population not seeking orthodontic care.

PMID- 21194478
TI  - ESR and NMR studies provide evidence that phosphatidyl glycerol specifically
      interacts with poxvirus membranes.
AB  - BACKGROUND: The lung would be the first organ targeted in case of the use of
      Variola virus (the causative agent of smallpox) as a bioweapon. Pulmonary
      surfactant composed of lipids (90%) and proteins (10%) is considered the major
      physiological barrier against airborne pathogens. The principle phospholipid
      components of lung surfactant were examined in an in vitro model to characterize
      their interactions with VACV, a surrogate for variola virus. One of them,
      Dipalmitoyl phosphatidylglycerol (DPPG), was recently shown to inhibit VACV cell
      infection. RESULTS: The interactions of poxvirus particles from the Western
      Reserve strain (VACV-WR) and the Lister strain (VACV-List) with model membranes
      for pulmonary surfactant phospholipids, in particular DPPG, were studied by
      Electron Spin Resonance (ESR) and proton Nuclear Magnetic Resonance (1H-NMR). ESR
      experiments showed that DPPG exhibits specific interactions with both viruses,
      while NMR experiments allowed us to deduce its stoichiometry and to propose a
      model for the mechanism of interaction at the molecular level. CONCLUSIONS: These
      results confirm the ability of DPPG to strongly bind to VACV and suggest that
      similar interactions occur with variola virus. Similar studies of the
      interactions between lipids and other airborne pathogens are warranted.

PMID- 21194479
TI  - Nutrient intakes of rural Tibetan mothers: a cross-sectional survey.
AB  - BACKGROUND: Tibetan food intake is influenced by the region's high altitude and
      unique culture. Few published studies of nutrient intakes among Tibetan women are
      available. The present study of Tibetan mothers with young children explores
      dietary patterns, nutrient intakes, and differences between socio-demographic
      groups. METHODS: A cross-sectional survey of 386 women with a child aged less
      than 24 months was conducted in rural areas surrounding Lhasa, Tibet. All
      participants were recruited using simple random sampling and were interviewed
      face-to-face by trained investigators. Dietary information was collected via a
      food frequency questionnaire. Nutrient intakes were calculated using food
      composition tables. Non-parametric tests were used to compare nutrient intakes
      according to socio-demographic variables, and to compare results with the 2002
      Chinese National Nutrition and Health Survey (2002 NNHS) and dietary reference
      intakes (DRIs). RESULTS: Median intakes of energy (p < 0.001), protein (p <
      0.001), fat (p < 0.001), vitamin A (p < 0.001), vitamin B1 (p < 0.001), vitamin
      B2 (p < 0.001), vitamin C (p < 0.001), and vitamin E (p < 0.001) were lower than
      the average levels reported in 2002 NNHS. The median intakes of calcium (517
      mg/d, p < 0.001), iron (35 mg/d, p < 0.001), and zinc (17.3 mg/d, p < 0.001) were
      higher than the average levels in 2002 NNHS. The highest education subgroup had
      significantly higher intakes of vitamins A and C than the lowest education
      subgroup. CONCLUSION: Although the diet of Tibetan mothers with young children
      has been partially influenced by other factors, their dietary patterns are still
      mostly composed of Tibetan traditional foods. Compared with the 2002 NNHS,
      Tibetan women with young children appear to have insufficient intakes of many
      nutrients, which will affect their nutritional status.

PMID- 21194480
TI  - Cerebrospinal fluid lactate concentration to distinguish bacterial from aseptic
      meningitis: a systemic review and meta-analysis.
AB  - INTRODUCTION: Making a differential diagnosis between bacterial meningitis and
      aseptic meningitis is a critical clinical problem. The utility of a cerebrospinal
      fluid (CSF) lactate assay for this purpose has been debated and is not yet
      routinely clinically performed. To adequately evaluate this assay, a systematic
      review and meta-analysis of studies of the CSF lactate concentration as a marker
      for both bacterial meningitis and aseptic meningitis was performed. METHODS:
      Electronic searches in PubMed, Scopus, the MEDION database and the Cochrane
      Library were conducted to identify relevant articles published before March 2009.
      A manual search of reference lists from selected articles was also conducted. Two
      reviewers independently selected relevant articles and extracted data on study
      characteristics, quality and accuracy. RESULTS: Twenty-five articles were
      identified that met the eligibility criteria. Diagnostic odds ratios were
      considerably homogenous (Chi-square P = 0.1009, I(2) = 27.6%), and the
      homogeneity was further confirmed by a Galbraith plot and meta-regression
      analysis using several covariates. The symmetrical summary receiver-operator
      characteristic curve (SROC), fitted using the Moses-Shapiro-Littenberg method,
      was positioned near the upper left corner of the SROC curve. The Q value and area
      under the curve were 0.9451 and 0.9840, respectively, indicating excellent
      accuracy. The diagnostic accuracy of the CSF lactate concentration was higher
      than those of other four conventional markers (CSF glucose, CSF/plasma glucose
      quotient, CSF protein, and CSF total number of leukocytes) using a head to head
      meta-analysis of the 25 included studies. CONCLUSIONS: To distinguish bacterial
      meningitis from aseptic meningitis, CSF lactate is a good single indicator and a
      better marker compared to other conventional markers.

PMID- 21194481
TI  - Intraplaque hemorrhage is associated with higher structural stresses in human
      atherosclerotic plaques: an in vivo MRI-based 3D fluid-structure interaction
      study.
AB  - BACKGROUND: Studies using medical images have shown that intraplaque hemorrhage
      may accelerate plaque progression and may produce a stimulus for atherosclerosis
      development by increasing lipid core and plaque volume and creating new
      destabilizing factors. Image-based 3D computational models with fluid-structure
      interactions (FSI) will be used to perform plaque mechanical analysis and
      investigate possible associations between intraplaque hemorrhage and both plaque
      wall stress (PWS) and flow shear stress (FSS). METHODS: In vivo MRI data of
      carotid plaques from 5 patients with intraplaque hemorrhage confirmed by
      histology were acquired. 3D multi-component FSI models were constructed for each
      plaque to obtain mechanical stresses. Plaque Wall Stress (PWS) and Flow Shear
      Stress (FSS) were extracted from all nodal points on the lumen surface of each
      plaque for analysis. RESULTS: The mean PWS value from all hemorrhage nodes of the
      5 plaques combined was higher than that from non-hemorrhage nodes (75.6 versus
      68.1 kPa, P = 0.0003). The mean PWS values from hemorrhage nodes for each of the
      5 plaques were all significantly higher (5 out of 5) than those from non
      hemorrhage nodes (P < 0.05). The mean FSS value from all hemorrhage nodes of the
      5 plaques combined was 30.4% higher than that from all non-hemorrhage nodes (15.0
      versus 11.5 dyn/cm2, P = 0.0002). However, the mean flow shear stress values from
      individual cases showed mixed results: only one out of five plaques showed mean
      FSS value from hemorrhage nodes was higher than that from non-hemorrhage nodes;
      three out of five plaques showed that their mean FSS values from hemorrhage nodes
      were lower than those from non-hemorrhage nodes; and one plaque showed that the
      difference had no statistical significance. CONCLUSION: The results of this study
      suggested that intraplaque hemorrhage nodes were associated with higher plaque
      wall stresses. Compared to flow shear stress, plaque wall stress has a better
      correlation with plaque component feature (hemorrhage) linked to plaque
      progression and vulnerability. With further validation, plaque stress analysis
      may provide additional stress indicators for image-based vulnerability
      assessment.

PMID- 21194482
TI  - Epstein-Barr virus-specific methylation of human genes in gastric cancer cells.
AB  - BACKGROUND: Epstein-Barr Virus (EBV) is found in 10% of all gastric
      adenocarcinomas but its role in tumor development and maintenance remains
      unclear. The objective of this study was to examine EBV-mediated dysregulation of
      cellular factors implicated in gastric carcinogenesis. METHODS: Gene expression
      patterns were examined in EBV-negative and EBV-positive AGS gastric epithelial
      cells using a low density microarray, reverse transcription PCR, histochemical
      stains, and methylation-specific DNA sequencing. Expression of PTGS2 (COX2) was
      measured in AGS cells and in primary gastric adenocarcinoma tissues. RESULTS: In
      array studies, nearly half of the 96 human genes tested, representing 15
      different cancer-related signal transduction pathways, were dysregulated after
      EBV infection. Reverse transcription PCR confirmed significant impact on factors
      having diverse functions such as cell cycle regulation (IGFBP3, CDKN2A, CCND1,
      HSP70, ID2, ID4), DNA repair (BRCA1, TFF1), cell adhesion (ICAM1), inflammation
      (COX2), and angiogenesis (HIF1A). Demethylation using 5-aza-2'-deoxycytidine
      reversed the EBV-mediated dysregulation for all 11 genes listed here. For some
      promoter sequences, CpG island methylation and demethylation occurred in an EBV
      specific pattern as shown by bisulfite DNA sequencing. Immunohistochemistry was
      less sensitive than was western blot for detecting downregulation of COX2 upon
      EBV infection. Virus-related dysregulation of COX2 levels in vitro was not
      recapitulated in vivo among naturally infected gastric cancer tissues.
      CONCLUSIONS: EBV alters human gene expression in ways that could contribute to
      the unique pathobiology of virus-associated cancer. Furthermore, the frequency
      and reversability of methylation-related transcriptional alterations suggest that
      demethylating agents have therapeutic potential for managing EBV-related
      carcinoma.

PMID- 21194483
TI  - Smed454 dataset: unravelling the transcriptome of Schmidtea mediterranea.
AB  - BACKGROUND: Freshwater planarians are an attractive model for regeneration and
      stem cell research and have become a promising tool in the field of regenerative
      medicine. With the availability of a sequenced planarian genome, the recent
      application of modern genetic and high-throughput tools has resulted in
      revitalized interest in these animals, long known for their amazing regenerative
      capabilities, which enable them to regrow even a new head after decapitation.
      However, a detailed description of the planarian transcriptome is essential for
      future investigation into regenerative processes using planarians as a model
      system. RESULTS: In order to complement and improve existing gene annotations, we
      used a 454 pyrosequencing approach to analyze the transcriptome of the planarian
      species Schmidtea mediterranea Altogether, 598,435 454-sequencing reads, with an
      average length of 327 bp, were assembled together with the ~10,000 sequences of
      the S. mediterranea UniGene set using different similarity cutoffs. The assembly
      was then mapped onto the current genome data. Remarkably, our Smed454 dataset
      contains more than 3 million novel transcribed nucleotides sequenced for the
      first time. A descriptive analysis of planarian splice sites was conducted on
      those Smed454 contigs that mapped univocally to the current genome assembly.
      Sequence analysis allowed us to identify genes encoding putative proteins with
      defined structural properties, such as transmembrane domains. Moreover, we
      annotated the Smed454 dataset using Gene Ontology, and identified putative
      homologues of several gene families that may play a key role during regeneration,
      such as neurotransmitter and hormone receptors, homeobox-containing genes, and
      genes related to eye function. CONCLUSIONS: We report the first planarian
      transcript dataset, Smed454, as an open resource tool that can be accessed via a
      web interface. Smed454 contains significant novel sequence information about most
      expressed genes of S. mediterranea. Analysis of the annotated data promises to
      contribute to identification of gene families poorly characterized at a
      functional level. The Smed454 transcriptome data will assist in the molecular
      characterization of S. mediterranea as a model organism, which will be useful to
      a broad scientific community.

PMID- 21194484
TI  - Knowledge and information needs of young people with epilepsy and their parents:
      Mixed-method systematic review.
AB  - BACKGROUND: Young people with neurological impairments such as epilepsy are known
      to receive less adequate services compared to young people with other long-term
      conditions. The time (age 13-19 years) around transition to adult services is
      particularly important in facilitating young people's self-care and ongoing
      management. There are epilepsy specific, biological and psycho-social factors
      that act as barriers and enablers to information exchange and nurturing of self
      care practices. Review objectives were to identify what is known to be effective
      in delivering information to young people age 13-19 years with epilepsy and their
      parents, to describe their experiences of information exchange in healthcare
      contexts, and to identify factors influencing positive and negative healthcare
      communication. METHODS: The Evidence for Policy and Practice Information
      Coordinating Centre systematic mixed-method approach was adapted to locate,
      appraise, extract and synthesise evidence. We used Ley's cognitive hypothetical
      model of communication and subsequently developed a theoretical framework
      explaining information exchange in healthcare contexts. RESULTS: Young people and
      parents believed that healthcare professionals were only interested in medical
      management. Young people felt that discussions about their epilepsy primarily
      occurred between professionals and parents. Epilepsy information that young
      people obtained from parents or from their own efforts increased the risk of
      epilepsy misconceptions. Accurate epilepsy knowledge aided psychosocial
      adjustment. There is some evidence that interventions, when delivered in a
      structured psycho-educational, age appropriate way, increased young people's
      epilepsy knowledge, with positive trend to improving quality of life. We used
      mainly qualitative and mixed-method evidence to develop a theoretical framework
      explaining information exchange in clinical encounters. CONCLUSIONS: There is a
      paucity of evidence reporting effective interventions, and the most effective
      ways of delivering information/education in healthcare contexts. No studies
      indicated if improvement was sustained over time and whether increased knowledge
      was effective in improving in self-care. Current models of facilitating
      information exchange and self-care around transition are not working well. There
      is an urgent need for further studies to develop and evaluate interventions to
      facilitate successful information exchange, and follow young people over time to
      see if interventions showing early promise are effective in the medium to long
      term.

PMID- 21194485
TI  - Lack of alpha8 integrin leads to morphological changes in renal mesangial cells,
      but not in vascular smooth muscle cells.
AB  - BACKGROUND: Extracellular matrix receptors of the integrin family are known to
      regulate cell adhesion, shape and functions. The alpha8 integrin chain is
      expressed in glomerular mesangial cells and in vascular smooth muscle cells. Mice
      deficient for alpha8 integrin have structural alterations in glomeruli but not in
      renal arteries. For this reason we hypothesized that mesangial cells and vascular
      smooth muscle cells differ in their respective capacity to compensate for the
      lack of alpha8 integrin. RESULTS: Wild type and alpha8 integrin-deficient
      mesangial cells varied markedly in cell morphology and expression or localization
      of cytoskeletal molecules. In alpha8 integrin-deficient mesangial cells alpha
      smooth muscle actin and CTGF were downregulated. In contrast, there were no
      comparable differences between alpha8 integrin-deficient and wild type vascular
      smooth muscle cells. Expression patterns of integrins were altered in alpha8
      integrin-deficient mesangial cells compared to wild type mesangial cells,
      displaying a prominent overexpression of alpha2 and alpha6 integrins, while
      expression patterns of the these integrins were not different between wild type
      and alpha8 integrin-deficient vascular smooth muscle cells, respectively. Cell
      proliferation was augmented in alpha8 integrin-deficient mesangial cells, but not
      in vascular smooth muscle cells, compared to wild type cells. CONCLUSIONS: Our
      findings suggest that alpha8 integrin deficiency has differential effects in
      mesangial cells and vascular smooth muscle cells. While the phenotype of vascular
      smooth muscle cells lacking alpha8 integrin is not altered, mesangial cells
      lacking alpha8 integrin differ considerably from wild type mesangial cells which
      might be a consequence of compensatory changes in the expression patterns of
      other integrins. This could result in glomerular changes in alpha8 integrin
      deficient mice, while the vasculature is not affected in these mice.

PMID- 21194486
TI  - Household food insecurity and symptoms of neurologic disorder in Ethiopia: an
      observational analysis.
AB  - BACKGROUND: Food insecurity (FI) has been shown to be associated with poor health
      both in developing and developed countries. Little is known about the relation
      between FI and neurological disorder. We assessed the relation between FI and
      risk for neurologic symptoms in southwest Ethiopia. METHODS: Data about food
      security, gender, age, household assets, and self-reported neurologic symptoms
      were collected from a representative, community-based sample of adults (N = 900)
      in Jimma Zone, Ethiopia. We calculated univariate statistics and used bivariate
      chi-square tests and multivariate logistic regression models to assess the
      relation between FI and risk of neurologic symptoms including seizures, extremity
      weakness, extremity numbness, tremors/ataxia, aphasia, carpal tunnel syndrome,
      vision dysfunction, and spinal pain. RESULTS: In separate multivariate models by
      outcome and gender, adjusting for age and household socioeconomic status, severe
      FI was associated with higher odds of seizures, movement abnormalities, carpal
      tunnel, vision dysfunction, spinal pain, and comorbid disorders among women.
      Severe FI was associated with higher odds of seizures, extremity numbness,
      movement abnormalities, difficulty speaking, carpal tunnel, vision dysfunction,
      and comorbid disorders among men. CONCLUSION: We found that FI was associated
      with symptoms of neurologic disorder. Given the cross-sectional nature of our
      study, the directionality of these associations is unclear. Future research
      should assess causal mechanisms relating FI to neurologic symptoms in sub-Saharan
      Africa.

PMID- 21194487
TI  - Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small
      cell lung cancer patients who benefited from prior effective gefitinib therapy: a
      retrospective analysis.
AB  - BACKGROUND: Gefitinib was the first epidermal growth factor receptor-tyrosine
      kinase inhibitor (EGFR-TKI) approved for the treatment of advanced non-small cell
      lung cancer (NSCLC). Few treatment options are available for NSCLC patients who
      have responded to gefitinib treatment and demonstrated tumor progression. The
      present study was conducted to evaluate the efficacy and toxicity of the 2(nd)
      EGFR-TKI administration. METHODS: We retrospectively analyzed 11 patients who had
      obtained a partial response (PR) or stable disease (SD) with gefitinib treatment
      and were re-treated with EGFR-TKI after failure of the initial gefitinib
      treatment. RESULTS: Three patients (27%) were treated with gefitinib as the 2(nd)
      EGFR-TKI, and 8 patients (73%) received erlotinib. Only one patient (9%) showed
      PR, 7 (64%) achieved SD, and 3 (27%) had progressive disease. The disease control
      rate was 73% (95% CI, 43% - 91%) and the median progression-free survival was 3.4
      months (95% CI, 2 - 5.2). The median overall survival from the beginning of the
      2(nd) EGFR-TKI and from diagnosis were 7.3 months (95% CI, 2.7 - 13) and 36.7
      months (95% CI, 23.6 - 43.9), respectively. No statistical differences in PFS or
      OS were observed between gefitinib and erlotinib as the 2(nd) EGFR-TKI (PFS, P =
      0.23 and OS, P = 0.052). The toxicities associated with the 2(nd) EGFR-TKI were
      generally acceptable and comparable to those observed for the initial gefitinib
      therapy. CONCLUSIONS: Our results indicate that a 2(nd) EGFR-TKI treatment can be
      an effective treatment option for gefitinib responders.

PMID- 21194488
TI  - Mannan-binding lectin regulates dendritic cell maturation and cytokine production
      induced by lipopolysaccharide.
AB  - BACKGROUND: Mannan-binding lectin (MBL) is a pattern-recognition molecule present
      in serum, which is involved in the innate immune defense by activating complement
      and promoting opsonophagocytosis. Dendritic cells (DCs) are professional antigen
      presenting cells (APCs) that are crucial for the initiation of adaptive immunity.
      Lipopolysaccharide (LPS) has been shown to be a strong activator of the
      inflammatory response and immune regulation. We first examined whether MBL
      modulated LPS-induced cellular responses, then investigated possible mechanisms
      of its inhibitory effect. RESULTS: MBL at higher concentrations (10-20 MUg/ml)
      significantly attenuated LPS-induced maturation of monocyte-derived DCs (MDCs)
      and production of proinflammatory cytokines (e.g., IL-12 and TNF-alpha), and
      inhibited their ability to activate allogeneic T lymphocytes. It bound to
      immature MDCs at physiological calcium concentrations, and was optimal at
      supraphysiological calcium concentrations. MBL also bound directly to immature
      MDCs and attenuated the binding of LPS to the cell surfaces, resulting in
      decreased LPS-induced nuclear factor-kappaB (NF-kappaB) activity in these cells.
      CONCLUSION: All these data suggest that MBL could affect the functions of DCs by
      modifying LPS-induced cellular responses. This study supports an important role
      for MBL in the regulation of adaptive immune responses and inflammatory
      responses.

PMID- 21194489
TI  - Metabolomic correlation-network modules in Arabidopsis based on a graph
      clustering approach.
AB  - BACKGROUND: Deciphering the metabolome is essential for a better understanding of
      the cellular metabolism as a system. Typical metabolomics data show a few but
      significant correlations among metabolite levels when data sampling is repeated
      across individuals grown under strictly controlled conditions. Although several
      studies have assessed topologies in metabolomic correlation networks, it remains
      unclear whether highly connected metabolites in these networks have specific
      functions in known tissue- and/or genotype-dependent biochemical pathways.
      RESULTS: In our study of metabolite profiles we subjected root tissues to gas
      chromatography-time-of-flight/mass spectrometry (GC-TOF/MS) and used published
      information on the aerial parts of 3 Arabidopsis genotypes, Col-0 wild-type,
      methionine over-accumulation 1 (mto1), and transparent testa4 (tt4) to compare
      systematically the metabolomic correlations in samples of roots and aerial parts.
      We then applied graph clustering to the constructed correlation networks to
      extract densely connected metabolites and evaluated the clusters by biochemical
      pathway enrichment analysis. We found that the number of significant correlations
      varied by tissue and genotype and that the obtained clusters were significantly
      enriched for metabolites included in biochemical pathways. CONCLUSIONS: We
      demonstrate that the graph-clustering approach identifies tissue- and/or genotype
      dependent metabolomic clusters related to the biochemical pathway. Metabolomic
      correlations complement information about changes in mean metabolite levels and
      may help to elucidate the organization of metabolically functional modules.

PMID- 21194490
TI  - Identification of genes differentially expressed during interaction of Mexican
      lime tree infected with "Candidatus Phytoplasma aurantifolia".
AB  - BACKGROUND: "Candidatus Phytoplasma aurantifolia", is the causative agent of
      witches' broom disease in Mexican lime trees (Citrus aurantifolia L.), and is
      responsible for major losses of Mexican lime trees in Southern Iran and Oman. The
      pathogen is strictly biotrophic, and thus is completely dependent on living host
      cells for its survival. The molecular basis of compatibility and disease
      development in this system is poorly understood. Therefore, we have applied a
      cDNA- amplified fragment length polymorphism (AFLP) approach to analyze gene
      expression in Mexican lime trees infected by "Ca. Phytoplasma aurantifolia".
      RESULTS: We carried out cDNA-AFLP analysis on grafted infected Mexican lime trees
      of the susceptible cultivar at the representative symptoms stage. Selective
      amplifications with 43 primer combinations allowed the visualisation of 55
      transcript-derived fragments that were expressed differentially between infected
      and non-infected leaves. We sequenced 51 fragments, 36 of which were identified
      as lime tree transcripts after homology searching. Of the 36 genes, 70.5% were
      down-regulated during infection and could be classified into various functional
      groups. We showed that Mexican lime tree genes that were homologous to known
      resistance genes tended to be repressed in response to infection. These included
      the genes for modifier of snc1 and autophagy protein 5. Furthermore, down
      regulation of genes involved in metabolism, transcription, transport and
      cytoskeleton was observed, which included the genes for formin, importin beta 3,
      transducin, L-asparaginase, glycerophosphoryl diester phosphodiesterase, and RNA
      polymerase beta. In contrast, genes that encoded a proline-rich protein,
      ubiquitin-protein ligase, phosphatidyl glycerol specific phospholipase C-like,
      and serine/threonine-protein kinase were up-regulated during the infection.
      CONCLUSION: The present study identifies a number of candidate genes that might
      be involved in the interaction of Mexican lime trees with "Candidatus Phytoplasma
      aurantifolia". These results should help to elucidate the molecular basis of the
      infection process and to identify genes that could be targeted to increase plant
      resistance and inhibit the growth and reproduction of the pathogen.

PMID- 21194491
TI  - Phylogenomic reconstruction of lactic acid bacteria: an update.
AB  - BACKGROUND: Lactic acid bacteria (LAB) are important in the food industry for the
      production of fermented food products and in human health as commensals in the
      gut. However, the phylogenetic relationships among LAB species remain under
      intensive debate owing to disagreements among different data sets. RESULTS: We
      performed a phylogenetic analysis of LAB species based on 232 genes from 28 LAB
      genome sequences. Regardless of the tree-building methods used, combined analyses
      yielded an identical, well-resolved tree topology with strong supports for all
      nodes. The LAB species examined were divided into two groups. Group 1 included
      families Enterococcaceae and Streptococcaceae. Group 2 included families
      Lactobacillaceae and Leuconostocaceae. Within Group 2, the LAB species were
      divided into two clades. One clade comprised of the acidophilus complex of genus
      Lactobacillus and two other species, Lb. sakei and Lb. casei. In the acidophilus
      complex, Lb. delbrueckii separated first, while Lb. acidophilus/Lb. helveticus
      and Lb. gasseri/Lb. johnsonii were clustered into a sister group. The other clade
      within Group 2 consisted of the salivarius subgroup, including five species, Lb.
      salivarius, Lb. plantarum, Lb. brevis, Lb. reuteri, Lb. fermentum, and the genera
      Pediococcus, Oenococcus, and Leuconostoc. In this clade, Lb. salivarius was
      positioned most basally, followed by two clusters, one corresponding to Lb.
      plantarum/Lb. brevis pair and Pediococcus, and the other including
      Oenococcus/Leuconostoc pair and Lb. reuteri/Lb. fermentum pair. In addition,
      phylogenetic utility of the 232 genes was analyzed to identify those that may be
      more useful than others. The genes identified as useful were related to
      translation and ribosomal structure and biogenesis (TRSB), and a three-gene set
      comprising genes encoding ultra-violet resistance protein B (uvrB), DNA
      polymerase III (polC) and penicillin binding protein 2B (pbpB). CONCLUSIONS: Our
      phylogenomic analyses provide important insights into the evolution and
      diversification of LAB species, and also revealed the phylogenetic utility of
      several genes. We infer that the occurrence of multiple, independent adaptation
      events in LAB species, have resulted in their occupation of various habitats.
      Further analyses of more genes from additional, representative LAB species are
      needed to reveal the molecular mechanisms underlying adaptation of LAB species to
      various environmental niches.

PMID- 21194492
TI  - An assessment of self-reported physical activity instruments in young people for
      population surveillance: Project ALPHA.
AB  - BACKGROUND: The assessment of physical activity is an essential part of
      understanding patterns and influences of behaviour, designing interventions, and
      undertaking population surveillance and monitoring, but it is particularly
      problematic when using self-report instruments with young people. This study
      reviewed available self-report physical activity instruments developed for use
      with children and adolescents to assess their suitability and feasibility for use
      in population surveillance systems, particularly in Europe. METHODS: Systematic
      searches and review, supplemented by expert panel assessment. RESULTS: Papers
      (n=437) were assessed as potentially relevant; 89 physical activity measures were
      identified with 20 activity-based measures receiving detailed assessment. Three
      received support from the majority of the expert group: Physical Activity
      Questionnaire for Children/Adolescents (PAQ-C/PAQ-A), Youth Risk Behaviour
      Surveillance Survey (YRBS), and the Teen Health Survey. CONCLUSIONS: Population
      surveillance of youth physical activity is strongly recommended and those
      involved in developing and undertaking this task should consider the three
      identified shortlisted instruments and evaluate their appropriateness for
      application within their national context. Further development and testing of
      measures suitable for population surveillance with young people is required.

PMID- 21194493
TI  - Expression of plakophilins (PKP1, PKP2, and PKP3) in gastric cancers.
AB  - BACKGROUND: The importance of cell-cell junction proteins (including armadillo
      proteins) in tumor biology is known, but limited with regard to plakophilins. We
      explored the relationship between plakophilins (PKP1, PKP2, PKP3) to gastric
      cancer via immunohistochemical techniques. METHODS: We compared the
      immunohistochemistry of PKPs in 34 gastric adenocarcinomas and 20 normal gastric
      tissues. RESULTS: In gastric cancer, PKP1 expression was unchanged but PKP2 and
      PKP3 were significantly decreased as compared to normal controls. There was no
      observable clinical association with PKP1 or PKP2 expression; however, low PKP3
      level and poor prognosis appeared to correlate with regards to node number and
      tumor stage. The mean disease-free survival (DFS) was 38 +/- 3 months (range: 32 
      44) and mean overall survival (OS) 42 +/- 4 months (range: 38 - 50). Decreased
      PKP2 appeared to negatively impact DFS. CONCLUSION: Decreased PKP2 and PKP3 may
      be early prognostic markers and loss of PKP3 expression during gastric carcinoma
      progression may indicate an invasive phenotype.

PMID- 21194494
TI  - Comparison of ankle and subtalar joint complex range of motion during barefoot
      walking and walking in Masai Barefoot Technology sandals.
AB  - BACKGROUND: Masai Barefoot Technology (MBT, Switzerland) produce footwear which
      they claim simulate walking barefoot on soft undulating ground. This paper
      reports an investigation into the effect of MBT sandals on the motion of the
      ankle and subtalar joint complex during walking. METHODS: Range of motion data
      was collected in the sagittal, frontal and transverse plane from the ankle and
      subtalar joint complex from 32 asymptomatic subjects using the CODA MPX30 motion
      analysis system during both barefoot walking and walking in the MBT sandal. Shod
      and un-shod data were compared using the Wilcoxon signed ranks test. RESULTS: A
      significantly greater range of motion in the frontal and sagittal planes was
      recorded when walking in the MBT sandal (p = 0.031, and p = 0.015 respectively).
      In the transverse plane, no significant difference was found (p = 0.470).
      CONCLUSIONS: MBT sandals increase the range of motion of the ankle and subtalar
      joint complex in the frontal and sagittal planes. MBT footwear could therefore
      have a role to play in the management of musculoskeletal disorders where an
      increase in frontal and sagittal plane range of motion is desirable.

PMID- 21194495
TI  - An unbiased metagenomic search for infectious agents using monozygotic twins
      discordant for chronic fatigue.
AB  - BACKGROUND: Chronic fatigue syndrome is an idiopathic syndrome widely suspected
      of having an infectious or immune etiology. We applied an unbiased metagenomic
      approach to try to identify known or novel infectious agents in the serum of 45
      cases with chronic fatigue syndrome or idiopathic chronic fatigue. Controls were
      the unaffected monozygotic co-twins of cases, and serum samples were obtained at
      the same place and time. RESULTS: No novel DNA or RNA viral signatures were
      confidently identified. Four affected twins and no unaffected twins evidenced
      viremia with GB virus C (8.9% vs. 0%, p = 0.019), and one affected twin had
      previously undetected hepatitis C viremia. An excess of GB virus C viremia in
      cases with chronic fatigue requires confirmation. CONCLUSIONS: Current, impairing
      chronic fatigue was not robustly associated with viremia detectable in serum.

PMID- 21194496
TI  - ALGOS: the development of a randomized controlled trial testing a case management
      algorithm designed to reduce suicide risk among suicide attempters.
AB  - BACKGROUND: Suicide attempts (SA) constitute a serious clinical problem. People
      who attempt suicide are at high risk of further repetition. However, no
      interventions have been shown to be effective in reducing repetition in this
      group of patients. METHODS/DESIGN: Multicentre randomized controlled trial. We
      examine the effectiveness of "ALGOS algorithm": an intervention based in a
      decisional tree of contact type which aims at reducing the incidence of repeated
      suicide attempt during 6 months. This algorithm of case management comprises the
      two strategies of intervention that showed a significant reduction in the number
      of SA repeaters: systematic telephone contact (ineffective in first-attempters)
      and "Crisis card" (effective only in first-attempters). Participants who are lost
      from contact and those refusing healthcare, can then benefit from "short letters"
      or "postcards". DISCUSSION: ALGOS algorithm is easily reproducible and
      inexpensive intervention that will supply the guidelines for assessment and
      management of a population sometimes in difficulties with healthcare compliance.
      Furthermore, it will target some of these subgroups of patients by providing
      specific interventions for optimizing the benefits of case management strategy.

PMID- 21194497
TI  - Use and knowledge of the razor-billed curassow pauxi tuberosa (spix, 1825)
      (galliformes, cracidae) by a riverine community of the oriental amazonia, brazil.
AB  - In the Amazonian basin, the human populations that traditionally inhabit the
      forest use its natural resources in various ways. One example is the local fauna
      which, among several other uses, is an important source of protein. The general
      aim of our study was to investigate the importance of hunting to the lives of the
      Amazonian riverine communities and to identify the multiple uses and knowledge
      about the hunted animals. In this article we focused the study on the razor
      billed curassow Pauxi tuberosa, a Cracidae of significant value to the studied
      community. The investigation was conducted in the "Riozinho do Anfrisio
      Extractive Reserve", a Brazilian Conservation Unit located at the Altamira
      municipality, in the state of Para. We used an ethnoecological approach, which
      included participant observation and semi-structured interviews. Our results show
      that the razor-billed curassow is used by the "Riozinho do Anfrisio" local
      population mainly as food, but it also fulfils secondary functions, with the
      feathers being used as a domestic tool and as magic-religious symbol, some organs
      as traditional medicine, and some chicks even being raised as pets. Our study
      also revealed that the traditional ecological knowledge of the riverines about
      their environment is considerably large, and that the local biodiversity provides
      various ecosystem services.

PMID- 21194498
TI  - Smoking, longer disease duration and absence of rhinosinusitis are related to
      fixed airway obstruction in Koreans with severe asthma: findings from the COREA
      study.
AB  - BACKGROUND: The clinical manifestations of severe asthma are heterogeneous. Some
      individuals with severe asthma develop irreversible fixed airway obstruction,
      which is associated with poor outcomes. We therefore investigated the factors
      associated with fixed airway obstruction in Korean patients with severe asthma.
      METHODS: Severe asthma patients from a Korean adult asthma cohort were divided
      into two groups according to the results of serial pulmonary function tests. One
      group had fixed airway obstruction (FAO) [forced expiratory volume in 1 second
      (FEV1)/forced vital capacity (FVC) ratio < 0.7, n = 119] and the other had
      reversible airway obstruction (RAO) [FEV1/FVC ratio >= 0.7, n = 116]. Clinical
      and demographic parameters were compared between the two groups. RESULTS:
      Multivariate analysis showed that longer duration of disease, greater amount of
      cigarette smoking and absence of rhinosinusitis were significantly related to the
      development of FAO in severe asthmatics. Other parameters, including atopic
      status, pattern of airway inflammatory cells in induced sputum, and frequency of
      asthma exacerbations did not differ between the FAO and RAO groups. CONCLUSION:
      Severe asthma patients with longer disease duration and the absence of
      rhinosinusitis are more likely to develop FAO. This study also demonstrates the
      importance of quitting smoking in order to prevent irreversible airway
      obstruction. Further investigation is required to determine the mechanism by
      which these factors can modify the disease course in Korean patients with severe
      asthma.

PMID- 21194499
TI  - Venom gland transcriptomes of two elapid snakes (Bungarus multicinctus and Naja
      atra) and evolution of toxin genes.
AB  - BACKGROUND: Kraits (genus Bungarus) and cobras (genus Naja) are two
      representative toxic genera of elapids in the old world. Although they are
      closely related genera and both of their venoms are very toxic, the compositions
      of their venoms are very different. To unveil their detailed venoms and their
      evolutionary patterns, we constructed venom gland cDNA libraries and genomic
      bacterial artificial chromosome (BAC) libraries for Bungarus multicinctus and
      Naja atra, respectively. We sequenced about 1500 cDNA clones for each of the
      venom cDNA libraries and screened BAC libraries of the two snakes by blot
      analysis using four kinds of toxin probes; i.e., three-finger toxin (3FTx),
      phospholipase A2 (PLA2), kunitz-type protease inhibitor (Kunitz), and natriuretic
      peptide (NP). RESULTS: In total, 1092 valid expressed sequences tags (ESTs) for
      B. multicinctus and 1166 ESTs for N. atra were generated. About 70% of these ESTs
      can be annotated as snake toxin transcripts. 3FTx (64.5%) and beta bungarotoxin
      (25.1%) comprise the main toxin classes in B. multicinctus, while 3FTx (95.8%) is
      the dominant toxin in N. atra. We also observed several less abundant venom
      families in B. multicinctus and N. atra, such as PLA2, C-type lectins, and
      Kunitz. Peculiarly a cluster of NP precursors with tandem NPs was detected in B.
      multicinctus. A total of 71 positive toxin BAC clones in B. multicinctus and N.
      atra were identified using four kinds of toxin probes (3FTx, PLA2, Kunitz, and
      NP), among which 39 3FTx-positive BACs were sequenced to reveal gene structures
      of 3FTx toxin genes. CONCLUSIONS: Based on the toxin ESTs and 3FTx gene
      sequences, the major components of B. multicinctus venom transcriptome are
      neurotoxins, including long chain alpha neurotoxins (alpha-ntx) and the recently
      originated beta bungarotoxin, whereas the N. atra venom transcriptome mainly
      contains 3FTxs with cytotoxicity and neurotoxicity (short chain alpha-ntx). The
      data also revealed that tandem duplications contributed the most to the expansion
      of toxin multigene families. Analysis of nonsynonymous to synonymous nucleotide
      substitution rate ratios (dN/dS) indicates that not only multigene toxin families
      but also other less abundant toxins might have been under rapid diversifying
      evolution.

PMID- 21194500
TI  - Conditional expression of retrovirally delivered anti-MYCN shRNA as an in vitro
      model system to study neuronal differentiation in MYCN-amplified neuroblastoma.
AB  - BACKGROUND: Neuroblastoma is a childhood cancer derived from immature cells of
      the sympathetic nervous system. The disease is clinically heterogeneous, ranging
      from neuronal differentiated benign ganglioneuromas to aggressive metastatic
      tumours with poor prognosis. Amplification of the MYCN oncogene is a well
      established poor prognostic factor found in up to 40% of high risk
      neuroblastomas.Using neuroblastoma cell lines to study neuronal differentiation
      in vitro is now well established. Several protocols, including exposure to
      various agents and growth factors, will differentiate neuroblastoma cell lines
      into neuron-like cells. These cells are characterized by a neuronal morphology
      with long extensively branched neurites and expression of several neurospecific
      markers. RESULTS: In this study we use retrovirally delivered inducible short
      hairpin RNA (shRNA) modules to knock down MYCN expression in MYCN-amplified (MNA)
      neuroblastoma cell lines. By addition of the inducer doxycycline, we show that
      the Kelly and SK-N-BE(2) neuroblastoma cell lines efficiently differentiate into
      neuron-like cells with an extensive network of neurites. These cells are further
      characterized by increased expression of the neuronal differentiation markers NFL
      and GAP43. In addition, we show that induced expression of retrovirally delivered
      anti-MYCN shRNA inhibits cell proliferation by increasing the fraction of MNA
      neuroblastoma cells in the G1 phase of the cell cycle and that the clonogenic
      growth potential of these cells was also dramatically reduced. CONCLUSION: We
      have developed an efficient MYCN-knockdown in vitro model system to study
      neuronal differentiation in MNA neuroblastomas.

PMID- 21194501
TI  - [Trends in labor medicine in Mexico].
AB  - Labor medicine is the natural field for searching the relation between society,
      work and disease. It is also the field for preventing labor diseases, and for the
      application resulting from search as protection measures in the laboral services.
      At present, tendencies in laboral medicine services are multidisciplinary where
      the specialists need to development competences in epidemiology, clinics,
      investigation, toxicology, dermatology and many other fields.

PMID- 21194502
TI  - [International trends in laboral risk legislation].
AB  - It had been established that labor damage are: laboral injuries, professional
      diseases and others diseases related with laboral conditions. All of them are
      referred to as diseases or damages suffered as a consequence of a laboral
      relations. It is implicated that the damage occurs in the place or during a
      laboral scheduled time with a causal direct relation. There is a trend in the
      Spanish laboral legislation, which is controversial in laboral medicine, because
      it includes a Law for the Prevention of Laboral Risks that consider also to the
      chronic diseases as a cause no traumatic of a laboral risk to conditioned a
      damage during the laboral journey.

PMID- 21194503
TI  - [The influence of preventive programs on laboral injuries].
AB  - OBJECTIVE: To evaluate the impact of preventive programs at enterprises
      affiliated to the Instituto Mexicano del Seguro Social (IMSS) during 2004.
      METHODS: Transversal study in 987 enterprises. VARIABLES: labor injuries (LI) of
      temporal disability, permanent disability and death. ANALYSIS: simple and
      relative frequencies, rates and Anova application to differences. RESULTS: 64.4%
      of the enterprises decrease LI (p < 0.04), with a decrement of 2602 LI (16%); the
      rate of LI per 100 workers declined from 4.19 to 3.60 (p < 0.08), with a decrease
      of 43,369 disability days (10.93%), which represents $8,456,955 MXP. States with
      larger decreases were: Queretaro (80%) p < 0.05; Sinaloa (63%) p < 0.05, and
      Morelos (61%) p < 0.05. Permanent incapacities diminished at 12.1%, p < 0.09; the
      rate of permanent disability per 1000 workers diminished from 1.37 to 1.32 and
      death cases increased from 42 to 49. CONCLUSIONS: the expenses on consultancy by
      IMSS was estimated as $9,341,955 MXP. The savings on temporal and permanent
      incapacities was $33,691,255 MXP with a cost containment of $19,701,310 MXP.
      Preventive programs are profitable, because they generate benefits to the
      workers, the IMSS and the enterprises.

PMID- 21194504
TI  - Pleural mesothelioma in paraoccupational, environmental and occupational patients
      exposed to asbestos.
AB  - OBJECTIVE: To identify the characteristics of pleural mesothelioma in patients
      exposed to asbestos. METHODS: A transverse study in 3700 cases of lung cancer was
      conducted. There were identified 21 cases with mesothelioma. Age, gender, smoking
      history, cancer development, dissemination, cytohistochemistry, lethality and
      total lung capacity were studied. ANOVA test was used. RESULTS: The incidence was
      of 0.45/100,000 patients. Four (19%) corresponded to occupational exposure (OE),
      seven (33%) para-occupational (PE) and ten (48%) environmental (EE). The mean age
      at detection was 50 years for PE, 55 years for EE and 64 years for OE. Twenty
      cases were male. Thirteen patients (62%) were active cigarette smokers. The
      latency time in PE mesothelioma was 34.5 years, in OE 40 years, and in EE more
      than 40 years. In 19 (90%) cases the tumor was disseminated. Diagnosis was
      confirmed by cytohistochemistry. Malignant mesothelioma was reported in 19 (90%)
      cases. The survival period was 5 months for OE patients, 10 in PE and 16 in EE.
      CONCLUSIONS: There is a low incidence of malignant mesothelioma in our
      population. Male was the predominant group. Occupational and paraoccupational
      exposure predominated in patients.

PMID- 21194505
TI  - [Costs in hand amputations derived from labor injuries].
AB  - BACKGROUND: Hand injuries by labor accidents are first rank. It is necessary to
      have a multidisciplinary medical approach to frequently generated temporary and
      permanent disabilities that affect costs to an institution and to enterprise.
      OBJECTIVE: To determine the direct cost (DC) and the indirect cost (IC) of
      complete and partial amputations in hand caused by labor injuries. METHODS: An
      observational study was performed. The data was obtained from labor injuries with
      amputation of a finger or hand that received multidisciplinary management. The
      costs were calculated according to the list of Institutional Unit Costs. The IC
      were obtained with the "safety pays" program. RESULTS: We included 48 cases. The
      average age was 32.17 years; the cost of surgical operations was $767,470; and
      the payment of a partial disability permanent was $1,032,670; the DC of the
      sample of 48 workers was $2,955,007 with an IC of $3,250,507 and a total cost of
      $6,205,515, the average cost per worker of $51,741 for DC, $56,915 for IC and
      $108,657 for the total cost. CONCLUSIONS: Costs of hand injures requires the
      creation of prevention programs.

PMID- 21194506
TI  - [Epidemiologic characteristics of influenza A H1N1 in Queretaro].
AB  - OBJECTIVE: To describe the epidemic profile of Influenza A H1N1 and the main
      actions considered for its control. METHODS: A descriptive and prospective study
      in patients with signs and symptoms suggestive of influenza was performed (fever
      above 38 degrees C, sore throat, cephalgia, muscular and articular pain). Fast
      test and PCR test were done to all suspicious patients. Lethality and mortality
      rates were calculated. RESULTS: From 7678 registered cases, 2220 were confirmed.
      The 75.3% of deaths and 75.4% of patients aged 10 to 59 years. There was no
      difference by sex. The State Health Services reported 45.7% patients and 67.5%
      deaths and the Instituto Mexicano del Seguro Social 41.6% patients and 28.5%
      deaths. The sensitivity of fast test was 79% and there was a 21% of false
      negatives. Clinical features was: fever 98%, migraine 86.5%, dry cough 84.8% and
      general malaise 84.3%. The control strategy included: medical units for immediate
      answer, institutional detection of cases, opportune and accessibility treatment,
      specific areas in urgencies, hospitalization and intensive care attention.
      CONCLUSIONS: The control strategy applied was useful.

PMID- 21194507
TI  - [An e-learning educational strategy for skills development on the prevention,
      diagnosis and treatment on influenza A H1N1].
AB  - OBJECTIVE: To determine the clinical competence with influenza A H1N1 after an e
      learning educational strategy based on the influenza A H1N1 clinical practice
      guideline. METHODS: An observational analytical study which included 860 students
      who responded to the assessment instrument (consistency of 0.89) at the beginning
      and end of phases IV to VII of the e-learning mode course about the prevention,
      diagnosis and treatment of influenza A H1N1. Nonparametric statistics were used.
      RESULTS: We included 25% of students admitted to phases IV to VII of the course.
      There was no statistical difference between the groups at the beginning
      evaluation. The 94.76% of the students were in the lower ranks. After the
      educational intervention 54.64% of students were located at intermediate or
      higher values. Critics to previous actions of colleagues and commitment of
      iatrogenic events were indicators that did not show an increase. A raise in the
      initial score was shown in 646 students, 122 declined and 88 remained unchanged.
      CONCLUSIONS: An e-learning strategy seems to develop adequate skills for the
      prevention, diagnosis and treatment of influenza A H1N1.

PMID- 21194508
TI  - CXCL5 en el tracto respiratorio superior de ninos con influenza A.
AB  - BACKGROUND: Neutrophil infiltration is a major feature in the pathogenesis of
      influenza infection. The factors regulating the neutrophil influx are not fully
      understood. The chemokine CXCL5/ENA-78 is a potent neutrophil chemoattractant,
      that has been implicated in several inflammatory diseases. Our objectives was to
      study the release of CXCL5 in children with natural acquired influenza. METHODS:
      CXCL5 concentration was investigated by immunoenzyme assay in nasal aspirates of
      children (n = 18) in whom respiratory symptoms were precipitated predominantly by
      influenza A virus. RESULTS: There were increased CXCL5 levels in nasal aspirates
      when children were symptomatic as compared with samples from the same children
      when they had been asymptomatic for four weeks (medians 1850 pg/mL vs. 30 pg/mL,
      p < 0.005). We purified CXCL5 from these samples, and demonstrated biological
      neutrophil chemotactic activity. CONCLUSIONS: It is the first in vivo data that
      suggest an important role for CXCL5 in neutrophil influx in proven upper
      respiratory influenza infection. We suggest that CXCL5 might provide a target for
      therapeutic intervention in influenza induced respiratory diseases.

PMID- 21194509
TI  - [A H1N1 influenza infection in pregnant patients].
AB  - BACKGROUND: Despite the severity of infection with influenza virus, little has
      been reported about its presence in pregnant women. OBJECTIVE: To communicate our
      experience on influenza virus H1N1 in pregnant women. METHODS: We conducted a
      retrospective cohort study on 16 hospitalized patients with diagnosis of
      pregnancy and probable or confirmed case of infection with H1N1 influenza virus.
      SUSPECTED CASE: Sudden onset of respiratory infectious process, in 2009, in
      Mexico City. All cases underwent the fast detection test and subsequently
      confirmation by PCR test. Discharge criteria: clinical improvement, PaO(2) above
      60 mm Hg and absence of bilateral consolidation on chest radiographs. Severity
      criteria: type I respiratory failure (PaO(2) < 50 mm Hg) who required mechanical
      ventilatory support, radiographic pattern compatible with multisegmental
      pneumonia and PaO(2)/FiO(2) < 200 mm Hg. RESULTS: The pregnant patient mortality
      was 4.25%. The average age was 25.8 years, with 24.13 weeks of gestation with 5.6
      days average of hospital stay. The main co-morbidity was obesity. CONCLUSIONS:
      The fatal cases were those with longer time of evolution and late diagnosis.

PMID- 21194510
TI  - [The National School of Medicine at the centenary times].
AB  - It analyzes the National School of Medicine situation in the period of 1910 to
      1916, when two historical events rebound in their working; firstly the opening of
      National University of Mexico, and, in the other hand, the beginning of Mexican
      Revolution. Despite of the uneven political, economical, and academic situation,
      the Medicine School kept its interest in the development of excellent medical
      doctors, reviewing subject of study and improving its buildings.

PMID- 21194511
TI  - [Statement Position Paper about photo-protection ot the Mexican Dermatology and
      Oncology Surgery Society].
AB  - Sunlight includes infrared light photons, visible light and ultraviolet light
      (UVL) photons. UVL is the main cause of skin cancer and photo-aging. It is
      absorbed by chromophores in the skin, such as melanin, DNA, RNA, proteins, lipids
      and aromatic amino acids. The absorption of UVL results in photochemical
      reactions involving reactive oxygen species (ROS) with consequent damages to the
      skin. UVL, through different photochemical modifications forming cyclobutane
      dimmers, produce mutations to cell phenomenon called neoplasic transformation.
      The protection of the skin against sunlight is the main action to prevent skin
      cancer and photo-aging. Photo-protection is an effective method for preventing
      skin damage and its consequences. The objective of this consensus was to discuss
      and propose a Statement Position Paper on photo-protection and useful measures
      for their application by the dermatologist and general practitioner in the
      Mexican population.

PMID- 21194512
TI  - [Misuse of terms and phrases in medicine].

PMID- 21194513
TI  - [Clinical study of patients with cranial trauma].
AB  - OBJECTIVE: To identify clinical characteristics and prognosis in patients with
      cranial trauma. METHODS: A longitudinal design was used to study 302 patients
      between the years 2003 and 2006. Variables were mechanism and type of lesion,
      localization, clinical condition, Glasgow Coma Scale and prognosis. Descriptive
      statistics, correlation analysis and odds ratio were applied. RESULTS: Motor
      vehicle accidents were in the first place (47%). The Glasgow mean score was 13.
      Half of the patients presented with loss of consciousness and the most common
      symptom, in 34% of them, was cephalgia. There was a proportionately inverse
      correlation (r-53, < 0.00001) between the Glasgow score and the number of
      hospitalization days. A two percent mortality was equally distributed in the
      period studied. Odds ratio for the motorcycle as mechanism was 2.02 (95% CI, 0.8-
      4.2) and the OR for the frontoparietal region was 2.6 (95% CI, 0.6-2.3).
      CONCLUSIONS: The variables associated with unfavourable prognosis in cranial
      trauma were motorcycle accidents and damage to the frontoparietal region of the
      brain.

PMID- 21194514
TI  - [Laboral talc pneumoconiosis as a low frequency disease].
AB  - OBJECTIVE: To identify the association between exposition to talcum powder and
      talcosilicosis in a cosmetic factory. METHODS: A descriptive and prospective
      survey including 24 workers from the bottling and grinding areas was performed.
      All patients had chest roentgenography. They were separated into two groups: the
      first patients exposed up to a period of five years and the second with more than
      five years exposure. Environmental monitoring of high flow polyvinyl chloride
      filters and galvimetric analysis was performed. The dust analysis was performed
      in 12 inhaling powders, eight environmental and four in workers. A Fisher exact
      test was applied. RESULTS: All of the exposed workers displayed radiographic
      findings compatible with talcosis; 18 (75%) patients had light talcosis and 6
      (25%) moderate. The Fisher test was 13.7 with a p value of 0.004. Dust analysis
      showed: five were reported over the maximum allowed levels corresponding to the
      areas of compact cosmetics grinders, powder grinders, powder dispensers and the
      talcum final line. The analyzed talcum powder contained more than 95% of free
      silica. CONCLUSIONS: The association was confirmed between the exposure and the
      presence of talcosis.

PMID- 21194515
TI  - [Psychoprophylaxis and the rate of cesarean section].
AB  - BACKGROUND: The psychoprophylactic programs (PPP) have been widely used in women
      to face the fear-tension-pain cycle, reducing anxiety and pain during labour. The
      aim was to demonstrate if a PPP reduces the caesarean rate. METHODS: 300 low risk
      pregnant women were included; 100 in the PPP group and 200 in the control group.
      The PPP participants attended theory and practical sessions; they visited labor,
      delivery, recovery and hospitalization areas. Chi-square, Student's t test and
      odds ratio were applied. RESULTS: Pregnancy ended by caesarean section in 35/100
      of PPP group and in 99/200 (49.5%) in control group (p < 0.02, OR = 1.8, IC = 1.1
      2.9). Maternal complications occurred in 13/100 in the PPP group, and 42/200
      (21%) in control group (p = 0.09, RM = 0.56). The newborn (NB) complications were
      observed in 9/100 in PPP and 46/200 (23%) in control group (p < 0.02, OR = 0.33).
      In the PPP group, 70% assisted to three or more sessions. Hospital stance in
      control group, accumulated 17 days more in mothers and 171 days more in NB than
      in the PPP group. CONCLUSIONS: In PPP group observed a caesarean rate reduction
      with fewer maternal and perinatal complications.

PMID- 21194516
TI  - [Two different techniques for volume blood reduction obtained from umbilical
      cord].
AB  - BACKGROUND: To preserve the umbilical cord blood (UCB), the volume containing the
      cells must be reduced before freezing, but the quality, quantity and
      functionality of the cells has to be preserved during this procedure. The aim is
      to compare the performance of two different techniques for volume reduction.
      METHODS: A semiautomatic system and an automatic system were compared as two
      different UCB volume reduction techniques. Total nucleated cell (TNC) counts and
      viability were measured before and after volume reduction. The CD34+ cell counts
      also were measured. RESULTS: Seventy units of cord blood cells (UCB) were
      collected. Thirty-three volume reduction procedures were performed by
      semiautomatic system and thirty-seven by automatic system. The volume recovered
      and the CD34+ count in both techniques was similar, although the viability
      differed slightly (1% higher by Optipress II). CONCLUSIONS: The semiautomatic and
      automatic techniques are suitable to reduce volumes of UCB units.

PMID- 21194517
TI  - [Tuberculosis and coccidiodomycosis in two patients without immune acquired
      deficiency].
AB  - Coccidioidomycosis results from inhaling the spores (arthroconidia) of
      Coccidioides species (Coccidioides immitis or Coccidioides posadasii).
      Tuberculosis is caused by the Mycobacterium tuberculosis complex, classified as
      acid-fast bacilli. It is most commonly transmitted from a patient with infectious
      pulmonary tuberculosis to other persons by droplet nuclei, which are aerosolized
      by coughing, sneezing, or speaking. Northern Mexico is an endemic zone for
      coccidioidomycosis and tuberculosis, both diseases usually appear in an isolated
      way. However, in cases of immunosuppressant in endemic zones, both pathologies
      tend to coexist. In all of the cases, determining the correct diagnosis is very
      difficult because they share epidemiological, clinical, radiographic, and even
      histopathological characteristics. In this paper we present two cases of
      tuberculosis and coccidioidomycosis coexistence. One case presented pulmonary
      disease from both entities, while the other was a relapsing of disseminated
      coccidioidomycosis associated with systemic tuberculosis. The presence of similar
      cases should alert the clinician to consider an early diagnosis of both entities
      in every patient with compatible clinical features. The most important concept is
      to remember that the diagnosis of one of them doesn't exclude the possible
      existence of the other.

PMID- 21194518
TI  - [Thin layer chromatography and infrared spectroscopy in the diagnosis of
      salicylic intoxication].
AB  - Drugs are the main causal agents in intoxications with suicidal purpose.
      Salicylates are few frequently related. In this paper we reported a patient with
      suspicion of acute exogenous intoxication with salicylates. The patient showed
      clinical symptoms of fever, hypoglycemia, low cardiac rhythm, hyperventilation,
      pulmonary edema and coma. We employed analytical toxicology to elucidate the drug
      involved in the intoxication, using thin layer chromatography (TLC) and infrared
      spectrometry to detect acetyl salicylic acid, as the cause agent of intoxication
      clinical pattern, in acids extracts from urine and gastric content. The
      analytical results corresponds with clinical symptoms showed by the patient and
      the information obtained by medical monitoring of him.

PMID- 21194519
TI  - [No traumatic labor accident risk in diabetic patient. View from the Spanish
      legislation].
AB  - The Spanish legislation includes the concept of industrial accidents and
      industrial damage since 1900, although since then in our country some legislative
      changes have been made, reaching the current Occupational Risk Prevention Law
      (ORPL) of 1995 and the legislation emanating from it. This is a controversial
      concept, if we talk about nontraumatic labor injury that carries consequences in
      the workplace, civil, criminal and contentious administrative disputes, and
      economic gains. It differs from others in both in qualifying risk and their
      benefits; the concept also exists in the other European Union countries and in
      different Spanish-American countries. Therefore the objective of the paper is to
      discuss the concept of traumatic industrial accident and non-traumatic labor
      injury in Spain from the point of view of our law and to establish future
      benchmarks with professionals of other countries around us for enabling
      collaboration and joint improvement of the safety and about the health of
      workers.

PMID- 21194520
TI  - Mitochondrial proteases and cancer.
AB  - Mitochondria are a major source of intracellular reactive oxygen species, the
      production of which increases with cancer. The deleterious effects of reactive
      oxygen species may be responsible for the impairment of mitochondrial function
      observed during various pathophysiological states associated with oxidative
      stress and cancer. These organelles are also targets of oxidative damage
      (oxidation of mitochondrial DNA, lipids, protein). An important factor for
      protein maintenance in the presence of oxidative stress is enzymatic reversal of
      oxidative modifications and/or protein degradation. Failure of these processes is
      likely a critical component of the cancer process. Mitochondrial proteases
      degrade misfolded and non-assemble polypeptides, thus performing quality control
      surveillance in the organelle. Mitochondrial proteases may be directly involved
      in cancer development as recently shown for HtrA2/Omi or may regulate crucial
      mitochondrial molecule such as cytochrome c oxidase 4 a subunit of the cytochrome
      c oxidase complex degraded by the Lon protease. Thus, the role of mitochondrial
      proteases is further addressed in the context of oxidative stress and cancer.

PMID- 21194521
TI  - Endocannabinoids and diacylglycerol kinase activity.
AB  - Mammalian diacylglycerol kinases are a family of enzymes that catalyze the
      phosphorylation of diacylglycerol to produce phosphatidic acid. The extent of
      interaction of these enzymes with monoacylglycerols is the focus of the present
      study. Because of the structural relationship between mono- and diacylglycerols,
      one might expect the monoacylglycerols to be either substrates or inhibitors of
      diacylglycerol kinases. This would have some consequence to lipid metabolism. One
      of the lipid metabolites that would be affected is 2-arachidonoyl glycerol, which
      is an endogenous ligand for the CB1 cannabinoid receptor. We determined if the
      monoglycerides 2-arachidonoyl glycerol or 2-oleoyl glycerol affected
      diacylglycerol kinase activity. We found that 2-arachidonoyl glycerol is a very
      poor substrate for either the epsilon or the zeta isoforms of diacylglycerol
      kinases. Moreover, 2-arachidonoyl glycerol is an inhibitor for both of these
      diacylglycerol kinase isoforms. 2-oleoyl glycerol is also a poor substrate for
      these two isoforms of diacylglycerol kinases. As an inhibitor, 2-oleoyl glycerol
      inhibits diacylglycerol kinase epsilon less than does 2-arachidonoyl glycerol,
      while for diacylglycerol kinase zeta, these two monoglycerides have similar
      inhibitory potency. These results have implications for the known role of
      diacylglycerol kinase epsilon in neuronal function and in epilepsy since the
      action of this enzyme will remove 1-stearoyl-2-arachidonoylglycerol, the
      precursor of the endocannabinoid 2-arachidonoyl glycerol.

PMID- 21194522
TI  - N-cholesteryl sphingomyelin-A synthetic sphingolipid with unique membrane
      properties.
AB  - A sphingomyelin chimera in which the amide-linked acyl chain was replaced with
      cholesterol carbamate was prepared and its properties examined. The
      sphingomyelin/cholesterol chimera (N-cholesterol-D-erythro-sphingomyelin) was
      able to form unilamellar vesicles of defined size when extruded through 200nm
      pore size membranes. These N-cholesteryl sphingomyelin bilayers were resistant to
      solubilization by Triton X-100. When N-cholesteryl sphingomyelin was added to N
      palmitoyl sphingomyelin (N-palmitoyl-d-erythro-sphingomyelin) bilayers, it
      increased acyl chain order as determined by 1,6-diphenyl-1,3,5-hexatriene
      fluorescence anisotropy. N-cholesteryl sphingomyelin was, however, not as good an
      inducer of membrane order compared to cholesterol on a molar basis. Differential
      scanning calorimetry studies further showed that the miscibility of N-cholesteryl
      sphingomyelin with N-palmitoyl-d-erythro-sphingomyelin bilayers was non-ideal,
      and the effect of N-cholesteryl sphingomyelin on the N-palmitoyl-d-erythro
      sphingomyelin gel-fluid transition enthalpy differed from that seen with
      cholesterol. Together with N-palmitoyl-d-erythro-sphingomyelin, the N-cholesteryl
      sphingomyelin chimera was able to form sterol-enriched ordered domains in a fluid
      1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer. N-cholesteryl
      sphingomyelin in the absence of N-palmitoyl-d-erythro-sphingomyelin was unable to
      form such sterol-enriched ordered domains in a 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine bilayer. However, N-cholesteryl sphingomyelin markedly increased
      the affinity of cholestatrienol for N-cholesteryl sphingomyelin containing 1
      palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayers, suggesting that N
      cholesteryl sphingomyelin was able to somehow stabilize sterol interaction in
      fluid bilayers. Based on our results, we conclude that N-cholesteryl
      sphingomyelin behaved more like a cholesterol than a sphingolipid in fluid
      bilayer membranes. Because N-cholesteryl sphingomyelin increased bilayer order,
      conferred resistance against detergent solubilization, and is not degradable by
      phospholipases A(2), it could constitute a good lipocomplex matrix for drug
      delivery vehicles.

PMID- 21194523
TI  - Helium preconditioning attenuates hypoxia/ischemia-induced injury in the
      developing brain.
AB  - Recent studies show helium may be one kind of neuroprotective gas. This study
      aimed to examine the short and long-term neuroprotective effects of helium
      preconditioning in an established neonatal cerebral hypoxia-ischemia (HI) model.
      Seven-day-old rat pups were subjected to left common carotid artery ligation and
      then 90 min of hypoxia (8% oxygen at 37 degrees C). The preconditioning group
      inhaled 70% helium-30% oxygen for 5 min three times with an interval of 5 min 24h
      before HI insult. Pups were decapitated 24h after HI and brain morphological
      injury was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining, Nissl
      and TUNEL staining. Caspase-3 activity in the brain was measured. Five weeks
      after HI, postural reflex testing and Morris water maze testing were conducted.
      Our results showed that helium preconditioning reduced the infarct ratio,
      increased the number of survival neurons, and inhibited apoptosis at the early
      stage of HI insult. Furthermore, the sensorimotor function and the cognitive
      function were improved significantly in rats with helium preconditioning. The
      results indicate that helium preconditioning attenuates HI induced brain injury.

PMID- 21194524
TI  - Neonatal sensory deprivation promotes development of absence seizures in adult
      rats with genetic predisposition to epilepsy.
AB  - Absence epilepsy has age-related onset. In a WAG/Rij rat genetic model, absence
      seizures appear after puberty and they are increased with age. It is known that
      (1) epileptic activity in WAG/Rij rats is initiated at the perioral area in the
      somatosensory cortex; (2) sensory deprivation, i.e., whisker trimming during the
      critical period of development, could enhance excitatory activity in the
      somatosensory cortex. It is hypothesized that the cortex may become more
      excitable after neonatal vibrissae removal, and this may precipitate absence
      seizures in adult rats. We found that whisker trimming during the first postnatal
      weeks caused more rapid development of EEG seizure activity in adult WAG/Rij
      rats. Epileptic discharges in the trimmed rats were more numerous (vs control),
      showed longer duration and often appeared in desynchronized and drowsy EEG. The
      number of absence-like spindle-shaped EEG events (spike-wave spindles) in the
      whisker-trimmed rats was higher than in control, especially during the
      intermediate sleep state. An age-dependent increase of intermediate sleep state
      was found in the trimmed rats, but not in the intact animals. We discuss
      epigenetic factors that can modulate absence epilepsy in genetically prone
      subjects.

PMID- 21194525
TI  - Phosphodiesterase10A: abundance and circadian regulation in the retina and
      photoreceptor of the rat.
AB  - Phosphodiesterase10A (PDE10A) is a dual specific cyclic nucleotide
      phosphodiesterase that is specifically enriched in striatum and which has gained
      attention as a therapeutic target for psychiatric disorders. The present study
      shows that PDE10A is also highly expressed in retinal neurons including
      photoreceptors. The levels of PDE10A transcript and protein display daily rhythms
      which could be seen in preparations of the whole retina. Corresponding changes in
      PDE10A mRNA were seen in photoreceptors isolated using laser microdissection.
      This suggests that the expressional control of the photoreceptor Pde10a gene
      contributes to the observed cyclicity in the amount of retinal PDE10A. The daily
      rhythmicity in the retinal PDE10A mRNA amount is retained under constant darkness
      but can be blocked by constant light or modulated by the lighting regime. It
      therefore appears to be driven by the endogenous retinal clock system which
      itself is entrained by light. The findings presented place PDE10A in the context
      of the visual system and suggest a role of PDE10A in the adaptation of cyclic
      nucleotide signaling to daily changes in light intensity in retinal neurons
      including photoreceptors.

PMID- 21194526
TI  - A study of ACE and ADD1 polymorphism in ischemic and hemorrhagic stroke.
AB  - BACKGROUND: Stroke is a common cerebrovascular accident. ACE and ADD1 gene are
      known to be associated with vascular complications leading to stroke
      susceptibility. The present study was carried out to evaluate the relative
      frequency of ACE and ADD1 common polymorphisms in ischemic stroke and
      intracerebral hemorrhage (ICH). METHODS: A total of 386 CT or MRI proven stroke
      patients were included; 193 each had ischemic stroke and ICH. The locations and
      type of stroke were noted. ACE- I/D (rs4646994) and ADD1 (rs4961) gene
      polymorphisms were analyzed by polymerase chain reaction (PCR). The genotype and
      allele frequencies of ACE and ADD1 polymorphisms were compared between patients
      and controls as well as between ischemic stroke and ICH. RESULTS: ACE (DD)
      genotype was significantly higher in ischemic stroke (37.8%) and ICH (33.7%)
      compared to controls (11.7%). D allele was also more frequent in ischemic stroke
      (57.3%) and ICH (56.7%) compared to controls (38.3%). ADD1 (WW) genotype and W
      allele frequencies were not significantly different in ischemic stroke, ICH and
      controls. In contrast, we found a synergistic role of ACE (DD)*ADD1(GW)
      interaction showing a positive association in both ischemic and hemorrhagic
      strokes. CONCLUSION: Our study suggests that ACE (DD) genotype and D allele
      significantly increase the susceptibility to ischemic and hemorrhagic strokes.

PMID- 21194527
TI  - Transdifferentiation of tadpole pancreatic acinar cells to duct cells mediated by
      Notch and stromelysin-3.
AB  - The tadpole pancreas has differentiated acinar cells but an underdeveloped ductal
      system. At the climax of metamorphosis thyroid hormone (TH) induces the tadpole
      acinar cells to dedifferentiate to a progenitor state. After metamorphosis is
      complete the exocrine pancreas redifferentiates in the growing frog forming a
      typical vertebrate pancreas including a complex ductal system. A micro array
      analysis found that TH up regulates stromelysin 3 (ST3, matrix metalloproteinase
      11) in the exocrine pancreas at metamorphic climax. Transgenic tadpoles were
      prepared with an elastase promoter driving either the ST3 gene or the
      constitutively active form of Notch (IC). Expression of the transgenes was
      controlled by the tetracycline system. A few days after either of these
      transgenes is activated by doxycycline the pancreatic acinar cells turn into duct
      like cells. This transdetermination occurs without cell division since both
      acinar and ductal markers can be visualized transiently in the same cell. We
      propose that remodeling of the tadpole acinar cells is initiated when ST3 is up
      regulated by TH. Stromelysin-3 then cleaves and activates Notch.

PMID- 21194528
TI  - Ghrelin protects H9c2 cells from hydrogen peroxide-induced apoptosis through NF
      kappaB and mitochondria-mediated signaling.
AB  - Oxidative stress is a major mechanism underlying the pathogenesis of
      cardiovascular disease. Herein we investigate the protective effects of ghrelin
      in H(2)O(2)-induced apoptosis of H9c2 cells, as well as the possible molecular
      mechanisms involved. To study apoptosis, the cells were assessed by morphologic
      examination, MTS assay, Annexin V-propidium iodide dual staining and TUNEL
      analysis. Intracellular reactive oxygen species (ROS) production and
      mitochondrial membrane potential were also measured. To investigate the
      underlying molecular mechanisms, the expression of Bcl-2, Bax, active caspase-9
      and NF-kappaB were assessed by Western blotting, and caspase-3 activity was
      determined by a colorimetric activity assay kit. After stimulation with H(2)O(2)
      for 18h, H9c2 cells viability decreased significantly; a large fraction of cells
      underwent apoptosis. We observed a dose-dependent rescue of H9c2 cells from
      H(2)O(2)-induced apoptosis in the presence of different ghrelin concentrations.
      Preincubation with ghrelin also restored the ROS and mitochondrial membrane
      potential levels that had been altered by H(2)O(2) treatment. Moreover, ghrelin
      decreased H(2)O(2)-induced Bax production and caspase-9 activation, and increased
      Bcl-2 levels. NF-kappaB phosphorylation was also significantly inhibited by
      ghrelin in H(2)O(2)-treated cells. Caspase-3 activation was suppressed by ghrelin
      in H(2)O(2)-treated H9c2 cells in a dose-dependent manner. In summary, ghrelin
      protects H9c2 cells from oxidative stress-induced apoptosis through
      downregulation of Bax expression, caspase-9 activation and NF-kappaB
      phosphorylation, and upregulation of Bcl-2 expression. Caspase-3 activation was
      also reduced in a dose-dependent manner. These data suggest that ghrelin might
      protect against cardiovascular disease by protecting the mitochondria.

PMID- 21194529
TI  - Association between -786TC polymorphism in the endothelial nitric oxide synthase
      gene and hypertension in the Tunisian population.
AB  - BACKGROUND: Nitric oxide (NO) is produced by endothelial cells and serves as a
      potent vasodilator. Several lines of evidence have shown that NO plays an
      important role in the regulation of blood pressure and regional blood flow.
      Recent genetic studies have shown an association between the -786TC polymorphism
      in the endothelial nitric oxide synthase gene (NOS3) and coronary artery
      diseases, but any possible association with hypertension has been controversial.
      In the present study, we examined a possible association between the -786TC
      polymorphism of the NOS3 gene and hypertension in a sample of the Tunisian
      population. METHODS: A total of 288 unrelated Tunisian patients with hypertension
      and 373 normotensive subjects were included in the study. The -786TC gene
      polymorphism was analyzed by PCR-RFLP. RESULTS: A significant difference in
      genotype distribution and allele frequency was observed between patients and
      controls. Patients with hypertension had a frequency of 19.7% for CC genotype,
      52.9% for TC genotype and 27.3% for TT genotype. The control had a frequency of
      14.7% for the CC genotype, 47.2% for the TC genotype and 38.1% for the TT
      genotype (chi2=9.09, p=0.01). The hypertension patient group showed a significant
      higher frequency of the C allele compared to the controls (0.46 vs. 0.38;
      chi2=8.26, p=0.004). The odds ratio of hypertension for C vs. T allele
      frequencies was statistically significant 1.59 (1.14-2.21) at 95% CI, p = 0.004
      in men, whereas it was non-significant in women 1.21 (0.87-1.67), p=0.23.
      CONCLUSION: The present study showed a significant and independent association
      between the -786TC gene polymorphism (presence of C allele) and hypertension in
      the Tunisian population.

PMID- 21194530
TI  - Absence of galectin-3 does not affect the development of experimental tongue
      carcinomas in mice.
AB  - BACKGROUND: Galectin-3 is a lectin that presents pivotal roles in tumor biology
      and there are no studies evaluating their expression in dysplasias and carcinomas
      developed from tongue carcinogenesis models. AIMS: To investigate the role of
      galectin-3 in the development of tongue carcinomas using a mouse model of oral
      carcinogenesis. METHODS: Galectin-3-deficient (gal3(-/-)) and wild-type
      (gal3(+/+)) mice were challenged with 4-nitroquinoline-1-oxide in drinking water
      for 16weeks and killed at different times. Tongues were removed and the number of
      dysplasias and carcinomas was counted. An immunohistochemical study for galectin
      3 was performed only in the tongue from gal3(+/+) mice. RESULTS: In both groups,
      a reduction of dysplasias and an increase of carcinomas from week 16 to week 32
      (p>0.05) were observed. A predominance of high cytoplasmic and nuclear galectin-3
      expression was observed in carcinomas (64.7%) and dysplasias (55.5%),
      respectively (p>0.05). The perilesional areas always presented a statistical
      cytoplasmic and nuclear galectin-3 overexpression. CONCLUSIONS: Absence of
      galectin-3 did not directly affect the process of carcinogenesis and a cytoplasm
      shift of galectin-3 seems to be associated with development of tongue carcinomas.

PMID- 21194531
TI  - Focus on molecules: protein kinase CK2.

PMID- 21194532
TI  - Flow cytometry-based assay to evaluate human serum MUC1-Tn antibodies.
AB  - Mucin-1 (MUC1) is a heavily O-glycosylated, transmembrane protein that is
      expressed on the apical surface of most secretory epithelia. In malignantly
      transformed epithelia, MUC1 has lost its apical distribution, is
      underglycosylated and is secreted into the circulation. Due to the
      underglycosylation of MUC1, cancer-specific MUC1-Tn/STn antigens, which are
      highly immunogenic, become exposed. We aimed at developing a system that allows
      detection of antibodies directed to the native form of MUC1 and the
      underglycosylated MUC1-Tn epitopes. To this end, we made use of the Chinese
      Hamster Ovary (CHO) ldlD cell line stably transfected with MUC1. This cell line
      has a glycosylation defect, which can be reversed by addition of different
      monosaccharides to the cell culture and enables the production of cells
      expressing the MUC1-Tn glycoforms. After validation with glycospecific
      antibodies, the CHO-ldlD MUC1 system was used to detect serum MUC1 and MUC1-Tn
      antibodies. Using this system, we could confirm the presence of MUC1-Tn
      antibodies in the serum of a patient vaccinated with a truncated MUC1 peptide.
      This indicates that the CHO-ldlD MUC1 system represents a flow cytometry-based
      technique to detect antibodies binding to the underglycosylated MUC1 protein.
      This cellular system is complementary to the previously published methods to
      detect MUC1 serum antibodies, since the antibodies to the native protein are
      evaluated and therefore it can be effectively used for MUC1 antibody monitoring
      in vaccination studies as well as for functional assays.

PMID- 21194533
TI  - The evolution of conditional dispersal and reproductive isolation along
      environmental gradients.
AB  - Dispersal modulates gene flow throughout a population's spatial range. Gene flow
      affects adaptation at local spatial scales, and consequently impacts the
      evolution of reproductive isolation. A recent theoretical investigation has
      demonstrated that local adaptation along an environmental gradient, facilitated
      by the evolution of limited dispersal, can lead to parapatric speciation even in
      the absence of assortative mating. This and other studies assumed unconditional
      dispersal, so individuals start dispersing without regard to local environmental
      conditions. However, many species disperse conditionally; their propensity to
      disperse is contingent upon environmental cues, such as the degree of local
      crowding or the availability of suitable mates. Here, we use an individual-based
      model in continuous space to investigate by numerical simulation the relationship
      between the evolution of threshold-based conditional dispersal and parapatric
      speciation driven by frequency-dependent competition along environmental
      gradients. We find that, as with unconditional dispersal, parapatric speciation
      occurs under a broad range of conditions when reproduction is asexual, and under
      a more restricted range of conditions when reproduction is sexual. In both the
      asexual and sexual cases, the evolution of conditional dispersal is strongly
      influenced by the slope of the environmental gradient: shallow environmental
      gradients result in low dispersal thresholds and high dispersal distances, while
      steep environmental gradients result in high dispersal thresholds and low
      dispersal distances. The latter, however, remain higher than under unconditional
      dispersal, thus undermining isolation by distance, and hindering speciation in
      sexual populations. Consequently, the speciation of sexual populations under
      conditional dispersal is triggered by a steeper gradient than under unconditional
      dispersal. Enhancing the disruptiveness of frequency-dependent selection, more
      box-shaped competition kernels dramatically lower the speciation-enabling slope
      of the environmental gradient.

PMID- 21194534
TI  - Transient pulse formation in jasmonate signaling pathway.
AB  - The jasmonate (JA) signaling pathway in plants is activated as defense response
      to a number of stresses like attacks by pests or pathogens and wounding by
      animals. Some recent experiments provide significant new knowledge on the
      molecular detail and connectivity of the pathway. The pathway has two major
      components in the form of feedback loops, one negative and the other positive. We
      construct a minimal mathematical model, incorporating the feedback loops, to
      study the dynamics of the JA signaling pathway. The model exhibits transient gene
      expression activity in the form of JA pulses in agreement with experimental
      observations. The dependence of the pulse amplitude, duration and peak time on
      the key parameters of the model is determined computationally. The deterministic
      and stochastic aspects of the pathway dynamics are investigated using both the
      full mathematical model and a reduced version of it. We also compare the
      mechanism of pulse formation with the known mechanisms of pulse generation in
      some bacterial and viral systems.

PMID- 21194535
TI  - Group size, grooming and fission in primates: a modeling approach based on group
      structure.
AB  - In social animals, fission is a common mode of group proliferation and dispersion
      and may be affected by genetic or other social factors. Sociality implies
      preserving relationships between group members. An increase in group size and/or
      in competition for food within the group can result in decrease certain social
      interactions between members, and the group may split irreversibly as a
      consequence. One individual may try to maintain bonds with a maximum of group
      members in order to keep group cohesion, i.e. proximity and stable relationships.
      However, this strategy needs time and time is often limited. In addition,
      previous studies have shown that whatever the group size, an individual interacts
      only with certain grooming partners. There, we develop a computational model to
      assess how dynamics of group cohesion are related to group size and to the
      structure of grooming relationships. Groups' sizes after simulated fission are
      compared to observed sizes of 40 groups of primates. Results showed that the
      relationship between grooming time and group size is dependent on how each
      individual attributes grooming time to its social partners, i.e. grooming a few
      number of preferred partners or grooming equally or not all partners. The number
      of partners seemed to be more important for the group cohesion than the grooming
      time itself. This structural constraint has important consequences on group
      sociality, as it gives the possibility of competition for grooming partners,
      attraction for high-ranking individuals as found in primates' groups. It could,
      however, also have implications when considering the cognitive capacities of
      primates.

PMID- 21194536
TI  - Evolutionary dynamics of BRCA1 alterations in breast tumorigenesis.
AB  - Cancer results from the accumulation of alterations in oncogenes and tumor
      suppressor genes. Tumor suppressors are classically defined as genes which
      contribute to tumorigenesis if their function is lost. Genetic or epigenetic
      alterations inactivating such genes may arise during somatic cell divisions or
      alternatively may be inherited from a parent. One notable exception to this rule
      is the BRCA1 tumor suppressor that predisposes to hereditary breast cancer when
      lost. Genetic alterations of this gene are hardly ever observed in sporadic
      breast cancer, while individuals harboring a germline mutation readily accumulate
      a second alteration inactivating the remaining allele--a finding which represents
      a conundrum in cancer genetics. In this paper, we present a novel mathematical
      framework of sporadic and hereditary breast tumorigenesis. We study the dynamics
      of genetic alterations driving breast tumorigenesis and explore those scenarios
      which can explain the absence of somatic BRCA1 alterations while replicating all
      other disease statistics. Our results support the existence of a heterozygous
      phenotype of BRCA1 and suggest that the loss of one BRCA1 allele may suppress the
      fitness advantage caused by the inactivation of other tumor suppressor genes.
      This paper contributes to the mathematical investigation of breast tumorigenesis.

PMID- 21194537
TI  - Steroid glycosides from marine organisms.
AB  - Structures, taxonomic distribution and biological activities of steroid
      glycosides isolated from marine organisms over the last 8-10 years are reviewed.
      The bibliography includes 130 references.

PMID- 21194538
TI  - Tannic acid ameliorates doxorubicin-induced cardiotoxicity and potentiates its
      anti-cancer activity: potential role of tannins in cancer chemotherapy.
AB  - Doxorubicin, an anthracycline antibiotic, is widely used in the treatment of
      various solid tumors including breast cancer. However, its use is limited due to
      a variety of toxicities including cardiotoxicity. The present study aimed to
      evaluate the effect of tannic acid, a PARG/PARP inhibitor and an antioxidant, on
      doxorubicin-induced cardiotoxicity in H9c2 embryonic rat heart myoblasts and its
      anti-cancer activity in MDA-MB-231 human breast cancer cells as well as in DMBA
      induced mammary tumor animals. Doxorubicin-induced cardiotoxicity was assessed by
      measurement of heart weight, plasma LDH level and histopathology. Bcl-2, Bax,
      PARP-1 and p53 expression were examined by western blotting. Our results show
      that tannic acid prevents activation of PARP-1, reduces Bax and increases Bcl-2
      expression in H9c2 cells, thus, preventing doxorubicin-induced cell death.
      Further, it reduces the cell viability of MDA-MB-231 breast cancer cells,
      increases p53 expression in mammary tumors and shows maximum tumor volume
      reduction, suggesting that tannic acid potentiates the anti-cancer activity of
      doxorubicin. To the best of our knowledge, this is the first report which shows
      that tannic acid ameliorates doxorubicin-induced cardiotoxicity and potentiates
      its anti-cancer activity both in vitro (H9c2 and MDA-MB-231 cells) as well as in
      in vivo model of DMBA-induced mammary tumor animals.

PMID- 21194539
TI  - A new quantitative PCR assay for the detection of hepatotoxigenic cyanobacteria.
AB  - Toxin-producing cyanobacteria are a worldwide threat to both human and animal
      health. The hepatotoxins microcystin and nodularin are the most commonly
      occurring toxins produced by bloom-forming cyanobacteria. They are cyclic
      peptides that are synthesized nonribosomally by a multienzyme complexes encoded
      within the microcystin (mcyS) and nodularin (ndaS) synthetase gene clusters.
      Early detection of potentially toxic blooms would allow for pre-emptive action to
      reduce consumer exposure to cyanotoxins. We have developed a quantitative PCR
      (qPCR) assay based on SYBR-green chemistry for the detection of potentially
      hepatotoxic cyanobacteria spanning all known microcystin and nodularin producing
      taxa using primers specifically targeting mcyE and ndaF. The qPCR assay was
      validated against previously analyzed cyanobacterial bloom samples. Whole cell
      qPCR using cultured M. aeruginosa PCC7806 and non-toxic M. aeruginosa UTEX2386
      had a sensitivity of 1000 cells ml-1. In summary, we have developed a robust and
      sensitive molecular method for the detection and quantification of
      hepatotoxigenic cyanobacteria in bloom samples. This technology offers several
      advantages over traditional and contemporary testing protocols currently used to
      assess water quality.

PMID- 21194540
TI  - Pre- versus post-column oxidation liquid chromatography fluorescence detection of
      paralytic shellfish toxins.
AB  - Both pre- and post-column oxidation liquid chromatography methods with
      fluorescence detection are available for detecting paralytic shellfish toxins.
      Each method has been evaluated in multiple laboratories and validated as a
      potential alternative to the mouse bioassay. This communication compares the
      advantages and limitations of both methods. For a given laboratory, the selection
      of either method may be based primarily on practicality and less on any
      deficiencies in scientific merit.

PMID- 21194541
TI  - ImKTx88, a novel selective Kv1.3 channel blocker derived from the scorpion
      Isometrus maculates.
AB  - Scorpion toxins are useful in the structure-function research of ion channels and
      valuable resources for drug design. The Kv1.3 channel is an important
      pharmacological target for the therapy of T cell-mediated autoimmune diseases,
      and many toxin peptides targeting Kv1.3 have been identified as good drug
      candidates in recent years. In this study, a novel toxin gene ImKTx88 was
      isolated from the venom of the scorpion Isometrus maculates through the
      construction of the cDNA library method, and the recombinant toxin peptide was
      purified and characterized physiologically. The mature peptide of ImKTx88
      contained 39 amino acid residues including six cysteines and was predicted to be
      a new member of alpha-KTx scorpion family by sequence analysis. The
      electrophysiological experiments further indicated that the rImKTx88 peptide had
      a novel pharmacological profile: it inhibited Kv1.3 channel current with an IC50
      of 91 +/- 42 pM, and exhibited very good selectivity for Kv1.3 over Kv1.1 (4200
      fold) and Kv1.2 (93000-fold) channels, respectively. All these results suggested
      that, as a new selective Kv1.3 channel blocker, the ImKTx88 peptide may serve as
      a potential drug candidate in the therapy of autoimmune diseases.

PMID- 21194542
TI  - The cytolytic and cytotoxic activities of palytoxin.
AB  - Palytoxin (PlTX) is one of the largest compound present in nature and, with its
      strong ability to modify the normal function of different biological systems, is
      also classified as one of the most potent biotoxins. Many alterations are
      triggered by PlTX, directly or indirectly related to its interaction with
      Na(+),K(+)-ATPase and the consequent conversion of this ion pump into a non
      specific cation channel. The resulting perturbation of Na(+), K(+), Ca(2+) and
      H(+) ion fluxes is the driving force of PlTX-induced cytotoxic events,
      culminating with system disruption and, finally, cell death. The modifications in
      the distribution of these ions across the plasma membrane play key roles in the
      promotion of the PlTX-induced cytolytic and cytotoxic responses. In this
      scenario, PlTX-specific cytolysis can be part, but might not necessarily
      represent a unique aspect of the cytotoxic effects of the toxin. Owing to the
      complex array of responses, some of them being cell-type-specific and/or affected
      by experimental conditions, the distinction between cytolytic and cytotoxic
      events becomes ill-defined, but the two responses show distinct features, whose
      further characterization could contribute to a better understanding of the
      molecular mechanism of cellular effects induced by PlTX.

PMID- 21194543
TI  - The development of Byetta (exenatide) from the venom of the Gila monster as an
      anti-diabetic agent.
AB  - The development of Byetta (synthetic exendin-4; exenatide) as a treatment of
      diabetes arose from two, parallel lines of investigation. The development of the
      'incretin concept' which hypothesised that hormones from the gut contributed to
      the insulin secretion in response to meals, led to the identification of glucagon
      like peptide 1 (GLP-1) as an important 'incretin' hormone. GLP-1 not only
      increases insulin secretion but increases beta-cell proliferation and survival,
      suppresses glucagon secretion, delays gastric emptying and suppresses appetite,
      all of these actions contributing to a potential anti-diabetic effect. However,
      GLP-1 has a very short half due to its rapid breakdown by dipeptidyl peptidase IV
      and ectopeptidases. A systematic investigation of the composition and activity of
      venom from the Gila monster, Heloderma suspectum, led to the isolation of a 39
      amino acid peptide, designated exendin-4, showing 53% structural homology with
      GLP-1(7-36). Exendin-4 mimicked GLP-1 through stimulating the GLP-1 receptor. The
      much greater stability of exendin-4 led to its experimental and clinical
      evaluation as an anti-diabetic agent and its introduction to the market in 2005.

PMID- 21194544
TI  - Can 14- to 20-month-old children learn that a tool serves multiple purposes? A
      developmental study on children's action goal prediction.
AB  - We investigated infants' visual anticipations to the target of an ongoing tool
      use action and examined if infants can learn that tools serve multiple functions
      and can thus be used on different targets. Specifically, we addressed the
      question at what age children are able to predict the goal of an ongoing tool-use
      action on the basis of how the actor initiates the action. Fourteen- and 20-month
      old children watched a model using a tool to execute two different actions. Each
      way of grasping and holding the tool was predictive for its use on a particular
      target. Analyses revealed that the 20- but not the 14-month-olds were able to
      visually anticipate to the correct target during action observation, which
      suggests that they perceived the initial part of the tool-use action as
      predictive for its use on an action target.

PMID- 21194545
TI  - Olanzapine and risperidone disrupt conditioned avoidance responding by
      selectively weakening motivational salience of conditioned stimulus: further
      evidence.
AB  - Suppression of conditioned avoidance response is a preclinical behavioral index
      of antipsychotic activity. Previous work shows that olanzapine and risperidone
      disrupt avoidance response elicited by a less salient conditioned stimulus (CS2)
      to a greater extent than avoidance elicited by a more salient stimulus (CS1),
      suggesting that antipsychotic drugs may have a weakening action on motivational
      salience of stimuli. In the present study, we further examined this mechanism of
      antipsychotic action, focusing on the possible impact of baseline difference of
      CS1 and CS2 response rates on the avoidance-disruptive effect of olanzapine and
      risperidone. Rats were first trained to acquire avoidance responding in a
      procedure in which the number of CS2 trials (i.e. 20) was twice the number of CS1
      trials (i.e. 10), but the percentage of CS2-shock pairing was set at 25% lower
      (15 trials out of 20) than the percentage of CS1-shock pairing (20 trials out of
      20). They were then tested daily under olanzapine (0.5 and 1.0 mg/kg, sc) or
      risperidone (0.33 and 1.0 mg/kg, sc) for 5 consecutive days. Repeated olanzapine
      and risperidone treatment dose-dependently disrupted avoidance responding to both
      CS1 and CS2. Both drugs at the high dose disrupted the CS2 avoidance to a greater
      extent than the CS1 avoidance. In the final challenge test, rats previously
      treated with olanzapine were tested under risperidone (0.33 mg/kg), whereas rats
      previously treated with risperidone were tested under olanzapine (0.5 mg/kg).
      Results show that rats previously treated with risperidone 1.0mg/kg group made
      significantly fewer avoidance responses than the vehicles under olanzapine at 0.5
      mg/kg. These findings confirm that olanzapine and risperidone disrupt avoidance
      response primarily by selectively attenuating the motivational salience of the
      CS. The present study also suggests that there is a generality of antipsychotic
      drug experience that is mediated by a shared interoceptive drug state mechanism.

PMID- 21194546
TI  - Semi-automated atlas-based analysis of brain histological sections.
AB  - Quantifying the location and/or number of features in a histological section of
      the brain currently requires one to first, manually register a corresponding
      section from a tissue atlas onto the experimental section and second, count the
      features. No automated method exists for the first process (registering), and
      most automated methods for the second process (feature counting) operate reliably
      only in a high signal-to-noise regime. To reduce experimenter bias and
      inconsistencies and increase the speed of these analyses, we developed Atlas
      Fitter, a semi-automated, open-source MatLab-based software package that assists
      in rapidly registering atlas panels onto histological sections. We also developed
      CellCounter, a novel fully automated cell counting algorithm that is designed to
      operate on images with non-uniform background intensities and low signal-to-noise
      ratios.

PMID- 21194547
TI  - Frequency recognition in an SSVEP-based brain computer interface using empirical
      mode decomposition and refined generalized zero-crossing.
AB  - This paper presents an empirical mode decomposition (EMD) and refined generalized
      zero crossing (rGZC) approach to achieve frequency recognition in steady-stated
      visual evoked potential (SSVEP)-based brain computer interfaces (BCIs). Six light
      emitting diode (LED) flickers with high flickering rates (30, 31, 32, 33, 34, and
      35 Hz) functioned as visual stimulators to induce the subjects' SSVEPs. EEG
      signals recorded in the Oz channel were segmented into data epochs (0.75 s). Each
      epoch was then decomposed into a series of oscillation components, representing
      fine-to-coarse information of the signal, called intrinsic mode functions (IMFs).
      The instantaneous frequencies in each IMF were calculated by refined generalized
      zero-crossing (rGZC). IMFs with mean instantaneous frequencies (f(GZC)) within
      29.5 Hz and 35.5 Hz (i.e., 29.5<=f(GZC)<=35.5 Hz) were designated as SSVEP
      related IMFs. Due to the time-locked and phase-locked characteristics of SSVEP,
      the induced SSVEPs had the same frequency as the gazing visual stimulator. The
      LED flicker that contributed the majority of the frequency content in SSVEP
      related IMFs was chosen as the gaze target. This study tests the proposed system
      in five male subjects (mean age=25.4+/-2.07 y/o). Each subject attempted to
      activate four virtual commands by inputting a sequence of cursor commands on an
      LCD screen. The average information transfer rate (ITR) and accuracy were 36.99
      bits/min and 84.63%. This study demonstrates that EMD is capable of extracting
      SSVEP data in SSVEP-based BCI system.

PMID- 21194548
TI  - Somatostatin receptor-3 mediated intracellular signaling and apoptosis is
      regulated by its cytoplasmic terminal.
AB  - In the present study, we describe the role of cytoplasmic terminal (C-tail)
      domain in regulating coupling to adenylyl cyclase, signaling, and apoptosis in
      human embryonic kidney (HEK-293) cells transfected with wild type (wt)-hSSTR3 and
      C-tail deleted mutants. Cells transfected with wt-hSSTR3 and C-tail mutants show
      comparable membrane expression; however, display decreased expression in presence
      of agonist. wt-hSSTR3 exists as preformed homodimer at cell surface in basal
      conditions and decreases in response to agonist. Cells expressing C-tail mutants
      also show evidence of homodimerization with the same intensity as wt-hSSTR3. The
      agonist-dependent inhibition of cyclic adenosine monophosphate (cAMP) was lost in
      cells expressing C-tail mutants. Agonist treatment in cells expressing wt-hSSTR3
      resulted in inhibition of cell proliferation, increased expression of PARP-1, and
      TUNEL positivity in proliferating cell nuclear antigen (PCNA)-positive cells. The
      agonist mediated increase in membrane expression of protein tyrosine phosphatase
      (PTP) seen with wt-hSSTR3 was diminished in C-tail mutants, which was accompanied
      with the loss of receptor's ability to induce apoptosis. Taken together, our data
      provide new insights into C-tail-dependent regulation of cell signaling and
      apoptosis by hSSTR3.

PMID- 21194549
TI  - Cold pressor stress affects cardiac attenuation of startle.
AB  - Stress may affect cardio-afferent neural traffic. We investigated whether acute
      autonomic stress has an impact on cardiac modulation of startle (CMS), a
      'background' methodology for assessing baro-afferent signal transmission.
      Therefore, 38 healthy volunteers received acoustic startle stimuli (105 dB) at 6
      different latencies relative to the R-wave (R +0, 100, 200, 300, 400, and 500 ms;
      randomized order), both before and immediately after either a cold pressor (n =
      19) or a control intervention (n = 19). Blood pressure was enhance d
      significantly in the cold pressor group right after the intervention (+13.7/5.7
      mmHg), reflecting sustained autonomic activation after the stress procedure.
      Before stress, startle responses were lowest for latencies of R +200 and +300 ms,
      corroborating previous findings. After the cold pressor test, startle
      responsiveness was lowest for earlier latencies (R +0, +100 and +200 ms). Stress
      facilitation of pre-ejection baro-afferent traffic originating from atrial
      mechano-sensitive receptors may be associated with this time shift effect. We
      conclude that the cardiac modulation of startle is sensitive to altered temporal
      baro-afferent feedback characteristics induced by stress and autonomic
      activation.

PMID- 21194550
TI  - The role of oscillatory brain activity in object processing and figure-ground
      segmentation in human vision.
AB  - The perception of an object as a single entity within a visual scene requires
      that its features are bound together and segregated from the background and/or
      other objects. Here, we used magnetoencephalography (MEG) to assess the
      hypothesis that coherent percepts may arise from the synchronized high frequency
      (gamma) activity between neurons that code features of the same object. We also
      assessed the role of low frequency (alpha, beta) activity in object processing.
      The target stimulus (i.e. object) was a small patch of a concentric grating of
      3c/ degrees , viewed eccentrically. The background stimulus was either a blank
      field or a concentric grating of 3c/ degrees  periodicity, viewed centrally. With
      patterned backgrounds, the target stimulus emerged--through rotation about its
      own centre--as a circular subsection of the background. Data were acquired using
      a 275-channel whole-head MEG system and analyzed using Synthetic Aperture
      Magnetometry (SAM), which allows one to generate images of task-related cortical
      oscillatory power changes within specific frequency bands. Significant
      oscillatory activity across a broad range of frequencies was evident at the V1/V2
      border, and subsequent analyses were based on a virtual electrode at this
      location. When the target was presented in isolation, we observed that: (i)
      contralateral stimulation yielded a sustained power increase in gamma activity;
      and (ii) both contra- and ipsilateral stimulation yielded near identical
      transient power changes in alpha (and beta) activity. When the target was
      presented against a patterned background, we observed that: (i) contralateral
      stimulation yielded an increase in high-gamma (>55 Hz) power together with a
      decrease in low-gamma (40-55 Hz) power; and (ii) both contra- and ipsilateral
      stimulation yielded a transient decrease in alpha (and beta) activity, though the
      reduction tended to be greatest for contralateral stimulation. The opposing power
      changes across different regions of the gamma spectrum with 'figure/ground'
      stimulation suggest a possible dual role for gamma rhythms in visual object
      coding, and provide general support of the binding-by-synchronization hypothesis.
      As the power changes in alpha and beta activity were largely independent of the
      spatial location of the target, however, we conclude that their role in object
      processing may relate principally to changes in visual attention.

PMID- 21194552
TI  - Inhibition of metastasis development by daily administration of ultralow doses of
      RNase A and DNase I.
AB  - Recent data on the involvement of miRNA and circulating tumor-derived DNA in
      regulation of tumorigenesis showed a great prospect for these molecules as a
      novel class of therapeutic targets and gave a new start for the study of enzymes
      cleaving nucleic acids as potential antitumor and antimetastatic agents. In the
      present paper using two murine tumor models with pulmonary or liver metastases we
      studied the antimetastatic potential of RNase A and DNase I and performed a
      search for possible molecular targets of the enzymes. Herein, we show for the
      first time that daily administration of ultralow doses of RNase A (0.5-50 MUg/kg)
      and DNase I (0.02-2.3 mg/kg) inhibits the development of metastasis to 60-90% and
      RNase A exerts 30% retardation of tumor growth. Remarkably, the increase in RNase
      A dose from 50 MUg/kg to 10mg/kg leads to a disappearance of antitumor and
      antimetastatic effects. Simultaneous treatment of tumor-bearing animals with
      RNase A and DNase I leads to an additive effect and results in almost total
      absence of metastases. The use of RNase A as an adjuvant in conjunction with
      conventional cytostatic cyclophosphamide results in a reliable enhancement of
      antitumor and antimetastatic effect of the therapy compared with the use of these
      agents individually. The search for possible molecular mechanism of
      antimetastatic effect of nucleases showed that daily administration of the
      enzymes reduced the pathologically increased level of extracellular nucleic acids
      and increased nuclease activity of the blood plasma of tumor-bearing mice back to
      the level of healthy animals. Thus, we unequivocally show that the proposed
      protocol of treatment of tumor-bearing animals with RNase A and DNase I has a
      general systemic and immunomodulatory effect, leads to a drastic suppression of
      metastasis development, and in perspective may become an effective component of
      intensive complex therapy of cancer.

PMID- 21194551
TI  - Block copolymer micelles with acid-labile ortho ester side-chains: Synthesis,
      characterization, and enhanced drug delivery to human glioma cells.
AB  - A new type of block copolymer micelles for pH-triggered delivery of poorly water
      soluble anticancer drugs has been synthesized and characterized. The micelles
      were formed by the self-assembly of an amphiphilic diblock copolymer consisting
      of a hydrophilic poly(ethylene glycol) (PEG) block and a hydrophobic
      polymethacrylate block (PEYM) bearing acid-labile ortho ester side-chains. The
      diblock copolymer was synthesized by atom transfer radical polymerization (ATRP)
      from a PEG macro-initiator to obtain well-defined polymer chain-length. The PEG-b
      PEYM micelles assumed a stable core-shell structure in aqueous buffer at
      physiological pH with a low critical micelle concentration as determined by
      proton NMR and pyrene fluorescence spectroscopy. The hydrolysis of the ortho
      ester side-chain at physiological pH was minimal yet much accelerated at mildly
      acidic pHs. Doxorubicin (Dox) was successfully loaded into the micelles at pH 7.4
      and was released at a much higher rate in response to slight acidification to pH
      5. Interestingly, the release of Dox at pH 5 followed apparently a biphasic
      profile, consisting of an initial fast phase of several hours followed by a
      sustained release period of several days. Dox loaded in the micelles was rapidly
      taken up by human glioma (T98G) cells in vitro, accumulating in the endolysosome
      and subsequently in the nucleus in a few hours, in contrast to the very low
      uptake of free drug at the same dose. The dose-dependent cytotoxicity of the Dox
      loaded micelles was determined by the MTT assay and compared with that of the
      free Dox. While the empty micelles themselves were not toxic, the IC(50) values
      of the Dox-loaded micelles were approximately ten-times (by 24h) and three-times
      (by 48h) lower than the free drug. The much enhanced potency in killing the multi
      drug-resistant human glioma cells by Dox loaded in the micelles could be
      attributed to high intracellular drug concentration and the subsequent pH
      triggered drug release. These results establish the PEG-b-PEYM block copolymer
      with acid-labile ortho ester side-chains as a novel and effective pH-responsive
      nano-carrier for enhancing the delivery of drugs to cancer cells.

PMID- 21194553
TI  - The visual coding of grip aperture shows an early but not late adherence to
      Weber's law.
AB  - An exemplar metric of goal-directed grasping (i.e., peak grip aperture) has been
      shown to be refractory to a psychophysical principle governing visuoperceptual
      estimations of object size (i.e., Weber's law). This dissociation suggests that
      vision for action and vision for perception are mediated by absolute and relative
      visual information, respectively. The present investigation examined whether
      aperture shaping elicits a unitary or process-dependent violation of Weber's law.
      Participants grasped differently sized objects (20, 30, 40, 50 and 60 mm of
      width) and just noticeable difference (JND) scores related to grip aperture were
      computed at the time of peak grip aperture as well as at normalized deciles of
      the response (i.e., 10-90% of grasping time). JNDs during the early and middle
      stages of the trajectory scaled to object size whereas values late in the
      trajectory (>50% of grasping time and including the time of peak grip aperture)
      did not. Thus, results show an early, but not late, adherence to Weber's law and
      indicate that movement planning and movement control are supported via relative
      and absolute visual information, respectively.

PMID- 21194554
TI  - Time dependence of coupling in frequency-scaled bimanual coordination.
AB  - Prior research has shown that fluctuations in the relative phase of bimanual
      coordination do not reflect a white Gaussian noise process. The present study
      furthered the examination of time-dependent properties in bimanual coordination
      by comparing the magnitude of relative phase variability and the degree of
      effector independence within the time domain. The original Kelso (1984) [10]
      bimanual frequency-scaling protocol was reproduced in which phase transitions
      from antiphase to in-phase were induced with increasing movement frequency. The
      results showed that as movement frequency was scaled-up the amount of relative
      phase variability increased and the effector movements became more dependent
      prior to the transition. This is consistent with previous modeling showing that
      stronger effector coupling can prevent the occurrence of phase transitions when
      long range correlations in relative phase are present. It appears that, as
      movement frequency is scaled up, increases in effector coupling strength minimize
      loss of pattern stability and delay the onset of phase transitions.

PMID- 21194555
TI  - Long-term gender behavioral vulnerability after nociceptive neonatal formalin
      stimulation in rats.
AB  - The role of sex and gender in accounting for individual pain behaviors is poorly
      understood. The present study was conducted to determine whether neonatal
      nociceptive stimuli at postnatal day 1 (PD1) in rats would lead to a differential
      behavioral impact based on gender. Animals were divided in 4 groups according to
      treatment (two injections of 4% formalin into the pad of right paws at PD1 or
      control) and gender. The sensory threshold and cognition tests were performed in
      adult rats using the hot plate, open field, elevated plus maze and forced swim
      tests. The number of paw licks was higher in females and in formalin-treated rats
      (P=0.02), but without interaction between gender and treatment. Exploratory
      activity was reduced in males (P<0.01), especially in the nociceptive group
      (P<0.01). Anxiety levels were higher in the female-nociceptive group (P<0.05).
      Depression-like behavior was more evident among females, independent of
      treatment. We concluded that a single acute nociceptive stimulation early in
      development does not affect nociception and depressive behaviors, but is able to
      alter the exploratory behavior and anxiety levels in adulthood in a gender
      specific manner.

PMID- 21194556
TI  - Leptin controls ketone body utilization in hypothalamic neuron.
AB  - Leptin is an appetite-controlling peptide secreted from adipose tissue.
      Previously, we showed that the gene expression of acetoacetyl-CoA synthetase
      (AACS), the ketone body-utilizing enzyme for lipid synthesis, was suppressed by
      leptin deficiency-induced obesity in white adipose tissue. In this study, to
      clarify the effects of leptin on ketone body utilization in the central nervous
      system, we examined the effects of leptin signaling on AACS expression. In situ
      hybridization analysis of ob/ob and db/db mice revealed that AACS mRNA level was
      reduced by leptin deficiency in the arcuate nucleus (Arc) and ventromedial
      hypothalamic nucleus (VMH) in hypothalamus but not in other brain regions.
      Moreover, AACS mRNA level was increased by leptin treatment both in primary
      cultured neural cells and in N41 neural-like cells. In N41 cells, AACS level was
      decreased by AMPK inducer but increased by AMPK inhibitor. These results suggest
      that the up-regulation of AACS expression by leptin is due to the suppression of
      AMPK activity via neural leptin signaling and that the deficiency of this
      regulation may be responsible for neurological disorders in central appetite
      control.

PMID- 21194557
TI  - Nicotine and 17beta-estradiol produce an antidepressant-like effect in female
      ovariectomized rats.
AB  - Nicotine and estrogen may influence depressive behavior in women. In this study,
      we sought to determine whether nicotine (NIC), alone and in combination with
      17beta-estradiol (E(2)), might influence depressive characteristics of female
      rats in the forced swim test (FST). Ovariectomized adult female Sprague-Dawley
      rats (n = 8/group) received subcutaneous (s.c.) injections of nicotine, E(2) or
      the combination (NIC: 0.2 mg/kg, bw and E(2): 10 MUg) before the FST. Controls
      received saline and/or corn oil. Locomotor activity was also assessed. Acute
      administration of nicotine significantly reduced immobility in the FST. Acute
      administration of E(2) also decreased immobility. The combination of nicotine
      (0.2 mg/kg) and E(2) (10 MUg) significantly reduced immobility; however, this
      reduction was not greater than either agent administered alone. No differences in
      locomotor activity were detected among the treatment groups. Acute administration
      of nicotine and E(2), alone and in combination, significantly decreased
      immobility of ovx rats in the FST, suggesting an antidepressant-like effect of
      these two agents in this model. However, the combination of E(2) and nicotine did
      not have any further reduction, indicating a lack of an additive or synergistic
      effect. Results from this study suggest that agents that target nicotinic
      acetylcholine receptors and estrogen receptors may be beneficial in alleviating
      depressive symptoms in women during periods of low estrogen levels.

PMID- 21194558
TI  - Human umbilical cord Wharton's jelly-derived mesenchymal stem cells differentiate
      into a Schwann-cell phenotype and promote neurite outgrowth in vitro.
AB  - Cell-based therapy has achieved promising functional recovery for peripheral
      nerve repair. Although Schwann cells (SCs) and bone marrow derived mesenchymal
      stromal cells (BM-MSCs) are the main cell source for nerve tissue engineering,
      the clinical application is limited because of donor site morbidity, the invasive
      procedure, and the decreased number of SCs and BM-MSCs. Wharton's jelly-derived
      mesenchymal stem cells (WJMSCs) could be a promising cell source for nerve tissue
      engineering because they are easily accessible and their use has no ethical
      issues. We investigated the phenotypic, molecular and functional characteristics
      of WJMSCs differentiated along a Schwann-cell lineage. Cultured WJMSCs were
      isolated from human umbilical cord, and the undifferentiated WJMSCs were
      confirmed by the detection of MSC-specific cell-surface markers. WJMSCs treated
      with a mixture of glial growth factors (basic fibroblast growth factor, platelet
      derived growth factor and forskolin) adopted a spindle-like morphology similar to
      SCs. Immunocytochemical staining, RT-PCR analysis, and Western blot analysis
      revealed that the treated cells expressed the glial markers glial fibrillary
      acidic protein, p75, S100 and P0 and indicative of differentiation. On co-culture
      with dorsal root ganglia neurons, the differentiated WJMSCs enhanced the number
      of sprouting neurites and neurite length in dorsal root ganglia neurons.
      Furthermore, using enzyme-linked immunosorbent assay and RT-PCR methodology, we
      found differentiated WJMSCs secrete and express neurotrophic factors, including
      brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and
      neurotrophin-3 (NT-3). Quantification of neurite outgrowth from PC12 cells grown
      in differentiated WJMSCs-conditioned media demonstrates that the neurite length
      is significantly more than control medium and undifferentiated WJMSCs group.
      WJMSCs can be differentiated into cells that are Schwann-like in terms of
      morphologic features, phenotype, and function and could be suitable Schwann-cell
      substitutes for nerve repair in clinical applications.

PMID- 21194559
TI  - Molecular analysis and functions of p53R2 in zebrafish.
AB  - p53R2 is a newly identified small subunit of ribonucleotide reductase and plays a
      pivotal role in the supply of dNTPs for genomic DNA repair and mitochondrial DNA
      synthesis, but little is known about its functions in zebrafish. Herein, we
      obtained the cDNA of zebrafish p53R2 that shares 72.8% and 72.5% amino acid
      identities with human p53R2 and zebrafish R2, respectively. Residues crucial for
      enzymatic activity are highly conserved among p53R2 proteins from different
      species. p53R2 in zebrafish was maternally expressed, its transcripts were
      detected in developing embryos and all adult tissues examined. A 250-bp minimal
      promoter upstream of the translational initiation site was identified to drive
      basal expression of p53R2 in a p53-independent manner. Expression of p53R2 was
      induced by DNA-damaging reagents CPT or MMS, but suppressed by p53-knockdown in
      zebrafish embryos. Moreover, p53R2 was mainly distributed in the cytoplasm of
      cells under normal condition and upon DNA damage. Furthermore, overexpression of
      p53R2 attenuated apoptosis of embryonic cells caused by CPT or MMS treatment and
      protected developing embryos from death. Therefore, functions of p53R2 in
      zebrafish are closely associated with its activity in DNA repair and synthesis.

PMID- 21194560
TI  - Raman mapping of pharmaceuticals.
AB  - Raman spectroscopy may be implemented through a microscope to provide fine scale
      axial and lateral chemical maps. The molecular structure of many drugs makes
      Raman spectroscopy particularly well suited to the investigation of
      pharmaceutical systems. Chemometric methods currently used to assess bulk Raman
      spectroscopic data are typically applied to Raman mapping data from
      pharmaceuticals; few reports exist where the spatial information inherent to a
      mapped dataset is used for the calculation of chemical maps. Both univariate and
      multivariate methods have been applied to Raman mapping data to determine the
      distribution of active pharmaceutical ingredients (APIs) in tablets, solid
      dispersions for increased solubility and controlled release devices. The ability
      to axially (depth) profile using Raman mapping has been used in studies of API
      penetration through membranes, cellular uptake of drug delivery liposomes, and
      initial API distribution and subsequent elution from coatings of medical devices.
      New instrumental developments will increase the efficiency of Raman mapping and
      lead to greater utilisation of Raman mapping for analyses of pharmaceutical
      systems.

PMID- 21194561
TI  - A tribute to Jeffery A. Winer.

PMID- 21194562
TI  - The effect of bacteria on diatom community structure--the 'antibiotics' approach.
AB  - To investigate the effect of bacteria on diatoms at the community level, sediment
      samples from an intertidal tropical environment were treated with penicillin (a
      beta-lactam antibiotic that can affect diatoms only through bacteria).
      Streptomycin (an aminoglycoside) and chloramphenicol, antibiotics that can
      potentially affect protein synthesis in diatom organelles and photosynthesis,
      were also used for comparison. The changes in diatom community structure and the
      resistant and tolerant bacterial fractions were analyzed through microscopy,
      culture techniques and denaturing gradient gel electrophoresis. The reduction in
      bacterial abundance when treated with penicillin resulted in suppression of
      Amphora coffeaeformis, a dominant diatom in the study area. The bacterial
      community preferred the 'tolerance' strategy over 'resistance' in response to
      treatment with penicillin; these changes in bacterial dynamics were probably
      linked to concurrent changes in diatom community structure. The observations with
      penicillin differed from those with streptomycin that did not seem to
      significantly affect diatoms, and chloramphenicol, which consistently inhibited
      diatoms. Overall, the results of this study highlight the significance of
      bacteria in structuring benthic diatom communities and call for the inclusion of
      the 'antibiotics' approach in studies addressing diatom-bacterial interactions at
      the community level.

PMID- 21194564
TI  - Role of thyroid receptor beta in lipid metabolism.
AB  - Thyroid hormones (THs) exert their actions by binding to thyroid hormone
      receptors (TRs) and thereby affect tissue differentiation, development, and
      metabolism in most tissues. TH-deficiency creates a less favorable lipid profile
      (e.g. increased plasma cholesterol levels), whereas TH-excess is associated with
      both positive (e.g. reduced plasma cholesterol levels) and negative (e.g.
      increased heart rate) effects. TRs are encoded by two genes, THRA and THRB,
      which, by alternative splicing, generate several isoforms (e.g. TRalpha1,
      TRalpha2, TRbeta1, and TRbeta2). TRalpha, the major TR in the heart, is crucial
      for heart rate and for cardiac contractility and relaxation, whereas TRbeta1, the
      major TR in the liver, is important for lipid metabolism. Selective modulation of
      TRbeta1 is thus considered as a potential therapeutic target to treat
      dyslipidemia without cardiac side effects. Several selective TH analogs have been
      tested in preclinical studies with promising results, but only a few of these
      compounds have so far been tested in clinical studies. This review focuses on the
      role of THs, TRs, and selective and non-selective TH analogs in lipid metabolism.
      This article is part of a Special Issue entitled: Translating nuclear receptors
      from health to disease.

PMID- 21194565
TI  - Role of nuclear receptors for bile acid metabolism, bile secretion, cholestasis,
      and gallstone disease.
AB  - Nuclear receptors (NRs) play a key role in the transcriptional control of
      critical steps of hepatobiliary transport and phase I/II metabolism of endo- and
      xenobiotics such as bile acids and drugs. Apart from these metabolic roles, NRs
      may also play a key role in the control of hepatic inflammation. Hereditary and
      acquired alterations of NRs contribute to our understanding of the pathogenesis
      of cholestasis and gallstone disease. Moreover, NRs may represent attractive drug
      targets for these disorders. This article is part of a Special Issue entitled:
      Translating nuclear receptors from health to disease.

PMID- 21194563
TI  - Emerging actions of the nuclear receptor LRH-1 in the gut.
AB  - Liver receptor homolog-1 (NR5A2) is a nuclear receptor originally identified in
      the liver and mostly known for its regulatory role in cholesterol and bile acid
      homeostasis. More recently, liver receptor homolog-1 has emerged as a key
      regulator of intestinal function, coordinating unanticipated actions, such as
      cell renewal and local immune function with important implications to common
      intestinal diseases, including colorectal cancer and inflammatory bowel disease.
      Unlike most of the other nuclear receptors, liver receptor homolog-1 acts as a
      constitutively active transcription factor to drive the transcription of its
      target genes. Liver receptor homolog-1 activity however is to a major extent
      regulated by different corepressors and posttranslational modifications, which
      may account for its tissue-specific functions. This review will provide an update
      on the molecular aspects of liver receptor homolog-1 action and focus on some
      emerging aspects of its function in normal and diseased gut. This article is part
      of a Special Issue entitled: Translating nuclear receptors from health to
      disease.

PMID- 21194566
TI  - The thyroid hormones and their nuclear receptors in the gut: from developmental
      biology to cancer.
AB  - The thyroid hormones control the development and the homeostasis of several
      organs in vertebrates. Their actions depend, for the most part, on nuclear
      receptors, the TRs, which are transcription factors whose activity is modulated
      by the hormone T3. The gastrointestinal tract is a well characterized target of
      thyroid hormones and TRs, as extensively described in the literature. In fact,
      its remodeling in amphibians during thyroid hormone-dependent metamorphosis is
      well characterized at the cellular and the molecular levels. However, whereas a
      great attention has been paid to the nervous system and to cardiac development
      and physiology, the function of thyroid hormones and TRs in the mammalian
      gastrointestinal tract has been, until recently, underestimated. Several studies
      have described an important conservation of this hormonal signal during
      intestinal development and have suggested that it may play a role in stem cell
      physiology in both amphibians and mammals. These findings show the importance of
      the thyroid hormones and TRs, whose homologous actions are maintained across
      species. In the present review, we summarize the most recent data on this issue,
      starting from work that has been conducted on amphibian metamorphosis to results
      on postnatal development, homeostasis, and tumorigenesis in mammals. This article
      is part of a Special Issue entitled: Translating nuclear receptors from health to
      disease.

PMID- 21194567
TI  - Mesenchymal stem cells together with mycophenolate mofetil inhibit antigen
      presenting cell and T cell infiltration into allogeneic heart grafts.
AB  - Donor-derived mesenchymal stem cells (MSC) can induce long-term acceptance in a
      rat heart transplantation model when injected prior to transplantation in
      combination with mycophenolate mofetil (MMF). In contrast, MSC alone cause
      accelerated graft rejection. To better understand these conflicting data we
      studied the effects of MSC and MMF on lymphocyte populations in heart allografts
      and secondary lymphatic organs. Allogeneic MSC injected prior to transplantation
      are immunogenic in this model because activated CD4+ and CD8+ cells emerged
      earlier in secondary lymphatic organs of MSC- and MSC/MMF-treated animals,
      compared to animals not treated with MSC. Consequently T cells infiltrated the
      grafts of MSC-only treated animals promptly causing accelerated graft rejection.
      However, few T cells or antigen-presenting cells (APC) infiltrated the grafts of
      animals treated with MSC and MMF. Consistent with this finding, intercellular
      adhesion molecule 1 (ICAM-1) and E-selectin was down-regulated exclusively in
      MSC/MMF-treated grafts, indicating that MSC together with MMF interfere with
      endothelial activation. Additionally, the presence of interferon-gamma (IFN
      gamma) enhanced MSC capabilities to suppress T cell proliferation in vitro.
      Interestingly, MMF did not influence serum IFN-gamma levels in vivo. Together,
      our data indicate that MSC pre-activate T cells, but co-treatment with MMF
      eliminates these T cells, decreases intragraft APC and T cell trafficking by
      inhibiting endothelial activation, and allows IFN-gamma stimulation of
      suppressive MSC.

PMID- 21194568
TI  - Transcription factors expressed in olfactory bulb local progenitor cells revealed
      by genome-wide transcriptome profiling.
AB  - The local progenitor population in the olfactory bulb (OB) gives rise to mitral
      and tufted projection neurons during embryonic development. In contrast, OB
      interneurons are derived from sources outside the bulb where neurogenesis
      continues throughout life. While many of the genes involved in OB interneuron
      development have been characterized, the genetic pathways driving local
      progenitor cell differentiation in this tissue are largely unknown. To better
      understand this process, we used transcriptional profiling to monitor gene
      expression of whole OB at daily intervals from embryonic day 11 through birth,
      generating a compendium of gene expression encompassing the major developmental
      events of this tissue. Through hierarchical clustering, bioinformatics analysis,
      and validation by RNA in situ hybridizations, we identified a large number of
      transcription factors, DNA binding proteins, and cell cycle-related genes
      expressed by the local neural progenitor cells (NPCs) of the embryonic OB.
      Further in silico analysis of transcription factor binding sites identified an
      enrichment of genes regulated by the E2F-Rb pathway among those expressed in the
      local NPC population. Together these results provide initial insights into the
      molecular identity of the OB local NPC population and the transcription factor
      networks that may regulate their function.

PMID- 21194569
TI  - Altered dynamic coupling of lateral occipital complex during visual perception in
      schizophrenia.
AB  - INTRODUCTION: There is mounting evidence that visual perception abnormalities in
      schizophrenia are partly explained by a dysfunction of the lateral occipital
      complex (LO). We previously demonstrated that schizophrenia patients had broader
      topography and reduced magnitude of activity of LO. However, the functional
      connectivity of LO with other brain regions during visual perception has not been
      directly investigated in schizophrenia. MATERIALS AND METHODS: Eighteen patients
      with schizophrenia and eighteen matched controls performed a backward masking
      task during functional magnetic resonance imaging (fMRI). Stimulus onset
      asynchronies were manipulated to change the level of target visibility. To
      examine connectivity with LO function we conducted psychophysiological
      interactions (PPI) analyses using: 1) a region of interest (ROI) approach and 2)
      a whole brain analysis. ROIs were defined based on a contrast of trials on which
      a target was presented versus null trials in which no stimuli were presented.
      RESULTS: Eleven ROIs were identified. Both groups showed similar strength of
      coupling between LO and the 11 ROIs when visibility was not taken into account.
      Healthy controls showed clear changes in coupling between LO and prefrontal and
      parietal regions as a function of target visibility (higher coupling with more
      visible targets). In comparison, patients showed reduced dynamic coupling with LO
      in the right superior frontal gyrus (significant after correcting for multiple
      comparisons) and a trend for reduced coupling in the left precuneus and left
      inferior frontal regions. Whole brain analysis identified additional regions that
      showed dynamic coupling with LO in healthy controls, but not in patients.
      DISCUSSION: The increased coupling between LO and higher-level parietal and
      prefrontal regions during visual awareness in healthy controls likely reflects
      visual reentrant processing. The lack of modulation of coupling between LO and
      key prefrontal and parietal regions found in schizophrenia may partly reflect
      abnormalities in LO tuning. The altered LO coupling may contribute to visual
      perception abnormalities in schizophrenia.

PMID- 21194570
TI  - Negative edges and soft thresholding in complex network analysis of resting state
      functional connectivity data.
AB  - Complex network analyses of functional connectivity have consistently revealed
      non-random (modular, small-world, scale-free-like) behavior of hard-thresholded
      networks constructed from the right-tail of the similarity histogram. In the
      present study we determined network properties resulting from edges constrained
      to specific ranges across the full correlation histogram, in particular the left
      (negative-most) tail, and their dependence on the confound signal removal
      strategy employed. In the absence of global signal correction, left-tail networks
      comprised predominantly long range connections associated with weak correlations
      and were characterized by substantially reduced modularity and clustering,
      negative assortativity and gamma<1 Deconvolution of specific confound signals
      (white matter, CSF and motion) resulted in the most robust within-subject
      reproducibility of global network parameters (ICCs~0.5). Global signal removal
      altered the network topology in the left tail, with the clustering coefficient
      and assortativity converging to zero. Networks constructed from the absolute
      value of the correlation coefficient were thus compromised following global
      signal removal since the different right-tail and left-tail topologies were
      mixed. These findings informed the construction of soft-thresholded networks,
      replacing the hard thresholding or binarization operation with a continuous
      mapping of all correlation values to edge weights, suppressing rather than
      removing weaker connections and avoiding issues related to network fragmentation.
      A power law adjacency function with beta=12 yielded modular networks whose
      parameters agreed well with corresponding hard-thresholded values, that were
      reproducible in repeated sessions across many months and evidenced small-world
      like and scale-free-like properties.

PMID- 21194571
TI  - Translation of flecainide- and mexiletine-induced cardiac sodium channel
      inhibition and ventricular conduction slowing from nonclinical models to
      clinical.
AB  - INTRODUCTION: Nonclinical in vivo models used for cardiovascular safety testing
      have not previously been studied for their sensitivity for detection of
      conduction slowing resulting from cardiac sodium channel block. The goal of this
      study was to examine the sensitivity of in vivo models to cardiac sodium channel
      block, and translation of the effect from in vitro to in vivo models using sodium
      channel inhibitors flecainide and mexiletine; flecainide, but not mexiletine is
      commonly associated with QRS complex prolongation in humans. METHODS: Inhibition
      of cloned cardiac sodium channels (hNav1.5) was studied using the IonWorks
      platform. Conduction slowing was measured in vitro in the rabbit isolated
      ventricular wedge (RVW) and in vivo in the conscious telemetered rat and dog, and
      anaesthetised dog. RESULTS: Flecainide and mexiletine inhibited hNav1.5 channels
      with IC50 values of 10.7 and 67.2 MUM respectively. In the RVW, QRS was increased
      by flecainide at 60 bpm, and at 120bpm, there was an increased effect of both
      drugs. In conscious rats, flecainide significantly increased QRS complex
      duration; mexiletine had no significant effect, but there was an increase at the
      highest dose in 4/6 animals. QRS complex was increased by flecainide and
      mexiletine in anaesthetised dogs but this was not statistically significant; in
      conscious dog, only flecainide produced a significant increase in QRS complex.
      DISCUSSION: When compared to clinical data, effects of flecainide and mexiletine
      in RVW and conscious dog compared well with effects in patients and healthy
      volunteers in terms of sensitivity. The anaesthetised dog was least sensitive for
      detection of changes in QRS. All assays showed some differentiation between the
      expected conduction slowing activity of flecainide and mexiletine. Based on these
      data, RVW and conscious dog were most predictive for effects of compounds on QRS
      complex and cardiac conduction.

PMID- 21194572
TI  - On the mutation rates of spoligotypes and variable numbers of tandem repeat loci
      of Mycobacterium tuberculosis.

PMID- 21194573
TI  - Dragon exploratory system on hepatitis C virus (DESHCV).
AB  - Even though hepatitis C virus (HCV) cDNA was characterized about 20 years ago,
      there is insufficient understanding of the molecular etiology underlying HCV
      infections. Current global rates of infection and its increasingly chronic
      character are causes of concern for health policy experts. Vast amount of data
      accumulated from biochemical, genomic, proteomic, and other biological analyses
      allows for novel insights into the HCV viral structure, life cycle and functions
      of its proteins. Biomedical text-mining is a useful approach for analyzing the
      increasing corpus of published scientific literature on HCV. We report here the
      first comprehensive HCV customized biomedical text-mining based online web
      resource, dragon exploratory system on hepatitis C virus (DESHCV), a biomedical
      text-mining and relationship exploring knowledge base was developed by exploring
      literature on HCV. The pre-compiled dictionaries existing in the dragon
      exploratory system (DES) were enriched with biomedical concepts pertaining to HCV
      proteins, their name variants and symbols to make it suitable for targeted
      information exploration and knowledge extraction as focused on HCV. A list of
      32,895 abstracts retrieved via PubMed database using specific keywords searches
      related to HCV were processed based on concept recognition of terms from several
      dictionaries. The web query interface enables retrieval of information using
      specified concepts, keywords and phrases, generating text-derived association
      networks and hypotheses, which could be tested to identify potentially novel
      relationship between different concepts. Such an approach could also augment
      efforts in the search for diagnostic or even therapeutic targets. DESHCV thus
      represents online literature-based discovery resource freely accessible for
      academic and non-profit users via http://apps.sanbi.ac.za/DESHCV/ and its mirror
      site http://cbrc.kaust.edu.sa/deshcv/.

PMID- 21194574
TI  - Plasma-assisted surface modification of organic biopolymers to prevent bacterial
      attachment.
AB  - Despite many synthetic biomaterials having physical properties that are
      comparable or even superior to those of natural body tissues, they frequently
      fail due to the adverse physiological reactions they cause within the human body,
      such as infection and inflammation. The surface modification of biomaterials is
      an economical and effective method by which biocompatibility and biofunctionality
      can be achieved while preserving the favorable bulk characteristics of the
      biomaterial, such as strength and inertness. Amongst the numerous surface
      modification techniques available, plasma surface modification affords device
      manufacturers a flexible and environmentally friendly process that enables
      tailoring of the surface morphology, structure, composition, and properties of
      the material to a specific need. There are a vast range of possible applications
      of plasma modification in biomaterial applications, however, the focus of this
      review paper is on processes that can be used to develop surface morphologies and
      chemical structures for the prevention of adhesion and proliferation of
      pathogenic bacteria on the surfaces of in-dwelling medical devices. As such, the
      fundamental principles of bacterial cell attachment and biofilm formation are
      also discussed. Functional organic plasma polymerised coatings are also discussed
      for their potential as biosensitive interfaces, connecting inorganic/metallic
      electronic devices with their physiological environments.

PMID- 21194575
TI  - Lung disease in FLNA mutation: confirmatory report.
AB  - Recently in this journal, Masurel-Paulet et al. reported the association between
      pulmonary disease and a mutation in X-linked FLNA in a male patient. We confirm
      this association in a female patient, showing that this complication is not sex
      specific. Our patient has a FLNA missense mutation (c.220G > A) and presented
      with cerebral periventricular nodular heterotopia, cardiovascular abnormalities,
      and pulmonary disease consisting of lobar emphysema of the right middle pulmonary
      lobe with severe malacia of the right sided bronchus intermedius. Surgical
      resection of the right middle lobe was necessary and she had long-term oxygen
      dependency. Symptoms improved with age.

PMID- 21194576
TI  - Exploring the spectrum of incretin therapies: the potential for optimizing
      patient outcomes. Introduction.

PMID- 21194577
TI  - Initial combination therapy for type 2 diabetes mellitus: is it ready for prime
      time?
AB  - The increased prevalence of type 2 diabetes mellitus is primarily being driven by
      the increasing global rates of overweight/obesity. Given the magnitude of this
      epidemic, we can expect these metabolic abnormalities to play an increasing role
      in the development of cardiovascular disease. In a pathophysiologic sense, type 2
      diabetes is a multiorgan, multifactorial condition, characterized by beta-cell
      dysfunction, insulin resistance in peripheral tissues and the liver, defective
      incretin activity, and elevated levels of free fatty acids and proinflammatory
      mediators. Despite the considerable burden of disease associated with type 2
      diabetes, most patients are not at, or are unable to achieve, recommended
      glycemic control guideline targets. In part, this is because of the relentlessly
      progressive nature of the disease, but it may also be attributable to the current
      diabetes treatment paradigm, which is characterized by ineffective lifestyle
      interventions, followed by monotherapy and frequent early treatment failure with
      prolonged periods of elevated glucose as a consequence of clinical inertia. Thus,
      it is most appropriate to rethink the current treatment paradigm for type 2
      diabetes in the context of a more aggressive initial therapy; specifically with
      early initiation of combination therapy. Our current understanding of the complex
      pathophysiology of the disease and the progressive deterioration in glycemic
      control over time supports the philosophy of earlier intervention with a more
      comprehensive initial therapy. Thus, while control of hyperglycemia remains the
      paramount goal, focusing on the underlying pathophysiology of type 2 diabetes is
      increasingly becoming the therapeutic strategy, with the aim of potentially
      providing disease modification. Although this is a logical approach, it remains
      to be demonstrated that early combination therapy will result in disease
      modification in a clinical setting. Not surprisingly, the incretin-based
      therapies have gained a great deal of attention in the context of being a
      component of initial combination therapy, given their potential beneficial
      effects on beta-cell function with lowered risk of weight gain and hypoglycemia.

PMID- 21194578
TI  - Incretin-based therapies for type 2 diabetes mellitus: properties, functions, and
      clinical implications.
AB  - The incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and
      glucagonlike peptide-1 (GLP-1), which are secreted by cells of the
      gastrointestinal tract in response to meal ingestion, exercise important
      glucoregulatory effects, including the glucose-dependent potentiation of insulin
      secretion by pancreatic beta-cells. Research on the defective incretin action in
      type 2 diabetes mellitus suggests that the observed loss of insulinotropic
      activity may be due primarily to a decreased responsiveness of beta-cells to GIP.
      GLP-1 does retain efficacy, albeit not at physiologic levels. Accordingly,
      augmentation of GLP-1 is a logical therapeutic strategy to ameliorate this
      deficiency, although the short metabolic half-life of the native hormone renders
      direct infusion impractical. GLP-1 receptor agonists that resist degradation by
      the enzyme dipeptidyl peptidase-4 (DPP-4) and have protracted-action kinetics
      have been developed, and DPP-4 inhibitors that slow the enzymatic cleavage of
      native GLP-1 provide alternative approaches to enhancing incretin-mediated
      glucose control. However, GLP-1 receptor agonists and DPP-4 inhibitors are
      premised on highly divergent mechanisms of action. DPP-4 is ubiquitously
      expressed in many tissues and is involved in a wide range of physiologic
      processes in addition to its physiologic influence on incretin hormone biological
      activity. GLP-1 receptor agonists provide a pharmacologic level of GLP-1 receptor
      stimulation, whereas DPP-4 inhibitors appear to increase levels of circulating
      GLP-1 to within the physiologic range. This article examines the physiology of
      the incretin system, mechanistic differences between GLP-1 receptor agonists and
      DPP-4 inhibitors used as glucose-lowering agents in the treatment of type 2
      diabetes, and the implications of these differences for treatment. The results of
      recent head-to-head trials are reviewed, comparing the effects of incretin-based
      therapies on a range of clinical parameters, including glycemia, beta-cell
      function, weight, and cardiovascular function.

PMID- 21194579
TI  - Cardiovascular comorbidities of type 2 diabetes mellitus: defining the potential
      of glucagonlike peptide-1-based therapies.
AB  - The global epidemic of diabetes mellitus (~95% type 2 diabetes) has been fueled
      by a parallel increase in obesity and overweight. Together, these metabolic
      disease epidemics have contributed to the increasing incidence and prevalence of
      cardiovascular disease. The accumulation of metabolic and cardiovascular risk
      factors in patients with type 2 diabetes--risk factors that may exacerbate one
      another--complicates treatment. Inadequate treatment, treatment that fails to
      achieve goals, increases the risk for cardiovascular morbidity and mortality.
      From a clinical perspective, type 2 diabetes is a cardiovascular disease, an
      observation that is supported by a range of epidemiologic, postmortem, and
      cardiovascular imaging studies. Vascular wall dysfunction, and particularly
      endothelial dysfunction, has been posited as a "common soil" linking dysglycemic
      and cardiovascular diseases. Vascular wall dysfunction promoted by environmental
      triggers (e.g., sedentary lifestyle) and metabolic triggers (chronic
      hyperglycemia, obesity) has been associated with the upregulation of reactive
      oxygen species and chronic inflammatory and hypercoagulable states, and as such
      with the pathogenesis of type 2 diabetes, atherosclerosis, and cardiovascular
      disease. Glucagon-like peptide-1 (GLP)-1, an incretin hormone, and synthetic GLP
      1 receptor agonists represent promising new areas of research and therapeutics in
      the struggle not only against type 2 diabetes but also against the cardiovascular
      morbidity and mortality associated with type 2 diabetes. In a number of small
      trials in humans, as well as in preclinical and in vitro studies, both native GLP
      1 and GLP-1 receptor agonists have demonstrated positive effects on a range of
      cardiovascular disease pathologies and clinical targets, including such markers
      of vascular inflammation as high-sensitivity C-reactive protein, plasminogen
      activator inhibitor-1, and brain natriuretic peptide. Reductions in markers of
      dyslipidemia such as elevated levels of triglycerides and free fatty acids have
      also been observed, as have cardioprotective functions. Larger trials of longer
      duration will be required to confirm preliminary findings. In large human trials,
      GLP-1 receptor agonists have been associated with significant reductions in both
      blood pressure and weight.

PMID- 21194580
TI  - Incretin-based therapies in complex patients: practical implications and
      opportunities for maximizing clinical outcomes: a discussion with Dr. Vivian A.
      Fonseca.
AB  - Elderly patients and patients with renal impairment present unique challenges in
      the management of diabetes mellitus. Impaired renal function is a common
      comorbidity (or complication) associated with type 2 diabetes, as well as a
      complicating factor in the treatment of the disease. Renal insufficiency, which
      can result in elevated plasma concentrations of pharmaceutical agents, may
      preclude the use of some antihyperglycemic medications and require that the
      dosages of others be reduced. Failure to select and dose medications carefully in
      these patients may increase the risk of hypoglycemia and other adverse effects.
      For example, elevated plasma concentrations of some sulfonylureas may increase
      the risk of hypoglycemia. Because patients with chronic renal insufficiency tend
      to retain fluids, treatment with a thiazolidinedione--a class of agents
      associated with fluid retention--may exacerbate the risk of edema. Older patients
      with type 2 diabetes--like patients with renal insufficiency an important and
      populous subgroup--also have issues with therapy selection and dosing regimens.
      As a result of the effects of aging on kidney function, older patients may also
      be subject to elevated plasma levels with consequent additional risk of
      hypoglycemia and other adverse events. Because older patients tend to be treated
      with multiple medications for multiple comorbidities, it becomes challenging to
      design regimens that avoid or reduce the risk of drug-drug interactions. For both
      older patients and patients with chronic renal insufficiency, the most important
      drug-related adverse effect to avoid is hypoglycemia. Accordingly, incretin-based
      agents have an advantage because they are unlikely to cause hypoglycemia.

PMID- 21194581
TI  - Proximal contact loss between implant-supported prostheses and adjacent natural
      teeth: a clinical report.
AB  - There is limited knowledge about the changes that proximal contacts between
      implant-supported prostheses and adjacent teeth undergo over time. This report
      describes the management of a clinical situation with the loss of proximal
      contact between implant-supported prostheses and adjacent natural teeth in a
      partially edentulous patient.

PMID- 21194582
TI  - The influence of cantilever length and implant inclination on stress distribution
      in maxillary implant-supported fixed dentures.
AB  - STATEMENT OF PROBLEM: The benefits and limitations of jaw treatments with tilted
      versus vertical implants, as well as prosthesis design with and without posterior
      cantilevers, have been extensively discussed. However, biomechanical advantages
      associated with cantilevers in fixed dentures (FDs) and tilted implants in the
      maxillae are less well documented. PURPOSE: The purpose of this study was to
      compare and analyze, via 3-dimensional (3-D) finite element analysis, stresses
      transmitted to tilted versus vertical implants and the surrounding periimplant
      bone in the maxillae. MATERIAL AND METHODS: A 3-D edentulous maxillary model was
      created using customized computer software (FEMAP 8.3). Four implants were
      virtually placed in the premaxilla and splinted with an FD. Keeping the
      prosthesis length constant, 4 different configurations were evaluated with the
      distal implants inclined 0, 15, 30, and 45 degrees; cantilever extensions were
      13, 9, 5, and 0 mm, respectively. A vertical load (150 N) was applied to the
      distal portion of the posterior cantilevers. Von Mises' stress values transmitted
      to periimplant bone and at the metal framework of FDs on implants were evaluated
      in cancellous and cortical bone. RESULTS: The maximum stresses recorded in
      periimplant bone for the vertical implants were 75.0 MPa (distal implants), 35.0
      MPa (mesial implants), and 95.0 MPa for the metal frameworks. Tilted distal
      implants, with consequent reduction of the posterior cantilevers, resulted in
      decreased stress values for all of the variables: -12.9%, -18.3%, and -11.5% for
      the 15-degree configuration; -47.5%, -52.6%, and -31.3% for the 30-degree
      configuration; and -73.5%, -77.7%, and -85.6% for the 45-degree configuration
      CONCLUSIONS: Finite element analysis data regarding rehabilitation of atrophic
      maxillae revealed that tilted distal implants, rigidly splinted with an FD,
      decrease stress in the periimplant bone and frameworks. This treatment modality
      seems to be a valid therapeutic alternative to conventional maxillary fixed
      complete prostheses supported by vertical dental implants with posterior
      cantilevers.

PMID- 21194583
TI  - Mechanical behavior of ceramic veneer in zirconia-based restorations: a 3-
      dimensional finite element analysis using microcomputed tomography data.
AB  - STATEMENT OF PROBLEM: The fracture or chipping of ceramic veneers is a common
      problem for zirconia-based restorations. PURPOSE: This study evaluated the stress
      distribution in the veneer of a maxillary central incisor restored with a
      complete crown using a zirconia core with a feldspathic ceramic veneer,
      simulating an incomplete bond between the veneer and zirconia substructure.
      MATERIAL AND METHODS: Based on a microcomputed tomography of a maxillary central
      incisor, 3 finite element models (M) for a complete crown were developed: Mf, a
      complete crown based on feldspathic ceramic; Mlz, a zirconia-based complete crown
      with a complete bond at the zirconia/veneer interface; and Mnzl, similar to Mlz,
      but with an incomplete bond at the zirconia/veneer interface created by using a
      contact element with a frictional coefficient of 0.3. A distributed load of 1 N
      was applied to the lingual surface at 45 degrees to the long axis of the tooth.
      RESULTS: The zirconia core in the Mnzl model showed peak stresses for maximum
      principal stress (sigma(max)) and shear stress of 9.02 and 8.81 MPa,
      respectively. The ceramic veneer in the Mnlz model showed peak stresses for
      sigma(max), minimum principal stress (compressive), and von Mises stresses of 5.4
      MPa, 61.23 MPa, and 35.19 MPa, respectively. CONCLUSIONS: The incomplete bond
      increased the sigma(max) in the ceramic veneer in comparison to the perfect bond
      condition.

PMID- 21194584
TI  - In vitro evaluation of color replication of metal ceramic specimens using visual
      and instrumental color determinations.
AB  - STATEMENT OF PROBLEM: It remains unclear whether or not the performance of
      intraoral colorimetric devices is accurate. PURPOSE: The purpose of this study
      was to evaluate the color replication of metal ceramics using an intraoral
      colorimeter and visual shade determination. MATERIAL AND METHODS: Twenty-five
      metal ceramic specimens were prepared to match 5 different shades (A1, B1, C3,
      D3, A3.5) of the Vitapan Classical shade guide. Five clinicians determined the
      shades of the specimens using the same shade guide. The shade determination was
      based on the agreement of at least 3 of the 5 observers. Instrumental shade
      determinations were made with an intraoral colorimeter (ShadeEye NCC) to obtain
      results in terms of the Vitapan Classical shade guide. Based on these shade
      determinations, 50 additional metal ceramic specimens (25 visually determined and
      25 instrumentally determined) were prepared. The master (initial) and definitive
      (additional) specimens were analyzed with a spectrophotometer. L*, a*, b* values
      of each specimen were measured, and the color difference between the master and
      definitive specimens was calculated. The Wilcoxon signed rank test was used to
      analyze the color difference (DeltaE) values (alpha=.05). RESULTS: Visual shade
      determination produced lower DeltaE values than instrumental shade determination.
      The differences between DeltaE values of different shade determination methods
      were significant for master specimens of the shades B1 and A3.5 (P=.02). The
      DeltaE value calculated from the result of instrumental determination of shade B1
      (DeltaE=2.97) was within the clinically acceptable limit (DeltaE=3.5), whereas
      the DeltaE value for A3.5 (4.03) exceeded the limit for clinical acceptability.
      The DeltaE values for C3 exceeded the acceptable limit for both shade
      determination methods (DeltaE>3.5). CONCLUSIONS: Color replication of metal
      ceramic specimens using visual shade determination was more accurate compared to
      instrumental shade determination. The replication of the high-value shades (A1
      B1) was observed to be reliable with both shade determination methods.

PMID- 21194585
TI  - Effects of soldering and laser welding on bond strength of ceramic to metal.
AB  - STATEMENT OF PROBLEM: Welding or soldering of metal frameworks negatively affects
      the overall bond strength between the veneering ceramic and metal. PURPOSE: The
      purpose of this study was to evaluate the effect of soldering and laser-welding
      procedures on the bond strength between ceramic and metal. MATERIAL AND METHODS:
      Thirty Ni-based metal specimens (Wiron 99) (8 * 4 * 4 mm) were fabricated and
      divided into 3 groups; soldered (S), laser welded (L), and control (untreated
      cast alloy) (n=10). In S and L specimens, a notch (1 * 1.5 mm) was prepared
      longitudinally on the surface of each specimen and filled with compatible alloy
      (Wiron soldering rods and Wiroweld NC, respectively). Vickers hardness
      measurements were made after polishing the surfaces with a metallographic
      polishing kit. A veneering ceramic (VITA VMK 95) was vibrated, condensed in a
      mold, and fired on the metal frameworks. The specimens were sectioned in 2 axes
      to obtain nontrimmed bar specimens with a bonding area of approximately 1 mm2.
      Forty bars per block were obtained. Each bar was subjected to microtensile bond
      strength (MUTBS) testing with a crosshead speed of 1 mm/min. The MUTBS data (MPa)
      were recorded, and SEM was used for failure analysis of the tested bars. The
      measurements were statistically analyzed using a 1-way ANOVA and Tamhane tests
      (alpha=.05). RESULTS: The mean differences in MUTBS of veneering ceramic to
      soldered (10.4 +/-2.4 MPa) and laser-welded (11.7 +/-1.3 MPa) metal surfaces were
      not significantly different and were significantly lower than that of the cast
      alloy (25.4 +/-3.6 MPa) (P<.05). The mean Vickers hardness of cast alloy was
      significantly higher (236 +/-17 HV) than soldered (114 +/-9 HV) and laser-welded
      groups (129 +/-11 HV) (P<.05). CONCLUSIONS: Soldering and laser welding
      significantly decreased the MUTBS of a veneering ceramic to a base metal alloy.

PMID- 21194586
TI  - Corrosion of CoCr and NiCr dental alloys alloyed with palladium.
AB  - STATEMENT OF PROBLEM: A new subclass of casting alloy composition involving the
      addition of palladium (25 wt%) to traditional base metal alloys, thereby raising
      their classification to that of a noble alloy, has been recently introduced.
      Little is known about this class of casting alloy, particularly its corrosion
      properties, which influence its biocompatibility and esthetics. PURPOSE: The
      purpose of this study was to evaluate the corrosion properties of 2 new CoPdCr
      and one new NiPdCr alloy and compare them to traditional CoCr and NiCr alloys.
      MATERIAL AND METHODS: The casting alloys investigated were: CoPdCr-A (NobleCrown
      NF), CoPdCr-I (Callisto CP+), NiPdCr (Noble Crown), CoCr (Argeloy N.P. Special),
      and NiCr (Argeloy N.P. Star). Cylindrical (4.8-mm diameter) as-cast and oxidized
      specimens were assessed electrochemically in phosphate-buffered saline at 24
      degrees C (n=8 and n=6, respectively). The open circuit potential (OCP) was
      monitored for 20 hours, followed by linear polarization and cyclic polarization
      tests. A generalized linear mixed model was used to determine whether differences
      existed between alloys and to examine the effect of oxidation (alpha=.05).
      Representative alloy surfaces were scanned and examined with light microscopy.
      RESULTS: The palladium-containing alloys possessed a significantly greater OCP
      (P<.001); however, their polarization resistance was less and the corrosion
      current density was significantly greater (P<.05) than their traditional CoCr and
      NiCr alloy counterparts. Additionally, a greater incidence of pitting was
      observed in the palladium-containing alloys. Some differences were noted within
      alloys between the as-cast and oxidized conditions, but a major trend was not
      observed. CONCLUSIONS: Overall, the inclusion of palladium in CoCr and NiCr
      alloys had deleterious effects on electrochemical corrosion properties.

PMID- 21194587
TI  - Relationship of denture cast measurements to width of maxillary anterior teeth.
AB  - STATEMENT OF PROBLEM: When making complete dentures, clinicians may have
      difficulty with selection of properly sized denture teeth. PURPOSE: The purpose
      of this study was to determine if there are specific measurements made on an
      edentulous cast that could be useful to clinicians for selection of proper
      maxillary anterior denture tooth width. MATERIAL AND METHODS: Following
      Institutional Review Board approval, measurements were made on 50 maxillary and
      mandibular sets of complete denture casts and their marked and contoured
      occlusion rims and record bases consecutively submitted to a dental laboratory.
      The following 6 measurements were recorded for each set of casts: left mid
      maxillary to right mid-maxillary, representing the distance between the
      respective residual ridge crest points adjacent to each canine eminence; left
      retromolar pad to right retromolar pad; incisive papilla to left hamular notch;
      incisive papilla to right hamular notch; left hamular notch to right hamular
      notch; and incisive papilla to vibrating line. These measurements were
      statistically compared with the control, the canine-to-canine distance as marked
      on the contoured maxillary occlusion rim to indicate the relaxed commissures. The
      casts were also classified as small, medium or large based upon the tooth width
      specified by the commercial mold guide for their respective canine-to-canine
      control measurement. The estimation bias was determined for each of the 6
      measurements, and for those measurements for which the bias was significantly
      different from zero, a bias-correction was applied. St. Laurent's coefficient was
      used to describe the agreement between each (bias-corrected) measurement and the
      canine-to-canine control. A commercial guide was used to determine the accuracy
      of each of the 6 bias-corrected measurements in classifying denture teeth width
      as small, medium or large as compared to the same classification using the canine
      to-canine control. RESULTS: The bias-corrected measurement from the left hamular
      notch mark to the right hamular notch mark, obtained by adding 10 mm, exhibited
      the greatest degree of agreement with the control. This measurement was also the
      only one of the 6 that correctly classified more than 50% of both the medium and
      large casts. None of the 6 measurements classified more than 30% of the small
      casts correctly. CONCLUSIONS: Of the 6 measurements considered here, the bias
      corrected measurement from left hamular notch mark to right hamular notch mark
      was preferred for selecting denture teeth width.

PMID- 21194588
TI  - Efficacy of denture cleansers on Candida spp. biofilm formed on polyamide and
      polymethyl methacrylate resins.
AB  - STATEMENT OF PROBLEM: Although new materials have emerged as options to fabricate
      removable dental prostheses, the development of Candida biofilms on these
      materials and the effectiveness of methods to control these pathogenic biofilms
      are poorly understood. PURPOSE: The purpose of this study was to evaluate the
      efficacy of denture cleansers on Candida single- and dual-species biofilms formed
      on polyamide resin. MATERIAL AND METHODS: Polymethyl methacrylate (PMMA) resin
      (Acron MC) and polyamide resin (Flexite M.P.) specimens (n=116) were prepared,
      and their surface roughness was standardized (0.34 +/-0.02 MUm). Surface free
      energy (SFE) was measured for some specimens (n=20 per resin), while the
      remainder were randomly divided by lottery into 24 groups (n=8) for biofilm
      assay. C. albicans and/or C. glabrata biofilm was formed for 72 hours, and then
      specimens were treated with an enzymatic cleanser solution (Polident 3 Minutes),
      a cleanser solution (Corega Tabs), or 0.5% sodium hypochlorite (NaOCl) solution.
      Water served as the negative control. Remaining adherent microorganisms were
      removed from the treated specimens by ultrasonic waves, and colony-forming units
      (CFU) of each microorganism were calculated. SFE data were analyzed by 1-way
      ANOVA, and Candida species data were analyzed by 3-way ANOVA followed by the
      Tukey-Kramer test (P=.05). RESULTS: All tested biofilms displayed significantly
      higher growth on polyamide resin (P<.001), which presented the lowest SFE.
      Denture cleansers significantly decreased Candida levels; however, the 0.5% NaOCl
      solution was the only effective cleanser. C. glabrata revealed significantly
      higher CFU counts under all experimental conditions (P<.001). CONCLUSIONS: The
      highest Candida spp. biofilm growth was shown to occur on polyamide resin when
      compared with PMMA. Denture cleansers were able to remove Candida spp. biofilm
      formed on both denture base resins.

PMID- 21194589
TI  - Impression technique for ovate pontics.

PMID- 21194590
TI  - A method for removing calculus accumulated at the interface between implant
      abutments and the overlying bar.

PMID- 21194591
TI  - Golimumab: Review of the efficacy and tolerability of a recently approved tumor
      necrosis factor-alpha inhibitor.
AB  - BACKGROUND: Golimumab (GLM) is a tumor necrosis factor-alpha (TNF-alpha)
      inhibitor that was approved in the United States in 2009 for use with
      methotrexate (MTX) in adults with moderate to severe active rheumatoid arthritis
      (RA), and with or without MTX or other non-biologic disease-modifying
      antirheumatic drugs in adults with active psoriatic arthritis (PsA) or active
      ankylosing spondylitis (AS). GLM is administered as a 50-mg subcutaneous
      injection once a month. OBJECTIVES: The goals of this article were to review the
      current literature on GLM and to provide recommendations for the use of GLM based
      on the published information. METHODS: The PubMed, Cochrane Central Register of
      Controlled Trials, ClinicalTrials.gov, International Pharmaceutical Abstracts,
      and other databases, as well as the Web sites for the American College of
      Rheumatology (ACR) and the European Union League Against Rheumatism, were
      searched for relevant articles published in English between the inception of the
      databases through April 2010. Search terms included golimumab and CNTO 148.
      Pharmacologic, pharmacokinetic, clinical, outcomes, and economic studies as well
      as meta-analyses, case reports, and select abstracts were eligible for inclusion.
      Review articles on GLM were not used except to identify other primary papers.
      RESULTS: Seven clinical studies were identified and used to evaluate the efficacy
      and tolerability of GLM: 5 in patients with RA (4 subcutaneous administration and
      1 intravenous administration), 1 in patients with PsA (subcutaneous), and 1 in
      patients with AS (subcutaneous). In MTX-naive patients with RA, the number of
      patients satisfying the ACR20 response criteria (>20% improvement in ACR response
      rate) at 24 weeks was significantly higher for the GLM + MTX groups than for the
      MTX-only groups (62% vs 49%, respectively; P < 0.05). In patients with active RA
      despite MTX therapy, ACR20 responses at 14 to 16 weeks were significantly higher
      for the combined GLM + MTX groups than for the MTX groups (50%-79% vs 33%-37%,
      respectively; P < 0.001). GLM was more effective than placebo, both with and
      without MTX, in patients with RA and a history of treatment with 1 or 2 TNF-alpha
      inhibitors (ACR20 at 14 weeks, 35%-37% vs 18%, respectively; P < 0.001). Studies
      of other TNF-alpha inhibitors reported ACR20 responses in 53% to 59% of patients
      with active RA at 24 weeks. GLM was also more effective than placebo at 24 weeks
      in patients with PsA (ACR20, 52%-61% vs 12%, respectively; P < 0.001) (ASAS40
      [40% improvement based on Assessment in Ankylosing Spondylitis International
      Working Group criteria], 44%-54% vs 15%, respectively; P < 0.001). Studies of
      other TNF-alpha inhibitors reported ACR20 responses at 24 weeks in 55% to 57% of
      patients with PsA and ASAS40 responses in 46% to 47% of patients with AS. The
      incidence of any adverse effect appeared to be comparable in the GLM (61.2%
      93.9%) and placebo groups (59.3%-85.3%), but withdrawals because of adverse
      effects were higher in the GLM groups (0%-12.1%) than in the placebo groups (0%
      5.9%). The incidence of serious infections was comparable for GLM (0%-4.4%) and
      placebo (0.8%-3.5%). The most frequently reported adverse effects in the GLM
      groups were injection-site reactions (2.7%-37.1%), nausea (2.7%-22.9%), headache
      (3.8%-21.2%), nasopharyngitis (1.9%-15.0%), and upper respiratory tract
      infections (5.7%-13.8%). CONCLUSIONS: Based on the results of the studies
      included in this review, GLM appeared to be more effective than placebo in
      patients with RA, PsA, or AS. Clinical studies have not directly compared GLM
      with other TNF-alpha inhibitors. However, according to the available efficacy and
      tolerability data, GLM should be considered as the first or second TNF-alpha
      inhibitor for the treatment of PsA or AS and as the second or possibly first TNF
      alpha inhibitor in combination with MTX for the treatment of RA.

PMID- 21194592
TI  - Challenges and opportunities in establishing scientific and regulatory standards
      for determining therapeutic equivalence of modified-release products: Workshop
      summary report.
AB  - BACKGROUND: Modified-release (MR) products are complex dosage forms designed to
      release drug in a controlled manner to achieve the desired efficacy and safety
      profiles. Inappropriate control of drug release from such products may result in
      reduced efficacy or increased toxicity. OBJECTIVE: This paper is a summary report
      of the American Association of Pharmaceutical Scientists, International
      Pharmaceutical Federation, and Product Quality Research Institute workshop titled
      "Challenges and Opportunities in Establishing Scientific and Regulatory Standards
      for Assuring Therapeutic Equivalence of Modified Release Products", held October
      1-2, 2009, in Baltimore, Maryland. METHODS: The workshop provided an opportunity
      for pharmaceutical scientists from academia, industry, and regulatory agencies to
      discuss current regulatory expectations and industry practices for evaluating the
      pharmaceutical equivalence and bioequivalence of oral MR products. RESULTS: In
      the case of conventional monophasic MR formulations, the current regulatory
      approaches and criteria for bioequivalence evaluation were considered adequate
      for the assessment of therapeutic equivalence and inter-changeability of drug
      products. Additional measures may occasionally be needed to determine the
      bioequivalence of multiphasic MR products. The metric of partial AUC proposed by
      the US Food and Drug Administration received broad support as an additional
      measure for evaluating bioequivalence of multiphasic MR products designed to have
      a rapid onset of drug action followed by sustained response. The cutoff for
      partial AUCs may be based on the pharmacokinetic/pharmacodynamic or
      pharmacokinetic/ response characteristics of the products under examination. If
      the new metric is highly variable, the bioequivalence limits may be set based on
      the known within-subject variability for the reference product. CONCLUSIONS: The
      current regulatory approaches and criteria for bioequivalence evaluation were
      considered adequate for the assessment of therapeutic equivalence and
      interchangeability of conventional monophasic MR products. Additional measures
      may occasionally be needed to establish the bioequivalence of multiphasic MR
      products, and development of such measures is an important objective. The metric
      of partial AUC was proposed for products designed to have a rapid drug action
      followed by sustained response.

PMID- 21194593
TI  - Comparison of outcomes from daptomycin or linezolid treatment for vancomycin
      resistant enterococcal bloodstream infection: A retrospective, multicenter,
      cohort study.
AB  - BACKGROUND: The optimal treatment for bloodstream infections (BSIs) with
      vancomycin-resistant enterococci (VRE) is unknown. OBJECTIVE: This study examined
      outcomes in patients treated with daptomycin or linezolid for VRE BSI. METHODS: A
      retrospective, multicenter, cohort study was performed via chart review.
      Hospitalized patients treated for VRE BSI with daptomycin or linezolid from
      September 1, 2003, to June 30, 2007, were identified via pharmacy and
      microbiology reports at each institution. Patients aged <18 years or with
      polymicrobial bacteremia were excluded from analysis. Linezolid and daptomycin
      were included because the participating institutions used either of the 2 agents
      as first-line treatment for VRE BSI. Univariate and multivariate analyses were
      performed to determine the effect of drug selection on mortality and duration of
      BSI. Duration of BSI was defined as the amount of time from the draw date of the
      first positive blood culture to the draw date of the first finalized negative
      blood culture. Adverse events were not assessed. RESULTS: One-hundred one
      patients from 3 participating US hospitals experiencing VRE BSI were identified.
      Sixty-seven patients were treated with daptomycin and 34 with linezolid. Baseline
      characteristics appeared comparable between the daptomycin- and linezolidtreated
      groups, with the exception of shock (P = 0.049), prior vancomycin treatment (P =
      0.002), and prior linezolid treatment (P < 0.001), all of which occurred
      significantly more often in daptomycin-treated patients. Inpatient mortality
      occurred in 31 daptomycin- and 10 linezolid-treated patients (46.3% vs 29.4%; P =
      NS). Linear regression found that shock (P = 0.015), infective endocarditis (P =
      0.021), and concurrent rifampin or gentamicin treatment (P = 0.01) were
      associated with prolonged duration of positive cultures. Logistic regression
      revealed that shock (odds ratio [OR] = 14.24; P = 0.008), infection with
      Enterococcus faecium (OR = 53.10; P = 0.024), previous linezolid treatment (OR =
      6.63; P = 0.031), concurrent rifampin or gentamicin treatment (OR = 6.48; P =
      0.046), and a nonline source of infection (OR = 6.67; P = 0.019) were associated
      with increased mortality. CONCLUSIONS: In this retrospective cohort analysis,
      there were no significant differences in mortality of VRE BSI between patients
      receiving daptomycin or linezolid. Underlying comorbidities appeared to best
      predict outcome; however, given the retrospective nature of this study, larger,
      prospective, randomized, comparative studies are needed to control for potential
      biases and determine definitive outcome differences between these 2
      antimicrobials.

PMID- 21194594
TI  - Impact of 6 weeks of treatment with low-dose metformin and atorvastatin on
      glucose-induced changes of endothelial function in adults with newly diagnosed
      type 2 diabetes mellitus: A single-blind study.
AB  - BACKGROUND: Statin treatment has been reported to improve survival in patients
      with atherosclerosis, partly by improving vascular endothelial function.
      Elevation of blood glucose concentrations impairs endothelial function and
      promotes atherogenesis, but the effect of statins on glucose-induced endothelial
      dysfunction is unknown. Endothelium-dependent dilation (EDD) measured by gauge
      strain plethysmography in the forearm is considered to be a reliable marker of
      endothelial function in forearm resistance vessels. OBJECTIVE: This study
      examined the combined effects of metformin and atorvastatin treatment on glucose
      induced endothelial dysfunction (as EDD) in patients with newly diagnosed type 2
      diabetes mellitus (DM). METHODS: Patients with newly diagnosed DM were recruited
      and were randomly assigned to receive metformin 850 mg/d or metformin 850 mg/d +
      atorvastatin 10 mg/d for 6 weeks in a single-blind study. All patients underwent
      glucose loading (75 g oral glucose after 12 hours of fasting) at baseline and at
      the end of the treatment period. Blood samples were obtained at baseline before
      glucose loading and 3 hours after loading to determine serum concentrations of
      cholesterol, lipoproteins, triglycerides, glucose, and glycosylated hemoglobin.
      EDD was evaluated at baseline and at 1, 2, and 3 hours after loading. The
      investigators were blinded to the treatment group assignments, and all analyses
      were performed in a blinded manner. Adverse events (eg, gastrointestinal
      disorders, myopathy, liver disorders) were monitored based on reported symptoms
      or signs (eg, myalgias, muscle cramps), clinical examination, and laboratory
      parameters (eg, increased liver and muscle enzymes). RESULTS: Thirty-two white
      patients with newly diagnosed type 2 DM were randomly assigned to receive
      metformin 850 mg/d (n = 17 [12 men]; mean [SD] age, 53.88 [45] years; body mass
      index [BMI], 28.7 [4.5] kg/m2) or metformin 850 mg/d + atorvastatin 10 mg/d (n =
      15 [6 men]; mean age, 52.53 [37] years; BMI, 28.5 [2.1] kg/m2). At baseline, EDD
      was reduced 1 and 2 hours after glucose loading in both study groups (P < 0.01).
      Glucose loading was associated with an elevation of blood glucose concentrations
      at 1 and 2 hours (P < 0.01 vs resting levels before loading), and concentrations
      returned to resting levels at 3 hours, in both groups at baseline and after
      treatment. Metformin alone or in combination with atorvastatin was associated
      with a significant reduction in resting glucose concentrations after 6 weeks
      (both, P < 0.05 vs baseline), but only the combination of metformin +
      atorvastatin partly prevented the glucose-induced elevation of serum glucose at 1
      hour after loading and the glucose-induced decrease in EDD (both, P < 0.01 vs
      baseline). CONCLUSIONS: Glucose loading blunted endothelial function, with a
      deterioration in EDD, in these patients with newly diagnosed type 2 DM. However,
      combined treatment with metformin and atorvastatin for 6 weeks partly prevented
      the glucose-induced impairment of EDD in these patients, with a significant
      difference compared with monotherapy with metformin.

PMID- 21194595
TI  - Allergic shock and death associated with protamine administration in a diabetic
      patient.
AB  - BACKGROUND: Insulin is used to treat patients with both type 1 and type 2
      diabetes mellitus. Allergic reactions to insulin might be triggered by insulin
      itself or inactive ingredients in the insulin formulation, including proteins
      such as protamine in neutral protamine Hagedorn (NPH) insulin. The use of highly
      purified animal insulin and human recombinant insulin has reduced the incidence
      of anaphylactic reactions to insulin from ~30% to <1%. OBJECTIVE: We report a
      case of fatal allergic shock after the administration of protamine in a patient
      with a history of allergy to fish and a protamine-containing insulin. CASE
      SUMMARY: A 72-year-old Chinese male patient (height, 175 cm; weight, 80 kg) with
      a history of diabetes and progressive limb weakness was diagnosed with spinal
      vascular malformations after admission to the Xuan Wu Hospital of Capital Medical
      University, Beijing, People's Republic of China. He underwent epidural spinal
      cord arteriovenous fistula embolization with a liquid embolic agent (ethylene
      vinyl alcohol copolymer) after spinal cord angiography. During the operation,
      heparin was infused every hour with 6250, 2500, 2500, and 1250 IU, respectively.
      The last dose of heparin was administered ~10 minutes before the operation was
      completed. This was followed by the administration of protamine to neutralize the
      remaining heparin in the patient's body. Blurry vision and dizziness 5 minutes
      after protamine administration were followed by pruritus and hives over his neck
      and face. Oxygen was administered and 10 mg of dexamethasone with 2 mg of
      epinephrine was injected. The patient's heart rate dropped, his blood pressure
      decreased, and his arterial oxygen saturation (SaO2) declined progressively.
      About 10 minutes after the administration of protamine sulfate, the patient
      developed bradycardic arrest. Cardiopulmonary resuscitation efforts were
      undertaken and the patient was administered epinephrine 2 mg IV, atropine 0.5 mg
      IV, and subsequently, intravenous dopamine (50 mg/h). Ten minutes later, the
      patient's heart rate gradually increased, but blood pressure fluctuated, and SaO2
      ranged from 90% to 100%. Despite the initial response, the patient lost
      consciousness and heart rate declined progressively within 5 hours. Vasoactive
      agents including dopamine, norepinephrine, and adrenaline were administered.
      After all these measures proved ineffectual, the patient died. It was later
      determined that the patient had a history of allergic reactions to fish as well
      as to a premixed insulin that contained soluble human insulin 30% and low-protein
      intensive insulin zinc 70% (NPH). The Naranjo adverse drug reaction probability
      scale score for the association of protamine with the allergic reaction was 4,
      suggesting a possible relationship. CONCLUSION: This case report highlights a
      preventable fatal allergic reaction possibly associated with protamine
      administration in a patient with a history of allergy to a protamine-containing
      insulin.

PMID- 21194596
TI  - Acute hepatitis associated with the use of levofloxacin.
AB  - BACKGROUND: Levofloxacin is a fluoroquinolone used globally to treat respiratory,
      skin, and genitourinary tract infections. It is generally well tolerated and
      there is a very low risk for liver injury in patients taking this antibiotic.
      OBJECTIVE: We report an acute case of hepatitis following treatment with
      levofloxacin for pneumonia. CASE SUMMARY: A 77-year-old white male (height, 162
      cm; weight, 58 kg) with chronic bronchitis presented to the emergency department
      of the Hospital Curry Cabral, Lisbon, Portugal, with respiratory difficulty and
      productive cough. The patient had a history of chronic bronchitis, arterial
      hypertension, hypercholesterolemia, and benign prostatic hyperplasia, and was
      being treated with salmeterol 50 MUg plus fluticasone 250 MUg BID, and amlodipine
      5 mg, simvastatin 20 mg, alfuzosin 10 mg, and finasteride 5 mg once daily.
      Initially, the patient refused admission and was sent home, medicated with
      levofloxacin 500 mg once daily (single dose) for pneumonia and acetaminophen 1 g
      (as needed, maximum TID) if axillary temperature exceeded 38.0 degrees C (100.4
      degrees F). Three days later, the patient returned for a follow-up visit, and
      despite clinical and radiologic improvement, blood tests revealed a slight
      aggravation of anemia. On the seventh day of treatment with levofloxacin, the
      patient showed an elevation of transaminases. The temporal relation between the
      use of levofloxacin and the liver injury, the exclusion of other causes of
      hepatitis, and a compatible liver biopsy (conducted 14 days after identification
      of hepatitis) was consistent with the diagnosis of levofloxacin-associated
      hepatotoxicity. Levofloxacin treatment was stopped and the patient made a full
      recovery. The Naranjo Adverse Drug Reaction Probability Scale score for this
      association was "probable" (score 7) and the Roussel Uclaf Causality Assessment
      Method Scale score was "highly probable" (score 9). Unlike the 5 reported cases
      in the literature, this is the only case in which both a liver biopsy was
      performed in the course of the disease and the patient survived. CONCLUSION: The
      acute hepatitis observed in this elderly patient was probably associated with the
      administration of levofloxacin.

PMID- 21194597
TI  - Efficacy and tolerability of enteral formulations of ibuprofen in the treatment
      of patent ductus arteriosus in preterm infants.
AB  - BACKGROUND: The persistence of a patent ductus arteriosus (PDA) in preterm
      infants complicates their clinical course and may contribute to increased
      morbidity. Intravenous preparations of ibuprofen constitute one of the standard
      therapies for closure of a PDA. However, the unavailability of intravenous
      ibuprofen in certain regions of the world and the availability of inexpensive
      oral preparations has led to off-label nasogastric administration of oral
      ibuprofen in preterm infants with PDA. OBJECTIVE: This article reviews and
      comments on the evidence for the enteral use of oral formulations of racemic
      ibuprofen for PDA closure in preterm infants, with a focus on the risk of
      necrotizing enterocolitis (NEC). METHODS: MEDLINE, Current Contents, and Google
      Scholar were searched in April 2010 for trials of enteral ibuprofen in the
      treatment of PDA in preterm or low-birth-weight infants using the terms
      treatment, pharmacokinetics, ibuprofen, oral, enteral, patent ductus arteriosus,
      PDA, preterm, premature, low birth weight, infant, and newborn. Relevant congress
      Web sites were also searched for relevant abstracts. RESULTS: The literature
      search identified 2 pharmacokinetic studies involving 32 infants and 13 clinical
      efficacy studies involving 306 infants treated with enteral ibuprofen. The
      clinical studies reported some benefit for enteral ibuprofen relative to the
      comparators. However, these studies had methodologic limitations, including small
      numbers of subjects, lack of blinding, inclusion of preterm infants with a higher
      gestational age, customized treatment regimens, and second-order statistical
      error that prevented conduct of a systematic review. When the results of all
      studies were pooled, NEC was reported in a total of 46 of 281 infants (16%)
      receiving enteral ibuprofen and 21 of 83 infants (25%) receiving indomethacin.
      This rate of NEC with enteral ibuprofen was twice that reported for intravenous
      ibuprofen in a recent meta-analysis (27/356 [8%]). CONCLUSIONS: The evidence
      supporting the off-label use of enteral ibuprofen for PDA in preterm infants is
      weak. Well-designed, appropriately powered pharmacologic and controlled clinical
      studies are needed before use of enteral ibuprofen can be recommended. In
      countries where an intravenous formulation of racemic ibuprofen is approved, off
      label use of enteral racemic ibuprofen cannot be supported.

PMID- 21194598
TI  - Sterile abscess formation in response to two separate branded long-acting
      gonadotropin-releasing hormone agonists.
AB  - BACKGROUND: Long-acting forms of gonadotropin-releasing hormone (GnRH) receptor
      agonists are commonly used for the treatment of central precocious puberty (CPP).
      Sterile abscess formation has been reported as a complication of leuprolide
      acetate, but not histrelin acetate. OBJECTIVE: The aim of this study was to
      report an adverse drug reaction in a child with sterile abscess formation
      following treatment with 2 different branded long-acting forms of GnRH agonists.
      CASE SUMMARY: An otherwise healthy 8-year-old white female (weight, 40.7 kg;
      height, 140.1 cm) with documented CPP and no known drug allergies developed a
      sterile abscess at the site of the monthly intramuscular injection of 15 mg of
      leuprolide acetate. Because of this site reaction, a 50-mg histrelin acetate
      insert was placed in the patient's left arm. A similar reaction occurred 2 weeks
      after insert placement on 2 separate occasions in different arms. At the time of
      the removal of the second insert, Gram stain and swab culture of the purulent
      wound discharge were negative. The child was subsequently treated with intranasal
      nafarelin (800 ug twice daily) and tolerated it well. The Naranjo Adverse Drug
      Reaction Causality Score was 10 (definite, >=9). CONCLUSION: This report
      describes a case of sterile abscess formation definitely associated with 2
      different forms of long-acting GnRH agonist treatment in a child.

PMID- 21194599
TI  - Systematic reviews: When the published literature is the data.

PMID- 21194600
TI  - Results of a model analysis of the cost-effectiveness of liraglutide versus
      exenatide added to metformin, glimepiride, or both for the treatment of type 2
      diabetes in the United States.
AB  - BACKGROUND: Nearly half of all US patients with type 2 diabetes mellitus (T2DM)
      are unable to maintain adequate glycosylated hemoglobin (HbA1(c)) control (ie,
      <7.0%). OBJECTIVE: The aim of this work was to determine the long-term cost
      effectiveness of incretin-based therapy with once-daily liraglutide (vs twice
      daily exenatide) combined with metformin, glimepiride, or both for the treatment
      of T2DM. METHODS: Patient data were obtained from the Liraglutide Effect and
      Action in Diabetes 6 (LEAD 6) trial. Baseline data included mean HbA1(c) (8.15%),
      age (56.7 years), disease duration (8 years), sex, body mass index, blood
      pressure, lipid levels, cardiovascular and renal risk factors, and other
      complications. The IMS Center for Outcomes Research Diabetes Model was used to
      project and compare lifetime (ie, 35-year) clinical and economic outcomes for
      once-daily liraglutide 1.8 mg compared with twice-daily exenatide 10 (ig, each
      used as add-on therapy with maximum-dose metformin and/or glimepiride. Treatment
      effect assumptions were also derived from the LEAD 6 trial. Transition
      probabilities, utilities, and complication costs were obtained from published
      sources. All outcomes were discounted at 3% per annum, and the analysis was
      conducted from the perspective of a third-party payer in the United States.
      RESULTS: The base-case analysis indicated that, compared with exenatide,
      liraglutide add-on therapy was associated with a mean (SD) increase in life
      expectancy of 0.187 (0.250) years and an increase in qualityadjusted life-years
      of 0.322 (0.164) years. Compared with exenatide, total lifetime treatment costs
      for liraglutide were $12,956 higher, yielding an incremental costeffectiveness
      ratio (ICER) of $40,282. However, the costs of diabetes-related complications
      were lower with liraglutide than with exenatide ($49,784 vs $52,429,
      respectively). Sensitivity analysis indicated that setting patient HbA(1c) levels
      at the 95% upper limit reduced the ICER for liraglutide compared with exenatide
      to $33,086. CONCLUSION: In this model analysis using published clinical data and
      current medication acquisition price assumptions, liraglutide (in combination
      with metformin and/or glimepiride) appeared to be cost-effective in the US payer
      setting over a 35-year time horizon.

PMID- 21194601
TI  - Cost-effectiveness analysis of tapentadol immediate release for the treatment of
      acute pain.
AB  - BACKGROUND: Tapentadol immediate-release (IR) tablets are indicated for the
      treatment of moderate to severe acute pain. In clinical trials, tapentadol IR
      effectively reduced moderate to severe pain with improved tolerability compared
      with oxycodone IR at doses providing comparable analgesia. OBJECTIVE: This
      analysis compared the cost-effectiveness of tapentadol IR with doses of oxycodone
      IR providing comparable analgesia in the outpatient treatment of acute
      postsurgical and nonsurgical pain. The perspective was that of a US managed care
      health plan as third-party payer. METHODS: A Markov model was developed to
      simulate clinical-economic outcomes for tapentadol IR 100 mg compared with
      oxycodone IR 15 mg in the treatment of acute postsurgical pain (3 days) and for
      tapentadol IR 50 mg compared with oxycodone IR 10 mg in the treatment of acute
      nonsurgical pain (10 days). The model simulated changes in pain relief;
      occurrence of opioid-related adverse events (AEs); opioid switching,
      discontinuation, and dose change; and number of quality-adjusted life-days
      (QALDs). Data inputs for the model were obtained from clinical trials, claims
      databases, surveys, Medicare fee schedules, and other published sources. Only
      direct costs were included. Drug costs were based on the wholesale acquisition
      cost. Prescription copayments were set at $5 for oxycodone IR and $25 for
      tapentadol IR. All costs were in 2008 US dollars. Sensitivity analyses were
      conducted on key model parameters. RESULTS: The cost of pain medication per
      patient was higher for tapentadol IR than for oxycodone IR in both the surgical
      pain setting ($15.23 vs $9.57, respectively) and the nonsurgical pain setting
      ($57.17 vs $21.31). However, this cost difference was offset by reductions in
      pharmacy and medical costs associated with the treatment of AEs and opioid
      switching/discontinuation, resulting in a lower mean treatment cost per patient
      for tapentadol IR 100 mg compared with oxycodone IR 15 mg in the treatment of
      acute surgical pain ($52.90 vs $55.99) and for tapentadol IR 50 mg compared with
      oxycodone IR 10 mg in the treatment of acute nonsurgical pain ($139.48 vs
      $144.79). Tapentadol IR also was associated with a greater mean number of
      treatment days with >=30% improvement in pain intensity without opioid-related
      AEs compared with oxycodone IR and a greater mean number of QALDs (surgical pain:
      1.73 vs 1.68; nonsurgical pain: 6.03 vs 4.92). Because both doses of tapentadol
      IR were dominant (ie, lower treatment costs and greater effectiveness) relative
      to the corresponding doses of oxycodone IR providing com- parable analgesia,
      incremental cost-effectiveness ratios were not calculated. CONCLUSION: The
      results of this model suggest that at doses providing comparable analgesia,
      tapentadol IR is a cost-effective alternative to oxycodone IR for the treatment
      of acute surgical and nonsurgical pain.

PMID- 21194602
TI  - Comparative resource utilization in medicaid-eligible patients with asthma
      treated with fixed-dose fluticasone propionate/salmeterol or fluticasone
      propionate monotherapy.
AB  - OBJECTIVE: The aim of this work was to compare rates of asthma-related health
      service utilization for Medicaid-eligible pediatric and adult patients with
      asthma treated with fixed-dose fluticasone propionate/salmeterol (FSC) or
      fluticasone propionate (FP) monotherapy. METHODS: A retrospective, observational
      claims analysis was conducted with Medicaid enrollees aged >=4 years with >=1
      diagnosis code for asthma and a prescription fill for FSC or FP between January
      1, 2002, and November 1, 2005. The end date allowed a follow-up period of >=60
      days; Medicaid data were available through December 31, 2005, and were obtained
      from 2 sources: a large US-managed Medicaid provider affiliated with i3 Innovus,
      and the Thomson Medstat Marketscan (Ann Arbor, Michigan) Medicaid claims
      database. Patients were new or continuing users of asthma controllers, but were
      new users of FSC or FP. Outcome measures included postindex use of systemic
      corticosteroid drugs and short-acting beta-agonists (SABAs), asthma-related
      utilization, and costs. Descriptive and multivariate techniques were used,
      adjusting for differences in baseline demographics and length of follow-up time
      in the study population. Patients were grouped into cohorts according to age: 4
      to 17 or >=18 years. RESULTS: The final study population was 50,428 patients,
      including 30,071 patients (59.6%) aged <18 years and 20,357 patients (40.4%) aged
      >=18 years. Mean number of days of follow-up was 290.4, and 55.1% of patients (n
      = 27,793) were followed for >=1 year after the index date. Among those aged <18
      years, FSC treatment was associated with decreased adjusted risk of asthma
      related emergency department (ED) visits (adjusted hazard ratio [HR] = 0.917; 95%
      CI, 0.855-0.984) and combined ED/inpatient (IP) visits (HR = 0.922; 95% CI, 0.860
      0.988). Among those aged >=18 years, FSC treatment was associated with decreased
      adjusted risk of asthma-related ED visits (HR = 0.907; 95% CI, 0.849-0.969) and
      combined ED/IP visits (HR = 0.907; 95% CI, 0.850-0.968). FSC treatment was also
      associated with significantly fewer prescription fills for SABAs compared with FP
      treatment in both age groups (aged <18 years: incident rate ratio [IRR] = 0.960
      [95% CI, 0.929-0.992]; aged >=18 years: IRR = 0.950 [95% CI, 0.905-0.998]). Total
      mean (SD) unadjusted asthma costs were $579 ($2429) for FSC and $551 ($3151) for
      FP in the <18-year age group and were $1764 ($10,006) for FSC and $1512 ($5543)
      for FP in the >=18-year age group. CONCLUSION: In this retrospective database
      analysis, Medicaid-eligible patients who initiated FSC therapy experienced better
      asthma control compared with patients who initiated FP monotherapy, as measured
      by asthma-related ED/IP visits and use of SABAs.

PMID- 21194603
TI  - Perspectives on the bioequivalence and therapeutic equivalence of generic
      formulations: An overview of the landscape.

PMID- 21194604
TI  - Pharmacokinetics and safety of aclidinium bromide, a muscarinic antagonist, in
      adults with normal or impaired renal function: A phase I, open-label, single-dose
      clinical trial.
AB  - BACKGROUND: Aclidinium bromide is an inhaled, long-acting muscarinic antagonist
      currently in development for the treatment of chronic obstructive pulmonary
      disease. Renal impairment may affect drug clearance. OBJECTIVE: This study was
      conducted to evaluate the pharmacokinetic (PK) parameters, safety, and
      tolerability of aclidinium bromide and its metabolites in patients with normal
      and impaired renal function to determine whether dosing adjustments are required
      when renal dysfunction is present. METHODS: This was a Phase I, open-label,
      single-center, single-dose clinical trial conducted in Munich, Germany. Adults
      with varying degrees of renal function were assigned to 4 groups (n = 6 for each)
      based on creatinine clearance, including normal renal function (>80 mL/ min),
      mild renal insufficiency (>50-<=80 mL/min), moderate renal insufficiency (>30
      <=50 mL/min), and severe renal insufficiency (<30 mL/min). Single doses of
      aclidinium bromide 400 MUg were administered using a multidose dry powder
      inhaler. Blood and urine samples were obtained before dosing and at various time
      points up to 48 hours after dosing to analyze the PK parameters of aclidinium
      bromide and its metabolites. Plasma PK Parameters were AUC0-(t), MJC0-(infinity)
      C(max), T(max), t(1/2) CL/F and apparent volume of distribution during the
      terminal phase Xz; urinary parameters were the amount of aclidinium or acid or
      alcohol metabolite excreted in urine, the percentage of the dose excreted in
      urine (fe), and renal clearance (CL(R)). Tolerability was assessed using physical
      examination, vital signs, 12-lead ECG recordings, laboratory tests, and adverse
      event (AE) reports. The Wilcoxon rank sum test was used to compare the median PK
      values between the normal and impaired renal function groups. Pearson correlation
      coefficients and linear regression models were used to analyze the relationship
      between creatinine clearance and AUC0-(infinity) and between creatinine clearance
      and CL(R) for aclidinium and its metabolites. RESULTS: A total of 16 men and 8
      women were included in the study. All participants were white; mean (SD) age was
      55 (10.7) years and weight was 70.8 (9.2) kg. Aclidinium Cmax was observed in
      plasma by 5 minutes after dosing (ie, median Tmax) and did not differ
      significantly among the renal function groups. Plasma concentrations of
      aclidinium declined after reaching Cmax, with median t(1/2) values ranging from
      2.07 to 4.18 hours across all renal function groups. Most of the individual
      t(1/2) values were between 1.5 and 3.5 hours, regardless of the degree of renal
      insufficiency. No significant relationship between AUC0-(infinity)) and
      creatinine clearance was observed (Pearson correlation coefficient = -0.0446; P =
      NS). Urinary excretion of aclidinium was very low, with a mean 0.090% (median
      0.078%) of the dose recovered from the urine in participants with normal renal
      function. Eight AEs were reported in 7 participants after drug administration;
      all were mild to moderate in severity and resolved spontaneously. There were no
      serious drug-related AEs and no deaths. CONCLUSIONS: The plasma PK parameters of
      aclidinium bromide were not significantly altered after a single inhaled dose of
      aclidinium bromide 400 MUg in this small group of patients with various degrees
      of impaired renal function. The very low urinary excretion of aclidinium in all
      renal function groups indicates that renal function plays a minor role in
      aclidinium plasma clearance. Aclidinium appeared well tolerated in the population
      studied. These results suggest that aclidinium dose adjustment on the basis of
      renal function may not be necessary.

PMID- 21194605
TI  - Assessment of levetiracetam bioavailability from targeted sites in the human
      intestine using remotely activated capsules and gamma scintigraphy: Open-label,
      single-dose, randomized, four-way crossover study in healthy male volunteers.
AB  - BACKGROUND: Levetiracetam is a broad-spectrum antiepileptic drug that binds to
      synaptic vesicle protein SV2A. Levetiracetam is indicated in the adjunctive
      treatment of partial-onset seizures, myoclonic seizures, and generalized tonic
      clonic seizures. It is also approved in Europe as monotherapy for newly diagnosed
      partial-onset seizures. A Phase I clinical pharmacology trial was conducted
      during preregistration clinical development to better understand the regional
      gastrointestinal (GI) absorption of levetiracetam. OBJECTIVE: This study
      evaluated the relative bioavailability of levetiracetam in various regions of the
      GI tract using a noninvasive, remote-controlled capsule device providing targeted
      drug delivery, relative to that after oral administration, and explored the
      drug's absorption characteristics in healthy volunteers. METHODS: Pharmacokinetic
      data were obtained from healthy men aged 18 to 65 years in an open-label, single
      dose, randomized, 4-way crossover study. Treatments included levetiracetam 250 mg
      administered as an immediate-release tablet and capsule delivery of 250 mg drug
      substance (levetiracetam powder without excipients) to the proximal small bowel,
      distal small bowel, and ascending colon. The location of the capsule in the GI
      tract was monitored using gamma-scintigraphic imaging. Blood samples for plasma
      levetiracetam concentration were collected before dosing; at 10, 20, 30, and 45
      minutes; and at 1, 1.5, 2, 3, 6, 9, 12, 16, 20, and 24 hours after tablet intake
      or after capsule activation. Pharmacokinetic parameters C(max), T(max), AUC0
      (last), AUC0-(infinity) and t(1/2) were calculated using noncompartmental
      methods. Tolerability was determined using clinical assessment, monitoring of
      vital signs, laboratory analysis, and interviews with the volunteers regarding
      adverse events. RESULTS: Nine healthy men, 7 whites and 2 Asians, were enrolled
      (mean [SD] age, 31 [14] years; weight, 77 [5] kg; height, 176 [6] cm). Six
      volunteers completed all 4 treatments. Seven adverse events (headache [3],
      lethargy [2], tachycardia [1], and contusion [1]) were reported in 5 volunteers,
      but only 2 (headache and lethargy) were judged by the investigator to be possibly
      drug related. The geometric mean (%CV) AUC(0-last) values of levetiracetam
      delivered in the proximal small bowel, distal small bowel, ascending colon, and
      stomach (oral tablet) were 58.2 (9.3%), 59.6 (8.9%), 51.5 (12.0%), and 59.0
      (7.4%) MUg . h/mL, respectively. Values for bioavailability in the proximal small
      bowel, distal small bowel, and ascending colon relative to the tablet were 98.5%
      (95% CI, 89.7%-108.2%), 100.8% (95% CI, 91.4%-111.1%), and 87.1% (95% CI, 77.9%
      97.5%). CONCLUSION: After delivery in the proximal small bowel, distal small
      bowel, or ascending colon, the systemic bioavailability of levetiracetam (AUC),
      but not C(max) and T(max), appeared comparable to that after oral administration
      and thus appeared site independent in this small group of healthy fasting men.

PMID- 21194606
TI  - A bioequivalence comparison of two formulations of rifampicin (300- vs 150-mg
      capsules): An open-label, randomized, two-treatment, two-way crossover study in
      healthy volunteers.
AB  - BACKGROUND: Rifampicin is a semisynthetic antibiotic derivative of rifamycin used
      worldwide for the treatment of various forms of tuberculosis. OBJECTIVE: The
      objective of this study was to compare, under fasting conditions in healthy
      volunteers, the rate and extent of absorption of a generic rifampicin capsule in
      oral dosage form versus the proprietary equivalent formulation for the purpose of
      registration approval of the test formulation. METHODS: This was an open-label,
      randomized, 2-treatment, 2-way crossover study with an 8-week washout period
      between the 2 study arms. Healthy volunteers received a 300-mg capsule of the
      test formulation (Idaman Pharma Manufacturing Sdn. Bhd.) or two 150-mg capsules
      of the reference formulation. Blood samples were collected predose and at 45
      minutes and 1.25, 1.5, 2, 2.25, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours
      postdose. Plasma concentrations of rifampicin and its metabolite, 25-desacetyl
      rifampicin, were analyzed using a validated HPLC method. The formulations were
      considered bioequivalent if the 90% CIs for C(max) and AUC were within the
      predetermined bioequivalence range (80%-125%, according to the guidelines of the
      US Food and Drug Administration, or 75%-133% for Cmax only, as set by the
      European Commission-European Medicines Agency and the National Pharmaceutical
      Control Bureau of Malaysia). Tolerability was assessed by verbally questioning
      subjects regarding their well-being and any feelings of discomfort. All events
      reported by the subjects (serious or mild) were recorded on adverse-event forms.
      RESULTS: Fourteen healthy subjects (10 males, 4 females) with a mean age of 22.6
      years (range, 20-28 years) and a mean body mass index of 22.2 kg/m2 (range, 18.3
      29.9 kg/m2) were enrolled in the study; all 14 completed the trial as outlined in
      the protocol. The mean values for C(max), T(max) , AUC0-24, and AUC0-(infinity))
      with the test formulation of rifampicin were 7.20 MUg/mL, 1.32 hours, 37.12
      MUg/mL . h, and 39.69 MUg/mL . h, respectively; for the reference formulation,
      the values were 7.65 MUg/mL, 1.71 hours, 38.92 MUg/mL . h, and 42.24 MUg/ mL . h.
      For 25-desacetyl rifampicin, the mean values for C(max), T(max), AUC0-24, and
      AUC0-(infinity)) with the test formulation were 0.63 MUg/mL, 3.45 hours, 4.92
      MUg/mL . h, and 6.27 MUg/mL . h; for the reference formulation, the values were
      0.7 MUg/mL, 3.27 hours, 5.23 MUg/mL . h, and 6.84 MUg/mL . h. For rifampicin, the
      90% CIs for the test formulation/reference formulation ratio for the logarithmic
      transformations of both C(max) and AUC0-(infinity)) were within the
      bioequivalence limit of 80% to 125% (80.9109.7 and 80.7-103.2, respectively). For
      25-desacetyl rifampicin, the 90% CI for the test formulation/reference
      formulation ratio for the logarithmic transformations of AUC0-24 (80.0-104.7) was
      within the bioequivalence limit of 80% to 125%. However, the 90% CI for C(max)
      (78.4-102.2) was outside this limit but still within the acceptance limit for
      Cmax when adhering to the bioequivalence range of 75% to 133%. No adverse events
      were reported during the study. CONCLUSIONS: This study found that the 300-mg
      test capsule and the 150-mg reference capsules of rifampicin met the regulatory
      criteria for assuming bioequivalence in these fasting healthy volunteers. Both
      formulations appeared to be well tolerated in the population studied.

PMID- 21194607
TI  - Pharmacokinetics and tolerability of intravenous cefotetan disodium for injection
      in healthy Chinese volunteers: A randomized, open-label, single- and multiple
      dose study.
AB  - BACKGROUND: Cefotetan disodium for injection is a semisynthetic cephamycin
      antibiotic that exerts its bactericidal effects by inhibition of cell-wall
      synthesis. Despite being widely used in the treatment of various infections,
      little information is available on the pharmacokinetic properties of cefotetan
      disodium in Chinese subjects. OBJECTIVES: This study evaluated the
      pharmacokinetics of single and multiple intravenous doses of a generic
      formulation of cefotetan disodium in healthy Chinese volunteers. The effect of
      sex on the pharmacokinetics of cefotetan disodium was evaluated as a secondary
      objective. METHODS: In this open-label, dose-escalating study, subjects were
      randomized to receive a single dose of cefotetan disodium 0.5, 1.0, or 2.0 g
      administered as a 1-hour intravenous infusion. Those allocated to the 1.0-g dose
      continued into the multiple-dose phase, in which they received 1.0 g BID for 7
      consecutive days. During the single-dose phase, blood samples were collected at
      regular intervals from 0 to 15 hours after drug administration and were analyzed
      using a validated HPLC method. During the multiple-dose phase, blood samples were
      obtained before drug administration on days 5, 6, and 7 to determine the C(min)
      at steady state; on day 7, blood samples were also collected from 0 to 15 hours
      after drug administration. Tolerability was assessed based on physical
      examinations, vital signs, laboratory tests (hematology, biochemistry, hepatic
      and renal function, and urinalysis), and subject interviews. RESULTS: Three
      groups, each consisting of 5 men and 5 women, were enrolled in the single-dose
      phase. The mean (SD) age of subjects was 23.2 (2.2) years (range, 19-30 years).
      Their mean weight was 57.0 (6.3) kg (range, 46.4-72.0 kg), and their mean height
      was 1.66 (0.08) m (range, 1.48-1.81 m). After intravenous administration of
      single doses of 0.5, 1.0, and 2.0 g, the cefotetan disodium C(max) was 35.01
      (6.98), 76.67 (10.52), and 154.33 (27.17) mg/L, respectively; the AUC0-15(h) was
      145.35 (18.36), 307.45 (33.07), and 746.09 (103.07) mg . h/L; the AUC0-(infinity)
      was 171.51 (20.61), 347.25 (44.20), and 843.84 (131.13) mg . h/L; the t(1/2) was
      5.80 (1.29), 4.91 (1.15), and 5.04 (1.26) hours; the CL was 2.96 (0.41), 2.92
      (0.39), and 2.42 (0.39) L/h; and the V(d) was 24.55 (5.19), 20.37 (3.66), and
      17.30 (3.52) L. After administration of multiple doses, the cefotetan disodium
      C(max,ss) was 80.53 (10.04) mg/L; the C(mix,ss) was 11.00 (4.04) mg/L; the
      AUC(ss) was 347.92 (50.04) mg . h/L; the steady-state plasma concentration was
      28.99 (4.17) mg/L; the t(1/2) was 6.24 (2.52) hours; the CL was 2.32 (0.64) L/h;
      and the Vd was 19.19 (4.58) L. No significant differences in pharmacokinetic
      parameters were noted by sex in the multiple-dose phase. Cefotetan disodium
      appeared to be well tolerated. CONCLUSIONS: In these healthy Chinese subjects,
      the cefotetan disodium AUC and C(max) increased in a dose-proportional manner,
      whereas the t(1/2) was independent of dose. The pharmacokinetic properties of
      cefotetan disodium were linear at doses of 0.5 to 2.0 g. After multiple doses,
      the pharmacokinetic parameters of cefotetan disodium were consistent with those
      after single doses. At the doses studied, cefotetan disodium appeared to be well
      tolerated in these healthy volunteers.

PMID- 21194608
TI  - Relative bioavailability and pharmacokinetic comparison of two 2-mg risperidone
      tablet formulations: A single dose, randomized-sequence, double-blind, 2-way
      crossover study in healthy male volunteers in Thailand.
AB  - BACKGROUND: Data regarding the pharmacokinetic properties of risperidone in the
      Thai population are limited. A new generic tablet formulation was recently
      developed, but bioequivalence research is necessary to obtain marketing
      authorization for it in Thailand. OBJECTIVE: The aim of this study was to
      evaluate and compare the pharmacokinetic properties of risperidone and its active
      metabolite, 9-hydroxyrisperidone (which reportedly contributes to the drug's
      pharmacodynamic effects), in a newly developed generic tablet formulation (test)
      and a branded formulation (reference) in healthy, fasting, male Thai volunteers.
      METHODS: A single-dose, randomized-sequence, double-blind, 2-way crossover design
      was used in this study. The study took place from October 21 through November 28,
      2007. After a >=10-hour overnight fast, volunteers were orally administered one 2
      mg risperidone tablet, either the test formulation (Condrug International
      Company, Ltd.) or the reference formulation-according to the randomization
      schedule-followed by a 14-day washout period and administration of the alternate
      formulation. Blood samples were collected over a period of 96 hours. Risperidone
      and 9-hydroxyrisperidone plasma concentrations were simultaneously determined
      using a validated HPLC/ion trap mass spectrometry method. The plasma
      concentration-time curves of the active moiety, risperidone, and 9
      hydroxyrisperidone were generated for each volunteer, from which the C(max),
      T(max), AUC0-(last), AUC0-(infinity), and t(1/2) were determined using
      noncompartmental analysis. The effects of formulation, period, sequence, and
      subject (within sequence) on pharmacokinetic parameters were analyzed using
      ANOVA. According to regulatory requirements set forth by Thailand, the
      Association of Southeast Asian Nations, and the US Food and Drug Administration,
      products meet the criteria for bioequivalence if the 90% CIs of the treatment
      ratios for C(max) and AUC are within the range of 0.80 to 1.25. Tolerability was
      assessed by patient interview, monitoring vital signs (ie, resting blood
      pressure, heart rate, body temperature), physical examination, and laboratory
      tests (ie, urinalysis, hematology, blood chemistry) before and after the study.
      RESULTS: A total of 22 Thai male volunteers (mean [SD] age, 28.18 [8.27] years
      [range, 20.62-44.19 years]; weight, 62.43 [4.76] kg [range, 55.03-76.02 kg]; and
      body mass index, 21.76 [2.07] kg/m2 [range, 18.9924.91 kg/m2]) completed the
      study. The mean (SD) relative bioavailabilities of test to reference formulations
      determined from AUC of the active moiety, risperidone, and 9-hydroxyrisperidone
      were 1.06 (0.18), 1.07 (0.29), and 1.04 (0.17), respectively. The ANOVA suggested
      no statistically significant effect of formulation, period, or sequence on the
      studied pharmacokinetic parameters of the active moiety, risperidone, or 9
      hydroxyrisperidone. The 90% CIs for the natural logarithm-transformed ratios of
      C(max), AUC0-(last), and AUC0-(infinity) were as follows: for active moiety, 0.94
      to 1.03, 0.98 to 1.11, and 0.98 to 1.10, respectively; for risperidone, 0.90 to
      1.10, 0.96 to 1.13, and 0.96 to 1.14, respectively; and for 9-hydroxyrisperidone,
      0.91 to 1.03, 0.97 to 1.10, and 0.96 to 1.09, respectively. All met the criteria
      for bioequivalence. The most commonly reported adverse events (AEs) were
      somnolence (100.0%), orthostatic hypotension (13.6%), headache (4.5%), and
      syncope (2.3%). AEs were mild and disappeared within 1 day. No volunteers
      withdrew from the study because of AEs. CONCLUSIONS: The single-dose
      pharmacokinetic data in this small, all-male, selected sample of fasting, healthy
      volunteers met Thailand's regulatory criteria for assuming bioequivalence of the
      tested generic and reference 2-mg risperidone tablets. Both formulations were
      well tolerated.

PMID- 21194609
TI  - Synthesis, DNA binding, photo-induced DNA cleavage, cytotoxicity and apoptosis
      studies of copper(II) complexes.
AB  - Two new Cu(II) complexes, [Cu(acac)(dpq)Cl] (1) and [Cu(acac)(dppz)Cl] (2) (acac
      = acetylacetonate, dpq = dipyrido[3,2-d:20,30-f]quinoxaline, dppz = dipyrido[3,2
      a:20,30-c] phenazine), have been synthesized and their DNA binding, photo-induced
      DNA cleavage activity and cell cytotoxicity are studied. The complexes show good
      binding propensity to calf thymus DNA in the order: 2(dppz) >1(dpq). Furthermore,
      two complexes exhibit efficient DNA cleavage activity on natural light or UV-A
      (365 nm) irradiation via a mechanistic pathway involving formation of singlet
      oxygen as the reactive species. The photo-induced DNA cleavage activity of the
      dppz complex 2 is found to be more efficient than its dpq analogue. In vitro
      study of the photocytotoxicity of two complexes on HeLa cells indicate that both
      of them have the potential to act as effective anticancer drugs, with IC(50)
      values of 5.25+/-0.83 MUM (1) and 4.40+/-0.52 MUM (2) in the natural light, and
      2.57+/-0.92 MUM (1) and 2.18+/-0.52 MUM (2) in UV-A light. In addition, to detect
      an apoptotic HeLa body, cells were stained with Hoechst 33342 dye.

PMID- 21194610
TI  - The molecular mechanism of mammalian NO-synthases: a story of electrons and
      protons.
AB  - Since its discovery, nitric oxide synthase (NOS), the enzyme responsible for NO
      biosynthesis in mammals, has been the subject of extensive investigations
      regarding its catalytic and molecular mechanisms. These studies reveal the high
      degree of sophistication of NOS functioning and regulation. However, the precise
      description of the NOS molecular mechanism and in particular of the oxygen
      activation chemistry is still lacking. The reaction intermediates implicated in
      NOS catalysis continue to elude identification and the current working paradigm
      is increasingly contested. Consequently, the last three years has seen the
      emergence of several competing models. All these models propose the same global
      reaction scheme consisting of two successive oxidation reactions but they diverge
      in the details of their reaction sequence. The major discrepancies concern the
      number, source and characteristics of proton and electron transfer processes. As
      a result each model proposes distinct reaction pathways with different implied
      oxidative species. This review aims to examine the different experimental
      evidence concerning NOS proton and electron transfer events and the role played
      by the substrates and cofactors in these processes. The resulting discussion
      should provide a comparative picture of all potential models for the NOS
      molecular mechanism.

PMID- 21194611
TI  - Toxicity of depleted uranium complexes is independent of p53 activity.
AB  - The p53 tumor suppressor protein is one of the key checkpoints in cellular
      response to a variety of stress mechanisms, including exposure to various toxic
      metal complexes. Previous studies have demonstrated that arsenic and chromium
      complexes are able to activate p53, but there is a dearth of data investigating
      whether uranium complexes exhibit similar effects. The use of depleted uranium
      (DU) has increased in recent years, raising concern about DU's potential
      carcinogenic effects. Previous studies have shown that uranyl acetate and uranyl
      nitrate are capable of inducing DNA strand breaks and potentially of inducing
      oxidative stress through free radical generation, two potential mechanisms for
      activation of p53. Based on these studies, we hypothesized that either uranyl
      acetate or uranyl nitrate could act as an activator of p53. We tested this
      hypothesis using a combination of cytotoxicity assays, p53 activity assays,
      western blotting and flow cytometry. All of our results demonstrate that there is
      not a p53-mediated response to either uranyl acetate or uranyl nitrate,
      demonstrating that any cellular response to uranium exposure likely occurs in a
      p53-independent fashion under the conditions studied.

PMID- 21194612
TI  - Studies on synthesis, characterization, and G-quadruplex binding of Ru(II)
      complexes containing two dppz ligands.
AB  - In this work, the interaction between the guanine-rich single-strand oligomer
      AG(3)(T(2)AG(3))(3) quadruplex and two Ru(II) complexes,
      [Ru(L(1))(dppz)(2)](PF(6))(4) (1) and [Ru(L(2))(dppz)(2)](PF(6))(4) (2) (L(1) =
      5,5'-di(1-(trimethylammonio)methyl)-2,2'-dipyridyl cation, L(2) = 5,5'-di(1
      (triethylammonio)methyl)-2,2'-dipyridyl cation, dppz = dipyrido[3,2-a:2',3'-c]
      phenazine), has been studied by UV-Visible, fluorescence, DNA melting, and
      circular dichroism in K(+) buffer. The two complexes after binding to G
      quadruplex have shown different DNA stability and fluorescence enhancement. The
      results show that both complexes can induce the stabilization of quadruplex DNA.
      DeltaT(m) values of complexes 1 and 2 at [Ru]/[DNA] ratio of 1:1 were 9.4 and
      7.0, respectively. Binding stoichiometry along with the quadruplex was
      investigated through a luminescence-based Job plot. The major inflection points
      for complexes 1 and 2 were 0.49 and 0.46, respectively. The data were consistent
      with the binding mode at a [quadruplex]/[complex] ratio of 1:1. In addition, the
      conformation of G-quadruplex was not changed by the complexes at the high ionic
      strength of K(+) buffer.

PMID- 21194613
TI  - Synthesis, spectroscopic study and anticancer activity of a water-soluble Nb(V)
      peroxo complex.
AB  - We synthesized, characterized and studied the anticancer properties of a new
      water-soluble peroxo niobium complex (K(3)[Nb(Asc)(O(2))(3)].4H(2)O (Asc =
      ascorbate anion C(6)H(6)O(6)(2-))), as well as that of ascorbic acid, in human
      leukemic cells. The complex was synthesized and characterized by elemental, IR,
      Raman, thermogravimetric analysis, detailed NMR and mass spectra analysis. The
      cytotoxic activity of the complex on HL-60 and K562 human leukemia cell lines has
      been investigated by assessing vital cellular mechanisms, such as the metabolic
      activity (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; MTT) and
      the proliferation capacity (growth curves) of leukemia cells, as well as the
      structural integrity of cell membrane (trypan blue assay). The complex exerts an
      increased antiproliferative effect primarily on HL60 human leukemia cells,
      compared to ascorbic acid alone, as well as an inhibitory effect on necrosis
      caused by ascorbic acid. Its effect on K562 cells concerns mainly its inhibitory
      effect upon cell necrosis induced by ascorbic acid alone. Our results support a
      concentration- and time-dependent enhanced antileukemic effect of the complex,
      suggesting its significance as a promising tool in the confrontation of leukemia.

PMID- 21194614
TI  - Organogallium(III) complexes as apoptosis promoting anticancer agents for head
      and neck squamous cell carcinoma (HNSCC) cell lines.
AB  - Organogallium(III) dinuclear (1-9) and tetranuclear (10) complexes present
      potential therapeutic agents for the treatment of various types of cancer. The
      antiproliferative activity of 1-10 was evaluated with cell lines of head and neck
      squamous cell carcinomas, e.g. HN (soft palate), Cal27, Cal33 (tongue) and FaDu
      (hypopharynx) cell lines. The activity of compound 8 is comparable with that of
      cisplatin on cell line Cal27 (IC(50) 4.6 MUM for both compounds). The mode of
      cell death induced, caspase activity and cell cycle analysis were evaluated for
      potential hit compounds 3, 5 and 8 Potential hit compounds 3, 5 and 8 were
      further evaluated for the mode of cell death, caspase activity and cell cycle
      analysis. Apoptosis induced by compounds 3, 5 and 8 on Cal27 and FaDu cells was
      confirmed by DNA laddering , as well as acridine orange (AO) and ethidium bromide
      (EB) double staining. These compounds (3, 5 and 8) induced caspase-independent
      apoptosis (within 4 h of action) in cell line Cal27. Extrinsic-mediated apoptosis
      associated with caspase 8 and 3 activation is the main mode of cytotoxicity
      induced on FaDu cells by compounds 3, 5 and 8. Cell cycle perturbations caused by
      these compounds are also observed. Our data suggest that compounds 3, 5 and 8
      should be studied further for the treatment of head and neck cancer.

PMID- 21194615
TI  - Potential new inorganic antitumour agents from combining the anticancer
      traditional Chinese medicine (TCM) matrine with Ga(III), Au(III), Sn(IV) ions,
      and DNA binding studies.
AB  - Three new compounds of Ga(III), Au(III), Sn(IV) with matrine (MT), [H
      MT][GaCl(4)] (1), [H-MT][AuCl(4)] (2) and [Sn(H-MT)Cl(5)] (3), have been
      synthesized and characterized by elemental analysis, IR, ESI-MS and single
      crystal X-ray diffraction methods. The crystal structural analyses indicate that
      1 and 2 are ionic compounds, whereas 3 is a tin(IV) complex formed by the
      monodentate MT via its carbonyl oxygen atom of MT coordinating to Sn(IV). Their
      in vitro cytotoxicity towards eight selected tumour cell lines has been evaluated
      by MTT (3-[4,5-Dimentylthiazole-2-yl]-2,5-diphenpyltetra-zolium bromide) method,
      and compounds 1 and 2 exhibit enhanced activity, such as 1 to SW480, 2 to HeLa,
      HepG2 and MCF-7, which exceeds matrine and cisplatin, and display synergistic
      contribution of their components. The cell cycle analyses show that compounds 1,
      3 and MT exhibit cell cycle arrest at the G(2)/M phase. Interactions of these
      compounds with calf thymus DNA (ct-DNA) have been investigated by spectroscopic
      analyses. The planar extension of the intercalative metal-matrine compounds
      increases the interaction of the metal-matrine with DNA, indicating that the
      cationic metal ions and configuration of the intercalated metal-matrine will
      affect the extent of interaction. Compound 2, [H-MT][AuCl(4)], exhibits more
      intensive binding ability to DNA, which may correlate with intercalation and
      other action mode. The circular dichroism spectra of the ct-DNA bound with metal
      MT compounds also suggest that ct-DNA interacted with 1, 2, 3 does not influence
      its secondary structure. Furthermore, both compounds 1 and 2 exhibit effective
      inhibition ability to topoisomerase (TOPO I) at concentration of 50 MUM, while
      matrine and compound 3 do not.

PMID- 21194616
TI  - New glycoside derivatives of carnosine and analogs resistant to carnosinase
      hydrolysis: synthesis and characterization of their copper(II) complexes.
AB  - Carnosine (beta-alanyl-L-histidine) is an endogenous dipeptide widely and
      abundantly distributed in muscle and nervous tissues of several animal species.
      Many functions have been proposed for this compound, such as antioxidant and
      metal ion-chelator properties. However, the main limitation on therapeutic use of
      carnosine on pathologies related to increased oxidative stress and/or metal ion
      dishomeostasis is associated with the hydrolysis by the specific dipeptidase
      carnosinase. Several attempts have been made to overcome this limitation. On this
      basis, we functionalized carnosine and its amide derivative with small sugars
      such as glucose and lactose. The resistance of these derivatives to the
      carnosinase hydrolysis was tested and compared with that of carnosine. We found
      that the glycoconjugation protects the dipeptide moiety from carnosinase
      hydrolysis, thus potentially improving the availability of carnosine. The
      copper(II) binding properties of all the new synthesized compounds were
      investigated by spectroscopic (UV-Visible and circular dichroism) and ESI-MS
      studies. Particularly, the new family of amide derivatives that are not
      significantly hydrolyzed by carnosinase is a very promising class of carnosine
      derivatives. The sugar moiety can act as a recognition element. These new
      derivatives are potentially able to act as chelating agents in the development of
      clinical approaches for the regulation of metal homeostasis in the field of
      medicinal inorganic chemistry.

PMID- 21194617
TI  - Radical production by hydrogen peroxide/bicarbonate and copper uptake in
      mammalian cells: modulation by Cu(II) complexes.
AB  - The presence of the bicarbonate/carbon dioxide pair is known to accelerate the
      transition metal ion-catalysed oxidation of various biotargets. It has been shown
      that stable Cu(II) complexes formed with imine ligands that allow redox cycling
      between Cu(I) and Cu(II) display diverse apoptotic effects on cell cultures. It
      is also reported that Cu(II)-tetraglycine can form a stable Cu(III) complex. In
      the present study, radical generation from H(2)O(2) and H(2)O(2)/HCO(3)(-) in the
      presence of these two different classes of Cu(II) complexes was evaluated by
      monitoring the oxidation of dihydrorhodamine 123 and NADH and by the quantitative
      determination of thiobarbituric acid reactive substances (TBARs method). Cu(II)
      imine complexes produced low levels of reactive species whereas Cu(II)-Gly
      derived complexes, as well as the free Cu(II) ion, produced oxygen-derived
      radicals in significantly larger amounts. The effects of these two classes of
      complexes on mammalian tumour cell viability were equally distinct, in that
      Cu(II)-imine complexes caused apoptosis, entered in cell and remained almost
      unaffected in high levels whilst, at the same concentrations, Cu(II)-Gly peptide
      complexes and Cu(II) sulphate stimulated cell proliferation, with the cell
      managing copper efficiently. Taken together, these results highlight the
      different biological effects of Cu(II) complexes, some of which have been
      recently studied as anti-tumour drugs and radical system generators, and also
      update the effects of reactive oxygen species generation on cell cycle control.

PMID- 21194618
TI  - The triphenyltin(VI) complexes of NSAIDs and derivatives. Synthesis, crystal
      structure and antiproliferative activity. Potent anticancer agents.
AB  - The novel triphenyltin(IV) esters of flufenamic acid (1), Hflu, [Ph(3)Sn(flu)]
      (2), and of [2-(2,3-dichlorophenylamino)benzoic acid] (3), Hdcpa, [Ph(3)Sn(dcpa)]
      (4) have been structurally characterized by means of vibrational and (1)H, (13)C
      NMR spectroscopic studies. The crystal and molecular structures of
      [SnPh(3)(dcpa)(DMSO)] 4a are described. The molecular structure of 4a reveals
      that the Sn atom has a distorted trigonal bipyramidal coordination geometry with
      equatorial phenyl groups and the carboxylate and dimethylsulfoxide oxygen atoms
      occupying axial positions. The crystal structure of 4a is self-assembled by C-H
      pi and pi-pi stacking interactions. The in vitro cytotoxic activity of 1-4 and of
      the related non-steroidal anti-inflammatory drugs, NSAIDs, [2-(2,6
      dimethylphenylamino)benzoic acid], Hdmpa (5), [Ph(3)Sn(dmpa)] (6), [2-(2,3
      dimethylphenylamino)benzoic acid], mefenamic acid, Hmef (7) and [Ph(3)Sn(mef)]
      (8) has been evaluated against the cancer cell lines MCF-7, T-24, A-549 and L
      929. The ligands exhibited very poor cytotoxic activity against the four cancer
      cell lines. Complex 6 exhibits the highest activity and selectivity against A-549
      and MCF-7 cancer cell lines and complex 8 the highest activity and selectivity
      against T-24 cancer cell line. The cytotoxic results indicate that coupling of
      Hdmpa and Hmef with R(3)Sn(IV) metal center results in complexes with important
      biological properties and remarkable cytotoxic activity, since they display
      IC(50) values in a MUMU range better to that of the antitumor drug cis-platin.
      Complexes 6 and 8 are considered as excellent antitumor compounds and the results
      of this study represent the discovery of triphenyltin(IV) esters as a potential
      novel class of anticancer agents.

PMID- 21194619
TI  - Non-reductive iron release from horse spleen ferritin using desferoxamine
      chelation.
AB  - The rate of Fe(3+) release from horse spleen ferritin (HoSF) was measured using
      the Fe(3+)-specific chelator desferoxamine (DES). The reaction consists of two
      kinetic phases. The first is a rapid non-linear reaction followed by a slower
      linear reaction. The overall two-phase reaction was resolved into three kinetic
      events: 1) a rapid first-order reaction in HoSF (k(1)); 2) a second slower first
      order reaction in HoSF (k(2)); and 3) a zero-order slow reaction in HoSF (k(3)).
      The zero-order reaction was independent of DES concentration. The two first-order
      reactions had a near zero-order dependence on DES concentration and were
      independent of pH from 6.8 to 8.2. The two first-order reactions accounted for 6
      9 rapidly reacting Fe(3+) ions. Activation energies of 10.5+/-0.8, 13.5+/-2.0 and
      62.4+/-2.1kJ/mol were calculated for the kinetic events associated with k(1),
      k(2), and k(3), respectively. Iron release occurs by: 1) a slow zero-order rate
      limiting reaction governed by k(3) and corresponding to the dissociation of
      Fe(3+) ions from the FeOOH core that bind to an Fe(3+) binding site designated as
      site 1 (proposed to be within the 3-fold channel); 2) transfer of Fe(3+) from
      site 1 to site 2 (a second binding site in the 3-fold channel) (k(2)); and 3)
      rapid iron loss from site 2 to DES (k(1)).

PMID- 21194620
TI  - Cu2+ and Ni2+ interactions with N-terminal fragments of Hpn and Hpn-like proteins
      from Helicobacter pylori: unusual impact of poly-Gln sequence on the complex
      stability.
AB  - The N-terminal protected and unprotected peptides MAHHEEQHG-NH(2), Ac-MAHHEEQHG
      NH(2) from Hpn (Helicobacter histidine-rich protein) and MAHHEQQQQQQA-NH(2), Ac
      MAHHEQQQQQQA-NH(2) from Hpn-like protein, respectively, were synthesized and
      their interactions with Cu(2+) and Ni(2+) ions were studied by potentiometric, UV
      visible, CD, and EPR techniques. The studies have shown that because of their
      albumin-like sequence, unprotected peptides are very effective chelating agents
      for both studied metals. The presence of the hexa-glutamine sequence has very
      distinct impact on the stability of the complexes formed even if direct
      interactions with metal ions were not found. The much more effective Ni(2+)
      binding by Hpn-like N-terminal domain when compared to Hpn protein could be
      critical for different biological functions played by both proteins.

PMID- 21194621
TI  - Hydrolysis of phosphatidylcholine by cerium(IV) releases significant amounts of
      choline and inorganic phosphate at lysosomal pH.
AB  - Niemann-Pick disease and drug-induced phospholipidosis are examples of lysosomal
      storage disorders in which serious respiratory infections are brought on by high
      levels of the phospholipid phosphatidylcholine in the acidic lamellar bodies and
      lysosomes of pulmonary cells. One approach to developing an effective therapeutic
      agent could involve the use of a metal to preferentially hydrolyze phospholipid
      phosphate ester bonds at mildly acidic, lysosomal pH values (~pH 4.8). Towards
      this end, here we have investigated phosphatidylcholine hydrolysis by twelve
      metal ion salts at 60 degrees C. Using a malachite green/molybdate-based
      colorimetric assay to detect inorganic phosphate released upon metal-assisted
      phosphate ester bond hydrolysis, Ce(IV) was shown to possess outstanding
      reactivity in comparison to the eleven other metals. We then utilized cerium(IV)
      to hydrolyze phosphatidylcholine at normal, core body temperature (37 degrees C).
      The malachite green/molybdate assay was used to quantitate free phosphate and an
      Amplex(r) Red-based colorimetric assay and matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry were employed to detect choline.
      Ce(IV) hydrolyzed phosphatidylcholine more efficiently at lysosomal pH: i.e., at
      a Triton X-100:phosphatidylcholine molar mixing ratio of 1.57, yields of choline
      and phosphate were 51+/-4% and 40+/-4% at ~pH 4.8, compared to 28+/-4% and 27+/
      5% at ~pH 7.2.

PMID- 21194622
TI  - From hydrolytically labile to hydrolytically stable Ru(II)-arene anticancer
      complexes with carbohydrate-derived co-ligands.
AB  - The synthesis, characterization, reactivity and in vitro anticancer activity of a
      series of Ru(II)-arene complexes with carbohydrate-derived phosphite and
      biscarboxylato co-ligands are reported. The compounds were characterized by NMR
      spectroscopy and electrospray ionization (ESI) mass spectrometry, and the
      molecular structures of oxalato(eta(6)-p-cymene)(3,5,6-bicyclophosphite-1,2-O
      isopropylidene-alpha-D-glucofuranoside)ruthenium(II) and oxalato(eta(6)-p
      cymene)(3,5,6-bicyclophosphite-1,2-O-cyclohexylidene-alpha-D
      glucofuranoside)ruthenium(II) were determined by X-ray diffraction analysis. In
      contrast to their dichlorido counterparts, the biscarboxylato complexes did not
      exhibit significant reactivity towards biomolecules, such as cysteine,
      methionine, ubiquitin or the DNA model 5'-GMP, and resist hydrolysis; no
      hydrolytic species were detected by (1)H and (31)P{(1)H} NMR spectroscopy over
      several days. These structural alterations led to a decrease in the tumor
      inhibiting potency of the compounds in human cancer cell lines.

PMID- 21194623
TI  - In vitro antitumour activity of water soluble Cu(I), Ag(I) and Au(I) complexes
      supported by hydrophilic alkyl phosphine ligands.
AB  - Hydrophilic, monocationic [M(L)(4)]PF(6) complexes (M = Cu or Ag; L: thp =
      tris(hydroxymethyl)phosphine, L: PTA = 1,3,5-triaza-7-phosphaadamantane, L: thpp
      = tris(hydroxypropyl)phosphine) were synthesized by ligand exchange reaction
      starting from [Cu(CH(3)CN)(4)]PF(6) or AgPF(6) precursors at room temperature in
      the presence of an excess of the relevant phosphine. The related [Au(L)(4)]PF(6)
      complexes (L = thp, PTA or thpp) were synthesized by metathesis reactions
      starting from [Au(L)(4)]Cl at room temperature in the presence of equimolar
      quantity of TlPF(6). The three series of complexes [M(L)(4)]PF(6) were tested as
      cytotoxic agents against a panel of several human tumour cell lines also
      including a defined cisplatin resistant cell line. These investigations have been
      carried out in comparison with the clinically used metallodrug cisplatin and
      preliminary structure-activity relationships are presented. The best results in
      terms of in vitro antitumour activity were achieved with metal-thp species and,
      among the coinage metal complexes, copper derivatives were found to be the most
      efficient drugs. Preliminary studies concerning the mechanism of action of these
      [M(L)(4)]PF(6) species pointed to thioredoxin reductase as one of the putative
      cellular targets of gold and silver complexes and provided evidence that copper
      derivatives mediated their cytotoxic effect through proteasome inhibition.

PMID- 21194624
TI  - DNA interaction and cytotoxicity studies of new ruthenium(II) cyclopentadienyl
      derivative complexes containing heteroaromatic ligands.
AB  - Four ruthenium(II) complexes with the formula [Ru(eta(5)
      C(5)H(5))(PP)L][CF(3)SO(3)], being (PP = two triphenylphosphine molecules), L = 1
      benzylimidazole, ; (PP = two triphenylphosphine molecules), L = 2,2'bipyridine, ;
      (PP = two triphenylphosphine molecules), L = 4-Methylpyridine, ; (PP = 1,2
      bis(diphenylphosphine)ethane), L = 4-Methylpyridine, , were prepared, in view to
      evaluate their potentialities as antitumor agents. The compounds were completely
      characterized by NMR spectroscopy and their crystal and molecular structures were
      determined by X-ray diffraction. Electrochemical studies were carried out giving
      for all the compounds quasi-reversible processes. The images obtained by atomic
      force microscopy (AFM) suggest interaction with pBR322 plasmid DNA. Measurements
      of the viscosity of solutions of free DNA and DNA incubated with different
      concentrations of the compounds confirmed this interaction. The cytotoxicity of
      compounds 1234 was much higher than that of cisplatin against human leukemia
      cancer cells (HL-60 cells). IC(50) values for all the compounds are in the range
      of submicromolar amounts. Apoptotic death percentage was also studied resulting
      similar than that of cisplatin.

PMID- 21194625
TI  - Strategies for the covalent conjugation of a bifunctional chelating agent to
      albumin: synthesis and characterization of potential MRI contrast agents.
AB  - With the purpose to develop macromolecular magnetic resonance imaging contrast
      agents, we herein report three different synthetic approaches to the covalent
      attachment of bifunctional chelating agents to human serum albumin followed by
      coordination to contrast enhancing gadolinium(III). Applied methods cover active
      ester-mediated conjugation, linkage through glutaryl spacer, as well as the
      connection by the employment of glutaraldehyde. The content of gadolinium(III)
      was evaluated by inductively-coupled-plasma mass-spectrometry (ICP-MS)
      measurements and indicated reproducible amounts of conjugated contrast enhancing
      material. Small angle X-ray scattering (SAXS) experiments provided the size and
      altered shape of the gadolinium loaded proteins in comparison to unmodified
      albumin. Finally, the magnetic resonance properties of the protein conjugates
      were evaluated. The results indicated suitability of the gadolinium(III) loaded
      protein conjugates for use as macromolecular contrast agents in magnetic
      resonance imaging (MRI).

PMID- 21194626
TI  - One pot synthesis of Cu(II) 2,2'-bipyridyl complexes of 5-hydroxy-hydurilic acid
      and alloxanic acid: synthesis, crystal structure, chemical nuclease activity and
      cytotoxicity.
AB  - A barbiturate derivative [1,5-dihydro-5-[5-pyrimidine-2,4(1H,3H)-dionyl]-2H
      chromeno[2,3-d] pyrimidine-2,4(3H)-dione] (LH(4)) was allowed to react with 2,2'
      bipyridyl-dinitrato-Copper(II)-dihydrate which provides two complexes,
      characterized as [Cu(bpy)(L1)].3H(2)O (1) and [Cu(bpy)(L2)].H(2)O (2), where bpy
      = 2,2'-bipyridine, L1 = 5-hydroxy-hydurilic acid and L2 = alloxanic acid. In a
      separate reaction of LH(4) with Cu(NO(3))(2).H(2)O another type of complex
      [Cu(LH(3))(2).(H(2)O)(2)].4H(2)O (3) is formed. The complexes were characterized
      by single crystal X-ray crystallography, physicochemical and electrochemical
      studies. The interaction of complexes 1 and 3 with DNA was monitored using
      absorption and emission titrations as well as circular dichroism spectroscopy.
      The complexes were found to cleave supercoiled plasmid DNA to nicked circular and
      linear DNA. Complexes 1 and 3 were also tested against T-cell lymphoma (Dalton
      lymphoma DL) and showed significant cytotoxic activity with IC(50) values of ~9.0
      nM and 0.6 nM.

PMID- 21194627
TI  - A large scale enzyme screen in the search for new methods of silicon-oxygen bond
      formation.
AB  - Biotransformations make use of biological systems to catalyze or promote specific
      chemical reactions. Transformations that utilize enzymes as "greener" and milder
      catalysts compared to traditional reaction conditions are of particular interest.
      Recently, organosilicon compounds have begun to be explored as non-natural
      enzymatic substrates for biotransformations. The aims of this study were to
      screen readily available (approximately eighty) enzymes for their ability to
      catalyze in vitro siloxane bond formation under mild reaction conditions using a
      model monoalkoxysilane as the substrate and to make a preliminary evaluation of
      potential factors that might lead to activity or inactivity of a particular
      enzyme. Several new hydrolase enzymes were observed to catalyze the formation of
      the condensation product when compared to peptide controls, or buffer solutions
      at the same pH, as judged from quantitative analyses by gas chromatography.
      Aspergillus ficuum phytase, Aspergillus niger phytase, chicken egg white
      lysozyme, porcine gastric mucosa pepsin, and Rhizopus oryzae lipase all catalyzed
      the condensation of silanols in aqueous media. Factors involved in determining
      the activity of an enzyme towards silanol condensation appear to include: the
      presence of imidazole and hydroxyl functions in the active site; solvent; the
      presence of water; the surface properties of the enzyme; possible covalent
      inhibition; and steric factors in the substrate.

PMID- 21194628
TI  - The mechanism of antimalarial action of [Au(CQ)(PPh(3))]PF(6): structural effects
      and increased drug lipophilicity enhance heme aggregation inhibition at
      lipid/water interfaces.
AB  - The mechanism of antimalarial action of [Au(CQ)(PPh(3))]PF(6) (1), which is
      active in vitro against CQ-resistant P. falciparum and in vivo against P.
      berghei, has been investigated in relation to hemozoin formation and DNA as
      possible important targets. Complex 1 interacts with heme and inhibits beta
      hematin formation both in aqueous medium and near water/n-octanol interfaces at
      pH ~5 to a greater extent than chloroquine diphosphate (CQDP) or other known
      metal-based antimalarial agents; the higher inhibition activity is probably
      related to the higher lipophilicity observed for 1 through partition coefficient
      measurements at low pH, with respect to CQDP. The interactions of complex 1 with
      DNA were explored using spectrophotometric and fluorimetric titrations, circular
      dichroism spectroscopy, viscosity and melting point studies, as well as
      electrophoresis and covalent binding assays. The experimental data indicate that
      complex 1 interacts with DNA predominantly by intercalation and electrostatic
      association of the CQ moiety, similarly to free CQDP, while no covalent metal-DNA
      binding seems to take place. The most likely antimalarial mechanism for complex 1
      is thus heme aggregation inhibition; the high activities observed against
      resistant parasites are probably due to the structural modification of CQ
      introduced by the presence of the gold-triphenylphosphine fragment, together with
      the enhanced lipophilic character.

PMID- 21194629
TI  - Synthesis and kinetic evaluation of a trifunctional enzyme mimic with a
      dimanganese active centre.
AB  - Glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT) play
      crucial roles in the metabolism and homeostasis of reactive oxygen species (ROS)
      in living organisms. From examination of the steady state and pre-steady state
      kinetic behavior of natural GPX it was found that, in contrast to accepted
      theories, the affinity of the enzyme for H(2)O(2) rather than reduced glutathione
      (GSH) most significantly affects its kinetic behavior. Consequently, an enzyme
      mimic was produced with a similar affinity for the substrate H(2)O(2). A
      salicylaldehyde Schiff base containing a dimanganese centre was selected as a
      precursor, because it has high H(2)O(2)-binding affinity for such a relatively
      small molecule and similar catalytic activity to that of SOD and CAT. Selenium
      was also incorporated into the catalytic center to provide activity similar to
      that of GPX, and thus trifunctional enzymatic activity. The K(mH2O2) of the mimic
      (7.32*10(-2) mM) was found quite close to that of natural enzyme (1.0*10(-2) mM),
      indicating that the affinity of the mimic to H(2)O(2) was successfully increased
      to approach natural GPX. The steady state kinetic performance of the enzyme mimic
      showed that the ratio between k(cat)/K(mGSH) and k(cat)/ K(mH2O2) was quite
      similar to that of native GPX, indicating that the Mn(III)(2)(L-Se-SO(3)Na) had
      the same selectivity for both substrates GSH and H(2)O(2) as native GPX, which
      put it among the best existing GPX mimics. Moreover, the new mimic was confirmed
      to strongly inhibit lipid peroxidation and mitochondrial swelling, probably due
      to the synergism between the three antioxidant enzymatic activities.

PMID- 21194630
TI  - Reduction of oxaporphyrin ring of CO-bound alpha-verdoheme complexed with heme
      oxygenase-1 by NADPH-cytochrome P450 reductase.
AB  - Heme oxygenase (HO) catalyses the degradation of heme to biliverdin, carbon
      monoxide (CO) and ferrous iron via three successive monooxygenase reactions,
      using electrons provided by NADPH-cytochrome P450 reductase (CPR) and oxygen
      molecules. For cleavage of the oxaporphyrin ring of ferrous alpha-verdoheme, an
      intermediate in the HO reaction, involvement of a verdoheme pi-neutral radical
      has been proposed. To explore this hypothetical mechanism, we performed
      electrochemical reduction of ferrous alpha-verdoheme-rat HO-1 complex under
      anaerobic conditions. Upon binding of CO, an O(2) surrogate, the midpoint
      potential for one-electron reduction of the oxaporphyrin ring of ferrous alpha
      verdoheme was increased from -0.465 to -0.392 V vs the normal hydrogen electrode.
      Because the latter potential is close to that of the semiquinone/reduced redox
      couple of FAD in CPR, the one-electron reduction of the oxaporphyrin ring of CO
      bound verdoheme complexed with HO-1 is considered to be a thermodynamically
      likely process. Indeed the one-electron reduced species, [Fe(II)(verdoheme*)],
      was observed spectroscopically in the presence of CO in both NADPH/wild-type and
      FMN-depleted CPR systems under anaerobic conditions. Under physiological
      conditions, therefore, it is possible that O(2) initially binds to the ferrous
      iron of alpha-verdoheme in its complex with HO-1 and an electron is subsequently
      transferred from CPR, probably via FAD, to the oxaporphyrin ring.

PMID- 21194631
TI  - The cyclopeptides with the multi-His motif as ligands for copper(II).
AB  - The coordination properties of cyclic octapeptides with multi-His motif: c(His
      Gly-His-Xaa-His-Gly-His-Xaa) where Xaa = Asp or Lys, were investigated. The
      binding abilities of this peptides towards Cu(II) ions were studied by using
      different analytic methods as: potentiometry, spectroscopy and mass spectrometry.
      The obtained results show that the studied peptides in physiological related pH
      prefer formation of the species with the {4N(Im)} binding mode. The efficiency of
      Cu(II) binding depends on additional side chain groups Asp or Lys. Additionally
      the analysis of results for His containing cyclopeptides with different numbers
      of amino acid residues in cyclopeptide ring e.g. four, eight shows that in higher
      pH in both cases the binding by four amide nitrogens is not observed in the case
      of alpha-amino acid peptides.

PMID- 21194632
TI  - Vanadium polypyridyl compounds as potential antiparasitic and antitumoral agents:
      new achievements.
AB  - In the search for new therapeutic tools against diseases produced by
      kinetoplastid parasites five vanadyl complexes, [V(IV)O(L-2H)(phen)], including
      1,10-phenanthroline (phen) and tridentate salicylaldehyde semicarbazone
      derivatives as ligands have been synthesized and characterized in the solid state
      and in solution by using different techniques. EPR suggested a distorted
      octahedral geometry with the tridentate semicarbazone occupying three equatorial
      positions and phen coordinated in an equatorial/axial mode. The compounds were
      evaluated in vitro on epimastigotes of Trypanosoma cruzi, causative agent of
      Chagas disease, Leishmania panamensis and Leishmania chagasi and on tumor cells.
      The complexes showed higher in vitro anti-trypanosomal activities than the
      reference drug Nifurtimox (IC(50) values in the range 1.6-3.8 MUM) and increased
      activities in respect to the free semicarbazone ligands. In vitro activity on
      promastigote and amastigote forms of Leishmania showed interesting results. The
      compounds [VO(L1-2H)(phen)] and [VO(L3-2H)(phen)], where L1 = 2
      hydroxybenzaldehyde semicarbazone and L3 = 2-hydroxy-3-methoxybenzaldehyde
      semicarbazone, resulted active (IC(50) 2.74 and 2.75 MUM, respectively, on
      promastigotes of L. panamensis; IC(50) 19.52 and 20.75 MUM, respectively, on
      intracellular amastigotes of L. panamensis) and showed low toxicity on THP-1
      mammalian cells (IC(50) 188.55 and 88.13 MUM, respectively). In addition, the
      complexes showed cytotoxicity on human promyelocytic leukemia HL-60 cells with
      IC(50) values of the same order of magnitude as cisplatin. The interaction of the
      complexes with DNA was demonstrated by different techniques, suggesting that this
      biomolecule could be a potential target either in the parasites or in tumor
      cells.

PMID- 21194633
TI  - Macrocyclic complexes of scandium radionuclides as precursors for diagnostic and
      therapeutic radiopharmaceuticals.
AB  - The aim of this study was to evaluate new ligands which can be applied for
      labeling biomolecules with scandium radionuclides. Two radionuclides of scandium,
      (47)Sc and (44)Sc, are perspective radioisotopes for radiotherapy and diagnostic
      imaging. (47)Sc decays with a half-life of 3.35 days and a maximum beta(-) energy
      of 600 keV and could be an alternative to carrier added (177)Lu radionuclide for
      targeted radionuclide therapy. Another scandium radionuclide (44)Sc (t(1/2) =
      3.92 h) is an ideal beta(+) emitter for PET diagnosis. It can be obtained as a
      daughter of the long-lived (44)Ti (t(1/2) = 60.4 y) from (44)Ti/(44)Sc generator.
      For complexation of scandium radionuclides macrocyclic ligands having a cavity
      size similar to Sc(3+) ionic radius were selected: 1,4,7,10-tetraazacyclododecane
      1,4,7,10-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-1,4,7 triacetic acid
      (NOTA), 1,4,7-triazacyclodecane-1,4,7 triacetic acid and 1,4,7
      triazacycloundecane triacetic acid, and analogs of NOTA with 10, 11 and 12 atoms
      of the carbon in the ring. Our results have shown that from the studied
      macrocyclic ligands studied DOTA is most efficient for binding scandium
      radionuclides (44)Sc and (47)Sc to biomolecules. The determined stability
      constant of Sc-DOTA complex logK = 27.0 is comparable with stability constants
      for Y(3+) and heaviest lanthanides but is higher than those for In(3+) and
      Ga(3+). Also (46)Sc-DOTATATE conjugate exhibits high stability in-vitro studies.
      The (13)C NMR studies have shown that Sc-DOTA like Lu-DOTA forms in solution
      complexes with eight-coordination geometry. The lipophilicity of Sc-DOTATATE is
      nearly identical to that of Lu-DOTATATE, which suggests similar receptor affinity
      of both radioconjugates.

PMID- 21194634
TI  - Oxidative degradation of Remazol Turquoise Blue G 133 by soybean peroxidase.
AB  - Reactive dyes are widely employed in textile industries and their removal from
      wastewaters is a relevant environmental problem. In addition to chemical and
      physical methods, several bioremediation approaches, involving intact micro
      organisms or isolated enzymes, have been proposed to decolorize dye solutions. In
      this paper, we report the complete and fast decolourization of a Cu(II)
      phthalocyanine based reactive dye (Remazol Turquoise Blue G 133) by means of the
      soybean peroxidase/H(2)O(2) system. The oxidative degradation of the dye in
      aqueous solution at 25 degrees C was studied as function of pH, revealing a
      quantitative decolourization yield at acidic pH values with a maximum of activity
      at pH 3.3. The reaction products were identified and characterized by HPLC-diode
      array detector (DAD)-mass spectrometry (MS), ionic chromatography and EPR
      techniques. This analysis showed that the enzyme catalyses the breaking of the
      phthalocyanine ring producing sulfophthalimide as the main degradation product,
      and the release of stoichiometric amount of ammonium and Cu(II) ions.

PMID- 21194635
TI  - Current management of selected vascular emergencies.

PMID- 21194636
TI  - Ruptured AAA: open surgical management.
AB  - Ruptured abdominal aorta aneurysm (rAAA) is the 13th leading cause of death in
      the United States. Despite many advances in the field of vascular surgery, the
      improvement in mortality rates of rAAA have been very modest. Although
      endovascular repair has surpassed open repair for elective AAA repair in the
      United States, open rAAA repair remains the most common therapy for this
      devastating vascular emergency. In this article, we discuss open surgical
      management for rAAA. We also describe a fast-track algorithm we have developed at
      the University of Massachusetts where open and endovascular repairs play equally
      important roles in management of rAAA.

PMID- 21194637
TI  - Ruptured abdominal aortic aneurysm: endovascular program development and results.
AB  - Improvements in endovascular technology and techniques have allowed us to treat
      patients in ways we never thought possible. Today endovascular treatment of
      ruptured abdominal aortic aneurysms is associated with markedly decreased
      morbidity and mortality when compared to the open surgical approach, yet there
      are several fundamental obstacles in our ability to offer these endovascular
      techniques to most patients with ruptured aneurysms. This article will focus on
      the technical aspects of endovascular aneurysm repair for rupture, with
      particular attention to developing a standardized multidisciplinary approach that
      will help ones ability to deal with not just the technical aspects of these
      procedures, but also address some of the challenges including: the availability
      of preoperative CT, the choice of anesthesia, percutaneous vs. femoral cut-down
      approach, use of aortic occlusion balloons, need for bifurcated vs. aorto
      uniiliac stentgrafts, need for adjunctive procedures, diagnosis and treatment of
      abdominal compartment syndrome, and conversion to open surgical repair.

PMID- 21194638
TI  - Current management of traumatic thoracic aortic injury.
AB  - Traumatic aortic rupture is a devastating injury that is difficult to manage
      because of the need to approach aortic repair, often in concert with management
      of complex associated injuries to nonvascular organ systems. Traditional open
      repair, while effective in the long-term, is associated with a periprocedural
      mortality between 10% and 20%, along with a 5% risk of stroke and up to a 5% risk
      of spinal chord ischemia. The advent of endovascular stent graft repair has
      allowed single centers to cut periprocedural mortality in half and decrease the
      risk of major neurologic events to <2%. It is unlikely that a multicenter
      prospective randomized trial will ever be performed to evaluate these two
      procedures. However, several large meta-analyses have been published recently,
      along with a clinical practice guideline from the Society for Vascular Surgery.
      The purpose of this article is to review the trends and current concepts in the
      management of traumatic rupture of the thoracic aorta.

PMID- 21194639
TI  - Clotting problems: diagnosis and management of underlying coagulopathies.
AB  - Vessel wall injury, stasis, and blood hypercoagulable state are major
      predisposing factors of thrombosis. Although, a procoagulable factor is found in
      half of patients with venous thromboembolism, relatively little is known about
      coagulopathies that predispose to arterial thromboembolism or unexplained
      arterial revascularization thrombosis. Those hypercoagulable states can be
      inherited or acquired and related to either an increase of a procoagulable factor
      or a decrease of an anticoagulation agent. However, most thrombotic episodes seem
      to occur with additive combination of acquired and inherited predisposing
      factors. Therefore, controversy exists as to which patients and family members to
      test for thrombophilia and which patients to treat with life-long
      anticoagulation. The aim of this review is to provide a practical overview with
      guidelines for detecting, and treatment of, the principal underlying
      coagulopathies that a vascular surgeon should be aware of in his/her practice and
      for the care of patients with vascular disease.

PMID- 21194640
TI  - Thrombolysis for lower-extremity deep vein thrombosis.
AB  - Elimination of the embolic potential of existing thrombus, restoration of
      unobstructed flow, prevention of further thrombosis, and preservation of venous
      valve function are the ideal goals of therapy for acute deep vein thrombosis
      (DVT). Meeting these goals will not only prevent pulmonary embolus, but will also
      minimize long-term sequelae of venous hypertension and development of
      postthrombotic syndrome (PTS). Treatment strategies aimed at eliminating or
      reducing risk of PTS should focus on preserving valvular function and eliminating
      risk of continued venous obstruction after acute DVT. Thrombolytic agents are an
      attractive form of early therapy because they have the ability to eliminate
      obstructive thrombus in the deep veins, and should therefore help provide
      protection against PTS. Perceived benefits of early and rapid recanalization in
      preserving valve function have been the basis for lytic therapy to treat acute
      DVT. Data from the National Venous Registry and subsequent reports on the role of
      catheter-directed thrombolysis for treatment of acute lower-extremity DVT
      indicate that the technique is safe and effective in select patients. More
      recently, implementation of percutaneous mechanical devices designed to quickly
      remove acute thrombus has had a significant impact on time and cost of catheter
      directed thrombolysis procedure. Although the long-term benefits of this form of
      therapy are not yet completely known, the Venous Registry can serve as a guide to
      the judicious selection of patients who will most benefit from this aggressive
      form of therapy.

PMID- 21194641
TI  - Management of civilian and military vascular trauma: lessons learned.
AB  - Management of vascular trauma has evolved tremendously since the turn of the
      20(th) century. The lessons from each major military conflict over the past 100
      years have refined our understanding of how to care for soldiers and civilians
      with vascular injuries. The recent wars in Iraq and Afghanistan have likewise
      improved our strategy for treating victims of vascular trauma. Understanding the
      principles that guide management of vascular injuries will result in preservation
      of life and limb.

PMID- 21194642
TI  - Selective use of endovascular techniques in the management of vascular trauma.
AB  - Endovascular techniques have become crucial to the success of many elective and
      emergent vascular surgical cases. Although diagnostic angiography has always
      played a central role in the evaluation and management of vascular trauma,
      interventions such as stent grafting and coil embolization are increasingly being
      used as treatment modalities. Research exists to support the selective use of
      endovascular techniques in the management of blunt and penetrating vascular
      trauma, and specific scenarios and indications will be reviewed here. To ensure
      the most favorable outcomes, vascular interventionalists must always be aware of
      the limitations of these techniques as well as the limitations facing them in
      their hospital practice environments.

PMID- 21194643
TI  - The problem of plagiarism.
AB  - Plagiarism is a form of research misconduct and a serious violation of the norms
      of science. It is the misrepresentation of another's ideas or words as one's own,
      without proper acknowledgement of the original source. Certain aspects of
      plagiarism make it less straightforward than this definition suggests. Over the
      past 30 years, the U.S. Federal Government has developed and refined its policies
      on misconduct, and Federal agencies, as well as research institutions, have
      established approaches to responding to allegations and instances of plagiarism.
      At present, efforts to avert plagiarism focus on plagiarism-detection software
      and instructional strategies.

PMID- 21194644
TI  - Combating unethical publications with plagiarism detection services.
AB  - About 3,000 new citations that are highly similar to citations in previously
      published manuscripts that appear each year in the biomedical literature
      (Medline) alone. This underscores the importance for the opportunity for editors
      and reviewers to have detection system to identify highly similar text in
      submitted manuscripts so that they can then review them for novelty. New software
      based services, both commercial and free, provide this capability. The
      availability of such tools provides both a way to intercept suspect manuscripts
      and serve as a deterrent. Unfortunately, the capabilities of these services vary
      considerably, mainly as a consequence of the availability and completeness of the
      literature bases to which new queries are compared. Most of the commercial
      software has been designed for detection of plagiarism in high school and college
      papers; however, there is at least 1 fee-based service (CrossRef) and 1 free
      service (etblast.org), which are designed to target the needs of the biomedical
      publication industry. Information on these various services, examples of the type
      of operability and output, and things that need to be considered by publishers,
      editors, and reviewers before selecting and using these services is provided.

PMID- 21194645
TI  - Educational approaches for discouraging plagiarism.
AB  - Suggested approaches to reduce the occurrence of plagiarism in academia,
      particularly among trainees. These include (1) educating individuals as to the
      definition of plagiarism and its consequences through written guidelines, active
      discussions, and practice in identifying proper and improper citation practices;
      (2) distributing checklists that break the writing task into more manageable
      steps, (3) requiring the submission of an outline and then a first draft prior to
      the deadline for a paper; (4) making assignments relevant to individual
      interests; and (5) providing trainees with access to software programs that
      detect plagiarism.

PMID- 21194646
TI  - International perspectives on plagiarism and considerations for teaching
      international trainees.
AB  - In the increasingly global community of biomedical science and graduate science
      education, many US academic researchers work with international trainees whose
      views on scientific writing and plagiarism can be strikingly different from US
      norms. Although a growing number of countries and international professional
      organizations identify plagiarism as research misconduct, many international
      trainees come from research environments where plagiarism is ill-defined and even
      commonly practiced. Two research-ethics educators consider current perspectives
      on plagiarism around the world and contend that US research-training programs
      should focus on trainees' scientific writing skills and acculturation, not simply
      on preventing plagiarism.

PMID- 21194654
TI  - An overview of normal pressure hydrocephalus and its importance: how much do we
      really know?
AB  - Normal pressure hydrocephalus (NPH) is a clinical triad of gait disturbance,
      dementia, and urinary incontinence combined with radiographic findings of
      ventriculomegaly and laboratory findings of normal cerebrospinal fluid pressures.
      Although it was first described by Hakim and Adams in 1965, there is no formal
      definition of NPH, causing discrepancy in its incidence in various studies. This
      ranges from 2 to 20 per million per year. It is estimated to be the cause of
      about 5% of cases of dementia and is one of the few reversible causes of
      dementia. Early diagnosis increases the rate of success to treatment. This makes
      accurate diagnosis and identification of responders to treatment important. There
      have been various studies on NPH in the general population, but not much has been
      said about it in long-term care facilities and the question arises on how many
      cases are missed. If a screening tool is in place to identify possible cases then
      further workup could be done to confirm the diagnosis and determine the need for
      shunting.

PMID- 21194655
TI  - Elders' environs and their end-of-life preferences.
AB  - HYPOTHESIS: Elders' predilections regarding end-of-life interventions vary with
      their living environs. METHODS: Patients in 3 settings--assisted
      living/outpatient, skilled nursing facility (SNF), and acute hospitalization-
      were asked to complete a brief questionnaire. RESULTS: A total of 269 patients
      who averaged 80.0 +/- (SD) 8.1 years, 44% male, 70% white were studied. Eighty
      five patients were outpatient elderly, 101 were hospitalized for acute illnesses,
      and 83 were interviewed in SNFs. Outpatients (44/85; 52%) and acutely ill
      inpatients (40/101; 40%) were more likely than patients residing in SNFs (19/81;
      23%) to choose comfort care only (P = .047) for acute pneumonia requiring
      endotracheal intubation (ETI). Overall, 32% changed their choice for ETI, opting
      for comfort care only if acute pneumonia was followed by disposition to an SNF.
      However, ambulatory and acutely ill elderly patients were 3 times as likely as
      SNF patients to change from aggressive to comfort care if the most likely outcome
      was disposition to an SNF (P < .001). In multivariate regression models, age
      (>80), gender, number of lost ADLs (>2), and self-described quality of life were
      not associated with choosing comfort care instead of ETI, whereas place of
      residence (SNF versus home) was independently associated with choosing ETI (odds
      ratio = 3.5; 95%CI = 1.9-6.4). Similarly, those already living in an SNF were
      more likely to opt for remaining there for advancing dementia (odds ratio = 7.7;
      95%CI = 3.8-15.8). However, choices for ETI did not coincide with choosing an SNF
      for advancing dementia. CONCLUSIONS: Elders residing in nursing homes were more
      likely than ambulatory patients to request invasive end-of-life care, a
      difference that was more pronounced when outcome required disposition to an SNF.
      These preferences were not dependent on patients' self-described disability or
      quality of life. This study suggests that qualitative outcomes matter to patients
      and their choices are associated with their place of residence.

PMID- 21194656
TI  - Effectiveness of short-term interdisciplinary intervention on postacute patients
      in Taiwan.
AB  - OBJECTIVE: To evaluate the effectiveness of community hospital-based postacute
      care (PAC) for frail older patients and to provide a baseline profile of
      functional gain during PAC for use in further long-term outcome studies. DESIGN:
      Prospective cohort study. SETTING: A community hospital in Taiwan. PARTICIPANTS:
      Elderly patients admitted to a community hospital with acute or postacute
      conditions. MEASUREMENTS: Barthel Index, Instrumental Activities of Daily Living,
      Mini-Mental State Examination, and Geriatric Depression Scale. INTERVENTION: A
      comprehensive geriatric assessment-based functional re-ablement program. RESULTS:
      Data were collected for 251 patients recruited between July 2006 and June 2008
      from Taipei Veterans General Hospital and the acute wards of Yuanshan Veterans
      Hospital. Overall, clinical improvement was significant in various dimensions,
      including cognition (Mini-Mental State Examination from 11.9 +/- 8.1 to 15.1 +/-
      8.3, P < .001), physical function (Barthel Index from 42.2 +/- 34.1 to 64.9 +/-
      33.7, P < .001; Lawton-Brody Instrumental Activities of Daily Living from 1.8 +/-
      2.4 to 3.0 +/- 2.8, P < .001), depression (Geriatric Depression Scale from 0.9 +/
      1.9 to 0.6 +/- 1.3, P < .001), ambulation (timed up-and-go test from 16.4 +/-
      19.6 to 10.1 +/- 19.0, P < .001), and nutrition (Mini Nutritional Assessment from
      15.0 +/- 4.2 to 17.4 +/- 3.7, P < .001). CONCLUSION: A short-term inpatient
      physical re-ablement program conducted by an interdisciplinary geriatric team in
      a community hospital can successfully improve the physical and mental function,
      mood, ambulation, and nutritional conditions of postacute patients. Further study
      is needed to evaluate long-term clinical outcomes of patients with different
      rates of functional recovery during treatment in a PAC unit.

PMID- 21194657
TI  - Diabetes mellitus, glycemic control, and pneumonia in long-term care facilities:
      a 2-year, prospective cohort study.
AB  - OBJECTIVE: To determine the relationships among diabetes mellitus (DM), glycemic
      control, and long-term care facility (LTCF)-acquired pneumonia. DESIGN:
      Prospective cohort study. SETTING: Ten private LTCFs in Taiwan. PARTICIPANTS:
      Participants were 233 LTCF residents. MEASUREMENTS: Barthel index (BI), Charlson
      comorbidity index (CCI), hemoglobin A1c, episodes of LTCF-acquired pneumonia.
      INTERVENTION: None. RESULTS: A total of 233 residents (76.9 +/- 10.6 years, 54.9%
      males, 27.9% diabetic) from 10 private LTCFs participated. There were 173 LTCF
      acquired pneumonia episodes. The incidence of LTCF-acquired pneumonia between
      patients with and without diabetes, or between diabetic subjects with different
      status of glycemic control was similar. Adjusted for baseline BI, CCI, feeding
      tube placement, and baseline serum albumin, DM was not a significant risk factor
      for LTCF-acquired pneumonia. Poorer glycemic control (HbA1c >7%) was not a
      significant risk factor for LTCF-acquired pneumonia in diabetic subjects.
      CONCLUSIONS: Tighter glycemic control did not protect diabetic LTCF residents
      from pneumonia. A prospective randomized controlled trial is needed to determine
      the optimal goal of glycemic control for LTCF residents.

PMID- 21194658
TI  - Validation of the Minimum Data Set in identifying hospitalization events and
      payment source.
AB  - OBJECTIVES: To evaluate the accuracy of the Minimum Data Set (MDS) in identifying
      hospitalization events and payment source among nursing home residents. RESEARCH
      DESIGN: The 2003 MDS, Medicare Provider Analysis and Review File (MedPAR),
      Medicare denominator file, Medicaid Analytical Extract (MAX) long-term care file,
      and MAX personal summary file for 4 states (California, Ohio, New York, and
      Texas) were obtained and merged. SETTING: All Medicare/Medicaid-certified nursing
      ho-mes in these 4 states during 2003. PARTICIPANTS: All nursing home residents
      who were eligible for Medicare. Medicare or Medicaid managed care enrollees were
      excluded. MEASUREMENTS: Using the identification by linking the MDS and claims
      data as the "gold standard," we calculated false negative and false positive
      error rates of the MDS in identifying hospitalization events and payment source.
      RESULTS: As for the accuracy of the MDS in identifying hospitalization events,
      the false negative error rates ranged from 6.8% to 19.5% and the false positive
      error rates were between 12.0% and 15.7%, depending on the state. With regard to
      the identification of Medicare payment source, the MDS had a low false negative
      rate (varying from 0.4% to 1.1%), and a relatively high false positive rate
      (ranging from 6.1% to 14.9%). The MDS alone did not seem to be a sufficient
      source for identification of Medicaid payment source (false negative rate ranging
      from 11.0% to 55.3%). CONCLUSIONS: The accuracy of the MDS in identifying
      hospitalizations and payment sources varies across the study states, and should
      be evaluated carefully with regard to the intended uses of the data.

PMID- 21194659
TI  - Hypertension treatment and outcomes in US nursing homes: results from the US
      National Nursing Home Survey.
AB  - OBJECTIVES: The objective of this study was to describe antihypertensive
      medication use, determine what effects comorbid illness has on prescribing of
      commonly used antihypertensive medications, and explore how treatment affected
      selected clinical and functional outcomes in US nursing home residents. DESIGN:
      Cross-sectional observational study using data from the 2004 National Nursing
      Home Survey, a nationally representative sample of US nursing home residents.
      RESULTS: More than one half, 53.8%, of all residents had hypertension as a
      primary admission or current diagnosis. A large majority (84%) of residents with
      the diagnosis of hypertension were receiving at least one legend medication
      indicated for hypertension. The most common selection of pharmacologic agent was
      monotherapy with diuretics in 11% of all residents receiving antihypertensive
      medications. Hypertensive residents with a diagnosis of arrhythmia (odds ratio
      [OR] = 1.19, 95% confidence interval [CI] = 1.02-1.38), stroke (OR = 1.18, 95% CI
      = 1.05-1.34), or heart failure (OR = 1.17, 95% CI = 1.04-1.32) were more likely
      to be receiving a beta blocker. Those with diabetes (OR = 0.86, 95% CI = 0.77
      0.96), depression (OR = 0.78, 95% CI = 0.70-0.87), constipation (OR = 0.72, 95%
      CI = 0.61-0.84), or asthma (OR = 0.51, 95% CI = 0.34-0.74) were less likely to be
      receiving a beta blocker. Hospital admission was less likely (OR = 0.50, 95% CI =
      0.36-0.69) when residents were taking any commonly used antihypertensive
      medication (diuretics, beta blockers, angiotensin-converting enzyme/angiotensin
      receptor blockers [ACE/ARBs], calcium channel blockers, or alpha-blockers) but
      significantly more likely when therapy included a beta blocker (OR = 1.45, 95% CI
      = 1.18 - 1.78). Beta blockers were associated with an increased likelihood of
      falls (OR = 1.14, 95% CI = 1.04-1.27) and a decreased likelihood of constipation
      (OR 0.72, 95% CI = 0.61-0.84). Beta blockers were associated with a decreased
      likelihood of depression (OR 0.83, 95% CI = 0.74-0.92) as was the use of any
      commonly used antihypertensive (OR = 0.76, 95% CI = 0.63-0.90). CONCLUSION:
      Hypertension is prevalent in US nursing home residents and most residents with
      that diagnosis (84%) are being treated with antihypertensive medication. Through
      examination of the National Nursing Home Survey database, associations between
      the use of selected antihypertensive medication, comorbid illness, and specified
      outcomes were observed.

PMID- 21194660
TI  - Improving adherence with the use of hip protectors among older people living in
      nursing care facilities: a cluster randomized trial.
AB  - OBJECTIVES: To test different adherent strategies aimed at improving hip
      protector use among nursing care facility residents. DESIGN, SETTING AND
      PARTICIPANTS: A cluster randomized controlled trial with 234 residents older than
      75 years from 9 units of 7 nursing care facilities in the Northern Sydney region,
      Australia. INTERVENTION: Residents were cluster randomized in 3 groups. The first
      group received hard shell hip protectors without cost (no cost group). The second
      group received an educational session, a demonstration of the use of hip
      protectors, and free choice of type of hip protectors without cost (combined
      group). The third group was the control group who received a brochure about hip
      protectors. MEASUREMENTS: Primary outcome was adherence with the use of hip
      protectors at 3 and 6 months after recruitment. Secondary outcomes were falls,
      injuries, and fractures. RESULTS: No participants in the control group purchased
      hip protectors at any stage. At 3 months, 33% of participants in the no cost
      group and 27% in the combined group wore a hip protector at the time of visit.
      This declined to 25% and 24% respectively at 6 months. No significant difference
      was seen in any of the 3 adherence outcomes between the 2 intervention groups.
      The number of falls or hospitalizations did not differ between groups, with 5 hip
      fractures reported during the intervention period. Residents were more likely to
      be adherent if they were female and had greater restriction in daily activities.
      CONCLUSION: Providing free hip protectors to older people living in nursing care
      facilities was necessary to increase initial acceptance and adherence.
      Nevertheless, after 6 months the achieved level of adherence was not high enough
      to be associated with a reduction of hip fractures. The provision of educational
      sessions and demonstrations to nursing staff and participants had no added value
      in this trial.

PMID- 21194661
TI  - The relationship of vitamin D status to cardiovascular risk factors and
      amputation risk in veterans with peripheral arterial disease.
AB  - OBJECTIVES: Peripheral arterial disease (PAD) is a common and often overlooked
      entity responsible for considerable morbidity and mortality. Recent evidence
      suggests that nontraditional risk factors such as vitamin D may contribute to
      atherosclerosis. We hypothesized that vitamin D status was associated with
      cardiovascular risk factors and that vitamin D deficiency (25(OH)D <20 ng/mL)
      enhanced the risk of amputation. DESIGN: We reviewed medical records of 1435
      veterans between 2000 and 2008 in Tennessee via retrospective chart analysis
      using correlations, logistic regressions, t tests, and chi(2) analyses. RESULTS:
      Vitamin D status was significantly and inversely correlated with body mass index
      (BMI), glucose, and triglyceride values. Hypertension and diabetes but not
      smoking also emerged as significantly associated. Of the sample population, 5.2%
      (n = 75) had an amputation performed. Those individuals who were vitamin D
      deficient had a significantly higher amputation rate (6.7%) compared with
      patients who were nondeficient (4.2%). BMI, triglyceride, total cholesterol,
      hypertension, and diabetes were found to account for 5.7% of the variation in
      amputation status. Vitamin D concentration and deficiency status accounted for a
      nonsignificant amount of additional variance. CONCLUSIONS: We conclude that
      vitamin D deficiency is closely linked to increased adiposity, triglyceride, and
      glucose measurements. Vitamin D deficiency was associated with an increased
      amputation risk in veterans with PAD and appears to mediate its effects through
      traditional risk factors.

PMID- 21194662
TI  - Phase II study of the novel peptide-nucleic acid OHR118 in the management of
      cancer-related anorexia/cachexia.
AB  - BACKGROUND AND OBJECTIVE: OHR118 represents a new class of immunomodulatory and
      cytoprotective drugs in managing anorexia cachexia. Previously in patients with
      advanced HIV-AIDS, increases in appetite, strength, and alertness were noted. The
      objective was to determine the effect of OHR118 on appetite, early satiety, and
      nutritional intake in patients with advanced cancer. Secondary end points
      included changes in performance status, lean muscle mass, and quality of life
      (QOL). METHODS: Eligible patients received 4.0 mL of OHR118 in subcutaneous daily
      injections. Patients underwent bi-monthly evaluations during the 28-day initial
      treatment (phase A). Evaluations included Karnofsky performance status, Edmonton
      Symptoms Assessment Scale (ESAS), Patient-Generated Subjective Global Assessment
      (PG-SGA), Simmonds Functional Assessment (SFA), Dyspepsia Symptom Severity Index
      (DSSI), weight, lean body mass, skin fold thickness, and grip strength. Patients
      who benefited from phase A could elect to continue with therapy (phase B).
      RESULTS: Of 21 enrolled patients, 11 completed phase A. Eight patients chose to
      continue with OHR118 treatment (phase B). Weight stabilization or gain was
      observed in 7 of 11 patients. Total PG-SGA scores improved significantly (P <=
      .01). Appetite (P <= .01) and depression (P = .05) scores improved on ESAS.
      Frequent burping/belching (P = .02), feeling full (P = .04), and stomach
      distention (P = .03) improved on the DSSI. A deterioration in the timed sit to
      stand was noted (P = .01). OHR118 was well tolerated with no serious side effects
      reported. CONCLUSIONS: OHR118 again mediated statistically significant
      improvements in anorexia, dyspepsia, strength, and depression in this trial,
      consonant with the previous AIDS trial results.

PMID- 21194663
TI  - The importance of physician presence in nursing homes for residents with dementia
      and pneumonia.
AB  - OBJECTIVE: To study whether physician presence in the nursing home is related to
      clinical decision making, certainty, and honoring care preferences for patients
      with dementia and pneumonia. DESIGN: Cross-sectional survey of physicians.
      SETTING: Nursing homes in the United States and the Netherlands. PARTICIPANTS:
      Twenty-four US and 38 Dutch physicians who provide care for nursing home
      patients. MEASUREMENTS: Physicians reported their presence in the nursing home,
      diagnostic and treatment decisions for patients with dementia who had pneumonia,
      certainty about the diagnosis and patient and family preferences, and the extent
      to which they honored these preferences. These variables were examined in
      reference to physician presence in the nursing home. RESULTS: Physicians with
      higher nursing home presence were less likely to order a chest x-ray and to
      hospitalize patients with dementia and pneumonia, although this difference was
      not significant when adjusted for country. They also were more likely to be
      certain of family preferences, a difference that held even when adjusted for the
      strong confounder of country. CONCLUSION: Physician presence in the nursing home
      relates to some treatment decisions for patients with dementia and pneumonia.
      Policies that affect physician presence may change health care practices and
      related costs. Future studies should more closely examine how physicians use
      their time so as to better understand the importance of presence and what the US
      health care system might learn from the Dutch system.

PMID- 21194665
TI  - Comment on Beyond CMS quality measure adjustments.

PMID- 21194666
TI  - CAM, Religion, and Schrodinger's one mind.

PMID- 21194667
TI  - Trends that will affect your future ... a portrait of American societal health.
AB  - The SchwartzReport tracks emerging trends that will affect the world,
      particularly the United States. For EXPLORE, it focuses on matters of health in
      the broadest sense of that term, including medical issues, changes in the
      biosphere, technology, and policy considerations, all of which will shape our
      culture and our lives.

PMID- 21194668
TI  - Energy healers: who they are and what they do.
AB  - This paper surveys the landscape of energy healing, offering a taxonomy and
      conceptual overview of the work of practitioners. First, systems of energy
      healing are classified under four categories: an East Asian tradition, a Western
      professional tradition, a bioenergy tradition, and a contemporary metaphysical
      tradition. Examples of each are provided. Second, the possibility of core
      concepts in energy healing is broached, focusing specifically on five issues: the
      source of healing and its pathway of transmission, what it is that is being
      transmitted, what it is that healers do, the healer's state of consciousness, and
      requirements of clients in order to receive healing. Third, a discussion is
      provided of the relative importance of technique in energy healing. Fourth, what
      really matters for healing is proposed, emphasizing three factors: focus,
      intention, and compassion. Finally, the paper concludes by suggesting that
      formally trained energy practitioners do not have a monopoly on energy healing.

PMID- 21194669
TI  - Effects of a brief, comprehensive, yoga-based program on quality of life and
      biometric measures in an employee population: a pilot study.
AB  - OBJECTIVE: The aim of this study was to determine whether a comprehensive, yoga
      based wellness program could positively affect multiple markers of health and
      wellness in an employee population. DESIGN: Self-selected employees who enrolled
      in a new wellness class were invited to participate in a yoga-based wellness
      program. Participants met six days per week (Monday through Saturday) at 5:10 am.
      Sessions lasted for at least one hour, and the program was six weeks long. Each
      session consisted of power yoga interwoven with philosophical concepts and
      instruction about the benefits of mindfulness, breath, and meditation. Certain
      classes each week incorporated large and small group sharing, journal writing,
      and mindful eating exercises. Main outcome measures were biometric measures
      (height, weight, blood pressure, flexibility, body fat) and quality-of-life
      measures (physical, emotional, and spiritual well-being). RESULTS: Fifty-nine
      employees were invited to join the program; 50 consented to participate, of which
      37 (74%) attended more than 90% of classes. Participant age ranged from 24 to 76
      years. Statistically significant improvements were observed in weight (-4.84 +/-
      5.24 kg; P < .001), diastolic blood pressure (-2.66 +/- 8.31 mm/Hg; P = .03),
      flexibility score (relative change 11% +/- 20.92; P <.001), body fat percentage (
      1.94 +/- 2.68; P < .001), and overall quality of life (linear analog self
      assessment [LASA] score 3.73 +/- 8.11; P = .03). CONCLUSIONS: This pilot study
      suggests that a yoga-based, comprehensive wellness program is both feasible and
      efficacious in creating positive, short-term improvements in multiple domains of
      health and wellness for a population of employees.

PMID- 21194670
TI  - Integrative health coaching: an organizational case study.
AB  - OBJECTIVE: The aim of this study was to describe integrative health (IH) coaching
      as developed in three different interventions offered through a major medical
      center, as a step toward further defining the field of health coaching. STUDY
      DESIGN: An organizational case study was conducted with document analysis and
      interviews. SETTING/PARTICIPANTS: Interviewees were the first six IH coaches at
      Duke Integrative Medicine who provided 360 clients with individual and/or group
      coaching (two to 28 sessions) in a randomized clinical study and two work-site
      wellness programs. ANALYSIS: Qualitative analysis using the constant comparative
      method was conducted. RESULTS: Integrative health coaching is characterized by a
      process of self-discovery that informs goal setting and builds internal
      motivation by linking clients' goals to their values and sense of purpose. Time,
      commitment, and motivation are necessary in the IH coaching process. CONCLUSIONS:
      The underpinnings of IH coaching are distinct from the medical model, and the
      process is distinct from health education, executive coaching, and psychotherapy.
      Integrative health coaching fits well with the assumptions of integrative
      medicine and has a role in supporting behavior change.

PMID- 21194671
TI  - Meta-analysis: traditional Chinese medicine for improving immune response in
      patients with unresectable hepatocellular carcinoma after transcatheter arterial
      chemoembolization.
AB  - OBJECTIVE: The aim of this study was to evaluate whether Traditional Chinese
      Medicine (TCM) improves immune response for unresectable hepatocellular carcinoma
      (UHCC) after transcatheter arterial chemoembolization (TACE) by using meta
      analysis of data from the literature involving available randomized controlled
      trials of TCM in combination with TACE compared with that of TACE alone. METHODS:
      Literature retrieval was conducted through the Cochrane Library, MEDLINE,
      CENTRAL, Embase, CBMdisc, and CNKI, without language limitations. RESULTS: Based
      on our search criteria, we found 12 trials involving 1,008 patients. Our results
      showed that the differences of pooled weighted mean difference before and after
      treatment and 95% confidence intervals (CIs) were 13.63 (8.96-18.69; P = .0001)
      for the proportion of CD3(+) T cells, 10.56 (6.91-14.21; P = .0001) for the
      proportion of CD4(+) T cells, -3.40 (-6.83 to 0.03; P = .052) for the proportion
      of CD8(+) T cells, 0.54 (0.42-0.66; P = .0001) for the ratio of CD4(+)/CD8(+),
      and 12.34 (7.26-17.41; P = .0001) for the proportion of natural killer cells. No
      serious adverse events were reported. CONCLUSIONS: Traditional Chinese Medicine
      in combination with TACE improves the immune response of patients with UHCC.
      However, considering the strength of the evidence, additional randomized
      controlled trials are needed before TCM plus TACE can be recommended routinely.

PMID- 21194673
TI  - Cochrane CAM reviews commentary: is there more to quality than the research
      method itself?
AB  - The Cochrane Complementary Medicine Field is the group within the Cochrane
      Collaboration focused on facilitating the conduct of Cochrane systematic reviews
      of CAM therapies. The CAM Field represents an international collaborative effort
      among researchers, clinicians, consumers, and CAM practitioners from nearly every
      continent. The Field's central office is located at the Center for Integrative
      Medicine, University of Maryland School of Medicine, 520 W. Lombard St.,
      Baltimore, MD 21201. For more information, contact Eric Manheimer at:
      emanheimer@compmed.umm.edu. The Complementary Medicine Field is supported by
      Grant R24 AT001293 from the National Center for Complementary and Alternative
      Medicine (NCCAM). The contents of this article are solely the responsibility of
      the author and do not necessarily represent the official views of the NCCAM, or
      the National Institutes of Health.

PMID- 21194672
TI  - New insights on therapeutic touch: a discussion of experimental methodology and
      design that resulted in significant effects on normal human cells and
      osteosarcoma.
AB  - Our purpose is to discuss the study design and innovative approaches that led to
      finding significant effects of one energy medicine therapy, Therapeutic Touch
      (TT), on cells. In the original published studies, TT was shown to significantly
      increase human osteoblast DNA synthesis, differentiation, and mineralization;
      increase in a dose-dependent manner the growth of other human cell types; and
      decrease the differentiation and mineralization of a human osteosarcoma-derived
      cell line. A unique feature of the study's methodology and design that
      contributed to the success of the findings was that a basic level of skill and
      maturity of the TT practitioner was quantified for producing observable and
      replicable outcomes in a test administered to all TT practitioners. Only those
      practitioners that passed the test were selected for the study. (2) The
      practitioners were required to keep a journal, which appeared to promote their
      ability to stay centered and replicate their treatments over months of cell
      experimentation. (3) The origin of the cells that the practitioners were treating
      was explained to them, although they were blinded to cell type during the
      experiments. (4) Only early passage cells were used to maintain a stable cell
      phenotype. (5) Standard protocols for performing TT in the room were followed to
      ensure reproducible conditions. (6) Placebo controls and untreated controls were
      used for each experiment. (7) The principal investigator and technicians
      performing the assays were blinded as to the experimental groups, and all assays
      and procedures were well established in the laboratory prior to the start of the
      TT experiments. The absence of studies on the human biofield from mainstream
      scientific literature is also discussed by describing the difficulties
      encountered in publishing. These roadblocks contribute to our lack of
      understanding of the human biofield and energy medicine modalities in science. In
      conclusion, this report seeks to encourage well-designed, evidence-based studies
      on the human biofield and the therapeutic potential of the human biofield.

PMID- 21194674
TI  - Applying functional nutrition for chronic disease prevention and management:
      bridging nutrition and functional medicine in 21st century healthcare.

PMID- 21194675
TI  - A clinical scoring system for selection of patients for PTEN mutation testing is
      proposed on the basis of a prospective study of 3042 probands.
AB  - Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome are allelic, defined
      by germline PTEN mutations, and collectively referred to as PTEN hamartoma tumor
      syndrome. To date, there are no existing criteria based on large prospective
      patient cohorts to select patients for PTEN mutation testing. To address these
      issues, we conducted a multicenter prospective study in which 3042 probands
      satisfying relaxed CS clinical criteria were accrued. PTEN mutation scanning,
      including promoter and large deletion analysis, was performed for all subjects.
      Pathogenic mutations were identified in 290 individuals (9.5%). To evaluate
      clinical phenotype and PTEN genotype against protein expression, we performed
      immunoblotting (PTEN, P-AKT1, P-MAPK1/2) for a patient subset (n = 423). In order
      to obtain an individualized estimation of pretest probability of germline PTEN
      mutation, we developed an optimized clinical practice model to identify adult and
      pediatric patients. For adults, a semiquantitative score-the Cleveland Clinic
      (CC) score-resulted in a well-calibrated estimation of pretest probability of
      PTEN status. Overall, decreased PTEN protein expression correlated with PTEN
      mutation status; decreasing PTEN protein expression correlated with increasing CC
      score (p < 0.001), but not with the National Comprehensive Cancer Network (NCCN)
      criteria (p = 0.11). For pediatric patients, we identified highly sensitive
      criteria to guide PTEN mutation testing, with phenotypic features distinct from
      the adult setting. Our model improved sensitivity and positive predictive value
      for germline PTEN mutation relative to the NCCN 2010 criteria in both cohorts. We
      present the first evidence-based clinical practice model to select patients for
      genetics referral and PTEN mutation testing, further supported biologically by
      protein correlation.

PMID- 21194677
TI  - Identification of a systemic lupus erythematosus susceptibility locus at 11p13
      between PDHX and CD44 in a multiethnic study.
AB  - Systemic lupus erythematosus (SLE) is considered to be the prototypic autoimmune
      disease, with a complex genetic architecture influenced by environmental factors.
      We sought to replicate a putative association at 11p13 not yet exceeding genome
      wide significance (p < 5 * 10(-8)) identified in a genome-wide association study
      (GWAS). Our GWA scan identified two intergenic SNPs located between PDHX and CD44
      showing suggestive evidence of association with SLE in cases of European descent
      (rs2732552, p = 0.004, odds ratio [OR] = 0.78; rs387619, p = 0.003, OR = 0.78).
      The replication cohort consisted of >15,000 subjects, including 3562 SLE cases
      and 3491 controls of European ancestry, 1527 cases and 1811 controls of African
      American (AA) descent, and 1265 cases and 1260 controls of Asian origin. We
      observed robust association at both rs2732552 (p = 9.03 * 10(-8), OR = 0.83) and
      rs387619 (p = 7.7 * 10(-7), OR = 0.83) in the European samples with p(meta) =
      1.82 * 10(-9) for rs2732552. The AA and Asian SLE cases also demonstrated
      association at rs2732552 (p = 5 * 10(-3), OR = 0.81 and p = 4.3 * 10(-4), OR =
      0.80, respectively). A meta-analysis of rs2732552 for all racial and ethnic
      groups studied produced p(meta) = 2.36 * 10(-13). This locus contains multiple
      regulatory sites that could potentially affect expression and functions of CD44,
      a cell-surface glycoprotein influencing immunologic, inflammatory, and oncologic
      phenotypes, or PDHX, a subunit of the pyruvate dehydrogenase complex.

PMID- 21194678
TI  - SMOC1 is essential for ocular and limb development in humans and mice.
AB  - Microphthalmia with limb anomalies (MLA) is a rare autosomal-recessive disorder,
      presenting with anophthalmia or microphthalmia and hand and/or foot malformation.
      We mapped the MLA locus to 14q24 and successfully identified three homozygous
      (one nonsense and two splice site) mutations in the SPARC (secreted protein
      acidic and rich in cysteine)-related modular calcium binding 1 (SMOC1) in three
      families. Smoc1 is expressed in the developing optic stalk, ventral optic cup,
      and limbs of mouse embryos. Smoc1 null mice recapitulated MLA phenotypes,
      including aplasia or hypoplasia of optic nerves, hypoplastic fibula and bowed
      tibia, and syndactyly in limbs. A thinned and irregular ganglion cell layer and
      atrophy of the anteroventral part of the retina were also observed. Soft tissue
      syndactyly, resulting from inhibited apoptosis, was related to disturbed
      expression of genes involved in BMP signaling in the interdigital mesenchyme. Our
      findings indicate that SMOC1/Smoc1 is essential for ocular and limb development
      in both humans and mice.

PMID- 21194679
TI  - Targeted high-throughput sequencing identifies mutations in atlastin-1 as a cause
      of hereditary sensory neuropathy type I.
AB  - Hereditary sensory neuropathy type I (HSN I) is an axonal form of autosomal
      dominant hereditary motor and sensory neuropathy distinguished by prominent
      sensory loss that leads to painless injuries. Unrecognized, these can result in
      delayed wound healing and osteomyelitis, necessitating distal amputations. To
      elucidate the genetic basis of an HSN I subtype in a family in which mutations in
      the few known HSN I genes had been excluded, we employed massive parallel exon
      sequencing of the 14.3 Mb disease interval on chromosome 14q. We detected a
      missense mutation (c.1065C>A, p.Asn355Lys) in atlastin-1 (ATL1), a gene that is
      known to be mutated in early-onset hereditary spastic paraplegia SPG3A and that
      encodes the large dynamin-related GTPase atlastin-1. The mutant protein exhibited
      reduced GTPase activity and prominently disrupted ER network morphology when
      expressed in COS7 cells, strongly supporting pathogenicity. An expanded screen in
      115 additional HSN I patients identified two further dominant ATL1 mutations
      (c.196G>C [p.Glu66Gln] and c.976 delG [p.Val326TrpfsX8]). This study highlights
      an unexpected major role for atlastin-1 in the function of sensory neurons and
      identifies HSN I and SPG3A as allelic disorders.

PMID- 21194681
TI  - Characterization of mandibular movement during speech in the presence of oral
      articulatory perturbation.
AB  - OBJECTIVE: Mandibular movement is essential for speech, swallowing, and
      mastication. The purpose of this study was to test the hypothesis that altering
      oral cavity geometry would result in an increased vertical and more posterior jaw
      displacement during speech. DESIGN: Twelve English speaking female adult dentate
      volunteers, age range 21-31 (mean +/- SD age, 25.3 +/- 2.2 years) participated in
      this prospective crossover study. Compensatory jaw movement was measured during
      pronunciation of the sound "s" in three vowel contexts (/i/, /a/, /u/). An
      acrylic palatal device was used to perturb the oral cavity in anterior and
      posterior palate. Speech was recorded under five conditions; no device, device,
      device after 15 min, device after 2 weeks, after removal of the device. The
      vertical, horizontal, and lateral mandibular movement was recorded. A Within
      Subject 2-Factorial Repeated Measures ANOVA was performed to evaluate the
      statistical significance (p <= 0.05). RESULTS: The repeated measures for the mean
      vertical displacement revealed a main effect for the condition [F (6.970),
      p=.001], and the device [F (13.634), p=.001]. For horizontal displacement there
      was a main effect for the condition [F (6.970), p=.001], and the device [F
      (13.634), p=.001]. For lateral displacement there was a main effect for the
      device [F (3.790), p=.051]. CONCLUSIONS: Our study demonstrated that during the
      pronunciation of "s" the jaw position is extremely stable, even when the oral
      cavity geometry is altered. Therefore, compensation for the perturbation occurs
      using other speech articulators such as the tongue.

PMID- 21194676
TI  - Meta-analysis of Dense Genecentric Association Studies Reveals Common and
      Uncommon Variants Associated with Height.
AB  - Height is a classic complex trait with common variants in a growing list of genes
      known to contribute to the phenotype. Using a genecentric genotyping array
      targeted toward cardiovascular-related loci, comprising 49,320 SNPs across
      approximately 2000 loci, we evaluated the association of common and uncommon SNPs
      with adult height in 114,223 individuals from 47 studies and six ethnicities. A
      total of 64 loci contained a SNP associated with height at array-wide
      significance (p < 2.4 * 10(-6)), with 42 loci surpassing the conventional genome
      wide significance threshold (p < 5 * 10(-8)). Common variants with minor allele
      frequencies greater than 5% were observed to be associated with height in 37
      previously reported loci. In individuals of European ancestry, uncommon SNPs in
      IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide
      genotyping arrays, were strongly associated with height (p < 3 * 10(-11)).
      Conditional analysis within associated regions revealed five additional variants
      associated with height independent of lead SNPs within the locus, suggesting
      allelic heterogeneity. Although underpowered to replicate findings from
      individuals of European ancestry, the direction of effect of associated variants
      was largely consistent in African American, South Asian, and Hispanic
      populations. Overall, we show that dense coverage of genes for uncommon SNPs,
      coupled with large-scale meta-analysis, can successfully identify additional
      variants associated with a common complex trait.

PMID- 21194680
TI  - Mutations in the SPARC-related modular calcium-binding protein 1 gene, SMOC1,
      cause waardenburg anophthalmia syndrome.
AB  - Waardenburg anophthalmia syndrome, also known as microphthalmia with limb
      anomalies, ophthalmoacromelic syndrome, and anophthalmia-syndactyly, is a rare
      autosomal-recessive developmental disorder that has been mapped to 10p11.23. Here
      we show that this disease is heterogeneous by reporting on a consanguineous
      family, not linked to the 10p11.23 locus, whose two affected children have a
      homozygous mutation in SMOC1. Knockdown experiments of the zebrafish smoc1
      revealed that smoc1 is important in eye development and that it is expressed in
      many organs, including brain and somites.

PMID- 21194683
TI  - Attentional asymmetry or laterality of motor control? Commentary on Buckingham et
      al. (this issue).

PMID- 21194682
TI  - Studies on the cationization of agarose.
AB  - Cationized agaroses with different degrees of substitution (0.04-0.77) were
      synthesized, employing 3-chloro-2-hydroxypropyltrimethylammonium chloride
      (CHPTAC). The influence of different reaction parameters on the substitution
      degree and molecular weight was evaluated. The investigated parameters were
      concentration of reagents, temperature, time, and addition of NaBH(4). The
      products were characterized by means of scanning electronic microscopy, infrared
      spectroscopy, viscosimetry, and NMR spectroscopy. Methanolysis products were
      studied by electrospray ionization mass spectrometry. The higher the
      concentration of CHPTAC employed, a higher degree of substitution was obtained,
      if the optimum concentration of NaOH in each case was employed. Insufficient
      quantities of NaOH reduced epoxide formation and the reacting alkoxides of the
      polysaccharide, whereas an excess of NaOH favored degradation of the epoxide and
      decrease in the molecular weight of the product. A reaction time of 2h was
      sufficient to obtain products with the maximum degree of substitution for each
      case. The addition of NaBH(4) gave products with a slightly higher molecular
      weight, but the extra cost involved should not justify its use for large-scale
      application.

PMID- 21194684
TI  - Anosognosia for hemiplegia with preserved awareness of complete cortical
      blindness following intracranial hemorrhage.
AB  - A 51-year-old woman presented with anosognosia for hemiplegia (AHP), neglect, and
      a complete loss of vision, for which she was almost immediately aware.
      Neuroimaging studies revealed intracranial hemorrhages in the medial temporal
      lobes bilaterally, extending back to the occipital cortex, but sparing the
      calcarine cortex. A large right frontal-parietal hemorrhage which extended to the
      posterior body of the corpus callosum was also observed. The patient's vision
      slowly improved, and by 11 months post onset, formal visual fields revealed
      improvement primarily in the left upper quadrants only. In contrast, resolution
      of her AHP occurred between the 26th and 31st day post onset. Awareness of motor
      impairment was correlated with her ability to initiate finger tapping in her left
      hemiplegic/paretic hand. During the time she was unaware of her motor deficits
      but aware of her visual impairments, her dreams did not reflect concerns over
      visual or motor limitations. The findings support a "modular" theory of
      anosognosia.

PMID- 21194685
TI  - [Fibrosing colonopathy, an increasing complication of cystic fibrosis].

PMID- 21194686
TI  - [Role of the virus in the etiology of respiratory pictures].

PMID- 21194687
TI  - Metformin improves semen characteristics of oligo-terato-asthenozoospermic men
      with metabolic syndrome.
AB  - To examine the appropriate treatment of oligo-terato-asthenozoospermic patients
      with metabolic syndrome, 45 patients were treated with metformin for 6 months.
      The use of metformin was associated with a statistically significant reduction in
      insulin resistance and sex hormone-binding globulin levels, a statistically
      significant increase in serum androgen levels, and a consequent improvement in
      semen characteristics.

PMID- 21194688
TI  - Real-time random delay compensation with prediction-based digital redesign.
AB  - Today's technological demands require challenging control solutions such as real
      time applications of Networked Control System (NCS). However, due to
      communication protocol and shared data bus, NCS experiences uncertain and
      unpredictable time delays in both input and output channels. These delays cause
      asynchronization between the controller and the plant thereby degrading the
      performance of closed-loop control systems. To address this problem, this paper
      proposes to utilize digital redesign technique to provide real-time random delay
      compensation.

PMID- 21194689
TI  - Hospitalisations and deaths due to unintentional cutting or piercing injuries at
      home amongst young and middle-aged New Zealanders.
AB  - AIMS: To describe the incidence and characteristics of unintentional cutting or
      piercing injuries at home resulting in death or hospital inpatient treatment
      amongst young and middle-aged New Zealanders. PATIENTS AND METHODS: Inpatient
      admissions amongst individuals aged 20-64 years with a primary diagnosis of
      cutting or piercing injury (ICD-9AM E code: E920, and ICD-10-AM E codes: W25-29,
      W45)and a length of stay of 24 h or more, were identified using the national
      morbidity (1997-2006) and mortality (1996-2005) databases compiled by the New
      Zealand Ministry of Health. Relevant data were extracted and analysed. RESULTS:
      During the 10-year period (1997-2006) 21,559 people aged 20-64 years had a
      primary admission to hospital for an injury caused by unintentional cutting or
      piercing, 29% (6355) of which occurred at home. The place of injury was not
      identified in a further 43% (9293) of records. During the 10-year period (1996
      2005) 25 people aged 20-64 years died of injuries of this nature, 18 of which
      occurred at home (in 2 cases the place of injury was not recorded). The
      hospitalisation rate following cutting or piercing at home was 24.9 per 100,000.
      For every death there were 352 admissions to hospital, with rates of admission
      almost two-fold greater amongst 20-24 year olds compared to those aged 60-64
      years. CONCLUSION: Almost 30% of unintentional cutting or piercing related
      injuries amongst young and middle aged adults occur at home. Whilst death is
      uncommon, the causes and preventability of the high numbers of hospitalisations,
      particularly amongst young adults, require research attention.

PMID- 21194690
TI  - Alcohol and psychoactive drugs increased the pre-hospital mortality in 655 fall
      related fatalities in Greece: a call for management protocols.
AB  - INTRODUCTION: The frequency of alcohol and psychoactive drugs in fall-related
      fatalities and their effect on type, severity of injury and location of death
      constitute the subjects of this study. METHODS: A retrospective analysis based on
      autopsy and toxicology compared demographics, location of injury; intention for
      the injury, height of fall, Abbreviated Injury Scale--90 (AIS-90), post-mortem
      Injury Severity Score (ISS), and location of death. RESULTS: Amongst 655 fall
      related fatalities screened for alcohol and psychoactive drugs 123 (18.8%) were
      classified in the positive toxicology group (PTG) and the remaining in the
      negative toxicology group (NTG). The median ages were 48 (16-94) years for the
      PTG and 62 (12-96) years for the NTG. The screened represent 31% of the national
      toll. The median height of fall was 7 m and the median blood alcohol
      concentration was 53 (1.5-630)mg/dl. Males were more likely to be included in the
      PTG than females (21.6 versus 13.6%; p = 0.014) as were the aged between 11 and
      60 years. The odds of severe (AIS >= 3) head, thoracic, abdominal, extremity, and
      spine injuries were not influenced by toxicology status. Fatalities of the PTG
      were as likely to have severe trauma (ISS >= 16) as were fatalities of the NTG
      (93.5 versus 90.8%; p = 0.34). There was no significant difference of ISS between
      PTG (median ISS 43, range: 6-75) and NTG (median ISS 35, range: 3-75).
      Nevertheless, 76.4% of the subjects of the PTG died during the pre-hospital stage
      of care compared to 60.5% of the subjects of the NTG, which was highly
      significant (or = 2.80, p = 0.001) after controlling for confounders as age,
      gender, intention for injury, height of fall, and ISS. CONCLUSIONS: In fall
      related trauma, alcohol and psychoactive drugs increased the risk of death during
      the pre-hospital stage by 2.80 times. This is strong evidence that specific
      protocols for their early management should be instituted.

PMID- 21194691
TI  - Guidelines for fracture healing assessments in clinical trials. Part I:
      definitions and endpoint committees.
AB  - Patients sustaining long bone fractures experience a significant socioeconomic
      burden. Investigational products are in developmental phases in an attempt to
      significantly reduce the time to fracture healing, however, high quality clinical
      trials need to be conducted in order to evaluate the efficacy of these
      interventions. The assessment of fracture healing is not a standardised process
      as it involves a degree of subjectivity. The use of endpoint Adjudication
      Committees to adjudicate fracture healing in clinical trials has the potential to
      help to resolve this issue. This manuscript outlines the current definitions used
      in the assessment of fracture healing and highlights the need for endpoint
      Adjudication Committees in fracture healing trials.

PMID- 21194692
TI  - Guidelines for fracture healing assessments in clinical trials. Part II:
      electronic data capture and image management systems--Global AdjudicatorTM
      system.
AB  - Adjudication of outcomes helps to reduce variation in outcome assessment when
      clinical judgement is used. Adjudication is extremely important when the outcome
      being measured is subjective, as in the assessment of fracture healing.
      Adjudication Committees have the potential to provide a systematic, independent,
      and unbiased method of determining fracture healing. In order to make the
      adjudication process less time consuming and more efficient, Global Research
      SolutionsTM, a Contract Research Organization which specialises in orthopaedic
      and surgical clinical trials, developed the Global AdjudicatorTM, a web-based
      system, to serve as both an image management system and electronic data capture
      system. This manuscript highlights the features of the Global AdjudicatorTM and
      demonstrates the benefits of using a web-based adjudication system.

PMID- 21194693
TI  - Effects of lycopene supplementation on oxidative stress and markers of
      endothelial function in healthy men.
AB  - OBJECTIVE: The objective was to determine the effects of lycopene supplementation
      on endothelial function assessed by reactive hyperemia peripheral arterial
      tonometry (RH-PAT) and oxidative stress. METHODS: Healthy men (n=126) were
      randomized to receive placebo (n=38), 6 mg (n=41), or 15 mg (n=37) lycopene daily
      for 8-week. RESULTS: Serum lycopene increased in a dose-dependent manner after 8
      week supplementation (P<0.001). The 15 mg/day group had greater increase in
      plasma SOD activity (P=0.014) and reduction in lymphocyte DNA comet tail length
      (P=0.042) than the placebo group. Intragroup comparison revealed a 23% increase
      in RH-PAT index from baseline (1.45+/-0.09 vs. 1.79+/-0.12; P=0.032) in the 15
      mg/day group after 8-week. hs-CRP, systolic blood pressure, sICAM-1 and sVCAM-1
      significantly decreased, and beta-carotene and LDL-particle size significantly
      increased only in the 15 mg/day group. Interestingly, the beneficial effect of
      lycopene supplementation on endothelial function (i.e., RH-PAT and sVCAM-1) were
      remarkable in subjects with relatively impaired endothelial cell function at
      initial level. Changes in RH-PAT index correlated with SOD activity (r=0.234,
      P=0.017) especially in the 15 mg lycopene/day group (r=0.485, P=0.003),
      lymphocyte DNA comet tail moment (r=-0.318, P=0.001), and hs-CRP (r=-0.238,
      P=0.011). In addition, changes in lycopene correlated with hs-CRP (r=-0.230,
      P=0.016) and SOD activity (r=0.205, P=0.037). CONCLUSION: An increase in serum
      lycopene after supplementation can reduce oxidative stress which may play a role
      in endothelial function.

PMID- 21194694
TI  - Evaluation of a flexible force sensor for measurement of helmet foam impact
      performance.
AB  - The association between translational head acceleration and concussion remains
      unclear and provides a weak predictive measure for this type of injury; thus,
      alternative methods of helmet evaluation are warranted. Recent finite element
      analysis studies suggest that better estimates of concussion risk can be obtained
      when regional parameters of the cranium, brain and surrounding tissues are
      included. Lacking, however, are empirical data at the head-helmet interface with
      regards to contact area and force. Hence, the purpose of this study was to
      evaluate a system to capture the impact force distribution of helmet foams.
      Thirteen Flexiforce((r)) sensors were arranged in a 5 * 5 cm array, secured to a
      load cell. Three densities of foam were repeatedly impacted with 5 J of energy
      during ambient (20 degrees C) and cold (-25 degrees C) conditions. RMS error,
      calculated relative to the global force registered by the load cell, was <1.5% of
      the measurement range during individual calibration of the Flexiforce((r))
      sensors. RMS error was 5% of the measured range for the global force estimated by
      the sensor array. Load distribution measurement revealed significant differences
      between repeated impacts of cold temperature foams for which acceleration results
      were non-significant. The sensor array, covering only 36% of the total area,
      possessed sufficient spatial and temporal resolution to capture dynamic load
      distribution patterns. Implementation of this force mapping system is not limited
      to helmet testing. Indeed it may be adopted to assess other body regions
      vulnerable to contact injuries (e.g., chest, hip and shin protectors).

PMID- 21194695
TI  - Apparent transverse compressive material properties of the digital flexor tendons
      and the median nerve in the carpal tunnel.
AB  - Carpal tunnel syndrome is a frequently encountered peripheral nerve disorder
      caused by mechanical insult to the median nerve, which may in part be a result of
      impingement by the adjacent digital flexor tendons. Realistic finite element (FE)
      analysis to determine contact stresses between the flexor tendons and median
      nerve depends upon the use of physiologically accurate material properties. To
      assess the transverse compressive properties of the digital flexor tendons and
      median nerve, these tissues from ten cadaveric forearm specimens were compressed
      transversely while under axial load. The experimental compression data were used
      in conjunction with an FE-based optimization routine to determine apparent
      hyperelastic coefficients (MU and alpha) for a first-order Ogden material
      property definition. The mean coefficient pairs were MU=35.3 kPa, alpha=8.5 for
      the superficial tendons, MU=39.4 kPa, alpha=9.2 for the deep tendons, MU=24.9
      kPa, alpha=10.9 for the flexor pollicis longus (FPL) tendon, and MU=12.9 kPa,
      alpha=6.5 for the median nerve. These mean Ogden coefficients indicate that the
      FPL tendon was more compliant at low strains than either the deep or superficial
      flexor tendons, and that there was no significant difference between superficial
      and deep flexor tendon compressive behavior. The median nerve was significantly
      more compliant than any of the flexor tendons. The material properties determined
      in this study can be used to better understand the functional mechanics of the
      carpal tunnel soft tissues and possible mechanisms of median nerve compressive
      insult, which may lead to the onset of carpal tunnel syndrome.

PMID- 21194696
TI  - Determination of quaternary ammonium compounds in seawater samples by solid-phase
      extraction and liquid chromatography-mass spectrometry.
AB  - A method for the simultaneous determination of two biocidal quaternary ammonium
      compounds; didecyldimethylammonium chloride (didecyldimethyl quat) and
      dodecylbenzyldimethylammonium chloride (benzyl quat), in seawater by solid phase
      extraction (SPE) followed by liquid chromatography-mass spectrometry (LC-MS) was
      developed. The optimised procedure utilised off-line extraction of the analytes
      from seawater using polymeric (Strata-X) SPE cartridges. Recoveries ranged from
      80 to 105%, with detection limits at the low parts-per-trillion (ng/l) level for
      both analytes. To demonstrate sensitivity, environmental concentrations were
      measured at three different locations along the North East coast of England with
      measured values in the range 120-270ng/l.

PMID- 21194697
TI  - Study of the enantiomeric separation of an acetamide intermediate by using
      supercritical fluid chromatography and several polysaccharide based chiral
      stationary phases.
AB  - Four chiral stationary phases, based on the phenylcarbamate derivatives of
      amylose or cellulose: Chiralcel OD-H, Chiralpak AD, Lux Cellulose-2 and Lux
      Amylose-2, were evaluated for the enantiomeric separation of an acetamide chiral
      intermediate, the (4S-trans)-4-(ethylamino)-4-(N-acetamide)-5,6-dihydro-(6S)
      methyl-4H-thieno-[2,3-b]thiopyran-7,7-dioxide, using SFC. The effect of the
      different modifiers and temperatures, on the separation, was also studied. The
      chiral separation could not be achieved using the Chiralpak AD column,
      nevertheless the other columns provided excellent results with analysis times
      close to 6 min and resolutions higher than 2. The highest enantioresolutions and
      retentions were obtained with the Lux Cellulose-2 column and 2-propanol as
      organic modifier. The isoelution temperatures were estimated from the van't Hoff
      plots, and in all the cases they were above the temperature range studied which
      means that the enantiomeric separation was enthalpy driven.

PMID- 21194698
TI  - Effect of monomer mixture composition on structure and chromatographic properties
      of poly(divinylbenzene-co-ethylvinylbenzene-co-2-hydroxyethyl methacrylate)
      monolithic rod columns for separation of small molecules.
AB  - Porous poly(divinylbenzene-co-ethylvinylbenzene-co-2-hydroxyethyl methacrylate)
      monoliths were synthesized via thermally initiated free-radical polymerization in
      confines of surface-vinylized glass columns (150 mm * 3 mm i.d.) and applied to
      the reversed-phase separation of low-molecular-weight aromatic compounds. In
      order to compensate for the polymer shrinkage during the synthesis and prevent
      the monolith from detachment from the column wall, polymerization was conducted
      under nitrogen pressure. The reaction proceeded at 60 degrees C for 22 h. 2,2'
      Azo-bis-isobutironitrile was used as the initiator and 1-dodecanol was used as
      the porogen. A series of monoliths with different monomer ratios were obtained.
      All the monoliths had high specific surface areas ranging from 370 to 490 m(2)/g.
      In the studied range of monomer mixture compositions, the mechanical stability of
      the stationary phase in water/acetonitrile eluents was found to be high enough
      and practically insensitive to the fraction of 2-hydroxyethyl methacrylate
      (HEMA). Increasing the molar fraction of HEMA from 10.5% to 14.7% resulted in the
      decrease of column permeability by two orders of magnitude (from 1.1*10(-12) to
      1.8*10(-14) m(2)) and led to weaker retention of alkylbenzenes. The higher HEMA
      content was shown to reduce the plate height of the columns in the separation of
      small molecules from 160-490 MUm to 40-76 MUm. This was attributed mainly to the
      decrease of the domain size of the monoliths leading to lower eddy dispersion and
      mass transfer resistance in the column.

PMID- 21194699
TI  - In vitro cytochrome P450 activity: development and validation of a sensitive high
      performance liquid chromatography-tandem mass spectrometry method for the
      quantification of six probe metabolites after derivatization with pyridine-3
      sulfonyl chloride in an aqueous environment.
AB  - For the determination of the in vitro cytochrome P450 activity in microsomes, a
      quantification method for the probe metabolites, formed during incubation, is
      required. Due to insufficient sensitivity of a previously developed high
      performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method
      for some of the metabolites, a fast and easy derivatization method with pyridine
      3-sulfonyl chloride (PS) is described. Acetaminophen (CYP1A2), dextrorphan
      (CYP2D6), hydroxy-chlorzoxazone (CYP2E1) and hydroxy-mephenytoin (CYP2C19) can be
      derivatized because of the presence of a phenolic OH, whereas hydroxy-midazolam
      (CYP3A4) and hydroxy-tolbutamide (CYP2C9) remain unchanged. As PS improves the
      ionization efficiency in the positive electrospray ionization (ESI) mode, the
      sensitivity of the detection is improved significantly and meets requirements for
      the activity determination. Native negative electrospray type molecules,
      moreover, become positive ESI candidates. The direct derivatization in the
      aqueous incubation medium, without any other sample pre-treatment steps, such as
      evaporation or extraction, makes this procedure easy to perform. The method using
      20s microwave irradiation was shown to equal a 10min reaction in a 60 degrees C
      heating block, consequently simplifying and shortening the process. Collision
      induced fragmentation of the derivatives resulted in at least one native
      compound, rather than derivative, specific product ion, thereby improving the
      selectivity of the method in the multiple reaction monitoring mode. The HPLC
      MS/MS method was validated, and was demonstrated to be sensitive, selective,
      precise and accurate. The absence of a relative matrix effect was established,
      notwithstanding that an absolute matrix effect was observed. The analysis of a
      sample after microsomal incubation, from which some of the metabolites could not
      be quantified using the method without derivatization, proved the usefulness of
      the method.

PMID- 21194700
TI  - Analyte migration in anisotropic nanostructured ultrathin-layer chromatography
      media.
AB  - We investigate the performance of highly anisotropic nanostructured thin film
      ultrathin-layer chromatography (UTLC) media with porosity and architecture
      engineered using the glancing-angle deposition (GLAD) process. Our anisotropic
      structures resemble nanoblades, producing channel-like features that partially
      decouple analyte migration from development direction, offering new separation
      behaviours. Here we study GLAD-UTLC plate performance in terms of migration
      distance, plate number, retention factor and a figure of merit specific to GLAD
      UTLC, track deviation angle. Migration distances increase with porosity by a
      factor of two for all feature orientations (up to a maximum of 22 mm) over the
      range of porosities considered in this study. Plate numbers approaching 1100 are
      observed for GLAD-UTLC plates when the nanoblade features are aligned with the
      development direction. We present a theoretical model describing mobile phase
      flow in anisotropic GLAD-UTLC media, and find good agreement with experimental
      results. Our plates provide channel features that reduce transverse spot
      broadening while providing the wide pores required for rapid migration and high
      separation performance. These improvements may enable a greater number of
      parallel separations on miniaturized GLAD-UTLC plate formats. Their small sizes
      should also make them compatible with the Office Chromatography concept in which
      office peripherals (inkjet printers and flatbed scanners) replace conventional
      TLC instruments. Equipped with a better understanding of the unique GLAD-UTLC
      elution behaviours, we expect to further improve performance in the future.

PMID- 21194701
TI  - A systematic investigation of algorithm impact in preparative chromatography with
      experimental verifications.
AB  - Computer-assisted optimization of chromatographic separations requires finding
      the numerical solution of the Equilibrium-Dispersive (ED) mass balance equation.
      Furthermore, the competitive adsorption isotherms needed for optimization are
      often estimated numerically using the inverse method that also solves the ED
      equations. This means that the accuracy of the estimated adsorption isotherm
      parameters explicitly depends on the numerical accuracy of the algorithm that is
      used to solve the ED equations. The fast and commonly used algorithm for this
      purpose, the Rouchon Finite Difference (RFD) algorithm, has often been reported
      not to be able to accurately solve the ED equations for all practical preparative
      experimental conditions, but its limitations has never been completely and
      systematically investigated. In this study, we thoroughly investigate three
      different algorithms used to solve the ED equations: the RFD algorithm, the
      Orthogonal Collocation on Finite Elements (OCFE) method and a Central Difference
      Method (CDM) algorithm, both for increased theoretical understanding and for real
      cases of industrial interest. We identified discrepancies between the
      conventional RFD algorithm and the more accurate OCFE and CDM algorithms for
      several conditions, such as low efficiency, increasing number of simulated
      components and components present at different concentrations. Given high enough
      efficiency, we experimentally demonstrate good prediction of experimental data of
      a quaternary separation problem using either algorithm, but better prediction
      using OCFE/CDM for a binary low efficiency separation problem or separations when
      the compounds have different efficiency. Our conclusion is to use the RFD
      algorithm with caution when such conditions are present and that the rule of
      thumb that the number of theoretical plates should be greater than 1000 for
      application of the RFD algorithm is underestimated in many cases.

PMID- 21194702
TI  - Isolation and purification of blood group antigens using immuno-affinity
      chromatography on short monolithic columns.
AB  - Monolithic columns have gained increasing attention as stationary phases for the
      separation of biomolecules and biopharmaceuticals. In the present work the
      performance of monolithic convective interaction media (CIM((r))) chromatography
      for the purification of blood group antigens was established. The proteins
      employed in this study are derived from blood group antigens Knops, JMH and
      Scianna, equipped both with a His-tag and with a V5-tag by which they can be
      purified. In a first step a monoclonal antibody directed against the V5-tag was
      immobilized on a CIM((r)) Disk with epoxy chemistry. After this, the immobilized
      CIM((r)) Disk was used in immuno-affinity chromatography to purify the three
      blood group antigens from cell culture supernatant. Up-scaling of the applied
      technology was carried out using CIM((r)) Tubes. In comparison to conventional
      affinity chromatography, blood group antigens were also purified via His-tag
      using a HiTrap((r)) metal-affinity column. The two purifications have been
      compared regarding purity, yield and purification speed. Using the monolithic
      support, it was possible to isolate the blood group antigens with a higher flow
      rate than using the conventional bed-packed column.

PMID- 21194703
TI  - Hydrogen-bonded layer-by-layer films of block copolymer micelles with pH
      responsive cores.
AB  - We report on construction of hydrogen-bonded monolayers and multilayers of
      micelles of the poly(2-(diethylamino)ethyl methacrylate)-block-poly(N-isopropyl
      acrylamide) (PDEA-b-PNIPAM) with PNIPAM-corona and polybasic PDEA cores. Films
      were constructed at pH 7.5 and 25 degrees C to assure the deposition of PDEA-b
      PNIPAM in the micellar form. When monolayers of block copolymer micelles (BCMs)
      were exposed to moderately acidic pH values, micellar cores dissolved, while PDEA
      b-PNIPAM remained adsorbed at the surface as unimers. In contrast to reversible
      micellization of PDEA-b-PNIPAM in solution, micelle-to-unimer transition was
      irreversible at the surface. Adsorption of a layer of tannic acid (TA) or
      polyethacrylic acid (PEAA) on top of BCM monolayers inhibited pH-triggered
      morphological changes within adsorbed BCMs. By taking advantage of the high pK(a)
      values of TA and PEAA, we were also able to construct multilayers of PDEA-b
      PNIPAM micelles through hydrogen bonding interactions between micellar PNIPAM
      coronas and TA or PEAA. Similar to BCM monolayers coated with TA or PEAA,
      dissolution of BCMs was also inhibited when incorporated within hydrogen-bonded
      multilayers. Such inhibition of dissolution is due to enhanced hydrogen bonding
      interactions between coronal PNIPAM chains and protonated TA molecules or PEAA
      chains at decreasing pH values restricting the pH-induced conformational changes
      of the micellar core chains within the adsorbed layer. Films of responsive BCMs
      are attractive coatings for controlled delivery of functional molecules from
      surfaces due to a combination of stimuli-response properties with the relatively
      high loading capacity for functional molecules.

PMID- 21194704
TI  - Preparation of polydiacetylene immobilized optically encoded beads.
AB  - Polydiacetylene (PDA), which can change the chromic and fluorescence properties
      by inducing environmental perturbations, is immobilized on planar solid supports
      for many biological applications. In this work, we immobilize PDA onto optically
      encoded spherical beads (PDA-SERS beads). The prepared PDA immobilized beads (36
      MUm) exhibit a blue color without fluorescence. By inducing stress, their color
      and fluorescence properties are changed to red with fluorescence. The SERS
      spectra of the PDA-SERS beads can be recognized over the PDA background.
      Moreover, our PDA immobilization methods are successfully applied to silica
      surface SERS-encoded beads (5 MUm) and proven to also be useful in fluorescence
      encoding systems.

PMID- 21194705
TI  - Comparison between measurements of elasticity and free amino group content of
      ovalbumin microcapsule membranes: discrimination of the cross-linking degree.
AB  - An inverse method is used to characterize the membrane mechanical behavior of
      liquid filled microcapsules. Cross-linked ovalbumin microcapsules are flowed and
      deformed into a cylindrical microchannel of comparable size. The deformed shape
      is compared to predictions obtained numerically when modeling a capsule under the
      same flow conditions. The unknown shear modulus value corresponds to the best
      fit. The degree of reticulation is estimated in parallel by determining the free
      amino groups remaining on the microcapsules after the cross-linking reaction. We
      characterize microcapsule populations fabricated at different reaction pH (5-8)
      and times (5-30 min) to study different cross-linking degrees. The capsule shear
      modulus and the amino groups are nearly constant with the reaction pH for the
      capsules fabricated after 5 min of reticulation. The shear modulus increases with
      the reaction time, while the NH(2) content decreases with it. A global increase
      in shear modulus with pH is also observed, together with an unexpected increase
      in NH(2) content. The study shows that the inverse method is capable of
      discriminating between various cross-linking degrees of microcapsules. Moreover,
      for this type of microcapsules, the mechanical method appears more reliable than
      the chemical one to obtain an estimation of their cross-linking degree.

PMID- 21194706
TI  - Role of added counterions in the micellar growth of bisquaternary ammonium halide
      surfactant (14-s-14): 1H NMR and viscometric studies.
AB  - The change in the morphology of a series of dicationic gemini surfactants
      C(14)H(29)(CH(3))(2)N(+)-(CH(2))(s)-N(+)(CH(3))(2)C(14)H(29), 2Br(-) (14-s-14;
      s=4-6) on their interaction with inorganic (KBr, KNO(3), KSCN) and organic salts
      (NaBenz, NaSal) have been thoroughly investigated by means of (1)H NMR spectral
      analysis and the results are well supported by viscosity measurements. The
      presence of salt counterions results in structural transition (spherical to
      nonspherical) of gemini micelles in aqueous solution. With an increase in salt
      concentration all the three gemini surfactants showed changes in their aggregate
      morphology. This change is dependent on the nature and size of the added
      counterion. The effect of inorganic counterions on the micellar growth is
      observed to follow the Hofmeister series (Br(-) < NO(3)(-) < SCN(-)). The roles
      of organic counterions are discussed on the basis of probable solubilization
      sites of the substrate molecule in the gemini micelles, showing more growth in
      case of Sal(-) than Benz(-). The results are confirmed in terms of the obtained
      values of chemical shift (delta), line width at half height (lw), and relative
      viscosity (eta(r)). Also, the growth of micelles was most pronounced for the
      gemini surfactant with the shortest spacer (s=4). This was attributed to the
      unique molecular structure of gemini surfactant micelles having flexible
      polymethylene spacer chain linking the twin polar headgroups.

PMID- 21194707
TI  - Solvothermal synthesis of InP quantum dots and their enhanced luminescent
      efficiency by post-synthetic treatments.
AB  - InP quantum dots (QDs) were solvothermally synthesized by using a greener
      phosphorus source of P(N(CH(3))(2))(3) instead of highly toxic P(TMS)(3) widely
      used, and subsequently subjected to a size-sorting processing. While as-grown QDs
      showed an undetectably low emission intensity, post-synthetic treatments such as
      photo-etching, photo-radiation, and photo-assisted ZnS shell coating gave rise to
      a substantial increase in emission efficiency due to the effective removal and
      passivation of surface states. The emission efficiency of the photo-etched QDs
      was further enhanced by a consecutive UV photo-radiation, attributable to the
      photo-oxidation at QD surface. Furthermore, a relatively thick ZnS shell on the
      surface of InP QDs that were surface-modified with hydrophilic ligands beforehand
      was photochemically generated in an aqueous solution at room temperature. The
      resulting InP/ZnS core/shell QDs, emitting from blue to red wavelengths, were
      more efficient than the above photo-treated InP QDs, and their luminescent
      properties (emission bandwidth and quantum yield) were comparable to those of InP
      QDs synthesized with P(TMS)(3). Structural, size, and compositional analyses on
      InP/ZnS QDs were also conducted to elucidate their core/shell structure.

PMID- 21194708
TI  - Photocatalytic degradation of phenolic syntan using TiO2 impregnated activated
      carbon.
AB  - Investigations were carried out to study the photocatalytic degradation of
      phenolic syntan (PS), a widely used environmentally polluting chemical in the
      leather tanning industry. Photocatalytic inactive commercial TiO(2) was used as
      the precursor for the preparation of TiO(2) impregnated activated carbon (Ti-AC)
      photocatalyst. Experiments were conducted by varying the concentrations of PS
      solution (50-1000 mg/l), pH (2.5-10) and time intervals to optimize the working
      parameters. A 254 nm UV light was used throughout the study. The effect of PS
      degradation using Ti-AC was also compared with direct UV photolysis. The Ti-AC
      was characterized using X-ray Diffraction (XRD), Diffuse Reflectance Spectroscopy
      (DRS), Scanning Electron Microscopy (SEM) and energy dispersive X-ray analysis
      (EDX) to determine the structural, optical, surface morphology and elemental
      analysis respectively. X-ray studies revealed the formation of catalytically
      active anatase phase in Ti-AC. Photodegradation of PS was examined by chemical
      oxygen demand (COD) method. PS degradation occurred at both the extreme end of
      acidic and alkaline pH conditions. However, the percentage degradation was
      comparatively higher at pH 2.5. The photodegradation followed pseudo first order
      kinetics. UV-Visible studies substantiated the occurrence of bathochromic and
      hyperchromic effects as a result of ring opening in the PS molecule.

PMID- 21194709
TI  - Dynamics of amphiphilic diblock copolymers at the air-water interface.
AB  - Two polyisoprene-polyethyleneoxide diblock copolymers with different block length
      ratios adsorbed to the water surface were investigated by multiple angle of
      incidence ellipsometry, evanescent wave light scattering, and surface tension
      experiments. In a semidilute interfacial regime, the transition from a two
      dimensional to a "mushroom" regime, in which polymer chains form loops and tails
      in the subphase, was discussed. A diffusion mechanism parallel to the interface
      was probed by evanescent wave dynamic light scattering. At intermediate
      concentrations, the interfacial diffusion coefficient D(?) scales with the
      surface concentration Gamma, as D(?) ~ Gamma(0.77) in agreement with the scaling
      observed for polymer solutions in a semidilute regime. At relatively high
      concentrations a decreasing of D(?) is discussed in terms of increasing friction
      due to interactions between polyisoprene chains.

PMID- 21194710
TI  - Effects of surfactant micelles on solubilization and DPPH radical scavenging
      activity of Rutin.
AB  - The interaction of the antioxidant Rutin with the radical DPPH (2,2-diphenyl-1
      picrylhydrazyl) in presence of cationic (CTAB, TTAB, DTAB), non-ionic (Brij78,
      Brij58, Brij35), anionic (SDS) and mixed surfactant systems (CTAB-Brij58, DTAB
      Brij35, SDS-Brij35) has been followed by spectrophotometric and tensiometric
      methods to evaluate the DPPH radical scavenging activity (RSA) of Rutin in these
      model self-assembled structures. The results show that the solubilization
      capacity of various single surfactant systems for both DPPH as well as Rutin
      followed the order cationics > non-ionics > anionic. The radical scavenging
      activity of Rutin in the solubilized form was higher within ionic micelles than
      in non-ionic micelles. However, the antioxidant exhibited enhanced activity for
      the radical in mixed cationic-non-ionic micelles compared with any of the single
      component micelles. In contrast, anionic-non-ionic mixed micelles modulated the
      activity of Rutin in-between that seen for pure anionic and non-ionic micelles
      only.

PMID- 21194712
TI  - The role of thiamine deficiency in konzo.

PMID- 21194711
TI  - The interrelationships of mathematical precursors in kindergarten.
AB  - This study evaluated the interrelations among cognitive precursors across
      quantitative, linguistic, and spatial attention domains that have been implicated
      for math achievement in young children. The dimensionality of the quantity
      precursors was evaluated in 286 kindergarteners via latent variable techniques,
      and the contribution of precursors from each domain was established for small
      sums addition. Results showed a five-factor structure for the quantity
      precursors, with the major distinction being between nonsymbolic and symbolic
      tasks. The overall model demonstrated good fit and strong predictive power
      (R(2)=55%) for addition number combinations. Linguistic and spatial attention
      domains showed indirect relationships with outcomes, with their effects mediated
      by symbolic quantity measures. These results have implications for the
      measurement of mathematical precursors and yield promise for predicting future
      math performance.

PMID- 21194713
TI  - No right to roam England's coast, yet.

PMID- 21194715
TI  - At last, a trawling ban for Hong Kong's inshore waters.

PMID- 21194714
TI  - Structure of microbial communities and hydrocarbon-dependent sulfate reduction in
      the anoxic layer of a polluted microbial mat.
AB  - The bacterial communities in the anoxic layer of a heavily polluted microbial mat
      and their growth on hydrocarbons under sulfate-reducing conditions were
      investigated. Microbial communities were dominated by members of
      Alphaproteobacteria (27% of the total rRNA), Planctomycetes (21.1%) and sulfate
      reducing bacteria (SRB: 17.5%). 16S rRNA cloning revealed sequences beloning to
      the same bacterial groups with SRB affiliated to the genera Desulfobulbus,
      Desulfocapsa, Desulfomicrobium, Desulfobacterium and
      Desulfosarcina/Desulfococcus. The derived enrichment cultures on crude oil,
      hexadecane and toluene were dominated by SRB. While most SRB sequences of the
      toluene and hexadecane cultures were related to the sequence of Desulfotignum
      toluolica, the crude oil enrichment showed a more diverse bacterial community
      with sequences from the genera Desulfotignum, Desulfobacter, Desulfatibacillus,
      Desulfosalina, and Desulfococcus. We conclude that the anoxic layer of the
      studied mats contains a diverse community of anaerobic bacteria, dominated by
      SRB, some of which are able to grow on hydrocarbons.

PMID- 21194716
TI  - Environmental toxicology: population modeling of cod larvae shows high
      sensitivity to loss of zooplankton prey.
AB  - Two factors determine whether pollution is likely to affect a population
      indirectly through loss of prey: firstly, the sensitivity of the prey to the
      pollutants, and secondly, the sensitivity of the predator population to loss of
      prey at the given life stage. We here apply a statistical recruitment model for
      Northeast Arctic cod to evaluate the sensitivity of cod cohorts to loss of
      zooplankton prey, for example following an oil spill. The calculations show that
      cod cohorts are highly sensitive to possible zooplankton biomass reductions in
      the distribution area of the cod larvae, and point to a need for more knowledge
      about oil-effects on zooplankton. Our study illustrates how knowledge about
      population dynamics may guide which indirect effects to consider in environmental
      impact studies.

PMID- 21194717
TI  - Effect of different environmental stresses on the expression of oleate desaturase
      genes and fatty acid composition in olive fruit.
AB  - The regulation of microsomal and plastidial oleate desaturases by low and high
      temperature, darkness, and wounding was investigated. To this end, their gene
      expression levels and the fatty acid composition was determined in the mesocarp
      tissue of olive fruit from the Picual and Arbequina varieties subjected to the
      corresponding stress treatments. Firstly, a plastidial oleate desaturase from
      olive was cloned and its functional identity was confirmed by overexpression in
      Escherichia coli. The results showed that temperature and light regulate olive
      oleate desaturase genes at transcriptional level. However, no correlation between
      their expression levels and the linoleic acid content in microsomal and
      plastidial lipids was found. In addition, the involvement of microsomal but not
      plastidial oleate desaturases in the wounding response of olive fruit mesocarp is
      demonstrated. The fatty acid analysis revealed the appearance of palmitolinoleic
      acid only in microsomal lipids, reaching a maximum 3h after wounding.

PMID- 21194718
TI  - Angioarchitecture of the bovine tunica albuginea vascular complex--a corrosive
      and histological study.
AB  - Histological and corrosive studies of 75 bovine testes were focused on the
      vascular complex of the tunica albuginea. Thanks to used MultiScanBase v.14.02
      software arterial and venous vessels and also vascular anastomoses were analyzed
      preciously. The studies revealed the superficial layer containing vessels of
      smaller diameter and reduced wall structure and the deeper layer with wider,
      winding vessels and complete wall structure. The branches of the testicular
      artery and intra-tunical veins formed a vascular complex of the tunica albuginea.
      The intra-tunical veins were divided into two types. Type I veins ran parallel,
      drained intra-parenchymal veins and formed the origin of pampiniform plexus. Type
      II veins drained into type I intra-tunical veins. Indirect anastomoses among
      intra-tunical veins and arteries and venovenous connections were observed. The
      results of the study could contribute fuller description of the regulatory
      mechanism for testicular blood supply and optimization of the testicular biopsy
      to minimize bleeding risk.

PMID- 21194719
TI  - Liver haemodynamics as they relate to portosystemic shunts in the dog: a review.
AB  - There are several factors at play in the homeostatic regulation of hepatic blood
      flow. These include neovascularisation and other intrahepatic shunting of blood
      away from sinusoids and obstructed hepatic veins. Current surgical techniques
      used in the management of portosystemic shunts in the dog modify the flow of
      portal blood to the liver or of hepatic venous blood from the liver. Such
      modifications may have significant consequences in terms of long term liver
      perfusion. This review considers the haemodynamics within the normally perfused
      liver as well as those within the liver who's blood supply has been modified.

PMID- 21194720
TI  - [Botulinum toxin and painful peripheral neuropathies: what should be expected?].
AB  - Botulinum toxin type A (BTX-A) is a potent neurotoxin that blocks acetylcholine
      release from presynaptic nerve terminals by cleaving the SNARE complex. BTX-A has
      been reported to have analgesic effects independent of its action on muscle tone.
      The most robust results have been observed in patients with neuropathic pain.
      Neuropathic pain due to peripheral lesions has been the most widely studied. BTX
      A has shown its efficacy on pain and allodynia in various animal models of
      inflammatory neuropathic pain. The only randomized, double-blind, placebo
      controlled trial in patients with focal painful neuropathies due to nerve trauma
      or postherpetic neuralgia demonstrated significant effects on average pain
      intensity from 2 weeks after the injections to 14 weeks. Most patients reported
      pain during the injections, but there were no further local or systemic side
      effects. The efficacy of BTX-A in painful peripheral neuropathies has been more
      recently studied. Results were positive in the only study in an animal model of
      peripheral neuropathy. One study in patients with diabetic painful peripheral
      neuropathy demonstrated a significant decrease in Visual Analog Scale. In
      conclusion, one session of multiple intradermal injection of BTX-A produces long
      lasting analgesic effects in patients with focal painful neuropathies and
      diabetic neuropathic pain, and is particularly well tolerated. The findings are
      consistent with a reduction of peripheral sensitisation, the place of a possible
      central effect remaining to define. Further studies are needed to assess some
      important issues, i.e. BTX-A efficacy in patients with small fiber neuropathies
      and the relevance of early and repeated injections. Future studies could also
      provide valuable insights into pathophysiology of neuropathic pain.

PMID- 21194721
TI  - Comparison of MFI-UF constant pressure, MFI-UF constant flux and Crossflow
      Sampler-Modified Fouling Index Ultrafiltration (CFS-MFI UF).
AB  - Understanding the foulant deposition mechanism during crossflow filtration is
      critical in developing indices to predict fouling propensity of feed water for
      reverse osmosis (RO). Factors affecting the performance on different fouling
      indices such as MFI-UF constant pressure, MFI-UF constant flux and newly proposed
      fouling index, CFS-MFI(UF) were investigated. Crossflow Sampler-Modified Fouling
      Index Ultrafiltration (CFS-MFI(UF)) utilises a typical crossflow unit to simulate
      the hydrodynamic conditions in the actual RO units followed by a dead-end unit to
      measure the fouling propensity of foulants. CFS-MFI(UF) was found sensitive to
      crossflow velocity. The crossflow velocity in the crossflow sampler unit
      influences the particle concentration and the particle size distribution in its
      permeate. CFS-MFI(UF) was also found sensitive to the permeate flux of both CFS
      and the dead-end cell. To closely simulate the hydrodynamic conditions of a
      crossflow RO unit, the flux used for CFS-MFI(UF) measurement was critical. The
      best option is to operate both the CFS and dead-end permeate flux at flux which
      is normally operated at industry RO units (~20 L/m(2)h), but this would prolong
      the test duration excessively. In this study, the dead-end flux was accelerated
      by reducing the dead-end membrane area while maintaining the CFS permeate flux at
      20 L/m(2)h. By doing so, a flux correction factor was investigated and applied to
      correlate the CFS-MFI(UF) measured at dead-end flux of 120 L/m(2)h to CFS-MFI(UF)
      measured at dead-end flux of 20 L/m(2)h for RO fouling rate prediction. Using
      this flux correction factor, the test duration of CFS-MFI(UF) can be shortened
      from 15 h to 2h.

PMID- 21194722
TI  - Effects of malathion and chlorpyrifos on acetylcholinesterase and antioxidant
      defense system in Oxya chinensis (Thunberg) (Orthoptera: Acrididae).
AB  - The study was undertaken to evaluate the effects of malathion and chlorpyrifos on
      acetylcholinesterase (AChE), esterase (EST) activity and antioxidant system after
      topical application with different concentration to Oxya chinensis. The results
      showed that malathion and chlorpyrifos inhibited EST, AChE activity and increased
      malondialdehyde (MDA) contents. A change in superoxide dismutase (SOD), catalase
      (CAT), glutathione S-transferase (GST), glutathione peroxidase (GPx), and
      glutathione reductase (GR) activity combined with reduced glutathione (GSH) and
      total glutathione (tGSH) contents was found in O. chinensis after malathion and
      chlorpyrifos treatments. Malathion and chlorpyrifos increased SOD and CAT
      activity compared with the control. With the concentrations increasing, SOD and
      CAT activity showed the similar tendency, namely, SOD and CAT activity increased
      at the lower concentrations and decreased at the higher concentrations. The
      results showed that malathion and chlorpyrifos decreased significantly GR
      activity. GST and GPx activity at the studied concentrations of chlorpyrifos was
      lower than that of the control. However, no significance was observed. GPx and
      GST activity in malathion treated grasshoppers showed a biphasic response with an
      initial increase followed by a decline in its activity. Malathion and
      chlorpyrifos decreased GSH contents and the ratio of GSH/GSSG. The present
      findings indicated that the toxicity of malathion and chlorpyrifos might be
      associated with oxidative stress.

PMID- 21194723
TI  - Biotransformation of 17alpha-methyltestosterone in sediment under different
      electron acceptor conditions.
AB  - 17alpha-Methyltestosterone (MT), an anabolic androgenic steroid, is used widely
      in inducing an all male population in aquaculture farming of fish, such as Nile
      tilapia (Oreochromis niloticus). Current understanding of the occurrence and fate
      of MT in the sediments and the surrounding areas of the aquaculture ponds are
      very limited. Bioassay tests showed that MT was biotransformed under aerobic and
      sulfate-reducing conditions with a half-life of 3.8d and 5.3d, respectively, with
      complete disappearance of androgenic activity. However, under methanogenic
      condition, MT was found to biotransform but the androgenic activity continued to
      persist even after 45 d of incubation. In contrast, MT was found to transform
      slowly under iron(III)-reducing condition and was hardly transformed under
      nitrate-reducing condition. A possible reason for the lack of transformation of
      MT under nitrate-reducing condition is the presence of the methyl group at the C
      17 position. The results of this study suggest that MT and its degradation
      products with androgenic activity may potentially accumulate in the sediments of
      fish farming ponds under iron(III)-reducing, nitrate-reducing and methanogenic
      conditions.

PMID- 21194724
TI  - Integrated biological responses of zebrafish (Danio rerio) to analyze water
      quality in regions under anthropogenic influence.
AB  - This study analyzed water quality in regions around Patos lagoon (Southern
      Brazil) that are under anthropogenic pressure. Water samples were collected from
      five different sites, including one used as a source for human consumption (COR)
      and others known to be influenced by human activities (IP). Danio rerio
      (Teleostei, Cyprinidae) organisms were exposed for 24h to these water samples,
      plus a control group. It was observed that: (1) reactive oxygen species levels
      were lower in COR and IP than in the control group; (2) glutamate-cysteine ligase
      (catalytic subunit) expression was higher in COR than in other sites; (3)
      exposure to all water samples affected long-term memory (LTM) when compared to
      control group. Thus, some water samples possess the ability to modulate the
      antioxidant system and to induce a decline in cognitive functions, as measured by
      LTM. The obtained results indicate that a combination of variables of different
      organization level (molecular, biochemical and behavioral) can be employed to
      analyze water quality in impacted regions.

PMID- 21194725
TI  - Quantitative determination of fluorochemicals in municipal landfill leachates.
AB  - Twenty-four fluorochemicals were quantified in landfill leachates recovered from
      municipal refuse using an analytical method based on solid-phase extraction,
      dispersive-carbon sorbent cleanup, and liquid chromatography/tandem mass
      spectrometry. The method was applied to six landfill leachates from four
      locations in the US as well as to a leachate generated by a laboratory bioreactor
      containing residential refuse. All seven leachates had the common characteristic
      that short-chain (C(4)-C(7)) carboxylates or sulfonates were greater in abundance
      than their respective longer-chain homologs (>= C(8)). Perfluoroalkyl
      carboxylates were the most abundant (67 +/- 4% on a nanomolar (nM) basis)
      fluorochemicals measured in leachates; concentrations of individual carboxylates
      reaching levels up to 2800 ng L(-1). Perfluoroalkyl sulfonates were the next most
      abundant class (22 +/- 2%) on a nM basis; their abundances in each of the seven
      leachates derived from municipal refuse were greater for the shorter-chain
      homologs (C(4) and C(6)) compared to longer-chain homologs (C(8) and C(10)).
      Perfluorobutane sulfonate concentrations were as high as 2300 ng L(-1).
      Sulfonamide derivatives composed 8 +/- 2.1% (nM basis) of the fluorochemicals in
      landfill leachates with methyl (C(4) and C(8)) and ethyl (C(8)) sulfonamide
      acetic acids being the most abundant. Fluorotelomer sulfonates (6:2 and 8:2)
      composed 2.4 +/- 1.3% (nM basis) of the fluorochemicals detected and were present
      in all leachates.

PMID- 21194726
TI  - Photocatalytic degradation of the fungicide Fenhexamid in aqueous TiO(2)
      suspensions: identification of intermediates products and reaction pathways.
AB  - Liquid-chromatography interfaced with time-of-flight mass spectrometry (LC
      TOF/MS) was used to separate and characterize the transformation products arising
      from TiO(2)-photocatalytic degradation of the fungicide Fenhexamid (FEX) in
      aqueous solution under simulated solar irradiation. Prior to identification,
      irradiated solutions of FEX (10mgL(-1)) were concentrated by solid-phase
      extraction. Assignments of the mass spectra ions were aided by elemental
      composition calculations, comparison of structural analogues and available
      literature, and acquired knowledge regarding mass spectrometry of related
      heterocyclic compounds. The primary transformation intermediates identified were
      hydroxyl and/or keto-derivatives. Several positional isomers are typically
      produced as a consequence of the non-selectivity of the ()OH radical attack.
      Moreover, products resulted from the cleavage of the amide and NH-dichlorophenol
      bonds were formed. Finally, cyclic - benzo[d]oxazole intermediates are also
      formed through an intramolecular photocyclization process and cleavage of halogen
      - carbon bond. In the case of the hydroxy and/or keto-derivatives, the generic
      fragmentation scheme obtained from the interpretation of the ESI-TOF-MS data
      cannot be diagnostic to precisely localize the position of the entering
      substituent on the FEX molecule, and thus to characterize all its possible
      oxygenated derivatives by assigning a plausible structure with confidence. On the
      basis of identified products different pathways of photocatalytic degradation of
      FEX were proposed and discussed.

PMID- 21194727
TI  - The expression profile of RNA-binding proteins in primary and metastatic
      colorectal cancer: relationship of heterogeneous nuclear ribonucleoproteins with
      prognosis.
AB  - The heterogeneous nuclear ribonucleoproteins are a group of RNA-binding proteins
      with a range of key cellular functions, which are dysregulated in tumorigenesis
      including regulation of translational and RNA processing. The aims of this study
      were to define the heterogeneous nuclear ribonucleoprotein expression profile in
      primary and metastatic colorectal cancer and to establish the clinicopathologic
      significance of this expression. A tissue microarray containing 515 primary
      colorectal cancers, 224 lymph node metastasis of colorectal cancer, and 50 normal
      colon samples was immunostained for 6 heterogeneous nuclear ribonucleoproteins.
      Heterogeneous nuclear ribonucleoprotein I, heterogeneous nuclear
      ribonucleoprotein K, and heterogeneous nuclear ribonucleoprotein L displayed the
      most frequent strong immunoreactivity in primary colorectal tumor samples.
      Heterogeneous nuclear ribonucleoprotein A1 (P < .001) and heterogeneous nuclear
      ribonucleoprotein U (P = .003) showed significant alterations in nuclear
      expression in tumors compared with normal colonic epithelium, whereas
      heterogeneous nuclear ribonucleoprotein A1 (P = .001), heterogeneous nuclear
      ribonucleoprotein I (P < .001), and heterogeneous nuclear ribonucleoprotein K (P
      < .001) all showed significant aberrant cytoplasmic immunoreactivity in tumor
      cells. There were also significant differences in cytoplasmic immunoreactivity
      between the primary tumor and the corresponding lymph node metastasis for
      heterogeneous nuclear ribonucleoprotein A1 (P = .001), heterogeneous nuclear
      ribonucleoprotein I (P < .001), and heterogeneous nuclear ribonucleoprotein K (P
      = .001). Nuclear heterogeneous nuclear ribonucleoprotein H (chi(2) = 72.1; P <
      .001), cytoplasmic heterogeneous nuclear ribonucleoprotein I (chi(2) = 28.1; P <
      .001), and cytoplasmic heterogeneous nuclear ribonucleoprotein K (chi(2) = 13.2;
      P = .04) all showed significant associations with tumor stage. There was a
      significant relationship between strong nuclear heterogeneous nuclear
      ribonucleoprotein H expression and survival (chi(2) = 14.97; P < .001). This
      study has defined the expression profile of heterogeneous nuclear
      ribonucleoproteins in colorectal cancer and shown that there are significant
      alterations in both expression and subcellular localization of individual
      heterogeneous nuclear ribonucleoproteins in this type of tumor.

PMID- 21194728
TI  - Mucinous tubular and spindle cell carcinoma of kidney without sarcomatoid change
      showing metastases to liver and retroperitoneal lymph node.
AB  - Mucinous tubular and spindle cell carcinoma (MTSCC) is an uncommon, newly
      recognized tumor that in its classic histological form shows tightly packed,
      elongated tubules with transition into spindle cell areas and pale mucinous
      stroma. The current data suggest that the great majority of MTSCCs have a
      favorable prognosis; however, the follow-up data are limited and the full
      biologic potential of this tumor remains to be established. There are a few
      examples of MTSCCs metastatic to lymph nodes and rare cases with sarcomatoid
      differentiation associated with distant metastases. We report on a case of MTSCC
      of kidney with concurrent nodal and liver metastases. The metastatic nodules were
      well circumscribed and showed morphological and immunophenotypic features similar
      to those of the primary tumor. Extensive sampling revealed no evidence of
      sarcomatoid morphology. To our knowledge, this is the first case of MTSCC without
      sarcomatoid differentiation showing parenchymal metastasis.

PMID- 21194729
TI  - CD1a immunopositivity in perivascular epithelioid cell neoplasms: true expression
      or technical artifact? A streptavidin-biotin and polymer-based detection system
      immunohistochemical study of perivascular epithelioid cell neoplasms and their
      morphologic mimics.
AB  - Perivascular epithelioid cell neoplasms comprise a family of rare neoplasms
      composed of morphologically distinctive perivascular epithelioid cells exhibiting
      a "myomelanocytic" immunophenotype. The distinction of perivascular epithelioid
      cell neoplasms from other tumors with melanocytic and smooth muscle
      differentiation can be difficult. A recent study has suggested that perivascular
      epithelioid cell neoplasms routinely express CD1a, a Langerhans cell-associated
      transmembrane glycoprotein involved in antigen presentation and that expression
      of this marker may be helpful in the distinction of perivascular epithelioid cell
      neoplasms from various mimics. We evaluated a series of perivascular epithelioid
      cell neoplasms and potential mimics for CD1a expression. A total of 54 cases (27
      perivascular epithelioid cell neoplasms, 11 leiomyosarcomas, 10 melanomas, 6
      clear cell sarcomas) were evaluated in 2 laboratories (Mayo Clinic Rochester: 31
      cases, Carolinas Medical Center: 23 cases). Selected positive cases were retested
      at Carolinas Medical Center (11 cases) and Mayo Clinic Rochester (10 cases). Mayo
      Clinic Rochester methods were as follows: MTB1 clone (1:20, Novocastra, Newcastle
      upon-Tyne, UK), heat-induced epitope retrieval in EDTA (pH 8.0), and Dako Advance
      detection system (Dako Corp, Carpinteria, CA) with background-reducing diluent.
      Carolinas Medical Center methods were as follows: MTB1 clone (1:30; CellMarque,
      Rocklin, CA), heat-induced epitope retrieval in Medium Cell Conditioner #1 (pH
      8.0-9.0), and streptavidin-biotin detection system with diaminobenzidine
      chromogen, with and without biotin blocking. Scores were as follows: 1+, 5% to
      25%; 2+, 26% to 50%; and 3+, more than 51%. Langerhans cells served as a positive
      internal control in all tested cases. All Mayo Clinic Rochester cases were
      negative. Sixteen Carolinas Medical Center perivascular epithelioid cell
      neoplasms (14 renal angiomyolipomas, 1 soft tissue perivascular epithelioid cell
      neoplasm, 1 pulmonary clear cell "sugar" tumor) showed CD1a immunopositivity (1+:
      7 cases; 2+: 7 cases; 3+: 2 cases) when tested without biotin blocking, 11 of
      these cases were retested with biotin blocking and were negative. All non
      perivascular epithelioid cell neoplasms were negative. All positive perivascular
      epithelioid cell neoplasms showed cytoplasmic staining only, without membranous
      staining. Ten Carolinas Medical Center positive perivascular epithelioid cell
      neoplasms were negative when retested a Mayo Clinic Rochester, using a polymer
      based detection system. We conclude that perivascular epithelioid cell neoplasms
      do not truly express CD1a in a biologically plausible membranous pattern, but may
      instead show aberrant cytoplasmic immunopositivity in some laboratories. Close
      inspection of published photomicrographs of previously reported CD1a-positive
      perivascular epithelioid cell neoplasms shows an identical pattern of cytoplasmic
      positivity, likely reflecting abundant endogenous biotin within perivascular
      epithelioid cell neoplasm cells. We do not believe that there is a role for CD1a
      immunohistochemistry in the differential diagnosis of perivascular epithelioid
      cell neoplasms.

PMID- 21194730
TI  - Estimation of the contribution of ultrafine particles to lung deposition of
      particle-bound mutagens in the atmosphere.
AB  - The present study was performed to estimate the contributions of fine and
      ultrafine particles to the lung deposition of particle-bound mutagens in the
      atmosphere. This is the first estimation of the respiratory deposition of
      atmospheric particle-bound mutagens. Direct and S9-mediated mutagenicity of size
      fractionated particulate matter (PM) collected at roadside and suburban sites was
      determined by the Ames test using Salmonella typhimurium strain TA98. Regional
      deposition efficiencies in the human respiratory tract of direct and S9-mediated
      mutagens in each size fraction were calculated using the LUDEP computer-based
      model. The model calculations showed that about 95% of the lung deposition of
      inhaled mutagens is caused by fine particles for both roadside and suburban
      atmospheres. Importantly, ultrafine particles were shown to contribute to the
      deposition of mutagens in the alveolar region of the lung by as much as 29% (+S9)
      and 26% (-S9) for the roadside atmosphere and 11% (+S9) and 13% (-S9) for the
      suburban atmosphere, although ultrafine particles contribute very little to the
      PM mass concentration. These results indicated that ultrafine particles play an
      important role as carriers of mutagens into the lung.

PMID- 21194731
TI  - Assessment of skin exposure to N,N-dimethylformamide and methyl ethylketone
      through chemical protective gloves and decontamination of gloves for reuse
      purposes.
AB  - N,N-dimethylformamide (DMF) and methyl ethylketone (MEK) are the hazardous
      chemicals commonly used in the synthetic leather industries. Although chemical
      protective gloves provide adequate skin exposure protection to workers in these
      industries, there is currently no clear guideline or understanding with regard to
      the use duration of these gloves. In this study, the permeation of DMF/MEK
      mixture through neoprene gloves and the desorption of chemicals from contaminated
      gloves were conducted using the ASTM F739 cell. The acceptable use duration time
      of the gloves against DMF/MEK permeation was estimated by assuming a critical
      body burden of chemical exposure as a result of dermal absorption. In a re
      exposure cycle of 5 days, decontamination of the gloves by aeration at 25 degrees
      C was found to be inadequate in a reduction of breakthrough time as compared to a
      new unexposed glove. However, decontamination of the gloves by heating at 70 or
      100 degrees C showed that the protective coefficient of the exposed gloves had
      similar levels of resistance to DMF/MEK as that of new gloves. Implications of
      this study include an understanding of the use duration of neoprene gloves and
      proper decontamination of chemical protective gloves for reuse.

PMID- 21194732
TI  - Electron microscopic immunogold localization of salivary mucin MUC5B in human
      buccal and palatal glands.
AB  - In recent years, minor salivary glands, due to their involvement in the health
      and homeostasis of the oral cavity, have been the focus of several research
      investigations. Despite the fact that a considerable amount of data has been
      collected, many aspects of their functional features, including the secretory
      components they produce, remain to be ascertained. In this study we have analyzed
      the ultrastructural distribution of the MUC5B mucin in human palatal and buccal
      glands by means of post-embedding immunoelectron microscopy. Thin sections of
      normal human buccal and palatal glands obtained at surgery, were treated with
      polyclonal antibodies to human salivary MUC5B. Intense MUC5B reactivity was
      observed in the secretory granules of mucous cells of all glands examined. The
      present results provide new data regarding the secretory pattern of MUC5B in
      human buccal and palatal glands, indicating their significant contribution to the
      maintenance of the mucous biofilm that protects buccal and palatal mucosal areas.

PMID- 21194733
TI  - Stereotactic body radiotherapy (SBRT): Technological innovation and application
      in gynecologic oncology.
AB  - OBJECTIVES: Stereotactic body radiotherapy (SBRT) is a novel form of noninvasive,
      highly conformal radiation treatment that delivers a high dose to tumor. The
      advantage of the technique resides in its ability to provide a high dose to tumor
      but spare normal tissues to an extent not previously possible. In this paper we
      will provide an introduction and review of this technology with regard to its use
      in gynecologic malignancies. Preliminary results from our experience are
      presented for the purpose of illustrating the range of SBRT applications in
      gynecologic oncology. METHODS: A comprehensive literature review was conducted
      and our experience from the past three years was reviewed. RESULTS: Six case
      series are published that report results of SBRT for gynecologic malignancies.
      Sixteen gynecologic patients have been treated with SBRT at our institution.
      Treatment sites include pelvic and periaortic nodes (9 patients), oligometastatic
      disease (2), and cervical or endometrial primary tumors when other conventional
      external radiation or brachytherapy techniques were unsuitable (5). Preliminary
      follow-up at a median of 11 months (range, 0.3-33 months) demonstrates 79%
      locoregional control, 43% distant failure, and 50% overall survival. CONCLUSIONS:
      SBRT boosts to macroscopic periaortic node recurrences and other sites seem to
      provide local control and a possibility of long-term disease-free survival in
      carefully selected patients. Previously this had been difficult to achieve with
      conventional radiotherapy because of the proximity of periaortic nodes to small
      bowel. SBRT also offers a novel approach for minimally invasive treatment in the
      management of gynecological cancer where current surgical and radiotherapy
      techniques are unsuitable.

PMID- 21194734
TI  - High-risk human papillomavirus DNA test and p16(INK4a) in the triage of LSIL: a
      prospective diagnostic study.
AB  - OBJECTIVE: The detection of high-grade cervical intraepithelial neoplasia (CIN)
      amongst patients with low-grade cytology (LSIL) is challenging. This study
      evaluated the role of high-risk HPV (HR-HPV) DNA test and p16(INK4a)
      immunostaining in identifying women with LSIL cytology at risk of harboring CIN2
      or worse (CIN2+) and the role of p16(INK4a) in the triage of a population of HR
      HPV positive LSIL. METHODS: We conducted a prospective study including women with
      LSIL cytology. Detection of HR-HPV was carried out by means of a polymerase chain
      reaction based assay. p16(INK4a) immunostaining was performed using the Dako
      CINtec cytology kit. All patients had colposcopically directed punch biopsies or
      large loop excision of the transformation zone of the cervix. The endpoint was
      detection of a biopsy-confirmed CIN2+. RESULTS: A series of 126 women with LSIL
      cytology were included. HR-HPV test had sensitivity 75% and specificity 64% for
      an endpoint of CIN2+. p16(INK4a) had significantly higher specificity of 89%
      (p=0.0000) but low sensitivity of 42%. The role of p16(INK4a) immunostaining in
      the triage of LSIL positive for HR-HPV was also evaluated. p16(INK4a) triage had
      70% positive predictive value (PPV); however, this was not significantly higher
      than the PPV (56%) of HR-HPV test alone (p=0.4). CONCLUSIONS: The results
      indicate that HR-HPV or p16(INK4a) cannot be used as solitary markers for the
      assessment of LSIL. The addition of p16(INK4a) immunostaining led to an increase
      in HR-HPV specificity; however, the biomarker needs to be assessed further to
      establish its role as an adjunct test in the triage of LSIL.

PMID- 21194735
TI  - A comparative detail analysis of the learning curve and surgical outcome for
      robotic hysterectomy with lymphadenectomy versus laparoscopic hysterectomy with
      lymphadenectomy in treatment of endometrial cancer: a case-matched controlled
      study of the first one hundred twenty two patients.
AB  - GOAL: To determine the learning curve and surgical outcome for the first one
      hundred twenty-two robotic hysterectomy with lymphadenectomy patients in
      comparison to the first one hundred twenty-two patients who underwent the same
      procedure laparoscopically. MATERIALS AND METHODS: An analysis of the first 122
      patients who underwent a robotic assisted hysterectomy with lymphadenectomy
      (RHBPPALND) was compared to the first 122 patients who underwent a total
      laparoscopic hysterectomy with lymphadenectomy (LHBPPALND). The learning curve of
      the surgical procedure was determined by measuring operative time with respect to
      chronological order of each patient who had undergone their respective procedure.
      Number of lymph nodes, estimated blood loss, days of hospitalization, and
      complications of all patients were also analyzed and compared. RESULTS: The
      learning curve of the surgical procedure was determined by measuring operative
      time with respect to chronological order of each patient who had undergone their
      respective procedure. Data were analyzed for mean age, body mass index, operative
      time, estimated blood loss, lymph node retrieval and complications for both
      surgical procedures. The mean operative time was 147.2+/-48.2 and 186.8+/-59.8
      for RHBPPALND and LHBPPALND respectively. The mean EBL was statistically
      significant at 81.1+/-45.9 and 207.4+/-109.4 for RHBPPALND and LHBPPALND
      respectively. The total number of pelvic and aortic lymph nodes was 25.1+/-12.7
      for RHBPPALND and 43.1+/-17.8 for LHBPPALND. The number of pelvic lymph node was
      19.2+/-9.0 and 24.7+/-11.9 for RHBPPALND and LHBPPALND. The days of
      hospitalization of RHBPPALND and LHBPPALND were 1.5+/-0.9 and 3.2+/-2.3. The
      number of intraoperative complications for RHBPPALND, and LHBPPALND was 1 and 7,
      respectively. CONCLUSION: Robotic hysterectomy with lymphadenectomy has a faster
      learning curve in comparison to laparoscopic hysterectomy with lymphadenectomy.
      The adequacy of surgical staging was comparable between the two surgical methods.
      RHBPPALND is associated with shorter hospitalization, less blood loss and less
      intraoperative and major complications, and lower rate of conversion to open
      procedure.

PMID- 21194736
TI  - Robotic approach for ovarian cancer: perioperative and survival results and
      comparison with laparoscopy and laparotomy.
AB  - OBJECTIVE: Comparison of perioperative outcomes and survival of patients
      undergoing primary surgical treatment for epithelial ovarian cancer (EOC) by a
      robotic, laparoscopy, or laparotomy approach. METHODS: Retrospective case-control
      analysis of 25 patients with EOC undergoing robotic surgical treatment between
      March 2004 and December 2008. Comparison was made with similar patients treated
      by laparoscopy and laparotomy and matched by age, body mass index (BMI), and type
      of procedures between January 1999 and December 2006. RESULTS: The mean operating
      times were 314.8, 253.8 and 260.7 min for robotic, laparoscopy and laparotomy
      patients, respectively (p<0.05); the mean blood loss was 164.0, 266.7, and 1307.0
      ml, respectively (p=0.001); the mean length of hospital stay was 4.2, 3.2, and
      9.4 days, respectively (p=0.001). The overall survival (OS) for robotics,
      laparoscopy and laparotomy patients was 67.1%, 75.6% and 66.0%, respectively
      (p=0.08). Patients were subdivided and compared according to the extent of
      surgery by the type and number of major procedures. Type I and II debulking
      patients operated by robotics and laparoscopy had improved perioperative outcomes
      as compared to laparotomy. For patients undergoing a type III debulking, robotic
      outcomes were not improved over laparotomy. CONCLUSION: Laparoscopy and robotics
      are preferable to laparotomy for patients with ovarian cancer requiring primary
      tumor excision alone or with one additional major procedure. Laparotomy is
      preferable for patients requiring two or more additional major procedures.
      Survival is not affected by the type of surgical approach.

PMID- 21194737
TI  - The incidence of isolated para-aortic nodal metastasis in completely staged
      endometrial cancer patients.
AB  - OBJECTIVE: To describe and review the incidence of para-aortic (PA) nodal
      metastasis in completely staged endometrial cancer patients who are negative for
      pelvic nodal metastasis. METHODS: Using an institutionally maintained database,
      we identified all patients with endometrial cancer from 2002 to 2006 who had both
      pelvic and aortic nodal dissections and determined the rate of isolated para
      aortic nodal metastasis in non-malignant (i.e. negative) pelvic nodes. RESULTS:
      201 endometrial cancer patients were surgically treated at our institution from
      2002 to 2006. 171 patients had both pelvic and PA nodes removed during surgery,
      and specimens examined by a pathologist. Only 2 (1.2%) had PA nodes that tested
      positive for malignance (i.e. positive PA nodes) with pelvic nodes that tested
      negative for malignance (i.e. negative pelvic nodes). The final International
      Federation of Gynecology and Obstetrics (FIGO) grade for the endometrial tumor
      cells in the two patients was "G1" with endometrioid adenocarcinoma and "G3" with
      endometrioid adenocarcinoma and mucinous differentiation, respectively.
      CONCLUSION: Based on the very low incidence of patients inflicted with
      endometrial cancer that have positive para-aortic lymph nodes (PALNs) with
      negative pelvic nodes found both in our literature review (1.5%) and in our own
      study (1.2%), the addition of PA lymphadenectomy in all patients was found to
      have minimal diagnostic and therapeutic value. At the present, the role of
      complete PA lymphadenectomy in all patients with endometrial cancer should be re
      examined. Individualized algorithms should be developed based on risk factors and
      status of pelvic nodes.

PMID- 21194738
TI  - A validation study of the new revised FIGO staging system to estimate prognosis
      for patients with stage IIIC endometrial cancer.
AB  - OBJECTIVE: The aim of this study was to validate the role of the new FIGO staging
      system for estimating prognosis for patients with stage IIIC endometrial cancer.
      METHODS: A total of 93 cases with stage IIIC were entered in this study and
      classified into three groups: one group of patients who underwent pelvic
      lymphadenectomy (PLX) and para-aortic lymphadenectomy (PALX) and who were for
      positive for pelvic node metastasis (PLNM) and negative for para-aortic node
      metastasis (PANM) (Group 1), one group of patients who underwent PLX alone and
      were positive for PLNM (Group 2) and one group of patients who underwent PLX and
      PALX and were positive for PANM (Group 3). Information on clinicopathologic
      findings and treatments was obtained from medical charts. Cox regression analysis
      was used to select prognostic factors. RESULTS: The 5-years survival rates were
      89.3% in Group 1, 46.5% in Group 2 and 59.9% in Group 3. The overall survival
      rate in Group 1 was significantly better than that in Group 2 (p=0.0001) and
      Group 3 (p=0.0016). No significant difference in overall survival was found
      between Group 2 and Group 3. Age, number of metastatic lymph nodes, type of
      lymphadenectomy and type of adjuvant therapy were significantly and independently
      related to overall survival. Only when patients received PALX, PANM was a
      prognostic risk factor. CONCLUSION: Sub-classification of stage IIIC would be
      functional for estimating prognosis in the revised FIGO staging system.
      Systematic lymphadenectomy including PALX has therapeutic significance for
      patients with stage IIIC endometrial cancer. Prognosis of patients with stage
      IIIC endometrial cancer would depend much more on application of lymphadenectomy
      including PALX than nodal status.

PMID- 21194739
TI  - BRCA1 methylation and BRCA1 mutations in ovarian cancer.

PMID- 21194741
TI  - Surveillance of the cost of asthma in the 21st century.

PMID- 21194740
TI  - Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally
      controlled asthma.
AB  - BACKGROUND: Improvement in lung function after macrolide antibiotic therapy has
      been attributed to reduction in bronchial infection by specific bacteria.
      However, the airway might be populated by a more diverse microbiota, and clinical
      features of asthma might be associated with characteristics of the airway
      microbiota present. OBJECTIVE: We sought to determine whether relationships exist
      between the composition of the airway bacterial microbiota and clinical features
      of asthma using culture-independent tools capable of detecting the presence and
      relative abundance of most known bacteria. METHODS: In this pilot study bronchial
      epithelial brushings were collected from 65 adults with suboptimally controlled
      asthma participating in a multicenter study of the effects of clarithromycin on
      asthma control and 10 healthy control subjects. A combination of high-density 16S
      ribosomal RNA microarray and parallel clone library-sequencing analysis was used
      to profile the microbiota and examine relationships with clinical measurements.
      RESULTS: Compared with control subjects, 16S ribosomal RNA amplicon
      concentrations (a proxy for bacterial burden) and bacterial diversity were
      significantly higher among asthmatic patients. In multivariate analyses airway
      microbiota composition and diversity were significantly correlated with bronchial
      hyperresponsiveness. Specifically, the relative abundance of particular
      phylotypes, including members of the Comamonadaceae, Sphingomonadaceae,
      Oxalobacteraceae, and other bacterial families were highly correlated with the
      degree of bronchial hyperresponsiveness. CONCLUSION: The composition of bronchial
      airway microbiota is associated with the degree of bronchial hyperresponsiveness
      among patients with suboptimally controlled asthma. These findings support the
      need for further functional studies to examine the potential contribution of
      members of the airway microbiota in asthma pathogenesis.

PMID- 21194742
TI  - Parental psychosocial stress and asthma morbidity in Puerto Rican twins.
AB  - BACKGROUND: Little is known about paternal psychosocial factors and childhood
      asthma. OBJECTIVE: We sought to examine the link between maternal and paternal
      psychosocial stress and asthma outcomes in young children. METHODS: Parents of
      339 pairs of Puerto Rican twins were interviewed individually about their own
      psychosocial stress and about asthma in their children at age 1 year and again
      about their child's asthma at age 3 years. Fathers were asked about symptoms of
      posttraumatic stress disorder (PTSD), depression, and antisocial behavior.
      Mothers were asked about depressive symptoms. Outcomes assessed in children
      included recent asthma symptoms, oral steroid use and hospitalizations for asthma
      in the prior year, and asthma diagnosis. Generalized estimated equation models
      were used for the multivariate analysis of parental psychosocial stress and
      asthma morbidity in childhood. RESULTS: After multivariable adjustment, paternal
      PTSD symptoms, depression, and antisocial behavior were each associated with
      increased asthma symptoms at age 1 year (eg, odds ratio, 1.08 for each 1-point
      increase in PTSD score; 95% CI, 1.03-1.14). Maternal depressive symptoms were
      associated with an increased risk of asthma hospitalizations at age 1 year. At
      age 3 years, maternal depressive symptoms were associated with asthma diagnosis
      and hospitalizations for asthma (odds ratio for each 1-point increase in
      symptoms, 1.16; 95% CI, 1.00-1.36). In an analysis combining 1- and 3-year
      outcomes, paternal depression was associated with oral steroid use, maternal
      depressive symptoms were associated with asthma hospitalizations and asthma
      diagnosis, and parental depression was associated with hospitalizations for
      asthma. CONCLUSIONS: Both paternal and maternal psychosocial factors can
      influence asthma morbidity in young Puerto Rican children.

PMID- 21194743
TI  - Investigations on a methacrylate-based flowable composite based on the SDRTM
      technology.
AB  - OBJECTIVE: Monomer development for a reduced shrinkage of composite materials
      still challenges the modern research. The purpose of this study was to analyse
      the shrinkage behavior of an innovative composite material for dental
      restorations based on a resin system that is claimed to control polymerization
      kinetics having incorporated a photoactive group within the resin. METHODS:
      Shrinkage stress development within the first 300s after photoinitiation, gel
      point as well as micro-mechanical properties (Vickers hardness HV, modulus of
      elasticity E, creep Cr and elastic-plastic indentation work W(e)/W(tot)) were
      evaluated (n = 10). The experimental flowable resin-based composite (RBC) was
      measured in comparison to regular methacrylate-based micro- (Esthet X Flow) and
      nano-hybrid flowable RBCs (Filtek Supreme Plus Flow). Additionally, the high
      viscosity counterparts of the two regular flowable methacryate-based composites
      (Esthet X Plus and Filtek Supreme Plus) as well as a low shrinkage silorane-based
      micro-hybrid composite (Filtek Silorane) were considered. The curing time was 20s
      (LED unit Freelight2, 3M-ESPE, 1226 mW/cm(2)). RESULTS: The experimental material
      achieved the significantly lowest contraction stress (1.1 +/- .01 MPa) followed
      by the silorane-based composite (3.6 +/- .03 MPa), whereas the highest stress
      values were induced in the regular methacrylate-based flowable composites EsthetX
      Flow (5.3 +/- .3 MPa) and Filtek Supreme Flow (6.5 +/- .3 MPa). In view of gel
      point, the best values were obtained for the experimental flowable composite (3.1
      +/- .1s) and Filtek Silorane (3.2 +/- .3s), which did not differ significant from
      each others, whereas EsthetX Plus and Filtek Supreme Plus did also not differ
      significantly, inducing the shortest gel point. The experimental flowable
      material achieved also the lowest shrinkage-rate (maximum at 0.1 MPa/s). For all
      analysed materials, no significant difference in the micro-mechanical properties
      between top and bottom were found when measured on 2mm thick increments 24h after
      polymerization. The categories of flowable materials performed in the measured
      micro-mechanical properties significantly inferior when compared to the hybrid
      composites, showing lower HV and E and predominantly higher creep and plastic
      deformation. Within the flowable RBCs, the experimental material achieved the
      lowest Vickers hardness, the highest modulus of elasticity, the highest creep and
      showed the significantly lowest elastic deformation. SIGNIFICANCE: The
      experimental flowable composite revealed the lowest shrinkage stress and
      shrinkage-rate values in comparison to regular methacrylate composites but
      intermediate micro-mechanical properties. Being at the same time more rigid
      (higher modulus of elasticity) and more plastic (low W(e)/W(tot) and high creep
      values) as the regular flowable materials, its effect on interfacial stress build
      up cannot be easily predicted.

PMID- 21194745
TI  - Effect of incorrect interpretation of population statistics in the description of
      coral population dynamics: response to Crabbe 2009.

PMID- 21194746
TI  - A sandwich model for engineering cartilage with acellular cartilage sheets and
      chondrocytes.
AB  - Acellular cartilage can provide a native extracellular matrix for cartilage
      engineering. However, it is difficult for cells to migrate into acellular
      cartilage because of its non-porous structure. The aim of this study is to
      establish a sandwich model for engineering cartilage with acellular cartilage
      sheets and chondrocytes. Cartilage from adult pig ear was cut into a circular
      cylinder with a diameter of approximately 6 mm and freeze-sectioned at
      thicknesses of 10 MUm and 30 MUm. The sheets were then decellularized and
      lyophilized. Chondrocytes isolated from newborn pig ear were expanded for 2
      passages. The acellular sheets and chondrocytes were then stacked layer-by-layer,
      in a sandwich model, and cultured in dishes. After 4 weeks of cultivation, the
      constructs were then either maintained in culture for another 12 weeks or
      implanted subcutaneously in nude mouse. Histological analysis showed that cells
      were completely removed from cartilage sheets after decellularization. By re
      seeding cells and stacking 20 layers of sheets together, a cylinder-shaped cell
      sheet was achieved. Cartilage-like tissues formed after 4 weeks of culture.
      Histological analyses showed the formation of cartilage with a typical lacunar
      structure. Cartilage formation was more efficient with 10 MUm-thick sheets than
      with 30 MUm sheets. Mature cartilage was achieved after 12 weeks of implantation,
      which was demonstrated by histology and confirmed by Safranin O, Toluidine blue
      and anti-type II collagen antibody staining. Furthermore, we achieved cartilage
      with a designed shape by pre-shaping the sheets prior to implantation. These
      results indicate that the sandwich model could be a useful model for engineering
      cartilage in vitro and in vivo.

PMID- 21194747
TI  - Drug permeation across intestinal epithelial cells using porous silicon
      nanoparticles.
AB  - Mesoporous silicon particles hold great potential in improving the solubility of
      otherwise poorly soluble drugs. To effectively translate this feature into the
      clinic, especially via oral or parenteral administration, a thorough
      understanding of the interactions of the micro- and nanosized material with the
      physiological environment during the delivery process is required. In the present
      study, the behaviour of thermally oxidized porous silicon particles of different
      sizes interacting with Caco-2 cells (both non-differentiated and polarized
      monolayers) was investigated in order to establish their fate in a model of
      intestinal epithelial cell barrier. Particle interactions and TNF-alpha were
      measured in RAW 264.7 macrophages, while cell viabilities, reactive oxygen
      species and nitric oxide levels, together with transmission electron microscope
      images of the polarized monolayers, were assessed with both the Caco-2 cells and
      RAW 264.7 macrophages. The results showed a concentration and size dependent
      influence on cell viability and ROS-, NO- and TNF-alpha levels. There was no
      evidence of the porous nanoparticles crossing the Caco-2 cell monolayers, yet
      increased permeation of the loaded poorly soluble drug, griseofulvin, was shown.

PMID- 21194748
TI  - Review: Effects of PPAR activation in the placenta and the fetus: implications in
      maternal diabetes.
AB  - Peroxisome proliferator-activated receptors (PPARalpha, PPARdelta and PPARgamma)
      are ligand-activated transcription factors that regulate metabolic, anti
      inflammatory and developmental processes. The maternal and fetal metabolic
      impairments, the intrauterine pro-inflammatory environment and the developmental
      defects induced by maternal diabetes make PPARs an interesting focus of
      investigation. Therefore, research has been conducted in experimental models of
      diabetes throughout gestation. During embryo organogenesis, impaired PPARdelta
      signaling pathways are related to the induction of congenital malformations. In
      fetuses from diabetic rats, both lipid metabolism and several pro-inflammatory
      markers are regulated by the activation of PPAR isotypes. In the placenta from
      diabetic animals, activation of different PPAR isotypes regulates lipid
      metabolism and anti-inflammatory pathways, whereas in term placentas from
      diabetic patients PPARgamma reduces the production of nitric oxide. Decreased
      PPARgamma and PPARalpha protein expression are found in term placentas of
      diabetic animals and diabetic patients. In addition, a deficiency in
      polyunsaturated fatty acids (PUFAs) and impaired formation of arachidonic acid
      derivatives that activate PPARs is found in several diabetic intrauterine
      tissues. PPARs can be activated by both natural and pharmacological activators.
      Intrauterine activation of PPARs can be achieved by the administration of
      maternal diets enriched in PUFAs. This review summarizes recent advances
      highlighting the possible beneficial role of PPAR activation on embryonic and
      feto-placental development in maternal diabetes.

PMID- 21194749
TI  - Broodstock diet effect on sea urchin Paracentrotus lividus (Lamarck, 1816)
      endotrophic larvae development: potential for their year-round use in
      environmental toxicology assessment.
AB  - The effect of captive broodstock diet on fertilization and endotrophic larvae
      development of the sea urchin Paracentrotus lividus was assessed. Maize grain and
      five inert pelleted diets were tested, during a three-month experimental period.
      Maize flour, wheat flour, soybean flour, maize/wheat flour (MWF) and
      maize/soybean flour mixes were used as vegetal sources for inert feed. Gonad
      index, percent egg fertilization and larvae malformation occurrence were compared
      with the results obtained from wild sea urchins (W). Whole egg total amino acid
      composition was concomitantly analyzed as a tool to explain eventual endotrophic
      larvae malformations caused by lack of specific nutrients. For all treatment
      groups (wild and captive), percent egg fertilization values above 96% were always
      observed, fulfilling the requisites (70-90%) necessary to conduct environmental
      monitoring bioassays, according to USEPA (2002). Similar values for normal
      percent larval development were only obtained from P. lividus broodstock
      subjected to an inert feeding diet based on a maize/wheat flour mix (85.0+/
      1.45%), in comparison to wild P. lividus (82.5+/-1.75%). Likewise, no statistical
      differences on resultant whole egg total amino acid composition were observed
      between P. lividus fed MWF and wild treatments. Moreover, statistical differences
      between MWF and all the other captive feeding treatments were found for six out
      of the seventeen amino acids analyzed. This study demonstrates the possibility to
      obtain high values for P. lividus endotrophic larvae percent normal development
      based on broodstock held in captivity as long as an appropriate inert diet is
      provided.

PMID- 21194750
TI  - Bartonella and Babesia infections in cattle and their ticks in Taiwan.
AB  - Bartonella and Babesia infections and the association with cattle breed and age
      as well as tick species infesting selected cattle herds in Taiwan were
      investigated. Blood samples were collected from 518 dairy cows and 59 beef cattle
      on 14 farms and 415 ticks were collected from these animals or in a field.
      Bartonella and Babesia species were isolated and/or detected in the cattle blood
      samples and from a selected subset (n=254) of the ticks either by culture or DNA
      extraction, PCR testing and DNA sequence analysis. Bartonella bovis was isolated
      from a dairy cow and was detected in 25 (42.4%) beef cattle and 40 (15.7%) tick
      DNA samples. This is the first isolation of B. bovis from cattle in Asia and
      detection of a wide variety of Bartonella species in Rhipicephalus microplus.
      Babesia spp. were detected only on one farm from dairy cows either infected by
      Babesia bovis (n=10, 1.9%) or B. bigemina (n=3, 0.6%).

PMID- 21194751
TI  - New Jersey Children's Behavioral Healthcare System: cross service delivery
      planning for transitional population of youth (ages 16 and 18+ years).
AB  - The continued need for improvement within a 'system of care' is essential as the
      need for mental health services by those 'youth' within the child welfare system
      continually grows. This article outlines the statewide reform of New Jersey's
      Children's Behavioral Healthcare System, which began in 2000, as well as
      including the recommendations of the University of South Florida as part of their
      'Final Report: Independent Assessment of New Jersey's Child Behavioral Health
      Services' on continued changes within the system of care. Successful outcomes
      have resulted from this welfare reform initiative, which include most notably the
      significant caseload decrease of the Division of Youth and Family Services (DYFS)
      and the creation of a new cabinet entity, the Department of Children and Families
      (DCF). This article specifically outlines systemic recommendations to best serve
      the target population of 'transitional' youth between the ages of 16 to 18+ years
      utilizing interagency cooperation based upon 'theory of change' and Total
      Clinical Outcomes Management (TCOM) strategies.

PMID- 21194752
TI  - B cell immunotherapy in autoimmunity--2010 update.
AB  - B cells play important roles in normal immunity and human disease. While much has
      been learned from elegant studies utilizing genetically modified mice or with
      immunotherapy in normal and in autoimmune mice, we are merely at the start of
      learning about the mechanism(s) by which B cells contribute to human autoimmune
      disease. Here, I will review the most recent insights obtained with
      immunomodulatory therapies in human disease highlighting the clinical and
      immunological lessons we have learned with B cell depleting (e.g., rituximab) and
      immunomodulatory (e.g., BAFF/BLys neutralization through belimumab) therapies.

PMID- 21194753
TI  - Preferential targeting of somatic hypermutation to hotspot motifs and
      hypermutable sites and generation of mutational clusters in the IgVH alleles of a
      rheumatoid factor producing lymphoblastoid cell line.
AB  - Epstein-Barr virus transforms human peripheral B cells into lymphoblastoid cell
      lines (LCL) that secrete specific antibodies. Our previous studies showed that a
      monoclonal LCL that secretes a rheumatoid factor expressed activation-induced
      cytidine deaminase (AID) and displayed an ongoing process of somatic
      hypermutation (SHM) at a frequency of 1.7*10-3 mut/bp in its productively
      rearranged IgVH gene. The present work shows that SHM similarly affects the
      nonproductive IgVH allele of the same culture. Sequencing of multiple cDNA clones
      derived from cellular subclones of the parental culture, showed that both alleles
      exhibited an ongoing mutational process with mutation rates of 2-3*10-5
      mut/bp*generation with a high preference for C/G transition mutations and lack of
      a significant strand bias. About 50% of the mutations were targeted to the
      underlined C/G bases in the WRCH/DGYW and RCY/RGY hotspot motifs, indicating that
      they were due to the initial phase of AID activity. Mutations were targeted to
      the VH alleles and not to the CMU or to the GAPDH genes. Genealogical trees
      showed a stepwise accumulation of only 1-3 mutations per branch of the tree.
      Unexpectedly, 27% of all the mutations in the two alleles occurred repeatedly and
      independently within certain sites (not necessarily the canonical hotspot motifs)
      in cellular clones belonging to different branches of the lineage tree.
      Furthermore, some of the mutations seem to arise as recurrent mutational
      clusters, independently generated in different cellular clones. Statistical
      analysis showed that it is very unlikely that these clusters were due to random
      targeting of equally accessible hotspots, indicating the presence of
      'hypermutable sites' that generate recurring mutational clusters in the IgVH
      alleles. Intrinsic hypermutable sites may enhance affinity maturation and
      generation of effective mutated antibody repertoires against invading pathogens.

PMID- 21194754
TI  - Age- and gender-specific prevalence of depression in latest-life--systematic
      review and meta-analysis.
AB  - OBJECTIVE: The objective of the study is to systematically analyze the prevalence
      of depression in latest life (75+), particularly focusing on age- and gender
      specific rates across the latest-life age groups. DESIGN: Relevant articles were
      identified by systematically searching the databases MEDLINE, Web of Science,
      Cochrane Library and Psycinfo and relevant literature from 1999 onwards was
      reviewed. Studies based on the community-based elderly population aged 75 years
      and older were included. Quality of studies was assessed. Meta-analysis was
      performed using random effects model. RESULTS: 24 studies reporting age- and
      gender-specific prevalence of depression were found. 13 studies had a high to
      moderate methodical quality. The prevalence of major depression ranged from 4.6%
      to 9.3%, and that of depressive disorders from 4.5% to 37.4%. Pooled prevalence
      was 7.2% (95% CI 4.4-10.6%) for major depression and 17.1% (95% CI 9.7-26.1%) for
      depressive disorders. Potential sources of high heterogeneity of prevalence were
      study design, sampling strategy, study quality and applied diagnostics of latest
      life depression. CONCLUSIONS: Despite the wide variation in estimates, it is
      evident that latest life depression is common. To reduce variability of study
      results, particularly sampling strategies (inclusion of nursing home residents
      and severe cognitively impaired individuals) for the old age study populations
      should be addressed more thoroughly in future research.

PMID- 21194755
TI  - Effect of 5-HT1A-receptor functional polymorphism on Theory of Mind performances
      in schizophrenia.
AB  - Theory of Mind (ToM) abilities are known to be impaired in schizophrenia and data
      from functional brain imaging studies showed that ToM deficit is correlated to
      prefrontal cortex (PFC) dysfunction. Moreover, several lines of evidence suggest
      a critical role for dopaminergic-serotoninergic interactions at the PFC level. In
      this view, we aimed to analyse the specific effect of the -1019C/G functional
      polymorphism of the serotonin 1A receptor (5-HT1A-R), involved in both serotonin
      and dopamine transmission regulation. A total of 118 clinically stabilised
      schizophrenia patients was assessed with a neuropsychological battery, including
      evaluation of IQ, verbal memory, attention and executive function and a ToM task;
      they also underwent 5-HT1A-R genotyping. We observed a significant effect of the
      5-HT1A-R genotype on ToM performances, with the CC genotype performing
      significantly better. The finding suggests an effect of the 5-HT1A-R polymorphism
      on ToM cognitive performance in schizophrenia patients, probably through complex
      interactions between dopaminergic and serotoninergic systems, involved in
      mentalising.

PMID- 21194756
TI  - Evaluation of cytokine mRNA expression in bronchoalveolar lavage cells from
      horses with inflammatory airway disease.
AB  - Inflammatory airway disease (IAD) is a common disorder of performance horses and
      is associated with poor performance and accumulation of mucus and inflammatory
      cells in lower airway secretions. Horses with IAD frequently have increased
      relative counts of neutrophils in bronchoalveolar lavage fluid (BALF); less
      commonly relative counts of eosinophils and/or mast cells may be increased. The
      aetiopathogenesis of IAD is unknown and may involve innate and/or acquired immune
      responses to various factors including respirable dust constituents, micro
      organisms, noxious gases and unconditioned air. The molecular pathways and role
      of the immune system in the pathogenesis of IAD remain poorly defined and it is
      unknown whether polarised T cell responses occur in the disease, as have been
      reported to occur in equine recurrent airway obstruction and asthma in humans.
      Elucidating cytokine responses that develop in horses with IAD may allow a
      greater understanding of the possible aetiopathological pathway(s) involved and
      could contribute to development of novel treatments. We compared the mRNA
      expression of tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN
      gamma), interleukin (IL)-1beta, IL-2, IL-4, IL-8, IL-13, IL-17 and IL-23 in cell
      pellets extracted from BALF of horses with IAD (n=21) and horses free of
      respiratory tract disease (n=17). Horses with IAD had significantly increased
      levels of TNF-alpha, IL-1beta and IL-23 mRNA; no significant differences in the
      other cytokine mRNAs were detected. The results of this study indicate that IAD
      of horses is associated with increased mRNA expression of pro-inflammatory
      cytokines in BALF cells, which may reflect stimulation of the innate immune
      responses to inhaled antigens. There was no evidence of a polarised T-cell
      cytokine response suggesting hypersensitivity responses may not be involved in
      the aetiopathogenesis of IAD.

PMID- 21194757
TI  - High mortality of older patients admitted to hospital from care homes and insight
      into potential interventions to reduce hospital admissions from care homes: the
      Norfolk experience.
AB  - There is a high mortality rate in patients admitted to hospitals acutely from
      care homes. In a retrospective case analysis study of 3772 older people admitted
      to the Department of Medicine for the Elderly between January and June 2005, 340
      (9.0%) were from care homes, and 93 (27.3%) of the residents died during the
      index admission. Nearly 40% of these deaths occurred within 24h of admission
      indicating a high level of less appropriate admissions. Investigating eight
      nursing homes which admitted the highest number of patients from one primary care
      trust revealed that the most cited reasons for admission were the lack of advance
      care plans, access to General Practitioners (GPs) out of hours, as well as
      general access to palliative care and specialist nurses, and poor communication
      between patient, relatives, GPs, hospitals and care home staff. Our findings
      provide some useful insight into the factors that need to be addressed to avoid
      unnecessary or inappropriate admissions from care homes for better end of life
      care in aging societies.

PMID- 21194759
TI  - Bone mineral density: a potential determinant of atherosclerotic plaque
      morphology in established coronary artery disease?

PMID- 21194758
TI  - How family support affects physical activity (PA) among middle-aged and elderly
      people before and after they suffer from chronic diseases.
AB  - The more support elderly people have from their family, the less likely they are
      to suffer from chronic diseases. The objective of this study is to investigate
      how family support affects the PA middle-aged and elderly people engage in before
      and after they suffer from chronic diseases. We interviewed 428 middle-aged and
      elderly people using a structured questionnaire to measure their aerobic PA.
      Eighteen percent of middle-aged and elderly people did participate in PA after
      suffering from chronic diseases. Using multivariate logistic regression models,
      we found that middle-aged and elderly people who rely on family members when they
      are sick (OR=1.87, 95%CI=1.08-3.25) and who are accompanied by family members
      (OR=2.09, 95%CI=1.20-3.62) when they are healthy are more likely to exercise. The
      more middle-aged and elderly people are supported by their family, the more
      likely they are to exercise. Strengthening family relationships should help
      reduce the prevalence of chronic diseases among middle-aged and elderly people.

PMID- 21194760
TI  - Brachial artery flow mediated assessment: a tool to predict the response to
      chronic PDE5 inhibition with tadalafil in patients with erectile dysfunction.

PMID- 21194761
TI  - Circadian variation in coronary flow velocity reserve and its relation to alpha1
      sympathetic activity in humans.
AB  - BACKGROUND: The circadian change in coronary microvascular function has not been
      directly assessed in human beings. Recent advances in transthoracic Doppler
      echocardiography (TTDE) provide noninvasive, physiological assessment of coronary
      flow velocity reserve (CFVR). METHODS: This study consisted of 20 young healthy
      subjects (24 +/- 2 years, 20 men) who underwent CFVR examinations at 3 different
      times; early morning (6AM), late morning (11AM) and late evening (10PM). The flow
      velocity in the distal portion of the left anterior descending coronary artery
      was measured with TTDE at baseline and during adenosine infusion to calculate
      CFVR. These examinations were repeated with the intake of alpha1-blocker
      (prazosin 1mg) on the other day. RESULTS: CFVR showed a circadian variation with
      an increase from the early morning to the late morning, following a decrease to
      the late evening thereafter (4.4 +/- 0.9 at 6AM; 5.2 +/- 1.3 at 11AM; 4.2 +/- 1.1
      at 10PM, p<0.001). In the study with alpha1-blocker, CFVR was comparable between
      the early morning and the late morning, whereas CFVR in the late evening was
      lower than those in other 2 time points (5.0 +/- 1.1 at 6AM; 4.9 +/- 0.9 at 11AM;
      4.3 +/- 0.9 at 10PM, p<0.001). CONCLUSIONS: This study demonstrates that CFVR has
      a circadian variation in humans, with an increase from the late evening to the
      late morning. Adding alpha1-blocker ameliorated CFVR only in the early morning,
      indicating that alpha1-sympathetic activity plays a heterogeneous and important
      role in the circadian change of CFVR in humans.

PMID- 21194762
TI  - Risk of bleeding after prehospital administration of high dose tirofiban for ST
      elevation myocardial infarction.
AB  - BACKGROUND: In most patients with ST-elevation myocardial infarction (STEMI),
      antiplatelet drugs are already administrated in the ambulance, before hospital
      admission. We investigated the safety of prehospital initiation of a high dose of
      the glycoprotein IIb/IIIa inhibitor tirofiban on top of aspirin, clopidogrel and
      heparin. METHODS: It concerns a sub-analysis of the On-TIME 2 trial. 1398
      patients were enrolled and 1275 patients (91.2%) had clinical follow up. Non CABG
      related bleeding was defined according to the TIMI criteria. Logistic regression
      was used to determine predictors of 30-day bleeding. The independent association
      between bleeding and mortality (30-day and 1-year) was evaluated using Cox
      proportional Hazard models. RESULTS: Bleeding (major or minor) was observed in 47
      patients (3.7%), with only 13 patients (1%) with major bleeding. The strongest
      independent determinants of bleeding were age (OR 1.05, 95% CI 1.01-1.08,
      p=0.011), Killip class >1 at admission (OR 2.5, 95% CI 1.2-5.3, p=0.020) and
      intra aortic balloon pump (IABP) use (OR 4.2, 95% CI 1.6-11.1, p=0.003). High
      dose tirofiban was not an independent predictor of bleeding (OR 1.7, 95% CI 0.9
      3.2, p=0.116). Bleeding was associated with an increased risk of 30-day mortality
      (HR 5.5, 95% CI 1.6-7.8, p<0.001) and one-year mortality (HR 3.2, 95% CI 1.4-7.2,
      p=0.005). CONCLUSION: Prehospital use of high dose tirofiban is safe and
      associated with a low risk of bleeding. Age, Killip class >1, IABP use, but not
      high dose tirofiban are independent determinants of bleeding in STEMI patients.
      Bleeding is independently associated with 30-day and 1-year mortality.

PMID- 21194763
TI  - Diagnosis of IgG4-related systemic disease by cytology of large pericardial
      effusion with fine needle aspiration.

PMID- 21194764
TI  - Mitral annular longitudinal function preservation after mitral valve repair: the
      MARTE study.
AB  - BACKGROUND: In patients with chronic mitral regurgitation (MR), undergoing
      surgical mitral valve repair, current Guidelines only recommend standard
      echocardiographic indices i.e. left ventricular (LV) ejection fraction (EF), and
      LV end-systolic and end-diastolic diameters as preoperative variables. However LV
      EF is often preserved until advanced stages of the valve disease. Aim of this
      study was to evaluate changes in LV systolic longitudinal function, 3 months
      after mitral valve repair in patients with chronic degenerative MR and normal
      preoperative EF. METHODS: We measured M-mode mitral lateral annulus systolic
      excursion (MAPSE) and Tissue Doppler (TD) peak systolic annular velocity (S(m))
      in 31 patients with moderate to severe MR and normal EF (59.9 +/- 4.7%)
      candidates for mitral valve repair, preoperatively and 3 months after surgery.
      RESULTS: After mitral valve repair, S(m) increased from 7.8 +/- 1.4 to 9.6 +/-
      2.2 cm/s (p<0.0001) and MAPSE increased from 1.33 +/- 0.26 to 1.55 +/- 0.25 cm
      (p=0.0013). EF decreased from 59.9 +/- 4.7 to 51.3 +/- 5.9% (p<0.0001). As
      expected, LV diameters and volumes, wall thicknesses, midwall fractional
      shortening (mFS), and left atrial (LA) size were all reduced after surgery.
      CONCLUSIONS: This study suggests that assessment of LV long axis systolic
      velocity and amplitude of excursion by echocardiography is more sensitive than
      simple determination of EF for revealing the beneficial impact of MR surgery on
      overall systolic function.

PMID- 21194765
TI  - Risk estimation approach in Chagas disease is still needed.

PMID- 21194766
TI  - The N-terminal pro-B-type natriuretic peptide as a predictor of disease
      progression in patients with pericardial effusion.
AB  - BACKGROUND: The purpose of this study was to evaluate the value of N-terminal pro
      B-type natriuretic peptide (NT-proBNP) as a predictor of disease progression in
      patients with pericardial effusions (PE). METHOD: We retrospectively studied
      consecutive patients that had moderate or large PEs. Patients with pericardial
      events, such as reaccumulation of PE, persistent drainage through a catheter
      longer than one week, or newly developed constrictive pericarditis were defined
      as the progression group (Group A), and patients without these findings were
      defined as the group with no progression (Group B). The NT-proBNP assay was
      performed when PE was detected. RESULTS: Compared to Group B (27 patients), Group
      A (15 patients) exhibited lower systolic and diastolic blood pressures (106 +/-
      13 vs. 118 +/- 19 mm Hg, p=0.028; 69 +/- 9 vs. 75 +/- 11 mm Hg, p=0.047), higher
      NT-proBNP levels (1063 +/- 756 vs. 578 +/- 1090 ng/L, p=0.002), larger inferior
      vena cava (21 +/- 6 vs. 17 +/- 5 mm, p=0.039) and higher estimated right
      ventricular systolic pressure (37 +/- 5 vs. 32 +/- 6 mm Hg, p=0.024). NT-proBNP
      was the only independent predictor of disease progression (p=0.034) by
      multivariate regression analysis. The receiver-operating characteristic curve
      analysis showed that NT-proBNP values >= 548 ng/L demonstrated a sensitivity of
      80% and a specificity of 78% for identifying disease progression (p=0.001).
      CONCLUSIONS: The NT-proBNP value may predict disease progression in patients with
      PE. However, additional prospective studies with more patients are needed.

PMID- 21194767
TI  - Significant intimal hyperplasia regression between 6 and 18 months following
      GenousTM endothelial progenitor cell capturing stent placement.

PMID- 21194768
TI  - 99mTc-MAA lung scan can be an alternative in detection and follow-up of patent
      foramen ovale.

PMID- 21194769
TI  - Increased platelet residual activity in patients treated with acetosalicylic acid
      is associated with increased tissue factor and decreased tissue factor pathway
      inhibitor plasma levels.

PMID- 21194770
TI  - Delays in diagnostics and treatment of cardiac tumors are unacceptable.

PMID- 21194771
TI  - Angiotensin-(1-7): a new therapeutic strategy in the management of atrial
      fibrillation.

PMID- 21194772
TI  - High risk closure of a large secundum ASD causing platypnea-orthodeoxia.

PMID- 21194773
TI  - A patient with moderate hypertriglyceridemia resistant to omega-3 fatty acid.

PMID- 21194774
TI  - Takotsubo syndrome associated with seizures: an underestimated cause of sudden
      death in epilepsy?

PMID- 21194775
TI  - Additive hypoglycaemic effect of nateglinide and exogenous glucagon-like peptide
      1 in type 2 diabetes.
AB  - We examined the postprandial glucose regulators nateglinide and GLP-1, separately
      and in combination, in people with type 2 diabetes. Nateglinide inhibited DPP-4
      activity, reduced GLP-1 degradation and enhanced its insulinotropic and blood
      glucose lowering effect. Combining nateglinide and GLP-1 derivatives may
      effectively control postprandial glycaemia.

PMID- 21194776
TI  - Analysis of a primary care led diabetes annual review programme in a multi ethnic
      cohort in Wellington, New Zealand.
AB  - INTRODUCTION: In 2000 a primary care led "Get Checked" programme of free annual
      diabetes reviews was introduced in New Zealand. This report explores changes in
      clinical variables over five annual visits in relation to ethnicity. METHODS:
      From 19,054 people in the Wellington region all 2967 with Type 2 diabetes
      completing five visits between 2000 and 2006 contributed data. This included
      weight, blood pressure, HbA1c, lipids, and urinary albumin:creatinine ratio.
      Mixed linear models examined changes in clinical variables by visit and the
      relationships with ethnicity. RESULTS: Of the 2967, 69.5% were European, 10.0%
      Maori, 8.6% Pacific and 10.4% Asian. Weight, systolic and diastolic blood
      pressure declined. HbA1c initially declined with time in Maori, Pacific and Asian
      and then rose. Total cholesterol decreased and HDL cholesterol rose. Urinary
      albumin:creatinine ratio fell at first and then rose and the degree of change was
      dependent on ethnicity. Use of diabetes medications and ACE inhibitor
      prescription increased in all ethnicities. Statin prescriptions rose from 20 to
      61%. Current smoking rates fell from 10.7% to 9.4%. CONCLUSION: This programme
      showed improvements in intermediate outcomes of diabetes care across all ethnic
      groups highlighting the benefit of reducing barriers to, and increasing
      engagement with, good primary health care.

PMID- 21194777
TI  - Contrasting cardiovascular risk profiles and prescribed cardio-protective
      therapies in newly-diagnosed type 2 diabetes identified through screening and
      standard practice.
AB  - AIMS: Screening for Type 2 diabetes mellitus (T2DM) may improve long-term
      outcomes by managing cardiovascular risk at an earlier stage of the disease. The
      cardiovascular risk profile of screen-detected (SD) T2DM is ill defined and has
      not been compared to conventional newly diagnosed (CD) cases. METHODS: Baseline
      data from SD (n=337) and CD (n=824) cohorts were compared. SD adopted mixed
      approaches to screening, population based (n=214) and cardiovascular-risk factor
      targeted (n=123). CD reflected UK primary care practice with cases referred
      within four weeks of diagnosis. RESULTS: People with SD T2DM were leaner, had a
      lower HbA1c(%) and lower triglyceride but were more hypertensive compared to
      people with CD T2DM. Fewer SD were on blood pressure lowering (46% vs. 60%,
      p<0.0001), statin (30% vs. 41%, p<0.0001) or anti-platelet (15% vs. 27%,
      p<0.0001) therapies. Modelled 10 year cardiovascular disease (CVD) risk was
      actually greater in the SD group compared to CD (CVD: 20.8 vs. 17.2, p=0.0001).
      CONCLUSION: Individuals with SD T2DM are at high risk of CVD as a result of
      untreated hyperglycaemia, hypertension and dyslipidaemia. Those prescribed
      antihypertensive or lipid-lowering therapies frequently still had inadequate
      control. Identifying vascular risk by screening for latent glucose disease
      provides therapeutic opportunities for earlier intervention.

PMID- 21194778
TI  - From evidence to practice--the IMAGE project--new standards in the prevention of
      type 2 diabetes.

PMID- 21194779
TI  - Factors associated with the maintenance or achievement of the weight loss goal at
      follow-up among participants completing an adapted diabetes prevention program.
AB  - AIMS: This study evaluated factors associated with achievement or maintenance of
      a 7% weight loss goal post intervention among adults at high-risk for
      cardiovascular disease (CVD) and diabetes who participated in an adapted Diabetes
      Prevention Program (DPP) intervention. MATERIALS AND METHODS: High-risk adults
      completed the intervention in 2008 or 2009 (N=466). In 2010, we conducted a
      follow-up survey of participants to assess characteristics, behaviors and
      barriers associated with the maintenance or achievement of the weight loss goal.
      RESULTS: Thirty-nine percent of respondents (73/188) maintained or achieved the
      goal post intervention. Participants who achieved the goal were more likely to
      have attended more intervention sessions, and to have lost more weight during the
      intervention compared to participants who did not achieve the goal. Participants
      who achieved or maintained the goal post intervention were more likely to engage
      in behaviors related to weight loss maintenance. DISCUSSION: Our findings suggest
      maintenance or achievement of a weight loss goal post intervention among
      participants in an adapted lifestyle intervention is consistent with the original
      DPP. Our findings also highlight the relationship between maintaining or
      achieving a weight loss goal post intervention and behaviors that can be
      reinforced and barriers that can be mitigated.

PMID- 21194780
TI  - Health policy processes in maternal health: a comparison of Vietnam, India and
      China.
AB  - This article reports on a comparative analysis to assess and explain the
      strengths and weaknesses of policy processes based on 9 case-studies of maternal
      health in Vietnam, India and China. Policy processes are often slow, inadequately
      coordinated and opaque to outsiders. Use of evidence is variable and, in
      particular, could be more actively used to assess different policy options.
      Whilst an increasing range of actors are involved, there is scope for further
      opening up of the policy processes. This is likely, if appropriately managed with
      due regard to issues such as accountability of advocacy organisations, to lead to
      stronger policy development and greater subsequent ownership; it may however be a
      more messy process to co-ordinate. Coordination is critical where policy issues
      span conventional sectoral boundaries, but is also essential to ensure
      development of policy considers critical health system and resource issues. This,
      and other features related to the nature of a specific policy issue, suggests the
      need both to adapt processes for each particular policy issue and to monitor the
      progress of the policy processes themselves. The article concludes with specific
      questions to be considered by actors keen to enhance policy processes.

PMID- 21194781
TI  - Improved biliary detection and diagnosis through intelligent machine analysis.
AB  - This paper reports on work undertaken to improve automated detection of bile
      ducts in magnetic resonance cholangiopancreatography (MRCP) images, with the
      objective of conducting preliminary classification of the images for diagnosis.
      The proposed I-BDeDIMA (Improved Biliary Detection and Diagnosis through
      Intelligent Machine Analysis) scheme is a multi-stage framework consisting of
      successive phases of image normalization, denoising, structure identification,
      object labeling, feature selection and disease classification. A combination of
      multiresolution wavelet, dynamic intensity thresholding, segment-based region
      growing, region elimination, statistical analysis and neural networks, is used in
      this framework to achieve good structure detection and preliminary diagnosis.
      Tests conducted on over 200 clinical images with known diagnosis have shown
      promising results of over 90% accuracy. The scheme outperforms related work in
      the literature, making it a viable framework for computer-aided diagnosis of
      biliary diseases.

PMID- 21194782
TI  - Effect of missing RR-interval data on nonlinear heart rate variability analysis.
AB  - The effects of missing RR-interval data on nonlinear heart rate variability (HRV)
      analysis were investigated using simulated missing data in actual RR-interval
      tachograms and actual missing RR-interval data. For the simulation study,
      randomly selected data (ranging from 0 to 100s) were removed from actual data in
      the MIT-BIH normal sinus rhythm RR-interval database. The selected data are
      considered as a simulated artefact section. In all, 7182 tachograms of 5-min
      duration were used for this analysis. For each missing interval, the analysis was
      performed by 100 Monte Carlo runs. Poincare plot, detrended fluctuation, and
      entropy analysis were executed for the nonlinear HRV parameters in each run, and
      the normalized errors between the data with and without the missing data duration
      for these parameters, were calculated. In this process, the usefulness of
      reconstruction was considered, for which bootstrapping and several interpolation
      methods (nearest neighbour, linear, cubic spline, and piecewise cubic Hermite)
      were used. The rules for the reconstruction, derived from the results of these
      simulations, were evaluated with actual missing RR-interval data obtained from a
      capacitive-coupled ECG during sleep. In conclusion, nonlinear parameters,
      excepting Poincare-plot-analysis parameters, may not be appropriate for the
      accurate HRV analysis with missing data, since these parameters have relatively
      larger error values than time- or frequency-domain HRV parameters. However, the
      analysis of the long-term variation for nonlinear HRV values can be available
      through applying the rules for the reconstruction obtained in this study.

PMID- 21194783
TI  - Multiresolution MUAPs decomposition and SVM-based analysis in the classification
      of neuromuscular disorders.
AB  - This paper describes a new method for the classification of neuromuscular
      disorders based on the analysis of scalograms determined by the Symlet 4 wavelet
      technique. The approach involves isolating single motor unit action potentials
      (MUAPs), computing their scalograms, taking the maximum values of the scalograms
      in five selected scales, and averaging across MUAPs to give a single 5
      dimensional feature vector per subject. After SVM analysis, the vector is reduced
      to a single decision parameter, called the Wavelet Index, allowing the subject to
      be assigned to one of three groups: myogenic, neurogenic or normal. The software
      implementation of the method described above created a tool supporting
      electromyographic (EMG) examinations. The method is characterized by a high
      probability for the accurate diagnosis of muscle state. The method produced 5
      misclassifications out of 800 examined cases (total error of 0.6%).

PMID- 21194784
TI  - An attribute weight assignment and particle swarm optimization algorithm for
      medical database classifications.
AB  - In this research, a hybrid model is developed by integrating a case-based
      reasoning approach and a particle swarm optimization model for medical data
      classification. Two data sets from UCI Machine Learning Repository, i.e., Liver
      Disorders Data Set and Breast Cancer Wisconsin (Diagnosis), are employed for
      benchmark test. Initially a case-based reasoning method is applied to preprocess
      the data set thus a weight vector for each feature is derived. A particle swarm
      optimization model is then applied to construct a decision-making system for
      diseases identified. The PSO algorithm starts by partitioning the data set into a
      relatively large number of clusters to reduce the effects of initial conditions
      and then reducing the number of clusters into two. The average forecasting
      accuracy for breast cancer of CBRPSO model is 97.4% and for liver disorders is
      76.8%. The proposed case-based particle swarm optimization model is able to
      produce more accurate and comprehensible results for medical experts in medical
      diagnosis.

PMID- 21194786
TI  - Consistent interpretation of the results of through-, out-diffusion and tracer
      profile analysis for trace anion diffusion in compacted montmorillonite.
AB  - Literature data for anion diffusion in compacted swelling clays contain
      systematic inconsistencies when the results of through-diffusion tests are
      compared with those of out-diffusion or tracer profile analysis. In the present
      work we investigated whether these inconsistencies can be explained by taking
      into account heterogeneities in the compacted samples; in particular increased
      porosities at the clay boundaries. Based on the combined results of out
      diffusion, tracer profile analysis and the spatial distribution of the
      electrolyte anion in the clay, we conclude that the inconsistencies can indeed be
      resolved by taking into account a heterogeneous distribution of the total and the
      anion-accessible porosity. This, by definition, leads to a position dependence of
      the effective diffusion coefficient. Neglecting these effects results in a rather
      subordinate systematic error in the determination of effective diffusion
      coefficients of anions from through-diffusion tests with clay thicknesses in the
      centimetre range. However, stronger errors in terms of absolute values and
      conceptual interpretation may be introduced in out-diffusion tests and profile
      analyses of the diffused tracer. We recommend that anion diffusion tests should
      be accompanied by measurements of the total and anion-accessible porosity as a
      function of position in the direction of diffusion.

PMID- 21194787
TI  - The "A Disintegrin And Metalloproteases" ADAM10 and ADAM17: novel drug targets
      with therapeutic potential?
AB  - Proteolytic ectodomain release, a process known as "shedding", has been
      recognised as a key mechanism for regulating the function of a diversity of cell
      surface proteins. A Disintegrin And Metalloproteinases (ADAMs) have emerged as
      the major proteinase family that mediates ectodomain shedding. Dysregulation of
      ectodomain shedding is associated with autoimmune and cardiovascular diseases,
      neurodegeneration, infection, inflammation and cancer. Therefore, ADAMs are
      increasingly regarded as attractive targets for novel therapies. ADAM10 and its
      close relative ADAM17 (TNF-alpha converting enzyme (TACE)) have been studied in
      particular in the context of ectodomain shedding and have been demonstrated as
      key molecules in most of the shedding events characterised to date. Whereas the
      level of expression of ADAM10 may be of importance in cancer and
      neurodegenerative disorders, ADAM17 mainly coordinates pro- and anti-inflammatory
      activities during immune response. Despite the high therapeutical potential of
      ADAM inhibition, all clinical trials using broad-spectrum metalloprotease
      inhibitors have failed so far. This review will cover the emerging roles of both
      ADAM10 and ADAM17 in the regulation of major physiological and developmental
      pathways and will discuss the suitability of specifically modulating the
      activities of both proteases as a feasible way to inhibit inflammatory states,
      cancer and neurodegeneration.

PMID- 21194790
TI  - Evaluation of the national campaign to improve hand hygiene in nursing homes in
      Norway.

PMID- 21194788
TI  - Carboxylate metabolism in sugar beet plants grown with excess Zn.
AB  - The effects of Zn excess on carboxylate metabolism were investigated in sugar
      beet (Beta vulgaris L.) plants grown hydroponically in a growth chamber. Root
      extracts of plants grown with 50 or 100MUM Zn in the nutrient solution showed
      increases in several enzymatic activities related to organic acid metabolism,
      including citrate synthase and phosphoenolpyruvate carboxylase, when compared to
      activities in control root extracts. Root citric and malic acid concentrations
      increased in plants grown with 100MUM Zn, but not in plants grown with 50MUM Zn.
      In the xylem sap, plants grown with 50 and 100MUM Zn showed increases in the
      concentrations of citrate and malate compared to the controls. Leaves of plants
      grown with 50 or 100MUM Zn showed increases in the concentrations of citric and
      malic acid and in the activities of citrate synthase and fumarase. Leaf
      isocitrate dehydrogenase increased only in plants grown with 50MUM Zn when
      compared to the controls. In plants grown with 300MUM Zn, the only enzyme showing
      activity increases in root extracts was citrate synthase, whereas the activities
      of other enzymes decreased compared to the controls, and root citrate
      concentrations increased. In the 300MUM Zn-grown plants, the xylem concentrations
      of citric and malic acids were higher than those of controls, whereas in leaf
      extracts the activity of fumarase increased markedly, and the leaf citric acid
      concentration was higher than in the controls. Based on our data, a metabolic
      model of the carboxylate metabolism in sugar beet plants grown under Zn excess is
      proposed.

PMID- 21194789
TI  - Effectiveness of a new decolonisation regimen for eradication of extended
      spectrum beta-lactamase-producing Enterobacteriaceae.
AB  - Gram-negative bacteria expressing extended-spectrum beta-lactamases (ESBL) have
      emerged worldwide. ESBL colonisation can persist for years and may favour ESBL
      transmission. Interventions include contact isolation precautions and restriction
      of antibiotic use, but decolonisation (DC) for ESBL is not established. We
      performed a prospective controlled open-label cohort-study from 1/2000 to 1/2008
      to determine the effectiveness of a standardised DC programme. ESBL-positive
      patients routinely underwent screening from rectum, throat, and urine. DC
      included: chlorhexidine 0.2% mouth rinse three times daily (throat colonisation),
      paromomycin 4 * 1 g daily (intestinal colonisation), and oral antibiotics for
      urinary tract colonisation. ESBL elimination was defined as >= 1 set of negative
      follow-up screenings (throat, rectal, urine). Of 100 enrolled patients, 83% of
      patients were infected and 17% colonised with ESBL. Escherichia coli (71%) and
      Klebsiella pneumoniae (25%) were the most frequent pathogens. Overall, 76%
      (76/100) of patients became negative for ESBL at follow-up. Fifty-five percent
      (42/76) of the successfully treated patients received systemic treatment for
      infection. Of those who completed DC, 83% (15/18) were free of ESBL at follow-up.
      DC success correlated with the number of risk factors and colonised sites. DC may
      be beneficial in a selected group of patients, potentially shortening duration of
      ESBL colonisation and subsequently reducing the risk for transmission.

PMID- 21194791
TI  - Skin antiseptics in venous puncture-site disinfection for prevention of blood
      culture contamination: systematic review with meta-analysis.
AB  - Blood cultures drawn by venous puncture are common clinical procedures for the
      detection of bacteraemia. Blood culture contamination (BCC) can lead to clinical
      misinterpretation and unnecessary expenses. We aimed to systematically review
      randomised controlled trials (RCTs) with skin antiseptics for prevention of
      contamination in venous-puncture drawn blood cultures. We conducted database
      search using CENTRAL (Cochrane Library issue April 2010), MEDLINE, EMBASE and
      mRCT, in June 2010. All RCTs testing skin antiseptics in venous-puncture drawn
      blood cultures were retrieved. Relative risk (RR) of the BCC outcome was analysed
      by random effects method using confidence interval (CI) of 95%. Studies were
      assessed by one review author and checked by another. Six studies were
      identified. Single-trial comparisons showed that alcoholic iodine tincture was
      better than non-alcoholic povidone-iodine, and isopropyl/acetone/povidone-iodine
      showed superiority against isopropyl/povidone-iodine. Meta-analysis demonstrated
      that alcoholic chlorhexidine was better than non-alcoholic povidone-iodine (RR:
      0.33; 95% CI: 0.24-0.46) in 4757 blood cultures from two trials. Alcoholic
      solutions were better than non-alcoholic products (0.53; 0.31-0.90) in 21,300
      blood cultures from four studies. Two trials with 13,418 blood cultures showed
      that iodine tincture was not superior to povidone-iodine in BCC prevention (0.79;
      0.54-1.18). Alcoholic iodine was not different from non-alcoholic iodine (0.79;
      0.53-1.17). Comparison of chlorhexidine vs iodine compounds was not conclusive.
      Alcohol alone was not inferior to iodinated products for prevention of
      contamination in venous-puncture drawn blood cultures. The association of alcohol
      and povidone-iodine did not seem to be useful. Alcoholic chlorhexidine solutions
      reduced blood culture false positives compared with aqueous povidone-iodine.

PMID- 21194792
TI  - Regulation of sporicides under the European Biocidal Products Directive.
AB  - Disinfectants (including sporicides) used in the healthcare setting fall within
      the scope of the European Biocidal Products Directive (98/8/EC). The active
      substances used in these products will be evaluated as part of an EU wide review
      programme, to determine whether they can be used in biocidal products without
      undue risks to humans, animals and the environment, and that these products will
      be effective. Following the review of an active substance, biocidal products
      containing the active substance will become subject to regulatory controls in all
      EU Member States. This paper discusses how the Directive operates, both through
      the review programme and the authorisation of biocidal products at the Member
      State level, together with the requirements to provide data on the efficacy of
      both the active substances and end-use biocidal products.

PMID- 21194793
TI  - Influence of methylation on the antibacterial properties of triclosan in
      Pasteurella multocida and Pseudomonas aeruginosa variant strains.
AB  - The opportunistic bacterium Pasteurella multocida is extremely susceptible to the
      hydrophobic biocide triclosan by virtue of its markedly permeable outer membrane,
      while the nosocomial pathogen Pseudomonas aeruginosa is intrinsically resistant
      to levels far exceeding the triclosan aqueous solubility limit. Widespread
      incorporation of triclosan in health and personal care products has resulted in
      its concomitant accumulation with metabolites such as methyl triclosan in
      environmental and biological systems. The present study was undertaken to
      investigate the possibility that methylation of triclosan may mitigate its
      antiseptic efficacy in healthcare settings, as well as represent a potential
      resistance mechanism. Comparative standardised disc agar diffusion and batch
      cultural turbidimetric bioassays were employed to assess the relationship between
      triclosan-susceptible or -resistant bacteria and methyl triclosan. A wild-type P.
      aeruginosa parental strain and a mutant exhibiting a permeable outer cell
      envelope phenotype were examined in concert with a refractory wild-type strain
      sensitised to triclosan susceptibility using outer membrane permeabiliser
      compound 48/80. All organisms examined were resistant to methyl triclosan, and
      all organisms excluding P. aeruginosa were susceptible to triclosan over a wide
      concentration range. The permeable outer membrane phenotype in both mutant and
      chemically sensitised wild-type strains rendered P. aeruginosa susceptible to
      triclosan, but not to methyl triclosan. These data support the notion that
      methylation of triclosan renders the compound unable to inhibit the growth of
      disparate bacterial pathogens in a manner independent of an intact outer
      membrane. It can also be concluded that biocide modification may contribute to
      the intrinsic resistance of P. aeruginosa to triclosan.

PMID- 21194794
TI  - Cost-analysis of an intensive care unit closure due to an imipenem-resistant oxa
      23 Acinetobacter baumannii outbreak.

PMID- 21194795
TI  - Outbreak of Serratia marcescens infection due to contamination of multiple-dose
      vial of heparin-saline solution used to flush deep venous catheters or peripheral
      trocars.

PMID- 21194796
TI  - Observing and quantifying airflows in the infection control of aerosol- and
      airborne-transmitted diseases: an overview of approaches.
AB  - With concerns about the potential for the aerosol and airborne transmission of
      infectious agents, particularly influenza, more attention is being focused on the
      effectiveness of infection control procedures to prevent hospital-acquired
      infections by this route. More recently a number of different techniques have
      been applied to examine the temporal-spatial information about the airflow
      patterns and the movement of related, suspended material within this air in a
      hospital setting. Closer collaboration with engineers has allowed clinical
      microbiologists, virologists and infection control teams to assess the
      effectiveness of hospital isolation and ventilation facilities. The
      characteristics of human respiratory activities have also been investigated using
      some familiar engineering techniques. Such studies aim to enhance the
      effectiveness of such preventive measures and have included experiments with
      human-like mannequins using various tracer gas/particle techniques, real human
      volunteers with real-time non-invasive Schlieren imaging, numerical modelling
      using computational fluid dynamics, and small scale physical analogues with
      water. This article outlines each of these techniques in a non-technical manner,
      suitable for a clinical readership without specialist airflow or engineering
      knowledge.

PMID- 21194797
TI  - MRI is a sensitive marker of subtle white matter pathology in hypoperfused mice.
AB  - White matter (WM) abnormalities, possibly resulting from hypoperfusion, are key
      features of the aging human brain. It is unclear, however, whether in vivo
      magnetic resonance imaging (MRI) approaches, such as diffusion tensor and
      magnetization transfer MRI are sufficiently sensitive to detect subtle
      alterations to WM integrity in mouse models developed to study the aging brain.
      We therefore investigated the use of diffusion tensor and magnetization transfer
      MRI to measure structural changes in 4 WM tracts following 1 month of moderate
      hypoperfusion, which results in diffuse WM pathology in C57Bl/6J mice. Following
      MRI, brains were processed for evaluation of white and gray matter pathology.
      Significant reductions in fractional anisotropy were observed in the corpus
      callosum (p = 0.001) and internal capsule (p = 0.016), and significant decreases
      in magnetization transfer ratio were observed in the corpus callosum (p = 0.023),
      fimbria (p = 0.032), internal capsule (p = 0.046) and optic tract (p = 0.047)
      following hypoperfusion. Hypoperfused mice demonstrated diffuse axonal and myelin
      pathology which was essentially absent in control mice. Both fractional
      anisotropy and magnetization transfer ratio correlate with markers of myelin
      integrity/degradation and not axonal pathology. The study demonstrates that in
      vivo MRI is a sensitive measure of diffuse, subtle WM changes in the murine
      brain.

PMID- 21194798
TI  - Telomere length and aging biomarkers in 70-year-olds: the Lothian Birth Cohort
      1936.
AB  - Telomeres are nucleo-protein complexes at the end of eukaryotic chromosomes. They
      shorten each time a somatic cell replicates and this shortening is modulated by
      the effects of oxidative stress. Previous studies have associated telomere length
      with a number of age-related outcomes and it is hypothesized to be a quantitative
      indicator of aging. We tested this hypothesis in a cohort of ~1000 relatively
      healthy 70-year-old Scots (the Lothian Birth Cohort of 1936: LBC1936) on whom we
      have measures of cognition, physical health and associated traits, and social
      class. Telomeres were significantly longer in males than females (p < 0.0001).
      Longer telomeres were associated, in females only, with higher general cognitive
      ability scores (p = 0.022) and lower C-reactive protein levels (p = 0.014).
      Telomere length was not associated with any of the other measured cognitive,
      physical, or social traits. In conclusion we find little evidence that telomere
      length is a significant biomarker of normal aging in important cognitive and
      physical domains.

PMID- 21194799
TI  - White matter deterioration in 15 months: latent growth curve models in healthy
      adults.
AB  - The goal of the study was to examine the differences in trajectories of change in
      the volume of white matter hyperintensities (WMH) in healthy adults within a
      relatively short period. We measured volumes of periventricular and deep WMH in
      frontal, temporal, parietal, and occipital lobes of healthy volunteers (age 49
      83) on 3 occasions, approximately 15 months apart. At baseline, 40 participants
      underwent magnetic resonance imaging (MRI), 37 returned for the first and 30 for
      the second follow-up. Latent growth curve models estimated the variance and mean
      change in WMH volume and examined their associations with age, sex, education,
      and hypertension. In both regions and for both WMH types, the positive
      association between volume and age was stronger among the middle-aged adults and
      became weaker in older ages, as a logarithmic function of age. Individual
      variations were present in initial WMH volume but not in WMH volume progression.
      Frontal deep WMH volume was greater in hypertensive participants, whereas lower
      education was associated with greater posterior deep WMH volume. Thus, white
      matter of healthy middle-aged and older adults undergoes significant regional
      deterioration in a relatively short period, and is negatively affected by
      vascular risk and lower educational level.

PMID- 21194800
TI  - [Gunshot wound].

PMID- 21194801
TI  - [End of life decisions, the Dutch form through Spanish eyes].
AB  - Abroad, but also in The Netherlands, there are many misunderstandings concerning
      end of life decisions and euthanasia. In general, euthanasia does not play any
      role in the intensive care units, simply because it does not fulfill the
      conditions to carry it out. However, there is still confusion, merely due to the
      assumption that the Dutch situation is different because of their legislation on
      euthanasia. The use of the unclear terminology such as "passive euthanasia",
      "voluntary euthanasia" or "involuntary euthanasia" contributes to the confusion
      of lay people and physicians, and should therefore be avoided. End of life
      decisions in intensive care patients are in fact a structural part of work of
      intensivists. Collecting all necessary information including the wishes and will
      of the patient, medical expertise and acknowledging limitations of medical
      treatment will help to determine futility of treatment goals. Once it is
      determined that surviving the intensive care unit with a quality of life
      acceptable for the patient is beyond reach, the goal of treatment should be
      improved and the dying process optimized. Stopping a treatment modality at the
      request of a will-competent patient or because of futility is not euthanasia.

PMID- 21194802
TI  - [Boussignac CPAP in diagnostic-therapeutic procedures in the critical patient].
AB  - Boussignac valve is a new resource to consider in acute pulmonary edema
      cardiogenic management. As it generates positive airways pressure continuous
      (CPAP) and it is very simple to use, its use is being extended to emergency,
      urgency and hospitalization ward services. This valve is a small tube placed over
      the interface expiratory port. The gas flow (oxygen/air) accelerates when it
      crosses through four microchannels in the valve wall, pressurizing the bronchial
      tree by the principle of the energy in movement. It has a functioning, not
      hermetic system, allowing the passage of a catheter through it to help the
      patient (to drink, to eat, to aspirate, etc.). These characteristics make it
      possible to extend it use in those patients who, in extreme conditions, need
      diagnostic tests that could deteriorate their respiratory situation, such as
      endoscopy procedures. We report three critical patients who received CPAP with a
      Boussignac valve connected to an orofacial interface, while performing two
      fibrobronchoscopies and one upper digestive tract endoscopy. All finished
      successfully and none of them need orotracheal intubation.

PMID- 21194803
TI  - [Histological regression of liver fibrosis with immunosuppressive therapy in
      autoimmune hepatitis].
AB  - Reversibility of liver fibrosis with immunosuppressive therapy (IT) has been
      described in autoimmune hepatitis (AIH). OBJECTIVE: To compare initial fibrosis
      and fibrosis after IT in patients with AIH. METHODS: A total of 54 patients were
      admitted with positive ANA or AML antibodies, or both, elevated IgG
      immunoglobulins and who met international criteria for a diagnosis of AIH. The
      mean age was 39 years (range 13-65) and there were 47 women (87%). Two liver
      biopsies were taken: one at diagnosis and another at a mean of 28+/-8 months
      after initiation of IT with prednisone and azathioprine. The degree of
      inflammation (0-18) and fibrosis (0-6) according to Ishak score was compared
      between the initial and the follow-up biopsy. RESULTS: Fibrosis decreased from
      2.9+/-0.3 to 2.2+/-0.3 (p=0.005) and histological activity index from 6.8+/-0.45
      to 2.6+/-0.2 (P<.001). In subgroups, fibrosis decreased from 3.6+/-0.4 to 1.4+/
      0.3 (P<.001) in 22 patients (41%), was unchanged in 27 (50%) and increased in
      five (9%). There were seven patients with histological cirrhosis at IT
      initiation. After IT, four showed a reduction in Ishak score (achieving scores of
      0-3). Transaminase values were not associated with histological improvement.
      CONCLUSION: Fibrosis in patients with AIH significantly improved with IT,
      emphasizing the importance of studying the prognostic factors associated with
      this favorable response.

PMID- 21194804
TI  - [Polymorphism of mucA and fpvA genes in Pseudomonas aeruginosa isolates from
      cystic fibrosis patients: co-existence of genetically different variants].
AB  - INTRODUCTION: Pseudomonas aeruginosa is able to colonize the lungs of cystic
      fibrosis patients (CF) in an adaptive process that results in the selection of a
      dominant strain through a process of genetic variation. METHODS: One hundred and
      twenty tree isolates of P. aeruginosa were sequentially recovered from 6 CF
      patients during the routine follow-up or exacerbations over periods of 2 to 12
      years in the Ramon y Cajal University Hospital (Madrid, Spain). Another 13
      isolates were obtained from a single CF patient in a short-term study. They were
      analysed by restriction fragment length polymorphism (RFLP) and sequencing of
      mucA and fpvA genes, which code for the alginate biosynthesis regulator and a
      pyoverdin receptor, respectively, and their antibiotic susceptibility was studied
      by microdilution. RESULTS: A dominant colonising strain was found in each patient
      based on the RFLP profile. The polymorphisms of mucA and fpvA genes correlated
      well with these profiles, but suggested a relationship between strains isolated
      from two brothers, not inferred by RFLP. Stop codon mutations in mucA were unique
      to each dominant strain, indicating the adaptive process suffered. The alternate
      detection of the same mucA and/or fpvA genotypic variants suggested the
      coexistence of several subpopulations. This hypothesis was confirmed in a
      prospective study in which 6 variants were isolated in 7 days from the same
      patient. CONCLUSIONS: Genotypic variants of the P. aeruginosa dominant strains
      can coexist in the chronic colonization in CF patients. These variants can be
      undetected by RFLP and they might present variable antibiotic susceptibility.

PMID- 21194805
TI  - [Slowly enlarging erythematous macule].

PMID- 21194806
TI  - [Vertical transmission of methicillin resistant Staphylococcus aureus].

PMID- 21194807
TI  - [Results of a multidisciplinary and multifocal project to reduce bacteraemia
      caused by central venous catheters in non critical patients in a university
      hospital].
AB  - OBJECTIVE: To evaluate a multidisciplinary and multifocal intervention in order
      to reduce catheter related bloodstream infections (CRBI), based on previously
      identified risk factors in non-critical patients. METHODS: A pre-post
      intervention study, 2004-2006. POPULATION: patients with a central venous
      catheter (CVC). The primary endpoint was the CRBI. Other studied variables were
      patient characteristics, insertion, maintenance and removal of the catheter. The
      intervention consisted of baseline knowledge and identifying risk factors. In a
      second period, there was specific training on these identified risk factors and
      communication of the results, monitoring and evaluation of the CVC inserted.
      RESULTS: We analysed 175 and 200 CVC, respectively. The incidence of CRBI was
      15.4% during the pre-intervention and 4.0% in the post-intervention period
      (P<.001). The incidence of BRC by CVC days in the first group was 8.8 infections
      1.000 days of CVC and the second 2,3 (P=.0009). The multivariate analysis found
      an increased risk of CRBI during the first period (OR 4.32; 95% CI: 1.81-10.29)
      and the use of total parenteral nutrition (OR: 2.37; 95% CI: 1.10-5. 12).
      CONCLUSION: The application of specific measures directed at all non-critical
      patients in the entire hospital and involving a large number of professionals has
      achieved a decrease incidence of 73.9% of CRBI. An acceptable incidence of CRBI
      was obtained, and, with the completion of the project together with a new
      awareness, the situation will continue to improve.

PMID- 21194809
TI  - Synthesis and biological evaluation of 3,5-diaryl isoxazoline/isoxazole linked
      2,3-dihydroquinazolinone hybrids as anticancer agents.
AB  - A series of new 3,5-diaryl isoxazoline/isoxazole linked 2,3-dihydro quinazolinone
      hybrids with different linker architectures have been designed and synthesized.
      These compounds have been evaluated for their anticancer activity. One of the
      compounds 4c amongst this series has shown promising anticancer activity. Further
      some detailed biological assays relating to the cell cycle aspects and tubulin
      depolymerization activity have been examined with a view to understand the
      mechanism of action of this conjugate.

PMID- 21194808
TI  - Control measures for Acinetobacter baumannii: a survey of Spanish hospitals.
AB  - INTRODUCTION: Control of Acinetobacter baumannii is a challenge. METHODS: A
      survey was conducted on the control measures introduced against A baumannii in 30
      Spanish hospitals. RESULTS: We found significant differences in the application
      of contact precautions, active surveillance, hygiene of colonised patients,
      environmental cleaning, and educational activities. Hospitals with a written
      control program for A. baumannii had a lower incidence of colonisation/infection
      due to this organism. CONCLUSION: A multidisciplinary consensus document for the
      control of A. baumannii is needed in Spain.

PMID- 21194810
TI  - 3-benzylamino-beta-carboline derivatives induce apoptosis through G2/M arrest in
      human carcinoma cells HeLa S-3.
AB  - beta-carboline derivatives are known as the lead compounds for anti-tumor agents.
      To examine an optimal structure for anti-tumor activity, we synthesized a variety
      of beta-carboline derivatives, possessing a variety of substituents on the
      nitrogen atom of the amino group of 3-amino-beta-carboline, and evaluated their
      anti-tumor activity for HeLa S-3 cell line. 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay showed that an optimal structure for anti
      tumor activity was 3-cyclohexylmethylamino (1e) or 3-benzylamino-beta-carboline
      (1f). An optimal counter anion of 2-methyl-3-benzylamino- beta-carbolinium salts
      was a triflate anion 2c. In addition, the introduction of a hydroxyl group on the
      meta-position of the benzyl group of 3-benzylamino-beta-carboline (3e) enhanced
      its anti-tumor activity. Hoechst 33342 staining and DNA fragmentation assay
      suggested that 1f, 2c and 3e induced cell death by apoptosis unlike 1e. Flow
      cytometry analysis showed that 1f, 2c and 3e induced cell apoptosis through
      arrest of the cell cycle in the G2/M phase.

PMID- 21194811
TI  - Synthesis, antidepressant and antifungal evaluation of novel 2-chloro-8
      methylquinoline amine derivatives.
AB  - A new series of N-[(2-chloro-8-methylquinolin-3-yl)methyl]-(substituted)
      aniline/butylamine/cyclohexylamine/benzylamine derivatives (4a-p) was synthesized
      by nucleophilic substitution reaction of 2-chloro-3-(chloromethyl)-8
      methylquinoline 3 with various aliphatic and aromatic amines in absolute ethanol
      in the presence of triethylamine (TEA). The newly synthesized secondary amines
      were characterized by the combined use of IR, 1H NMR, 13C NMR, mass spectral data
      and microanalyses. The antidepressant activity of the synthesized compounds (4a
      p) was evaluated by Forced swim test in rats and their neurotoxicity was
      evaluated by the rotarod test. Test compounds and clomipramine were administered
      intraperitoneally at dose of 100 mg/kg and 20 mg/kg respectively. Preliminary
      antidepressant screening of compounds (4a-p) revealed that compounds 4b, 4c, 4d,
      4e, 4i and 4o significantly (P<0.01) reduces the duration of immobility time.
      These compounds were also tested in-vitro for MAO inhibitory effect. All the
      compounds were also screened for antifungal activity against Aspergillus niger
      MTCC 281, Aspergillus flavus MTCC 277, Monascus purpureus MTCC 369 and
      Penicillium citrinum NCIM 768 strains.

PMID- 21194812
TI  - 4-anilinoquinoline triazines: a novel class of hybrid antimalarial agents.
AB  - A novel class of hybrid 4-anilinoquinoline triazines have been synthesized and
      evaluated in vitro for their antimalarial activity against CQ-sensitive 3D7
      strain of P. falciparum as well as for their cytotoxicity toward VERO cell line.
      Five compounds (19, 20, 23, 41 and 45) exhibited the antimalarial potency
      superior to CQ. Compounds 14 and 16 were found to be orally active at a dose of
      100 mg/kg*4 days against CQ-resistant strain of P. yoelii. Inhibition of beta
      hematin formation assay and molecular docking study has been conducted in order
      to gain insight into the mechanism of action of proposed targets for the 4
      anilinoquinoline and triazine moiety of the hybrid compounds.

PMID- 21194813
TI  - Detection of tritium sorption on four soil materials.
AB  - In order to measure groundwater age and design nuclear waste disposal sites, it
      is important to understand the sorption behavior of tritium on soils. In this
      study, batch tests were carried out using four soils from China: silty clays from
      An County and Jiangyou County in Sichuan Province, both of which could be
      considered candidate sites for Very Low Level Waste disposal; silty sand from
      Beijing; and loess from Yuci County in Shanxi Province, a typical Chinese loess
      region. The experimental results indicated that in these soil media, the
      distribution coefficient of tritium is slightly influenced by adsorption time,
      water/solid ratio, initial tritium specific activity, pH, and the content of
      humic and fulvic acids. The average distribution coefficient from all of these
      influencing factors was about 0.1-0.2 mL/g for the four types of soil samples.
      This relatively modest sorption of tritium in soils needs to be considered in
      fate and transport studies of tritium in the environment.

PMID- 21194814
TI  - Computed tomography-guided implant surgery for dental rehabilitation in mandible
      reconstructed with a fibular free flap: description of the technique.
AB  - The fibular free flap, with or without a cutaneous component, is the gold
      standard for reconstructing mandibular defects. Dental prosthetic rehabilitation
      is possible this way, even if the prosthesis-based implant is still a challenge
      because of the many anatomical and prosthetic problems. We think that
      complications can be overcome or reduced by adopting the new methods of computed
      tomography (CT)-assisted implant surgery (NobelGuide, Nobel Biocare AB, Goteborg,
      Sweden). Here we describe the possibility of using CT-guided implant surgery with
      a flapless approach and immediate loading in mandibles reconstructed with fibular
      free flaps.

PMID- 21194815
TI  - Validation of a new method for building a three-dimensional physical model of the
      skull and dentition.
AB  - We present a new method for replicating the skull and occlusal surface with an
      accurate physical model that could be used for planning orthognathic surgery. The
      investigation was made on 6 human skulls, and a polyvinyl splint was fabricated
      on the dental cast of the maxillary dentition in each case. A cone beam computed
      tomogram (CBCT) was taken of each skull and a three-dimensional replica produced.
      The distorted dentition (as a result of magnification errors and streak
      artefacts) was removed from the three-dimensional model and replaced by new
      plaster dentition that was fabricated using the polyvinyl splint and a transfer
      jig replication technique. To verify the accuracy of the method the human skulls
      and the three dimensional replica model, with the new plaster dentition in situ,
      were scanned using a laser scanner. The three-dimensional images produced were
      superimposed to identify the errors associated with the replacement of the
      distorted occlusal surface with the new plaster dentition. The overall mean error
      was 0.72 and SD was (0.26)mm. The accuracy of the method encouraged us to use it
      clinically in a case of pronounced facial asymmetry.

PMID- 21194816
TI  - Preface to the IUFRO special section "Adaptation of forest ecosystems to air
      pollution and climate change".

PMID- 21194818
TI  - 'I'm a bad mum': pregnant presenteeism and poor health at work.
AB  - This paper contributes to research on women's health by challenging the 'common
      belief' that pregnant employees are prone to take sick leave. Conversely, it
      shows how some pregnant employees are so determined to appear 'well' that they
      remain at work when they are ill. The paper coins the phrase 'pregnant
      presenteeism' to describe pregnant employees who resist taking sick leave. The
      paper first acknowledges previous studies which show how employers associate
      pregnancy with incompetence and sickness absence. It then examines why (in
      contrast to employers' assumptions), some pregnant employees remain at work when
      they are ill. It does this through a qualitative study of 15 employed mothers in
      the UK, each of whom was working in a managerial/professional role at the time of
      her interview. Of these 15 women, three remained at work during pregnancy despite
      serious health problems. In order to understand the experiences of these
      'pregnant presentees', the paper draws upon Annandale and Clark's (1996) concept
      of a 'binary opposition' which articulates the tendency within medicine to
      polarize women's and men's health as if at opposite ends of a scale, with women's
      health classified as 'poor' and men's health as 'good'. The paper argues that the
      conceptual principles of 'binary opposition' spill over into workplace contexts
      especially in relation to pregnancy. It then proposes that some employed pregnant
      women deny their own ill health due to fear of being identified with the female,
      'poor health' end of the binary opposition scale. It articulates such denial as a
      potentially serious health issue for pregnant workers. The paper develops new and
      more explicit links between 'socio-cultural' feminist studies on the employed
      maternal body, and health research.

PMID- 21194817
TI  - Plasma exchange for renal vasculitis and idiopathic rapidly progressive
      glomerulonephritis: a meta-analysis.
AB  - BACKGROUND: Plasma exchange may be effective adjunctive treatment for renal
      vasculitis. We performed a systematic review and meta-analysis of randomized
      controlled trials of plasma exchange for renal vasculitis. STUDY DESIGN:
      Systematic review and meta-analysis of articles identified from electronic
      databases, bibliographies, and studies identified by experts. Data were
      abstracted in parallel by 2 reviewers. SETTING & POPULATION: Adults with
      idiopathic renal vasculitis or rapidly progressive glomerulonephritis. SELECTION
      CRITERIA FOR STUDIES: Randomized controlled trials that compared standard care
      with standard care plus adjuvant plasma exchange in adult patients with either
      renal vasculitis or idiopathic rapidly progressive glomerulonephritis.
      INTERVENTION: Adjuvant plasma exchange. OUTCOME: Composite of end-stage renal
      disease or death. RESULTS: We identified 9 trials including 387 patients. In a
      fixed-effects model, the pooled RR for end-stage renal disease or death was 0.80
      for patients treated with adjunctive plasma exchange compared with standard care
      alone (95% CI, 0.65-0.99; P = 0.04). No significant heterogeneity was detected (P
      = 0.5; I(2) = 0%). The effect of plasma exchange did not differ significantly
      across the range of baseline serum creatinine values (P = 0.7) or number of
      plasma exchange treatments (P = 0.8). The RR for end-stage renal disease was 0.64
      (95% CI, 0.47-0.88; P = 0.006), whereas the RR for death alone was 1.01 (95% CI,
      0.71-1.4; P = 0.9). LIMITATIONS: Although the primary result was statistically
      significant, there is insufficient statistical information to reliably determine
      whether plasma exchange decreases the composite of end-stage renal disease or
      death. CONCLUSIONS: Plasma exchange may decrease the composite end point of end
      stage renal disease or death in patients with renal vasculitis. Additional trials
      are required given the limited data available.

PMID- 21194820
TI  - Radial artery avulsion: a rare complication of percutaneous coronary
      intervention.

PMID- 21194819
TI  - Validation of the Spanish version of the Kansas city cardiomyopathy
      questionnaire.
AB  - INTRODUCTION AND OBJECTIVES: The Kansas City Cardiomyopathy Questionnaire (KCCQ)
      is specifically designed to evaluate quality of life in patients with chronic
      heart failure (CHF). The purpose of this study was to assess the reliability,
      validity, and responsiveness to change of the Spanish version of the KCCQ.
      METHODS: The multicenter study involved 315 patients with CHF. Patients were
      evaluated at baseline and at weeks 24 and 26. The KCCQ, the Minnesota Living with
      Heart Failure Questionnaire (MLHFQ), and the Short Form-36 (SF-36) were
      administered. Reliability was assessed in stable patients (n=163) by examining
      test-retest and internal consistency measures between weeks 24 and 26. Validity
      was evaluated at baseline (n=315) by determining how KCCQ scores varied with New
      York Heart Association functional class and by comparing scores with those on
      similar domains of the MLHFQ and SF-36. Responsiveness to change was assessed in
      patients who experienced significant clinical improvement between baseline and
      week 24 (n=31) by determining the effect size. RESULTS: Reliability coefficients
      ranged between 0.70 and 0.96 for the different domains. Mean KCCQ scores varied
      significantly with New York Heart Association functional class (P<.001).
      Correlations with comparable domains on the other questionnaires were acceptable
      (e.g. for physical limitation, they were between 0.77 and 0.81). The changes
      observed at 24 weeks in the majority of KCCQ scores in the subsample that
      improved corresponded to a moderate effect size (i.e. 0.4-0.6). CONCLUSIONS: The
      Spanish version of the KCCQ has good metric properties (i.e. validity,
      reliability and responsiveness), which make it suitable for use in evaluating
      quality of life in Spanish CHF patients.

PMID- 21194821
TI  - Value of molecular diagnosis in a family with Marfan syndrome and an atypical
      vascular phenotype.
AB  - Marfan syndrome is mainly caused by mutations in the FBN1 gene. Diagnosis is
      usually based on clinical criteria, but the phenotypic presentation varies widely
      among affected individuals. Aortic dissection or rupture is the cause of death in
      over 90% of untreated patients. Early identification of individuals at risk is
      important given the availability of medical and surgical treatment that can
      significantly improve life-expectancy. Molecular testing could provide an
      etiologic diagnosis in patients who present with milder or atypical clinical
      forms of the disease. Moreover, it could contribute to preventive treatment in
      carriers, inform genetic counseling and offer reassurance to unaffected
      individuals. By describing a family with Marfan syndrome in whom the disease
      presented in an atypical aggressive form, this article highlights the value of
      tests for detecting FBN1 mutations in selected cases.

PMID- 21194822
TI  - Acute heart failure in an adult patient with 2:1 atrial flutter: zebras or
      horses?

PMID- 21194824
TI  - Trends in leisure time and occupational physical activity in the Madrid region,
      1995-2008.
AB  - INTRODUCTION AND OBJECTIVES: Information on trends in physical activity is very
      scarce in Mediterranean countries, which have the highest sedentariness in
      Europe. This study describes recent trends in leisure time physical activity
      (LTPA) and at work in the Madrid region. METHODS: The data were taken from
      representative annual surveys of population aged 18-64 years, between 1995-2008,
      28,084 people participated. We calculated total energy, quantified in metabolic
      equivalent (MET-1 h per week), spent on LTPA and on light LTPA (<3 MET), moderate
      LTPA (3-6 MET) and vigorous LTPA (>6 MET). The annual change in LTPA was
      estimated by linear regression, and occupational activity by logistic regression,
      adjusting for age, gender and educational level. RESULTS: The total amount of
      LTPA in MET-1 h per week declined by 19.8% (P<.001) between 1995-2008; for both
      genders, all age groups and educational levels, except for those with the lowest
      level of education. The adjusted annual change in MET-1 h per week was: -0.21
      (P<.001) for total LTPA; -0.1 (P<.001) for light; -0.08 (P<.001) for moderate;
      and -0.03 (P=.192) for vigorous. This decline is reflected by a shift to the left
      of the LTPA distribution in the population. Occupational physical inactivity has
      increased in the general population (odds ratio for annual change=1.01; 95%
      confidence interval, 1-1.02); specially in women, young and middle aged, and
      intermediate educational level. CONCLUSIONS: There has been a decline in LTPA,
      mainly in light and moderate activities, accompanied by greater occupational
      physical inactivity. This could have contributed to the increase in obesity in
      the Community of Madrid between 1995-2008.

PMID- 21194825
TI  - Traumatic dissection of a coronary artery: detection by multislice computed
      tomography and use of tirofiban as a reversible platelet inhibitor.
AB  - We report on a trauma victim without history of or risk factors for cardiac
      disease, who suffered coronary artery dissection caused by blunt chest injury
      (BCI). Myocardial ischaemia was detected by multislice computed tomography (MSCT)
      promptly after trauma centre admission and managed by immediate
      revascularisation. Thoracic trauma may cause myocardial ischaemia in the absence
      of a specific risk profile. MSCT, as part of initial work-up in severely injured
      patients, may support differential diagnosis after BCI. Tirofiban and
      unfractionated heparin as short-acting anticoagulants warrant stent patency and
      concurrently offer the possibility of quick recovery of haemostasis in case of
      haemorrhage.

PMID- 21194826
TI  - Ovarian tumours in pregnancy: a literature review.
AB  - Ovarian tumours in pregnancy are a diagnostic and management challenge that is
      increasingly being faced by the clinician. While most masses are benign and
      resolve spontaneously, there are others that persist and indicate the need for
      surgical management. Ultrasound not only detects asymptomatic masses but also
      helps to guide their management based on presence or absence of features
      suspicious of malignancy. The role of tumour markers in pregnancy is limited due
      to their non-specific nature. Most masses treated in pregnancy are benign (most
      commonly dermoids), and most malignancies are either of low malignant potential
      or germ cell tumours, usually early stage disease. Surgical management is
      indicated for symptomatic masses or those with increasing size or complexity
      indicating possible malignancy. Both laparoscopy and laparotomy have similar
      results with regard to obstetric outcome. Conservative management is preferred in
      the remainder. MRI may help in better characterization of doubtful masses.
      National tumour registries can help to establish guidelines.

PMID- 21194823
TI  - Randomized clinical trial to assess the efficacy of a comprehensive programme of
      secondary prevention of cardiovascular disease in general practice: the PREseAP
      study.
AB  - INTRODUCTION AND OBJECTIVES: To assess the efficacy of a comprehensive program of
      secondary prevention of cardiovascular disease in general practice. METHODS: A
      cluster randomized clinical trial was carried out in a regular general practice
      setting. Male and female patients aged under 86 years with a diagnosis of
      ischemic heart disease, stroke or peripheral artery disease were recruited
      between January 2004 and May 2005. Study participants were seen at 42 health
      centers throughout the whole of Spain. The primary endpoint was the combination
      of all-cause mortality and hospital cardiovascular readmission at 3-year follow
      up. RESULTS: In total, 1224 patients were recruited: 624 in the intervention
      group and 600 in the control group. The primary endpoint was observed in 29.9%
      (95% confidence interval [CI], 25.5-34.8%) in the intervention group and 25.6%
      (22.3-29.2%) in the control group (P=.15). At the end of follow-up, 8.5% (6.3
      11.3%) in the intervention group and 11% (7.4-16%) in the control group were
      smokers (P=.07). The mean waist circumference of patients in the intervention and
      control groups was 100.44 cm (95% CI, 98.97-101.91 cm) and 102.58 cm (95% CI,
      100.96-104.21 cm), respectively (P=.07). Overall, 20.9% (15.6-27.7%) of patients
      in the intervention group and 29.6% (23.9-36.1%) in the control group suffered
      from anxiety (P=.05), and 29.6% (22.4-37.9%) in the intervention group and 41.4%
      (35.8-47.3%) in the control group had depression (P=.02). CONCLUSIONS: A
      comprehensive program of secondary prevention of cardiovascular disease in
      general practice was not effective in reducing cardiovascular morbidity and
      mortality. However, some factors associated with a healthy lifestyle were
      improved and anxiety and depression were reduced.

PMID- 21194827
TI  - Efficacy of mefenamic acid and hyoscine for pain relief during saline infusion
      sonohysterography in infertile women: a double blind randomized controlled trial.
AB  - OBJECTIVES: To evaluate the efficacy and level of satisfaction from mefenamic
      acid and hyoscine when used for pain relief during saline infusion
      sonohysterography. STUDY DESIGN: In this double blind randomized controlled
      trial, 141 nulliparous women were allocated to receive 500 mg of mefenamic acid,
      10mg of hyoscine or a placebo, which was packed in the same outer capsule. Saline
      infusion sonohysterography (SIS) was performed 30 min later by one operator. Pain
      and satisfaction scores were evaluated using a 10 cm visual analog scale.
      Baseline characteristics, pain and satisfaction scores were compared among the
      three groups. Pain scores were recorded before, after catheter insertion, during,
      immediately after, and 30 min after the procedure. RESULTS: No statistically
      significant differences were found in baseline characteristics, pain and
      satisfaction scores among the three groups. Maximum pain during SIS was 4.40 +/-
      3.34, 4.67 +/- 3.14 and 4.85 +/- 3.19 in the mefenamic acid, hyoscine and placebo
      groups respectively. There was a 31.1% prevalence of intrauterine abnormality and
      the most frequent finding was endometrial polyp. CONCLUSION: There is no benefit
      in using mefenamic acid and hyoscine in the prevention of pain occurring from
      SIS.

PMID- 21194828
TI  - The epidemiology of Candida species associated with vulvovaginal candidiasis in
      an Iranian patient population.
AB  - OBJECTIVES: Vulvovaginal candidiasis is a common infection among women worldwide.
      According to previous epidemiological studies, Candida albicans is the most
      common species of Candida. The prevalence of non-Candida species, however, is
      increasing. Identification of Candida species among the population will not only
      help health professionals to choose suitable antifungal treatments, but also
      prevent development of drug resistance. The aim of this study was to identify,
      using chromogenic agar medium, the Candida species associated with vulvovaginal
      candidiasis among a sample of the Iranian population. STUDY DESIGN: In a
      prospective cohort study during a two year period from March 2006 to March 2008,
      swab samples of vaginal discharge/secretion were taken from 200 patients admitted
      to the gynecology clinic of Mahdieh Hospital (Tehran, Iran) with a clinical
      presentation suggestive of vulvovaginal candidiasis. The isolates obtained were
      cultured on Sabouraud dextrose agar and chromogenic agar medium. Candida species
      were also identified by germ tube formation in serum, chlamydospore production on
      Corn Meal Agar and carbohydrate absorption using the API 20C-AUX kit.
      Participants were asked to complete a questionnaire investigating the risk
      factors associated with candidiasis. An assessment of the different species of
      recurrent and non-recurrent candidiasis was also made. Descriptive statistics,
      chi-square test, and t-test were used to analyze the data. RESULTS: A total of
      191 isolates were obtained from 175 vaginal specimens. Candida albicans accounted
      for 67% of the strains including single and mixed infections. The other
      identified species were Candida glabrata (18.3%), Candida tropicalis (6.8%),
      Candida krusei (5.8%), Candida parapsilosis (1.6%), and Candida guilliermondii
      (0.5%) respectively. Mixed infection with two or more species of Candida was seen
      in 10.3% of patients. The most common mixed cause was the combination of Candida
      albicans and Candida glabrata. Participants who were sexually active and those
      who had orogenital sex were more likely to suffer recurrent vulvovaginal
      candidiasis. CONCLUSIONS: Candida albicans was the most common cause of recurrent
      and non-recurrent vulvovaginitis. The second most common species was Candida
      glabrata. This study suggests CHROMagar method as a convenient and cost effective
      yet reliable method to isolate the species of Candida especially in cases where
      more than one species is present.

PMID- 21194829
TI  - Solid waste management in European countries: a review of systems analysis
      techniques.
AB  - In the past few decades, solid waste management systems in Europe have involved
      complex and multi-faceted trade-offs among a plethora of technological
      alternatives, economic instruments, and regulatory frameworks. These changes
      resulted in various environmental, economic, social, and regulatory impacts in
      waste management practices which not only complicate regional policy analysis,
      but also reshape the paradigm of global sustainable development. Systems
      analysis, a discipline that harmonizes these integrated solid waste management
      strategies, has been uniquely providing interdisciplinary support for decision
      making in this area. Systems engineering models and system assessment tools, both
      of which enrich the analytical framework of waste management, were designed
      specifically to handle particular types of problems. Though how to smooth out the
      barriers toward achieving appropriate systems synthesis and integration of these
      models and tools to aid in the solid waste management schemes prevalent in
      European countries still remains somewhat uncertain. This paper conducts a
      thorough literature review of models and tools illuminating possible overlapped
      boundaries in waste management practices in European countries and encompassing
      the pros and cons of waste management practices in each member state of the
      European Union. Whereas the Southern European Union (EU) countries need to
      develop further measures to implement more integrated solid waste management and
      reach EU directives, the Central EU countries need models and tools with which to
      rationalize their technological choices and management strategies. Nevertheless,
      considering systems analysis models and tools in a synergistic way would
      certainly provide opportunities to develop better solid waste management
      strategies leading to conformity with current standards and foster future
      perspectives for both the waste management industry and government agencies in
      European Union.

PMID- 21194830
TI  - Chemical absorption of carbon dioxide with asymmetrically heated
      polytetrafluoroethylene membranes.
AB  - In this study, the absorption of carbon dioxide using an absorbent composed of 2
      amino-2-methyl-L-propanol (AMP) + monoethanolamine (MEA) + piperazine (PZ) in
      asymmetric and symmetric polytetrafluoroethylene (PTFE) membrane contactors was
      investigated. Experiments were conducted using various gas flow rates, liquid
      flow rates, and absorbent blends. CO(2) recovery increased with increasing liquid
      flow rates. The mean pore size of PTFE membrane reduced via heating treatment. An
      asymmetric membrane had a better CO(2) recovery than a symmetric membrane. For
      the asymmetric membrane, placing the smaller pore-size side of the membrane in
      contact with the liquid phase, reduced the level of wetting of the membrane. The
      membrane mass transfer coefficient and durability of the PTFE membrane were
      enhanced by asymmetrically heating.

PMID- 21194831
TI  - A prognostic model for patients with metastatic renal cell cancer: what's new?

PMID- 21194833
TI  - Enzyme prodrug therapy designed to target L-methioninase to the tumor
      vasculature.
AB  - A new approach for enzyme prodrug therapy for cancer was tested using human
      endothelial cells and two breast cancer cell lines in vitro. The concept is to
      use the human annexin V protein to selectively target the enzyme L-methioninase
      to the tumor vasculature. The major finding was that enzyme prodrug treatment
      using the L-methioninase-annexin V fusion protein and selenomethionine as the
      prodrug over 3 days was shown to be lethal to the endothelial cells and the
      cancer cells, while having little or no effect with the prodrug but with no
      fusion protein present. Thus, this new approach appears promising.

PMID- 21194834
TI  - Analysis of coal tar pitch and smoke extract components and their cytotoxicity on
      human bronchial epithelial cells.
AB  - Coal tar pitch and its smoke are considered hazardous by-products and common
      pollutant generated from coal industry processing. In this study, coal tar pitch
      and its smoke extracts were characterized by gas chromatography/mass spectrometry
      (GC/MS) with dimethylsulfoxide. We identified only 0.3025% of components in the
      total coal tar pitch using GC/MS. Among 18 identified compounds, polycyclic
      aromatic hydrocarbons (PAHs) has the highest relative abundance (0.19%). The
      remaining components were composed of monocyclic aromatic hydrocarbons,
      heterocyclic compounds and alkenes. In contrast, among 38 coal tar pitch smoke
      extract constituents that have been profiled, 87.91% were PAHs, and the remaining
      12.09% were composed of monocyclic aromatic hydrocarbons, heterocyclic compounds
      and alkenes. The cytotoxic effect of coal tar pitch and its smoke extracts on
      BEAS-2B cells were also evaluated by MTT assay. BEAS-2B cells exposed to coal tar
      pitch showed a non dose-dependent U-shaped cytotoxicity with a dosage for maximal
      inhibitory of 3.75 mg/L. In contrast, BEAS-2B cells exposed to coal tar pitch
      smoke extracts showed a dose dependent cytotoxicity with a LC(50) of 8.64 mg/L.
      Our study demonstrated the significant different composition and cytotoxicity of
      coal tar pitch and its extracts, suggesting two different underlying mechanisms
      that are pending future investigation.

PMID- 21194832
TI  - Ginsenoside Rh2 induces apoptosis and paraptosis-like cell death in colorectal
      cancer cells through activation of p53.
AB  - Ginsenosides are the main bioactive components in American ginseng, a commonly
      used herb. In this study, we showed that the ginsenoside Rh2 exhibited
      significantly more potent cell death activity than the ginsenoside Rg3 in HCT116
      and SW480 colorectal cancer cells. Cell death induced by Rh2 is mediated in part
      by the caspase-dependent apoptosis and in part by the caspase-independent
      paraptosis, a type of cell death that is characterized by the accumulation of
      cytoplasmic vacuoles. Treatment of cells with Rh2 activated the p53 pathway and
      significantly increased the levels of the pro-apoptotic regulator, Bax, while
      decreasing the levels of anti-apoptosis regulator Bcl-2. Removal of p53
      significantly blocked Rh2-induced cell death as well as vacuole formation,
      suggesting that both types of cell death induced by Rh2 are mediated by p53
      activity. Furthermore, we show that Rh2 increased ROS levels and activated the NF
      kappaB survival pathway. Blockage of ROS by NAC or catalase inhibited the
      activation of NF-kappaB signaling and enhanced Rh2-induced cell death, suggesting
      that the anti-cancer effect of Rh2 can be enhanced by antioxidants.

PMID- 21194835
TI  - A sustainable route for the preparation of activated carbon and silica from rice
      husk ash.
AB  - An environmentally friendly and economically effective process to produce silica
      and activated carbon form rice husk ask simultaneously has been developed in this
      study. An extraction yield of silica of 72-98% was obtained and the particle size
      was 40-50 nm. The microstructures of the as-obtained silica powders were
      characterized by X-ray diffraction (XRD) and infrared spectra (IR). The surface
      area, iodine number and capacitance value of activated carbon could achieve 570
      m(2)/g, 1708 mg/g, 180 F/g, respectively. In the whole synthetic procedure, the
      wastewater and the carbon dioxide were collected and reutilized. The recovery
      rate of sodium carbonate was achieved 92.25%. The process is inexpensive,
      sustainable, environmentally friendly and suitable for large-scale production.

PMID- 21194836
TI  - Retention of phenylarsenicals in soils derived from volcanic materials.
AB  - Sorption of phenylarsenicals including 4-hydroxy-3-nitrophenylarsonic acid
      (roxarsone), an animal feed additive widely used for growth stimulation, on soils
      was investigated in batch systems. Phenylarsonic acid, o-arsanilic acid and
      roxarsone were retained differently by unpolluted, non-sterilized soils. Sorption
      isotherms were analyzed by the Henry, Toth and Langmuir-Freundlich equations. The
      saturation capacity of the Acrisol soil was 3.4 for o-arsanilic acid, 10.9 for
      phenylarsonic acid and 1.9 g(As) kg(soil)(-1) (dry mass) for roxarsone. The iron
      content in the soil was not the only factor determining retention of the studied
      phenylarsenicals. The order of retention on the three soils after 24 h was:
      roxarsone>o-arsanilic acid>phenylarsonic acid. Besides arsenite and arsenate, new
      arsenic-containing compounds were detected.

PMID- 21194837
TI  - Dual substrates biodegradation kinetics of m-cresol and pyridine by
      Lysinibacillus cresolivorans.
AB  - Phenols and N-heterocyclic compounds are found to co-exist in actual wastewater,
      especially in petrochemical and coking wastewater. Lysinibacillus cresolivorans,
      a bacterium capable of phenol-biodegradation was used to study the substrate
      interactions of m-cresol and pyridine as single and dual substrates. The cell
      growth and substrate biodegradation kinetics were also investigated with initial
      m-cresol concentrations varying from 0 to 1200 mg/L and pyridine concentrations
      varying from 0 to 150 mg/L. The single substrate kinetics was well described by
      the Haldane kinetic models. The single-substrate parameter values of m-cresol on
      cell growth were MU(max)=0.89 h(-1), K(s)=426.25 mg/L, K(i)=51.26 mg/L and
      MU(max)=0.0925 h(-1), K(s)=60.28 mg/L, K(i)=16.17 mg/L for cell growth on
      pyridine. Inhibitory effects of substrates were observed when cells were grown on
      the mixed substrates. The interaction parameter I(m,p) (0.76) was greater than
      I(m,p) (0.11), which indicated that m-cresol inhibited the utilization of
      pyridine much more than pyridine inhibited the biodegradation of m-cresol. The
      study showed a good potential of L. cresolivorans in degrading mixed substrates
      of m-cresol and pyridine.

PMID- 21194838
TI  - Association between long-term exposure to outdoor air pollution and mortality in
      China: a cohort study.
AB  - No prior cohort studies exist in China examining the association of outdoor air
      pollution with mortality. We studied 70,947 middle-aged men and women in the
      China National Hypertension Survey and its follow-up study. Baseline data were
      obtained in 1991 using a standard protocol. The follow-up evaluation was
      conducted in 1999 and 2000. Annual average air pollution exposure between 1991
      and 2000, including total suspended particle (TSP), sulfur dioxide (SO(2)) and
      nitrogen oxides (NO(x)), were estimated by linking fixed-site monitoring data
      with resident zip code. We examined the association of air pollution with
      mortality using proportional hazards regression model. We found significant
      associations between air pollution levels and mortality from cardiopulmonary
      diseases and from lung cancer. Each 10 MUg/m(3) elevation of TSP, SO(2) and NO(x)
      was associated with a 0.9% (95%CI: 0.3%, 1.5%), 3.2% (95%CI: 2.3%, 4.0%), and
      2.3% (95%CI: 0.6%, 4.1%) increased risk of cardiovascular mortality,
      respectively. We found significant effects of SO(2) on mortality after adjustment
      for TSP. Conclusively, ambient air pollution was associated with increased
      cardiopulmonary and lung cancer mortality in China. These data contribute to the
      scientific literature on long-term effects of air pollution for high exposure
      settings typical in developing countries.

PMID- 21194839
TI  - Are the effects of acupuncture specific or nonspecific?

PMID- 21194840
TI  - Morphological and biometrical features of Trypanosoma evansi isolates from an
      outbreak in mainland Spain.
AB  - According to several authors, Trypanosoma evansi is a monomorphic trypanosome
      found exclusively in slender intermediate forms, although additional studies have
      revealed that many strains present stumpy forms on rare occasions. In a recent T.
      evansi outbreak in mainland Spain, several atypical forms were observed in blood
      smear examinations. Molecular procedures were then necessary to confirm the
      causal agent. Morphological and biometric measures were taken to characterize the
      different forms of T. evansi. In contrast to published information, the results
      of this study would indicate that biometrically distinct T. evansi could also be
      found in the same farm and even in the same animal species. These data could be
      useful for many trypanosomes endemic areas of the world where molecular methods
      are not commonly available.

PMID- 21194842
TI  - Burns patients with epilepsy or a learning disability have a greater length of
      stay in hospital than those patients with a history of drug or alcohol abuse.

PMID- 21194841
TI  - Molecular detection of Babesia bovis and Babesia bigemina in white-tailed deer
      (Odocoileus virginianus) from Tom Green County in central Texas.
AB  - Serologic and molecular evidence suggest that white-tailed deer in South Texas
      and North Mexico carry the agents of bovine babesiosis, Babesia bovis and Babesia
      bigemina. To determine if white-tailed deer in central Texas, which is outside
      the known occurrence of the vector tick at this time, harbor these parasites,
      blood samples from free-ranging and captive white-tailed deer (Odocoileus
      virginianus) in Tom Green County were tested by polymerase chain reaction (PCR)
      assays for B. bovis and B. bigemina 18S rDNA. Of the 25 samples tested, three
      (12%) were positive by nested PCR for B. bovis. This identity was confirmed by
      sequence analysis of the cloned 18S rDNA PCR product. Further confirmation was
      made by sequence analysis of the rRNA internal transcribed spacer (ITS) 1, 5.8S
      rRNA gene, and ITS 2 genomic region in two (representing samples from two
      different ranches) of the B. bovis positive samples. Three samples were positive
      by B. bigemina nested PCR, but sequencing of the cloned products confirmed only
      one animal positive for B. bigemina; Theileria spp. DNA was amplified from the
      other two animal samples. In addition to Theileria spp., two genotypically unique
      Babesia species sequences were identified among the cloned sequences produced by
      the B. bigemina primers in one sample. Phylogenetic analysis showed no separation
      of the deer B. bovis or B. bigemina 18S rDNA, or deer B. bovis ITS region
      sequences from those of bovine origin. Clarification of the possible role of
      white-tailed deer as reservoir hosts in maintaining these important pathogens of
      cattle is critical to understanding whether or not deer contribute to the
      epidemiology of bovine babesiosis.

PMID- 21194843
TI  - Hemostasis in burn surgery--a review.
AB  - Over the past 30 years, techniques of early excision and grafting along with
      enhancement of critical care have significantly improved survival following burn
      injury. Despite these advancements, large volume blood loss associated with
      surgical intervention continues to be a challenging aspect of burn surgery. This
      review article will examine the methods of limiting blood loss during surgical
      procedures.

PMID- 21194844
TI  - Effects of single cortisol administrations on human affect reviewed: Coping with
      stress through adaptive regulation of automatic cognitive processing.
AB  - The human stress hormone cortisol may facilitate effective coping after
      psychological stress. In apparent agreement, administration of cortisol has been
      demonstrated to reduce fear in response to stressors. For anxious patients with
      phobias or posttraumatic stress disorder this has been ascribed to hypothetical
      inhibition of retrieval of traumatic memories. However, such stress-protective
      effects may also work via adaptive regulation of early cognitive processing of
      threatening information from the environment. This paper selectively reviews the
      available literature on effects of single cortisol administrations on affect and
      early cognitive processing of affectively significant information. The concluded
      working hypothesis is that immediate effects of high concentration of cortisol
      may facilitate stress-coping via inhibition of automatic processing of goal
      irrelevant threatening information and through increased automatic approach
      avoidance responses in early emotional processing. Limitations in the existing
      literature and suggestions for future directions are briefly discussed.

PMID- 21194845
TI  - Life events, cortisol and levels of prostate specific antigen: a story of
      synergism.
AB  - BACKGROUND: Previous studies have tested the relationship between stressful life
      events (LE) and cancer onset, but inconsistent results have been found. One
      possibility is that the LE-cancer relation may depend on other biological factors
      pertinent to stress and cancer. METHODS: This study examined the relationship
      between LE and prostate specific antigen (PSA) levels, a tumor marker, and
      whether cortisol mediates or moderates a LE-PSA relationship. During a voluntary
      screening for prostate cancer risk, 139 men (mean age=57.3 years) were assessed
      with the Holmes and Rahe questionnaire about their LE during the past 1-5 years,
      and their PSA and serum cortisol levels were measured. RESULTS: LE and cortisol
      alone were unrelated to PSA. However, statistically controlling for age, body
      mass index and the ratio of triglycerides to HDL cholesterol, we found evidence
      for a synergistic interaction between LE and cortisol. Among men with low
      cortisol, number of LE were inversely and significantly correlated with PSA (r=
      0.265, p<0.05), while in men with high cortisol, number of LE were positively and
      significantly correlated with PSA (r=0.344, p<0.01). These results more
      consistently stemmed from the effects of uncontrollable LE. Similar results were
      found, using a clinically significant PSA cut-off. CONCLUSIONS: These results
      suggest considering the joint effects of psychosocial and biological factors in
      relation to possible cancer risk, where the hypothalamic pituitary adrenal axis
      may moderate stress-cancer risk associations.

PMID- 21194846
TI  - Mangiferin: a possible strategy for periodontal disease to therapy.
AB  - Periodontitis is one of the most widespread infectious inflammatory diseases,
      characterized by chronic bacterial infection of the supporting structures of the
      teeth, leading to tooth loss in adults. Mangiferin, a naturally occurring
      glucosylxanthone, has recently gained great attention, owing to potent
      antioxidant, anti-inflammatory, antidiabetic, immunomodulatory, and antitumor
      properties. These studies confirm that mangiferin, exert excellent antioxidant
      effect and act rapidly in the face of oxidative stress. Meanwhile, mangiferin
      could significantly inhibit the expression of pro-inflammatory cytokines.
      Especially, treated with mangiferin, the alveolar bone loss of rats with
      experimental periodontitis has been remarkably reduced. Given these bioactivity
      exhibited for mangiferin, we hypothesized that mangiferin may play an efficient
      role in therapy of periodontitis, which may offer new therapeutic options for the
      management of patients with periodontitis.

PMID- 21194847
TI  - Low level laser can be a novel adjuvant method for orthodontic tooth movement on
      postmenopausal women.
AB  - Osteoporosis, a pathological state commonly saw on postmenopausal women, has
      shown to affect jaw bone and the periodontium. While more and more adult patients
      seeking orthodontic treatment for a beautiful smile, the current strategy has not
      work well for extraction space closure in postmenopausal women with osteoporosis
      and concurrent bisphosphates taken. A new and non-invasive method is hoped to
      make a beginning. There are ample evidences showing low level laser has favorable
      effects on pain relief and wound healing procedure of hard and soft tissue. These
      effects are due to its ability to stimulate cell metabolism, angiogenesis, bone
      formation and osteoclastogenesis. The hypothesis we proposed herein is that low
      level laser may be a valuable adjuvant method for protecting and facilitating
      orthodontic tooth movement on this kind of patients.

PMID- 21194848
TI  - Effect of serial arm ischemic preconditioning sessions on the systemic blood
      pressure of a normotensive subject.
AB  - Remote ischemic preconditioning (RIPC) consists of repeated 5' periods of blood
      pressure (BP) cuff inflations applied to the upper arms at pressures above the
      systolic blood pressure (SBP), interspersed with 5' periods of reperfusion have
      been shown to benefit the ischemic and infarcted myocardium in animal
      experiments, and human clinical experience. Serial sessions of RIPC, as
      described, were applied to the arms of a normotensive subject. RIPC resulted in a
      statistically significant mean drop of the SBP by >6mm Hg, of the diastolic BP by
      >3mm Hg, and of the pulse pressure by 3mm Hg, 30' after RIPC, with some evidence
      for a delayed effect in the ensuing days following RIPC. RIPC exerts an immediate
      BP lowering effect and possibly has a prolonged delayed such influence on BP.
      This newly described herein phenomenon needs to be corroborated and explored for
      its potential value in the physiology of BP regulation and the pathophysiology
      and therapy of hypertension.

PMID- 21194849
TI  - Effects of dietary antioxidants on the quality, fatty acid profile, and lipid
      oxidation of longissimus muscle in Kacang goat with aging time.
AB  - Thirty-two male goats were randomly assigned to four dietary treatments namely,
      basal diet 70% concentrate and 30% oil palm fronds (control, CN), CN + 400 mg/kg
      vitamin E (VE), 0.5% turmeric (TU) or 0.5% Anderographis paniculata (AP). After
      100 days of feeding, the goats were slaughtered and longissimus dorsi (LD) muscle
      was sampled. The muscle was vacuum-packaged and conditioned for 0, 7 and 14 days
      in a chiller (4  degrees C). The drip loss of the LD muscle increased (P < 0.05)
      with aging time. Meat tenderness was improved (p < 0.05) at 14 days aging. All
      antioxidant supplements improved (P < 0.05) colour of the meat. The TBARS value
      increased (P < 0.05) at 7 days of aging while the fatty acid composition was not
      affected by the dietary supplements. It is concluded that TU and AP are potential
      dietary antioxidant supplements, for the purpose of improving the quality of
      chevon.

PMID- 21194850
TI  - Effects of moisture enhancement, enzyme treatment, and blade tenderization on the
      processing characteristics and tenderness of beef semimembranosus steaks.
AB  - The individual and combined effects of moisture enhancement with a salt/phosphate
      solution (ME), blade tenderization (BT), and enzyme injection with proteinases
      derived from Aspergillus oryzae or Bacillus subtilis on cooking properties,
      Warner-Bratzler shear force (WBSF), and sensory characteristics of beef
      semimembranosus were investigated. ME significantly (P < 0.01) reduced WBSF and
      increased (P < 0.05) sensory scores for juiciness and tenderness. BT increased (P
      < 0.05) initial and overall tenderness scores and made connective tissue less
      perceptible. BT combined with ME resulted in the highest initial and overall
      tenderness scores, however, combining ME with either proteinase was as effective
      for reducing WBSF and increasing tenderness, particularly at 20 (vs. 10) ppm
      enzyme inclusion. Tenderness of enzyme-injected steaks was increased without
      compromising other palatability attributes. All treatments increased the
      frequency of steaks rated slightly tender or higher, with the ME+BT combination,
      or ME with inclusion of 20 ppm of either proteinase, being most effective.

PMID- 21194851
TI  - High podoplanin expression in cancer cells predicts lower incidence of nodal
      metastasis in patients with lung squamous cell carcinoma.
AB  - Podoplanin is expressed in a variety of malignant cells, and is generally
      regarded as a factor promoting tumor progression in conventional studies.
      Conversely, a recent clinicopathological study has revealed that low podoplanin
      in cancer cells was correlated with poor prognosis of patients with stage IB lung
      squamous cell carcinoma (LSCC). We here evaluated the clinicopathological
      relationship between cancer-cell podoplanin expression and clinicopathological
      parameters in 40 cases of LSCC (stage I-III). Immunohistochemical podoplanin
      expression significantly correlated with N classification and pathological stage,
      but not with other clinicopathological parameters. Notably, all 16 cases with
      high podoplanin expression unexceptionally exhibited pathological N0 status.
      Cases without nodal metastasis showed a significantly higher podoplanin-positive
      score. Furthermore, patients with high podoplanin expression exhibited a
      significantly longer survival time and disease-free time. These findings suggest
      that immunohistochemical analysis for podoplanin may serve as a marker of risk of
      nodal metastasis and prognosis in patients with LSCC.

PMID- 21194852
TI  - Factors associated with hepatitis C knowledge among a sample of treatment naive
      people who inject drugs.
AB  - BACKGROUND: Assessment and uptake of treatment for hepatitis C among people who
      inject drugs (PWID) is low and strategies to enhance hepatitis C care in this
      group are needed. Knowledge of hepatitis C and its treatment is one precursor to
      decisions about treatment. METHODS: We conducted a cross-section study designed
      to evaluate treatment considerations in participants with self-reported hepatitis
      C infection in New South Wales, Australia. Participants were recruited from
      needle and syringe programs, opiate substitution clinics, pharmacies that
      dispensed opiate substitution treatment and from the mailing list of a community
      based hepatitis C organisation and completed a self-administered survey.
      Knowledge of hepatitis C was assessed by a 48-item scale addressing the natural
      history and treatment of hepatitis C. Factors associated with knowledge were
      assessed by ordinal regression. RESULTS: Among the 997 participants recruited,
      407 self-reported acquiring hepatitis C through injecting drug use and had never
      received hepatitis C treatment. Knowledge about hepatitis C was overall poor and
      the effects of the long term consequences of hepatitis C were over-estimated.
      Higher knowledge scores were associated with recruitment site, higher education
      levels and recent contact with a general practitioner. One-third of participants
      indicated that they did not intend to have treatment and one-fifth did not answer
      this question. CONCLUSION: Knowledge is a precursor to informed decisions about
      hepatitis C treatment. These results indicate that efforts to support those less
      engaged with hepatitis C care (and specifically those on opiate substitution
      treatment) and those with lower literacy are required.

PMID- 21194853
TI  - Smoking outcome expectancies in young adult female smokers: individual
      differences and associations with nicotine dependence in a genetically
      informative sample.
AB  - Outcome expectancy is a central construct in models of addiction. Several outcome
      expectancies associated with smoking cigarettes have been identified, and studies
      suggest that individual differences in smoking expectancies are related to
      important aspects of tobacco use, including levels of smoking, nicotine
      dependence and smoking cessation. In the present study, we used a novel analytic
      method, exploratory structural equation modeling (ESEM), to quantify smoking
      expectancies from a subset of items adapted from the Smoking Consequences
      Questionnaire (SCQ; Brandon and Baker, 1991) and SCQ-Adult (Copeland et al.,
      1995). In our sample of 1262 monozygotic and dizygotic young adult, female twins
      who were regular smokers, we quantified six smoking expectancy factors similar to
      those reported in previous studies. These included Negative Affect Reduction,
      Boredom Reduction, Weight Control, Taste Manipulation, Craving/Addiction and
      Stimulation-state Enhancement. We used genetic model-fitting to examine the
      extent to which individual differences in the expectancies were influenced by
      latent genetic, shared environmental and non-shared environmental factors. We
      also examined the validity of the expectancy factors by examining their
      associations with nicotine dependence (ND) before and after adjusting for
      comorbid diagnoses of drug dependence and alcohol use disorder. Results of the
      validity analysis indicated that all of the expectancies were associated with ND
      after covariate adjustment. Although we lacked the statistical power to
      distinguish between genetic and shared environmental sources of variance, our
      results suggest that smoking outcome expectancies aggregate in families, but the
      majority of variance in these expectancies is due to environmental factors
      specific to the individual.

PMID- 21194854
TI  - Prenatal stress and infant affective reactivity at five months of age.
AB  - BACKGROUND: prospective studies concerning prenatal stress and its outcome on
      children's emotional development postulated a potential influence of prenatal
      hormonal levels or emotional stressors on child development [1-3]. In a
      retrospective study, an influence of maternal emotional stress on infant
      affective reactivity was found [4]. AIMS: this study was conducted in order to
      confirm these findings in a prospective study design. STUDY DESIGN: a prospective
      longitudinal study design was conducted with three study waves during pregnancy
      and one time point five months postnatally. SUBJECTS: the final sample consisted
      of n=104 mother-infant dyads. OUTCOME MEASURES: Maternal baseline cortisol levels
      and emotional stress were assessed in each trimester of pregnancy. Children were
      examined with the infant reactivity battery according to Kagan & Snidman [5] at
      the age of five months. RESULTS: mothers of children with high affective
      reactivity (cry score>=7) were significantly less depressed (p<.10) and perceived
      less stress (p<.05) in mid-pregnancy and were confronted with less external
      stress factors (p<.10) at the end of pregnancy. Cortisol levels did not differ in
      both groups in any pregnancy trimenon (p>.05). CONCLUSIONS: these data add a new
      specific aspect to the 'fetal programming hypothesis' and are the first to
      confirm the speculative data from retrospective studies. Baseline cortisol does
      not seem to be the 'hormonal mediator' of this association. Therefore, cortisol
      stress reactivity or other neuroendocrine mechanisms should be assessed in future
      studies.

PMID- 21194855
TI  - Executive function deficit in preschool children born very low birth weight with
      normal early development.
AB  - BACKGROUND: many studies showed that children born very low birth weight (VLBW)
      are at high risk of executive function (EF) deficit, including impulse control,
      working memory and cognitive flexibility. However, they did not exclude the
      influence of abnormal early development on EF deficit. AIMS: The aim was to
      investigate if six-year-old VLBW children with normal early development still
      have EF deficit. METHODS: the research was conducted in two groups. The VLBW
      group included 37 children at aged 6, with more than 70 of Bayley Scales of
      Infant Development-Second Edition (BSIDII) before aged 2. The normal group
      included 22 term children aged 6 who were born healthy and developed normally,
      with comparable IQ and social economic status. Five instruments, including
      Comprehensive Nonverbal Attention Test Battery (CNAT), Tower of London (ToL),
      Wisconsin Card Sorting Test (WCST), Knox's Cube Test and Digit Span Subtest of
      WISC-IV, were analyzed to evaluate four kinds of EF, including impulse control,
      planning, cognitive flexibility and working memory. RESULTS: the EF of VLBW group
      was significantly lower in independent t-test on the scores of planning in ToL,
      cognitive flexibility in WCST and nonverbal working memory in Knox's Cube Test.
      Yet, the inferiority in EF of VLBW group became less significant when ANCOVA
      analysis was used to adjust gestation age and birth weight. CONCLUSIONS: six-year
      old VLBW children even with normal early development are still at risk of
      deficits in "planning", "cognitive flexibility" and "nonverbal working memory"
      while the preterm factors, both gestation age and birth weight, were important
      covariant factors.

PMID- 21194856
TI  - Application of dispersive liquid-liquid microextraction and CE with UV detection
      for the chiral separation and determination of the multiple illicit drugs on
      forensic samples.
AB  - A new method was developed for pre-concentration, chiral separation and
      determination of multiple illicit drugs on forensic samples using dispersive
      liquid-liquid microextraction (DLLME) and capillary electrophoresis (CE) with
      Ultra Violet (UV) detection. The method was based on the formation of tiny
      droplets of an organic extractant in the prepared sample solution using water
      immiscible organic solvent (chloroform) dissolved in water-miscible organic
      dispersive solvent (isopropyl alcohol). The organic phase, which extracted
      heroin, DL-methamphetamine, DL-3, 4-methylenedioxymethamphetamine and dl-ketamine
      from the prepared sample solution, was separated by centrifuging. The sedimented
      phase was transferred into a small volume CE auto-sampler vial with 10 MUL of 1%
      HCl methanol solution and evaporated to dryness. The residue was reconstituted in
      lidocaine hydrochloride aqueous solution (internal standard) and introduced by
      electrokinetic injection into CE. Parameters affecting extraction efficiency were
      investigated and optimized. Under optimum conditions, linearity of the method was
      0.15-6500 MUg/L for all target analytes. The LODs (S/N=3) were 0.05-0.20 MUg/L.
      Excellent repeatability (RSD <= 4.4%, n=5) was achieved. The feasibility of this
      method was demonstrated by analyzing spiked forensic samples. To our knowledge,
      it is the first time to combine DLLME with CE for chiral separation and
      determining illicit drugs on forensic samples.

PMID- 21194857
TI  - Establishment of the measurement uncertainty of 11-nor-D9-tetrahydrocannabinol-9
      carboxylic acid in hair.
AB  - The quantitative analysis of 11-nor-D(9)-tetrahydrocannabinol-9-carboxylic acid
      (THCCOOH) in hair requires a sensitive method to detect a low-pg level. Before
      applying the method to real hair samples, the method was validated; in this
      study, we examined the uncertainty obtained from around the cut-off level of
      THCCOOH in hair. We calculated the measurement uncertainty (MU) of THCCOOH in
      hair as follows: specification of the measurand, identification of parameters
      using "cause and effect" diagrams, quantification of the uncertainty
      contributions using three factors, the uncertainty of weighing the hair sample,
      the uncertainty from calibrators and the calibration curve, and the uncertainty
      of the method precision. Finally, we calculated the degrees of freedom and the
      expanded uncertainty (EU). The concentration of THCCOOH in the hair sample with
      its EU was (0.60 +/- 0.1) * 10(-4)ng/mg. The relative uncertainty percent for the
      measurand 0.60 * 10(-4)ng was 9.13%. In this study, we also selected different
      concentrations of THCCOOH in real hair samples and then calculated the EU, the
      relative standard uncertainty (RSU) of the concentration of THCCOOH in the test
      sample [u(r)(c0)], the relative uncertainty percent, and the effective degree of
      freedom (v(eff)). When the concentrations of THCCOOH approached the cut-off
      level, u(r)(c0) and the relative uncertainty percent increased but absolute EU
      and v(eff) decreased.

PMID- 21194858
TI  - Profile of developmental delay in children under five years of age in a highly
      consanguineous community: a hospital-based study--Jordan.
AB  - AIM: To assess etiologies and risk factors for global developmental delay (GDD)
      in children. PATIENTS AND METHODS: Between January 2006 and 2007, a retrospective
      study was carried out at the Child Neurology Clinic of Jordan University Hospital
      on all 229 children under five years of age presenting with GDD. To assess risk
      factors for GDD, 229 age-matched healthy children were included as controls.
      RESULTS: A definite etiology for GDD could be determined in 102 (44.5%) patients,
      while 127 (55.5%) patients remained undiagnosed .The most common category for the
      GDD was cerebral palsy (CP) seen in 72 patients (31.4%), of which the underlying
      etiology was determined in 50 patients (69.5%). The second most common category
      was metabolic disorders where a definite metabolic cause was reached in 15 (6.5%)
      patients and a possible metabolic cause was suspected in 16 (6.9%) cases. Other
      etiologies included other monogenic disorders in 12 (5.2%) patients, brain
      malformations in 7 (3.0%) patients, chromosomal abnormalities in 6 (2.6%)
      patients, and autism in 12 (5.2%) patients. History of perinatal complications
      and consanguinity were major risk factors (p<0.05). CONCLUSION: To our knowledge
      this is the first and largest study on GDD in a highly consanguineous Arab
      population. Cerebral palsy and metabolic disorders were the most common causes of
      GDD in Jordan, while perinatal complications and consanguinity were the major
      risk factors contributing to GDD.

PMID- 21194859
TI  - Topiramate on the quality of life in childhood epilepsy.
AB  - This study evaluated the effect of topiramate (TPM) on the quality of life (QOL)
      in childhood epilepsy, using the Korean quality of life in childhood epilepsy (K
      QOLCE) questionnaire. An open label, prospective, observational study of the
      families of 664 children with epilepsy from 41 centers was conducted. The parents
      completed the K-QOLCE at the baseline visit and again 6months after starting TPM
      treatment. The parents reported the seizure frequency at both assessment dates.
      Statistically significant improvements in all K-QOLCE domains except social
      functioning were found at 6months after starting TPM treatment from the baseline
      scores (P<0.05). However, improved QOL scores were not dependent on the reduction
      in seizure frequency. TPM significantly improved QOL in children with epilepsy,
      suggesting its potential clinical benefits.

PMID- 21194860
TI  - [Plasmodium ovale malaria severity].

PMID- 21194861
TI  - [Clinical and epidemiological features of mycetoma in Morocco].

PMID- 21194862
TI  - [High frequency oscillation ventilation and extracorporeal membrane oxygenation
      during pernicious malaria].

PMID- 21194863
TI  - [Pulmonary actinomycosis].

PMID- 21194864
TI  - [Biological profile of adult patients infected with HIV at initiation of
      antiretroviral therapy in Togo].
AB  - OBJECTIVE: The study's objective was to determine the CD4 count and laboratory
      abnormalities in adults infected with HIV at initiation of antiretroviral therapy
      (ART) in Togo. METHODS: A retrospective and descriptive study was made of all
      patients on HAART in 2009 in Togo. RESULTS: A total of 5106 patients were
      included with a median age of 35 years. 68.6% were female patients. HIV1
      infection was predominant (97.5%). The mean CD4) count at treatment initiation
      was 134 cells/MUl. Among these patients, 22.1% had a CD4 count below 50 cells/MUl
      and 73.8% had a CD4 count below 200 cells/MUl. The median hemoglobin level was
      10.4 g/dl. Transaminase level was elevated (grade 1 and above) in 55.9% of
      patients for AST, and in 29.8% of patients for ALT. Mean serum creatinine was 9.6
      +/- 5 mg/l. CONCLUSION: Initiation of ART is late in Togo, consequently a
      significant proportion of patients present with severe immunosuppression on
      initiation of treatment. Improving strategies for mass screening should increase
      the number of patients treated early to better meet WHO 2009 recommendations.

PMID- 21194865
TI  - Adenosine-stress dynamic real-time myocardial perfusion CT and adenosine-stress
      first-pass dual-energy myocardial perfusion CT for the assessment of acute chest
      pain: initial results.
AB  - PURPOSE: Recent innovations in CT enable the evolution from mere morphologic
      imaging to dynamic and functional testing. We describe our initial experience
      performing myocardial stress perfusion CT in a clinical population with acute
      chest pain. METHODS AND MATERIALS: Myocardial stress perfusion CT was performed
      on twenty consecutive patients (15 men, 5 women; mean age 65 +/- 8 years) who
      presented with acute chest pain and were clinically referred for stress/rest
      SPECT and cardiac MRI. Prior to CT each patient was randomly assigned either to
      Group A or to Group B in a consecutive order (10 patients per group). Group A
      underwent adenosine-stress dynamic real-time myocardial perfusion CT using a
      novel "shuttle" mode on a 2nd generation dual-source CT. Group B underwent
      adenosine-stress first-pass dual-energy myocardial perfusion CT using the same CT
      scanner in dual-energy mode. Two experienced observers visually analyzed all CT
      perfusion studies. CT findings were compared with MRI and SPECT. RESULTS: In
      Group A 149/170 myocardial segments (88%) could be evaluated. Real-time perfusion
      CT (versus SPECT) had 86% (84%) sensitivity, 98% (92%) specificity, 94% (88%)
      positive predictive value, and 96% (92%) negative predictive value in comparison
      with perfusion MRI for the detection of myocardial perfusion defects. In Group B
      all myocardial segments were available for analysis. Compared with MRI, dual
      energy myocardial perfusion CT (versus SPECT) had 93% (94%) sensitivity, 99%
      (98%) specificity, 92% (88%) positive predictive value, and 96% (94%) negative
      predictive value for detecting hypoperfused myocardial segments. CONCLUSION: Our
      results suggest the clinical feasibility of myocardial perfusion CT imaging in
      patients with acute chest pain. Compared to MRI and SPECT both, dynamic real-time
      perfusion CT and first-pass dual-energy perfusion CT showed good agreement for
      the detection of myocardial perfusion defects.

PMID- 21194866
TI  - Tahibacter aquaticus gen. nov., sp. nov., a new gammaproteobacterium isolated
      from the drinking water supply system of Budapest (Hungary).
AB  - Three Gram-stain negative, aerobic, non-motile, non-spore-forming, rod-shaped
      bacterial strains, PYM5-11(T), RaM5-2 and PYM5-8, were isolated from the drinking
      water supply system of Budapest (Hungary) and their taxonomic positions were
      investigated by a polyphasic approach. All three strains grew optimally at 20-28
      degrees C and pH 5-7 without NaCl. The G+C content of the DNA of the type strain
      was 65.4mol%. On the basis of 16S rRNA gene sequence analysis, the isolates
      showed 94.5-94.9% sequence similarity to the type strain of Dokdonella koreensis
      and a similarity of 93.0-94.1% to the species of the genera Aquimonas and
      Arenimonas. The major isoprenoid quinone of the strains was ubiquinone Q-8. The
      predominant fatty acids were iso-C(15:0), iso-C(17:1)omega9c, C(16:1)omega7c, and
      C(16:0). Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine
      and phosphatidylmonomethylethanolamine, as well as several unidentified
      aminolipids and phospholipids were present. The 16S rRNA gene sequence analysis,
      the predominant fatty acids, the polar lipid composition, RiboPrint patterns,
      physiological and biochemical characteristics showed that the three strains were
      related but distinct from the type strains of the four recognized species of the
      genus Dokdonella, and indicated that the strains represented a new genus within
      the Gammaproteobacteria. The strain PYM5-11 (=DSM 21667(T)=NCAIM B 02337(T)) is
      proposed as the type strain of a new genus and species, designated as Tahibacter
      aquaticus gen. nov., sp. nov.

PMID- 21194867
TI  - Multilocus sequence analyses reveal several unnamed Mesorhizobium genospecies
      nodulating Acacia species and Sesbania sesban trees in Southern regions of
      Ethiopia.
AB  - Leguminous trees play an important role in agroforestry in Ethiopia, but studies
      of their rhizobial symbionts are scarce. In earlier studies, we surveyed natural
      nodulation of native leguminous trees growing in different agro-ecological zones
      in Southern Ethiopia, isolated 400 rhizobia, and characterized them based on
      different phenotypic and genotypic methods. In the present study we characterized
      18 strains belonging to the genus Mesorhizobium, isolated from nodules of Acacia
      abyssinica, A. senegal, A. tortilis and Sesbania sesban. Phylogenetic analysis of
      nearly full-length 16S rRNA gene grouped the test strains into three distinct
      clades separated from all currently recognized Mesorhizobium species. Three
      divergent strains formed separate branches while the other 15 strains formed
      three distinct groups, genospecies I-III. Grouping of the isolates under study
      based on the house-keeping genes recA, gyrB, rpoB and gltA were consistent and in
      agreement with that of 16S rRNA. Similarly phylogenetic relationships based on
      the symbiosis-related genes nodC, nodA and nifH were generally similar to those
      shown by the core genes, suggesting that these Acacia and Sesbania symbionts have
      a long history of separate evolution within Mesorhizobium. Cross inoculation
      experiments demonstrated a large variation in the ability of the test strains to
      elicit effective nodules. The Sesbania isolates, occupying a distinct clade in
      the nodC phylogenetic tree, formed effective nodules only with this host legume.
      The study strongly suggests that this collection of Mesorhizobium strains
      comprises several new species, and also indicates the role of the symbiotic genes
      in determining the host range of these bacteria.

PMID- 21194868
TI  - Recent advances in SPME techniques in biomedical analysis.
AB  - Biomedical analyses of drugs, metabolites, poisons, environmental and
      occupational pollutants, disease biomarkers and endogenous substances in body
      fluids and tissues are important in the development of new drugs, therapeutic
      monitoring, forensic toxicology, patient diagnosis, and biomonitoring of human
      exposure to hazardous chemicals. In these analyses, sample preparation is
      essential for isolation of desired components from complex biological matrices
      and greatly influences their reliable and accurate determination. Solid-phase
      microextraction (SPME) is an effective sample preparation technique that has
      enabled miniaturization, automation and high-throughput performance. The use of
      SPME has reduced assay times, as well as the costs of solvents and disposal. This
      review focuses on recent advances in novel SPME techniques, including fiber SPME
      and in-tube SPME, in biomedical analysis. We also summarize the applications of
      these techniques to pharmacotherapeutic, forensic, and diagnostic studies, and to
      determinations of environmental and occupational exposure.

PMID- 21194869
TI  - A new mixed mode solid phase extraction strategy for opioids, cocaines,
      amphetamines and adulterants in human blood with hybrid liquid chromatography
      tandem mass spectrometry detection.
AB  - A rapid method has been developed to analyse morphine, codeine, 6
      monoacetylmorphine, cocaine, benzoylecgonine, dihydrocodeine, cocaethylene, 3,4
      methylenedioxyamphetamine, ketamine, 3,4-methylenedioxymethamphetamine,
      pseudoephedrine, lignocaine, benzylpiperazine, methamphetamine, amphetamine,
      methadone, phenethylamine and levamisole in human blood. Blood samples were
      cleaned up using mixed mode solid phase extraction using EvoluteTM CX solid phase
      extraction cartridges and the sample aliquots were analysed by hybrid triple
      quadrupole linear ion trap (QTRAP) mass spectrometry with a runtime of 12.5 min.
      Multiple reaction monitoring (MRM) as survey scan and an enhanced product ion
      (EPI) scan as dependent scan were performed in an information-dependent
      acquisition (IDA) experiment. Finally, drug identification and confirmation was
      carried out by library search with a developed in-house MS/MS library based on
      EPI spectra at a collision energy spread of 35 +/- 15 in positive mode and MRM
      ratios. The method was validated in blood, according to the criteria defined in
      Commission Decision 2002/657/EC. At least two MRM transitions for each substance
      were monitored in addition to EPI spectra. Deuterated analogues of analytes were
      used as internal standards for quantitation where possible. The method proved to
      be simple and time efficient and was implemented as an analytical strategy for
      the illicit drug monitoring of opioids, cocaines, amphetamines and adulterants in
      forensic cases of crime offenders, abusers or victims in the Republic of Ireland.

PMID- 21194870
TI  - Ticagrelor versus clopidogrel in patients with acute coronary syndromes
      undergoing coronary artery bypass surgery: results from the PLATO (Platelet
      Inhibition and Patient Outcomes) trial.
AB  - OBJECTIVES: The purpose of this study is to evaluate the efficacy and safety of
      ticagrelor and clopidogrel in patients with acute coronary syndrome undergoing
      coronary artery bypass graft surgery (CABG), as a post-randomization strategy.
      BACKGROUND: Ticagrelor is a novel, reversibly binding, oral, direct-acting
      P2Y(12)-receptor antagonist. In the PLATO (Platelet Inhibition and Patient
      Outcomes) trial, which randomized 18,624 patients with acute coronary syndromes,
      ticagrelor compared with clopidogrel significantly reduced the risk of the
      primary composite end point of cardiovascular (CV) death, myocardial infarction,
      or stroke (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.77 to 0.92; p
      < 0.001). This report investigated the outcomes of patients treated with CABG
      during the trial. METHODS: In total, 1,899 patients underwent CABG post
      randomization. The protocol recommended ticagrelor/placebo to be withheld for 24
      to 72 h and clopidogrel/placebo for 5 days preoperatively. In all, 1,261 patients
      underwent CABG and were receiving study drug treatment <7 days before surgery.
      The statistical analysis was based on events occurring from the CABG procedure
      until the end of the study, excluding 3 patients with CABG after study end.
      RESULTS: In the 1,261 patient cohort, the relative reduction of primary composite
      end point at 12 months (10.6% [66 of 629] with ticagrelor versus 13.1% [79 of
      629] with clopidogrel; HR: 0.84; 95% CI: 0.60 to 1.16; p = 0.29) was consistent
      with the results of the whole trial. Total mortality was reduced from 9.7% (58 of
      629) to 4.7% (29 of 629; HR: 0.49; 95% CI: 0.32 to 0.77; p < 0.01), CV death from
      7.9% (47 of 629) to 4.1% (25 of 629; HR: 0.52; 95% CI: 0.32 to 0.85; p < 0.01),
      and non-CV death numerically from 2.0% to 0.7% (p = 0.07). There was no
      significant difference in CABG-related major bleeding between the randomized
      treatments. CONCLUSIONS: In the subgroup of patients undergoing CABG within 7
      days after the last study drug intake, ticagrelor compared with clopidogrel was
      associated with a substantial reduction in total and CV mortality without excess
      risk of CABG-related bleeding.

PMID- 21194871
TI  - Mechanisms potentially contributing to the reduction in mortality associated with
      ticagrelor therapy.

PMID- 21194872
TI  - Unraveling triadic communication in hospital consultations with adolescents with
      chronic conditions: the added value of mixed methods research.
AB  - OBJECTIVE: To integrate findings of a mixed methods research (MMR) into
      adolescents' preferences and competencies for communication during consultations,
      in order to demonstrate the added value of MMR for health communication research.
      METHODS: Sequential MMR with adolescents (12-19 years) with various chronic
      conditions in a university hospital. Methods comprised: (1) 31 face-to-face
      interviews; (2) Q-methodology; (3) 39 observations of outpatient consultations;
      (4) three focus groups with 27 healthcare providers; (5) web-based questionnaire
      in 960 adolescents. RESULTS: Adolescents had different preferences regarding
      health communication, but all wished to be involved as partners. Yet, their
      actual participation during consultations was low. They often acted as bystanders
      rather than main characters because their participation was neither requested nor
      encouraged. Parents filled the gap, to healthcare providers' frustration. The
      questionnaire confirmed the discrepancy between self-efficacy and self-reported
      independent behavior during consultations. CONCLUSION: Triadic communication was
      all but multi-party-talk and adolescents did not act and were not considered as
      main partners. MMR was of pivotal importance for our understanding. PRACTICE
      IMPLICATIONS: As chronically ill adolescents need to prepare themselves for
      transition to adult care, healthcare providers should encourage them to take the
      lead in communication by initiating independent visits and changing the parents'
      roles.

PMID- 21194873
TI  - Adrenocorticotropic hormone, but not trilostane, causes severe adrenal
      hemorrhage, vacuolization, and apoptosis in rats.
AB  - Adrenal necrosis has been reported as a complication of trilostane application in
      dogs with hyperadrenocorticism. One suspicion was that necrosis results from the
      increase of adrenocorticotropic hormone (ACTH) during trilostane therapy. The aim
      of the current study was to assess the effects of ACTH and trilostane on adrenal
      glands of rats. For experiment 1, 36 rats were divided into 6 groups. Groups 1.1
      to 1.4 received ACTH in different doses (60, 40, 20, and 10 MUg/d) infused
      subcutaneously with osmotic minipumps for 16 wk. Group 1.5 received saline, and
      group 1.6 received no therapy. For experiment 2, 24 rats were divided into 3
      groups. Group 2.1 and 2.2 received 5 and 50 mg/kg trilostane/d orally mixed into
      chocolate pudding for 16 wk. Eight control rats received pudding alone. At the
      end of the experiments, adrenal glands were assessed for necrosis by histology
      and immunohistochemistry; levels of endogenous ACTH and nucleosomes were assessed
      in the blood. Rats treated with 60 MUg ACTH/d showed more hemorrhage and
      vacuolization and increased numbers of apoptotic cells in the adrenal glands than
      rats treated with 20 or 10 MUg ACTH/d, trilostane, or control rats. Rats treated
      with 60 MUg ACTH/d had a higher amount of nucleosomes in the blood compared with
      rats treated with 10 MUg ACTH/d, trilostane, or saline. We conclude that in
      healthy rats ACTH, but not trilostane, causes adrenal degeneration in a dose
      dependent manner. Results of this study support the hypothesis that adrenal gland
      lesions seen in trilostane-treated dogs are caused by ACTH and not by trilostane.

PMID- 21194874
TI  - H-FABP and LEPR gene expression profile in skeletal muscles and liver during
      ontogenesis in various breeds of pigs.
AB  - The genes coding for H-FABP (heart acid-binding protein) and LEPR (leptin
      receptor) are considered to be candidates for lipid metabolism and thus affect
      fat deposition in pigs. The aim of our study was to assess the amount of H-FABP
      and LEPR transcript in the skeletal muscles (m. longissimus dorsi, m.
      semimembranosus) and liver of pigs of various ages. The experiments were carried
      out on 5 popular breeds of swine raised in Poland which exhibit different levels
      of fat tissue. Furthermore, we examined the effect of H-FABP and LEPR genotypes
      (HinfI, HpaII, and HaeIII for H-FABP and HpaII for LEPR) on the expression
      abundance of these genes. We confirmed a statistically significant relationship
      between the breed (P<.001), type of tissue (LEPR P<.001; H-FABP P<.01), and age
      of the animal (P<.05) on the abundance of mRNA transcript of both genes. In all
      breeds, the expression of the leptin receptor gene increased significantly
      (P<.01) with age in muscle tissue, whereas this relationship was not observed in
      liver tissue. However, the expression of the H-FABP gene in muscles did not
      change with age or breed, although in the liver expression levels were high in
      young (60 and 90 d) pigs. In conclusion, H-FABP and LEPR genes are strongly
      related to the development and function of fat tissue in pigs.

PMID- 21194875
TI  - Effects of weaning and syndyphalin-33 on expression of melanocortinergic appetite
      regulating genes in swine.
AB  - Syndyphalin-33 (SD-33) increases feed intake in sheep and recently weaned pigs.
      To assess the effects of SD-33 on hypothalamic gene expression, hypothalami were
      collected from unweaned pigs (n=19; 21+/-3 d of age) on day 0. Remaining pigs
      received an intramuscular injection of 0.5 MUmole/kg SD-33 (SD) or saline (VEH)
      and weaned into individual pens. On days 1, 4, and 7 after weaning, hypothalami
      were collected from subsets of pigs (n=8 or 9) within each treatment group.
      Expression of MU-opioid receptor (MOR) was less in SD pigs than in VEH pigs on
      day 1 and day 4, suggesting down-regulation of the receptor by SD-33. Expression
      of hypothalamic melanocortin 4 receptor (MC4R) at 1 d after weaning was increased
      in VEH pigs (but not SD pigs) relative to levels before weaning. Expression of
      AGRP was not significantly altered by weaning or treatment at 1 d after weaning.
      At 4 d after weaning, expression of AGRP was greater in SD pigs than in VEH pigs,
      but at day 7 expression was less in SD pigs than in VEH pigs. A strong positive
      correlation was noted between expression levels of MOR and MC4R across treatment
      and time. Treatment with SD-33 appeared to partially abrogate the effects of
      weaning on expression of two key appetite-regulating genes within 24 h. Effects
      of SD-33 appear to be mediated at least in part by the MU-opioid receptor and
      include actions on the melanocortinergic pathway.

PMID- 21194876
TI  - Ethanol withdrawal activates nitric oxide-producing neurons in anxiety-related
      brain areas.
AB  - The present study investigated whether nitric oxide (NO)-producing neurons
      localized in brain areas related to anxiety are also activated after ethanol
      withdrawal. Male Wistar rats were subjected to an oral ethanol self
      administration procedure, in which they were offered 6-8% (vol/vol) ethanol
      solution for a period of 21 days followed by abrupt discontinuation of the
      treatment. Control animals received control dietary fluid for similar periods of
      time. Twenty-four or 48 h after ethanol discontinuation, the animals were exposed
      to the open field for 10 min. Two hours later, their brains were removed and
      processed for Fos immunohistochemistry and nicotinamide adenine dinucleotide
      phosphate-diaphorase histochemistry (which is used to detect NO-producing
      neurons). Decreased exploratory activity was observed in animals subjected to 24
      h withdrawal, characterized by a shorter distance traveled in the open field.
      Additionally, increased Fos expression was detected in brain areas, such as the
      cingulate and piriform cortices, several hypothalamic nuclei, amygdaloid nuclei,
      most subdivisions of the periaqueductal gray matter, and dorsal raphe nucleus
      (DRN). Ethanol withdrawal activated NO-producing neurons in the paraventricular
      nucleus (PVN) of the hypothalamus, dorsolateral periaqueductal gray matter
      (DLPAG), and DRN. The results show that ethanol withdrawal activates NO-producing
      neurons in the PVN, DLPAG, and DRN, which are brain areas implicated in the
      modulation of emotional, autonomic, and motor expression of anxiety-like
      behaviors.

PMID- 21194877
TI  - Alcohol preference drinking in a mouse line selectively bred for high drinking in
      the dark.
AB  - We have selectively bred mice that reach very high blood ethanol concentrations
      (BECs) after drinking from a single bottle of 20% ethanol. High Drinking in the
      Dark (HDID-1) mice drink nearly 6g/kg ethanol in 4h and reach average BECs of
      more than 1.0mg/mL. Previous studies suggest that DID and two-bottle preference
      for 10% ethanol with continuous access are influenced by many of the same genes.
      We therefore asked whether HDID-1 mice would differ from the HS/Npt control stock
      on two-bottle preference drinking. We serially offered mice access to 3-40%
      ethanol in tap water versus tap water. For ethanol concentrations between 3 and
      20%, HDID-1 and HS/Npt controls did not differ in two-bottle preference drinking.
      At the highest concentrations, the HS/Npt mice drank more than the HDID-1 mice.
      We also tested the same mice for preference for two concentrations each of
      quinine, sucrose, and saccharin. Curiously, the mice showed preference ratios
      (volume of tastant/total fluid drunk) of about 50% for all tastants and
      concentrations. Thus, neither genotype showed either preference or avoidance for
      any tastant after high ethanol concentrations. Therefore, we compared naive
      groups of HDID-1 and HS/Npt mice for tastant preference. Results from this test
      showed that ethanol-naive mice preferred sweet fluids and avoided quinine but the
      genotypes did not differ. Finally, we tested HDID-1 and HS mice for an extended
      period for preference for 15% ethanol versus water during a 2-h access period in
      the dark. After several weeks, HDID-1 mice consumed significantly more than HS.
      We conclude that drinking in the dark shows some genetic overlap with other tests
      of preference drinking, but that the degree of genetic commonality depends on the
      model used.

PMID- 21194879
TI  - Clinical significance of tumor suppressor PTEN in colorectal carcinoma.
AB  - BACKGROUND: It has been demonstrated that the deletion, mutation,
      hypermethylation and subcellular location of the tumor suppressor phosphatase and
      tensin homologue (PTEN) are closely correlated with carcinogenesis, progression
      and prognosis of malignancy. Both mutation and the microsatellite instability of
      the PTEN gene influence regulation of the PI3K/Akt signaling pathway. This study
      investigated whether loss of nuclear PTEN is correlated with chemosensitivity,
      clinicopathological parameters and survival. METHODS: Intracellular levels of
      PTEN of multiple cell lines of colorectal carcinoma (CRC) were evaluated by
      Western blotting and immunocytochemistry. The chemosensitivity of cell lines with
      various expression levels of PTEN was evaluated using 5-flurouracil (5-FU),
      oxaliplatin and irinotecan (CPT), and clinical significance was evaluated by
      immunohistochemical analysis of 133 CRC specimens. RESULTS: Colon cancer cell
      lines HT-29, LoVo and SW480 differed in expression of PTEN, with high, moderate
      and low levels, respectively. HT-29 and LoVo PTEN expression was suppressed by a
      low concentration of 5-FU and oxaliplatin; however, SW480 was insensitive to
      these chemotherapeutic agents. Nuclear PTEN was overexpressed in most (>80%)
      normal colon mucosa samples, but the incidence significantly decreased (89.2% ->
      53.4%) in the CRC group. PTEN in the nucleus was negatively correlated with tumor
      size and vascular invasion in CRC, and CRC patients with negative PTEN expression
      in the nucleus exhibited poor survival. CONCLUSION: Cell lines with a high
      expression of PTEN are sensitive to chemotherapy with 5-FU and oxaliplatin.
      Nuclear PTEN expression gradually decreases after malignant transformation, and
      loss of PTEN expression in the nucleus is associated with tumor progression and
      poor clinical outcome in CRC.

PMID- 21194878
TI  - Altered anxiety-like behavior and long-term potentiation in the bed nucleus of
      the stria terminalis in adult mice exposed to chronic social isolation,
      unpredictable stress, and ethanol beginning in adolescence.
AB  - Alcohol and chronic stress exposure, especially during adolescence, can lead to
      an increased risk in adulthood of developing alcohol use disorders. To date,
      however, no study has assessed the potential long-term effects of chronic
      intermittent and unpredictable ethanol (EtOH) exposure in mice chronically
      stressed beginning in adolescence on brain function and anxiety-like behaviors in
      adulthood. In particular, alterations in function of the bed nucleus of the stria
      terminalis (BNST), a brain region heavily implicated in anxiety-related behaviors
      and altered plasticity following EtOH exposure, may play a key role in the
      pathological responses to chronic stress and EtOH. In the present study,
      adolescent and adult C57Bl/6J mice were exposed to a regimen of chronic social
      isolation and unpredictable stressors and EtOH (or air [sham]; CSI-CUS-EtOH and
      CSI-CUS-Sham, respectively) for 8-10 weeks. In adulthood, mice were tested for
      altered anxiety-like behavior (elevated plus maze [EPM] and modified social
      interaction [SI] test). Following behavioral testing, mice were reexposed to CSI
      CUS-EtOH (and CSI-CUS-Sham for controls) for an additional 3 days. Four to six
      hours following the final EtOH (or air) exposure, field potential recordings of
      the dorsal-lateral (dl)BNST were performed. Mice first exposed during adolescence
      to CSI-CUS-EtOH displayed lower levels of anxiety-like behavior on the EPM
      compared with mice first exposed to CSI-CUS-EtOH during adulthood and control
      mice only exposed to CSI-CUS-Sham, regardless of age of first exposure. However,
      mice first exposed to CSI-CUS-EtOH during adulthood displayed lower levels of
      anxiety-like behavior on the SI test compared with mice first exposed during
      adolescence and control CSI-CUS-Sham mice. CSI-CUS-EtOH exposure, regardless of
      age, produced blunted expression of long-term potentiation (LTP) in the dlBNST
      compared with CSI-CUS-Sham mice. This study demonstrates age-dependent effects of
      chronic unpredictable ethanol exposure in chronically stressed mice on anxiety
      like behaviors during adulthood. Further, CSI-CUS-EtOH exposure results in
      blunted LTP expression in the adult dlBNST.

PMID- 21194880
TI  - A comparison of three methods for nonpalpable breast cancer excision.
AB  - AIMS: To evaluate the efficacy of three methods of breast-conserving surgery
      (BCS) for nonpalpable invasive breast cancer in obtaining adequate resection
      margins and volumes of resection. MATERIALS AND METHODS: A total of 201
      consecutive patients undergoing BCS for nonpalpable invasive breast cancer
      between January 2006 and 2009 in four affiliated institutions was retrospectively
      analysed. Patients with pre-operatively diagnosed primary or associated ductal
      carcinoma in situ (DCIS), multifocal disease, or a history of breast surgery or
      neo-adjuvant treatment were excluded from the study. The resections were guided
      by wire localisation (WL), ultrasound (US), or radio-guided occult lesion
      localisation (ROLL). The pathology reports were reviewed to determine oncological
      margin status, as well as tumour and surgical specimen sizes. The optimal
      resection volume (ORV), defined as the spherical tumour volume with an added 1.0
      cm margin, and the total resection volume (TRV), defined as the corresponding
      ellipsoid, were calculated. By dividing the TRV by the ORV, a calculated
      resection ratio (CRR) was determined to indicate the excess tissue resection.
      RESULTS: Of all 201 excisions, 117 (58%) were guided by WL, 52 (26%) by US, and
      32 (16%) by ROLL. The rate of focally positive and positive margins for invasive
      carcinoma was significantly lower in the US group (N = 2 (3.7%)) compared to the
      WL (N = 25 (21.3%)) and ROLL (N = 8 (25%)) groups (p = 0.023). The median CRRs
      were 3.2 (US), 2.8 (WL) and 3.8 (ROLL) (WL versus ROLL, p < 0.05), representing a
      median excess tissue resection of 3.1 times the optimal resection volume.
      CONCLUSION: US-guided BCS for nonpalpable invasive breast cancer was more
      accurate than WL- and ROLL-guided surgery because it optimised the surgeon's
      ability to obtain adequate margins. The excision volumes were large in all
      excision groups, especially in the ROLL group.

PMID- 21194881
TI  - Total laparoscopic radical hysterectomy and pelvic lymphadenectomy in locally
      advanced stage IB2-IIB cervical cancer patients after neoadjuvant chemotherapy.
AB  - OBJECTIVE: To evaluate the feasibility and morbidity of total laparoscopic class
      C2 radical hysterectomy (TLRH) with pelvic lymphadenectomy in patients with
      locally advanced cervical cancer stage IB2 to IIB after neoadjuvant chemotherapy
      (NACT). METHODS: A prospective study was conducted from October 2004 to September
      2009. Cervical cancer patients, stage IB2-IIB with complete clinical response
      after 3 courses of NACT with paclitaxel 175 mg/m(2), ifosfamide 5 g/m(2) and
      cisplatin 75 mg/m(2) (TIP) underwent TLRH. RESULTS: Forty patients were included,
      with a median age of 46 years (range, 25-65), BMI of 24 kg/m(2) (range, 15-49).
      FIGO staging was IB2 in 23, IIA > 4 cm in 6 and IIB in 11 patients. Four patients
      required conversion to laparotomy. Pathological evaluation showed 9 complete
      response (pCR), 9 partial response (pPR1) with microscopic tumour, and 15 partial
      response (pPR2) with macroscopic tumour. Three patients had no response. The
      median operative time was 305 min (range, 215-430); the median estimated blood
      loss was 250 ml (range, 100-400), with four postoperative blood transfusion; the
      median number of removed pelvic lymph nodes was 25 (range, 11-64). The median
      length of hospital stay was 6 days (range, 3-12). The median follow-up time was
      37 months (range, 10-69), with three patients having a recurrence. One patient
      died of disease (DOD) after 12 months. CONCLUSIONS: TLRH can be safely performed
      in patients with stage IB2-IIB carcinoma of cervix after NACT, with advantages of
      minimal blood loss and morbidity.

PMID- 21194882
TI  - Imperatorin a furocoumarin inhibits periplasmic Cu-Zn SOD of Shigella dysenteriae
      their by modulates its resistance towards phagocytosis during host pathogen
      interaction.
AB  - Shigella dysenteriae continues to be a major health problem, which leads to
      death, due to diarrhoea and dysentery, predominantly in children below the age of
      5. Bacterial invasion of the colonic epithelium leads to severe inflammation
      together with bacterial dissemination generates abscesses and ulcerations.
      Periplasmic copper, zinc super oxide dismutase of Shigella protects it from
      exogenous superoxide produced by host, during its invasion. Hence, in present
      study an attempt was made to study the effect of aqueous extract of Aegle
      marmelos on host and pathogen defence. Histology analysis of rat ileal loop
      showed the loss of virulence in aqueous extract of A. marmelos pre-treated
      Shigella and their intracellular survival was also decreased, where active
      component present in aqueous extract of A. marmelos was identified as imperatorin
      confirmed by UV absorption spectrum and HPLC. Increase in peripheral blood
      mononuclear cell viability and decreased in intracellular bacterial count along
      with transmission electron microscope analysis of imperatorin treated S.
      dysenteriae succumb to host oxidative stress. Loss of virulence is associated
      with attenuation of copper, zinc super oxide dismutase activity in Shigella,
      which was confirmed by using activity staining of bacterial cell lysate. Further,
      by performing docking analysis it has been proved that imperatorin present in
      aqueous extract of A. marmelos inhibited copper, zinc super oxide dismutase. From
      the above study, we concluded that Shigella succumb to oxidative stress (host
      defence) due to inhibition of copper, zinc super oxide dismutase (pathogen's
      defence) by imperatorin, an active compound aqueous extract of A. marmelos.

PMID- 21194883
TI  - Pulmonary manifestations of Sjogren's syndrome.
AB  - Sjogren's syndrome is a chronic inflammatory disorder characterized by
      lymphocytic infiltration of exocrine glands, mainly the lacrimal and salivary
      glands. However, extraglandular organ systems may frequently be involved,
      including the lungs. Although subclinical pulmonary inflammation exists in more
      than 50% of patients, clinically significant pulmonary involvement affects
      approximately 10% of patients and may be the first manifestation of the disease.
      The entire respiratory tract may be involved, with a wide spectrum of
      manifestations including xerotrachea and bronchial sicca, obstructive small
      airway disease, various patterns of interstitial lung disease, lymphoinfiltrative
      or lymphoproliferative lung disease, such as lymphoma (usually of MALT type),
      pulmonary hypertension, pleural involvement, lung cysts, and pulmonary
      amyloidosis.

PMID- 21194884
TI  - Pleural and pulmonary involvement in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a rare complex autoimmune disease with a
      multisystem involvement. The clinical manifestations of this disease include an
      erythematous rash, oral ulcers, polyarthralgia, nonerosive arthritis,
      polyserositis, hematologic, renal, neurologic, pulmonary and cardiac
      abnormalties. The involvement of the respiratory system is frequent. Pleuro
      pulmonary manifestations are present in almost half of the patients during the
      disease course and may be the presenting symptoms in 4-5% of patients with SLE.
      Complications directly associated to the disease include pleuritis with or
      without pleural effusion, alveolitis, interstitial lung disease, lupus
      pneumonitis, pulmonary hemorrhage, pulmonary arterial hypertension, and pulmonary
      thromboembolic disease. Complications due to secondary causes include pleuro
      pulmonary manifestations of cardiac and renal failure, atelectasis due to
      diaphragmatic dysfunction, opportunistic pneumonia, and drug toxicity. The
      prevalence, clinical presentation, prognosis and response to treatment vary,
      depending on the pattern of involvement. As with other connective tissue
      diseases, early and specific therapeutic intervention may be indicated for many
      of these pleuro-pulmonary manifestations.

PMID- 21194885
TI  - High-resolution echocardiographic assessment of infarct size and cardiac function
      in mice with myocardial infarction.
AB  - BACKGROUND: The aim of this study was to develop a simple and reasonably precise
      echocardiographic method for the assessment of infarct size (IS) and cardiac
      dysfunction in mice after myocardial infarction. METHODS: In vivo experiments
      were performed in C57BL/6J wild-type mice (n = 18) before and 48 hours after left
      anterior descending coronary artery ligation. Endocardial length-based
      echocardiographic IS was validated with that by three different histologic
      measurements. Left ventricular function was evaluated. RESULTS: Excellent
      agreement was found between endocardial length-based echocardiographic
      measurement and angle-based histologic measurement of IS (r = 0.82, P < .001),
      and both methods strongly correlated with Tei index (r = 0.82, P < .001, and r =
      0.74, P < .01) and fractional area change (r = -0.61, P < .05, and r = -0.81, P <
      .001). CONCLUSIONS: Endocardial length-based echocardiographic measurement proved
      to be a useful method for assessing myocardial IS and is applicable for
      biomedical and imaging research, and appears particularly promising in studies of
      left ventricular remodeling after myocardial infarction.

PMID- 21194886
TI  - Beyond publication bias.
AB  - In drug development, clinical medicine, or health policy making, basing one's
      decisions on a selective part of the available evidence can pose a major threat
      to the health of patients and the society. If, for example, primarily positive
      research reports are taken into account, one could wrongfully conclude that a
      harmful drug is safe. The systematic error introduced by summarizing evidence
      that is not representative of the available evidence is commonly referred to as
      "publication bias." Some, however, prefer other terms to refer to the same
      concept. In this article, we explore the terminology and concepts relevant to
      this bias and propose a more systematic nomenclature than what is currently used.

PMID- 21194887
TI  - Improving the measurement of self-reported medication nonadherence.
AB  - OBJECTIVE: Medication nonadherence is a significant clinical problem in chronic
      disease management. Self-report measures have inadequate reliability and poor
      distributional properties. We demonstrate how two fundamental measurement issues
      have limited the usefulness of self-reported medication nonadherence measures and
      offer recommendations for improving measurement. STUDY DESIGN AND METHODS: We
      reviewed existing self-report measures of medication nonadherence in the context
      of hypertension, one of the most common chronic conditions in which medication
      nonadherence is a paramount concern. We evaluated these measures with regard to
      two issues: (1) conflation of causal indicators (which give rise to a latent
      construct) and effect indicators (which are determined by a latent construct),
      and (2) a lack of evidence regarding the stability of nonadherence over time.
      RESULTS: Nonadherence measurement could be improved by using effect indicators to
      assess the extent of nonadherence and causal indicators to assess reasons for
      nonadherence. Moreover, nonadherence should be assessed longitudinally, so that
      recent developments in statistical modeling can illuminate the extent to which
      medication nonadherence is transient vs. stable. CONCLUSION: Attention to these
      measurement issues can improve the assessment of self-reported nonadherence,
      thereby allowing more accurate conclusions to be drawn about medication-taking
      behavior and informing the development of improved interventions that target
      medication nonadherence.

PMID- 21194888
TI  - Trade-off between benefit and harm is crucial in health screening
      recommendations. Part II: evidence summaries.
AB  - Evidence on the effectiveness of health screening strategies may be direct (i.e.,
      studies on screening vs. no screening) or indirect (i.e., studies that separately
      evaluate the screening test[s], the confirmatory test, or the treatment).
      Critical trade-offs in the balance between harm and benefit for many screening
      strategies mandate that advocates of health screening adhere to the ethical
      precepts of nonmaleficence, autonomy, confidentiality, and equity. In our first
      article, we pointed out five prerequisites to justifying a health screening
      program: (1) the burden of illness should be high, (2) the screening and
      confirmatory tests should be accurate, (3) early treatment (or prevention) must
      be more effective than late treatment, (4) the tests and the treatment(s) must be
      safe, and (5) the cost of the screening strategy must be commensurate with the
      potential benefit. As can be gleaned from these criteria, recommendations on
      screening must be tailored to specific populations. Recommendations in one
      country, no matter how authoritative, cannot be generalized to apply to all other
      countries. Although accuracy, effectiveness, and safety data may be global
      (criteria 2-4), burden of illness and efficiency (criteria 1 and 5) will always
      vary from country to country. Rather than review various national guidelines, in
      this last article of our two-part series, we present evidence summaries to
      illustrate health screening. Our examples were selected to address special issues
      related to four situations-screening for cancer, risk factors for disease,
      genetic disorders, and infectious diseases.

PMID- 21194889
TI  - Development and use of reporting guidelines for assessing the quality of
      validation studies of health administrative data.
AB  - BACKGROUND AND OBJECTIVES: Validation of health administrative data for
      identifying patients with different health states (diseases and conditions) is a
      research priority, but no guidelines exist for ensuring quality. We created
      reporting guidelines for studies validating administrative data identification
      algorithms and used them to assess the quality of reporting of validation studies
      in the literature. METHODS: Using Standards for Reporting of Diagnostic accuracy
      (STARD) criteria as a guide, we created a 40-item checklist of items with which
      identification accuracy studies should be reported. A systematic review
      identified studies that validated identification algorithms using administrative
      data. We used the checklist to assess the quality of reporting. RESULTS: In 271
      included articles, goals and data sources were well reported but few reported
      four or more statistical estimates of accuracy (36.9%). In 65.9% of studies
      reporting positive predictive value (PPV)/negative predictive value (NPV), the
      prevalence of disease in the validation cohort was higher than in the
      administrative data, potentially falsely elevating predictive values. Subgroup
      accuracy (53.1%) and 95% confidence intervals for accuracy measures (35.8%) were
      also underreported. CONCLUSIONS: The quality of studies validating health states
      in the administrative data varies, with significant deficits in reporting of
      markers of diagnostic accuracy, including the appropriate estimation of PPV and
      NPV. These omissions could lead to misclassification bias and incorrect
      estimation of incidence and health services utilization rates. Use of a reporting
      checklist, such as the one created for this study by modifying the STARD
      criteria, could improve the quality of reporting of validation studies, allowing
      for accurate application of algorithms, and interpretation of research using
      health administrative data.

PMID- 21194890
TI  - Trade-off between benefit and harm is crucial in health screening
      recommendations. Part I: general principles.
AB  - Health screening is defined as the use of a test or a series of tests to detect
      unrecognized health risks or preclinical disease in apparently healthy
      populations to permit prevention and timely intervention. A health screening
      strategy consists of the sequence of a screening test, confirmatory test(s), and
      finally, treatment(s) for the condition detected. The potential benefits of
      health screening are easy to understand, but the huge potential for physical and
      psychological harm is less well recognized. Thus, health screening should only be
      recommended when five criteria are satisfied: (1) the burden of illness should be
      high, (2) the tests for screening and confirmation should be accurate, (3) early
      treatment (or prevention) must be more effective than late treatment, (4) the
      test(s) and treatment(s) must be safe, and (5) the cost of the screening strategy
      must be commensurate with potential benefit. Direct evidence from screening
      trials is subject to less bias. In some instances, indirect evidence may be
      acceptable, e.g., when the condition screened for is a risk factor for a disease
      rather than the disease itself.

PMID- 21194891
TI  - GRADE guidelines: 2. Framing the question and deciding on important outcomes.
AB  - GRADE requires a clear specification of the relevant setting, population,
      intervention, and comparator. It also requires specification of all important
      outcomes--whether evidence from research studies is, or is not, available. For a
      particular management question, the population, intervention, and outcome should
      be sufficiently similar across studies that a similar magnitude of effect is
      plausible. Guideline developers should specify the relative importance of the
      outcomes before gathering the evidence and again when evidence summaries are
      complete. In considering the importance of a surrogate outcome, authors should
      rate the importance of the patient-important outcome for which the surrogate is a
      substitute and subsequently rate down the quality of evidence for indirectness of
      outcome.

PMID- 21194892
TI  - Comparative evaluation of 2.0-mm locking plate system vs 2.0-mm nonlocking plate
      system for mandibular fracture: a prospective randomized study.
AB  - This study evaluated the efficacy of a 2.0-mm locking plate/screw system compared
      with a 2.0-mm non-locking plate/screw system in mandibular fractures. A
      prospective randomized clinical trial was conducted. Patients were randomly
      assigned to receive 2.0-mm locking plates (group A) or 2.0-mm nonlocking plates
      (group B). All patients were followed up for 12 weeks postoperatively.
      Complications were analysed according to the type of plate used and the site of
      fracture. Fifty patients with 76 fractures met the inclusion criteria. Thirty-six
      fracture sites were treated with 2.0-mm locking plates and 40 with 2.0-mm
      nonlocking plates. The number of patients requiring postoperative
      maxillomandibular fixation was significantly higher in group B (p < 0.01); seven
      complications occurred representing 9% of the total. Two complications occurred
      in the locking group and five in the nonlocking group with complication rates
      equalling 6% and 13%, respectively. When comparing the overall complication rates
      according to plates used, the chi(2) test showed no statistically significant
      difference between the locking and nonlocking plates (p > 0.05). In conclusion,
      mandible fractures treated with 2.0-mm locking plates and 2.0-mm nonlocking
      plates present similar short-term complication rates.

PMID- 21194893
TI  - MMN responsivity to manipulations of frequency and duration deviants in chronic,
      clozapine-treated schizophrenia patients.
AB  - Event-related potential (ERP) probing of abnormal sensory processes in
      schizophrenia with the mismatch negativity (MMN) has shown impairments in
      auditory change detection, but knowledge of the acoustic features leading to this
      deficit is incomplete. Changes in the duration and frequency properties of sound
      stimuli result in diminished MMNs in schizophrenia but it is unclear as to
      whether this reduced responsiveness is seen with more subtle changes in sound
      frequency. In a sample of 19 healthy controls and 21 patients with chronic
      schizophrenia treated with clozapine, MMN was assessed in response to tone
      frequency changes of 5%, 10% and 20%, and to tone duration changes. Patients
      exhibited reduced amplitudes and shorter latencies than controls to all frequency
      changes, and attenuated amplitudes to tone duration increments and decrements.
      Clozapine dose was related to MMN, with increasing dose being positively
      associated with frequency-MMN amplitudes (10% ?f, 20% ?f) and negatively
      associated with the amplitude and latency of duration-MMNs. These data support
      the well-established findings of auditory sensory abnormality in schizophrenia
      and underscore the sensitivity of MMN to relatively small auditory change
      detection deficits that may appear to characterize chronic schizophrenia.

PMID- 21194894
TI  - Executive function in first-episode schizophrenia: a three-year longitudinal
      study of an ecologically valid test.
AB  - Executive function impairment is a key cognitive deficit in schizophrenia.
      However, traditional neuropsychological tests of executive function may not be
      sensitive enough to capture the everyday dysexecutive problems experienced by
      patients. Additionally, existing literature has been inconsistent about
      longitudinal changes of executive functions in schizophrenia. The present study
      focuses on examining the longitudinal change of executive functions in
      schizophrenia using the Modified Six Elements Test (MSET) that was developed
      based on the Supervisory Attentional System model and shown to be sensitive to
      everyday dysexecutive problems. In the present study, MSET performance was
      assessed in 31 medication-naive first-episode schizophrenic patients at four
      times over a period of three years, while the 31 normal controls were assessed
      once. Patients demonstrated impairment in MSET as compared to controls.
      Importantly, the MSET impairment persisted from the medication-naive state to
      clinical stabilization and the three years following the first psychotic episode
      though patients improved in a conventional executive test (Modified Wisconsin
      Card Sorting Test). Performance was not related to intelligence, educational
      level, symptom changes, age-of-onset, or duration of untreated psychosis. Better
      MSET performance at medication-naive state predicted improvement in negative and
      positive symptoms over the three-year period. These findings may suggest that
      MSET impairment is a primary deficit in schizophrenia that occurs early in the
      course of the illness and remains stable irrespective of clinical state for at
      least three years following the first episode of schizophrenia.

PMID- 21194895
TI  - Medicinal plant extracts with efflux inhibitory activity against Gram-negative
      bacteria.
AB  - It was hypothesised that extracts from plants that are used as herbal medicinal
      products contain inhibitors of efflux in Gram-negative bacteria. Extracts from 21
      plants were screened by bioassay for synergy with ciprofloxacin against
      Salmonella enterica serotype Typhimurium, including mutants in which acrB and
      tolC had been inactivated. The most active extracts, fractions and purified
      compounds were further examined by minimum inhibitory concentration testing with
      five antibiotics for activity against Enterobacteriaceae and Pseudomonas
      aeruginosa. Efflux activity was determined using the fluorescent dye Hoechst
      33342. Eighty-four extracts from 21 plants, 12 fractions thereof and 2 purified
      molecules were analysed. Of these, 12 plant extracts showed synergy with
      ciprofloxacin, 2 of which had activity suggesting efflux inhibition. The most
      active extract, from Levisticum officinale, was fractionated and the two
      fractions displaying the greatest synergy with the five antibiotics were further
      analysed. From these two fractions, falcarindiol and the fatty acids oleic acid
      and linoleic acid were isolated. The fractions and compounds possessed
      antibacterial activity especially for mutants lacking a component of AcrAB-TolC.
      However, no synergism was seen with the fractions or purified molecules,
      suggesting that a combination of compounds is required for efflux inhibition.
      These data indicate that medicinal plant extracts may provide suitable lead
      compounds for future development and possible clinical utility as inhibitors of
      efflux for various Gram-negative bacteria.

PMID- 21194896
TI  - Early post-stressor intervention with propranolol is ineffective in preventing
      posttraumatic stress responses in an animal model for PTSD.
AB  - The therapeutic value of beta-adrenoceptor blockage, using propranolol, in the
      aftermath of traumatic experience is uncertain. A prospective, controlled animal
      model of posttraumatic stress disorder (PTSD) was employed to assess the effects
      of propranolol on long-term behavioral responses to stress. Animals exposed to
      predator scent stress received a single bolus of propranolol (10 or 15mg/kg) or
      vehicle 1h post-exposure. Outcomes were assessed using the elevated plus-maze
      (EPM) and acoustic startle response (ASR) at 30days and freezing response to a
      trauma reminder (unsoiled litter) on Day 31. Individual animals were classified
      as having "extreme", "partial" and "minimal" behavioral responses, according to
      pre-set cut-off criteria for EPM and ASR response patterns. The physiological
      efficacy of the doses of propranolol was verified by collecting cardiovascular
      data telemetrically (from exposed or unexposed individuals given propranolol or
      vehicle). The effect of propranolol on long-term memory was verified using a non
      spatial memory task. Both doses of propranolol effectively reduced mean heart
      rate and impaired the object-recognition task, as expected. No significant effect
      on prevalence rates of PTSD-like behavioral responses or on trauma reminder
      response was observed for either dose of propranolol as compared to vehicle.
      Despite adequate efficacy in terms of heart rate and disruption of memory, single
      dose, post-stress beta-blockage with propranolol was ineffective in reducing
      onset of PTSD-like behavioral disruption and trauma cue responses in the long
      term. Traumatic stress-related processes appear to be affected differently than
      the others.

PMID- 21194897
TI  - Pragmatic measures in paediatric psychopharmacology--are we getting it right?
AB  - Recent changes in legislation have stimulated a new wave of interest and activity
      in paediatric psychopharmacology. This increased activity has coincided with a
      recognition that pragmatic measures of outcome such as those that tap into
      impairment and health related quality of life (HRQOL) have the potential to add
      considerably to the traditional symptom based measures of outcome. There are
      however considerable methodological issues associated with these types of
      measure, and these are made more complex when they are applied in mental health
      and paediatric settings. There is a clear need for the continued development of
      valid and reliable measures of HRQOL and impairment that are fit for purpose for
      use in clinical trials. Other more specific issues that need to be considered,
      and which all require further investigation include those relating to; age, self
      versus proxy ratings, contextual issues, generic versus disorder specific
      measures and definitions of clinically meaningful change. Most of the child and
      adolescent mental health trials that have included pragmatic measures have been
      conducted in ADHD samples, have been industry sponsored, use only parent ratings
      and focus on one drug (atomoxetine). Taken together they do however suggest that
      pharmacological treatments can impact positively on impairment and HRQOL,
      although with smaller effect sizes than is seen for symptom reduction. Further
      studies, across a wider range of disorders and treatments with multiple measures
      and multiple raters, are to be encouraged. In addition to reporting the basic
      outcomes from these studies researchers should use these data to improve the
      measurement models and refine both the measures and the trial designs.

PMID- 21194899
TI  - High antibacterial efficiency of pDMAEMA modified silicon nanowire arrays.
AB  - Materials of high antibacterial activity based on quaternized poly (2
      (dimethylamino ethyl) methacrylate) (pDMAEMA) have been developed. DMAEMA was
      graft polymerized on silicon nanowire arrays (SiNWAs) by atom transfer radical
      polymerization (ATRP), and quaternized using benzyl chloride. The graft density
      on the modified nanowire arrays was much higher than on analogous smooth silicon,
      leading to higher bacterial adhesion on the nanowire arrays (34.6+/-0.39*10(6)
      vs. 5.0+/-0.15*10(6) cells/cm(2)). Incubation of Escherichia coli on the
      substrates for 18 h resulted in 95% cell death on the quaternized nanowire
      material compared to less than 45% on the quaternized smooth silicon. The results
      suggest that silicon nanowire array modified with quaternized pDMAEMA is a highly
      effective antibacterial material due to a high density of antibacterial polymer
      and consequent high bacterial adhesion and killing.

PMID- 21194898
TI  - A selective neurokinin-1 receptor antagonist in chronic PTSD: a randomized,
      double-blind, placebo-controlled, proof-of-concept trial.
AB  - The substance P-neurokinin-1 receptor (SP-NK(1)R) system has been extensively
      studied in experimental models of stress, fear, and reward. Elevated
      cerebrospinal fluid (CSF) SP levels were reported previously in combat-related
      PTSD. No medication specifically targeting this system has been tested in PTSD.
      This proof-of-concept randomized, double-blind, placebo-controlled trial
      evaluated the selective NK(1)R antagonist GR205171 in predominately civilian
      PTSD. Following a 2-week placebo lead-in, 39 outpatients with chronic PTSD and a
      Clinician-Administered PTSD Scale (CAPS) score >=50 were randomized to a fixed
      dose of GR205171 (N=20) or placebo (N=19) for 8weeks. The primary endpoint was
      mean change from baseline to endpoint in the total CAPS score. Response rate
      (>=50% reduction in baseline CAPS) and safety/tolerability were secondary
      endpoints. CSF SP concentrations were measured in a subgroup of patients prior to
      randomization. There was significant improvement in the mean CAPS total score
      across all patients over time, but no significant difference was found between
      GR205171 and placebo. Likewise, there was no significant effect of drug on the
      proportion of responders [40% GR205171 versus 21% placebo (p=0.30)]. An
      exploratory analysis showed that GR205171 treatment was associated with
      significant improvement compared to placebo on the CAPS hyperarousal symptom
      cluster. GR205171 was well-tolerated, with no discontinuations due to adverse
      events. CSF SP concentrations were positively correlated with baseline CAPS
      severity. The selective NK(1)R antagonist GR205171 had fewer adverse effects but
      was not significantly superior to placebo in the short-term treatment of chronic
      PTSD. (ClinicalTrials.gov Identifier: NCT 00211861, NCT 00383786).

PMID- 21194900
TI  - Colon specific chitosan microspheres for chronotherapy of chronic stable angina.
AB  - In the present work, chitosan microspheres with a mean diameter between 6.32 MUm
      and 9.44 MUm, were produced by emulsion cross-linking of chitosan, and tested for
      chronotherapy of chronic stable angina. Aiming at developing a suitable colon
      specific strategy, diltiazem hydrochloride (DTZ) was encapsulated in the
      microspheres, following Eudragit S-100 coating by solvent evaporation technique,
      exploiting the advantages of microbiological properties of chitosan and pH
      dependent solubility of Eudragit S-100. Different microsphere formulations were
      prepared varying the ratio DTZ:chitosan (1:2 to 1:10), stirring speed (1000-2000
      rpm), and the concentration of emulsifier Span 80 (0.5-1.5% (w/v)). The effect of
      these variables on the particle size and encapsulation parameters (production
      yield (PY), loading capacity (LC), encapsulation efficiency (EE)) was evaluated
      to develop an optimized formulation. In vitro release study of non-coated
      chitosan microspheres in simulated gastrointestinal (GI) fluid exhibited a burst
      release pattern in the first hour, whereas Eudragit S-100 coating allowed
      producing systems of controlled release diffusion fitting to the Higuchi model,
      and thus suitable for colon-specific drug delivery. DSC analysis indicated that
      DTZ was dispersed within the microspheres matrix. Scanning electron microscopy
      revealed that the microspheres were spherical and had a smooth surface. Chitosan
      biodegradability was proven by the enhanced release rate of DTZ in presence of
      rat caecal contents.

PMID- 21194901
TI  - Impact of interfacial composition on emulsion digestion and rate of lipid
      hydrolysis using different in vitro digestion models.
AB  - A sequential in vitro model of digestion was used to investigate the changes in
      the physicochemical properties of emulsions during gastrointestinal transit. Oil
      in-water emulsions were prepared with whey protein isolate (WPI) or soy protein
      isolate (SPI) at the same protein concentration (1.5%). Despite pepsinolysis of
      both proteins during the gastric phase, emulsions stabilized with WPI were more
      stable compared to those prepared with SPI. For both emulsions, the size of the
      oil droplets, which plays a critical role in lipid digestion, was extensively
      altered during the duodenal phase due to the presence of bile salts (BS) and
      phospholipids (PL). As shown by zeta-potential measurements, the results
      suggested the displacement of both proteins from the interface by BS; however,
      the displacement was much faster for the WPI-emulsions. The change in interfacial
      composition of the oil droplets was significantly affected by inclusion of PL and
      phospholipase A(2) (PLA(2)) in the in vitro digestion model. The interfacial
      activity of pancreatic triglyceride lipase (PTL) was markedly affected in the
      presence of the surface-active compounds present in the digestive fluids,
      including BS, PL, colipase (COL) and PLA(2). A higher percentage of lipid
      hydrolysis was obtained in the presence of COL and PLA(2) than with BS alone or
      mixed BS-PL. SPI-emulsions consistently showed a higher degree of lipolysis
      compared to the WPI-emulsions regardless of the in vitro digestion model used.
      The results support the conclusion that the interfacial composition of the
      original emulsion plays a major role in determining the extent of lipolysis.

PMID- 21194902
TI  - Physicochemical properties of nevirapine-loaded solid lipid nanoparticles and
      nanostructured lipid carriers.
AB  - Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) coated
      with human serum albumin (HSA) were fabricated for formulating nevirapine (NVP).
      Here, NLCs contained low-melting-point oleic acid (OA) in the internal lipid
      phase. The results revealed that the two nanoparticles were uniformly distributed
      with the average diameter ranging from 145 to 180 nm. The surface HSA neutralized
      the positive charge of dimethyldioctadecyl ammonium bromide (DODAB) on SLNs and
      NLCs and reduced their zeta potential. In a fixed ratio of solid lipids, SLNs
      entrapped more NVP than NLCs. The incorporation of OA also reduced the thermal
      resistance of NLCs and accelerated the release of NVP from the nanocarriers. When
      incubated with DODAB-stabilized SLNs, the viability of human brain-microvascular
      endothelial cells (HBMECs) reduced. However, the surface HSA increased the
      viability of HBMECs about 10% when the concentration of SLNs was higher than 0.8
      mg/mL. HSA-grafted SLNs and NLCs can be effective formulations in the delivery of
      NVP for viral therapy.

PMID- 21194903
TI  - [Fetomaternal anti-RH3, -4 (anti-E and anti-c) rhesus isoimmunization: a case
      report].
AB  - Hemolytic disease of the newborn caused by maternal isoimmunization has been
      decreasing over the past 10 years because of prophylactic treatment with anti-RH1
      (anti-D) immunoglobulin. Nevertheless, there is an increase in the incidence of
      both relative and absolute numbers of non-RH1 red-cell maternofetal
      isoimmunizations, essentially anti-RH4 (anti-c), anti-RH3 (anti-E), and anti
      Kell. In 8 to 14% of cases, multispecificity antibodies are present, the most
      common combination being the association of anti-RH3 and -4. Despite absence of
      specific prophylactic therapy, anti-RH4 isoimmunization could be as severe as
      anti-RH1 ; as for anti-RH3, it is usually associated with mild to moderate
      clinical manifestations. Nevertheless, there are few publications on anti-RH3, -4
      maternofetal isoimmunization with a bias toward the most severe cases being
      reported. We report here a case of nonsevere maternofetal anti-RH3, -4
      isoimmunization complicated with severe hyperbilirubinemia and delayed profound
      anemia. Hyperbilirubinemia was controlled using intensive phototherapy. Although
      anemia was absent at birth, it appeared progressively with a nadir at 7.8 g/dL at
      1-month postnatal age. Blood counts were monitored for 3 months but the patient
      did not require red blood cell transfusion. This report underlines the need for a
      prolonged and rigorous pediatric follow-up of children born in the context of
      maternofetal isoimmunization after the acute neonatal period. Furthermore, it
      stresses the necessity of DAT testing in all pregnant women, even those who are
      RH1-positive.

PMID- 21194904
TI  - [Difficult transitions from paediatric to adult care in type 1 Gaucher disease].
AB  - Gaucher disease is the most frequent lysosomal storage disease. It is a
      progressive chronic disease that can lead to substantial bone and joint damage
      and hematological cytopenias. This progressive disease severely worsens the
      patients' quality of life. Over the past 20 years, enzymatic treatment has
      considerably improved both symptoms and quality of life. Yet, bone and joint
      damage may be irreversible. This emphasizes the importance of rigorous follow-up
      so as to begin uninterrupted treatment before lesion onset. The transition from
      pediatric to adult care is a major concern for chronic patients. This step is
      often associated with follow-up problems and may lead to disease worsening. We
      present three cases of patients who were lost to follow-up during the transition
      phase. For all 3 patients, the disease notably worsened because follow-up was
      interrupted during this period.

PMID- 21194905
TI  - [Necrotic skin lesions caused by pet rats in two teenagers].
AB  - We report 2 observations in young girls who, after exposure to domestic rats from
      the same pet shop, presented with inflammatory and necrotic skin wounds in the
      neck and face. Since lesions did not improve with antibiotic therapy, surgical
      excision of necrosis healed the wounds, with a 2nd intervention necessary in 1
      patient. All bacteriological investigations appeared to be negative; finally,
      electron microscopy of excised subepidermal tissue and PCR characterization
      provided the diagnosis of cowpox virus (CPXV) infection. CPXV is part of the
      Orthopox virus genus, like variola virus, and is generally transmitted to humans
      by infected cats or rodents. CPXV infection should be kept in mind when macular,
      vesicular, or necrotic cutaneous wounds do not improve with antibiotics.

PMID- 21194906
TI  - [Deadly nightshade (Atropa belladonna) intoxication in a 2-year-old child].
AB  - Plant intoxications account for 5% of all intoxication cases according to French
      anti-poison centers. We report an uncommon case of intoxication with deadly
      nightshade (Atropa belladonna) in a 2-year-old child. The child presented at the
      ER with an atropinic syndrome, both central and peripheral, after ingestion of
      wild berries a few hours before. The fruit and leaves brought in by the mother
      allowed the anti-poison center to identify belladonna, in agreement with clinical
      findings. The child was kept in the intensive care unit for 48 h and progression
      was favorable with symptomatic treatment.

PMID- 21194907
TI  - [Medial cleft lip: one diagnosis masking another].
AB  - Median cleft lip and palate are one of the facial manifestations of
      holoprosencephaly, a brain malformation resulting from a defect in the
      development of the prosencephalon, the embryonic precursor of the forebrain. It
      can occur in isolation or as part of a broader pattern of malformation in many
      different syndromes. The diagnosis of holoprosencephaly requires a complete
      malformative assessment. CASE REPORT:  FIRST CASE: a newborn baby seen at birth
      for a median cleft lip associated with a complex craniofacial malformation. The
      search for malformations revealed the absence of the median cerebral structure
      and trisomy 13. The baby died at 48 h. SECOND CASE: A 28-day-old newborn baby
      consulting for a median cleft lip and palate. The brain ultrasounds showed no
      anomalies of the median cerebral structure. The malformative assessment revealed
      no other malformation. DISCUSSION: Holoprosencephaly is a complex developmental
      brain malformation. From the advances in neuroimaging and genetics, our
      understanding of the etiology and pathogenesis of this condition has advanced
      dramatically. This advance should lead to improved management of common medical
      complications and more optimal family counseling. Surgical treatment is the
      preferred therapy for viable malformations.

PMID- 21194908
TI  - Early metabolic response evaluation after stereotactic radiotherapy for lung
      cancer: pilot experience with 18F-fluorodeoxyglucose positron emission tomography
      computed tomography.
AB  - The early response of lung tumours to stereotactic radiotherapy was prospectively
      evaluated with 18F-fluorodeoxyglucose positron emission tomography-computed
      tomography. Three months after treatment, the maximum standardised uptake value
      and the tumour diameter fell by 64 and 30%, respectively. This imaging strategy
      therefore remains under ongoing evaluation with the aim of identifying predictive
      and prognostic factors.

PMID- 21194909
TI  - Prognosis by C-reactive protein and matrix metalloproteinase-9 levels in stable
      coronary heart disease during 15 years of follow-up.
AB  - BACKGROUND AND AIM: Elevated CRP and matrix metalloproteinase-9 associate with
      increased risk of cardiovascular events, possibly because these plasma proteins
      mark vulnerable atherosclerotic plaques. We tested the hypothesis that levels of
      C-reactive protein (CRP) and matrix metalloproteinase-9 associate with prognosis
      in patients with stable coronary heart disease. METHODS AND RESULTS: We measured
      baseline plasma CRP and matrix metalloproteinase-9 in 1090 patients with stable
      coronary heart disease and as the primary composite endpoint detected incident
      unstable angina, myocardial infarction and any death during 15 years of follow
      up. CRP above versus below the median of 3.0 mg/L was associated with an
      increased cumulative incidence of unstable angina, myocardial infarction and any
      death combined (log-rank p < 0.0001). CRP above versus below the median had a
      corresponding hazard ratio of 1.5(95% CI, 1.3-1.8) after age adjustment, of
      1.4(1.2-1.6) after multifactorial adjustment, and of 1.4(1.2-1.6) after
      multifactorial adjustment including degree of coronary disease. In contrast,
      matrix metalloproteinase-9 above versus below the median was not associated with
      risk of unstable angina, myocardial infarction and death. CONCLUSIONS: Elevated
      CRP, but not elevated matrix metalloproteinase-9, associates with increased risk
      of unstable angina, myocardial infarction and death in patients with stable
      coronary heart disease.

PMID- 21194910
TI  - The effect of vitamin D replacement on markers of vascular health in stroke
      patients - a randomised controlled trial.
AB  - BACKGROUND AND AIMS: Low vitamin D levels are associated with increased incidence
      of future cardiovascular events and are common in stroke patients. We tested
      whether vitamin D supplementation could reduce blood pressure and improve markers
      of vascular health in patients who had previously suffered a stroke. METHODS AND
      RESULTS: Randomised, placebo-controlled, double-blind trial. Community-dwelling
      patients with a history of stroke and baseline 25-hydroxyvitamin D levels <75
      nmol/L received 100,000 units of oral vitamin D2 or placebo at baseline. Office
      and 24 h blood pressure, endothelial function measured by flow-mediated
      dilatation of the brachial artery, cholesterol, oxidised low density lipoprotein,
      B-type natriuretic peptide and heart rate turbulence were measured at baseline, 8
      weeks and 16 weeks. 58 patients were randomised. Mean age was 67 years, mean
      baseline blood pressure 128/72 mmHg, mean baseline 25-hydroxyvitamin D level was
      38 nmol/L. Serum 25-hydroxyvitamin D levels were higher in the intervention group
      at 8 weeks compared to placebo (54 vs 42 nmol/L, P = 0.002) and remained higher
      at 16 weeks. Office systolic and diastolic blood pressure showed no significant
      change between groups at 8 weeks (systolic 126.1 vs 131.3 mmHg; adjusted P =
      0.97); (diastolic 73.1 vs 74.9 mmHg, adjusted P = 0.15). Flow mediated dilatation
      was significantly higher in the intervention group at 8 weeks (6.9% vs 3.7%,
      adjusted P = 0.007) but was not significantly different at 16 weeks. CONCLUSIONS:
      High dose oral vitamin D supplementation did not improve blood pressure but
      produced short-term improvement in endothelial function in stroke patients with
      well-controlled baseline blood pressure. CLINICAL TRIALS REGISTRATION:
      ISRCTN28737567.

PMID- 21194911
TI  - Folate, vitamin B12 and total homocysteine levels in Arab adolescent subjects:
      reference ranges and potential determinants.
AB  - BACKGROUND & AIMS: Elevated circulating fasting total homocysteine (tHcy)
      concentration is associated with an increased risk of occlusive vascular disease
      in adults. Important determinants of tHcy levels are folate, vitamin B(12) and
      vitamin B(6). This study aimed to investigate age, gender, and body mass as
      determinants of folate, vitamin B(12) and tHcy levels in Arab older children and
      adolescents and to propose population, gender and age-specific reference ranges
      for these biomarkers. METHODS & RESULTS: 774 (316 boys, 458 girls) healthy 10-19
      yr olds attending secondary schools in Kuwait were assessed for anthropometry and
      fasting blood levels of Hcy, folate and vitamin B(12). The mean (95% CI) serum
      levels of tHcy, folate and vitamin B(12) were respectively 6.57 MUmol/L (6.42
      6.73), 16.0 ng/ml (15.6-16.3) and 354.3 pg/ml (343.0-365.7). Boys had
      significantly higher tHcy and folate concentrations than the girls, although
      vitamin B(12) levels were greater in the latter. Folate and vitamin B(12) levels
      decreased significantly with age, while correspondingly, tHcy levels increased,
      with mean values (MUmol/L) for boys (6.71; 8.25) and girls (5.36; 6.67) aged 10
      14 yr and 14-19 yr respectively. Bivariate and multivariate analyses with
      adjustment for confounders such as age, gender, need for dietary control and
      socio-demographic variables indicated that the independent determinants of levels
      of tHcy were age, gender and body mass. CONCLUSION: There is an age-related
      increase in tHcy in adolescents reflecting decreased levels of folate and vitamin
      B(12), with the suggestion that age-related reference ranges for these biomarkers
      be used. These observations may have implications for prevention of future
      atherogenic disease.

PMID- 21194912
TI  - Statin use after first myocardial infarction in UK men and women from 1997 to
      2006: Who started and who continued treatment?
AB  - BACKGROUND AND AIMS: To examine trends in initiation and continuation of statin
      treatment after myocardial infarction (MI) and their determinants, during a
      period of increasing usage. METHODS AND RESULTS: 9367 patients aged 30-84 with a
      first Myocardial Infarction (MI) in 1997-2006 were identified in DIN-LINK, an
      anonymised, UK primary care database. We assessed statin initiation (prescription
      within 6 months of MI) and continued therapy (% covered by a prescription on a
      given day of those prescribed a statin within 6 months). The influences of co
      morbidities and socio-economic deprivation (Index of Multiple Deprivation) were
      examined. Statin initiation increased from 37% for MIs in 1997 to 92% in 2006.
      Continuation at 1 year remained stable over successive cohorts at approximately
      80%, settling to about 76% in patients with 5-10 years follow up. Younger age,
      affluence, revascularisation in 6 months after MI, and absence of congestive
      heart failure, predicted higher initiation and continuation; a diagnosis of
      hypertension or diabetes predicted higher initiation, while smoking was
      associated with poorer continuation. Men had higher initiation and continued
      therapy, but these effects were largely explained by their younger age. Type of
      statin initially prescribed did not influence continued usage. CONCLUSION: Statin
      use after MI increased markedly between 1997 and 2006, whilst continued therapy
      remained high and stable. Importantly, first choice of statin had no effect on
      continuation. Whilst the high current levels of initiation may have reached a
      ceiling, increasing continuation rates among smokers, older patients and those
      from lower socio-economic groups, should remain a priority.

PMID- 21194913
TI  - Does a Mediterranean diet reduce the mortality risk associated with diabetes:
      evidence from the Melbourne Collaborative Cohort Study.
AB  - BACKGROUND AND AIMS: Diabetes is a risk factor for cardiovascular disease (CVD),
      yet southern European migrants to Australia with high rates of type 2 diabetes
      have relatively low CVD mortality. Our aim was to determine whether a
      Mediterranean style diet could reduce mortality in people with diabetes. METHODS
      AND RESULTS: Participants included 16,610 males and 23,860 females from the
      Melbourne Collaborative Cohort Study; 25% were born in Greece or Italy, and 2150
      had previously been diagnosed with diabetes or had elevated blood glucose at
      baseline (1990-94). Data on demographic, behavioral and physical risk factors
      were also collected. A personal Mediterranean Diet Score (MDS) was calculated
      using data from a validated 121-item food frequency questionnaire. Total and CVD
      mortality data were available up to 2003. Diabetes (new and known) at baseline,
      was associated with total mortality (men HR 1.43, 95%CI 1.26-1.62; women HR 1.86
      95%CI 1.58-2.18), and CVD mortality (men HR 1.53, 95%CI 1.21-1.94; women HR 2.10
      95%CI 1.48-2.97) in multivariate models. There was no evidence that glucose
      tolerance modified the associations between MDS and total or CVD mortality (p
      interaction all > 0.16). The HRs for total mortality per unit of MDS were 0.96
      (95% CI 0.93-0.99) in men and 0.94 (95% CI 0.92-0.97) in women. The HRs for CVD
      mortality per unit of MDS were 0.94 (95% CI 0.89-0.99) in men and 0.94 (95% CI
      0.87-1.01) in women. CONCLUSION: Our results add to the evidence supporting the
      benefit of a Mediterranean style diet for people with type 2 diabetes.

PMID- 21194914
TI  - Methylmercury-induced changes in target organs of suckling rat pups.
AB  - Methylmercury (MeHg) is an organic form of mercury with toxic effects in multiple
      organs. The aim of the present investigation was to evaluate the in vivo effects
      of MeHg (1 and 4 mg/kg) given orally for seven consecutive days on adenosine
      deaminase (ADA), n-acetyl-beta-D-glucosaminidase (NAG) and ecto-nucleoside
      triphosphate phosphohydrolase (NTPDase) activities, and on lipid peroxidation in
      hippocampus, cerebral cortex, kidney and liver of suckling rat pups. The results
      showed that NAG activity and lipid peroxidation levels increased in the kidney in
      both treatments, whereas urinary NAG activity increased only in the 1 mg/kg
      treatment. Despite the fact that the lipid peroxidation increased in both
      cerebral cortex and hippocampus, the latter appeared to be more vulnerable to
      MeHg exposure as it also had an increase in ADA activity. Thus, although dietary
      MeHg modified renal cell function, it did not alter histological features in
      suckling rat pups. The results of our investigation are of significant importance
      because they demonstrated responses to exposition to low doses of MeHg in target
      organs during the development of the rat. Especially the kidney was affected by
      the oral exposure to MeHg, suggesting the vulnerability of this organ at this
      stage of development. Moreover, the urinary NAG may provide important data that
      could serve as basis for risk assessment purposes following MeHg exposure.

PMID- 21194915
TI  - Cytokine crosstalk for thymic medulla formation.
AB  - The medullary microenvironment of the thymus plays a crucial role in the
      establishment of self-tolerance through the deletion of self-reactive thymocytes
      and the generation of regulatory T cells. Crosstalk or bidirectional signal
      exchanges between developing thymocytes and medullary thymic epithelial cells
      (mTECs) contribute to the formation of the thymic medulla. Recent studies have
      identified the molecules that mediate thymic crosstalk. Tumor necrosis factor
      superfamily cytokines, including RANKL, CD40L, and lymphotoxin, produced by
      positively selected thymocytes and lymphoid tissue inducer cells promote the
      proliferation and differentiation of mTECs. In return, CCR7 ligand chemokines
      produced by mTECs facilitate the migration of positively selected thymocytes to
      the medulla. The cytokine crosstalk between developing thymocytes and mTECs
      nurtures the formation of the thymic medulla and thereby regulates the
      establishment of self-tolerance.

PMID- 21194916
TI  - Indicators for ventilator use in Duchenne muscular dystrophy.
AB  - BACKGROUND: Noninvasive mechanical ventilation is being used up to continuously
      by patients with Duchenne muscular dystrophy (DMD). Invasive and noninvasive
      tests are used to assess ventilatory function but there are few reports relating
      them to extent of ventilator dependence for which simple and cost effective
      parameters are needed. OBJECTIVE: To investigate the relative efficacy of
      noninvasive lung function parameters for determining extent of need for
      ventilator use. MATERIALS AND METHODS: 83 DMD patients were divided into three
      groups: no ventilator use (asymptomatic) (n = 26) [Group 1], nocturnal ventilator
      use (symptomatic) (n = 20) [Group 2], and full-time ventilator dependence (n =
      37) [Group 3]. Tidal volume (TV), vital capacity (VC), respiratory rate (RR),
      inspiratory time (Ti), respiratory cycle time (Ttot), rapid shallow breathing
      index (RSBI [RR/TV]), breathing intolerance index (BITI), ventilator requirement
      index (VRI) and a new parameter RR/VC were monitored and compared. Data were
      analyzed with receiver-operating-characteristic curves (ROC) and the area under
      the curve (AUC) was calculated. RESULTS: In group 2 and 3, patients used NIV for
      3.3 +/- 2.1 and 11.2 +/- 4.7 years, respectively. By ROC comparison, RR/VC (RR/VC
      >= 0.024 [AUC, 0.921] and >=0.071 [AUC, 0.935]), RR/TV (RR/TV >= 0.024 [AUC,
      0.905] and >=0.153 [AUC, 0.905]), and VC (VC <= 770 ml [AUC, 0.896] and <=370 ml
      [AUC, 0.898]) represented to introduce nocturnal and continuous ventilator use,
      respectively. TV/VC, BITI, and VRI were either less sensitive or less specific.
      CONCLUSIONS: Lung function parameters including RR/VC, RR/TV, and VC are useful
      and inexpensive in predicting the extent of need for ventilator use. Overall,
      RR/VC is the most appropriate predictor for determining extent of need for
      ventilator use.

PMID- 21194917
TI  - Online sorting of recovered wood waste by automated XRF-technology: part II.
      Sorting efficiencies.
AB  - Sorting of waste wood is an important process practiced at recycling facilities
      in order to detect and divert contaminants from recycled wood products.
      Contaminants of concern include arsenic, chromium and copper found in chemically
      preserved wood. The objective of this research was to evaluate the sorting
      efficiencies of both treated and untreated parts of the wood waste stream, and
      metal (As, Cr and Cu) mass recoveries by the use of automated X-ray fluorescence
      (XRF) systems. A full-scale system was used for experimentation. This unit
      consisted of an XRF-detection chamber mounted on the top of a conveyor and a
      pneumatic slide-way diverter which sorted wood into presumed treated and presumed
      untreated piles. A randomized block design was used to evaluate the operational
      conveyance parameters of the system, including wood feed rate and conveyor belt
      speed. Results indicated that online sorting efficiencies of waste wood by XRF
      technology were high based on number and weight of pieces (70-87% and 75-92% for
      treated wood and 66-97% and 68-96% for untreated wood, respectively). These
      sorting efficiencies achieved mass recovery for metals of 81-99% for As, 75-95%
      for Cu and 82-99% of Cr. The incorrect sorting of wood was attributed almost
      equally to deficiencies in the detection and conveyance/diversion systems. Even
      with its deficiencies, the system was capable of producing a recyclable portion
      that met residential soil quality levels established for Florida, for an infeed
      that contained 5% of treated wood.

PMID- 21194918
TI  - A serotonin-sensitive sensor for investigation of taste cell-to-cell
      communication.
AB  - Taste receptor cells are the taste sensation elements for sour, salty, sweet,
      bitter and umami sensations. It was demonstrated that there are cell-to-cell
      communications between type II (sour) and type III (sweet, bitter and umami)
      taste cells. Serotonin (5-HT) is released from type III cells, which is the only
      type of taste cells that has synaptic process with sensory afferent fibers. Then,
      taste information is transmitted via fibers to the brain. During this process, 5
      HT plays important roles in taste information transmission. In order to explore a
      sensor to detect 5-HT released from taste cell or taste cell networks, we develop
      a 5-HT sensitive sensor based on LAPS chip. This sensor performs with a detection
      limit of 3.3 * 10(-13)M and a sensitivity of 19.1 mV per concentration decade.
      Upon the stimuli of sour and mix (bitter, sweet and umami) tastants, 5-HT
      released from taste cells could be detected flexibly, benefit from the
      addressability of LAPS chip. The experimental results show that the local
      concentration of 5-HT is around several nM, which is consistent with those from
      other methods. In addition, immunofluorescent imaging technique is utilized to
      confirm the functional existence of both type II and III cells in a cluster of
      isolated taste cells. Different types of taste cells are labeled with
      corresponding specific antibody. This 5-HT sensitive LAPS chip provides a
      potential and promising way to detect 5-HT and to investigate the taste coding
      and information communication mechanisms.

PMID- 21194919
TI  - Simultaneous monitoring of excitatory postsynaptic potentials and extracellular L
      glutamate in mouse hippocampal slices.
AB  - Simultaneous monitoring of amperometric currents at a glass capillary sensor
      based on recombinant GluOx and field excitatory postsynaptic potentials (fEPSPs)
      were performed in region CA1 of mouse hippocampal slices. A transient increase in
      the glutamate current relative to the basal one at control stimulation (0.052Hz)
      was evoked by stimulation at 2 Hz for 2 min. The magnitude of the glutamate
      current was dependent on the intensity (current) of a 2 Hz stimulus and reflected
      the slope of the fEPSP. The in situ calibration of the L-glutamate sensor
      revealed that the extracellular concentration of L-glutamate released by 2 Hz
      stimulation before tetanus is in the range from 0.8 to 2.2 MUM and it is enhanced
      after tetanic stimulation. The L-glutamate level at a test stimulus (0.052 Hz)
      was estimated to be 32 nM. The recombinant GluOx-based sensor exhibited weak
      responses to glutamine above 300 MUM and L-aspartic acid above 200 MUM. The
      potential use of a glass capillary sensor in combination with fEPSP measurements
      for electrophysiological study is discussed.

PMID- 21194920
TI  - Simultaneous topographic and amperometric membrane mapping using an AFM probe
      integrated biosensor.
AB  - The investigation of the plasma membrane with intercorrelated multiparameter
      techniques is a prerequisite for understanding its function. Presented here, is a
      simultaneous electrochemical and topographic study of the cell membrane using a
      miniaturized amperometric enzymatic biosensor. The fabrication of this biosensor
      is also reported. The biosensor combines a scanning force microscopy (AFM) gold
      coated cantilever and an enzymatic transducer layer of peroxidases (PODs). When
      these enzymes are brought in contact with the substrate, the specific redox
      reaction produces an electric current. The intensity of this current is detected
      simultaneously with the surface imaging. For sensor characterization,
      hydroquinone-2-carboxylic acid (HQ) is selected as an intrinsic source of
      H(2)O(2). HQ has been electrochemically regenerated by the reduction of
      antraquinone-2-carboxylic acid (AQ). The biosensor reaches the steady state value
      of the current intensity in 1 +/- 0.2s.

PMID- 21194922
TI  - Stage migration after introduction of sentinel lymph node dissection in breast
      cancer treatment in Denmark: a nationwide study.
AB  - PURPOSE: To estimate the size and therapeutic consequences of stage migration
      after introduction of sentinel lymph node dissection (SLND) in breast cancer
      treatment in Denmark. PATIENTS AND METHODS: We compared the distribution of lymph
      node metastases in breast cancer patients operated in 1993-1996 and 2005-2008;
      before and after introducing SLND. The study was based on data from the national
      Danish Breast Cancer Cooperative Group (DBCG) database. RESULTS: We included
      24,051 patients in the study; 10,231 patients from the first period and 13,820
      from the second period. The proportion of patients having macrometastases was not
      significantly different in the two periods, whereas the proportion of patients
      with micrometastases increased from 5.1% to 9.0% (P<0.0001). However, this only
      resulted in an estimated change, from 7.8% to 8.8%, in the proportion of patients
      offered adjuvant systemic treatment due to positive nodal status as the only high
      risk criterion, when using today's criteria for risk-allocation. In addition, we
      found that negative hormone receptor status was associated to negative nodal
      status when adjusted for confounders (odds ratios (OR) 0.83, P<0.0001).
      CONCLUSION: Introduction of SLND in breast cancer treatment in Denmark has
      resulted in a stage migration on 4% due to identification of more
      micrometastases. However, this stage migration has only minor impact on patients
      offered adjuvant systemic treatment because nodal status today is less important
      in risk-allocation.

PMID- 21194921
TI  - A randomised, double-blinded, placebo-controlled study of acupressure wristbands
      for the prevention of nausea and vomiting during labour and delivery.
AB  - INTRODUCTION: Approximately 50% of women experience nausea or vomiting during
      labour. P6 acupoint stimulation reduces postoperative nausea and vomiting in
      early pregnancy and after chemotherapy. The aim of this randomised, double
      blinded, placebo-controlled trial was to determine whether P6 acupressure
      prevented nausea and vomiting during labour and delivery. METHODS: After ethical
      approval and informed consent, women admitted for induction of labour, or in
      spontaneous labour, were randomised to receive either acupressure bands (Pressure
      Right) (Group A) or sham placebo bands (Group P) applied to each wrist.
      Exclusions included recent nausea or vomiting. RESULTS: We consented 365 women
      and randomised 340 (170 per group). The groups had similar patient and labour
      characteristics. The incidence of nausea and/or vomiting did not significantly
      differ (Group A 53% vs. Group P 50%, P=0.58). There was no significant difference
      between groups (A vs. P, respectively) in the incidence of nausea (52% vs. 45%),
      vomiting (27% vs. 28%), rescue antiemetic treatment (27% in both), severity of
      nausea or vomiting, satisfaction with control of nausea or ratings of
      inconvenience or discomfort from the bands (10% vs. 11%). Factors significantly
      associated with emetic symptoms were smoking (OR 2.16, 95% CI 1.07-4.37), opioid
      analgesia (OR 1.95, 95% CI 1.06-3.59), history of motion-induced or postoperative
      nausea and vomiting (OR 1.85, 95% CI 1.17-2.94) and higher body mass index (OR
      1.07, 95% CI 1.01-1.12). CONCLUSION: In this study acupressure wristbands applied
      bilaterally did not reduce the incidence of nausea and vomiting during labour and
      delivery.

PMID- 21194923
TI  - Diagnostic and prognostic value of alpha internexin expression in a series of 409
      gliomas.
AB  - The neuronal intermediate filament alpha internexin (INA) is expressed in most
      gliomas with 1p19q codeletion and could represent a valuable prognostic marker in
      clinical routine. INA expression was analysed on 409 gliomas and correlated with
      histology, progression free survival (PFS), overall survival (OS), genomic
      profile assessed by CGH-array, IDH1/IDH2 mutation and p53 expression. INA was
      expressed in 59% of grade II oligodendrogliomas (n=73), 45% of grade III
      oligodendrogliomas (n=133), 15% of grade II oligoastrocytomas (n=61), 12% of
      grade III oligoastrocytomas (n=41), 23% of glioblastomas with oligodendroglial
      component (n=31), 0% of grade I astrocytomas (n=3), 0% of grade II astrocytomas
      (n=14), 6% of grade III astrocytomas (n=17) and 0% of glioblastomas (n=36). INA
      expression was detected in 85% of gliomas with complete 1p19q codeletion ('true
      1p19q signature') (n=85) versus 15% of gliomas without 1p19q codeletion (n=245),
      including 14% of gliomas with variable/partial 1p19q deletion ('false 1p19q
      signature') (n=72) (p<0.0001). INA was expressed by 43% of gliomas with IDH1
      mutation (n=197) versus 12% of gliomas without IDH1 mutation (n=156) (p<0.0001).
      In oligodendroglial gliomas (n=240), INA expression specificity for 1p19q
      codeletion was 80%, sensitivity 85%, positive predictive value 70%, and negative
      predictive value was 91%. Combining INA and p53 expressions improved INA
      predictive accuracy for 1p19q codeletion. In grade III gliomas, INA expression
      was associated with longer PFS (42.1 versus 10.2 months, p=0.0007) and longer OS
      (124.6 versus 20.6 months, p=0.0001). In conclusion, INA expression is a fast,
      cheap and reliable prognostic marker, and represents a surrogate marker for 1p19q
      complete codeletion.

PMID- 21194924
TI  - Chlamydia pneumoniae infection and lung cancer risk: a meta-analysis.
AB  - Chlamydia pneumoniae (C. pneumoniae) is a common cause of acute respiratory
      infection and has been hypothesised to cause several chronic diseases, including
      lung cancer. Numbers studies were conducted to analyse the association between C.
      pneumoniae infection and risk of lung cancer, but no clear consensus had been
      found. To assess this relationship more precisely, a meta-analysis was performed.
      The electronic databases PubMed, Embase, Web of Science and CNKI were searched;
      Data were extracted and analysed independently by two investigators. Ultimately,
      12 studies, involving 2595 lung cancer cases and 2585 controls from four
      prospective studies and eight retrospective studies were included. Overall,
      people exposed to C. pneumoniae infection had an odds ratio (OR) of 1.48 (95%
      confidence interval (CI), 1.32-1.67) for lung cancer risk, relative to those not
      exposed. C. pneumoniae infection was clearly identified as a risk factor for lung
      cancer in both prospective studies (OR, 1.16; 95% CI, 1.00-1.36) and
      retrospective studies (OR, 2.17; 95% CI, 1.79-2.63) and in both IgA >= 16 cutoff
      group (OR, 1.22; 95% CI, 1.06-1.41) and the IgA >= 64 cutoff group (OR, 2.35; 95%
      CI, 1.88-2.93). In conclusion, C. pneumoniae infection is associated with an
      increased risk for lung cancer, higher titre may be a better predictor of lung
      cancer risk.

PMID- 21194925
TI  - Protein kinase CK2alpha subunit over-expression correlates with metastatic risk
      in breast carcinomas: quantitative immunohistochemistry in tissue microarrays.
AB  - BACKGROUND: CK2alpha is a signalling molecule that participates in major events
      in solid tumour progression. The aim of this study was to evaluate the prognostic
      significance of the immunohistochemical expression of CK2alpha in breast
      carcinomas. METHODS: Quantitative measurements of immunohistochemical expression
      of 33 biomarkers using high-throughput densitometry, assessed on digitised
      microscopic tissue micro-array images were correlated with clinical outcome in
      1000 breast carcinomas using univariate and multivariate analyses. RESULTS: In
      univariate analysis, CK2alpha was a significant prognostic indicator (p<0.001).
      Moreover, a multivariable model allowed the selection of the best combination of
      the 33 biomarkers to predict patients' outcome through logistic regression. A
      nine-marker signature highly predictive of metastatic risk, associating SHARP-2,
      STAT1, eIF4E, pmapKAPk-2, pAKT, caveolin, VEGF, FGF-1 and CK2alpha permitted to
      classify well 82.32% of patients (specificity 81.59%, sensitivity 92.55%, area
      under ROC curve 0.939). Importantly, in a node negative subset of patients an
      even more (86%) clinically relevant association of eleven markers was found
      predictive of poor outcome. CONCLUSION: A strong quantitative CK2alpha
      immunohistochemical expression in breast carcinomas is individually a significant
      indicator of poor prognosis. Moreover, an immunohistochemical signature of 11
      markers including CK2alpha accurately (86%) well classifies node negative
      patients in good and poor outcome subsets. Our results suggest that CK2alpha
      evaluation together with key downstream CK2 targets might be a useful tool to
      identify patients at high risk of distant metastases and that CK2 can be
      considered as a relevant target for potential specific therapy.

PMID- 21194926
TI  - Immobilization of catalase via adsorption on poly(styrene-d-glycidylmethacrylate)
      grafted and tetraethyldiethylenetriamine ligand attached microbeads.
AB  - Fibrous poly(styrene-d-glycidylmethacrylate) (P(S-GMA)) brushes were grafted on
      poly(styrene-divinylbenzene) (P(S-DVB)) beads using surface initiated-atom
      transfer radical polymerization (SI-ATRP). Tetraethyldiethylenetriamine (TEDETA)
      ligand was incorporated on P(GMA) block. The multi-modal ligand attached beads
      were used for reversible immobilization of catalase. The influences of pH, ionic
      strength and initial catalase concentration on the immobilization capacities of
      the P(S-DVB)-g-P(S-GMA)-TEDETA beads have been investigated. Catalase adsorption
      capacity of P(S-DVB-g-P(S-GMA)-TEDETA beads was found to be 40.8 +/- 1.7 mg/g
      beads at pH 6.5 (with an initial catalase concentration 1.0mg/mL). The K(m) value
      for immobilized catalase on the P(S-DVB-g-P(S-GMA)-TEDETA beads (0.43 +/- 0.02
      mM) was found about 1.7-fold higher than that of free enzyme (0.25 +/- 0.03 mM).
      Optimum operational temperature and pH was increased upon immobilization. The
      same support was repeatedly used five times for immobilization of catalase after
      regeneration without significant loss in adsorption capacity or enzyme activity.

PMID- 21194927
TI  - Sulfur oxidation activities of pure and mixed thermophiles and sulfur speciation
      in bioleaching of chalcopyrite.
AB  - The sulfur oxidation activities of four pure thermophilic archaea Acidianus
      brierleyi (JCM 8954), Metallosphaera sedula (YN 23), Acidianus manzaensis (YN 25)
      and Sulfolobus metallicus (YN 24) and their mixture in bioleaching chalcopyrite
      were compared. Meanwhile, the relevant surface sulfur speciation of chalcopyrite
      leached with the mixed thermophilic archaea was investigated. The results showed
      that the mixed culture, with contributing significantly to the raising of
      leaching rate and accelerating the formation of leaching products, may have a
      higher sulfur oxidation activity than the pure cultures, and jarosite was the
      main passivation component hindering the dissolution of chalcopyrite, while
      elemental sulfur seemed to have no influence on the dissolution of chalcopyrite.
      In addition, the present results supported the former speculation, i.e.,
      covellite might be converted from chalcocite during the leaching experiments, and
      the elemental sulfur may partially be the derivation of covellite and chalcocite.

PMID- 21194928
TI  - Enhancement of riboflavin production with Bacillus subtilis by expression and
      site-directed mutagenesis of zwf and gnd gene from Corynebacterium glutamicum.
AB  - Zwf (code for glucose-6-phosphate dehydrogenase) and gnd (code for 6
      phosphogluconate dehydrogenase) genes from Corynebacterium glutamicum were
      firstly cloned, and then site-directed mutagenesis was successfully introduced to
      remove allosteric inhibition by intracellular metabolites. Expression of the
      mutant zwf and gnd in Bacillus subtilis RH33 resulted in significant enhancement
      of riboflavin productivity, while the specific growth rate decreased slightly and
      the specific glucose uptake rate was unchanged. Introduction of the mutant zwf
      and gnd led to approximately 18% and 22% increased riboflavin production,
      respectively. An improvement by 31% and 39% of the riboflavin production was
      obtained by co-expression of the mutated dehydrogenases in shaker flask and fed
      batch cultivation. Intracellular metabolites analysis indicated that metabolites
      detected in pentose phosphate pathway or riboflavin synthesis pathway of
      engineered strains showed higher concentration, while TCA cycle and glycolysis
      metabolites detected were lower abundance than that of parent strain.

PMID- 21194929
TI  - Expediting COD removal in microbial electrolysis cells by increasing biomass
      concentration.
AB  - Microorganisms catalyse the reaction and in this study, mainly the effect of
      different concentration of biomass on COD removal was investigated. Three sets of
      two-compartment reactors were established. The cation exchange membrane (CEM) was
      employed in each reactor and 0.5 V of electricity was supplied. Graphite rod
      employed in cathodic part and a combination of graphite rod and graphite granules
      were used in anodic chamber. The highest rate of COD removal (40 +/- 2.0 ppm/h)
      was achieved in the reactor which had initial VSS at 6130 mg/l, whereas the
      slowest rate of 23 +/- 1.2 ppm/h in the reactor started with 3365 mgVSS/l. Some
      ammonia removal was also noticed during the operation. Further understanding and
      improvement is needed to be competitive against traditional wastewater treatment
      processes.

PMID- 21194930
TI  - On hexenuronic acid (HexA) removal and mediator coupling to pulp fiber in the
      laccase/mediator treatment.
AB  - Flax soda/AQ pulps were treated with different fungal laccase-mediator
      combinations followed by physical and chemical characterization of the pulps to
      obtain a thorough understanding of the laccase/mediator effects on hexenuronic
      acid (HexA) removal and the coupling of mediator onto pulps for fiber
      functionalization. Large differences were found and the presence of lauryl
      gallate (LG) during Trametes villosa laccase (TvL) treatment (TvL+LG) resulted in
      a much larger reduction of pulp-linked HexA than the combination of p-coumaric
      acid (PCA) and Pycnoporus cinnabarinus laccase (PcL). A major portion of LG
      became attached to the pulp as revealed by an increase in the kappa number and
      further confirmed by thioacidolysis and (1)H NMR analysis of solubilized pulp
      fractions. Additional experiments with other chemical pulps and isolated pulp
      xylan and lignin revealed that HexA seems to be the sole pulp component attacked
      by TvL+LG. As a substrate for TvL, the reaction preference order is PCA>HexA>LG.

PMID- 21194931
TI  - Pretreatment of switchgrass for sugar production with the combination of sodium
      hydroxide and lime.
AB  - Sodium hydroxide (NaOH) and lime (Ca(OH)(2)) were innovatively used together in
      this study to improve the cost-effectiveness of alkaline pretreatment of
      switchgrass at ambient temperature. Based on the sugar production in enzymatic
      hydrolysis, the best pretreatment conditions were determined as: residence time
      of 6h, NaOH loading of 0.10 g/g raw biomass, NaOH addition at the beginning,
      Ca(OH)(2) loading of 0.02 g/g raw biomass, and biomass wash intensity of 100ml
      water/g raw biomass, at which the glucose and xylose yields were respectively
      59.4% and 57.3% of the theoretical yields. The sugar yield of the biomass
      pretreated using the combination of 0.10 g NaOH/g raw biomass and 0.02 g
      Ca(OH)(2)/g raw biomass was found comparable with that of the biomass pretreated
      using 0.20 g NaOH/g raw biomass at the same conditions, while the chemical
      expense was remarkably reduced due to the low cost of lime and the reduced
      loading of NaOH.

PMID- 21194932
TI  - A meta-analysis of the microbial diversity observed in anaerobic digesters.
AB  - In this study, the collective microbial diversity in anaerobic digesters was
      examined using a meta-analysis approach. All 16S rRNA gene sequences recovered
      from anaerobic digesters available in public databases were retrieved and
      subjected to phylogenetic and statistical analyses. As of May 2010, 16,519
      bacterial and 2869 archaeal sequences were found in GenBank. The bacterial
      sequences were assigned to 5926 operational taxonomic units (OTUs, based on >=
      97% sequence identity) representing 28 known bacterial phyla, with Proteobacteria
      (1590 OTUs), Firmicutes (1352 OTUs), Bacteroidetes (705 OTUs), and Chloroflexi
      (693 OTUs) being predominant. Archaeal sequences were assigned to 296 OTUs,
      primarily Methanosaeta and the uncharacterized WSA2 group. Nearly 60% of all
      sequences could not be classified to any established genus. Rarefaction analysis
      indicates that approximately 60% of bacterial and 90% of archaeal diversity in
      anaerobic digesters has been sampled. This analysis of the global bacterial and
      archaeal diversity in AD systems can guide future studies to further examine the
      microbial diversity involved in AD and development of comprehensive analytical
      tools.

PMID- 21194933
TI  - Biohydrogen and methane production by co-digestion of cassava stillage and excess
      sludge under thermophilic condition.
AB  - Thermophilic anaerobic hydrogen and methane production by co-digestion of cassava
      stillage (CS) and excess sludge (ES) was investigated in this study. The improved
      hydrogen and subsequent methane production were observed by co-digestion of CS
      with certain amount of ES in batch experiments. Compared with one phase anaerobic
      digestion, two phase anaerobic digestion offered an attractive alternative with
      more abundant biogas production and energy yield, e.g., the total energy yield in
      two phase obtained at VS(CS)/VS(ES) of 3:1 was 25% higher than the value of one
      phase. Results from continuous experiments further demonstrated that
      VS(CS)/VS(ES) of 3:1 was optimal for hydrogen production with the highest
      hydrogen yield of 74 mL/gtotal VS added, the balanced nutrient condition with C/N
      ratio of 1.5 g carbohydrate-COD/gprotein-COD or 11.9 g C/gN might be the main
      reason for such enhancement. VS(CS)/VS(ES) of 3:1 was also optimal for continuous
      methane production considering the higher methane yield of 350 mL/gtotal VS added
      and the lower propionate concentration in the effluent.

PMID- 21194934
TI  - Pretreatment of municipal waste activated sludge for volatile sulfur compounds
      control in anaerobic digestion.
AB  - The effect of combination of mechanical and chemical pretreatment of municipal
      waste activated sludge (WAS) prior to anaerobic digestion was studied using a
      laboratory scale system with an objective to decrease volatile sulfur compounds
      in biogas and digested sludge. Mechanical pretreatment was conducted using
      depressurization of WAS through a valve from a batch pretreatment reactor
      pressurized at 75 +/- 1 psi, while combined pretreatments were conducted using
      six different dosages of hydrogen peroxide (H(2)O(2)) and ferrous chloride
      (FeCl(2)) along with mechanical pretreatment. About 37-46% removal of H(2)S in
      biogas occurred for different combined pretreatment conditions. Sludge
      solubilization achieved due to the mechanical pretreatment increased total
      cumulative methane production by 8-10% after 30 days during the biochemical
      methane potential (BMP) test. The pretreatment also improved dewaterability in
      terms of time to filter (TTF), and decreased methyl mercaptan generation
      potential of the digested sludge.

PMID- 21194935
TI  - A novel saccharification method of starch using microwave irradiation with
      addition of activated carbon.
AB  - Activated carbons were investigated for their heat catalytic effects to improve
      saccharification of starch by autohydrolysis in water under microwave
      electromagnetic field, and the results were compared with graphite and carbon
      nanotubes. The activated carbons with low adsorptive capacity of maltose showed
      high saccharification rate, while those with high adsorptive capacity exhibited
      low saccharification. In addition, the former activated carbons decreased the
      saccharification temperature by 10-30 degrees C. Maltooligosaccharides produced
      in the presence of the latter activated carbons were recovered by desorption with
      50% aqueous ethanol. The results indicated that both adsorptive capacities of
      maltooligosaccharides and catalytic effects of hot spots arisen from the uneven
      surface structure of activated carbons might contribute to the improvement in
      starch saccharification.

PMID- 21194936
TI  - Discovery and optimization of a novel, selective and brain penetrant M1 positive
      allosteric modulator (PAM): the development of ML169, an MLPCN probe.
AB  - This Letter describes a chemical lead optimization campaign directed at
      VU0108370, a weak M(1) PAM hit with a novel chemical scaffold from a functional
      HTS screen within the MLPCN. An iterative parallel synthesis approach rapidly
      established SAR for this series and afforded VU0405652 (ML169), a potent,
      selective and brain penetrant M(1) PAM with an in vitro profile comparable to the
      prototypical M(1) PAM, BQCA, but with an improved brain to plasma ratio.

PMID- 21194937
TI  - Quencher-free molecular beacon: Enhancement of the signal-to-background ratio
      with graphene oxide.
AB  - We report the highly improved version of quencher-free molecular beacon (QF-MB)
      system by using graphene oxide (GO) as an external quencher. This QF-MB/GO system
      provided a higher S/B ratio (31.0) relative to that (2.2) of the same system in
      the absence of GO, while retaining a high selectivity for fully matched over
      single-base-mismatched targets.

PMID- 21194938
TI  - Antioxidant activity of a new C-glycosylflavone from the leaves of Ficus
      microcarpa.
AB  - By bioactive-guided fractionation of methanol extract of the Ficus microcarpa
      leaves, one new C-glucosylflavone, ficuflavoside (1), one new megastigmane
      glycoside, ficumegasoside (8), and twelve known compounds including flavonoids (2
      6), phenylpropanoids (7), megastigmanes (9-11) and sterol derivatives (12-14)
      were isolated. Their chemical structures were elucidated by mass, 1D, and 2D NMR
      spectroscopies. The antioxidant activities of these compounds were measured using
      the oxygen radical absorbance capacity methods. Compounds 1-6 exhibited potent
      antioxidant activities of 6.6-9.5MUM Trolox equivalents at the concentration of
      2.0MUM. The results indicated 2, 3, and 5 having meaningful reducing capacity of
      copper (I) ions concentration of 6.1-8.4MUM.

PMID- 21194939
TI  - Synthesis and biological evaluation of novel dihydro-aryl/alkylsulfanyl
      cyclohexylmethyl-oxopyrimidines (S-DACOs) as high active anti-HIV agents.
AB  - A novel dihydro-aryl/alkylsulfanyl-cyclohexylmethyl-oxopyrimidines (S-DACOs)
      combinatory library was synthesized and evaluated with C8166 cells infected by
      the HIV-1(IIIB) in vitro, using Nevirapine (NVP) and Zidovudine (AZT) as positive
      control. The anti-HIV screening results revealed that C-6-cyclohexylmethyl
      substituted pyrimidinones possessed higher selective index than its 6-arylmethyl
      counterparts. Compounds 1g, 1c, 1e and 1b showed potent anti-HIV activities with
      EC(50) values of 0.012, 0.025, 0.088 and 0.162nM, respectively.

PMID- 21194940
TI  - Synthetic analogs of daidzein, having more potent osteoblast stimulating effect.
AB  - A series of didzein derivatives were synthesized and assessed for stimulation of
      osteoblast differentiation using primary cultures of rat calvarial osteoblasts.
      Data suggested that three synthetic analogs, 1c, 3a and 3c were several folds
      more potent than daidzein in stimulating differentiation and mineralization of
      osteoblasts. Further, these three compounds did not show any estrogen agonistic
      activity, however had mild estrogen antagonistic effect. Out of the three
      compounds, 3c was found to maximally increase the mineralization of bone marrow
      osteoprogenitor cells. Compound 3c also robustly increased the mRNA levels of
      osteogenic genes including bone morphogenetic protein-2 and osteocalcin in
      osteoblasts. Unlike daidzein, 3c did not inhibit osteoclastogenesis.
      Collectively, we demonstrate osteogenic activity of daidzein analogs at
      significantly lower concentrations than daidzein.

PMID- 21194941
TI  - Biological study of a somatostatin mimetic based on the 1-deoxynojrimycin
      scaffold.
AB  - Previously the synthesis of novel somatostatin mimetic from 1-deoxynojirimycin
      (DNJ) led to identification of a compound with affinity for human somatostatin
      receptor subtypes 4 and 5 (hSSTR4 and hSSTR5). Here we examined the properties of
      this peptidomimetic in a human umbilical vein endothelial cell (HUVEC) based
      assays. The peptidomimetic prevented capillary tube formation based on HUVECs. It
      also inhibited HUVEC proliferation by inducing G1 phase cell cycle arrest and
      apoptosis. Stress fiber assembly and cell migration in HUVECs was markedly
      suppressed by the somatostatin receptor ligand.

PMID- 21194942
TI  - Efficient synthesis of trisaccharide saponins and their tumor cell killing
      effects through oncotic necrosis.
AB  - To investigate the relationship of cytotoxicity and saponins with varied
      aglycones, based on the structure of indioside E 1, a natural derived anti-tumor
      active ingredient from Chinese medicinal plant Solanum indicum L., five novel
      saponins 2-6 bearing the same trisaccharide moiety together with 1 were
      efficiently synthesized via a transglycosylation strategy. MTT assay revealed the
      killing effects to tumor cells of the synthesized saponins are varied with the
      change of aglycones. Furthermore, time-lapse microscopy, LDH release, PI
      staining, and immunocytochemical investigations demonstrated that the cell death
      caused by neosaponin 2 was through oncotic necrosis involving plasma membrane
      perturbation and destruction of cytoskeleton.

PMID- 21194943
TI  - Chromone 3-phenylcarboxamides as potent and selective MAO-B inhibitors.
AB  - Monoamine oxidase (MAO) is an enzyme, present in mammals in two isoforms MAO-A
      and MAO-B. These isoforms have a crucial role in neurotransmitters metabolism,
      representing an attractive drug target in the therapy of neurodegenerative
      diseases (MAO-B) and depression (MAO-A). In this context, our work has been
      focused on the discovery of new chemical entities (NCEs) for MAO inhibition,
      based on the development of chromone carboxamides. Chromone derivatives with a
      carboxamide function located in position 2- and 3- of the benzo-gamma-pyrone
      core, (compounds 2-6 and 8-12) were synthesized, with moderate/good yields, by a
      one-pot condensation reaction using phosphonium salts as coupling reagents. The
      synthetic compounds were screened towards human MAO isoforms (hMAO) to evaluate
      their potency and selectivity. The chromone-3-carboxamides show high selectivity
      to hMAO-B, with compounds 9 and 12 displaying IC(50) values at nanomolar range.

PMID- 21194944
TI  - Synthesis of 3'-azido-3'-deoxythymidine (AZT)--Cinchona alkaloid conjugates via
      click chemistry: Toward novel fluorescent markers and cytostatic agents.
AB  - Novel nucleoside-Cinchona alkaloid conjugates were synthesized using 'click'
      chemistry approach based on the copper(I) catalyzed Huisgen azide-alkyne
      cycloaddition. Two series of conjugates were prepared employing 3'-azido-3'
      deoxythymidine (AZT) as the azide component and the four 10,11-didehydro Cinchona
      alkaloids as well as their 9-O-propargyl ethers as the alkyne components. All
      obtained conjugates showed strong fluorescence emission and some of them
      exhibited marked cytotoxic activity in vitro.

PMID- 21194945
TI  - Aspergilones A and B, two benzylazaphilones with an unprecedented carbon skeleton
      from the gorgonian-derived fungus Aspergillus sp.
AB  - Two novel benzylazaphilone derivatives with an unprecedented carbon skeleton,
      aspergilone A (1), and its symmetrical dimer with a unique methylene bridge,
      aspergilone B (2), have been isolated from the culture broth of a marine-derived
      fungus Aspergillus sp. from a gorgonian Dichotella gemmacea. Their structures and
      relative stereochemistries of 1 and 2 were elucidated using a combination of NMR
      spectroscopy and X-ray crystallography. Compound 1 not only exhibited in vitro
      selective cytotoxicity but also showed potent antifouling activity.

PMID- 21194946
TI  - Ultrasound evaluation of fetal movements in pregnancies at risk for severe spinal
      muscular atrophy.
AB  - We studied spinal muscular atrophy (SMA) during human development to identify
      possible delays or alterations in fetal movements detectable by ultrasound. We
      evaluated 29 pregnancies at risk for severe SMA performing 2D-ultrasound around
      11-14 weeks, prior to prenatal molecular testing of the SMN1 gene. We charted the
      occurrence of generalized body movements, isolated movements of arms and legs,
      head movements, startle and hiccup. Fetuses were diagnosed as healthy (n=12),
      carriers (n=10) or affected (n=7) according to the SMN1 molecular testing results
      obtained. SMN2 copies were also tested in the seven affected fetuses, six of whom
      showed two SMN2 copies and one a unique SMN2 copy. The movements under study were
      observed in all recordings, regardless of group and the SMN2 copies. At the
      gestational age examined, we did not observe a qualitative early limitation of
      movements in fetuses with SMA, even in cases predicted to develop a severe
      neonatal form.

PMID- 21194947
TI  - Variable phenotypes are associated with PMP22 missense mutations.
AB  - Charcot-Marie-Tooth disease (CMT) is the commonest hereditary neuropathy
      encompassing a large group of clinically and genetically heterogeneous disorders.
      The commonest form of CMT, CMT1A, is usually caused by a 1.4 megabase duplication
      of chromosome 17 containing the PMP22 gene. Mutations of PMP22 are a less common
      cause of CMT. We describe clinical, electrophysiological and molecular findings
      of 10 patients carrying PMP22 missense mutations. The phenotype varied from mild
      hereditary neuropathy with liability to pressure palsies (HNPP) to severe CMT1.
      We identified six different point mutations, including two novel mutations. Three
      families were also found to harbour a Thr118Met mutation. Although PMP22 point
      mutations are not common, our findings highlight the importance of sequencing the
      PMP22 gene in patients with variable CMT phenotypes and also confirm that the
      PMP22 Thr118Met mutation is associated with a neuropathy albeit with reduced
      penetrance.

PMID- 21194948
TI  - AP-1 controls the trafficking of Notch and Sanpodo toward E-cadherin junctions in
      sensory organ precursors.
AB  - In Drosophila melanogaster, external sensory organs develop from a single sensory
      organ precursor (SOP). The SOP divides asymmetrically to generate daughter cells,
      whose fates are governed by differential Notch activation. Here we show that the
      clathrin adaptor AP-1 complex, localized at the trans Golgi network and in
      recycling endosomes, acts as a negative regulator of Notch signaling.
      Inactivation of AP-1 causes ligand-dependent activation of Notch, leading to a
      fate transformation within sensory organs. Loss of AP-1 affects neither cell
      polarity nor the unequal segregation of the cell fate determinants Numb and
      Neuralized. Instead, it causes apical accumulation of the Notch activator Sanpodo
      and stabilization of both Sanpodo and Notch at the interface between SOP daughter
      cells, where DE-cadherin is localized. Endocytosis-recycling assays reveal that
      AP-1 acts in recycling endosomes to prevent internalized Spdo from recycling
      toward adherens junctions. Because AP-1 does not prevent endocytosis and
      recycling of the Notch ligand Delta, our data indicate that the DE-cadherin
      junctional domain may act as a launching pad through which endocytosed Notch
      ligand is trafficked for signaling.

PMID- 21194949
TI  - Horizontal transfer of a large and highly toxic secondary metabolic gene cluster
      between fungi.
AB  - Genes involved in intermediary and secondary metabolism in fungi are frequently
      physically linked or clustered. For example, in Aspergillus nidulans the entire
      pathway for the production of sterigmatocystin (ST), a highly toxic secondary
      metabolite and a precursor to the aflatoxins (AF), is located in a ~54 kb, 23
      gene cluster. We discovered that a complete ST gene cluster in Podospora anserina
      was horizontally transferred from Aspergillus. Phylogenetic analysis shows that
      most Podospora cluster genes are adjacent to or nested within Aspergillus cluster
      genes, although the two genera belong to different taxonomic classes.
      Furthermore, the Podospora cluster is highly conserved in content, sequence, and
      microsynteny with the Aspergillus ST/AF clusters and its intergenic regions
      contain 14 putative binding sites for AflR, the transcription factor required for
      activation of the ST/AF biosynthetic genes. Examination of ~52,000 Podospora
      expressed sequence tags identified transcripts for 14 genes in the cluster, with
      several expressed at multiple life cycle stages. The presence of putative AflR
      binding sites and the expression evidence for several cluster genes, coupled with
      the recent independent discovery of ST production in Podospora [1], suggest that
      this HGT event probably resulted in a functional cluster. Given the abundance of
      metabolic gene clusters in fungi, our finding that one of the largest known
      metabolic gene clusters moved intact between species suggests that such transfers
      might have significantly contributed to fungal metabolic diversity. PAPERFLICK:

PMID- 21194950
TI  - Nuclear geometry and rapid mitosis ensure asymmetric episome segregation in
      yeast.
AB  - BACKGROUND: Asymmetric cell division drives the generation of differentiated
      cells and maintenance of stem cells. In budding yeast, autonomously replicating
      sequence (ARS) plasmids lacking centromere elements are asymmetrically segregated
      into the mother cell, where they are thought to contribute to cellular
      senescence. This phenomenon has been proposed to result from the active retention
      of plasmids through an interaction with nuclear pores. RESULTS: To investigate
      the mother-daughter segregation bias of plasmids, we used live-cell imaging to
      follow the behavior of extrachromosomal DNA. We show that both an excised DNA
      ring and a centromere-deficient ARS plasmid move freely in the nucleoplasm yet
      show a strong segregation bias for the mother cell. Computational modeling shows
      that the geometrical shape of the dividing yeast nucleus and length of mitosis
      severely restrict the passive diffusion of episomes into daughter nuclei.
      Predictions based on simulated nuclear division were tested with mutants that
      extend the length of mitosis. Finally, explaining how various anchors can improve
      mitotic segregation, we show that plasmid partitioning is improved by tethering
      the plasmid to segregating structures, such as the nuclear envelope and
      telomeres. CONCLUSIONS: The morphology and brevity of mitotic division in budding
      yeast impose physical constraints on the diffusion of material into the daughter,
      obviating the need for a retention mechanism to generate rejuvenated offspring.

PMID- 21194951
TI  - Nanog overcomes reprogramming barriers and induces pluripotency in minimal
      conditions.
AB  - Induced pluripotency requires the expression of defined factors and culture
      conditions that support the self-renewal of embryonic stem (ES) cells. Small
      molecule inhibition of MAP kinase (MEK) and glycogen synthase kinase 3 (GSK3)
      with LIF (2i/LIF) provides an optimal culture environment for mouse ES cells and
      promotes transition to naive pluripotency in partially reprogrammed (pre-iPS)
      cells. Here we show that 2i/LIF treatment in clonal lines of pre-iPS cells
      results in the activation of endogenous Nanog and rapid downregulation of
      retroviral Oct4 expression. Nanog enables somatic cell reprogramming in serum
      free medium supplemented with LIF, a culture condition which does not support
      induced pluripotency or the self-renewal of ES cells, and is sufficient to
      reprogram epiblast-derived stem cells to naive pluripotency in serum-free medium
      alone. Nanog also enhances reprogramming in cooperation with kinase inhibition or
      5-aza-cytidine, a small molecule inhibitor of DNA methylation. These results
      highlight the capacity of Nanog to overcome multiple barriers to reprogramming
      and reveal a synergy between Nanog and chemical inhibitors that promote
      reprogramming. We conclude that Nanog induces pluripotency in minimal conditions.
      This provides a strategy for imposing naive pluripotency in mammalian cells
      independently of species-specific culture requirements.

PMID- 21194952
TI  - Walking kinematics in individuals with patellofemoral pain syndrome: a case
      control study.
AB  - Patellofemoral pain syndrome (PFPS) development is considered to be
      multifactorial with various knee, hip and foot/ankle kinematic factors thought to
      be involved. A paucity of research evaluating kinematic factors throughout the
      lower limb kinematic chain simultaneously in individuals with PFPS was identified
      in a recent systematic review. The objective of this study was to compare
      kinematics at the knee, hip and foot/ankle in a group of individuals with PFPS to
      a group of asymptomatic controls. Twenty-six individuals with PFPS and 20
      controls aged between 18 and 35 were recruited. Between-group comparisons were
      made for magnitude and timing of peak angles, and range of motion at the forefoot
      (dorsiflexion, abduction and supination), rearfoot (dorsiflexion, internal
      rotation and eversion), knee (flexion, abduction and internal rotation) and hip
      (adduction and internal rotation) during walking. The PFPS group demonstrated
      less peak hip internal rotation (7.0 degrees  versus 11.8 degrees , p=0.024,
      p=0.024), earlier peak rearfoot eversion relative to the laboratory (30.4% versus
      35.3% of the gait cycle, p=0.010) and tibia (32.7% versus 36.5% of the gait
      cycle, p=0.030), and greater rearfoot dorsiflexion range of motion relative to
      the laboratory (72.3 degrees  versus 68.2 degrees , p=0.007). Additionally, a
      trend toward reduced gait velocity (p=0.070) was found in the PFPS group. Reduced
      peak hip internal rotation and gait velocity in individuals with PFPS may
      indicate compensation to reduce PFJ load during walking. However, earlier peak
      rearfoot eversion may be a factor related to the pathomechanical development of
      the condition.

PMID- 21194953
TI  - Computational approach to the identification of novel Aurora-A inhibitors.
AB  - Aurora kinase A has been emerging as a key therapeutic target for the design of
      anticancer drugs. For the purpose of finding biologically active and novel
      compounds and providing new ideas for drug-design, we performed virtual screening
      using commercially available databases. A three-dimensional common feature
      pharmacophore model was developed with the HipHop program provided in the
      Catalyst software package, and this model was used as a query for screening the
      databases. A recursive partitioning (RP) model was developed as a filtering
      system, which was able to classify active and inactive compounds. Eventually, a
      step-wise virtual screening procedure was conducted by applying the common
      feature pharmacophore and the RP model in succession to discover novel potent
      Aurora-A inhibitors. A total of 68 compounds were selected for testing of their
      in vitro anticancer activities against various human cancer cell lines. Based on
      the activity data, we have identified fifteen compounds that warrant further
      investigation. Several compounds have a high inhibition rate (above 80% at 10
      MUM) and a GI50 lower than 5 MUM for the cell lines DU145 and HT29. Enzyme assay
      for these compounds identified hits with micro molar activity. Compound C11 has
      the highest activity (IC50 = 5.09 MUM). The hits obtained from this screening
      scheme could be potential drug candidates after further optimization.

PMID- 21194954
TI  - Syntheses, structures and antibiotic activities of LpxC inhibitors based on the
      diacetylene scaffold.
AB  - Compounds inhibiting LpxC in the lipid A biosynthetic pathway are promising leads
      for novel antibiotics against multidrug-resistant Gram-negative pathogens. We
      report the syntheses and structural and biochemical characterizations of LpxC
      inhibitors based on a diphenyl-diacetylene (1,4-diphenyl-1,3-butadiyne) threonyl
      hydroxamate scaffold. These studies provide a molecular interpretation for the
      differential antibiotic activities of compounds with a substituted distal phenyl
      ring as well as the absolute stereochemical requirement at the C2, but not C3,
      position of the threonyl group.

PMID- 21194955
TI  - Dicationic phenyl-2,2'-bichalcophenes and analogues as antiprotozoal agents.
AB  - A series of phenyl-2,2'-bichalcophene diamidines 1a-h were synthesized from the
      corresponding dinitriles either via a direct reaction with LiN(TMS)2, followed by
      deprotection with ethanolic HCl or through the bis-O-acetoxyamidoxime followed by
      hydrogenation in acetic acid and EtOH over Pd-C. These diamidines show a wide
      range of DNA affinities as judged from their DeltaT(m) values which are
      remarkably sensitive to replacement of a furan unit with a thiophene one. These
      differences are explained in terms of the effect of subtle changes in geometry of
      the diamidines on binding efficacy. Five of the eight compounds were highly
      active (below 6 nM IC50) in vitro against Trypanosoma brucei rhodesiense (T. b.
      r.) and four gave IC50values less than 7 nM against Plasmodium falciparum (P.
      f.). Only one of the compounds was as effective as reference compounds in the T.
      b. r. mouse model for the acute phase of African trypanosomiasis.

PMID- 21194957
TI  - Design, synthesis and biological evaluation of novel L-lysine ureido derivatives
      as aminopeptidase N inhibitors.
AB  - As the exopeptidase over-expressed in the cell surface of endothelial cells,
      aminopeptidase N (APN/CD13) is an essential target for tumor angiogenesis and
      metastasis. Based on the previous work of L-lysine amide derivatives in our
      laboratory, we designed and synthesized two series of L-lysine ureido derivatives
      as APN inhibitors. Within these compounds, one compound, 5d (IC50 = 4.51 MUM),
      showed similar inhibitory effect compared with Bestatin (IC50 = 5.87 MUM).

PMID- 21194956
TI  - Intramolecular azo-bridge as a cystine disulfide bond surrogate: Somatostatin-14
      and brain natriuretic peptide (BNP) analogs.
AB  - Cystine disulfide bond is a common feature in numerous biologically active
      peptides and proteins and accordingly its replacement by various surrogates
      presents a potential route to obtain analogs with improved pharmacokinetic
      characteristics. The purpose of the present study was to assess whether an azo
      bridge can serve as such a surrogate. In view of the marked clinical significance
      of somatostatin and the brain natriuretic peptide (BNP) we choose these peptides
      as a model. Three cyclic-azo somatostatin analogs and three cyclic-azo BNP
      analogs were effectively prepared in solution through azo bond formation between
      p-amino phenylalanine and His or Tyr residues that were positioned in the peptide
      sequences in place of the native Cys residues. The peptides binding affinities to
      the sst2 and ANP-receptor (NPR-A) expressed on rat acinar pancreating carcinoma
      AR4-2J cell membranes and HeLa cells, respectively, were examined. The
      somatostatin analogs displayed good to moderate affinities to the rat sst2 in the
      nM range with best results obtained with peptide 2, that is, IC50 = 8.1 nM.
      Molecular dynamics simulations on these peptides suggests on a correlation
      between the observed binding potencies and the degree of conformational space
      overlapping with that of somatostatin. The BNP analogs exhibited binding
      affinities to the NPR-A in the nM range with best results obtained with BNP-1,
      that is, IC50 = 60 nM.

PMID- 21194958
TI  - Evidence for a biogenic, microorganismal origin of rock varnish from the Gangdese
      Belt of Tibet.
AB  - In the present study we examined material from the Ashikule Basin of Tibet.
      Chemical analyses were performed by use of energy dispersive X-ray spectroscopy
      and electron probe microanalysis to clarify whether the varnish layers that had
      developed on the surface of the rhyolite are indeed composed of varnish bodies
      and silica glaze. Electron microscopic analyses revealed that the surface of the
      varnish is covered both by filamentous hyphae bacterial and cocci-shaped forms.
      Within the varnish mineral layer in those samples two forms of bacteria-like
      microorganisms exist; cocci as tightly packed bacterial aggregates [within
      varnish bodies], and bacillus-like microorganisms [within the varnish matrix,
      that surrounds the varnish bodies]. The bacillus-like forms are embedded in a
      network of filaments that have diameters between 35 and 45 nm. These bacilli with
      the surrounding filaments are assumed to have been involved in biofilm formation
      (synthesis of extracellular polymeric substances) prior to their live burial. We
      concluded that the formation of the varnish layers was for the most part
      biogenically driven by microorganisms.

PMID- 21194959
TI  - Colonization of cashew plants by Lasiodiplodia theobromae: microscopical
      features.
AB  - Lasiodiplodia theobromae is a phytopathogenic fungus causing gummosis, a
      threatening disease for cashew plants in Brazil. In an attempt to investigate the
      ultrastructural features of the pathogen colonization and its response to
      immunofluorescence labeling, light, confocal and electron microscope studies were
      conducted on different severity scale patterns of diseased plants. Lasiodiplodia
      antisera was checked for cross reactivity against common cashew plants fungi.
      Optical microscopy analysis revealed a longitudinally sectioned hyphae located
      within the xylem vessels, showing an extensive hyphal development in the
      secondary xylem tissue. SEM images demonstrated that the fungus was found in some
      asymptomatic samples, particularly within the xylem vessels as confirmed by the
      optical images. Symptomatic sample images showed an extensive distribution of the
      fungus along the secondary xylem, within the vessels, infecting xylem parenchyma.
      A closer look in the secondary xylem parenchyma reveals a heavy and profuse
      invasion of the cells with a distinguishable cell wall disintegration and fully
      hyphae dispersal. There was no reactivity of Lasiodiplodia-antisera against
      mycelial extracts of Colletotrichum gloeosporioides, Phomopsis anardii and
      Pestalotiopsis guepinii. Following incubation of sections with the polyclonal
      antisera, the hyphae were intensely and regularly labeled. Rays, vessels and
      parenchyma cells were the preferred pathway for L. theobromae colonization.
      Artificial infection provides the information that the vascular cylinder is
      undoubtedly employed and used by the fungus for hyphae distribution.
      Immunofluorescence assay employed in situ was applied and the polyclonal antisera
      produced was able to recognize the fungus and proved to be a sensitive technique
      to detect it.

PMID- 21194961
TI  - Alveolar osseous distraction by the combined use of modified miniplates and an
      orthodontic appliance. A technical note.
AB  - An original alveolar osseous distraction method using a Hyrax orthodontic device
      connected to two miniplates modified as a skeletal orthodontic anchorage
      (BollardTM type) is reported and illustrated by three cases. In all three cases
      with alveolar bone insufficiency, the alveolar osseous distraction allowed for
      dental implant positioning and fixed dental prosthetic rehabilitation.

PMID- 21194960
TI  - Fibroscopic findings in patients following maxillary osteotomies in orthognathic
      surgery.
AB  - OBJECTIVE: To evaluate the intranasal complications in patients submitted to
      maxillary Le Fort osteotomy within the orthognathic evaluation through flexible
      fibroscope, method which is safety, reliable and minimally invasive. MATERIALS
      AND METHODS: A prospective, systematic non-randomized study is presented with a
      series of 47 patients who underwent a Le Fort I maxillary osteotomy due to
      dentofacial deformity between January 2008 and December 2008. The patients who
      were included underwent an evaluation of nasal respiratory function using a
      questionnaire designed for this objective, after which a fibroscopic examination
      was carried out. RESULTS: With regards to the results of the NOSE questionnaire,
      4/47 patients had Grade 2 nasal obstruction before the surgery. After the
      intervention, three improved to a 0-1 grade. 3/47 patients reported snoring
      during sleep without OSAS that was not modified as a result of the surgery. 2/47
      patients presented with sequelae regarding the deviation of the septum, and 1/47
      had a luxation of the anterior nasal spine that had not been recorded before the
      orthognathic surgery. The presence of synechiae was observed in 3/47 cases. A
      septal perforated mucosa was found in the IV area of the nasal septum.
      Hypertrophy of the lower turbinate was observed in 4/47 cases. CONCLUSION: The
      fibroscope procedure is minimally invasive and it does not require local
      anesthesia or sedation, and it allows the surgeon to carry out an immediate and
      exhaustive evaluation, on an outpatient basis, of possible septal and nasal
      sequelae in patients undergoing orthognathic surgery.

PMID- 21194962
TI  - A facial inflammatory myofibroblastic tumour in a 6-year-old girl: plastic
      surgery lessons from a rare case.
AB  - Inflammatory myofibroblastic tumours (IMT) are rare, challenging lesions with
      respect to differential diagnosis, biological behaviour and treatment. We
      reviewed the literature and report a unique case of a large (9 * 8 * 8 cm) IMT in
      the nasal region of a 6-year-old girl responsible for important facial
      deformation. Following surgical resection, without any craniofacial
      reconstruction, the dysmorphism regressed spontaneously with a good result at 2
      years of follow-up. To date, this is the largest IMT reported. Surprisingly,
      after simple excision of the tumour the craniofacial bones and soft tissues
      regained spontaneously their normal anatomical position only after a few months.
      The bone plasticity was likely due to the young age of patient and the
      preservation of periosteum and muscles during the surgical excision. We conclude
      that a conservative approach may be considered as alternative to reconstructive
      surgery in particular cases in young subjects.

PMID- 21194963
TI  - Pleurodesis for recurrent malignant pleural effusions: the quest for the Holy
      Grail.

PMID- 21194964
TI  - FGF21 reloaded: challenges of a rapidly growing field.
AB  - Fibroblast growth factor 21 (FGF21) is a pleiotropic hormone-like protein and a
      major metabolic regulator. However, several key aspects of FGF21 biology remain
      poorly understood. Indeed, the list of controversies in the FGF21 field spans a
      variety of topics, from basic matters such as the anatomic distribution of FGF21
      expression and the molecular composition of the FGF21 receptor, to the ultimate
      question of therapeutic relevance of FGF21-dependent pathways in humans. In this
      paper, we focus on current challenges in the field in an attempt to provide a
      balanced overview of FGF21 biology and guide future research into this exciting
      metabolic target.

PMID- 21194966
TI  - Percutaneous suture-mediated closure versus surgical arteriotomy in endovascular
      aortic aneurysm repair.
AB  - PURPOSE: To compare percutaneous suture-mediated closure (PSMC) with surgical
      closure in endovascular aortic aneurysm repair and examine the influence of
      obesity, sheath size, and vessel calcification on the effectiveness of
      percutaneous closure. MATERIALS AND METHODS: A total of 445 patients (mean age,
      75.9 +/- 7.6 years) undergoing aortic aneurysm repair from 2003 to 2010 were
      retrospectively reviewed. A total of 100 PSMC and 557 surgical closures for
      arteriotomies with sheath sizes between 12 F and 18 F were compared in terms of
      failure, complications, and operating room time. Additionally, effects of
      arterial calcification, body mass index, and sheath size on PSMC were evaluated.
      RESULTS: Eighty-five percent of PSMCs were successful. Failure was attributed to
      lack of hemostasis in 11 and difficulty in device positioning in four cases.
      Complication rate after successful PSMC (9.4%) was significantly less than
      surgery (19.4%) (P = .02).When failed PSMC cases were considered as complication,
      the complication rate was not different between the two groups (P = .4). Seroma
      occurred more after surgical closures (11.4% vs 1.2%; P = .001). Pseudoaneurysm
      occurred more after PSMC (3.5% vs 0.18%; P = .008).Average PSMC procedure time
      was less than that of surgical closure (P = .0001). PSMC success rate was 89.7%
      for < 16-F sheaths and 80.4% for >= 16-F sheaths (P = .15). PSMC success was not
      different between obese and nonobese patients (P = .22). PSMC success in
      calcified and noncalcified arteries was not different (P = .37). CONCLUSIONS:
      PSMC is an effective arterial closure method. It is faster and associated with
      less postprocedure morbidity than surgery. Appropriate technique and meticulous
      vascular exposure affect PSMC success. Obesity, vascular calcification, and
      sheath size did not change PSMC outcome in this study.

PMID- 21194965
TI  - Exposure to an organometal compound stimulates adipokine and cytokine expression
      in white adipose tissue.
AB  - OBJECTIVE: White adipose tissue (WAT) is now considered a defined tissue capable
      of interactions with other organ systems. WAT role in elevating the level of
      systemic chronic inflammation suggests that alterations in this tissue as the
      result of disease or environmental factors may influence the development and
      progression of various obesity-related pathologies. This study investigated WAT
      cell-specific responses to an organometal compound, trimethyltin (TMT), to
      determine possible contribution to induced inflammation. METHODS: Human primary
      mature adipocytes and macrophage differentiated THP-1 cells were cultured in TMT
      presence and relative toxicities and different adipokine levels were determined.
      The inflammatory response was examined in TMT presence for primary cells from
      obese ob/ob mice WAT, and after TMT injection in ob/ob mice. RESULTS: Both
      adipocytes and macrophages were resistant to cell death induced by TMT. However,
      adipocytes cultured in TMT presence showed increased expression of TNFalpha and
      IL-6, and modified leptin levels. In macrophage cultures, TMT also increased
      TNFalpha and IL-6, while MCP-1 and MIP-1alpha were decreased. In vivo, a single
      injection of TMT in ob/ob mice, elevated TNFalpha, MIP-1alpha and adiponectin in
      WAT. CONCLUSIONS: Elevation of the inflammatory related products can be induced
      by chemical exposure in adipocytes and macrophages, as well as murine WAT. These
      data suggest that numerous factors, including a systemic chemical exposure, can
      induce an inflammatory response from the WAT. Furthermore, when characterizing
      both chemical-induced toxicity and the progression of the chronic inflammation
      associated with elevated WAT content, such responses in this target tissue should
      be taken into consideration.

PMID- 21194967
TI  - Transjugular liver biopsy: comparison of sample adequacy with the use of two
      automated needle systems.
AB  - PURPOSE: To compare the adequacy of transjugular liver biopsy (TJLB) specimens
      with use of the 18-gauge Quick-Core and Flexcore needles. MATERIALS AND METHODS:
      The records of 233 patients who underwent a TJLB procedure from January 2005 to
      December 2006 were retrospectively reviewed. Tissue samples from a total of 194
      procedures were available for review; 117 TJLB procedures were performed with a
      Quick-Core needle and 77 were performed with a Flexcore needle. A single
      pathologist reviewed all the liver biopsy specimens in a blinded fashion. The
      chi(2), Fisher exact, and Student t tests were used to analyze differences
      between groups. RESULTS: The TJLB procedure was technically successful in 232 of
      233 cases (99.6%). Histologic diagnosis was possible in 96% of cases. Sample
      fragmentation rates were 24.9% with the Quick-Core needle and 14.3% with the
      Flexcore needle (P = .1). The mean numbers of complete portal tracts (CPTs) per
      submitted tissue per procedure were 10.0 +/- 4.6 for the Quick-Core needle and
      12.2 +/- 6.1 for the Flexcore needle (P = .003). The mean numbers of CPTs per
      liver sample were 2.63 +/- 1.8 for the Quick-Core needle and 3.28 +/- 3.3 for the
      Flexcore needle (P = .00004). Complications were more common in patients with
      multiple comorbidities such as renal failure and coagulopathy and those who had
      received a liver transplant. CONCLUSIONS: This study demonstrates that the 18
      gauge Flexcore TJLB system provided better liver biopsy specimens compared with
      the 18-gauge Quick-Core needle system.

PMID- 21194968
TI  - Water-soluble polyvinyl alcohol microspheres for temporary embolization:
      development and in vivo characteristics in a pig kidney model.
AB  - PURPOSE: To preliminarily examine whether solubility of water-soluble polyvinyl
      alcohol (PVA) microspheres in blood plasma changes in proportion to their degrees
      of saponification. The study also examined their feasibility as a temporary
      embolic agents in the pig renal artery. MATERIALS AND METHODS: Three types of PVA
      microspheres with the degrees of saponification of 97 mol% (S97), 98 mol% (S98),
      and 99 mol% (S99) were prepared. Seven kidneys in seven miniature pigs were
      embolized and divided into three groups so there would be at least two kidneys
      for each type of PVA. One animal in each group was euthanized immediately after
      angiography at 3 hours after embolization and the other one at 7 days after. In
      addition, one animal embolized with S99 microspheres was euthanized at 21 days
      after embolization. RESULTS: With S97 microspheres, the vascular network had
      recovered to the preembolic state by 3 hours after embolization. With S98
      microspheres, blood flow in the third-order branch had been restored in the same
      period. With S99 microspheres, the second- and lower order branches remained
      occluded until 21 days. Histopathologic specimens harvested at 3 hours revealed
      only a trace of PVA for S97 microspheres. With S98 microspheres, the vascular
      lumen was still found to be filled with PVA gel. With S99 microspheres, swollen
      microspheres densely filled the vascular lumen even on day 21. CONCLUSIONS:
      Dissolution process in vitro and the duration of arterial occlusion in vivo were
      possibly related to the degree of saponification of PVA. This result may support
      feasibility of PVA microspheres as a temporary embolic agent.

PMID- 21194969
TI  - Noninvasive treatment of deep venous thrombosis using pulsed ultrasound
      cavitation therapy (histotripsy) in a porcine model.
AB  - PURPOSE: This study evaluated histotripsy as a noninvasive, image-guided method
      of thrombolysis in a porcine model of deep vein thrombosis. Histotripsy therapy
      uses short, high-intensity, focused ultrasound pulses to cause mechanical
      breakdown of targeted soft tissue by acoustic cavitation, which is guided by real
      time ultrasound imaging. This is an in vivo feasibility study of histotripsy
      thrombolysis. METHODS AND MATERIALS: Acute thrombi were formed in the femoral
      vein of juvenile pigs weighing 30-40 kg by balloon occlusion with two catheters
      and thrombin infusion. A 10-cm-diameter 1-MHz focused transducer was used for
      therapy. An 8-MHz ultrasound imager was used to align the clot with the therapy
      focus. Therapy consisted of five cycle pulses delivered at a rate of 1 kHz and
      peak negative pressure between 14 and 19 MPa. The focus was scanned along the
      long axis of the vessel to treat the entire visible clot during ultrasound
      exposure. The targeted region identified by a hyperechoic cavitation bubble cloud
      was visualized via ultrasound during treatment. RESULTS: Thrombus breakdown was
      apparent as a decrease in echogenicity within the vessel in 10 of 12 cases and in
      7 cases improved flow through the vein as measured by color Doppler. Vessel
      histology found denudation of vascular endothelium and small pockets of
      hemorrhage in the vessel adventitia and underlying muscle and fatty tissue, but
      perforation of the vessel wall was never observed. CONCLUSIONS: The results
      indicate histotripsy has potential for development as a noninvasive treatment for
      deep vein thrombosis.

PMID- 21194970
TI  - Characterization of vascular injury responses to stent insertion in an ex-vivo
      arterial perfusion model.
AB  - PURPOSE: To develop an ex-vivo arterial perfusion model to evaluate vascular
      responses to bare metal stents (BMS) and drug-eluting stents (DES) in porcine
      carotid arteries. MATERIALS AND METHODS: Porcine carotid arteries with BMS or DES
      were cultured under hemodynamic stimuli for 24 hours and 72 hours. Vascular
      responses of arteries with stents were assessed by cellular functionality and
      gene expression and compared with a noninjured (NI) control group at each time
      point. Cellular functionality was confirmed with sequential dosing of
      norepinephrine (NE), acetylcholine (ACH), and sodium nitroprusside (SNP).
      QuantiGene (Panomics, Fremont, California) branched DNA (bDNA) assay was used to
      evaluate gene expression of endothelial cell (EC) and smooth muscle cell (SMC)
      biomarkers and compare it with responses of in-vivo arteries with stents.
      Bromodeoxyuridine (BrDU) stain was also used to detect cellular proliferation in
      the ex-vivo arteries with stents. RESULTS: EC relaxation and SMC contraction in
      response to vasoactivators indicated the arteries remained viable and functional
      for at least 72 hours in culture. SMC-dependent contractility and EC-dependent
      relaxation were lower in arteries with stents compared with NI arteries. Greater
      SMC proliferation was observed in BMS arteries compared with DES arteries.
      Cellular proliferation, EC function, and SMC marker expression at acute time
      points were similar between both models suggesting that the ex-vivo arterial
      model can provide comparative predictions of stent injury in vivo. CONCLUSIONS:
      The ex-vivo arterial perfusion model can be used as a quick and less costly (than
      current in-vivo and some in-vitro perfusion testing models) approach for
      evaluating the vascular responses to various stent design parameters (eg, strut
      thickness, strut width).

PMID- 21194971
TI  - Protein-energy nutritional status and kidney disease-specific quality of life in
      hemodialysis patients.
AB  - OBJECTIVE: Health-related quality of life (HRQOL) is an important outcome in
      dialysis care. Previous research has related protein-energy nutritional status to
      generic HRQOL domains, but it is still not clear as to how it relates to HRQOL
      domains that are unique to hemodialysis patients. Therefore, our aim was to study
      the relation between protein-energy nutritional status and kidney disease
      specific HRQOL domains in hemodialysis patients. DESIGN: This was a cross
      sectional study. SETTING: This study was performed at multiple centers. PATIENTS
      OR OTHER PARTICIPANTS: We evaluated the first 590 hemodialysis patients who had
      enrolled in the Convective Transport Study. DETERMINANTS: We measured protein
      energy nutritional status by using the Subjective Global Assessment, albumin,
      normalized nitrogen appearance, creatinine, body mass index, and cholesterol.
      MAIN OUTCOME MEASURE: HRQOL was assessed by using the Kidney Disease Quality Of
      Life-Short Form. RESULTS: In all, 83% of the cohort was found to be well
      nourished on the basis of the Subjective Global Assessment. Multiple nutritional
      parameters were positively related to the physical summary of generic HRQOL and
      to the following kidney disease-specific HRQOL scales: the effects of the kidney
      disease on daily life, the burden of the kidney disease, and overall health.
      CONCLUSIONS: This study showed that, even in predominantly well-nourished
      hemodialysis patients, protein-energy nutritional status was significantly
      related to kidney disease-specific HRQOL.

PMID- 21194972
TI  - A novel approach to the assessment of lymphocytic bronchiolitis after lung
      transplantation--transbronchial brush.
AB  - BACKGROUND: Lymphocytic bronchiolitis (LB) is the strongest risk factor for
      subsequent allograft loss due to bronchiolitis obliterative syndrome (BOS);
      however, it is poorly assessed by transbronchial biopsy (TBBx) because of
      sampling error, interpretation error and the presence of non-alloimmune airway
      inflammation. We hypothesized that flow cytometric evaluation of bronchiolar
      brushings (transbronchial brush, TBBr) may be a better approach. METHODS:
      Transbronchial brushings (2 to 3 cm from the pleural surface under radiologic
      guidance) were obtained prior to TBBx in 32 patients and analyzed by flow
      cytometry. We assessed the proportion of nucleated cells that were CD3(+)CD103(+)
      (epithelial-specific T cells). RESULTS: No adverse events occurred; 0.5% (0.27 to
      0.84) of the cells were epithelial-specific T cells and numbers increased with
      episodes of Grade A1 rejection (p < 0.01) and in patients with BOS (p = 0.02).
      Viral and invasive fungal infection were associated with marked infiltration with
      CD103(-) T cells (p < 0.01). CONCLUSION: TBBr is simple to obtain, low risk,
      quantitative, and can discriminate between infective and alloimmune LB. It may be
      a valuable addition to current lung allograft assessment.

PMID- 21194973
TI  - The effect of muscle paralysis using Botox on the healing of tendon to bone in a
      rat model.
AB  - HYPOTHESIS: Despite good clinical results after rotator cuff repair, follow-up
      studies show significant rates of failed healing. This may be because of
      excessive tension on the repaired tendon due to shoulder motion. We hypothesized
      that botulinum toxin A injections would result in improved attachment strength
      and collagen organization at the tendon-bone interface at early time points but
      may result in decreased mechanical properties at later time points because of the
      negative effects of stress deprivation. MATERIALS AND METHODS: We performed
      division and repair of the supraspinatus tendon in 132 rats: 66 underwent repair
      alone and 66 received injections of botulinum toxin into the muscle before
      repair. Rats were killed at 4, 8, and 24 weeks and were evaluated by use of
      histologic, biomechanical, and micro-computed tomography analyses. RESULTS: At 4
      and 24 weeks, there was no significant difference in load to failure between
      groups. At 8 weeks, the botulinum group had a significantly lower load to failure
      compared with controls (27.7 N vs 46.7 N, P < .01). The weight of the
      supraspinatus muscle was significantly decreased at 4 and 8 weeks in the
      botulinum group, but it recovered by 24 weeks. Micro-computed tomography analysis
      showed the botulinum group to have significantly less bone volume, total mineral
      content, and total mineral density at 8 weeks. Histologic analysis showed
      formation of a more normal tidemark and increased collagen fiber organization in
      the botulinum specimens at 4 weeks. DISCUSSION: Botulinum toxin A-treated
      specimens had increased collagen fiber organization at 4 weeks and decreased
      mechanical properties at later time points. The rapid healing of the rat rotator
      cuff likely makes it difficult to realize benefits from reduction in strain.

PMID- 21194974
TI  - Acromioclavicular dislocation after arthroscopic distal clavicle resection: a
      case report.

PMID- 21194975
TI  - The suprascapular nerve and its articular branch to the acromioclavicular joint:
      an anatomic study.
AB  - HYPOTHESIS: The suprascapular nerve and its articular branch innervate the
      acromioclavicular (AC) joint. Documenting the detailed anatomy of this
      innervation in the AC joint, including the pertinent surgical and anatomic
      relationships of the suprascapular nerve and its branches to the AC joint, will
      aid in the prevention of injury and the reduction of risk of denervation during
      shoulder surgery. MATERIALS AND METHODS: Twelve shoulders from 6 embalmed human
      cadavers were bilaterally dissected to study the course of the suprascapular
      nerve and its motor and sensory branches. RESULTS: The sensory branch runs
      superiorly to the supraspinatus muscle towards the AC joint. The average distance
      from the supraglenoid tubercle to the nerve at the coracoid base was 15 mm. The
      average distance from the coracoclavicular ligaments to the nerve at the coracoid
      base was 6 mm. The average distance from the spinoglenoid notch to the sensory
      branch at the suprascapular notch was 22 mm. The average length of the sensory
      branch was 30 mm. In half of the specimen shoulders, the suprascapular artery
      accompanied the nerve at the suprascapular notch under the transverse scapular
      ligament. DISCUSSION: The innervation of the AC joint by the suprascapular nerve
      has been described, along with pertinent distances to anatomic landmarks. The
      sensory branch of the suprascapular nerve, which passed through the scapular
      notch inferior to the transverse scapular ligament, was found in 100% of the
      study specimens. CONCLUSION: The sensory branch of the suprascapular nerve runs
      superiorly to the supraspinatus muscle towards the AC joint. The detailed
      information can be used to help decrease the risk of nerve injury during shoulder
      surgery and to aid in effectively diagnosing and treating AC joint-related
      disorders.

PMID- 21194976
TI  - Bone cement penetration pattern and primary stability testing in keeled and
      pegged glenoid components.
AB  - BACKGROUND: It has been proposed that bone mineral density has an influence on
      cement penetration in hip and knee arthroplasty. The hypotheses of this study
      were that: 1) there is a negative correlation between bone mineral density (BMD)
      and cement penetration in cemented glenoid components; and 2) that implant design
      has an influence on cement penetration into the glenoid bone. METHODS: BMD of 10
      pairs of fresh frozen scapulas was measured. Micro-computed tomography (micro-CT)
      scans in 3 different sections were analyzed after implantation of keeled and
      pegged glenoid components using a 3(rd)-generation cementing technique with a
      vacuum mixing system. Cement penetration was analyzed and correlated with BMD.
      Pull-out strength testing was performed to analyze primary stability. RESULTS:
      The overall peak BMD was 0.6 [g/cm(2)] (range, 0.33-0.98). A strong negative
      correlation between BMD and mean cement penetration was found for the peg (R(2) =
      -.83; P < .003) and for the keel group (R(2) = -.81; P < .005). Mean cement
      penetration was 78.4 mm(2) (range, 60.6-94.2) in the keel and 113.9 mm(2) (range,
      78.2-143.4) in the peg group (P < .0001). In all cases, the components were
      pulled out of the cement mantle, whereas the bone-cement interfaces remained
      intact. The mean pull-out strength was 1093N (764-1343N) for keeled and 884N (650
      1264N) for pegged components (P < .05). CONCLUSION: A modern cementing technique,
      leading to a deep bonding between bone and cement, is crucial to prevent
      loosening of glenoid components. The findings of this study might help us to
      better understand the results of follow-up studies of cemented glenoid implants.
      Our results could be helpful for the choice of implants in patients with poor
      bone quality like osteoporosis or rheumatoid arthritis.

PMID- 21194977
TI  - Symptomatic bicipitoradial bursitis: a report of two cases and review of the
      literature.

PMID- 21194978
TI  - Arthroscopic debridement for osteochondral injury of the elbow trochlea: a case
      report with a long-term follow-up.

PMID- 21194979
TI  - Regarding "Anatomy of the superior glenohumeral ligament".

PMID- 21194980
TI  - In vivo 3-dimensional analysis of scapular kinematics: comparison of dominant and
      nondominant shoulders.
AB  - BACKGROUND: Alterations in scapular motion frequently are seen in association
      with various shoulder disorders. It is common clinically to compare the
      pathological shoulder with the contralateral shoulder, in spite of arm dominance,
      to characterize the disorder. However, there have been few articles that test the
      underlying assumption that dominant and nondominant shoulders exhibit comparable
      dynamic kinematics. The purpose of this study was to compare the 3-dimensional (3
      D) scapular kinematics of dominant and nondominant shoulders during dynamic
      scapular plane elevation using 3-D-2-D (2-dimensional) registration techniques.
      MATERIALS AND METHODS: Twelve healthy males with a mean age of 32 years (range,
      27-36) were enrolled in this study. Bilateral fluoroscopic images during scapular
      plane elevation and lowering were taken, and CT-derived 3-D bone models were
      matched with the silhouette of the bones in the fluoroscopic images using 3-D-2-D
      registration techniques. Angular values of the scapula and scapulohumeral rhythm
      were compared between dominant and nondominant shoulders with statistical
      analysis. RESULTS: There was a significant difference in upward rotation angles
      between paired shoulders (P < .001), while significant differences were not found
      in the other angular values and scapulohumeral rhythm. The dominant scapulae were
      10 degrees  more downwardly rotated at rest and 4 degrees  more upwardly rotated
      during elevation compared to the nondominant scapulae. DISCUSSION/CONCLUSION:
      Scapular motion was not the same between dominant and nondominant arms in healthy
      subjects. The dominant scapula was rotated further downward at rest and reached
      greater upward rotation with abduction. These differences should be considered in
      clinical assessment of shoulder pathology.

PMID- 21194981
TI  - CD4(+) lymphoid tissue-inducer cells promote innate immunity in the gut.
AB  - Fetal CD4(+) lymphoid tissue inducer (LTi) cells play a critical role in the
      development of lymphoid tissues. Recent studies identified that LTi cells persist
      in adults and are related to a heterogeneous population of innate lymphoid cells
      that have been implicated in inflammatory responses. However, whether LTi cells
      contribute to protective immunity remains poorly defined. We demonstrate that
      after infection with Citrobacter rodentium, CD4(+) LTi cells were a dominant
      source of interleukin-22 (IL-22) early during infection. Infection-induced CD4(+)
      LTi cell responses were IL-23 dependent, and ablation of IL-23 impaired innate
      immunity. Further, depletion of CD4(+) LTi cells abrogated infection-induced
      expression of IL-22 and antimicrobial peptides, resulting in exacerbated host
      mortality. LTi cells were also found to be essential for host protective immunity
      in lymphocyte-replete hosts. Collectively these data demonstrate that adult
      CD4(+) LTi cells are a critical source of IL-22 and identify a previously
      unrecognized function for CD4(+) LTi cells in promoting innate immunity in the
      intestine.

PMID- 21194982
TI  - Deficiency of Rap1-binding protein RAPL causes lymphoproliferative disorders
      through mislocalization of p27kip1.
AB  - RAPL (an alternative spliced form of Rassf5) is a critical Ras-related protein1
      (Rap1) effector that regulates lymphocyte adhesion. Here, we have shown that in
      addition to this previously described function, RAPL also negatively controls
      lymphocyte proliferation and prevents autoimmunity and lymphoma. RAPL-deficient
      mice experienced age-related lupus-like glomerulonephritis and developed B cell
      lymphomas. RAPL-deficient lymphocytes showed hyperproliferation by enhanced S
      phase entry after antigen receptor ligation. Compared to wild-type cells, RAPL
      deficient naive lymphocytes had a 2- to 3-fold increase in Cdk2 kinase activity
      with a cytoplasmic mislocalization of the cyclin-dependent kinase inhibitor
      p27(kip1). RAPL was found to suppress the phosphorylation of p27(kip1) on serine
      10 (S10) and promoted p27(kip1) nuclear translocation. An S10A mutation in
      p27(kip1) corrected its cytoplasmic accumulation, reduced hyperproliferation in
      RAPL-deficient lymphocytes, and suppressed glomerulonephritis and development of
      B cell lymphoma. Thus, RAPL serves as a checkpoint for S phase entry to prevent
      lymphoproliferative disorders through the spatial regulation of p27(kip1).

PMID- 21194983
TI  - CD169-positive macrophages dominate antitumor immunity by crosspresenting dead
      cell-associated antigens.
AB  - The generation of tumor-directed cytotoxic T lymphocytes is considered crucial
      for the induction of antitumor immunity. To activate these CD8(+) T cells,
      antigen-presenting cells (APCs) must initially acquire tumor cell-associated
      antigens. The major source of tumor antigens is dead tumor cells, but little is
      known about how APCs in draining lymph nodes acquire and crosspresent these
      antigens. Here we show that CD169(+) macrophages phagocytose dead tumor cells
      transported via lymphatic flow and subsequently crosspresent tumor antigens to
      CD8(+) T cells. Subcutaneous immunization with irradiated tumor cells protects
      mice from syngenic tumor. However, tumor antigen-specific CD8(+) T cell
      activation and subsequent antitumor immunity are severely impaired in mice
      depleted with CD169(+) macrophages. Neither migratory dendritic cells (DCs) nor
      lymph node-resident conventional DCs are essential for the crosspresentation of
      tumor antigens. Thus, we have identified CD169(+) macrophages as lymph node
      resident APCs dominating early activation of tumor antigen-specific CD8(+) T
      cells.

PMID- 21194984
TI  - New-generation devices for highly angulated aortic necks: to bury or to praise
      Endovascular Aneurysm Repair (EVAR)?

PMID- 21194985
TI  - Early and long-term outcome after thoracic endovascular aortic repair (TEVAR) for
      acute complicated type B aortic dissection.
AB  - OBJECTIVES: The study aimed to investigate early and long-term outcome of
      thoracic endovascular aortic repair (TEVAR) for acute complicated type B
      dissection. DESIGN: This was a retrospective, single-centre, consecutive case
      series. MATERIALS AND METHODS: During the period 1999-2009, TEVAR was carried out
      in 50 patients with non-traumatic acute complicated type B dissection, and in
      another 10 patients with acute complications, including rupture, end-organ
      ischaemia and acute dilatation during the primary hospitalisation, but >14 days
      after onset of symptoms. Thus, in total, 60 patients were included; 22 with a
      DeBakey type IIIa dissection and 38 with a type IIIb; median age was 67 years.
      Early (30-day) and long-term (5-year) survival, re-intervention rate and
      complications were recorded until 1 July 2010. RESULTS: Within 30 days, two (3%)
      deaths, one (2%) paraplegia and three (5%) strokes were observed. Five-year
      survival was 87% and freedom from re-intervention at 5 years was 65%.
      CONCLUSIONS: In patients with acute complicated type B aortic dissection, TEVAR
      can be performed with excellent early and long-term survival, whereas morbidity
      and long-term durability must be further elucidated.

PMID- 21194986
TI  - Comments regarding 'fascial closure following percutaneous endovascular aneurysm
      repair'.

PMID- 21194988
TI  - Does puncture site affect the rate of nerve injuries following endovenous laser
      ablation of the small saphenous veins?
AB  - OBJECTIVES: The small saphenous vein (SSV) lies in close relationship with sural
      nerve and is at risk of damage during surgery or vein ablation procedures on this
      vein. The aim of this study was to compare the effect of puncture site for SSV
      endovenous laser ablation (EVLA) on the rate of post-operative sural nerve
      injury. DESIGN: Randomised controlled study. PATIENTS AND METHODS: Sixty patients
      with isolated SSV varicose veins (68 limbs) were randomised into two groups. All
      patients were treated with endovenous laser ablation procedures using radial
      fibres and a 1470 nm diode laser. In Group 1, SSVs were canulated from lateral
      malleolar part of the SSV. In Group 2, SSVs were canulated in the mid-calf. EVLA
      procedures were performed by using 12 W energy and 70 J cm-1 LEED (linear
      endovenous energy density). Local pain, ecchymosis, induration and paraesthesia
      in treated regions, vein diameter, treated vein length, tumescent anaesthesia
      volume, delivered energy were recorded. Follow-up visits were arranged on the 2nd
      post-operative day, 7th day, 1st, 2nd, 3rd and 6th months. RESULTS: The mean SSV
      diameters at sapheno-popliteal junction (SPJ) and calf levels were Group 1 SPJ:
      6.6 S.D. 1.2 mm, Calf: 5.1 S.D. 1.1 mm, and Group 2 SPJ: 6.8 S.D. 1.6 mm, Calf:
      4.9 S.D. 1.3 mm. Adverse events after treatment were 1 patient with induration, 3
      with ecchymosis and 6 minimal paraesthesia in Group 1 (malleolar) and 1 local
      pain, 4 minimal ecchymosis or induration and 1 paraesthesia in Group 2 (mid
      calf). In Group 1 in two patients the paraesthesia lasted 2 months and then
      resolved spontaneously. In the remaining four patients' paraesthesia resolved in
      less than 1 month without treatment. In Group 2 paraesthesia resolved
      spontaneously in two weeks. Induration, ecchymosis and local pain also resolved
      in less than 2 weeks in both groups. There was no recanalisation or reflux in the
      treated SSV of either group during the follow-up period. CONCLUSION: Treatment of
      the SSV by endovenous laser ablation using a 1470 nm laser and a radial fibre is
      safe and effective. Puncturing the vein at mid-calf level causes less post
      operative nerve injury without affecting the recanalisation rates.

PMID- 21194990
TI  - Decompression of odontogenic cystic lesions: clinical long-term study of 73
      cases.
AB  - OBJECTIVE: The aim of this study was to evaluate the effectiveness of
      decompression as the initial treatment for odontogenic cysts. STUDY DESIGN: Pre-
      and postdecompression panoramic radiographs of 57 patients treated for 73
      odontogenic cysts were reviewed for reduction parameters. Findings were evaluated
      against time of decompression and clinical and histopathologic data. RESULTS:
      Decompression reduced lesion area by a mean of 79.3%. The reaction was good in
      60% of cysts, moderate in 29%, and poor in 11%. Mean decompression time was 9.2
      +/- 5.2 months; it was 7.6 months in patients <=18 years old and 10.2 months in
      older patients (P < .0001). Mean rate of reduction was 0.14 in cysts <10 cm(2)
      and 0.10 in cysts >20 cm(2) (P = .0884); by age, values were 0.14 in patients
      <=18 years old and 0.09 in older patients (P < .05). CONCLUSIONS: Decompression
      is effective in reducing odontogenic cysts. A shorter decompression period is
      needed for young patients. For aggressive lesions, secondary definitive surgery
      is recommended.

PMID- 21194989
TI  - Oral tuberculosis in an asymptomatic pulmonary tuberculosis.
AB  - Tuberculosis (TB) has been a worldwide health problem for centuries. It most
      commonly affects the lungs, but rare oral manifestations of TB have been
      reported. The aim of this paper is to present a case of painful erythematous
      lesion of oral cavity in undiagnosed asymptomatic pulmonary tuberculosis. This
      case is unusual in that the appearance of the painful oral lesion caused the
      patient to seek professional care and was concurrent with quiescent pulmonary
      disease.

PMID- 21194991
TI  - Effects of bone morphogenetic protein 2 gene therapy on new bone formation during
      mandibular distraction osteogenesis at rapid rate in rabbits.
AB  - OBJECTIVE: We investigated the effect of recombinant human bone morphogenetic
      protein 2 (rhBMP-2) on new bone formation during rapid-rate mandibular
      distraction osteogenesis. We also explored the feasibility of using local BMP-2
      gene therapy to compensate for bad callus formation caused by a rapid distraction
      rate. STUDY DESIGN: Bone marrow mesenchymal stem cells (MSCs) from Japanese
      rabbits were transfected with adenovirus (adv)-BMP-2. The right mandibles of the
      rabbits were distracted after corticotomy. The distraction rate in group A was
      0.8 mm/d. The distraction rate in group B was 2.4 mm/d, and the distraction gap
      was injected with adv-lacZ-transfected bone marrow MSCs. The distraction rate in
      group C was 2.4 mm/d, and the distraction gap was injected with adv-BMP-2
      transfected bone marrow MSCs. New generation bone tissue in the distraction gap
      was analyzed by plain radiograph examinations, microfocus computerized tomography
      (micro-CT) examinations, and biomechanical tests at weeks 2, 4, and 8 of the
      consolidation period. RESULTS: Radiographic and micro-CT examinations showed a
      better bone quality in group C compared with group A at weeks 2 and 4 of the
      consolidation period. There was no obvious new bone formation in group B. The
      trabecular parameters (trabecular thickness, trabecular number, volumetric bone
      mineral density at tissue, and bone volume fraction) were significantly higher in
      group C than in group A at weeks 2 and 4. At week 8, no significant difference
      were detected for all parameters except trabecular number between groups A and C.
      All biomechanical stress parameters were significantly higher in group C than in
      group A at week 4, and only peak stress was significantly different at week 8.
      CONCLUSIONS: Gene therapy using rhBMP-2-modified MSCs promoted new bone formation
      during mandibular distraction osteogenesis, and effectively compensated for the
      detrimental effect of rapid distraction rate on new bone formation.

PMID- 21194992
TI  - Alveolar ridge augmentation using anodized implants coated with Escherichia coli
      derived recombinant human bone morphogenetic protein 2.
AB  - OBJECTIVE: The aim of this study was to examine the effect of Escherichia coli
      derived recombinant human bone morphogenetic protein 2 (ErhBMP-2) coated onto
      anodized implant to stimulate local bone formation, including osseointegration
      and the vertical augmentation of the alveolar ridge. STUDY DESIGN: Six young male
      adult beagle dogs were used. A crestal area was leveled on both sides of each
      test subject by removing minimal cortical bone using a round bur and without
      exposing cancellous bone. After a 2-month healing period, 3 anodized implants
      (length 8 mm, diameter 4 mm; Cowellmedi, Busan, Korea) were placed 5 mm into the
      mandibular alveolar ridge in either side. Each animal received 6 implants that
      were either coated with ErhBMP-2 (0.75 or 1.5 mg/mL concentration; Cowellmedi) or
      uncoated. This was performed using a randomized split-mouth design. A total of 36
      implants were used for this study. Twelve noncoated implants were used as
      control, and 24 BMP-coated implants were used as our experimental group, which
      was further divided into 2 groups of 12 implants each with different BMP
      concentration of 0.75 and 1.5 mg/mL. Radiologic examinations were performed
      immediately after implant placement and 4 and 8 weeks after implant placement.
      The amount of bone augmentation was evaluated by measuring the distance from the
      uppermost point of the cover screw to the marginal bone. Implant stability
      quotient (ISQ) values were measured immediately after surgery and 8 weeks after
      implant placement. Statistical analysis was performed using one-way analysis of
      variance (SPSS version 17.0) and multiple-comparison tests. Statistical
      significance was established at the 95% confidence level. RESULTS: Implants
      coated with ErhBMP-2 at 0.75 mg/mL (BMP 0.75 group) and 1.5 mg/mL (BMP 1.5 group)
      exhibited significant vertical bone formation compared with the control group
      (mean +/- SD): 0.88 +/- 0.94 versus 0.60 +/- 0.64 versus -0.52 +/- 0.64 mm,
      respectively; P < .05. There was a significant difference between the 3 groups in
      bone level change (P < .05). The BMP 0.75 and BMP 1.5 groups exhibited
      significant changes in ISQ compared with the control group: 8.17 +/- 8.31 versus
      11.50 +/- 9.02 versus 2.17 +/- 7.61, respectively; P < .05. CONCLUSION: Within
      the limits of this study, the ErhBMP-2 coating on an anodized implant may
      stimulate vertical bone augmentation, which significantly increases implant
      stability on completely healed alveolar ridges.

PMID- 21194993
TI  - Early alveolar bone regeneration in rats after topical administration of
      simvastatin.
AB  - OBJECTIVES: The aim of this study was to ultrastructurally examine the influence
      of simvastatin on bone healing in surgically created defects in rat mandibles.
      STUDY DESIGN: Bone defects 0.8 mm in diameter were created in the buccal aspect
      of first mandibular molar roots and filled with 2.5% simvastatin gel, while the
      controls were allowed to heal spontaneously. The rats were humanely killed 7, 9,
      11, or 14 days postoperatively, and the specimens were processed for scanning and
      transmission electron microscopy, as well as for colloidal gold immunolabeling of
      osteopontin. RESULTS: The regenerated alveolar bone in the simvastatin-treated
      defects presented smaller marrow spaces, and the collagen fibrils were regularly
      packed exhibiting a lamellar bone aspect. Osteopontin was present through the
      bone matrix during the wound healing and alveolar bone regeneration. CONCLUSION:
      The present study provides evidence that a single topical application of 2.5%
      simvastatin gel improves the quality of the new bone and decreases bone
      resorption.

PMID- 21194994
TI  - A study of the prevalence of methicillin-resistant Staphylococcus aureus in pigs
      and in personnel involved in the pig industry in Ireland.
AB  - To evaluate the prevalence of methicillin-resistant Staphylococcus aureus (MRSA)
      in the pig population in Ireland, nasal swabbing was employed in three abattoirs
      to screen 440 pigs from 41 geographically distributed farms. One hundred
      individuals involved in the pig industry were also nasally screened. No MRSA
      isolates were recovered from the pigs and only two of the humans tested were
      identified as MRSA carriers. Importantly, MRSA was not obtained from pig
      producers, veterinarians or abattoir employees, but was isolated from individuals
      working in the wider pig industry. Multi-locus sequence typing revealed that
      these isolates belonged to sequence types (ST) ST22 and ST1307; the latter is a
      previously unreported single locus variant of ST5. Five dust samples from each of
      the three slaughterhouses were culture-negative for MRSA. These results indicate
      that porcine colonisation by MRSA, and in particular the animal-related strain
      MRSA-ST398, was not common in Ireland during the period of study.

PMID- 21194995
TI  - Effect of middle ear effusion on the brain-stem auditory evoked response of
      Cavalier King Charles Spaniels.
AB  - Brain-stem auditory evoked responses (BAER) were assessed in 23 Cavalier King
      Charles Spaniels with and without middle ear effusion at sound intensities
      ranging from 10 to 100 dB nHL. Significant differences were found between the
      median BAER threshold for ears where effusions were present (60 dB nHL), compared
      to those without (30 dB nHL) (P=0.001). The slopes of latency-intensity functions
      from both groups did not differ, but the y-axis intercept when the x value was
      zero was greater in dogs with effusions (P=0.009), consistent with conductive
      hearing loss. Analysis of latency-intensity functions suggested the degree of
      hearing loss due to middle ear effusion was 21 dB (95% confidence between 10 and
      33 dB). Waves I-V inter-wave latency at 90 dB nHL was not significantly different
      between the two groups. These findings demonstrate that middle ear effusion is
      associated with a conductive hearing loss of 10-33 dB in affected dogs despite
      the fact that all animals studied were considered to have normal hearing by their
      owners.

PMID- 21194996
TI  - Validation of a direct time-resolved fluoroimmunoassay for progesterone in milk
      from dairy and beef cows.
AB  - The aim of this study was to validate a direct time-resolved fluoroimmunoassay
      (TR-FIA) for quantifying progesterone concentrations in milk during the bovine
      oestrous cycle. Holstein-Friesian and suckled and non-suckled Japanese Black cows
      were used to demonstrate the relationship between milk and plasma progesterone
      concentrations and to monitor progesterone profiles in milk and plasma during the
      oestrous cycle. The minimum detection level of the assay was 1.53ng/mL.
      Progesterone concentrations in milk and plasma changed in a similar manner
      throughout the oestrous cycle in dairy and beef cows, and milk and plasma
      progesterone profiles were significantly correlated (P<0.001). The study
      confirmed that a direct TR-FIA can be used to monitor the oestrous cycle in
      cattle and to quantify progesterone concentrations in whole milk.

PMID- 21194997
TI  - Self-reported sleep duration associated with distraction analgesia, hyperemia,
      and secondary hyperalgesia in the heat-capsaicin nociceptive model.
AB  - Although sleep deprivation is known to heighten pain sensitivity, the mechanisms
      by which sleep modifies nociception are largely unknown. Few studies of sleep
      pain interactions have utilized quantitative sensory testing models that
      implicate specific underlying physiologic mechanisms. One possibility, which is
      beginning to receive attention, is that differences in sleep may alter the
      analgesic effects of distraction. We utilized the heat-capsaicin nociceptive
      model to examine whether self-reported habitual sleep duration is associated with
      distraction analgesia, the degree of secondary hyperalgesia and skin flare,
      markers implicating both central and peripheral processes that heighten pain.
      Twenty-eight healthy participants completed three experimental sessions in a
      randomized within subjects design. In the pain only condition, pain was induced
      for approximately 70-min via application of heat and capsaicin to the dorsum of
      the non-dominant hand. Verbal pain ratings were obtained at regular intervals. In
      the distraction condition, identical procedures were followed, but during heat
      capsaicin pain, subjects played a series of video games. The third session
      involved assessing performance on the video games (no capsaicin). Participants
      indicated their normal self-reported habitual sleep duration over the past month.
      Individuals who slept less than 6.5 h/night in the month prior to the study
      experienced significantly less behavioral analgesia, increased skin flare and
      augmented secondary hyperalgesia. These findings suggest that reduced sleep time
      is associated with diminished analgesic benefits from distraction and/or
      individuals obtaining less sleep have a reduced ability to disengage from pain
      related sensations. The secondary hyperalgesia finding may implicate central
      involvement, whereas enhanced skin flare response suggests that sleep duration
      may also impact peripheral inflammatory mechanisms.

PMID- 21194998
TI  - Does minimal access major surgery in the newborn hurt less? An evaluation of
      cumulative opioid doses.
AB  - BACKGROUND: Minimal access surgery (MAS) in adults is associated with less
      postoperative pain in comparison to conventional 'open' surgery. It is not known
      whether this holds true for neonates as well. Less pain would imply that opioid
      consumption can be reduced, which has a beneficial effect on morbidity. AIM: To
      evaluate potential differences in' opioid consumption between neonates undergoing
      thoracoscopic minimal access surgery or conventional surgery of esophageal
      atresia (EA) and congenital diaphragmatic hernia (CDH). METHODS: In this
      retrospective cohort study we included two controls for each MAS patient, matched
      on diagnosis, sex and age at surgery. Opioid dose titration was based on
      validated pain scores (VAS and COMFORT behaviour), applied by protocol.
      Cumulative opioid doses at 12, 24, 48 h and 7 days postoperatively were compared
      between groups with the Mann-Whitney test. RESULTS: The study group consisted of
      24 MAS patients (14 EA; 10 CDH). These were matched to 48 control patients (28
      EA; 20 CDH). At none of the time points cumulative opioid (median in mg/kg (IQR))
      doses significantly differed between MAS patients and controls, both with CDH and
      EA. For example at 24 h postoperative for CDH patients cumulative opioid doses
      were [0.84(0.61-1.83) MAS vs. 1.06(0.60-1.36) p=1.0] controls, For EA patients at
      24 h the cumulative opioid doses were [0.48(0.30-0.75) MAS vs. 0.49(0.35-0.79)
      p=0.83] controls. This held true for the postoperative pain scores as well.
      CONCLUSIONS: Minimal access surgery for the repair of esophageal atresia or
      congenital diaphragmatic hernia is not associated with less cumulative opioid
      doses.

PMID- 21194999
TI  - Relaxed complex scheme suggests novel inhibitors for the lyase activity of DNA
      polymerase beta.
AB  - DNA polymerase beta (pol beta), the error-prone polymerase of base excision
      repair, plays a significant role in chemotherapeutic agent resistance. Its over
      expression reduces the efficacy of anticancer drug therapies including ionizing
      radiation, bleomycin, monofunctional alkylating agents and cisplatin. Small-scale
      studies on different types of cancer showed that pol beta is mutated in
      approximately 30% of tumors. These mutations further lower pol beta fidelity in
      DNA synthesis exposing the genome to serious mutations. These findings suggested
      pol beta as a promising therapeutic target for cancer treatment. More than 60 pol
      beta-inhibitors have been identified so far, however, most of them are either not
      potent or specific enough to become a drug. Here, we applied the relaxed complex
      scheme virtual screening (RCSVS) to allow for the full receptor flexibility in
      filtering the NCI diversity set, DrugBank compounds and a library of ~ 9000
      fragmental compounds for novel pol beta inhibitors. In this procedure we screened
      the set of ~ 12,500 compounds against an ensemble of 11 dominant-receptor
      structures representing the essential backbone dynamics of the 8 kDa domain of
      pol beta. Our results predicted new compounds that can bind with higher affinity
      to the lyase active site compared to pamoic acid (PA), a well-known inhibitor of
      DNA pol beta.

PMID- 21195001
TI  - Fluoroquinolones are associated with delayed treatment and resistance in
      tuberculosis: a systematic review and meta-analysis.
AB  - BACKGROUND: Current guidelines for treating community-acquired pneumonia
      recommend the use of fluoroquinolones for high-risk patients. Previous studies
      have reported controversial results as to whether fluoroquinolones are associated
      with delayed diagnosis and treatment of pulmonary tuberculosis (TB) and the
      development of fluoroquinolone-resistant Mycobacterium tuberculosis. We performed
      a systematic review and meta-analysis to clarify these issues. METHODS: The
      following databases were searched through September 30, 2010: PubMed, EMBASE,
      CINAHL, Cochrane Library, Web of Science, BIOSIS Previews, and the ACP Journal
      Club. We considered studies that addressed the issues of delay in diagnosis and
      treatment of TB and the development of resistance. RESULTS: Nine eligible studies
      (four for delays and five for resistance issues) were included in the meta
      analysis from the 770 articles originally identified in the database search. The
      mean duration of delayed diagnosis and treatment of pulmonary TB in the
      fluoroquinolone prescription group was 19.03 days, significantly longer than that
      in the non-fluoroquinolone group (95% confidence interval (CI) 10.87 to 27.18,
      p<0.001). The pooled odds ratio of developing a fluoroquinolone-resistant M.
      tuberculosis strain was 2.70 (95% CI 1.30 to 5.60, p=0.008). No significant
      heterogeneity was found among studies in the meta-analysis. CONCLUSIONS:
      Empirical fluoroquinolone prescriptions for pneumonia are associated with longer
      delays in diagnosis and treatment of pulmonary TB and a higher risk of developing
      fluoroquinolone-resistant M. tuberculosis.

PMID- 21195000
TI  - miR-182-mediated downregulation of BRCA1 impacts DNA repair and sensitivity to
      PARP inhibitors.
AB  - Expression of BRCA1 is commonly decreased in sporadic breast tumors, and this
      correlates with poor prognosis of breast cancer patients. Here we show that BRCA1
      transcripts are selectively enriched in the Argonaute/miR-182 complex and miR-182
      downregulates BRCA1 expression. Antagonizing miR-182 enhances BRCA1 protein
      levels and protects them from IR-induced cell death, while overexpressing miR-182
      reduces BRCA1 protein, impairs homologous recombination-mediated repair, and
      render cells hypersensitive to IR. The impaired DNA repair phenotype induced by
      miR-182 overexpression can be fully rescued by overexpressing miR-182-insensitive
      BRCA1. Consistent with a BRCA1-deficiency phenotype, miR-182-overexpressing
      breast tumor cells are hypersensitive to inhibitors of poly (ADP-ribose)
      polymerase 1 (PARP1). Conversely, antagonizing miR-182 enhances BRCA1 levels and
      induces resistance to PARP1 inhibitor. Finally, a clinical-grade PARP1 inhibitor
      impacts outgrowth of miR-182-expressing tumors in animal models. Together these
      results suggest that miR-182-mediated downregulation of BRCA1 impedes DNA repair
      and may impact breast cancer therapy.

PMID- 21195002
TI  - Prevalence and risk factors of diabetes in a community-based study in North
      India: the Chandigarh Urban Diabetes Study (CUDS).
AB  - AIMS: As there have been few studies in North India of the prevalence of diabetes
      within the past decade, this study aimed to assess the prevalence and risk
      factors associated with diabetes in the North Indian city of Chandigarh. METHODS:
      This cross-sectional survey of 2227 subjects (response rate: 94%), aged >=20
      years and representative of the urban Chandigarh population, was conducted from
      April 2008 to June 2009. Fasting plasma glucose (FPG) and 2-h plasma glucose
      (2hPG) following ingestion of 75 g of an anhydrous glucose equivalent were
      estimated by glucometer in all subjects except those with known diabetes, in whom
      only FPG was measured. Diagnosis of diabetes was based on 1999 WHO criteria. The
      collected prevalence data was age-standardized for the Chandigarh population, and
      multivariate logistic-regression analysis was used to correlate risk factors with
      the presence of diabetes. RESULTS: A total of 349 subjects (15.7%, 95% CI: 13.9
      16.9) were diabetic, comprising 210 (9.4%) with known diabetes and 139 (6.2%)
      with newly diagnosed diabetes, and 344 (15.4%, 95% CI: 14.3-17.1) subjects were
      prediabetic. The age-standardized prevalence of diabetes and prediabetes were
      11.1% (95% CI: 9.7-12.4) and 13.2% (95% CI: 11.8-14.6), respectively. Age >=50
      years, a family history of diabetes, BMI >=23 kg/m(2), abdominal obesity and
      hypertension were significantly and positively associated with the presence of
      diabetes, whereas educational status was negatively associated with diabetes
      (P<0.001 for all). CONCLUSION: The age-standardized prevalence of diabetes and
      prediabetes were 11.1% and 13.2%, respectively. Older age, family history of
      diabetes, obesity and hypertension were positively related, while educational
      status was negatively related, to the presence of diabetes.

PMID- 21195003
TI  - [Surgical management of hepatocellular carcinoma in 2010].
AB  - Radiofrequency ablation, partial or total hepatectomy represent curative
      treatment options for patients suffering from hepatocellular carcinoma in 2010.
      In this review article, the role (indication, limits, results) of hepatic
      resection and liver transplantation are discussed.

PMID- 21195004
TI  - Ureaplasma urealyticum destructive septic arthritis in a patient with systemic
      lupus erythematosus after rituximab therapy.

PMID- 21195005
TI  - Coronary artery aneurysms in Wegener's granulomatosis.
AB  - Atherosclerosis is the main cause of coronary artery aneurysm, however they can
      be observed in connective tissue diseases such as systemic lupus erythematosus
      and vasculitis. Kawasaki's disease and polyarteritis nodosa (PAN) are the
      systemic vasculitis that more often present coronary artery aneurysms. There are
      descriptions in the literature that small vessel vasculitis such as microscopic
      polyangiitis and PAN could develop coronary artery aneurysm, which are infrequent
      in other ANCA-associated vasculitis. Here, we report the case of a 25-year-old
      man who developed an extensive anterior myocardial infarct. The coronary
      angiogram showed coronary artery aneurysms, on laboratory ANCA C positivity with
      elevated levels of anti-proteinase 3 antibodies were present. He was treated with
      high doses of corticosteroids and cyclophosphamide with resolution of the
      aneurysms.

PMID- 21195006
TI  - Prevalence of generalized osteoarthritis in a population with knee
      osteoarthritis.
AB  - OBJECTIVE: To determine the prevalence of generalized osteoarthritis in patients
      with knee osteoarthritis. METHODS: Patients with knee osteoarthritis were
      recruited for a therapeutic trial via press announcement and selected based on
      American College of Rheumatology radioclinical criteria for femorotibial
      arthritis. Patients were asked to bring all their radiographs to the study
      visits, which included a physical examination. Each patient had an inclusion
      visit and a second visit 1 month later. The study physicians used a standardized
      chart to indicate clinical and radiographic evidence of osteoarthritis in each
      patient. At the hands and feet, the presence of clinical criteria was sufficient
      for the diagnosis of osteoarthritis. The shoulders and elbows were not assessed.
      Three criteria sets for generalized osteoarthritis were evaluated: Kellgren and
      Moore criteria (Heberden's nodes or interphalangeal osteoarthritis), ACR criteria
      (osteoarthritis of the spine and at least two other joints), and Dougados
      criteria (bilateral finger osteoarthritis or osteoarthritis of the spine and both
      knees). RESULTS: We included 302 patients for whom the side affected with knee
      osteoarthritis was known. Mean symptom duration was 5.9+/-5.7 years, mean number
      of painful flares was 10.1+/-9.4, mean number of joints with osteoarthritis was
      2.6+/-1.8, and mean body mass index was 29.5+/-5.3 kg/m(2). A family history of
      osteoarthritis was noted in 154 (51%) patients and spinal osteoarthritis in 148
      (49%) patients. Kellgren-Moore criteria for interphalangeal osteoarthritis were
      met in 42 (13.9%) patients, ACR criteria by 124 (41%) patients, and Dougados
      criteria by 127 (42%) patients. In all, 156 (52%) patients met at least one of
      the three definitions of generalized osteoarthritis. CONCLUSION: More than half
      the patients included in a therapeutic trial in knee osteoarthritis had
      generalized osteoarthritis with maximum symptoms at the knee at baseline. Some
      patients with osteoarthritis in multiple joints met none of the three criteria
      sets for generalized osteoarthritis. Further studies are needed to assess the
      sensitivity and specificity of current criteria sets and, if needed, to identify
      new criteria.

PMID- 21195007
TI  - [Omics as a tool for ART].

PMID- 21195008
TI  - [Is there any medical treatment to preserve fertility during chemotherapy in
      women?].
AB  - Intensive use of radio-chemotherapy has greatly improved the prognosis associated
      with cancer in young girl or women patients. However, improvement of the vital
      prognosis is frequently associated with impairment of fertility and premature
      ovarian failure. In vitro fertilization (IVF) followed by embryo cryopreservation
      is an available method, which needs a partner and a pretreatment stimulation.
      Ovarian and oocyte cryopreservation are techniques showing great promise.
      However, the nec plus ultra would be to be able to protect ovaries during
      chemotherapy. Since more than 10 years Gonadotropin releasing hormone (GnRH)
      analogues have been investigated as possible means to preserve fertility in young
      women. However, even recent prospective, randomized studies do not demonstrate
      clearly their effectiveness. To prevent primordial follicle apoptosis, an
      inhibitor of tysosine kinase, imatinib, has recently been proposed and positively
      evaluated in mice. It could represent an interesting hope to preserve female
      fertility during chemotherapy.

PMID- 21195009
TI  - [The university or interuniversity degrees for residents in gynecology
      obstetrics: Essential for our training?].

PMID- 21195010
TI  - Lead dioxide film sonoelectrodeposition in acidic media: Preparation and
      performance of stable practical anodes.
AB  - Practical lead dioxide anodes have been obtained by electrodeposition on glassy
      carbon and titanium substrates in the presence and in the absence of an
      ultrasound field. The films obtained by mechanical agitation on glassy carbon are
      strongly improved when the electrodeposition process is carried out with the
      ultrasound field, providing adherent deposits free from nodules and stress, but
      with pores appearing occasionally. These enhanced properties were not achieved by
      mechanical conditions, even when optimization of temperature, current density,
      additives and geometrical aspects was attempted. The best practical anodes were
      obtained by sonoelectrodeposition using specially treated titanium as substrate,
      providing comparable behavior to commercial electrodes.

PMID- 21195011
TI  - Study of single bubble sonoluminescence in phosphoric acid.
AB  - Sonoluminescence (SL) radiation from different solutions of phosphoric acid has
      been studied in the framework of a hydro-chemical simulation. By calculating the
      phase diagrams of an SL bubble in different concentrations of phosphoric acid,
      the optimum solution for acquiring maximum SL emission has been specified as the
      solution of around 30 wt.% acid. It is shown that the SL temperature and the
      number of particles inside the bubble at the time of SL emission are two
      important factors determining the optimum solution. Numerical calculation of the
      SL intensity shows that the optimum solution has an intensity of about 20 times
      greater than that of water. Also, contributions of different energy sources in
      creation of thermal energy of the bubble have been calculated. The result
      indicates that the work of external driving pressure is the most important factor
      to determine the ultimate thermal energy of the bubble at the time of SL
      emission. Based on this result, we have reasoned out that in the determination of
      the optimum solution, the role of viscosity of the acid solutions is more
      important than the vapor pressure.

PMID- 21195012
TI  - Gender distribution of patients with Parkinson's disease treated with subthalamic
      deep brain stimulation; a review of the 2000-2009 literature.
AB  - PURPOSE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been
      the mainstream surgical procedure for advanced Parkinson's disease (PD) during
      the last decade. Reports from a few individual centres have hinted that women who
      receive STN DBS are under-represented. We aimed to evaluate the gender
      distribution of patients with PD who had received STN DBS during the last ten
      years, and to discuss the findings in relation to studies on gender prevalence of
      PD. METHODS: A search of the PubMed database of clinical papers in English
      language related to STN DBS between 2000 and 2009 was conducted. Care was taken
      to minimize redundancies in reporting of published patients. The proportion of
      men and women were expressed in total and according to pre-defined geographic
      regions. RESULTS: One hundred and thirty five papers were eligible for review.
      The gender of the patients was specified in 119 papers on a total of 3880
      patients, of which 63% were men. According to geographic origin of publications,
      the percentage of men with STN DBS was 68% in North America, 62% in Europe, 69%
      in Australia and 50% in Asia. CONCLUSIONS: The proportion of male patients who
      undergo STN DBS seems to exceed the reported male/female ratio of patients with
      PD.

PMID- 21195013
TI  - A multi-level analysis of risk perception, poverty and sexual risk-taking among
      young people in Cape Town, South Africa.
AB  - Various studies have underscored the relevance of community-level factors to
      sexual behavior and HIV/AIDS prevention efforts in Africa. However, there is a
      paucity of research and theorizing in this area compared to the preponderance of
      prevention models that focus solely on individual-level factors. Using data from
      the Cape Area Panel Survey and hierarchical linear models, this study examines
      the effects of a combination of individual-level factors and community-level
      poverty on sexual behaviors. Male and female respondents who perceived themselves
      to be at great risk of HIV infection were less likely to indulge in risky sexual
      behaviors. For females, race and community-level poverty were confounded such
      that race mediated the effects of community-level poverty. Results from this
      study indicate that multiple rationalities affect sexual behaviors in Cape Town,
      South Africa and that there is a need to consider both the social embeddedness of
      sexual behaviors and the rational components of decision making when designing
      HIV/AIDS prevention programs.

PMID- 21195014
TI  - Intergenerational differences in antenatal care and supervised deliveries in
      Nigeria.
AB  - OBJECTIVE: To assess whether age cohort influences the likelihood of receiving
      antenatal care (ANC) and having a supervised delivery, before and after adjusting
      for other factors. DESIGN: Using data from the 2008 Nigeria Demographic and
      Health Survey, we grouped women into three distinct cohorts based on their year
      of birth: the young (1984-1993), the middle (1974-1983) and the older (1959-1973)
      cohorts. We applied multilevel logistic regression methods to assess the
      influence of age cohort on receiving ANC and having a supervised delivery among
      women (n=18,028) whose most recent birth occurred anytime in the five years
      preceding the survey. RESULTS: We identified belonging to the youngest age
      cohort, rural residence, lack of schooling, higher parity, residence in northern
      region and poor economic status as determinants of low uptake of ANC and
      supervised deliveries. CONCLUSION: Urgent efforts are needed in Nigeria to ensure
      that young women in particular receive ANC and have supervised deliveries. An
      agenda promoting a combination of individuals campaigning for change
      (particularly in northern Nigeria), communities raising awareness among men and
      women, and governmental and nongovernmental organizations working together to
      find practical solutions is an indispensable aim for saving the lives of many
      women and children who are at risk of dying of maternal and child-related
      diseases.

PMID- 21195015
TI  - Statistical modeling and recognition of surgical workflow.
AB  - In this paper, we contribute to the development of context-aware operating rooms
      by introducing a novel approach to modeling and monitoring the workflow of
      surgical interventions. We first propose a new representation of interventions in
      terms of multidimensional time-series formed by synchronized signals acquired
      over time. We then introduce methods based on Dynamic Time Warping and Hidden
      Markov Models to analyze and process this data. This results in workflow models
      combining low-level signals with high-level information such as predefined
      phases, which can be used to detect actions and trigger an event. Two methods are
      presented to train these models, using either fully or partially labeled training
      surgeries. Results are given based on tool usage recordings from sixteen
      laparoscopic cholecystectomies performed by several surgeons.

PMID- 21195017
TI  - Small molecule modulators of antioxidant response pathway.
AB  - Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that
      regulates Antioxidant Response Element (ARE)-mediated transcription of a plethora
      of antioxidant and protective genes to counteract the harmful effects of reactive
      oxygen species or environmental carcinogens. Studies have demonstrated that pre
      emptive activation of the Nrf2-ARE pathway reinforces the cellular defense
      mechanism against oxidative stress and leads to protection in a variety of
      disease models. Non-carcinogenic ARE inducers have been identified from a variety
      of chemical classes that enhance the transcriptional activity of Nrf2 through S
      alkylation of reactive cysteines within the cellular redox sensor protein Keap1
      (Kelch-like ECH associated protein 1). Here we review the currently known small
      molecule ARE inducers and their reported biological activities in various models.

PMID- 21195016
TI  - A magnetic resonance spectroscopy driven initialization scheme for active shape
      model based prostate segmentation.
AB  - Segmentation of the prostate boundary on clinical images is useful in a large
      number of applications including calculation of prostate volume pre- and post
      treatment, to detect extra-capsular spread, and for creating patient-specific
      anatomical models. Manual segmentation of the prostate boundary is, however, time
      consuming and subject to inter- and intra-reader variability. T2-weighted (T2-w)
      magnetic resonance (MR) structural imaging (MRI) and MR spectroscopy (MRS) have
      recently emerged as promising modalities for detection of prostate cancer in
      vivo. MRS data consists of spectral signals measuring relative metabolic
      concentrations, and the metavoxels near the prostate have distinct spectral
      signals from metavoxels outside the prostate. Active Shape Models (ASM's) have
      become very popular segmentation methods for biomedical imagery. However, ASMs
      require careful initialization and are extremely sensitive to model
      initialization. The primary contribution of this paper is a scheme to
      automatically initialize an ASM for prostate segmentation on endorectal in vivo
      multi-protocol MRI via automated identification of MR spectra that lie within the
      prostate. A replicated clustering scheme is employed to distinguish prostatic
      from extra-prostatic MR spectra in the midgland. The spatial locations of the
      prostate spectra so identified are used as the initial ROI for a 2D ASM. The
      midgland initializations are used to define a ROI that is then scaled in 3D to
      cover the base and apex of the prostate. A multi-feature ASM employing
      statistical texture features is then used to drive the edge detection instead of
      just image intensity information alone. Quantitative comparison with another
      recent ASM initialization method by Cosio showed that our scheme resulted in a
      superior average segmentation performance on a total of 388 2D MRI sections
      obtained from 32 3D endorectal in vivo patient studies. Initialization of a 2D
      ASM via our MRS-based clustering scheme resulted in an average overlap accuracy
      (true positive ratio) of 0.60, while the scheme of Cosio yielded a corresponding
      average accuracy of 0.56 over 388 2D MR image sections. During an ASM
      segmentation, using no initialization resulted in an overlap of 0.53, using the
      Cosio based methodology resulted in an overlap of 0.60, and using the MRS-based
      methodology resulted in an overlap of 0.67, with a paired Student's t-test
      indicating statistical significance to a high degree for all results. We also
      show that the final ASM segmentation result is highly correlated (as high as
      0.90) to the initialization scheme.

PMID- 21195018
TI  - Recent progress in industrial biocatalysis.
AB  - In recent years, several procedures have been reported for the development of
      biocatalytic processes. This review focuses on selected examples integrating
      biocatalysts into a variety of industrially interesting processes ranging from
      the manufacture of smaller, chiral speciality chemicals to the synthesis of more
      complex pharmaceutical intermediates. The use of rational protein design,
      multistep processes and de novo design of enzyme catalysts for the
      stereocontrolled preparation of important target structures is discussed.

PMID- 21195019
TI  - Electrochemical, catalytic and antimicrobial activity of N-functionalized
      tetraazamacrocyclic binuclear nickel(II) complexes.
AB  - The five binuclear nickel(II) complexes have been synthesized by the Schiff base
      condensation of 1,8-[bis(3-formyl-2-hydroxy-5-methyl)benzyl]-l,4,8,11
      tetraazacyclo-tetradecane (PC) with appropriate aliphatic diamines and nickel(II)
      perchlorate. All the five complexes were characterized by elemental and spectral
      analysis. The electronic spectra of the complexes show three d-d transition in
      the range of 550-1055 nm due to 3A2g->3T2g(F), 3A2g->3T1g(F) and 3A2g->3T1g(P).
      These spin allowed electronic transitions are characteristic of an octahedral
      Ni2+ center. Electrochemical studies of the complexes show two irreversible one
      electron reduction waves at cathodic region. The reduction potential of the
      complexes shifts towards anodically upon increasing the chain length of the
      macrocyclic ring. All the nickel(II) complexes show two irreversible one electron
      oxidation waves at anodic region. The oxidation potential of the complexes shift
      towards anodically upon increasing the chain length of the macrocyclic ring. The
      catalytic activities of the complexes were observed to be increase with increase
      the macrocyclic ring size. The observed rate constant values for the catalytic
      hydrolysis of 4-nitrophenyl phosphate are in the range of 5.85*10(-3) to 9.14*10(
      3) min(-1). All the complexes were screened for antimicrobial activity.

PMID- 21195020
TI  - Comparative evaluation of AMPLICOR HPV PCR and Linear Array assays on SurePath
      liquid-based Pap samples for the detection of high-risk HPV genotypes.
AB  - BACKGROUND: Persistent cervical infection with high-risk [HR] HPV is a causative
      factor for cancer. Liquid-based [L-Pap] Pap samples are convenient for HPV
      testing and SurePath samples have been least studied. Most HPV tests have
      multiple step protocols and testing laboratories experience large volumes of
      samples. OBJECTIVES: Using SurePath L-Pap residual samples the objectives were as
      follows: [1] to test the performance of AMP-HPV and LA-HPV. [2] To perform an
      agreement study between two laboratories for the AMP-HPV test and [3] to compare
      agreement of results between AMP-HPV and LA-HPV and HC2. STUDY DESIGN: Samples
      from 657 women were tested for Pap cytology then assayed for HR-HPV using AMP-HPV
      and LA-HPV tests. AMP-HPV performance was compared between 2 laboratories and
      agreement studies were conducted between AMP-HPV, LA-HPV and HC2. RESULTS: HR-HPV
      genotypes were associated with L-Pap readings as follows: HSIL 92% [23/25], LSIL
      73.6% [162/220], ASCUS 70.4% [131/186], normal 31.9% [72/226]. More women less
      than 30 were infected with HR-HPV and multiple genotypes regardless of the L-Pap
      reading. AMP-HPV and LA-HPV testing had an overall raw agreement with each other
      of 84.2% [Kappa 0.66] and each had agreement of 94% with HC2 testing of 133
      samples [Kappa 0.86/0.87]. AMP-HPV agreement between two laboratories was better
      at 93% [Kappa 0.84] compared to 76.1% [Kappa 0.40] when extraction was
      standardized. CONCLUSION: It is feasible to perform AMP-HPV and LA-HPV on
      SurePath samples to detect HR-HPV genotypes. HC2, AMP-HPV and LA-HPV showed
      strong agreement. The extraction component of the AMP-HPV assay needs careful
      attention to yield consistent results.

PMID- 21195021
TI  - A pauci-symptomatic case of documented Hantavirus (Puumala) infection in a
      patient under anti-TNF treatment.
AB  - We describe the case of an 18-yr-old male under anti-TNF treatment for Crohn's
      disease for more than 8 months. He developed fever and biological inflammatory
      syndrome without absolutely no accompanying sign or symptom or paraclinical
      abnormality despite extensive work-up performed in the context of his
      immunocompromised state. Symptoms disappeared after 10 days and a diagnosis of
      Puumala infection was made retrospectively on a serological basis. The case
      illustrates that anti-TNF treatment does not worsen the course of Puumala
      infection and could even be associated with a milder clinical picture.

PMID- 21195022
TI  - Epidemiological investigation of an outbreak of pandemic influenza A (H1N1) 2009
      in a boarding school: serological analysis of 1570 cases.
AB  - BACKGROUND: A large number of 2009 pandemic influenza A (H1N1) infections were
      localized in school populations. OBJECTIVES: To describe the epidemiology,
      clinical features and risk factors associated with an outbreak that occurred at a
      vocational boarding school in Guangzhou, P.R. China. STUDY DESIGN: Data were
      collected prospectively and retrospectively through the use of on-site doctors
      and a post-outbreak survey and blood collection. The survey was used to confirm
      symptoms, and to investigate a series of flu-related factors such as dormitory
      conditions, health habits, vaccine history and population contact history. Blood
      samples were taken for serological analysis. Pandemic H1N1 infection was
      initially confirmed by a real-time RT-PCR assay. Following the identification of
      the outbreak by the Guangzhou CDC on September 4, cases were diagnosed
      symptomatically and retrospectively by serological analysis using the
      hemagglutination inhibition assay and a neutralization assay. RESULTS: The
      infection rate was 32% (505/1570) and the attack rate was 22.2% (349/1570). The
      asymptomatic infection rate was 9.9% (156/1570). Sharing a classroom (OR=2.17,
      95% CI: 1.62-2.91) and dormitory space (OR=2.32, 95% CI: 1.84-2.93) was
      associated with higher rates of infection. Opening windows for ventilation was
      the only control measure that significantly protected against infection.
      CONCLUSION: Social isolation and quarantine should be used to prevent the spread
      of infection. Ventilation and a control of air flow between classrooms and dorms
      should be implemented as possible. School closures may be effective if
      implemented early.

PMID- 21195023
TI  - Comparable performance of TMA and Real-Time PCR in detecting minimal residual
      hepatitis C viraemia at the end of antiviral therapy.
AB  - BACKGROUND: Antiviral therapy for chronic hepatitis C may cause transient on
      treatment response followed by post-treatment relapse. OBJECTIVES: We have
      compared the prognostic value for post-treatment relapse of minimal hepatitis C
      residual viraemia detected at end-of-therapy by transcription mediated assay
      (TMA) and by Abbott RealTime PCR HCV assay. STUDY DESIGN: Minimal residual
      viraemia was investigated in 202 HCV patients who had completed a full course of
      Pegylated Interferon (PEG-IFN) plus ribavirin and were HCV-RNA negative by
      conventional PCR in two separate serum samples obtained during the last week of
      therapy and the results were then correlated with post-treatment outcome.
      RESULTS: Minimal residual viraemia was detected in 22/202 (11%, 95% CI: 7-16%)
      and in 28/202 (13.8%, 95% CI 10-19%) patients by TMA and by Abbott RealTime HCV
      assay, respectively, with 92% concordant results. Post-treatment relapse was seen
      in 81.8% (95% CI: 60-93%) of TMA positive and in 82.1% (95% CI: 64-92%) of Abbott
      RealTime HCV assay positive cases compared to 16.6% (95% CI: 12-23%) of TMA
      negative and 17.2% (95% CI: 12-23%) of Abbott RealTime HCV assay negative
      patients. CONCLUSIONS: These results indicate that TMA and the Abbott RealTime
      HCV assay have comparable sensitivity and specificity in identifying minimal
      residual viraemia at the end of antiviral therapy, with excellent predictive
      value for post-treatment relapse.

PMID- 21195024
TI  - Botulinum toxin has an increased effect when targeted toward the muscle's
      endplate zone: a high-density surface EMG guided study.
AB  - OBJECTIVES: To compare the effect of endplate-targeted injections of a low
      Botulinum neurotoxin type A (BoNT-A) dose with that of injections at defined
      distances from the motor endplate zone. METHODS: In eight healthy volunteers, the
      main endplate zones of the right and left extensor digitorum brevis (EDB) muscles
      were localized using high-density surface EMG. On the study side BoNT-A was
      injected at fixed distances from the endplate zone. On the control side, BoNT-A
      was administered into the endplate zone. Compound muscle action potential (CMAP)
      prior to the injection and 2, 12, and 24 weeks later were recorded. RESULTS: On
      the control side, the mean CMAP reduction 2 weeks after BoNT-A injection was
      79.3%. The difference in CMAP reduction between both EDB muscles was
      significantly related to the injection distance from the endplate zone.
      Increasing the injection distance by 1cm reduced the effect of BoNT-A by 46%.
      CONCLUSIONS: Guided injection of a reduced BoNT-A dose into the muscle's endplate
      zone(s) is a promising strategy for optimizing the therapeutic effectiveness of
      BoNT-A and for minimizing side-effects such as unwanted weakness of adjacent
      muscles. SIGNIFICANCE: Precise endplate-targeted injections increase the effect
      of BoNT-A and may thus prove to reduce required dosage and treatment costs.

PMID- 21195025
TI  - Sleep, depression and suicide.

PMID- 21195026
TI  - Revertant mosaicism in skin: natural gene therapy.
AB  - Revertant mosaicism is a naturally occurring phenomenon involving spontaneous
      correction of a pathogenic mutation in a somatic cell. Recent studies suggest
      that it is not a rare event and that it could be clinically relevant to
      phenotypic expression and patient treatment. Indeed, revertant cell therapy
      represents a potential 'natural gene therapy' because in vivo reversion obviates
      the need for further genetic correction. Revertant mosaicism has been observed in
      several inherited conditions, including epidermolysis bullosa, a heterogeneous
      group of blistering skin disorders. These diseases provide a useful model for
      studying revertant mosaicism because of the visual and accessible nature of skin.
      This overview highlights the latest developments in revertant mosaicism and the
      translational implications germane to heritable skin disorders.

PMID- 21195027
TI  - Circulating concentration of stem cell factor in serum of stimulated IVF
      patients.
AB  - Stem cell factor (SCF) plays a major role in haematopoiesis and spermatogenesis,
      and possibly female fertility. This study investigated the role of changes in SCF
      concentrations in 74 assisted conception patients. In group 1 (n=74) SCF
      concentration was assessed in serum and follicular fluid (FF) on the day of
      follicular puncture (FP) and compared in serum and FF in response to ovarian
      stimulation between low (n=25), moderate (n=26) and high (n=14) responders. In
      group 2 (n=30) serum for SCF assessment was collected throughout the menstrual
      cycle until gestation. SCF concentration related to the number of follicles in
      serum and in FF decreased from low to moderate and high responders (P<0.001);
      pregnancy rates were 20.0%, 34.6% and 50.1%, respectively (P=0.05). SCF in serum
      increased from stimulation days 6-8 to 9-11 and peaked on the day of human
      chorionic gonadotrophin injection (P=0.03). The SCF concentrations dropped
      slightly on the day of FP, increased significantly to the day of pregnancy
      confirmation and reached highest concentration (P=0.02) during gestation. SCF is
      involved in follicle development and may be a predictor of IVF outcome.

PMID- 21195028
TI  - Characterization of lactoferrin receptor on human spermatozoa.
AB  - Lactoferrin (LF) is abundant in human seminal plasma and on sperm surfaces.
      However, lactoferrin receptor (LFR) on human spermatozoa has not yet been
      reported. To study the expression, localization and characteristics of LFR on
      human spermatozoa, different experimental approaches were applied: LFR gene was
      amplified from a human testis cDNA library and recombinant LFR (rLFR) protein was
      produced in the expression vector Escherichia coli BL21 (DE3); human sperm
      membrane proteins were extracted and analysed via Western blot; the binding of LF
      to LFR was investigated by Far-Western blot, immunoprecipitation and
      autoradiography analysis and the localization of LFR on sperm surfaces was
      detected using immunofluorescence. LFR gene was amplified from a human testis
      cDNA library and the molecular weight of rLFR was 34kDa. The native LFR on human
      spermatozoa was a 136-kDa tetramer which was anchored to the sperm head and mid
      piece through glycophosphatidylinositol. LF could bind to LFR competitively in
      vitro. As far as is known, this study has elucidated for the first time that LFR
      was expressed at the testis level, was anchored to the sperm membrane by
      glycophosphatidylinositol during spermatogenesis. LFR may play important roles
      through binding to and mediating LF.

PMID- 21195029
TI  - Preliminary data on endoscopic treatment of vesicoureteric reflux with
      polyacrylate polyalcohol copolymer (Vantris(r)): surgical outcome following
      single injection.
AB  - PURPOSE: The aim of this study was to evaluate the efficacy of single injection
      of a new non-biodegradable agent (Vantris((r))) Manufactured by Promedon,
      Cordoba, Argentina for treatment of vesicoureteric reflux (VUR). PATIENTS AND
      METHODS: 38 children (11 males and 27 females) with a mean age of 5.3 +/- 3.8
      years underwent endoscopic treatment of VUR using Vantris. VUR was unilateral in
      17 and bilateral in 21 patients, comprising 59 renal refluxing units (RRU). The
      VUR was primary in 42 RRU and 17 comprised complex cases: 3 duplex systems, 1
      with prune belly syndrome, and 13 after failed previous endoscopic correction
      with Deflux((r)). VUR was Grade I in 5, II in 11, III in 23, IV in 15 and V in 5
      RRU. RESULTS: All patients completed 3 months of follow up. The reflux was
      corrected in 56 (94.9%) of the 59 RRU (35/38 patients) after a single injection.
      Of the 38 patients, 21 completed 1 year of follow up, at which time ultrasound
      demonstrated no change compared with 1 month after injection. Eight of these 21
      children underwent 1 year radionuclide cystography, and no reflux recurrence was
      shown. CONCLUSIONS: Our short-term data show that Vantris injection provides a
      high level of reflux resolution. Long-term follow up with this tissue-augmenting
      substance is required.

PMID- 21195030
TI  - Knowledge and practices about rabies among travel medicine consultants in Greece.
AB  - The number of travellers returning with animal bites from rabies enzootic areas
      has increased in Greece. The aim of this study was to assess the knowledge of
      travel-associated risk and preventive measures for rabies. A questionnaire was
      sent to Travel Medicine consultants in all prefectures. Of 100 Travel Medicine
      consultants, advice about rabies was given to long-term travellers, business
      travellers, travellers to rural areas, and travellers engaged in animal
      activities in rabies enzootic countries by 44%, 22%, 58%, and 75% of them
      respectively. Avoidance of animals, post-exposure medical assistance, return back
      to their country, and special caution about children was recommended by 89%, 95%,
      8%, and 65% of them, respectively. Rabies pre-exposure vaccination was
      recommended for travellers to rural areas, long-term travellers, and travellers
      engaged in animal activities by 61%, 35%, and 81% of them, respectively.
      Regarding post-exposure vaccination, 78% and 37% answered correctly with regards
      to travellers with no pre-exposure prophylaxis and travellers with pre-exposure
      prophylaxis, respectively. Counselling about rabies and management of risk
      exposure needs to be improved. Our findings indicate the need to promote
      continuous training in Travel Medicine in Greece and provide practical
      information about rabies prophylaxis.

PMID- 21195031
TI  - Newly presenting psychogenic nonepileptic seizures: incidence, population
      characteristics, and early outcome from a prospective audit of a first seizure
      clinic.
AB  - There are few published population-based data for psychogenic nonepileptic
      seizures (PNES). We prospectively identified first presentations of PNES from a
      population of 367,566, over 3 years. PNES were diagnosed in 68 patients, in 54 of
      whom the diagnosis was confirmed by video/EEG recording, indicating an incidence
      of 4.90/100,000/year. Median diagnostic delay was 0.6 +/- 0.2 year. At
      presentation with PNES, our patients already had high rates of psychological
      morbidity, medically unexplained symptoms other than PNES, and economic
      dependence. At 3 months postdiagnosis, 27 of 54 patients (50.0%) were spell free.
      For 24 of the 27 patients (88.9%), spells ceased immediately on communication of
      the diagnosis. At 6 months, 24 of 54 patients (44.4%) were spell free. Poor early
      outcome was predicted by unemployment. Our data suggest that early outcome is
      good in patients with recent-onset PNES, but some patients relapse quickly.

PMID- 21195032
TI  - Higher evening antiepileptic drug dose for nocturnal and early-morning seizures.
AB  - We describe 17 children with nocturnal or early-morning seizures who were
      switched to a proportionally higher evening dose of antiepileptic drugs and were
      retrospectively reviewed for seizure outcome and side effects. Of 10 children
      with unknown etiology, clinical presentation was consistent with nocturnal
      frontal lobe epilepsy (NFLE) in 5 and benign epilepsy with centrotemporal spikes
      (BECTS) in 3. After a mean follow-up of 5.3 months, 15 patients were classified
      as responders; 11 of these became seizure free (5 NFLE, 1 BECTS, 5 with
      structural lesions) and 4 (2 BECTS, 2 with structural lesions) experienced 75-90%
      reductions in seizures. Among two nonresponders, seizures in one had failed to
      resolve with epilepsy surgery. Nine subjects (53%) received monotherapy after
      dose modification, and none presented with worsening of seizures. Two complained
      of transient side effects (fatigue/somnolence). Differential dosing led to
      seizure freedom in 64.7% (11/17) of patients, and 88.2% (15/17) experienced >=
      50% reductions in seizures.

PMID- 21195033
TI  - May migraine post-patent foramen ovale closure sustain the microembolic genesis
      of cortical spread depression?
AB  - BACKGROUND: Cortical spreading depression has been suggested to be the main
      substrate for migraine, but its pathobiology is not completely understood.
      Recently, the microembolic hypothesis as a promoting factor of cortical spreading
      depression has been demonstrated in an animal model. Our study is aimed to
      present a series of patients in whom early migraine attacks immediately after
      closure procedure predicted migraine with aura resolution on the long term,
      suggesting a role for microembolization in migraine genesis. METHODS: Our study
      consisted of 42 patients with migraine (36 female, mean age 35+/-6.7 years, mean
      Migraine Disability Assessment Score 29.9+/-9) and previous stroke who underwent
      transcatheter PFO closure during the last 2 years at the Rovigo General Hospital
      using different devices selected on the basis of specific anatomies. Procedural,
      technical, and clinical variables have been recorded and analyzed searching for
      potential relationships among postprocedural migraine, migraine improvement, and
      microembolization. RESULTS: Sixteen patients (38%) experienced a migraine attack
      of mean duration 3.5+/-2.4 h immediately (<60 min) after closure procedure. These
      patients more frequently had a severe migraine with aura and a permanent shunt on
      transcranial Doppler. There were no differences in terms of procedure time,
      occlusion time, and type of device used. After a mean follow-up of 32.2+/-10.6
      months, only patients with postprocedural migraine attacks reported resolution of
      aura and a significant improvement in migraine symptoms. CONCLUSIONS: Our series
      seem to indirectly confirm in vivo the experimental animal data of
      microembolization-driven cortical spreading depression. It also confers the
      recent hypothesis about air microbubble-induced cerebral deoxygenation linking
      the micromebolic hypothesis with cortical spreading depression.

PMID- 21195034
TI  - Peripheral embolic events during endovascular treatment of infra-inguinal chronic
      total occlusion.
AB  - Reliance on angiographic detection of peripheral embolic events during
      endovascular treatment of peripheral arterial disease not only underestimates its
      true incidence but is the leading cause for underdeveloped embolic protection
      strategies during peripheral arterial interventions. Detection of distal embolic
      signals especially during percutaneous treatment of infra-inguinal chronic total
      occlusions (CTO) remains unknown. We report Doppler ultrasound detection of
      distal embolic signals, during phases of percutaneous intervention involving
      recanalization of a superficial femoral artery CTO.

PMID- 21195035
TI  - Physical interaction between archaeal DNA repair helicase Hel308 and Replication
      Protein A (RPA).
AB  - Hel308 is a super-family 2 helicase in archaea with homologues in higher
      eukaryotes (HelQ and PolQ) that contribute to repair of DNA strand crosslinks
      (ICLs). However, the contribution of Hel308 to repair processes in archaea is far
      from clear, including how it co-operates with other proteins of DNA replication,
      repair and recombination. In this study we identified a physical interaction of
      Hel308 with RPA. Hel308 did not interact with SSB, and interaction with RPA
      required a conserved amino acid motif at the Hel308 C-terminus. We propose that
      in archaea RPA acts as a platform for loading of Hel308 onto aberrant single
      stranded DNA (ssDNA) that arises at blocked replication forks. In line with data
      from a human Hel308 homologue, the helicase activity of archaeal Hel308 was only
      modestly stimulated (1.5-2 fold) by RPA under some conditions, and much less so
      than for other known interactions between helicases and single strand DNA (ssDNA)
      binding proteins. This supports a model for RPA localising Hel308 to DNA damage
      sites in archaea, rather than it directly stimulating the mechanism of helicase
      unwinding.

PMID- 21195036
TI  - The impact of nocturnal oxygen desaturation on quality of life in cystic
      fibrosis.
AB  - BACKGROUND: Nocturnal oxyhaemoglobin desaturation is common in cystic fibrosis
      (CF) but the effect on quality of life (QoL) remains unknown. METHODS: Sixty
      stable CF outpatients with mean age 31+/-8 years (mean+/-1 SD), BMI 20.8+/-3.2
      kg/m(2) and FEV(1) 42+/-13% predicted had arterial blood gas sampling, lung
      function testing, overnight pulse oximetry and completed the CF QoL
      questionnaire, Epworth Sleepiness Scale and Medical Research Council dyspnoea
      scale. RESULTS: 11 (18%) of the CF patients were 'desaturators,' (SpO(2)<90% for
      >=30% recording time on overnight oximetry). Desaturators had greater difficulty
      performing their treatments (39+/-22 vs 61+/-26, p<0.01) and more exertional
      dyspnoea (3.2+/-0.8 vs 2.0+/-0.9, p<0.001) than non-desaturators after
      controlling for the effects of FEV(1), awake PaO(2) and PaCO(2) (adjusted p
      values <0.01 and 0.04 respectively). CONCLUSIONS: Nocturnal oxyhaemoglobin
      desaturation is associated with impaired QoL, independent of the effects of lung
      function and awake gas exchange, in stable CF outpatients with moderate to severe
      lung disease.

PMID- 21195037
TI  - Validation of insulin secretion indices in cystic fibrosis.

PMID- 21195038
TI  - Quantification of 3-deazaneplanocin A, a novel epigenetic anticancer agent, in
      rat biosamples by hydrophilic interaction liquid chromatography-tandem mass
      spectrometric detection.
AB  - A sensitive and selective LC-MS/MS based bioanalytical method was developed and
      validated for the quantification of 3-deazaneplanocin A (DZNep), a novel
      epigenetic anti-tumor drug candidate, in Sprague-Dawley (SD) rat biosamples
      (plasma, urine, feces and tissue samples). The method comprises a phenylboronic
      acid (PBA)-containing solid phase extraction procedure, serving for binding and
      clean-up of DZNep in rat biosamples spiked with tubercidin (as internal
      standard). The analytes were separated on an Agilent hydrophilic interaction
      chromatography (HILIC) column. LC-MS/MS in positive ion mode was used to perform
      multiple reaction monitoring at m/z of 263/135 and 267/135 for DZNep and
      tubercidin, respectively. The limit of quantification (LOQ) of DZNep in rat
      biosamples was 20 ng/mL. The data of intra-day and inter-day accuracy were within
      15% of nominal concentration while the precision (relative standard deviation)
      less than 10% for all biosamples. The extraction recoveries for DZNep and
      tubercidin were consistent and reproducible (around 80%) and the matrix effects
      were negligible (around 10% suppression) in all biosamples. This method was
      demonstrated to be applicable for pharmacokinetic studies of DZNep in SD rats.

PMID- 21195039
TI  - The physical stature of Jewish men in Poland in the second half of the 19th
      century.
AB  - Since 1843 Jews inhabiting the Kingdom of Poland were obliged to serve in the
      Russian army and therefore were examined by draft boards on a par with
      Christians. We explore the trends in the height of recruits by religion and place
      of birth. Basing on samples drawn from 21-year-old conscripts born between 1845
      and 1892 we find that Jewish conscripts were shorter than the Christians by 2.5
      cm at the beginning of the period under scrutiny and the difference exceeded 4 cm
      in the 1890s. The height of Jewish conscripts inhabiting provincial towns
      declined in the late 1880s and in the early 1890s was about the same as in the
      1840s, i.e. 161 cm. The socioeconomic crisis of provincial towns caused a massive
      migration to Warsaw and abroad as well. In the 1870s the stature of Warsaw and
      provincial Jews was similar, but in the early 1890s men from Warsaw were by 2 cm
      taller than provincial Jews. The height gap mirrors the difference in the
      standard of living between Warsaw and provincial towns.

PMID- 21195040
TI  - Comment to: "Cigarette smoking and appendectomy: effect on clinical course of
      diverticulosis".

PMID- 21195041
TI  - High-dose mesalazine treatment for ulcerative colitis patients who relapse under
      low-dose maintenance therapy.
AB  - BACKGROUND: Mesalazine is often used to maintain remission in patients with
      ulcerative colitis. AIM: To investigate if increasing the dose of mesalazine is
      safe and effective for patients with ulcerative colitis who relapse under low
      dose maintenance therapy. METHODS: Ninety consecutive patients who relapsed
      during maintenance therapy with oral mesalazine at 1.5-2.25g/day were included.
      All patients had mildly or moderately active ulcerative colitis at entry, and
      were treated with oral mesalazine at 4.0g/day for the following 8 weeks. At entry
      and week 8, endoscopic examinations were carried out to assess the severity of
      endoscopic inflammation. The primary as well as the secondary endpoints were
      clinical and endoscopic improvements at week 8. RESULTS: No patient experienced
      any serious side effect, and the treatment with 4.0g/day mesalazine over the 8
      week period was well tolerated by all patients. Fifty-nine patients (66%)
      achieved clinical improvement in stool frequency and/or rectal bleeding including
      40 (44%) with clinical remission (normal stool frequency and no rectal bleeding).
      Forty-three patients (48%) showed endoscopic improvement including 25 (28%) with
      endoscopic remission. CONCLUSIONS: Increasing the dose of mesalazine up to
      4.0g/day appeared to be safe and effective for patients who relapsed under low
      dose, 1.5-2.25g/day maintenance therapy.

PMID- 21195042
TI  - Lansoprazole-induced microscopic colitis: an increasing problem? Results of a
      prospecive case-series and systematic review of the literature.
AB  - BACKGROUND: Microscopic colitis (MC), comprising lymphocytic and collagenous
      colitis (LC, CC), causes chronic diarrhoea. Lansoprazole can cause MC. Likelihood
      criteria defining the causative relationship between drugs and MC have not been
      applied to lansoprazole, nor has lansoprazole-related-MC been characterized. AIM:
      To analyse a series of lansoprazole-related MC cases, and characterize
      lansoprazole-related CC and LC. METHODS: Cases were diagnosed over 23 months and
      causal relationship evaluated by established likelihood criteria. A systematic
      Medline search was conducted and publications analysed. RESULTS: Eight patients
      had lansoprazole-related MC. In all cases chronological and causality likelihood
      scores supported lansoprazole causative role. Discontinuation determined
      resolution without further treatment. Twenty-five cases of lansoprazole-related
      MC from 10 publications were grouped with the present series, and differences
      between CC and LC analysed. CC cases had more macroscopic alterations at
      colonoscopy (72.2 vs. 6.6%; p=0.0002). Time between lansoprazole start and
      symptoms onset was longer for CC (median 60 vs. 28 days; p=0.03). CONCLUSIONS:
      Peculiar features of lansoprazole-related CC were described through the analysis
      of a newly diagnosed lansoprazole-related MC series in which the causative role
      of lansoprazole was for the first time defined by established likelihood
      criteria, and by pooled evaluation with other cases retrieved by a systematic
      literature review.

PMID- 21195043
TI  - [Hot water epilepsy: a rare form of reflex epilepsy].

PMID- 21195044
TI  - Intestinal parasites in immigrants in the city of Naples (southern Italy).
AB  - The present study was aimed at carrying out a cross-sectional copromicroscopic
      survey of helminths and intestinal protozoa in immigrants in Naples (southern
      Italy). Between October 2008 and November 2009, a total of 514 immigrants were
      tested comparing the FLOTAC dual technique and the ethyl acetate concentration
      technique. Combined results of the two techniques served as a diagnostic 'gold'
      standard and revealed an overall prevalence of parasitic infections of 61.9%
      (318/514). The ethyl acetate concentration technique detected a low number of
      positive results (49.0%) and this was confirmed for each helminth/protozoa
      species detected. Among helminths, Trichuris trichiura (3.9%), hookworms (3.7%)
      and Ascaris lumbricoides (1.4%) were the most prevalent. Strongyloides
      stercoralis (0.4%), Enterobius vermicularis (0.4%), Schistosoma mansoni (1.0%),
      Hymenolepis nana (1.6%) and Taenia spp. (0.2%) were also found, as well as
      zoonotic helminths, as Trichostrongylus spp. (0.8%) and Dicrocoelium dendriticum
      (0.8%). As regard to pathogenic protozoa, Blastocystis hominis was the most
      commonly detected (52.7%), followed by Entamoeba histolytica/Entamoeba
      dispar/Entamoeba moshkovskii (11.9%) and Giardia duodenalis (4.5%). Several
      issues concerning diagnosis, epidemiology and public health impact of parasitic
      infections in immigrants are offered for discussion. In conclusion, the present
      paper pointed out the need of better diagnosis and cure of the immigrant
      population in order to improve access to health care of this neglected and
      marginalised population group, for its own protection and care.

PMID- 21195045
TI  - Acanthamoeba T3, T4 and T5 in swimming-pool waters from Southern Brazil.
AB  - Species of Acanthamoeba, known to cause keratitis (AK) and granulomatous
      encephalitis in humans are frequently isolated from a variety of water sources.
      In this study, 13 Acanthamoeba isolates from swimming pools were classified at
      the genotype level based on the sequence analysis of the Acanthamoeba small
      subunit rRNA gene. Nine of the 13 isolates were genotype T5, three were genotype
      T4, and one was T3. Several genotypes have been reported worldwide as causative
      agents of AK, including genotypes T3, T4, and T5. The present study indicates
      that genotype T5 is a common contaminant in swimming-pool water.

PMID- 21195046
TI  - Impact of Schistosoma haematobium infection on urinary tract pathology,
      nutritional status and anaemia in school-aged children in two different endemic
      areas of the Niger River Basin, Mali.
AB  - The aim of the present study was to contribute to define urinary schistosomiasis
      related morbidity indicators and to understand the relationship between infection
      intensity and disease burden among school-aged children in different endemic
      areas of Mali. A cross sectional study was undertaken in two different endemic
      settings: Koulikoro district, along the river and Selingue dam area in the Niger
      River Basin in order to compare and describe morbidity related to Schistosoma
      haematobium infection. A total of 667 children aged 7-14 were enrolled in the
      study. Among these, 333 were from Koulikoro district (175 boys and 158 girls) and
      334 from Selingue dam area (169 boys and 165 girls). The overall prevalence of S.
      haematobium in the two areas was 91.5%; Koulikoro (97.0%) and Selingue (85.9%)
      and this difference was significant after adjusting for age, sex and clustering
      within villages. Prevalence of heavy infection (>= 50 eggs per 10 ml of urine),
      57.6% in Koulikoro and 43.8% in Selingue, did not differ significantly after
      adjusting for age, sex and clustering within villages. The transmission of
      Schistosoma mansoni was mainly confined to Selingue dam area (12.5%) and was
      nearly absent in Koulikoro district (1.1%). Blood in urine was the most
      frequently reported clinical symptom, more common in Koulikoro (76.8%) than in
      Selingue (57.6%). In a multivariable logistic regression model adjusting for sex,
      age group, egg intensity category and clustering within villages, Selingue had
      higher prevalence of macro-haematuria, urinary tract pathology, upper urinary
      tract pathology and total pathology than Koulikoro, while micro-haematuria did
      not differ between the two areas. Morbidity measures increased to some extent
      with egg intensity category, especially micro-haematuria. The results obtained
      from this study are of importance for planning intervention as for monitoring and
      evaluation of control in different endemic settings in Mali.

PMID- 21195047
TI  - Spectroscopic characterization of cytochrome P450 Compound I.
AB  - The cytochrome P450 protein-bound porphyrin complex with the iron-coordinated
      active oxygen atom as Fe(IV)O is called Compound I (Cpd I). Cpd I is the
      intermediate species proposed to hydroxylate directly the inert carbon-hydrogen
      bonds of P450 substrates. In the natural reaction cycle of cytochrome P450 Cpd I
      has not yet been detected, presumably because it is very short-lived. A great
      variety of experimental approaches has been applied to produce Cpd I artificially
      aiming to characterize its electronic structure with spectroscopic techniques. In
      spite of these attempts, none of the spectroscopic studies of the last decades
      proved capable of univocally identifying the electronic state of P450 Cpd I. Very
      recently, however, Rittle and Green [9] have shown that Cpd I of CYP119, the
      thermophilic P450 from Sulfolobus acidocaldarius, is univocally a Fe(IV)O
      porphyrin radical with the ferryl iron spin (S=1) antiferromagnetically coupled
      to the porphyrin radical spin (S'=1/2) yielding a S(tot)=1/2 ground state very
      similar to Cpd I of chloroperoxidase from Caldariomyces fumago. In this mini
      review the efforts to characterize Cpd I of cytochrome P450 by spectroscopic
      methods are summarized.

PMID- 21195048
TI  - Roles of PsbI and PsbM in photosystem II dimer formation and stability studied by
      deletion mutagenesis and X-ray crystallography.
AB  - PsbM and PsbI are two low molecular weight subunits of photosystem II (PSII),
      with PsbM being located in the center, and PsbI in the periphery, of the PSII
      dimer. In order to study the functions of these two subunits from a structural
      point of view, we crystallized and analyzed the crystal structure of PSII dimers
      from two mutants lacking either PsbM or PsbI. Our results confirmed the location
      of these two subunits in the current crystal structure, as well as their absence
      in the respective mutants. The relative contents of PSII dimers were found to be
      decreased in both mutants, with a concomitant increase in the amount of PSII
      monomers, suggesting a destabilization of PSII dimers in both of the mutants. On
      the other hand, the accumulation level of the overall PSII complexes in the two
      mutants was similar to that in the wild-type strain. Treatment of purified PSII
      dimers with lauryldimethylamine N-oxide at an elevated temperature preferentially
      disintegrated the dimers from the PsbM deletion mutant into monomers and CP43
      less monomers, whereas no significant degradation of the dimers was observed from
      the PsbI deletion mutant. These results indicate that although both PsbM and PsbI
      are required for the efficient formation and stability of PSII dimers in vivo,
      they have different roles, namely, PsbM is required directly for the formation of
      dimers and its absence led to the instability of the dimers accumulated. On the
      other hand, PsbI is required in the assembly process of PSII dimers in vivo; once
      the dimers are formed, PsbI was no longer required for its stability.

PMID- 21195049
TI  - Regulation of electron transport in C(3) plant chloroplasts in situ and in
      silico: short-term effects of atmospheric CO(2) and O(2).
AB  - In this work, we have investigated the effects of atmospheric CO(2) and O(2) on
      induction events in Hibiscus rosa-sinensis leaves. These effects manifest
      themselves as multiphase kinetics of P(700) redox transitions and non-monotonous
      changes in chlorophyll fluorescence. Depletion of CO(2) and O(2) in air causes a
      decrease in linear electron flux (LEF) and dramatic lowering of P(700)(+) level.
      This is explained by the impediment to electron efflux from photosystem 1 (PS1)
      at low acceptor capacity. With the release of the acceptor deficit, the rate of
      LEF significantly increases. We have found that oxygen promotes the outflow of
      electrons from PS1, providing the rise of P(700)(+) level. The effect of oxygen
      as an alternative electron acceptor becomes apparent at low and ambient
      concentrations of atmospheric CO(2) < or = 0.06-0.07%). A decrease in LEF at low
      CO(2) is accompanied by a significant (about 3-fold) rise of non-photochemical
      quenching (NPQ) of chlorophyll fluorescence. Such an increase in NPQ can be
      explained by more significant acidification of the thylakoid lumen. This occurs
      due to lessening the proton flux through the ATP synthases caused by a decrease
      in the ATP consumption in the Bassham-Benson-Calvin (BBC) cycle. pH-dependent
      mechanisms of electron transport control have been described within the frames of
      our mathematical model. The model describes the reciprocal changes in LEF and NPQ
      and predicts the redistribution of electron fluxes on the acceptor side of PS1.
      In particular, the contribution of cyclic electron flow around PS1 (CEF1) and
      water-water cycle gradually decays during the induction phase. This result is
      consistent with experimental data indicating that under the steady-state
      conditions the contribution of CEF1 to photosynthetic electron transport in
      Hibiscus rosa-sinensis is insignificant (< or = 10%).

PMID- 21195050
TI  - The pore properties of human nociceptor channel TRPA1 evaluated in single channel
      recordings.
AB  - TRPA channels detect stimuli of different sensory modalities, including a broad
      spectrum of chemosensory stimuli, noxious stimuli associated with tissue damage
      and inflammation, mechanical stimuli, and thermal stimuli. Despite a growing
      understanding of potential modulators, agonists, and antagonists for these
      channels, the exact mechanisms of channel regulation and activation remain mostly
      unknown or controversial and widely debated. Relatively little is also known
      about the basic biophysical parameters of both native and heterologously
      expressed TRPA channels. Here we use conventional single channel inside-out and
      outside-out patch recording from the human TRPA1 channel transiently expressed in
      human embryonic kidney 293T cells to characterize the selectivity of the channel
      for inorganic mono-/divalent and organic monovalent cations in the presence of
      allylisothiocyanate (AITC). We show the relative permeability of the hTRPA1
      channel to inorganic cations to be:and to organic cations:Na(+)(1.0)>=
      dimethylamine (0.99)>trimethylamine (0.7)>tetramethylammonium (0.4)>N-methyl-d
      glucamine (0.1). Activation of the hTRPA1 channels by AITC appears to recruit the
      channels to a conformational state with an increased permeability to large
      organic cations. The pore of the channels in this state can be characterized as
      dilated by approximately 1-2.5 A. These findings provide important insight into
      the basic fundamental properties and function of TRPA1 channels in general and
      human TRPA1 channel in particular.

PMID- 21195051
TI  - Activated expression of cardiac adenylyl cyclase 6 reduces dilation and
      dysfunction of the pressure-overloaded heart.
AB  - BACKGROUND AND OBJECTIVE: Cardiac-directed adenylyl cyclase 6 (AC6) expression
      attenuates left ventricular (LV) hypertrophy and dysfunction in cardiomyopathy,
      but its effects in the pressure-overloaded heart are unknown. METHODS: Mice with
      cardiac-directed and regulated expression of AC6 underwent transaortic
      constriction (TAC) to induce LV pressure overload. Ten days prior to TAC, and for
      the duration of the 4 week study, cardiac myocyte AC6 expression was activated in
      one group (AC-On) but not the other (AC-Off). Multiple measures of LV systolic
      and diastolic function were obtained 4 weeks after TAC, and LV samples assessed
      for alterations in Ca2+ signaling. RESULTS: LV contractility, as reflected in the
      end-systolic pressure-volume relationship (Emax), was increased (p=0.01) by
      activation of AC6 expression. In addition, diastolic function was improved
      (p<0.05) and LV dilation was reduced (p<0.05). LV samples from AC-On mice showed
      reduced protein expression of sodium/calcium exchanger (NCX1) (p<0.05), protein
      phosphatase 1 (PP1) (p<0.01), and increased phosphorylation of phospholamban
      (PLN) at Ser16 (p<0.05). Finally, sarcoplasmic reticulum (SR) Ca2+ content was
      increased in cardiac myocytes isolated from AC-On mice (p<0.05). CONCLUSIONS:
      Activation of cardiac AC6 expression improves function of the pressure-overloaded
      and failing heart. The predominant mechanism for this favorable adaptation is
      improved Ca2+ handling, a consequence of increased PLN phosphorylation, reduced
      NCX1, reduced PP1 expression, and increased SR Ca2+ content.

PMID- 21195052
TI  - Dysregulation of angiogenesis-related microRNAs in endothelial progenitor cells
      from patients with coronary artery disease.
AB  - Endothelial progenitor cells (EPCs) play an important role in vascular repair and
      maintenance of vascular homeostasis through re-endothelialization and
      neovascularization. Cardiovascular risk factors that contribute to coronary
      artery disease (CAD) have been shown to negatively impact EPCs, although the
      mechanisms are poorly understood. MicroRNAs (miRNAs) which negatively regulate
      gene expression at the post-transcriptional level have been shown to impact
      endothelial cell (EC) angiogenic actions, but little is known about their role in
      modulating EPC function. In this study we first investigated if EPCs expressed EC
      specific, angiogenesis-related miRNAs; then determined whether the expression of
      these miRNAs was altered in EPCs from CAD patients as compared with healthy
      controls. Furthermore, we examined if atorvastatin, known to increase circulating
      EPC numbers, had any effect on EPC miRNA expression. We found EPCs produced miR
      126, miR-130a, miR-221, miR-222 and miR-92a which have thus far been identified
      as the most important angiogenic miRNAs. Dysregulation of these miRNAs was
      detected in EPCs from CAD patients and atorvastatin treatment selectively
      impacted miRNA expression in EPCs. Our data provide evidence that angiogenic
      miRNAs might play an important role in the control of EPC function, and that
      their dysregulation might contribute to EPC dysfunction in patients suffering
      from coronary artery disease. These findings might lead to the development of
      novel therapeutic modalities for the prevention and treatment of CAD.

PMID- 21195053
TI  - Sprouty2 controls proliferation of palate mesenchymal cells via fibroblast growth
      factor signaling.
AB  - Cleft palate is one of the most common craniofacial deformities. The fibroblast
      growth factor (FGF) plays a central role in reciprocal interactions between
      adjacent tissues during palatal development, and the FGF signaling pathway has
      been shown to be inhibited by members of the Sprouty protein family. In this
      study, we report the incidence of cleft palate, possibly caused by failure of
      palatal shelf elevation, in Sprouty2-deficient (KO) mice. Sprouty2-deficient
      palates fused completely in palatal organ culture. However, palate mesenchymal
      cell proliferation estimated by Ki-67 staining was increased in Sprouty2 KO mice
      compared with WT mice. Sprouty2-null palates expressed higher levels of FGF
      target genes, such as Msx1, Etv5, and Ptx1 than WT controls. Furthermore,
      proliferation and the extracellular signal-regulated kinase (Erk) activation in
      response to FGF was enhanced in palate mesenchymal cells transfected with
      Sprouty2 small interfering RNA. These results suggest that Sprouty2 regulates
      palate mesenchymal cell proliferation via FGF signaling and is involved in
      palatal shelf elevation.

PMID- 21195054
TI  - Exploring calmodulin-related proteins, which mediate development of hypertension,
      in vascular tissues of spontaneous hypertensive rats.
AB  - Calmodulin (CaM) is associated with a variety of cell functions including
      inflammation, apoptosis, and muscular contraction. It is recently clarified that
      some CaM-related proteins are responsible for cardiovascular diseases. We
      therefore explored CaM-related proteins that mediate hypertensive vascular
      diseases. Expression levels of six CaM-related proteins with almost unknown
      function in blood vessels were examined in aorta and mesenteric artery from
      spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) by Western
      blotting. In aorta from SHR, eukaryotic elongation factor (eEF)2 kinase (eEF2K)
      and death-associated protein kinase (DAPK)3 protein increased compared with WKY,
      while Ca(2+)/CaM-dependent protein kinase IIdelta, histone deacetylases (HDAC)4
      and HDAC5 protein decreased. In mesenteric artery from SHR, eEF2K, HDAC4 and
      DAPK3 protein increased compared with WKY, while HDAC5 decreased. Our findings
      demonstrate that expression levels of several CaM-related proteins are changed in
      vascular tissues of SHR and suggest that CaM-related proteins might be at least
      in part related to the pathogenesis of hypertensive vascular diseases.

PMID- 21195055
TI  - Single point mutation of microRNA may cause butterfly effect on alteration of
      global gene expression.
AB  - MicroRNAs (miRNAs) are short nucleotide RNAs that negatively regulate gene
      expression at the post-transcriptional level. Partially double-stranded miRNAs
      interact with an RNA-induced silencing complex (RISC) where one strand termed the
      guide strand is selected, while the partner strand accumulates at a lower level
      and is presumed to be degraded. The miRNA-loaded RISC then binds to target mRNAs
      through imperfect complementary sequences located in the 3'UTR and causes
      translation inhibition. One miRNA may negatively regulate hundreds of target
      mRNAs. In this study, a pre-miR-155 mutant was used to elucidate that a single
      mutation creating a mismatch near the 3' end of miR-155 led to a shift in strand
      selection, causing an increased selection of miR-155(*) and a decreased selection
      of miR-155, thereby fine-tuning the translation of their target genes.
      Consequently, this resulted in a butterfly effect on global gene expression.
      Indeed, nearly half of the genes we analyzed in this study showed altered
      expression. Provided that over 800 miRNAs have been identified in humans to date,
      mutation of miRNA is expected to play a critical role in species evolution and
      individual diversity.

PMID- 21195056
TI  - Bortezomib and sphingosine kinase inhibitor interact synergistically to induces
      apoptosis in BCR/ABl+ cells sensitive and resistant to STI571 through down
      regulation Mcl-1.
AB  - Interactions between the proteasome inhibitor, bortezomib, and the sphingosine
      kinase (SPK1) inhibitor, SKI, were examined in BCR/ABL human leukemia cells.
      Coexposure of K562 or chronic myeloid leukemia (CML) cells from patients to
      subtoxic concentrations of SKI (10 MUM) and bortezomib (100 nM) resulted in a
      synergistic increase in caspase-3 cleavage and apoptosis. These events were
      associated with the downregulation of BCR-ABL and Mcl-1, and a marked reduction
      in SPK1 expression. In imatinib mesylate-resistant K562 cells that displayed
      decreased BCR-ABL expression, bortezomib/SKI treatment markedly increased
      apoptosis and inhibited colony-formation in association with the downregulation
      of Mcl-1. Finally, the bortezomib/SKI regimen also potently induced the
      downregulation of BCR/ABL and Mcl-1 in human leukemia cells. Collectively, these
      findings suggest that combining SKI and bortezomib may represent a novel strategy
      in leukemia, including apoptosis-resistant BCR-ABL(+) hematologic malignancies.

PMID- 21195057
TI  - Adiponectin inhibits lymphotoxin-beta receptor-mediated NF-kappaB signaling in
      human umbilical vein endothelial cells.
AB  - Adiponectin exerts anti-diabetic and anti-atherogenesis properties through its 2
      receptors (AdipoR1 and AdipoR2). However, the signaling pathways responsible for
      the anti-inflammatory effects of adiponectin are largely unknown. In this study,
      we identified the lymphotoxin (LT)-beta receptor (LTBR) as an interacting partner
      of human AdipoR1 by using a yeast two-hybrid screening. The interaction between
      LTBR and AdipoR1 was confirmed by co-immunoprecipitation and co-localization
      analysis. Furthermore, adiponectin incubation inhibited lymphotoxin-induced NF
      kappaB activation and the expression of adhesion molecules in human umbilical
      vein endothelial cells. These results indicated that AdipoR1 interacted with LTBR
      and mediated the inhibition of LTBR-activated NF-kappaB pathway.

PMID- 21195058
TI  - Ferric ions inhibit proteolytic processing of progastrin.
AB  - The gastrointestinal hormone gastrin is generated from an 80 amino acid precursor
      (progastrin) by cleavage after dibasic residues by prohormone convertase 1.
      Phosphorylation of Ser(75) has previously been suggested, on the basis of
      indirect evidence, to inhibit cleavage of progastrin after Arg(73)Arg(74).
      Gastrins bind two ferric ions with high affinity, and iron binding is essential
      for the biological activity of non-amidated gastrins in vitro and in vivo. This
      study directly investigated the effect of iron binding and of serine
      phosphorylation on the cleavage of synthetic progastrin-derived peptides. The
      affinity of synthetic progastrin(55-80) for ferric ions, and the rate of cleavage
      by prohormone convertase 1, were not affected by phosphorylation of Ser(75). In
      contrast, in the presence of ferric ions the rate of cleavage of both
      progastrin(55-80) and phosphoSer(75)progastrin(55-80) by prohormone convertase 1
      was significantly reduced. Hence iron binding to progastrin may regulate
      processing and secretion in vivo, and regulation may be particularly important in
      diseases with altered iron homeostasis.

PMID- 21195059
TI  - IGFBP3 and BAG1 enhance radiation-induced apoptosis in squamous esophageal cancer
      cells.
AB  - Identification of reliable markers of radiosensitivity and the key molecules that
      enhance the susceptibility of esophageal cancer cells to anticancer treatments
      would be highly desirable. To identify molecules that confer radiosensitivity to
      esophageal squamous carcinoma cells, we assessed the radiosensitivities of the TE
      5, TE-9 and TE-12 cloneA1 cell lines. TE-12 cloneA1 cells showed significantly
      greater susceptibility to radiotherapy at 5 and 10Gy than either TE-5 or TE-9
      cells. Consistent with that finding, 24h after irradiation (5Gy), TE-12 cloneA1
      cells showed higher levels of caspase 3/7 activity than TE-5 or TE-9 cells. When
      we used DNA microarrays to compare the gene expression profiles of TE-5 and TE-12
      cloneA1 cells, we found that the mRNA and protein expression of insulin-like
      growth factor binding protein 3 (IGFBP3) and Bcl-2-associated athanogene 1 (BAG1)
      was five or more times higher in TE-12 cloneA1 cells than TE-5 cells. Conversely,
      knocking down expression of IGFBP3 and BAG1 mRNA in TE-12 cloneA1 cells using
      small interfering RNA (siRNA) significantly reduced radiosensitivity. These data
      suggest that IGFBP3 and BAG1 may be key markers of radiosensitivity that enhance
      the susceptibility of squamous cell esophageal cancer to radiotherapy. IGFBP3 and
      BAG1 may thus be useful targets for improved and more individualized treatments
      for patients with esophageal squamous cell carcinoma.

PMID- 21195061
TI  - Etiological role of cigarette smoking in rheumatoid arthritis: Nasal exposure to
      cigarette smoke condensate extracts augments the development of collagen-induced
      arthritis in mice.
AB  - Cigarette smoking is a major environmental risk factor for rheumatoid arthritis
      (RA). However, the experimental bases supporting the etiological role of
      cigarette smoking in RA have not been fully provided. We have reported that
      cigarette smoke condensate (CSC), by means of subcutaneous injection into DBA/1J
      mice with collagen and complete Freund's adjuvant or intraperitoneal injection
      one day before immunization, augmented the development of arthritis in the mouse
      model of collagen type II-induced arthritis (CIA). However, these experimental
      procedures may not be appropriate for cigarette smoking. In this study, we
      nasally exposed mice to mainstream CSC and found that CSC augmented the induction
      and development of arthritis and antibody level against collagen. Histological
      examination confirmed the augmenting effect of CSC. These findings provide
      experimental bases supporting the etiological role of cigarette smoking in RA.

PMID- 21195060
TI  - Detection of ER stress in vivo by Raman spectroscopy.
AB  - The endoplasmic reticulum (ER) is an organelle in which most membrane and
      secretory proteins are synthesized. If these proteins are not folded correctly,
      unfolded proteins accumulate in the ER lumen, causing a cellular situation known
      as ER stress. Recently, many studies on the relationship between ER stress and
      diseases have been reported. Thus, studies of ER stress in vivo should yield
      information that is useful in pathology. Model mice have been developed as a
      powerful tool to visualize ER stress in vivo, but this approach depends on
      transgenic technology. Here, we report on a method of detecting ER stress in vivo
      by Raman spectroscopy. Our experiments revealed that two specific Raman bands
      were reduced in both cultured cells and animal tissues in an ER stress dependent
      manner. This suggests that Raman spectroscopy could be a useful tool to detect ER
      stress in vivo without transgenic technology.

PMID- 21195062
TI  - CSC counteracts l-DOPA-induced overactivity of the corticostriatal synaptic
      ultrastructure and function in 6-OHDA-lesioned rats.
AB  - l-DOPA remains the gold-standard treatment for Parkinson's disease (PD). However,
      the emergence of l-DOPA-induced dyskinesia (LID) and motor fluctuations
      represents a major clinical problem in PD. The selective localization of
      adenosine A(2A) receptors to the basal ganglia and specifically to the indirect
      output pathway appear to be crucial both in the pathogenesis of PD and in the
      development of LID. In this study, we investigated the effects of a 3-week
      treatment with l-DOPA (50mg/kg/day+benserazide 12.5mg/kg/day, twice daily, i.p.)
      alone or combined with adenosine A(2A) receptor antagonist 8-(3
      Chlorostyryl)caffeine (CSC) (5mg/kg/day, twice daily), on the rotational motor
      response duration, abnormal involuntary movements (AIM) and the associated
      striatal expression of adenosine A(2A) receptor in rats with a nigrostriatal
      lesion. CSC treatment ameliorated the shortening of the rotational motor response
      duration, partly attenuated dyskinesia and reduced striatal expression of
      adenosine A(2A) receptor induced by l-DOPA. Electron microscopy technique results
      showed that the postsynapse density depth was much thicker, synapse cleft width
      was narrower and the ratio of perforated synapses significantly increased in the
      l-DOPA-treated rats, while systemic coadministration of CSC with l-DOPA
      attenuated the overactivity of corticostriatal synaptic ultrastructure and
      function induced by l-DOPA. In conclusion, CSC by means of its dual action as
      A(2A) receptor antagonist and MAO-B inhibitor ameliorated the changed behavior,
      expression of adenosine A(2A) receptor and postsynaptic effects, observed in the
      6-OHDA-lesioned rats, pointing out to its potential benefit for the treatment of
      LID.

PMID- 21195063
TI  - Olfactory marker protein expression in the vomeronasal neuroepithelium of
      tamarins (Saguinus spp).
AB  - Knowledge of the vomeronasal neuroepithelium (VNNE) microanatomy is
      disproportionately based on rodents. To broaden our knowledge, we examined
      olfactory marker protein (OMP) expression in a sample of twenty-three non-human
      primates. The density of OMP (+) vomeronasal sensory neurons (VSNs) in the VNNE
      was measured. Here we compared OMP (+) VSN density in five species of Saguinus (a
      genus of New World monkey) of different ages to a comparative primate sample that
      included representatives of every superfamily in which a VNO is postnatally
      present. In Saguinus spp., the VNNE at birth is thin, usually comprising one or
      two nuclear rows. At all ages studied, few VNNE cells are OMP reactive as view in
      coronal sections. In the comparative sample, the OMP (+) VSNs appear to be far
      more numerous in the spider monkey (another New World monkey) and the bushbaby (a
      distant relative). Other species (e.g., owl monkey) had a similar low density of
      OMP (+) VSNs as in Saguinus. These results expand our earlier finding that few
      VSNs are OMP (+) in Saguinus geoffroyi to other species of the genus. Our sample
      indicates that the number of OMP (+) VSNs in primates varies from ubiquitous to
      few with New World monkeys varying the most. The scarcity of OMP (+) cells in
      some primate VNOs reflects a lower number of terminally differentiated VSNs
      compared to a diverse range of mammals. If primates with relatively few OMP (+)
      VSNs have a functional vomeronasal system, OMP is not critical for stimulus
      detection.

PMID- 21195064
TI  - Ultrastructural GABA immunocytochemistry in the mossy fiber terminals of Wistar
      and genetic absence epileptic rats receiving amygdaloid kindling stimulations.
AB  - The existence of absence epilepsy and temporal lobe epilepsy in the same patient
      is not common in clinical practice. The reason why both types of seizures are
      rarely seen in the same patient is not well understood. Therefore, we aimed to
      investigate kindling in a well known model of human absence epilepsy, genetic
      absence epilepsy rats from Strasbourg (GAERS). In the present study, we analyzed
      whether the GABA content of GAERS that received kindling stimulations was altered
      in the hippocampal mossy fiber terminals compared to non-epileptic control (NEC)
      Wistar rats. For this purpose, we used an immunocytochemical technique at the
      ultrastructural level. Ultrathin sections were immunolabeled with anti-GABA
      antibody and transmission electron microscopy was used for the ultrastructural
      examination. The number of gold particles per nerve terminal was counted and the
      area of the nerve terminal was determined using NIH image analysis program. The
      GABA density was found to be higher in sham-operated GAERS than sham-operated
      Wistar rats. The density was increased in kindling Wistar group compared to sham
      operated Wistar and kindling GAERS groups. No statistical difference was observed
      between sham-operated GAERS and kindling GAERS groups. The increase in GABA
      levels in stimulated Wistar rats may be a result of a protective mechanism.
      Furthermore, there may be strain differences between Wistar rats and GAERS and
      our findings addressing different epileptogenesis mechanisms in these strains
      might be a basis for future experimental studies.

PMID- 21195065
TI  - Alpha-lipoic acid rebalances redox and immune-testicular milieu in septic rats.
AB  - In the present study, lipopolysaccharide (LPS), as an immune modulator in male
      adult rats and alpha-lipoic acid (ALA), as a powerful biological antioxidant and
      anti-inflammatory, are examined to help understanding the role of the immune and
      redox perturbation in testicular dysfunction with a possible protection. A total
      of 60 male Swiss albino rats were divided into 5 groups (10/group) respectively
      as follows Saline, ALA-vehicle, ALA (200mg/kg), LPS (5mg/kg) started with 20 rats
      and LPS+ALA. Obtained data from previously reported study, in our laboratory, and
      from the present one revealed that LPS induced marked reductions in sperm's
      count, motility and resulted in deterioration of the testicular histological
      features. In addition, LPS decreased testicular reduced glutathione (GSH) level
      and lactate dehydrogenase isoenzyme-x (LDH-x) activity. However, it increased
      testicular levels of malondialdehyde (MDA), nitric oxide (NO) and 8
      hydroxydeoxyguanosine (8-HDG) in testicular DNA, along with increased serum IL-2
      level. In contrast, rats pretreated with ALA showed almost complete normalization
      of all the tested parameters. In conclusion, LPS induced perturbation of the
      immune-testicular barrier as a result of redox imbalance with a subsequent
      testicular dysfunction. Pretreatment with ALA ameliorated all these effects by
      its immune-modulator and antioxidant mechanisms suggesting a protective role
      against male infertility in septic or severely infected patients.

PMID- 21195066
TI  - Crystallographic evidence for active-site dynamics in the hydrolytic aldehyde
      dehydrogenases. Implications for the deacylation step of the catalyzed reaction.
AB  - The overall chemical mechanism of the reaction catalyzed by the hydrolytic
      aldehyde dehydrogenases (ALDHs) involves three main steps: (1) nucleophilic
      attack of the thiol group of the catalytic cysteine on the carbonyl carbon of the
      aldehyde substrate; (2) hydride transfer from the tetrahedral thiohemiacetal
      intermediate to the pyridine ring of NAD(P)(+); and (3) hydrolysis of the
      resulting thioester intermediate (deacylation). Crystal structures of different
      ALDHs from several organisms-determined in the absence and presence of bound
      NAD(P)(+), NAD(P)H, aldehydes, or acid products-showed specific details at the
      atomic level about the catalytic residues involved in each of the catalytic
      steps. These structures also showed the conformational flexibility of the
      nicotinamide half of the cofactor, and of the catalytic cysteinyl and glutamyl
      residues, the latter being the general base that activates the hydrolytic water
      molecule in the deacylation step. The architecture of the ALDH active site allows
      for this conformational flexibility, which, undoubtedly, is crucial for catalysis
      in these enzymes. Focusing in the deacylation step of the ALDH-catalyzed
      reaction, here we review and systematize the crystallographic evidence of the
      structural features responsible for the conformational flexibility of the
      catalytic glutamyl residue, and for the positioning of the hydrolytic water
      molecule inside the ALDH active site. Based on the analysis of the available
      crystallographic data and of energy-minimized models of the thioester reaction
      intermediate, as well as on the results of theoretical calculations of the pK(a)
      of the carboxyl group of the catalytic glutamic acid in its three different
      conformations, we discuss the role that the conformational flexibility of this
      residue plays in the activation of the hydrolytic water. We also propose a
      critical participation in the water activation process of the peptide bond to
      which the catalytic glutamic acid in the intermediate conformation is hydrogen
      bonded.

PMID- 21195067
TI  - Spontaneous insertion of lipopolysaccharide into lipid membranes from aqueous
      solution.
AB  - Lipopolysaccharide (LPS), one of the main components of outer membranes of Gram
      negative bacteria, consists of a hydrophobic lipid (lipid A) with six hydrocarbon
      chains and a large hydrophilic polysaccharide chain. LPS plays endotoxic roles
      and can stimulate macrophages and B cells. To elucidate the mechanism of the
      interaction of LPS with various cell membranes, it is important to investigate
      the interaction of wild type LPS in a buffer with lipid membranes. In this report
      we investigated the interaction of low concentrations of LPS in a buffer with
      giant unilamellar vesicles (GUVs) of dioleoylphosphatidylcholine (DOPC) membrane
      in the liquid-crystalline (L(alpha)) phase and sphingomyelin
      (SM)/cholesterol(chol) (molar ration; 6/4) membrane in the liquid-ordered (lo)
      phase. We found that low concentrations (less than critical micelle
      concentration) of LPS in aqueous solution induced the shape changes such as the
      transformation from a prolate to a two-spheres-connected by a very narrow neck in
      the DOPC-GUVs and also in the SM/chol (6/4)-GUVs above their threshold
      concentrations. The analysis of the shape changes of the GUVs indicates that the
      monomers of LPS can insert spontaneously into the external monolayer of the lipid
      membranes of these GUVs from the aqueous solution. Moreover, higher
      concentrations of LPS induced the vesicle fission of SM/chol(6/4)-GUVs above its
      higher threshold concentration. The vesicle fission of GUVs is similar to those
      induced by single long chain amphiphiles such as lysophosphatidylcholine. On the
      basis of these results, we discuss the interaction of wild type LPS with lipid
      membranes and cell membranes. These results suggest that LPS molecules can insert
      spontaneously into the external monolayer of the plasma membranes composed of the
      L(alpha) phase-membrane and the microdomain in the lo phase.

PMID- 21195068
TI  - Discrimination between the regioisomeric 1,2- and 1,3
      diacylglycerophosphocholines by phospholipases.
AB  - The artificial 1,3-diacyl-glycero-2-phosphocholines (1,3-PCs), which form similar
      aggregate structures as the naturally occurring 1,2-diacyl-sn-glycero-3
      phosphocholines (1,2-PCs), were tested as substrates for different classes of
      phospholipases such as phospholipase A(2) (PLA(2)) from porcine pancreas, bee and
      snake venom, and Arabidopsis thaliana, phospholipase C (PLC) from Bacillus
      cereus, and phospholipase D (PLD) from cabbage and Streptomyces species. The
      regioisomers of the natural phospholipids were shown to bind to all investigated
      phospholipases with an affinity similar to the corresponding naturally occurring
      phospholipids, however their hydrolysis was reduced to different degrees (PLA(2)s
      and PLC) or even abolished (PLDs belonging to the PLD superfamily). The results
      are in accordance with binding models obtained by docking the substrates to the
      crystal structures or homology models of the phospholipases.

PMID- 21195069
TI  - SCF(TrCP) acts in endosomal sorting of the GH receptor.
AB  - The ubiquitin ligase SCF(TrCP) is required for internalisation of the growth
      hormone receptor (GHR) and acts via a direct interaction with the ubiquitin
      dependent endocytosis motif. Details of how the ligase communicates its
      information to the clathrin-mediated internalisation machinery are unknown. For
      the EGF receptor, c-Cbl acts both at the cell surface and in endosomes. We
      hypothesised that SCF(TrCP) is required for GHR degradation at both sites. This
      was tested by truncating GHR after a di-leucine-based internalisation motif
      (GHR349). This receptor enters the cells via the adapter complex AP2. We show
      that TrCP acts in an early stage of cargo selection: both TrCP silencing and
      mutation of the ubiquitin-dependent endocytosis motif force the GHR to recycle
      between endosomes and the plasma membrane, together with the transferrin
      receptor. Depletion of Tsg101 (ESCRT-I) has the same effect, while silencing of
      Hrs (ESCRT-0) prevents GH recycling. GH passes through late endosomal vesicles,
      marked by Lamp1. Coexpressing GHR and EGFR demonstrates that both receptors use
      the same route to the lysosomes. We show for the first time that SCF(TrCP) is
      involved in cargo-specific sorting at endosomes and that Tsg101 rather than Hrs
      might direct the cargo into the ESCRT machinery.

PMID- 21195070
TI  - A re-assessment of a combinatorial treatment involving Schwann cell transplants
      and elevation of cyclic AMP on recovery of motor function following thoracic
      spinal cord injury in rats.
AB  - This study was undertaken as part of the NIH "Facilities of Research-Spinal Cord
      Injury" project to support independent replication of published studies. Here, we
      repeated a study reporting that a combinatorial treatment with transplants of
      Schwann cells, systemic delivery of Rolipram to enhance cyclic AMP levels, and
      intra-spinal injections of dibutyryl cyclic AMP enhanced locomotor recovery in
      rats after contusion injuries at the thoracic level. We compared the following
      experimental groups: 1) rats that received Schwann cell transplants, systemic
      Rolipram, and injections of db-cyclic AMP (the combined treatment group that
      showed the greatest improvement in function); 2) rats that received Schwann cell
      transplants only and implantation of empty pumps as control; 3) rats that
      received Rolipram only and implantation of empty pumps as control, and 4) control
      rats that received no treatment other than the injection of DMEM into the spinal
      cord and implantation of empty pumps. The principal findings reported in Pearse
      et al. were not replicated in that the combined treatment group did not exhibit
      greater recovery on any of the measures, although the group that received Schwann
      cells only did exhibit enhanced recovery on several of the outcome measures. The
      failure of the combined treatment may be due in part to less successful
      engraftment of Schwann cells in our study vs. Pearse et al. Issues relating to
      failures to replicate, especially when effect size is small, are discussed.

PMID- 21195072
TI  - Endogenous neurotrophins and plasticity following spinal deafferentation.
AB  - Neurons intrinsic to the spinal cord dorsal horn receive input from various
      classes of long-distance projection systems. Two of the best known of these are
      primary afferent and descending monoaminergic axons. Together with intrinsic
      interneurons, activity in these axonal populations shapes the early part of the
      sensory experience before it is transmitted to supraspinal structures via
      ascending projection axons. Injury to dorsal roots, which contain the centrally
      projecting branches of primary afferent axons, results in their permanent
      disconnection from the spinal cord, as well as sensory dysfunction such as pain.
      In animals, experimental dorsal root injuries affecting a small number of roots
      produce dynamic behavioural changes, providing evidence for the now familiar
      concept that sensory processing at the level of the spinal cord is not hard
      wired. Changes in behaviour following rhizotomy suggest changes in spinal sensory
      circuitry, and we and others have shown that the density of spinal serotonergic
      axons as well as processes of inhibitory interneurons increases following
      rhizotomy. Intact primary afferent axons are less apt to sprout into denervated
      territory. Recent work from our group has asked (1) what is the stimulus that
      induces sprouting of serotonergic (and other) axons and (2) what prevents spared
      primary afferent axons from occupying the territory of those lost to injury. This
      article will review the evidence that a single factor upregulated by dorsal root
      injury, brain-derived neurotrophic factor (BDNF), underpins both serotonergic
      sprouting and a lack of primary afferent plasticity. BDNF also differentially
      modulates some of the behavioural consequences of dorsal root injury:
      antagonizing endogenous BDNF improves spontaneous mechanosensory recovery but
      prevents recovery from rhizotomy-induced hypersensitivity to cold. These findings
      reinforce the notion that in disease states as complex and variable as spinal
      cord injury, single pharmacological interventions are unlikely to produce
      meaningful results. However, understanding the differences in capacity for
      plasticity among different systems, as well as their triggers, should allow for
      more patient-tailored therapies.

PMID- 21195071
TI  - Mullerian inhibiting substance is anterogradely transported and does not
      attenuate avulsion-induced death of hypoglossal motor neurons.
AB  - Mullerian Inhibiting Substance (MIS, Anti-Mullerian hormone) is a gonadal hormone
      that contributes to the subtle sex-biases in the nervous system. Mature neurons
      of both sexes also produce MIS, suggesting that MIS may be a paracrine regulator
      of adult neural networks. We report here that murine hypoglossal motor neurons
      produce MIS and its receptors, MISRII and bone morphogenetic protein receptor 1A
      (BMPR1A, ALK3), but differentially transport them, with only MIS being detectable
      in axons. The production of MIS and its receptors were rapidly down regulated
      after axonal damage, which is a characteristic of genes involved in mature
      neuronal function. MIS is a survival factor for embryonic spinal motor neurons,
      but the rate of cell loss after hypoglossal nerve avulsion was normal in Mis(-/-)
      mice and was not attenuated by intraventricular administration of MIS. These
      observations suggest that MIS may be involved in anterograde rather than
      autocrine or retrograde regulation of neurons.

PMID- 21195073
TI  - Female sexual arousal: genital anatomy and orgasm in intercourse.
AB  - In men and women sexual arousal culminates in orgasm, with female orgasm solely
      from sexual intercourse often regarded as a unique feature of human sexuality.
      However, orgasm from sexual intercourse occurs more reliably in men than in
      women, likely reflecting the different types of physical stimulation men and
      women require for orgasm. In men, orgasms are under strong selective pressure as
      orgasms are coupled with ejaculation and thus contribute to male reproductive
      success. By contrast, women's orgasms in intercourse are highly variable and are
      under little selective pressure as they are not a reproductive necessity. The
      proximal mechanisms producing variability in women's orgasms are little
      understood. In 1924 Marie Bonaparte proposed that a shorter distance between a
      woman's clitoris and her urethral meatus (CUMD) increased her likelihood of
      experiencing orgasm in intercourse. She based this on her published data that
      were never statistically analyzed. In 1940 Landis and colleagues published
      similar data suggesting the same relationship, but these data too were never
      fully analyzed. We analyzed raw data from these two studies and found that both
      demonstrate a strong inverse relationship between CUMD and orgasm during
      intercourse. Unresolved is whether this increased likelihood of orgasm with
      shorter CUMD reflects increased penile-clitoral contact during sexual intercourse
      or increased penile stimulation of internal aspects of the clitoris. CUMD likely
      reflects prenatal androgen exposure, with higher androgen levels producing larger
      distances. Thus these results suggest that women exposed to lower levels of
      prenatal androgens are more likely to experience orgasm during sexual
      intercourse.

PMID- 21195074
TI  - The role of salivary cortisol and DHEA-S in response to sexual, humorous, and
      anxiety-inducing stimuli.
AB  - Stress and anxiety are commonly thought to be detrimental to sexual function.
      Several studies in both the human and animal literature, however, have found that
      inducing anxiety can enhance sexual function in women. The mechanisms that
      explain a negative relationship between physical and psychological stress and
      sexual functioning are well documented, but little is known about how stress or
      anxiety might have a facilitatory effect on sexual arousal. As an initial step in
      exploring the relationship between anxiety and sexual arousal, the present study
      examined the role of the autonomic nervous system, and the adrenal hormones
      cortisol and dehydroepiandrosterone-sulfate (DHEA-S) in response to a sexual
      film, an anxiety-inducing film, and a humorous film. Nineteen premenopausal women
      (mean age 24.4 years) who were free from sexual difficulties came into the lab on
      three separate days. At each session they were shown an anxiety-inducing,
      sexually arousing, or humorous (control) film while their physiological arousal
      was measured. They also provided saliva samples before and after each film.
      Cortisol significantly decreased, while DHEA-S increased in the sexual and
      humorous conditions. Neither hormone changed significantly in the anxiety
      inducing condition. Autonomic nervous system activity measured by heart rate and
      heart rate variability did not change in response to the sexual or anxiety
      inducing films, but heart rate variability increased significantly in response to
      the humorous film. The cortisol/DHEA-S ratio at the post-sexual film time point
      was significantly negatively correlated with genital arousal (measured by vaginal
      pulse amplitude). Anxiety-inducing films did not result in a physiological stress
      response, which can explain why they do not impair sexual function.

PMID- 21195075
TI  - Activity of novel nicotinic anthelmintics in cut preparations of Caenorhabditis
      elegans.
AB  - The free-living nematode Caenorhabditis elegans is a useful model for studying
      the pharmacology of anthelmintics. Currently approved anthelmintics have various
      mechanisms of action, including activity at nematode nicotinic acetylcholine
      receptors (nAChRs). Classical anthelmintic agonists of these receptors (nicotine,
      levamisole, pyrantel and bephenium) caused intact specimens of C. elegans to
      undergo contracted paralysis. The nAChR antagonist mecamylamine paralysed intact
      worms and blocked the actions of the agonists. The time to onset of effects of
      these drugs was enhanced when worms bisected between the mid- and anterior
      portions were tested. The novel anthelmintic nAChR antagonist derquantel (2
      desoxoparaherquamide, 2-DOPH) was weakly active in intact specimens of C. elegans
      at concentrations of 50 MUM over several days. No antagonism of the nAChR
      agonists was observed with this drug in intact worms. However, derquantel had
      direct and marked effects on motility in cut worms and blocked the effects of
      nAChR agonists in this preparation. A representative of the new amino
      acetonitrile derivative (AAD) class of nAChR agonists was not antagonised by
      derquantel in cut C. elegans, suggesting that these two anthelmintics may not
      demonstrate unfavourable drug-drug interactions at the receptor level if used to
      treat livestock infected with parasitic nematodes. The permeability properties of
      the C. elegans cuticle may be more restrictive than those of adult parasites,
      calling into question primary anthelmintic screening strategies that rely on this
      model organism.

PMID- 21195076
TI  - Evaluation of the reliability, validity and practicality of 3 measures of acute
      pain in infants undergoing immunization injections.
AB  - There is a need to identify a primary measure of infant pain that can be used to
      assess pain in infants undergoing vaccine injections in order to facilitate
      vaccine outcomes research. The aim of the present study was to determine the
      reliability, validity and practicality of 3 measures of acute pain in infants;
      the Modified Behavioural Pain Scale (MBPS), Neonatal Infant Pain Scale (NIPS),
      and Face Legs Activity Cry Consolability Scale (FLACC). Five raters rated pain
      from videotapes in 120 infants aged 2-6 months undergoing vaccine injections that
      participated in a randomized controlled trial designed to compare pain responses
      between two vaccines, DPTaP-Hib vaccine and PCV vaccine. Inter-rater reliability
      coefficients for baseline and vaccine injections were all greater than 0.85.
      Cronbach's alpha ranged from 0.83 to 0.94. Construct validity was demonstrated
      for all measures by vaccine injection scores that were higher (p<0.001) than
      baseline scores and by PCV scores that were higher than DPTaP-Hib scores.
      Concurrent validity was demonstrated by bi-variate correlation coefficients that
      ranged from 0.84 to 0.92. Intra-rater reliability coefficients for scores
      obtained after a single viewing (simulating real time assessment) versus multiple
      viewings were >= 0.96. All measures demonstrated a significant difference in pain
      scores between the more painful (PCV) and less painful (DPTaP-Hib) vaccine for
      scores obtained after a single viewing. The majority of raters (4 out of 5)
      preferred the MBPS. Together, these results provide preliminary support for the
      MBPS as the primary outcome of pain during vaccine injections in infants.

PMID- 21195077
TI  - A Phase I safety study of plasmid DNA immunization targeting carcinoembryonic
      antigen in colorectal cancer patients.
AB  - A plasmid DNA vaccine, encoding a truncated form of human CEA fused to a T-helper
      epitope (CEA66 DNA) was delivered three times intradermally at 2 mg or
      intramuscularly at 8 mg by Biojector(r) to patients with colorectal cancer. Prior
      to the first vaccination, all patients received cyclophosphamide (300 mg/m2)
      intravenously. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was
      administered subcutaneously with each vaccination. All patients completed the
      vaccine schedule. There were no grade 3 or 4 adverse events (AE). The most
      frequently reported AE grades 1 and 2 were injection site reactions, fatigue,
      headache, arthralgia, chest tightness and myalgia. Vaccination with CEA66 DNA in
      combination with GM-CSF was well tolerated and no signs of autoimmunity have been
      detected.

PMID- 21195078
TI  - Enhancement of immunogenicity of a virosome-based avian influenza vaccine in
      chickens by incorporating CpG-ODN.
AB  - Influenza virosomes are virus-like particles, representing a platform for vaccine
      development. In this study, we examined the immunogenicity of avian influenza
      virosomes with or without inclusion of recombinant chicken interferon-gamma
      (rChIFN-gamma) or CpG-ODN in chickens. Immunization with virosomes adjuvanted
      with CpG-ODN elicited the highest haemagglutination inhibition antibody titres,
      as well as IgG and IgA serum antibody responses. Moreover, Virosomes+CpG-ODN
      formulation induced an antigen-specific spleen cell proliferation and IFN-gamma
      expression. In conclusion, our results demonstrated that virus-specific antibody-
      and cell-mediated responses may be induced in chickens immunized with virosomes
      and these responses can be enhanced by incorporating CpG-ODN in the virosome
      vaccine formulation.

PMID- 21195079
TI  - Vaccine protection against lethal homologous and heterologous challenge using
      recombinant AAV vectors expressing codon-optimized genes from pandemic swine
      origin influenza virus (SOIV).
AB  - The recent H1N1 influenza pandemic and the inevitable delay between
      identification of the virus and production of the specific vaccine have
      highlighted the urgent need for new generation influenza vaccines that can
      preemptively induce broad immunity to different strains of the virus. In this
      study we have produced AAV-based vectors expressing the A/Mexico/4603/2009 (H1N1)
      hemagglutinin (HA), nucleocapsid (NP) and the matrix protein M1 and have
      evaluated their ability to induce specific immune response and protect mice
      against homologous and heterologous challenge. Each of the vaccine vectors
      elicited potent cellular and humoral immune responses in mice. Although
      immunization with AAV-M1 did not improve survival after challenge with the
      homologous strain, immunization with the AAV-H1 and AAV-NP vectors resulted in
      survival of all mice, as did inoculation with a combination of all three vectors.
      Furthermore, trivalent vaccination also conferred partial protection against
      challenge with the highly heterologous and virulent A/PR/8/34 strain of H1N1
      influenza.

PMID- 21195081
TI  - Antioxidant therapy attenuates myocardial telomerase activity reduction in
      superoxide dismutase-deficient mice.
AB  - Oxidative stress plays a pathological role in the development of heart failure.
      This study examined telomere biology in heart/muscle-specific manganese
      superoxide dismutase-deficient mice (H/M-SOD2(-/-)), which develop progressive
      congestive heart failure and exhibit pathology typical of dilated cardiomyopathy.
      EUK-8 (25mg/kg/day), a superoxide dismutase and catalase mimetic, was
      administered to H/M-SOD2(-/-) mice for four weeks beginning at 8 weeks of age.
      Telomere length, telomerase activity, telomere-associated proteins, and cell
      death signals were assessed in hearts from control wild-type mice (H/M-Sod2 (lox/
      lox)) and H/M-SOD2(-/-) mice either treated or untreated with EUK-8. While
      cardiac function was unchanged in these experimental mice, the end-diastolic
      dimension in H/M-SOD2(-/-) mice was notably dilated and could be significantly
      reduced by EUK-8 treatment. At the end of the study, no shortening of telomere
      length was observed in heart tissues from all mice tested, but telomerase
      activity was decreased in heart tissue from H/M-SOD2(-/-) mice compared to
      control mice. Protein expression for telomerase reverse transcriptase and
      telomere repeat binding factor 2 was also downregulated in H/M-SOD2(-/-) heart
      tissue as was expression of phospho-Akt, insulin-like growth factor, and
      endothelial nitric oxide synthase. Expression levels of Sirt1, a lifespan
      modulator, were enhanced while FoxO3a was depressed in H/M-SOD2(-/-) hearts. All
      of the changes seen in H/M-SOD2(-/-) heart tissue could be inhibited by EUK-8
      treatment. Taken together, the results suggest that oxidant stress might affect
      myocardial telomerase activity and telomere-associated proteins. Telomerase may
      therefore play a pivotal role in antioxidant defense mechanisms, and may be
      useful as a novel therapeutic tool for treating human heart failure.

PMID- 21195080
TI  - Comparison of immune responses generated by optimized DNA vaccination against SIV
      antigens in mice and macaques.
AB  - Optimized DNA vectors were constructed comprising the proteome of SIV including
      the structural, enzymatic, regulatory, and accessory proteins. In addition to
      native antigens as produced by the virus, fusion proteins and modified antigens
      with altered secretion, cellular localization and stability characteristics were
      generated. The DNA vectors were tested for expression upon transfection in human
      cells. In addition, the vectors were tested either alone or in combinations in
      mice and macaques, which provided an opportunity to compare immune responses in
      two animal models. DNA only immunization using intramuscular injection in the
      absence or presence of in vivo electroporation did not alter the phenotype of the
      induced T cell responses in mice. Although several fusion proteins induced immune
      responses to all the components of a polyprotein, we noted fusion proteins that
      abrogated immune response to some of the components. Since the expression levels
      of such fusion proteins were not affected, these data suggest that the immune
      recognition of certain components was altered by the fusion. Testing different
      DNA vectors in mice and macaques revealed that a combination of DNAs producing
      different forms of the same antigen generated more balanced immune responses, a
      desirable feature for an optimal AIDS vaccine.

PMID- 21195082
TI  - Regulation of Abro1/KIAA0157 during myocardial infarction and cell death reveals
      a novel cardioprotective mechanism for Lys63-specific deubiquitination.
AB  - Abro1 (also known as KIAA0157) is a scaffold protein that recruits polypeptides
      to assemble the BRISC (BRCC36-containing isopeptidase complex) deubiquitinating
      (DUB) enzyme. The four subunits of BRISC enzyme include Abro1, NBA1, BRE, and
      BRCC36 proteins. The DUB activity of the BRISC enzyme is exclusively directed
      against Lys63-linked polyubiquitin that does not have a proteolytic role but
      regulates protein function. In this report, we identified Abro1 as a specific
      interactor of THAP5, a zinc finger transcription factor that is involved in G2/M
      control and apoptosis. Abro1 was predominantly expressed in the heart and its
      protein level was regulated following experimentally induced myocardial
      ischemia/reperfusion (MI/R) injury. Furthermore, in patients with coronary artery
      disease (CAD), there was a dramatic increase in Abro1 protein level in the
      myocardial infarction (MI) area. Increase in Abro1 leads to a significant
      reduction in Lys63-linked ubiquitination of specific protein targets. Reducing
      the Abro1 protein level exacerbated cellular damage and cell death of
      cardiomyocytes due to MI/R injury. Additionally, overexpression of Abro1 in a
      heterologous system provided significant protection against oxidative stress
      induced apoptosis. In conclusion, our results demonstrate that Abro1 protein
      level substantially increases in myocardial injury and coronary artery disease
      and this up-regulation is part of a novel cardioprotective mechanism. In
      addition, our data suggest a potential new link between Lys63-specific
      ubiquitination, its modulation by the BRISC DUB enzyme, and the development and
      progression of heart disease.

PMID- 21195083
TI  - Glycosylation-independent binding to extracellular domains 11-13 of mannose-6
      phosphate/insulin-like growth factor-2 receptor mediates the effects of soluble
      CREG on the phenotypic modulation of vascular smooth muscle cells.
AB  - The bio-effects of cellular repressor of E1A-stimulated genes (CREG) have been
      proposed to depend on its N-glycosylation and binding to mannose-6
      phosphate/insulin-like growth factor-2 receptor (M6P/IGF2R). The present study
      aimed to investigate the detailed mode and specific sites for their binding and
      the functional relevance of this binding in the phenotypic modulation of vascular
      smooth muscle cells (SMCs). Wild-type and glycosylation mutant human CREG (wtCREG
      and mCREG) proteins were expressed and isolated from HEK293 cells. CREG knocked
      down SMCs were used to evaluate their biological activity. Both wtCREG and mCREG
      arrest cell cycle progression of CREG knocked-down SMCs when added to the culture
      medium. In vitro binding assay revealed that CREG bound to M6P/IGF2R
      extracellular domains 7-10 and 11-13 in a glycosylation-dependent and 
      independent manner, respectively. Further blocking experiments using soluble
      M6P/IGF2R fragments and M6P/IGF2R neutralizing antibody suggest that the binding
      to domains 11-13, as well as to 7-10, is adequate for CREG to modulate SMC
      proliferation. These data suggest that soluble CREG protein can exert its
      biological function via glycosylation-independent binding to the extracellular
      domains 11-13 of cell surface M6P/IGF2R, and thereby provide novel insights into
      CREG modulation of SMC phenotypic switching from contractile to proliferative.

PMID- 21195085
TI  - MCM3AP is transcribed from a promoter within an intron of the overlapping gene
      for GANP.
AB  - MCM3 acetylase (MCM3AP) and germinal-centre associated nuclear protein (GANP) are
      transcribed from the same locus and are therefore confused in databases because
      the MCM3 acetylase DNA sequence is contained entirely within the much larger GANP
      sequence and the entire MCM3AP sequence is identical to the carboxy terminus of
      GANP. Thus, the MCM3AP and GANP genes are read in the same reading frame and
      MCM3AP is an N-terminally truncated region of GANP. However, we show here that
      MCM3AP and GANP are different proteins, occupying different locations in the cell
      and transcribed from different promoters. Intriguingly, a promoter for MCM3AP
      lies within an intron of GANP. This report is an interesting example in nature of
      two separate gene products from the same locus that perform two entirely
      different functions in the cell. Therefore, to avoid further confusion, they
      should now be referred to as separate but overlapping genes.

PMID- 21195084
TI  - SERCA2a controls the mode of agonist-induced intracellular Ca2+ signal,
      transcription factor NFAT and proliferation in human vascular smooth muscle
      cells.
AB  - In blood vessels, tone is maintained by agonist-induced cytosolic Ca(2+)
      oscillations of quiescent/contractile vascular smooth muscle cells (VSMCs).
      However, in synthetic/proliferative VSMCs, Gq/phosphoinositide receptor-coupled
      agonists trigger a steady-state increase in cytosolic Ca(2+) followed by a Store
      Operated Calcium Entry (SOCE) which translates into activation of the
      proliferation-associated transcription factor NFAT. Here, we report that in human
      coronary artery smooth muscle cells (hCASMCs), the sarco/endoplasmic reticulum
      calcium ATPase type 2a (SERCA2a) expressed in the contractile form of the
      hCASMCs, controls the nature of the agonist-induced Ca(2+) transient and the
      resulting down-stream signaling pathway. Indeed, restoring SERCA2a expression by
      gene transfer in synthetic hCASMCs 1) increased Ca(2+) storage capacity; 2)
      modified agonist-induced IP(3)R Ca(2+) release from steady-state to oscillatory
      mode (the frequency of agonist-induced IP(3)R Ca(2+) signal was 11.66 +/-
      1.40/100 s in SERCA2a-expressing cells (n=39) vs 1.37 +/- 0.20/100 s in control
      cells (n=45), p<0.01); 3) suppressed SOCE by preventing interactions between SR
      calcium sensor STIM1 and pore forming unit ORAI1; 4) inhibited calcium regulated
      transcription factor NFAT and its down-stream physiological function such as
      proliferation and migration. This study provides evidence for the first time that
      oscillatory and steady-state patterns of Ca(2+) transients have different effects
      on calcium-dependent physiological functions in smooth muscle cells.

PMID- 21195087
TI  - M13 procoat protein insertion into YidC and SecYEG proteoliposomes and liposomes.
AB  - M13 procoat protein was one of the first model proteins used to study bacterial
      membrane protein insertion. It contains a signal peptide of 23 amino acid
      residues and is not membrane targeted by the signal recognition particle. The
      translocation of its periplasmic domain is independent of the preprotein
      translocase (SecAYEG) but requires electrochemical membrane potential and the
      membrane insertase YidC of Escherichia coli. We show here that YidC is sufficient
      for efficient membrane insertion of the purified M13 procoat protein into
      energized YidC proteoliposomes. When no membrane potential is applied, the
      insertion is substantially reduced. Only in the presence of YidC, membrane
      insertion occurs if bilayer integrity is preserved and membrane potential is
      stable for more than 20 min. A mutant of the M13 procoat protein, H5EE, with two
      additional negatively charged residues in the periplasmic domain inserted into
      YidC proteoliposomes and SecYEG proteoliposomes with equal efficiencies. We
      conclude that the protein can use both the YidC-only pathway and the Sec pathway.
      This poses the questions of how procoat H5EE is inserted in vivo and how
      insertion pathways are selected in the cell.

PMID- 21195086
TI  - Inhibition of glycosaminoglycan-mediated amyloid formation by islet amyloid
      polypeptide and proIAPP processing intermediates.
AB  - Islet amyloid polypeptide (IAPP; also known as amylin) is responsible for islet
      amyloid formation in type 2 diabetes, and IAPP-induced toxicity is believed to
      contribute to the loss of beta-cell mass associated with the late stages of type
      2 diabetes. Islet amyloid formation may also play a role in graft failure after
      transplantation. IAPP is produced as a prohormone, pro-islet amyloid polypeptide
      (proIAPP), and processed in the secretory granules of the pancreatic beta-cells.
      Partially processed forms of proIAPP are found in amyloid deposits; most notable
      is a 48-residue intermediate, proIAPP(1-48), which includes the N-terminal pro
      extension, but which has been properly processed at the C-terminus. Incomplete
      processing may play a role in islet amyloid formation by promoting interactions
      with sulfated proteoglycans of the extracellular matrix, which, in turn, promote
      amyloid formation. We show that acid fuchsin (3-(1-(4-amino-3-methyl-5
      sulphonatophenyl)-1-(4-amino-3-sulphonatophenyl)methylene)cyclohexa-1,4
      dienesulphonic acid), a simple sulfonated triphenyl methyl derivative, is a
      potent inhibitor of amyloid formation by the proIAPP(1-48) intermediate. The more
      complicated triphenyl methane derivative fast green FCF {ethyl-[4-[[4-[ethyl-[(3
      sulfophenyl)methyl]amino]phenyl]-(4-hydroxy-2-sulfophenyl)methylidene]-1
      cyclohexa-2,5-dienylidene]-[(3-sulfophenyl)methyl]azanium} also inhibits amyloid
      formation by IAPP and the proIAPP processing intermediate. Both compounds inhibit
      amyloid formation by mixtures of the proIAPP intermediate and the model
      glycosaminoglycan heparan sulfate. Acid fuchsin also inhibits glycosaminoglycan
      mediated amyloid formation by mature IAPP. The ability to inhibit amyloid
      formation is not simply due to the compounds being sulfonated, since the
      sulfonated inhibitor of amyloid-beta, tramiprosate, is not an inhibitor of
      amyloid formation by proIAPP(1-48).

PMID- 21195088
TI  - The recognition specificity of the CHD1 chromodomain with modified histone H3
      peptides.
AB  - Histone tail peptides comprise the flexible portion of chromatin, the substance
      which serves as the packaging for the eukaryotic genome. According to the histone
      code hypothesis, reader protein domains (chromodomains) can recognize
      modifications of amino acid residues within these peptides, regulating the
      expression of genes. We have performed simulations on models of chromodomain
      helicase DNA-binding protein 1 complexed with a variety of histone H3
      modifications. Binding free energies for both the overall complexes and the
      individual residues within the protein and peptides were computed with molecular
      mechanics-generalized Born surface area. The simulation results agree well with
      experimental data and identify several chromodomain helicase DNA-binding protein
      1 residues that play key roles in the interaction with each of the H3
      modifications. We identified one class of protein residues that bind to H3 in all
      of the complexes (generally interacting hydrophobically), and a second class of
      residues that bind only to particular H3 modifications (generally interacting
      electrostatically). Additionally, we found that modifications of H3R2 and H3T3
      have a dominant effect on the binding affinity; methylation of H3K4 has little
      effect on the interaction strength when H3R2 or H3T3 is modified. Our findings
      with regard to the specificity shown by the latter class of protein residues in
      their binding affinity to certain modifications of H3 support the histone code
      hypothesis.

PMID- 21195089
TI  - Structure of hibiscus latent singapore virus by fiber diffraction: a nonconserved
      his122 contributes to coat protein stability.
AB  - Hibiscus latent Singapore virus (HLSV) is a rigid rod-shaped plant virus and a
      new member of the Tobamovirus family. Unlike all other Tobamoviruses, the HLSV
      genome contains a unique poly(A) tract in its 3' untranslated region. The virion
      is composed of a monomeric coat protein (CP) unit of 18 kDa, arranged as a right
      handed helix around the virus axis. We have determined the structure of HLSV at
      3.5 A by X-ray fiber diffraction and refined it to an R-factor of 0.096. While
      the overall structure of the HLSV CP resembles that of other Tobamoviruses, there
      are a few unique differences. There is a kink in the LR helix due to the presence
      of His122. Also, the adjacent Lys123 may further destabilize the helix by
      positive charge repulsion, making the kink more pronounced. The His122-Asp88 salt
      bridge provides significant stability to the loop adjacent to the RR helix.
      Carboxyl-carboxylate interactions that drive viral disassembly are also different
      in HLSV. The nucleotide recognition mechanisms for virus assembly between HLSV
      and ribgrass mosaic virus are similar, but different between tobacco mosaic virus
      and cucumber green mottle mosaic virus.

PMID- 21195090
TI  - The low conductance mitochondrial permeability transition pore confers
      excitability and CICR wave propagation in a computational model.
AB  - Mitochondria have long been known to sequester cytosolic Ca(2+) and even to shape
      intracellular patterns of endoplasmic reticulum-based Ca(2+) signaling. Evidence
      suggests that the mitochondrial network is an excitable medium which can
      demonstrate independent Ca(2+) induced Ca(2+) release via the mitochondrial
      permeability transition. The role of this excitability remains unclear, but
      mitochondrial Ca(2+) handling appears to be a crucial element in diverse diseases
      as diabetes, neurodegeneration and cardiac dysfunction that also have
      bioenergetic components. In this paper, we extend the modular Magnus-Keizer
      computational model for respiration-driven Ca(2+) handling to include a
      permeability transition based on a channel-like pore mechanism. We demonstrate
      both excitability and Ca(2+) wave propagation accompanied by depolarizations
      qualitatively similar to those reported in cell and isolated mitochondria
      preparations. These waves depend on the energy state of the mitochondria, as well
      as other elements of mitochondrial physiology. Our results support the concept
      that mitochondria can transmit state dependent signals about their function
      across the mitochondrial network. Our model provides the tools for predictions
      about the internal physiology that leads to this qualitatively different Ca(2+)
      excitability seen in mitochondria.

PMID- 21195091
TI  - The evolution of developmental timing in natural enemy systems.
AB  - Natural parasitoid systems exhibit considerable variation in their life history
      properties yet little is known about the effects of development time on
      parasitoid fitness or of the conditions that might select for rapid development
      at the expense of reduced parasitoid growth. In this study the techniques of
      adaptive dynamics are applied to a discrete time host-parasitoid model to examine
      the evolution of parasitoid life history strategies. In particular, we explore
      the conditions that select for variation in parasitoid traits, such as, the
      timing of parasitoid attack and emergence from the host. The process of
      evolutionary branching, leading to dimorphism, can occur when the benefits to
      reproduction of early parasitoid attack are bought at a cost in terms of
      mortality of late parasitoid emergence from the host. We also find that trends in
      parasitoid life history traits depend critically on the nature of the underlying
      population dynamics. Increases in the strength of host density-dependence acts to
      select for shorter parasitoid development time and lower searching efficiency
      when the underlying population dynamics are at equilibrium. This trend is
      reversed when the underlying population dynamics exhibit fluctuations. Here,
      fluctuations in host density driven by parasitism become more extreme as the
      strength of host density-dependence decreases and so the parasitoid selects early
      emergence to avoid the mortality experienced at outbreak host densities. Our
      results are consistent with the general principle that parasitoids facing high
      mortality risk favour short development times over size and high searching
      efficiency, whereas species facing low mortality risks favour size at the cost of
      increased development time.

PMID- 21195092
TI  - A theoretical application of selectable markers in bacterial episomes for a DNA
      cryptosystem.
AB  - A theoretical model utilizing the principle of selection for the purposes of DNA
      cryptography is proposed. A method to enhance the security of DNA cryptosystems
      that utilize polymerase chain reaction primer keys is presented. Double
      encryption systems--encryption systems that have two keys--like the cryptosystem
      advanced in this paper, are generally more secure than systems that have one key.
      Two problems with this model are also discussed, and a hypothetical solution to
      the most major problem is proposed. The chief advantage of this DNA cryptosystem
      over other DNA cryptosystems is that it has, in theory, two equally secure keys
      an intruder must break through in order to access a secret message. No
      experimental analysis has been conducted by the author regarding any of the
      theoretical methods proposed in this paper.

PMID- 21195093
TI  - Dynamics of a plant-herbivore-predator system with plant-toxicity.
AB  - A system of ordinary differential equations is considered that models the
      interactions of two plant species populations, an herbivore population, and a
      predator population. We use a toxin-determined functional response to describe
      the interactions between plant species and herbivores and use a Holling Type II
      functional response to model the interactions between herbivores and predators.
      In order to study how the predators impact the succession of vegetation, we
      derive invasion conditions under which a plant species can invade into an
      environment in which another plant species is co-existing with a herbivore
      population with or without a predator population. These conditions provide
      threshold quantities for several parameters that may play a key role in the
      dynamics of the system. Numerical simulations are conducted to reinforce the
      analytical results. This model can be applied to a boreal ecosystem trophic chain
      to examine the possible cascading effects of predator-control actions when plant
      species differ in their levels of toxic defense.

PMID- 21195094
TI  - Mutation frequency is not elevated in the cerebellum of harlequin/Big Blue((r))
      mice but Class II deletions occur preferentially in young harlequin cerebellum.
AB  - The harlequin (hq)/Big Blue((r)) mouse is a model of premature aging with
      neurodegeneration and a transgenic mutation target (lambdacII gene) for in vivo
      mutation analysis in individual tissues. The hq mutation results in
      downregulation of the apoptosis-inducing factor (Aif) gene with conflicting
      reports of elevated oxidative stress in neurons. Previously, the cerebellum of hq
      disease mice was reported to have a three-fold elevated frequency of -1bp
      deletions at a monobasic run (G(11)), a common mutation signature of reactive
      oxygen species [1]. To examine a diversity of mutations types associated with
      oxidative DNA damage, the frequency and nature of spontaneous cII mutations were
      determined in the cerebellum of three- and seven-month-old hq disease and Aif
      proficient Big Blue((r)) mice. Unlike the previous report, no elevation in
      spontaneous mutation frequency was observed in the cerebellum of hq disease
      compared to Aif-proficient mice. The G(11) sequence used in the previous study
      may be particularly susceptible to oxidative DNA damage leading to replication
      errors and the previous assay may detect transcriptional errors. We observed
      intrachromosomal deletions (10-21bp) associated with oxidative DNA damage
      exclusively in the cerebellum of four out of five young hq disease mice
      (p=0.0001). The pattern of mutation in the cerebellum of hq disease and Aif
      proficient mice was similar. This mutation pattern is typical of previous reports
      of spontaneous mutations across multiple tissues and ages of wild type mice.
      Finally, an Aif-proficient mouse had the heaviest mutation shower yet reported
      with seven point mutations over 21bp in a single mutant, consistent with
      transient hypermutability, a phenomenon relevant to disease and genome evolution.

PMID- 21195095
TI  - Cadmium induced radioadaptive response via an ATM-independent H(2)S/cystathionine
      gamma-lyase modulation.
AB  - The combined exposure to environmental toxicants such as heavy metals and
      radiation is an important research area in health protection. Here we explored
      cadmium induced radioadaptive response (RAR) and investigated the role of
      hydrogen sulfide (H(2)S) and ATM kinase in this response. Our data showed that
      the cadmium ions with a sub-lethal concentration could induce RAR in Chang liver
      cells towards subsequent gamma-irradiation and this response could be abrogated
      by DL-propargylglycine (PPG), the endogenous H(2)S synthetase inhibitor of
      cystathionine gamma-lyase (CSE), but not by aminooxyacetic acid (AOAA), the
      inhibitor of cystathionine beta-synthase (CBS). Moreover, the pretreatment of
      cells with NaHS also stimulated cellular adaptive response to radiation. Both
      cadmium treatment and irradiation up-regulated the expression of CSE protein in a
      time-dependent manner but had no influence on the expression of CBS protein. In
      the primed cells, the time course of CBS expression showed no significant
      difference with the cells treated with 2Gy irradiation alone, however, the CSE
      expression was easier to reach the maximum level, indicating a more efficient
      H(2)S production by CSE. Moreover, the cadmium-induced RAR was totally suppressed
      by KU-55933, a specific ATM inhibitor that did not change the CSE expression
      after radiation. However, exogenous H(2)S decreased the phosphorylation level of
      radiation-induced ATM. In conclusion, the present results demonstrate firstly
      that H(2)S is involved in the cadmium induced cross-adaptive response to
      challenging radiation. CSE, rather than CBS, may mainly responsible for the H(2)S
      production during this RAR which may also be mediated by ATM pathway. However,
      the activation of CSE is independent of ATM but could negatively regulate the
      phosphorylation of ATM.

PMID- 21195096
TI  - Different actions for acute and chronic administration of mirtazapine on
      serotonergic transmission associated with raphe nuclei and their innervation
      cortical regions.
AB  - The atypical antidepressant, mirtazapine enhances noradrenergic transmission, but
      its effects on serotonergic transmission remain to be clarified. The present
      study determined the effects of acute and chronic administration of mirtazapine
      on serotonergic transmissions in raphe nuclei and their innervation regions,
      frontal and entorhinal cortex, using multiple-probes microdialysis with real-time
      PCR and western blotting. Acute administration of mirtazapine did not affect
      extracellular serotonin level in raphe nuclei or cortex; however, chronic
      administration increased extracellular serotonin level in raphe nuclei without
      affecting that in cortex. Blockade of 5-HT1A receptor, but not that of the 5
      HT2A/2C receptor, enhanced the effects of acute administration of mirtazapine on
      extracellular serotonin level in raphe nuclei. Chronic mirtazapine administration
      reduced the inhibitory function associated with somatodendritic 5-HT1A receptor
      in raphe nuclei, but enhanced postsynaptic 5-HT1A receptor in serotonergic
      innervated cortical regions. Chronic administration reduced the expression of
      mRNA and protein of serotonin transporter and 5-HT1A receptor in raphe nuclei,
      but not in the cortices. These results suggested that acute administration of
      mirtazapine probably activated serotonergic transmission, but its stimulatory
      action was abolished by activated inhibitory 5-HT1A receptor. Chronic
      administration of mirtazapine resulted in increased extracellular serotonin level
      via reduction of serotonin transporter with reduction of somatodendritic 5-HT1A
      autoreceptor function in raphe nuclei. These pharmacological actions of
      mirtazapine include its serotonergic profiles as noradrenergic and specific
      serotonergic antidepressant (NaSSA).

PMID- 21195097
TI  - Role of microcircuit structure and input integration in hippocampal interneuron
      recruitment and plasticity.
AB  - The proper operation of cortical neuronal networks depends on the temporally
      precise recruitment of GABAergic inhibitory interneurons. Inhibitory cells
      receive convergent excitatory inputs from afferent pathways, as well as local
      collaterals of principal cells, and provide feedforward or feedback inhibition
      within the circuitry. Accumulating evidence indicates that recruitment of
      GABAergic cells is highly diverse among interneuron types. Differences in the
      properties of input synapses, dendritic architecture and membrane properties, as
      well as the rich repertoire of plasticity mechanisms contribute to this
      diversity. Efficient and precise recruitment of interneurons is thought to depend
      on the coincident occurrence of rapid synaptic responses and their faithful
      propagation to the action potential initiation site. However, slow inputs can
      also play important roles by facilitating the activation of interneurons by rapid
      synaptic inputs and supporting associative synaptic plasticity. Here we review
      how the diversity in the synaptic and integrative properties as well as dendritic
      geometry of hippocampal inhibitory cells impact on their activation. We further
      discuss how the various modes of interneuron recruitment can support the
      versatile cell type- and input-specific computational functions which appear to
      be adapted to the structure and the function of the network they are embedded in.
      This article is part of a Special Issue entitled 'Synaptic Plasticity &
      Interneurons'.

PMID- 21195098
TI  - Induction and expression rules of synaptic plasticity in hippocampal
      interneurons.
AB  - The knowledge that excitatory synapses on aspiny hippocampal interneurons can
      develop genuine forms of activity-dependent remodeling, independently from the
      surrounding network of principal cells, is a relatively new concept. Cumulative
      evidence has now unequivocally demonstrated that, despite the absence of
      specialized postsynaptic spines that serve as compartmentalized structure for
      intracellular signaling in principal cell plasticity, excitatory inputs onto
      interneurons can undergo forms of synaptic plasticity that are induced and
      expressed autonomously from principal cells. Yet, the rules for induction and
      expression of interneuron plasticity are much more heterogeneous than in
      principal neurons. Long-term plasticity in interneurons is not necessarily
      dependent upon postsynaptic activation of NMDA receptors nor relies on the same
      postsynaptic membrane potential requirements as principal cells. Plasticity in
      interneurons rather requires activation of Ca(2+)-permeable AMPA receptors and/or
      metabotropic glutamate receptors and is triggered by postsynaptic
      hyperpolarization. In this review we will outline these distinct features of
      interneuron plasticity and identify potential critical candidate molecules that
      might be important for sustaining long-lasting changes in synaptic strength at
      excitatory inputs onto interneurons. This article is part of a Special Issue
      entitled 'Synaptic Plasticity & Interneurons'.

PMID- 21195099
TI  - Direct inhibition of hypocretin/orexin neurons in the lateral hypothalamus by
      nociceptin/orphanin FQ blocks stress-induced analgesia in rats.
AB  - We recently demonstrated that hypocretin/orexin (Hcrt) and nociceptin/orphanin FQ
      (N/OFQ) systems coordinately regulate nociception in a mouse model of stress
      induced analgesia (SIA). However, the site of N/OFQ action on modulation of SIA
      was elusive, since N/OFQ was administered via intracerebroventricular (i.c.v.)
      injection acting on widely distributed N/OFQ receptors (NOP) in the brain. In the
      present study, we tested the hypothesis that N/OFQ modulates the SIA directly via
      the inhibition of the Hcrt neurons in the lateral hypothalamus. Using both
      fluorescent and electron microscopy, we found that N/OFQ-containing neurons are
      located in the lateral hypothalamus and the N/OFQ-containing fibers make direct
      contacts with the Hcrt neurons. Paw thermal nociceptive test revealed that the
      immobilization restraint of the rat increased the thermal pain threshold by 20.5
      +/- 7.6%. Bilateral microinjection of N/OFQ (9 MUg/side) into the rat
      perifornical area of the lateral hypothalamus, the brain area in which the Hcrt
      neurons are exclusively located, abolished the SIA. Activity of Hcrt neurons in
      the same animals was assessed using Fos immunohistochemistry. Percentage of
      Fos(+)/Hcrt neurons was lower in rats injected with N/OFQ than rats injected with
      saline, with the difference between groups stronger in the Hcrt neurons located
      medially to the fornix than in Hcrt neurons located laterally to the fornix.
      These results suggest that N/OFQ modulation of SIA is mediated by direct
      inhibition of Hcrt neuronal activity in the perifornical area. The uncovered
      peptidergic interaction circuitry may have broad implication in coordinated
      modulation by Hcrt and N/OFQ on other stress adaptive responses.

PMID- 21195100
TI  - Specific language and reading skills in school-aged children and adolescents are
      associated with prematurity after controlling for IQ.
AB  - Although studies of long-term outcomes of children born preterm consistently show
      low intelligence quotient (IQ) and visual-motor impairment, studies of their
      performance in language and reading have found inconsistent results. In this
      study, we examined which specific language and reading skills were associated
      with prematurity independent of the effects of gender, socioeconomic status
      (SES), and IQ. Participants from two study sites (N=100) included 9-16-year old
      children born before 36 weeks gestation and weighing less than 2500 grams
      (preterm group, n=65) compared to children born at 37 weeks gestation or more
      (full-term group, n=35). Children born preterm had significantly lower scores
      than full-term controls on Performance IQ, Verbal IQ, receptive and expressive
      language skills, syntactic comprehension, linguistic processing speed, verbal
      memory, decoding, and reading comprehension but not on receptive vocabulary.
      Using MANCOVA, we found that SES, IQ, and prematurity all contributed to the
      variance in scores on a set of six non-overlapping measures of language and
      reading. Simple regression analyses found that after controlling for SES and
      Performance IQ, the degree of prematurity as measured by gestational age group
      was a significant predictor of linguistic processing speed, beta=-.27, p<.05,
      R(2)=.07, verbal memory, beta=.31, p<.05, R(2)=.09, and reading comprehension,
      beta=.28, p<.05, R(2)=.08, but not of receptive vocabulary, syntactic
      comprehension, or decoding. The language and reading domains where prematurity
      had a direct effect can be classified as fluid as opposed to crystallized
      functions and should be monitored in school-aged children and adolescents born
      preterm.

PMID- 21195101
TI  - Remembering 'zeal' but not 'thing': reverse frequency effects as a consequence of
      deregulated semantic processing.
AB  - More efficient processing of high frequency (HF) words is a ubiquitous finding in
      healthy individuals, yet frequency effects are often small or absent in stroke
      aphasia. We propose that some patients fail to show the expected frequency effect
      because processing of HF words places strong demands on semantic control and
      regulation processes, counteracting the usual effect. This may occur because HF
      words appear in a wide range of linguistic contexts, each associated with
      distinct semantic information. This theory predicts that in extreme
      circumstances, patients with impaired semantic control should show an outright
      reversal of the normal frequency effect. To test this prediction, we tested two
      patients with impaired semantic control with a delayed repetition task that
      emphasised activation of semantic representations. By alternating HF and low
      frequency (LF) trials, we demonstrated a significant repetition advantage for LF
      words, principally because of perseverative errors in which patients produced the
      previous LF response in place of the HF target. These errors indicated that HF
      words were more weakly activated than LF words. We suggest that when presented
      with no contextual information, patients generate a weak and unstable pattern of
      semantic activation for HF words because information relating to many possible
      contexts and interpretations is activated. In contrast, LF words are associated
      with more stable patterns of activation because similar semantic information is
      activated whenever they are encountered.

PMID- 21195102
TI  - The influence of information structure on the depth of semantic processing: how
      focus and pitch accent determine the size of the N400 effect.
AB  - To highlight relevant information in dialogues, both wh-question context and
      pitch accent in answers can be used, such that focused information gains more
      attention and is processed more elaborately. To evaluate the relative influence
      of context and pitch accent on the depth of semantic processing, we measured
      event-related potentials (ERPs) to auditorily presented wh-question-answer pairs.
      A semantically incongruent word in the answer occurred either in focus or in non
      focus position as determined by the context, and this word was either accented or
      unaccented. Semantic incongruency elicited different N400 effects in different
      conditions. The largest N400 effect was found when the question-marked focus was
      accented, while the other three conditions elicited smaller N400 effects. The
      results suggest that context and accentuation interact. Thus accented focused
      words were processed more deeply compared to conditions where focus and
      accentuation mismatched, or when the new information had no marking. In addition,
      there seems to be sex differences in the depth of semantic processing. For males,
      a significant N400 effect was observed only when the question-marked focus was
      accented, reduced N400 effects were found in the other dialogues. In contrast,
      females produced similar N400 effects in all the conditions. These results
      suggest that regardless of external cues, females tend to engage in more
      elaborate semantic processing compared to males.

PMID- 21195103
TI  - Emotional modulation of the attentional blink: the neural structures involved in
      capturing and holding attention.
AB  - Perceiving a first target stimulus (T1) in a rapid serial visual presentation
      stream results in a transient impairment in detecting a second target (T2). This
      "attentional blink" is modulated by the emotional relevance of T1 and T2. The
      present experiment examined the neural underpinnings of the emotional modulation
      of the attentional blink. Behaviorally, the attentional blink was reduced for
      emotional T2 while emotional T1 led to a prolonged attentional blink. Using
      functional magnetic resonance imaging, we observed amygdala activation associated
      with the reduced attentional blink for emotional T2 in the face of neutral T1.
      The prolonged attentional blink following emotional T1 was correlated with
      enhanced activity in a cortical network including the anterior cingulate cortex,
      the insula and the orbitofrontal cortex. These results suggest that brain areas
      previously implicated in rather reflexive emotional reactions are responsible for
      the reduced attentional blink for emotional T2 whereas neural structures
      previously related to higher level processing of emotional information mediate
      the prolonged attentional blink following emotional T1.

PMID- 21195104
TI  - Spontaneous but not explicit processing of positive sentences impaired in
      Asperger's syndrome: pupillometric evidence.
AB  - Emotional prosody provides important cues for understanding the emotions of
      others in every day communication. Asperger's syndrome (AS) is a developmental
      disorder characterised by pronounced deficits in socio-emotional communication,
      including difficulties in the domain of prosody processing. We measured pupillary
      responses as an index of emotional prosodic processing when 15 participants with
      AS and 19 non-clinical control participants listened to positive, negative and
      neutral prosodic sentences. This occurred under a spontaneous and an explicit
      task instruction. In the explicit processing condition, the AS group and the non
      clinical controls showed increased pupil dilations to positively and negatively
      intoned sentences when judging the valence of that prosodic sentence. This
      suggests higher processing demands for emotionally arousing information, as the
      effect was not found in comparison to neutrally intoned sentences. In the
      spontaneous processing condition, controls also responded with increased pupil
      dilations to positively intoned sentences, whilst individuals with AS showed
      increased pupil dilations to negative sentences. The latter result is further
      supported by diminished ratings of emotionally intense sentences in the AS group
      compared to healthy controls. Perception and recognition of positively valenced
      sentences in individuals with AS appears impaired and dependent on the general
      task set-up. Diminished pupil dilations in spontaneous positive processing
      conditions as well as reduced positive valence ratings give strong indications
      for a general negative processing bias of verbal information for adult
      individuals diagnosed with AS.

PMID- 21195106
TI  - The fibrate drug gemfibrozil disrupts lipoprotein metabolism in rainbow trout.
AB  - Gemfibrozil (GEM) is a fibrate drug consistently found in effluents from sewage
      treatment plants. This study characterizes the pharmacological effects of GEM on
      the plasma lipoproteins of rainbow trout (Oncorhynchus mykiss). Our goals were to
      quantify the impact of the drug on: 1) lipid constituents of lipoproteins
      (phospholipids (PL), triacylglycerol (TAG), and cholesterol), 2) lipoprotein
      classes (high, low and very low density lipoproteins), and 3) fatty acid
      composition of lipoproteins. Potential mechanisms of GEM action were investigated
      by measuring lipoprotein lipase activity (LPL) and the hepatic gene expression of
      LPL and of the peroxisome proliferator-activated receptor (PPAR) alpha, beta, and
      gamma isoforms. GEM treatment resulted in decreased plasma lipoprotein levels (
      29%) and a reduced size of all lipoprotein classes (lower PL:TAG ratios).
      However, the increase in HDL-cholesterol elicited by GEM in humans failed to be
      observed in trout. Therefore, HDL-cholesterol cannot be used to assess the impact
      of the drug on fish. GEM also modified lipoprotein composition by reducing the
      abundance of long-chain n-3 fatty acids, thereby potentially reducing the
      nutritional quality of exposed fish. The relative gene expression of LPL was
      increased, but the activity of the enzyme was not, and we found no evidence for
      the activation of PPAR pathways. The depressing effects of GEM on fish
      lipoproteins demonstrated here may be a concern in view of the widespread
      presence of fibrates in aquatic environments. Work is needed to test whether
      exposure to environmental concentrations of these drugs jeopardizes the capacity
      of fish for reproduction, temperature acclimation or migratory behaviors.

PMID- 21195105
TI  - Explaining semantic short-term memory deficits: evidence for the critical role of
      semantic control.
AB  - Patients with apparently selective short-term memory (STM) deficits for semantic
      information have played an important role in developing multi-store theories of
      STM and challenge the idea that verbal STM is supported by maintaining activation
      in the language system. We propose that semantic STM deficits are not as
      selective as previously thought and can occur as a result of mild disruption to
      semantic control processes, i.e., mechanisms that bias semantic processing
      towards task-relevant aspects of knowledge and away from irrelevant information.
      We tested three semantic STM patients with tasks that tapped four aspects of
      semantic control: (i) resolving ambiguity between word meanings, (ii) sensitivity
      to cues, (iii) ignoring irrelevant information and (iv) detecting weak semantic
      associations. All were impaired in conditions requiring more semantic control,
      irrespective of the STM demands of the task, suggesting a mild, but task-general,
      deficit in regulating semantic knowledge. This mild deficit has a
      disproportionate effect on STM tasks because they have high intrinsic control
      demands: in STM tasks, control is required to keep information active when it is
      no longer available in the environment and to manage competition between items
      held in memory simultaneously. By re-interpreting the core deficit in semantic
      STM patients in this way, we are able to explain their apparently selective
      impairment without the need for a specialised STM store. Instead, we argue that
      semantic STM patients occupy the mildest end of spectrum of semantic control
      disorders.

PMID- 21195107
TI  - Studies on the dissociation of botulinum neurotoxin type A complexes.
AB  - The neurotoxins produced by the various strains of the anaerobic bacterium
      Clostridium botulinum naturally occur associated with complexing proteins which
      serve to protect the neurotoxins from the harsh environment of the mammalian
      gastrointestinal tract during bacterial invasion of the host. Three different
      complex species with the discrete sizes 19S (900 kDa, LL complex), 16S (500 kDa,
      L complex) and 12S (300 kDa, M complex) may be isolated from C. botulinum type A
      cultures. However, to affect their target cells these complexes must dissociate
      releasing the free 150 kDa neurotoxin. This study assesses the stability of these
      Clostridium botulinum neurotoxin serotype A (BoNT/A) complexes and identifies
      factors which influence their dissociation. The knowledge gained with purified
      toxin complexes was subsequently employed to analyze the presence of such
      complexes in the freeze or spray-dried commercial BoNT/A products Botox and
      Dysport in comparison to the complexing protein free product Xeomin. Purified 900
      kDa and 500 kDa toxin complex preparations show a pH and time dependent release
      of the 150 kDa neurotoxin with a half-life of less than a minute at pH values
      >7.0. At pH values of 6.25 or less, the complexes are stable. Furthermore,
      dilution of concentrated 900 kDa complexes leads to dissociation into 500 kDa,
      neurotoxin containing complexes. Addition of sodium chloride as contained in
      isotonic saline leads to further disruption of these complexes resulting in the
      release of the free 150 kDa neurotoxin. Examination of the commercial botulinum
      neurotoxin products Botox and Dysport using the same analytical procedures leads
      to the same conclusion: the dilution, drying and reconstitution processes of
      these products lead to a complete dissociation of 900 kDa complexes and 85% or
      more of neurotoxin are present in free form. CONCLUSION: BoNT A toxin complexes
      have evolved to quickly respond to specific environmental changes by efficient
      release of the neurotoxin. During pharmaceutical production and reconstitution of
      BoNT A products, the same principles effect the quantitative dissociation of 900
      kDa complexes and release of free neurotoxin prior to injection into target
      tissues.

PMID- 21195108
TI  - Chicken CCR6 and CCR7 are markers for immature and mature dendritic cells
      respectively.
AB  - In mammals, the CC chemokine receptors 6 and 7 (CCR6 and CCR7) play important
      roles in controlling the trafficking of dendritic cells (DC). CCR6 is expressed
      primarily on immature DC in the periphery and plays a role in the recruitment of
      immature DC to sites of potential antigen entry. On encountering pathogens, DC
      mature and migrate to secondary lymphoid organs where they present pathogen
      antigen to T cells to initiate specific adaptive immune responses. Maturation
      involves down-regulation of CCR6 but up-regulation of CCR7. To investigate the
      role of these two chemokine receptors in the function of DC in the chicken, a
      full-length chicken CCR7 (chCCR7) cDNA was cloned. Chicken CCR6 (chCCR6) was
      already available (Munoz et al., 2009). ChCCR7 shows the typical secondary
      structure of a seven-transmembrane G protein-coupled receptor and has 66% and 64%
      amino acid identity with human and mouse CCR7, respectively. Like its mammalian
      orthologues, chCCR7 mRNA was highly expressed in most lymphoid tissues (with the
      exception of the Harderian gland) and also in some non-lymphoid tissues
      (especially the heart, lung, skin and small intestine). Both chCCR6 and chCCR7
      were expressed at the mRNA level in immature chicken bone marrow-derived
      dendritic cells (chBM-DC), as measured by real-time quantitative RT-PCR. After DC
      maturation following stimulation with LPS or CD40L, expression levels of chCCR6
      mRNA were down-regulated, whereas those of chCCR7 were up-regulated, suggesting
      that these two chemokine receptors play a similar role in the trafficking of
      chicken DC as they do in mammals and that they act as markers of immature
      (chCCR6) and mature (chCCR7) DC.

PMID- 21195109
TI  - Fetal exposure to teratogens: evidence of genes involved in autism.
AB  - Environmental challenges during the prenatal period can result in behavioral
      abnormalities and cognitive deficits that appear later in life such as autism.
      Prenatal exposure to valproic acid, ethanol, thalidomide and misoprostol has been
      shown to be associated with an increased incidence of autism. In addition,
      rodents exposed in utero to some of these drugs show autism-like abnormalities,
      including brain changes and lifelong behavior dysfunction. Our aim is to
      summarize current understanding of the relationship between in utero exposure to
      these drugs and autism in humans and in autism-like animal model phenotypes. It
      also highlights the importance of these models to understanding the neurobiology
      of autism, particularly in the identification of susceptibility genes. These
      drugs are able to modulate the expression of many genes involved in processes
      such as proliferation, apoptosis, neuronal differentiation and migration,
      synaptogenesis and synaptic activity. It seems essential to focus research on
      genes expressed during early neurodevelopment which may be the target of
      mutations or affected by drugs such as those included in this review.

PMID- 21195110
TI  - Epidemiology, microbiology and outcomes of healthcare-associated and community
      acquired bacteremia: a multicenter cohort study.
AB  - OBJECTIVES: Classically, infections have been considered either nosocomial or
      community-acquired. Healthcare-associated infection represents a new
      classification intended to capture patients who have infection onset outside the
      hospital, but who, nonetheless, have interactions with the healthcare system.
      Regarding bloodstream infection (BSI), little data exist differentiating
      healthcare-associated bacteremia (HCAB) from community-acquired bacteremia (CAB).
      We studied the epidemiology and outcomes associated with HCAB. METHODS: We
      conducted a multicenter, retrospective chart review at 7 US hospitals, of
      consecutive patients admitted with a BSI during 2006, who met pre-defined
      selection criteria. We defined HCAB as a BSI in a patient who met >= 1 of the
      criteria: 1) hospitalization within 6 months; 2) immunosuppression; 3) chronic
      hemodialysis; or 4) nursing home residence. The rest were classified as CAB. We
      examined patient demographics, severity of illness, and in-hospital mortality
      rates by HCAB vs. CAB status. A bootstrap logistic regression model was developed
      to quantify the independent association between HCAB and hospital mortality.
      RESULTS: Of the total 1143 patients included, HCAB accounted for 63.7%, with the
      percentage ranging from 49.0% to 78.1% across centers. HCAB patients were older
      (58.5 +/- 17.5 vs. 55.0 +/- 19.9 years, p = 0.003) and slightly more likely to be
      male (56.1% vs. 50.2%, p = 0.044) than those with CAB. HCAB was associated with a
      higher mean Acute Physiology Score (12.6 +/- 6.2 vs. 11.4 +/- 5.7, p = 0.009) and
      recent hospitalization was the most prevalent criteria for defining HCAB (76.5%).
      Hospital LOS was longer in the HCAB (median 8, IQR 5-15 days) than CAB (median 7,
      IQR 4-13 days) group (p = 0.030). In a multivariable model, the risk of hospital
      death was 3-fold higher for HCAB compared to CAB (adjusted odds ratio 3.13, 95%
      CI 1.75-5.50, p < 0.001, AUROC = 0.812). CONCLUSIONS: HCAB accounts for a
      substantial proportion of all patients with BSIs admitted to the hospital. HCAB
      is associated with a higher mortality rate than CAB. Physicians should recognize
      that HCAB is responsible for many BSIs presenting to the hospital and may
      represent a distinct clinical group from CAB.

PMID- 21195111
TI  - Early detection of influenza A(H5) viruses with affinity for the human sialic
      acid receptor by MALDI-TOF mass spectrometry based mutation detection.
AB  - Highly pathogenic avian influenza (HPAI) A(H5N1) strains have been causing
      sporadic cases of disease in South East Asia and Africa for many years. These
      cases are associated with a high fatality rate, and it is feared that the virus
      could evolve into a strain capable of causing a pandemic. It is likely that a
      requirement for a A(H5) pandemic to occur is a switch in the receptor affinity of
      the virus. Candidate mutations in the hemagglutinin glycoprotein have been
      identified in the literature, and their emergence in circulating viruses would be
      an ominous development. This study describes a method to identify the presence of
      these mutations, even within a quasispecies, using RT-PCR followed by in vitro
      translation and peptide characterization by MALDI-TOF mass spectrometry.

PMID- 21195112
TI  - Futile import of tRNAs and proteins into the mitochondrion of Trypanosoma brucei
      evansi.
AB  - Trypanosoma brucei brucei has two distinct developmental stages, the procyclic
      stage in the insect and the bloodstream stage in the mammalian host. The
      significance of each developmental stage is punctuated by specific changes in
      metabolism. In the insect, T. b. brucei is strictly dependent on mitochondrial
      function and thus respiration to generate the bulk of its ATP, whereas in the
      mammalian host it relies heavily on glycolysis. These observations have raised
      questions about the importance of mitochondrial function in the bloodstream
      stage. Peculiarly, akinetoplastic strains of Trypanosoma brucei evansi that lack
      mitochondrial DNA do exist in the wild and are developmentally locked in the
      glycolysis-dependent bloodstream stage. Using RNAi we show that two mitochondrion
      imported proteins, mitochondrial RNA polymerase and guide RNA associated protein
      1, are still imported into the nucleic acids-lacking organelle of T. b. evansi,
      making the need for these proteins futile. We also show that, like in the T. b.
      brucei procyclic stage, the mitochondria of both bloodstream stage of T. b.
      brucei and T. b. evansi import various tRNAs, including those that undergo
      thiolation. However, we were unable to detect mitochondrial thiolation in the
      akinetoplastic organelle. Taken together, these data suggest a lack of connection
      between nuclear and mitochondrial communication in strains of T. b. evansi that
      lost mitochondrial genome and that do not required an insect vector for survival.

PMID- 21195113
TI  - Fluorescence in situ hybridization (FISH) mapping of single copy genes on
      Trichomonas vaginalis chromosomes.
AB  - The highly repetitive nature of the Trichomonas vaginalis genome and massive
      expansion of various gene families has caused difficulties in genome assembly and
      has hampered genome mapping. Here, we adapted fluorescence in situ hybridization
      (FISH) for T. vaginalis, which is sensitive enough to detect single copy genes on
      metaphase chromosomes. Sensitivity of conventional FISH, which did not allow
      single copy gene detection in T. vaginalis, was increased by means of tyramide
      signal amplification. Two selected single copy genes, coding for serine
      palmitoyltransferase and tryptophanase, were mapped to chromosome I and II,
      respectively, and thus could be used as chromosome markers. This established
      protocol provides an amenable tool for the physical mapping of the T. vaginalis
      genome and other essential applications, such as development of genetic markers
      for T. vaginalis genotyping.

PMID- 21195114
TI  - TgVTC2 is involved in polyphosphate accumulation in Toxoplasma gondii.
AB  - Polyphosphate is found in every cell, having roles in diverse processes,
      including differentiation and response to stress. In this study, we characterize
      a Toxoplasma gondii mutant containing an insertion within the carboxy-terminal
      end of a homolog of Saccharomyces cerevisiae Vtc2p, a component of the
      polyphosphate synthetic machinery. Locus TgVTC2 encodes a 140kDa protein
      containing conserved SPX, VTC and transmembrane domains. TgVTC2 localizes in
      punctate spots within the cytoplasm that do not co-localize with known markers.
      The TgVTC2 mutant showed dramatically reduced polyphosphate accumulation, a
      defect restored by introduction of TgVTC2 to the mutant. Insertion within TgVTC2
      resulted in increased transcript levels for two loci, including a putative FIKK
      kinase. These transcript levels were restored to wild-type levels upon
      complementation with the TgVTC2 locus. The TgVTC2 locus was refractory to
      knockout, and may be essential. Analysis of this TgVTC2 mutant will facilitate
      dissection of the T. gondii polyphosphate synthesis pathway.

PMID- 21195115
TI  - Structure determination of glycogen synthase kinase-3 from Leishmania major and
      comparative inhibitor structure-activity relationships with Trypanosoma brucei
      GSK-3.
AB  - Glycogen synthase kinase-3 (GSK-3) is a drug target under intense investigation
      in pharmaceutical companies and constitutes an attractive piggyback target for
      eukaryotic pathogens. Two different GSKs are found in trypanosomatids, one about
      150 residues shorter than the other. GSK-3 short (GeneDB: Tb927.10.13780) has
      previously been validated genetically as a drug target in Trypanosoma brucei by
      RNAi induced growth retardation; and chemically by correlation between enzyme and
      in vitro growth inhibition. Here, we report investigation of the equivalent GSK-3
      short enzymes of L. major (LmjF18.0270) and L. infantum (LinJ18_V3.0270,
      identical in amino acid sequences to LdonGSK-3 short) and a crystal structure of
      LmajGSK-3 short at 2 A resolution. The inhibitor structure-activity relationships
      (SARs) of L. major and L. infantum are virtually identical, suggesting that
      inhibitors could be useful for both cutaneous and visceral leishmaniasis.
      Leishmania spp. GSK-3 short has different inhibitor SARs than TbruGSK-3 short,
      which can be explained mostly by two variant residues in the ATP-binding pocket.
      Indeed, mutating these residues in the ATP-binding site of LmajGSK-3 short to the
      TbruGSK-3 short equivalents results in a mutant LmajGSK-3 short enzyme with SAR
      more similar to that of TbruGSK-3 short. The differences between human GSK-3beta
      (HsGSK-3beta) and LmajGSK-3 short SAR suggest that compounds which selectively
      inhibit LmajGSK-3 short may be found.

PMID- 21195116
TI  - Molecular biology of Bax and Bak activation and action.
AB  - Bax and Bak are two nuclear-encoded proteins present in higher eukaryotes that
      are able to pierce the mitochondrial outer membrane to mediate cell death by
      apoptosis. Thus, organelles recruited by nucleated cells to supply energy can be
      recruited by Bax and Bak to kill cells. The two proteins lie in wait in healthy
      cells where they adopt a globular alpha-helical structure, seemingly as monomers.
      Following a variety of stress signals, they convert into pore-forming proteins by
      changing conformation and assembling into oligomeric complexes in the
      mitochondrial outer membrane. Proteins from the mitochondrial intermembrane space
      then empty into the cytosol to activate proteases that dismantle the cell. The
      arrangement of Bax and Bak in membrane-bound complexes, and how the complexes
      porate the membrane, is far from being understood. However, recent data indicate
      that they first form symmetric BH3:groove dimers which can be linked via an
      interface between the alpha6-helices to form high order oligomers. Here, we
      review how Bax and Bak change conformation and oligomerize, as well as how
      oligomers might form a pore. This article is part of a Special Issue entitled
      Mitochondria: the deadly organelle.

PMID- 21195117
TI  - Presenilin-1 processing of ErbB4 in fetal type II cells is necessary for control
      of fetal lung maturation.
AB  - Maturation of pulmonary fetal type II cells to initiate adequate surfactant
      production is crucial for postnatal respiratory function. Little is known about
      specific mechanisms of signal transduction controlling type II cell maturation.
      The ErbB4 receptor and its ligand neuregulin (NRG) are critical for lung
      development. ErbB4 is cleaved at the cell membrane by the gamma-secretase enzyme
      complex whose active component is either presenilin-1 (PSEN-1) or presenilin-2.
      ErbB4 cleavage releases the 80kDa intracellular domain (4ICD), which associates
      with chaperone proteins such as YAP (Yes-associated protein) and translocates to
      the nucleus to regulate gene expression. We hypothesized that PSEN-1 and YAP have
      a development-specific expression in fetal type II cells and are important for
      ErbB4 signaling in surfactant production. In primary fetal mouse E16, E17, and
      E18 type II cells, PSEN-1 and YAP expression increased at E17 and E18 over E16.
      Subcellular fractionation showed a strong cytosolic and a weaker membrane
      location of both PSEN-1 and YAP. This was enhanced by NRG stimulation. Co
      immunoprecipitations showed ErbB4 associated separately with PSEN-1 and with YAP.
      Their association, phosphorylation, and co-localization were induced by NRG.
      Confocal immunofluorescence and nuclear fractionation confirmed these
      associations in a time-dependent manner after NRG stimulation. Primary ErbB4
      deleted E17 type II cells were transfected with a mutant ErbB4 lacking the gamma
      secretase binding site. When compared to transfection with wild-type ErbB4, the
      stimulatory effect of NRG on surfactant protein mRNA expression was lost. We
      conclude that PSEN-1 and YAP have crucial roles in ErbB4 signal transduction
      during type II cell maturation.

PMID- 21195118
TI  - Phosphorylation of dynamin II at serine-764 is associated with cytokinesis.
AB  - Calcineurin is a phosphatase that is activated at the last known stage of
      mitosis, abscission. Among its many substrates, it dephosphorylates dynamin II
      during cytokinesis at the midbody of dividing cells. However, dynamin II has
      several cellular roles including clathrin-mediated endocytosis, centrosome
      cohesion and cytokinesis. It is not known whether dynamin II phosphorylation
      plays a role in any of these functions nor have the phosphosites involved in
      cytokinesis been directly identified. We now report that dynamin II from rat lung
      is phosphorylated to a low stoichiometry on a single major site, Ser-764, in the
      proline-rich domain. Phosphorylation on Ser-764 also occurred in asynchronously
      growing HeLa cells and was greatly increased upon mitotic entry. Tryptic phospho
      peptides isolated by TiO(2) chromatography revealed only a single phosphosite in
      mitotic cells. Mitotic phosphorylation was abolished by roscovitine, suggesting
      the mitotic kinase is cyclin-dependent kinase 1. Cyclin-dependent kinase 1
      phosphorylated full length dynamin II and Glutathione-S-Transferase-tagged
      dynamin II-proline-rich domain in vitro, and mutation of Ser-764 to alanine
      reduced proline-rich domain phosphorylation by 80%, supporting that there is only
      a single major phosphosite. Ser-764 phosphorylation did not affect clathrin
      mediated endocytosis or bulk endocytosis using penetratin-based phospho-deficient
      or phospho-mimetic peptides or following siRNA depletion/rescue experiments.
      Phospho-dynamin II was enriched at the mitotic centrosome, but this targeting was
      unaffected by the phospho-deficient or phospho-mimetic peptides. In contrast, the
      phospho-mimetic peptide displaced endogenous dynamin II, but not calcineurin,
      from the midbody and induced cytokinesis failure. Therefore, phosphorylation of
      dynamin II primarily occurs on a single site that regulates cytokinesis
      downstream of calcineurin, rather than regulating endocytosis or centrosome
      function.

PMID- 21195119
TI  - Intergenotypic chimeric hepatitis E viruses (HEVs) with the genotype 4 human HEV
      capsid gene in the backbone of genotype 3 swine HEV are infectious in pigs.
AB  - Genotypes 1 and 2 hepatitis E virus (HEV) infect only humans whereas genotypes 3
      and 4 HEV infect both humans and pigs. To evaluate the mechanism of cross-species
      HEV infection between humans and swine, in this study we constructed five
      intergenotypic chimeric viruses and tested for their infectivity in vitro and in
      pigs. We demonstrated that chimeric viruses containing the ORF2 capsid gene
      either alone or in combination with its adjacent 5' junction region (JR) and 3'
      noncoding region (NCR) from a genotype 4 human HEV in the backbone of a genotype
      3 swine HEV are replication-competent in Huh7 cells and infectious in HepG2/C3A
      cells and in pigs, and thus supporting the hypothesis that genotypes 3 and 4
      human HEV are of swine origin. However, chimeric viruses containing the
      JR+ORF2+3' NCR of genotypes 3 or 4 HEV in the backbone of genotype 1 human HEV
      failed to infect pigs, suggesting that other genomic regions such as 5' NCR and
      ORF1 may also be involved in HEV cross-species infection. The results from this
      study provide the first experimental evidence of the exchangeability of the
      capsid gene between genotype 3 swine HEV and genotype 4 human HEV, and have
      important implications for understanding the mechanism of HEV cross-species
      infection.

PMID- 21195120
TI  - A synergistic effect of GABA tea and copper(II) on DNA breakage in human
      peripheral lymphocytes.
AB  - GABA tea is a tea product that contains a high level of gamma-aminobutyric acid
      (GABA). The oxidant and antioxidant roles of GABA tea in DNA damage were
      investigated in this study. DNA cleavage was observed by GABA-tea extract in the
      presence of copper ions. Comet assay revealed that combination of GABA-tea
      extract, but not pure GABA, and Cu(2+) is capable of oxidatively degrading
      cellular DNA in human peripheral lymphocytes. Using various reactive oxygen
      scavengers, we found that catalase and sodium azide effectively inhibited GABA
      tea extract/Cu(II)-induced DNA degradation, suggesting the essential role of
      singlet oxygen and H(2)O(2) in the reaction. In addition, neocuproine inhibited
      the DNA degradation, confirming that Cu(I) is an intermediate in the DNA cleavage
      reaction. Therefore, we speculate that GABA-tea extract/Cu(II)-induced DNA damage
      is probably mediated through the formation of H(2)O(2) and the reduction of
      copper. Furthermore, our data showed that GABA-tea extract was more genotoxic and
      pro-oxidant than its major catechin constituent, (-)-epigallocatechin-3-gallate
      (EGCG), leading to DNA cleavage in the presence of Cu(2+). These findings will
      provide implications for the potential of GABA-tea extract in anticancer
      property, which may involve copper ions and the consequent pro-oxidant action.

PMID- 21195121
TI  - The role of nitric oxide in convulsions induced by lindane in rats.
AB  - Lindane is an organochloride pesticide and scabicide. It evokes convulsions
      mainly trough the blockage of GABA(A) receptors. Nitric oxide (NO), gaseous
      neurotransmitter, has contradictor role in epileptogenesis due to opposite
      effects of L-arginine, precursor of NO syntheses (NOS), and L-NAME (NOS
      inhibitor) observed in different epilepsy models. The aim of the current study
      was to determine the effects of NO on the behavioral and EEG characteristics of
      lindane-induced epilepsy in male Wistar albino rats. The administration of L
      arginine (600, 800 and 1000 mg/kg, i.p.) in dose-dependent manner significantly
      increased convulsion incidence and severity and shortened latency time to first
      convulsion elicited by lower lindane dose (4 mg/kg, i.p.). On the contrary,
      pretreatment with L-NAME (500, 700 and 900 mg/kg, i.p.) decreased convulsion
      incidence and severity and prolonged latency time to convulsion following
      injection with a convulsive dose of lindane (8 mg/kg, i.p.). EEG analyses showed
      increase of number and duration of ictal periods in EEG of rats receiving l
      arginine prior to lindane and decrease of this number in rats pretreated with L
      NAME. These results support the conclusion that NO plays a role of endogenous
      convulsant in rat model of lindane seizures.

PMID- 21195122
TI  - Efficacy of natural antimicrobials in toothpaste formulations against oral
      biofilms in vitro.
AB  - OBJECTIVES: To evaluate the antimicrobial efficacies of two toothpaste
      formulations containing natural antimicrobials (herbal extracts and chitosan)
      against oral biofilms of different composition and maturational status. METHODS:
      Bacteria from a buffer suspension or fresh saliva were adhered for 2h to a
      salivary conditioning film and subsequently grown for 16h. Dual-species biofilms
      were prepared from Actinomyces naeslundii T14V-J1 and Streptococcus oralis J22,
      whilst multi-species biofilms were grown from freshly collected human saliva.
      Biofilms were exposed to 25wt% toothpaste supernatants. A chlorhexidine
      containing mouthrinse and a buffer were used as positive- and negative-controls,
      respectively. Antibacterial efficacy was concluded from acute killing, bacterial
      removal, prevention of bacterial re-deposition and continued killing during re
      deposition. RESULTS: The herbal- and chitosan-based supernatants showed immediate
      killing of oral biofilm bacteria, comparable with chlorhexidine. Moreover,
      exposure of a biofilm to these supernatants or chlorhexidine, yielded ongoing
      killing of biofilm bacteria after exposure during re-deposition of bacteria to a
      matured 16h biofilm, but not to a much thinner initial biofilm formed by 2h
      adhesion only. This suggests that thicker, more matured biofilms can absorb and
      release oral antimicrobials. CONCLUSIONS: Supernatants based on herbal- and
      chitosan-based toothpastes have comparable immediate and ongoing antibacterial
      efficacies as chlorhexidine. Natural antimicrobials and chlorhexidine absorb in
      oral biofilms which contributes to their substantive action.

PMID- 21195123
TI  - Age of failed restorations: A deceptive longevity parameter.
AB  - There is pressing need to enhance evidence base in respect of longevity of
      restorations. Currently, there is lack of appreciation of differences between
      survival data based on the age of failed restorations as compared to gold
      standard Kaplan-Meier statistics. OBJECTIVES: This study was undertaken to
      compare and contrast longevity data for a number of data sets. It investigated if
      restoration longevity, as calculated by the Kaplan-Meier method, is different
      from longevity according to the median survival time of failed restorations.
      METHODS: Existing clinical datasets of dental restorations and an artificial
      dataset were used to calculate longevity according to Kaplan-Meier statistics and
      by means of calculation of median age of failed restorations. RESULTS: The
      findings indicate that median age of failed restorations may be considered as a
      deceptive measure of restoration longevity. Specially extending the duration of
      longitudinal studies of restorations apparently leads to higher values for median
      age of failed restorations. Restorations of materials that tend to exhibit early
      failures may have lower values for median age of failed restorations, compared to
      restorations of different materials which tend to exhibit failures later in
      clinical service, and thereby not giving a true measure of overall restoration
      longevity. CONCLUSION: In absence of all dates of placement and failure for a
      series of restorations a reliable measure of restoration longevity is not yet
      available. Kaplan-Meier statistics remains the preferred method of calculating
      longevity of a group of dental restorations.

PMID- 21195124
TI  - Azithromycin inhibits macrophage interleukin-1beta production through inhibition
      of activator protein-1 in lipopolysaccharide-induced murine pulmonary
      neutrophilia.
AB  - Macrolide antibiotics, including azithromycin, also possess anti-inflammatory
      properties. However, the molecular mechanism(s) of activity as well as the target
      cells for their action have not been unambiguously identified as yet. In this
      study, the effects of azithromycin on lipopolysaccharide (LPS)-induced pulmonary
      neutrophilia were investigated in mice. Using immunohistochemistry, mRNA and
      specific protein assays, we confirmed that azithromycin ameliorates LPS-induced
      pulmonary neutrophilia by inhibiting interleukin-1beta (IL-1beta) expression and
      production selectively in alveolar macrophages as well as in LPS-stimulated
      J774.2 macrophage-derived cells in vitro. Inhibition by azithromycin of
      neutrophilia and IL-1beta was accompanied by prevention of nuclear expression of
      activator protein-1 (AP-1) in both alveolar macrophages and J774.2 cells. The
      macrolide did not alter nuclear factor kappa B (NF-kappaB) or extracellular
      signal-regulated kinase 1/2 (ERK1/2) expression, activation or localization in
      LPS-stimulated lungs or in J774.2 cells. In conclusion, we have shown that
      inhibition of LPS-induced pulmonary neutrophilia and IL-1beta concentrations in
      lung tissue following azithromycin treatment is mediated through effects on
      alveolar macrophages. In addition, we have shown for the first time, in an in
      vivo model, that azithromycin inhibits AP-1 activation in alveolar macrophages,
      an action confirmed on J774.2 cells in vitro.

PMID- 21195125
TI  - Dimethyl sulfoxide enhances GLUT4 translocation through a reduction in GLUT4
      endocytosis in insulin-stimulated 3T3-L1 adipocytes.
AB  - Insulin increases muscle and fat cell glucose uptake by inducing the
      translocation of glucose transporter GLUT4 from intracellular compartments to the
      plasma membrane. Here, we have demonstrated that in 3T3-L1 adipocytes, DMSO at
      concentrations higher than 7.5% augmented cell surface GLUT4 levels in the
      absence and presence of insulin, but that at lower concentrations, DMSO only
      enhanced GLUT4 levels in insulin-stimulated cells. At a 5% concentration, DMSO
      also increased cell surface levels of the transferrin receptor and GLUT1. Glucose
      uptake experiments indicated that while DMSO enhanced cell surface glucose
      transporter levels, it also inhibited glucose transporter activity. Our studies
      further demonstrated that DMSO did not sensitize the adipocytes for insulin and
      that its effect on GLUT4 was readily reversible (t1/2~12 min) and maintained in
      insulin-resistant adipocytes. An enhancement of insulin-induced GLUT4
      translocation was not observed in 3T3-L1 preadipocytes and L6 myotubes,
      indicating cell specificity. DMSO did not enhance insulin signaling nor
      exocytosis of GLUT4 vesicles, but inhibited GLUT4 internalization. While other
      chemical chaperones (glycerol and 4-phenyl butyric acid) also acutely enhanced
      insulin-induced GLUT4 translocation, these effects were not mediated via changes
      in GLUT4 endocytosis. We conclude that DMSO is the first molecule to be described
      that instantaneously enhances insulin-induced increases in cell surface GLUT4
      levels in adipocytes, at least in part through a reduction in GLUT4 endocytosis.

PMID- 21195126
TI  - A model of stepping kinetics for rotary enzymes. Application to the F1-ATPase.
AB  - Our simple kinetic model, based on the classic "binding change mechanism",
      describes the stepping kinetics for the rotary enzyme motors. The model shows
      that the cooperative interactions between active sites in the motor enzyme F1
      ATPase induce the stepping product release. This phenomenon results from non
      harmonic oscillations in the enzyme forms. The found rate constants,
      corresponding to the stepping phenomenon, are close to the rate constants known
      for the F1-ATPase. The duration of dwells during the product release is shown to
      depend on the ATP concentration in accordance with the known experimental data.

PMID- 21195127
TI  - Curcumin diminishes the impacts of hyperglycemia on the activation of hepatic
      stellate cells by suppressing membrane translocation and gene expression of
      glucose transporter-2.
AB  - Diabetes is featured by elevated levels of blood glucose, i.e. hyperglycemia,
      which might be a risk factor for hepatic fibrogenesis in patients with non
      alcoholic steatohepatitis. Hepatic stellate cells (HSCs) are the major effectors
      during hepatic fibrogenesis. This study was designed to evaluate impacts of high
      levels of glucose on HSC activation, assess roles of the phytochemical curcumin
      in attenuating the glucose impacts, and elucidate underlying mechanisms. In this
      report, levels of intracellular glucose were measured. Contents and gene
      expression of glucose transporter-2 (GLUT2) in cell fractions were examined.
      Levels of cellular glutathione and oxidative stress were analyzed. We observed
      that high levels of glucose induced cell proliferation, type I collagen
      production and expression of genes relevant to HSC activation, and elevated
      intracellular glucose levels in cultured HSCs. Curcumin eliminated the
      stimulatory impacts. Curcumin abrogated the membrane translocation of GLUT2 by
      interrupting the p38 MAPK signaling pathway. In addition, curcumin suppressed
      glut2 expression by stimulating the activity of peroxisome proliferator-activated
      receptor-gamma (PPARgamma) and de novo synthesis of glutathione. In conclusion,
      hyperglycemia stimulated HSC activation in vitro by increasing intracellular
      glucose, which was eliminated by curcumin by blocking the membrane translocation
      of GLUT2 and suppressing glut2 expression. The latter was mediated by activating
      PPARgamma and attenuating oxidative stress. Our results presented evidence to
      impacts of hyperglycemia on stimulating HSC activation and hepatic fibrogenesis,
      and provided novel insights into the mechanisms by which curcumin eliminated the
      hyperglycemia-caused HSC activation and potential therapeutic strategies for
      treatment of diabetes-associated hepatic fibrogenesis.

PMID- 21195128
TI  - Adrenocorticotropin hormone (ACTH) effects on MAPK phosphorylation in human
      fasciculata cells and in embryonic kidney 293 cells expressing human melanocortin
      2 receptor (MC2R) and MC2R accessory protein (MRAP)beta.
AB  - Adrenocorticotropin hormone (ACTH) exerts trophic effects on adrenocortical
      cells. We studied the phosphorylation of mitogen-activated proteins kinases
      (MAPKs) in human embryonic kidney cells stably expressing the ACTH receptor,
      MC2R, and its accessory protein MRAPbeta and in primary cultures of human adrenal
      fasciculata cells. ACTH induced a maximal increase in p44/p42(mapk) and of p38
      MAPK phosphorylation after 5min. Neither the overexpression of wild-type
      arrestin2, arrestin3 or their respective dominant negative forms affected
      p44/p42(mapk) phosphorylation. However, preincubation with the recycling
      inhibitors brefeldin A and monensin attenuated both cAMP accumulation and
      p44/p42(mapk) phosphorylation proportionally. Cyclic AMP-related PKA inhibitors
      (H89, KI(6-22)) and Rp-cAMPS decreased p44/p42(mapk) phosphorylation but not ACTH
      mediated cAMP production. The selective Epac1/2 activator, 8-pCPT-2'-O-MecAMP,
      did not modify the effect of ACTH. Thus, cAMP/PKA, but not cAMP/Epac1/2 pathways,
      or arrestin-coupled internalization of MC2R is involved in ACTH-induced
      p44/p42(mapk) phosphorylation by human MC2R. Together, ACTH binding to MC2R
      stimulates PKA-dependent p44/p42(mapk) phosphorylation.

PMID- 21195129
TI  - Regulation of steroid production: analysis of Cyp11a1 promoter.
AB  - CYP11A1 is a key enzyme in steroid synthesis abundantly expressed in the adrenal,
      testis, ovary, and placenta. This article reviews recent studies on cis
      regulatory elements and trans-regulators of the CYP11A1 promoter, with special
      focus on their tissue-specific regulation. Trans-regulators include tissue
      specific factors such as SF-1, DAX-1, TReP-132, LBP, and GATA that regulate
      tissue-specific expression of CYP11A1. These tissue-specific factors interact
      with factors commonly present in most cells like AP-1, Sp1, and AP-2 to bring
      CYP11A1 transcription to full potential. These transcription factors stimulate
      CYP11A1 transcriptional activity through interaction with their specific cis
      elements or through protein-protein interaction. The cis-element on the Cyp11a1
      promoter was further characterized in vitro and in vivo. Mutation of the proximal
      SF-1-binding site results in down regulation of CYP11A1 in the adrenal and testis
      but not in the ovary and placenta, leading to attenuated corticosterone circadian
      rhythms and blunted stress response.

PMID- 21195130
TI  - Genetic modifications of mouse proopiomelanocortin peptide processing.
AB  - Pro-opiomelanocortin (POMC) is a prohormone which undergoes extensive tissue and
      cell specific post-translational processing producing a number of active peptides
      with diverse biological roles ranging from control of adrenal function to
      pigmentation to the regulation of feeding. One approach to unraveling the
      complexities of the POMC system is to engineer mouse mutants which lack specific
      POMC peptides. We describe here the design, generation, validation, and
      preliminary analysis of one such partial POMC mutant specifically lacking alpha
      MSH. In contrast to POMC null mutant mice, mice lacking alpha-MSH in the presence
      of all other POMC peptides maintain adrenal structures and produce corticosterone
      comparable to wildtype littermates; however, they still have decreased levels of
      aldosterone, as found in POMC null mutant mice. Our findings demonstrate that
      alpha-MSH is not needed for maintenance of adrenal structure or for
      corticosterone production, but is needed for aldosterone production. These data
      demonstrate that mouse strains generated with precise genetic modifications of
      POMC peptide processing can answer questions about POMC peptide function. Further
      analysis of this and additional strains of mice with modified POMC peptide
      processing patterns will open up a novel avenue for studying the roles of
      individual POMC peptides.

PMID- 21195131
TI  - Direct effect of dehydroepiandrosterone sulfate (DHEAS) on PC-12 cell
      differentiation processes.
AB  - Dehydroepiandrosterone sulfate is classically seen as an inactive reservoir for
      the production of dehydroepiandrosterone. Steroid sulfatase is the enzyme that
      catalyzes the hydrolysis of dehydroepiandrosterone sulfate to
      dehydroepiandrosterone, which can then be further metabolized to other steroid
      hormones. Recent studies, however, indicate that dehydroepiandrosterone sulfate
      can mediate biological effects without being converted to dehydroepiandrosterone.
      This study aims to evaluate whether dehydroepiandrosterone sulfate itself
      influences the differentiation of PC-12 cells or if its desulfation to
      dehydroepiandrosterone is required. dehydroepiandrosterone and
      dehydroepiandrosterone sulfate both influence the differentiation of chromaffin
      PC-12 cells. Blocking steroid sulfatase activity and thereby the conversion of
      dehydroepiandrosterone sulfate to dehydroepiandrosterone by the enzyme blocker
      estrone sulfamate showed that the effect of dehydroepiandrosterone sulfate is
      independent of its conversion to dehydroepiandrosterone. Dehydroepiandrosterone
      sulfate, similar to dehydroepiandrosterone, reduced nerve growth factor-induced
      neurite outgrowth of PC-12 cells and the expression of synaptosomal-associated
      membrane protein of 25 kDa, increased the expression of chromogranin A and
      significantly increased dopamine release of PC-12 cells. In addition,
      dehydroepiandrosterone sulfate, dehydroepiandrosterone and membrane impermeable
      dehydroepiandrosterone-BSA all significantly reduced NGF-induced MAPK ERK1/2
      signaling after 5 min. In summary, this study provides evidence that
      dehydroepiandrosterone sulfate, independent of its conversion to
      dehydroepiandrosterone, directs PC-12 cells' differentiation to a neuroendocrine
      direction. Furthermore, employing membrane-impermeable dehydroepiandrosterone-BSA
      indicates the involvement of plasma-membrane bound receptors.

PMID- 21195132
TI  - Identification of neonatal rat hippocampal radial glia cells in vitro.
AB  - The role of radial glia cells (RGCs) as neural progenitors and as guides for
      migrating neurons is well established, whereas their precise contribution to
      adult hippocampal neurogenesis remains less understood. To precisely study the
      properties of hippocampal RGCs under normal conditions in vitro, here we acquired
      the hippocampal RGCs of postnatal 1 d rats under adherent conditions in vitro,
      identified their astroglia and stem/progenitor properties. We found that the
      neonatal rat hippocampal RGCs had longer processes than the RGCs from fetal
      cerebral cortices, and these cells could be double-labeled by BLBP, GFAP,
      Vimentin with Nestin and expressed some stem/progenitor genes, these cells also
      presented multiple differentiation potentialities, albeit the ability of
      gliogenesis far exceeded the neurogenesis under normal culture conditions in
      vitro. Taken together, we acquired and identified some properties of the RGCs
      from neonatal rat hippocampi in vitro.

PMID- 21195133
TI  - Role of different types of potassium channels and peroxisome proliferator
      activated receptors gamma in the antidepressant-like activity of bis selenide in
      the mouse tail suspension test.
AB  - In the present study we investigated the role of potassium (K(+)) channels and
      peroxisome proliferator-activated receptor gamma (PPARgamma) in the
      antidepressant-like effect of bis selenide in the mouse tail suspension test
      (TST). Intracerebroventricular (i.c.v.) pretreatment with tetraethyl ammonium
      (TEA, a non-specific inhibitor of K(+) channels, 25 pg/site), glibenclamide (an
      ATP-sensitive K(+) channel inhibitor, 0.5 pg/site), charybdotoxin (a large and
      intermediate conductance calcium-activated K(+) channel inhibitor, 25 pg/site) or
      apamin (a small-conductance calcium-activated K(+) channel inhibitor, 10 pg/site)
      produced a synergistic action with a sub effective dose of bis selenide (0.1
      mg/kg, per oral--p.o.). Picrotoxin (1 mg/kg, intraperitoneally--i.p.)
      pretreatment did not prevent the reduction in immobility time elicited by bis
      selenide (1 mg/kg, p.o.) in the TST. The reduction in the immobility time
      elicited by an effective dose of bis selenide (1 mg/kg, p.o.) was prevented by
      the pretreatment of mice with cromakalim, minoxidil (K(+) channel openers, 10
      MUg/site, i.c.v.) and GW 9662 (a PPARgamma antagonist, 10 MUg/site, i.c.v.). The
      findings clearly suggest that an acute oral dose of bis selenide produced an
      antidepressant-like effect in the mouse TST by a mechanism that involves the K(+)
      channels and PPARgamma receptors.

PMID- 21195134
TI  - Vulnerability to nicotine abstinence-related social anxiety-like behavior:
      molecular correlates in neuropeptide Y, Y2 receptor and corticotropin releasing
      factor.
AB  - An outbred rat model of the novelty-seeking phenotype is used to study nicotine
      vulnerability, where experimentally naive rats were phenotype screened as high or
      low responders (HRs or LRs, ranking in the upper or lower one-third of the
      population respectively) based on locomotor activity displayed in a novel
      environment. Following nicotine training and abstinence, HR animals pre-trained
      with nicotine showed expression of locomotor sensitization to nicotine challenge
      along with enhanced social anxiety-like behavior in the social interaction test
      compared to saline pre-trained controls. HR rats also showed a downregulation in
      neuropeptide Y (NPY) mRNA levels in the medial nucleus of amygdala and the CA1
      field of the hippocampus, an upregulation in Y2 mRNA levels in the CA3 field of
      the hippocampus, and an upregulation in the corticotropin releasing factor (CRF)
      mRNA levels in the central nucleus of the amygdala. These findings implicate
      dysregulations in the NPY-CRF systems in the HR hippocampus and amygdala
      associated with the emergence of social anxiety-like behavior, and a novel Y2R
      mediated pathway in nicotine relapse.

PMID- 21195135
TI  - Localization of Broca's area using verb generation tasks in the MEG: validation
      against fMRI.
AB  - Functional MRI (fMRI) is routinely used to non-invasively localize language
      areas. Magnetoencephalography (MEG) is being explored as an alternative
      technique. MEG tasks to localize receptive language are well established although
      there are no standardized tasks to localize expressive language areas. We
      developed two expressive language tasks for MEG and validated their localizations
      against fMRI data. Ten right-handed adolescents (MU=17.5 years) were tested with
      fMRI and MEG on two tasks: verb generation to pictures and verb generation to
      words. MEG and fMRI data were normalized and overlaid. The number of overlapping
      voxels activated in fMRI and MEG were counted for each subject, for each task, at
      different thresholding levels. For picture verb generation, there was 100%
      concordance between MEG and fMRI lateralization, and for word verb generation,
      there was 75% concordance. A count showed 79.6% overlap of voxels activated by
      both MEG and fMRI for picture verb generation and 50.2% overlap for word verb
      generation. The percentage overlap decreased with increasingly stringent
      activation thresholds. Our novel MEG expressive language tasks successfully
      identified neural regions involved in language production and showed high
      concordance with fMRI laterality. Percentage overlap of activated voxels was also
      high when validated against fMRI, but showed task-specific and threshold-related
      effects. The high concordance and high percentage overlap between fMRI and MEG
      activations confirm the validity of our new MEG task. Furthermore, the higher
      concordance from the picture verb generation task suggests that this is a
      promising task for use in the young clinical population.

PMID- 21195136
TI  - Immortalization and functional characterization of rat arachnoid cell lines.
AB  - Modeling the behavior of mammalian arachnoid cells is critical to understand
      hydrocephalus and other brain disorders involving abnormal flow of cerebrospinal
      fluid, yet relatively little is known about the physiology of arachnoid cells due
      to lack of a robust three-dimensional model system. Explanted primary cultures
      have been the only option to study transport across arachnoid cell membranes, but
      practical limitations of primary culture include slow growth, early senescence,
      and poor reproducibility. The purpose of this study was to create immortalized
      rat arachnoid cell lines to permit in vitro study of arachnoid granulations and
      properties of cerebrospinal fluid (CSF) flow. We established and partially
      characterized two immortalized cell lines generated from primary rat arachnoid
      cells, using retroviral gene transfer of SV40 large T antigen (SV40 LTAg) either
      with or without human telomerase (hTERT). The established cell lines stably
      express either SV40 LTAg alone, or SV40 LTAg and hTERT, and demonstrate high
      proliferative rate, contact inhibition at confluence, and stable expression of
      protein markers characteristic of native arachnoid cells over more than 160
      passages.

PMID- 21195137
TI  - Regulation of cytoskeleton machinery, neurogenesis and energy metabolism pathways
      in a rat gene-environment model of depression revealed by proteomic analysis.
AB  - The development of major depression requires both genetic and environmental
      factors. A brain proteomic investigation on the genetic model of Flinders
      sensitive and resistant line (FSL-FRL) rats was performed. Maternal separation
      (MS) was also applied to identify protein networks affected by stress exposure,
      since early-life trauma is considered an important antecedent of depression.
      Hippocampus (HIP) and prefrontal/frontal cortex proteins were extracted and
      separated by 2-Dimensional (2-D) gel electrophoresis. After image analysis,
      significantly modulated proteins in the different conditions analysed were
      identified by mass spectrometry. The expression of proteins involved in energy
      metabolism, cellular localization and transport, cytoskeleton organization and
      apoptosis differed in the two lines. Maternal separation differently affected the
      genetic backgrounds, by modulating cytoskeleton and neuron morphogenesis proteins
      in FSL; energy metabolism, cellular localization, neuron differentiation and
      intracellular transport in FRL. The present work shows that different mechanisms
      could be involved in the pathophysiology of depression and the vulnerability to
      stress, suggesting possible new cellular pathways and key markers for the study
      of affective disorders.

PMID- 21195138
TI  - Sub-cellular distribution of UNC-104(KIF1A) upon binding to adaptors as UNC
      16(JIP3), DNC-1(DCTN1/Glued) and SYD-2(Liprin-alpha) in C. elegans neurons.
AB  - The accumulation of cargo (tau, amyloid precursor protein, neurofilaments etc.)
      in neurons is a hallmark of various neurodegenerative diseases while we have only
      little knowledge how axonal transport is regulated. Kinesin-3 UNC-104(KIF1A) is
      the major transporter of synaptic vesicles and recent reports suggest that a
      cargo itself can affect the motor's activity. Inspecting an interactome map, we
      identify three putative UNC-104 interactors, namely UNC-16(JIP3), DNC
      1(DCTN1/Glued) and SYD-2(Liprin-alpha), known to be adaptors in essential
      neuronal protein complexes. We then employed the novel method bimolecular
      fluorescence complementation (BiFC) assay to visualize motor-adaptor complexes in
      the nervous system of living C. elegans. Interestingly, the binding of UNC-104 to
      each adaptor protein results in different sub-cellular distributions and has
      distinctive effects on the motor's motility. Specifically, if UNC-104 bound to
      UNC-16, the motor is primarily localized in the soma of neurons while bound to
      DNC-1, the motor is basically found in axonal termini. On the other hand, if UNC
      104 is bound to SYD-2 we identify motor populations mostly along axons.
      Therefore, these three adaptors inherit different functions in steering the motor
      to specific sub-cellular locations in the neuron.

PMID- 21195139
TI  - Ameliorative effect of traditional Japanese medicine yokukansan on age-related
      impairments of working memory and reversal learning in rats.
AB  - Aging is thought to impair prefrontal cortical (PFC) structure-sensitive
      cognitive functions and flexibility, such as working memory and reversal
      learning. A traditional Japanese medicine, yokukansan (YKS), is frequently used
      to treat age-related neurodegenerative disorders such as Alzheimer's disease in
      Japan, but its pharmacological properties have not been elucidated. The present
      study was designed to examine whether YKS improves age-related cognitive deficits
      using aged rats. YKS was administered to 21-month-old rats for 3 months. The
      ability to learn initially a reward rule for a T-maze discrimination task
      (initial learning) was examined in young control (4-month-old), aged control (24
      month-old) and YKS-treated aged (24-month-old) rats. Subsequently, working memory
      and reversal learning were examined in delayed alternation and reversal
      discrimination T-maze tasks, respectively. Locomotor activity was also measured
      in new environments. Although performance accuracy in the initial learning
      procedure did not differ among any experimental groups, accuracy in the delayed
      alternation task was significantly decreased in aged rats compared to young rats.
      Aged rats also showed significant decreases in accuracy in the reversal
      discrimination task. YKS treatment significantly ameliorated the age-related
      decreases in accuracy in the delayed alternation and reversal discrimination
      tasks. The ameliorative effects of YKS on impaired delayed alternation
      performance were reduced by intracranial infusions of a dopamine D1 receptor
      antagonist, SCH 23390, into the prelimbic cortical region of the PFC, and the YKS
      effects on impaired reversal learning were done by the infusions into the
      orbitofrontal cortex (OFC). Locomotor activity did not change in any experimental
      group. Thus, YKS ameliorated age-related impairments of working memory and
      reversal learning, which might be mediated by a dopaminergic mechanism in the PFC
      structure. These investigations provide information important for the treatment
      of brain dysfunctions in the elderly people.

PMID- 21195140
TI  - Gene recruitment--a common mechanism in the evolution of transfer RNA gene
      families.
AB  - The evolution of alloacceptor transfer RNAs (tRNAs) has been traditionally
      thought to occur vertically and reflect the evolution of the genetic code. Yet
      there have been several indications that a tRNA gene could evolve horizontally,
      from a copy of an alloacceptor tRNA gene in the same genome. Earlier, we provided
      the first unambiguous evidence for the occurrence of such "tRNA gene recruitment"
      in nature--in the mitochondrial (mt) genome of the demosponge Axinella corrugata.
      Yet the extent and the pattern of this process in the evolution of tRNA gene
      families remained unclear. Here we analyzed tRNA genes from 21 mt genomes of
      demosponges as well as nuclear genomes of rhesus macaque, chimpanzee and human.
      We found four new cases of alloacceptor tRNA gene recruitment in mt genomes and
      eleven cases in the nuclear genomes. In most of these cases we observed a single
      nucleotide substitution at the middle position of the anticodon, which resulted
      in the change of not only the tRNA's amino-acid identity but also the class of
      the amino-acyl tRNA synthetases (aaRSs) involved in amino-acylation. We
      hypothesize that the switch to a different class of aaRSs may have prevented the
      conflict between anticodon and amino-acid identities of recruited tRNAs. Overall
      our results suggest that gene recruitment is a common phenomenon in tRNA
      multigene family evolution and should be taken into consideration when tRNA
      evolutionary history is reconstructed.

PMID- 21195141
TI  - Global genome organization mediated by RNA polymerase III-transcribed genes in
      fission yeast.
AB  - Eukaryotic genomes exist as an elaborate three-dimensional structure in the
      nucleus. Recent studies have shown that this higher-order organization of the
      chromatin fiber is coupled to various nuclear processes including transcription.
      In fission yeast, we demonstrated that RNA polymerase III (Pol III)-transcribed
      genes such as tRNA and 5S rRNA genes, dispersed throughout chromosomal arm
      regions, localize to centromeres in interphase. This centromeric association of
      Pol III genes, mediated by the condensin complex, becomes prominent during
      mitosis. Here, we discuss potential roles of the Pol III gene-mediated genome
      organization during interphase and mitosis, and hypothesize that the interphase
      genome structure serves as a scaffold for the efficient assembly of condensed
      mitotic chromosomes and that tethering of chromosomal arm regions to centromeres
      allows chromosomes to properly segregate along the spindle microtubules during
      anaphase.

PMID- 21195142
TI  - The zebrafish genes encoding the Polycomb repressive complex (PRC) 1.
AB  - Polycomb repression controls regulation of hundreds of genes involved in
      development, signalling or cancer and is mediated by essentially two classes of
      chromatin-associated protein complexes, the Polycomb repressive complexes 1 and 2
      (PRC1 and PRC2). PRC2 trimethylates histone H3 at Lysine 27 and this H3K27me3
      epigenetic mark serves as a docking site for the PRC1 protein complex. Drosophila
      core PRC1 is composed of four subunits, Polycomb (Pc), Posterior sex combs (Psc),
      Polyhomeotic (Ph), and Sex combs extra (Sce). Each of these proteins has multiple
      orthologs in vertebrates. In particular, mammalian genomes encode five Pc family
      members (CBX2, 4, 6, 7 and 8), six Psc family members (BMI1, PCGF1, 2, 3, 5, and
      6), three Ph family members (PHC1, 2 and 3) and two Sce family members (RING1 and
      RNF2) generating an enormous scope for potential combinatorial diversity. In
      order to identify the corresponding PRC1 genes in zebrafish, homology searches
      were undertaken and allowed the identification of a total of 19 genes. Using
      phylogenetic, gene organization and gene location analyses, these genes were
      classified. The zebrafish genes encoding the PRC1 protein complex include 8 Pc
      orthologs (cbx2, cbx4, cbx6a, cbx6b, cbx7a, cbx7b, cbx8a and cbx8b), 6 Psc
      orthologs (bmi1a, bmi1b, pcgf1, pcgf5a, pcgf5b and pcgf6), 4 Ph orthologs (phc1,
      phc2a, phc2b and phc3) and a single Sce ortholog (rnf2). Our results indicate
      that the potentially high number of distinct PRC1 protein complexes generated by
      the components combinatorial appeared early in the vertebrate evolution. In
      addition to conserved gene organization and syntenies, transcript analyses
      revealed that transcriptional regulation leading to various isoforms syntheses is
      also conserved at genes encoding the PRC1 components, highlighting a possible
      important biological role of these isoforms.

PMID- 21195143
TI  - Neurotoxicological effects of low-dose methylmercury and mercuric chloride in
      developing offspring mice.
AB  - Mercury is a well-known toxic metal and potently induces severe
      neurotoxicological effects, especially in infants and children. The purpose of
      this study was to explore the underlying mechanisms of neurotoxic effects of
      mercurial compounds on the different stages of developing mice. Low-doses (the
      probability of human exposure in mercury-contaminated areas) of methylmercury
      (MeHg) (M, 0.02mg/kg/day) and mercury chloride (HgCl(2)) (H, 0.5mg/kg/day) were
      administered to mice of the following groups: (1) treatment with distilled water
      for 7 consecutive weeks after weaning (control-vehicle (CV)); exposure to
      mercurial compounds at different stages; (2) for 7 consecutive weeks after
      weaning (control-MeHg (CM) and control-HgCl(2) (CH)); (3) only during perinatal
      and weaning stages (MeHg-vehicle (MV) and HgCl-vehicle (HV)); and (4) in all
      experimental stages (MeHg-MeHg (MM) and HgCl(2)-HgCl(2) (HH)). Results revealed
      the neurobehavioral defects (increased locomotor activities, motor equilibrium
      impairment, and auditory dysfunction) that correlated with increasing Hg
      accumulation in CM and CH groups. However, it revealed a decrease and an increase
      in locomotor activities in MV and HV groups, respectively; these became more
      severe in MM and HH groups than in MV and HV groups. Motor equilibrium
      performance in MV and HV groups remained normal, while that in MM and HH groups
      was decreased. The most severe auditory defects (altered auditory brainstem
      response, ABR test) found in MM and HH groups than those in the respective CM and
      CH, MV and HV, including absolute wave III delays and interwave I-III latencies,
      which suggested that the irreversible auditory dysfunction caused by mercurial
      compounds. Furthermore, the alteration of lipid peroxidation (LPO), Na(+)/K(+)
      ATPase activities, and nitric oxide (NO(x)) in the brain tissues contributed to
      the observed neurobehavioral dysfunction and hearing impairment. These findings
      provide evidence that fetuses were much more susceptible to the effects of
      mercurial compounds with regard to inducing severely neurotoxicological injuries
      as that found in human beings. The signaling of ROS/Na(+)-K(+)-ATPase/NO(x) plays
      a crucial role in the underlying mechanism for mercurial compound-induced toxic
      effects in offspring.

PMID- 21195144
TI  - The critical period of valproate exposure to induce autistic symptoms in Sprague
      Dawley rats.
AB  - Prenatal exposure to valproic acid (VPA) induces neural tube defects and
      impairment in social behaviors related to autistic spectrum disorder in newborns,
      which make it a useful animal model of autism. In this study, we compared the
      effects of different time window of prenatal valproic acid exposure for inducing
      the altered social behaviors relevant to autism from embryonic day 7 to embryonic
      day 15 in Sprague-Dawley rats to determine the critical periods for the
      impairment. Compared to E7, E9.5 and E15 exposure, VPA exposure at E12 showed
      most significant changes in behaviors over control animals with reduced
      sociability and social preference. E9.5 exposure to valproic acid showed strong
      reproductive toxicity including decrease in the number of live birth. In general,
      exposure at E15 showed only marginal effects on reproduction and social
      behaviors. Finally, VPA-exposed rats at E12 were more sensitive to electric shock
      than VPA-exposed rats at any other periods. These results suggested that E12 is
      the critical period in rats when valproate exposure has prominent effects for
      inducing the altered social behavior similar to human autistic behavior.

PMID- 21195145
TI  - In vitro effects of acetylcholinesterase reactivators on monoamine oxidase
      activity.
AB  - Administration of acetylcholinesterase (AChE) reactivators (oximes) is usually
      used in order to counteract the poisoning effects of nerve agents. The
      possibility was suggested that oximes may show some therapeutic and/or adverse
      effects through their action in central nervous system. There are no sufficient
      data about interaction of oximes with monoaminergic neurotransmitter's systems in
      the brain. Oxime-type AChE reactivators pralidoxime, obidoxime, trimedoxime,
      methoxime and HI-6 were tested for their potential to affect the activity of
      monoamine oxidase of type A (MAO-A) and type B (MAO-B) in crude mitochondrial
      fraction of pig brains. The compounds were found to inhibit fully MAO-A with half
      maximal inhibitory concentration (IC(50)) of 0.375 mmol/l (pralidoxime), 1.53
      mmol/l (HI-6), 2.31 mmol/l (methoxime), 2.42 mmol/l (obidoxime) and 4.98 mmol/l
      (trimedoxime). Activity of MAO-B was fully inhibited by HI-6 and pralidoxime only
      with IC(50) 4.81 mmol/l and 11.01 mmol/l, respectively. Methoxime, obidoxime and
      trimedoxime displayed non-monotonic concentration dependent effect on MAO-B
      activity. Because oximes concentrations effective for MAO inhibition could not be
      achieved in vivo at the cerebral level, we suppose that oximes investigated do
      not interfere with brain MAO at therapeutically relevant concentrations.

PMID- 21195146
TI  - Estrogen-like effects of diet-derived cadmium differ from those of orally
      administered CdCl(2) in the ERE-luc estrogen reporter mouse model.
AB  - Cadmium (Cd), an environmental and dietary contaminant, has been described to
      mimic the effects of 17beta-estradiol (E(2)) in selected model systems when
      studied as an inorganic salt. However, inorganic Cd salts do not represent the
      main form of Cd exposure in general human populations. The aims of this study
      were to compare the estrogen-like effects and the bioavailability of dietary Cd
      to inorganic CdCl(2). Adult ovariectomized ERE-luc reporter mice were
      administered two bread based diets containing different concentrations of Cd
      (17.57 and 49.22MUg/kg, corresponding to oral intakes of 1.8 and 5.1MUg/kg body
      weight (bw) per day, respectively), inorganic CdCl(2) (1MUg/kg bw per day by
      gavage) or E(2) (5MUg/kg bw per day pellet) for 21 days. The effects on estrogen
      signaling were investigated by studying the uterine weights, luciferase
      activation, and expression of endogenous estrogen target genes. The uterine
      weight was significantly increased by both CdCl(2) and E(2) but not by the Cd
      containing diets. All treatments modulated the expression of luciferase and the
      endogenous estrogen target genes; however, there was no consistent overlap
      between the responses triggered by the bread diets and the responses stimulated
      by CdCl(2) or E(2). Oral exposure to Cd was calculated and the concentrations in
      liver and kidneys quantified to estimate the amount of absorbed Cd retained in
      tissues. The results suggest significantly lower absorption and/or tissue
      retention of dietary Cd compared to CdCl(2) following oral exposure. Altogether,
      our results support previous reports on in vivo estrogenicity of CdCl(2) but do
      not suggest the same activity for diet bound Cd. This study calls for caution
      when extrapolating results from pure compound studies (e.g. estrogenicity of
      CdCl(2)) to dietary exposure scenarios (e.g. estrogenicity of diet bound Cd).
      Further basic research is needed on the mechanisms of interaction between Cd and
      the estrogen signaling, biologically active species of Cd, and biomarkers of
      estrogen-like effects of Cd in vivo before human health risk assessment on the
      hormone disruptive effects of Cd can be carried out.

PMID- 21195147
TI  - Proteomic mapping of bezafibrate-treated human hepatocytes in primary culture
      using two-dimensional liquid chromatography.
AB  - Peroxisome proliferators have been extensively studied in rodents and are known
      to induce liver tumors, whereas the effects of these compounds are not very
      clearly identified in humans when they are widely exposed to herbicides,
      plasticizers, solvents or drugs such as the lipid-lowering fibrate bezafibrate
      (BEZA). We assessed the effect of BEZA on human hepatocyte proteome. Hepatocyte
      proteins, including those membrane-associated, were successfully extracted and
      separated using 2D-liquid chromatography (PF2D, Beckman coulter). Proteins that
      were regulated by >= 1.5 fold compared to controls were identified by mass
      spectrometry (MALDI-TOF, Bruker Daltonics) and SwissProt bank search. BEZA
      modified the expression of proteins involved in various metabolic pathways as
      well as in cell homeostasis. No marker of peroxisome proliferation was obtained
      but surprisingly the expression of proteins involved in liver carcinogenicity was
      modulated. The co-treatment of cultures with N-acetylcysteine modified the set of
      proteins regulated by BEZA, either by a potentiation or an inhibition of the
      effects. Our study points out that the hepatocellular redox environment has to be
      taken into account when using fibrates in therapeutics.

PMID- 21195148
TI  - Discriminating classes of developmental toxicants using gene expression profiling
      in the embryonic stem cell test.
AB  - The embryonic stem cell test (EST) has been shown to be a promising in vitro
      method for the prediction of developmental toxicity. In our previous studies, we
      demonstrated that the implementation of gene expression analysis in the EST may
      further improve the identification of developmental toxicants. In the present
      study, we investigated if gene expression profiling could be used to discriminate
      compound classes with distinct modes of action (MoA) using the EST protocol. Gene
      expression data of our previous study were used and were analyzed of embryonic
      stem cell (ESC) differentiation cultures exposed to six compounds belonging to
      two classes with distinct MoA, namely phthalates and triazoles. We used three
      approaches to study class-characteristic gene regulation that may be useful for
      discrimination of compound classes. First, at the individual gene level, gene
      signatures characteristic for each class were identified that successfully
      discriminated both classes using principal component analysis. Second, at the
      functional level, enriched gene ontology (GO) biological processes showed their
      usefulness for class discrimination via hierarchical clustering. Third, two
      previously identified gene sets, which we designed to predict developmental
      toxicity, appeared successful in separating phthalate from triazole compounds. In
      summary, we established the possibility to discriminate between compound classes
      in the EST system using three different specific transcriptomics-based
      approaches. Differential gene expression information specific for the class of
      compound under study may be employed to optimize prioritization of compounds
      within that class for further testing.

PMID- 21195149
TI  - Furazolidone induced oxidative DNA damage via up-regulating ROS that caused cell
      cycle arrest in human hepatoma G2 cells.
AB  - Furazolidone (FZD) is an antimicrobial agent that has been shown to have
      mutagenic, genotoxic and potentially carcinogenic properties when tested in a
      variety of systems in vitro and in vivo. In this study, we investigated FZD's DNA
      damaging effect in human hepatoma cells aiming at further defining the molecular
      mechanism of FZD's cytotoxicity. Addition of FZD resulted in cell growth
      suppression and cell cycle arrest in S phase accompanied by remarkable DNA strand
      breaks with increased levels of intracellular reactive oxygen species (ROS) and 8
      hydroxydeoxyguanosine. Activities of antioxidases were down-regulated following
      FZD treatment and antioxidant agent catalase and superoxide dismutase ameliorated
      FZD's DNA damaging effects. Moreover, FZD caused much more extensive damage to
      mitochondrial DNA (mtDNA) than to nuclear DNA for which the decrease in mtDNA
      content correlated with FZD usage in a dose-dependent manner. However, there was
      no evidence of FZD induced mtDNA mutation in the mitochondrial DNA displacement
      loop. These results demonstrate that FZD up-regulates the production of
      intracellular ROS to cause oxidative DNA damage with mtDNA being the most
      vulnerable targets. Oxidative stress and the injury of mtDNA could be early
      indicators of FZD-induced cytotoxicity, with the resulting abnormal progression
      of the cell cycle.

PMID- 21195151
TI  - Up-regulation of Fas/FasL activation contribute to the apoptosis enhancement of
      RU486 by Gong-Qing Decoction, a traditional Chinese prescription.
AB  - AIM OF THE STUDY: To elucidate the mechanisms of Gong Qing Decoction(GQD) on
      human trephocytes and decidual cells in vivo based upon the effective practice of
      alleviating uterine bleeding in RU486 medical abortion. MATERIALS AND METHODS: 90
      intrauterine pregnancy women within 7 weeks, presenting for elective termination
      of pregnancy, were divided into the GQD-RU486 group, the RU486 group and the
      vacuum aspiration group. Duration of uterine bleeding was recorded and volume of
      uterine bleeding was measured by the method of alkaline hematin photometric.
      Ultramicrostructure of trephocytes and decidual cells were observed with
      transmission electron microscope (TEM), and apoptosis rate (AR) was assessed by
      terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL)
      assay. At the same time, immunohistochemical staining was performed and integral
      optical density was analyzed to evaluate the protein expression of Fas, FasL,
      Caspase-8 and Caspase-3 in both trephocytes and decidual cells preliminarily.
      RESULTS: In comparison with the RU486 group and the vacuum aspiration group, both
      the duration and volume of uterine bleeding decreased significantly in the GQD
      RU486 group. At the same time, both trephocytes and decidual cells in the GQD
      RU486 group showed typical character of apoptotic ultramicrostructure and
      displayed up-regulated apoptosis rate. Synchronously, the integral optical
      density showed increased protein expression of Fas, FasL, Caspase-8 and Caspase-3
      in both trephocytes and decidual cells in the GQD-RU486 group compared with other
      groups. CONCLUSION: These data suggest that GQD can alleviate uterine bleeding
      effectively in RU486 medical abortion by way of apoptosis induction. The
      apoptosis enhancement of RU486 by GQD may be attributable to the activation of
      Fas and FasL.

PMID- 21195150
TI  - Cholinergic cells of the pontomesencephalic tegmentum: connections with auditory
      structures from cochlear nucleus to cortex.
AB  - Acetylcholine (ACh) is a neuromodulator that is likely to play a role in
      plasticity as well as other phenomena at many sites in the auditory system. The
      auditory cortex receives cholinergic innervation from the basal forebrain,
      whereas the cochlea receives cholinergic innervation from the superior olivary
      complex. Much of the remainder of the auditory pathways receives innervation from
      the pedunculopontine and laterodorsal tegmental nuclei, two nuclei referred to
      collectively as the pontomesencephalic tegmentum (PMT). The PMT provides the
      major source of ACh to the auditory thalamus and the midbrain, and is a
      substantial source (in addition to the superior olivary complex) of ACh in the
      cochlear nucleus. Individual cholinergic cells in the PMT often have axon
      branches that innervate multiple auditory nuclei, including nuclei on both sides
      of the brain as well as nuclei at multiple levels of the auditory system. The
      auditory cortex has direct axonal projections to the PMT cells, including
      cholinergic cells that project to the inferior colliculus or cochlear nucleus.
      The divergent projections of PMT cholinergic cells suggest widespread effects on
      the auditory pathways. These effects are likely to include plasticity as well as
      novelty detection, sensory gating, reward behavior, arousal and attention.
      Descending projections from the forebrain, including the auditory cortex, are
      likely to provide a high level of cognitive input to these cholinergic effects.
      Dysfunction associated with the cholinergic system may play a role in disorders
      such as tinnitus and schizophrenia.

PMID- 21195152
TI  - Hepatoprotection of Graptopetalum paraguayense E. Walther on CCl4-induced liver
      damage and inflammation.
AB  - AIM OF THIS STUDY: Graptopetalum paraguayense E. Walther, a vegetable consumed in
      Taiwan, has been used in folk medicine for protection against liver injury,
      although its actual efficacy remains uncertain. Therefore, we investigated the
      protective effects of Graptopetalum paraguayense E. Walther against carbon
      tetrachloride (CCl(4))-induced liver damage in rats. MATERIALS AND METHODS: Water
      extracts of Graptopetalum paraguayense E. Walther (WGP) were administered for 8
      consecutive weeks to male Sprague-Dawley rats. And a dose-dependent manner in
      preventing liver damage was confirmed. Moreover, the major ingredient of WGP,
      gallic acid, was also orally administrated in the CCl(4)-induced rats. The
      hepatoprotective activity was assessed using various biochemical parameters such
      as antioxidant enzymes and histopathological studies. RESULTS: WGP ranging from
      50 to 300 mg/kg bw administrations significantly lowered serum aspartate
      transaminase (AST) and alanine transaminase (ALT) levels, and inhibited
      malondialdehyde (MDA) generation in CCl(4)-treated rats. WGP increased cellular
      GSH level and antioxidant enzymes, including superoxide dismutase, glutathione
      reductase, and catalase. Serum tumor necrosis factor-alpha (TNF-alpha) was
      decreased in the group treated with CCl(4) plus WGP (150 and 300 mg/kg bw).
      Histopathological examination of livers showed that WGP reduced fatty
      degeneration, cytoplasmic vacuolization and necrosis in CCl(4)-treated rats. In
      contrary, 10mg/kg bw of gallic acid was administrated, this dose was related with
      WGP (300 mg/kg bw), and had significantly decreased the AST and ALT compared to
      the CCl(4)-treated group. Aforesaid results suggested that gallic acid from WGP
      offered antioxidative activity against CCl(4)-induced oxidative liver damage.
      CONCLUSIONS: Taken together, this study is the first time to suggest that
      Graptopetalum paraguayense E. Walther exerts hepatoprotection via promoting
      antioxidative and anti-inflammatory properties against CCl(4)-induced oxidative
      liver damage.

PMID- 21195153
TI  - The effects of Boehmeria nivea (L.) Gaud. on embryonic development: in vivo and
      in vitro studies.
AB  - AIM OF THE STUDY: Boehmeria nivea (L.) Gaud. was commonly used to treat
      miscarriages clinically. The aim of this study was to examine its safety for
      embryonic development. MATERIALS AND METHODS: Pregnant mice were randomly
      assigned into 5 groups, i.e. mice were oral-treated with distilled water (G1),
      with Boehmeria nivea extract of 2, 8 or 32 g/kg/day (G2, G3 or G4), and with 3
      doses of vitamin A of 200,000 IU/kg as positive controls (G5). Meanwhile, IC(50)
      values for both embryonic stem cells (ESCs) and 3T3 cells were detected by
      cytotoxicity assays. RESULTS: (1) The resorptions and malformed fetuses in G5
      were significantly higher than G1 (P<0.001), whereas the maternal body-weight and
      uterus-weight were lower than G1 (P<0.05); (2) there was no difference in the
      fetal body-weight, maternal relative body-weight gain, liver-, kidney- or heart
      weight, relative organ-weight, and histological examination among five groups;
      (3) there was no difference in IC(50) values between ESCs and 3T3 cells, but high
      concentration of Boehmeria nivea extract might significantly lower ESCs'
      viability (P<0.05). CONCLUSION: Boehmeria nivea extract at 32 g/kg/day did not
      cause significant embryotoxicity or maternal toxicity in mice, although it might
      cause cytotoxicity in cultured ESCs at a high dose.

PMID- 21195154
TI  - Traditional Chinese formula, lubricating gut pill, stimulates cAMP-dependent CI(
      ) secretion across rat distal colonic mucosa.
AB  - AIM OF THE STUDY: Lubricating gut pill (LGP), a traditional Chinese formula, had
      been conformed to improve the loperamide-induced rat constipation by stimulation
      of Cl(-) secretion, but its mechanism has not been fully explored. Thus, the
      purpose of this study was to identify the action sites of LGP-stimulated Cl(-)
      secretion across rat distal colonic mucosa. MATERIALS AND METHODS: Rat distal
      colonic mucosa was mounted in Ussing chambers and short circuit current (I(SC)),
      apical Cl(-) current and basolateral K(+) current were recorded. Intracellular
      cyclic adenosine monophosphate (cAMP) content and protein kinase A (PKA) activity
      were determined with ELISA kit and the non-radioactive PepTag test, respectively.
      RESULTS: LGP at 800MUg/ml elicited a sustained increase in Cl(-) secretory
      response, which was inhibited by CFTR(inh)172, a cystic fibrosis transmembrane
      conductance regulator (CFTR) inhibitor. Permeabilizing apical membrane with
      nystatin revealed that LGP-stimulated basolateral K(+) current was significantly
      inhibited by KCNQ1 K(+) channel inhibitor chromanol 293B. LGP-stimulated I(SC)
      was markedly reduced by pretreatment with cis-N-[2-phenylcyclopentyl]
      azacyclotridec-1-en-2amine (MDL-12,330A) and N-[2-(p-bromocinnamylamino)ethyl]-5
      isoquinolinesulfonamide (H-89), but not with inhibitors of Ca(2+)-dependent
      signaling pathway. Treatment of tissue with LGP resulted in an increase in
      intracellular cAMP level and the activation in protein kinase A. The E
      prostanoid(4) (EP)(4) receptor antagonist L-161,982 completely eliminated LGP
      induced response. CONCLUSIONS: The results showed that LGP enhances Cl(-) and
      fluid secretion via prostanoid receptor signaling and also cAMP and protein
      kinase A pathway, subsequently triggering the activation of apical Cl(-) channels
      mostly CFTR and basolateral cAMP-dependent K(+) channel.

PMID- 21195155
TI  - Polygalae radix inhibits toxin-induced neuronal death in the Parkinson's disease
      models.
AB  - AIM OF THE STUDY: Polygalae radix, the root of Polygala tenuifolia Willd, has
      commonly been used for the treatment of amnesia and anxiety in traditional Korean
      medicine. The aim of this study was to investigate its neuroprotective effects
      and possible mechanisms of action in models of Parkinson's disease. MATERIALS AND
      METHODS: This study utilized a 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay, a reactive oxygen species (ROS) assay, a
      nitric oxide (NO) production assay, and a caspase-3 activity test as measures of
      cell viability in PC12 cells damaged by 6-hydroxydopamine (6-OHDA). The
      protective effects of PRE against 1-methyl-4-phenylpyridium (MPP(+))-induced
      neurotoxicity were assessed in rat primary dopaminergic neurons and in a mouse PD
      model in which PRE was administered (100mg/kg/day, 3 days, p.o.) before acute 1
      mehtyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity. Finally, TH
      immunohistochemistry tests were conducted in the substantia nigra pars compacta
      (SNpc) and striatum (ST). RESULTS AND CONCLUSIONS: PRE significantly inhibited 6
      OHDA-induced cell damage at doses of 0.05-1MUg/ml with a maximal effect at
      0.1MUg/ml. Caspase-3 activity and the production of ROS and NO were alleviated at
      0.1MUg/ml. Also at this dose, PRE protected mesencephalic dopaminergic neurons
      from MPP(+)-induced toxicity. In an in vivo mouse model of PD, PRE protected
      dopaminergic neurons and fibers from MPTP-induced toxicity in the SNpc and ST.
      These results demonstrate that PRE has protective effects on dopaminergic neurons
      via its anti-oxidant and anti-apoptotic activity.

PMID- 21195156
TI  - Chlamydia abortus YhbZ, a truncated Obg family GTPase, associates with the
      Escherichia coli large ribosomal subunit.
AB  - The stringent stress response is vital for bacterial survival under adverse
      environmental conditions. Obligate intracellular Chlamydia lack key stringent
      response proteins, but nevertheless can interrupt the cell cycle and enter stasis
      or persistence upon amino acid starvation. A possible key protein retained is
      YhbZ, a homologue of the ObgE guanosine triphosphatase (GTPase) superfamily
      connecting the stringent stress response to ribosome maturation. Curiously,
      chlamydial YhbZ lacks the ObgE C-terminal domain thought to be essential for
      binding the large ribosomal subunit. We expressed recombinant Chlamydia abortus
      YhbZ and showed it to be a functional GTPase, with similar activity to other Obg
      GTPase family members. As Chlamydia are resistant to genetic manipulation, we
      performed heterologous expression and gradient centrifugation experiments in
      Escherichia coli and found that, despite the missing C-terminal domain, C.
      abortus YhbZ co-fractionates with the E. coli 50S large ribosomal subunit. In
      addition, overexpression of chlamydial YhbZ in E. coli leads to growth defects
      and elongation, as reported for other Obg members. YhbZ did not complement an E.
      coli obgE temperature-sensitive mutant, indicating the C-terminal acidic domain
      may have an additional role. This data supports a role for YhbZ linking the
      chlamydial stress response to ribosome function and cellular growth.

PMID- 21195157
TI  - Antibacterial activity of a synthetic peptide that mimics the LPS binding domain
      of Indian mud crab, Scylla serrata anti-lipopolysaccharide factor (SsALF) also
      involved in the modulation of vaginal immune functions through NF-kB signaling.
AB  - Recently the cDNA coding for anti-lipopolysaccharide factor (ALF) has been
      identified from the Indian mud crab, Scylla serrata and has been named S. serrata
      anti-lipopolysaccharide factor (SsALF). SsALF protein sequence demonstrated the
      presence of two highly conserved cystine residues between which the putative
      lipopolysaccharide (LPS) binding domain is known to be located. In this study, we
      have designed and synthesized a 24 amino acid linear (lSsALF24) and a cyclic
      (cSsALF24) peptides based on this putative LPS binding domain and demonstrated
      the ability of these peptides to bind to LPS. The peptides were active against
      vaginal pathogens demonstrated by MIC, CFU and phagocytosis assays. cSsALF24 did
      not show toxicity to human vaginal epithelial cells (HeLa-S3), macrophages and
      rabbit erythrocytes even at high concentration (64.64 MUM). Flow cytometry
      results demonstrated that cSsALF24 peptide suppressed LPS induced phagocytosis of
      FITC labeled E. coli. HeLa cells were stimulated with LPS (10 MUg/ml) alone for 6
      h or after two washings with PBS, treated for 1 h with cSsALF24 (64.64 MUM).
      After washing, the cells were cultured for 24 h in fresh media. The spent media
      as well as cells were collected for the determination of cytokine/chemokine
      levels such as interleukin-6 (IL-6) interleukin-8 (IL-8), monocyte chemotactic
      protein-1 (MCP-1) and interleukin-1alpha (IL-1alpha) using ELISA and RT-PCR
      respectively. Similar results were obtained with LPS stimulated cells treated
      with c/nSsALF24 or unstimulated cells treated with c/nSsALF24. The expression of
      cytokine/chemokines and mRNA's coding these proteins were unaffected in
      c/nSsALF24 treated cells. In contrast, in LPS stimulated cells, the expression
      levels of these molecules were up-regulated via the induction of nuclear factor
      kappa-B (NF-kB) levels. However, the expression of these pro-inflammatory markers
      was decreased in LPS stimulated cells following the treatment with cSsALF24,
      attributing anti-inflammatory potential of the peptide. Collectively, these
      findings suggest that cSsALF24 might regulate the vaginal epithelial cell immune
      responses indirectly through modulation of LPS-TLR4 binding in NF-kB pathway.

PMID- 21195158
TI  - Chrysin promotes tumor necrosis factor (TNF)-related apoptosis-inducing ligand
      (TRAIL) induced apoptosis in human cancer cell lines.
AB  - Chrysin exists widely in plants, honey and propolis. The anti-cancer property of
      chrysin has been demonstrated though the molecular mechanism is not clear. In
      this study, we found that pre-treatment with chrysin could promote the cell death
      induced by TRAIL according to the morphological changes and appearance of sub-G1
      peak in four human cancer cell lines. In HCT-116 cells, the results of flow
      cytometry analysis showed that the percentage of sub-G1 reached (38.89 +/- 3.78)
      % when pre-treatment of chrysin was used at 40 MUM, but that was only (2.53 +/-
      0.10) % in the untreated group and (13.22 +/- 0.20) % in TRAIL alone group. The
      differences between the combination and the untreated or TRAIL alone group were
      all significant (P<0.05) and dose-dependent effect was obvious. Similar results
      were obtained in CNE1 cells. In the search of molecular mechanisms, we found that
      pre-treatment with chrysin could increase TRAIL-induced degradation of caspase 3,
      caspase 8, PARP proteins. Z-VAD-fmk, which is a pan-caspase inhibitor, could
      inhibit the apoptosis enhanced by the combination of chrysin and TRAIL. All data
      indicate that chrysin can enhance the apoptosis induced by TRAIL, and the
      apoptosis is caspase-dependent and related to the activation of caspase 8.

PMID- 21195159
TI  - L-cysteine as a regulator for arsenic-mediated cancer-promoting and anti-cancer
      effects.
AB  - Previous studies have shown that activities of tyrosine kinases and secretion of
      the active form of matrix metalloproteinase-2 (MMP-2) are correlated with
      promotion of tumor growth, while apoptotic cell death in cancer cells is
      correlated with anti-cancer effects. Although arsenic has been reported to have
      both cancer-promoting and anti-cancer effects, the mechanisms of the arsenic
      mediated bidirectional effects remain unknown. We examined the effects of arsenic
      on both proto-oncogene c-RET-transfected NIH3T3 cells with benign characters and
      oncogenic RET-MEN2A-transfected NIH3T3 cells with malignant characters. Arsenic
      promoted not only c-RET tyrosine kinase activity but also genetically activated
      RET-MEN2A kinase activity with promotion of dimer formation of RET proteins.
      Arsenic also increased secretion of the active form of MMP-2 in both RET-MEN2A
      transfectants and c-RET-transfectants. On the other hand, arsenic promoted poly
      (ADP-ribose) polymerase (PARP) degradation and cell death in both malignant and
      non-malignant cells. Interestingly, l-cysteine inhibited the arsenic-mediated
      tumor-promoting effects (activation of kinases and MMP-2 secretion) but not
      arsenic-mediated anti-cancer effects (PARP degradation and cell death). Our
      results suggest redox-linked regulation of arsenic-mediated activities of kinases
      and MMP-2 secretion but not arsenic-mediated cell death. Our results also suggest
      that l-cysteine is an ideal supplement that inhibits arsenic-mediated tumor
      promoting effects without affecting arsenic-mediated anti-cancer effects.

PMID- 21195160
TI  - The intra- and inter-laboratory reproducibility and predictivity of the
      KeratinoSens assay to predict skin sensitizers in vitro: results of a ring-study
      in five laboratories.
AB  - Due to regulatory constraints and ethical considerations, research on
      alternatives to animal testing to predict the skin sensitization potential of
      novel chemicals has gained a high priority. Accordingly, different in vitro, in
      silico and in chemico approaches have been described in the scientific literature
      to achieve this goal. To replace regulatory approved animal tests, these
      alternatives need to be transferable to other labs, their within and between
      laboratory reproducibility must be assured, and their predictivity should be
      high. The KeratinoSens assay is a cell-based reporter gene assay to screen
      substances with a full dose-response assessment. It is based on a stable
      transgenic keratinocyte cell line. The induction of a luciferase gene under the
      control of the antioxidant response element (ARE) derived from the human AKR1C2
      gene is determined. Here we report on the results of a ring-study with five
      laboratories performing the KeratinoSens assay on a set of 28 test substances.
      The assay was found to be easily transferable to all laboratories. Overall both
      the qualitative (sensitizer/non-sensitizer categorization) and the quantitative
      (concentration for significant gene induction) results were reproducible between
      laboratories. A detailed analysis of the transferability, the within- and between
      laboratory reproducibility and the predictivity is presented.

PMID- 21195162
TI  - Characterization of microsatellite loci in the SLA class I region.
AB  - Microsatellite (MS) markers in the SLA-1 region were characterized via sequencing
      analysis with BAC clones generated from the National Institute of Health
      miniature pigs (MIPs). A total of 16 BAC clones were sequenced producing 15,228
      shotgun reads, corresponding to 11.2 X sequencing coverage, that were used to
      construct a contig of 12.18 Mb in length. MS markers were compared with
      previously deposited GenBank sequences to verify the existence of 423 potential
      MS candidate markers in the SLA-1 region. Evaluation of these polymorphisms
      confirmed 59 markers in MIPs, and the combined data including sequences from
      GenBank revealed 155 polymorphic MS markers. MS markers identified from this
      analysis can be used to provide an alternative method to direct typing for
      determining an individual's SLA-1 haplotype.

PMID- 21195161
TI  - Cross-species Functionome analysis identifies proteins associated with DNA
      repair, translation and aerobic respiration as conserved modulators of UV
      toxicity.
AB  - Cellular responses to DNA damage can prevent mutations and death. In this study,
      we have used high throughput screens and developed a comparative genomic
      approach, termed Functionome mapping, to discover conserved responses to UVC
      damage. Functionome mapping uses gene ontology (GO) information to link proteins
      with similar biological functions from different organisms, and we have used it
      to compare 303, 311 and 288 UVC-toxicity modulating proteins from Escherichia
      coli, Schizosaccharomyces pombe and Saccharomyces cerevisiae, respectively. We
      have demonstrated that all three organisms use DNA repair, translation and
      aerobic respiration associated processes to modulate the toxicity of UVC, with
      these last two categories highlighting the importance of ribosomal proteins and
      electron transport machinery. Our study has demonstrated that comparative genomic
      approaches can be used to identify conserved responses to damage, and suggest
      roles for translational machinery and components of energy metabolism in
      optimizing the DNA damage response.

PMID- 21195163
TI  - Analysis of global methylation using a Zta-expressing nasopharyngeal carcinoma
      cell line.
AB  - EBV infects more than 90% of the human population and persists in most
      individuals as a latent infection where the viral genome is silenced by host
      driven methylation. The lytic cycle is initiated when the viral protein Zta binds
      to methylated BRLF1 and BRRF1 promoters. Although studies reveal the role of Zta
      and methylation changes in the viral genome upon EBV infection to reactivation,
      whether Zta plays any role in alteration of methylation in the host genome
      remains unknown. Using an inducible model, we demonstrate that global DNA
      methylation, based on whole-genome 5-methylcytosine content, and regional DNA
      methylation in repetitive elements, imprinting genes and the X chromosome,
      remains unchanged in response to Zta expression. Expression of DNA
      methyltransferases was also unaffected by ectopically expressed Zta. Our data
      imply that alteration of host gene expression following EBV reactivation may
      reflect methylation-independent Zta-mediated gene activation and not epigenetic
      modification of the host genome.

PMID- 21195164
TI  - Transcriptional control of maladaptive and protective responses in alcoholics: a
      role of the NF-kappaB system.
AB  - Alcohol dependence and associated cognitive impairment appear to result from
      maladaptive neuroplasticity in response to chronic alcohol consumption,
      neuroinflammation and neurodegeneration. The inherent stability of behavioral
      alterations associated with the addicted state suggests that transcriptional and
      epigenetic mechanisms are operative. NF-kappaB transcription factors are
      regulators of synaptic plasticity and inflammation, and responsive to a variety
      of stimuli including alcohol. These factors are abundant in the brain where they
      have diverse functions that depend on the composition of the NF-kappaB complex
      and cellular context. In neuron cell bodies, NF-kappaB is constitutively active,
      and involved in neuronal injury and neuroprotection. However, at the synapse, NF
      kappaB is present in a latent form and upon activation is transported to the cell
      nucleus. In glia, NF-kappaB is inducible and regulates inflammatory processes
      that exacerbate alcohol-induced neurodegeneration. Animal studies demonstrate
      that acute alcohol exposure transiently activates NF-kappaB, which induces
      neuroinflammatory responses and neurodegeneration. Postmortem studies of brains
      of human alcoholics suggest that repeated cycles of alcohol consumption and
      withdrawal cause adaptive changes in the NF-kappaB system that may permit the
      system to better tolerate excessive stimulation. This type of tolerance, ensuring
      a low degree of responsiveness to applied stimuli, apparently differs from that
      in the immune system, and may represent a compensatory response that protects
      brain cells against alcohol neurotoxicity. This view is supported by findings
      showing preferential downregulation of pro-apoptotic gene expression in the
      affected brain areas in human alcoholics. Although further verification is
      needed, we speculate that NF-kappaB-driven neuroinflammation and disruption to
      neuroplasticity play a significant role in regulating alcohol dependence and
      cognitive impairment.

PMID- 21195165
TI  - Targeting the hematopoietic system for the treatment of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most prevalent cause of dementia in humans. This
      disease is characterized by the presence of amyloid beta (Ab) deposits in the
      parenchyma (also known as amyloid plaques or senile plaques) and in the cerebral
      vasculature. Though Ab formation and deposits are strongly correlated with
      cognitive impairment, the mechanisms responsible for the synaptic dysfunctions
      and loss of neurons in AD remain largely unknown. Many studies have provided
      evidence that microglial cells are attracted to amyloid deposits both in human
      samples and in rodent transgenic models that develop this disease. We have
      recently found that blood-derived microglia and not their resident counterparts
      have the ability to eliminate amyloid deposits by a cell-specific phagocytic
      mechanism. These bone marrow-derived microglia have consequently a great
      therapeutic potential for AD patients. Molecular strategies aiming to improve
      their recruitment could lead to a new powerful tool for the elimination of toxic
      Ab and improve cognitive functions. However, numerous limitations have to be
      taken into consideration before recommending such a cellular therapy and these
      are discussed in the present review.

PMID- 21195167
TI  - Oxidative stress, chronic inflammation, and telomere length in patients with
      periodontitis.
AB  - The aim of this study was to determine leukocyte telomere length (LTL) in
      individuals with periodontitis and controls, exploring its relationship with
      systemic inflammation and oxidative stress. Five hundred sixty-three participants
      were recruited for this case-control study: 356 subjects with and 207 subjects
      without periodontitis. LTL was measured by a qPCR technique from leukocytes' DNA.
      Global measures of oxidative stress (reactive oxygen metabolites) and biological
      antioxidant potential in plasma were performed together with high-sensitivity
      assays for C-reactive protein (CRP). Leukocyte counts and lipid profiles were
      performed using standard biochemistry. Cases had higher levels of CRP (2.1+/
      3.7mg/L vs 1.3+/-5.4mg/L, P<0.001) and reactive oxygen metabolites (378.1+/-121.1
      U Carr vs 277.4+/-108.6 U Carr, P<0.001) compared to controls. Overall, cases had
      shorter LTL with respect to controls (1.23+/-0.42 vs 1.12+/-0.31T/S ratio,
      P=0.006), independent of age, gender, ethnicity, and smoking habit. When divided
      by subgroup of periodontal diagnosis (chronic, n=285; aggressive, n=71), only
      chronic cases displayed shorter LTL (P=0.01). LTL was negatively correlated with
      age (P=0.001; R=-0.2), oxidative stress (P=0.008; R=-0.2), and severity of
      periodontitis (P=0.003; R=-0.2) in both the whole population and the subgroups
      (cases and controls). We conclude that shorter telomere lengths are associated
      with a diagnosis of periodontitis and their measures correlate with the oxidative
      stress and severity of disease.

PMID- 21195166
TI  - Activation of the maternal immune system induces endocrine changes in the
      placenta via IL-6.
AB  - Activation of the maternal immune system in rodent models sets in motion a
      cascade of molecular pathways that ultimately result in autism- and schizophrenia
      related behaviors in offspring. The finding that interleukin-6 (IL-6) is a
      crucial mediator of these effects led us to examine the mechanism by which this
      cytokine influences fetal development in vivo. Here we focus on the placenta as
      the site of direct interaction between mother and fetus and as a principal
      modulator of fetal development. We find that maternal immune activation (MIA)
      with a viral mimic, synthetic double-stranded RNA (poly(I:C)), increases IL-6
      mRNA as well as maternally-derived IL-6 protein in the placenta. Placentas from
      MIA mothers exhibit increases in CD69+ decidual macrophages, granulocytes and
      uterine NK cells, indicating elevated early immune activation. Maternally-derived
      IL-6 mediates activation of the JAK/STAT3 pathway specifically in the
      spongiotrophoblast layer of the placenta, which results in expression of acute
      phase genes. Importantly, this parallels an IL-6-dependent disruption of the
      growth hormone-insulin-like growth factor (GH-IGF) axis that is characterized by
      decreased GH, IGFI and IGFBP3 levels. In addition, we observe an IL-6-dependent
      induction in pro-lactin-like protein-K (PLP-K) expression as well as MIA-related
      alterations in other placental endocrine factors. Together, these IL-6-mediated
      effects of MIA on the placenta represent an indirect mechanism by which MIA can
      alter fetal development.

PMID- 21195168
TI  - Natural compounds containing a catechol group enhance the formation of Nepsilon
      (carboxymethyl)lysine of the Maillard reaction.
AB  - Inhibition of advanced glycation end-product (AGE) formation is a potential
      strategy for the prevention of clinical diabetes complications. Screening for new
      AGE inhibitors revealed several natural compounds that inhibited the formation of
      N(epsilon)-(carboxymethyl)lysine (CML), a major antigenic AGE structure, whereas
      natural compounds containing a catechol group, such as gallic acid and
      epicatechin, significantly enhanced CML formation. A similar enhancing effect was
      also observed by culturing THP-1 macrophages in the presence of catechol
      compounds. Although 4-methylcatechol significantly enhanced CML formation from
      glycated HSA (gHSA), a model for Amadori proteins, analogues of catechol such as
      5-methylresorcinol and methylhydroquinone showed no enhancing effect. Even though
      1mM 4-methylcatechol, epicatechin, and gallic acid significantly enhanced CML
      formation from gHSA, it was significantly inhibited by decreasing their
      concentration. The enhancing effect of 1mM catechol compounds was inhibited in
      the presence of the glutathione peroxidase system, thus demonstrating that
      hydrogen peroxide generated from catechol compounds plays an important role in
      the enhancement of CML formation. Furthermore, administration of 500mg/kg/day
      epicatechin to STZ-induced diabetic mice for 45days enhanced CML accumulation at
      the surface area of gastric epithelial cells in the stomach. This study provides
      the first evidence that high amounts of catechol-containing structures enhance
      oxidative stress, thus leading to enhanced CML formation, and this phenomenon may
      explain the paradoxical effect that some flavonoids have on redox status.

PMID- 21195169
TI  - Cadmium induction of reactive oxygen species activates the mTOR pathway, leading
      to neuronal cell death.
AB  - Cadmium (Cd), a highly toxic environmental pollutant, induces neurodegenerative
      diseases. Recently we have demonstrated that Cd induces neuronal apoptosis in
      part through activation of the mammalian target of rapamycin (mTOR) pathway.
      However, the underlying mechanism is unknown. Here we show that Cd induces the
      generation of reactive oxygen species (ROS) by upregulating the expression of
      NADPH oxidase 2 and its regulatory proteins (p22(phox), p67(phox), p40(phox),
      p47(phox), and Rac1) in PC12 and SH-SY5Y cells. Cd induction of ROS contributed
      to the activation of mTOR signaling, as pretreatment with N-acetyl-l-cysteine
      (NAC), a ROS scavenger, prevented this event. Further studies reveal that Cd
      induction of ROS increased phosphorylation of the type I insulin-like growth
      factor receptor (IGFR) beta subunit, which was abrogated by NAC. Wortmannin, a
      phosphoinositide 3'-kinase (PI3K) inhibitor, partially attenuated Cd-induced
      phosphorylation of Akt, p70 S6 kinase 1, and eukaryotic initiation factor 4E
      binding protein 1, as well as apoptosis of the neuronal cells. In addition,
      overexpression of wild-type phosphatase and tensin homologue deleted on
      chromosome 10 (PTEN) or pretreatment with aminoimidazole carboxamide
      ribonucleotide, an AMP-activated protein kinase (AMPK) activator, partially
      prevented Cd-induced ROS and activation of the mTOR pathway, as well as cell
      death. The results indicate that Cd induction of ROS activates mTOR signaling,
      leading to neuronal cell death, in part by activating the positive regulators
      IGFR/PI3K and by inhibiting the negative regulators PTEN/AMPK. The findings
      suggest that inhibitors of PI3K and mTOR, activators of AMPK, or antioxidants may
      be exploited for the prevention of Cd-induced neurodegenerative diseases.

PMID- 21195171
TI  - A possible application of magnetic resonance imaging for pharmaceutical research.
AB  - Magnetic resonance imaging (MRI) is a non-destructive and non-invasive method,
      the experiment can be conducted in situ and allows the studying of the sample and
      the different processes in vitro or in vivo. 1D, 2D or 3D imaging can be
      undertaken. MRI is nowadays most widely used in medicine as a clinical diagnostic
      tool, but has still seen limited application in the food and pharmaceutical
      sciences. The different imaging pulse sequences of MRI allow to image the
      processes that take place in a wide scale range from ms (dissolution of compact
      tablets) to hours (hydration of drug delivery systems) for mobile as well as for
      rigid spins, usually protons. The paper gives examples of MRI application of in
      vitro imaging of pharmaceutical dosage based on hydroxypropyl methylcellulose
      which have focused on water-penetration, diffusion, polymer swelling, and drug
      release, characterized with respect to other physical parameters such as pH and
      the molecular weight of polymer. Tetracycline hydrochloride was used as a model
      drug. NMR imaging of density distributions and fast kinetics of the dissolution
      behavior of compact tablets is presented for paracetamol tablets.

PMID- 21195170
TI  - Nanos1 functions as a translational repressor in the Xenopus germline.
AB  - Nanos family members have been shown to act as translational repressors in the
      Drosophila and Caenorhabditis elegans germline, but direct evidence is missing
      for a similar function in vertebrates. Using a tethered function assay, we show
      that Xenopus Nanos1 is a translational repressor and that association with the
      RNA is required for this repression. We identified a 14 amino acid region within
      the N-terminal domain of Nanos1 that is conserved in organisms as diverse as
      sponge and Human. The region is found in all vertebrates but notably lacking in
      Drosophila and C. elegans. Deletion and substitution analysis revealed that this
      conserved region was required for Nanos1 repressive activity. Consistent with
      this observation, deletion of this region was sufficient to prevent abnormal
      development that results from ectopic expression of Nanos1 in oocytes. Although
      Nanos1 can repress capped and polyadenylated RNAs, Nanos1 mediated repression did
      not require the targeted RNA to have a cap or to be polyadenylated. These results
      suggest that Nanos1 is capable of repressing translation by several different
      mechanisms. We found that Nanos1, like Drosophila Nanos, associates with cyclin
      B1 RNA in vivo indicating that some Nanos targets may be evolutionarily
      conserved. Nanos1 protein was detected and thus available to repress mRNAs while
      PGCs were in the endoderm, but was not observed in PGCs after this stage.

PMID- 21195172
TI  - From alternative methods to a new toxicology.
AB  - Mechanistic toxicology has evolved by relying, to a large extent, on
      methodologies that substitute or complement traditional animal tests. The
      biotechnology and informatics revolutions of the last decades have made such
      technologies broadly available and useful, but regulatory toxicology has been
      slow to embrace these new approaches. Major validation efforts, however, have
      delivered the evidence that new approaches do not lower safety standards and can
      be integrated into regulatory safety assessments. Particularly in the EU,
      political pressures, such as the REACH legislation and the 7th Amendment to the
      cosmetic legislation, have prompted the need of new approaches. In the US, the
      NRC vision report calling for a toxicology for the 21st century (and its most
      recent adaptation by EPA for their toxicity testing strategy) have initiated a
      debate about how to create a novel approach based on human cell cultures, lower
      species, high-throughput testing, and modeling. Lessons learned from the
      development, validation, and acceptance of alternative methods support the
      creation of a new approach based on identified toxicity pathways. Conceptual
      steering and an objective assessment of current practices by evidence-based
      toxicology (EBT) are required. EBT is modeled on evidence-based medicine, which
      has demonstrated that rigorous systematic reviews of current practices and meta
      analyses of studies provide powerful tools to provide health care professionals
      and patients with the current best scientific evidence. Similarly, a portal for
      high-quality reviews of toxicological approaches and tools for the quantitative
      meta-analyses of data promise to serve as door opener for a new regulatory
      toxicology.

PMID- 21195173
TI  - Calu-3 cells grown under AIC and LCC conditions: implications for dipeptide
      uptake and transepithelial transport of substances.
AB  - The aim of the present study was to investigate whether Calu-3 cell culture
      conditions influence drug and nutrient transport known to occur via carriers or
      transporters. Calu-3 cell layers, an in vitro model of the lung epithelium, were
      cultured using air interfaced culture (AIC) or liquid covered culture (LCC) on
      either polycarbonate or polyester as filter support material. We found that the
      development of the Calu-3 cell layer barrier function did not depend on the
      filter material but rather on the culture conditions as follows: (i) the apical
      uptake of Gly-Sar was significantly larger for cells grown in AIC compared to
      LCC, (ii) the TEER values for cells grown in LCC were approximately three times
      larger than for cells grown in AIC, (iii) the transepithelial transport in both
      AIC and LCC Calu-3 cells was polarized in the apical-basolateral direction of
      proline, glycine, alpha-methyl-d-glucoside, glipizide, taurocholic acid and
      estrone-3-sulfate, whereas inulin, mannitol and Gly-Sar showed no polarized
      transport. Etoposide showed polarized efflux (basolateral to apical transport) in
      AIC and LCC Calu-3 layers. These findings provide information about nutrient and
      drug transport in Calu-3 cells, and this may have implications for selecting
      culture conditions for transport studies in this in vitro model of the lung
      epithelium.

PMID- 21195174
TI  - Layer-by-layer assembly of poly(L-glutamic acid)/chitosan microcapsules for high
      loading and sustained release of 5-fluorouracil.
AB  - Hollow polyelectrolyte microcapsules based on poly(l-glutamic acid) (PLGA) and
      chitosan (CS) with opposite charges were fabricated by layer-by-layer (LbL)
      assembly technique using melamine formaldehyde (MF) microparticles as sacrificial
      templates. The LbL assembly of polyelectrolytes and the resultant PLGA/CS
      microcapsules were characterized. A hydrophilic anticancer drug, 5-fluorouracil
      (5-FU), was chosen to investigate the loading and release properties of the
      microcapsules. The PLGA/CS microcapsules show high loading capacity of 5-FU under
      conditions of high drug concentration and salt adding. The high loading can be
      ascribed to spontaneous deposition of 5-FU induced by hydrogen bonding between 5
      FU and PLGA/CS microcapsules. The PLGA/CS microcapsules show sustained release
      behavior. The release rate of 5-FU drastically slows down after loading in
      PLGA/CS microcapsules. The 5-FU release from PLGA/CS microcapsules can be best
      described using Ritger-Peppas or Baker-Londale models, indicating the diffusion
      mechanism of 5-FU release from the PLGA/CS microcapsules. In vitro cytotoxicity
      evaluation by the MTT assay shows good cell viability over the entire
      concentration range of PLGA/CS microcapsules. Therefore, the novel PLGA/CS
      microcapsules are expected to find application in drug delivery systems because
      of the properties of biodegradability, high loading, sustained release and cell
      compatibility.

PMID- 21195175
TI  - Comparison of ibuprofen release from minitablets and capsules containing
      ibuprofen: beta-cyclodextrin complex.
AB  - Mixtures containing ibuprofen (IB) complexed with beta-cyclodextrin (betaCD)
      obtained by two complexation methods [suspension/solution (with water removed by
      air stream, spray- and freeze-drying) and kneading technique] were processed into
      pharmaceutical dosage forms (minitablets and capsules). Powders (IB, betaCD and
      IBbetaCD) were characterized for moisture content, densities (true and bulk),
      angle of repose and Carr's index, X-ray and NMR. From physical mixtures and
      IBbetaCD complexes without other excipients were prepared 2.5-mm-diameter
      minitablets and capsules. Minitablets were characterized for the energy of
      compaction, tensile strength, friability, density and IB release (at pH 1.0 and
      7.2), whereby capsules were characterized for IB release. The results from the
      release of IB were analyzed using different parameters, namely, the similarity
      factor (f(2)), the dissolution efficiency (DE) and the amounts released at a
      certain time (30, 60 and 180 min) and compared statistically (alpha=0.05). The
      release of IB from the minitablets showed no dependency on the amount of water
      used in the formation of the complexes. Differences were due to the compaction
      force used or the presence of a shell for the capsules. The differences observed
      were mostly due to the characteristics of the particles (dependent on the method
      considered on the formation of the complexes) and neither to the dosage form nor
      to the complex of the IB.

PMID- 21195176
TI  - Identification and partial characterization of Rhizopus nigricans Gbeta proteins
      and their expression in the presence of progesterone.
AB  - The mammalian steroid hormone progesterone actuates a signalling pathway in the
      zygomycete Rhizopus nigricans which includes heterotrimeric G proteins. To
      investigate the possibility that the Gbeta subunit of these proteins is involved
      in the signalling, a cDNA library from R. nigricans exposed to progesterone was
      prepared and a sequence coding for a Gbeta subunit was searched for. Using
      degenerate primers, two sequences, RnGPB1 and RnGPB2, were identified that
      exhibited a high degree of identity with those for Gbeta from other filamentous
      fungi, but not from yeast. The presence of more than one Gbeta subunit is very
      rare among the fungi, and it has been to date reported only for Rhizopus oryzae.
      We have shown that progesterone increases the expression of RnGPB1, but has no
      influence on the expression of RnGPB2. Therefore, our studies imply the
      involvement of Gbeta subunit 1 in the response of R. nigricans to progesterone.
      Moreover, the Gbeta subunit is subjected to endogenous ADP-ribosylation in the
      presence of NAD, which could be important in some, as yet unknown, cell process.
      Article from a special issue on steroids and microorganisms.

PMID- 21195177
TI  - The role of the Aedes aegypti Epsilon glutathione transferases in conferring
      resistance to DDT and pyrethroid insecticides.
AB  - The Epsilon glutathione transferase (GST) class in the dengue vector Aedes
      aegypti consists of eight sequentially arranged genes spanning 53,645 bp on super
      contig 1.291, which maps to chromosome 2. One Epsilon GST, GSTE2, has previously
      been implicated in conferring resistance to DDT. The amino acid sequence of GSTE2
      in an insecticide susceptible and a DDT resistant strain differs at five residues
      two of which occur in the putative DDT binding site. Characterization of the
      respective recombinant enzymes revealed that both variants have comparable DDT
      dehydrochlorinase activity although the isoform from the resistant strain has
      higher affinity for the insecticide. GSTe2 and two additional Epsilon GST genes,
      GSTe5 and GSTe7, are expressed at elevated levels in the resistant population and
      the recombinant homodimer GSTE5-5 also exhibits low levels of DDT
      dehydrochlorinase activity. Partial silencing of either GSTe7 or GSTe2 by RNA
      interference resulted in an increased susceptibility to the pyrethroid,
      deltamethrin suggesting that these GST enzymes may also play a role in resistance
      to pyrethroid insecticides.

PMID- 21195178
TI  - Final steps in juvenile hormone biosynthesis in the desert locust, Schistocerca
      gregaria.
AB  - Two genes coding for enzymes previously reported to be involved in the final
      steps of juvenile hormone (JH) biosynthesis in different insect species, were
      characterised in the desert locust, Schistocerca gregaria. Juvenile hormone acid
      O-methyltransferase (JHAMT) was previously described to catalyse the conversion
      of farnesoic acid (FA) and JH acid to their methyl esters, methyl farnesoate (MF)
      and JH respectively. A second gene, CYP15A1 was reported to encode a cytochrome
      P450 enzyme responsible for the epoxidation of MF to JH. Additionally, a third
      gene, FAMeT (originally reported to encode a farnesoic acid methyltransferase)
      was included in this study. Using q-RT-PCR, all three genes (JHAMT, CYP15A1 and
      FAMeT) were found to be primarily expressed in the CA of the desert locust, the
      main biosynthetic tissue of JH. An RNA interference approach was used to verify
      the orthologous function of these genes in S. gregaria. Knockdown of the three
      genes in adult animals followed by the radiochemical assay (RCA) for JH
      biosynthesis and release showed that SgJHAMT and SgCYP15A1 are responsible for
      synthesis of MF and JH respectively. Our experiments did not show any involvement
      of SgFAMeT in JH biosynthesis in the desert locust. Effective and selective
      inhibitors of SgJHAMT and SgCYP15A1 would likely represent selective biorational
      locust control agents.

PMID- 21195179
TI  - Characterization of a new endogenous endo-beta-1,4-glucanase of Formosan
      subterranean termite (Coptotermes formosanus).
AB  - The present work characterized a new endogenous cellulase (endo-beta-1,4
      glucanase) gene, CfEG5, uncovered in the transcriptome of Formosan subterranean
      termite (Coptotermes formosanus). The full-length gene was cloned and sequenced.
      It is similar to the CfEG3a described earlier (Zhang et al., 2009) but not likely
      an allelic variant. GenomeWalkerTM DNA walking analysis indicated that there may
      be one copy of CfEG5 and two copies of CfEG3a in the termite genome. As with
      CfEG3a, the transcript of CfEG5 was detected predominantly in the salivary gland
      based on quantitative RT-PCR. Phylogenetic analysis of translated amino acid
      sequence showed that the CfEG5 is more related to CaEG, derived from an
      Australian subterranean termite (Coptotermes acinaciformis), than CfEG3a and
      other cellulases from Coptotermes formosanus, Reticulitermes speratus, or
      Reticulitermes flavipes. Recombinant CfEG5, produced in Escherichia coli, was
      active against filter-paper cellulose, resulting in mostly cellobiose and
      cellotriose, similar to the enzymatic and biochemical properties of CfEG3a. These
      findings would lead to further investigation of both the evolutionary origin of
      eukaryotic cellulase genes and the evolutionary relationship of termite species.
      The cellulose-degrading enzyme is applicable for bioconversion of wood to simple
      sugars and production of biofuels. The recombinant cellulase should also be
      useful for designing and screening of inhibitors for the development of target
      specific and environment-friendly bio-termicides.

PMID- 21195180
TI  - NGF and heart: Is there a role in heart disease?
AB  - The review emphasizes the role of NGF, the most representative member of the
      neurotrophins family, in cardiac physiopathology with a particular focus on
      healing and sprouting processes occurring after tissue damage. Cardiac and
      circulating NGF levels dramatically increase following myocardial injury (MI). A
      very early rise of this neurotrophin is indeed observed soon after MI (hours).
      Such a rise may lead to sympathetic nerve sprouting which may underlie the later
      genesis of arrhythmias but may also favor the healing process. At later times
      (months after), when heart failure develops, the opposite is detected and NGF
      tissue levels are below the normal range, an event that may in turn participate
      to defective innervation and cardiac failure. Through a careful analysis of
      preclinical and clinical studies, this review proposes that time is the key
      variable when studying these opposite changes in NGF expression observed
      following MI and attempting to interpret and correlate them with cardiac
      physiopathology. The examination of the results leads to the speculation that NGF
      modulation may be a pharmacological target for interventions in specific stages
      of heart dysfunction following MI.

PMID- 21195181
TI  - Serine recombinases as tools for genome engineering.
AB  - The serine recombinases differ mechanistically from the tyrosine recombinases and
      include proteins such as phiC31 integrase which, unlike Cre and Flp, promote
      unidirectional reactions. The serine recombinase family is large and includes
      many other proteins besides phiC31 integrase with the potential to be widely used
      in genome engineering. Here we review the details of the mechanism of the
      reactions promoted by the serine recombinases and discuss how these not only
      limit the utility of this class of recombinase but also creates opportunities for
      the engineering of new enzymes. We discuss the unanswered questions posed by
      genome engineering experiments in a variety of systems in which the serine
      recombinases have been used and finally describe more recently discovered serine
      recombinases that have the potential to be used in genome engineering.

PMID- 21195182
TI  - Analyzing the aggregation of polyglutamine-expansion proteins and its modulation
      by molecular chaperones.
AB  - Polyglutamine (polyQ)-expansion proteins cause protein aggregation in the cytosol
      and nucleus of neuronal cells, leading to neurodegenerative diseases. For
      example, expansion of the polyQ tract (>40 repeats) in huntingtin (htt) proteins
      leads to Huntington disease, while polyQ-expanded ataxins cause several types of
      ataxias. PolyQ-rich inclusions are found in neuronal cells of patients,
      suggesting that polyQ disease is caused by protein misfolding. However, the
      mechanisms by which polyQ-expansion proteins exert neuronal toxicity are largely
      unknown. Here, we review experimental procedures to analyze the roles of
      molecular chaperones in preventing polyQ aggregation and toxicity as well as to
      measure the characteristics and dynamics of polyQ aggregation, particularly
      focusing on cellular models and dynamic imaging of fluorescently-labeled polyQ
      expansion proteins and their modulation by chaperones.

PMID- 21195183
TI  - Approaches for probing the sequence space of substrates recognized by molecular
      chaperones.
AB  - Neurodegeneration, the progressive loss of function in neurons that eventually
      leads to their death, is the cause of many neurodegenerative disorders including
      Alzheimer's, Parkinson's, and Huntington's diseases. Protein aggregation is a
      hallmark of most neurodegenerative diseases, where unfolded proteins form
      intranuclear, cytosolic, and extracellular insoluble aggregates in neurons.
      Mounting evidence from studies in neurodegenerative disease models shows that
      molecular chaperones, key regulators of protein aggregation and degradation, play
      critical roles in the progression of neurodegeneration. Although chaperones
      exhibit promiscuity in their substrate specificity, specific molecular features
      are required for substrate recognition. Understanding the basis for substrate
      recognition by chaperones will aid in the development of therapeutic strategies
      that regulate chaperone expression levels in order to combat neurodegeneration.
      Many experimental techniques, including alanine scanning mutagenesis and phage
      display library screening, have been developed and applied to understand the
      basis of substrate recognition by chaperones. Here, we present computational
      algorithms that can be applied to rapidly screen the sequence space of potential
      substrates to determine the sequence and structural requirements for substrate
      recognition by chaperones.

PMID- 21195184
TI  - Refolding single-chain antibody (scFv) using lauroyl-L-glutamate as a
      solubilization detergent and arginine as a refolding additive.
AB  - Therapeutic potential of immunoconjugates has opened a new window for antibody
      based biopharmaceuticals. Greater tissue penetration and hence enhanced cell
      toxicity are obtained with a smaller version of antibodies. While the whole
      antibody can be readily produced via mammalian expression system, antibody
      fragments often require refolding of insoluble proteins. Here we report a new
      refolding method for antibody fragments using a novel amino acid-based detergent
      as a solubilizing agent and arginine-assisted refolding. Inclusion bodies of
      antibody fragments were solubilized by 2.5% lauroyl-L-Glu (C12-L-Glu) and
      successfully refolded by multi-step dilution into a buffer solution containing
      arginine hydrochloride and thiol/disulfide-exchange reagents. Adjustment of
      temperature was found to be critical for increase in the refolding yield.
      Although each protein requires appropriate optimization, solubilization by C12-L
      Glu and dilution refolding assisted by arginine can generate the native,
      functional antibody fragments. The procedure should enable us to utilize
      bacterial expression systems for the large-scale manufacturing.

PMID- 21195185
TI  - Dimer structure and conformational variability in the N-terminal region of an
      archaeal small heat shock protein, StHsp14.0.
AB  - Small heat shock proteins (sHsps), which are categorized into a class of
      molecular chaperones, bind and stabilize denatured proteins to prevent
      aggregation. The sHsps undergo transition between different oligomeric states to
      control their hydrophobicity. So far, only the structures of sHsps in large
      oligomeric states have been reported. Here we report the structure of StHsp14.0
      from Sulfolobus tokodaii in the dimeric state, which is formed by means of a
      mutation at the C-terminal IXI/V motif. The dimer is the sole building block in
      two crystal forms, and the dimeric mode is the same as that in the large
      oligomers. The N-terminal helix has variety in its conformation. Furthermore,
      spectroscopic and biochemical experiments were performed to investigate the
      conformational variability at the N-terminus. The structural, dynamical and
      oligomeric properties suggest that chaperone activity of StHsp14.0 is mediated by
      partially dissolved oligomers.

PMID- 21195186
TI  - The expression of two novel orange-spotted grouper (Epinephelus coioides) TNF
      genes in peripheral blood leukocytes, various organs, and fish larvae.
AB  - The tumour necrosis factor (TNF) super-family is a group of important cytokines
      involved in inflammation, apoptosis, cell proliferation, and the general
      stimulation of the immune system. The TNF gene has been cloned in some bony fish;
      however, its counterparts are still unidentified in the majority of fish species.
      In this study, we cloned gTNF-1 and gTNF-2 from the orange-spotted grouper
      (Epinephelus coioides), an economically important farmed fish. Both genes include
      4 exons and 3 introns and encoded 253 and 241 amino acid proteins with a
      molecular weight of approximately 27 and 26 kDa, respectively. The identity of
      the putative amino acid sequences between gTNF-1 and gTNF-2 was only 38%. The
      positions of cysteine residues, a protease cleavage site, and a transmembrane
      domain sequence derived from gTNF-1 and gTNF-2 were similar to those in other
      fish and mammalian TNF-alpha. The mRNA expression levels of the 2 gTNF molecules
      were evaluated in unstimulated/stimulated peripheral blood leukocytes, various
      organs, and fish larvae. Following lipopolysaccharide (LPS) treatment, gTNF-2 was
      expressed at higher levels, was up-regulated more quickly, and was more sensitive
      to the immune response than gTNF-1. gTNF-1 was constitutively expressed in the
      thymus, brain, and spleen, but it was also expressed in the heart, head kidney,
      and trunk kidney after LPS stimulation. gTNF-2 was constitutively expressed in
      the thymus, head kidney, trunk kidney, spleen, and intestine; further, gTNF-2 was
      highly expressed in all organs post-LPS stimulation. Finally, the gTNF expression
      levels were evaluated at various developmental stages in grouper larvae. A higher
      variation of gTNF expression levels was observed in fish larvae from a
      contaminated hatchery. This study revealed the different expression patterns of
      gTNF-1 and gTNF-2. In addition, gTNF-2 was more sensitive to pathogens than gTNF
      1; therefore, it may be an appropriate marker for pathogen invasion and the
      evaluation of the larval rearing environment.

PMID- 21195187
TI  - Working memory load modulates the auditory "What" and "Where" neural networks.
AB  - Working memory for sound identity (What) and sound location (Where) has been
      associated with increased neural activity in ventral and dorsal brain regions,
      respectively. To further ascertain this domain specificity, we measured fMRI
      signals during an n-back (n=1, 2) working memory task for sound identity or
      location, where stimuli selected randomly from three semantic categories (human,
      animal, and music) were presented at three possible virtual locations. Accuracy
      and reaction times were comparable in both "What" and "Where" tasks, albeit worse
      for the 2-back than for the 1-back condition. The analysis of fMRI data revealed
      greater activity in ventral and dorsal brain regions during sound identity and
      sound location, respectively. More importantly, there was an interaction between
      task and working memory load in the inferior parietal lobule (IPL). Within the
      right IPL, there were two sub-regions modulated differentially by working memory
      load: an anterior ventromedial region modulated by location load and a posterior
      dorsolateral region modulated by category load. These specific changes in neural
      activity as a function of working memory load reveal domain-specificity within
      the parietal cortex.

PMID- 21195188
TI  - EEG oscillatory patterns are associated with error prediction during music
      performance and are altered in musician's dystonia.
AB  - Skilled performance requires the ability to monitor ongoing behavior, detect
      errors in advance and modify the performance accordingly. The acquisition of fast
      predictive mechanisms might be possible due to the extensive training
      characterizing expertise performance. Recent EEG studies on piano performance
      reported a negative event-related potential (ERP) triggered in the ACC 70 ms
      before performance errors (pitch errors due to incorrect keypress). This ERP
      component, termed pre-error related negativity (pre-ERN), was assumed to reflect
      processes of error detection in advance. However, some questions remained to be
      addressed: (i) Does the electrophysiological marker prior to errors reflect an
      error signal itself or is it related instead to the implementation of control
      mechanisms? (ii) Does the posterior frontomedial cortex (pFMC, including ACC)
      interact with other brain regions to implement control adjustments following
      motor prediction of an upcoming error? (iii) Can we gain insight into the
      electrophysiological correlates of error prediction and control by assessing the
      local neuronal synchronization and phase interaction among neuronal populations?
      (iv) Finally, are error detection and control mechanisms defective in pianists
      with musician's dystonia (MD), a focal task-specific dystonia resulting from
      dysfunction of the basal ganglia-thalamic-frontal circuits? Consequently, we
      investigated the EEG oscillatory and phase synchronization correlates of error
      detection and control during piano performances in healthy pianists and in a
      group of pianists with MD. In healthy pianists, the main outcomes were increased
      pre-error theta and beta band oscillations over the pFMC and 13-15 Hz phase
      synchronization, between the pFMC and the right lateral prefrontal cortex, which
      predicted corrective mechanisms. In MD patients, the pattern of phase
      synchronization appeared in a different frequency band (6-8 Hz) and correlated
      with the severity of the disorder. The present findings shed new light on the
      neural mechanisms, which might implement motor prediction by means of forward
      control processes, as they function in healthy pianists and in their altered form
      in patients with MD.

PMID- 21195189
TI  - Reduced recruitment of orbitofrontal cortex to human social chemosensory cues in
      social anxiety.
AB  - Social anxiety refers to the prevalent and debilitating experience of fear and
      anxiety of being scrutinized in social situations. It originates from both
      learned (e.g. adverse social conditioning) and innate (e.g. shyness) factors.
      Research on social anxiety has traditionally focused on negative emotions induced
      by visual and auditory social cues in socially anxious clinical populations, and
      posits a dysfunctional orbitofrontal-amygdala circuit as a primary etiological
      mechanism. Yet as a trait, social anxiety is independent of one's specific
      emotional state. Here we probe the neural substrate of intrinsic social anxiety
      by employing a unique type of social stimuli, airborne human social chemosensory
      cues that are inherently social, ubiquitously present, and yet operating below
      verbal awareness. We show that the adopted social chemosensory cues were not
      perceived to be human-related, did not differentially bias self-report of anxiety
      or autonomic nervous system responses, yet individuals with elevated social
      anxiety demonstrated a reduced recruitment of the orbitofrontal cortex to social
      chemosensory cues. No reciprocal activity in the amygdala was observed. Our
      findings point to an intrinsic neural substrate underlying social anxiety that is
      not associated with prior adverse social conditioning, thereby providing the
      first neural evidence for the inherent social aspect of this enigmatic
      phenomenon.

PMID- 21195190
TI  - Reduced visual processing capacity in sleep deprived persons.
AB  - Multiple experiments have found sleep deprivation to lower task-related parietal
      and extrastriate visual activation, suggesting a reduction of visual processing
      capacity in this state. The perceptual load theory of attention (Lavie, 1995)
      predicts that our capacity to process unattended distractors will be reduced by
      increasing perceptual difficulty of task-relevant stimuli. Here, we evaluated the
      effects of sleep deprivation and perceptual load on visual processing capacity by
      measuring neural repetition-suppression to unattended scenes while healthy
      volunteers attended to faces embedded in face-scene pictures. Perceptual load did
      not affect repetition suppression after a normal night of sleep. Sleep
      deprivation reduced repetition suppression in the parahippocampal place area
      (PPA) in the high but not low perceptual load condition. Additionally, the extent
      to which task-related fusiform face area (FFA) activation was reduced after sleep
      deprivation correlated with behavioral performance and lowered repetition
      suppression in the PPA. The findings concerning correct responses indicate that a
      portion of stimulus related activation following a normal night of sleep
      contributes to potentially useful visual processing capacity that is attenuated
      following sleep deprivation. Finally, when unattended stimuli are not highly
      intrusive, sleep deprivation does not appear to increase distractibility.

PMID- 21195192
TI  - Neural correlates of reality monitoring during adolescence.
AB  - BACKGROUND: Reality monitoring processes serve the critical function of
      discriminating between externally derived information and self-generated
      information. Several reality monitoring studies with healthy adult participants
      have identified the anterior prefrontal cortex (PFC) as consistently engaged
      during the recollection of self-generated contextual cues. Furthermore, reduced
      activity of medial PFC has been linked with schizotypal trait expression of
      delusion and hallucination-like symptoms in healthy adults undergoing fMRI
      reality-monitoring tasks. The present study seeks to examine the cerebral
      underpinnings of reality monitoring during adolescence, a developmental stage
      where the expression of schizotypal traits may increase risk for psychosis.
      METHOD: A group of 33 adolescents, assessed using the Schizotypal Personality
      Scale (SPQ), underwent fMRI while performing a reality monitoring task. After an
      encoding session where the subject or the experimenter read out a series of
      complete or incomplete word pairs, subjects were presented with the first word of
      studied word pairs and asked whether the corresponding word had been: (1)
      perceived or produced (context monitoring), or (2) read by the subject or by the
      experimenter (origin monitoring). RESULTS: Analyses revealed a common set of
      activated brain areas during both context and origin monitoring conditions. When
      compared to context monitoring, origin monitoring was associated with greater
      activation in anterior PFC within Brodmann area 10 (BA 10). Correlation analyses
      revealed that reduced signal change in BA 10 during origin monitoring was
      associated with greater schizotypal trait expression. CONCLUSION: Much like
      adults performing a similar reality monitoring task, adolescents exhibit a common
      pattern of brain activity during origin and context monitoring, with functional
      specialization within the prefrontal cortex involving preferential activation of
      BA 10 during origin monitoring. Greater schizotypal trait expression appears to
      be significantly associated to reduced BA 10 activity during origin monitoring
      trials. Results are discussed in relation to cortical specialization within the
      PFC and trait expression during adolescence.

PMID- 21195191
TI  - fMRI investigation of unexpected somatosensory feedback perturbation during
      speech.
AB  - Somatosensory feedback plays a critical role in the coordination of articulator
      movements for speech production. In response to unexpected resistance to lip or
      jaw movements during speech, fluent speakers can use the difference between the
      somatosensory expectations of a speech sound and the actual somatosensory
      feedback to adjust the trajectories of functionally relevant but unimpeded
      articulators. In an effort to investigate the neural substrates underlying the
      somatosensory feedback control of speech, we used an event-related sparse
      sampling functional magnetic resonance imaging paradigm and a novel pneumatic
      device that unpredictably blocked subjects' jaw movements. In comparison to
      speech, perturbed speech, in which jaw perturbation prompted the generation of
      compensatory speech motor commands, demonstrated increased effects in bilateral
      ventral motor cortex, right-lateralized anterior supramarginal gyrus, inferior
      frontal gyrus pars triangularis and ventral premotor cortex, and bilateral
      inferior posterior cerebellum (lobule VIII). Structural equation modeling
      revealed a significant increased influence from left anterior supramarginal gyrus
      to right anterior supramarginal gyrus and from left anterior supramarginal gyrus
      to right ventral premotor cortex as well as a significant increased reciprocal
      influence between right ventral premotor cortex and right ventral motor cortex
      and right anterior supramarginal gyrus and right inferior frontal gyrus pars
      triangularis for perturbed speech relative to speech. These results suggest that
      bilateral anterior supramarginal gyrus, right inferior frontal gyrus pars
      triangularis, right ventral premotor and motor cortices are functionally coupled
      and influence speech motor output when somatosensory feedback is unexpectedly
      perturbed during speech production.

PMID- 21195193
TI  - Global-two-stage filtering of clinical PET parametric maps: application to
      [(11)C]-(R)-PK11195.
AB  - INTRODUCTION: In Positron Emission Tomography (PET) quantification of
      physiological parameters at the voxel level may result in unreliable estimates
      due to the high noise of voxel time activity curves. Global-Two-Stage (GTS), an
      estimation technique belonging to the group of "population approaches", can be
      used to tackle this problem. GTS was previously tested on simulated PET data and
      yielded substantial improvements when compared to standard estimation approaches
      such as Weighted NonLinear Least Squares (WNLLS) and Basis Function Method (BFM).
      In this work GTS performance is assessed in a clinical context using the
      neuroinflammation marker [(11)C]-(R)-PK11195 applied to a cohort of Huntington's
      disease (HD) patients with and without symptoms. MATERIALS AND METHODS:
      Parametric maps of binding potential (BP(ND)) of 12 normal controls (NC), 9
      symptomatic and 9 presymptomatic HD patients were generated by applying a
      modified reference tissue model that accounts for tracer vascular activity in
      both reference and target tissues (SRTMV). GTS was then applied to SRTMV maps and
      its performance compared with that of SRTMV. Three smoothed versions of SRTMV,
      obtained by filtering the original SRTMV maps with Gaussian filters of 3 mm, 5 mm
      and 7 mm Full Width Half Maximum (FWHM), were also included in the comparison.
      Since striatal degeneration is the hallmark of HD, sensitivity was assessed for
      all methods by computing the mean of z-scores in caudate, putamen and globus
      pallidus in the voxel-by-voxel statistical comparison of BP(ND) between HD and
      NC. RESULTS: Application of GTS to parametric maps brought a substantial
      qualitative improvement to SRTMV maps to the extent that anatomical structures
      often became visible. In addition, most parameter estimates that were outside the
      physiological range with SRTMV were corrected by GTS. GTS yielded a 2.3-fold
      increase in sensitivity with respect to SRTMV for the symptomatic cohort (mean of
      striatal z-scores of 0.76 for SRTMV and 1.79 for GTS) and an even more
      substantial increase for the presymptomatic cohort (mean of striatal z-scores of
      0.34 for SRTMV and 0.96 for GTS). The sensitivity of GTS was similar to the one
      obtained with a filter of 7 mm FWHM applied to the initial SRTMV maps but GTS
      images were not characterized by the notable loss of resolution typical of
      smoothed maps. GTS, additionally, does not require to change/define settings
      according to the tracer and level of noise, whereas the choice of the FWHM value
      of the Gaussian filter normally employed in the smoothing procedure is typically
      arbitrary. CONCLUSIONS: GTS is a powerful and robust tool for improving the
      quality of parametric maps in PET. The method is particularly appealing in that
      it can be applied to any tracer and estimation method, provided that initial
      estimates of the parameter vector and of its covariance are available. Although
      the benefits of GTS are far from being exhaustively assessed, the significant
      improvements obtained both on real and simulated data suggest that it could
      become an important tool for dynamic PET in the future.

PMID- 21195194
TI  - Common and distinct neural networks for false-belief reasoning and inhibitory
      control.
AB  - Ample behavioral evidence has shown that the ability to attribute false beliefs
      as part of a Theory of Mind (ToM) and the ability to inhibit a prepotent response
      are strongly correlated in both children and adults. Frequently reported areas
      associated with both processes are the right temporo-parietal junction (TPJ) and
      the medial prefrontal cortex (MPFC). Nevertheless, the exact nature of the
      relationship between belief-reasoning and inhibitory control at the neural level
      remains unclear. A functional magnetic resonance imaging (fMRI) study was
      conducted to investigate the neural correlates of belief-reasoning and inhibitory
      control in a within-subjects design using virtually identical visual stimuli. A
      false-belief task was used to investigate belief-attribution. The neural
      correlates of response inhibition were measured using a Go/No-Go task. Besides
      distinct activation for belief-reasoning and inhibitory control, the results also
      showed a substantial overlap for both processes in the right superior dorsal
      MPFC, the right TPJ, the dorsal part of the left TPJ, and lateral prefrontal
      areas. These findings suggest that the previously described behavioral link
      between belief attribution and inhibitory control may be explained by a common
      recruitment of brain areas related to domain-general cognitive processes. Also,
      the results indicate that neither the right TPJ nor MPFC is specific to the
      attribution of false beliefs.

PMID- 21195195
TI  - Subchronic duloxetine administration alters the extended amygdala circuitry in
      healthy individuals.
AB  - Neuroimaging studies have consistently linked depression to hyperactivation of a
      (para)limbic affective processing network centered around the amygdala. Recent
      studies have started to investigate how antidepressant drugs affect amygdala
      reactivity in healthy individuals, but the influence of their subchronic
      administration on the functional integrity of the affective neurocircuitry as a
      whole remains unknown. Therefore, we used functional magnetic resonance imaging
      in nineteen healthy volunteers to assess the effect of two weeks of
      administration of the combined serotonin and norepinephrine reuptake inhibitor
      duloxetine (60 mg) on reactivity and functional connectivity within the affective
      neurocircuitry in a double-blind, placebo-controlled, crossover design. Using an
      emotional face matching task we demonstrated that duloxetine reduced neural
      responses in affect processing regions including the amygdala, the anterior
      insula, the thalamus and the ventral aspect of the anterior cingulate cortex.
      Additionally, functional coupling between the amygdala and the anterior insula
      was enhanced by the drug. These results suggest that duloxetine attenuates the
      bottom-up processing of biologically salient information in an extended amygdala
      circuitry, while at the same time possibly potentiating the effective
      communication between its subparts. Since hyperactivation of the same affective
      neurocircuitry is thought to underlie emotional dysfunction in depression, these
      results suggest a putative neural mechanism through which duloxetine could
      normalize typical negativity biases in depression.

PMID- 21195196
TI  - BDNF gene effects on brain circuitry replicated in 455 twins.
AB  - Brain-derived neurotrophic factor (BDNF) plays a key role in learning and memory,
      but its effects on the fiber architecture of the living brain are unknown. We
      genotyped 455 healthy adult twins and their non-twin siblings (188 males/267
      females; age: 23.7+/-2.1 years, mean+/-SD) and scanned them with high angular
      resolution diffusion tensor imaging (DTI), to assess how the BDNF Val66Met
      polymorphism affects white matter microstructure. By applying genetic association
      analysis to every 3D point in the brain images, we found that the Val-BDNF
      genetic variant was associated with lower white matter integrity in the splenium
      of the corpus callosum, left optic radiation, inferior fronto-occipital
      fasciculus, and superior corona radiata. Normal BDNF variation influenced the
      association between subjects' performance intellectual ability (as measured by
      Object Assembly subtest) and fiber integrity (as measured by fractional
      anisotropy; FA) in the callosal splenium, and pons. BDNF gene may affect the
      intellectual performance by modulating the white matter development. This
      combination of genetic association analysis and large-scale diffusion imaging
      directly relates a specific gene to the fiber microstructure of the living brain
      and to human intelligence.

PMID- 21195197
TI  - Neuroanatomical spatial patterns in Turner syndrome.
AB  - Turner syndrome (TS) is a highly prevalent genetic condition caused by partial or
      complete absence of one X-chromosome in a female and is associated with a lack of
      endogenous estrogen during development secondary to gonadal dysgenesis. Prominent
      cognitive weaknesses in executive and visuospatial functions in the context of
      normal overall IQ also occur in affected individuals. Previous neuroimaging
      studies of TS point to a profile of neuroanatomical variation relative to age and
      sex matched controls. However, there are no neuroimaging studies focusing on
      young girls with TS before they receive exogenous estrogen treatment to induce
      puberty. Information obtained from young girls with TS may help to establish an
      early neural correlate of the cognitive phenotype associated with the disorder.
      Further, univariate analysis has predominantly been the method of choice in prior
      neuroimaging studies of TS. Univariate approaches examine between-group
      differences on the basis of individual image elements (i.e., a single voxel's
      intensity or the volume of an a priori defined brain region). This is in contrast
      to multivariate methods that can elucidate complex neuroanatomical profiles in a
      clinical population by determining the pattern of between-group differences from
      many image elements evaluated simultaneously. In this case, individual image
      elements might not be significantly different between groups but can still
      contribute to a significantly different overall spatial pattern. In this study,
      voxel-based morphometry (VBM) of high-resolution magnetic resonance images was
      used to investigate differences in brain morphology between 13 pediatric, pre
      estrogen girls with monosomic TS and 13 age-matched typically developing controls
      (3.0 T imaging: mean age 9.1+/-2.1). A similar analysis was performed with an
      older cohort of 13 girls with monosomic TS and 13 age-matched typically
      developing controls (1.5 T imaging: mean age 15.8+/-4.5). A multivariate, linear
      support vector machine analysis using leave-one-out cross-validation was then
      employed to discriminate girls with TS from typically developing controls based
      on differences in neuroanatomical spatial patterns and to assess how accurately
      such patterns translate across heterogeneous cohorts. VBM indicated that both TS
      cohorts had significantly reduced gray matter volume in the precentral,
      postcentral, and supramarginal gyri and enlargement of the left middle and
      superior temporal gyri. Support vector machine (SVM) classifiers achieved high
      accuracy for discriminating brain morphology patterns in TS from typically
      developing controls and also displayed spatial patterns consistent with the VBM
      results. Furthermore, the SVM classifiers identified additional neuroanatomical
      variations in individuals with TS, localized in the hippocampus, orbitofrontal
      cortex, insula, caudate, and cuneus. Our results demonstrate robust spatial
      patterns of altered brain morphology in developmentally dynamic populations with
      TS, providing further insight into the neuroanatomical correlates of cognitive
      behavioral features in this condition.

PMID- 21195198
TI  - Discrete neural substrates underlie complementary audiovisual speech integration
      processes.
AB  - The ability to combine information from multiple sensory modalities into a
      single, unified percept is a key element in an organism's ability to interact
      with the external world. This process of perceptual fusion, the binding of
      multiple sensory inputs into a perceptual gestalt, is highly dependent on the
      temporal synchrony of the sensory inputs. Using fMRI, we identified two
      anatomically distinct brain regions in the superior temporal cortex, one involved
      with processing temporal-synchrony, and one with processing perceptual fusion of
      audiovisual speech. This dissociation suggests that the superior temporal cortex
      should be considered a "neuronal hub" composed of multiple discrete subregions
      that underlie an array of complementary low- and high-level multisensory
      integration processes. In this role, abnormalities in the structure and function
      of superior temporal cortex provide a possible common etiology for temporal
      processing and perceptual-fusion deficits seen in a number of clinical
      populations, including individuals with autism spectrum disorder, dyslexia, and
      schizophrenia.

PMID- 21195199
TI  - Principles of recovery from traumatic brain injury: reorganization of functional
      networks.
AB  - Recovery after brain injury is an excellent platform to study the mechanism
      underlying brain plasticity, the reorganization of networks. Do complex network
      measures capture the physiological and cognitive alterations that occurred after
      a traumatic brain injury and its recovery? Patients as well as control subjects
      underwent resting-state MEG recording following injury and after
      neurorehabilitation. Next, network measures such as network strength, path
      length, efficiency, clustering and energetic cost were calculated. We show that
      these parameters restore, in many cases, to control ones after recovery,
      specifically in delta and alpha bands, and we design a model that gives some
      hints about how the functional networks modify their weights in the recovery
      process. Positive correlations between complex network measures and some of the
      general index of the WAIS-III test were found: changes in delta-based path-length
      and those in Performance IQ score, and alpha-based normalized global efficiency
      and Perceptual Organization Index. These results indicate that: 1) the principle
      of recovery depends on the spectral band, 2) the structure of the functional
      networks evolves in parallel to brain recovery with correlations with
      neuropsychological scales, and 3) energetic cost reveals an optimal principle of
      recovery.

PMID- 21195200
TI  - Phylogenetic relationships in the spoon tarsus subgroup of Hawaiian Drosophila:
      conflict and concordance between gene trees.
AB  - The Hawaiian Drosophilidae contains approximately 1000 species, placed in species
      groups and subgroups based largely on secondary sexual modifications to wings,
      forelegs and mouthparts. Members of the spoon tarsus subgroup possess a cup
      shaped structure on the foretarsi of males. Eight of the twelve species in this
      subgroup are found only on the Big Island of Hawaii, suggesting that they have
      diverged within the past 600,000 years. This rapid diversification has made
      determining the relationships within this group difficult to infer. We use 13
      genes, including nine rapidly evolving nuclear loci, to estimate relationships
      within the spoon tarsus species, as well as to test the monophyly of this
      subgroup. A variety of analytical approaches are used, including individual and
      concatenated analyses, Bayesian estimation of species trees and Bayesian
      untangling of concordance knots. We find widespread agreement between
      phylogenetic estimates derived from different methods, although some incongruence
      is present. Notably, our analyses suggest that the spoon tarsus subgroup, as
      currently defined, is not monophyletic.

PMID- 21195201
TI  - Molecular taxonomy and phylogenetic affinities of two groundwater amphipods,
      Crangonyx islandicus and Crymostygius thingvallensis, endemic to Iceland.
AB  - The amphipod superfamily Crangonyctoidea is distributed exclusively in freshwater
      habitats worldwide and is characteristic of subterranean habitats. Two members of
      the family, Crangonyx islandicus and Crymostygius thingvallensis, are endemic to
      Iceland and were recently discovered in groundwater underneath lava fields.
      Crangonyx islandicus belongs to a well-known genus with representatives both in
      North America and in Eurasia. Crymostygius thingvallensis defines a new family,
      Crymostygidae. Considering the incongruences observed recently between molecular
      and morphological taxonomy within subterranean species, we aim to assess the
      taxonomical status of the two species using molecular data. Additionally, the
      study contributes to the phylogenetic relationships among several
      crangonyctoidean species and specifically among species from four genera of the
      family Crangonyctidae. Given the available data we consider how the two Icelandic
      species could have colonized Iceland, by comparing geographical origin of the
      species with the phylogeny. Regions of two nuclear (18S and 28S rRNA) and two
      mitochondrial genes (16S rRNA and COI) for 20 different species of three families
      of the Crangonyctoidea were sequenced. Four different methods were used to align
      the RNA gene sequences and phylogenetic trees were constructed using bayesian and
      maximum likelihood analysis. The Crangonyctidae monophyly is supported. Crangonyx
      islandicus appeared more closely related to species from the Nearctic region.
      Crymostygius thingvallensis is clearly divergent from the other species of
      Crangonyctoidea. Crangonyx and Synurella genera are clearly polyphyletic and
      showed a geographical association, being split into a Nearctic and a Palearctic
      group. This research confirms that the studied species of Crangonyctidae share a
      common ancestor, which was probably widespread in the Northern hemisphere well
      before the break up of Laurasia. The Icelandic species are of particular interest
      since Iceland emerged after the separation of Eurasia and North America, is
      geographically isolated and has repeatedly been covered by glaciers during the
      Ice Age. The close relation between Crangonyx islandicus and North American
      species supports the hypothesis of the Trans-Atlantic land bridge between
      Greenland and Iceland which might have persisted until 6 million years ago. The
      status of the family Crymostygidae is supported, whereas Crangonyx islandicus
      might represent a new genus. As commonly observed in subterranean animals,
      molecular and morphological taxonomy led to different conclusions, probably due
      to convergent evolution of morphological traits. Our molecular analysis suggests
      that the family Crangonyctidae needs taxonomic revisions.

PMID- 21195203
TI  - Use of a continuous culture fermentation system to investigate the effect of
      GanedenBC30 (Bacillus coagulans GBI-30, 6086) supplementation on pathogen
      survival in the human gut microbiota.
AB  - Single-stage continuous fermentation systems were employed to examine the effects
      of GanedenBC(30) supplementation on the human gastrointestinal microbiota in
      relation to pathogen challenge in vitro. Denaturing gradient gel electrophoresis
      analysis demonstrated that GanedenBC(30) supplementation modified the microbial
      profiles in the fermentation systems compared with controls, with profiles
      clustering according to treatment. Overall, GanedenBC(30) supplementation did not
      elicit major changes in bacterial population counts in vitro, although notably
      higher Bcoa191 counts were seen following probiotic supplementation (compared to
      the controls). Pathogen challenge did not elicit significant modification of the
      microbial counts in vitro, although notably higher Clit135 counts were seen in
      the control system post-Clostridium difficile challenge than in the corresponding
      GanedenBC(30)-supplemented systems. Sporulation appears to be associated with the
      anti-microbial activity of GanedenBC(30), suggesting that a bi-modal lifecycle of
      GanedenBC(30)in vivo may lead to anti-microbial activity in distal regions of the
      gastrointestinal tract.

PMID- 21195202
TI  - Cognitive neuroepigenetics: a role for epigenetic mechanisms in learning and
      memory.
AB  - Although long-lasting behavioral memories have long been thought to require
      equally persistent molecular changes, little is known about the biochemical
      underpinnings of memory storage and maintenance. Increasing evidence now suggests
      that long-term behavioral change may be associated with epigenetic regulation of
      transcription in the central nervous system. In this review, we present evidence
      that changes in DNA methylation contribute to memory formation and maintenance,
      consider how DNA methylation affects readout of memory-related genes, and discuss
      how these changes may be important in the large-scale context of memory circuits.
      Finally, we discuss potential challenges involved in examining epigenetic changes
      in the brain and highlight how epigenetic mechanisms may be relevant for other
      cognitive processes.

PMID- 21195204
TI  - Functional analysis of a mitochondrial phosphopantetheinyl transferase (PPTase)
      gene pptB in Aspergillus fumigatus.
AB  - The mitochondrial phosphopantetheinyl transferase gene pptB of the opportunistic
      pathogen Aspergillus fumigatus has been identified and characterised. Unlike
      pptA, which is required for lysine biosynthesis, secondary metabolism, and iron
      assimilation, pptB is essential for viability. PptB is located in the
      mitochondria. In vitro expression of pptA and pptB has shown that PptB is
      specific for the mitochondrial acyl carrier protein AcpA.

PMID- 21195205
TI  - Regulatory mechanisms of nitric oxide and reactive oxygen species generation and
      their role in plant immunity.
AB  - Rapid production of nitric oxide (NO) and reactive oxygen species (ROS) has been
      implicated in diverse physiological processes, such as programmed cell death,
      development, cell elongation and hormonal signaling, in plants. Much attention
      has been paid to the regulation of plant innate immunity by these signal
      molecules. Recent studies provide evidence that an NADPH oxidase, respiratory
      burst oxidase homolog, is responsible for pathogen-responsive ROS burst. However,
      we still do not know about NO-producing enzymes, except for nitrate reductase,
      although many studies suggest the existence of NO synthase-like activity
      responsible for NO burst in plants. Here, we introduce regulatory mechanisms of
      NO and ROS bursts by mitogen-activated protein kinase cascades, calcium-dependent
      protein kinase or riboflavin and its derivatives, flavin mononucleotide and
      flavin adenine dinucleotide, and we discuss the roles of the bursts in defense
      responses against plant pathogens.

PMID- 21195206
TI  - Structural characterization of the polar lipids of Clostridium novyi NT. Further
      evidence for a novel anaerobic biosynthetic pathway to plasmalogens.
AB  - A study of the polar lipids of Clostridium novyi NT has revealed the presence of
      phosphatidylethanolamine (PE) and cardiolipin as major phospholipids with smaller
      amounts of phosphatidylglycerol (PG), lysyl-PG and alanyl-PG. Other minor
      phospholipids included phosphatidic acid, CDP-diacylglycerol, phosphatidylserine
      (PS) and phosphatidylthreonine (PT). PE, PG and amino acyl PG were present in
      both the diacyl and alk-1'-enyl acyl (plasmalogen) forms and cardiolipin
      plasmalogens were found to contain one or two alk-1'-enyl chains. In contrast,
      the precursor lipids phosphatidic acid, CDP-diacylglycerol and PS were present
      almost exclusively as diacyl phospholipids. These findings are consistent with
      the hypothesis that plasmalogens are formed from diacylated phospholipids at a
      late stage of phospholipid formation in Clostridium species. This novel pathway
      contrasts with the route in animals in which a saturated ether bond is formed at
      an early stage of plasmalogen biosynthesis and the alk-1-enyl bond is formed by
      an aerobic mechanism.

PMID- 21195207
TI  - Ontology modularization to improve semantic medical image annotation.
AB  - Searching for medical images and patient reports is a significant challenge in a
      clinical setting. The contents of such documents are often not described in
      sufficient detail thus making it difficult to utilize the inherent wealth of
      information contained within them. Semantic image annotation addresses this
      problem by describing the contents of images and reports using medical
      ontologies. Medical images and patient reports are then linked to each other
      through common annotations. Subsequently, search algorithms can more effectively
      find related sets of documents on the basis of these semantic descriptions. A
      prerequisite to realizing such a semantic search engine is that the data
      contained within should have been previously annotated with concepts from medical
      ontologies. One major challenge in this regard is the size and complexity of
      medical ontologies as annotation sources. Manual annotation is particularly time
      consuming labor intensive in a clinical environment. In this article we propose
      an approach to reducing the size of clinical ontologies for more efficient manual
      image and text annotation. More precisely, our goal is to identify smaller
      fragments of a large anatomy ontology that are relevant for annotating medical
      images from patients suffering from lymphoma. Our work is in the area of ontology
      modularization, which is a recent and active field of research. We describe our
      approach, methods and data set in detail and we discuss our results.

PMID- 21195208
TI  - Electrical dyssynchrony and resynchronization in tetralogy of Fallot.

PMID- 21195209
TI  - To the editor--Biological pacemakers exhibit positive chronotropic response to
      emotional arousal.

PMID- 21195210
TI  - Ventricular arrhythmia and sleep-related breathing disorders.

PMID- 21195211
TI  - Impact of circulating monocyte CD36 level on atrial fibrillation and subsequent
      catheter ablation.
AB  - BACKGROUND: Inflammation, an important mechanism in the pathogenesis of atrial
      fibrillation (AF), can be regulated by CD36 in monocytes. OBJECTIVE: The purpose
      of this study was to test the hypothesis that CD36 in monocytes contributes to
      the pathogenesis of AF. METHODS: A prospective study that enrolled 87 patients
      with AF and 70 without AF was conducted. RESULTS: Compared to patients without
      AF, patients with AF had monocytes with a lower level of CD36 protein, which
      correlated with left atrial diameter, left atrial emptying fraction, and left
      atrial mean voltage. In AF patients after catheter ablation, Kaplan-Meier
      analysis showed that the sinus rhythm maintenance rate was higher in patients
      with high CD36 levels. Low CD36 level was an independent predictor of recurrence.
      After successful ablation, the CD36 level increased by 57%, reaching that of
      control patients. CD36 level was not correlated with the level of high
      sensitivity C-reactive protein. Analysis of mRNA levels from a buffy coat
      revealed that AF patients had lower CD36 and interleukin-10 levels and higher
      peroxisome proliferator-activated receptor-gamma and tumor necrosis factor-alpha
      levels, with CD36 level positively correlated with interleukin-10 level but
      inversely correlated with peroxisome proliferator-activated receptor-gamma and
      tumor necrosis factor-alpha levels. CONCLUSION: Low CD36 levels in circulating
      monocytes were associated with AF occurrence and predicted recurrence after
      catheter ablation. The link between CD36 and AF identified a novel AF-related
      inflammatory pathway.

PMID- 21195212
TI  - Fetal nicotine exposure increases airway responsiveness and alters airway wall
      composition in young lambs.
AB  - To test the hypotheses that fetal nicotine exposure alters airway wall
      composition and enhances the airway response to inhaled methacholine (MCh), lambs
      were exposed during the last fetal trimester to (1) a low dose (LN) (n=13,
      0.5mg/kg/d (maternal weight) of free base nicotine, (2) a moderate dose (MN)
      (n=10, 1.5mg/kg/d) or (3) saline (n=14). Studies were performed at postnatal days
      12, 26 and 52. Prenatal nicotine exposure induced a dose- and age-related hyper
      responsiveness to MCh in the proximal airways. Moment analysis of nitrogen decay
      curves showed no nicotine or MCh effects on ventilation homogeneity or gas-mixing
      efficiency in the distal airways during MCh inhalations suggesting a bimodal
      response. Fetal nicotine exposure increased epithelial mucosubstance volume in
      central (LN, MN) and distal bronchi (LN), increased smooth muscle volume in
      distal bronchi and bronchioles (LN) and decreased bronchiolar diameter (MN). In
      conclusion, third trimester nicotine exposure causes hyperreactive proximal
      airways and alters proximal airway wall composition associated with airflow
      limitation.

PMID- 21195213
TI  - Lipopolysaccharide signaling in the carotid chemoreceptor pathway of rats with
      sepsis syndrome.
AB  - In addition to their role in cardiorespiratory regulation, carotid body (CB)
      chemoreceptors serve as sensors for inflammatory status and as a protective
      factor during sepsis. However, lipopolysaccharide-induced sepsis (LPS) reduces CB
      responsiveness to excitatory or depressant stimuli. We tested whether LPS exerts
      a direct effect on the carotid chemoreceptor pathway, the CB and its sensory
      ganglion. We determined that the rat CB and nodose-petrosal-jugular ganglion
      complex (NPJgc) express TLR4, TNF-alpha and its receptors (TNF-R1 and TNF-R2).
      LPS administration (15mg/kg intraperitoneally) evoked MyD88-mechanism pathway
      activation in CB and NPJgc, with NF-kappaB p65, p38 MAPK, and ERK activation.
      Consistently, LPS increased TNF-alpha and TNF-R2. Double-labeling studies showed
      that the aforementioned pathway occurs in TH-containing glomus cells and NPJgc
      neurons, components of the chemosensitive neural pathway. Thus, our results
      suggest that LPS acting directly through TLR4/MyD88-mechanism pathways increases
      TNF-alpha and TNF-R2 expression in the carotid chemoreceptor pathway. These
      results show a novel afferent pathway to the central nervous system during
      endotoxemia, and could be relevant in understanding sepsis pathophysiology and
      therapy.

PMID- 21195214
TI  - Anti-fouling bioactive surfaces.
AB  - Bioactive surfaces refer to surfaces with immobilized bioactive molecules aimed
      specifically at promoting or supporting particular interactions. Such surfaces
      are of great importance for various biomedical and biomaterials applications. In
      the past few years, considerable effort has been made to create bioactive
      surfaces by forming specific biomolecule-modified surfaces on a non-biofouling
      "base" or "background". Hydrophilic and bioinert polymers have been widely used
      as anti-fouling layers that resist non-specific protein interactions. They can
      also serve as "spacers" to effectively move the immobilized biomolecule away from
      the surface, thus enhancing its bioactivity. In this review we summarize several
      successful approaches for the design and preparation of bioactive surfaces based
      on different types of anti-fouling/spacer materials. Some perspectives on future
      research in this area are also presented.

PMID- 21195215
TI  - Do angiotensin converting enzyme inhibitors improve walking distance in patients
      with symptomatic lower limb arterial disease? A systematic review and meta
      analysis of randomised controlled trials.
AB  - BACKGROUND: Several studies have reported the clinical effects of long-term
      treatment with cardioprotective medications in patients with lower limb
      peripheral arterial disease (PAD) in terms of reducing cardiovascular morbidity
      and mortality. A number of these studies investigated the clinical effect of
      angiotensin converting enzyme inhibitors (ACEIs) on walking distance in this
      group of patients. OBJECTIVE: To review the evidence regarding the effects of
      ACEIs in patients with symptomatic PAD of the lower limbs in terms of the effect
      on maximum and pain-free walking distances and ankle brachial pressure index
      (ABPI). METHODS: A systematic literature search of the medical literature from
      1966 to 2010 on randomized placebo-controlled trials which assessed the effect of
      ACEIs on maximum and/or pain-free walking distances and/or ABPI in patients with
      symptomatic lower limbs PAD was performed. Data from included studies were pooled
      with use of random-effects model with standard mean differences. Heterogeneity
      across studies was assessed with calculation of I(2) statistic. RESULTS: From a
      total of 346 publications identified, 34 articles were selected for full review
      based on title and abstract. 4 RCTs comprising 576 patients (334(58%) males, mean
      age 60.7 years, age range (58-66)) met the inclusion criteria and were
      systematically reviewed. Of those, 137 (24%) patients suffered from symptomatic
      lower limb PAD. Maximum walking distances were pooled successfully from all 4
      studies. After analysing these data, we found significant heterogeneity among the
      groups and no significant difference in the pooled treatment effect (standard
      mean difference = 0.46, 95% CI (-0.99-1.92), p = 0.53, I(2); = 95%). Pain-free
      walking distances and ankle brachial pressure indices were pooled successfully
      from 3 studies and showed an insignificant overall treatment effect (standard
      mean difference = 0.97, 95% CI (-0.24-2.18), p = 0.12 and 0.68, 95% CI (-0.70
      2.06), p = 0.33, respectively). CONCLUSION: The evidence regarding ACE inhibition
      efficacy on treadmill walking distance in patients with intermittent claudication
      is contradicting and lacked properly powered RCTs. However, based on this study,
      ACEIs did not improve treadmill walking distance and ABPI in patients with
      symptomatic lower limb arterial disease. Further research from properly powered
      RCTs is needed.

PMID- 21195216
TI  - Severe osteopenia and osteoporosis, sarcopenia, and frailty status in community
      dwelling older women: results from the Women's Health and Aging Study (WHAS) II.
AB  - OBJECTIVES: The goal of this study was to examine the associations between severe
      osteopenia and osteoporosis and/or sarcopenia on frailty status, a major
      geriatric syndrome in community-dwelling older women. DESIGN: Cross-sectional
      analysis. SETTING: Women's Health and Aging Studies II (WHAS-II), Baltimore,
      Maryland. PARTICIPANTS AND MEASUREMENTS: The analytic sample for this study
      included 250 women aged 76-86 years old who underwent DXA evaluation at round 4.
      Frailty was determined using validated screening criteria. Severe osteopenia was
      defined as BMD between -2.0 SD and -2.49 SD and osteoporosis as BMD less than 
      2.5 SD (lumbar spine and/or proximal femur). Sarcopenia was determined by the
      appendicular lean mass by height(2) (aLM/ht(2) method) and considered present
      when the value was less then -2 SD compared to young women. RESULTS: Mean age of
      study subjects was 79.6 (+/-2.7) years. Overall prevalence of frailty was 6.8%
      (n=17). Severe osteopenia/osteoporosis occurred in 42.1% (n=7) in the frail
      group, 28% (n=33) in the pre frail group and 25.2% in the robust group.
      Sarcopenia was present in 52.9% (n=9) in the frail group, 42% (n=50) in the pre
      frail and 41.2% (n=47) in the robust group. Almost sixteen percent (n=39) had
      severe osteopenia/osteoporosis concomitant to sarcopenia. In an adjusted logistic
      regression model, severe osteopenia/osteoporosis (OR: 2.1; 95% CI: 0.68-6.6,
      p=0.196) and sarcopenia (OR: 3.1; 95% CI: 0.88-11.1; p=0.077) were individually
      associated with frailty, though not statistically significant. On the other hand,
      the likelihood of being frail was substantially higher in the presence of these
      two syndromes (OR: 6.4; 95% CI: 1.1-36.8, p=0.037). CONCLUSION: These findings
      suggest a concomitant impact of severe osteopenia/osteoporosis plus sarcopenia in
      regard to frailty status in a sample of oldest old women living in the community.

PMID- 21195220
TI  - Management of thoracoabdominal aortic aneurysms.

PMID- 21195221
TI  - Biothermodynamics, Part C. Preface.

PMID- 21195217
TI  - Determinants of bone mineral density in obese premenopausal women.
AB  - Despite being a risk factor for cardiovascular disease and diabetes mellitus,
      obesity has been thought to protect against osteoporosis. However, recent studies
      have demonstrated a differential impact of specific fat compartments on bone
      mineral density (BMD) with visceral adipose tissue (VAT) having potential
      detrimental effects on BMD. Visceral obesity is also associated with
      dysregulation of the GH/IGF-1 axis, an important regulator of bone homeostasis.
      The purpose of our study was to evaluate the differential effects of abdominal
      fat depots and muscle, vitamin D, and hormonal determinants, including insulin
      like growth factor-1 (IGF-1), testosterone, and estradiol, on trabecular BMD of
      the lumbar spine. We studied 68 healthy obese premenopausal women (mean BMI,
      36.7+/-4.2 kg/m(2)). Quantitative computed tomography (QCT) was used to assess
      body composition and lumbar trabecular BMD. There was an inverse association
      between BMD and VAT, independent of age and BMI (p=0.003). IGF-1 correlated
      positively with BMD and negatively with VAT and, in stepwise multivariate
      regression modeling, was the strongest predictor of BMD and procollagen type 1
      amino-terminal propeptide (P1NP). Thigh muscle cross sectional area (CSA) and
      thigh muscle density were also associated with BMD (p<0.05), but 25
      hydroxyvitamin D [25(OH)D], testosterone, free testosterone, and estradiol levels
      were not. 25(OH)D was associated inversely with BMI, total, and subcutaneous
      abdominal adipose tissue (p<0.05). These findings support the hypothesis that VAT
      exerts detrimental effects, whereas muscle mass exerts positive effects on BMD in
      premenopausal obese women. Moreover, our findings suggest that IGF-1 may be a
      mediator of the deleterious effects of VAT on bone health through effects on bone
      formation.

PMID- 21195222
TI  - Measurement and analysis of equilibrium binding titrations: A beginner's guide.
AB  - Binding events are central to biology. Simple binding of a substrate to an enzyme
      initiates catalysis. Formation of protein:protein complexes is integral to signal
      transduction. Binding of multiple proteins to the ribosomal ribonucleic acid
      (rRNA) results in ribosome assembly. Consequently, elucidation of mechanisms of
      biological processes requires binding measurements. Such measurements reveal,
      among other things, the relevant concentrations required for binding partners to
      form a complex and are indispensible to understanding the relationship between
      structure and biological function. This article is intended to serve as a primer
      for biologists who are contemplating performing binding studies. The focus is on
      practical aspects of design and analysis of binding measurements for a simple
      process. The information that one can extract from such measurements is also
      addressed. Theoretical background on binding for both simple and complex systems
      can be found in many textbooks and monographs including those by Hammes [Hammes,
      G. G. (2000). Thermodynamics and Kinetics for the Biological Sciences. Wiley, New
      York, NY], Weber [Weber, G. (1992). Protein Interactions. Chapman and Hall, New
      York, NY], and Wyman and Gill [Wyman, J. and Gill, S. J. (1990). Binding and
      Linkage. University Science Books, Mill Valley, CA]. While the first reference is
      excellent for beginners, the latter two, in addition to discussion of simple
      binding, contain theoretical background for complex binding processes.

PMID- 21195223
TI  - Macromolecular competition titration method accessing thermodynamics of the
      unmodified macromolecule-ligand interactions through spectroscopic titrations of
      fluorescent analogs.
AB  - Analysis of thermodynamically rigorous binding isotherms provides fundamental
      information about the energetics of the ligand-macromolecule interactions and
      often an invaluable insight about the structure of the formed complexes. The
      Macromolecular Competition Titration (MCT) method enables one to quantitatively
      obtain interaction parameters of protein-nucleic acid interactions, which may not
      be available by other methods, particularly for the unmodified long polymer
      lattices and specific nucleic acid substrates, if the binding is not accompanied
      by adequate spectroscopic signal changes. The method can be applied using
      different fluorescent nucleic acids or fluorophores, although the etheno
      derivatives of nucleic acid are especially suitable as they are relatively easy
      to prepare, have significant blue fluorescence, their excitation band lies far
      from the protein absorption spectrum, and the modification eliminates the
      possibility of base pairing with other nucleic acids. The MCT method is not
      limited to the specific size of the reference nucleic acid. Particularly, a
      simple analysis of the competition titration experiments is described in which
      the fluorescent, short fragment of nucleic acid, spanning the exact site-size of
      the protein-nucleic acid complex, and binding with only a 1:1 stoichiometry to
      the protein, is used as a reference macromolecule. Although the MCT method is
      predominantly discussed as applied to studying protein-nucleic acid interactions,
      it can generally be applied to any ligand-macromolecule system by monitoring the
      association reaction using the spectroscopic signal originating from the
      reference macromolecule in the presence of the competing macromolecule, whose
      interaction parameters with the ligand are to be determined.

PMID- 21195224
TI  - Analysis of PKR-RNA interactions by sedimentation velocity.
AB  - PKR is an interferon-induced kinase that plays a pivotal role in the innate
      immunity pathway for defense against viral infection. PKR is activated to undergo
      autophosphorylation upon binding to RNAs that contain duplex regions. Some highly
      structured viral RNAs do not activate and function as PKR inhibitors. In order to
      define the mechanisms of activation and inhibition of PKR by RNA, it is necessary
      to characterize the stoichiometries, affinities, and free energy couplings
      governing the assembly of the relevant complexes. We have found sedimentation
      velocity analytical ultracentrifugation to be particularly useful in the study of
      PKR-RNA interactions. Here, we describe protocols for designing and analyzing
      sedimentation velocity experiments that are generally applicable to studies of
      protein-nucleic acid interactions. Initially, velocity data obtained at multiple
      protein:RNA ratios are analyzed using the dc/dt method's to define the
      association model and to test whether the system is kinetically limited. The
      sedimentation velocity data obtained at multiple loading concentrations are then
      globally fitted to this model to determine the relevant association constants.
      The frictional ratios of the complexes are calculated using the fitted
      sedimentation coefficients to determine whether the hydrodynamic properties are
      physically reasonable. We demonstrate the utility of this approach using examples
      from our studies of PKR interactions with simple dsRNAs, the HIV TAR RNA, and the
      VAI RNA from adenovirus.

PMID- 21195225
TI  - Structural and thermodynamic analysis of PDZ-ligand interactions.
AB  - Tiam-family guanine exchange proteins are activators of the Rho GTPase Rac1 and
      critical for cell morphology, adhesion, migration, and polarity. These modular
      proteins contain a variety of signaling domains, including a single postsynaptic
      density-95/discs large/zonula occludens-1 (PDZ) domain. Here, we show how
      structural and thermodynamic approaches applied to the Tiam1 PDZ domain can be
      used to gain unique insights into the affinity and specificity of PDZ-ligand
      interactions with peptides derived from Syndecan1 and Caspr4 proteins. First, we
      describe a fluorescence anisotropy-based assay that can be used to determine PDZ
      ligand interactions, and describe important considerations in designing binding
      experiments. Second, we used site-specific mutagenesis in combination with double
      mutant cycle analysis to probe the binding energetics and cooperativity of
      residues in two ligand binding pockets (S(0) and S(-2)) that are involved in
      Tiam1 PDZ-ligand interactions. Peptide ligand binding results and double-mutant
      cycle analysis revealed that the S(0) pocket was important for Syndecan1 and
      Caspr4 peptide interactions and that the S(-2) pocket provided selectivity for
      the Syndecan1 ligand. Finally, we devised a "peptide evolution" strategy whereby
      a Model consensus peptide was "evolved" into either the Syndecan1 or Caspr4
      peptide by site-directed mutagenesis. These results corroborated the PDZ
      mutational analysis of the S(0) pocket and identified the P(-4) position in the
      ligand as critical for Syndecan1 affinity and selectivity. Together, these
      studies show that a combined structural and thermodynamic approach is powerful
      for obtaining insights into the origin of Tiam1 PDZ-ligand domain affinity and
      specificity.

PMID- 21195226
TI  - Thermodynamic analysis of metal ion-induced protein assembly.
AB  - A large number of biological systems are regulated by metal ion-induced protein
      assembly. This phenomenon can play a critical role in governing protein function
      and triggering downstream biological responses. We discuss the basic
      thermodynamic principles of linked equilibria that pertain to metal ion-induced
      dimerization and describe experimental approaches useful for studying such
      systems. The most informative techniques for studying these systems are
      sedimentation velocity and sedimentation equilibrium analytical
      ultracentrifugation, although a wide range of other spectroscopic,
      chromatographic, or qualitative approaches can provide a wealth of useful
      information. These experimental procedures are illustrated with examples from two
      systems currently under study: zinc-induced assembly of a staphylococcal protein
      responsible for intercellular adhesion in bacterial biofilms and calcium-induced
      dimerization of a human nucleotidase.

PMID- 21195227
TI  - Thermodynamic dissection of colicin interactions.
AB  - Bacteriocins are selective protein antibiotics that bind and kill specific
      bacterial species, the best studied of which are the colicins that target
      Escherichia coli. Colicins tend to parasitize cell envelope systems that are
      important for cell viability under nutrient-limited conditions or environmental
      stress. In this chapter, we review how in conjunction with other biophysical
      methods and structural information, isothermal titration calorimetry (ITC) has
      been used to investigate how colicins enter E. coli cells. In particular, we
      summarize current understanding of the thermodynamics of outer membrane receptor
      binding and how this has been linked to biological function. We also summarize
      thermodynamic investigations using ITC that have helped elucidate the mechanisms
      by which colicins bind and parasitize proteins in the periplasm, forming protein
      protein interactions that ultimately trigger translocation across the outer
      membrane. Our review focuses on the two major cytotoxic classes of colicin that
      have been the subject of intense investigation, pore-forming toxins, and
      nonspecific endonucleases (DNases). DNase colicin-producing E. coli avoid
      committing suicide through the production of a small antidote protein known as
      the immunity (Im) protein, with the Im protein only released once cell-entry is
      initiated. Exosite binding by Im proteins has driven an evolutionary arms race
      among colicin-producing bacteria whereby markedly different colicin DNase-Im
      protein interaction specificities have evolved without impacting on cytotoxicity.
      Extensive investigations have shown that homologous colicin DNase-Im protein
      complexes have K(d)s, for cognate and noncognate complexes, that vary by 10
      orders of magnitude, essentially matching the entire spectrum of binding
      affinities seen for protein-protein interactions in biology. Hence, this system
      has proved to be a powerful model for investigating the thermodynamics of
      specificity in protein-protein interactions, with ITC being the principal tool.
      We review this literature and point to how the thermodynamic information that has
      been generated complements various other kinetic and structural data.

PMID- 21195228
TI  - Energetics of Src homology domain interactions in receptor tyrosine kinase
      mediated signaling.
AB  - Intracellular signaling from receptor tyrosine kinases (RTK) on extracellular
      stimulation is fundamental to all cellular processes. The protein-protein
      interactions which form the basis of this signaling are mediated through a
      limited number of polypeptide domains. For signal transduction without
      corruption, based on a model where signaling pathways are considered as linear
      bimolecular relays, these interactions have to be highly specific. This is
      particularly the case when one considers that any cell may have copies of similar
      binding domains found in numerous proteins. In this work, an overview of the
      thermodynamics of binding of two of the most common of these domains (SH2 and SH3
      domains) is given. This, coupled with insight from high-resolution structural
      detail, provides a comprehensive survey of how recognition of cognate binding
      sites for these domains occurs. Based on the data presented, we conclude that
      specificity offered by these interactions of SH2 and SH3 domains is limited and
      not sufficient to enforce mutual exclusivity in RTK-mediated signaling. This may
      explain the current lack of success in pharmaceutical intervention to inhibit the
      interactions of these domains when they are responsible for aberrant signaling
      and the resulting disease states such as cancer.

PMID- 21195229
TI  - Structural and functional energetic linkages in allosteric regulation of muscle
      pyruvate kinase.
AB  - The understanding of the molecular mechanisms of allostery in rabbit muscle
      pyruvate kinase (RMPK) is still in its infancy. Although, there is a paucity of
      knowledge on the ground rules on how its functions are regulated, RMPK is an
      ideal system to address basic questions regarding the fundamental chemical
      principles governing the regulatory mechanisms about this enzyme which has a TIM
      (alpha/beta)(8) barrel structural motif [Copley, R. R., and Bork, P. (2000).
      Homology among (betaalpha)8 barrels: Implications for the evolution of metabolic
      pathways. J. Mol. Biol.303, 627-640; Farber, G. K., and Petsko, G. A. (1990). The
      evolution of alpha/beta barrel enzymes. Trends Biochem.15, 228-234; Gerlt, J. A.,
      and Babbitt, P. C. (2001). Divergent evolution of enzymatic function:
      Mechanistically diverse superfamilies and functionally distinct superfamilies.
      Annu. Rev. Biochem.70, 209-246; Heggi, H., and Gerstein, M. (1999). The
      relationship between protein structure and function: A comprehensive survey with
      application to the yeast genome. J. Mol. Biol.288, 147-164; Wierenga, R. K.
      (2001). The TIM-barrel fold: A versatile framework for efficient enzymes. FEB
      Lett.492, 193-198]. RMPK is a homotetramer. Each subunit consists of 530 amino
      acids and multiple domains. The active site resides between the A and B domains.
      Besides the basic TIM-barrel motif, RMPK also exhibits looped-out regions in the
      alpha/beta barrel of each monomer forming the B- and C-domains. The two isozymes
      of PK, namely, the kidney and muscle isozymes, exhibit very different allosteric
      behaviors under the same experimental condition. The only amino acid sequence
      differences between the mammalian kidney and muscle PK isozymes are located in
      the C-domain and are involved in intersubunit interactions. Thus, embedded in
      these two isozymes of PK are the rules involved in engineering the popular TIM
      (alpha/beta)(8) motif to modulate its allosteric properties. The PK system
      exhibits a lot of the properties that will allow mining of the ground rules
      governing the correlative linkages between sequence-fold-function. In this
      chapter, we review the approaches to acquire the fundamental functional and
      structural energetics that establish the linkages among this intricate network of
      linked multiequilibria. Results from these diverse approaches are integrated to
      establish a working model to represent the complex network of multiple linked
      reactions which ultimately leads to the observation of allosteric regulation of
      PK.

PMID- 21195230
TI  - Analysis of free energy versus temperature curves in protein folding and
      macromolecular interactions.
AB  - Plots of free energy versus temperature are commonly called stability curves or
      Gibbs-Helmholtz curves, and they have proven to be extremely useful in protein
      folding and ligand-binding studies. Curvature in a Gibbs-Helmholtz or stability
      plot is indicative of a heat capacity change, and some of their primary uses in
      biochemistry over the past few decades have included determining DeltaCp values
      and comparing DeltaCp values between two related processes. This chapter
      describes basic approaches for analyzing curved Gibbs-Helmholtz plots, along with
      two specific extensions of standard Gibbs-Helmholtz plot analysis: (1)
      translating DeltaG of folding versus temperature into DeltaH and DeltaS versus
      temperature for comparing mesophilic-thermophilic protein pairs, and (2) fitting
      Gibbs-Helmholtz plots to determine if DeltaCp changes with temperature or not.
      Neither of these extensions is new, but they are infrequently used, and their use
      is particularly germane to certain molecular interpretations of thermodynamic
      information from DeltaG versus temperature curves. It is shown that translating
      DeltaG of folding into DeltaH and DeltaS of folding versus temperature for a
      mesophilic-thermophilic protein pair can immediately influence possible
      structural hypotheses for thermal stabilization of thermophilic proteins. It is
      also shown that very small temperature-dependent heat capacity changes
      (DeltaDeltaCp values) can be obtained from extended fits to DeltaG versus
      temperature plots, and that these very small DeltaDeltaCp values can have serious
      consequences for any attempt to correlate DeltaCp with DeltaASA for some
      reactions.

PMID- 21195231
TI  - Application of the sequential n-step kinetic mechanism to polypeptide
      translocases.
AB  - Clp/Hsp100 proteins are essential motor proteins in protein quality control
      pathways in all organisms. Such enzymes couple the energy derived from ATP
      binding and hydrolysis to translocate and unfold polypeptide substrates. Often
      they perform this role in collaboration with proteases for protein removal or
      with other chaperones for protein disaggregation. Unlike other well-characterized
      motor proteins, fundamental parameters such as the microscopic rate constants and
      overall rate of translocation, step-size (amino acids translocated per step),
      processivity, and directionality are not available for many of these enzymes. We
      have recently developed a fluorescence stopped-flow method to elucidate these
      fundamental mechanistic details. In addition, we have developed a quantitative
      method to examine the single-turnover time courses that result from the rapid
      mixing experiments. With these two advances in hand, we have recently reported
      the first determination of the microscopic rate constants, overall rate of
      translocation, kinetic step-size, and processivity for the E. coli ClpA
      polypeptide translocase. Here, we report a description of both the fluorescence
      stopped-flow method to examine the mechanism of enzyme catalyzed polypeptide
      translocation and the mathematics required to quantitatively examine the
      resulting time courses.

PMID- 21195232
TI  - A coupled equilibrium approach to study nucleosome thermodynamics.
AB  - The repeating structural unit of eukaryotic chromatin, the nucleosome, is
      composed of two copies each of the histone proteins H2A, H2B, H3, and H4. These
      proteins form an octamer around which 147bp of DNA is wrapped in 1.65
      superhelical turns (Luger et al., 1997). The nucleosome represents a major
      obstacle for any protein seeking access to the DNA. Several strategies have
      evolved to regulate access to nucleosomal DNA, such as posttranslational
      modification of histones and histone variants, ATP-dependent chromatin remodeling
      machines, and histone chaperones. It is likely that most if not all of these
      mechanisms directly impact the thermodynamics of the nucleosome. The DNA sequence
      itself may also impact its own inherent accessibility through modulating
      nucleosome positioning and/or thermodynamics. However, these working hypotheses
      could not be tested directly because no assays to measure nucleosome stability
      under physiological conditions were available. Attempts to determine the
      stability of nucleosomes have been hampered by the fact that the nucleosomes do
      not assemble in vitro under physiological conditions, but will only form
      nucleosomes through titration from high (2M) to low (>0.3M) ionic strength. We
      have developed a coupled equilibrium approach using the histone chaperone Nap1 to
      measure nucleosome thermodynamics under physiological conditions. This method
      will be useful for examining the impact of DNA sequence, histone variants, and
      posttranslational modifications on nucleosome thermodynamics.

PMID- 21195234
TI  - A new year in medicine.

PMID- 21195235
TI  - On synthetic biology.

PMID- 21195236
TI  - A breath of fresh indoor air.

PMID- 21195233
TI  - Quantitative methods for measuring DNA flexibility in vitro and in vivo.
AB  - The double-helical DNA biopolymer is particularly resistant to bending and
      twisting deformations. This property has important implications for DNA folding
      in vitro and for the packaging and function of DNA in living cells. Among the
      outstanding questions in the field of DNA biophysics are the underlying origin of
      DNA stiffness and the mechanisms by which DNA stiffness is overcome within cells.
      Exploring these questions requires experimental methods to quantitatively measure
      DNA bending and twisting stiffness both in vitro and in vivo. Here, we discuss
      two classical approaches: T4 DNA ligase-mediated DNA cyclization kinetics and lac
      repressor-mediated DNA looping in Escherichia coli. We review the theoretical
      basis for these techniques and how each can be applied to quantitate biophysical
      parameters that describe the DNA polymer. We then show how we have modified these
      methods and applied them to quantitate how apparent DNA physical properties are
      altered in vitro and in vivo by sequence-nonspecific architectural DNA-binding
      proteins such as the E. coli HU protein and eukaryotic HMGB proteins.

PMID- 21195237
TI  - Will an aspirin a day help keep fatal cancer away?

PMID- 21195239
TI  - Clare Gerada: Chair of UK's Royal College of General Practitioners.

PMID- 21195240
TI  - Oral sucrose for procedural pain in infants.

PMID- 21195241
TI  - Oral sucrose for procedural pain in infants.

PMID- 21195242
TI  - Oral sucrose for procedural pain in infants.

PMID- 21195243
TI  - Oral sucrose for procedural pain in infants.

PMID- 21195244
TI  - Oral sucrose for procedural pain in infants.

PMID- 21195246
TI  - International response to Niger's hunger crisis.

PMID- 21195247
TI  - The Greek economic crisis: a primary health-care perspective.

PMID- 21195248
TI  - When will the sun shine on Cyprus's National Health Service?

PMID- 21195249
TI  - All important contributions to papers should be recognised.

PMID- 21195250
TI  - Reporting on the modes of data collection.

PMID- 21195251
TI  - Borderline personality disorder.
AB  - Recent research findings have contributed to an improved understanding and
      treatment of borderline personality disorder. This disorder is characterised by
      severe functional impairments, a high risk of suicide, a negative effect on the
      course of depressive disorders, extensive use of treatment, and high costs to
      society. The course of this disorder is less stable than expected for personality
      disorders. The causes are not yet clear, but genetic factors and adverse life
      events seem to interact to lead to the disorder. Neurobiological research
      suggests that abnormalities in the frontolimbic networks are associated with many
      of the symptoms. Data for the effectiveness of pharmacotherapy vary and evidence
      is not yet robust. Specific forms of psychotherapy seem to be beneficial for at
      least some of the problems frequently reported in patients with borderline
      personality disorder. At present, there is no evidence to suggest that one
      specific form of psychotherapy is more effective than another. Further research
      is needed on the diagnosis, neurobiology, and treatment of borderline personality
      disorder.

PMID- 21195252
TI  - Killing two birds with one stone.

PMID- 21195253
TI  - Lip pressure at rest and during function in 2 groups of patients with different
      occlusions.
AB  - INTRODUCTION: The influence of the forces exerted by the perioral musculature on
      the position of the teeth has been the object of many scientific studies. Of the
      forces from the soft tissues, those from the tissues in the passive resting state
      are believed to be more important than forces exerted on the teeth during various
      functions such as speech and swallowing. The aims of this study were to measure
      upper lip pressure at rest and during swallowing in 2 groups of patients with
      different occlusions and to evaluate any differences among the groups. METHODS:
      Fifty subjects were divided into 2 groups according to occlusal and skeletal
      patterns: Class I and Class II. Both groups were divided into 2 subgroups
      according to age: young patients (9-17 years) and adult patients (18-35 years). A
      force-sensing resistor device (Datalog, Flexiforce low type, Biometrics Ltd,
      Gwent, United Kingdom) with a transducer thickness of less of 1 mm was used for
      the measurements. The sensor was positioned on the midline between the maxillary
      incisors with a thin layer of soft wax. Labial pressure measurements were made
      with the lips at rest and during swallowing saliva. RESULTS: The average resting
      lip pressure was 24.59 +/- 2.55 g/cm(2); during swallowing, the mean pressure was
      24.87 +/- 2.45 g/cm(2). No significant difference was found between lip pressure
      at rest and at function or between the two groups with different occlusions and
      skeletal patterns. There was a significant correlation between lip pressure and
      age. CONCLUSIONS: In healthy patients, (1) upper lip pressure does not change at
      rest and during swallowing, (2) upper lip pressure was similar in the 2 groups
      (Class I, 24.33 g/cm(2); Class II, 24.61 g/cm(2)), and (3) lip pressure was
      higher in adults than in young subjects. Further studies are needed to measure
      the pressure of the lower lip and to evaluate whether there are differences in
      labial pressure between subjects with labial competence and incompetence.

PMID- 21195254
TI  - Integration of parts in the facial skeleton and cervical vertebrae.
AB  - INTRODUCTION: The purpose of this study was to undertake an exploratory analysis
      of the relationship among parts in the facial skeleton and cervical vertebrae and
      their integration as 2-dimensional shapes by determining their individual
      variations and covariations. The study was motivated by considerations applicable
      to clinical orthodontics and maxillofacial surgery, in which such relationships
      bear directly on pretreatment analysis and assessment of posttreatment outcome.
      METHODS: Lateral radiographs of 61 adolescents of both sexes without major
      malocclusions were digitized and marked up by using continuous outline spline
      curves for 8 defined parts in the facial skeleton, including the cervical
      vertebrae. Individual part variation was analyzed by using principal components
      analysis, and paired part covariation was analyzed by using 2-block partial least
      squares analysis in 2 modes: relative size, position, and shape; and shape only.
      RESULTS: For individual part variations, cranial base, soft-tissue profile, and
      mandible had the largest variations across the sample. For covariation of
      relative size, position, and shape, the cervical vertebrae were highly correlated
      with the cranial base (r = 0.80), nasomaxillary complex (r = 0.70), mandible (r =
      0.74), maxillary dentition (r = 0.70), and mandibular dentition (r = 0.74); the
      maxillary dentition and mandibular dentition were highly correlated (r = 0.70);
      the mandible was highly correlated with the bony profile (r = 0.72), soft-tissue
      profile (r = 0.79), and, to a lesser extent, the cranial base (r = 0.67); the
      bony profile was highly correlated with the cranial base (r = 0.70) and soft
      tissue profile (r = 0.80); the soft-tissue profile was highly correlated with the
      nasomaxillary dentition (r = 0.81). Covariation of shape only was much weaker
      with significant covariations found between bony profile and mandible (r = 0.53),
      bony profile and mandibular dentition (r = 0.65), mandibular dentition and soft
      tissue profile (r = 0.54), mandibular dentition and maxillary dentition (r =
      0.55), and bony profile and soft-tissue profile (r = 0.69). CONCLUSIONS: We found
      that integration of the shape of parts in the facial skeleton and cervical
      vertebrae is weak; it is the relative size, position, and orientation of parts
      that form the strongest correlations.

PMID- 21195255
TI  - Mechanical effects of third-order movement in self-ligated brackets by the
      measurement of torque expression.
AB  - INTRODUCTION: Axial rotation of orthodontic wire produces buccal or lingual root
      movement and is often referred to as third-order movement or "torque expression."
      The objective of this study was to quantify torque expression in 3 self-ligation
      bracket systems (Damon Q, Ormco, Orange, Calif; In-Ovation R, GAC, Bohemia, NY;
      and Speed, Strite Industries, Cambridge, Ontario, Canada) during loading and
      unloading. METHODS: A stepper motor was used to rotate a wire in a fixed bracket
      slot from -15 degrees  to 63 degrees  in 3 degrees  increments, and then back to 
      15 degrees . The bracket was mounted on top of a load cell that measured forces
      and moments in all directions. RESULTS: Damon's and In-Ovation's maximum average
      torque values at 63 degrees  were 105 and 113 Nmm, respectively. Many Speed
      brackets experienced premature loss of torque between 48 degrees  and 63 degrees
      , and the average maximum was 82 Nmm at 54 degrees . The torque plays for Damon,
      In-Ovation, and Speed were 11.3 degrees , 11.9 degrees , and 10.8 degrees ,
      respectively. CONCLUSIONS: Generally, In-Ovation expressed the most torque at a
      given angle of twist, followed by Damon and then Speed. However, there was no
      significant difference between brackets below 34 Nmm of torque. From a clinical
      perspective, the torque plays between brackets were virtually indistinguishable.

PMID- 21195256
TI  - Treatment of posterior crossbite comparing 2 appliances: a community-based trial.
AB  - INTRODUCTION: The aim of this community-based trial was to compare the
      effectiveness of the quad-helix appliance and removable plates for treating
      posterior crossbite. METHODS: Ninety-nine patients were randomly divided into 3
      groups: quad-helix, expansion plate, and untreated. All subjects were in the
      mixed dentition, had posterior crosssbite, no sucking habits, no previous
      orthodontic treatment, and no Class III malocclusion. The following aspects were
      evaluated: posterior crossbite correction, maxillary and mandibular intermolar
      and intercanine expansions, length of treatment, cost-benefit analysis, success
      rate, and number of complications. RESULTS: The length of treatment and the costs
      were higher in the expansion plate group than in the quad-helix group. The
      success rates were similar for the quad-helix and the expansion plate groups, and
      the number of complications was higher in the quad-helix group. No self
      correction was observed in the untreated group, and relapses occurred in both
      experimental groups. CONCLUSIONS: The average treatment time was significantly
      shorter and 11% less expensive than in the quad-helix group, making it the more
      cost-effective choice for treatment.

PMID- 21195257
TI  - Effects of analgesics on orthodontic pain.
AB  - INTRODUCTION: Our objective was too assess the effectiveness of 3 analgesics
      (ibuprofen, naproxen sodium, and acetaminophen) and a placebo administered before
      and after the placement of separators in reducing the severity of postseparator
      placement pain. We also examined the impact of treatment on chewing efficiency at
      24 hours after separator placement. METHODS: Twenty-four subjects participated in
      the study. Each subject received 3 of 4 treatments: ibuprofen, naproxen sodium,
      acetaminophen, or placebo in random order at monthly intervals. The dosing times
      were 1 hour before separator placement and 3 and 7 hours after separator
      placement. Before placement, the subjects completed a masticatory efficiency test
      and a visual analog scale (VAS) for expected pain and pain experienced. A VAS
      pain diary was kept for 24 hours. Subjects returned to the clinic after 1 week
      for separator removal. RESULTS: VAS pain summary scores after separator placement
      were significantly affected by the administration of ibuprofen (P = 0.0298) and
      the time after separator placement (P <0.0001). Administering ibuprofen before
      and after separator placement significantly reduced pain compared with the
      placebo. The analgesic effects diminished by day 2, resulting in peak pain levels
      and decreased chewing efficiency. The expected pain after separator placement
      also played a role in experienced pain; subjects expecting more pain experienced
      more pain. CONCLUSIONS: Ibuprofen was superior to the placebo in relieving
      postseparator pain as measured by the VAS pain summary scores, whereas
      acetaminophen and naproxen sodium did not significantly differ from the placebo.

PMID- 21195258
TI  - Three-dimensional modeling and finite element analysis in treatment planning for
      orthodontic tooth movement.
AB  - INTRODUCTION: The objective of this study was to demonstrate the potential of 3
      dimensional modeling and finite element analysis as clinical tools in treatment
      planning for orthodontic tooth movement. High stresses in bone and miniscrew
      implants under load can cause fractures and trauma for orthodontic patients, and
      treatments are typically planned by using clinical experience or simple 2
      dimensional radiographs. METHODS: Anatomically accurate 3-dimensional models
      reconstructed from cone-beam computed tomography scans were used to simulate the
      retraction of a single-rooted mandibular canine with a miniscrew placed as
      skeletal anchorage. Detailed stress distributions in the implant and peri-implant
      bone were found, in addition to the effect of the orthodontic bracket hook length
      and the angulation of retraction force on stress response in the periodontal
      ligament (PDL). RESULTS: The numeric results showed that the equivalent von Mises
      stress on the miniscrew under a 200-cN tangential load reached 42 MPa at the
      first thread recession, whereas von Mises stress in the peri-implant bone only
      reached 11 MPa below the neck. High tightening loads of 200 N.mm of torsion and
      460 cN of axial compression resulted in much greater bone and implant von Mises
      stresses than tangential loading, exceeding the yield strengths of the titanium
      alloy and the cortical bone. Increasing the hook length on the orthodontic
      bracket effectively reduced the canine PDL stress from 80 kPa with no hook to 22
      kPa with a hook 7 mm long. Angulating the force apically downward from 0 degrees 
      to 30 degrees  had a less significant effect on the PDL stress profile and
      initial canine deflection. The results suggest that stresses on miniscrew
      implants under load are sensitive to changes in diameter. Overtightening a
      miniscrew after placement might be a more likely cause of fracture failure and
      bone trauma than application of tangential orthodontic force. The reduction of
      stress along the PDL as a result of increasing the bracket hook length might
      account for steadier tooth translation by force application closer to the center
      of resistance of a single-rooted canine. The relatively minor effect of force
      angulation on the PDL response suggests that the vertical placement of miniscrews
      in keratinized or nonkeratinized tissue might not significantly affect
      orthodontic tooth movement. CONCLUSIONS: This model can be adapted as a patient
      specific clinical orthodontic tool for planning movement of 1 tooth or several
      teeth.

PMID- 21195259
TI  - Electron-beam irradiation of polymer bracket materials.
AB  - INTRODUCTION: Electron-beam irradiation can be used to influence the properties
      of polymers. Electron beams cause cross-linking that enhances the molecular mass
      of the polymer; this leads to branched chains until, ultimately, a 3-dimensional
      network is formed. The aim of this study was to evaluate the effect of electron
      beam irradiation on polymer bracket materials. METHODS: Since polymers are
      commonly used materials for brackets, polyoxymethylene, polycarbonate, and
      polyurethane were chosen for this study. The acceleration voltage of the electron
      beam device was 10 MeV, and the energy dose was 100 kGy with an electron
      accelerator (BGS beta gamma service, Rhodotron, Bruchsal, Germany). Three-medium
      wear, fracture toughness, and Vickers hardness tests were performed. The
      irradiated samples were compared with untreated control groups. RESULTS:
      Polycarbonate and polyurethane bracket materials have enhanced fracture toughness
      and Vickers hardness after electron-beam irradiation of 100 kGy and 10 MeV.
      Polyoxymethylene bracket materials showed significantly lower fracture toughness
      values after irradiation compared with the untreated control group.
      Polyoxymethylene had the best mechanical properties, followed by polycarbonate
      and polyurethane. Almost the same effects could be measured during the 3-medium
      wear test. CONCLUSIONS: Electron-beam postcuring improved Vickers hardness and
      fracture toughness of polymers with lower mechanical properties (polycarbonate
      and polyurethane). Polyoxymethylene, with sufficient hardness and fracture
      toughness, could not be improved with electron-beam postcuring.

PMID- 21195260
TI  - Stability of unilateral posterior crossbite correction in the mixed dentition: a
      randomized clinical trial with a 3-year follow-up.
AB  - INTRODUCTION: The long-term stability of posterior crossbite correction in the
      mixed dentition has not been sufficiently evaluated. Our aim was to compare long
      term outcomes in patients with crossbite correction by using matched controls
      with normal occlusion. METHODS: After 35 patients were treated for crossbite with
      a quad-helix or an expansion plate, we used randomized controlled trial
      methodology to follow them for 3 years posttreatment. All had fulfilled our
      pretreatment criteria: mixed dentition, unilateral posterior crossbite, no
      sucking habits, and no previous orthodontic treatment. Transverse relationships,
      maxillary and mandibular widths, overbite, overjet, arch lengths, and midlines
      were registered on the study models immediately before and after treatment and at
      the follow-up 3 years after treatment. The matched control group comprised 20
      subjects with normal occlusion and was compared with the first and last
      registrations for the treated groups. RESULTS: At follow-up, changes in the
      treatment groups were equal and stable. The changes were comparable with the
      control group. All other changes were minor and had no clinical implications. The
      long-term effect of crossbite correction on midline deviation was unpredictable.
      CONCLUSIONS: If crossbite is successfully corrected by the quad-helix appliance
      or the expansion plate, similar long-term stability is achieved. However, in
      treated patients, mean maxillary widths never reached those of normal control
      subjects.

PMID- 21195261
TI  - Drift characteristics of miniscrews and molars for anchorage under orthodontic
      force: 3-dimensional computed tomography registration evaluation.
AB  - INTRODUCTION: Although miniscrews have been used as absolute anchorage for a long
      time, their behavior under orthodontic loading is still unclear clinically.
      Therefore, this study was designed to evaluate the behavior of miniscrews under
      loading by retrospective 3-dimensional registration. METHODS: Sixty adult
      patients who had miniscrews as anchorage for en-masse retraction of anterior
      teeth were studied. Computerized tomography scans were made before force
      application and after closure of the extraction spaces, respectively. The 3
      dimensional reconstruction and registration of before and after computerized
      tomography data were performed to assess the displacement of the miniscrews,
      first molars, and maxillary central incisors. RESULTS: The miniscrews and the
      maxillary first molars drifted mesially 0.23 and 0.91 mm apically, and 0.23 and
      0.92 mm coronally; the amounts of maxillary incisor retraction at the edge and
      the apex were 5.94 and 1.40 mm, respectively, with 1.84 mm of maxillary central
      incisor intrusion. CONCLUSIONS: Our results indicated that the miniscrews and the
      maxillary first molars were mesially displaced under orthodontic loading. A
      mesial site for miniscrews might be a better choice for long-term stability.

PMID- 21195262
TI  - Smile esthetics from the layperson's perspective.
AB  - INTRODUCTION: Computer-based smile esthetic surveys based on slider technology
      allow more precise control of variables and the possibility of obtaining
      continuous data. Variations in the perception of smiles from different facial
      perspectives have not been resolved. The objective of this study was to quantify
      the ideal and the range of acceptable values for smile variables judged by
      laypersons from a full-face perspective for comparison with lower-face data.
      METHODS: Mirrored and symmetric male and female full faces previously determined
      by peers to be of average attractiveness were used. Ninety-six laypersons judged
      these smile variables: smile arc, buccal corridor fill, maxillary gingival
      display, maxillary midline to face, maxillary to mandibular midline discrepancy,
      overbite, central incisor gingival margin discrepancy, maxillary anterior
      gingival height discrepancy, incisal edge discrepancy, and cant. The judges
      manipulated the variables using adjustable image technology that allowed the
      variable to morph and appear continuous on a computer monitor. Medians for each
      smile variable were compiled, and the Fleiss-Cohen weighted kappa statistic was
      calculated to measure reliability. Multiple randomization tests with adjusted P
      values were used to compare these data with those for lower-face views. RESULTS:
      Reliability ranged from 0.25 for ideal overbite to 0.60 for upper midline to
      face, except for upper and lower buccal corridor limits, which each had a kappa
      value near 0. There were no statistically significant differences between the
      ratings of male and female raters. The following variables showed statistically
      and clinically significant differences (>1 mm) when compared with the lower-face
      view: ideal smile arc, ideal buccal corridor, maximum gingival display, upper to
      lower midline, and occlusal cant. Although the smile arc values differed because
      of model lip curvature variations, the principle of tracking the curve of the
      lower lip was confirmed. For the full-face view, the raters preferred less
      maximum gingival display, less buccal corridor, more upper to lower midline
      discrepancy, and less cant of the occlusal plane. CONCLUSIONS: Reliability was
      fair to moderate with the exception of the buccal corridor limits. Most variables
      showed no clinically meaningful differences from the lower-face view. The
      acceptable range was quite large for most variables. Detailed knowledge of the
      ideal values of the various variables is important and can be incorporated into
      orthodontic treatment to produce an optimal esthetic smile.

PMID- 21195264
TI  - About light and shadow.

PMID- 21195266
TI  - Lack of evidence forces practitioners to make clinically based decisions.

PMID- 21195268
TI  - Academic impropriety.

PMID- 21195270
TI  - Relationship between occlusion and temporomandibular disorders: implications for
      the gnathologist.

PMID- 21195271
TI  - Relationship between occlusion and temporomandibular disorders: Implications for
      the orthodontist.

PMID- 21195272
TI  - Survey of orthodontic residency programs: teaching about occlusion,
      temporomandibular joints, and temporomandibular disorders in postgraduate
      curricula.
AB  - INTRODUCTION: Teaching orthodontic postgraduate students about occlusion and the
      temporomandibular joint is a fundamental component of their education, but
      faculty members are confronted with disputes and controversies about these
      topics. The purpose of this study was to ascertain where the orthodontic teaching
      community currently stands on the topics of occlusion, temporomandibular joint,
      and temporomandibular disorder. METHODS: A 46-question survey was sent to every
      orthodontic program director in the United States and Canada (n = 69). Responses
      were submitted by 46, and the results were tabulated. RESULTS: Three interrelated
      topics (normal or ideal temporomandibular joint, normal or ideal occlusion, and
      management of temporomandibular disorder) are being taught in diverse ways in
      these postgraduate orthodontic programs. CONCLUSIONS: The results of this survey
      will help us to understand and improve how these topics are being taught at
      accredited orthodontic programs in the United States and Canada. Perhaps a
      standardized curriculum can be developed.

PMID- 21195273
TI  - Effectiveness of orthodontic treatment with functional appliances on mandibular
      growth in the short term.
AB  - INTRODUCTION: The aim of this study was to analyze the current literature for the
      best evidence (randomized clinical trials) about the efficacy of functional
      appliances on mandibular growth in the short term. METHODS: A survey of articles
      published up to September 2009 was performed by using the following electronic
      databases: PubMed, Embase, Ovid Medline, Cochrane Central Register of Controlled
      Trials, Web of Science, LILACS, and Google Scholar. The reference lists of the
      retrieved articles were hand-searched for possible missing articles. No language
      restriction was applied during the identification of the published studies. A
      methodologic scoring process was developed to identify which randomized clinical
      trials were stronger methodologically. The selection process and the quality
      assessment were undertaken independently and in duplicate by 2 authors. A meta
      analysis was attempted by using random-effects models. Clinical and statistical
      heterogeneity was examined, and a sensitivity analysis was performed. RESULTS:
      Electronic searches identified the following items: 146 articles were retrieved
      from PubMed, 45 from Cochrane Central Register of Controlled Trials, 29 from
      Ovid, 42 from LILACS, 628 from Web of Science, and 1000 from Google Scholar.
      Thirty-two articles fulfilled the specific inclusion criteria and were identified
      as potentially appropriate randomized clinical trials to be included in this meta
      analysis. Only 4 articles, based on data from 338 patients (168 treated vs 170
      controls) with Class II malocclusion in the mixed dentition, were selected for
      the final analysis. The quality analysis of these studies showed that the
      statistical methods were at the medium-high level. The outcome measurements
      chosen to evaluate the efficacy of the various functional appliances were Co-Pg,
      Pg/Olp + Co/Olp, and Co-Gn and the values were annualized and standardized to a
      uniform scale with the standardized mean differences (SMD). The results of the
      meta-analysis from the random-effects model showed a statistically significant
      difference of 1.79 mm in annual mandibular growth of the treatment group compared
      with the control group (SMD = 0.61, 95% CI, 0.30 to -0.93; chi-square test, 5.34;
      3 df; P = 0.15; I(2) = 43.9%; test for overall effect, Z = 3.83 and P = 0.0001).
      The sensitivity analysis showed a substantially similar outcome of 1.91 mm (SMD =
      0.65, 95% CI, 0.25 to 1.25; chi-square test, 4.96; 2 df; P = 0.08; I(2) = 59.7%;
      test for overall effect, Z = 3.19 and P = 0.001). CONCLUSIONS: The analysis of
      the effect of treatment with functional appliances vs an untreated control group
      showed that skeletal changes were statistically significant, but unlikely to be
      clinically significant.

PMID- 21195274
TI  - Orthodontic tooth movement: bone formation and its stability over time.
AB  - INTRODUCTION: Orthodontic tooth movement can lead to the creation of bone. The
      purposes of the study were to investigate the amount of bone formed in
      orthodontic patients during treatment (maxillary canine distalization) and
      retention and to assess the long-term stability of the new bone. METHODS: The
      sample consisted of 80 patients with 128 missing lateral incisors who were
      treated with distalization of the maxillary canines. They were examined at the
      beginning of orthodontic treatment (T1), at the end of treatment (T2), 2 years
      after treatment (T3A), and 5 years after treatment (T3B). The influence of the
      canine's inclination and its distance from the central incisor at T1 on the
      amount of bone created and the bone mass stability over time were assessed.
      Vestibular width of the alveolus was measured on casts at the level of the bone
      ridge and 5 mm apically from the alveolar ridge. Canine inclination to the
      alveolar ridge was recorded, as well as the height of the alveolar ridge.
      RESULTS: During treatment, T1 to T2, the alveolar ridge width was reduced by 4%,
      and the height decreased by 0.26 mm; during the retention periods (T2-T3A, T2
      T3B), the alveolar ridge reduction was 2% on average, with individual variances,
      and height decreased by 0.38 mm on average. No correlation was found between
      canine inclination or between the canine distance from the central incisor at T1
      and the amount and stability of the bone created by the orthodontic movement.
      CONCLUSIONS: The bone created through orthodontic tooth movement was stable in
      both the horizontal and vertical directions. Changes in the width of the alveolus
      were not related to the amount of bone at the place of agenesis at T1. When the
      canine erupts next to the central incisor, favorable conditions affect the
      formation of the bone mass through distalization of the canine at the site of the
      missing lateral incisor.

PMID- 21195275
TI  - In-vitro assessment of the forces generated by lingual fixed retainers.
AB  - INTRODUCTION: The aim of this article was to assess the effect of wire adaptation
      on the lingual surfaces of mandibular anterior teeth with 3 types of lingual
      retainers on the development of vertical and labiolingual forces. METHODS: Ten
      retainers (canine to canine) were constructed from each of the following wires:
      Wildcat 0.0195-in heat-treated 3-strand twist-flex wire (GAC, Bohemia, NY); Penta
      one 0.0215-in 6-strand as received; and Penta-one 0.0215-in 6-strand after heat
      treatment at 350 degrees C for 4 minutes (both, Masel Orthodontics, Carlsbad,
      Calif). The retainers were bonded on each tooth of an acrylic resin model, and
      the model was installed in the Orthodontic Measurement and Simulation System. The
      vertical and labiolingual forces generated were measured for wire displacements
      up to 0.2 mm in 0.02-mm increments. RESULTS: Wire displacement of 0.2 mm exerted
      forces as high as 1 N on the teeth. In the vertical direction, the highest force
      levels were recorded for the as-received Penta-one 0.0215-in and the lowest from
      its heat-treated counterpart. In the horizontal plane, the as-received Penta-one
      0.0215-in exerted the highest forces. CONCLUSIONS: The forces recorded from the
      lingual retainer wires during 0.2-mm simulated intrusion-extrusion and buccal
      lingual movements might generate high forces that exceed 1 N and be large enough
      to produce unwanted tooth movement during retention. The only significant
      determinant of the generated forces was the amount of wire displacement and not
      the type of wire used in this study.

PMID- 21195276
TI  - Incidence of open gingival embrasures after mandibular incisor extractions: a
      clinical photographic evaluation.
AB  - INTRODUCTION: The purposes of this study were to determine the incidence of open
      gingival embrasures after a single mandibular incisor extraction and to
      investigate whether age, sex, interproximal pretreatment and posttreatment
      contact location, or the type of mandibular incisor were predictors of the
      incidence and magnitude of open gingival embrasures. METHODS: Pretreatment and
      posttreatment intraoral frontal photos of 51 adults who had 1 mandibular incisor
      extracted were evaluated to determine the incidence and magnitude of open
      gingival embrasures. RESULTS: The incidence of open gingival embrasures was 68%;
      the embrasures were moderately noticeable to very noticeable in 52% of those
      patients. Age, sex, incisor type, and location of interproximal contact before
      treatment were not predictors of open gingival embrasures after mandibular
      incisor extractions. An interproximal contact in the incisal third at the end of
      treatment was associated with the formation of an open gingival embrasure.
      CONCLUSIONS: Open gingival embrasures are a common finding after the extraction
      of a mandibular incisor, and the magnitude of this embrasure is clinically
      noticeable.

PMID- 21195277
TI  - Nickel: periodontal status and blood parameters in allergic orthodontic patients.
AB  - INTRODUCTION: The aims of this study were to compare blood parameters and
      periodontal characteristics of orthodontic patients allergic to nickel with those
      of nonallergic patients and to determine the correlation between blood components
      and periodontal abnormalities. METHODS: Ninety-six randomly selected patients
      participated in the study. After determining the prevalence of those allergic to
      nickel, 2 groups were formed: 16 allergic patients and 16 nonallergic patients.
      Allergies to nickel were diagnosed by using the patch test, periodontal
      conditions were determined by using the gingival index, and humoral
      characteristics were determined through a complete blood test, including the
      quantification of nickel in the blood and the immunoglobulin E level. Feces
      examinations were performed to control for parasitic infections. Periodontal
      evaluations were performed blindly. Statistical analysis included the unpaired t
      test, the Mann-Whitney test, and the Pearson and Spearman correlations (P
      <=0.05). RESULTS: Statistically significant differences between groups were found
      for bands (P = 0.001). There was no correlation between the concentration of
      nickel and immunoglobulin E level (P = 0.674, experimental group; P = 0.605,
      control group). However, there was a positive correlation between the gingival
      index and the number of bands (P = 0.05). CONCLUSIONS: Nickel can have an
      influence over the periodontal status of allergic orthodontic patients, causing
      an increase in band quantification that was correlated to gingival index.

PMID- 21195278
TI  - Histologic evaluation of root response to intrusion in mandibular teeth in beagle
      dogs.
AB  - INTRODUCTION: The purpose of this article was to histologically evaluate root
      resorption and repair after orthodontic intrusion with different force magnitudes
      and fixed anchorage. METHODS: A randomized split-mouth repeated-measure design
      was used. Intrusive forces were applied for 98 days to the mandibular second,
      third, and fourth premolars of 8 mature beagle dogs. Two miniscrew implants were
      used as anchorage to apply constant intrusive forces of 50, 100, or 200 g per
      tooth. Demineralized sections of each tooth were stained and histologically
      studied for root resorption. Multilevel statistical procedures were used to
      evaluate the results. RESULTS: Root resorption was present in all teeth,
      independent of the force applied. Significant differences were found between root
      regions, with the apices and the interradicular regions the most affected and
      with dentin involvement at the furcation. There was cementum repair in 24.14% of
      the lacunae. Light constant intrusive forces between 50 and 200 g showed no
      significant differences in the amount of resorption produced. Resorption was more
      frequently seen at the level of the apices and the furcation. CONCLUSIONS:
      Orthodontically induced root resorption is not clinically significant after
      application of continuous intrusive forces between 50 and 200 g. Moreover, there
      is no relationship between root resorption, the position of posterior mandibular
      teeth in the arch, and the amount of intrusive force applied.

PMID- 21195279
TI  - Discrepancy index relative to age, sex, and the probability of completing
      treatment by one resident in a 2-year graduate orthodontics program.
AB  - INTRODUCTION: The American Board of Orthodontics' discrepancy index (DI) was
      designed to objectively quantify the complexity of a malocclusion before
      orthodontic treatment. In this study, we assessed the influence of age and sex on
      the DI distribution of a large mixed sample of patients. An additional objective
      was to ascertain the effectiveness of the DI for predicting the probability that
      1 resident can complete the treatment of the malocclusion in a 24-month
      residency. METHODS: A group of 6 calibrated investigators independently
      determined the DI scores for 716 consecutive patients in the permanent dentition
      from the patient pool of Indiana University's graduate orthodontics program over
      7 years. The DI was scored and compared with the patient's sex and age, and it
      was noted whether the patient was transferred to a second resident when the first
      one graduated. RESULTS: The DI is not significantly related to sex or age, but it
      was a significant predictor for patients who required transfer to a second
      resident for completion of treatment. CONCLUSIONS: The DI was a relatively stable
      index for measuring malocclusion complexity. It is independent of sex or age but
      is a consistent indicator of the greater time and effort required to complete
      treatment, because of the significant correlation to the necessity to transfer
      patient care to a second resident.

PMID- 21195280
TI  - Static frictional force and surface roughness of various bracket and wire
      combinations.
AB  - INTRODUCTION: During sliding mechanics, frictional resistance is an important
      counterforce to orthodontic tooth movement, which must be controlled to allow
      application of light, continuous forces. We investigated the static frictional
      resistance between 3 modern orthodontic brackets-ceramic with gold-palladium
      slot, ceramic, and stainless steel-and 4 archwires (0.019 * 0.025-in)-stainless
      steel, nickel-titanium, titanium-molybdenum alloy (TMA), and low-friction colored
      TMA. METHODS: All tests were carried out in a dry state on a universal testing
      machine. Surface topography of bracket slots and archwires was studied by using a
      scanning electron microscope and quantified by using a surface roughness testing
      machine (profilometer). RESULTS: In the scanning electron microscope
      measurements, the smoothest surface was the ceramic gold-palladium bracket and
      stainless steel wire. The profilometer quantified the surface roughness, which
      also was lowest for the ceramic gold-palladium bracket and stainless steel wire.
      The ceramic bracket with the gold-palladium slot showed the least frictional
      values in all combinations and could be a promising alternative to solve the
      problem of friction. Frictional values for colored TMA were comparable with
      stainless steel wires and might be a good alternative during space closure in
      sliding mechanics. CONCLUSIONS: Ceramic with gold-palladium slot bracket and
      colored TMA archwire seem to be a good alternative to stainless steel in space
      closure with sliding mechanics.

PMID- 21195281
TI  - Three-year follow-up of bimaxillary surgery to correct skeletal Class III
      malocclusion: stability and risk factors for relapse.
AB  - INTRODUCTION: The purpose of this study was to evaluate long-term skeletal and
      occlusal stability after bimaxillary surgery to correct skeletal Class III
      malocclusion. METHODS: The sample comprised 81 consecutively treated patients.
      All subjects had received a combined 1-piece LeFort I and bilateral sagittal
      split ostotomies with rigid fixation between 1990 and 2003 and were followed for
      3 years. Lateral cephalograms were obtained before surgery and at 5 occasions
      after surgery. RESULTS: The mean setback was 6.9 mm in the mandible, and the
      maxilla was moved forward 3.7 mm. In most patients, the posterior maxilla was
      impacted. Relapse of maxillary advancement was insignificant (0.1 mm), whereas
      relapse at B-point was on average 1.7 mm (P <0.010). After 3 years, mean overjet
      and overbite amounts were 2.0 and 1.9 mm, respectively. Skeletal relapse of the
      mandible increased significantly with the surgical setback (P <0.001) and the
      change in the vertical position of the posterior maxilla (P = 0.010)
      (multivariate regression analysis). CONCLUSIONS: Bimaxillary surgery resulted in
      good occlusal stability. Maxillary advancement was stable, whereas relapse of the
      mandibular setback varied. Risk factors for horizontal relapse of the mandible
      were large setback and inferior repositioning of the posterior maxilla.

PMID- 21195282
TI  - Dental health assessed after interproximal enamel reduction: caries risk in
      posterior teeth.
AB  - INTRODUCTION: We investigated whether careful interdental enamel reduction (using
      extrafine diamond disks with air cooling, followed by contouring with triangular
      diamond burs and polishing) leads to increased caries risk in premolars and first
      molars. METHODS: Our subjects were 43 consecutive patients from 19 to 71 years of
      age who had received mesiodistal enamel reduction of anterior and posterior teeth
      4 to 6 years previously. Dental caries were assessed on standardized bite-wing
      radiographs according to a 5-grade scale and with a fine-tip explorer catch. The
      incidence of interproximal caries was compared between reproximated and unground
      contralateral surfaces in the same patient. Patients were asked about their
      toothbrushing habits, use of dental floss and toothpicks, and regular fluoride
      supplementation after the orthodontic appliances were removed. RESULTS: The
      overall clinical impression generally showed healthy dentitions with excellent
      occlusion. Only 7 (2.5%) new caries lesions (all grade 1) were found among 278
      reproximated mesial or distal surfaces, in 3 patients. Among 84 contralateral
      unground reference tooth surfaces, 2 lesions (2.4%) were seen. On nonpaired
      premolars and molars that had not been ground, 23 surfaces had to be referred for
      caries treatment (grade 3 or occlusal caries). Eleven of these occurred in 1
      patient. None of the 43 patients reported increased sensitivity to temperature
      variations. CONCLUSIONS: Interdental enamel reduction with this protocol did not
      result in increased caries risk in posterior teeth. We found no evidence that
      proper mesiodistal enamel reduction within recognized limits and in appropriate
      situations will cause harm to the teeth and supporting structures.

PMID- 21195283
TI  - Maxillary protraction with miniplates providing skeletal anchorage in a growing
      Class III patient.
AB  - Maxillary protraction headgear has been used in the treatment of Class III
      malocclusion with maxillary deficiency. However, loss of dental anchorage has
      been reported with tooth-borne anchorage such as lingual arches and expansion
      devices. This side effect can be minimized with skeletal anchorage devices such
      as implants, onplants, mini-implants, and miniplates. The use of miniplates for
      maxillary protraction in the mixed dentition has not been reported in the
      literature. This case report describes the treatment of an 8-year-old girl with a
      Class III malocclusion and maxillary deficiency. Miniplates were used as skeletal
      anchorage for maxillary protraction followed by phase 2 orthodontic treatment
      with fixed appliances. Skeletal, dental, and facial changes in response to
      orthopedic and orthodontic treatment are reported to illustrate the esthetics,
      function, and stability of treatment with this new technique.

PMID- 21195284
TI  - Efficient usage of implant anchorage to treat overerupted maxillary first molar
      and mesially inclined mandibular molars.
AB  - This case report demonstrates the efficient use of implant anchorage in a patient
      with mesially inclined mandibular molars and an overerupted maxillary molar. A 14
      year-old girl had an overerupted maxillary right first molar, possibly because of
      severely inclined mandibular right molars. Two-step use of miniplate anchorage in
      the right zygomatic process was proposed. As the first step, the overerupted
      maxillary first molar was intruded with elastic chains from the miniplate for 10
      months. Then the maxillary right molars were distalized by using the miniplate to
      correct the Class II molar relationship. In the mandible, the first molar was
      extruded with intermaxillary elastics applied from the miniplate to the molar for
      7 months after the uprighting of the mandibular right second molar. The results
      suggest that the use of 2-step implant anchorage is efficient for intrusion and
      distalization of maxillary molars and extrusion and uprighting of mandibular
      inclined molars.

PMID- 21195285
TI  - Accidental ingestion of a fractured Twin-block appliance.
AB  - Orthodontic appliances that become dislodged can cause problems in the airway or
      the gastrointestinal tract. Accidental ingestion of an appliance during a chair
      side procedure or because of inadequate retention of the appliance can create a
      medical emergency with potentially serious complications, including death from
      aspiration of the foreign body. This article reports the accidental ingestion of
      a fractured Twin-block appliance. The ease with which removable appliances can
      become dislodged if retention is inadequate is discussed, and some serious
      complications that can arise are described. Precautions the orthodontist can take
      to prevent such accidents are presented.

PMID- 21195286
TI  - Comparison of mesiodistal root angulation with posttreatment panoramic
      radiographs and cone-beam computed tomography.
AB  - INTRODUCTION: Orthodontists assess mesiodistal root angulations before, during,
      and after orthodontic treatment as an aid in establishing proper root position.
      Panoramic imaging has been useful for this purpose and is a valuable screening
      tool in diagnosis and planning treatment of orthodontic patients. Cone-beam
      computed tomography (CBCT) for imaging of the craniofacial complex creates the
      opportunity to evaluate 3-dimensional images compared with traditional 2
      dimensional images. The purpose of this project was to compare mesiodistal root
      angulations by using posttreatment panoramic radiographic images and CBCT scans.
      METHODS: Mesiodistal root angulations from panoramic images and CBCT scans of 35
      orthognathic surgery patients after orthodontic treatment were compared. The
      panoramic images were measured by using VixWin (Gendex Dental Systems, Des
      Plaines, Ill), and the CBCT scans by using InvivoDental 3D (version 4.1,
      Anatomage, San Jose, Calif). The mesiodistal root angulation of each maxillary
      and mandibular tooth was measured by using the occlusal plane as the reference
      line. With an intercept-only linear regression for correlated data (with an
      unstructured covariance structure), the global test of whether the mean vector of
      all differences for the teeth is zero was performed separately for the 2 arches.
      RESULTS: The global test for both arches was statistically significant (P
      <0.001), indicating an overall difference in root angulation between measurements
      from panoramic and CBCT images. There was no discernible pattern in the average
      differences between panoramic and CBCT measurements. CONCLUSIONS: The assessment
      of mesiodistal tooth angulation with panoramic radiography should be approached
      with caution and reinforced by a thorough clinical examination of the dentition.

PMID- 21195287
TI  - Litigation and legislation: what do patients actually consent to?

PMID- 21195288
TI  - Common errors in preparing for and completing the American Board of Orthodontics
      clinical examination.

PMID- 21195289
TI  - Acupuncture attenuates autonomic responses to smoking-related visual cues.
AB  - OBJECTIVES: In smokers, smoking-associated cues produce smoking urges and
      cravings, which are accompanied by autonomic dysfunction in response to these
      cues. We investigated whether or not acupuncture ameliorated cigarette withdrawal
      symptoms, as well as attenuated the autonomic responses to smoking-related visual
      cues in smokers using a power spectrum analysis of heart rate variability (HRV).
      INTERVENTIONS: Fifteen subjects were treated with real acupuncture (RA) at HT7
      and 14 subjects received sham acupuncture (SA) at LI10 using the Park Sham
      Device. MAIN OUTCOME MEASURE: The cigarette withdrawal scale (CWS) was measured
      on the third day after the subjects had quit smoking. We compared the low
      frequency/high-frequency (HF/LF) ratio in the HRV of the RA and SA groups during
      a distraction task using neutral and smoking visual cues. RESULTS: The CWS of the
      RA group was significantly lower than that of the SA group. The increase in the
      LF/HF ratio of HRV induced by the smoking-related visual cues was also
      significantly lower in the RA group when compared with the SA group. Acupuncture
      not only ameliorated cigarette withdrawal, but also weakened the autonomic
      responses to smoking cues during withdrawal. CONCLUSIONS: These findings suggest
      that acupuncture might help in smoking cessation by attenuating withdrawal
      symptoms and smoking cues-induced autonomic responses.

PMID- 21195290
TI  - Effects of Sanyinjiao (SP6) with electroacupuncture on labour pain in women
      during labour.
AB  - OBJECTIVE: To evaluate the effects of Sanyinjiao (SP6) with electroacupuncture on
      labour pain in women during the labour process. METHODS: A total of 350 women in
      labour from three centres were randomly divided into the electroacupuncture group
      (acupuncture group), the sham electroacupuncture group (sham group) and the
      control group. Women in labour in the electroacupuncture group received the
      electroacupuncture on the point Sanyinjiao (SP6). The analgesic effect was self
      rated by women in labour, using visual analogue scale (VAS). The duration and
      paralysis time of uterine contraction, uterine contraction regularity, degree of
      cervical extension, presentation of foetal descent, the condition of intra-partum
      haemorrhage and postpartum haemorrhage, labour manner, lochia, involution of
      uterus, milk secretion, neonate Apgar Score and neonate body height and weight
      were also measured. All data were analysed with Statistical Package for Social
      Sciences (SPSS) 12.0. RESULTS: Labour pain scores from women in the acupuncture
      group were less than in the control group at needle retaining at 30min, 2 and 4h
      after needle withdrawal. Other evaluated indices did not show significant
      differences among the three groups. No adverse events were observed during the
      labour process. CONCLUSION: SP6 with electroacupuncture could be an effective way
      for decreasing labour pain.

PMID- 21195291
TI  - Carthami-Semen acupuncture point injection for chronic daily headache: a pilot,
      randomised, double-blind, controlled trial.
AB  - OBJECTIVES: This study was conducted to examine the possibility of Carthami-Semen
      (CS, Safflower seed) acupuncture point injection as a new promising treatment for
      chronic daily headache (CDH). METHODS: A total of 40 subjects with CDH were
      recruited and randomised to a CS acupuncture point injection group or a normal
      saline (NS) acupuncture point injection group. Acupuncture point injections were
      applied twice a week during 4 weeks to the bilateral Fengchi (GB20), Jianjing
      (GB21) and Taiyang (EX-HN5) acupoints with CS extract or NS. OUTCOME MEASURES:
      The primary outcome measure was headache-related quality of life (QoL), assessed
      using the Headache Impact Test (HIT). Secondary outcome measures were the changes
      in the number of headache-free days and health status as assessed with the Short
      Form (36) Health Survey (SF-36). RESULTS: HIT scores decreased by 14.9 points in
      the CS acupuncture point injection group compared with 7.9 points in the NS
      acupuncture point injection group (p=0.013). Headache-free days increased by
      32.6% in the CS acupuncture point injection group compared with 17.4% in the NS
      acupuncture point injection group (p=0.045). There were significant increases in
      SF-36 scores compared with baseline in both groups, but the mean improvement was
      greater in the CS acupuncture point injection group. No serious adverse events
      (AEs) were reported. CONCLUSIONS: We suggest that the CS acupuncture point
      injection could be a new safe and promising treatment for CDH. A larger and long
      term follow-up trial is needed to determine more definitely the efficacy of CS
      acupuncture point injection and to elucidate how long the effect lasts.

PMID- 21195292
TI  - Assessment of a traditional acupuncture therapy for chronic neck pain: a pilot
      randomised controlled study.
AB  - OBJECTIVE: This study is aimed to assess the efficacy of traditional acupuncture
      for chronic neck pain in patients by comparing the differences in symptoms,
      dysfunctions and quality of life. METHODS: The study used a two-arm, single
      blinded, randomised controlled design. The patients were randomised to the study
      group and control group, who respectively received traditional acupuncture and
      placebo treatment. The Northwick Park Neck Pain Questionnaire (NPQ), visual
      analogue scale (VAS), Short Form (36) Health Survey (SF-36) and doctor's
      judgement were applied for measuring effectiveness. The patients' effectiveness
      outcome was assessed, respectively, before the intervention, immediately after
      the intervention, at the end of the first month of follow-up and at the end of
      the third month of follow-up. The statistical analysis was done on Statistical
      Package for Social Sciences (SPSS) v13, which included comparison of demographic
      and clinical homogeneity, the repeated measures approach based on the general
      linear model (GLM) for effectiveness assessment and the sum rank test for
      doctors' subjective efficacy judgement. RESULTS: Totally, 190 patients were
      recruited and 178 patients (88 in the study group and 90 in the control group)
      completed the intervention and follow-up assessment. The scores of NPQ, VAS and
      SF-36 were improved after the intervention and during follow-up (P<0.01 vs.
      before the intervention). The patients in the study group had better
      effectiveness outcome in NPQ, VAS and in the VT, SF and MH domains of SF-36
      (P<0.05). CONCLUSION: Traditional acupuncture can relieve pain intensity and
      improve the quality of daily life with a relative long-term clinical efficacy in
      patients with chronic neck pain.

PMID- 21195293
TI  - Sympathomodulatory effects of Saam acupuncture on heart rate variability in night
      shift-working nurses.
AB  - OBJECTIVE: We assessed the effects of Saam (traditional Korean) acupuncture on
      the autonomic nervous system in night-shift nurses using power-spectral heart
      rate variability (HRV) analysis. METHODS: This study had a 2 * 4 cross-over
      design with a series of six (n = 1) controlled trials. Six night-shift nurses
      were randomly divided into two groups, and each nurse received four acupuncture
      treatments on the third day of night-shift work. One group started with Saam
      acupuncture (gallbladder jeonggyeok), while the other started with sham
      acupuncture. Saam acupuncture and sham acupuncture were applied in turn. HRV was
      measured before and after treatment. For statistical analysis, the results of the
      two groups were combined, and a Bayesian model was used to compare the changes in
      HRV values before and after treatment, between Saam and sham acupuncture.
      RESULTS: As the ratio of low- to high-frequency power (LF/HF) for HRV increased
      on the third day of night-shift work in the pilot study, HRV measurements were
      made on the third day. Compared with sham acupuncture, Saam acupuncture reduced
      sympathetic activity; the overall median treatment effect estimate in LF
      normalised units decreased by -17.4 (confidence interval (CI): -26.67, -8.725)
      and that for LF/HF decreased by -1.691 (CI: -3.222, -0.3789). The overall median
      treatment effect estimate in HF normalised units increased by 17.41 (CI: 6.393,
      27.13) with Saam acupuncture, suggesting an increase in parasympathetic activity.
      CONCLUSION: Saam acupuncture may attenuate the imbalance between sympathetic and
      parasympathetic activities induced by night-shift work in nurses.

PMID- 21195294
TI  - Non-penetrating sham needle, is it an adequate sham control in acupuncture
      research?
AB  - OBJECTIVES: This study aimed to determine whether a non-penetrating sham needle
      can serve as an adequate sham control. DESIGN: We conducted a randomised, subject
      blind, sham-controlled trial in both acupuncture-naive and experienced healthy
      volunteers. SETTING AND INTERVENTIONS: Participants were randomly allocated to
      receive either real acupuncture (n=39) or non-penetrating sham acupuncture (n=40)
      on the hand (LI4), abdomen (CV12) and leg (ST36). The procedures were
      standardised and identical for both groups. MAIN OUTCOME MEASURES: Participants
      rated acupuncture sensations on a 10-point scale. A blinding index was calculated
      based on the participants' guesses on the type of acupuncture they had received
      (real, sham or do not know) for each acupuncture point. The association of
      knowledge about and experience in acupuncture with correct guessing was also
      examined. RESULTS: The subjects in both groups were similar with respect to age,
      gender, experience or knowledge about acupuncture. The sham needle tended to
      produce less penetration, pain and soreness only at LI4. Blinding appeared to be
      successfully achieved for ST36. Although 41% of participants in the real
      acupuncture group made correct guesses for LI4, 31% guessed incorrectly for CV12,
      beyond chance level. People with more experience and knowledge about acupuncture
      were more likely to correctly guess the type of needle they received at ST36
      only, compared to that at the other points. CONCLUSIONS: A non-penetrating sham
      needle may successfully blind participants and thus, may be a credible sham
      control. However, the small sample size, the different needle sensations, and the
      degree and direction of unblinding across acupuncture points warrant further
      studies in Korea as well as other countries to confirm our finding. Our results
      also justify the incorporation of formal testing of the use of sham controls in
      clinical trials of acupuncture.

PMID- 21195295
TI  - An fMRI study of acupuncture-induced brain activation of aphasia stroke patients.
AB  - This investigation aims to test the effect of acupuncture on word generation
      activation (WGA) in post-stroke aphasia patients. Seven vascular aphasia patients
      and 14 control subjects were studied using functional magnetic resonance imaging
      (fMRI). Each performed: (1) a word generation (WG) task alone, followed by (2)
      repeating WG after insertion of acupuncture needles (WGN) into SJ 8 (a language
      implicated acupoint), followed by (3) repeating WGN reinforced by electrical
      stimulation (WGA) of SJ 8, and finally (4) electrical stimulation (ES) of SJ 8
      alone. Significant activation was found in the opercular, triangular, or insula
      during the ES stimulation in patients when comparing each patient to 14 normal
      controls. For the WG task, significant activation was found in the inferior
      frontal gyrus when comparing each patient to 14 normal controls. The signal
      induced by acupuncture was larger than that of the WG task in the left middle
      frontal gyrus with the comparison of WGA vs. WGN in seven patients. Further, main
      significant effects in the right insula in patients were observed when comparing
      seven patients to 14 normal controls. The activation induced by ES stimulation
      was only found on the left side in controls. This activation was observed on the
      lesion side of superior and middle frontal gyrus (SMFG) in patients. This study
      demonstrates for the first time that language-deficit-implicated acupoint
      stimulation can selectively activate the brain on the lesion side in post-stroke
      aphasia patients. These results suggest that acupuncture may have therapeutic
      benefits in post-stroke aphasia patients.

PMID- 21195296
TI  - Comparison of biomechanical properties between acupuncture and non-penetrating
      sham needle.
AB  - OBJECTIVES: A non-penetrating sham needle has been considered as a reliable
      control treatment in the field of acupuncture research. However, some concerns
      with regard to the credibility of sham needles have also been raised. We
      investigated whether there were differences in biomechanical properties and
      acupuncture sensation ratings in the process of needling between verum
      acupuncture (VA) and sham acupuncture (SA). METHODS: To quantify biomechanical
      force during needling in a cross-over design, we used a computer-controlled
      needling system. Fourteen participants received VA or SA at acupuncture point
      LI4, with no visual impact. They were asked to complete an acupuncture sensation
      form, including penetration, acute pain and DeQi sensations, and to identify the
      needling type they received. RESULTS: We found that there was a significant
      difference in insertion force between VA and SA (68.5 +/- 12.2 vs. 27.2 +/- 3.9
      gf; p < 0.001). Participants clearly distinguished between the two kinds of
      stimulation and rated higher sensory ratings in the VA session (penetration
      sensation: 4.9 +/- 3.1 vs. 1.7 +/- 2.3, acute pain: 4.9 +/- 2.7 vs. 1.9 +/- 2.6,
      respectively; p < 0.01). CONCLUSIONS: Our findings demonstrate that differential
      biomechanical forces such as insertion and pullout force contribute to the
      sensation of real and non-penetrating sham needles.

PMID- 21195297
TI  - Translational research efforts in biomarkers and biology of early transplant
      related complications.
AB  - In the time since the first allogeneic hematopoietic stem cell transplantation
      (HSCT) was performed over 40 years ago, this life-saving procedure has been used
      increasingly for patients with hematologic, metabolic, and malignant diseases.
      Despite major advances in our understanding of the immunologic processes (both
      beneficial and injurious) that are associated with HSCT and improvements in
      supportive and critical care medicine, successful outcomes are still limited by
      several serious complications. As such, the establishment of effective
      therapeutic strategies for these complications will be crucial as increasing
      numbers of high-risk transplants are performed each year. The development of such
      approaches is fundamentally dependent upon a basic understanding of
      pathophysiologic mechanisms of disease and also on our ability to successfully
      translate these insights back to the bedside. This brief review will highlight
      breakthroughs in translational research endeavors that have paved the way for the
      development of novel strategies intended to change the standard of care and
      optimize outcomes for patients in whom allogeneic HSCT offers the only hope for a
      cure.

PMID- 21195298
TI  - Cellular therapy for fanconi anemia: the past, present, and future.
AB  - Allogeneic hematopoietic cell transplantation (HCT) remains the only proven
      curative therapy for the hematologic manifestation of Fanconi anemia (FA). Over
      the past 2 decades, major advances have been made such that transplant outcomes
      have markedly improved. With the development of in vitro fertilization and
      preimplantation genetic diagnosis, HLA-matched sibling donor umbilical blood
      transplantation may be an option for more patients with FA. Recently, the use of
      pluripotent stem cells has been explored as a novel approach to model the
      hematopoietic developmental defects in FA, and to provide a potential source of
      autologous stem cells that can be genetically manipulated and used to generate
      corrected hematopoietic progenitors.

PMID- 21195299
TI  - An update on the molecular pathogenesis of myelodysplastic syndromes.

PMID- 21195300
TI  - Controversies in the treatment of CML in children and adolescents: TKIs versus
      BMT?
AB  - Chronic myeloid leukemia (CML) is a relatively rare hematopoietic malignancy in
      the pediatric and adolescent population. This makes it difficult to perform
      clinic trials that can define the best therapeutic option when considering the
      impact of tyrosine kinase inhibitors (TKIs) versus the established approach of
      allogeneic hematopoietic cell transplantation (HCT). With the relatively low
      toxicity of TKIs, there are little data regarding when HCT or long-term TKI
      therapy is a better option. There are even less data regarding the duration of
      TKI treatment in the pediatric CML in chronic phase (CML-CP) patients who may
      receive over 60 years of therapy. As children and adolescent are treated for
      longer times with TKIs, it has become clear that toxicities may make long-term
      TKI therapy less attractive compared to allogeneic HCT. HCT has the long-term
      complications of growth failure, infertility, chronic graft-versus-host disease
      (GVHD), metabolic syndrome, and secondary malignancies, whereas prolonged TKIs
      may cause growth failure, hepatic, and cardiac complications. Moreover, HCT is a
      potentially curative intervention, whereas TKI is not curative, requiring
      prolonged exposure. In this article, we discuss the relative merit of the 2
      therapeutic approaches and recommend that all children and adolescents with CML
      CP should initially be treated with imatinib and maintained with TKI therapy
      indefinitely if there is a good response. We recommend that allogeneic HCT with
      an HLA-identical sibling donor or closely matched unrelated donor be considered
      for patients with treatment failure or recurrence after receiving salvage second
      generation TKI treatment. We also conclude that randomized international trials
      are urgently needed to evaluate the best therapies for pediatric CML.

PMID- 21195301
TI  - Chronic granulomatous disease: lessons from a rare disorder.
AB  - Chronic granulomatous disease (CGD) is a rare primary immunodeficiency with X
      linked or autosomal recessive inheritance involving defects in genes encoding
      phox proteins, which are the subunits of the phagocyte NADPH oxidase. This
      results in failure to produce superoxide anion and downstream antimicrobial
      oxidant metabolites and to activate antimicrobial proteases. Affected patients
      are susceptible to severe, life-threatening bacterial and fungal infections and
      excessive inflammation characterized by granulomatous enteritis resembling
      Crohn's disease and genitourinary obstruction. Early diagnosis of CGD and rapid
      treatment of infections are critical. Prophylaxis with antibacterial and mold
      active antifungal agents and the administration of interferon-gamma has
      significantly improved the natural history of CGD. Currently, the only cure is
      allogeneic hematopoietic cell transplant (HCT), although there remains
      controversy as to which patients with CGD should get a transplant. Allele-based
      HLA typing of alternative donors, improved supportive care measures, and use of
      reduced toxicity conditioning have resulted in event-free survival (EFS) of at
      least 80% even with an unrelated donor and even better when the patient has no
      active infections/inflammation. Gene correction of CGD would eliminate the risks
      of graft-versus-host disease (GVHD) and the immunoablative chemotherapy required
      for allogeneic HCT. Based on gene therapy trials in patients with SCID-X1, ADA
      SCID, and the early experience with CGD, it is clear that at least some degree of
      myeloablation will be necessary for CGD as there is no inherent selective growth
      advantage for gene-corrected cells. Current efforts for gene therapy focus on use
      of lentivector constructs, which are thought to be safer from the standpoint of
      insertional mutagenesis and more efficient in transducing hematopoietic stem
      cells (HSCs).

PMID- 21195302
TI  - Ethical considerations in pediatric BMT donors and recipients.

PMID- 21195303
TI  - High-risk pediatric acute lymphoblastic leukemia: to transplant or not to
      transplant?
AB  - Because survival with both chemotherapy and allogeneic hematopoietic stem cell
      transplantation (HSCT) approaches to high-risk pediatric acute lymphoblastic
      leukemia (ALL) generally improves through the years, regular comparisons of
      outcomes with either approach for a given indication are needed to decide when
      HSCT is indicated. Improvements in risk classification are allowing clinicians to
      identify patients at high risk for relapse early in their course of therapy.
      Whether patients defined as high risk by new methods will benefit from HSCT
      requires careful testing. Standardization and improvement of transplant
      approaches has led to equivalent survival outcomes with matched sibling and well
      matched unrelated donors; however, survival using mismatched and haploidentical
      donors is generally worse. Trials comparing chemotherapy and HSCT must obtain
      sufficient data about therapy and stratify the analysis to assess the outcomes of
      best-chemotherapy with best-HSCT approaches.

PMID- 21195304
TI  - Genetic modification of T cells.
AB  - Adoptively transferred T cells have shown activity in treating viral infections
      after hemopoietic transplantation and anti-tumor activity against some
      malignancies such as melanoma and lymphoma. Current research focuses on defining
      the optimum type of cell for transfer to improve persistence and genetically
      modifying infused T cells to augment function, overcome tumor evasion strategies
      and allow ablation should adverse effects occur.

PMID- 21195305
TI  - Viral infections in immunocompromised patients.

PMID- 21195306
TI  - MSCs in hematopoietic cell transplantation.

PMID- 21195307
TI  - What did we learn in 2010 from the phase III trials? Is maintenance therapy the
      new standard for myeloma?

PMID- 21195308
TI  - Graft versus leukemia reactivity after allogeneic stem cell transplantation.

PMID- 21195309
TI  - Cord blood unit access and selection: 2010 and beyond: best practices and
      emerging trends in cord blood unit selection.
AB  - One-fifth, more than 1000, of all transplants facilitated in 2010 by the National
      Marrow Donor Program (NMDP) have employed 1 or 2 umbilical cord blood units as
      the graft source. As the use of umbilical cord blood for unrelated allogeneic
      hematopoietic cell transplantation increases, several issues emerge that require
      additional attention and refinement. The U.S. Food and Drug Administration is now
      far along in its implementation of regulatory controls for umbilical cord blood.
      After October 20, 2011, every unrelated-donor cord blood unit transplanted in the
      United States must be either licensed or covered under an FDA-accepted IND. It is
      incumbent upon transplant physicians to review and understand the implications of
      the FDA's new regulations. In addition, as more transplant programs adopt
      umbilical cord blood for transplantation, it is important to stay current with
      the best practices surrounding identification and selection of the best available
      units. Cell dose, HLA matching, location of mismatched loci, and the role of
      noninherited maternal alleles are all important considerations for unit
      selection. This complexity in selection of appropriate units raises issues about
      the desired inventory of umbilical cord blood units. How many units are needed to
      meet the needs of all patients who might benefit from cord blood transplantation?
      Newly developed simulation models are being utilized by NMDP to answer this
      question.

PMID- 21195310
TI  - From trees to the forest: genes to genomics.
AB  - Crick, Watson, and colleagues revealed the genetic code in 1953, and since that
      time, remarkable progress has been made in understanding what makes each of us
      who we are. Identification of single genes important in disease, and the
      development of a mechanistic understanding of genetic elements that regulate gene
      function, have cast light on the pathophysiology of many heritable and acquired
      disorders. In 1990, the human genome project commenced, with the goal of
      sequencing the entire human genome, and a "first draft" was published with
      astonishing speed in 2001. The first draft, although an extraordinary
      achievement, reported essentially an imaginary haploid mix of alleles rather than
      a true diploid genome. In the years since 2001, technology has further improved,
      and efforts have been focused on filling in the gaps in the initial genome and
      starting the huge task of looking at normal variation in the human genome. This
      work is the beginning of understanding human genetics in the context of the
      structure of the genome as a complete entity, and as more than simply the sum of
      a series of genes. We present 3 studies in this review that apply genomic
      approaches to leukemia and to transplantation to improve and extend therapies.

PMID- 21195311
TI  - Natural and expanded CD4(+)CD25(+) regulatory T cells in bone marrow
      transplantation.

PMID- 21195312
TI  - Hematopoietic stem cell transplantation for treatment of myleodysplastic
      syndromes.
AB  - Allogeneic stem cell transplantation is a potentially curative treatment for
      myelodysplastic syndromes. Transplants are clearly indicated in patients with
      intermediate-2 and high risk disease; there is controversy regarding when
      transplantation should be performed in patients with low and intermediate-1 risk
      disease. Most patients with MDS are over age 65 and Medicare has recently
      provisionally approved transplants, but only when performed as part of a
      comparative clinical trial which still must be finalized. Nonmyeloablative
      preparative regimens allow treatment of older patients with MDS, and novel
      approaches are under evaluation to reduce the risk of relapse and treatment
      related morbidity and mortality.

PMID- 21195314
TI  - Transplants for the old but not for the young?--The enigma of adult ALL.

PMID- 21195313
TI  - Stem cell transplantation for indolent lymphoma and chronic lymphocytic leukemia.
AB  - The indolent lymphomas, including chronic lymphocytic leukemia/small lymphocytic
      lymphoma (CLL) remain incurable with standard therapy. Autologous hematopoietic
      stem cell transplantation (HSCT) is feasible and has low treatment-related
      mortality in follicular lymphoma, but there are questions relating to optimal
      timing of the procedure, conditioning regimen, and late effects. Myeloablative
      allogeneic HSCT is associated with high treatment-related morbidity and
      mortality, few late relapses, but is applicable to only a small number of
      patients. The major focus of HSCT in these lymphomas has been with reduced
      intensity conditioning (RIC) allogeneic HSCT, which is applicable to the age
      distribution of these diseases and which exploits the graft-versus-lymphoma
      effect in these diseases. Steps to further decrease the morbidity and mortality
      of the RIC HSCT and in particular to reduce the incidence of chronic extensive
      graft-versus-host disease (GVHD) while maintaining tumor control remain the major
      focus. Many potential treatments are available for indolent lymphomas and CLL,
      and appropriate patient selection and the timing of HSCT remain controversial.
      The use of HSCT must always be weighed against the risk of the underlying
      disease, particularly in a setting where improvements in treatment are leading to
      improved outcome.

PMID- 21195316
TI  - Philadelphia-positive acute lymphoblastic leukemia--is bone marrow transplant
      still necessary?

PMID- 21195315
TI  - Interpreting data on transplant selection and outcome in adult acute
      lymphoblastic leukemia (ALL).
AB  - Until 10 to 15 years ago allogeneic transplants were performed in acute
      lymphoblastic leukemkia (ALL) mostly for advanced disease. They were rarely
      performed in first remission except for patients who were positive for the
      Philadelphia chromosome. Over the past decade, allogeneic transplants are being
      increasingly performed also for select patients in first remission, and the use
      of matched unrelated donors has vastly increased the availability of the donor
      pool for ALL patients. The data for reduced-intensity conditioning (RIC)
      transplants are at their infancy for ALL, but are likely to come into their own
      over the next decade, given the vast potential of offering this also to older
      patients or those with comorbidities. Despite the plethora of data, reports from
      various study groups differ in their enthusiasm for transplantation in many
      instances, and published data are often contradictory. Much of the data may have
      inherent selection biases and their interpretation may be confusing and
      difficult. The study conditions should be carefully described for physicians and
      patients to be able to adequately interpret the data.

PMID- 21195317
TI  - Point-counterpoint: haploidentical family donors versus cord blood
      transplantation.

PMID- 21195318
TI  - Nontransplantation options for patients with myelodysplastic syndromes.

PMID- 21195319
TI  - US cancer care: should insurers really be in the driving seat?

PMID- 21195320
TI  - EPCAM deletions, Lynch syndrome, and cancer risk.

PMID- 21195321
TI  - Should anthracyclines and dexrazoxane be used for children with cancer?

PMID- 21195322
TI  - The challenges of surgical professionalism.

PMID- 21195323
TI  - Risk-adjusted scoring systems can predict surgeons' performance in colorectal
      surgery.
AB  - INTRODUCTION: the physiological & Operative Severity Score for the enUmeration of
      Mortality and Morbidity (POSSUM) was derived from a heterogeneous general
      population and has been used successfully as an audit tool to provide risk
      adjusted operative mortality rate. The aim of this study was to investigate
      whether risk-adjusted scoring systems can accurately predict outcomes of
      colorectal operations done by colorectal and non-colorectal surgeons. METHOD: the
      study was conducted prospectively on 899 consecutive patients who underwent major
      elective and emergency colorectal procedures over three years between 2002 and
      2004 at University Hospital Coventry and Warwickshire. The outcome parameter was
      defined as 30-day mortality. The observed mortality was then compared to POSSUM
      predicted mortality. Hosmer-Lemeshow and Fisher's Exact test were used to assess
      statistical significance in outcome between non- and coloproctologists. RESULTS:
      CR-POSSUM was the most accurate predictive model for outcomes of major colorectal
      operations between surgeons. The overall mortality rate amongst coloproctologists
      was 7% (5% elective & 13% emergency), whereas the overall mortality was 17% (3%
      elective & 21% emergency) in non-coloproctologists. CONCLUSION: CR-POSSUM was the
      better prediction model than POSSUM. Coloproctologists delivered a significantly
      lower overall mortality, but not in the emergency setting. However, given the few
      number of elective colorectal resections performed by non-coloproctologists, more
      cases are required to permit meaningful comparison for the outcomes of major
      colorectal operations among different surgeons.

PMID- 21195324
TI  - Routine pre-operative cross-match for elective colorectal resections: an
      appropriate use of resources?
AB  - INTRODUCTION: our Maximum Surgical Blood Ordering Schedule (MSBOS) recommends
      that blood is cross-matched prior to elective colorectal resections. National
      guidelines state that blood should not be cross-matched if blood usage is below
      50%. Our aims were to determine compliance with local and national guidelines and
      assess timing of blood transfusions. PATIENTS AND METHODS: consecutive elective
      colorectal resections from August 2007 to December 2008 were identified
      retrospectively using an electronic theatre management system. Patients
      transfused pre-operatively were excluded. Pre-operative cross-match status and
      blood transfusion data for each patient were identified using an electronic
      pathology system and case notes. Cross-match to transfusion (C:T) ratio and blood
      usage were calculated. RESULTS: one hundred and thirty one patients were
      identified. One hundred and sixteen patients (88.5%) had a pre-operative cross
      match, 13 patients (9.9%) had a pre-operative group and save and 2 patients
      (1.5%) had neither a valid cross-match nor group and save. A total of 295 units
      of blood were cross-matched; 79 units were transfused. Overall C:T ratio was
      3.7:1 and blood usage was 26.8%. Twenty eight patients (21.4%) were transfused
      within 5 days of surgery. Six patients (4.6%) were transfused intra-operatively;
      3 (2.3%) post-operatively on the same day; 8 (6.1%) on day one and 11 (8.4%) on
      or after day 2. CONCLUSION: we are over-ordering blood for elective colorectal
      resections and cannot justify performing a routine pre-operative cross-match.
      Blood should be grouped and saved pre-operatively and cross-matched only when
      clinically indicated to minimise inappropriate requests, expenditure and help
      improve blood stock management.

PMID- 21195325
TI  - The effect of surgeon volume on the need for transfusion following primary
      unilateral hip and knee arthroplasty.
AB  - INTRODUCTION: we reviewed transfusion practice following primary hip and knee
      arthroplasty with emphasis on the relationship between surgeon volume and the
      need for transfusion. MATERIALS/METHODS: review of a consecutive series of 508
      primary, elective, unilateral arthroplasties (248 THR/260 TKR) performed over a
      12-month period. Data were analysed to determine the overall rate of transfusion
      and the details of any such transfusion. Secondarily, multivariate regression was
      performed to determine the effects of surgeon volume and other recorded variables
      upon the need for transfusion. For the purpose of analysis we classified surgeons
      doing more than 52 arthroplasties a year as "high volume" and surgeons performing
      less than this number as "low volume". RESULTS: transfusion rates were 10% and 7%
      following THR and TKR. Multivariate analysis demonstrated that surgeon volume
      (<52 operations/yr vs. >52 operations/yr) and preoperative Hb<12g/dl were the
      only significant determinants of a need for postoperative transfusion (p<0.01).
      High volume and low volume surgeons transfused 5% vs. 17%, respectively (RR=3.3
      (95%CI 1.5-9.1) p=0.003) following THR and 4% vs. 13% (RR=3.6 (95%CI 1.4-9.3)
      p=0.006) following TKR. DISCUSSION AND CONCLUSION: High volume surgeons have
      significantly lower transfusion rates when compared to nationally accepted
      figures.

PMID- 21195326
TI  - Does bariatric surgery prior to lower limb joint replacement reduce
      complications?
AB  - Obesity is an increasing health concern in developed world. Bariatric surgery is
      considered in super-obese patients. Many of these patients will also require
      lower limb arthroplasty. This study was performed to investigate the
      complications of hip and knee replacement in patients who had bariatric surgery
      either before or after their joint replacement. Hospital episode statistics data
      for English NHS patients undergoing lower limb arthroplasty and bariatric surgery
      between 2005 and 2009 were analysed. The joint replacement-specific and general
      medical complications were compared between those undergoing joint replacement
      prior to bariatric surgery and vice versa, and also with the general English
      arthroplasty patient. One hundred and forty-three patients underwent bariatric
      surgery and joint replacement. Bariatric surgery was performed first in 53 and
      arthroplasty first in 90 patients. The mean age of obese patients was 9 years
      younger than the general arthroplasty population. Mean in-hospital stay was
      similar but general medical complications in obese patients appear to be less,
      possibly because of the lower age at the time of the procedure. Hip dislocation
      rate at 18 months was higher. Within the two obese groups wound infection rate
      was 3.5 times lower and readmission to hospital at 30 days appeared to be 7-times
      lower in patients who had bariatric surgery prior to joint replacement (p =
      0.06). In this patient group, the risk of complications following joint
      replacement appears to be lower if bariatric surgery is performed first.

PMID- 21195327
TI  - Cortical mastoidectomy in surgery of tubotympanic disease. Are we overdoing it?
AB  - BACKGROUND AND PURPOSE OF THE STUDY: the role of cortical mastoidectomy in the
      surgical treatment of tubotympanic type of otitis media has remained
      controversial especially when there is no evidence of active infection. Though
      literature is replete with studies for and against the requirement of
      mastoidectomy, there is a paucity of prospective studies in this regard. A
      randomized controlled trial was conducted to assess the impact of mastoidectomy
      in the management of mucosal chronic otitis media. METHODS: 62 patients with
      uncomplicated mucosal chronic otitis media were randomly allotted to two groups
      of 31 each. Patients in group A underwent tympanoplasty with mastoidectomy and
      group B underwent tympanoplasty without mastoidectomy. All the patients were
      followed up for a minimum of three months and results were assessed in terms of
      graft uptake, hearing improvement and need for repeat procedure. RESULTS: no
      significant difference in outcome was observed between the two groups in all
      parameters compared. The residual air-bone gap was 12.55 +/- 12.98 in group A and
      12.71 +/- 11.54 in group B. Graft uptake rate was 93.55% in group A and 96.775%
      in group B. 2 patients in group A and one patient in group B underwent repeat
      procedures. CONCLUSIONS: there is little evidence in favour of cortical
      mastoidectomy in surgery of tubotympanic disease.

PMID- 21195328
TI  - Treatment and outcomes of anorectal melanoma.
AB  - INTRODUCTION: anorectal melanoma is an uncommon disease constituting less than 3%
      of all melanomas. Due to its rarity, there are a lack of randomized control
      trials regarding appropriate management and current evidence is based mainly on
      retrospective studies. METHODS: in view of the controversial surgical treatment
      of anorectal melanoma, we review the most published literature in an attempt to
      elucidate its typical clinical features along with current thinking with respect
      to management approaches to this aggressive disease. Using the keywords
      "anorectal" and "malignant melanoma", a medline search of all articles in English
      was performed and the relevant articles procured. Additional references were
      retrieved by cross reference from key articles. RESULTS: anorectal melanoma
      affects the elderly with a slight preponderance for females. It commonly presents
      disguised as benign disease with local bleeding or suspicion for haemorrhoidal
      disease. There is no convincing evidence to indicate that radical resection of
      primary anorectal melanoma is associated with improvement in local control or
      survival, and local excision is an acceptable treatment option. CONCLUSION:
      optimum management depends on several factors and the therapeutic goals should be
      to lengthen survival and preserve quality-of-life. Given that wide local excision
      is a more limited intervention with comparable survival it should be considered
      as the initial treatment choice. Unfortunately prognosis for patients with this
      disease remains poor despite choice of treatment strategy with overall five year
      disease-free survival less than twenty percent in most studies.

PMID- 21195329
TI  - The role of microwave ablation in the management of hepatic colorectal
      metastases.
AB  - BACKGROUND: colorectal metastatic disease of the liver carries a significant
      mortality. Surgical resection improves prognosis in suitable patients. Microwave
      ablation is a recent innovative technique for the management of hepatic cancer.
      The aim of this study was to review the relevant literature regarding its safety
      and efficacy. METHODS: a literature search was performed using Pubmed, Athens,
      Medline and Google Scholar search engine. The following key words were used -
      thermal ablation, microwave ablation, liver, colorectal cancer, colorectal liver
      metastases - singly or in combination. To ensure an up-to-date literature search,
      the search has been restricted to the last ten years from 2000 to date
      inclusively, and the search was restricted to English language articles. To
      maximize this search backward chaining of reference lists from retrieved papers
      was also undertaken. CONCLUSIONS: microwave ablation adds another potential
      treatment modality to the hepatic surgeon armament. It can be performed safely
      and has an acceptably low complication rate.

PMID- 21195330
TI  - Surgery induced immunosuppression.
AB  - Surgery and anaesthesia result in a variety of metabolic and endocrine responses,
      which result in a generalised state of immunosuppression in the immediate post
      operative period. Surgery induced immunosuppression has been implicated in the
      development of post-operative septic complications and tumour metastasis
      formation. In addition the effectiveness of many treatments in the adjuvant
      setting is dependent on a functioning immune system. By understanding the
      mechanisms contributing to surgery-induced immunosuppression, surgeons may
      undertake strategies to minimise its effect and reduce potential short-term and
      long-term consequences to patients.

PMID- 21195331
TI  - The uses of the iPhone for surgeons.
AB  - Mobile technology is continuously improving and it is important that all
      physicians are aware of its new advances. Smartphones have the potential to
      improve diagnostic skills and education of a surgeon. The iPhone is a popular
      type of smartphone in the market. This article intends to educate surgeons about
      its uses, functions and medical applications. The phone is an invaluable tool for
      the modern day surgeon.

PMID- 21195332
TI  - Nonparasitic splenic cysts in children: Current status.
AB  - BACKGROUND: at present, the management of nonparasitic splenic (NPS) cysts in
      children is not well described in literature. The aim of this study was to
      evaluate the current status of NPS cysts in the world literature and develop some
      higher level of evidence in the management of this disease entity. In this study,
      we have also included our experience with NPS cysts. METHODS: a systematic study
      of NPS cysts published in the English literature, between the periods of 1989
      2008, was performed. The data were analyzed with respect to the type of cysts,
      mode of presentation, patient's demography, management modalities and
      complications. Data were quoted as median and range. Categorical data were
      analyzed using Chi(2) tests. P value <= 0.05 was considered as significant. All
      children, who presented to us with NPS cysts during the last 20 years, were
      reviewed and followed up till December 2009. RESULTS: after critical review of
      249 abstracts, 25 studies (retrospective 13, cases reports 11 and prospective
      study 1) were finally included in this project. This included a total of 166
      patients. The types of cysts were congenital (82%), traumatic (15%) and
      hamartomatous (3%). Male to female ratio was one to one. Median age of
      presentation was 11 years. Abdominal pain was the main complaint in 46% cases.
      Forty seven percent of the cysts were diagnosed incidentally. History of trauma
      was present in 11% cases. 1% cases were operated on due to the rupture of the
      cysts. Open procedures were performed in 60% cases [11% (total splenectomy), 29%
      (partial splenectomy) and 20% (cystectomy)]. Laparoscopic procedures were
      performed in the rest 40% cases [2% (total splenectomy), 4% (partial splenectomy)
      and 34% (cystectomy/partial decapsulation/unroofing)]. Median follow up period
      was 24 months (range 3-96 months). Recurrences were seen in only 2% of open
      procedures as Opposed to 41% in laparoscopic procedures (P<0.0001). Looking at
      the laparoscopic procedures individually, all the recurrences were seen in
      patients who had had cystectomy/partial decapsulation/unroofing. We treated 7
      children (4 males and 3 females), who had a median age of 11 years (range 1-14
      years); two of whom presented with large cysts having a diameter of 25 cm and 15
      cm, respectively. They underwent open partial splenectomy without recurrence. The
      other five children had small cysts having a diameter of <5cm and they were
      asymptomatic. Presently, the children with small cysts are being followed up
      conservatively, with no concerns so far. CONCLUSIONS: congenital cysts are the
      most common NPS cysts in children. About half of the cysts are diagnosed
      incidentally. For bigger cysts, either open or laparoscopic partial splenectomy
      is the procedure of choice. Laparoscopic-cystectomy/partial
      decapsulation/unroofing procedures have unacceptably higher recurrence rates and
      hence should not be recommended. Smaller cysts (< 5 cm diameter) can be treated
      conservatively with regular ultrasound follow up, but if they become symptomatic
      or progress in size, surgical intervention is indicated.

PMID- 21195333
TI  - Use of a simple foot support and flexing the ipsilateral hip and knee assists
      access to the lateral malleolus.

PMID- 21195335
TI  - 'Variation of laparoscopic hernia repair in Scotland: a postcode lottery?' - but
      who won the lottery?

PMID- 21195334
TI  - The European working time directive has a negative impact on surgical training in
      the UK.

PMID- 21195337
TI  - The diagnosis and management of common childhood orthopaedic disorders; medical
      imaging of common orthopedic conditions in childhood. Foreword.

PMID- 21195338
TI  - The diagnosis and management of common childhood orthopedic disorders.
AB  - Musculoskeletal illness represents a significant portion of office visits to
      primary care physicians. Despite this, little emphasis is placed on learning
      pediatric orthopedics during medical school or residency. Many articles have been
      written on selected disorders, or approaches to common conditions, such as the
      limping child. Sometimes determining where to start and how to move toward a
      diagnosis prevents prompt evaluation, referral, and treatment. Based on the
      author's experience as a general pediatrician trained in, and exclusively
      practicing, nonoperative pediatric orthopedics, approaches to selected complaints
      related to the musculoskeletal system are presented. Emphasis is placed on
      conditions resulting in frequent consultation with pediatric orthopedists from
      pediatricians and other primary care practitioners, either in the office or over
      the phone. Important features that may not be familiar to the primary care
      physician are highlighted, including the identification of aspects that require
      further evaluation and indications for consultation. Guidance regarding in-office
      management is also provided.

PMID- 21195339
TI  - Medical imaging of common orthopedic conditions in childhood.

PMID- 21195340
TI  - A new role for a metabolic star: AMP-activated protein kinase stimulates fat
      absorption.
AB  - AMPK is a kinase involved in cell energy homeostasis. In this issue of Cell
      Metabolism, Chopra and colleagues (2011) reveal a new function of AMPK in
      stimulating fat absorption. AMPK enhances the expression of the bile acid
      transporter, BSEP, by activating the coactivator SRC-2, thus promoting bile acid
      secretion.

PMID- 21195341
TI  - Heart-healthy hypertrophy.
AB  - Exercise induces growth of heart muscle cells and heart size. A new report in
      Cell (Bostrom et al., 2010) suggests that mice also respond to exercise with
      increased cardiac myocyte proliferation, and the molecular regulators of this
      pathway are linked to maladaptive and pathologic responses to cardiac stresses
      such as pressure overload.

PMID- 21195342
TI  - The etiology of Paget's disease of bone: viral and genetic interactions.
AB  - Studies of the etiology of Paget's disease have focused separately on the viral
      and genetic components of the disease. In this issue of Cell Metabolism, Kurihara
      et al. (2011) join these components, reporting that sequestosome 1 mutation in
      patients and mice activates osteoclasts, while measles virus induces the
      phenotype of Paget's disease.

PMID- 21195343
TI  - FTO and obesity: the missing link.
AB  - Genome-wide association studies revealed that variants within FTO (fat-mass- and
      obesity-associated) are strongly associated with obesity susceptibility. A recent
      study in Nature Genetics (Church et al., 2010) demonstrates that mice
      overexpressing fto exhibit a dose-dependent increase in body weight, confirming a
      role for FTO in the development of obesity.

PMID- 21195344
TI  - The tumor suppressor LKB1 emerges as a critical factor in hematopoietic stem cell
      biology.
AB  - How cellular metabolism regulates stem cell function is poorly understood but is
      an emerging field of study. In a recent issue of Nature, three independent groups
      demonstrate that LKB1 promotes hematopoietic stem cell (HSC) quiescence and
      metabolic homeostasis. Surprisingly, these effects on HSCs occur independently of
      AMPK/mTOR and FoxO signaling.

PMID- 21195345
TI  - NF-kappaB, inflammation, and metabolic disease.
AB  - Metabolic disorders including obesity, type 2 diabetes, and atherosclerosis have
      been viewed historically as lipid storage disorders brought about by
      overnutrition. It is now widely appreciated that chronic low-grade inflammation
      plays a key role in the initiation, propagation, and development of metabolic
      diseases. Consistent with its central role in coordinating inflammatory
      responses, numerous recent studies have implicated the transcription factor NF
      kappaB in the development of such diseases, thereby further establishing
      inflammation as a critical factor in their etiology and offering hope for the
      development of new therapeutic approaches for their treatment.

PMID- 21195346
TI  - Contributions of the measles virus nucleocapsid gene and the SQSTM1/p62(P392L)
      mutation to Paget's disease.
AB  - Paget's disease (PD) is characterized by abnormal osteoclasts (OCL) that secrete
      high IL-6 levels and induce exuberant bone formation. Because measles virus
      nucleocapsid gene (MVNP) and the p62(P392L) mutation are implicated in PD,
      marrows from 12 PD patients harboring p62(P392L) and eight normals were tested
      for MVNP expression and pagetic OCL formation. Eight out of twelve patients
      expressed MVNP and formed pagetic OCL in vitro, which were inhibited by antisense
      MVNP. Four out of twelve patients lacked MVNP and formed normal OCL that were
      hyperresponsive to RANKL but unaffected by antisense-MVNP. Similarly, mice
      expressing only p62(P394L) formed normal OCL, while mice expressing MVNP in OCL,
      with or without p62(P394L), developed pagetic OCL and expressed high IL-6 levels
      dependent on p38MAPK activation. IL-6 deficiency in MVNP mice abrogated pagetic
      OCL development in vitro. Mice coexpressing MVNP and p62(P394L) developed
      dramatic Paget's-like bone lesions. These results suggest that p62(P394L) and IL
      6 induction by MVNP play key roles in PD.

PMID- 21195348
TI  - Inhibition of SREBP by a small molecule, betulin, improves hyperlipidemia and
      insulin resistance and reduces atherosclerotic plaques.
AB  - Sterol regulatory element-binding proteins (SREBPs) are major transcription
      factors activating the expression of genes involved in biosynthesis of
      cholesterol, fatty acid and triglyceride. In this study, we identified a small
      molecule, betulin, that specifically inhibited the maturation of SREBP by
      inducing interaction of SREBP cleavage activating protein (SCAP) and Insig.
      Inhibition of SREBP by betulin decreased the biosynthesis of cholesterol and
      fatty acid. In vivo, betulin ameliorated diet-induced obesity, decreased the
      lipid contents in serum and tissues, and increased insulin sensitivity.
      Furthermore, betulin reduced the size and improved the stability of
      atherosclerotic plaques. Our study demonstrates that inhibition SREBP pathway can
      be employed as a therapeutic strategy to treat metabolic diseases including type
      II diabetes and atherosclerosis. Betulin, which is abundant in birch bark, could
      be a leading compound for development of drugs for hyperlipidemia.

PMID- 21195347
TI  - Cellular energy depletion resets whole-body energy by promoting coactivator
      mediated dietary fuel absorption.
AB  - All organisms have devised strategies to counteract energy depletion and promote
      fitness for survival. We show here that cellular energy depletion puts into play
      a surprising strategy that leads to absorption of exogenous fuel for energy
      repletion. The energy-depletion-sensing kinase AMPK binds, phosphorylates, and
      activates the transcriptional coactivator SRC-2, which in a liver-specific manner
      promotes absorption of dietary fat from the gut. Hepatocyte-specific deletion of
      SRC-2 results in intestinal fat malabsorption and attenuated entry of fat into
      the blood stream. This defect can be attributed to AMPK- and SRC-2-mediated
      transcriptional regulation of hepatic bile acid (BA) secretion into the gut, as
      it can be completely rescued by replenishing intestinal BA or by genetically
      restoring the levels of hepatic bile salt export pump (BSEP). Our results
      position the hepatic AMPK-SRC-2 axis as an energy rheostat, which upon cellular
      energy depletion resets whole-body energy by promoting absorption of dietary
      fuel.

PMID- 21195349
TI  - Decoupling ferritin synthesis from free cytosolic iron results in ferritin
      secretion.
AB  - Ferritin is a multisubunit protein that is responsible for storing and
      detoxifying cytosolic iron. Ferritin can be found in serum but is relatively iron
      poor. Serum ferritin occurs in iron overload disorders, in inflammation, and in
      the genetic disorder hyperferritinemia with cataracts. We show that ferritin
      secretion results when cellular ferritin synthesis occurs in the relative absence
      of free cytosolic iron. In yeast and mammalian cells, newly synthesized ferritin
      monomers can be translocated into the endoplasmic reticulum and transits through
      the secretory apparatus. Ferritin chains can be translocated into the endoplasmic
      reticulum in an in vitro translation and membrane insertion system. The insertion
      of ferritin monomers into the ER occurs under low-free-iron conditions, as iron
      will induce the assembly of ferritin. Secretion of ferritin chains provides a
      mechanism that limits ferritin nanocage assembly and ferritin-mediated iron
      sequestration in the absence of the translational inhibition of ferritin
      synthesis.

PMID- 21195350
TI  - Mice with AS160/TBC1D4-Thr649Ala knockin mutation are glucose intolerant with
      reduced insulin sensitivity and altered GLUT4 trafficking.
AB  - AS160 has emerged as a key player in insulin-mediated glucose transport through
      controlling GLUT4 trafficking, which is thought to be regulated by insulin
      stimulated phosphorylation of sites including the 14-3-3 binding phospho-Thr649
      (equivalent to Thr642 in human AS160). To define physiological roles of AS160
      Thr649 phosphorylation and 14-3-3 binding in glucose homeostasis, we substituted
      this residue by a nonphosphorylatable alanine by knockin mutation in mice. The
      mutant protein was expressed at normal levels, while insulin-stimulated AS160
      binding to 14-3-3s was abolished in homozygous knockin mice. These animals
      displayed impaired glucose disposal and insulin sensitivity, which were
      associated with decreased glucose uptake in vivo. Insulin-stimulated glucose
      transport and cell surface GLUT4 content were reduced in isolated muscles, but
      not in adipocytes. These results provide genetic evidence that insulin-induced
      AS160-Thr649 phosphorylation and/or its binding to 14-3-3 play an important role
      in regulating whole-body glucose homeostasis, at least in part through regulating
      GLUT4 trafficking in muscle.

PMID- 21195351
TI  - A common variant in TFB1M is associated with reduced insulin secretion and
      increased future risk of type 2 diabetes.
AB  - Type 2 diabetes (T2D) evolves when insulin secretion fails. Insulin release from
      the pancreatic beta cell is controlled by mitochondrial metabolism, which
      translates fluctuations in blood glucose into metabolic coupling signals. We
      identified a common variant (rs950994) in the human transcription factor B1
      mitochondrial (TFB1M) gene associated with reduced insulin secretion, elevated
      postprandial glucose levels, and future risk of T2D. Because islet TFB1M mRNA
      levels were lower in carriers of the risk allele and correlated with insulin
      secretion, we examined mice heterozygous for Tfb1m deficiency. These mice
      displayed lower expression of TFB1M in islets and impaired mitochondrial function
      and released less insulin in response to glucose in vivo and in vitro. Reducing
      TFB1M mRNA and protein in clonal beta cells by RNA interference impaired
      complexes of the mitochondrial oxidative phosphorylation system. Consequently,
      nutrient-stimulated ATP generation was reduced, leading to perturbed insulin
      secretion. We conclude that a deficiency in TFB1M and impaired mitochondrial
      function contribute to the pathogenesis of T2D.

PMID- 21195352
TI  - Enteric neurons and systemic signals couple nutritional and reproductive status
      with intestinal homeostasis.
AB  - The gastrointestinal tract is emerging as a key regulator of appetite and
      metabolism, but daunting neuroanatomical complexity has hampered identification
      of the relevant signals. Invertebrate models could provide a simple and
      genetically amenable alternative, but their autonomic nervous system and its
      visceral functions remain largely unexplored. Here we develop a quantitative
      method based on defecation behavior to uncover a central role for the Drosophila
      intestine in the regulation of nutrient intake, fluid, and ion balance. We then
      identify a key homeostatic role for autonomic neurons and hormones, including a
      brain-gut circuit of insulin-producing neurons modulating appetite, a vasopressin
      like system essential for fluid homeostasis, and enteric neurons mediating sex
      peptide-induced changes in intestinal physiology. These conserved mechanisms of
      visceral control, analogous to those found in the enteric nervous system and
      hypothalamic/pituitary axis, enable the study of autonomic control in a model
      organism that has proved instrumental in understanding sensory and motor systems.

PMID- 21195354
TI  - Gender medicine and mental health-A challenge for psychiatry.

PMID- 21195353
TI  - Deficiency of lipoprotein lipase in neurons modifies the regulation of energy
      balance and leads to obesity.
AB  - Free fatty acids (FFAs) suppress appetite when injected into the hypothalamus. To
      examine whether lipoprotein lipase (LPL), a serine hydrolase that releases FFAs
      from circulating triglyceride (TG)-rich lipoproteins, might contribute to FFA
      mediated signaling in the brain, we created neuron-specific LPL-deficient mice.
      Homozygous mutant (NEXLPL-/-) mice were hyperphagic and became obese by 16 weeks
      of age. These traits were accompanied by elevations in the hypothalamic
      orexigenic neuropeptides, AgRP and NPY, and were followed by reductions in
      metabolic rate. The uptake of TG-rich lipoprotein fatty acids was reduced in the
      hypothalamus of 3-month-old NEXLPL-/- mice. Moreover, deficiencies in essential
      fatty acids in the hypothalamus were evident by 3 months, with major deficiencies
      of long-chain n-3 fatty acids by 12 months. These results indicate that TG-rich
      lipoproteins are sensed in the brain by an LPL-dependent mechanism and provide
      lipid signals for the central regulation of body weight and energy balance.

PMID- 21195356
TI  - Effects of gender in amyotrophic lateral sclerosis.
AB  - BACKGROUND: There is evidence that amyotrophic lateral sclerosis (ALS), also
      known as motor neuron disease (MND), is more common in men than in women and that
      gender influences the clinical features of the disease. The causes of this are
      unknown. OBJECTIVE: This review examines the gender differences that are found in
      ALS and postulates reasons for these differences. METHODS: A literature review of
      PubMed (with no date limits) was performed to find information about gender
      differences in the incidence, prevalence, and clinical features of ALS, using the
      search terms ALS or MND and gender or sex, ALS prevalence, and SOD1 mice and
      gender. Articles were reviewed for information about gender differences, together
      with other articles that were already known to the authors. RESULTS: The
      incidence and prevalence of ALS are greater in men than in women. This gender
      difference is seen in large studies that included all ALS patients (sporadic and
      familial), but is not seen when familial ALS is studied independently. Men
      predominate in the younger age groups of patients with ALS. Sporadic ALS has
      different clinical features in men and women, with men having a greater
      likelihood of onset in the spinal regions, and women tending to have onset in the
      bulbar region. Gender appears to have no clear effect on survival. In animals
      with superoxide dismutase 1 (sod1) mutations, sex does affect the clinical course
      of disease, with earlier onset in males. Possible reasons for the differences in
      ALS between men and women include different exposures to environmental toxins,
      different biological responses to exogenous toxins, and possibly underlying
      differences between the male and female nervous systems and different abilities
      to repair damage. CONCLUSIONS: There is a complex interaction between gender and
      clinical phenotypes in ALS. Understanding the causes of the gender differences
      could give clues to processes that modify the disease.

PMID- 21195355
TI  - Risk factors for cardiovascular disease in women with diabetes.

PMID- 21195357
TI  - Sex-specific differences in metabolic control, cardiovascular risk, and
      interventions in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Sex-specific differences appear particularly relevant in the
      management of type 2 diabetes mellitus (T2DM), with women experiencing greater
      increases in cardiovascular morbidity and mortality than do men. OBJECTIVE: The
      aim of this article was to investigate the influence of biological sex on
      clinical care and microvascular and macrovascular complications in patients with
      T2DM in a Central European university diabetes clinic. METHODS: In a cross
      sectional study, sex-specific disparities in metabolic control, cardiovascular
      risk factors, and diabetic complications, as well as concomitant medication use
      and adherence to treatment recommendations, were evaluated in 350 consecutive
      patients who were comparable for age, diabetes duration, and body mass index.
      Study inclusion criteria included age <=75 years, T2DM, a documented history of
      presence or absence of coronary heart disease (CHD), and informed consent.
      Patients were followed in the diabetes outpatient clinic between November 2007
      and March 2008. RESULTS: Two hundred and one patients with T2DM met inclusion
      criteria (93 [46.3%] women, 108 [53.7%] men). Women with T2DM had higher mean
      (SE) systolic blood pressure (155.4 [22.5] vs 141.0 [19.8] mm Hg for men; P <
      0.001) and total cholesterol (TC) (5.28 [1.34] vs 4.86 [1.29] mmol/L for men; P <
      0.05), but a lower TC:HDL-C ratio (4.1 [1.19] vs 4.5 [1.2] for men; P < 0.05).
      Slightly more men (32.4%) than women (26.9%) reached the therapeutic goal of
      <7.0% for glycosylated hemoglobin. Women with shorter diabetes duration (<10
      years) received oral antihyperglycemic therapy less frequently (P < 0.05). Women
      with longer disease duration had hypertension more frequently than did their male
      counterparts (100% vs 86.0%, respectively; P < 0.01). Despite a similar rate of
      CHD, men were twice as likely as women to have had coronary interventions
      (percutaneous transluminal coronary angioplasty/coronary artery bypass graft,
      25.0% vs 12.9%, respectively; P < 0.05). Women with CHD also had a higher rate of
      cerebral ischemia than did men (27.6% vs 5.4%, respectively; P < 0.05) and
      received aspirin less frequently for secondary prevention (P < 0.001). Men had
      greater overall adherence to diabetes and cardiovascular risk guidelines than did
      women (66.4% vs 58.9%, respectively; P < 0.01). CONCLUSIONS: In this study of
      diabetes clinic outpatients, women with T2DM had a worse cardiovascular risk
      profile and achieved therapeutic goals less frequently than did men. Treatment
      strategies should be improved in both sexes, but women with diabetes may be in
      need of more aggressive treatment, especially when cardiovascular disease is
      present.

PMID- 21195358
TI  - Preoperative stress testing in high-risk vascular surgery and its association
      with gender.
AB  - BACKGROUND: Despite significant improvement in anesthetic and surgical
      techniques, the incidence of perioperative myocardial infarction (PMI) and all
      cause mortality from any cardiac event during high-risk vascular surgery
      (abdominal aortic or infrainguinal revascularization procedures) remains high. In
      addition, there are significant health care costs associated with the management
      of PMI. OBJECTIVES: The aim of this analysis was to investigate the utility of
      routine preoperative myocardial stress testing prior to high-risk vascular
      surgery and the interventions performed based on the results of the testing. The
      outcome after surgery, based on sex of the patients, was also examined. METHODS:
      A retrospective analysis was performed on consecutive adult patients who had a
      positive dipyridamole-thallium stress test prior to high-risk vascular surgery in
      a university hospital (tertiary care center) between July 2001 and August 2004.
      The patients' preoperative demographic characteristics, perioperative record, and
      postoperative course in the hospital were analyzed. Combined major adverse
      outcome was defined as any incidence of MI, congestive heart failure,
      arrhythmias, renal failure, or death. RESULTS: Of a total of 503 patients, 160
      had a positive stress test prior to high-risk vascular surgery (111 men, 49
      women; mean [SD] age, 68 [11] and 70 [12] years, respectively). Men with a
      positive stress test who had either coronary intervention or perioperative beta
      blockade prior to surgery had a significant decrease in the incidence of combined
      major adverse outcomes (P = 0.02). Conversely, women did not have a significant
      improvement in outcome with either of the preoperative strategies. Using logistic
      regression, only age and conservative management in men were found to be
      predictors of adverse outcomes. CONCLUSIONS: In this small retrospective study,
      men with positive stress tests had fewer adverse events with either preoperative
      coronary revascularization or perioperative administration of beta-adrenergic
      blocking drugs, compared with men who received no intervention. There were no
      significant differences in adverse outcomes between women with positive stress
      tests who received either treatment compared with those who did not receive any
      treatment.

PMID- 21195359
TI  - Sex-specific differences in glycemic control and cardiovascular risk factors in
      older patients with insulin-treated type 2 diabetes mellitus.
AB  - BACKGROUND: Because women have been excluded from many study populations in
      investigations of diabetes care, there is insufficient information on sex
      specific differences in glycemic control. OBJECTIVE: The aim of the present study
      was to assess whether treatment goals for glycemic and cardiovascular risk factor
      control are achieved equally in older, Central European, female and male patients
      with type 2 diabetes mellitus (T2DM). METHODS: In a retrospective cross-sectional
      study, data were analyzed from consecutive older (aged >=60 years) female and
      male patients with insulin-treated T2DM who attended a diabetes outpatient clinic
      between January 2007 and April 2008 at the Medical University of Vienna, Austria.
      Sex-specific differences in glycosylated hemoglobin (HbA1(c)) levels were
      assessed as the primary outcome. LDL-C and HDL-C, as well as systolic and
      diastolic blood pressure (SBP and DBP, respectively), were assessed as secondary
      outcomes and were adjusted for age, duration of diabetes, duration of insulin
      treatment, body mass index, insulin units per kilogram per day, and secondary
      causes of diabetes. P values were adjusted using the Bonferroni correction.
      RESULTS: Data were analyzed from 183 female and 209 male patients with insulin
      treated T2DM. In multivariate linear regression models, women had significantly
      higher levels of LDL-C (P = 0.008), HDL-C (P < 0.001), SBP (P < 0.001), and DBP
      (P = 0.034), but not HbA1(c) (P = NS). Multivariate logistic regression models
      revealed that women were significantly less likely to meet treatment goals for
      blood pressure (SBP, P = 0.044; DBP, P = 0.024), but not for cholesterol or
      HbA1(c) levels (P = NS for LDL-C, HDL-C, and HbA1(c)). CONCLUSION: In this study
      of older patients with insulin-treated T2DM, whereas glycemic control was
      comparable between women and men, a more adverse cardiovascular risk factor
      profile was observed in female patients.

PMID- 21195360
TI  - Earlier development of diabetic neuropathy in men than in women with type 2
      diabetes mellitus.
AB  - BACKGROUND: Data about the prevalence of diabetic neuropathy (DN) differ
      substantially, depending on the population and diagnostic methods. Sex-specific
      differences in DN are rarely discussed. OBJECTIVES: The aims of the present study
      were to assess the prevalence of, and analyze sex differences in, DN in a
      hospital population with type 2 diabetes mellitus (T2DM) over a period of 18
      years. METHODS: In this retrospective study performed at a university hospital
      endocrinology clinic in Sofia, patient clinical records from 1990-2007 were
      examined. Patients were included in the database only at their first admission.
      RESULTS: Data from 1705 patients with T2DM were analyzed (961 women, 744 men;
      mean [SD] age, 60.0 [11.9] years; diabetes duration, 9.9 [8.4] years;
      glycosylated hemoglobin, 9.0% [2.2%]; and body mass index, 29.4 [6.0] kg/m2).
      Obesity (46.3% vs 32.0%; P < 0.001), hypertension (86.7% vs 77.8%; P < 0.001),
      and dyslipidemia (61.2% vs 55.0%; P < 0.05) were significantly more common in
      women than in men, respectively. The prevalence of DN was 78.8%, with no
      significant sex differences. However, prevalence differed with time,
      corresponding to the frequency of application of electrophysiologic
      (electromyograms) or semiquantitative instrumental diagnostic methods. In men,
      the median (25th-75th percentiles) interval between diagnosis of T2DM and
      diagnosis of DN was 6 (1-12) years; in women, the interval was 8 (4-13) years (P
      < 0.01). CONCLUSIONS: In this study of Bulgarian patients with T2DM, women were
      at higher macrovascular risk than were men. A high prevalence of DN was observed
      among these patients. The period from the diagnosis of T2DM to DN was shorter in
      men than in women-this necessitates earlier screening and therapeutic
      intervention for DN in men. Reasons for this sex difference may include
      differences in lifestyle and the testosterone deficiency that is common in men
      with diabetes, leading to a more pronounced deficit of neurosteroids.

PMID- 21195361
TI  - Gender differences in the accuracy of time-dependent blood pressure indices for
      predicting coronary heart disease: A random-effects modeling approach.
AB  - BACKGROUND: Previous studies on blood pressure (BP) indices as a predictor of
      coronary heart disease (CHD) have provided equivocal results and generally relied
      on Cox proportional hazards regression methodology, with age and sex accounting
      for most of the predictive capability of the model. OBJECTIVE: The aim of the
      present study was to use serially collected BP measurements to examine age-and
      gender-related differences in BP indices for predicting CHD. METHODS: The
      predictive accuracy of time-dependent BP indices for CHD was investigated using a
      method of risk prediction based on posterior probabilities calculated from mixed
      effects regression to utilize intraindividual differences in serial BP
      measurements according to age changes within gender groups. Data were collected
      prospectively from 2 community-dwelling cohort studies in the United States
      (Baltimore Longitudinal Study of Aging [BLSA]) and Europe (Vorarlberg Health
      Monitoring and Promotion Program [VHM&PP]). RESULTS: The study comprised 152,633
      participants (aged 30-74 years) and 610,061 BP measurements. During mean follow
      up of 7.5 years, 2457 nonfatal and fatal CHD events were observed. In both study
      populations, pulse pressure (PP) and systolic blood pressure (SBP) performed best
      as individual predictors of CHD in women (area under the receiver operating
      characteristic curve [AUC(ROC)] was between 0.83 and 0.85 for PP, and between
      0.77 and 0.81 for SBP). Mean arterial pressure (MAP) and diastolic blood pressure
      (DBP) performed better for men (AUC(ROC) = 0.67 and 0.65 for MAP and DBP,
      respectively, in the BLSA; AUC(ROC) = 0.77 and 0.75 in the VHM&PP) than for women
      (AUC(ROC) = 0.60 for both MAP and DBP in the BLSA; AUC(ROC) = 0.75 and 0.52,
      respectively, in the VHM&PP). The degree of discrimination in both populations
      was overall greater but more varied for all BP indices for women (AUC(ROC)
      estimates between 0.85 [PP in the VHM&PP] and 0.52 [DBP in the VHM&PP]) than for
      men (AUC(ROC) estimates between 0.78 [MAP + PP in the VHM&PP] and 0.63 [PP in the
      BLSA]). CONCLUSION: Our findings indicate differences in discrimination between
      women and men in the accuracy of longitudinally collected BP measurements for
      predicting CHD, implicating the usefulness of gender-specific BP indices to
      assess individual CHD risk.

PMID- 21195362
TI  - Digit ratios and relation to myocardial infarction in Greek men and women.
AB  - BACKGROUND: Digit ratios, such as the second to fourth digit ratio (2D:4D), are
      biometric markers that are influenced by estrogen and testosterone concentrations
      in utero and are determined genetically by HOX genes (homeodomain-containing
      homeotic genes). Sex steroids also play a crucial role in the occurrence of
      myocardial infarction (MI), which is considered to be gender dependent and
      related to testosterone. Additionally, first-trimester exposure to excess levels
      of estrogens and progesterone has been linked to cardiovascular anomalies.
      OBJECTIVE: The aim of this work was to study digit ratios in a Greek population
      and assess their clinical importance as markers of predisposition to MI. METHODS:
      Two samples were used: a group of Greek men and women hospitalized with MI, and a
      control group of healthy Greek men and women of the same age. Finger lengths were
      measured twice for both hands using electronic calipers. In the results, digits
      were designated as 2D (second digit), 3D (third digit), 4D (fourth digit), and 5D
      (fifth digit). RESULTS: A total of 50 Greek men and 50 Greek women with MI were
      recruited (mean [SD] age, 69.3 [11.2] years for men; 69.7 [11.0] years for
      women). The control group consisted of 40 healthy Greek men and 40 healthy Greek
      women (mean age, 68.0 [11.8] years for men; 66.8 [10.7] years for women). In the
      control group, 2D:4D, 2D:3D, and 2D:5D ratios were significantly higher in women
      than in men (2D:4D: right hand, P < 0.001; left hand, P = 0.002; 2D:3D: right
      hand, P < 0.001; left hand, P = 0.003; 2D:5D: right hand, P < 0.001; left hand, P
      < 0.05). The mean values of 2D:4D ratios appeared to increase in the following
      order: healthy men < men with MI < healthy women < women with MI, although this
      difference was not statistically significant. In men with MI, 2D:4D and 3D:4D
      ratios were significantly higher than the respective ratios in healthy men
      (2D:4D: right hand, P = 0.001; left hand, P < 0.05; 3D:4D: right hand, P < 0.05;
      left hand, P = 0.001), but no significant differences were observed in the ratios
      between women with MI and healthy women. CONCLUSIONS: Digit ratios that include
      ring-finger length (ie, 4D) may be useful biomarkers for predisposition to MI in
      Greek men, but not in Greek women. Sexual dimorphism of digit ratios was present
      in both groups and was independent of the individuals' health status.

PMID- 21195363
TI  - Burden among male caregivers assisting people with multiple sclerosis.
AB  - BACKGROUND: Caregiver burden is a multidimensional response to many factors
      associated with providing assistance to people with multiple sclerosis (MS),
      including physical, psychological, emotional, and social stressors. OBJECTIVE:
      The aim of this analysis was to identify the characteristics of male informal
      caregivers, the assistance provided, and the people receiving assistance who were
      associated with the burden of care. METHODS: Data were collected from a national
      survey (which included the Mental Component Summary of the SF-8 Health Survey) of
      informal caregivers and analyzed using an ordered logistic regression model to
      identify characteristics associated with burden among male informal caregivers.
      RESULTS: Greater burden among male caregivers was associated with significantly
      greater hours per week providing assistance (P = 0.009) and significantly greater
      restriction on the caregiver's ability to perform daily activities (P < 0.001)
      due to assisting the person with MS. We found a strong association between the
      perception of burden and the mental health status of the male caregiver (P <
      0.001). CONCLUSIONS: Our findings highlight the strong association of caregiver
      burden and the Mental Component Summary of the SF-8. Reducing burden may improve
      the mental health of informal caregivers. Health professionals treating either
      male caregivers or people with MS should be sensitive to the impact that
      providing assistance has on the mental health of informal caregivers.

PMID- 21195365
TI  - Hepatitis B virus. Introduction.

PMID- 21195366
TI  - HDV: thirty years later.
AB  - The hepatitis D virus (HDV) was discovered in Italy in the mid-1970s during a
      major outbreak of hepatitis D in the Mediterranean basin. The outbreak has been
      brought under control in Europe and throughout the industrialized world in the
      last twenty years; in parallel, the clinical pattern of HDV disease has
      consistently changed. Though the decline of hepatitis D has diminished attention
      to this problem and at present testing for HDV is not seldom neglected, hepatitis
      D is not eradicated in Europe and its circulation did not decline further in the
      last decade. Fresh new cases are cumulating in migrants from HDV endemic areas of
      the developing world. Hepatitis D remains a major health problem in many
      developing areas with outbreaks of the disease continuing to be reported from
      Asia, Africa and South Africa.

PMID- 21195367
TI  - Hepatitis delta virus infection: open issues.
AB  - Hepatitis delta virus (HDV) consists of a circular single-stranded RNA genome
      which assembles two viral proteins and acquires a lipid envelope in which the
      hepatitis B surface antigens (HBsAg) are embedded. HDV does not encode its own
      polymerase, but exploits a cellular enzyme for its replication. A better
      understanding of the mechanisms of HDV replication mechanism would provide new
      insights for antiviral strategies. Based on genomic variability, eight major
      genotypes of HDV have been identified, which differ as much as 40% in the
      nucleotide sequence. The cloning of HDV-RNA has provided genetic probes for the
      measurement of HDV-RNA in serum and liver; the sensitivity of HDV-RNA detection
      improved significantly when the reverse transcriptase-polymerase chain reaction
      (PCR) technique was introduced. As no commercial test is standardized for viral
      load detection, home-made assays have been developed in the different referral
      centers, which may not be comparable. Quantification of HDV in serum by real-time
      PCR has been recently proposed in the management of chronically infected
      patients. No specific inhibitors of HDV are available at present and, in spite of
      the crucial relationship between HDV and HBV, drugs that block HBV have only a
      theoretical but no sound effect on HDV replication.

PMID- 21195368
TI  - The worldwide impact of vaccination on the control and protection of viral
      hepatitis B.
AB  - Viral hepatitis B is a leading cause of acute and chronic liver disease
      worldwide, including cirrhosis and hepatocellular carcinoma. Vaccination is the
      most effective measure for controlling and preventing hepatitis B and its severe
      long-term sequelae. According to the World Health Organization (WHO), by the end
      of 2008 177 countries had introduced hepatitis B vaccination into their national
      routine neonatal, infant and/or adolescent immunisation programmes, and Italy was
      one of the first countries to implement a universal strategy of hepatitis B
      vaccination. The implementation of such vaccination programmes has globally
      resulted in a marked decrease in disease burden, in the carrier rate and in
      hepatitis B-related morbidity and mortality. Despite this success, work remains
      to be done to fully achieve the WHO goal of control of hepatitis B and HBV
      related diseases on a global scale.

PMID- 21195369
TI  - The role of transient elastography in patients with hepatitis B viral disease.
AB  - This review focuses on the role of ultrasound and transient elastography (TE) in
      patients with hepatitis B virus (HBV) infection. Among the ultrasonographic signs
      analyzed, liver surface nodularity has the highest diagnostic accuracy and is
      particularly useful in confirming the presence of severe fibrosis or cirrhosis,
      due to its high specificity. The role of TE in patients with hepatitis B virus
      disease was assessed in inactive carriers and patients with chronic liver disease
      (CHB). In inactive HBV carriers, mean TE values are similar to normal controls
      and significantly lower than in patients with CHB. In this latter group, the
      available studies showed a significant positive correlation between TE values and
      fibrosis stages at liver histology. However, as for HCV patients, there is a
      certain degree of overlap among the lower stages of hepatic fibrosis and the
      accuracy of this technique is not optimal for the diagnosis of significant
      fibrosis, whereas its diagnostic performances are higher for the diagnosis of
      liver cirrhosis. The development of diagnostic algorithms, with a confirmatory
      and an exclusion liver stiffness threshold, seems to be a promising tool for a
      correct classification of patients.

PMID- 21195370
TI  - HBV-related HCC, clinical issues and therapy.
AB  - Every year, more than 600 thousand persons will develop hepatocellular carcinoma
      (HCC) worldwide. Sixty percent of all HCCs in Asia and Africa are related to
      chronic infection with the hepatitis B virus (HBV) compared to only 20% of HCC
      cases in Europe, Japan and USA. Surveillance of chronically infected patients
      improves treatment of HCC, since it helps detecting tumors amenable to radical
      therapies. In cirrhotic patients, HCC can be confidently diagnosed by contrast
      imaging techniques, albeit the accuracy of radiological diagnosis is largely
      influenced by tumor size. Hepatic resection and liver transplantation are the
      first therapeutic options for patients within Milan criteria. The long-term
      outcome of resection, however, is affected by high risk of tumor recurrence,
      whereas liver transplantation has a negligible risk of both HBV and HCC
      recurrence-related anticipated mortality. The clinical benefits of loco-regional
      ablative techniques are evidence based for patients with less than 3 cm tumors
      only, whereas the standard of care for intermediate tumors, chemoembolization,
      needs to be validated in view of new technical improvements. Tertiary prevention
      of HCC in patients with established HBV infection is doubtful, mainly due to
      methodological weaknesses of studies based on interferon and nucleos(t)ide
      analogues therapy.

PMID- 21195371
TI  - Hepatitis B virus infection and immunosuppressive therapy in patients with
      inflammatory bowel disease.
AB  - Hepatitis B reactivation has been widely reported in patients undergoing
      immunosuppressive therapy in oncohaematological and transplant settings, with a
      high frequency of hepatic failure. This topic has received growing scientific
      interest and several studies reported the preventive effect of antiviral agents
      on hepatitis B reactivation during immunosuppression therapy. Routine prophylaxis
      is therefore recommended and specific recommendations were elaborated by AASLD,
      EASL and AISF. On the contrary, few data are available on the risk of HBV
      reactivation in patients with inflammatory bowel disease (IBD) receiving
      immunosuppressive therapy, and major questions regarding the optimal management
      (screening, prophylaxis, therapy, monitoring) of IBD patients with HBV infection
      remain to be addressed. The aim of this paper is to provide a systematic review
      of the literature to underline the main aspects of HBV infection and reactivation
      in patients affected by IBD treated with conventional or biological
      immunosuppressive drugs.

PMID- 21195372
TI  - HBV disease: HBsAg carrier and occult B infection reactivation in haematological
      setting.
AB  - HBV reactivation in patients with haematological malignancies undergoing
      chemoimmunotherapy is a serious and frequent complication. This is linked to
      either the high frequency of inactive HbsAg carriers and occult B infection among
      oncohaematological patients or the profound immunosuppression caused by high dose
      chemotherapy, monoclonal antibody therapy or auto- and allo-haematopoietic stem
      cell (HSC) transplantations. Identifying the patients at risk is mandatory in
      this clinical setting and prophylaxis with antiviral drugs or close monitoring
      may reduce and/or eliminate the HBV reactivation risk and the serious
      consequences. In general, preemptive anti-HBV therapy is more effective than
      treatment at reactivation. Prompt lamivudine prophylaxis should be given to HBsAg
      positive patients (inactive carriers) undergoing chemotherapy-immunochemotherapy
      and continued after cessation of immunosuppression even though long-term
      lamivudine therapy involves a risk of developing drug resistance. Use of newer
      anti-HBV agents may be considered. HBV reactivation has also been observed in
      occult B infection (HBcAb positive) and the optimal management of this group of
      patients requires special attention.

PMID- 21195373
TI  - HBV therapy: guidelines and open issues.
AB  - Therapy of chronic hepatitis B is currently based on two different strategies:
      (a) a finite course of treatment with pegylated interferon aimed to induce a
      sustained virological response that is maintained long-term after therapy
      withdrawal and (b) an indefinite treatment with oral anti-HBV
      nucleoside/nucleotide analogues (NUCs) aimed to achieve long-term complete
      suppression of HBV replication. The first strategy is typically used in patients
      with less advanced liver disease, with high ALT and no too high HBV-DNA and is
      particularly successful in the younger patients and in those infected with HBV
      genotype A or B. The suppressive strategy is instead typically adopted for
      patients with more advanced liver disease, and for those who have failed or
      cannot tolerate interferon therapy. Recently, following the implementation of
      third generation NUCs with high antiviral potency and barrier to resistance, the
      indication of oral therapy has gained credibility and indication, although most
      guidelines still recommend to start these drugs only in the presence of
      significant and progressive liver disease. This review summarises the recent
      Recommendations produced for the treatment of chronic HBV infection, with
      particular focus on the 2010 Italian Guidelines.

PMID- 21195374
TI  - Natural history of chronic HBV infection: special emphasis on the prognostic
      implications of the inactive carrier state versus chronic hepatitis.
AB  - The evaluation of the natural history of chronic hepatitis B virus (HBV)
      infection requires the precise definition of the various clinical conditions that
      can be encountered (i.e. inactive carrier state or subject with liver disease
      activity). This can be achieved by repeat monitoring of ALT, serum HBV-DNA levels
      (over a period of at least 1 year, according to international guidelines) and/or
      evaluation of HBsAg titre. Liver biopsy may offer additional information although
      it is not mandatory. Overall, the natural history of the true inactive carrier is
      benign: reactivation of hepatitis, especially in Western countries, is rare and
      is usually due to co-factors (like alcohol or drugs); spontaneous HBsAg loss is
      frequent (around 1% per year) and HCC development rare. On the other hand, in
      patients with chronic hepatitis B or cirrhosis, the risk of reactivation, of HCC
      development and of liver-related mortality is much higher, especially in Eastern
      countries, and should therefore lead to antiviral therapy.

PMID- 21195375
TI  - Comparison of mortality rates in women versus men presenting with ST-segment
      elevation myocardial infarction.
AB  - Women who present with coronary artery disease have different characteristics,
      undergo different treatment, and have a different prognosis than men. The
      increasing use of coronary stenting has improved the outcome of percutaneous
      coronary intervention (PCI). However, little is known about the outcomes for men
      versus women after PCI, especially for those presenting with a diagnosis of acute
      coronary syndrome. Thus, we compared the baseline features, management, and long
      term outlook of men versus women undergoing PCI. All consecutive patients who had
      undergone PCI with stents at our center from July 1, 2002 to June 30, 2004 were
      identified retrospectively. The primary end point was the long-term rate of major
      adverse cardiac events (i.e., death, infarction, and repeat revascularization).
      The secondary end points were the individual components of the major adverse
      cardiac events and stent thrombosis. A total of 833 patients were included, 210
      women (25.2%) and 623 men (75.8%). The women were significantly older (70.9 vs 63
      years, p <0.001) and more often had diabetes mellitus (36.2% vs 21.0%, p <0.001)
      and hypertension (82.3% vs 73.7%, p = 0.006). The number of drug-eluting stents
      and the length were significantly lower in the female patients. The incidence of
      major adverse cardiac events after a median follow-up of 60 months was similar
      for both women and men (38.8% vs 46.4%, p = 0.075), with a trend toward greater
      mortality rate for women (21.2% vs 15.4%, p = 0.090). All other end points
      occurred with similar frequencies. Only in the subgroup of ST-segment elevation
      myocardial infarction were the rates of death significantly greater for the women
      than for the men (20.0% vs 8.1%; p = 0.029). In conclusion, very long-term follow
      up of women undergoing PCI with coronary artery stenting resulted in similar
      rates of cardiac event compared to those of men, but greater care should be given
      to women presenting with ST-segment elevation myocardial infarction. Also,
      despite their greater baseline risk profile, women were significantly less likely
      to have received effective treatment, the use of including drug-eluting stents.

PMID- 21195376
TI  - Usefulness of at rest and exercise hemodynamics to detect subclinical myocardial
      disease in type 2 diabetes mellitus.
AB  - Patients with type 2 diabetes mellitus (T2DM) might have subclinical myocardial
      dysfunction identified at rest or unmasked during exercise. We examined the
      correlates of the myocardial exercise response in patients with T2DM. Myocardial
      dysfunction was sought during at rest and exercise echocardiography in 167
      healthy patients with T2DM (97 men, 55 +/- 10 years). Myocardial ischemia was
      excluded using stress echocardiography. Standard echocardiography and color
      tissue Doppler imaging measures (early diastolic tissue velocity [Em], strain,
      and strain rate) were acquired at baseline and peak stress. The calibrated
      integrated backscatter was calculated from the at rest parasternal long-axis
      view. The longitudinal diastolic functional reserve index after exercise was
      defined as DeltaEm [1 - (1/Em(base))]. The clinical, anthropometric, and
      metabolic data were collected at rest and stress. Subclinical myocardial
      dysfunction at baseline (n = 24) was independently associated with weight (odds
      ratio [OR] 1.02, p = 0.04) and hemoglobin A1c (OR 1.36, p = 0.03). This group
      displayed an impaired exercise response that was independently associated with a
      reduced exercise capacity (OR 0.84, p = 0.034) and longitudinal diastolic
      functional reserve index (OR 0.69, p = 0.001). Inducible myocardial dysfunction
      (stress Em <-9.9 cm/s) was identified after exercise in 70 of the remaining 143
      subjects. This finding was associated with calibrated integrated backscatter (OR
      1.08, p = 0.04) and lower peak heart rate (OR 0.97, p = 0.002) but not metabolic
      control. The intensity of the metabolic derangement in patients with T2DM was
      associated with subclinical at rest myocardial dysfunction, but not with the
      myocardial exercise response. In conclusion, the association of an abnormal
      stress response with nonmetabolic factors, including backscatter and blunted peak
      heart rate, suggests potential roles for myocardial fibrosis and cardiac
      autonomic neuropathy in patients with nonischemic diabetic heart disease.

PMID- 21195377
TI  - Relation of obesity to recurrence rate and burden of atrial fibrillation.
AB  - Obesity is associated with new-onset atrial fibrillation (AF). However, the
      effect of obesity on AF recurrence or burden has not been studied. The aim of
      this study was to investigate the relation between AF recurrence, AF burden, and
      body mass index (BMI). A limited-access data set from the Atrial Fibrillation
      Follow-Up Investigation of Rhythm Management (AFFIRM) trial provided by the
      National Heart, Lung, and Blood Institute was used. Statistical analysis was done
      with a generalized linear mixed model. In 2,518 patients who had BMIs recorded,
      higher BMI was associated with a higher number of cardioversions (odds ratio [OR]
      1.017, 95% confidence interval [CI] 1.005 to 1.029 for a BMI increase of 1
      kg/m(2); OR 1.088, 95% CI 1.024 to 1.155 for a BMI increase of 5 kg/m(2); OR
      1.183, 95% CI 1.049 to 1.334 for a BMI increase of 10 kg/m(2); p = 0.006 for
      each). Increased BMI was also associated with a higher likelihood of being in AF
      on follow-up (OR 1.020, 95% CI 1.002 to 1.038 per 1 kg/m(2) increased BMI, p =
      0.0283; OR 1.104, 95% CI 1.011 to 1.205 per 5 kg/m(2) increased BMI, p = 0.0283;
      OR 1.218, 95% CI 1.021 to 1.452 per 10 kg/m(2) increased BMI, p = 0.0283). In a
      multivariate analysis, left atrial size but not BMI was an independent predictor
      of AF recurrence and AF burden. Because left atrial size was correlated with BMI,
      the effect of BMI on AF can be likely explained by greater left atrial size in
      subjects with higher BMIs. In conclusion, obesity is associated with a higher
      incidence of recurrence of AF and greater AF burden.

PMID- 21195378
TI  - Two-year safety and effectiveness of sirolimus-eluting stents (from a prospective
      registry).
AB  - Uncertainty exists about the long-term safety and efficacy outcomes of sirolimus
      eluting stents (SESs) in unselected patients. The present study was performed to
      evaluate the safety and efficacy of the SES in treatment of patients with
      coronary artery disease in an unselected population. Over a 2-year period, 1,504
      consecutive patients undergoing percutaneous coronary intervention with >=1 SES
      were enrolled. The primary end point was the occurrence of target vessel failure
      (TVF; a composite of cardiac death, myocardial infarction, or clinically driven
      target vessel revascularization). An independent clinical event committee
      adjudicated all adverse events up to 2-year follow-up. Dual antiplatelet therapy
      was recommended for >=1 year throughout the study period. Mean age was 65 +/- 11
      years; 75% were men, and 34% were diabetics. SESs were implanted for off-label
      indications in 86% of cases. TVF rates were 3.3%, 6.9%, 11.5%, and 15.5% at 30
      day, 6-month, 1-year, and 2-year follow-ups, respectively. The 2-year cumulative
      rate of definite/probable stent thrombosis was 0.9%; 0.2% was very late
      thrombosis, occurring from 1 year to 2 years. Patients off dual antiplatelet
      therapy at 6 months had a significantly increased rate of subsequent death from
      noncardiac causes. Patients off dual antiplatelet therapy at 1 year had a
      significantly decreased rate of subsequent clinically driven target lesion
      revascularization. In conclusion, use of SESs in unselected patients with
      coronary artery disease was associated with a low TVF rate at 2 years with an
      acceptable incidence of stent thrombosis.

PMID- 21195379
TI  - Clinically significant incidental findings among human immunodeficiency virus
      infected men during computed tomography for determination of coronary artery
      calcium.
AB  - Those infected with the human immunodeficiency virus (HIV) have a greater risk of
      cardiovascular disease and might undergo computed tomographic (CT) scans for
      early detection. Incidental findings on cardiac CT imaging are important
      components of the benefits and costs of testing. We determined the prevalence and
      factors associated with incidental findings on CT scans performed to screen for
      coronary artery calcium (CAC) among HIV-infected men. A clinically significant
      finding was defined as requiring additional workup or a medical referral. A total
      of 215 HIV-infected men were evaluated. Their median age was 43 years; 17% were
      current tobacco users; the median CD4 count was 580 cells/mm(3); and 83% were
      receiving antiretroviral medications. Also, 34% had a positive CAC score of >0.
      An incidental finding was noted among 93 participants (43%), with 36 (17%) having
      >=1 clinically significant finding. A total of 139 findings were noted, most
      commonly pulmonary nodules, followed by granulomas, scarring, and hilar
      adenopathy. Most of the incidental findings were stable on follow-up, and no
      malignancies were detected. The factors associated with the presence of an
      incidental finding in the multivariate model included increasing age (odds ratio
      1.6 per 10 years, p <0.01), positive CAC score (odds ratio 2.3, p <0.01), and
      current tobacco use (odds ratio 2.5, p = 0.02). In conclusion, incidental
      findings were common among HIV-infected men undergoing screening CT imaging for
      CAC determination. The incidental findings were more common among older patients
      and those with detectable CAC.

PMID- 21195380
TI  - Reperfusion by primary percutaneous coronary intervention in patients with ST
      segment elevation myocardial infarction within 12 to 24 hours of the onset of
      symptoms (from a prospective national observational study [PL-ACS]).
AB  - The aim of the present study was to investigate whether reperfusion by primary
      percutaneous coronary intervention (PCI) improves 12-month survival in late
      presenters with ST-segment elevation myocardial infarction (STEMI). We analyzed
      2,036 patients with STEMI presenting 12 to 24 hours from onset of symptoms,
      without cardiogenic shock or pulmonary edema and not reperfused by thrombolysis,
      of 23,517 patients with STEMI enrolled in the Polish Registry of Acute Coronary
      Syndromes from June 2005 to August 2006. An invasive approach was chosen in 910
      (44.7%) of late presenters and 92% of them underwent reperfusion by PCI. Patients
      with an invasive approach had lower mortality after 12 months than patients with
      a conservative approach (9.3% vs 17.9%, p <0.0001). The benefit of an invasive
      approach was also observed after multivariate adjustment with a relative risk
      0.73 for 12-month mortality (95% confidence interval 0.56 to 0.96) and in a
      subpopulation of patients selected by a propensity-score matching procedure with
      an adjusted relative risk 0.73 for 12-month mortality (0.58 to 0.99). In
      conclusion, almost 1/2 of late presenters with STEMI were considered eligible for
      reperfusion by primary PCI. These patients had a lower 12-month mortality rate
      than they would have had if they had been treated conservatively, which supports
      the idea of late reperfusion in STEMI. However, whether all late presenters with
      STEMI should be treated invasively remains unanswered. Nevertheless, until a
      randomized trial is undertaken, late presenters with STEMI could be considered
      for reperfusion by primary PCI.

PMID- 21195381
TI  - Perinatal high reliability.
AB  - Perinatal high reliability is achievable with principles of high reliability
      organizations. Key organizational, leadership, and clinical characteristics that
      are essential for developing and sustaining a highly reliable perinatal unit are
      presented. Interdisciplinary collaboration and commitment to safe care that are
      founded on standardization are the hallmarks of perinatal high reliability.

PMID- 21195382
TI  - Are antibiotics necessary after 48 hours of improvement in infected/septic
      abortions? A randomized controlled trial followed by a cohort study.
AB  - OBJECTIVE: We sought to investigate whether oral antibiotics are necessary, after
      48 hours of clinical improvement, in uncomplicated septic abortion. STUDY DESIGN:
      In a randomized double-blind clinical trial, 56 women with uncomplicated septic
      abortion were treated with intravenous antibiotics, followed by uterine
      evacuation. On hospital discharge (day 1), patients were randomized to receive
      either oral doxycycline plus metronidazole or placebo, until completing 10 days
      of treatment. Clinical cure was defined by the absence of fever (<37.7 degrees
      C), reduced vaginal bleeding, and minimal or no pelvic pain. RESULTS: Cure was
      observed in all 56 patients. The institutional review board stopped the treatment
      arm as it was adding risk with no further benefit to the patients. An
      observational cohort with additional 75 cases was followed up in the no treatment
      arm and no failure was identified (probability of an adverse event, 0%; 95%
      confidence interval, 0-0.03). CONCLUSION: After 48 hours of clinical improvement,
      antibiotics may not be necessary.

PMID- 21195383
TI  - Care for women with prior preterm birth.

PMID- 21195384
TI  - Staples vs subcuticular sutures for skin closure at cesarean delivery: a
      metaanalysis of randomized controlled trials.
AB  - Recently published randomized trials examining skin closure technique on
      postcesarean wound complications have produced conflicting results. We performed
      a metaanalysis of trials comparing staples and subcuticular sutures for skin
      closure at cesarean section (CS). Pooled outcome measures were calculated using
      random effects models. Primary outcomes were rates of wound dehiscence
      (separation) and a composite wound complication rate. Secondary outcomes were
      patient satisfaction, operating time, and postoperative pain. A total of 877
      women from 5 trials were included. Both wound separation (pooled odds ratio,
      4.01; P < .0001) and composite wound complication (pooled odds ratio, 2.11; P =
      .003) rates were higher with staples. The use of staples reduced operating time
      (weighted mean difference, -5.05 minutes; P = .021). Data on postoperative pain
      and patient satisfaction were insufficient for metaanalysis. Our findings suggest
      a possible benefit with subcuticular sutures compared to skin staples for skin
      closure at CS. However, the optimal skin closure technique at CS demands further
      study.

PMID- 21195386
TI  - Chlorzoxazone, an SK-type potassium channel activator used in humans, reduces
      excessive alcohol intake in rats.
AB  - BACKGROUND: Alcoholism imposes a tremendous social and economic burden. There are
      relatively few pharmacological treatments for alcoholism, with only moderate
      efficacy, and there is considerable interest in identifying additional
      therapeutic options. Alcohol exposure alters SK-type potassium channel (SK)
      function in limbic brain regions. Thus, positive SK modulators such as
      chlorzoxazone (CZX), a US Food and Drug Administration-approved centrally acting
      myorelaxant, might enhance SK function and decrease neuronal activity, resulting
      in reduced alcohol intake. METHODS: We examined whether CZX reduced alcohol
      consumption under two-bottle choice (20% alcohol and water) in rats with
      intermittent access to alcohol (IAA) or continuous access to alcohol (CAA). In
      addition, we used ex vivo electrophysiology to determine whether SK inhibition
      and activation can alter firing of nucleus accumbens (NAcb) core medium spiny
      neurons. RESULTS: Chlorzoxazone significantly and dose-dependently decreased
      alcohol but not water intake in IAA rats, with no effects in CAA rats.
      Chlorzoxazone also reduced alcohol preference in IAA but not CAA rats and reduced
      the tendency for rapid initial alcohol consumption in IAA rats. Chlorzoxazone
      reduction of IAA drinking was not explained by locomotor effects. Finally, NAcb
      core neurons ex vivo showed enhanced firing, reduced SK regulation of firing, and
      greater CZX inhibition of firing in IAA versus CAA rats. CONCLUSIONS: The potent
      CZX-induced reduction of excessive IAA alcohol intake, with no effect on the more
      moderate intake in CAA rats, might reflect the greater CZX reduction in IAA NAcb
      core firing observed ex vivo. Thus, CZX could represent a novel and immediately
      accessible pharmacotherapeutic intervention for human alcoholism.

PMID- 21195387
TI  - Neuroanatomic predictors to prodromal psychosis in velocardiofacial syndrome
      (22q11.2 deletion syndrome): a longitudinal study.
AB  - BACKGROUND: Up to 30% of young adults with velocardiofacial syndrome (VCFS;
      22q11.2 deletion syndrome) develop schizophrenia or psychosis. Identifying the
      neuroanatomic trajectories that increase risk for psychosis in youth with this
      genetic disorder is of great interest. METHODS: We acquired high-resolution
      anatomic magnetic resonance images and measures of psychiatric function on 72
      youth with VCFS, 26 unaffected siblings, and 24 age-matched community control
      subjects at two time points: between late childhood (mean age 11.9 years) and mid
      adolescence (mean age 15.1 years). RESULTS: With the exception of cranial gray
      matter and orbitofrontal prefrontal cortex, neuroanatomic trajectories in youth
      with VCFS were comparable to unaffected siblings and community control subjects
      during this developmental window. However, in youth with VCFS, longitudinal
      decreases in the volumes of cranial gray and white matter, prefrontal cortex,
      mesial temporal lobe, and cerebellum were associated with increased combined
      prodromal symptoms at Time 2. In contrast, only decreases in temporal lobe gray
      matter volumes (p < .002) and verbal IQ (p < .002) predicted specifically to
      positive prodromal symptoms of psychosis at Time 2. CONCLUSIONS: These findings
      are in line with studies of non-VCFS individuals at risk for schizophrenia and
      suggest that early decrements in temporal lobe gray matter may be predictive of
      increased risk of prodromal psychotic symptoms in youth with VCFS.

PMID- 21195389
TI  - Prevalence and perceived health associated with insomnia based on DSM-IV-TR;
      International Statistical Classification of Diseases and Related Health Problems,
      Tenth Revision; and Research Diagnostic Criteria/International Classification of
      Sleep Disorders, Second Edition criteria: results from the America Insomnia
      Survey.
AB  - BACKGROUND: Although several diagnostic systems define insomnia, little is known
      about the implications of using one versus another of them. METHODS: The America
      Insomnia Survey, an epidemiological survey of managed health care plan
      subscribers (n = 10,094), assessed insomnia with the Brief Insomnia
      Questionnaire, a clinically validated scale generating diagnoses according to DSM
      IV-TR; International Statistical Classification of Diseases, Tenth Revision (ICD
      10); and Research Diagnostic Criteria/International Classification of Sleep
      Disorders, Second Edition (RDC/ICSD-2) criteria. Regression analysis examines
      associations of insomnia according to the different systems with summary 12-item
      Short-Form Health Survey scales of perceived health and health utility. RESULTS:
      Insomnia prevalence estimates varied widely, from 22.1% for DSM-IV-TR to 3.9% for
      ICD-10 criteria. Although ICD insomnia was associated with significantly worse
      perceived health than DSM or RDC/ICSD insomnia, DSM-only cases also had
      significant decrements in perceived health. Because of its low prevalence, 66% of
      the population-level health disutility associated with overall insomnia and 84%
      of clinically relevant cases of overall insomnia were missed by ICD criteria.
      CONCLUSIONS: Insomnia is highly prevalent and associated with substantial
      decrements in perceived health. Although ICD criteria define a narrower and more
      severe subset of cases than DSM criteria, the fact that most health disutility
      associated with insomnia is missed by ICD criteria, while RDC/ICSD-only cases do
      not have significant decrements in perceived health, supports use of the broader
      DSM criteria.

PMID- 21195388
TI  - Aberrant striatal functional connectivity in children with autism.
AB  - BACKGROUND: Models of autism spectrum disorders (ASD) as neural disconnection
      syndromes have been predominantly supported by examinations of abnormalities in
      corticocortical networks in adults with autism. A broader body of research
      implicates subcortical structures, particularly the striatum, in the
      physiopathology of autism. Resting state functional magnetic resonance imaging
      has revealed detailed maps of striatal circuitry in healthy and psychiatric
      populations and vividly captured maturational changes in striatal circuitry
      during typical development. METHODS: Using resting state functional magnetic
      resonance imaging, we examined striatal functional connectivity (FC) in 20
      children with ASD and 20 typically developing children between the ages of 7.6
      and 13.5 years. Whole-brain voxelwise statistical maps quantified within-group
      striatal FC and between-group differences for three caudate and three putamen
      seeds for each hemisphere. RESULTS: Children with ASD mostly exhibited prominent
      patterns of ectopic striatal FC (i.e., functional connectivity present in ASD but
      not in typically developing children), with increased functional connectivity
      between nearly all striatal subregions and heteromodal associative and limbic
      cortex previously implicated in the physiopathology of ASD (e.g., insular and
      right superior temporal gyrus). Additionally, we found striatal functional
      hyperconnectivity with the pons, thus expanding the scope of functional
      alterations implicated in ASD. Secondary analyses revealed ASD-related
      hyperconnectivity between the pons and insula cortex. CONCLUSIONS: Examination of
      FC of striatal networks in children with ASD revealed abnormalities in circuits
      involving early developing areas, such as the brainstem and insula, with a
      pattern of increased FC in ectopic circuits that likely reflects developmental
      derangement rather than immaturity of functional circuits.

PMID- 21195390
TI  - Effect of chronic antipsychotic treatment on brain structure: a serial magnetic
      resonance imaging study with ex vivo and postmortem confirmation.
AB  - BACKGROUND: There is increasing evidence that antipsychotic (APD) may affect
      brain structure directly. To examine this, we developed a rodent model that uses
      clinically relevant doses and serial magnetic resonance imaging (MRI), followed
      by postmortem histopathological analysis to study the effects of APD on brain
      structures. METHODS: Antipsychotic , haloperidol, and olanzapine were
      continuously administered to rats via osmotic minipumps to maintain clinic-like
      steady state levels for 8 weeks. Longitudinal in vivo MRI scanning (T2-weighted)
      was carried out at baseline, 4 weeks, and 8 weeks, after which animals were
      perfused and their brains preserved for ex vivo MRI scanning. Region of interest
      analyses were performed on magnetic resonance images (both in vivo as well as ex
      vivo) along with postmortem stereology using the Cavalieri estimator probe.
      RESULTS: Chronic (8 weeks) exposure to both haloperidol and olanzapine resulted
      in significant decreases in whole-brain volume (6% to 8%) compared with vehicle
      treated control subjects, driven mainly by a decrease in frontal cerebral cortex
      volume (8% to 12%). Hippocampal, corpus striatum, lateral ventricles, and corpus
      callosum volumes were not significantly different from control subjects,
      suggesting a differential effect of APD on the cortex. These results were
      corroborated by ex vivo MRI scans and decreased cortical volume was confirmed
      postmortem by stereology. CONCLUSIONS: This is the first systematic whole-brain
      MRI study of the effects of APD, which highlights significant effects on the
      cortex. Although caution needs to be exerted when extrapolating results from
      animals to patients, the approach provides a tractable method for linking in vivo
      MRI findings to their histopathological origins.

PMID- 21195391
TI  - Association of reelin (RELN) single nucleotide polymorphism rs7341475 with
      prepulse inhibition in the Jewish Israeli population.

PMID- 21195394
TI  - [Hyaluronic acid breast injections: difficulties for mammographic monitoring].

PMID- 21195392
TI  - Neuronal correlates of cognitive reappraisal in borderline patients with
      affective instability.
AB  - BACKGROUND: Borderline personality disorder has been characterized by enhanced
      emotional reactivity and deficient emotion regulation in behavioral and
      functional imaging studies. We aimed to validate patients' difficulties in the
      cognitive regulation of negative emotions and investigated if emotion regulation
      deficits are restricted to the decrease of negative emotions. A cognitive
      reappraisal paradigm was used and hence a regulation strategy that is typically
      applied in cognitive-behavioral therapy. METHODS: Fifteen unmedicated female
      borderline patients with affective instability and 15 healthy female control
      subjects underwent functional magnetic resonance imaging during a delayed
      reappraisal paradigm. Hemodynamic responses were measured in response to aversive
      pictures in an initial viewing phase and a subsequent reappraisal phase with
      three different conditions: decreasing, increasing, and maintaining the initial
      emotional reaction. RESULTS: Patients demonstrated enhanced activation of left
      amygdala and right insula during the initial viewing of aversive stimuli. During
      attempting to decrease the initial emotional reaction, patients showed attenuated
      activation of the left orbitofrontal cortex and increased activation of the
      bilateral insula. The attempt to increase negative emotions resulted in enhanced
      activity in amygdala and insula, whereas no group differences were found.
      CONCLUSIONS: The results point to the role of two distinguishable processes of
      emotional difficulties in borderline personality disorder: enhanced emotional
      reactivity as well as deficits of voluntarily decreasing aversive emotions by
      means of cognitive reappraisal. The results suggest the neuronal substrate of
      deficits in explicit emotion regulation in the orbitofrontal cortex, which is in
      line with previous findings of a dysfunctional prefrontal network in borderline
      personality disorder.

PMID- 21195395
TI  - Gender differences in the perceived self-efficacy of safer HIV practices among
      polydrug abusers in Taiwan.
AB  - Studies have documented that the perceived self-efficacy of attempts to engage in
      safer behavior is critical for the prevention of blood-borne diseases, including
      hepatitis C and HIV. The aim of this study was to examine gender differences in
      the perceived self-efficacy of safer HIV-related behavior among heroin and
      amphetamine abusers. Of the eligible participants from Taiwan prisons, 1622
      polydrug users voluntarily agreed to complete a questionnaire regarding HIV
      risks. Participants had to be polydrug abusers (amphetamines and heroin), 18
      years or older, sexually experienced, and literate. The questionnaire addressed
      background information, drug abuse, sexual behavior, and perceived self-efficacy
      in drug- and sex-related HIV risk situations. Twenty-four percent of respondents
      were HIV positive. Compared to men, women started illicit drug use at a younger
      age and were less likely to share syringes. Women also tended to have their first
      sexual coitus at an older age and were less likely to use a condom in their last
      sexual encounter. Men were more likely to have multiple sexual partners in the
      past 6 months. Results from a multinomial logistic regression indicate that
      gender, age, their interaction, age of first sexual encounter, HIV knowledge,
      condom use at last sexual encounter, and multiple sexual partners were associated
      with perceived self-efficacy of condom use. Results also show that gender, HIV
      serostatus, HIV knowledge, condom use at last sexual encounter, and sharing
      needles at last injection were associated with perceived self-efficacy in not
      sharing needles. The findings provide evidence for gender differences among
      polydrug abusers in Taiwan regarding perceived self-efficacy in adopting HIV
      prevention practices. Findings also provide evidence that knowledge about HIV
      transmission is related to perceived self-efficacy in promoting safe behavior. To
      raise polydrug abusers' perceived self-efficacy, gender and HIV/AIDS education
      must be taken into consideration in counseling and/or public health education
      related to HIV prevention for drug abusers.

PMID- 21195397
TI  - Pregnancy in patient with Swyer syndrome.
AB  - OBJECTIVE: To report a case of successful pregnancy and delivery after IVF and ET
      in a patient with Swyer syndrome. DESIGN: Case report. SETTING: Unit of Assisted
      Reproduction, Gynecology and Obstetrics Institute, University of Belgrade.
      PATIENT(S): A 30-year-old patient with 46,XY gonadal dysgenesis. INTERVENTION(S):
      Chromosomal analysis, diagnostic laparoscopy, IVF using donor oocytes, ET, and
      cesarean delivery. MAIN OUTCOME MEASURE(S): Successful pregnancy and live birth.
      RESULT(S): Successful treatment, pregnancy, and delivery. CONCLUSION(S): A
      patient with 46,XY gonadal dysgenesis in a donor oocyte program, can maintain a
      normal pregnancy and delivery.

PMID- 21195396
TI  - Cognition and nondysphoric depression among adoptees at high risk for
      psychopathology.
AB  - BACKGROUND: Association between poor cognition and symptom clusters including
      depressive ideation (eg, guilt) and vegetative symptoms in the absence of
      dysphoria (nondysphoric depression [NDD]) has been suggested in the elderly. The
      current study examined associations between NDD and premorbid and concurrent
      cognitive functioning in younger adults at high risk for psychopathology.
      Nondysphoric depression and depressed subjects were expected to show poorer
      premorbid and current cognition than nondepressed participants. METHOD: Subjects
      were adoptees enrolled in the Iowa Adoption Study [Yates W, Cadoret R, Troughton
      E. The Iowa adoption studies: methods and results. On the way to individuality:
      methodological issues in behavioral genetics. In: LaBuda M, Grigorenko E, (Eds),
      Editor. 1999, Commack (NY): Nova Science Publishers, Inc. p. 95-121].
      Nondysphoric depression subjects were compared with nondepressed comparison
      subjects and with subjects with dysphoric depression (DD) on measures of
      premorbid cognition (estimated by standardized school achievement test scores)
      and concurrent cognition (intelligence, attention, memory, and executive
      abilities). RESULTS: Nondysphoric depression and DD showed lower premorbid
      cognition and executive functioning, whereas DD showed lower verbal and
      performance IQ compared to nondepressed subjects. The size of the comparison
      between NDD and nondepressed subjects for premorbid cognition was double that
      between DD and nondepressed subjects. No significant differences in cognition
      were found between NDD and DD. These effects were no longer significant after
      controlling for premorbid cognition. CONCLUSIONS: Poorer premorbid cognition and
      executive functions in NDD (and the absence of current cognitive differences
      compared with DD) suggest that NDD may be a condition of clinical interest.
      Because poor cognition is a known correlate of alexithymia, these results
      (including their magnitude) are consistent with the view that NDD may be a
      paradoxical presentation of depression in persons with limited ability to be
      aware and to verbally-report emotions.

PMID- 21195398
TI  - Oral nimodipine inhibits the ovarian cycle in mice.
AB  - Nimodipine, a calcium-channel blocker that can cross the blood-brain barrier, has
      been shown to inhibit pulsatile GnRH release in vitro. We now show that oral
      nimodipine can effectively inhibit the ovarian cycle in mice in a dose-related
      manner.

PMID- 21195399
TI  - Vitrification of mouse embryos with super-cooled air.
AB  - OBJECTIVE: To develop a closed vitrification device (i.e., one that requires no
      direct contact with liquid nitrogen) for successful cryostorage of embryos.
      DESIGN: Prospective laboratory research study. SETTING: University-based research
      laboratory. ANIMAL(S): F1 mice and mouse embryos. INTERVENTION(S): Mouse embryos
      were vitrified using two methods and compared with nonvitrified controls. Embryos
      were vitrified on a device by either [1] presealing it within a straw before
      plunging into liquid nitrogen or [2] placing the straw into liquid nitrogen so
      that the air inside the straw is super-cooled before inserting the device holding
      the embryos. MAIN OUTCOME MEASURE(S): Survival, subsequent embryo development,
      and cell number were determined. Embryos were also cryopreserved for 12 months to
      assess long-term storage. Synchronized ETs were performed to compare viability
      with nonvitrified control embryos. RESULT(S): All embryos survived with both
      techniques. Day-4 and -5 embryo development was comparable between the two
      vitrification methods. Use of the presealing method resulted in a significantly
      lower mean cell number than the postsealing method and control. Long-term storage
      did not affect subsequent embryo development or cell number. The implantation and
      fetal development rates of embryos vitrified with super-cooled air were
      comparable to those for nonvitrified control embryos. CONCLUSION(S): These data
      demonstrate that a closed vitrification device (Rapid-i), which does not require
      direct liquid nitrogen contact for vitrification, is appropriate for
      vitrification and long-term storage of mouse embryos.

PMID- 21195400
TI  - Comparative outcomes of hysteroscopic examinations performed after uterine artery
      embolization or laparoscopic uterine artery occlusion to treat leiomyomas.
AB  - Hysteroscopic examination of the uterine cavity revealed that patients previously
      treated for intramural myoma(s) by uterine artery embolization had a
      significantly higher incidence of abnormal findings compared with patients
      treated by laparoscopic occlusion of uterine arteries (59.5% vs. 2.7%). In
      particular, there was a higher incidence of necrosis in the uterine cavity of
      patients subjected to uterine artery embolization (43.2%) compared with patients
      after surgical uterine artery occlusion (2.7%).

PMID- 21195401
TI  - Women, weight, and fertility: the effect of body mass index on the outcome of
      superovulation/intrauterine insemination cycles.
AB  - OBJECTIVE: To determine the fecundity of overweight and obese infertile women
      treated with gonadotropins and undergoing intrauterine insemination (IUI).
      DESIGN: Retrospective study. SETTING: Academic infertility clinic. PATIENT(S):
      Four hundred seventy-seven women undergoing 1,189 ovulation induction (OI)/IUI
      cycles stratified by body mass index (BMI). INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): BMI groups were compared regarding the following: gonadotropin dose,
      duration of treatment, peak E(2), number of follicles (total, large, and medium
      size), E(2)/follicle, endometrial thickness, spontaneous abortion, and clinical
      and multiple pregnancy rates. RESULT(S): There was a significant trend toward
      higher medication requirements and lower E(2) levels with increasing BMI. BMI was
      inversely associated with [1] the E(2) level per produced preovulatory follicle
      and [2] the number of medium-size follicles. Furthermore, BMI was inversely
      associated with the number of medium, large, and total follicles divided by total
      FSH dose, suggesting that women with a higher BMI develop a lower number of
      medium and/or large follicles at a given total FSH dose. BMI was positively
      associated with endometrial thickness, and endometrial thickness was positively
      associated with pregnancy. Mean number of cycles required to conceive, clinical
      pregnancy, and spontaneous abortion rates did not differ significantly among the
      different BMI categories. CONCLUSION(S): Obese women require higher doses of
      medication and produce fewer follicles for a given dose, but once medication and
      response are adjusted to overcome the weight effect, the success of the treatment
      cycle is comparable to that of normal weight women.

PMID- 21195402
TI  - The effect of infertility and assisted reproduction on first-trimester placental
      and fetal development.
AB  - Our investigation of differences in first-trimester placentation and/or fetal
      biometry in pregnancies conceived spontaneously compared with those conceived
      through fertility treatment, and comparing less invasive fertility treatment with
      in vitro fertilization found no statistically significant difference in first
      trimester abnormal placentation or fetal growth between pregnancies conceived
      spontaneously and those conceived through fertility treatment, or between the in
      vivo and in vitro subgroups.

PMID- 21195403
TI  - Endoscopic creation of a gastrogastric conduit for reversal of gastric bypass.

PMID- 21195404
TI  - EUS-guided choledochoantrostomy: an alternative for biliary drainage in
      unresectable pancreatic cancer with duodenal invasion.

PMID- 21195405
TI  - Schistosoma japonicum showing flat colon polyp appearance.

PMID- 21195406
TI  - Onset and clinical course of bleeding and perforation after outpatient
      colonoscopy: a population-based study.
AB  - BACKGROUND: Endoscopists are advised to measure and report their rates of
      colonoscopy-associated perforation and bleeding. However, evidence from
      population-based studies is lacking on the time period over which monitoring is
      needed to detect these adverse events. OBJECTIVE: To determine the time course of
      perforation or bleeding requiring hospital admission within 30 days after
      outpatient colonoscopy. DESIGN: Population-based cohort study. SETTING: Ontario,
      Canada. PATIENTS AND INTERVENTIONS: Men and women, 50 to 75 years old who
      underwent an outpatient colonoscopy during the period from April 1, 2002 to March
      31, 2003. MAIN OUTCOME MEASUREMENTS: Hospitalization for colonoscopy-related
      perforation or bleeding within 30 days after the procedure. RESULTS: We
      identified 67,632 patients who had an outpatient colonoscopy, of whom 37 were
      admitted for hospitalization with perforation and 83 with bleeding within 30 days
      after the procedure. For those with a perforation, 34 of 37 (92%) were admitted
      within 2 days and all within 5 days. For those with bleeding, 30 of 83 (36%) were
      admitted within 2 days and 80 of 83 (96%) within 14 days. LIMITATIONS: Lack of
      information on medication use. CONCLUSIONS: After outpatient colonoscopy, use of
      a 14-day time period for reporting would capture all perforations and the
      majority (96%) of bleeds requiring hospital admission.

PMID- 21195407
TI  - Stone formation on bile duct stent remnant: stent gone bad!

PMID- 21195408
TI  - Successful treatment of a large hyperplastic polyp in the jejunum by using single
      balloon enteroscopy.

PMID- 21195409
TI  - GI involvement of sigmoid mucosal erosion in a 13-year-old girl with microscopic
      polyangiitis.

PMID- 21195410
TI  - Suitable hand dressings in children.

PMID- 21195411
TI  - Preparation of the monomers of gingerols and 6-shogaol by flash high speed
      counter-current chromatography.
AB  - The flash high speed counter-current chromatographic (FHSCCC) separation of
      gingerols and 6-shogaol was performed on a HSCCC instrument equipped with a 1200
      ml column (5 mm tubing i.d.) at a flow rate of 25 ml/min. The performance met the
      FHSCCC feature that the flow rate of mobile phase (ml) is equal to or greater
      than the square of the diameter of the column tubing (mm). The separation
      employed the upper phase of stationary phase of the n-hexane-ethyl acetate
      methanol-water (3:2:2:3, v/v) as the stationary phase. A stepwise elution was
      performed by eluting with the lower phase of n-hexane-ethyl acetate-methanol
      water (3:2:2:3, v/v) for first 90 min and the lower phase of the n-hexane-ethyl
      acetate-methanol-water (3:2:6:5, v/v) for the second 90 min. In each separation 5
      g of the ethyl acetate extract of rhizomes of ginger was loaded, yielding 1.96 g
      of 6-gingerol (98.3%), 0.33 g of 8-gingerol (97.8%), 0.64 g of 6-shogaol (98.8%)
      and 0.57 g of 10-gingerol (98.2%). The separation can be expected to scale up to
      industrial separation.

PMID- 21195412
TI  - Comparison of Dorris-Gray and Schultz methods for the calculation of surface
      dispersive free energy by inverse gas chromatography.
AB  - Inverse gas chromatography (IGC) is an important technique for the
      characterization of surface properties of solid materials. A standard method of
      surface characterization is that the surface dispersive free energy of the solid
      stationary phase is firstly determined by using a series of linear alkane liquids
      as molecular probes, and then the acid-base parameters are calculated from the
      dispersive parameters. However, for the calculation of surface dispersive free
      energy, generally, two different methods are used, which are Dorris-Gray method
      and Schultz method. In this paper, the results calculated from Dorris-Gray method
      and Schultz method are compared through calculating their ratio with their basic
      equations and parameters. It can be concluded that the dispersive parameters
      calculated with Dorris-Gray method will always be larger than the data calculated
      with Schultz method. When the measuring temperature increases, the ratio
      increases large. Compared with the parameters in solvents handbook, it seems that
      the traditional surface free energy parameters of n-alkanes listed in the papers
      using Schultz method are not enough accurate, which can be proved with a
      published IGC experimental result.

PMID- 21195413
TI  - Investigating comprehensive two-dimensional gas chromatography conditions to
      optimize the separation of oxygenated compounds in a direct coal liquefaction
      middle distillate.
AB  - Considering the global energetic context, diversifying fuels is of growing
      importance and many new alternatives are promising. Coal liquefaction products
      definitely appear among the new generation substitutes. These product's
      characteristics are very far from fuel specifications as they are mainly composed
      of naphthenes, aromatics, polycondensed naphthenic and aromatic structures and
      heteroatomic compounds (nitrogen and oxygen), with a very low paraffin content.
      Identification and quantification of oxygen-containing species in coal-derived
      liquids are of considerable importance to understand their behaviors in further
      processing. However, these species have not been characterized as fully as the
      predominant hydrocarbon components. Literature shows that these compounds consist
      mainly in alkylated phenolic and furanic structures. Therefore, comprehensive two
      dimensional gas chromatography has been investigated to provide enhanced
      molecular characterization of these complex samples. Several different
      configurations involving innovative column configurations were tested. Each of
      them was optimized by testing different column lengths, modulation periods, and
      oven conditions. A comparison of the contribution of each column configuration
      was carried out regarding four main criteria: individual separation of
      oxygenates, group type separation, resolution, and space occupation. One of them
      enabled an outstanding separation of paraffins, naphthenes, monoaromatics,
      diaromatics and targeted O-compounds in a direct coal liquefaction product. It
      was therefore subjected to further experimentations using a time-of-flight mass
      spectrometer to validate the identification and unravel more than fifty
      oxygenated molecular structures. A group-type quantification was also established
      for four column arrangements and gives the distribution of paraffins, naphthenes
      and aromatics. It can be concluded from this study that a non-orthogonal
      arrangement involving a highly polar column in the first dimension was the most
      adapted one.

PMID- 21195414
TI  - Relationship between circulating platelet counts and ductus arteriosus patency
      after indomethacin treatment.
AB  - OBJECTIVE: To determine whether low platelet counts are related to the incidence
      of patent ductus arteriosus (PDA) after indomethacin treatment in preterm human
      infants. STUDY DESIGN: Multivariable logistic regression modeling was used for a
      cohort of 497 infants, who received indomethacin (within 15 hours of birth).
      RESULTS: Platelet counts were not related to the incidence of permanent closure
      after indomethacin constriction. There was a relationship between platelet counts
      and the initial degree of constriction; however, this relationship appeared to be
      primarily influenced by the high end of the platelet distribution curve. PDA
      incidence was similar in infants with platelet counts < 50 * 109/L and those with
      platelet counts above this range. Only when platelet counts were consistently
      >230 *109/L was there a decrease in PDA incidence. CONCLUSION: In contrast to the
      evidence in mice, low circulating platelet counts do not affect permanent ductus
      closure (or ductus reopening) in human preterm infants.

PMID- 21195415
TI  - Management and outcomes in pediatric patients presenting with acute fulminant
      myocarditis.
AB  - OBJECTIVE: To investigate factors associated with mechanical circulatory support
      and survival in patients with acute fulminant myocarditis (AFM). STUDY DESIGN:
      Retrospective cohort of AFM patients admitted to the cardiac intensive care unit
      during 1996-2008. AFM was defined as distinct onset of symptoms <=14 days before
      admission, rapid-onset cardiogenic shock, and normal left ventricular size.
      Demographic and physiological variables were compared between patients treated
      with extracorporeal membrane oxygenation (ECMO) and those who were not and
      between survivors and nonsurvivors. RESULTS: Twenty patients (median age 12.7
      years) met inclusion criteria. Seventeen patients (85%) survived to hospital
      discharge. One underwent heart transplantation. Ten (50%) patients required ECMO,
      and 7 (70%) of these survived. On admission, patients requiring ECMO had elevated
      lactate (9 vs 1 mmol/L), creatinine (0.8 vs 0.6 mg/dL), and aspartate
      aminotransferase (256 vs 35 IU/L) (all P < .05) and a trend towards increased
      incidence of dysrhythmias (80% vs 30%, P = .07). During hospitalization, non
      survivors had higher peak lactate (10 vs 3 mmol/L), creatinine (1.5 vs 0.8
      mg/dL), and aspartate aminotransferase (3007 vs 156 IU/L) (all P < .05) compared
      with survivors. CONCLUSIONS: Patients with AFM with end organ dysfunction or
      arrhythmias on admission may require mechanical circulatory support. The
      transplant-free survival rate in this critically ill cohort was excellent (80%).

PMID- 21195416
TI  - Diagnosis of diabetes using hemoglobin A1c: should recommendations in adults be
      extrapolated to adolescents?
AB  - OBJECTIVE: To compare test performance of hemoglobin A1c (HbA1c) for detecting
      diabetes mellitus/pre-diabetes for adolescents versus adults in the United
      States. STUDY DESIGN: Individuals were defined as having diabetes mellitus
      (fasting plasma glucose [FPG] >= 126 mg/dL; 2-hour plasma glucose (2-hr PG) >=
      200 mg/dL) or pre-diabetes (100 <= FPG < 126 mg/dL; 140 <= 2-hr PG < 200 mg/dL.
      HbA1c test performance was evaluated with receiver operator characteristic (ROC)
      analyses. RESULTS: Few adolescents had undiagnosed diabetes mellitus (n = 4).
      When assessing FPG to detect diabetes, an HbA1c of 6.5% had sensitivity rates of
      75.0% (30.1% to 95.4%) and 53.8% (47.4% to 60.0%) and specificity rates of 99.9%
      (99.5% to 100.0%) and 99.5% (99.3% to 99.6%) for adolescents and adults,
      respectively. Additionally, when assessing FPG to detect diabetes mellitus, an
      HbA1c of 5.7% had sensitivity rates of 5.0% (2.6% to 9.2%) and 23.1% (21.3% to
      25.0%) and specificity rates of 98.3% (97.2% to 98.9%) and 91.1% (90.3% to 91.9%)
      for adolescents and adults, respectively. ROC analyses suggested that HbA1c is a
      poorer predictor of diabetes mellitus (area under the curve, 0.88 versus 0.93)
      and pre-diabetes (FPG area under the curve 0.61 versus 0.74) for adolescents
      compared with adults. Performance was poor regardless of whether FPG or 2-hr PG
      measurements were used. CONCLUSIONS: Use of HbA1c for diagnosis of diabetes
      mellitus and pre-diabetes in adolescents may be premature, until information from
      more definitive studies is available.

PMID- 21195417
TI  - Decreased expression of mineralocorticoid receptor mRNA and its splice variants
      in postmortem brain regions of patients with major depressive disorder.
AB  - Appropriate signaling in the brain by the glucocorticoid receptor (GR) and
      mineralocorticoid receptor (MR) is critical in regulation of the hypothalamic
      pituitary-adrenal (HPA) axis, emotional arousal and cognitive performance. To
      date, few data exist on MR (and GR) expression in the brain of patients suffering
      from major depressive disorder (MDD). With the help of quantitative PCR we
      assessed MR and GR mRNA expression, including the splice variants MRalpha and
      MRbeta, in tissue samples from the hippocampus, amygdala, inferior frontal gyrus,
      cingulate gyrus and nucleus accumbens. Expression levels were compared between
      tissue samples from six MDD patients and six non-depressed subjects. Relative to
      total GR, total MR mRNA expression was higher in hippocampus and lower in the
      amygdala, inferior frontal gyrus and nucleus accumbens. Both MRalpha and MRbeta
      could be detected in all brain regions that were analyzed, although MRbeta
      expression was low. Significantly lower expression levels (30-50%) were detected
      for MR or GR in hippocampal, inferior frontal gyrus and cingulate gyrus tissue
      from MDD patients (p < .05), while no differences were found in the amygdala or
      nucleus accumbens. The data show that both MRalpha and MRbeta mRNA are expressed
      throughout the human limbic brain with highest expressions in the hippocampus. A
      decreased expression of corticosteroid receptors in specific brain regions of MDD
      patients could underlie HPA hyperactivity, mood and cognitive disturbances often
      observed in patients suffering from stress-related psychopathologies.

PMID- 21195418
TI  - The microstructure of white matter in male to female transsexuals before cross
      sex hormonal treatment. A DTI study.
AB  - BACKGROUND: Diffusion tensor imaging (DTI) has been shown to be sensitive in
      detecting white matter differences between sexes. Before cross-sex hormone
      treatment female to male transsexuals (FtM) differ from females but not from
      males in several brain fibers. The purpose of this paper is to investigate
      whether white matter patterns in male to female (MtF) transsexuals before
      commencing cross-sex hormone treatment are also more similar to those of their
      biological sex or whether they are more similar to those of their gender
      identity. METHOD: DTI was performed in 18 MtF transsexuals and 19 male and 19
      female controls scanned with a 3 T Trio Tim Magneton. Fractional anisotropy (FA)
      was performed on white matter of the whole brain, which was spatially analyzed
      using Tract-Based Spatial Statistics. RESULTS: MtF transsexuals differed from
      both male and female controls bilaterally in the superior longitudinal
      fasciculus, the right anterior cingulum, the right forceps minor, and the right
      corticospinal tract. CONCLUSIONS: Our results show that the white matter
      microstructure pattern in untreated MtF transsexuals falls halfway between the
      pattern of male and female controls. The nature of these differences suggests
      that some fasciculi do not complete the masculinization process in MtF
      transsexuals during brain development.

PMID- 21195419
TI  - Alternate day calorie restriction improves systemic inflammation in a mouse model
      of sepsis induced by cecal ligation and puncture.
AB  - BACKGROUND: Calorie restriction (CR) exerts cytoprotective effects by up
      regulating survival factors, such as mammalian target of rapamycin (mTOR),
      sirtuin, and peroxisome proliferator-activated receptor-gamma co-activator 1alpha
      (PGC-1alpha). These survival factors have well-established roles in attenuating
      the inflammatory response. However, it is unclear whether CR affects sepsis
      related inflammation. The purpose of this study was to determine whether CR
      affects sepsis-induced inflammation in a cecal ligation and puncture (CLP)
      induced mouse model of sepsis. METHODS: Male C57BL/6N mice underwent alternate
      day calorie restriction or normal feeding for 8 d before CLP-induced sepsis.
      After induction of sepsis, liver and lung histopathology and serum levels of
      cytokines and survival factors were assessed. RESULTS: Serum cytokine and high
      mobility group box protein 1 (HMGB1) levels were lower in animals that underwent
      alternate day calorie restriction compared with normally-fed mice after CLP.
      Alternate day calorie restriction also increased levels of sirtuin, PGC-1alpha,
      and mTOR. While 80% of mice in the CLP group died within 48 h after undergoing
      CLP, 50% of mice died in the ACR + CLP group (P < 0.05). CONCLUSION: Alternate
      day calorie restriction decreased mortality in a mouse model of sepsis. In
      addition to attenuated organ injury, a significant reduction in cytokine and
      HMGB1 levels was observed. These findings suggest that alternative day calorie
      restriction may reduce excessive inflammation.

PMID- 21195420
TI  - Immunohistochemical and molecular analysis of tyrosine kinase activity in desmoid
      tumors.
AB  - BACKGROUND: Optimal surgical and medical therapy for the treatment of desmoid
      tumors (DT) is still undefined. Partial response to tyrosine kinase inhibitors
      (TKI) has previously been described. Here, we examined the role of the tyrosine
      kinases c-Src and c-Kit in driving desmoid tumorigenesis. METHODS: Six
      consecutive DT and matched normal tissues were collected from the operating room.
      Tissues were embedded in paraffin for immunohistochemical analysis, and protein
      lysates were prepared for immunoblot and immunoprecipitation. RESULTS: We found
      increased levels of beta-catenin in five of six (83%) DT relative to matched
      normal tissue by immunoblot analysis. By immunohistochemistry, beta-catenin
      expression was also increased in DT and localized to the nucleus. In contrast, we
      observed variable levels of total and activated c-Src and c-Kit expression in DT
      compared with normal tissue. Finally, beta-catenin tyrosine phosphorylation (p-Y)
      among tumors was variably increased, despite the increased amount of total beta
      catenin in tumors. CONCLUSIONS: Our results suggest that c-Src and c-Kit activity
      in DT is variable, consistent with the heterogeneous nature of this disease.
      Clinical response to TKI in DT may be via alternative mechanisms unrelated to c
      Src or c-Kit activity. Further insight into DT biology will help identify novel
      drug regimens to limit the morbidity and mortality associated with this disease.

PMID- 21195421
TI  - Elevated catecholamines and hepatic artery vasospasm in porcine small-for-size
      liver graft.
AB  - BACKGROUND: Elevated levels of norepinephrine (NE) have been reported in
      recipients of small-for-size liver (SFS) grafts in the perioperative period. The
      aim of the study is to test the hypothesis that although circulating
      catecholamines are elevated in recipients of SFS grafts, they are not the primary
      agents responsible for the hepatic artery (HA) vasospasm. METHODS: Female porcine
      recipients receiving a 20% (n = 10) partial liver graft were compared with a
      control group, using 60% partial liver transplanted grafts (n = 9). Hepatic blood
      flow (PVF, HAF) and levels of plasma catecholamines (epinephrine and NE) were
      measured at designated time points through postoperative day (POD) 7.
      Phentolamine (PA), an alpha-adrenergic blocker, was administered at doses of 1 to
      112.5 ug/kg/min through an indwelling HA to the recipients of 20% group on POD1
      (n = 5). RESULTS: In the 20% group following reperfusion, HA vasospasm was found
      at 10, 60, and 90 min, and persisted on POD 3 and POD 7. Plasma NE levels
      increased after reperfusion in 20% and 60% groups and peaked at 6 h with 10- to
      13-fold increased levels compared with baseline. In the 20% group, NE levels
      remained elevated up to POD 7. PA infusion at low (1-10 ug/kg/min) and high (12.5
      112.5 ug/kg/min) doses did not reverse the reduced HAF observed in 20% group
      recipients. CONCLUSION: Elevated serum NE does not appear to be the primary
      factor mediating HA vasospasm in the porcine SFS graft.

PMID- 21195422
TI  - L1 is highly expressed in tumors of the nervous system: a study of over 8000
      human tissues.
AB  - BACKGROUND: L1 cell adhesion molecule (CD171) has been detected in different
      malignant tumors and is associated with unfavorable outcome. It thus represents a
      target for tumor diagnosis and therapy. In this study, we assessed L1 expression
      in more than 8000 normal human tissues and different types of tumors, both
      malignant and non-malignant, and neural and non-neural. MATERIALS AND METHODS:
      Tissue micro-arrays, including a multi-tumor-array of 128 different tumor types,
      up to 50 samples of each type (approximately 5500 different samples), arrays with
      approximately 3000 different prostate and 600 mesenchymal tumor samples, and a
      normal human tissue-array were analyzed by immunohistochemistry with a monoclonal
      antibody using immunoperoxidase staining. RESULTS: L1 expression was detected in
      tumors of neural and neural crest origin and other types of non-neural tumors,
      but not in those of epithelial origin. In normal human tissues, L1 was detected
      in skin basal cells and small blood vessels, most notably in the mature placenta
      and peripheral nerves. CONCLUSION: This first comprehensive study of the
      importance of L1 expression in human demonstrates strong L1 overexpression in
      tumors of neuroectodermal and neural crest origin and an expression in only very
      few normal human tissues. L1 thus is a potentially important therapeutic target,
      particularly with respect to malignant melanoma, gastrointestinal stromal tumor,
      neuroblastoma, and certain subtypes of non-neural tumors.

PMID- 21195423
TI  - Trans-iliac rat aorta stenting: a novel high throughput preclinical stent model
      for restenosis and thrombosis.
AB  - BACKGROUND: Currently, preclinical stent development requires elaborate large
      animal models, which are time consuming and expensive. We herein report a high
      throughput rat aorta stenting model which could provide a rapid and low-cost
      platform for preclinical stent development. METHODS: A total of 86 metal stents
      (316L stainless steel 13 mm, VasoTech, Inc.) coated with poly (D, L-lactide-co
      glycolide)/amorphous calcium phosphate (PLGA/ACP) copolymer were pre-mounted on
      1.5 mm * 15 mm balloon catheters and were implanted into aspirin treated Sprague
      Dawley rats (500-700 g) initially using either direct placement in the abdominal
      aorta (group A, n = 7) or a trans-iliac approach (cut-down, group B, n = 79). The
      surviving rats were sacrificed at 1, 2, 4, and 12 wk post-implantation and the
      stented arteries were analyzed histopathologically. RESULTS: Four rats died in
      group A and nine rats died in group B within 48 h post-stent implantation
      (mortality: 57% versus 11%, P < 0.05). All animals that died had stent
      thrombosis/paralysis with visible thrombus on necropsy. Histologically,
      neointimal growth peaked at approximately 4 wk post-implantation. CONCLUSION:
      This result suggests that human-sized stents can be successfully implanted into
      the rat aorta via iliac artery insertion with a significantly higher survival
      rate than trans-aorta implantation. The model system allows rapid (4-12 wk)
      assessment of stent biocompatibility with mortality/paralysis used as an
      indicator of stent thrombosis.

PMID- 21195424
TI  - Predicting the risk of anastomotic leakage in left-sided colorectal surgery using
      a colon leakage score.
AB  - BACKGROUND: Anastomotic leakage following colorectal surgery still occurs all too
      frequently, and this complication is difficult to predict. A nonfunctional stoma
      may reduce the risk of clinically relevant leaks but is overtreatment for most
      patients. More accurate assessments of the risk of anastomotic leakage would be
      very helpful in tailoring treatment in colorectal surgery. Therefore, a Colon
      Leakage Score (CLS) was developed and tested. MATERIAL AND METHODS: The CLS was
      developed based on information from the literature and expert opinions. It was
      tested in a retrospective cohort of consecutive patients undergoing left-sided
      colorectal surgery with primary anastomosis in a teaching hospital in The
      Netherlands. RESULTS: In the test cohort, 10 of 121 patients who were not treated
      with a nonfunctional stoma experienced anastomotic leakage. The mean CLS in the
      leakage group was 16 versus eight in the group that did not have a leak (P <
      0.01). Using receiver-operating characteristics, the area under the curve (AUC)
      showed that the CLS was a good predictor (AUC = 0.95, CI 0.89-1.00) of
      anastomotic leakage. Furthermore, logistic regression analysis with CLS as a
      predictor for anastomotic leakage showed an odds ratio of 1.74 (95% CI 1.32-2.28,
      P < 0.01). CONCLUSIONS: The CLS can predict the risk of anastomotic leakage
      following left-sided colorectal surgery. After further validation, this score may
      help the surgeon make a more individualized, safer decision regarding whether to
      perform an anastomosis or make a (nonfunctional) stoma.

PMID- 21195425
TI  - Circulating myeloid dendritic cells as prognostic factors in patients with
      pancreatic cancer who have undergone surgical resection.
AB  - OBJECTIVE: Pancreatic cancer is a malignant neoplasm with poor prognosis that
      might be associated with defective immune function. We aimed to determine the
      influence on survival of circulating myeloid dendritic cells (c-m-DCs),
      circulating lymphoid DCs (c-l-DCs), and DCs within the tumor tissue in patients
      with pancreatic cancer. PATIENTS AND METHODS: Between December 2001 and June
      2006, of a total of 110 patients with ductal adenocarcinoma of the pancreas, 42
      underwent pancreatectomy, and 68 had unresectable disease. Numbers of c-m-DCs and
      c-l-DCs were assessed by flow cytometry, and DCs in the tumor tissue by
      immunohistochemical staining with anti-fascin mAb. RESULTS: The percentage of the
      c-m-DCs subset in pancreatic cancer patients was significantly lower than in
      healthy volunteers, and the similar finding was observed between patients who
      underwent surgical resection and non-resection. Patients with a high percentage
      of c-m-DCs or with many DCs accumulated in the cancer tissue survived longer than
      patients with a low percentage or low number in peripheral blood or the tumor,
      respectively. Moreover, there was a positive correlation between c-m-DCs within
      peripheral blood mononuclear cells and the number of DCs per field in the cancer
      tissue. CONCLUSIONS: Preoperative c-m-DCs levels in the PBMC of patients with
      pancreatic cancer and DCs counts in the cancer tissue can be a prognostic factor
      after surgical resection. Modulating the distribution of DCs may be an effective
      therapy in pancreatic cancer patients with a dismal prognosis.

PMID- 21195426
TI  - Comparison of "open lung" modes with low tidal volumes in a porcine lung injury
      model.
AB  - BACKGROUND: Ventilator strategies that maintain an "open lung" have shown promise
      in treating hypoxemic patients. We compared three "open lung" strategies with
      standard of care low tidal volume ventilation and hypothesized that each would
      diminish physiologic and histopathologic evidence of ventilator induced lung
      injury (VILI). MATERIALS AND METHODS: Acute lung injury (ALI) was induced in 22
      pigs via 5% Tween and 30-min of injurious ventilation. Animals were separated
      into four groups: (1) low tidal volume ventilation (LowVt -6 mL/kg); (2) high
      frequency oscillatory ventilation (HFOV); (3) airway pressure release ventilation
      (APRV); or (4) recruitment and decremental positive-end expiratory pressure
      (PEEP) titration (RM+OP) and followed for 6 h. Lung and hemodynamic function was
      assessed on the half-hour. Bronchoalveolar lavage fluid (BALF) was analyzed for
      cytokines. Lung tissue was harvested for histologic analysis. RESULTS: APRV and
      HFOV increased PaO(2)/FiO(2) ratio and improved ventilation. APRV reduced BALF
      TNF-alpha and IL-8. HFOV caused an increase in airway hemorrhage. RM+OP decreased
      SvO(2), increased PaCO(2), with increased inflammation of lung tissue.
      CONCLUSION: None of the "open lung" techniques were definitively superior to
      LowVt with respect to VILI; however, APRV oxygenated and ventilated more
      effectively and reduced cytokine concentration compared with LowVt with nearly
      indistinguishable histopathology. These data suggest that APRV may be of
      potential benefit to critically ill patients but other "open lung" strategies may
      exacerbate injury.

PMID- 21195427
TI  - Noninvasive delayed limb ischemic preconditioning in rats increases antioxidant
      activities in cerebral tissue during severe ischemia-reperfusion injury.
AB  - BACKGROUND: To study the protection offered by noninvasive delayed limb ischemic
      preconditioning (NDLIP) against cerebral ischemia reperfusion (I/R) injury in
      rats. MATERIALS AND METHODS: Healthy male Wistar rats were randomly divided into
      four groups. The delayed protection offered by NDLIP was estimated in light of
      changes in the neural behavior marker and cerebral tissue antioxidative ability.
      Neurological functions were studied by observing neural behavior. Total
      superoxide dismutase (T-SOD), manganese-superoxide dismutase (Mn-SOD),
      glutathione peroxidase (GSH-PX), and xanthine oxidase (XOD) activity in cerebral
      tissue and malonaldehyde (MDA) content were detected using a spectrophotometer.
      Mn-SOD mRNA was measured by the reverse transcription polymerase chain reaction
      method. RESULTS: Cerebral infarct size was diminished in the early cerebral
      ischemia preconditioning (ECIP)+I/R and NDLIP+I/R groups compared with the I/R
      group (P < 0.05). The cortical and hippocampal antioxidant enzyme activity and Mn
      SOD expression were increased in the ECIP+I/R and NDLIP+I/R groups. In contrast,
      the cortical and hippocampal XOD activity and MDA content decreased in the
      ECIP+I/R and NDLIP+I/R groups. CONCLUSIONS: NDLIP decreased cerebral infarct
      size, increased cerebral antioxidative ability after I/R injury, and decreased
      peroxidative damage. The antioxidative protection offered by NDLIP was as
      effective as that offered by ECIP.

PMID- 21195428
TI  - Translating cancer genomes sequencing revolution into surgical oncology practice.
AB  - BACKGROUND: Ten years after the first complete human genome sequencing, next
      generation sequencing (NGS) technology has revolutionized genomics and biomedical
      research. Here we discuss potential emerging and future applications of NGS
      platforms and how cancer genome advances may change current surgical oncology
      practice. MATERIALS AND METHODS: Publications in PubMed with partial or complete
      human and cancer genome sequencing over the last decade have been retrieved and
      analyzed. Recently launched international large-scale consortiums for systematic
      study of causal (driver) mutations underlying common complex diseases such as
      cancer and more recent opinion articles by leading scientists have been
      considered to predict the prospects of integration genomics data into surgical
      oncology. RESULTS: Two dozen complete human genome sequences, and three full
      genome sequencing in three cancer patients have recently been published. These
      studies and other cancer genome systematic studies evaluating genomic
      rearrangements and copy-number changes consistently reveal that cancer initiation
      and metastasis are much more complex than we thought. This high complexity and
      widespread variability of cancer genes, mutations, and deregulated signaling
      pathways among patients with the same cancer type, tumor stage, and
      clinicopathologic features explains the limited effectiveness of currently used
      biologically targeted agents. CONCLUSIONS: Yet the impact of genomics explosion
      in surgical oncology is little. Nevertheless, "big" biology consortiums such as
      the International Cancer Genome Project and other systematic studies in the areas
      of genetics, genomics, and epigenetics are now providing in-depth understanding
      of cancer, and shape new more rational ways towards novel therapeutics for
      improving oncologic outcomes of millions of patients worldwide. At the beginning
      of the second post-genomic decade, an explosion in genomic technology has
      revolutionized biomedical sciences. The ability of latest DNA sequencing
      technology to identify, in an unprecedented level, causal mutations driving
      cancer initiation and metastasis raises significant expectations for improving
      oncologic outcomes. Which are the challenges and perspectives to translate this
      genomic revolution into a surgical oncology-changing era?

PMID- 21195429
TI  - Intrahepatic radiofrequency ablation versus electrochemical treatment ex vivo.
AB  - BACKGROUND: Radiofrequency ablation (RFA) and electrochemical treatment (ECT) are
      two methods of local liver tumor ablation. A reproducible perfusion model allowed
      us to compare these methods when applied in proximity to vascular structures.
      MATERIAL AND METHODS: In a porcine liver perfusion model, we used RFA (group A)
      and ECT (group B) to perform ablations under ultrasound guidance within 10 mm of
      a vessel and examined the induced necrosis macroscopically and histologically.
      RESULTS: We created 83 lesions (RFA: 59, ECT: 24) in 27 livers. In group A (mean
      liver weight: 2046 g), perfusion was macroscopically found to limit necrosis in
      52.5% of the procedures. Histology demonstrated the destruction of only 30.4% of
      the vessel walls within the ablation areas. In group B (mean liver weight: 1885
      g), we detected reproducible and sharply demarcated ablation areas both
      macroscopically and histologically. Necrosis was unaffected by nearby vessels. No
      viable cells were found perivascularly. Histology showed destruction of the
      vascular endothelium without any discontinuities. We measured pH values of 0.9
      (range: 0.6-1.8) at the anode and 12.2 (range: 11.4-12.6) at the cathode.
      Treatment time was 100 min when a charge of 300 coulombs was delivered.
      CONCLUSIONS: Electrochemical treatment is a method of ablation that creates
      reproducible and predictable volumes of necrosis. It produces sharply demarcated
      areas of complete necrosis also in perivascular sites. ECT, however, requires
      much longer treatment times than RFA. In our model, the effects of RFA were
      considerably limited by perfusion, which caused incomplete areas of necrosis in
      proximity to vessels.

PMID- 21195430
TI  - Alcoholic versus nonalcoholic cirrhosis in a randomized controlled trial of
      emergency therapy of bleeding varices.
AB  - BACKGROUND: It has been proposed that portal-systemic shunts be avoided in
      alcoholic cirrhotics because survival rate is allegedly lower in alcoholics than
      in nonalcoholics. We examined this issue in a randomized controlled trial.
      METHODS: Two hundred eleven unselected, consecutive patients with cirrhosis and
      bleeding esophageal varices were randomized to endoscopic sclerotherapy (EST) (n
      = 106) or emergency portacaval shunt (EPCS) (105). Treatment was initiated within
      8 h. EST failure was treated by rescue portacaval shunt (PCS). Ten-year follow-up
      was 96%. RESULTS: Results strongly favored EPCS over EST (P < 0.001). Among EPCS
      patients, 83% were alcoholic and 17% nonalcoholic. Outcomes were (1) permanent
      control of bleeding 100% versus 100%; (2) 5-y survival 71% versus 78%; (3)
      encephalopathy 14% versus 19%; (4) yearly charges $38,300 versus $43,000.
      CONCLUSIONS: EPCS results were similar in alcoholic and nonalcoholic cirrhotics.
      EPCS is an effective first line emergency treatment in all forms of cirrhosis,
      including alcoholic.

PMID- 21195431
TI  - A prospective case-control study of the local and systemic cytokine response
      after laparoscopic versus open colonic surgery.
AB  - BACKGROUND: There is a sequential, high concentration cytokine response after
      major abdominal surgery. The magnitude of this response has been directly linked
      to postoperative metabolic derangement, ileus, adhesions, and oncological
      outcomes. We aimed to compare the local and systemic cytokine response in
      laparoscopic and open colonic surgery and relate this to postoperative recovery
      parameters. METHODS: Using a prospectively collected patient database, we
      compared a Study Group (n = 50) of patients undergoing elective laparoscopic
      colonic resection with a Control Group (n = 25) of patients undergoing equivalent
      open colonic surgery within an ERAS program. Patients were matched for age,
      gender, BMI, ASA, Cr Possum, side of resection, diagnosis, and histologic stage.
      Plasma and peritoneal fluid concentrations of IL-6, IL-8, IL-10, and TNFalpha
      were measured at 20-24 h after surgery. The Surgical Recovery Score was
      determined pre-operatively and at 3, 7, 30, and 60 d postoperatively. All data
      were prospectively collected, and a priori definitions were used for discharge
      parameters, complications, and complication severity. RESULTS: Peritoneal fluid
      IL-6 concentration was lower after laparoscopic surgery. There were no
      significant differences in the other cytokines measured, or in any postoperative
      recovery outcomes. Significant correlations were found between cytokine levels
      and discharge criteria achievement, day stay, postoperative complications, and
      the Surgical Recovery Score. CONCLUSION: With the exception of a lower peritoneal
      IL-6 level, the systemic and peritoneal cytokine response at 20-24 h is similar
      after laparoscopic versus open colonic resection within an ERAS program, with
      corresponding equivalent rates of postoperative recovery.

PMID- 21195432
TI  - Polymorphisms in MMP-9 and TIMP-2 in Chinese patients with varicose veins.
AB  - BACKGROUND: Varicose veins (VVs), a common vascular disease, are functionally
      characterized by dilation and tortuosity and are widely prevalent in the adult
      population. The pathophysiology and molecular mechanism of VVs are still unclear.
      A genetic risk for VVs has been demonstrated, although no genetic variant
      pertaining to VVs has been identified. Matrix metalloproteinases (MMPs) and their
      endogenous tissue inhibitors (TIMPs), which can prevent excessive extracellular
      matrix (ECM) degradation, greatly impact vascular remodeling and may play a vital
      role in patients with VVs. We evaluated a potential association between
      polymorphisms in the promoters of MMP-9 and TIMP-2 and the risk for VVs in the
      Chinese population. MATERIALS AND METHODS: Genotyping of the promoter region
      polymorphisms -1562C/T in MMP-9 and -418G/C in TIMP-2 was performed with PCR and
      restriction fragment length polymorphism (PCR-RFLP) assays with a group of 60
      patients with VVs and 60 healthy controls. Purified PCR products were sequenced.
      RESULTS: A significant correlation was found between patients with VVs and
      controls at -1562C/T in MMP-9. The TIMP-2 gene polymorphism -418G/C was also
      associated with VVs. CONCLUSIONS: Our results suggest that polymorphisms in the
      promoter region of MMP-9 and TIMP-2 are associated with VVs in the Chinese
      population.

PMID- 21195433
TI  - Effect of choline-containing phospholipids on brain cholinergic transporters in
      the rat.
AB  - The influence of one week treatment with the choline-containing phospholipids
      cytidine-5'-diphosphocholine (CDP-choline) and choline alphoscerate (L-alpha
      glyceryl-phosphorylcholine) at choline-equivalent doses (CDP-choline: 325
      mg/kg/day; choline alphoscerate: 150 mg/kg/day) on vesicular acetylcholine
      transporter (VAChT), on choline transporter (CHT) and on acetylcholine (ACh)
      concentrations was investigated in rat frontal cortex, striatum and cerebellum.
      ACh was assayed by HPLC with electrochemical detection, VAChT by Western blot,
      ELISA and immunohistochemistry, CHT by Western blot and immunohistochemistry.
      After CDP-treatment, ACh levels were slightly increased in the frontal cortex,
      not substantially different in the striatum, and reduced significantly in the
      cerebellum compared to controls. Choline alphoscerate stimulated significantly
      the neurotransmitter concentration in the frontal cortex, however, the levels
      were similar to the controls in both the striatum and cerebellum. In comparison
      to the controls, VAChT expression following either CDP-choline or choline
      alphoscerate treatment, was enhanced greatly in the striatum and cerebellum.
      Also, ELISA measurements for VAChT showed significant increases in all choline
      alphoscerate treated brain areas. In contrast, in the CDP-choline treated rats
      the vesicular transporter amount was greater than the control only in the
      striatum. The cholinergic presynaptic transporters VAChT and CHT play a relevant
      role in sustaining new ACh synthesis and release. To sum up, CDP-choline and
      choline alphoscerate stimulated to a different extent the expression of VAChT and
      CHT primarily in a cognitive area such as frontal cortex. In the lack of novel
      therapeutic strategies, safe compounds developed since a long time such as the
      choline-containing phospholipids investigated would merit to be further
      investigated by new and adequate clinical studies. This for assessing their place
      if any in pharmacotherapy of dementia disorders characterized by diminished
      cholinergic tone.

PMID- 21195434
TI  - Distal motor axonal dysfunction in amyotrophic lateral sclerosis.
AB  - Nerve conduction slowing in amyotrophic lateral sclerosis (ALS) is usually caused
      by loss of fast motor axons. We studied the frequency, extent, and distribution
      of prominently prolonged distal motor latencies in ALS. We reviewed results of
      median, ulnar, and tibial nerve conduction studies in 91 patients with ALS, 24
      with lower motor neuron disorders, and 36 with axonal neuropathy. Coincidental
      carpal tunnel syndrome was found for 4 (4.4%) of the ALS patients who were
      excluded from analyses. Markedly prolonged distal latencies (>125% of the upper
      limit of normal) were found only in the median nerve of ALS patients (9%), and in
      none of the disease controls. Excitability studies suggested membrane
      depolarization in some ALS patients. Our results show that approximately 10% of
      ALS patients shows prominently prolonged median distal latency, which cannot be
      explained by axonal loss and carpal tunnel lesion. The distal nerve conduction
      slowing may partly be caused by membrane depolarization possibly due to motor
      neuronal degeneration in ALS. We suggest that recognition of the pattern of
      distal motor axonal dysfunction predominant in the median nerve is clinically
      important, and could provide additional insights into the pathophysiology of ALS.

PMID- 21195435
TI  - Large numbers of stroke physicians should be used to treat large numbers of
      stroke patients with IV rt-PA.
AB  - PURPOSE: Our aim was to investigate the relationship between number of stroke
      physicians (SPs) and number of patients treated with intravenous thrombolysis (IV
      rt-PA) per year. METHODS: Questionnaires about the infrastructure of acute stroke
      care including number of SPs and patients given IV rt-PA from October 2008 to
      September 2009 were sent to 3877 hospitals in Japan. We compared the number of
      SPs between: 1) hospitals not giving IV rt-PA for a year vs. hospitals giving IV
      rt-PA for >= 1 patient; 2) <= 5 vs. >5 patients; 3) <= 10 vs. >10 patients; and
      4) <= 25 vs. >25 patients. We established cut-off numbers of SPs administering IV
      rt-PA for >= 1, >5, >10, and >25 patients/hospital/year using a sensitivity
      specificity curve. RESULTS: Responses were received from 2488 of the 3877
      hospitals (64.2%), and 919 hospitals admitted acute stroke patients. Of these,
      385 hospitals were not administering IV rt-PA in that year, 250 hospitals gave IV
      rt-PA for 1-4 patients, 131 hospitals for 5-9 patients, 102 hospitals for 10-25
      patients, and 30 hospitals for >25 patients. Cut-off numbers of SPs per hospital
      were 1 doctor administering IV rt-PA for >= 1 patient/year (sensitivity, 83.8%;
      specificity, 84.5%), 2 doctors for >5 patients (sensitivity, 85.9%; specificity,
      74.1%), 3 doctors for >10 patients (sensitivity, 76.3%; specificity, 75.5%), and
      4 doctors for >25 patients (sensitivity, 86.2%; specificity, 78.5%). An
      independent factor for IV rt-PA with >25 patients was >= 4 SPs (odds ratio, 3.83;
      95% confidence interval, 1.17-12.63; p=0.027). CONCLUSIONS: Higher numbers of SPs
      should be associated with higher numbers of patients getting IV rt-PA.

PMID- 21195436
TI  - Microbial water quality of the Georgian coastal zone of the Black Sea.
AB  - From 2006 to 2008, microbial water quality was monitored along the Georgian coast
      of the Black Sea. Temperature, pH, salinity, and dissolved oxygen were measured,
      along with a variety of aquatic microbial parameters, including heterotrophic
      plate count (HPC), total culturable bacterial count (TCBC), and chlorophyll a
      (Chl-a) concentration. Total and fecal coliforms and total enterococci counts
      were recorded as indicators of fecal pollution. Vibrio bacteria, and Escherichia
      coli- and Vibrio-specific bacteriophages were isolated and enumerated to
      determine their relationships to standard marine pollution indicators. Persistent
      microbial pollution was observed, particularly in the summer months, with a
      higher rate of contamination in estuaries. Microbial indicators generally showed
      seasonal dependence, suggesting that temperature may influence bacterial dynamics
      in this environment. No correlation was apparent between fecal pollution
      indicators and physical-chemical and aquatic microbial parameters, although there
      were significant relationships amongst the indicators themselves, as well as with
      the prevalence of Vibrio bacteria and phage.

PMID- 21195437
TI  - Benthic macroinvertebrates as indicators of environmental deterioration in a
      large microtidal estuary.
AB  - This study tested the hypothesis that, during recent years, the benthic
      macroinvertebrate fauna of the large basin of the Swan-Canning Estuary has
      changed in ways consistent with deteriorating environmental conditions in that
      estuary. Between 1986/7 and 2003/4, the compositions of that fauna altered
      markedly at the species and even family levels. Thus, the densities and number of
      species of molluscs, and especially of crustaceans, which are particularly
      susceptible to environmental stress, declined, while those of the more tolerant
      polychaetes increased. However, taxonomic distinctness declined consistently only
      at one of the four widely-spaced sampling sites and the dispersion of samples did
      not differ markedly between periods, indicating that the benthic fauna has not
      undergone such extreme changes as in the nearby Peel-Harvey Estuary. It is thus
      proposed that benthic macroinvertebrates can act as important indicators of the
      severity of environmental degradation in microtidal estuaries in regions where
      such perturbations are increasing.

PMID- 21195438
TI  - The recurvatianes: a suite of oxygenated guaiane sesquiterpenes from Perezia
      recurvata.
AB  - Six guaiane sesquiterpenes recurvatiane A-F, including the previously known
      recurvatiane E and xanthomicrol, were isolated from the Andean Perezia recurvata
      and their structures determined by spectroscopic evidence. The absolute
      stereochemistry of recurvatiane A was established by derivatization with (R)- and
      (S)-alpha-methoxy-alpha-phenylacetic acids (MPA). The suite of guaiane-based
      metabolites here reported, which we have named recurvatianes A-F, provide an
      example of a pathway by which molecular diversity is generated by the occurrence
      of specific oxidation reactions in the late biosynthetic steps of the frame
      structure.

PMID- 21195439
TI  - Nitric oxide synthase expression in foetal placentas of cows with retained fetal
      membranes.
AB  - The objectives of this study were to investigate relationship of retained fetal
      membranes (RFM) to expression of NOS and NOS mRNA and to analyze
      pathohistological changes and the distribution of nitric oxide synthase (NOS) in
      foetal placentas of cows with RFM. Twenty cows were assigned to two groups, a
      control group (no retained fetal membranes, NRFM, n = 10) and a diseased group
      (RFM, n = 10). The endpoint method was used to detect the nitric oxide (NO)
      content and nitric oxide synthase (NOS) activity in foetal placental tissue fluid
      and the fluorescent quantitation PCR was used to measure the expression of NOS
      mRNA. Immunohistochemistry and hematoxylin-eosin staining were used to observe
      pathohistological changes. Tissue from RFM cows showed fibronecrosis of the
      chorionic villi, and a decreased number of trophoblastic cells. The majority of
      trophoblastic cells displayed vacuolar degeneration. Interstitium vessels were
      distended and congested. Expression of induced nitric oxide synthase (iNOS)
      protein and iNOS mRNA was significantly higher (P < 0.05) in the cytoplasm of
      placental villus trophoblastic cells in the RFM group. But expression of
      endothelial nitric oxide synthase (eNOS) protein and eNOS mRNA was significantly
      lower (P<0.05) in the RFM group. The NO content and NOS activity of cows with RFM
      were significantly higher (P < 0.05). A high expression of iNOS protein and iNOS
      mRNA in the cow foetal placenta could produce high content of NO, which might
      inhibit uterine contraction. So over expression of iNOS protein and iNOS mRNA
      might be an important agent of retained fetal membranes in cows, and it may be a
      potential diagnosis biomarker.

PMID- 21195440
TI  - [Peripheral neuropathies associated with hereditary cerebellar ataxias].
AB  - Inherited cerebellar ataxias constitute a complicated and heterogeneous group of
      neurodegenerative disorders affecting the cerebellum and/or spinocerebellar
      tract, spinal cord and peripheral nerves. A peripheral neuropathy is frequently
      seen in inherited cerebellar ataxias although it rarely reveals the disease.
      Moreover, the peripheral neuropathy is helpful for the diagnostic procedure and
      contributes to the functional prognosis of the disease. Thus,
      electroneuromyography is essential in the algorithm for the diagnosis of
      inherited cerebellar ataxias, as well as brain MRI (looking especially for
      cerebellar atrophy) and the assessment of several biomarkers (alpha-foetoprotein,
      vitamin E, albumin, LDL cholesterol, lactic acid, phytanic acid).

PMID- 21195441
TI  - [Petrous plasmacytoma revealed by a painful peripheral facial palsy].
AB  - INTRODUCTION: The classical hypothesis of Bell's palsy, tempting in cases of
      peripheral facial palsy of rapid onset, must nevertheless be evoked with caution
      particularly if an intense pain is present, which should lead to search for a
      tumor of the skull base, especially the petrous bone. CASE REPORT: A 43-year-old
      man presented a peripheral facial palsy of rapidly progressive onset. A petrous
      bone tumor was diagnosed on the CT scan, which revealed an aspect of a glomic
      tumor or a metastatic lesion. The final histological diagnosis was plasmacytoma.
      DISCUSSION: This type of tumor has been rarely reported in this location. The
      radiological features are not specific at all, underlying the importance of
      searching for some associated signs such as a monoclonal protein and performing a
      histological examination when the firm diagnosis of a systemic disease like
      multiple myeloma has not been possible.

PMID- 21195442
TI  - [Building and validation of a test evaluating verbal recognition memory: The
      Forty test (f40)].
AB  - INTRODUCTION: Neuropsychologic evaluation is a primordial diagnostic tool.
      Numerous tests explore episodic memory but few tests exist to assess incidental
      verbal episodic memory or verbal recognition memory. This memory is however
      impaired early in certain neurodegenerative diseases such as Alzheimer's disease.
      Our objective was to create a test sensitive and specific to this cognitive
      dysfunction. METHOD: Our test was performed by 33 healthy volunteers and 51
      patients (19 with idiopathic Parkinson's disease, 16 with Alzheimer's disease at
      the prodromal stage and 16 with Alzheimer's disease). RESULTS AND DISCUSSION:
      Independently of age, education level and global cognitive impairment, the young
      and old healthy volunteers and the patients with idiopathic Parkinson's disease
      displayed results significantly better than the group of Alzheimer's disease at
      the prodromal stage and Alzheimer's disease patients. Our test appears to be
      sensitive to dysfunction of verbal recognition memory. A score of 30/40 or less
      on the Forty test discriminates 91% of subjects with a cortical pattern of
      memory. This test could be recommended for clinical neuropsychological practice.

PMID- 21195443
TI  - Characterisation of a non-pathogenic and non-protective infectious rabbit
      lagovirus related to RHDV.
AB  - The existence of non-pathogenic RHDV strains was established when a non-lethal
      virus named rabbit calicivirus (RCV) was characterised in 1996 in Italy. Since
      then, different RNA sequences related to RHDV have been detected in apparently
      healthy domestic and wild rabbits, and recently a new lagovirus was identified in
      Australia. We have characterised from seropositive healthy domestic rabbits a non
      lethal lagovirus that differs from RHDV in terms of pathogenicity, tissue tropism
      and capsid protein sequence. Phylogenetic analyses have revealed that it is close
      to the Ashington strain and to the RCV, but distinct. We proved experimentally
      that it is infectious but non-pathogenic and demonstrated that, contrary to the
      other described non-pathogenic lagoviruses, it induces antibodies that do not
      protect against RHDV. Our results indicate the existence of a gradient of cross
      protection between circulating strains, from non-protective, partially protective
      to protective strains, and highlight the extent of diversity within the genus
      Lagovirus.

PMID- 21195444
TI  - Glycosylation of minor envelope glycoproteins of porcine reproductive and
      respiratory syndrome virus in infectious virus recovery, receptor interaction,
      and immune response.
AB  - The role of N-glycosylation of the three minor envelope glycoproteins (GP2, GP3,
      and GP4) of porcine reproductive and respiratory syndrome virus (PRRSV) on
      infectious virus production, interactions with the receptor CD163, and
      neutralizing antibody production in infected pigs was examined. By mutation of
      the glycosylation sites in these proteins, the studies show that glycan addition
      at N184 of GP2, N42, N50 and N131 of GP3 is necessary for infectious virus
      production. Although single-site mutants of GP4 led to infectious virus
      production, mutation of any two sites in GP4 was lethal. Furthermore, the
      glycosylation of GP2 and GP4 was important for efficient interaction with CD163.
      Unlike PRRSVs encoding hypoglycosylated form of GP5 that induced significantly
      higher levels of neutralizing antibodies in infected piglets, PRRSVs encoding
      hypoglycosylated forms of GP2, GP3 or GP4 did not. These studies reveal the
      importance of glycosylation of these minor GPs in the biology of PRRSV.

PMID- 21195445
TI  - Evolutionary dynamics of rabies viruses highlights the importance of China rabies
      transmission in Asia.
AB  - Rabies in Asia is emerging as a serious public health issue. To explore the
      possible origin, phylogenetic relationships, and evolutionary dynamics of Asian
      Rabies viruses (RABV), we examined 200 complete nucleoprotein (N) gene sequences
      from RABV isolates in the region. Phylogeny supported the classification of Asian
      RABVs into five distinct clusters in lyssavirus genotype 1. Our geospatial and
      temporal analyses demonstrated that China appears to be the prime source of Asian
      RABVs. Understanding of rabies transmission and associated human activities, such
      as dog translocation, can help rabies control and elimination in Asia through
      collaborative efforts or programs.

PMID- 21195446
TI  - Performance and biofilm activity of nitrifying biofilters removing
      trihalomethanes.
AB  - Nitrifying biofilters seeded with three different mixed-culture sources removed
      trichloromethane (TCM) and dibromochloromethane (DBCM) with removals reaching 18%
      for TCM and 75% for DBCM. In addition, resuspended biofilm removed TCM,
      bromodichloromethane (BDCM), DBCM, and tribromomethane (TBM) in backwash batch
      kinetic tests, demonstrating that the biofilters contained organisms capable of
      biotransforming the four regulated trihalomethanes (THMs) commonly found in
      treated drinking water. Upon the initial and subsequent increased TCM addition,
      total ammonia nitrogen (TOTNH(3)) removal decreased and then reestablished,
      indicating an adjustment by the biofilm bacteria. In addition, changes in DBCM
      removal indicated a change in activity related to DBCM. The backwash batch
      kinetic tests provided a useful tool to evaluate the biofilm's bacteria. Based on
      these experiments, the biofilters contained bacteria with similar THM removal
      kinetics to those seen in previous batch kinetic experiments. Overall,
      performance or selection does not seem based specifically on nutrients, source
      water, or source cultures and most likely results from THM product toxicity, and
      the use of GAC media appeared to offer benefits over anthracite for biofilter
      stability and long-term performance, although the reasons for this advantage are
      not apparent based on research to date.

PMID- 21195447
TI  - Efficacy of monitoring and empirical predictive modeling at improving public
      health protection at Chicago beaches.
AB  - Efforts to improve public health protection in recreational swimming waters have
      focused on obtaining real-time estimates of water quality. Current monitoring
      techniques rely on the time-intensive culturing of fecal indicator bacteria (FIB)
      from water samples, but rapidly changing FIB concentrations result in management
      errors that lead to the public being exposed to high FIB concentrations (type II
      error) or beaches being closed despite acceptable water quality (type I error).
      Empirical predictive models may provide a rapid solution, but their effectiveness
      at improving health protection has not been adequately assessed. We sought to
      determine if emerging monitoring approaches could effectively reduce risk of
      illness exposure by minimizing management errors. We examined four monitoring
      approaches (inactive, current protocol, a single predictive model for all
      beaches, and individual models for each beach) with increasing refinement at 14
      Chicago beaches using historical monitoring and hydrometeorological data and
      compared management outcomes using different standards for decision-making.
      Predictability (R(2)) of FIB concentration improved with model refinement at all
      beaches but one. Predictive models did not always reduce the number of management
      errors and therefore the overall illness burden. Use of a Chicago-specific single
      sample standard-rather than the default 235 E. coli CFU/100 ml widely used
      together with predictive modeling resulted in the greatest number of open beach
      days without any increase in public health risk. These results emphasize that
      emerging monitoring approaches such as empirical models are not equally
      applicable at all beaches, and combining monitoring approaches may expand beach
      access.

PMID- 21195448
TI  - Transcriptional responses in juvenile Atlantic cod (Gadus morhua) after exposure
      to mercury-contaminated sediments obtained near the wreck of the German WW2
      submarine U-864, and from Bergen Harbor, Western Norway.
AB  - The main aim of the present work was to investigate the effects of mercury (Hg)
      enriched sediments on fish. Sediments near the sunken German WW2 submarine U-864,
      which according to historical documents included 67 tons of metallic Hg in its
      cargo, are enriched of Hg leaking from the wreckage. Juvenile Atlantic cod (Gadus
      morhua) were exposed to two field-collected polluted sediments (U-864: inorganic
      Hg and Bergen Harbor (Vagen): inorganic Hg, PCB and PAH) or two comparable
      reference sediments for 5 weeks in the laboratory, and transcriptional responses
      evaluated in gills and liver. Gills of fish exposed to the Hg-enriched sunken WW2
      submarine U-864 sediment contained four fold higher Hg levels compared to the
      control fish. An increase in Hg content in liver in the U-864 fish was also
      observed. The transcriptional results showed that calreticulin, HSP70 and heme
      oxygenase mRNA were significantly up-regulated in gills in fish exposed to the Hg
      enriched sediments, whereas calreticulin, heme oxygenase, transferrin and WAP65
      were significantly up-regulated and glutathione peroxidase 4B and zona pellucida
      3 were significantly down-regulated in liver tissue. In gills and liver of cod
      exposed to the mixed-contaminated Vagen sediment, CYP1A showed the highest
      induction. In conclusion, the experiment shows that sediment-bound Hg is
      available to the fish and affects the transcription of oxidative stress
      responsive enzymes, suggesting that the Hg-enriched sediments may negatively
      affect the local wildlife. Furthermore, the mixed contaminated sediments of Vagen
      affected similar responses in addition to Ah-receptor mediated responses
      reflecting exposure to PAHs and PCBs.

PMID- 21195449
TI  - Biodegradability of organic nanoparticles in the aqueous environment.
AB  - Synthetic nanoparticles have already been detected in the aquatic environment.
      Therefore, knowledge on their biodegradability is of utmost importance for risk
      assessment but such information is currently not available. Therefore, the
      biodegradability of fullerenes, single, double, multi-walled as well as COOH
      functionalized carbon nanotubes and cellulose and starch nanocrystals in aqueous
      environment has been investigated according to OECD standards. The
      biodegradability of starch and cellulose nanoparticles was also compared with the
      biodegradability of their macroscopic counterparts. Fullerenes and all carbon
      nanotubes did not biodegrade at all, while starch and cellulose nanoparticles
      biodegrade to similar levels as their macroscopic counterparts. However, neither
      comfortably met the criterion for ready biodegradability (60% after 28 days). The
      cellulose and starch nanoparticles were also found to degrade faster than their
      macroscopic counterparts due to their higher surface area. These findings are the
      first report of biodegradability of organic nanoparticles in the aquatic
      environment, an important accumulation environment for manmade compounds.

PMID- 21195450
TI  - Splenocyte apoptotic pathway in mice following oral exposure to cerium
      trichloride.
AB  - With their widespread application in agriculture, industry, culture, medicine,
      and daily life, lanthanide compounds are being brought into the ecological
      environment and human body through food chains. It is important to know the acute
      and chronic effects of lanthanides on the environment, nature balance, and the
      human body after their entry into bodies and the environment. Lanthanides have
      been demonstrated to cause spleen apoptosis and decreased immunity of mice, but
      very little is known about the molecular aspects of these mechanism. In order to
      understand the spleen apoptotic mechanism induced by intragastric administration
      of 2, 10 and 20 mg kg(-1) body weight CeCl(3) for consecutive 60 d, we
      investigated the cerium accumulation, apoptosis, the expression levels of the
      apoptosis-related cytokines into apoptosis-related genes and proteins. The
      results demonstrated that cerium had obvious accumulation in the mouse spleen,
      leading to the significant increase of the spleen indices and splenocyte
      apoptosis. Furthermore, CeCl(3) could effectively activate caspase-3 and -9,
      decrease the Bcl-2 the levels of gene and protein, and increase the levels of
      Bax, and cytochrome c genes and their protein expressions, and promote reactive
      oxygen species production. It implied CeCl(3)-induced apoptosis in the mouse
      spleen via intrinsic pathway. Our findings suggest the need for great caution to
      handle the lanthanides for workers and consumers.

PMID- 21195451
TI  - Myxomatous fibroadenoma of the breast: correlation with clinicopathologic and
      radiologic features.
AB  - Fibroadenoma is a frequently encountered benign tumor that must be differentiated
      from carcinoma. Fibroadenomas often exhibit myxedematous changes (myxomatous
      fibroadenoma). We focused on myxomatous fibroadenomas and evaluated their
      diagnostic imaging and clinicopathologic findings. We examined the (1)
      clinicopathologic findings of myxomatous fibroadenomas out of 113 fibroadenomas
      among 592 needle biopsy cases and (2) clinical findings of 27 patients with
      fibroadenoma who underwent surgical resection. One hundred thirteen (19%) of 592
      cases were fibroadenoma, of which 45 cases (40%) were myxomatous fibroadenoma.
      Based on ultrasonography findings, the depth to width ratio was significantly
      higher in the myxomatous fibroadenoma group (0.79 +/- 0.26) compared with the non
      myxomatous fibroadenoma group (0.64 +/- 0.26) (P < .01). Forty-two patients were
      subjected to needle biopsy to differentiate fibroadenoma from carcinomas based on
      ultrasonography and clinical findings, of which 13 cases (31%) were myxomatous
      fibroadenoma. These lesions showed a relatively round shape and increased
      posterior echo enhancement with internal hyperechogenicity on ultrasonography.
      Among 17 resected cases suspected of malignancy that showed rapid growth and/or
      size greater than 3 cm, 16 cases were myxomatous fibroadenoma. Tumors showing
      rapid growth and a relatively large size, a high depth to width ratio, a
      relatively round shape, and posterior echo enhancement with internal
      hyperechogenicity on ultrasonography require differentiation from (mucinous)
      carcinoma but are histologically more likely to be myxomatous fibroadenoma.
      Understanding the histologic features and combining the ultrasonography findings
      of myxomatous fibroadenomas may permit reduction in the number of unnecessary
      needle biopsies for tumor-forming lesions.

PMID- 21195452
TI  - Ovarian ependymomas of extra-axial type or central immunophenotypes.
AB  - We report the differential clinicopathologic and immunophenotypical features of 2
      pure ovarian ependymomas of extra-axial type with a predominant microcystic,
      anaplastic pattern occurring in patients aged 22 and 32 years and a unique
      myxopapillary pigmented ependymoma that originated within an ovarian mature
      cystic teratoma in a 35-year-old woman. The latter had a central nervous system
      phenotype different from that previously reported in ovarian ependymomas of extra
      axial types, being negative for estrogen and progesterone receptors, epithelial
      membrane antigen and cytokeratin 34betaE12, cell adhesion molecule 5.2, and
      cytokeratin 7. Furthermore, its benign behavior contrasted with the aggressive
      course of the other 2 ependymomas of extra-axial types, in which peritoneal
      invasion was present at the time of diagnosis. These findings illustrate that
      both central and extra-axial types of ependymoma show phenotypic variations that
      may point to either a derivation from different precursors or differentiation
      along diverse pathways. Thus, whereas ependymomas of extra-axial types would
      represent neometaplastic phenomena, those originated from the nervous tissue of
      teratomas resemble central nervous system ependymomas. Moreover, the
      dissimilarities between central and peripheral types of ependymoma would parallel
      the phenotypic differences present in primitive neural tumors of the female
      genital tract.

PMID- 21195453
TI  - Analysis of high level ozone concentrations using nonparametric methods.
AB  - Controlling emissions of air pollutants and establishing air quality objectives
      to improve and protect ambient air quality are very important tasks of
      Governments. Ozone (O(3)), one of those pollutants of concern, is not emitted
      directly into the atmosphere, but is a secondary pollutant produced by reaction
      between nitrogen dioxide (NO(2)), hydrocarbons and sunlight. High levels of ozone
      can produce harmful effects on human health and the environment in general.
      Therefore, the study of extreme values of ozone represents an important topic of
      research in environmental problems. Classical extreme value theory has been
      usually used in air-pollution studies. It consists of fitting a parametric
      generalized extreme value (GEV) distribution to a data set of extreme values and
      using the estimated distribution to compute quantities like the probability of
      exceedance, the quantiles, the return levels or the mean return periods. In this
      paper, we propose nonparametric methods to estimate those quantities.
      Additionally, nonparametric estimators of the trends of very high values of ozone
      are proposed. The nonparametric estimators are applied to real samples of maximum
      ozone values obtained from several monitoring stations belonging to the Automatic
      Urban and Rural Network (AURN) from the UK. Results show that nonparametric
      estimators work satisfactorily, generally outperforming the behaviour of
      classical parametric estimators.

PMID- 21195454
TI  - Trace metal depositional patterns from an open pit mining activity as revealed by
      archived avian gizzard contents.
AB  - Archived samples of blue grouse (Dendragapus obscurus) gizzard contents,
      inclusive of grit, collected yearly between 1959 and 1970 were analyzed for
      cadmium, lead, zinc, and copper content. Approximately halfway through the 12
      year sampling period, an open-pit copper mine began activities, then ceased
      operations 2 years later. Thus the archived samples provided a unique opportunity
      to determine if avian gizzard contents, inclusive of grit, could reveal patterns
      in the anthropogenic deposition of trace metals associated with mining
      activities. Gizzard concentrations of cadmium and copper strongly coincided with
      the onset of opening and the closing of the pit mining activity. Gizzard zinc and
      lead demonstrated significant among year variation; however, maximum
      concentrations did not correlate to mining activity. The archived gizzard
      contents did provide a useful tool for documenting trends in metal depositional
      patterns related to an anthropogenic activity. Further, blue grouse ingesting
      grit particles during the time of active mining activity would have been exposed
      to toxicologically significant levels of cadmium. Gizzard lead concentrations
      were also of toxicological significance but not related to mining activity. This
      type of "pulse" toxic metal exposure as a consequence of open-pit mining activity
      would not necessarily have been revealed through a "snap-shot" of soil, plant or
      avian tissue trace metal analysis post-mining activity.

PMID- 21195455
TI  - Possible association between nickel and chromium and oral cancer: a case-control
      study in central Taiwan.
AB  - Oral cancer is one of the most common cancers in Taiwan. Changhua County, in
      central Taiwan, has an extremely high prevalence of oral cancer, along with a
      high concentration of metal-related industries and soil metal contamination. The
      aim of this study was to clarify the possible association between metals and oral
      cancer within this specific area. This study recruited 101 oral cancer patients
      and 104 controls from the Changhua Christian Hospital. All subjects completed a
      questionnaire that asked about demographic information; cigarette, alcohol, and
      betel quid use; and environmental and occupational exposure history. Blood
      samples were collected and tested for metal concentrations with inductively
      coupled plasma mass spectrometry. A multiple logistic regression model
      illustrated that oral cancer was significantly associated with the blood levels
      of nickel and chromium (both with P<0.0001) after controlling for potential
      confounders. This study suggested a potential role of these two metals in the
      mechanism of oral cancer development.

PMID- 21195456
TI  - Improved tolerance of maize (Zea mays L.) to heavy metals by colonization of a
      dark septate endophyte (DSE) Exophiala pisciphila.
AB  - Dark septate endophytes (DSE) are ubiquitous and abundant in stressful
      environments including heavy metal (HM) stress. However, our knowledge about the
      roles of DSE in improving HM tolerance of their host plants is poor. In this
      study, maize (Zea mays L.) was inoculated with a HM tolerant DSE strain Exophiala
      pisciphila H93 in lead (Pb), zinc (Zn), and cadmium (Cd) contaminated soils. E.
      pisciphila H93 successfully colonized and formed typical DSE structures in the
      inoculated maize roots. Colonization of E. pisciphila H93 alleviated the
      deleterious effects of excessive HM supplements and promoted the growth of maize
      (roots and shoots) under HM stress conditions, though it significantly decreased
      the biomass of inoculated maize under no HM stress. Further analysis showed that
      the colonization of E. pisciphila H93 improved the tolerance of maize to HM by
      restricting the translocation of HM ions from roots to shoots. This study
      demonstrated that under higher HM stress, such a mutual symbiosis between E.
      pisciphila and its host (maize) may be an efficient strategy to survive in the
      stressful environments.

PMID- 21195457
TI  - Impact of calcium and TOC on biological acidification assessment in Norwegian
      rivers.
AB  - Acidification continues to be a major impact in freshwaters of northern Europe,
      and the biotic response to chemical recovery from acidification is often not a
      straightforward process. The focus on biological recovery is relevant within the
      context of the EU Water Framework Directive, where a biological monitoring system
      is needed that detects differences in fauna and flora compared to undisturbed
      reference conditions. In order to verify true reference sites for biological
      analyses, expected river pH is modeled based on Ca and TOC, and 94% of
      variability in pH at reference sites is explained by Ca alone, while 98% is
      explained by a combination of Ca and TOC. Based on 59 samples from 28 reference
      sites, compared to 547 samples from 285 non-reference sites, the impact of
      calcium and total organic carbon (TOC) on benthic algae species composition,
      expressed as acidification index periphyton (AIP), is analyzed. Rivers with a
      high Ca concentration have a naturally higher AIP, and TOC affects reference AIP
      only at low Ca concentrations. Four biological river types are needed for
      assessment of river acidification in Norway based on benthic algae: very calcium
      poor, humic rivers (Ca<1 mg/l and TOC>2 mg/l); very calcium-poor, clear rivers
      (Ca<1 mg/l and TOC<2 mg/l); calcium-poor rivers (Ca between 1 and 4 mg/l);
      moderately calcium rich rivers (Ca>4 mg/l). A biological assessment system for
      river acidification in Norway based on benthic algae is presented, following the
      demands of the Water Framework Directive.

PMID- 21195458
TI  - Application of nonparametric regression methods to study the relationship between
      NO2 concentrations and local wind direction and speed at background sites.
AB  - Background concentrations of nitrogen dioxide (NO(2)) are not constant but vary
      temporally and spatially. The current paper presents a powerful tool for the
      quantification of the effects of wind direction and wind speed on background
      NO(2) concentrations, particularly in cases where monitoring data are limited. In
      contrast to previous studies which applied similar methods to sites directly
      affected by local pollution sources, the current study focuses on background
      sites with the aim of improving methods for predicting background concentrations
      adopted in air quality modelling studies. The relationship between measured NO(2)
      concentration in air at three such sites in Ireland and locally measured wind
      direction has been quantified using nonparametric regression methods. The major
      aim was to analyse a method for quantifying the effects of local wind direction
      on background levels of NO(2) in Ireland. The method was expanded to include wind
      speed as an added predictor variable. A Gaussian kernel function is used in the
      analysis and circular statistics employed for the wind direction variable. Wind
      direction and wind speed were both found to have a statistically significant
      effect on background levels of NO(2) at all three sites. Frequently environmental
      impact assessments are based on short term baseline monitoring producing a
      limited dataset. The presented non-parametric regression methods, in contrast to
      the frequently used methods such as binning of the data, allow concentrations for
      missing data pairs to be estimated and distinction between spurious and true
      peaks in concentrations to be made. The methods were found to provide a realistic
      estimation of long term concentration variation with wind direction and speed,
      even for cases where the data set is limited. Accurate identification of the
      actual variation at each location and causative factors could be made, thus
      supporting the improved definition of background concentrations for use in air
      quality modelling studies.

PMID- 21195459
TI  - High thrombin activatable fibrinolysis inhibitor levels are associated with an
      increased risk of premature peripheral arterial disease.
AB  - BACKGROUND: Previous studies suggested that hypofibrinolysis is associated with
      increased risk of peripheral arterial disease. Thrombin activatable fibrinolysis
      inhibitor (TAFI) has been identified as an important inhibitor of fibrinolysis.
      The aim of our study was to assess the role of TAFI in young patients with
      peripheral arterial disease. METHODS: In a single-center case-control study we
      measured plasma TAFI antigen levels and functional TAFI in consecutive young
      patients (men 18-45 years and women 18-55 years) with a first manifestation of
      peripheral arterial disease and compared these with a population-based control
      group. RESULTS: A total of 47 peripheral arterial disease patients and 141
      controls (mean age 43) were included. Intact TAFI antigen levels were
      significantly higher in patients with peripheral arterial disease (112.4+/-21.1%)
      than in controls (104.9+/-19.9%, p=0.03). The risk of peripheral arterial disease
      increased with 18% (OR 1.18; CI 1.01-1.34) per 10% increase of TAFI antigen.
      Functional TAFI levels were slightly higher in patients compared to controls,
      however this difference was not significant. For individuals with the highest
      functional TAFI levels, above the 90th percentile, the increased risk for
      peripheral arterial disease was most pronounced (OR 3.1; CI 1.02-9.41).
      CONCLUSION: High TAFI levels are associated with increased risk of premature
      peripheral arterial disease.

PMID- 21195460
TI  - Influence of GGCX genotype on warfarin dose requirements in Chinese patients.
AB  - INTRODUCTION: It has been widely accepted that genetic factors were the major
      sources of the variation in warfarin dose. This study is intended to investigate
      whether the 3261G>A variation in GGCX gene influences stable warfarin dose in
      Chinese patient population. MATERIALS AND METHODS: A total of 217 patients with
      stable warfarin dose were enrolled. Genomic DNA was extracted from each subject
      and the genotype of GGCX 3261G>A was determined by using of denaturing high
      performance liquid chromatography (DHPLC). Least significant difference tests
      (LSDs) were used to compare dose with genotypes. Analysis of variance (ANVOA) was
      used to calculate the proportion of warfarin dose that could be explained by
      variation in genotype. RESULTS: In the total of 217 subjects, 84 patients (38.7%)
      were GG homozygote, whereas 117 (53.9%) were GA heterozygote and 16 (7.4%) were
      AA homozygote. Patients with the GGCX 3261AA genotype had a significantly higher
      average daily maintenance dose (3.39 +/- 1.40 mg) than those with the GG genotype
      (2.69 +/- 1.07 mg; P=0.027), and GGCX 3261G>A explains 2.3% of the univariate
      warfarin dose variance. CONCLUSION: GGCX 3261G>A may affect warfarin dose
      requirements, and showed a small but significant effect on warfarin dose in a
      Chinese patient population.

PMID- 21195461
TI  - Evaluating surface bound rTFPI through an in vitro model of vessel wall injury.
AB  - INTRODUCTION: Injury to the surrounding vessel wall is one of the major reasons
      for failure of implantable medical devices. The surgical procedure itself or the
      altered flow conditions after implantation can cause damage to the vessel wall.
      This damage exposes tissue factor (TF), the initiator of the extrinsic pathway of
      coagulation. One approach to combat thrombosis is to use an anticoagulant on the
      surface of the device. The primary aim of this study is to develop a simplified
      physiologically relevant in vitro model of vessel wall injury to study the
      mechanisms by which immobilized recombinant tissue factor pathway inhibitor
      (rTFPI) effectively inhibits TF initiated thrombosis. MATERIALS AND METHODS: A
      two well chamber slide was used for the study. Fibroblasts were cultured on the
      upstream portion of the slide. Fibroblast cells stimulated with TNF-alpha acted
      as a source of surface TF. The downstream portion of the slide was coated with
      rTFPI. A mixture of FX, FVIIa and calcium was perfused over the slides to
      generate FXa. Effluent collected at the outlet was used to analyze the inhibition
      of this surface generated FXa by the rTFPI present downstream. RESULTS AND
      CONCLUSIONS: Different shear rates and rTFPI densities were used to study this
      effect. In most cases rTFPI inhibited FXa generated upstream as a function of the
      wall shear rate and rTFPI dosage (surface density). This study shows the
      effectiveness of the surface bound inhibitor when FXa is generated from an
      upstream injury site and the bulk of FXa is near the wall.

PMID- 21195462
TI  - Involvement of cathepsin D during tail regression in tadpoles of the common
      Indian tree frog, Polypedates maculatus (Anura: Rhacophoridae).
AB  - Cathepsin D, an aspartyl protease, plays a key role in the metabolic degradation
      of intracellular proteins in an acidic milieu of lysosomes. Proteolysis plays an
      essential role in anuran tail regression and a wide variety of thyroid hormone
      induced proteolytic enzymes have been reported to be involved in the regressing
      tail. The present study describes the trend of specific activity of cathepsin D
      in the tail of different developmental stages and immunohistochemical
      localization of cathepsin D during degradation of various tail tissues in the
      tadpoles of Polypedates maculatus. Cathepsin D has been found to be involved in
      the degradation of major tail tissues such as epidermis, muscle, spinal cord,
      notochord cells and blood cells in the regressing tail. Interestingly, it has
      also been found to be involved in the pre-regressing tail prior to visible tail
      regression. In addition, melanocytes have been described to be associated with
      degradation of different tail tissues.

PMID- 21195463
TI  - Urodynamic profile of diabetic patients with lower urinary tract symptoms:
      association of diabetic cystopathy with autonomic and peripheral neuropathy.
AB  - OBJECTIVES: To evaluate the association between diabetic cystopathy (DC) and
      neuropathy (autonomic and peripheral) in patients with diabetes mellitus (DM)
      presenting with lower urinary tract symptoms (LUTS). METHODS: Men with DM who
      presented with bothersome LUTS were enrolled from January 2008 to June 2009.
      Their demographic and clinical profiles were noted. Multichannel urodynamic
      studies were performed using the Solar Silver digital urodynamic apparatus. Hand
      and foot sympathetic skin responses, and motor and sensory nerve-conduction
      velocity studies were performed using the Meditronic electromyographic/evoked
      potentials system. RESULTS: A total of 52 men (mean age 61.3 +/- 12.1 years, DM
      duration 11.0 +/- 7.5 years) completed the study protocol. Of these 52 men,
      abnormal sympathetic skin responses, motor and sensory nerve-conduction velocity
      studies, and combined neuropathy (all 3 tests abnormal) were noted in 80.7%
      57.7%, 57.7%, and 51.9%, respectively. Urodynamic studies showed impaired first
      sensation (>250 mL), increased capacity (>600 mL), detrusor underactivity,
      detrusor overactivity, high postvoid residual urine volume (more than one third
      of capacity), and bladder outlet obstruction (Abrams-Griffiths number >40) in
      23.1%, 25.0%, 78.8%, 38.5%, 65.4%, and 28.8% of the men, respectively. Both
      sensory and motor DC correlated with abnormal motor and sensory nerve-conduction
      velocity studies (P = .015 and P = .005, respectively). Only motor DC correlated
      with abnormal sympathetic skin responses (P = .015). The correlations were
      stronger in the presence of combined neuropathy (sensory DC, P = .005; motor DC,
      P = .0001). CONCLUSIONS: Men with DM and LUTS can present with varied urodynamic
      findings, apart from the classic sensory or motor cystopathy. A large proportion
      of these patients will have electrophysiologic evidence of neuropathy, and
      electrophysiologic evidence of neuropathy can moderately predict the presence of
      cystopathy.

PMID- 21195464
TI  - Subclinical varicocele and sports: a longitudinal study.
AB  - OBJECTIVES: To evaluate the influence of physical activity on the evolution of
      subclinical varicocele because subclinical and clinical varicoceles are common in
      adolescents. METHODS: The study enrolled healthy male volunteers (athletes and
      nonathletes) and athletes with subclinical varicocele from October 2006 to March
      2007. A fourth group of nonathletes with subclinical varicocele was created.
      Subclinical varicocele was defined as spermatic vein reflux detected with Doppler
      velocimetry only with the Valsalva maneuver. All patients were pubertal boys of
      14-16 years old. Those practicing sports on a regular basis >=3 times weekly for
      >=2 consecutive hours were considered athletes. The boys were examined every year
      for 3 years from October 2006 to March 2010. At each examination, each patient
      underwent Doppler velocimetry and testicular volume measurements with a standard
      orchidometer. The rate of progression to a clinically palpable varicocele and its
      relationship to sport practice was also assessed. RESULTS: The follow-up
      compliance rate was 80%. The rate of progression to a clinically palpable
      varicocele was significantly greater in the athletes with a subclinical
      varicocele than in the healthy group (athletes and nonathletes) without a
      subclinical varicocele (36% vs 5%, respectively; P < .05). The probability of
      developing a subclinical varicocele for healthy athletes and healthy nonathletes
      was similar (23% vs 20%, respectively). CONCLUSIONS: Subclinical varicocele
      should be considered as the first stage of varicocele development. Although
      sports practice seemed to cause progression to a clinical varicocele, this
      finding was confirmed only in patients already affected by spermatic vein reflux
      (subclinical varicocele).

PMID- 21195465
TI  - Comparison of tumor control and toxicity outcomes of high-dose intensity
      modulated radiotherapy and brachytherapy for patients with favorable risk
      prostate cancer.
AB  - OBJECTIVES: To compare the long-term, prostate-specific antigen relapse-free
      survival outcome and incidence of toxicity for patients with low-risk prostate
      cancer who underwent brachytherapy or intensity-modulated radiotherapy (RT).
      METHODS: A total of 729 consecutive patients underwent brachytherapy (n = 448;
      prescription dose 144 Gy) or intensity-modulated RT alone (n = 281; prescription
      dose 81 Gy). The prostate-specific antigen relapse-free survival using the nadir
      plus 2 ng/mL definition and late toxicity using the National Cancer Institute's
      Common Terminology Criteria for Adverse Events were determined. RESULTS: The 7
      year prostate-specific antigen relapse-free survival rate for the brachytherapy
      and intensity-modulated RT groups was 95% and 89% for low-risk patients,
      respectively (P = .004). Cox regression analysis demonstrated that brachytherapy
      was associated with improved prostate-specific antigen relapse-free survival,
      even after adjustment for other variables. The incidence of metastatic disease
      between treatment sessions was low for both treatment groups. Late grade 2
      gastrointestinal toxicity was observed in 5.1% and 1.4% of the brachytherapy and
      intensity-modulated RT groups, respectively (P = .02). No significant differences
      were seen between treatment groups for late grade 3 or greater rectal
      complications (brachytherapy 1.1% and intensity-modulated RT 0%; P = .19). Late
      grade 2 urinary toxicity occurred more often in the brachytherapy group than in
      the intensity-modulated RT group (15.6% and 4.3%, respectively; P < .0001). No
      significant differences were seen between the 2 treatment groups for late grade 3
      urinary toxicity (brachytherapy 2.2% and intensity-modulated RT 1.4%; P = .62).
      CONCLUSIONS: Among low-risk prostate cancer patients, the 7-year biochemical
      tumor control was superior for intraoperatively planned brachytherapy compared
      with high-dose intensity-modulated RT. Although significant toxicities were
      minimal for both groups, modest, but significant, increases in grade 2 urinary
      and rectal symptoms were noted for brachytherapy compared with intensity
      modulated RT.

PMID- 21195466
TI  - Prostate size is not associated with recovery of sexual function after minimally
      invasive radical prostatectomy.
AB  - OBJECTIVES: To investigate the association of prostate weight with recovery of
      sexual function after minimally invasive radical prostatectomy. METHODS: Between
      April 2001 and September 2007, two surgeons performed 856 consecutive
      laparoscopic radical prostatectomies for clinically localized prostate cancer.
      Patients were stratified into three groups by prostate weight: <35 g, 35-70 g,
      and >70 g. Sexual and urinary outcomes were assessed prospectively using the
      Expanded Prostate Cancer Index Composite (EPIC) questionnaire. Patients who
      underwent nerve sparing (unilateral or bilateral) with complete preoperative EPIC
      data, a minimum preoperative Sexual Health Inventory for Men score >=21, and a
      minimum of 3 months of complete postoperative EPIC data were included in the
      analysis. RESULTS: Of the cohort of 856 men, 324 (38%) had complete, evaluable
      data and met the inclusion criteria for this study. Preoperatively, there were no
      significant differences by prostate weight in the EPIC sexual function or bother
      subscale scores or the proportion of patients participating in sexual
      intercourse. Postoperatively, we observed statistically similar returns to
      baseline EPIC sexual function and bother subscale scores and participation in
      sexual intercourse across all gland weight groups at all time points. EPIC sexual
      domain scores and the proportions of patients participating in sexual intercourse
      continued to increase up to 24 months postoperatively, but no group returned to
      preoperative function at any sampling point. CONCLUSIONS: Prostate size is not
      associated with postoperative recovery of sexual function in men undergoing
      minimally invasive radical prostatectomy.

PMID- 21195467
TI  - Role of genetics in azoospermia.
AB  - OBJECTIVE: To review established genetic causes of azoospermia, the most severe
      form of male infertility, and help clinicians, scientists, and infertile couples
      considering assisted reproductive technologies (ART) to understand the complexity
      of the disorder and to maximize the chances of having a healthy infant through
      proper counseling and treatment. METHOD: An initial literature search was
      performed on PubMed using the key words "azoospermia" "oligospermia," and
      "genetics." The results were limited to the studies on humans and written in
      English, which were written within last 10 years. Although preliminary query
      results showed more than 900 articles, further queries using key words, such as
      "Y chromosome," "monogenics," "aneuploidy," "mitochondrial DNA," and
      "epigenetics," along with "azoospermia," narrowed the results to 30 papers, which
      were included in the present study. RESULTS: Genetic defects causing azoospermia
      were categorized into two large categories: chromosomal and nonchromosomal.
      Chromosomal defects were further categorized into (1) structural abnormalities,
      such as Y chromosome micro/macrodeletions, chromosomal inversions, and
      translocations; and (2) numerical abnormalities, also known as aneuploidy.
      Nonchromosomal defects included sperm mitochondrial genome defects and epigenetic
      alterations of genome. CONCLUSIONS: As a result of advancements in ART,
      understanding the potential implications of genetic disorders for infertile
      couples is critical. Analysis of a potential genetic role in azoospermia holds
      promise to expand our knowledge to evaluate male infertility and to guide
      treatments.

PMID- 21195468
TI  - Effects of silencing transforming growth factor-beta1 by RNA interference plasmid
      on rat renal allograft fibrosis using Smads pathway.
AB  - OBJECTIVES: To evaluate the effects of transforming growth factor (TGF)-beta1 RNA
      interference plasmid on rat renal allograft fibrosis and to explore its
      mechanisms. METHODS: A Sprague-Dawley to Wistar rat transplant kidney-sclerosis
      accelerated model was constructed and transfected with short hairpin RNA-TGF
      beta1 based on the hydromechanics. Kidney and blood samples were collected at the
      first, second, and third months after transplantation. Reverse transcriptase
      polymerase chain reaction and Western blotting were used to detect the expression
      of TGF-beta1, phosphorylated Smad3/7, E-cadherin, and type I collagen. The
      fibrosis extent was assessed using Masson staining. The immunohistochemical
      staining of E-cadherin and alpha-smooth muscle actin were used to label the
      tubular epithelial cells and fibroblast, respectively. RESULTS: The blood urea
      nitrogen and serum creatinine were lower in the plasmid group than in the control
      groups (P <.05 and P <.01, respectively). The expression of TGF-beta1 was
      significantly inhibited by the plasmid and its target gene type I collagen (P
      <.05 or P <.01), in which the signal proteins of phosphorylated Smad3 was
      downregulated and phosphorylated Smad7 was upregulated. Also, the fibrosis of the
      renal allograft was improved and milder fibrosis was present in the plasmid
      group. In addition, short hairpin RNA-TGF-beta1 plasmid maintained the expression
      of E-cadherin on tubular epithelial cells, resulting in inhibition of cell
      transdifferentiation from epithelial cells to fibroblast. CONCLUSIONS: Our
      results suggest that short hairpin RNA-TGF-beta1 plasmid could prevent the
      fibrosis of renal allografts. The mechanism might be associated with its effects
      of downregulating phosphorylated Smad3 and upregulating phosphorylated Smad7,
      leading to the suppression of epithelial-myofibroblast transdifferentiation and
      extracellular matrix synthesis.

PMID- 21195469
TI  - Characterization of alpha1-adrenoceptor subtypes mediating contraction in human
      isolated ureters.
AB  - OBJECTIVES: To characterize the contractile functions of the alpha(1)
      adrenoceptor (AR) subtypes present in the human ureter. METHODS: Specimens were
      taken from patients with renal cancer ("upper ureters;" n = 51) or bladder cancer
      ("lower ureters;" n = 23) who had not been treated by chemotherapy, radiation
      therapy, or immunotherapy before surgery. Patients systemically taking an
      alpha(1)-AR agonist or antagonist were excluded from this study. The effects of
      alpha(1)-AR antagonists against phenylephrine (alpha(1)-AR agonist)-induced
      contractions were evaluated in human isolated ureteral preparations. RESULTS:
      Pooled data from all ureters showed that phenylephrine (alpha(1)-AR agonist)
      induced a concentration-dependent tonic contraction (pD(2) value, 4.92 +/- 011).
      The phenylephrine-induced maximum contraction was significantly greater in lower
      ureters than in upper ones. Prazosin (nonselective alpha(1)-AR antagonist),
      silodosin (selective alpha(1A)-AR antagonist), and BMY-7378 (selective alpha(1D)
      AR antagonist) all shifted the concentration-contractile response curve for
      phenylephrine to the right, the rank order of potencies in all ureters (pK(B)
      values) being silodosin (9.72 +/- 0.14) > prazosin (8.64 +/- 0.08) > BMY-7378
      (7.04 +/- 0.14). The alpha(1A)-AR antagonist silodosin was thus much more potent
      than the other 2 antagonists. CONCLUSIONS: Our results suggest that among
      alpha(1)-ARs, the alpha(1A) subtype plays the major role in contraction in the
      human ureter.

PMID- 21195470
TI  - Personal sampling of small mold spores using slit cassettes.

PMID- 21195472
TI  - Wasp venom immunotherapy induces activation and homing of CD4(+)CD25(+) forkhead
      box protein 3-positive regulatory T cells controlling T(H)1 responses.
AB  - BACKGROUND: Despite a growing interest in CD4(+)CD25(+) forkhead box protein 3
      (Foxp3)-positive regulatory T (Treg) cells, the fundamental parameters of the
      activation and homing of these cells during wasp venom immunotherapy (VIT) are
      largely unknown. OBJECTIVE: We investigated longitudinally the phenotype and
      function of Treg cells in a well-characterized homogeneous group of patients with
      wasp venom allergy during VIT. METHODS: In 30 patients peripheral Treg cells were
      ex vivo monitored for their activation status and homing capacities by means of
      flow cytometric analysis before and after 1 and 6 months of VIT. In addition, the
      in vitro suppressive activity of Treg cells, as well as cytokine secretion, in
      response to wasp venom was analyzed. RESULTS: One month after initiating VIT, the
      proportion of both CD4(+)CD25(+)Foxp3(+) and CD4(+)Foxp3(+) Treg cells
      significantly decreased in peripheral blood. Coexpression of the lymph node
      homing receptors CCR7/CD62L were induced in CD4(+)Foxp3(+)CD45RO(+) Treg cells,
      indicating recirculation of VIT-activated Treg cells in secondary lymphoid
      organs. In vivo imaging by means of color duplex ultrasonography of the axillary
      draining lymph nodes demonstrated a VIT-induced 4-fold augmentation in afferent
      arterial blood flow. Furthermore, increased activation markers (CD45RO and HLA
      DR) of Treg cells correlated with effective in vitro suppression of wasp venom
      driven T-cell proliferation. After 1 month of VIT, Treg cell depletion in vitro
      greatly enhanced wasp venom-induced IFN-gamma secretion. CONCLUSIONS: Allergen
      exposure during VIT simultaneously induces the activation and selective homing of
      circulating Treg cells. Functionally, on the one hand, Treg cells balance the
      immune reaction toward tolerance, and on the other hand, they are involved in
      controlling overwhelming T(H)1 responses.

PMID- 21195471
TI  - Heterogeneity of severe asthma in childhood: confirmation by cluster analysis of
      children in the National Institutes of Health/National Heart, Lung, and Blood
      Institute Severe Asthma Research Program.
AB  - BACKGROUND: Asthma in children is a heterogeneous disorder with many phenotypes.
      Although unsupervised cluster analysis is a useful tool for identifying
      phenotypes, it has not been applied to school-age children with persistent asthma
      across a wide range of severities. OBJECTIVES: This study determined how children
      with severe asthma are distributed across a cluster analysis and how well these
      clusters conform to current definitions of asthma severity. METHODS: Cluster
      analysis was applied to 12 continuous and composite variables from 161 children
      at 5 centers enrolled in the Severe Asthma Research Program. RESULTS: Four
      clusters of asthma were identified. Children in cluster 1 (n = 48) had relatively
      normal lung function and less atopy. Children in cluster 2 (n = 52) had slightly
      lower lung function, more atopy, and increased symptoms and medication use.
      Cluster 3 (n = 32) had greater comorbidity, increased bronchial responsiveness,
      and lower lung function. Cluster 4 (n = 29) had the lowest lung function and the
      greatest symptoms and medication use. Predictors of cluster assignment were
      asthma duration, the number of asthma controller medications, and baseline lung
      function. Children with severe asthma were present in all clusters, and no
      cluster corresponded to definitions of asthma severity provided in asthma
      treatment guidelines. CONCLUSION: Severe asthma in children is highly
      heterogeneous. Unique phenotypic clusters previously identified in adults can
      also be identified in children, but with important differences. Larger validation
      and longitudinal studies are needed to determine the baseline and predictive
      validity of these phenotypic clusters in the larger clinical setting.

PMID- 21195473
TI  - Biomimetic dentin desensitizer based on nano-structured bioactive glass.
AB  - OBJECTIVES: This study evaluated the ability of a novel sol-gel bioactive glass,
      in conjunction with appropriate carrier vehicles, to reduce dentinal fluid flow,
      with an eye toward reducing dentinal hypersensitivity. METHODS: Experiments were
      conducted to measure the reduction in tubule fluid flow after treatment of cut
      tooth surfaces with sol-gel bioactive glass particles in several carrier
      vehicles. Surfaces were also examined after exposure to brushing and acidic
      solutions. A non-bioactive particulate glass was compared. RESULTS: Tubular
      occlusion produced by the bioactive glass was observed via SEM and a sustained
      reduction in hydrodynamic conductance was measured after exposure to various
      fluids and brushing. CONCLUSIONS: This new material may be used with the tested
      carriers to significantly and durably reduce tubule fluid flow, ultimately
      resulting in reduced dentinal hypersensitivity.

PMID- 21195474
TI  - Pre-osteoblast infiltration and differentiation in highly porous apatite-coated
      PLLA electrospun scaffolds.
AB  - Electrospun polymer/apatite composite scaffolds are promising candidates as
      functional bone substitutes because of their ability to allow pre-osteoblast
      attachment, proliferation, and differentiation. However these structures usually
      lack an adequate pore size to permit sufficient cell migration and colonization
      of the scaffold. To overcome this limitation, we developed an apatite-coated
      electrospun PLLA scaffold with varying pore size and porosity by utilizing a
      three-step water-soluble PEO fiber inclusion, dissolution, and mineralization
      process. The temporal and spatial dynamics of cell migration into the scaffolds
      were quantified to determine the effects of enhanced pore size and porosity on
      cell infiltration. MC3T3-E1 pre-osteoblast migration into the scaffolds was found
      to be a function of both initial PEO content and time. Scaffolds with greater
      initial PEO content (50% and 75% PEO) had drastically accelerated cell
      infiltration in addition to enhanced cell distribution throughout the scaffold
      when compared to scaffolds with lower PEO content (0% and 25% PEO). Furthermore,
      scaffolds with an apatite substrate significantly upregulated MC3T3-E1 alkaline
      phosphatase activity, osteocalcin content, and cell-mediated mineralization as
      compared to PLLA alone. These findings suggest that such a scaffold enhances pre
      osteoblast infiltration, colonization, and maturation in vitro and may lead to
      overall improved bone formation when implanted in vivo.

PMID- 21195475
TI  - Review: The effects of oxygen on normal and pre-eclamptic placental tissue-
      insights from metabolomics.
AB  - Placental dysfunction is central to many complications of human pregnancy
      including pre-eclampsia (PE), intra-uterine growth restriction (IUGR) and
      stillbirth. The precise molecular pathophysiology of placental dysfunction in
      these conditions is not known, although oxidative and nitrative stresses have
      been implicated. Metabolites are low molecular weight chemicals which play an
      important role in biological function, primarily through metabolism and
      regulation of biological processes. The holistic study of metabolites, defined as
      metabolomics or metabolic profiling, has the objective to detect and identify
      all, or a large complement of all metabolites. Metabolomics is applied to
      discover new knowledge regarding biological processes and systems. We
      hypothesised that a metabolomic strategy could (1) provide a reproducible
      technique to investigate the intracellular metabolism of placental tissue and
      also metabolites consumed from or secreted in to the extracellular 'metabolic
      footprint' of in vitro culture systems (2) identify metabolic related differences
      in placental tissue culture systems subjected to perturbations in oxygen tension
      and from pregnancies complicated by PE. We review our early studies which
      demonstrate that a reproducible experimental protocol is required, including the
      preparation of culture medium and the site of the placenta applied for sampling
      tissue. We have detected changes in the intracellular metabolome and metabolic
      footprint of placental tissue in response to altered oxygen tension and PE. We
      have demonstrated that placental tissue from uncomplicated pregnancies cultured
      in 1% oxygen (hypoxia) had metabolic similarities to explants from PE pregnancies
      cultured at 6% oxygen (normoxia). Metabolites requiring further study include
      lipids, glutamate and glutamine and metabolites related to tryptophan,
      leukotriene and prostaglandin metabolism. Metabolomics has the potential to
      identify changes in clinical conditions, such as PE, that are associated with
      placental molecular pathophysiology.

PMID- 21195476
TI  - Elsevier Trophoblast Research Award lecture: The multifaceted role of Nodal
      signaling during mammalian reproduction.
AB  - Nodal, a secreted signaling protein in the transforming growth factor-beta (TGF
      beta) superfamily, has established roles in vertebrate development. However,
      components of the Nodal signaling pathway are also expressed at the maternal
      fetal interface and have been implicated in many processes of mammalian
      reproduction. Emerging evidence indicates that Nodal and its extracellular
      inhibitor Lefty are expressed in the uterus and complex interactions between the
      two proteins mediate menstruation, decidualization and embryo implantation.
      Furthermore, several studies have shown that Nodal from both fetal and maternal
      sources may regulate trophoblast cell fate and facilitate placentation as both
      embryonic and uterine-specific Nodal knockout mouse strains exhibit disrupted
      placenta morphology. Here we review the established and prospective roles of
      Nodal signaling in facilitating successful pregnancy, including recent evidence
      supporting a potential link to parturition and preterm birth.

PMID- 21195477
TI  - Regulation of BCR signaling.
AB  - B cells and antibodies are important elements of acquired humoral immunity in the
      fight against various pathogens, and signals through the B cell receptor (BCR)
      are crucial for the development, activation and differentiation of B cells. Our
      laboratory has focused on understanding the molecular mechanisms of BCR-mediated
      signaling cascades that regulate these processes in B cells. In this review, I
      will briefly present our studies that have clarified the molecular components of
      signaling cascades, mainly focusing on data using DT40 B cells and their genetic
      variants.

PMID- 21195479
TI  - Attachment patterns and emotion regulation strategies in the second year.
AB  - With the aim of studying the relationship between methods of emotion regulation
      and quality of attachment we examined 39 infants with different patterns of
      attachment, of whom 20 were classified as secure (B), 12 as avoidant (A) and 7 as
      resistant (C), assessing the regulatory strategies adopted by them during the
      Strange Situation at 13 months. Secure infants used strategies of positive social
      engagement more than insecure avoidant infants, while resistant infants displayed
      greater negative social engagement and less object orientation than the other two
      groups. Avoidant infants adopted positive and negative hetero-regulatory
      strategies less than the other groups, also differing from resistant infants in
      their greater use of object regulatory strategies. There were no significant
      differences as regards self-comforting regulation. Thus, the findings showed how
      the most significant differences to emerge between the groups concerned hetero
      regulatory strategies, developed by the infant in interaction with attachment
      figures, and regulatory strategies oriented towards objects. Further analysis
      showed how the use by part of each attachment group of the emotion regulation
      strategies varies, differentiating the episodes of the SSP according to their
      level of stress.

PMID- 21195478
TI  - L2pB1: a new player in autoimmunity.
AB  - L2pB1 cells (PD-L2positive B1 cells) are a newly discovered subpopulation of B1 B
      cells. L2pB1 cells are noted for the expression of PD-L2 (CD273, B7-DC), a ligand
      for the inhibitory receptor PD-1, which distinguishes this subpopulation from
      other B1 B cells that lack PD-L2, namely, L2nB1 cells (PD-L2negative B1 cells).
      PD-L2 gene expression is regulated differently in B1 B cells as compared to
      macrophages and dendritic cells. L2pB1 cells share many commonly known B1 cell
      features with L2nB1 cells. These include spontaneous IgM secretion, constitutive
      ERK activation, elevated co-stimulatory molecule expression, skewing of T cell
      differentiation, and unique proliferative responsiveness (to LPS, PMA, but not
      anti-IgM). However, L2pB1 cells express a biased Ig repertoire that is enriched
      for self-reactivity as compared with L2nB1 cells. Further, L2pB1 cells present
      antigen more potently than L2nB1 cells. In addition, L2pB1 cells switch Ig
      isotype more readily from IgM to IgG1 and IgG2b upon cytokine stimulation.
      Moreover, increased numbers of L2pB1 cells are present in murine models of lupus
      and this correlates with increased serum anti-dsDNA titers. These characteristics
      suggest that L2pB1 cells may play a pathophysiological role in autoimmune
      dyscrasias. In this report we review the special features of L2pB1 cells and how
      they may contribute to autoimmunity.

PMID- 21195480
TI  - Young infants' eye movements over "natural" scenes and "experimental" scenes.
AB  - Eye movements of 30 4-month-olds were tracked as infants viewed animals and
      vehicles in "natural" scenes and, for comparison, in homogeneous "experimental"
      scenes. Infants showed equivalent looking time preferences for natural and
      experimental scenes overall, but fixated natural scenes and objects in natural
      scenes more than experimental scenes and objects in experimental scenes and
      shifted fixations between objects and contexts more in natural than in
      experimental scenes. The findings show how infants treat objects and contexts in
      natural scenes and suggest that they treat more commonly used experimental scenes
      differently.

PMID- 21195481
TI  - From putative genes to temperament and culture: cultural characteristics of the
      distribution of dominant affective temperaments in national studies.
AB  - BACKGROUND: Affective temperaments may carry distinct evolutionary advantages
      both on the individual or a group level, so we can expect that in different
      cultural and national samples the frequency of dominant affective temperaments
      will show characteristic differences. The aim of the present study was to
      investigate the characteristics of distribution of dominant affective
      temperaments in different national studies of general non-clinical population.
      METHOD: In our study we included six studies published in different countries
      around the world (Argentina, Germany, Hungary, Korea, Portugal, and Lebanon)
      which investigated a large sample of non-clinical population using TEMPS-A, and
      reported frequencies for dominant affective temperaments. The frequencies of
      dominant affective temperaments were compared using chi square tests. RESULTS: We
      found a significant difference in the frequency of affective temperaments among
      the different national studies in case of the cyclothymic, hyperthymic and
      irritable temperaments. CONCLUSIONS: We found important parallels between the
      frequency of affective temperaments and cultural dimensions described by Hofstede
      (Hofstede and Hofstede, 2005). The characteristics encompassed by the depressive
      temperament show considerable similarities with Hofstede's individualism
      collectivism dimension, while those of the hyperthymic temperament seem to be
      similar to uncertainty avoidance, and the irritable temperament shows
      similarities with Hofstede's power distance. Furthermore, the relative frequency
      of these dominant temperaments in case of the different national samples
      paralleled the relative scores of these countries on the corresponding cultural
      scales. Our results indicate an important relationship between affective
      temperaments and cultural dimensions, which suggests that these phenomena may be
      the manifestations of the same genetically determined predispositions in
      different forms. LIMITATION: We included a study by Erfurth et al. (2005), in
      which affective temperaments were evaluated using the TEMPS-M. Also, in the
      Korean study the Korean version of the TEMPS-A was not validated.

PMID- 21195482
TI  - Differences between bipolar I and bipolar II disorders in clinical features,
      comorbidity, and family history.
AB  - BACKGROUND: The present study was designed to investigate whether bipolar II
      disorder (BP-II) has different characteristics from bipolar I disorder (BP-I),
      not only in manic severity but also in clinical features, prior course,
      comorbidity, and family history, sufficiently enough to provide its nosological
      separation from BP-I. METHODS: Comprehensive clinical evaluation was performed
      based on information available from ordinary clinical settings. Seventy-one BP-I
      and 34 BP-II patients were assessed using the Diagnostic Interview for Genetic
      Studies, Korean version. Psychiatric assessment for first-degree relatives
      (n=374) of the probands was performed using the modified version of the Family
      History-Research Diagnostic Criteria. RESULTS: The frequency of depressive
      episodes was higher in BP-II (p=0.009) compared to BP-I. Further, seasonality
      (p=0.035) and rapid-cycling course (p=0.062) were more common in BP-II. Regarding
      manic expression, 'elated mood' was predominant in BP-II whereas 'elated mood'
      and 'irritable mood' were equally prevalent in BP-I. With regard to depressive
      symptoms, psychomotor agitation, guilty feeling, and suicidal ideation were more
      frequently observed in BP-II. BP-II patients exhibited a higher trend of lifetime
      co-occurrence of an axis I diagnosis (p=0.09), and a significantly higher
      incidence of phobia and eating disorder. The overall occurrence rate of
      psychiatric illness in first-degree relatives was 15.4% in BP-I and 26.5% in BP
      II (p=0.01). Major depression (p=0.005) and substance-related disorder (p=0.051)
      were more prevalent in relatives of BP-II probands. CONCLUSION: Distinctive
      characteristics of BP-II were identified in the current study and could be
      adopted to facilitate the differential diagnosis of BP-I and BP-II in ordinary
      clinical settings.

PMID- 21195483
TI  - Chronic posttraumatic stress and its predictors in patients living with an
      implantable cardioverter defibrillator.
AB  - INTRODUCTION: Patients with an implantable cardioverter defibrillator (ICD) show
      clinically relevant depression and anxiety, but little is known about their
      levels of posttraumatic stress. We assessed chronic posttraumatic stress
      attributable to a traumatic cardiac event and its predictors in patients at two
      time points after ICD placement. METHODS: We investigated 107 consecutively
      enrolled patients (57 +/- 14 years, 62% men) on average 24 +/- 21 months after
      ICD placement (baseline) and again 41 +/- 18 months later (follow-up). All
      patients completed the Impact of Event Scale-Revised (IES-R) to self-rate the
      severity of posttraumatic stress (range 0-110). The 30% of patients with the
      highest IES-R scores (>= 25) at baseline were defined as PTSD cases; the same
      threshold was applied to define PTSD caseness at follow-up. RESULTS:
      Posttraumatic stress increased from baseline to follow-up (19 +/- 22 vs. 25 +/-
      19, p < 0.001); 19% of patients had PTSD at both assessments, 12% at baseline
      only, and 18% at follow-up only. Female gender as well as greater peritraumatic
      dissociation and depression predicted greater posttraumatic stress at baseline (p
      values <= 0.041). Greater baseline posttraumatic stress, helplessness,
      alexithymia, and >= 5 shocks during follow-up all predicted greater posttraumatic
      stress at follow-up (p-values <= 0.029). Female gender, helplessness, and
      depression predicted PTSD at baseline (p-values <= 0.022); low education and
      posttraumatic stress at baseline predicted PTSD at follow-up (p-values <= 0.003).
      CONCLUSIONS: Between 2 and 5.5 years post-ICD placement chronic posttraumatic
      stress slightly increased and nearly one-fifth of patients had newly developed
      PTSD. The identified psychological predictors of long-term chronicity of
      posttraumatic stress might particularly inform behavioral interventions for ICD
      recipients.

PMID- 21195484
TI  - Objective physical functioning in patients with depressive and/or anxiety
      disorders.
AB  - BACKGROUND: Poorer physical function in patients with depressive or anxiety
      disorders has been reported, but is often measured by self-reports which may be
      biased by mood. This study examined the association between depression and
      anxiety and physical function using objective measures in a large cohort, and
      investigated which psychiatric characteristics are associated with physical
      function. METHODS: Baseline data from the Netherlands Study of Depression and
      Anxiety were used, including persons with current depressive and/or anxiety
      disorders (n = 1629) and healthy controls without lifetime diagnoses (n = 629).
      Psychiatric characteristics studied included type of disorder, duration,
      severity, age of onset, and antidepressant use. Hand grip strength and lung
      function were used as general objective measurements of physical function.
      RESULTS: Women with depressive or anxiety disorders had significantly poorer
      physical function - both lower grip strength and lung function - compared to
      healthy controls, especially those with a late age of onset (>= 40 years). Poorer
      lung function was present among the women using antidepressants, those with
      higher symptom severity, and those with depression compared to anxiety disorder.
      In men, depressive or anxiety disorder was associated with better lung function
      but not with hand grip strength. LIMITATIONS: Due to the cross-sectional design
      no causal relationships could be established. CONCLUSIONS: In women, depressive
      or anxiety disorders were associated with objective indicators of poorer physical
      function. Since this association was most pronounced for later onset disorders,
      it suggests a larger role of physical function in depressive and anxiety
      disorders at later age.

PMID- 21195485
TI  - Reduced physiologic complexity is associated with poor sleep in patients with
      major depression and primary insomnia.
AB  - BACKGROUND: Depression is known to be associated with altered cardiovascular
      variability and increased cardiovascular comorbidity, yet it is unknown whether
      altered cardiac autonomic function in depression is associated with insomnia, a
      common symptom comorbid with depression. This study aimed to investigate the long
      term diurnal profile of autonomic function as measured by heart rate variability
      (HRV) in both major depression and primary insomnia patients. METHOD: A total of
      52 non-medicated patients with major depression, 47 non-medicated patients with
      primary insomnia, and 88 matched controls without insomnia were recruited. Each
      subject was assessed by means of sleep and mood questionnaires and underwent
      twenty-four-hour ambulatory electrocardiogram monitoring. Standard HRV analysis
      and a well-validated complexity measure, multiscale entropy, were applied to
      comprehensively assess the diurnal profiles of autonomic function and physiologic
      complexity in our study sample. RESULTS: Compared with the controls, the patients
      with major depression and those with primary insomnia exhibited significant
      reductions in parasympathetic-related HRV indices, and this association was
      mainly driven by the presence of poor sleep. Both groups of patients also
      exhibited significant reductions in physiologic complexity during the sleep
      period as compared with the healthy controls. Alterations in HRV indices were
      correlated with perceived sleep questionnaire scores but not with depression
      scales. CONCLUSIONS: Our findings suggest a pivotal role of sleep disturbance in
      regulating cardiovascular variability in major depression and primary insomnia
      patients. These findings could highlight the importance of treating insomnia as
      an independent disease rather than a symptom.

PMID- 21195486
TI  - Effectiveness of olanzapine monotherapy and olanzapine combination treatment in
      the long term following acute mania--results of a two year observational study in
      bipolar disorder (EMBLEM).
AB  - BACKGROUND: This study compared the 2-year outcomes of patients with a
      manic/mixed episode of bipolar disorder taking olanzapine monotherapy or
      olanzapine in combination with other agents. METHODS: EMBLEM (European Mania in
      Bipolar Longitudinal Evaluation of Medication) is a 2-year, prospective,
      observational study of clinical and functional outcomes of bipolar patients with
      an index manic/mixed episode. The study consisted of two phases: acute (12 weeks)
      and maintenance (follow-up over 2 years). The longitudinal outcome measure was
      the Clinical Global Impression-Bipolar Disorder scale. Cox regression models
      compared outcomes of both therapy groups using intention-to-treat and switching
      medication analysis. Treatment-emergent adverse events were also assessed.
      RESULTS: 1076 patients were included in this analysis. 29% took olanzapine as
      monotherapy (n = 313) and 71% as combination (n = 763) at 12-weeks post-baseline
      (end of study acute phase). After adjusting for patient characteristics using
      switching medication analysis, only relapse rates differed (p = 0.01) in favour
      of monotherapy-treated patients. There was no significant difference in rates of
      improvement, remission, and recovery. Patients treated with combination therapy
      reported more tremor (OR 2.37, 95%CI 1.44-3.89) and polyuria (OR 3.08, 95%CI 1.45
      6.54) treatment-emergent events than monotherapy, although weight change was
      greater in the monotherapy group. LIMITATIONS: Unknown confounding and potential
      selection bias may differentially impact treatment outcomes. CONCLUSIONS: EMBLEM
      patients benefitted from the selected therapy to a similar extent. Differences in
      patient characteristics between those prescribed monotherapy and combination
      therapy appear to be clinically relevant in the treatment decision. Physicians
      must balance the benefits and risks when determining appropriate treatment for
      individual patients.

PMID- 21195487
TI  - Associations linking parenting styles and offspring personality disorder are
      moderated by parental personality disorder, evidence from China.
AB  - The aim of the study is to examine the association linking parenting and
      personality disorder controlling for parental personality disorder, and whether
      this association is moderated by parental PD. Data were from community-dwelling
      high school students aged 18 and above and their parents living in Beijing,
      China. A total of 181 cases and 2,605 controls were included in this study.
      Personality disorder in students was assessed via a two-stage approach,
      Personality Diagnostic Questionnaire as a screening tool and International
      Personality Disorder Examination as the diagnostic tool. Information about
      parenting was collected from students using Egna Minnen av. Betraffande
      Uppfostran. Negative parenting styles, e.g. rejective or over-protective
      parenting, were found to be associated with the occurrence of personality
      disorder. Conflictive parenting styles were also found to be associated with
      personality disorder. Generally stronger associations were found for students
      with parental personality disorder as compared to students without parental
      personality disorder. Findings from this study support the role of parenting in
      the occurrence of PD, especially for children with family history of personality
      disorder.

PMID- 21195488
TI  - Selected human leukocyte antigen class II polymorphisms and risk of adult glioma.
AB  - Few studies have examined the relationship between human leukocyte antigen (HLA)
      polymorphisms and adult glioma, particularly at class II loci. We evaluated the
      association between selected HLA class II polymorphisms and adult glioma in a
      large, hospital-based case-control study, using unconditional logistic
      regression. DQB1 06 (OR=1.67, 95% CI=1.17-2.39) and DRB1 13 (OR=1.69, 95% CI=1.08
      2.64) alleles were associated with an increased risk of glioma, while the DQB1 05
      allele showed an inverse association (OR=0.63, 95% CI=0.43-0.93). These results,
      which were of borderline significance once controlled for the false discovery
      rate, suggest a potential role for the DQB1 06, DQB1 05, and DRB1 13 alleles in
      glioma susceptibility.

PMID- 21195489
TI  - Duration of preceding hypertension is associated with prolonged length of ICU
      stay.
AB  - BACKGROUND: A substantial proportion of patients suffer prolonged length of
      intensive care unit stay (PLOS) or prolonged mechanical ventilation (PMV)
      following coronary artery bypass grafting (CABG). Identifying factors associated
      with PLOS and PMV would aid in patient risk stratification. We sought to identify
      the factors associated with PLOS and PMV following CABG. METHODS: Participants
      were patients undergoing first-time elective CABG. All were observed until
      discharge and clinical data were collected on a standardized proforma. PLOS and
      PMV were defined a priori as >2 days and >12 h respectively, based on centre
      norms. RESULTS: Of the 439 patients in the study, 105 (23.9%) had PLOS and 111
      (25.2%) had PMV. Independent predictors of PMV were age, diabetes, previous
      myocardial infarction (MI), New York Heart Association (NYHA) class and statin
      use. The only independent predictor of PLOS was the duration of preceding
      hypertension. CONCLUSION: The factors associated with PMV and PLOS in our study
      are easily attainable, routine clinical details and may be built into bed
      management algorithms. Confirmation of the association of preceding hypertension
      and subsequent investigation of the possible mechanism mediating this
      association, is suggested.

PMID- 21195490
TI  - Telemedicine for diagnosing and managing paroxysmal atrial fibrillation in
      outpatients. The phone in the pocket.
AB  - BACKGROUND: Individuals who experience paroxysmal atrial fibrillation (PAF) are
      at risk of serious sequelae, including stroke. PAF episodes usually occur in out
      of-hospital settings, and patients seek emergency services for differential
      diagnosis and treatment. METHODS: Medical records of all subscribers to a
      telemedical system ('SHL'-Telemedicine) who had one or more episodes of recurrent
      PAF managed by the call center between 2/2002 and 8/2009 were retrieved.
      Treatment protocol consisted of initial electrocardiographic confirmation of PAF
      and repeat electrocardiograms within 24h. Management was exclusively by
      telephonically transmitted recommendations (Group A) or also included
      intervention by the attending physician of a 'SHL'-Telemedicine mobile intensive
      care unit (Group B). RESULTS: A total of 649 cardiac patients (1886 PAF episodes)
      were enrolled. The leading complaint was palpitation (57%). The 576 Group A
      patients had 1667 objectively documented PAF episodes, of which 1326 (79.5%) were
      converted into sinus rhythm by following telephonically delivered instructions.
      Their mean heart rate decreased from 85+/-15 to 66+/-10beats per minute (bpm)
      (P<0.001). Heart rate remained unchanged (86+/-15bpm) for those who remained in
      PAF. The 160 Group B patients (218 PAF episodes) had a conversion rate of 70%
      (153/218). The heart rate in converted cases decreased from 92+/-24bpm to 68+/
      21bpm compared to a decrease from 90+/-21bpm to 87+/-21bpm in non-converted cases
      (P<0.001). CONCLUSIONS: Telemedicine for rapid out-of-hospital diagnosis and
      provision of objective documentation and instructions for appropriate management
      of PAF is feasible and could avoid potential PAF-associated complications and
      unnecessary emergency room visits and hospitalizations.

PMID- 21195491
TI  - Positive predictive value of computed tomography coronary angiography in clinical
      practice.
AB  - BACKGROUND: Several studies have investigated the diagnostic performance of
      computed tomography coronary angiography (CTCA) for the detection of significant
      coronary artery disease (CAD). These studies were performed in patients that were
      already referred for invasive coronary angiography (ICA) and prevalence of
      significant CAD was high. Although the negative predictive value of CTCA was
      consistently high, a wide range of positive predictive values (PPVs) was
      reported. Thus, the PPV of CTCA in patients that undergo CTCA as part of a
      clinical diagnostic evaluation remains unclear. This study investigated the PPV
      of CTCA for the detection of significant CAD in clinical practice. METHODS: A
      total of 181 patients with low to intermediate pre-test probability CAD that were
      referred for non-invasive evaluation of chest pain underwent 64-slice CTCA. CTCA
      was scored per segment as normal, non-obstructive CAD or obstructive CAD (>50%
      diameter stenosis). All patients with obstructive CAD according to CTCA,
      underwent ICA. Significant CAD was defined as >50% diameter stenosis on ICA.
      RESULTS: According to CTCA, 65 (35.9%) patients had obstructive CAD. In 26
      (14.4%) patients, significant CAD was found by ICA. The PPV for detection of
      significant CAD per patient, per vessel and per segment were 40.0% (26/65, 95%
      CI: 30.6-50.2%), 31.3% (36/115, 95% CI: 24.7-38.8%) and 25.5% (42/165; 95% CI:
      20.3-31.4%), respectively. CONCLUSIONS: The PPV of CTCA for detection of
      significant CAD in patients with low to intermediate probability CAD that are
      clinically referred for non-invasive evaluation of chest pain is markedly lower
      than generally reported.

PMID- 21195492
TI  - Assessing biosecurity practices, movements and densities of poultry sites across
      Belgium, resulting in different farm risk-groups for infectious disease
      introduction and spread.
AB  - The existing diversity within poultry systems affects the potential risk of
      infectious disease introduction and spread. Population data on the level of
      biosecurity and between-farm contacts is scarce, despite its importance for
      identifying possible routes of disease transmission. A study was carried out in
      Belgium to investigate and differentiate professional and hobby poultry sites
      based on their biosecurity levels and farm movements. Questionnaire data from a
      total of 37 professional poultry farms, 19 hatcheries and 286 hobby poultry sites
      were analyzed using a combination of a linear scoring system, a Categorical
      principal component analysis (CATPCA) and a Two-Step cluster analysis (TSCA). In
      general, the level of biosecurity was lower in hobby poultry flocks, mainly due
      to the poor confinement against the outdoor environment and the poor
      infrastructural hygiene. Most Belgian professional poultry farms and hatcheries
      had an acceptable level of adoption of standard biosecurity practices, however
      less attention was given to the way transportation vehicles and employers were
      brought onto farms and professional visitors welcomed. Considerable variation in
      the movements and in the structure of the networks arising from these movements
      was found. Movement frequencies were higher at professional farms compared to
      hobby farms. Results showed that multiple category farming systems had the
      highest total movement frequencies. Monthly frequencies of professional visits
      often exceeded those of poultry and egg movements. Professional and hobby poultry
      sites were also connected, but movements of poultry and eggs were found only to
      occur from professional to hobby sites. However, hobby poultry keepers were
      personally purchasing the poultry and eggs on the professional poultry sites. Six
      groups of poultry sites were differentiated, which are interpreted as very low to
      very high risk groups, based on the potential of infectious disease introduction
      and spread.

PMID- 21195493
TI  - Association between lean meat percentage and average daily weight gain in Danish
      slaughter pigs.
AB  - Danish pigs that are within optimal weight limits and have a high lean meat
      percentage (LMP) obtain the best prices at slaughter. Another reason to consider
      the variation in LMP is the assumed association between LMP and average daily
      weight gain (ADG) at the individual level. The aim of this study was to test
      whether high ADG was associated with low LMP and vice versa. A cohort of 99 pigs
      from a conventional Danish herd was followed from 30kg to slaughter. The data
      included days in the herd, start- and end-weights, calculated ADG and LMP,
      reported from the abattoir. The study also included existing data from 13,057
      boars from a Danish boar test station. The results of the study demonstrated a
      significant negative association between LMP and ADG: Pearson's correlation
      coefficient (r)=-0.42 (95% CI: -0.57; -0.24) (p<0.0001) for the cohort and r=
      0.42 (95% CI: -0.48; -0.36) (p<0.0001) for the boars.

PMID- 21195494
TI  - Do bad report cards have consequences? Impacts of publicly reported provider
      quality information on the CABG market in Pennsylvania.
AB  - Since 1992, the Pennsylvania Health Care Cost Containment Council (PHC4) has
      published cardiac care report cards for coronary artery bypass graft (CABG)
      surgery providers. We examine the impact of CABG report cards on a provider's
      aggregate volume and volume by patient severity and then employ a mixed logit
      model to investigate the matching between patients and providers. We find a
      reduction in volume of poor performing and unrated surgeons' volume but no effect
      on more highly rated surgeons or hospitals of any rating. We also find that the
      probability that patients, regardless of severity of illness, receive CABG
      surgery from low-performing surgeons is significantly lower.

PMID- 21195495
TI  - Diagnosing fatigue in gait patterns by support vector machines and self
      organizing maps.
AB  - The aim of the study was to train and test support vector machines (SVM) and self
      organizing maps (SOM) to correctly classify gait patterns before, during and
      after complete leg exhaustion by isokinetic leg exercises. Ground reaction forces
      were derived for 18 gait cycles on 9 adult participants. Immediately before the
      trials 7-12, participants were required to completely exhaust their calves with
      the aid of additional weights (44.4+/-8.8kg). Data were analyzed using: (a) the
      time courses directly and (b) only the deviations from each individual's
      calculated average gait pattern. On an inter-individual level the person
      recognition of the gait patterns was 100% realizable. Fatigue recognition was
      also highly probable at 98.1%. Additionally, applied SOMs allowed an alternative
      visualization of the development of fatigue in the gait patterns over the
      progressive fatiguing exercise regimen.

PMID- 21195496
TI  - Improving the storage stability of Bifidobacterium breve in low pH fruit juice.
AB  - Bifidobacterial food applications are limited since bifidobacteria are sensitive
      to e.g. acidic conditions prevalent in many food matrices. The aim of the present
      study was to investigate whether a low pH selection step alone or combined to UV
      mutagenesis could improve the viability of an acid sensitive Bifidobacterium
      strain, B. breve 99, in low pH food matrices. Furthermore, the potential of
      carriers and an oat fibre preparation to further improve the stability was
      studied. The best performing low pH tolerant variants in the present study were
      generated by UV-mutagenesis with 70-700MUJ/cm(2) followed by incubation in growth
      medium at pH 4.5. The most promising variants regarding the low pH tolerance
      showed, in repeated tests with cells grown without pH control, about one Log
      value better survival in pH 3.8 fruit juice after one week storage at 4 degrees C
      compared to wild-type B. breve 99. Cells grown with pH control, PDX formulated
      and then frozen showed poorer viability in low pH fruit juice than cells grown
      with no pH control. For frozen concentrates pH 3.8 was too stressful and no or
      small differences between the variants and the wild-type strain were seen. The
      differences detected at pH 3.8 with the cells grown without pH control were also
      seen with the frozen concentrates at pH 4.5. Some improvement in the stability
      could be achieved by using a combination of trehalose, vitamin C and PDX as a
      freezing carrier material, whereas a significant improvement in the stability was
      seen when oat fibre was added into the fruit juice together with the frozen
      cells. Due to the initial very poor fruit juice tolerance of B. breve 99 the
      obtained improvement in the stability was not enough for commercial applications.
      However, the same methods could be applied to initially better performing strains
      to further improve their stability in the fruit juice.

PMID- 21195497
TI  - Ustilago maydis killer toxin as a new tool for the biocontrol of the wine
      spoilage yeast Brettanomyces bruxellensis.
AB  - Brettanomyces bruxellensis is one of the most damaging species for wine quality,
      and tools for controlling its growth are limited. In this study, thirty-nine
      strains belonging to Saccharomyces cerevisiae and B. bruxellensis have been
      isolated from wineries, identified and then tested against a panel of thirty-nine
      killer yeasts. Here, for the first time, the killer activity of Ustilago maydis
      is proven to be effective against B. bruxellensis. Mixed cultures in winemaking
      conditions show that U. maydis CYC 1410 has the ability to inhibit B.
      bruxellensis, while S. cerevisiae is fully resistant to its killer activity,
      indicating that it could be used in wine fermentation to avoid the development of
      B. bruxellensis without undesirable effects on the fermentative yeast. The
      characterization of the dsRNAs isolated and purified from U. maydis CYC 1410
      indicated that this strain produces a KP6-related toxin. Killer toxin extracts
      were active against B. bruxellensis at pH values between 3.0 and 4.5 and
      temperatures comprised between 15  degrees C and 25  degrees C, confirming their
      biocontrol activity in winemaking and wine aging conditions. Furthermore, small
      amounts (100 AU/ml) of killer toxin extracts from U. maydis significantly reduced
      the amount of 4-ethylphenol produced by B. bruxellensis, indicating that in
      addition to the growth inhibition observed for high killer toxin concentrations
      (ranging from 400 to 2000 AU/ml), small amounts of the toxin are able to reduce
      the production of volatile phenols responsible for the aroma defects in wines
      caused by B. bruxellensis.

PMID- 21195498
TI  - Antifumonisin activity of natural phenolic compounds A structure-property
      activity relationship study.
AB  - Fumonisin B(1) (FB(1)) is a Fusarium mycotoxin that has received considerable
      attention from food regulatory agencies, since it shows immunotoxic, neurotoxic,
      hepatotoxic, nephrotoxic and carcinogenic properties in animals. Although several
      publications have reported that some natural phenolic compounds can cause a
      reduction in mycotoxin production, little is known about the molecular properties
      related to their antitoxigenic activities. The objective of this work was to
      evaluate which of these molecular properties are important in antifumonisin
      activity, with this being the first structure-activity relationship study
      concerning the antimyctoxigenic activity of natural phenolic compounds. The
      results of the experimental determination of the FB(1) inhibition capacity for
      ten natural phenolic compounds revealed thymol, carvacrol, and isoeugenol
      followed by eugenol to be the most active antifumonisin compounds. Lipophilicity,
      molar refractivity and saturated area were demonstrated to be the molecular
      properties or descriptors which best explained the antifumonisin activity of
      these phenolic compounds. A mathematical expression, obtained by QSAR analysis,
      was able to predict the antifumonisin activity of other structurally related
      molecules. These findings could provide an important contribution in the search
      for new compounds with antifumonisin activity.

PMID- 21195499
TI  - Biosorption of copper by wine-relevant lactobacilli.
AB  - Must and wine may be contaminated with elevated copper concentrations by the use
      of fungicides or in course of the vinification process. Hitherto only a few
      practicable and harmless procedures exist to reduce an excess of copper from must
      and wine. For this reason we investigated the biosorption of copper by eight wine
      relevant Lactobacillus species. Both, living and heat-inactivated cells revealed
      a significant degree of Cu adsorption. It was shown that Cu binding correlated
      positively with an increasing pH value of the environment. The highest binding
      capacity of the tested lactic acid bacteria was found for L. buchneri DSM 20057
      with a maximum of 46.17 MUg Cu bound per mg cell in deionized water. In must,
      wine and grape juice Cu was removed less effective which is not solely attributed
      to low pH-values, but also to specific medium parameters such as intrinsic metal
      cations, organic acids or phenolic compounds. Nevertheless, about 0.5-1.0 MUg Cu
      per ml could be removed from wine samples, which is sufficient enough to lower
      critical copper concentrations.

PMID- 21195500
TI  - Mycetozoal bloom in a hydroponic culture of garden cress (Lepidium sativum L.).
AB  - The role and importance of the true slime moulds (mycetozoans, Mycetozoa,
      formerly Myxomycetes) for agriculture and food industry are poorly documented,
      most probably because of a low popularity of these "macroscopic microorganisms"
      among researchers in the past. Here we report probably for the first time the
      massive occurrence of true slime moulds in their vegetative, plasmodial form in a
      product intended for direct consumption, i.e. in a household hydroponic culture
      of garden cress (Lepidium sativum L.). The plasmodia gradually produced numerous,
      stalked or sessile sporangia and plasmodiocarps, which made it possible to
      identify them as Didymium species complex (the stalked sporangia) and Didymium
      difforme (Pers.) Gray (the sessile sporangia and plasmodiocarps). The mycetozoans
      were transferred to in vitro culture where they were maintained for several weeks
      on oat flour. We briefly discuss the importance of this observation from the
      point of view of biochemical interactions between the plant and the true slime
      moulds in a general context of slime mould biology. Our observation indicates
      that the presence of mycetozoan material in food products may be frequent, while
      its influence on food safety and quality remains unknown.

PMID- 21195501
TI  - Self-reported experience of hypoglycemia among adults with type 2 diabetes
      mellitus (Exhype).
AB  - AIMS: To evaluate the experience of hypoglycemia in patients treated with
      metformin in combination with sulphonylureas (SUs) and the impact on patients'
      quality of life (QoL) and worry about hypoglycemia. METHODS: This was a national,
      cross-sectional, multicenter study. Patients with type 2 diabetes treated with
      metformin and SU dual therapy were recruited by 54 investigators between January
      2009 and August 2009. The patients were asked to complete a QoL instrument, the
      EuroQol-5 Dimensions questionnaire (EQ-5D), and the Hypoglycemia Fear Survey (HFS
      II). Investigators completed a web-based case report form on laboratory values,
      medical history and anti-diabetic treatment. RESULTS: A total of 430 patients
      (60% male) were included in the study. Mean age was 69 years. Approximately one
      fifth of the patients experienced moderate or worse symptoms of hypoglycemia.
      Patients who experienced moderate or worse hypoglycemia had lower QoL as measured
      by the weighted EQ-5D summary score (0.81 vs. 0.88; p<0.001) than patients who
      experienced mild or no hypoglycemia. CONCLUSIONS: Experience of hypoglycemia was
      found to be associated with lower QoL in patients with type 2 diabetes on dual
      treatment with metformin and sulphonylurea. This should be taken into
      consideration when selecting treatment for these patients in clinical practice.

PMID- 21195502
TI  - Worldwide violence against women legislation: an equity approach.
AB  - OBJECTIVES: To describe the recommendations and interventions addressing violence
      against women (VAW) in vulnerable women (disabled, pregnant, ethnic minority,
      immigrant and older women) in key documents and laws enacted in different
      countries. METHODS: Content analysis of key documents for the development of VAW
      policies and laws: The United Nations Handbook for Legislation on Violence
      Against Women Advance Version, the Model of Laws and Policies on Intrafamiliar
      Violence Against Women of the Pan-American Health Organization and Recommendation
      No. R(2002)5 of the Committee of Ministers of the European Council. The content
      of the 62 VAW laws was also analyzed. RESULTS: Key documents demonstrate the
      importance of eliminating any obstacle facing disabled, pregnant, immigrant,
      ethnic minority or older women when accessing VAW services. Only 12 laws mention
      one or more of these groups of vulnerable women. Pregnant, disabled and ethnic
      minority women are the groups most often mentioned. In these laws, references to
      punitive measures, action plans and specific strategies to guarantee access to
      VAW resources are the most common interventions. CONCLUSION: Decisive
      interventions addressing the specific needs of disabled, pregnant, immigrant,
      ethnic minority and older women are needed in order to achieve a broader equity
      approach in VAW legislation.

PMID- 21195503
TI  - Multivariate Bayesian modeling of known and unknown causes of events--an
      application to biosurveillance.
AB  - This paper investigates Bayesian modeling of known and unknown causes of events
      in the context of disease-outbreak detection. We introduce a multivariate
      Bayesian approach that models multiple evidential features of every person in the
      population. This approach models and detects (1) known diseases (e.g., influenza
      and anthrax) by using informative prior probabilities and (2) unknown diseases
      (e.g., a new, highly contagious respiratory virus that has never been seen
      before) by using relatively non-informative prior probabilities. We report the
      results of simulation experiments which support that this modeling method can
      improve the detection of new disease outbreaks in a population. A contribution of
      this paper is that it introduces a multivariate Bayesian approach for jointly
      modeling both known and unknown causes of events. Such modeling has general
      applicability in domains where the space of known causes is incomplete.

PMID- 21195504
TI  - Association of genetic polymorphisms in DNA repair pathway genes with non-small
      cell lung cancer risk.
AB  - DNA repair function is believed to play an important role in cancer development
      and to be affected by genetic polymorphisms. Numerous epidemiological studies
      have examined the associations between single nucleotide polymorphisms (SNPs) in
      the DNA repair genes and lung cancer risk, but the results are inconsistent. The
      aim of this study was to investigate the associations of several SNPs in the DNA
      repair pathways and risk of non-small cell lung cancer (NSCLC) in a Chinese
      population. The study included 581 NSCLC cases and 603 healthy controls. The
      polymorphisms studied include XRCC1 (rs25487), hOGG1 (rs1052133), MUTYH
      (rs3219489) in the base excision repair (BER) pathway, XPA (rs1800975), ERCC2
      (rs1799793 and rs13181) in the nucleotide excision repair (NER) pathway and XRCC3
      (rs861539) in the double strand break repair (DSB) pathway. The associations
      between lung cancer risk and genetic polymorphisms were evaluated using the
      logistic regression models and subgroup analyses. Meta-analyses were conducted
      for the SNPs shown to be significantly associated with lung cancer risk in our
      study. Our findings showed that XPA -4G>A (rs1800975) had a significant
      association with lung cancer (OR=1.64; 95% CI: 1.03-2.60), and the association
      was more evident in squamous cell carcinoma (OR=1.69; 95% CI: 1.00-2.84). Three
      BER polymorphisms showed no independent effects on the risk of lung cancer. The
      stratified analysis showed higher lung cancer risk among the smokers carrying the
      variant XPA allele (OR=1.75; 95% CI: 1.15-2.65) and among the non-smokers
      carrying the variant ERCC2 allele of 312Asn (OR=2.10; 95% CI: 1.22-3.64). Meta
      analysis showed that individuals with the variant AA genotype of XPA (-4G>A) had
      higher risk of lung cancer compared to those with the 'G' wild allele (OR=1.28;
      95% CI: 1.12-1.47); and those with variant alleles of ERCC2 312Asn had higher
      risk compared to those with wild 312Asp alleles among nonsmokers (OR=1.58; 95%
      CI: 1.20-2.08). Although smoking is the dominant risk factor of lung cancer, XPA 
      4G>A (rs1800975) is also associated with the risk of NSCLC, especially for
      squamous cell carcinoma, among Asian young smokers. ERCC2 Asp/Asn (rs1799793)
      polymorphism may also affect lung cancer risk among nonsmokers. The NER pathway
      seems to have more strong influences on lung cancer than the BER pathway.

PMID- 21195505
TI  - Dark diversity: shedding light on absent species.
AB  - Ecological theory and nature conservation have traditionally relied solely on
      observed local diversity. In this review, we recommend including those species
      that are absent from an ecosystem but which belong to its species pool; that is,
      all species in the region that can potentially inhabit those particular
      ecological conditions. We call the set of absent species 'dark diversity'.
      Relating local and dark diversities enables biodiversity comparisons between
      regions, ecosystems and taxonomic groups, and the evaluation of the roles of
      local and regional processes in ecological communities. Dark diversity can also
      be used to counteract biodiversity loss and to estimate the restoration potential
      of ecosystems. We illustrate the dark diversity concept by globally mapping plant
      dark diversity and the local:dark diversity ratio.

PMID- 21195506
TI  - Stable transformation of Mesembryanthemum crystallinum (L.) with Agrobacterium
      rhizogenes harboring the green fluorescent protein targeted to the endoplasmic
      reticulum.
AB  - Stable transformation of Mesembryanthemum crystallinum L. (common ice plant) with
      a green fluorescent protein (GFP) construct targeted to the endoplasmic reticulum
      was obtained. Seven and fourteen days after germination seedlings were infected
      with Agrobacterium rhizogenes strain ARqua1 either by direct coating of the cut
      radicles with bacteria growing on solid medium or by immersion of the cut surface
      in bacterial suspension at different optical densities. Both methods of infection
      resulted in production of GFP-positive roots with a frequency ranging from 6 to
      20% according to the age of the explants and the application procedure. The green
      fluorescing roots displayed the typical hairy root phenotype and were easily
      maintained in liquid medium without growth regulators for over 2 years. Stable
      expression of the transgene in the roots was confirmed by polymerase chain
      reaction (PCR), immunoblotting and the capacity of roots to grow and produce
      callus on kanamycin-enriched medium. Nineteen endogenous cytokinins were
      determined in transgenic and non-transformed roots. The results revealed
      significantly lower levels of the free bases of isopentenyladenine,
      dihydrozeatin, cis- and trans-zeatin, as well as a conspicuous decline in
      concentrations of the corresponding nucleosides and most nucleotides in
      transgenic roots compared to the wild type. Comparison of the cytokinin profiles
      in transgenic and non-transformed roots suggested that transformation by A.
      rhizogenes disturbed cytokinin metabolism during the early steps of biosynthesis.
      Calli obtained from transformed roots were GFP-positive and remained non
      regenerative or displayed high rhizogenic potential depending on the
      auxin/cytokinin ratio in the medium. Calli and callus-derived roots showed a
      strong GFP signal for over 2 years.

PMID- 21195507
TI  - [We can and must improve hand hygiene. You decide. "Clean care is safer care"].

PMID- 21195508
TI  - Acute cholecystitis and bacteraemia due to Streptococcus bovis biotype II.

PMID- 21195509
TI  - WITHDRAWN: Hemiconvulsion-hemiplegia-epilepsy syndrome: Follow-up of a case until
      adulthood.

PMID- 21195510
TI  - WITHDRAWN: Pharmacological parkinsonism vs. dementia with Lewy bodies.

PMID- 21195511
TI  - Subcortical reversible T2-weighed hypointensities in seizures secondary to
      diabetic ketoacidosis.

PMID- 21195512
TI  - Characterization of the baicalein-bovine serum albumin complex without or with
      Cu2+ or Fe3+ by spectroscopic approaches.
AB  - The binding of baicalein to bovine serum albumin (BSA) in the absence and
      presence of Cu2+ or Fe3+ in aqueous solution has been studied by fluorescence,
      synchronous fluorescence, ultraviolet-visible (UV-vis) spectra, circular
      dichroism (CD) and the three-dimensional (3D) fluorescence at pH 7.40. The
      decrease of the binding constant in the presence of Cu2+ or Fe3+ may result from
      the competition of the metal ions and baicalein binding to BSA. The effect of
      baicalein on the conformation of BSA was analyzed using UV, CD, fluorescence and
      three-dimensional (3D) fluorescence. These results indicate that the binding of
      baicalein to BSA causes apparent change in the secondary structure of BSA, but
      does not affect the polarity around the chromophore molecule.

PMID- 21195513
TI  - Estimating sediment and caesium-137 fluxes in the Ribble Estuary through time
      series airborne remote sensing.
AB  - High spatial and temporal resolution airborne imagery were acquired for the
      Ribble Estuary, North West England in 1997 and 2003, to assess the application of
      time-series airborne remote sensing to quantify total suspended sediment and
      radionuclide fluxes during a flood and ebb tide sequence. Concomitant
      measurements of suspended particulate matter (SPM) and water column turbidity
      were obtained during the time-series image acquisition for the flood and ebb tide
      sequence on the 17th July 2003 to verify the assumption of a vertically well
      mixed estuary and thus justifying the vertical extrapolation of spatially
      integrated estimate of surface SPM. The 137Cs activity concentrations were
      calculated from a relatively stable relationship between SPM and 137Cs for the
      Ribble Estuary. Total estuary wide budgets of sediment and 137Cs were obtained by
      combining the image-derived estimates of surface SPM and 137Cs with estimates of
      water volume from a two-dimensional hydrodynamic model (VERSE) developed for the
      Ribble Estuary. These indicate that around 10,000 tons of sediment and 2.72 GBq
      of 137Cs were deposited over the tidal sequence monitored in July 2003. This
      compared favourably with bed height elevation change estimated from field work.
      An uncertainty analysis on the total sediment and 137Cs flux yielded a total
      budget of the order of 40% on the final estimate. The results represent a novel
      approach to providing a spatially integrated estimate of the total net sediment
      and radionuclide flux in an intertidal environment over a flood and ebb tide
      sequence.

PMID- 21195514
TI  - Marked disequilibrium between 234Th and 230Th of the 238U natural radioactive
      decay chain in IAEA reference materials n. 312, 313 and 314.
AB  - A new laboratory for the spectroscopy of natural radioactivity with a good energy
      resolution is presented. It consists of two distinct parts equipped,
      respectively, the first one with a HpGe gamma-ray detector, whose setup has been
      already completed, and the second one with large area Silicon alpha-ray detectors
      and a radiochemical section for thin alpha-samples preparation, whose setup is
      yet in progress and will be the argument of a separate work. The gamma-ray
      spectrometer was calibrated by means of IAEA Reference Materials n. 312, 313, 314
      and 375. A large difference from the predictions of secular equilibrium emerged
      between the activities of (234)Th and (230)Th in Materials n. 312, 313 and 314.

PMID- 21195515
TI  - Aggressive growth and neoplastic potential of dentigerous cysts with particular
      reference to central mucoepidermoid carcinoma.
AB  - Epidermoid carcinoma and mucoepidermoid carcinoma that arise centrally within the
      jaws are often associated with dental cysts. Central mucoepidermoid carcinoma of
      the jaws is rare, and usually presents in the fourth to eighth decades; we know
      of only 7 cases that have been described in children younger than 16. Here we
      describe a central mucoepidermoid carcinoma in an 8-year-old girl that arose from
      a dentigerous cyst associated with an unerupted mandibular molar.

PMID- 21195516
TI  - Whole body, long-axis rotational training improves lower extremity neuromuscular
      control during single leg lateral drop landing and stabilization.
AB  - BACKGROUND: Poor neuromuscular control during sports activities is associated
      with non-contact lower extremity injuries. This study evaluated the efficacy of
      progressive resistance, whole body, long-axis rotational training to improve
      lower extremity neuromuscular control during a single leg lateral drop landing
      and stabilization. METHODS: Thirty-six healthy subjects were randomly assigned to
      either Training or Control groups. Electromyographic, ground reaction force, and
      kinematic data were collected from three pre-test, post-test trials. Independent
      sample t-tests with Bonferroni corrections for multiple comparisons were used to
      compare group mean change differences (P<=0.05/21<=0.0023). FINDINGS: Training
      group gluteus maximus and gluteus medius neuromuscular efficiency improved 35.7%
      and 31.7%, respectively. Training group composite vertical-anteroposterior
      mediolateral ground reaction force stabilization timing occurred 1.35s earlier.
      Training group knee flexion angle at landing increased by 3.5 degrees . Training
      group time period between the initial two peak frontal plane knee displacements
      following landing increased by 0.17s. Training group peak hip and knee flexion
      velocity were 21.2 degrees /s and 20.1 degrees /s slower, respectively. Time
      period between the initial two peak frontal plane knee displacements following
      landing and peak hip flexion velocity mean change differences displayed a strong
      relationship in the Training group (r(2)=0.77, P=0.0001) suggesting improved
      dynamic frontal plane knee control as peak hip flexion velocity decreased.
      INTERPRETATION: This study identified electromyographic, kinematic, and ground
      reaction force evidence that device training improved lower extremity
      neuromuscular control during single leg lateral drop landing and stabilization.
      Further studies with other populations are indicated.

PMID- 21195517
TI  - Impact of carbon nanomaterials on the behaviour of 14C-phenanthrene and 14C-benzo
      [a] pyrene in soil.
AB  - The impact of fullerene soot (FS), single-walled (SWCNTs) and multi-walled
      (MWCNTs) carbon nanotubes on the behaviour of two (14)C-PAHs in sterile soil was
      investigated. Different concentrations of carbon nanomaterials (0, 0.05, 0.1 and
      0.5%) were added to soil, and (14)C-phenanthrene and (14)C-benzo[a]pyrene
      extractability assessed over 80 d through dichloromethane (DCM) and hydroxypropyl
      beta-cyclodextrin (HPCD) shake extractions. Total (14)C-PAH activity in soils was
      determined by combustion, and mineralisation of (14)C-phenanthrene was monitored
      over 14 d, using a catabolically active pseudomonad inoculum. No significant loss
      of (14)C-PAH-associated activity from CNM-amended soils was observed over the
      'aging' period. CNMs had a significant impact on HPCD-extractability of (14)C
      PAHS; extractability decreased with increasing CNM concentration. Additionally,
      (14)C-phenanthrene mineralisation was inhibited by the presence of CNMs at
      concentrations of >= 0.05%. Differences in overall extents of (14)C
      mineralisation were also apparent between CNM types. It is suggested the addition
      of CNMs to soil can reduce PAH extractability and bioaccessibility, with PAH
      sorption to CNMs influenced by CNM type and concentration.

PMID- 21195518
TI  - Early nephrologist involvement in hospital-acquired acute kidney injury: a pilot
      study.
AB  - BACKGROUND: The optimal timing of nephrology consultation in patients with
      hospital-acquired acute kidney injury (AKI) is unknown. STUDY DESIGN: Prospective
      controlled nonrandomized intervention study. SETTING & PARTICIPANTS: We screened
      daily serum creatinine (SCr) levels of 4,296 patients admitted to the St. Louis
      Veterans Affairs Medical Center between September and November 2008 (control
      group) and January to May 2009 (intervention group). 354 patients (8.2%) met the
      definition of in-hospital AKI (SCr level increase of 0.3 mg/dL over 48 hours);
      176 of whom met all inclusion criteria; 85 and 91 patients were enrolled in the
      control (standard care) and intervention groups, respectively. INTERVENTION:
      Early renal service involvement (EARLI), defined as a 1-time nephrology
      consultation within 18 hours of the onset of AKI. OUTCOME: Primary outcome
      defined as 2.5-fold increase in SCr level from admission. MEASUREMENT: Daily SCr
      until discharge. RESULTS: The 2 groups had similar characteristics at baseline
      and at the time of AKI. The intervention was completed at a mean of 13.1 +/- 0.8
      hours from the onset of AKI. Nephrology recommendations in the EARLI group
      included specific diagnostic, therapeutic, and preventative components. The
      primary outcome occurred in 12.9% of patients in the control group compared with
      3.3% of patients in the EARLI group (P = 0.02). Patients in the EARLI group had a
      lower peak SCr level of 1.8 +/- 0.1 versus 2.1 +/- 0.2 mg/dL in controls (P =
      0.01). LIMITATIONS: Single-center nonrandomized study of mostly US male veterans.
      CONCLUSIONS: Early nephrologist involvement in patients with AKI may reduce the
      risk of a further decrease in kidney function. A larger randomized trial is
      needed to confirm the findings.

PMID- 21195519
TI  - Gender and the hygiene hypothesis.
AB  - The hygiene hypothesis offers an explanation for the correlation, well
      established in the industrialized nations of North and West, between increased
      hygiene and sanitation, and increased rates of asthma and allergies. Recent
      studies have added to the scope of the hypothesis, showing a link between
      decreased exposure to certain bacteria and parasitic worms, and increased rates
      of depression and intestinal auto-immune disorders, respectively. What remains
      less often discussed in the research on these links is that women have higher
      rates than men of asthma and allergies, as well as many auto-immune disorders,
      and also depression. The current paper introduces a feminist understanding of
      gender socialization to the epidemiological and immunological picture. That
      standards of cleanliness are generally higher for girls than boys, especially
      under the age of five when children are more likely to be under close adult
      supervision, is a robust phenomenon in industrialized nations, and some research
      points to a cross-cultural pattern. I conclude that, insofar as the hygiene
      hypothesis successfully identifies standards of hygiene and sanitation as
      mediators of immune health, then attention to the relevant patterns of gender
      socialization is important. The review also makes clear that adding a feminist
      analysis of gender socialization to the hygiene hypothesis helps explain
      variation in morbidity rates not addressed by other sources and responds to a
      number of outstanding puzzles in current research. Alternative explanations for
      the sex differences in the relevant morbidity rates are also discussed (e.g., the
      effects of estrogens). Finally, new sources of evidence for the hygiene
      hypothesis are suggested in the form of cross-cultural and other natural
      experiments.

PMID- 21195520
TI  - Liberating the NHS? A commentary on the Lansley White Paper, "Equity and
      Excellence".
AB  - In July 2010, the new Coalition Government unveiled its plans to make major
      changes to the English National Health Service (NHS). This paper, which provides
      a commentary on the NHS White Paper, Equity and Excellence: Liberating the NHS,
      casts doubt upon the extent to which the proposals will bring about the
      fundamental reform that the Government intends, not least because both the
      British public and GP commissioners (who are expected to play a central role in
      transforming the NHS) appear to have a limited appetite for radical market
      reform. The paper also identifies a number of unintended risks, including the
      large transitional costs and organisational turbulence resulting from further NHS
      reorganisation; and the fact that key aspects of the White Paper proposals could
      result in significant financial instability. Given the real world limitations to
      translating a rhetoric of localism and democratic legitimacy into reality and a
      lack of hard evidence about the benefits of market reform, the Government would
      be well advised to take a more cautious approach to health policy formulation and
      implementation and to ensure that any further changes to the NHS are based on
      evidence, piloting and evaluation.

PMID- 21195521
TI  - Factors in health initiative success: learning from Nepal's newborn survival
      initiative.
AB  - What shapes the level of political priority for alleviation of significant health
      problems in low-income countries? We investigate this question in the context of
      the significantly increasing political priority for newborn survival in Nepal
      since 2000. We use a process-tracing methodology to investigate causes of this
      shift, drawing on twenty-nine interviews with individuals close to newborn health
      policymaking in Nepal and extensive document analysis. Shifts in the political
      context (commitments to the child health MDG), the strength of concerned actors
      (emergence of collective action, leadership, resources) and the power of ideas
      (problem status, existence of contextually relevant solutions, agreement on these
      points) surrounding the issue have been instrumental in elevating priority for
      newborn survival, if not institutionalizing that priority to ensure long-term
      support. The findings highlight the significance of political fragmentation in
      war-torn areas for impeding priority generation. Additionally, theories of social
      construction provide important insights to the roles of ideas in shaping health
      initiative success.

PMID- 21195522
TI  - Stability of maxillary position after Le Fort I osteotomy using self-reinforced
      biodegradable poly-70L/30DL-lactide miniplates and screws.
AB  - PURPOSE: The purpose of this study was to evaluate the stability of Le Fort I
      osteotomy using self-reinforced biodegradable poly-70L/30DL-lactide miniplates
      and screws. PATIENTS AND METHODS: Nineteen patients who had Le Fort I osteotomy
      and internal fixation using self-reinforced biodegradable poly-70L/30DL-lactide
      miniplates and screws were evaluated both radiographically and clinically.
      Changes in maxillary position after operation were documented 1 week, 1, 3, 6 mo,
      and/or 1-yr postoperatively with lateral cephalometric tracings. Complications of
      the self-reinforced biodegradable poly-70L/30DL-lactide miniplates and screws
      were evaluated by follow-up roentgenograms and clinical observation. A mixed
      model analysis for repeated measures was used for statistical analysis. RESULTS:
      Maxillary position was stable after operation with no change between time points
      (P > .05). There were no complications with the self-reinforced biodegradable
      poly-70L/30DL-lactide miniplates and screws. CONCLUSIONS: Internal fixation of
      the maxilla after Le Fort I osteotomy with self-reinforced biodegradable poly
      70L/30DL-lactide miniplates and screws is a reliable method for maintaining the
      postoperative maxillary position after Le Fort I osteotomy.

PMID- 21195523
TI  - Analysis of maxillofacial injuries of vehicle passengers involved in frontal
      collisions.
AB  - PURPOSE: To clarify the incidence and mechanisms of maxillofacial injuries
      sustained by motor vehicle passengers, in-depth data from the Institute for
      Traffic Accident Research and Data Analysis, Japan, were retrospectively
      analyzed. MATERIALS AND METHODS: From the Institute for Traffic Accident Research
      and Data Analysis in-depth data for 1993 through 2005, data were collected for
      226 individuals with maxillofacial injuries who were adult passengers involved in
      frontal motor vehicle collisions. The accident information, a subject's medical
      data, and anatomic Injury Severity Scores were examined. RESULTS: The median
      Injury Severity Score was 2, and the mean equivalent barrier speed of the
      vehicles was 35.2 +/- 13.0 km/hour. The most common maxillofacial injuries were
      lacerations (46.7%), followed by abrasions (41.9%), fractures (14.0%), and dental
      injuries (5.7%). Maxillofacial fractures occurred more often in unrestrained
      drivers without airbag deployment (18.4%) and less often in restrained drivers
      with airbag deployment (4.3%). The incidences of fractures caused by impacts with
      areas other than the steering wheel were markedly decreased using any safety
      device (35.5% to 0%). CONCLUSION: Combined use of seat belts and airbags by
      occupants decreases fractures compared with completely unrestrained occupants.
      Furthermore, wearing a seat belt prevents the free flight of drivers within a
      vehicle and contact with the interior of a vehicle (other than the steering
      wheel). Although the anatomic Injury Severity Score of maxillofacial injuries was
      relatively low, because these injuries are also associated with socioeconomic
      costs, the correct use of safety devices and further development of more
      effective injury prevention systems are needed.

PMID- 21195524
TI  - Esthetic improvement using conventional orthodontic devices after segmental
      osteotomy in treatment of malpositioned implants.

PMID- 21195525
TI  - Changes in bone density and cyst volume after marsupialization of mandibular
      odontogenic keratocysts (keratocystic odontogenic tumors).
AB  - PURPOSE: To evaluate bone formation after marsupialization of odontogenic
      keratocysts (keratocystic odontogenic tumors) of the mandible. PATIENTS AND
      METHODS: A total of 53 patients with mandibular odontogenic keratocysts underwent
      marsupialization. Clinical and radiographic examinations were done at 1, 3, and 6
      months postoperatively. The bone density of the cyst site was measured on the
      panoramic radiographs using the Digora. The volume of the cyst was measured by
      injection of saline solution into the cyst cavity. Student t test and Spearman's
      rank correlation were used for statistical analysis. RESULTS: Healing was
      uneventful in all patients. The diameter of the cysts was 4.1 to 11.0 cm (average
      5.4). The panoramic radiographs showed a continuous increase in bone density of
      the cystic area, with a 22.42% increase at 1 month, 46.07% at 3 months, and
      64.69% at 6 months postoperatively compared with the preoperative values. The
      decrease in cyst volume was 19.05% at 1 month, 55.62% at 3 months, and 79.67% at
      6 months postoperatively. The increase in bone density and decrease in cyst
      volume were more significant in the first 3 months than in second 3 months (P <
      .01). The increase in bone density correlated inversely with the decrease in the
      cyst volume (P < .01). CONCLUSION: Bone regeneration can occur more rapidly in
      large mandibular odontogenic keratocysts after marsupialization with drainage by
      a cyst plug. After 3 months, secondary enucleation of the cyst can be performed.

PMID- 21195527
TI  - Using temporary anchorage devices to treat a pediatric mandible fracture.

PMID- 21195526
TI  - A suspected case of malignant hyperthermia after tooth extraction: case report.

PMID- 21195528
TI  - A simple surgical approach for management of the rhinoliths: case report.

PMID- 21195529
TI  - Odontogenic carcinosarcoma: case report and literature review.

PMID- 21195530
TI  - WITHDRAWN: Presurgical nasoalveolar molding with computer-aided reverse
      engineering and rapid prototyping technique in infants with unilateral cleft lip
      and palate.

PMID- 21195531
TI  - Blood loss in orthognathic surgery: a systematic review.
AB  - PURPOSE: Intraoperative blood loss during orthognathic surgery is frequently
      abundant and sometimes requires blood transfusion. The aim of the present study
      was to conduct a systematic review of the published data regarding intraoperative
      blood loss during orthognathic surgical interventions, including Le Fort I
      osteotomy, mandibular ramus osteotomy, and both combined, to determine the range
      of information available to help surgeons better prepare themselves, their
      patients, and the auxiliary support needed for this type of surgery and the
      transfusion requirements. MATERIALS AND METHODS: Selected reports from the PubMed
      and Cochrane Library databases for studies conducted from 1978 to 2008 were
      evaluated to determine whether they included information on the volume of
      bleeding during surgery and the factors that might have influenced the amount of
      bleeding. Of the 90 reports examined and evaluated, 7 were included in the
      critical analysis conducted as a part of the present systematic review. RESULTS:
      Referring to the reports used for statistical analysis of the volume of blood
      loss, the mean intraoperative bleeding volume was 436.11 mL, the mean of the
      standard deviations was +/-207.89 mL, and mean surgery duration was 196.9
      minutes. CONCLUSIONS: Our results have shown that the intraoperative bleeding
      observed in patients during Le Fort I or mandibular ramus osteotomies or both
      combined was less than the limits set for blood transfusion. However, bleeding
      was occasionally heavier, and surgeons should be prepared for heavier bleeding by
      reserving blood at a blood bank or by preparing an autotransfusion.

PMID- 21195532
TI  - Masseteric hypertrophy: considerations regarding treatment planning decisions and
      introduction of a novel surgical technique.

PMID- 21195533
TI  - Scanning electron microscopy analysis of luminal inflammation induced by
      different types of coronary stent in an animal model.
AB  - There is histological evidence that drug-eluting stents are associated with
      delayed endothelialization and a persistent inflammatory state. Moreover,
      clusters of inflammatory cells have been observed on luminal surfaces by scanning
      electron microscopy. With the aim of quantifying this inflammatory response, we
      implanted one bare-metal stent and two drug-eluting stents containing different
      doses of vinblastine embedded in the same polymer into the coronary arteries of
      12 domestic pigs. The density of inflammatory cells in a representative area (100
      x 100 MUm) was quantified at 3 and 7 days. Endothelialization was more complete
      in bare-metal stents than in drug-eluting stents at both 3 days (P=.016) and 7
      days (P=.0001). The degree of inflammation induced by the drug-eluting stents was
      higher than that induced by the bare-metal stents at both 3 days (11.8+/-3.5% vs.
      4.5+/-2%; P=.001) and 7 days (26.3+/-4.4% vs. 1.2+/-1.5%; P=.0001). In addition,
      the time sequence was inverted: the inflammatory response increased over time
      with the drug-eluting stents, while the opposite occurred with the bare-metal
      stents.

PMID- 21195534
TI  - Facilitating tracheal intubation using the Airtraq(r) laryngoscope during chest
      compression.

PMID- 21195535
TI  - Application of cupuassu shell as biosorbent for the removal of textile dyes from
      aqueous solution.
AB  - The cupuassu shell (Theobroma grandiflorum) which is a food residue was used in
      its natural form as biosorbent for the removal of C.I. Reactive Red 194 and C.I.
      Direct Blue 53 dyes from aqueous solutions. This biosorbent was characterized by
      infrared spectroscopy, scanning electron microscopy, and nitrogen
      adsorption/desorption curves. The effects of pH, biosorbent dosage and shaking
      time on biosorption capacities were studied. In acidic pH region (pH 2.0) the
      biosorption of the dyes were favorable. The contact time required to obtain the
      equilibrium was 8 and 18 h at 298 K, for Reactive Red 194 and Direct Blue 53,
      respectively. The Avrami fractionary-order kinetic model provided the best fit to
      experimental data compared with pseudo-first-order, pseudo-second-order and
      chemisorption kinetic adsorption models. The equilibrium data were fitted to
      Langmuir, Freundlich, Sips and Radke-Prausnitz isotherm models. For both dyes the
      equilibrium data were best fitted to the Sips isotherm model.

PMID- 21195536
TI  - Magnetic resonance imaging for the detection, localisation, and characterisation
      of prostate cancer: recommendations from a European consensus meeting.
AB  - BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) may have a role in
      detecting clinically significant prostate cancer in men with raised serum
      prostate-specific antigen levels. Variations in technique and the interpretation
      of images have contributed to inconsistency in its reported performance
      characteristics. OBJECTIVE: Our aim was to make recommendations on a standardised
      method for the conduct, interpretation, and reporting of prostate mpMRI for
      prostate cancer detection and localisation. DESIGN, SETTING, AND PARTICIPANTS: A
      consensus meeting of 16 European prostate cancer experts was held that followed
      the UCLA-RAND Appropriateness Method and facilitated by an independent chair.
      MEASUREMENT: Before the meeting, 520 items were scored for "appropriateness" by
      panel members, discussed face to face, and rescored. RESULTS AND LIMITATIONS:
      Agreement was reached in 67% of 260 items related to imaging sequence parameters.
      T2-weighted, dynamic contrast-enhanced, and diffusion-weighted MRI were the key
      sequences incorporated into the minimum requirements. Consensus was also reached
      on 54% of 260 items related to image interpretation and reporting, including
      features of malignancy on individual sequences. A 5-point scale was agreed on for
      communicating the probability of malignancy, with a minimum of 16 prostatic
      regions of interest, to include a pictorial representation of suspicious foci.
      Limitations relate to consensus methodology. Dominant personalities are known to
      affect the opinions of the group and were countered by a neutral chairperson.
      CONCLUSIONS: Consensus was reached on a number of areas related to the conduct,
      interpretation, and reporting of mpMRI for the detection, localisation, and
      characterisation of prostate cancer. Before optimal dissemination of this
      technology, these outcomes will require formal validation in prospective trials.

PMID- 21195537
TI  - Detection of tumor cells in the bone offers independent prognostic value in
      bladder cancer patients: the clinical and basic science perspective.

PMID- 21195538
TI  - Antimuscarinic treatment for overactive bladder symptoms: an all-time classic,
      yet still a clinical and basic challenge.

PMID- 21195539
TI  - Transplantation of autologous differentiated urothelium in an experimental model
      of composite cystoplasty.
AB  - BACKGROUND: Enterocystoplasty is associated with serious complications resulting
      from the chronic interaction between intestinal epithelium and urine. Composite
      cystoplasty is proposed as a means of overcoming these complications by
      substituting intestinal epithelium with tissue-engineered autologous urothelium.
      OBJECTIVE: To develop a robust surgical procedure for composite cystoplasty and
      to determine if outcome is improved by transplantation of a differentiated
      urothelium. DESIGN, SETTING, AND PARTICIPANTS: Bladder augmentation with in vitro
      generated autologous tissues was performed in 11 female Large-White hybrid pigs
      in a well-equipped biomedical centre with operating facilities. Participants were
      a team comprising scientists, urologists, a veterinary surgeon, and a
      histopathologist. MEASUREMENTS: Urothelium harvested by open biopsy was expanded
      in culture and used to develop sheets of nondifferentiated or differentiated
      urothelium. The sheets were transplanted onto a vascularised, de-epithelialised,
      seromuscular colonic segment at the time of bladder augmentation. After removal
      of catheters and balloon at two weeks, voiding behaviour was monitored and
      animals were sacrificed at 3 months for immunohistology. RESULTS AND LIMITATIONS:
      Eleven pigs underwent augmentation, but four were lost to complications. Voiding
      behaviour was normal in the remainder. At autopsy, reconstructed bladders were
      healthy, lined by confluent urothelium, and showed no fibrosis, mucus, calculi,
      or colonic regrowth. Urothelial morphology was transitional with variable
      columnar attributes consistent between native and augmented segments. Bladders
      reconstructed with differentiated cell sheets had fewer lymphocytes infiltrating
      the lamina propria, indicating more effective urinary barrier function.
      CONCLUSIONS: The study endorses the potential for composite cystoplasty by (1)
      successfully developing reliable techniques for transplanting urothelium onto a
      prepared, vascularised, smooth muscle segment and (2) creating a functional
      urothelium-lined augmentation to overcome the complications of conventional
      enterocystoplasty.

PMID- 21195541
TI  - Re: Beat Roth, Frederic D. Birkhauser, Pascal Zehnder, et al. Readaptation of the
      peritoneum following extended pelvic lymphadenectomy and cystectomy has a
      significant beneficial impact on early postoperative recovery and complications:
      results of a prospective randomized trial. Eur Urol 2011;59:204-10.

PMID- 21195540
TI  - The prognostic significance of capsular incision into tumor during radical
      prostatectomy.
AB  - BACKGROUND: The prognostic significance of capsular incision (CapI) into tumor
      during radical prostatectomy (RP) with otherwise organ-confined disease remains
      uncertain. OBJECTIVE: To evaluate the impact of CapI into tumor on oncologic
      outcome. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of 8110
      consecutive patients with prostate cancer treated at Ottawa Hospital and at
      Memorial Sloan-Kettering Cancer Center, both tertiary academic centers, between
      1985 and 2008. INTERVENTION: All patients underwent an open, laparoscopic or
      robotic RP. MEASUREMENTS: Patients were divided into four pathologic categories:
      group 1 (CapI group), positive surgical margins (PSMs) without extraprostatic
      extension (EPE); group 2, negative surgical margins (NSMs) without EPE; group 3,
      NSM with EPE; group 4, PSMs with EPE. Estimates of recurrence-free survival were
      generated with the Kaplan-Meier method. Recurrence was defined as a prostate
      specific antigen (PSA) >0.2 ng/ml and rising. Cox proportional hazards regression
      was used to estimate the hazard ratio (HR) for recurrence controlling for
      pretreatment PSA, RP date, RP Gleason sum, seminal vesicle invasion, and lymph
      node involvement. Pathologic categories were defined in the model by including
      the variables EPE and surgical margins (SMs) as well as their interaction.
      RESULTS AND LIMITATIONS: Median follow-up was 37.3 mo. The 5-yr recurrence-free
      probability after RP for the CapI group was 77% (95% confidence interval [CI], 72
      83). This was not only inferior to patients with NSMs and no EPE (log rank
      p<0.0001) but also to those with NSMs and EPE (log rank p=0.0002). In
      multivariate analysis the interaction between EPE and SM was not significant
      (p=0.26). In the adjusted model excluding the interaction term, patients with EPE
      had an increased risk for recurrence (HR: 1.80; 95% CI, 1.49-2.17; p<0.0001) as
      did those with positive margins (HR: 1.81; 95% CI, 1.51-2.15; p<0.0001). This was
      a retrospective study. CONCLUSIONS: CapI into tumor has a significant impact on
      patient outcome following RP. Patients, who otherwise would have organ-confined
      disease, will now have a higher probability of recurrence than those with
      completely resected extraprostatic disease.

PMID- 21195542
TI  - The expression of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (E-NPP1) is
      correlated with astrocytic tumor grade.
AB  - OBJECTIVE: Astrocytic brain tumors are subdivided in four grades. The most
      aggressive and invasive one is grade IV or glioblastoma multiforme (GBM). Ecto
      nucleotide pyrophosphatase/phosphodiesterase-1 (E-NPP1), a membrane-bound enzyme,
      is involved in many cellular processes such as modulation of purinergic
      signalling, nucleotide recycling, regulation of extracellular pyrophosphate
      levels and stimulation of cell motility. In this study, the use of anti-NPP1
      antibody in the determination of astrocytic tumor grade is evaluated. MATERIALS
      AND METHODS: Paraffin-embedded surgical specimens from 41 primary human
      astrocytic brain tumors (grade I=2; grade II=10; grade III=9; grade IV=20) and 5
      control samples are immunostained against NPP1 and glial fibrillary acid protein
      an astrocytic marker. RESULTS: In this communication, we report the expression of
      NPP1 in human astrocytic brain tumors. No expression could be detected in control
      tissue. We observed a remarkable up regulated expression of NPP1 in GBM. Taking
      the latter as 100%, grade I has a relative NPP1 staining of 7%, whereas grade II
      and III have a similar NPP1 expression level of 53% and 47% respectively.
      CONCLUSION: A correlation is found between the up-regulated expression of NPP1
      and the grade of the astrocytic tumor. Further investigation of NPP1 expression,
      especially in GBM, is necessary to determine the role of NPP1 in astrocytic brain
      tumor progression.

PMID- 21195543
TI  - Diosgenin induces death receptor-5 through activation of p38 pathway and promotes
      TRAIL-induced apoptosis in colon cancer cells.
AB  - Previously, we demonstrated that diosgenin induced apoptosis in colorectal cancer
      cell lines HCT-116 and HT-29. HT-29 cells have been reported to be one of the
      most resistant colorectal cancer cell lines to TRAIL-induced apoptosis. In this
      study, we investigated the effect of diosgenin on TRAIL-induced apoptosis in HT
      29 cells. We showed that diosgenin sensitizes HT-29 cells to TRAIL-induced
      apoptosis. Mechanisms underlying this sensitization mainly involved diosgenin
      induced p38 MAPK pathway activation and subsequent DR5 overexpression.
      Furthermore, we showed that diosgenin alone, TRAIL alone or combination treatment
      increased COX-2 expression and that the use of a COX-2 inhibitor further
      increased apoptosis induction.

PMID- 21195544
TI  - Construction of uniformly sized pseudo template imprinted polymers coupled with
      HPLC-UV for the selective extraction and determination of trace estrogens in
      chicken tissue samples.
AB  - To assess the potential risks associated with the environmental exposure of
      steroid estrogens, a novel highly efficient and selective estrogen enrichment
      procedure based on the use of molecularly imprinted polymer has been developed
      and evaluated. Herein, analogue of estrogens, namely 17-ethyl estradiol (EE(2))
      was used as the pseudo template, to avoid the leakage of a trace amount of the
      target analytes. The resulting pseudo molecularly imprinted polymers (PMIPs)
      showed large sorption capacity, high recognition ability and fast binding
      kinetics for estrogens. Moreover, using these imprinted particles as dispersive
      solid-phase extraction (DSPE) materials, the amounts of three estrogens (E(1),
      E(2) and E(3)) which were detected by HPLC-UV from the chicken tissue samples
      were 0.28, 0.31 and 0.17 MUg g(-1), and the recoveries were 72.5-78.7%, 90.3
      95.2% and 80.5-83.6% in spiked chicken tissue samples with RSD <7%, respectively.
      All these results reveal that EE(2)-PMIPs as DSPE materials coupled with HPLC-UV
      could be applied to the highly selective separation and sensitive determination
      of trace estrogens in chicken tissue samples.

PMID- 21195545
TI  - Adsorption of fluoride by waste iron oxide: the effects of solution pH, major
      coexisting anions, and adsorbent calcination temperature.
AB  - In this study, a waste iron oxide material (BT3), which is a by-product of the
      fluidized-bed Fenton reaction (FBR-Fenton), was thermally treated between 200 and
      900 degrees C and was used as an efficient adsorbent for the removal of fluoride
      ions in an aqueous system. The highest fluoride adsorption capacity occurred at
      the termination of the BT3 goethite dehydroxylation phase at about 300 degrees C
      calcination where both the volume of nanopores formed by dehydroxylation and the
      specific surface area reached their maximum values. Above 300 degrees C, BT3
      transformed to the hematite phase in which fluoride adsorption capacity decreased
      as calcination temperature increased. On the other hand, the effect of pH on the
      fluoride adsorption capacity of BT3 for various initial fluoride concentrations
      was examined. The optimum pH value was found to be about 4. After that efficiency
      decreased as pH became more alkaline. Finally, coexisting anions affected the
      fluoride adsorption capacity of BT3 at pH 3.9+/-0.2 in this order: PO(4)(3
      )>SO(4)(2-)>Cl(-)>NO(3)(-).

PMID- 21195546
TI  - Effectiveness and longevity of a green/food waste derived compost packed column
      to reduce Cr(VI) contamination in groundwater.
AB  - PAS100 accredited compost derived from green and food waste sources was used to
      remediate groundwater containing Cr(VI) at a historically contaminated site in
      Falkirk, Scotland, UK. The compost was mixed with gravel at a ratio of 1:1 (v/v)
      to provide a reactive bedding material in an upflow column. The Cr(VI)
      concentration in the groundwater (inlet) ranged from 0.5 to 7.8 mg L(-1) during
      the 168 d trial period. After an acclimation period of 54 d, the flow rate was
      increased in the column from 5.8 to 8 mL min(-1). Cr(VI) in the outlet was less
      than 100 MUg L(-1) up to 134 d, after which the concentration steadily increased
      till 168 d. Compost analysis following completion of the trial confirmed that
      Cr(VI) was captured within the column. Anaerobic microbial reduction of Cr(VI) to
      Cr(III) was thought to be a key mechanism responsible for the longevity of the
      system to remove Cr(VI) from the groundwater. Requiring no additional organic
      carbon or nitrogen during the trial period, this setup represents a cost
      effective treatment approach for low flow-through systems.

PMID- 21195547
TI  - Potential for biodegradation of polychlorinated biphenyls (PCBs) by Sinorhizobium
      meliloti.
AB  - Resting cell assay and soil microcosms were set up to investigate the
      biodegradation capability and metabolic intermediate of polychlorinated biphenyls
      (PCBs) by a rhizobial strain Sinorhizobium meliloti. Biodegradation was observed
      immediately after 2,4,4'-TCB was supplied as a sole source of carbon and energy
      in liquid cultures. After 6 days, the percent biodegradation of 2,4,4'-TCB was
      77.4% compared with the control. The main intermediate was identified as 2
      hydroxy-6-oxo-6-phenylhex-2,4-dienoic acid (HOPDA) for 2,4,4'-TCB as determined
      by gas chromatography-mass spectrometry (GC-MS). Inoculation with S. meliloti
      greatly enhanced the degradation of target PCB mixtures in the soil. Moreover,
      soil culturable bacteria, fungi and biphenyl degrading bacteria counts showed
      significant increase after inoculation of S. meliloti. This study suggests that
      S. meliloti is promising in PCB bioremediation.

PMID- 21195548
TI  - Fishpond sediment-borne DDTs and HCHs in the Pearl River Delta: characteristics,
      environmental risk and fate following the use of the sediment as plant growth
      media.
AB  - Investigation was made to characterize the fishpond sediment-borne DDTs and HCHs
      in a dyke-pond integrated agriculture-aquaculture system. Microcosm experiment
      was conducted to track the fate of DDTs and HCHs following the use of the
      sediment as plant growth media. The ratios of DDT/DDE+DDD, o,p'-DDT/p,p'-DDT and
      DDD/DDE were over 4, over 2 and nearly 2, respectively. These suggest that fresh
      DDT inputs from dicofol application are likely and anaerobic decomposition was
      the major pathway of DDT degradation. The sediments had higher percentage of
      delta-HCH and lower percentage of gamma-HCH, compared to technical HCH. The
      levels of both DDTs and HCHs were higher in the sediments, as compared to those
      in the estuarine sediments and fishpond sediments in non-traditional dyke-pond
      system. The sediment-borne DDTs and HCHs posed an environmental threat to the
      local ecosystem. Upon its use as plant growth media, the majority of DDTs was
      retained in the soil while <1/3 of the original soil-borne DDTs were lost; no
      leaching loss was recorded and plant uptake was negligible. Only <20% of the
      original soil-borne HCHs were retained in the soil while leaching loss accounted
      for 1.24%; nearly 79% of the original soil-borne HCHs disappeared as a result of
      HCHs degradation and possibly volatilization.

PMID- 21195549
TI  - Genomic loci and candidate genes underlying inflammatory nociception.
AB  - Heritable genetic factors contribute significantly to inflammatory nociception.
      To determine candidate genes underlying inflammatory nociception, the current
      study used a mouse model of abdominal inflammatory pain. BXD recombinant inbred
      (RI) mouse strains were administered the intraperitoneal acetic acid test, and
      genome-wide quantitative trait locus (QTL) mapping was performed on the mean
      number of abdominal contraction and extension movements in 3 distinct groups of
      BXD RI mouse strains in 2 separate experiments. Combined mapping results detected
      2 QTLs on chromosomes (Chr) 3 and 10 across experiments and groups of mice; an
      additional sex-specific QTL was detected on Chr 16. The results replicate
      previous findings of a significant QTL, Nociq2, on distal Chr 10 for formalin
      induced inflammatory nociception and will aid in identification of the underlying
      candidate genes. Comparisons of sensitivity to intraperitoneal acetic acid in BXD
      RI mouse strains with microarray mRNA transcript expression profiles in specific
      brain areas detected covarying expression of candidate genes that are also found
      in the detected QTL confidence intervals. The results indicate that common and
      distinct genetic mechanisms underlie heritable sensitivity to diverse
      inflammatory insults, and provide a discrete set of high-priority candidate genes
      to investigate further in rodents and human association studies. Novel genomic
      regions linked to inflammatory nociception were detected, a previously reported
      locus was confirmed, and high-priority candidate genes for inflammatory
      nociception and pain were identified.

PMID- 21195550
TI  - Use of crude, FML and rK39 antigens in ELISA to detect anti-Leishmania spp.
      antibodies in Felis catus.
AB  - Visceral leishmaniasis is a disease caused by Leishmania (Leishmania) chagasi and
      represents a serious public health problem. The dog is the main urban reservoir
      of the disease; however, investigations regarding the occurrence and
      epidemiological importance of leishmaniasis in cats have recently been initiated.
      This study aimed to detect cats seropositive for Leishmania spp. using different
      antigens. Additional studies were performed using sera from cats with Toxoplasma
      gondii (n=15) to evaluate cross-reactivity. Serum samples (n=113) from cats
      living in the town of Aracatuba, State of Sao Paulo, Brazil, an endemic area for
      human and canine visceral leishmaniasis, were tested by indirect ELISA using
      different antigens: crude (CAG-ELISA), fucose-mannose ligand (FML-ELISA) and K39
      (rK39-ELISA). Anti-Leishmania spp. antibodies were detected in 23.0% of samples
      evaluated by CAG-ELISA, 13.3% by FML-ELISA and 15.9% by RK39-ELISA. Only reactive
      sera in all three tests were considered truly positive. No disagreement occurred
      among the tests (p<0.05). Serum samples seropositive for toxoplasmosis tested by
      CAG-ELISA were negative, but one sample (6.7%) was positive for FML-ELISA and
      rK39-ELISA suggesting a cross-reaction between these antigens and anti-T. gondii
      antibodies. These findings indicate the occurrence of feline leishmaniasis in
      Aracatuba. Further studies are required to clarify the role of cats in the
      epidemiological cycle of leishmaniasis.

PMID- 21195551
TI  - Impact of bronchial circulation on bronchial exudates following combined burn and
      smoke inhalation injury in sheep.
AB  - We previously reported bronchial circulation contributes to pulmonary edema and
      increases shunt fraction following smoke inhalation, and bronchial blood flow
      significantly increases in inhalation injury. We hypothesized reduction of
      bronchial blood flow reduces exudation to the airway and ameliorates lung injury
      from combined burn and smoke insults (B&S injury). METHOD: Merino ewes (n=28)
      randomly divided into three groups: (1) bronchial artery ligated and injured
      (injury+ligation group); (2) bronchial artery left intact and injured (injury+no
      ligation group); (3) bronchial artery ligated but not injured (no injury+ligation
      group) were subjected to a flame burn and inhalation injury under halothane
      anesthesia. Parameters were analyzed using Scheffe's post hoc test (P<0.05). All
      Groups were resuscitated with Ringer lactate solution and placed on a ventilator
      for 48h. RESULTS: Pulmonary gas exchange (PaO(2)/FiO(2)) improved in
      injury+ligation group. Further, obstruction score, an index of airway cast
      formation, significantly changed between injury+no ligation group compared to
      both ligation groups. CONCLUSION: Bronchial circulation plays a significant role
      in lung injury after B&S injury, and reduction of bronchial blood flow by
      bronchial artery ligation reduces bronchial exudates, resulting in improved gas
      exchange.

PMID- 21195552
TI  - A decade of tyrosine kinase inhibitor therapy: Historical and current
      perspectives on targeted therapy for GIST.
AB  - The introduction of molecularly targeted therapies has ushered in a considerable
      transformation in the management of gastrointestinal stromal tumors (GIST) that
      currently defines the paradigm of targeted therapy for solid tumors. Indeed, in
      the past decade the management of GIST has evolved from a disease only
      effectively treatable by surgery to the archetype of a tumor treatable with a
      molecularly targeted therapy. Better understanding of the molecular and genetic
      characteristics that underlie the aberrant behavior of GIST has increased the
      accuracy of its diagnosis and allowed for the identification of distinct genetic
      hallmarks, prognostic groups, and treatment strategies. Collectively, this has
      resulted in the development of the targeted tyrosine kinase inhibitors (TKIs)
      imatinib and sunitinib, and continues to prompt studies of novel agents in this
      disease. Since approval in 2002, imatinib has been shown to provide a high level
      of clinical efficacy in patients with advanced GIST, including a median
      progression-free survival (PFS) of 2 years and median overall survival
      approaching 5 years, with some patients progression-free after 10 years of
      treatment. Imatinib is now also approved in adult patients following resection of
      KIT-positive GIST. In 2006, sunitinib was approved for the treatment of advanced
      GIST after failure of imatinib. Sunitinib provides significant benefit in this
      setting, with a median PFS close to 6 months after imatinib failure. Following
      progression on these agents, patients have limited treatment options. This
      critical unmet need is being addressed by the development of new TKIs and the use
      of novel regimens with approved agents.

PMID- 21195553
TI  - Stop smoking clinics in Malaysia: characteristics of attendees and predictors of
      success.
AB  - INTRODUCTION: As Stop Smoking Clinics (SSCs) become more common across the globe,
      it is important to know how far one can make broad generalisations concerning
      characteristics of smokers who attend these clinics and factors that predict
      their success. This involves accumulation of data from different countries.
      OBJECTIVE: The aim of this study was to identify characteristics of smokers and
      factors leading up to quitting with clinics in Malaysia. METHOD: Records from 629
      smokers who had sought help from five selected SSCs in Malaysia from January 2006
      to June 2007 were analysed. RESULTS: The characteristics of smokers attending
      Malaysian smoking clinics were broadly similar to those in Western countries.
      Consistent with the findings from other countries, older age and longest duration
      of previous quit attempts were associated with successful smoking cessation.
      Greater baseline carbon-monoxide readings (OR 0.96, 95% CI 0.93-0.99; p=0.013),
      but not Fagerstrom Test for Nicotine Dependence (FTND), predicted failure to quit
      at six-month in multivariate analysis. Success rates varied greatly between
      clinics even after adjusting for all other predictors. CONCLUSION: In these rare
      data from a non-Western culture some predictors of successful smoking cessation
      appeared to generalise from Western smokers but the universal validity of the
      FTND in particular needs to be examined further.

PMID- 21195554
TI  - Early adolescent cognitions as predictors of heavy alcohol use in high school.
AB  - The present study predicts heavy alcohol use across the high school years (aged
      14 through 18) from cognitions regarding the use of alcohol assessed in middle
      school. Using Latent Growth Modeling, we examined a structural model using data
      from 1011 participants in the Oregon Youth Substance Use Project. In this model,
      social images and descriptive norms regarding alcohol use in grade 7 were related
      to willingness and intention to drink alcohol in grade 8 and these variables were
      subsequently related to the intercept and slope of extent of heavy drinking
      across the high school years (grades 9 through 12). Across the sample, both
      descriptive norms and social images influenced the intercept of heavy drinking
      (in the 9th grade) through willingness to drink alcohol. Multiple sample analyses
      showed that social images also were directly related to the intercept of heavy
      drinking, for girls only. Results suggest that cognitions regarding alcohol use
      in middle school predict subsequent heavy drinking in high school. These findings
      emphasize the need for prevention programs targeting changing students' social
      images and encouraging a more accurate perception of peers' use when students are
      in middle school.

PMID- 21195555
TI  - A dual process account of adolescent and adult binge drinking.
AB  - This study adopted a dual process perspective to investigate the relative
      contributions of implicit and explicit cognitions to predicting binge drinking in
      adolescents and adults. Two hundred and seventy-two participants (136 teen-parent
      pairs) completed measures of alcohol memory associations (reflecting implicit
      cognition), expectancies about potential costs and benefits of alcohol use
      (reflecting explicit cognition), and self-reported binge drinking. Adolescents
      had stronger alcohol memory associations and perceived drinking benefits to be
      more probable than did adults. In turn, higher scores on the memory association
      and expected benefit measures were both associated with significantly higher
      levels of binge drinking. Moderation analyses revealed that alcohol memory
      associations and expected benefits of drinking were stronger predictors of binge
      drinking for adolescents than for adults. The findings suggest that both implicit
      and explicit cognitions may play important roles in alcohol use decisions, and
      these roles may differ for adolescents and adults.

PMID- 21195556
TI  - Characterizing binge drinking among U.S. military Veterans receiving a brief
      alcohol intervention.
AB  - BACKGROUND: Brief web-based alcohol interventions (BAIs) are effective for
      reducing binge drinking in college students and civilian adults, and are
      increasingly being applied to U.S. military populations. However, little is known
      about factors associated with binge drinking in Veteran populations and therefore
      some concern remains on the generalizability of studies supporting BAIs for
      addressing binge drinking in this population. This study sought to better
      understand the characteristics (e.g., demographic, coping related mental health
      factors, prior exposure to traumatic events, and factors assessing motivation to
      change alcohol use) of a predominantly male sample of binge drinking Veterans
      receiving a BAI from a VA provider. METHODS: A primarily male (93.5%) sample
      (N=554) of Veterans completed a BAI consisting of brief assessment and
      personalized feedback. RESULTS: We found that Veterans who were younger, used
      drugs/alcohol to cope with symptoms of PTSD and depression (e.g., nightmares and
      flashbacks and sleep difficulties), and had experienced sexual assault, had
      higher self-reported peak blood alcohol concentration and a higher likelihood for
      a binge drinking episode in the last 90days. CONCLUSIONS: BAIs may be a promising
      approach for addressing binge drinking in Veterans. However, binge drinking among
      a sample of mostly male Veterans receiving a BAI may be associated with a complex
      set of factors that are less prevalent in the college student population and thus
      studies demonstrating the efficacy of BAIs with Veterans are needed.

PMID- 21195557
TI  - A hypothetical relationship between the nuclear reprogramming factors for induced
      pluripotent stem (iPS) cells generation--bioinformatic and algorithmic approach.
AB  - A hypothetical evolutionary relationship was generated between the nuclear
      reprogramming factors for induced pluripotent stem (iPS) cells generation.
      Utilizing bioinformatics techniques, sequence analyses and phylogenetic tree
      algorithms, a comparative study has been performed to understand the evolutionary
      relationship of human nuclear reprogramming factors of induced pluripotent stem
      cells (iPSCs) generation. Among the total six nuclear reprogramming factors, the
      four reprogramming factors (SOX2, C-MYC, KLF4, and LIN28) have significant
      evolutionary origin. Our study shows SOX2 and C-MYC have evolutionary
      relationship and common point of origin. Likewise, KLF4 and LIN28 are having
      evolutionary relationship and have common point of origin. Based on these
      evidences, we propose that our study may be a great help to the future
      researchers to understand the mechanism(s) as well as pathway of nuclear
      reprogramming process.

PMID- 21195558
TI  - Relationship between the prenatal exposure to low-level of mercury and the size
      of a newborn's cerebellum.
AB  - Exposure to methylmercury at any stage of central nervous system development
      could induce alterations and result in severe congenital abnormalities. Total
      mercury level in maternal hair during pregnancy correlates well with blood levels
      of methylmercury and with total mercury levels in fetal brain. A prospective
      study has been conducted and a total of 137 childbearing women living at the
      coastal region with term, normal pregnancies were included and their newborns
      evaluated by ultrasonography. Mothers and their newborns are divided in two
      groups according to their hair mercury levels; examined group with high body
      levels of mercury (>= 1 MUg/g) and control group with low body levels of mercury
      (<1 MUg/g). Neurosonographic examination was conducted to all newborns. Two
      dimensions of cerebellum in the sagital-medial plane have been measured: maximum
      height and width starting from the roof of the fourth chamber. Majority of
      mothers had hair mercury levels lower than 1 MUg/g (N = 107). Mean value was 0.88
      MUg/g (SD 1.24), ranging from 0.02 to 8.71 MUg/g. There was no significant
      difference between the two groups when it comes to the width of cerebellum (Mann
      Whitney test: Z = 1471; p = 0.141). However, comparison related to the length of
      cerebellum shows statistically significant smaller cerebellum in newborns whose
      mother had hair mercury levels higher than 1 MUg/g (Mann-Whitney test: Z = 2329;
      p = 0.019). Our results lead to a conclusion that prenatal exposure to, what we
      consider to be, low-levels of methylmercury does influence fetal brain
      development detected as decreased size of newborn's cerebellum. From a clinical
      point of view, a question related to the influence of prenatal low-level
      methylmercury exposure on fetal neurodevelopment remains open. Our further
      objectives are to direct the research towards performing detailed
      neuropshychological tests on children at the age of 18 months. Such tests could
      indicate the presence of subtle neurological or neuropsychological deficits.

PMID- 21195559
TI  - The proposed mechanism of action during different pain management techniques on
      expression of cytolytic molecule perforin in patients after colorectal cancer
      surgery.
AB  - The postoperative period is accompanied with neuroendocrine, metabolic and immune
      alteration which is caused by tissue damage, anesthesia, postoperative pain and
      psychological stress. Postoperative pain contributes to dysfunction of immune
      response as a result of interaction between central nervous and immune system.
      The postoperatively activated hypotalamo-pituitary-adrenocortical axis, sympathic
      and parasympathic nerve systems are important modulators of immune response.
      According to bidirectional communication of immune and nervous system,
      appropriate postoperative pain management could affect immune response in
      postoperative period. Although the postoperative suppression of immune response
      has been reported, a very little are known about the influences of different pain
      management techniques on cytotoxic function of immune cells in patients with
      colorectal cancer in early postoperative period. Perforin is a cytotoxic molecule
      expressed by activated lymphocytes which has a crucial role in elimination of
      tumor cells and virus-infected cells, mostly during the effector's phase of
      immune response. Immune compromise during the postoperative period could affect
      the healing processes, incidence of postoperative infections and rate and size of
      tumor metastases disseminated during operation. The pharmacological management of
      postoperative pain in patients with malignancies uses very different analgesic
      techniques whose possible influence on cytotoxic functions of immune cells are
      still understood poor. For decades the most common way of treating postoperative
      pain after colorectal cancer surgery was intravenous analgesia with opiods. In
      the last decade many investigations pointed out that opiods can also contribute
      to postoperative suppression of immune response. Epidural analgesia is a regional
      anesthesia technique that acts directly on the origin of pain impulses and pain
      relief can be achieved with small doses of opiods combined with local
      anesthetics. Local anesthetics potentate analgesic properties of opiods but per
      se are also acting as antiinflammatory drugs. Afferent neural blockade by
      epidural analgesia attenuates neuroendocrine stress response. We propose that
      epidural analgesia could be more convenient that intravenous analgesia in
      maintenance of immunological homeostasis that is altered by surgical stress,
      tumor growth and pain.

PMID- 21195560
TI  - Effects of sodium lactate and acetic acid derivatives on the quality and sensory
      characteristics of hot-boned pork sausage patties.
AB  - Sodium lactate and acetic acid derivatives were evaluated for their effects on
      color retention, microbial growth, and sensory attributes of hot-boned pork
      sausage patties. Treatments included: (a) sodium lactate (L), (b) buffered
      vinegar (V), (c) sodium lactate and vinegar mixture (LV), (d) control with
      BHA/BHT (C), and (e) negative control (NC). Treatments L and LV decreased TPC at
      day 14 and day 16 when compared to control samples and reduced bacterial numbers
      up to 18 days. In addition, use of lactate and vinegar increased (P<0.05)
      acceptability and juiciness and reduced (P<0.05) off-flavor and rancidity when
      compared to control treatments at day 14. These results revealed that the L and
      LV sausage patties retained sensory acceptability and shelf-life quality from day
      14 through day 17 as opposed to other treatments. Additionally, sausage patties
      with LV maintained redness and sensory quality throughout 17 days of shelf-life,
      as compared to other treatments that retained color and quality for 14 days.

PMID- 21195561
TI  - Effects of dry-ageing on pork quality characteristics in different genotypes.
AB  - Presumably, dry-ageing enhances flavour attributes of meat by surface desiccation
      to increase and modify fatty acid content and other organoleptic molecules.
      However information regarding dry-ageing of fresh pork is limited. To examine the
      effects of dry-ageing on pork quality, Large White (LW, n = 24) and Large White *
      Duroc (Duroc, n = 24) barrows were slaughtered and three longissimus thoracis et
      lumborum sections from each side of the carcass were wet or dry-aged for 2, 7 or
      14 d. Dry-aged meat had lower (P < 0.001) moisture and higher (P < 0.001) protein
      content due to higher purge losses (P < 0.001) when compared with wet aged meat.
      However no dry-ageing effect (P > 0.05) was observed on sensory characteristics.
      The increase in the duration of ageing decreased moisture content and drip loss
      and increased (P < 0.001) protein content, purge loss and L*, chroma and hue
      values. These changes were more accentuated in dry-aged meat (P < 0.01). Days of
      ageing dependent increases (P < 0.001) were observed for instrumental and sensory
      tenderness and juiciness in both ageing types. Moreover, meat from Duroc barrows
      had lower (P < 0.001) moisture and protein content, and higher (P < 0.01) fat
      content, L* and hue values. Instrumental and sensory tenderness, juiciness and
      flavour were higher (P < 0.01) in meat from Duroc than LW barrows. Increases (P <
      0.01) in flavour intensity and decreases in off-flavour of meat from LW barrows
      were greater (P < 0.05) in d 7 than in d 14. Therefore the duration of ageing
      affected most quality and sensory characteristics, while the changes to quality
      attributes of dry versus wet-aged pork were attributable to the differences in
      shrink losses in the present study.

PMID- 21195562
TI  - End-to-side radial sensory to median nerve transfer to restore sensation and
      relieve pain in C5 and C6 nerve root avulsion.
AB  - PURPOSE: To report the results of end-to-side nerve transfer of the superficial
      radial nerve into the median nerve for restoration of sensation and pain relief
      at the dorsal radial aspect of the hand in C5 and C6 root avulsion. METHODS:
      Eight patients with a mean age of 32 years, with paresthesia and pain at the
      dorsal radial aspect of the hand due to upper brachial plexus injuries, had end
      to-side nerve transfer of the superficial radial nerve into the ulnovolar part of
      the median nerve. Five patients had S0 and 3 patients had S1 sensory evaluation
      at the dorsal radial aspect of the affected hand. We evaluated patients for pain
      using a visual analog scale. We assessed sensory recovery with the Semmes
      Weinstein monofilament test and British Medical Research Score, respectively. The
      follow-up period ranged from 24 to 36 months (average, 28 mo). RESULTS: Six
      patients had S2 and 2 patients had S3. All patients perceived at least one number
      lower of the Semmes-Weinstein filament in the dorsal radial aspect of the
      affected hand compared with the preoperative status. The best result was
      perception of the 3.61 filament in 2 patients. No downgrading of the donor nerve
      was observed after surgery. All patients had relief of pain 2 weeks after
      surgery, and the pain decreased dramatically at the last follow-up. CONCLUSIONS:
      This method is a reliable, effective, and simple procedure. We recommend this
      sensory nerve transfer as an additional procedure to the combined motor nerve
      transfers to relieve pain and restore sensation in the dorsal radial aspect of
      the hand in patients who have C5 and C6 root avulsion. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic IV.

PMID- 21195563
TI  - Quality of life and urinary incontinence in women.
AB  - Urinary incontinence greatly diminishes quality of life. It is important to
      diagnose the three main types of urinary incontinence correctly - stress, urge or
      mixed incontinence - and to evaluate the impact of incontinence on quality of
      life. After a detailed history, a bladder diary and questionnaires are the most
      useful tools with which to determine what aspects of quality of life are most
      impaired - daily, work-related, recreational or sexual activities. In general,
      urgency and urge incontinence have a worse effect on quality of life than stress
      urinary incontinence. Measures of quality of life have become essential in
      developing management plans and in follow-up.

PMID- 21195564
TI  - [Frequency of blood exposure accidents among medical students in Marrakech].

PMID- 21195565
TI  - [Bacterial flora in acute exacerbations of chronic obstructive pulmonary disease
      (COPD) in Kunming, China].
AB  - OBJECTIVE: Chinese recommendations for the management of acute exacerbations of
      chronic obstructive pulmonary disease (AECOPD) include antibiotic treatments
      targeting the most frequently isolated pathogens according to the severity of
      COPD. The study objective was to check the relevance of these recommendations in
      Yunnan, a Southern Chinese province. PATIENTS AND METHODS: A descriptive and
      analytical survey was conducted in the Kunming Medical University hospital among
      patients over 60 years of age, hospitalized with AECOPD, between March 2007 and
      June 2008. RESULTS: The 74 included patients were predominantly male (90%), with
      a mean age of 78.6 years, active or ex-smokers (81%), mainly with moderate (43%)
      or severe COPD (34%). Out of 87 AECOPD episodes, 47 (54%) yielded significant
      quantitative sputum cultures for S. pneumoniae (10%), P. aeruginosa (10%), H.
      influenzae (7%), M. catarrhalis (7%), and K. pneumoniae (7%). The positivity of
      sputum cultures was significantly linked with a history of smoking (P=0.002).
      More than half of the P. aeruginosa isolates were multidrug resistant.
      CONCLUSIONS: The distribution of pathogens isolated from EABPCO in Kunming
      corroborates published results. It does not question Chinese recommendations for
      first-line antibiotic therapy, but the high prevalence of P. aeruginosa and
      Enterobacteriaceae requires a periodic screening for acquired antibiotic
      resistance.

PMID- 21195566
TI  - [Hereditary complement deficiency in Tunisian adults with purulent meningitis].
AB  - Inherited complement deficiency is a rare disease. It predisposes to autoimmune
      diseases, glomerulonephritis, angioedema, and meningococcal meningitis. A
      prospective study was conducted over five years. The goal was to evaluate the
      prevalence of deficiency in Tunisian patients presenting with community acquired
      purulent meningitis and identify the type of deficiency. We enrolled 122
      patients, 15 of whom presented with a complement deficiency (12.3%). This
      prevalence was higher than the one observed in the global Tunisian population and
      in reported international data. The mean age of deficient patients (13 men and
      two women) was 24.7 years.

PMID- 21195567
TI  - [Evolution of Escherichia coli resistance in community acquired peritonitis].

PMID- 21195568
TI  - [Antimicrobial consumption reported through standardized reports on infection
      control activities, relationship with the ICATB public reporting indicator].
AB  - OBJECTIVE: The study's objective was to describe the evolution of antibiotic
      consumption between 2006 and 2008 in French health care facilities (HCF) its
      relations with the national policy of good antibiotics use using the ICATB score.
      METHOD: Data from standardized reports on infection control activities collected
      from 2006 to 2008 by the Ministry of Health (antibiotic consumptions and elements
      of antibiotic stewardship of every HCF) were analyzed with linear regression
      models to multilevel random intercept adjusted on HCF characteristics (public or
      private) and activity. RESULTS: The analysis was performed on 4062 (48,2%)
      observations after exclusion of HCF not concerned by the ICATB public reporting
      indicator (7.2% of observations), invalid or missing data (21,2% of observations)
      and irrelevant values (23.4%). The global antibiotic consumption was 343 defined
      daily doses (DDD) per 1000 patient-days (PD) and varied little between 2006 and
      2008. However, the linear regression model showed an increase of 5.7 DDD per 1000
      PDs per year (P<0.001). There was a positive association between antibiotic
      consumption and ICATB score, mainly concerning sub-scores ICATB-action and ICATB
      organization. CONCLUSION: The recent lack of decrease in antibiotic consumption
      in French HCF between 2006 and 2008 is coherent with other available national
      data, but exclusion of more than 50% of observations limits the impact of this
      analysis. The relationship between policy of good use and consumption of
      antibiotics remain difficult to specify, because of the short (three years) study
      length and because of the nature of ICATB, a composite indicator assessing only
      partly antibiotic policies.

PMID- 21195569
TI  - [Mediastinal pseudo-tumoral tuberculosis associated to systemic scleroderma].

PMID- 21195570
TI  - [Recurrent Corynebacterium striatum endocarditis, secondary to osteomyelitis].

PMID- 21195571
TI  - [Vaccination coverage of healthcare professionals in an infectious diseases
      department].
AB  - OBJECTIVES: The study's objective was to evaluate with a standardized
      questionnaire the knowledge of healthcare workers (HCWs) regarding occupational
      vaccinations and their vaccination coverage. POPULATION AND METHODS: This cross
      sectional survey was conducted in the department of infectious diseases of a 1796
      bed-teaching hospital in Dijon, France. RESULTS: Fifty-seven (93%) out of 61 HCPs
      completed the questionnaire. Vaccination against HVB was the most frequently
      mentioned vaccination (79%), followed by BCG (66%), and combine vaccine against
      diphtheria, tetanus, and polio (DTP) (66 %). Influenza was the most often quoted
      among recommended vaccinations (70%), followed by measles (61%), pertussis (39%),
      and varicella (14%). The number of correct answers was significantly correlated
      with age of participants, being a physician, and having had courses on
      vaccination. Almost all HCPs were up to date for mandatory vaccinations. In 2009
      to 2010, vaccination rates against seasonal flu and H1N1 flu reached 88%. Only
      52% of HCPs knew about their pertussis immunization and only a third of those
      born before 1980 had been tested for measles. CONCLUSIONS: HCPs knowledge of
      mandatory vaccinations is adequate but more limited for recommended vaccinations.
      Information on influenza vaccination has significantly improved its perception
      among HCPs resulting in a better adhesion to vaccination.

PMID- 21195572
TI  - Aortic and hepatic enhancement at multidetector CT: evaluation of optimal iodine
      dose determined by lean body weight.
AB  - PURPOSE: To determine the optimal iodine dose for aortic and hepatic enhancement
      at MDCT by comparing lean body weight (LBW) with total body weight (TBW).
      MATERIALS AND METHODS: This study was approved by our institutional review
      committee. One hundred and thirty-six patients were randomized into four groups:
      550, 650, 750 mg iodine/(kg of LBW) and 600 mgI/(kg of TBW). The aortic and
      hepatic contrast enhancements (Delta HUs) during the portal venous-phase and
      variances of DeltaHUs were compared. RESULTS: Mean DeltaHUs for 550, 650, 750
      mgI/kg LBW and 600 mgI/kg TBW were: 95.1, 109.9, 122.4, and 131.2HU,
      respectively, for the aorta. For the liver, 43.1, 55.4, 60.8, and 63.5 HU. Mean
      Delta HUs increased with iodine dose per kg LBW (p<0.01), but no significant
      difference between 750 mgI/kg LBW and 600 mgI/kg TBW groups. Hepatic enhancement
      increased by >=50 HU in 94% of patients with 750 mg/kg LBW. Variance of hepatic
      enhancement was marginally greater in the 600 mgI/kg TBW than in the 550 and 750
      mgI/kg LBW. CONCLUSION: Hepatic enhancement variation was reduced with iodine
      doses based on LBW. Iodine dose of 750 mg iodine/kg LBW was appropriate to
      achieve hepatic enhancement>=50 HU in 94% of patients.

PMID- 21195573
TI  - Large volume injection of 1-octanol as sample diluent in reversed phase liquid
      chromatography: application in bioanalysis for assaying of indapamide in whole
      blood.
AB  - Large volume injection of samples in strong diluents immiscible with the mobile
      phases used in reversed phase liquid chromatography (RPLC) has been recently
      introduced in practice. In the present work, the potential of the technique has
      been evaluated for bioanalytical applications. The process consists of the liquid
      liquid extraction of indapamide from whole blood into 1-octanol, followed by the
      direct injection from the organic layer into the LC. Detection was made through
      negative electrospray ionization (ESI) and tandem mass spectrometry (MS(2)). The
      method was developed, validated, and successfully applied to a large number of
      samples in two bioequivalence studies designed for indapamide 1.5mg sustained
      release and 2.5mg immediate release pharmaceutical formulations. The performance
      of the analytical method is discussed based on data resulting from the validation
      procedure and the completion of the bioequivalence studies.

PMID- 21195574
TI  - Sensitive and robust UPLC-MS/MS method to determine the gender-dependent
      pharmacokinetics in rats of emodin and its glucuronide.
AB  - In this study, a sensitive and robust ultraperformance liquid chromatography
      tandem mass spectrometry (UPLC-MS/MS) method was developed, validated, and
      applied to determine gender-dependent pharmacokinetics of total emodin
      (aglycone+glucuronide) in male and female Sprague-Dawley rats. The lower limit of
      quantification for emodin and emodin glucuronide in rat plasma was 39 and 78
      ng/ml, with signal-to-noise ratio of >= 10. Precision and accuracy studies showed
      emodin and emodin glucuronide plasma concentrations well within the 10% range in
      all studies. Plasma recovery of emodin and emodin glucuronide was always above
      86% for low (emodin: 39 ng/ml; glucuronide: 78 ng/ml), 92% for medium (625
      ng/ml), and 97% for high (10000 ng/ml) concentrations. Furthermore, emodin showed
      more than 95% plasma stability under short-term and long-term storage conditions,
      as well as after three freeze-thaw cycles in the experiments. The developed and
      validated analytical method was successfully applied to study the gender
      dependent 10-fold higher oral bioavailability of total emodin in male than female
      rats. The oral bioavailability of emodin and emodin glucuronide was also measured
      separately and showed a statistically significant gender difference in oral
      bioavailability of emodin and emodin glucuronide in rats.

PMID- 21195575
TI  - Effects of a cognitive behavioral self-help program on depressed mood for people
      with acquired chronic physical impairments: a pilot randomized controlled trial.
AB  - OBJECTIVE: Aim was to examine whether a new cognitive-behavioral self-help
      intervention program was effective in improving depressed mood in people with
      acquired chronic physical impairments. METHODS: Participants were 32 persons with
      acquired chronic physical impairments and depressive symptoms, who were randomly
      allocated to the Cognitive-Behavioral Self-help program (CBS) or the Waiting List
      Control group (WLC). Depression scores were assessed at three measurement
      moments: at pretest, immediately after completion of the intervention (posttest),
      and again two months later (follow-up). To evaluate changes in depression scores,
      Repeated Measures ANCOVA's were performed. RESULTS: It was shown that respondents
      who followed the CBS significantly improved compared to the WLC after completion
      of the program, and that this positive effect remained at 2-months follow-up.
      CONCLUSION: A cognitive-behavioral self-help intervention can be an effective
      tool to reduce depressive symptoms in people with physical impairments. PRACTICE
      IMPLICATIONS: A self-help program may prove to be more cost-effective for
      individuals and for the health care system as a whole. In addition, because a
      self-help intervention program can be delivered through mail or internet, a high
      number of people could be reached while overcoming geographical and social
      barriers to treatment.

PMID- 21195576
TI  - Sentinel lymph node biopsy in early breast cancer surgery--working with the risks
      of vital blue dye to reap the benefits.
AB  - AIMS: Sentinel lymph node biopsy (SLNB) is an important method of staging early
      breast cancer because of the inherent benefits it confers on patients in terms of
      arm function and quality of life. Its success depends on a high level of accuracy
      in detecting the sentinel node. This is achieved by a dual mapping technique that
      employs a radio-labelled nanocolloid and a vital blue dye. The vital dyes however
      carry the risk of anaphylaxis, and as more surgeons employ SLNB in their daily
      practice, a proportionate rise in the number of anaphylactic reactions can be
      expected. A comprehensive review of risks and benefits associated with using
      vital blues dyes has not been published and therefore a retrospective review was
      undertaken of the different levels of anaphylaxis associated with vital dyes as
      well as their benefits in SLNB. METHODS: An OVID MEDLINE search was performed of
      the English published literature using appropriate search terms to find published
      trial data and case series that focused on adverse reactions to vital blue dyes.
      RESULTS: The risk of severe anaphylaxis (grade 3) can be as low as 0.06%, and up
      to 0.4% for patients undergoing SLNB when data is analysed from large trials.
      Furthermore, adverse reactions associated with blue dyes are reversible with
      appropriate management. CONCLUSIONS: Surgeons should continue to use vital dyes
      to ensure that SLNB remains a highly sensitive procedure.

PMID- 21195577
TI  - Control chart methods for monitoring surgical performance: a case study from
      gastro-oesophageal surgery.
AB  - Graphical methods are becoming increasingly used to monitor adverse outcomes from
      surgical interventions. However, uptake of such methods has largely been in the
      area of cardiothoracic surgery or in transplants with relatively little impact
      made in surgical oncology. A number of the more commonly used graphical methods
      including the Cumulative Mortality plot, Variable Life-Adjusted Display,
      Cumulative Sum (CUSUM) and funnel plots will be described. Accounting for
      heterogeneity in case-mix will be discussed and how ignoring case-mix can have
      considerable consequences. All methods will be illustrated using data from the
      Scottish Audit of Gastro-Oesophageal Cancer services (SAGOCS) data set.

PMID- 21195578
TI  - Clinical study of transarterial chemoembolization combined with 3-dimensional
      conformal radiotherapy for hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers
      worldwide. Monotherapy is not very effective for intermediate or advanced stage
      HCC. Efficacy of combined therapy using transarterial chemoembolization (TACE)
      with three-dimensional conformal radiotherapy (3-DCRT) for advanced HCC should be
      evaluated. METHODS: HCC patients were selected from our patient database. The
      sequence of treatments that patients underwent was several courses of TACE
      followed in 2-4 weeks by 3-DCRT. The median tumor irradiation dose was 44Gy.
      Toxicity, tumor response, and overall survival rate were analyzed. RESULTS: 140
      HCC patients were followed up by the last follow-up time. Among these patients,
      hepatic toxicities due to treatment were notable in 15 cases. Gastrointestinal
      bleeding after the overall treatment occurred in 3 cases. Leukopenia of grade III
      was detected in 1 case. Radiation-induced liver disease (RILD) was observed in 3
      patients. Among 140 patients, 27, 97, and 16 cases achieved partial response,
      stable disease, and progressive disease, respectively. The overall survival rates
      of 1-year, 3-years, and 5-years were 66%, 29%, and 13%, respectively, with a
      median survival time of 18 months. Both Child-Pugh grade and radiation dose were
      determined to be independent predictors for overall survival from multivariate
      analysis. CONCLUSION: The combined modality of TACE and 3-DCRT is a promising
      treatment for unresectable HCC. A large-scale, prospective randomized trial
      should be performed to confirm the utility of this combined therapy.

PMID- 21195579
TI  - Objective preoperative measurement of anterior glenoid bone loss: a pilot study
      of a computer-based method using unilateral 3-dimensional computed tomography.
AB  - PURPOSE: The purpose of this study was to evaluate the reproducibility of
      unilateral computed tomography (CT) measurement of glenoid surface area, based on
      the typically circular geometry of the inferior glenoid. METHODS: This study used
      3-dimensional shoulder CT scans before reconstruction for anterior instability.
      The en face CT views of the normal and abnormal glenoids were randomized and
      evaluated by 3 independent observers (2 experienced shoulder surgeons and 1
      medical student). ImageJ (National Institutes of Health, Bethesda, MD) was used
      to overlay a perfect circle that was fit to the glenoid. The anterior aspect of
      the circle was then adjusted to match the true anatomic contour of the anterior
      glenoid. This adjusted region was used to determine the percentage of the perfect
      circle occupied by the glenoid, which we defined as the anatomic glenoid index
      (AGI). RESULTS: For the 23 normal shoulders, the AGI reflected a nearly perfect
      fit of the circle, with very high consistency and reliability among the 3
      observers. Overall, mean AGI for the normal shoulders was 100.5%, with an SD of
      2.2%. For the 12 shoulders that underwent Bankart repair, the overall AGI was
      92.1% +/- 5.2%, and 9 of 12 patients had an AGI below the threshold of 96.1%. For
      the 11 shoulders that underwent Latarjet reconstruction, the overall AGI was
      89.6% +/- 4.7%. CONCLUSIONS: This study confirms that the normal inferior glenoid
      surface is a nearly perfect circle with remarkably low variability. This
      observation allows for determination of a tight reference range that can be
      applied to clinical analysis of unilateral CT reconstructions of symptomatic
      shoulders. This pilot study evaluates a simple and reliable method for
      determination of the AGI, creating an anatomic preoperative description of bone
      loss. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PMID- 21195580
TI  - [Classification and etiology of acute aortic syndromes].
AB  - Acute aortic syndrome are significantly involved in "sudden death" and in
      hospital mortality remains high close to 30%, survivors are lifelong at risk for
      remaining aorta complication such as thoraco-abdominal aneurysm or new aorta
      dissection or aortic rupture. Classifications are useful tools to determine
      perioperative strategy. The Stanford system is determined by whether the
      ascending aorta is involved or not. In the Stanford Type A, the ascending aorta
      is involved, the treatment is surgical and urgent: type B, the ascending aorta is
      not involved, the treatment is a medical treatment: "anti-impulse therapy" based
      on the association of vasodilatator such as sodium nitroprusside and beta
      blockers such as atenolol. Endovascular therapy is the first-line therapy in case
      of visceral malperfusion. The De Backey system subdivides the dissection in three
      types, type 1: the intimal tear is in the ascending aorta and the dissection
      involves the entire aorta, type 2: the dissection is strictly limited to the
      ascending aorta, type 3: the dissection spares the ascending aorta and the arch.
      Principles for treatment are the same for type A and type 1 and 2, and for type B
      and type 3. High-risk patients (Marfan, bicuspid aortic valve, type IV Ehlers
      Danlos, history of dissection in family relatives) have to be closely followed by
      repeated radiologic and echocardiographic examination. Patient over 65 years old
      suffering from hypertension are mainly at risk and need a close control of their
      blood pressure. Whether conventional surgery and endovascular therapy have
      significantly improved, postoperative mortality remains high. Close medical
      follow up and prophylactic surgery may improve survival in high-risk population.

PMID- 21195581
TI  - Lung involvement in systemic sclerosis.
AB  - Scleroderma is a multisystem disease characterized by a severe inflammatory
      process and exuberant fibrosis. Lung involvement is a frequent complication and a
      leading cause of morbidity and mortality in this syndrome. Two major pulmonary
      syndromes are associated with scleroderma; a pulmonary vascular disorder evolving
      over time into relatively isolated pulmonary arterial hypertension (PAH), and
      interstitial lung disease (ILD). Each syndrome, when present, is a cause of
      morbidity and significantly reduces survival of scleroderma patients when
      compared to patients free of lung complication. When pulmonary hypertension and
      ILD are combined, survival is further reduced. Current therapy appears to have no
      meaningful effect on either condition and, thus, there is a need for better
      understanding of underlying pathogenic mechanisms. This review focuses on
      clinical, diagnostic, and therapeutic features of PAH and ILD as well as other
      frequent but less debilitating lung complications of scleroderma.

PMID- 21195582
TI  - Cross-validation of a modified score to predict mortality in cancer patients
      admitted to the intensive care unit.
AB  - PURPOSE: The aim of this study was to cross-validate an automated and customized
      severity of illness score as a means of predicting death among adult cancer
      patients admitted to the intensive care unit (ICU). MATERIALS AND METHODS: We
      conducted a retrospective study of ICU discharges between January 1, 2001, and
      December 31, 2005, in a university comprehensive cancer center. We randomly
      selected training and validation samples in 2 ICU groups (medical and surgical
      patients). We used logistic regression to calculate the probabilities of death in
      the ICU and in-hospital death in training samples and applied these probabilities
      to the validation samples to calculate sensitivity and specificity, construct
      curves, and determined the areas under the receiver operating characteristic
      curve (AUC). RESULTS: We included 6880 patients. In predicting ICU mortality, the
      AUC was 0.77 (95% confidence interval [CI], 0.73-0.82) for the medical validation
      group and 0.8207 (95% CI, 0.7304-0.9109) for the surgical validation group. For
      in-hospital mortality, the AUCs for the groups of medical and surgical patients
      were 0.73 (95% CI, 0.69-0.76) and 0.77 (95% CI, 0.73-0.80), respectively.
      CONCLUSIONS: The modified Sequential Organ Failure Assessment score is a good and
      valid predictor of cancer patients' risk of dying in the ICU and/or hospital
      despite the modifications needed to automate the score using existing electronic
      data.

PMID- 21195583
TI  - GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings
      tables.
AB  - This article is the first of a series providing guidance for use of the Grading
      of Recommendations Assessment, Development, and Evaluation (GRADE) system of
      rating quality of evidence and grading strength of recommendations in systematic
      reviews, health technology assessments (HTAs), and clinical practice guidelines
      addressing alternative management options. The GRADE process begins with asking
      an explicit question, including specification of all important outcomes. After
      the evidence is collected and summarized, GRADE provides explicit criteria for
      rating the quality of evidence that include study design, risk of bias,
      imprecision, inconsistency, indirectness, and magnitude of effect.
      Recommendations are characterized as strong or weak (alternative terms
      conditional or discretionary) according to the quality of the supporting evidence
      and the balance between desirable and undesirable consequences of the alternative
      management options. GRADE suggests summarizing evidence in succinct, transparent,
      and informative summary of findings tables that show the quality of evidence and
      the magnitude of relative and absolute effects for each important outcome and/or
      as evidence profiles that provide, in addition, detailed information about the
      reason for the quality of evidence rating. Subsequent articles in this series
      will address GRADE's approach to formulating questions, assessing quality of
      evidence, and developing recommendations.

PMID- 21195584
TI  - Revisiting stopping rules for iterative methods used in emission tomography.
AB  - The expectation maximization algorithm is commonly used to reconstruct images
      obtained from positron emission tomography sinograms. For images with acceptable
      signal to noise ratios, iterations are terminated prior to convergence. A new
      quantitative and reproducible stopping rule is designed and validated on
      simulations using a Monte-Carlo generated transition matrix with a Poisson noise
      distribution on the sinogram data. Iterations are terminated at the solution
      which yields the most probable estimate of the emission densities while matching
      the sinogram data. It is more computationally efficient and more accurate than
      the standard stopping rule based on the Pearson's chi(2) test.

PMID- 21195585
TI  - A critical review of interpositional grafts following temporomandibular joint
      discectomy with an overview of the dermis-fat graft.
AB  - The aim of this critical review is to determine what constitutes an ideal disc
      replacement material and whether any of the existing materials reported in the
      literature satisfy the requirements of an effective disc substitute following
      temporomandibular joint (TMJ) discectomy. Over the last half century a myriad of
      interpositional materials have been used in the TMJ but nearly all have been less
      than successful. The disasters that followed the early use of alloplastic
      interpositional implants in the 1980s prompted the increased use of autogenous
      grafts in the 1990s. Whilst studies by the author on the use of dermis-fat grafts
      have been largely positive, there are still concerns that make the dermis-fat
      graft a less than ideal interpositional material for use in discectomized joint
      cavities. In reviewing the literature, it is clear that there is still no ideal
      interpositional material that satisfies all the criteria for replacement of a
      missing articular disc following TMJ discectomy.

PMID- 21195586
TI  - Soft tissue changes during distraction osteogenesis.
AB  - This study aimed to investigate soft tissue changes in distraction osteogenesis
      depending on various distraction and consolidation periods. Fifteen male rabbits
      were divided into three groups and evaluated for five parameters. An external
      custom-made device was placed on the right side of the mandible. The
      postoperative latent period was 4 days. The groups were distracted for different
      periods (6 days, 3mm; 11 days, 5.5mm, 16 days, 8mm). For histomorphometric
      analyses, specimens were retrieved from both study and control sides of the
      mandible and were examined with light microscopy. The number of muscle fibres and
      nuclei on the study side increase proportionally with the distraction period.
      Regeneration in the first group continued in its natural pattern; in the second
      group, there seemed to be degeneration rather than regeneration; and in the third
      group there seemed to be a balance between regeneration and degeneration
      processes. In conclusion, when a massive amount of bone is to be obtained,
      instead of distracting the bone at once, it is thought to give better results if
      the total amount of distraction is divided into several time periods.

PMID- 21195587
TI  - Bilateral anterosuperior dislocation of intact mandibular condyles in the
      temporal fossa.
AB  - Dislocation of the temporomandibular joint occurs when the mandibular condyle is
      displaced anteriorly beyond the articular eminence and represents 3% of all
      dislocated joints reported in the body. Superolateral dislocation of the condyle
      into the temporal fossa is well documented in the literature, but anterosuperior
      dislocation without an associated fracture is rarely described. This report
      documents the case of a middle-aged woman with bilateral anterosuperior
      dislocation of the intact mandibular condyle after a fall on the face. This
      report reviews the literature on dislocations, suggests a nomenclature, possible
      causative mechanism and documents the importance of early management.

PMID- 21195588
TI  - Review of biomechanical models used in studying the biomechanics of reconstructed
      mandibles.
AB  - This study looked at computer and physical biomodels used to study the
      biomechanical performance of mandibular reconstruction, reviews the literature
      and explains the strengths and limitations of the models. Electronic databases
      (Pubmed, Medline) were searched. 17 articles were selected. Computer biomodels
      can be divided into virtual biomodels (mainly used for clinical diagnosis and
      treatment planning) and computational models (e.g. finite element analysis), they
      can predict areas most likely to fail based on internal stress distribution and
      areas of maximum stress concentration. Physical biomodels include: rapid
      prototyping, animal bone, human cadaveric bone, and bone substitute models.
      Physical models allow testing on a gross level to give fatigue performance and
      fracture strength. The use of bone substitutes allows a more consistent specimen
      size and a reduction in sample size. Some commercially available products can
      replicate the material properties of bone. The use of any biomodel depends on the
      question being asked: the bending strength of a reconstruction plate would
      necessitate a three point bending test; the biomechanical performance of a new
      method of reconstruction (e.g. the mandibular modular endoprosthesis) would
      necessitate finite element analysis to predict areas of likely failure and also a
      physical biomodel to look at fatigue failure.

PMID- 21195589
TI  - Application of systems biology approach identifies and validates GRB2 as a risk
      gene for schizophrenia in the Irish Case Control Study of Schizophrenia (ICCSS)
      sample.
AB  - Recently, we prioritized 160 schizophrenia candidate genes (SZGenes) by
      integrating multiple lines of evidence and subsequently identified twenty-four
      pathways in which these 160 genes are overrepresented. Among them, four
      neurotransmitter-related pathways were top ranked. In this study, we extended our
      previous pathway analysis by applying a systems biology approach to identifying
      candidate genes for schizophrenia. We constructed protein-protein interaction
      subnetworks for four neurotransmitter-related pathways and merged them to obtain
      a general neurotransmitter network, from which five candidate genes stood out. We
      tested the association of four genes (GRB2, HSPA5, YWHAG, and YWHAZ) in the Irish
      Case-Control Study of Schizophrenia (ICCSS) sample (1021 cases and 626 controls).
      Interestingly, six of the seven tested SNPs in GRB2 showed significant signal,
      two of which (rs7207618 and rs9912608) remained significant after permutation
      test or Bonferroni correction, suggesting that GRB2 might be a risk gene for
      schizophrenia in Irish population. To our knowledge, this is the first report of
      GRB2 being significantly associated with schizophrenia in a specific population.
      Our results suggest that the systems biology approach is promising for
      identification of candidate genes and understanding the etiology of complex
      diseases.

PMID- 21195590
TI  - Insulin receptor signaling in rat hippocampus: a study in STZ (ICV) induced
      memory deficit model.
AB  - Brain insulin receptors (IRs) have been suggested as an important regulatory
      factor for cognitive functions but the involvement of IR signaling in memory
      deficit associated with neurodegenerative conditions is not yet explored. In the
      present study, IR gene expression was studied by RT-PCR and signaling pathways by
      immunoblotting in CA1, DG and CA3 subregions of hippocampus in
      intracerebroventricular (ICV) administered streptozotocin (STZ, 3mg/kg twice)
      induced memory deficit model in rat. The effect of pre- and post-treatment of
      donepezil (5mg/kg po) and melatonin (20mg/kg po) on signaling pathways were
      studied. Effect of LY294002 (ICV), a PI3 Kinase inhibitor, was also investigated
      on memory functions and Akt phosphorylation. An increased IR expression (both
      gene and protein), phosphorylation of Shc, Erk1/2, IRS-1 and Akt in CA1 and CA3
      region of P2M fraction was observed after training as compared to control. STZ
      treated rats showed memory deficit and significant decrease in IR expression,
      phosphorylation of IRS-1 and Akt only in CA3 region as compared to trained group
      which were reversed by pre and post-treatment of melatonin but donepezil was
      effective only against memory deficit. LY294002 (3mM) treatment showed delayed
      learning and decrease in Akt phosphorylation. This study suggests that IR
      expression and its signaling pathways in hippocampal CA1 and CA3 regions are
      involved in memory functions and STZ (ICV) induced memory deficit. Hippocampal IR
      system might be playing an important role in regulation of memory functions,
      however only IR/IRS-1/Akt pathway in CA3 region is associated with STZ induced
      memory deficit.

PMID- 21195591
TI  - Selective adsorption of Mycobacterium Phlei on pyrite and sphalerite.
AB  - The adsorption of Mycobacterium Phlei cells on the surfaces of pyrite and
      sphalerite was studied as functions of time and pH. The results indicated that a
      higher amount of cells adsorbing onto pyrite compared with that onto sphalerite
      under neutral and alkaline conditions, and it was also observed from photographs
      of scanning electron micrograph. To gain a better insight into the mechanisms of
      differential adsorption, the functional groups on cell surfaces and the chemical
      states of each element on mineral surfaces before and after interaction with
      bacterial cells were investigated. The results showed that many groups presented
      on cells surface, such as C-O-H, C-O-C, C=O, C-N, N-H and P=O. The change in
      state of each element on pyrite and sphalerite surfaces after interaction with
      bacterial cells revealed that there were chemical reactions between metal ions
      and S on mineral surface and atoms like N, O, P, etc. on cell surface, and the
      shifts in binding energy of each element on pyrite surface is larger than that of
      sphalerite. Possible mechanisms for selective adsorption of bacterial cells onto
      pyrite and sphalerite were discussed in the latter part of this paper.

PMID- 21195592
TI  - Whole grain wheat sourdough bread does not affect plasminogen activator inhibitor
      1 in adults with normal or impaired carbohydrate metabolism.
AB  - BACKGROUND AND AIMS: Epidemiological studies suggest whole grain consumption is
      associated with a reduced risk of cardiovascular disease (CVD), possibly through
      alterations in glucose metabolism and subsequent effects on plasminogen activator
      inhibitor (PAI)-1, a novel biomarker for CVD. Our aim was to investigate the
      effect of 6 wk of whole grain wheat sourdough bread consumption versus refined
      white bread on PAI-1. METHODS AND RESULTS: Normoglycemic/normoinsulinemic (NGI; n
      = 14; age 53 +/- 6 y; BMI 26.5 +/- 2.9 kg/m(2)) and
      hyperglycemic/hyperinsulinemic (HGI; n = 14; age 57 +/- 7 y; BMI 35.7 +/- 5.7
      kg/m(2)) adults incorporated whole grain wheat sourdough (162.5 g) or white
      (168.8 g) bread into their diet, for 6 wk in a randomized crossover study. Pre-
      and post-intervention, fasting blood samples were analyzed for PAI-1 (primary
      outcome), as well as glucose, insulin and glucagon (secondary outcomes) at
      fasting and postprandially after an oral glucose tolerance test (OGTT).
      Anthropometric measures, fasting glucose, insulin, glucagon and PAI-1 antigen and
      activity were not different between treatments in either NGI or HGI adults.
      Glucose incremental area under the curve (iAUC) was lower (19%, P = 0.02) after 6
      wk consumption of whole grain wheat sourdough bread compared to white bread in
      the HGI group, with no differences in insulin or glucagon iAUC in either group.
      CONCLUSION: Our data showed decreased glucose iAUC after an OGTT following 6 wk
      whole grain wheat bread consumption in adults with differing glycemic/insulinemic
      status, but no improvements in PAI-1 or fasting glycemic parameters.

PMID- 21195593
TI  - Impact of metabolic syndrome on ischemic heart disease - a prospective cohort
      study in an Iranian adult population: Isfahan Cohort Study.
AB  - BACKGROUND: The impact of the metabolic syndrome among populations in the Middle
      East region is unknown; we therefore examined the association between the
      syndrome and the risk of ischemic heart disease (IHD) in an Iranian population.
      METHODS AND RESULTS: The Isfahan Cohort Study (ICS) prospectively followed 6146
      Iranian people (51.8% women, aged 35-75 years) from three cities and their rural
      districts who were initially free of ischemic heart disease. During the 5 year
      follow-up, 209 (56% men) cases of ischemic heart disease were detected. The
      metabolic syndrome was defined by the modified criteria of the National
      Cholesterol Education Program Adult Treatment Panel III (NCEP/ATPIII). End points
      were defined as fatal and nonfatal myocardial infarction, sudden cardiac death
      and unstable angina. A clear dose-response relationship was found between the
      number of metabolic risk factors and the incidence of IHD, with the hazard ratios
      increasing dose-dependently from 1.72 (95% CI 0.86-3.46) for only one to 1.97
      (1.00-3.90), 2.85 (1.45-5.58) and 4.44 (2.25-8.76) for 2, 3 and >=4 metabolic
      syndrome component respectively, relative to those with no component. The
      adjusted hazard ratio (95% CI) associated with the metabolic syndrome was 1.58
      (1.06-2.35) in men and 1.72 (1.08-2.74) in women for IHD. The contribution of
      metabolic syndrome to the IHD risk was particularly strong among smokers although
      there was no significant interaction. CONCLUSIONS: The metabolic syndrome by
      NCEP/ATPIII definition is a major determinant of ischemic heart disease in this
      middle-aged Iranian population, especially among smokers.

PMID- 21195594
TI  - Expression profiling of Ca(2+)/calmodulin-dependent signaling molecules in the
      rat dorsal and ventral hippocampus after acute lead exposure.
AB  - The septal and temporal poles of the hippocampus differ markedly in their
      anatomical organization, but whether these distinct regions exhibit differential
      neurochemical profiles underlying lead (Pb(2+)) neurotoxicity remains to be
      determined. In the present study, we examined changes in the expression of
      Ca(2+)/calmodulin-dependent enzymes, including calpain, calcineurin, phospho
      CaMKII (Thr286) and neuronal nitric oxide synthase (nNOS), in the rat dorsal and
      ventral hippocampus (DH and VH) after acute Pb(2+) exposure. Five days after
      Pb(2+) exposure, we observed constitutively active forms of calcineurin (45 kDa
      and 48 kDa) in ventral portions of the hippocampus, a result consistent with the
      observed calpain activation that is indicated by the breakdown of spectrin in
      this region. Our data demonstrate that nNOS expression is significantly higher in
      the ventral region of the hippocampus when compared to the dorsal region, whereas
      phosphorylation of CaMKII (Thr286) is less pronounced in the ventral portion of
      the hippocampus and more pronounced in dorsal regions after acute Pb(2+)
      exposure. Thus, it appears likely that the ventral region of hippocampus is more
      vulnerable to the neurotoxic effects of Pb(2+) than the dorsal region. Taken
      together, the present data suggest that acute lead exposure leads to differential
      expression patterns of Ca(2+)/calmodulin-dependent enzymes along the dorsoventral
      axis of the hippocampus.

PMID- 21195595
TI  - Pulmonary hypertension: an important predictor of outcomes in patients undergoing
      non-cardiac surgery.
AB  - OBJECTIVES: Perioperative risk associated with pulmonary hypertension (PH) in
      patients undergoing non-cardiac surgery (NCS) remains poorly defined. We report
      perioperative outcomes in a large cohort of patients undergoing NCS, comparing
      those with and without PH. METHODS: Patients undergoing NCS at our institution
      between January 2002 and December 2006, were cross matched with a Right Heart
      Catheterization (RHC) database for the same period. Patients were excluded if
      they were <18 years old and if they underwent cardiac surgery prior to NCS or
      minor procedures using local anesthesia or sedation. Controls were defined as
      patients who underwent similar NCS with mean pulmonary arterial pressure (MPAP)
      <= 25 mmHg. RESULTS: 173 patients underwent RHC and NCS during the specified
      period and were included in the analysis. Of these 96 (55%) had PH. Mean
      pulmonary arterial pressure (p = 0.001), American Association of Anesthesiology
      Class (p = 0.02), and chronic renal insufficiency (p = 0.03) were determined as
      independent risk factors for post-operative morbidity. Patients with PH were more
      likely to develop congestive heart failure (p < 0.001; OR: 11.9), hemodynamic
      instability (p < 0.002), sepsis (p < 0.0005), and respiratory failure (p <
      0.004). Patients with PH needed longer ventilatory support (p < 0.002), stayed
      longer in the ICU (p < 0.04), and were more frequently readmitted to the hospital
      within 30 days (p < 008; OR 2.4). CONCLUSIONS: In addition to the traditionally
      known risk factors for outcomes after NCS such as coronary artery disease,
      diabetes mellitus, chronic renal insufficiency, American Society of
      Anesthesiology class, the presence of underlying PH can have a significant
      negative impact on perioperative outcomes.

PMID- 21195596
TI  - Exergy analysis of the Chartherm process for energy valorization and material
      recuperation of chromated copper arsenate (CCA) treated wood waste.
AB  - The Chartherm process (Thermya, Bordeaux, France) is a thermochemical conversion
      process to treat chromated copper arsenate (CCA) impregnated wood waste. The
      process aims at maximum energy valorization and material recuperation by
      combining the principles of low-temperature slow pyrolysis and distillation in a
      smart way. The main objective of the exergy analysis presented in this paper is
      to find the critical points in the Chartherm process where it is necessary to
      apply some measures in order to reduce exergy consumption and to make energy use
      more economic and efficient. It is found that the process efficiency can be
      increased with 2.3-4.2% by using the heat lost by the reactor, implementing a
      combined heat and power (CHP) system, or recuperating the waste heat from the
      exhaust gases to preheat the product gas. Furthermore, a comparison between the
      exergetic performances of a 'chartherisation' reactor and an idealized
      gasification reactor shows that both reactors destroy about the same amount of
      exergy (i.e. 3500kWkg(wood)(-1)) during thermochemical conversion of CCA-treated
      wood. However, the Chartherm process possesses additional capabilities with
      respect to arsenic and tar treatment, as well as the extra benefit of
      recuperating materials.

PMID- 21195597
TI  - A novel immunochromatographic electrochemical biosensor for highly sensitive and
      selective detection of trichloropyridinol, a biomarker of exposure to
      chlorpyrifos.
AB  - We present a novel portable immunochromatographic electrochemical biosensor (IEB)
      for simple, rapid, and sensitive biomonitoring of trichloropyridinol (TCP), a
      metabolite biomarker of exposure to organophosphorus insecticides. Our new
      approach takes the advantage of immunochromatographic test strip for a rapid
      competitive immunoreaction and a disposable screen-printed carbon electrode for a
      rapid and sensitive electrochemical analysis of captured HRP labeling. Several
      key experimental parameters (e.g. immunoreaction time, the amount of HRP labeled
      TCP, concentration of the substrate for electrochemical measurements, and the
      blocking agents for the nitrocellulose membrane) were optimized to achieve a high
      sensitivity, selectivity and stability. Under optimal conditions, the IEB has
      demonstrated a wide linear range (0.1-100 ng/ml) with a detection limit as low as
      0.1 ng/ml TCP. Furthermore, the IEB has been successfully applied for
      biomonitoring of TCP in the rat plasma samples with in vivo exposure to
      organophosphorus insecticides like Chlorpyrifos-oxon (CPF-oxon). The IEB thus
      opens up new pathways for designing a simple, rapid, clinically accurate, and
      quantitative tool for TCP detection, as well as holds a great promise for in
      field screening of metabolite biomarkers, e.g., TCP, for humans exposed to
      organophosphorus insecticides.

PMID- 21195598
TI  - Styryl-BODIPY based red-emitting fluorescent OFF-ON molecular probe for specific
      detection of cysteine.
AB  - We have synthesized a styryl boron-dipyrromethene (BODIPY)/2,4
      dinitrobenzenesulfonyl (DNBS) dyad based red-emitting molecular probe for
      specific detection of cysteine among the biological thiols. The probe shows
      intensive absorption at 556 nm and the probe is non-fluorescent. The DNBS moiety
      can be cleaved off by thiols, the red emission of the BODIPY fluorophore at 590
      nm is switched on, with an emission enhancement of 46-fold. The probe shows good
      specificity toward cysteine over other biological molecules, such as glutathione
      and amino acids. The emission of the probe is pH-independent in the physiological
      pH range. The probe is used for fluorescent imaging of cellular thiols.
      Theoretical calculations based on density functional theory (DFT) were used to
      elucidate the fluorescence sensing mechanism of the probe, which indicate a dark
      excited state (S(1)) for the probe but an emissive excited state (S(1)) for the
      cleaved product (i.e. the fluorophore).

PMID- 21195599
TI  - A reagentless, disposable and multiplexed electronic biosensing platform:
      application to molecular logic gates.
AB  - The construction of a reagentless, sensitive, disposable and multiplexed
      electronic sensing platform for one-spot simultaneous determination of
      biomolecules with significant difference in size (proteins and small molecules)
      is described. The sensing surface is fabricated by the hybridization of two types
      of redox-tags conjugated aptamers with the corresponding complementary DNAs,
      which are self-assembled on a gold nanoparticle-modified screen printed carbon
      electrode. The presence of the target analytes leads to the release of the tagged
      signaling aptamers from the sensing surface, and the surface-remained tags
      exhibit well-resolved peaks, whose positions and sizes reflect the identities and
      concentrations of the target analytes, respectively. The application of the
      proposed sensing platform for molecular logic gate operations is also
      demonstrated.

PMID- 21195600
TI  - Strategically functionalized carbon nanotubes as the ultrasensitive
      electrochemical probe for picomolar detection of sildenafil citrate (Viagra).
AB  - The present work demonstrates the utility of the functionalized carbon nanotubes,
      poly(4-aminobenzene sulfonic acid) (PABS) grafted multiwalled carbon nanotubes,
      MWNT-g-PABS, as an electrode modifier towards achieving ultrasensitive detection
      of a model drug, sildenafil citrate (SC). PABS units in MWNT-g-PABS interact with
      SC, pre-concentrate and accumulate at the surface. The electron transduction from
      SC to electrode is augmented via MWNT-g-PABS. As a result, the MWNT-g-PABS
      modified electrode exhibited ultrasensitive (57.7 MUA/nM) and selective detection
      of SC with a detection limit of 4.7 pM. The present work provides scope towards
      targeting ultrasensitivity for the detection of biomolecules/drug through
      rational design and incorporation of appropriate chemical components to carbon
      nanotubes.

PMID- 21195601
TI  - Sensitive electrochemical immunosensor for cancer biomarker with signal
      enhancement based on nitrodopamine-functionalized iron oxide nanoparticles.
AB  - A novel electrochemical immunosensor for sensitive detection of cancer biomarker
      prostate specific antigen (PSA) based on nitrodopamine (NDA) functionalized iron
      oxide nanoparticles (NDA-Fe(3)O(4)) is described. NDA-Fe(3)O(4) was used both for
      the immobilization of primary anti-PSA antibody (Ab(1)) and as secondary anti-PSA
      antibody (Ab(2)) label. For the preparation of the label, mediator thionine (TH)
      was first conjugated onto NDA-Fe(3)O(4) based on the amino groups of NDA, and
      then the amino group of TH was used to immobilize horseradish peroxidase (HRP)
      and Ab(2). Due to the high amount of NDA anchored onto Fe(3)O(4) surface, the
      loading of antibodies as well as mediator and enzyme onto NDA-Fe(3)O(4) was
      substantially increased, which increased the sensitivity of the immunosensor. The
      resulting immunosensor displayed a wide range of linear response (0.005-50
      ng/mL), low detection limit (4 pg/mL), good reproducibility and stability. The
      immunosensor was used to detect the PSA contents in serum samples with
      satisfactory results.

PMID- 21195602
TI  - Covalent immobilization of cholesterol oxidase on self-assembled gold
      nanoparticles for highly sensitive amperometric detection of cholesterol in real
      samples.
AB  - A novel scheme for the fabrication of gold nanoparticle modified cholesterol
      oxidase based bioelectrode is presented and its application potential for
      cholesterol biosensor is investigated. The fabrication procedure is based on the
      deposition of gold nanoparticles on the 1,6-hexanedithiol modified gold
      electrode, functionalization of the surface of deposited gold nanoparticles with
      carboxyl groups using 11-mercaptoundecanoic acid and then covalent immobilization
      of cholesterol oxidase on the surface of gold nanoparticle film using the N-ethyl
      N'-(3-dimethylaminopropyl carbodimide) and N-hydroxysuccinimide ligand chemistry.
      The assembly process of the bioelectrode is investigated using atomic force
      microscopy, cyclic voltammetry and electrochemical impedance spectroscopy. The
      gold nanoparticle film on the electrode surface provided an environment for the
      enhanced electrocatalytic activities and thus resulted in enhanced analytical
      response. The resulting bioelectrode is further applied to the amperometric
      detection of cholesterol and exhibited a linear response to cholesterol in the
      range of 0.04-0.22 mM with a detection limit of 34.6 MUM, apparent Michaelis
      Menten constant (K(m)(app)) of 0.062 mM and a high sensitivity of 9.02 MUA mM(
      1). The fabricated bioelectrode is successfully used for the selective
      determination of cholesterol in human serum samples.

PMID- 21195603
TI  - Chemical and biological characterisation of a sensor surface for bioprocess
      monitoring.
AB  - This paper describes the step-wise fabrication and characterisation of a multi
      layer dual polarization interferometry (DPI) based biosensor utilising Protein G
      (ProG) as the bio-recognition layer for the detection of a fragment antibody
      (Fab'). The biosensor is capable of monitoring the concentration of Fab' product
      within the extracellular medium of a fed-batch fermentation after leakage from
      Escherichia coli (E.coli). The activity, stability and functionality of each
      sensor layer were analysed in situ using DPI, whilst the chemical identity and
      homogeneity of the chemical layers were assessed ex situ using X-ray
      photoelectron spectroscopy (XPS) and secondary ion mass spectrometry (SIMS). Two
      different biotin linkers were found to produce hugely differing surfaces after
      the capture of NeutrAvidinTM (NA) and biotinylated Protein G (b-ProG). The
      hydrophilic (PEG)(4)-biotin linker resulted in a surface where the b-ProG layer
      was deposited and organised above the NA layer producing an active and stable
      surface, whilst the hydrophobic LC-biotin linker generated a surface where the b
      ProG layer was buried within the NA layer leading to variable surfaces and poor
      binding of the Fab' target. The biosensor has a detection limit of 1.7 MUg/ml
      with a dynamic range covering two orders of magnitude. The sensor can detect the
      onset of Fab' leakage as early as 2h following product induction, with high
      signal-to-noise ratios and little interference from extracellular components.
      Leakage of Fab' followed a biphasic profile, switching to a more rapid rate 20 h
      after induction, indicating accelerated product loss and the need for cultivation
      harvest.

PMID- 21195604
TI  - First evidence for digenic inheritance in hereditary colorectal cancer by
      mutations in the base excision repair genes.
AB  - Biallelic mutations in the base excision repair gene Mut Y homologue (MUTYH) are
      responsible for variable recessively inherited phenotypes of polyposis. Beside
      MUTYH, the proteins 8-oxo-guanine DNA glycosylase (OGG1) and MTH1 (or NUDT1) are
      also involved in the repair of 7,8-dihydro-8-oxoguanine (8-oxo-G), previous
      studies, however, only found missense mutations of unclear pathogenicity in
      either MTH1 or OGG1. To investigate the role of a defective 8-oxo-G repair we
      performed a germline mutation screening in the genes OGG1, MTH1 and MUTYH, in 81
      patients with a clinical phenotype ranging from attenuated or atypical
      adenomatous polyposis coli including hyperplastic polyps to hereditary non
      polyposis colorectal cancer (HNPCC) type X syndrome without mono- or biallelic
      mutations in either APC, MUTYH or the DNA mismatch repair genes. We describe here
      the first pathogenic germline mutation in OGG1, a splice site mutation affecting
      exon 1, which was inherited from the father, in combination with a maternal MUTYH
      missense mutation p.Ile223Val in a female patient with advanced synchronous colon
      cancer and adenomas at the age of 36 years pointing towards digenic inheritance
      for colorectal cancer (CRC) predisposition. Monoallelic missense mutations in
      MTH1 (3x), OGG1 (2x), or MUTYH (3x) were identified in 10 patients (12%), three
      of them were novel. Our findings indicate that mutations in other genes of the 8
      oxo-G repair beside MUTYH are involved in CRC predisposition. Oligogenic
      inheritance affecting genes of a certain repair pathway might therefore be the
      missing link between monogenic and polygenic traits.

PMID- 21195605
TI  - Preoperative MRI and surgical management in patients with nonpalpable breast
      cancer: the MONET - randomised controlled trial.
AB  - BACKGROUND: We evaluated whether performing contrast-enhanced breast MRI in
      addition to mammography and/or ultrasound in patients with nonpalpable suspicious
      breast lesions improves breast cancer management. METHODS: The MONET - study (MR
      mammography of nonpalpable breast tumours) is a randomised controlled trial in
      patients with a nonpalpable BIRADS 3-5 lesion. Patients were randomly assigned to
      receive routine medical care, including mammography, ultrasound and lesion
      sampling by large core needle biopsy or additional MRI preceding biopsy. Patients
      with cancer were referred for surgery. Primary end-point was the rate of
      additional surgical procedures (re-excisions and conversion to mastectomy) in
      patients with a nonpalpable breast cancer. FINDINGS: Four hundred and eighteen
      patients were randomised, 207 patients were allocated to MRI, and 211 patients to
      the control group. In the MRI group 74 patients had 83 malignant lesions,
      compared to 75 patients with 80 malignant lesions in the control group. The
      primary breast conserving surgery (BCS) rate was similar in both groups; 68% in
      the MRI group versus 66% in the control group. The number of re-excisions
      performed because of positive resection margins after primary BCS was increased
      in the MRI group; 18/53 (34%) patients in the MRI group versus 6/50 (12%) in the
      control group (p=0.008). The number of conversions to mastectomy did not differ
      significantly between groups. Overall, the rate of an additional surgical
      intervention (BCS and mastectomy combined) after initial breast conserving
      surgery was 24/53 (45%) in the MRI group versus 14/50 (28%) in the control group
      (p=0.069). INTERPRETATION: Addition of MRI to routine clinical care in patients
      with nonpalpable breast cancer was paradoxically associated with an increased re
      excision rate. Breast MRI should not be used routinely for preoperative work-up
      of patients with nonpalpable breast cancer.

PMID- 21195606
TI  - Optimization of food waste hydrolysis in leach bed coupled with methanogenic
      reactor: effect of pH and bulking agent.
AB  - The effects of pH and bulking agents on hydrolysis/acidogenesis of food waste
      were studied using leach bed reactor (LBR) coupled with methanogenic up-flow
      anaerobic sludge blanket (UASB) reactor. The hydrolysis rate under regulated pH
      (6.0) was studied and compared with unregulated one during initial experiment.
      Then, the efficacies of five different bulking agents, i.e. plastic full
      particles, plastic hollow sphere, bottom ash, wood chip and saw dust were
      experimented under the regulated pH condition. Leachate recirculation with 50%
      water replacement was practiced throughout the experiment. Results proved that
      the daily leachate recirculation with pH control (6.0) accelerated the hydrolysis
      rate (59% higher volatile fatty acids) and methane production (up to 88%)
      compared to that of control without pH control. Furthermore, bottom ash improved
      the reactor alkalinity, which internally buffered the system that improved the
      methane production rate (0.182 l CH(4)/g VS(added)) than other bulking agents.

PMID- 21195607
TI  - Combined thermochemical and fermentative destruction of municipal biosolids: a
      comparison between thermal hydrolysis and wet oxidative pre-treatment.
AB  - In this study the comparative destruction of municipal biosolids using thermal
      hydrolysis (140 or 165 degrees C) and wet oxidation (220 degrees C) was followed
      by biological degradation via mesophilic anaerobic digestion (36 degrees C). Wet
      oxidation (WO) destroyed more than 93% of the VSS, while thermal hydrolysis (TH)
      at 140 and 165 degrees C destroyed 9% and 22%, respectively. Combined TH and
      anaerobic digestion resulted in approximately 50% VSS destruction. The ultimate
      methane potential of the combined fractions from the thermal hydrolysis at 140
      and 165 degrees C improved by 12-13% relative to the untreated control sample.
      Methane production from the WO material was 53% of the control yield and wholly
      attributable to soluble organic carbon in the liquid fraction, indicating that
      the WO destroyed all putrescible carbon from the solids fraction. Point sampling
      during the BMP assay revealed that methanogenic development, not solids
      hydrolysis, was the kinetic barrier during anaerobic digestion in this study.

PMID- 21195608
TI  - Accumulation of lead by free and immobilized cyanobacteria with special reference
      to accumulation factor and recovery.
AB  - Lead accumulation by free and immobilized cyanobacteria, Lyngbya majuscula and
      Spirulina subsalsa was studied. Exponentially growing biomass was exposed to 1
      20mg L(-1) of Pb(II) solution at pH 6, 7 and 8 for time periods ranging from 10
      min to 48 h. L. majuscula accumulated 10 times more Pb (13.5 mg g(-1)) than S.
      subsalsa (1.32 mg g(-1)) at pH 6 within 3h of exposure to 20mg L(-1) Pb(II)
      solution and 76% of the Pb could be recovered using 0.1M EDTA. This chelator (2
      MUM) did not influence Pb accumulation whereas 100 MUM citrate increased that of
      S. subsalsa 6- to 8-fold. L. majuscula filaments enmeshed in a glass wool packed
      in a column removed 95.8% of the Pb from a 5mg L(-1) Pb solution compared to free
      and dead biomass which removed 64 and 33.6% Pb respectively. A 92.5% recovery of
      accumulated Pb from the immobilized biomass suggests that repeated absorption
      desorption is possible.

PMID- 21195609
TI  - Biosorption of tetradecyl benzyl dimethyl ammonium chloride on activated sludge:
      kinetic, thermodynamic and reaction mechanisms.
AB  - The biosorption of tetradecyl benzyl dimethyl ammonium chloride (C(14)BDMA) onto
      activated sludge was examined in aqueous solution with respect to the contact
      time, temperature and particle size. Equilibrium reached in about 2h contact
      time. An decrease in the temperature increases of biosorption capacity of
      C(14)BDMA onto activated sludge, which also increases with decreasing particle
      size. The experimental data fit the pseudo-second-order kinetics model well. The
      Langmuir and Freundlich models were applied to describe equilibrium isotherms,
      and the equilibrium partitioning data was described well by both models.
      Thermodynamic data showed that C(14)BDMA biosorption onto activated sludge was
      feasible, spontaneous and exothermic. The Fourier transform infrared (FT-IR)
      spectrophotometry results show that both physisorption and chemisorption were
      involved. The measured zeta potential values and the enhanced cation
      concentration indicate the presence of electrostatic interactions, hydrophobic
      interactions and ion exchange.

PMID- 21195610
TI  - Discovery of fused 5,6-bicyclic heterocycles as gamma-secretase modulators.
AB  - We herein report the discovery of four series of fused 5,6-bicyclic heterocycles
      as gamma-secretase modulators. Synthesis and SAR of these series are discussed.
      These compounds represent a new class of gamma-secretase modulators that
      demonstrate moderate to good in vitro potency in inhibiting Abeta(42) production.

PMID- 21195611
TI  - Modulation of PPAR subtype selectivity. Part 2: Transforming PPARalpha/gamma dual
      agonist into alpha selective PPAR agonist through bioisosteric modification.
AB  - A novel series of oxime containing benzyl-1,3-dioxane-r-2-carboxylic acid
      derivatives (6a-k) were designed as selective PPARalpha agonists, through
      bioisosteric modification in the lipophilic tail region of PPARalpha/gamma dual
      agonist. Some of the test compounds (6a, 6b, 6c and 6f) showed high selectivity
      towards PPARalpha over PPARgamma in vitro. Further, highly potent and selective
      PPARalpha agonist 6c exhibited significant antihyperglycemic and
      antihyperlipidemic activity in vivo, along with its improved pharmacokinetic
      profile. Favorable in-silico interaction of 6c with PPARalpha binding pocket
      correlate its in vitro selectivity profile toward PPARalpha over PPARgamma.
      Together, these results confirm discovery of novel series of oxime based
      selective PPARalpha agonists for the safe and effective treatment of various
      metabolic disorders.

PMID- 21195612
TI  - 8-Aza-7,9-dideazaxanthine acyclic nucleoside phosphonate inhibitors of thymidine
      phosphorylase.
AB  - 3- and 8-(8-phosphonooctyl)-8-aza-7,9-dideazaxanthine, and 1,8-bis(8-aza-7,9
      dideazaxanthin-8-yl)octane were prepared and found to inhibit thymidine
      phosphorylase from Escherichia coli, human recombinant TP expressed in V79, and
      TP purified from human placenta. The IC(50) values ranged from 3.5 to 27MUM.

PMID- 21195613
TI  - Chemical affinity matrix-based identification of prohibitin as a binding protein
      to anti-resorptive sulfonyl amidine compounds.
AB  - In order to identify the binding proteins to anti-resorptive 5-chloro-1-(2,6
      dimethylpiperidin-1-yl)-N-tosylpentan-1-imine (1), the chemical affinity matrix
      for the compound 1 (2b) was designed and synthesized. Using 2b-based chemical
      proteomics, prohibitin was identified as one of strong binding proteins for 2b.

PMID- 21195614
TI  - Pyrimido[4,5-d]azepines as potent and selective 5-HT2C receptor agonists: design,
      synthesis, and evaluation of PF-3246799 as a treatment for urinary incontinence.
AB  - New pyrimido[4,5-d]azepines 7 are disclosed as potent 5-HT(2C) receptor agonists.
      A preferred example, 7b had minimal activation at either the 5-HT(2A) or 5-HT(2B)
      receptors combined with robust efficacy in a preclinical canine model of stress
      urinary incontinence (SUI) and attractive pharmacokinetic and safety properties.
      Based on this profile, 7b (PF-3246799) was identified as a candidate for clinical
      development for the treatment of SUI. In addition, it proved to be critical to
      build an understanding of the translation between recombinant cell-based systems,
      native tissue preparations and in vivo preclinical models. This was a significant
      undertaking and proved to be crucial in compound selection.

PMID- 21195615
TI  - Imidazolylchromanone oxime ethers as potential anticonvulsant agents:
      Anticonvulsive evaluation in PTZ-kindling model of epilepsy and SAR study.
AB  - As a continuation of our efforts to develop the azolylchromanone derivatives as
      potential anticonvulsant agents, we explored (Z)- and (E)-oxime ether derivatives
      of imidazolylchromanones bearing different lipophilic O-benzyl groups and tested
      their anticonvulsant activities in PTZ-kindling model of epilepsy. O-(2,4
      Dichlorobenzyl) oximes 8a, 16a and 20a were significantly effective in delaying
      the onset of the PTZ-evoked seizures at the dose of 30mg/kg in kindled animals.
      The most effective compounds in delaying seizures were 7-chlorochromanone-O-(2,4
      dichlorobenzyl) oximes 8a and 20a. SAR studies showed that introduction of a
      chlorine atom to the 7-position and/or a methyl group to the 2-position of the
      chroman ring resulted in an improvement of anti-seizure efficacy in O-(2,4
      dichlorobenzyl) oxime series.

PMID- 21195616
TI  - A potent and selective indole N-type calcium channel (Ca(v)2.2) blocker for the
      treatment of pain.
AB  - N-type calcium channels (Ca(v)2.2) have been shown to play a critical role in
      pain. A series of low molecular weight 2-aryl indoles were identified as potent
      Ca(v)2.2 blockers with good in vitro and in vivo potency.

PMID- 21195617
TI  - Synthesis and structure-activity relationships of novel benzoxaboroles as a new
      class of antimalarial agents.
AB  - A series of boron-containing benzoxaborole compounds was designed and synthesized
      for a structure-activity relationship investigation surrounding 7
      (HOOCCH(2)CH(2))-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (1) with the goal of
      discovering a new antimalarial treatment. Compound 1 demonstrates the best
      potency (IC(50)=26nM) against Plasmodium falciparum and has good drug-like
      properties, with low molecular weight (206.00), low ClogP (0.86) and high water
      solubility (750MUg/mL at pH 7).

PMID- 21195618
TI  - Reversible demyelinating neuropathy associated with renal cell carcinoma.
AB  - Paraneoplastic neuropathy is a potential complication of renal cell carcinoma.
      The clinical and electrophysiologic features of such patients have not been well
      characterized. We describe a patient with a demyelinating neuropathy associated
      with papillary renal cell carcinoma that resolved following nephrectomy. The
      literature is reviewed with particular attention to the clinical,
      electrophysiologic, and kidney histopathologic characteristics of similar
      patients. Features arguing against other acquired demyelinating neuropathies are
      highlighted, and we conclude that abdominal imaging may provide important
      diagnostic data in some patients with evolving demyelinating neuropathies. The
      significance of papillary renal cell carcinoma (as opposed to clear renal cell
      carcinoma) is unknown, but may have important pathophysiologic implications.

PMID- 21195619
TI  - Recombinant expression of the AChR-alpha1 subunit for the detection of
      conformation-dependent epitopes in Myasthenia Gravis.
AB  - Detection of autoantibodies associated with neurological disease typically
      involves immunoprecipitation of radioactively labeled native proteins. We
      explored whether single receptor subunits, fused to Renilla luciferase (Ruc),
      could detect patient autoantibodies in Luciferase Immunoprecipitation Systems.
      Myasthenia Gravis patient sera were tested for conformational autoantibodies to
      only the alpha1-subunit of the nicotinic acetylcholine receptor (AChR). Using a
      panel of 10 AChR-alpha1 fragments, AChR-alpha1-Delta5-Ruc demonstrated the
      highest immunoreactivity with a conformational-specific antibody and the highest
      sensitivity in a pilot cohort. Testing a larger cohort with AChR-alpha1-Delta5
      Ruc demonstrated 21% sensitivity and 97% specificity. A point mutation within Ruc
      increased the diagnostic performance of AChR-alpha1-Delta5 (32% sensitivity, 97%
      specificity). The (125)I-alpha-bungarotoxin multi-subunit AChR assay demonstrated
      63% sensitivity and 97% specificity. These findings highlight the difficulty in
      detecting Myasthenia Gravis conformational epitopes across assay formats and lay
      the foundation for detecting autoantibodies to defined recombinant chains of the
      AChR and potentially other neurotransmitter receptors.

PMID- 21195620
TI  - The use of poly-lactic acid to improve projection of reconstructed nipple.
AB  - PURPOSE: Nipple-areola reconstruction represents an important step for final
      mammary reconstruction. Many techniques have been described. The drawback is the
      progressive nipple projection loss with time from 50% to over 70% of the initial
      projection. In this report, we evaluated the effect of injectable poly-lactic
      acid (PLLA) to improve projection of reconstructed nipples. RESULTS: We selected
      12 patients with a residual nipple projection between 0.1 and 2 mm. The patients
      were injected locally inside the nipple with 0.5 ml of PLLA (dilution 1:4) every
      4 weeks for 4 times. At the study end, patients were satisfied with results. No
      adverse effects were observed. After one year, an increase of nipple projection
      ranging from 0.5 to 3.5 mm was obtained with an average increase of 2.3 mm (282%)
      and this variation was statistically significant (p < 0.0001). CONCLUSION: The
      use of injectable PLLA is a simple and effective procedure to improve projection
      of reconstructed nipple.

PMID- 21195622
TI  - Towards echinomycin mimetics by grafting quinoxaline residues on glycophane
      scaffolds.
AB  - Echinomycin is a natural depsipeptide, which is a bisintercalator, inserting
      quinoxaline units preferentially adjacent to CG base pairs of DNA. Herein the
      design and synthesis of echinomycin mimetics based on grafting of two quinoxaline
      residues onto a macrocyclic scaffold (glycophane) is addressed. Binding of the
      compounds to calf-thymus DNA was studied using UV-vis and steady state
      fluorescence spectroscopy, as well as thermal denaturation. An interesting
      observation was enhancement of fluorescence emission for the peptidomimetics on
      binding to DNA, which contrasted with observations for echinomycin. Molecular
      dynamics simulations were exploited to explore in more detail if bis
      intercalation to DNA was possible for one of the glycophanes. Bis-intercalating
      echinomycin complexes with DNA were found to be stable during 20ns simulations at
      298K. However, the MD simulations of a glycophane complexed with a DNA octamer
      displayed very different behaviour to echinomycin and its quinoxaline units were
      found to rapidly migrate out from the intercalation site. Release of bis
      intercalation strain occurred with only one of the quinoxaline chromophores
      remaining intercalated throughout the simulation. The distance between the
      quinoxaline residues in the glycophane at the end of the MD simulation was 7.3
      7.5A, whereas in echinomycin, the distance between the residues was ~11A,
      suggesting that longer glycophane scaffolds would be required to generate bis
      intercalating echinomycin mimetics.

PMID- 21195621
TI  - Assortment and packaging of the segmented rotavirus genome.
AB  - The rotavirus (RV) genome comprises 11 segments of double-stranded RNA (dsRNA)
      and is contained within a non-enveloped, icosahedral particle. During assembly, a
      highly coordinated selective packaging mechanism ensures that progeny RV virions
      contain one of each genome segment. Cis-acting signals thought to mediate
      assortment and packaging are associated with putative panhandle structures formed
      by base-pairing of the ends of RV plus-strand RNAs (+RNAs). Viral polymerases
      within assembling core particles convert the 11 distinct +RNAs to dsRNA genome
      segments. It remains unclear whether RV +RNAs are assorted before or during
      encapsidation, and the functions of viral proteins during these processes are not
      resolved. However, as reviewed here, recent insights gained from the study of RV
      and two other segmented RNA viruses, influenza A virus and bacteriophage Phi6,
      reveal potential mechanisms of RV assortment and packaging.

PMID- 21195623
TI  - Reverse facial artery-submental artery deepithelialised submental island flap to
      reconstruct maxillary defects following cancer ablation.
AB  - OBJECTIVE: The present study assessed the reliability of the reverse facial
      artery-submental artery deepithelialised submental island technique to
      reconstruct maxillary defects. METHODS: The study included 13 patients (9 men and
      4 women; 43-62 years) with maxillary defects resulting from cancer ablation. Ten
      patients presented with maxillary gingival squamous cell carcinoma and the
      remaining 3 cases were hard palate squamous cell carcinomas. The maxilla was
      resected and the remaining defects were classified as Class 2a. Reverse facial
      artery-submental artery deepithelialised submental island flaps measuring 8-10 cm
      in length and 4-5 cm in width were used to reconstruct the defects. RESULTS:
      Twelve of the 13 flaps survived. No donor-site problems or palsy of the marginal
      mandibular branch of the facial nerve occurred. The follow-up period ranged from
      8 to 24 months, 1 patient died as a result of local tumour recurrence and 2
      patients developed cervical recurrence. CONCLUSION: The reverse facial artery
      submental artery deepithelialised submental island flap is safe, quick and simple
      to use or elevate. The flap is a reliable technique for reconstructing maxillary
      defects following cancer ablation.

PMID- 21195624
TI  - Seven-year institutional experience in the surgical treatment of orbito-zygomatic
      fractures.
AB  - INTRODUCTION: Facial trauma is a common injury in the urban setting. Many studies
      have been published on the epidemiology of facial fractures, but few of them
      conducted in Brazil. The purpose of this study was to analyze the epidemiological
      characteristics of patients treated for orbito-zygomatic fractures at our
      institution. METHODS: Retrospective analysis of 141 patients with orbito
      zygomatic complex fractures who underwent surgical treatment between May 2001 and
      May 2008. RESULTS: The population studied consisted mostly of males (86.5% of
      patients), with a male:female ratio of 6.4:1. A marked predominance of patients
      aged 21-30 years was observed (34.3%). Traffic-related causes were the most
      common, with motorcycle accidents as the most frequent aetiology (24.8% of
      patients), followed by car accidents (19.2%) and interpersonal violence (15.2%).
      Associated injuries accounted for 88 lesions in 65 patients, and their occurrence
      was statistically associated with traffic-related causes. All patients enrolled
      in the study were managed with operative treatment. The most utilized method for
      treatment was internal fixation with miniplates and screws (83.7% of the cases).
      The complication rate was 24.8%. CONCLUSION: Orbito-zygomatic fractures can cause
      significant morbidity and impairment in patients' quality of life. Despite recent
      improvements in legislation and educational campaigns, traffic remains the main
      cause of these injuries. More intensive efforts should be made in order to reduce
      its impact in the aetiology of facial trauma.

PMID- 21195625
TI  - Giant trigeminal schwannoma with parapharyngeal extension: report of a case.
AB  - The authors present their experience in the treatment of a giant trigeminal
      schwannoma with wide extension in the parapharyngeal space using a combination of
      the orbito-zygomatic and the transcervical-transmandibular approaches. The
      clinical and radiological findings, advantages of surgical approach and clinical
      outcome will be discussed.

PMID- 21195626
TI  - Psychological care for maxillofacial trauma patients: a preliminary survey of
      oral and maxillofacial surgeons.
AB  - INTRODUCTION: Psychological morbidities are major complications following
      maxillofacial injuries. The aim of this study was to assess self-evaluation of
      oral and maxillofacial surgeons on posttraumatic psychological care. METHODS:
      Using a cross-sectional study design, we enrolled a sample of surgeons in 261
      oral and maxillofacial surgery (OMFS) departments in the United States, United
      Kingdom and France. A self-administered e-mail questionnaire was used to evaluate
      knowledge, attitude and practice of the surgeons regarding psychological problems
      in maxillofacial injury patients, and their collaboration with psychological
      personnel. Appropriate descriptive and univariate statistics were computed, and
      P<0.05 was considered statistically significant. RESULTS: The response rate was
      28.1% (112 of 398), but we included only 100 respondents from 107 OMS units. 60%
      of the surgeons disclosed a moderate or high level of relevant knowledge. Only 28
      OMS departments (26.2%) had intra-service psychological staff (commonly in France
      [P<0.05]), and five surgeons revealed considerable deficits in access to
      psychological care. Frequent reasons for patient referral to psychological staff
      were depression, body dysmorphic disorder, posttraumatic stress disorder,
      suicidal idea, anxiety and behavioural changes. Eighty-eight surgeons linked
      patient's non-compliance with changes or difficulties in practice, and 58
      surgeons experienced it already. CONCLUSIONS: Despite several limitations, the
      results of this study suggest that oral and maxillofacial surgeons have a great
      interest and experience in posttraumatic psychological problems. Psychological
      professionals in charge will improve surgical care quality. Well-designed studies
      with larger sample size are desirable to confirm our results. Ethical issues of
      maxillofacial trauma care are also discussed.

PMID- 21195627
TI  - Maxillary-driven simultaneous maxillo-mandibular distraction for hemifacial
      microsomia.
AB  - We treat hemifacial microsomia with a combination of surgery and orthodontic
      treatment during the growth period, resulting in early improvement in facial
      asymmetry and the induction of normal growth. We previously used gradual
      distraction of the mandibular ramus for Pruzansky's type II classification
      (Pruzansky, 1969). In type II cases, the maxilla should also be treated actively
      as, using this technique, improvement of the occlusal plane is difficult to
      achieve, resulting in a cross bite and difficulties in post-operative orthodontic
      treatment-especially in older patients. Morphologically, the mandibular angle
      region of the operative side is flat, and the angle of the mouth remains
      elevated. We performed mandibular-driven simultaneous maxillo-mandibular
      distraction while the occlusion was maintained using intermaxillary anchorage.
      However, mandibular-driven distraction tended to elongate the face because the
      mandible only elongated downwards and the mandibular ramus did not reach the
      glenoid. Furthermore, external distraction devices produce significant distress
      for patients until removal of the device and cause scars on the face. We
      developed a new internal distraction device with a variable angle and performed
      maxillary-driven simultaneous maxillo-mandibular distraction using this device.
      The result was morphologically satisfactory and solved the above problems.
      Because the patient was in the growth period, careful follow-up and induction to
      normal growth were important while the inferior growth of the affected side was
      monitored.

PMID- 21195628
TI  - Reduced force steadiness in women with neck pain and the effect of short term
      vibration.
AB  - This study compares neck force steadiness in women with neck pain and controls
      and the way this is influenced by short term vibration of the neck. In the first
      experiment, 9 women with chronic neck pain and 9 controls performed 10-s
      isometric cervical flexion at 15N. Intramuscular EMG was recorded from the
      sternocleidomastoid muscle. In the second experiment, 10 women with neck pain and
      10 controls performed 10-s isometric cervical flexion at 25% of their maximal
      force before and after vibration to the neck (bursts of 50Hz with duration 20,
      40, 60 and 120s). Surface EMG was acquired from the sternocleidomastoid and
      splenius capitis. In both experiments, force steadiness was characterized by the
      coefficient of variation (CoV) and the relative power in three frequency subbands
      (low: 0-3Hz; middle: 4-6Hz; high: 8-12Hz) of the force signal. Women with neck
      pain exhibited decreased force steadiness (Exp 1: patients 3.9+/-1.3%, controls
      2.7+/-0.9%, P<0.05; Exp 2: patients 3.4+/-1.2%, controls 1.7+/-0.6%, P<0.01)
      which was associated with higher power in the low-frequency band (patients 71.2+/
      9.6%, controls 56.7+/-9.2%, P<0.01). Following vibration, CoV (2.6+/-1.1%,
      P<0.05) and the power in the low-frequency band of the force signal decreased
      (63.1+/-13.9%, P<0.05) in the patient group. These effects were not present in
      controls. Motor unit behavior and surface EMG amplitude were similar between
      groups. In conclusion, women with neck pain have reduced force steadiness, likely
      due to alterations in Ia afferent input. Vibration, which modulates Ia afferent
      input, increases force steadiness in patients with neck pain.

PMID- 21195629
TI  - Differences in time-frequency representation of lower limbs myoelectric activity
      during single and double leg landing in male athletes.
AB  - This study compared the instantaneous median frequency (IMF) obtained by means of
      a Choi-Williams transform of an electromyogram of the lower-limb muscles during
      single-leg (SL) and double-leg (DL) landings performed by fifteen male athletes.
      The IMF values of the rectus femoris (RF), biceps femoris (BF) and hip adductors
      (HA) were compared between two landing tasks, within each landing, and before and
      after ground contact (GC). The IMF values of the RF did not change between
      landings in contrast to those of the BF, which presented from 20- to 40-ms higher
      SL values before GC and from 40 to 60 ms after GC. HA presented higher SL values
      during the 40-60 ms range before GC. Within each landing, the RF IMF decreased
      from 40 ms to 60 ms after GC in the SL. Similar results were found for the HA
      IMF, which decreased from 40ms to 80 ms after GC. The BF IMF showed no
      significant change. These results suggest muscle recruitment related to anterior
      cruciate ligament protection since the IMF values of the RF decreased in the SL,
      whereas the BF IMF increased. Results for the HA showed the importance of hip
      muscles in stabilizing the core region, allowing the activation of distal muscles
      with greater safety.

PMID- 21195630
TI  - Pyogenic abscess after hepatic artery embolization: a rare but potentially lethal
      complication.
AB  - PURPOSE: Hepatic artery embolization (HAE) is used commonly to treat liver tumors
      or hemorrhage. Infectious complications are rare but carry high rates of
      morbidity and mortality. Identification of clinical factors associated with
      postembolization abscess may improve management and outcome. MATERIALS AND
      METHODS: Clinical and pathologic variables of patients treated with HAE were
      collected and analyzed to determine the etiology, incidence, and outcome of
      pyogenic hepatic abscess. RESULTS: From January 1998 to January 2010, 971
      patients underwent 2,045 HAE procedures. Fourteen patients developed a pyogenic
      hepatic abscess after embolization, for an overall rate of 1.4%. Thirty-four
      patients (4%) had a history of bilioenteric anastomosis (BEA) and 21 patients
      (2%) lacked a competent sphincter of Oddi because of the presence of a biliary
      stent (n = 19) or a previous sphincterotomy (n = 2). Eleven of the 34 patients
      with a BEA (33%) and two of 21 patients with an incompetent sphincter (10%)
      developed abscesses, in contrast to only one abscess (0.05%) among the 916
      patients with apparently normal sphincters (0.1%; odds ratio, 437.6; 95% CI, 54.2
      3,533; P < .0001). Gram-negative and Gram-positive aerobes were the most common
      bacteria isolated after drainage. Percutaneous drainage was the initial
      management strategy in all patients; two patients (14%) required subsequent
      surgical drainage and hepatectomy, and three (21%) died. CONCLUSIONS: Pyogenic
      hepatic abscess is rare after HAE. A history of BEA or an incompetent sphincter
      of Oddi caused by a biliary stent or previous sphincterotomy substantially
      increases the likelihood of this highly morbid and potentially fatal
      complication.

PMID- 21195631
TI  - Initial anesthetic experience during combined epicardial-endocardial treatment of
      atrial fibrillation.

PMID- 21195632
TI  - An incidental discovery or an impending disaster in a patient with coronary
      artery disease?

PMID- 21195633
TI  - Nondisplaced proximal humeral fractures: high incidence among outpatient-treated
      osteoporotic fractures and severe impact on upper extremity function and patient
      subjective health perception.
AB  - BACKGROUND: Although most proximal humeral fractures are attributed to
      osteoporosis, they are usually not considered individually in osteoporotic
      studies because of their lower incidence. The purpose of this study was to
      evaluate the incidence of nondisplaced proximal humeral fractures in comparison
      with other outpatient-treated osteoporotic fractures, as well as to assess their
      functional impact and effects on patient-perceived quality of life. MATERIALS AND
      METHODS: In this multicenter, cross-sectional, prospective study, all
      osteoporotic fractures in postmenopausal women aged 50 years or older treated
      nonoperatively in 358 trauma centers were recorded during a 3-month period.
      Fractures were considered osteoporotic if caused by a low-energy trauma.
      Pathologic fractures were excluded. The incidence of proximal humeral fractures
      in relation to other osteoporotic fractures was calculated. Patients were
      interviewed by telephone 6 months after the fracture with the Disabilities of the
      Arm, Shoulder and Hand and EuroQoL 5D questionnaires. RESULTS: This study
      comprised 5,147 women (mean age, 72.6 +/- 7.5 years) with 5,268 fractures. Of
      these, 912 (17.5%) had had proximal humeral fractures. The mean Disabilities of
      the Arm, Shoulder and Hand score was 26.6 +/- 25.7. Of the women, 67.3% had pain
      or discomfort and disclosed significant reductions in functional capacity,
      especially with regard to self-care (44.5%), daily life activities (56.5%), and
      anxiety or depression (32.7%). CONCLUSION: Nondisplaced proximal humeral
      fractures are among the most common fractures associated with osteoporosis, and
      they can be a major cause of functional disability and reduction in subjective
      patient-perceived health.

PMID- 21195634
TI  - Acromioclavicular joint injuries: indications for treatment and treatment
      options.

PMID- 21195635
TI  - Anteromedial radial head fracture-dislocation associated with a transposed biceps
      tendon: a case report.

PMID- 21195636
TI  - Convulsive status epilepticus in children: etiology, treatment protocol and
      outcome.
AB  - This study aimed to determine the etiology, treatment protocol and outcome of
      convulsive status epilepticus (SE) in children. An institutional treatment
      protocol using benzodiazepines (diazepam and midazolam) was assessed in a
      retrospective case study. The treatment protocol (Ege Pediatric Status
      Epilepticus Protocol or EPSEP) was developed based on an operational definition
      of pediatric SE according to the duration of seizure activity. Pediatric SE is
      divided into three categories: initial SE (20-30 min), established SE (30-60 min)
      and refractory SE (>60 min). Eight (30%) of the studied episodes were initial SE,
      10 (37%) were established SE, and 9 (33%) were refractory SE. With respect to the
      etiological spectrum of SE, 11 (40%) children had meningitis or encephalitis.
      Febrile SE was identified in 7 (26%) patients. Only 2 episodes of initial SE
      (7.5%) were controlled with first step of the protocol (two concomitant-doses of
      rectal diazepam). Midazolam bolus and infusions (up to 1.2 MUg/kg/min) were used
      to treat 22 episodes of SE (9 refractory SE, 10 established SE and 3 initial SE).
      Complete arrest of convulsive SE was achieved in 21 of 22 (95%) episodes with
      midazolam infusion. We concluded that the combined use of benzodiazepines
      (diazepam+midazolam) was safe and effective in the treatment of convulsive SE in
      children.

PMID- 21195637
TI  - Femoropopliteal balloon angioplasty vs. bypass surgery for CLI: a propensity
      score analysis.
AB  - OBJECTIVES: To compare the outcomes of femoropopliteal percutaneous transluminal
      angioplasty (PTA) and bypass surgery for critical limb ischaemia (CLI). DESIGN:
      The study is retrospective in nature. MATERIALS AND METHODS: This study included
      858 consecutive patients, who underwent femoropopliteal revascularisation for CLI
      at Helsinki University Central Hospital during 2000-2007. As many as 517 patients
      (60%) underwent PTA and 341 (40%) bypass surgery. Propensity score analysis was
      used for risk adjustment in multivariable analysis and for one-to-one matching.
      RESULTS: In the overall series, PTA had poorer long-term results than bypass (5
      year leg salvage, 78.2% vs. 91.8%, p < 0.0001; survival 49.2% vs. 57.1%, p =
      0.048; amputation-free survival, 42.0% vs. 53.7%, p = 0.003; freedom from
      surgical re-intervention 86.2% vs. 94.3%, p < 0.0001). When treatment method was
      adjusted for propensity score as well as in the propensity score-matched pairs,
      leg salvage and freedom from surgical re-intervention were worse after PTA than
      after bypass (among the 241 propensity score-matched pairs, 74.3% vs. 88.2%, p =
      0.031, and 86.1% vs. 89.8%, p = 0.025, respectively). Differences in survival,
      amputation-free survival and freedom from any re-intervention were not observed.
      CONCLUSIONS: In CLI patients, femoropopliteal PTA seems to be associated with
      poorer long-term leg salvage and freedom from surgical re-intervention than
      bypass surgery. However, the treatment method did not affect long-term amputation
      free survival.

PMID- 21195638
TI  - Endovascular aneurysm repair - to avoid rupture or to improve quality of life?

PMID- 21195639
TI  - Non-contrast computed tomography is comparable to contrast-enhanced computed
      tomography for aortic volume analysis after endovascular abdominal aortic
      aneurysm repair.
AB  - OBJECTIVES: To evaluate whether non-contrast computed tomography (NCCT) images
      are as reliable as contrast-enhanced computed tomography (CECT) images for the
      measurement of aortic volume (AV). MATERIALS AND METHODS: A total of 316 pairs of
      AVs were retrospectively measured from 316 consecutive patients, who underwent
      endovascular aneurysm repair (EVAR). A standardised multidetector computed
      tomography protocol was used to obtain precontrast, arterial and delay-phase
      images. A single blinded, experienced observer measured the AV from the lowest
      renal artery to the aortic bifurcation by means of the disc-summation method,
      using the precontrast and arterial-phase images. A second blinded observer
      measured the AV again in 16 randomly chosen cases. RESULTS: Both NCCT and CECT
      yielded similar AVs that were highly correlated (r(2) = 0.99; P < 0.0001). Bland
      and Altman analysis revealed a small bias (mean +/- 2 standard deviations: -0.9
      +/- 8 ml). The intraclass correlation coefficients (all >0.99; P < 0.0001) and
      low repeatability coefficients indicated that the AVs were reproducible with both
      methods. CONCLUSIONS: The AVs measured from NCCT images were accurate and highly
      reproducible compared with those from CECT images. Therefore, NCCT can be a
      reasonable alternative to CECT for AV assessment after EVAR. This is particularly
      important for patients with renal insufficiency (potentially sparing them from
      nephrotoxic contrast agents and unnecessary radiation) or allergy to contrast
      agents.

PMID- 21195640
TI  - Annexin A1 expression in atherosclerotic carotid plaques and its relationship
      with plaque characteristics.
AB  - OBJECTIVE: Annexin A1, a calcium and phospholipid-binding protein, is an
      important endogenous modulator of inflammation. Whether this regulatory role
      extends to atherosclerosis is unknown. The aim of this study is to investigate
      the genetic and protein expression of Annexin A1 in carotid endarterectomy
      specimens from patients with significant carotid stenosis. MATERIALS AND METHODS:
      The echogenicity of atherosclerotic plaques was determined by ultrasound prior to
      carotid endarterectomy (CEA) in 34 consecutively recruited patients with carotid
      stenosis exceeding 70%. The Annexin A1 messenger RNA and protein expression of
      the corresponding plaques obtained from those patients were analyzed by reverse
      transcriptase polymerase chain reaction (RT-PCR) and the immunohistochemical
      method respectively. Results were analyzed with respect to plaque characteristics
      and symptomatic disease. RESULTS: There were 25 males and 9 females, with a mean
      age of 68.8. Ten patients were asymptomatic. The symptomatic patients' plaques
      were more echolucent (mean grey scale median (GSM) of 103) than those of
      asymptomatic patients (mean GSM = 126, p = 0.022). The Annexin A1 protein was
      constitutively expressed in all plaques, and Annexin A1 gene expression was
      statistically higher in patients with asymptomatic disease compared with those
      with neurological symptoms (87 +/- 4% vs. 42 +/- 6.2%; p < 0.001, unpaired t
      test). The GSM score was positively correlated with Annexin A1 levels in patients
      with high-grade carotid artery stenosis (r = 0.501, p = 0.009). CONCLUSIONS: This
      is the first study to suggest that high Annexin A1 expression may have a
      stabilising effect in asymptomatic patients with less echolucent atherosclerotic
      plaques. Since atherosclerosis is an inflammatory process, we further postulate
      that Annexin A1 may play an essential role in preventing plaque complications or
      disease progression.

PMID- 21195641
TI  - Aortic surgery complications evaluated by an implanted continuous
      electrocardiography device: a case report.
AB  - INTRODUCTION: Cardiac arrhythmias are a major cause for morbidity and mortality
      in patients undergoing non-cardiac vascular surgery. REPORT: An implantable loop
      recorder (Reveal((r)) XT) was used for continuous heart rhythm monitoring to
      detect perioperative arrhythmias in a 69-year-old man undergoing major vascular
      surgery for an infected aortobifemoral prosthesis. The Reveal((r)) detected
      several episodes of asymptomatic new-onset atrial fibrillation postoperatively,
      associated with elevated serum levels of troponin-T and N-terminal pro-B-type
      natriuretic peptide NT-proBNP). DISCUSSION: Continuous heart rhythm monitoring
      with assessment of serum cardiac biomarkers may allow early identification and
      treatment of patients at high risk of perioperative cardiovascular complications,
      in particular, cardiac arrhythmias.

PMID- 21195642
TI  - Clinical application of free anterolateral thigh flap in the reconstruction of
      intraoral defects.
AB  - OBJECTIVE: The purpose of this study was to assess the clinical features and
      therapeutic efficacy of the intraoral defects reconstruction with 3 types of
      anterolateral thigh flaps. STUDY DESIGN: The clinicopathologic data of 39 cases
      with oral tumors were obtained from the School of Stomatology, Nanjing University
      Medical Center, from December 2008 to June 2010. These patients underwent the
      simultaneous tumor resection and intraoral defects reconstruction with free
      anterolateral thigh flaps. RESULTS: There were 22 male and 17 female patients;
      the ratio of male to female was 1.3:1; the mean age was 56.1 years. Twenty-two of
      the anterolateral thigh flaps were musculocutaneous flaps (56.4%), 8 were
      fasciocutaneous flaps (20.5%), and 9 were ultrathin flaps (23.1%). Five patients
      required operative exploration in the perioperative period. Three flaps were
      thrombotic events, 1 flap was hematoma, and 1 flap was twisting of perforator.
      After the salvages, 1 flap was partial failure, 1 flap was total failure, and the
      other 3 flaps were complete survival. CONCLUSIONS: The free anterolateral thigh
      flap was the ideal soft tissue flap in the intraoral defects reconstruction. This
      flap presents good functional results at the receiving site with the additional
      advantages of minimal donor-site morbidity and a high level of patient
      satisfaction.

PMID- 21195643
TI  - Nasal continuous positive airway pressure (nCPAP) treatment for obstructive sleep
      apnea, road traffic accidents and driving simulator performance: a meta-analysis.
AB  - We used meta-analysis to synthesize current evidence regarding the effect of
      nasal continuous positive airway pressure (nCPAP) on road traffic accidents in
      patients with obstructive sleep apnea (OSA) as well as on their performance in
      driving simulator. The primary outcomes were real accidents, near miss accidents,
      and accident-related events in the driving simulator. Pooled odds ratios (ORs),
      incidence rate ratios (IRRs) and standardized mean differences (SMDs) were
      appropriately calculated through fixed or random effects models after assessing
      between-study heterogeneity. Furthermore, risk differences (RDs) and numbers
      needed to treat (NNTs) were estimated for real and near miss accidents. Meta
      regression analysis was performed to examine the effect of moderator variables
      and publication bias was also evaluated. Ten studies on real accidents (1221
      patients), five studies on near miss accidents (769 patients) and six studies on
      the performance in driving simulator (110 patients) were included. A
      statistically significant reduction in real accidents (OR=0.21, 95% CI=0.12-0.35,
      random effects model; IRR=0.45, 95% CI=0.34-0.59, fixed effects model) and near
      miss accidents (OR=0.09, 95% CI=0.04-0.21, random effects model; IRR=0.23, 95%
      CI=0.08-0.67, random effects model) was observed. Likewise, a significant
      reduction in accident-related events was observed in the driving simulator (SMD=
      1.20, 95% CI=-1.75 to -0.64, random effects). The RD for real accidents was -0.22
      (95% CI=-0.32 to -0.13, random effects), with NNT equal to five patients (95%
      CI=3-8), whereas for near miss accidents the RD was -0.47 (95% CI=-0.69 to -0.25,
      random effects), with NNT equal to two patients (95% CI=1-4). For near miss
      accidents, meta-regression analysis suggested that nCPAP seemed more effective
      among patients entering the studies with higher baseline accident rates. In
      conclusion, all three meta-analyses demonstrated a sizeable protective effect of
      nCPAP on road traffic accidents, both in real life and virtual environment.

PMID- 21195644
TI  - Finite element analysis of a novel pin-sleeve system for external fixation of
      distal limb fractures in horses.
AB  - The transfixation pin cast (TPC) is an external skeletal fixation technique used
      to treat horses with distal limb fractures, but its use is often associated with
      pin-loosening and an increased risk of treatment failure. To address implant
      loosening, the pin sleeve cast system (PSC) was recently designed and consists of
      a pin-sleeve unit inserted into the bone. Each pin runs through a sleeve placed
      in the bone, making contact at two fixed points only within the sleeve. Each pin
      is attached to a ring embedded in a resin cast. In this report, the mechanical
      performance of a traditional TPC pin arrangement was compared with that of the
      PSC using validated finite element models of bone substitutes previously tested
      in vitro. The PSC resulted in a marked reduction in peak strain magnitude around
      the pins and a more even distribution of strain across the bone cortex. The two
      systems resulted in comparable proximal fragment displacement and had a similar
      stress concentration around bone defects during implant removal. The findings
      suggest that the PSC load transfer mechanism is effective even in geometrically
      complex structures like equine bones.

PMID- 21195645
TI  - The influence of animals on the development of children.
AB  - There is a widespread belief that interaction with an animal is beneficial for
      the development of children, and several studies (most with methodological
      shortcomings) have investigated the influence of (companion) animals on the
      social-emotional and cognitive development of children. In this article, the 1984
      model of Professor Jay Belsky has been used to describe which variables influence
      the development of children and how the companion animal-child interaction
      influences these variables. The value of the AAA/AAT (Animal Assisted
      Activities/Animal Assisted Therapy) programmes in children with a wide variety of
      clinical and social problems, such as behaviour problems and autistic spectrum
      symptoms, is discussed. The findings suggest that (companion) animals positively
      influence children's development and have a valuable role in therapy.

PMID- 21195646
TI  - Differences in activity-related behaviour among patients with chronic low back
      pain.
AB  - The aim of the present study was to compare the subjectively reported and
      objectively assessed activity-related characteristics of patients with Chronic
      Low Back Pain (CLBP) who were classified according to their scores on the
      Patterns of Activity Measure-Pain (POAM-P) into avoiders, persisters, mixed
      performers (i.e. high scores on both avoidance and persistence behaviour) or
      functional performers (i.e. low scores on avoidance and persistence behaviour).
      Patients carried an electronic diary during 14 days to assess the self-reported
      activity and pain intensity levels in daily life. An accelerometer was used to
      objectively assess their activity level during the same time period. Results were
      available for 79 patients. Avoiders, persisters and mixed performers showed a
      higher level of self-reported disability than functional performers. Avoiders
      were characterized by a low level of self-reported habitual activities and
      persisters by long objectively measured daily uptime. The objectively assessed
      level of physical activity did not differ between the four groups. A further
      analysis tested the association between pain intensity levels and self-reported
      and objectively assessed daily life activity levels in avoiders and persisters.
      In persisters, a higher level of self-reported activities in daily life was
      related to increased pain. The objectively assessed activity level was not
      associated with pain intensity.

PMID- 21195647
TI  - New insights into silica-based NMR "chromatography".
AB  - Silica is used as an important component for NMR "chromatography". In this study
      the effect of the binding strength to silica of a variety of compounds on their
      diffusion rate is measured for the first time. Over two orders of magnitude of
      diffusion difference enhancement was obtained in the presence of silica for some
      compounds. An explanation of the enhancement is given that also allows one to
      predict the "chromatographic" behavior of new compounds or mixtures. The binding
      strength is divided into categories of weakly bound, singly bound and multiply
      bound. Carboxylates, sulfonates, and diols are found to be particularly strongly
      bound and to diffuse up to 21/2 orders of magnitude more slowly in the presence
      of silica.

PMID- 21195648
TI  - Impairment of methyl cycle affects mitochondrial methyl availability and
      glutathione level in Down's syndrome.
AB  - In Down's syndrome there is evidence that increased gene expression coding for
      specific cystathionine beta-synthase translates directly into biochemical
      aberrations, which result in a biochemical and metabolic imbalance of the methyl
      status. This event is destined to impact mitochondrial function since methylation
      is a necessary event in mitochondria and relies on the availability and uptake of
      the methyl donor S-adenosylmethionine. Indeed mitochondrial dysfunctions have
      been widely described in Down's syndrome, but they have never been correlated to
      a possible mitochondrial methyl unbalance. In the present study we find that the
      mitochondrial levels of S-adenosylmethionine are reduced in Down's syndrome
      compared to control cells demonstrating the effect of the methyl unbalance on
      mitochondria. The possible role of methylation in mitochondria is discussed and
      some preliminary results on a possible methylation target are presented.

PMID- 21195649
TI  - Elevated concentrations of sedoheptulose in bloodspots of patients with
      cystinosis caused by the 57-kb deletion: implications for diagnostics and
      neonatal screening.
AB  - Cystinosis is an autosomal recessive lysosomal storage disease caused by
      mutations in CTNS. The most prevalent CTNS mutation is a homozygous 57-kb
      deletion that also includes an adjacent gene named SHPK (CARKL), encoding
      sedoheptulokinase. Patients with this deletion have elevated urinary
      concentrations of sedoheptulose. Using derivatisation with pentafluorobenzyl
      hydroxylamine and liquid chromatography-tandem mass spectrometry (LC-MS/MS), we
      developed a new sensitive method for the quantification of sedoheptulose in dried
      blood spots. This method can be utilized as a quick screening test to detect
      cystinosis patients homozygous for the 57-kb deletion in CTNS; which is the most
      common mutation of cystinosis. Sedoheptulose concentrations in the deleted
      patients were 6 to 23 times above the upper limit for controls. The assessment of
      sedoheptulose in a bloodspot from a known cystinosis patient homozygous for the
      57-kb deletion retrieved from the Dutch neonatal screening program showed that
      sedoheptulose was already elevated in the neonatal period. There was no overlap
      in sedoheptulose levels between cystinosis patients homozygous for the 57-kb
      deletion and cystinosis patients not homozygous for this deletion. Our presented
      method can be used prior to mutation analysis to detect cystinosis patients
      homozygous for the 57-kb deletion. We feel that the presented method enables fast
      (pre)-symptomatic detection of cystinosis patients homozygous for the 57-kb
      deletion, allowing early treatment.

PMID- 21195651
TI  - Suicidal and criminal immolations: an 18-year study and review of the literature.
AB  - We aimed to examine our autopsy data in order to analyze epidemiological and
      injury characteristics in criminal and suicidal immolation cases. During the 18
      year period, we recorded 29 suicides and three homicides due to fire burns. In
      suicide group there was a majority of men (gender ratio: 3.1:1) and the mean age
      was 42.8 years (range 20-72). In the homicide group, the victims were two men and
      one woman. Their mean age was 44 years (range 39-54). The location of self
      immolation was mostly the deceased's car or home and most suicides happened
      during the evening and the night. The main frequent motives for self-immolation
      were affective problems, financial problems, or both. One or several flammable
      fluids, usually petrol or alcohol, were used in 18 suicide cases and in one
      homicide. The median total body surface area burnt was 79.3% (range 10-100%) in
      self inflicted group and 83.3% (range 50-100%) in assault group. The sole of the
      feet was spared in all suicide cases. Blood CO-Hb level was measured in 27 self
      immolation cases. It ranged between 1% and 10% in 11 cases and was superior to
      10% in the remaining. Twenty-three self-immolation victims and one homicide
      victim had soot in their respiratory tracts. Soot in the respiratory tracts was
      associated to soot in the digestive tracts in six cases. Alcohol and drugs
      intoxication played a minor role. In six cases, the victim associated self
      incineration with one or more other methods of suicide (complex suicides). The
      presence of associated trauma raises the problem of vitality and interpretation
      of the lesions in determining the manner of death.

PMID- 21195650
TI  - Melioidosis presenting as sepsis syndrome: a case report.
AB  - Melioidosis is an important disease in Asia and Australia. It is very rare in
      Venezuela. We describe the case of a 50-year-old diabetic patient with several
      episodes of right tibial osteomyelitis, left shoulder arthritis, sternal
      osteomyelitis, right parietal osteomyelitis, and subperiosteal abscess, followed
      by septic arthritis of the right knee. In all cases Gram stain smear showed Gram
      negative bacilli. Culture yielded Burkholderia pseudomallei, susceptible to third
      and fourth-generation cephalosporins, ciprofloxacin and aztreonam, and resistant
      to aminoglycosides. He developed sepsis syndrome. Blood cultures and culture of
      abscess and joint fluids also revealed B. pseudomallei. The patient was treated
      with ceftazidime and ciprofloxacin, then cefepime and trimethoprim
      sulfamethoxazole. He was discharged with suppressive therapy consisting of oral
      doxycycline and trimethoprim-sulfamethoxazole, and follow-up has continued to
      date. At this time he remains asymptomatic. Melioidosis is an extremely rare
      disease in our country. To our knowledge, this is only the second case reported
      in Venezuela.

PMID- 21195652
TI  - Amyloid and glucose imaging in dementia with Lewy bodies and multiple systems
      atrophy.
AB  - BACKGROUND: Multiple Systems Atrophy (MSA) and Dementia with Lewy bodies (DLB)
      can present with both REM behavior disorder and severe autonomic dysfunction. In
      rare occasions, patients with MSA progress to cognitive impairment and even
      dementia. Positron emission topography (PET) imaging using both the amyloid
      ligand Pittsburgh Compound B (11C-PiB) and 18 flurodeoxyglucose (18F-FDG) was
      used to ascertain the presence of amyloid and pattern of glucose metabolic
      derangement in both disorders. METHODS: Patients diagnosed with probable DLB or
      MSA, with clinical symptoms of either REM Behavior Disorder (RBD), Parkinsonism,
      or dysautonomia were prospectively identified. All underwent both 11C-PiB and 18F
      FDG PET imaging. Statistical comparison between DLB, MSA, and normal controls was
      performed. RESULTS: Six patients, 3 with DLB, 2 with Parkinson predominant MSA
      (MSA-P), and 1 with cerebellar predominant MSA (MSA-C) were identified. Increased
      level of PiB retention was noted in all patients diagnosed with DLB, but was
      absent in MSA. In those with DLB, glucose hypometabolism corresponded with
      regions of amyloid presence, and included prefrontal, parietotemporal, occipital
      and primary visual cortex regions. MSA patients were distinguished by cerebellar
      glucose hypometabolism. CONCLUSIONS: These findings emphasize the distinguishing
      characteristics between the alpha-synuclein related disorders of DLB and MSA. The
      absence of amyloid in the cases of MSA is a possible distinguishing
      characteristic of the disorder.

PMID- 21195653
TI  - Task-specific dystonia of the lower limb in a flamenco dancer.

PMID- 21195654
TI  - Performing health in place: the holy well as a therapeutic assemblage.
AB  - This paper examines the holy well as a representative therapeutic landscape with
      a particular focus on linking a traditional setting with contemporary theory
      associated with the 'performative turn'. This is developed within the paper to
      suggest a new theoretical model of the 'therapeutic assemblage' containing
      material, metaphoric and inhabited dimensions. Drawing empirical evidence from
      Irish holy wells, complex holistic performances of health are identified within
      such settings. Deeper associations with more-than-representational theory suggest
      new directions in the study of therapeutic landscapes to uncover the importance
      of cultural practice and lay narratives of healing in the creation of healthy
      place.

PMID- 21195655
TI  - A comparison of spatial and social clustering of cholera in Matlab, Bangladesh.
AB  - Infectious diseases often cluster spatially, but can also cluster socially
      because they are transmitted within social networks. This study compares spatial
      and social clustering of cholera in rural Bangladesh. Data include a spatially
      referenced longitudinal demographic database, which consists of approximately
      200,000 people and laboratory-confirmed cholera cases from 1983 to 2003. Matrices
      are created of kinship ties between households using a complete network design
      and distance matrices are also created to model spatial relationships. Moran's I
      statistics are calculated to measure clustering within both social and spatial
      matrices. The results show that cholera always clusters in space and seldom
      within social networks. Cholera is transmitted mostly through the local
      environment rather than through person-to-person contact. Comparing spatial and
      social network analysis can help improve understanding of disease transmission.

PMID- 21195656
TI  - Reconstruction of a 3D surface from video that is robust to missing data and
      outliers: application to minimally invasive surgery using stereo and mono
      endoscopes.
AB  - Minimally invasive surgery (MIS) offers great benefits to patients compared with
      open surgery. Nevertheless during MIS surgeons often need to contend with a
      narrow field-of-view of the endoscope and obstruction from other surgical
      instruments. He/she may also need to relate the surgical scene to information
      derived from previously acquired 3D medical imaging. We thus present a new
      framework to reconstruct the 3D surface of an internal organ from endoscopic
      images which is robust to measurement noise, missing data and outliers. This can
      provide 3D surface with a wide field-of-view for surgeons, and it can also be
      used for 3D-3D registration of the anatomy to pre-operative CT/MRI data for use
      in image guided interventions. Our proposed method first removes most of the
      outliers using an outlier removal method that is based on the trilinear
      constraints over three images. Then data that are missing from one or more of the
      video images (missing data) and 3D structure are recovered using the structure
      from motion (SFM) technique. Evolutionary agents are applied to improve both the
      efficiency of data recovery and robustness to outliers. Furthermore, an
      incremental bundle adjustment strategy is used to refine the camera parameters
      and 3D structure and produce a more accurate 3D surface. Experimental results
      with synthetic data show that the method is able to reconstruct surfaces in the
      presence of feature tracking errors (up to 5 pixel standard deviation) and a
      large amount of missing data (up to 50%). Experiments on a realistic phantom
      model and in vivo data further demonstrate the good performance of the proposed
      approach in terms of accuracy (1.7 mm residual phantom surface error) and
      robustness (50% missing data rate, and 20% outliers in in vivo experiments).

PMID- 21195657
TI  - Interplay between SIRT proteins and tumour suppressor transcription factors in
      chemotherapeutic resistance of cancer.
AB  - Sirtuins, commonly referred to as SIRTs, are a family of seven mammalian NAD+
      dependent deacetylases implicated in the regulation of critical biological
      processes, including metabolism, cell division, differentiation, survival, and
      senescence. These diverse functions reflect the ability of SIRTs to target and
      modify a broad spectrum of protein substrates, including cytoskeletal proteins,
      signalling components, transcription factors, and histones. SIRTs are also
      implicated in tumorigenesis as well as in the response of the tumour to
      chemotherapy. In particular, SIRT1 has been found to be overexpressed in many
      drug resistant cancers. Emerging evidence suggests that the role of SIRTs in drug
      resistance may be foremost related to their ability to target and modulate the
      activity of tumour suppressors, including p53, p73, E2F1, and FOXO3a. In other
      words, while SIRT-dependent deacetylation of transcription factors is normally
      used to fine-tune gene expression, this function is hijacked by cancer cells to
      evade proliferative arrest and cell death in response to chemotherapy.
      Consequently, interventions predicated on disrupting the interactions between
      tumour suppressors and SIRTs may be effective in circumventing or reversing drug
      resistance in cancer.

PMID- 21195658
TI  - Label-free detection of polynucleotide single-base mismatch via pyrene probe
      excimer emission.
AB  - The pyrene probe and pyrene-labeled oligonucleotides (ODNs) probe are expected to
      be candidates as fluorescent probe for DNA assay. In particular, label-free
      detection is a very hot because of its simpleness, speediness and cheapness.
      Herein, we have investigated the use of a pyrenylakylammonium salt, a novel
      fluorescent probe for the detection of one single nucleotide polymorphism (SNP)
      in double stranded DNA. After S1 nuclease digestion, the pyrene probes bind
      electrostatically to the perfect complement DNA and emit a strong excimer
      emission. However, treatment of the non-complementary DNA with S1 nuclease caused
      nucleotide fragments of less than 5 bases, which could not induce excimer
      emission. By comparing ratio of excimer to monomer fluorescence between normal
      and mutant DNA after S1 nuclease digestion, One-base mutation in DNA was detected
      easily. This new method may be applied to the detection of SNP.

PMID- 21195659
TI  - Quantum mechanical study of the structure and spectroscopic (FT-IR, FT-Raman,
      13C, 1H and UV), first order hyperpolarizabilities, NBO and TD-DFT analysis of
      the 4-methyl-2-cyanobiphenyl.
AB  - The Fourier transform infrared (FT-IR) and FT-Raman of 4-methyl-2-cyanobiphenyl
      (4M2CBP) have been recorded and analyzed. The equilibrium geometry, bonding
      features and harmonic vibrational frequencies have been investigated with the
      help of density functional theory (DFT) method. The assignments of the
      vibrational spectra have been carried out with the help of normal coordinate
      analysis (NCA) following the scaled quantum mechanical force field methodology
      (SQMFF). The 1H and 13C nuclear magnetic resonance (NMR) chemical shifts of the
      molecule were calculated by the Gauge including atomic orbital (GIAO) method. The
      first order hyperpolarizability (beta0) of this novel molecular system and
      related properties (beta, alpha0 and Deltaalpha) of 4M2CBP are calculated using
      HF/6-311G(d,p) method on the finite-field approach. Stability of the molecule
      arising from hyperconjugative interactions, charge delocalization have been
      analyzed using natural bond orbital (NBO) analysis. The results show that charge
      in electron density (ED) in the sigma* and pi* antibonding orbitals and second
      order delocalization energies (E2) confirms the occurrence of intramolecular
      charge transfer (ICT) within the molecule. UV-vis spectrum of the compound was
      recorded and the electronic properties, such as HOMO and LUMO energies, were
      performed by time-dependent density functional theory (TD-DFT) approach. Finally
      the calculations results were applied to simulated infrared and Raman spectra of
      the title compound which show good agreement with observed spectra.

PMID- 21195660
TI  - Development and evaluation of novel one-step TaqMan realtime RT-PCR assays for
      the detection and direct genotyping of genogroup I and II noroviruses.
AB  - BACKGROUND: Current detection and genotyping methods of genogroup (G) I and II
      noroviruses (NoVs) consist of a 2-step approach including detection of viral RNA
      by TaqMan realtime RT-PCR (RT-qPCR) followed by conventional RT-PCR and
      sequencing of partial regions of ORF1 or ORF2. OBJECTIVE: To develop novel long
      template one-step TaqMan assays (L-RT-qPCR) for the rapid detection and direct
      genotyping of GI and GII NoVs and to evaluate the sensitivity and specificity of
      the assays. STUDY DESIGN: GI and GII-specific broadly reactive L-RT-qPCR assays
      were developed by combining existing NoV primers and probes targeting the open
      reading frame (ORF)1-ORF2 junction as well as region C at the 5'-ORF2. The assays
      were validated using GI and GII RNA transcripts and a coded panel of 75 stool
      samples containing NoV strains representing 9 GI genotypes and 12 GII genotypes,
      as well as sapoviruses, astroviruses, polioviruses, and rotaviruses. L-RT-qPCR
      products were typed by sequencing. RESULTS: The novel GI and GII L-RT-qPCR assays
      detected and typed all but one of the NoV positive panel samples. As few as 5-500
      RNA copies could be accurately typed by sequencing of amplicons. CONCLUSIONS: We
      developed novel one-step TaqMan RT-qPCR assays for the sensitive detection and
      direct genotyping of GI and GII NoVs from clinical and environmental matrices.

PMID- 21195661
TI  - Temporal dynamics of face inversion at encoding and retrieval.
AB  - OBJECTIVE: The aim of this study was to characterize the temporal dynamics of
      face encoding and recognition as a function of inversion. METHODS: Event-related
      potentials (ERPs) were recorded while participants performed a recognition task
      in which orientation was manipulated both at study and retrieval. This procedure
      was used to compare the effects of same and different orientation at encoding and
      retrieval on early and later recognition-related components. RESULTS: Changes in
      orientation from encoding to retrieval led to worse recognition performance, as
      compared to unchanged face orientations. Changes in face orientation were also
      associated with longer N170 latencies at retrieval. Later memory related ERP
      components (>300 ms) were affected by inversion and changes in orientation in a
      graded manner: upright faces encoded upright yielded the largest old-new effects,
      followed by inverted faces encoded inverted and finally by faces that differed in
      orientation from encoding to retrieval. CONCLUSIONS: These results suggest that
      the disruption of configural information caused by inversion has different
      effects on memory depending on whether the face is presented at retrieval with
      the same orientation as at encoding. SIGNIFICANCE: These findings show a dynamic
      interplay between perception and memory in which face orientation interacts with
      structural encoding and memory.

PMID- 21195662
TI  - Low-intensity, short-interval theta burst stimulation modulates excitatory but
      not inhibitory motor networks.
AB  - OBJECTIVE: Continuous theta burst stimulation (cTBS) administered at a low
      stimulus intensity can reduce the excitability of short interval intracortical
      inhibitory (SICI) networks without affecting the facilitatory intracortical motor
      networks involved in motor evoked potential (MEP) generation. We sought to
      determine whether low-intensity, facilitatory, short duration cTBS (300 stimuli
      over 20 s; cTBS(300)) could modulate SICI without influencing cortical circuits
      involved in MEP generation. METHODS: MEPs and SICI were assessed at baseline and
      5 min and 20 min following cTBS(300) applied at intensities of 60%, 65% or 70% of
      resting motor threshold (RMT). In addition, the effect of cTBS(300) applied at
      60% RMT on low level SICI (20% test MEP suppression) was examined. RESULTS: Low
      intensity cTBS(300) facilitated MEP amplitude when applied at 70% RMT, and
      inhibited MEP amplitude when applied at 65% RMT. In contrast, none of the
      cTBS(300) protocols had significant effects on moderate or low levels of SICI.
      CONCLUSIONS: The effects of cTBS(300) on MEP generating motor networks are highly
      sensitive to stimulation intensity. Low-intensity cTBS(300) does not have
      isolated, facilitatory effects on SICI networks. SIGNIFICANCE: These results
      further highlight the difficulties of selectively facilitating the inhibitory
      circuits within M1 that are responsible for SICI with currently available rTMS
      paradigms.

PMID- 21195663
TI  - Axonal integrity of corticospinal projections to the upper limbs in patients with
      pure hereditary spastic paraplegia.
AB  - OBJECTIVE: Patients with hereditary spastic paraplegia (HSP) show pathological
      findings when transcranial magnetic stimulation (TMS) is used to test
      corticospinal projections to the lower limbs. However, TMS studies on the
      pathways to the upper limbs revealed inconsistent results. Standard clinical TMS
      procedures are not well suited for testing axonal integrity, which is thought to
      be affected in HSP. More appropriate measures can be achieved by testing
      corticospinal projections with the triple stimulation technique (TST). METHODS:
      TST was used to test axonal integrity of corticospinal projections to the upper
      limbs in 15 patients with pure HSP (13 of whom were tested positive for SPG 4)
      and 15 healthy control subjects. RESULTS: TST measurements revealed normal values
      for corticospinal transmission in all 15 patients with pure HSP, as well as in
      all healthy control subjects. No differences between groups could be found.
      CONCLUSIONS: Axonal integrity of projections to the upper limbs is unimpaired in
      patients with pure HSP. The pathological mechanisms leading to spasticity and
      motor disability seem to be restricted to those fibres of the corticospinal
      pathways projecting to the lower limbs. SIGNIFICANCE: Abnormal corticospinal
      function to the upper limbs seems to be incompatible with pure HSP.

PMID- 21195665
TI  - Linking L1CAM-mediated signaling to NF-kappaB activation.
AB  - The cell adhesion molecule L1 (L1CAM) was originally identified as a neural
      adhesion molecule essential for neurite outgrowth and axon guidance. Many studies
      have now shown that L1CAM is overexpressed in human carcinomas and associated
      with poor prognosis. So far, L1CAM-mediated cellular signaling has been largely
      attributed to an association with growth factor receptors, referred to as L1CAM
      'assisted' signaling. New data demonstrate that L1CAM can signal via two
      additional mechanisms: 'forward' signaling via regulated intramembrane
      proteolysis and 'reverse' signaling via the activation of the transcription
      factor nuclear factor (NF)-kappaB. Taken together, these findings lead to a new
      understanding of L1CAM downstream signaling that is fundamental for the
      development of anti-L1CAM antibody-mediated therapeutics in human tumor cells.

PMID- 21195664
TI  - Intact cag pathogenicity island of Helicobacter pylori without disease
      association in Kolkata, India.
AB  - Several genes including the cagA in the cag pathogenicity island (cag PAI) of
      Helicobacter pylori are thought to be associated with the gastroduodenal diseases
      and hence variation in the genetic structure of the cag PAI might be responsible
      for different clinical outcomes. Our study was undertaken to characterize the cag
      PAI of H. pylori strains from duodenal ulcer (DU) patients and asymptomatic or
      non-ulcer dyspepsia (NUD/AV) subjects from Kolkata, India. Strains isolated from
      52 individuals (30DU and 22NUD/AV) were analyzed by PCR using 83 different
      primers for the entire cag PAI and also by dot-blot hybridization. Unlike H.
      pylori strains isolated from other parts of India, 82.6% of the strains used in
      this study had intact cag PAI, 9.6% had partially deleted cag PAI, and 7.7% of
      the strains lacked the entire cag PAI. Dot-blot hybridization yielded positive
      signals in 100% and 93.8% of PCR-negative strains for HP0522-523 and HP0532
      HP0534 genes, respectively. An intact cagA promoter region was also detected in
      all cagA-positive strains. Furthermore, the expression of cagA mRNA was confirmed
      by RT-PCR for the representative strains from both DU and NUD/AV subjects
      indicating the active cagA promoter regions of these strains. A total of 66.7% of
      Kolkata strains produced a ~390-bp shorter amplicon than the standard strain
      26695 for the HP0527 gene, homologue of virB10. However, sequence analyses
      confirmed that the deletion did not alter the reading frame of the gene, and mRNA
      transcripts were detected by RT-PCR analysis. The strains isolated from DU and
      NUD/AV express CagA protein and possess a functional type IV secretion system, as
      revealed by Western blot analyses. Interestingly, no significant differences in
      cag PAI genetic structure were found between DU and NUD/AV individuals suggesting
      that other bacterial virulence factors, host susceptibility, and environmental
      determinants also influence the disease outcome at least in certain geographical
      locations.

PMID- 21195666
TI  - Biomolecular strategies of bone augmentation in spinal surgery.
AB  - Autologous bone grafts and allografts are the most accepted procedures for
      achieving spinal fusion. Recently, breakthroughs in understanding bone biology
      have led to the development of novel approaches to address the clinical problem
      of bone regeneration in an unfavorable environment, while bypassing the drawbacks
      of traditional treatments, including limited availability, donor site morbidity,
      risk of disease transmission and reduced osteogenicity. These approaches have
      also been studied for their effectiveness in reaching successful spinal fusion.
      This review focuses on the cellular and molecular mechanisms explaining the
      rationale behind these methods, including bone marrow aspirate and mesenchymal
      stem cells, platelet-rich plasma, bone morphogenetic proteins and gene therapy,
      which have opened a promising perspective in the field of bone formation in
      spinal surgery.

PMID- 21195667
TI  - Is history taking a dying skill? An exploration using a simulated learning
      environment.
AB  - History taking is a vital component of patient assessment. Nurses need sound
      interviewing skills to identify care priorities. Verbal and non-verbal cues
      provide triggers to follow-up with appropriate questions during health assessment
      for development of appropriate care plans. This skill, however, is a difficult
      one for students to learn and develop. This paper reports on a study that
      explored the value of video-recording, facilitated review and debriefing
      following a simulated patient experience to enhance final year nursing students'
      history taking and assessment skills. Scenarios, from commonly encountered
      situations, with imbedded cues were developed. Actors were employed as simulated
      patients from whom students took histories while being videotaped. Video
      recordings were then reviewed by each student with a lecturer to highlight missed
      cues or areas where questioning could be developed. These were later analysed to
      explore cue identification. Finally, a focus group was conducted with
      participants to elicit feedback on the experience. Findings suggested that it was
      a valuable exercise. Students lacked prior appreciation for many aspects, such as
      lifestyle, on planning care. Some reported never having had opportunity during
      clinical placement to take a full history. Analysis of recordings identified
      commonly missed social cues and failure to fully explore emerging data.

PMID- 21195668
TI  - Is the fertility treatment itself a risk factor for early pregnancy loss?
AB  - This longitudinal multicentre cohort study aimed to identify the role of the
      conception mode in infertile couples with an early pregnancy loss (EPL). All
      couples referred to the fertility clinic for the first time in the period 2002
      2006 because of infertility were followed up to their first clinical pregnancy
      (n=1809). EPL was the outcome of 286 (15.8%) pregnancies. EPL rates for the
      different conception modes were as follows: spontaneous 14.5% (125/864),
      ovulation induction 15.8% (42/266), intrauterine insemination 25.0% (5/20),
      intrauterine insemination combined with ovarian stimulation 18.2% (37/203), IVF
      16.3% (31/190), intracytoplasmic sperm injection (ICSI) 14.9% (30/202) and frozen
      embryo transfer (FET) 26.2% (16/61). After adjusting for female age, male age,
      hospital, obstetric history, female smoking habit, male alcohol use, menstrual
      cycle type and infertility diagnosis, the EPL rate after FET was significantly
      increased (odds ratio 2.2, 95% CI 1.14-4.19) compared with spontaneous
      conception. Embryo quality was comparable in fresh and frozen embryos. Other
      fertility treatments showed no increased miscarriage rate. Therefore, it is
      concluded that even after adjustment for confounding factors conception through
      FET remained an independent risk factor for EPL. Other modes of conception were
      not related with EPL.

PMID- 21195669
TI  - Effect of the new legislation and single-embryo transfer policy in Turkey on
      assisted reproduction outcomes: preliminary results.
AB  - New legislation concerning assisted reproduction treatments was introduced in
      Turkey in March 2010 in order to reduce the number of multiple pregnancies. This
      new legislation limits the number of embryos to be transferred to one under 35
      years of age in the first or second treatment cycles and to two in the third or
      further cycles or for 35 and older ages. The aim of this multicentre study was to
      investigate the effect of this new law on clinical pregnancy and multiple
      pregnancy rates. Outcomes were compared in equal periods of 2.5 months before and
      after the new law, and further investigation was conducted for two different age
      groups: <35 and >= 35. The clinical pregnancy rates decreased from 39.9 to 34.5%
      and multiple pregnancy rates decreased from 23.1 to 5.3% (P<0.001) for the
      overall population. The outcomes of the <35 age group and >= 35 age group were
      also similar to that of the overall population. These results suggest that under
      the new legislation multiple pregnancy rates are significantly reduced without
      causing a significant decline in the pregnancy rates.

PMID- 21195670
TI  - Local pulmonary immunotherapy with siRNA targeting TGFbeta1 enhances
      antimicrobial capacity in Mycobacterium tuberculosis infected mice.
AB  - In this study we demonstrate that it is possible to shift the immune system
      during a chronic infection with Mycobacterium tuberculosis. TGFbeta and IL10
      cytokines inhibit the Th1 response during chronic pulmonary infection with M.
      tuberculosis. We show that intrapulmonary delivery of siRNA targeting TGFbeta1 is
      able to reduce the pulmonary bacillary load in mice chronically infected with M.
      tuberculosis: an effect that appears to be partly dependent on IL10 expression.
      To demonstrate this, we induced gene silencing of tgfbeta1 in the lungs of wild
      type and IL10 knockout mice using a non-invasive aerosolized intrapulmonary
      delivery of siRNA targeting TGFbeta1. Five days after the last treatment with
      siRNA, the levels of tgfb1 transcripts and TGFbeta1 protein were reduced when
      compared with control groups treated with RNase-free water or non-targeting
      siRNA. Mice treated with siRNA also had increased expression of the antimicrobial
      mediators (NO and iNOS) which effectively reduced the bacterial load by 0.17 and
      0.47 log(10) in C57BL/6 and IL-10 KO mice respectively when compared with their
      respective control mice. More importantly, the bacterial load in siRNA treated IL
      10 KO mice four weeks after the last treatment remained 0.32 log(10) lower than
      in control mice.

PMID- 21195671
TI  - The health care journeys experienced by people with epilepsy in Ireland: what are
      the implications for future service reform and development?
AB  - Opportunities exist to significantly improve the quality and efficiency of
      epilepsy care in Ireland. Historically, epilepsy research has focused on
      quantitative methodologies that often fail to capture the invaluable insight of
      patient experiences as they negotiate their health care needs. Using a
      phenomenological approach, we conducted one-to-one interviews with people with
      epilepsy, reporting on their understanding of their health care journey from
      onset of symptoms through to their first interaction with specialist epilepsy
      services. Following analysis of the data, five major themes emerged: delayed
      access to specialist epilepsy review; uncertainty regarding the competency and
      function of primary care services; significant unmet needs for female patients
      with epilepsy; disorganization of existing epilepsy services; and unmet patient
      information needs. The findings reveal important insights into the challenges
      experienced by people with epilepsy in Ireland and identify the opportunities for
      future service reorganization to improve the quality and efficiency of care
      provided.

PMID- 21195672
TI  - Refractory strictures after Roux-en-Y gastric bypass: operative management.
AB  - BACKGROUND: Stricture of the gastrojejunostomy after Roux-en-Y gastric bypass
      (RYGB) is common in the early postoperative period, with a reported incidence of
      3-27%. Late recalcitrant strictures are much less common. Treatment has varied
      from endoscopic therapy to operative revision of the gastrojejunostomy with or
      without additional anatomic revisions. The origin of the late strictures varies,
      with the most common causes being excessive acid, aspirin, or nonsteroidal anti
      inflammatory drug use, postoperative anastomotic leak, or, as some have
      maintained, smoking. We sought to identify the predictors of gastrojejunostomy
      strictures that require operative management after RYGB and to evaluate the
      clinical outcomes of patients requiring operative revision of the
      gastrojejunostomy stricture after failed nonoperative therapy at an academic
      institution. METHODS: A retrospective review was performed of all patients
      undergoing operative intervention for gastrojejunostomy stricture from 1990 to
      2009 after having undergone RYGB for medically complicated obesity. RESULTS: A
      total of 24 patients required revision of their gastrojejunostomy stricture after
      multiple attempts at nonoperative therapy. The mean interval from RYGB to
      reoperation was 4.3 years (range .5-25). The interval to operative revision for
      anastomotic stricture was substantially less in patients with active anastomotic
      ulcers (n = 6), those who had had a gastrojejunostomy leak after RYGB (n = 5),
      and those with gastrogastric fistulas (n = 7; 20, 23, and 44 months,
      respectively). Of the 24 patients, 23 experienced relief of their symptoms. The
      postoperative morbidity rate was 21%, and the mortality rate was 0%. CONCLUSION:
      Operative revision of strictured gastrojejunostomy is a safe and effective
      procedure for those patients in whom endoscopic therapy has failed. Most
      refractory anastomotic strictures have been secondary to excessive acid (too
      large a proximal pouch), chronic ulceration, or postoperative anastomotic leak.

PMID- 21195673
TI  - Laparoscopic transgastric removal of an eroded gastric band.

PMID- 21195674
TI  - Early use of self-expanding metallic stents to relieve sleeve gastrectomy
      stenosis after intragastric balloon removal.

PMID- 21195675
TI  - Laparoscopic revision of vertical banded gastroplasty to Roux-en-Y gastric
      bypass: outcomes of 105 patients.
AB  - BACKGROUND: Although vertical banded gastroplasty (VBG) was endorsed by the 1991
      National Institutes of Health Consensus Conference for the treatment of morbid
      obesity, it has largely been abandoned owing to the poor long-term weight loss
      and band-related complications. The objective of the present study was to review
      the outcomes of patients who had undergone laparoscopic conversion of VBG to Roux
      en-Y gastric bypass (RYGB) for weight loss or dysphagia and gastroesophageal
      reflux. METHODS: A retrospective review of prospectively collected data from all
      patients who had undergone revision of VBG to RYGB was performed. The data on the
      symptoms, weight loss, co-morbidities, and complications were collected. RESULTS:
      From July 1999 to April 2010, 2397 bariatric procedures were performed. Of these,
      105 (4.4%) were laparoscopic revisions of previous VBG to RYGB. Of the 105
      patients, 103 had undergone open VBG and 2 laparoscopic VBG. Of the 105 patients,
      97 were women and 8 were men. The average patient age was 49 years (range 23-71).
      The median preoperative body mass index was 42 kg/m(2) (range 20-72). Short- and
      long-term complications occurred in 40 patients (38%). No patients died. The
      median length of stay was 2 days. At an average follow-up of 31 months (range 1
      96), the median percentage of excess weight loss was 47% (range -24% to 138%).
      The median decrease in body mass index was 8 kg/m(2) (range -6 to 30). Dysphagia
      had improved or resolved in 100%. Gastroesophageal reflux disease had improved or
      resolved in 95%. Diabetes had improved or went into remission in 90%.
      Hypertension had improved or resolved in 62%. Obstructive sleep apnea had
      improved or resolved in 96%. CONCLUSION: The results of our study have shown that
      laparoscopic revision of VBG to RYGB is a feasible procedure that can provide
      acceptable weight loss and reversal of weight-related co-morbidities.
      Complications were common after revisional bariatric surgery.

PMID- 21195676
TI  - Prevalence of anemia after Roux-en-Y gastric bypass surgery: what is the right
      number?
AB  - BACKGROUND: The reported prevalence of anemia after malabsorptive bariatric
      surgery has varied from 5% to 64% in the post-Roux-en-Y gastric bypass (RYGB)
      population, owing to the small study sample sizes and generally poor follow-up in
      surgical referral practices. The present study estimated the prevalence of anemia
      in the post-RYGB population and determined whether an integrated healthcare
      system with a shared electronic medical record could improve postoperative follow
      up. METHODS: The medical records from 1009 sequential patients who had undergone
      RYGB from 2000 to 2005 were retrospectively analyzed. All anemia data within the
      healthcare system's electronic medical record were accessible. RESULTS: Of the
      1009 medical records, 720 contained >=1 year of follow-up data concerning anemia.
      Anemia had developed or worsened in 259 patients, for a prevalence of 36% in the
      present sample. The anemia was moderate to severe (hemoglobin <10 g/dL) in 88
      patients (12.2%.), many of whom subsequently required parenteral iron. Of the
      1009 patients, the follow-up data for >=3 years concerning anemia were available
      for only 357 patients (35.4%). CONCLUSION: The results of the present study have
      shown that in a large population of patients undergoing RYGB, the prevalence of
      anemia was great enough to justify more intensive long-term screening. We hope
      the findings from the present report influence the national screening standards
      for this patient population.

PMID- 21195677
TI  - Financial implications of coverage for laparoscopic adjustable gastric banding.
AB  - BACKGROUND: Employers and insurers have become increasingly concerned about the
      cost implications of providing coverage for bariatric procedures. We sought to
      quantify the costs and potential cost savings resulting from coverage for
      laparoscopic adjustable gastric banding (LAGB) using a claims analysis. METHODS:
      U.S. healthcare claims data of >7000 LAGB patients and a propensity score-matched
      control group were used to quantify the costs and potential cost savings
      resulting from LAGB for the overall surgery-eligible population and for the
      subset of the surgery-eligible population with diabetes mellitus. The matched
      control group consisted of those with a morbid obesity diagnosis code and/or a
      body mass index >35 kg/m(2) as reported in the Health Risk Assessment data.
      RESULTS: Including the related medical payments in the 90 days before and after
      the procedure, the mean cost of LAGB was approximately $20,000. After placement,
      a modest reduction occurred in the health expenditures relative to the
      preoperative payments. In the postoperative period, these decreases were
      maintained for the LAGB sample. In contrast, the payments for the comparison
      sample continued to increase. As a result, the net cost of coverage for LAGB was
      reduced to 0 by approximately 4 years after band placement. For those with
      diabetes, the net costs resulting from LAGB were reduced to 0 in just >2 years.
      CONCLUSION: These results suggest that the LAGB procedure pays for itself within
      a relatively short period, especially for those with diabetes.

PMID- 21195678
TI  - Short term effect of adaptive servo-ventilation on muscle sympathetic nerve
      activity in patients with heart failure.
AB  - Chronic heart failure (HF) is characterized by sympathetic overactivation and
      periodic breathing. We examined whether adaptive servo-ventilation (ASV) exerts a
      sympathoinhibitory effect in patients with HF via normalizing respiratory
      pattern. Muscle sympathetic nerve activity (MSNA), heart rate, blood pressure,
      respiratory pattern and oxygen saturation were examined in 29 HF patients without
      obstructive sleep apnea (age, 61+/-15years; ejection fraction, 0.32+/-0.09;
      obstructive apnea index, <5/h) before (10 min), during (30 min) and after (10
      min) the application of ASV. Periodic breathing was defined as a repeated
      oscillation of tidal volume with regularly recurring hyperpnea and hypopnea with
      a variation in tidal volume of greater than 25%. The severity of respiratory
      instability was determined using the coefficient of variation of tidal volume (CV
      TV). Of 29 patients with HF, 11 had periodic breathing and 18 did not. There was
      a modest positive correlation between MSNA and CV-TV (n=29, p<0.05). ASV reduced
      respiratory rate, CV-TV and MSNA only in the group with periodic breathing
      (p<0.01). Change in MSNA significantly correlated with changes in respiratory
      rate, CV-TV and presence of periodic breathing. However, multivariate analyses
      revealed that respiratory rate and CV-TV were independent predictors of change in
      MSNA. ASV reduces MSNA by slowing respiratory rates and stabilizing respiratory
      patterns in patients with HF.

PMID- 21195679
TI  - Purification of hemoglobin from red blood cells using tangential flow filtration
      and immobilized metal ion affinity chromatography.
AB  - Two methods for purifying hemoglobin (Hb) from red blood cells (RBCs) are
      compared. In the first method, red blood cell lysate is clarified with a 50 nm
      tangential flow filter and hemoglobin is purified using immobilized metal ion
      affinity chromatography (IMAC). In the second method, RBC lysate is processed
      with 50 nm, 500 kDa, and 50-100 kDa tangential flow filters, then hemoglobin is
      purified with IMAC. Our results show that the hemoglobins from both processes
      produce identical Hb products that are ultrapure and retain their biophysical
      properties (except for chicken hemoglobin, which shows erratic oxygen binding
      behavior after purification). Therefore, the most efficient method for Hb
      purification appears to be clarification with a 50 nm tangential flow filter,
      followed by purification with IMAC, and sample concentration/polishing on a 10-50
      kDa tangential flow filter.

PMID- 21195680
TI  - Development of a liquid chromatography-tandem mass spectrometry with pressurized
      liquid extraction for determination of glucocorticoid residues in edible tissues.
AB  - A multi-residues method using pressurized liquid extraction (PLE) and liquid
      chromatography combined with mass spectrometry (LC-MS/MS) has been developed for
      determination of eight glucocorticoids (prednisone, prednisolone, hydrocortisone,
      methylprednisolone, dexamethasone, betamethasone, beclomethasone,
      fludrocortisone) in muscle of swine, cattle, and sheep. Parameters affecting PLE
      extraction including extraction solvent, extraction temperature, extraction
      pressure and extraction cycles were optimized. The optimized method employed 11
      ml extraction cells, hexane-ethyl acetate (50:50, v/v) as extraction solvent,
      1500 psi of extraction pressure and 50 degrees C of extraction temperature. The
      samples were detected by LC-ESI-MS/MS in negative mode with selected reaction
      monitoring (SRM) mode. The recovery of glucocorticoids spiked at levels of 0.5-6
      MUg kg(-1) ranged from 70.1% to 103.1%; the between-day relative standard
      deviations were no more than 9.6%. The limits of quantification were 0.5-2 MUg
      kg(-1) in muscle. The results demonstrated that the method is simple, fast,
      robust, and suitable for identification and quantification of glucocorticoids
      residues in foods of animal origin.

PMID- 21195681
TI  - Free amino acid quantification by LC-MS/MS using derivatization generated isotope
      labelled standards.
AB  - The further development of derivatizing reagents for plasma amino acid
      quantification by tandem mass spectrometry is described. The succinimide ester of
      4-methylpiperazineacetic acid (MPAS), the iTRAQ reagent, was systematically
      modified to improve tandem mass spectrometer (MS/MS) product ion intensity. 4
      Methylpiperazinebutyryl succinimide (MPBS) and dimethylaminobutyryl succinimide
      (DMABS) afforded one to two orders of magnitude greater MS/MS product ion signal
      intensity than the MPAS derivative for simple amino acids. CD(3) analogues of the
      modified derivatizing reagents were evaluated for preparation of amino acid
      isotope-labelled quantifying standards. Acceptable accuracy and precision was
      obtained with d(3)-DMABS as the amino acid standards derivatizing reagent. The
      product ion spectra of the DMABS amino acid derivatives are diagnostic for
      structural isomers including valine/norvaline, alanine/sarcosine and
      leucine/isoleucine. Improved analytical sensitivity and specificity afforded by
      these derivatives may help to establish liquid chromatography tandem mass
      spectrometry (LC-MS/MS) with derivatization generated isotope-labelled standards
      a viable alternative to amino acids analysers.

PMID- 21195682
TI  - [Non-functioning gangliocytoma of the pituitary gland].

PMID- 21195683
TI  - Centile values for anthropometric variables in Colombian adolescents.
AB  - BACKGROUND AND OBJECTIVE: Reference data for anthropometric parameters are not
      available for adolescents in Cali (Colombia). This study aimed to develop
      representative age- and sex-specific percentiles for anthropometric indicators
      [fat percentage, body mass index (BMI), and waist circumference] in urban
      adolescents aged 10-16 years in Cali. METHODS: The sample (n=1,773) consisted of
      865 boys and 908 girls from the descriptive, cross-sectional population-based
      IFRECNTEC study (Identification of Risk Factors for Non-communicable Chronic
      Diseases in Adulthood in a Population aged 6 to 18 years old attending School in
      the Municipality of Cali, Colombia). Data on anthropometric variables were
      recorded. Smoothed age- and sex- specific 5(th), 25(th), 50(th), 75(th), 90(th)
      and 95(th) centiles were derived using the least mean squares (LMS) regression
      method. RESULTS: In most ages, anthropometric indicators were higher for girls
      than for boys. The BMI p50 ranged from 16.8 to 19.9kg/m2 in boys and from 16.7 to
      21.1kg/m2 in girls. Fat percentage in boys in the p50 varied from ~12% at the
      ages of 10 and 11 years to ~13% at the age of 16 years; for girls, these
      percentages varied from ~13% in the earliest ages to ~16% in older ages. Waist
      circumference was lower in girls than in boys in most ages. CONCLUSION: The
      results of this study could be used to identify adolescents with an elevated risk
      of developing obesity, dyslipidemia, hypertension and cardiovascular disorders in
      adulthood, to plan and implement preventive policies, and to study temporal
      trends. The introduction of centile values will help to classify adolescents from
      Cali and compare their anthropometric indicators with those of a reference
      population.

PMID- 21195684
TI  - Serum free triiodothyronine (T3) to free thyroxine (T4) ratio in treated central
      hypothyroidism compared with primary hypothyroidism and euthyroidism.
AB  - The standard treatment of hypothyroidism (central and primary) consists of
      thyroxine (T4) administration alone. However, the normal thyroid gland produces a
      small proportion of triiodothyronine (T3) directly into the circulation. AIM: We
      aimed to study the free T3 to free T4 ratio in treated central hypothyroidism
      compared with euthyroidism and treated primary hypothyroidism. METHODS: Eighty
      three subjects were included in this cross-sectional study: 36 with central
      hypothyroidism, 20 with primary hypothyroidism and 27 healthy controls. A
      clinical history and a physical examination, including height and weight
      measurement, were performed and body mass index (BMI) was calculated. Fasting
      blood was drawn to measure T3, T4, free T3, free T4 and TSH. RESULTS: The free T3
      to free T4 ratio was lower in treated central hypothyroidism than in euthyroidism
      but was similar to treated primary hypothyroidism. Free T4 was higher in treated
      central and primary hypothyroidism than in euthyroidism. Age, sex and BMI did not
      affect the free T3 to free T4 ratio. CONCLUSIONS: Treated patients with central
      hypothyroidism had a lower free T3 to free T4 ratio, similar free T3 levels and
      higher free T4 concentrations than euthyroid controls, whereas all these
      parameters were similar in central and primary hypothyroid patients treated with
      T4. The question of whether these findings translate into adequate tissue
      concentrations of free thyroid hormones in all tissues remains to be answered.
      Further studies should aim to determine whether clinical outcomes could be
      improved by a treatment achieving more physiological plasma concentrations.

PMID- 21195685
TI  - Tumour necrosis factor-alpha expression in segmental colitis associated with
      diverticulosis is related to the severity of the endoscopic damage.
AB  - BACKGROUND: Tumour necrosis factor-alpha expression may be increased in segmental
      colitis associated with diverticulosis. AIMS: To assess tumour necrosis factor
      alpha expression in segmental colitis associated with diverticulosis in relation
      with the severity of the endoscopic damage. METHODS: 21 patients affected by
      segmental colitis associated with diverticulosis were studied (15 M, 6 F, mean
      age 58.87 years, range 43-85 years). Segmental colitis associated with
      diverticulosis was graduated as mild-moderate (patterns A and C) and severe
      (patterns B and D). Ten patients with moderate-to-severe ulcerative colitis, 10
      patients with moderate-to-severe Crohn's disease, and 10 patients with irritable
      bowel syndrome served as control groups. RESULTS: Tumour necrosis factor-alpha
      expression was significantly higher in segmental colitis associated with
      diverticulosis B (42.7%) and segmental colitis associated with diverticulosis D
      (40%) than in segmental colitis associated with diverticulosis A (19.1%) and
      segmental colitis associated with diverticulosis C (21.1%).Tumour necrosis factor
      alpha expression was lower in segmental colitis associated with diverticulosis A
      and C than in ulcerative colitis and Crohn's disease, whilst no different tumour
      necrosis factor-alpha expression was found between segmental colitis associated
      with diverticulosis B and D and both ulcerative colitis and Crohn's
      disease.Finally, tumour necrosis factor-alpha expression was significantly lower
      in irritable bowel syndrome (8%+/-4) than in every type of segmental colitis
      associated with diverticulosis. CONCLUSIONS: Tumour necrosis factor-alpha
      expression in segmental colitis associated with diverticulosis seems to be
      related to the severity of the endoscopic damage. This behaviour, similar to that
      of the inflammatory bowel diseases (IBD), confirms that this disease should be
      considered as a subtype of IBD.

PMID- 21195686
TI  - [Clinical characteristics of patients with infection due to Influenza A (H1N1)
      2009 and critical pathology].
AB  - OBJECTIVE: Retrospective, observational study in children hospitalized due to
      Influenza A (H1N1) between October 2009 and February 2010, emphasizing on those
      who required intensive therapy. MATERIAL AND METHODS: Risk factors, symptoms,
      course, complications, mortality, time of disappearance of RT-PCR Influenza A
      (H1N1), average length of stay and duration of treatment with oseltamivir, were
      studied, comparing critically ill patients (group I) with the rest of
      hospitalized patients (group II). RESULTS: A total of 38 children, with a mean
      age of 5.03+/-4.6 years were admitted during the study period. Six patients
      required intensive care, 83.3% had risk factors for influenza A (H1N1) compared
      with 62.5% in group II. Fever > 38 degrees C was the predominant symptom (92.1%).
      Respiratory symptoms were significantly more frequent in group I (83.3% vs. 33.6;
      P<.01). Two critically ill patients required mechanical ventilation due to ARDS
      (acute respiratory distress syndrome). One patient with exacerbation of chronic
      respiratory failure responded favourably to high-flow oxygen. One patient
      developed fulminant myocarditis and required ECMO (Extracorporeal Membrane
      Oxygenation) because of secondary cardiogenic shock, which developed into
      multiple organ dysfunction and brain death. Oseltamivir therapy was given for an
      average of 8.6 days in group I and 4.5 days in group II (P<.05), checking the
      negativity of RT-PCR Influenza A (H1N1) in 7+/-2 days. The average stay was
      significantly higher in group I. Two patients admitted to PICU died. CONCLUSIONS:
      The presence of risk factors increases the likelihood of unfavourable outcome:
      high mortality among patients requiring intensive care. Monitoring of RT-PCR
      Influenza A (H1N1) could help establish the duration of isolation measures.

PMID- 21195687
TI  - Application of enhanced stromal vascular fraction and fat grafting mixed with PRP
      in post-traumatic lower extremity ulcers.
AB  - BACKGROUND: The authors presented their experience in regenerative surgery of
      post-traumatic lower extremity ulcers, evaluating the effects related to the use
      of Enhanced Stromal Vascular Fraction (e-SVF) and Fat Grafting with Platelet rich
      Plasma (PRP). The authors compared the results of two control groups. METHOD: The
      analysis involved 20 patients aged between 23 to 62 years affected by post
      traumatic lower extremity ulcers. 10 patients managed with e-SVF and 10 patients
      managed with Fat grafting+PRP in the Plastic and Reconstructive Surgery
      Department at "Tor Vergata" University Rome. Patients in the first control group
      (n=10), were treated only with curettage and application of hyaluronic acid in
      the bed of ulcers. Patients in the second control group (n=10), were treated only
      with PRP. RESULTS: The authors showed that wounds treated with e-SVF healed
      better than those treated with hyaluronic acid. In fact, after 9.7 weeks,
      patients treated with e-SVF underwent 97.9% +/- 1.5% reepithelialisation compared
      to 87.8% +/- 4.4% of the first control group (only hyaluronic acid; p<0.05).
      Patients treated with PRP and fat grafting also showed an improvement in
      reepithelialisation; in fact after 9.7 weeks, they underwent a 97.8% +/- 1.5%
      reepithelialisation compared to 89.1% +/- 3.8% of the second control group (only
      PRP; p<0.05). As reported e-SVF and PRP mixed with fat grafting were the two
      treatments evidencing improvement in the healing of patients post-traumatic
      extremity ulcers. CONCLUSIONS: The results obtained proved the efficacy of these
      treatments, and the satisfaction of the patients confirmed the quality of the
      results.

PMID- 21195688
TI  - Characterization of an electric stimulation protocol for muscular exercise.
AB  - OBJECTIVE: The aim of this study is to evaluate the effect of rest time (ten
      minutes) on muscular strength production during a training session under
      electrical stimulation. PATIENTS AND METHODS: The isometric force output of the
      quadriceps femoris muscle was recorded during four sessions of stimulation of
      five minutes (15 maximal contractions: five seconds on and 15 seconds of rest),
      on 13 healthy adults. These four sessions are spaced out of ten minutes of
      recovery. The frequency of current is 100 Hz. RESULTS: At the 60th contraction,
      muscular force reaches 53 +/- 7% of MVC. This value is significantly more
      important comparatively with a training session without rest time inside (27 +/-
      6% of MVC). CONCLUSION: The efficiency of electrical stimulation to improve
      muscle strength seems to be dependent on number of contractions per session with
      a high level of force production (> =60% de MVC). The protocol including
      intermediate periods of recovery seems more effective in order to produce a high
      level of force during all the training session.

PMID- 21195689
TI  - Clear-cell renal carcinoma metastasis to the base of the tongue and sphenoid
      sinus: Two very rare atypical ENT locations.
AB  - INTRODUCTION: Kidney cancer, and especially clear cell carcinoma, has an
      unpredictable clinical course, with metastatic potential that is variable over
      time and in location. Six percent of atypical locations are ENT. The three most
      frequent sites are the thyroid, sinus and parotid gland. CASE REPORT: We report
      two rare locations: the base of the tongue, and the sphenoid sinus. DISCUSSION:
      First-line treatment is surgical, due to low radiosensitivity, with radiation
      therapy as a possible second line. Functional impact is a prime issue, to avoid
      functional mutilation. CONCLUSION: Such metastases may sometimes occur years
      after the discovery of the primitive renal tumor; any history of kidney cancer
      should, therefore, be noted in patients with suspect ENT lesions.

PMID- 21195690
TI  - Membrane interaction of segment H1 (NS4B(H1)) from hepatitis C virus non
      structural protein 4B.
AB  - NS4B protein from hepatitis C virus (HCV) is a highly hydrophobic protein
      inducing a rearrangement of endoplasmic reticulum membranes responsible of the
      HCV replication process. Different helical elements have been found in the N- and
      C- terminal domains of the protein, which seem to be responsible for many key
      aspects of the viral replication process. In this work we have carried out a
      study of the binding and interaction with model biomembranes of peptide NS4B(H1),
      patterned after segment H1, one of these C-terminal previously identified
      segments. We show that NS4B(H1) partitions into phospholipid membranes; its
      membrane activity is modulated by lipid composition, interacting preferentially
      with negatively charged phospholipids as well as with sphingomyelin. Furthermore,
      the change in its sequence prevents the resulting peptide from interacting with
      the membrane. These data would support its role in the interaction of NS4B with
      the membrane and suggest that the region where this peptide resides could be
      involved in the membrane alteration which must occur in the HCV replication
      and/or assembly process.

PMID- 21195691
TI  - Induction of IFN-gamma by a highly branched 1,3-beta-d-glucan from Aureobasidium
      pullulans in mouse-derived splenocytes via dectin-1-independent pathways.
AB  - We have previously elucidated the precise structure of a unique type of 1,3-beta
      D-glucan, AP-FBG (Aureobasidium pullulans-fermented beta-D-glucan), from the
      fungus A. pullulans and found that AP-FBG strongly induced the production of
      various cytokines in DBA/2 mouse-derived splenocytes in vitro. However, the
      mechanism(s) of action of AP-FBG on in vitro mouse primary cells have not been
      characterized in detail. Herein, we report that the production of IFN-gamma in
      DBA/2 mouse-derived splenocytes by AP-FBG was not inhibited following treatment
      with an anti-dectin-1 neutralizing antibody. In addition, AP-FBG not only failed
      to activate dectin-1-mediated signaling pathways, examined by a reporter gene
      assay but also failed to bind to dectin-1, a pivotal receptor for 1,3-beta-D
      glucan. Taken together, AP-FBG induced cell activation via dectin-1-independent
      pathways.

PMID- 21195692
TI  - A novel 3' splice-site mutation and a novel gross deletion in leukocyte adhesion
      deficiency (LAD)-1.
AB  - A patient was diagnosed with leukocyte adhesion deficiency-1. She was born in
      1996 and her parents are not known to be related. Her leukocytes expressed less
      than 2% of the CD18 antigens relative to normal individuals. Molecular analysis
      revealed that she is a compound heterozygote. She inherited a 27,703bp deletion
      from her father (g.43201_PTTG1IP:10890del27703), spanning from intron 11 of the
      gene for the beta2 integrin (ITGB2, CD18, NG_007270.2) to intron 2 of the gene
      for the Pituitary Tumor-Transforming Gene 1 Interacting Protein (PTTG1IP,
      NC_000021.8). The maternal allele has a g.23457C>A mutation at position -10 in
      intron 2 of the ITGB2 gene, resulting in the activation of a cryptic 3' splice
      site in intron 2 to include 43 intronic nucleotides (r.[59-43_59-1ins;59-10C>A]).

PMID- 21195693
TI  - Characterization of interactions between LPS transport proteins of the Lpt
      system.
AB  - The lipopolysaccharide transport system (Lpt) in Gram-negative bacteria is
      responsible for transporting lipopolysaccharide (LPS) from the cytoplasmic
      surface of the inner membrane, where it is assembled, across the inner membrane,
      periplasm and outer membrane, to the surface where it is then inserted in the
      outer leaflet of the asymmetric lipid bilayer. The Lpt system consists of seven
      known LPS transport proteins (LptA-G) spanning from the cytoplasm to the cell
      surface. We have shown that the periplasmic component, LptA is able to form a
      stable complex with the inner membrane anchored LptC but does not interact with
      the outer membrane anchored LptE. This suggests that the LptC component of the
      LptBFGC complex may act as a dock for LptA, allowing it to bind LPS after it has
      been assembled at the inner membrane. That no interaction between LptA and LptE
      has been observed supports the theory that LptA binds LptD in the LptDE
      homodimeric complex at the outer membrane.

PMID- 21195694
TI  - DNA replication defects in a mutant deficient in the thioredoxin homolog YbbN.
AB  - Escherichia coli contains two thioredoxins, Trx1 and Trx2, and a thioredoxin-like
      protein, YbbN, that displays both redox and chaperone properties. Since three out
      of the six proteins of the YbbN interactome (Butland et al., 2005) are components
      of DNA polymerase 3 holoenzyme (i.e. the beta-clamp DnaN, the theta subunit HolE
      and the delta' subunit HolB), we investigated whether the ybbN mutant presents
      DNA replication defects. We found that this mutant incorporates (3)H-thymidine at
      higher rates than the parental strain and displays overinitiation, hypermutator
      and filamentation phenotypes with the occurrence of anucleated cells. Moreover,
      YbbN functions as a bona fide chaperone in the refolding of the urea-unfolded
      beta-clamp. These results suggest that the DNA replication and cell division
      defects of the ybbN mutant might best be explained by chaperone functions of YbbN
      in the biogenesis of DNA polymerase 3 holoenzyme.

PMID- 21195695
TI  - NO signaling in exercise training-induced anti-apoptotic effects in human
      neutrophils.
AB  - Short-lived neutrophils play a predominant role in innate immunity, the effects
      of exercise training on neutrophil survival is unclear. In this study, we
      investigated the underlying mechanisms of training effects on human neutrophil
      apoptosis. Healthy male subjects were trained on a cycling ergometer for 8 weeks
      and followed by 4 weeks of detraining. Blood neutrophils were collected before
      exercise, after training, and after detraining. Comparing with pre-exercise
      specimens, neutrophils collected after training showed reduced apoptosis rate,
      which partially returned after detraining. Various intracellular proteins,
      including iNOS, Mcl-1, A1, Grp78, and IL-8, were upregulated by training, and
      they remained high after detraining. Upregulated iNOS was closely correlated with
      these anti-apoptotic molecules in neutrophils. Furthermore, the possible
      mechanism by which iNOS suppressed apoptosis was explored. Neutrophil apoptosis
      was accelerated by blocking and retarded by stimulating the endogenous iNOS
      activity. As an anti-apoptosis mediator of NO signaling, the Mcl-1 level dropped
      by depletion of the major NO downstream molecule cGMP and such loss of Mcl-1 was
      avoidable when supplying exogenous NO. Upon activation of NO-cGMP signaling,
      neutrophils held increased Mcl-1 expression and delayed apoptosis. Collectively,
      our results suggested that exercise training may retard neutrophil apoptosis by
      upregulating the iNOS-NO-cGMP-Mcl-1 pathway.

PMID- 21195697
TI  - The effects of catechol-O-methyl-transferase polymorphism Val158Met on functional
      connectivity in healthy young females: a resting EEG study.
AB  - The catechol-O-methyl-transferase (COMT) gene has been linked to a wide spectrum
      of human phenotypes, including cognition, affective response, pain sensitivity,
      anxiety and psychosis. This study examined the modulatory effects of COMT
      Val158Met on neural interactions, indicated by connectivity strengths. Blood
      samples and resting state eyes-closed EEG signals were collected in 254 healthy
      young females. The COMT Val158Met polymorphism was decoded into 3 groups:
      Val/Val, Val/Met and Met/Met. The values of mutual information of 20 frontal
      related channel pairs across delta, theta, alpha and beta frequencies were
      analyzed based on the time-frequency mutual information method. Our one-way ANOVA
      analyses revealed that the significant connection-frequency pairs were relatively
      left lateralized (P<0.01) and included F7-T3 and F7-C3 at delta frequency, and F3
      F4, F7-T3, F7-C3, F7-P3, F3-C3, F3-F7 and F4-F8 at theta frequency. The F-test at
      F7-T3 and F7-C3 theta surpassed the statistical threshold of P<0.003 (after
      Bonferroni correction). For all the above connection-frequency pairs, there was a
      dose-dependent trend in the connectivity strengths of the alleles as follows:
      Val/Val>Val/Met>Met/Met. Our analyses complemented previous literature regarding
      neural modulation by the COMT Val158Met polymorphism. The implication to the
      pathogenesis in schizophrenia was also discussed. Further studies are needed to
      clarify whether there is gender difference on this gene-brain interaction.

PMID- 21195696
TI  - Beneficial effects of hydrogen gas against spinal cord ischemia-reperfusion
      injury in rabbits.
AB  - Recently, hydrogen gas (H2) is reported to be a new therapeutic agent in organ
      damage induced by ischemia-reperfusion (I/R). The present study was designed to
      investigate the beneficial effects of H2 against spinal cord I/R injury and its
      associated mechanisms. Spinal cord ischemia was induced by infrarenal aortic
      occlusion for 20 min in male New Zealand white rabbits. Treatment with 1%, 2% or
      4% H2 inhalation was given from 10 min before reperfusion to 60 min after
      reperfusion (total 70 min). Here, we found that I/R-challenged animals showed
      significant spinal cord damage characterized by the decreased numbers of normal
      motor neurons and hind-limb motor dysfunction, which was significantly improved
      by 2% and 4 % H2 treatment. Furthermore, we found that the beneficial effects of
      H2 treatment against spinal cord I/R injury were associated with the decreased
      levels of oxidative products [8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) and
      malondialdehyde (MDA)] and pro-inflammatory cytokines [tumor necrosis factor
      alpha (TNF-alpha) and high-mobility group box 1 (HMGB1)], as well as increased
      activities of antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)]
      in serum and spinal cord. In addition, H2 treatment reduced motor neuron
      apoptosis in the spinal cord of this model. Thus, H2 inhalation may be an
      effective therapeutic strategy for spinal cord I/R damage.

PMID- 21195698
TI  - Association study of calcitonin gene-related polypeptide-alpha (CALCA) gene
      polymorphism with migraine.
AB  - Migraine is a neurological disorder that is associated with increased levels of
      calcitonin gene-related peptide (CGRP) in plasma. CGRP, being one of the
      mediators of neurogenic inflammation and a phenomenon implicated in the
      pathogenesis of migraine headache, is thus suggested to have an important role in
      migraine pathophysiology. Polymorphisms of the CALCA gene have been linked to
      Parkinson's disease, ovarian cancer and essential hypertension, suggesting a
      functional role for these polymorphisms. Given the strong evidence linking CGRP
      and migraine, it is hypothesised that polymorphisms in the CALCA gene may play a
      role in migraine pathogenesis. Seemingly non functional intronic polymorphisms
      are capable of disrupting normal RNA processing or introducing a splice site in
      the transcript. A 16bp deletion in the first intron of the CALCA gene has been
      reported to be a good match for the binding site for a transcription factor
      expressed strongly in neural crest derived cells, AP-2. This deletion also
      eliminates an intron splicing enhancer (ISE) that may potentially cause exon
      skipping. This study investigated the role of the 16bp intronic deletion in the
      CALCA gene in migraineurs and matched control individuals. Six hundred
      individuals were genotyped for the deletion by polymerase chain reaction followed
      by fragment analysis on the 3130 Genetic Analyser. The results of this study
      showed no significant association between the intronic 16bp deletion in the CALCA
      gene and migraine in the tested Australian Caucasian population. However, given
      the evidence linking CGRP and migraine, further investigation of variants with
      this gene may be warranted.

PMID- 21195699
TI  - The sodium-driven chloride/bicarbonate exchanger NDCBE in rat brain is
      upregulated by chronic metabolic acidosis.
AB  - Acid extruders in neurons prohibit intracellular pH from falling very far below
      normal. Our recent report suggests that the acid-extruding sodium/bicarbonate
      transporter NBCn1 (Slc4a7) in rat brain is upregulated by chronic metabolic
      acidosis. In this study, we examined whether the Na(+)-driven Cl/HCO(3) exchanger
      NDCBE (Slc4a8) is also upregulated by similar systemic acid loads. Immunoblot
      revealed NDCBE protein (130 kDa) expressed in a variety of rat brain regions. In
      the hippocampus, NDCBE was localized to CA1-CA4 pyramidal neurons and dentate
      gyrus granular neurons determined by immunoperoxidase immunohistochemistry. The
      staining was dispersed in cell bodies and dendrites. NDCBE protein expression was
      then compared between rats in chronic metabolic acidosis and control rats.
      Immunoblot of crude plasma membrane fractions from the hippocampus showed a
      slight increase in NDCBE in acidotic rats (p=0.05). However, the expression in
      CA3 pyramidal neurons was significantly increased, determined by
      immunohistochemistry and quantitative analysis. The increase was also observed in
      other neurons including entorhinal cortical neurons, posterior cortical neurons,
      and outer stellate cells in cerebellum. The staining in choroid plexus epithelia
      was unaffected by chronic metabolic acidosis. These data demonstrate that the
      Na(+)-driven Cl/HCO(3) exchanger NDCBE is upregulated by chronic acid loads in a
      cell-specific manner.

PMID- 21195700
TI  - Increased total cytokeratin-18 serum and urine levels in chronic kidney disease.
AB  - BACKGROUND: Increased cell death in chronic kidney disease (CKD) by either
      necrosis or apoptosis has been confirmed by a variety of studies. Possible
      sources are an inadequate persistent inflammation and ischemia as a consequence
      of CKD or caused by the underlying renal disease. Detection of total or caspase
      cleaved cytokeratin 18 (CK-18) is a novel and elegant method to determine
      necrosis or apoptosis of epithelial cells in the patients' sera and urine.
      METHODS: 120 patients with CKD stages 1 to 5 were included in the study. Twenty
      healthy volunteers served as controls. Total and caspase cleaved CK-18 urine and
      serum concentrations were determined by ELISA. RESULTS: The concentration of
      serum total CK-18 was significantly higher in CKD stages 3-5 as compared to the
      healthy controls. Urinary total CK-18 excretion was increased in patients with
      CKD 5 compared to controls. A significant correlation between urine total CK18
      and urine protein and albumin levels was found. Moreover, ROC curve analysis
      showed the potential of serum and especially urine total CK-18 levels to predict
      various CKD stages. CONCLUSIONS: We provide evidence for increased total CK-18
      serum and urine levels in CKD patients, possibly indicating that epithelial cell
      necrosis is prevalent in CKD.

PMID- 21195701
TI  - Effect of obesity on the association between common variations in the HNF1A gene
      region and C-reactive protein level in Taiwanese.
AB  - BACKGROUND: The level of C-reactive protein (CRP), an inflammatory biomarker that
      predicts future cardiovascular events, is a heritable trait that has been
      associated with variants of CRP and hepatic nuclear factor-1alpha (HNF1A) genes.
      Our aim was to test the statistical association between HNF1A
      genotypes/haplotypes and serum CRP level in Taiwanese. METHODS: A sample
      population of 617 Taiwanese subjects (all Han-Chinese origin) was enrolled. Five
      HNF1A single nucleotide polymorphisms (SNPs) rs1920792, rs1169288, rs7310409,
      rs2464196, rs1169310 were genotyped and analyzed. RESULTS: After adjusting for
      clinical covariates, minor alleles of all the 5 study SNPs were associated with
      decreased CRP level (P=0.0078, P=0.0107, P=0.0006, P=0.0004 and P=0.0003,
      respectively). A common haplotype (TGATA) tagged by the minor alleles of study
      SNPs was associated with significantly decreased CRP level (P=0.0112). Subgroup
      analysis revealed that the association between HNF1A genotypes and CRP level
      occurred only in non-obese subjects. CONCLUSIONS: HNF1A polymorphisms are
      independently associated with CRP level in Taiwanese. Further, HNF1A genotypes
      interact with obesity to set CRP level, revealing that genetic determinants for
      CRP level may be different between obese and non-obese individuals.

PMID- 21195702
TI  - Plasma leptin levels and digital pulse volume in obese patients without metabolic
      syndrome--a pilot study.
AB  - BACKGROUND: The mechanism of obesity leading to endothelial function is complex,
      and involves many adipokines and inflammatory cytokines. The data is especially
      lacking in obese patients without metabolic syndrome. We assessed the
      relationship among endothelial dysfunction, anthropometric indices, adipokines
      and inflammatory cytokines in this population. METHODS: Obese patients without
      metabolic syndrome were included in this study. The plasma resistin, leptin,
      retinol-binding-protein 4 and inflammatory cytokines were examined. Endothelial
      function was assessed by a fingertip peripheral arterial tonometry (PAT) device.
      Data are expressed as the natural logarithm (ln) of the PAT ratio. Endothelial
      dysfunction was defined by a ln (PAT ratio) <0.30. RESULTS: A total of 35
      patients were enrolled, 11 of whom were with endothelial dysfunction. There was a
      significant difference of ln leptin (p=0.007), ln [leptin/visceral fat thickness]
      (p=0.004) and ln [leptin/subcutaneous fat thickness] (p<0.001) between patients
      with and without endothelial dysfunction. Multivariate linear regression analyses
      showed that ln [leptin/subcutaneous fat thickness] was significantly related to
      the ln (PAT ratio) (p=0.002). Using ln [leptin/subcutaneous fat thickness] to
      detect endothelial dysfunction, the area of receiver operating characteristic
      curves was 0.843 (p=0.002). Using 6.10 as a cutoff point, the sensitivity and
      specificity to determine endothelial dysfunction were 91% and 78%, respectively.
      CONCLUSION: Abnormal digital vascular function occurs in obese patients without
      metabolic syndrome. Low plasma leptin/subcutaneous fat ratio is associated with
      endothelial dysfunction in this population.

PMID- 21195703
TI  - A 96-well plate assay for high-throughput analysis of holocarboxylase synthetase
      activity.
AB  - BACKGROUND: Holocarboxylase synthetase (HCS) catalyzes the covalent binding of
      biotin to both carboxylases and histones. Biotinylated carboxylases and
      biotinylated histones play crucial roles in the metabolism of fatty acids, amino
      acids, and glucose, and in gene regulation and genome stability, respectively.
      HCS null mammals are not viable whereas HCS deficiency is linked to developmental
      delays in humans and phenotypes such as short life span and low stress resistance
      in Drosophila. METHODS: HCS-dependent biotinylation of the polypeptide p67 was
      detected and quantified in a 96-well plate format using IRDye-streptavidin and
      infrared spectroscopy. RESULTS: Biotinylation of p67 by recombinant HCS (rHCS)
      and HCS from human cell extracts depended on time, temperature, and substrate
      concentration, all consistent with enzyme catalysis rather than non-enzymatic
      biotinylation. The Michaelis-Menten constant of rHCS for p67 was 4.1+/-1.5
      MUmol/l. The minimal concentration of rHCS that can be detected by this assay is
      less than 1.08 nmol/l. Jurkat cells contained 0.14+/-0.02 U of HCS activity
      [MUmol of biotinylated p67 formed/(nmol/l HCSh)] in 400 MUg of total protein.
      CONCLUSIONS: We developed a 96-well plate assay for high-throughput analysis of
      HCS activity in biological samples and studies of synthetic and naturally
      occurring HCS inhibitors.

PMID- 21195705
TI  - The association of ghrelin polymorphisms with coronary artery disease and
      ischemic chronic heart failure in an elderly Chinese population.
AB  - OBJECTIVE: To investigate the association of coronary artery disease (CAD) and
      ischemic heart failure (IHF) with polymorphisms of the ghrelin gene in elderly
      Chinese patients. DESIGN AND METHODS: Fifty-six patients with ischemic heart
      failure, sixty patients with coronary artery disease without heart failure, and
      one hundred healthy control subjects participated in the study. The polymorphisms
      were evaluated by polymerase chain reaction, sequencing, and fragment length
      polymorphism analysis. RESULTS: Only one single nucleotide polymorphism (SNP),
      Leu72Met (408C/A), was observed across all samples. Gene frequencies of CC and
      allele frequencies of C were significantly greater in the CAD with IHF group than
      those in the CAD without IHF group (p=0.025, p=0.011). There was no significant
      association between the Leu72Met SNP with coronary artery disease risk factors.
      CONCLUSION: Our results suggest that a C allele at position 408 of the ghrelin
      gene is associated with genetic susceptibility to ischemic heart failure in
      Chinese elders.

PMID- 21195704
TI  - Autoantibodies to GP2, the major zymogen granule membrane glycoprotein, are new
      markers in Crohn's disease.
AB  - BACKGROUND: Crohn's disease (CD) is an inflammatory bowel disease (IBD)
      characterized by reactivity against microbial and self antigens. Zymogen granule
      glycoprotein 2 (GP2) was identified as the major autoantigen of CD-specific
      pancreatic autoantibodies (PAB). METHODS: Human GP2 was expressed in the
      Spodoptera frugiperda 9 (Sf9) cell line using the baculovirus system, purified by
      Ni-chelate chromatography, and used as antigen for anti-GP2 IgA and IgG
      assessment by enzyme-linked immunosorbent assays (ELISA). Antibodies to mannan of
      Saccharomyces cerevisiae (ASCA), PAB, and anti-GP2 were investigated in sera of
      178 CD patients, 100 ulcerative colitis (UC) patients, and 162 blood donors (BD).
      RESULTS: Anti-GP2 IgG and IgA were found in 48/72 (66.7%) and 23/72 (31.9%) PAB
      positive and 5/106 (4.7%) and 1/106 (0.9%) PAB negative CD patients (p<0.0001),
      respectively. CD patients displayed significantly higher reactivity to GP2 than
      UC patients and BD (p<0.0001), respectively. Occurrence of anti-GP2 antibodies
      correlated with PAB reactivity (Spearmen's rho=0.493, p<0.00001). There was a
      significant relationship between the occurrence of ASCA IgG and anti-GP2 IgG
      (p=0.0307). CONCLUSIONS: Anti-GP2 IgG and IgA constitute novel CD specific
      autoantibodies, the quantification of which could improve the serological
      diagnosis of IBD.

PMID- 21195706
TI  - Proliferating cells in suborbital tissue drive eye migration in flatfish.
AB  - The left/right asymmetry of adult flatfishes (Pleuronectiformes) is remarkable
      given the external body symmetry of the larval fish. The best-known change is the
      migration of their eyes: one eye migrates from one side to the other. Two extinct
      primitive pleuronectiformes with incomplete orbital migration have again
      attracted public attention to the mechanism of eye migration, a subject of
      speculation and research for over a century. Cranial asymmetry is currently
      believed to be responsible for eye migration. Contrary to that hypothesis, we
      show here that the initial migration of the eye is caused by cell proliferation
      in the suborbital tissue of the blind side and that the twist of frontal bone is
      dependent on eye migration. The inhibition of cell proliferation in the
      suborbital area of the blind side by microinjected colchicine was able to prevent
      eye migration and, thereafter, cranial asymmetry in juvenile Solea senegalensis
      (right sideness, Soleidae), Cynoglossus semilaevis (left sideness,
      Cynoglossidae), and Paralichthys olivaceus (left sideness, Paralichthyidae) with
      a bottom-dwelling lifestyle. Our results correct the current misunderstanding
      that eye migration is driven by the cranial asymmetry and simplify the
      explanation for broken left/right eye-symmetry. Our findings should help to focus
      the search on eye migration-related genes associated with cell proliferation.
      Finally, a novel model is proposed in this research which provides a reasonable
      explanation for differences in the migrating eye between, and sometimes within,
      different species of flatfish and which should aid in our overall understanding
      of eye migration in the ontogenesis and evolution of Pleuronectiformes.

PMID- 21195707
TI  - A regulatory 'landscape effect' over the HoxD cluster.
AB  - Faithful expression of Hox genes in both time and space is essential for proper
      patterning of the primary body axis. Transgenic approaches in vertebrates have
      suggested that this collinear activation process is regulated in a largely gene
      cluster-autonomous manner. In contrast, more recently co-opted expression
      specificities, required in other embryonic structures, depend upon long-range
      enhancer sequences acting from outside the gene clusters. This regulatory
      dichotomy was recently questioned, since gene activation along the trunk seems to
      be partially regulated by signals located outside of the cluster. We investigated
      these alternative regulatory strategies by engineering a large inversion that
      precisely separates the murine HoxD complex from its centromeric neighborhood.
      Mutant animals displayed posterior transformations along with subtle
      deregulations of Hoxd genes, indicating an impact of the centromeric landscape on
      the fine-tuning of Hoxd gene expression. Proximal limbs were also affected,
      suggesting that this 'landscape effect' is generic and impacts upon regulatory
      mechanisms of various qualities and evolutionary origins.

PMID- 21195708
TI  - The metastasis-promoting protein S100A4 regulates mammary branching
      morphogenesis.
AB  - High levels of the S100 calcium binding protein S100A4 also called fibroblast
      specific protein 1 (FSP1) have been established as an inducer of metastasis and
      indicator of poor prognosis in breast cancer. The mechanism by which S100A4 leads
      to increased cancer aggressiveness has yet to be established; moreover, the
      function of this protein in normal mammary gland biology has not been
      investigated. To address the role of S100A4 in normal mammary gland, its spatial
      and temporal expression patterns and possible function in branching morphogenesis
      were investigated. We show that the protein is expressed mainly in cells of the
      stromal compartment of adult humans, and during active ductal development, in
      pregnancy and in involution of mouse mammary gland. In 3D culture models, topical
      addition of S100A4 induced a significant increase in the TGFalpha mediated
      branching phenotype and a concomitant increase in expression of a previously
      identified branching morphogen, metalloproteinase-3 (MMP-3). These events were
      found to be dependent on MEK activation. Downregulation of S100A4 using shRNA
      significantly reduced TGFalpha induced branching and altered E-cadherin
      localization. These findings provide evidence that S100A4 is developmentally
      regulated and that it plays a functional role in mammary gland development, in
      concert with TGFalpha by activating MMP-3, and increasing invasion into the fat
      pad during branching. We suggest that S100A4-mediated effects during branching
      morphogenesis provide a plausible mechanism for how it may function in breast
      cancer progression.

PMID- 21195709
TI  - Reversal effect of Dioscin on multidrug resistance in human hepatoma
      HepG2/adriamycin cells.
AB  - Multidrug resistance is a serious obstacle encountered in cancer treatment. Since
      drug resistance in human cancer is mainly associated with overexpression of the
      multidrug resistance gene 1 (MDR1), the promoter of the human MDR1 gene may be a
      target for multidrug resistance reversion drug screening. In the present study,
      HEK293T cells were transfected with pGL3 reporter plasmids containing the 2kb of
      MDR1 promoter, and the transfected cells were used as models to screen for
      candidate multidrug resistance inhibitors from over 300 purified naturally
      occurring compounds extracted from plants and animals. Dioscin was found to have
      an inhibiting effect on MDR1 promoter activity. The resistant HepG2 cell line
      (HepG2/adriamycin) was used to validate the activity of multidrug resistance
      reversal by Dioscin. Results showed that Dioscin could decrease the resistance
      degree of HepG2/adriamycin cells, and significantly inhibit P-glycoprotein
      expression, as well as increase the accumulation of adriamycin in
      HepG2/adriamycin cells as measured by Flow Cytometric analysis. These results
      suggest that Dioscin is a potent multidrug resistance reversal agent and may be a
      potential adjunctive agent for tumor chemotherapy.

PMID- 21195710
TI  - Melanoma cells produce multiple laminin isoforms and strongly migrate on alpha5
      laminin(s) via several integrin receptors.
AB  - Melanoma cells express and interact with laminins (LMs) and other basement
      membrane components during invasion and metastasis. In the present study we have
      investigated the production and migration-promoting activity of laminin isoforms
      in melanoma. Immunohistochemistry of melanoma specimens and
      immunoprecipitation/western blotting of melanoma cell lines indicated expression
      of laminin-111/121, laminin-211, laminin-411/421, and laminin-511/521. Laminin
      332 was not detected. In functional assays, laminin-111, laminin-332, and laminin
      511, but not laminin-211 and laminin-411, strongly promoted haptotactic cell
      migration either constitutively or following stimulation with insulin-like growth
      factors. Both placenta and recombinant laminin-511 preparations were highly
      active, and the isolated recombinant IVa domain of LMalpha5 also promoted cell
      migration. Function-blocking antibodies in cell migration assays revealed
      alpha6beta1 integrin as the major receptor for laminin-111, and both alpha3beta1
      and alpha6beta1 integrins for laminin-332 and laminin-511. In contrast, isolated
      LMalpha5 IVa domain-promoted melanoma cell migration was largely mediated via
      alphaVbeta3 integrin and inhibited by RGD peptides. Given the ubiquitous
      expression of alpha5 laminins in melanoma cells and in melanoma-target
      tissues/anatomical structures, as well as the strong migration-promoting activity
      of these laminin isoforms, the alpha5 laminins emerge as putative primary
      extracellular matrix mediators of melanoma invasion and metastasis via
      alpha3beta1 and other integrin receptors.

PMID- 21195711
TI  - Reduction of exportin 6 activity leads to actin accumulation via failure of
      RanGTP restoration and NTF2 sequestration in the nuclei of senescent cells.
AB  - We have previously reported that G-actin accumulation in nuclei is a universal
      phenomenon of cellular senescence. By employing primary culture of human diploid
      fibroblast (HDF) and stress-induced premature senescence (SIPS), we explored
      whether the failure of actin export to cytoplasm is responsible for actin
      accumulation in nuclei of senescent cells. Expression of exportin 6 (Exp6) and
      small G-protein, Ran, was significantly reduced in the replicative senescence,
      but not yet in SIPS, whereas nuclear import of actin by cofilin was already
      increased in SIPS. After treatment of young HDF cells with H(2)O(2), rapid
      reduction of nuclear RanGTP was observed along with cytoplasmic increase of
      RanGDP. Furthermore, significantly reduced interaction of Exp6 with RanGTP was
      found by GST-Exp6 pull-down analysis. Failure of RanGTP restoration was
      accompanied with inhibition of ATP synthesis and NTF2 sequestration in the nuclei
      along with accordant change of senescence morphology. Indeed, knockdown of Exp6
      expression significantly increased actin molecule in the nuclei of young HDF
      cells. Therefore, actin accumulation in nuclei of senescent cells is most likely
      due to the failure of RanGTP restoration with ATP deficiency and NTF2
      accumulation in nuclei, which result in the decrease of actin export via Exp6
      inactivation, in addition to actin import by cofilin activation.

PMID- 21195712
TI  - Identification of phospholipids in human meibum by nano-electrospray ionisation
      tandem mass spectrometry.
AB  - Meibum is believed to be the major source of tear film lipids, which are vital in
      the prevention of excess evaporation of the aqueous phase. The complete lipid
      composition of meibum has yet to be established. While earlier studies reported
      the presence of phospholipids in human meibum, recent mass spectrometric studies
      have not detected them. In this study we use electrospray ionisation tandem mass
      spectrometry to investigate the presence of phospholipids in meibum and provide
      comparison to the phospholipid profile of tears. Lipids were extracted from human
      meibum and tear samples using standard biphasic methods and analysed by nano
      electrospray ionisation tandem mass spectrometry using targeted ion scans. A
      total of 35 choline-containing phospholipids were identified in meibum and the
      profile of these was similar to that observed in tears, suggesting tear lipids
      are derived from meibum. The results shown here highlight the need for a
      combination of optimised techniques to enable the identification of the large
      range of lipid classes in meibum.

PMID- 21195713
TI  - Toll-like receptor activation modulates antimicrobial peptide expression by
      ocular surface cells.
AB  - The ability of the ocular surface to respond to pathogens is in part attributed
      to toll-like receptors (TLRs) that recognize conserved motifs on various
      microbes. This study examines TLR expression on various ocular surface cells, if
      TLR agonists can modulate the expression of antimicrobial peptides (AMPs), human
      beta defensins (hBD) and cathelicidin (hCAP-18/LL-37) which maybe functionally
      active against Pseudomonas aeruginosa (PA) and if TLR agonists or AMPs can
      modulate TLR mRNA expression. TLR1-10 mRNA expression was examined in corneal
      epithelial, corneal stromal cells and conjunctival epithelial cells by RT-PCR. To
      confirm protein expression flow cytometry or immunostaining was performed for
      selected TLRs on some cell cultures. Ocular surface cells were cultured with a
      range of TLR agonists and then hBD-1, 2, 3, or hCAP-18 mRNA and protein
      expression was determined by RT-PCR and immunoblotting. In some experiments,
      cells were cultured with a cocktail of agonists for TLR3, 5 and 6/2 and the
      antimicrobial activity of the culture media was tested against PA. TLR mRNA
      expression was also examined in primary human corneal epithelial cells (HCEC)
      treated with either 3 MUg/ml of hBD-2, 5 MUg/ml of LL-37 or TLR4, 5 and 9
      agonists. Overall, the ocular surface cells expressed mRNA for most of the TLRs
      but some differences were found. TLR2 was not detected in corneal fibroblasts,
      TLR4 was not detected in primary cultured or freshly isolated HCEC, TLR5 was not
      detected in conjunctival epithelial cells (IOBA-NHC) and corneal fibroblasts,
      TLR7 was not detected in freshly isolated HCEC and TLR10 was not detected in HCEC
      and IOBA-NHC. TLR8 mRNA was not expressed by any of the samples tested.
      Immunostaining of cadaver corneas revealed TLR5 and 9 expression throughout the
      cornea while TLR3 was significantly expressed only in the epithelium. Flow
      cytometry and immunostaining revealed cultured fibroblasts expressed TLR9 but had
      no significant TLR3 expression. hBD-2 expression was upregulated by TLR1/2, 3, 4,
      5 and 6/2 agonists depending on the cell type, whereas only the TLR3 agonist
      upregulated the expression of hCAP-18 in primary HCEC. The combination of TLR3, 5
      and 6/2 agonists in primary HCEC, upregulated hBD-2 and hCAP-18 mRNA and peptide
      expression and secretion into the culture media, which significantly killed PA.
      This antimicrobial activity was primarily attributed to LL-37. TLR agonists did
      not modulate TLR expression itself, however, LL-37 or hBD-2 downregulated TLR5, 7
      and/or 9 mRNA depending on the cell type. TLRs are expressed on the ocular
      surface and TLR agonists trigger the production of LL-37 and hBD-2, with LL-37
      being particularly important for protecting the ocular surface against PA
      infection.

PMID- 21195714
TI  - Oxytocin in the medial preoptic area facilitates male sexual behavior in the rat.
AB  - Oxytocin (OT) is a versatile neuropeptide that is involved in a variety of
      mammalian behaviors, and its role in reproductive function and behavior has been
      well established. The majority of pharmacological studies of the effects of OT on
      male sexual behavior have focused on the paraventricular nucleus (PVN), ventral
      tegmental area (VTA), hippocampus, and amygdala. Less attention has been given to
      the medial preoptic area (MPOA), a major integrative site for male sexual
      behavior. The present study investigated the effects of intra-MPOA administration
      of OT and (d(CH2)51, Tyr(Me)2, Thr4, Orn8, Tyr-NH29)-vasotocin, an OT antagonist
      (OTA), on copulation in the male rat. The relationship between OT receptor (OTR)
      binding levels in the MPOA and sexual efficiency was also explored.
      Microinjection of OT into the MPOA facilitated copulation in sexually experienced
      male rats, whereas similar injections of an OTA inhibited certain aspects of
      copulation but had no significant effect on locomotor activity in an open field.
      Contrary to expectation, sexually efficient males had lower levels of OTR binding
      in the rostral MPOA compared to inefficient animals. The present data suggest
      that OT activity in the MPOA is not necessary for the expression of male sexual
      behavior but is sufficient to facilitate copulatory behaviors and improve sexual
      efficiency in sexually experienced male rats. These data also suggest that OTR
      activity in the MPOA stimulates anogenital investigation, facilitates the
      initiation of copulation, and plays a role in the sensitization effect of the
      first ejaculation on subsequent ejaculations.

PMID- 21195715
TI  - Fast and efficient characterization of an anti-gliadin monoclonal antibody
      epitope related to celiac disease using resin-bound peptides.
AB  - Celiac disease is a permanent intolerance to gluten. A strong indication for
      celiac disease is the presence of antibodies specific for gliadin, a main
      component of gluten. Using a deamidated immunogenic gliadin fragment,
      corresponding to amino acid residues 58-73 (LQPFPQPQLPYPQPQ) of gliadin a
      monoclonal anti-gliadin antibody has previously been generated. In this study we
      present an alternative approach for fast and efficient epitope mapping of the
      monoclonal anti-gliadin antibody, using gliadin peptide (Lys57)-Glu65-[gliadin 58
      73] as template. This approach involves generation of a number of N-terminally
      truncated peptide analogues in one synthesis, and the use of these resin-bound
      peptides for rapid screening, in order to identify the minimal peptide length
      required for antibody recognition. The peptides were assembled on a TentaGel
      resin equipped with an acid-stable HMBA linker, which allows cleavage of the side
      chain protecting groups but leaves the peptide attached to the resin. If
      required, the peptides may be cleaved from the support under mild basic
      conditions. Using this approach and competitive inhibition assays we identified
      the immunodominant epitope as the PELPYPQPQ sequence, which was located in the C
      terminal end of the gliadin peptide. Our results show that the N-terminal proline
      residue and the C-terminal glutamine residues are essential for antibody
      recognition in addition to the deamidated glutamine residue.

PMID- 21195717
TI  - Models of coalition or alliance formation.
AB  - More than half a century has now elapsed since coalition or alliance formation
      theory (CAFT) was first developed. During that time, researchers have amassed a
      vast amount of detailed and high-quality data on coalitions or alliances among
      primates and other animals. But models have not kept pace, and more relevant
      theory is needed. In particular, even though CAFT is primarily an exercise in
      polyadic game theory, game theorists have devoted relatively little attention to
      questions that motivate field research, and much remains largely unexplored. The
      state of the art is both a challenge and an opportunity. In this review we
      describe a variety of game-theoretic and related modelling approaches that have
      much untapped potential to address the questions that field biologists ask.

PMID- 21195716
TI  - Genetic evidence for a novel interaction between transcriptional activator SoxS
      and region 4 of the sigma(70) subunit of RNA polymerase at class II SoxS
      dependent promoters in Escherichia coli.
AB  - Escherichia coli SoxS activates transcription of the genes of the soxRS regulon,
      which provide the cell's defense against oxidative stress. In response to this
      stress, SoxS is synthesized de novo. Because the DNA binding site of SoxS is
      highly degenerate, SoxS efficiently activates transcription by the mechanism of
      prerecruitment. In prerecruitment, newly synthesized SoxS first forms binary
      complexes with RNA polymerase. These complexes then scan the chromosome for class
      I and II SoxS-dependent promoters, using the specific DNA-recognition properties
      of SoxS and sigma(70) to distinguish SoxS-dependent promoters from the vast
      excess of sequence-equivalent soxboxes that do not reside in promoters.
      Previously, we determined that SoxS interacts with RNA polymerase in two ways: by
      making protein-protein interactions with the DNA-binding determinant of the alpha
      subunit and by interacting with sigma(70) region 4 (sigma(70) R4) both "on-DNA"
      and "off-DNA." Here, we address the question of how SoxS and sigma(70) R4 coexist
      at class II promoters, where the binding site for SoxS either partially or
      completely overlaps the -35 region of the promoter, which is usually bound by
      sigma(70) R4. To do so, we created a tri-alanine scanning library that covers all
      of sigma(70) R4. We determined that interactions between sigma(70) R4 and the DNA
      in the promoter's -35 region are required for activation of class I promoters,
      where the binding site lies upstream of the -35 hexamer, but they are not
      required at class II promoters. In contrast, specific three-amino-acid stretches
      are required for activation of class I (lac) and class II (galP1) cyclic AMP
      receptor protein-dependent promoters. We conclude from these data that SoxS and
      sigma(70) R4 interact with each other in a novel way at class II SoxS-dependent
      promoters such that the two proteins do not accommodate one another in the -35
      region but instead SoxS binding there occludes the binding of sigma(70) R4.

PMID- 21195718
TI  - An integro-partial differential equation for modeling biofluids flow in fractured
      biomaterials.
AB  - A novel mathematical model in the framework of a nonlinear integro-partial
      differential equation governing biofluids flow in fractured biomaterials is
      proposed, solved, verified, and evaluated. A semi-analytical solution is derived
      for the equation, verified by a mass-lumped Galerkin finite element method (FEM),
      and calibrated with two in vitro experimental datasets. The solution process uses
      separation of variables and results in explicit expression involving complete and
      incomplete beta functions. The proposed semi-analytical model shows reasonable
      agreements with the finite element simulator as well as with two in vitro
      experimental time series and can be successfully used to simulate biofluids (e.g.
      water, blood, oil, etc.) flow in natural and synthetic porous biomaterials.

PMID- 21195720
TI  - Synaptoproteomics of learned helpless rats involve energy metabolism and cellular
      remodeling pathways in depressive-like behavior and antidepressant response.
AB  - Although depression is a severe and life-threatening psychiatric illness, its
      pathogenesis still is essentially unknown. Recent studies highlighted the
      influence of environmental stress factors on an individual's genetic
      predisposition to develop mood disorders. In the present study, we employed a
      well-validated stress-induced animal model of depression, Learned Helplessness
      paradigm, in rats. Learned helpless (LH) and non-learned helpless (NLH) rats were
      treated with nortriptyline, a tricyclic antidepressant. The resulting 4 groups
      (LH vs. NLH, treated vs. non-treated), were subjected to global analysis of
      protein expression, a powerful approach to gain insight into the molecular
      mechanisms underlying vulnerability to psychiatric disorders and the long-term
      action of drug treatments. Many of the biological targets of antidepressant drugs
      are localized at synapses. Thus, to reduce the complexity of the proteome
      analyzed and to enrich for less abundant synaptic proteins, purified nerve
      terminals (synaptosomes) from prefrontal/frontal cortex (P/FC) and hippocampus
      (HPC) of LH-NLH rats were used. Synaptosomes were purified by differential
      centrifugation on Percoll gradients and analyzed by two-dimensional
      polyacrylamide gel electrophoresis (2-DE). Protein spots differently regulated in
      the various comparisons were excised from gels and identified by mass
      spectrometry. Proteins involved in energy metabolism and cellular remodeling were
      primarily dysregulated, when LH and NLH rats were compared. Moreover, several
      proteins (aconitate hydratase, pyruvate dehydrogenase E1, dihydropyrimidinase
      related protein-2 and stathmin) were found to be regulated in opposite directions
      by stress and drug treatment. These proteins could represent new molecular
      correlates of both vulnerability to stress and response to drugs, and putative
      targets for the development of novel drugs with antidepressant action. This
      article is part of a Special Issue entitled 'Trends in neuropharmacology: in
      memory of Erminio Costa'.

PMID- 21195719
TI  - Ethanol modulation of synaptic plasticity.
AB  - Synaptic plasticity in the most general terms represents the flexibility of
      neurotransmission in response to neuronal activity. Synaptic plasticity is
      essential both for the moment-by-moment modulation of neural activity in response
      to dynamic environmental cues and for long-term learning and memory formation.
      These temporal characteristics are served by an array of pre- and post-synaptic
      mechanisms that are frequently modulated by ethanol exposure. This modulation
      likely makes significant contributions to both alcohol abuse and dependence. In
      this review, I discuss the modulation of both short-term and long-term synaptic
      plasticity in the context of specific ethanol-sensitive cellular substrates. A
      general discussion of the available preclinical, animal-model based
      neurophysiology literature provides a comparison between results from in vitro
      and in vivo studies. Finally, in the context of alcohol abuse and dependence, the
      review proposes potential behavioral contributions by ethanol modulation of
      plasticity.

PMID- 21195722
TI  - Cortisol reduces cell proliferation in the telencephalon of rainbow trout
      (Oncorhynchus mykiss).
AB  - The fish brain grows throughout life, and new cells are added continuously in all
      major brain areas. As in mammals, the rate of adult brain cell proliferation in
      fish can be regulated by external factors including environmental complexity and
      interaction with conspecifics. We have recently demonstrated that the stress
      experienced by subordinate rainbow trout in social hierarchies leads to a marked
      suppression of brain cell proliferation in the telencephalon, and that this is
      accompanied by an increase in plasma levels of cortisol. Corticosteroid hormones
      are known to suppress adult neurogenesis in mammals, and to investigate whether
      this is also the case in fish, rainbow trout were fed feed containing either a
      low or a high dose of cortisol for 6 days. Compared to control animals receiving
      regular feed, both cortisol treated groups had significantly elevated cortisol
      levels 24h after the last feeding, with the high group having levels comparable
      to those previously reported in socially stressed fish. To quantify cell
      proliferation, immunohistochemistry for proliferating cell nuclear antigen (PCNA)
      was performed to identify actively cycling cells. The density of PCNA-positive
      nuclei in the telencephalon was reduced by about 50% in both cortisol treated
      groups. The effect of cortisol on brain cell proliferation did not reflect a
      general down regulation of growth, as only the high cortisol group had reduced
      growth rate, and there was no correlation between brain cell proliferation and
      growth rate in any group. These results indicate that the reduced proliferative
      activity seen in brains of socially stressed fish is mediated by cortisol, and
      that there is a similar suppressive effect of cortisol on brain cell
      proliferation in the teleost forebrain as in the mammalian hippocampus.

PMID- 21195723
TI  - Brain nuclei in actively courting red-sided garter snakes: a paradigm of neural
      trimorphism.
AB  - During the breeding season, two distinct male phenotypes are exhibited by red
      sided garter snakes (Thamnophis sirtalis parietalis), with courtship behavior
      being directed not only toward females, but also toward a sub-population of males
      called she-males. She-males are morphologically identical to other males except
      for a circulating androgen level three times that of normal males and their
      ability to produce a female-like pheromone. As in other vertebrates, limbic
      nuclei in the red-sided garter snake brain are involved in the control of sexual
      behaviors. For example, an intact anterior hypothalamus pre-optic area (AHPOA) is
      essential for the initiation and maintenance of reproduction. To determine if
      brain morphology varies among the three behavioral phenotypes (i.e., males, she
      males, and females) during the breeding season, we examined the volume, cell size
      and cell density of the AHPOA as well as a control region, the external nucleus
      of the optic tract (ENOT). We used Luxol Fast Blue and Ziehl's Fuchsin to
      visualize neurons and glial cells, respectively. No significant differences were
      observed among the three behavioral phenotypes in the volume, cell size or
      density in the control region. In contrast, the volume, cell size and density of
      the AHPOA of she-males were significantly greater than those of both male and
      female snakes. While the volume of the AHPOA was significantly greater in females
      compared to males, no differences were observed in cell size or density. These
      differences in brain morphology suggest a possible underlying mechanism for
      phenotypic-specific behavioral patterns.

PMID- 21195721
TI  - DISC1-binding proteins in neural development, signalling and schizophrenia.
AB  - In the decade since Disrupted in Schizophrenia 1 (DISC1) was first identified it
      has become one of the most convincing risk genes for major mental illness. As a
      multi-functional scaffold protein, DISC1 has multiple identified protein
      interaction partners that highlight pathologically relevant molecular pathways
      with potential for pharmaceutical intervention. Amongst these are proteins
      involved in neuronal migration (e.g. APP, Dixdc1, LIS1, NDE1, NDEL1), neural
      progenitor proliferation (GSK3beta), neurosignalling (Girdin, GSK3beta, PDE4) and
      synaptic function (Kal7, TNIK). Furthermore, emerging evidence of genetic
      association (NDEL1, PCM1, PDE4B) and copy number variation (NDE1) implicate
      several DISC1-binding partners as risk factors for schizophrenia in their own
      right. Thus, a picture begins to emerge of DISC1 as a key hub for multiple
      critical developmental pathways within the brain, disruption of which can lead to
      a variety of psychiatric illness phenotypes.

PMID- 21195724
TI  - Erlotinib inhibits T-cell-mediated immune response via down-regulation of the c
      Raf/ERK cascade and Akt signaling pathway.
AB  - Erlotinib is a potent inhibitor of epidermal growth factor receptor tyrosine
      kinase and has been demonstrated to treat advanced or metastatic non-small cell
      lung cancer to prolong survival after failure of first-line or second-line
      chemotherapy. However, little is known about its effects on immune system. In the
      present study, we aimed to investigate the immunosuppressive activity of
      erlotinib on T lymphocytes both in vitro and in vivo, and further explore its
      potential molecular mechanism. Erlotinib exerted a significant inhibition on the
      T cell proliferation and activation induced by concanavalin A, anti-CD3 plus anti
      CD28, staphylococcal enterotoxin B or phorbol myristate acetate respectively in a
      concentration-dependent manner and it also inhibited the secretion of the
      proinflammatory cytokines such as IL-2 and IFN-gamma of activated T cells.
      Further study showed that erlotinib caused G0/G1 arrest and suppressed the
      phosphorylations of c-Raf, ERK and Akt in activated T cells. Moreover, erlotinib
      significantly ameliorated picryl chloride-induced ear contact dermatitis in a
      dose-dependent manner in vivo. In summary, these findings suggest that erlotinib
      may cause the impairment of T-cell-mediated immune response both in vitro and in
      vivo through inhibiting T cell proliferation and activation, which is closely
      associated with its potent down-regulation of the c-Raf/ERK cascade and Akt
      signaling pathway.

PMID- 21195725
TI  - Combining vernier acuity and visual backward masking as a sensitive test for
      visual temporal deficits in aging research.
AB  - Performance in many everyday situations slows down when age increases. The causes
      of slowing down may be found on any stage of information processing. Here, we
      show that the combination of a vernier acuity task and the shine-through backward
      masking paradigm is a good paradigm to determine temporal processing deficits.
      The paradigm is relatively robust to optical blur and unlikely affected by motor
      dysfunctions. Strong masking deficits are found from an age of about 50 years on.

PMID- 21195726
TI  - Perceived environmental correlates of physical activity for leisure and
      transportation in Curitiba, Brazil.
AB  - BACKGROUND: Physical activity (PA) has consistently been associated with
      perceived environmental characteristics. OBJECTIVE: To examine the association
      between perceived environmental attributes and various forms of PA in Curitiba,
      Brazil. METHODS: A cross-sectional phone survey of adults was conducted in 2008
      (n=2097). The questionnaire included environmental perceptions and PA. Principal
      components analysis was used to identify groups of perceived environmental
      attributes. Multivariate methods tested the associations of PA with perceived
      environment characteristics. RESULTS: Perceptions of moderate and high personal
      safety were positively associated with walking for transportation (53.0%, 53.1%
      vs. 47.3%, both adjusted ORs [aOR]=1.5). Number of destinations within a 10
      minute walk (4 and >6 vs. <3) was positively associated with bicycling for
      transportation (7.8%, 9.9% vs.4.8%, aOR=2.5). Perception of high accessibility
      was positively associated with MVPA during leisure time (35.1% vs. 19.1, aOR=1.7)
      and meeting recommendations for total PA (58.7% vs. 45.1%, aOR=1.4). Perception
      of high quality of the pedestrian space (57.3% vs. 46.5%, aOR=1.4) and moderate
      levels of personal safety (54.3% vs. 47.6%, aOR=1.3) were also positively
      associated with meeting recommendations for total PA. CONCLUSIONS: Different
      environmental attributes were associated with different PA outcomes, suggesting
      that these relationships are complex and may differ from those in high-income
      countries.

PMID- 21195727
TI  - Human papillomavirus vaccination rates and state mandates for tetanus-containing
      vaccines.
AB  - OBJECTIVE: We sought to examine nationally the association between school
      mandates for adolescent tetanus-containing vaccines (Td and/or Tdap) and
      adolescent female human papillomavirus (HPV) vaccination. METHODS: Each state was
      categorized by whether a school mandate for adolescent Td and/or Tdap vaccines
      was enacted. Mean HPV vaccine series initiation levels among adolescent females
      were compared between each mandate category. RESULTS: Mean HPV vaccine series
      initiation levels were significantly lower in states without Td/Tdap vaccine
      mandates than in those with mandates (42.9% vs. 47.3%; p=0.004). CONCLUSIONS:
      School mandates for adolescent Td/Tdap vaccination may have a carry-over effect
      on HPV vaccination.

PMID- 21195729
TI  - Local cytokine response upon respiratory syncytial virus infection.
AB  - Respiratory syncytial virus (RSV) is the leading cause of childhood
      hospitalization and respiratory distress and has been recognized for several
      decades as a major health and economic burden worldwide. This virus has developed
      several virulence mechanisms to impair the establishment of a protective immune
      response to re-infection. Accordingly, inefficient immunological memory is
      usually generated after exposure to this pathogen. Furthermore, it has been shown
      that RSV can actively promote the induction of an inadequate cellular immune
      response at the site of infection that causes exacerbated inflammation in the
      respiratory tract. Such an inflammatory response is both inefficient for clearing
      the virus and can be responsible for detrimental symptoms, such as asthma and
      wheezing. Recent data suggest that RSV possesses molecular mechanisms to induce
      the secretion of pro-inflammatory cytokines that modulate the immune response and
      impair viral clearance by reducing IFN-gamma production. Here, we discuss recent
      research leading to the identification of RSV virulence factors that are
      responsible of promoting a pro-inflammatory environment at the airways and their
      implications on pathogenicity.

PMID- 21195728
TI  - Socioeconomic status and subclinical atherosclerosis in older adults.
AB  - OBJECTIVE: This study investigated the long-term effects of socioeconomic status
      (SES) on atherosclerosis. METHODS: Data from the Epidemiology of Hearing Loss
      Study and the Beaver Dam Eye Study (Beaver Dam, WI, 1998-2000), were used to
      examine adult SES (education, household income, and longest-held job) and
      childhood SES (household density and parental home ownership at age 13)
      associations with carotid intima-media thickness (IMT) and carotid plaque in a
      cohort of 2042 men and women aged 53 to 94 years. RESULTS: For education, income,
      and occupation (women), those in the lowest SES group had statistically larger
      age-sex-adjusted IMT than those in the highest SES group (<12 vs. >12 years
      education: 0.92 vs. 0.86 mm respectively, P<0.0001), (<$10,000 vs. >$45,000: 0.97
      vs. 0.87 mm, P<0.0001), (operator/fabricator/labor vs. manager/professional: 0.89
      vs. 0.82 mm, P<0.001). Associations were similar using carotid plaque as the
      outcome. Participants with low levels of both adult and childhood SES measures
      had age-sex-adjusted IMT greater than those with persistently high levels of SES
      (0.93 vs. 0.84 mm, P<0.0001). CONCLUSIONS: Measures of SES at two points in the
      life-span were associated with subclinical atherosclerosis.

PMID- 21195730
TI  - Orientation and expression of methicillin-resistant Staphylococcus aureus small
      RNAs by direct multiplexed measurements using the nCounter of NanoString
      technology.
AB  - Staphylococcus aureus is a versatile bacterial opportunist responsible for a wide
      spectrum of infections. Several genomes of this major human pathogen have been
      publicly available for almost 10 years, but comprehensive links between virulence
      or epidemicity and genome content of the bacterium are still missing. This
      project aims at characterizing a set of small transcribed molecules currently
      ignored by standard automated annotation algorithms. We assessed the NanoString's
      nCounter Analysis System for its ability to determine the orientation and
      quantity of the expressed small RNA (sRNA) molecules that we recently detected
      with RNA-Sequencing (RNA-Seq). The expression of approximately seventy small
      RNAs, including sRNA localized in pathogenic islands, was assessed at 5 time
      points during growth of the bacterium in a rich medium. In addition, two
      extraction strategies were tested: RNA was either purified on columns or simply
      prepared from crude lysates in the presence of a chaotropic buffer. The nCounter
      System allowed us to perform these 64 measurements in a single experiment,
      without any enzymatic reaction, thus avoiding well-known technical biases. We
      evaluated the reproducibility and reliability of the nCounter compared to
      quantitative RT-PCR (RT-qPCR). By using two different designs for the two coding
      strands, we were able to identify the coding strand of 61 small RNA molecules
      (95%). Overall, the nCounter System provided an identification of the coding
      strand in perfect concordance with RNA-Seq data. In addition, expression results
      were also comparable to those obtained with RT-qPCR. The sensitivity and minimal
      requirements of the nCounter system open new possibilities in the field of gene
      expression analysis, for assessing bacterial transcript profiles from complex
      media (i.e. during host-pathogen interactions) or when starting from poorly
      purified RNA or even directly from lysed infected tissues.

PMID- 21195731
TI  - The use of soluble African horse sickness viral protein 7 as an antigen delivery
      and presentation system.
AB  - We have investigated the use of soluble chimeric trimers of the major capsid
      protein VP7 of African horse sickness virus (AHSV) as a vaccine delivery system
      by targeting some of the natural hydrophilic loops on the VP7 top domain for the
      insertion of foreign peptides. Key to this trimer display strategy is the
      solubility of AHSV VP7 and how the solubility of this hydrophobic protein can be
      manipulated by inserting peptides into the top domain. To investigate, we
      generated different cloning vectors by inserting multiple cloning sites at three
      different positions in the VP7 gene. These modifications inserted six amino acids
      at the cloning sites and in some cases this converted VP7 to a largely soluble
      protein without affecting the ability of the modified proteins to form trimers.
      The vectors were used to generate a number of soluble VP7 fusion proteins
      including a fusion with a 36 amino acid insert that overlaps important
      immunological domains on protein VP1 of foot and mouth disease virus (FMDV) as
      well as a 110 amino acid peptide derived from AHSV VP2. Soluble trimers of these
      fusion proteins were able to elicit a good insert-specific immune response in
      guinea pigs. l-Arginine was found to reverse protein aggregation and was employed
      as an effective strategy to isolate relatively pure soluble chimeric VP7 trimers.
      Another factor that increased VP7 solubility in both wild-type VP7 and one of the
      VP7 vector proteins was the substitution of the leucine residue in position 345
      of the VP7 C-terminus with a hydrophilic arginine residue.

PMID- 21195732
TI  - Reassortment between seasonal and swine-origin H1N1 influenza viruses generates
      viruses with enhanced growth capability in cell culture.
AB  - One year after the emergence of the 2009 influenza (H1N1) pandemic, most cases
      have been relatively mild; however, the possibility of enhanced viral growth
      ability by reassortment with seasonal viruses cannot be overlooked. Here, we show
      that reassortant viruses containing a seasonal H1 HA and swine-origin NA and M
      genes have enhanced virus growth over their wild-type parental viruses. The
      emergence of such viruses in nature could, therefore, represent a threat.

PMID- 21195733
TI  - Cell death gene expression profile: role of RIPK2 in dengue virus-mediated
      apoptosis.
AB  - Dengue virus (DENV) is a major emerging arthropod-borne pathogen, which infects
      individuals in both subtropical and tropical regions. Patients with DENV
      infection exhibit evidence of hepatocyte injury. However, the mechanisms of
      hepatocyte injury are unclear. Therefore we examined the expression of cell death
      genes during DENV-infection of HepG2 cells using real-time PCR arrays. The
      expression changes were consistent with activation of apoptosis and autophagy.
      Expression of the up-regulated genes, including RIPK2, HRK, TGF-beta, PERK, and
      LC3B, was confirmed by quantitative real-time PCR. RIPK2 belongs to the receptor
      interacting protein family of serine/threonine protein kinases, which is a
      crucial mediator of multiple stress responses that leads to the activation of
      caspase, NF-kappaB and MAP kinases including JNK and p38. RIPK2 activity is
      inhibited by the p38 MAPK pathway inhibitor SB203580. The effect of SB203580 on
      RIPK2 expression and DENV-induced apoptosis was tested in DENV-infected HepG2
      cells. The inhibition of RIPK2 expression by SB203580 significantly reduced
      apoptosis. SB203580 also significantly reduced DENV capsid protein (DENVC)
      mediated apoptosis. Suppression of endogenous RIPK2 in DENV-infected HepG2 cells
      by small interfering RNA (siRNA) significantly decreased apoptosis suggesting for
      the first time that RIPK2 plays a role in DENV-mediated apoptosis.

PMID- 21195734
TI  - WITHDRAWN: Caprine antibodies towards E2 conserved peptides interfere with
      hepatitis C virus infectivity in vitro.
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- 21195735
TI  - So similar, yet so different: selective translation of capped and polyadenylated
      viral mRNAs in the influenza virus infected cell.
AB  - Influenza virus is included among the Orthomyxoviridae family and it is a major
      public health problem causing annual mortality worldwide. Viral mRNAs bear short
      capped oligonucleotide sequences at their 5'-ends, acquired from host cell pre
      mRNAs during viral transcription, and are polyadenylated at their 3'-end.
      Therefore, viral and cellular mRNAs are undistinguishable from a structural point
      of view. However, selective translation of viral proteins occurs upon infection,
      while initiation and elongation steps of cellular mRNA translation are
      efficiently inhibited. Viruses do not possess the complex machinery required to
      translate their mRNAs and are then obliged to compete for host-cell factors and
      manipulate the translation apparatus to their own benefit. Thus, the
      understanding of the processes that govern viral translation could facilitate the
      finding of possible targets for anti viral interventions. In the present review,
      we will point out the mechanisms by which influenza virus takes control of the
      host-cell protein synthesis machinery to ensure the production of new viral
      particles. First, we will discuss the mechanisms by which the virus counteracts
      the anti viral translation repression induced in the infected cell. Next, we will
      focus on the shut-off of cellular protein synthesis and the specific requirements
      for the eIF4F complex on influenza mRNA translation. Finally, we will discuss the
      role of different cellular and viral proteins in the selective translation of
      viral messengers in the infected cell and we will summarize the proposed
      mechanisms for the recruitment of cellular translational machinery to the viral
      mRNAs.

PMID- 21195736
TI  - siRNA nanocarriers based on methacrylic acid copolymers.
AB  - Poly(ethylene glycol)-b-poly(propyl methacrylate-co-methacrylic acid) (PEG-b
      P(PrMA-co-MAA) can be complexed with poly(amido amine) (PAMAM) dendrimers and
      nucleic acids to form pH-responsive nanosized core-shell type polyion complex
      micelles (PICMs). These PICMs have the ability to lose their shell and release
      the PAMAM/nucleic acid core under mildly acidic conditions such as those
      encountered in the endosomal compartment. In this work, pH-sensitive PICMs
      composed of PEG-b-P(PrMA-co-MAA), different PAMAMs, and siRNAs were prepared and
      characterized. These micelles had mean diameters ranging from 50 to 100 nm
      depending on the structure of the polycationic component. In order to trigger
      PICM uptake by receptor-mediated endocytosis, the micelles were decorated with an
      antibody fragment directed against the transferrin receptor (anti-CD71). The
      targeting ligand was stably conjugated to a semi-telechelic amino-PEG-b-P(PrMA-co
      MAA) via a maleimide/activated ester bifunctional linker, yielding up to 60%-80%
      functionalization of the maleimide groups. The cellular uptake of the micelles
      was assessed on human prostate cancer cells (PC-3) via flow cytometry. Native
      PICMs and micelles bearing a non-specific antibody fragment were taken up to the
      same extent with a low efficiency, whereas anti-CD71 Fab'-decorated PICMs
      exhibited significantly higher uptake. The capacity of the targeted, siRNA
      loaded, PICMs to downregulate the expression of the Bcl-2 anti-apoptotic
      oncoprotein was investigated using the appropriate unmodified or 2'-modified (2'F
      RNA and 2'F-ANA) siRNA sequence. Bcl-2 mRNA and protein levels were greatly
      reduced when the cells were transfected with anti-CD71 decorated PICMs. Optimal
      silencing was achieved with the chemically modified siRNA. These data suggest
      that combining optimized siRNA chemistry with an effective delivery system can
      potentiate the activity of siRNA, thereby potentially reducing the total dose of
      carrier required to achieve a pharmacological effect.

PMID- 21195737
TI  - Mucin from rheumatoid arthritis synovial fluid enhances interleukin-6 production
      by human peripheral blood mononuclear cells.
AB  - The carbohydrate chains represented by mucins (MUCs) are expressed by a variety
      of normal and malignant secretory epithelial cells and induce a variety of
      immunoreactions. To find new mucins related to the pathogenesis of rheumatoid
      arthritis (RA), we examined high-molecular-weight molecules inducing cytokines on
      human peripheral blood mononuclear cells (PBMCs) in synovial fluid from affected
      joints. We found a high-molecular-weight substance that induces interleukin 6
      production on PBMCs in RA synovial fluid on gel filtration. MUC-1 was present in
      the resulting fractions, although they had been purified by CsCl density gradient
      centrifugation. We also found that MUC-1 was expressed on synovial cells and
      infiltrating inflammatory mononuclear cells on the sublining layer and lymphoid
      follicles in RA synovial tissues. CD68-positive superficial synovial cells
      colocalized with MUC-1 and CD68-positive macrophages were in contact with MUC-1
      positive mononuclear cells. These findings imply that mucins, including MUC-1,
      may be related to immunoinflammatory reactions in the pathogenesis of RA.

PMID- 21195738
TI  - Association of an IL-4 gene haplotype with Graves disease in children:
      experimental study and meta-analysis.
AB  - Investigations of an association between Graves disease (GD) and the IL-4 gene
      have yielded conflicting results. We performed a case-control study of IL-4 gene
      polymorphisms possibly associated with GD, as well as a meta-analysis of other
      such studies. We genotyped IL-4 single nucleotide polymorphisms (SNPs) rs2243250
      and rs2243289 in 220 unrelated children with GD and 904 healthy controls. No
      significant differences between patients and controls were observed in the
      genotype, allele, or carrier frequencies of the 2 SNPs. The levels of
      autoantibodies did not differ significantly between the genotypes of each SNP.
      Linkage disequilibrium between the 2 SNPs was strong in the controls (D', 0.916;
      r(2), 0.824). Haplotype TA conferred a significant risk of GD (odds ratio = 2.47,
      95% confidence interval 1.24-4.95, corrected p value = 0.033). The T allele
      frequency of rs2243250 was 80.0% in Asians, significantly higher than the 12.6%
      in Caucasians (p = 1.4 * 10(-269)). Meta-analysis of data from 8 published
      reports and our own study did not reveal any significant association between
      these SNPs and GD. Our study showed an association between the IL-4 gene and GD
      in children, but only using a haplotype-based method, suggesting that this might
      be a better approach than evaluating individual SNPs.

PMID- 21195739
TI  - Isolation and phenotypic characterization of a multinucleated tartrate-resistant
      acid phosphatase-positive bone marrow macrophage.
AB  - OBJECTIVE: Prothrombin (PT) and osteopontin (OPN) promote adhesion of bone
      derived tartrate-resistant acid phosphatase (TRAP, Acp5)-positive multinucleated
      cells differing in size, morphology, and resorptive activity. Here we explored
      phenotypic and functional differences between these cells. MATERIALS AND METHODS:
      Global-wide and TRAP (Acp5) promoter messenger RNA expression, ability for
      phagocytosis, macrophage colony-stimulating factor-dependent migration, and in
      situ localization of these cells were investigated. RESULTS: Gene expression of
      PT-adherent cells was skewed toward expression of innate immune response,
      phagocytosis, and scavenger receptor genes. They avidly phagocytosed
      Staphylococcus aureus and Dextran particles, and their migration on PT was
      enhanced by macrophage colony-stimulating factor. In contrast, OPN-adherent cells
      lacked ability to phagocytose particles and their migration on OPN was inhibited
      by macrophage colony-stimulating factor. They expressed typical osteoclast
      proteases implicated in bone matrix degradation, such as the collagenases
      cathepsin K; matrix metalloprotease-2; -9; -13; and -14, consistent with their
      high bone resorptive activity in vitro. In addition, OPN-adherent cells
      predominantly expressed the PU.1/MiTF/NFATc1-driven TRAP exon 1C messenger RNA,
      whereas PT-adherent cells preferably expressed TRAP exon 1B messenger RNA.
      Furthermore, CD163/cathepsin-K immunohistochemistry demonstrated that PT-adherent
      cells were predominantly located in the diaphyseal bone marrow compartment,
      whereas the OPN-adherent cells were attached to cortical and distal metaphyseal
      trabecular bone surfaces. CONCLUSIONS: This study identifies differences in
      expression of several osteoclast and macrophage genes, as well as functional
      differences between PT- and OPN-adherent cells. We conclude that the OPN-adherent
      cells display osteoclast characteristics, especially with regard to expression of
      matrix-degrading enzymes, whereas the PT-adherent cell might represent a unique
      TRAP-positive multinucleated bone marrow macrophage implicated in immune
      recognition and phagocytosis.

PMID- 21195740
TI  - Effect of filaments within the synaptic cleft on the response of excitatory
      synapses simulated by computer experiments.
AB  - Mathematical models of the excitatory synapse are furnishing valuable information
      about the synaptic response. Based on Brownian-diffusion of glutamate molecules,
      a synapse model was utilized to investigate the synaptic response on a femto
      second time scale by the use of a parallel computer. In particular, the presence
      of fibrils crossing the synaptic cleft was simulated, which could have a role in
      shaping the brain activity. To this aim the model of synapse was modified by
      considering trans-synaptic filaments with diameters ranging from 7 nm to 3 nm,
      disposed on a grid with spacing of 14 nm or 8 nm. The simulation demonstrated
      that the presence of filaments induced an increase in the synaptic response, most
      likely linked to an increment in the probability of encounter between glutamate
      molecules and receptors. The increase was small--from 5 to 20%, but metabolic and
      functional considerations provide substantive hints about the importance of these
      small changes for brain activity. Moreover, it was shown that the presence of
      filaments made more stable the response of the synapse to random variations of
      pre-synaptic elements. Originated by these computational results, some inferences
      about the biological bases of mind diseases such as autism, mental retardation
      and schizophrenia, are reported in the Discussion.

PMID- 21195741
TI  - Tramadol increases extracellular levels of serotonin and noradrenaline as
      measured by in vivo microdialysis in the ventral hippocampus of freely-moving
      rats.
AB  - Tramadol is an atypical opioid with monoamine re-uptake inhibition properties.
      The aim of the current study was to compare, using in vivo microdialysis, the
      effect of tramadol on extracellular serotonin (5-HT) and noradrenaline (NA)
      levels in the rat ventral hippocampus with the effects of the dual 5-HT/NA
      inhibitors (SNRIs) duloxetine and venlafaxine, the tricyclic antidepressant
      clomipramine, the selective 5-HT re-uptake inhibitor (SSRI) citalopram, and the
      selective NA re-uptake inhibitor (NRI) reboxetine. It was found that tramadol,
      duloxetine and venlafaxine increased extracellular levels of both, 5-HT and NA,
      in a dose-dependent manner. Clomipramine also increased extracellular 5-HT and NA
      levels, however not dose-dependently in the tested dose range. Citalopram
      selectively increased extracellular 5-HT levels. Reboxetine increased
      extracellular NA levels and also to a minimal degree 5-HT levels. It can be
      concluded that, albeit less efficacious, the effects of tramadol on serotonergic
      and noradrenergic neurotransmission resemble those of the dual 5-HT and NA re
      uptake inhibitors duloxetine, venlafaxine, and clomipramine, and are different
      from those of the SSRI citalopram and the NRI reboxetine.

PMID- 21195742
TI  - Disruption of MT impairs motion processing.
AB  - Functional magnetic resonance imaging (fMRI) studies have associated motion
      processing with cortical region MT+, which includes sub-region MT that
      preferentially processes motion in the contralateral visual field. Transcranial
      magnetic stimulation (TMS) has been used to temporarily disrupt MT+ which
      impaired motion perception, suggesting this region is necessary for motion
      processing. In the present study, we used fMRI guided TMS to disrupt MT and
      determine whether this sub-region is necessary for motion processing. On an
      individual participant basis, MT was localized in each hemisphere using motion
      related fMRI activity on the posterior bank of the ascending limb of the inferior
      temporal sulcus. In the first experiment, 1 Hz TMS of left MT preferentially
      impaired motion detection in the contralateral versus ipsilateral visual field.
      In the second experiment, single-pulse TMS of MT impaired motion processing to a
      greater degree than color processing. These results provide convergent evidence
      that sub-region MT is necessary for motion processing.

PMID- 21195743
TI  - Antinociceptive effect of intrathecal cannabinoid receptor agonist WIN 55,212-2
      in a rat bone tumor pain model.
AB  - Bone tumor pain is a poorly controlled pain comprising background and severe pain
      on moving or weight-bearing postures that decreases the quality of life for
      cancer patients; thus, more effective analgesics are clearly needed. This study
      evaluated the efficacy of a cannabinoid (CB) receptor agonist (WIN 55,212-2) on
      bone tumor pain in the spinal cords of rats, and clarified the roles of the CB1
      and CB2 receptors in WIN 55,212-2-induced antinociception at the spinal level.
      Bone tumor pain was induced by injecting MRMT-1 tumor cells (1*10(5)) into the
      right tibias of female Sprague-Dawley rats under sevoflurane anesthesia. Bone
      tumor development was monitored radiologically. Under sevoflurane anesthesia, a
      polyethylene catheter was inserted into the intrathecal space for drug
      administration. To assess pain, the withdrawal threshold was measured by applying
      a von Frey filament to the tumor cell inoculation site. The effect of intrathecal
      WIN 55,212-2 was investigated. Next, the WIN 55,212-2-mediated antinociception
      was reversed using CB1 (AM 251) and CB2 (AM 630) receptor antagonists. The
      intratibial injection of MRMT-1 tumor cells produced radiologically confirmed
      bone tumors. The paw withdrawal threshold decreased significantly (mechanical
      allodynia) with tumor development; however, intrathecal WIN 55,212-2 dose
      dependently increased the withdrawal threshold. The antinociceptive effect of WIN
      55,212-2 was reversed by both CB1 and CB2 receptor antagonists. Intrathecal WIN
      55,212-2 reduced bone tumor-related pain behavior mediated via spinal CB1 and CB2
      receptors. Therefore, spinal CB receptor agonists may be novel analgesics in the
      treatment of bone tumor pain.

PMID- 21195744
TI  - The general anesthetic sevoflurane affects the expression of clock gene mPer2
      accompanying the change of NAD+ level in the suprachiasmatic nucleus of mice.
AB  - Sevoflurane is an anesthetic for the general anesthesia. In this study, we showed
      that sevoflurane anesthesia affects the expression of mouse Per2 (mPer2), which
      is a clock gene in the brain which is considered the organ where the anesthetics
      act in. 64.5% of mPer2 circadian expression was repressed under anesthesia in the
      suprachiasmatic nucleus (SCN) of the brain. After recovering from the anesthesia,
      the repressed mPer2 expression was restored to the same level as in non
      anesthesia-treated mice. This repression pattern was also observed in the
      subsequent phases of diurnal mPer2 expression. However, obvious phase-shift in
      the mPer2 expression was not showed in this study. On the other hand, the
      behavior analysis in this experiment exhibited that the phases in the circadian
      behavioral rhythm were shifted backwards. We also measured the NAD(+) level in
      the SCN, which was a mediator regulating the mPer2 expression. Then, significant
      increase of NAD(+) was detected under the anesthesia. These results indicate that
      the anesthesia induces the increase of NAD(+), and consequently leads to the
      repression of mPer2 expression and modifies the circadian expression pattern and
      diurnal behavioral rhythm of mice. Furthermore, the modification of mPer2
      expression by the anesthesia is considered to affect various gene expressions.

PMID- 21195745
TI  - The response of spinal microglia to chemotherapy-evoked painful peripheral
      neuropathies is distinct from that evoked by traumatic nerve injuries.
AB  - Painful peripheral neuropathies produced by nerve trauma are accompanied by
      substantial axonal degeneration and by a response in spinal cord microglia that
      is characterized by hypertrophy and increased expression of several intracellular
      and cell-surface markers, including ionizing calcium-binding adapter molecule 1
      (Iba1) and Cd11b (a complement receptor 3 antigen recognized by the OX42
      antibody). The microglia response has been hypothesized to be essential for the
      pathogenesis of the neuropathic pain state. In contrast, the painful peripheral
      neuropathies produced by low doses of cancer chemotherapeutics do not produce
      degeneration of axons in the peripheral nerve, although they do cause partial
      degeneration of the sensory axons' distal-most tips, that is the intraepidermal
      nerve fibers that form the axons' terminal receptor arbors. The question thus
      arises as to whether the relatively minor and distal axonal injury characterizing
      the chemotherapy-evoked neuropathies is sufficient to evoke the microglial
      response that is seen after traumatic nerve injury. We examined the lumbar spinal
      cord of rats with painful peripheral neuropathies due to the anti-neoplastic
      agents, paclitaxel, vincristine, and oxaliplatin, and the anti-retroviral agent,
      2',3'-dideoxycytidine (ddC), and compared them to rats with a complete sciatic
      nerve transection and the partial sciatic nerve injury produced in the chronic
      constriction injury model (CCI). As expected, microglia hypertrophy and increased
      expression of Iba1 were pronounced in the nerve transection and CCI animals.
      However, there was no microglia hypertrophy or increased Iba1 staining in the
      animals treated with paclitaxel, vincristine, oxaliplatin, or ddC. These results
      suggest that the mechanisms that produce neuropathic pain after exposure to
      chemotherapeutics may be fundamentally different than those operating after nerve
      trauma.

PMID- 21195746
TI  - Alteration of the endocannabinoid system in mouse brain during prion disease.
AB  - Prion diseases are neurodegenerative disorders characterized by deposition of the
      pathological prion protein (PrPsc) within the brain of affected humans and
      animals. Microglial cell activation is a common feature of prion diseases;
      alterations of various neurotransmitter systems and neurotransmission have been
      also reported. Owing to its ability to modulate both neuroimmune responses and
      neurotransmission, it was of interest to study the brain endocannabinoid system
      in a prion-infected mouse model. The production of the endocannabinoid, 2
      arachidonoyglycerol (2-AG), was enhanced 10 weeks post-infection, without
      alteration of the other endocannabinoid, anandamide. The CB2 receptor expression
      was up-regulated in brains of prion-infected mice as early as 10 weeks and up to
      32 weeks post-infection whereas the mRNAs of other cannabinoid receptors (CBRs)
      remain unchanged. The observed alterations of the endocannabinoid system were
      specific for prion infection since no significant changes were observed in the
      brain of prion-resistant mice, that is, mice devoid of the Prnp gene. Our study
      highlights important alterations of the endocannabinoid system during early
      stages of the disease long before the clinical signs of the disease.

PMID- 21195747
TI  - Pre-synaptic histamine H3 receptors modulate glutamatergic transmission in rat
      globus pallidus.
AB  - The globus pallidus, a neuronal nucleus involved in the control of motor
      behavior, expresses high levels of histamine H(3) receptors (H(3)Rs) most likely
      located on the synaptic afferents to the nucleus. In this work we studied the
      effect of the activation of rat pallidal H(3)Rs on depolarization-evoked
      neurotransmitter release from slices, neuronal firing rate in vivo and turning
      behavior. Perfusion of globus pallidus slices with the selective H(3)R agonist
      immepip had no effect on the release of [(3)H]-GABA ([(3)H]-gamma-aminobutyric
      acid) or [(3)H]-dopamine evoked by depolarization with high (20 mM) K(+), but
      significantly reduced [(3)H]-d-aspartate release (-44.8 +/- 2.6% and -63.7 +/-
      6.2% at 30 and 100 nM, respectively). The effect of 30 nM immepip was blocked by
      10 MUM of the selective H(3)R antagonist A-331440 (4'-[3-[(3(R)-dimethylamino-1
      pyrrolidinyl]propoxy]-[1,1-biphenyl]-4'-carbonitrile). Intra-pallidal injection
      of immepip (0.1 MUl, 100 MUM) decreased spontaneous neuronal firing rate in
      anaesthetized rats (peak inhibition 68.8+/-10.3%), and this effect was reversed
      in a partial and transitory manner by A-331440 (0.1 MUl, 1 mM). In free-moving
      rats the infusion of immepip (0.5 MUl; 10, 50 and 100 MUM) into the globus
      pallidus induced dose-related ipsilateral turning following systemic apomorphine
      (0.5 mg/kg, s.c.). Turning behavior induced by immepip (0.5 MUl, 50 MUM) and
      apomorphine was partially prevented by the local injection of A-331440 (0.5 MUl,
      1 mM) and was not additive to the turning evoked by the intra-pallidal injection
      of antagonists at ionotropic glutamate receptors (0.5 MUl, 1 mM each of AP-5, dl
      2-amino-5-phosphonovaleric acid, and CNQX, 6-nitro-7
      sulphamoylbenzo[f]quinoxaline-2,3-dione). These results indicate that pre
      synaptic H(3)Rs modulate glutamatergic transmission in rat globus pallidus and
      thus participate in the control of movement by basal ganglia.

PMID- 21195748
TI  - Location of glutamatergic/aspartatergic neurons projecting to the hypothalamic
      ventromedial nucleus studied by autoradiography of retrogradely transported [3H]D
      aspartate.
AB  - The hypothalamic ventromedial nucleus is a prominent cell group, which is
      involved in the control of feeding, sexual behavior and cardiovascular function
      as well as having other functions. The nucleus receives inputs from various
      forebrain structures and has a dense glutamatergic innervation. The aim of the
      present investigations was to reveal the location of glutamatergic neurons in the
      telencephalon and diencephalon projecting to this hypothalamic cell group.
      [(3)H]d-aspartate retrograde autoradiography was used injecting the tracer into
      the ventromedial nucleus. We detected radiolabeled neurons in telencephalic
      structures including the lateral septum, bed nucleus of the stria terminalis and
      the amygdala, and in various diencephalic regions, such as the medial preoptic
      area, hypothalamic paraventricular nucleus, periventricular nucleus, anterior
      hypothalamic area, ventral premamillary nucleus, thalamic paraventricular and
      parataenial nuclei and in the hypothalamic ventromedial nucleus itself. Our
      observations are the first data on the location of glutamatergic neurons
      terminating in the hypothalamic ventromedial nucleus. The findings indicate that
      glutamatergic innervation of the ventromedial nucleus is very complex.

PMID- 21195749
TI  - Rapid brain-derived neurotrophic factor-dependent sequestration of amygdala and
      hippocampal GABA(A) receptors via different tyrosine receptor kinase B-mediated
      phosphorylation pathways.
AB  - During the consolidation of fear memory, it has been shown that GABA(A) receptors
      (GABA(A)R) are rapidly downregulated in amygdala. This rapid decrease in GABA(A)R
      functioning may permit transient hyperexcitablity, contributing to cellular
      mechanisms of memory consolidation. Memory consolidation also requires brain
      derived neurotrophic factor (BDNF) activation of tyrosine receptor kinase B
      (TrkB) receptors in the amygdala and hippocampus. We hypothesized that rapid
      internalization of GABA(A)Ralpha1 is mediated via TrkB activation of PKA and PKC
      dependent processes. Primary neuronal cell cultures, from postnatal day 14-21
      mouse amygdala and hippocampus, were analyzed with immunofluorescence using cell
      surface, whole-cell permeabilization, and antibody internalization techniques, as
      well as with (3)H-muscimol binding assays. In both hippocampal and amygdala
      cultures, we found a >60% reduction in surface GABA(A)Ralpha1 within 5 min of
      BDNF treatment. Notably, the rapid decrease in surface GABA(A)Ralpha1 was
      confirmed biochemically using surface biotinylation assays followed by western
      blotting. This rapid effect was accompanied by TrkB phosphorylation and increased
      internal GABA(A)Ralpha1 immunofluorescence, and was blocked by k252a, a broad
      spectrum tyrosine kinase antagonist. To further demonstrate TrkB specificity, we
      used previously characterized TrkB(F616A) mice, in which the highly selective
      TrkB-mutant specific antagonist, 1NMPP1, prevented the BDNF-dependent
      GABA(A)Ralpha1 internalization. In hippocampus, we found both PKA and PKC
      inhibition, using Rp-8-Br-cAMP and Calphostin C, respectively, blocked
      GABA(A)Ralpha1 internalization, whereas inhibition of MAPK (U0126) and PI3K
      (LY294002) did not prevent rapid internalization. By contrast in amygdala
      cultures, Rp-8-Br-cAMP had no effect. Together, these data suggest that rapid
      GABA(A)R internalization during memory consolidation is BDNF-TrkB dependent.
      Further, it appears that hippocampal GABA(A)R internalization is PKA and PKC
      dependent, while it may be primarily PKC dependent in amygdala, implying
      differential roles for TrkB-dependent kinase activation in BDNF-dependent memory
      formation.

PMID- 21195750
TI  - Noradrenaline enhances ATP P2X3 receptor expression in dorsal root ganglion
      neurons of rats.
AB  - Increasing evidence indicates that both the ATP P2X receptors and adrenergic
      systems play a very important role in the development of nociception. However,
      there is little information concerning the interactions between these two systems
      in the dorsal root ganglia (DRG). In the present study, we examined the effects
      of noradrenaline (NA) on the P2X3 receptor expression in the DRG of Sprague
      Dawley rats. The direct effect of NA on the P2X3 mRNA and protein expression was
      determined in cultured DRG neurons. Treatment of neuronal cultures with NA (50
      nM, 5 h) induced a two-fold increase in P2X3 expression, as detected with real
      time RT-PCR and Western blots, but had no effect on P2X2 expression. In
      electrophysiological experiments, perfusion of neuronal cultures with the P2X3
      agonist (alphabeta-methylene ATP) increased neuronal firing rate by 139% and 273%
      in neurons treated with either PBS (control) or NA, respectively, indicating that
      chronic NA treatment significantly enhanced the neuronal response to P2X3
      activation. In behavior studies, combination of NA (2 or 20 nmol) with alphabeta
      methylene ATP (10 nmol) produced a significant and long lasting augmentation of
      thermal hyperalgesia. These results indicate that NA stimulates P2X3 expression
      in DRG neurons, and this could contribute to the development of pain
      sensitization.

PMID- 21195751
TI  - Genetic disruption of Met signaling impairs GABAergic striatal development and
      cognition.
AB  - The largest structure of the basal ganglia, the striatum, modulates motor
      activity and cognitive function and is composed of GABAergic projection neurons
      and interneurons. To better understand the mechanisms underlying the development
      of the striatal neurons and their assembly into functional circuits, we used a
      mouse with a targeted conditional Met mutation in post-mitotic cells of the
      ventral telencephalon. Characterization of the ontogeny of the striatal neuronal
      populations demonstrated that disruption of Met signaling specifically altered
      the GABAergic interneurons. Medium spiny neurons (MSNs) and cholinergic
      interneurons were largely unaffected. Mice lacking Met signaling have increased
      numbers of striatal GABAergic interneurons in the lateral sensorimotor areas with
      distinct behavioral deficits. Motor function and memory formation and
      consolidation appeared intact, but procedural learning on the cued task of the
      Morris water maze was delayed. MET is a susceptibility gene in Tourette syndrome
      and autism, which are human disorders with impaired procedural learning. This
      study reveals how a striatal targeted disruption in Met signaling after
      generation of striatal neurons produces behavioral phenotypes shared by Tourette
      syndrome and autism, linking the human genetics with the mechanism underlying the
      disorders.

PMID- 21195752
TI  - Altered profile and D2-dopamine receptor modulation of high voltage-activated
      calcium current in striatal medium spiny neurons from animal models of
      Parkinson's disease.
AB  - In the present work we analyzed the profile of high voltage-activated (HVA)
      calcium (Ca2+) currents in freshly isolated striatal medium spiny neurons (MSNs)
      from rodent models of both idiopathic and familial forms of Parkinson's disease
      (PD). MSNs were recorded from reserpine-treated and 6-hydroxydopamine (6-OHDA)
      lesioned rats, and from DJ-1 and PINK1 (PTEN induced kinase 1) knockout (-/-)
      mice. Our analysis showed no significant changes in total HVA Ca2+ current.
      However, we recorded a net increase in the L-type fraction of HVA Ca2+ current in
      dopamine-depleted rats, and of both N- and P-type components in DJ-1-/- mice,
      whereas no significant change in Ca2+ current profile was observed in PINK1-/-
      mice. Dopamine modulates HVA Ca2+ channels in MSNs, thus we also analyzed the
      effect of D1 and D2 receptor activation. The effect of the D1 receptor agonist
      SKF 83822 on Ca2+ current was not significantly different among MSNs from control
      animals or PD models. However, in both dopamine-depleted rats and DJ-1-/- mice
      the D2 receptor agonist quinpirole inhibited a greater fraction of HVA Ca2+
      current than in the respective controls. Conversely, in MSNs from PINK1-/- mice
      we did not observe alterations in the effect of D2 receptor activation.
      Additionally, in both reserpine-treated and 6-OHDA-lesioned rats, the effect of
      quinpirole was occluded by the selective L-type Ca2+ channel blocker nifedipine,
      while in DJ-1-/- mice it was mostly occluded by omega-conotoxin GVIA, blocker of
      N-type channels. These results demonstrate that both dopamine depletion and DJ-1
      deletion induce a rearrangement in the HVA Ca2+ channel profile, specifically
      involving those channels that are selectively modulated by D2 receptors.

PMID- 21195753
TI  - Comparison of chemical-induced transcriptional activation of fish and human
      estrogen receptors: regulatory implications.
AB  - Under the current EU chemical regulation REACH (Registration, Evaluation,
      Authorization and Restriction of Chemicals), revised plant protection products
      and biocides directives, evaluation of endocrine disrupting properties of
      chemicals becomes a regulatory need. Transcriptional activation (TA) testing of
      estrogen receptors (ERs) could be one important first step in the screening and
      testing of endocrine disrupting chemicals (EDCs) for regulatory purposes. However
      up to now there is no consensus on which species or subtype of ERs should be used
      for TA testing. This study collected data from publications on TA testing with
      fish and human ERs for 90 chemicals, covering strong, moderate, and weak or non
      ER binders. Each chemical has been reported at least twice, with differential ER
      TA values that result from different cellular contexts, from intra-/inter-species
      and subtypes of ERs and from intra-/inter-laboratory differences. All assays
      could distinguish the differential transcriptional activity induced by chemicals
      of strong, moderate, and weak or non-ER binders. It is concluded that
      transactivation of ERs in one vertebrate species or one subtype of ERs could be
      extrapolated to other species or subtypes of ERs for the purpose of chemical
      screening. It is emphasized that results from ER TA assays can only be used in a
      weight-of-evidence approach for further testing in regulatory programs. These
      results are of importance for regulatory testing strategies and decision making
      for EDCs.

PMID- 21195754
TI  - The iron-chelating drug triapine causes pronounced mitochondrial thiol redox
      stress.
AB  - Triapine (Tp) is an iron chelator with activity against several types of cancer.
      Iron-Tp [Fe(III)(Tp)(2)] can be redox-cycled to generate reactive oxygen species
      that may contribute to its cytotoxicity. However, evidence for this mechanism in
      cells is limited. The cytosolic and mitochondrial thioredoxins (Trx1 and Trx2,
      respectively) are essential for cell survival. They are normally maintained in
      the reduced state, and support the function of many intracellular proteins
      including the peroxiredoxins (Prxs). Their redox status can indicate oxidant
      stress in their respective subcellular compartments. Tp treatment of human lung
      A549 cells caused almost complete oxidation of Trx2 and its dependent
      peroxiredoxin (Prx3), but there was no effect on Trx1 redox status. Significant
      inhibition of total TrxR activity did not occur until Tp levels were 4-fold above
      those needed to cause Trx2 oxidation. While Tp caused a 36-45% decline in reduced
      glutathione (GSH) levels, GSH accounted for >99% of the total glutathione in the
      absence and presence of Tp. In vitro studies demonstrated that cysteine reduces
      Fe(III)(Tp)(2) to Fe(II)(Tp)(2), and cysteine was faster and more efficient than
      reduced glutathione (GSH) in this regard. Fe(III)(Tp)(2) also mediated the
      oxidation of purified Trx2 in vitro. Thus, Fe(III)(Tp)(2) itself, and/or various
      reactive species that may result from its redox cycling, could account for Trx2
      and Prx3 oxidation in Tp-treated cells. The striking difference between the
      effects on Trx2 and Trx1 implies a pronounced thiol redox stress that is largely
      directed at the mitochondria. These previously unrecognized effects of Tp could
      contribute to its overall cytotoxicity.

PMID- 21195755
TI  - Effects of vestibular prosthesis electrode implantation and stimulation on
      hearing in rhesus monkeys.
AB  - To investigate the effects of vestibular prosthesis electrode implantation and
      activation on hearing in rhesus monkeys, we measured auditory brainstem responses
      (ABR) and distortion product otoacoustic emissions (DPOAE) in four rhesus monkeys
      before and after unilateral implantation of vestibular prosthesis electrodes in
      each of 3 left semicircular canals (SCC). Each of the 3 left SCCs were implanted
      with electrodes via a transmastoid approach. Right ears, which served as
      controls, were not surgically manipulated. Hearing tests were conducted before
      implantation (BI) and then 4 weeks post-implantation both without electrical
      stimulation (NS) and with electrical stimulation (S). During the latter
      condition, prosthetic electrical stimuli encoding 3 dimensions of head angular
      velocity were delivered to the 3 ampullary branches of the left vestibular nerve
      via each of 3 electrode pairs of a multichannel vestibular prosthesis. Electrical
      stimuli comprised charge-balanced biphasic pulses at a baseline rate of 94
      pulses/s, with pulse frequency modulated from 48 to 222 pulses/s by head angular
      velocity. ABR hearing thresholds to clicks and tone pips at 1, 2, and 4 kHz
      increased by 5-10 dB from BI to NS and increased another ~5 dB from NS to S in
      implanted ears. No significant change was seen in right ears. DPOAE amplitudes
      decreased by 2-14 dB from BI to NS in implanted ears. There was a slight but
      insignificant decrease of DPOAE amplitude and a corresponding increase of
      DPOAE/Noise floor ratio between NS and S in implanted ears. Vestibular prosthesis
      electrode implantation and activation have small but measurable effects on
      hearing in rhesus monkeys. Coupled with the clinical observation that patients
      with cochlear implants only rarely exhibit signs of vestibular injury or spurious
      vestibular nerve stimulation, these results suggest that although implantation
      and activation of multichannel vestibular prosthesis electrodes in human will
      carry a risk of hearing loss, that loss is not likely to be severe.

PMID- 21195756
TI  - Anti-inflammatory activity of Sorbus commixta water extract and its molecular
      inhibitory mechanism.
AB  - ETHNOPHARMACOLOGICAL SIGNIFICANCE: Sorbus commixta Hedl. (Rosaceae) is a well
      known traditionally valuable medicinal plant in Korea, China and Japan. This
      plant has been prescribed for long time for various inflammatory symptoms such as
      asthma, bronchitis, gastritis and dropsy. AIM OF STUDY: Although a number of
      pharmacological properties have already been demonstrated, the anti-inflammatory
      effect of this plant and its associated molecular mechanisms has not yet been
      fully investigated. MATERIALS AND METHODS: In order to address the anti
      inflammatory activity of S. commixta water extract (Sc-WE), lipopolysaccharide
      (LPS)-stimulated macrophages were employed and production of inflammatory
      mediators by these cells were evaluated. RESULTS: Sc-WE significantly suppressed
      the production of nitric oxide (NO) and prostaglandin (PG)E(2) in a dose
      dependent manner and blocked ear edema formation induced by arachidonic acid in
      mouse. In addition, this extract effectively diminished the mRNA levels of
      inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, indicating that the
      inhibition occurs at the transcriptional level. Interestingly, Sc-WE remarkably
      blocked NF-kappaB translocation and its upstream signaling events by inhibition
      of kappaBalpha (IkappaBalpha), IkappaBalpha kinase (IKK), Akt (protein kinase B),
      phosphoinositide-dependent kinase 1 (PDK1), p85/phosphoinositide-3-kinase (PI3K),
      as per the results obtained from the reporter gene assay and immunoblotting
      analysis. More intriguingly, Sc-WE suppressed activities of Src and Syk kinases
      as well as their phosphorylation levels without altering molecular complex
      formation between them and toll like receptor (TLR)4 or MyD88, an adaptor protein
      of TLR4-mediated signaling. CONCLUSION: Therefore, our results suggest that Sc-WE
      can be developed as a potent anti-inflammatory remedy, acting by suppressing the
      inflammatory signaling cascade composed of Src, Syk, and NF-kappaB.

PMID- 21195757
TI  - Hypophosphorylated and inactive Pyk2 associates with paxillin at the microtubule
      organizing center in hematopoietic cells.
AB  - Pyk2 is a non-receptor tyrosine kinase that regulates cellular adhesion. We
      generated antibodies to a peptide corresponding to the N-terminus (NT) of Pyk2
      and another to a portion of the C-terminal (CT) domain. Only the CT antiserum
      recovered paxillin-associated Pyk2. These antibodies recognized overlapping but
      biochemically distinct molecular species of Pyk2 since the CT antiserum recovered
      Pyk2 after NT antibody immunodepletion. Furthermore, the CT antibody could not
      immunoblot NT antibody-captured Pyk2. Phosphorylation partially accounts for the
      differential binding of these antibodies as dephosphorylation of Pyk2 recovered
      with the NT antibodies allows for recognition by the CT antibody. Additionally,
      Pyk2 recovered with the NT antibody displays increased serine/threonine
      phosphorylation. We suggest that the NT epitope is inaccessible to the antibody
      because Pyk2 is in a closed confirmation in association with paxillin. Upon
      induction of serine and/or threonine phosphorylation of Pyk2, it opens to a
      confirmation that allows for antibody binding to the NT epitope but at the same
      time no longer binds paxillin or the CT antiserum. These antibodies also display
      differential staining of Pyk2 in both T cells and macrophages. Pyk2 recognized by
      the CT antibody, but not the NT antibody, colocalized with paxillin at the
      microtubule-organizing center (MTOC). The MTOC-bound Pyk2 was not tyrosine
      phosphorylated upon T cell activation. We hypothesize that a reservoir of
      primarily inactive Pyk2 associates with paxillin at the MTOC, which may allow for
      rapid delivery of Pyk2 to specific sites of adhesion.

PMID- 21195758
TI  - EGF-like peptide-enhanced cell motility in Dictyostelium functions independently
      of the cAMP-mediated pathway and requires active Ca2+/calmodulin signaling.
AB  - Current knowledge suggests that cell movement in the eukaryotic slime mold
      Dictyostelium discoideum is mediated by different signaling pathways involving a
      number of redundant components. Our previous research has identified a specific
      motility-enhancing function for epidermal growth factor-like (EGFL) repeats in
      Dictyostelium, specifically for the EGFL repeats of cyrA, a matricellular,
      calmodulin (CaM)-binding protein in Dictyostelium. Using mutants of cAMP
      signaling (carA(-), carC(-), gpaB(-), gpbA(-)), the endogenous calcium (Ca(2+))
      release inhibitor TMB-8, the CaM antagonist W-7, and a radial motility bioassay,
      we show that DdEGFL1, a synthetic peptide whose sequence is obtained from the
      first EGFL repeat of cyrA, functions independently of the cAMP-mediated signaling
      pathways to enhance cell motility through a mechanism involving Ca(2+) signaling,
      CaM, and RasG. We show that DdEGFL1 increases the amounts of polymeric myosin II
      heavy chain and actin in the cytoskeleton by 24.1+/-10.7% and 25.9+/-2.1%
      respectively and demonstrate a link between Ca(2+)/CaM signaling and cytoskeletal
      dynamics. Finally, our findings suggest that carA and carC mediate a brake
      mechanism during chemotaxis since DdEGFL1 enhanced the movement of carA(-)/carC(
      ) cells by 844+/-136% compared to only 106+/-6% for parental DH1 cells. Based on
      our data, this signaling pathway also appears to involve the G-protein beta
      subunit, RasC, RasGEFA, and protein kinase B. Together, our research provides
      insight into the functionality of EGFL repeats in Dictyostelium and the signaling
      pathways regulating cell movement in this model organism. It also identifies
      several mechanistic components of DdEGFL1-enhanced cell movement, which may
      ultimately provide a model system for understanding EGFL repeat function in
      higher organisms.

PMID- 21195759
TI  - Particle size-dependent and surface charge-dependent biodistribution of gold
      nanoparticles after intravenous administration.
AB  - Gold nanoparticles (GNP) provide many opportunities in imaging, diagnostics, and
      therapies of nanomedicine. Hence, their biokinetics in the body are prerequisites
      for specific tailoring of nanomedicinal applications and for a comprehensive risk
      assessment. We administered (198)Au-radio-labelled monodisperse, negatively
      charged GNP of five different sizes (1.4, 5, 18, 80, and 200 nm) and 2.8 nm GNP
      with opposite surface charges by intravenous injection into rats. After 24h, the
      biodistribution of the GNP was quantitatively measured by gamma-spectrometry. The
      size and surface charge of GNP strongly determine the biodistribution. Most GNP
      accumulated in the liver increased from 50% of 1.4 nm GNP to >99% of 200 nm GNP.
      In contrast, there was little size-dependent accumulation of 18-200 nm GNP in
      most other organs. However, for GNP between 1.4 nm and 5 nm, the accumulation
      increased sharply with decreasing size; i.e. a linear increase with the
      volumetric specific surface area. The differently charged 2.8 nm GNP led to
      significantly different accumulations in several organs. We conclude that the
      alterations of accumulation in the various organs and tissues, depending on GNP
      size and surface charge, are mediated by dynamic protein binding and exchange. A
      better understanding of these mechanisms will improve drug delivery and dose
      estimates used in risk assessment.

PMID- 21195760
TI  - A novel approach to identify non-palpable breast lesions combining fluorescent
      liposomes and magnetic resonance-guided high intensity focused ultrasound
      triggered release.
AB  - The combination of fluorescein-containing liposomes (FCL) and magnetic resonance
      guided high intensity focused ultrasound (MR-HIFU)-triggered release is a
      promising approach for lesion demarcation and more efficient removal of non
      palpable breast lesions. Exposure of FCL to ablation temperatures (60  degrees C)
      using MR-HIFU would result in palpable, stained tumors, which are more easy to
      identify during surgical resection. In this study, proof-of-concept concerning
      fluorescent FCL for MR-HIFU-triggered release and tumor demarcation of non
      palpable breast lesions is presented. Ex vivo experiments in human blood and
      porcine muscle tissue showed increased label release from the liposomes, clear
      fluorescence enhancement and diffusion of the released compound after heating to
      60  degrees C. Next, fluorescein release of FCL was observed after MR-HIFU
      mediated mild hyperthermia (42  degrees C) and ablation temperature (60  degrees
      C) for a short period (30s), which is in line with the clinically relevant MR
      HIFU treatment parameters. These results indicate the potential of the FCL as a
      tool to improve tumor demarcation in patients by MR-HIFU-triggered release.
      Therefore, this method may offer a new tool for efficient surgical resection of
      non-palpable breast tumor lesions by enabling proper discrimination between tumor
      tissue and adjacent healthy tissue.

PMID- 21195761
TI  - The influence of pulmonary surfactant on nanoparticulate drug delivery systems.
AB  - The pulmonary route is very attractive for drug delivery by inhalation. In this
      regard, nanoparticulate drug delivery systems, designed as multifunctional
      engineered nanoparticles, are very promising since they combine several
      opportunities like a rather uniform distribution of drug dose among all
      ventilated alveoli allowing for uniform cellular drug internalization. However,
      although the field of nanomedicine offers multiple opportunities, it still is in
      its infancy and the research has to proceed in order to obtain a specific
      targeting of the drug combined with minimum side effects. If inhaled
      nanoparticulate drug delivery systems are deposited on the pulmonary surfactant,
      they come into contact with phospholipids and surfactant proteins. It is highly
      likely that the interaction of nanoparticulate drug delivery systems with
      surfactant phospholipids and proteins will be able to mediate/modulate the
      further fate of this specific drug delivery system. In the present comment, we
      discuss the potential interactions of nanoparticulate drug delivery systems with
      pulmonary surfactant as well as the potential consequences of this interaction.

PMID- 21195762
TI  - A shotgun proteomic study of the protein corona associated with cholesterol and
      atheronal-B surface-modified quantum dots.
AB  - As part of ongoing research in our group, we are keen to monitor the protein
      binding and movement of sterols and oxysterols in biological systems in real
      time. However, prior to performing these in vivo studies, we have herein studied
      how sterol and oxysterol surface modification of quantum dots affects their
      associated protein coronas. Thus, we have synthesized and analyzed cholesterol
      and atheronal-B surface-modified quantum dots (termed QD-chol and QD-ath-B,
      respectively). The fluorescence properties and aggregation propensities of QD
      chol and QD-ath-B are unchanged relative to amino-functionalized quantum dots (QD
      NH(2)) in aqueous buffers. Shotgun proteomic analyses of the protein coronas
      reveal that QD-ath-B and QD-chol are bound significantly higher to LDL, vLDL and
      HDL particles than QD-NH(2). Thus, almost all the component proteins of the HDL
      and LDL proteomes are elevated in the protein coronas around the QD-chol and QD
      ath-B nanomaterials. In addition, the reduced positive surface charge of the QD
      chol and QD-ath-B materials, relative to QD-NH(2), means that hydrophobic
      antibody light chain fragments and beta-2-glycoprotein (apo H) bind them
      preferentially to QD-NH(2).

PMID- 21195763
TI  - Juvenile hormone synthesis: "esterify then epoxidize" or "epoxidize then
      esterify"? Insights from the structural characterization of juvenile hormone acid
      methyltransferase.
AB  - Juvenile hormones (JHs) play key roles in regulating metamorphosis and
      reproduction in insects. The last two steps of JH synthesis diverge depending on
      the insect order. In Lepidoptera, epoxidation by a P450 monooxygenase precedes
      esterification by a juvenile hormone acid methyltransferase (JHAMT). In
      Orthoptera, Dictyoptera, Coleoptera and Diptera epoxidation follows methylation.
      The aim of our study was to gain insight into the structural basis of JHAMT's
      substrate recognition as a means to understand the divergence of these pathways.
      Homology modeling was used to build the structure of Aedes aegypti JHAMT. The
      substrate binding site was identified, as well as the residues that interact with
      the methyl donor (S-adenosylmethionine) and the carboxylic acid of the substrate
      methyl acceptors, farnesoic acid (FA) and juvenile hormone acid (JHA). To gain
      further insight we generated the structures of Anopheles gambiae, Bombyx mori,
      Drosophila melanogaster and Tribolium castaneum JHAMTs. The modeling results were
      compared with previous experimental studies using recombinant proteins, whole
      insects, corpora allata or tissue extracts. The computational study helps explain
      the selectivity toward the (10R)-JHA isomer and the reduced activity for palmitic
      and lauric acids. The analysis of our results supports the hypothesis that all
      insect JHAMTs are able to recognize both FA and JHA as substrates. Therefore, the
      order of the methylation/epoxidation reactions may be primarily imposed by the
      epoxidase's substrate specificity. In Lepidoptera, epoxidase might have higher
      affinity than JHAMT for FA, so epoxidation precedes methylation, while in most
      other insects there is no epoxidation of FA, but esterification of FA to form MF,
      followed by epoxidation to JH III.

PMID- 21195764
TI  - Cre recombinase resources for conditional mouse mutagenesis.
AB  - Large scale international activities for systematic conditional mouse
      mutagenesis, exploiting advances in the sophisticated manipulation of the mouse
      genome, has established the mouse as the premier organism for developing models
      of human disease and drug action. Conditional mutagenesis is critical for the
      elucidation of the gene functions that exert pleiotropic effects in a variety of
      cell types and tissues throughout the life of the animal. The majority of new
      mouse mutants are therefore designed as conditional, activated only in a specific
      tissue (spatial control) and/or life stage (temporal control) through biogenic
      Cre/loxP technologies. The full power of conditional mutant mice can therefore
      only be exploited with the availability of well characterized mouse lines
      expressing Cre-recombinase in tissue, organ and cell type-specific patterns, to
      allow the creation of somatic mutations in defined genes. This chapter provides
      an update on the current state of Cre driver mouse lines worldwide, and reviews
      the available public databases and portals that capture critical details of Cre
      driver lines such as the efficiency of recombination, cell tissue specificity, or
      genetic background effects. The continuously changing landscape of these mouse
      resources reflects the rapid progression of research and development in
      conditional and inducible mouse mutagenesis.

PMID- 21195765
TI  - Recombineering, transfection, Western, IP and ChIP methods for protein tagging
      via gene targeting or BAC transgenesis.
AB  - Protein tagging offers many advantages for proteomic and regulomic research.
      Ideally, protein tagging is equivalent to having a high affinity antibody for
      every chosen protein. However, these advantages are compromised if the tagged
      protein is overexpressed, which is usually the case from cDNA expression vectors.
      Physiological expression of tagged proteins can be achieved by gene targeting to
      knock-in the protein tag or by BAC transgenesis. BAC transgenes usually retain
      the native gene architecture including all cis-regulatory elements as well as the
      exon-intron configurations. Consequently most BAC transgenes are authentically
      regulated (e.g. by transcription factors, cell cycle, miRNA) and can be
      alternatively spliced. Recombineering has become the method of choice for
      generating targeting constructs or modifying BACs. Here we present methods with
      detailed protocols for protein tagging by recombineering for BAC transgenesis
      and/or gene targeting, including the evaluation of tagged protein expression, the
      retrieval of associated protein complexes for mass spectrometry and the use of
      the tags in ChIP (chromatin immunoprecipitation).

PMID- 21195766
TI  - Caenorhabditis elegans as a model system for identifying effectors of alpha
      synuclein misfolding and dopaminergic cell death associated with Parkinson's
      disease.
AB  - Protein misfolding and aggregation are key pathological features observed in
      numerous neurodegenerative diseases, including the misfolding of alpha-synuclein
      (alpha-syn) in Parkinson's disease (PD) and beta-amyloid in Alzheimer's disease.
      While this phenomenon is widely observed, the etiology and progression of these
      diseases is not fully understood. Furthermore, there is a lack of therapeutic
      treatments directed at halting the progression and neurodegeneration associated
      with these diseases. This demands a need for an inexpensive, easy to manipulate
      multicellular organism to conduct both genetic and chemical screens within to
      identify factors that may play a pivotal role in the pathology of these diseases.
      Herein, we describe methodology involved in identifying genetic modifiers of
      alpha-syn misfolding and toxicity in the nematode roundworm, Caenorhabditis
      elegans. Transgenic nematodes engineered to express human alpha-syn in the body
      wall muscles or dopaminergic (DA) neurons result in formation of cytoplasmic
      puncta or DA neurodegeneration, respectively. Using these models, we describe the
      use of RNA interference (RNAi) and transgenic gene expression to functionally
      elucidate potential therapeutic gene targets that alter alpha-syn misfolding and
      DA neurotoxicity.

PMID- 21195767
TI  - Structural characterization and anti-HIV-1 activities of arginine/glutamate-rich
      polypeptide Luffin P1 from the seeds of sponge gourd (Luffa cylindrica).
AB  - Luffin P1, the smallest ribosome-inactivating peptide from the seeds of Luffa
      cylindrica was found to have anti-HIV-1 activity in HIV-1 infected C8166 T-cell
      lines and be able to bind with HIV Rev Response Element. Nuclear magnetic
      resonance spectroscopy revealed that the Luffin P1 comprises a helix-loop-helix
      motif, with the two alpha helices tightly associated by two disulfide bonds.
      Based on our findings, we conclude that unlike the well-studied ribosome
      inactivating proteins, which exert their action through N-glycosidase activities,
      Luffin P1 demonstrates a novel inactivation mechanism probably through the charge
      complementation with viral or cellular proteins. Our work also provides a new
      scaffold for the design of novel inhibitors from a simple helical motif.

PMID- 21195768
TI  - F-type lectin involved in defense against bacterial infection in the pearl oyster
      (Pinctada martensii).
AB  - In invertebrates and vertebrates, carbohydrate-binding proteins (lectins) play an
      important role in innate immunity against microbial invasion. In the present
      study, we report the cloning of an F-type lectin (designated as PmF-lectin) from
      pearl oyster (Pinctada martensii) using a combination of expression sequence tag
      (EST) analysis and rapid amplification of cDNA ends (RACE) PCR. The full-length
      cDNA of PmF-lectin contains an open reading frame (ORF) of 579 bp coding for192
      amino acids. The deduced polypeptide possesses six conserved residues of the F
      lectin family critical for the formation of disulfide bonds (Cys43-Cys143, Cys75
      Cys76 and Cys102-Cys119). Reverse transcription PCR (RT-PCR) and real-time
      quantitative PCR (qRT-PCR) analyses in adult tissues showed that the PmF-lectin
      mRNA was abundantly expressed in haemocytes and gill, moderately expressed in the
      mantle, and rarely expressed in other tissues tested. After challenge with Vibrio
      alginolyticus, expression of PmF-lectin mRNA in haemocytes was dramatically up
      regulated, reaching the highest level (13-fold higher than that of the control
      group) at 3 h post challenge, and then dropped gradually. These results suggest
      that PmF-lectin is a member of the F-lectin family and is involved in the innate
      immune response in pearl oyster.

PMID- 21195769
TI  - Vibriosis induced by experimental cohabitation in Crassostrea gigas: evidence of
      early infection and down-expression of immune-related genes.
AB  - The understanding of reciprocal interactions between Crassostrea gigas and Vibrio
      sp., whether these be virulent or avirulent, is vital for the development of
      methods to improve the health status of cultured oysters. We describe an original
      non-invasive experimental infection technique using cohabitation, designed to
      explore these interactions. Using real-time PCR techniques we examined the
      dynamics of virulent and avirulent Vibrio sp. in oyster hemolymph and tank
      seawater, and made a parallel study of the expression of four genes involved in
      oyster immune defense: Cg-BPI, Cg-EcSOD, Cg-IkappaB, Cg-TIMP. No mortality
      occurred in control animals, but oysters put in cohabitation for 2-48 h with
      animals previously infected by two Vibrio pathogens suffered mortalities from 2
      to 16 days post-cohabitation. Our results show that virulent Vibrio infect
      healthy individuals after only 2 h of cohabitation, with values ranging from 4.5
      x 102 to 2 x 104 cells ml-1 hemolymph. Simultaneously, an approximate ten-fold
      increase of the total Vibrio population was observed in control animals, with a
      6.6-78.5-fold up-expression of targeted genes. In contrast, oysters exposed to
      harmful bacteria had mean expression levels strongly down-regulated by a factor
      of 9.2-29 (depending on the gene) compared with control animals. Although oysters
      were still found to be infected by virulent Vibrio after 6-48 h of cohabitation,
      no significant differences were noted when comparing levels of each transcript in
      control and infected oysters at the same sampling times during this period: the
      important differences were noted before 6 h cohabitation. Taken together, our
      data support (1) the hypothesis that virulent Vibrio disturbs the immune response
      of this invertebrate host both rapidly and significantly, although this occurs
      specifically during an early and transient period during the first 6 h of
      cohabitation challenge, and that (2) expression of targeted genes is not
      correlated with vibriosis resistance.

PMID- 21195770
TI  - Molecular characterization and expression analysis of Cathepsin B and L cysteine
      proteases from rock bream (Oplegnathus fasciatus).
AB  - Cathepsins are lysosomal cysteine proteases of the papain family that play an
      important role in intracellular protein degradation and turn over within the
      lysosomal system. In the present study, full-length sequences of cathepsin B
      (RbCathepsin B) and L (RbCathepsin L) were identified after transcriptome
      sequencing of rock bream Oplegnathus fasciatus mixed tissue cDNA. Cathepsin B was
      composed of 330 amino acid residues with 36 kDa predicted molecular mass.
      RbCathepsin L contained 336 amino acid residues encoding for a 38 kDa predicted
      molecular mass protein. The sequencing analysis results showed that both
      cathepsin B and L contain the characteristic papain family cysteine protease
      signature and active sites for the eukaryotic thiol proteases of cysteine,
      asparagine and histidine. In addition, RbCathepsin L contained EF hand Ca(2+)
      binding and cathepsin propeptide inhibitor domains. The rock bream cathepsin B
      and L showed the highest amino acid identity of 90 and 95% to Lutjanus
      argentimaculatus cathepsin B and Lates calcarifer cathepsin L, respectively. By
      phylogenetic analysis, cathepsin B and L exhibited a high degree of evolutionary
      relationship to respective cathepsin family members of the papain superfamily.
      Quantitative real-time RT-PCR analysis results confirmed that the expression of
      cathepsin B and L genes was constitutive in all examined tissues isolated from un
      induced rock bream. Moreover, activation of RbCathepsin B and L mRNA was observed
      in both lipopolysaccharide (LPS) and Edwardsiella tarda challenged liver and
      blood cells, indicating a role of immune response in rock bream.

PMID- 21195771
TI  - Reduced gut bacterial translocation in European sea bass (Dicentrarchus labrax)
      fed mannan oligosaccharides (MOS).
AB  - The objective of this study was to determine the effect of mannan
      oligosaccharides derived from the outer cell wall of a select strain of
      Saccharomyces cerevisiae (Bio-Mos, Alltech Inc, USA) on mucus production,
      selected mucus immune parameters activity, gut morphology and in vivo and ex vivo
      gut bacterial translocation for European sea bass (Dicentrarchus labrax).
      Specimens were fed 4 g kg-1 dietary MOS level of inclusion in a commercial sea
      bass diet for eight weeks. At the end of this period, anterior gut mucosal folds
      height, width and folds surface area were increased by MOS supplementation (P <
      0.05, n = 240). Posterior gut presented shorter folds (P < 0.05, n = 240) but
      wider that those fed control diet (P < 0.05, n = 240) resulting in increased
      total surface area (P < 0.05, n = 240). For rectum, feeding MOS reduced fold
      length (P < 0.05, n = 240). Gut morphological analyses showed an enhancement in
      the number of cells secreting acid mucins by area unit, higher density of
      eosinophilic granulocytes (ECGs) in the mucosa for fish fed MOS together with an
      improvement in gut mucus lysozyme activity which could be related to the reduced
      in vivo and ex vivo gut bacterial translocation found. No differences were found
      for the skin mucus immune parameters evaluated.

PMID- 21195772
TI  - Gut SCP is an immune-relevant molecule involved in the primary immunological
      memory or pattern recognition in the amphioxus Branchiostoma belcheri.
AB  - To understand the role of calcium-binding proteins of invertebrates in
      immunological response, amphioxus sarcoplasmic calcium-binding protein (SCP) was
      investigated in the present study. Following gene cloning, recombinant protein
      expression and purification and antibody preparation, the expression and
      alteration of SCP in the response to bacterial challenge were detected using
      Western blotting. SCP was not detected in the branchia, humoral fluid, gonad or
      in the gut of wounded animals, but it was abundant in muscle and appeared in the
      gut of healthy animals using Vibrio parahaemolyticus immunization and challenge.
      Furthermore, whether gut SCP possessed anamnestic response was investigated using
      cross-immune challenge between Gram-positive and -negative bacteria. Gut SCP
      showed stronger anamnestic activity or pattern-recognition in response to Gram
      negative bacterium V. parahaemolyticus than Gram-positive bacterium
      Staphylococcus aureus. The response was faster and more species-specific to V.
      parahaemolyticus, whereas it was slower and longer to S. aureus. The reason why
      the response showed significant difference between Gram-positive and -negative
      bacteria awaits investigation. These results indicate that gut SCP is an immune
      relevant molecule involved in the primary immunological memory or pattern
      recognition in the amphioxus Branchiostoma belcheri.

PMID- 21195773
TI  - A Crassostrea gigas Toll-like receptor and comparative analysis of TLR pathway in
      invertebrates.
AB  - Toll-like receptor (TLR) signaling pathway was an important and evolutionarily
      conserved innate immune pathway. Evolutionary lineage of this pathway in the
      Lophotrochozoans is still less understood. In this study, we cloned a novel TLR,
      a key component of TLR pathway, from Crassostrea gigas, and named it CgToll-1.
      The 4343 base pairs full-length cDNA was assembled with the 3' and 5' RACE (rapid
      amplification of cDNA ends) PCR results, and containing a 3540 bp open reading
      frame, which encoding a putative TLR protein of 1179 amino acid residues. Real
      time reverse transcription polymerase chain reaction analysis revealed that the
      highest CgToll-1 expression level was in hemolymph, and the expression pattern in
      hemolymph dramatically increased in the presence of bacteria Vibrio anguillarum.
      Furthermore, TLR pathway core genes of mollusks were searched and compared with
      model invertebrates. Phylogenetic trees of two downstream genes (IkappaB, Rel)
      showed that mollusks genes were closer to Drosophila melanogaster than
      Strongylocentrotus purpuratus, while three upstream genes (MyD88, IRAK, TRAF6)
      showed the opposite propensity. We have also detected that these two downstream
      genes were significantly more conservative than the three upstream genes based on
      amino acid sequence alignment. We found no significant difference between the
      codon usage biases of TLR pathway genes. This study suggests that CgToll-1 was a
      constitutive and inducible protein and thus could play an important role in the
      immune responses against bacterium infection. Besides, comparative analysis of
      TLR pathway showed that gene loss and divergence might exist during evolution in
      invertebrate.

PMID- 21195774
TI  - Error-related medial frontal theta activity predicts cingulate-related structural
      connectivity.
AB  - Studies on electrophysiological signatures of error processing have focused on
      the medial frontal cortex, although widespread neuroanatomical networks support
      error/action monitoring. Here, electrophysiological responses to errors were
      combined with structural white matter diffusion tensor imaging (DTI) to
      investigate the long-range anatomical networks that support error processing. The
      approach taken here was to link individual differences in error-related EEG
      responses to individual differences in white matter connectional anatomy. Twenty
      subjects performed a speeded instructed choice task (a variant of the Simon task)
      designed to elicit response errors, and also underwent DTI scanning in a separate
      session. In the EEG data, significantly enhanced theta (4-8 Hz) oscillations were
      observed over medial frontal electrodes (centered on FCz) during response errors.
      Mid-frontal scalp sites (likely reflecting medial frontal cortex activity) also
      functioned as a strong "hub" for information flow, measured through theta-band
      phase synchronization degree. Next, a dipole source of the error-related theta
      band activity was localized for each subject, accounting for approximately 80% of
      the topographical variance. Correlating individual differences in medial frontal
      theta dynamics with white matter tracts linking these dipole sources to the rest
      of the brain revealed that subjects with stronger error-related theta also had
      stronger white matter connectivity with the ventral striatum and inferior frontal
      gyrus. Further, subjects in whom medial frontal regions acted as a stronger
      synchronization "hub" had stronger connectivity between the dipole source
      location and the corpus callosum and dorsomedial prefrontal white matter
      pathways. These findings provide novel evidence for the role of widespread fronto
      striatal networks in monitoring actions and signaling behavioral errors.

PMID- 21195776
TI  - Semi-supervised pattern classification of medical images: application to mild
      cognitive impairment (MCI).
AB  - Many progressive disorders are characterized by unclear or transient diagnoses
      for specific subgroups of patients. Commonly used supervised pattern recognition
      methodology may not be the most suitable approach to deriving image-based
      biomarkers in such cases, as it relies on the availability of categorically
      labeled data (e.g., patients and controls). In this paper, we explore the
      potential of semi-supervised pattern classification to provide image-based
      biomarkers in the absence of precise diagnostic information for some individuals.
      We employ semi-supervised support vector machines (SVM) and apply them to the
      problem of classifying MR brain images of patients with uncertain diagnoses. We
      examine patterns in serial scans of ADNI participants with mild cognitive
      impairment (MCI), and propose that in the absence of sufficient follow-up
      evaluations of individuals with MCI, semi-supervised strategy is potentially more
      appropriate than the fully-supervised paradigm employed up to date.

PMID- 21195777
TI  - Segmentation of fiber tracts based on an accuracy analysis on diffusion tensor
      software phantoms.
AB  - Due to its unique sensitivity to tissue microstructure, one of the primary
      applications of diffusion-weighted magnetic resonance imaging is the
      reconstruction of neural fiber pathways by means of fiber-tracking algorithms. In
      this work, we make use of realistic diffusion-tensor software phantoms in order
      to carry out an analysis of the precision of streamline tractography by
      systematically varying certain properties of the simulated image data (noise,
      tensor anisotropy, and image resolution) as well as certain fiber-tracking
      parameters (number of seed points and step length). Building upon the gained
      knowledge about the precision of the analyzed fiber-tracking algorithm, we
      proceed by suggesting a fuzzy segmentation algorithm for diffusion tensor images
      which better estimates the precise spatial extent of a tracked fiber bundle. The
      presented segmentation algorithm utilizes information given by the estimated main
      diffusion direction in a voxel and the respective uncertainty, and its validity
      is confirmed by both qualitative and quantitative analyses.

PMID- 21195775
TI  - Antemortem differential diagnosis of dementia pathology using structural MRI:
      Differential-STAND.
AB  - The common neurodegenerative pathologies underlying dementia are Alzheimer's
      disease (AD), Lewy body disease (LBD) and frontotemporal lobar degeneration
      (FTLD). Our aim was to identify patterns of atrophy unique to each of these
      diseases using antemortem structural MRI scans of pathologically confirmed
      dementia cases and build an MRI-based differential diagnosis system. Our approach
      of creating atrophy maps using structural MRI and applying them for
      classification of new incoming patients is labeled Differential-STAND
      (Differential Diagnosis Based on Structural Abnormality in Neurodegeneration).
      Pathologically confirmed subjects with a single dementing pathologic diagnosis
      who had an MRI at the time of clinical diagnosis of dementia were identified: 48
      AD, 20 LBD, 47 FTLD-TDP (pathology-confirmed FTLD with TDP-43). Gray matter
      density in 91 regions-of-interest was measured in each subject and adjusted for
      head size and age using a database of 120 cognitively normal elderly. The atrophy
      patterns in each dementia type when compared to pathologically confirmed controls
      mirrored known disease-specific anatomic patterns: AD-temporoparietal association
      cortices and medial temporal lobe; FTLD-TDP-frontal and temporal lobes and LBD
      bilateral amygdalae, dorsal midbrain and inferior temporal lobes. Differential
      STAND based classification of each case was done based on a mixture model
      generated using bisecting k-means clustering of the information from the MRI
      scans. Leave-one-out classification showed reasonable performance compared to the
      autopsy gold standard and clinical diagnosis: AD (sensitivity: 90.7%;
      specificity: 84%), LBD (sensitivity: 78.6%; specificity: 98.8%) and FTLD-TDP
      (sensitivity: 84.4%; specificity: 93.8%). The proposed approach establishes a
      direct a priori relationship between specific topographic patterns on MRI and
      "gold standard" of pathology which can then be used to predict underlying
      dementia pathology in new incoming patients.

PMID- 21195778
TI  - Novel Fast Marching for Automated Segmentation of the Hippocampus (FMASH): method
      and validation on clinical data.
AB  - With hippocampal atrophy both a clinical biomarker for early Alzheimer's Disease
      (AD) and implicated in many other neurological and psychiatric diseases, there is
      much interest in the accurate, reproducible delineation of this region of
      interest (ROI) in structural MR images. Here we present Fast Marching for
      Automated Segmentation of the Hippocampus (FMASH): a novel approach using the
      Sethian Fast Marching (FM) technique to grow a hippocampal ROI from an
      automatically-defined seed point. Segmentation performance is assessed on two
      separate clinical datasets, utilising expert manual labels as gold standard to
      quantify Dice coefficients, false positive rates (FPR) and false negative rates
      (FNR). The first clinical dataset (denoted CMA) contains normal controls (NC) and
      atrophied AD patients, whilst the second is a collection of NC and bipolar (BP)
      patients (denoted BPSA). An optimal and robust stopping criterion is established
      for the propagating FM front and the final FMASH segmentation estimates compared
      to two commonly-used methods: FIRST/FSL and Freesurfer (FS). Results show that
      FMASH outperforms both FIRST and FS on the BPSA data, with significantly higher
      Dice coefficients (0.80+/-0.01) and lower FPR. Despite some intrinsic bias for
      FIRST and FS on the CMA data, due to their training, FMASH performs comparably
      well on the CMA data, with an average bilateral Dice coefficient of 0.82+/-0.01.
      Furthermore, FMASH most accurately captures the hippocampal volume difference
      between NC and AD, and provides a more accurate estimation of the problematic
      hippocampus-amygdala border on both clinical datasets. The consistency in
      performance across the two datasets suggests that FMASH is applicable to a range
      of clinical data with differing image quality and demographics.

PMID- 21195779
TI  - Intermittent spike-wave dynamics in a heterogeneous, spatially extended neural
      mass model.
AB  - Generalised epileptic seizures are frequently accompanied by sudden, reversible
      transitions from low amplitude, irregular background activity to high amplitude,
      regular spike-wave discharges (SWD) in the EEG. The underlying mechanisms
      responsible for SWD generation and for the apparently spontaneous transitions to
      SWD and back again are still not fully understood. Specifically, the role of
      spatial cortico-cortical interactions in ictogenesis is not well studied. We
      present a macroscopic, neural mass model of a cortical column which includes two
      distinct time scales of inhibition. This model can produce both an oscillatory
      background and a pathological SWD rhythm. We demonstrate that coupling two of
      these cortical columns can lead to a bistability between out-of-phase, low
      amplitude background dynamics and in-phase, high amplitude SWD activity. Stimuli
      can cause state-dependent transitions from background into SWD. In an extended
      local area of cortex, spatial heterogeneities in a model parameter can lead to
      spontaneous reversible transitions from a desynchronised background to
      synchronous SWD due to intermittency. The deterministic model is therefore
      capable of producing absence seizure-like events without any time dependent
      adjustment of model parameters. The emergence of such mechanisms due to spatial
      coupling demonstrates the importance of spatial interactions in modelling ictal
      dynamics, and in the study of ictogenesis.

PMID- 21195780
TI  - Brain MAPS: an automated, accurate and robust brain extraction technique using a
      template library.
AB  - Whole brain extraction is an important pre-processing step in neuroimage
      analysis. Manual or semi-automated brain delineations are labour-intensive and
      thus not desirable in large studies, meaning that automated techniques are
      preferable. The accuracy and robustness of automated methods are crucial because
      human expertise may be required to correct any suboptimal results, which can be
      very time consuming. We compared the accuracy of four automated brain extraction
      methods: Brain Extraction Tool (BET), Brain Surface Extractor (BSE), Hybrid
      Watershed Algorithm (HWA) and a Multi-Atlas Propagation and Segmentation (MAPS)
      technique we have previously developed for hippocampal segmentation. The four
      methods were applied to extract whole brains from 682 1.5T and 157 3T T(1)
      weighted MR baseline images from the Alzheimer's Disease Neuroimaging Initiative
      database. Semi-automated brain segmentations with manual editing and checking
      were used as the gold-standard to compare with the results. The median Jaccard
      index of MAPS was higher than HWA, BET and BSE in 1.5T and 3T scans (p<0.05, all
      tests), and the 1st to 99th centile range of the Jaccard index of MAPS was
      smaller than HWA, BET and BSE in 1.5T and 3T scans ( p<0.05, all tests). HWA and
      MAPS were found to be best at including all brain tissues (median false negative
      rate <=0.010% for 1.5T scans and <=0.019% for 3T scans, both methods). The median
      Jaccard index of MAPS were similar in both 1.5T and 3T scans, whereas those of
      BET, BSE and HWA were higher in 1.5T scans than 3T scans (p<0.05, all tests). We
      found that the diagnostic group had a small effect on the median Jaccard index of
      all four methods. In conclusion, MAPS had relatively high accuracy and low
      variability compared to HWA, BET and BSE in MR scans with and without atrophy.

PMID- 21195781
TI  - Early multisensory interactions affect the competition among multiple visual
      objects.
AB  - In dynamic cluttered environments, audition and vision may benefit from each
      other in determining what deserves further attention and what does not. We
      investigated the underlying neural mechanisms responsible for attentional
      guidance by audiovisual stimuli in such an environment. Event-related potentials
      (ERPs) were measured during visual search through dynamic displays consisting of
      line elements that randomly changed orientation. Search accuracy improved when a
      target orientation change was synchronized with an auditory signal as compared to
      when the auditory signal was absent or synchronized with a distractor orientation
      change. The ERP data show that behavioral benefits were related to an early
      multisensory interaction over left parieto-occipital cortex (50-60 ms post
      stimulus onset), which was followed by an early positive modulation (80-100 ms)
      over occipital and temporal areas contralateral to the audiovisual event, an
      enhanced N2pc (210-250 ms), and a contralateral negative slow wave (CNSW). The
      early multisensory interaction was correlated with behavioral search benefits,
      indicating that participants with a strong multisensory interaction benefited the
      most from the synchronized auditory signal. We suggest that an auditory signal
      enhances the neural response to a synchronized visual event, which increases the
      chances of selection in a multiple object environment.

PMID- 21195783
TI  - Modular organizations of novel cetacean papillomaviruses.
AB  - The phylogenetic position of cetacean papillomaviruses (PVs: Omikron-PVs and
      Upsilon-PVs) varies depending on the region of the genome analysed. They cluster
      together with Alpha-PVs when analysing early genes and with Xi-PVs and Phi-PVs
      when analysing late genes. We cloned and sequenced the complete genomes of five
      novel PVs, sampled from genital and oesophageal lesions of free-ranging
      cetaceans: Delphinus delphis (DdPV1), Lagenorhynchus acutus (TtPV3 variant), and
      Phocoena phocoena (PphPV1, PphPV2, and PphPV3). Using Maximum Likelihood and
      Bayesian approaches, all cetacean PVs constituted a monophyletic group with Alpha
      , Omega-, and Dyodelta-PVs as inferred from E1-E2 early genes analyses, thus
      matching the shared phenotype of mucosal tropism. However, cetacean PVs, with the
      exception of PphPV3, were the closest relatives of Xi-PVs and Phi-PVs in L2-L1
      late genes analyses, isolated from cow and goat, thus reflecting the close
      relationship between Cetacea and Artiodactyla. Our results are compatible with a
      recombination between ancestral PVs infecting the Cetartiodactyla lineage. Our
      study supports a complex evolutionary scenario with multiple driving forces for
      PV diversification, possibly including recombination and also interspecies
      transmission.

PMID- 21195782
TI  - Inter-rater reliability of manual and automated region-of-interest delineation
      for PiB PET.
AB  - A major challenge in positron emission tomography (PET) amyloid imaging studies
      of Alzheimer's disease (AD) is the reliable detection of early amyloid deposition
      in human brain. Manual region-of-interest (ROI) delineation on structural
      magnetic resonance (MR) images is generally the reference standard for the
      extraction of count-rate data from PET images, as compared to automated MR
      template(s) methods that utilize spatial normalization and a single set of ROIs.
      The goal of this work was to assess the inter-rater reliability of manual ROI
      delineation for PiB PET amyloid retention measures and the impact of CSF dilution
      correction (CSF) on this reliability for data acquired in elderly control (n=5)
      and AD (n=5) subjects. The intraclass correlation coefficient (ICC) was used to
      measure reliability. As a secondary goal, ICC scores were also computed for PiB
      outcome measures obtained by an automated MR-template ROI method and one manual
      rater; to assess the level of reliability that could be achieved using different
      processing methods. Fourteen ROIs were evaluated that included anterior cingulate
      (ACG), precuneus (PRC) and cerebellum (CER). The PiB outcome measures were the
      volume of distribution (V(T)), summed tissue uptake (SUV), and corresponding
      ratios that were computed using CER as reference (DVR and SUVR). Substantial
      reliability (ICC>=0.932) was obtained across 3 manual raters for V(T) and SUV
      measures when CSF correction was applied across all outcomes and regions and was
      similar in the absence of CSF correction. The secondary analysis revealed
      substantial reliability in primary cortical areas between the automated and
      manual SUV [ICC>=0.979 (ACG/PRC)] and SUVR [ICC>=0.977/0.952 (ACG/PRC)] outcomes.
      The current study indicates the following rank order among the various
      reliability results in primary cortical areas and cerebellum (high to low): 1)
      V(T) or SUV manual delineation, with or without CSF correction; 2) DVR or SUVR
      manual delineation, with or without CSF correction; 3) SUV automated delineation,
      with CSF correction; and 4) SUVR automated delineation, with or without CSF
      correction. The high inter-rater reliability of PiB outcome measures in primary
      cortical areas (ACG/PRC) is important as reliable methodology is needed for the
      detection of low levels of amyloid deposition on a cross-sectional basis and
      small changes in amyloid deposition on a longitudinal basis.

PMID- 21195784
TI  - No population genetic structure in a widespread aquatic songbird from the
      Neotropics.
AB  - Neotropical lowland organisms often show marked population genetic structure,
      suggesting restricted migration among populations. However, most phylogeographic
      studies have focused on species inhabiting humid forest interior. Little
      attention has been devoted to the study of species with ecologies conducive to
      dispersal, such as those of more open and variable environments associated with
      watercourses. Using mtDNA sequences, we examined patterns of genetic variation in
      a widely distributed Neotropical songbird of aquatic environments, the Yellow
      hooded Blackbird (Icteridae, Chrysomus icterocephalus). In contrast to many
      forest species, Yellow-hooded Blackbirds showed no detectable genetic structure
      across their range, which includes lowland populations on both sides of the
      Andes, much of northeastern South America, Amazonia, as well as a phenotypically
      distinct highland population in Colombia. A coalescent-based analysis of the
      species indicated that its effective population size has increased considerably,
      suggesting a range expansion. Our results support the hypothesis that species
      occurring in open habitats and tracking temporally dynamic environments should
      show increased dispersal propensities (hence gene flow) relative to species from
      closed and more stable environments. The phenotypic and behavioral variation
      among populations of our study species appears to have arisen recently and
      perhaps in the face of gene flow.

PMID- 21195785
TI  - The mitochondrial genome of Colossendeis megalonyx supports a basal position of
      Colossendeidae within the Pycnogonida.
AB  - We present the almost complete (16,007 bp) mitochondrial genome of a Colossendeis
      megalonyx specimen from the Southern Ocean and discuss gene order and tRNA
      structure in a comparative phylogenetic context. Our data suggest a basal
      position of the colossendeid lineage corroborating earlier phylogenetic studies
      but disagreeing with results of a recently published study that supported a
      highly derived sister-group relationship of Colossendeidae and Nymphonidae. Our
      results, together with BLAST searches and phylogenetic comparisons, indicate that
      the specimen presented as Colossendeis sp. in a series of recent studies had been
      misidentified. It has now been identified as a nymphonid species.

PMID- 21195786
TI  - Cerebellar dentate nuclei lesions reduce motivation in appetitive operant
      conditioning and open field exploration.
AB  - Recently identified pathways from the dentate nuclei of the cerebellum to the
      rostral cerebral cortex via the thalamus suggest a cerebellar role in frontal and
      prefrontal non-motor functioning. Disturbance of cerebellar morphology and
      connectivity, particularly involving these cerebellothalamocortical (CTC)
      projections, has been implicated in motivational and cognitive deficits. The
      current study explored the effects of CTC disruption on motivation in male Long
      Evans rats. The results of two experiments demonstrate that electrolytic lesions
      of the cerebellar dentate nuclei lower breaking points on an operant conditioning
      progressive ratio schedule and decrease open field exploration compared to sham
      controls. Changes occurred in the absence of motor impairment, assessed via lever
      pressing frequency and rotarod performance. Similar elevated plus maze
      performances between lesioned and sham animals indicated that anxiety did not
      influence task performance. Our results demonstrate hedonic and purposive
      motivational reduction and suggest a CTC role in global motivational processes.
      These implications are discussed in terms of psychiatric disorders such as
      schizophrenia and autism, in which cerebellar damage and motivational deficits
      often present concomitantly.

PMID- 21195787
TI  - The in vitro effect of manuka honeys on growth and adherence of oral bacteria.
AB  - Honey has been used since ancient times and more recently, for the healing of
      wounds and against infectious diseases. The aim of our study was to investigate
      the effect of two manuka honeys showing different potencies of their
      antibacterial activity, on potentially pathogenic oral bacteria. The
      antimicrobial activity was examined by determining the MIC and MBC using the
      macro dilution broth technique. The effect on the adherence was tested on growing
      cells of Streptococcus mutans on a glass surface and on a multi-species biofilm
      grown on saliva-coated hydroxyapatite discs. As expected, the antibacterial
      activity of manuka 1 (with higher potency of antibacterial activity) was the most
      important. The two tested honeys weakly inhibited the adherence of S.mutans cells
      to a glass surface at sub-MIC concentration. Manuka 1 showed a total inhibition
      of multi-species biofilm at the concentration of 200 MUg/ml manuka 2 inhibited
      biofilm formation weakly at the concentration of 200 MUg/ml but firmly at the
      concentration of 500 MUg/ml. Our findings suggest that manuka honeys might be
      able to reduce oral pathogens within dental plaque. These two honeys appear to be
      able to control dental biofilm deposit.

PMID- 21195788
TI  - Evaluation of the effects of the R- and S-enantiomers of salbutamol on equine
      isolated bronchi.
AB  - BACKGROUND: Equine obstructive pulmonary disease, also known as heaves or
      recurrent airway obstruction (RAO) is a common equine pulmonary disease with some
      similarities to human asthma and COPD, which represents a major cause of
      morbidity and loss of lung performance. Salbutamol has been widely used for the
      treatment of human airway diseases and has usually been prepared as the racemic
      form of the drug. However, recently the R-enantiomer of salbutamol has been
      introduced into clinical practice in the treatment of asthma in humans and this
      has been suggested to be an improvement on the racemic form of the drug;
      therefore thus the S-enantiomer has been demonstrated to have adverse effects in
      the lung and thus using the R-enantiomer may improve the therapeutic ratio.
      However, little is known about the properties of the R- and S-enantiomers of
      salbutamol in equine airways and the present study has evaluated the relaxant
      effects of racemic beta(2)-agonists in comparison with the R- and S-enantiomers
      in isolated equine isolated bronchi, as well as the bronchoprotective effects of
      these drugs on cholinergic and histaminergic pathway. METHODS: We have studied
      the effects of the R- and S-enantiomers of salbutamol on bronchi isolated from
      RAO-affected or unaffected horses. The first study assayed the relaxant effects
      of R- and S-salbutamol on isolated bronchial rings contracted with carbachol or
      histamine at a sub-maximal concentration (EC70). A second study evaluated the
      effects of R- and S-salbutamol on semi-logarithmic cumulative concentration
      response curves induced by carbachol or histamine. Specific software was used to
      calculate statistical significance and the appropriate sigmoidal curve-fitting
      model. RESULTS: Neither enantiomers of salbutamol caused a relaxant effect on the
      sub-maximal plateau contractile effects of carbachol; in fact, both R- and S
      salbutamol induced a slight, but significant contraction (P <= 0.05) compared to
      the controls. In contrast, R-salbutamol induced a significant relaxation of
      bronchi pre-contracted with histamine (RAO-unaffected: 92.06% +/- 2.00; RAO
      affected 100.20 +/- 3.99; P <= 0.01). S-salbutamol induced a weak relaxation (RAO
      unaffected: 15.81% +/- 5.65; RAO-affected 12.36 +/- 5.15) when compared to that
      induced by papaverine. The incubation with either R- or S-salbutamol shifted
      rightward (P <= 0.001) the carbachol contraction curve in RAO-unaffected bronchi,
      but not in RAO-affected bronchi, compared to control tissues. R-salbutamol
      induced a reduction in E(max) values (C: 9.07 gr +/- 0.68; R-salb.: 6.36 gr +/-
      0.21; P <= 0.01) in normal bronchi. On the contrary it reduced the histamine
      potency in RAO-affected bronchi (EC50 7.10 MUM +/- 0.35, P < 0.001). The
      incubation with S-salbutamol shifted leftward the histamine concentration curve
      in both normal bronchi (C: 7.00 MUM +/- 0.29; S-salb.: 2.25 MUM +/- 0.19; P <=
      0.001) and bronchi from RAO-affected horses (C: 2.80 MUM +/- 0.26; S-salb.: 1.50
      MUM +/- 0.80; P <= 0.05). CONCLUSION: Our studies have demonstrated that S
      salbutamol elicited a modest increase in contraction of equine airway smooth
      muscle induced by carbachol and induced a significant hyperresponsiveness to
      histamine. These results confirm the ability of the S-enantiomer of salbutamol to
      potentiate the contractile effect of certain spasmogens on airway smooth muscle.
      Such an adverse effect would be determined in the airways of horses with RAO and
      suggest that if salbutamol is to be used in the treatment of symptoms of RAO in
      horses, the R-enantiomer, rather than the racemic mixture should be considered.

PMID- 21195789
TI  - TLR agonist mediated suppression of allergic responses is associated with
      increased innate inflammation in the airways.
AB  - Toll-like receptor (TLR) mediated signaling induces pro-inflammatory responses
      and can both suppress and exacerbate allergic responses in the airways. The aim
      of our study was to directly compare the efficacy of different TLR agonists in
      inhibiting or exacerbating the development of Th2-mediated responses in the
      airways and investigate if the suppressive effects were associated with increased
      pro-inflammatory responses. Mice were immunized on day 0, 14 and 21 by
      intraperitoneal injection of ovalbumin/alum and exposed to ovalbumin aerosol on
      day 26 and 27. TLR2, TLR3, TLR4, TLR7 and TLR9 agonists (0.001, 0.01, 0.1, or 1
      mg/kg) were administered intratracheally 1 h before each allergen exposure. Both
      the TLR7 and TLR9 agonists dose dependently reduced airway eosinophilia, while
      the TLR3 agonist only reduced airway eosinophilia at a dose of 1.0 mg/kg. The
      TLR2 and TLR4 agonists potentiated eosinophilia. All TLR agonists enhanced
      neutrophil numbers at doses as low as 0.01 mg/kg, in particular TLR2 and TLR4
      agonists. TLR7 and TLR9 agonists also significantly reduced IL-4 and IL-5 levels
      and all TLR agonists, with the exception of TLR7, enhanced the amount IL-1beta,
      IL-6, and TNF-alpha detected in the whole lung lavage. Only application of TLR9
      agonist induced detectable levels of IL-10 in the lung. Suppressive effects of
      the TLR agonists were not dependent upon IFN-gamma and IL-10 or associated with
      increased numbers of Foxp3(+)CD4(+) Tr cells in the lavage fluid. Airway
      resistance was reduced significantly only when TLR7 agonist was administered.
      When applied therapeutically 2 days after allergen exposure, all TLR agonists,
      except TLR2, similarly reduced airway eosinophilia and IL-4 levels. Taken
      together our results show that TLR7 agonists had the strongest anti-asthmatic
      effects with the lowest pro-inflammatory potential, suggesting that activating
      TLR7 may have the greatest potential to treat allergic disorders in humans.

PMID- 21195790
TI  - A model to determine 3-month mortality risk in patients with acute-on-chronic
      hepatitis B liver failure.
AB  - BACKGROUND & AIMS: Liver failure has high mortality. There are accurate but
      controversial models to determine mortality of patients with acute-on-chronic
      hepatitis B liver failure (ACHBLF). We developed a logistic regression model
      (LRM) and tested its ability to predict the 3-month mortality of patients with
      ACHBLF. METHODS: The LRM was constructed using data from an internal cohort of
      242 consecutive patients with ACHBLF and was tested on an external cohort of 210
      patients with the same conditions. The receiver operating characteristic curves
      were calculated for the LRM, model of end-stage liver disease (MELD), Child-Pugh
      score (CPS), and a previously reported LRM that has not yet been validated in
      patients with ACHBLF. Predictions of 3-month mortality obtained with 4 models
      from the same datasets were compared using areas under receiver operating
      characteristic curves. RESULTS: The LRM identified 5 independent factors
      associated with survival of patients with ACHBLF: hepatic encephalopathy (odds
      ratio [OR], 2.165; 95% confidence interval [CI], 1.015-4.616), hepatorenal
      syndrome (OR, 9.767; 95% CI, 4.273-22.328), cirrhosis (OR, 2.339; 95% CI, 1.110
      4.930), hepatitis B e antigen (OR, 2.874; 95% CI, 1.376-6.003), and prothrombin
      activity/age (OR, 0.12; 95% CI, 0.037-0.395). Data from the internal and external
      cohorts indicated that the LRM had significantly greater prognostic accuracy than
      the MELD, CPS, or previous LRM. CONCLUSIONS: We developed a logistic regression
      model that predicted the 3-month mortality of patients with ACHBLF with greater
      accuracy than the MELD, CPS, or the previous LRM.

PMID- 21195791
TI  - Follow-up testing after treatment of Helicobacter pylori infections: cautions,
      caveats, and recommendations.

PMID- 21195792
TI  - Optimizing colonic preparation: the solution is becoming clearer and clearer.

PMID- 21195793
TI  - Speed kills.

PMID- 21195794
TI  - Preoperative detection of malignant transformation in a choledochal cyst.

PMID- 21195795
TI  - Endoscopic closure of colon perforation with band ligation; salvage technique
      after endoclip failure.

PMID- 21195796
TI  - Mucosal healing predicts late outcomes after the first course of corticosteroids
      for newly diagnosed ulcerative colitis.
AB  - BACKGROUND & AIMS: It is uncertain whether mucosal healing after the first course
      of corticosteroids therapy predicts outcome in patients with ulcerative colitis
      (UC). We evaluated whether early clinical and endoscopic responses to this
      therapy are associated with late outcomes in UC. METHODS: Patients with newly
      diagnosed UC who were prescribed corticosteroid therapy (n = 157) were followed
      up for 5 years. They were evaluated using clinical (Powel-Tuck [PT]) and
      endoscopic (Baron) indexes after 3 and 6 months, then every 6 months. Outcomes at
      month 3 (early response) were used to identify patients with complete (group A:
      PT, 0-1; Baron, 0), partial (group B: PT, 0-1; Baron, 1-3), or no response (group
      C: persistence of clinical and endoscopic activity). The association between
      early and late outcomes was assessed. RESULTS: After 5 years, there were
      significant differences between complete and partial responders in the rates of
      hospitalization (25% in group A vs 48.7% in group B; P = .0152; odds ratio [OR],
      2.85; 95% confidence interval [CI], 1.21-6.72), immunosuppression therapy (5% in
      group A vs 25.6% in group B; P = .0030; OR, 6.55; 95% CI, 1.67-25.67), colectomy
      (3.3% in group A vs 18.0% in group B; P = .0265; OR, 6.34; 95% CI, 1.24-32.37),
      and their combination (26.7% in group A vs 48.7% in group B; P = .0249; OR, 2.61;
      95% CI, 1.12-6.11). After multivariate analysis, lack of mucosal healing was the
      only factor associated with negative outcomes at 5 years (immunosuppressors:
      hazard risk [HR], 10.581; 95% CI, 2.193-51.039; P = .0033; hospitalization: HR,
      3.634; 95% CI, 1.556-8.485; P = .0029; colectomy: HR, 8.397; 95% CI, 1.278
      55.186; P = .0268). CONCLUSIONS: No mucosal healing after corticosteroid therapy
      is associated with a more aggressive disease course.

PMID- 21195797
TI  - Reporting of treatment effects from randomized trials: a plea for multivariable
      risk ratios.
AB  - Clinicians are typically interested in the effects of medical interventions that
      apply to individual patients. Such individual effects are conditional effects
      rather than marginal (or population averaged) effects. When considering odds
      ratios, conditional (adjusted) and marginal (crude) effects may differ, even in a
      randomized trial with perfectly balanced baseline covariates, due to non
      collapsibility of the odds ratio. Using a numerical example, we explained this
      phenomenon of non-collapsibility of the odds ratio and showed that the difference
      between conditional and marginal odds ratios depends on the strength of the
      association between a third (stratifying) variable and the outcome, as well as on
      the distribution of this stratifying variable in the trial population. Risk
      ratios are not affected by non-collapsibility and therefore, conditional and
      marginal risk ratios are the same when adjusting for well balanced baseline
      covariates in randomized trials. Reports on randomized trials should more often
      include treatment effects that are expressed as risk ratios rather than odds
      ratios. When odds ratios are used, adjustment for baseline covariates should be
      considered, also when these are well-balanced between the treatment groups.

PMID- 21195798
TI  - A critical analysis of the combined usage of protein localization prediction
      methods: Increasing the number of independent data sets can reduce the accuracy
      of predicted mitochondrial localization.
AB  - In the absence of a comprehensive experimentally derived mitochondrial proteome,
      several bioinformatic approaches have been developed to aid the identification of
      novel mitochondrial disease genes within mapped nuclear genetic loci. Often, many
      classifiers are combined to increase the sensitivity and specificity of the
      predictions. Here we show that the greatest sensitivity and specificity are
      obtained by using a combination of seven carefully selected classifiers. We also
      show that increasing the number of independent prediction methods can
      paradoxically decrease the accuracy of predicting mitochondrial localization.
      This approach will help to accelerate the identification of new mitochondrial
      disease genes by providing a principled way for the selection for combination of
      appropriate prediction methods of mitochondrial localization of proteins.

PMID- 21195799
TI  - European Union vaccine research--an overview.
AB  - Recent developments in vaccine research provide new momentum for an important
      area in health innovation. Particularly interesting are novel DNA vaccine
      approaches, many of which are already under clinical investigation. The Framework
      Programmes of the European Union play an important role in supporting
      collaborative efforts in vaccine research to develop new and better vaccines and
      bring them to the market. With a timely strategic reorientation towards a
      sustainable investment in innovation, the current seventh Framework Programme
      will help to bring large industry and small and medium-sized enterprises (SME) on
      board and foster partnership between stakeholders. As the first human DNA
      vaccines progresses through the development pipeline, more and more questions
      revolve around licensing and regulation and appropriate guidelines are being
      developed.

PMID- 21195800
TI  - Comparison of viral glycosylation using lectin blotting with Vero cell-derived
      and mouse brain-derived Japanese encephalitis vaccines.
AB  - We produced a Vero cell-derived inactivated Japanese encephalitis vaccine using a
      serum-free medium, as a substitute for the conventional mouse brain-derived
      Japanese encephalitis vaccine. The immunogenicity of this cell-derived vaccine
      was higher than that of the conventional mouse brain-derived vaccine. The results
      of a clinical study in humans also demonstrated higher immunogenicity of this
      cell-derived vaccine. No gene mutation was found in the viral structural proteins
      derived from Vero cells and mouse brain. So, we conducted a lectin blot analysis,
      assuming differing glycosylation as a cause of the higher immunogenicity in
      humans. The results demonstrated that vaccine reactivity varied with lectins,
      particularly with WGA, DBA, MAM, SSA, SBA, and GS-II. Thus, glycosylation
      differed with the vaccines, suggesting a possible cause of the differing
      immunogenicity between mice and humans.

PMID- 21195801
TI  - High antibody and cellular responses induced to HIV-1 clade C envelope following
      DNA vaccines delivered by electroporation.
AB  - BACKGROUND: Clade C is the predominant HIV-1 strain infecting people in sub
      Saharan Africa, India, and China and there is a critical need for a vaccine
      targeted to these areas. In this study we tested a DNA based vaccine that encodes
      the SIVgag, SIVpol and HIV-1 envelope clade C. METHODS: Rhesus macaques were
      immunized by electroporation with the DNA plasmid encoding optimized SIVgag,
      SIVpol and an HIV-1 env clade C with or without the adjuvant RANTES. Animals were
      monitored for immune responses and challenged following the final immunization
      with 25 animal infectious doses (AID) of SHIV-1157ipd3N4. RESULTS: We found that
      the vaccine induced high levels of antigen specific IFN-gamma producing effector
      cells and the capacity for CD4+ and CD8+ to proliferate upon antigen stimulation.
      Importantly, we found that the vaccine induced antibody titers as high as 1/4000.
      These antibodies were capable of neutralizing tier 1 HIV-1 viruses. Finally, when
      macaques were challenged with SHIV, viral loads were controlled in vaccinated
      groups. CONCLUSION: We conclude that immunization with a simian/human
      immunodeficiency virus DNA-based vaccine delivered by electroporation can induce
      cellular and humoral immune responses that are able to control viral replication.

PMID- 21195802
TI  - The effectiveness of trivalent inactivated influenza vaccine in children over six
      consecutive influenza seasons.
AB  - OBJECTIVE: To estimate the effectiveness of two doses of trivalent inactivated
      influenza vaccine (TIV) over six consecutive influenza seasons in a small
      community in Japan. PATIENTS AND METHODS: A prospective, non-randomized,
      observational study of TIV effectiveness was performed involving children aged 6
      months to 6 years accessing pediatric services in Soma and Shinchi, Japan. The
      total number of children under observation was 14,788. Each fall from 2002 to
      2007 TIV was offered to all children with an average uptake of 52.9%. Influenza
      rapid diagnostic tests were performed to all children with respiratory symptoms
      and a temperature >38 degrees C during each surveillance period. The efficacy of
      two doses of TIV was estimated by the relative risk of influenza illness and
      influenza associated hospitalizations and effectiveness by reduction in all
      respiratory illness in vaccinated and unvaccinated children. RESULTS: Influenza A
      occurred each year resulting in approximately one in five children in the
      unvaccinated group having an influenza A related clinic visit. For influenza A,
      two doses of TIV showed yearly efficacies that ranged from 42% to 69% with the
      highest efficacy during the 2002/2003 influenza season when the vaccine strains
      were well matched with the circulating viruses. The overall efficacy of two doses
      of TIV against influenza A and B associated illness was 52% and 59%,
      respectively. TIV also reduced the rate of the influenza associated
      hospitalizations attributable to both influenza A and B. CONCLUSIONS: Vaccination
      with two doses of TIV was consistently effective in preventing influenza
      associated clinic visits and hospitalizations.

PMID- 21195803
TI  - Long term recall of memory CD8 T cells in mice to first and third generation
      smallpox vaccines.
AB  - Since long-term immunity is a critical component of any effective vaccine, we
      compared over a 15-month period, the strength, durability and specificity of
      immunity of an attenuated smallpox vaccine Modified Vaccinia Ankara (MVA) to the
      New York City Board of Health (NYCBH) vaccine. The frequencies of CD8(+) T cells
      to an immunodominant CD8 T cell epitope B8R(20-27) remained remarkably stable in
      mice given either MVA or NYCBH. Both groups were also protected from a lethal
      intranasal challenge with Western Reserve strain of vaccinia virus (VACV-WR).
      Cytokine responses to virus-specific peptides were detectable with significant
      boosting upon challenge. Expression of most phenotypic markers that define
      antigen-specific memory CD8 T cells was similar while CD27 was differentially
      expressed on lung-specific T cells compared to the spleen. Our data indicate
      robust vaccinia-specific CD8(+) T cell recall responses to lethal secondary
      challenge in protected mice with no apparent effect of age on T cell pools
      established much earlier in life.

PMID- 21195804
TI  - Enhancement of antigen specific humoral immune responses after delivery of a DNA
      plasmid based vaccine through a contact-independent helium plasma.
AB  - Non-viral in vivo delivery of DNA, encoding for specific proteins, has
      traditionally relied on chemical or physical forces applied directly to tissues.
      Physical methods typically involve contact between an applicator/electrode and
      tissue and often results in transient subject discomfort. To overcome these
      limitations of contact-dependent delivery, a helium plasma source was utilized to
      deposit ionized gasses to treatment/vaccination sites without direct contact
      between the applicator and the tissues. The study reported here evaluated the
      efficacy of this strategy as an effective method to administer DNA vaccines.
      Balb/C mice were vaccinated with a DNA plasmid expressing an HIVgp120 envelope
      glycoprotein either with or without co-administration of helium plasma or
      electroporation. The results indicated, for the first time, the potential
      efficacy of helium plasma delivery for the induction and enhancement of antigen
      specific immune responses following DNA vaccination.

PMID- 21195805
TI  - Protection of pigs against Chlamydia trachomatis challenge by administration of a
      MOMP-based DNA vaccine in the vaginal mucosa.
AB  - Plasmid DNA (pWRG7079::MOMP) expressing the major outer membrane protein of a
      human Chlamydia trachomatis serovar E strain was tested for the ability to induce
      an immune response and protect against experimental genital infection with the
      same serovar. The vaccine was tested in pigs, as they are genetically and
      physiologically related to humans and suitable for studying C. trachomatis
      infection of the genital system. To increase the immune response, GM-CSF, LTA and
      B and CpG motives were used as adjuvants. GM-CSF was administered seven days
      before immunization, while the other adjuvants were administered together with
      the vaccine. Ten pigs were randomly divided into two groups. One group received
      an intravaginal primo-vaccination and a booster of 500 MUg pWRG7079::MOMP, while
      the other group received the placebo vaccine pWRG7079. All animals were
      challenged with 10(8) TCID(50) of C. trachomatis serovar E. Pigs immunized with
      the DNA vaccine showed significantly less macroscopic lesions, vaginal excretion
      and chlamydial replication in the genital tract, as compared to placebo
      vaccinated controls. However, infection could not be completely cleared.

PMID- 21195806
TI  - Do chromosomally abnormal pregnancies really preclude autoimmune etiologies of
      spontaneous miscarriages?
AB  - OBJECTIVE: At least 60% of spontaneous pregnancy loss is considered genetic in
      nature. Miscarriages can, however, also be autoimmune-induced or have other
      etiologies. Current clinical dogma in rheumatology as well as
      obstetrics/gynecology holds that evidence of aneuploidy in products of conception
      establishes the cause of miscarriage and rules out other potential causes,
      including autoimmunity. METHODS: This communication reviews published evidence in
      potential support or repudiation of this dogma via a literature search of
      appropriate keywords via PubMed and Medline. RESULTS: The literature suggests
      that maternal autoimmunity, in itself, may increase the risk towards non
      dysjunctional events and, therefore, aneuploidy prevalence in abortuses and
      offspring. CONCLUSIONS: Detection of aneuploidy in products of conception should
      no longer be considered conclusive evidence of a chromosomally induced
      miscarriage and that autoimmune evaluations should be withheld. Indeed, an
      opposite conclusion may have to be reached, suggesting, at least in repeat
      aborters, careful evaluation of autoimmune status.

PMID- 21195807
TI  - gammadelta T cells and multiple sclerosis: Friends, foes, or both?
AB  - Multiple sclerosis (MS) is a debilitating CNS disease characterized by
      demyelination and neuro-axonal loss. Though the exact etiology is still unknown,
      accumulated evidence points to the immune system being involved in the MS disease
      process. Both ill-fated adaptive and innate immune responses can potentially
      contribute to the etiopathogenesis. We have been interested in deciphering how
      innate immunity might be involved; in particular, the role of gammadelta T cells.
      In this review, we discuss the current understanding about gammadelta T cells and
      describe the evidence implicating them in myelin injury, neurotoxicity, and
      immunoregulation in the development of MS.

PMID- 21195808
TI  - Inflammation as "common soil" of the multifactorial diseases.
AB  - Inflammation is classically recognized as an essential step for the control of
      microbial invasion or tissue injury as well as for the maintenance of tissue
      homeostasis under a variety of noxious conditions. One of the most intriguing
      aspect of studying inflammation is the plurality of the inflammatory mediators
      that are continuously discovered (microRNAs, adipokines, inflammasomes and the
      danger signals, etc.) and their effects on target tissues. Several studies have
      demonstrated that inflammatory response represents the "common soil" of the
      multifactorial diseases, encompassing both chronic inflammatory rheumatic
      disorders and a wide variety of conditions including type 2 diabetes,
      cardiovascular and neurodegenerative diseases, obesity, cancer, asthma, and
      ageing. While the inflammatory response observed in the rheumatic disorders seems
      to be triggered by infection and injury, i.e. the main inducers of inflammation,
      in the other conditions mentioned it appears to be supported by tissue
      malfunction or homeostatic imbalance. In the present review, we discuss the data
      emerged from research on inflammatory mediators sustaining multifactorial
      diseases.

PMID- 21195809
TI  - Respiratory mechanics in 1-day old chicken hatchlings and effects of prenatal
      hypoxia.
AB  - This study examined the static and dynamic properties of the respiratory system
      in avian hatchlings, and the effects of incubation in hypoxia (15% O(2)) on these
      variables. In 1-day old chicken (Gallus gallus) hatchlings killed by an
      anesthetic overdose the static compliance of the respiratory system (C(rs)) was
      measured from the pressure-volume curve, constructed by step changes in lung
      volume. The dynamic compliance, C(rs)(dyn), resistance, R(rs), and time constant,
      tau(rs), were measured during mechanical ventilation at rates up to 90 cpm. The
      results indicated that (1) static C(rs) in hatchlings is several folds higher
      than in neonatal mammals of similar size, (2) during mechanical ventilation the
      respiratory system becomes hyperinflated and much stiffer; at 65 cpm (which is
      the respiratory frequency of hatchlings spontaneously breathing at rest)
      C(rs)(dyn) was about one tenth of the static value, (3) after prenatal hypoxia
      static C(rs), C(rs)(dyn), R(rs) and tau(rs) were similar to controls; only the
      magnitude of the hyperinflation was slightly decreased. It is concluded that in
      avian hatchlings (a) despite the large respiratory volume of the air sacs,
      expiration can occur passively because the hyperinflation greatly decreases
      C(rs)(dyn) and shortens tau(rs), and (b) prenatal hypoxia of the level tested has
      no major effects on the mechanical properties of the respiratory system.

PMID- 21195810
TI  - Self-assembled composite matrix in a hierarchical 3-D scaffold for bone tissue
      engineering.
AB  - It is of high clinical relevance in bone tissue engineering that scaffolds
      promote a high seeding efficiency of cells capable of osteogenic differentiation,
      such as human bone marrow-derived mesenchymal stem cells (hMSCs). We evaluated
      the effects of a novel polycaprolactone (PCL) scaffold on hMSC seeding
      efficiency, proliferation, distribution and differentiation. Porous PCL meshes
      prepared by fused deposition modeling (FDM) were embedded in matrix of hyaluronic
      acid, methylated collagen and terpolymer via polyelectrolyte complex
      coacervation. Scaffolds were cultured statically and dynamically in osteogenic
      stimulation medium for up to 28 days. Compared to naked PCL scaffolds, embedded
      scaffolds provided a higher cell seeding efficiency (t-test, P<0.05), a more
      homogeneous cell distribution and more osteogenically differentiated cells,
      verified by a more pronounced gene expression of the bone markers alkaline
      phosphatase, osteocalcin, bone sialoprotein I and bone sialoprotein II. Dynamic
      culture resulted in higher amounts of DNA (day 14 and day 21) and calcium (day 21
      and day 28), compared to static culture. Dynamic culture and the embedding
      synergistically enhanced the calcium deposition of hMSC on day 21 and day 28.
      This in vitro study provides evidence that hybrid scaffolds made from natural and
      synthetic polymers improve cellular seeding efficiency, proliferation,
      distribution and osteogenic differentiation.

PMID- 21195811
TI  - A new 17p13.3 microduplication including the PAFAH1B1 and YWHAE genes resulting
      from an unbalanced X;17 translocation.
AB  - Submicroscopic duplications of the genomic interval deleted in Miller-Dieker
      syndrome (MDS) were recently identified by array-based comparative genomic
      hybridization (a-CGH) studies, describing new genomic disorders in the MDS locus.
      These rearrangements of varying size, from 59-88 kb to 4 Mb, were non-recurrent,
      and appear to result from diverse molecular mechanisms. Only five patients had
      overlapping 17p13.3 duplications including the entire MDS critical region. We
      describe here a 13-year-old girl with a novel microduplication of the MDS
      critical region, involving the PAFAH1B1 and YWHAE genes. She presented with
      moderate psychomotor retardation, speech delay, behavioral problems, and
      bilateral cleft lip and palate, a previously unreported manifestation. Initially
      diagnosed as having an apparently simple terminal Xq26 deletion on standard
      cytogenetic analysis, she was found to have an associated terminal 4.2 Mb 17p13.3
      submicroscopic duplication, identified by subtelomere FISH analysis, further
      characterized by high-resolution array CGH, resulting from an unbalanced X;17
      translocation. Phenotypic comparison with the 5 other patients previously
      described, revealed common phenotypic features, such as hypotonia, mild to
      moderate developmental delay/mental retardation, speech abnormalities, behavioral
      problems, recurrent infections, relatively increase of body weight, discrete
      facial dysmorphism including downslanting palpebral fissures, broad midface,
      pointed chin, contributing to further delineate this new 17p13.3 microduplication
      syndrome.

PMID- 21195812
TI  - Atypical fractures and bisphosphonate therapy: a cohort study of patients with
      femoral fracture with radiographic adjudication of fracture site and features.
AB  - Atypical subtrochanteric/femoral shaft (ST/FS) fractures are increasingly
      reported in patients on long-term treatment with bisphosphonates (BPs). We
      estimated the frequency of atypical fractures and their association to BP use in
      patients aged >= 50 years consecutively admitted to a single center with a new
      femoral fracture. All individual radiographs were examined and fracture site
      confirmed. A case-control study of patients with low-energy ST/FS fractures, age-
      and sex-matched with patients with hip fractures (1:2 ratio), was performed.
      Patients with atypical ST/FS fractures were further compared with those with
      ordinary ST/FS fractures. Cortical thickness (CT) was measured in radiographs of
      cases and controls. Ninety-six of 906 patients (10.6%) had a ST/FS fracture. Of
      these, 63 with low-energy fractures were individually matched with 126 controls
      with hip fracture. BPs were used by 9.5% of cases and by 8.7% of controls (OR,
      1.10; 95% CI, 0.39-3.06) with comparable duration of therapy between groups (54
      +/- 35 vs. 54 +/- 52 months, P=0.53). CT was comparable between cases and
      controls, BP users and non-users, and was not related to treatment duration.
      Atypical fractures were observed in 10/63 ST/FS cases (15.9%). Compared to
      patients with ordinary ST/FS fractures, those with atypical fractures were using
      more frequently BPs (OR, 17.0; 95% CI, 2.6-113.3) and glucocorticoids (OR, 5.3;
      95% CI, 0.9-28.6). Among patients with atypical fractures, CT was comparable
      between BP users and non-users. In conclusion, atypical femoral fractures have a
      low prevalence (1.1% of all femoral fractures), compared to ordinary ST/FS
      fractures are more frequent in bisphosphonate users, but equally occur in
      patients never treated with bisphosphonates.

PMID- 21195813
TI  - Clinical efficacy and immunological impact of tacrolimus in Chinese patients with
      generalized myasthenia gravis.
AB  - In this multicenter, open-label pilot study, the efficacy, safety, and
      immunological impact of tacrolimus in Chinese patients with generalized
      myasthenia gravis are assessed. Forty-seven generalized myasthenia gravis (MG)
      patients were enrolled into this study and given 3mg/day tacrolimus for 24 weeks.
      The primary efficacy measurements used to monitor response to tacrolimus in MG
      patients were the Osserman grade, the quantitative MG score (QMGS) recommended by
      the MGFA, the MG-specific manual muscle testing (MMT) score, and the MG-related
      activities of daily living (MG-ADL) scale. Also, reduction in steroid doses was
      used to monitor the effect of tacrolimus. Clinical evaluations were conducted at
      weeks 4, 8, 12, 16, 20, and 24, while immunological parameters were measured at
      weeks 4, 12, and 24. Measurements of the Osserman grade, QMGS, MMT, and MG-ADL
      all suggested improvement in patient health by the fourth week of treatment.
      Steroid dosage was reduced during the course of the study in 74.2% of the forty
      three patients who completed the study. There were thirty-one reported adverse
      events in the study. Only one was considered serious. We found that tacrolimus
      reduced levels of the IFN-gamma, IL-2, IL-10, and IL-13 cytokines and induced the
      proliferation of tolerogenic plasmacytoid dendritic cells after treatment.
      Tacrolimus did not change the population of T cell subtypes but did steadily
      reduce the population of BAFF-R(+) CD19(+) B cells over the course of the study.
      Our results show that tacrolimus improves the clinical condition of MG patients
      and is well tolerated. The decrease in IL-13 and reduction of BAFF-R(+) CD19(+) B
      cells may be related to the therapeutic effect of tacrolimus.

PMID- 21195814
TI  - H1521, a novel derivative of 4-hydroxyquinoline-3-carboxamide, suppresses the
      development of lupus in mice by inducing Th1 cytokine profile in T cells.
AB  - Transferring parental splenocytes into unirradiated F1 mice induces a chronic
      graft-versus-host disease (GVHD), characterized by the production of Th2
      cytokines and immunocomplex-mediated glomerulonephritis resembling systemic lupus
      erythematosus (SLE). The effects of H1521, a new derivative of 4-hydroxyquinoline
      3-carboxamide, were investigated in chronic GVHD lupus model. H1521 was
      administered to chronic GVHD mice for 10 weeks. Nephritic symptoms were monitored
      and cytokine expression in the spleen was detected. To clarify the direct effect
      of H1521 on CD4(+) T cell, CD4(+) T cells were isolated and co-cultured with
      H1521 under neutral and Th1 or Th2 driving conditions in vitro. H1521 (32 mg/kg)
      reduced the incidence of proteinuria by 50% in chronic GVHD mice. Ameliorated
      lupus symptoms and improved renal histopathology damage were also observed.
      Administration of H1521 had little impact on Th1 cytokine IL-2 and IFN-gamma or
      Th2 cytokine IL-4 and IL-10 mRNA expression. In contrast, severely deficient IFN
      gamma production by concanavalin A-stimulated spleen cells in chronic GVHD mice
      was completely restored by H1521. In accordance with this, decreased T-bet mRNA
      expression became normalized with H1521 (32 mg/kg) treatment. In addition, in
      vitro studies demonstrated that H1521 preferentially favored Th1 differentiation
      in CD4(+) T cell and promoted IFN-gamma secretion in Th1 differential CD4(+) T
      cell. However, IL-4 secretion in naive or Th2 differential CD4(+) T cell was
      unaffected by H1521. In conclusion, H1521 can induce Th1 cytokine profile in
      CD4(+) T cells and has possible therapeutic value in Th2-predominant immune
      diseases.

PMID- 21195815
TI  - Reliability and validity of the Brazilian-Portuguese version of the Burns
      Specific Pain Anxiety Scale (BSPAS).
AB  - BACKGROUND: Pain and anxiety are a common problem in all recovery phases after a
      burn. The Burns Specific Pain Anxiety Scale (BSPAS) was proposed to assess
      anxiety in burn patients related to painful procedures. OBJECTIVES: To assess
      internal consistency, discriminative construct validity, dimensionality and
      convergent construct validity of the Brazilian-Portuguese version of the Burns
      Specific Pain Anxiety Scale. DESIGN: In this cross-sectional study, the original
      version of the BSPAS, adapted into Brazilian Portuguese, was tested for internal
      consistency (Cronbach's Alpha), discriminative validity (related to total body
      surface area burned and sex), dimensionality (through factor analysis), and
      convergent construct validity (applying the Visual Analogue Scale for pain and
      State-Anxiety-STAI) in a group of 91 adult burn patients. RESULTS: The adapted
      version of the BSPAS displayed a moderate and positive correlation with pain
      assessments: immediately before baths and dressings (r=0.32; p<0.001),
      immediately after baths and dressings (r=0.31; p<0.001) and during the relaxation
      period (r=0.31; p<0.001) and with anxiety assessments (r=0.34; p<0.001). No
      statistically significant differences were observed when comparing the mean of
      the adapted version of the BSPAS scores with sex (p=0.194) and total body surface
      area burned (p=0.162) (discriminative validity). The principal components
      analysis applied to our sample seems to confirm anxiety as one single domain of
      the Brazilian-Portuguese version of the BSPAS. Cronbach's Alpha showed high
      internal consistency of the adapted version of the scale (0.90). CONCLUSION: The
      Brazilian-Portuguese version of the BSPAS 9-items has shown statically acceptable
      levels of reliability and validity for pain-related anxiety evaluation in burn
      patients. This scale can be used to assess nursing interventions aimed at
      decreasing pain and anxiety related to the performance of painful procedures.

PMID- 21195820
TI  - Sterility of reusable transrectal ultrasound transducer assemblies for prostate
      biopsy reprocessed according to food and drug administration guidelines-
      bacteriologic outcomes in a clinical setup.
AB  - OBJECTIVES: To test the effectiveness of the sterilization process of the
      transducer while applying the Food and Drug Administration recommendations on a
      routine basis in a high-volume clinical setup. In June 2006, the Food and Drug
      Administration issued a Public Health notification about reprocessing of the
      reusable ultrasound transducer assemblies used for transrectal biopsy of the
      prostate. METHODS: Transrectal ultrasound assembly components were systematically
      swabbed and cultured. The ultrasound gel and disinfectant fluid were also
      cultured. RESULTS: A total of 42 sets of cultures from 4 predetermined locations
      were obtained (n = 168). Bacterial growth was demonstrated in 2 sets of cultures,
      both from the transducer working channel (2 of 168, 1.19%): Streptococcus
      viridans from the distal orifice of the working channel and coagulase-negative
      staphylococcus from the proximal orifice. No bacterial growth was found in the
      gel samples or in the disinfectant fluid. No patient experienced a symptomatic
      urinary tract infection or sepsis, regardless of the culture results.
      CONCLUSIONS: Processing transrectal ultrasound biopsy transducer assemblies using
      the Food and Drug Administration recommendations achieved sterility in 98.8% of
      the cultures tested and in 95.2% of the consecutive cycles of equipment
      preparations.

PMID- 21195821
TI  - Editorial comment.

PMID- 21195823
TI  - Editorial comment.

PMID- 21195824
TI  - Lower urinary tract symptoms and urinary flow rates in female patients with
      hyperthyroidism.
AB  - OBJECTIVES: To investigate lower urinary tract symptoms (LUTS) and voiding
      function in a cohort of hyperthyroid women. The autonomic nervous system (ANS)
      imbalance has been thought to cause LUTS in hyperthyroidism. METHODS: Between
      January 2008 and December 2008, 65 newly diagnosed, untreated female hyperthyroid
      patients were enrolled in this study. Another 62 age-matched healthy women were
      enrolled as a control group. Demographics, LUTS, urinary flow rates, hyperthyroid
      symptoms, and serum levels of thyroid hormones were recorded before and after the
      medical treatment for hyperthyroidism. RESULTS: Compared with the control group,
      the hyperthyroid patients had a higher mean symptom score of frequency (1.15 +/-
      1.75 vs 0.31 +/- 1.05, P = .01), incomplete emptying (0.91 +/- 1.47 vs 0.29 +/-
      1.12, P = .02), straining (1.05 +/- 0.85 vs 0.27 +/- 0.51, P <.01), voiding
      symptoms (3.05 +/- 3.28 vs 1.06 +/- 2.63, P <.01), and total symptoms (5.88 +/-
      6.17 vs 2.76 +/- 4.65, P <.01). Fifty-three (81.5%) of them had an IPSS of <8,
      while only 12 (18.5%) had an International Prostate Symptom Score (IPSS) of >=8.
      Hyperthyroid women demonstrated a lower mean peak flow rate (25.0 +/- 5.3 vs 28.6
      +/- 6.1 mL/s, P = .02). After treatment, both LUTS and flow rates improved
      significantly. The severity of LUTS was associated with neither serum levels of
      thyroid hormone nor other hyperthyroid symptoms. CONCLUSIONS: Hyperthyroid women
      have worse LUTS and lower peak flow rates than healthy controls. However, the
      severity of LUTS is only mild (IPSS <8) in the majority, and only 18.5% have
      moderate-to-severe LUTS. Both LUTS and flow rates improve after the treatment for
      hyperthyroidism. The exact mechanisms of LUTS and/or lower urinary tract
      dysfunction in hyperthyroidism require further investigation.

PMID- 21195825
TI  - Predictors of hemorrhage after laparoscopic partial nephrectomy.
AB  - OBJECTIVES: To identify risk factors associated with hemorrhage during
      laparoscopic partial nephrectomy (LPN), and to determine the impact of hemorrhage
      on hospital course. METHODS: We retrospectively analyzed prospective data from
      335 LPNs to identify clinicopathologic factors associated with hemorrhagic
      complications (blood loss requiring >= 1 U transfusion) and extended length of
      hospitalization (>= 3 days). We excluded patients with a coagulopathy or
      perioperative vascular injuries. RESULTS: We identified 23 patients (7%)
      undergoing LPN with hemorrhagic complications (group 1 and 312 patients (93%)
      without complications (group 2). Mean age was 64.1 +/- 14.4 vs 57.6 +/- 12.7(P =
      .006), American Society of Anesthesiologists (ASA) score >= 3 seen in 61% vs 37%
      (P = .02), mean tumor size (cm) was 2.90 +/- 2.02 vs 2.59 +/- 1.15 (P = .93),
      mean total operative time (min) was 250.1 +/- 116.1 vs 191.8 +/- 69.2 (P =
      0.006), and mean hospital stay (days) was 4.7 +/- 3.4 vs 3.1 +/- 3.0 (P = .0002),
      for groups 1 and 2, respectively. Hypertension, diabetes mellitus, chronic renal
      insufficiency, obesity, smoking, and coronary artery disease-congestive heart
      failure were present in group 1 vs group 2: 39.1% vs 31.4% (P = .4), 17.4% vs 8%
      (P = .12), 8.7% vs 1.9% (P = .09), 4.3% vs 3.5% (P = .57), 17.4% vs 5.4% (P =
      .04), and 8.7% vs 2.2% (P = .11), respectively. On multivariate analysis, smoking
      (P < .0437) and ASA score >= 3 (P < .0233) were associated with hemorrhagic
      complications. Hemorrhagic complications were 3.5 times more likely in smokers
      than nonsmokers (95% confidence interval, 1.0-11.7), and 2.9 times more likely
      with an ASA class >= 3. Only age (P < .0002) and operative time (P < .0001) were
      associated with longer hospitalization. CONCLUSIONS: High ASA scores and smoking
      are risk factors for hemorrhagic complications during LPN. Hemorrhagic
      complications did not significantly affect hospitalization length.

PMID- 21195826
TI  - Editorial comment.

PMID- 21195828
TI  - Editorial comment.

PMID- 21195829
TI  - Oral L-citrulline supplementation improves erection hardness in men with mild
      erectile dysfunction.
AB  - OBJECTIVES: To test the efficacy and safety of oral L-citrulline supplementation
      in improving erection hardness in patients with mild erectile dysfunction (ED). L
      arginine supplementation improves nitric oxide-mediated vasodilation and
      endothelial function; however, oral administration has been hampered by extensive
      presystemic metabolism. In contrast, L-citrulline escapes presystemic metabolism
      and is converted to L-arginine, thus setting the rationale for oral L-citrulline
      supplementation as a donor for the L-arginine/nitric oxide pathway of penile
      erection. METHODS: In the present single-blind study, men with mild ED (erection
      hardness score of 3) received a placebo for 1 month and L-citrulline, 1.5 g/d,
      for another month. The erection hardness score, number of intercourses per month,
      treatment satisfaction, and adverse events were recorded. RESULTS: A total of 24
      patients, mean age 56.5 +/- 9.8 years, were entered and concluded the study
      without adverse events. The improvement in the erection hardness score from 3
      (mild ED) to 4 (normal erectile function) occurred in 2 (8.3%) of the 24 men when
      taking placebo and 12 (50%) of the 24 men when taking L-citrulline (P < .01). The
      mean number of intercourses per month increased from 1.37 +/- 0.93 at baseline to
      1.53 +/- 1.00 at the end of the placebo phase (P = .57) and 2.3 +/- 1.37 at the
      end of the treatment phase (P < .01). All patients reporting an erection hardness
      score improvement from 3 to 4 reported being very satisfied. CONCLUSIONS:
      Although less effective than phosphodiesterase type-5 enzyme inhibitors, at least
      in the short term, L-citrulline supplementation has been proved to be safe and
      psychologically well accepted by patients. Its role as an alternative treatment
      for mild to moderate ED, particularly in patients with a psychologically fear of
      phosphodiesterase type-5 enzyme inhibitors, deserves further research.

PMID- 21195830
TI  - Phosphodiesterase-5 inhibitors for lower urinary tract symptoms secondary to
      benign prostatic hyperplasia: a systematic review and meta-analysis.
AB  - OBJECTIVES: To evaluate the efficacy and safety of phosphodiesterase-5 (PDE-5)
      inhibitors for treating lower urinary tract symptoms secondary to benign
      prostatic hyperplasia. METHODS: Randomized controlled trials were identified and
      extracted from MEDLINE, Embase, Cochrane Central, and relevant reference lists.
      The database search, quality assessment, and data extraction were independently
      performed by 2 reviewers. Heterogeneity was analyzed using the chi-square test
      and I(2) test. If lacking of heterogeneity, fixed-effects models were used for
      the meta-analysis, otherwise random-effects models were used. RESULTS: A total of
      5 studies (11 randomized controlled trials) were identified from the search
      strategy. Compared with placebo, short-term trials (<=12 weeks) indicated that
      PDE-5 inhibitors significantly improved the International Prostate Symptom Score
      (mean difference -2.60, 95% confidence interval [CI] -3.12 to -2.07; P < .00001),
      and statistical significance was observed in the International Prostate Symptom
      Score irritative and obstructive subscore, International Prostate Symptom Score
      quality of life and erectile function. However, no statistically significant
      difference was detected in maximal urinary flow rate (mean difference 0.21, 95%
      CI -0.21-0.64; P = .32) and postvoid residual urine volume (mean difference 0.09,
      95% CI -4.71-4.89; P = .80). No statistically significant difference was found
      between the 2 groups in the incidence of serious adverse events (relative risk
      0.52, 95% CI 0.25-1.07; P = .07), despite that adverse event with a greater
      incidence was detected in the PDE-5 group (relative risk 1.87, 95% CI 1.31-2.68;
      P = .0005). CONCLUSIONS: As the first-line treatment of erectile dysfunction, the
      PDE-5 inhibitor is also effective and safe for lower urinary tract symptoms
      secondary to benign prostatic hyperplasia. It could be considered as the first
      line treatment in the future for the treatment of patients with comorbid benign
      prostatic hyperplasia and erectile dysfunction.

PMID- 21195831
TI  - Editorial comment.

PMID- 21195833
TI  - Editorial comment.

PMID- 21195834
TI  - Editorial comment.

PMID- 21195835
TI  - Distribution of PSA velocity by total PSA levels: data from the Baltimore
      Longitudinal Study of Aging.
AB  - OBJECTIVES: To describe the distribution and implications of prostate-specific
      antigen velocity (PSAV) by prostate-specific antigen (PSA) in an unselected
      population. A PSAV >0.35 and >2.0 ng/mL/y have been associated with an increased
      risk of prostate cancer (CaP) death more than 10 years and 1 year before
      diagnosis, respectively. It is unknown how frequently PSAVs of this magnitude
      occur in community men. METHODS: From the Baltimore Longitudinal Study of Aging,
      we examined the PSAV distribution in 786 men with serial PSA measurements (3474
      PSAV observations) at total PSA levels <10 ng/mL. We also determined whether PSAV
      altered the probability of overall and life-threatening CaP at PSA levels <3 and
      3-10 ng/mL. RESULTS: Overall, the mean PSA and PSAV were 1.3 ng/mL and 0.05
      ng/mL/y, respectively. PSAV rose continuously with increasing PSA (P <.0001), and
      was significantly higher in cancers than controls for observations at PSA levels
      <3 ng/mL (P = .02) and 3-10 ng/mL (P = .0008). The probability of life
      threatening CaP was 3% at a PSA <3 ng/mL, but increased to 13.6% with PSAV >0.4
      ng/mL/y. At PSA levels of 3-10 ng/mL, the probability of life-threatening CaP was
      9.8% based on PSA alone vs 12% with PSAV >0.4 ng/mL/y. CONCLUSIONS: PSAV was
      significantly higher in CaP observations than controls in all PSA ranges studied
      and altered the risk of overall and life-threatening CaP at a given PSA level.
      Because the value of PSAV is PSA-dependent, the PSA level should be taken into
      account when interpreting PSAV.

PMID- 21195836
TI  - Editorial comment.

PMID- 21195838
TI  - Editorial comment.

PMID- 21195839
TI  - Editorial comment.

PMID- 21195840
TI  - Editorial comment.

PMID- 21195842
TI  - Editorial comment.

PMID- 21195844
TI  - alpha-Methylacyl-CoA racemase spliced variants and their expression in normal and
      malignant prostate tissues.
AB  - OBJECTIVES: To evaluate the possibility of using alpha-methylacyl-CoA racemase
      (AMACR) variants to improve the specificity of prostate cancer (CaP) detection.
      AMACR has been used as a diagnostic biomarker for CaP and is now a standard
      biomarker for needle biopsy specimens with ambiguous lesions. METHODS: We used in
      silico analysis and molecular cloning to discover new AMACR variants and
      quantitative reverse transcription-polymerase chain reaction (RT-PCR) to measure
      the transcript levels of AMACR and its variants in 4 prostate cell lines and in
      23 pairs of CaP and adjacent normal tissue. RESULTS: We found 4 novel variants,
      IAs, IBL, IBLd, and IBLi. Transcript levels of most AMACR variants were
      significantly upregulated in CaP compared with its adjacent normal counterparts.
      A variants, the functional variants based on bioinformatic analysis, showed
      levels of transcript expression in CaP in this order: IA?IAd=IIA?IIAs>IAs. In
      contrast, the expression of the B variants, which appear to be nonfunctional due
      to the absence of exon 3, was lower than that of the A variants. IB was the most
      abundant form of B variant; and expression of IIB was negligible. More important,
      the difference between levels of variant IA, IAd, IIA, IIAs, IB, and IBLi in CaP
      and normal tissue was significantly higher than the difference in levels of total
      AMACR. CONCLUSIONS: Our data suggest that AMACR variants have better power than
      total AMACR in discriminating between CaP and adjacent normal tissue. These
      findings may be useful for the development of future diagnostic assays.

PMID- 21195845
TI  - Re: Matsumotu et al.: Late recurrence and progression in non-muscle-invasive
      bladder cancers after 5-year tumor-free periods (Urology 2010;75:1385-1391).

PMID- 21195847
TI  - Re: Miyajima et al.: How do young residents practice laparoscopic surgical
      skills? (Urology 2010;76:352-356).

PMID- 21195849
TI  - Re: Tollefson et al.: Surgical treatment of renal cell carcinoma in the
      immunocompromised transplant patient (Urology 2010;75:1373-1377).

PMID- 21195850
TI  - Re: Endo et al.: Anteroposterior dissection HoLEP: a modification to prevent
      transient stress urinary incontinence (Urology 2010;76:1451-1455).

PMID- 21195852
TI  - Lessons learned from a cryptic penile amputation.

PMID- 21195853
TI  - Re: Ray et al.: Limitations to ultrasound in the detection and measurement of
      urinary tract calculi (Urology 2010;76:295-300).

PMID- 21195855
TI  - Re: Jiang et al.: Meta-analysis of association between TP53 Arg72Pro polymorphism
      and bladder cancer risk (Urology 2010;76:765).

PMID- 21195856
TI  - Re: Lasser et al.: An unbiased prospective report of perioperative complications
      of robot-assisted laparoscopic radical prostatectomy (Urology 2010;75:1083-1091).

PMID- 21195857
TI  - Re: Hayashi et al.: A Japanese view on circumcision: nonoperative management of
      normal and abnormal prepuce (Urology 2010;76:21-24).

PMID- 21195859
TI  - Re: Williams et al.: Radical retropubic prostatectomy and robotic-assisted
      laparoscopic prostatectomy: likelihood of positive surgical margin(s) (Urology
      2010;76:1097-1101).

PMID- 21195861
TI  - Re: Williams et al.: Radical retropubic prostatectomy and robotic-assisted
      laparoscopic prostatectomy: likelihood of positive surgical margin(s) (Urology
      2010;76:1097-1101).

PMID- 21195874
TI  - Prognostic cell biological markers in cervical cancer patients primarily treated
      with (chemo)radiation: a systematic review.
AB  - The aim of this study was to systematically review the prognostic and predictive
      significance of cell biological markers in cervical cancer patients primarily
      treated with (chemo)radiation. A PubMed, Embase, and Cochrane literature search
      was performed. Studies describing a relation between a cell biological marker and
      survival in >=50 cervical cancer patients primarily treated with (chemo)radiation
      were selected. Study quality was assessed, and studies with a quality score of 4
      or lower were excluded. Cell biological markers were clustered on biological
      function, and the prognostic and predictive significance of these markers was
      described. In total, 42 studies concerning 82 cell biological markers were
      included in this systematic review. In addition to cyclooxygenase-2 (COX-2) and
      serum squamous cell carcinoma antigen (SCC-ag) levels, markers associated with
      poor prognosis were involved in epidermal growth factor receptor (EGFR) signaling
      (EGFR and C-erbB-2) and in angiogenesis and hypoxia (carbonic anhydrase 9 and
      hypoxia-inducible factor-1alpha). Epidermal growth factor receptor and C-erbB-2
      were also associated with poor response to (chemo)radiation. In conclusion, EGFR
      signaling is associated with poor prognosis and response to therapy in cervical
      cancer patients primarily treated with (chemo)radiation, whereas markers involved
      in angiogenesis and hypoxia, COX-2, and serum SCC-ag levels are associated with a
      poor prognosis. Therefore, targeting these pathways in combination with
      chemoradiation may improve survival in advanced-stage cervical cancer patients.

PMID- 21195875
TI  - Dose escalation improves cancer-related events at 10 years for intermediate- and
      high-risk prostate cancer patients treated with hypofractionated high-dose-rate
      boost and external beam radiotherapy.
AB  - PURPOSE: To evaluate the 10-year outcomes of intermediate- and high-risk prostate
      cancer patients treated with a prospective dose escalation hypofractionated trial
      of pelvic external beam radiation therapy (P-EBRT) with a high-dose-rate (HDR)
      brachytherapy boost. METHODS AND MATERIALS: From 1992 to 2007, 472 patients were
      treated with a HDR boost at William Beaumont Hospital. They had at least one of
      the following: a prostate-specific antigen (PSA) level of >10 ng/ml, a Gleason
      score of >=7, or clinical stage >=T2b. Patients received 46-Gy P-EBRT and an HDR
      boost. The HDR dose fractionation was divided into two dose levels. The prostate
      biologically equivalent dose (BED) low-dose-level group received <268 Gy, and the
      high-dose group received >268 Gy . Phoenix biochemical failure (BF) definition
      was used. RESULTS: Median follow-up was 8.2 years (range, 0.4-17 years). The 10
      year biochemical failure rate of 43.1% vs. 18.9%, (p < 0.001), the clinical
      failure rate of 23.4% vs. 7.7%, (p < 0.001), and the distant metastasis of 12.4%
      vs. 5.7%, (p = 0.028) were all significantly better for the high-dose level
      group. On Cox multivariate analysis, higher BED levels (p = 0.017; hazard ratio
      [HR] = 0.586), pretreatment PSA assays (p < 0.001, HR = 1.022), and Gleason
      scores (p = 0.004) were significant variables for reduced biochemical failure.
      Higher dose levels (p, 0.002; HR, 0.397) and Gleason scores (p < 0.001) were
      significant for clinical failure. Grade 3 genitourinary complications were 2% and
      3%, respectively, and grade 3 gastrointestinal complication was <0.5%.
      CONCLUSIONS: This prospective trial using P-EBRT with HDR boost and
      hypofractionated dose escalation demonstrates a strong dose-response relationship
      for intermediate- and high-risk prostate cancer patients. The improvement at 10
      years for locoregional control with higher radiation doses (BED, > 268 Gy) has
      significantly decreased biochemical and clinical failures as well as distant
      metastasis.

PMID- 21195876
TI  - Adenovirus E2F1 overexpression sensitizes LNCaP and PC3 prostate tumor cells to
      radiation in vivo.
AB  - PURPOSE: We previously showed that E2F1 overexpression radiosensitizes prostate
      cancer cells in vitro. Here, we demonstrate the radiosensitization efficacy of
      adenovirus (Ad)-E2F1 infection in growing (orthotopic) LNCaP and (subcutaneous)
      PC3 nude mice xenograft tumors. METHODS AND MATERIALS: Ad-E2F1 was injected
      intratumorally in LNCaP (3 * 10(8) plaque-forming units [PFU]) and PC3 (5 * 10(8)
      PFU) tumors treated with or without radiation. LNCaP tumor volumes (TV) were
      measured by magnetic resonance imaging, caliper were used to measure PC3 tumors,
      and serum prostate-specific antigen (PSA) levels were determined by enzyme-linked
      immunosorbent assay. Apoptosis was measured by terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick end labeling, and key proteins involved in
      cell death signaling were analyzed by Western blotting. RESULTS: Intracellular
      overexpression of Ad-E2F1 had a significant effect on the regression of TV and
      reduction of PSA levels relative to that of adenoviral luciferase (Ad-Luc)
      infected control. The in vivo regressing effect of Ad-E2F1 on LNCaP tumor growth
      was significant (PSA, 34 ng/ml; TV, 142 mm(3)) compared to that of Ad-Luc control
      (PSA, 59 ng/ml; TV, 218 mm(3); p <0.05). This effect was significantly enhanced
      by radiation therapy (compare: Ad-E2F1+RT/PSA, 16 ng/ml, and TV, 55 mm(3) to Ad
      Luc+RT/PSA, 42 ng/ml, and TV, 174 mm(3), respectively; p <0.05). For PC3 tumors,
      the greatest effect was observed with Ad-E2F1 infection alone; there was little
      or no effect when radiotherapy (RT) was combined. However, addition of RT
      enhanced the level of in situ apoptosis in PC3 tumors. Molecularly, addition of
      Ad-E2F1 in a combination treatment abrogated radiation-induced BCL-2 protein
      expression and was associated with an increase in activated BAX, and together
      they caused a potent radiosensitizing effect, irrespective of p53 and androgen
      receptor functional status. CONCLUSIONS: We show here for the first time that
      ectopic overexpression of E2F1 in vivo, using an adenoviral vector, significantly
      inhibits orthotopic p53 wild-type LNCaP tumors and subcutaneous p53-null PC3
      tumors in nude mice. Furthermore, we demonstrate that E2F1 strongly sensitizes
      LNCaP tumors to RT. These findings suggest that E2F1 overexpression can sensitize
      prostate tumor cells in vivo, independent of p53 or androgen receptor status.

PMID- 21195877
TI  - In vivo radiobiological characterization of proton beam at the National Cancer
      Center in Korea: effect of the Chk2 mutation.
AB  - PURPOSE: The relative biological effectiveness (RBE) in the presence or absence
      of CHK2 was estimated at the Korean National Cancer Center Proton Therapy Center
      (NCCPTC). METHODS AND MATERIALS: The proton beam was fixed at 210 MeV with 6-cm
      spread-out Bragg peaks (SOBPs) because this is expected to be the most frequently
      used clinical setting. X-rays were obtained using a 6-MV conventional linear
      accelerator. The RBE was estimated from the survival of jejunal crypt in C3H/He
      and Chk2(-/-) mice. RESULTS: The estimated RBEs of the NCCPTC at the middle of
      the SOBP were 1.10 and 1.05 in the presence and absence of CHK2, respectively.
      The doses that reduced the number of regenerated crypt per jejunal circumference
      to 20 (D(20)) in C3H/He mice were 14.8 Gy (95% confidence interval [CI], 13.7
      15.9) for X-rays and 13.5 Gy (95% CI, 14.5-15.5) for protons. By contrast, the
      doses of D(20) in Chk2(-/-) mice were 15.7 Gy (95% CI, 15.0-16.4) and 14.9 Gy
      (95% CI, 14.0-15.8) for X-rays and protons, respectively. CONCLUSIONS: The RBE of
      the NCCPTC is clearly within the range of RBEs determined at other facilities and
      is consistent with the generic RBE value of 1.10 for 150- to 250-MeV beams. The
      mutation of Chk2 gave rise to radioresistance but exhibited similar RBE.

PMID- 21195878
TI  - Treatment of HER2-expressing breast cancer and ovarian cancer cells with alpha
      particle-emitting 227Th-trastuzumab.
AB  - PURPOSE: To evaluate the cytotoxic effects of low-dose-rate alpha particle
      emitting radioimmunoconjugate (227)Th-p-isothiocyanato-benzyl-DOTA-trastuzumab
      ((227)Th-trastuzumab [where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10
      tetraacetic acid]) internalized by breast and ovarian cancer cell lines in order
      to assess the potential of (227)Th-trastuzumab as a therapeutic agent against
      metastatic cancers that overexpress the HER2 oncogene. METHODS AND MATERIALS:
      Clonogenic survival and cell growth rates of breast cancer cells treated with
      (227)Th-trastuzumab were compared with rates of cells treated with nonbinding
      (227)Th-rituximab, cold trastuzumab, and X-radiation. Cell growth experiments
      were also performed with ovarian cancer cells. Cell-associated radioactivity was
      measured at several time points, and the mean radiation dose to cells was
      calculated. RESULTS: SKBR-3 cells got 50% of the mean absorbed radiation dose
      from internalized activity and 50% from cell surface-bound activity, while BT-474
      and SKOV-3 cells got 75% radiation dose from internalized activity and 25% from
      cell surface-bound activity. Incubation of breast cancer cells with 2.5 kBq/ml
      (227)Th-trastuzumab for 1 h at 4 degrees C, followed by washing, resulted in mean
      absorbed radiation doses of 2 to 2.5 Gy. A dose-dependent inhibition of cell
      growth and an increase in apoptosis were induced in all cell lines. CONCLUSIONS:
      Clinically relevant activity concentrations of (227)Th-trastuzumab induced a
      specific cytotoxic effect in three HER2-expressing cell lines. The cytotoxic
      effect of (227)Th-trastuzumab was higher than that of single-dose X-radiation
      (relative biological effectiveness = 1.2). These results warrant further studies
      of treatment of breast cancer and ovarian cancer with (227)Th-trastuzumab.

PMID- 21195880
TI  - Radiosensitivity of human papillomavirus-related tumors: in regard to Gupta et
      al. (Int J Radiat Oncol Biol Phys 2009;74:928-933).

PMID- 21195881
TI  - Postoperative radiation for prevention of heterotopic ossification of the elbow:
      primary or secondary prophylaxis? In regard to Robinson CG et al. (Int J Radiat
      Oncol Biol Phys 2010;77:1493-1499).

PMID- 21195883
TI  - Recent advances in clinical application of gut hormones.

PMID- 21195884
TI  - Urinary nerve growth factor levels in overactive bladder syndrome and lower
      urinary tract disorders.
AB  - Overactive bladder (OAB) is a syndrome based on self-reported symptoms of urgency
      and frequency with or without urge incontinence. Although urgency is the core
      symptom of OAB, patients might have difficulty to distinguish urgency from the
      urge to void. Urodynamic study is a useful diagnostic tool to discover detrusor
      overactivity (DO) in patients with OAB; however, not all OAB patients have DO.
      Therefore, a more objective and non-invasive way to diagnose and assess OAB
      including DO is needed. Recent research has focused on urinary biomarkers in
      assessment of OAB. Urinary nerve growth factor (NGF) level increases in patients
      with OAB-wet, bladder outlet obstruction, mixed urinary incontinence and
      urodynamic DO. Urinary NGF levels are correlated with severity of OAB symptoms.
      In patients with OAB and DO who have been well treated with antimuscarinics or
      botulinum toxin injection, urinary NGF levels have been shown to decrease
      significantly in association with reduction of urgency severity. However, not all
      patients with OAB have an elevated urinary NGF level. It might also be increased
      in patients with interstitial cystitis/painful bladder syndrome, cerebrovascular
      accident and lower urinary tract diseases such as urinary tract stone, bacterial
      infection and urothelial tumor. It is possible to use urinary NGF levels as a bio
      marker for diagnosis of OAB as well as for the assessment of therapeutic outcome
      in patients with OAB or DO. Here, we review the latest medical advances in this
      field.

PMID- 21195885
TI  - Role of pollen allergy in Taiwanese patients with allergic rhinitis.
AB  - BACKGROUND/PURPOSE: Pollen allergy is believed to be less common in East Asia,
      Latin America, and tropical areas. The purpose of this study was to understand
      the role of pollen allergy in Taiwan. METHODS: Patients with clinically diagnosed
      allergic rhinitis were enrolled. All subjects received a 30-item skin test panel
      that included perennial allergens (house dust mix, Dermatophagoides
      pteronyssinus, Dermatophagoides farinae, dog epithelium, cat hairs, cockroach
      mix, and Candida albicans) and pollen allergens (acacia, pine mix, eucalyptus,
      beefwood, juniper mix, willow, mulberry mix, pepper tree, cedar, Johnson grass,
      Bermuda grass, ragweed mix, Timothy grass, spiny pigweed, cocklebur, sage mix,
      sheep sorrel, dog fennel, pigweed mix, English plantain, castor bean, alfalfa,
      and dandelion). RESULTS: A total of 419 patients were recruited. A total of 313
      (74.7%) had a positive skin test. A total of 288 patients (68.7%) were sensitive
      to perennial allergens, and 11 8 patients (28.2%) were sensitive to pollen
      allergens. However, 93 pollen-sensitive patients were also sensitive to perennial
      allergens, and only 25 were sensitive to pollen allergens alone. The most common
      allergens were D. pteronyssinus, D. farinae, house dust mix, and cockroach, but
      the most common pollen allergens were spiny pigweed, Johnson grass, and sheep
      sorrel. All nasal symptoms tended to be more severe in patients who were
      sensitive to perennial allergens than in those who were sensitive to pollen
      allergens alone. CONCLUSION: Most patients with allergic rhinitis in Taiwan are
      sensitive to perennial allergens, and pollens are a less common allergen.

PMID- 21195886
TI  - Cluster of parvovirus infection among hospital staff working in coronary care
      units.
AB  - BACKGROUND: Parvovirus B19 is associated with erythema infectiosum in children or
      arthralgia and arthritis in adults. The virus is relatively conserved and
      nucleotide identity is expected in viruses that are epidemiologically related.
      Here, we describe the first cluster of parvovirus infection among hospital staff
      documented in Taiwan. METHODS: Active surveillance was conducted in coronary care
      units (CCUs) at a 2200-bed teaching hospital for 1 month in 2007. A case defined
      clinically as occurring in a patient or staff in CCUs with new onset of fever or
      rash. Serum was tested for parvovirus B19 IgM and IgG by immunoblotting and DNA
      by nested polymerase chain reaction. When viremia was detected, nucleotide
      sequences were analyzed and compared with those of two clinical isolates. The
      attack rate was defined as the cumulative incidence of acute infection in CCU
      staff and patients during the study period. RESULTS: Among 57 staff and 15
      patients, five nurses met the clinical case definition. Three had acute infection
      as demonstrated by viral DNA and IgM. The attack rate was 5.3% for the staff and
      zero for patients. Seroprevalence rate was lower in staff than in patients
      (26.3%vs. 53.3%). The isolates collected from three cases were highly similar to
      a community isolate, and they varied with each other by 2-6 nucleotides. The
      isolate collected from a nurse was identical to that from her friend 3 weeks
      apart and was concordant with mutual transmission. A sequence with 45 nucleotide
      variations was identified from a staff member with chronic infection who was
      negative for IgM and had only weak IgG anti-VP1 reaction with immunoblotting. We
      did not find any patient as the source of infection. CONCLUSION: We identified a
      cluster of parvovirus infection that was caused by three circulating strains
      which did not support the hypothesis of transmission of a single strain in CCUs.

PMID- 21195887
TI  - Non-attendance in endocrinology and metabolism patients.
AB  - BACKGROUND/PURPOSE: Non-attendance in outpatient clinics might disrupt medical
      care, interfere with outpatient clinic processing, and waste health service
      resources. This study was performed to identify predictive factors for non
      attendance in endocrinology and metabolism (Endo/Meta) patients. METHODS: Non
      attendance was examined for a period of 6 months in Endo/Meta outpatient clinics
      in a medical center in Taiwan. Effects of physician, clinic, and patient
      characteristics, and appointment patterns in non-attendance were assessed by
      xi(2) test and multivariate logistic regression. RESULTS: During the study
      period, a total of 13,584 patients booked appointments for 609 Endo/Meta clinics
      managed by 11 specialists. The mean number of appointments per patient was 2.3 +/
      1.1. The total number of registered visits was 31,143. The total number of non
      attendances was 2272. The overall proportion of non-attendance in Endo/Meta
      patients was 7.3%. The proportion of non-attendance varied with different
      physician teaching status and on different weekdays. In multivariate logistic
      regression, physician age (p = 0.0009), physician teaching status (p = 0.0013),
      number of physician shifts per week (p< 0.0001), patient age (p< 0.0001), first
      time appointment (p< 0.0001) and registration order in the clinic (p < 0.0001)
      had significant effects on non-attendance, whereas physician and patient sex,
      weekdays and daytimes of clinics had no significant effect on non-attendance.
      CONCLUSION: Determinants of non-attendance in Endo/Meta patients include older
      physician age, lower physician teaching status, number of physician shifts per
      week, younger patient age, first-time appointment, and later registration order
      in the clinic. Research on non-attendance should be applied to improve quality of
      medical care. Optimal ways to ensure attendance deserve further investigation.

PMID- 21195889
TI  - Echocardiography and 64-multislice computed tomography angiography in diagnosing
      coronary artery fistula.
AB  - BACKGROUND/PURPOSES: There are various types of coronary artery fistula (CAF)
      with complex shapes; therefore, it is important to obtain a correct diagnosis and
      to understand its relations to the adjacent structures before surgery. This study
      evaluated echocardiography and 64-multislice computed tomography (64-MSCT)
      angiography in diagnosing CAF. METHODS: Sixteen patients with CAF, confirmed by
      surgical operation or digital subtraction angiography, were examined by
      echocardiography. Five of them were further examined by 64-MSCT angiography for
      detailed anatomical information before surgery. The imaging data for
      echocardiography and 64-MSCT angiography were analyzed retrospectively. RESULTS:
      Among the 16 patients, 12 were correctly diagnosed by echocardiography, of whom
      five were confirmed by 64-MSCT angiography. Four cases missed diagnosis by
      echocardiography, and one of these was correctly diagnosed by 64-MSCT. Seventeen
      fistulae were found, of which, two appeared in one patient. Ten fistulae
      originated from the left coronary artery and seven from the right. The draining
      site was the right heart in eight, pulmonary artery in five, left heart in three
      and aorta in one. CONCLUSION: Echocardiography can act as the routine examination
      of CAF, and 64-MSCT angiography can provide more detailed anatomical and
      pathological information for surgery than echocardiography.

PMID- 21195888
TI  - An alternative solution to achieve primary stability in cementless revision hip
      arthroplasty for femur ectasia.
AB  - BACKGROUND/PURPOSE: Revision total hip arthroplasty is technically demanding,
      especially when treating a large defective femur. The aim of this study was to
      evaluate the clinical results of cementless total hip arthroplasty revision in
      patients with advanced femoral bony defects. METHODS: By using the canaloplasty
      technique, which osteotomized the proximal femur to reduce the width of canal, 12
      patients were enrolled and underwent revision operation. Patients were evaluated
      by radiographic examination and Harris hip score before and after the index
      procedures. RESULTS: The average length of follow-up was 38.7 months. All the
      osteotomies united at a mean of 5.3 months. Structural allografts were used on
      six patients to augment the thinned cortices. A total of 11 femoral components
      (91%) achieved and maintained stability at the last follow-up. One patient was
      complicated with early stem subsidence and another with deep infection. Both
      patients were treated successfully without late sequelae. The mean Harris hip
      score improved from 37.2 to 75.0 after the operation (p < 0.05). CONCLUSION: The
      canaloplasty technique could be an alternative solution to help revision surgery
      in some younger patients with advanced femoral defects.

PMID- 21195890
TI  - Castleman's disease in the head and neck region: Meta-analysis of reported cases
      in Taiwan and literature review.
AB  - BACKGROUND/PURPOSE: Castleman's disease (CD) is a rare and complex disease that
      involves the head and neck region. In our hospital, only three cases of CD in the
      head and neck region have been encountered in the past 20 years. METHODS: To
      establish a database of Castleman's disease in Taiwan and to compare it to
      published western studies, we collected case reports of CD in the head and neck
      region in Taiwan from 1992 to 2007. We used "Castleman's disease" and "Taiwan" as
      keywords to search medical journal databases. A total of 15 cases were
      incorporated in our study, including three from our own hospital. These data were
      integrated for studying the disease characteristics in Taiwan. RESULTS:
      Submandibular area (level I) was the most commonly involved site (5 cases,
      33.3%). The ratio of unicentric to multicentric CD and the proportion of
      histological classifications were similar to those in the western studies
      included in our review. All of the unicentric CD treated by complete resection
      showed no evidence of recurrence. Multicentric CD was present in two patients,
      although one died following a heart attack. The other multicentric CD patient was
      treated by medication and survived for several years. CONCLUSION: The features of
      head and neck CD in Taiwan are similar to those reported in western studies.
      Although CD is not a common disease, it should be considered as a differential
      diagnosis in patients with a neck mass, especially when the patient is suffering
      from long-term inflammation. Multicentric CD is also likely to be initially
      misdiagnosed as unicentric CD. It is important to remember that all patients
      diagnosed with CD should receive a systemic survey to exclude the possibility of
      ignored lesions.

PMID- 21195891
TI  - Response to "New Delhi metallo-beta-lactamase (NDM-1): an emerging threat among
      Enterobacteriaceae".

PMID- 21195892
TI  - Hepatitis associated with prothionamide for treatment of multidrug-resistant
      tuberculosis.
AB  - Timely and intensive monitoring for, and management of, adverse effects caused by
      anti-tuberculosis drugs are essential components of control programs for
      multidrug-resistant tuberculosis (MDR-TB). This retrospective case series was
      conducted in northern Taiwan from January 2007 to December 2008 at Taipei Medical
      University-Wan Fang Hospital, a 750-bed tertiary-care center and MDR-TB referral
      center. Hepatitis associated with prothionamide was defined as the recurrence of
      hepatitis after a second prothionamide treatment re-challenge. In total, 47
      patients with MDR-TB enrolled in the Directly Observed Therapy, Short Course-Plus
      Program were identified during the study period, and 44 (93.6%) were treated with
      prothionamide. Seven of these 44 patients (15.9%) developed hepatitis after being
      treated with prothionamide concurrent with other anti-tuberculosis agents.
      Hepatitis associated with prothionamide occurred in three of these seven patients
      (6.8%). In these three patients, hepatitis developed following treatment with
      prothionamide for 28 days, 39 days or 45 days. Hepatitis developed rapidly after
      re-challenge with prothionamide at 4 days, 4 days and 3 days, respectively. Liver
      function returned to the normal range after cessation of prothionamide treatment
      for 19 days, 27 days or 28 days. Close monitoring of liver function was necessary
      in MDR-TB patients who received prothionamide treatment.

PMID- 21195893
TI  - Pleural plaque related to asbestos mining in Taiwan.
AB  - A 78-year-old woman complained of twisting-like pain in her left lower chest.
      During physical examination, friction rubbing was noted in both lungs. Chest
      radiography showed extensive bilateral pleural calcification. High-resolution
      computed tomography confirmed the presence of bilateral calcified pleural
      plaques. The patient had worked at a Japanese asbestos factory in Taiwan for 1
      year when she was 16 years old. Her job involved picking out asbestos fibers from
      crushed asbestos minerals, but no protective equipment was used at that time.
      This is believed to be the first reported case of asbestos-related disease in
      Taiwan that resulted from asbestos mining. We also summarize the history of
      domestic asbestos mining, importation of asbestos, and trends in asbestos use in
      Taiwan.

PMID- 21195898
TI  - Prostatic arterial embolization to treat benign prostatic hyperplasia.
AB  - PURPOSE: To evaluate whether prostatic arterial embolization (PAE) might be a
      feasible procedure to treat lower urinary tract symptoms associated with benign
      prostatic hyperplasia (BPH). MATERIALS AND METHODS: Fifteen patients (age range,
      62-82 years; mean age, 74.1 y) with symptomatic BPH after failure of medical
      treatment were selected for PAE with nonspherical 200-MUm polyvinyl alcohol
      particles. The procedure was performed by a single femoral approach. Technical
      success was considered when selective prostatic arterial catheterization and
      embolization was achieved on at least one pelvic side. RESULTS: PAE was
      technically successful in 14 of the 15 patients (93.3%). There was a mean follow
      up of 7.9 months (range, 3-12 months). International Prostate Symptom Score
      decreased a mean of 6.5 points (P = .005), quality of life improved 1.14 points
      (P = .065), International Index of Erectile Function increased 1.7 points (P =
      .063), and peak urinary flow increased 3.85 mL/sec (P = .015). There was a mean
      prostate-specific antigen reduction of 2.27 ng/mL (P = .072) and a mean prostate
      volume decrease of 26.5 mL (P = .0001) by ultrasound and 28.9 mL (P = .008) by
      magnetic resonance imaging. There was one major complication (a 1.5-cm(2)
      ischemic area of the bladder wall) and four clinical failures (28.6%).
      CONCLUSIONS: In this small group of patients, PAE was a feasible procedure, with
      preliminary results and short-term follow-up suggesting good symptom control
      without sexual dysfunction in suitable candidates, associated with a reduction in
      prostate volume.

PMID- 21195899
TI  - Percutaneous treatment of traumatic upper-extremity arterial injuries: a single
      center experience.
AB  - PURPOSE: To assess the feasibility and effectiveness of emergency percutaneous
      treatment of traumatic injuries of upper-extremity arteries. MATERIALS AND
      METHODS: Between January 2000 and December 2007, 11 patients (mean age, 49.9
      years) with traumatic injuries of upper-extremity arteries were observed: three
      had pseudoaneurysms, four had dissections, three had transections, and one had
      mural hematoma. Lesions involved the axillary (n = 6), subclavian (n = 3), or
      brachial artery (n = 2). Pseudoaneurysms and transections were treated with stent
      grafts, (n = 6) and dissections and mural hematomas were treated with bare stents
      (n = 2) or angioplasty (n = 3). Follow-up (mean, 45.1 months; range, 12-84
      months) was performed with color Doppler ultrasonography at 1, 3, 6, and 12
      months and then, yearly. RESULTS: Immediate technical success was obtained in all
      cases. No major complications occurred; there was one asymptomatic occlusion of
      the interosseous artery and one case of incomplete thrombosis of the radial
      artery (with recanalization after 1 month with systemic medical therapy). During
      a mean follow-up of 45.1 months, one stent-graft occlusion occurred, which was
      treated with intraarterial pharmacologic thrombolysis (urokinase 60,000 IU/h for
      12 hours). Overall primary clinical success rate was 95.2% and secondary clinical
      success rate was 100%. CONCLUSIONS: Percutaneous treatment is a feasible and safe
      tool for injuries of upper-extremity arteries because it can provide a fast and
      definitive termination of bleeding or a resolution of acute ischemia. This
      approach, with its low invasiveness, can be proposed as first-line treatment in
      patients with traumatic lesions of upper-extremity arteries.

PMID- 21195900
TI  - Transarterial chemoembolization of a colic branch of the superior mesenteric
      artery in patients with unresectable hepatocellular carcinoma.
AB  - PURPOSE: To evaluate the technical feasibility, safety, and imaging response of
      transarterial chemoembolization performed through a colic branch of the superior
      mesenteric artery (SMA) in patients with hepatocellular carcinoma (HCC).
      MATERIALS AND METHODS: Between July 2000 and June 2009, we observed tumor
      staining supplied by a colic branch of the SMA in 61 of 5,095 patients (1.2%)
      with HCC. Computed tomography (CT) scans and digital subtraction angiograms of
      these patients were retrospectively reviewed by two investigators in consensus to
      evaluate the tumor location, the technical success of chemoembolization,
      complications, and imaging response on a follow-up CT scan according to European
      Association for the Study of the Liver criteria. RESULTS: Tumors supplied by a
      colic branch of the SMA were located in segment VI (n = 58) or were extrahepatic
      metastases caused by peritoneal seeding (n = 3). Vessels supplying the tumor
      arose from the right colic artery (n = 23), middle colic artery (n = 22), or
      ileocolic artery (n = 26). Selective chemoembolization via a colic branch of the
      SMA was performed in 24 patients (39%). No patient developed symptoms related to
      colon ischemia. Complete response or partial response of the tumor fed by a colic
      branch of the SMA as depicted on follow-up CT was achieved in eight patients
      (33%). CONCLUSIONS: Chemoembolization via a colic branch of the SMA can be safely
      performed if the microcatheter can be advanced beyond the antimesenteric border
      of the colon.

PMID- 21195902
TI  - Endovascular interventions of juxtaanastomotic stenoses and thromboses of
      hemodialysis arteriovenous fistulas: some overlooked inaccuracies.

PMID- 21195903
TI  - Percutaneous closure of an aorto-right ventricular fistula with an Amplatzer
      plug.

PMID- 21195904
TI  - Re: toward an optimal position for inferior vena cava filters: computational
      modeling of the impact of renal vein inflow with the Celect and TrapEase Filters.

PMID- 21195906
TI  - An unusual giant pseudoaneurysm with proximal and distal necks bypassing an
      occluded midsuperficial femoral artery.

PMID- 21195907
TI  - Renal nutrition: progress on fast track.

PMID- 21195908
TI  - Fighting protein-energy wasting in chronic kidney disease: a challenge of
      complexity.
AB  - Chronic uremia is often characterized by wasting of muscle and fat mass, which
      has been defined as protein-energy wasting (PEW), and is responsible for
      substantial worsening of patient outcome in terms of morbidity and mortality,
      mostly from cardiovascular events. Despite major advances in patient treatment,
      nutritional outcome in patients with end-stage renal disease has not improved
      substantially in recent years. Extensive research in this field has provided
      plausible explanations for this limitation by indicating that the pathogenesis of
      PEW in kidney disease is complex and multifactorial. Complexity involves
      underlying metabolic alterations, including inflammation, oxidative stress, and
      insulin resistance. In addition, patient heterogeneity is increasing with large
      numbers of obese individuals as a result of the ongoing obesity epidemics.
      Several tissues are involved in cross-talk and contribute to metabolic
      derangements, including adipose tissue, the gut, and the central nervous system,
      with novel mediators including the gastric hormone ghrelin. Acknowledging its
      complex pathogenesis may favor the development of novel and more effective
      therapeutic tools for PEW. These should ideally be effective in treating the
      underlying common mechanisms of wasting, which appear to include oxidative
      stress, inflammation, and insulin resistance.

PMID- 21195909
TI  - Mechanisms of altered regulation of food intake in chronic kidney disease.
AB  - Patients with chronic kidney disease (CKD) frequently experience loss of appetite
      (anorexia), which increases in severity during disease progression. The optimal
      management of patients with CKD and overt anorexia depends on an appropriate
      understanding of the causes of anorexia that are related to advanced CKD. This
      review aims to provide an overview of the multifactorial mechanisms concurrently
      contributing to the high prevalence of anorexia in the uremic population with
      advanced CKD.

PMID- 21195910
TI  - Causes of poor appetite in patients on peritoneal dialysis.
AB  - Anorexia is common in patients with chronic kidney disease and is a main
      contributor to the high prevalence of protein-energy wasting in them. The
      peritoneal dialysis (PD) procedure may further impair appetite by causing
      abdominal discomfort and also through the absorption of the osmotic agent and
      other factors. An increased peritoneal solute transport rate has been linked to
      protein-energy wasting and also to the malnutrition, inflammation, and
      atherosclerosis syndrome, which has been associated to poor appetite and plays a
      role in most premature deaths in these patients. The pathogenesis of these
      associations is unclear. In this review, we discuss the effect of PD, in
      particular, PD solutions, inflammation, and increased peritoneal solute transport
      rate, on appetite. We also describe strategies to increase appetite in PD
      patients.

PMID- 21195911
TI  - Interventions to counteract anorexia in dialysis patients.
AB  - The treatment of anorexia in chronic hemodialysis patients is based on a
      therapeutic strategy which includes optimal dialysis dose (through daily or
      nocturnal dialysis), support of food intake (through nutritional counseling and
      oral nutritional supplements), counteractive action to anorexic agents (e.g.,
      inflammatory cytokines and low levels of branched chain amino acids), stimulation
      of appetite (ghrelin), and attention to associated symptoms (e.g., symptoms of
      depression and anxiety, fatigue, other comorbidities). However, the fact remains
      that the studies so far conducted are insufficient both in terms of number and
      quality to provide guidelines for clinical and research purposes. Randomized,
      controlled trials are needed in the future to define the best strategy to
      counteract anorexia in maintenance dialysis patients.

PMID- 21195912
TI  - Benefits in nutritional interventions in patients with CKD stage 3-4.
AB  - The efficacy and safety of protein-restricted diets in chronic kidney disease
      (CKD) is still a matter of debate. However, several studies have clearly
      demonstrated the beneficial effects of such diets on the outcome of patients with
      stage 3-4 CKD. This point has been confirmed by 4 recent studies. In 2009, a meta
      analysis showed that protein restriction significantly delayed the time to renal
      death with a substantial economic benefit for the health service. Although
      toxicity of urea has since long been considered as negligible, an experimental
      model in rats has shown a direct role of urea in the development of oxidative
      stress and insulin resistance, which are among the leading mechanisms of
      cardiovascular complications in CKD. These latter results confirm an interest in
      studying reduction in blood urea levels as observed in patients kept on a low
      protein diet (LPD) or on a supplemented very-low protein diet (SVLPD). A
      reduction in proteinuria, which is associated to a LPD, has the following
      prognostic value: the more important the reduction in proteinuria, slower is the
      decline in renal function. This effect, which is additive to the one of an
      angiotensin-converting enzyme inhibitor (ACEI), is higher with SVLPD than with
      conventional LPD. Safety of a reduced protein intake has been confirmed by the
      study on the long-term outcomes (11 years) of patients already on SVLPD. The
      difference between these results and those from the extended follow-up of the
      modification of diet in renal disease (MDRD) study, in which no recommendations
      were made after the completion of the trial, confirms the importance of a close
      nutritional survey of patients with CKD who are put on a protein-restricted diet.

PMID- 21195913
TI  - Multimodal approach to malnutrition in malnourished maintenance hemodialysis
      patients.
AB  - Chronic organ failures, including chronic kidney disease, cardiac failure, and
      chronic pulmonary disease, share a common phenotype which is characterized by a
      high prevalence of anorexia, inflammation, oxidative stress, insulin resistance,
      hypogonadism, and anemia. Because of the systemic dimension of organ failure,
      such a phenotype results in a decrease in body mass, in addition to alterations
      of body composition and abnormal muscle structure, metabolism, and performance.
      The response of both protein-energy wasting and muscle disease to nutritional
      support given alone was shown to be limited both in chronic kidney disease and
      chronic pulmonary disease. Data are needed to evaluate the effects of an
      integrated management taking into account the different factor of muscle
      anabolism: nutrition support, endurance exercise, and, in selected patients,
      other anabolic agents such as androgens and omega-3 fatty acids.

PMID- 21195914
TI  - Energy expenditure in chronic kidney disease patients.
AB  - OBJECTIVE: The assessment of energy expenditure in patients with chronic kidney
      disease (CKD) is a subject that has started to be investigated in the past 3
      decades. This review will focus on studies that have assessed the energy
      expenditure of CKD predialysis and dialysis patients. Till date, most studies on
      this subject have focused on the assessment of resting energy expenditure (REE).
      In this regard, the current published data have demonstrated that clinically
      stable nondialysed CKD patients have REE similar or slightly lower than that of
      age- and gender-matched healthy individuals. For dialyzed patients, in both
      hemodialysis and peritoneal dialysis, the results are indicative that the REE of
      these patients is similar to that of age- and gender-matched healthy controls.
      The investigation of REE in specific catabolic conditions, such as poorly
      controlled diabetes, hyperparathyroidism, and inflammation, has shown that the
      REE in these catabolic conditions is increased. Additionally, it has also been
      reported that the hemodialysis procedure per se is also capable of enhancing the
      energy expenditure. The energy expenditure for physical activity is also an
      important component of energy expenditure and has been scarcely investigated in
      patients with CKD. The few studies that have investigated energy expenditure for
      physical activity have shown values lower than that of healthy sedentary
      individuals. CONCLUSION: These results are highly suggestive that patients with
      CKD have a sedentary lifestyle. The effect of the present knowledge of energy
      expenditure on the energy requirements of the patients with CKD remains to be
      investigated in studies using gold standard methods for this purpose.

PMID- 21195915
TI  - Energy intake and energy expenditure profiles in peritoneal dialysis patients.
AB  - Protein-energy wasting is a highly prevalent complication in patients with end
      stage renal disease receiving peritoneal dialysis therapy, and it powerfully
      predicts clinical outcomes of these patients. The etiology is usually
      multifactorial. In this article, we aim to present the energy intake and energy
      expenditure profiles and review some of the important causes that have a negative
      effect on them in patients on peritoneal dialysis.

PMID- 21195916
TI  - Have recommended protein and phosphate intake recently changed in maintenance
      hemodialysis?
AB  - The protein requirements recommended by international guidelines are uncommonly
      met in many dialysis patients. Recent large scale epidemiological studies have
      shown that survival impairs only when protein intake decreases below 0.9 g/kg
      body weight/day, and patients survival is highest for a protein intake comprised
      between 1.0 and 1.4 g/kg body weight/day. In case of inflammation, protein intake
      is frequently decreased by anorexia, however artificial nutritional support
      (either orally or intravenously) is able to improve nutritional status.
      Concerning phosphate intake, whereas increasing protein intake will slightly
      augment serum phosphate, the strongly observed beneficial survival benefit
      largely overcomes the serum phosphate increase risk. Finally, new dialysis
      techniques and/or membranes should be adequately assessed for their consequences
      on patients' nutritional status since there is a theoretical risk of increased
      nutrient losses.

PMID- 21195917
TI  - Salivary glands: a new player in phosphorus metabolism.
AB  - In uremic patients, hyperphosphatemia is associated with cardiovascular
      calcification and increased cardiovascular mortality. Despite the use of
      phosphate binders and dietary phosphate limitation in addition to dialysis, only
      50% of dialysis patients achieve recommended serum phosphate levels. The
      identification of other approaches for serum phosphorus reduction is therefore
      necessary. We have approached this issue by taking into account the relationships
      between serum phosphate, kidney function, and saliva. Saliva was chosen because
      the anatomy and/or physiology of acini, the secretive units of salivary glands,
      shares similarities with that of the renal tubules. Salivary fluid contains
      electrolytes including phosphate that, when related with the amount of salivary
      secretion per day, raises the interest in identifying another possible approach
      for phosphorus removal in uremic patients. This article reports studies from our
      laboratory in the last 3 to 4 years, which have demonstrated a hyperphosphoric
      salivary content in patients with chronic renal failure and those with end-stage
      renal disease under chronic dialysis that, in patients with chronic renal
      failure, linearly correlates with serum phosphate in patients with chronic renal
      failure and negatively with GFR. The ingestion of the saliva and later its
      absorption in the intestinal tract starts a vicious circle between salivary
      phosphate secretion and fasting phosphate absorption, thereby worsening
      hyperphosphatemia. Therefore, salivary phosphate binding could be a useful
      approach to serum phosphate level reduction in dialysis patients. The reduction
      of salivary phosphate with the salivary phosphate binder, chitosan-loaded chewing
      gum, chewed during fasting periods, as an add-on to phosphate binders could lead
      to a better control of hyperphosphatemia, as demonstrated in our study, which
      confirms the importance of this approach.

PMID- 21195918
TI  - Dialysis strategies to improve growth in children with chronic kidney disease.
AB  - Despite major advances in the understanding and management of uremic growth
      failure, 35% to 50% of children with chronic kidney disease still grow up to
      become adults of small stature. The final adult height achieved is correlated
      with the height deficit recorded at the time of kidney transplantation. A degree
      of catch-up growth does occur after kidney transplantation in childhood, but it
      is often limited. Growth retardation in children with chronic kidney disease
      causes significant difficulties in their daily lives, often limiting psychosocial
      integration. Additionally, growth retardation is associated with a greater number
      of hospital admissions and an increased risk of mortality. Growth failure is the
      common endpoint of a variety of pathologies, including growth hormone resistance.
      In children on chronic dialysis, linear growth may be improved by ensuring that
      optimal clinical care is provided. This includes maximizing nutritional support
      (e.g., tube feeding in cases of anorexia) so as to prevent malnutrition. Further
      management options include the administration of recombinant human growth hormone
      (rhGH) treatment and the use of more frequent and intensive dialysis sessions,
      such as daily on-line hemodiafiltration, which combines increased dialysis
      convective flow with ultrapure dialysate, to limit cachexia.

PMID- 21195919
TI  - Evidence-based guidelines for the nutritional management of adult kidney
      transplant recipients.
AB  - OBJECTIVE: The present article summarizes the key recommendations of the evidence
      based guidelines developed for the nutritional management of adult kidney
      transplant recipients. BACKGROUND AND METHODS: Nutrition interventions play an
      important role in preventing and managing common health problems associated with
      renal transplantation such as obesity, hypertension, diabetes, and cardiovascular
      disease. Two sets of guidelines were developed by a working group of renal
      dietitians and nephrologists. They were subject to expert panel review, and
      public consultation by renal clinicians and consumers before final endorsement by
      2 authorities in Australia--Caring for Australasians with Renal Impairment (CARI)
      and Dietitians Association of Australia (DAA). Protocol and rigor of guideline
      development were previously described and published in the Journal of Renal
      Nutrition, 2009. RESULTS AND OUTCOMES: These guidelines address 13 priority
      topics identified by the renal community and complement each other with different
      emphasis, from research translation to day to day clinical practice
      recommendations. The published guidelines are available to the public through web
      access of CARI and DAA, and journal publications. Information includes the
      guidelines themselves with level of evidence stated, grading of recommendations,
      suggestions for clinical care, search strategy, background and summary of
      evidence, recommendations of other guidelines, practice recommendations,
      appendices of useful tools, and suggestions for audits and future research.
      CONCLUSIONS: Two sets of comprehensive evidence-based nutrition guidelines from
      CARI and DAA are now available to help improve health outcomes of adult kidney
      transplant recipients.

PMID- 21195920
TI  - Exercise as an anabolic intervention in patients with end-stage renal disease.
AB  - Muscle wasting and accompanying structural derangements leading to abnormalities
      in muscle function, exercise performance, and physical activity are common in
      patients with end-stage renal disease. Therefore, several studies have been
      performed examining the effects of exercise in this particular patient
      population. Most of the studies have assessed the effects of cardiopulmonary
      fitness training, whereas a few have examined the role of resistance (i.e.,
      strength) training. Despite the proven efficacy of resistance exercise as an
      anabolic intervention in the otherwise healthy elderly population and certain
      chronic disease states, recent studies in patients on maintenance hemodialysis
      have not been encouraging in terms of long-term improvements in markers of muscle
      mass. Preliminary studies indicated that a combination of simultaneous exercise
      and nutritional supplementation could augment the anabolic effects of exercise,
      at least in the acute setting. However, a recent randomized clinical trial failed
      to show further benefits of additional resistance exercise on long-term somatic
      protein accretion above and beyond nutritional supplementation alone. Further
      research is necessary to both understand the observed lack of obvious benefits
      and strategies to improve the exercise regimens in patients with end-stage renal
      disease.

PMID- 21195921
TI  - Exercise-induced biochemical modifications in muscle in chronic kidney disease:
      occult acidosis as a potential factor limiting the anabolic effect of exercise.
AB  - There is growing evidence that exercise may be beneficial in limiting or
      reversing problems related to chronic kidney disease (CKD); but exercise therapy
      has had limited success in increasing lean body mass, implying that metabolic
      abnormalities in muscle during CKD may limit the anabolic effectiveness of
      exercise. This short review summarizes evidence that exercise may result in a
      transient worsening of the pre-existing metabolic acidosis that occurs in these
      patients; a metabolic defect that may reverse the normal anabolic effects of
      exercise.

PMID- 21195922
TI  - Effect of intradialytic resistance band exercise on physical function in patients
      on maintenance hemodialysis: a pilot study.
AB  - Although physical activity is recommended in patients on maintenance hemodialysis
      (MHD), randomized controlled trials testing the effects of exercise in this
      population have given conflicting results. In general, aerobic exercises mostly
      failed to produce improvements in physical function, whereas resistance
      exercises, although less studied, appeared to be more promising. The use of
      sophisticated materials such as leg press and free weights may preclude
      widespread application of resistance training in patients on MHD. Simple and
      cheap elastic bands may thus be an attractive alternative. We tested the
      feasibility of a supervised intradialytic resistance band exercise training
      program, and its effects on physical function, in patients on MHD. A total of 11
      unselected adult patients on MHD from our center, aged 70 +/- 10.7 (mean +/-
      standard deviation) years, including 8 men and 3 women, accepted to follow the
      program under the supervision of qualified physiotherapists. Thirty-six exercise
      sessions of moderate intensity (twice a week, mean duration 40 minutes each,
      during 4.5 to 6 months), mainly involving leg muscles against an elastic
      resistance, were performed. The exercise program was well tolerated and all
      patients completed it. Statistically significant improvements were observed in
      the following tests: Tinetti test, 23.9 +/- 3.9 points before versus 25.7 +/- 3.5
      points after the program (P = .022); the Timed Up and Go test, 12.1 +/- 6.6
      versus 10 +/- 5.8 seconds (P = .0156). Improvements in the 6-minute walk distance
      and in the one-leg balance tests just failed to reach statistical significance.
      In this single-center pilot study, an intradialytic resistance band exercise
      program was feasible, well tolerated, and showed encouraging results on physical
      function.

PMID- 21195923
TI  - The effect of obesity on chronic kidney disease.
AB  - Overweightness and obesity are associated with many hemodynamic, structural, and
      histopathologic alterations in the kidney and with metabolic and biochemical
      changes that predispose to these abnormalities. Consequent to these disorders,
      these individuals are more likely to develop chronic kidney disease and end-stage
      renal failure. Overweight and obese people are more prone to develop albuminuria
      and, for at least some types of kidney disease, a greater amount of albuminuria
      and more rapid progression of renal failure. These individuals are more likely to
      develop diabetes mellitus and hypertension. Diabetic nephropathy, hypertensive
      nephrosclerosis, focal and segmental glomerulosclerosis, renal cell carcinoma,
      and urate and calcium oxalate urolithiasis are the more common kidney and
      urological diseases reported in obese people. Preliminary data indicate that many
      of the clinical and nephropathologic manifestations associated with obesity can
      be reversed or ameliorated with reductions in body fat induced by dietary energy
      restriction or surgical procedures that reduce intake and gastrointestinal
      absorption of calories.

PMID- 21195924
TI  - Human uremic plasma and not urea induces exuberant secretion of leptin in 3T3-L1
      adipocytes.
AB  - Chronic kidney disease (CKD) is frequently associated with malnutrition,
      anorexia, and hyperleptinemia. This study was designed to test the hypothesis
      that a component of the uremic milieu may trigger leptin release by adipocytes.
      To this end, mouse 3T3-L1 adipocytes were incubated for 16 hours in culture
      medium containing urea (80 mM) or plasma from either healthy volunteers or
      patients with CKD (20%, v/v). Uremic plasma and not urea induced a large release
      of leptin (+557%, P < .01). These results suggest that the hyperleptinemia
      reported in patients with CKD, could be, at least in part, because of an
      overproduction of leptin by the adipose tissue.

PMID- 21195925
TI  - Body composition modifications in patients under low protein diets.
AB  - OBJECTIVE: To review the effect of low protein diets on body composition in
      patients with chronic kidney disease. METHODS: A selected literature review of
      body composition methods applicable to clinical practice, and a chronological
      appraisal of relevant studies using low and very low protein diets chosen for
      their major emphasis on nutritional status and body composition were used for the
      present study. RESULTS: Body composition methods were categorized by
      compartments, techniques, ease of use, clinical applicability, advantages, and
      disadvantages. One publication of body composition in chronic undernutrition was
      evaluated because of the absence of kidney disease as a confounder. The remaining
      studies covered chronic kidney disease stages III-V treated with low and very low
      protein diets. CONCLUSIONS: Very low protein diets are capable of sustaining mean
      lean and body cell mass for an extended period in patients with chronic kidney
      disease stages late III-V. However, intercurrent illness and periods of
      spontaneous reduction in caloric and protein intake markedly increase the risk
      for malnutrition. Use of these diets requires regular clinical monitoring by
      nephrologists and renal dietitians, with particular attention to nutritional
      surveillance, dietary protein and energy intake, and body composition changes.

PMID- 21195926
TI  - Adiponectin in chronic kidney disease: a complex and context sensitive clinical
      situation.
AB  - Although hyperadiponectinemia is a common phenomenon in chronic kidney disease
      and is considered to have similar beneficial effects on metabolic risk in this
      patient group, many recent studies in general population have unexpectedly shown
      that high, rather than low, concentrations predict mortality. However, the
      apparent unfavorable effect of high adiponectin might not necessarily be
      exclusively or partially related to a direct effect of adiponectin, but rather it
      could be a consequence of a concurrent process of wasting (or pathogenic pathways
      linked to the wasting process) which may increase adiponectin levels. It is also
      possible that elevated circulating adiponectin levels mirror a state of volume
      and salt overload because natriuretic peptides and high salt intake were recently
      shown to stimulate secretion of adiponectin. Until nutritional and
      pharmacological treatment strategies that increase adiponectin in uremic patients
      can be advocated nephrologists have an important task to unravel the observed
      paradoxes.

PMID- 21195927
TI  - Adiponectin and leptin in chronic kidney disease: causal factors or mere risk
      markers?
AB  - Experimental and clinical evidence implicates the 2 major adipose tissue
      cytokines, adiponectin (ADPN) and leptin (LEP), in renal damage. The
      interpretation of the link between these cytokines and renal outcomes is strictly
      context-sensitive. Albuminuria is a feature of renal disease in the ADPN null
      mouse and this alteration can be reversed by supplementing ADPN. Accordingly, in
      young normoalbuminuric obese individuals low ADPN is associated with higher
      albumin excretion rate. Conversely, high ADPN is associated with more severe
      proteinuria in chronic kidney disease patients, possibly underlying a protective
      response aimed at countering the high renal and cardiovascular risk of high
      proteinuria. LEP administration ameliorates insulin resistance in insulin
      resistant patients with hereditary lipodystrophy--a disease characterized by
      severe LEP deficiency and renal disease--and the same intervention reverses both,
      insulin resistance and renal damage in a mouse model of LEP deficiency. However,
      LEP may exert noxious effects on the kidney (particularly renal fibrosis) if
      administered in conditions of LEP sufficiency or excess.

PMID- 21195928
TI  - Sequence of cellular events in pancreatic islets leading to impaired insulin
      secretion in chronic kidney disease.
AB  - OBJECTIVES: In chronic renal failure (CRF), a multitude of metabolic derangements
      occur in the pancreatic islets, resulting in impaired glucose-induced insulin
      secretion. These abnormalities include a rise in the basal level of cytosolic
      calcium ([Ca(2+)]i) in the islets, a decrease in their basal and stimulated
      adenosine triphosphate (ATP) and adenosine diphosphate (ADP) content, a reduction
      in the V(max) of Ca(2+) ATPase and Na(+)-K(+) ATPase, and an impaired glucose
      induced calcium signal. The sequence of events that leads to these derangements
      and to the impairment in insulin secretion during the evolution of CRF has not
      been defined. This study examined this particular issue by measuring the
      metabolic profiles of pancreatic islets weekly during the evolution of CRF over a
      period of 6 weeks. RESULTS: The results showed that serum levels of parathyroid
      hormone (PTH) begin to rise during the first week of CRF. The V(max) of Ca(2+)
      ATPase and Na(+)-K(+) ATPase increased during weeks 1 to 3 of CRF but decreased
      to low levels thereafter. At week 3 of CRF, the basal level of [Ca(2+)]i began to
      rise, whereas basal and stimulated ATP and ADP content started to fall. Glucose
      induced calcium signal, Delta[Ca(2+)]i, and insulin secretion became abnormally
      low between weeks 3 and 6 of CRF. CONCLUSION: The data obtained allow for the
      inference of the following formulation: as serum levels of PTH begin to rise,
      calcium entry into islets is augmented, which in turn will stimulate the activity
      of Ca(2+) ATPase and the Na(+)-Ca(2+) exchanger, and therefore, calcium extrusion
      out of the islets is increased. Thus, [Ca(2+)]i remains normal during the first 2
      weeks of CRF. Activation of the Na(+)-Ca(2+) exchanger may result in accumulation
      of sodium in the islets, an event that would activate the Na(+)-K(+) ATPase.
      Because calcium entry is further augmented by the progressive rise in serum PTH
      levels, mitochondrial oxidation and ATP production would be reduced, resulting in
      lower ATP content. This fall in ATP causes a reduction in the V(max) of Ca(2+)
      ATPase and Na(+)-K(+) ATPase, and therefore calcium extrusion out of the islets
      is reduced; consequently, [Ca(2+)]i rises. With the decrease in ATP content and
      the rise in [Ca(2+)]i, glucose-induced insulin secretion is impaired because of
      alterations in the closure of ATP-dependent potassium channels and reduction in
      the glucose-induced calcium signal (Delta[Ca(2+)])i.

PMID- 21195929
TI  - Insights into nutritional and inflammatory aspects of low parathyroid hormone in
      dialysis patients.
AB  - In individuals with advanced chronic kidney disease, secondary
      hyperparathyroidism is known to be associated with high turnover bone disease.
      Low serum parathyroid hormone (PTH) levels may not necessarily be because of
      hypodynamic bone, but could be another facet of the malnutrition-inflammation
      cachexia syndrome (MICS). A recent 5-year cohort study in 748 stable hemodialysis
      outpatients showed that after the confounding effect by the MICS was removed, the
      moderately low levels of PTH in the 100 to 150 pg/mL range was associated with
      the greatest survival rate. Data from Japanese dialysis patients show similar
      survival advantages of having a lower PTH range. Low levels of serum PTH seem to
      be associated with markers of protein-energy wasting and inflammation, and this
      association may confound the relationship between serum PTH and alkaline
      phosphatase. PTH stimulates lipogenesis through influx of calcium into the
      adipocytes. PTH secretion is suppressed by interleukin-1 beta and interleukin-6,
      which are proinflammatory cytokines that are associated with poor outcome in
      dialysis patients. These cytokines inhibits PTH secretion in cultured parathyroid
      tissue slices. In this article, we review the association of a low serum PTH
      level with the MICS in patients with chronic kidney disease and suggest avoiding
      over-interpretation of low serum PTH level as an indicator of low turnover bone
      disease.

PMID- 21195930
TI  - Indoxyl sulfate reduces klotho expression and promotes senescence in the kidneys
      of hypertensive rats.
AB  - BACKGROUND: Administration of indoxyl sulfate, a uremic toxin, promotes
      progression of chronic kidney disease in rats affected by the disease. Klotho, an
      anti-aging gene, is expressed in the kidneys, and its renal expression is
      decreased in chronic kidney disease. This study aimed to clarify whether indoxyl
      sulfate could reduce klotho expression and contribute to cell senescence in the
      kidneys of hypertensive rats. METHODS: The rats used for this study were
      segregated in to the following 4 groups: (1) Dahl salt-resistant normotensive
      rats (DN), (2) Dahl salt-resistant normotensive indoxyl sulfate-administered rats
      (DN + IS), (3) Dahl salt-sensitive hypertensive rats (DH), and (4) Dahl salt
      sensitive hypertensive indoxyl sulfate-administered rats (DH + IS). After 32
      weeks, their kidneys were excised for histological and immunohistochemical
      analysis for klotho, senescence-associated beta-galactosidase, p16(INK4a),
      p21(WAF1/CIP1), p53, and retinoblastoma protein (Rb). RESULTS: DH + IS rats
      showed decreased expression of klotho, increased expression of senescence
      associated beta-galactosidase, p16(INK4a), p21(WAF1/CIP1), p53, and Rb in renal
      tubular cells, and increased tubulointerstitial fibrosis and mesangial expansion
      as compared with DH rats. Further, DN + IS rats showed decreased expression of
      klotho as compared with DN rats. CONCLUSION: Administration of indoxyl sulfate to
      hypertensive rats reduced renal expression of klotho and promoted cell senescence
      with expression of senescence-related proteins, such as p16(INK4a),
      p21(WAF1/CIP1), p53, and Rb, which was accompanied by renal fibrosis.

PMID- 21195931
TI  - New insight on vitamin C in patients with chronic kidney disease.
AB  - Patients on dialysis often develop anemia, which is accompanied by the
      development of substantial iron stores after administration of intravenous iron.
      This can be remedied in some instances with administration of supplemental
      vitamin C, either intravenously or orally. This is because of the mobilization of
      stored iron, which results in correction of anemia and in improvement of iron
      indices of red cells and reticulocytes. The short red cell survival often seen in
      patients on dialysis creates a situation in which very large amounts of iron are
      needed to be supplied for new erythropoiesis, and vitamin C therefore contributes
      to necessary iron delivery. The safety of this therapy needs careful study so as
      to determine vitamin C dosage that is effective and also avoids complications of
      oxalosis.

PMID- 21195932
TI  - Vitamin D biology: from the discovery to its significance in chronic kidney
      disease.
AB  - Vitamin D was discovered and had its chemical structure described in the early
      years of the last century. Although classified as a nutrient because it was found
      in small quantities in butter, it soon became clear that exposure of skin to
      sunlight, supplies most of the vitamin D necessary for good health in human
      beings. Vitamin D (D3 or cholecalciferol) synthesis in the skin is extremely
      rapid and remarkably robust despite the complexity of the mechanisms involved.
      However, a number of factors related to latitude location, season, and skin
      characteristics can interfere with the photoproduction of vitamin D. The 2 forms
      of vitamin D (D3 or D2-ergocalciferol) are biologically inactive and require
      activation in the liver and kidney. The product of the first hydroxylation of
      vitamin D in the liver, 25-hydroxyvitamin D (25(OH)D), is the marker of vitamin D
      status. Hypovitaminosis D (serum 25(OH)D, <30 ng/mL) is highly prevalent in the
      general population, and patients with chronic kidney disease seem to be at higher
      risk for the development of hypovitaminosis D. It is believed that, besides the
      traditional factors, protein losses, gastrointestinal malabsorption, and
      defective skin synthesis of vitamin D might contribute to the elevated number of
      patients with suboptimal level of vitamin D status.

PMID- 21195933
TI  - Guidelines for vitamin supplements in chronic kidney disease patients: what is
      the evidence?
AB  - Wide discrepancies exist in the use of vitamins in kidney disease, and evidence
      based recommendations are sparse. Water-soluble vitamin levels may be inadequate
      in patients not receiving supplements and this may be associated with increased
      mortality, which deserves further attention to increase strength of evidence.
      Supplements should be administered cautiously as renal mechanisms to prevent
      hypervitaminosis are no longer functional. The most reliable assays for vitamin
      status examine tissue mechanisms that rely on vitamins as cofactors. Vitamin A
      levels are generally quite high, vitamin D is low and requires supplementation,
      and the benefits of vitamin E may be linked to its usage in a modified dialysis
      membrane. Because of restricted diets that provide limited vitamin intake from
      food, many renal patients can benefit from a tablet that adds an amount equal to
      one recommended daily allowance of water-soluble vitamins, but larger amounts are
      not appropriate or beneficial. Vitamin status is influenced by interaction of
      many variables, and individual attention to each patient is warranted to achieve
      optimal vitamin status.

PMID- 21195934
TI  - New insights into lipid metabolism in chronic kidney disease.
AB  - Disorders in lipid levels in kidney disease consist of alterations both in the
      levels of the differing lipoprotein classes as well as alteration in their
      structures. Triglycerides (TGs) are increased, and both high density lipoprotein
      (HDL) and low density lipoprotein (LDL) levels are reduced. HDL fails to mature
      normally primarily as a consequence of decreased activity of lecithin cholesterol
      ester transfer protein (LCAT), and HDL levels are reduced because of increase
      clearance. The HDL that is present consist of small pre-beta discoid HDL that
      fails to function as an antioxidant. All of the apo B containing lipoproteins
      exhibit decreased clearance in part because of increased levels of the
      lipoprotein lipase inhibitory apolipoproteins apo C I and apo C III. The
      concentration of oxidized LD, an athorgenic risk factor, is increased, in part
      because of the inability of the HDL that is present to reduce oxidized LDL and in
      part because of the increased LDL residence time effected by decreased clearance.

PMID- 21195935
TI  - Serum uric acid as a new player in the development of diabetic nephropathy.
AB  - The pathogenesis of diabetic nephropathy is complex and still not fully
      elucidated. Uric acid has been associated with renal disease, even though
      hyperuricemia may be a marker of or by itself be responsible for microvascular
      disease in diabetes. In animal models, elevated level of uric acid can lead to
      arteriolopathy of preglomerular vessels, impaired autoregulation, glomerular
      hypertension, as well as endothelial dysfunction. Kidney damage in hyperuricemic
      rats is not dependent on blood pressure, and instead involves the renin
      angiotensin system. In patients with diabetes, serum uric acid early in the
      course of diabetes is significantly, and independent of confounders, associated
      with later development of persistent macroalbuminuria. Therefore, uric acid may
      be a novel and important player in the pathogenesis of microvascular
      complications in diabetes. A dose-response relationship between serum uric acid
      and early decline in renal function has recently been demonstrated in patients
      with type-1 diabetes. Randomized controlled trials on drugs that lower uric acid
      need to be conducted to evaluate the causal relationship between serum uric acid
      and development and progression of diabetic kidney disease; in addition, large
      scale long-term treatment trials need to be performed, as they are still lacking.

PMID- 21195936
TI  - Metabolic syndrome and the genesis of uric acid stones.
AB  - Uric acid stones are significantly more common among nephrolithiasis patients
      with type 2 diabetes, obesity, and/or the metabolic syndrome. The principal
      metabolic feature responsible for this association is an overly acidic urine,
      which leads to the precipitation of sparingly soluble uric acid crystals in urine
      and subsequent development of stones. The unduly acidic urine in uric acid stone
      formers is caused by a combination of excessive dietary intake of animal proteins
      and a defect in renal ammoniagenesis and/or excretion that leads to impaired
      buffering and amplifies the acidic urine caused by an increased acid excretion.

PMID- 21195937
TI  - On the cover.

PMID- 21195938
TI  - Penicillin skin testing in the evaluation and management of penicillin allergy.
AB  - OBJECTIVE: to review the role of penicillin skin testing in the evaluation and
      management of penicillin allergy mediated by IgE. DATA SOURCES: PubMed and OVID
      search of English-language articles regarding penicillin allergy, penicillin
      allergy testing, and management of penicillin allergy. STUDY SELECTION: articles
      pertinent to the subject matter were selected and reviewed. RESULTS: the major
      determinant (benzylpenicillin polylysine) detects the greatest number of
      penicillin allergic patients during skin testing, and the minor determinants of
      penicillin increase the sensitivity of penicillin skin testing. Penicillin skin
      testing to the major and minor determinants was found to have a negative
      predictive value of 97% to 99%. The incidence of systemic adverse reaction to
      penicillin skin testing is less than 1%. CONCLUSION: a detailed history of the
      prior reaction to penicillin is an integral part of the evaluation, but it is not
      accurate in predicting a positive penicillin skin test result. A patient with a
      negative penicillin skin test result to the major and minor determinants is at a
      low risk of an immediate-type hypersensitivity reaction to penicillin. Patients
      with a positive skin test result should undergo desensitization to penicillin or
      an alternative antibiotic should be considered.

PMID- 21195939
TI  - Administering influenza vaccine to egg allergic recipients: a focused practice
      parameter update.

PMID- 21195941
TI  - Effect of age on asthma control: results from the National Asthma Survey.
AB  - BACKGROUND: two million US citizens older than 65 years have asthma, but little
      is known about asthma control in this population. OBJECTIVE: to compared short-
      and long-term asthma control in elderly (>= 65 years old) and young adult (18-64
      years old) populations from the National Asthma Survey. METHODS: data from the
      National Asthma Survey (sponsored by the Centers for Disease Control and
      Prevention) were analyzed. Demographic variables, health insurance status,
      smoking status, indoor allergen exposure, and asthma education were compared
      between the young adult and elderly populations. Asthma control was examined
      based on short-term measures (recent oral corticosteroid bursts or symptoms) and
      long-term measures (asthma attacks, urgent care visits, hospitalizations, and
      activity limitation in the previous year). RESULTS: a total of 2,557 young and
      398 elderly asthmatic patients were included. Elderly patients had a lower
      income, were less educated, were more obese, were more insured, had less indoor
      exposure, and were more likely to be former smokers. They were less educated
      about asthma attack interventions and asthma action plans (P < .05 for both). On
      multivariate analysis, elderly patients had worse control of asthma based on
      short-term measures (daytime symptoms in the previous month [odds ratio (OR),
      1.73; 95% confidence interval (CI), 1.25-2.35] and any short-term measure [OR,
      1.48; 95% CI, 1.11-1.97]) and long-term measures (activity limitation in the
      previous year [OR, 1.50; 95% CI, 1.12-2.01]). CONCLUSIONS: elderly asthmatic
      patients have worse short- and long-term asthma control compared with the young
      adult population. Further studies are needed to elucidate whether these findings
      are due to pathophysiologic differences and whether tailored education or other
      novel strategies can provide better asthma control.

PMID- 21195940
TI  - Relationship of asthma management, socioeconomic status, and medication insurance
      characteristics to exacerbation frequency in children with asthma.
AB  - BACKGROUND: less than 25% of asthmatic children are well controlled. OBJECTIVE:
      to identify factors associated with asthma exacerbation causing emergency
      department (ED) visits or hospitalizations related to health status,
      socioeconomic status (SES), and drug insurance. METHODS: in this retrospective
      cohort study, complete data were collected on 490 asthmatic children regarding
      demographics, SES, drug plan characteristics, health status, health resource use,
      and symptoms. Interview data were linked to administrative data on asthma ED
      visits and hospitalizations occurring in the following year. Multiple Poisson
      regression identified independent variables associated with ED visits or
      hospitalizations in the full cohort and in a subgroup with prescription drug
      insurance. RESULTS: younger age, previous emergency visits, nebulizer use, pet
      ownership, and receipt of asthma education but not an action plan were
      significantly associated with more frequent exacerbations. In the full cohort,
      children with high income adequacy had 28% fewer exacerbations than did children
      with low income adequacy. In the subgroup with drug insurance, girls had 26%
      fewer exacerbations than did boys, and children with food, drug, or insect
      allergies had 52% more exacerbations than did children without allergies.
      Children of families with annual insurance deductibles greater than $90 had 95%
      fewer exacerbations. Every percentage increase in the proportion of income spent
      out-of-pocket on asthma medications was associated with a 14% increase in
      exacerbations. CONCLUSIONS: asthma history, disease management factors, and SES
      were associated with exacerbations requiring urgent care. In families with drug
      plans, the magnitude of asthma medication cost-sharing as a proportion of
      household income, rather than income alone, was significantly associated with
      exacerbations.

PMID- 21195942
TI  - Impact of obesity in asthma: evidence from a large prospective disease management
      study.
AB  - BACKGROUND: asthma and obesity continue to have a significant effect on public
      health. It is widely accepted that obesity may be an independent risk factor for
      asthma and affect asthma severity and quality of life (QOL). OBJECTIVE: to
      examine the relationship between body mass index (BMI [calculated as weight in
      kilograms divided by height in meters squared]) and asthma severity, spirometry
      findings, health care utilization (HCU), and QOL. METHODS: this 12-month
      prospective randomized controlled trial comparing disease management with
      traditional care enrolled 902 patients (473 pediatric and 429 adults)
      representing an underserved population. Data collected at baseline and at 6-month
      intervals included demographics, asthma severity, medication use, spirometry
      findings, and HCU. The QOL was assessed using the pediatric and adult versions of
      the Asthma Quality of Life Questionnaire and the 36-Item Short Form Health
      Survey. All HCU was determined by means of patient interview and extensive
      medical record review. Data were analyzed using negative binomial regression and
      analysis of variance. RESULTS: in children, 45% were overweight/obese (17% with
      BMIs >85th percentile; 28% with BMIs >= 95th percentile). In adults, 58% were
      obese (BMIs >= 30). There was no relationship in children between BMI and
      severity of asthma, spirometry findings, QOL, or HCU. In adults, there was no
      relationship between BMI and asthma severity or HCU. Higher BMI was associated
      with a significant reduction in QOL (P < .001). The BMI had an inverse
      relationship with forced vital capacity but with no other spirometric values.
      CONCLUSIONS: obesity was not associated with worse asthma severity, spirometry
      findings, QOL, or HCU in children. In adults with asthma, obesity was associated
      with lower forced vital capacity and QOL but not with severity or HCU.

PMID- 21195943
TI  - Bronchial hyperresponsiveness to methacholine and adenosine monophosphate and the
      degree of atopy in children with allergic rhinitis.
AB  - BACKGROUND: nonasthmatic patients with allergic rhinitis often have bronchial
      hyperresponsiveness (BHR). Not only the presence but also the degree of atopy are
      important factors in BHR of patients with asthma. BHR is commonly evaluated by
      bronchial challenges using direct or indirect stimuli. OBJECTIVES: to assess BHR
      to methacholine (direct) and to adenosine monophosphate (AMP) (indirect) in
      children with allergic rhinitis and to compare their relationships with the
      degree of atopy. METHODS: methacholine and AMP challenges were performed in 88
      children with allergic rhinitis, and a provocative concentration causing a 20%
      decrease in forced expiratory volume in 1 second (PC(20)) was calculated for each
      challenge. The degree of atopy was measured using serum total IgE levels, number
      of positive skin prick test results, and atopic scores (sum of graded wheal
      size). RESULTS: BHR to methacholine (PC(20) <8 mg/mL) and to AMP (PC(20) <200
      mg/mL) was observed in 22 (25%) and 30 (34%) patients, respectively. No
      association was found between BHR to methacholine and any atopy parameter. In
      contrast, serum total IgE levels and atopic scores were higher in the group with
      BHR to AMP than in the group without BHR to AMP. Furthermore, a significant
      association was found between the degree of these 2 parameters and BHR to AMP
      (score for trend, P < .001 and P = .03, respectively). CONCLUSIONS: both BHR to
      methacholine and BHR to AMP were detected in a significant proportion of children
      with allergic rhinitis. The degree of atopy seems to be an important factor in
      BHR to AMP but not in BHR to methacholine.

PMID- 21195945
TI  - The REPEAT study: recognizing and evaluating periodic local reactions in allergen
      immunotherapy and associated systemic reactions.
AB  - BACKGROUND: prior studies have demonstrated that large local reactions (LLRs) to
      subcutaneous immunotherapy do not predict systemic reactions (SRs). However, a
      recent study demonstrated an increase in LLRs among systemic reactors in
      practices using routine local reaction dose adjustments. OBJECTIVE: to
      investigate the association between LLRs and SRs within a practice that does not
      dose adjust for LLRs. METHODS: we performed a retrospective analysis of an
      electronic immunotherapy database during a 12-month period at a single site that
      does not dose adjust for LLRs. An LLR was defined as larger than the size of the
      patient's palm measured at 30 minutes. Logistic regression was performed to
      investigate the association between SRs and LLRs after controlling for variable
      numbers of injections and visits among patients. RESULTS: three hundred sixty
      patients received a total of 9,679 injections (6,609 visits). Twenty-four
      patients (6.7% of patients) experienced 38 LLRs (0.4% of injections, 0.6% of
      visits), whereas 46 patients (12.7% of patients) experienced 51 SRs (0.5% of
      injections, 0.77% of visits). Only 10 patients (2.8%) experienced both LLRs and
      SRs, and 36 of 46 SR patients (78.3%) never had an LLR. Among the 24 LLR
      patients, the SR rate was 1.3% (12/932) of injections and 2.0% (12/611) of visits
      compared with the 336 non-LLR patients for whom the SR rate was 0.4% (39/8,747)
      of injections and 0.7% (39/5998) of visits. Of these 24 LLR patients, 10 (41.7%)
      experienced at least 1 SR vs 36 of 336 non-LLR patients (10.7%). After
      controlling for number of injections and 1 vs 2 injections per visit, a subgroup
      of LLR patients were more likely to have an SR during their subcutaneous
      immunotherapy course (odds ratio, 4.7; 95% confidence interval, 1.9-11.7).
      Recurrent LLR patients (n = 10) were not more likely to experience an SR (0.4%
      per injection). CONCLUSIONS: although LLRs do not predict SRs, a subgroup (41.7%)
      of LLR patients experience a higher frequency of SRs during their immunotherapy
      course. In light of a similar previous study, this association occurs
      irrespective of whether a dose adjustment protocol is used for LLRs.

PMID- 21195944
TI  - Predictors of hospital admission for food-related allergic reactions that present
      to the emergency department.
AB  - BACKGROUND: guidelines do not provide specific hospitalization criteria for
      patients presenting to the emergency department (ED) with food-related allergic
      reactions. OBJECTIVE: to determine predictors of hospital admission for ED
      patients with food-related allergic reactions. METHODS: we performed a medical
      record review at 3 academic centers of patients presenting to the ED for food
      related allergic reactions (International Classification of Diseases, Ninth
      Revision, Clinical Modification codes 693.1, 995.0, 995.1, 995.3, 995.7, 995.60
      995.69, 558.3, 692.5, and 708.X) between January 1, 2001, and December 31, 2006.
      We focused on patient demographics, medical history, food triggers, clinical
      presentation, pre-ED and ED management with a specific focus on epinephrine
      treatment, and disposition. Predictors of hospital admission were determined
      using multivariable logistic regression. RESULTS: through random sampling and
      appropriate weighting, the 1,112 cases reviewed represented a study cohort of
      2,583 patients. Most patients (80%) were discharged from the ED. The age and sex
      of patients admitted to the hospital and those discharged were similar.
      Multivariable analysis identified 3 factors associated with a higher likelihood
      of hospital admission: meeting the criteria for food-related anaphylaxis (odds
      ratio [OR], 2.31; 95% confidence interval [CI], 1.23-4.33), pre-ED epinephrine
      treatment (OR, 6.65; 95% CI, 3.04-14.57), and epinephrine treatment within 1 hour
      of ED triage (OR, 3.78; 95% CI, 1.68-8.50). Patients with food-related allergic
      reactions triggered by shellfish were less likely to be admitted to the hospital
      (OR, 0.23; 95% CI, 0.08-0.68). CONCLUSIONS: most patients presenting to the ED
      with food-related allergic reactions are discharged. Several patient factors were
      independently associated with hospital admission in ED patients with food-related
      allergic reactions.

PMID- 21195946
TI  - Inhibitory effect of Platycodon grandiflorum on T(H)1 and T(H)2 immune responses
      in a murine model of 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin
      lesions.
AB  - BACKGROUND: Platycodon grandiflorum is a traditional Asian medicine that is used
      to treat pulmonary and respiratory allergic disorders. OBJECTIVE: to investigate
      the effects of P grandiflorum in vivo in an animal model of atopic dermatitis
      (AD), with particular emphasis on its effects on T(H)1 and T(H)2 immune
      responses. METHODS: we established a model of AD-like skin lesions in NC/Nga
      mice. After oral administration of P grandiflorum, we measured cytokine and
      immunoglobulin profiles along with histologic examination of skin. RESULTS: P
      grandiflorum was nontoxic in a 2,4-dinitrofluorobenzene-induced model of AD-like
      skin lesions in NC/Nga mice. AD symptoms in skin lesions improved after oral
      administration of P grandiflorum. IgE secretion was significantly downregulated
      in P grandiflorum-treated animals, accompanied by decreased levels of interleukin
      (IL) 4 and IgG1 and increased serum levels of IL-12p40 and IgG2a. In isolated
      splenocytes, the production of the T(H)1 cytokines IL-12p40 and interferon-gamma
      was upregulated by P grandiflorum, whereas the levels of the T(H)2 cytokines IL-4
      and IL-5 were downregulated in a mouse model of AD-like skin lesions.
      CONCLUSIONS: these results suggest that P grandiflorum inhibits the development
      of AD-like skin lesions in NC/Nga mice by suppressing the T(H)2 cell response and
      increasing the T(H)1 cell responses. Our results indicate that P grandiflorum is
      safe and effective as a natural herbal medicine for the treatment of AD-like skin
      lesions.

PMID- 21195947
TI  - Prospective study of C1 esterase inhibitor in the treatment of successive acute
      abdominal and facial hereditary angioedema attacks.
AB  - BACKGROUND: hereditary angioedema (HAE) is a rare disorder characterized by a
      quantitative or functional deficiency of C1 esterase inhibitor (C1-INH),
      resulting in periodic attacks of acute edema at various body locations. The
      symptoms of these painful attacks can be treated effectively with C1-INH
      concentrate. OBJECTIVE: to document the efficacy and safety of a weight-based
      dose of C1-INH concentrate in the treatment of successive HAE attacks at
      abdominal and facial locations. METHODS: acute facial and abdominal attacks were
      each treated with C1-INH concentrate using a single intravenous dose of 20 U/kg
      body weight. Efficacy end points included patient-reported time to onset of
      symptom relief and time to complete resolution of all symptoms. Safety was
      assessed by monitoring adverse events and assaying for markers of viral
      infection. RESULTS: we treated 663 abdominal attacks in 50 patients and 43 facial
      attacks in 16 patients (a total of 706 attacks in 53 patients). The median time
      to onset of relief for all attacks was 19.8 minutes, with a median time to
      complete resolution of 11.0 hours. The median time to onset of relief was 19.8
      minutes for abdominal attacks and 28.2 minutes for facial attacks, indicating
      efficacy for both types of attack. No treatment-related serious adverse events
      occurred, and C1-INH concentrate was well tolerated. No human immunodeficiency
      virus, hepatitis virus, or parvovirus B19 infections arose during the study.
      CONCLUSION: the C1-INH concentrate dose of 20 U/kg provides rapid, effective, and
      safe treatment for successive HAE attacks at abdominal and facial locations.

PMID- 21195948
TI  - Proposed pathobiologic mechanisms of hypoxia-ischemia-reperfusion in
      corticosteroid-resistant neutrophilic asthma and consideration of interleukin 1
      targeted therapy.

PMID- 21195949
TI  - Eosinophilic esophagitis after specific oral tolerance induction for egg protein.

PMID- 21195950
TI  - Comparison of doubling and quadrupling methacholine concentration regimens using
      the tidal volume method.

PMID- 21195951
TI  - Bacteriostatic agents and sterility requirements for allergen immunotherapy.

PMID- 21195952
TI  - Management of laparoscopic bladder injuries.

PMID- 21195953
TI  - Bilateral herniation of the ovaries into the anterior compartment of the pelvis.

PMID- 21195954
TI  - Unabsorbed intraabdominal polylactide adhesion barrier.

PMID- 21195955
TI  - Ultrasound and ovarian cancer screening: is there a future?
AB  - Ovarian cancer is a leading cause of death due to gynecologic malignant disease.
      Advances in ultrasound have improved the ability to identify the more subtle
      characteristics of adnexal masses, resulting in an increasing volume of research
      addressing its use to accurately predict whether masses are benign or malignant,
      and the inclusion of ultrasound in large-scale studies addressing screening for
      ovarian cancer. Herein, we explore some of the factors that make screening for
      ovarian cancer challenging, review the major trials addressing the effect of
      ovarian cancer screening, and examine data relating to more recent advances in
      ultrasound technology.

PMID- 21195956
TI  - Use of a pessary in treatment of pelvic organ prolapse: quality of life,
      compliance, and failure at 1-year follow-up.
AB  - STUDY OBJECTIVES: To estimate the effect of pessary use on symptom improvement
      and quality of life in women with pelvic organ prolapse, to examine factors that
      influence patient choice and continued use of a pessary, and to determine reasons
      associated with discontinuation of pessary use. DESIGN: Retrospective study
      (Canadian Task Force classification II-3). SETTING: Outpatient urogynecologic
      clinic of a university hospital. PATIENTS: Seventy-two patients with symptomatic
      pelvic organ prolapse were evaluated for pessary insertion between March 2006 and
      August 2008. INTERVENTIONS: Insertion of a Gellhorn pessary. MEASUREMENTS AND
      MAIN RESULTS: Urinary symptoms and quality of life were assessed using the
      Urinary Distress Inventory incontinence questionnaire (UDI-6) and the
      Incontinence Impact Questionnaire (IIQ-7) at baseline and postinsertionally at 2
      months and at 1 year. Frequency of choosing pessary use or surgery and rate of
      continuous use of a pessary was compared between groups. Compared with baseline
      findings, at 1 year, UDI-6 and IIQ-7 demonstrated significant improvement in
      frequency of micturition, stress incontinence, voiding function, and bowel
      evacuation. Substantially more older or menopausal women opted for a pessary
      rather than surgery, and significantly more sexually active women preferred
      surgery. Women with diabetes mellitus or occult stress urinary incontinence and
      those without family support are more likely to discontinue pessary use.
      CONCLUSIONS: Use of a pessary in treatment of pelvic organ prolapse is associated
      with good compliance, and results in significant improvement in quality of life
      and urinary and bowel symptoms. Women with diabetes or occult stress urinary
      incontinence and those without family support should receive intensive counseling
      before placement of a pessary.

PMID- 21195957
TI  - The levonorgestrel intrauterine system is an effective treatment in selected
      obese women with abnormal uterine bleeding.
AB  - OBJECTIVE: To evaluate the use of the levonorgestrel intrauterine system (LNG
      IUS) in obese premenopausal women with abnormal uterine bleeding (AUB). DESIGN:
      Prospective observational study (Canadian Task Force Classification II-2).
      SETTING: University-affiliated teaching hospital. PATIENTS: Fifty-six obese women
      with body mass index (BMI) >30 kg/m(2). INTERVENTIONS: From January 2002 through
      September 2009, 56 obese patients (BMI >30 kg/m(2)) with abnormal uterine
      bleeding (AUB) were identified from the senior author's clinical practice
      (G.A.V.). After clinical assessment, including Papanicolaou smear, endometrial
      biopsy, and pelvic sonography, the LNG-IUS was placed to treat their AUB.
      MEASUREMENTS AND MAIN RESULTS: The median and (range) for age, parity, and BMI
      were 42.5 years (20-64), 2 children (0-6), and 41.2 kg/m(2) (30-61),
      respectively. Many patients had additional comorbid conditions placing them at
      high risk for traditional medical or surgical therapies. The initial endometrial
      biopsy result was normal in 46 women (82.1%). Three women (5.4%) had inadequate
      sample, three (5.4%) had simple endometrial hyperplasia, two (3.6%) had complex
      endometrial hyperplasia without atypia, and two women (3.6%) had complex
      endometrial hyperplasia with atypia. After placement of the LNG-IUS, all women
      reported menstrual blood reduction at 3 and 6 months. The LNG-IUS was expelled in
      2/56 patients (3.6%) and removed in 12 (21.4%), and a new device was inserted in
      3/56 patients (5.4%). At median follow-up of 48 months (range 3-72), the
      satisfaction rate was 75%. CONCLUSION: In properly selected obese women with AUB,
      the LNG-IUS is an effective therapy in approximately 75% of cases.

PMID- 21195958
TI  - Laparoscopic hysterectomy: impact of uterine size.
AB  - OBJECTIVE: To analyze surgical results of women having Type VII laparoscopic
      hysterectomy to determine whether differences in outcomes exist on the basis of
      uterine size. METHODS: This is an analysis of data from 983 cases of type VII
      laparoscopic hysterectomy performed from September 1996 through August 2010.
      Demographic and surgical data were stratified by uterine weight (range 14-3,131
      g) less than 250 g (n = 720) and 250 g or more (n = 263). Analyses were done by
      Pearson's chi(2), Wilcoxon rank-sum, and Kruskal-Wallis tests with significance
      set at 2-sided (p <.05). Outcomes examined include estimated blood loss, skin-to
      skin operative time, complications (non-reoperative and reoperative), and
      duration of hospital stay. Estimated blood loss, skin-to-skin operative time, and
      length of hospital stay were further analyzed using backwards, stepwise,
      multivariable, linear regression to control for and identify independent
      predictors affecting these outcomes. Baseline demographic data were included in
      the multivariable model. Only covariates that were significant in both
      multivariable and univariable analyses are presented as statistically
      significant. DESIGN: A case-controlled, retrospective study (Canadian Task Force
      Classification II-2). RESULTS: Median operating time varied by uterine weight,
      with a shorter duration of surgery in patients with uteri less than 250 g at 97
      minutes (range 29-330), and patients with uteri greater than 250 g at 135 minutes
      (range 45-345) (p <.001). Median estimated blood loss was also less in patients
      with uteri less than 250 g at 50 mL, (range 0-1400), than in patients with uteri
      weighing 250 g or more, at 150 mL, (range 0-2100) (p <.001). There was no
      significant difference by uterine weight in median duration of hospital stay of 1
      day (range 0-13), total complication rate (7.0%), reoperative complications
      (3.7%), or non-reoperative complications (3.4%). Duration of surgery, volume of
      blood lost, and length of hospital stay all decreased with the surgeon's
      increasing experience. CONCLUSIONS: Laparoscopic hysterectomy is feasible and
      safe, resulting in a short hospital stay, minimal blood loss, minimal operating
      time, and few complications for patients regardless of uterine weight.

PMID- 21195959
TI  - Pathologic characteristics of hysterectomy specimens in women undergoing
      hysterectomy after global endometrial ablation.
AB  - STUDY OBJECTIVE: To describe uterine pathologic features in women who underwent
      hysterectomy because of failed global endometrial ablation (GEA). DESIGN:
      Retrospective cohort study from 1998 through 2005 (Canadian Task Force
      classification III). SETTING: Tertiary referral center. PATIENTS: Sixty-nine
      women who underwent hysterectomy because of GEA failure. INTERVENTIONS: Pathology
      reports were available for 67 patients. Descriptions of hysterectomy specimens
      after GEA were reviewed. MEASUREMENTS AND MAIN RESULTS: Rates of pathologic
      findings in hysterectomy specimens after failed GEA were determined. Reasons for
      hysterectomy in the 67 patients with available pathology reports were bleeding in
      34 (51%), pain in 19 (28%), and bleeding and pain in 14 (21%). The pathology
      reports of these specimens showed leiomyomas in 33 specimens (49%); intramural
      myomas were present in 15 women (44%) who underwent hysterectomy because of
      bleeding and 8 women (42%) who underwent hysterectomy because of pain.
      Hematometra was identified in 7 pathologic specimens (10%). Specifically,
      hematometra was identified in specimens from 5 of 19 women who underwent
      hysterectomy because of pain (26%). CONCLUSION: Hematometra was a significant
      finding in women who underwent hysterectomy because of persistent pain after GEA.
      A possible pathologic predictor of GEA failure may be intramural leiomyomas.

PMID- 21195960
TI  - Operative hysteroscopy to remove retained products of conception: novel treatment
      of an old problem.
AB  - STUDY OBJECTIVE: To assess the efficacy and reproductive outcome of hysteroscopic
      removal of retained products of conception. DESIGN: Retrospective analysis
      (Canadian Task Force classification II-3). SETTING: Tertiary care university
      hospital. PATIENTS: One hundred fifty-nine patients were consecutively admitted
      to our department from July 2001 through August 2007 with a diagnosis of retained
      products of conception after medical abortion, dilation and evacuation, or
      delivery. INTERVENTIONS: Hysteroscopic removal of retained products of conception
      without the use of electrical energy. MEASUREMENTS AND MAIN RESULTS: Complete
      evacuation of the uterus was achieved in all patients. Trophoblastic tissue was
      histologically confirmed in 88%. All of the women regained normal menstrual
      bleeding. Complications occurred in 3 patients during or immediately after the
      procedure: pulmonary edema, sepsis and diffuse intravascular coagulopathy, and
      excessive bleeding, respectively. Of the 28 women who expressed a desire to
      become pregnant, 23 conceived. The conception rate was 82% (23 of 28), with a
      live-birth rate of 75% (21 of 28). Second-look hysteroscopy performed in 21
      patients revealed no adhesions. CONCLUSION: Hysteroscopic removal of retained
      products of conception is a simple and safe, and most probably the preferred
      procedure. It should be considered an alternative to conventional blind
      evacuation by curettage. It seems that this procedure preserves the integrity of
      the uterine cavity while averting additional trauma, and retains reproductive
      capacity. Further studies, including randomized controlled trials, may be
      necessary to confirm these results.

PMID- 21195961
TI  - Diagnostic hysteroscopy using liquid distention medium: comparison of pain with
      warmed saline solution vs room-temperature saline solution.
AB  - STUDY OBJECTIVE: To compare pain intensity and degree of satisfaction reported by
      patients undergoing hysteroscopic examinations using saline solution kept at room
      temperature (control group) or saline solution heated to 37.5 degrees C (test
      group). DESIGN: Randomized, controlled, prospective study (Canadian Task Force
      Classification I). PATIENTS: Sixty-four women underwent diagnostic hysteroscopy
      during the second half of 2008. INTERVENTION: In both the test and control
      groups, examinations were performed using the vaginoscopy technique without use
      of a speculum or Pozzi tenaculum forceps. Pain was assessed using a visual analog
      scale immediately after the examination and at 1 and 15 minutes after the
      procedure. MEASUREMENTS AND MAIN RESULTS: Immediately after the examination, mean
      (SD; 95% confidence interval) pain intensity in the warmed saline solution group
      was 3.84 (2.71; 2.89-4.79), and in the room-temperature saline solution group was
      4.31 (3.02; 3.18-5.44) (p = .51). At 1 and 15 minutes after the procedure, pain
      intensity in the 2 groups was, respectively, 2.41 (2.00; 1.66-3.16) and 2.43
      (2.49; 1.57-3.30) (p = .96), and 1.83 (2.30; 1.02-2.64) and 1.85 (2.06; 1.08
      2.62) (p = .96). Differences were not significant. Time to complete the
      examination was 3.80 (1.32; 3.34-4.26) minutes in the test group, and 3.75 (1.10;
      3.34-4.15) minutes in the control group (p = .82). The satisfaction rate with the
      warmed distention medium was 84% (95% confidence interval, 72%-96%), and with the
      room-temperature saline solution was 85% (73%-97%) with saline at room
      temperature (p = .48). CONCLUSION: There was no statistically significant
      difference between the 2 groups insofar as pain, duration of the examination, and
      degree of patient satisfaction.

PMID- 21195962
TI  - Oral analgesia vs intravenous conscious sedation during Essure Micro-Insert
      sterilization procedure: randomized, double-blind, controlled trial.
AB  - STUDY OBJECTIVE: To compare the pain reported by patients during the Essure Micro
      Insert sterilization procedure using either intravenous conscious sedation or
      oral analgesia. DESIGN: Randomized, double-blind, placebo-controlled trial
      (Canadian Task Force classification I). SETTING: Tertiary care ambulatory women's
      clinic. PATIENTS: Eighty women of reproductive age women requesting permanent
      sterilization. INTERVENTION: Hysteroscopic placement of the Essure Micro-Insert
      permanent birth control system. MEASUREMENTS AND MAIN RESULTS: Patients
      undergoing placement of the Essure Micro-Insert system for permanent
      contraception were randomized to receive either intravenous conscious sedation,
      oral analgesia, or placebo. During the procedure, pain scores were recorded using
      a visual analog scale. Patients in the oral analgesia group reported slightly
      more pain during insertion of the hysteroscope and placement of the second micro
      insert; the groups were otherwise equivalent. They were also equivalent when all
      visual analog scale scores were combined. CONCLUSION: Oral analgesia is an
      effective method of pain control during placement of the Essure Micro-Insert
      permanent birth control system.

PMID- 21195963
TI  - Combined hysteroscopic findings and 3-dimensional reconstructed coronal view of
      the uterus to avoid laparoscopic assessment for inpatient hysteroscopic
      metroplasty: pilot study.
AB  - STUDY OBJECTIVE: To assess the use of 3-dimensional (3D) reconstructed coronal
      view of the uterus and intraoperative hysteroscopic findings to avoid diagnostic
      laparoscopy during inpatient hysteroscopic metroplasty. DESIGN: Pilot study
      (Canadian Task Force classification II). SETTING: University hospital infertility
      clinic. PATIENTS: Fifty-nine patients with recurrent abortion and double uterine
      cavity with 3D sonographic diagnosis of septate uterus undergoing inpatient
      hysteroscopic metroplasty. INTERVENTIONS: Inpatient hysteroscopic treatment of
      septate uterus without laparoscopic diagnosis. In addition to sonographic
      observations, 2 intraoperative hysteroscopic criteria were used to confirm the
      diagnosis: visualization of muscular fibers and myometrial blood vessels.
      MEASUREMENTS AND MAIN RESULTS: Operative parameters (operative time and fluid
      absorption), complications (incomplete resection and uterine perforation),
      requirement for a second intervention, and shape of the uterine cavity at
      hysteroscopic follow-up. In 56 of 59 patients (94.9%), intervention was performed
      without complications, and in 3 cases, intervention was suspended because of
      intraoperative suspicion of bicornate uterus. These 3 patients underwent
      laparoscopy, which confirmed the diagnosis of septate uterus. In all cases,
      incision was considered sufficient. Postoperative diagnostic hysteroscopy in all
      patients showed a normal cavity (fundal notch <1 cm). CONCLUSIONS: Combined use
      of hysteroscopic confirming criteria and 3D sonography seems to be a reliable and
      simple strategy for characterizing the presence of septate uterus and to perform
      inpatient metroplasty usually without laparoscopic visualization of the uterine
      fundus.

PMID- 21195964
TI  - Multiple bowel perforations requiring extensive bowel resection and hysterectomy
      after microwave endometrial ablation.
AB  - Heavy menstrual bleeding, or menorrhagia, is a primary cause of morbidity in
      women. Herein, we present the case of a 41-year-old woman who underwent day
      surgery endometrial microwave ablation because of dysfunctional uterine bleeding.
      She had undergone previous laparoscopic sterilization, and had no other risk
      factors except for a retroverted uterus. The procedure was performed without any
      documented difficulties. The patient was readmitted the following day with
      clinical signs of acute abdomen. Emergency laparotomy revealed a large
      perforation on the anterior uterine wall, full-thickness burns in the distal
      ileum, and multiple ischemic areas in the ileum, cecum, and ascending colon
      secondary to microwave burns. A right hemicolectomy was required, with extended
      ileal resection and subtotal hysterectomy with ovarian conservation. Although
      microwave endometrial therapy seems to offer many advantages, in particular in
      terms of efficiency and technique, complications occur, and extensive safety
      measures must be implemented to prevent adverse effects such as occurred in this
      patient.

PMID- 21195965
TI  - Neoadjuvant chemotherapy plus fertility-sparing surgery in locally advanced
      cervical cancer: case report.
AB  - Cervical carcinoma is the second most common malignant disease worldwide, often
      occurring in young women who have not completed childbearing. In this era of
      emphasis on conservative treatments, management of cervical cancer could be
      influenced by patient desire to preserve fertility, maintaining the uterine
      corpus. Herein is reported the case of a young woman with locally advanced
      cervical cancer that was successfully treated using neoadjuvant chemotherapy
      followed by simple vaginal trachelectomy and laparoscopic lymphadenectomy. The
      success of such an approach, which is not the standard of care in this disease,
      suggests that additional studies should be performed in a selected population.

PMID- 21195966
TI  - Ureter in histopathologic specimen: a gynecologist's nightmare.
AB  - An 18-year-old woman presented with a large right-sided ovarian cyst. After
      further evaluation and counselling, the patient underwent laparotomy and
      oophorectomy. The pathology report described a large mature cystic teratoma with
      a tubular structure consistent with a cross-section of ureter. Subsequent
      evaluation of the urinary tract system was normal indicating that the ureter was
      an element of the mature cystic teratoma.

PMID- 21195967
TI  - Epidermoid cyst of round ligament: case report and review of literature.
AB  - Round ligament tumors are rare, and when found are typically leiomyomas. Herein
      is described a case of an epidermoid cyst of the round ligament, previously
      reported only once in the literature. Epidermoid cysts are similar to dermoid
      tumors but have only an epidermis-lined structure filled with keratin. Management
      included laparoscopic removal of the tumor. The patient's recovery was
      uneventful.

PMID- 21195968
TI  - Resolution of catamenial epilepsy after goserelin therapy and oophorectomy: case
      report of presumed cerebral endometriosis.
AB  - Endometriosis can develop in every organ and tissue in the female body except
      perhaps the spleen. The mechanism of distal metastasis is thought to be
      hematogenous or lymphatic spread from the uterus. Endometriotic lesions in the
      central nervous system are rare. Herein, we report the case of a woman with
      abnormal uterine bleeding who developed catamenial neurologic signs and symptoms.
      Computed tomography scans and magnetic resonance images demonstrated a
      circumscribed lesion in the left centrum semiovale of the brain. All neurologic
      symptoms resolved completely after treatment with gonadotropin-releasing hormone
      agonist for 3 months and subsequent laparoscopic bilateral oophorectomy. The
      patient was thought to have cerebral endometriosis, a rare phenomenon, although
      several cases have been reported in the literature. Temporal association of
      neurologic signs and symptoms with menstruation that resolves with medical or
      surgical menopause is highly suggestive of cerebral endometriosis.

PMID- 21195969
TI  - Spontaneous vaginal expulsion of uterine myoma after magnetic resonance-guided
      focused ultrasound surgery.
AB  - Uterine myomas are common benign uterine tumors in women of reproductive age.
      Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a minimally
      invasive procedure that produces coagulative necrosis at a precise focal point
      within the body. MRgFUS regarded as an effective and safe treatment modality in
      women with symptomatic uterine myomas. Vaginal passage of treated myoma tissue
      has been reported during other therapeutic procedures such as uterine artery
      embolization or during puerperium. This study is the first to report a case of
      vaginal expulsion of uterine myoma after MRgFUS, with complete endometrial
      recovery on follow-up.

PMID- 21195970
TI  - Laparoscopic cystectomy of ovarian teratoma in anti-NMDAR encephalitis: 2 case
      reports.
AB  - We present 2 case reports of anti-N-methyl-d-aspartate receptor (NMDAR)
      encephalitis that was successfully treated via laparoscopic ovarian cystectomy.
      In both cases, resection of an ovarian teratoma resulted in eventual full
      recovery. Although adnexectomy has been reported for tumor resection in anti
      NMDAR encephalitis, we chose ovarian cystectomy to preserve ovarian function. The
      efficacy of cystectomy is equivalent to that of adnexectomy. This suggests that
      ovarian adnexectomy may not be necessary in anti-NMDAR encephalitis with ovarian
      teratoma.

PMID- 21195971
TI  - Time-related increase of staphylococci, Enterobacteriaceae and yeasts in the oral
      cavities of comatose patients.
AB  - BACKGROUND/PURPOSE: The composition of oral microbiota in comatose patients
      remains uncertain. Some pulmonary pathogens may be found in dental biofilms or as
      part of the saliva microbiota. It is supposed that some pneumopathogenic
      microorganisms may overgrow in the mouths of comatose patients and spread to
      their lungs. METHODS: The oral colonization dynamics of staphylococci,
      Enterobacteriaceae and yeasts in nine comatose patients (group 1), and in 12
      conscious patients that brushed their teeth at least twice a day (group 2) was
      evaluated. Both groups were followed up for 7 days after hospitalization. Daily
      samples of saliva were obtained, dispersed and plated on selective culture media
      and colony forming units of each microbial group were obtained. RESULTS: For
      patients in group 1, the counts of total viable bacteria, staphylococci,
      Enterobacteriaceae and yeasts progressively increased in a time-dependant manner.
      For the conscious patients of group 2, there was no increase. CONCLUSION: It
      would appear that concomitant consciousness and brushing teeth are determinants
      in controlling the selected pneumopathogen counts in resting saliva. The increase
      in microbial counts in comatose patients is understandable because these
      microorganisms could spread to the lungs.

PMID- 21195972
TI  - Spinal tuberculosis in non-HIV-infected patients: 10 year experience of a medical
      center in central Taiwan.
AB  - BACKGROUND/PURPOSE: Tuberculosis (TB) is an endemic disease in Taiwan and it
      usually affects the lung. Spinal TB accounts for 1-3% of all TB infections. The
      purpose of this study was to investigate the clinical manifestations, management,
      outcomes and drug susceptibility of Mycobacterium tuberculosis in non-HIV
      infected patients with spinal TB. METHODS: From January 1998 to December 2007, we
      retrospectively reviewed the medical charts of adult patients with a diagnosis of
      spinal TB. Only those with positive culture results and/or characteristic
      pathologic findings were enrolled. Demographic data, clinical manifestations and
      susceptibility to anti-TB drugs were reviewed and analyzed. RESULTS: During the
      study period, 38 patients (23 men, 15 women) with spinal TB were identified and
      the mean age was 68 years. The median duration of symptoms was 60 days (range, 3
      720 days). Amongst the 38 patients, back pain (100%) was the most common clinical
      symptom, followed by weakness (53%) and numbness (26%). The lumbar spine (15
      patients, 39%) was the most commonly involved site, followed by the thoracic
      spine (14 patients, 37%). Concomitant pulmonary TB was found in 12 patients
      (32%). Three patients (8%) had concurrent bacterial or fungal infections. Almost
      all of the patients (35 patients, 92%) were successfully treated with surgery and
      anti-TB medications. The erythrocyte sedimentation rate was followed up in 16
      patients before and after therapy and a significant decline was observed after
      treatment (p = 0.004). No mortality was related to spinal TB. CONCLUSION:
      Insidious clinical course and ambiguous manifestations of spinal TB often delay
      and hinder the accuracy of diagnosis of spinal TB. In addition to pyogenic
      osteomyelitis, spinal TB should be included in the differential diagnosis
      especially in elderly patients with chronic back pain accompanied by elevated
      erythrocyte sedimentation rate, and those living in the TB endemic area.

PMID- 21195973
TI  - Clinical characteristics and risk factors for mortality in patients with
      meningitis caused by Staphylococcus aureus and vancomycin minimal inhibitory
      concentrations against these isolates.
AB  - BACKGROUND/PURPOSE: Bacterial meningitis caused by Staphylococcus aureus is
      uncommon but has a high mortality rate. The aims of this study were to better
      understand the clinical manifestations of S. aureus meningitis, to identify the
      risk factors for mortality in the affected patients, and to determine the levels
      of vancomycin minimal inhibitory concentrations (MICs) against these pathogens.
      METHODS: A retrospective study of patients with S. aureus meningitis hospitalized
      between December 2000 and December 2008 was made, and vancomycin MICs against S.
      aureus isolates was determined using Etest. RESULTS: Among 37 patients with S.
      aureus meningitis, fever was most commonly observed. Twenty-six patients (70.3%)
      had received prior neurosurgery, and 24 (64.9%) patients were suffering from
      methicillin-resistant S. aureus (MRSA) infections. The vancomycin MIC of 2 MUg/mL
      was found in 23 (74.2%) of 31 S. aureus isolates available for testing. Excluding
      three patients who did not receive antibiotics for their S. aureus meningitis the
      mortality rate was 35.3% in the 34 remaining patients, with concurrent infective
      endocarditis an independent risk factor for mortality (odds ratio = 21.00; 95%
      confidence interval, 1.834-240.515; p = 0.01). CONCLUSION: Patients with S.
      aureus meningitis and concurrent infective endocarditis were at a higher risk of
      mortality. A vancomycin MIC of 2 MUg/mL against a substantial number of S. aureus
      isolates that grew from the cerebrospinal fluid suggests the importance of
      obtaining trough vancomycin concentrations of 15-20 MUg/mL for the treatment of
      MRSA meningitis.

PMID- 21195974
TI  - Staphylococcus lugdunensis infective endocarditis: a literature review and
      analysis of risk factors.
AB  - BACKGROUND/PURPOSE: Infective endocarditis caused by Staphylococcus lugdunensis
      is a rare disease. Since its first description in 1988, there have only been a
      few reports of this disease and the causative organism. These publications were
      primarily case reports and brief case series. We conducted a literature review to
      identify the nature of the disease and its risk factors. METHODS: We
      retrospectively reviewed the cases reported between 1988 and 2008 by searching
      the relevant literature using the keywords "endocarditis" and "Staphylococcus
      lugdunensis" in the Medline database. All cases included met the definition of
      the modified Duke criteria. RESULTS: For the period 1988-2008, 67 cases from 27
      articles were reviewed. The mean age of individuals was 53.9 years. Left-sided
      valvular endocarditis represented 52 (82.5%) of cases and native-valve
      endocarditis was evident in 48 (78.7%) of cases. A large proportion (82%) of 50
      S. lugdunensis strains were susceptible to penicillin. Valve replacement
      operations were performed in 42 (66.7%) patients and the mortality rate was
      38.8%. Univariate analysis showed a higher mortality rate in patients aged more
      than 50 years, those treated before 1995, those treated with antibiotics alone,
      and those with growth not detected by echocardiography. Medical treatment alone
      was the independent risk factor for mortality by multivariate analysis.
      CONCLUSION: S. lugdunensis endocarditis led to substantial morbidity and
      mortality. Detailed microbiological identification, echocardiography evaluation,
      and valve replacement may improve the clinical outcome of individuals with S.
      lugdunensis endocarditis.

PMID- 21195975
TI  - Epidemiology and clinical characteristics of Listeria monocytogenes bacteremia in
      a Taiwanese medical center.
AB  - BACKGROUND/PURPOSE: There have been many reported cases of Listeria monocytogenes
      bacteremia in Europe and the United States, but only a few from Taiwan. The
      present study was undertaken to analyze the clinical characteristics of patients
      with L. monocytogenes bacteremia in Taiwan. METHODS: Patients with culture
      confirmed L. monocytogenes bacteremia were identified at Chang Gung Memorial
      Hospital between January 2001 and December 2008. The clinical features and
      outcomes of the patients and the antimicrobial susceptibilities of the clinical
      isolates were analyzed. RESULTS: Forty-three patients, including two newborn
      babies (4.7%) and 41 adults (95.3%), with at least one episode of Listeria
      bacteremia were identified. Forty-two (97.7%) of these patients had underlying
      diseases. Thirty-three patients (76.7%) had fever, 14 (32.6%) had experienced
      respiratory distress, and 11 (25.6%) had reported changes in consciousness.
      Twelve patients died within 14 days of infection, corresponding to a case
      fatality rate of 27.9%. All the clinical isolates tested were susceptible to
      ampicillin, penicillin and vancomycin. CONCLUSION: Most cases of L. monocytogenes
      infection occurred in adults with underlying diseases, especially malignancy, and
      only two cases of neonatal L. monocytogenes bacteremia were identified over the 8
      year period. Penicillin, ampicillin and vancomycin could be used for the
      treatment of L. monocytogenes bacteremia, with the case-fatality rate lower for
      patients who received appropriate treatment.

PMID- 21195976
TI  - Invasive infections of Aggregatibacter (Actinobacillus) actinomycetemcomitans.
AB  - BACKGROUND/PURPOSE: Aggregatibacter (Actinobacillus) actinomycetemcomitans, part
      of the normal flora of the mouth, is frequently found in human periodontal
      cultures and is an important pathogen causing various invasive infections,
      particularly infective endocarditis. In this study, we describe the clinical
      course and outcome of patients with A. actinomycetemcomitans infection. METHODS:
      All patients suffering invasive A. actinomycetemcomitans infections at the
      National Taiwan University Hospital from January 1985 to December 2004 were
      included in this study. Relevant data regarding clinical presentation,
      antimicrobial treatment and outcome of these patients were analyzed. RESULTS:
      During the study period, there were 11 patients with invasive A.
      actinomycetemcomitans infections, including eight patients with infective
      endocarditis, one with osteonecrosis and two with pneumonia and chest wall
      lesions. Among the patients with infective endocarditis, four had prosthetic
      valve replacement, four suffered from rheumatic heart disease and one had
      undergone surgical repair of ventricular septal defect. Lesions in the oral
      cavity were the probable portals of entry of the microorganism, and included
      carious teeth, periodontitis or radiotherapy of the ear-nose-throat field, and
      were noted in nine patients. Transthoracic echocardiography and/or
      transesophageal echocardiography were performed on the patients with probable
      infective endocarditis but growth was demonstrated in only four of these
      patients. Blood culture yielded A. actinomycetemcomitans after prolonged
      incubation. Three isolates were resistant to penicillin and two of these were
      also resistant to ampicillin. CONCLUSION: The diagnosis of invasive A.
      actinomycetemcomitans infection was delayed due to the indolent clinical course,
      non-specific presentation and slow growth of the organism. Antibiotic therapy
      using amoxicillin/clavulanic acid, ampicillin, ampicillin/sulbactam, ceftriaxone,
      clindamycin, cefotaxime, or levofloxacin was successful in all patients. None of
      the patients demonstrated recurrence of infection 2-36 months following
      treatment.

PMID- 21195977
TI  - Clinical and microbiological characteristics of Chryseobacterium indologenes
      bacteremia.
AB  - BACKGROUND/PURPOSE: Reports detailing bacteremia caused by Chryseobacterium
      indologenes remain limited, with most cases reported in Taiwan. The clinical
      significance of C. indologenes has not been fully established. This retrospective
      study investigated the clinical features and antimicrobial susceptibility of C.
      indologenes bacteremia. METHODS: Patients with C. indologenes bacteremia were
      identified at a medical center/teaching hospital in northern Taiwan between
      January 1, 2004 and January 31, 2008. Clinical features and the antimicrobial
      susceptibilities of these patients were analyzed. RESULTS: Sixteen isolates of C.
      indologenes from 16 episodes in 16 patients were identified, with all patients
      having underlying diseases. Two patients (12.5%) had polymicrobial bacteremia.
      The portal of bacteremia was not determined in most cases. Other clinical
      syndromes included catheter-related bacteremia, urinary tract infection and
      peritonitis. The majority of patients had undergone invasive procedures. Other
      associated conditions included immunosuppression, neutropenia and prolonged use
      of antibiotics. Only three patients were treated with appropriate antibiotics
      according to minimum inhibitory concentrations. The susceptibilities of isolates
      to trimethoprim-sulfamethoxazole (75.0%), levofloxacin (62.5%), piperacillin
      tazobactam (50.0%), ciprofloxacin (43.75%) and cefepime (12.5%) were variable and
      the bacteremia-related mortality rate was 6.25%. CONCLUSION: C. indologenes
      isolates are resistant to multiple antibiotics, with newer fluoroquinolones and
      trimethoprim-sulfamethoxazole possibly representing the most appropriate
      antimicrobial agents to treat infections caused by this pathogen. However, the
      pathogenicity and factors of virulence for C. indologenes remain unclear, with
      our study revealing favorable outcomes of C. indologenes bacteremia.
      Epidemiological surveillance of this organism in Taiwan and extensive worldwide
      surveillance programs are required.

PMID- 21195978
TI  - Epidemiology and clinical peculiarities of norovirus and rotavirus infection in
      hospitalized young children with acute diarrhea in Taiwan, 2009.
AB  - BACKGROUND/PURPOSE: Acute diarrhea is one of the most common morbidities in
      pediatrics worldwide. We conducted a study to investigate the incidence of
      norovirus in young children hospitalized with acute diarrhea in Taiwan and its
      clinical peculiarity compared with rotavirus gastroenteritis. METHODS: Between
      January and December, 2009, patients younger than 5 years and admitted to
      hospital with acute diarrhea were randomly selected; and their stool samples were
      collected and tested for presence of rotavirus and norovirus by enzyme
      immunoassay and reverse transcription-polymerase chain reaction, respectively.
      The clinical manifestations and laboratory findings of the enrolled patients were
      analyzed. RESULTS: A total of 989 cases were enrolled with a mean age of 21.6 +/-
      13.7 months and a male proportion of 56.0%. Rotavirus and norovirus was detected
      in 20.2% and 14.6% of all patients, respectively. Genogroup II was the
      predominant strain of norovirus (80.6%). Children aged 6-36 months accounted for
      the majority of patients positive for rotavirus and norovirus (73.0% and 81.3%,
      respectively). The incidences of norovirus and rotavirus infection were higher
      during winter and early spring. Most patients with rotavirus and norovirus
      diarrhea experienced vomiting (74.9%vs. 74.8%, respectively) and fever (94.7%vs.
      71.3%, respectively). CONCLUSION: Most young diarrheal patients presenting with
      vomiting were likely to have norovirus or rotavirus infection. Patients with
      norovirus diarrhea experienced an absence of, or low-grade fever and longer
      duration of vomiting compared with those positive for rotavirus infection. A
      family history of current gastroenteritis may suggest the possibility of
      norovirus infection.

PMID- 21195979
TI  - Epidemic pleurodynia caused by coxsackievirus B3 at a medical center in northern
      Taiwan.
AB  - Epidemic pleurodynia is seldom reported in Southeast Asia and there has been no
      report from Taiwan. We conducted a retrospective chart review of children = 18
      years of age in the National Taiwan University Hospital from January 1 to
      December 31, 2005. Epidemic pleurodynia was defined as an acute illness
      characterized by sharp localized pain over the chest or upper abdomen. Patients
      with known heart diseases or pulmonary consolidations were excluded. In total, 28
      patients met the case definition of epidemic pleurodynia. Coxsackievirus B3 (CB3)
      was isolated in 15 (60%) of the 25 throat swab specimens. Four (14%) of the 28
      patients presented chest wall tenderness and only one (6%) of the 18 patients
      tested had an elevated creatinine kinase level. Twenty-one (75%) of the 28
      patients described pleuritic chest pains and 10 (45%) of the 22 chest
      radiographies exhibited pulmonary infiltrates or pleural effusions. Six patients
      were observed with tonsillar exudates and one was confirmed to have a CB3 urinary
      tract infection. The clinical features and radiological findings suggest that CB3
      associated epidemic pleurodynia might be a disease of the pleura and occasionally
      spreads to nearby tissues, resulting in chest wall myositis, pulmonary
      infiltrates and myopericarditis.

PMID- 21195981
TI  - Distribution of genes encoding resistance to macrolides, lincosamides and
      streptogramins among clinical staphylococcal isolates in a Turkish university
      hospital.
AB  - This study investigated the prevalence of genes encoding resistance to
      macrolides, lincosamides and streptogramins (MLS(B)) among staphylococci in a
      series of 301 erythromycin-resistant clinical isolates of Staphylococcus aureus
      and coagulase-negative staphylococci (CoNS). Erythromycin-resistance phenotypes
      were determined according to Clinical and Laboratory Standards Institute
      guidelines and specific resistance genes erm(A), erm(B), erm(C), msr(A) and
      msr(B) were identified using polymerase chain reaction. Two hundred of 301
      (66.5%) erythromycin-resistant staphylococcal isolates exhibited resistance to
      MLS(B) antibiotics. Of these, 127 (63.5%) exhibited a cMLS(B) resistance
      phenotype (resistant to both erythromycin and clindamycin), whereas 73 (36.5%)
      expressed the iMLS(B) resistance phenotype (resistant to erythromycin and
      susceptible to clindamycin). The most prevalent resistance determinants were
      erm(A) (62%) among S. aureus and erm(C) (30%) among CoNS isolates. Combinations
      of resistance mechanisms were rarely seen, and occurred most often in oxacillin
      resistant isolates. The results of the present study support the idea that there
      are geographical differences in the prevalence of erythromycin resistance
      mechanisms among staphylococci, therefore local surveillance studies are
      important tools for guiding therapy and in the promotion of judicious use of
      antimicrobial agents.

PMID- 21195980
TI  - Seroprevalence of hepatitis D virus and its risk factors in the west of Iran.
AB  - Despite the decreasing trend in hepatitis D virus (HDV) infection worldwide, the
      importance of this disease cannot be underestimated. The aim of this study was to
      evaluate patients positive for HBsAg with respect to HDV infection and related
      factors. Patients with chronic hepatitis B who presented at Hamedan Province
      Hepatitis Community Center in 2002-2007 were included. A questionnaire covering
      demographic variables and history of hepatic disease was completed for each
      patient. Necessary tests were performed and antibodies to HDV were measured using
      an enzyme-linked immunosorbent assay. Of 81 HBsAg positive patients, 14 (17.3%)
      contained anti-HDV IgG. Only one of the patients with anti-HDV IgM was positive
      for HBsAg. Of the anti-HDV IgG positive patients, two (14.3%) were women. Among
      the women examined in this study, 24 (35.8%) were anti-HDV IgG negative (p =
      0.21), and of these, six (42.8%) were HBeAg positive while 17 (25.4%) of the anti
      HDV IgG negative women were positive for HBeAg (p = 0.16). The prevalence of
      chronic hepatitis B among anti-HDV IgG positive and negative patients was 28.6%
      and 39.2% respectively (p = 0.31). Because of the relatively high rate of
      hepatitis B virus (HBV) and HDV co-infection in our study subjects, it is vital
      that healthcare providers and policy makers to recognize the risk factors
      associated with this HBV and HDV co-infection as well as the reasons for this
      increased anti-HDV serology in HBV carriers.

PMID- 21195982
TI  - Severe axillary lymphadenitis after BCG vaccination: alert for primary
      immunodeficiencies.
AB  - The bacilli Calmette-Guerin (BCG) vaccine is administered to all newborns in
      countries where tuberculosis is endemic. Immunocompromised hosts, namely patients
      with human immunodeficiency virus infection or primary immunodeficiencies, are
      especially prone to serious complications from this vaccine. We report three
      cases of BCG disease in children with primary immunodeficiencies: one with a
      partial recessive interferon-gamma receptor 1 deficiency, who developed BCG
      dissemination; and two relatives with ZAP70 deficiency, a severe combined
      immunodeficiency, both of whom presented with regional and distant BCG disease.
      All had severe axillary lymphadenitis. These clinical cases underline the
      importance of considering the diagnosis of immunodeficiency in a child with
      severe axillary lymphadenitis after BCG vaccination and of disseminated BCG
      disease in an immunodeficient child in the appropriate clinical setting.
      Moreover, BCG vaccination should be delayed in every newborn with a family
      history of primary immunodeficiency until the condition has been ruled out.

PMID- 21195983
TI  - Cerebral abscesses and septic pulmonary emboli due to Serratia marcescens
      infection arising from a Portacath.
AB  - Percutaneous intravenous devices are an essential component of modern health
      care. Although they are generally associated with a low incidence of vascular
      access device-related sepsis, the events following a vascular catheter-related
      sepsis can be clinically significant and difficult to treat. Here we report a
      case of Portacath-related sepsis with Serratia marcescens resulting in cerebral
      and pulmonary emboli, which in our knowledge, has not been reported before.
      Definitive identification and prolonged antimicrobial treatment according to
      culture sensitivities can lead to resolution of septic and pulmonary emboli.

PMID- 21195984
TI  - One step toward the development of preoperative risk index for postoperative
      reintubation after planned extubation in the operation room.

PMID- 21195985
TI  - Significant hypercapnia either in CO(2)-insufflated or air-insufflated
      colonoscopy under deep sedation.
AB  - BACKGROUND: previous reports showed that CO(2)-insufflated colonoscopy is safe
      and less discomfortable. However, hypercapnia remains a vital concernment if deep
      sedation is necessary for difficult colonoscopy with prolonged CO(2)
      insufflation. This observational study is to measure bodily CO(2) subjected to
      colonoscopy facilitated by CO(2)- and air- or air-insufflation in conscious
      sedation, deep-sedation and awake patients. OBJECTIVE: to investigate if CO(2)
      insufflated colonoscopy could increase the risk of hypercapnia in awake,
      conscious-sedation and deep-sedation patients. METHODS: 104 patients in our
      health center undergoing sequential esophagogastroscopy and colonoscopy screening
      were included. At patients' request, incremental intravenous sedatives were given
      in order that the air-insufflated esophagogastroscopy could be carried out
      without the molestation of gag and cough reflexes. The sedation levels were re
      evaluated before proceeding colonoscopy and the patients were divided into
      conscious-sedation (respond purposefully to verbal commands) and deep-sedation
      groups and randomly allocated for air or CO(2) insufflation. Transcutaneous
      capnography (TcCO(2)) was recorded every minute throughout the colonoscopy
      procedure. RESULTS: the baseline TcCO(2) in the air- (50.9 +/- 5.7 mmHg) and
      CO(2)-insufflated (53.1 +/- 6.5 mmHg) groups under deep sedation was
      significantly higher than the groups under conscious-sedation and the awake
      groups (p < 0.01). In both air- and CO(2)-insufflation groups there were also a
      statistically significant (p < 0.01) correlation in TcCO(2) between the start,
      the peak and the end of colonoscopy. TcCO(2) did not significantly change
      throughout the colonoscopy in awake and conscious-sedation groups, either with
      air or CO(2) insufflation. With deep sedation, TcCO(2) significantly increased
      and peaked around the time when the scope touching the cecum, and then returned
      to original state with suction and withdrawl of the colonoscope without
      significant interaction of CO(2) insufflation and deep sedation. CONCLUSION: the
      TcCO(2) during colonoscopy was correlated to the data before inserting
      colonoscope but significantly different within awake, conscious-sedation and deep
      sedation groups. TcCO(2) did not change significantly either with CO(2)
      insufflation or air insufflations in awake and conscious-sedation groups.
      However, in deep-sedation groups with significantly higher baseline TcCO(2),
      further increase of TcCO(2) were significant without interaction with CO(2)
      insufflation. We concluded that when patients need deep sedation for colonoscopic
      procedures facilitated by gas insufflation, hypercapnia is still considerably
      present, not only with CO(2) insufflation but also with air insufflation
      colonoscopy.

PMID- 21195986
TI  - Postoperative reintubation after planned extubation: a review of 137,866 general
      anesthetics from 2005 to 2007 in a Medical Center of Taiwan.
AB  - BACKGROUND: regarding general anesthesia, postoperative reintubation after
      planned extubation (RAP) is needed when circumstances compel us to do so,
      irrespective of prolongation of hospital stay and increase of medical
      expenditure. We describe here our implementation of a case-controlled model to
      identify the risk factors of RAP. METHODS: patients who saw RAP in the space from
      January 1, 2005 to December 31, 2007 were retrospectively sorted out from the
      Quality Assurance (QA) database of the Department of Anesthesiology. We compared
      RAP cases with the control group and analyzed the factors using descriptive
      statistics and logistic regression. Reintubation was defined as intubation after
      the extubation for the initial endotracheal intubation, for general anesthesia,
      at the time period before departure from the post-anesthesia care unit. RESULTS:
      of the 137,866 patients who underwent endotracheal intubation for general
      anesthesia, 83 (0.06%) sustained RAP. The control group included 249 patients
      randomly selected for endotracheal intubation without RAP. Twenty-two variables,
      including demographic, operative and anesthetic data, were analyzed. We found
      that patients with preoperative COPD (odds ratio: 7.17, 95% CI: 1.98-26.00),
      pneumonia (odds ratio: 7.94, 95% CI: 1.93-32.78), ascites (odds ratio: 13.76, 95%
      CI: 1.08-174.74) and systemic inflammatory response syndrome (SIRS) (odds ratio:
      11.90, 95% CI: 2.63-53.86) were more likely to be subjected to RAP. Airway
      surgery and head-neck surgery also predisposed patients to reintubation. However,
      administration of both an extra dose of opioid and neuromuscular blocker at the
      end of surgery proved irrelevant to RAP. CONCLUSIONS: risk factors for RAP are
      clear and unambiguous. This study will prompt further studies on preventative
      measures or evaluation of how to improve outcome.

PMID- 21195987
TI  - The relationship between night time snoring and cormack and lehane grading.
AB  - INTRODUCTION: airway management is one of the greatest concerns of
      anesthesiologists and difficult intubation, well known as the anesthesiologist's
      nightmare, is an event not easy to predict before induction of anesthesia. The
      aim of this study was to assess the relationship between history of snoring and
      the Cormack and Lehane grading score. MATERIALS AND METHODS: in a descriptive
      analytical study, 120 candidates for elective surgery were selected and allocated
      in the two groups (snoring and snoring free groups, respectively). The history of
      night time snoring was taken from the patient's wife/husband. After induction of
      anesthesia, each patient was assessed regarding the Cormack and Lehane grading
      under direct laryngoscopy. RESULTS: the difference between the two groups
      regarding Cormack and Lehane grading system was statistically significant.
      CONCLUSION: the findings of this study demonstrated a relationship between the
      presence of snoring and increased number of Cormack & Lehane grading score.

PMID- 21195988
TI  - Comparison of the efficacy of parecoxib versus ketorolac combined with morphine
      on patient-controlled analgesia for post-cesarean delivery pain management.
AB  - BACKGROUND: we compared the clinical efficacy and safety between a new injectable
      cyclooxygenase-2 selective inhibitor, parecoxib, and an old nonselective,
      ketorolac combined with morphine in patient-controlled analgesia (PCA) for
      management of post-cesarean delivery pain. METHODS: in this randomized, open
      label study, 66 parturients undergoing cesarean section were divided into two
      groups: In Group P the patients received an initial intravenous bolus of 40mg
      parecoxib as a loading dose post-operatively and then two bolus doses of 20mg
      parecoxib were subsequently given at intervals of 24h. Morphine was basically
      used in PCA manner during the 3-day study course; and in Group K patients
      received an intravenous loading bolus of 30mg ketorolac post-operatively and then
      90mg ketorolac combined with morphine in PCA fashion throughout the study course.
      Efficacy was evaluated by Verbal ranking scale (0-10) for pain intensity, Ramsay
      sedation score (1-6), profile of mood state (0-3) and quality of sleep (0-3), and
      patient satisfaction (0-4) with the analgesia. Efficacy evaluations and adverse
      effects were recorded every 24h and at 72h after initial loading boluses. The
      duration of hospital stay and total dose of morphine used throughout the study
      were also recorded. RESULTS: there were no significant differences of sedation
      scale, mood state, quality of sleep and satisfaction between two groups, except
      patients of Group P had a lower pain scores than those of the Group K at 24h
      (3.1, range 0-5 vs. 4.3, range 0-8, p = 0.005) and 72h (1.1, range 0-3 vs. 1.9,
      range 0-4, p = 0.005). Moreover, there were also no significant differences in
      the duration of hospital stay, but there was a lower total morphine requirement
      (22% reduction) in Group P in comparison with Group K (43.5 +/- 19.2 vs. 55.5 +/-
      21.5, p = 0.02). Regarding adverse effects, there were no statistical differences
      between two groups. CONCLUSIONS: we noted that parecoxib with PCA morphine can be
      used for post-cesarean delivery analgesia with the same efficacy as ketorolac for
      an opioid-sparing effect.

PMID- 21195989
TI  - New device for pentax-airway scope in pediatric intubation.
AB  - The PBLADE which is a component used with Pentax-Airway Scope (AWS) has only one
      size that is essentially for use in adults. It cannot be used in children and
      neonates. We have made a new device to fit the Pentax-AWS for use in children and
      neonates. This new device will provide a good indirect visualization for
      intubation in pediatric patients.

PMID- 21195990
TI  - Pentax-airway scope for tracheal intubation breaks through the limitation of neck
      motion in an ankylosing spondylitis patient wearing halo vest--a case report.
AB  - The Airway Scope (AWS) provides better glottic view than the conventional direct
      laryngoscopy in tracheal intubation. With it, the endotracheal tube can be more
      easily inserted into the tracheal lumen easily. We hereby presented a 24-year-old
      ankylosing spondylitis (AS) patient wearing a halo vest who was successfully
      intubated for undergoing cervical spine surgery involving C1 and C2 under general
      anesthesia. Pre-operative airway assessment revealed that he was a case of
      difficult intubation. An AWS was used for oral tracheal intubation which was
      achieved smoothly in the first attempt. AWS can be an alternative device for
      airway management in a patient wearing halo vest.

PMID- 21195991
TI  - Sudden transient paraplegia shortly after preoperative thoracic epidural
      catheterization--a case report.
AB  - We report a case of sudden onset of paraplegia shortly after thoracic epidural
      catheterization for postoperative analgesia and discuss the possible causes of
      this event. A 38-year-old woman was scheduled to receive right lobectomy of liver
      because of hepatocellular carcinoma. Thoracic epidural catheterization for
      postoperative analgesia was performed before the induction of anesthesia. After
      skin disinfection and local anesthetic skin infiltration with lidocaine, epidural
      catheterization through T(10-11) interspace was performed. Dural puncture without
      any neurological symptoms was noticed in the attempt and the epidural space was
      successfully identified through T(9-10) interspace in the second attempt.
      However, acute motor weakness and sensory impairment were met as the epidural
      catheter was being threaded into the epidural space. Magnetic resonance imaging
      (MRI) revealed no abnormal findings and the neurological deficits resolved
      spontaneously within 2h without any sequela. Finally, it was supposed that the
      transient neurological deficits were resultant from accidental subarachnoid
      injection of the local anesthetics used for skin infiltration. Preoperative image
      studies of the spine revealed a relatively short skin-to-dura distance either
      from median or paramedian approach, which might be the cause of the inadvertent
      intrathecal injection of local anesthetic during skin infiltration.

PMID- 21195992
TI  - Intraoperative wake-up test in a deaf-mute adolescent undergoing scoliosis
      surgery.
AB  - We present our experience in intraoperative wake-up test in a deaf-mute feminine
      teenager who underwent spine surgery for correction of lordoscoliosis. Inadequate
      comprehension of the preoperative instructions, together with higher threshold of
      arousal in deaf-mutism may possibly contribute to lingering of the test. The
      report implicated direct, painful stimulation of the tested limbs, rather than
      indirect cues, such as flap on the dorsum of hands would be required for
      performance of wake-up test in the deaf-mute patients.

PMID- 21195993
TI  - Perioperative transient ischemic attack caused by the cessation of warfarin.
AB  - This paper describes the circumstances of a patient who had been receiving long
      term warfarin treatment, but ceased it prior to surgical operation, sustained a
      transient ischemic heart attack post-operatively, which eventuated in delayed
      extubation and locked-in syndrome. For patients at low risk of perioperative
      bleeding, anticoagulation with oral vitamin K antagonist can probably be able to
      maintain the therapeutic range (INR <= 2.0) extreme. For patients with a high
      risk of bleeding, the international normalized ratio (INR) should be kept <= 1.5.
      Within this range, patients at low risk of thrombosis can discontinue warfarin
      treatment for 2-5 days pre-operatively; patients at high risk for thrombosis can
      stop warfarin but should probably be treated with intravenous or subcutaneous
      heparin when the INR is subtherapeutic.

PMID- 21195994
TI  - Coronary artery dissection in a patient with traumatic femoral shaft fracture.
AB  - We report a 24-year-old man who developed postoperative pulmonary edema and
      desaturation, after open reduction with internal fixation for left femoral shaft
      fracture sustained in a motorcycle accident. Cardiac catheterization revealed a
      left anterior descending coronary artery dissection. Review of his present
      history, showed that he neither had chest discomfort nor suffered from
      hemodynamic decompensation preoperatively. Only the abnormal 12-lead ECG with
      moderate tachycardia was suggestive of myocardial ischemia. Coronary artery
      dissection, although uncommon, is a disastrous complication following blunt chest
      trauma, and needs thorough preoperative evaluation to exclude its occurrence.

PMID- 21195995
TI  - Local anesthetic infiltration to the trachea facilitates spontaneous ventilation
      in a patient with giant lung bullae undergoing an emergent non-pulmonary surgery.

PMID- 21195996
TI  - [Hamartomatous polyp of the hypopharynx].
AB  - We present the clinical case of a polyp in the hypopharynx discovered
      incidentally while performing an upper digestive endoscopy in a middle aged
      woman. Endoscopic resection was performed, and the histological result was a
      hamartomatous polyp. We review the diagnosis and treatment of this rare entity.

PMID- 21195997
TI  - [Intraparotid aneurysm of the posterior communicating vein].

PMID- 21195998
TI  - [Laryngeal cancer in patients younger vs older than 40 years old: a matched
      paired analysis].
AB  - BACKGROUND: To compare clinical and demographic data between laryngeal cancer
      patients younger and older than 40 years old. METHODS: Is a matched-paired study,
      realized from 1989 to 2002. We selected 500 laryngeal cancer patients treated in
      the National Cancer Institute of Mexico. Fifteen cases of patients younger than
      40 years that accomplished inclusion criteria were identified, pair-matched and
      compared by clinical stage with 33 patients older than 40 years. We analyzed
      demographic factors and disease-free and Overall Survival by Kaplan-Meier method.
      RESULTS: We included 9 male and 6 female patients with a mean age of 34 years in
      contrast to a mean age of 62 years in the comparison group. Four cases in
      clinical stage I, none clinical stage II, 6 in stage III and 5 in stage IV were
      included in the younger group and compared to 8 patients in stage I, 15 in stage
      III and 10 in stage IV in the older group. No differences in demographic
      variables or lifestyle habits were found. All patients in stage I, are alive in
      both groups. Disease-free survival not show any differences when comparing stages
      III and IV (p=NS). Mean disease-free survival was 66 months and mean overall
      survival was 83 months in the younger group. CONCLUSION: Laryngeal carcinoma is
      rare in patients younger than 40 years. No gender, clinical or prognostic
      differences could be identified among the two groups. The prognosis of these
      patients seems to be only determined by the initial clinical stage.

PMID- 21195999
TI  - Graves' ophthalmopathy after total thyroidectomy for papillary carcinoma.
AB  - We report the case of a 53-year-old woman who underwent two-phase total
      thyroidectomy (June and December 2001) for a multinodular goiter with incidental
      discovery at the first procedure of a multicentric papillary carcinoma of the
      right thyroid lobe. Thyroidectomy was followed by an ablative dose of 131
      radioiodine because of the presence of residual tissue in the neck. The various
      elements of the follow-up are reassuring: no residual tissue was detected at the
      ultrasonography of the neck and thyroglobulin was undetectable in the absence of
      antithyroglobulin autoantibodies. In April 2006, the patient developed unilateral
      Graves' ophthalmopathy with the appearance of antithyrotropin receptor
      autoantibodies (TRAb). Ophthalmopathy progressively improved, in parallel to the
      decrease of TRAb. The parallel trend of TRAb and the ophthalmopathy supports the
      major role of TRAb in the pathogenesis of thyroid-associated ophthalmopathy. This
      observation also shows the possibility of developing autoantibodies in the
      absence of detectable thyroid tissue.

PMID- 21196000
TI  - Impact of diabetes mellitus on clinical presentation and prognosis of pancreatic
      cancer.
AB  - INTRODUCTION: The aim of this study was to investigate possible effects of
      diabetes mellitus on clinical manifestations and prognosis of pancreatic cancer
      (PC). PATIENTS AND METHODS: We retrospectively reviewed the clinical files of 122
      patients with PC, and divided them into two groups: those with diabetes (56
      patients) and those without diabetes (66 patients). The two groups were then
      compared for demographic profiles, clinical manifestations of PC, features of the
      tumor and fatal outcomes. RESULTS: Mean age, sex distribution, body mass index at
      cancer diagnosis, prevalence of hypertension, dyslipidemia, weight loss,
      abdominal pain, lumbar pain, signs of dyspepsia, and size, and histological
      features of the tumor were similar between the two groups. The cancer was located
      in the head of the pancreas in 50% of those with diabetes, and 80% of those
      without diabetes (P=0.04). The median survival time was similar. CONCLUSIONS:
      Clinical features, tumor size and prognosis of PC are similar in people with and
      without diabetes. Having diabetes does not seem to contribute to earlier
      diagnosis of PC.

PMID- 21196001
TI  - [Organization of the work from the consultations requested from the surgical
      services within the internal medicine departments].

PMID- 21196002
TI  - [Prevalence of metabolic syndrome in patients with stable coronary disease:
      therapeutic objectives and utilization of cardiovascular drugs].
AB  - OBJECTIVE: The achievement of the therapeutic objectives in patients with
      ischemic heart disease and metabolic syndrome is unknown. This study has aimed to
      evaluate whether the prevalence of risk factors, the prescription rate of
      evidence-based cardiovascular therapies and the attainment of therapeutic goals
      differ in coronary patients with and without the metabolic syndrome (MS).
      METHODS: A multicenter, cross-sectional study carried out with the participation
      of 7,600 patients with stable coronary heart disease (mean age 65.3 years, 82%
      males, 37.7% with MS) attended in primary care. Data on drug prescription and
      goal attainment were extracted from clinical records. MS was defined according to
      the National Cholesterol Education Program (NCEP) criteria. RESULTS: Patients
      with MS had a higher prevalence of cardiovascular risk factors and cardiovascular
      disease. They also had a higher prescription rate of blood-pressure lowering
      drugs, statins and antidiabetic agents, without differences in the rate of use of
      antithrombotics and beta-blockers. After adjusting for cardiovascular risk
      factors and co-morbidity, only fibrates and angiotensin II receptor blockers were
      used more frequently in MS patients. A lower percentage of subjects with MS
      achieved therapeutic goals of LDL cholesterol (23.4% vs 27.7%, P<.001), blood
      pressure (29.1% vs 52.2%, P<.001) and, in diabetics, of glycated hemoglobin
      (54.7% vs 75.9%, P<.001). CONCLUSION: Patients with stable coronary disease and
      MS do not reach therapeutic objectives as frequently as those without MS, in
      spite of receiving a higher amount of cardiovascular drugs.

PMID- 21196003
TI  - [Leukoencephalopathy followed by eclampsia].

PMID- 21196004
TI  - [Fever and dyspnea after laparoscopy cholecystectomy].

PMID- 21196005
TI  - The increasing burden of phlebotomy in the development of anaemia and need for
      blood transfusion amongst trauma patients.
AB  - BACKGROUND: Diagnostic laboratory tests are an integral part of the management of
      trauma patients, however, may be responsible for significant iatrogenic blood
      loss. The purpose of this study was to examine how phlebotomy practises have
      changed over time, and to assess the impact of these practises on patient
      outcomes. METHODS: A continuous series of injured patients admitted to a level I
      trauma centre (March-April 2004) was compared to the same period in 2009. All
      diagnostic tests and blood volumes withdrawn for each patient were tabulated.
      Primary outcomes were in-hospital mortality and length of stay (LOS); secondary
      outcomes were development of anaemia (Hgb<9 g/dl) and need for blood transfusion.
      A cost analysis was performed to determine the financial impact of the blood
      tests ordered. RESULTS: The 360 patients in 2009 and 384 patients in 2004
      demonstrated no significant differences in demographics or clinical data. When
      outcomes were compared, there were no significant differences in hospital LOS,
      ICU LOS or mortality. From 2004 to 2009, the mean number of laboratory tests per
      patient increased significantly (21.2+/-32.5 to 28.5+/-44.4, p=0.003). The total
      blood volumes drawn during the hospital stay also increased significantly
      (144.4+/-191.2 ml to 187.3+/-265.1 ml, p=0.025). For ICU patients (329.7+/-351.0
      ml to 435.9+/-346.3 ml, p=0.048). There was a 25% increase in costs due to
      laboratory blood tests over the study period. For ICU patients, a 36% increase in
      costs was observed. CONCLUSIONS: From 2004 to 2009, there was a significant
      increase in the utilisation of diagnostic laboratory tests in the management of
      the injured patient with no demonstrable improvements in mortality or LOS.
      Further prospective evaluation of these results is warranted.

PMID- 21196006
TI  - Increased carotid wall thickness measured by computed tomography is associated
      with the presence and severity of coronary artery calcium.
AB  - BACKGROUND: Previous studies have shown that increase in carotid wall thickness
      (CWT) is associated with cardiovascular risk factors. However, simultaneous
      systemic and local involvement of atherosclerosis in subjects with high risk of
      coronary atherosclerosis is not well studied. This study investigates the
      relation of carotid subclinical atherosclerosis assessed by CWT with the presence
      and severity of coronary artery calcium(CAC). METHODS: One hundred and twenty
      nine subjects (age of 69+/-10 years, 72% male) underwent CAC, carotid CT
      angiography, and their metabolic status was evaluated. CAC was defined as 0, 1
      100, 101-400, 401-1000 and 1000+. CWT (mm) was calculated as: [mean of both right
      and left CT-measured CWT 10-mm below the common carotid bifurcation]. RESULTS:
      Modest correlation between CWT and CAC was noted (r=0.48, p=0.0001). CWT
      increased substantially with the severity of CAC from CAC 0 to CAC 1000+
      (p<0.05). Increased CWT (1.0 mm+) was more prevalent in subjects with significant
      CAC (100+) as compared to CAC 0 (44.7% vs. 3.3%, p<0.05). Increase in CWT was
      associated with increased rates of metabolic syndrome and diabetes mellitus.
      After adjustment for cardiovascular risk factors, the risk of metabolic syndrome
      and DM was 1.7 and 2.3 respectively for each standard deviation (SD) increase in
      CWT. Similarly, the risk for each SD increase in CWT increased with severity of
      CAC as compared to CAC 0 (RR:CAC 1-100:1.2, CAC 101-400:1.5, CAC 400-1000:2.1,
      and CAC 1000+:3.4, respectively). CONCLUSION: Increased CWT is associated with
      the presence and severity of CAC, metabolic syndrome and DM independent of
      conventional cardiovascular risk factors; highlighting the important role of
      comprehensive carotid and coronary atherosclerotic assessment to identify at-risk
      individuals.

PMID- 21196007
TI  - Inlet boundary conditions for blood flow simulations in truncated arterial
      networks.
AB  - In the context of patient-specific cardiovascular applications, hemodynamics
      models (going from 3D to 0D) are often limited to a part of the arterial tree.
      This restriction implies the set up of artificial interfaces with the remaining
      parts of the cardiovascular system. In particular, the inlet boundary condition
      is crucial: it supplies the impulsion to the system and receives the reflected
      backward waves created by the distal network. Some aspects of this boundary
      condition need to be properly defined such as the treatment of backward waves
      (reflected or absorbed) and the value of the imposed hemodynamic wave (total or
      forward component). Most authors prescribe as inlet boundary condition (BC) the
      total measured variable (pressure, velocity or flow rate) in a reflective way. We
      show that with this type of inlet boundary condition, the model does not produce
      physiological waveforms. We suggest instead to prescribe only the forward
      component of the prescribed variable in an absorbing way. In this way, the
      computed reflected waves superpose with the prescribed forward waves to produce
      the total wave at the inlet. In this work, different inlet boundary conditions
      are implemented and compared for a 1D blood flow model. We test our boundary
      conditions on a truncated arterial model presented in the literature as well as
      on a patient-specific lower-limb model of a femoral bypass. We show that with
      this new boundary condition, a much better fitting is observed on the shape and
      intensity of the simulated pressure and velocity waves.

PMID- 21196008
TI  - Determination of resveratrol and piceid in beer matrices by solid-phase
      extraction and liquid chromatography-tandem mass spectrometry.
AB  - Beer is one of the most commonly consumed undistilled alcoholic beverages in many
      countries. In recent studies, the stilbenes resveratrol and piceid have been
      found in some hop varieties which are used in the production of beer. Therefore,
      they could be transferred to beer. The aim of the present work was to validate a
      method to study the potential content of trans- and cis-resveratrol and piceid in
      110 commercial beers from around the world. The resveratrol and piceid contents
      of 110 beers were analyzed by liquid chromatography-tandem mass spectrometry (LC
      MS/MS) after a solid-phase extraction (SPE) using optimized and validated
      procedures for the beer matrix. The beer matrix effect was also studied.
      Stilbenes were found in quantifiable amounts in 92 beers, while concentrations
      below the limit of quantification (LOQ) were found in 18 beers. Resveratrol was
      found in the range of 1.34-77.0MUg/L in 79% of the beers analyzed, and piceid was
      found in the range of 1.80-27.3MUg/L in only 33% of them. The mean of total
      resveratrol in all the beers was 14.7+/-20.5MUg/L. The content of resveratrol has
      been compared with other resveratrol containing foods. A serving of beer contains
      similar amounts of stilbenes as berries, less than chocolate and grape products
      but more than pistachios, peanuts or tomatoes. Overall, beer is one of the
      products with the lowest levels of total resveratrol (MUg/L), and despite its
      high consumption it should not be considered as a representative source of
      resveratrol.

PMID- 21196009
TI  - Quantitative analysis of volatiles from solid matrices of vegetable origin by
      high concentration capacity headspace techniques: determination of furan in
      roasted coffee.
AB  - The study compares standard addition (SA), stable isotope dilution assay (SIDA)
      and multiple headspace extraction (MHE) as methods to quantify furan and 2-methyl
      furan in roasted coffee with HS-SPME-GC-MS, using CAR-PDMS as fibre coating, d(4)
      furan as internal standard and in-fibre internal standardization with n-undecane
      to check the fibre reliability. The results on about 150 samples calculated with
      the three quantitation approaches were all very satisfactory, with coefficient of
      variation (CV) versus the U.S. Food and Drug Administration (FDA) method, taken
      as reference, almost always below the arbitrarily-fixed limit of 15%. Furan was
      detected in the 1-5 ppm range, 2-methyl-furan in the 4-20 ppm range. Moreover,
      experimental exponential slopes (Q) and linearity (r) of both furan and 2-methyl
      furan MHE regression equation on 50 samples were very similar thus making
      possible to use the same average Q value for all samples of the investigated set
      and their quantitation with a single determination. This makes this approach very
      rapid and competitive in-time with SA and SIDA. A non-separative method (HS-SPME
      MS) was also developed in view of possible application on-line monitoring of
      furan and 2-methyl-furan in a pilot-plant with the aim of optimizing the roasting
      process to reduce these compounds to a minimum. Sampling times of 20 and 5 min
      were tested, the latter enabling total analysis time to be reduced to about 9
      min. The results on 105 samples with both SIDA and MHE approaches were again
      highly satisfactory most of the samples giving a CV% versus the conventional
      methods below 20%. In this case too average Q values for both furan and 2-methyl
      furan were used for MHE. The separative method presented very good repeatability
      (RSD% always below 10%) and intermediate precision over three months (RSD% always
      below 15%); performance were similar for the non-separative method, with
      repeatability (RSD%) always below 12% and intermediate precision over three
      months (RSD%) always below 15%. The sensitivity of both separative and non
      separative methods was also very good, LOD and LOQ being in the ppb range for
      both furan and 2-methyl-furan, i.e. well below the amounts present in the roasted
      coffee samples.

PMID- 21196010
TI  - Forensic examination of ink by high-performance thin layer chromatography--the
      United States Secret Service Digital Ink Library.
AB  - Forensic examinations of ink have been performed since the beginning of the 20th
      century. Since the 1960s, the International Ink Library, maintained by the United
      States Secret Service, has supported those analyses. Until 2009, the search and
      identification of inks were essentially performed manually. This paper describes
      the results of a project designed to improve ink samples' analytical and search
      processes. The project focused on the development of improved standardization
      procedures to ensure the best possible reproducibility between analyses run on
      different HPTLC plates. The successful implementation of this new calibration
      method enabled the development of mathematical algorithms and of a software
      package to complement the existing ink library.

PMID- 21196011
TI  - Interfacial water with special electron donor properties: effect of water
      surfactant interaction in confined reversed micellar environments and its
      influence on the coordination chemistry of a copper complex.
AB  - In this work, we have investigated the behavior of the square-planar mixed-ligand
      transition-metal complex N,N,N',N'-tetramethylethylenediamine copper (II)
      acetylacetonate tetraphenylborate, [Cu(acac)(tmen)][B(C(6)H(5))(4)], in anionic
      benzene/sodium 1,4-bis-2-ethylhexylsulfosuccinate (AOT) reverse micelles (RMs) as
      well as in cationic benzene/benzyl-n-hexadecyl dimethylammonium chloride (BHDC)
      RMs with and without water, using absorption spectroscopy. In the absence of
      water, W(0)=[H(2)O]/[surfactant]=0, our results show that the Cu complex
      structures are not the same in both reversed micellar media. In the BHDC RMs, due
      to the Cl(-) counterion present in the system, the Cu complex structure that
      exists at the interface is the neutral [Cu(acac)(tmen)(Cl)]. In contrast, in AOT
      RMs the surfactant sulfonate anion cannot act as a ligand and therefore the
      complex structure is square planar [Cu(acac)(tmen)](+). When water is added to
      both reversed micellar systems, different situations are observed. At low water
      content, the water sequestrated by BHDC RMs is unable to act as electron donor
      because the oxygen nonbonding electron pairs are completely involved in the
      cationic BHDC polar head group solvation through an ion-dipole interaction. On
      the contrary, in AOT RMs the results suggest that since the water molecules
      solvate the sulfonate group through hydrogen bonding interactions, the bulk
      hydrogen bond network is destroyed at the interface and therefore, the nonbonding
      electron pairs are more available to interact with the Cu complex. Thus, the
      electron donor ability of water in AOT RMs is enhanced in comparison with the
      BHDC RMs and bulk water, giving a remarkable electron donor character to the AOT
      reversed micellar interfacial water.

PMID- 21196012
TI  - Morphological control of CaCO3 films with large area: effect of additives and
      self-organization under atmospheric conditions.
AB  - Hierarchically structured CaCO(3) films were synthesized at atmospheric
      conditions (room temperature and 1 atm) without the use of templates or
      amphiphilic molecules in this process. The resulting CaCO(3) film was formed by
      self-organization between Ca(OH)(2) and aqueous CO(2). The building blocks of the
      CaCO(3) film were thought to be CaCO(3) primary nanoparticles that aligned to
      build higher level structures with greater size, called mesocrystals, depending
      on the additives. The soluble additives played a key role in the control of the
      morphology, crystallinity, and polymorphism of the CaCO(3) film, and the effects
      strongly depended on the type of additive and their concentrations. The additives
      used in this study decreased the crystallinity of CaCO(3) (calcite) film in the
      order of glucose > aspartic acid > serine in a manner inversely proportional to
      the concentration of the additives. In addition, Mg(2+), K(+), and Na(+) ion
      additives led to the formation of an aragonite phase, the proportion of which
      increased with the concentration of ions. The threshold concentrations of these
      ions for the formation of the aragonite phase in CaCO(3) film were found to be in
      the order of Na(+) > K(+) > Mg(2+).

PMID- 21196015
TI  - Non-traumatic anterior spinal cord infarction in a novice surfer: a case report.
AB  - We present a case involving a 24-year-old woman who developed anterior spinal
      cord infarction with paraplegia but preserved posterior column sensation shortly
      after her first surfing lesson. The clinical presentation and magnetic resonance
      imaging findings were compatible with anterior cord infarction from T11 to conus
      medullaris. However, a thorough diagnostic workup revealed no predisposing
      factors of ischemia. Like previously reported cases of surfer's myelopathy, our
      patient was inexperienced and lacked trained back muscles, though none of the
      previously related cases were reported to have anterior cord infarction. In this
      case report, we discuss the probable relationship between surfing and ischemic
      myelopathy. Non-traumatic myelopathy in surfing is a relatively new entity
      thought to occur in surfers while paddling their boards in a hyperextended
      position and perform the Valsalva maneuver while attempting to stand up on the
      boards, which may increase intra-spinal pressure. Increased awareness of this
      injury may make it possible to recognize its early symptoms and prevent further
      injury.

PMID- 21196013
TI  - Pretraumatic prolonged elevation of salivary MHPG predicts peritraumatic distress
      and symptoms of post-traumatic stress disorder.
AB  - Post-traumatic stress disorder (PTSD) is associated with elevated catecholamines
      and increased sympathetic arousal. However, it is unknown whether this condition
      is a pre-existing vulnerability factor for PTSD or an acquired result of either
      trauma exposure or the development of PTSD symptoms. We sought to examine if
      salivary 3-methoxy-4-hydroxy-phenylglycol (MHPG) in response to a laboratory
      stressor prior to critical incident exposure predicts the development of PTSD
      symptoms and if early childhood trauma influences this relationship. In a
      prospective cohort study, 349 urban police officers were assessed during academy
      training (baseline) and 243 were reassessed 12 months after the start of active
      duty (follow-up). At baseline, participants observed a video consisting of police
      critical incidents. Salivary MHPG was measured before and immediately after the
      challenge, and after 20min recovery. At follow-up, peritraumatic distress and
      PTSD symptoms were assessed in relationship to the worst critical incident during
      the past year. Participants with childhood trauma showed a trend towards higher
      MHPG increase to the challenge. Higher MHPG levels after 20min recovery were
      associated with both higher levels of peritraumatic distress and PTSD symptoms at
      follow-up. In a path analysis, elevated MHPG levels predicted higher
      peritraumatic distress which in turn predicted higher levels of PTSD symptoms
      while the direct effect of elevated MHPG levels on PTSD symptoms was no longer
      significant. Prolonged elevation of salivary MHPG in response to a laboratory
      stressor marks a predisposition to experience higher levels of peritraumatic
      distress and subsequently more PTSD symptoms following critical incident
      exposure.

PMID- 21196016
TI  - Immuno-localisation of anti-thyroid antibodies in adult human cerebral cortex.
AB  - Expression of thyroid-stimulating hormone receptor (TSH-R) has been demonstrated
      in adipocytes, lymphocytes, bone, kidney, heart, intestine and rat brain. Immuno
      reactive TSH-R has been localised in rat brain and human embryonic cerebral
      cortex but not in adult human brain. We designed a pilot study to determine
      whether anti-thyroid auto-antibodies immuno-localise in normal adult human
      cerebral cortex. Forensic samples from the frontal, motor, sensory, occipital,
      cingulate and parieto-occipito-temporal association cortices were obtained from
      five individuals who had died of trauma. Although there were no head injuries,
      the prior psychiatric history of patients was unknown. The tissues were probed
      with commercial antibodies against both human TSH-R and human thyroglobulin (TG).
      Anti-TSH-R IgG immuno-localised to cell bodies and axons of large neurones in all
      6 regions of all 5 brains. The intensity and percentage of neurones labelled were
      similar in all tissue sections. TSH-R immuno-label was also observed in vascular
      endothelial cells in the cingulate gyrus. Although also found in all 5 brains and
      all six cortical regions, TG localised exclusively in vascular smooth muscle
      cells and not on neurones. Although limited by the small sample size and number
      of brain areas examined, this is the first study describing the presence of
      antigenic targets for anti-TSH-R IgG on human cortical neurons, and anti-TG IgG
      in cerebral vasculature.

PMID- 21196017
TI  - [Improving the quality of randomized trials reports: a collaboration between
      authors, reviewers and editors].

PMID- 21196018
TI  - [Association between herpetic burden and chronic ischemic heart disease: matched
      case-control study].
AB  - BACKGROUND AND OBJECTIVES: Previous studies showed a plausible association
      between herpetic burden and ischemic heart disease. Our aim is to test this
      hypothesis in an spanish seroepidemiological context. PATIENTS AND METHODS: Sex
      and age matched case-control study (1:1) including patients with chronic ischemic
      heart disease and healthy controls. Herpetic burden was defined as the aggregate
      number of antibody seropositivities (IgG) for Epstein Barr Virus,
      cytomegalovirus, varicella zoster virus, Herpes simplex type 1 and type 2.
      RESULTS: We found that 90.7% of cases and 70,7% of controles (P=.002), were
      seropositive to 4 or more herpesvirus (high herpetic burden). Within control
      group, hypercholesterolemic subjects had a higher proportion of high burden
      (88,5% vs. 61,2%, P=.02). High herpetic burden was associated with ischemic heart
      disease, even after adjusting for diabetes, smoking, hypertension and literacy
      level, (OR: 4,5 [1,23-16,53]), but not when hypercholesterolemia was included in
      the model (OR 2,2 [0,45-10,62]). CONCLUSION: The hypothesized relationship is
      independent from most but not all classical cardiovascular risk factors.

PMID- 21196019
TI  - [Four-month history of weakness of lower limbs in a 50-years-old male].

PMID- 21196020
TI  - [Is the endothelial circulating microparticles analysis enough to assess the
      inflammatory status related to preeclampsia?].

PMID- 21196021
TI  - Antiviral activity of Alpinia katsumadai extracts against rotaviruses.
AB  - In vitro anti-rotavirus activity of Alpinia katsumadai (AK) extracts were
      evaluated against bovine G8P[7] and porcine G5P[7] rotaviruses in two different
      assay strategies, a mixed treatment assay and a post treatment assay. In the
      mixed treatment assay, six AK extracts [AK-1 (EtOH extract), AK-3 (H(2)O layer),
      AK-5 (40% methanol fraction), and AK-9-11 (H(2)O extract, polysaccharide
      fraction, supernatant fraction)] exhibited inhibitory activities against G5P[7]
      rotavirus with the EC(50) values ranging from 0.7+/-0.4 to 33.7+/-6.5 MUg/mL.
      Extracts AK-1, AK-3, and AK-5 inhibited rotavirus infection against G8P[7]
      rotavirus, the with EC(50) values of 8.4+/-2.2 MUg/mL, 6.5+/-0.8 MUg/mL and 8.4+/
      5.0 MUg/mL, respectively. By hemagglutination inhibition (HI) assay, six AK
      extracts completely inhibited viral adsorption onto human RBCs in both strains of
      rotaviruses at less than 11 MUg/mL. However, in the post treatment assay, there
      was no anti activity shown against both strains of rotaviruses. As a result, six
      AK extracts were attributed mainly to having a strong interaction with
      hemagglutinin protein on the outer surface of rotavirus, resulting to blockage of
      viral adsorption.

PMID- 21196022
TI  - Antiviral activity of rChIFN-alpha against vesicular stomatitis virus and
      Newcastle disease virus: a novel recombinant chicken interferon-alpha showed high
      antiviral activity.
AB  - The sequences of 27 chicken interferon-alpha (ChIFN-alpha) genes were obtained
      from GenBank. The gene sequences were compared and homology between them was
      determined by using a bio-software. On the basis of these results, a new rChIFN
      alpha peptide sequence with 194 amino acids was assembled. Thereafter, on the
      basis of the new amino acid sequences and by using the most frequently occurring
      codes of Pichia pastoris, and a 582 bp gene sequence was formed. In order to
      amplify this non-templated gene, 16 primers were designed, and their gene
      sequences were synthesized, and amplified. This amplified gene sequence was
      cloned into the expression vector pPICZalpha-A to construct a recombination
      plasmid named pPICZ-rChIFN-alpha. Then, the recombination plasmid was induced to
      express the rChIFN-alpha protein. The results demonstrated that the recombinant
      plasmid pPICZ-rChIFN-alpha was successfully expressed in P. pastoris.
      Furthermore, rChIFN-alpha had a considerable antiviral activity against both
      Newcastle disease virus (NDV) and vesicular stomatitis virus (VSV). Therefore,
      this method of gene engineering could give direction to research on the key amino
      acids in the interferon or analogous proteins and enable the construction of
      proteins with high antiviral activity, which can be used both for research and
      industrial purposes.

PMID- 21196023
TI  - Accelerated biodegradation of pyrene and benzo[a]pyrene in the Phragmites
      australis rhizosphere by bacteria-root exudate interactions.
AB  - We investigated the biodegradation of pyrene and benzo[a]pyrene in Phragmites
      australis rhizosphere sediment. We collected P. australis plants, rhizosphere
      sediments, and unvegetated sediments from natural aquatic sites and conducted
      degradation experiments using sediments spiked with pyrene or benzo[a]pyrene.
      Accelerated removal of pyrene and benzo[a]pyrene was observed in P. australis
      rhizosphere sediments with plants, whereas both compounds persisted in
      unvegetated sediments without plants and in autoclaved rhizosphere sediments with
      sterilized plants, suggesting that the accelerated removal resulted largely from
      biodegradation by rhizosphere bacteria. Initial densities of pyrene-utilizing
      bacteria were substantially higher in the rhizosphere than in unvegetated
      sediments, but benzo[a]pyrene-utilizing bacteria were not detected in rhizosphere
      sediments. Mycobacterium gilvum strains isolated from rhizosphere sediments
      utilized pyrene aerobically as a sole carbon source and were able to degrade
      benzo[a]pyrene when induced with pyrene. Phragmites australis root exudates
      containing phenolic compounds supported growth as a carbon source for the one
      Mycobacterium strain tested, and induced benzo[a]pyrene-degrading activity of the
      strain. The stimulatory effect on benzo[a]pyrene biodegradation and the amounts
      of phenolic compounds in root exudates increased when P. australis was exposed to
      pyrene. Our results show that Mycobacterium-root exudate interactions can
      accelerate biodegradation of pyrene and benzo[a]pyrene in P. australis
      rhizosphere sediments.

PMID- 21196024
TI  - Concentration of DL-PCBs in fish from market of Parma city (north Italy):
      estimated human intake.
AB  - The concentrations of 12 congeners of non-ortho and mono-ortho dioxin-like
      polychlorinated biphenyls (SigmaDL-PCB) were measured in 30 fish samples from
      Parma markets by GC/MS technique. The samples were randomly purchased, choosing
      the species commonly found in supermarkets. The concentration of DL-PCBs
      estimated remained under the fixed Italian limit of 4 pg g(-1)ww WHO-TEQ (World
      Health Organization-Toxic Equivalent) in the major part of the samples, so the
      situation seems to be not at a level sufficient to pose a risk to human health of
      the Parma population. The medium daily intake for DL-PCBs for Italian consumers
      (Parma) was also estimated. This value generally resulted minor than 2 pg g(-1)
      ww WHO-TEQ kg(-1) body weight, exceeding only in four cases: eel, smooth hound,
      starry smooth hound and tuna.

PMID- 21196025
TI  - Associations of fat mass and lean mass with bone mineral density differ by levels
      of persistent organic pollutants: National Health and Nutrition Examination
      Survey 1999-2004.
AB  - Persistent organic pollutants (POPs), xenobiotics that accumulate in fat tissue,
      may impair bone metabolism. We studied (1) the association of bone mineral
      density (BMD) with POPs and (2) whether associations of fat mass (FM) or lean
      mass (LM), two components of body composition, with BMD differed depending on
      levels of POPs. Participants aged >= 20 in the National Health and Nutrition
      Examination Survey 1999-2004 were included (n=2769). Eight POPs with detection
      rate >= 80% and three skeletal subregions (left arm, pelvis, and right leg) were
      selected. All analyses were stratified by gender and age (cutpoint 50 years or
      more). POPs at background concentrations were mostly unassociated with BMD.
      However, the associations of FM and LM with BMD depended on POPs concentrations,
      in particular with BMD of the left arm (usually not weight-bearing) in
      postmenopausal women. When POPs concentrations were low, FM showed inverse
      associations with BMD while LM showed positive associations. However, when POPs
      levels were high, FM showed positive associations with BMD while the positive
      associations between LM and BMD weakened. POPs may biologically modify the
      associations of FM and LM with BMD, especially among postmenopausal women,
      possibly explaining inconsistent associations between FM and BMD in previous
      epidemiological studies.

PMID- 21196026
TI  - Quantum dots brighten biological imaging.
AB  - Quantum dots (QDs) are novel photostable semiconductor nanocrystals possessing
      wide excitation spectra and narrow, symmetrical emission spectra and can be
      conjugated to a wide range of biological targets, including proteins, antibodies
      and nucleic acid probes. These characteristics have provoked considerable
      interest in their use for bioimaging. Much investigation has been performed into
      their use for multiplex immunohistochemistry and in situ hybridisation which,
      when combined with multispectral imaging, has enabled quantitation and
      colocalisation of gene expression in clinical tissue. Many advances have recently
      been made using QDs for live cell and in vivo imaging, in which QD-labelled
      molecules can be tracked and visualised in 3-D. This review aims to outline the
      beneficial properties presented by QDs along with important advances in their
      biological application.

PMID- 21196027
TI  - Quantitative assessment of the probability of bluetongue virus transmission by
      bovine semen and effectiveness of preventive measures.
AB  - Given that bluetongue (BT) may potentially be transmitted by semen, that the
      disease has significantly expanded in recent years, and that millions of doses of
      cattle semen are annually traded throughout the world, the transmission of
      bluetongue virus (BTV) by semen could have severe consequences in the cattle
      industry. The hypothesis that infected bulls could excrete BTV in their semen led
      to restrictions on international trade of ruminant semen and the establishment of
      measures to prevent BTV transmission by semen. However, neither the risk of BTV
      transmission by semen nor the effectiveness of these measures was estimated
      quantitatively. The objective of the study was to assess, in case of introduction
      of BTV into a bovine semen collection centre (SCC), both the risk of BTV
      transmission by bovine semen and the risk reduction achieved by some of the
      preventive measures, by means of a stochastic risk assessment model. The model
      was applied to different scenarios, depending on for example the type of
      diagnostic test and the interval between the controls (testing) of donor bulls,
      or the rate of BTV spread within the SCC. Enzyme-linked immunosorbant assay
      (ELISA) controls of donor bulls every 60 days seemed to be an ineffective method
      for reducing the risk of BTV transmission in contrast to polymerase chain
      reaction (PCR) tests every 28 days. An increase in the rate of spread within the
      SCC resulted in a reduced risk of BTV transmission by semen. The storage of semen
      for 30 days prior to dispatch seemed to be an efficient way of reducing the risk
      of transmission by semen. The sensitivity analysis identified the probability of
      BTV shedding in semen as a crucial parameter in the probability of BTV
      transmission by semen. However, there is a great degree of uncertainty associated
      with this parameter, with significant differences depending on the BTV serotype.

PMID- 21196028
TI  - Litter size at birth in purebred dogs--a retrospective study of 224 breeds.
AB  - Despite the long history of purebred dogs and the large number of existing
      breeds, few studies of canine litter size based upon a large number of breeds
      exist. Previous studies are either old or include only one or a few selected
      breeds. The aim of this large-scale retrospective study was to estimate the mean
      litter size in a large population of purebred dogs and to describe some factors
      that might influence the litter size. A total of 10,810 litters of 224 breeds
      registered in the Norwegian Kennel Club from 2006 to 2007 were included in the
      study. The overall mean litter size at birth was 5.4 (+/- 0.025). A generalized
      linear mixed model with a random intercept for breed revealed that the litter
      size was significantly influenced by the size of the breed, the method of mating
      and the age of the bitch. A significant interaction between breed size and age
      was detected, in that the expected number of puppies born decreased more for
      older bitches of large breeds. Mean litter size increased with breed size, from
      3.5 (+/- 0.04) puppies in miniature breeds to 7.1 (+/- 0.13) puppies in giant
      breeds. No effect on litter size was found for the season of birth or the parity
      of the bitch. The large number of breeds and the detail of the registered
      information on the litters in this study are unique. In conclusion, the size of
      the breed, the age of the bitch and the method of mating were found to influence
      litter size in purebred dogs when controlling for breed, with the size of the
      breed as the strongest determinant.

PMID- 21196029
TI  - Effect of leptin supplementation during in vitro oocyte maturation and embryo
      culture on bovine embryo development and gene expression patterns.
AB  - Leptin is a metabolic hormone related to body condition and nutritional status
      that influences fertility in assisted reproductive technologies modulating oocyte
      and embryo quality. The aim of the present study was to establish the effect of
      various leptin concentrations (0, 10, 100 ng/mL) during in vitro oocyte
      maturation (IVM) and in vitro embryo culture (IVC) on bovine embryo development
      and quality in terms of gene expression. The relative mRNA abundance of the genes
      encoding solute carrier family 2 (facilitated glucose transporter) member 1
      (SLC2A1), Bcl-2-associated X protein (BAX), placenta-specific 8 (PLAC8), aldo
      keto reductase family 1 member B1 (AKR1B1) and leptin receptor (LEPR) were
      determined on Day 7 blastocysts by qRT-PCR. Cleavage rate (P < 0.005) and
      blastocyst yield (P = 0.05) was significantly lower when cumulus-oocyte complexes
      (COCs) were matured with 100 ng/mL leptin compared to 0 or 10 ng/mL leptin. No
      significant effect of different concentrations of leptin added during IVC on
      blastocyst yield was observed. The presence of 100 ng/mL leptin in both IVM and
      IVC further decreased cleavage rate (P < 0.005) and blastocyst yield compared to
      the control group without leptin (P = 0.05) and those supplemented with 10 ng/mL
      leptin or FCS (P < 0.005). There was no evidence of any leptin-induced difference
      in the relative transcript abundance of SLC2A1, BAX and PLAC8 genes in Day 7
      blastocysts. Expression of AKR1B1 was significantly lower in blastocysts from
      COCs matured with 100 ng/mL leptin compared to those matured with 0 or 10 ng/mL
      leptin (P < 0.005). LEPR expression was up regulated when leptin concentration
      was increased from 0 ng/mL during IVM to 10 ng/mL during IVC, but it was down
      regulated in the opposite situation (P < 0.005). In conclusion, high leptin
      concentrations possibly related to obesity seem to be more detrimental rather
      than the absence of this hormone for preimplantation embryo survival; this effect
      is independent of LEPR gene expression and it does not influence expression of
      SLC2A1, BAX and PLAC8 genes in Day 7 blastocysts.

PMID- 21196030
TI  - Evidence of genetic and maternal effects on secondary sex ratio in cattle.
AB  - There is a paucity of estimates of genetic variation for secondary sex ratio
      (i.e., sex ratio at birth) in dairy cattle. The objective of this study was to
      estimate the direct and maternal genetic variance as well as maternal permanent
      environmental variance for offspring sex in dairy herds. The data consisted of
      77,508 births from 61,963 dams and 2,859 sires in 1,369 Irish dairy herds across
      the years 2003 to 2008, inclusive. Mixed models were used to estimate all
      parameters. Significant genetic variation in sex ratio existed, with a
      heritability for secondary sex ratio estimated at 0.02; the genetic standard
      deviation was 0.07 percentage units. No maternal genetic effects on secondary sex
      ratio were identified but the proportion of phenotypic variance in secondary sex
      ratio attributable to maternal permanent environmental effects was similar to
      that attributable to the additive genetic variance (i.e., 0.02). These results,
      therefore, suggest that the paternal (genetic) influence on secondary sex ratio
      is just as large as the maternal (non-genetic) influence, both of which are
      biologically substantial. The results from this study will be useful in
      generating a sample population of divergent animals for inclusion in a controlled
      experiment to elucidate the physiological mechanism underpinning differences in
      secondary sex ratio.

PMID- 21196031
TI  - Ultrasonographic evaluation of endometrial thickness near timed AI as a predictor
      of fertility in high-producing dairy cows.
AB  - The objectives were to evaluate changes in endometrial thickness (ET) near the
      time of a synchronized ovulation and to assess the relationship of ET and
      fertility in lactating Holstein cows, with or without estrogen supplementation
      near timed ovulation. In Experiment 1, eight cows were examined with transrectal
      ultrasonography, once daily for 5 d, starting concurrent with PGF(2alpha) (PGF)
      treatment during an Ovsynch protocol (GnRH - 7d - PGF - 72h - GnRH). The ET
      increased rapidly after PGF (from ~7 to ~9.5 mm), remained > 9 mm for the next 2
      d, then decreased to ~8 and 7.4 mm, 1 and 2 d, respectively, after the second
      GnRH. In Experiment 2,642 cows (total of 758 breedings) were subjected to an
      Ovsynch protocol (GnRH - 7d - PGF - 56h - GnRH - 16h - timed AI); cows received
      either no further treatment (Ovsynch) or 1 mg of estradiol-17beta im 8 h before
      the second GnRH (Ovsynch + E2). For both uterine horns, ET was measured (~2 cm
      from the internal uterine body bifurcation) before E2 treatment (48 h after PGF).
      In cows with ET <= 8 mm vs > 8 mm, rates of ovulation were 86.0% (n = 136) vs
      98.1% (n = 472; P < 0.01), respectively, and percentage pregnant per AI (P/AI)
      were 26.7% (n = 146) vs 42.7% (n = 524; P < 0.01). Treatment with E2 increased
      P/AI in cows with lower ET (Ovsynch + E2 = 37.0% vs Ovsynch = 23.3%; P = 0.07),
      but did not significantly improve P/AI in cows with ET > 8 mm (Ovsynch + E2 =
      43.4% vs Ovsynch = 42.1%). In conclusion, a single ultrasonographic evaluation of
      ET in Holstein cows 48 h after PGF treatment in an Ovsynch program was a good
      predictor of ovulation failure and pregnancy success. Perhaps poor fertility in
      cows with reduced ET was low peripheral E2 concentrations near AI, poor P4
      priming, or luteolysis failure during timed AI procedures.

PMID- 21196032
TI  - Distribution of estrogen receptor alpha and progesterone receptor, and leukocyte
      infiltration in the cervix of cyclic bitches and those with pyometra.
AB  - The objectives were to localize estrogen receptor alpha (ERalpha) and
      progesterone receptor (PR), and enumerate leukocyte infiltration in cervical
      tissue of normal bitches during various stages of the estrous cycle (n = 35), as
      well as in those developing open (n = 22) or closed-cervix pyometra (n = 19).
      Each pyometra group was subdivided into anestrus and diestrus. Cervical tissues
      were collected after ovariohysterectomy. Receptor expressions were determined by
      immunohistochemistry and leukocyte infiltration was evaluated in histological
      sections stained with haematoxylin-eosin. The assessment was performed in two
      parts of cervical sections: the uterine part in four tissue layers (surface
      epithelium (SE), lamina propria (LP), glandular epithelium (GE), and tunica
      muscularis (M)), and the vaginal part in three layers (SE, LP and M). An
      immunohistochemical total score consisted of the addition of both the intensity
      and proportional scores. The ERalpha and PR scores differed between groups (P <
      0.05) and between layers (P < 0.05), but were not significantly different between
      uterine and vaginal parts. The ERalpha score was lowest in the open-cervix
      pyometra bitches at anestrus and in closed-cervix pyometra bitches at diestrus.
      For all types of immune cells, there were no significant differences among stages
      of the estrous cycle in normal bitches, whereas neutrophils were lower in both
      sub-groups of closed-cervix versus open-cervix pyometra (P < 0.05). In
      conclusion, distributions of ERalpha and PR were similar along the longitudinal
      axis of the canine cervix. We inferred that cervical dilation in normal bitches
      and bitches with uterine pathology was likely controlled by different mechanisms.
      Receptor expressions were influenced by stage of the estrous cycle in normal
      bitches, whereas neutrophil infiltration in cervical tissue appeared to be
      involved in cervical dilation in bitches with pyometra, regardless of estrous
      stages.

PMID- 21196033
TI  - Two-dimensional polyacrylamide gel electrophoresis of membrane proteins from flow
      cytometrically sorted ram sperm.
AB  - Membrane proteins orchestrate key events required for participation of sperm in
      fertilisation. These proteins may be removed or altered due to the mechanical and
      dilution stressors associated with sex-sorting of sperm. Ram sperm were incubated
      with Hoechst 33342 and flow-sorted. Sex-selected (viable, orientated) and waste
      (separated into non-viable or non-orientated) sperm populations were collected,
      or sperm were not sorted. Sperm membrane proteins were extracted and
      characterised by one- and two-dimensional PAGE. Densiometric analysis of protein
      bands separated by one-dimensional PAGE showed proteins of 30 and 28 kDa as
      doublet bands on non-sorted sperm, and single bands on sex-sorted sperm, and the
      proportion of a 14 kDa protein was 3-fold higher in non-sorted compared to sorted
      sperm. Proteins in the 14 kDa band were identified by mass spectroscopy as a
      bovine Fibronectin type-2 protein (Fn-2), cytochrome oxidase 5a (Cox5a) and a
      sperm membrane associated protein (SLLP1). The abundance of these proteins in the
      two-dimensional gels was lowest in the sorted sperm population identified as
      viable during sorting (orientated and non-orientated sperm) and highest in the
      non-viable sperm population (P < 0.001). We concluded that the membrane protein
      profile was different for sex-sorted compared with non-sorted sperm, due to the
      selection of plasma membrane-intact cells in the flow-sorted population. This
      provided further evidence that sex-sorting selected a homogenous population of
      sperm with superior function to non-sorted sperm. Furthermore, this was
      apparently the first time sperm membrane acrosome associated protein was reported
      in ram sperm, and it was demonstrated that seminal plasma proteins remained on
      the sperm membrane after sex-sorting.

PMID- 21196034
TI  - Ovarian parameters and fertility of dairy cows selected for one QTL located on
      BTA3.
AB  - Recently, one Quantitative Trait Locus (QTL) of female fertility located on Bos
      Taurus chromosome 3 (BTA3), QTL-F-Fert-BTA3, has been identified in Holstein
      breed. It is implied in the success rate after the first AI (AI1) in cow. The
      failure of pregnancy can be due to several factors involved in the different
      steps of the reproductive process. The aim of our study was to finely phenotype
      heifers and primiparous cows selected for their haplotype at the QTL-F-Fert-BTA3.
      We specifically studied the ovarian follicular dynamic and several fertility
      parameters. Females carrying the favourable haplotype "fertil+" or unfavourable
      haplotype "fertil-" were monitored by transrectal ultrasonography during their
      cycle before the first AI (AI1). Follicular dynamic was similar between the two
      groups. However, the length of the estrus cycle was shorter in heifers than in
      primiparous cows and two-wave cycles were shorter than three-wave cycles,
      regardless of the age and the haplotype. The concentration of plasma anti
      Mullerian hormone was correlated with the number of small antral follicles. It
      was higher in heifers than in primiparous cows, independently of their haplotype.
      The success rate at the AI1 was significantly higher in "fertil+" than in "fertil
      " primiparous cows, 35 d after the AI1 (70% vs 39%). In both haplotypes,
      pregnancy failure occurred mainly before 21 d after AI1. The commencement of
      luteal activity after calving was significantly earlier in "fertil+" than in
      "fertil-" primiparous cows. Calving-AI1 and calving-calving intervals were
      similar between "fertil+" and "fertil-" primiparous cows. Taken together,
      "fertil+" and "fertil-" primiparous cows present a difference in the success rate
      after AI1 that is not explained by variations of ovarian dynamics.

PMID- 21196036
TI  - Purification, sequence characterization and effect of goat oviduct-specific
      glycoprotein on in vitro embryo development.
AB  - Oviduct-specific glycoprotein (oviductin) plays an important role during
      fertilization and early embryonic development. The oviductin cDNA was
      successfully cloned and sequenced in goat, which possessed an open reading frame
      of 1620 nucleotides representing 539 amino acids. Predicted amino acid sequence
      showed very high identity with sheep (97%) followed by cow (94%), porcine (77%),
      hamster (69%), human (66%), rabbit (65%), mouse (64%) and baboon (62%). The
      bioinformatics analysis of the sequences revealed the presence of a signal
      sequence of 21 amino acids, one potential N-linked glycosylation site at position
      402, 21 potential O-linked glycosylation sites and 36 potential phosphorylation
      sites. The native oviductin was purified from the oviductal tissue, which showed
      three distinct bands on SDS-PAGE and western blot (MW ~60-95 kDa). The predicted
      molecular weight of goat oviductin was 57.5 kDa, calculated from the amino acid
      sequences. The observed higher molecular weight has been attributed to the
      presence of large number of potential O-linked glycosylation sites. The lower
      concentration (10 MUg/mL) of oviductin increased the cleavage rate, morula and
      blastocyst yield significantly (P < 0.05) as compared to higher concentration
      (100 MUg/mL). Goat oviductin retarded the activity of pronase (0.1%) on zona
      solubility of oocytes significantly (P < 0.01).

PMID- 21196035
TI  - The effects of estradiol and catecholestrogens on uterine glycogen metabolism in
      mink (Neovison vison).
AB  - Glycogen is a uterine histotroph nutrient synthesized by endometrial glands in
      response to estradiol. The effects of estradiol may be mediated, in part, through
      the catecholestrogens, 2-hydroxycatecholestradiol (2-OHE2) and 4
      hydroxycatecholestradiol (4-OHE2), produced by hydroxylation of estradiol within
      the endometrium. Using ovariectomized mink, our objectives were to determine the
      effects of estradiol, 4-OHE2, and 2-OHE2 on uterine: 1) glycogen concentrations
      and tissue localization; 2) gene expression levels for glycogen synthase,
      glycogen phosphorylase, and glycogen synthase kinase-3B; and 3) protein
      expression levels for glycogen synthase kinase-3B (total) and phospho-glycogen
      synthase kinase-3B (inactive). Whole uterine glycogen concentrations (mean +/-
      SEM, mg/g dry wt) were increased by estradiol (43.79 +/- 5.35), 4-OHE2 (48.64 +/-
      4.02), and 2-OHE2 (41.36 +/- 3.23) compared to controls (4.58 +/- 1.16; P <=
      0.05). Percent glycogen content of the glandular epithelia was three-fold greater
      than the luminal epithelia in response to estradiol and 4-OHE2 (P <= 0.05).
      Expression of glycogen synthase mRNA, the rate limiting enzyme in glycogen
      synthesis, was increased by 4-OHE2 and 2-OHE2 (P <= 0.05), but interestingly, was
      unaffected by estradiol. Expression of glycogen phosphorylase and glycogen
      synthase kinase-3B mRNAs were reduced by estradiol, 2-OHE2, and 4-OHE2 (P <=
      0.05). Uterine phospho-glycogen synthase kinase-3B protein was barely detectable
      in control mink, whereas all three steroids increased phosphorylation and
      inactivation of the enzyme (P <= 0.05). We concluded that the effects of
      estradiol on uterine glycogen metabolism were mediated in part through
      catecholestrogens; perhaps the combined actions of these hormones are required
      for optimal uterine glycogen synthesis in mink.

PMID- 21196037
TI  - Clinical efficacy of a GnRH-agonist implant containing 4.7 mg deslorelin,
      Suprelorin, regarding suppression of reproductive function in tomcats.
      Sandra.Pesch@vetmed.uni-giessen.de.
AB  - The aim of the present study was to test for the efficacy of a slow release GnRH
      agonist implant (4.7 mg deslorelin, Suprelorin) in the male cat. Ten toms were
      implanted sc in the neck. Changes in testosterone (T) secretion, testicular size,
      body weight and behaviour (mounting, mating, urine marking) were monitored. T
      concentrations were significantly decreased (P < 0.0001) to basal levels (< 0.1
      ng/mL) in 5 of 10 cats after 4 weeks and in all but one tom after 11 weeks (T <
      0.1 ng/mL). In this respective tom only partial downregulation with T-values from
      0.2 to 0.1 ng/mL was achieved until week 27. In weeks 28 and 32, T concentrations
      were below 0.1 ng/mL. Compared to pretreatment values, testicular volume was
      significantly decreased by about 60% in week 12 and about 73% after 36 weeks (P <
      0.001). Penile spines disappeared 9.4 +/- 1.0 weeks after treatment. Food intake
      was significantly increased during treatment period (P < 0.001). In all tomcats
      libido, mating behaviour and urine marking were significantly reduced (P <
      0.0001) after an initial stimulation. In one tom, mating an oestrous queen on day
      20 after implant administration resulted in pregnancy. Mating of another tom that
      had T-values between 0.1 and < 0.1 ng/mL since day 24 in week 8 revealed the
      presence of spermatozoa; however, this mating did not result in pregnancy.
      Subcutaneous implant administration was well tolerated by all tomcats without
      sedation or anaesthesia and no treatment related negative effects were observed.
      These results demonstrate the clinical efficacy of the 4.7 mg deslorelin implants
      (Suprelorin) in the tom inducing all castration related effects.

PMID- 21196038
TI  - The relationship between postpartum vaginal discharge symptoms and progesterone
      profile characteristics in lactating dairy cows in Denmark.
AB  - In this paper, the effect of clinical symptoms of uterine inflammation on
      progesterone profile characteristics was quantified in dairy cows. A continuous
      scale based on visual observation of vaginal discharge (the previously developed
      D-index) was used to describe the clinical symptoms. Progesterone profiles in
      milk were used to describe the ovarian cycles, and to determine the
      distinguishing features of these profiles, a multivariate statistical procedure
      (principal component analysis) was performed. Significant negative effects of the
      D-index were seen during the first and second postpartum ovarian cycles. The D
      index had a significant effect on the shape of progesterone profiles and the
      length of the ovarian cycles but it only accounted for a small proportion of the
      variation in these ovarian cycle features. The D-index was not a significant risk
      factor for the length of postpartum anovulatory period in the present study.

PMID- 21196039
TI  - Markers of stemness in equine mesenchymal stem cells: a plea for uniformity.
AB  - Mesenchymal stromal cells (MSC) are a very promising subpopulation of adult stem
      cells for cell-based regenerative therapies in veterinary medicine. Despite major
      progress in the knowledge on adult stem cells during recent years, a proper
      identification of MSC remains a challenge. In human medicine, the Mesenchymal and
      Tissue Stem Cell Committee of the International Society for Cellular Therapy
      (ISCT) recently proposed three criteria to define MSC. Firstly, cells must be
      plastic-adherent when maintained under standard culture conditions. Secondly, MSC
      must express CD73, CD90 and CD105, and lack expression of CD34, CD45, CD14 or
      CD11b, CD79alpha or CD19 and MHC class II antigens. Thirdly, MSC must be able to
      differentiate into osteoblasts, adipocytes and chondroblasts in vitro. Successful
      isolation and differentiation of equine MSC from different sources such as bone
      marrow, fat tissue, umbilical cord blood, Wharton's Jelly or peripheral blood has
      been widely reported. However, their unequivocal immunophenotyping is hampered by
      the lack of a single specific marker and the limited availability of monoclonal
      anti-horse antibodies, which are two major factors complicating successful
      research on equine MSC. Detection of gene expression on mRNA level is hereby a
      valuable alternative, although the need still exists to test several antibody
      clones in search for cross-reactivity. To date, commercial antibodies recognizing
      equine epitopes are only available for CD13, CD44 and MHC-II. Moreover, as the
      expression of certain adult stem cell markers may differ between species, it is
      mandatory to define a set of CD markers which can be uniformly applied for the
      identification of equine MSC.

PMID- 21196040
TI  - Possible involvement of Class III phosphatidylinositol-3-kinase in meiotic
      progression of porcine oocytes beyond germinal vesicle stage.
AB  - Phosphatidylinositol-3-kinases (PI3Ks) play pivotal roles in meiotic progression
      of oocytes from metaphase I to metaphase II stage. Using a Class III-specific
      inhibitor of PI3K, 3-methyladenine (3MA), this study shows that Class III PI3K
      may be essential for meiotic progression of porcine oocytes beyond germinal
      vesicle (GV) stage. Treatment of immature porcine oocytes with 3MA for 22-42 h
      arrested them at the GV stage, irrespective of the presence or absence of cumulus
      cells. Furthermore, a significantly high proportion (60.9 +/- 13.8%) of 3MA
      treated oocytes acquired a nucleolus completely surrounded by a rim of highly
      condensed chromatin (GV-II stage). The GV-arresting effect of 3MA was, however,
      completely reversible upon their further culture in the absence of 3MA for 22 h.
      When cumulus-oophorus-complexes (COCs), arrested at the GV stage for 22 h by 3MA,
      were further cultured for 22 h in the absence of 3MA, 96.1 +/- 1.5% of oocytes
      reached the MII stage at 42 h of IVM and did not differ from non-treated control
      oocytes with respect to their ability to fertilize, cleave and form blastocyst (P
      > 0.05) upon in vitro fertilization (IVF) or parthenogenetic activation (PA).
      These data suggest that 3MA efficiently blocks and synchronizes the meiotic
      progression of porcine oocytes at the GV stage without affecting their ooplasmic
      maturation in terms of post-fertilization/activation in vitro embryonic
      development. Our data also provide indirect evidence for the likely participation
      of Class III PI3K in meiotic maturation of porcine oocyte beyond the GV stage.

PMID- 21196041
TI  - A breed-matched case-control study of potential risk-factors for canine pyometra.
AB  - The objective was to evaluate plausible risk-factors for pyometra, a common
      disease affecting almost 25% of all (unspayed) female dogs before 10 years of
      age. Because of the strong breed-predilection, an age- and breed-matched case
      control study was undertaken on 87 pairs (pyometra-cases and healthy controls)
      from five breeds (Rottweiler (n = 13), Collie (n = 8), Golden retriever (n = 24),
      Labrador retriever (n = 16) and German shepherd dog (n = 26)). The mean age was
      7.9 y (range 0.8-13.8 y). Variables analyzed included pseudopregnancy, age at
      first oestrus, length of and regularity of the interoestrus interval, hormone
      treatments, nulliparity, number of parities, age at first whelping, previous
      urinary tract infections and mammary tumours. Data were modelled multivariably
      using matched-pair conditional logistic regression. Analysing interactions with
      breed, previous pregnancy was statistically associated with pyometra. When
      amalgamated, in three breeds previous pregnancy was protective (Rottweiler,
      Collie, Labrador retriever) and in one breed statistically intermediate (German
      shepherd dog) when compared to the baseline (Golden retriever). Previous
      pregnancy was a statistically significant factor that had a protective effect
      against pyometra in some breeds but not in the Golden retriever breed. These
      findings indicate that protective- and risk-factors may vary between different
      breeds. The obvious problem with low power and limited possibility for
      extrapolation, using few dogs in few breeds, is acknowledged. However, it is
      suggested that failure to control for the confounding effect of breed, especially
      in epidemiological studies on dog diseases, may lead to potentially erroneous
      conclusions.

PMID- 21196042
TI  - Quality and fertility of cooled-shipped stallion semen at the time of
      insemination.
AB  - Stallion semen processing is far from standardized and differs substantially
      between AI centers. Suboptimal pregnancy rates in equine AI may primarily result
      from breeding with low quality semen not adequately processed for shipment. It
      was the aim of the study to evaluate quality and fertility of cooled-shipped
      equine semen provided for breeding of client mares by commercial semen collection
      centers in Europe. Cooled shipped semen (n = 201 doses) from 67 stallions and 36
      different EU-approved semen collection centers was evaluated. At arrival, semen
      temperature was 9.8 +/- 0.2  degrees C, mean sperm concentration of AI doses was
      68 +/- 3 x 10(6)/ml), mean total sperm count was 1.0 +/- 0.1 x 10(9), total
      motility averaged 83 +/- 1% and morphological defects 45 +/- 2%. A total of 86
      mares were inseminated, overall per season-pregnancy rate in these mares was 67%.
      Sperm concentration significantly influenced semen motility and morphology at
      arrival of the shipped semen. Significant effects of month of the year on volume,
      sperm concentration and total sperm count of the insemination dose were found.
      The collection center significantly influenced all semen parameters evaluated.
      Semen doses used to inseminate mares that became pregnant had significantly
      higher total and progressive motility of spermatozoa and a significantly lower
      percentage of morphological semen defects than insemination doses used for mares
      failing to get pregnant. Results demonstrate that insemination with semen of
      better quality provides a higher chance to achieve pregnancy. Besides the use of
      stallions with good semen quality, appropriate semen processing is an important
      factor for satisfying results in artificial insemination with cooled-shipped
      horse semen.

PMID- 21196043
TI  - Resurrection of an alpha-1,3-galactosyltransferase gene-targeted miniature pig by
      recloning using postmortem ear skin fibroblasts.
AB  - Animals with a targeted disruption of genes can be produced by somatic cell
      nuclear transfer (SCNT). However, difficulties in clonal selection of somatic
      cells with a targeted mutation often result in heterogeneous nuclear donor cells,
      including gene-targeted and non-targeted cells, and impose a risk of producing
      undesired wildtype cloned animals after SCNT. In addition, the efficiency of
      cloning by SCNT has remained extremely low. Most cloned embryos die in utero, and
      the few that develop to term show a high incidence of postnatal death and
      abnormalities. In the present study, resurrection of an alpha-1,3
      galactosyltransferase (alphaGT) gene-targeted miniature pig by recloning using
      postmortem ear skin fibroblasts was attempted. Three cloned piglets were produced
      from the first round of SCNT, including one stillborn and two who died
      immediately after birth due to respiratory distress syndrome and cardiac
      dysfunction. Among the three piglets, two were confirmed to be alphaGT gene
      targeted. Fibroblasts derived from postmortem ear skin biopsies were used as
      nuclear donor cells for the second round of SCNT, and a piglet was produced. As
      expected, PCR and Southern analyses confirmed that the piglet produced from
      recloning was alphaGT gene-targeted. Currently, the piglet is fourteen months of
      age, and no overt health problems have been observed. Results from the present
      study demonstrate that loss of an invaluable animal, such as a gene-targeted
      miniature pig, may be rescued by recloning, with assurance of the desired genetic
      modification.

PMID- 21196044
TI  - Does supplementing dairy cows with beta-carotene during the dry period affect
      postpartum ovarian activity, progesterone, and cervical and uterine involution?
AB  - beta-carotene is the main natural precursor of vitamin A and plays an important
      role in reproductive efficiency and immune function in dairy cows. The objective
      of this study was to investigate whether a supplement of beta-carotene given
      during the dry period is able to 1) increase blood concentrations of beta
      carotene postpartum, 2) improve ovarian function and progesterone production, and
      3) enhance uterine involution and uterine health. This study was conducted using
      40 Holstein cows. On the day of drying-off, cows were allocated to one of two
      dietary treatments: control diet (C, n = 20) or control diet plus 1g/d beta
      carotene (BC, n = 20). The beta-carotene supplement was given individually to the
      cows until calving. Blood samples were obtained regularly before and after
      calving from the cows to measure the concentrations of beta-carotene. The
      diameters of the cervix and uterine horns were measured regularly using
      ultrasonography. Endometrial cytology samples were acquired from the cervix and
      uterus to determine uterine health. Milk samples were obtained three times per
      week for progesterone assay. Additional blood samples were taken on the day of
      calving, 7 and 21 days postpartum to determine the plasma concentrations of amino
      acids. Blood concentrations of beta-carotene were not different before the start
      of the experiment (C, 3.03 +/- 0.22 mg/L vs BC, 3.12 +/- 0.22 mg/L, P > 0.05).
      Blood concentrations of beta-carotene in the BC group peaked (7.45 +/- 0.24 mg/L)
      1 month after drying-off while the concentrations in the C group remained
      constant. beta-carotene concentrations then decreased in both groups. The
      difference in blood concentrations of beta-carotene between groups became
      significant 2 weeks after the start of the supplement until 2 weeks postpartum.
      There was no significant difference in the interval from calving to ovulation
      between groups (C, 27.8 +/- 3.46 d vs BC, 35.8 +/- 3.55 d, P > 0.05). The dietary
      supplement of beta-carotene during the dry period had no effect on ovarian
      activity, progesterone production, cervix and uterine horn diameters. Plasma
      concentrations of hydroxyproline in the BC group were higher than in the C group
      on day 21 postpartum (BC, 20.8 +/- 1.33 MUmol/L vs C, 15.0 +/- 1.33 MUmol/L; P <
      0.01). On day 28 postpartum the percentage of neutrophils in the BC group was
      lower than in the C group (cervical smear; C, 21.0 +/- 3.22% vs BC, 9.7 +/-
      3.14%, P < 0.05 and uterine smear; C, 32.0 +/- 3.86% vs BC, 20.9 +/- 3.76%, P <
      0.05). In the present experiment a dietary supplement of beta-carotene had no
      effect on ovarian activity. However, due to effects of beta-carotene on
      hydroxyproline profiles and their potential relationship with uterine function we
      speculate that uterine involution may have been more complete and that uterine
      inflammation may have been reduced in cows which received the beta-carotene
      compared to controls.

PMID- 21196045
TI  - Expression and functional implications of peroxisome proliferator-activated
      receptor gamma (PPARgamma) in canine reproductive tissues during normal pregnancy
      and parturition and at antiprogestin induced abortion.
AB  - PPARgamma is a nuclear hormone receptor of the PPAR family of transcription
      factors closely related to the steroid hormone receptors serving multiple roles
      in regulating reproductive function. Endogenous factors from the arachidonic acid
      metabolites group serve as ligands for PPARs. PPARgamma modifies the
      steroidogenic capacity of reproductive tissues and has been defined as a key
      mediator of biological actions of progesterone receptor in granulosa cells; it
      modulates biochemical and morphological placental trophoblast differentiation
      during implantation and placentation. However, no such information is available
      for the dog. Hence, the expression and possible functions of PPARgamma were
      assessed in corpora lutea (CL) and utero/placental (Ut/Pl) compartment collected
      from bitches (n = 3 to 5) on days 8 to 12 (pre-implantation), 18 to 25 (post
      implantation), 35 to 40 (mid-gestation) of pregnancy and at prepartal luteolysis.
      Additionally, 10 mid-pregnant bitches were treated with the antiprogestin
      Aglepristone [10mg/Kg bw (2x/24h)]; ovariohysterectomy was 24h and 72 h after the
      2nd treatment. Of the two PPARgamma isoforms, PPARgamma1 was the only isoform
      clearly detectable in all canine CL and utero/placental samples. The luteal
      PPARgamma was upregulated throughout pregnancy, a prepartal downregulation was
      observed. Placental expression of PPARgamma was elevated after implantation and
      at mid-gestation, followed by a prepartal downregulation. All changes were more
      pronounced at the protein-level suggesting that the PPARgamma expression may be
      regulated at the post-transcriptional level. Within the CL PPARgamma was
      localized to the luteal cells. Placental expression was targeted solely to the
      fetal trophoblast cells; a regulatory role of PPARgamma in canine placental
      development possibly through influencing the invasion of fetal trophoblast cells
      is suggested. Treatment with Aglepristone led to downregulation of PPARgamma in
      either compartment, implying the functional interrelationship with progesterone
      receptor.

PMID- 21196046
TI  - The use of coarser taxonomy in the detection of long-term changes in polychaete
      assemblages.
AB  - Taxonomic Sufficiency (TS) has been proposed as a short-cut method to quantify
      changes of biological assemblages in environmental monitoring. However, issues
      about the efficacy of taxonomic surrogates in depicting long-term temporal
      patterns of marine assemblages are still scant. Here we report on the adoption of
      TS combined with data transformations to describe patterns of North Adriatic
      polychaete assemblages through 20 years. Univariate and multivariate analyses
      revealed large spatial-temporal variation characterizing the assemblages. The
      efficiency to discriminate between the two research periods (1990-1994 vs. 2004
      2008) was reduced when data were analyzed at family and order level leading to
      misinterpreting the sources of assemblage variation. Further information was lost
      with data transforms. Families may represent appropriate assemblages' descriptors
      in long-term monitoring, but using TS coupled with data transformations could
      lead to hazardous loss of information. We suggest that periodical analysis at
      fine taxonomic level should be routinely alternated to long-term monitoring based
      on TS in order to check its effectiveness.

PMID- 21196048
TI  - Vasopressin induces human mesangial cell growth via induction of vascular
      endothelial growth factor secretion.
AB  - Vasoactive hormones, growth factors, and cytokines are important in promoting
      mesangial cell growth, a characteristic feature of many glomerular diseases.
      Vascular endothelial growth factor (VEGF) is an endothelial mitogen and promoter
      of vascular permeability that is constitutively expressed in human glomeruli, but
      its role in the kidney is still unclear. In the present study, we investigated
      the ability of vasopressin (AVP) to stimulate VEGF secretion by and correlation
      with AVP-induced cell growth in human mesangial cells. AVP caused time- and
      concentration-dependent increases in VEGF secretion from human mesangial cells,
      which was in turn potently inhibited by a V(1A) receptor-selective antagonist,
      confirming that this secretion is a V(1A) receptor-mediated event. VEGF also
      induced mesangial cell growth which was completely inhibited on administration of
      an anti-VEGF neutralizing antibody. Further, AVP-induced mesangial cell growth
      was completely abolished by the V(1A) receptor-selective antagonist and partially
      inhibited by an anti-VEGF neutralizing antibody. These results suggest that AVP
      stimulates VEGF secretion by human mesangial cells via V(1A) receptors. This
      secreted VEGF may function as an autocrine hormone to regulate mesangial cell
      growth, a mechanism by which AVP might contribute to progressive glomerular
      diseases such as diabetic nephropathy.

PMID- 21196047
TI  - Ruthenium-catalyzed photo cross-linking of fibrin-based engineered tissue.
AB  - Most cross-linking methods utilize chemistry or physical processes that are
      detrimental to cells and tissue development. Those that are not as harmful often
      do not provide a level of strength that ultimately meets the required
      application. The purpose of this work was to investigate the use of a ruthenium
      sodium persulfate cross-linking system to form dityrosine in fibrin-based
      engineered tissue. By utilizing the tyrosine residues inherent to fibrin and cell
      deposited proteins, at least 3-fold mechanical strength increases and 10-fold
      stiffness increases were achieved after cross-linking. This strengthening and
      stiffening effect was found to increase with culture duration prior to cross
      linking such that physiologically relevant properties were obtained. Fibrin was
      not required for this effect as demonstrated by testing with collagen-based
      engineered tissue. Cross-linked tissues were implanted subcutaneously and shown
      to have minimal inflammation after 30 days, similar to non-cross-linked controls.
      Overall, the method employed is rapid, non-toxic, minimally inflammatory, and is
      capable of increasing strength and stiffness of engineered tissues to
      physiological levels.

PMID- 21196049
TI  - A standardized conversion of IgG antibody to bispecific form with inversely
      altered affinities for Fcgamma-receptors II and III.
AB  - This work aims to enhance killing of antibody-coated human tumor cells by
      altering the antibody's affinity for two effector-cell Fcgamma-receptors
      (FcgammaR). Affinity for the activating FcgammaRIII is raised, affinity for the
      inhibitory FcgammaRIIB is reduced, with the ratio between the two association
      constants increasing >1000-fold. We use as a standard tool the Fab'gamma from a
      monoclonal antibody specific for human FcgammaRIII. This Fab'gamma module is
      bonded to an IgG antibody by a tandem thioether link running between cysteine
      residues in the hinge vicinity of each protein, thus forming a bispecific FabIgG
      construct. Simultaneously, effector function of the IgG module is adjusted by
      leaving its hinge open and adding negative charges. FabIgG constructs derived
      from the chimeric IgG1 antibody rituximab show the following properties. (1) The
      titer for antibody-dependent cellular cytotoxicity is enhanced by 12-100-fold,
      reflecting the affinity of the Fab'gamma module for effector-cell FcgammaRIII.
      (2) Two functions of the construct's Fcgamma, activation of complement and
      prolonged metabolic survival, are moderately reduced. (3) In contrast, affinities
      of the Fcgamma for all FcgammaR are severely reduced, with two anticipated
      consequences. First, attacks by macrophages on antibody-coated cells are favored
      by reduced engagement of the inhibitory FcgammaRIIB. Second, reduced engagement
      of activating FcgammaR by the Fcgamma lowers the probability of untoward
      crosslinkings of FcgammaR, which have been shown to provoke toxicity. If the
      Fab'gamma module possesses human constant regions, the linkage strategy requires
      prior genetic deletion of at least one cysteine residue. With both Fab'gamma and
      IgG modules available, FabIgG can be prepared in 35 h.

PMID- 21196050
TI  - Cognitive impairment in fatigue and sleepiness associated conditions.
AB  - Although relating to very different concepts, sleepiness and fatigue are often
      confounded. However, both fatigue-associated conditions such as the chronic
      fatigue syndrome (CFS) and sleepiness-associated conditions such as the sleep
      apnea-hypopnea syndrome (SAHS) are associated with cognitive impairment with
      impaired attention, concentration and memory performances. Fifteen pure CFS
      patients, without primary sleep disorders or clinically relevant sleepiness, were
      compared to 15 untreated SAHS patients, without clinically relevant fatigue, and
      to 16 healthy controls of similar age. The auditory verbal learning test (AVLT),
      digit span, digit symbol and finger tapping test (FTT) were used as cognitive and
      behavioural measures. In addition we assessed daytime EEG spectral power and P300
      evoked potentials. With exception for the digit span, all tests showed lower
      performances in patient groups. Recall on the AVLT did not differ between the two
      patient groups, but the digit and symbol spans showed more severe impairment in
      SAHS patients. Psychomotor performance on the FTT presented with slower hit rates
      in SAHS than in CFS. EEG theta power was highest in CFS patients. P300 latencies
      and amplitudes did not differ between groups. Fatigue- and sleepiness-associated
      conditions can both present with significant and objective impairment of
      cognitive functioning and behavioural motor performance. In our sample cognitive
      impairment and psychomotor performance were worse when associated to sleepiness
      in SAHS than with fatigue in CFS.

PMID- 21196051
TI  - Remission after first-episode schizophrenia: results of a long-term follow-up.
AB  - The aim of this study was to identify the rate and predictors of remission after
      first episode of schizophrenia (FES). Ninety-three FES patients were followed for
      at least 12 months and up to 12 years (mean=58.4 months) including monthly
      assessments with the Brief Psychiatric Rating Scale-Expanded (BPRS), the Scale
      for the Assessment of Positive Symptoms (SAPS), and Scale for the Assessment of
      Negative Symptoms (SANS). We also administered the Premorbid Adjustment Scale
      (PAS). We used the remission criteria recently defined by Andreasen et al.
      (2005). Fifty-six (59.5%) patients met the remission criteria in the first 24
      months of the follow-up period, but 40 (71.5%) of these patients could not
      maintain their status. However, 23 (57%) of these patients later met the
      remission criteria again. The remission group patients achieved a higher rate of
      employment both in the first year and overall. In the logistic regression
      analysis, lower negative and higher positive symptoms at admission, lower
      positive symptoms at month 3 of the follow-up, medication compliance in the first
      6 months, and occupational status during the last month before admission were
      found related to remission status. Our findings suggest that the remission group
      has advantages in terms of occupational status and symptom severity compared with
      their counterparts who did not achieve or maintain a state of remission.

PMID- 21196052
TI  - Depressive symptoms evaluated by the Calgary Depression Scale for Schizophrenia
      (CDSS): genetic vulnerability and sex effects.
AB  - The present study compares the occurrence of depressive symptoms evaluated by the
      Calgary Depression Scale for Schizophrenia (CDSS) in patients of Multiplex (MS)
      and Simplex Schizophrenia families (SS). The Positive and Negative Syndrome Scale
      (PANSS) was used to evaluate psychopathology. A total of 206 paranoid
      schizophrenia patients were studied according DSM-IV criteria. The Family
      Interview for Genetic Studies (FIGS) was used to study the families. A result in
      the FIGS for a positive family history of schizophrenia was referred as MS
      (patients); its lack as SS (patients). CDSS scores were compared among MS and SS
      patients and possible sex differences intra- and inter-groups were explored. In
      the analysis of our sample (30) 19% of the total persons with schizophrenia group
      was depressed. The depressive symptoms measured by the CDSS were higher in
      females and the MS males group. Males from MS group showed more depressive
      symptoms than males from SS group. No differences with females from both groups
      were found. Findings in this study underscore the importance of gender and family
      history in understanding the heterogeneity of schizophrenia. This study suggests
      that sex and familiar history are important to consider in studying depressive
      symptoms.

PMID- 21196053
TI  - Expressed sequence identification and characterization of the cDNA for
      interleukin-4 from the mitogen-stimulated lymphoid tissue of a marsupial,
      Macropus eugenii.
AB  - Very few cytokines that are important to the understanding of T helper cell
      function are characterized in marsupials. Expression of a 645 bp cDNA product
      that codes for a predicted Interleukin-4 peptide of 157 amino acids was detected
      in the lymph node tissues of Macropus eugenii, the tammar wallaby. Using Rapid
      Amplification of cDNA Ends, both 5'- and 3'-untranslated regions were identified
      and a polyadenylation signal and three mRNA instability motifs associated with
      secreted cytokine molecules were also present. The translated cDNA sequence has a
      putative signal peptide of 24 amino acids, a predicted secondary structure that
      is consistent with the short-chain alpha-helical cytokine family and 82%
      conservation of residues associated with the Interleukin-4 family sequence motif.
      Comparisons of wallaby nucleotide and predicted peptide sequences with the coding
      domains of other vertebrate species demonstrate the diversity within this gene
      family; with nucleotide and amino acid identities of 74% and 59% with opossum,
      52% and 32% with human and 38% and 19% with chicken homologues respectively.
      Despite these differences in sequence conservation, the putative Macropus eugenii
      Interleukin-4 mature peptide contains conserved structural motifs and predicted
      receptor-binding residues that suggest that it may retain functional properties
      associated with this important Th2 cytokine in other mammals.

PMID- 21196055
TI  - Atrial tachyarrhythmias late after Fontan operation are related to increase in
      mortality and hospitalization.
AB  - BACKGROUND: Atrial tachyarrhythmias are a known complication late after Fontan
      operation. Limited information is available on their prognostic value. METHODS:
      All patients with previous Fontan operation followed at our institution since
      1999 were identified from the electronic database and included in this study.
      Demographic and clinical characteristics including history of atrial
      tachyarrhythmias were recorded at the earliest full clinical assessment and
      patients were followed thereafter for all-cause mortality and hospitalization.
      RESULTS: A total of 98 patients, mean age 31.5 +/- 8.9 years, 43.8% male, 31.6%
      with a total cavopulmonary connection (TCPC) were identified. A history of atrial
      tachyarrhythmia was present at baseline in 60.2% of patients who were older (33.0
      +/- 8.3 vs 29.1 +/- 9.4 years, p=0.002), less likely to have a TCPC (13.5% vs
      58.9%, p<0.001), and more symptomatic in terms of NYHA class (51.9% vs 26.7%,
      p=0.007) compared to arrhythmia-free patients. During a median follow-up of 6.7
      years 18 patients died and 64 patients were hospitalized. Even after adjustment
      for baseline clinical characteristics, atrial tachyarrhythmia was an independent
      predictor of death (propensity score adjusted HR 9.35, 95% CI: 1.10-79.18,
      p=0.04, c-statistic 0.88) and composite of death or hospitalization (propensity
      score adjusted HR 5.00, 95% CI: 2.47-10.09, p<0.0001). CONCLUSIONS: In adult
      patients with a Fontan-type operation, the presence of atrial tachyarrhythmias is
      associated with higher morbidity and mortality at mid-term follow-up. Whether
      early arrhythmia targeting intervention may improve clinical outcome needs to be
      studied in a prospective manner.

PMID- 21196054
TI  - Temporal coherence and attention in auditory scene analysis.
AB  - Humans and other animals can attend to one of multiple sounds and follow it
      selectively over time. The neural underpinnings of this perceptual feat remain
      mysterious. Some studies have concluded that sounds are heard as separate streams
      when they activate well-separated populations of central auditory neurons, and
      that this process is largely pre-attentive. Here, we argue instead that stream
      formation depends primarily on temporal coherence between responses that encode
      various features of a sound source. Furthermore, we postulate that only when
      attention is directed towards a particular feature (e.g. pitch) do all other
      temporally coherent features of that source (e.g. timbre and location) become
      bound together as a stream that is segregated from the incoherent features of
      other sources.

PMID- 21196056
TI  - Swinging without feeling.

PMID- 21196057
TI  - Comparative analysis of coronary artery disease assessed by coronary CT
      angiography between patients with type 2 diabetes mellitus and non-diabetic
      patients.

PMID- 21196058
TI  - Socioeconomic risk factor aggregation and long-term incidence of ischemic stroke
      in patients after first acute myocardial infarction.
AB  - BACKGROUND: Low socioeconomic status (SES) has been associated with increased
      cardiovascular risk. However, the association between SES and stroke incidence in
      patients with acute myocardial infarction (AMI) has not been studied. We assessed
      the association between a multidimensional SES construct and long-term ischemic
      stroke incidence after AMI in a prospective community-based cohort study.
      METHODS: A total of 1261 consecutive patients aged <= 65 years discharged after
      first AMI from 8 hospitals in central Israel in 1992-1993 were followed for
      ischemic stroke for a mean (SD) period of 11 (4) years. The number of unfavorable
      SES factors, including lower than average family income, <= 8 years of education,
      unemployment, and absence of a steady partner, was the primary exposure. We
      estimated the directly adjusted cumulative incidence of stroke treating non
      stroke death as a competing event using the Fine and Gray model for a
      subdistribution function. RESULTS: Low SES was associated with older age, female
      sex, higher risk factor prevalence, increased AMI severity and inferior
      treatment. Ischemic stroke was diagnosed in 142 patients. The adjusted cumulative
      incidence of ischemic stroke gradually increased with the number of unfavorable
      SES factors. The multivariable adjusted HRs (95% confidence intervals) for
      ischemic stroke were 1.5(0.9-2.4), 2.0(1.2-3.2) and 2.1(1.2-3.6) in patients with
      1, 2 and >= 3 unfavorable SES factors respectively, compared with those with
      none. CONCLUSIONS: Our data support a dose-response relationship between SES and
      stroke risk after AMI and suggest a multidimensional vulnerability related to
      SES. These findings should be considered in planning secondary prevention
      strategies post-AMI.

PMID- 21196059
TI  - Contemporary theories of 1/f noise in motor control.
AB  - 1/f noise has been discovered in a number of time series collected in
      psychological and behavioral experiments. This ubiquitous phenomenon has been
      ignored for a long time and classical models were not designed for accounting for
      these long-range correlations. The aim of this paper is to present and discuss
      contrasted theoretical perspectives on 1/f noise, in order to provide a
      comprehensive overview of current debates in this domain. In a first part, we
      propose a formal definition of the phenomenon of 1/f noise, and we present some
      commonly used methods for measuring long-range correlations in time series. In a
      second part, we develop a theoretical position that considers 1/f noise as the
      hallmark of system complexity. From this point of view, 1/f noise emerges from
      the coordination of the many elements that compose the system. In a third part,
      we present a theoretical counterpoint suggesting that 1/f noise could emerge from
      localized sources within the system. In conclusion, we try to draw some lines of
      reasoning for going beyond the opposition between these two approaches.

PMID- 21196060
TI  - Effects of yogurt starter cultures on the survival of Lactobacillus acidophilus.
AB  - Recognized to confer health benefits to consumers, probiotics such as
      Lactobacillus acidophilus are commonly incorporated into fermented dairy products
      worldwide; among which yogurt is a popular delivery vehicle. To materialize most
      of the putative health benefits associated with probiotics, an adequate amount of
      viable cells must be delivered at the time of consumption. However, the loss in
      their viabilities during refrigerated storage has been demonstrated previously.
      This study focused on the effects of yogurt starter cultures on the survival of
      five strains of L. acidophilus, with emphases on low pH and acid production.
      Differential survival behavior between L. acidophilus strains was further
      analyzed. To this end, viable cell counts of L. acidophilus were determined
      weekly during 4 degrees C storage in various types of yogurts made with
      Streptococcus thermophilus alone, L. delbrueckii ssp. bulgaricus alone, both
      species of the starter cultures, or glucono-delta-lactone (GDL). All yogurt
      types, except for pasteurized yogurts, were co-fermented with L. acidophilus.
      Yogurt filtrate was analyzed for the presence of any inhibitory substance and for
      the amount of hydrogen peroxide. Multiplication of L. acidophilus was not
      affected by the starter cultures as all strains reached high level on day 0 of
      the storage period. Throughout the 28-day storage period, cell counts of L.
      acidophilus PIM703 and SBT2062 remained steady (~6 * 10(7)CFU/g) in yogurts made
      with both starter cultures, whereas those of ATCC 700396 and NCFM were reduced by
      a maximum of 3 and 4.6 logs, respectively. When starter cultures were replaced by
      GDL, all strains survived well, suggesting that a low pH was not a critical
      factor dictating their survival. In addition, the filtrate collected from yogurts
      made with starter cultures appeared to have higher inhibitory activities against
      L. acidophilus than that made with GDL. The presence of viable starter cultures
      was necessary to adversely affect the survival of some strains, as pasteurized
      yogurts had no effect on their survival. In particular, the inhibitory effect
      exerted by L. delbrueckii ssp. bulgaricus on L. acidophilus NCFM was highly
      pronounced than by S. thermophilus, nevertheless, the same effect was not
      observed on SBT2062. The inhibition against stationary-phase NCFM cells might be
      caused by the elevated level of hydrogen peroxide produced by L. delbrueckii ssp.
      bulgaricus. Delineating factors driving the differences in survival trait among
      probiotic strains will lead to a more efficacious delivery of health benefits in
      fermented dairy products through targeted technological interventions.

PMID- 21196061
TI  - The evolution of the worldwide leaf economics spectrum.
AB  - The worldwide leaf economic spectrum (WLES) is a strikingly consistent pattern of
      correlations among leaf traits. Although the WLES effectively summarizes
      variation in plant ecological strategies, little is known about its evolution. We
      reviewed estimates of natural selection and genetic variation for leaf traits to
      test whether the evolution of the WLES was limited by selection against unfit
      trait combinations or by genetic constraints. There was significant selection for
      leaf traits on both ends of the WLES spectrum, as well as significant genetic
      variation for these traits. In addition, genetic correlations between WLES traits
      were variable in strength and direction. These data suggest that genetic
      constraints have had a smaller role than selection in the evolution of the WLES.

PMID- 21196062
TI  - Strontium migration in a crystalline medium: effects of the presence of bentonite
      colloids.
AB  - The effects of bentonite colloids on strontium migration in fractured crystalline
      medium were investigated. We analyzed first the transport behaviour of bentonite
      colloids alone at different flow rates; then we compared the transport behaviour
      of strontium as solute and of strontium previously adsorbed onto stable bentonite
      colloids at a water velocity of approximately 7.1.10(-6)m/s-224m/yr. Experiments
      with bentonite colloids alone showed that - at the lowest water flow rate used in
      our experiments (7.1.10(-6)m/s) - approximately 70% of the initially injected
      colloids were retained in the fracture. Nevertheless, the mobile colloidal
      fraction, moved through the fracture without retardation, at any flow rate.
      Bentonite colloids deposited over the fracture surface were identified during
      post-mortem analyses. The breakthrough curve of strontium as a solute, presented
      a retardation factor, R(f)~6, in agreement with its sorption onto the granite
      fracture surface. The breakthrough curve of strontium in the presence of
      bentonite colloids was much more complex, suggesting additional contributions of
      colloids to strontium transport. A very small fraction of strontium adsorbed on
      mobile colloids moved un-retarded (R(f)=1) and this fraction was much lower than
      the expected, considering the quantity of strontium initially adsorbed onto
      colloids (90%). This behaviour suggests the hypothesis of strontium sorption
      reversibility from colloids. On the other hand, bentonite colloids retained
      within the granite fracture played a major role, contributing to a slower
      strontium transport in comparison with strontium as a solute. This was shown by a
      clear peak in the breakthrough curve corresponding to a retardation factor of
      approximately 20.

PMID- 21196063
TI  - First transgenic rat model developing progressive cortical neurofibrillary
      tangles.
AB  - Neurofibrillary degeneration induced by misfolded protein tau is considered to be
      one of the key pathological hallmarks of Alzheimer's disease (AD). In the present
      study, we have introduced a novel transgenic rat model expressing a human
      truncated tau that encompasses 3 microtubule binding domains (3R) and a proline
      rich region (3R tau151-391). The transgenic rats developed progressive age
      dependent neurofibrillary degeneration in the cortical brain areas.
      Neurofibrillary tangles (NFTs) satisfied several key histological criteria used
      to identify neurofibrillary degeneration in human Alzheimer's disease including
      argyrophilia, Congo red birefringence, and Thioflavin S reactivity.
      Neurofibrillary tangles were also identified with antibodies used to detect
      pathologic tau in the human brain, including DC11, recognizing an abnormal tau
      conformation and antibodies that are specific for hyperphosphorylated forms of
      tau protein. Moreover, neurofibrillary degeneration was characterized by
      extensive formation of sarkosyl insoluble tau protein complexes consisting of rat
      endogenous and truncated tau species. Interestingly, the transgenic rats did not
      show neuronal loss either in the cortex or in the hippocampus. We suggest that
      novel transgenic rat model for human tauopathy represents a valuable tool in
      preclinical drug discovery targeting neurofibrillary degeneration of Alzheimer's
      type.

PMID- 21196065
TI  - Ultrastructural alterations of Alzheimer's disease paired helical filaments by
      grape seed-derived polyphenols.
AB  - Abnormal folding of the microtubule-associated protein tau leads to aggregation
      of tau into paired helical filaments (PHFs) and neurofibrillary tangles, the
      major hallmark of Alzheimer's disease (AD). We have recently shown that grape
      seed polyphenol extract (GSPE) reduces tau pathology in the TMHT mouse model of
      tauopathy (Wang et al., 2010). In the present studies we assessed the impact of
      GSPE exposure on the ultrastructure of PHFs isolated from Alzheimer's disease
      brain. Transmission electron microscopy revealed that GSPE induced profound dose-
      and time-dependent alterations in the morphology of PHFs with partial
      disintegration of filaments. Filaments showed ~2-fold enlargement in width and
      displayed numerous protrusions and splayed ends consistent with unfolding of tau
      and diminished structural stability. In addition, GSPE induced a reduction in
      immunogold labeling with antibodies against the C-terminal half (12E8, PHF-1) and
      the middle region of tau (AT8, Tau5, pSer214 tau, and AT180) but not the C
      terminal end (Tau46). In comparison, labeling of N-terminus (Alz50) was enhanced.
      It is unlikely that alterations in immunogold labeling were due to biochemical
      alterations, e.g., protein phosphatase or proteolytic activities potentially
      stimulated by GSPE, because western blotting studies have shown the preservation
      of full length polypeptides of tau and their phospho-epitopes in GSPE-treated
      samples. The GSPE mechanism may include a noncovalent interaction of polyphenols
      with proline residues in the proline-rich domain of tau, with Pin1 sites at P213
      and P232 most seriously affected as judged by suppression of labeling.
      Collectively, our results suggest that GSPE has a significant potential for
      therapeutic development by neutralizing phospho-epitopes and disrupting
      fibrillary conformation leading to disintegration of PHFs.

PMID- 21196066
TI  - [Introduction of the "Up-date" series. Hemodynamic monitoring in critically ill
      patient].

PMID- 21196064
TI  - Amyloid precursor protein (APP) processing genes and cerebrospinal fluid APP
      cleavage product levels in Alzheimer's disease.
AB  - The aim of this exploratory investigation was to determine if genetic variation
      within amyloid precursor protein (APP) or its processing enzymes correlates with
      APP cleavage product levels: APPalpha, APPbeta or Abeta42, in cerebrospinal fluid
      (CSF) of cognitively normal subjects or Alzheimer's disease (AD) patients.
      Cognitively normal control subjects (n = 170) and AD patients (n = 92) were
      genotyped for 19 putative regulatory tagging SNPs within 9 genes (APP, ADAM10,
      BACE1, BACE2, PSEN1, PSEN2, PEN2, NCSTN and APH1B) involved in the APP processing
      pathway. SNP genotypes were tested for their association with CSF APPalpha,
      APPbeta, and Abeta42, AD risk and age-at-onset while taking into account age,
      gender, race and APOE epsilon4. After adjusting for multiple comparisons, a
      significant association was found between ADAM10 SNP rs514049 and APPalpha
      levels. In controls, the rs514049 CC genotype had higher APPalpha levels than the
      CA, AA collapsed genotype, whereas the opposite effect was seen in AD patients.
      These results suggest that genetic variation within ADAM10, an APP processing
      gene, influences CSF APPalpha levels in an AD specific manner.

PMID- 21196067
TI  - CHARGE syndrome and CHD7 gene mutation.

PMID- 21196068
TI  - A pilot study on conducting mobile learning activities for clinical nursing
      courses based on the repertory grid approach.
AB  - In clinical nursing courses, students are trained to identify the status of the
      target patients. The mastery of such ability and skills is very important since
      patients frequently need to be cared for immediately. In this pilot study, a
      repertory grid-oriented clinical mobile learning system is developed for a
      nursing training program. With the assistance of the mobile learning system, the
      nursing school students are able to learn in an authentic learning scenario, in
      which they can physically face the target patients, with the personal guidance
      and supplementary materials from the learning system to support them. To show the
      effectiveness of this innovative approach, an experiment has been conducted on
      the "respiratory system" unit of a nursing course. The experimental results show
      that the innovative approach is helpful to students in improving their learning
      achievements. Moreover, from the questionnaire surveys, it was found that most
      students showed favorable attitudes toward the usage of the mobile learning
      system and their participation in the training program.

PMID- 21196069
TI  - Analysis of vertical ground reaction force variables during a Sit to Stand task
      in participants recovering from a hip fracture.
AB  - BACKGROUND: A Sit to Stand task following a hip fracture may be achieved through
      compensations (e.g. bilateral arms and uninvolved lower extremity), not
      restoration of movement strategies of the involved lower extremity. The primary
      purpose was to compare upper and lower extremity movement strategies using the
      vertical ground reaction force during a Sit to Stand task in participants
      recovering from a hip fracture to control participants. The secondary purpose was
      to evaluate the correlation between vertical ground reaction force variables and
      validated functional measures. METHODS: Twenty eight community dwelling older
      adults, 14 who had a hip fracture and 14 control participants completed the Sit
      to Stand task on an instrumented chair designed to measure vertical ground
      reaction force, performance based tests (Timed up and go, Berg Balance Scale and
      Gait Speed) and a self report Lower Extremity Measure. A MANOVA was used to
      compare functional scales and vertical ground reaction force variables between
      groups. Bivariate correlations were assessed using Pearson Product Moment
      correlations. FINDINGS: The vertical ground reaction force variables showed
      significantly higher bilateral arm force, higher uninvolved side peak force and
      asymmetry between the involved and uninvolved sides for the participants
      recovering from a hip fracture (Wilks' Lambda=3.16, P=0.019). Significant
      correlations existed between the vertical ground reaction force variables and
      validated functional measures. INTERPRETATION: Participants recovering from a hip
      fracture compensated using their arms and the uninvolved side to perform a Sit to
      Stand. Lower extremity movement strategies captured during a Sit to Stand task
      were correlated to scales used to assess function, balance and falls risk.

PMID- 21196070
TI  - Design of the Circulation Improving Resuscitation Care (CIRC) Trial: a new state
      of the art design for out-of-hospital cardiac arrest research.
AB  - PURPOSE: Mechanical chest compression devices, such as the AutoPulse((r)), have
      been developed to overcome problems associated with manual CPR (M-CPR). Animal
      and human studies have shown that AutoPulse CPR improves hemodynamic parameters
      over M-CPR. However, human studies conducted in the prehospital setting have
      conflicting results as to the AutoPulse's efficacy in improving survival. The
      Circulation Improving Resuscitation Care (CIRC) Trial is designed to evaluate the
      effectiveness of integrated AutoPulse-CPR (iA-CPR) (i.e., M-CPR followed by
      AutoPulse((r))-CPR) in a randomized controlled trial that addresses
      methodological issues that may have influenced the results of previous studies.
      METHODS: This paper describes the methodology of the CIRC trial. RESULTS: Unlike
      previous trials the CIRC trial studies iA-CPR where emphasis is placed on
      reducing "hands-off" time. The trial has six unique features: (1) training of all
      EMS providers in a standardized deployment strategy that reduces hands-off time
      and continuous monitoring for protocol compliance. (2) A pre-trial simulation
      study of provider compliance with the trial protocol. (3) Three distinct study
      phases (in-field training, run-in, and statistical inclusion) to minimize the
      Hawthorne effect and other biases. (4) Monitoring of the CPR process using either
      transthoracic impedance or accelerometer data. (5) Randomization at the subject
      level after the decision to resuscitate is made to reduce selection bias. (6) Use
      of the Group Sequential Double Triangular Test with sufficient power to determine
      superiority, inferiority, or equivalence. CONCLUSION: This unique, large,
      multicenter study comparing the effectiveness of iA-CPR to M-CPR will contribute
      to the science of the treatment of out-of-hospital cardiac arrest as well as to
      the design of future trials.

PMID- 21196071
TI  - Phytodermatitis caused by Agave americana.

PMID- 21196072
TI  - A project-based system for including farmers in the EU ETS.
AB  - Farmers in the EU do not trade greenhouse gases under the Kyoto agreement. This
      is an empirical puzzle because agriculture is a significant contributor of
      greenhouse gases (GHG) in the EU and may harvest private net gains from trade.
      Furthermore, the US has strongly advocated land-use practices as 'the missing
      link' in past climate negotiations. We argue that farmers have relatively low
      marginal reduction costs and that consequences in terms of the effect on permit
      price and technology are overall positive in the EU Emission Trading System
      (ETS). Thus, we propose a project-based system for including the farming
      practices in the EU ETS that reduces the uncertainty from measuring emission
      reduction in this sector. The system encourages GHG reduction either by
      introducing a new and less polluting practice or by reducing the polluting
      activity. When doing so, farmers will receive GHG permits corresponding to the
      amount of reduction which can be stored for later use or sold in the EU ETS.

PMID- 21196073
TI  - Does varicocele repair improve male infertility? An evidence-based perspective
      from a randomized, controlled trial.
AB  - BACKGROUND: Randomized controlled trials (RCTs) addressing varicocele treatment
      are scarce and have conflicting outcomes. OBJECTIVE: To determine whether
      varicocele treatment is superior or inferior to no treatment in male infertility
      from an evidence-based perspective. DESIGN, SETTING, AND PARTICIPANTS: A
      prospective, nonmasked, parallel-group RCT with a one-to-one concealed-to-random
      allocation was conducted at the authors' institution from February 2006 to
      October 2009. Married men 20-39 yr of age who had experience infertility >=1 yr,
      had palpable varicoceles, and with at least one impaired semen parameter (sperm
      concentration <20 million/ml, progressive motility <50%, or normal morphology
      <30%) were eligible. Exclusions included subclinical or recurrent varicoceles,
      normal semen parameters, and azoospermia. Sample size analysis suggested 68
      participants per arm. INTERVENTION: Participants were randomly allocated to
      observation (the control arm [CA]) or subinguinal microsurgical varicocelectomy
      (the treatment arm [TA]). Semen analyses were obtained at baseline (three
      analyses) and at follow-up months 3, 6, 9, and 12. The mean of each sperm
      parameter at baseline and follow-ups was determined. MEASUREMENTS: We measured
      the spontaneous pregnancy rate (the primary outcome), changes from baseline in
      mean semen parameters, and the occurrence of adverse events (AE-the secondary
      outcomes) during 12-mo follow-up; p<0.05 was considered significant. RESULTS AND
      LIMITATIONS: Analysis included 145 participants (CA: n=72; TA: n=73), with a mean
      age plus or minus standard deviation of 29.3+/-5.7 in the CA and 28.4+/-5.7 in
      the TA (p=0.34). Baseline characteristics in both arms were comparable.
      Spontaneous pregnancy was achieved in 13.9% (CA) versus 32.9% (TA), with an odds
      ratio (OR) of 3.04 (95% confidence interval [CI], 1.33-6.95) and a number needed
      to treat (NNT) of 5.27 patients (95% CI, 1.55-8.99). In CA within-arm analysis,
      none of semen parameters revealed significant changes from baseline (sperm
      concentration [p=0.18], progressive motility [p=0.29], and normal morphology
      [p=0.05]). Conversely, in TA within-arm analysis, the mean of all semen
      parameters improved significantly in follow-up versus baseline (p<0.0001). In
      between-arm analysis, all semen parameters improved significantly in the TA
      versus CA (p<0.0001). No AEs were reported. CONCLUSIONS: Our RCT provided level
      1b evidence of the superiority of varicocelectomy over observation in infertile
      men with palpable varicoceles and impaired semen quality, with increased odds of
      spontaneous pregnancy and improvements in semen characteristics within 1-yr of
      follow-up.

PMID- 21196074
TI  - Effects of the gonadotropin-releasing hormone antagonist ganirelix on normal
      micturition and prostaglandin E(2)-induced detrusor overactivity in conscious
      female rats.
AB  - BACKGROUND: Gonadotropin-releasing hormone (GnRH) antagonists have been reported
      to have beneficial effects on lower urinary tract symptoms in patients with
      benign prostatic hyperplasia. OBJECTIVE: Our aim was to investigate the effects
      of ganirelix, a GnRH receptor antagonist, on bladder function and detrusor
      overactivity (DO) in female rats. DESIGN, SETTING, AND PARTICIPANTS: Female
      Sprague-Dawley rats received 2 wk of daily systemic (0.1 mg/kg) or acute
      intravesical administration (IVES; 0.14 mg/l or 1.4 mg/l) ganirelix or vehicle
      (controls). MEASUREMENTS: Assessments were obtained using cystometry in awake
      rats, organ bath studies, enzyme-linked immunosorbent assay, and western blot
      (WB). RESULTS AND LIMITATIONS: Luteinising hormone levels were lower in rats
      treated systemically with ganirelix than in controls. No differences were
      observed in body or bladder weights. Micturition interval (MI), micturition
      volume (MV), residual volume, and bladder capacity (BC) were similar in both
      groups at baseline. No differences in urodynamic pressure parameters were
      observed between groups at baseline. Intravesical prostaglandin E(2) reduced MI,
      MV, and BC, and it increased basal pressure (BP), threshold pressure (TP), flow
      pressure (FP), and maximum pressure (MP) in all rats. MI, MV, and BC were reduced
      by 43%+/-4%, 50%+/-4%, and 43%+/-4% (controls) versus 22%+/-3%, 23%+/-3%, and
      21%+/-3% (ganirelix-treated rats; p<0.001). TP and FP increased by 38%+/-8% and
      30%+/-4% (controls) versus 16%+/-7% and 16%+/-5% (ganirelix; p<0.05). The maximal
      force of contractions for carbachol was larger in detrusor from ganirelix-treated
      rats (231% vs 177% of 60 mM K+-induced contractions). At 0.14 mg/l, but not 0.14
      mg/l, IVES ganirelix increased MI, MV, and BC and decreased BP, TP, FP, and MP.
      In vitro, ganirelix had no effect on detrusor function. The gonadotropin
      releasing hormone receptor was expressed (by WB) in the bladder mucosa.
      CONCLUSIONS: Systemic treatment with ganirelix counteracted experimental DO in
      female rats. Because bladder preparations from these rats exhibited larger
      contractions to carbachol and because intravesical ganirelix affected both
      micturition intervals and urodynamic pressure profiles, a peripheral site of
      action of ganirelix in the urinary bladder cannot be excluded.

PMID- 21196075
TI  - Exosomes as biomarker treasure chests for prostate cancer.
AB  - CONTEXT: Although progress has been made with regard to types of markers
      (protein, DNA, RNA, and metabolites) and implementation of improved technologies
      (mass spectrometry, arrays, and deep sequencing), the discovery of novel
      biomarkers for prostate cancer (PCa) in complex fluids, such as serum and urine,
      remains a challenge. Meanwhile, recent studies have reported that many cancer
      derived proteins and RNAs are secreted through small vesicles known as exosomes.
      OBJECTIVE: This narrative review describes recent progress in exosome research,
      focusing on the potential role of exosomes as novel biomarkers for PCa. The
      purpose of this review is to acquaint clinicians and researchers in the field of
      urology with the potential role of exosomes as biomarker treasure chests and with
      their clinical value. EVIDENCE ACQUISITION: Medline and Embase entries between
      1966 and September 2010 were searched using the keywords exosomes, microvesicles,
      prostasomes, biomarkers, prostate cancer, and urology. Leading publications and
      articles constructively contributing to exosome research were selected for this
      review. EVIDENCE SYNTHESIS: Exosomes are small vesicles (50-100 nm) secreted by
      almost all tissues; they represent their tissue origin. Purification of prostate-
      and PCa-derived exosomes will allow us to profile exosomes, providing a promising
      source of protein and RNA biomarkers for PCa. This profiling will contribute to
      the discovery of novel markers for the early diagnosis and reliable prognosis of
      PCa. CONCLUSIONS: Although the initial results are promising, further
      investigations are required to assess the clinical value of these exosomes in
      PCa.

PMID- 21196076
TI  - Expression and prognostic relevance of the death receptor CD95 (Fas/APO1) in
      renal cell carcinomas.
AB  - CD95 (Fas/APO1) is one of the best known members of the death receptor family
      which can either mediate apoptosis or activate tumor-promoting pathways. Using a
      tissue microarray we investigated the association between the expression of CD95
      and prognosis in 617 patients with renal cell carcinomas (RCCs). CD95 was
      expressed in the vast majority of RCCs. High CD95 expression was associated with
      lymph node metastasis and correlated negatively with disease-specific survival.
      Multivariate Cox regression analysis confirmed CD95 expression as an independent
      prognostic factor. In conclusion, high CD95 expression is a negative independent
      prognostic factor in RCCs which could be used to identify high-risk patients with
      a poor clinical prognosis.

PMID- 21196077
TI  - Aliphatic and polycyclic aromatic hydrocarbons in the Xihe River, an urban river
      in China's Shenyang City: distribution and risk assessment.
AB  - The characteristics of petroleum hydrocarbons and the risks they pose to the
      ecosystem were studied in the Xihe River, which is an urban river located in
      Shenyang, China. High levels of aliphatic hydrocarbons (AHc) and polycyclic
      aromatic hydrocarbons (PAHs) were observed in the river due to the discharge of
      wastewater from industrial and municipal facilities for a long period of time.
      High-molecular-weight hydrocarbons, including unresolved complex mixtures (UCM)
      of n-alkanes between n-C16 and n-C32 and of PAHs with four to six rings, were the
      dominant hydrocarbons in the river, particularly in suspended particulate matter
      (SPM) and sediments. The AHc was mainly from petrogenic sources, whereas PAHs was
      from both pyrolytic and petrogenic source inputs. Our results suggest that there
      is a high risk of toxicity for the soils and groundwater of the study area. The
      overall toxicity in the sediments can be described using the toxic equivalent
      (TEQ) of dibenzo[a,h]anthracene (DBA) based on benzo(a)pyrene (TEQ(BaP)) and
      dioxins (TEQ(TCDD)) toxic equivalent concentrations. The TEQ values for
      benzo(a)pyrene (TEQ(BaP)) and dioxins (TEQ(TCDD)) presented a consistent
      assessment of sediment PAHs.

PMID- 21196078
TI  - Treating pain with pain: supraspinal mechanisms of endogenous analgesia elicited
      by heterotopic noxious conditioning stimulation.
AB  - While being exposed to an intensive tonic pain stimulus at one area of the body,
      another phasic pain stimulus applied to a remote site is perceived as less
      painful. The neurophysiological basis for this "pain inhibits pain" phenomenon
      has been presumed to be an activation of the spino-bulbo-spinal mechanism termed
      "diffuse noxious inhibitory controls." However, several additional mechanisms
      such as an activation of the descending pain control system may contribute to
      this observation. Here we investigated the underlying supraspinal mechanisms of
      "heterotopic noxious conditioning stimulations" (HNCS), representing this
      specific experimental constellation. We used functional magnetic resonance
      imaging and behavioral recordings in combination with a modified cold-pressor
      task and phasic painful stimuli, and investigated the contribution of endogenous
      opioids to this mechanism using the opioid antagonist naloxone in a double-blind
      crossover design. HNCS led to marked endogenous analgesia and this effect
      correlated positively with the perceived intensity of the tonic painful stimulus.
      Furthermore, HNCS was paralleled by reduced blood oxygen level dependent (BOLD)
      responses in classical pain-responsive regions. Conversely, HNCS led to tonic
      BOLD increases in subregions of the anterior cingulate cortex. The strength of
      functional coupling between the subgenual anterior cingulate cortex and key
      structures of the descending pain control system was enhanced during HNCS, which
      correlated positively with the individual endogenous analgesia during HNCS. These
      effects were in part reversed by naloxone, speaking for the contribution of
      endogenous opioid neurotransmission to this mechanism. Taken together, these
      results demonstrate a substantial contribution of higher-order brain regions to
      the phenomenon of hypoalgesia during HNCS. Functional magnetic resonance imaging
      shows how the human brain is involved in heterotopic noxious conditioning and
      reveals active supraspinal pain modulatory mechanisms during dual pain
      stimulation.

PMID- 21196079
TI  - Influence of headache frequency on clinical signs and symptoms of TMD in subjects
      with temple headache and TMD pain.
AB  - The relationship of the frequency of temple headache to signs and symptoms of
      temporomandibular joint (TMJ) disorders (TMD) was investigated in a subset of a
      larger convenience sample of community TMD cases. The study sample included 86
      painful TMD, nonheadache subjects; 309 painful TMD subjects with varied frequency
      of temple headaches; and 149 subjects without painful TMD or headache for
      descriptive comparison. Painful TMD included Research Diagnostic Criteria for
      Temporomandibular Disorders diagnoses of myofascial pain, TMJ arthralgia, and TMJ
      osteoarthritis. Mild to moderate-intensity temple headaches were classified by
      frequency using criteria based on the International Classification of Headache
      Disorder, 2nd edition, classification of tension-type headache. Outcomes included
      TMD signs and symptoms (pain duration, pain intensity, number of painful
      masticatory sites on palpation, mandibular range of motion), pressure pain
      thresholds, and temple headache resulting from masticatory provocation tests.
      Trend analyses across the painful TMD groups showed a substantial trend for
      aggravation of all of the TMD signs and symptoms associated with increased
      frequency of the temple headaches. In addition, increased headache frequency
      showed significant trends associated with reduced PPTs and reported temple
      headache with masticatory provocation tests. In conclusion, these findings
      suggest that these headaches may be TMD related, as well as suggesting a possible
      role for peripheral and central sensitization in TMD patients.

PMID- 21196080
TI  - In vivo anthelmintic activity of bruceine A and bruceine D from Brucea javanica
      against Dactylogyrus intermedius (Monogenea) in goldfish (Carassius auratus).
AB  - The present study was designated to ascertain the anthelmintic activity of the
      dried fruits of Brucea javanica and to isolate and characterise the active
      constituents. The methanol extract from the fruits of B. javanica showed
      significant anthelmintic activity against Dactylogyrus intermedius (EC(50)
      (median effective concentration) value=49.96 mg l(-1)). Based on this finding,
      the methanol extract was fractionated on silica gel column chromatography in a
      bioassay-guided fractionation affording two known quassinoids showing potent
      activity, bruceine A and bruceine D. Both bruceine A and D exhibited significant
      activity against D. intermedius with EC(50) values of 0.49 mg l(-1) and 0.57 mg
      l(-1), respectively, which were more effective than the positive control,
      mebendazole (EC(50) value=1.25 mg l(-1)). In addition, the 48-h median lethal
      concentration (LC(50)) for bruceine A and D against the host (Carassius auratus)
      was 10.6-fold and 9.7-fold higher than the EC(50) for D. intermedius. These
      results provide evidence that the isolated compounds might be potential sources
      of new anti-parasitic drugs for the control of Dactylogyrus. This is the first
      report on an in vivo anthelmintic investigation for B. javanica against D.
      intermedius.

PMID- 21196082
TI  - Incremental validity of college alcohol beliefs in the prediction of freshman
      drinking and its consequences: a prospective study.
AB  - Osberg et al. (2010) recently developed the College Life Alcohol Salience Scale
      (CLASS), which assesses the extent to which students identify with the college
      drinking culture. Using a prospective design, we explored the incremental and
      predictive validity of the new measure in a sample of 479 college freshmen.
      Scores obtained on the new measure at Time 1 demonstrated strong positive
      associations with concurrently assessed drinking patterns and alcohol
      consequences, as well as those collected at Time 2 1 month later. The college
      alcohol beliefs measured by the CLASS also explained significant additional
      variance in drinking and its consequences at Time 2 beyond that accounted for by
      gender, perceived descriptive and injunctive norms, and positive and negative
      alcohol expectancies. Moreover, CLASS scores predicted typical drinking levels
      and alcohol consequences at Time 2, even when baseline levels of these drinking
      indices were controlled. Potential future lines of research with the CLASS are
      discussed.

PMID- 21196081
TI  - Predictors of initiation and engagement in substance abuse treatment among
      individuals with co-occurring serious mental illness and substance use disorders.
AB  - Research has documented the significant challenges of engaging individuals with
      comorbid serious mental illness (SMI) and substance use disorders (SUDs) in
      substance abuse treatment. To date it is unclear which factors predict treatment
      initiation and engagement in this group of individuals with SUDs. In this study
      we conducted two analyses using data from a randomized trial of substance abuse
      treatment in outpatients with SMI: the first examining predictors (collected
      during screening) of completing an initial intake assessment and the second
      examining predictors (collected during the intake assessment) of becoming engaged
      in treatment. Results indicated that males and those with schizophrenia spectrum
      diagnoses were less likely to complete the intake assessment. Participants who
      reported more positive feelings about their family were more likely to engage in
      substance abuse treatment. Participants who were recently arrested were less
      likely to engage in treatment. Those who met criteria for current drug dependence
      were less likely to engage in treatment. Overall, these findings are a useful
      step in determining factors that predict substance abuse treatment initiation and
      engagement in individuals with SMI and SUDs.

PMID- 21196083
TI  - College students' use of cocaine: results from a longitudinal study.
AB  - College students have high rates of heavy drinking and other risky behaviors, but
      little is known about trends in their use of cocaine. In this longitudinal study
      of 1253 college students at one large, public university in the mid-Atlantic
      region, annual interviews assessed opportunity to use cocaine, cocaine use, and
      DSM-IV criteria for cocaine abuse and dependence. Follow-up rates exceeded 87%
      annually. Data from the first four years of college were analyzed to detect
      changes over time and possible gender differences. By their fourth year of
      college, 36%(wt) of students had been offered cocaine at least once in their
      lifetime, and 13%(wt) had used cocaine. Annual prevalence of cocaine use
      increased significantly over time (4%(wt) in Year 1 to 10%(wt) in Year 4) and
      remained similar across genders. Opportunities to use cocaine were significantly
      more prevalent for males than females during Years 2 through 4. Cocaine use given
      opportunity increased significantly over time for both males and females. Among
      243 cocaine users, females (n=113) had more serious use patterns than males, with
      higher average frequency of use (18.39 vs. 8.83 days during the peak year of use,
      p<.05) and greater likelihood of meeting criteria for cocaine dependence (9.3%
      vs. 2.5%, p<.05). Gender differences in typical cocaine dosage were not apparent.
      College administrators and health providers should be aware of the prevalence of
      cocaine use among student populations and design strategies to address the
      problem.

PMID- 21196084
TI  - Ultrasound velocity and attenuation of porcine soft tissues with respect to
      structure and composition: I. Muscle.
AB  - Ultrasound velocity and attenuation of soft tissues have been widely
      investigated. However, few studies completely covered considerable variations of
      both, structure and composition. The aim of this study was to collect acoustic
      reference data of porcine Longissimus muscle and associate them with
      compositional traits. In addition, measurements were conducted on fresh, formalin
      fixed, and frozen-thawed samples to evaluate the effect of processing on
      ultrasound parameters and comparisons with earlier investigations. Measurement
      conditions (temperature and fibre orientation) were realised close to hanging
      carcasses conditions. Sound velocity ranged from 1617 +/- 6 to 1622 +/- 5 ms(-1),
      while attenuation mostly ranged from 1.0 +/- 0.3 to 1.2 +/- 0.3 dB MHz(-1)cm(-1).
      Only formalin fixed samples showed significantly higher attenuation (2.2 +/- 0.6
      dB MHz(-1)cm(-1)). Highest correlations have been observed between intramuscular
      fat and attenuation (up to r = .7). The obtained results are anticipated to
      improve ultrasound based estimation of the intramuscular fat of pig muscle on
      intact carcasses.

PMID- 21196085
TI  - Carcass maturity and dicationic salts affect preblended, low-fat, low-sodium
      restructured beef.
AB  - Preblending A- and C-maturity muscles with MgCl(2) and/or CaCl(2) was
      investigated in low-fat, low-sodium restructured beef. Products were formulated
      to contain: 1) 80% chunks, preblended 12h with 0.05% MgCl(2), 0.05% CaCl(2), or a
      combination of each (0.1%) and 0.4% sodium tripolyphosphate (STPP) and 2) 20%
      mince preblended 12h with 0.05% of each dicationic salt or the combination of
      dicationic salts (0.1%), 0.4% STPP, and 1.0% NaCl. This formulation achieved a
      raw product NaCl content of 0.2%. Additionally, a control was formulated with
      chunks and mince that contained no dicationic salt. CaCl(2) decreased raw and
      cooked pH and cook yield, and increased cohesiveness; whereas, MgCl(2) increased
      cook yield and myosin solubility. Total protein solubility was not affected by
      muscle maturity or dicationic treatment. Myosin solubility of the combination
      treatment was greater for C-maturity muscle (57 months) compared to A-maturity
      muscle (20 months) formulations. Control, C-maturity muscle treatments contained
      more insoluble and total collagen (p < 0.05), and these treatments were more
      cohesive (p < 0.05) than control, A-maturity treatments. The combination of
      CaCl(2) and MgCl(2) increased hardness of A-maturity products, but it decreased
      hardness of C-maturity products. In addition to increasing hardness of A-maturity
      products, the combination treatment lowered (p < 0.05) cook yield for these
      products.

PMID- 21196086
TI  - Effects of porcine MC4R and LEPR polymorphisms, gender and Duroc sire line on
      economic traits in Duroc * Iberian crossbred pigs.
AB  - Polymorphisms MC4R c.1426 A>G (p.Asp298Asn) and LEPR c.2002 C>T (p.Leu663Phe)
      have been associated in pigs with feed intake, growth and fatness. Our aims were
      to analyze how these polymorphisms influence production and quality traits in
      Duroc * Iberian crossbred pigs, and moreover evaluate how the effects of gender
      and Duroc line were affecting these traits. Significant effects of gender, Duroc
      sire line and LEPR c.2002 C>T mutation, were detected on the main traits. LEPR
      c.2002 T allele increased body weight (2.5 +/- 0.7 kg), backfat thickness (1.5 +/
      0.4mm), loin intramuscular fat (0.7 +/- 0.2 %), and lightness (1.0 +/- 0.3);
      however it was decreasing premium cuts yield (-0.9 +/- 0.2%). Allele c.2002 T
      increased SFA (0.60 +/- 0.12 %), and decreased MUFA (-0.35 +/- 0.12%) and PUFA (
      0.25 +/- 0.06%). No significant effects of MC4R c.1426 A>G SNP were identified. A
      genetic test based on the LEPR c.2002 C>T SNP may be useful to select Duroc sires
      to reduce undesirable heterogeneity of carcasses and premium cuts of crossbred
      animals.

PMID- 21196087
TI  - Ultrasound velocity and attenuation of porcine soft tissues with respect to
      structure and composition: II. Skin and backfat.
AB  - Ultrasound is regarded as a promising method to determine the intramuscular fat
      content of pork loin. At intact carcasses, the signal passes the backfat whose
      ultrasound parameters (sound velocity and attenuation) have not been fully
      investigated. This study intended to collect a dataset of ultrasound parameters
      for individual backfat layers and to elucidate relationships with structural and
      compositional characteristics. In-vitro measurements at 10 MHz were conducted on
      backfat samples of pork carcasses representative for German populations. The
      average sound velocity ranged from 1436 +/- 9 to 1470 +/- 37 ms(-1) for the fat
      layers, and 1682 +/- 23 ms(-1) for skin. Velocity of the compound backfat
      decreased with overall thickness. Attenuation was not affected by thickness
      ranging between 1.6 +/- 0.7 and 2.7 +/- 1.5 dB MHz(-1)cm(-1) for all layers.
      Sound velocity was negatively correlated with fat content and dry matter. The
      obtained results are anticipated to improve signal correction prior to spectral
      analysis of ultrasound measurements at intact carcasses.

PMID- 21196088
TI  - Failure to sustain prepulse inhibition in adolescent marijuana users.
AB  - BACKGROUND: Marijuana use is typically initiated during adolescence, which is a
      critical period for neural development. Studies have reported reductions in
      prepulse inhibition (PPI) among adults who use marijuana chronically, although no
      human studies have been conducted during the critical adolescent period. METHODS:
      This study tested PPI of acoustic startle among adolescents who were either
      frequent marijuana users or naive to the drug (Controls). Adolescents were tested
      using two intensities of prepulses (70 and 85 dB) combined with a 105 dB startle
      stimulus, delivered across two testing blocks. RESULTS: There was a significant
      interaction of group by block for PPI; marijuana users experienced a greater
      decline in the PPI across the testing session than Controls. The change in PPI of
      response magnitude for users was predicted by change in urine THC/creatinine
      after at least 18 h of abstinence, the number of joints used during the previous
      week before testing, as well as self-reported DSM-IV symptoms of marijuana
      tolerance, and time spent using marijuana rather than participating in other
      activities. CONCLUSIONS: These outcomes suggest that adolescents who are frequent
      marijuana users have problems maintaining prepulse inhibition, possibly due to
      lower quality of information processing or sustained attention, both of may
      contribute to continued marijuana use as well as attrition from marijuana
      treatment.

PMID- 21196090
TI  - Influence of seminal plasma, spermatozoa and semen extender on cytokine
      expression in the porcine endometrium after insemination.
AB  - The effects of semen components or extender alone on the expression of selected
      cytokines [interleukine (IL)-1beta, IL-6, granulocyte-macrophage colony
      stimulating factor (GM-CSF), IL-10 and transforming growth factor (TGF)-beta1] on
      the porcine endometrium were studied, as well as the presence of
      polymorphonuclear neutrophilic granulocytes (PMNs). In experiment (Exp) I, groups
      of gilts were sampled at 5-6h after insemination with fresh semen in extender
      (Beltsville thawing solution, BTS), spermatozoa in extender (Spz), seminal plasma
      (SP), or only BTS (control). In Exp II, gilts were sampled 35-40h after
      insemination with Spz, SP, BTS or only catheter inserted (as control).
      Immunohistochemical (IHC) labelling of IL-6, IL-10 and TGF-beta1 was evident,
      especially in surface and glandular epithelia of the porcine endometrium. There
      were no consistent differences in IHC-labelling of the cytokines in relation to
      different treatments. However, the scores for IL-6 and IL-10 in surface
      epithelium and sub-epithelial connective tissue compartments were higher at 35
      40h than shortly (5-6h) after treatment. Cytoplasmic labelling in the sub
      epithelial connective tissue was observed in scattered individual cells but not
      in PMNs. Shortly (5-6h) after insemination, there were no differences between
      animals inseminated with BTS (control) and the semen components for any of the
      cytokine mRNAs. Later however, at 35-40h, lower endometrial expression of TGF
      beta1 mRNA was observed in the Spz and BTS groups compared with the control
      (catheter only). The same pattern was found for IL-10 (NS). The mRNA expression
      of IL-6 in the BTS inseminated group was higher compared to the control group.
      Insemination with SP resulted in significantly lower PMN cell infiltration in the
      sub-epithelial connective tissue compared with Spz or BTS groups shortly (5-6h)
      after insemination. Later (35-40h), a significant difference was found between SP
      (lower) and the control group (only catheter). To conclude, our results show that
      insemination and/or inseminated components modulated cytokine expression in the
      gilt endometrium. The semen extender BTS stimulated immune reactivity, as shown
      by down-regulation of the suppressive cytokine TGF-beta1. Insemination with
      solely SP clearly decreased PMN cell infiltration of the gilt endometrium.
      However, no clear relation between the cytokines studied and PMN cell presence
      was found.

PMID- 21196089
TI  - Oral administration of levo-tetrahydropalmatine attenuates reinstatement of
      extinguished cocaine seeking by cocaine, stress or drug-associated cues in rats.
AB  - Cocaine addiction is characterized by a persistently heightened susceptibility to
      drug relapse. For this reason, the identification of medications that prevent
      drug relapse is a critical goal of drug abuse research. Drug re-exposure, the
      onset of stressful life events, and exposure to cues previously associated with
      drug use have been identified as determinants of relapse in humans and have been
      found to reinstate extinguished cocaine seeking in rats. This study examined the
      effects of acute oral (gavage) administration of levo-tetrahydropalmatine (l
      THP), a tetrahydroprotoberberine isoquinoline with a pharmacological profile that
      includes antagonism of D1, D2 and D3 dopamine receptors, on the reinstatement of
      extinguished cocaine seeking by a cocaine challenge (10mg/kg, ip), a stressor
      (uncontrollable electric footshock [EFS]) or response-contingent exposure to a
      stimulus (tone and light complex) previously associated with drug delivery in
      male Sprague-Dawley rats. Extinguished drug seeking was reinstated by ip cocaine,
      EFS, or response-contingent presentation of drug-associated cues in vehicle
      pretreated rats following extinction of iv cocaine self-adminisration. Oral
      administration of either 3.0 or 10.0mg/kg l-THP 1h prior to reinstatement testing
      significantly attenuated reinstatement by each of the stimuli. Food-reinforced
      responding and baseline post-extinction responding were significantly attenuated
      at the 10.0, but not the 3.0mg/kg, l-THP dose, indicating that the effects of
      3mg/kg l-THP on reinstatement were likely independent of non-specific motor
      impairment. These findings further suggest that l-THP may have utility for the
      treatment of cocaine addiction.

PMID- 21196091
TI  - Evaluation of valproate effects on acylcarnitine in epileptic children by LC
      MS/MS.
AB  - BACKGROUND: Valproate (VPA) is a simple fatty acid and a substrate for the fatty
      acid beta-oxidation pathway. Previous data suggested that the toxicity of VPA may
      be provoked by carnitine deficiency and the inhibition of mitochondrial beta
      oxidation. OBJECTIVE: The aim of the present study was to elucidate the effect of
      VPA treatment on carnitine and isomer-differentiated acylcarnitine disposition,
      and determined the relationships between acylcarnitines and blood VPA levels in
      long-term treated patients with VPA and/or other antiepileptic drugs. METHODS:
      Serum samples were obtained from children aged 1-15 years old treated for at
      least 6 months with VPA alone (n=28) or VPA combined with other anticonvulsants
      (n=23) and untreated controls (n=23). Serum acylcarnitines were separated from
      their isomers and quantified using high-performance liquid chromatography-tandem
      mass spectrometry. RESULTS: We found higher 3-hydroxyisovalerylcarnitine levels
      and trace amounts of valproylcarnitine in both VPA monotherapy and polytherapy
      patients. Other acylcarnitines, hexanoylcarnitine, C12, C14:1-carnitines and the
      ratio of long-chain acylcarnitine to free carnitine were also higher in VPA
      polytherapy individuals than in controls. VPA monotherapy does not result in
      decreases in free carnitine or in the accumulation of long-chain acylcarnitines.
      Blood VPA concentrations correlated positively with hexanoylcarnitine, C12,
      C14:1, C16:1, C18:1-carnitines in all VPA-treated children (n=51). CONCLUSION:
      Long-term VPA treatment in pediatric patients could affect some specific
      acylcarnitines, which is enhanced by the concomitant use of other
      anticonvulsants, and the formation of valproylcarnitine alone seems insufficient
      to develop severe carnitine deficiency at therapeutic doses of VPA.

PMID- 21196092
TI  - Treatment of West syndrome.
AB  - West syndrome is one of the most refractory epileptic syndromes in infancy, and
      many researchers have made great effort to find optimal treatment modalities for
      this syndrome. In this review, previous literature on optimal treatments of West
      syndrome and its refractory nature were briefly presented, followed by an
      introduction of recent publication of expert opinions from the US and Europe. An
      Asian expert opinion generated by a short questionnaire survey was then
      presented. It was shown that medically proven optimal treatment of West syndrome
      is not always the practical treatment of choice in Asian countries. Cost and
      geographical regions should also be taken into account in making practical
      choices for treatment of West syndrome.

PMID- 21196093
TI  - Diagnostic image quality of a comprehensive high-pitch dual-spiral cardiothoracic
      CT protocol in patients with undifferentiated acute chest pain.
AB  - OBJECTIVE: To evaluate diagnostic image quality of high-pitch dual source
      comprehensive cardiothoracic CT protocol in patients presenting with acute
      undifferentiated chest pain. MATERIALS AND METHODS: Consecutive symptomatic
      subjects (n=51) with undifferentiated acute chest pain underwent ECG-synchronized
      high-pitch dual-spiral chest CT angiography (Definition Flash, Siemens Medical
      Solutions, 2 * 100 kVp or 2 * 120 kV if BMI>30, collimation: 128 * 0.6mm, pitch:
      3.2). Independent investigators determined the image quality of each cardiac and
      pulmonary vessel segment, measured contrast-to-noise-ratio (CNR), and determined
      radiation exposure. In addition, the prevalence of CT findings (pulmonary
      embolism (PE), aortic dissection (AD) and significant coronary stenosis (>= 50%))
      was determined. Univariate and multivariate analysis were performed to determine
      the subpopulation with highest diagnostic quality. RESULTS: Among 51 subjects
      (66% male, average age: 63 +/- 15.8), the prevalence of positive CT findings was
      moderate (overall: 11.7%). Overall, image quality of the pulmonary, aortic and
      coronary vasculature was good (1.26 +/- 0.43 and CNR: 2.52) with an average
      radiation dose of 3.82 mSv and 3.2% of segments rated non-evaluable. The image
      quality was lowest in the coronary arteries (p=0.02), depending on the heart rate
      (r=0.52, p<0.001). In subjects with a heart rate of <= 65 bpm (n=30) subjective
      image quality and CNR of the coronary arteries were higher (1.6 +/- 0.5 vs. 2.1
      +/- 0.5, p=0.03 and 1.21 +/- 0.3 vs. 1.02 +/- 0.3, p=0.05) with only 1.5%
      segments classified as non-evaluable. CONCLUSION: High-pitch dual-spiral
      comprehensive cardiothoracic CT provides low radiation exposure with excellent
      image quality at heart rates <= 65 bpm. In subjects with higher heart rates,
      image quality of the aortic and pulmonary vasculature remains excellent, while
      the assessment of the coronary arteries degrades substantially.

PMID- 21196094
TI  - Effective dose range for dental cone beam computed tomography scanners.
AB  - OBJECTIVE: To estimate the absorbed organ dose and effective dose for a wide
      range of cone beam computed tomography scanners, using different exposure
      protocols and geometries. MATERIALS AND METHODS: Two Alderson Radiation Therapy
      anthropomorphic phantoms were loaded with LiF detectors (TLD-100 and TLD-100 H)
      which were evenly distributed throughout the head and neck, covering all
      radiosensitive organs. Measurements were performed on 14 CBCT devices: 3D
      Accuitomo 170, Galileos Comfort, i-CAT Next Generation, Iluma Elite, Kodak 9000
      3D, Kodak 9500, NewTom VG, NewTom VGi, Pax-Uni3D, Picasso Trio, ProMax 3D,
      Scanora 3D, SkyView, Veraviewepocs 3D. Effective dose was calculated using the
      ICRP 103 (2007) tissue weighting factors. RESULTS: Effective dose ranged between
      19 and 368 MUSv. The largest contributions to the effective dose were from the
      remainder tissues (37%), salivary glands (24%), and thyroid gland (21%). For all
      organs, there was a wide range of measured values apparent, due to differences in
      exposure factors, diameter and height of the primary beam, and positioning of the
      beam relative to the radiosensitive organs. CONCLUSIONS: The effective dose for
      different CBCT devices showed a 20-fold range. The results show that a
      distinction is needed between small-, medium-, and large-field CBCT scanners and
      protocols, as they are applied to different indication groups, the dose received
      being strongly related to field size. Furthermore, the dose should always be
      considered relative to technical and diagnostic image quality, seeing that image
      quality requirements also differ for patient groups. The results from the current
      study indicate that the optimisation of dose should be performed by an
      appropriate selection of exposure parameters and field size, depending on the
      diagnostic requirements.

PMID- 21196095
TI  - Measuring providers' verbal and nonverbal emotion recognition ability:
      reliability and validity of the Patient Emotion Cue Test (PECT).
AB  - OBJECTIVE: To describe the development and validation of the Patient Emotion Cue
      Test (PECT) as a tool to measure providers' emotion cue recognition ability.
      METHODS: The PECT consists of 47 video clips depicting emotion cues that
      systematically vary in intensity of both verbal and nonverbal contents. The PECT
      assesses the provider's ability to detect and identify patients' emotion cues
      accurately. A multi-stage development process produced the PECT. Reliability and
      validity were assessed in three studies. RESULTS: Scores on the PECT are normally
      distributed with significantly above chance responding. Across three studies, the
      PECT demonstrates convergent validity through significant correlations with
      standardized tests representing multiple channels of emotion recognition,
      including the face, body, and voice. The PECT shows adequate inter-item and split
      half reliability. CONCLUSION: The PECT is an easily administered, reliable, and
      valid test of emotion cue recognition. PRACTICE IMPLICATIONS: The PECT can be
      used in future research on providers' emotion recognition ability, for evaluating
      self-assessment of ability, and as a teaching tool in medical schools.

PMID- 21196096
TI  - [Role of Helicobacter pylori infection in iron deficiency anemia].
AB  - Anemia induced by digestive diseases refers to anemia due to iron deficiency.
      Conventional gastrointestinal diagnostic workup fails to establish the cause of
      iron deficiency in about one third of patients. Abnormal iron absorption is
      increasingly recognized as an important cause of unexplained iron deficiency. The
      importance of coeliac disease as a possible cause of iron deficiency anemia
      refractory to oral iron treatment, without other manifestations of malabsorption
      syndrome, is increasingly being recognized. In addition, Helicobacter pylori (HP)
      has been implicated in several recent studies as a cause of iron deficiency
      anemia (IDA) refractory to oral iron treatment. Cure of previously refractory IDA
      by HP eradication provides strong evidence supporting a cause-and-effect
      relationship. In order to establish a cause-and-effect relationship between HP
      gastritis and IDA, prospective randomized studies comparing the effects of iron
      administration with or without H. pylorieradication are highly recommended.

PMID- 21196097
TI  - [Acute aortic syndromes: major advances, the result of effective
      multidisciplinary cooperation].

PMID- 21196098
TI  - The lung in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a common inflammatory disease, affecting about 1% of
      the population. Although a major portion of the disease burden including excess
      mortality is due to its extra-articular manifestations, the prevalence of RA
      associated lung disease is increasing. RA can affect the lung parenchyma,
      airways, and the pleura; and pulmonary complications are directly responsible for
      10 to 20% of all mortality. Even though pulmonary infection and drug toxicity are
      frequent complications of RA, lung disease directly associated with the
      underlying RA is more common. The prevalence of a particular complication varies
      based on the characteristics of the population studied, the definition of lung
      disease used, and the sensitivity of the clinical investigations employed. An
      overview of lung disease associated with RA is presented here with an emphasis on
      parenchymal lung disease, pleural effusion, and airway involvement.

PMID- 21196099
TI  - [High blood pressure in the emergency department: epidemiology and evaluation of
      a dedicated consultation].
AB  - OBJECTIVES: The Arterial High blood pressure represents a consultation on 5 in
      general medicine. The main objective of our study was to estimate patients'
      proportion appearing at emergency department (ED) with a high Blood pressure and
      to demonstrate that it is possible to detect the patients at risk of essential
      and secondary hypertension as well as their cardiovascular risk there. METHODS:
      Non-interventional forward-looking Study led over 6 weeks. After measure of the
      vital parameters in the reception of ED, the patients were included if the
      Systolic Blood Pressure (SBP) was >= 140 mmHg and?or Diastolic Blood Pressure
      (DBP) >= 90 mmHg. A control of Blood Pressure (BP) was made at least 40 minutes
      after the inclusion. If the Arterial High blood pressure persisted (BP >= 140/90
      mmHg and age < 30 years or BP >= 180/110 mmHg after 30 years), the patients had
      to see again a cardiologist of the hospital in 7 days because they were
      considered as at high cardiovascular risk. RESULTS: A high initial BP was
      discovered to 582 (8,7 %) 6685 patients having consulted in ED during the period
      of the study. 64 % of them (n = 372) had a persistent Arterial High Blood
      pressure after 40 minutes. 27 patients, defined at high cardiovascular risk had a
      proposition of consultation of cardiology, appeared 11 to it. 4 secondary
      hypertension was discovered. CONCLUSION: During the period of study, 582 patients
      presented a High BP. To 64 % of those who had a control of BP this imbalance was
      confirmed. The patients (n=27) presenting a high cardiovascular risk had a
      proposition of fast consultation. This one allowed discovering 4 secondary
      hypertension. There is thus a utility to estimate the BP in a systematic way at
      Emergency Department.

PMID- 21196100
TI  - Analysis of the rate of convergence of least squares neural network regression
      estimates in case of measurement errors.
AB  - Estimation of a regression function from data which consists of an independent
      and identically distributed sample of the underlying distribution with additional
      measurement errors in the independent variables is considered. It is allowed that
      the measurement errors are not independent and have a nonzero mean. It is shown
      that the rate of convergence of suitably defined least squares neural network
      estimates applied to this data is similar to the rate of convergence of least
      squares neural network estimates applied to an independent and identically
      distributed sample of the underlying distribution as long as the measurement
      errors are small.

PMID- 21196101
TI  - [Impact on parents of cerebral palsy in children: a literature review].
AB  - Cerebral palsy is the commonest cause of motor impairment in childhood. Parents
      of children with this particular neurodevelopmental disorder face many problems
      encountered by disabled children's parents. The aim of the present paper is to
      report the current knowledge on this parental impact, highlighting consensus and
      disagreement. A literature search was conducted using the key words "Cerebral
      palsy" and "Parents/Father/Mother" and "Adapt/Adjust/Cost/Economic/Impact/Well
      being" in the Medline and PsycInfo databases searching for articles published
      between 1989 and 2009. Seven parental impact dimensions were distinguished: time
      spent, occupational restrictions, social relationships, family relationships,
      psychological well-being, physical health, and financial burden. Of 40 selected
      references, the studies were mostly cross-sectional, although longitudinal
      surveys highlighted the causal relationship between factors. Despite various
      methodologies, this review confirms that parents of CP children have greater risk
      of experiencing a sense of burden than parents of typically normally developing
      children. Time spent caring for the child appears to be an important factor that
      depends on the child's autonomy. The 7 impact dimensions seem to be related to
      each other and to child's and caregiver's characteristics. The severity of motor
      impairment is not unanimously viewed as a worsening factor: however, the child's
      behavioral problems influence the impact experienced by the parents. The level of
      intellectual impairment also has a negative influence on family relationships and
      on the parent's psychological well-being. The child's developmental stage seems
      to be related to the level of parental impact, but there is no agreement on the
      dimensions involved. We also observed that the mother and father do not
      experience this situation in the same way, probably because of the role played by
      each one in the family. The current literature lacks data on caregiver
      characteristics, identifying families at risk of burden, and the environmental
      context that would allow for a less negative impact on parents. In addition, the
      tools measuring the impact lack standardization. No questionnaire covering all 7
      dimensions exists, but useful validated questionnaires for different dimensions
      were identified. We consider that the caregiver's occupation and physical health
      needs further research. The current knowledge is insufficient for proposing an
      overall model taking all the dimensions into account. Research is needed before a
      complete model of the CP child's impact on parents can be tested in view of
      providing guidelines to professionals for identifying families with a risk of
      maladaptation and suggesting solutions to decrease the negative impact.

PMID- 21196102
TI  - Carotid atherosclerosis and lipoprotein particle subclasses in familial
      hypercholesterolaemia and familial combined hyperlipidaemia.
AB  - BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) and familial combined
      hyperlipidaemia (FCH) are common atherogenic disorders with great variability in
      cardiovascular disease (CVD). No direct atherosclerosis burden comparisons have
      been performed between FH and FCH in relation to lipoprotein particle
      distribution. METHODS AND RESULTS: Risk factors and three measures of carotid
      intima-media thickness (IMT) in both sides were determined in 572 FH, 250 FCH and
      200 controls. Lipoproteins were assessed by nuclear magnetic resonance (NMR)
      spectroscopy. Compared with controls, IMT measures were increased in FH and FCH.
      FCH had the highest adjusted mean-maximum IMT. FH had twice low-density
      lipoprotein (LDL) particles than controls, but similar LDL subclass size and
      distribution. FCH subjects also had increased LDL particles and the highest
      number of small LDL (1519 +/- 731 nmol l(-1) vs. 887 +/- 784 nmol l(-1) in FH and
      545 +/- 409 nmol l(-1) in controls). Age, gender, cholesterol/high-density
      lipoprotein (HDL) ratio, smoking and systolic blood pressure were independently
      associated with IMT in FH (r(2) = 0.38). The same variables, except
      cholesterol/HDL ratio, were associated with IMT in FCH (r(2) = 0.40). Among NMR
      lipoproteins, only VLDL and chylomicrons increased IMT prediction in FCH by 0.8%.
      CONCLUSION: FH and FCH subjects show increased carotid atherosclerosis in
      relation to classical risk factors. Lipoprotein subclasses do not substantially
      contribute to IMT variability.

PMID- 21196103
TI  - The aggressive behavior of Nile tilapia introduced into novel environments with
      variation in enrichment.
AB  - Many studies show environmental enrichment is correlated with benefits to captive
      animals; however, one should not always assume this positive relationship given
      that enrichment increases the amount of resources that a territorial animal must
      defend and possibly affects its aggressive dynamics. In this study, we tested if
      environmental enrichment affects aggressive interactions in the aggressive fish
      Nile tilapia (Oreochromis niloticus). We compared fights staged between pairs of
      male tilapia of similar size (= matched in resource holding potential) in a novel
      arena that was either barren or enriched, to examine whether enrichment enhances
      territory value in line with theoretical predictions, with the potential for
      compromised welfare. We evaluated time elapsed until the first attack (latency),
      frequency of aggressive interactions and fight duration. We detected fight
      dynamic differences at the pair level. Higher resource value generated increased
      aggression but had no effect on fight duration or latency. This conclusion is in
      line with game theory predictions concerning resource value and contradicts the
      theory that enrichment of the environment will serve welfare purposes.

PMID- 21196104
TI  - Efficacy and safety of fluticasone and formoterol in a single pressurized metered
      dose inhaler.
AB  - BACKGROUND: Fluticasone and formoterol are well established medications for the
      treatment of asthma. This study (Clinicaltrials.gov identifier: NCT00734318)
      compares the efficacy and safety of a combination of these drugs in a single
      inhaler (fluticasone/formoterol) versus the individual components (fluticasone +
      formoterol). METHODS: Patients aged >= 18 years (n=620) with a history of severe,
      persistent reversible asthma for >= 6 months prior to screening were included in
      this randomized, double-blind study, which consisted of a screening phase of up
      to 5 days, a 2-week run-in phase and an 8-week treatment period. RESULTS:
      Fluticasone/formoterol (500/20 MUg, b.i.d.) was at least as effective as
      fluticasone + formoterol (500 MUg + 24 MUg, b.i.d.) with respect to the primary
      outcome measure: there were similar increases in mean pre-morning dose forced
      expiratory volume in the first second (FEV(1)) in these two groups.
      Fluticasone/formoterol (500/20 MUg, b.i.d.) also demonstrated similar efficacy to
      fluticasone + formoterol in terms of change in mean FEV(1) from baseline pre
      morning dose to 2 h post-morning dose at week 8, as well as for several secondary
      parameters. Fluticasone/formoterol (500/20 MUg, b.i.d.) demonstrated superiority
      to fluticasone monotherapy (500 MUg, b.i.d.) and fluticasone/formoterol (100/10
      MUg, b.i.d.) for several secondary efficacy parameters. Fluticasone/formoterol
      had a similar safety and tolerability profile to fluticasone + formoterol.
      CONCLUSION: This study demonstrated that the fluticasone/formoterol combination
      is at least as effective as its components administered concurrently from
      separate inhalers. Fluticasone/formoterol (500/20 MUg, b.i.d.) showed superior
      efficacy to its inhaled corticosteroid component alone and the efficacy of
      fluticasone/formoterol was dose-dependent for several clinically important
      parameters.

PMID- 21196105
TI  - Inhaled corticosteroids vs. leukotriene-receptor antagonists and asthma
      exacerbations in children.
AB  - BACKGROUND: Compared to inhaled corticosteroids (ICS), better use of leukotriene
      receptor antagonists (LTRA) may lead to a greater reduction in exacerbations
      among asthmatic children in real-life settings. METHODS: To test this hypothesis,
      we used the Quebec administrative databases and identified a cohort of 27,355
      asthmatic children aged 5-15 years in whom ICS or LTRA monotherapy was initiated
      in 1998-2005. The primary outcome was the rate of moderate-or-severe asthma
      exacerbations (emergency department visit or hospitalization for asthma or a
      dispensed prescription of oral corticosteroids) over the subsequent year. The
      adjusted rate ratios (RR) of asthma exacerbations were estimated with Poisson
      regression models. To minimize confounding by indication, all analyses were
      stratified by the presence or not of an asthma exacerbation in the year before
      treatment initiation. We also measured the proportion of days with supply
      prescribed and patient's adherence with the Proportion of Prescribed Days Covered
      (PPDC). RESULTS: The risk of exacerbations was significantly higher in the ICS
      than the LTRA group among children with no previous exacerbation (RR = 2.3; 95%
      CI:1.3-4.0), but not in those with >=1 exacerbations (RR = 1.6; 0.8-3.1). The
      PPDC was similar between the groups (66%) but the proportion of days with supply
      prescribed was significantly higher in the LTRA than the ICS group (52% vs. 34%),
      resulting in higher use. CONCLUSIONS: While confounding by indication cannot be
      firmly ruled out, ICS appears to be more frequently prescribed as an intermittent
      than a daily controller therapy resulting in less use, which may contribute to
      the apparent lower effectiveness compared to LTRA.

PMID- 21196106
TI  - Scaling methane oxidation: from laboratory incubation experiments to landfill
      cover field conditions.
AB  - Evaluating field-scale methane oxidation in landfill cover soils using numerical
      models is gaining interest in the solid waste industry as research has made it
      clear that methane oxidation in the field is a complex function of climatic
      conditions, soil type, cover design, and incoming flux of landfill gas from the
      waste mass. Numerical models can account for these parameters as they change with
      time and space under field conditions. In this study, we developed temperature,
      and water content correction factors for methane oxidation parameters. We also
      introduced a possible correction to account for the different soil structure
      under field conditions. These parameters were defined in laboratory incubation
      experiments performed on homogenized soil specimens and were used to predict the
      actual methane oxidation rates to be expected under field conditions. Water
      content and temperature corrections factors were obtained for the methane
      oxidation rate parameter to be used when modeling methane oxidation in the field.
      To predict in situ measured rates of methane with the model it was necessary to
      set the half saturation constant of methane and oxygen, K(m), to 5%,
      approximately five times larger than laboratory measured values. We hypothesize
      that this discrepancy reflects differences in soil structure between homogenized
      soil conditions in the lab and actual aggregated soil structure in the field.
      When all of these correction factors were re-introduced into the oxidation module
      of our model, it was able to reproduce surface emissions (as measured by static
      flux chambers) and percent oxidation (as measured by stable isotope techniques)
      within the range measured in the field.

PMID- 21196107
TI  - Quantum dot based immunosensor using 3D circular microchannels fabricated in
      PDMS.
AB  - Microchannel is basic functional component of microfluidic chip and every step
      forward of its construction technique has been receiving concern all over the
      world. The present work describes a novel, rapid and simple fabrication technique
      for building 3D microchannels in poly(dimethyl siloxane) (PDMS) elastomer. These
      microchannels were used for rapid detection of antigens (E. coli) by quantum dot
      (QD) based approach. Luminescent QD (CdTe) were synthesized by aqueous method and
      characterized using high resolution transmission electron microscopy (HRTEM),
      fluorescence spectroscopy and X-ray diffraction (XRD). The QDs were
      functionalized with anti-E. coli antibodies for immuno-detection. The reported
      process allowed easier and faster method of fabrication of circular 3D
      micochannels and demonstrated their potential use in an immuno-biosensor device.

PMID- 21196108
TI  - Highly-sensitive organophosphorous pesticide biosensors based on nanostructured
      films of acetylcholinesterase and CdTe quantum dots.
AB  - The optical transducer of CdTe semiconductor quantum dots (QDs) has been
      integrated with acetylcholinesterase enzyme (AChE) by the layer-by-layer (LbL)
      assembly technique, resulting in a highly sensitive biosensor for detection of
      organophosphorus pesticides (OPs) in vegetables and fruits based on enzyme
      inhibition mechanism. The detection limits of the proposed biosensors are as low
      as 1.05 * 10(-11) M for paraoxon and 4.47 * 10(-12) M for parathion, which are
      significantly better than those of the conventional GC/MS methods or amperometric
      biosensors (0.5 nM). These biosensors are used for quick determination of low
      concentrations of OPs in real vegetable and fruit samples and exhibit
      satisfactory reproducibility and accuracy. Moreover, the stock stability of the
      biosensors are very good due to the stabilizing environment for the enzyme in the
      nanostructures made by LbL technique. Many advantages provided by these
      biosensors, like fluorescent change recognized by naked eyes and mass production
      with low cost, will facilitate future development of rapid and high-throughput
      screening of OPs.

PMID- 21196109
TI  - Electrospun gold nanofiber electrodes for biosensors.
AB  - A new form of high surface area bioelectrode, based on nanofibers of electrospun
      gold with immobilized fructose dehydrogenase, was developed. The gold fibers were
      prepared by electroless deposition of gold nanoparticles on an electrospun
      poly(acrylonitrile)-HAuCl(4) fiber. The material was characterized using electron
      microscopy, XRD and BET, as well as cyclic voltammetry and biochemical assay of
      the immobilized enzyme. The electrochemical surface area of the gold microfibers
      was 0.32 +/- 0.04 m(2)/g. Fructose dehydrogenase was covalently coupled to the
      gold surface through glutaraldehyde crosslinks to a cystamine monolayer. The
      enzyme exhibited mediated electron transfer directly to the gold electrode and
      catalytic currents characteristic of fructose oxidation in the presence of a
      ferrocene methanol mediator were observed. The limit of detection of fructose was
      11.7 MUM and the K(M) of the immobilized enzyme was 5mM. The microfiber electrode
      was stable over 20 cycles with a 3.05% standard deviation. The response time of
      the sensor was less than 2.2s and reached half maximum value within 3.6s. The
      sensor was proven to be accurate and precise in both serum and popular beverages
      sweetened with high fructose corn syrup. The addition of glucose isomerase
      enabled the sensor to perform with glucose, thus expanding the available analyte
      selection for the sensor.

PMID- 21196110
TI  - High spatial resolution impedance measurement of EIS sensors for light
      addressable cell adhesion monitoring.
AB  - In this paper, impedance measurement of electrolyte-insulator-semiconductor (EIS)
      structure with high spatial resolution was proposed to monitor cell adhesion. The
      light addressing ability of this work overcomes the geometrical restrict of cell
      culture on conventional impedance detection devices such as interdigitated
      electrode (IDE) and electric cell-substrate impedance sensing (ECIS). Instead of
      studying cells on predetermined sites of IDE and ECIS, cells cultured anywhere on
      EIS sensor surface can be addressed and selected as target cells. Principle and
      primary models for high resolution impedance detection were described and tested
      by experiments. The EIS sensor was investigated in terms of its intrinsic
      characteristics, like impedance behavior, voltage characteristic, frequency
      dependency and photovoltaic effect. Optimized working condition was studied for
      cell experiments. Cell adhesion under treatment of 0.1% Triton X-100 was
      monitored using rat kidney cells as the source. Results showed good sensitivity
      (10% change of impedance) and resolution (40 MUm) for cell adhesion impedance
      detection and suggested this work should be suitable for monitoring cell
      impedance. Further improvements on sensitivity, spatial resolution were discussed
      as well as the further applications for single cell monitoring and cell adhesion
      imaging.

PMID- 21196111
TI  - Protein folding and binding: from biology to physics and back again.

PMID- 21196112
TI  - Management of cerebral metastasis: evidence-based approach for surgery,
      stereotactic radiosurgery and radiotherapy.
AB  - Brain metastases constitute a significant disease burden and have a major impact
      on morbidity and mortality. This review discusses the relative merits of open
      surgery, whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS),
      which have been used alone and in combination with varying degrees of success for
      the treatment of newly diagnosed brain metastasis. Treatment aims to provide
      disease control with a good quality of life, although prolonged survival may not
      always be achieved. Decision to treat is based on several prognostic factors
      including age, performance status and control of the primary cancer. The recently
      developed disease-specific graded prognostic assessment (DS-GPA) scales can aid
      in clinical decision making for individual patients. Whole brain radiotherapy
      remains the mainstay of treatment and provides effective palliation. Omission of
      WBRT results in worse local and distant control, though not survival. Local
      tumour control can be achieved by either resection of stereotactic radiosurgery
      (SRS). In long-term survivors WBRT may cause cognitive decline and SRS is being
      explored as an alternative method of disease control. Increasingly, quality of
      life and neuro-cognitive function are being used as end-points in clinical
      trials.

PMID- 21196113
TI  - miR-124a is frequently down-regulated in glioblastoma and is involved in
      migration and invasion.
AB  - Glioblastoma (GBM) represents a formidable clinical challenge for both patients
      and treating physicians. Due to better local treatments and prolonged patient
      survival, remote recurrences are increasingly observed, underpinning the
      importance of targeting tumour migration and attachment. Aberrant expression of
      microRNA (miRNA) is commonly associated with cancer and loss of miR-124a has
      previously been implicated to function as a tumour suppressor. The assessment of
      miR-124a in clinical specimens has been limited and a potential role in migration
      and invasion has been unexplored until now. We measured the expression levels of
      mature miR-124a in a retrospective series of 119 cases of histologically
      confirmed GBM and found its expression was markedly lower in over 80% of the GBM
      clinical specimens compared to normal brain tissue. The level of reduction in the
      clinical cohort varied significantly and patients with lower than the average miR
      124a expression levels displayed shorter survival times. Endogenous miR-124a
      expression and the protein expression of three of its targets; IQ motif
      containing GTPase activating protein 1 (IQGAP1), laminin gamma1 (LAMC1) and
      integrin beta1 (ITGB1) were significantly reciprocally associated in the majority
      of the clinical cases. We confirmed this association in our in vitro model.
      Functionally, the ectopic expression of mature miR-124a in a GBM cell line
      resulted in significant inhibition of migration and invasion, demonstrating a
      role for miR-124a in promoting tumour invasiveness. Our results suggest that miR
      124a may play a role in GBM migration, and that targeted delivery of miR-124a may
      be a novel inhibitor of GBM invasion.

PMID- 21196114
TI  - Microbial community dynamics in mesophilic anaerobic co-digestion of mixed waste.
AB  - This paper identifies key components of the microbial community involved in the
      mesophilic anaerobic co-digestion (AD) of mixed waste at Rayong Biogas Plant,
      Thailand. The AD process is separated into three stages: front end treatment
      (FET); feed holding tank and the main anaerobic digester. The study examines how
      the microbial community structure was affected by the different stages and found
      that seeding the waste at the beginning of the process (FET) resulted in
      community stability. Also, co-digestion of mixed waste supported different
      bacterial and methanogenic pathways. Typically, acetoclastic methanogenesis was
      the major pathway catalysed by Methanosaeta but hydrogenotrophs were also
      supported. Finally, the three-stage AD process means that hydrolysis and
      acidogenesis is initiated prior to entering the main digester which helps improve
      the bioconversion efficiency. This paper demonstrates that both resource
      availability (different waste streams) and environmental factors are key drivers
      of microbial community dynamics in mesophilic, anaerobic co-digestion.

PMID- 21196115
TI  - Removal of water-borne microorganisms in floating media filter-microfiltration
      system for water treatment.
AB  - Floating plastic media pre-filter (PP) in combination with microfiltration
      membrane (MF) was applied to the removal of water-borne microorganism from
      surface water. The system was operated with and without coagulant addition. Jar
      test results suggested that alum and polyaluminum chloride could effectively
      remove turbidity, fecal coliforms (FC) and algae at their optimum doses.
      Nevertheless, none of those coagulants could accomplish high coliphage (CP)
      removal. Microorganism removal in the system was increasing along with time in
      the PP unit operated at 5-m(3)/m(2)/h filtration rate but opposite trend was
      observed at higher filtration rates (10-15m(3)/m(2)/h). Different coagulant types
      and filtration rates employed in the PP unit also affected microorganism removal
      in MF unit. The operation of PP unit at a filtration rate of 15m(3)/m(2)/h and MF
      unit at a filtration rate of 0.6m(3)/m(2)/d could achieve satisfactory turbidity
      and overall microorganism removal.

PMID- 21196116
TI  - Acclimation and activity of ammonia-oxidizing bacteria with respect to variations
      in zinc concentration, temperature, and microbial population.
AB  - Activity of ammonia-oxidizing bacteria (AOB) to simultaneous variation in Zn(2+)
      concentration (0.01-3.5mg/L), temperature (23-33 degrees C), and AOB
      concentration (3-30 * 10(6)gene copies/mL) in a steel industry wastewater
      treatment plant was evaluated. Two equations were developed to describe the lag
      period (i.e., AOB acclimation) and ammonia oxidation rate (i.e., growth of the
      AOB) depending on the variables. AOB concentration and temperature both had
      significant effects on lag period and the ammonia oxidation rate. Zn(2+)
      concentration only had a significant effect on ammonia oxidation rate at 5% alpha
      level. There was a significant interaction between AOB concentration and
      temperature for both lag period and ammonia oxidation rate. The effects of the
      variables were not significant when AOB concentration was higher than 2.0 *
      10(7)copies/mL. There was no visible shift or changes in AOB communities based on
      DGGE analysis with amoA gene primers.

PMID- 21196119
TI  - Transient restoration of succinate dehydrogenase activity after rhabdomyolysis in
      iron-sulphur cluster deficiency myopathy.
AB  - Myopathy with exercise intolerance and deficiency of iron-sulphur cluster
      proteins is caused by an intronic IVS5+382 G>C mutation in ISCU, the gene
      encoding the iron-sulphur cluster assembly protein (IscU). The mutation causes
      alternative splicing resulting in a truncated protein and severely reduced levels
      of IscU protein in muscle tissue. Disease manifestations include muscle
      fatigability, dyspnoea, cardiac palpitations and episodic myoglobinuria. Muscle
      tissue of these patients demonstrates marked histochemical succinate
      dehydrogenase deficiency and accumulation of iron in muscle fibres, which are
      morphological hallmarks of the disease. A biopsy specimen from a patient, two
      months after a severe attack of rhabdomyolysis, revealed regenerating muscle with
      normal succinate dehydrogenase activity and only minor iron accumulation, whereas
      another biopsy obtained nine years after the episode showed the typical hallmarks
      of the disease. The apparent explanation for the normal succinate dehydrogenase
      activity during regeneration was a markedly increased level of IscU protein in
      regenerating muscle tissue and an increase in normally spliced ISCU transcripts
      in the patient. The results have implications for diagnosis of the disease based
      on muscle biopsy findings and support the concept that an increase of normally
      spliced ISCU by RNA modulating therapy may be a therapeutic possibility for these
      patients.

PMID- 21196117
TI  - Enhancing denitrification using a carbon supplement generated from the wet
      oxidation of waste activated sludge.
AB  - This study compared the effect of four pure carbon supplements on biological
      denitrification to a liquor derived as a by-product from the wet oxidation (WO)
      of waste activated sludge. Sequencing batch reactors were used to acclimate
      sludge biomass, which was used in batch assays. Acetate, WO liquor and ethanol
      supplementation generated the fastest denitrification rates. Acetate and WO
      liquor were efficiently utilised by all acclimated biomass types, while poor
      rates were achieved with methanol and formate. When comparing an inoculum from an
      ethanol-supplemented and non-supplemented wastewater treatment plant (WWTP), the
      ethanol-acclimated sludge obtained superior denitrification rates when
      supplemented with ethanol. Similarly high nitrate removal rates were achieved
      with both sludge types with acetate and WO liquor supplementation, indicating
      that WO liquors could achieve excellent rates of nitrate removal. The performance
      of the WO liquor was attributed to the variety of organic carbon substrates
      (particularly acetic acid) present within the liquor.

PMID- 21196120
TI  - Upper limb kinematics: development and reliability of a clinical protocol for
      children.
AB  - This study proposed a child-friendly measurement procedure for the three
      dimensional analysis of upper limb movements, based on a comprehensive movement
      protocol. Within and between session reliability was tested in a group of 10
      typically developing children (TDC) (mean age 10.3+/-3.2 years). The movement
      protocol was constructed for children with hemiplegic cerebral palsy (HCP) and
      contained three reach tasks (forwards, upwards, sideways), three reach-to-grasp
      tasks (with objects requiring different hand orientations) and three gross motor
      tasks. Upper limb kinematics were calculated following the ISB-guidelines.
      Reliability of movement duration/speed and endpoint joint angles was assessed
      with the intraclass correlation coefficient; similarity of the waveforms with the
      coefficient of multiple correlation; measurement errors were also calculated.
      Reliability coefficients were generally high for movement duration/speed and most
      kinematic parameters. Endpoint angles for scapular tilting, shoulder elevation
      plane and elevation, elbow flexion-extension and wrist ulnar-radial deviation
      showed highest reliability. Angular waveforms were best repeated for scapular
      medio-lateral rotation and pro-retraction, shoulder elevation plane and
      elevation, and elbow flexion-extension. Results also seemed task-dependent. This
      study indicated that the proposed procedure could be used reliably to quantify
      upper limb movements in TDC. However, to compose proper age-related standards for
      the different tasks, larger study samples are needed. This will also help with a
      well-founded task-selection depending on the joints of interest. Finally, further
      research will need to establish the reliability in children with HCP.

PMID- 21196121
TI  - A meta-analysis of randomised controlled trials comparing the clinical and
      radiological outcomes following minimally invasive to conventional exposure for
      total knee arthroplasty.
AB  - Proponents of minimally invasive total knee arthroplasty (TKA) state accelerated
      patient recovery and increased patient satisfaction as advantages. However,
      retractors state a greater incidence of iatrogenic nerve injury, implant mal
      positioning and increased rates of revision. This study compares the clinical and
      radiological outcomes of minimally invasive and conventional exposure TKA using a
      meta-analysis. A search of published and unpublished literature was performed.
      Eighteen studies including 1582 TKAs were reviewed: 822 minimally invasive versus
      760 conventional exposure TKAs. The findings of this study suggest that whilst
      incision length was significantly smaller in MIS (p=0.001), and flexion range of
      motion was significantly greater following MIS (p=0.01), there was no
      statistically significant differences in all other clinical or radiological
      outcomes between MIS or conventional approach TKA surgery (p>0.05).

PMID- 21196122
TI  - High sensitivity biosensor measurement based on synchronous detection.
AB  - The principle of synchronous detection (SD) has been applied to biosensor
      measurement. SD principle achieves significant increases in the signal to noise
      ratio, limit of detection and overall measurement robustness. Application of SD
      in biosensor measurement improves the analysis of the response and avoids the
      influence of interference/noise produced by stirring, electromagnetic effects and
      influence of parasitic currents. SD also enables the decomposition of signal to
      stimulation response and phenomena with long time of response. Second-order
      phenomena are identifiable in the signal. Linear statistical model was used to
      develop software for identification of the stimulation signal in the output
      current. SD was applied to the response signal of a Photosystem II complex (PSII)
      biosensor. PSII response to light stimulation follows first order kinetics. The
      inhibition kinetics of PSII has been studied. Kinetic constants of herbicide
      binding to PSII depend linearly on herbicide concentration and enable measurement
      of its concentration at low concentrations (linear range for diuron is 10-6 to 10
      4 mM).

PMID- 21196124
TI  - HIV infection and contraception.
AB  - HIV infection primarily affects women of childbearing age worldwide, in both
      developed and developing countries. With the advent of effective antiretroviral
      treatment, women are living longer and healthier lives, and the opportunity to
      have a child with minimal fear of vertical transmission is now a reality. For HIV
      infected women, contraception and reproductive planning have become essential.
      Limited information is available on the variety of contraceptive options for HIV
      infected women. It is important for all health care practitioners to educate
      themselves on contraceptive options so that they can provide optimal reproductive
      care to their HIV-infected female patients.

PMID- 21196123
TI  - Negative regulation by nuclear receptors: a plethora of mechanisms.
AB  - Nuclear receptors are arguably the best understood transcriptional regulators. We
      know a great deal about the mechanisms through which they activate transcription
      in response to ligand binding and about the mechanisms through which they repress
      transcription in the absence of ligand. However, endocrine regulation often
      requires that ligand-bound receptors repress transcription of a subset of genes.
      An understanding of the mechanism for ligand-induced repression and how this
      differs from activation has proven elusive. A number of recent studies have
      directly or indirectly addressed this problem. Yet it seems the more evidence
      that accumulates, the more complex the mystery becomes.

PMID- 21196125
TI  - Long-term outcome of vagus nerve stimulation therapy after failed epilepsy
      surgery.
AB  - OBJECTIVE: Adequate control of intractable epilepsy continues to be a challenge.
      Little is known about the role of VNS therapy in intractable epilepsy in patients
      who failed to respond to surgical management. The objective of the present study
      is to determine the efficacy of vagus nerve stimulation therapy in patients with
      intractable epilepsy who have failed surgical and medical therapy. METHODS: All
      the patients who had persistent seizures after cranial surgery who subsequently
      underwent vagus nerve stimulator (VNS) placement at our institution from 1998 to
      2008 were included in the study. Thirty-seven consecutive patients were enrolled
      and followed for the outcome measures of seizure burden, anti-epileptic drug
      (AED) burden and quality of life (QoL). Minimum follow-up was 18 months. RESULTS:
      Overall, 24 (64.9%), 9 (24.3%), 4 (10.8%) patients reported less than 30%,
      between 30% and 60% and greater than 60% reduction in seizure frequency after VNS
      placement, respectively at a mean of 5 years follow-up period. Post-VNS anti
      epileptic requirement exhibited a decreasing trend. 17 patients (45.9%) report an
      improvement in QoL (better or much better). CONCLUSION: VNS therapy in patients
      who have failed medical and surgical therapies only provides marginal improvement
      in seizure control but has greater likelihood to improve subjective QoL issues.
      In addition, VNS has the potential to reduce AED burden without adversely
      impacting seizure management. Given the low surgical risk of VNS placement, vagus
      nerve stimulation as a therapeutic modality should be individualized to achieve
      best clinical response and fewest side effects.

PMID- 21196126
TI  - Urgent carotid endarterectomy in patients with recent/crescendo transient
      ischaemic attacks or acute stroke.
AB  - OBJECTIVES: Objective of this study was to review the results of urgent carotid
      endarterectomy (CEA) performed in patients with recent (< 24 h) or crescendo (at
      least 2 episodes in 24 h) transient ischaemic attack (TIA) or with acute stroke
      in a single centre experience. MATERIALS AND METHODS: From January 2000 to
      December 2008, 75 patients underwent urgent CEA for severe internal carotid
      artery stenosis and recent/crescendo TIA (51 patients, TIA group) or acute stroke
      (24 patients, stroke group). In patients with acute stroke the intervention was
      proposed on the basis of clinical and instrumental features (patient conscious,
      patency of middle cerebral artery, no lesions or limited brain infarction at CT
      scan) according to neurologists' suggestion. Data from all the interventions were
      prospectively collected in a dedicated database, which included main pre-, intra-
      and postoperative parameters. Independent neurological assessment with National
      Institute of Health Stroke Scale (NIHSS) score calculation was performed before
      the operation and within the 30th postoperative day. Early (< 30 days) results
      were evaluated in terms of mortality, modifications in NIHSS values and stroke
      and death rates. The surveillance program consisted of clinical and
      ultrasonographic examinations at 1, 6 and 12 months and yearly thereafter. Follow
      up results (survival, occurrence of ipsilateral stroke in TIA group, recurrence
      of stroke in stroke group) were analysed by Kaplan-Meier curves. RESULTS: Among
      patients presenting with TIA, 28 had crescendo TIAs and 23 had a recent TIA; In
      stroke group, two patients had a stroke in evolution, eight patients had a recent
      major non-disabling stroke and 14 patients had a recent minor stroke.
      Preoperative mean value of NIHSS score in stroke group was 4.7 (SD 3.2). There
      were 2 perioperative (< 30 days) deaths, both in stroke group, in one case due to
      acute respiratory failure and to fatal stroke in the other one (preoperative
      NIHSS value 9, postoperative 17), with a cumulative 30-day mortality rate of
      2.7%, significantly higher in stroke group (8.3%) than in TIA group (no death, p
      = 0.03). No postoperative cerebral haemorrhage occurred. In TIA group one
      postoperative major stroke occurred, with a 30-day stroke and death rate of 1.9%.
      In surviving patients of stroke group NIHSS value improved in 13 cases, with a
      mean improvement of 2 points (SD 0.9); in 8 cases the value remained unchanged,
      while in the remaining case it increased from 2 to 4. Mean postoperative NIHSS
      score in stroke group was 3.9 (SD 3.7), significantly reduced in comparison with
      preoperative value (p < 0.001). Mean duration of follow-up was 34 months (SD
      28.1). No ipsilateral stroke in patients of TIA group occurred; in stroke group a
      recurrent fatal stroke at 1 postoperative month was recorded. Estimated 48-month
      stroke-free survival rate TIA group was 95% and 79% in stroke group (p = 0.02).
      CONCLUSIONS: Urgent CEA in patients with recent/crescendo TIA provided in our
      experience excellent results, with low rates of perioperative and late stroke. In
      selected patients with acute stroke early surgery seems to provide acceptable
      results.

PMID- 21196127
TI  - The modulation of pain by attention and emotion: a dissociation of perceptual and
      spinal nociceptive processes.
AB  - Emotions and attention have been shown to influence the perception of pain and
      several psychophysiological studies have suggested an implication of descending
      modulatory mechanisms to explain these effects. However, the specificity of the
      neurophysiological mechanisms underlying the emotional and attentional modulation
      of pain still remains unclear. In order to differentiate the supra-spinal and
      spinal mechanisms involved in emotional and attentional modulation of pain, we
      measured pain perception (self-ratings) and the RIII reflex in healthy volunteers
      during the presentation of pleasant, unpleasant and neutral pictures, as well as
      during a baseline condition with no visual distractor (Experiment 1). In a second
      experiment, we manipulated the emotional arousal induced by pleasant and
      unpleasant pictures in order to compare more directly the effects of distraction
      and arousal. Whereas emotional valence influenced pain and the amplitude of the
      RIII reflex in the same direction (negative > positive), distraction by neutral
      pictures reduced pain but increased the RIII reflex relative to baseline.
      Increased arousal further potentiated the effects of negative valence on both
      pain and the RIII reflex and the effects of positive emotions on pain, as
      previously reported. However, arousal did not potentiate the inhibitory effect of
      positive pictures on the RIII and seems insufficient to account for the effect of
      distraction on the RIII. Overall, these data provide further evidence that
      attention and emotion modulate pain through partially dissociable
      neurophysiological mechanisms.

PMID- 21196128
TI  - Factors predicting patient satisfaction 2 years after total knee arthroplasty for
      osteoarthritis.
AB  - OBJECTIVE: To identify factors predicting patient satisfaction 2 years after
      total knee arthroplasty (TKA) for osteoarthritis. METHODS: Prospective
      multicenter study of patients followed up for 2 years after TKA for
      osteoarthritis. We evaluated pain and function (Lequesne index and WOMAC) at
      baseline and after 2 years. After 2 years, the patients rated their satisfaction
      as a percentage, with values greater than 50% defining good satisfaction. Factors
      associated with good satisfaction were identified by univariate analyses followed
      by multivariate analysis. RESULTS: Of 299 patients, 264 completed the study (26
      were lost to follow-up, six died, and three refused the 2-year evaluation),
      including 237 (89.8%) with satisfaction scores greater than 50%. Highly
      significant improvements were found after 2 years versus baseline in the Lequesne
      index (7.9 vs. 14.5, P<0.0001) and WOMAC index (26.3 vs. 51.3, P<0.0001). There
      were 26 (9.8%) complications. Factors significantly associated with good
      satisfaction in the multivariate model were absence of complications (P=0.004),
      body mass index less than 27 kg/m2 (P=0.015), high radiological joint narrowing
      score (P=0.038), age greater or equal to 70 years (P=0.038), and absence of
      depression at the 2-year evaluation (P=0.002). CONCLUSION: We report the first
      prospective multicenter study done in France to assess pain and function in a
      large number of patients treated with TKA for osteoarthritis. Our results
      indicate a high success rate. We identified three factors that predict patient
      satisfaction and can be assessed before surgery (age greater than 70 years,
      absence of obesity, and severe joint space narrowing).

PMID- 21196129
TI  - Obesity in primary antiphospholipid syndrome is associated with worse outcome.

PMID- 21196130
TI  - Rituximab in rheumatoid arthritis and the risk of malignancies: report from a
      French cohort.
AB  - OBJECTIVE: To determine in real-life conditions the safety of treatment with
      rituximab (RTX) in patients with rheumatoid arthritis (RA) regarding
      malignancies. METHODS: Analysis of safety data from a cohort of RA patients who
      received at least one course of RTX. RA patients with previous malignancies were
      followed-up and compared to the group of patients with no history of malignancy.
      RESULTS: One hundred and eighty-six RA patients, 33 (17.7%) males, the mean age
      and disease duration were 55.8 +/- 13.0 and 14.5 +/- 11.1 years, respectively.
      The mean follow-up was 22.3 +/- 15.1 months, corresponding to a follow-up of 346
      pt-years of RTX exposure. Among these, 24 (12.9%) patients had a history of a
      prior malignancy. Five cancers were diagnosed during follow-up with four new
      malignancies (1 prostate, 1 breast, 1 colon and 1 cervical cancers) and one
      recurrence of a known breast cancer. The overall cancer rate was 1.45/100 pt
      years (95%CI: 0.19 to 2.70), which is comparable to previously studied DMARD
      treated cohorts. No new hematopoietic neoplasms were reported and the six
      lymphomas that have been in remission prior to RTX-therapy remained under follow
      up. The baseline demographic and disease characteristics and the cancer-risk of
      the 24 patients who presented with a prior malignancy were similar to those with
      no cancer history (162 patients). CONCLUSIONS: Although based on a modest number
      of observed cancers, and despite selection bias (12.9% of prior malignancies in
      our RTX treated RA), this observational study suggests that RTX does not increase
      the cancer risk in RA patients.

PMID- 21196131
TI  - The central nervous system and inflammation in hypertension.
AB  - In recent years a major research effort has focused on the role of inflammation,
      and in particular adaptive immunity, in the genesis of hypertension. Hypertension
      stimulates the accumulation of inflammatory cells including macrophages and T
      lymphocytes in peripheral tissues important in blood pressure control, such as
      the kidney and vasculature. Angiotensin II modulates blood pressure via actions
      on the central nervous system (CNS) and the adaptive immune system. Recent work
      suggests that the central actions of angiotensin II via the circumventricular
      organs lead to activation of circulating T-cells and vascular inflammation. The
      neuro-immune system plays an essential role in the pathogenesis of hypertension
      and further understanding of this relationship could lead to the development of
      new treatment strategies.

PMID- 21196132
TI  - Impact of phase transition on the mouse oocyte spindle during vitrification.
AB  - During vitrification, the glass-like solidification is the phase-transition
      process from liquid to solid. Phase transition is one of the major factors
      suspected to affect the physiology of the oocyte, such as the structure of the
      meiotic spindle. Therefore, it is very important to investigate the systematic
      and morphological alterations of the metaphase-II spindle and chromosome
      arrangement during complete course of a vitrification and warming process. B6D2F1
      (C57BL/6 X DBA/2) mouse oocytes were cryopreserved by minimum volume cooling
      (MVC) method of vitrification in a solution with 15% ethylene glycol, 15%
      dimethylsulphoxide and 0.5 mol/l sucrose. To examine the spindle, oocytes were
      fixed before, during and after vitrification and were analysed by
      immunocytochemistry and confocal microscopy. It was shown that spindles in all
      oocytes could be maintained through the vitrification and warming process, even
      though they were exposed to extreme temperature and two rounds of phase
      transition. According to the sequential observations, chromosome alignment was
      maintained throughout the complete course of vitrification, warming and post
      warming stage. The impact of phase transition was barely detectable when the
      oocyte was exposed to the vitrification and warming process. The oocyte spindle
      was able to recover immediately after warming.

PMID- 21196133
TI  - Ooplast-mediated developmental rescue of bovine oocytes exposed to ethidium
      bromide.
AB  - Ooplasm transfer has been used successfully to treat infertility in women with
      ooplasmic insufficiency and has culminated in the birth of healthy babies. To
      investigate whether mitochondrial dysfunction is a factor in ooplasmic
      insufficiency, bovine oocytes were exposed to ethidium bromide, an inhibitor of
      mitochondrial DNA replication and transcription, during in-vitro maturation
      (IVM). Exposure of immature oocytes to ethidium bromide for 24h during IVM
      hampered meiotic resumption and the migration of cortical granules. However, a
      briefer treatment with ethidium bromide during the last 4h of IVM led to partial
      arrest of preimplantation development without affecting oocyte maturation.
      Ooplasm transfer was then performed to rescue the oocytes with impaired
      development. In spite of this developmental hindrance, transfer of normal ooplasm
      into ethidium bromide-treated oocytes resulted in a complete rescue of embryonic
      development and the birth of heteroplasmic calves. Although this study unable to
      determine whether developmental rescue occurred exclusively through introduction
      of unaffected mitochondria into ethidium bromide-damaged oocytes, e.g. ethidium
      bromide may also affect other ooplasm components, these results clearly
      demonstrate that ooplasm transfer can completely rescue developmentally
      compromised oocytes, supporting the potential use of ooplasm transfer in
      therapeutic applications.

PMID- 21196134
TI  - Determination of brain cytochrome P450 2E1 activity in rat with the probe of
      chlorzoxazone by liquid chromatography-mass spectrometry.
AB  - A simple and sensitive method was developed for the determination of cytochrome
      P450 2E1 (CYP2E1) activity based on the liquid chromatography-mass spectrometry
      (LC-MS) analysis of 6-hydroxychlorzoxazone generated by 6-hydroxylation of
      chlorzoxazone under specific catalysis of CYP2E1. In the proposed method, 2
      benzoxazolinone was chosen as internal standard and isopropyl ether was used as
      extraction solvent for sample preparation. The inter-day and intra-day precisions
      at low, medium and high concentrations of 6-hydroxychlorzoxazone were below
      20.0%, and the LOD (S/N=3) was 0.05 ng/mL. This method was applied to analyze the
      CYP2E1 activity of rat in different brain regions including frontal cortex (FC),
      cerebellum (CB), brain stem (BS), hippocampus (HC), striatum (ST), thalamus (TH),
      and olfactory bulb (OB). The results confirmed that chlorzoxazone was a suitable
      probe for the determination of CYP2E1 activity in brain regions and samples with
      low content of CYP2E1.

PMID- 21196135
TI  - Do body weight and gender shape the work force? The case of Iceland.
AB  - Most studies of the relationship between body weight - as well as its corollary,
      beauty - and labor-market outcomes have indicated that it is a function of a
      gender bias, the negative relationship between excess weight or obesity and labor
      market outcomes being greater for women than for men. Iceland offers an
      exceptional opportunity to examine this hypothesis, given that it scores
      relatively well on an index of gender equality comprising economic, political,
      educational, labor-market, and health-based criteria. Equipped with an advanced
      level of educational attainment, on average, women are well represented in
      Iceland's labor force. When it comes to women's presence in the political sphere,
      Iceland is out of the ordinary as well; that Icelanders were the first in the
      world to elect a woman to be president may suggest a relatively gender-blind
      assessment in the labor market. In the current study, survey data collected by
      Gallup Iceland in 2002 are used to examine the relationship between weight and
      employment within this political and social setting. Point estimates indicate
      that, despite apparently lesser gender discrimination in Iceland than elsewhere,
      the bias against excess weight and obesity remains gender-based, showing a
      slightly negative relationship between weight and the employment rate of women,
      whereas a slightly positive relationship was found for men.

PMID- 21196136
TI  - Recurrent cranial fibroblastic neoplasm in a male adolescent: case report and
      review of the literature.
AB  - Paediatric fibroblastic tumours are rare neoplasms, of which cranial fasciitis is
      the most common. We present a case of a male 7-year-old suffering from a cranial
      tumour preceded by a mild trauma. The tumour recurred despite radical resection
      within 8 months. Histologically, neither tumour could be classified as any
      published pathological entity. Both lesions were described as cellular
      fibroblastic neoplasms; in addition, the recurrent tumour featured a prominent
      myxoid matrix. In the 12 months following resection of the second tumour, no
      further disease recurrence has occurred.

PMID- 21196137
TI  - Oncological screening for Bilateral Breast Reduction: a survey of practice
      variations in UK Breast and Plastics surgeons 2009.
AB  - INTRODUCTION: Bilateral Breast Reduction (BBR) is a common procedure performed by
      Breast and Plastic surgeons in the UK. No consensus exists regarding preoperative
      screening for malignancy or for selective criteria for such screening.
      Preoperative BBR screening practices among UK Breast and Plastic surgeons are
      unknown. AIMS: Ascertain the preoperative and postoperative BBR screening
      practices of UK Breast and Plastic surgeons. MATERIALS AND METHODS: A
      questionnaire was posted to all 434 Breast and 335 Plastic surgeons in the UK.
      All results were analysed with relevant statistical methods. KEY RESULTS: 64% of
      Breast surgeons and 72% of Plastic surgeons responded. 40% of Breast surgeons and
      91% of Plastic surgeons perform BBR. Routine radiological screening: 92% Breast
      41% Plastic (p < 0.05). Routine breast examination prior to BBR: 98% Breast 91%
      Plastic. Routine histology for BBR specimens: 96% Breast 90% Plastic. Selective
      screening of patients aged 30-40 years old: Breast 38% Plastic 10%. Selective
      screening of patients aged 40-50: Breast 78%, Plastic 53%. Selective screening of
      patients with strong family history of breast cancer: Breast 72%, Plastic 91%.
      Selective screening of patients with previous breast cancer: Breast 77%, Plastic
      93%. CONCLUSIONS: There are significant differences in practice between UK Breast
      surgeons and Plastic surgeons in preoperative oncological screening for BBR. The
      large discrepancy in preoperative radiological screening, reflects a ubiquitous
      pro-screening ideology among Breast surgeons not prevalent among Plastic
      surgeons. These results will provoke debate towards the direction of consensus to
      ultimately reflect best practice.

PMID- 21196138
TI  - DNA methylation-based forensic tissue identification.
AB  - Identifying the source tissue of biological material found at crime scenes can be
      very informative in a number of cases. Despite their usefulness, current visual,
      catalytic, enzymatic, and immunologic tests for presumptive and confirmatory
      tissue identification are applicable only to a subset of samples, might suffer
      limitations such as low specificity, lack of sensitivity, and are substantially
      impacted by environmental insults. Moreover these assays are incompatible and
      thus cannot be multiplexed. Thus they are less amenable to automation. In
      addition their results are operator-dependent. A better alternative approach is
      tissue identification based on messenger RNA (mRNA) or microRNA (miRNA); however,
      RNA is not as stable as DNA, and requires the use of non-standard procedures by
      forensic laboratories. Herein a DNA-based assay is described that enables tissue
      identification based on detection of tissue-specific methylation patterns. DNA
      samples are subjected to digestion by a methylation-sensitive restriction
      endonuclease followed by multiplex amplification of specific genomic targets with
      fluorescent-labeled primers, capillary electrophoresis of amplification products,
      and automatic signal analysis by dedicated software, yielding the source tissue
      of the sample. The single tube assay was designed for easy integration by
      forensic laboratories (as the assay utilizes the same platforms as current
      forensic STR profiling). The system is fully automatable, provides operator
      independent results, and allows combining tissue identification with profiling in
      a single procedure. The assay was tested on 50 DNA samples from blood, saliva,
      semen, and skin epidermis, and the source tissue was successfully identified in
      all cases. Detection of semen and DNA profiling were combined into one assay and
      the ability to detect mixtures of semen and saliva in various ratios was
      demonstrated. The assay correctly detected semen in all samples where it was
      present, and the calculated percentage of semen was comparable to the fraction of
      semen in the samples. The results demonstrate that methylation-based tissue
      identification is more than a proof-of-concept. The methodology holds promise as
      another viable forensic DNA analysis tool for characterization of biological
      materials.

PMID- 21196139
TI  - Scented products emit a bouquet of VOCs.

PMID- 21196140
TI  - Integrated urban-rural frameworks for air pollution and health-related research
      in India: the way forward.

PMID- 21196141
TI  - Separating people from pollution: individual and community interventions to
      mitigate health effects of air pollutants.

PMID- 21196142
TI  - School siting: EPA says location matters.

PMID- 21196143
TI  - Vehicle motion alarms: necessity, noise pollution, or both?

PMID- 21196144
TI  - Estrogens from the outside in: alkylphenols, BPA disrupt ERK signaling in vitro.

PMID- 21196146
TI  - Examining nanotech's clean energy promises.

PMID- 21196147
TI  - Tobacco bio-oil kills agricultural pests.

PMID- 21196148
TI  - A measure of community exposure: PFOA in well water correlates with serum levels.

PMID- 21196149
TI  - Lead doesn't spare the rod: low-level exposure supercharges retinal cell
      production in mice.

PMID- 21196152
TI  - Out of equilibrium? The world's changing ice cover.

PMID- 21196154
TI  - Is insulin resistance a disorder of the brain?
AB  - There is reasonable evidence to suggest that insulin resistance may have its
      origins in the hypothalamus. Insulin secretion is regulated by sympathetic and
      parasympathetic nervous systems and modulates the concentrations of hypothalamic
      neuropeptides and monoaminergic neurotransmitters, and, in return, hypothalamic
      monoamines regulate the secretion of insulin by pancreatic beta cells. A lesion
      of the ventromedial hypothalamus produces all the features of the metabolic
      syndrome including insulin resistance and hyperinsulinemia. These and other
      evidence suggest that insulin resistance may very well be a disease of the brain.

PMID- 21196155
TI  - L-arginine, NO and asymmetrical dimethylarginine in hypertension and type 2
      diabetes.
AB  - Both hypertension and type 2 diabetes mellitus are common and there are no
      reliable markers either to predict their development or complications. High fat
      diet and carbohydrate-rich diet enhance serum asymmetrical dimethylarginine
      (ADMA) levels, an endogenous inhibitor of nitric oxide synthesis. ADMA levels are
      elevated in patients with hypertension, poor control of hyperglycemia, diabetic
      microangiopathy and macroangiopathy and dyslipidemia. One of the earliest signs
      of vascular dysfunction and insulin resistance, which are present in hypertension
      and type 2 diabetes mellitus, is an elevation in serum ADMA levels. Displacing
      plasma ADMA by oral supplementation of L-arginine restores endothelial
      dysfunction by augmenting endothelial nitric oxide generation. Strict control of
      hyperglycemia decreases serum ADMA levels. These and other studies suggest that
      serum ADMA levels could be used to predict the development of hypertension and
      type 2 diabetes mellitus in those who are at high-risk to develop these diseases.

PMID- 21196156
TI  - Regulatory mechanism of osteoclastogenesis by RANKL and Wnt signals.
AB  - Osteoclasts develop from monocyte-macrophage lineage cells under the regulation
      of osteoblasts. Osteoblasts express two cytokines essential for
      osteoclastogenesis, macrophage colony-stimulating factor (M-CSF) and receptor
      activator of nuclear factor-KappaB ligand (RANKL). Osteoblasts also produce
      osteoprotegerin (OPG), a decoy receptor for RANKL, which inhibits the interaction
      between RANKL and RANK, a receptor of RANKL. Bone resorption-stimulating factors
      act on osteoblasts to regulate RANKL and OPG expression. Nuclear factor of
      activated T-cells, cytoplasmic 1 (NFATc1) is a master transcription factor for
      osteoclast differentiation. The immunoreceptor tyrosine-based activation motif
      (ITAM)-mediated signal was discovered as a co-stimulatory signal in RANKL-induced
      osteoclastogenesis. Wnt proteins activate two pathways: beta-catenin-dependent
      canonical and beta-catenin-independent noncanonical pathways. Wnt proteins
      promote differentiation of osteoblasts through the canonical pathway. The
      canonical pathway in osteoblasts also suppresses osteoclastogenesis through up
      regulation of OPG expression and down-regulation of RANKL expression. In
      contrast, activation of the noncanonical pathway in osteoclast precursors
      enhances RANKL-induced osteoclastic differentiation. Thus, Wnt signals in
      osteoblasts and osteoclast precursors play important roles in osteoclastogenesis.
      This review summarizes the regulatory mechanism of osteoclastogenesis by RANKL
      and Wnt signals.

PMID- 21196157
TI  - Angiogenic signaling aberrantly induced by tumor hypoxia.
AB  - Tumor growth, invasion and metastasis are largely dependent on the development of
      tumor vasculature. A great number of pro- and antiangiogenic molecules, have been
      identified. Bone marrow-derived cells are mobilized and recruited to angiogenic
      sites, by a variety of growth factors and cytokines, to promote angiogenesis and
      the formation of new blood vessels. The hypoxic microenvironment that is
      inevitably generated in solid tumors is a major contributor to tumor
      angiogenesis. Tumor hypoxia aberrantly modulates the expression of many potent
      pro- and antiangiogenic molecules, primarily through the action of heterodimeric
      transcription factors termed hypoxia-inducible factors, HIF-1 and HIF-2. The
      disruption of the balance between pro- and antiangiogenic activities eventually
      leads to a shift in balance to a more angiogenic state. These findings have
      provoked considerable interest in HIFs as attractive targets for cancer therapy.
      Consequently, the development of small molecule HIF inhibitors is currently
      moving ahead at a fast pace.

PMID- 21196158
TI  - Lipogenic effects of psychotropic drugs: focus on the SREBP system.
AB  - Antipsychotics, antidepressants and mood stabilizers are psychotropic drugs
      widely used in the treatment of psychiatric disorders, such as schizophrenia,
      bipolar disorder and major depressive disorder. Such drugs have been used since
      the early 1950s, and it is now well established that they target neurotransmitter
      receptors and/or transporters located on central nervous system (CNS) neurons.
      However, their mechanism of action is still not fully understood, and there is
      large inter-individual variation in therapeutic response. Psychotropic drugs are
      also associated with numerous adverse effects, of which weight gain and metabolic
      disturbances have gained increased focus during the last decade. Based on studies
      in cultured cells, we have demonstrated that several psychotropic drugs
      upregulate the expression of genes involved in cellular fatty acid and
      cholesterol biosynthesis, controlled by the SREBP transcription factors.
      Lipogenic effects were also observed in vivo, in rat liver and in lymphocytes
      from drug-treated patients. These results provide new insight into the molecular
      mechanisms of psychotropic drug action and could be relevant both for their
      therapeutic action and metabolic adverse effects.

PMID- 21196159
TI  - Biomolecular studies by circular dichroism.
AB  - In this review, we shall outline the basic principles of circular dichroism (CD)
      indicating the types of structural information relevant to the study of
      biomolecules, such as proteins or DNA. We are mainly interested to show the
      utility of this technique to study protein-ligand, DNA-ligand and protein-DNA
      interactions.

PMID- 21196162
TI  - Influence of polymorphisms on EGFR targeted therapy in non-small-cell lung
      cancer.
AB  - Non-small-cell-lung cancer (NSCLC) is the leading cause of cancer-related deaths.
      However, chemotherapy has reached a therapeutic plateau and deals with
      significant toxicity. Novel anticancer treatments to neutralize specific
      molecules or genes involved in cancer development ("targeted-therapy") are being
      developed to reduce side-effects and improve outcome. The epidermal-growth-factor
      receptor (EGFR) is over-expressed in NSCLC and emerged as an attractive target.
      Two classes of anti-EGFR agents (tyrosine-kinase-inhibitors and monoclonal
      antibodies) have shown clinical activity, depending on EGFR mutations and
      expression. However, clinical outcome, including tolerability, can not always be
      explained by these biomarkers. Thus, the identification of novel biomarkers is a
      viable area of research. Germline polymorphisms can be easily assessed, and
      polymorphisms in EGFR, AKT1 and ABCG2 have been correlated with outcome and
      toxicity in NSCLC patients given anti-EGFR therapies. However, there is lack of
      unanimity in findings, influenced by differences in study design/analysis, and
      the prognostic/predictive role of these polymorphisms needs to be evaluated
      within prospective studies. Finally, there is a critical need to conduct more
      studies on the relation of genotype with drug concentration/activity.

PMID- 21196161
TI  - TGF-beta-dependent and -independent roles of STRAP in cancer.
AB  - The serine-threonine kinase receptor-associated protein (STRAP) was initially
      identified as a putative inhibitor of the canonical TGF-beta signaling pathway.
      Because the Smad-dependent TGF-beta pathway negatively regulates cellular growth,
      early functional studies suggested that STRAP behaves as an oncogene. Indeed, a
      correlation between STRAP overexpression and various cancers has been identified.
      With the emergence of new studies on the biological function of STRAP, it is
      becoming clear that STRAP regulates several distinct cellular processes and
      modulates multiple signaling pathways. While STRAP itself does not possess
      enzymatic activity, it appears that STRAP influences biological processes through
      associations with cellular proteins. In this review, we will describe the TGF
      beta-dependent and -independent functions of STRAP and provide a context for the
      significance of STRAP activity in the development of cancer.

PMID- 21196163
TI  - Activity rhythms in the deep-sea: a chronobiological approach.
AB  - Ocean waters deeper than 200 m cover 70% of the Earth's surface. Light intensity
      gets progressively weaker with increasing depth and internal tides or inertial
      currents may be the only remaining zeitgebers regulating biorhythms in deep-sea
      decapods. Benthopelagic coupling, exemplified by vertically moving shrimps within
      the water column, may also act as a source of indirect synchronisation to the day
      night cycle for species living in permanently dark areas. At the same time,
      seasonal rhythms in growth and reproduction may be an exogenous response to
      spring-summer changes in upper layer productivity (via phytoplankton) or,
      alternatively, may be provoked by the synchronisation mediated by an endogenous
      controlling mechanism (via melatonin). In our review, we will focus on the
      behavioural rhythms of crustacean decapods inhabiting depths where the sun light
      is absent. Potential scenarios for future research on deep-sea decapod behaviour
      are suggested by new in situ observation technologies. Permanent video
      observatories are, to date, one of the most important tools for marine
      chronobiology in terms of species recognition and animals' movement tracking.

PMID- 21196164
TI  - The role of lipid rafts in prion protein biology.
AB  - The conformational conversion of the cellular prion protein, PrP(C), to the
      misfolded isoform PrP(Sc )is the central pathogenic event in the uniquely
      transmissible neurodegenerative prion diseases. As both PrP(C) and PrP(Sc) are
      associated with membranes, the nature of the membrane microenvironment may well
      play a significant role in both the conformational conversion process as well as
      the normal functions of PrP(C). Within the membrane are various microdomains,
      areas of distinct lipid and protein composition, the best studied of which are
      the cholesterol- and sphingolipid-rich lipid rafts. These domains are
      characterized biochemically by their relative resistance to solubilization in
      certain detergents at low temperature. In this article we review the evidence for
      the involvement of lipid rafts in the localization and trafficking of PrP(C), in
      the cellular signaling, neuroprotective and metal binding functions of PrP(C),
      and as sites for the conversion of PrP(C) to PrP(Sc) and in cell-to-cell prion
      transmission.

PMID- 21196160
TI  - Central neural pathways for thermoregulation.
AB  - Central neural circuits orchestrate a homeostatic repertoire to maintain body
      temperature during environmental temperature challenges and to alter body
      temperature during the inflammatory response. This review summarizes the
      functional organization of the neural pathways through which cutaneous thermal
      receptors alter thermoregulatory effectors: the cutaneous circulation for heat
      loss, the brown adipose tissue, skeletal muscle and heart for thermogenesis and
      species-dependent mechanisms (sweating, panting and saliva spreading) for
      evaporative heat loss. These effectors are regulated by parallel but distinct,
      effector-specific neural pathways that share a common peripheral thermal sensory
      input. The thermal afferent circuits include cutaneous thermal receptors, spinal
      dorsal horn neurons and lateral parabrachial nucleus neurons projecting to the
      preoptic area to influence warm-sensitive, inhibitory output neurons which
      control thermogenesis-promoting neurons in the dorsomedial hypothalamus that
      project to premotor neurons in the rostral ventromedial medulla, including the
      raphe pallidus, that descend to provide the excitation necessary to drive
      thermogenic thermal effectors. A distinct population of warm-sensitive preoptic
      neurons controls heat loss through an inhibitory input to raphe pallidus neurons
      controlling cutaneous vasoconstriction.

PMID- 21196165
TI  - Understanding the neurospecificity of Prion protein signaling.
AB  - The cellular prion protein PrP(C) is the normal counterpart of the scrapie prion
      protein PrP(Sc), the main component of the infectious agent of transmissible
      spongiform encephalopathies (TSEs). It is a ubiquitous cell-surface glycoprotein,
      abundantly expressed in neurons, which constitute the targets of TSE
      pathogenesis. The presence of PrP(C) at the surface of neurons is an absolute
      requirement for the development of prion diseases and corruption of PrP(C)
      function(s) within an infectious context emerges as a proximal cause for PrP(Sc)
      induced neurodegeneration. Experimental evidence gained over the past decade
      indicates that PrP(C) has the capacity to mobilize promiscuous signal
      transduction cascades that, notably, contribute to cell homeostasis. Beyond
      ubiquitous effectors, much data converge onto a neurospecificity of PrP(C)
      signaling, which may be the clue to neuronal cell demise in prion disorders. In
      this article, we highlight the requirement of PrP(C) for TSEs-associated
      neurodegeneration and review the current knowledge of PrP(C)-dependent signal
      transduction in neuronal cells and its implications for PrP(Sc)-mediated
      neurotoxicity.

PMID- 21196166
TI  - Telomere protein complexes and interactions with telomerase in telomere
      maintenance.
AB  - Telomeres are the termini of linear chromosomes. They are composed of DNA and DNA
      binding proteins critical for maintaining chromosome integrity and cellular
      function. Telomere binding proteins regulate the structure and function of
      telomeres through the formation of different complexes with telomeric DNA. Double
      and single-stranded telomeric DNA binding protein complexes have shared and
      unique functions that regulate telomere homeostasis. Recent studies have shown
      that telomerase interacts with several telomere-binding protein complexes
      including shelterin, CST, DNA-dependent protein kinase (DNA-PK) and MRN. The
      present review describes the recognised telomere-binding protein complexes, sub
      complex exchanges and inter-complex molecular interactions. It also discusses the
      evidence suggesting that telomerase reverse transcriptase (TERT) switches between
      different complexes. Studies of the telomere protein inter-complex interactions
      and the switching of components between complexes provide insight into their
      fundamental roles of programming telomere length and configuration, and thus cell
      proliferative potential.

PMID- 21196167
TI  - Approaches to improve photodynamic therapy of cancer.
AB  - Photodynamic therapy (PDT) is a clinically approved method of tumor treatment.
      Its unique mechanism of action results from minimal invasiveness and high
      selectivity towards transformed cells. However, visible light used to excite most
      photosensitizers has rather limited ability to penetrate tissues resulting in
      insufficient destruction of deeply seated malignant cells. Therefore, novel
      strategies for further potentiation of the anticancer effectiveness of PDT have
      been developed. These include combined treatments with surgery, chemo- and
      radiotherapy, strategies targeting cytoprotective mechanisms induced in PDT
      treated cells, as well as attempts aimed at enhancement of PDT-mediated antitumor
      immune response. Moreover, new photosensitizers and novel light sources are being
      developed. Impressive progress in nanotechnology and understanding of tumor cell
      biology rise hopes for further improvements in this elegant and promising method
      of cancer treatment.

PMID- 21196168
TI  - Chronic viral hepatitis: epidemiology, molecular biology, and antiviral therapy.
AB  - Viral hepatitis is a major cause of chronic liver disease, liver failure, and
      hepatocellular carcinoma worldwide, resulting in significant morbidity and
      mortality. New insights into the pathogenesis and molecular biology of hepatitis
      viruses have led to the discovery of novel antiviral agents. Likewise, a greater
      understanding of the natural history of chronic infection, predictors of disease
      progression, and predictors of virologic response to therapy has resulted in more
      effective treatment strategies. Recent data have increasingly demonstrated that
      the ability to achieve a successful response to antiviral therapy may
      significantly reduce the risk of progressive liver disease and hepatocellular
      carcinoma. Immunization practices and the use of potent antiviral therapy may
      have a major impact in reducing the burden of chronic liver disease and the
      incidence of hepatocellular carcinoma associated with chronic hepatitis B and
      chronic hepatitis D. Individualized treatment strategies and the development of
      direct acting antiviral agents may lead to further improvements in the ability to
      achieve a sustained virologic response to therapy in chronic hepatitis C. With
      new advances in the treatment of chronic hepatitis, efforts to optimize viral
      suppression while reducing the potential for antiviral drug resistance will
      become increasingly important.

PMID- 21196169
TI  - Role of estrogen receptors alpha, beta and GPER1/GPR30 in pancreatic beta-cells.
AB  - Estrogen receptors (ER) are emerging as important molecules involved in the
      adaptation of beta-cells to insulin resistance. The onset of type 2 diabetes is
      marked by insulin secretory dysfunction and decreased beta-cell mass. During
      pregnancy, puberty and obesity there is increased metabolic demand and insulin
      resistance is developed. This metabolic state increases the demand on beta-cells
      to augment insulin biosynthesis and release. In this respect, ERalpha is directly
      implicated in the E2-regulation of insulin content and secretion, while ERbeta is
      in the E2-potentiation of glucose-induced insulin release. Both receptors develop
      their actions within the physiological range of E2. In addition, the G protein
      coupled estrogen receptor (GPER1/GPR30) seems to be implicated in the E2
      regulation of stimulus-secretion coupling in the three cell types of the islet.
      The increased demand of insulin production for long time may lead to beta-cell
      stress and apoptosis. ERalpha, ERbeta and GPER1/GPR30 are involved in preventing
      beta-cell apoptosis, impeding the loss of critical beta-cell mass. Therefore,
      estrogen receptors may play an essential role in the adaptation of the pancreas
      to insulin resistant periods.

PMID- 21196170
TI  - Hyaluronan and mesenchymal stem cells: from germ layer to cartilage and bone.
AB  - A simple, linear polysaccharide with unique molecular functions, hyaluronan is a
      glycosaminoglycan whose biomechanical and hydrodynamic properties have been
      thoroughly characterized. However, the exact role the molecular mechanisms and
      signaling pathways of hyaluronan play in the regulation of stem cell fate, such
      as self-renewal and differentiation, remains to be determined. The abundance of
      hyaluronan in embryonic tissues indicates that it is highly important in
      developmental processes. Recent studies have focused on understanding the
      mechanisms of hydrated hyaluronan action and its interaction with neighboring
      substances. This review is an attempt to elucidate the complex role of hyaluronan
      signaling in the initialization and regulation of developmental processes,
      particularly in events dictating the fates of mesenchymal stem cells during the
      organogenetic phases of chondrogenesis and osteogenesis.

PMID- 21196171
TI  - Molecular mechanisms of the antitumor effects of anti-CD20 antibodies.
AB  - Anti-CD20 monoclonal antibodies (mAbs) have become the mainstay in the treatment
      of non-Hodgkin's lymphomas and have shown significant activity in patients with B
      cell chronic lymphocytic leukemia. Antitumor action of these antibodies results
      from triggering of indirect effector mechanisms of the immune system that include
      activation of complement-dependent cytotoxicity (CDC), antibody-dependent
      cellular cytotoxicity (ADCC), or phagocytosis. Moreover, some studies indicate
      direct influence of anti-CD20 mAbs on tumor cells that leads to induction of
      various types of cell death. Despite the wealth of data on the mechanisms of
      cytotoxicity that accumulated over the last two decades their relative
      contribution to the therapeutic outcome is still difficult to predict in
      individual patients. Elucidation of molecular mechanisms of anti-CD20 mAbs action
      is necessary to deliver their maximal activity in rationally designed
      combinations with other therapeutic approaches and to design next generation anti
      CD20 mAb with improved ability to eliminate tumor cells.

PMID- 21196172
TI  - Timing is everything: stochastic origins of cell-to-cell variability in cancer
      cell death.
AB  - The diversity of cell populations is regulated by extracellular and intracellular
      variability. The latter includes genetic, epigenetic and stochastic variability,
      all contributing to the experimentally observed heterogeneity in response to
      external death-inducing stimuli. Studies of sources and regulation of variability
      in commitment to apoptotic cancer cell death are likely to identify the
      fundamental features of apoptotic protein networks that are responsible for
      determining the ultimate cell fate. Systems biology approaches, involving
      computer simulations of the biochemical reactions accompanied, if possible, by
      experimental verification of selected components of the model, are proving useful
      in determining the origins of cell-to-cell variability in response to external
      stress stimuli. Here we summarize our current understanding of the origins of
      stochastic variability in cells' commitment to apoptosis, and its implications in
      the field on cancer therapy.

PMID- 21196173
TI  - Amino acids and diabetes: implications for endocrine, metabolic and immune
      function.
AB  - Aberrant alterations in glucose and lipid concentrations and their pathways of
      metabolism are a hallmark of diabetes. However, much less is known about
      alterations in concentrations of amino acids and their pathways of metabolism in
      diabetes. In this review we have attempted to highlight, integrate and discuss
      common alterations in amino acid metabolism in a wide variety of cells and
      tissues and relate these changes to alterations in endocrine, physiologic and
      immune function in diabetes.

PMID- 21196174
TI  - HDACi--going through the mechanisms.
AB  - Histone deacetylases inhibitors (HDACi) have recently emerged as potent antitumor
      treatment modality. They are currently tested in many phase I, II and III
      clinical trials as single agents as wells as in combination schemes. They have
      demonstrated promising antitumor activity and favorable clinical outcome. Histone
      deacetylases (HDACs) are involved in the process of epigenetic regulation of gene
      expression. Epigenetic changes are believed to be crucial for the onset and
      progression of cancer and have recently gained remarkable attention. Since
      epigenetic regulation of gene expression is a reversible process, targeting
      histone deacetylases provides a good rationale for anticancer therapy. The
      acetylation status of histones regulates the organization of chromatin and the
      access of transcription factors. Moreover, functions of many non-histone proteins
      are controlled by acetylation. The broad and complicated influences of HDACi on
      various molecular processes may account for the observed pleiotropic effects. In
      this review we summarize recent advances in the understanding of biology of HDACs
      and mechanism of action of their inhibitors.

PMID- 21196175
TI  - Heterogeneous modes of insulin granule exocytosis: molecular determinants.
AB  - Glucose-induced insulin secretion is biphasic: the first phase forms a transient
      peak of secretion lasting a few minutes after the stimulation, whereas the second
      maintains a lower but persistent secretion rate. It was suggested that two
      different exocytic mechanisms operate during the two phases: the first phase
      exocytosis is derived from docked granules, whereas the second derives from newly
      recruited granules. However, total internal reflection fluorescence microscopy
      has revealed that, while the exocytosis in the first few minutes is derived from
      granules located close to the plasma membrane, it is also significantly effected
      by deeper granules, whereas that in the second phase is mainly derived from the
      deeper granules. Consistently, pancreatic beta cells deficient in the Rab27a
      effector, granuphilin, which is indispensable for the stable attachment (docking)
      of insulin granules to the plasma membrane, exhibit no delay or reduction of
      secretagogue-induced insulin secretion, and instead exhibit increased secretion.
      Future studies should explore the mechanism for time-dependent differences in the
      exocytic behaviors, namely the molecular determinants of the rate-limiting
      exocytic steps for docked and undocked granules.

PMID- 21196176
TI  - Evidence for cancer stem cells contributing to the pathogenesis of ovarian
      cancer.
AB  - Ovarian cancer represents the most lethal gynecologic malignancy, primarily due
      to a lack of early detection, which results in most patients being diagnosed at
      an advanced stage of disease. Though the ovarian surface epithelium is thought to
      provide the primary site of tumorigenesis, the exact etiology of the various
      tumor types associated with this disease remain undefined. Recent evidence
      suggests that ovarian tumors, like other solid tumors, contain distinct
      populations of cells that are responsible for tumor initiation, maintenance and
      growth. These specialized cells, termed cancer stem cells, display some of the
      hallmarks of normal stem cells and are thought to evade current chemotherapeutic
      strategies, resulting in an increased risk of recurrence. Here we review evidence
      for the existence of cancer stem cells in ovarian malignancies and their
      contribution to the pathology of this disease, critically evaluate the methods
      used for ovarian cancer stem cell definition and isolation, and discuss their
      clinical relevance.

PMID- 21196179
TI  - A minireview: the role of MAPK/ERK and PI3K/Akt pathways in thyroid follicular
      cell-derived neoplasm.
AB  - The MAPK/ERK (mitogen - activated protein kinase/extracellular signal-regulated
      kinase signaling pathway) and PI3K/Akt (lipid kinase phoshoinositide-3-kinase
      signaling pathway) play an important role in transmission of cell signals through
      transduction systems (ligands, transmembrane receptors and cytoplasmic secondary
      messengers) to cell nucleus, where they influence the expression of genes that
      regulate important cellular processes: cell growth, proliferation and apoptosis.
      The genes, coding the signaling cascade proteins (e.g., RET, RAS, BRAF, PI3K,
      PTEN, AKT), are mutated or aberrantly expressed in thyroid cancer derived from
      follicular thyroid cell. Genetic and epigenetic alternations, concerning MAPK/ERK
      and PI3K/Akt signaling pathways, contribute to their activation and interaction
      in consequence of malignant follicular cell transformation. This review is
      focused mainly on genetic alterations in genes, coding signaling pathway
      proteins. Moreover, it is additionally pointed out that genetic, as well as
      epigenetic DNA changing via aberrant methylation of several tumour suppressor and
      thyroid-specific genes are associated with tumour aggressiveness, being a jointly
      responsible mechanism for thyroid tumorigenesis. The understanding of this
      molecular mechanism provides access to novel molecular therapeutic strategies for
      inhibiting oncogenic activity of signaling pathways.

PMID- 21196177
TI  - Molecular imaging metrics to evaluate response to preclinical therapeutic
      regimens.
AB  - Molecular imaging comprises a range of techniques, spanning not only several
      imaging modalities but also many disease states and organ sites. While advances
      in new technology platforms have enabled a deeper understanding of the cellular
      and molecular basis of malignancy, reliable non-invasive imaging metrics remain
      an important tool for both diagnostics and patient management. Furthermore, the
      non- invasive nature of molecular imaging can overcome shortcomings associated
      with traditional biological approaches and provide valuable information relevant
      to patient care. Integration of information from multiple imaging techniques has
      the potential to provide a more comprehensive understanding of specific tumor
      characteristics, tumor status, and treatment response.

PMID- 21196178
TI  - Receptor-mediated T cell absorption of antigen presenting cell-derived molecules.
AB  - T cells tend to acquire a variety of cell surface molecules derived from antigen
      presenting cells (APCs). The molecule uptake occurs mainly during direct T/APC
      contact and is instigated by specific receptor/ligand interactions, such as T
      cell receptor (TCR) with a cognate peptide/MHC complex (pMHC) or CD28 with B7.
      The acquired molecules are targeted for internalization and degradation in the
      lysosome. Nevertheless, those molecules are expressed on the surface of T cells
      for a period of time. The presentation of APC-derived ligands by T cells
      exhibited a multitude of immunological effects via antigen-specific T/T
      interaction upon recognition of the absorbed antigens by contact with other T
      cells. Ligand uptake also occurs via absorption of membrane vesicles shed from
      APCs prior to contact (e.g., exosomes and plasma membrane-derived vesicles). As
      in ligand absorption via direct T/APC interaction, the absorption of pre-formed
      membrane vesicles is also dependent on specific receptor/ligand interactions. In
      this review, biological mechanisms underlying the ligand absorption process as
      well as the biological significance and application of the event will be
      discussed.

PMID- 21196180
TI  - The regulation of cell growth and survival by aldosterone.
AB  - The steroid hormone aldosterone is synthesized from cholesterol, mainly in the
      zona glomerulosa of the adrenal cortex. Aldosterone exerts its effects in the
      epithelial tissues of the kidney and colon and in non-epithelial tissues such as
      the brain and cardiovasculature. The genomic response to aldosterone involves
      dimerization of the mineralocorticoid receptor (MR), dissociation of heat shock
      proteins from MR, translocation of the aldosterone-MR complex to the nucleus and
      the concomitant regulation of gene expression. Rapid responses to aldosterone
      occur within seconds to minutes, do not involve transcription or translation and
      can modulate directly or indirectly the later genomic responses. Aside from the
      well-known effects of aldosterone on the regulation of sodium and water
      homeostasis, aldosterone can also produce deleterious structural changes in
      tissues by inducing hypertrophy and the dysregulation of proliferation and
      apoptosis, leading to fibrosis and tissue remodelling. Here we discuss the
      involvement of aldosterone-mediated rapid signalling cascades in the development
      of disease states such as chronic kidney disease and heart failure, and the
      antagonists that can inhibit these pathophysiological responses.

PMID- 21196181
TI  - Crystalline calcium carbonate and hydrogels as microenvironment for stem cells.
AB  - Stem cell development and fate decisions are dictated by the microenvironment in
      which the stem cell is embedded. Among the advanced goals of tissue engineering
      is the creation of a microenvironment that will support the maintenance and
      differentiation of the stem cell--based on embryonic and adult stem cells as
      potent, cellular sources--for a variety of clinical applications. This review
      discusses some of the approaches used to create regulatory and instructive
      microenvironments for the directed differentiation of mesenchymal stem cells
      (MSCs) using three-dimensional crystalline calcium carbonate biomaterials of
      marine origin combined with a hydrated gel based on hyaluronan.

PMID- 21196182
TI  - Signalling pathways that regulate endothelial differentiation from stem cells.
AB  - Endothelial cells play a vital role in the human vascular system. Injury to this
      layer of cells can lead to devastating consequences and eventually mortality. As
      demonstrated by recent accumulating evidences, the injured endothelial layer can
      be rescued by endothelial cell-based therapy. However, the limited source of
      functional endothelial cells which can be used in clinical surgery, is hugely
      hampered. The discovery of pluripotent embryonic stem cells, nevertheless has
      raised hope for generating endothelial cells in the regenerative medicine field.
      It was demonstrated that the concerted and coordinated series of specific
      signaling pathways involving different molecules, guide the differentiation of
      these embryonic stem cells into functional endothelial cells. Moreover, it is
      believed that understanding the molecular mechanisms of endothelial development
      and signal pathways leading to endothelial differentiation from stem cells, will
      be essential for potential cell therapy for vascular disease. This review
      therefore, will summarize and discuss recent insights into endothelial
      development and the signaling pathways regulating embryonic stem cell
      differentiation towards the endothelial lineage.

PMID- 21196183
TI  - RAGE and cardiovascular disease.
AB  - RAGE is pattern recognizing receptors for diverse endogenous ligands. RAGE
      activation by RAGE ligands is known to be associated with reactive oxygen species
      generation, activation of NF kappa B, as well as recruitment of proinflammatory
      cells. Activated endothelial cells, vascular smooth muscle cells in
      atherosclerotic plaques and activated inflammatory cells all have increased
      expression of RAGE, which with its interaction with RAGE ligands increases the
      secretion of proinflammatory cytokines and cell adhesion molecules. Furthermore,
      RAGE may have a significant role in leukocyte recruitment into the intima of the
      atherosclerosis. Initial insults resulting in endothelial dysfunction will result
      in leukocyte infiltration, oxidative stress and vascular inflammation that is
      amplified by RAGE activation. RAGE and its interaction with RAGE ligands may be
      important for initializing and maintaining the pathological processes that result
      in various entities of cardiovascular disease. Soluble RAGE competitively
      inhibits the binding of RAGE ligands to RAGE and attenuates the development of
      atherosclerosis in vivo. Thus RAGE may be a promising target for treatment of
      cardiovascular disease in the future.

PMID- 21196184
TI  - The manifold actions of endocannabinoids on female and male reproductive events.
AB  - Epidemiological studies have highlighted the ever growing use of illegal drugs
      among teenagers. The negative effects of marijuana (a Cannabis sativa extract) on
      reproductive health are poorly known among young people, although chronic
      exposure to delta-9-tetrahydrocannabinol, the main psychoactive constituent of
      marijuana, impairs human reproductive potential by disrupting menstrual cycle,
      suppressing oogenesis and impairing embryo implantation and development, in
      women, and by increasing ejaculation problems, reducing sperm count and motility,
      and generating loss of libido and impotence, in men. Endocannabinoids, their
      metabolic enzymes and target receptors form the so called "endocannabinoid
      system" and they have been demonstrated to respond to fertility signals. In
      addition, they interfere with hormones, cytokines and other signalling molecules
      in both female and male reproductive events. In this review, we shall summarize
      the current knowledge on the endocannabinoid system, and on the multifaceted
      roles played by endocannabinoids in reproduction along the evolutionary axis from
      invertebrates to mammals. Furthermore, we shall discuss the potential use of
      distinct elements of the endocannabinoid system for the diagnosis and/or
      treatment of human infertility.

PMID- 21196185
TI  - Functional role of Akt in macrophage-mediated innate immunity.
AB  - Akt (protein kinase B) is a serine/threonine protein kinase that regulates cell
      metabolism, survival and proliferation. Recent studies of the role of Akt in
      phagocytosis, intracellular bacterial infections, LPS tolerance, production of
      inflammatory cytokines and mediators, and migration during macrophage-mediated
      innate immunity strongly suggest a pivotal role for this enzyme in the functional
      activation of macrophages. Considering that a variety of inflammatory diseases,
      such as rheumatoid arthritis, atherosclerosis, diabetes, obesity, cancer and
      osteoporosis, are regulated by macrophage-mediated innate immunity, efforts
      should be more carefully focused on understanding the function of Akt in
      macrophage-mediated innate immunity. Although few studies have addressed this
      question, this review discusses recent findings that support an important role
      for Akt in macrophage-mediated innate immunity and underlines the need for trials
      to develop pharmaceutically useful drugs that target Akt for treatment of
      macrophage-mediated inflammatory diseases. The findings we review here suggest
      that a novel and safe Akt inhibitor with strong immunosuppressive and anti
      inflammatory properties will be applied to various chronic inflammatory diseases
      in the near future.

PMID- 21196186
TI  - Growth Factors and their receptors in cancer metastases.
AB  - Metastatic, rather than primary tumours are responsible for ninety percent cancer
      deaths. Despite significant advances in the understanding of molecular and
      cellular mechanisms in tumour metastases, there are limitations in preventive
      treatment of metastatic tumours. Much evidence arising from laboratory and
      clinical studies suggests that growth factors and their receptors are implicated
      in cancer metastases development. We review the origin and production of growth
      factors and their receptors in all stages of cancer metastases including
      epithelial-mesenchymal transition, cancer cell invasion and migration, survival
      within the circulation, seeding at distant organs and metastatic tumour
      angiogenesis. The functions of growth factors and their receptors are also
      discussed. This review presents the efforts made in understanding this challenge
      to aid in the development of new treatment strategies for cancer metastases.

PMID- 21196187
TI  - Type II transmembrane serine protease (TTSP) deregulation in cancer.
AB  - The Type II transmembrane serine proteases (TTSP) are a relatively newly
      identified family of proteolytic enzymes that have become the subject of intense
      scrutiny in the field of cancer research. Advances in genome screening technology
      have enabled the identification of putative members and the further
      characterization of existing members. The TTSPs are involved in a diverse range
      of physiological functions and new roles continue to be discovered. A large
      majority of these proteases appear to play crucial roles in the development of
      disease, especially cancer development and progression. This review presents the
      current knowledge of the biological role of those TTSPs that have been identified
      in the development and progression of human cancers.

PMID- 21196188
TI  - Modulation of cardiac ryanodine receptor activity by ROS and RNS.
AB  - Calcium release through cardiac ryanodine receptors (RyR2) triggers heart muscle
      contraction. Reactive oxygen/nitrogen species (ROS/RNS), normally produced in the
      heart, promote endogenous RyR2 S-nitrosylation and S-glutathionylation. These
      reversible redox modifications increase RyR2 activity in vitro, and presumably
      also in vivo. RyR2 S-glutathionylation increases under physiologically relevant
      conditions (tachycardia and exercise), suggesting that cardiac cells utilize this
      redox modification to increase RyR2 activity under increased demand. In contrast,
      in vivo changes in RyR2 S-nitrosylation in response to physiological stimuli
      remain uncharacterized. The number and identity of the highly reactive RyR2
      cysteine residues and the nature of the redox modification they undergo are
      presently unknown. Likewise, the physiological sources of ROS/RNS responsible for
      functionally relevant RyR2 redox modifications have not been completely
      identified. The redox state of RyR2 is altered in heart failure leading to
      enhanced RyR2 activity, which presumably contributes to decrease SR calcium
      content and induce other calcium release abnormalities observed in heart failure.
      Greater understanding of RyR2 redox modulation is necessary to counteract the
      deleterious consequences of RyR2 activity deregulation caused by oxidative
      stress.

PMID- 21196189
TI  - Redox sensitive Pyk2 as a target for therapeutics in breast cancer.
AB  - Breast cancer progression is dependent on the formation of new blood vessels that
      not only help the tumor by supplying additional nutrients, but also allow cancer
      cells to spread from the breast to distant sites in the body. Several studies
      suggest a positive correlation between new vessel formation and estrogens.
      Estrogenic environmental chemicals such as PCBs have been shown to increase the
      expression of factors known to promote vessel formation in breast tumors. These
      studies highlight a growing concern that women exposed to estrogenic
      environmental compounds may be more susceptible to either aggressive metastatic
      tumors or a high recurrence of breast cancer. Our concept offers a fundamental
      new understanding of the way the environment contributes to breast cancer
      progression. This review will be focused on a highly novel Pyk2 signaling complex
      as a target for therapy of estrogen dependent breast tumor angiogenesis. A better
      understanding of the role of Pyk2 signaling in estrogen dependent tumor
      vascularization may lead to the development of a new therapy against aggressive
      breast cancer using small molecule inhibitors of Pyk2.

PMID- 21196190
TI  - Regulation of protein metabolism by glutamine: implications for nutrition and
      health.
AB  - Glutamine is the most abundant free alpha-amino acid in plasma and skeletal
      muscle. This nutrient plays an important role in regulating gene expression,
      protein turnover, anti-oxidative function, nutrient metabolism, immunity, and
      acid-base balance. Interestingly, intracellular and extracellular concentrations
      of glutamine exhibit marked reductions in response to infection, sepsis, severe
      burn, cancer, and other pathological factors. This raised an important question
      of whether glutamine may be a key mediator of muscle loss and negative nitrogen
      balance in critically ill and injured patients. Therefore, since the initial
      reports in late 1980s that glutamine could stimulate protein synthesis and
      inhibit proteolysis in rat skeletal muscle, there has been growing interest in
      the use of this functional amino acid to improve protein balance under various
      physiological and disease conditions. Although inconsistent results have appeared
      in the literature regarding a therapeutic role of glutamine in clinical medicine,
      a majority of studies indicate that supplementing appropriate doses of glutamine
      to enteral diets or parenteral solutions is beneficial for improving nitrogen
      balance in animals or humans with glutamine deficiency.

PMID- 21196191
TI  - Self-renewal mechanisms in neural cancer stem cells.
AB  - The view that there are cancer-initiating stem cells has led to a concerted
      effort to understand the nature of these cells. As in many tissues, rare
      populations of cancer stem cells have been characterized in neural cancers,
      including glioblastoma, medulloblastoma and epyndymoma. The ability of stem cells
      to undergo both symmetric (self-renewal) and asymmetric (division to produce a
      more differentiated cell) cell division is what defines them as stem cells.
      Understanding the molecular genetic mechanisms governing the self-renewal and
      proliferation of these cells will be important in developing novel more effective
      strategies which will perhaps lead to better treatments for many cancers,
      including some of the most difficult to treat, such as the most common and
      aggressive brain cancer, glioblastoma. This review will focus on the molecular
      genetic mechanisms which have recently been identified as being important for
      neural stem cell self-renewal in brain cancer.

PMID- 21196192
TI  - Modulation of programmed cell death pathways by the hepatitis C virus.
AB  - Hepatitis C virus (HCV), a positive stranded RNA virus of the family
      Flaviviridae, is the major cause of non-A, non-B hepatitis worldwide. The HCV
      genome encodes a precursor polyprotein of ~ 3,000 amino acids that is processed
      co-translationally and post-translationally to give rise to viral structural and
      non-structural proteins. Nearly all of these viral proteins have been shown to
      modulate cell death via various mechanisms. In addition, studies using the
      replicon and recombinant HCV cell culture systems have yield important insights
      into the modulation of programmed cell death by HCV replication. Here, we
      summarize current knowledge on the modulation of apoptosis and other programmed
      cell death pathways by the HCV in these cell culture systems.

PMID- 21196193
TI  - Proteins, glycerolipids and carotenoids in the functional photosystem II
      architecture.
AB  - Photosystem II (PSII), the first supercomplex of the electron transport chain,
      governs the energy transfer using harvested light energy, which is transformed
      into biochemical energy. Phosphatidylglycerol and sulfoquinovosyl diacylglycerol,
      the anionic lipids of photosynthetic organisms, together with a neutral lipid,
      digalactosyldiacylglycerol, assist in the assembly of photosynthetic complexes.
      These lipids and carotenoids serve as mortar for the proteins which act as bricks
      in the construction of the active photosynthetic machinery, and they have
      determinative roles in the oligomerization of protein subunits. X-ray
      crystallographic localization of glycerolipids and carotenoids revealed that they
      are present at functionally and structurally important sites of both the PSI and
      PSII reaction centers. Phosphatidylglycerol is involved in the formation of the
      reaction-center oligomers and controls electron transport at the acceptor site of
      PSII. Digalactosyldiacylglycerol, together with phosphatidylglycerol, is involved
      in the electron transport at the donor site. Phosphatidylglycerol and carotenoids
      are needed to glue CP43 to the reaction center core. Carotenoids are protective
      agents, which prevent photosynthetic complexes from degradation caused by
      reactive oxygen species.

PMID- 21196194
TI  - Regulation of VSMC behavior by the cadherin-catenin complex.
AB  - Vascular smooth muscle cells (VSMCs) are the predominant cell type within blood
      vessels. In normal vessels VSMC have low rates of proliferation, migration and
      apoptosis. However, increased VSMC proliferation, migration, and apoptosis rates
      radically alter the composition and structure of the blood vessel wall and
      contribute to vascular diseases such as atherosclerosis, in-stent restenosis and
      vein graft failure. Consequently, therapies that modulate VSMC proliferation,
      migration and apoptosis may be useful for treating vascular diseases. In this
      review article we discuss recently emerging research that has revealed that
      homophilic cell-cell contacts mediated by the cadherin:catenin complex and
      Wnt/beta-catenin signalling are important regulators of VSMC behaviour.

PMID- 21196195
TI  - Matricryptins derived from collagens and proteoglycans.
AB  - Controlled proteolysis of extracellular matrix components releases bioactive
      fragments or unmasks cryptic sites that play key roles in controlling various
      physio-pathological processes including angiogenesis, tissue remodeling, wound
      healing, inflammation, tumor growth, and metastasis. We review here the structure
      and mechanisms of release of i) the proteolytic fragments (matricryptins) cleaved
      from collagens, proteoglycans and glycosaminoglycans, and ii) the matricryptic
      sites existing in these molecules. The cell surface receptors and the signaling
      pathways they trigger to exert their biological activities is discussed with the
      major physio-pathological processes they control. Their involvement in autoimmune
      and inherited diseases is reported. Most matricryptins issued from collagens,
      proteoglycans and glycosaminoglycans exhibit anti-angiogenic and anti-tumor
      properties and their use as potential drugs and as potential disease markers is
      discussed. Perspectives for identifying the common structural features, if any,
      of the matricryptins and their use in combination with chemotherapy and
      radiotherapy in the treatment of cancer are presented.

PMID- 21196196
TI  - Cryptic activities of fibronectin fragments, particularly cryptic proteases.
AB  - Fibronectin (FN) is a modular glycoprotein encoded by a single gene. A soluble
      form of this protein is found in the plasma of several animals. Alternative
      splicing of pre-mRNA at three sites produces cellular and plasma FNs. The plasma
      form contributes to blood clotting and thrombosis. Many extracellular matrices
      (ECM) contain an FN network associated with a variety of cell activities through
      binding to cell surface integrin receptors. Fragments of FN can have cryptic
      activities that are specific to these fragments rather than to the intact
      protein. The metalloprotease activity present in the basement membrane and plasma
      fibronectins has been intensively studied in humans, bovine and rats. Organic
      inhibitors that are selective for the human cryptic enzyme have been produced.

PMID- 21196197
TI  - The cell-elastin-elastase(s) interacting triade directs elastolysis.
AB  - Human elastases have been identified within serine, cysteine and metallopeptidase
      families. These enzymes are able to adsorb rapidly onto elastin, but they can
      also bind onto cell surface-associated proteins such as heparan sulfate
      proteoglycans, both interactions involving enzyme exosites distinct form active
      site. Immobilization of elastin at the cell surface will create a sequestered
      microenvironment and will favour elastolysis. Generated elastin peptides are
      potent matrikines displaying dual biological functions in physiopathology that
      are described in this review. Among properties, they are potent inducers of
      protease expression catalyzing collagenolysis or amplifying elastin degradation.
      The ability of unsaturated fatty acids and heparin(s) to control elastases action
      are delineated.

PMID- 21196198
TI  - Lymphangiogenesis and cancer metastasis.
AB  - Lymphangiogenesis remains a fascinating biological process that plays a crucial
      role in both normal tissue development and several lymphatic diseases. The last
      few years have witnessed a rapid progression in understanding the development and
      regulation of the lymphatic system which provided insight on several pathological
      processes including cancer lymphatic metastasis. Lymphatic vasculature serves as
      a major route for tumour metastasis. The dissemination of malignant cells to the
      regional lymph nodes is an early step in the progression of many solid tumours
      and is an important determinant of staging and prognosis. Lymphangiogenesis is
      thought to play a pivotal role for cancer cells to metastasis to the regional
      lymph nodes. Several human solid tumours are now considered to be lymphangiogenic
      i.e. they have the ability to induce their own lymphatic vessels to establish
      metastasis. Hence, targeting lymphangiogenesis by developing anti-lymphangiogenic
      agents might constitute a novel way to prevent lymphatic progression in some
      tumours. Here, we have reviewed the development of the lymphatic system, the
      regulation of lymphangiogenesis and explored its relation to several human
      cancers.

PMID- 21196199
TI  - Antiangiogenic therapies for malignant pleural mesothelioma.
AB  - Malignant pleural mesothelioma (MPM), arises from the mesothelial cells, is
      difficult to be diagnosed at an early stage, and is refractory to conventional
      chemotherapy and radiotherapy. Therefore, the establishment of novel effective
      therapies is necessary to improve the prognosis for many patients with this
      disease. Recent studies have demonstrated that angiogenesis plays a significant
      role in MPM progression, suggesting the importance of tumor vessels as
      therapeutic targets. To explore molecular pathogenesis and evaluate the efficacy
      of vascular targeting therapy in MPM, we developed orthotopic implantation SCID
      mouse models of MPM. We found that selective VEGF inhibitors were effective only
      in the treatment of high-VEGF-producing MPM models. On the other hand, multiple
      kinase inhibitor E7080, with inhibitory activity against various angiogenic
      cytokine receptors, suppressed the progression and prolonged survival of both
      high-VEGF-producing and low-VEGF-producing MPM models. Further understanding of
      the functional characteristics of tumor angiogenesis may be essential to improve
      targeting therapies in MPM. In this review, we introduce current status of
      clinical strategies and novel therapeutic approaches against angiogenesis in MPM.

PMID- 21196200
TI  - Micromanagement of the mitochondrial apoptotic pathway by p53.
AB  - It is now well established that p53 is the primary arbiter of stress-response and
      the principal barrier to neoplastic processes at the cellular level. Perhaps the
      most potent weapon in p53's tumor suppressive arsenal is apoptosis, enacted as a
      last resort when all other remedies are exhausted. Initially, the mechanism was
      thought to be simply activation or repression of Bcl-2 family members by p53.
      More recently, evidence of a more rapid pathway emerged whereby p53 physically
      interacts with Bcl-2 family members to tip the balance toward apoptosis. This
      review details the multiple levels of regulation of mitochondrially-directed
      apoptosis by p53, including recent findings of how p53 translocation is
      regulated.

PMID- 21196201
TI  - Chemoprevention of hepatocellular carcinoma by acyclic retinoid.
AB  - The prognosis for patients with hepatocellular carcinoma (HCC) is poor and
      effective prevention strategies are urgently required. Here, we review
      abnormalities in the expression and function of retinoids and their receptors,
      and how they play a critical role in the development of HCC. In particular, a
      malfunction of RXRalpha due to phosphorylation by Ras-MAPK signaling pathway is
      profoundly associated with liver carcinogenesis and thus may be a promising
      target for HCC chemoprevention. Acyclic retinoid (ACR), a synthetic retinoid,
      inhibits Ras-MAPK activation and RXRalpha phosphorylation, thereby suppressing
      growth in HCC-derived cells. In clinical trials, ACR has been shown to improve
      patient survival by preventing viral HCC development, a possible manifestation of
      the concept of "clonal deletion" therapy. "Combination chemoprevention" with ACR
      as the key drug has great potential to become an effective strategy for the
      prevention of liver carcinogenesis. In summary, both basic and clinical research
      strongly suggest that ACR plays a critical role in preventing the development of
      HCC and that "clonal deletion" therapy is one of the most practical approaches
      for this purpose.

PMID- 21196202
TI  - Understanding rituximab function and resistance: implications for tailored
      therapy.
AB  - The addition of anti-CD20 monoclonal antibody (rituximab) to chemotherapy has
      significantly improved survival in B-cell lymphoma. However, a substantial number
      of patients relapse after treatment with rituximab. Understanding of anti-CD20
      antibody molecular function may facilitate the development of pharmacologic
      strategies to overcome resistance. Cell death have been demonstrated to be caused
      by rituximab binding to CD20 throughout direct and indirect mechanisms. The
      direct mechanism comprises growth inhibition, induction of apoptosis and
      sensitization of cells to chemotherapy. While, the indirect mechanisms to
      Rituximab include complement-dependent cytotoxicity (CDC) and antibody-dependent
      cellular cytotoxicity (ADCC). However, these mechanisms are still poorly
      understood. To shed light on this issue, we have analyzed the most significant
      results showing the role of Rituximab as a signal-inducing antibody and as a
      chemosensitizing agent through negative regulation of major survival pathways.
      Mechanisms of resistance to Rituximab are also discussed. Additionally, studies
      here reported show that, cellular targets are modified after treatment with
      Rituximab and may become useful for novel therapeutic strategies in the treatment
      of patients resistant to standard therapy.

PMID- 21196203
TI  - Thyroperoxidase, thyroglobulin, Na(+)/I(-) symporter, pendrin in thyroid
      autoimmunity.
AB  - The autoimmune thyroid diseases (AITD), Graves' disease (GD) and Hashimoto's
      thyroiditis (HT) are most common endocrine disorders in humans. Both disorders
      are characterized by lymphocytic infiltration of the thyroid gland and the
      production of autoantibodies (aAb) against proteins that are thyroid-specific or
      expressed predominantly in the thyroid. The three main autoantigens are
      thyroperoxidase (TPO), thyroglobulin (Tg), and thyrotropin hormone receptor.
      Recently, the thyroidal iodide transporters Na+/I- symporter (NIS) and pendrin
      have also been identified as novel antigens in AITD. TPO-aAb and Tg-aAb are
      hallmarks of AITD, whereas the pathological and clinical relevance of NIS and
      pendrin aAb are still uncertain. To gain a greater understanding of the
      pathogenic mechanism(s) of autoimmune thyroid diseases at the molecular level,
      further characterisation of the autoantigens is required in order to shed light
      on why and how these molecules are seen by the immune system. This review
      summarizes current knowledge regarding the patho-physiological function and
      immunogenic response to the proteins TPO, Tg, NIS, and pendrin.

PMID- 21196204
TI  - In pursuit of new anti-angiogenic therapies for cancer treatment.
AB  - Despite advances in surgery, radiation therapy, and chemotherapy, patients with
      cancer have a poor prognosis. Sustained aberrant tumor angiogenesis and
      metastasis is a major obstacle for effective cancer treatment. Just a few years
      ago, few would argue that one of the key success stories of the modern cancer
      medicine were the anti-angiogenic drugs targeting the vascular endothelial growth
      factor (VEGF) signaling pathway approved by FDA. This initial success inspired
      many researchers to search for new anti-angiogenic targets and drugs with the
      hope that one day, anti-angiogenic therapy might really become the panacea for
      cancer patients. Unfortunately, the limited clinical benefits achieved with anti
      angiogenic drugs conflicts with the widely accepted notion that angiogenesis is a
      key event in tumor progression. Emerging data indicate that unique
      characteristics of the tumor vasculature within the tumor microenvironment may
      hold the key for success of anti-angiogenic therapy. In particular, the molecular
      and cellular alterations that sustain aberrant tumor angiogenesis in the face of
      angiogenic inhibitors represents novel targets for rationally designing and
      improving current anti-angiogenic strategies.

PMID- 21196206
TI  - Acquired endocrine resistance in breast cancer: implications for tumour
      metastasis.
AB  - Endocrine therapy is the treatment of choice in hormone receptor-positive breast
      cancer. However, the effectiveness of these agents is limited by the development
      of drug resistance, ultimately leading to disease progression and patient
      mortality. Whilst pre-clinical cell models of acquired endocrine resistance have
      demonstrated a role for altered growth factor signalling in the development of an
      endocrine insensitive phenotype, it is becoming apparent that acquisition of
      endocrine resistance in breast cancer is also accompanied by the development of
      an adverse cellular phenotype, with resistant cells exhibiting altered adhesive
      interactions, enhanced migratory and invasive behaviour, and a capacity to induce
      angiogenic responses in endothelium. Since invasion and metastasis of cancer
      cells is a major cause of mortality in breast cancer patients, elucidation of
      molecular mechanisms underlying the adverse cellular features that accompany
      acquired endocrine resistance and their subsequent targeting may provide a means
      of limiting the progression of such tumours in vivo.

PMID- 21196207
TI  - Signalling to cancer cell invasion through PAK family kinases.
AB  - Cancer cell metastasis involves a series of changes in cell behaviour, driven by
      oncogenic transformation, that leads to local tissue invasion, migration through
      extracellular matrix, entry into the vascular or lymphatic system and
      colonisation of distant sites. It is well established that the Rho family GTPases
      Rho, Rac and Cdc42 orchestrate many of the processes required during metastasis.
      The Rho family GTPases regulate cellular behaviour through their interaction with
      downstream effector proteins. The p-21 activated kinases (PAKs), effector
      proteins for Rac and Cdc42, are known to be important regulators of cell
      migration and invasion. There are six mammalian PAKs which can be divided into
      two groups: group I PAKs (PAK1-3) and group II PAKs (PAK4-6). Although the two
      PAK groups are architecturally similar there are differences in their mode of
      regulation suggesting their cellular functions are likely to be different. This
      review will focus on the latest evidence relating to the role of PAK family
      kinases in the cell signalling pathways that drive cancer cell migration and
      invasion.

PMID- 21196208
TI  - Bone morphogenetic protein and bone metastasis, implication and therapeutic
      potential.
AB  - Bone metastasis is one of the most common and severe complications in advanced
      malignancies, particularly in the three leading cancers; breast cancer, prostate
      cancer and lung cancer. It is currently incurable and causes severe morbidities,
      including bone pain, hypercalcemia, pathological fracture, spinal cord
      compression and consequent paralysis. However, the mechanisms underlying the
      development of bone metastasis remain largely unknown. Bone morphogenetic
      proteins (BMPs) belong to the TGF-beta superfamily and are pluripotent factors
      involved in the regulation of embryonic development and postnatal homeostasis of
      various organs and tissues, by controlling cellular differentiation,
      proliferation and apoptosis. Since they are potent regulators for bone formation,
      there is an increasing interest to investigate BMPs and their roles in bone
      metastasis. BMPs have been implicated in various neoplasms, at both primary and
      secondary tumors, particularly skeletal metastasis. Recently studies have also
      suggested that BMP signaling and their antagonists play pivotal roles in bone
      metastasis. In this review, we discuss the current knowledge of aberrations of
      BMPs which have been indicated in tumor progression, and particularly in the
      development of bone metastasis.

PMID- 21196205
TI  - Epithelial and mesenchymal phenotypic switchings modulate cell motility in
      metastasis.
AB  - The most ominous stage of cancer progression is metastasis, or the dissemination
      of carcinoma cells from the primary site into distant organs. Metastases are
      often resistant to current extirpative therapies and even the newest biological
      agents cure only a small subset of patients. Therefore a greater understanding of
      tumor biology that integrates properties intrinsic to carcinomas with tissue
      environmental modulators of behavior is needed. In no aspect of tumor progression
      is this more evident than the acquisition of cell motility that is critical for
      both escape from the primary tumor and colonization. In this overview, we discuss
      how this behavior is modified by carcinoma cell phenotypic plasticity that is
      evidenced by reversible switching between epithelial and mesenchymal phenotypes.
      The presence or absence of intercellular adhesions mediate these switches and
      dictate the receptivity towards signals from the extracellular milieu. These
      signals, which include soluble growth factors, cytokines, and extracellular
      matrix embedded with matrikines and matricryptines will be discussed in depth.
      Finally, we will describe a new mode of discerning the balance between
      epithelioid and mesenchymal movement.

PMID- 21196210
TI  - Genetic basis of tumorigenesis in NF1 malignant peripheral nerve sheath tumors.
AB  - Malignant peripheral nerve sheath tumors (MPNSTs), often found associated with
      neurofibromatosis type 1 (NF1), are aggressive tumors that pose significant
      diagnostic and therapeutic challenges. About 10% of NF1 patients may develop an
      MPNST, exhibiting a poor prognosis. With no effective treatment available,
      radical surgery and chemo- and radiotherapy are required to reduce tumor
      recurrence, metastasis and prolong patient survival. MPNST pathogenesis is poorly
      understood due mainly to its complex histopathology, but biallelic NF1 gene
      inactivation is essential for tumor development. There is also no defined
      molecular signature for MPNST development, although several cell-cycle and
      signalling regulation genes (CDKN2A, TP53, RB1, EGFR, CD44, PDGFR, PDGFRA, HGF,
      MET and SOX9) are deregulated. Constitutive activation of several critical cell
      signalling cascades also occurs in MPNSTs and these may define therapeutic
      targets. Both preclinical and clinical trials are proposed, most involving a
      combinatorial therapeutic approach. Multidisciplinary collaborative efforts are
      clearly essential to fully decipher both the complex molecular basis of MPNST
      development and to define potential therapeutic targets.

PMID- 21196209
TI  - Tight junctions in cancer metastasis.
AB  - Tight Junctions (TJ) are well known to function as a control for the paracellular
      diffusion of ions and certain molecules, it has however, become evident that the
      TJ has a vital role in maintaining cell to cell integrity. Loss of cohesion of
      the TJ structure can lead to invasion and ultimately to the metastasis of cancer
      cells. This review will discuss how modulation of expression of TJ molecules
      results in key changes in TJ barrier function leading to the progression of
      cancer and progression of metastasis.

PMID- 21196211
TI  - Investigations of survivin: the past, present and future.
AB  - Survivin is a member of the inhibitors-of-apoptosis protein (IAPs) family. It
      promotes cell survival through interference with multiple cell cycle-related
      proteins such as INCENP and Aurora B kinase. Survivin also inhibits cell death
      through interference with both caspase-dependent and -independent cell apoptosis.
      Interestingly, recent evidence suggests that survivin may also play a role in the
      regulation of cancer cell autophagy. At the clinical level, studies on clinical
      specimens have shown that survivin expression is up-regulated in various human
      cancers and its up-regulation is associated with tumour resistance to both
      chemotherapy and radiation therapy. On the basis of these findings, survivin has
      been proposed as an attractive target for new anti-cancer interventions. However,
      despite the role that survivin plays in cancer cell survival and anti-drug
      response, the development of survivin inhibitors is relatively slow as compared
      to other therapeutic inhibitors for cancer treatment. In this review, the
      relationships between survivin expression and the causation of drug resistance in
      cancers are re-addressed. This review also summarizes the recent development of
      survivin inhibitors for clinical usage.

PMID- 21196212
TI  - The neurobiology of APOE in schizophrenia and mood disorders.
AB  - APOE is a major component of several lipoproteins. In addition to its role as a
      lipid transport protein APOE also serves a dual role as a glial derived, synaptic
      signalling molecule and thought to play an important role in synaptic plasticity
      and cognition. Polymorphisms within the APOE gene have been associated with the
      incidence of Alzheimer's disease. In light of the similarities in the cognitive
      deficits experienced in both Alzheimer's disease and schizophrenia as well as the
      comorbidity of depression in Alzheimer's disease, aberrant APOE signalling has
      been implicated in the pathologies of schizophrenia and mood disorders. The
      schizophrenia candidate gene, reelin, also shares common receptors with APOE,
      further supporting a role for APOE in the pathology of these disorders. This
      review will summarise the current understanding of the involvement of APOE and
      its receptors in the symptomatology and pathology of schizophrenia and mood
      disorders and the implications of this involvement for drug treatment.

PMID- 21196214
TI  - Nanostructures in biosensor--a review.
AB  - In the 21(st) century, it is widely recognized that along with information
      technology (IT) and biotechnology (BT), nanotechnology (NT) will be a key field
      of science that will drive future developments. NT is expected to allow
      innovations in industrial fields such as electrical and electronics,
      biochemistry, environment, energy, as well as materials science by enabling the
      control and operation of materials at the atomic and molecular levels. In
      particular, the application of NT in the field of biochemistry is now enabling
      the realization of previously unachievable objectives.This review discusses the
      growth, synthesis, and biocompatible functionalization of each materials, with an
      emphasis on 1D nanomaterials such as CNTs, inorganic nanowires (made of Si,
      metals, etc.), and conducting polymer nanowires, along with 0D nanomaterials such
      as nanoparticles. This review also investigates the sensing principle and
      features of nanobiosensors made using the abovementioned materials and introduce
      various types of biosensors with nanostructure 0-D and 1-D. Finally, the review
      discusses future research objectives and research directions in the field of
      nanotechnology.

PMID- 21196215
TI  - The c-Fes protein tyrosine kinase as a potential anti-angiogenic target in
      cancer.
AB  - Angiogenesis is implicated in many pathological conditions, including cancer
      progression. Novel approaches have enabled an understanding of how endothelial
      cellular processes are regulated in vivo during angiogenesis. Key players in
      angiogenesis are vascular endothelial growth factors (VEGFs) and Notch ligands.
      However, mechanisms of angiogenic responses by other proangiogenic factors in
      vivo are largely unknown. Research using cultured endothelial cells has shown
      that c-Fes is involved in the activation of phosphoinositide 3-kinase (PI3
      kinase) downstream of a variety of cytokine receptors. The PI3-kinase/c-Akt
      pathway regulates cell survival, migration, and morphological differentiation of
      endothelial cells during angiogenesis, and c-Fes thus may be a potential target
      of anti-cancer therapy, especially for patients with anti-VEGF refractory cancer.
      In addition, a number of experiments have shown that a bone marrow-derived
      monocytic lineage regulates angiogenesis, and c-Fes is also expressed in these
      cells. Roles for c-Fes during angiogenesis will be the focus of extensive
      research in the future.

PMID- 21196213
TI  - Triterpenoids as potential agents for the chemoprevention and therapy of breast
      cancer.
AB  - Breast cancer remains a major cause of death in the United States as well as the
      rest of the world. In view of the limited treatment options for patients with
      advanced breast cancer, preventive and novel therapeutic approaches play an
      important role in combating this disease. The plant-derived triterpenoids,
      commonly used for medicinal purposes in many Asian countries, posses various
      pharmacological properties. A large number of triterpenoids are known to exhibit
      cytotoxicity against a variety of tumor cells as well as anticancer efficacy in
      preclinical animal models. Numerous triterpenoids have been synthesized by
      structural modification of natural compounds. Some of these analogs are
      considered to be the most potent antiinflammatory and anticarcinogenic
      triterpenoids known. This review examines the potential role of natural
      triterpenoids and their derivatives in the chemoprevention and treatment of
      mammary tumors. Both in vitro and in vivo effects of these agents and related
      molecular mechanisms are presented. Potential challenges and future directions
      involved in the advancement of these promising compounds in the prevention and
      therapy of human breast cancer are also identified.

PMID- 21196216
TI  - TS gene tandem repeats in esophageal cancer patients receiving chemoradiotherapy.
AB  - 5-Fluorouracil (5-FU) interferes with tumor-cell proliferation by inhibiting
      thymidylate synthase (TS). We examined the relationship between tandem repeat
      (TR) variations in the TS gene and survival following concurrent
      chemoradiotherapy in patients with esophageal squamous cell carcinoma (ESCC). TS
      TR variations were analyzed in 57 stage II-IV ESCC patients undergoing
      chemoradiotherapy combined with 5-FU and cisplatinum (CDDP), and in 106 controls.
      Pretreatment non-neoplastic biopsy specimens from ESCC patients and lymphocytes
      from controls were used for analysis. Variations were identified by the size of
      DNA fragments amplified by polymerase chain reaction. Two to five TRs were found
      in Japanese individuals. TR3 homozygotes were predominant in 74% of ESCC patients
      and 61% of controls. Three-year survival rates were significantly longer in
      patients with TR2/2 or TR2/3 genotypes (38%) than in patients with TR3/3, 3/4, or
      3/5 genotypes (9%; p=0.011). In the Cox proportional hazard model, the TR2/2 or
      TR2/3 genotypes were the only independent predictor for survival (Hazard ratio,
      2.647; 95% confidence interval, 1.271-5.513). The TS-TR variations exert an
      important influence on survival following chemoradiotherapy in ESCC patients.

PMID- 21196217
TI  - The spinal cord ependymal region: a stem cell niche in the caudal central nervous
      system.
AB  - In the brain, specific signalling pathways localized in highly organized regions
      called niches, allow the persistence of a pool of stem and progenitor cells that
      generate new neurons and glial cells in adulthood. Much less is known on the
      spinal cord central canal niche where a sustained adult neurogenesis is not
      observed. Here we review our current knowledge of this caudal niche in normal and
      pathological situations. Far from being a simple layer of homogenous cells, this
      region is composed of several cell types localized at specific locations,
      expressing characteristic markers and with different morphologies and functions.
      We further report on a screen of online gene-expression databases to better
      define this spinal cord niche. Several genes were found to be preferentially
      expressed within or around the central canal region (Bmp6, CXCR4, Gdf10, Fzd3,
      Mdk, Nrtn, Rbp1, Shh, Sox4, Wnt7a) some of which by specific cellular subtypes.
      In depth characterization of the spinal cord niche constitutes a framework to
      make the most out of this endogenous cell pool in spinal cord disorders.

PMID- 21196218
TI  - Apigenin induces apoptosis and impairs head and neck carcinomas EGFR/ErbB2
      signaling.
AB  - The development of head and neck squamous cell carcinomas (HNSCCs) is a multistep
      process progressing from precancerous lesions to highly malignant tumors. A
      critical role in HNSCCs development and progression is played by EGFR family
      members including EGFR and ErbB2. The aim of this study was to investigate the
      effect of apigenin, a low molecular weight flavonoid contained in fruits and
      vegetables, on growth and survival and on EGFR/ErbB2 signaling in cell lines
      derived from HNSCCs of the tongue (CAL-27, SCC-15) or pharynx (FaDu). Using
      sulforhodamine B assay, FACS analysis and activated caspase-3 detection by
      immunofluorescence, we here demonstrate that apigenin dose-dependently inhibits
      survival and induces apoptosis of HNSCC cells. Further, by performing western
      blotting with antibodies specific for phosphorylated EGFR, ErbB2, Erk1/2 and Akt
      we demonstrate that apigenin reduces ligand-induced phosphorylation of EGFR and
      ErbB2 and impairs their downstream signaling. On the whole, our results suggest
      that apigenin properties might be exploited for chemoprevention and/or therapy of
      head and neck carcinomas.

PMID- 21196219
TI  - The Claudin family and its role in cancer and metastasis.
AB  - Tight Junctions are the most apical element of the junctional complex in
      epithelial and endothelial cells. Tight Junctions form a barrier to paracellular
      movement of substances separating the apical and basolateral fluid compartments
      on opposite sides of the epithelial cell layer. The Claudin family are Tight
      Junction proteins expressed in both endothelial and epithelial cells. They
      participate in the development of tissue barriers between different tissue
      compartments by regulating the efflux of molecules through Tight Junction
      complexes. At least 24 different Claudin members are known today, all of which
      are thought to vary in expression depending on location and cell type. Relatively
      little is know about Claudins and their role in carcinogenesis and progression to
      metastasis. Recently, this new area of research has become very promising as a
      result of the frequent existence of altered Claudin expression in cancer. That
      Claudins are pivotal in the maintenance of Tight Junctions function begs
      investigation into the changes that can occur during the metastatic process.

PMID- 21196220
TI  - Nanomaterials for biosensing with electrochemiluminescence (ECL) detection.
AB  - Analytical applications of nanomaterials used in electrochemiluminescence (ECL)
      based detection methods are reviewed. Among nanomaterials, carbon-based
      nanomaterials (carbon nanotubes, graphene), metal nanoparticles, quantum dots,
      inorganic metal complexes and conducting polymers are considered. The most common
      mechanisms of ECL detections are also described in this review. Finally,
      challenges and perspectives of the use of such materials in chemical analysis are
      discussed.

PMID- 21196222
TI  - Mechanisms of oxidative DNA damage induced by carcinogenic arylamines.
AB  - Most arylamines are pro-carcinogens, and require metabolic activation to yield
      ultimate carcinogen metabolites. O-Acetylation of the N-hydroxy form of an
      arylamine yields an acetoxyarylamine, which can form a highly reactive
      arylnitrenium ion, the ultimate metabolite responsible for DNA adduct formation.
      However, we demonstrate here that the N-hydroxy and nitroso forms of arylamines
      can also induce DNA damage, including 7,8-dihydro-8-oxo-2'-deoxyguanosine (8
      oxodG) lesions, via reactive oxygen species formation. The N-hydroxy and nitroso
      derivatives of carcinogenic arylamines may contribute to the carcinogenic process
      through H2O2 formation. N-Hydroxy derivatives induce metal-mediated DNA damage,
      with remarkable enhancement by NADH. Nitroso derivatives induce NADH-dependent
      DNA damage in the presence of metal ions. Hydroxy derivatives of arylamines
      formed by enzymatic hydroxylation or as o- or p-aminophenols can also induce DNA
      damage in the presence of metal ions. The autoxidation of o-phenylenediamine and
      several arylamine metabolites is accelerated in the presence of SOD or manganese,
      resulting in the enhancement of metal-mediated DNA damage. The oxidative DNA
      damage induced by arylamine compounds may participate in chemical carcinogenesis,
      in addition to DNA adduct formation.

PMID- 21196223
TI  - Regulation of MDM4.
AB  - Mouse double minute 4 (MDM4), also known as MDMX or HDMX (human MDMX), is a
      critical negative regulator of the tumor suppressor p53. Under normal growth
      conditions, MDM4 contributes to the repression of p53 activity. Upon DNA damage,
      it becomes important to down-regulate MDM4 to allow a full p53 response. Here,
      the mechanisms by which MDM4 activity is controlled are reviewed and discussed,
      starting with alterations in copy number, then control of transcription, mRNA
      stability, translation, and finally post-translational interactions,
      modifications, localization, and targeting by recently developed drugs.

PMID- 21196224
TI  - Antigen presentation in EAE: role of microglia, macrophages and dendritic cells.
AB  - Experimental autoimmune encephalomyelitis (EAE), a well-established model of
      multiple sclerosis, is characterised by microglial activation and lymphocytic
      infiltration. Lymphocytic activation through the antigen presentation process
      involves three main signals, the first provided by the engagement of major
      histocompatibility complex molecules (MHC) with the receptor of T-cells (TCR),
      the second by the binding of co-stimulatory molecules and the third by the
      secretion or expression of T-cell polarising molecules in specific populations of
      antigen presenting cells (APC). Microglial cells are considered to be the main
      APC population in the central nervous system (CNS). Specifically in EAE an
      increase in MHCs, co-stimulatory molecules and different T-cell polarising
      factors have been reported in microglia. However, a growing number of evidences
      suggest that dendritic cells (DCs), the main APC in the peripheral immune system,
      may also participate in the regulation of T-cell responses within the CNS. In
      this review we summarize the principal knowledge regarding microglial/macrophage
      function in EAE and their role in T-cell modulation, as well as the participation
      of DCs in the immune response associated to this disease.

PMID- 21196221
TI  - Myb proteins: angels and demons in normal and transformed cells.
AB  - A key regulator of proliferation, differentiation and cell fate, the c-Myb
      transcription factor regulates the expression of hundreds of genes and is in turn
      regulated by numerous pathways and protein interactions. However, the most unique
      feature of c-Myb is that it can be converted into an oncogenic transforming
      protein through a few mutations that completely change its activity and
      specificity. The c-Myb protein is a myriad of interactions and activities rolled
      up in a protein that controls proliferation and differentiation in many different
      cell types. Here we discuss the background and recent progress that have led to a
      better understanding of this complex protein, and outline the questions that have
      yet to be answered.

PMID- 21196226
TI  - Alpha-Ketoglutarate and intestinal function.
AB  - Alpha-ketoglutarate (AKG) is an intermediate of the Krebs cycle which bridges
      amino acid metabolism with glucose oxidation in animals. Of particular interest
      is the conversion of AKG into glutamate by mitochondrial glutamate dehydrogenase
      in the gastrointestinal tract where glutamate has multiple physiological
      functions (including regulation of cell function, neurotransmission, and gastric
      emptying). Additionally, AKG stimulates the initiation of catabolism of branched
      chain amino acids (BCAA) via BCAA transaminase in enterocytes. Oxidation of AKG
      also provides large amounts of ATP and modulates cellular redox state in the
      small intestine. Translating the basic research into practice, results of recent
      studies indicate that dietary supplementation with AKG alleviates oxidative
      stress and injury in intestinal mucosal cells, while improving intestinal mucosal
      integrity and absorption of nutrients in endotoxin-challenged pigs. The
      beneficial effects of AKG are associated with increased activation of the mTOR
      signaling pathway and net protein synthesis. Thus, AKG is a novel and promising
      supplement in diets to improve intestinal health in animals and possibly humans.

PMID- 21196227
TI  - Regulation of resident and newcomer insulin granules by calcium and SNARE
      proteins.
AB  - Insulin, stored in large dense core granules, is biphasically exocytosed by
      glucose stimulation in pancreatic beta-cells. Several molecules, such as SNARE
      proteins, and Ca2+ ion are involved in the regulation of insulin exocytosis.
      Indeed, studies using gene targeting mice revealed critical roles of SNARE
      proteins and their accessory proteins, which may be associated with diabetes
      mellitus. In particular, the total internal reflection fluorescent (TIRF) imaging
      technique shed new light on the molecular mechanism of the insulin exocytotic
      process. In this review we discuss the mechanism of insulin exocytosis mainly
      from a point of view of imaging techniques.

PMID- 21196228
TI  - Fragile X syndrome: from gene discovery to therapy.
AB  - A dynamic mutation in the fragile X mental retardation 1 gene, FMR1, was found to
      cause fragile X syndrome almost 20 years ago. Since, a wealth of information
      regarding the function of the gene has been gathered. It plays a role in RNA
      transport and stability and RNA-binding influences the function of a multitude of
      other genes. In this review, we focus on the recent knowledge of molecular and
      biochemical pathways shown to be relevant in the fragile X syndrome and how these
      insights have led to a first series of clinical trials in fragile X patients.

PMID- 21196225
TI  - NF-kappaB in lung cancer, a carcinogenesis mediator and a prevention and therapy
      target.
AB  - Lung cancer ranks as the first malignant tumor killer worldwide. Despite the
      knowledge that carcinogens from tobacco smoke and the environment constitute the
      main causes of lung cancer, the mechanisms for lung carcinogenesis are still
      elusive. Cancer development and progression depend on the balance between cell
      survival and death signals. Common cell survival signaling pathways are activated
      by carcinogens as well as by inflammatory cytokines, which contribute
      substantially to cancer development. As a major cell survival signal, nuclear
      factor-kappaB (NF-kappaB) is involved in multiple steps in carcinogenesis and in
      cancer cell's resistance to chemo- and radio-therapy. Recent studies with animal
      models and cell culture systems have established the links between NF-kappaB and
      lung carcinogenesis, highlighting the significance of targeting NF-kappa
      signaling pathway for lung cancer treatment and chemoprevention. In this review,
      we summarize progresses in understanding the NF-kappaB pathway in lung cancer
      development as well as in modulating NF-kappaB for lung cancer prevention and
      therapy.

PMID- 21196229
TI  - Brown fat biology and thermogenesis.
AB  - Brown fat (brown adipose tissue, BAT) primary function is to produce heat. There
      is now compelling evidence to indicate that brown fat cells in some BAT depots
      share their predecessor cells with myocytes. Brown adipocyte
      (trans)differentiation depends on various receptors / transcription factors that
      include peroxisome proliferator-activated receptor g (PPARgamma), PPARgamma
      coactivator-1alpha (PGC1alpha), PRD1-BF1-RIZ1 homologous domain-containing 16
      (PRDM16), CCAAT/enhancer-binding protein beta (C/EBP-beta) and bone morphogenetic
      protein 7 (BMP7). Such mediators also help BAT to acquire its thermogenic
      phenotype, which is essentially conferred by uncoupling protein 1 (UCP1). UCP1
      uncouples adenosine-5'-triphosphate (ATP) synthesis from substrate oxidation in
      brown adipocytes. Its activity depends on the availability of fatty acids
      delivered upon BAT's beta)-adrenergic activation, which, physiologically, ensues
      from the sympathetic nervous system (SNS) activation of the tissue. SNS-mediated
      thermogenesis is largely controlled by the hypothalamus and brainstem. Recently,
      positron emission tomography / computed tomography (PET/CT) scanning
      investigations have revealed the presence in adult humans of important neck and
      shoulder BAT depots. That finding has contributed to reinstate a strong interest
      for brown adipocyte biology and thermogenesis. This review aims at the unique
      biology of BAT with the emphasis put on the recent discoveries regarding the
      brown adipocyte development and function.

PMID- 21196230
TI  - From sequence to structural analysis in protein phosphorylation motifs.
AB  - Phosphorylation is the most widely studied post-translational modification
      occurring in cells. While mass spectrometry-based proteomics experiments are
      uncovering thousands of novel in vivo phosphorylation sites, the identification
      of kinase specificity rules still remains a relatively slow and often
      inefficacious task. In the last twenty years, many efforts have being devoted to
      the experimental and computational identification of sequence and structural
      motifs encoding kinase-substrate interaction key residues and the phosphorylated
      amino acid itself. In this review, we retrace the road to the discovery of
      phosphorylation sequence motifs, examine the progresses achieved in the detection
      of three-dimensional motifs and discuss their importance in the understanding of
      regulation and de-regulation of many cellular processes.

PMID- 21196231
TI  - Theoretical and computational approaches to ligand-based drug discovery.
AB  - The basic idea behind ligand-based approaches is that the analysis of sets of
      molecules with experimentally determined activities can highlight those chemical
      features responsible for the activity changes. Historically, such approaches have
      been devised before structure-based methods. Nowadays, despite the ever
      increasing availability of experimentally determined structures, ligand-based
      approaches still play a major role in drug design either alone or in conjunction
      with structure-based efforts. This manuscript aims to provide a general overview
      of the main computational approaches in ligand-based drug discovery, particularly
      3D QSAR methods, along with relevant references to the literature.

PMID- 21196232
TI  - DNA damage and repair in age-related macular degeneration.
AB  - Oxidative stress may play an important role in the pathogenesis of age-related
      macular degeneration (AMD). Mitochondria produce reactive oxygen species (ROS),
      which induce degenerative changes typical for AMD. Mitochondrial DNA (mtDNA) is
      targeted by ROS and it is considered to be more vulnerable to damage than nuclear
      DNA (nDNA) due to the impaired DNA repair system, lack of nucleosomal
      organization and close vicinity of mitochondrial oxidative chain. Some reports
      suggest the association between mtDNA damage and AMD. However, the metabolism of
      mtDNA is mainly determined by the expression of nDNA. Therefore, the extent of
      damage to mtDNA in retinal cells depends on the overall efficacy of nDNA repair,
      which decreases with age. We showed an association between nDNA damage and repair
      and AMD. Also well-recognized factors of AMD pathogenesis, age and smoking, may
      exert their effects through the DNA damage and repair. In conclusion, DNA damage
      and repair, both in mitochondrial and nuclear genome, may play an important role
      in the pathogenesis of AMD, and their mutual relationship in this disease needs
      further study.

PMID- 21196233
TI  - Signalling pathways and vascular calcification.
AB  - Vascular calcification is a major risk factor for cardiovascular morbidity and
      mortality. A full understanding of the signalling pathways mediating vascular
      calcification is crucial not just because of the importance of this pathology in
      disease, but also for exploring potential therapeutic targets. Clinically there
      is a need to develop therapies to prevent or even reverse calcification in
      situations of atherosclerosis, chronic kidney disease, diabetes, and aging. In
      this brief review, we intend to explore the initial triggers, which are commonly
      related to calcification in different disease scenarios and examine the
      downstream signalling pathways that instigate the process of vascular
      calcification. In particular, we try to dissect these pathways and also examine
      cross-talk between different signalling pathways. Our focus is the vascular
      smooth muscle cell (VSMC) as it is ultimately the phenotypic modulation of these
      cells that may drive the calcification process.

PMID- 21196234
TI  - Role of a-kinase anchoring proteins (AKAPs) in reproduction.
AB  - Rapid spatio-temporal organized intracellular signaling is a pivotal mechanism
      for regulation of functions in many cells, in particular in the female and male
      gametes, in which functional regulation through rapid increases in protein
      content is not possible since the mechanisms of transcription/translation are
      somehow frozen due to meiosis block or DNA condensation respectively. A kinase
      anchoring proteins (AKAPs) represent a functional conserved family of signal
      organizing scaffolding proteins, which due to the specific subcellular
      distribution and focally compartmentalized cyclic-AMP-dependent protein kinase
      (PKA) and other enzymes, assuring the coordination of cAMP-responsive events and
      their integration with other intracellular signals. This review summarizes the
      actual knowledge on AKAP structure and functions, taking into particular account
      the role of different AKAPs in regulating reproductive functions such as
      gametogenesis. Evidence for sperm specific AKAP isoforms and their initiated
      signaling cascades in mature sperm and the role of this focally activated super
      molecular signaling complex in motility are discussed in details with particular
      emphasis on putative relations between AKAP structural and functional alterations
      and defects in sperm motility.

PMID- 21196235
TI  - Channelling of arginine in NO and polyamine pathways in colonocytes and
      consequences.
AB  - Colon epithelium is renewed within few days through asymmetric mitosis of
      pluripotent cells followed by differentiation and exfoliation. Absorptive
      colonocytes do not transport amino acids from lumen to bloodstream but import
      amino acids from plasma. Among amino acids, colonocytes can use L-arginine as a
      precursor for nitric oxide (NO) synthesis and also for polyamine synthesis
      through the stepwise conversion of L-arginine into L-ornithine and urea,
      conversion of L-ornithine into putrescine and then synthesis of spermidine and
      spermine. Colonic epithelial cells can transport polyamines produced exogenously
      by the microbiota. Polyamines are strictly necessary for undifferentiated colonic
      epithelial cell proliferation but NO exerts anti-proliferative effect on these
      cells raising the view that the channelling of arginine in the nitric oxide and
      polyamine pathways is involved in the control of cellular proliferation.
      Furthermore, NO has been shown to be a potent inhibitor of ornithine
      decarboxylase activity in colonic epithelial cells. Unbalance of the chanelling
      of arginine in the NO and polyamine pathways in colonic cancerous epithelial
      cells as a determinant promoting their proliferation is discussed.

PMID- 21196236
TI  - Markers of human sperm functions in the ICSI era.
AB  - The process of fertilization is crucial for species development and maintenance.
      Due to social and environmental problems, the number of infertile couples is
      increasing worldwide. Male and female factors contribute equally, and about 7% of
      men experiences problems in conceiving a child due to sperm defects. Assisted
      reproduction techniques (ARTs), including the most invasive intracytoplasmic
      sperm injection (ICSI), are the only available therapy for severe male factor
      infertility. Whether such techniques are associated with increased birth defects
      is still debated, and search for alternative options should go on. A better
      understanding of the molecular mechanisms involved in the process of
      fertilization may lead to the development of new pharmacological strategies to
      treat infertile men and new male contraceptive agents. In addition, in view of
      the low predictive power of routine semen analysis, new tests aimed to better
      predict the fertilization potential could be developed. The present review
      summarizes current evidence of the molecular mechanisms involved in fertilization
      in human spermatozoa, with particular emphasis on the main post-ejaculatory
      maturation events, i.e. sperm capacitation and motility.

PMID- 21196237
TI  - Risk factors and metabolic mechanisms in the pathogenesis of uraemic cardiac
      disease.
AB  - Chronic kidney disease has been increasingly recognized as a risk factor for
      incident heart failure. Despite advances in chronic heart failure treatment, the
      prognosis remains poor. The annual mortality from all cardiovascular causes in
      the end stage renal disease population is significantly higher than the general
      population, accounting for more than half of all deaths in this group. The
      mechanisms underlying the enhanced susceptibility to myocardial ischemia in
      chronic kidney disease are not well defined. Traditional cardiovascular risk
      factors, although common in chronic kidney disease, do not exert the same impact
      as in the general population. The presence of "renal-specific" non-traditional
      risk factors including endothelial dysfunction, inflammation, oxidative stress,
      anaemia, proteinuria and changes in vitamin D metabolism (encompassing the
      complex interactions of calcium and phosphate metabolism, hyperparathyroidism and
      vascular calcification) play an important role in cardiovascular disease
      progression. An increased understanding of the array of metabolic
      changes/adaptations occurring in uraemic heart disease have allowed one to
      consider optimal management strategies and to develop new strategies for future
      management of uraemic heart disease.

PMID- 21196238
TI  - Recent developments in lipid-based pharmaceutical nanocarriers.
AB  - Within the broad spectrum of nanoparticulate carriers, polymeric and lipid-core
      micelles, liposomes, solid nanoparticles and many others have demonstrated great
      biological properties which make them excellent pharmaceutical delivery systems.
      In particular, micelles and liposomes have been shown to have good longevity in
      the blood that allows their accumulation in pathological areas with a compromised
      vasculature; can possess specific targeting to disease sites when various
      targeting ligands are attached to the surface of the nanocarriers or to surface
      attached cell-penetrating molecules (like TAT peptide) to enhance intracellular
      penetration; possess stimulus-sensitivity allowing for drug release from the
      carriers under certain pathological conditions; and show contrast properties with
      carrier loading of various contrast materials that allow for direct carrier
      visualization in vivo. The engineering of "multifunctional pharmaceutical
      nanocarriers" based on the combination of several useful properties in the same
      system can significantly enhance the efficacy of many therapeutic and diagnostic
      protocols. This review considers the current status and next future directions in
      the emerging area of nanomedicine with particular attention to two lipid-based
      nanoparticulate systems: liposomes and micelles.

PMID- 21196239
TI  - Vasculogenensis, angiogenesis and special features of tumor blood vessels.
AB  - The circulatory system comprises a tubular network of blood vessels including
      arterioles, capillaries, venules, and lymphatic vessels. This circulatory system
      is essential for the embryonic development and maintenance of all tissues, which
      requires the transportation of oxygen, carbon dioxide, and nutrition. The system
      regulates the movement of fluid into and out of organs with high level of
      efficiency. "Tumor angiogenesis" describes the rapid growth of certain components
      of the circulatory system in an abnormal fashion that is both heterogeneous and
      dysregulated. The aberrant flow between abnormal tumor vessels and normal vessels
      poses a high risk for seeding of potentially metastatic cancer cells. Moreover,
      it has also been reported that premetastatic distant organ vessels already
      undergo specific changes due to the presence of a remote primary tumor.
      Therapeutic strategies aimed at targeting tumor vessels have the potential to
      suppress tumor growth, and also influence the effects of tumor-derived cytokines
      and circulating tumor cells. Furthermore, focusing on vessels in a premetastatic
      organ that have responded to a primary tumor may be one possibility for reducing
      metastatic risk.

PMID- 21196240
TI  - Behavioral thermoregulation in mammals: a review.
AB  - In mammals, thermoregulation is a key feature in the maintenance of homeostasis.
      Thermoregulatory capacities are strongly related to energy balance and animals
      are constantly seeking to limit the energy costs of normothermia. In case of
      thermal changes, physiological mechanisms are enhanced, increasing rates of
      energy expenditure. However, behavioral adjustments are available for species to
      lower the autonomic work, and thus reduce the energy costs of thermoregulatory
      responses. Hence, thermogenesis-induced metabolic costs can be reduced during
      cold exposure, and hyperthermia associated to dehydration can be avoided during
      heat exposure. Hypothermia avoidance consists in a concomitant decrease in heat
      dissipation and increase in heat production. Inversely, heat exchange is enhanced
      and body heat production is reduced when avoiding hyperthermia. The different
      behavioral strategies available for mammal species to cope with both decreased
      and increased levels of ambient temperature are reviewed. Moreover,
      thermoregulation function is under the control of central, metabolic, energetic
      and endocrine systems, which induces that parameters such as hour of the day,
      season, gender or aging may affect thermoregulatory adjustments. Some examples
      will be given.

PMID- 21196242
TI  - Contribution of PKB/AKT signaling to thyroid cancer.
AB  - The family of serine/threonine kinases B/Akt (hereafter Akt) represents a central
      node in signalling pathways downstream of growth factors, cytokines, and other
      cellular stimuli. In mammalian cells the Akt family comprises three highly
      homologous members -known as Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma- that
      regulate several processes including cell proliferation and survival, growth and
      response to nutrient availability, migration, tissue invasion and angiogenesis.
      Aberrant activation of Akt is involved in a variety of human cancers including
      those arising in the thyroid gland. Here, we review the contribution of Akt
      dependent pathway in the proliferation of normal thyrocytes, the different
      pathogenic mechanisms underlying aberrant Akt signalling in thyroid malignancies
      as well as the relative roles of Akt substrates that most likely contribute to
      the onset and/or progression of thyroid cancer. Finally, we discuss the current
      therapeutic strategies targeting the components of the PI3K/Akt pathway in the
      context of thyroid malignancy.

PMID- 21196243
TI  - In vitro generation of immune cells from pluripotent stem cells.
AB  - Stem cell transplant recipients and acquired or inherited immune-deficiency
      patients could benefit from the infusion of B, T and/or NK cells. These lymphoid
      cells can be generated in vitro from bone marrow derived CD34+CD45+ hematopoietic
      stem cells (HSC). The number of cells that can be obtained in this way is limited
      especially in the adult. An alternative source may therefore constitute human
      pluripotent stem cells (PSC) such as embryonic (hESC) or induced pluripotent stem
      cells (hiPSC). Here, we focus on present knowledge on the generation of lymphoid
      cells from hESC. The two main obstacles for the generation of clinically relevant
      immune cells are the failure to generate from hESC long-term repopulating HSC
      which could be kept in culture for prolonged time; and insufficient knowledge of
      the selection process which generates mature T cells from CD4 CD8 double positive
      (DP) precursors in vitro.

PMID- 21196241
TI  - Regulation of protein synthesis by amino acids in muscle of neonates.
AB  - The marked increase in skeletal muscle mass during the neonatal period is largely
      due to a high rate of postprandial protein synthesis that is modulated by an
      enhanced sensitivity to insulin and amino acids. The amino acid signaling pathway
      leading to the stimulation of protein synthesis has not been fully elucidated.
      Among the amino acids, leucine is considered to be a principal anabolic agent
      that regulates protein synthesis. mTORC1, which controls protein synthesis, has
      been implicated as a target for leucine. Until recently, there have been few
      studies exploring the role of amino acids in enhancing muscle protein synthesis
      in vivo. In this review, we discuss amino acid-induced protein synthesis in
      muscle in the neonate, focusing on current knowledge of the role of amino acids
      in the activation of mTORC1 leading to mRNA translation. The role of the amino
      acid transporters, SNAT2, LAT1, and PAT, in the modulation of mTORC1 activation
      and the role of amino acids in the activation of putative regulators of mTORC1,
      i.e., raptor, Rheb, MAP4K3, Vps34, and Rag GTPases, are discussed.

PMID- 21196244
TI  - Biological properties of the PrP-like Shadoo protein.
AB  - The SPRN gene encodes the Shadoo glycoprotein (Sho), a central nervous system
      expressed member of the prion protein superfamily. Sho has similarity to two
      features within PrPC's natively unstructured N-terminus, a hydrophobic domain and
      tandem repeats with positively charged residues. Indeed, scrutiny of Sho's
      biochemical properties in uninfected cells has revealed overlaps with the
      properties of PrPC, these including shared protein binding partners. SPRN is
      conserved in mammals, as is the prion gene PRNP, but in sheep SPRN and PRNP are
      both marked by polymorphic variation, suggestive of a shared selection pressure
      within these scrapie disease-prone livestock animals. In rodent models of prion
      disease there are reduced levels of Sho in infected tissues, defining a form of
      cross-regulation between full-length Sho holoprotein and PrPSc. In human prion
      disease an SPRN signal peptide polymorphism is associated with risk for sporadic
      Creutzfeldt-Jakob Disease (CJD), while two patients with early-onset variant CJD
      carried putatively inactive SPRN alleles. Further investigation of Sho as a novel
      tracer or modifier for the accumulation of pathologic forms of PrP may prove
      advantageous.

PMID- 21196245
TI  - Proliferation unleashed: the role of Skp2 in vascular smooth muscle cell
      proliferation.
AB  - Vascular smooth muscle cell proliferation plays a major role in the development
      of numerous vascular pathologies. Understanding the molecular mechanisms that
      regulate smooth muscle cell proliferation is therefore essential for the
      development of new therapies for the treatment of these pathologies. Skp2 is an F
      box protein component of the SCFSkp2 ubiquitin-ligase that controls cellular
      proliferation by regulating the ubiquitination and degradation of several cell
      cycle regulatory proteins, including the cyclin-dependent kinase inhibitor,
      p27Kip1. This review discusses the recent literature on the function and
      regulation of Skp2 in smooth muscle cells, which is emerging as a key player in
      the control of smooth muscle cell proliferation during vascular disease.

PMID- 21196246
TI  - The FERM family proteins in cancer invasion and metastasis.
AB  - Metastasis is the major cause of death in patients with cancer. Metastatic cancer
      cells undergo dramatic molecular and cellular changes by remodeling their cell
      cell and cell-matrix adhesion and their actin cytoskeleton, molecular processes
      that involve the activity of various signaling networks. The FERM family proteins
      can link transmembrane proteins to the cytoskeleton or link kinase and/or
      phosphatase enzymatic activity to the plasma membrane. They thus are involved not
      only in cell-extracellular matrix interactions and cell-cell communication but
      also in apoptosis, carcinogenesis and metastasis. This review will summarize the
      role and mechanism of FERM proteins, with particular reference to the ERM and
      Ehm2 proteins in cancer metastasis.

PMID- 21196247
TI  - Implications of altered iron homeostasis for age-related macular degeneration.
AB  - Reactive oxygen species (ROS) may contribute to the pathogenesis of age-related
      macular degeneration (AMD) and they can be produced in the Fenton reaction
      catalyzed by Fe3+ ions. Therefore, altered homeostasis of iron in the retina may
      be the source of ROS and its damage resulting in clinically detectable AMD
      symptoms. The results of some post mortem research indicate a higher
      concentration of iron in AMD retinas in comparison with non-affected retinas,
      although those results do not determine whether iron overload is the reason or a
      consequence of AMD. However, the results of some other research suggest that iron
      may contribute to the pathogenesis of AMD. Those include increasing of macular
      iron level with age, involvement of iron in the pathogenesis of some degenerative
      diseases linked with AMD, upregulation of transferrin in AMD, developing of AMD
      like syndromes in mice deficient in ceruloplasmin and hephaestin, association
      between polymorphism of the iron homeostasis genes and AMD and others. Better
      understanding of the role of altered iron homeostasis may be useful in prevention
      and curing of AMD.

PMID- 21196250
TI  - Brown adipose tissue growth and development: significance and nutritional
      regulation.
AB  - The last decade has witnessed a profound resurgence in brown adipose tissue (BAT)
      research. The need for such a dramatic increase stems from the ever-growing trend
      toward global obesity. Indeed, it is currently estimated that rates of obesity in
      developed countries such as the United States exceed 35% of the population (1).
      The higher incidence of obesity is associated with increased prevalence of the
      metabolic syndrome including diabetes, hypertension, and coronary heart disease,
      among others (1, 2). BAT holds great promise in combating obesity given its
      unprecedented metabolic capacity. Leading the way has been recent studies, which
      conclusively demonstrate significant quantities of functional BAT in adult humans
      (3-7). These findings have been complimented by elegant studies elucidating the
      developmental origin of the brown adipocyte and the transcriptional regulation
      involved in its differentiation. This review will attempt to meld the wealth of
      new information regarding BAT development with established literature to provide
      an up to date synopsis of what is known and thus a framework for future research
      directions.

PMID- 21196249
TI  - Targeting the anthrax receptors, TEM-8 and CMG-2, for anti-angiogenic therapy.
AB  - The anthrax toxin receptors tumor endothelial marker-8 (TEM-8) and capillary
      morphogenesis gene-2 (CMG-2) are responsible for allowing entry of anthrax toxin
      into host cells. These receptors were first discovered due to their enhanced
      expression on endothelial cells undergoing blood vessel growth or angiogenesis in
      model systems. Inhibition of angiogenesis is an important strategy for current
      anti-cancer therapies and treatment of retinal diseases. Functional roles for TEM
      8 and CMG-2 in angiogenesis have recently emerged. TEM-8 appears to regulate
      endothelial cell migration and tubule formation whereas a role for CMG-2 in
      endothelial proliferation has been documented. TEM-8 and CMG-2 bind
      differentially to extracellular matrix proteins including collagen I, collagen IV
      and laminin and these properties may be responsible for their apparent roles in
      regulating endothelial cell behavior during angiogenesis. TEM-8-binding moieties
      have also been suggested to be useful in selectively targeting anti-angiogenic
      and anti-tumorigenic therapies to tumor endothelium. Additionally, studies of
      modified forms of lethal toxin (LeTx) have demonstrated that targeted inhibition
      of MAPKs within tumor vessels may represent an efficacious anti-angiogenic
      strategy.

PMID- 21196248
TI  - Physiological consequences of membrane-initiated estrogen signaling in the brain.
AB  - Many of the actions of 17beta-estradiol (E2) in the central nervous system (CNS)
      are mediated via the classical nuclear steroid receptors, ER(alpha) and ERbeta,
      which interact with the estrogen response element to modulate gene expression. In
      addition to the nuclear-initiated estrogen signaling, E2 signaling in the brain
      can occur rapidly within minutes prior to any sufficient effects on transcription
      of relevant genes. These rapid, membrane-initiated E2 signaling mechanisms have
      now been characterized in many brain regions, most importantly in neurons of the
      hypothalamus and hippocampus. Furthermore, our understanding of the physiological
      effects of membrane-initiated pathways is now a major field of interest in the
      hypothalamic control of reproduction, energy balance, thermoregulation and other
      homeostatic functions as well as the effects of E2 on physiological and
      pathophysiological functions of the hippocampus. Membrane signaling pathways
      impact neuronal excitability, signal transduction, cell death, neurotransmitter
      release and gene expression. This review will summarize recent findings on
      membrane-initiated E2 signaling in the hypothalamus and hippocampus and its
      contribution to the control of physiological and behavioral functions.

PMID- 21196251
TI  - Role of cereal type and processing in whole grain in vivo protection from
      oxidative stress.
AB  - The reduced risk of chronic diseases related to whole grain consumption is in
      part attributed to their high antioxidant content. Many studies have been
      performed on the in vitro antioxidant capacity of cereals, but in vivo studies
      are necessary. We have evaluated and compared the effect of whole grain durum
      wheat bread and whole grain Kamut khorasan bread on the oxidative status in rats.
      Two different bread-making processes were used for whole grain Kamut khorasan,
      sourdough and baker's yeast. After 7 weeks on the experimental diets rats were
      divided into two subgroups, one receiving an oxidative stress by doxorubicin
      injection. Our results evidenced both wheat durum and Kamut khorasan as good
      sources of antioxidants, and a lower oxidative state in rats fed the cereal-based
      diets. Furthermore, Kamut khorasan bread fed animals had a better response to
      stress than wheat durum fed, especially when a sourdough bread was supplied.
      Although further studies are needed, data herein reported suggest whole grains,
      particularly whole ancient grains, as a safe and convenient way of increasing
      antioxidant protection.

PMID- 21196252
TI  - Bridging quantum mechanics and structure-based drug design.
AB  - The last decade has seen great advances in the use of quantum mechanics (QM) to
      solve biological problems of pharmaceutical relevance. For instance, enzymatic
      catalysis is often investigated by means of the so-called QM/MM approach, which
      uses QM and molecular mechanics (MM) methods to determine the (free) energy
      landscape of the enzymatic reaction mechanism. Here, I will discuss a few
      representative examples of QM and QM/MM studies of important metalloenzymes of
      pharmaceutical interest (i.e. metallophosphatases and metallo-beta-lactamases).
      This review article aims to show how QM-based methods can be used to elucidate
      ligand-receptor interactions. The challenge is then to exploit this knowledge for
      the structure-based design of new and potent inhibitors, such as transition state
      (TS) analogues that resemble the structure and physicochemical properties of the
      enzymatic TS. Given the results and potential expressed to date by QM-based
      methods in studying biological problems, the application of QM in structure-based
      drug design will likely increase, making of these once-prohibitive computations a
      routinely used tool for drug design.

PMID- 21196253
TI  - Associations between adipokines and obesity-related cancer.
AB  - There is increasing evidence that obesity may have pathophysiological effects
      that extend beyond its well-known co-morbidities; in particular its role in
      cancer has received considerable epidemiological support. As adipose tissue
      becomes strongly established as an endocrine organ, two of its most abundant and
      most investigated adipokines, leptin and adiponectin, are also taken beyond their
      traditional roles in energy homeostasis, and are implicated as mediators of the
      effects of obesity on cancer development. This review examines these adipokines
      in relation to the prostate, breast, colorectal, thyroid, renal, pancreatic,
      endometrial and oesophageal cancers, and how they may orchestrate the influence
      of obesity on the development of these malignancies.

PMID- 21196255
TI  - Inflammatory markers and cardiovascular risk in the metabolic syndrome.
AB  - Elevated blood glucose, obesity, high blood pressure, elevated triglycerides and
      low high density lipoprotein (HDL) cholesterol are well accepted risk factors in
      the development of coronary artery disease. Clustering of at least three of these
      factors in an individual is defined as metabolic syndrome (MetS). Obesity is a
      central pathological mechanism in the disease and it is expected that the
      incidence of this condition will increase dramatically within the next years. The
      visceral adipose tissue is not only an energy depot but also an endocrine organ
      which produces a large number of bioactive molecules, the so called adipokines.
      In the setting of obesity, the over-production of proinflammatory and pro
      thrombotic adipokines is associated with insulin resistance. This mechanism
      represents the pathophysiological basis for the development of MetS. Inflammation
      has a central role in the pathogenesis of MetS and in mediating its impact on the
      development of cardiovascular disease. Knowledge of these mechanisms has
      relevance in the context of preventive and therapeutic strategies.

PMID- 21196254
TI  - Colon cancer stem cells: implications in carcinogenesis.
AB  - The cancer stem cell model was described for hematologic malignancies in 1997 and
      since then evidence has emerged to support it for many solid tumors as well,
      including colon cancer. This model proposes that certain cells within the tumor
      mass are pluripotent and capable of self-renewal and have an enhanced ability to
      initiate distant metastasis. The cancer stem cell model has important
      implications for cancer treatment, since most current therapies target actively
      proliferating cells and may not be effective against the cancer stem cells that
      are responsible for recurrence. In recent years great progress has been made in
      identifying markers of both normal and malignant colon stem cells. Proteins
      proposed as colon cancer stem cell markers include CD133, CD44, CD166, ALDH1A1,
      Lgr5, and several others. In this review we consider the evidence for these
      proteins as colon cancer stem cell markers and as prognostic indicators of colon
      cancer survival. Additionally, we discuss potential functions of these proteins
      and the implications this may have for development of therapies that target colon
      cancer stem cells.

PMID- 21196256
TI  - Can you hear me now? Understanding vertebrate middle ear development.
AB  - The middle ear is a composite organ formed from all three germ layers and the
      neural crest. It provides the link between the outside world and the inner ear,
      where sound is transduced and routed to the brain for processing. Extensive
      classical and modern studies have described the complex morphology and origin of
      the middle ear. Non-mammalian vertebrates have a single ossicle, the columella.
      Mammals have three functionally equivalent ossicles, designated the malleus,
      incus and stapes. In this review, I focus on the role of genes known to function
      in the middle ear. Genetic studies are beginning to unravel the induction and
      patterning of the multiple middle ear elements including the tympanum, skeletal
      elements, the air-filled cavity, and the insertion point into the inner ear oval
      window. Future studies that elucidate the integrated spatio-temporal signaling
      mechanisms required to pattern the middle ear organ system are needed. The longer
      term translational benefits of understanding normal and abnormal ear development
      will have a direct impact on human health outcomes.

PMID- 21196258
TI  - Kinase-driven pathways of EGFR in lung carcinomas: perspectives on targeting
      therapy.
AB  - Despite remarkable advances in oncology medicine, the prognosis of lung cancer
      patients has not greatly improved over the past few decades. To overcome the
      current limit, new classes of agents that specifically target particular cascades
      have been developed. Gefitinib and erlotinib, which are tyrosine kinase
      inhibitors specific for the epidermal growth factor receptor (EGFR), have
      provided hope for better survival. The relationship between the sensitivity to
      gefitinib and the tumors' EGFR mutations have allowed the selective and
      accelerated use of these therapies. However, their efficacy is still limited,
      predominantly due to side effects and drug resistance. Further development of
      rational clinical strategies will require greater clarification of the key
      signaling factors downstream of EGFR which are potential targets for cancer
      therapies. In this review, we describe the various observed abnormalities in
      EGFR, the mechanisms of activation of several critical signaling cascades in lung
      cancer. Summarizing the data gleaned from preclinical, and clinicopathological
      aspects, we discuss the molecular mechanisms that may underlie a possible
      successful response to the blockade of EGFR and/or its downstream signaling.

PMID- 21196260
TI  - Why YPEL3 represents a novel tumor suppressor.
AB  - Yippee-like 3 (YPEL3) was reported in 2004 as one of five family members of the
      Yippee protein with conservation in species down to slime molds. While reports of
      other YPEL family members have surfaced our laboratory was the first to report
      that YPEL3 is induced by the p53 tumor suppressor. Furthermore we demonstrated
      that YPEL3 is growth suppressive, triggering cellular senescence in human cell
      lines and is down-regulated in several human tumors. Studies with mouse YPEL3,
      originally named small unstable apoptotic protein (SUAP), confirmed that the gene
      encodes a growth suppressive highly unstable protein. In this review we show that
      transcriptionally active forms of p73 and p63, family members of p53, can
      transactivate the human YPEL3 gene. While there are several reported YPEL3
      transcripts and potentially 2 protein isoforms, no clear protein structure has
      been reported. As evidence mounts that YPEL3 is a tumor suppressor gene, studies
      aimed at understanding its biological function, regulation of gene expression and
      impact on tumorigenesis will help.

PMID- 21196259
TI  - Oxidative stress and endothelial dysfunction in cerebrovascular disease.
AB  - Maintenance of vascular tone by the endothelium involves the production of
      endothelium-derived nitric oxide (NO). NO, produced from endothelial nitric oxide
      synthase diffuses to the underlying smooth muscle to stimulate soluble guanylate
      cyclase, resulting in increased cyclic GMP levels, and subsequent smooth muscle
      relaxation and blood vessel dilatation. Endothelial dysfunction, manifested as
      diminished NO bioavailability, is a common feature of a number of vascular
      related diseases.. Oxidative stress can be defined as an imbalance between
      reactive oxygen species (ROS) production and/or impaired ROS metabolism that
      favours them being present in excess of physiological levels. Oxidative stress
      can negatively impact many cell types, including in the vasculature. There is now
      a wealth of evidence suggesting that oxidative stress is a major cause of
      endothelial dysfunction in the cerebral circulation. This review will summarize
      disease models in which both oxidative stress and endothelial dysfunction occur
      in the cerebral circulation, namely hypertension involving angiotensin II (Ang
      II), diabetes, subarachnoid hemorrhage, stroke and Alzheimer's disease. Molecular
      mechanisms by which oxidative stress occurs, (eg increased NADPH-oxidase
      activity) will also be discussed.

PMID- 21196257
TI  - Death pathways triggered by activated Ras in cancer cells.
AB  - Ras GTPases are best known for their ability to serve as molecular switches
      regulating cell growth, differentiation and survival. Gene mutations that result
      in expression of constitutively active forms of Ras have been linked to
      oncogenesis in animal models and humans. However, over the past two decades,
      evidence has gradually accumulated to support a paradoxical role for Ras proteins
      in the initiation of cell death pathways. In this review we survey the literature
      pointing to the ability of activated Ras to promote cell death under conditions
      where cancer cells encounter apoptotic stimuli or Ras is ectopically expressed.
      In some of these cases Ras acts through known effectors and well defined
      apoptotic death pathways. However, in other cases it appears that Ras operates by
      triggering novel non-apoptotic death mechanisms that are just beginning to be
      characterized. Understanding these mechanisms and the factors that go into
      changing the nature of Ras signaling from pro-survival to pro-death could set the
      stage for development of novel therapeutic approaches aimed at manipulating pro
      death Ras signaling pathways in cancer.

PMID- 21196262
TI  - The paradox of cancer cell apoptosis.
AB  - Resistance to apoptosis is an accepted property of human cancer cells and
      resistance to cancer therapy is often considered to involve increased resistance
      to apoptosis. However, comparison of the potential doubling times of human tumour
      cells with the volume doubling times of the tumour from which they are derived
      implies a high rate of apoptosis. For at least some cancer types, increased
      proliferation rate and correspondingly increased apoptosis is associated with a
      poor prognosis. How can resistance to apoptosis and apoptosis be reconciled? One
      possible resolution of this paradox is that at least two tumour cell populations
      are involved, a smaller, more rapidly growing population with self-renewal
      properties and resistance to apoptosis, and a larger, more slowly growing
      population that is susceptible to apoptosis. The progeny of smaller population
      thus maintains the larger population. This review describes the evidence for such
      a model and its implications for cancer therapy.

PMID- 21196261
TI  - Modulation of signaling between TM4SF5 and integrins in tumor microenvironment.
AB  - TM4SF5 is a transmembrane glycoprotein of the transmembrane 4 L six family, a
      branch of the tetraspanin family and highly expressed in many types of cancers.
      TM4SF5 induces epithelial-mesenchymal transition (EMT) by morphological changes
      resulting from inactivation of RhoA mediated by stabilized cytosolic p27kip1.
      TM4SF5-mediated EMT can lead to loss of contact inhibition and enhanced
      migration/invasion, presumably depending on cross-talks between TM4SF5 and
      integrins. An anti-TM4SF5 agent appears to target the second extracellular domain
      of TM4SF5, which is important for cross-talk with integrins, leading to a
      blockade of TM4SF5-mediated multilayer growth and migration/invasion. In
      addition, TM4SF5 engages in cross-talk with integrin alpha5 to induce and secrete
      VEGF, which in turn causes activation of angiogenesis in endothelial cells.
      Therefore, TM4SF5 plays a central regulatory role in a wide variety of
      physiological processes through cross-talk with integrins. This review presents
      current knowledge from in vitro and in vivo observations of the roles of TM4SF5
      integrin cooperation in hepatocellular carcinogenesis and discusses important
      areas for future investigation.

PMID- 21196263
TI  - Amino acid metabolism in intestinal bacteria: links between gut ecology and host
      health.
AB  - Bacteria in the gastrointestinal (GI) tract play an important role in the
      metabolism of dietary substances in the gut and extraintestinal tissues. Amino
      acids (AA) should be taken into consideration in the development of new
      strategies to enhance efficiency of nutrient utilization because they are not
      only major components in the diet and building blocks for protein but also
      regulate energy and protein homeostasis in organisms. The diversity of the AA
      fermenting bacteria and their metabolic redundancy make them easier to survive
      and interact with their neighboring species or eukaryotic host during transition
      along GI tract. The outcomes of the interactions have important impacts on gut
      health and whole-body homeostasis. The AA-derived molecules produced by
      intestinal bacteria affect host health by regulating either host immunity and
      cell function or microbial composition and metabolism. Emerging evidence shows
      that dietary factors, such as protein, non-digestible carbohydrates, probiotics,
      synbiotics and phytochemicals, modulate AA utilization by gut microorganisms.
      Interdisciplinary research involving nutritionists and microbiologists is
      expected to rapidly expand knowledge about crucial roles for AA in gut ecology
      and host health.

PMID- 21196264
TI  - KSRP, many functions for a single protein.
AB  - KSRP is a single-strand nucleic acids binding protein that affects RNA fate at
      multiple levels. KSRP modular structure and its complex pattern of post
      translational modifications underpin the interaction with a wide spectrum of RNA
      target sequences, as well as with other RNA-binding proteins and molecular
      adaptors. These interactions are important to the regulation of different steps
      of mRNA metabolism and, in turn, modulate several aspects of cellular
      proliferation and differentiation. In this review we will discuss in detail KSRP
      ability to i) promote decay of labile mRNAs interacting with some components of
      the mRNA decay machinery and ii) favor the maturation of a select group of
      microRNA precursors.

PMID- 21196265
TI  - Sphingolipid abnormalities in psychiatric disorders: a missing link in pathology?
AB  - Sphingolipids are biologically active lipids ubiquitously expressed in all
      vertebrate cells, especially those in the CNS. Aside from their essential roles
      as structural components of cell membranes, studies over the past two decades
      have shown that they play vital roles in cellular signaling, cell differentiation
      and proliferation, apoptosis and inflammation. Given these properties, it is not
      surprising that disruption of sphingolipid metabolism is strongly associated with
      several diseases that exhibit diverse neurological, psychiatric, and metabolic
      consequences. Here, we review the emerging roles of sphingolipids in disease
      pathogenesis in psychiatric disorders, including schizophrenia, bipolar disorder
      and major depression. Understanding sphingolipid metabolism and it dysregulation
      in human disease is significant for the development of new therapeutic
      approaches.

PMID- 21196266
TI  - EGFR tyrosine kinase inhibitors and multidrug resistance: perspectives.
AB  - Aim of present review is to provide an evidence-based update of mechanisms
      responsible for the onset of resistance to drug therapy by EGFR inhibitors,
      particularly with regards to TKIs. Among ABC transporters involved in MDR, P
      glycoprotein and BCRP have been considered the pumps responsible for TKIs
      treatment failure. Moreover, two subtypes of EGFR mutations have been described:
      mutations of the exons coding for tyrosine kinase domain (18 to 21) and
      truncating mutations (exons 2 to 7) that involve downstream effectors such as
      MAPK, PI3K/Akt, STAT. The first group of mutations can be considered as a
      hallmark of NSCLC and are responsible for the failure of TKIs while the second
      group of mutations leads to resistance. The strategies to overcome MDR and to
      bypass the kinase domain mutations have been addressed. Finally, for some first
      generation TKIs some perspectives as radiotracers for PET/SPECT diagnosis in
      tumor displaying P-gp and BCRP overexpression have been suggested.

PMID- 21196267
TI  - Breast cancer stem cells: a new challenge for breast cancer treatment.
AB  - The biggest challenge for cancer research is relapses that occur in patients
      undergoing chemotherapy and radiotherapy, suggesting that some cells in tumors
      escape targeted treatment. Key questions are why relapses occur and why current
      therapies fail to remove all cancer cells. The cancer stem-cell hypothesisis
      based on the fact that not all cells within a tumor are similar. Other than
      tumorigenesis and metastasis, cancer stem cells have some properties that are
      similar to those of normal stem cells, such as self-renewal and differentiation.
      Accordingly, breast cancer stem cells may arise from mutation of normal mammary
      stem cells or progenitor cells. Cancer stem cell regulation involves several
      factors, such as Wnt, Notch, and Hedgehog, mutations of which endow cancer stem
      cells with the capacity for self-renewal. Moreover, epithelial mesenchymal
      transition and microRNAs recently have been shown to regulate the "stemness " of
      cancer cells. Targeting cancer stem cells could prevent relapse and provide new
      hope for cancer prevention.

PMID- 21196268
TI  - Effects of omega-3 polyunsaturated fatty acids on cardiac myocyte protection.
AB  - Many epidemiologic, observational and randomized human clinical trials have
      demonstrated beyond doubt the protective cardiovascular effects of omega-3
      polyunsaturated fatty acids (PUFAs). Cardiac myocytes protection by omega-3 PUFAs
      involves several mechanisms which might have a synergistic effect. This review
      provides a summary of the in vitro and in vivo effects of omega-3 PUFAs on
      cardiac myocytes health and reports the outcome of a number of clinical trials in
      patients consuming omega-3 PUFAs.

PMID- 21196270
TI  - The roles of ADAMTS metalloproteinases in tumorigenesis and metastasis.
AB  - The human ADAMTS (a disintegrin and metalloproteinase with thrombospondin-like
      motifs) family of 19 secreted, multidomain proteolytic enzymes is involved in a
      wide range of biological processes including ECM assembly and degradation,
      hemostasis, organogenesis and the regulation of angiogenesis. Defects in certain
      family members give rise to inherited human genetic diseases, while aberrant
      expression of other ADAMTSs has been linked to the pathogenesis of arthritis and
      cancer. Several ADAMTSs act as tumor or metastasis suppressors whose functions
      are lost either by mutation or epigenetic silencing during tumor progression.
      This review looks in depth at the involvement of ADAMTSs as positive and negative
      mediators in cancer growth and spread.

PMID- 21196271
TI  - Nitric oxide signalling in the regulation of cardiovascular and platelet
      function.
AB  - Nitric oxide (NO) exerts important protective actions on the cardiovascular
      system. Generated from L-arginine by the action of endothelial (or type 3) nitric
      oxide synthase (NOS3), NO regulates vascular tone in humans and causes
      endothelium-dependent vasodilation. Additionally endothelium-derived NO exerts
      antioxidant, antiproliferative and anti-inflammatory properties, thus playing an
      important role in inhibiting the atherosclerotic process. With regard to effects
      on platelet function, NO produced by both endothelial cells and platelets has
      important antithrombotic effects by decreasing platelet activation, a phenomenon
      which contributes importantly to the thrombotic tendency which accompanies a
      variety of cardiovascular disease states. Additionally, by inhibiting platelet
      activation, NO prevents heterotypic aggregation between platelets and monocytes,
      thereby reducing monocyte-platelet aggregates in the circulation which are
      believed to play an important pathophysiological role in the initiation and
      progression of atherosclerosis. New therapeutic interventions aimed at improving
      NO availability have been investigated in animal as well as in vitro studies and
      show considerable promise, but it remains to be seen whether such therapies will
      be equally efficacious in humans clinically.

PMID- 21196272
TI  - Recent advances in meiotic maturation and ovulation: comparing mammals and
      pisces.
AB  - Meiotic maturation is a complex process that involves resumption of meiosis in
      response to preovulatory luteinizing hormone (LH) surge just before ovulation.
      High levels of cAMP in oocytes maintain meiotic arrest at diplotene of prophase I
      in mammals and pisces. In mammals, the process by which LH induces recommencement
      of meiosis involves breakdown of oocyte-somatic cells communication, which is
      followed by a drop in intracellular cAMP levels that in turn causes exit from
      meiotic arrest. Maturation promoting factor (MPF) then accomplishes progression
      of oocytes to reach first metaphase followed by second metaphase after
      reinitiating meiosis. Pisces require precise completion of oocyte growth
      involving vitellogenesis before the entry of meiotic maturation. Then, both
      mammalian and fish oocytes enters resumption of meiosis involving germinal
      vesicle breakdown, chromosome condensation, assembly of meiotic spindle, and
      formation of first polar body. However, this process in pisces is regulated by
      three major mediators, LH, 17alpha,20beta-dihydroxy progesterone and MPF which
      are unique. The molecular mechanisms of meiotic maturation and ovulation by
      comparing mammalian and piscine research have been dealt in this review.

PMID- 21196269
TI  - Emerging metabolic targets in cancer therapy.
AB  - Cancer cells are different from normal cells in their metabolic properties.
      Normal cells mostly rely on mitochondrial oxidative phosphorylation to produce
      energy. In contrast, cancer cells depend mostly on glycolysis, the aerobic
      breakdown of glucose into ATP. This altered energy dependency is known as the
      "Warburg effect" and is a hallmark of cancer cells. In recent years,
      investigating the metabolic changes within cancer cells has been a rapidly
      growing area. Emerging evidence shows that oncogenes that drive the cancer
      promoting signals also drive the altered metabolism. Although the exact
      mechanisms underlying the Warburg effect are unclear, the existing evidence
      suggests that increased glycolysis plays an important role in support malignant
      behavior of cancer cells. A thorough understanding of the unique metabolism of
      cancer cells will help to design of more effective drugs targeting metabolic
      pathways, which will greatly impact the capacity to effectively treat cancer
      patients. Here we provide an overview of the current understanding of the Warburg
      effect upon tumor cell growth and survival, and discussion on the potential
      metabolic targets for cancer therapy.

PMID- 21196274
TI  - Metastatic potential of tumor-initiating cells in solid tumors.
AB  - The lethality of cancer is mainly caused by its properties of metastasis, drug
      resistance, and subsequent recurrence. Understanding the mechanisms governing
      these properties and developing novel strategies to overcome them will greatly
      improve the survival of cancer patients. Recent findings suggest that tumors are
      comprised of heterogeneous cell populations, and only a small fraction of these
      are tumorigenic with the ability to self-renew and produce phenotypically diverse
      tumor cell populations. Cells in this fraction are called tumor-initiating cells
      (TICs) or cancer stem cells (CSCs). TICs have been identified from many types of
      cancer. They share several similarities with normal adult stem cells including
      sphere-forming ability, self-renewability, and expression of stem cell surface
      markers and transcription factors. TICs have also been proposed to be responsible
      for cancer metastasis, however, scarce evidence for their metastatic potential
      has been provided. In this review article, we have attempted to summarize the
      studies which have examined the metastatic potential of TICs in solid tumors.

PMID- 21196273
TI  - RhoA can lead the way in tumor cell invasion and metastasis.
AB  - The Rho family of GTPases is well-established regulators of cell migration, and
      has been implicated in the process of tumor cell invasion and metastasis. The
      RhoA signaling pathway is strongly correlated with the ability of tumor cells to
      invade and successfully establish metastases. In this review, we begin by
      discussing the gene expression data correlating Rho expression with metastasis,
      and then discuss two emerging concepts that help explain the underlying
      mechanisms by which RhoA may promote tumor metastasis. First, the use of
      sophisticated biosensor probes has revealed that RhoA is active in membrane
      protrusions. Second, the RhoA pathway affects the invasive behavior of tumor
      cells by promoting invadopodia, amoeboid migration, and the plasticity of tumor
      cells to modulate their migratory properties. Thus, our view of the role of the
      RhoA pathway in metastasis is evolving to include a previously unappreciated
      function at the leading edge.

PMID- 21196275
TI  - CCN proteins in normal and injured liver.
AB  - CCN proteins are small secreted cysteine-rich proteins containing up to four
      individual structural modules including an insulin-like growth factor binding
      domain, a von Willebrand Factor type C motif, a thrombospondin type I module and
      a carboxyl-terminal cystine knot. Actually, there is a large body of evidence
      suggesting that members of the CCN protein family encompass an expansive
      repertoire of functions in crucial areas including control of development, cell
      fate, angiogenesis, tumorigenesis, osteogenesis, cell adhesion, mitogenesis,
      migration, chemotaxis, and cell survival. Moreover, this family is supposed to
      modulate signalling of integrins, transforming growth factor-betas, bone
      morphogenetic proteins, vascular endothelial growth factor, Notch and factors
      that mediate signals via the canonical Wingless-type MMTV integration site
      family. However, several of these properties are not substantiated by
      experimental data but were deduced from proteins sharing one or more of the
      structural modules with these proteins. In this review, the actual knowledge of
      biological activities and molecular involvement of CCN proteins in maintenance of
      liver health and in initiation and progression of hepatic diseases is summarized
      and discussed.

PMID- 21196276
TI  - EGFR tyrosine kinases inhibitors in cancer treatment: in vitro and in vivo
      evidence.
AB  - The increasing understanding of the molecular mechanisms of neoplastic
      transformation and progression has prompted the search for novel drugs that could
      interfere with the intracellular targets involved in this process. EGFR is
      implicated in the development and progression of the majority of the common human
      epithelial cancer; therefore different agents have been developed to block EGFR
      activation in cancer cells. This review focuses on EGFR-tyrosine kinase
      inhibitors in clinical practice that interfere with ATP binding, inhibiting
      tyrosine kinase activity and subsequently blocking signal transduction from EGFR.
      We report current knowledge on molecular mechanisms underlying the anticancer
      activity of EGFR-tyrosine kinase inhibitors in preclinical models, with
      particular attention to EGFR downstream effectors responsible for treatment
      efficacy or resistance.

PMID- 21196278
TI  - Oxidative stress and endothelial dysfunction during sepsis.
AB  - Endothelial activation and dysfunction play a key role in the pathogenesis of
      sepsis. During septic shock, endothelial dysfunction is involved in
      microcirculation impairment and organ dysfunction. Reactive oxygen species (ROS)
      and reactive nitrogen species (RNS) have several potentially important effects on
      endothelial function and are implicated in physiological regulation and disease
      pathophysiology. The imbalance between the production of ROS and their effective
      removal by non-enzymatic and enzymatic antioxidants systems could induce
      endothelial dysfunction with alterations of vascular tone, increases in cell
      adhesion properties (leukocytes and platelet adhesion), increase in vascular wall
      permeability and a pro-coagulant state. Increasing evidence supports the idea
      that the principal cause of EC dysfunction during sepsis is cell injury. ROS and
      RNS contribute to mitochondrial dysfunction by a range of mechanisms and induce
      both necrotic and apoptotic cell death. Understanding the mechanisms underlying
      the generation of ROS and RNS in endothelial cells and the causes of endothelial
      dysfunction in sepsis may help provide therapeutic strategies to tackle
      endothelial dysfunction and microcirculatory failure in sepsis.

PMID- 21196277
TI  - Anti-EGFR monoclonal antibody in cancer treatment: in vitro and in vivo evidence
AB  - The complexity of EGFR signaling network suggests that the receptor could be
      promising targets for new personalised therapy. In clinical practice two
      strategies targeting the receptor are available; they utilise monoclonal
      antibodies, directed towards the extracellular domain of EGFR, and small molecule
      tyrosine kinase inhibitors, which bind the catalytic kinase domain of the
      receptor. In this review, we summarise currently known pre-clinical data on the
      antitumor effects of monoclonal antibodies, which bind to EGFR in its inactive
      configuration, competing for ligand binding and thereby blocking ligand-induced
      EGFR tyrosine kinase activation. As a consequence of treatment, key EGFR
      dependent intracellular signals in cancer cells are affected. Data explaining the
      mechanisms of action of anti-EGFR monoclonal antibodies, currently used in
      clinical setting and under development for the treatment of solid tumors, are
      revised with the aim to provide an overview of the most important preclinical
      studies showing the impact of this class of EGFR targeted agents on tumor
      biology.

PMID- 21196279
TI  - Biomarker discovery and identification from non-small cell lung cancer sera.
AB  - Currently, serum biomarkers might usually be thought not to be used for early
      detection of lung cancer by some researchers. In this study, we used a highly
      optimized ClinProt-matrix-assisted laser desorption/ionization time-of flight
      mass spectrometer (MALDI-TOF-MS) to screen non-small cell lung carcinoma (NSCLC)
      markers in serum. A training set of spectra derived from 45 NSCLC patients, 24
      patients with benign lung diseases (BLDs) and 21 healthy individuals, was used to
      develop a proteomic pattern that discriminated cancer from non-cancer
      effectively. A test set, including 74 cases (29 NSCLC patients and 45 controls),
      was used to validate this pattern. After cross-validation, the classifier showed
      sensitivity and specificity, 86.20% and 80.00%, respectively. Remarkably, 100% of
      early stage serum samples could be correctly classified as lung cancer.
      Furthermore, the differential peptides of 1865Da and 4209Da were identified as
      element of component 3 and eukaryotic peptide chain release factor GTP-binding
      subunit ERF, respectively. The patterns we described and peptides we identified
      may have clinical utility as surrogate markers for detection and classification
      of NSCLC.

PMID- 21196280
TI  - Postprandial transcriptome associated with virgin olive oil intake in rat liver.
AB  - Liver has been proposed as a gatekeeper that regulates postprandial lipemia and a
      potential target for regulation by acute intake of virgin olive oil. To
      characterize the hepatic gene expression response to a fat gavage, male rats were
      fed a bolus of 5 ml of extra-virgin olive oil and the hepatic mRNA expression
      analyzed 4 hours later using DNA microarrays. To provide an initial screening of
      candidate genes, only twenty one with remarkably modified expression between both
      conditions (signal log2 ratio > 2.5 or < -2.5) were considered and confirmed by
      quantitative real time PCR. Those that presented biological significance were
      also analyzed 8 hours after the experimental approach. Hepatic A2m Slc13a5 and
      Nrep mRNA expressions were found significantly changed in both studied conditions
      and showed the highest significant associations with postprandial plasma
      triglycerides and lack of association with basal triglyceridemia. These results
      highlight new gene regulation in liver by postprandial triglyceridemia and will
      help to understand the complex human pathology providing the involvement of
      hepatic proteins and new strategies to cope with postprandial metabolism.

PMID- 21196281
TI  - EGFR activation monitored by SW-FCCS in live cells.
AB  - Single wavelength fluorescence cross-correlation spectroscopy (SW-FCCS) has been
      applied to the quantitative determination of molecular interactions at
      equilibrium for different molecular systems in vitro and in vivo, including
      living cells and organisms. Here we report for the first time the measurement of
      an activation and time dependent interaction between a cytosolic and a membrane
      bound protein by SW-FCCS in live cells. On the example of the epidermal growth
      factor (EGF) receptor (EGFR) we confirm the existence of pre-formed dimers in the
      absence of stimulation and demonstrate that the activation of the receptor can be
      detected by the phosphorylation dependent binding of a phosphotyrosine binding
      (PTB) domain. SW-FCCS results indicate that in CHO cells there is low specific
      interaction between PTB and EGFR, possibly indicating a low level of EGFR
      phosphorylation even in the absence of EGF stimulation. After EGF stimulation the
      interaction between PTB and EGFR increases significantly in a time dependent
      manner.

PMID- 21196282
TI  - Single nucleotide polymorphisms in IL-4Ra, IL-13 and STAT6 genes occurs in brain
      glioma.
AB  - Gliomas are aggressive brain tumor. Association studies were consistent for an
      inverse association between asthma and allergic conditions (IgE levels) and risk
      of glioma. Studies reported that the IL-4Ra, IL-13 and STAT6 genes played a
      relatively strong role in IgE production or allergy. This population-based case
      control study aimed to find potential association between single nucleotide
      polymorphisms IL-13rs20541, IL-4Rars1801275 and glioma susceptibility in
      population, as well as STAT6 rs1059513 and STAT6 rs324015. Among non-smokers,
      homozygote GG of STAT6 4610A/G showed an increased association with risk of
      glioma compared with AA (adjusted OR=1.691, 95%CI=1.152-2.481, p=0.007, corrected
      p=0.028), and the haplotype with A allele at rs1059513 and G allele at rs324015
      was revealed to increase glioma risk significantly (OR=1.321,95%CI= 1.081-1.614,
      p=0.007,corrected p=0.028). GG genotype of STAT6 4610A/G was a significant risk
      factor compared with AA in glioblastoma (adjusted OR=1.856, 95%CI=1.153-2.987,
      p=0.011, corrected p=0.044). GG of STAT6 4610A/G was significantly related to
      increased WHO IV risk compared with AA (adjusted OR=1.591,95%CI=1.030-2.459,
      p=0.036, corrected p=0.144). Interaction between IL-13 Arg130Gln and IL-4Ra
      Gln576Arg was observed in decreasing glioma risk (p=0.045).

PMID- 21196284
TI  - Allergy in the tropics: the impact of cross-reactivity between mites and ascaris.
AB  - Allergic diseases and nematode infections such as ascariasis are important health
      problems in underdeveloped tropical countries. The co-exposure to Ascaris
      lumbricoides and the domestic mites Blomia tropicalis and Dermatophagoides
      pteronyssinus induces a strong Th2 and immunomodulatory responses that can modify
      the natural history of both diseases. An associate phenomenon of these particular
      environmental conditions is cross reactivity between mite and Ascaris allergens.
      We demonstrated a high IgE cross reactivity between the allergenic extracts from
      both sources and that several already known allergens like tropomyosin and
      glutathione-s-tranferases are involved. Although this cross reactive antibody
      response has not been completely analyzed, there are clinical and experimental
      evidences suggesting that it could be an important component of the complex
      interactions between ascariasis and mite allergy. For example, it may affect the
      specificity of serological IgE tests for diagnosing both ascariasis and allergic
      diseases and, in consequence, the results of epidemiological surveys evaluating
      the predisposing or protecting role of ascariasis on allergy. In this review we
      discuss the potential role of cross reactivity on several aspects of allergy in
      the tropics that have been the matter of a number of investigations, some of them
      with controversial results.

PMID- 21196283
TI  - Bioinformatics approach for the validation of non-small cell lung cancer
      biomarkers.
AB  - Non-small cell lung cancer (NSCLC) accounts for nearly 1 million deaths annually,
      worldwide. Conventional treatments offer limited benefits and patients have a
      survival rate of approximately 1 year. A biomarker for NSCLC could provide the
      potential benefits of early diagnosis, prognosis and could lead to important
      applications such as drug targeting. In a search for a biomarker with prognostic
      value, we reviewed the literature and tested potential biomarkers by performing a
      meta-data analysis using public databank of NSCLC biopsies containing gene
      expression data and clinical and pathologic information from 111 patients. We
      generated standard Kaplan-Meier mortality curves by clustering patients according
      to either biomarker expression levels or NSCLC stage grouping. Our statistical
      analyses show that all 60 potential biomarkers analyzed here have no prognostic
      value for NSCLC patient outcome.

PMID- 21196285
TI  - Influence of tissue particles on Fas expression in idiopathic interstitial
      pneumonia.
AB  - Idiopathic interstitial pneumonia (IIP) is a progressive fibrosing interstitial
      pneumonia of unknown etiology with a poor prognosis. The aim of this study is to
      prove the occurrence of particle deposition and particle-induced tissue damage in
      IIP by examining proapoptotic Fas expression with in-air microparticle induced X
      ray emission (in-air micro-PIXE) analysis. A total of 21 patients were enrolled.
      Lung tissues from 12 IIP patients and nontumorous lung tissues from 9 lung cancer
      patients (as a control) were subjected to in-air micro-PIXE analysis. The
      distribution of particles in lung tissue was compared with the localization of
      Fas expression by immunohistochemistry. Silicon (Si) was identified in 58.3% of
      IIP samples and 44.4% of control samples. Iron (Fe) was identified 25% in IIP
      samples and 11.1% in control samples. The mean lung tissue content of Si and Fe
      relative to S did not differ between IIP and control patients. Only two IIP
      patients showed the co-localization of Si and Fe deposition with Fas expression.
      Adaptation of this method would contribute to assess the influence of particles
      on IIP.

PMID- 21196286
TI  - Detection of airborne trichothecene-producing Fusarium species in chicken houses.
AB  - One hundred and forty three airborne Fusarium isolates in chicken houses
      belonging to seven Fusarium species were analyzed by PCR with Tri5 gene as a
      specific marker of mycotoxin product . The result of Tri5 gene sequence analysis
      indicates that the PCR amplification products were 89%-96% identical to the
      previously reported Tri5 genes, which were all amplified from four F. poae
      isolates. T-2 toxin and DON was measured by immunoaffinity column and high
      performance liquid chromatography in Tri5-positive F. poae isolates after being
      cultured at constant and alternating temperatures. The production of T-2 toxin
      under alternating temperatures was 14 and 53 times higher than those at constant
      temperature of 8  degrees C and 25  degrees C. No DON was detected under either
      testing temperature condition. It is concluded that T-2 toxin-producing F. poae
      isolates were present in poultry houses, and the concentration of T-2 toxin
      produced by Tri5-positive F. poae isolates was increased under alternating
      temperatures. The application of Tri5-PCR associated with IMC-HPLC is an
      effective and accurate method for rapid detection of T-2 and DON mycotoxins.

PMID- 21196288
TI  - Impact of inflammation on male fertility.
AB  - The male uro-genital tract is susceptible to gram-negative bacterial infections
      that produce a state of inflammation, particularly in the testis and epididymis.
      Development of germline stem cells into motile spermatozoa takes place in these
      organs and thus any impairment therein has a direct effect on male fertility. A
      number of factors are known to impair male fertility including environmental and
      chemical factors, lifestyle, and infections. The last is a little-known and
      poorly understood cause of male sub-/infertility. The presence of the pro
      inflammatory cytokines like tumor necrosis factor-alpha (TNF- alpha), interleukin
      1alpha (IL-1alpha) and interleukin-1beta (IL-1beta) in the male uro-genital tract
      following bacterial infections suggests that such infections could have cytokine
      mediated anti-fertility effects. Furthermore, inflammation has been associated
      with elevated levels of reactive oxygen species and oxidative stress both of
      which affect male fertility. The present article summarizes the effects of
      inflammation on the testis, epididymis and spermatozoa. We review the
      correlations between inflammation and oxidative stress vis-a-vis spermatogenesis
      and discuss the implications of infections on male fertility/infertility and
      assisted reproductive technologies for the male.

PMID- 21196287
TI  - Inhibiting the Na+/H+ exchanger reduces reperfusion injury: a small animal MRI
      study.
AB  - We used magnetic resonance imaging (MRI) to assess the efficacy of Na+/H+
      exchanger isoform 1 (NHE-1) inhibition following cerebral ischemia. Transient
      focal cerebral ischemia was induced in wild-type controls (NHE-1(+/+)), NHE-1
      genetic knockdown mice (NHE-1(+/-)), and NHE-1(+/+) mice treated with the
      selective NHE-1 inhibitor HOE642. Diffusion weighted imaging (DWI) revealed a
      brain lesion as early as 1 hour following reperfusion and illustrated significant
      protection in NHE-1(+/-) mice (16.2 +/- 7.9 mm3 in NHE-1(+/-) mice vs. 47.5 +/-
      16.6 mm3 in NHE-1(+/+) mice). Knockdown of NHE-1 showed significantly smaller
      infarct at 72 hours on T2 imaging (21.2 +/- 12.6 mm3 in NHE-1(+/-) mice vs. 64.6
      +/- 2.5 mm3 in NHE-1(+/+) mice). Administration of HOE642 prior to reperfusion or
      during early reperfusion reduced ischemic damage. Thus, high resolution T2 images
      can be used for consistent and precise calculation of lesion volumes, while
      changes of DWI are a sensitive early marker of ischemic injury. The results of
      this study demonstrate the therapeutic potential for inhibition of NHE-1 in
      treating cerebral ischemia.

PMID- 21196289
TI  - Lights and shadows concerning platelet products for musculoskeletal regeneration.
AB  - Various types of platelet (PLT) products, such as Platelet Rich Plasma (PRP) and
      Platelet Gel (PG), derived from autologous peripheral blood, have been used for
      tissue repair. The good clinical outcomes, due mainly to their safety and Growth
      Factor (GF) content, have led to a wide use of PLT products in many fields of
      medicine. However, until now the existing literature adds controversies to the
      use of PLT concentrates. When talking about PLTs and their products, a great
      number of variables have to be considered. These variables are mainly related to
      PRP preparation methods, the type of activators, intra- and inter-species
      variability, types of pathology to be treated, the ways and times of
      administration and the association of PRP or PG with other treatments. This
      review considers and discusses these causes of variability with particular
      attention to orthopaedic implications. The possibility of improving the knowledge
      on variables affecting therapeutic efficacy will surely help in addressing the
      best combination of factors implied in the different steps of PLT concentrate
      preparation and use.

PMID- 21196290
TI  - Spore trap analysis and MSQPCR in evaluating mold burden: a flooded gymnasium
      case study.
AB  - A school gymnasium was accidentally flooded by the fire-suppression sprinkler
      system. The surface water was removed immediately and, after 10 days, a
      professional firm engaged to dry the environment. Twenty five days after the
      flooding, the school decided to evaluate whether there was any mold growth in the
      gymnasium. The inspector used two approaches, traditional air samples or a DNA
      based analysis of dust samples. Thirty five-minute air samples (for total of 75 L
      of air each sample) were collected with Air-O-CellTM (AOC) cassettes and the mold
      structures (MS) were quantified by microscopy. These samples were compared to two
      identical outdoor air samples. As an alternative, two dust samples were collected
      and quantified by mold specific quantitative PCR (MSQPCR). Comparisons of indoor
      to outdoor mold concentrations in air samples were inconclusive, but applying
      MSQPCR to the investigation of this water-damaged environment provided a more
      reliable and useful answer to the extent of mold contamination than did the spore
      trap analysis.

PMID- 21196291
TI  - Overexpression of p204 leads to abnormal embryos and osteogenesis in zebrafish.
AB  - p204, an inteferon-inducible protein, is known to play an important role in
      modulating cell proliferation, cell cycling, and the differentiation of various
      tissues, including osteoblasts. In order to determine the role of p204 during
      development in vivo, the teleost zebrafish (Danio rerio), an established
      vertebrate model for developmental studies, was employed. p204 cDNA was
      introduced into zebrafish by microinjection, and p204 was ectopically expressed
      throughout the whole embryo during the early stages of zebrafish embryogenesis,
      then its expression gradually decreased, mainly in ventrally located cells and
      retina capsules. Importantly, overexpression of p204 in zebrafish resulted in
      striking malformations such as bent spine and expanded belly. Furthermore, the
      expressions of some genes (vent, runx2b, osn) involved in dorsoventral patterning
      and osteogenesis were significantly upregulated after p204 injection. This study
      provides not only the in vivo evidences demonstrating the role of p204 during
      embryonic development, but also new insights into the molecular mechanism by
      which p204 mediate osteogenesis.

PMID- 21196292
TI  - BRCA1-related gene signature in breast cancer: the role of ER status and
      molecular type.
AB  - There is an ongoing debate whether hereditary breast cancer is a clinical entity
      distinct from sporadic breast cancer. We tried to shed some light on this issue
      by comparing the molecular profiles of these two types of cancer using DNA
      microarrays. Our results show that a previously reported marked difference
      between BRCA1-mutation linked and sporadic breast cancer was probably due to
      uneven stratification of samples with different ER status and basal-like versus
      luminal-like subtype. We observed that apparent difference between BRCA1-linked
      and other types of breast cancer found in univariate analysis was diminished when
      data were corrected for ER status and molecular subtype in multivariate analyses.
      In fact, the difference in gene expression pattern of BRCA1-mutated and sporadic
      cancer is very discrete. These conclusions were supported by the results of Q-PCR
      validation. We also found that BRCA1 promoter hypermethylation had similar effect
      on global gene expression as mutation-induced protein truncation. Thus, in the
      molecular studies of hereditary breast cancer, BRCA1 promoter methylation should
      be recognized and considered together with gene mutation.

PMID- 21196293
TI  - Aberrant methylation as a main mechanism of TSGs silencing in PTC.
AB  - In the present study the role of tumour suppressor genes (TSGs) hypermethylation
      and genetic instability of LOH/MSI type in thyroid tumorigenesis was assessed.
      Expression, methylation status and presence of LOH/MSI were analyzed for 8 TSGs
      selected from imprinted (IR) and non-imprinted (NIR) chromosomal regions in
      papillary thyroid carcinomas (PTCs) and nodular goitres (NGs). The results show
      that methylation-induced gene silencing occurs at an early step of thyroid
      carcinogenesis and involves multiple genes. Genetic changes of LOH/MSI type are
      less frequent. In PTC samples, the lack of significant differences in the
      frequency of LOH in IR and NIR suggests that it is not a key mechanism changing
      the pattern of gene expression. Co-methylation observed both in NG and PTC raises
      a possibility that, in thyroid tissue, methylation-induced silencing may occur
      not only in malignant transformation but also in functional context. We did not
      recognize any of the studied TSGs - in regard to aberrant methylation status or
      LOH/MSI frequency - as a selective molecular marker in thyroid tumorigenesis.

PMID- 21196294
TI  - Repression of Slc24a5 can reduce pigmentation in chicken.
AB  - Slc24a5 is a putative cation transporter, which is a member of the potassium
      dependent sodium-calcium ion exchanger family. Association of the Slc24a5 gene
      with pigmentation has been established in Zebrafish, mice and humans. Despite
      these findings, its function in chicken remains unknown. The intent of this study
      was to describe the association of Slc24a5 with respect to melanin deposition in
      the chicken using RNAi. The objective was to detect the variety of melanin
      deposition caused by the down-regulation of Slc24a5 in chicken retinal pigment
      epithelium (RPE) cells. Nine siRNAs that targeted against Slc24a5 mRNA were found
      to be effective in suppressing Slc24a5 gene expression in 293FT cells. The most
      effective target tested effectively inhibited Slc24a5 expression in mRNA and
      subsequently reduced protein levels in RPE cells. These results show that down
      regulation of Slc24a5 results in a reduction of melanin content, as well as a
      decrease of melaeneous type beta and type chi melanosomes simultaneously. Taken
      together, this work suggests that Slc24a5 function is conserved in the chicken,
      and necessary for melanin synthesis.

PMID- 21196295
TI  - KHYG-1 and NK-92 represent different subtypes of LFA-1-mediated NK cell
      adhesiveness.
AB  - Novel cancer cellular therapy approaches involving long-term ex vivo IL-2
      stimulated highly cytotoxic natural killer (NK) cells are emerging. However,
      adhesion properties of such NK cells are not very well understood. Herein, we
      describe the novel observation of permanently activated alphaLbeta2 integrin
      leukocyte function-associated antigen (LFA)-1 adhesion receptor in long-term IL-2
      activated NK cells and the permanent NK cell lines KHYG-1 and NK-92. We show that
      such cytokine activated NK effectors constitutively adhered to the LFA-1-ligand
      ICAM-1, whereas binding to the lower affinity ligand ICAM-3 required additional
      exogenous activating conditions. The results demonstrate an extended conformation
      and an intermediate affinity state for the LFA-1 population expressed by the NK
      cells. Interestingly, adhesion to ICAM-1 or K562 induced pronounced cell
      spreading in KHYG-1, but not in NK-92, and partially in long-term IL-2 stimulated
      primary NK cells. It is conceivable that such differential adhesion
      characteristics may impact motility potential of such NK effectors with relevance
      to clinical tumor targeting. KHYG-1 could be a useful model in planning future
      targeted therapeutic approaches involving NK effectors with augmented functions.

PMID- 21196296
TI  - Loss of mitochondria in ganglioneuromas.
AB  - A shift in cellular energy production from oxidative phosphorylation (OXPHOS) to
      glycolysis, even under aerobic conditions, is called the Warburg effect. To
      elucidate changes of the mitochondrial energy metabolism in ganglioneuroma (GN)
      individual OXPHOS enzymes were analyzed by activity assays and by
      immunohistochemical staining methods. GN (n=7) showed a significant reduction in
      the activity and content of OXPHOS enzymes. Citrate synthase activity was also
      severely diminished in GN compared to normal cortical kidney (p=0.0002) and
      adrenal (p=0.0024) tissues. Furthermore, the mitochondrial membrane protein porin
      was undetectable or significantly reduced. Accordingly, a reduction of the copy
      number of mitochondrial DNA was observed in GN compared to cortical kidney
      tissue. The striking decline of mitochondrial mass is specific for GN but not for
      neuroblastoma, in which a reduction of the OXPHOS complexes without reduction of
      mitochondrial mass was reported. Knowledge of the mechanism by which tumor cells
      achieve the Warburg effect will provide a starting point for functional studies
      aimed at restoring aerobic energy metabolism as a potential new therapeutic
      strategy to treat malignancies.

PMID- 21196297
TI  - Heterogeneity of mitochondrial energy metabolism in classical triphasic Wilms'
      tumor.
AB  - Metabolic changes are observed in a variety of tumors. The nature of the changes
      in aerobic energy metabolism differs between tumor types. Therefore,
      immunohistochemical staining, enzymatic measurements and immunoblot analysis were
      used to determine alterations of oxidative phosphorylation (OXPHOS) in classic
      triphasic Wilms' Tumor (WT). Our studies revealed that the epithelial, stromal
      and blastemal elements of this tumor differ in their energy metabolism. Compared
      to unaffected kidney tissue, normal mitochondrial mass was observed in the
      epithelial and blastemal regions of WT, whereas the stroma showed a massive down
      regulation of mitochondria, as indicated by low porin content, low citrate
      synthase activity, and reduced mtDNA copy number. All OXPHOS enzyme activities
      were reduced in all WT samples, with the exception of two epithelial-dominant
      cases, which showed up-regulation of complex III activity compared to control
      kidney tissues. Interestingly, our studies show that, even within a specific
      tumor entity, cell-type-specific alterations of aerobic energy metabolism can
      occur, although all cell types showed a clear tendency toward a reduced aerobic
      energy metabolism.

PMID- 21196298
TI  - Alterations of respiratory chain complexes in sporadic pheochromocytoma.
AB  - Succinate dehydrogenase (SDH) has been associated with carcinogenesis in
      hereditary pheochromocytoma (PC) and paraganglioma. We investigated if a similar
      association applies to sporadic pheochromocytoma. No genetic alteration was found
      in the SDHB, SDHC or SDHD genes of sporadic PC. However, in eight of nine
      sporadic PCs the SDH activity was, on average, reduced by 40%; moreover, the
      activities of the other oxidative phosphorylation (OXPHOS) complexes and citrate
      synthase were significantly lower compared to normal kidney tissue. Furthermore,
      immunohistochemical staining revealed a significant down-regulation of
      respiratory chain complexes. Since no pathogenic mutations were detected in the
      von Hippel-Lindau (VHL) gene, we can rule out that VHL deficiency is causing the
      general reduction of OXPHOS enzymes observed in the PCs investigated. In contrast
      to the single enzyme defects found in a subset hereditary PCs, a more generalized
      reduction of mitochondrial respiration seems to be present in most sporadic PCs.
      Strikingly, one of the nine PCs showed specific loss of complex I and a
      compensatory up-regulation of complexes II-V, which is a phenotype usually
      characteristic of oncocytic tumors.

PMID- 21196300
TI  - Identifying serum biomarkers for TACE therapy efficiency of hepatocellular
      carcinoma.
AB  - Transcatheter Arterial Chemoembolization (TACE) is the first line of treatment in
      inoperable hepatocellular carcinoma. Magnetic affinity beads can be used to
      extract peptides from un-fractionated serum samples. Matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) can detect
      the presence and the molecular mass of peptides. In this study, we used a highly
      optimized ClinProt-matrix-assisted laser desorption/ionization time-of flight
      mass spectrometer (MALDI-TOF-MS) to screen hepatocellular carcinoma markers for
      TACE. 40 sera from 20 patients, including before and after TACE to explore those
      biomarkers, might be related with therapy efficiency, and some of the patients
      who received another therapy were analyzed as well. The spectra were analyzed
      statistically using FlexAnalysisTM and Clin-ProtTM bioinformatic software. The
      seven most significant differential peaks (p < 0.0.5) were selected out by
      ClinProTool software to identify hepatocellular carcinoma markers for TACE
      therapy. Furthermore, the differential peptide of 3883Da was identified as plasma
      serine protease inhibitor precursor (Protein C inhibitor). This study provides a
      direct link between peptide marker profiles and TACE therapy, and the markers may
      have clinical utility for monitoring efficiency of therapy.

PMID- 21196299
TI  - EPO attenuates inflammatory cytokines by Muller cells in diabetic retinopathy.
AB  - Diabetic retinopathy (DR) is a chronic, low-grade inflammatory disease. We aimed
      to investigate the regulatory effects of erythropoietin (EPO) on the inflammatory
      cytokine production by Muller cells under the condition of DR. The expression
      levels of TNF-alpha, IL-1beta, IL-6 and VEGF in cultured rat Muller cells were
      enhanced by 1 mM glyoxal. The elevated TNF-alpha and IL-1beta, but not IL-6 and
      VEGF, were decreased by 2 U/ml EPO as detected by real-time PCR and ELISA.
      Moreover, the activity of AP-1 but not NF-kappaB was modulated by glyoxal and
      EPO. Intravitreal injection of EPO performed 24 h prior to sacrifice
      significantly reduced TNF-alpha and IL-1beta production while moderately
      attenuating IL-6 and VEGF in the retinas of streptozotocin-induced diabetic rats.
      Furthermore, Muller cells were identified as the main source of IL-1beta
      production as indicated by co-localization of IL-1beta and CRALBP in situ. These
      findings implicate therapeutic potential of EPO in the amelioration of
      inflammation in diabetic retinas.

PMID- 21196301
TI  - Heavy metals nanoparticles in fetal kidney and liver tissues.
AB  - The proliferation of the nanotechnologies with the production of engineered
      nanoparticles presents a dilemma to regulators regarding hazard identification
      mostly for human health. We investigated the presence of inorganic micro and
      nanosized contamination in fetal liver and kidney tissues by Field Emission Gun
      Environmental Scanning Electron Microscope (FEGESEM) innovative observations. An
      observational study in 16 fetuses, complicated (n=8) or not (n=8) by neural tube
      defects, whose mothers obtained the authorization for abortion between 21-23
      weeks of gestation was carried out. Heavy metals concentrations in maternal blood
      were undetectable. FEGESEM assessment showed particles of iron, silicon, aluminum
      and magnesium in different tissues analyzed. The mean size and the number of the
      foreign bodies detected in kidney and liver tissues were higher in NTD fetuses as
      well as the number of total particles (P < 0.05, for all). The present study
      shows first the presence of xenobiotic, nanoscaled contamination, not detectable
      in maternal blood in fetuses. Data are suggestive and open-up a new clue for
      further investigations to elucidate the relationship between pollution at
      nanoscale stage and multiorgan damage.

PMID- 21196302
TI  - Relationship between RANTES and dendritic cells in ovarian cancer patients.
AB  - This study was undertaken to evaluate RANTES levels in the peritoneal fluid (PF)
      and plasma of patients with ovarian cancer (n=73), serous cystadenoma (n=32) or
      normal controls (n=9). RANTES levels were correlated to myeloid and lymphoid
      dendritic cells (DCs). RANTES levels were evaluated using the ELISA assay. DCs
      were quantified using flow cytometry. The PF and plasma RANTES concentrations
      were elevated in the ovarian cancer (OVC) patients when compared to the patients
      with benign tumor (the reference group). Plasma levels of RANTES were higher in
      OVC patients compared with the reference group and with the controls. There were
      no significant differences in the plasma RANTES levels based on tumor stage,
      grade or histology. Women with serous cystadenocarcinoma, clear cell carcinoma
      and endometrioid cystadenocarcinoma had significantly higher PF RANTES levels
      than patients with undifferentiated carcinoma. Women with clear cell carcinoma
      and patients with endometrioid cystadenocarcinoma had higher PF RANTES levels
      than women with mucinous cystadenocarcinoma. We concluded that RANTES production
      in the peritoneal cavities of OVC patients depends on the histological type of
      the tumor cells.

PMID- 21196303
TI  - Development of placenta in a rodent--model for human placentation.
AB  - Rodents provide an excellent experimental model to study human placental
      development. In this review, our aim was to explain major events that underlie
      the placental development in mammals in general, and specifically in rodent.
      Those events include trophoblast cell proliferation, decidual reaction and
      contact between the mesenchyme of the allantois with ectoplacental cone, all
      orchestrated by activation of a series of genes. We also aimed to compare
      molecular and genetic events of rodent and human placentation. Employing the
      rodent placenta development model will yield better understanding of these
      processes in other mammals, especially in humans.

PMID- 21196304
TI  - DNA methyltransferase inhibitor CDA-2 synergizes with high-dose thiotepa and
      paclitaxel in killing breast cancer stem cells.
AB  - It has been suggested that breast cancer stem cells (CSCs), which characterized
      by CD44(+)CD24(-/low), may result in treatment failure in patients with breast
      cancer. It is possible therefore that that inhibiting such subpopulation might
      subsequently improve clinical outcome. In the present study, we found that the
      CD44(+)/CD24(-/low) CSCs, isolated from both human breast cell line MCF-7 and MDA
      MB-231, were more resistant to thiotepa, paclitaxel and anthracycline, when
      compared with the non-breast cancer stem cell subset from the same cell lines,
      whereas the chemosensitivities were remarkably reversed by higher concentration
      of thiotepa and paclitaxel except for adriamycin. The percentage of CSCs was
      significantly decreased with an addition of DNA methyltransferase inhibitor CDA-2
      and the expression of Smo, Shh, and Gli-1 of Hedgehog signaling pathway in CSCs
      was decreased. Of important findings, combination of thiotepa or paclitaxel with
      CDA-2 could significantly inhibit the proliferation of CSCs regardless of their
      dosages. These results unveiled that the selection of cytotoxic agents and
      increasing their dosage might be of great importance in the respect of
      eliminating CSCs. DNA methyltransferase inhibitor CDA-2 exhibited a synergistic
      effect with cytotoxic drugs, which might provide a conceptually new therapeutic
      strategy.

PMID- 21196305
TI  - Shotgun proteomics analysis on maize chloroplast thylakoid membrane.
AB  - In this study we initiated a proteomic investigation of the maize thylakoid
      membrane by using a shotgun proteomic approach based on LC-MS(E). A total of 34
      maize thylakoid membrane proteins were identified, the majority of which are
      primarily involved in photosynthesis, including the light-reaction and carbon
      assimilation. It is noteworthy that all of the core subunits of the Photosystem
      II were identified in our search. Proteins involved in other processes, such as
      iron storage, were also detected in our study. The quantity of each identified
      protein was also determined. Of interest, we discovered that the amount of the
      three ATP synthase subunits were not equivalent, suggesting that these proteins
      perform other functions in addition to ATP synthesis. To our knowledge this is
      the first extensive proteomic investigation of the maize thylakoid membrane, and
      will likely enable further study of maize photosynthesis and chloroplast
      development.

PMID- 21196306
TI  - Isolation and expansion of adipose-derived stem cells for tissue engineering.
AB  - For treatment of cardiac failure with bone marrow-derived mesenchymal stem cells,
      several clinical trials are ongoing. However, more attention is gathering on the
      use of adipose tissue-derived stem cells (ASCs). This paper describes the
      optimization of isolation and propagation of ASCs for subsequent clinical use. In
      the isolation step, several enzymes were compared with respect to yield of
      nucleated cells and precursor cells. Our results showed, that the interdonor
      variablility was greater than differences between individual enzymes. For
      propagation of cells, different types of media, sera and serum replacers were
      evaluated regarding their ability to support cell growth and preserve
      differentiation potential. Most of serum replacers proved inferior to fetal calf
      serum. Among the media tested, modified Eagle's media alpha was superior in
      promoting cell growth while preserving the ability to differentiate. Also, the
      effect of cell seeding density and hypoxic culture was evaluated. In this study,
      we show that it is possible to maximize cell yield regardless of donor individual
      characteristics by simple manipulations of media composition, cell seeding
      density and gaseous environment.

PMID- 21196307
TI  - The state of the art of in vitro fertilization.
AB  - Since the first description of successful human in vitro fertilization in 1978,
      researchers and clinicians have been striving to improve the efficacy and safety
      of the technique. Advances in technology and in our understanding of human
      reproduction have contributed to increased success rates and decreased rates of
      higher order multiple births. However, there is still room for improvement as
      'unexplained infertility' still affects many couples, and the incidence of twin
      pregnancies remains elevated. This review will discuss some of the recent
      advances in the fields of molecular genetics, proteomics and oocyte culture that
      will ultimately enhance the clinical practice of preimplantation genetic
      diagnosis, embryo selection and in vitro maturation. It will also discuss the
      potential for these advances to improve both the safety and efficacy of in vitro
      fertilization in the near future.

PMID- 21196308
TI  - Effects of monosodium glutamate supplementation on glutamine metabolism in adult
      rats.
AB  - Monosodium glutamate (MSG) is a worldwide used flavor enhancer. Supplemental
      glutamate may impact physiological functions. The aim of this study was to
      document the metabolic and physiological consequences of supplementation with 2%
      MSG (w/w) in rats. After 15 days-supplementation and following the ingestion of a
      test meal containing 2% MSG, glutamic acid accumulated for 5h in the stomach and
      for 1h in the small intestine. This coincided with a significant decrease of
      intestinal glutaminase activity, a marked specific increase in plasma glutamine
      concentration and a transient increase of plasma insulin concentration. MSG after
      chronic or acute supplementation had no effect on food intake, body weight,
      adipose tissue masses, gastric emptying rate, incorporation of dietary nitrogen
      in gastrointestinal and other tissues, and protein synthesis in intestinal
      mucosa, liver and muscles. The only significant effects of chronic
      supplementation were a slightly diminished gastrocnemius muscle mass, increased
      protein mass in intestinal mucosa and decreased protein synthesis in stomach. It
      is concluded that MSG chronic supplementation promotes glutamine synthesis in the
      body but has little effect on the physiological functions examined.

PMID- 21196309
TI  - Surfactant proteins A and D in pregnancy and parturition.
AB  - Surfactant proteins A and D have extra-pulmonary expression at various mucosal
      sites including the reproductive tract. Reproductive tissues require a fine
      immune balance, strong enough to keep infection at a bay and at the same time,
      subtle enough to support an allogeneic fetus throughout the pregnancy. Roles of
      SP-A and SP-D have been studied in depth and include immunoregulatory function,
      besides strengthening the innate immune system against various pathogens in the
      lungs. Interestingly, levels of SP-A and SP-D in the amniotic fluid increase
      progressively in pregnancy. SP-A has been implicated in the induction of
      parturition. The present review elaborates the plausible roles of SP-A and SP-D
      in pregnancy maintenance and future applications.

PMID- 21196310
TI  - Efficacy of Cordyceps sinensis in long term treatment of renal transplant
      patients.
AB  - High doses of cyclosporin A (CsA) can not be used in the long term treatment of
      kidney allograft recipients primarily due to severe side effects. In the present
      study, we investigated the potential application of Cordyceps sinensis (CS) in
      the long term treatment of renal transplant patients. The renal function and
      survival rates of grafts and patients did not show significantly different
      between the control group and the treatment group. However, the incidences of
      complications were significantly lower in the treatment group compared with that
      in control group with the exception of those showing acute rejection.
      Furthermore, the dosage and the whole blood trough concentrations of CsA were
      significantly lower than control group. However, there was no significant
      difference in the serum level of IL-2 in the two groups. Interestingly, the serum
      level of IL-10 in the treatment group was significantly higher than that in
      control group. These data demonstrat that CS may be used in combination with a
      low dose of CsA in the long term treatment of kideny transplant patients.

PMID- 21196311
TI  - Alterations of primary fatty acid amides in serum of patients with severe mental
      illness.
AB  - Cannabis consumption is a well known risk factor for the onset of schizophrenia
      and evidence accumulates that the endocannabinoid system may play a central role
      in the disease etiology. Using a clinical bioinformatics approach, we have
      previously found primary fatty acid amides, which are linked to the
      endocannabinoid system, to be elevated in drug naive schizophrenia and affective
      disorder. Here, we provide a detailed description of these findings and expand
      the investigation by analyzing serum from 74 patients after short term treatment
      with antipsychotic medication using a liquid chromatography-mass spectrometry (LC
      MS) metabolomics approach. We show that primary fatty acid amide (pFAA) levels
      normalize after treatment with typical but not after treatment with atypical
      antipsychotic medication. Also, the comparison of pFAA levels in schizophrenia
      patients to those of sleep deprived healthy volunteers suggests that pFAA
      abnormalities were not related to changes in the sleep architecture of patients
      with mental illness. Our findings support the involvement of the endocannabinoid
      system in the pathology of schizophrenia.

PMID- 21196312
TI  - Respiratory chain complex I is a mitochondrial tumor suppressor of oncocytic
      tumors.
AB  - Oncocytic tumors, also called oxyphilic tumors, are characterized by
      hyperproliferation of mitochondria, which histologically presents as a fine
      granular eosinophilic cytoplasm. In accordance with the high mitochondrial
      density in oncocytomas, transcript levels of subunits of complexes of the
      oxidative phosphorylation (OXPHOS) system are increased. Hence, for a long time
      oncocytomas were presumed to have a highly active aerobic mitochondrial energy
      metabolism. Recently, detailed analysis of all OXPHOS complexes in a variety of
      oncocytomas revealed loss of complex I and compensatory up-regulation of the
      other complexes. In half of the oncocytoma cases examined the absence of complex
      I is caused by disruptive mutations in mitochondrial DNA encoding complex I
      subunits. The new data presented here on rare oncocytomas and the accompanying
      review of the literature clearly indicate that complex I deficiency in
      combination with up-regulation of mitochondria can be regarded as a hallmark of
      oncocytic tumor cells. Therefore, complex I of the respiratory chain has to be
      added to the growing list of mitochondrial tumor suppressors.

PMID- 21196314
TI  - TNF-alpha mediated NF-kappaB activation is constantly extended by
      transglutaminase 2.
AB  - Increased levels of transglutaminase 2 (TGase 2) expression have been reported in
      many inflammatory diseases, as well as in drug resistant cancer cells. Previous
      reports have shown that TGase 2 is capable of inducing nuclear factor-kappaB (NF
      kappaB) activation via depletion of inhibitor of kappaB (I-kappaB)alpha through
      polymerization in the absence of I-kappaBalpha kinase activation. This raises the
      question of whether increased expression of TGase 2 can extend NF-kappaB
      activation mediated by a canonical activation pathway. In the TGase 2-inducible
      EcR23/TG cell line, TGase 2 over-expression resulted in sustained activation of
      NF-kappa B in the presence of TNF-alpha, for up to 24 hrs, while in the absence
      of TGase 2 induction, NF-kappaB activity was restored to basal levels within 6
      hrs of TNF-alpha treatment. In mice injected with an adenovirus vector expressing
      TGase 2, NF-kappaB was constitutively activated for up to 5 days, whereas
      Adeno/GFP-injected mice exhibited attenuated activation of NF-kappaB in response
      to TNF-alpha stress. Thus, the presence of increased levels of TGase 2 may
      exacerbate NF-kappa B activation in inflammatory states.

PMID- 21196313
TI  - The effect of coptis chinensis on the signaling network in the squamous carcinoma
      cells.
AB  - The effects of Coptis chinensis on the behavior of squamous cell carcinoma have
      not yet been established. We examined the anticancer activity of Coptis chinensis
      on human squamous carcinoma cells, both in vitro and in xenografted nude mice,
      and applied Pathway Array Technology to understand possible involvement of
      signaling pathways in Coptis Chinensis induced tumor cells inhibition as well.
      Following Coptis chinensis treatment, a time-dependent reduction in proliferation
      was observed in both cell lines and NCR/NU mice. Coptis chinensis has a wide
      effect on cell signaling, including cell cycle regulation (Cdk6, Cdk4, cyclin B1,
      cyclin E, cyclin D1, p27), cell adhesion (E-cadherin, osteopontin),
      differentiation, apoptosis(p-Stat3, p53, BRCA1), cytoskeleton (p-PKC alpha/beta
      II, Vimentin, p-PKCalpha), MAPK signaling (raf-1, ERK1/2, p-p38, p-ERK), and the
      phosphatidylinositol 3-kinase signaling pathway (p-Akt, Akt, p-PTEN). In our
      conclusions, Coptis chinensis may be a novel therapeutic drug for squamous cell
      carcinoma.

PMID- 21196315
TI  - Spatiotemporal expression of D10Wsu52e in the developing mouse pancreas.
AB  - D10Wsu52e is a recently discovered and highly conserved mouse gene. FAAP, the
      protein encoded by D10Wsu52e, participates in regulation of integrin-based focal
      adhesions. To explore the function of FAAP in pancreas development, we assessed
      the spatiotemporal expression of D10Wsu52e, paxillin and vinculin in the
      developing mouse pancreas through quantitative RT-PCR, in situ hybridization and
      histochemistry methods. Our results show that, at e9.5 and e10.5, D10Wsu52e mRNA
      is mainly expressed in the brain, optic vesicles, otic vesicles, limb buds,
      somites and gut, and also in the pancreatic buds at e10.5. Subsequently,
      D10Wsu52e mRNA is expressed mainly in the epithelial progenitors at e12.5, then
      decreases in the endocrine precursors and ductal cells, whereas still maintains
      in the exocrine precursors until e15.5. At e17.5, D10Wsu52e mRNA is highly
      expressed in exocrine acinar cells, but weakly in ductal and endocrine cells.
      Furthermore, the expression patterns of paxillin and vinculin mRNAs are similar
      to D10Wsu52e from e12.5 to e15.5, which suggests that D10Wsu52e may be related to
      the acinar development, adhesion and migration of progenitors and endocrine
      precursors.

PMID- 21196316
TI  - Pharmacogenetics of bisphosphonate-associated osteonecrosis of the jaw.
AB  - An undesirable effect associated with bisphosphonates is osteonecrosis of the jaw
      (ONJ). Case reports discussed ONJ development in patients with multiple myeloma
      or metastatic cancers receiving bisphosphonates as palliation for malignant bone
      disease. No causative relationship has been unequivocally demonstrated between
      ONJ and bisphosphonate therapy. To determine if a higher sensitivity to
      bisphosphonates could in part explain the development of ONJ, the segregation of
      A/C rs2297480 polymorphism of gene encoding for the farnesyl pyrophosphate
      synthase (FDPS) with ONJ was evaluated in a cohort of 68 Caucasian patients
      treated with zoledronic acid for multiple myeloma and metastatic mammary and
      prostate cancer. The AA and CC genotypes were highly differently distributed
      among ONJ patients and controls, matched for sex and type of malignant disease,
      with a positive correlation between AA carrier status and occurrence of ONJ
      (p=0.03) after 18-24 months of treatment. Because FDPS gene variants have been
      associated with bone morbidity, these pharmacogenetic association likely reflect
      the interaction of amino-bisphosphonates with germline sensitivity to drug
      actions, and might identify patients at highest risk to develop ONJ.

PMID- 21196317
TI  - Bone marrow-derived microglia in pilocytic astrocytoma.
AB  - Tumour associated macrophages (TAMs) are increasingly recognized as supporters of
      tumour growth. The present study was undertaken to examine benign pilocytic
      astrocytomas (PAs) for the presence of M2 macrophages. We have asked the question
      whether TAMs in PAs share the predominant CD163 immunophenotype with tumour
      associated microglia/macrophages of malignant gliomas. In addition, we were
      interested in the question whether there is evidence that the macrophages in PAs
      derive from resident microglia in surrounding normal brain or whether cells
      expressing a macrophage phenotype may invade PAs from the vasculature. The latter
      question is of great interest with regard to so-called "bone marrow-derived
      microglia" (BMDM) which may provide a physiological route of entry into the CNS
      that could be used for novel cell-based treatments of brain cancer. In fact, we
      have found strong morphological evidence for such macrophage recruitment into
      PAs. We propose therefore that PAs may be used as a model for the study of
      macrophage recruitment into gliomas. Importantly, our results also confirm that
      microglia/macrophage infiltration per se is not associated with malignant glioma
      behaviour.

PMID- 21196318
TI  - Hepatitis D antigens cause growth retardation and brood-size reduction in C.
      elegans.
AB  - Caenorhabditis elegans is a model organism that has been used to study human
      bacterial and viral pathogenesis. We report here the expression of human
      hepatitis delta viral antigens (HDAg) in C. elegans and measure the effect on the
      sterility, growth, and brood size in transgenic worms. Expression of HDAg under
      two different promoters, fib-1 (a ubiquitous promoter) and myo-2 (a pharynx
      specific promoter), was achieved in C. elegans using dicistronic or tricistronic
      vectors derived from the operon CEOP5428. Transgenic worms expressing HDAg
      ubiquitously resulted in 20% to 70% sterility while those expressing HDAg in the
      pharynx displayed 70% sterility. Most of worms expressing HDAg in pharynx were
      arrested at larvae stage 2 or 3 and displayed a 70% reduction in brood size.
      Domain mapping experiments suggested that the nuclear localization signal of HDAg
      is required for the observed effect. Heat-shock induction of HDAg expression
      revealed that L4 larvae were the most sensitive to brood size reduction. These
      studies demonstrate that C. elegans can provide an additional model for studying
      HDAg interactions with host targets.

PMID- 21196319
TI  - Cancer metastasis, challenges, progress and the opportunities.
AB  - The spread of cancer cells in the body -'metastasis,' is a challenging issue for
      cancer patients and for cancer research. From a clinical point of view, the
      majority of the cancer-related deaths in patients who suffer from solid cancers
      are metastasis-related. Although this life threatening consequence in cancer is
      recognised almost immediately at the time of diagnosis, the current-state-of
      knowledge on the mechanisms and effective ways to combat cancer metastasis in
      clinical settings is far from being realized. Thus, making the necessity of
      continuing research into cancer metastasis evermore demanding and critical. This
      issue of the journal is directed toward consideration of some of the salient
      aspects of cancer metastasis, with a focus on recent progress of the molecular
      and cellular mechanisms of cancer invasion and metastasis.

PMID- 21196321
TI  - Sage components enhance cell death through nuclear factor kappa-B signaling.
AB  - The sage components linalyl acetate (Ly) and alpha-terpineol (Te) exhibit
      synergistic anti-proliferative effects. We investigated the effects of Ly and Te
      on NF-kappaB signaling in HCT-116 colon cancer cells. Ly and Te combinations dose
      dependently reduced HCT-116 viability at non-cytotoxic concentrations.
      Combination treatment induced 30%-60% increase in PreG1 through induction of
      apoptosis and necrosis. DNA binding assays revealed that combination treatment
      suppressed both basal and TNF-alpha-induced NF-kappaB activation. This
      suppression correlated with the inhibition of p65 nuclear translocation and
      IkappaB-alpha degradation. The lack of change in IKK expression levels or
      inhibition in IkappaB-alpha phosphorylation suggest the involvement of an IKK
      independent mechanism. Ly and Te combination was found to downregulate the
      expression of NF-kappaB-regulated antiapoptotic and proliferative gene products.
      Separate treatments and drug combinations significantly decreased DNA binding
      activity of NF-kappaB which led to the potentiation of cell death induced by the
      colon cancer drugs oxaliplatin and 5-FU. These results indicate that Ly and Te
      anticancer activities are partly mediated through the suppression of NF-kappaB
      activation, suggesting their use in combination with chemotherapeutic agents to
      induce apoptosis.

PMID- 21196320
TI  - The respiratory-dependent assembly of ANT1 differentially regulates Bax and Ca2+
      mediated cytochrome c release.
AB  - The adenine nucleotide translocator (ANT) is a control point of several
      fundamental cell processes, as diverse as cell energy supply, mitochondrial DNA
      maintenance, and apoptosis. This paper describes six individual structures of the
      carrier, distinguished according to ANT1 oligomeric and conformational states, as
      well as associations with other proteins. Transitions between these structures
      depend on energy demand and thus contribute to a metabolic reserve of oxidative
      phosphorylation (OXPHOS) activity. Moreover, at low respiratory chain activity,
      we demonstrate that, unlike a mitochondrial Ca2+ upload, Bax, a pro-apoptotic Bcl
      2-family protein, is able to trigger a massive release of cytochrome c from one
      of these ANT1 structures. These new insights emphasize the close relationship
      between structural rearrangements of ANT and molecular apoptotic events at
      distinct cell energy levels. OXPHOS functioning has to therefore be considered a
      crucial control point for the events leading to these contrasting pathways.

PMID- 21196323
TI  - NAD+ treatment decreases tumor cell survival by inducing oxidative stress.
AB  - NAD+ plays important roles in various biological processes. It has been shown
      that NAD+ treatment can decrease genotoxic agent-induced death of primary
      neuronal and astrocyte cultures, and NAD+ administration can reduce ischemic
      brain damage. However, the effects of NAD+ treatment on tumor cell survival are
      unknown. In this study we found that treatment of NAD+ at concentrations from 10
      micromolar to 1 mM can significantly decrease the survival of various types of
      tumor cells such as C6 glioma cells. In contrast, NAD+ treatment did not impair
      the survival of primary astrocyte cultures. Our study has also indicated that
      oxidative stress mediates the effects of NAD+ on the survival of tumor cells, and
      P2X7 receptors and altered calcium homeostasis are involved in the effects of
      NAD+ on the cell survival. Collectively, our study has provided the first
      evidence that NAD+ treatment can decrease the survival of tumor cells by such
      mechanisms as inducing oxidative stress. Because NAD+ treatment can selectively
      decrease the survival of tumor cells, NAD+ may become a novel agent for treating
      cancer.

PMID- 21196322
TI  - MYCN, neuroblastoma and focal adhesion kinase (FAK).
AB  - Neuroblastoma is the most common extracranial solid tumor of childhood. This
      tumor is characterized by poor survival, especially when it features
      amplification of the MYCN oncogene. The ability for human cancers to propagate is
      marked by their ability to invade and metastasize to distant sites. Focal
      adhesion kinase (FAK) is a key tyrosine kinase involved in the survival and
      metastasis of a number of human tumor types. We have shown that FAK is present in
      human neuroblastoma and that its expression in neuroblastoma is related to the
      MYCN oncogene. We have also demonstrated that inhibition of FAK in neuroblastoma
      leads to decreased tumor cell survival. The current review addresses the
      relationship between the MYCN oncogene, focal adhesion kinase and neuroblastoma.

PMID- 21196324
TI  - Obesity in pregnancy: problems and potential solutions.
AB  - Recent years have witnessed an increase in the prevalence of maternal obesity
      during pregnancy in the United States and worldwide. Obese women have increased
      risks for gestational problems, such as diabetes, hypertension, and pre
      eclampsia. Further, gestational obesity can adversely impact fetal growth and
      result in macrosomia, congenital abnormalities, and even fetal death. Measures
      must be taken to reduce maternal adiposity, as even a modest weight loss during
      pregnancy is beneficial for the health of mothers and fetus. Calorie restriction
      and moderate exercise are proven safe methods of stopping weight gain and/or
      inducing white-fat loss in these subjects. Additionally, therapeutic drugs that
      activate the AMP-activated protein kinase signaling pathway may be effective in
      ameliorating pathological conditions in obese patients. Finally, dietary
      supplementation with L-arginine or its effective precursor (L-citrulline) may be
      beneficial for managing overweight or obese gestating women by reducing white-fat
      accretion. Because of ethical concerns over human studies, animal models (e.g.,
      sheep, pigs, baboons, rats, and mice) are warranted to test novel hypotheses with
      enormous biological significance and clinical applications.

PMID- 21196325
TI  - HIV-1 integration site preferences in pluripotent cells.
AB  - HIV-1-based vectors are widely used in gene therapy. In somatic cells, these
      vectors mainly integrate within genes. However, no distinct integration site
      preferences have been observed with regard to large chromosomal regions. The
      recent emergence of induced pluripotent stem (iPS) cells, similar to embryonic
      stem (ES) cells, has raised questions about where integration occurs in these
      cells. In this work we investigated the integration site preferences of HIV-1
      based vectors in a pluripotent, ES-like cell line. We show that approximately 30%
      of the integrations occur in the vicinity of telomeres. We have analyzed
      integration sites in various somatic cells, as reported by us and other groups,
      and observed that this integration pattern is unique to the analyzed pluripotent
      cell line. We conclude that pluripotent cells may contain distinct cellular
      cofactors that participate in integration targeting and that are not present in
      somatic cells.

PMID- 21196326
TI  - A new bone surgical laser technique: technical aspects and applications in
      dentistry.
AB  - Ten patients requiring the extraction of a severely-deteriorated molar or
      premolar before placement of a dental implant for prosthodontic rehabilitation
      were selected (6 women; 4 men). The sockets were curetted and decontaminated with
      an 810 nm wavelength diode laser using a 400 micron fiber at close distance (1
      mm) from the target area, power setting 2.5 W, pulsed mode (10 msec t-on, 10 msec
      t-off for five seconds, three repetitions for each bone wall, 30 seconds pause
      between each irradiation). The socket filled with beta-TCP plus Tissucol and
      primary closure was attempted. In addition all patients were treated with a 810
      nm GaAlAs laser, in continuous wave mode, defocused hand-piece, 50 J?cm2 ( 1W for
      50 seconds) after surgery and on days 3, 5, 7 postoperatively. At 18 months after
      prosthodontic treatment and loading, the implant was stable. Laser therapy,
      combined with a graft of biomaterial composed of beta-TCP and tissucol, prevented
      alveolar crest resorption following tooth extraction. Formation of new bone of
      acceptable quality and quantity permitted placement of osseointegrated dental
      implants.

PMID- 21196328
TI  - Multi-confocal fluorescence correlation spectroscopy.
AB  - We report a multi-confocal Fluorescence Correlation Spectroscopy (mFCS) technique
      that combines a Spatial Light Modulator (SLM), with an Electron Multiplying-CCD
      camera (EM-CCD). The SLM is used to produce a series of laser spots, while the
      pixels of the EM-CCD play the roles of virtual pinholes. The phase map addressed
      to the SLM, calculated by using the spherical wave approximation, makes it
      possible to produce several diffraction limited laser spots. The fastest
      acquisition mode leads to a time resolution of 100 microseconds. By using
      solutions of sulforhodamine G we demonstrated that the observation volumes are
      similar to that of a standard confocal set-up. mFCS experiments have also been
      conducted on two stable cell lines: mouse embryonic fibroblasts expressing eGFP
      actin and H1299 cells expressing the heat shock factor fusion protein HSF1-eGFP.
      In the first case we could recover the diffusion constant of G-actin within the
      cytoplasm, although we were also sensitive to interactions with F-actin.
      Concerning HSF1, we could clearly observe the modifications of the number of
      molecules and of the HSF1 dynamics during heat shock.

PMID- 21196327
TI  - Sodium thiosulfate exposure disrupts in vitro and in vivo heart development.
AB  - It is well-known that the majority of malformations found in the human population
      is based on complex gene-environment interactions. As an industrial chemical
      sodium thiosulfate (STS) is used heavily in many industries. Nevertheless, there
      is little known about the effects of STS on embryo development. In the present
      study, we have investigated the effects of STS on cardiac development in rat
      cardiomyocyte H9C2 cell line and chick embryos. As determined by MTT assays, the
      proliferation of H9C2 cells was inhibited by STS in a dose-dependent manner.
      Fertilized eggs injected via the yolk sac with STS at Hamburger-Hamilton (HH)
      stages 6, 9 and 12 showed significantly increased cardiotoxicity at HH stage 18,
      including cardiomyocyte apoptosis and animal mortality. Western blot analysis
      showed that STS significantly affected the expression of the apoptosis-related
      genes bcl-2, bax, and caspase-3 in a dose-dependent manner in the H9C2 cell line
      and in chick embryos. Dysregulation of apoptosis was correlated with embryonic
      heart malformations. Thus, STS may be a potent cardiac teratogen during embryo
      development.

PMID- 21196329
TI  - Global analysis of autocorrelation functions and photon counting distributions.
AB  - In fluorescence correlation spectroscopy (FCS) and photon counting histogram
      (PCH) analysis the same experimental fluorescence intensity fluctuations are
      used, but each analytical method focuses on a different property of the signal.
      The time-dependent decay of the correlation of fluorescence fluctuations is
      measured in FCS yielding, for instance, molecular diffusion coefficients. The
      amplitude distribution of these fluctuations is calculated by PCH yielding the
      molecular brightness. Both FCS and PCH give information about the molecular
      concentration. Here we describe a global analysis protocol that simultaneously
      recovers relevant and common parameters in model functions of FCS and PCH from a
      single fluorescence fluctuation trace. The global analysis approach is described
      and tested with experimental fluorescence fluctuation data of enhanced green
      fluorescent protein (eGFP) and dimeric eGFP (two eGFP molecules connected by a
      six amino acid long linker) in aqueous buffer. Brightness values and diffusion
      constants are recovered with good precision elucidating novel excited-state and
      motional properties of both proteins.

PMID- 21196330
TI  - Safety and efficacy of bone marrow-derived autologous CD133+ stem cell therapy.
AB  - The Phase I clinical study was designed to assess the safety and feasibility of a
      dose escalating intracoronary infusion of autologous bone marrow (BM)-derived
      CD133+ stem cell therapy to the patients with chronic total occlusion (CTO) and
      ischemia. Nine patients were received CD133+ cells into epicardial vessels
      supplying collateral flow to areas of viable ischemic myocardium in the
      distribution of the CTO. There were no major adverse cardiac events (MACE),
      revascularization, re-admission to the hospital secondary to angina, or acute
      myocardial infarction (AMI) for the 24-month period following cellular infusion.
      In addition, there were no periprocedural infusion-related complications
      including malignant arrhythmias, loss of normal coronary blood flow or acute
      neurologic events. Cardiac enzymes were negative in all patients. There was an
      improvement in the degree of ischemic myocardium, which was accompanied by a
      trend towards reduction in anginal symptoms. Intracoronary infusion of autologous
      CD133+ marrow-derived cells is safe and feasible. Cellular therapy with CD133+
      cells to reduce anginal symptoms and to improve ischemia in patients with CTO
      awaits clinical investigation in Phase II/III trials.

PMID- 21196332
TI  - Risk of carcinoma in women with ovarian endometrioma.
AB  - Endometriosis affects an estimated 10% of women in the reproductive-age group.
      Here, we review current knowledge on molecular genesis of endometriosis
      associated epithelial ovarian carcinoma (EOC). This article reviews the English
      language literature for biology, pathogenesis, and pathophysiological studies on
      endometriosis-associated EOC. Although endometriosis generally remains a benign
      condition, it demonstrates somatically acquired genetic alterations. Clear cell
      carcinoma (CCC) and endometrioid adenocarcinoma (EAC) are the most frequent types
      of EOC associated with endometriosis. Retrograde menstruation or ovarian
      hemorrhage carries highly pro-oxidant factors, such as iron, into the peritoneal
      cavity or ovarian endometrioma. CCC and EAC should be considered separately in
      studies of endometriosis-associated EOC. The repeated events of hemorrhage in
      endometriosis can contribute to carcinogenesis and progression via 3 major
      processes: 1) increasing oxidative stress promotes DNA methylation; 2) activating
      anti-apoptotic pathways supports tumor promotion; and 3) aberrant expression of
      stress signaling pathways contributes to tumor progression. This review
      summarizes recent advances in the understanding of epidemiology, carcinogenesis,
      pathogenesis, and pathophysiology of endometriosis-associated EOC; and a possible
      novel model is proposed.

PMID- 21196333
TI  - Therapeutic approaches targeting tumor vasculature in gastrointestinal cancers.
AB  - Antiangiogenic therapy, especially anti-vascular endothelial growth factor (VEGF)
      antibody therapy, has become an important treatment option for the management of
      a number of human malignancies including some gastrointestinal tumors. However,
      there have been many cases of resistance observed against anti-VEGF antibody
      treatment. As to the first reason, some types of advanced colon cancers do not
      upregulate VEGF. As to the second reason, not a few malignancies will acquire
      phenotypic resistance to VEGF or its receptors after anti-VEGF antibody therapy.
      The molecular and cellular mechanisms associated with the resistance to VEGF
      targeted agents are not fully understood. Better understanding of the mechanisms
      and improvement of antiangiogenic regimens to overcome drug resistance would help
      in the selection of those patients who are more likely to benefit from VEGF
      targeted therapy. Other possible applications of anti-VEGF antibody include
      chemoprevention of cancer progression. It is well known that angiogenic switch
      and upregulation of angiogenic cascades are essential for cancer development.
      Therefore, prophylatic application of anti-VEGF antibody before angiogenic switch
      may inhibit aggressive growth of these malignancies at an initial phase.

PMID- 21196331
TI  - Sulforaphane synergizes with quercetin to inhibit self-renewal capacity of
      pancreatic cancer stem cells.
AB  - According to the cancer stem cell hypothesis, the aggressive growth and early
      metastasis of cancer may arise through dysregulation of self-renewal of stem
      cells. The objectives of this study were to examine the molecular mechanisms by
      which sulforaphane (SFN, an active compound in cruciferous vegetables) inhibits
      self-renewal capacity of pancreatic cancer stem cells (CSCs), and synergizes with
      quercetin, a major polyphenol and flavonoid commonly detected in many fruits and
      vegetables. Our data demonstrated that SFN inhibited self-renewal capacity of
      pancreatic CSCs. Inhibition of Nanog by lentiviral-mediated shRNA expression
      enhanced the inhibitory effects of sulforaphane on self-renewal capacity of CSCs.
      SFN induced apoptosis by inhibiting the expression of Bcl-2 and XIAP,
      phosphorylation of FKHR, and activating caspase-3. Moreover, SFN inhibited
      expression of proteins involved in the epithelial-mesenchymal transition (beta
      catenin, vimentin, twist-1, and ZEB1), suggesting the blockade of signaling
      involved in early metastasis. Furthermore, the combination of quercetin with SFN
      had synergistic effects on self-renewal capacity of pancreatic CSCs. These data
      suggest that SFN either alone or in combination with quercetin can eliminate
      cancer stem cell-characteristics.

PMID- 21196335
TI  - The possible role of fungal contamination in sick building syndrome.
AB  - The following is a review of some of the work that we have done since 2007
      regarding the importance of molds in the phenomenon of sick building syndrome
      (SBS). In these studies we first examined mold contamination in air handling
      units (AHU). Our results showed that Cladosporium sp. were commonly recovered in
      AHU as growth sites and free spores. They were found mainly on the blower wheel
      fan blades, the ductwork, and cooling coil fans. Our results showed that the
      presence of species of molds other than Cladosporium in locations other than the
      blower wheel blades indicated that the AHU condition was not optimal. In a series
      of three papers, we examined growth and mycotoxin production by Chaetomium
      globosum (CG). In these studies we showed that CG produces two potent mycotoxins,
      chaetoglobosin A (Ch-A) and chaetoglobosin C (Ch-C) when grown on building
      material. We discovered that these toxins break down when exposed to temperatures
      in excess of 75 degrees C. We also showed that growth and mycotoxin production by
      CG is favored at a neutral pH. In another study, we showed that mycotoxins can be
      detected in body fluids and human tissues from patients exposed to mycotoxin
      producing molds, and we showed which human tissues or fluids were the most likely
      to give positive results for detection of these compounds. Finally, we showed
      that the macrocyclic trichothecene mycotoxins (MTM) produced by Stachybotrys
      chartarum (SC) are detectable in experimental animals soon after exposure and we
      described the dynamics of MTM tissue loading.

PMID- 21196334
TI  - Complexity of tumor vasculature and molecular targeting therapies.
AB  - Malignant solid tumors require blood supply for their uncontrollable progression.
      Angiogenic blood vessels generally sprout from preexisting vascular cells. In
      addition, various types of precursor cells also participate in tumor
      neovascularization. They include endothelial progenitor cells, hematopoietic stem
      cells and mesenchymal stem cells that are stimulated and attracted into tumor
      lesion, in which a wide variety of proinflammatory factors are involved. Among
      key molecules, vascular endothelial growth factor (VEGF) works as a mastermind
      regulator. Humanized monoclonal antibodies targeting VEGF-mediated signaling
      pathways are currently used as the most pervasive drugs in several types of
      progressive tumors. Adverse effects of these drugs include hypertension and
      proteinuria. Such symptoms are widely observed in preeclamptic patients whose
      blood contain high amount of natural VEGF antagonist. Vasoactive G protein
      coupled receptors (GPCRs)-mediated signalings such as renin-angiotensin system
      and chemokine axes are also noticed that they may become effective therapeutic
      targets. In this review, we discuss general view of angiogenic microenvironment
      in solid tumors, and highlight several key signaling molecules and inhibitory
      effects of them on the whole system.

PMID- 21196336
TI  - 5-azacytidine enhances proliferation in transplanted rat fetal epiglottis.
AB  - Fetal rat epiglottis and its developmental potential in ectopic transplants under
      the influence of the epigenetic drug was investigated. Epiglottises from 17-days
      old rat embryos were transplanted under kidney capsules of adult rats for 14
      days. 5-azacytidine (5 mg/kg) was injected intraperitoneally during first three
      days and controls were sham treated. TEM, immunohistochemical detection and
      quantitative stereological analysis of the Proliferating Cell Nuclear Antigen
      (PCNA) expression (numerical density N(v)) were performed. Typical chondroblasts
      with long surface processes and sparse lipid droplets were found in fetal
      epiglottis and chondrocytes with shorter processes, numerous lipid droplets and
      elastic fibers in adult. PCNA was expressed in almost all cells of the fetal
      epiglottis while in the adult it was expressed in minority of cells. In
      transplants, differentiation progressed towards the differentiation found in the
      adult. Application of 5-azacytidine increased the capacity for proliferation (N(v
      PCNA)) in comparison to controls but no difference in differentiation was
      observed. Data about the developmental potential and induction of proliferation
      in mammalian epiglottis by epigenetic modulation is of importance for
      regenerative medicine.

PMID- 21196337
TI  - The role of nuclear factor-kappa-B p50 subunit in the development of
      endometriosis.
AB  - p50 is a member of the NF-kappaB family known to be involved in endometriosis. To
      gain insight into the roles of p50 in the development of endometriosis, we cross
      transplanted endometrial fragments from p50 knockout mice to wild-type mice and
      vice versa, and also autotransplanted the fragments within the knockout and wild
      type mice, inducing endometriosis. We then evaluated the size of the endometrial
      implants, and immunoreactivity to phosphorylated p65 (p-p65), PKCepsilon and
      TRPV1 in ectopic and eutopic endometrium as well as in vagina. We found that p50
      deletion significantly reduces the size of endometrial implants. The
      immunoreactivity to p-p65 and PKCepsilon, but not TRPV1, was reduced in
      endometrial implants in p50 knockout mice. Deletion of p50 significantly reduced
      p-p65 and PKCepsilon, but not TRPV1, expression in eutopic endometrium and
      vagina. It also disrupts NF-kappaB activation and PKCepsilon expression in
      eutopic and vagina, suggesting the role of NF-kappaB in regulating PKCepsilon,
      which plays an important role in nociception. These data show that p50 is
      involved in the development of endometriosis and may be a promising therapeutic
      target.

PMID- 21196338
TI  - Sevoflurane preconditioning confers neuroprotection via anti-inflammatory
      effects.
AB  - Neuroprotection afforded by volatile anesthetic preconditioning (APC) has been
      demonstrated in both in vivo and in vitro experiments, yet the underlying
      mechanism is poorly understood. We therefore investigated whether suppression of
      p38 MAPK, NF-kappa B and the downstream pro-inflammatory signaling cascade
      contribute to sevofurane APC-induced neuroprotection. Male Sprague-Dawley rats
      were exposed for 30 min/day on 4 consecutive days to ambient air or to
      sevoflurane (1.2% or 2.4%). Then rats were subjected to filament occlusion of the
      middle cerebral artery (MCAO) for 60 min, and euthanized 3 days after MCAO for
      measuring infarct volume. APC with sevofurane markedly improved neurological
      performance of stroke rats, significantly decreased infarct volume, and robustly
      suppressed activation of NF-kappa B and p38 MAPK, and expression of inflammatory
      cytokines. Furthermore, APC with sevofurane showed a direct inflammation
      suppressing effect in rat brain receiving intracerebroventricular infusion of a
      dose of LPS that doesn't cause overt brain damage. Thus, the data suggest that
      APC with sevoflurane confers neuroprotection against focal ischemic brain injury,
      at least in part, by the anti-inflammatory effects of sevoflurane.

PMID- 21196339
TI  - Molecular alterations of E-cadherin and beta-catenin in brain metastases.
AB  - The molecular mechanisms and candidate genes involved in metastasis to the brain
      need elucidation. In the present study brain metastases were analyzed regarding
      changes of E-cadherin (CDH1) and beta-catenin (CTNNB1). Loss of heterozygosity
      (LOH) of the CDH1 gene was detected in 42.2% of samples. The highest frequency of
      LOHs was observed in metastases from primary sites of lung adenocarcinoma and
      small cell lung cancer. Metastases from breast and colon demonstrated changes in
      55.6% and 50% of cases. Downregulation of E-cadherin protein was observed in 83%
      of samples. Only 21.1% of samples with E-cadherin LOH had beta-catenin located in
      the nucleus. Image analysis showed that the quantities of E-cadherin and beta
      catenin were significantly positively correlated (P = 0.008). Changes of E
      cadherin were frequent in brain metastases that we investigated. Lack of
      mutations of beta-catenin, the fact that it was not frequently found in the
      nucleus and the positive correlation between the two proteins may suggest that
      the break-up of adherens junctions, and not the activation of wnt signaling, is
      responsible for metastasis formation.

PMID- 21196340
TI  - STICS, SCOUTs and p53 signatures; a new language for pelvic serous
      carcinogenesis.
AB  - The events leading to the most common and most lethal ovarian carcinoma - high
      grade serous carcinoma - have been poorly understood. However, the detailed
      pathologic study of asymptomatic women with germ-line BRCA 1 or BRCA2 (BCRA+)
      mutations has unearthed an early malignancy, serous tubal intraepithelial
      carcinomas (STIC), which has linked many peritoneal and ovarian serous carcinomas
      to the fimbria. The distinction between high-grade serous and endometrioid
      carcinomas continues to narrow, with shared alterations in expression of pTEN,
      PAX2 and p53. Moreover, the discovery of clonal alterations in p53 in benign
      tubal epithelium, - p53 signatures - has established a foundation for a serous
      cancer precursor in the fimbria. We have expanded this concept to include a
      generic secretory cell outgrowth (SCOUT) in the fallopian tube that is associated
      with altered PAX2 expression. As the repertoire of gene alterations is expanded
      and its link to serous carcinogenesis clarified, a cogent pathway to high-grade
      Mullerian carcinomas will emerge. This will challenge conventional thinking about
      ovarian carcinogenesis but will provide a new template for studies of ovarian
      cancer prevention.

PMID- 21196341
TI  - Alternatives to heart transplantation: integration of biology with surgery.
AB  - Chronic heart failure is one of the major health care issues in terms of
      increasing number of patients, rate of hospitalizations and costs. Heart
      transplantation is the best established therapy for patients with severe heart
      failure. However, the number of donors limits the activity to 5000 heart
      transplants performed annually worldwide. This limitation has generated
      alternative treatments. The increase of the interest in the reversibility of the
      heart failure and the application of new biological alternatives has generated
      therapeutic strategies designed to integrate biology and medical technologies in
      order to act to the biomechanical, the molecular and the neurohormonal mechanisms
      of heart failure. These treatments include cellular cardiomyoplasty, tissue
      engineering, surgical left ventricular restoration as well as passive and active
      mechanical ventricular assistance as destination therapy, bridge to recovery or
      bridge to transplantation. The integrated development of these approaches could
      offer hopeful treatments, although there is still much to be learned regarding
      the optimal use of these strategies.

PMID- 21196342
TI  - Apoptosis and endometriosis.
AB  - Apoptosis is a distinctive form of programmed cell death resulting in the
      efficient elimination of cells without eliciting an inflammatory response.
      Endometriosis is characterized by the presence of endometrial cells with capacity
      to avoid apoptosis outside the uterus. Apoptosis plays a fundamental role for the
      pathogenesis of endometriosis. Eutopic endometrium from women with endometriosis
      has increased expression of anti-apoptotic factor and decreased expression of pro
      apoptotic factors compared with endometrium from healthy women. These differences
      could contribute to the survival of regurgitating endometrial cells into the
      peritoneal cavity and development of endometriosis. Increased apoptosis of Fas
      bearing immune cells in the peritoneal cavity may leads to their decreased
      scavenger activity that eventually results in prolonged survival of ectopic
      endometrial cells in women with endometriosis. This study is a current review of
      the literatures focused on the physiological role of apoptosis in normal
      endometrium and alterations in regulation of apoptosis in eutopic and ectopic
      endometrium from women with endometriosis. The role of apoptosis in the treatment
      of endometriosis is also reviewed.

PMID- 21196343
TI  - Recent advances in nano-based electrochemical biosensors: application in
      diagnosis and monitoring of diseases.
AB  - Based on biological molecules combined with nanostructured components, the news
      generations of electrochemical biosensors can employ different transducers
      (potentiometric, amperometric and impedimetric) converting the chemical
      information into a measurable amperometric signal. Following this contemporary
      theme, our main focus in this review is to discuss different methodologies for
      application in biosensing, whose signal transduction is based on electrochemical
      principles. We apply a discussion on recent trends involving different
      nanostructured materials, but without daring to contemplate all nanomaterials
      incessantly cited in literature, which leads us to believe that this moment is an
      unprecedented revolution in the preparation of electrochemical biodevices.
      Besides, some structures of bio-nano interface and different electrochemical
      biosensors involved in diagnosis systems are also discussed. We outline in
      several parts of the report how nanoscience technologies are emerging in
      diagnostic medicine, as well as convergence of electrochemistry and bio
      nanoscience. Our hopes for this review are that it can help different categories
      of researchers to understand the broad application area of electrochemistry and
      bioelectrochemistry, in order to detecting several types of diseases and
      biological phenomena.

PMID- 21196345
TI  - CD133 negative cancer stem cells in glioblastoma.
AB  - Glioblastomas (GBM) are paradigmatic for the investigation of cancer stem cells
      (CSC) in solid tumors. Recently, the discovery of CD133- CSC in addition to
      CD133+ CSC has substantially added to our understanding of the complexity of GBM
      CSC. This review gives an overview on our current knowledge on CD133- cells in
      GBM and describes five different hypothesizes on the nature of CD133- cells in
      GBM. In addition, we summarize the current knowledge on tumorigenic CD133- CSC,
      list available markers, describe the current controversies on the origin of CD133
      CSC, and discuss how the heterogeneity of CSC may correspond to the molecular
      heterogeneity of GBM.

PMID- 21196344
TI  - Endocrine disruptors, environmental oxygen, epigenetics and pregnancy.
AB  - The placenta and its myriad functions are central to successful reproductive
      outcomes. These functions can be influenced by the environment encountered
      throughout pregnancy, thereby altering the appropriate genetic programming needed
      to allow for sustained pregnancy and appropriate fetal development. This altered
      programming may result from epigenetic alterations related to environmental
      exposures. Epigenetic alterations are now being linked to several important
      reproductive outcomes, including early pregnancy loss, intrauterine growth
      restriction, congenital syndromes, preterm birth, and preeclampsia. The diversity
      of environmental exposures linked to adverse reproductive effects continues to
      grow. Much attention has focused on the role of endocrine disruptors in
      infertility, but recent work suggests that these chemicals may also have adverse
      effects in pregnancy and development. Environmental oxygen is also critical in
      pregnancy success. There are clear links between altered oxygen levels and
      placentation amongst other effects. As research continues to enhance our
      understanding of the molecular processes including epigenetic regulation that
      influence pregnancy, it will be critical to specifically examine how the
      environment, broadly defined, may play a role in altering these critical
      functions.

PMID- 21196346
TI  - Dentin: structure, composition and mineralization.
AB  - We review firstly the specificities of the different types of dentin present in
      mammalian teeth. The outer layers include the mantle dentin, the Tomes' granular
      and the hyaline Hopewell-Smith's layers. Circumpulpal dentin forming the bulk of
      the tooth, comprises intertubular and peritubular dentin. In addition to
      physiological primary and secondary dentin formation, reactionary dentin is
      produced in response to pathological events. Secondly, we evaluate the role of
      odontoblasts in dentin formation, their implication in the synthesis and
      secretion of type I collagen fibrils and non-collagenous molecules. Thirdly, we
      study the composition and functions of dentin extracellular matrix (ECM)
      molecules implicated in dentinogenesis. As structural proteins they are
      mineralization promoters or inhibitors. They are also signaling molecules. Three
      different forms of dentinogenesis are identified: i) matrix vesicles are
      implicated in early dentin formation, ii) collagen and some proteoglycans are
      involved in the formation of predentin, further transformed into intertubular
      dentin, iii) the distal secretion of some non-collagenous ECM molecules and some
      serum proteins contribute to the formation of peritubular dentin.

PMID- 21196347
TI  - Role of sulfur-containing gaseous substances in the cardiovascular system.
AB  - Gaseous mediators are important signaling molecules with properties that differ
      from other, larger signaling molecules. Small gaseous mediators readily cross
      cell membranes and can access sites on target molecules that would be
      inaccessible to bulkier molecules. They have a variety of signaling mechanisms,
      some well understood, some not. The family of gasotransmitters is growing, well
      known members include nitric oxide (NO) and carbon monoxide (CO). Newer
      candidates include the sulfur containing gases hydrogen sulfide (H2S), which has
      been shown to have a wide range of physiological functions, and more recently
      sulfur dioxide (SO2) has been studied as a potential new gasotransmitter. This
      review explores the production, regulation and role of the sulfur-containing
      gases H2S and SO2 at the level of the endothelial and vascular smooth muscle
      cells as well as the broader effects on the cardiovascular system under both
      physiological and pathophysiological conditions.

PMID- 21196348
TI  - Focal adhesion kinase signaling and function in pancreatic cancer.
AB  - In the United States and the European Union, pancreatic cancer is the fourth
      leading cause of cancer death in both men and women. Chemotherapy and radiation
      therapy have had little impact on survival, prompting the National Cancer
      Institute to declare that survival for pancreatic cancer has remained unchanged
      for three decades and its treatment has consistently been identified as an area
      of unmet medical need. Clearly, additional agents are needed to improve outcomes
      in this aggressive disease. Clinicians must translate the available knowledge of
      the molecular basis of this disease into rationale and effective therapeutic
      strategies for treatment. Pancreatic cancer has been found to have several
      genetic alterations and is, in fact, one of the tumors with the highest number of
      genetic mutations of any solid malignancy. These mutations include activation of
      K-ras and inactivation of p53, p16, and DPC4. Other alterations include
      upregulation of angiogenic factors and matrix metalloproteinases, dysregulation
      of growth factor receptors, and cytoplasmic kinases including focal adhesion
      kinase (FAK) and Src. The role of FAK in the pathogenesis of pancreatic cancer is
      discussed below and efforts aimed at the development of inhibitors of FAK for
      this disease are reviewed.

PMID- 21196349
TI  - Mold exposure and respiratory health in damp indoor environments.
AB  - Almost all modern buildings experience at least minor, and sometimes serious,
      water damage during their life span. Excess moisture in buildings becomes a
      critical factor for mold (fungal) proliferation in nutrient-rich environments. As
      a result, building occupants may be exposed to increased levels of microbial
      agents such as fungal spores, cell fragments, cell wall components, or toxins.
      Such exposures may result in various diseases and symptoms, both respiratory and
      non-respiratory. Respiratory health complaints are common in damp buildings and
      have been more thoroughly studied than non-respiratory complaints. Respiratory
      diseases and symptoms which may be produced by exposure to indoor fungi include
      asthma development, exacerbation of asthma, hypersensitivity pneumonitis, cough,
      wheeze, dyspnea (shortness of breath), nasal and throat symptoms, and respiratory
      infections. In addition to these illnesses, rhinosinusitis and sarcoidosis in
      water-damaged building occupants are also drawing more scientific attention. In
      this article, we explore the evidence for adverse effects of fungal exposure on
      respiratory health in damp indoor environments and potential disease mechanisms
      related to the exposure.

PMID- 21196350
TI  - Airborne algae and cyanobacteria: occurrence and related health effects.
AB  - Published information on airborne algae and cyanobacteria worldwide and the
      related human health effects is scarce. Since 1844, a total of 353 morphological
      taxa (genera or species) have been identified in aerobiological studies. However,
      due to diverse methodologies and different microorganisms targeted in these
      studies, direct comparisons on the occurrences of airborne algae and
      cyanobacteria in various studies are rather dubious. Thirty-eight airborne algae
      and cyanobacteria were shown to induce allergy, skin irritation, hay fever,
      rhinitis, sclerosis and respiratory problems when aerosolized and inhaled.
      Another 14 airborne taxa are known toxin producers posing threat to human health.
      Most frequently associated with health effects are the genera Chlorella,
      Scenedesmus, Chlorococcum, Klebsormidium (Hormidium) and Lyngbya. In the air of
      the Mediterranean city of Thessaloniki, we found 63 algal and cyanobacterial
      taxa, with 21 reported for the first time in the air. Seven taxa were potentially
      harmful. Algae and cyanobacteria can contribute significantly in the total air
      particle load, rendering them as causative agents for health issues when inhaled.

PMID- 21196352
TI  - Management of type-2 diabetes with anti-platelet therapies: special reference to
      aspirin.
AB  - Adult onset diabetes currently affects 380 million individuals worldwide and is
      expected to affect 380 million by 2025. Major defects contributing to this
      complex disease are insulin resistance and beta cell dysfunction. More than 80%
      of patients professing to type-2 diabetes are insulin resistant. Recent studies
      have shown that the Indian subcontinent ranks very high in the occurrence of
      Diabetes and Coronary artery disease (1, 2, 3). Patients with Type 2 diabetes
      carry an equivalent cardiovascular risk to that of a non-diabetic individual who
      has already experienced a coronary event. The risk of coronary artery disease in
      any given population seems to be 2-3 times higher in diabetics than non
      diabetics. Inflammation, platelet activation, endothelial dysfunction and
      coagulation are the four processes, whose interplay determines the development of
      cardiovascular disease. In this article, we provide a brief overview on platelet
      physiology, vascular dysfunction, platelet hyper-function, and the role of
      platelet related clinical complications in diabetes mellitus and what is know
      about the management of this complex disease with anti-platelet drugs such as
      aspirin and Clopidogrel.

PMID- 21196351
TI  - Dental pulp and dentin tissue engineering and regeneration: advancement and
      challenge.
AB  - Hard tissue is difficult to repair especially dental structures. Tooth enamel is
      incapable of self-repairing whereas dentin and cementum can regenerate with
      limited capacity. Enamel and dentin are commonly under the attack by caries.
      Extensive forms of caries destroy enamel and dentin and can lead to dental pulp
      infection. Entire pulp amputation followed by the pulp space disinfection and
      filling with an artificial rubber-like material is employed to treat the
      infection -- commonly known as root canal or endodontic therapy. Regeneration of
      dentin relies on having vital pulps; however, regeneration of pulp tissue has
      been difficult as the tissue is encased in dentin without collateral blood supply
      except from the root apical end. With the advent of modern tissue engineering
      concept and the discovery of dental stem cells, regeneration of pulp and dentin
      has been tested. This article will review the recent endeavor on pulp and dentin
      tissue engineering and regeneration. The prospective outcomes of current
      advancements and challenges in this line of research are discussed.

PMID- 21196353
TI  - Targeting EGFR in bilio-pancreatic and liver carcinoma.
AB  - The key role of epidermal growth factor receptor(EGFR) in tumorigenesis has been
      demonstrated in several cancer types, so recent clinical trials have investigated
      their activity/efficacy in different settings. Two different types of EGFR
      targeted agents were developed: monoclonal antibodies such as cetuximab and
      panitumumab, and tyrosine kinase inhibitors, such as gefitinib and erlotinib. In
      this review, we summarize the preclinical rational of potential activity and the
      most important clinical trials evaluated anti-EGFR targeted agents in non
      colorectal digestive cancer, both in monotherapy and in combination with other
      chemotherapeutic or targeted agents. Patient selection by use of biologic markers
      will identify which patients are more likely to respond, contributing to the
      successful use of these agents.

PMID- 21196356
TI  - Lipid peroxidation of membrane phospholipids in the vertebrate retina.
AB  - Retina is very rich in membranes containing polyunsaturated fatty acids. Reactive
      oxygen species initiates chain reactions of lipid peroxidation which injure the
      retina, especially the membranes that play important roles in visual function.
      Furthermore, biomolecules such as proteins or amino lipids can be covalently
      modified by lipid decomposition products. In retinal membranes, peroxidation of
      lipids is also usually accompanied by oxidation of membrane proteins. In
      consequence, lipid peroxidation may alter the arrangement of proteins in bilayers
      and by that interfere with their physiological role on the membrane function.
      Here, we review several studies on the lipid peroxidation of membrane
      phospholipids in retina. Particular emphasis is placed on the molecular changes
      of very long chain polyunsaturated fatty acids associated with protein
      modifications during peroxidation of photoreceptor membranes. Furthermore we use
      liposomes to analyze peroxidation of retinal lipids. Conjugated dienes formed
      from oxidized PUFAs, and TBARS products derived from the breakdown of these fatty
      acids located in phospholipids can be analyzed during lipid peroxidation of
      liposomes made of retinal lipids using Fe2+ and Fe3+ as initiators.

PMID- 21196355
TI  - Acrylamide in health and disease.
AB  - Acrylamide has been classified as a probable carcinogen and can be ingested,
      inhaled (e.g. tobacco smoke), or absorbed. Fried, starchy foods are the most
      prominent sources of exposure. The reaction between asparagine and fructose
      typically produces the most acrylamide in foods from plant sources. Preparation
      methods shown to affect acrylamide production include temperature and cooking
      oil. Hemoglobin adducts present a reliable short term measurement of acrylamide
      exposure; a variety of methods, predominately LC/MS-MS, have been used for
      acrylamide detection. Health effects of acrylamide include neurotoxicity and
      genotoxicity. It is believed that the electrophilic nature of acrylamide will
      allow it to adduct to thiol groups on nerve axons and proteins that regulate
      neurotransmitter exocytosis. Presynaptic nitric oxide (NO) may also play a role
      here. Reproductively, males demonstrate a decrease in sperm count, motility and
      morphology. Acrylamide produces clastogenic effects while glycidamide (GA), its
      metabolite, produces mutagenic effects. A number of protective measures against
      the effects of acrylamide are possible including probiotics, increased use of
      compounds known to decrease acrylamide production and bioengineering of precursor
      foods such as potatoes.

PMID- 21196357
TI  - Tissue engineering of bone: an ectopic rat model.
AB  - Tissue engineering is attempting to recreate the complexity of living tissues. In
      order to test a variety of scaffolds or cells that are constantly being
      developed, we describe here a model where tissue engineering of bone in a non
      osseous environment at subcutaneous thoracic site of DA rats generates. In this
      model, cell - matix interactions can mimic the normal cascade of bone development
      into a well organized ossicle like structure including newly formed bone marrow,
      during 3-4 weeks. Histogenesis of cartilage, bone and bone marrow is closely
      related to changes in molecular expression of essential early transcriptional
      regulators of osteoblast differentiation. We tested different organic, anorganic
      and polymeric scaffolds and their interaction with mesenchymal stem cells present
      in fresh bone marrow. In another series of experiments we tested mesenchymal
      populations separated from cultures of calvaria and periosteum for their ability
      to form bone in the same rat model. It is concluded that this in vivo model is
      very potent in studying cell-scaffold interactions affecting the temporal and
      spatial tissue engineering of bone.

PMID- 21196354
TI  - Myelin, copper, and the cuprizone model of schizophrenia.
AB  - In recent years increasing evidence is pointing toward white matter abnormalities
      in schizophrenia and other psychiatric disorders. The present paper will provide
      an overview over the role of myelin in cognition and brain function, and its
      potential involvement in brain disorders. Furthermore, we will examine one
      particular experimental model for the study of dysmyelination, created by the
      administration of the toxin cuprizone. Cuprizone, a copper chelator, causes white
      matter abnormalities in rodents. The administration of cuprizone during specific
      developmental periods allows for the targeting of specific brain areas for
      dysmyelination. Thus, cuprizone can be used to study the pathogenesis and
      pathophysiology of myelin deficiencies in the central nervous system, and its
      effect on behaviors relevant to psychiatric disorders.

PMID- 21196360
TI  - Protein kinase B/Akt regulation in diabetic kidney disease.
AB  - Many reviews have been written on protein kinase B/Akt focusing on its history
      dating back from the isolation of the Akt8 transforming murine leukemia virus by
      Staal in 1977, to the co-discovery of the Akt1 gene by the three groups in 1991
      (reviewed in 7). There are currently over 22,000 publications in the PubMed
      database with "Akt" as a keyword - these publications describe a wealth of
      diverse data on the physiological functions of Akt isoforms. Many of these
      publications describe roles of Akt ranging from its requirement for cellular
      processes such as glucose uptake, cell survival and angiogenesis to roles in
      diseases such as cancer and ischaemia (22). This review will focus on the
      evidence for Akt signaling in different kidney cells during diabetes, or diabetic
      nephropathy (DN).

PMID- 21196358
TI  - Adipose tissue as a stem cell source for musculoskeletal regeneration.
AB  - Adipose tissue is an abundant, easily accessible, and reproducible cell source
      for musculo-skeletal regenerative medicine applications. Initial derivation steps
      yield a heterogeneous population of cells of stromal vascular fraction (SVF)
      cells. Subsequent adherent selection of the SVF results in a relatively
      homogeneous population of adipose-derived stromal/stem cells (ASCs) capable of
      adipogenic, chondrogenic, myogenic, and osteogenic differentiation in vitro on
      scaffolds in bioreactors and in vivo in pre-clinical animal models. Unlike
      hematopoietic cells, ASCs do not elicit a robust lymphocyte reaction and instead
      release immunosuppressive factors, such as prostaglandin E2. These
      immunomodulatory features suggest that allogeneic and autologous ASCs will
      engraft successfully for tissue regeneration purposes. The differentiation and
      expansion potential of ASCs can be modified by growth factors, bio-inductive
      scaffolds, and bioreactors providing environmental control and biophysical
      stimulation. Gene therapy approaches using lentiviral transduction can be used to
      direct differentiation of ASCs to particular lineages. We discuss the utility of
      ASCs for musculo-skeletal tissue repair and some of the technologies that can be
      implemented to unlock the full regenerative potential of these highly valuable
      cells.

PMID- 21196361
TI  - The pathology of pituitary adenomas from a clinical perspective.
AB  - Pituitary adenomas present with a variety of clinical endocrine manifestations
      and arise in a sporadic setting or rarely as part of hereditary genetic
      syndromes. Molecular analysis of familial pituitary adenomas has provided
      significant insight into pituitary tumorigenesis. Some specific genes have been
      identified that predispose to pituitary neoplasia, but these are rarely involved
      in the pathogenesis of sporadic tumors. The number of identified genes involved
      in pituitary tumorigenesis is progressively increasing. The possible resulting
      mechanisms of action involve abnormalities in signal transduction pathways, cell
      cycle regulators, growth factors, chromosome stability and others. Further
      studies are needed to evaluate the clinical significance of genetic alterations
      and their implications for patient prognosis, as well as to identify targets for
      existing and new therapeutic options. The aim of this review is to focus on the
      molecular pathology of pituitary adenomas from a practical perspective and
      discuss the possible clinical implications which may relate to particular
      molecular alterations. We have summarised familial syndromes related to pituitary
      adenomas and considered the prognostic value of selected molecular alterations in
      these tumors.

PMID- 21196359
TI  - Therapeutic advances in women's cancers.
AB  - Cytotoxic therapy and surgery have improved outcomes for patients with
      gynecologic malignancies over the last twenty years, but women's cancers still
      account for over ten percent of cancer related deaths annually. Insights into the
      pathogenesis of cancer have led to the development of drugs that target molecular
      pathways essential to tumor survival including angiogenesis, DNA repair, and
      apoptosis. This review outlines several of the promising new biologically
      targeted drugs currently being tested to treat gynecologic malignancies.

PMID- 21196362
TI  - Injury responses and repair mechanisms of the injured growth plate.
AB  - The growth plate is responsible for longitudinal growth of children's long bones.
      However, being a cartilaginous tissue, the growth plate has a limited ability for
      regeneration and thus injured growth plate is often repaired by bony tissue
      resulting in bone growth defects of the involved limb. Understanding the
      pathophysiology of growth plate bony repair and developing preventative
      treatments remain a challenge. This review discusses previous and recent studies
      investigating growth plate injury responses and repair mechanisms in a rat tibial
      growth plate injury model. Following an injury, inflammatory, fibrogenic,
      osteogenic and bone-bridge maturation repair phases have been observed on days 1
      3, 3-7, 7-14 and 10 onwards, respectively. Important roles of several growth
      factors and cytokines (such as PDGF-BB, FGF-2, TNF-alpha? and IL-1beta) have been
      highlighted, regulating different phases of growth plate injury repair. Studies
      have also shown that while intramembranous ossification is the major mechanism
      responsible for the bony repair, endochondral ossification, to a lesser extent,
      also plays a role. Further understanding of the growth plate injury responses and
      bony repair mechanisms is still required.

PMID- 21196363
TI  - Transcriptional regulation of bone formation.
AB  - Bone formation in vertebrates depends on the proliferation and differentiation of
      chondrocytes and osteoblasts, which are derived from a mesenchymal precursor
      cells and are required for skeletal development. This process relies on many
      transcription factor genes that have functions in bone cell proliferation and
      differentiation. Over the years, various transcription factors that play
      essential roles for skeletal formation have been identified in in vivo and/or in
      vitro molecular and genetic studies. In regulation of bone formation, signaling
      pathways with these factors have also been established. Major transcription
      factors including Sox9, Runx2, and Osterix, which are active in chondrocytes or
      osteoblasts or even in both cells, are indispensable for chondrocyte and/or
      osteoblast differentiation. Here, the transcriptional regulation of these genes
      for bone formation will be reviewed on the basis of in vivo mouse models.

PMID- 21196364
TI  - Vulvar cancer as a target for molecular medicine.
AB  - Vulvar carcinoma is a rare female genital neoplasm. Although numerous molecular
      defects in vulvar carcinomas have been reported until now, no molecular markers
      that could be applied in daily clinical work have been identified so far.
      However, there is emerging evidence that specific mutations and gene expression
      patterns may be used as diagnostic tools in oncology. In this article we
      systematically review genetic alterations that may contribute to the development
      and progression of vulvar carcinoma. We conclude by suggesting molecular markers
      of potential clinical value in the diagnostics of this type of cancer.

PMID- 21196366
TI  - Diagnosis and monitoring of chronic viral hepatitis: serologic and molecular
      markers.
AB  - Chronic Hepatitis B (HBV) and Hepatitis C (HCV) virus infections are global
      health problems which may cause cirrhosis and even hepatocellular carcinoma.
      Hepatitis D virus (HDV) though a satellite virus of HBV, can also cause chronic
      infection. Serologic and molecular tools are needed for the diagnosis, monitoring
      and therapeutic management of chronic viral hepatitis associated with HBV, HDV
      and HCV. In HBV infection several serological markers are available for diagnosis
      and staging; while molecular assays are important for pretreatment evaluation,
      assessing drug response and identification of mutants. The endpoint of chronic
      HCV and HDV treatment is the sustained virological response, defined by an
      undetectable HCV/HDV RNA in serum with a sensitive assay 6 months after
      completion of treatment. HCV genotype and quantitative HCV RNA testing plays an
      important role in determining treatment duration, doses and also assess the
      likelihood of treatment response. Thus, virological assays are important in the
      diagnosis and management of individuals infected with chronic viral hepatitis.

PMID- 21196365
TI  - Endothelins in regulating ovarian and oviductal function.
AB  - In the last 30 years, remarkable progress has been made in our understanding of
      the biological role of endothelins in the regulation of reproductive function and
      fertility. A peptide hormone identified for its ability to regulate blood
      pressure has now been shown as a potent mediator of several reproductive
      pathways. Ligand- and receptor-specific roles have been identified and/or
      postulated during follicular development and ovulation as well as in the function
      and regression of the corpus luteum. In this review we have attempted to organize
      endothelin-mediated ovarian processes in a process-specific manner, rather than
      compile a review of ligand- or isoform-specific actions. Further, we have
      included a discussion on "post-ovarian" or oviductal function, as well as the
      future directions that we believe will increase our understanding of endothelin
      biology as a whole.

PMID- 21196368
TI  - Neurogenesis, NSCs, pathogenesis and therapies for Alzheimer's disease.
AB  - Neurogenesis occurs in the adult brain and neural stem cells (NSCs) reside in the
      adult central nervous system (CNS) of mammals. Adult NSCs offer tremendous
      potential for cellular therapy for the treatment of neurological diseases and
      injuries, particularly of Alzheimer's disease (AD). The contribution of newly
      generated neuronal cells of the adult brain to the functioning of the nervous
      system remains to be elucidated. Neurogenesis is enhanced in the brain of
      patients with AD. Enhanced neurogenesis would contribute to regenerative attempts
      in AD, to compensate for the neuronal loss. Adult neurogenesis holds the
      potential to generate aneuploid cells, a landmark of AD pathology. Aneuploid
      newly generated neuronal cells in the adult brain would contribute to the
      pathogenesis of AD. Adult neurogenesis would not only be beneficial, but also
      detrimental for patients with AD. We will review and discuss the potential of
      adult NSCs for the treatment of AD and their contribution to the pathogenesis of
      the disease, as well as the development of novel drugs and therapies for treating
      AD.

PMID- 21196369
TI  - Phytotherapy as alternative to hormone replacement therapy.
AB  - Phytoestrogens are a group of non-steroidal compounds of plant origin that
      present structural and functional similarities with estradiol. Isoflavones are
      their most widely known category. There are different mechanisms of action of
      isoflavones accepted, although they may be considered as selective modulators of
      estrogen receptors. On the other hand, Cimicifuga Racemosa is a perennial plant
      used traditionally for problems related to menstruation. Its action mechanisms
      have not been totally identified. There is a growing interest in the usefulness
      of phytotherapy in the treatment of symptoms and menopause-related diseases.
      Isoflavones and Cimicifuga Racemosa moderately improve vasomotor symptoms in
      menopausal women, particularly in those who have a greater number of hot flushes.
      Furthermore, trials performed with soy isoflavones have observed a reduction of
      the loss of bone mineral density in postmenopausal women and a slight decrease in
      LDL cholesterol. In short, phytotherapy will constitute a therapeutic option that
      can offer assistance to women who want to improve their quality of life through
      relief of vasomotor symptoms or benefit from other effects for their health.

PMID- 21196367
TI  - Effects of lifestyle interventions on inflammatory markers in the metabolic
      syndrome.
AB  - Metabolic syndrome (MetS) is a clustering of cardiovascular risk factors which
      places individuals at increased risk for cardiovascular morbidity and mortality.
      In addition to obesity and insulin resistance, inflammation is emerging as a
      potential etiologic factor of the syndrome. One hypothesis suggests that obesity
      contributes to insulin resistance through increased production of adipose-derived
      inflammatory cytokines. Currently, lifestyle change is the first line of
      treatment for MetS. Only recently, however, have studies begun exploring the
      effect of lifestyle interventions on the mediation of inflammation in individuals
      with MetS. This review summarizes the strongest evidence (i.e. randomized
      controlled trial data) for a role of lifestyle interventions (diet and/or
      exercise) on the improvement of inflammatory biomarkers in people with MetS. Of
      six studies assessed, lifestyle interventions were consistently successful at
      improving the inflammatory and metabolic profiles. Interestingly, improvements in
      the inflammatory profile were found to be largely independent of obesity. Data
      currently suggest that alterations in dietary composition may be the most
      effective lifestyle change, although there is a need for more research in this
      area.

PMID- 21196371
TI  - Angiogenic and lymphangiogenic cascades in the tumor microenvironment.
AB  - Blood and lymphatic vessels in tumor tissue are major components of the tumor
      microenvironment. These vessels are newly formed from pre-existing host vessels
      stimulated by pro-blood-angiogenic and pro-lymph-angiogenic (pro-blood/lymph
      angiogenic) factors expressed in tumor cells. Tumor cells establish a specific
      stromal microenvironment fostering tumor growth, in which blood/lymph
      angiogenesis are involved. The tumor-associated blood/lymph-angiogenesis is
      continually induced by complicated cytokine networks, namely pro-blood/lymph
      angiogenic factor-mediated paracrine and autocrine interactions among tumor cells
      and stromal cells including endothelial cells (ECs) and non-endothelial
      mesenchymal cells (neMCs). In this review, we provide an overview of the features
      of tumor-associated blood/lymph-angiogenesis based on recent and updated
      information obtained mainly from our studies. With regard to the constituent cell
      dependent molecular mechanisms that regulate tumor blood/lymph-angiogenesis, we
      focus on: 1) the role of blood/lymph-angiogenesis-related factors/receptors
      expressed in tumor cells; and 2) the role of blood/lymph-angiogenesis-related
      factors/receptors expressed in stromal cells (ECs and neMCs). Finally, we discuss
      the features of tumor-associated blood/lymph-anigogenesis, especially a vessel
      abnormality through the viewpoint of blood/lymph-angiogenic cascades in tumor
      microenvironment for better understanding of the tumor vascular biology.

PMID- 21196370
TI  - Calcium fructoborate: plant-based dietary boron as potential medicine for cancer
      therapy.
AB  - It was predicted that more B-containing molecules will be discovered that will
      prove useful in applications involving cell surface signaling, but insufficient
      progress was made in this general direction. The main objective of this review is
      to reveal other promising research directions for B-chemoprevention and
      chemotherapy using Calcium Fructoborate (CF). Targets include breast cancer,
      prostate cancer, lung cancer and cervical cancer. CF has been identified as Ca (
      (C6H10O6)2B)2o4H2O and is a natural product from plants (can be produced by
      chemical synthesis as well), and is efficient in the prevention and treatments
      (as adjuvant) of osteoporosis and osteoarthritis. CF showed inhibitory effects on
      MDA-MB-231 breast cancer cells as well, and enters the cell (most likely) by a co
      transport mechanism via a sugar transporter. Inside cells CF acts as an
      antioxidant and induces the overexpression of apoptosis-related proteins and
      eventually apoptosis.

PMID- 21196372
TI  - Periacinar retraction artifact of the prostate.
AB  - Retraction artifacts are well known phenomenon in diagnostic surgical pathology
      for a long time but they were usually considered as artificially produced tissue
      alteration. Some recent studies of retraction artifact in different tumors have
      focused on its diagnostic and/or prognostic role. Their presence in prostatic
      carcinoma may be used in diagnostic and prognostic purposes. Peritumoral
      retraction artefacts in prostatic carcinoma are more pronounced and more common
      around neoplastic glands compared to benign glands, gland with prostatic
      intraepithelial neoplasia and postatrophic hyperplasia that is the one of the
      most common mimickers of prostatic carcinoma. In addition, the presence of
      extensive retraction artifact in prostatic carcinomas is clearly associated with
      tumor features that indicate a more aggressive tumor phenotype and with shorter
      biochemical recurrence-free survival. Studies at the molecular level demonstrate
      that retraction artifact may be attributed to molecules produced by reactive
      cancer stroma. The origin of retraction artifact in tumor specimens is unknown
      but they are probably the consequence of lack of basal cells and /or stromal
      changes but not simply artifacts due to laboratory procedures.

PMID- 21196374
TI  - Inflammation and oxidative damage in Alzheimer's disease: friend or foe?
AB  - The two major neuropathologic hallmarks of AD are extracellular Amyloid beta
      plaques and intracellular neurofibrillary tangles. A number of additional
      pathogenic mechanisms have been described, including inflammation and oxidative
      damage. Regarding inflammation, several cytokines and chemokines have been
      detected both immunohistochemically and in Cerebrospinal Fluid from patients.
      Some of them, including Tumor Necrosis Factor-alpha, Interferon-gamma-inducible
      Protein-10, Monocyte Chemotactic Protein-1 and Interleukin-8, are increased in AD
      and in Mild Cognitive Impairment, considered the prodromal stage of AD,
      suggesting that these modifications occur very early during the development of
      the disease, possibly explaining the failure of trials with anti-inflammatory
      agents in patients with severe AD. Further evidence suggests that cytokines and
      chemokines could play a role in other neurodegenerative disorders. These
      disorders are considered multifactorial diseases, and genetic factors influence
      pathological events and contribute to change the disease phenotype from patient
      to patient. Gene polymorphisms in crucial molecules, including cytokines,
      chemokines and molecules related to oxidative stress, may act as susceptibility
      factors, or may operate as regulatory factors, modulating the severity of
      pathogenic processes.

PMID- 21196376
TI  - WNT signaling and the regulation of ovarian steroidogenesis.
AB  - One of the major functions of the ovary is the biosynthesis of steroid hormones,
      which are essential for the development of secondary sexual characteristics at
      puberty, for subsequent ovarian function, and for the establishment and
      maintenance of pregnancy. Increases in our understanding of the molecular
      mechanisms governing the control of ovarian steroidogenesis have greatly improved
      our understanding of the female reproductive cycle, as well as the pathogenesis
      of reproductive disorders such as polycystic ovarian syndrome and premature
      ovarian failure. The pituitary gonadotropins follicle stimulating hormone (FSH)
      and luteinizing hormone (LH) are the main endocrine regulators of ovarian
      steroidogenesis, and act by directly or indirectly modulating the activity of a
      multitude of intracellular signaling pathways. The WNT/CTNNB1 pathway, which is
      now believed to be a significant contributor to the regulation of ovarian
      steroidogenesis, could be one of the pathways modulated by gonadotropin
      signaling. This review will focus on the emerging role of WNT/CTNNB1 signaling in
      the regulation of steroidogenesis, with emphasis on potential mechanisms of
      interaction with FSH/LH signaling in ovarian granulosa and luteal cells.

PMID- 21196373
TI  - Natural killer T cells in health and disease.
AB  - Natural killer T (NKT) cells are a subset of T lymphocytes that share surface
      markers and functional characteristics with both conventional T lymphocytes and
      natural killer cells. Most NKT cells express a semi-invariant T cell receptor
      that reacts with glycolipid antigens presented by the major histocompatibility
      complex class I-related protein CD1d on the surface of antigen-presenting cells.
      NKT cells become activated during a variety of infections and inflammatory
      conditions, rapidly producing large amounts of immunomodulatory cytokines. NKT
      cells can influence the activation state and functional properties of multiple
      other cell types in the immune system and, thus, modulate immune responses
      against infectious agents, autoantigens, tumors, tissue grafts and allergens. One
      attractive aspect of NKT cells is that their immunomodulatory activities can be
      readily harnessed with cognate glycolipid antigens, such as the marine sponge
      derived glycosphingolipid alpha-galactosylceramide. These properties of NKT cells
      are being exploited for therapeutic intervention to prevent or treat cancer,
      infections, and autoimmune and inflammatory diseases.

PMID- 21196375
TI  - Kisspeptins and the neuroendocrine control of reproduction.
AB  - Reproductive function, as essential for the survival of species, is under the
      control of a vast array of regulatory factors that ultimately modulate the
      release of GnRH. However, GnRH neurons lack the ability to directly sense most of
      these signals; hence, intermediate pathways are required. Kisspeptins have
      recently emerged as a pivotal piece in the reproductive brain, serving primarily
      as conduits for central and peripheral regulatory cues of GnRH release. Different
      populations of hypothalamic Kiss1 neurons have been described, which mediate
      either the positive or negative feedback of sex steroids in the sexually
      differentiated brain of rodents. Kisspeptins, however, are not the only recently
      appointed contributors to this integrative process. Indeed, neurokinin B (NKB)
      and dynorphin have been described to co-localize within Kiss1 neurons at the
      arcuate nucleus in different species, and may contribute to the regulation of
      kisspeptin release. In this work, we provide a concise overview of the major
      reproductive headlines of kisspeptins, focusing on their role as mediators of sex
      steroid feedback and their interaction with key neurotransmitters, such as NKB
      and dynorphin.

PMID- 21196377
TI  - Tryptophan metabolism in animals: important roles in nutrition and health.
AB  - L-Tryptophan is a nutritionally essential amino acid for monogastric animals and
      preweaning ruminants because it cannot be synthesized in the body. Besides
      serving as a building block for proteins, tryptophan is a critical nutrient for
      the functions of nervous and immune systems. Over the past decades, much
      attention has been directed to study the role of tryptophan as a limiting amino
      acid in mammalian and avian nutrition. However, emerging evidence from recent
      studies shows that tryptophan and its metabolites (e.g., serotonin (5
      hydroxytryptamine, 5-HT) and melatonin)) can regulate feed intake, reproduction,
      immunity, neurological function, and anti-stress responses. Additionally,
      tryptophan may modulate gene expression and nutrient metabolism to impact whole
      body homeostasis in organisms. Thus, adequate intake of this amino acid from the
      diet is crucial for growth, development, and health of animals and humans.

PMID- 21196379
TI  - MR spectroscopy in heart failure.
AB  - Magnetic resonance spectroscopy (MRS) is an established technique for the non
      invasive assessment of myocardial metabolism. MRS is ideal for the evaluation of
      heart failure, as it allows quantification of the primary energy source for all
      myocardial cellular functions (ATP), the energy reserve phosphocreatine (PCr),
      and the creatine kinase reaction, which maintains cellular energy equilibrium.
      PCr forms the primary ATP buffer in the cell via the creatine kinase (CK)
      reaction and is involved in transporting the chemical energy from the ATP
      producing mitochondria to the ATP-consuming contractile proteins. Using
      31phosphorus (31P) MRS, a low cardiac PCr/ATP has consistently been found in
      patients with heart failure, supporting the hypothesis that the failing heart is
      energy starved. The use of 1H MRS has allowed the detection of total creatine,
      which when combined with 31P MRS, provides an in depth examination of the
      creatine kinase reaction. MRS signals from 31P, 1H, 23Na and 13C, including novel
      hyperpolarization techniques, have provided considerable insight into the
      understanding of energy metabolism in the healthy and diseased heart.

PMID- 21196380
TI  - Hsp60: molecular anatomy and role in colorectal cancer diagnosis and treatment.
AB  - Quantitative changes in Hsp60 during the development of some tumors suggest that
      this chaperonin plays a role in carcinogenesis. A description of the specific
      role(s) of Hsp60 in tumor-cell growth and proliferation is still incomplete, but
      it is already evident that monitoring its levels and distribution in tissues and
      fluids has potential for diagnosis and staging, and for assessing prognosis and
      response to treatment. Although Hsp60 is considered an intramitochondrial
      protein, it has been demonstrated in the cytosol, cell membrane, vesicles, cell
      surface, extracellular space, and blood. The knowledge that Hsp60 occurs at all
      these locations opens new avenues for basic and applied research. It is clear
      that elucidating the mechanisms by which the chaperonin arrives at these various
      locations, and characterizing its functions in each of them will provide
      information useful for understanding carcinogenesis and for developing diagnostic
      and therapeutic tools for clinical oncology. Some of these issues pertinent to
      colorectal cancer (CRC) are discussed in this article.

PMID- 21196378
TI  - Cognition, dopamine and bioactive lipids in schizophrenia.
AB  - Schizophrenia is a remarkably complex disorder with a multitude of behavioral and
      biological perturbations. Cognitive deficits are a core feature of this disorder,
      and involve abnormalities across multiple domains, including memory, attention,
      and perception. The complexity of this debilitating illness has led to a view
      that the key to unraveling its pathophysiology lies in deconstructing the
      clinically-defined syndrome into pathophysiologically distinct intermediate
      phenotypes. Accumulating evidence suggests that one of these intermediate
      phenotypes may involve phospholipid signaling abnormalities, particularly in
      relation to arachidonic acid (AA). Our data show relationships between levels of
      AA and performance on tests of cognition for schizophrenia patients, with defects
      in AA signaling associated with deficits in cognition. Moreover, dopamine may
      moderate these relationships between AA and cognition. Taken together, cognitive
      deficits, dopaminergic neurotransmission, and bioactive lipids have emerged as
      related features of schizophrenia. Existing treatment options for cognitive
      deficits in schizophrenia do not specifically target lipid-derived signaling
      pathways; understanding these processes could inform efforts to identify novel
      targets for treatment innovation.

PMID- 21196381
TI  - Physiological importance and control of non-shivering facultative thermogenesis.
AB  - This review examines general and evolutionary aspects of temperature homeostasis,
      focusing on mammalian facultative or adaptive thermogenesis and its control by
      the sympathetic nervous system and hormones. Thyroid hormone acquired a new role
      with the advent of homeothermy enhancing facultative thermogenesis by interacting
      synergistically with the sympathetic nervous system, and directly increasing
      basal metabolic rate (obligatory thermogenesis). Facultative thermogenesis is
      triggered by cold. The major site of facultative thermogenesis in mammals is
      brown adipose tissue, endowed with abundant mitochondria rich in a protein called
      uncoupling protein-1. This protein can uncouple phosphorylation in a controlled
      manner, releasing the energy of the proton-motive force as heat. Its synthesis
      and function are regulated synergistically by the sympathetic nervous system and
      thyroid hormone and modulated by other hormones directly, or indirectly,
      modulating sympathetic activity as well as thyroid hormone secretion and
      activation in brown adipose tissue. Alternate, evolutionary older forms of
      facultative thermogenesis activated in transgenic mice with disabled brown
      adipose tissue thermogenesis reveal this latter as the culmination of energy
      efficient facultative thermogenesis.

PMID- 21196382
TI  - Roles of phytochemicals in amino acid nutrition.
AB  - Chinese herbal medicine (CHM) is often used as dietary supplements to maintain
      good health in animals and humans. Here, we review the current knowledge about
      effects of CHM (including ultra-fine Chinese herbal powder, Acanthopanax
      senticosus extracts, Astragalus polysaccharide, and glycyrrhetinic acid) as
      dietary additives on physiological and biochemical parameters in pigs, chickens
      and rodents. Additionally, we propose possible mechanisms for the beneficial
      effects of CHM on the animals. These mechanisms include (a) increased digestion
      and absorption of dietary amino acids; (b) altered catabolism of amino acids in
      the small intestine and other tissues; (c) enhanced synthesis of functional amino
      acids (e.g., arginine, glutamine and proline) and polyamines; and (d) improved
      metabolic control of nutrient utilization through cell signaling. Notably, some
      phytochemicals and glucocorticoids share similarities in structure and
      physiological actions. New research findings provide a scientific and clinical
      basis for the use of CHM to improve well-being in livestock species and poultry,
      while enhancing the efficiency of protein accretion. Results obtained from animal
      studies also have important implications for human nutrition and health.

PMID- 21196383
TI  - Inverse-fluorescence correlation spectroscopy: more information and less
      labeling.
AB  - Inverse-Fluorescence Correlation Spectroscopy (iFCS) is a recently developed
      modification of standard FCS that allows analysis of particles and biomolecules
      without labeling. The particles generate no signal; instead the signal is
      generated by a surrounding medium. Particles diffusing through the FCS-detection
      volume displace a fraction of the surrounding medium, causing transient dips in
      the detected signal. These give information about the mobility and concentration
      of the analyzed particles. Also labeled particles can be analyzed, whereby their
      signal is cross-correlated with that from the surrounding medium (iFCCS). This
      can give information about the volume of the labeled particles, or alternatively
      about the size of the detection volume. Also the interaction of unlabeled
      particles with small, labeled ligands can be analyzed with iFCCS. This allows
      using cross-correlation as a sensitive indication of binding, even though only
      one binding-partner is labeled. This review describes the principles of iFCS and
      iFCCS and measurements of microspheres dissolved in a surrounding medium
      containing alexa 488. We also discuss practical considerations, and future
      possibilities for analyses of biomolecules.

PMID- 21196384
TI  - Emission of bacteria and fungi in the air from wastewater treatment plants - a
      review.
AB  - An increase in global population, coupled with intensive development of industry
      and agriculture, has resulted in the generation and accumulation of large amounts
      of waste around the world. The spread of pathogenic microorganisms, endotoxins,
      odours and dust particles in the air is an inevitable consequence of waste
      production and waste management. Thus, the risk of infections associated with
      wastewater treatment plants (WWTPs) has become of a particular importance in
      recent decades. Sewage and unstable sludge contain various pathogens such as
      viruses, bacteria, and human and animal parasites. These microorganisms can be
      transmitted to the ambient air in wastewater droplets, which are generated during
      aeration or mechanical moving of the sewage. Bioaerosols generated during
      wastewater treatment may therefore pose a potential health hazard to workers of
      these plants or to habitants of their surroundings. The degree of human exposure
      to airborne bacteria, fungi, endotoxin and other allergens may vary significantly
      depending upon the type and the capacity of a plant, kind of the facilities,
      performed activities and meteorological conditions.

PMID- 21196385
TI  - Haplotype complementarity under mutational pressure.
AB  - Natural populations do not correspond to Mendelian populations. Effective
      populations are much smaller, inbreeding higher, and organization of large number
      of genes into chromosomes connected with relatively low recombination rate
      invalidates the law of independent gene assortment. Under such conditions, a
      large number of genes is inherited as clusters and evolves as genetic units.
      Computer simulations have shown that mutations inside clusters are not eliminated
      independently by purifying selection but, instead, the whole clusters tend to
      complement each other. It means that whenever one haplotype carries one of two
      possible alleles, the other haplotype at that locus carries the other allele;
      thus inherited recessive deleterious diseases do not affect the health of the
      phenotype even if their fraction in the genome is high. This complementation
      seems to be a winning strategy in small or spatially distributed populations. We
      discuss possible consequences of this complementarity.

PMID- 21196386
TI  - Cold defence responses: the role of oxidative stress.
AB  - Low temperatures provoke increased production of heat accompanied by increased
      respiration, oxygen consumption and the production of partially reduced oxygen
      species called ROS. ROS induce different forms of cellular oxidative damage,
      disturb the redox state and can change the activity of several metabolic enzymes.
      Organisms have developed a functionally connected set of anti-oxidant enzymes and
      low molecular mass compounds (together termed the ADS) that metabolise primary
      ROS. If ROS production within cells overwhelms the ADS, oxidative damage arises
      and oxidative stress can occur. Short-term cold exposure in endotherms leads to
      oxidative stress. As cold exposure persists organisms develop adaptive changes
      toward reducing ROS production and increasing the ADS. In contrast, heterotherms
      and ectotherms as a normal part of their over-wintering strategy slow down
      metabolism, oxygen consumption and subsequently cause ROS production. Increased
      baseline activity of key anti-oxidant enzymes as well as 'secondary' enzymatic
      defence and/or glutathione levels in preparation for a putative oxidative
      stressful situation arising from tissue re-oxygenation seems to be the preferred
      evolutionary adaptation of such animals exposed to low environmental
      temperatures.

PMID- 21196388
TI  - Assessment of airborne microorganisms by real-time PCR: optimistic findings and
      research challenges.
AB  - Most airborne microorganisms are natural components of our ecosystem. Soil,
      vegetation and animals, including humans, are sources for aerial release of these
      living or dead cells. In the past, assessment of airborne microorganisms was
      mainly restricted to occupational health concerns. Indeed, in several
      occupations, exposure to very high concentrations of non-infectious airborne
      bacteria and fungi, result in allergenic, toxic or irritant reactions. Recently,
      the threat of bioterrorism and pandemics have highlighted the urgent need to
      increase knowledge of bioaerosol ecology. More fundamentally, airborne bacterial
      and fungal communities begin to draw much more consideration from environmental
      microbiologists, who have neglected this area for a long time. This increased
      interest of scientists is to a great part due to the development and use of real
      time PCR techniques to identify and quantify airborne microorganisms. Even if the
      advantages of the PCR technology are obvious, researchers are confronted with new
      problems. This review describes the methodological state of the art in
      bioaerosols field and emphasizes the future challenges and perspectives of the
      real-time PCR-based methods for airborne microorganism studies.

PMID- 21196389
TI  - Advances in EGFR-directed therapy in head and neck cancer.
AB  - Initial research showed that EGFR targeting through known single agents, both
      monoclonal antibodies and small-molecule tyrosine-kinase inhibitors, applied to
      patients with refractory head and neck cancer, resulted in low response rates and
      short median survival times. However, the combination of Cetuximab with
      radiotherapy in patients with locally advanced disease and with a combination of
      platinum and fluorouracil in the setting of relapsed and/or metastatic disease
      resulted in a sharp improvement compared to standard therapy. Cetuximab entered
      clinical practice in both indications. Other anti-EGFR drugs, although showing
      activity, have not demonstrated an improvement of the results of standard
      therapy. Unfortunately, no molecular parameter emerged as a useful tool in
      predicting activity, thus impairing clinical applications. Only skin rash was
      repeatedly shown to be related with drug activity. Although generally well
      tolerated, class and drug specific toxicities can be troublesome and require
      knowledge and expertise for an optimal management. Further research is needed in
      order to find the best ways of integrating the anti-EGFR strategy with current
      standards of care.

PMID- 21196390
TI  - Modulation of hematopoiesis through histamine receptor signaling.
AB  - Histamine is one of the most versatile biogenic amines targeting a variety of
      cells through extra- and intracellular binding sites and specific receptors,
      which trigger different signal transduction pathways. It has been associated with
      cell growth ever since G. Kahlson demonstrated that its synthesis was increased
      in rapidly growing tissues of plants and animals. He proposed that the newly
      formed amine, as opposed to its stored counterpart, might play a major role in
      growth processes. Later on, a number of investigators provided evidence for the
      contribution of histamine to the expansion of normal and malignant cells, whether
      of hematopoietic origin or not. These studies have generated conflicting results,
      revealing growth-promoting as well as inhibitory effects, most likely because the
      final outcome of exposure to histamine depends on the signaling pathways
      triggered by distinct receptors and their differential distribution among the
      target population. The purpose of the present review is to outline our current
      understanding of the regulatory functions of histamine during growth and
      differentiation of hematopoietic progenitors, focusing on those mediated through
      its H4 receptor.

PMID- 21196391
TI  - The endocrinology of perimenopause: need for a paradigm shift.
AB  - Perimenopause, rather than a time of declining estrogen, is characterized by
      three major hormonal changes that may begin in regularly menstruating women in
      their mid-thirties: erratically higher estradiol levels, decreased progesterone
      levels (in normally ovulatory, short luteal phase or anovulatory cycles), and
      disturbed ovarian-pituitary-hypothalamic feedback relationships. Recent data show
      that approximately a third of all perimenopausal cycles have a major surge in
      estradiol occurring de novo during the luteal phase. This phenomenon, named
      "luteal out of phase (LOOP)" event, may explain a large proportion of symptoms
      and signs for symptomatic perimenopausal women. Large urinary hormone data-sets
      from women studied yearly over a number of years in the Study of Women Across the
      Nation (SWAN) and in the Tremin data will eventually provide a more clear
      prospective understanding of within-woman hormonal changes. Predicting menopause
      proximity with FSH or Inhibin B levels is documented to be ineffective. Anti
      Mullerian hormone levels may prove predictive. Finally, there is an urgent need
      to change perimenopause understandings, language and therapies used for midlife
      women's symptoms to reflect these hormonal changes.

PMID- 21196392
TI  - The stem cell fitness landscape and pathways of molecular leukemogenesis.
AB  - The relative risk of clonal evolution to either myelodysplasia (MDS) or acute
      myelogenous leukemia (AML) is high in patients with chronic bone marrow failure.
      From 10 to 20% of acquired aplastic anemia survivors will develop clonal
      evolution within the decade following their diagnosis as will 40% of patients
      with some of the inherited bone marrow failure syndromes. Studies on bone marrow
      failure states have provided some perspective on molecular pathogenesis of marrow
      failure and have also provided insights on the adaptive nature of clonal
      evolution. We review the scientific evidence validating this model, emphasize the
      importance of the fitness landscape in the stem cell pool, outline the clinical
      and investigative implications of the model, suggest that the lack of fitness in
      the starting pool accounts for the phenomenon of oncogene addiction, promote the
      value of the model for the evaluation of prevention strategies, and argue that
      experiments focusing attention on the relative phenotypes of neoplastic stem cell
      clones and pools of unfit stem cells from which they evolved will provide a
      useful paradigm of carcinogenesis in general.

PMID- 21196393
TI  - EGFR pathway in advanced non-small cell lung cancer.
AB  - Chemotherapy is the standard of care for patients with advanced stage non-small
      cell lung cancer (NSCLC) because of the a modest improvement in survival and
      quality of life but its efficacy has already reached a plateau. Several molecular
      targets involved in the uncontrolled growth of lung cancer cells has been
      recently discovered and Epidermal Growth Factor Receptor (EGFR) pathway is as a
      key therapeutic target. Strategies to block such pathway include tyrosine kinase
      inhibitors (TKIs) and monoclonal antibodies. Erlotinib and gefitinib are two EGFR
      TKI active against NSCLC. Their efficacy has been proven to be definitively
      superior in presence of activating EGFR mutation in the tumor. This evidence does
      not apply to the monoclonal antibody cetuximab, which efficacy in NSCLC was
      recently demonstrated in a single phase III study. The good tolerability profile
      of EGFR inhibitors make these agents suitable for maintenance and adjuvant
      setting, while sequencing of EGFR-TKIs and chemotherapy seems to be preferred.
      This article reviews the role of EGFR inhibitors focusing mainly on compounds in
      phase III clinical development.

PMID- 21196387
TI  - Maternal amino acid supplementation for intrauterine growth restriction.
AB  - Maternal dietary protein supplementation to improve fetal growth has been
      considered as an option to prevent or treat intrauterine growth restriction.
      However, in contrast to balanced dietary supplementation, adverse perinatal
      outcomes in pregnant women who received high amounts of dietary protein
      supplementation have been observed. The responsible mechanisms for these adverse
      outcomes are unknown. This review will discuss relevant human and animal data to
      provide the background necessary for the development of explanatory hypotheses
      and ultimately for the development therapeutic interventions during pregnancy to
      improve fetal growth. Relevant aspects of fetal amino acid metabolism during
      normal pregnancy and those pregnancies affected by IUGR will be discussed. In
      addition, data from animal experiments which have attempted to determine
      mechanisms to explain the adverse responses identified in the human trials will
      be presented. Finally, we will suggest new avenues for investigation into how
      amino acid supplementation might be used safely to treat and/or prevent IUGR.

PMID- 21196396
TI  - Obesity and thyroid cancer.
AB  - With the current trend of alarming rise in obesity rates, the health impacts of
      excess weight will become more apparent. While an increased incidence of
      cardiovascular disease and diabetes mellitus has been well documented, the
      association between obesity and carcinogenesis is just being appreciated and is
      receiving increasing attention. The current review focuses on the evidence
      linking thyroid cancer with obesity. We conclude that there is sufficient
      evidence that obesity can predispose to an increased risk of thyroid cancer in
      both men and women. This population-based association is mainly explained at a
      biological level through specific obesity-related endocrinopathies.

PMID- 21196394
TI  - Boron-doped diamond nano/microelectrodes for biosensing and in vitro
      measurements.
AB  - Since the fabrication of the first diamond electrode in the mid 1980s, repid
      progress has been made on the development and application of this new type of
      electrode material. Boron-doped diamond (BDD) electrodes exhibit outstanding
      properties compared to oxygen-containing sp2 carbon electrodes. These properties
      make BDD electrodes an ideal choice for use in complex samples. In recent years,
      BDD microelectrodes have been applied to in vitro measurements of biological
      molecules in tissues and cells. This review will summarize recent progress in the
      development and applications of BDD electrodes in bio-sensing and in vitro
      measurements of biomolecules. In the first section, the methods for BDD diamond
      film deposition and BDD microelectrodes preparation are described. This is
      followed by a description and discussion of several approaches for
      characterization of the BDD electrode surface structure, morphology, and
      electrochemical activity. Further, application of BDD microelectrodes for use in
      the in vitro analysis of norepinephrine (NE), serotonin (5-HT), nitric oxide
      (NO), histamine, and adenosine from tissues are summarized and finally some of
      the remaining challenges are discussed.

PMID- 21196398
TI  - Obesity and prostate cancer: collateral damage in the battle of the bulge.
AB  - Prostate cancer is the most common non-cutaneous malignancy diagnosed in US men.
      With the increasing prevalence of obesity, it is of interest how this condition
      impacts prostate cancer. However, only recently has the relationship between
      obesity and prostate cancer been earnestly studied by investigators. Indeed, the
      relationship between obesity and prostate cancer appears to be complex one.
      Therefore, we sought to review the most recent and relevant epidemiological data
      discussing the link between prostate cancer and obesity. In this review, we will
      discuss both "biological" and "non-biological" means by which obesity may
      potentially impact prostate cancer.

PMID- 21196397
TI  - Epileptiform activity in the limbic system.
AB  - Mesial temporal lobe epilepsy (MTLE) is a common neurological disorder
      characterized by hyperexcitability of limbic structures. Studies in epileptic
      patients and animal models of MTLE indicate that epileptiform activity arise
      primarily from limbic areas (e.g. hippocampus) with secondary propagation to
      cortical areas. A wealth of evidence indicates that epileptiform activity is
      associated with complex patterns in the expression and function of ion channels,
      receptors and transporters. Accordingly, several studies portrait MTLE as a post
      transcriptional acquired channelopathy. The present review describes the most
      common features of epileptiform activity emerging from animal models of limbic
      epileptogenesis and critically discusses the supporting evidence that MTLE is a
      complex acquired channelopathy.

PMID- 21196399
TI  - Occupational exposure to microorganisms used as biocontrol agents in plant
      production.
AB  - Exposure to bioaerosols containing fungi and bacteria may cause various
      deleterious respiratory health effects. Fungi and bacteria are commercially
      produced and applied to the environment as microbiological pest control agents
      (MPCAs). Attention has been drawn towards the exposure and health risks due to
      the use of commercially important MPCAs. As part of a risk evaluation this paper
      intends to review whether the exposure to MPCAs (Beauveria bassiana, Verticillium
      lecanii, Trichoderma harzianum, T. viride, T. polysporum, Paecilomyces
      fumosoroseus, P. lilacinus, Streptomyces griseoviridis, Bacillus subtilis and Ba.
      thuringiensis) exceeds background exposure levels. The paper is further aimed to
      focus on the aerosolization of MPCAs in relation to exposure and human
      inhalation. From the few studies about exposures it is concluded that both people
      handling MPCAs in occupational settings and residents of an area where MPCAs have
      been applied may be exposed to MPCAs. The highest exposures to MPCAs are found
      for people applying MPCAs. In 2 of 12 environments exposure to applied MPCAs were
      higher than exposure to the total number of bacteria or fungi.

PMID- 21196395
TI  - Protective mechanisms by cystatin C in neurodegenerative diseases.
AB  - Neurodegeneration occurs in acute pathological conditions such as stroke,
      ischemia, and head trauma and in chronic disorders such as Alzheimer's disease,
      Parkinson's disease, and amyotrophic lateral sclerosis. While the cause of
      neuronal death is different and not always known in these varied conditions,
      hindrance of cell death would be beneficial in the prevention of, slowing of, or
      halting disease progression. Enhanced cystatin C (CysC) expression in these
      conditions caused a debate as to whether CysC up-regulation facilitates
      neurodegeneration or it is an endogenous neuroprotective attempt to prevent the
      progression of the pathology. However, recent in vitro and in vivo data have
      demonstrated that CysC plays protective roles via pathways that are dependent on
      inhibition of cysteine proteases, such as cathepsin B, or by induction of
      autophagy, induction of proliferation, and inhibition of amyloid-beta
      aggregation. Here we review the data demonstrating the protective roles of CysC
      under conditions of neuronal challenge and the protective pathways induced under
      various conditions. These data suggest that CysC is a therapeutic candidate that
      can potentially prevent brain damage and neurodegeneration.

PMID- 21196400
TI  - MTSS1: a multifunctional protein and its role in cancer invasion and metastasis.
AB  - MTSS1 (metastasis suppressor-1) was first identified as a metastasis suppressor
      missing in metastatic bladder carcinoma cell lines. The down-regulation of MTSS1
      that may be caused by DNA methylation was also observed in many other types of
      cancer. While accumlating evidence for the function of MTSS1 support the concept
      that it is unlikely to be a metastasis suppressor, but actually acts as a
      scaffold protein that interacts with multiple partners to regulate actin
      dynamics. It has also been demonstrated that MTSS1 is involved in the Shh
      signaling pathway in the developing hair follicle and in basal cell carcinomas of
      the skin. Such evidence indicates that MTSS1 as a multiple functional molecular
      player and has an important role in development, carcinogenesis and metastasis.
      However, the biochemical mechanisms by which MTSS1 functions in cells and the
      physiological role of this protein in animals remain largely unknown. In this
      review, we will discuss the current knowledge of MTSS1's role in cancer
      metastasis, carcinogenesis, and development. The clinical significance of MTSS1
      will also be discussed.

PMID- 21196402
TI  - Beta-2-receptor regulation of immunomodulatory proteins in airway smooth muscle.
AB  - Airway smooth muscle (ASM) cells have been shown to secrete significant amounts
      of immunomodulatory factors (IMFs), many of which are typically ascribed to
      trafficking leukocytes (e.g., GM-CSF, IL-6, IL-13, and eotaxin), and may be
      indicative of an immunomodulatory role for ASM in control of airway function, as
      well as in airway diseases states associated with acute and/or chronic
      inflammation, such as asthma and COPD. Furthermore, epinephrine analogues such as
      albuterol, which ligate the G-protein coupled beta-2-receptor and have been
      clinically applied to promote ASM relaxation and bronchodilation in the treatment
      of asthma and COPD, also have been reported to downregulate IMF release by ASM,
      both individually and in additive fashion, in combination with corticosteroids.
      Based on experimental data, an inverse agonist/agonist model is proposed to
      explain these behaviors modeled on cell stimulatory states and G-protein coupled
      receptor activation. The ramifications of the model are considered in light of
      unexplained paradoxical clinical findings, and may provide a model for the
      understanding of beta-2-receptor agonist modulation of airway inflammation and
      function.

PMID- 21196401
TI  - Sleep and innate immunity.
AB  - Many pro-inflammatory molecules, such as interleukin-1 beta (IL-1 beta) and tumor
      necrosis factor-alpha (TNF-alpha) are somnogenic, while many anti-inflammatory
      molecules inhibit sleep. Sleep loss increases the production/release of these
      sleep regulatory pro-inflammatory molecules. Further, sleep changes occurring
      during various pathologies are mediated by these inflammatory substances in
      response to pathogen recognition and subsequent inflammatory cellular pathways.
      This review summarizes information and concepts regarding inflammatory mechanisms
      of the innate immune system that mediate sleep. Further, we discuss sleep-immune
      interactions in regards to sleep in general, pathologies, and sleep as a local
      phenomenon including the central role that extracellular ATP plays in the
      initiation of sleep.

PMID- 21196403
TI  - Regulation of protein expression by L-arginine in endothelial cells.
AB  - L-Arginine is a conditionally essential amino acid for humans and plays an
      important role in the regulation of cardiovascular function and antioxidative
      defense. Previous studies have focused on the important role of L-arginine as a
      physiological precursor in the generation of nitric oxide and polyamines in
      endothelial cells (cells that line the interior surface of blood vessels).
      Because of the rapid development of high-throughput proteomics technology, there
      is now growing interest in studying roles for L-arginine in modulating
      endothelial-cell protein expression. Of particular interest, recent proteomics
      analysis has shown that treatment of coronary venular endothelial cells with a
      physiological level of L-arginine (e.g., 0.1 mM) increases expression of
      structural proteins (vimentin and tropomyosin) and cytochrome bc1 complex iii
      chain A, while decreasing expression of stress-related proteins (PDZ domain
      containing-3), in these cells. These findings aid in elucidating the mechanisms
      responsible for the beneficial effect of physiological levels of L-arginine on
      the circulatory system.

PMID- 21196404
TI  - Studies of first phase insulin secretion using imposed plasma membrane
      depolarization.
AB  - The first phase of glucose-induced insulin secretion is generally regarded to
      represent the release of a finite pool of secretion-ready granules, triggered by
      the depolarization-induced influx of Ca2+ through L-type Ca2+ channels. However,
      the experimental induction of insulin secretion by imposed plasma membrane
      depolarization may be more complicated than currently appreciated. A comparison
      of the effects of high K+ concentrations with those of KATP channel closure,
      which initiates the electrical activity of the beta cell, suggests that 40 mM K+,
      which is a popular tool to produce a first phase-like secretion, is of
      supraphysiological strength, whereas the 20 mV depolarization by 15 mM K+ is
      nearly inefficient. A major conceptual problem consists in the occurrence of
      action potentials during KATP channel closure, but not during K+ depolarization,
      which leaves the K+ channel conductance unchanged. Recent observations suggest
      that the signal function of the endogenously generated depolarization is not
      homogeneous, but may rather differ between the component mainly determined by
      KATP channel closure (slow waves) and that mainly determined by Ca2+ influx
      (action potentials).

PMID- 21196405
TI  - Apotosis in ovary.
AB  - Folliculogenesis is a complex process involving dramatic morphological and
      functional changes in granulosa and theca cells. This process is sequential and
      dictated specifically by tightly regulated response to endocrine hormones and
      intra-ovarian regulators. In mammalian ovaries, only a few number of presented
      follicles in a fetal ovary can reach ovulatory status during follicular
      development; more than 99% of the follicles in the ovary undergo a degenerative
      process known as "atresia" induced by apotosis. It is characterized by distinct
      biochemical and morphological changes such as DNA fragmentation, plasma membrane
      blebbing and cell volume shrinkage. Apoptosis in ovary is regulated by a number
      of endocrine, locally produced intracellular mediators in a stage-specific and
      time-dependent manner. New knowledge of hormones and cell factors which regulate
      granulosa cell or oocyte apoptosis and their possible signaling pathways
      underlying intracellular events has made important contributions in advancing our
      understanding mechanism of follicular atresia.

PMID- 21196406
TI  - Cryopreservation of cancer-initiating cells derived from glioblastoma.
AB  - Glioblastoma multiforme (GBM) represents the most devastating adult brain tumor.
      GBM follows a hierarchical development in oncogenesis, with a sub-population of
      cells - brain tumor stem cells (BTSCs), exhibiting tumor-initiating potential.
      BTSCs possess extensive self-renewal capability and can repopulate the entire
      tumor mass. They are resistant to conventional therapies, suggesting that they
      are the likely candidates of tumor recurrence. Their eradication is thus
      important for an effective cure. Previous works showed that human-derived BTSCs
      could be stably maintained for 10-15 passages in serum-free condition, and gene
      expression and karyotypic hallmarks similar to the primary tumors were preserved.
      However, primary cells have been shown to sustain additional karyotypic
      aberrations owing to the harsh conditions of extended in vitro serial passage.
      Several investigators have proposed passaging these cells in xenograft models. A
      limitation of such an approach is the inability to return to identical passages
      for experimental repetitions, or the unavailability of suitably-aged mice for
      implantation. We have devised a method to cryopreserve BTSCs and that important
      characteristics were maintained, establishing a repository for drug screening
      endeavors.

PMID- 21196407
TI  - Targeted antioxidant therapies in hyperglycemia-mediated endothelial dysfunction.
AB  - Although intensive glycaemic and blood pressure control have reduced the risks of
      micro- and macrovascular complications, diabetes remains a major cause of
      cardiovascular events, end-stage renal failure, blindness and neuropathy. It is
      therefore imperative to understand the underlying mechanisms and to establish
      effective treatments to prevent, retard or reverse diabetic complications. One
      area of increased focus is the diabetic vascular endothelium. Hyperglycaemia
      triggers a cascade of events, not least an increase in reactive oxygen species
      (ROS) leading to enhanced oxidative stress, with its negative impact on
      endothelial function. In this review, we explore a unifying hypothesis that
      increased glucose-mediated ROS leads to endothelial dysfunction as the
      underpinning causative event triggering accelerated micro- and macrovascular
      complications. In particular, the consequences of deficiencies in the antioxidant
      enzyme, glutathione peroxidase, on endothelial dysfunction as a trigger of
      diabetic micro- and macrovascular complications, will be reviewed. Furthermore,
      novel antioxidant therapies will be highlighted. Specifically, use of Gpx1
      mimetics holds promise as a targeted antioxidant approach and an alternative
      adjunct therapy to reduce diabetic complications.

PMID- 21196408
TI  - The endothelium in compliance and resistance vessels.
AB  - The endothelium is a single layer of cells lining all blood vessels. Although the
      endothelium is not an organ it does, nonetheless have autocrine, paracrine and
      endocrine-like functions that affect the cardiovascular system. Until the
      description in 1980 by Nobel Laureate Robert Furchgott of endothelium-derived
      relaxing factor (EDRF), later identified as nitric oxide (NO), the endothelium
      was considered to be a semi-permeable barrier between the blood and the smooth
      muscle cell layers of the blood vessel. Heterogeneity exists in the functions of
      the endothelium with differences evident between species and between the large
      conduit compliance vessels and the resistance vessels of the microcirculation.
      Endothelial dysfunction, defined as a reduction in the ability of the endothelium
      to transmit a vasodilatation influence on blood flow, has prognostic significance
      and serves as an early indicator of the development of vascular disease as well
      as a therapeutic target. This review compares the role of the endothelium in the
      regulation of vascular tone in conduit versus resistance vessels and how
      alterations in endothelial function may lead to vascular disease.

PMID- 21196409
TI  - Uterine receptivity to implantation of blastocysts in mammals.
AB  - Reproduction in mammals is a highly complex biological process. The critical
      importance of reproduction to propagation of species required the natural
      evolution of various strategies that vary considerably across species. Regardless
      of species, a dialogue between the developing conceptus (embryo-fetus and
      associated placental membranes) and maternal uterus must be established during
      the peri-implantation period. The uterus must provide a microenvironment that
      supports growth and development of the conceptus and is receptive to
      implantation. During the same period, the conceptus must provide its pregnancy
      recognition signaling to sustain the functional life of corpora lutea for
      production of progesterone which is essential for implantation and placentation;
      critical events for successful pregnancy. However, it is within the peri
      implantation period that most embryonic deaths occur due to deficiencies
      attributed to uterine functions or to the failure of the conceptus to develop
      appropriately, signal pregnancy recognition and/or undergo implantation and
      placentation. The challenge is to understand the complexity of key mechanisms
      that are characteristic of successful reproduction in humans and animals and to
      use that knowledge to enhance fertility and reproductive health or to establish
      acceptable methods for control of fertility.

PMID- 21196411
TI  - Skin cancer chemoprevention by alpha-santalol.
AB  - Alpha-santalol, a naturally occurring terpenoid, has been shown to have
      chemopreventive effects on both 7, 12-dimethylbenz(a)anthracene (DMBA)-initiated
      and 12-O- tetradecanoylphorbol-13-acetate (TPA)-promoted skin cancer development
      in CD-1 and SENCAR mice, and UVB-induced skin cancer developments in SKH-1
      hairless mice in a concentration-dependent manner. Studies have demonstrated that
      alpha-santalol could be effective against skin carcinogenesis through both
      induction of apoptosis via caspase activation together with dissipation of
      mitochondria membrane potential and cytochrome c release in A431 cells, and
      inhibition of cell growth via induction of G2/M phase arrest in both A431 cells
      and melanoma UACC-62 cells by altering multiple cell cycle regulatory proteins
      and complexes. This review summarizes the chemopreventive effects and molecular
      mechanisms of alpha-santalol on skin cancer development in both animal models and
      skin cancer cell lines.

PMID- 21196410
TI  - RAGE and its ligands in bone metabolism.
AB  - The receptor for advanced glycation end products (RAGE), a member of the
      immunoglobulin super-family transmembrane proteins, has multiple ligands, thus,
      is implicated in the pathogenesis of various diseases, including diabetic
      complications, neurodegenerative disorders, and inflammatory responses. Its
      function in normal physiology is beginning to be defined, and recent studies have
      pointed to an important role for RAGE and its ligands (e.g., HMGB1 (high mobility
      group box 1)) in innate immune response. In addition, RAGE and its ligands are
      also implicated in osteoclast activation and bone remodeling. Understanding how
      RAGE and its ligands regulate bone remodeling may provide insight into the
      pathogenesis of diabetes and chronic inflammation associated bone loss. Recent
      progress relevant to the functions of RAGE and its ligands in bone remodeling is
      discussed in this review.

PMID- 21196413
TI  - Therapeutic applications of NSAIDS in cancer: special emphasis on tolfenamic
      acid.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are primarily used for the
      treatment of acute or chronic conditions with pain and inflammation. Evidence
      from a wide range of sources suggested that chronic administration of NSAIDs
      reduced the risk of cancer incidences. Both the epidemiological and animal
      studies showed an inverse association between the incidence of various cancers
      and the use of aspirin or other NSAIDs. The chemopreventive and therapeutic
      interventions of NSAIDs in cancer are obvious; however, the instigation of drug
      and treatment period depends on the study objective. Typically, prevention
      involves initiating the medication before the appearance of clinical symptoms and
      lasts long-term; while treatment could be short-term and contingent to the
      response of patient to the medication. Recent studies from our laboratories
      provided substantial evidence on the anti-cancer activity of tolfenamic acid, a
      NSAID for the potential applications in pancreatic, esophageal and lung cancers.
      In this review, we provide a summary on the potential benefits of NSAIDs in a
      variety of human cancers with more emphasis on tolfenamic acid.

PMID- 21196412
TI  - Integrin-linked kinase 1: role in hormonal cancer progression.
AB  - Integrin-linked kinase 1 (ILK1) is a serine/threonine kinase that plays important
      roles in a variety of cellular functions including cell survival, migration and
      angiogenesis. ILK1 is normally expressed in numerous tissues and activated by
      growth factors, cytokines and hormones. Dysregulation of ILK1 expression or
      function is found in several hormonal tumors including breast, ovary and
      prostate. Emerging evidence suggests that ILK overexpression promotes cellular
      transformation, cell survival, epithelial mesenchymal transition (EMT), and
      metastasis of hormonal cancer cells while inhibition of ILK1 reduces tumor growth
      and progression. The recent development of ILK1 inhibitors has provided novel
      mechanisms for blocking ILK1 signaling to curb metastasis and therapy resistance
      of hormonal tumors. This review will focus on recent advances made towards
      understanding the role of ILK signaling axis in progression of hormonal cancer.

PMID- 21196414
TI  - ShRNA-targeted MAP4K4 inhibits hepatocellular carcinoma growth.
AB  - PURPOSE: Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) is
      overexpressed in many types of cancer. Herein, we aimed to investigate its
      expression pattern, clinical significance, and biological function in
      hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: MAP4K4 expression was
      examined in 20 fresh HCCs and corresponding nontumor liver tissues.
      Immunohistochemistry for MAP4K4 was performed on additional 400 HCCs, of which
      305 (76%) were positive for hepatitis B surface antigens. The clinical
      significance of MAP4K4 expression was analyzed. MAP4K4 downregulation was
      performed in HCC cell lines HepG2 and Hep3B with high abundance of MAP4K4, and
      the effects of MAP4K4 silencing on cell proliferation in vitro and tumor growth
      in vivo were evaluated. Quantitative real-time PCR arrays were employed to
      identify the MAP4K4-regulated signaling pathways. RESULTS: MAP4K4 was aberrantly
      overexpressed in HCCs relative to adjacent nontumor liver tissues. This
      overexpression was significantly associated with larger tumor size, increased
      histologic grade, advanced tumor stage, and intrahepatic metastasis, as well as
      worse overall survival and higher early recurrence rate. Knockdown of the MAP4K4
      expression reduced cell proliferation, blocked cell cycle at S phase, and
      increased apoptosis. The antitumor effects of MAP4K4 silencing were also observed
      in vivo, manifested as retarded tumor xenograft growth. Furthermore, multiple
      tumor progression-related signaling pathways including JNK, NFkappaB, and toll
      like receptors were repressed by MAP4K4 downregulation. CONCLUSIONS: MAP4K4
      overexpression is an independent predictor of poor prognosis of HCC patients, and
      inhibition of its expression might be of therapeutic significance.

PMID- 21196415
TI  - EGFR-homing dsRNA activates cancer-targeted immune response and eliminates
      disseminated EGFR-overexpressing tumors in mice.
AB  - PURPOSE: The cause of most cancer deaths is incurable dissemination of cancer
      cells into vital organs. Current systemic therapies for disseminated cancers
      provide limited efficacy and are often accompanied by toxic side effects. We have
      recently shown that local application of epidermal growth factor receptor (EGFR)
      targeted polyinosine-cytosine (polyIC) eradicates preestablished EGFR
      overexpressing tumors. Here we show for the first time the high efficiency of
      systemic application of polyIC/melittin-polyethyleneimine-polyethyleneglycol-EGF
      (polyIC/MPPE) in combination with human immune cells. EXPERIMENTAL DESIGN: Cancer
      targeted activation of immune cells was examined in vitro and in vivo following
      transfection with polyIC/MPPE. The therapeutic efficiency of the strategy was
      then examined on disseminated EGFR-overexpressing tumors grown in severe combined
      immunodeficient (SCID) mice. RESULTS: Intravenous delivery of polyIC/MPPE
      followed by intraperitoneal injection of peripheral blood mononuclear cells
      induced the complete cure of SCID mice with preestablished disseminated EGFR
      overexpressing tumors, with no adverse toxic effects. The immune cells and the
      cytokines they produce are localized to the tumor site of the treated animal and
      contribute decisively to the demise of the tumor cells. The immune system homes
      to the tumors, due to the chemokines produced by the internalized polyIC.
      CONCLUSION: The EGFR-homing vector loaded with polyIC can be used to treat and
      possibly cure patients with disseminated EGFR-overexpressing tumors. The
      possibility of adopting this strategy to treat other tumors that express a
      protein capable of ligand induced internalization is discussed.

PMID- 21196416
TI  - A case of childhood subcutaneous pyogenic granuloma (lobular capillary
      hemangioma).

PMID- 21196417
TI  - Parent preferences for pediatric influenza vaccine attributes.
AB  - Influenza vaccine is available as an intramuscular injection or an intranasal
      spray for eligible children. This study was conducted to examine parents'
      preferences for influenza vaccine attributes and the attributes' relative
      importance regarding the vaccination of their children. A quantitative Web survey
      was administered to 500 parents of children aged 2 to 12 years. The survey
      included general preference questions and conjoint (trade-off) questions. Parents
      most frequently selected efficacy, risk of temporary side effects, and physician
      recommendation as important vaccine attributes from a provided list (92%, 75%,
      and 59%, respectively). For attributes selected as important, parents rated the
      importance of the attribute; the highest mean importance ratings were given to
      efficacy, presence of mercury-containing preservative, and physician
      recommendation.The highest relative importance ratings in the conjoint section
      were given to efficacy and presence of mercury-containing preservative. Parental
      education on influenza vaccine efficacy and safety may help to improve pediatric
      vaccination rates.

PMID- 21196418
TI  - Physician "costs" in providing behavioral health in primary care.
AB  - OBJECTIVE: To examine pediatricians time spent, and resulting reimbursement
      payments for, addressing behavioral health concerns in a rural primary care
      pediatric practice. METHODS: Research assistants observed 228 patient visits in a
      rural pediatric primary care office. The length of the visit (in minutes),
      content of visit, number and type of codes billed, and related insurance
      reimbursement amounts were recorded. Interrater reliability, scored for 22% of
      patient visits, was >=90%. RESULTS: Medical only visits lasted, on average, 8
      minutes as compared with behavioral only visits that required nearly 20 minutes
      of physician time. Pediatricians billed up to 10 different billing codes for
      medical only visits but only billed 1 code for behavioral only visits.
      Consequently, pediatricians were reimbursed significantly less, per minute, for
      behavioral only visits as compared with those sessions addressing medical only or
      a combination of medical and behavior concerns. CONCLUSION: Findings converge
      with previous research, demonstrating that behavioral health concerns
      dramatically affect the length of visit for primary care physicians. Moreover,
      this study is the first to document the specific impact of such concerns on
      pediatrician reimbursement for providing behavioral services. These results
      provide further support for integrating behavioral health services into pediatric
      primary care settings, thus allowing physicians to refer more difficult patients
      with behavioral issues to in-house collaborating behavioral health providers who
      can spend additional time necessary to address the behavioral health issue and
      who are licensed to receive mental health reimbursement.

PMID- 21196419
TI  - Epidemiology of player--player contact injuries among US high school athletes,
      2005-2009.
AB  - OBJECTIVE: To investigate the epidemiology of player-player contact injuries in a
      nationally representative sample of US high school student-athletes. METHODS:
      Data from the National High School Sports-Related Injury Surveillance Study were
      analyzed to calculate rates, describe patterns, and evaluate potential risk
      factors for player-player contact injuries. RESULTS: Player-player contact
      injuries represented 46.4% of all high school sports injuries and occurred at a
      rate of 11.6 per 10,000 athlete exposures (AEs). Player-player contact injury
      rates (per 10 000 AEs) were highest in football (26.0), wrestling (10.8), and
      girls' soccer (9.8). Body sites most commonly injured were the ankle/foot
      (21.9%), head/face (18.9%), and knee (16.9%). Most common diagnoses were ligament
      sprains (32.5%). CONCLUSIONS: Player-player contact is the most common mechanism
      of injury among high school athletes. The epidemiology of such injuries varies by
      gender and sport. Developing effective preventive measures depends on increasing
      our knowledge of player-player contact injury rates, patterns, and risk factors.

PMID- 21196420
TI  - Exercise program adherence using a 5-kilometer (5K) event as an achievable goal
      in people with schizophrenia.
AB  - People with schizophrenia have a higher prevalence of obesity than the general
      population. Many people with this illness struggle with weight gain, due, in
      part, to medications and other factors that act as obstacles to exercise and
      healthy eating. Several studies have shown the benefits of behavioral weight loss
      programs targeting eating and/or exercise in people with schizophrenia. Fewer
      studies have used competitive events as a goal for an exercise program. The
      current study tested the feasibility of preparing, using an exercise program, for
      a 5-kilometer (5K) event in people with schizophrenia. The exercise program was a
      10-week training program consisting of three supervised walking/jogging sessions
      per week and a weekly educational meeting on healthy behaviors. Almost 65%
      (11/17) of the subjects participated in all of the training sessions, and 82%
      (14/17) participated in the 5K event. Participants did not gain a significant
      amount of weight during the exercise program (median weight change = 0.7 kg; 25th
      percentile 0.5, 75th percentile 3.9, p = .10). This study suggests that using an
      achievable goal, such as a 5K event, promotes adherence to an exercise program
      and is feasible in a population of people with chronic schizophrenia.

PMID- 21196421
TI  - Integrating genomics into biobehavioral research: a transplantation exemplar.
AB  - Biobehavioral research is becoming more established in nursing. This research
      paradigm includes a focus on the interactions of biological and behavioral
      variables and their impact on health outcomes. Nurse researchers have
      incorporated genomics as a research focus. However, biobehavioral and genomic
      approaches have often been viewed as separate paradigms. This article provides
      research exemplars from the liver transplantation population to illustrate how
      genomics can be integrated into a biobehavioral model of nursing research.
      Examples of how this integrated approach may be utilized to address gaps of
      knowledge are provided.

PMID- 21196422
TI  - Effects of using a high-density foam pad versus a viscoelastic polymer pad on the
      incidence of pressure ulcer development during spinal surgery.
AB  - The purpose of this study was to evaluate the effect of high-density foam (HDF)
      pads versus viscoelastic polymer (VP) pads in the prevention of pressure ulcer
      formation during spinal surgery and their cost-effectiveness. Subjects were 30
      patients who underwent spinal surgery for more than 3 hr in a prone position. One
      side of the chest and iliac crest was padded with HDF pads and the other side was
      padded with VP pads. An Xsensor(r) pressure measuring sheet was placed between
      the pad and the patient. Bilateral chest and iliac crest points were observed for
      the presence of pressure ulcers at 30 min after the operation. Results showed
      that a pressure ulcer had occurred at 9 of 120 compression points (7.5% of the
      total), 30 min after the operation. Risk evaluation showed that female gender,
      weight <50 kg, and body mass index (BMI) <18 kg/m(2) as well as location (the
      iliac crest) were all risk factors for development of pressure ulcers. The most
      significant factor was BMI <18 kg/m(2). The average and peak pressures measured
      at the points padded with the VP pads were significantly lower than those padded
      with the HDF pads. However, there was no significant difference between the VP
      and the HDF pads regarding ulcer prevention. Because the cost of a VP pad is 250
      times greater than that of an HDF pad of similar size, the VP pad should only be
      considered for use in high-risk patients.

PMID- 21196423
TI  - Is childhood abuse or neglect associated with symptom reports and physiological
      measures in women with irritable bowel syndrome?
AB  - PURPOSE: Early childhood traumatic experiences (e.g., abuse or neglect) may
      contribute to sleep disturbances as well as to other indicators of arousal in
      patients with irritable bowel syndrome (IBS). This study compared women with IBS
      positive for a history of childhood abuse and/or neglect to women with IBS
      without this history on daily gastrointestinal (GI), sleep, somatic, and
      psychological symptom distress, polysomnographic sleep, urine catecholamines
      (CAs) and cortisol, and nocturnal heart rate variability (HRV). METHODS: Adult
      women with IBS recruited from the community were divided into two groups: 21 with
      abuse/neglect and 19 without abuse/neglect based on responses to the Childhood
      Trauma Questionnaire (CTQ; physical, emotional, sexual abuse, or neglect). Women
      were interviewed, maintained a 30-day symptom diary, and slept in a sleep
      laboratory. Polysomnographic and nocturnal HRV data were obtained. First-voided
      urine samples were assayed for cortisol and CA levels. RESULTS: Women with IBS
      positive for abuse/neglect history were older than women without this history.
      Among GI symptoms, only heartburn and nausea were significantly higher in women
      with abuse/neglect. Sleep, somatic, and psychological symptoms were significantly
      higher in women in the abuse/neglect group. With the exception of percentage of
      time in rapid eye movement (REM) sleep, there were few differences in sleep-stage
      variables and urine hormone levels. Mean heart rate interval and the natural log
      of the standard deviation of RR intervals for the entire sleep interval (Ln SDNN)
      values were lower in those who experienced childhood abuse/neglect. CONCLUSION:
      Women with IBS who self-report childhood abuse/neglect are more likely to report
      disturbed sleep, somatic symptoms, and psychological distress. Women with IBS
      should be screened for adverse childhood events including abuse/neglect.

PMID- 21196424
TI  - Evaluating the role of serotonin on neuropsychological function after breast
      cancer using acute tryptophan depletion.
AB  - Although cognitive dysfunction is a prevalent and disruptive problem for many
      breast cancer survivors (BCSs), little research has examined its etiology. One
      potential mechanism that remains to be explored is serotonin. Serotonin has been
      implicated in normal and dysfunctional cognitive processes, and serotonin levels
      are significantly affected by estrogen withdrawal, a common side effect of breast
      cancer treatment. However, no study has evaluated serotonin's role on cognitive
      dysfunction in BCSs. The purpose of this study was to examine the role of
      serotonin in cognitive dysfunction in survivors by lowering central serotonin
      concentrations via acute tryptophan depletion (ATD). Based on previous research
      in noncancer populations, we hypothesized that alterations in central serotonin
      levels would induce cognitive dysfunction in these women controlling for
      confounding characteristics such as fluctuating mood and glucose levels.
      Secondarily, we explored whether genetic variations in serotonin genes would
      partly explain ATD. Participants included 20 female BCSs, posttreatment for
      nonmetastatic breast cancer, who received ATD or control in a double-blind,
      crossover design. Cognitive performance was measured at the 5-hr
      tryptophan/serotonin nadir on each test day using standardized neuropsychological
      tests. Specific impairment was noted in episodic memory (delayed recall) and
      motor speed during ATD versus control. ATD did not alter new learning (immediate
      recall), working memory, verbal fluency, or information processing speed.
      Findings suggest that serotonin may play a critical role in memory consolidation
      and motor functioning in BCSs.

PMID- 21196425
TI  - To explore relationships between physiological stress signals and stress
      behaviors in preterm infants during periods of exposure to environmental stress
      in the hospital.
AB  - The purpose of this exploratory descriptive study was to examine relationships
      among physiological stress signals (heart rate (HR), respiratory rate (RR), and
      oxygen saturation) and stress behaviors (6 stress behaviors related to sleep-wake
      states, 10 self-regulatory behaviors, and 17 behavioral stress cues) in preterm
      infants during periods of environmental stress. This research used a prospective
      repeated-measures design in a convenience sample of preterm infants of <37 weeks'
      gestational age and <28 days' postnatal age. All infants were in the incubator in
      a neonatal intensive care unit or a sick baby care unit in one of two hospitals
      at the time of data collection. Multiple linear regressions of generalized
      estimating equations were used to determine relationships. Variables were
      measured every 2 min over 4 hr, for a total of 4,164 observations in 37 preterm
      infants. There were statistically significant relationships between 9 stress
      behavioral responses and changes in HR (seven stress behaviors and two self
      regulatory behaviors; p < .05), between 9 stress behavioral responses and changes
      in RR (seven stress behaviors and two self-regulatory behaviors; p < .05), and
      between 11 stress behavioral responses and changes in oxygen saturation (seven
      stress behaviors and four self-regulatory behaviors; p < .05). Findings
      demonstrate that the functions of self-regulatory behaviors and some special
      behaviors in preterm infants during environmental stress are related to
      physiological stress signals. However, results should be investigated further in
      larger samples.

PMID- 21196426
TI  - Acute effects of walking environment and GSTM1 variants in children with asthma.
AB  - BACKGROUND: Exercise in air polluted by traffic emissions may aggravate airway
      inflammation in children with asthma, particularly those who produce decreased
      glutathione-S transferase (GST) as a result of GSTM1 gene deletion. OBJECTIVES:
      This pilot crossover study investigated whether children with asthma experience
      more airway changes when exercising outdoors near roadways than when exercising
      indoors. It also examined differences in risk between children with and without
      GSTM1 deletion. METHOD: Children between the ages of 5 and 12 years were assigned
      to groups and walked daily for 1 week in each exercise condition. Airway
      inflammation indicated by exhaled nitric oxide (eNO) and pulmonary functions
      measured as forced expiratory volume in 1 s (FEV1) and mid-expiratory flow rate
      were measured at baseline and at three intervals during the walking program.
      Independent variables of interest included walking condition (place), time of
      walking, genotype, and particulate matter (PM) exposure. RESULTS: A linear mixed
      models approach was used to investigate the contributions of targeted variables
      to respiratory outcomes. Results indicated that walking location and ambient
      level of ultrafine particulates during walking influenced function of small
      airways. Absence of one or both alleles for the GSTM1 gene did not influence
      airway function acutely. DISCUSSION: Mid-expiratory flow (FEF(25-75)) may be more
      informative than FEV1 in studies of acute lung function changes in children with
      asthma. Further study of the effects of varied environmental conditions on lower
      airway function of children is needed to optimize exercise experiences for urban
      children with asthma.

PMID- 21196427
TI  - Effects of sleep loss and strenuous physical activity on the rest-activity
      circadian rhythm: a study on 500 km and 1,000 km dogsled racers.
AB  - OBJECTIVE: Rest-activity circadian rhythm is strongly linked to an organism's
      entrainment. Sleep loss and prolonged fatigue could affect the circadian system,
      inducing neurobehavioral deficits. The Finnmarkslopet is Europe's longest dogsled
      race. In this competition, lasting up to 7 days, participants (mushers) are
      physically active most of the time, having little and fragmented rest. Therefore,
      the race provides an opportunity to investigate the effects of prolonged fatigue
      and sleep loss. METHODS: Ten mushers, participating in the 500 km and 1,000 km
      categories, underwent continuous actigraph monitoring (5 days) before and after
      the race. During the competition, heart rate (HR) was recorded by an HR monitor.
      RESULTS: There was a reduction in the average activity values during the 24-hr
      cycle after the race. Although there were signs of a forward phase shift, these
      were weak and unstable. Nonparametric circadian rhythm analysis (NPCRA) showed
      reductions in interdaily stability (IS) and relative amplitude (RA). 1,000 km
      mushers also showed sleep disturbances. CONCLUSION: A period of 3 days of little
      and fragmented sleep (3-4 hr of total rest per day), in which subjects were
      engaged in a prolonged physical effort, was enough to significantly affect the
      rest-activity rhythm. A longer period (5 days) in such a condition induced even
      more accentuated alterations, with a disturbance in nocturnal sleep. Disrupted
      sleep is common among hospitalized patients and those working long shifts. This
      study demonstrates changes in the structure of the rest-activity circadian rhythm
      that can result and may suggest opportunities for intervention.

PMID- 21196428
TI  - Randomized crossover trial of kangaroo care to reduce biobehavioral pain
      responses in preterm infants: a pilot study.
AB  - Kangaroo care (KC), skin-to-skin contact between mother and infant, is a
      promising method for blunting pain responses. This crossover pilot tested KC
      effects on biobehavioral responses to heel stick in preterm infants (30-32 weeks'
      gestational age, 2-9 days old) measured by Premature Infant Pain Profile (PIPP)
      and salivary and serum cortisol. Mother-infant dyads were randomly assigned to KC
      heel stick (KCH) first or incubator heel stick (IH) first. Study 1 (80-min study,
      N = 18) tested the effect of 80 min of KC before and throughout the heel stick
      procedure versus incubator care. Study 2 (30-min study, N = 10) tested 30 min of
      KC before and throughout the heel stick versus incubator care. KCH and IH began
      during a premeasurement phase and continued through four data collection phases:
      baseline, heel warming, heel stick, and recovery. PIPP responses were measured
      every 30 s during data collection; salivary cortisol was measured at the end of
      baseline and recovery; and serum cortisol was measured during heel stick. Study 1
      showed no differences between KCH and IH. Study 2 showed lower PIPP scores at
      four time points during recovery (p < .05 to p < .001), lower salivary cortisol
      at the end of recovery (p < .05), and lower serum cortisol during heel stick for
      the KCH condition (p < .05) as well as clinically lower PIPP scores in the KCH
      condition during heel stick. Thirty minutes of KC before and throughout the heel
      stick reduced biobehavioral responses to pain in preterm infants.

PMID- 21196429
TI  - Joint modeling of longitudinal data in multiple behavioral change.
AB  - Multiple behavioral change is an exciting and evolving research area, albeit one
      that presents analytic challenges to investigators. This manuscript considers the
      problem of modeling jointly trajectories for two or more possibly non-normally
      distributed dependent variables, such as marijuana smoking and risky sexual
      activity, collected longitudinally. Of particular scientific interest is applying
      such modeling to elucidate the nature of the interaction, if any, between an
      intervention and personal characteristics, such as sensation seeking and
      impulsivity. The authors describe three analytic approaches: generalized linear
      mixed modeling, group-based trajectory modeling, and latent growth curve
      modeling. In particular, the authors identify identify the strengths and
      weaknesses of these analytic approaches and assess their impact (or lack thereof)
      on the psychological and behavioral science literature. The authors also compare
      what investigators have been doing analytically versus what they might want to be
      doing in the future and discuss the implications for basic and translational
      research.

PMID- 21196430
TI  - Assessing costs and potential returns of evidence-based programs for seniors.
AB  - The authors describe the customary tools used by health services researchers to
      conduct economic evaluations of health interventions. Recognizing the inherent
      challenges of these tools for utilization in contemporary public health practice,
      we recommend a practical cost-benefit analysis (PCBA) to allow public health
      practitioners to assess the economic merits of their existing public health
      programs. The PCBA estimates what health effects and corresponding medical cost
      avoidance would be required to support the costs associated with implementing a
      community-based prevention program. We apply the PCBA to evaluate a statewide
      evidence-based falls prevention program for seniors in Texas. We estimate a
      positive return on realized costs due to avoided direct and indirect medical
      expenses if the program averts 7 falls among 140 participants within the first
      year. While acknowledging the demonstrated health-related benefits of public
      health interventions, we provide a practical ex-post economic evaluation
      methodology to assess return on investment as a more simplistic yet effective
      alternative for public health practitioners versus contemporary analyses of
      health services researchers.

PMID- 21196431
TI  - Isolinderanolide B, a butanolide extracted from the stems of Cinnamomum
      subavenium, inhibits proliferation of T24 human bladder cancer cells by blocking
      cell cycle progression and inducing apoptosis.
AB  - Isolinderanolide B (IOB), a butanolide extracted from the stems of Cinnamomum
      subavenium, was investigated for its antiproliferative activity in T24 human
      bladder cancer cells. To identity the anticancer mechanism of IOB, its effect on
      apoptosis, cell cycle distribution, and levels of p53, p21 Waf1/Cip1, Fas/APO-1
      receptor, and Fas ligand was assayed. Enzyme-linked immunosorbent assay showed
      that the G0/G1 phase arrest is because of increase in the expression of p21
      Waf1/Cip1. An enhancement in Fas/APO-1 and membrane-bound Fas ligand (mFasL)
      might be responsible for the apoptotic effect induced by IOB. This study reports
      the novel finding that the induction of p21 Waf1/Cip1 and activity of the
      Fas/mFas ligand apoptotic system may participate in the antiproliferative
      activity of IOB in T24 cells.

PMID- 21196432
TI  - Exploiting tyrosinase expression and activity in melanocytic tumors: quercetin
      and the central role of p53.
AB  - Melanoma is an aggressive tumor that expresses the pigmentation enzyme
      tyrosinase. Tyrosinase expression increases during tumorigenesis, which could
      allow for selective treatment of this tumor type by strategies that use
      tyrosinase activity. Approaches targeting tyrosinase would involve gene
      transcription or signal transduction pathways mediated by p53 in a direct or
      indirect manner. Two pathways are proposed for exploiting tyrosinase expression:
      (a) a p53-dependent pathway leading to apoptosis or arrest and (b) a reactive
      oxygen species-mediated induction of endoplasmic reticulum stress in p53 mutant
      tumors. Both strategies could use tyrosinase-mediated activation of quercetin, a
      dietary polyphenol that induces the expression of p53 and modulates reactive
      oxygen species. In addition to antitumor signaling properties, activation of
      quercetin could complement conventional cancer therapy by the induction of phase
      II detoxification enzymes resulting in p53 stabilization and transduction of its
      downstream targets. In conclusion, recent advances in tyrosinase enzymology,
      prodrug chemistry, and modern chemotherapeutics present an intriguing and
      selective multitherapy targeting system where dietary bioflavonoids could be used
      to complement conventional cancer treatments.

PMID- 21196433
TI  - Rehabilitation in neuro-oncology: a meta-analysis of published data and a mono
      institutional experience.
AB  - BACKGROUND: Rehabilitation for cancer patients with central nervous system (CNS)
      involvement is rarely considered and data on its use are limited. The purpose of
      the present study is to collect all available published data on neuro-oncology
      rehabilitation and perform a meta-analysis where results were presented in a
      comparable manner. Moreover, the authors report results on cancer patients with
      neurological disabilities undergoing rehabilitation at their unit. STUDY DESIGN:
      A PubMed search was performed to identify studies regarding cancer patients with
      CNS involvement undergoing inpatient physical rehabilitation. Studies with a
      complete functional evaluation at admission and discharge were selected. As the
      most common evaluation scales were Functional Independence Measure (FIM) and
      Barthel Index (BI), only articles with complete FIM and/or BI data were selected
      for the meta-analysis. Moreover, 23 cancer patients suffering from diverse
      neurological disabilities underwent standard rehabilitation program between April
      2005 and December 2007 at the San Raffaele Pisana Rehabilitation Center. Patient
      demographics and relevant clinical data were collected. Motricity Index, Trunk
      Control Test score, and BI were monitored during rehabilitation to assess patient
      progresses. BI results of patients in this study were included in the meta
      analysis. RESULTS: The meta-analysis included results of a total of 994 patients.
      A statistically significant (P < .05) improvement of both BI and FIM scores was
      demonstrated after rehabilitation (standardized mean difference = 0.60 and 0.75,
      respectively). Functional status determined by either FIM or BI improved on
      average by 36%. CONCLUSION: Published data demonstrate that patients with brain
      tumors undergoing inpatient rehabilitation appear to make functional gains in
      line with those seen in similar patients with nonneoplastic conditions.

PMID- 21196434
TI  - Sexual assault programming on college campuses: using social psychological belief
      and behavior change principles to improve outcomes.
AB  - Sexual assault programming is often delivered without a theoretical framework and
      does not typically utilize applicable research that could help to induce change
      among participants. Such interventions may target male and/or female students,
      although the focus of this review is on men. It is important to examine these
      programs in light of current theoretical knowledge and empirical findings from
      the social psychological attitudinal and behavioral change literatures. To this
      end, current programming efforts and their limitations are briefly reviewed.
      Three social psychological theories targeting belief and behavior change (i.e.,
      social norms, hypocrisy salience, decision, and deterrents) are discussed and
      their application to such programming is elaborated. Given this information,
      recommendations for the research and practice of such interventions are provided.

PMID- 21196435
TI  - Aftercare services for international sex trafficking survivors: informing U.S.
      service and program development in an emerging practice area.
AB  - International sex trafficking into the United States appears to be a serious and
      growing problem, although the evidence regarding prevalence, risk, and
      consequences is incomplete. Nonetheless, human service providers are increasingly
      being asked to offer services to sex trafficking survivors. Consequently,
      providers need information to guide services and program development in this
      emerging practice area. To address this knowledge need, we systematically
      reviewed and synthesized 20 documents addressing the needs of and services for
      international survivors of sex trafficking into the United States. The main
      finding from the review shows the importance of a continuum of aftercare services
      to address survivors' changing needs as they move from initial freedom to
      recovery and independence. Based on our synthesis of the reviewed literature, we
      present a service delivery framework to guide providers' development of services
      for survivors.

PMID- 21196436
TI  - College- or university-based sexual assault prevention programs: a review of
      program outcomes, characteristics, and recommendations.
AB  - This article examines literature reviews of research articles and dissertations
      focused on the effectiveness of college- or university-based sexual violence
      prevention programs. Literature reviews were eligible for inclusion in this
      article if they examined empirical published peer-reviewed research articles or
      dissertation research that reported original data; focused on examining the
      effectiveness of programs that were developed to reduce sexual violence that
      occurred in college or university settings; offered recommendations for
      developing and implementing effective college- or university-based sexual assault
      prevention programs; and reviewed studies that occurred in the United States.
      Eight review articles met the inclusion criteria. The results suggest that the
      effectiveness of college- or university-based sexual violence prevention programs
      varies depending on the type of audience, facilitator, format, and program
      content. Recommendations from existing reviews of empirical research concerning
      these program characteristics should be considered by college or university
      administrators when designing and implementing their own programs on campus.

PMID- 21196437
TI  - Tracking cognition-health changes from 55 to 95 years of age.
AB  - OBJECTIVES: Among the key targets of inquiry in cognitive aging are (1) the
      description of cognitive changes with advancing age and (2) the association of
      such cognitive changes with modulating factors in the changing epidemiological
      context. METHODS: In the current study, we assemble multi-occasion (up to 12
      years) cognitive (speed, episodic memory, and semantic memory) and self-reported
      health data from the Victoria Longitudinal Study (n = 988; ages 55-95 years).
      RESULTS: The results from piecewise random effects models using age as a basis
      indicated that only selected measures of episodic memory and semantic memory
      showed evidence of significant declines prior to age 75. After age 75, all
      cognitive abilities showed evidence for statistically significant declines,
      although the magnitude of these changes varied considerably. Performance at age
      75 was correlated with self-reported health for measures of processing speed and
      episodic memory. Changes in health status were related to changes in some aspects
      of processing speed. DISCUSSIONS: The results indicated that (1) for many
      cognitive abilities declines in performance did not manifest until after age 75
      and (2) self-reported health was related to level of performance more than
      changes over age.

PMID- 21196438
TI  - Histories of social engagement and adult cognition: midlife in the U.S. study.
AB  - OBJECTIVES: To evaluate whether social contacts, support, and social
      strain/conflict are related to executive function and memory abilities in middle
      age and older adults. METHODS: Longitudinal data on social contacts, support, and
      strain/conflict were examined in relation to executive function and memory at
      ages 35-85 years using data from the national Midlife in the U.S. (MIDUS) study.
      Age-related differences in patterns of association were also examined. RESULTS:
      Regression analyses, controlling for age, sex, race, education, chronic health
      conditions, and health behaviors, revealed significant positive associations
      between histories of greater social contacts and support and both executive
      function and episodic memory, whereas declines in social contacts were negatively
      associated with both outcomes. Greater average reported frequency of social
      exchanges characterized by strain or conflict was negatively associated with
      executive function but not episodic memory. Patterns were generally consistent
      across different age groups; where differences were seen, associations were
      stronger in younger age group. DISCUSSION: Positive and negative aspects of
      social relationships are related to cognition throughout adulthood, consistent
      with the hypothesis that social factors have life-long influences on cognition.
      Positive and negative aspects of social engagement may thus be important factors
      to consider in relation to efforts to promote optimal cognitive development and
      cognitive aging.

PMID- 21196439
TI  - Correlation of basal EGFR expression with pancreatic cancer grading but not with
      clinical outcome after gemcitabine-based treatment.

PMID- 21196440
TI  - HER2 and response to anthracycline-based neoadjuvant chemotherapy in breast
      cancer.
AB  - BACKGROUND: The predictive role of human epidermal growth factor receptor 2
      (HER2) to adjuvant anthracycline-based chemotherapy remains controversial. Here,
      we investigated the association between HER2 status and pathological response in
      breast cancer patients who received neoadjuvant anthracycline-based regimens.
      PATIENTS AND METHODS: Women (n = 538) with operable primary breast cancer
      received neoadjuvant anthracycline-based chemotherapy. Pathological complete
      response (pCR) was defined as no invasive breast tumor cells in breast after
      completion of neoadjuvant chemotherapy. HER2 status was determined by
      immunohistochemistry and/or by fluorescence in situ hybridization in core biopsy
      breast cancer tissue obtained before initiation of neoadjuvant chemotherapy.
      RESULTS: In this cohort of 538 patients, 23.9% of patients achieved a pCR in
      their breast. HER2-positive tumors had a lower rate of pCR than did HER2-negative
      tumors (14.7% versus 25.7%, P = 0.013); negative HER2 status remained as an
      independent favorable predictor of pCR after adjusted for age, estrogen receptor,
      progesterone receptor, tumor size, chemotherapy cycles, and tumor grade in a
      multivariate analysis (odds ratio = 3.14; 95% confidence interval = 1.60-6.16, P
      = 0.001). Furthermore, patients with a pCR had a higher 3-year disease-free
      survival (DFS) rate than did patients without a pCR (P = 0.007). CONCLUSION:
      Women with HER2-negative breast cancers rather than HER2-positive tumors benefit
      from anthracycline-based neoadjuvant chemotherapy.

PMID- 21196442
TI  - Comparison of haemodialysis patients and non-haemodialysis patients with respect
      to clinical characteristics and 3-year clinical outcomes after sirolimus-eluting
      stent implantation: insights from the Japan multi-centre post-marketing
      surveillance registry.
AB  - AIMS: Long-term outcomes after sirolimus-eluting stent (SES) implantation in
      haemodialysis (HD) patients have remained controversial. We investigated the
      impact of HD on outcomes after SES implantation. METHODS AND RESULTS: We analysed
      the data on 2050 patients who underwent SES implantation in a multi-centre
      prospective registry in Japan. Three-year clinical outcomes were compared between
      the HD group (n = 106) and the non-haemodialysis (NH) group (n = 1944). At the 3
      year clinical follow-up, the rates of unadjusted cardiac mortality (HD: 16.3 vs.
      NH: 2.3%) and target-lesion revascularization (TLR) (HD: 19.4 vs. NH: 6.6%) were
      significantly higher in the HD group than the NH group (P < 0.001). Although HD
      group had a numerically higher stent thrombosis rate, the difference in stent
      thrombosis between the two groups (HD: 2.0 vs. NH: 0.7%) did not reach
      statistical significance. Using Cox's proportional-hazard models with propensity
      score adjustment for baseline differences, the HD group had higher risks of TLR
      [HD: 16.3 vs. NH: 6.1%; hazard ratio, 2.83; 95% confidence interval (CI): 1.62
      4.93, P = 0.0003] and cardiac death (HD: 12.3 vs. NH: 2.3%; hazard ratio, 5.51;
      95% CI: 2.58-11.78, P < 0.0001). The consistent results of analyses, whether
      unadjusted or adjusted for other baseline clinical and procedural differences,
      identify HD as an independent risk factor for cardiac death and TLR. CONCLUSIONS:
      Percutaneous coronary intervention with SES in HD patients has a higher incidence
      of repeat revascularization and mortality compared with those in NH patients.
      Haemodialysis appears to be strongly associated with mortality and repeat
      revascularization even after SES implantation.

PMID- 21196441
TI  - Phase III trial of CHOP-21 versus CHOP-14 for aggressive non-Hodgkin's lymphoma:
      final results of the Japan Clinical Oncology Group Study, JCOG 9809.
AB  - BACKGROUND: CHOP-21 has remained the standard chemotherapy for aggressive non
      Hodgkin's lymphoma (NHL), and dose intensification is a potential strategy for
      improving therapeutic results. We conducted a phase III trial to determine
      whether dose-dense strategy involving interval shortening of CHOP (CHOP-14) is
      superior to CHOP-21. PATIENTS AND METHODS: A total of 323 previously untreated
      patients (aged 15-69 years) with stages II-IV aggressive NHL were randomized. The
      primary end point was progression-free survival (PFS). RESULTS: Treatment
      compliance was comparable in both study arms. At 7-year follow-up, no substantial
      differences were observed in PFS and overall survival (OS) between CHOP-21 (n =
      161) and CHOP-14 (n = 162) arms. Median PFS was 2.8 and 2.6 years with CHOP-21
      and CHOP-14, respectively (one-sided log-rank P = 0.79). Eight-year OS and PFS
      rates were 56% and 42% [95% confidence interval (CI) 47% to 64% and 34% to 49%],
      respectively, with CHOP-21 and 55% and 38% (95% CI 47% to 63% and 31% to 46%),
      respectively, with CHOP-14. Subgroup analyses showed no remarkable differences in
      PFS or OS for patients stratified as per the International Prognostic Index or by
      age. CONCLUSION: Dose-intensification strategy involving interval shortening of
      CHOP did not prolong PFS in advanced, aggressive NHL.

PMID- 21196443
TI  - Impact of hospital proportion and volume on primary percutaneous coronary
      intervention performance in England and Wales.
AB  - AIMS: To quantify the determinants of primary percutaneous coronary intervention
      (PCI) performance in England and Wales between 2004 and 2007. METHODS AND
      RESULTS: All 8653 primary PCI cases admitted to acute hospitals in England and
      Wales as recorded in the Myocardial Ischaemia National Audit Project (MINAP) 2004
      2007. We studied the impact of the volume of primary PCI cases (hospital volume)
      on door-to-balloon (DTB) times and the proportion of patients treated with
      primary PCI (hospital proportion) on 30-day mortality and employed regression
      analysis to identify reasons for DTB time variations with a multilevel component
      to express hospital variation. The proportion of patients receiving primary PCI
      increased from 5% in 2004 to 20% in 2007. Median DTB times reduced from 84 min in
      2004 to 61 min in 2007. Median DTB times decreased as the number of primary PCI
      procedures increased. The 30-day all-cause mortality rate for hospitals
      performing primary PCI on >25% of ST-elevation myocardial infarction patients
      [5.0%; 95% confidence interval (CI): 3.9-6.1%] was almost double that of
      hospitals performing primary PCI on more than 75% (2.7%; 95% CI: 2.0-3.5%). Time
      of-day, year of admission, sex, and diabetes significantly influenced DTB times.
      Hospital variation was evident by a hospital-level DTB time standard deviation of
      12 min. CONCLUSIONS: There was a large variation in DTB times between the best
      and worst performing hospitals. Although patient-related factors impacted upon
      DTB times, the volume and proportion of patients undergoing primary PCI were
      significantly associated with delay and early mortality-hospitals with the
      highest proportion of primary PCI had the lowest mortality.

PMID- 21196444
TI  - High-dose intracoronary adenosine for myocardial salvage in patients with acute
      ST-segment elevation myocardial infarction.
AB  - AIMS: Previous studies have suggested that intravenous administration of
      adenosine improves myocardial reperfusion and reduces infarct size in ST
      elevation myocardial infarction (STEMI) patients. Intracoronary administration of
      adenosine has shown conflicting results. METHODS AND RESULTS: In a prospective,
      single-centre, double-blind, placebo-controlled clinical study, we assessed
      whether selective intracoronary administration of adenosine distal to the
      occlusion site immediately before initial balloon inflation results in myocardial
      salvage and decreased microvascular obstruction (MVO) as assessed with cardiac
      magnetic resonance imaging (MRI). Using a combination of T(2)-weighted and
      contrast-enhanced sequences, myocardial salvage index (MSI) was defined as the
      percentage of the area at risk that did not become necrotic. We randomized 112
      patients presenting with STEMI within 12 h from symptom onset to selective
      intracoronary administration of adenosine 4 mg or matching placebo. In 100/110
      (91%) patients receiving study drug, MRI was performed on Days 2-3. No
      significant difference in MSI was found between adenosine- and placebo-treated
      patients: 41.3% (20.8, 66.7) vs. 47.8% (39.8, 60.9) [median (Q1, Q3)] (P = 0.52).
      The extent of MVO was comparable in both groups, with a trend favouring the
      placebo group: 2.4 g (0.0, 6.8) vs. 5.9 g (0.0, 12.8) after adenosine (P = 0.07).
      TIMI flow grade, TIMI frame count, myocardial blush grade, and ST-segment
      resolution after primary percutaneous coronary intervention were similar between
      groups. After 4 months, infarct size was similar in both treatment groups.
      CONCLUSION: We found no evidence that selective high-dose intracoronary
      administration of adenosine distal to the occlusion site of the culprit lesion in
      STEMI patients results in incremental myocardial salvage or a decrease in
      microvascular obstruction.

PMID- 21196445
TI  - Repeated and targeted transfer of angiogenic plasmids into the infarcted rat
      heart via ultrasound targeted microbubble destruction enhances cardiac repair.
AB  - AIMS: Ultrasound-targeted microbubble destruction (UTMD) uses ultrasound energy
      to selectively deliver genes into the myocardium using plasmids conjugated to
      microbubbles. We hypothesized that repeated delivery of stem cell-mobilizing
      genes could boost the ability of this therapy to enhance cardiac repair and
      ventricular function after a myocardial infarction. METHODS AND RESULTS:
      Beginning 7 days after coronary artery ligation, stem cell factor (SCF) and
      stromal cell-derived factor (SDF)-1alpha genes were administered to adult rats
      using 1, 3, or 6 UTMD treatments (repeat 1, 3, and 6 groups) at 2-day intervals
      (control=6 treatments with empty plasmid). Cardiac function (echocardiography)
      and myocardial perfusion (myocardial contrast echocardiography) were assessed on
      Days -7, 0, and 24 relative to the first treatment. Histological and biochemical
      assessments were performed on Day 24. Multiple UTMD treatments were associated
      with an increased presence of myocardial SCF and SDF-1alpha proteins and their
      receptors (vs. control and Repeat 1). All UTMD recipients exhibited increased
      vascular densities and smaller infarct regions (vs. control), with the highest
      ventricular densities in response to multiple treatments. Myocardial perfusion
      and ventricular function at Day 24 also improved progressively (vs. control) with
      the number of UTMD treatments. CONCLUSIONS: Targeted ultrasound delivery of SCF
      and SDF-1alpha genes to the infarcted myocardium recruited progenitor cells and
      increased vascular density. Multiple UTMD treatments enhanced tissue repair,
      perfusion, and cardiac function. Repeated UTMD therapy may be applied to tailor
      the number of interventions required to optimize cardiac regeneration after an
      infarction.

PMID- 21196446
TI  - Stock volatility as a risk factor for coronary heart disease death.
AB  - AIMS: The volatility of financial markets may cause substantial emotional and
      physical stress among investors. We hypothesize that this may have adverse
      effects on cardiovascular health. The Chinese stock markets were extremely
      volatile between 2006 and 2008. We, therefore, examined the relationship between
      daily change of the Shanghai Stock Exchange (SSE) Composite Index (referred as
      the Index) and coronary heart disease (CHD) deaths from 1 January 2006 to 31
      December 2008 in Shanghai, the financial capital of China. METHODS AND RESULTS:
      Daily death and stock performance data were collected from the Shanghai Center
      for Disease Control and Prevention and SSE, respectively. Data were analysed with
      over-dispersed generalized linear Poisson models, controlling for long-term and
      seasonal trends of CHD mortality, day of the week, Index closing value, weather
      conditions, and air pollution levels. We observed a U-shaped relationship between
      the Index change and CHD deaths: both rising and falling of the Index were
      associated with more deaths and the fewest deaths coincided with little or no
      change of the index. We also examined the absolute daily change of the Index in
      relation to CHD deaths: in a 1-day lag model, each 100-point change of the Index
      corresponded to 5.17% (95% confidence interval: 1.71, 8.63%) increase in CHD
      deaths. Further analysis showed that the association was stronger for out-of
      hospital CHD death than for in-hospital death. CONCLUSION: We found that CHD
      deaths fluctuated with daily stock changes in Shanghai, suggesting that stock
      volatility may adversely affect cardiovascular health.

PMID- 21196447
TI  - Crab moving sideways...

PMID- 21196448
TI  - Signal peptide replacements enhance expression and secretion of hepatitis C virus
      envelope glycoproteins.
AB  - A large number of researches focused on glycoproteins E1 and E2 of hepatitis C
      virus (HCV) aimed at the development of anti-HCV vaccines and inhibitors.
      Enhancement of E1/E2 expression and secretion is critical for the
      characterization of these glycoproteins and thus for subunit vaccine development.
      In this study, we designed and synthesized three signal peptide sequences based
      on online programs SignalP, TargetP, and PSORT, then removed and replaced the
      signal peptide preceding E1/E2 by overlapping the polymerase chain reaction
      method. We assessed the effect of this alteration on E1/E2 expression and
      secretion in mammalian cells, using western blot analysis, dot blot, and
      Galanthus nivalis agglutinin lectin capture enzyme immunoassay. Replacing the
      peptides preceding E1 and E2 with the signal peptides of the tissue plasminogen
      activator and Gaussia luciferase resulted in maximum enhancement of E1/E2
      expression and secretion of E1 in mammalian cells, without altering
      glycosylation. Such an advance would help to facilitate both the research of
      E1/E2 biology and the development of an effective HCV subunit vaccine. The
      strategy used in this study could be applied to the expression and production of
      other glycoproteins in mammalian cell line-based systems.

PMID- 21196449
TI  - Inhibition of lung cancer cell proliferation mediated by human mesenchymal stem
      cells.
AB  - Human mesenchymal stem cells (hMSCs) are mostly studied for their potential
      clinical use. Recently, much attention in the field of cancer research has been
      paid to hMSCs. In this study, we investigated the influence of hMSCs on the
      proliferation of lung cancer cell lines SK-MES-1 and A549 in vitro and in vivo by
      using a co-culture system and the hMSCs-conditioned medium. Our results
      demonstrated that hMSCs could inhibit the proliferation of SK-MES-1 and A549
      cells, and induce the apoptosis of tumor cells in vitro via some soluble factors.
      Animal study showed that these soluble factors from hMSCs could suppress
      tumorigenesis and tumor angiogenesis by treating preliminarily tumor cells with
      the hMSCs-conditioned medium. The downregulated expression of vascular
      endothelial growth factor in tumor cells might be the mechanism of interference
      in tumor angiogenesis, which was verified by western blot analysis and
      immunohistochemistry assay. Taken together, our results suggested that the hMSCs
      could inhibit tumor cell growth by secreting some soluble factors.

PMID- 21196450
TI  - Cotyledon damage affects seed number through final plant size in the annual
      grassland species Medicago lupulina.
AB  - BACKGROUND AND AIMS: The effects of cotyledon damage on seedling growth and
      survival are relatively well established, but little is known about the effects
      on aspects of plant fitness such as seed number and size. Here the direct and
      indirect mechanisms linking cotyledon damage and plant fitness in the annual
      species Medicago lupulina are examined. METHODS: Growth and reproductive traits,
      including mature plant size, time to first flowering, flower number, seed number
      and individual seed mass were monitored in M. lupulina plants when zero, one or
      two cotyledons were removed at 7 d old. Structural equation modelling (SEM) was
      used to examine the mechanisms linking cotyledon damage to seed number and seed
      mass. KEY RESULTS: Cotyledon damage reduced seed number but not individual seed
      mass. The primary mechanism was a reduction in plant biomass with cotyledon
      damage that in turn reduced seed number primarily through a reduction in flower
      numbers. Although cotyledon damage delayed flower initiation, it had little
      effect on seed number. Individual seed mass was not affected by cotyledon
      removal, but there was a trade-off between seed number and seed mass.
      CONCLUSIONS: It is shown how a network of indirect mechanisms link damage to
      cotyledons and fitness in M. lupulina. Cotyledon damage had strong direct effects
      on both plant size and flowering phenology, but an analysis of the causal
      relationships among plant traits and fitness components showed that a reduction
      in plant size associated with cotyledon damage was an important mechanism
      influencing fitness.

PMID- 21196451
TI  - One-year outcomes and a cost-effectiveness analysis for smokers accessing group
      based and pharmacy-led cessation services.
AB  - INTRODUCTION: An observational study examining 1-year follow-up of clients of two
      National Health Service smoking cessation services in Glasgow was used to inform
      a cost-effectiveness analysis. One service involved 7 weeks of group-based
      support (n = 411) and the other consisted of up to 12 weeks of one-to-one
      counseling with pharmacists (n = 1,374). Pharmacological aids to quitting (e.g.,
      nicotine replacement therapy) were available to all clients. METHODS: Quit rates
      were calculated for each service at 52 weeks after the quit date, and these were
      used for an economic evaluation of both the annual and the lifetime cost
      effectiveness of the pharmacy- and group-based interventions in comparison with a
      baseline "self-quit" scenario. The annual cost-effectiveness model established
      the incremental cost per 52-week quitter, while a Markov model was developed for
      the lifetime analysis to estimate the potential lifetime outcomes in terms of
      cost per quality-adjusted life years (QALY) gained, to account for the benefits
      quitters will receive in terms of extended life years and improvements in quality
      of life from smoking cessation. RESULTS: The proportion of carbon monoxide
      validated quitters from both services combined fell from 22.5% at 4-week follow
      up to 3.6% at 52 weeks. The group service achieved a higher quit rate (6.3%) than
      the pharmacy service (2.8%) but was more intensive and required greater overhead
      costs. The lifetime analysis resulted in an incremental cost per QALY of L4,800
      for the group support and L2,600 for pharmacy one-to-one counseling. CONCLUSIONS:
      Despite disappointing 1-year quit rates, both services were considered to be
      highly cost-effective.

PMID- 21196452
TI  - Editorial. 40th Anniversary of the Japanese Journal of Clinical Oncology (JJCO).

PMID- 21196453
TI  - The benchmark analysis of gastric, colorectal and rectal cancer pathways: toward
      establishing standardized clinical pathway in the cancer care.
AB  - Most clinical pathways in treating cancers in Japan are based on individual
      physician's personal experiences rather than on an empirical analysis of clinical
      data such as benchmark comparison with other hospitals. Therefore, these pathways
      are far from being standardized. By comparing detailed clinical data from five
      cancer centers, we have observed various differences among hospitals. By
      conducting benchmark analyses, providing detailed feedback to the participating
      hospitals and by repeating the benchmark a year later, we strive to develop more
      standardized clinical pathways for the treatment of cancers. The Cancer Quality
      Initiative was launched in 2007 by five cancer centers. Using diagnosis procedure
      combination data, the member hospitals benchmarked their pre-operative and post
      operative length of stays, the duration of antibiotics administrations and the
      post-operative fasting duration for gastric, colon and rectal cancers. The
      benchmark was conducted by disclosing hospital identities and performed using
      2007 and 2008 data. In the 2007 benchmark, substantial differences were shown
      among five hospitals in the treatment of gastric, colon and rectal cancers. After
      providing the 2007 results to the participating hospitals and organizing several
      brainstorming discussions, significant improvements were observed in the 2008
      data study. The benchmark analysis of clinical data is extremely useful in
      promoting more standardized care and, thus in improving the quality of cancer
      treatment in Japan. By repeating the benchmark analyses, we can offer truly
      clinical evidence-based higher quality standardized cancer treatment to our
      patients.

PMID- 21196454
TI  - A case of rapidly growing esophageal cancer with tracheo-esophageal fistula.

PMID- 21196455
TI  - Comparison of time trends in non-Hodgkin's lymphoma mortality (1990-2006) between
      countries based on the WHO mortality database.

PMID- 21196456
TI  - Beryllium metal II. a review of the available toxicity data.
AB  - Beryllium metal was classified in Europe collectively with beryllium compounds,
      e.g. soluble salts. Toxicological equivalence was assumed despite greatly
      differing physicochemical properties. Following introduction of the Registration,
      Evaluation, Authorization and Restriction of Chemicals (REACH) regulation,
      beryllium metal was classified as individual substance and more investigational
      efforts to appropriately characterize beryllium metal as a specific substance
      apart from soluble beryllium compounds was required. A literature search on
      toxicity of beryllium metal was conducted, and the resulting literature compiled
      together with the results of a recently performed study package into a
      comprehensive data set. Testing performed under Organisation for Economic Co
      Operation and Development guidelines and Good Laboratory Practice concluded that
      beryllium metal was neither a skin irritant, an eye irritant, a skin sensitizer
      nor evoked any clinical signs of acute oral toxicity; discrepancies between the
      current legal classification of beryllium metal in the European Union (EU) and
      the experimental results were identified. Furthermore, genotoxicity and
      carcinogenicity were discussed in the context of the literature data and the new
      experimental data. It was concluded that beryllium metal is unlikely to be a
      classical nonthreshold mutagen. Effects on DNA repair and morphological cell
      transformation were observed but need further investigation to evaluate their
      relevance in vivo. Animal carcinogenicity studies deliver evidence of
      carcinogenicity in the rat; however, lung overload may be a species-specific
      confounding factor in the existing studies, and studies in other species do not
      give convincing evidence of carcinogenicity. Epidemiology has been intensively
      discussed over the last years and has the problem that the studies base on the
      same US beryllium production population and do not distinguish between metal and
      soluble compounds. It is noted that the correlation between beryllium exposure
      and carcinogenicity, even including the soluble compounds, remains under
      discussion in the scientific community and active research is continuing.

PMID- 21196457
TI  - Beryllium metal I. experimental results on acute oral toxicity, local skin and
      eye effects, and genotoxicity.
AB  - The toxicity of soluble metal compounds is often different from that of the
      parent metal. Since no reliable data on acute toxicity, local effects, and
      mutagenicity of beryllium metal have ever been generated, beryllium metal powder
      was tested according to the respective Organisation for Economical Co-Operation
      and Development (OECD) guidelines. Acute oral toxicity of beryllium metal was
      investigated in rats and local effects on skin and eye in rabbits. Skin
      sensitizing properties were investigated in guinea pigs (maximization method).
      Basic knowledge about systemic bioavailability is important for the design of
      genotoxicity tests on poorly soluble substances. Therefore, it was necessary to
      experimentally compare the capacities of beryllium chloride and beryllium metal
      to form ions under simulated human lung conditions. Solubility of beryllium metal
      in artificial lung fluid was low, while solubility in artificial lysosomal fluid
      was moderate. Beryllium chloride dissolution kinetics were largely different, and
      thus, metal extracts were used in the in vitro genotoxicity tests. Genotoxicity
      was investigated in vitro in a bacterial reverse mutagenicity assay, a mammalian
      cell gene mutation assay, a mammalian cell chromosome aberration assay, and an
      unscheduled DNA synthesis (UDS) assay. In addition, cell transformation was
      tested in a Syrian hamster embryo cell assay, and potential inhibition of DNA
      repair was tested by modification of the UDS assay. Beryllium metal was found not
      to be mutagenic or clastogenic based on the experimental in vitro results.
      Furthermore, treatment with beryllium metal extracts did not induce DNA repair
      synthesis, indicative of no DNA-damaging potential of beryllium metal. A cell
      transforming potential and a tendency to inhibit DNA repair when the cell is
      severely damaged by an external stimulus were observed. Beryllium metal was also
      found not to be a skin or eye irritant, not to be a skin sensitizer, and not to
      have relevant acute oral toxic properties.

PMID- 21196458
TI  - Results of the EURADOS extremity dosemeter intercomparison 2009.
AB  - This paper presents the results of an intercomparison for extremity dosemeters
      organised by the European radiation dosimetry group in 2009. In total, 59 systems
      were tested during this exercise including ring, stall and wrist dosemeters. A
      total of 1652 dosemeters were irradiated in the selected fields of photons and
      beta radiation qualities on appropriate phantoms (ISO finger and pillar phantom)
      in the dose quantity H(p)(0.07). All irradiations were carried out in selected
      accredited reference dosemetry laboratories (Seibersdorf Laboratories, Austria
      and IRSN, France). The results show that, especially at low-energy beta
      radiations ((85)Kr) and for beta irradiations with large angles of incidence (60
      degrees ), many tested systems show pronounced under responses. On the other
      hand, for photon irradiations down to energies of 16 keV most systems showed good
      results. A participants meeting was held at IM2010 with discussion on both
      general aspects of this intercomparison and specific problems.

PMID- 21196459
TI  - A cell kinetic model of granulopoiesis under radiation exposure: extension from
      rodents to canines and humans.
AB  - As significant ionising radiation exposure will occur during prolonged space
      travel in future, it is essential to understand their adverse effects on the
      radiosensitive organ systems that are important for immediate survival of humans,
      e.g. the haematopoietic system. In this paper, a biomathematical model of
      granulopoiesis is used to analyse the granulocyte changes seen in the blood of
      mammalians under acute and continuous radiation exposure. This is one of a set of
      haematopoietic models that have been successfully utilised to simulate and
      interpret the experimental data of acute and chronic radiation on rodents.
      Extension to canine and human systems indicates that the results of the model are
      consistent with the cumulative experimental and empirical data from various
      sources, implying the potential to integrate them into one united model system to
      monitor the haematopoietic response of various species under irradiation. The
      suppression of granulocytes' level of a space traveller under chronic stress of
      low-dose irradiation as well as the granulopoietic response when encountering a
      historically large solar particle event is also discussed.

PMID- 21196460
TI  - Validation of efficiency tracing and zero detection threshold techniques using
      liquid scintillation analyser TriCarb.
AB  - Efficiency tracing with unquenched 14C and zero detection threshold with
      unquenched 3H as tracers are practical and simple techniques which have been
      implemented to quantify the activity of various beta emitters using liquid
      scintillation analyser. These techniques are used to study the influence of
      quench level on activity quantification and the activity levels up to which these
      techniques are applicable. The results indicate that, for an activity level of
      166.67 Bq, both the techniques are in good agreement with the reference activity
      with a relative discrepancy of <=4.6 %. The relative discrepancy of ~10 % is
      observed for extreme quench values of ~111. For all the radionuclides with the
      activity level of 1.67 Bq, the uncertainty in activity quantification raises to
      ~8 % and for the activity level from 8.33 to 100 Bq, the uncertainty reduces to 1
      %.

PMID- 21196461
TI  - A model for analysis of the yield and the level of clustering of radiation
      induced DNA-strand breaks in hydrated plasmids.
AB  - Although it is widely accepted that the spatial distribution of strand breaks is
      highly relevant to the biological consequences of radiation, the extent to which
      strand breaks are clustered is not usually demonstrated directly from the
      experimental data. To evaluate the spatial distribution of radiation-induced
      strand breaks, the authors have developed a model for the generation of strand
      breaks after irradiation. The model assumes that (1) a radiation track has a
      certain probability of 'hitting' a plasmid, (2) the radiation generates strand
      break(s) by chance within a relatively small region that could produce double
      strand breaks and (3) the number of strand breaks generated within the region
      follows a Poisson distribution. To find out whether the model is valid, the
      authors compared the calculated values with the experimental data obtained by a
      plasmid DNA assay. Taking into account the inherent bias of the plasmid assay,
      the model described well the experimental results of hydrated plasmids exposed to
      radiation.

PMID- 21196462
TI  - A new nano-enhanced technology proposed to quantify intracellular detection of
      radiation-induced metabolic processes.
AB  - A new approach to intracellular detection and imaging of metabolic processes and
      pathways is presented that uses surface plasmon resonance to enhance interactions
      between photon-absorbing metabolites and metal nanoparticles in contact with
      cells in vitro or in vivo. Photon absorption in the nanoparticles creates plasmon
      fields, enhancing intrinsic metabolite fluorescence, thereby increasing
      absorption and emission rates, creating new spectral emission bands, shortening
      fluorescence lifetimes, becoming more photo-stable and increasing fluorescent
      resonance energy transfer efficiency. Because the cells remain viable, it is
      proposed that the method may be used to interrogate cells prior to and after
      irradiation, with the potential for automated analyses of intracellular
      interactive pathways associated with radiation exposures at lower doses than
      existing technologies. The design and concepts of the instrument are presented
      along with data for unexposed cells.

PMID- 21196463
TI  - Feasibility study on using imaging plates to estimate thermal neutron fluence in
      neutron-gamma mixed fields.
AB  - In current radiotherapy, neutrons are produced in a photonuclear reaction when
      incident photon energy is higher than the threshold. In the present study, a
      method of discriminating the neutron component was investigated using an imaging
      plate (IP) in the neutron-gamma-ray mixed field. Two types of IP were used: a
      conventional IP for beta- and gamma rays, and an IP doped with Gd for detecting
      neutrons. IPs were irradiated in the mixed field, and the photo-stimulated
      luminescence (PSL) intensity of the thermal neutron component was discriminated
      using an expression proposed herein. The PSL intensity of the thermal neutron
      component was proportional to thermal neutron fluence. When additional
      irradiation of photons was added to constant neutron irradiation, the PSL
      intensity of the thermal neutron component was not affected. The uncertainty of
      PSL intensities was approximately 11.4 %. This method provides a simple and
      effective means of discriminating the neutron component in a mixed field.

PMID- 21196464
TI  - The use of active personal dosemeters as a personal monitoring device: comparison
      with TL dosimetry.
AB  - The use of active personal dosemeters (APDs) not only as a warning device but
      also, in some cases, as an official and hence stand-alone dosemeter is rapidly
      increasing. A comparison in terms of dose, energy and angle dependence, among
      different types of APD and a routinely used whole-body thermoluminescence
      dosemeter (TLD) has been performed. Significant differences were found between
      the TLD readings and mainly some not commonly used APDs. The importance of
      choosing the best adapted APD according to the radiation field characteristics is
      pointed out.

PMID- 21196465
TI  - Modelling the way Ku binds DNA.
AB  - Ku plays a crucial role in the non-homologous end joining pathway to repair DNA
      double-strand breaks. In this study, we modelled the full-length Ku heterodimer
      from the truncated crystal structure and NMR structure, and conducted a series of
      docking and molecular dynamics simulations in an effort to probe the structural,
      dynamical and energetic features of each domain in free Ku and Ku-DNA complexes.

PMID- 21196466
TI  - Visualisation and quantification of lung content of radionuclides associated with
      nuclear and radiological emergencies.
AB  - In a situation when radionuclides accidentally or deliberately are dispersed in
      the environment, there is a need for rapid investigation of the internal
      contamination in exposed individuals. In this work, the possibilities of
      visualising and quantifying uptakes of different radionuclides in the lung region
      of an adult individual using gamma camera systems have been examined, mainly on a
      two-headed stationary clinical gamma camera. An anthropomorphic phantom was used
      to mimic acute lung uptakes in three different body sizes. The gamma camera was
      calibrated with the lung inserts filled with a homogeneous solution of 99Tc(m),
      46Sc and 32P, or with point sources of 241Am, 57Co, 85Sr, 137Cs and 90Sr/90Y. It
      was found that for the stationary gamma camera the minimum detectable activity in
      the lungs using a 5-min acquisition time ranged from 0.53 kBq for 46Sc to 50 kBq
      for 32P. Furthermore, the point sources of 137Cs, 60Co and 90Sr/90Y (0.16, 0.80
      and 2.2 MBq, respectively) located in the lung insert of the phantom, could be
      clearly visualised, exhibiting distinct intensity maxima. It is thus concluded
      that gamma camera systems can be useful for rapid assessment of acute intakes of
      radionuclides associated with emergency preparedness, both in terms of
      localisation and quantification.

PMID- 21196467
TI  - Ventricular oversensing in an implantable defibrillator during lead impedance
      testing.

PMID- 21196468
TI  - Nephrinuria associates with multiple renal traits in type 2 diabetes.
AB  - BACKGROUND: The involvement of nephrin in controlling renal function is unclear
      with the literature only emphasizing its role in albuminuria. We therefore
      investigated the potential association between nephrinuria as evidenced by the
      appearance of urinary immunopositive nephrin fragments, with multiple renal
      traits. METHODS: Western blot analysis of the urine samples from a cross
      sectional study of 381 Chinese type 2 diabetic patients revealed four distinct
      protein fragments, indicative of nephrinuria. Albuminuria was measured in random
      spot urine samples using the albumin/creatinine ratio (ACR), while estimated
      glomerular filtration rate (eGFR) was calculated using the creatinine-based
      Modification of Diet in Renal Disease formula. RESULTS: Each nephrin fragment was
      associated with a decline in eGFR (smallest P = 0.001). Even with the inclusion
      of logarithmic form of ACR (ln ACR) in the multivariate model, nephrinuria still
      remained significantly associated with lower eGFR (smallest P < 0.05).
      Nephrinuria was also strongly associated with lnACR and this finding was
      independent of eGFR (smallest P < 0.001). Thus, nephrinuria was independently
      associated with both renal traits in the form of lnACR and eGFR. Furthermore,
      nephrinuria was significantly associated with lower eGFR even among
      normoalbuminuric patients (ACR <= 30 mg/g) (smallest P = 0.002), potentially
      implicating nephrinuria in the development of normoalbuminuric renal
      insufficiency. Apart from the renal traits under investigation, the presence of
      nephrinuria did not associate with other patient clinical characteristics.
      CONCLUSIONS: Nephrinuria was associated with multiple renal traits in type 2
      diabetes even in normoalbuminuric patients who are traditionally perceived as
      having a low risk of chronic kidney disease.

PMID- 21196469
TI  - ESAT-6 secretion-independent impact of ESX-1 genes espF and espG1 on virulence of
      Mycobacterium tuberculosis.
AB  - BACKGROUND: The pathogenesis of Mycobacterium tuberculosis largely depends on the
      secretion of the 6-kD early secreted antigenic target ESAT-6 (EsxA) and the 10-kD
      culture filtrate protein CFP-10 (EsxB) via the ESX-1/typeVII secretion system.
      Although gene products from the core RD1 region have been shown to be deeply
      implicated in this process, less is known about proteins encoded further upstream
      in the 5' region of the ESX-1 cluster, such as the ESX-1 secretion-associated
      proteins (Esps) EspF or EspG(1). METHODS: To elucidate the role of EspF/G(1),
      whose orthologs in Mycobacterium marinum and Mycobacterium smegmatis are
      reportedly involved in EsxA/B secretion, we constructed 3 M. tuberculosis
      knockout strains deleted for espF, espG(1) or the segment corresponding to the
      combined RD1(bcg)-RD1(mic) region of bacille Calmette-Guerin (BCG) and
      Mycobacterium microti, which also contains espF and espG(1). RESULTS: Analysis of
      these strains revealed that, unlike observations with the model organisms M.
      smegmatis or M. marinum, disruption of espF and espG(1) in M. tuberculosis did
      not impact the secretion and T cell recognition of EsxA/B but still caused severe
      attenuation. CONCLUSIONS: The separation of the 2 ESX-1-connected phenotypes (ie,
      EsxA/B secretion and virulence) indicates that EsxA/B secretion is not the only
      readout for a functional ESX-1 system and suggests that other processes involving
      EspF/G(1) also play important roles in ESX-1-mediated pathogenicity.

PMID- 21196470
TI  - Molecular evolution of the ligands of the insulin-signaling pathway: dilp genes
      in the genus Drosophila.
AB  - Drosophila melanogaster, unlike mammals, has seven insulin-like peptides (DILPS).
      In Drosophila, all seven genes (dilp1-7) are single copy in the 12 species
      studied, except for D. grimshawi with two tandem copies of dilp2. Our comparative
      analysis revealed that genes dilp1-dilp7 exhibit differential functional
      constraint, which is indicative of some functional divergence. Species of the
      subgenera Sophophora and Drosophila differ in some traits likely affected by the
      insulin-signaling pathway, such as adult body size. It is in the branch
      connecting the two subgenera that we found the footprint left by positive
      selection driving nonsynonymous changes at some dilp1 codons to fixation.
      Finally, the similar rate at which the two dilp2 copies of D. grimshawi have
      evolved since their duplication and the presence of a putative regulatory region
      highly conserved between the two paralogs would suggest that both copies were
      preserved either because of subfunctionalization or dose dependency rather than
      by the neofunctionalization of one of the two copies.

PMID- 21196471
TI  - The subjective utility of early psychosocial interventions following combat
      deployment.
AB  - BACKGROUND: Third Location Decompression (TLD) is the process through which
      personnel, returning from combat operations, begin to psychologically 'unwind'.
      Decompression comprises welfare activities, such as contacting home, beach
      events, social events, psycho-educational briefings and controlled re
      introduction to alcohol. AIMS: To assess the subjective utility of decompression
      by surveying all British troops transiting the TLD facility in Cyprus, during
      2008. METHODS: Analysis of distributed surveys completed by personnel who had
      deployed either to Iraq or Afghanistan. The main outcome was the subjective
      utility of the decompression process, with operational exposures, stigma, early
      post-traumatic stress (PTS) symptoms and adjustment concerns also measured.
      RESULTS: Response rate was 87% (11,304 returned surveys). Eighty per cent of
      respondents reported being ambivalent or not wanting to go through TLD before
      decompression; however, on completion, 91% reported finding it useful. The desire
      to participate was the strongest predictor of perceived helpfulness. Troops who
      found the TLD less helpful included those who had been through the process
      before, combat troops and non-commissioned officers. Twelve per cent reported
      substantial concerns about re-establishing relationships or settling down to
      'normal life'; those reporting more adjustment concerns were more likely to
      perceive TLD as helpful. Six per cent reported significant PTS symptoms and 27%
      of troops reported substantial levels of stigma related to mental health and
      barriers to care. CONCLUSIONS: TLD was well received by troops following combat
      deployment. However, TLD does not appear to be equally acceptable to all and
      alterations to the TLD programme for certain subgroups might be required.

PMID- 21196472
TI  - Vasospasm in the feet in workers assessed for HAVS.
AB  - BACKGROUND: Previous studies have suggested that the presence of the vascular
      component of hand-arm vibration syndrome (HAVS) in the hands increases the risk
      of cold-induced vasospasm in the feet. AIMS: To determine if objectively measured
      cold-induced vasospasm in the hands is a risk factor for objectively measured
      cold-induced vasospasm in the feet in workers being assessed for HAVS. METHODS:
      The subjects were 191 male construction workers who had a standardized assessment
      for HAVS including cold provocation digital photocell plethysmography of the
      hands and feet to measure cold-induced vasospasm. Bivariate analysis and
      multinomial logistic regression were used to examine the association between
      plethysmographic findings in the feet and predictor variables including years
      worked in construction, occupation, current smoking, cold intolerance in the
      feet, the Stockholm vascular stage and plethysmographic findings in the hands.
      RESULTS: Sixty-one (32%) subjects had non-severe vasospasm and 59 (31%) had
      severe vasospasm in the right foot with the corresponding values being 57(30%)
      and 62 (32%) in the left foot. Multinomial logistic regression indicated that the
      only statistically significant predictor of severe vasospasm in the feet was the
      presence of severe vasospasm in the hands (OR: 4.11, 95% CI: 1.60-10.6, P < 0.01
      on the right side and OR: 4.97, 95% CI: 1.82-13.53, P < 0.01 on the left side).
      Multinomial logistic regression analysis did not indicate any statistically
      significant predictors of non-severe vasospasm in the feet. CONCLUSIONS: Workers
      assessed for HAVS frequently have cold-induced vasospasm of their feet. The main
      predictor of severe vasospastic foot abnormalities is severe cold-induced
      vasospasm in the hands.

PMID- 21196473
TI  - Towards a better understanding of the generation of fructan structure diversity
      in plants: molecular and functional characterization of a sucrose:fructan 6
      fructosyltransferase (6-SFT) cDNA from perennial ryegrass (Lolium perenne).
AB  - The main storage compounds in Lolium perenne are fructans with prevailing beta(2
      6) linkages. A cDNA library of L. perenne was screened using Poa secunda
      sucrose:fructan 6-fructosyltransferase (6-SFT) as a probe. A full-length Lp6-SFT
      clone was isolated as shown by heterologous expression in Pichia pastoris. High
      levels of Lp6-SFT transcription were found in the growth zone of elongating
      leaves and in mature leaf sheaths where fructans are synthesized. Upon fructan
      synthesis induction, Lp6-SFT transcription was high in mature leaf blades but
      with no concomitant accumulation of fructans. In vitro studies with the
      recombinant Lp6-SFT protein showed that both 1-kestotriose and 6G-kestotriose
      acted as fructosyl acceptors, producing 1- and 6-kestotetraose (bifurcose) and
      6G,6-kestotetraose, respectively. Interestingly, bifurcose formation ceased and
      6G,6-kestotetraose was formed instead, when recombinant fructan:fructan 6G
      fructosyltransferase (6G-FFT) of L. perenne was introduced in the enzyme assay
      with sucrose and 1-kestotriose as substrates. The remarkable absence of bifurcose
      in L. perenne tissues might be explained by a higher affinity of 6G-FFT, as
      compared with 6-SFT, for 1-kestotriose, which is the first fructan formed.
      Surprisingly, recombinant 6-SFT from Hordeum vulgare, a plant devoid of fructans
      with internal glucosyl residues, also produced 6G,6-kestotetraose from sucrose
      and 6G-kestotriose. In the presence of recombinant L. perenne 6G-FFT, it produced
      6G,6-kestotetraose from 1-kestotriose and sucrose, like L. perenne 6-SFT. Thus,
      we demonstrate that the two 6-SFTs have close catalytic properties and that the
      distinct fructans formed in L. perenne and H. vulgare can be explained by the
      presence of 6G-FFT activity in L. perenne and its absence in H. vulgare.

PMID- 21196475
TI  - Hormonal control of nitrogen acquisition: roles of auxin, abscisic acid, and
      cytokinin.
AB  - Nitrogen is the mineral nutrient that often limits plant growth and development.
      In response to changes in nitrogen supply, plants display elaborate responses at
      both physiological and morphological levels to adjust their growth and
      development. Because higher plants consist of multiple organs with different
      functions and nutritional requirements, they rely on local and long-distance
      signalling pathways to coordinate the responses at the whole-plant level.
      Phytohormones have been considered as signalling substances of such pathways.
      Amongst phytohormones, abscisic acid, auxin, and cytokinins have been closely
      linked to nitrogen signalling. Recent evidence has provided some insights into
      how nitrogen and the phytohormone signals are integrated to bring about changes
      in physiology and morphology. In this review, the evidence is summarized, mostly
      focusing on examples related to nitrogen acquisition.

PMID- 21196474
TI  - Immunodetection of retinoblastoma-related protein and its phosphorylated form in
      interphase and mitotic alfalfa cells.
AB  - Plant retinoblastoma-related (RBR) proteins are primarily considered as key
      regulators of G(1)/S phase transition, with functional roles in a variety of
      cellular events during plant growth and organ development. Polyclonal antibody
      against the C-terminal region of the Arabidopsis RBR1 protein also specifically
      recognizes the alfalfa 115 kDa MsRBR protein, as shown by the antigen competition
      assay. The MsRBR protein was detected in all cell cycle phases, with a moderate
      increase in samples representing G(2)/M cells. Antibody against the human phospho
      pRb peptide (Ser807/811) cross-reacted with the same 115 kDa MsRBR protein and
      with the in vitro phosphorylated MsRBR protein C-terminal fragment. Phospho-MsRBR
      protein was low in G(1) cells. Its amount increased upon entry into the S phase
      and remained high during the G(2)/M phases. Roscovitine treatment abolished the
      activity of alfalfa MsCDKA1;1 and MsCDKB2;1, and the phospho-MsRBR protein level
      was significantly decreased in the treated cells. Colchicine block increased the
      detected levels of both forms of MsRBR protein. Reduced levels of the MsRBR
      protein in cells at stationary phase or grown in hormone-free medium can be a
      sign of the division-dependent presence of plant RBR proteins. Immunolocalization
      of the phospho-MsRBR protein indicated spots of variable number and size in the
      labelled interphase nuclei and high signal intensity of nuclear granules in
      prophase. Structures similar to phospho-MsRBR proteins cannot be recognized in
      later mitotic phases. Based on the presented western blot and immunolocalization
      data, the possible involvement of RBR proteins in G(2)/M phase regulation in
      plant cells is discussed.

PMID- 21196476
TI  - Circadian regulation of chloroplastic f and m thioredoxins through control of the
      CCA1 transcription factor.
AB  - Chloroplastic thioredoxins f and m (TRX f and TRX m) mediate light regulation of
      carbon metabolism through the activation of Calvin cycle enzymes. The role of TRX
      f and m in the activation of Calvin cycle enzymes is best known among the TRX
      family. However, the discoveries of new potential targets extend the functions of
      chloroplastic TRXs to other processes in non-photosynthetic tissues. As occurs
      with numerous chloroplast proteins, their expression comes under light
      regulation. Here, the focus is on the light regulation of TRX f and TRX m in pea
      and Arabidopsis during the day/night cycle that is maintained during the
      subjective night. In pea (Pisum sativum), TRX f and TRX m1 expression is shown to
      be governed by a circadian oscillation exerted at both the transcriptional and
      protein levels. Binding shift assays indicate that this control probably involves
      the interaction of the CCA1 transcription factor and an evening element (EE)
      located in the PsTRX f and PsTRX m1 promoters. In Arabidopsis, among the
      multigene family of TRX f and TRX m, AtTRX f2 and AtTRX m2 mRNA showed similar
      circadian oscillatory regulation, suggesting that such regulation is conserved in
      plants. However, this oscillation was disrupted in plants overexpressing CCA1
      (cca1-ox) or repressing CCA1 and LHY (cca1-lhy). The physiological role of the
      oscillatory regulation of chloroplastic TRX f and TRX m in plants during the
      day/night cycle is discussed.

PMID- 21196478
TI  - The effect of intimate partner violence and other forms of violence against women
      on health.
AB  - BACKGROUND: There are many studies concerning the health consequences of intimate
      partner violence (IPV). However, little research has been done on the health
      consequences of other forms of violence against women (VAW) such as the violence
      perpetrated by male relatives, friends or strangers. The aims of this paper were:
      (i) to analyze the prevalence of different forms of VAW perpetrated by males at
      home, workplace and other social environments in Spain and (ii) to analyze
      whether IPV and other forms of VAW have a different or similar negative impact on
      women's health. METHODS: A sample of 13 094 women interviewed in the Spanish
      National Health Survey 2006 was included. Outcomes were physical and mental
      health indicators. Predictor variables were IPV and other VAW forms. Logistic
      regression models were fitted. RESULTS: The likelihood of coronary heart disease
      [OR: 5.28 (1.45-19.25)], chronic neck [OR: 2.01 (1.35-2.97)] and back pain [OR:
      2.34 (1.53-3.57)] was higher among women who reported IPV than among those who
      did not. Similar associations were found in the case of women affected by other
      forms of VAW. Mental health problems, with the exception of psychotropic drug
      use, were more frequent and more strongly associated with IPV than with other
      forms of VAW. CONCLUSION: There are health inequities between battered and non
      battered women, which may be related to exposure to not only IPV but also other
      forms of VAW.

PMID- 21196479
TI  - The rocky road to solar power: fiction and fact.

PMID- 21196477
TI  - Tolerance to oxidative stress induced by desiccation in Porphyra columbina
      (Bangiales, Rhodophyta).
AB  - Unravelling the mechanisms underlying desiccation tolerance is crucial in order
      to understand the position of algal species in the intertidal zone. The alga
      Porphyra columbina lives in the uppermost part of the rocky intertidal zones
      around the world and was selected as a model for this study. Naturally desiccated
      plants were collected during low tide and studied for morphological changes,
      oxidative burst induction, biomolecule oxidation, antioxidant responses, and
      photosynthetic status. Naturally hydrated plants collected during high tides were
      used for comparative purposes. In addition, changes induced by desiccation were
      assessed in vitro and the capacity to recover from desiccation was determined by
      rehydrating the fronds in seawater. The global results show that desiccation
      induces morphological and cellular alterations accompanied by a loss of ~96% of
      the water content. Overproduction of reactive oxygen species (ROS) was induced by
      desiccation and two peaks of H(2)O(2) were detected at 1 and 3 h of desiccation.
      However, during in vitro rehydration post-desiccation, the ROS quickly returned
      to the basal levels. At the biomolecular level, only a low production of oxidized
      proteins was recorded during desiccation, whereas the activity of diverse
      antioxidant enzymes increased. However, this activity diminished to near basal
      levels during rehydration. The photosynthetic efficiency (F(v)/F(m)) during
      desiccation declined by 94-96% of the values recorded in hydrated plants. This
      reduction was generated by the low levels of trapped energy flux per cross
      section (TRo/CS), electron transport flux per CS (ETo/CS), and density of
      reaction centres (RC/SCo) as well as the chlorophyll content. The inverse pattern
      was observed for the levels of phycocyanin and phycoerythrin content. F(v)/F(m)
      and the photosynthetic indicators were restored to normal levels after only 5 min
      of rehydration. The results indicate that desiccation in P. columbina causes
      overproduction of ROS that is efficiently attenuated. The morphological and
      photosynthetic changes could be operating as tolerance mechanisms due to the fact
      that these responses principally prevent biomolecular alteration and cellular
      collapse. Thus, the activation of different physiological mechanisms helps to
      explain the high tolerance to desiccation of P. columbina and, at least in part,
      the position of this species at the highest level in the intertidal zone.

PMID- 21196481
TI  - More than 700 people need critical care treatment as flu cases surge.

PMID- 21196483
TI  - Rheumatoid arthritis.

PMID- 21196484
TI  - Is estimating lifetime cardiovascular risk useful?

PMID- 21196485
TI  - Treating inflammatory arthritis early.

PMID- 21196488
TI  - CO2-dependent methicillin-resistant Staphylococcus aureus.

PMID- 21196489
TI  - Comparison of phenotypic and genotypic tropism determination in triple-class
      experienced HIV patients eligible for maraviroc treatment.
AB  - BACKGROUND: Determination of HIV-1 tropism is a pre-requisite to the use of CCR5
      antagonists. This study evaluated the potential of population genotypic tropism
      tests (GTTs) in clinical practice, and the correlation with phenotypic tropism
      tests (PTTs) in patients accessing routine HIV care. METHODS: Forty-nine
      consecutive plasma samples for which an original Trofile(TM) assay was performed
      were obtained from triple-class-experienced patients in need of a therapy change.
      Viral tropism was defined as the consensus of three or more tropism calls
      obtained from the combination of two independent population PTT assays (Trofile
      Biosciences, San Francisco, CA, USA, and Virco, Beerse, Belgium), population GTTs
      and GTTs based on ultra-deep sequencing. If no consensus was reached, a clonal
      PTT was performed in order to finalize the tropism call. This two-step approach
      allowed the definition of a reference tropism call. RESULTS: According to the
      reference tropism result, 35/49 samples were CCR5 tropic (R5) (patients eligible
      for maraviroc treatment) and 14/49 were assigned as non-R5 tropic. The non-R5
      samples [patients not eligible for maraviroc treatment according to the
      FDA/European Medicines Agency (EMEA) label] group included both the CXCR4 (X4)
      samples and the dual and mixed CCR5/CXCR4 (R5/X4) samples. Compared with
      Trofile(TM) population PTTs, population GTTs showed a higher sensitivity (97%)
      and a higher negative predictive value (91%), but almost equal specificity and an
      equal positive predictive value. CONCLUSIONS: In line with recent reports from
      clinical trial data, our data support the use of population genotypic tropism
      testing as a tool for tropism determination before the start of maraviroc.

PMID- 21196490
TI  - NOTCH, a new signaling pathway implicated in holoprosencephaly.
AB  - Genetics of Holoprosencephaly (HPE), a congenital malformation of the developing
      human forebrain, is due to multiple genetic defects. Most genes that have been
      implicated in HPE belong to the sonic hedgehog signaling pathway. Here we
      describe a new candidate gene isolated from array comparative genomic
      hybridization redundant 6qter deletions, DELTA Like 1 (DLL1), which is a ligand
      of NOTCH. We show that DLL1 is co-expressed in the developing chick forebrain
      with Fgf8. By treating chick embryos with a pharmacological inhibitor, we
      demonstrate that DLL1 interacts with FGF signaling pathway. Moreover, a mutation
      analysis of DLL1 in HPE patients revealed a three-nucleotide deletion. These
      various findings implicate DLL1 in early patterning of the forebrain and identify
      NOTCH as a new signaling pathway involved in HPE.

PMID- 21196492
TI  - Genome-wide association study for C-reactive protein levels identified
      pleiotropic associations in the IL6 locus.
AB  - C-reactive protein (CRP) is a hallmark acute-phase reactant and is widely used as
      a blood marker for inflammation. Substantial roles of serum CRP levels in the
      pathogenesis of diseases have been suggested, and investigation of the mechanisms
      that regulate serum CRP levels would have a substantial clinical impact. Here,
      through genome-wide association and replication studies performed using 12 854
      Japanese subjects, we identified a significant association between serum CRP
      levels and a single nucleotide polymorphism in the promoter region of interleukin
      6 (IL6) (rs2097677, P = 4.1 * 10(-11)), a typical pleiotropic pro-inflammatory
      cytokine. Our study also replicated the associations in the CRP (rs3093059, P =
      3.5 * 10(-21)) and HNF1A loci (rs7310409, P = 2.7 * 10(-8)). Pleiotropic
      association analysis with hematological and biochemical traits using 30 466
      Japanese subjects demonstrated that the CRP-increasing allele of rs2097677 in the
      IL6 locus was significantly associated with an increased white blood cell count,
      platelet count and serum globulin and a decreased mean corpuscular hemoglobin and
      mean corpuscular hemoglobin concentration (P < 5.0 * 10(-4)), although no
      pleiotropic association was observed in the CRP or HNF1A locus (alpha = 0.01).
      Our study demonstrated the pivotal role of the IL6 locus in the regulation of
      serum CRP levels and inflammatory pathways.

PMID- 21196491
TI  - The Na/K-ATPase is obligatory for membrane anchorage of retinoschisin, the
      protein involved in the pathogenesis of X-linked juvenile retinoschisis.
AB  - Mutations in the RS1 gene that encodes the discoidin domain containing
      retinoschisin cause X-linked juvenile retinoschisis (XLRS), a common macular
      degeneration in males. Disorganization of retinal layers and electroretinogram
      abnormalities are hallmarks of the disease and are also found in mice deficient
      for the orthologous murine protein, indicating that retinoschisin is important
      for the maintenance of retinal cell integrity. Upon secretion, retinoschisin
      associates with plasma membranes of photoreceptor and bipolar cells, although the
      components by which the protein is linked to membranes in vivo are still unclear.
      Here, we show that retinoschisin fails to bind to phospholipids or unilamellar
      lipid vesicles. A recent proteomic approach identified the Na/K-ATPase subunits
      ATP1A3 and ATP1B2 as binding partners of retinoschisin. We analyzed mice
      deficient for retinoschisin (Rs1h(-/Y)) and ATP1B2 (Atp1b2(-/-)) to characterize
      the role of Na/K-ATPase interaction in the organization of retinoschisin on
      cellular membranes. We demonstrate that both the Na/K-ATPase and retinoschisin
      are significantly reduced in Atp1b2(-/-) retinas, suggesting that retinoschisin
      membrane association is severely impaired in the absence of ATP1A3 and ATP1B2
      subunits. Conversely, the presence of ATP1A3 and ATP1B2 are obligatory for
      binding of exogenously applied retinoschisin to crude membranes. Also, co
      expression of ATP1A3 and ATP1B2 is required for retinoschisin binding to intact
      Hek293 cells. Taken together, our data support a predominant role of Na/K-ATPase
      in anchoring retinoschisin to retinal cell surfaces. Furthermore, altered
      localization of ATP1A3 and ATP1B2 is a notable consequence of retinoschisin
      deficiency and thus may be an important downstream aspect of cellular pathology
      in XLRS.

PMID- 21196493
TI  - MCM-BP regulates unloading of the MCM2-7 helicase in late S phase.
AB  - Origins of DNA replication are licensed by recruiting MCM2-7 to assemble the
      prereplicative complex (pre-RC). How MCM2-7 is inactivated or removed from
      chromatin at the end of S phase is still unclear. Here, we show that MCM-BP can
      disassemble the MCM2-7 complex and might function as an unloader of MCM2-7 from
      chromatin. In Xenopus egg extracts, MCM-BP exists in a stable complex with MCM7,
      but is not associated with the MCM2-7 hexameric complex. MCM-BP accumulates in
      nuclei in late S phase, well after the loading of MCM2-7 onto chromatin. MCM-BP
      immunodepletion in Xenopus egg extracts inhibits replication-dependent MCM
      dissociation without affecting pre-RC formation and DNA replication. When excess
      MCM-BP is incubated with Xenopus egg extracts or immunopurified MCM2-7, it binds
      to MCM proteins and promotes disassembly of the MCM2-7 complex. Recombinant MCM
      BP also releases MCM2-7 from isolated late-S-phase chromatin, but this activity
      is abolished when DNA replication is blocked. MCM-BP silencing in human cells
      also delays MCM dissociation in late S phase. We propose that MCM-BP plays a key
      role in the mechanism by which pre-RC is cleared from replicated DNA in
      vertebrate cells.

PMID- 21196494
TI  - miR-191 regulates mouse erythroblast enucleation by down-regulating Riok3 and
      Mxi1.
AB  - Using RNA-seq technology, we found that the majority of microRNAs (miRNAs)
      present in CFU-E erythroid progenitors are down-regulated during terminal
      erythroid differentiation. Of the developmentally down-regulated miRNAs, ectopic
      overexpression of miR-191 blocks erythroid enucleation but has minor effects on
      proliferation and differentiation. We identified two erythroid-enriched and
      developmentally up-regulated genes, Riok3 and Mxi1, as direct targets of miR-191.
      Knockdown of either Riok3 or Mxi1 blocks enucleation, and either physiological
      overexpression of miR-191 or knockdown of Riok3 or Mxi1 blocks chromatin
      condensation. Thus, down-regulation of miR-191 is essential for erythroid
      chromatin condensation and enucleation by allowing up-regulation of Riok3 and
      Mxi1.

PMID- 21196495
TI  - A qualitative study of attitudes toward public breastfeeding among young Canadian
      men and women.
AB  - This research aims to explore, in qualitative terms, attitudes held by a sample
      of university-educated young men and women residing in New Brunswick and Nova
      Scotia about breastfeeding in public places. In sum, 20 women and 27 men between
      the ages of 18 and 23 participated in moderated single-sex focus groups that
      discussed breastfeeding, following a list of prepared questions and using
      photographs as discussion cues. Although participants uniformly stated that they
      desired their future children to be breastfed, 31 of 47 expressed restrictive
      attitudes toward exposure of the breast (eg, "should use washrooms," "okay if
      discreet") and breastfeeding in restaurants. Eight expressed positive
      unrestricted statements about breastfeeding in public spaces. Addressing widely
      held attitudes toward breastfeeding in public spaces, in addition to providing
      information about breastfeeding's health benefits, may be helpful in campaigns
      promoting breastfeeding.

PMID- 21196496
TI  - The structure of NSD1 reveals an autoregulatory mechanism underlying histone
      H3K36 methylation.
AB  - The Sotos syndrome gene product, NSD1, is a SET domain histone methyltransferase
      that primarily dimethylates nucleosomal histone H3 lysine 36 (H3K36). To date,
      the intrinsic properties of NSD1 that determine its nucleosomal substrate
      selectivity and dimethyl H3K36 product specificity remain unknown. The 1.7 A
      structure of the catalytic domain of NSD1 presented here shows that a regulatory
      loop adopts a conformation that prevents free access of H3K36 to the bound S
      adenosyl-L-methionine. Molecular dynamics simulation and computational docking
      revealed that this normally inhibitory loop can adopt an active conformation,
      allowing H3K36 access to the active site, and that the nucleosome may stabilize
      the active conformation of the regulatory loop. Hence, our study reveals an
      autoregulatory mechanism of NSD1 and provides insight into the molecular
      mechanism of the nucleosomal substrate selectivity of this disease-related H3K36
      methyltransferase.

PMID- 21196498
TI  - Ethics for the pediatrician: physician interaction with the pharmaceutical
      industry.

PMID- 21196497
TI  - Acetylation-deacetylation of the transcription factor Nrf2 (nuclear factor
      erythroid 2-related factor 2) regulates its transcriptional activity and
      nucleocytoplasmic localization.
AB  - Activation of Nrf2 by covalent modifications that release it from its inhibitor
      protein Keap1 has been extensively documented. In contrast, covalent
      modifications that may regulate its action after its release from Keap1 have
      received little attention. Here we show that CREB-binding protein induced
      acetylation of Nrf2, increased binding of Nrf2 to its cognate response element in
      a target gene promoter, and increased Nrf2-dependent transcription from target
      gene promoters. Heterologous sirtuin 1 (SIRT1) decreased acetylation of Nrf2 as
      well as Nrf2-dependent gene transcription, and its effects were overridden by
      dominant negative SIRT1 (SIRT1-H355A). The SIRT1-selective inhibitors EX-527 and
      nicotinamide stimulated Nrf2-dependent gene transcription, whereas resveratrol, a
      putative activator of SIRT1, was inhibitory, mimicking the effect of SIRT1.
      Mutating lysine to alanine or to arginine at Lys(588) and Lys(591) of Nrf2
      resulted in decreased Nrf2-dependent gene transcription and abrogated the
      transcription-activating effect of CREB-binding protein. Furthermore, SIRT1 had
      no effect on transcription induced by these mutants, indicating that these sites
      are acetylation sites. Microscope imaging of GFP-Nrf2 in HepG2 cells as well as
      immunoblotting for Nrf2 showed that acetylation conditions resulted in increased
      nuclear localization of Nrf2, whereas deacetylation conditions enhanced its
      cytoplasmic rather than its nuclear localization. We posit that Nrf2 in the
      nucleus undergoes acetylation, resulting in binding, with basic-region leucine
      zipper protein(s), to the antioxidant response element and consequently in gene
      transcription, whereas deacetylation disengages it from the antioxidant response
      element, thereby resulting in transcriptional termination and subsequently in its
      nuclear export.

PMID- 21196499
TI  - Delayed tooth emergence.

PMID- 21196500
TI  - The pediatrician as teacher.

PMID- 21196501
TI  - Infants of drug-dependent mothers.

PMID- 21196502
TI  - Inflammatory bowel disease.

PMID- 21196503
TI  - Visual diagnosis: perceived fevers and back pain in a 1-week-old Infant.

PMID- 21196504
TI  - Focus on diagnosis: a primer on D-dimer.

PMID- 21196505
TI  - Pediatrics in the community: the Haiti earthquake.

PMID- 21196506
TI  - Index of suspicion . case 1: recurrent oral ulcers in an adolescent . case 2:
      visual impairment in an autistic child . case 3: fever and hepatosplenomegaly in
      an infant.

PMID- 21196507
TI  - Thrombotic disorders.

PMID- 21196508
TI  - Exact feature probabilities in images with occlusion.
AB  - To understand the computations of our visual system, it is important to
      understand also the natural environment it evolved to interpret. Unfortunately,
      existing models of the visual environment are either unrealistic or too complex
      for mathematical description. Here we describe a naturalistic image model and
      present a mathematical solution for the statistical relationships between the
      image features and model variables. The world described by this model is composed
      of independent, opaque, textured objects, which occlude each other. This simple
      structure allows us to calculate the joint probability distribution of image
      values sampled at multiple arbitrarily located points, without approximation.
      This result can be converted into probabilistic relationships between observable
      image features as well as between the unobservable properties that caused these
      features, including object boundaries and relative depth. We show that the image
      model is sufficient to explain a wide range of natural scene properties. Finally,
      we discuss the implications of this description of natural scenes for the study
      of vision.

PMID- 21196509
TI  - The development of spatial frequency discrimination.
AB  - We compared thresholds for discriminating spatial frequency for children aged 5,
      7, and 9 years, and adults at two baseline spatial frequencies (1 and 3 cpd). In
      Experiment 1, the minimum change from baseline necessary to detect a change in
      spatial frequency from either baseline decreased with age from 34% in 5-year-olds
      to 11% in 7-year-olds, 8% in 9-year-olds, and 6% in adults. The data were best
      fit by an exponential function reflecting the rapid improvement in thresholds
      between 5 and 7 years of age and more gradual improvement thereafter (r(2) =
      0.50, p < 0.0001). In Experiment 2, 5-year-olds' thresholds were higher than
      those of adults, even when memory demands were eliminated by presenting the two
      spatial frequencies side by side for an unlimited time. The pattern of
      development for sensitivity to spatial frequency (this study) resembles those for
      the development of sensitivity to orientation (T. L. Lewis, S. E. Chong, & D.
      Maurer, 2009) and contrast (D. Ellemberg, T. L. Lewis, C. H. Lui, & D. Maurer,
      1999). The similar patterns are consistent with theories of common underlying
      mechanisms in primary visual cortex (A. Vincent & D. Regan, 1995; W. Zhu, M.
      Shelley, & R. Shapley, 2008) and suggest that those mechanisms continue to
      develop throughout childhood.

PMID- 21196510
TI  - How attention and contrast gain control interact to regulate lightness contrast
      and assimilation: a computational neural model.
AB  - Recent theories of lightness perception assume that lightness (perceived
      reflectance) is computed by a process that contrasts the target's luminance with
      that of one or more regions in its spatial surround. A challenge for any such
      theory is the phenomenon of lightness assimilation, which occurs when increasing
      the luminance of a surround region increases the target lightness: the opposite
      of contrast. Here contrast and assimilation are studied quantitatively in
      lightness matching experiments utilizing concentric disk-and-ring displays.
      Whether contrast or assimilation is seen depends on a number of factors
      including: the luminance relations of the target, surround, and background;
      surround size; and matching instructions. When assimilation occurs, it is always
      part of a larger pattern in which assimilation and contrast both occur over
      different ranges of surround luminance. These findings are quantitatively modeled
      by a theory that assumes lightness is computed from a weighted sum of responses
      of edge detector neurons in visual cortex. The magnitude of the neural response
      to an edge is regulated by a combination of contrast gain control acting between
      neighboring edge detectors and a top-down attentional gain control that
      selectively weights the response to stimulus edges according to their task
      relevance.

PMID- 21196511
TI  - The effects of visuospatial attention measured across visual cortex using source
      imaged, steady-state EEG.
AB  - How does attention alter neural responses? Decades of electrophysiological
      measurements in non-human primates as well as human EEG and fMRI studies have
      shown that spatial attention modulates firing rates across the visual cortex, but
      the computations that drive this process are still unclear. Further, while it is
      well known that attention affects perception, we have only a limited
      understanding of the link between attentionally driven changes in neural firing
      rates and subject performance. Here we used a novel human neuroimaging method to
      measure the effect of spatial attention on neural responses in V1, hMT+, hV4, and
      the intraparietal sulcus (IPS). Attention altered signals in different ways
      across the visual cortex: areas V1, hMT+, and IPS exhibited primarily response
      gain changes while hV4 showed contrast gain modulation. Signals in V1, hMT+, and
      IPS correlated with contrast detection performance suggesting that behavior can
      be predicted by population-level signals as early as striate cortex.

PMID- 21196512
TI  - Breaking camouflage: binocular disparity reduces contrast masking in natural
      images.
AB  - Visual overlay masking is typically studied with a mask and target located at the
      same depth plane. Masking is reduced when binocular disparity separates the
      target from the mask (G. Moraglia & B. Schneider, 1990). We replicate this
      finding for a broadband target masked by natural images and find the greatest
      masking (threshold elevation) when target and mask occupy the same depth plane.
      Masking was reduced equally whether the target appeared at a crossed or an
      uncrossed disparity. We measure the tuning of masking and determine the extent of
      the benefit afforded by disparity. Threshold elevation decreases monotonically
      with increasing disparity until +/-8 arcmin. Two underlying components to the
      masking are evident; one accounts for around two-thirds of the masking and is
      independent of disparity. The second component is disparity-dependent and results
      in additional masking when there is zero disparity. Importantly, the reduction in
      masking with disparity cannot be explained by interocular decorrelation; we use a
      single-interval orientation discrimination task to exclude this possibility. We
      conclude that when the target and mask are presented at different depths they
      activate distinct populations of disparity-tuned neurons, resulting in less
      masking of the target.

PMID- 21196513
TI  - A model of natural image edge co-occurrence in the rototranslation group.
AB  - In this paper, we propose to model the edge information contained in natural
      scenes as points in the 3D space of positions and orientations. This space is
      equipped with a strong geometrical structure and it is identified as the
      rototranslation group. In this space, we compute a histogram of co-occurrence of
      edges from a database of natural images and show that it can be interpreted as a
      probability density function, expressed by the fundamental solution of a suitable
      Fokker-Planck equation defined in the 3D structured space. Both estimated
      statistics and model predictions are reconsidered and compared with the partial
      gestalt association fields proposed by D. J. Field, A. Hayes, and R. F. Hess
      (1993). Finally, parametric identification allows to estimate the variance of the
      co-occurrence random process in natural images.

PMID- 21196514
TI  - Loci of the release from fMRI adaptation for changes in facial expression,
      identity, and viewpoint.
AB  - Face recognition involves collaboration of a distributed network of neural
      correlates. However, how different attributes of faces are represented has
      remained unclear. We used functional magnetic resonance imaging-adaptation
      (fMRIa) to investigate the representation of viewpoint, expression, and identity
      of faces in the fusiform face area (FFA) and the occipital face area (OFA). In an
      event-related experiment, subjects viewed sequences of two faces and judged
      whether they depicted the same person. The images could vary in viewpoint,
      expression and/or identity. Critically, the physical similarity between view
      changed and between expression-changed faces of the same person were matched by
      the Gabor-jet metric, a measure that predicts almost perfectly the effects of
      image similarity on face discrimination performance. In FFA, changes of identity
      produced the largest release from adaptation followed by changes of expression;
      but the release caused by changes of viewpoint was smaller and not reliable. OFA
      was sensitive only to changes in identity, even when image changes produced by
      identity variations were matched to those of expression and orientation. These
      results suggest that FFA is involved in the perception of both identity and
      expression of faces, a result contrary to the hypothesis of independent
      processing of changeable and invariant attributes of faces in the face-processing
      network.

PMID- 21196515
TI  - Salience from the decision perspective: You know where it is before you know it
      is there.
AB  - In visual search for feature contrast ("odd-one-out") singletons, identical
      manipulations of salience, whether by varying target-distractor similarity or
      dimensional redundancy of target definition, had smaller effects on reaction
      times (RTs) for binary localization decisions than for yes/no detection
      decisions. According to formal models of binary decisions, identical differences
      in drift rates would yield larger RT differences for slow than for fast
      decisions. From this principle and the present findings, it follows that
      decisions on the presence of feature contrast singletons are slower than
      decisions on their location. This is at variance with two classes of standard
      models of visual search and object recognition that assume a serial cascade of
      first detection, then localization and identification of a target object, but
      also inconsistent with models assuming that as soon as a target is detected all
      its properties, spatial as well as non-spatial (e.g., its category), are
      available immediately. As an alternative, we propose a model of detection and
      localization tasks based on random walk processes, which can account for the
      present findings.

PMID- 21196516
TI  - Optical aberrations and alignment of the eye with age.
AB  - We explored the relative changes in ocular, corneal, and internal aberrations
      associated with normal aging with special emphasis in the role of ocular
      alignment and lens shape factor in the balance of aberrations. Ocular and corneal
      aberrations together with the angle kappa were measured for a 5-mm pupil diameter
      in 46 eyes with low refractive errors and ages ranging between 20 and 77 years.
      The root mean square (RMS) of the higher order ocular and corneal aberrations
      increased with age at a rate of 0.0032 MUm/year and 0.0015 MUm/year,
      respectively. While in young eyes the partial compensation of aberrations by the
      internal surfaces was clear, no significant difference was found between corneal
      and ocular RMS in the older group. The ocular spherical aberration (0.0011
      MUm/year) and horizontal coma (0.0017 MUm/year) increased moderately with age.
      This is not due to changes in the optical alignment, since angle kappa did not
      vary significantly with age. Age-related variations in the radii of curvature of
      the crystalline lens modify slightly its shape factor, reducing the compensation
      of lateral coma. This suggests that geometrical changes in the crystalline lens
      with age contribute to modify its aberration structure, reducing the compensation
      mechanism and explaining most of the measured increment of ocular aberrations
      with age.

PMID- 21196517
TI  - A genome-wide enhancer screen implicates sphingolipid composition in vacuolar
      ATPase function in Saccharomyces cerevisiae.
AB  - The function of the vacuolar H(+)-ATPase (V-ATPase) enzyme complex is to acidify
      organelles; this process is critical for a variety of cellular processes and has
      implications in human disease. There are five accessory proteins that assist in
      assembly of the membrane portion of the complex, the V(0) domain. To identify
      additional elements that affect V-ATPase assembly, trafficking, or enzyme
      activity, we performed a genome-wide enhancer screen in the budding yeast
      Saccharomyces cerevisiae with two mutant assembly factor alleles, VMA21 with a
      dysfunctional ER retrieval motif (vma21QQ) and vma21QQ in combination with
      voa1Delta, a nonessential assembly factor. These alleles serve as sensitized
      genetic backgrounds that have reduced V-ATPase enzyme activity. Genes were
      identified from a variety of cellular pathways including a large number of
      trafficking-related components; we characterized two redundant gene pairs,
      HPH1/HPH2 and ORM1/ORM2. Both sets demonstrated synthetic growth defects in
      combination with the vma21QQ allele. A loss of either the HPH or ORM gene pairs
      alone did not result in a decrease in vacuolar acidification or defects in V
      ATPase assembly. While the Hph proteins are not required for V-ATPase function,
      Orm1p and Orm2p are required for full V-ATPase enzyme function. Consistent with
      the documented role of the Orm proteins in sphingolipid regulation, we have found
      that inhibition of sphingolipid synthesis alleviates Orm-related growth defects.

PMID- 21196518
TI  - Rapid identification of a disease allele in mouse through whole genome sequencing
      and bulk segregation analysis.
AB  - In a pedigree of C57BL/6J mice homozygous for germline mutations induced by the
      mutagen N-ethyl-N-nitrosourea (ENU), numerous animals died under specific
      pathogen-free (SPF) conditions between 6 and 7 months of age. Death was caused by
      nephritic syndrome, which progressed to renal failure associated with focal
      segmental glomerulosclerosis. To identify the mutation responsible for renal
      disease, we sequenced genomic DNA from an affected animal using the Applied
      Biosystems SOLiD sequencing platform. Approximately 74% of the nucleotides
      comprising coding sequences and splice junctions in the mouse genome were covered
      at least three times. Within this portion of the genome, 64 discrepancies were
      flagged as potential homozygous mutations and 82 were flagged as potential
      heterozygous mutations. A total of 10 of these calls, all homozygous, were
      validated by capillary sequencing. One of the validated mutations disrupted
      splicing of the Col4a4 transcript. Genetic mapping by bulk segregation analysis
      excluded all mutations but this one as the cause of renal disease in Aoba mice.
      Col4a4 has not been targeted in the mouse, and this strain, named Aoba,
      represents the first functionally null allele in this species. Our study
      demonstrates the speed and utility of whole genome sequencing coupled with low
      resolution meiotic mapping as a means of identifying causative mutations induced
      by ENU.

PMID- 21196519
TI  - The activator/dissociation transposable elements comprise a two-component gene
      regulatory switch that controls endogenous gene expression in maize.
AB  - The maize Activator/Dissociation (Ac/Ds) elements are able to replicate and
      transpose throughout the maize genome. Both elements preferentially insert into
      gene-rich regions altering the maize genome by creating unstable insertion
      alleles, stable derivative or excision alleles, or by altering the spatial or
      temporal regulation of gene expression. Here, we characterize an Ac insertion in
      the 5'-UTR of the Pink Scutellum1 (Ps1) gene and five Ds derivatives generated
      through abortive transposition events. Characterization of Ps1 transcription
      initiation sites in this allelic series revealed several that began within the
      terminus of the Ac and Ds elements. Transcripts originating within Ds or Ac
      accumulated to lower levels than the wild-type Ps1 allele, but were often
      sufficient to rescue the seedling lethal phenotype associated with severe loss-of
      function alleles. Transcription initiation sites were similar in Ac and Ds
      derivatives, suggesting that Ac transposase does not influence transcript
      initiation site selection. However, we show that Ac transposase can negatively
      regulate Ps1 transcript accumulation in a subset of Ds-insertion alleles
      resulting in a severe mutant phenotype. The role of maize transposons in gene
      evolution is discussed.

PMID- 21196520
TI  - Analysis of B-genome chromosome introgression in interspecific hybrids of
      Brassica napus * B. carinata.
AB  - Brassica carinata, an allotetraploid with B and C genomes, has a number of traits
      that would be valuable to introgress into B. napus. Interspecific hybrids were
      created between B. carinata (BBCC) and B. napus (AACC), using an advanced
      backcross approach to identify and introgress traits of agronomic interest from
      the B. carinata genome and to study the genetic changes that occur during the
      introgression process. We mapped the B and C genomes of B. carinata with SSR
      markers and observed their introgression into B. napus through a number of
      backcross generations, focusing on a BC(3) and BC(3)S(1) sibling family. There
      was close colinearity between the C genomes of B. carinata and B. napus and we
      provide evidence that B. carinata C chromosomes pair and recombine normally with
      those of B. napus, suggesting that similar to other Brassica allotetraploids no
      major chromosomal rearrangements have taken place since the formation of B.
      carinata. There was no evidence of introgression of the B chromosomes into the A
      or C chromosomes of B. napus; instead they were inherited as whole linkage groups
      with the occasional loss of terminal segments and several of the B-genome
      chromosomes were retained across generations. Several BC(3)S(1) families were
      analyzed using SSR markers, genomic in situ hybridization (GISH) assays, and
      chromosome counts to study the inheritance of the B-genome chromosome(s) and
      their association with morphological traits. Our work provides an analysis of the
      behavior of chromosomes in an interspecific cross and reinforces the challenges
      of introgressing novel traits into crop plants.

PMID- 21196521
TI  - A genetical genomics approach to genome scans increases power for QTL mapping.
AB  - We describe a method for integrating gene expression information into genome
      scans and show that this can substantially increase the statistical power of QTL
      mapping. The method has three stages. First, standard clustering methods identify
      small (size 5-20) groups of genes with similar expression patterns. Second, each
      gene group is tested for a causative genetic locus shared with the clinical trait
      of interest. This is done using an EM algorithm approach that treats genotype at
      the putative causative locus as an unobserved variable and combines expression
      information from all of the genes in the group to infer genotype information at
      the locus. Finally, expression QTL (eQTL) are mapped for each gene group that
      shares a causative locus with the clinical trait. Such eQTL are candidates for
      the causative locus. Simulation results show that this method has far superior
      power to standard QTL mapping techniques in many circumstances. We applied this
      method to existing data on mouse obesity. Our method identified 27 putative body
      weight QTL, whereas standard QTL mapping produced only one. Furthermore, most
      gene groups with body weight QTL included cis genes, so candidate genes could be
      immediately identified. Eleven body weight QTL produced 16 candidate genes that
      have been previously associated with body weight or body weight-related traits,
      thus validating our method. In addition, 15 of the 16 other loci produced 32
      candidate genes that have not been associated with body weight. Thus, this method
      shows great promise for finding new causative loci for complex traits.

PMID- 21196522
TI  - Molecular evolution, mutation size and gene pleiotropy: a geometric
      reexamination.
AB  - The influence of phenotypic effects of genetic mutations on molecular evolution
      is not well understood. Neutral and nearly neutral theories of molecular
      evolution predict a negative relationship between the evolutionary rate of
      proteins and their functional importance; nevertheless empirical studies seeking
      relationships between evolutionary rate and the phenotypic role of proteins have
      not produced conclusive results. In particular, previous studies have not found
      the expected negative correlation between evolutionary rate and gene pleiotropy.
      Here, we studied the effect of gene pleiotropy and the phenotypic size of
      mutations on the evolutionary rate of genes in a geometrical model, in which gene
      pleiotropy was characterized by n molecular phenotypes that affect organismal
      fitness. For a nearly neutral process, we found a negative relationship between
      evolutionary rate and mutation size but pleiotropy did not affect the
      evolutionary rate. Further, for a selection model, where most of the
      substitutions were fixed by natural selection in a randomly fluctuating
      environment, we also found a negative relationship between evolutionary rate and
      mutation size, but interestingly, gene pleiotropy increased the evolutionary rate
      as ?n. These findings may explain part of the disagreement between empirical data
      and traditional expectations.

PMID- 21196523
TI  - New insight into the role of the Cdc34 ubiquitin-conjugating enzyme in cell cycle
      regulation via Ace2 and Sic1.
AB  - The Cdc34 ubiquitin-conjugating enzyme plays a central role in progression of the
      cell cycle. Through analysis of the phenotype of a mutant missing a highly
      conserved sequence motif within the catalytic domain of Cdc34, we discovered
      previously unrecognized levels of regulation of the Ace2 transcription factor and
      the cyclin-dependent protein kinase inhibitor Sic1. In cells carrying the
      Cdc34(tm) mutation, which alters the conserved sequence, the cyclin-dependent
      protein kinase inhibitor Sic1, an SCF(Cdc4) substrate, has a shorter half-life,
      while the cyclin Cln1, an SCF(Grr1) substrate, has a longer half-life than in
      wild-type cells. Expression of the SIC1 gene cluster, which is regulated by Swi5
      and Ace2 transcription factors, is induced in CDC34(tm) cells. Levels of Swi5,
      Ace2, and the SCF(Grr1) targets Cln1 and Cln2 are elevated in Cdc34(tm) cells,
      and loss of Grr1 causes an increase in Ace2 levels. Sic1 levels are similar in
      CDC34(tm) ace2Delta and wild-type cells, explaining a paradoxical increase in the
      steady-state level of Sic1 protein despite its reduced half-life. A screen for
      mutations that interact with CDC34(tm) uncovered novel regulators of Sic1,
      including genes encoding the polyubiquitin chain receptors Rad23 and Rpn10.

PMID- 21196524
TI  - Detecting directional selection in the presence of recent admixture in African
      Americans.
AB  - We investigate the performance of tests of neutrality in admixed populations
      using plausible demographic models for African-American history as well as
      resequencing data from African and African-American populations. The analysis of
      both simulated and human resequencing data suggests that recent admixture does
      not result in an excess of false-positive results for neutrality tests based on
      the frequency spectrum after accounting for the population growth in the parental
      African population. Furthermore, when simulating positive selection, Tajima's D,
      Fu and Li's D, and haplotype homozygosity have lower power to detect population
      specific selection using individuals sampled from the admixed population than
      from the nonadmixed population. Fay and Wu's H test, however, has more power to
      detect selection using individuals from the admixed population than from the
      nonadmixed population, especially when the selective sweep ended long ago. Our
      results have implications for interpreting recent genome-wide scans for positive
      selection in human populations.

PMID- 21196525
TI  - The LIN-15A and LIN-56 transcriptional regulators interact to negatively regulate
      EGF/Ras signaling in Caenorhabditis elegans vulval cell-fate determination.
AB  - The restricted expression of epidermal growth factor (EGF) family ligands is
      important for proper development and for preventing cancerous growth in mammals.
      In Caenorhabditis elegans, the class A and B synthetic multivulva (synMuv) genes
      redundantly repress expression of lin-3 EGF to negatively regulate Ras-mediated
      vulval development. The class B synMuv genes encode proteins homologous to
      components of the NuRD and Myb-MuvB/dREAM transcriptional repressor complexes,
      indicating that they likely silence lin-3 EGF through chromatin remodeling. The
      two class A synMuv genes cloned thus far, lin-8 and lin-15A, both encode novel
      proteins. The LIN-8 protein is nuclear. We have characterized the class A synMuv
      gene lin-56 and found it to encode a novel protein that shares a THAP-like C(2)CH
      motif with LIN-15A. Both the LIN-56 and LIN-15A proteins localize to nuclei. Wild
      type levels of LIN-56 require LIN-15A, and wild-type levels and/or localization
      of LIN-15A requires LIN-56. Furthermore, LIN-56 and LIN-15A interact in the yeast
      two-hybrid system. We propose that LIN-56 and LIN-15A associate in a nuclear
      complex that inhibits vulval specification by repressing lin-3 EGF expression.

PMID- 21196527
TI  - Classification of neural tumors in laboratory rodents, emphasizing the rat.
AB  - Neoplasms of the nervous system, whether spontaneous or induced, are infrequent
      in laboratory rodents and very rare in other laboratory animal species. The
      morphology of neural tumors depends on the intrinsic functions and properties of
      the cell type, the interactions between the neoplasm and surrounding normal
      tissue, and regressive changes. The incidence of neural neoplasms varies with
      sex, location, and age of tumor onset. Although the onset of spontaneous tumor
      development cannot be established in routine oncogenicity studies, calculations
      using the time of diagnosis (day of death) have revealed significant differences
      in tumor biology among different rat strains. In the central nervous system,
      granular cell tumors (a meningioma variant), followed by glial tumors, are the
      most common neoplasms in rats, whereas glial cell tumors are observed most
      frequently in mice. Central nervous system tumors usually affect the brain rather
      than the spinal cord. Other than adrenal gland pheochromocytomas, the most common
      neoplasms of the peripheral nervous system are schwannomas. Neural tumors may
      develop in the central nervous system and peripheral nervous system from other
      cell lineages (including extraneural elements like adipose tissue and
      lymphocytes), but such lesions are very rare in laboratory animals.

PMID- 21196526
TI  - Mechanism of chromosomal boundary action: roadblock, sink, or loop?
AB  - Boundary elements or insulators subdivide eukaryotic chromosomes into a series of
      structurally and functionally autonomous domains. They ensure that the action of
      enhancers and silencers is restricted to the domain in which these regulatory
      elements reside. Three models, the roadblock, sink/decoy, and topological loop,
      have been proposed to explain the insulating activity of boundary elements.
      Strong predictions about how boundaries will function in different experimental
      contexts can be drawn from these models. In the studies reported here, we have
      designed assays that test these predictions. The results of our assays are
      inconsistent with the expectations of the roadblock and sink models. Instead,
      they support the topological loop model.

PMID- 21196528
TI  - Assessing autonomic dysfunction symptoms in children: a pilot study.
AB  - As a screening tool to identify symptoms of autonomic dysfunction, the Pediatric
      Autonomic Symptoms Scale was administered to parents of children with familial
      dysautonomia, autism spectrum disorders, and age-matched controls. The total
      scores for the presence of symptoms were compared among the 3 groups for each
      section and overall. The Pediatric Autonomic Symptoms Scale distinguished
      controls from children with familial dysautonomia and autism spectrum disorders
      with scores from each section and overall scores. Familial dysautonomia children
      scored significantly higher in visceral symptoms, while children with autism
      spectrum disorders scored significantly higher in psychosocial symptoms. In
      familial dysautonomia, the concordance for the presence of symptoms within
      sections and overall scores ranged from 71% to 100%. The concordance for absence
      of autonomic dysfunction symptoms in controls ranged from 75% to 87.5%. The
      Pediatric Autonomic Symptoms Scale is comprehensive and can profile autonomic
      dysfunction in the 2 neurodevelopmental disorders. Its usefulness in other
      pediatric disorders remains to be studied.

PMID- 21196529
TI  - Juvenile Leigh syndrome, optic atrophy, ataxia, dystonia, and epilepsy due to
      T14487C mutation in the mtDNA-ND6 gene: a mitochondrial syndrome presenting from
      birth to adolescence.
AB  - An increasing number of reports describe mutations in mitochondrial DNA coding
      regions, especially in mitochondrial DNA- encoded nicotinamide adenine
      dinucleotide dehydrogenase subunit genes of the respiratory chain complex I, as
      causing early-onset Leigh syndrome. The authors report the molecular findings in
      a 24-year-old patient with juvenile-onset Leigh syndrome presenting with optic
      atrophy, ataxia dystonia, and epilepsy. A brain magnetic resonance imaging
      revealed bilateral basal ganglia and thalamic hypointensities, and a magnetic
      resonance spectroscopy revealed an increased lactate peak. The authors identified
      a T14487C change causing M63V substitution in the mitochondrial ND6 gene. The
      mutation was heteroplasmic in muscle and blood samples, with different mutation
      loads, and was absent in the patient's mother's urine and blood samples. They
      suggest that the T14487C mtDNA mutation should be analyzed in Leigh syndrome,
      presenting with optic atrophy, ataxia, dystonia, and epilepsy, regardless of age.

PMID- 21196530
TI  - The dynamical balance of the brain at rest.
AB  - The authors review evidence that spontaneous, that is, not stimulus or task
      driven, activity in the brain at the level of large-scale neural systems is not
      noise, but orderly and organized in a series of functional networks that
      maintain, at all times, a high level of coherence. These networks of spontaneous
      activity correlation or resting state networks (RSN) are closely related to the
      underlying anatomical connectivity, but their topography is also gated by the
      history of prior task activation. Network coherence does not depend on covert
      cognitive activity, but its strength and integrity relates to behavioral
      performance. Some RSN are functionally organized as dynamically competing systems
      both at rest and during tasks. Computational studies show that one of such
      dynamics, the anticorrelation between networks, depends on noise-driven
      transitions between different multistable cluster synchronization states. These
      multistable states emerge because of transmission delays between regions that are
      modeled as coupled oscillators systems. Large-scale systems dynamics are useful
      for keeping different functional subnetworks in a state of heightened
      competition, which can be stabilized and fired by even small modulations of
      either sensory or internal signals.

PMID- 21196531
TI  - Association of frontal subcortical circuits infarcts in poststroke depression: a
      magnetic resonance imaging study of 591 Chinese patients with ischemic stroke.
AB  - Despite extensive research into poststroke depression (PSD), the role played by
      lesion location in the pathogenesis of PSD remains uncertain. The aim of this
      study was to estimate the magnetic resonance imaging (MRI) correlates of PSD in
      Chinese patients with first or recurrent stroke. A total of 591 patients with
      acute ischemic stroke admitted to the acute stroke unit of a university
      affiliated regional hospital in Hong Kong were recruited. A psychiatrist assessed
      all the patients 3 months after the stroke. The psychiatrist used the Structured
      Clinical Interview for Diagnostic and Statistical Manual, fourth edition (DSM-IV)
      to confirm whether the patients met the criteria of a depressive disorder. In
      addition, a host of demographic, clinical, and radiological variables were
      examined. A tota; of 475 and 116 patients had first and recurrent strokes,
      respectively. In all, 75 (12.7%) patients received a diagnosis of PSD. In
      univariate analysis of the MRI findings, the presence of infarcts in the frontal
      subcortical circuits ([FSC], 66.7% vs 53.3%) was significantly associated with
      PSD (P = .03) compared to the patients without PSD. The FSC infarct-PSD
      association remained significant (odds ratio = 2.6) in subsequent logistic
      regression analysis after adjusting for gender, history of depression,
      neurological impairment, level of social support, and major life events. In
      conclusion, FSC infarcts are independent predictors of PSD. Further work is
      needed to clarify whether these infarcts have an impact on the clinical
      presentation, treatment responses, and prognosis of PSD.

PMID- 21196533
TI  - Young children share the spoils after collaboration.
AB  - Egalitarian behavior is considered to be a species-typical component of human
      cooperation. Human adults tend to share resources equally, even if they have the
      opportunity to keep a larger portion for themselves. Recent experiments have
      suggested that this tendency emerges fairly late in human ontogeny, not before 6
      or 7 years of age. Here we show that 3-year-old children share mostly equally
      with a peer after they have worked together actively to obtain rewards in a
      collaboration task, even when those rewards could easily be monopolized. These
      findings contrast with previous findings from a similar experiment with
      chimpanzees, who tended to monopolize resources whenever they could. The
      potentially species-unique tendency of humans to share equally emerges early in
      ontogeny, perhaps originating in collaborative interactions among peers.

PMID- 21196534
TI  - What's in a name?: popular names are less common on frontiers.
AB  - Voluntary settlement on a frontier may promote values of independence. At
      present, however, researchers know little about the behavioral consequences of
      this process. In this study, we examined regional variations in baby naming.
      Because baby naming is an act of considerable personal and familial significance,
      it reflects prevalent cultural values. In support of the hypothesized link
      between frontier settlement and independence, we found that babies receive
      popular names less frequently in western regions of the United States than in its
      eastern regions (Study 1). The same pattern holds in Canada (Study 2), with
      popular names being less frequent in western provinces than in eastern provinces.
      Moreover, popular names are less frequently given to babies in world regions in
      which Europeans have settled (e.g., Australia, the United States) than in
      European countries (Study 3). These findings have implications for cross
      generational transmission of cultural values.

PMID- 21196532
TI  - Janus kinase activation by cytokine oncostatin M decreases PCSK9 expression in
      liver cells.
AB  - PCSK9 degrades LDL receptor (LDLR) in liver and thereby influences the
      circulating level of LDL cholesterol. Hence, mechanisms inhibiting PCSK9
      expression have potential for cholesterol-lowering intervention. Previously, we
      demonstrated that oncostatin M (OM) activates LDLR gene transcription, resulting
      in an increased LDL uptake in HepG2 cells and a reduction of plasma LDL in
      hypercholesterolemic hamsters. Here we identify the suppression of PCSK9
      expression by OM as one new mechanism that increases LDLR protein in HepG2 cells.
      Treating HepG2 cells with OM decreases PCSK9 mRNA and protein levels. Inhibition
      studies and small interfering RNA -targeted depletion revealed a critical role
      for JAK1 and JAK2 in mediating this OM inhibitory effect. Furthermore, we showed
      that OM induces transient phosphorylation of STAT1, STAT3, and STAT5 and
      sustained activation of ERK signaling molecules. While depletion of STAT members
      in HepG2 cells did not affect OM inhibitory activity on PCSK9 expression,
      blocking activation of the MEK1/ERK signaling pathway resulted in attenuation of
      the OM inhibitory effect. Finally, by using an anti-hamster PCSK9 antibody, we
      demonstrated the in vivo suppression of liver PCSK9 mRNA and protein expression
      by OM in hypercholesterolemic hamsters. Our study uncovered a cytokine-triggered
      regulatory network for PCSK9 expression that is linked to JAKs and the ERK
      signaling pathway.

PMID- 21196536
TI  - Proximal humeral fractures: current concepts in classification, treatment and
      outcomes.
AB  - Most proximal humeral fractures are stable injuries of the ageing population, and
      can be successfully treated non-operatively. The management of the smaller number
      of more complex displaced fractures is more controversial and new fixation
      techniques have greatly increased the range of fractures that may benefit from
      surgery. This article explores current concepts in the classification and
      clinical aspects of these injuries, reviewing the indications, innovations and
      outcomes for the most common methods of treatment.

PMID- 21196537
TI  - Guided growth: recent advances in a deep-rooted concept.
AB  - Guiding growth by harnessing the ability of growing bone to undergo plastic
      deformation is one of the oldest orthopaedic principles. Correction of deformity
      remains a major part of the workload for paediatric orthopaedic surgeons and
      recently, along with developments in limb reconstruction and computer-directed
      frame correction, there has been renewed interest in surgical methods of physeal
      manipulation or 'guided growth'. Manipulating natural bone growth to correct a
      deformity is appealing, as it allows gradual correction by non- or minimally
      invasive methods. This paper reviews the techniques employed for guided growth in
      current orthopaedic practice, including the basic science and recent advances
      underlying mechanical physeal manipulation of both healthy and pathological
      physes.

PMID- 21196538
TI  - Cementless revision for infected total hip replacements.
AB  - Our aim was to determine the success rate of repeated debridement and two-stage
      cementless revision arthroplasty according to the type of infected total hip
      replacement (THR). We enrolled 294 patients (294 hips) with an infected THR in
      the study. There were 222 men and 72 women with a mean age of 55.1 years (24.0 to
      78.0). The rate of control of infection after the initial treatment and after
      repeated debridement and two-stage revisions was determined. The clinical (Harris
      hip score) and radiological results were evaluated. The mean follow-up was 10.4
      years (5.0 to 14.0). The eventual rate of control of infection was 100.0% for
      early superficial post-operative infection, 98.4% for early deep post-operative
      infection, 98.5% for late chronic infection and 91.0% for acute haematogenous
      infection. Overall, 288 patients (98%) maintained a functioning THR at the latest
      follow-up. All the allografts appeared to be united and there were no failures.
      These techniques effectively controlled infection and maintained a functional THR
      with firm fixation in most patients. Repeated debridement and two-stage or
      repeated two-stage revisions further improved the rate of control of infection
      after the initial treatment and increased the likelihood of maintaining a
      functional THR.

PMID- 21196539
TI  - Birmingham hip resurfacing: a minimum follow-up of ten years.
AB  - We report the survival, radiological and functional outcomes of a single surgeon
      series of his first 144 consecutive Birmingham hip resurfacing procedures (130
      patients) at a minimum of ten years. There were ten revisions during this time.
      Although no patients were lost to follow-up some did not complete the scoring
      assessment or undergo radiological assessment at ten years. The ten-year survival
      for male patients was 98.0% (95% confidence interval 95.2 to 100). The ten-year
      survival for the total cohort with aseptic revision as the endpoint was 95.5%
      (95% confidence interval 91.8 to 99.0) and including revisions for sepsis was
      93.5% (95% confidence interval 89.2 to 97.6). The median modified Oxford hip
      score at ten years was 4.2% (interquartile range 0 to 19) and the median
      University of California, Los Angeles score was 7.0 (interquartile range 5.0 to
      8.0). This study confirms the midterm reports that metal-on-metal hip resurfacing
      using the Birmingham Hip provides a durable alternative to total hip replacement,
      particularly in younger male patients wishing to maintain a high level of
      function, with low risk of revision for at least ten years.

PMID- 21196540
TI  - Treatment of Crowe IV high hip dysplasia with total hip replacement using the
      Exeter stem and shortening derotational subtrochanteric osteotomy.
AB  - We evaluated all cases involving the combined use of a subtrochanteric
      derotational femoral shortening osteotomy with a cemented Exeter stem performed
      at our institution. With severe developmental dysplasia of the hip an osteotomy
      is often necessary to achieve shortening and derotation of the proximal femur.
      Reduction can be maintained with a 3.5 mm compression plate while the implant is
      cemented into place. Such a plate was used to stabilise the osteotomy in all
      cases. Intramedullary autograft helps to prevent cement interposition at the
      osteotomy site and promotes healing. There were 15 female patients (18 hips) with
      a mean age of 51 years (33 to 75) who had a Crowe IV dysplasia of the hip and
      were followed up for a mean of 114 months (52 to 168). None was lost to follow
      up. All clinical scores were collected prospectively. The Charnley modification
      of the Merle D'Aubigne-Postel scores for pain, function and range of movement
      showed a statistically significant improvement from a mean of 2.4 (1 to 4), 2.3
      (1 to 4), 3.4 (1 to 6) to 5.2 (3 to 6), 4.4 (3 to 6), 5.2 (4 to 6), respectively.
      Three acetabular revisions were required for aseptic loosening; one required
      femoral revision for access. One osteotomy failed to unite at 14 months and was
      revised successfully. No other case required a femoral revision. No postoperative
      sciatic nerve palsy was observed. Cemented Exeter femoral components perform well
      in the treatment of Crowe IV dysplasia with this procedure.

PMID- 21196541
TI  - Systematic review and meta-analysis of the use of tranexamic acid in total hip
      replacement.
AB  - We report a systematic review and meta-analysis of published randomised
      controlled trials evaluating the efficacy of tranexamic acid (TXA) in reducing
      blood loss and transfusion in total hip replacement (THR). The data were
      evaluated using the generic evaluation tool designed by the Cochrane Bone, Joint
      and Muscle Trauma Group. We identified 11 clinical trials which were suitable for
      detailed extraction of data. There were no trials that used TXA in revision THR.
      A total of seven studies (comprising 350 patients) were eligible for the blood
      loss outcome data. The use of TXA reduced intra-operative blood loss by a mean of
      104 ml (95% confidence interval (CI) -164 to -44, p = 0.0006, heterogeneity I(2)
      0%), postoperative blood loss by a mean of 172 ml (95% CI -263 to -81, p =
      0.0002, heterogeneity I(2) 63%) and total blood loss by a mean of 289 ml (95% CI 
      440 to -138, p < 0.0002, heterogeneity I(2) 54%). TXA led to a significant
      reduction in the proportion of patients requiring allogeneic blood transfusion
      (risk difference -0.20, 95% CI -0.29 to -0.11, p < 0.00001, I(2) 15%). There were
      no significant differences in deep-vein thrombosis, pulmonary embolism, infection
      rates or other complications among the study groups.

PMID- 21196542
TI  - Symptomatic pulmonary embolism after outpatient arthroscopic procedures of the
      knee: the incidence and risk factors in 418,323 arthroscopies.
AB  - Pulmonary embolism is a serious complication after arthroscopy of the knee, about
      which there is limited information. We have identified the incidence and risk
      factors for symptomatic pulmonary embolism after arthroscopic procedures on
      outpatients. The New York State Department of Health Statewide Planning and
      Research Cooperative System database was used to review arthroscopic procedures
      of the knee performed on outpatients between 1997 and 2006, and identify those
      admitted within 90 days of surgery with an associated diagnosis of pulmonary
      embolism. Potential risk factors included age, gender, complexity of surgery,
      operating time defined as the total time that the patient was actually in the
      operating room, history of cancer, comorbidities, and the type of anaesthesia. We
      identified 374,033 patients who underwent 418,323 outpatient arthroscopies of the
      knee. There were 117 events of pulmonary embolism (2.8 cases for every 10 000
      arthroscopies). Logistic regression analysis showed that age and operating time
      had significant dose-response increases in risk (p < 0.001) for a subsequent
      admission with a pulmonary embolism. Female gender was associated with a 1.5-fold
      increase in risk (p = 0.03), and a history of cancer with a threefold increase (p
      = 0.05). These risk factors can be used when obtaining informed consent before
      surgery, to elevate the level of clinical suspicion of pulmonary embolism in
      patients at risk, and to establish a rationale for prospective studies to test
      the clinical benefit of thromboprophylaxis in high-risk patients.

PMID- 21196543
TI  - Combined technique for the correction of lower-limb deformities resulting from
      metabolic bone disease.
AB  - We present the results of the surgical correction of lower-limb deformities
      caused by metabolic bone disease. Our series consisted of 17 patients with a
      diagnosis of hypophosphataemic rickets and two with renal osteodystrophy; their
      mean age was 25.6 years (14 to 57). In all, 43 lower-limb segments (27 femora and
      16 tibiae) were osteotomised and the deformity corrected using a monolateral
      external fixator. The segment was then stabilised with locked intramedullary
      nailing. In addition, six femora in three patients were subsequently lengthened
      by distraction osteogenesis. The mean follow-up was 60 months (18 to 120). The
      frontal alignment parameters (the mechanical axis deviation, the lateral distal
      femoral angle and the medial proximal tibial angle) and the sagittal alignment
      parameters (the posterior distal femoral angle and the posterior proximal tibial
      angle) improved post-operatively. The external fixator was removed either at the
      end of surgery or at the end of the lengthening period, allowing for early
      mobilisation and weight-bearing. We encountered five problems and four obstacles
      in the programme of treatment. The use of intramedullary nails prevented
      recurrence of deformity and refracture.

PMID- 21196544
TI  - The Delta III reverse shoulder replacement for cuff tear arthropathy: a single
      centre study of 50 consecutive procedures.
AB  - The combination of an irreparable tear of the rotator cuff and destructive
      arthritis of the shoulder joint may cause severe pain, disability and loss of
      independence in the aged. Standard anatomical shoulder replacements depend on a
      functioning rotator cuff, and hence may fail in the presence of tears in the
      cuff. Many designs of non-anatomical constrained or semi-constrained prostheses
      have been developed for cuff tear arthropathy, but have proved unsatisfactory and
      were abandoned. The DePuy Delta III reverse prosthesis, designed by Grammont,
      medialises and stabilises the centre of rotation of the shoulder joint and has
      shown early promise. This study evaluated the mid-term clinical and radiological
      results of this arthroplasty in a consecutive series of 50 shoulders in 43
      patients with a painful pseudoparalysis due to an irreparable cuff tear and
      destructive arthritis, performed over a period of seven years by a single
      surgeon. A follow-up of 98% was achieved, with a mean duration of 39 months (8 to
      81). The mean age of the patients at the time of surgery was 81 years (59 to 95).
      The female to male ratio was 5:1. During the seven years, six patients died of
      natural causes. The clinical outcome was assessed using the American Shoulder and
      Elbow score, the Oxford Shoulder Score and the Short-form 36 score. A
      radiological review was performed using the Sirveaux score for scapular notching.
      The mean American Shoulder and Elbow score was 19 (95% confidence interval (CI)
      14 to 23) pre-operatively, and 65 (95% CI 48 to 82) (paired t-test, p < 0.001) at
      final follow-up. The mean Oxford score was 44 (95% CI 40 to 51) pre-operatively
      and 23 (95% CI 18 to 28) (paired t-test, p < 0.001) at final follow-up. The mean
      maximum elevation improved from 55 degrees  pre-operatively to 105 degrees  at
      final follow-up. There were seven complications during the whole series, although
      only four patients required further surgery.

PMID- 21196545
TI  - Injuries to the spinal accessory nerve: a lesson to surgeons.
AB  - The integrity of the spinal accessory nerve is fundamental to thoracoscapular
      function and essential for scapulohumeral rhythm. This nerve is vulnerable along
      its superficial course. This study assessed the delay in diagnosis and referral
      for management of damage to this nerve, clarified its anatomical course and
      function, and documented the results of repair. From examination of our records,
      111 patients with lesions of the spinal accessory nerve were treated between 1984
      and 2007. In 89 patients (80.2%) the damage was iatropathic. Recognition and
      referral were seldom made by the surgeon responsible for the injury, leading to a
      marked delay in instituting treatment. Most referrals were made for painful loss
      of shoulder function. The clinical diagnosis is straightforward. There is a
      characteristic downward and lateral displacement of the scapula, with narrowing
      of the inferior scapulohumeral angle and loss of function, with pain commonly
      present. In all, 80 nerves were explored and 65 were repaired. The course of the
      spinal accessory nerve in relation to the sternocleidomastoid muscle was
      constant, with branches from the cervical plexus rarely conveying motor fibres.
      Damage to the nerve was predominantly posterior to this muscle. Despite the
      delay, the results of repair were surprising, with early relief of pain, implying
      a neuropathic source, which preceded generally good recovery of muscle function.

PMID- 21196546
TI  - Long-term results of tension-band laminoplasty for cervical stenotic myelopathy:
      a ten-year follow-up.
AB  - We reviewed 75 patients (57 men and 18 women), who had undergone tension-band
      laminoplasty for cervical spondylotic myelopathy (42 patients) or compression
      myelopathy due to ossification of the posterior longitudinal ligament (33
      patients) and had been followed for more than ten years. Clinical and functional
      results were estimated using the Japanese Orthopaedic Association score. The rate
      of recovery and the level of postoperative axial neck pain were also recorded.
      The pre- and post-operative alignment of the cervical spine (Ishihara curve index
      indicating lordosis of the cervical spine) and the range of movement (ROM) of the
      cervical spine were also measured. The mean rate of recovery of the Japanese
      Orthopaedic Association score at final follow-up was 52.1% (SD 24.6) and
      significant axial pain was reported by 19 patients (25.3%). Axial pain was
      reported more frequently in patients with ossification of the posterior
      longitudinal ligament than in those with cervical spondylotic myelopathy (p =
      0.027). A kyphotic deformity was not seen post-operatively in any patient. The
      mean ROM decreased post-operatively from 32.8 degrees  (SD 12.3) to 16.2 degrees 
      (SD 12.3) (p < 0.001). The mean ROM ratio was 46.9% (SD 28.1) for all the
      patients. The mean ROM ratio was lower in patients with ossification of the
      posterior longitudinal ligament than in those with cervical spondylotic
      myelopathy (p < 0.001). Compared to those with cervical spondylotic myelopathy,
      patients with ossification of the posterior longitudinal ligament had less ROM
      and more post-operative axial neck pain.

PMID- 21196547
TI  - Repair of spondylolysis using compression with a modular link and screws.
AB  - We describe the results of a prospective case series of patients with
      spondylolysis, evaluating a technique of direct stabilisation of the pars
      interarticularis with a construct that consists of a pair of pedicle screws
      connected by a U-shaped modular link passing beneath the spinous process.
      Tightening the link to the screws compresses bone graft in the defect in the
      pars, providing rigid intrasegmental fixation. We have carried out this procedure
      on 20 patients aged between nine and 21 years with a defect of the pars at L5,
      confirmed on CT. The mean age of the patients was 13.9 years (9 to 21). They had
      a grade I or less spondylolisthesis and no evidence of intervertebral
      degeneration on MRI. The mean follow-up was four years (2.3 to 7.3). The patients
      were assessed by the Oswestry Disability Index (ODI) and a visual analogue scale
      (VAS). At the latest follow-up, 18 patients had an excellent clinical outcome,
      with a significant (p < 0.001) improvement in their ODI and VAS scores. The mean
      ODI score at final follow-up was 8%. Assessment of the defect by CT showed a rate
      of union of 80%. There were no complications involving the internal fixation. The
      strength of the construct removes the need for post-operative immobilisation.

PMID- 21196548
TI  - Open reduction and internal fixation of a traumatic diastasis of the pubic
      symphysis: one-year radiological and functional outcomes.
AB  - The aim of this study was to review the number of patients operated on for
      traumatic disruption of the pubic symphysis who developed radiological signs of
      movement of the anterior pelvic metalwork during the first post-operative year,
      and to determine whether this had clinical implications. A consecutive series of
      49 patients undergoing internal fixation of a traumatic diastasis of the pubic
      symphysis were studied. All underwent anterior fixation of the diastasis, which
      was frequently combined with posterior pelvic fixation. The fractures were
      divided into groups using the Young and Burgess classification for pelvic ring
      fractures. The different combinations of anterior and posterior fixation adopted
      to stabilise the fractures and the type of movement of the metalwork which was
      observed were analysed and related to functional outcome during the first post
      operative year. In 15 patients the radiographs showed movement of the anterior
      metalwork, with broken or mobile screws or plates, and in six there were signs of
      a recurrent diastasis. In this group, four patients required revision surgery;
      three with anterior fixation and one with removal of anterior pelvic metalwork;
      the remaining 11 functioned as well as the rest of the study group. We conclude
      that radiological signs of movement in the anterior pelvic metalwork, albeit
      common, are not in themselves an indication for revision surgery.

PMID- 21196549
TI  - Does the use of laminar flow and space suits reduce early deep infection after
      total hip and knee replacement?: the ten-year results of the New Zealand Joint
      Registry.
AB  - We have investigated whether the use of laminar-flow theatres and space suits
      reduced the rate of revision for early deep infection after total hip (THR) and
      knee (TKR) replacement by reviewing the results of the New Zealand Joint Registry
      at ten years. Of the 51 485 primary THRs and 36 826 primary TKRs analysed,
      laminar-flow theatres were used in 35.5% and space suits in 23.5%. For THR there
      was a significant increase in early infection in those procedures performed with
      the use of a space suit compared with those without (p < 0.0001), in those
      carried out in a laminar-flow theatre compared with a conventional theatre (p <
      0.003) and in those undertaken in a laminar-flow theatre with a space suit (p <
      0.001) when compared with conventional theatres without such a suit. The results
      were similar for TKR with the use of a space suit (p < 0.001), in laminar-flow
      theatres (p < 0.019) and when space suits were used in those theatres (p <
      0.001). These findings were independent of age, disease and operating time and
      were unchanged when the surgeons and hospital were analysed individually. The
      rate of revision for early deep infection has not been reduced by using laminar
      flow and space suits. Our results question the rationale for their increasing use
      in routine joint replacement, where the added cost to the health system seems to
      be unjustified.

PMID- 21196550
TI  - Return to theatre following total hip and knee replacement, before and after the
      introduction of rivaroxaban: a retrospective cohort study.
AB  - Rivaroxaban has been recommended for routine use as a thromboprophylactic agent
      in patients undergoing lower-limb arthroplasty. However, trials supporting its
      use have not fully evaluated the risks of wound complications. This study of 1048
      total hip/knee replacements records the rates of return to theatre and infection
      before and after the change from a low molecular weight heparin (tinzaparin) to
      rivaroxaban as the agent of chemical thromboprophylaxis in patients undergoing
      lower-limb arthroplasty. During a period of 13 months, 489 consecutive patients
      undergoing lower-limb arthroplasty received tinzaparin and the next 559
      consecutive patients received rivaroxaban as thromboprophylaxis. Nine patients in
      the control (tinzaparin) group (1.8%, 95% confidence interval 0.9 to 3.5)
      returned to theatre with wound complications within 30 days, compared with 22
      patients in the rivaroxaban group (3.94%, 95% confidence interval 2.6 to 5.9).
      This increase was statistically significant (p = 0.046). The proportion of
      patients who returned to theatre and became infected remained similar (p = 0.10).
      Our study demonstrates the need for further randomised controlled clinical trials
      to be conducted to assess the safety and efficacy of rivaroxaban in clinical
      practice, focusing on the surgical complications as well as the potential
      prevention of venous thromboembolism.

PMID- 21196551
TI  - The risk of peri-prosthetic fracture after primary and revision total hip and
      knee replacement.
AB  - Peri-prosthetic fracture after joint replacement in the lower limb is associated
      with significant morbidity. The primary aim of this study was to investigate the
      incidence of peri-prosthetic fracture after total hip replacement (THR) and total
      knee replacement (TKR) over a ten-year period using a population-based linked
      dataset. Between 1 April 1997 and 31 March 2008, 52,136 primary THRs, 8726
      revision THRs, 44,511 primary TKRs, and 3222 revision TKRs were performed. Five
      years post-operatively, the rate of fracture was 0.9% after primary THR, 4.2%
      after revision THR, 0.6% after primary TKR and 1.7% after revision TKR.
      Comparison of survival analysis for all primary and revision arthroplasties
      showed peri-prosthetic fractures were more likely in females, patients aged > 70
      and after revision arthroplasty. Female patients aged > 70 should be warned of a
      significantly increased risk of peri-prosthetic fracture after hip or knee
      replacement. The use of adjuvant medical treatment to reduce the effect of peri
      prosthetic osteoporosis may be a direction of research for these patients.

PMID- 21196552
TI  - Glenoplasty for complex shoulder subluxation and dislocation in children with
      obstetric brachial plexus palsy.
AB  - We describe the early results of glenoplasty as part of the technique of
      operative reduction of posterior dislocation of the shoulder in 29 children with
      obstetric brachial plexus palsy. The mean age at operation was five years (1 to
      18) and they were followed up for a mean of 34 months (12 to 67). The mean Mallet
      score increased from 8 (5 to 13) to 12 (8 to 15) at final follow-up (p < 0.001).
      The mean passive forward flexion was increased by 18 degrees  (p = 0.017) and the
      mean passive abduction by 24 degrees  (p = 0.001). The mean passive lateral
      rotation also increased by 54 degrees  (p < 0.001), but passive medial rotation
      was reduced by a mean of only 7 degrees . One patient required two further
      operations. Glenohumeral stability was achieved in all cases.

PMID- 21196553
TI  - A shelf procedure at a follow-up of 75 years.
AB  - Developmental dysplasia of the hip predisposes to premature degenerative hip
      disease. A number of operations have been described to improve acetabular cover
      and have achieved varying degrees of success. We present the case of an 84-year
      old woman, who underwent a shelf procedure to reconstruct a dysplastic hip 75
      years ago. To date, the shelf remains intact and the hip is asymptomatic. We
      believe this represents the longest documented outcome of any procedure to
      stabilise the hip.

PMID- 21196554
TI  - Costo-osteochondral graft for post-traumatic osteonecrosis of the radial head in
      an adolescent boy.
AB  - We present a case of post-traumatic osteonecrosis of the radial head in a 13-year
      old boy which was treated with costo-osteochondral grafts. A satisfactory outcome
      was seen at a follow-up of two years and ten months. Although costo-osteochondral
      grafting has been used in the treatment of defects in articular cartilage,
      especially in the hand and the elbow, the extension of the technique to manage
      post-traumatic osteonecrosis of the radial head in a child has not previously
      been reported in the English language literature. Complete relief of pain was
      obtained and an improvement in the range of movement was observed. The long-term
      results remain uncertain.

PMID- 21196555
TI  - The instruments of the bonesetter.
AB  - Orthopaedic surgeons use a variety of instruments to help correct, treat, and
      heal bone disease. The development of these instruments mirrors the history of
      orthopaedic surgery. The history of bonesetting, the treatment and replacement of
      joints, and of those who performed these techniques, appears to originate deep in
      antiquity. Changing ideas within medicine and surgery over the last 200 years
      have shaped the discovery and evolution of orthopaedic instruments and of the
      bonesetters themselves. Advances have led to the use of computers as instruments
      in the navigational guidance of arthroplasty surgery, the use of robotics, the
      development of cordless drills and improvements in the design of blades to cut
      bone. Yet some of the old instruments remain; plaster of Paris bandages, the
      Thomas Splint, Liston's bonecutter, Gigli's saw, bone nibblers and Macewan's
      osteotomes are still in use. This paper presents a historical review of
      bonesetters and examines how orthopaedic instruments have evolved from antiquity
      to the 21st century.

PMID- 21196556
TI  - High tibial osteotomy using polycaprolactone-tricalcium phosphate polymer wedge
      in a micro pig model.
AB  - Medial open-wedge high tibial osteotomy has been gaining popularity in recent
      years, but adequate supporting material is required in the osteotomy gap for
      early weight-bearing and rapid union. The purpose of this study was to
      investigate whether the implantation of a polycaprolactone-tricalcium phosphate
      composite scaffold wedge would enhance healing of the osteotomy in a micro pig
      model. We carried out open-wedge high tibial osteotomies in 12 micro pigs aged
      from 12 to 16 months. A scaffold wedge was inserted into six of the osteotomies
      while the other six were left open. Bone healing was evaluated after three and
      six months using plain radiographs, CT scans, measurement of the bone mineral
      density and histological examination. Complete bone union was obtained at six
      months in both groups. There was no collapse at the osteotomy site, loss of
      correction or failure of fixation in either group. Staining with haematoxylin and
      eosin demonstrated that there was infiltration of new bone tissue into the
      macropores and along the periphery of the implanted scaffold in the scaffold
      group. The CT scans and measurement of the bone mineral density showed that at
      six months specimens in the scaffold group had a higher bone mineral density than
      in the control group, although the implantation of the polycaprolactone
      tricalcium phosphate composite scaffold wedge did not enhance healing of the
      osteotomy.

PMID- 21196557
TI  - In vitro study of the antimicrobial effects of radiological contrast agents used
      in arthrography.
AB  - Aspiration arthrography using an iodinated contrast medium is a useful tool for
      the investigation of septic or aseptic loosening of arthroplasties and of septic
      arthritis. Previously, the contrast media have been thought to cause false
      negative results in cultures when present in aspirated samples of synovial fluid,
      probably because free iodine is bactericidal, but reports have been inconclusive.
      We examined the influence of the older, high osmolar contrast agents and the low
      osmolar media used currently on the growth of ten different micro-organisms
      capable of causing deep infection around a prosthesis. Five media were tested,
      using a disc diffusion technique and a time-killing curve method in which high
      and low inocula of micro-organisms were incubated in undiluted media. The only
      bactericidal effects were found with low inocula of Escherichia coli and
      Pseudomonas aeruginosa in ioxithalamate, one of the older ionic media. The low
      and iso-osmolar iodinated contrast media used currently do not impede culture.
      Future study must assess other causes of false negative cultures of synovial
      fluid and new developments in enhancing microbial recovery from aspirated
      samples.

PMID- 21196558
TI  - The combined effect of parathyroid hormone and bone graft on implant fixation.
AB  - Impaction allograft is an established method of securing initial stability of an
      implant in arthroplasty. Subsequent bone integration can be prolonged, and the
      volume of allograft may not be maintained. Intermittent administration of
      parathyroid hormone has an anabolic effect on bone and may therefore improve
      integration of an implant. Using a canine implant model we tested the hypothesis
      that administration of parathyroid hormone may improve osseointegration of
      implants surrounded by bone graft. In 20 dogs a cylindrical porous-coated
      titanium alloy implant was inserted into normal cancellous bone in the proximal
      humerus and surrounded by a circumferential gap of 2.5 mm. Morsellised allograft
      was impacted around the implant. Half of the animals were given daily injections
      of human parathyroid hormone (1-34) 5 MUg/kg for four weeks and half received
      control injections. The two groups were compared by mechanical testing and
      histomorphometry. We observed a significant increase in new bone formation within
      the bone graft in the parathyroid hormone group. There were no significant
      differences in the volume of allograft, bone-implant contact or in the mechanical
      parameters. These findings suggest that parathyroid hormone improves new bone
      formation in impacted morsellised allograft around an implant and retains the
      graft volume without significant resorption. Fixation of the implant was neither
      improved nor compromised at the final follow-up of four weeks.

PMID- 21196560
TI  - Invited commentary.

PMID- 21196561
TI  - Invited commentary.

PMID- 21196562
TI  - Patient to nurse ratio and risk of ventilator-associated pneumonia in critically
      ill patients.
AB  - OBJECTIVE: To determine how the patient to nurse ratio affects risk for
      ventilator-associated pneumonia. METHODS: Data from an earlier study in 27
      intensive care units in 9 European countries were examined in a secondary
      analysis. The initial cohort included 2585 consecutive patients who had
      mechanical ventilation (1) after admission for treatment of pneumonia or (2) for
      more than 48 hours irrespective of the diagnosis at admission. In units with
      variable staffing levels, the highest patient to nurse ratio in a 24-hour period
      was considered. Patients from 6 units that did not provide data on nurse staffing
      levels were excluded from the analysis. RESULTS: Ventilator-associated pneumonia
      developed in 393 of the 1658 patients (23.7%) in the secondary cohort. In units
      with patient to nurse ratios of 1 to 1, 2 to 1, 2.5 to 1, and 3 to 1, rates were
      9.3%, 25.7%, 18.7%, and 24.2%, respectively (P = .003). Rates were significantly
      lower (P = .002) in units with a ratio of 1 to 1 (9.3%) than in units with a
      ratio of more than 1 patient to 1 nurse (24.4%). After adjustments for
      confounding covariates, ratios of more than 1 patient to 1 nurse were no longer
      associated with increased risk for ventilator-associated pneumonia. CONCLUSIONS:
      A patient to nurse ratio of 1 to 1 appears to be associated with a lower risk for
      ventilator-associated pneumonia, but after adjustments for confounding
      covariates, the difference is not significant.

PMID- 21196563
TI  - International perspectives on the influence of structure and process of weaning
      from mechanical ventilation.
AB  - BACKGROUND: Recently, clinical and research attention has been focused on
      refining weaning processes to improve outcomes for critically ill patients who
      require mechanical ventilation. One such process, use of a weaning protocol, has
      yielded conflicting results, arguably because of the influence of existing
      context and processes. OBJECTIVE: To compare international data to assess
      differences in context and processes in intensive care units that could influence
      weaning. METHODS: Review of existing national data on provision of care for
      critically ill patients, including structure, staffing, skill mix, education,
      roles, and responsibilities for weaning in intensive care units of selected
      countries. RESULTS: Australia, New Zealand, Denmark, Norway, Sweden, and the
      United Kingdom showed similarities in critical care provision, structure, skill
      mix, and staffing ratios in intensive care units. Weaning in these countries is
      generally a collaborative process between nurses and physicians. Notable
      differences in intensive care units in the United States were the frequent use of
      an open structure and inclusion of respiratory therapists on the intensive care
      unit's health care team. Nurses may be excluded from direct management of
      ventilator weaning in some institutions, as this role is primarily assumed by
      respiratory therapists guided by medical directives. Availability of critical
      care beds was highest in the United States and lowest in the United Kingdom.
      CONCLUSION: Context and processes of care that could influence ventilator weaning
      outcomes varied considerably across countries. Further quantification of these
      contextual influences should be considered when translating research findings
      into local clinical practice and when designing randomized controlled trials.

PMID- 21196564
TI  - Optimizing seating in the intensive care unit for patients with impaired
      mobility.
AB  - BACKGROUND: Having intensive care patients sit out of bed improves their
      respiration and psyche and reduces complications of immobilization. OBJECTIVES:
      To compare seating interface pressures to determine a preferred seating surface
      for patients sitting out of bed. METHOD: The study was conducted in 2 phases
      among intensive care patients with impaired mobility who could sit out of bed.
      Pressure mapping was used to test seating surfaces in a non-randomized crossover
      design. In phase 1, three surfaces were compared: (1) regular chair (TotaLift
      II), (2) regular chair with gel overlay, and (3) alternative chair (Hausted APC).
      A new surface, informed from phase 1, was designed and compared with the regular
      chair surface in phase 2. The number of cells recording pressures of 200 mm Hg or
      higher (excessive pressure) for 30 minutes was compared between surfaces.
      RESULTS: In phase 1, the alternative chair had fewer excessive pressures than did
      the regular chair in 67% of seating episodes among 18 patients (P < .001), but
      the alternative chair lacked practical utility. In phase 2, the new seating
      surface was compared with the regular surface using the regular chair frame for
      20 patients. Among patients with excessive pressures, most (93%) had fewer
      excessive pressures recorded on the new surface than on the regular surface (P <
      .001). CONCLUSION: Results from this study provided important data for
      development of a new seating surface for intensive care patients sitting out of
      bed. The new surface promotes patients' comfort and probably reduces risk of
      pressure ulcers.

PMID- 21196565
TI  - Adventures in Neverland: challenges and alternatives.

PMID- 21196568
TI  - Caring for caregivers of the chronically critically ill.

PMID- 21196567
TI  - Caregivers of the chronically critically ill after discharge from the intensive
      care unit: six months' experience.
AB  - BACKGROUND: Chronically critically ill patients typically undergo an extended
      recovery after discharge from the intensive care unit, making involvement of
      family caregivers essential. Prior studies provide limited detail about specific
      ways this experience affects caregivers. OBJECTIVES: To (1) describe lifestyle
      restrictions and distress among caregivers of chronically critically ill patients
      1 and 6 months after discharge and (2) explore how caregivers' lifestyle
      restrictions and distress differ according to patients' and caregivers'
      characteristics. METHODS: Sixty-nine chronically critically ill patients and
      their family caregivers completed follow-up at 1 and 6 months after discharge
      from the intensive care unit. Data were collected from medical records and survey
      via telephone or mail. RESULTS: Caregivers' perceived lifestyle restrictions
      (Changes in Role Function) decreased from 1 month (mean [SD], 23.0 [8.3]) to 6
      months (19.4 [8.6]) after discharge (P = .003), although patients' problem
      behaviors and caregivers' distress (8.9 [9.3] vs 7.9 [9.6], respectively; P =
      .32) did not change. Change in caregivers' lifestyle restrictions differed by
      patients' disposition (P = .02) and functional status (Health Assessment
      Questionnaire; P = .007). Caregiver's lifestyle restrictions remained high when
      patients never returned home or never recovered their preadmission functional
      status. Caregivers reported the most restrictions in social life and personal
      recreation. Patients' negative emotions and pain caused the most caregiver
      distress. CONCLUSIONS: Caregivers of chronically critically ill patients
      perceived fewer lifestyle restrictions over time but reported no change in
      patients' problem behaviors or distress. Lifestyle restrictions and distress
      remained high when patients never returned home or regained their preadmission
      functional status.

PMID- 21196569
TI  - Protecting fragile skin: nursing interventions to decrease development of
      pressure ulcers in pediatric intensive care.
AB  - BACKGROUND: The reported incidence of pressure ulcers in critically ill infants
      and children is 18% to 27%. Patients at risk for pressure ulcers and nursing
      interventions to prevent the development of the ulcers have not been established.
      OBJECTIVES: To determine the incidence of pressure ulcers in critically ill
      children, to compare the characteristics of patients in whom pressure ulcers do
      and do not develop, and to identify prevention strategies associated with less
      frequent development of pressure ulcers. METHODS: Characteristics of 5346
      patients in pediatric intensive care units in whom pressure ulcers did and did
      not develop were compared. Multiple logistic regression was used to determine
      which prevention strategies were associated with less frequent development of
      pressure ulcers. RESULTS: The overall incidence of pressure ulcers was 10.2%.
      Patients at greatest risk were those who were more than 2 years old; who were in
      the intensive care unit 4 days or longer; or who required mechanical ventilation,
      noninvasive ventilation, or extracorporeal membrane oxygenation. Strategies
      associated with less frequent development of pressure ulcers included use of
      specialty beds, egg crates, foam overlays, gel pads, dry-weave diapers, urinary
      catheters, disposable under-pads, body lotion, nutrition consultations, change in
      body position every 2 to 4 hours, blanket rolls, foam wedges, pillows, and draw
      sheets. CONCLUSIONS: The overall incidence of pressure ulcers among critically
      ill infants and children is greater than 10%. Nursing interventions play an
      important role in the prevention of pressure ulcers.

PMID- 21196570
TI  - Medication errors in critically ill adults: a review of direct observation
      evidence.
AB  - OBJECTIVE: To systematically review clinical evidence gathered by direct
      observation of medication errors in adult patients in intensive care units.
      METHODS: Articles published between 1985 and 2008 in English-language journals
      indexed by the Cumulative Index for Nursing and Allied Health Literature and
      PUBMED were searched for studies on medication errors made by intensive care unit
      nurses. Studies in which errors were detected via direct observation were
      included. RESULTS: Six studies met the inclusion criteria, and error incidence
      varied considerably among them. Wrong dose, wrong administration time and rate,
      and dose omission were the most common errors. Antibiotics, electrolytes, and
      cardiovascular drugs were commonly associated with errors, but the evidence about
      factors contributing to errors was inconclusive. Increased monitoring was the
      most common consequence of medication errors, whereas life-threatening and fatal
      adverse events were rare. CONCLUSIONS: Identification of patterns and
      characteristics of medication errors can guide preventive interventions. Factors
      contributing to errors, as well as drugs and error types associated with severe
      adverse events, deserve further investigation.

PMID- 21196571
TI  - General prognostic scores in outcome prediction for cancer patients admitted to
      the intensive care unit.
AB  - BACKGROUND: Intensivists and nursing staff are often reluctant to admit patients
      with cancer to the intensive care unit even though these patients' survival rate
      has improved since the 1980s. OBJECTIVE: To identify factors associated with
      mortality in cancer patients admitted to the intensive care unit and to assess
      and compare the effectiveness of 3 general prognostic models: the Acute
      Physiology and Chronic Health Evaluation (APACHE) II, the Simplified Acute
      Physiology Score (SAPS II), and the Sequential Organ Failure Assessment (SOFA).
      METHODS: A prospective observational cohort study was performed in 2 general
      intensive care units. Discrimination was assessed by using area under the
      receiver operating characteristic curves, and calibration was evaluated by using
      Hosmer-Lemeshow goodness-of-fit tests. RESULTS: A total of 126 patients were
      included during a 3-year period. The observed mortality was 46.8%. All 3 general
      models showed excellent discrimination (area under the curve >0.8) and good
      calibration (P = .17, .14, and .22 for APACHE II, SAPS II, and SOFA,
      respectively). However, discrimination was significantly better with APACHE II
      scores than with SOFA scores (P = .02). Multivariate analyses indicated that
      independent of the 3 severity-of-illness scores, unfavorable risk factors for
      mortality included a patient's preadmission performance status, source of
      admission (internal medicine vs surgery department), and the presence of septic
      shock, infection, or anemia. Combining SOFA and SAPS II scores with these
      variables created prognostic models with improved calibration and discrimination.
      CONCLUSIONS: The general prognostic models seem fairly accurate in the prediction
      of mortality in critically ill cancer patients in the intensive care unit.

PMID- 21196572
TI  - Discordant T waves.

PMID- 21196575
TI  - Globalized pediatric research.

PMID- 21196576
TI  - The globalization of pediatric trials: should we be worried?

PMID- 21196577
TI  - Quantitative mapping of reversible mitochondrial Complex I cysteine oxidation in
      a Parkinson disease mouse model.
AB  - Differential cysteine oxidation within mitochondrial Complex I has been
      quantified in an in vivo oxidative stress model of Parkinson disease. We
      developed a strategy that incorporates rapid and efficient immunoaffinity
      purification of Complex I followed by differential alkylation and quantitative
      detection using sensitive mass spectrometry techniques. This method allowed us to
      quantify the reversible cysteine oxidation status of 34 distinct cysteine
      residues out of a total 130 present in murine Complex I. Six Complex I cysteine
      residues were found to display an increase in oxidation relative to controls in
      brains from mice undergoing in vivo glutathione depletion. Three of these
      residues were found to reside within iron-sulfur clusters of Complex I,
      suggesting that their redox state may affect electron transport function.

PMID- 21196578
TI  - FoxO1 and SIRT1 regulate beta-cell responses to nitric oxide.
AB  - For many cell types, including pancreatic beta-cells, nitric oxide is a mediator
      of cell death; paradoxically, nitric oxide can also activate pathways that
      promote the repair of cellular damage. In this report, a role for FoxO1-dependent
      transcriptional activation and its regulation by SIRT1 in determining the
      cellular response to nitric oxide is provided. In response to nitric oxide, FoxO1
      translocates from the cytoplasm to the nucleus and stimulates the expression of
      the DNA repair gene GADD45alpha, resulting in FoxO1-dependent DNA repair. FoxO1
      dependent gene expression appears to be regulated by the NAD(+)-dependent
      deacetylase SIRT1. In response to SIRT1 inhibitors, the FoxO1-dependent
      protective actions of nitric oxide (GADD45alpha expression and DNA repair) are
      attenuated, and FoxO1 activates a proapoptotic program that includes PUMA (p53-up
      regulated mediator of apoptosis) mRNA accumulation and caspase-3 cleavage. These
      findings support primary roles for FoxO1 and SIRT1 in regulating the cellular
      responses of beta-cells to nitric oxide.

PMID- 21196580
TI  - A more rapid publication process.

PMID- 21196581
TI  - Instruments to measure disease activity in systemic lupus erythematosus -- is our
      net tight enough to catch the hydra?

PMID- 21196579
TI  - Triacylglycerol accumulation activates the mitochondrial apoptosis pathway in
      macrophages.
AB  - Programmed cell death of lipid-laden macrophages is a prominent feature of
      atherosclerotic lesions and mostly ascribed to accumulation of excess
      intracellular cholesterol. The present in vitro study investigated whether
      intracellular triacylglycerol (TG) accumulation could activate a similar
      apoptotic response in macrophages. To address this question, we utilized
      peritoneal macrophages isolated from mice lacking adipose triglyceride lipase
      (ATGL), the major enzyme responsible for TG hydrolysis in multiple tissues. In
      Atgl(-/-) macrophages, we observed elevated levels of cytosolic Ca(2+) and
      reactive oxygen species, stimulated cytochrome c release, and nuclear
      localization of apoptosis-inducing factor. Fragmented mitochondria prior to cell
      death were indicative of the mitochondrial apoptosis pathway being triggered as a
      consequence of defective lipolysis. Other typical markers of apoptosis, such as
      externalization of phosphatidylserine in the plasma membrane, caspase 3 and
      poly(ADP-ribose) polymerase cleavage, were increased in Atgl(-/-) macrophages. An
      artificial increase of cellular TG levels by incubating wild-type macrophages
      with very low density lipoprotein closely mimicked the apoptotic phenotype
      observed in Atgl(-/-) macrophages. Results obtained during the present study
      define a novel pathway linking intracellular TG accumulation to mitochondrial
      dysfunction and programmed cell death in macrophages.

PMID- 21196582
TI  - A ray of hope for tender joints: vitamin D and rheumatoid arthritis.

PMID- 21196583
TI  - High burden of rheumatic disease in Mexico: a comprehensive community-based
      epidemiological study.

PMID- 21196584
TI  - Acute presentation of arthritis mutilans.

PMID- 21196585
TI  - Use of adalimumab in treatment of autoimmune sensorineural hearing loss: a word
      of caution.

PMID- 21196586
TI  - Lack of association of TYK2 gene polymorphisms in Chinese patients with systemic
      lupus erythematosus.

PMID- 21196587
TI  - Tuberculosis screening before biologics -- T-SPOT for all?

PMID- 21196588
TI  - Combination therapy of abatacept and anakinra in children with refractory
      systemic juvenile idiopathic arthritis: a retrospective case series.

PMID- 21196589
TI  - Reactivation of hepatitis B virus after steroid treatment in rheumatic diseases.

PMID- 21196590
TI  - Indigenous Lyme disease in Quebec.

PMID- 21196591
TI  - Towards elucidation of the epidemiology of the rheumatic diseases in Mexico.
      COPCORD studies in the community.

PMID- 21196592
TI  - Epidemiology of the rheumatic diseases in Mexico. A study of 5 regions based on
      the COPCORD methodology.
AB  - OBJECTIVE: To estimate the prevalence of musculoskeletal (MSK) disorders and to
      describe predicting variables associated with rheumatic diseases in 5 regions of
      Mexico. METHODS: This was a cross-sectional, community-based study performed in 5
      regions in Mexico. The methodology followed the guidelines proposed by the
      Community Oriented Program for the Control of the Rheumatic Diseases (COPCORD). A
      standardized methodology was used at all sites, with trained personnel following
      a common protocol of interviewing adult subjects in their household. A "positive
      case" was defined as an individual with nontraumatic MSK pain of > 1 on a visual
      analog pain scale (0 to 10) during the last 7 days. All positive cases were
      referred to internists or rheumatologists for further clinical evaluation,
      diagnosis, and proper treatment. RESULTS: The study included 19,213 individuals;
      11,602 (68.8%) were female, and their mean age was 42.8 (SD 17.9) years. The
      prevalence of MSK pain was 25.5%, but significant variations (7.1% to 43.5%)
      across geographical regions occurred. The prevalence of osteoarthritis was 10.5%,
      back pain 5.8%, rheumatic regional pain syndromes 3.8%, rheumatoid arthritis
      1.6%, fibromyalgia 0.7%, and gout 0.3%. The prevalence of MSK manifestations was
      associated with older age and female gender. CONCLUSION: The prevalence of MSK
      pain in our study was 25.5%. Geographic variations in the prevalence of MSK pain
      and specific diagnoses suggested a role for geographic factors in the prevalence
      of rheumatic diseases.

PMID- 21196593
TI  - Epidemiology of rheumatic diseases. A community-based study in urban and rural
      populations in the state of Nuevo Leon, Mexico.
AB  - OBJECTIVE: To estimate the prevalence of rheumatic diseases in rural and urban
      populations using the WHO-ILAR COPCORD questionnaire. METHODS: We conducted a
      cross-sectional home survey in subjects > 18 years of age in the Mexican state of
      Nuevo Leon. Results were validated locally against physical examination in
      positive cases according to an operational definition by 2 rheumatologists. We
      used a random, balanced, and stratified sample by region of representative
      subjects. RESULTS: We surveyed 4713 individuals with a mean age of 43.6 years (SD
      17.3); 55.9% were women and 87.1% were from urban areas. Excluding trauma, 1278
      individuals (27.1%, 95% CI 25.8%-28.4%) reported musculoskeletal pain in the last
      7 days; the prevalence of this variable was almost twice as frequent in women
      (33% vs 17% in men); 529 (11.2%) had pain associated with trauma. The global
      prevalence of pain was 38.3%. Mean pain score was 2.4 (SD 3.4) on a pain scale of
      0-10. Most subjects classified as positive according to case definition (99%)
      were evaluated by a rheumatologist. Main diagnoses were osteoarthritis in 17.3%
      (95% CI 16.2-18.4), back pain in 9.8% (95% CI 9.0-10.7), undifferentiated
      arthritis in 2.4% (95% CI 2.0-2.9), rheumatoid arthritis in 0.4% (95% CI 0.2
      0.6), fibromyalgia in 0.8% (95% CI 0.6-1.1), and gout in 0.3% (95% CI 0.1-0.5).
      CONCLUSION: This is the first regional COPCORD study in Mexico performed with a
      systematic sampling, showing a high prevalence of pain. COPCORD is a useful tool
      for the early detection of rheumatic diseases as well as for accurately referring
      patients to different medical care centers and to reduce underreporting of
      rheumatic diseases.

PMID- 21196594
TI  - Prevalence of rheumatic regional pain syndromes in adults from Mexico: a
      community survey using COPCORD for screening and syndrome-specific diagnostic
      criteria.
AB  - OBJECTIVE: To assess the prevalence of rheumatic regional pain syndromes (RRPS)
      in 3 geographical areas of Mexico using the Community Oriented Program in the
      Rheumatic Diseases (COPCORD) screening methodology and validate by expert
      consensus on case-based definitions. METHODS: By means of an address-based sample
      generated through a multistage, stratified, randomized method, a cross-sectional
      survey was performed on adult residents (n = 12,686; age 43.6 +/- 17.3 yrs; women
      61.9%) of the states of Nuevo Leon, Yucatan, and Mexico City. Diagnostic criteria
      for specific upper (Southampton group criteria) and lower limb (ad hoc expert
      consensus) RRPS were applied to all subjects with limb pain as detected by
      COPCORD questionnaire. RESULTS: The overall prevalence of RRPS was 5.0% (95% CI
      4.7-5.4). The most frequent syndrome was rotator cuff tendinopathy (2.36%);
      followed by inferior heel pain (0.64%); lateral epicondylalgia (0.63%); medial
      epicondylalgia (0.52%); trigger finger (0.42%); carpal tunnel syndrome (0.36%);
      anserine bursitis (0.34%); de Quervain's tendinopathy (0.30%); shoulder bicipital
      tendinopathy (0.27%); trochanteric syndrome (0.11%); and Achilles tendinopathy
      (0.10%). There were anatomic regional variations in the prevalence of limb pain:
      Yucatan 3.1% (95% CI 2.5-3.6); Nuevo Leon 7.0% (95% CI 6.3-7.7); and Mexico City
      10.8% (95% CI 9.8-11.8). Similarly, the prevalence of RRPS showed marked
      geographical variation: Yucatan 2.3% (95% CI 1.8-2.8); Nuevo Leon 5.6% (95% CI
      5.0-6.3); and Mexico City 6.9% (95% CI 6.2-7.7). CONCLUSION: The overall
      prevalence of RRPS in Mexico was 5.0%. Geographical variations raise the
      possibility that the prevalence of RRPS is influenced by socioeconomic, ethnic,
      or demographic factors.

PMID- 21196595
TI  - Prevalence of musculoskeletal pain and rheumatic diseases in the southeastern
      region of Mexico. A COPCORD-based community survey.
AB  - OBJECTIVE: To assess the prevalence of musculoskeletal (MSK) pain and rheumatic
      diseases in the southeastern Mexican state of Yucatan. METHODS: Using the
      Community Oriented Program in the Rheumatic Diseases (COPCORD) methodology, we
      performed a door-to-door, cross-sectional study generated through a multistage,
      stratified, randomized method on 3915 adult residents (age 42.7 +/- 17.1 yrs;
      women 61.8%; urban setting 45.7%) of the Mexican state of Yucatan. We used
      universally accepted criteria for the diagnosis or classification of rheumatoid
      arthritis (RA), osteoarthritis (OA; knee and hand), fibromyalgia, systemic lupus
      erythematosus (SLE), gout, ankylosing spondylitis, regional rheumatic pain
      syndromes, and inflammatory back pain. RESULTS: Nontraumatic MSK pain in the last
      7 days was present in 766 (19.6%; 95% CI 18.3-20.8) individuals. MSK pain was
      more prevalent in women (26.6%) versus men (12.2%; p < 0.01). Self-reported MSK
      disability occurred in 1.7%. Most MSK pain-related variables were consistently
      more prevalent in the urban setting. The prevalence of rheumatic disease was: OA
      6.8% (95% CI 6.0-7.6); back pain 3.8% (95% CI 3.2-4.4); RA 2.8% (95% CI 2.2-3.3);
      rheumatic regional pain syndromes 2.3% (95% CI 1.9-2.8); inflammatory back pain
      0.7% (95% CI 0.5-1.0); fibromyalgia 0.2% (95% CI 0.1-0.4); gout 0.1% (95% CI 0.07
      0.3); and SLE 0.07% (95% CI 0.01-0.2). CONCLUSION: The prevalence of MSK pain was
      19.6%. MSK pain was more prevalent in women and in the urban setting. A
      remarkably high prevalence of RA was found in this population, which suggests a
      role for geographic factors.

PMID- 21196596
TI  - Prevalence of back pain in the community. A COPCORD-based study in the Mexican
      population.
AB  - OBJECTIVE: Back pain (BP) is frequent in the community; its prevalence in Mexico
      is 6%. Our objective was to determine the prevalence of BP in Mexican communities
      and determine its most important characteristics. METHODS: A cross-sectional
      study of individuals aged > 18 years was conducted in Mexico City and in urban
      communities in the state of Nuevo Leon. Sampling in Mexico City was based on
      community census and in Nuevo Leon, on stratified, balanced, and random sampling.
      Procedures included a door-to-door survey, using the Community Oriented Program
      for the Control of Rheumatic Diseases, to identify individuals with BP > 1 on a
      visual analog scale in the last 7 days. General practitioners/rheumatology
      fellows confirmed and characterized BP symptoms. RESULTS: In all, 8159
      individuals (mean age 43.7 yrs, two-thirds female) were surveyed and 1219 had BP.
      The prevalence of nontraumatic BP in the last 7 days was 8.0% (95% CI 7.5-8.7).
      The mean age of these individuals was 42.7 years, and 61.9% were female. Thirty
      seven percent had inflammatory BP [prevalence of 3.0% (95% CI 2.7-3.4)]. Compared
      with the state of Nuevo Leon, the characteristics and consequences of BP in
      Mexico City were more severe. In logistic regression analysis, living in Mexico
      City, having a paid job, any kind of musculoskeletal pain, high pain intensity,
      and obesity among other variables were associated with BP. CONCLUSION: The
      prevalence of nontraumatic BP in the last 7 days in urban communities in Mexico
      is 8.0%. However, clinical features and consequences differed among the
      communities studied, suggesting a role for local factors in BP.

PMID- 21196597
TI  - Validity of the COPCORD core questionnaire as a classification tool for rheumatic
      diseases.
AB  - OBJECTIVE: Rheumatic diseases are vastly underdiagnosed and undertreated,
      particularly among minorities and those of low socioeconomic status. The WHO-ILAR
      Community Oriented Program in the Rheumatic Diseases (COPCORD) advocates
      screening of musculoskeletal complaints in the community. The objective of this
      study was to evaluate the performance of the COPCORD Core Questionnaire (CCQ) as
      a diagnostic tool for rheumatic diseases. METHODS: We conducted a cross-sectional
      study designed in parallel with a large COPCORD survey in Mexico. A subsample of
      17,566 questionnaires, selected from 4 of the 5 states included in a national
      COPCORD survey were included in the analysis as a diagnostic test to evaluate
      sensitivity, specificity, receiver operating characteristics curve (ROC), and
      positive likelihood ratio (LR+) of the CCQ as a case-detection tool for rheumatic
      diagnosis and for the most frequent diagnoses identified in the survey,
      osteoarthritis, regional rheumatic pain syndromes, and rheumatoid arthritis (RA).
      Logistic regression with the questions with LR+ >= 1 was performed to identify
      the strength of association (OR) for each question. RESULTS: Pain in the last 7
      days, high pain score (> 4), and previous diagnosis were the questions with
      highest LR+ for diagnosis, and for diagnosis of RA treatment with NSAID. The
      variables that contributed most to the model were pain in the last 7 days (OR
      2.0, 95% CI 1.8-2.3), NSAID treatment (OR 3.3, 95% CI 3.0-3.7), a high pain score
      (OR 1.15, 95% CI 1.13-1.17), and having a previous diagnosis (OR 1.4, 95% CI 1.3
      1.6). These 4 questions had R(2) = 0.24, p < 0.01, for detection of any rheumatic
      diagnosis. The single variable that explains 16% (OR 1.33, 95% CI 1.31-134) of
      variance was a high pain score in the last 7 days. CONCLUSION: Some variables
      were identified in the CCQ that could be combined in a brief version for case
      detection of rheumatic diseases in community surveys. The validity of this
      proposal has to be tested against the original version.

PMID- 21196598
TI  - The fatal flaw: what it is and how to avoid it.

PMID- 21196600
TI  - MRI of the Flow-SecureTM urinary sphincter.

PMID- 21196601
TI  - Giant terminal hydronephrosis.

PMID- 21196599
TI  - Reconstitution of proapoptotic BAK function in liposomes reveals a dual role for
      mitochondrial lipids in the BAK-driven membrane permeabilization process.
AB  - BAK is a key effector of mitochondrial outer membrane permeabilization (MOMP)
      whose molecular mechanism of action remains to be fully dissected in intact
      cells, mainly due to the inherent complexity of the intracellular apoptotic
      machinery. Here we show that the core features of the BAK-driven MOMP pathway can
      be reproduced in a highly simplified in vitro system consisting of recombinant
      human BAK lacking the carboxyl-terminal 21 residues (BAKDeltaC) and tBID in
      combination with liposomes bearing an appropriate lipid environment. Using this
      minimalist reconstituted system we established that tBID suffices to trigger
      BAKDeltaC membrane insertion, oligomerization, and pore formation. Furthermore,
      we demonstrate that tBID-activated BAKDeltaC permeabilizes the membrane by
      forming structurally dynamic pores rather than a large proteinaceous channel of
      fixed size. We also identified two distinct roles played by mitochondrial lipids
      along the molecular pathway of BAKDeltaC-induced membrane permeabilization.
      First, using several independent approaches, we showed that cardiolipin directly
      interacts with BAKDeltaC, leading to a localized structural rearrangement in the
      protein that "primes" BAKDeltaC for interaction with tBID. Second, we provide
      evidence that selected curvature-inducing lipids present in mitochondrial
      membranes specifically modulate the energetic expenditure required to create the
      BAKDeltaC pore. Collectively, our results support the notion that BAK functions
      as a direct effector of MOMP akin to BAX and also adds significantly to the
      growing evidence indicating that mitochondrial membrane lipids are actively
      implicated in BCL-2 protein family function.

PMID- 21196602
TI  - Genital avulsion.

PMID- 21196604
TI  - Enlightened physicians: setting out on an elite academic career in the second
      half of the eighteenth century.
AB  - In the second half of the eighteenth century, medical doctors faced heavy
      competition. They competed for patients and for institutional positions and
      sought a variety of means to enhance their reputations. Among rank-and-file
      physicians, some strove to respond to the high expectations and rational
      discourse fueled by Enlightenment philosophy. They aimed to build a new medicine
      on rational and empirical principals. Concentrating on the rich correspondence
      left by young physicians born in Geneva, this article maps out the social and
      moral dilemmas encountered by ambitious young physicians in the second half of
      the eighteenth century, who, like many thousands of others, flocked to Edinburgh,
      "the first medical school" in Europe. Conscious that they formed but one group
      among a series of possible practitioners, they pondered over cultural codes,
      civilities and economic realities as they strove to promote the figure of a
      knowledgeable, experienced, gentlemanlike physician.

PMID- 21196603
TI  - The risks of childbirth: physicians, finance, and women's deaths in the law
      courts of seventeenth-century Rome.
AB  - In seventeenth-century Rome a popular financial scheme made it crucial to
      establish if pregnancy or childbirth had caused a woman's death. Courts sought
      medical advice, and this prompted physicians to reconsider the issues. Their
      disagreements provide historians with evidence from which to reassess received
      views of early modern doctors' involvement with birthing bodies. Among others,
      Paolo Zacchia intervened, revealing discord between physicians and jurists on how
      to establish the causes of death. One of his testimonies in a case shows more
      broadly how legal, medical, and lay views on pregnancy and childbirth intersected
      in courts of law. In Roman tribunals the very distinction between healthy and
      preternatural births was contentious, and the parties had an interest in having
      births either proved healthy in medical terms or construed as pathological. The
      controversies, the author argues, challenge historical expectations about early
      modern perceptions, including the boundaries between female and male, private and
      public, healthy and pathological.

PMID- 21196605
TI  - "War dysentery" and the limitations of German military hygiene during World War
      I.
AB  - This article examines major epidemics of bacillary dysentery in the German army
      as well as among civilians in eastern Europe and in Germany during World War I.
      These epidemics were all the more surprising in light of prewar advances in
      understanding the disease and limiting dysentery outbreaks. Three major reasons
      are adduced for the incapacity of German military hygienists to prevent wartime
      epidemics. First was the difficulty of bacteriological testing at the front,
      especially early in the war, with negative consequences for diagnosis, therapy,
      and disease control. Second was inadequate hygiene including major shortcomings
      in latrine cleanliness and attempts to grapple with the "fly plague." Third was
      the lack of a Pasteur-type vaccine until late in the war. Susceptibility to
      dysentery was also heightened by war-related nutritional deficiencies. Taking off
      from an article by the English medical historian Roger Cooter, this article shows
      that the concept of "war dysentery" was socially constructed and served a variety
      of professional interests but at the same time takes issue with Cooter's
      arguments against linking "war" and "epidemics" pathogenetically.

PMID- 21196606
TI  - Spaced-out in Saskatchewan: modernism, anti-psychiatry, and
      deinstitutionalization, 1950-1968.
AB  - On the eve of deinstitutionalization, a group of professionals, including an
      architect, a psychiatrist, and a psychologist, joined together in pursuit of a
      middle ground between outright closure of long-stay hospitals and the
      introduction of out-patient services in general hospitals. Augmented by the use
      of the hallucinogenic drug LSD, these men produced a trenchant critique of modern
      psychiatry and the changing mental health system without subscribing to
      antipsychiatry. Caught among shifting psychiatric paradigms, fiscal constraints,
      and political pressure to situate mental health within an encroaching system of
      publicly funded health care reforms, their proposed mental hospital designs
      failed to stem the tidal wave of post-World War II changes in mental health care.

PMID- 21196607
TI  - Epidemiology of hepatitis C in the Middle East.
AB  - The epidemiology of hepatitis C virus (HCV) infection is not well defined in the
      Middle East region. A review of the epidemiology and modes of transmission and
      spread of HCV infection in regions located in the Middle East, including Iran,
      Bahrain, Iraq, Oman, Qatar, Jordan, Kuwait, Saudi Arabia, United Arab Emirates,
      Cyprus, Sudan, Egypt, Pakistan, Syria, Turkey, Lebanon, Gaza Strip and West Bank,
      and Yemen, was undertaken. Public health strategies, well-programmed, population
      based and certain HCV infection at-risk surveys, and transmission risk factors'
      settings detection are insufficient in some countries of this region. Since
      significant differences in prevalence and epidemiology of HCV exist among the
      Middle East countries or even inside the countries, control strategies should
      take these differences into account.

PMID- 21196608
TI  - The treatment of relapse in adults with minimal change nephrotic syndrome: myths
      and facts.
AB  - Few controlled trials have studied the treatment of relapse in adults with
      minimal change disease. Repeated courses of steroids, cyclophosphamide,
      cyclosporine and even mycophenolate mofetil (MMF), all seem to play a role. The
      aim of this study was to review and critically analyze the literature regarding
      the use of immunosuppressive therapy for the treatment of relapse in adults with
      minimal change nephrotic syndrome (MCNS). An intensive search was done for
      published trials in the general medical database. Retrieved studies were further
      sorted according to specific inclusion and exclusion criteria. Selected trials
      were critically analyzed and evaluated using the Oxford Centre for Evidence-based
      Medicine Levels of Evidence, 2009 rating. Six studies were selected and
      systematically reviewed. One randomized controlled trial compared the use of
      cyclo-phosphamide versus cyclosporine (11 adults) and showed that both drugs are
      effective in the treatment of frequent relapses [level 1b evidence (grade B)].
      Three trials (total of 20 patients) tested the use of cyclosporine therapy and
      showed that cyclosporine, though effective in the treatment of relapse, is
      associated with an extremely high incidence of subsequent relapses following drug
      with-drawal. A long-term follow-up cross-sectional study of 95 patients, with 69
      relapsers, supported the use of steroids in the treatment of occasional relapses
      [level 2c evidence (grade C)]. One case series described the benefits of MMF
      [level 4 evidence (grade C)]. Most of the the clinical trials studied were
      heterogeneous, underpowered by small adult populations, open-labelled, non
      randomized, with poor statistical analysis, validity and utility. We conclude
      that there is poor evidence that successful treatment of the first relapse of
      adult MCNS can be achieved with a second course of steroids or cyclosporine.
      Also, there is weak evidence that frequent relapses can be treated using
      cyclophosphamide, cyclosporine or MMF. Powered, multi-centered, randomized,
      blinded, controlled trials, with long-term follow-up are required to know the
      optimal treatment for relapsing adult MCNS.

PMID- 21196609
TI  - Allograft renal rejection and chemokine polymorphism.
AB  - Chemokines play a major role in the process by which leukocytes are recruited
      from the bloodstream into the sites of inflammation. Genes for the chemokine
      receptors CCR5, CCR2 and MCP-1 are characterized by functional polymorphisms
      implicated in transplant rejection. To investigate this association, we analyzed
      polymorphisms of CCR5-?32, CCR5-59029-A/G, CCR2-V64I and MCP-1 G/A (-2518) in 173
      renal transplant recipients and 169 healthy blood donors. The patients were
      classified in two groups: Group-1 (G-1) included 33 HLA-identical recipients and
      Group-2 (G-2) included 140 (one or more) mismatched graft recipients. Forty-two
      patients had developed acute rejection episodes (ARs): seven in G-1 and 35 in G
      2. Thirteen G-2 patients developed chronic allograft dysfunction (CAD). The
      genotypic and allelic frequencies of all polymorphisms studied did not reveal
      significant differences between patients and controls and among G-1 and G-2
      recipients. However, a significant risk of acute renal transplant rejection was
      found in G-1 patients who possessed the CCR2-64I allele (odds ratio 0.24, 95%
      confidence inter-val [CI], 0.05-1.06; P = 0.035). There was no significant
      association of this polymorphism and CAD. In conclusion, the observed association
      of CCR2-64I with AR should be added to the spectrum of immunogenetic factors
      known to be involved in allograft renal loss.

PMID- 21196610
TI  - Three-year post-transplant Medicare payments in kidney transplant recipients:
      associations with pre-transplant comorbidities.
AB  - Little is known about the influence of pre-transplant comorbidities on post
      transplant expenditures. We estimated the associations between pre-transplant
      comorbidities and post-transplant Medicare costs, using several comorbidity
      classification systems. We included recipients of first-kidney deceased donor
      transplants from 1995 through 2002 for whom Medicare was the primary payer for at
      least one year pre-transplant (N = 25,175). We examined pre-transplant
      comorbidities as classified by International Classification of Diseases (ICD-9
      CM) codes from Medicare claims with the Clinical Classifications Software (CCS)
      and Charlson and Elixhauser algorithms. Post-transplant costs were calculated
      from payments on Medicare claims. We developed models considering Organ
      Procurement and Transplantation Network (OPTN) variables plus: 1) CCS categories,
      2) Charlson, 3) Elixhauser, 4) number of Charlson and 5) number of Elixhauser
      comorbidities, independently. We applied a novel regression methodology to
      account for censoring. Costs were estimated at individual and population levels.
      The comorbidities with the largest impact on mean Medicare payments included
      cardiovascular disease, malignancies, cerebrovascular disease, mental conditions
      and functional limitations. Skin ulcers and infections, rheumatic and other
      connective tissue disease and liver disease also contributed to payments and have
      not been considered or described previously. A positive graded relationship was
      found between costs and the number of pre-transplant comorbidities. In
      conclusion, we showed that expansion beyond the usually considered pre-transplant
      comorbidities with inclusion of CCS and Charlson or Elixhauser comorbidities
      increased the knowledge about comorbidities related to augmented Medicare
      payments. Our expanded methodology can be used by others to assess more
      accurately the financial implications of renal transplantation to Medicare and
      individual transplant centers.

PMID- 21196611
TI  - Outcome of patients treated with automated peritoneal dialysis: effects of
      selection of patients.
AB  - To determine the effect of selection of peritoneal dialysis patients who used
      auto-mated PD (APD) as a first renal replacement therapy (RRT) option, we studied
      two groups of adult chronic kidney disease (CKD) patients treated with APD over a
      period of 4 years: group 1 included 30 patients in whom APD was the first choice
      for RRT and group 2 included 40 patients transferred from failed hemodialysis
      (HD) treatment. Both groups were matched for the original causes of CKD and
      comorbid conditions. However, group 1 had significantly higher residual renal
      function (RRF) than group 2 [glomerular filtration rate (GFR) 11.85 +/- 4 mL/min
      and urine output 995 +/- 465 mL/day vs. 3.69 +/- 3.7 mL/min and 340 +/- 447
      mL/day, respectively, P = 0.0001] and Kt/v (2.7 +/- 0.7 vs. 1.9 +/- 0.4,
      respectively, P = 0.006). Most of the patients were compliant with their APD
      prescription, performed ideal PD techniques, achieved adequate dialysis and fluid
      ultra-filtration, and experienced much less than average infectious and non
      infectious complications. However, group 1 achieved better clinical outcome than
      group 2, including relatively higher survival rate and kidney transplantation,
      significantly fewer episodes of peritonitis per year (0.09 vs. 0.14,
      respectively, P = 0.0001), higher serum albumin (2.95 +/- 0.3 vs. 2.7 +/- 0.27
      g/dL, respectively, P = 0.035), hemoglobin (11.5 +/- 0.9 vs. 10.6 +/- 0.7 g/dL,
      respectively, P = 0.022) and lower parathormone levels (283 +/- 117 vs. 389 +/-
      269 pg/mL, respectively, P = 0.02). They also maintained significantly higher
      total fluid removal compared to group 2 (1120 +/- 330 vs. 560 +/- 300 mL/day,
      respectively, P = 0.004), higher RRF (GFR 8 +/- 2.6 mL/min vs. 1.8 +/- 2.4
      mL/min, respectively, P = 0.0001), and urine output (556 +/- 447 mL/day vs. 240
      +/- 347 mL/day, respectively, P = 0.004), and significantly higher Kt/v (2.8 +/-
      0.7 vs. 1.9 +/- 0.4, respectively, P = 0.2). In conclusion, in CKD patients, PD
      is a viable initial modality of RRT, and with better RRF may have a better
      outcome than as a secondary choice.

PMID- 21196612
TI  - Peritoneal membrane characteristics in patients on peritoneal dialysis.
AB  - Peritoneal dialysis (PD) is a well-established modality for treatment of patients
      with end-stage renal disease, giving excellent patient and technique survival
      rates. In Saudi Arabia, data collected by the Saudi Center for Organ
      Transplantation showed that in 2008, patients on PD accounted for a mere 4.8% of
      total patients on renal replacement therapy, including hemodialysis and renal
      transplantation. This study was conducted to identify the characteristics of
      membrane permeability in the Saudi population and to assess the role of various
      factors affecting solute transport across the peritoneal membrane. We followed up
      a total of 52 patients on Continuous Ambulatory Peritoneal Dialysis (CAPD) as
      well as Automated Peritoneal Dialysis (APD), being treated in the PD unit of the
      King Khalid University Hospital, Riyadh. There were 30 female and 22 male
      patients; 14 patients were using CAPD while 38 patients were on APD. The mean age
      of the patients was 50.5 years, with a range of 14-86 years. The average body
      mass index (BMI) was 27.1 kg/m2 and the mean body surface area (BSA) of the study
      patients was 1.71 m2. A standardized PET test was performed on all patients, 4-6
      weeks after initiation of regular PD. The Kt/V and creatinine clearance measured
      6-8 weeks after initiation of dialysis were 1.96 and 56.59 L/week, respectively.
      Residual renal function was assessed on the basis of daily urine output, using 24
      hour urine collection. The mean serum urea con-centration was 16.91 mmol/L and
      mean serum creatinine was 702 MUmol/L. According to the Peritoneal Equilibration
      Test (PET), 8% of the subjects belonged to the high trans-porter category, 44%
      patients belonged to the high-average transport group, 46% to the low-average
      category and 2% came in the low transporter category. Our study suggests that the
      patient characteristics and demographic para-meters seen in the Saudi population
      are comparable to those seen in other studies from the Middle East and worldwide,
      including data collected from Canada, New Zealand and Mexico.

PMID- 21196613
TI  - Can continuous venovenous hemofiltration prevent contrast-agent induced
      nephropathy in patients with advanced chronic kidney disease after coronary
      angiography?
AB  - To determine whether contrast induced nephropathy (CIN) post coronary angio
      graphy procedure can be prevented in chronic kidney disease (CKD) patients by
      continuous venovenous hemofiltration (CVVH), we evaluated 98 CKD patients [52
      (53.1%) were males, the mean age was 60.7 +/- 11.0 years] who underwent coronary
      angiography from January 2004 to December 2006. Serum creatinine (Cr) before the
      procedure was 411 +/- 79.9 MUmol/L and crea-tinine clearance (Cr Cl) was 18.04 +/
      4.26 mL/min. All patients underwent post procedure CVVH for 21.34 +/- 2.12
      hours. The mean time interval between the procedure and the start of CVVH was
      44.3 +/- 18.8 min. The mean serum Cr at discharge was 403 +/- 88.4 MUmol/L (Cr Cl
      18.5 +/- 4.61 mL/min) and was 423 +/- 88.9 MUmol/L (Cr Cl17.6 +/- 4.27 mL/min) 15
      days after the procedure. One patient (1.02%) developed worsening of renal
      functions that required repeated CVVH during hospitalization and ended up on
      regular hemodialysis. There was no in-hospital mortality. We conclude that CVVH
      is effective in preventing CIN after coronary angiography in CKD patients.

PMID- 21196614
TI  - New indicator for prostate gland biopsy when malignancy is in question.
AB  - The aim of our study was to find out a new indicator with a higher specificity
      level than prostate prostate-specific antigen (PSA) in order to achieve a better
      selection of patients who will undergo prostate biopsy. Trans-rectal ultrasound
      guided prostate biopsy was performed in 135 patients who had elevated PSA level
      and/or palpable nodule on digital rectal examination. The PSA level was <= 10
      ng/mL in 81 patients and >10 ng/mL in 54 patients. We designed a new formula
      consisting of prostate volume, patient's age, and free prostate specific antigen.
      Its resultant was defined as prostate biopsy index and was compared with the most
      currently used parameters. Histology results yielded prostate gland malignancy in
      40 (30%) patients. Our new index differed significantly between the malignant and
      the non-malignant patient categories (P = 0.01). The ROC curve analysis at
      different specificity and sensitivity levels (85%, 90% and 95%) and regarding the
      area under the curve (AUC), our new index was significantly better than the other
      studied parameters (P = 0.001). Additionally, the AUC in patients with a PSA
      level <= 10 ng/mL and between 10.1 and 20 ng/mL was 0.75 and 0.78, with a
      sensitivity of 91% and 83% and a specificity of 24% and 73%, respectively, at a
      cut-off point of 1.7. The overall sensitivity and specificity at the same point
      were 80% and 41%, respectively. In conclusion, the performance of our new index
      was superior to all other evaluated parameters. At 83% sensitivity with a cut-off
      point of 1.7, 63.5% of the performed biopsies could have been avoided in patients
      with a PSA level between 10.1 and 20 ng/mL.

PMID- 21196615
TI  - The anomalies associated with congenital solitary functioning kidney in children.
AB  - The aim of this study was to determine the incidence of associated urological and
      non-urological anomalies as well as the renal outcome in patients with a
      congenital solitary func-tioning kidney (CSFK). A retrospective review of 30
      consecutive cases of CSFK seen at the pediatric renal service at the Jordan
      University Hospital between 2004 and 2008 was performed. There were 20 males and
      10 females, whose ages ranged from five days to 14 years. In 20 patients (67%),
      the left kidney was absent. Associated anomalies were detected in 23 (77%) of the
      30 patients; urological anomalies accounted for 47% (14/30) and non-urological
      anomalies were found in 19/30 (53%) patients. The latter included anomalies of
      the ear, nose and throat (ENT) in 9/30 (30%), musculoskeletal system (one with
      hypermobile joints) in 8/30 (27%), gastrointestinal (GI) in 7/30 (23%),
      cardiovascular (CV) in 4/30 (13%) and dermatological with epidermolysis bullosa,
      endocrine (euthyroid goiter) and gynecological (cervical cyst) in one patient
      each (3%). Proteinuria was seen in 6/30 (20%) and hypertension in 2/30 (7%)
      patients. Chronic renal failure (CRF) was seen in 6/30 (20%) patients, of whom
      three had end-stage renal failure (ESRF). CRF was seen mainly in patients with
      more than two associated urological anomalies. Idiopathic hyperuricosuria was
      found in five of the six tested patients (83%). In our study, the most common
      associated anomalies with CSFK were urological. The presence of more than two
      associated urological anomalies increased the risk of CRF.

PMID- 21196616
TI  - Management of ureteral complications in renal transplantation: prevention and
      treatment.
AB  - Urinary anastomotic complications following renal transplantation cause
      significant patient morbidity. In ureteric reconstruction, different techniques
      are used to reduce complications (such as leakage or obstruction). In this study,
      we suggested two aspects of management of the complications of ureteral
      anastamosis: ureteral spatulation more than 10 mm for prevention and percutaneous
      nephrostomy and balloon dilatation as the first steps of treatment. A sequential
      double-blind random trial with 170 kidney transplant recipients was performed,
      dividing the patients into two groups: group 1 patients had ureteral spatulation
      length <= 10 mm (70 recipients) and group 2 patients had ureteral spatulation >=
      10 mm (100 recipients). In patients with ureteral stenosis, percutaneous
      nephrostomy (PCN) and balloon dilatation were used as the first step of
      treatment. The mean age was 44 +/- 4.2 years. Before and after removing the
      double J stent, ureteral complications that needed surgical intervention occurred
      in 16/70 recipients in group 1 (20.3%) and in eight/100 recipients in group 2
      (8%). There is a significant difference between the two groups (P < 0.05). PCN
      and balloon dilatation were performed in 24 patients with ureteral stenosis.
      Eleven patients had a good response and 13 patients underwent surgical procedures
      (in four of theses patients, ileal interposition was used for repairing the
      ureteral defects). In conclusion, ureteral spatulation more than 10 mm in
      prevention of ureteral stenosis and use of PCN and balloon dilatation in the
      first step of treatment of ureteral obstruction should be the management choice
      for these patients.

PMID- 21196617
TI  - Efficacy of low dose spironolactone in chronic kidney disease with resistant
      hypertension.
AB  - To determine the antihypertensive benefit of adding low dose sprinolactone to
      multi-drug regimens that included a diuretic, a calcium channel blocker and
      angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in
      patients with moderately severe chronic kidney disease (CKD) [glomerular
      filtration rate (GFR) 25-50 mL/min] and resistant hyper-tension, we studied 41
      patients randomly divided into two groups: group 1: patients who received placebo
      as spironolactone and group 2: patients who received spironolactone 25-50 mg/day.
      The patients were evaluated during follow-up at the 6th and 12th weeks. The mean
      decrease in systolic and diastolic blood pressure after 6 weeks of spironolactone
      was 33 +/- 8 and 13 +/- 2 mmHg, respectively, and it was maintained after 12
      weeks of spironolactone wherein the values were 36 +/- 10 and 12 +/- 2 mmHg,
      respectively, while there was no change in the blood pressure in the control
      group. Hyperkalemia (serum potassium >5.5 meq/L) occurred in one subject in the
      spironolactone group. We conclude that low-dose spironolactone may provide a
      significant additive blood pressure reduction in CKD patients (stage 2 and 3)
      with resistant hypertension.

PMID- 21196618
TI  - Determination and comparison of mean random urine calcium between children with
      vesicoureteral reflux and those with improved vesicoureteral reflux.
AB  - Urinary reflux can cause irreversible complications such as reflux nephropathy
      and ESRD. Diagnostic imaging such as voiding cystourethrogram (VCUG) is invasive
      and causes irradiation. Several studies have shown that markers such as urine IL
      8 or serum Procalcitonin might be useful for the diagnosis of vesico-ureteral
      reflux (VUR) as a substitution for invasive methods. The aim of this study was to
      determine and compare the mean urine Ca/Cr ratio and hypercalciuria between two
      groups of children aged 2-10 years affected by VUR. This is a cross-sectional
      study in which 32 children having the following entrance criteria were included:
      children 2-10 years old not affected by urinary tract infection during the last
      three months and their reflux or recovery having been diagnosed by VCUG or direct
      radionuclide cystography, divided into two groups of affected by reflux and
      recovered from reflux. Then, the point urine specimens were collected with
      permission of their parents in a single laboratory and urine Ca and Cr for each
      specimen were measured. The Ca/Cr ratio was calculated for each child to evaluate
      Ca excretion from the urine, which was possible without collecting the 24-hours
      urine. The Ca/Cr ratio mean and the hypercalciuria were compared between the
      groups. To analyze our data, the Mann-Whiney test and the Chi-square test were
      used, using SPSS V.15. Thirty-two children, including 18 children recovered from
      reflux and 14 affected by reflux, were entered in our study. The Ca/Cr ratio mean
      was 0.692 +/- 1.874 for the affected and 0.118 +/- 0.187 for the recovered group.
      The Ca/Cr ratio mean for the affected male and female groups was 0.012 +/- 0.008
      and 0.805 +/- 1.0913, respectively. This amount was 0.0175 +/- 0.01767 for the
      recovered male and 0.131 +/- 0.195 for the recovered female group. There was no
      significant statistical difference between the groups with respect to the Ca/Cr
      ratio mean, but there was a significant statistical difference between the two
      groups of females (P-value = 0.026). Also, there was no significant statistical
      difference between the two groups of males relative frequency of hypercalciuria
      was significantly higher in the group affected by reflux than in the recovered
      from reflux group (P-value = 0.017). Urine Ca excretion is elevated in children
      with reflux, and may be more useful as an appropriate marker for the diagnosis of
      VUR than other invasive methods.

PMID- 21196619
TI  - High mortality in critically ill patients infected with 2009 pandemic influenza A
      (H1N1) with pneumonia and acute kidney injury.
AB  - Patients infected with H1N1 virus may develop pneumonia and acute kidney injury
      (AKI). To determine the epidemiological characteristics, clinical features,
      management and out-comes of patients with confirmed H1N1 complicated by pneumonia
      and AKI and treatment with oseltamivir and to identify the prognostic indicators,
      we studied all the patients with a confirmed diagnosis of H1N1 infection with
      pneumonia and AKI, using real-time reverse transcriptase-polymerase chain
      reaction (RT-PCR) assay, between October 2009 and March 2010. H1N1 infection was
      confirmed in 20 patients with pneumonia and AKI; the mean age was 42.8 +/- 18.2
      years and 12 (60%) of the patients were males. Eleven patients were between 15
      and 50 years of age, and 15 had preexisting medical conditions. All patients had
      fever, cough, dyspnea or respiratory distress, increased serum lactate
      dehydrogenase levels, pneumonia and AKI. Fifteen (75%) patients required
      mechanical ventilation and 14 (70%) died. None of the health care workers
      developed influenza-like illness, when they received oseltamivir prophylaxis.
      Mortality was associated with higher Acute Physiology and Chronic Health
      Evaluation (APACHE) II, Sequential Organ Failure Assessment score (SOFA),
      Multiple Organ Dysfunction Score (MODS), XRChest score, in addition to
      requirement of inotrope, ventilator support, renal replacement therapy (RRT), and
      presence of underlying risk factor for severe disease.

PMID- 21196620
TI  - Faculty-led faculty development: evaluation and reflections on a distributed
      educational leadership model.
AB  - This report describes and explores the impact of a series of faculty-led faculty
      development programs underpinned by principles of distributed educational
      leadership. We aimed to prepare faculty for their roles as facilitators and
      assessors in a newly implemented problem-based (PBL) graduate entry medical
      program. We asked participants attending a series of faculty development programs
      to evaluate workshops attended using an in-house designed survey. Overall
      descriptive statistics for all workshops and qualitative feedback for PBL
      workshops alone were examined. It was concluded that clinical faculty who are not
      specialized in medical education can offer high-quality, well-accepted training
      for their peers. Faculty development, underpinned by a distributed leadership
      approach which supports learning organization tenets, imaginative, flexible and
      democratic approaches to developing and nurturing expertise at all levels of the
      organization, is likely to lead to improvements in medical education. Despite the
      limitations of the survey approach to evaluation of faculty development programs,
      the information provided is useful both as a basis for decision making and
      program improvement.

PMID- 21196621
TI  - Endothelial dysfunction and inflammation in different stages of essential
      hypertension.
AB  - The objective of this study was to assess the various factors affecting
      endothelial function in essential hypertensives and to establish a relation
      between them in a regression model. Also, the micro-inflammatory state that is
      known to exist in essential hypertension was evaluated. Sixty newly detected
      patients of essential hypertension not on any prior treatment and classified into
      Stage-1 or Stage-2 hypertension according to the JNC-VII criteria were recruited
      in the study. After a detailed history and physical examination, investigations
      including blood urea, serum creatinine, blood sugar (F), S. lipid profile (F),
      urine for albumin, sugar and sediments, X-ray of the chest, ECG and fundus
      examination were carried out. Urine for microalbuminuria, Hs-CRP and brachial
      artery reactivity were tested as markers of endothelial dysfunction and
      inflammation. The CRP levels, taken as a marker of inflammation in hypertension,
      were significantly elevated in a majority of the study subjects. Endothelial
      dysfunction was significantly more quantified in Stage-2 hypertension as compared
      with Stage-1 hypertension (P < 0.01). The Hs-CRP levels were consistently found
      to be elevated in both the stages of hypertension in our study, with an
      insignificant difference between the two groups. A significant association was
      noted with the stage of hypertension, triglycerides, microalbuminuria, CRP, LDL
      cholesterol and age, with the stage of hypertension emerging as the most powerful
      predictor variable (P < 0.0001) followed closely by microalbuminuria (P < 0.0001)
      in a multiple regression analysis model. The present study reinforces the view
      that hypertension is in part an inflammatory disorder. Endothelial dysfunction is
      an important component of essential hypertension, the severity being determined
      by the stage of hypertension, microalbuminuria, LDL-cholesterol, triglycerides,
      age and Hs-CRP levels independently. The undesirable inflammatory response can be
      cost-effectively prevented at various levels by targeting the potentially
      modifiable risk factors elucidated in the study.

PMID- 21196622
TI  - Post transplantation anemia: re-emphasizing the use of erythropoietin.

PMID- 21196623
TI  - Fulminant hepatitis following primary herpes simplex virus infection.
AB  - Fulminant hepatic failure (FHF) is a rare but well-recognized complication of
      primary herpes simplex virus (HSV) infection in immunocompromised patients. Here,
      we report two cases of acute hepatitis and FHF secondary to primary HSV type 1
      infection following renal transplantation in the absence of any mucocutaneous
      manifestation. High levels of HSV type-1 DNA were detected in the blood. Both
      patients were seronegative for HSV 1 and HSV 2 immunoglobulin G (IgG) before
      transplantation, whereas the donor of patient 1 was HSV 1 IgG-positive but had no
      viremia and the donor of patient 2 was HSV-seronegative. Patient 1 recovered with
      acyclovir and immunoglobulin whereas patient 2 did not respond and succumbed to
      death. HSV-seronegative patients are potentially at risk of developing severe
      primary HSV disease following transplantation, particularly in the absence of
      routine anti-viral prophylaxis. HSV infection should always be excluded in
      transplant patients with hepatic dysfunction.

PMID- 21196624
TI  - Drug interaction between rifampicin and sirolimus in transplant patients.
AB  - We report two cases of drug interaction between rifampicin and sirolimus in renal
      trans-plant patients who were diagnosed with tuberculosis after transplantation
      and induction of immuno-suppressive therapy with sirolimus. The dosage of
      sirolimus had to be increased, in one case up to six-fold and in the second case
      up to five-fold, to maintain serum levels after starting the rifampicin. The two
      patients tolerated the treatment well, with no signs of tuberculosis and good
      renal function.

PMID- 21196625
TI  - A rare association of Castleman's disease and nephrotic syndrome.
AB  - Castleman's Disease (CD) is an uncommon and poorly understood disorder of lymph
      node hyperplasia of unknown etiology. This entity belongs to the atypical
      lymphoproliferative disorders, a heterogeneous group of diseases characterized by
      a hyperplastic reactive process involving the immune system. The association of
      the nephrotic syndrome and CD is extremely rare and their interrelation remains
      enigmatic. We report a case of CD of the hyaline-vascular type with unicentric
      localization complicated by nephrotic syndrome.

PMID- 21196626
TI  - Sarcomatoid renal cell carcinoma.
AB  - Sarcomatoid renal cell carcinoma (SRCC) is an aggressive tumor variant thought to
      arise predominantly from differentiation of clear cell carcinoma. A few reports
      of SRCC associated with non-clear cell tumors led to the presumption that SRCC
      may arise from any renal cell carcinoma, although direct evidence of this is
      lacking. We report a case of a 70-year-old male patient, who presented with acute
      left upper quadrant abdominal pain and was diagnosed to have SRCC after
      pathological examination. The patient is on high dose interleukin (IL-2)-based
      immunotherapy and is apparently free of disease six months after surgery.

PMID- 21196627
TI  - Nephritic-nephrotic syndrome as a presentation of BK virus infection.
AB  - BK virus (BKV) is increasingly found as an important cause of allograft
      nephropathy. Nephrotic syndrome is not a usual manifestation of BKV nephropathy.
      Here, we report a 12-year-old boy, a case of end-stage renal disease due to
      nephronophthisis, who got the kidney transplanted from a 16-year-old cadaver, and
      after 18 months of uneventful transplantation on triple immunosuppressive therapy
      (mycophenolate mofetil (MMF), cyclosporin and prednisolone), presented with
      nephrotic feature (edema, heavy proteinuria, hypoalbuminemia and hyperlipidemia).
      Kidney biopsy was in favor of BKV infection and eventually ended in graft
      failure.

PMID- 21196628
TI  - Collagenofibrotic glomerulopathy in association with Hodgkin's lymphoma.
AB  - Deposit glomerulopathies are characterized by fibrillary deposits of various
      sizes, mainly in the mesangial area. Collagenofibrotic glomerulopathy is a rare
      type of such fibrillary glomerulopathies characterized by deposits of 60-80 nm
      fibrils in the sub-endothelial and mesangial areas. It is also associated with
      increased levels of serum pro-collagen type III peptide (PIIINP). Although most
      of the initial reports have emanated from Japan, many other scientists around the
      globe have later reported this disease. Possibility of systemic disease affecting
      metabolism of type III collagen is postulated but so far no such association has
      been identified. We report a 26-year-old male patient who presented with
      insidious onset of febrile illness associated with lymphadenopathy and
      proteinuria. Lymph node biopsy revealed features of Hodgkin's lymphoma while
      percutaneous renal biopsy showed features of collagenofibrotic glomerulopathy.

PMID- 21196629
TI  - Rare case of ureteral endometriosis presenting as hydronephrotic kidney.
AB  - A 29-year-old woman presented with unilateral loin pain because of severely hydro
      nephrotic kidney due to deposits of pelvic endometriosis. Double J-stent was
      placed beyond the obstruction and she was started on hormone therapy. The stent
      was removed after three months when back pressure changes had resolved. This case
      is being presented along with a short relevant discussion, due to rarity of
      ureteral involvement by endometriosis.

PMID- 21196630
TI  - Insulin site wound in a renal allograft recipient.

PMID- 21196631
TI  - B.K. polyoma virus nephropathy in renal allograft recipient.

PMID- 21196632
TI  - DMSA SPECT scan of dual transplanted pediatric kidneys in an adult recipient.

PMID- 21196633
TI  - Breast calcifications in women with end-stage renal disease on maintenance
      hemodialysis.

PMID- 21196634
TI  - Fractures in patients of chronic kidney disease on maintenance hemodialysis.

PMID- 21196635
TI  - Free water clearance: its behavior in chronic renal disease at different ages.

PMID- 21196636
TI  - Remission of arterial hypertension after the treatment of a giant renal cyst.

PMID- 21196637
TI  - Giant adrenal cortical carcinoma.

PMID- 21196638
TI  - The elderly with advanced chronic kidney disease.

PMID- 21196639
TI  - Infective endocarditis in chronic hemodialysis patients: experience from Morocco.
AB  - Since the 1960s, regular hemodialysis (HD) was recognized as a risk factor for
      the development of infective endocarditis (IE), particularly at vascular access
      sites. The present report describes our experience at the Etat Major General
      Agadir, Morocco, of taking care of IE in patients on regular dialysis. A
      retrospective analysis was made of five cases of IE in patients receiving regular
      HD having arteriovenous fistula as vascular access. They were sent from four
      private centers and admitted in our formation between January 2004 and March
      2009. Infective endocarditis was detected after 34.5 months following initiation
      of dialysis. The causative organisms included Staphylococcus and Enterococcus in
      two cases each and negative blood culture in one case. A recent history of
      infection (<3 months) of the vascular access was found in three cases. Peripheric
      embolic phenomena were noted in two cases. A pre-existing heart disease was
      common and contributed to heart failure. Mortality was frequent due to valvular
      perforations and congestive heart failure, making the medical treatment alone
      unsatisfactory. Two patients survived and three of our patients received a
      prosthetic valve replacement, with a median survival after surgery of 10.3
      months/person. The clinical diagnosis of infective endocarditis in regularly
      dialyzed patients remains difficult, with the presence of vascular calcification
      as a common risk factor. The vascular catheter infections are the cardinal
      gateway of pathogenic organisms, which are mainly Staphylococcus. The prognosis
      is bad and the mortality is significant, whereas medical and surgical treatments
      are often established in these patients who have many factors of comorbidity.

PMID- 21196640
TI  - Epidemiology of nocturnal enuresis in basic schoolchildren in Aden Governorate,
      Yemen.
AB  - Nocturnal enuresis is a common problem among children and adolescents. Data
      regarding this problem in schoolchildren in Yemen are scarce. This study was
      aimed to determine the prevalence of nocturnal incontinence in Aden school going
      children, describe its severity and identify the relation between nocturnal
      enuresis with personal and family characteristics. The study was a cross
      sectional survey conducted on the public basic schoolchildren in Aden, Yemen, in
      the period November 2007-April 2009. A random, multistage sample of 890 students
      was taken from four districts in eight schools and divided into two strata: males
      and females. Data were obtained by using pre-recorded questionnaire, which was
      completed by parents. The response rate was 73.7% (656 students); 113 (17.2%)
      cases of nocturnal enuresis were encountered. Nocturnal enuresis decreased by age
      from 31.5% at 6-8 years to 8.7% at 15+ years (P < 0.05). Primary nocturnal
      enuresis affected 76.1%, of which the majority of children were bedwetting every
      night. Positive family history of nocturnal enuresis, deeper sleep, daytime
      enuresis, tea drinking, being non working father or with less education showed
      significant association with the occurrence of enuresis in the students.
      Stressful events in the previous 6 months of the study were twice more frequently
      noted. The study concluded that the prevalence of nocturnal enuresis in Aden
      public school children and its associated factors are almost comparable with that
      reported in epidemiological studies from various countries. Health education will
      encourage the parents to be aware, cope with this problem and seek appropriate
      medical advice.

PMID- 21196641
TI  - A two-year retrospective analysis of renal transplant patients in Sri Lanka.
AB  - This retrospective analytical study aimed at making a database of patients who
      underwent renal transplant from 31 December 2004 to 31 December 2006 under the
      Faculty of Medicine renal transplant program. The objective was to build a
      profile of renal transplant patients with focus on post KT infections and
      complications of renal transplants. An interviewer administered questionnaire was
      used. A total of 72 patients were studied; 18 (25%) had died by February 2007.
      Forty-three patients (58.3%) were interviewed in person, 17 were interviewed over
      the phone and 12 patients could not be contacted. Of those who were interviewed,
      28 (38.9%) were on azathioprine, prednisolone and cyclosporine, while 15 (20.8%)
      were on prednisolone, cyclosporin and mycophenolate mofetil. Four patients had
      symptomatic cytomegalovirus infection and five had tuberculosis post transplant.
      Of all infections, the most commonly reported was urinary tract infection (11
      cases). Thirty-three (45.8 %) had received induction therapy with either
      basiliximab (n = 8) or daclizumab (n = 25). Acute rejection was the most commonly
      encountered complication, with nine cases (12.5%) being reported over the study
      period. Of late complications, most were due to immunosuppression. Overall, the 2
      year survival was 75%. There was no significant difference between the centers of
      transplant.

PMID- 21196642
TI  - Immune response to hepatitis B vaccine in health-care workers.
AB  - This study was performed to study the immune response to hepatitis B virus (HBV)
      vaccine in health-care workers. Through a cross-sectional study, relevant
      information and blood samples from 151 healthcare workers at the Firuzgar
      hospital were studied. The age range of the study individuals was 20-59 years,
      with the mean and standard deviation being 35.11 and 10.06, respectively. There
      were 24 males (15.9%) and 127 females (84.1%). The mean and median of months
      after HBV vaccination was 63.42 and 49.00, respectively. The mean and median of
      anti-HBs titer in those who received HBV vaccination was 164.81 and 200 milli
      international units per milliliter (mIU/mL), respectively. Of the 129 HBV
      vaccinated subjects, 103 (68.2%) had anti-HBs titer >10 and 26 (17.2%) had anti
      HBs titer <10. There was no association between gender and anti-HBs titer, but
      vaccination and adequate completion of its courses were associated with higher
      anti-HBs titer (P < 0.05). Also, the logistic regression method showed that the
      association between duration after vaccination and age with anti-HBs titer was
      not statistically significant. Our study suggests that the HBV vaccine
      immunization program had obtained excellent efficacy. There is need for further
      investigation among subjects who are not vaccinated against HBV but are positive
      for anti-HBs as well as in HBV-vaccinated subjects with low anti-HBs titers,
      about possible low-level viremia and other causes of lower vaccine efficacy,
      particularly in health-care workers.

PMID- 21196643
TI  - Risk factors for chronic renal failure in Ivory Coast: a prospective study of 280
      patients.
AB  - Chronic renal failure (CRF) represents the major cause of mortality in the
      nephrology unit in Ivory Coast because the means for appropriate management are
      lacking. The present study was performed to investigate the risk factors for CRF
      so that strategies for prevention could be elaborated. A case-control study was
      performed prospectively at the Yopougon Teaching Hospital in Abidjan from January
      2006 to December 2006. Factors known to cause CRF were investigated in patients
      and controls. Their prevalence rates were compared with the general population. A
      total of 280 patients and 113 controls were recruited. The mean age of the
      patients was 37.88 +/- 13.33 years and that of the controls was 41.5 +/- 9.72
      years. Both genders were equally represented. The main causes of CRF were chronic
      glomerulonephritis (47.48%), with HIV infection accounting for 15% of them, and
      essential hypertension (HTA) (25%). Essential HTA represented the only factor
      which, if untreated, inevitably leads to CRF. Thus, our study indicates that HTA
      is a major public health concern. All efforts should be implemented to reduce the
      high prevalence of HTA and the deleterious effect of this disorder in Ivory
      Coast.

PMID- 21196644
TI  - Non-invasive prediction of esophageal varices: is it possible?

PMID- 21196645
TI  - Hand-assisted endoscopic surgery: lights and shadows.

PMID- 21196646
TI  - Crohn's disease: a surgeon's perspective.
AB  - Crohn's disease (CD) is known for wide anatomic distribution, different
      presentations, life-threatening complications, and multiple modalities of
      management. Its multiple implications are still unaddressed. Since all the
      patients do not show a good response to medical modalities of treatment, a
      significant percentage of these patients are referred to the surgeon for the
      palliation of complications or for the ultimate curative treatment. Since most
      surgeons come across such patients only rarely, it is sometimes difficult for
      them to choose the appropriate procedure at the time of need. Moreover, the
      various surgical modalities available for the different presentations and
      complications of the disease have not been adequately discussed. The aim of this
      review is to offer insight and a detailed account of the management of CD from a
      surgical perspective. This review offers an overview of the various surgical
      options available, their utility in context, and an approach to various scenarios
      of complicated CD.

PMID- 21196647
TI  - Hand-assisted laparoscopic colorectal surgery: initial experience of a single
      surgeon.
AB  - BACKGROUND/AIM: As totally laparoscopic colorectal surgery is considered
      challenging and technically demanding with a long steep learning curve, we
      adopted hand-assisted laparoscopic colorectal surgery as a bridge to totally
      laparoscopic assisted colorectal surgery. This prospective study aims to
      highlight the initial experience of a single surgeon with this technique.
      MATERIALS AND METHODS: A prospective analysis of the first 25 cases of hand
      assisted laparoscopic colorectal resections which were performed by a single
      surgeon over a 15-month period. There were 15 males and 10 females with a mean
      age of 55.5 (range 20-82) years. RESULTS: The indication in majority of cases was
      cancer (76%). The procedures consisted of 18 (72%) various colectomies and 7
      (28%) anterior resections. The operative time ranged between 110-400 (mean 180)
      min. There was one conversion (4%) and the mean operative blood loss was 80
      (range 60-165) ml. The number of lymph nodes retrieved in the cancer cases was 5
      31 (mean 15) nodes. The mean length of hospital stay was five (range 3-10) days.
      The total number of short-term complications was six (24%) and there was one
      death due to anastomatic leak and multiorgan failure. Long-term complications
      after a maximum follow up of 30 months were two incisional hernias at the hand
      port site, but none of the patients developed adhesive small bowel obstruction or
      late anastomotic stricture. Currently all our colorectal procedures are conducted
      laparoscopically. CONCLUSION: Hand-assisted laparoscopic colorectal procedures
      are easy to learn as a good bridge to master totally laparoscopic colorectal
      surgery.

PMID- 21196648
TI  - Long-term follow up of mesenchymal hamartoma of liver--single center study.
AB  - BACKGROUND/AIM: Mesenchymal hamartoma of liver (MHL) is a rare liver tumor of
      childhood. About 200 cases have been reported till now. Most of the work on MHL
      is limited to case reports and there are not many long term follow-up studies. We
      present our 20 years of experience with this uncommon entity. This study aims to
      highlight clinical features, diagnosis and treatment of MHL. MATERIALS AND
      METHODS: All patients with a diagnosis of MHL in last 20 years were included in
      this retrospective study. The patients were evaluated clinically, radiologically
      and pathologically. RESULTS: The total number of patients with a diagnosis of MHL
      was nine. Mean age of the patients was 19.89 +/- 2.75 months. Right lobe was
      involved in eight patients. The prominent clinical features were distension of
      abdomen and anorexia. Surgical options used were hepatic lobectomy, wedge
      resection and enucleation. Histopathology of the specimens showed cysts of
      variable size with normal hepatocytes, bile ducts and connective tissue stroma.
      Overall mortality was one (11.11%). CONCLUSION: MHL is a benign tumor that can
      present with various clinical features. It should be differentiated carefully
      from other liver masses especially malignant ones. The diagnosis can be made with
      the help of radiology and histopathology. Adequate resection is curative in most
      of the cases and long-term follow up is satisfactory.

PMID- 21196649
TI  - Reduction of radiation doses to patients and staff during endoscopic retrograde
      cholangiopancreatography.
AB  - BACKGROUND/AIM: Endoscopic retrograde cholangiopancreatography (ERCP) is
      associated with a considerable radiation exposure for patients and staff. While
      optimization of the radiation dose is recommended, few studies have been
      published. The purpose of this study has been to measure patient and staff
      radiation dose, to estimate the effective dose and radiation risk using digital
      fluoroscopic images. Entrance skin dose (ESD), organ and effective doses were
      estimated for patients and staff. MATERIALS AND METHODS: Fifty-seven patients
      were studied using digital X-ray machine and thermoluminescent dosimeters (TLD)
      to measure ESD at different body sites. Organ and surface dose to specific
      radiosensitive organs was carried out. The mean, median, minimum, third quartile
      and the maximum values are presented due to the asymmetry in data distribution.
      RESULTS: The mean ESD, exit and thyroid surface dose were estimated to be 75.6
      mGy, 3.22 mGy and 0.80 mGy, respectively. The mean effective dose for both
      gastroenterologist and assistant is 0.01 mSv. The mean patient effective dose was
      4.16 mSv, and the cancer risk per procedure was estimated to be 2 * 10(-5).
      CONCLUSION: ERCP with fluoroscopic technique demonstrate improved dose reduction,
      compared to the conventional radiographic based technique, reducing the surface
      dose by a factor of 2, without compromising the diagnostic findings. The
      radiation absorbed doses to the different organs and effective doses are
      relatively low.

PMID- 21196650
TI  - Non-association of IL-12 +1188 and IFN-gamma +874 polymorphisms with cytokines
      serum level in occult HBV infected patients.
AB  - BACKGROUND/AIM: Occult hepatitis B infection (OBI) is identified as a form of
      hepatitis in which despite the absence of detectable HBsAg, HBV-DNA is observed
      in peripheral blood of patients. The main aim of this study has been to
      investigate the association between polymorphisms in +874 of IFN-gamma and +1188
      of IL-12 with their serum level in patients suffering from OBI. MATERIALS AND
      METHODS: In this experimental study, plasma samples of 3700 blood donors were
      tested for the presence of hepatitis B surface antigen (HBsAg) and anti-HBc by
      ELISA. The HBsAg-/anti-HBc+ samples were selected and screened for HBV-DNA by
      PCR. HBV-DNA positive samples were assigned as OBI cases and ARMS-PCR techniques
      were performed to examine the two known polymorphisms within IL-12 and IFN-gamma.
      In addition, the serum levels of IL-12 and IFN-gamma were also determined by
      ELISA. RESULTS: Results of this study demonstrated that, 352 (9.5%) out of 3700
      blood samples were HBsAg-/anti-HBc+ and HBV-DNA was detected in 57/352 (16.1%) of
      HBsAg-/anti-HBc+ samples. Our results showed that groups showed significant
      difference in CC allele of +1188 region of IL-12 and no difference was observed
      in the other evaluated genes. Our results also showed that the alleles of +1188
      region of IL-12 and alleles of +874 of IFN-gamma were also not associated with
      serum level of cytokines. CONCLUSION: According to the results of this study, it
      may be concluded that the polymorphisms in +1188 region of IL-12 and +874 region
      of IFN-gamma would not affect the expression of both cytokines at serum level in
      OBI patients.

PMID- 21196651
TI  - Doppler assessment of hepatic venous waves for predicting large varices in
      cirrhotic patients.
AB  - BACKGROUND/AIM: Color Doppler examination of changes in hepatic venous waveforms
      is being evaluated as a means of prediction of severity of portal hypertension
      and presence of esophageal varices. Normal hepatic venous waveform shows a
      triphasic pattern. In cirrhosis, this pattern changes to a biphasic or monophasic
      pattern. We aimed to study the sensitivity of loss of normal hepatic venous
      waveforms in predicting large varices in a cross-sectional analysis. MATERIALS
      AND METHODS: All patients, admitted or attending the outpatient department, with
      a diagnosis of cirrhosis were included in the study. All patients were subjected
      to oesophagogastroduodenoscopy and Color Doppler examination, and waveform
      patterns in hepatic vein were recorded. The sensitivity and specificity of
      changes in waveform in detecting large varices were studied. RESULTS: A total of
      51 cases were examined. Triphasic waves were seen in 4 (7.8%) cases, biphasic in
      26 (51%) cases, and monophasic in 21 (41.2%) cases. Small varices were seen in 30
      (58.8%) cases and large varices in 21 (41.2%) cases. The sensitivity of loss of
      the triphasic wave pattern in detecting significant varices (Grade 3 or 4) was
      very high (95.23%) and negative predictive value was also high (75%). Severity of
      liver disease as indicated by Child-Pugh and MELD scores did not correlate with
      changes in hepatic venous waveforms. CONCLUSION: Loss of triphasic hepatic venous
      waveform is highly sensitive in predicting significant varices in patients with
      cirrhosis.

PMID- 21196653
TI  - Outcome of laparoscopic cholecystectomy at a secondary level of care in Saudi
      Arabia.
AB  - BACKGROUND/AIM: The first option for gallbladder surgery is laparoscopic
      cholecystectomy. The aim of this study is to analyze the outcomes for all
      patients who underwent laparoscopic cholecystectomy at a secondary level of care.
      PATIENTS AND METHODS: Between 2005 and 2008, 968 consecutive laparoscopic
      cholecystectomies were performed at King Fahad Hospital. We collected and
      analyzed data including age, gender, body mass index (kg/m2), the American
      Society of Anesthesiologists (ASA) class, mode of admission (elective or
      emergency), indication for LC (chronic or acute cholecystitis [AC]), co-morbid
      disease, previous abdominal surgery, conversion to open cholecystectomy,
      complications, operation time, and length of postoperative hospital stay.
      RESULTS: Nine hundred and sixty-eight patients had laparoscopic cholecystectomy
      at the center. There were 824 females and 144 males; the age range was 15-64
      (mean 32.9 +/- 12.7 years). The operating time was 45 to 180 min (median 85 min);
      the complication rate was 4.03% (39 patients). CONCLUSION: Laparoscopic
      cholecystectomy could be performed safely in the majority of patients with
      cholelithiasis, by an experienced surgical team at a secondary level of care.

PMID- 21196652
TI  - Predictors of non-alcoholic fatty liver disease in obese and overweight Egyptian
      children: single center study.
AB  - BACKGROUND/AIM: Pediatric non-alcoholic fatty liver disease (NAFLD) is a global
      problem which has been increasingly recognized with the dramatic rise in
      pediatric obesity. The aim of the present study was to identify the clinical,
      sonographic, and biochemical predictors for NAFLD in obese children. MATERIALS
      AND METHODS: Seventy-six children (2-15 years) were included after an informed
      consent. All were subjected to full anthropometric assessment (including height,
      weight, body mass index, subscapular skin fold thickness, waist and hip
      circumference and calculation of waist: hip ratio), biochemical assessment of
      liver function tests, lipid profile and insulin resistance and sonographic
      assessment of hepatic echogenicity. Liver biopsy when indicated, was done in 33
      patients. RESULTS: Sixteen patients (21%) had elevated ALT and 6 (7.9%) had
      elevated AST. Significant dyslipidemia (low HDL-c, high total cholesterol, high
      LDL-c and triglycerides) and higher insulin resistance were found in obese
      patients (P<0.01). The main sonographic findings were hepatomegaly in 20 patients
      (26.3%) and echogenic liver in 41 patients (53.9%). Liver biopsy showed simple
      steatosis in eight cases (24.2%) and non-alcoholic steatohepatitis (NASH) in
      seven cases (21.2%). Anthropometric measurements, increased hepatic echogenicty
      by ultrasound, insulin resistance and lipid profile were good predictors of NAFLD
      in obese children if assessed together. However, LDL-c was the only sensitive
      predictor (independent variable) for NAFLD in both uni- and multivariate logistic
      regression analyses. CONCLUSION: Dyslipidemia per se is a strong predictor of
      NAFLD among obese Egyptian children.

PMID- 21196654
TI  - Sonographic measurement of abdominal esophageal length as a diagnostic tool in
      gastroesophageal reflux disease in infants.
AB  - BACKGROUND/AIM: This study was conducted to provide sonographic measurements of
      the abdominal esophagus length in neonates and infants with and without
      gastroesophageal reflux disease (GERD) and to investigate its diagnostic value.
      GERD severity was also evaluated and correlated with esophageal length. It is a
      prospective case-control study. MATERIALS AND METHODS: This prospective case
      control study comprised 235 neonates and infants (120 without reflux and 115 with
      reflux). There were 40 children without reflux in each of three age categories:
      less than 1 month, 1-6 months, and 6-12 months. Of the children with reflux, 40
      were less than 1 month old; 37, 1-6 months; and 38, 6-12 months. The abdominal
      esophagus was measured from its entrance into the diaphragm to the base of
      gastric folds in fed infants. GERD was sonographically diagnosed and confirmed by
      a barium meal. The number of refluxes during a 10-min period were recorded.
      RESULTS: Neonates and infants with reflux had a significantly shorter abdominal
      esophagus than subjects without reflux: the mean difference in neonates, 4.65 mm;
      1-6 months, 4.57 mm; 6-12 months, 3.61 mm. CONCLUSIONS: Children with severe
      reflux had a shorter esophagus compared with those with mild and moderate reflux
      only in the neonate group. Therefore, thinking of GERD and carefully looking for
      its symptoms is necessary to avoid unnecessary utilization of healthcare
      resources in children with severe reflux.

PMID- 21196655
TI  - The nutritional, glutathione and oxidant status of elderly subjects admitted to a
      university hospital.
AB  - BACKGROUND/AIM: Malnutrition in elderly patients is common in hospitals, and many
      of the age associated chronic diseases have a common factor, which is oxidative
      stress. The aim of the study was to evaluate the nutritional status, glutathione,
      and oxidant status of elderly patients. PATIENTS AND METHODS: The mini
      nutritional assessment (MNA) was used to determine the nutritional status of
      elderly patients. Glutathione concentration in the whole blood, plasma albumin,
      and thiobarbituric acid-reactive substances (TBARS) levels was measured
      spectrophotometrically by the enzymatic recycling method. In addition, length of
      hospital stay was estimated. All measurements were taken within 48 h after
      admission. RESULTS: The results showed that more than two-thirds of the elderly
      were classified as at risk of malnutrition and malnourished. About 45% and 53%
      elevation in the TBARS was found in at risk of being malnourished and in the
      malnourished groups, respectively, compared to the well-nourished group, but the
      elevation did not reach the significant level. No significant differences in the
      glutathione concentration and in the length of hospital stay were found among the
      three mini-nutritional assessment categories. CONCLUSIONS: The study indicated
      the necessity of performing the MNA test for elderly upon admission to hospitals,
      and more attention needs to be paid to this vulnerable group of people.

PMID- 21196656
TI  - Non-invasive predictors of esophageal varices.
AB  - BACKGROUND/AIM: Current guidelines recommend screening cirrhotic patients with an
      endoscopy to detect esophageal varices and to institute prophylactic measures in
      patients with large esophageal varices. In this study, we aimed at identifying
      non-endoscopic parameters that could predict the presence and grades of
      esophageal varices. PATIENTS AND METHODS: In a prospective study, 229 newly
      diagnosed patients with liver cirrhosis, without a history of variceal bleeding,
      were included. Demographic, clinical, biochemical and ultrasonographic parameters
      were recorded. Esophageal varices were classified as small and large, at
      endoscopy. Univariate analysis and multivariate logistic regression analysis were
      done to identify independent predictors for the presence and grades of varices.
      RESULTS: Of the 229 patients (141 males; median age 42 years; range 17-73 years)
      with liver cirrhosis, 97 (42.3%) had small and 81 (35.4%) had large varices. On
      multivariate analysis, low platelet count (Odd's Ratio [OR], 4.3; 95% confidence
      interval [CI], 1.2-14.9), Child Pugh class B/C (OR, 3.3; 95% CI, 1.8-6.3), spleen
      diameter (OR, 4.3; 95% CI, 1.6-11.9) and portal vein diameter (OR, 2.4; 95% CI,
      1.1-5.3) were independent predictors for the presence of varices. Likewise, for
      the presence of large esophageal varices, low platelet count (OR, 2.7; 95% CI,
      1.4-5.2), Child Pugh class B/C (OR, 3.8; 95% CI, 2.3-6.5) and spleen diameter
      (OR, 3.1; 95% CI, 1.6-6.0) were the independent risk factors. CONCLUSION: The
      presence and higher grades of varices can be predicted by a low platelet count,
      Child-Pugh class B/C and spleen diameter. These may be considered as non
      endoscopic predictors for the diagnosis and management of large grade varices.

PMID- 21196657
TI  - Synchronous adenocarcinoma and mucosa-associated lymphoid tissue lymphoma of the
      colon.
AB  - Mucosa-associated lymphoid tissue (MALT) tumors are a distinct subtype of non
      Hodgkin's lymphoma. Synchronous appearance of adenocarcinoma and colonic MALT
      lymphoma in the same patient is quite rare. In the present report, we describe a
      68-year-old female who presented with a history of bleeding per rectum. She had
      no history of fever, loss of weight or drenching night sweats. Rectal examination
      revealed no abnormality. Colonoscopy showed a large ulceroproliferative mass
      arising from the hepatic flexure, biopsy of which came out to be adenocarcinoma
      of colon. A right hemicolectomy was performed and microscopic study revealed the
      tumor type to be synchronous adenocarcinoma with lymphoma. The final diagnosis of
      this patient turned out to be a synchronous manifestation of both colonic
      adenocarcinoma and colonic MALT lymphoma. Although the patient remains
      asymptomatic two years after surgery, the case highlights the therapeutic dilemma
      that prevails in the definitive management in such scenarios.

PMID- 21196658
TI  - Spontaneous bowel perforation in a neonate with anorectal malformation.
AB  - Gastrointestinal perforation in neonates with anorectal malformations is
      extremely uncommon. Delayed patient presentation is an important factor that
      demands special attention. We present a neonate with anorectal malformation and
      meconium peritonitis following spontaneous bowel perforation. A day 1 neonate was
      referred with features suggested of peritonitis. After adequate resuscitation and
      drainage under local anesthesia, patient was successfully operated for a sigmoid
      perforation and is now awaiting definitive surgery for the anorectal
      malformation.

PMID- 21196659
TI  - A rare case of primary solid intrarectal dermoid.
AB  - Primary rectal teratomas are rare and only few cases have been reported in the
      literature worldwide. These usually occur in females. These are usually cystic
      but very rarely solid variants may occur. We present a case of a solid intra
      rectal dermoid arising primarily in rectum from postero-lateral wall. Excision
      biopsy was done per rectally. Histology revealed the presence of squamous
      epithelium, fat cells, hair follicles, cartilaginous material and columnar lining
      of glandular structures suggestive of mature teratoma. It is usually benign but
      may become malignant, therefore complete resection is advised.

PMID- 21196660
TI  - Modified method of T-tube placement in cases of ruptured choledochal cyst having
      complete loss of anterior wall.
AB  - Survival rates for infants and children who have choledochal cyst with or without
      spontaneous rupture have improved dramatically in the past decades. Despite
      excellent long-term survival for patients with choledochal cyst who undergo
      elective surgery, many significant complications can occur in the patients being
      operated in emergency for rupture of the cyst. Spontaneous rupture of the cyst is
      one such problem resulting in considerable morbidity and mortality in these
      patients. Majority of surgeons manage these cases with T-tube external drainage.
      The conventional methods of T-tube placement for long period has remained simple
      as described in choledochotomies where there is no deficit of the walls of common
      bile duct (CBD). The present technique has been designed specially for the cases
      of ruptured choledochal cyst, where the wall of the CBD gets necrosed leaving
      behind a long gap between the two ends. In these cases, placement of T-tube with
      conventional method is not possible because there is no wall to suture together,
      and make the CBD water tight again to prevent leakage of bile. We found only two
      patients of spontaneous rupture of choledochal cyst with a long gap between two
      ends of CBD because of necrosed anterior wall. In both of these patients, it was
      not possible to put T-tube with traditional method and one would have to opt for
      primary definitive repair despite poor general condition of patients.

PMID- 21196661
TI  - Severe abdominal pain in a post-menopausal obese female.

PMID- 21196662
TI  - An unusual cause of left-sided severe chest pain.

PMID- 21196663
TI  - Inefficiency of rapid urease test for confirmation of Helicobacter pylori.

PMID- 21196664
TI  - Type-1 gall bladder perforation: rare complication of cholelithiasis.

PMID- 21196665
TI  - Chilaiditi syndrome with carcinoma rectum: rare entity.

PMID- 21196666
TI  - ECMO - the way to go.

PMID- 21196667
TI  - Evidence based medicine: can everything be evident?

PMID- 21196668
TI  - Remifentanil in critically ill cardiac patients.
AB  - Remifentanil has a unique pharmacokinetic profile, with a rapid onset and offset
      of action and a plasmatic metabolism. Its use can be recommended even in patients
      with renal impairment, hepatic dysfunction or poor cardiovascular function. A
      potential protective cardiac preconditioning effect has been suggested. Drug
      related adverse effects seem to be comparable with other opioids. In cardiac
      surgery, many randomized controlled trials demonstrated that the potential
      benefits of the use of remifentanil not only include a profound protection
      against intraoperative stressful stimuli, but also rapid postoperative recovery,
      early weaning from mechanical ventilation, and extubation. Remifentanil shows
      ideal properties of sedative agents being often employed for minimally invasive
      cardiologic techniques, such as transcatheter aortic valve implantation and radio
      frequency treatment of atrial flutter, or diagnostic procedures such as
      transesophageal echocardiography. In intensive care units remifentanil is
      associated with a reduction in the time to tracheal extubation after cessation of
      the continuous infusion; other advantages could be more evident in patients with
      organ dysfunction. Effective and safe analgesia can be provided in case of short
      and painful procedures (i.e. chest drain removal). In conclusion, thanks to its
      peculiar properties, remifentanil will probably play a major role in critically
      ill cardiac patients.

PMID- 21196669
TI  - Ketamine has no effect on oxygenation indices following elective coronary artery
      bypass grafting under cardiopulmonary bypass.
AB  - Cardiopulmonary bypass is known to elicit systemic inflammatory response syndrome
      and organ dysfunction. This can result in pulmonary dysfunction and deterioration
      of oxygenation after cardiac surgery and cardiopulmonary bypass. Previous studies
      have reported varying results on anti-inflammatory strategies and oxygenation
      after cardiopulmonary bypass. Ketamine administered as a single dose at induction
      has been shown to reduce the pro-inflammatory serum markers in patients
      undergoing cardiopulmonary bypass. Therefore we investigated if ketamine can
      result in better oxygenation in these patients. This was a prospective randomized
      blinded study. Eighty consecutive adult patients undergoing elective coronary
      artery bypass grafting under cardiopulmonary bypass were included in the study.
      Patients were divided into two groups. Patients in ketamine group received 1mg/kg
      of ketamine intravenously at induction of anesthesia. Control group patients
      received an equal volume of saline. All patients received standard anesthesia,
      operative and postoperative care.Paired t test and independent sample t test were
      used to compare the inter-group and between group oxygenation indices
      respectively. Oxygenation index and duration of ventilation were analyzed.
      Deterioration of oxygenation index was noted in both the groups after
      cardiopulmonary bypass. However, there was no significant difference in the
      oxygenation index at various time points after cardiopulmonary bypass or the
      duration of ventilation between the two groups. This study shows that the
      administered as a single dose at induction does not result in better oxygenation
      after cardiopulmonary bypass.

PMID- 21196670
TI  - Extra corporeal membrane oxygenation after pediatric cardiac surgery: a 10 year
      experience.
AB  - Indications for extra corporeal membrane oxygenation (ECMO) after pediatric
      cardiac surgery have been increasing despite the absence of encouraging survival
      statistics. Modification of ECMO circuit led to the development of integrated
      ECMO cardiopulmonary bypass (CPB) circuit at the author's institute, for children
      undergoing repair of transposition of great arteries among other congenital heart
      diseases (CHD). In this report, they analyzed the outcome of children with CHD,
      undergoing surgical repair and administered ECMO support in the last 10 years.
      The outcome was analyzed with reference to the timing of intervention, use of
      integrated ECMO-CPB circuit, indication for ECMO support, duration of ECMO run
      and the underlying CHD. The results reveal a significantly improved survival rate
      with the use of integrated ECMO-CPB circuit and early time of intervention rather
      than using ECMO as a last resort in the management. The patients with reactive
      pulmonary artery hypertension respond favorably to ECMO support. In all
      scenarios, early intervention is the key to survival.

PMID- 21196671
TI  - Do we need a pulmonary artery catheter in cardiac anesthesia? - An Indian
      perspective.
AB  - There has been considerable controversy regarding the use of pulmonary artery
      catheter (PAC) in clinical practice. Some studies have indicated poor outcome in
      patients who were monitored with PAC. However, these studies, which have
      condemned the use of PAC, were conducted on patients in intensive care units,
      where the clinical scenarios with regard to patients' status are somewhat
      different as compared to those of a cardiac operating room. This study was
      designed to identify the indications of PAC use in cardiac operating rooms. A
      questionnaire was mailed to anasthesiologists in cardiac centers and the response
      was analyzed.The practicing cardiac anesthesiologists recommended the use of PAC
      for following indications in cardiac surgery: coronary artery bypass grafting
      (CABG) with poor left ventricular (LV) function, LV aneurysmectomy, recent
      myocardial infarction (MI), pulmonary hypertension, diastolic dysfunction, acute
      ventricular septal rupture and insertion of left ventricular assist device
      (LVAD).The analysis of responses from practicing anesthesiologists clearly
      indicates that use of a PAC cannot be recommended as a matter of routine, but a
      definite role is suggested in selected groups of patients undergoing cardiac
      surgery.

PMID- 21196672
TI  - Preoperative ephedrine counters hypotension with propofol anesthesia during valve
      surgery: a dose dependent study.
AB  - The prophylactic use of small doses of ephedrine may counter the hypotension
      response to propofol anesthesia with minimal hemodynamic changes. One hundred
      fifty patients scheduled for valve surgery were randomly assigned into five
      groups (n = 30 for each) to receive saline, 0.07, 0.1, or 0.15 mg/kg of
      ephedrine, or phenylephrine 1.5 MUg/kg before induction of propofol-fentanyl
      anesthesia. After induction, patient receiving ephedrine had higher mean arterial
      pressure, systemic vascular resistance (SVRI), cardiac (CI), stroke volume (SVI),
      and left ventricular stroke work (LVSWI) indices. Patients received 0.15 mg/kg of
      ephedrine showed additional increased heart rate and frequent ischemic episodes
      (P < 0.001). However, those who received phenylephrine showed greater rise in
      SVRI, reduced CI, SVI, and LVSWI and more frequent ischemic episodes. We conclude
      that the prophylactic use of small doses of ephedrine (0.07-0.1 mg/kg) is safe
      and effective in the counteracting propofol-induced hypotension during anesthesia
      for valve surgery.

PMID- 21196673
TI  - Fluid infusion into the pericardium resulting from accidental displacement of a
      subclavian venous cannula.
AB  - A patient for double valve replacement developed an unusual complication
      consequent to extra-vascular displacement of a port of a central venous catheter,
      placed through the right subclavian vein. The patient had an uneventful surgical
      course and the trachea extubated after routine mechanical ventilation. Patient
      developed excessive mediastinal drainage later, which was noticed to be watery in
      nature. The source of the drainage was found to be a port of the central venous
      catheter, draining extra-vascular into the subclavian vascular sheath and
      thereafter through the pericardium into the mediastinal drains.

PMID- 21196674
TI  - Utility of intra-operative capnogram to detect branch pulmonary artery
      obstruction following total correction of tetralogy of Fallot.
AB  - Branch pulmonary artery obstruction is one of the prime reasons for re-operation
      in patients who have undergone repair for tetralogy of Fallot. Branch pulmonary
      artery obstruction may develop over a period of time due to dilation of right
      ventricular outflow tract or it may be caused by residual stenosis after
      inadequate repair. This may lead to differential lung perfusion causing
      morbidity. Intra-operative capnogram monitoring reveals ventilation-perfusion
      relationship. We report two cases where the capnogram helped the diagnosis and
      management of branch pulmonary artery obstruction. We found a redundant patch in
      the first and an extra length of the homograft in second case which led to the
      obstruction. However, but for the changes in the intraoperative capnogram, this
      condition may by far remain undiagnosed considering the fact that it does not
      produce hemodynamic changes but can lead to postoperative morbidity.

PMID- 21196675
TI  - Multiple ruptured aneurysm of left sinus of valsalva: a rare entity.
AB  - Aneurysm of sinus of Valsalva is a rare congenital cardiac defect that can
      present with myriad signs and symptoms ranging from trivial to catastrophic
      events like cardiogenic shock and death. As clinical examination is not entirely
      reliable and the patient can sometimes be so ill as to preclude cardiac
      catheterization, echocardiography has become the definitive investigative tool
      not only to define and diagnose the lesion but also to quantify its severity. The
      following is a case report of multiple aneurysms of the left aortic sinus of
      Valsalva rupturing into the left ventricle. Diagnosis is made on multi plane
      transesophageal echocardiography and color Doppler regarding precise
      identification of structural anomalies and shunt locations for perioperative
      assessment and definitive treatment is surgical repair.

PMID- 21196676
TI  - Use of extracorporeal membrane oxygenator support to salvage an infant with
      anomalous left coronary artery from pulmonary artery.
AB  - Anomalous left coronary artery from pulmonary artery (ALCAPA) is a congenital
      acyanotic heart disease where the left coronary artery (LCA) arises from the
      pulmonary artery. This results in the LCA receiving blood supply from the low
      pressure right ventricle having minimal extractable oxygen. The oxygen delivery
      to the left ventricle (LV) is severely hampered causing severe hypoxic LV
      dysfunction early in life. Early surgery prior to serious, irreversible LV
      dysfunction is the key to survival. Children with ALCAPA usually present in their
      first few weeks of life, with severe LV dysfunction. After surgical correction of
      the defect, the myocardium may not recover early from the presurgery myocardial
      dysfunction. We describe a case where extracorporeal membrane oxygenator was
      utilized as a means of ventricular support during this critical postoperative
      period resulting in a favorable outcome.

PMID- 21196677
TI  - Right atrial spontaneous echo-contrast: transesophageal echocardiographic
      features.

PMID- 21196678
TI  - Computerized tomographic coronary angiography in diagnostics of cardiac
      echinococcus.

PMID- 21196679
TI  - What new will EuroSCORE 2010 offer?

PMID- 21196680
TI  - Angiotensin-converting enzyme inhibitor - An innocuous factor behind cardiac
      arrest following induction of anesthesia.

PMID- 21196681
TI  - Perioperative management of a neonate presenting with midgut volvulus and
      obstructed infracardiac total anomalous pulmonary venous connection.

PMID- 21196682
TI  - A comparison of the effects of desflurane, sevoflurane and propofol on on QT, QTc
      and P dispersion on ECG.

PMID- 21196683
TI  - Inhaled nitroglycerin in the treatment of pulmonary hypertension.

PMID- 21196684
TI  - Positioning pressure transducers: upright or upside down?

PMID- 21196685
TI  - Anesthetic induction in coronary artery disease patients with left ventricular
      dysfunction.

PMID- 21196686
TI  - ECG-guided central venous catheterization - can it truly detect internal jugular
      venous malpositioning of subclavian catheter.

PMID- 21196687
TI  - Nonmotor disturbances in Parkinson's disease.
AB  - Nonmotor disturbances (NMDs) affect most patients with Parkinson's disease (PD)
      and often have a profound impact on their quality of life. NMDs such as
      depression, anxiety, fatigue, REM sleep behavior disorder, constipation, delayed
      gastric emptying, altered olfaction and pain can precede the onset of motor
      symptoms. Other NMDs, including hallucinations, dementia, excessive daytime
      sleepiness, insomnia, orthostatic hypotension and bladder disturbances, typically
      appear later in the course of PD. For most NMDs of PD, nondopaminergic and non
      nigrostriatal mechanisms (e.g. neurodegeneration of other transmitter systems in
      the cortex and brainstem, side effects of medications, genetic and psychosocial
      factors) are considered more relevant than the 'classical' dopaminergic
      nigrostriatal dysfunction. The recognition of NMDs requires a high degree of
      clinical suspicion, the use of specific questionnaires and ancillary tests.
      Pharmacological and nonpharmacological approaches can be effective, but for most
      forms of treatment of NMDs, the scientific evidence is limited.

PMID- 21196688
TI  - Radionuclide hysterosalpingography is not a reliable tool for investigation of
      fallopian tube transport--a controlled randomized study using particles of two
      sizes during three different parts of the menstrual cycle.
AB  - BACKGROUND/AIMS: Earlier studies with radionuclide hysterosalpingography (RN-HSG)
      using either small or large particles have shown different results. Some studies
      have questioned the clinical relevance of RN-HSG. The aim of this study was to
      evaluate the RN-HSG method using two different sizes of radio-labelled particles
      during different parts of the menstrual cycle. METHODS: Ten healthy women, 28-40
      years of age (mean 34.5), with proven fertility, regular menstrual cycle, not
      using oral contraceptives and due to undergo laparoscopic sterilization, were
      randomized to RN-HSG after deposition of a solution with either small Albures or
      large MAASOL, (99m)Tc-radio-labelled particles into the cervix uteri.
      Investigations were, for every patient, performed during the follicular, peri
      ovulatory and mid-luteal parts of the menstrual cycle. Transport of radioactivity
      from cervix to uterus and Fallopian tubes was evaluated. RESULTS: The RN-HSG
      investigations could not show any difference between the two different sizes of
      radio-labelled particles. Transport of radioactivity to the Fallopian tube was
      seen only in some cases and most frequently during the peri-ovulatory period.
      CONCLUSION: We found the RN-HSG investigations inconclusive. The RN-HSG method
      does not seem to be a reliable tool for the investigation of Fallopian tube
      transport.

PMID- 21196689
TI  - Are minimally invasive procedures harder to acquire than conventional surgical
      procedures?
AB  - BACKGROUND: It is frequently suggested that minimally invasive surgery (MIS) is
      harder to acquire than conventional surgery. To test this hypothesis, residents'
      learning curves of both surgical skills are compared. METHODS: Residents had to
      be assessed using a general global rating scale of the OSATS (Objective
      Structured Assessment of Technical Skills) for every procedure they performed as
      primary surgeon during a 3-month clinical rotation in gynecological surgery.
      RESULTS: Nine postgraduate-year-4 residents collected a total of 319 OSATS during
      the 2 years and 3 months investigation period. These assessments concerned 129
      MIS (laparoscopic and hysteroscopic) and 190 conventional (open abdominal and
      vaginal) procedures. Learning curves (in this study defined as OSATS score
      plotted against procedure-specific caseload) for MIS and conventional surgery
      were compared using a linear mixed model. The MIS curve revealed to be steeper
      than the conventional curve (1.77 vs. 0.75 OSATS points per assessed procedure;
      95% CI 1.19-2.35 vs. 0.15-1.35, p < 0.01). CONCLUSIONS: Basic MIS procedures do
      not seem harder to acquire during residency than conventional surgical
      procedures. This may have resulted from the incorporation of structured MIS
      training programs in residency. Hopefully, this will lead to a more successful
      implementation of the advanced MIS procedures.

PMID- 21196690
TI  - Are referral centers for non-muscle-invasive bladder cancer compliant to EAU
      guidelines? A report from the vesical antiblastic therapy Italian study.
AB  - INTRODUCTION: Adherence to international guidelines is viewed as a prerequisite
      for optimal medical care delivery. Previously reported surveys for non-muscle
      invasive bladder cancer (NMIBC) employed mailed questionnaires to urologists or
      patients resulting in conflicting degrees of agreement with existing guidelines.
      In the current study, contemporary information on the management of NMIBC was
      generated from a sample of italian centers. PATIENTS AND METHODS: Eight Italian
      referral centers for the treatment of NMIBC were asked to collect information
      relative to all consecutive patients with a histology-proven NMIBC undergoing a
      transurethral resection from January 1 to March 31, 2009. The primary study
      objective was to verify the level of adherence of disease management with
      European guidelines. RESULTS: 344 patients resulted in being evaluable. 49.2% of
      high-risk patients underwent a repeat transurethral resection. Bacillus Calmette
      Guerin was employed in 35% of cases, while chemotherapy was in 22%. An early
      single regimen was adopted in 136 patients and only in 1 out of 3 low-risk
      patients. High-risk NMIBC received bacillus Calmette-Guerin and chemotherapy as
      first-line therapy in 66 and 12.5% respectively. After 3 months, cystoscopy had
      been reported for 82.5% of patients with a recurrence rate of 13%. CONCLUSION:
      Adherence of Italian Institutions to EAU guidelines was optimal when reporting
      baseline variables. Significant degrees of discrepancy emerged in treatment
      choices.

PMID- 21196692
TI  - Accuracy of a portable multisensor body monitor for predicting resting energy
      expenditure in older people: a comparison with indirect calorimetry.
AB  - BACKGROUND: Accurate and comfortable methods are needed to determine resting
      energy expenditure (REE) in older people who are characterized by a lowered
      metabolic rate. The portable SenseWear(r) armband (SWA) body monitor, worn on the
      right upper arm, can easily be used by this age group in an ambulatory manner.
      OBJECTIVE: The purpose of this study was to evaluate the reliability and accuracy
      of the SWA armband in determining REE in healthy, normal-weight older people.
      METHODS: Participants were 49 older, community-dwelling volunteers aged 60-87
      years. Reliability was tested in all subjects. Accuracy was analyzed in 32
      subjects by comparing REE estimated by SWA against REE measured by indirect
      calorimetry as a criterion method. Data were simultaneously and continuously
      recorded for 20 min in the morning. In the same subjects, REE determined by SWA
      from night recording was evaluated for accuracy against indirect calorimetry. The
      agreement between methods was assessed by the Bland-Altman procedure. RESULTS:
      (1) REE measured by SWA was reliable when comparing 2 consecutive measurements
      (typical error: 1.9%). (2) REE calculated from morning recording (1,543 +/- 181
      kcal/24 h) was higher than REE from night recording (1,564 +/- 192 kcal/24 h; p =
      0.018). (3) Compared with REE by indirect calorimetry (1,377 +/- 228 kcal/24 h)
      for accuracy, the SWA overestimated mean REE in the older people by 12 and 14%,
      respectively, for morning and night recording (each p < 0.001). CONCLUSIONS: The
      SWA provides a reliable estimate of REE in healthy older subjects and has the
      advantage of easy handling. The 20-min recording time, which was recommended by
      the manufacturer, can be applied. However, the SWA overestimates REE in this
      group, possibly due to age-related changes in skin conductance and
      thermoregulation, both being measured by sensors of the SWA armband. This
      requires improving the SWA by developing better fitting algorithms for predicting
      REE in older people.

PMID- 21196691
TI  - Hypomaturation amelogenesis imperfecta due to WDR72 mutations: a novel mutation
      and ultrastructural analyses of deciduous teeth.
AB  - BACKGROUND: Mutations in WDR72 have been identified in autosomal recessive
      hypomaturation amelogenesis imperfecta (AI). OBJECTIVE: to describe a novel WDR72
      mutation and report the ultrastructural enamel phenotype associated with a
      different WDR72 mutation. METHODS: A family segregating autosomal recessive
      hypomaturation AI was recruited, genomic DNA obtained and WDR72 sequenced. Four
      deciduous teeth from one individual with a previously published WDR72 mutation,
      extracted as part of clinical care, were subjected to scanning electron
      microscopy, energy-dispersive X-ray analysis and transverse microradiography.
      RESULTS: A novel homozygous nonsense mutation, R897X, was identified in WDR72 in
      a family originating from Pakistan. Ultrastructural analysis of enamel from the
      deciduous teeth of an AI patient with the WDR72 mutation S783X revealed energy
      dispersive X-ray analysis spectra with normal carbon and nitrogen peaks,
      excluding retention of enamel matrix protein. However, transverse
      microradiography values were significantly lower for affected teeth when compared
      to normal teeth, consistent with reduced mineralisation. On scanning electron
      microscopy the enamel rod form observed was normal, yet with inter-rod enamel
      more prominent than in controls. This appearance was unaltered following
      incubation with either alpha-chymotrypsin or lipase. CONCLUSIONS: The novel WDR72
      mutation described brings the total reported WDR72 mutations to four. Analyses of
      deciduous tooth enamel in an individual with a homozygous WDR72 mutation
      identified changes consistent with a late failure of enamel maturation without
      retention of matrix proteins. The mechanisms by which intracellular WDR72
      influences enamel maturation remain unknown.

PMID- 21196693
TI  - Evidence-based and evidence-inspired: an intergenerational approach in the
      promotion of balance and strength for fall prevention.
AB  - The risk of sustaining a fall and fall-related injuries is particularly high in
      children and seniors, which is why there is a need to develop fall-preventive
      intervention programs. An intergenerational approach in balance and strength
      promotion appears to have great potential because it is specifically tailored to
      the physical, social and behavioural needs of children and seniors. Burtscher and
      Kopp [Gerontology, DOI: 10.1159/000322930] raised the question whether our
      previously published mini-review is evidence-based or evidence-inspired. These
      authors postulate that we did not follow a 4-stage conceptual model for the
      development of injury and/or fall-preventive intervention programs. In response
      to this criticism, we present information from the mini-review that comply with
      the 4-stage model incorporating evidence-based and evidence-inspired components.
      We additionally provide information on how to implement an intergenerational
      balance and resistance training approach in a school setting based on a study
      that is being currently conducted.

PMID- 21196694
TI  - Brain homology: Dohrn of a new era?

PMID- 21196695
TI  - Macroorchidism and panhypopituitarism: two different forms of presentation of FSH
      secreting pituitary adenomas in adolescence.
AB  - BACKGROUND: FSH-secreting pituitary adenomas are extremely rare in children and
      are seldom associated with clinical manifestations of high serum gonadotrophin
      levels. Thus, most patients have a late presentation, usually as macroadenomas.
      CASE REPORTS: Two different clinical forms of presentation of FSH-secreting
      pituitary adenomas are reported: one in a 12-year-old boy with macroorchidism due
      to a pituitary microadenoma, probably FSH-secreting, and the other in a 15-year
      old boy with panhypopituitarism due to an FSH-producing macroadenoma. Both
      patients presented slightly high or high FSH with low LH and high inhibin B
      levels. In the first case, the microadenoma was treated medically with
      cabergoline, which failed to reduce FSH and inhibin B levels. No radiological
      progression has been observed despite increasing testicular volume. In the second
      case, surgery was performed on the macroadenoma, leading to a decrease in FSH and
      inhibin B levels. The patient developed severe hypothalamic obesity and is
      currently under treatment with somatostatin. CONCLUSIONS: FSH-secreting pituitary
      tumors have an extremely variable clinical expression. The discrepancy between
      normal or slightly increased FSH and low LH values, together with high inhibin B
      levels, strongly suggests FSH hypersecretion which should be studied.

PMID- 21196696
TI  - The effect of toremifene on lipid metabolism compared with that of tamoxifen in
      vitro.
AB  - BACKGROUND: Tamoxifen (TAM) and toremifene (TOR) prevent estrogen from
      stimulating breast cancer growth and also have agonistic effects in a number of
      physiological systems. TAM is known to increase intracellular triglyceride, but
      the action of TOR on lipid metabolism in vitro has not yet been determined. AIM:
      To compare the effect of TOR on lipid metabolism with that of TAM in vitro, using
      HepG2 cell lines. METHODS: Intracellular concentrations of total cholesterol and
      triglyceride in HepG2 cells were measured by an enzymatic method after TAM or TOR
      treatment. RESULTS: Intracellular concentrations of total cholesterol were
      decreased by both TAM and TOR, but not significantly different from the control
      level. TOR produced no changes in the intracellular concentrations of
      triglyceride, whereas TAM increased the intracellular concentrations of
      triglyceride at concentrations ranging from 10(-7) to 10(-5) mol/l of TAM (p <
      0.05). Moreover, significant differences were noted between the two treated
      groups at concentrations ranging from 10(-9) to 10(-5) mol/l (p < 0.05).
      CONCLUSION: TOR treatment did not increase intracellular concentrations of
      triglyceride, although TAM treatment did so.

PMID- 21196697
TI  - A new possible function for placental pericytes.
AB  - The pericyte is a multifunctional cell closely associated with endothelial cells
      and may play a role in angiogenesis and vessel stabilisation. Re-examination of
      over 1,100 micrographs from archival material used to investigate ultrastructural
      changes in placental development and pathology has identified previously
      undescribed structures associated with the pericyte of the human placental
      terminal villus. These structures take the form of outgrowths from the main body
      of the cell, with a narrow neck rich in cytoplasmic filaments, terminating in
      swollen tips which appear to bleb off the pericyte and form electron lucent
      stromal vesicles. Semi-quantitative analysis indicated that these features are
      present in some placentae from normal, term pregnancies but are increasingly
      found where capillaries show abnormalities such as a failure to form sinusoids,
      as in pregnancies complicated by diabetes, postmaturity, rhesus incompatibility
      and pre-eclampsia. This blebbing is compared with similar phenomena associated
      with apoptosis and zeiosis and it is suggested that it may contribute to fluid
      homeostasis where normal mechanisms are impaired by thickening or damage to
      endothelial cells.

PMID- 21196698
TI  - Cordycepin (3'-deoxyadenosine), an inhibitor of mRNA polyadenylation, suppresses
      proliferation and activates apoptosis in human epithelial endometriotic cells in
      vitro.
AB  - BACKGROUND/AIMS: Endometriosis is a benign but chronic disorder associated with
      pelvic pain and infertility. Enhanced proliferation and reduced apoptosis
      susceptibility are characteristics of endometriosis. Cordycepin is a poly(A)
      polymerase inhibitor. It induces shortening of poly(A) tails, leading to
      destabilization of mRNAs and finally to proliferation inhibition and cell death
      in normal and tumor cells. The potential of cordycepin to block proliferation and
      survival of 11z human immortalized epithelial endometriotic cells was determined.
      METHODS: 11z cell cultures were treated with cordycepin. Cordycepin-induced
      inhibition of proliferation and alterations in protein expression and protein
      phosphorylation were determined by the methyl thiazolyl tetrazolium assay and
      immunoblot analysis, respectively. RESULTS: Cordycepin induced the rapid and
      significant upregulation of the cell cycle progression inhibitor p21 and the
      downregulation of the cell cycle progression promoter cyclin D(1), finally
      leading to the inhibition of the proliferation of 11z human epithelial
      endometriotic cells. Cordycepin reduced the phosphorylation of the p38 mitogen
      activated protein kinase and the retinoblastoma protein. It also activated
      caspase-dependent, intrinsic apoptosis, as documented by the proteolytic cleavage
      of the caspase-9, caspase-3 and the poly(ADP ribose) polymerase 1 precursor.
      CONCLUSION: The mRNA polyadenylation inhibitor cordycepin inhibits proliferation
      and survival of endometriotic cells.

PMID- 21196699
TI  - Inadvertently found thoracic ectopic liver confirmed without surgery.

PMID- 21196700
TI  - Ectopic intrathyroidal thymus in children: a long-term follow-up study.
AB  - BACKGROUND: Ectopic intrathyroidal thymus has recently been reported in children
      as a cause of surgery and/or invasive diagnostic procedures when mistaken for a
      thyroid nodule. Thymus has a unique appearance at ultrasound (US). METHODS: We
      report a follow-up study (mean 34 months, range 6-84) performed by US on 9
      children (5 females) with a mean age of 6.3 +/- 3.2 years with intrathyroidal
      thymic inclusions diagnosed by US as 'incidentalomas'. None has palpable nodules.
      RESULTS: Intrathyroidal thymic inclusions appeared on US as a hypoechoic area,
      with regular linear or punctuate internal hyperechoic echoes. The 2 oldest
      patients (13 and 17 years) showed a regression in both size and hypoechogenicity
      of thymic inclusions over time--reflecting the normal thymic involution with
      advancing age. CONCLUSIONS: Indeed, the lack of progression seen in our 9
      patients over a mean time of 34 months confirmed the substantially benign and
      self-limited nature of this process. The increasing use of thyroid
      ultrasonography in children may result in an increased detection of
      intrathyroidal thymic inclusions--an embryologic anomaly that should be
      considered in the differential diagnosis of thyroid nodules in children and
      adolescents.

PMID- 21196702
TI  - Prenatal detection of congenital heart defects: a survey on clinical practice in
      Spain.
AB  - INTRODUCTION: Second-trimester fetal screening for congenital heart defects (CHD)
      included in routine obstetric care provides relevant information for decision
      making. The aim of this study was to describe the clinical practice of prenatal
      detection of CHD in terms of the process and results. METHODS: The
      characteristics and results of ultrasound screening for major CHD were documented
      using data provided by hospitals for a national survey in Spain over the period
      of 2004-2006. Sixty-seven percent of eligible centers (56/83), covering 36% of
      total births nationwide, responded to the survey; 33 of these returned complete
      data regarding the screening results. RESULTS: The number of major CHD occurring
      in the centers which provided data with results of screening was 1,060. The
      overall prenatal detection rate of major CHD was 65.7% (95% CI 57.8-74.7), but
      the detection rate in the routine second-trimester scan was 52.6% (95% CI 45.6
      60.8). In 61% of these cases the parents chose to terminate the pregnancy. Two
      independent predictors of increased detection by center were identified: first,
      the uniformity and systematic character of the examination of the heart showing
      at least the 4-chamber view and outflow tracts (prevalence ratio 1.3, 95% CI 1.0
      1.8) and second, the local availability of specialists in fetal echocardiography
      (prevalence ratio 1.4, 95% CI 1.1-1.9). CONCLUSIONS: The detection of major CHD
      in the first half of pregnancy has an important impact on parental decision
      making. The prenatal screening program for CHD should be globally strengthened in
      terms of qualifications and methodological approaches. To improve its performance
      locally, close collaboration with fetal heart specialists should be promoted.

PMID- 21196701
TI  - Sentinel lymph node biopsy status is a key parameter to stratify the prognostic
      heterogeneity of malignant melanoma in high-risk tumors >4.0 mm.
AB  - BACKGROUND: The value of sentinel lymph node biopsy (SLNB) as a useful strategy
      to assess the risk of future metastasis in high-risk melanomas (>4.0 mm) is
      controversially discussed. OBJECTIVES: In a single-center retrospective study,
      the prognostic relevance of SLNB and other risk factors in the subgroup of
      melanomas >4.0 mm was investigated and compared to previously published results.
      METHODS: Using Kaplan-Meier estimates and Cox regressions, we assessed the
      prognostic relevance of SLNB in our subcohort of 87 patients with thick melanomas
      >4.0 mm (T4). The mean follow-up for this subgroup was 51 months. We compared SLN
      value as compared to ulceration. RESULTS: SLN and ulceration, analyzed as
      separate risk factors as well as their combination, predicted a highly reduced
      life expectancy in terms of recurrence-free survival (RFS) in our cohort of
      patients. SLN, but not ulceration, also predicted overall survival (OS).
      CONCLUSIONS: Positive SLNB is an essential predictor of RFS and OS in T4 melanoma
      patients, whereas ulceration lacked significance with respect to OS in our
      cohort. Our data thus suggest the routine use of SLNB also for T4 melanoma and
      may therefore allow to optimize risk-stratified therapeutic regimens.

PMID- 21196703
TI  - Vitamin D, UV, and skin cancer in the elderly: to expose or not to expose?
AB  - There is mounting concern about vitamin D insufficiency, especially in the ageing
      population. Increases in indoor lifestyle, obesity, car travel, clothing habits,
      the use of photo-protective makeup, and campaigns driven by dermatologists,
      governments, and the cosmetic industry to avoid or protect against the sun as
      much as possible are contributing to this trend. In a recent article in
      Gerontology, Barysch et al. [1] recommend that the ageing population avoid any
      'intentional' UV radiation as well as 'minimize sun exposure' based on known
      dangers of developing skin cancer. They warn that 'studies with vitamin D
      supplements reported increased risks of prostate and esophagus cancer as well as
      atopy in childhood' and concluded that 'adequate levels of vitamin D are
      essential for the elderly', but do not suggest which level is optimal. I will
      argue that the ageing population should keep their serum 25-(OH)-vitamin D(3) (25
      (OH)-D) levels in the 75-100 nmol/l range. An oral cholecalciferol intake of
      ~2,000 IU/day is recommended as a supplement throughout the year for those who
      cannot enjoy the sun in summer or only during 'vitamin D winter' for the others.

PMID- 21196704
TI  - Homozygosity for the c.917A->T (p.N306l) polymorphism in the EVER2/TMC8 gene of
      two sisters with epidermodysplasia verruciformis Lewandowsky-Lutz originally
      described by Wilhelm Lutz.
AB  - BACKGROUND: Epidermodysplasia verruciformis Lewandowsky-Lutz (EV) is a rare
      genodermatosis, characterised by development of numerous verrucous skin lesions
      caused by specific genotypes of human papillomaviruses belonging to the beta
      papillomavirus genus. The EV loci were mapped to chromosome 2p21-p24 (EV2) and
      17q25 (EV1). On chromosome 17, 2 adjacent related genes--EVER1/TMC6 and
      EVER2/TMC8--were identified. We reinvestigated 2 patients originally described by
      Wilhelm Lutz in 1946 with the aim to document the natural course of the disease
      and confirm his diagnosis. METHODS: PCR fragments specific for exons with short
      flanking intron sequences of EVER1/TMC6 and EVER2/TMC8 genes from patients' DNA
      were amplified using sequence information. The single-nucleotide polymorphism
      (SNP) rs7208422 was studied, using restriction fragment length polymorphism
      analysis. RESULTS: In the index patient, we identified a homozygous TT genotype
      in exon 8 of the EVER2/TMC8 gene (c.917A->T, p.N306I). The same mutation could
      thereafter be detected in her sister from paraffin-embedded skin. CONCLUSION: We
      have followed one of the first patients described with EV in Basel, Switzerland,
      in 1930 until today and demonstrated the TT genotype (SNP rs7208422) in the
      EVER2/TMC8 gene in this index patient and her sister. The results underline the
      possible relevance of SNP rs7208422 by influencing the susceptibility to beta
      papillomaviruses and their oncogenic potential.

PMID- 21196705
TI  - Relationship between the three-dimensional structure of the human plantar
      epidermis and the dermoscopic patterns seen in melanocytic nevi.
AB  - OBJECTIVE: Our aim was to investigate the relationship between the distribution
      of the dermoscopic patterns seen in plantar melanocytic nevi and the 3
      dimensional structures of the epidermis. METHODS: The precise locations of 69
      melanocytic nevi on the sole and the border areas were investigated, with
      attention paid to each dermoscopic pattern. In addition, the basal surfaces of
      the plantar epidermis from 14 anatomical areas were observed by scanning electron
      microscopy (SEM). RESULTS: In the weight-bearing area, melanocytic nevi with a
      fibrillar pattern were preferentially observed. Those with a lattice-like pattern
      were observed in the arch area, whereas those with a crista reticulated pattern
      were seen in the border area. On SEM observations, transverse ridges formed a
      couple of parallel lamellae on the crista profunda limitans (limiting ridges).
      Between the limiting ridges and the crista profunda intermedia (intermediate
      ridges), the transverse ridges had different shapes according to the anatomical
      location of the sole. CONCLUSION: These results suggest that the characteristic
      dermoscopic patterns seen in plantar melanocytic nevi simulate the arrangement of
      transverse ridges.

PMID- 21196706
TI  - Pregabalin antagonizes copper-induced toxicity in the brain: in vitro and in vivo
      studies.
AB  - BACKGROUND: Copper plays key roles in brain metabolism. Disorders of copper
      metabolism impact on neural signaling. The intracellular and extracellular
      concentrations of copper are tightly regulated. Pregabalin is a drug with
      multiple modes of action and has a high-affinity binding site for the alpha2delta
      subunit of voltage-gated calcium channels. METHODS: Assessment of neuroprotective
      effects of pregabalin using cell culture, transcription studies, microdialysis
      and neurophysiological assessment in rats. RESULTS: In vitro, copper decreased
      markedly the survival of neuronal cells and enhanced the production of nitric
      oxide (NO). Transcription of NO synthase (NOS) 1-3 and PGC-1a (a key regulator of
      mitochondrial biogenesis) was activated. In vivo, copper impaired the NMDA
      mediated regulation of glutamate in the brain, increased the production of NO and
      enhanced markedly the excitability of the motor cortex. Pregabalin had
      antagonistic effects both in vitro and in vivo. CONCLUSION: Our experiments
      highlight that pregabalin antagonizes the neurotoxic effects of copper. We argue
      that pregabalin exerts neuroprotective effects by silencing the overexcitability
      state induced by copper. We propose a possible use of pregabalin for treatment of
      disruption of copper homeostasis.

PMID- 21196708
TI  - COL7A1 Recessive mutations in two siblings with distinct subtypes of dystrophic
      epidermolysis bullosa: pruriginosa versus nails only.
AB  - Dystrophic epidermolysis bullosa (DEB) is a rare, clinically heterogeneous,
      blistering genodermatosis inherited as either autosomal dominant or recessive
      trait. All DEB forms are caused by mutations in the COL7A1 gene, which encodes
      for type VII collagen, the major component of the anchoring fibrils ensuring
      epithelial-mesenchymal adhesion. Major determinants of clinical heterogeneity in
      DEB are COL7A1 mutation types and their consequences at mRNA and protein levels;
      nevertheless, siblings with the same genetic alterations can manifest highly
      variable clinical signs. Here, we report novel compound heterozygous recessive
      COL7A1 missense mutations in 2 siblings presenting different DEB clinical
      subtypes. Our findings document the rare occurrence of recessive inheritance for
      the nails only DEB variant and emphasize the role of acquired phenotype-modifying
      factors in DEB pruriginosa pathogenesis.

PMID- 21196707
TI  - Growth pattern of untreated boys with simple virilizing congenital adrenal
      hyperplasia indicates relative androgen insensitivity during the first six months
      of life.
AB  - CONTEXT: Mild forms of simple virilizing congenital adrenal hyperplasia (CAH) may
      be missed in newborn screening. In the pre-newborn-screening era, missed
      diagnosis of simple virilizing CAH was not infrequent in boys. Elevated adrenal
      androgens lead to accelerated growth and bone maturation. Traditional treatment
      of CAH consists of the suppression of ACTH through glucocorticoid replacement, in
      an attempt to reduce excessive androgen production. OBJECTIVE: To retrospectively
      analyze early growth pattern and bone maturation in untreated boys with simple
      virilizing CAH. PATIENTS: In the pre-newborn screening era, 13 boys had a late
      diagnosis of simple virilizing classical CAH. Diagnosis of 21-hydroxylase
      deficiency was confirmed by mutation analysis of the CYP21A2 gene in all
      patients. Growth data were retrospectively collected from standarized preventive
      medical checkups at the regular pediatrician until the time of diagnosis of CAH.
      RESULTS: Length was 0.1 +/- 0.8 SDS (mean +/- SD) at birth, 0.2 +/- 1 SDS at 3
      months, 0.2 +/- 0.9 SDS at 6 months, 0.7 +/- 1 SDS at 1 year, +1.1 +/- 0.9 SDS at
      2 years and +1.8 +/- 1.2 SDS at 4 years. At diagnosis, mean chronological age was
      4.4 +/- 1.6 years and height SDS was 2 +/- 1.7. Bone age was accelerated (9.4 +/-
      4 years) at diagnosis. Signs that had led to diagnosis were pubic hair (n = 11),
      accelerated growth rate (n = 6) and birth of an affected sister (n = 3). Despite
      late start of hydrocortisone treatment, mean final height was -1 +/- 0.9 SDS.
      Seven of 18 patients had a final height within 1 SD of target height. CONCLUSION:
      Height velocity is not markedly increased in untreated boys with simple
      virilizing CAH in the first 6 months of life, indicating that infants are
      relatively androgen insensitive during that period. After the first 6 months of
      life, growth velocity increases significantly and elevated androgens lead to
      advanced skeletal maturation. This observation has implications for lower
      hydrocortisone doses to be used in CAH children during the first 6 months of
      life. In addition, staying alert for clinical symptoms and signs of simple
      virilizing CAH is still warranted, since mild forms may be missed in newborn
      screening.

PMID- 21196709
TI  - Diagnostic pitfall: pigmented lesion of the nipple--correlation between
      dermoscopy, reflectance confocal microscopy and histopathology.
AB  - We present an unusual case of a nevus of the nipple changing during pregnancy
      which caused a diagnostic pitfall. Nevi on the nipple and areola are infrequent,
      and diagnostic criteria for clinical, dermoscopy or reflectance confocal
      microscopy examination for nevi in this 'special location' are still missing. We
      comment on the literature on dermoscopic findings in mammary lesions and their
      management during pregnancy, as well as the challenging histopathology of nevi
      along the milk line. Finally, we focus on two main limitations of reflectance
      confocal microscopy: the misinterpretation of dendritic cells and the limitation
      of the imaging depth.

PMID- 21196710
TI  - Factors associated with premature skin aging (photoaging) before the age of 55: a
      population-based study.
AB  - BACKGROUND: Precise factors associated with premature skin aging, or photoaging,
      in the general population are unknown. OBJECTIVE: To examine the risk factors for
      photoaging in a Queensland community. METHODS: A cross-sectional study of 1,400
      randomly selected residents aged 20-54 years, using casts of the back of the hand
      (surface microtopography) and dermatological assessment of photoaging. RESULTS:
      83% of the participants had premature skin aging, worsening after the age of 30.
      Severe neck wrinkling was 3 times more likely in men and some 4 times more likely
      in fair-skinned people (odds ratio, OR=3.86, 95% confidence interval, CI=2.40
      6.23). Red hair and mainly outdoor work or leisure raised the odds of
      microtopographic photoaging. Current smoking was strongly associated with facial
      comedones and telangiectasia, and among current smokers, the microtopography
      grade was significantly associated with moderate and heavy smoking measured by
      pack-years of exposure, with OR=3.18 (95% CI=1.38-7.35) in the heaviest (>20 pack
      years) smoking category compared with 1-7 pack-years. CONCLUSIONS: Premature skin
      aging is common in the subtropics, more severe in men and the fair-skinned. It is
      associated with high sun exposure during leisure or work, and moderate to heavy
      smoking, and therefore is preventable.

PMID- 21196711
TI  - Computer evolution of chemotaxis in model nematodes.

PMID- 21196712
TI  - Equine disorders of sexual development in 17 mares including XX, SRY-negative,
      XY, SRY-negative and XY, SRY-positive genotypes.
AB  - We described the clinical, cytogenetic and molecular findings of 17 clinical
      equine cases presented for abnormal sexual development and infertility. Six
      horses with an enlarged clitoris had an XX, SRY-negative genotype, which
      displayed male-like behavior (adult individuals). Bilateral ovotestes were noted
      in 2 of those cases, while another case showed increased levels of circulating
      testosterone. Six horses with a female phenotype, including normal external
      genitalia, had an XY, SRY-negative genotype. These individuals had small gonads
      and an underdeveloped internal reproductive tract. Four horses with normal
      appearing external genitalia had an XY, SRY-positive genotype, 3 of them had
      hypoplastic testes and male-like behavior. In addition, one young filly with
      enlarged clitoris and hypoplastic testes had the same genotype but did not show
      male-like behavior due to her age. Three of these horses were related with 2
      being siblings. These findings demonstrate the diversity of disorders of sexual
      development seen in the horse. Furthermore, they emphasize the need for further
      research to identify genes involved in abnormal sex determination and
      differentiation in the horse.

PMID- 21196713
TI  - Cytogenetic mapping of the retroelements Rex1, Rex3 and Rex6 among cichlid fish:
      new insights on the chromosomal distribution of transposable elements.
AB  - To enhance our understanding of the organization of the genome and chromosome
      evolution of cichlid fish species, we have isolated and physically mapped onto
      the chromosomes the transposable elements (TEs) Rex1, Rex3 and Rex6, which are
      conserved in teleost fish, in the chromosomes of African and South American
      cichlid species. The physical mapping of different Rex elements showed that they
      are primarily compartmentalized in the pericentromeric heterochromatic regions,
      although dispersed or clustered signals in euchromatic regions were also
      observed. The presence of TEs in heterochromatin can be correlated with their
      role in the structure and organization of heterochromatic areas (such as
      centromeres) or with the lower selective pressure that act on these gene-poor
      regions. The Rex elements were also concentrated in the largest chromosome pair
      of the Nile tilapia, Oreochromis niloticus. This chromosome pair is supposed to
      have originated by fusions, demonstrating the possible involvement of TEs with
      chromosome rearrangements. Besides general patterns of chromosomal distribution,
      comparative analysis suggests that Rex elements could differ in their chromosomal
      distribution among different fish groups or species and that intrinsic aspects of
      the genomes could influence the spread, accumulation or elimination of TEs.

PMID- 21196714
TI  - Second-hand tobacco smoke and allergens - double jeopardy for childhood asthma
      exacerbations.

PMID- 21196715
TI  - Joy and chagrin of an editor.

PMID- 21196716
TI  - Clinical follow-up of hydroxyurea-treated adults with sickle cell disease.
AB  - Hydroxyurea-derived clinical and biological benefits and safety were
      retrospectively studied for 123 adult patients from 2 sickle cell disease
      referral centers during a total follow-up of 654 patient-years and total
      hydroxyurea exposure of 549 patient-years. Fifty-six adverse events occurred
      (incidence: 12%/patient-year), with leg ulcers being the most frequent. Adverse
      events could arise at any time and were usually reversible. No malignancy was
      observed. Clinical and biological benefits of our cohort were similar to those
      previously reported. Based on this relatively long retrospective study, the
      risk/benefit ratio for moderate hydroxyurea doses was satisfactory.

PMID- 21196717
TI  - Aggressive systemic mastocytosis associated with mesangioproliferative
      glomerulonephritis.
AB  - BACKGROUND/AIMS/METHODS: Aggressive systemic mastocytosis (ASM) is a subtype of
      systemic mastocytosis, which comprises a heterogenous group of disorders
      characterized by infiltration of bone marrow, skin, liver, spleen, lymph nodes
      and gastrointestinal tract by neoplastic mast cells. There is lack of data on the
      association of ASM with renal involvement, as kidney is not among the known
      organs affected by ASM. RESULTS/CONCLUSIONS: To the best of our knowledge, this
      is the first case of ASM associated with mesangioproliferative glomerulonephritis
      and monoclonal gammopathy of undetermined significance, without the presence of
      nephrotic syndrome. The patient's clinical course and the intriguing family
      history, along with the treatment selection are described. Finally, the proposed
      possible pathophysiological mechanisms explaining the renal involvement of our
      patient are discussed.

PMID- 21196718
TI  - ADAMTS-13 antigen and activity levels in thrombocytopenic disorders including
      thrombotic thrombocytopenic purpura in Kuwait.
AB  - BACKGROUND/AIMS: While deficiency of a disintegrin and metalloprotease with
      thrombospondin-1-like domains (ADAMTS-13) was reported as the basis for the
      pathogenesis of thrombotic thrombocytopenic purpura (TTP), low levels have also
      been found in other thrombocytopenic disorders. This study was conducted to
      characterize the activity and antigen levels of ADAMTS-13 and von Willebrand
      factor (vWF) in patients with different thrombocytopenic disorders in Kuwait.
      METHODS: Forty healthy subjects and 41 patients with different thrombocytopenic
      disorders were recruited for this study. ELISA tests were used to measure ADAMTS
      13 and vWF activity and antigen levels in patients and controls. RESULTS: All TTP
      patients had severely deficient ADAMTS-13 activity (<5%), which was significantly
      lower than that of controls (p < 0.001). Severe deficiency of ADAMTS-13 was also
      found in some, but not all, patients with idiopathic thrombocytopenic purpura,
      acute leukemia and sepsis. CONCLUSIONS: This study is the first to report ADAMTS
      13 levels in this part of the world. ADAMTS-13 was found to be severely deficient
      in TTP patients. We present evidence that significantly lower levels of ADAMTS-13
      were not specific for TTP and can be found in other thrombocytopenic disorders.
      We also hypothesize that clinical manifestation of TTP may not be solely due to
      ADAMTS-13 deficiency, and there might be other contributing factors, since the
      deficiency was also found in some healthy controls.

PMID- 21196719
TI  - Clinicopathologic characteristics of CD99-positive diffuse large B-cell lymphoma.
AB  - BACKGROUND: CD99 immunoreactivity has been documented in a variety of tumors,
      including lymphoid malignancies such as anaplastic large-cell lymphomas. However,
      few studies have investigated the prognostic impact of CD99 in diffuse large B
      cell lymphoma (DLBCL). METHODS: Using conventional paraffin embedding,
      immunoperoxidase staining and tissue microarrays, we retrospectively investigated
      CD99 expression in 155 DLBCL patients. RESULTS: Of the 155 DLBCL patients, 60
      (38.7%) were positive for CD99. CD99 positivity was significantly associated with
      advanced stage (p < 0.01), higher risk group according to the International
      Prognostic Index risk score (p < 0.01) and non-germinal center B cell-like type
      (p = 0.01). The difference in progression-free survival (PFS) between CD99+ and
      CD99- groups was statistically significant (p = 0.04), even though the difference
      in overall survival was not (p = 0.74). Multivariate analysis demonstrated that
      CD99 expression was marginally correlated with PFS. CONCLUSION: To the best of
      our knowledge, this is the first report on the clinicopathologic characteristics
      of CD99+ DLBCL, particularly unique clinicopathologic features.

PMID- 21196720
TI  - Second allogeneic stem cell transplantation in a patient with hypoplastic
      myelodysplastic syndrome following a primary diagnosis of aplastic anaemia.

PMID- 21196721
TI  - Podocyte number in the maturing rat kidney.
AB  - BACKGROUND/AIMS: The podocyte is an important cell for maintaining the normal
      structure and function of the glomerulus. In recent years much attention has been
      given to the number of podocytes in glomeruli. During this time there has been a
      debate as to whether podocytes can divide after the capillary-loop stage of
      development. The aim of this study was to use an unbiased counting method to
      determine if podocyte number increases after the capillary-loop stage of
      development. METHODS: The fractionator/disector method was used to count
      podocytes in glomeruli from rats aged 1 day, 5, 12, and 24 weeks. Glomerular
      volume was also measured with the unbiased Cavalieri principle and used to
      calculate the density of podocytes per glomerulus. RESULTS: The number of
      podocytes did not increase from the capillary-loop stage of glomerular
      development to 24 weeks of age. Glomerular volume increased 3.6-fold during this
      time, which resulted in a decrease of podocyte density as the rats aged.
      CONCLUSION: The study documents that the number of podocytes is stable after the
      capillary-loop stage of glomerular development. The data does not confirm but
      adds evidence that podocytes do not divide from the capillary-loop stage of
      glomerular development to 24 weeks of age in the normal rat.

PMID- 21196722
TI  - Serum uric acid is inversely related to acute ischemic stroke morbidity in
      hemodialysis patients.
AB  - AIM: Elevated serum uric acid (sUA) is usually associated with a high occurrence
      of acute ischemic stroke (AIS) in the general population. The aim of this study
      is to evaluate the role of sUA in AIS among hemodialysis (HD) patients. METHODS:
      We followed up the occurrence of AIS in 226 HD patients for 18 months from
      January 2009 to June 2010. The parameters included demographic characteristics,
      duration of HD, sUA, serum albumin, and other parameters. Logistic regression was
      performed to evaluate the function of SUC levels in the occurrence of AIS.
      RESULTS: A total of 43 patients suffered from AIS. By univariate logistic
      regression analysis an inverse association was observed in sUA level with the
      risk of AIS (p = 0.005), but the significance of this inverse association was
      attenuated while adjusted for age, gender and pulse pressure (PP) (p = 0.029),
      and even weakened while adjusted for age, gender, PP and diabetes nephropathy
      (DN) (p = 0.065), and finally abolished after adjustment for age, gender, PP, DN,
      hsCRP and pre-albumin. CONCLUSION: This study indicates an inverse association
      between sUC and the occurrence of AIS in HD patients. Demographic characteristics
      and malnutrition-microinflammation syndrome seem to play a significant role in
      this association.

PMID- 21196723
TI  - Docosahexaenoic acid is an independent predictor of all-cause mortality in
      hemodialysis patients.
AB  - BACKGROUND: Dietary n-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid
      (DHA) and eicosapentaenoic acid have been shown to reduce cardiovascular
      mortality. Patients on hemodialysis (HD) have a very high mortality from
      cardiovascular disease. Fish consumption reduces all-cause mortality in patients
      on HD. Moreover, n-3 PUFAs, especially DHA levels in red blood cells (RBCs), are
      associated with arteriosclerosis in patients on HD. The aim of this study was to
      determine whether DHA levels in RBCs predict the mortality of patients on HD in a
      prospective cohort study. METHODS: A cohort of 176 patients (64.1 +/- 12.0 (mean
      +/- SD) years of age, 96 men and 80 women) under HD treatment was studied. The
      fatty acid composition of their RBCs was analyzed by gas chromatography. RESULTS:
      During the study period of 5 years, 54 deaths occurred. After adjustment for 10
      confounding factors, the Cox hazard ratio of all-cause mortality of the patients
      on HD in the highest DHA tertile (>8.1%, 15 deaths) was 0.43 (95% CI 0.21-0.88)
      compared with those patients in the lowest DHA tertile (<7.2%, 21 deaths).
      CONCLUSION: The findings suggest that the level of DHA in RBCs could be an
      independent predictor of all-cause mortality in patients on HD.

PMID- 21196724
TI  - Nongenomic effects of aldosterone on renal protein expressions of pEGFR and
      pERK1/2 in rat kidney.
AB  - BACKGROUND: In vitro studies have demonstrated that aldosterone elicits
      nongenomic actions by enhancing protein expressions of phosphorylated epidermal
      growth factor receptor (pEGFR) and phosphorylated extracellular signal-regulated
      kinases 1/2 (pERK1/2). There are no available in vivo investigations regarding
      this action of aldosterone on renal pEGFR-pERK1/2 protein expressions. METHODS:
      Male Wistar rats received normal saline solution, low-dose (LA: 150 MUg/kg BW) or
      high-dose aldosterone (HA: 500 MUg/kg BW) by intraperitoneal injection. After 30
      min, protein abundances and localizations of renal pEGFR and pERK1/2 were
      determined by Western blot and immunohistochemistry. RESULTS: Plasma aldosterone
      levels were increased in LA and HA groups (p < 0.001). Aldosterone enhanced renal
      pEGFR and pERK1/2 protein abundances (p < 0.001). HA showed a greater stimulation
      on pEGFR immunoreactivity than LA in the glomerulus, vasa recta, and thin limb of
      Henle's loop in the inner medulla area. LA provided more reactivity of pERK1/2 in
      the thick ascending limb of Henle's loop, outer medullary collecting duct, and
      proximal straight tubule, whereas HA illustrated more pERK1/2 activation in the
      glomerulus, peritubular capillary, and inner medulla region. CONCLUSION: This is
      the first in vivo study which demonstrates that aldosterone, via the nongenomic
      pathway, could elevate pEGFR and pERK1/2 protein abundances and expressions in
      the rat kidney. These results indicate that aldosterone induces phosphorylation
      of EGFR upstream of ERK1/2.

PMID- 21196725
TI  - The histopathology of revision cochlear implantation.
AB  - The current study evaluates histopathologic changes in the temporal bones of 4
      human subjects who underwent revision cochlear implantation. Specimens were
      removed at autopsy, fixed and prepared for histological study by standard
      techniques. Specimens were serially sectioned, reconstructed by two-dimensional
      methods, and the tracks of the initial and revision cochlear-implant electrodes
      identified. The tracks were of three types: a 'common track' (shared by the
      reimplantation electrode and initial electrode), 'two tracks' (where the
      reimplantation electrode was in a different track than that of the initial
      electrode) and 'one track' (where the reimplantation electrode extended beyond
      the initial electrode, forming a single track). Associated histopathologic
      findings (new bone formation, fibrosis or inflammatory cells, and cochlear fluid)
      were evaluated for the three types of tracks. In all 4 subjects, the insertion
      depth of the revision cochlear implant was deeper than that of the initial
      cochlear implant. The primary track of the initial implantation did not interfere
      with insertion of a revision cochlear implant, and the trajectory of the revision
      electrode did not always follow the primary track. In cochlear segments with a
      common track or two tracks, the mean (across-subject) percent area of the
      extraelectrode cochlear duct filled with abnormal (new bone or fibrotic) tissue
      (43.2%) was significantly greater than the mean percent area occupied by fluid
      (13.4%; t = 3.12, d.f. = 19.9, p = 0.003).

PMID- 21196726
TI  - Infection-mediated vasoactive peptides modulate cochlear uptake of fluorescent
      gentamicin.
AB  - Inflammatory mediators released during bacterial infection include vasoactive
      peptides such as histamine and serotonin, and their serum levels are frequently
      elevated. These peptides also modulate the vascular permeability of endothelial
      cells lining the blood-brain and blood-labyrinth barriers (BLB). These peptides
      may also modulate the permeability of the BLB to ototoxic aminoglycoside
      antibiotics prescribed to resolve bacterial sepsis. To test this hypothesis, we
      compared the effect of histamine and serotonin on the cochlear distribution of
      fluorescently conjugated gentamicin (GTTR) in control animals at 0.5, 1 and 3 h
      after injection of GTTR. The intensity of GTTR fluorescence was attenuated at 1 h
      in the histamine group compared to control mice, and more intense 3 h after
      injection (p < 0.05). In the serotonin group, the intensity of GTTR fluorescence
      was attenuated at 0.5 and 1 h (p < 0.05) and was increased at 3 h compared to
      control animals, where GTTR intensities peaked at 1 h and then plateaued or was
      slightly decreased at 3 h. This biphasic pattern of modulation was statistically
      significant in the apical turn of the cochlea. No difference in the intensity of
      GTTR fluorescence was observed in kidney proximal tubules. Systemic increases in
      serum levels of vasoactive peptides can modulate cochlear uptake of gentamicin,
      likely via permeability changes in the BLB. Conditions that influence serum
      levels of vasoactive peptides may potentiate aminoglycoside ototoxicity.

PMID- 21196727
TI  - Long-term language levels and reading skills in mandarin-speaking prelingually
      deaf children with cochlear implants.
AB  - The aim of this study was to document receptive and expressive language levels
      and reading skills achieved by Mandarin-speaking children who had received
      cochlear implants (CIs) and used them for 4.75-7.42 years. The effects of
      possible associated factors were also analyzed. Standardized Mandarin language
      and reading tests were administered to 39 prelingually deaf children with Nucleus
      24 devices. The Mandarin Chinese version of the Peabody Picture Vocabulary Test
      was used to assess their receptive vocabulary knowledge and the Revised Primary
      School Language Assessment Test for their receptive and expressive language
      skills. The Graded Chinese Character Recognition Test was used to test their
      written word recognition ability and the Reading Comprehension Test for their
      reading comprehension ability. Raw scores from both language and reading
      measurements were compared to normative data of nor- mal-hearing children to
      obtain standard scores. The results showed that the mean standard score for
      receptive vocabulary measurement and the mean T scores for the receptive
      language, expressive language and total language measurement were all in the low
      average range in comparison to the normative sample. In contrast, the mean T
      scores for word and text reading comprehension were almost the same as for their
      age-matched hearing counterparts. Among all children with CIs, 75.7% scored
      within or above the normal range of their age-matched hearing peers on receptive
      vocabulary measurement. For total language, Chinese word recognition and reading
      scores, 71.8, 77 and 82% of children with CIs were age appropriate, respectively.
      A strong correlation was found between language and reading skills. Age at
      implantation and sentence perception scores account for 37% of variance for total
      language outcome. Sentence perception scores and preimplantation residual hearing
      were revealed to be associated with the outcome of reading comprehension. We
      concluded that by using standard tests, the language development and reading
      skill of Mandarin-speaking children who use CIs from a young age appear to fall
      within the normal range of their hearing age mates, at least after 4.8-7.4 years
      of experience. However, to fully evaluate the fine linguistic skills of these
      subjects, a more detailed study and longer follow-up period are needed.

PMID- 21196728
TI  - Hospital admissions for ischemic stroke: does long-term exposure to air pollution
      interact with major risk factors?
AB  - BACKGROUND: The aim was to investigate whether the effects of major risk factors
      for ischemic stroke were modified by long-term exposure to air pollution in
      Scania, southern Sweden. METHODS: Cases were defined as first-ever ischemic
      strokes in patients born between 1923 and 1965 during 2001-2006 (n = 7,244). Data
      were collected from The Swedish National Stroke Register (Riks-stroke) and the
      Malmo and Lund Stroke Registers. Population controls were matched on age and sex.
      Modeled outdoor annual mean NO(x) concentrations were used as proxy for long-term
      exposure to air pollution. Heterogeneity across NO(x) categories was tested for
      smoking, hypertension, diabetes mellitus, atrial fibrillation and physical
      inactivity. Data were analyzed as case-control data and to some extent as case
      only data, with logistic regression analysis. RESULTS: The case-control odds
      ratios for ischemic stroke in association with diabetes were 1.3 [95% confidence
      interval (CI): 1.1-1.6] and 2.0 (95% CI: 1.2-3.4) in the lowest and highest NO(x)
      category, respectively (p value for testing heterogeneity across the categories =
      0.056). The case-only approach gave further support for the risk associated with
      diabetes to increase with NO(x) (p for trend = 0.033). We observed no main effect
      of mean NO(x) or any conclusive effect modifications between NO(x) and smoking,
      hypertension, atrial fibrillation or physical inactivity. CONCLUSIONS: In a low
      level air pollution area, the risk for ischemic stroke associated with diabetes
      seemed to increase with long-term exposure to air pollution.

PMID- 21196729
TI  - Basilar artery diameter is a potential screening tool for Fabry disease in young
      stroke patients.
AB  - BACKGROUND: Fabry disease (FD) is a rare hereditary lysosomal storage disease
      that has been highlighted as a possible etiology of stroke at a young age.
      Enlarged basilar artery diameters (BADs) have been demonstrated in FD, and we
      hypothesize that they might be useful for the screening of FD in young stroke
      patients. The aim of this study was to compare BADs of young stroke patients
      without FD to those of FD patients and of healthy age-matched controls. METHODS:
      BADs were measured using MR angiography in 3 age- and gender-matched groups: 25
      FD patients (aged 36.5 +/- 11.0 years), 26 non-FD stroke patients and 20 healthy
      controls. RESULTS: Compared to the non-FD stroke patients, FD patients had
      significantly enlarged BADs. FD patients could be significantly separated from
      stroke patients by BADs (area under the curve = 0.89, 95% confidence interval
      0.81-0.98). Eighty-six percent of all subjects could be correctly classified by
      BADs (sensitivity 84%, specificity 88.5%). CONCLUSIONS: Enlarged BADs were able
      to detect FD within a cohort of FD, stroke patients and healthy controls. BAD
      measurement could be an easily obtainable and sensitive screening tool for FD in
      young stroke patients.

PMID- 21196730
TI  - Acute kidney infarction secondary to intracardiac thrombus embolization in a
      patient with ischemic dilated cardiomyopathy.
AB  - Acute renal infarction due to emboli represents a very rare but significant
      threat for kidney loss, and the clinical presentation is challenging. The
      differential diagnosis of massive renal thrombi includes all other causes of
      abdominal pain, and they can be easily misdiagnosed as renal colic due to
      nephrolithiasis. Although there are a few case reports regarding the possibility
      that cardiac emboli may cause acute kidney infarction, intracardiac thrombi
      within the ventricular cavity diagnosed by echocardiography as a cause of such
      renal artery occlusion have never been reported in patients with cardiomyopathy.
      Herein, we describe a 39-year-old male with a history of ischemic dilated
      cardiomyopathy. He was admitted to our hospital with left upper abdominal pain
      and vomiting. After serial examinations and tests, the diagnosis of acute renal
      infarction due to intracardiac thrombus embolization as a result of severely
      reduced cardiac function was made.

PMID- 21196731
TI  - Left ventricular diverticulum associated with neovascularization in an adult.
AB  - We present a case of congenital left ventricular diverticulum, associated with
      neovascularization involving the distal segments of all the coronary arteries.
      There were no other thoraco-abdominal or cardiac anomalies. To our knowledge,
      this is the first reported case of ventricular diverticulum associated with
      neovascularization in an adult.

PMID- 21196732
TI  - Effects of xylitol on survival of mutans streptococci in mixed-six-species in
      vitro biofilms modelling supragingival plaque.
AB  - Xylitol has been claimed to reduce mutans streptococci (MS) in dental plaque by
      energy-consuming futile metabolic cycles. This study aimed to investigate the
      effects of xylitol on MS in an in vitro 6-species oral biofilm model. Each
      multispecies biofilm contained either a laboratory reference strain, a fresh
      isolate, a xylitol-sensitive or a xylitol-resistant strain of Streptococcus
      mutans or Streptococcus sobrinus. Biofilms, grown on pellicle-coated
      hydroxyapatite discs, were fed with a glucose/sucrose-supplemented medium 3 times
      daily for 45 min and incubated in saliva between feedings. Before or after
      feeding, biofilms were exposed to either 7.5% xylitol, 7.5% sorbitol or to saliva
      (control) for 20 min. After 64.5 h, biofilms were harvested and the microbial
      composition was analysed by non-selective and selective culturing. Strain
      variability in the ability to colonize biofilms was observed. However, the
      response patterns in the biofilms to the 4 polyol treatments were similar. None
      of the MS were inhibited by xylitol provided either before or after feeding.
      Sorbitol given before feeding did not affect microbial growth whereas sorbitol
      provided after feeding showed a slight, albeit statistically significant increase
      in MS counts for some of the tested strains. It did so at the expense of
      Streptococcus oralis, which decreased in numbers. The present findings do not
      support the contention that xylitol reduces MS in plaque by futile metabolic
      cycles.

PMID- 21196733
TI  - A new method for intraluminal gastrointestinal stromal tumor resection using
      laparoscopic seromuscular dissection technique.
AB  - INTRODUCTION: It is difficult to confirm the location of an intraluminal
      gastrointestinal stromal tumor (GIST) and to laparoscopically determine the
      appropriate resection line. We report a new technique for the resection of GISTs
      using the laparoscopic seromuscular dissection (LSD) technique, which can be
      preformed regardless of the tumor location. METHODS: Since 2009, 5 patients have
      undergone LSD technique for the resection of an intraluminal GIST. The tumor
      location was confirmed endoscopically, and the exact resection line was marked
      laparoscopically. After 10% glycerin was injected into the submucosal layer, LSD
      was performed circumferentially. The tumor was exteriorized into the abdominal
      cavity and dissected using a linear stapling device. RESULTS: The average
      operation time for this procedure was 134.4 +/- 18.6 min, and the mean estimated
      blood loss was 10 +/- 8.9 ml. None of the 5 cases required open surgery. There
      was no tumor rupture or disruption or any other perioperative complications using
      this technique. CONCLUSION: We conclude that the LSD technique may be a safe and
      minimally invasive method for the resection of intraluminal GISTs, regardless of
      the tumor location.

PMID- 21196734
TI  - Long-term outcomes after laparoscopic Nissen fundoplication for reflux
      laryngitis.
AB  - BACKGROUND: The surgical treatment of gastroesophageal reflux-induced reflux
      laryngitis remains controversial. The aim of this study was to determine both
      long-term objective endoscopic findings and subjective symptomatic outcomes after
      laparoscopic Nissen fundoplication in patients operated on for reflux laryngitis.
      METHODS: 40 consecutive patients with pH-proven reflux laryngitis underwent
      laparoscopic Nissen fundoplication between 1998 and 2002. 68% (n = 27) of these
      patients underwent an endoscopic evaluation and 90% (n = 36) were available for
      the subjective long-term outcome (personal interviews). RESULTS: At a median
      follow-up of 91 months there were no disrupted plications, none of the patients
      had esophagitis but 3 recurrent hiatal hernias were detected. 61% of the patients
      reported no or only mild reflux laryngitis symptoms postoperatively and 69% of
      the patients evaluated their voice quality improved after surgery. 94% of the
      patients were satisfied with their surgical result. With benefit of hindsight,
      11% of the patients would not choose surgical treatment and 42% had reinitiated
      antireflux medications postoperatively. CONCLUSION: The majority of pH-proven
      gastroesophageal reflux-induced reflux laryngitis patients attain long-term
      symptomatic benefit and satisfaction on the surgical outcome, and with proper
      patient selection laparoscopic Nissen fundoplication provides a feasible long
      term treatment option for reflux laryngitis.

PMID- 21196735
TI  - Value of laparoscopic splenectomy as salvage treatment for relapsed
      thrombocytopenia after partial splenic arterial embolization.
AB  - BACKGROUND/AIMS: Recently, partial splenic arterial embolization (PSE) has become
      a supportive intervention for cirrhotic patients with hypersplenism in the
      administration of interferon therapy. However, relapsed thrombocytopenia is often
      observed in patients following PSE. This study aimed to report the clinical
      efficiency of laparoscopic splenectomy as a salvage treatment for relapsed
      thrombocytopenia following PSE. METHODS: From 2005 to 2009, 6 patients with prior
      PSE treatment underwent laparoscopic splenectomy. We reviewed the surgical method
      of laparoscopic splenectomy and the peri- and postoperative outcomes. RESULTS:
      Laparoscopic splenectomy effectively provided sufficient increases in patient
      platelet counts. In all patients, laparoscopic splenectomy was performed safely
      with no significant complications despite PSE-associated dense adhesion to the
      diaphragm and/or retroperitoneal attachments. CONCLUSION: Laparoscopic
      splenectomy provides a sufficient increase in patient platelet counts in relapsed
      thrombocytopenia following PSE. Therefore, laparoscopic splenectomy appears to be
      a superior supportive therapy for the treatment of thrombocytopenia in cirrhotic
      patients.

PMID- 21196736
TI  - Circular stapler-assisted extraperitoneal colostomy.
AB  - AIMS: To report and evaluate the clinical value of circular stapler-assisted
      extraperitoneal colostomy. METHODS: We performed circular stapler-assisted
      extraperitoneal colostomy following Miles' operation in 22 patients over a 2-year
      period from March 2007 to March 2009. The efficiency and safety of the operation
      were evaluated. RESULTS: The length of surgery was 15 +/- 5 min, and all the
      colostomies were successfully completed during the first procedure. No
      complications such as anastomotic infections, hemorrhage, necrosis, or
      invagination occurred after surgery. No scar contraction, stoma stenoses,
      intestinal obstructions, or parastomal hernias were found during the follow-up
      period of 24-72 months. All the colostomies functioned well. CONCLUSION: Circular
      stapler-assisted extraperitoneal colostomy can be a safe and effective procedure
      to improve the outcome of surgery for rectal cancer. This is one of the few
      studies attempting stapled colostomy, and at present the technique appears
      promising but warrants a longer follow-up period and additional study, in
      particular a prospective trial including a control group.

PMID- 21196737
TI  - Predictive factors for percutaneous endoscopic gastrostomy in patients with
      spontaneous intracranial hemorrhage.
AB  - BACKGROUND: Dysphagia is frequent after hemorrhagic stroke, and some of the
      affected patients require prolonged enteral nutrition, most often via
      percutaneous endoscopic gastrostomy (PEG) tubes. The identification of patients
      at risk of prolonged dysphagia permits earlier tube placement and helps guide
      clinicians in the decision-making process. METHODS: This retrospective study
      included all patients with spontaneous ICH admitted to a tertiary university
      hospital from 2007 until 2009 (n = 208). Fifty-one patients received PEG tubes.
      PEG tube placement was conducted in ventilated patients within 30 days and in
      spontaneously breathing patients if swallowing did not improve within 14 days.
      RESULTS: Twenty-five percent of patients received PEG tubes. Those patients had
      larger lobar hemorrhages, intraventricular hemorrhage and occlusive hydrocephalus
      and higher ICH scores. Furthermore, patients with PEG scored worse on Glasgow
      Coma Scale (GCS), National Institute of Health Stroke Scale (NIHSS) and Acute
      Physiology And Chronic Health Evaluation (APACHE II), more frequently needed
      mechanical ventilation, and had more inflammatory and renal complications. A
      multivariate regression analysis identified GCS, occlusive hydrocephalus,
      mechanical ventilation, and systemic sepsis as independent risk factors for PEG
      tube placement. CONCLUSION: Disease severity and neurocritical care complications
      represent the major influencing parameters for PEG tube placement in spontaneous
      ICH patients.

PMID- 21196738
TI  - Mobile intimal flap in the brachiocephalic artery diagnosed by ultrasonography.

PMID- 21196739
TI  - Tolerability and acceptance of prolonged low/delayed mitoxantrone regimens in
      patients with worsening multiple sclerosis.
AB  - BACKGROUND: Severe side effects such as cardiotoxicity and leukemia limit long
      term use of mitoxantrone (MTX) despite its recommendation in patients with
      malignant forms of relapsing remitting (RR) and secondary progressive (SP)
      multiple sclerosis (MS). METHODS: We analyzed data on tolerability, measured as
      compliance with the treatment, and patients' acceptance of an alternative MTX
      treatment schedule in 12 patients with aggressive RRMS or SPMS treated for at
      least 3 years with low/delayed dose MTX. RESULTS: Twelve patients received 9-17
      cycles of MTX treatment, with individual median doses of 7.6-12.16 mg/m(2)/course
      during 36 to 114 (median 49.5) months resulting in cumulative doses of 101.9
      143.0 mg/m(2) per patient. The overall follow-up period was 37-122 (median 69.5)
      months. Treatment was well tolerated and appreciated by patients according to the
      Treatment Satisfaction-Visual Analogue Scale. No significant safety findings were
      seen concerning cardiological, hematological and oncological follow-up. The
      patients showed a stabilization of disease progression and a reduced annual
      relapse rate. CONCLUSIONS: Delayed, and/or dose-reduced, long-term MTX regimens
      over several years might represent a feasible alternative treatment for MS
      patients without any other therapeutic options.

PMID- 21196740
TI  - Comet-tail-like inflammatory infiltrate to polymer filaments develops in tension
      free conditions.
AB  - BACKGROUND: Mesh reinforcement in hiatal hernia repair becomes more frequent but
      is charged by complications such as erosion or stenosis of the oesophagus. These
      complications are accompanied by an intense inflammatory infiltrate around the
      polymer fibres. To characterize this effect, the response to polypropylene fibres
      in the absence of tension was examined. METHODS: In rats, polypropylene sutures
      (USP size 1, 3-0 and 7-0) were placed in the subcutis of the abdominal wall
      without knot or tension. On postoperative days 3, 7 and 21, specimens were
      excised. The expressions of c-myc, beta-catenin, Notch3, COX-2, CD68 and Ki-67
      were measured by immunohistochemistry. RESULTS: In the absence of tension,
      sutures were surrounded by a foreign body granuloma with an inflammatory
      infiltrate not encircling the fibre but forming almost symmetric comet-tail-like
      infiltrates on opposite sides. The expression of c-myc, beta-catenin, Notch3, COX
      2, CD68 and Ki-67 was significantly reduced over time in the comet tail, but not
      in the granuloma. CONCLUSIONS: Even in tension-free conditions, surgical sutures
      cause a foreign body response with infiltrates of inflammatory cells. This
      reaction is shaped like a comet tail, and its extension depends on the diameter
      of the used fibre. Therefore, for reduction of perifilamental infiltrates, not
      only absence of tension is required, but also a small-sized fibre textile.

PMID- 21196741
TI  - Fournier's gangrene: series of twenty patients.
AB  - BACKGROUND AND PURPOSE: Fournier's gangrene (FG) is a rare, rapidly progressive,
      fulminant form of necrotizing fasciitis of the genital, perianal and perineal
      regions. Our aim is to investigate the clinical signs, symptoms and factors which
      affect the clinical results of patients with FG in our clinic. PATIENTS AND
      METHODS: 20 patients having FG were admitted to our department during the past 6
      year period. Age, gender, diabetes mellitus (DM), duration of symptoms, FG
      severity index score (FGSIS), colostomy, hospitalization time and number of
      debridements were investigated for their effects. RESULTS: 13 of our patients
      were male, 7 of them were female. The mean age was 52.2 years (range: 30-80
      years). 85% of our patients had DM as a predisposing factor. The mean
      hospitalization time was 19.7 days (range: 6-45 days), and overall mortality was
      20% (4 patients). Age and FGSIS have been found to be statistically significant
      factors among the parameters studied. DISCUSSION: FG is still an important
      disease with high mortality rates in spite of the developments in intensive care
      units and new-generation antibiotics. In conclusion, we have found that the age
      and FGSIS of the patient are the most important effecting factors.

PMID- 21196742
TI  - [Multimorbidity, comorbidity and phytotherapeutic multicomponent mixtures as
      drugs].

PMID- 21196743
TI  - Reducing systematic review to a cut and paste.

PMID- 21196744
TI  - Changes of Intestinal Microflora in Patients with Rheumatoid Arthritis during
      Fasting or a Mediterranean Diet.
AB  - BACKGROUND: therapeutic dietary interventions are effective treatments for
      rheumatoid arthritis (RA). The mechanisms to affect inflammation and clinical
      outcome in rheumatoid arthritis are only partly understood. Alterations in
      intestinal microflora are believed to be associated with disease activity in RA.
      AIM: to evaluate changes in short-chain fatty acid (SCFA) profiles and clinical
      outcome in RA during medical fasting or mediterranean diet. METHODS: Fifty
      consecutive in-patients from an Integrative Medicine Department were included in
      a prospective observational, non-randomised, clinical trial. Patients underwent a
      7-day fasting (MF) therapy or a Mediterranean diet (MD) as part of a multimodal
      therapeutic treatment approach. RESULTS: the mean Disease Activity Score (DAS-28)
      significantly decreased in both groups (p < 0.001) from 5.7 +/- 0.9 to 4.1 +/-
      1.3 in the MF and from 5.4 +/- 1.4 to 4.5 +/- 1.3 in the MG group, with no
      significant difference between the groups (p = 0.115). VAS showed a consecutive
      decrease of pain in both study groups which was significantly higher in the
      fasting group on day 7 (p = 0.049). No significant differences between the study
      groups were found in the profile of total-fatty acids (p = 0.069), butyrate (p =
      0.611) and propionate (p = 0.419). Measurement of acetate, however, showed
      significant differences (p = 0.044) with an increase from 17,4 +/- 9.8 MUmol/g to
      21,4 +/- 16.4 MUmol/g in MF compared to a decrease from 15,2 +/- 10.4 MUmol/g to
      13,8 +/- 9.3 MUmol/g in MD. There was no significant correlation between dietary
      induced changes of SCFA and changes of disease activity. CONCLUSION: alterations
      in SCFA were found in terms of significant changes to increased acetate levels in
      the fasting group. A correlation between changes of SCFA from intestinal
      microflora and disease activity in RA could not be revealed. Further studies are
      needed in the field of dietary inducible changes of the intestinal microflora in
      patients with RA.

PMID- 21196745
TI  - Long-term effects of traditional Chinese medicine and hypnotherapy in patients
      with severe endometriosis--a retrospective evaluation.
AB  - BACKGROUND: 15% of patients with severe endometriosis suffer from pain symptoms
      in spite of pharmacological and surgical treatments. In this retrospective study
      we aimed to assess the effectiveness of a combined therapy of Traditional Chinese
      medicine and hypnotherapy (systemic autoregulation therapy, SART) as a novel
      treatment for endometriosis-associated symptoms. PATIENTS AND METHODS: 47
      patients with severe endometriosis, which were treated with SART, were followed
      up by standardized telephone interviews. Follow-up data were compared to baseline
      assessments. RESULTS: median follow-up time was 5 years. The median intensity of
      endometriosis-associated pain had decreased from 8 to 3 points on a 0-10 point
      visual analogue scale (p < 0.001). 18 patients (38%) were free of pain, and the
      number of patients using pain medication had decreased from 38 to 19 (from 81% to
      40%). 17 out of the 31 women trying for a pregnancy (55%) showed a total of 21
      births at follow-up. Exploratory analyses revealed that larger decreases in pain
      scores correlated significantly with longer treatment durations, suggesting a
      dose-response relationship. CONCLUSION: treatment of endometriosis with a
      holistic approach of Chinese medicine and hypnotherapy may result in a
      substantial reduction of pain as well as increased birth rates in patients with
      therapy-refractory endometriosis. Randomized controlled studies to further
      investigate the effectiveness of SART are highly warranted.

PMID- 21196746
TI  - [Evaluation of methods of traditional chinese medicine at the clinic at
      Steigerwald Part 2: therapy success and sustainability].
AB  - INTRODUCTION: in 2008, we described the documentation system of the 'Klinik am
      Steigerwald'. Now, we report on the results gained with this system, especially
      on the therapeutic success and its sustainability. PATIENTS AND METHODS: we
      evaluated 1,972 in-patients treated between 1999 and 2007. 74% of these patients
      were followed for up to 24 months. The therapeutic success achieved at the time
      of discharge from hospital was comparable in patients with follow-up and in
      patients lost to follow-up. Therefore, no relevant bias has to be assumed.
      RESULTS: at discharge from hospital complaints had improved markedly or somewhat
      in 62-77% of the patients. 2 years after discharge from hospital between 62 and
      85% of the patients said that their complaints had improved as compared to the
      time before admission. This is also true for progressive diseases and if
      medication had been reduced. The proportion of days with inability to work
      decreased from 21.6% before admission to 16.0% at 0-6 months after discharge to
      14.0% at 6-12 months after discharge to 11.9% at 18-24 months after discharge
      from hospital. Special focus is laid on Morbus Crohn /colitis ulcerosa and
      polyneuropathy which are core areas of the 'Klinik am Steigerwald'. CONCLUSION:
      documentation of the therapeutic success and its sustainability is essential for
      an evidence based medicine. Assessment of therapeutic success by complaints of
      patients is according to the idea of quality of life. This holds for modern as
      well as for traditional medical procedures like e.g., traditional Chinese
      medicine.

PMID- 21196747
TI  - Acupuncture for improving chronic rhinosinusitis complicated with persistent
      allergic rhinitis. A prospective observational study.

PMID- 21196748
TI  - [Limits and benefits of non-controlled therapy-related observations].
AB  - In the age of evidence-based medicine, results from prospective controlled
      interventional studies are awarded the highest priority for determining the
      efficacy of a therapeutic measure. In contract, the role of non-controlled
      therapy-related observations is very low. This conception is due to the fact that
      in the absence of a control group it is impossible to assess a causal
      relationship between an administered therapy and the subsequent clinical
      outcome.Nevertheless, non-controlled therapeutic observations may be clinically
      relevant. Four domains may be distinguished : besides their importance for
      learning and teaching, such observations can contribute to evaluate which
      benefits results gained in controlled studies have in daily practice. On the
      other hand, they may point to hitherto unknown phenomena, such as the detection
      of new indications or unexpected therapeutic side effects. Finally, they may act
      as an important source for the generation of hypotheses about therapeutic
      measures, thus fostering further research.

PMID- 21196750
TI  - [Looking back].

PMID- 21196751
TI  - Social structure and group dynamics of the Cao Vit gibbon (Nomascus nasutus) in
      Bangliang, Jingxi, China.
AB  - The Cao Vit gibbon (Nomascus nasutus) was rediscovered in 2002 in Vietnam and
      then in 2006 in China. This is the only known population with about 110
      individuals located along the China-Vietnam border. Little is known about it
      other than its population size and distribution. We describe the social structure
      and group dynamics of the Cao Vit gibbons in China based on 2 years of monitoring
      from 2007 to 2009. Four established study groups at this site consisted of 1
      adult male, 2 adult females and 2-6 offspring. Two juveniles in 2 groups
      disappeared during the research. Four infants were born in 3 groups from November
      2008 to February 2009. In 2 of the groups, both adult females had dependent
      infants. These observations suggest that Cao Vit gibbons live in polygynous
      groups, contrary to the usual monogamous group with only 1 adult female, but
      nevertheless similar to the social organization of both N. concolor and N.
      hainanus. We observed a coordinated dispersal of 1 adult male and 2 large
      juveniles, and the male formed a pair with a newly arrived female. Our
      observations support a growing awareness of variability in gibbon social
      organization.

PMID- 21196752
TI  - A direct comparison of scan and focal sampling methods for measuring wild
      chimpanzee feeding behaviour.
AB  - Focal sampling is the most accurate method for measuring primate activity budgets
      but is sometimes impractical. An alternative is scan sampling, in which the
      behaviour of the group is recorded at regular intervals. The simplest technique
      is to record whether at least 1 animal is engaged in the behaviour of interest.
      By direct comparison with focal data collected simultaneously on the same
      population, we assess the validity of this simple group level sampling method for
      studying chimpanzee (Pan troglodytes schweinfurthii) feeding behaviour. In a 13
      month study at Kanyawara, Kibale National Park, Uganda, group level scan sampling
      provided statistically similar measures of broad diet composition to those
      produced by focal data, despite considerable seasonal variation. Monthly means of
      the percentage of time spent consuming non-fig fruit calculated from group level
      scan sampling were highly correlated with those from focal sampling. This
      validates previous methodology used to identify periods of high energy
      availability. However, group level scans tended to overestimate the percentage of
      observation time spent feeding, particularly for adult males. We conclude that
      this method of group level scan sampling provides valuable data for
      characterizing broad diet choice in chimpanzees and other species, but may be of
      limited use for estimating individual feeding time.

PMID- 21196753
TI  - The role of the house dust mite-induced innate immunity in development of
      allergic response.
AB  - House dust mite (HDM) represents one of the most common sources of aeroallergens
      worldwide and more than 50% of allergic patients are sensitized to these
      allergenic molecules. HDM allergy research in the past has been mainly focused on
      adaptive, mite allergen-dependent immune responses. In recent years it has become
      clear that, although the allergen-specific CD4+ Th2 cells orchestrate HDM
      allergic response,the innate immune system also plays a critical role in HDM
      induced allergy pathogenesis. This review will summarize insights into diverse
      determinants that contribute to the HDM allergenicity through the activation of
      innate immunity. In addition to the capacity of mite allergens to directly
      activate mainly skin keratinocytes and airway epithelial cells, innate pattern
      recognition receptor ligands derived from HDM carriers are also involved in the
      development of allergic response by HDM.

PMID- 21196754
TI  - Significant association between IL-17F promoter region polymorphism and
      susceptibility to asthma in a Korean population.
AB  - BACKGROUND: Individual differences in susceptibility to asthma would be expected
      because of common DNA variants of single nucleotide polymorphisms (SNPs) across
      populations. The pro-inflammatory cytokine IL-17F has homology with the IL-17
      motif and induces the expression of other inflammatory cytokines in airway
      epithelial cells. This study aimed to identify IL-17F gene polymorphisms and to
      determine a possible association between these polymorphisms and susceptibility
      to asthma through a case-control study in a Korean population. METHODS: We
      identified SNPs in the IL-17F gene by sequencing. Genotyping was conducted using
      the high-resolution melting (HRM) method on 424 asthma patients and 548 healthy
      controls. RESULTS: The genotype and allele frequencies of rs1889570 SNP were
      significantly different between asthma patients and healthy controls (p = 0.001
      and 0.002, respectively). The rs1889570 SNP genotype was also positively
      associated with the number of peripheral blood eosinophils in asthma patients (p
      = 0.03). The frequencies of haplotypes AA (p = 0.01), GG (p = 0.01) and AG (p =
      0.006) were significantly different between asthma patients and healthy controls.
      CONCLUSIONS: In this study, we confirmed that the rs1889570 polymorphism of the
      IL-17F gene is associated with susceptibility to asthma in a Korean population.

PMID- 21196755
TI  - Non-proteolytic aeroallergens from mites, cat and dog exert adjuvant-like
      activation of bronchial epithelial cells.
AB  - BACKGROUND: Exposure to seasonal or indoor allergens may cause sensitisation and
      development of allergic airway diseases. We have previously demonstrated that the
      non-proteolytic major house dust mite (HDM) allergen Der p 2 stimulates pro
      inflammatory responses in bronchial epithelial cells. We aimed to determine if
      other clinically relevant non-proteolytic aeroallergens originating from HDMs,
      storage mites, cat, dog, birch and timothy also activate respiratory epithelial
      cells. METHODS: Cultures of human bronchial epithelial cell line BEAS-2B, normal
      human bronchial epithelial cells and alveolar epithelial cell line A549 were
      exposed to recombinant (r)Der p 2, natural (n)Der f 2, rEur m 2, rLep d 2, rFel d
      1, nFel d 1, rCan f 2, rBet v 1 or rPhl p 5a. A panel of secreted mediators and
      expression of cell adhesion receptors involved in recruitment, survival and
      adhesion of inflammatory cells in asthmatic airways was assessed. RESULTS: The
      mite allergens rDer p 2, nDer f 2, rEur m 2 and rLep d 2 as well as the cat and
      dog allergens rFel d 1, nFel d 1 and rCan f 2 induced granulocyte colony
      stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin
      (IL)-6, IL-8, monocyte-chemotactic protein-1 and macrophage inflammatory protein
      3alpha secretion from bronchial epithelial cells as well as surface expression of
      intracellular adhesion molecule-1. The pollen allergens rBet v 1 and rPhl p 5a
      from birch and timothy did not activate the cells. None of the studied allergens
      affected the alveolar epithelial cells. CONCLUSION: These results show that both
      mite and structurally unrelated cat and dog allergens can activate respiratory
      epithelial cells by adjuvant-like protease-independent mechanisms.

PMID- 21196756
TI  - Simultaneous stimulation with TGF-beta1 and TNF-alpha induces epithelial
      mesenchymal transition in bronchial epithelial cells.
AB  - BACKGROUND: Airway remodeling is an important feature of chronic airway disease,
      but the mechanisms involved remain unclear. Recently, epithelial mesenchymal
      transition (EMT) was reported to be associated with tissue fibrosis. TGF-beta1,
      which is a potent inducer of EMT, is thought to be related to the pathogenesis of
      airway remodeling. We investigated whether TGF-beta1 and/or TNF-alpha induce EMT
      in bronchial epithelial cells. METHODS: Cultured BEAS-2B cells and primary normal
      human bronchial epithelial cells (NHBE) were treated with TGF-beta1 and/or TNF
      alpha. Morphological changes and the expression of EMT-related markers were
      evaluated by immunocytochemical staining. Expressions of EMT-related markers,
      extracellular matrix (ECM) components (collagen type I and versican), and TGF
      beta receptors I, II, and III were analyzed by quantitative RT-PCR. Migration was
      evaluated using the Boyden chamber technique. RESULTS: The TGF-beta1-induced EMT
      in BEAS-2B cells was demonstrated on the basis of morphological changes and the
      downregulation of E-cadherin. Costimulation with TNF-alpha enhanced the TGF-beta1
      induced morphological changes and increased vimentin expression. Treatment with
      TGF-beta1 increased the expression of collagen type I and versican. EMT induced
      with TGF-beta1 plus TNF-alpha promoted cell migration. Stimulation of NHBE with
      TGF-beta1 led to EMT. CONCLUSION: TGF-beta1 induced EMT in BEAS-2B cells, and
      costimulation with TNF-alpha enhanced the EMT. As a result of the EMT process,
      BEAS-2B cells acquired functions of mesenchymal cells. In addition, TGF-beta1
      treatment induced EMT in NHBE as shown by changes in EMT-related markers.
      Bronchial epithelial cells might contribute to airway remodeling through EMT.

PMID- 21196758
TI  - The efficacy and safety of a Chinese herbal product (Xiao-Feng-San) for the
      treatment of refractory atopic dermatitis: a randomized, double-blind, placebo
      controlled trial.
AB  - BACKGROUND: Severe and widespread atopic dermatitis often fails to respond
      adequately to topical steroids and oral antihistamines and requires
      immunomodulatory drugs which, although effective, have undesirable toxic effects.
      METHODS: In this prospective, randomized, double-blind, placebo-controlled trial,
      71 patients with severe intractable atopic dermatitis were given an 8-week
      treatment with oral Xiao-Feng-San (XFS; 47 patients) or placebo (24 patients).
      Total lesion score, erythema score, surface damage score, pruritus score and
      sleep score were measured at 4-week intervals. RESULTS: Fifty-six patients
      completed both the treatment and follow-up periods. The decrease in the total
      lesion score in the treatment group at 8 weeks was significantly greater than
      that of the placebo group (79.7 +/- 5.8% vs. 13.5 +/- 7.64%; p < 0.001). There
      was also a statistically significant difference between the treatment and placebo
      groups with regard to erythema, surface damage, pruritus and sleep scores. The
      difference between the 2 groups was still significant for all outcome measures
      except the erythema score at the 12-week follow-up, 4 weeks after the 8-week
      treatment had ended. Patients reported no side effects from treatment, although
      some commented on the unpalatability of the medication. CONCLUSION: Our study
      results suggest that the traditional Chinese herbal medicine XFS may be an
      alternative choice of therapy for severe, refractory, extensive and nonexudative
      atopic dermatitis.

PMID- 21196757
TI  - Novel ribbon-type nuclear factor of activated T cells decoy oligodeoxynucleotides
      preclude airways hyperreactivity and Th2 cytokine expression in experimental
      asthma.
AB  - BACKGROUND: Nuclear factor of activated T cells (NFAT) is required for the
      differentiation of Th2 responses, so we examined its role in mouse experimental
      asthma and tested the hypothesis that an NFAT blockade with a decoy against NFAT
      can prevent asthma progression. OBJECTIVE: To determine the effects of the NFAT
      decoy oligodeoxynucleotides (ODNs) on the development of airway inflammation, we
      designed a novel ribbon-type ODN containing two binding sites for NFAT in a
      single decoy molecule without an open end, which is more stable than a
      conventional decoy, and largely preserved its structural integrity in the
      presence of nucleases. METHODS: Ribbon-type NFAT decoy ODNs were transfected into
      ovalbumin (OVA)-sensitized CD3+ T cells in vitro. OVA-immunized mice received
      these cells by intraperitoneal injection. Airway hyperreactivity (AHR) was
      measured and the transfected CD3+ T cells' responses to the airways were
      characterized. RESULTS: Development of AHR after OVA challenge was effectively
      abolished after adoptive transfer of ribbon-type NFAT decoy ODN transfected CD3+
      T cells. Transfer of ribbon-type decoy significantly reduced the number of
      inflammatory cells and the concentrations of IL-4, IL-5 and IL-13, but not IFN
      gamma, in the bronchoalveolar lavage of the recipient mice. CONCLUSION: These
      results suggest the inhibitory effect of ribbon-type decoy ODNs against NFAT on
      the induction of bronchial asthma. Adoptively transferred CD3+ T cells, which are
      transfected with NFAT decoy, may be an effective strategy for the treatment of
      asthma.

PMID- 21196759
TI  - Are IgE levels to foods other than rosaceae predictive of allergy in lipid
      transfer protein-hypersensitive patients?
AB  - BACKGROUND: Lipid transfer protein (LTP), the most frequent cause of primary food
      allergy in Italy, is a cross-reacting plant pan-allergen. Markers able to predict
      whether a patient sensitized to a certain food but not yet clinically allergic
      will develop allergy would be extremely helpful. OBJECTIVE: It was the aim of
      this study to investigate the relevance of IgE levels to some plant foods other
      than Rosaceae as predictors of either local or systemic allergic reaction in LTP
      allergic subjects. METHODS: One hundred (40 males, 60 females , mean age 29
      years) peach-allergic patients monosensitized to LTP seen at 14 Italian centres
      in 2009 were studied. Walnut, hazelnut, peanut, tomato, rice and/or maize allergy
      was ascertained by interview and confirmed by positive skin prick test. IgE
      levels to these foods and to rPru p 3 were measured. RESULTS: Higher levels of
      IgE to Pru p 3 were associated with a higher prevalence of allergy to hazelnut,
      peanut and walnut. For all study foods, except rice, median IgE levels in
      allergic subjects significantly exceeded those in tolerant subjects, though
      within single allergic groups, the differences between patients reporting
      systemic or local (oral) symptoms were not significant. Ninety-five percent cut
      off IgE levels predictive of clinical allergy were established for study foods
      although the marked overlaps between allergic and tolerant subjects made them of
      limited usefulness. CONCLUSION: Specific IgE levels are only partially predictive
      of clinical allergy. The reasons why some individuals showing low specific IgE
      levels develop clinical allergy whereas others showing high IgE levels do not,
      despite similar exposure to the allergen, remain unclear.

PMID- 21196760
TI  - Tolerability of aztreonam in patients with cell-mediated allergy to beta-lactams.
AB  - BACKGROUND: Cross-reactivity between aztreonam and beta-lactams is poor, but
      tolerability of aztreonam has been assessed in a few groups of patients suffering
      from IgE-mediated allergy to beta-lactams. The aim of this study was to assess
      the cross-reactivity of aztreonam with other beta-lactams and its tolerability in
      patients with cell-mediated allergy to these drugs. METHODS: We studied 78
      patients with cell-mediated allergy to beta-lactams who underwent skin prick,
      immediate and delayed-reading intradermal tests as well as patch tests with
      penicilloyl-polylysine, minor determinant mixture, semi-synthetic penicillins,
      cephalosporins, aztreonam and imipenem. Patients with negative allergy testing
      with aztreonam underwent an intramuscular test dosing and were observed for 3 h.
      RESULTS: Our patients experienced 94 non-immediate reactions; delayed-onset
      urticaria (34 cases), maculopapular exanthema (13 cases), urticaria/angioedema
      (15 cases) and itching erythema (13 cases) were the most reported symptoms.
      Amoxicillin (35 cases), ampicillin (28 cases) and bacampicillin (18 cases) were
      the most involved drugs. All patients had a positive patch test and/or a positive
      delayed-reading intradermal test to at least 1 beta-lactam antibiotic and none
      had a positive patch or delayed-reading intradermal test to aztreonam. Then, 65
      patients underwent intramuscular test dosing with aztroenam, and none of them had
      a clinical reaction. CONCLUSIONS: Our data confirm the lack of cross-reactivity
      between beta-lactams and aztreonam in patients with cell-mediated allergy to
      these drugs. Delayed-reading intradermal tests and patch tests with aztreonam
      represent a simple and rapid diagnostic tool to establish tolerability in beta
      lactam-allergic patients.

PMID- 21196761
TI  - Birch pollen honey for birch pollen allergy--a randomized controlled pilot study.
AB  - BACKGROUND: Only a few randomized controlled trials have been carried out to
      evaluate various complementary treatments for allergic disorders. This study
      assessed the effects of the preseasonal use of birch pollen honey (BPH; birch
      pollen added to honey) or regular honey (RH) on symptoms and medication during
      birch pollen season. METHODS: Forty-four patients (59% female, mean age 33 years)
      with physician-diagnosed birch pollen allergy consumed either BPH or RH daily in
      incremental amounts from November 2008 to March 2009. Seventeen patients (53%
      female, mean age 36 years) on their usual allergy medication served as the
      control group. From April to May, patients recorded daily rhinoconjunctival and
      other symptoms and their use of medication. Fifty patients completed the study.
      RESULTS: During birch pollen season in 2009, BPH patients reported a 60% lower
      total symptom score (p < 0.01), twice as many asymptomatic days (p < 0.01), and
      70% fewer days with severe symptoms (p < 0.001), and they used 50% less
      antihistamines (p < 0.001) compared to the control group. The differences between
      the BPH and RH groups were not significant. However, the BPH patients used less
      antihistamines than did the RH patients (p < 0.05). CONCLUSIONS: Patients who
      preseasonally used BPH had significantly better control of their symptoms than
      did those on conventional medication only, and they had marginally better control
      compared to those on RH. The results should be regarded as preliminary, but they
      indicate that BPH could serve as a complementary therapy for birch pollen
      allergy.

PMID- 21196762
TI  - On the occurrence of the diabetes-associated antigen GAD 65 in human sera.
AB  - BACKGROUND: Glutamic acid decarboxylase (GAD 65) is involved as an antigen in
      diabetes mellitus type 1 and is generally considered to be located
      intracellularly in pancreas beta-cells. In this study we demonstrate its
      appearance in 64 human sera samples representing a cross-section of a blood bank.
      METHOD: The proof of GAD 65 in sera was done using an enzyme-linked immunosorbent
      assay (ELISA) setup where it was detected by interaction with corresponding
      antibodies labeled with an enzyme. The enzyme catalyzes a substrate reaction,
      resulting in a change of color, that is used for the quantitative evaluation of
      the antigen-antibody interaction. RESULT: The measurements showed that GAD 65
      exists in various amounts in the sera of blood donors, with an average
      concentration of 58.00 ng/ml. The correlation analysis of samples stored at -80
      degrees  C and at room temperature demonstrates the stability of GAD 65 at room
      temperature. The correlation coefficient between the GAD 65 concentrations of
      samples stored at room temperature and of the same samples after 1 week shows
      that the molecule remains stable. CONCLUSION: Our results encourage us to propose
      antigen GAD 65, due to its frequency in human sera in different concentrations
      and its stability, as a biomarker for the early diagnosis of type 1 diabetes and
      related inflammations.

PMID- 21196763
TI  - Arginine kinase from the cellar spider (Holocnemus pluchei): a new asthma-causing
      allergen.
AB  - BACKGROUND: We report a 31-year-old farmer whose work consists in handling cereal
      and vegetables, who consulted our clinic because of asthma symptoms after
      inhalation of dust during manipulation of the deposited material, usually inside
      the warehouse. METHODS AND RESULTS: Skin prick tests and specific immunoglobulin
      E (IgE) determinations were negative with common aeroallergens. The patient noted
      the presence of many spiders in the warehouse, which were identified as the
      cellar spider Holocnemus pluchei and the common house spider, Tegenaria
      domestica. Extracts of spider bodies brought in by the patient were obtained and
      used to perform in vivo and in vitro studies. Molecular characterization of IgE
      binding bands was performed by mass spectrometry. We obtained positive prick
      tests to the extracts of the bodies of both spiders. Immunoblotting displayed
      different bands in both spider extracts, in a range of 20-70 kDa. All were
      hemocyanins, except for a 17-kDa protein of Holocnemus identified as an arginine
      kinase (AK). Bronchial challenge was positive with the extract of the cellar
      spider and with the AK, but was negative with the domestic house spider.
      CONCLUSION: We present the first case of respiratory allergy due to sensitization
      to AK from a common spider, confirmed by bronchial provocation tests.

PMID- 21196764
TI  - Penicillin determinants in the diagnosis of immediate hypersensitivity reactions
      to beta-lactams.

PMID- 21196765
TI  - Retraction statements. Paper by Gu and Ye [2010;19:105-116].

PMID- 21196766
TI  - Proteinuria thresholds are irrational: a call for proteinuria indexing.
AB  - Current guidelines for chronic kidney disease (CKD) diagnosis, referral and
      management are based on absolute thresholds of proteinuria/albuminuria with no
      reference to the residual nephron mass or function. This is illogical since the
      severity of proteinuria is a direct reflection of the number of filtering
      nephrons as well as their pathology and the capacity of the tubules to reabsorb
      filtered protein/albumin. The current simplistic approach to proteinuria may also
      compromise its usefulness as a robust guide to appropriate treatment, e.g.
      preferential use of inhibitors of the renin-angiotensin-aldosterone system. The
      routine measurement of the urinary protein/albumin:creatinine ratio (PCR/ACR) and
      estimated glomerular filtration rate (eGFR) gives rise to the opportunity to
      index proteinuria for renal function (i.e. a PCR:eGFR or ACR:eGFR ratio). Since
      both PCR/ACR and eGFR are reflections of quantities assessed per unit body
      surface area, this is a logical approach to the assessment of
      proteinuria/albuminuria. We advocate a consideration of the benefits of indexing
      PCR/ACR for eGFR to optimise treatment decisions based on
      proteinuria/albuminuria.

PMID- 21196767
TI  - An appraisal of kidney dysfunction and its risk factors in patients with sickle
      cell disease.
AB  - Sickle cell disease (SCD), a genetically inherited disease of blacks, often
      presents with disabling acute complications which can occasionally be fatal. Its
      renal manifestations are increasingly being recognized as affected patients now
      survive to middle and rarely old age. We set out to determine the magnitude of
      kidney dysfunction in our SCD patient population and evaluate its predictive
      factors. We reviewed the available case records of SCD patients managed in our
      hospital. Information on socio-demographic, clinical and laboratory data were
      retrieved and collated. A total of 374 (99.46%) were reviewed with complete data;
      the median age was 23 years (range 7-62), while median age at diagnosis of SCD
      was 4 years (range 0.25-31). 235 patients (68.2%) had no kidney disease while the
      remaining 139 (37.2%) had proteinuria, hematuria or reduced glomerular filtration
      rate (GFR) <60 ml/min. The age of patients was a significant predictor of kidney
      disease (p = 0.002) and correlated with the level of serum creatinine (r = 0.188,
      p < 0.001), GFR (r = 0.245, p < 0.0001) and the degree of proteinuria (r = 0.174,
      p = 0.006). Patients with kidney disease had a significantly higher number of
      crises/hospitalizations (p < 0.001). Seven patients died in all and 4 (57%) of
      them had end-stage renal disease. We concluded that kidney disease is a common
      complication of SCD and significantly contributes to mortality. The age of the
      patients, duration of SCD and frequency of crises/hospitalizations are strong
      predictors of development of kidney disease.

PMID- 21196768
TI  - 2D-speckle tracking echocardiography contributes to early identification of
      impaired left ventricular myocardial function in patients with chronic kidney
      disease.
AB  - BACKGROUND/AIMS: Our aim was to investigate left ventricular (LV) physiology and
      short-axis and long-axis regional LV myocardial function throughout the cardiac
      cycle with 2D-speckle tracking echocardiography (2D-STE) in patients with chronic
      kidney disease. METHODS: The study population consisted of 40 maintenance
      hemodialysis patients (hemodialysis group), 20 uremic patients hospitalized for
      creation of primary arteriovenous fistula (nondialysis group), and a control
      group of 20 healthy volunteers. LV regional longitudinal, circumferential and
      radial peak systolic velocity (Vs); early diastolic velocity (Ve); and peak
      systolic strain (epsilon) were measured with 2D-STE. RESULTS: Increased LV wall
      thickness and a decreased E/A ratio were found in the nondialysis and
      hemodialysis groups as compared to the control group, but there was no difference
      between the 2 study groups. Longitudinal Vs and Ve of the LV basal segment and
      middle segment in hemodialysis group and nondialysis group were all slower than
      those in the control group, and Vs in the nondialysis group was slower than that
      of the hemodialysis group. Circumferential and radial Vs and Ve were not
      different among the 3 groups, except that the radial Vs of LV basal segment was
      markedly decreased in the nondialysis group. Longitudinal peak systolic strain in
      the hemodialysis and nondialysis groups were both decreased as compared to the
      control group. Circumferential and radial peak systolic strain was decreased only
      in the nondialysis group. CONCLUSIONS: 2D-STE may be used to identify early
      abnormalities in patients with chronic kidney disease who have preserved LV
      ejection fraction. LV regional function appeared to be better in the hemodialysis
      group than that in the nondialysis group.

PMID- 21196769
TI  - The effect of revascularization of atherosclerotic renal artery stenosis on
      coronary flow reserve and peripheral endothelial function.
AB  - BACKGROUND: Patients with atherosclerotic renovascular disease (ARVD) are at
      increased risk of heart disease because of associated hypertension, coronary
      artery disease, cardiac failure and chronic kidney disease. Although suggested to
      be beneficial, the cardiac effects of renal artery revascularization have not
      been well characterized. Our aim was to analyze the effects of percutaneous
      dilatation of renal artery stenosis (RAS) in ARVD patients on coronary and
      peripheral vascular function. METHODS: Nineteen ARVD patients [11 females and 8
      males, age at study entry (mean +/- SD) 69 +/- 10 years] were treated by
      dilatation of unilateral (n = 9) or bilateral (n = 10) RAS, mainly because of
      uncontrolled or refractory hypertension. The patients were studied before and
      after the procedure (103 +/- 29 days). They underwent echocardiography and
      peripheral artery endothelial function testing using flow-mediated dilatation
      (FMD) of brachial artery at rest and during reactive hyperemia. Myocardial blood
      flow was measured using quantitative PET perfusion imaging at baseline and during
      dipyridamole-induced hyperemia. RESULTS: Peripheral endothelial function, tested
      by FMD, as well as systolic blood pressure and left ventricular mass were
      improved in patients with bilateral RAS. However, myocardial perfusion and
      coronary flow reserve (CFR) did not change after the RAS dilatation. CONCLUSION:
      This is the first study to analyze the stage of myocardial perfusion and CFR in
      ARVD patients. Although peripheral endothelial function, systolic blood pressure
      and left ventricular hypertrophy were improved in patients with bilateral RAS by
      revascularization of RAS, it did not have any effect on coronary perfusion.

PMID- 21196770
TI  - Acute oxidative stress following intravenous iron injection in patients on
      chronic hemodialysis: a comparison of iron-sucrose and iron-dextran.
AB  - BACKGROUND/AIMS: Intravascular iron release from parenteral iron formulations can
      catalyze various harmful oxidative reactions. These topics have mainly been
      investigated in vivo with iron-sucrose (IS). The aim of our study was to compare
      IS and iron-dextran (ID) regarding iron release and induction of oxidative
      stress. METHODS: Twenty hemodialysis patients were enrolled. Plasma iron and
      oxidative stress parameters were measured before and 10 min after intravenous
      (IV) injection of 100 mg IS and ID, respectively. RESULTS: Intravascular iron
      increased significantly more after IS. The mean +/- SD changes in plasma iron
      were 314 +/- 172% after IS versus 90 +/- 44% after ID (p < 0.001). Comparable
      changes in non-transferrin bound iron were 86 +/- 42 versus 45 +/- 45%,
      respectively (p < 0.05). Plasma ascorbic free radical did not change following ID
      (-1.8 +/- 11.2%) but increased by 29 +/- 31.3% after IS (p < 0.01). Further,
      protein carbonyls increased following IS (p < 0.05) but not after ID. CONCLUSION:
      Increased oxidative stress was found only after IV injection with IS.

PMID- 21196771
TI  - Right ventricular diastolic function in dialysis patients could be affected by
      vascular access.
AB  - Tricuspid annular plane excursion (TAPSE) measurement in echocardiography is a
      measure of heart diastolic distensibility: a low TAPSE indicates reduced
      ventricular distensibility leading to diastolic dysfunction. It is a good
      prognostic index for cardiac mortality risk in congestive heart failure patients,
      adding significant prognostic information to the NYHA clinical classification.
      Our study was designed to evaluate the effect of a single hemodialysis (HD)
      session on diastolic function and TAPSE, focusing on the effects of vascular
      access typology. Twenty chronically uremic patients (age 51 +/- 10 years,
      dialytic age 24 +/- 8 months), without overt heart disease, underwent
      conventional two-dimensional and Doppler echocardiography immediately before
      starting and 15 min after ending a mid-week HD session. Ten patients had distal
      radiocephalic arterovenous fistula (AVF), and 10 had permanent central venous
      catheters (CVC). The amount of fluid removed by HD was 2,706 +/- 1,047 g/session.
      HD led to a reduction in TAPSE, left ventricle end-diastole volume, left
      ventricle end-systole volume, right ventricle end-diastole diameter, peak early
      transmitral flow velocity, and the ratio of early to late Doppler velocities of
      diastolic mitral flow. AVF patients showed greater right ventricle diameters
      versus CVC patients, while TAPSE appeared higher in the latter. Only the AVF
      patient group showed TAPSE values <15 mm. Our data confirm the effects of
      terminal uremia on right ventricle function (chamber dilation, impaired diastolic
      function), showing that these abnormalities are more frequent in AVF patients as
      opposed to CVC patients. It is reasonable to explain these clinical features as
      the effect of preload increase operated by AVF.

PMID- 21196772
TI  - Patterns of mind-body therapies in adults with common neurological conditions.
AB  - BACKGROUND: Over 40% of adults with common neurological conditions use
      complementary and alternative medicine, and mind-body therapies are the most
      commonly used form. Our objective was to describe mind-body use in adults with
      common neurological conditions. METHODS: We compared mind-body use between adults
      with and without common neurological conditions (regular headaches, migraines,
      back pain with sciatica, strokes, dementia, seizures or memory loss) using the
      2007 National Health Interview Survey of 23,393 sampled American adults. RESULTS:
      Adults with common neurological conditions used mind-body therapies more
      frequently than those without (24.5 vs. 16.6%, p < 0.0001); differences persisted
      after adjustment. Deep breathing exercises, meditation and yoga were used most
      frequently. Nearly 70% of the adults with common neurological conditions did not
      discuss their mind-body use with their health care provider. Those with
      neurological conditions used mind-body therapies more than those without these
      conditions because of provider recommendation (26 vs. 13%) or because
      conventional treatments were perceived ineffective (12 vs. 4%) or too costly (7
      vs. 2%), respectively. CONCLUSIONS: Mind-body therapies are used more frequently
      among adults with common neurological conditions, more often when conventional
      treatments were perceived ineffective. More research is warranted on the efficacy
      of mind-body use for common neurological conditions.

PMID- 21196773
TI  - The Danish Alzheimer intervention study: rationale, study design and baseline
      characteristics of the cohort.
AB  - BACKGROUND: There is a lack of appropriately designed trials investigating the
      efficacy of psychosocial interventions for patients with mild dementia and their
      family caregivers. This paper reports the rationale and design of the Danish
      Alzheimer Disease Intervention Study and baseline characteristics of the cohort.
      METHODS: The study was a 1-year multicentre randomized controlled rater-blinded
      trial with randomization to follow-up and a multifaceted semitailored
      intervention programme or to follow-up only (with extension of follow-up to 3
      years). The intervention included a counselling programme, teaching courses,
      written information and logbooks. The outcomes included clinical efficacy
      parameters, patient satisfaction and health economic consequences. RESULTS: A
      total of 330 patients and their 330 caregivers were included during a period of
      18 months. The majority (65.2 %) of the caregivers were spouses. At inclusion the
      mean age of the patients and caregivers was 76.2 and 66.0 years, respectively.
      CONCLUSION: The study will explore the added value of a multifaceted intervention
      programme and contribute to the design of future interventions for patients with
      mild dementia and their caregivers.

PMID- 21196774
TI  - Characterisation of the human ADAM15 promoter.
AB  - BACKGROUND: ADAM15 is a membrane-bound member of the adamalysin family that is up
      regulated in areas of tissue remodelling. Previous studies have demonstrated the
      role of ADAM15 in mesangial cell migration, which is integral in tissue
      remodelling in pathology and repair. The current study was designed to identify
      and analyse the genomic regions upstream of ADAM15 that would regulate its
      transcription. METHODS: Using 5'-RACE and RT-PCR, the ADAM15 5'-UTR was extended
      and luciferase constructs assembled to examine the transcription start site and
      characterise the promoter region of this gene. RESULTS: A 145-bp proximal
      promoter construct showed full activity in unstimulated cells. Analysis of this
      region identified three potential Sp1-binding sites. Electromobility and
      supershift assays confirmed that Sp1 was constitutively present in MC nuclei.
      Mutations in each Sp1 site confirmed each was needed for full activity, while
      mutation of all three sites abrogated luciferase activity demonstrating that Sp1
      was involved in the promoter activity of ADAM15. Methylation of this promoter
      fragment abolished the activity, while the methyltransferase inhibitor 5-aza-3'
      deoxycytidine showed no increased activity in transfected cells, implying that
      the promoter was not methylated in our cells. CONCLUSION: These results
      demonstrate the intrinsic promoter activity of ADAM15 in quiescent MC and show
      the involvement of Sp1 in its regulation.

PMID- 21196776
TI  - Effect of antenatal corticosteroid treatment on lung function in full-term
      newborn infants.
AB  - BACKGROUND: Antenatal treatment of pregnant women with corticosteroids in order
      to stimulate surfactant production has been shown to be effective. However, lung
      structure is also affected by the treatment. OBJECTIVE: We tested the hypothesis
      that changes within lung acini, induced by maternal corticosteroid treatment,
      persist during lung development. METHODS: Twenty-two healthy infants, whose
      mothers were treated with up to three doses of betamethasone at 25-33 weeks of
      pregnancy because of preterm labour, but where labour terminated and the infants
      were born at term, were studied at term and compared to a group of 50 healthy
      newborn infants without prenatal treatment with corticosteroids. Gas-mixing
      efficiency was measured in terms of moment ratio with a nitrogen washout method
      together with functional residual capacity. Mechanical parameters were assessed
      with the single occlusion technique. RESULTS: There were no signs of disturbed
      gas mixing or changed lung volume or mechanics in the treated group. CONCLUSION:
      The result contributes to an emerging body of evidence that antenatal treatment
      with corticosteroids does not permanently affect lung structure or function.

PMID- 21196775
TI  - Glomerular podocytes express type 1 adenylate cyclase: inactivation results in
      susceptibility to proteinuria.
AB  - BACKGROUND/AIMS: The organization of actin cytoskeleton in podocyte foot
      processes plays a critical role in the maintenance of the glomerular filtration
      barrier. The cAMP pathway is an important regulator of the actin network assembly
      in cells. However, the role of the cAMP pathway in podocytes is not well
      understood. Type 1 adenylate cyclase (Adcy1), previously thought to be specific
      for neuronal tissue, is a member of the family of enzymes that catalyses the
      formation of cAMP. In this study, we characterized the expression and role of
      Adcy1 in the kidney. METHODS: Expression of Adcy1 was studied by RT-PCR, Northern
      blotting and in situ hybridization. The role of Adcy1 in podocytes was
      investigated by analyzing Adcy1 knockout mice (Adcy1-/-). RESULTS AND CONCLUSION:
      Adcy1 is expressed in the kidney specifically by podocytes. In the kidney, Adcy1
      does not have a critical role in normal physiological functioning as kidney
      histology and function are normal in Adcy1-/- mice. However, albumin overload
      resulted in severe albuminuria in Adcy1-/- mice, whereas wild-type control mice
      showed only mild albumin leakage to urine. In conclusion, we have identified
      Adcy1 as a novel podocyte signaling protein that seems to have a role in
      compensatory physiological processes in the glomerulus.

PMID- 21196777
TI  - Di-nucleotide repeat polymorphisms of the insulin-like growth factor-1 gene and
      their association with IGF-1, insulin-like growth factor-binding protein-1 and
      birth size in a Sri-Lankan cohort.
AB  - BACKGROUND: Insulin-like growth factor (IGF)-I is implicated in fetal growth.
      Ethnic variations of IGF-1 have also been suggested. Di-nucleotide repeat
      polymorphisms of the IGF-1 gene or their association with IGF-1 levels and birth
      size have not been studied in Sri Lankans. OBJECTIVES: To describe IGF-1 di
      nucleotide repeat polymorphisms and their association with IGF-1 and IGF-binding
      protein (IGFBP)-1 levels and birth size in a cohort of Sri Lankans. METHODS: A
      cross-sectional study on 200 mother-newborn pairs was carried out. Maternal and
      cord blood levels of IGF-1 and IGFBP-1 were measured by enzyme-linked
      immunosorbent assay. Three di-nucleotide repeat polymorphisms of the IGF-1 gene
      [cytosine-adenine (CA) repeats in the promoter and 3' regions and intron 2
      cytosine-thymine (CT) repeat] were studied using PCR amplification and fragment
      analysis. RESULTS: Cord blood IGFBP-1 levels correlated negatively with birth
      weight (p < 0.01) and crown-heel length (p < 0.05). Wild-type alleles of the CA
      repeat polymorphisms differed from those reported in other populations. Newborn
      and maternal intron 2 CT repeat polymorphism showed a significant effect on birth
      weight (p < 0.01 and p < 0.001, respectively), crown-heel length (p < 0.01) and
      head circumference (p < 0.01 and p < 0.05, respectively). Promoter region CA
      repeat polymorphism and intron 2 CT repeat polymorphism in the newborns were
      significantly (p < 0.05) associated with cord blood IGF-1 levels. Almost all
      these effects were limited to primiparous pregnancies. CONCLUSIONS: In Sri
      Lankans intron 2 CT repeat polymorphism of the IGF-1 gene appears to be a
      significant contributor to IGF-1 levels and birth size in primiparous
      pregnancies.

PMID- 21196778
TI  - Hyponatremia and inflammation: the emerging role of interleukin-6 in
      osmoregulation.
AB  - Although hyponatremia is a recognized complication of several inflammatory
      diseases, its pathophysiology in this setting has remained elusive until
      recently. A growing body of evidence now points to an important role for
      interleukin-6 in the non-osmotic release of vasopressin. Here, we review this
      evidence by exploring the immuno-neuroendocrine pathways connecting interleukin-6
      with vasopressin. The importance of these connections extends to several clinical
      scenarios of hyponatremia and inflammation, including hospital-acquired
      hyponatremia, postoperative hyponatremia, exercise-associated hyponatremia, and
      hyponatremia in the elderly. Besides insights in pathophysiology, the recognition
      of the propensity for antidiuresis during inflammation is also important with
      regard to monitoring patients and selecting the appropriate intravenous fluid
      regimen, for which recommendations are provided.

PMID- 21196779
TI  - Identification of a novel WNK4 mutation in Chinese patients with
      pseudohypoaldosteronism type II.
AB  - BACKGROUND: It has been reported that mutations in WNK1 and WNK4 cause
      pseudohypoaldosteronism type II (PHA2), an autosomal dominant renal disease. WNK
      kinase proteins are expressed in the kidney and regulate ion transport including
      the thiazide-sensitive sodium chloride cotransporter (NCC). In this report, we
      screened 4 Chinese PHA2 pedigrees for WNK4 mutations, identified a novel
      mutation, and studied its effects on NCC protein trafficking in vitro. METHODS:
      The patients' genomic DNA was extracted from peripheral leukocytes. Sequence
      analysis was performed by PCR amplification of the 19 exons of WNK4. The wild
      type or mutant WNK4 was coexpressed with NCC in HEK293 cells. We measured the
      effect of wild-type WNK4 compared to the mutant WNK4 on NCC protein surface
      expression. RESULTS: A novel missense mutation in WNK4, K1169E, was identified in
      1 of the 4 pedigrees. Analysis of confocal images showed that K1169E lost its
      inhibitory effect on NCC surface expression compared to wild-type WNK4 when
      expressed in HEK293 cells, while it did not change NCC total protein expression.
      CONCLUSIONS: We identified an unreported disease-causing WNK4 missense mutation,
      K1169E, in 1 Chinese PHA2 pedigree. This mutation appears to be a 'loss of
      function' of NCC inhibition and suggests that some important functional roles lie
      in the 2nd coiled-coil domain of WNK4.

PMID- 21196780
TI  - Serotonin transporter bi- and triallelic genotypes and their relationship with
      anxiety and academic performance: a preliminary study.
AB  - BACKGROUND: Considerable evidence suggests that variation of the serotonin
      transporter-linked promoter region (5- HTTLPR) is associated with anxiety-related
      traits. Academic outcomes are also more closely related to trait anxiety. This
      preliminary study aimed to explore the association between academic performance
      and levels of anxiety with respect to the bi- and triallelic classification of 5
      HTTLPR polymorphism of the 5-HTT gene in teacher candidates. METHODS: In our
      study, Spielberger's State-Trait Anxiety Inventory, the Selection Examination for
      Professional Posts in Public Organizations (KPSS) and 5-HTTLPR genotypes were
      used to investigate a group of 94 healthy teacher candidates. RESULTS: Higher
      anxiety scores were significantly associated with the S'S' genotype. There was no
      direct, statistically significant association between academic performance and
      genotypic groups regarding bi- and triallelic classification. However, the
      students who have L'L' or LL genotypes had the lowest levels of trait anxiety and
      the poorest academic performance. Additionally, there was a significant positive
      correlation between academic performance and anxiety levels. DISCUSSION: These
      findings support the idea that S and L(G) alleles are associated with anxiety
      related traits, and that the S'S' genotype may be a good indicator for anxiety
      related traits in a sample from the Turkish population. A specific degree of
      anxiety is considered to be a motivation for learning and high academic
      performance. However, 5-HTTLPR polymorphism of the 5-HTT gene may be one of the
      genetic factors affecting academic performance in connection with anxiety levels.
      Implications for incorporating anxiety management training in the educational
      process in terms of both environmental and individual factors will have a very
      important role in improving effective strategies for student personality
      services, as well as for development and planning.

PMID- 21196781
TI  - Neural correlates of belief-laden reasoning during premise processing: an event
      related potential study.
AB  - In this study, electrophysiological correlates of belief-laden reasoning were
      investigated. As subjects, trained participants were required to draw a logical
      conclusion after being exposed to 4 conditional arguments: the inhibitory content
      of modus tollens (ICMT), facilitatory content of modus tollens (FCMT), inhibitory
      content of denial of the antecedent (ICDA) and facilitatory content of denial of
      the antecedent (FCDA). Event-related potentials were employed to record the
      processing of minor premises. The results show that in comparison with FCMT, a
      greater negativity in the ICMT developed during both the 400- to 600- and the 800
      to 1,600-ms time windows. A greater anterior cingulate cortex activity observed
      in the 800- to 1,600-ms time window in ICMT could reflect a detection of the
      conflict between empirical beliefs and logical rules. However, the components
      elicited by ICDA and FCDA were not significantly different. The results indicate
      that logical training influenced MT and DA forms of belief-laden reasoning in
      different ways and different strategies were likely adopted in the inference
      processes.

PMID- 21196782
TI  - Neural substrates of affective face recognition in alexithymia: a functional
      magnetic resonance imaging study.
AB  - BACKGROUND: Alexithymia is a condition characterized by deficits in cognitive
      processing and the regulation of emotions. Several theories have been proposed
      for the underlying neurobiology, but the etiology of alexithymia remains unclear.
      METHODS: Using functional magnetic resonance imaging, we investigated brain
      activation measured on the scale of alexithymia in 38 individuals who were
      presented with neutral, sad, or angry affective facial stimuli. RESULTS: We found
      significant inverse correlations between the degree of alexithymia represented by
      the Korean version of the Toronto Alexithymia Scale (TAS-20K) and the intensity
      of the neural response to angry facial stimuli over neutral facial stimuli in the
      right caudate. This result was mainly due to the activations in factor 2
      (difficulty describing feelings) in TAS-20K scale. CONCLUSIONS: The results
      suggest that functional impairments in the caudate of the fronto-striatal
      circuitry may play important roles in the pathophysiology of alexithymia.

PMID- 21196783
TI  - Lack of association between testosterone and suicide attempts.
AB  - OBJECTIVE: To determine whether testosterone levels differ in male suicide
      attempters versus healthy controls and to explore the associations between
      testosterone levels and time of blood collection, and between testosterone levels
      and characteristics of suicide attempts. METHOD: A sample of 112 male suicide
      attempters was studied. Thirty-seven male blood donors were recruited as
      controls. RESULTS: The mean testosterone levels were 5.1 +/- 2.9 ng/ml in male
      attempters and 4.6 +/- 1.6 ng/ml in controls. Group differences in testosterone
      levels were not significant when we studied the interaction with time of
      extraction (F = 0.37; d.f. = 2; p = 0.70) or when matched by age and time of
      extraction (t = -0.74; d.f. = 26; p = 0.47). When partial correlations were
      performed correcting for the effect of time of extraction, significant partial
      correlations were found in testosterone levels with history of aggressive
      behavior and lethality of the attempt. CONCLUSIONS: When circadian variation and
      age were considered, we found no support for the putative role of testosterone as
      a biological marker of suicidal behavior. Further research should consider: (1)
      testosterone and neurosteroids; (2) serial determinations with a minimal time gap
      between the attempt and the blood extraction; (3) controls within the same time
      periods, and (4) other variables that may affect testosterone levels, such as
      body mass index, physical activity and sleep disturbances.

PMID- 21196784
TI  - The greater dimensions of obesity.

PMID- 21196785
TI  - Putting the greater dimensions of obesity into perspective.

PMID- 21196786
TI  - Contents of this issue.

PMID- 21196787
TI  - Coffee, tea and their additives: association with BMI and waist circumference.
AB  - OBJECTIVE: The purposes of this study were to perform a detailed analysis how: i)
      the frequency of coffee/tea consumption and ii) the use of additives in
      coffee/tea is associated with measures of total and abdominal obesity. METHOD:
      3,823 participants of the 2003-2004 National Health and Nutrition Examination
      Survey were examined. Obesity was assessed by BMI and waist circumference (WC).
      Coffee and tea consumption and use of additives were assessed by questionnaire.
      RESULTS: Coffee consumption was not related to BMI or WC in either gender.
      However, men who drank >=2 cups of tea per day had lower BMI (25.9 vs. 28.0
      kg/m(2)) and WC (95.2 vs. 101.32 cm) values than men who never drank drink tea (p
      <= 0.05). The associations between tea consumption and BMI or WC were no longer
      significant after adjustment for additive use. Coffee/tea drinkers who used
      artificial sweeteners had larger (p <= 0.05) BMIs than coffee/tea drinkers who
      did not use sweeteners (28.2 vs. 27.1 kg/m(2) in men, 28.4 vs. 27.1 kg/m(2) in
      women). CONCLUSION: Frequency of coffee/tea consumption was not associated with
      measures of obesity because additive use explained the association between tea
      consumption and obesity in men. Artificial sweetener use within coffee/tea was
      associated with higher BMI.

PMID- 21196788
TI  - Use of causal language in observational studies of obesity and nutrition.
AB  - OBJECTIVE: To assess the inappropriate use of causal language in studies on
      obesity and nutrition. METHODS: Titles and abstracts of 525 peer-reviewed papers
      in the 4 leading journals in the fields of obesity and nutrition were scrutinized
      for language implying causality in observational studies published in 2006.
      RESULTS: Such misleading language appeared in 161 papers (31%) independent of
      funding source. Remarkably 49% of studies lacking statistically significant
      primary outcomes used misleading language compared to 29% of those with p values
      <=0.05 (chi square p < 0.001). Exculpatory language was present in the body of
      the text in 19%; of the 161 studies. CONCLUSION: We suggest that editors and
      reviewers evaluate submissions for misleading reporting.

PMID- 21196789
TI  - Air displacement plethysmography for estimating body composition changes with
      weight loss in middle-aged Japanese men.
AB  - AIM: To examine the degree to which air displacement plethysmography (ADP) can
      track body composition changes in response to weight loss in obese Japanese men.
      METHOD: 50 men, aged 30-65 years with a mean BMI of 30 kg/m(2), were included in
      a 3-month weight loss program. Percentage of fat mass (%FM) was determined by
      dual energy X-ray absorptiometry (DXA) and ADP at baseline and month 3. RESULTS:
      With 6.2 +/- 4.3 kg of weight loss, %FM, as determined by DXA and ADP,
      significantly decreased by 3.9 +/- 2.9% and 3.9 +/- 3.3% respectively. There was
      no mean difference for change (Delta) in %FM between the two methods. DXA-derived
      Delta%FM significantly correlated with Delta%FM determined by ADP (R(2) = 0.48, p
      < 0.01). Furthermore, the Bland-Altman plots demonstrated no systematic bias for
      Delta%FM (r = -0.20, p = 0.17). However, %FM by ADP (r = 0.42) at baseline and
      Delta%FM by ADP (r = -0.54) were significantly correlated to the differences
      between Delta%FM by DXA and ADP. CONCLUSION: These results suggest that ADP is
      comparably accurate for evaluating Delta%FM when compared with DXA, although
      there were proportional biases.

PMID- 21196790
TI  - Association between obesity and unintentional injury in older adults.
AB  - OBJECTIVE: To test the association between obesity and specific types and
      anatomical sites of unintentional injuries in older adults. METHODS: Participants
      consisted of 52,857 men and women aged >=65 years from the 2003 and 2005 Canadian
      Community Health Survey. Weight, height, and details on injuries occurring in the
      past year were obtained by survey. RESULTS: Obese individuals had a higher risk
      for sprains/strains occurring at any anatomical site (odds ratio, 95% confidence
      interval: men 1.48, 1.48-1.62; women 1.14, 1.10-1.27). Conversely, obese
      individuals were less likely to have a fracture at any anatomical location (men
      0.56, 0.50-0.63; women 0.66, 0.51-0.92) or at the hip (men 0.31, 0.12-0.53; women
      0.42, 0.29-0.92). Finally, obese older adults did not experience more superficial
      injuries than normal-weight individuals. CONCLUSION: Among this large sample of
      older adults, obesity provided some protection against fractures but was
      associated with higher odds for sprains/strains.

PMID- 21196791
TI  - Reduced respiratory capacity in muscle mitochondria of obese subjects.
AB  - BACKGROUND/AIMS: The extent of weight gain varies among individuals despite equal
      calorie overconsumption. Furthermore, weight gain is often less than expected
      from energy excess. This suggests differences in metabolic efficiency and basal
      metabolism. Since mitochondrial uncoupling accounts for a substantial portion of
      the basal metabolic rate, we compared skeletal muscle mitochondrial respiration
      in obese subjects to normal-weight reference groups with various degrees of
      physical activity. METHODS: Muscle biopsies were taken from the vastus lateralis
      muscle of 9 healthy obese subjects (BMI 40 +/- 3). Mitochondria were isolated and
      analyzed for coupled (state 3) and uncoupled (state 4) respirations as well as
      mitochondrial efficiency (P/O ratio) using pyruvate as a substrate. Respiratory
      data were compared to reference groups A, normal-weight untrained (BMI 24 +/-
      0.7), and B, normal-weight trained (BMI 24 +/- 0.6). RESULTS: Obese subjects had
      a decreased respiratory capacity per mitochondrial volume compared to the
      reference groups: this was evident in state 4 (65% and 35% of reference group A
      and B, respectively) and state 3 (53% and 29% of A and B, respectively) (p <
      0.05). CONCLUSION: Obese subjects had a low capacity for fuel oxidation, which
      may play a role in the predisposition of obesity. However, whether lower
      mitochondrial capacity is a cause or a consequence of obesity requires further
      research.

PMID- 21196792
TI  - Behavioural interventions for obese adults with additional risk factors for
      morbidity: systematic review of effects on behaviour, weight and disease risk
      factors.
AB  - BACKGROUND: Reducing obesity through effective behaviour change interventions is
      of key importance to prevent disabling and life-threatening conditions,
      particularly in individuals already at risk for morbidity. PURPOSE: To assess the
      effects of behavioural interventions for obese adults with additional risk
      factors for morbidity on behaviour, weight and disease risk factors. METHODS:
      Systematic review of randomised controlled trials (RCTs). Three electronic
      databases and three journals were searched for behavioural interventions (aimed
      at changing dietary intake and/or physical activity (PA)) for adults (mean BMI
      >=30 kg/m(2); mean age >=40 years) with risk factors for morbidity, reporting
      follow-up data >=12 weeks. RESULTS: 44 RCTs met the inclusion criteria.
      Behavioural outcomes, weight loss, and cardiovascular disease risk factors showed
      consistent modest improvements over time, especially for interventions targeting
      both diet and PA. CONCLUSION: Behavioural interventions in at-risk populations
      showed positive effect tendencies on behaviour, weight, and disease risk factors.
      However, there is still ample room for improvement, and future research should
      focus on identifying the most effective means of inducing dietary and PA
      behaviour change in this vulnerable population.

PMID- 21196793
TI  - Sigma1 receptor antagonist BD1047 enhances reversal of conditioned place
      preference from cocaine to social interaction.
AB  - We have previously shown that only four 15-min social interaction episodes with a
      male adult conspecific reversed cocaine conditioned place preference (CPP) even
      despite continuing CPP training with cocaine. In the present study, we
      investigated if BD1047, a sigma1 receptor antagonist that has been shown to
      inhibit the expression of cocaine CPP, is able to enhance this effect. BD1047,
      given as a 10-min pretreatment, dose-dependently (ED50 of 0.0036 mg/kg i.p.)
      decreased the time spent in the previously cocaine-associated compartment in
      favour of the time spent in the compartment in which a single social interaction
      had taken place. Our findings indicate that sigma1 blockade may be used
      therapeutically to enhance treatment adherence in social interaction-based
      rehabilitation programs.

PMID- 21196794
TI  - Iniencephaly: clinical, radiological and surgical findings.
AB  - The authors report a case of iniencephaly in a 6-year-old boy with a huge
      occipital bone defect and encephalocele, extensive spina bifida of the cervical
      vertebrae and fixed retroflexion of the head due to Sprengel's deformity. He
      presented with some cerebellar and cranial nerve symptoms and new episodes of
      neck pain and drop attacks. Brain imaging confirmed progressive deformity of the
      brain stem, cerebellar herniation into the encephalocele sac and
      ventriculomegaly. Surgical repair of the encephalocele was performed with
      preservation of all herniated cerebellar tissue and the release of thick
      arachnoid adhesions to make more space to return the herniated neural tissue from
      the sac to the cranium. The patient was found to have progressive facial palsy
      and intracranial hypertension 3 days after surgery, which improved with
      ventriculoperitoneal shunting. Iniencephaly is generally a fatal anomaly, and
      only 7 such patients have been reported to have survived. Because of the fatality
      of this anomaly, prenatal diagnosis of iniencephly and pregnancy termination are
      important. The patient presented herein is only the second patient with
      iniencephaly and encephalocele to be operated on. The severity of associated
      systemic and cranial abnormalities is fundamental with regard to survival.
      Essential points for surgery are preparing enough space to save herniated
      functional neural tissues, management of associated hydrocephalus and brain stem
      rotation/compression due to decreased postoperative space. In the surviving
      child, early correction of Sprengel's deformity would provide a better aesthetic
      position of the neck with preservation of brachial plexus integrity.

PMID- 21196795
TI  - Progressive biological behavior of a dysembryoplastic neuroepithelial tumor.
AB  - We present the case of a 13-month-old girl with a right occipital cortical
      alteration on MRI that proved to be a growing lesion. Tumor growth had been
      observed over a period of 15 months before total resection was performed,
      revealing a dysembryoplastic neuroepithelial tumor WHO grade I. This case shows
      that dysembryoplastic neuroepithelial tumors can present as growing neoplasias.
      It underlines the importance of obtaining histologic diagnosis and close follow
      up examinations using MRI, even in so-called stable lesions that are only
      unveiling through epileptic seizures.

PMID- 21196796
TI  - A unique pattern of intracranial pressure in a patient with traumatic paroxysmal
      sympathetic storm.
AB  - Paroxysmal sympathetic storm (PSS), or diencephalic seizure, usually appears in
      patients with severe traumatic brain injury and is characterized by various
      sympathetic symptoms. The physiological effects of this syndrome are not well
      studied. The authors monitored intracranial pressure (ICP) in a patient with PSS
      and reviewed its impact on the physiology and management of the syndrome. A 12
      year-old male patient was involved in a traffic accident. Upon arrival at the
      emergency room, his Glasgow Coma Scale score was 5 and he showed decerebration. A
      brain CT showed an intracerebral hematoma in the right basal ganglia, at which
      point craniotomy and removal of the hematoma were performed. Continuous
      intracranial monitoring was performed using the fiber-optic intraparenchymal
      method. Beginning the day after the trauma, the patient began exhibiting
      sympathetic symptoms including intermittent episodes of fever, tachycardia,
      increased blood pressure, tachypnea, diaphoresis and decerebrate rigidity. These
      episodes were accompanied by ICP elevation of greater than 20 mm Hg. ICP was
      decreased during hyperventilation, and the episodic symptoms subsided as ICP
      normalized. PaCO(2) was periodically altered in association with
      hyperventilation. Electroencephalogram did not show epileptiform discharges, and
      the sympathetic spells were aborted by continuous intravenous midazolam infusion.
      The authors report on a pattern of ICP monitoring in association with PSS.
      Traumatic PSS should be recognized in the appropriate setting to prevent
      secondary brain damage.

PMID- 21196797
TI  - Incidental resolution of a radiation-induced cavernous hemangioma of the brain
      following the use of bevacizumab in a child with recurrent medulloblastoma.
AB  - Radiation-induced cavernous hemangiomas (RICH) are a known complication of
      radiation exposure, especially in young children. The current treatment
      approaches to these lesions include observation and surgical resection. We report
      the case of a 4-year-old male with recurrent medulloblastoma who had resolution
      of an incidental RICH lesion while being treated with bevacizumab for his
      recurrent brain tumor. There was no evidence of worsening hemorrhage with this
      therapy and the RICH did not recur upon discontinuation of the chemotherapy
      regimen. This is the first documented case of a RICH lesion responding to
      antiangiogenic therapy, suggesting the possible use of this class of agents in
      the treatment of symptomatic patients who are not considered appropriate
      candidates for surgical resection. Although the risk of bleeding must be taken
      into consideration, antiangiogenic therapies have the potential to be a novel
      treatment modality for symptomatic RICH lesions.

PMID- 21196798
TI  - Aneurysmal bone cyst of the petrous bone: case presentation and review of the
      literature.
AB  - Aneurysmal bone cysts (ABC) were originally described by Jaffe and Lichtenstein
      [Arch Surg 1942;44:1004-1025] in 1942 as nonneoplastic benign lesions with
      obscure pathogenesis. ABC occurring in the temporal bone are uncommon. Those
      arising from the petrous portion of the temporal bone are exceedingly rare. We
      report a right petrous ABC in a 16-year-old girl who presented clinically with
      hearing loss, facial weakness, and facial numbness and tingling. Her symptoms
      were preceded by a coincidental traumatic concussion 4 months earlier.
      Preoperative magnetic resonance imaging and computed tomography findings were
      both consistent with an ABC, although the lesion was noted to be in a very
      unusual location. Surgical resection was performed with adjuvant preoperative
      embolization. The patient recovered complete facial sensation and movement, and
      follow-up imaging documented complete resection.

PMID- 21196799
TI  - Reorganization of sensorimotor function after functional hemispherectomy studied
      using near-infrared spectroscopy.
AB  - Hemimegalencephaly is a rare congenital disease that occurs with intractable
      epilepsy and is a childhood developmental disorder. A functional hemispherectomy
      is indicated for the treatment of hemimegalencephaly with intractable epilepsy.
      We present a case of hemimegalencephaly in a 6-month-old male. After
      hemispherectomy, his seizures disappeared completely and postoperative
      neurological examination showed right hemiplegia. His right arm and limb function
      were recovered gradually by rehabilitation with passive movement. We investigated
      cortical activation using near-infrared spectroscopy (NIRS). Serial NIRS showed
      right cortical activation by passive movement of his right arm. We suggest that
      NIRS showed the ipsilateral reorganization process as an effect of
      neurorehabilitation for disconnection of the brain.

PMID- 21196800
TI  - Osmotic myelinolysis with malignant cerebellar edema occurring after DDAVP
      induced hyponatremia in a child.
AB  - Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) are dire
      neurological disorders, characterized by severe damage to the myelin sheath of
      neurons, which typically result from rapid correction or overcorrection of
      systemic hyponatremia. For many years, both conditions have been considered
      universally fatal, though survivors have been reported more recently. Pediatric
      cases are rare. We present a 13-year-old boy with panhypopituitarism secondary to
      repair of a nasofrontal encephalocele in infancy, managed on long-term
      corticosteroid, deamino arginine vasopressin and thyroid hormone. He presented
      with severe hyponatremia (116 mEq/l), which during correction rapidly and
      unexpectedly increased to 176 mEq/l, resulting in profoundly impaired
      consciousness. Brain imaging revealed multiple bilateral changes in the basal
      ganglia, thalamus, pons and cerebral white matter, consistent with both CPM and
      EPM. Malignant cerebellar edema necessitated emergent suboccipital craniectomy,
      with subsequent improvement in level of consciousness and imaging
      postoperatively. However, he succumbed to acute cardiorespiratory arrest 8 weeks
      later. Nine similar cases from the literature are reviewed.

PMID- 21196801
TI  - Rare case of giant temporal cavernous angioma in a child.

PMID- 21196802
TI  - Primary diffuse leptomeningeal oligodendroglioma.

PMID- 21196803
TI  - New directions in treatment research for personality disorders: effectiveness of
      different levels of care.

PMID- 21196804
TI  - Does the therapeutic relationship predict outcomes of psychiatric treatment in
      patients with psychosis? A systematic review.
AB  - BACKGROUND: Numerous studies have shown that the quality of the therapeutic
      relationship (TR) between the patient and the clinician is an important predictor
      of the outcome of different forms of psychotherapy. It is less clear whether the
      TR also predicts outcomes of psychiatric treatment programmes in patients with
      psychosis (i.e. outside conventional psychotherapy). METHODS: We conducted a
      systematic review and identified 9 primary studies that prospectively tested the
      association of the TR with 3 outcomes, i.e. hospitalisation, symptom levels and
      functioning. Because of the heterogeneity of the methods used, a meta-analysis
      was not feasible. A vote counting method was used to determine the number of
      statistically significant effects in the hypothesised direction (i.e. that a more
      positive TR predicts more favourable outcomes). RESULTS: For each outcome, a chi2
      analysis showed that the number of statistically significant findings in the
      hypothesised direction was greater than expected if the null hypothesis of no
      association were true. However, studies had methodological shortcomings, and the
      effect sizes of positive associations were rather small. CONCLUSION: It may be
      concluded that there is some, but not overwhelming, evidence that the TR predicts
      outcomes of complex psychiatric treatment programmes in patients with psychosis,
      and that methodologically more rigorous research is required. Such research
      should measure the TR at initial stages of treatment and use validated assessment
      instruments for both TR and outcomes.

PMID- 21196805
TI  - Health effects on leaders and co-workers of an art-based leadership development
      program.
AB  - BACKGROUND: There are very few evaluations of the effectiveness of leadership
      development programs. The purpose of the study was to examine whether an art
      based leadership program may have a more beneficial effect than a conventional
      one on leaders' and their corresponding subordinates' mental and biological
      stress. METHODS: Participating leaders were randomized to 2 year-long leadership
      programs, 1 art-based and 1 conventional, with follow-up of the leaders and their
      subordinates at 12 and 18 months. The art-based program built on an experimental
      theatre form, a collage of literary text and music, followed by writing and
      discussions focused on existential and ethical problems. RESULTS: After 18 months
      a pattern was clearly visible with advantage for the art-based group. In the art
      group (leaders and their subordinates together as well as for subordinates only)
      compared to the conventional group, there was a significant improvement of mental
      health, covert coping and performance-based self-esteem as well as significantly
      less winter/fall deterioration in the serum concentration of the
      regenerative/anabolic hormone dehydroepiandrosterone-sulfate. CONCLUSIONS: Our
      findings indicate a more beneficial long-term health effect of the art-based
      intervention compared to a conventional approach. Positive results for both
      standardized questionnaires and biological parameters strengthened the findings.
      The study provides a rationale for further evaluation of the effectiveness of
      this alternative educational approach.

PMID- 21196806
TI  - Patients with cluster a personality disorders in psychotherapy: an effectiveness
      study.
AB  - BACKGROUND: While psychopharmacological studies are common in patients with
      cluster A personality disorders, the effects of psychotherapy have received
      little attention. The aim of this study is to explore whether psychotherapeutic
      treatment yields health gains for these patients. METHODS: The study was
      conducted between March 2003 and June 2008 in 6 mental health care centres in the
      Netherlands, with a sample of 57 patients with a DSM-IV-TR axis II cluster A
      diagnosis. Patients were assigned to 3 settings of psychotherapeutic treatment
      (outpatient, day hospital, inpatient), and effectiveness was assessed at 18
      months after baseline. An intention-to-treat analysis was conducted for
      psychiatric symptoms (Brief Symptom Inventory), psychosocial functioning (Outcome
      Questionnaire-45) and quality of life (EQ-5D), using multilevel statistical
      modelling. As the study was non-randomised, the propensity score method was used
      to control for initial differences. RESULTS: Patients in the day hospital and
      inpatient group improved substantially in terms of psychiatric symptoms, social
      and interpersonal functioning, and quality of life. Patients in the outpatient
      group showed less improvement. Direct comparison of the improvement of
      psychiatric symptoms showed significant results in favour of day hospital (p =
      0.046) and inpatient (p = 0.01) treatment, as compared to outpatient treatment.
      However, due to substantial baseline differences, this direct comparison should
      be judged carefully. CONCLUSIONS: Cluster A psychopathology is not a
      contraindication to benefit from psychotherapy. This is especially true for more
      intensive forms like inpatient and day hospital treatment. Future research should
      focus more on psychotherapeutic treatment to gain further insight into effective
      treatment options for this patient group.

PMID- 21196807
TI  - Clinical associations of deliberate self-injury and its impact on the outcome of
      community-based and long-term inpatient treatment for personality disorder.
AB  - BACKGROUND: Deliberate self-injury (DSI) is significantly associated with
      personality disorder (PD). There are gaps in our knowledge of DSI as an indicator
      of severity of psychopathology, as moderator of outcome and with regard to its
      response to different treatment programs and settings. METHODS: We compare 2
      samples of PD with (n = 59) and without (n = 64) DSI in terms of clinical
      presentation, response to psychosocial treatment and relative outcome when
      treated with specialist long-term residential and community-based programs. We
      test the assumption that DSI is an appropriate indicator for long-term inpatient
      care by contrasting the outcomes (symptom severity and DSI recidivism) of the 2
      DSI sub-groups treated in the 2 different approaches. RESULTS: PD with DSI had
      greater severity of presentation on a number of variables (early maternal
      separation, sexual abuse, axis-I comorbidities, suicidality and inpatient
      episodes) than PD without DSI. With regard to treatment response, we found a
      significant 3-way interaction between DSI, treatment model and outcome at 24
      month follow-up. PD with DSI treated in a community-based program have
      significantly greater chances of improving on symptom severity and recidivism of
      self-injurious behaviour compared to PD with DSI treated in a long-term
      residential program. CONCLUSIONS: Although limitations in the study design invite
      caution in interpreting the results, the poor outcome of the inpatient DSI group
      suggests that explicit protocols for the management of DSI in inpatient settings
      may be beneficial and that the clinical indications for long-term inpatient
      treatment for severe and non-severe PD may require updating.

PMID- 21196808
TI  - SCL-90-R symptom profile clusters among inpatients undergoing psychodynamic group
      psychotherapy: cluster stability, associations with clinical characteristics and
      treatment outcome.
AB  - BACKGROUND/AIMS: Based on pretreatment psychopathological symptoms measured with
      the Symptom Checklist 90 Revised (SCL-90-R), this study investigated whether
      stable symptom clusters exist among psychotherapy inpatients. Furthermore, it was
      examined whether the identified clusters would differ with respect to clinical
      characteristics and treatment outcome. SAMPLING AND METHODS: We collected data
      from a total of 3,688 psychotherapeutic inpatients involved in psychodynamic
      group psychotherapy from 10 hospitals. Ipsatized SCL-90-R presymptom data were
      used as input variables for a series of cluster analyses combining hierarchical
      (Ward algorithm) and non-hierarchical (k-means) procedures. RESULTS: The cluster
      analyses revealed a 7-cluster solution with the following subgroups: (1) insecure
      paranoid, (2) neutralizing, (3) phobic-anxious, (4) aggressive, (5) insecure
      phobic, (6) somatizing, and (7) obsessive-depressive. Cross-validation with
      independent data sets, as well as alternative statistical procedures, confirmed
      the stability of the 7-cluster solution. Correlations with clinical diagnoses and
      interpersonal problems indicate the clinical relevance of the cluster
      differentiation. The cluster insecure-phobic proved to be less beneficial when
      used as a predictor of treatment outcome. Furthermore, we found moderator effects
      between cluster assignment and pretreatment interpersonal problems: the overall
      amount of interpersonal problems seemed to be detrimental to the patients from
      the clusters insecure-phobic and somatizing, whereas a relatively (ipsatized)
      heightened level of dominance was advantageous for improving psychopathological
      complaints of the patients from the cluster aggressive. CONCLUSIONS: We could
      identify typical and clinically meaningful symptom clusters for the population of
      inpatients undergoing psychodynamic group psychotherapy in Germany. This finding
      could help strengthen clinical research which is led by the assumption that it is
      relevant to characterize patients by a specific pattern of psychopathological
      symptoms rather than or in addition to one (or more) distinct diagnostic
      categories.

PMID- 21196809
TI  - Is familial obsessive-compulsive disorder different from sporadic obsessive
      compulsive disorder? A comparison of clinical characteristics, comorbidity and
      treatment response.
AB  - BACKGROUND: Familial and sporadic subtypes of obsessive-compulsive disorder (OCD)
      have been proposed, but have not been well studied. The aim of the study was to
      compare the clinical characteristics, comorbidity and treatment response of
      familial OCD with sporadic OCD. SAMPLING AND METHODS: We reviewed the clinical
      records of 84 familial OCD patients and 80 randomly selected sporadic OCD
      patients from a specialty OCD clinic in India. All the subjects had been
      evaluated using the specially devised topical OCD evaluation proforma, the Yale
      Brown Obsessive Compulsive Scale and the Clinical Global Impression scale. A
      diagnosis of OCD was made according to the DSM-IV criteria. RESULTS: Familial OCD
      was associated with earlier age at onset, a greater duration of untreated illness
      and more compulsions, particularly ordering and cognitive types. It was also
      associated with greater comorbidity, especially depression and other anxiety
      disorders, and treatment non-response. The sporadic group had more sexual
      obsessions and predominant obsession subtypes of OCD. In regression analysis,
      ordering compulsions, cognitive compulsions, absence of sexual obsessions,
      lifetime comorbidity of major depression and anxiety disorders and a greater
      duration of untreated illness predicted familial OCD. CONCLUSIONS: Our findings
      support the observation that familial OCD could be phenotypically different from
      sporadic forms of OCD and therefore a putative subtype of OCD.

PMID- 21196811
TI  - The prevalence of delusion-like beliefs relative to sociocultural beliefs in the
      general population.
AB  - BACKGROUND: Delusions are defined as false beliefs different from those that
      almost everyone else believes. The aim was to develop a new measure (the Cardiff
      Beliefs Questionnaire, CBQ) to establish the range and prevalence of delusion
      like beliefs (DLB) and compare these to other types of beliefs in the general
      population. SAMPLING AND METHODS: A total of 1,000 participants completed the
      CBQ, which uniquely assesses a broader range of currently held beliefs [delusion
      like (bizarre and non-bizarre), paranormal and religious and general
      political/social beliefs) using this large stratified sample. RESULTS: Strong
      belief in 1 or more DLB was reported by 39% of the participants (91% reporting
      'weak', 'moderate' or 'strong' belief in at least 1 DLB). Moreover, 25% endorsed
      at least 1 bizarre DLB (76% one or more at any strength). Endorsements of DLB
      were strongly correlated with paranormal and religious beliefs but not general
      political/social beliefs. CONCLUSIONS: Both bizarre and non-bizarre DLB are
      frequently found in the general population, lending support to the psychosis
      continuum account and need to revise key clinical criteria used to diagnose
      delusions. The good psychometric properties demonstrated by the CBQ indicate that
      this measure is a useful tool to investigate the wider continuum of beliefs held
      in the general population.

PMID- 21196810
TI  - Do depressed patients lose their sense of humor?
AB  - BACKGROUND: Humor is an important coping mechanism and can improve mood. However,
      it is unclear whether depressed patients are able to enjoy funny material, e.g.
      jokes, and make use of their sense of humor for coping with adverse situations.
      This study aims at investigating the influence of depression on various aspects
      of humor abilities such as sense of humor, appraisal of funny material and
      exhilaration. SAMPLING AND METHODS: Nineteen patients with major depression and
      18 healthy controls were examined with standardized self-assessment
      questionnaires to study potential group differences in humor type preferences,
      state and trait cheerfulness, seriousness and bad mood as well as humor coping.
      RESULTS: Patients and controls did not differ in their humor type preferences and
      the degree to which humorous stimuli were rated as being funny. The readiness to
      react to funny stimuli with exhilaration was significantly less pronounced in the
      patient group. The patients' tendency to use humor as a coping strategy was
      significantly lower than in the control group. CONCLUSION: The susceptibility to
      humorous material seems to be unaffected by the disorder. Introducing means to
      promote humor behavior might therefore be beneficial to depressed patients. Study
      limitations were that only self-rating instruments were used and that the
      medication was inhomogeneous.

PMID- 21196812
TI  - Cortical areas involved in numerical processing: an intraoperative
      electrostimulation study.
AB  - BACKGROUND: Numerical processing is important in our everyday lives. However,
      very few attempts have been made to map the numerical processing function areas
      during lesion surgery. OBJECTIVE: To identify and protect the cortical areas
      involved in numerical processing, the authors used the intraoperative brain
      mapping approach to study numerical processing areas in patients with parietal
      lobe tumors. METHODS: During resection in patients with parietal lobe tumors,
      local anesthesia was administered and numerical processing mapping was performed.
      Our mapping procedures were conducted before glioma removal and included
      somatosensory, language and numerical processing tasks. We focused on the
      numerical processing task. RESULTS: Different brain sites within the parietal
      lobe were detected to be specifically related to multiplication or subtraction
      processing. They displayed precise spatial distribution and overlapped with each
      other. No brain sites were found to be specifically related to numerical
      processing in the right hemisphere. CONCLUSIONS: To improve the quality of
      resection while minimizing the neurological deficits, functional boundaries of
      numerical processing areas should be considered during the removal of a parietal
      low-grade glioma. Moreover, only the left intraparietal sulcus is necessary for
      numerical processing, whereas the right intraparietal sulcus does not appear to
      be critically involved in numerical processing.

PMID- 21196813
TI  - Storage conditions of skin affect tissue structure and subsequent in vitro
      percutaneous penetration.
AB  - Storage of skin at low temperatures may affect its structure. There is no report
      in the literature on the correlation between spatially resolved skin structure
      and percutaneous penetration after different storage conditions. The present
      study applies imaging techniques (multiphoton excitation fluorescence microscopy)
      and in vitro percutaneous penetration of caffeine under four different storage
      conditions using skin samples from the same donors: fresh skin, skin kept at -20
      degrees C for 3 weeks (with or without the use of polyethylene glycol) and at -80
      degrees C. Our results show a correlation between increasing permeation of
      caffeine and tissue structural damage caused by the storage conditions, most so
      after skin storage at -80 degrees C. The presented approach, which combines
      imaging techniques with studies on percutaneous penetration, enables the link
      between tissue damage at selected depths and penetration into the upper layers of
      the epidermis to be investigated.

PMID- 21196814
TI  - Confocal Raman microspectroscopy for evaluating the stratum corneum removal by 3
      standard methods.
AB  - BACKGROUND/AIMS: Stratum corneum (SC) removal is needed in biopharmaceutical
      studies or in evaluating the barrier function. The most common technique is the
      tape stripping method. However, it results in neither a homogeneous nor a
      complete removal. METHODS: The removal qualities of tape stripping, cyanoacrylate
      skin surface biopsy and trypsinization were estimated in vitro via histological
      imaging and confocal Raman microspectroscopy (CRM) and compared. In addition, the
      potential of the noninvasive CRM as a replacement method is discussed. RESULTS:
      Comparison between the 3 methods showed, as expected, that the tape stripping
      method did not result in a uniform removal over the whole surface even after 28
      strips. The trypsinization and cyanoacrylate skin surface biopsies allowed a
      complete and uniform removal of the SC after defining a standard protocol (2
      cyanoacrylate strips with a polymerization time of 15 min). CONCLUSION: The
      feasibility of CRM to control SC removal was demonstrated in vitro. Tape
      stripping is a simple method, but it is influenced by many extrinsic factors and
      axial drug quantification is difficult. With trypsinization and cyanoacrylate
      methods, the entire SC is removed so that quantification over the whole SC is
      possible but not an axial drug screening.

PMID- 21196816
TI  - [Malaria: an update].
AB  - More than 100 years have passed since the discovery of its aetiological agent,
      but malaria is still the first cause of morbidity and mortality in the world.
      After the initial illusory successes of the fight against the infection, malarial
      infection is currently in a phase of expansion due to the sum of several
      contributory factors: the rise of anophelism related to the failure of
      eradication campaigns in endemic areas, due to environmental, structural and
      economic causes; the spread of stocks of chloroquine-resistant Plasmodium
      falciparum in such areas; the increase in travel for work and tourism, and the
      flows of populations due to wars, political issues, or just survival. In this
      paper we inspected all the aspects of the infection, from historical aspects - in
      which there was sometimes a mingling of history and legend - to those more
      properly defined as scientific. We seek to point out less well-known details,
      both about the vector and the clinical-epidemiological aspects concerning the
      populations in endemic areas, semi-immune subjects and foreigners. We also
      underline the importance both of prophylaxis and treatment of infection in
      travellers in high-risk areas, in the light of pharmacological resistance
      developed by the parasite and of the new usable molecules.

PMID- 21196815
TI  - Pancreatic adenocarcinoma up-regulated factor (PAUF) enhances the expression of
      beta-catenin, leading to a rapid proliferation of pancreatic cells.
AB  - It is not yet understood how the enhanced expression of pancreatic adenocarcinoma
      up-regulated factor (PAUF; a novel oncogene identified in our recent studies),
      contributes to the oncogenesis of pancreatic cells. We herein report that PAUF up
      regulates the expression and transcriptional activity of beta-catenin while the
      suppression of PAUF by shRNA down-regulates beta-catenin. The induction of b
      catenin by PAUF is mediated by the activities of Akt and GSK-3beta, but
      inhibition of downstream ERK does not reduce beta-catenin expression. To test
      whether PAUF emulates either the Wnt3a-mediated or the protein kinase A-mediated
      signaling pathway for the stabilization of beta-catenin, we examined the
      phosphorylation status of beta-catenin in the presence of PAUF compared with that
      of beta-catenin during treatment with Wnt3a or dibutyryl cAMP, a cell permeable
      cyclic AMP analogue. PAUF expression induces phosphorylation at Ser-33/37/Thr-41
      and Ser-675 of beta-catenin but no phosphorylation at Ser-45, indicating that a
      unique phosphorylation pattern of b-catenin is caused by PAUF. Finally, the
      expression of PAUF up-regulates both cyclin-D1 and c-Jun, target genes of beta
      catenin, leading to a rapid proliferation of pancreatic cells; conversely
      decreased PAUF expression (by shRNA) results in the reduced proliferation of
      pancreatic cells. Treatment with hexachlorophene (an inhibitor of beta-catenin)
      reduces the proliferation of pancreatic cells despite the presence of PAUF. Taken
      together, we propose that PAUF can up-regulate and stabilize beta-catenin via a
      novel pattern of phosphorylation, thereby contributing to the rapid proliferation
      of pancreatic cancer cells.

PMID- 21196817
TI  - [Hospital consumption of antibiotics at the Policlinico Hospital of the Second
      University of Naples: results of retrospective data collection].
AB  - In the therapeutic field, analysis of antibiotics consumption and use is of great
      importance: it is considered a necessary prerequisite for initiating measures to
      rationalize the use of antibiotics, but also to limit bacterial resistance. In
      this light, we conducted an observational study on antibiotics consumption at the
      Policlinico University Hospital in Naples to evaluate the prescription of
      antibiotics in the hospital's four main divisions. We used the Defined Daily Dose
      (DDD) as a measure of antibiotics consumption, and collected data retrospectively
      from 2006 to 2007. Our findings clearly show a 23.3% increase in antibiotics
      consumption in 2007 vs 2006. The classes of antibiotics experiencing the greatest
      percentage increases were penicillins and other beta-lactams, quinolones and
      glycopeptides. In particular, among other beta-lactams (J01D) in 2007 was the
      consumption of third-generation cephalosporins and carbapenems. The surgical
      division showed the largest increase in use of antibiotics, while in intensive
      care we found a reduction. Our data suggest consumption data should be compared
      with information on prescriptions and costs so as to monitor more closely the
      consumption of antibiotics and thus rationalize their use with a view to reducing
      the phenomenon of bacterial resistance. Finally, it would be useful to launch a
      training program for the proper use of antibiotics in our University Hospital.

PMID- 21196818
TI  - [In vitro synergism of ulifloxacin plus piperacillin/tazobactam against clinical
      isolates of Enterobacteriaceae producing extended-spectrum or AmpC-type beta
      lactamases].
AB  - Extended spectrum beta-lactamase (ESBL) and ampicillinase C (AmpC) producing
      Enterobacteriaceae are nowadays frequently isolated in clinical practice.
      Carbapenems are generally the drugs of choice in such a case and resistance to
      these molecules is on the rise. Rationalizing their use is to be considered
      essential, possibly identifying alternative regimens. We thus examined 10 strains
      of Enterobacteriaceae isolated from patients previously unsuccessfully treated
      with a beta-lactam or a quinolone; eight strains were either ESBL or AmpC
      producers. Ulifloxacin showed minimum inhibitory concentrations (MICs) lower than
      ciprofloxacin and levofloxacin. Tested with the checkerboard method, the
      association of ulifloxacin and piperacillin/tazobactam proved fully synergistic
      on five strains and partially synergistic on three. The above association was
      fully synergistic towards three strains resistant to piperacillin/tazobactam and
      one strain resistant to ulifloxacin, with MICs in association easily obtainable
      at standard doses. Our in vitro study demonstrates a synergistic activity of
      ulifloxacin and piperacillin/tazobactam in association towards ESBL and AmpC
      producing Enterobacteriaceae. Clinical studies are needed to confirm in vivo the
      effectiveness of this regimen.

PMID- 21196819
TI  - Cost analysis of ventilator-associated pneumonia in Turkish medical-surgical
      intensive care units.
AB  - A study was carried out to assess treatment success and the overall costs of
      patients with ventilator-associated pneumonia (VAP). In a prospective case
      control study, data were collected from 25 intensive care unit (ICU) beds. A
      total of 162 ICU patients who required mechanical ventilation were assessed. Of
      these, 81 patients were diagnosed with VAP and the other 81 were controls
      (without VAP). Risk of mortality was analyzed and total cost of care was
      recorded. Age, sex and underlying disease were similar between the groups. The
      mean length of stay (LOS) in the ICUs in the VAP cases (15.7+/-9.1 days) exceeded
      that of the controls (4.9+/-4.9 days) (p 0.0001), and the additional LOS
      attributable to VAP was estimated at 10.8 days. In the VAP group, 25 patients had
      early-onset VAP, and the other 56 patients had late-onset VAP. Mortality rates
      were higher in VAP patients (32%) than controls (19.7%) p 0.05). Total costs were
      USD 8602.7+/-5045.5 in the VAP group and USD 2621.9+/-2053.3 in controls. The
      additional cost for VAP was found to be USD 5980 per patient. These data suggest
      that morbidity, mortality, ICU length of stay and costs increase with VAP. The
      additional costs for VAP are especially based on the use of novel and expensive
      antibiotics, other drugs, and medical material.

PMID- 21196820
TI  - [Ileocaecal intussusception associated with adenovirus infection: a case report].
AB  - Intestinal intussusception is the invagination of an intestinal segment into
      another. Childhood intussusception is usually idiopathic, whereas adult
      intussusception is usually due to a definable intraluminal lesion or to a
      systemic disease. Although the aetiology of idiopathic forms often remains
      unclear, there is appreciable evidence to support an indirect role played by
      certain infectious agents. In this report we present a case of childhood
      intussusception probably due to adenovirus infection.

PMID- 21196821
TI  - [Respiratory and uro-genital infection with bacillus of Calmette-Guerin following
      administration as a local adjuvant therapy of bladder carcinoma].
AB  - An exemplary case report of dual-site, respiratory and genito-urinary
      granulomatous infection caused by bacillus of Calmette-Guerin (BCG) in a patient
      with prior pulmonary tuberculosis and with chronic obstructive pulmonary disease
      (COPD), treated for several weeks with local, intravesical adjuvant BCG therapy
      for a relapsing transitional bladder carcinoma, is presented and discussed in the
      context of the cumbersome diagnostic and differential diagnostic process, as well
      as recent findings in the literature. Only four cases of respiratory BCG-itis
      (tuberculosis-like forms) have been reported until now to the best of our
      knowledge (two of them following bladder instillation of BCG), but our case is
      the only one which showed a dual, concurrent granulomatous localization of BCG
      itis, also involving the genito-urinary tract.

PMID- 21196822
TI  - Retinopathy in chronic hepatitis C patients during interferon treatment: a case
      report.
AB  - Ocular involvement, mainly as optic neuropathy or retinopathy, in the course of
      interferon therapy is clinically rare, while the subclinical retinal toxicity is
      quite frequent. We present a case of retinal toxicity during treatment with PEG
      INF alpha 2b and ribavirin for HCV hepatitis. We suggest that all patients
      receive an ophthalmological examination at base-line and repeated
      ophthalmological examination only if clinically advisable.

PMID- 21196823
TI  - Pulmonary embolism and acute cytomegalovirus infection in an immunocompetent
      patient.
AB  - A case of an immunocompetent man with acute CMV infection associated with a
      pulmonary embolism is described. Acute CMV infection could be a risk factor for
      developing thromboembolism. Pulmonary embolism should be included in differential
      diagnosis in patients with acute CMV infections and pulmonary opacities.

PMID- 21196824
TI  - [Prolonged novel Influenza A (H1N1) in neutropenic patients receiving
      chemotherapy].

PMID- 21196825
TI  - [Garibaldi's wounds].
AB  - On the 150th anniversary of the Unification of Italy in 1860, this paper relates
      the events linked to Giuseppe Garibaldi wounding by fire-arms as well as the
      difficulties encountered while the famous patient was being treated. The class of
      physicians, widely represented among the ranks of Garibaldi volunteers,
      enthusiastically joined the Italian Risorgimento. Its contribution was essential
      to the immediate treatment of the wounded on battlefields. Garibaldi himself,
      during his military career, was struck by fire-arms on at least three occasions.
      In particular, this issue covers the diagnostic and therapeutic problems to be
      tackled following his wounding by a Bersagliere on Aspromonte in 1862 as well as
      in the course of fighting against Austrian soldiers on Mount Suello (1866) during
      the Third War of Independence.

PMID- 21196826
TI  - Association between periodontal disease and bone mineral density in
      postmenopausal women: a cross sectional study.
AB  - OBJECTIVES: Both periodontitis and osteoporosis represent major health problems
      especially in elderly women. The relationship between the two diseases and oral
      bone loss is important having significant public health impact in the prevention
      of morbidity and mortality related to these disorders. The present study was
      aimed to investigate the possible association between osteoporosis and
      periodontal disease among postmenopausal women residing in Goa, India. STUDY
      DESIGN: A complete periodontal examination (all teeth except third molar)
      including plaque index (PI), gingival index (GI), clinical attachment loss (CAL)
      measurement was performed on 80 dentate Goan postmenopausal women (age>=50 yrs)
      with generalized chronic periodontitis. Mean alveolar bone loss (ABL) was
      measured from full mouth intraoral periapical radiographs, by recording the
      distance from cementoenamel junction (CEJ) and the most coronal portion of
      alveolar crest at mesial and distal aspect of all teeth except canines and third
      molars. Systemic bone loss was determined from hand-wrist radiograph of the
      patient through Digital X-Ray Radiogrammetry. Statistical analysis was done to
      assess the relationships between periodontal variables and bone mineral density
      (BMD) after adjusting for age, years since menopause, body mass index (BMI),
      smoking, number of remaining teeth, PI and GI. RESULTS: Age of the patient, years
      since menopause and BMI showed significant correlation with BMD. CAL and ABL
      showed mildly negative and statistically non-significant correlation with the
      BMD. Of all the variables studied, only smoking and BMI were strong predictors of
      BMD. CONCLUSION: Skeletal BMD is related to interproximal ABL and CAL, though not
      to a statistically significant level; implicating postmenopausal osteopenia as a
      risk indicator for periodontal disease.

PMID- 21196827
TI  - Risk factors for oral allergy syndrome in patients with seasonal allergic
      rhinitis.
AB  - BACKGROUND: Oral allergy syndrome (OAS) is a unique allergic reaction to food,
      which is caused by cross-reactivity between proteins in fresh fruits or
      vegetables and pollens. Predisposing factors for OAS are not well known in
      patients with seasonal allergic rhinitis. OBJECTIVE: Identify the probable risk
      factors for OAS in patients with seasonal allergic rhinitis. STUDY DESIGN: One
      hundred and eleven consecutive patients with seasonal allergic rhinitis were
      included. Patients were evaluated in terms of symptom scores and skin prick test
      positivity scores. Prick-by-prick tests with the fresh fruit or vegetable were
      carried out in patients who describe oral allergy syndrome. Patients with OAS and
      without OAS were compared statistically. RESULTS: OAS was more frequent in
      females than males (p=0.01). Odds ratio for gender (male/female) was 3.80 (95%
      confidence interval: 1.28-11.32). Within nasal symptoms, only nasal itching was
      related with OAS (P<0.05). The logistic regression analysis revealed a
      significant association between the prevalence of the OAS and age, asthma, TSS
      and TSTP (p<0.05). CONCLUSION: Not all patients with seasonal allergic rhinitis
      develop OAS. It is likely that, patients with OAS have some additional risk
      factors other than atopy.

PMID- 21196828
TI  - An in vitro comparison of different adhesive strategies on the micro push-out
      bond strength of a glass fiber post.
AB  - OBJECTIVES: To evaluate in vitro the push-out bond strengths of a glass fiber
      post adhesively luted with self-etching resin based and self-adhesive luting
      cements, as well as modified application procedure of self-adhesive luting
      cements in combination with single step self-etch adhesives. MATERIALS AND
      METHODS: Fifty single-rooted human maxillary central incisor teeth were
      endodontically treated and divided into five groups (n=10). Glass fiber posts
      (RelyX Fiber Post) were cemented with the following materials: group 1: ED Primer
      II/Panavia F 2.0 (PAN); group 2: RelyX Unicem (RU); group 3: Maxcem (MC); group
      4: Adper Prompt L-Pop (PLP)/RelyX Unicem; group 5: Optibond all-in-one
      (OB)/Maxcem. Bonded specimens were cut (1-mm-thick sections) and push-out tests
      were performed (crosshead-speed, 0.5 mm/min). Data were analyzed by one-way ANOVA
      followed by the Tukey-HSD test for post hoc comparisons at a = 0.05. RESULTS: The
      highest bond strength was recorded for groups 4 and 2, with no statistically
      significant differences among them (p >0.05). Group 4 showed significantly higher
      bond strength than group 1 (p <0.001), group 3 (p <0.0001) and group 5 (p
      <0.0001). Group 1 showed significantly higher bond strength than the group 3 (p
      <0.05). No statistically significant differences were observed among group 1 and
      group 2, group 1 and group 5, group 3 and group 5. Group 3 showed significantly
      lower push-out bond strength than the all other luting strategies except for the
      group 5. CONCLUSIONS: The push-out bond strength values of modified application
      procedure of self-adhesive luting cements (RU and MC) in combination with single
      step self-etch dentin adhesives (PLP and OB) did not improve the push-out bond
      strength of fiber post when compared with those where the conventional use of
      self-adhesive cements.

PMID- 21196829
TI  - Comparative study of two local anesthetics in the surgical extraction of
      mandibular third molars: bupivacaine and articaine.
AB  - OBJECTIVE: The third molar extraction is one of the most common surgical
      procedures in oral surgery and is usually accompanied by postoperative
      discomfort. It has been suggested that the longer duration of action of
      bupivacaine associated with the residual analgesia and the gradual onset of pain,
      could decrease the need for analgesics during the postoperative period. This
      study aims to compare the efficacy and safety of bupivacaine and articaine as
      local anesthetics for the extraction of mandibular third molars and to check
      whether bupivacaine produced residual analgesia. STUDY DESIGN: We compared
      bupivacaine 0.5% and articaine 4% with an epinephrine concentration of 1:200 000
      in a crossover design model of extraction of bilaterally symmetrical mandibular
      third molars. RESULTS: Regarding efficacy, patients experienced less
      postoperative pain at 6 and 12 hours and shorter duration of soft tissue
      anesthesia with articaine. With respect to safety, no differences were found
      between the anesthetics compared, showing a similar local and systemic toxicity.
      With regard to the preference of patients, it was higher for articaine, the main
      reasons being the greater postoperative pain and swelling with bupivacaine.
      CONCLUSION: It can be concluded that articaine seems to be a more appropriate
      anesthetic for the extraction of mandibular third molars due to the shorter
      duration of the anesthetic effect in the soft tissues, lower pain reported by
      patients during the immediate postoperative period and the personal preference of
      patients for this drug.

PMID- 21196830
TI  - Neutrophils infiltration is early event of an oral mucosal xenotransplantation
      model.
AB  - INTRODUCTION: As important effector cells of the innate immune system,
      neutrophils are involved in rejection of solid organ and/or tissue transplants.
      But their role in rejection of oral mucosa transplantation (OMT) remains unclear.
      The aim of this study is to observe the spatial-temporal change of neutrophils
      during acute rejection of OMT. METHODS: In a rat model of oral mucosal
      xenotransplantation, myeloperoxidase (MPO), an indicator of influx of neutrophils
      was detected by technique of ELISA on day 7 and 30 (D7, D30) of
      posttransplantation. RESULTS: On D7, MPO level (6.183+/-0.416, x102 ng/mg) in the
      OMT group was significantly higher than in trauma (0.681+/-0.073, x102 ng/mg) and
      normal controls (0.262+/-0.043, x102 ng/mg) (P<0.001, respectively), and this
      level was found to correlate with the index of submandibular lymph nodes (ILN),
      an indicator of inflammation of rejection (r=0.909, P<0.05). Moreover, this level
      was decreased significantly under FK506 treatment (2.103+/-0.146, x102 ng/mg,
      P=0.005). On D30, MPO in the OMT group (1.063+/-0.096, x102 ng/mg) was lower
      significantly than that on D7 (P<0.001), although this level was still higher
      that of normal controls on D30 (0.532+/-0.112, x102 ng/mg, P=0.042). CONCLUSION:
      Neutrophils infiltration was an early event of OMT, which may play important
      roles on acute rejection of OMT.

PMID- 21196831
TI  - Effect of alloy type and casting technique on the fracture strength of implant
      cemented structures.
AB  - OBJECTIVES: To evaluate the influence of alloy type and casting procedure on the
      fracture strength (FS) of metallic frameworks for implant-supported fixed
      prostheses. STUDY DESIGN: Thirty three-unit structures for lower posterior
      bridges were waxed-up and randomly assigned to two groups (n=15) according to
      alloy type and casting technique: Group 1 (C): cobalt-chromium cast in a
      centrifugal machine (TS1, Degussa-Huls); Group 2 (T): titanium cast in a pressure
      differential device (Cyclarc II, Morita). Each structure was cemented onto two
      prefabricated abutments under a constant seating pressure. After 6 months of
      water aging, samples were loaded in a static universal testing machine (EFH/5/FR,
      Microtest) until fracture. Axial compressive loads were applied at the central
      fossa of the pontics. FS data were recorded and surface topography of the
      fractured connectors was SEM-analyzed. A Chi-Square test was performed to assess
      the dependence of pores on the alloy type and casting procedure. ANOVA and
      Student-Newman-Keuls (SNK) tests were run for FS comparisons (p <0.05). RESULTS:
      One third of the C structures showed pores inside the fractured connectors. T
      frameworks demonstrated higher FS than that of C specimens exhibiting pores
      (p=0.025). C samples containing no pores recorded the greatest mean FS (p
      <0.001). CONCLUSIONS: Fracture strength of metallic frameworks depended on the
      alloy type and casting procedure. Cobalt-chromium casts often registered pores
      inside the connectors, which strongly decreased the fracture resistance. An
      accurate casting of titanium with a pressure-differential system may result in
      the most predictable technique under the tested experimental conditions.

PMID- 21196832
TI  - The development and inflammatory features of radiotherapy-induced glossitis in
      rats.
AB  - OBJECTIVES: To improve the existing animal models (mice, rats, and hamsters) for
      radiotherapy-induced oral mucositis (RTOM), thereby establishing a radiotherapy
      induced glossitis (RTG) Sprague-Dawley (SD) rat model. STUDY DESIGN: A lead
      device was designed to limit radiation exposure to a 1x1 cm2 area of a rat 's
      dorsal anterior tongue with a single 30 Gy of X-ray radiation. The general
      conditions of the irradiated rats, such as body-weight and behavior, were
      observed. The oral mucositis index (OMI) of the RTG rats were measured daily.
      Histological changes of the irradiated tongue tissues were assayed by H &E
      staining. RESULTS AND CONCLUSION: No significant changes were clinically observed
      3 to 4 days after irradiation. At 5 to 6 day, punctuation and confluenced redness
      of the mucosa were observed. The small blood vessels became more extensive,
      engorged, thin vessel walls. More infiltrating cells were observable, necrosis
      and exfoliation of the squamous cells appeared, and the formation of an
      ulcerative lesion could be observed. Seven to 15 days, the exfoliated epithelial
      layer was observed to have formed an ulcerative lesion, then aggravated
      ulcerative lesions consisting of pseudomembranous filament exudates could be
      observed. The structure of the epithelium had become completely disintegrated,
      forming deep, microscopic ulcerative lesions. Twenty-one days, the periphery of
      the ulcer was observed to have begun to heal, and granulation tissue could be
      observed at the bottom of the ulceration. At 35 days after irradiation, the
      epithelial structure presented again, but the epithelium was very thin. An RTG
      animal model was successfully established in SD rats, which provides a new
      research platform for the study of RTOM pathogenesis.

PMID- 21196833
TI  - Microbial leakage of MTA, Portland cement, Sealapex and zinc oxide-eugenol as
      root-end filling materials.
AB  - OBJECTIVE: The aim of this study was to compare the microbial leakage of mineral
      trioxide aggregate (MTA), Portland cement (PC), Sealapex and zinc oxide-eugenol
      (ZOE) as root-end filling materials. STUDY DESIGN: An in vitro microbial leakage
      test (MLT) with a split chamber was used in this study. A mixture of facultative
      bacteria and one yeast (S. aureus+E. faecalis+P. aeruginosa+B. subtilis+C.
      albicans) was placed in the upper chamber and it could only reach the lower
      chamber containing Brain Heart Infusion broth by way of leakage through the root
      end filling. Microbial leakage was observed daily for 60 days. Sixty maxillary
      anterior human teeth were randomly assigned to different groups--MTA and PC (gray
      and white), Sealapex+zinc oxide and ZOE, control groups and subgroups to evaluate
      the influence of EDTA for smear layer removal. These materials were further
      evaluated by an agar diffusion test (ADT) to verify their antimicrobial efficacy.
      Data were analyzed statistically by Kruskal-Wallis and Mann-Whitney test.
      RESULTS: In the MLT, Sealapex+zinc oxide and ZOE did not show evidence of
      microbial leakage over the 60-day experimental period. The other materials showed
      leakage from the 15th day. The presence of smear layer influenced microbial
      leakage. Microbial inhibition zones were not observed in all samples tested by
      ADT. CONCLUSION: Sealapex+zinc oxide and ZOE did not show microbial leakage over
      the experimental period, whereas it was verified within 15 to 45 days in MTA and
      Portland cement.

PMID- 21196834
TI  - Soft tissue pathosis associated with asymptomatic impacted lower third molars.
AB  - OBJECTIVE: The aim of this study was to identify the prevalence of pathological
      changes in the pericoronal tissue of asymptomatic impacted lower third molars and
      to assess the correlation between pathological changes and patient demographic,
      radiographic and morphological characteristics. STUDY DESIGN: Follicles
      associated with fully impacted lower third molars were submitted for histological
      examination after surgical extraction from 50 patients. The correlation between
      pathological changes in the dental follicle and age, gender, depth of impaction,
      angular position, and coverage and tooth development was analyzed. RESULTS:
      Cystic changes were observed in 10% of specimens and inflammatory changes in 62%.
      Incidence of pathological changes was significantly higher in Class B impacted
      teeth when compared to Class C impacted teeth. A significant correlation was
      found between epithelial cell activity and the completion of tooth development.
      CONCLUSION: We recommend monitoring all third molars whether or not they are
      symptomatic and conducting histopathological analyses on all surgically extracted
      follicle tissue.

PMID- 21196835
TI  - Is supraperiosteal infiltration anesthesia safe enough to prevent inferior
      alveolar nerve during posterior mandibular implant surgery?
AB  - OBJECTIVES: There is no agreement on using inferior alveolar nerve (IAN) block or
      supraperiosteal infiltration anesthesia during dental implant surgery in the
      posterior mandibular region. The aim of this study was to evaluate the
      effectiveness of supraperiosteal infiltration anesthesia on posterior mandibular
      region during dental implant surgery. MATERIALS AND METHODS: In this study 52
      implants were inserted under supraperiosteal infiltration anesthesia in 29
      patients. After the surgery, patients were instructed to note their pain and/or
      painless dyscomfort on the visual analogue scale (VAS). Their pressure pain
      threshold (PPT) scores were evaluated by mechanical algometer. The distance
      between the apical end of the implants and IAN was measured by using calipers on
      postoperatif panoramic radiographs. RESULTS: 50 implants to 27 patients had been
      able to place without pain under supraperiosteal infiltration. Implants which
      were placed at the mandibular second premolar and first molar region had been
      able to place with free of pain with supraperiosteal infiltration. There was no
      relationship among the distance between the apical ends of the implants and IAN
      with intraoperative discomfort of the patients. VAS scores during implant
      placement at the second premolar region were relatively higher than at the first
      and second molar region. CONCLUSION: Supraperiosteal infiltration anesthesia is a
      safe and effective method for posterior mandibular implant surgery. However the
      length of the implant should be determined carefully to avoid possible damage to
      IAN during implant placement under supraperiosteal infiltration anesthesia.

PMID- 21196836
TI  - Manual toothbrushing reinforced with audiovisual instruction versus powered
      toothbrushing among institutionalized mentally challenged subjects--a randomized
      cross-over clinical trial.
AB  - AIM: To assess and compare the effectiveness of Manual toothbrushing reinforced
      with audiovisual instructions with powered toothbrushing, among the
      institutionalized mentally challenged individuals under supervision of trained
      caretakers. MATERIALS AND METHODS: A randomized cross over clinical trial of 6
      months duration which included 16 subjects consisting of two phases of three
      months, for each of the 2 groups. In group A subjects were given manual
      toothbrushes with audio-visual aid followed by the powered toothbrushes & vice
      versa for group B. All subjects were instructed by trained care takers. An
      evaluation of the plaque & gingival scores was done at the end of 1, 2 & 3 months
      for both the groups. RESULTS: Phase I showed statistically significant decrease
      in mean plaque scores (p=0.037) but insignificant mean gingival scores (p=0.189)
      in group A at end of 3 months. In phase II, statistically insignificant decrease
      in mean plaque & gingival scores were recorded at end of 3 months. In group B a
      statistically significant decrease in both plaque (p=0.002) & gingival (p=0.001)
      was found at end in both phases. Comparison of mean plaque & gingival scores of
      manual & powered toothbrushes at different intervals in both groups were
      statistically insignificant. CONCLUSION: For mentally challenged individuals,
      manual toothbrushes reinforced with audio-visual instructions for brushing may be
      comparable to the use of powered toothbrushes.

PMID- 21196837
TI  - Long-term analysis of upper incisor crowding. A longitudinal study
      orthodontically treated patients.
AB  - INTRODUCTION: Although there are numerous studies in the literature on alignment
      stability in the lower arch, there are few referring to the upper arch. AIMS: To
      assess upper arch stability (irregularity index, widths and length of arch,
      overjet and overbite) in orthodontically treated patients by comparing late
      incisor stability with the initial malocclusion and type pf treatment undertaken.
      STUDY DESIGN: The study models of 51 patients, treated with or without
      extractions, were analysed at three different points in time: pre-treatment (T1),
      post-treatment (T2) and post-retention (T3) (average 5 years). The following
      parameters were measured: irregularity index, arch length, inter-canine and inter
      molar widths, overjet and overbite. RESULTS: The results showed that upper
      incisor crowding relapses, although a net improvement is noted in comparison to
      the initial state both in cases treated with or without extractions. The arch
      length also relapses in both cases. The inter-canine and inter-molar widths as
      well as the overjet and overbite are stable in the long term. The long-term
      response of maxillary incisor alignment is unpredictable. CONCLUSIONS: There is a
      statistically significant reduction in incisor irregularity, length and width of
      arch (inter-canine and inter-molar widths), whereas overjet and overbite undergo
      a reduction of little magnitude. No statistically significant correlation is
      noted between late incisor stability and the initial malocclusion or type of
      treatment.

PMID- 21196838
TI  - Ultra-structure characterization of self-etching treated cementum surfaces.
AB  - OBJECTIVES: to evaluate the effect of different conditioning treatments on
      surface roughness and topography of dental cementum. STUDY DESIGN: Extracted
      human canines were used for the present study. The mesial surface from the
      cervical third of the roots were ground flat with wet 600-grit silicon carbide
      paper. They were polished (up to 1/4 um diamond paste) and treated as follows: 1)
      No treatment, 2) 35% H3PO4 during 15 s, 3) Clearfil SE Bond primer (SEB), 4) One
      Up Bond F (OUB). The adhesive systems were applied following manufacturer 's
      instructions. SEB primer and OUB were removed from surfaces by washing and
      ultrasonic agitation with ascending ethanol solutions. Digital images of treated
      surfaces (5x5 and 15x15 um) were obtained by means of an atomic force microscope
      (AFM) analysis. The average surface roughness (Ra nanometers) of the scanned
      areas was assessed. Data were analyzed by ANOVA and SNK multiple comparisons
      tests (p <0.05). RESULTS: phosphoric acid treatment produced the highest mean
      roughness value, at all scan sizes. At 5x5 um AFM images, for self-etch adhesive
      systems no differences in roughness were detected. At 15x15 um, when One-Up Bond
      F was employed the lowest value was obtained. CONCLUSIONS: When phosphoric acid
      treatment was applied, cementum surface roughness increased and a strong
      demineralization with exposed collagen fibers could be observed.

PMID- 21196839
TI  - Sleep bruxism. Conceptual review and update.
AB  - Sleep bruxism (SB) is a parafunctional oromotor habit that can sometimes pose a
      threat to the integrity of the structures of the masticatory system if the
      magnitude and direction of the forces exerted exceed the system 's adaptive
      capacity. Over the years science has tried to provide a consistent explanation of
      the etiopathogenesis and physiopathology of SB, although the pathophysiological
      mechanisms are even now not yet fully understood. There is at present no
      specific, effective treatment to eliminate the habit of bruxism permanently.
      There are only palliative therapeutic alternatives steered at preventing the
      pathological effects of SB on the stomatognathic system and alleviating the
      negative clinical consequences of the habit. The objective of this article is to
      review and update the fundamental scientific concepts of SB and to furnish an
      approach to the main types of therapy used, based on the scientific literature.

PMID- 21196840
TI  - Stabilization of autotransplanted teeth using thermoplastic retainers.
AB  - OBJECTIVE: Different fixation techniques have been used for stabilization of
      autotransplanted teeth. Because rigid or extended fixation periods can cause
      complications such as ankylosis and disturbances of pulpal revascularization, our
      aim was to evaluate an alternative technique, a removable splint, for improving
      the success rate of autotransplanted molar teeth. STUDY DESIGN: In 44 patients,
      (20 male and 24 female patients), 45 transplanted teeth were analyzed. These
      cases were followed for 31 to 47 months after operation. Transplanted teeth were
      evaluated after use of a thermoplastic retainer for 1 month, in terms of success
      rate and dissatisfaction with this apparatus. The primary stability, ankylosis,
      and root resorption were also analyzed. RESULTS: To date, 1 transplant was
      extracted after 6 months due to unpreventable periapical root inflammation, and 2
      transplants were extracted after one year due to external root resorption.
      Although 2 ankylosed transplants were still functional after an average follow-up
      period of three years, with no dissatisfaction by the patients, these cases were
      treated as failures because of the probable risk for external root resorption.
      The remaining 40 (88.8 % success rate) transplants remained asymptomatic and
      functioning for a mean follow-up period of 37 months. In the assessment of
      dissatisfaction with the thermoplastic retainer, 36 (81.8 %) patients had no or
      little dissatisfaction, 4 (9 %) patients had very appreciable or excessive
      dissatisfaction, and 4 (9 %) patients had moderate dissatisfaction. CONCLUSIONS:
      A thermoplastic retainer for use after autotransplantation of third molar teeth
      is a reasonable and useful method and a good alternative to conventional rigid or
      semi-rigid splints. This technique was especially useful in autotransplanted
      teeth that had poor stability, i.e., in cases in which it is conventionally
      advised to use long-term rigid or semi-rigid splints.

PMID- 21196841
TI  - Tongue lesions in a Jordanian population. Prevalence, symptoms, subject's
      knowledge and treatment provided.
AB  - Tongue lesions constitute a considerable proportion of oral mucosal lesions, and
      are health concern to both oral health care providers and public. OBJECTIVES: The
      aim of this study was to determine the prevalence of tongue lesions and
      conditions among a group of Jordanian population attending dental clinics, in
      addition to assessment of their symptoms, knowledge, and treatment provided for
      their tongue lesions. STUDY DESIGN: A total of 2000 dental out-patients were
      screened for tongue lesions. RESULTS: Fissured tongue was the most common tongue
      lesion diagnosed in 11.5% of the subjects, followed by coated tongue (8.2%),
      geographic tongue (4.8%), hairy tongue (2.4%) and median rhomboid glossitis
      (0.5%). Symptoms were reported by 28% of the subjects with geographic tongue and
      23% with fissured tongue. The majority of the subjects (ranging from 61.1%-86.4%)
      were neither aware about their tongue lesions nor worried about their prognosis.
      Less than 50% of those who were aware of their tongue lesions sought medical
      advice. CONCLUSION: The high prevalence of tongue lesions necessitates higher
      awareness of the general dental practitioner by their etiology, diagnosis and
      management.

PMID- 21196842
TI  - The mandibular angle in osteoporotic men.
AB  - OBJECTIVES: Osteoporosis induces the reduction of bone mass and screening for low
      bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) has been the
      current gold standard test to determine osteoporosis. Panoramic radiography is
      widely used in dentistry for routine examination of jaws. The objective of this
      study was to determine the relationship between the mandibular angle (MA) values
      and the vertebral bone mineral density (v-BMD) in 20 osteoporotic men. STUDY
      DESIGN: In panoramic radiograms of osteoporotic men, the means were calculated
      for the mandibular angle values measured in the right and left mandible. v-BMD
      values were also calculated by manual analysis of DXA scans. The correlation
      between these variables was assessed. RESULTS: A negatively significant
      correlation was found between the MA and v-BMD. CONCLUSIONS: The size of the
      mandibular angle decreases when osteoporosis increases. It is suggested that the
      mandibular angle may be useful in clinical dental practice to identify
      osteoporotic men with previously undetected low bone mineral density.

PMID- 21196843
TI  - Analysis of a possible association between oral lichen planus and drug intake. A
      controlled study.
AB  - OBJECTIVES: To investigate whether daily systemic and/or topical medication
      contributes to the development of oral lichen planus (OLP) lesions. STUDY DESIGN:
      The study involved 110 OLP patients and 76 control subjects, matched by age, race
      and sex. The analyzed data included medical records, drug intake and topical
      medication. Criteria for analysis of drug intake included: (1) ATC-code drug
      classification; (2) number of different drugs used daily in the categories of
      monopharmacy (1 drug), minor polypharmacy (2-4 drugs), and major polypharmacy ( >
      5 drugs); and (3) drugs implicated in lichenoid reactions (DILRs). RESULTS: Sixty
      (54.5%) of the 110 OLP patients reported daily medication (prior to the
      appearance of the OLP lesion) compared to 52 (68.4%) of the 76 control subjects.
      No statistical difference was found between the two groups in terms of systemic
      diseases, number of medicated individuals in the categories of mono- and
      polypharmacy, nor use of DILRs (P > 0.05). Regarding the clinical forms and site
      of involvement, a statistically significant difference was only found for the
      clinical erosive form of OLP, seen more frequently in non-DILR (P = 0.04) and
      nonmedicated OLP patients (P = 0.02) than in DILR OLP patients. Daily use of
      topical oral medication was reported by 2 (1.8%) OLP patients and 1 (1.3%)
      control subject. CONCLUSIONS: It seems that the use of systemic medication does
      not lead to a significant increase in the incidence of OLP lesions. For their
      part, lichenoid drug reactions are likely to occur only in a very low percentage
      of patients.

PMID- 21196844
TI  - Retrospective analysis of impacted first and second permanent molars in the
      Turkish population: a multicenter study.
AB  - OBJECTIVES: The purpose of the present study was to retrospectively analyze 170
      case series of patients with 200 impacted first and second permanent molars.
      STUDY DESIGN: Records of 104.408 patients were retrospectively screened in this
      multicenter study. The chosen study population consists of 170 patients who
      presented with impacted or retained first and second permanent molar. All
      patients with impacted first or second permanent molar had undergone clinical and
      radiographic examinations. The following factors were analyzed: age and gender,
      frequency, distribution, location, position, the number of impacted tooth,
      primary and secondary retention, degree of infraocclusion, associated pathologic
      conditions and treatment method. RESULTS: There were a total of 170 patients
      (male: 91, female: 79, mean ages 22.69 +/- 8.99 years ranging from 13 to 66 years
      of age) with 200 retained or impacted permanent molars in 104.408 patients. In
      this study, 200 impacted teeth which were analyzed were 125 molars (62.5%)
      vertical position, 17 (8.5%) horizontal, 38 (19%) mesioangular, 12 (6%)
      distoangular, and 7 (3.5%) buccolingual inclination There were 52 primarily
      retained (26%) and 32 secondarily retained (16%) molars. 137 (68.5%) molars were
      asymptomatic. Cystic formation was present in 13 (6.5%) cases. CONCLUSIONS:
      Although the impactions of first and second permanent molars do not occur
      frequently, it is important to make an early diagnosis in order to start
      treatment at the optimal time.

PMID- 21196845
TI  - Tooth size changes with age in a Spanish population: percentile tables.
AB  - OBJECTIVES: The aims of this work were: firstly, to draw up tables of percentile
      tooth sizes similar to those of Sanin and Savara for three age groups of a
      Spanish population; secondly, to describe changes in tooth size between those
      groups over time, as well as observing any sexual dimorphism and, finally, to
      compare both the Spanish and Sanin and Savara 's American population samples.
      MATERIAL AND METHODS: The sample included 359 patients and was divided into three
      age groups: adolescents, young adults and adults, of both genders. After dental
      cast digitalization, mesiodistal tooth-size was measured on each dental cast
      using a digital method. Dental size tables organized by percentiles for each
      group of age and gender were drawn up. Percentiles under 30 were considered as
      small, between 30 and 70 as average, and above 70 as large. As symmetry was found
      between contralateral teeth, the mean between the teeth of the two semi-arches
      was considered. RESULTS: The mesiodistal tooth sizes of adolescents did not
      present statistically significant differences between genders, in contrast to the
      two other age groups. CONCLUSIONS: Mesiodistal tooth diameters tended to diminish
      with age, especially in women, in the Spanish population. The values obtained for
      our dental tables, organized by percentiles, were slightly higher than those
      found by Sanin and Savara in an American population, especially for women.

PMID- 21196846
TI  - Patient safety in dentistry: dental care risk management plan.
AB  - OBJECTIVES: Although the safety of patients has been one of the inherent concerns
      of dental practice, but because the proposals made in the field of dentistry are
      few and improperly structured, this paper constitutes an attempt to present a
      proposal titled "Plan for Dental Health Care Risk Management, " promoted by the
      General Council of Dentists of Spain, including a description of the proposed
      work methodology. DESIGN: The "risk management plan " proposed in this paper is
      based on applying the basic concepts dealt with in patient safety to the field of
      dentistry, due to the fact that the available bibliography contains no specific
      "health care risk management plan " for dentistry specifically. RESULTS AND
      CONCLUSIONS: In order to implement health care risk management in the field of
      dental care provided at any level throughout Spain, a seven-step plan which
      covers the main objectives in Patient Safety is provided.

PMID- 21196847
TI  - Quantification of growth factors by using a new system for obtaining platelet
      rich plasma.
AB  - OBJECTIVE: To verify the performance of a new method for obtaining platelet-rich
      plasma, while avoiding contamination of the sample during its processing. STUDY
      DESIGN: Twenty healthy patients were selected, from whom 21 ml of blood was
      extracted. We then proceeded to study the platelets and growth factors in basal
      blood after centrifuging the sample by using a new closed system for obtaining
      platelet-rich plasma (PRP). RESULTS: After centrifuging the blood sample, double
      the amount of platelets as that found in basal blood was obtained. Of the four
      growth factors analyzed, only the factor similar to insulin (IGF) contained the
      same concentration after the centrifuge process. The platelet-derived growth
      factor (PDGF) and the vascular growth factor (VGF) were multiplied by six with
      respect to the basal values and disproportionately increased the levels of the
      transforming growth factor beta (TGF-beta). CONCLUSIONS: The new closed method
      for obtaining PRP, after avoiding contamination of the sample following its use,
      offers levels of platelet concentrate and growth factors necessary for
      regeneration.

PMID- 21196848
TI  - Evaluation of serum copper and iron levels among oral submucous fibrosis
      patients.
AB  - OBJECTIVE: To estimate and compare the levels of serum copper and iron among
      subjects with oral submucous fibrosis (OSMF) of different clinical stages and
      healthy controls. STUDY DESIGN: Study sample comprised of 50 patients clinically
      diagnosed with OSMF and 50 healthy controls who were matched for age and gender.
      OSMF patients were categorised by clinical staging. Serum estimation of copper
      and iron was done using atomic absorbtion spectrophotometry. RESULTS: Mean copper
      and iron level differed significantly (p < 0.000) between the patients and
      controls with patients exhibiting higher copper (134.1 +/- 20.16) and lower iron
      (114.78 +/- 23.47) levels in contrast to controls who presented lower copper
      (114.8 +/- 12.36) and higher iron (130.86 +/- 31.01) levels in serum. There was a
      definite trend as (P < 0.0001) with cases having the lesion in faucial bands (1st
      stage) exhibiting the lowest serum copper and those in stage 3 (faucial, labial
      and buccal bands) presenting the highest copper levels in serum. CONCLUSIONS:
      Copper level increased and iron level decreased in study group in comparison to
      healthy controls. Copper level increased as clinical stage of oral submucous
      fibrosis increased.

PMID- 21196850
TI  - Analysis of different type of transmigrant mandibular teeth.
AB  - OBJECTIVE: Until recently, most reports about transmigration have documented that
      the canine is the only tooth which can migrate to the opposite side of the arch.
      The goal of the study was to define the transmigration of different types of
      teeth in people in various regions of Turkey. STUDY DESIGN: A total of 112,873
      panoramic radiographic files from seven different Turkish cities were inspected.
      The following data were evaluated according to age, gender, number of
      transmigrant teeth, localization, eruption status, side, unilaterally or
      bilaterally and associated pathology or dental abnormalities. RESULTS: Of the
      112,873 radiographs included in the study, 90 were seen to present as
      transmigrant in 87 patients, representing 0.079% of the sample. There were only
      two (0.0017%) transmigrant lateral (TML) teeth and only three (0.0026%)
      transmigrant premolar (TMP) teeth encountered. The mean age at the time that the
      transmigrant mandibular teeth were identified was 29.9 years, with a range from
      10 to 66 years. Out of the 87 cases, 51 were female and 36 were male, with a
      male:female ratio of 1:1.41. Transmigrants were more commonly seen unilaterally
      (96.5%). The most frequent associated pathology was odontoma. CONCLUSIONS:
      Because early detection is vital to prevent complications and ensure more
      successful treatment, these extensive studies are crucial. In this extensive
      study, we indicated cases of transmigration of premolar and lateral teeth as a
      variant. Demographic variables and properties of all transmigrants (TM) were also
      presented.

PMID- 21196849
TI  - Denture-related oral mucosal lesions among farmers in a semi-arid Northeastern
      Region of Brazil.
AB  - OBJECTIVES: The purpose of this study was to evaluate the prevalence of denture
      related oral mucosal lesions (DML) in Sao Francisco sertao microregion, in
      Sergipe State, Northeastern Brazil. STUDY DESIGN: Data related to gender, age,
      type of denture, length of denture use, hygiene care, nocturnal denture wear,
      symptoms, and presence of DML were obtained. Statistical analysis included the
      Pearson 's chi-square and multivariate logistic regression. RESULTS: The global
      prevalence of DML was 50%, with a significant association between the DML and
      female gender, age >= 40 years, and length of use >= 5 years. By using the
      interaction model of logistic regression it was observed that females over 40
      years have 4.5 greater odds of developing DML compared to males of the same age
      group. The DML more common was the type 2 denture stomatitis, followed by type 1
      denture stomatitis and inflammatory fibrous hyperplasia. CONCLUSIONS: This study
      shows that the DML are more common in female over 40 years of age, suggesting
      that hormonal chances and age-related factors may favor the development of
      lesions. In addition, there is a significant association between length of
      denture use and prevalence of DML.

PMID- 21196851
TI  - Retrospective study of maxilla growth in a Spanish population sample.
AB  - This study has been designed to evaluate the vertical and sagittal changes in the
      maxilla due to growth. A sample group was chosen of 38 individuals with normal
      occlusion, composed of 16 females and 22 males between the ages of 8 and 18. The
      total sample was divided into three groups: prepubescent (8-11 years), pubescent
      (12-14 years) and post-pubescent (15-18 years). A series of cephalometric angle
      parameters (SNA, maxillary height, slope of the palatal plane and maxillary
      depth) and lineal parameters (effective maxillary length, palatal plane length,
      middle third of the face height and convexity) were traced. Superimpositions of
      the initial and final cephalometries in the Ba-N plane and in the Nasion fixed
      point were carried out to measure growth. An analytic statistical analysis was
      applied using a Student t test for independent samples in order to evaluate the
      differences found according to sex. An analysis of variance followed by Duncan's
      multiple range test was done to study the evolution of each variable throughout
      the duration of the experiment. In light of the results obtained, we have come to
      the following conclusions: sagittal growth of the maxilla is constant from the
      age of 8 to 18 years with an average increase of 0.2 mm/year. Vertical growth, as
      well as general maxillary growth, is greater in the prepubescent group.

PMID- 21196852
TI  - The status of dental caries and related factors in a sample of Iranian
      adolescents.
AB  - OBJECTIVE: To describe the status of dental caries in a sample of Iranian
      adolescents aged 14 to 18 years in Qazvin, and to identify caries-related factors
      affecting this group. STUDY DESIGN: Qazvin was divided into three zones according
      to socio-economic status. The sampling procedure used was a stratified cluster
      sampling technique; incorporating 3 stratified zones, for each of which a cluster
      of school children were recruited from randomly selected high schools. The
      adolescents agreed to participate in the study and to complete a questionnaire.
      Dental caries status was assessed in terms of decayed teeth (DT), filled teeth
      (FT) and decayed, missing and filled teeth (DMFT). A multivariate regression
      analysis was used to determine statistically significant associations between
      DMFT and other variables. RESULTS: The study sample comprised 380 adolescents,
      188 (49.5%) being male. The mean age of the adolescents was 15.42 (SD= 1.1)
      years, and the mean DMFT was 2.61 (SD=1.89). Boys had significantly higher DMFT
      scores than girls (P <0.05). The multivariate regression analyses revealed a
      significant relation between high DMFT scores and such variables as increasing
      age, male gender, lower levels of parental education, higher family income, lower
      frequency of tooth brushing and dental flossing, having a history of no visits to
      the dentist, and bad perception of own oral health. CONCLUSIONS: The present
      study reveals that Iranian adolescents have a poor oral hygiene, as very few
      subjects brush and floss their teeth on a regular basis. Although the incidence
      of caries was found to be moderate, it was influenced by demographic factors such
      as age and gender in addition to socio-behavioral variables such as family
      income, the level of education attained by parents, the frequency of dental
      brushing and flossing, and both the frequency and type of visit to a dentist.

PMID- 21196853
TI  - Evaluation of surgical-orthodontic treatments on  impacted mandibular canines.
AB  - OBJECTIVE: The aim of the study was to evaluate patients treated for impacted
      mandibular canines through a combined surgical and orthodontic approach. STUDY
      DESIGN: The cases which were made button operations of impacted mandibular
      canines were selected from 5100 panoramic radiographs taken from patients who
      made use of our oral and maxillofacial surgery services between January 1998 to
      April 2006. All of these selected patients were assessed radiographically.
      Pertinent information such as sex, age at the time of surgery, site of the
      unerupted tooth, space availability and any other associated pathoses were also
      recorded. These patients were called again, and the condition of the mandibular
      canines was evaluated with panoramic radiographs. If the tooth erupted in the
      right position and it was functional and asymptomatic, we assumed the treatment
      to be successful clinically. RESULTS: In the present study, from 5100 patients,
      69 patients had impacted mandibular canines and only 21 patients ' teeth (a total
      of 23 teeth) were treated orthodontically. Sixteen impacted mandibular canine
      teeth of 14 patients erupted successfully. Two impacted canine were extracted,
      and only one canine tooth was transplanted to the normal position. Four patients
      ended the treatment because of failure of eruption. CONCLUSION: If a mandibular
      canine tooth is impacted, not only is surgical exposure sufficient but also
      traction force must be applied orthodontically after the surgical exposure. In
      addition, age influences the success of the treatment on impacted mandibular
      canine teeth more than the position and impaction level of the teeth.

PMID- 21196854
TI  - Merkel cell carcinoma: our experience in this rare pathology.
AB  - Merkel cell carcinoma (MCC) was first described in 1972 by Toker, who described
      five cases of the so-called "trabecular carcinoma of the skin ". MCC is a rare,
      aggressive skin cancer that affects mainly the elderly. Sun exposed areas are
      mainly affected, specially the head and neck. Immunohistochemical analysis is
      essential to reach a correct diagnosis. According to the origin of MCC, the tumor
      expresses both epithelial and neuroendocrine markers. MCC has a propensity for
      recurrence, regional and distant metastases. Several treatment options are
      available, such as surgical excision or Moh's surgery, accompanied by neck
      dissection or radio and chemotherapy in advanced cases. The present study aims to
      evaluate the clinical behaviour and the evolution of five cases of this disease
      that were treated at our institution (reference to 1100000 inhabitants) in the
      last five years. It is stressed on the bad prognosis of this pathology, which
      presents high rates of locoregional recurrence, even though the recent advances
      in radio and chemotherapy.

PMID- 21196855
TI  - The influence of platform switching in dental implants. A literature review.
AB  - INTRODUCTION: The platform switching concept involves the reduction of the
      restoration abutment diameter with respect to the diameter of the dental implant.
      In 1991, dental implants of 5 and 6 mm diameter platforms were introduced.
      However, matching-diameter prosthetic abutments were not available. These
      implants were restored with "standard"-diameter prosthetic components (4.1 mm).
      Long-term follow up around these wide-platforms showed higher levels of bone
      preservation. In time, it has been called platform switching. The first case
      report applying this concept was indexed in MedLine in 2005. MATERIALS AND
      METHODS: The aim of this article is to carry out a literature review of articles
      which deal with the influence of this modified platform in hard and soft oral
      tissues. All papers involving "platform switching" that are indexed in MedLine
      and published in English were used. Clinical cases, experimental and non
      experimental studies were included, as well as literature reviews. RESULTS: In
      our search, we found: 16 clinical series or single clinical cases, 10 test and
      control studies, 9 experimental studies and 3 reviews. CONCLUSION: All papers
      written by different researchers show an improvement in perimplant bone
      preservation. Further long-term studies are necessary to confirm these results.
      The articles consulted refer to the biomechanical behavior of the abutment
      implant complex in response to occlusal loading, the maintenance of crestal bone
      height and the peculiar repositioning of the biological space.

PMID- 21196856
TI  - Immediate temporary restoration of single-tooth implants: Prospective clinical
      study.
AB  - PURPOSE: The goal of this study is to assess the survival, marginal bone loss and
      complications around single-tooth implants on which immediate provisionalization
      was carried out. PATIENTS AND METHODS: 78 implants were placed in 57 patients: 56
      after extraction and 22 in healed sockets. Immediately after surgery provisional
      crows were delivered without contacts in both centric and excursive jaw
      movements. The final crowns were inserted between 3 to 6 months later. During the
      study there were 3 x-rays taken per patient. The marginal bone loss was measured
      and complications were recorded. The statistical analysis of the data was carried
      out with the STATA 10(r) software. RESULTS: The mean duration of the study was 92
      weeks. Survival rate was 98.7% (1 failure out of 78 implants). The mean mesial
      bone loss was 0.2 +/- 0.4 mm and the mean distal bone loss was 0.2 +/- 0.4 mm. No
      statistically significant differences were found between immediate or delayed
      implants. 67 implants showed a bone loss less than 1 mm, and 36 did not show any
      bone loss at all. The main complications were the uncementing of the crowns (11
      crowns), the presence of cement remnants (10 crowns) and the development of
      apical lesions around implants (6 implants). CONCLUSION: With the limitations of
      this study, it can be concluded by saying that immediate restoration with single
      tooth implants and provisional crowns may be considered as a predictable
      technique.

PMID- 21196857
TI  - Extractions without eliminating anticoagulant treatment: a literature review.
AB  - OBJECTIVES: To establish whether there is a high enough risk of bleeding in
      patients who take oral anticoagulants, such that it would justify not using oral
      anticoagulants when performing a dental extraction, as well as if the reason for
      and anatomical location of the extraction increases such risk. STUDY DESIGN: We
      performed a bibliographic search in order to carry out a meta-analytic study
      using descriptive statistics. RESULTS: We compiled a sample of 1194 patients from
      the articles selected. Of these patients, a total of 2392 simple, serial surgical
      extractions were performed; none of the patients interrupted their anticoagulant
      treatment with warfarin sodium. Of the sample, 83 patients presented a certain
      degree of bleeding; in 77 of such cases, the bleeding was controlled with local
      hemostasis, whereas 6 patients required their dose of oral anticoagulants to be
      adjusted. There was a higher incidence of bleeding in patients presenting a
      periodontal pathology, compared to deep caries and pericoronitis. CONCLUSIONS:
      Patients being treated with oral anticoagulants represent a risk that we should
      be aware of, but local hemostasis has proven to be effective when performing
      extractions, provided that the INR value is less than 4. There is an increased
      incidence of bleeding in patients with periodontal problems, due to the greater
      presence of inflammation in the soft tissues. If the extraction is performed in
      the maxilla, the incidence of hemorrhagic complications is slightly higher than
      in the mandible, although this difference is considered to be insignificant.

PMID- 21196858
TI  - Influence of lifestyle on oral health behavior among rural residents of Udaipur
      district, India.
AB  - OBJECTIVES: To determine the relation of life style with dental health behavior
      such as tooth brushing frequency, use of extra cleansing devices and regular
      visits to dentist among rural residents of Udaipur district, India. STUDY DESIGN:
      The study population comprised of 1001 rural population between the ages 18 to 69
      years selected by multi stage stratified cluster sampling procedure. Personal
      interviews were conducted by three trained interviewers who collected information
      on socio-demographic and lifestyle factors in addition to some aspects of dental
      health behavior including tooth brushing frequency, use of extra cleaning devices
      like dental floss and regular visits to dentist. RESULTS: Majority of the
      population (63.3%) brushed their teeth once a day and only a few subjects (19.8%)
      brushed twice a day whereas 8.6 % never brushed their teeth. Logistic regression
      analysis revealed that females were more apt in every aspect of dental health
      behavior. House wives were more regular in brushing their teeth (OR=1.51) and
      using extra cleansing devices as compared to other occupation groups. Subjects
      who suffered from systemic disease showed negative association with use of extra
      cleansing devices but showed positive association with regular visits to dentist.
      CONCLUSIONS: The results indicate that dental health behavior is related with
      life style factors as well as socio-demographic variables.

PMID- 21196859
TI  - Dental arch changes from adolescence to adulthood in a Spanish population: a
      cross-sectional study.
AB  - OBJECTIVES: Given the controversy in the literature about the variations in
      intercanine and intermolar distances and arch perimeter once the eruption of
      permanent teeth is completed, the aims of this study were to assess the changes
      of these measures with age, analyzing its sexual dimorphism and variability in a
      Spanish population. STUDY DESIGN: 188 Spanish individuals distributed in three
      age groups were selected: 63 adolescents (mean age: 14.15 years), 62 young adults
      (mean age: 21.9 years) and 63 adults (mean age: 40 years). The intercanine and
      intermolar distances and arch perimeter were measured in each dental cast from
      each individual of the sample using a digital method. The results were compared
      between sex and age groups, the sexual dimorphism percentage (%) of each measure
      and its variability coefficient (VC%) were calculated. RESULTS: The results
      depend on sex and age and, therefore, these two factors will be analyzed jointly
      for each of them with the variation coefficient of the measurement. Intercanine
      and intermolar distances and arch perimeter were greater in men than in women,
      especially in the young adult and adult groups. CONCLUSIONS: The intercanine
      distance and arch perimeter tended to decrease with age particularly in the
      female sex, whilst the intermolar distance didn 't undergo significant changes.
      The intercanine distance is the dimension that presented the greatest
      variability, whereas the intermolar distance presented the least. The changes
      occur in the transition from adolescence (14 years of age) to adulthood (22 years
      of age) and the subsequent alterations are not relevant.

PMID- 21196860
TI  - The correlation between the severity of radiotherapy-induced glossitis and
      endothelial cell injury in local tissues in a rat model.
AB  - OBJECTIVES: To explore the correlation between the severity of radiotherapy
      induced glossitis (RTG) and endothelial cell injury in local tissues in a rat
      model. STUDY DESIGN: The RTG animal model was designed and used by our team. The
      Oral mucositis index(OMI) was documented daily. Immunohistochemistry (IHC)
      Staining of CD34 was utilized to identify endothelial cells in the RTG tissues.
      Apoptosis of endothelial cells in local lesions due to RTG was detected by the
      TUNEL assay. The dynamic relationship between the OMI and apoptotic endothelial
      cells was statistically analyzed by time. RESULTS AND CONCLUSIONS: The injury and
      apoptosis of endothelial cells were observed 3 day post-irradiation. The vascular
      lumens of the post-irradiation tongue lesions were irregular; thrombosis
      formation in the center of the lumens, unsmooth lumen walls and vasodilated
      vessels were observed. Also, endothelial cells detached from the basal membrane
      and were found in the lumens. The percentages (%) of apoptotic endothelial cells
      were 78.3 +/- 0.31 (5 day); 89.3 +/- 0.83 (8 day); 83.5 +/- 0.41 (14 day); 69.3
      +/- 0.57 (21 day); and 47.3 +/- 0.59 (28 day). The OMI was correlated with the
      percentage of apoptotic endothelial cells (R=0.67, P=0.034). Summary, endothelial
      cell injury was correlated with the pathogenic condition of RTG.

PMID- 21196861
TI  - Dental implants in patients with oral mucosal alterations: An update.
AB  - OBJECTIVE: To determine whether a series of diseases of the oral mucosa - Sjogren
      syndrome, ectodermal dysplasia, epidermolysis bullosa and lichen planus - reduce
      the survival rate of dental implants. MATERIAL AND METHOD: A Medline search was
      carried out using the key words: " Sjogren syndrome ", "ectodermal dysplasia ",
      "epidermolysis bullosa ", "lichen planus " and "dental implants ", including
      those publications involving clinical series comprising more than one patient
      with the mentioned disorders and treated with dental implants, in the last 10
      years. RESULTS: The study included three articles involving patients with Sjogren
      syndrome subjected to dental implant treatment, representing a total of 12
      patients and 86 implants, with a mean pondered success rate of 86.33%. As regards
      ectodermal dysplasia, we included 14 articles, of which 11 corresponded to
      clinical series, two were reviews and one constituted a survey of dental
      professionals. The percentage success rate of the implants varied between 35.7
      100%. In relation to epidermolysis bullosa, we included 6 articles corresponding
      to clinical series, with a total of 16 patients and 92 implants, and a success
      rate between 75-100%. In the case of oral lichen planus we found only two
      articles corresponding to clinical case series, with a total of 5 patients and 14
      implants, and an implant survival rate of 100%. CONCLUSIONS: Based on our review
      of the literature, dental implant rehabilitation in patients of this kind is seen
      to be a valid treatment option, with a high percentage success rate. Long-term
      patient follow-up is essential in order to periodically monitor the condition of
      the disease and of the implants.

PMID- 21196862
TI  - Clinical study of hemodynamic changes during extraction in controlled
      hypertensive patients.
AB  - OBJECTIVE: To evaluate the efficacy and safety of the vasoconstrictor used in
      local anesthesia during dental extraction in controlled hypertensive patients.
      STUDY DESIGN: A prospective observational study was carried out in hypertensive
      patients (n=97) with a mean age of 60.45+/-9.60 years. The following parameters
      were monitored at three different timepoints (before the procedure, 3 minutes
      after local anesthesia infiltration, and 3 minutes after the operation): blood
      pressure (diastolic and systolic), heart rate, and oxygen saturation. Anesthesia
      (1-3 carpules) was provided in the form of articaine with 4% epinephrine as
      vasoconstrictor in one group, while another group received 3% mepivacaine without
      vasoconstrictor. RESULTS: All patients presented primary hypertension
      (n=97)(grade I in 57.7% of the cases and grade II in 42.3%). The most widely used
      antihypertensive drugs were angiotensin II receptor antagonists (ARA II). The
      only significant differences observed corresponded to systolic blood pressure
      measured before and after dental extraction in the group of hypertensive patients
      anesthetized with vasoconstrictor. CONCLUSIONS: In procedures such as dental
      extraction, no significant hemodynamic changes in well controlled hypertensive
      patients are seen attributable to anesthetic use with a vasoconstrictor, when
      fewer than three local anesthetic carpules are administered.

PMID- 21196863
TI  - Significance of pre-treatment panoramic radiographic assessment of edentulous
      patients--a survey.
AB  - OBJECTIVES: The present study was undertaken to review the significance of pre
      treatment panoramic radiographic assessment of edentulous patients, in the dental
      patient population of Haryana, India. STUDY DESIGN: In this study a total of 525
      completely edentulous patients were selected randomly. A panoramic radiograph was
      taken using Panoramic machine (Rotagraph plus) and all the radiographs were
      evaluated by 2 oral radiology specialists for the following clinically
      significant radiographic findings: retained root fragments, embedded teeth,
      radiolucencies, radiopacities and location of the mental foramen at the crest of
      the residual alveolar ridge. The data were analyzed using the chi square test.
      RESULTS: A total of 245 radiographic findings were seen in 168 (32%) patients.
      Out of total 525 cases 16.4% (n=86) patients had submucosal or intrabony root
      stumps, 4.8% (n=25) had embedded teeth, 2.5% (n=13) had radiolucencies, 9.9%
      (n=52) had radiopacities and 1.7% (n=9) had mental foramen at the crest of the
      residual alveolar ridge. CONCLUSION: The results of this study suggest that
      Routine radiographic examination of completely edentulous patients is critical
      before construction of complete denture.

PMID- 21196864
TI  - A clinical comparison of nano-crystalline hydroxyapatite (Ostim) and autogenous
      bone graft in the treatment of periodontal intrabony defects.
AB  - OBJECTIVES: The aim of the present study was to evaluate the efficacy of
      autogenous bone graft (ABG) and nano-crystalline hydroxyapatite (Ostim) in the
      management of human intrabony periodontal defects. STUDY DESIGN: Twenty-four
      similar two and three wall intrabony periodontal defects with >=5 mm probing
      depths and >=3 mm depths of intrabony component in 12 healthy patients were
      selected. One defect in each subject was treated with ABG (ABG group) and the
      contralateral one with ABG and Ostim (Ostim group). Plaque index (GI), gingival
      index (PI), clinical probing depth (CPD), clinical attachment level (CAL),
      gingival margin level, bone fill, crestal resorption and defect resolution were
      measured at baseline and during reentry surgery after 6 months. Wilcoxon signed
      rank test and Mann-Whitney U test were used to analyze the data. RESULTS: Groups
      showed statistically significant improvements in soft and hard tissue parameters
      after 6 months except in gingival margin level and crestal level. However, the
      between-group differences after 6 months were not statistically significant with
      regard to soft and hard tissue measurements. CONCLUSION: Within the limits of
      this study, both treatments resulted in marked clinical improvement, and Ostim
      treatment seemed to be effective in the treatment of two & three-wall intrabony
      defects as well as autogenous bone graft.

PMID- 21196865
TI  - Residual antibacterial activity of a new modified sodium hypochlorite-based
      endodontic irrigation solution.
AB  - OBJECTIVE: In this in vitro study the antibacterial substantivity of a new sodium
      hypochlorite-based root canal irrigant (Hypoclean) in bovine root dentin was
      investigated. STUDY DESIGN: Ninety dentin tubes prepared from bovine incisor
      teeth were used. After contamination for 14 days with Enterococcus faecalis, the
      specimens were divided into five groups as follows: Hypoclean; Tetraclean; 5.25%
      sodium hypochlorite (NaOCl); infected dentin tubes (positive control); and
      sterile dentin tubes (negative control). Dentin chips were collected with round
      burs into tryptic soy broth and after culturing, the number of colony-forming
      units (CFU) was counted. RESULTS: The number of CFU was minimum in the first
      cultures in all experimental groups, and the results obtained were significantly
      different from each other at any time period (P < 0.05). At all five experimental
      periods, the Tetraclean group showed the most effective antibacterial action (P <
      0.05). Regular 5.25% NaOCl group showed the worst result at all periods.
      Hypoclean group demonstrated no bacterial growth after treatment. In each group,
      the number of CFU increased significantly by time-lapse (P < 0.05). CONCLUSION:
      The residual antibacterial activity of Tetraclean was significantly greater than
      Hypoclean and 5.25% NaOCl.

PMID- 21196866
TI  - Periodontal disease and diabetes-Review of the Literature.
AB  - AIMS: To provide updated knowledge on the relationship between periodontal
      disease and diabetes from an oral health perspective. METHODS: A review of the
      English-language literature was performed, gathering articles on the two diseases
      published over the past 10 years. RESULTS: Both diseases result from the
      confluence of various triggering and modifying factors, and there are inter
      individual differences in the risk of their development. Recent research has
      shown that diabetes may increase the risk of periodontitis, and it has been
      proposed that chronic periodontal disease may influence the natural course of
      diabetes. There appears to be an association among oral infections, impaired
      sugar metabolism, and atherosclerosis, indicating a theoretical link between
      metabolic syndrome and periodontal disease. CLINICAL IMPLICATIONS: Control of
      periodontal disease may enhance glycemic control in patients with type 2
      diabetes. In turn, improved glycemic control may contribute to a better control
      of periodontal disease.

PMID- 21196867
TI  - Effects of Chamomilla recutita (L.) on oral wound healing in rats.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effect of Chamomilla
      recutita on the healing of ulcers in rats. STUDY DESIGN: A 5-mm wound was
      inflicted on the tongue of 36 rats. Treatment group animals were treated
      topically with 0.04 mL/day of chamomile ointment, whereas control group animals
      were not treated. Animals were sacrificed after 3, 7 or 10 days. Semi
      quantitative analysis of the degree of inflammation, fibroblast count and wound
      size was performed, as well as histometric analysis of re-epithelialization and
      percentage of collagen fibers of the lesion. RESULTS: Animals treated with
      chamomile showed the best results regarding epithelialization and percentage of
      collagen fibers after 10 days. As expected, time had a statistically significant
      effect (p < 0.05) on fibroblast count, epithelialization, inflammation and wound
      size; animals sacrificed at 3 days showed the worst results. CONCLUSIONS:
      Chamomile stimulated re-epithelialization and the formation of collagen fibers
      after 10 days of treatment; it did not, however, influence inflammation or
      fibroblast count.

PMID- 21196868
TI  - Prevalence of impacted premolars in a Turkish population and considerations for
      surgical treatment.
AB  - OBJECTIVE: The aim of this study was to identify the prevalence, associated
      pathology and symptoms, and treatment of impacted premolars in a Turkish
      population. STUDY DESIGN: This retrospective study examined panoramic radiographs
      and clinical records of 9,000 patients who presented consecutively at our oral
      and maxillofacial surgery clinics between January 1998 and January 2009. In
      addition to demographic data (patient sex and age), data was compiled on the
      number and location of impacted missing maxillary and mandibular premolars,
      retained deciduous molars, associated pathologies and symptoms, and treatment
      methods. RESULTS: A total of 105 impacted maxillary or mandibular premolars were
      observed in 93 patients (1.03%). Of these, 48 (51.6%) were female (age range: 13
      57 years) and 45 (43.4%) were male (age range: 13-58 years). Impacted mandibular
      second premolars accounted for 55.2% (n=58) of all impacted premolars. Migration
      was observed in only 11.83% of patients (n=11). Pathological changes and symptoms
      were noted in 15.05% of patients. CONCLUSION: Our results suggest that the
      prophylactic extraction of non-migrated impacted premolars may not be necessary.
      If the patient is cooperative, a "wait and see " approach may be preferable.
      Orthodontic or prosthetic treatment options should also be considered when
      planning treatment of non-migrated impacted premolars. Migrated impacted
      premolars should be kept under observation and should only be removed if they are
      associated with pathology or if extraction is required for prosthetic or
      orthodontic treatment.

PMID- 21196869
TI  - Cytotoxicity of a new hemostatic agent on human pulp fibroblasts in vitro.
AB  - OBJECTIVE: The objective of this study was to evaluate the cytotoxicity of the
      plant extract ankaferd blood stopper (ABS) in vitro. STUDY DESIGN: ABS was eluted
      with fresh Dulbecco's Modified Eagle's Medium (DMEM) without serum for 72 h, at
      37  degrees C. The cells treated with various dilutions of ABS were seeded into
      96-well microplate at 104/well in triplicates. Cells without treatment served as
      a control group. The number of viable cells after 48 h incubation was determined
      by a modified 3-(4, 5-dimethyl-thiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide
      (MTT) assay. The relative viability of pulp cells was expressed as color
      intensity of the number in the experimental wells relative to that of the control
      group. Absorbances were read at 570 nm on a microplate reader with a background
      subtraction at 620 nm. RESULT: The results showed that ABS was cytotoxic to human
      pulp fibroblasts by MTT assay. CONCLUSIONS: The influence of cytotoxicity to
      human pulp fibroblasts depended on concentration of ABS. The more dilutions
      exhibited less cytotoxic characteristics compared to the more concentrated forms.

PMID- 21196870
TI  - Evaluation of the immediate post-operative procedure after dental interventions.
      24 hours follow up study. Epico study.
AB  - OBJECTIVES: The purpose of this study was to make a descriptive approximation of
      the therapeutic management of the different dental interventions in clinical
      practice today, and to analyze the degree of consensus among the specialists
      participating in the study. STUDY DESIGN: A total of 447 odontologists,
      stomatologists or maxillofacial surgeons from 43 Spanish provinces participated
      in the study. The study sample consisted of patients aged 18 years old or over
      attending the clinic for a dental intervention. The type of intervention carried
      out and treatments administered before and after the intervention were recorded.
      At 24 hours after the intervention, intensity of pain experienced by the patient,
      rescue therapy administered for pain relief, sleep affectation, the appearance of
      adverse events or complications of the intervention, and treatment compliance
      were also recorded. RESULTS: Data corresponding to 4,194 patients were analyzed,
      of whom 53.2% were women (2,232). The mean age was 42.6 years (95%CI 42.2- 43).
      The most frequent interventions corresponded to: oral surgery (66.4%),
      endodontics (17.3%) and periodontal treatment (4.6%). A total of 43.2% of the
      patients were taking some medication before the intervention: anticoagulants
      (2.5%), antibiotics (33%), pain relief and/or anti-inflammatory agents (23%) and
      other drugs (7.6%); 16.6% were receiving combined treatment with antibiotics and
      analgesics and/or anti-inflammatory agents before the intervention. Treatments
      prescribed to the patient for the 24 hours following the intervention
      corresponded to only one analgesic and/or anti-inflammatory in 18%, and a
      combination of analgesics and/or anti-inflammatories in 77.1%. Antibiotics were
      prescribed in 39.7%. CONCLUSIONS: Different patterns of therapeutic management by
      the specialists were noted depending on the type of intervention carried out. The
      use of analgesics and/or anti-inflammatories depended on the severity of pain
      expected with each intervention and the administration of antibiotics was related
      to the prevention of local infections.

PMID- 21196871
TI  - The acromion thoracic flap: a reconstructive resource after exeresis of a parotid
      fibrosarcoma.
AB  - Sarcomas are rather uncommon in the salivary glands and have a high tendency
      towards recurrence. The treatment of choice is surgery, with the first surgical
      procedure being crucial, as the small size of the tumor is accompanied by the
      absence of post-surgery and post-radiotherapy fibrosis, which facilitates the
      surgery. The evident tendency towards recurrence makes it advisable to be radical
      in the exeresis. Often we have to consider a reconstructive period. Negative
      surgical margins increases the rates of local control. Treatment with
      radiotherapy is the complementary treatment indicated for patients with surgical
      margins less than 2 mm or positive. It has been observed that this treatment
      improves the local control of the illness. We present a case of parotid
      fibrosarcoma of a low grade of malignancy that was treated by means of
      parotidectomy and post-operative radiotherapy. The patient presented up to three
      recurrences, one of which required an acromion thoracic flap in order to
      reconstruct the surgical defect. Despite the treatment, the patient ended up
      dying because one of the recurrences was not operable.

PMID- 21196872
TI  - The expression of heat shock proteins 27 and 105 in squamous cell carcinoma of
      the tongue and relationship with clinicopathological index.
AB  - INTRODUCTION: In oral cavity, the tongue is the most common site prone to
      development of squamous cell carcinoma (SCC). Considering malignant
      transformation as a cellular stress, the expression of heat shock proteins (HSPs)
      may be affected in this process. In this study we assessed the expression of
      HSP105 and HSP27 as two of the most interested stress proteins and investigated
      their relationship with grade and stage of the tongue SCC. MATERIAL AND METHODS:
      Fifty-six specimens including 31 early and 25 advanced tongue SCC were gathered.
      All specimens were graded histologically from I to III. Sixteen sections of
      normal oral mucosa were used as control group. The cellularity and intensity of
      HSP105 and HSP27 expression were studied immunohistochemically in both case and
      control groups. Results were expressed by histochemical score (HSCORE). RESULTS:
      Significant differences were observed between expression of HSPs and stage of the
      disease. From early to advanced stage, the expression of HSP105 and HSP27
      increased and decreased, respectively. There was no relationship between
      histological grade of lesion and HSCORE of HSP105 expression (P=0.5), although,
      HSP27 expression had reverse relationship with the SCC histological grade.
      CONCLUSION: HSP27 and HSP105 may be indicated for prognostic purposes in
      evaluation of tongue SCC. HSP 27 may be used for more accurate microscopic
      grading of tongue SCC. Increased expression of HSP105 in advanced stage may lead
      to using this protein for immunotherapy of tongue SCC.

PMID- 21196873
TI  - Calculation of bone graft volume using 3D reconstruction system.
AB  - OBJECTIVES: To obtain bone bioreplicas for determining precisely the amount of
      biomaterial required for bone regeneration procedure. STUDY DESIGN: A case
      control comparison with a total sample size of 20 cases, 10 control and 10 test
      samples. Bioreplicas were generated from helical CAT scans with 0.5 mm slices,
      without 3D reconstruction or image filters. Bone defects in premolar and molar
      areas were treated with titanium mesh and xenograft (MP3) combined with
      resorbable carriers. Time taken to carry out procedures with and without the use
      of bioreplicas (in minutes), discrepancies between the grafts performed with and
      without bioreplicas and bone defects (mm), and postoperative complications were
      registered. RESULTS: No significant differences were recorded for measurements of
      width and length of bone defect between patient bone and the biological models.
      CONCLUSIONS: The use of bioreplicas obtained by rapid prototyping is effective in
      treatment planning.

PMID- 21196874
TI  - Bolton's intermaxillary tooth size ratios among Iranian schoolchildren.
AB  - OBJECTIVES: The aims of the present study were to determine anterior and total
      tooth-width ratios in a representative Iranian sample in Tabriz city and compare
      them with the Bolton standards. STUDY DESIGN: A total of 54 Iranian
      schoolchildren (12-14 years old) in Tabriz were examined. Alginate impressions
      were taken for subjects and poured by the dental stone. The mesiodistal widths of
      the teeth were measured using a digital caliper. The overall and anterior Bolton
      's intermaxillary tooth size ratios for each model pair was calculated. RESULTS:
      There were no significant differences (p > 0.05) between the right and left sides
      of the dental arch and a symmetry in size exists. There were no significant
      differences between genders for all teeth measured except for the maxillary
      central incisors, maxillary canines and mandibular canines. Anterior and overall
      Bolton ratios for males were 77.72+/-0.25 and 92.44+/-0.19 and for females were
      78.48+/-0.30 and 92.45+/-0.23 percent, respectively. There were no statistically
      significant differences between males and females for the anterior and overall
      ratios. The anterior and overall Bolton ratios among Tabrizian schoolchildren
      were 78.10+/-0.28 and 92.24+/-0.21 percent, respectively. There was no
      statistically significant difference between these ratios and those were found in
      the Bolton study. CONCLUSION: No significant differences between the mesiodistal
      sizes of contralateral teeth were observed and a symmetry in size exists. There
      were no significant differences in the mesiodistal sizes of similar teeth between
      males and females except for the maxillary central incisors, maxillary canines
      and mandibular canines. Significant differences in Bolton ratio between males and
      females, and examined population (student from Tabriz, Iran) and the Bolton's
      weren't observed either.

PMID- 21196875
TI  - Prevalence of herpes simplex, Epstein Barr and human papilloma viruses in oral
      lichen planus.
AB  - OBJECTIVES: The aim of the present study was to assess the prevalence of Herpes
      Simplex virus, Epstein Barr virus and Human Papilloma virus -16 in oral lichen
      planus cases and to evaluate whether any clinical variant, histopathological or
      demographic feature correlates with these viruses. STUDY DESIGN: The study was
      conducted on 65 cases. Viruses were detected immunohistochemically. We evaluated
      the histopathological and demographic features and statistically analysed
      correlation of these features with Herpes Simplex virus, Epstein Barr virus and
      Human Papilloma virus-16 positivity. RESULTS: Herpes Simplex virus was positive
      in six (9%) cases and this was not statistically significant. The number of
      Epstein Barr virus positive cases was 23 (35%) and it was statistically
      significant. Human Papilloma virus positivity in 14 cases (21%) was statistically
      significant. Except basal cell degeneration in Herpes Simplex virus positive
      cases, we did not observe any significant correlation between virus positivity
      and demographic or histopathological features. However an increased risk of
      Epstein Barr virus and Human Papilloma virus infection was noted in oral lichen
      planus cases. CONCLUSIONS: Taking into account the oncogenic potential of both
      viruses, oral lichen planus cases should be detected for the presence of these
      viruses.

PMID- 21196876
TI  - The cytotoxicity of resin composites cured with three light curing units at
      different curing distances.
AB  - OBJECTIVE: The purpose of this study was to compare the effect of light curing
      distance on the cytotoxicity of five resin composites cured with three high-power
      light curing units. STUDY DESIGN: Seven cylindrical discs of each material
      (Grandio(r), Voco; FiltekTM Z250, 3M ESPE; ClearfilTM AP-X, Kuraray Co. Ltd.;
      AeliteTM LS, Bisco Inc. and Simile(r), Pentron) were cured. For curing, soft-up
      mode of quartz-tungsten-halogen, exponential mode of light emitting diode for 20
      s, and ramp-curing mode of plasma arc light curing units for 6 s were used. The
      curing tip distances were determined as 2 and 9 mm and controlled via the use of
      metal rings. After ageing the samples for 24 and 72 hours in Dulbecco's Modified
      Eagle Medium/Ham's F12 (DMEM/F12), cytotoxicity of the extracts to cultured
      fibroblasts (L 929) was measured by using MTT (tetrazolium salt 3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. The degree of
      cytotoxicity for each sample was determined according to the reference value
      represented by the cells in a pure culture medium. Statistical significance was
      determined using multifactorial analysis of variance. RESULTS: The type of resin
      composite (p <0.05), light curing unit (p <0.05), curing tip distance (p <0.05)
      and evaluation period factor (p <0.05) had statistically significant cytotoxic
      effects on L-929 mouse fibroblast cells. However, when the tested materials
      polymerized at both distances (2 mm and 9 mm) in both evaluation periods (24 h
      and 72 h), there was no significant difference in the mean CSR% values obtained
      when the quartz-tungsten-halogen, light emitting diode and plasma arc light
      curing units were used (p=0.184, F=1.448). CONCLUSIONS: The results of this study
      suggest that the light curing units and resin composites should be harmonized to
      one another and the curing distance between the tip of the light curing unit and
      the restoration surface should be as close as possible in order to achieve
      maximal biocompatibility.

PMID- 21196877
TI  - Factors associated with complications of removal of third molars: a transversal
      study.
AB  - OBJECTIVES: The purpose of this study is to estimate the overall frequency of
      complications associated with third molars (M3) removal and to identify the risk
      factors associated with these complications. STUDY DESIGN: To the transversal
      analysis, a researcher confidentially reviewed the records of all M3 surgery
      patients. The predictor variables were demographic (i.e. age and gender),
      localization and position of third molar, bone removal and tooth sectioning.
      RESULTS: 210 patients had one or more third molars teeth removed, a total of 605
      teeth. The sample's mean age was 21.6+/-9.2 years, with 1,4 woman to 1 man.
      Postoperative complications were recorded in 54 extractions of third molars. The
      most common complications were infection (42.6%), followed by radicular fractures
      (11.1%) and gingival alterations (11.1%). Complications were significantly
      affected by 3 factors: age over 25 years old (p=0.002--OR 2.21), location
      (p=0.006--OR 2.36), bone removal (p=0.002--OR 3.03) and tooth sectioning
      (p=0.00002--OR 3.59). CONCLUSIONS: The results of these analyses suggest that
      age, location of the tooth, bone removal and tooth sectioning appear to be
      associated with a higher complication rate for M3 extractions.

PMID- 21196878
TI  - Marginal bone loss in relation to the implant neck surface: an update.
AB  - A review is made of the publications on the marginal bone loss of implants with a
      polished neck, rough neck with microthreading, and rough neck without
      microthreading. A PubMed search was carried out with the following key words:
      machined neck implant, polished neck implant, marginal bone loss, covering the
      period between January 1998 and March 2009. Inclusion was limited to those human
      clinical studies involving a minimum follow-up of 12 months, and registering the
      level of bone loss from the time of placement of the implant or prosthetic
      restoration to the end of follow-up. For most of the authors there were no
      significant differences in marginal bone loss between polished neck and rough
      neck implants. On the other hand, implants with a rough neck and microthreading
      showed significantly less bone loss than those with a polished neck or with a
      rough neck without microthreading. The survival rate of the implants with a
      polished neck ranged from 87% to 97.7%, versus 94.5% to 100% for those with a
      rough neck, and 100% for the rough neck implants with microthreading. No peri
      implant disease was registered in the different studies.

PMID- 21196879
TI  - Lip squamous cell carcinoma in a Brazilian population: epidemiological study and
      clinicopathological associations.
AB  - OBJECTIVES: It was evaluated epidemiological aspects of primary lip squamous cell
      carcinoma (LSCC) and its associations with clinicopathological factors. STUDY
      DESIGN: This retrospective, cross-sectional study analysed a socio-demographic,
      clinical, and morphological data of HNSCC in a Brazilian population (n=30). Data
      analysis included descriptive statistics and bivariate analyses using the chi
      square and Fisher 's exact tests to compare the variables. RESULTS: The LSCC
      represented 10.8% of all oral cavity squamous cell carcinoma. Lip malignant
      disease was more prevalent in elderly men, with male-to-female ratio of 5:1.
      Lower lip was more affected. It was observed high rates of chronic solar
      exposure, and tobacco and alcohol drinking habits. Clinically, early TNM staging,
      small tumour lesions, and non-metastatic disease were predominant findings. It
      was identified a high frequency of well differentiated tumor samples. Worse
      Karnofsky performance status was associated with cervical metastasis.
      CONCLUSIONS: Our findings showed that LSCC patients exhibited similar
      epidemiological and clinical profiles as noted in other studies. Still, the
      occurrence of metastatic disease was associated with a worse physical performance
      status of the LSCC patients during diagnosis.

PMID- 21196880
TI  - Pediatric oral ranula: clinical follow-up study of 57 cases.
AB  - OBJECTIVE: To present 57 cases of oral ranula in children, analyzing the clinical
      characteristics, treatment and outcome of these lesions. METHODS: The clinical
      histories of patients diagnosed with oral ranula, seen between 1998 and 2008 at
      the Oral and Maxillofacial Surgery Unit of a reference Children 's Hospital (0-14
      years) were reviewed. All patients with clinical diagnosis of oral ranula were
      included. RESULTS: Fifty-seven patients, 21 boys and 36 girls, with a mean age of
      5.1 years were included in the study. Thirty-two cases were located on the left
      side of the floor of the mouth. The lesion diameter varied between 1 and 3 cm in
      27 cases, 22 were less than 1 cm, and 8 were larger than 3 cm. Fifty-four cases
      were asymptomatic and 3 ranulas had pain on swallowing. Twenty-two cases were
      resolved by opening with a tract dilator and 35 by marsupialization. Seven cases
      recurred at a mean of 12 months after treatment, three of these from the
      marsupialization group. CONCLUSION: The majority of the oral ranulas occurred in
      females, asymptomatic, on the left side of the floor of the mouth, with a mean
      size of 1 to 3 cm; all lesions were treated by surgery, of which 7 recurred.

PMID- 21196881
TI  - Immunohistochemical expression of Bcl-2 in benign and malignant salivary gland
      tumors.
AB  - OBJECTIVES: The present study was undertaken to assess and compare the
      immunohistochemical expression of Bcl-2 in selected benign and malignant salivary
      gland tumors. STUDY DESIGN: A total of 50 cases of buffered formalin-fixed,
      paraffin embedded tissues of previously diagnosed cases of benign and malignant
      salivary gland tumors from the archives of Department of Oral and Maxillofacial
      Pathology and Microbiology, SDM College of Dental Sciences and Hospital, Dharwad,
      India, were taken for the study. The immunohistochemical staining procedure was
      performed using monoclonal anti Bcl-2 antibody, as directed by the manufacturer.
      RESULTS: Thirty six cases (72%) out of 50 cases showed a positive expression for
      Bcl-2. Benign salivary gland tumors showed a positive expression in 8 out of 14
      cases (~57%) and malignant salivary gland tumors in 28 out of 36 cases (~78%).
      The staining was intense in the normal lymph node, which is used as a positive
      control. Bcl-2 expression was seen in both benign and in malignant salivary gland
      tumors taken for the study except in "canalicular adenoma". CONCLUSION: The
      immunohistochemical expression of Bcl-2 was greater and more intense in malignant
      salivary gland neoplasms, suggesting a high survival rate of tumor cells in
      malignant neoplasms.

PMID- 21196882
TI  - Leukocyte adhesion deficiency type I--a focus on oral disease in a young child.
AB  - This paper presents a case of the moderate form of Leukocyte adhesion deficiency
      type 1 (LAD-1) in a 4 year-old boy. LAD-1 is a rare, inherited immunodeficiency
      that affects 1 in 1 million people yearly. Affected patients are susceptible to
      recurrent bacterial and fungal infections, impaired pus formation and delayed
      wound healing. In the oral clinical finding, more important is a generalized
      prepuberal periodontitis that can affect the primary and permanent dentitions.
      For this reason cooperation between dentists and pediatricians is essential in
      these patients. Evaluating immune system in these patients included peripheral
      blood leukocyte counts, measurement of serum immunoglobulin levels, assessment of
      complement level and function, flow cytometric analysis of lymphocyte subsets,
      and tests of phagocytic function (nitrobluetetrazolium test (NBT)). In families
      with known molecular defect, an earlier prenatal diagnosis is possible by
      chorionic villi biopsy. The most important focus should be to control infections.
      Treatment includes systemic antibiotics and in many cases bone marrow
      transplantation.

PMID- 21196883
TI  - Meta-analysis on the survival of short implants.
AB  - OBJECTIVE: To evaluate the success and failure rates of short implants (10 mm or
      less) for oral rehabilitations in cases of limited bone height. STUDY DESIGN:
      Review of the articles published on the topic between the years 2000 and 2010,
      and development of a descriptive meta-analysis of the results. RESULTS: The
      majority of the studies obtain a cumulative success rate (CSR) similar to that of
      longer implants (92.5%-98.42% for machined and rough-surface implants,
      respectively). The studies that record lower cumulative success rates (CSR) are
      later studies that analyze implants with a machined surface. Almost none of the
      studies compared the success/failure rates with the bone quality or location of
      the implant (maxilla or mandible). Thus, the results obtained are from a mixture
      of these parameters. CONCLUSIONS: In view of the results analyzed,
      rehabilitations with short implants are a reliable treatment; however, the lack
      of consistency in the study designs as well as the presence of bias in all of the
      studies reviewed make it difficult to analyze the data.

PMID- 21196884
TI  - Immediate post-extraction implants subject to immediate loading: a meta-analytic
      study.
AB  - Since Branemark first started developing its implant system, there has been a
      continuous and significant evolution in oral implantology through experimental
      and clinical research, and many of the concepts that were once considered valid
      have now become the subject of debate. The insertion of the implant immediately
      after extraction of the tooth to be substituted has now become the implant
      treatment of choice and is associated with preserving the bone structure and the
      gingival architecture, as well as with reducing the treatment time, which
      ultimately benefits the patient. OBJECTIVE: To evaluate the success rate of the
      immediate post-extraction implants (IPI) subject to immediate loading. STUDY
      DESIGN: A meta-analytic study was carried out on 659 immediate post-extraction
      implants obtained from a bibliographic review of 25 articles published within the
      last 9 years. RESULTS: We obtained a sample of 322 patients who had been treated
      with a total of 659 implants placed immediately following extraction. The mean
      age of the patients was 51 years old. A total of 441 implants were inserted in
      the maxilla, 152 in the mandible and 64 were placed in an unspecified location.
      The survival rate ranged between 85% and 100%. CONCLUSIONS: Immediate post
      extraction implant treatment is an implant alternative with a survival rate
      similar to that of the conventional technique for implant placement and enables
      preserving both the bone structure and gingival architecture, as well as
      providing immediate functional loading, thus improving the quality of the
      treatment as far as the patient is concerned.

PMID- 21196885
TI  - Detection of AA-type amyloid protein in labial salivary glands.
AB  - OBJECTIVES: Among the diverse forms of amyloidosis, secondary type is the most
      frequent one. Diagnosis of amyloid deposition is based on the identification of
      the fibrillary protein amyloid by means of Congo Red (CR) or crystal violet (CV)
      stains, but these techniques do not differentiate between the different types of
      amyloid fibrils. The aim of this study was to identify by immunofluorescence (IF)
      AA amyloid a pathological fibrillar low-molecular-weight protein formed by
      cleavage of serum amyloid A (SAA) protein in labial salivary gland (LSG) biopsies
      from patients with secondary amyloidosis. STUDY DESIGN: 98 LSG were studied, 65
      were from patients with secondary amyloidosis and 33 from subjects with chronic
      inflammatory diseases without evidence of this anomaly. All sections were stained
      with hematoxylin and eosin (H &E), CV, CR and IF using anti-AA antibodies.
      Positive and negative controls were used for all techniques. RESULTS: CV and CR
      demonstrated that the amyloid substance was found mainly distributed periductally
      (93.8%), followed by periacinar and perivascular locations (p <0.001); however,
      the IF demonstrated that amyloid AA substance predominates in the periacinar area
      (73.8%), followed by periductal and perivascular locations (p <0.001). IF has a
      sensitivity of 83%, 100% of specificity, 100% of predictive positive value and
      75% of predictive negative value. CONCLUSIONS: The results of this study confirm
      the efficacy of the LSG biopsy as a highly reliable method for diagnosis of
      secondary amyloidosis.

PMID- 21196886
TI  - IL-10 and IL-10 receptor overexpression in oral giant cell lesions.
AB  - OBJECTIVE: Central giant cell lesions (CGCL) and peripheral giant cell lesions
      (PGCL) occur in the jaws and contain osteoclast-like giant cells and mononuclear
      cells positive for the macrophage marker CD68. The participation of immune
      inflammatory mechanisms has been proposed in the lesions development. As IL-10 is
      one of the most important anti-inflammatory cytokines and it is also an
      inhibitory cytokine to macrophage function and bone resorption, the purpose of
      the present study was to investigate its expression together with its receptor
      (IL-10Ralpha) in CGCL and PGCL. STUDY DESIGN: Six fragments of CGCL and seven
      fragments of PGCL were obtained by surgical excision. Frozen specimens were cut
      and subjected to immunofluorescence staining using fluorescent-labeled anti-CD68,
      anti-IL-10, and anti-IL-10Ralpha monoclonal antibodies. Microscopic analyses were
      performed and the percentage of positive mononuclear and giant cells for each
      parameter was obtained. RESULTS: Our results revealed that all giant cells from
      CGCL and PGCL were CD68+ and IL-10Ralpha+ and that the majority was also positive
      for IL-10. More than 50% of the mononuclear cells from both lesions expressed IL
      10Ralpha and the majority of these cells were CD68+ and IL-10+. CONCLUSION:
      Considering that IL-10 has inhibitory effects on the pathologic processes related
      to the development of the oral giant cell lesions, the high frequencies of cells
      producing this cytokine seems contradictory to these lesions growth.
      Investigation about the production of inflammatory cytokines as well as the IL-10
      signaling pathways in oral giant cell lesions is required to elucidate the
      immunopathology of CGCL and PGCL.

PMID- 21196887
TI  - Bone regeneration using particulate grafts: an update.
AB  - OBJECTIVE: A review is made of the publications on bone regeneration using
      particulate grafts, with an evaluation of the success of implants placed in such
      regenerated areas. MATERIAL AND METHOD: A Medline search using different key
      words was made of the articles published between 1999-2009 involving at least two
      patients subjected to grafting with autologous, homologous or xenogenic bone, non
      bony substitutes, or a combination of these grafts for the placement of dental
      implants. Studies involving block grafting were excluded. A total of 11 studies
      were evaluated. RESULTS: These grafts are indicated in cases of small or peri
      implant bone defects such as dehiscences and fenestrations, with the possibility
      of combining a barrier membrane. However, some authors have used particulate
      block grafts to secure vertical or horizontal increments of the alveolar process.
      In most of these cases, graft healing until implant placement lasted 6-9 months.
      The most frequent complications in the receptor zone were wound dehiscences with
      exposure of the membrane. In almost all cases, prosthetic loading of the implants
      took place more than three months after their placement. The implant survival
      rate varied from 90.9% to 100%, with an implantation success rate of 85.7% to
      100%. CONCLUSIONS: Although our sample is small, due to the difficulty of finding
      homogeneous studies, it can be concluded that particulate grafts are effective in
      correcting localized defects of the alveolar process. The complications of
      particulate grafting are few, and the success rate of implants placed in the
      reconstructed areas varies from 85.7% to 100%.

PMID- 21196888
TI  - Influence of cavity preparation technique (rotary vs. ultrasonic) on microleakage
      and marginal fit of six end-root filling materials.
AB  - OBJECTIVES: To evaluate in vitro the effect of cavity preparation with microburs
      and diamond-coated ultrasonic tips on the microleakage and marginal fit of six
      end-root filling materials. STUDY DESIGN. The following materials were assessed:
      amalgam (Amalcap), zinc oxide eugenol (IRM), glass ionomer (Vitrebond), compomer
      (Cavalite), mineral particle aggregate (MTA) and composite (Clearfil). Cavity
      preparation was performed with microburs or diamond ultrasonic tips in single
      root teeth. The seal was evaluated in two experiments: a microleakage assay on
      the passage of dye to the interface; and a scanning electron microscopy study and
      analysis of epoxy resin replicas, measuring the size of gaps in the interface
      between filling material and cavity walls. Multifactorial ANOVA, multiple
      comparison test and Student 's t test were used for statistical analyses of the
      data, considering p <0.05 to be significant. RESULTS: Clearfil and MTA achieved a
      hermetic seal. Leakage and interface gap size was greater with Cavalite than with
      Clearfil and MTA, followed by Vitrebond and IRM. The worst seal was obtained with
      Amalcap. The use of diamond-coated ultrasonic tips improved the seal and reduced
      the gap when using materials that did not hermetically seal the cavity (Amalcap,
      IRM, Cavalite, Vitrebond). The preparation technique did not affect materials
      that achieved a hermetic seal (Clearfil, MTA). CONCLUSIONS: Clearfil and MTA
      obtained a hermetic seal due to their excellent marginal fit and are the most
      recommended materials for clinical use, taking account of their sealing capacity.
      Ultrasonic cavity preparation is preferable because it improves the seal and
      marginal fit of materials that do not achieve a hermetic seal of the cavity
      (Amalcap, IRM, Cavalite, Vitrebond).

PMID- 21196889
TI  - Interleukins IL-6, IL-8, IL-10, IL-12 and periimplant disease. An update.
AB  - INTRODUCTION: A study is made of the usefulness of cytokines (such as interleukin
      6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) and interleukin-12 (IL
      12)) as markers of periimplant disease (mucositis and periimplantitis). An
      increase in the levels of these cytokines in dental implant crevicular fluid may
      give rise to a lack of osteointegration, bone loss or implant failure. OBJECTIVE:
      To review the literature relating IL-6, IL-8, IL-10 and IL-12 levels to dental
      implant surgery and periimplantitis. MATERIAL AND METHOD: A PubMed literature
      search was made of articles in English and Spanish, using the key words "cytokine
      and dental implants", cytokine and periimplantitis", "IL-6, IL-8, IL-10, IL-12
      and dental implants", "IL-6, IL-8, IL-10, IL-12 and periimplantitis". Fourteen
      articles were found and classified into two groups relating interleukin levels
      to: a) periimplant disease; and b) their influence upon dental implant
      osteointegration without periimplant disease. CONCLUSIONS: An increase in
      interleukin levels is observed in patients with periimplant disease, though there
      is controversy over the effect of interleukins in crevicular fluid and
      periimplantitis in relation to implant failure or the development of periimplant
      disease.

PMID- 21196890
TI  - Investigation of interleukin-1 alpha and interleukin-6 expression and interleukin
      1 alpha gene polymorphism in keratocystic odontogenic tumors and ameloblastomas.
AB  - OBJECTIVE: In jawbones, ameloblastomas and odontogenic keratocysts share many
      clinical features in common such as aggressiveness, high recurrence rates and
      radical management options. Understanding the pathogenesis and biological aspects
      of these tumors would improve the success of diagnose and treatment procedures.
      The aim of this study was to exhibit the reasons of high recurrence rates and
      growth potentials of ameloblastomas and keratocystic odontogenic tumours by
      investigating the expression of IL-1alpha and IL-6 and IL-1alpha -889 gene
      polymorphism. IL-1alpha and IL-6 are shown as very effective tissue degrading
      factors in bone remodelling. STUDY DESIGN: This study included 25 cases of
      ameloblastomas, 41 cases of keratocystic odontogenic tumors (parakeratinized
      odontogenic keratocysts) and 8 cases of orthokeratinized odontogenic keratocysts.
      All histological slides were stained immunohistochemically to show the expression
      of IL-1alpha and IL-6. Restriction fragment length analysis was used to
      investigate the cytokine gene polymorphism. RESULTS AND CONCLUSIONS: The higher
      expression rates of IL-1alpha and IL-6 were associated with tumor size in
      ameloblastomas and with cyst wall thickness in keratocystic odontogenic tumors.
      This finding suggested us that the cytokines IL-1alpha and IL-6 play a role on
      aggressive behaviour of ameloblastomas and keratocystic odontogenic tumors by
      making easy bone resorption. In addition, IL-1alpha (-889) T polymorphism was
      found consistent with increased IL-1alpha expression but not seem as a risk
      factor on the development of these tumors.

PMID- 21196891
TI  - Risk factors associated with early failure of dental implants. A literature
      review.
AB  - The aim of the study was to examine articles published on risk factors associated
      with early failure of dental implants. We conducted a search on PubMed for
      articles published between January 2000 and December 2009 using the keywords
      'dental implants' and 'early failure'. Seven studies that specified the number of
      early failed implants and studied the associated risk factors were included.
      Early failures are caused by the inability of tissue to establish
      osseointegration prior to prosthetic restoration; however the causal factors and
      mechanisms are unclear. In the reviewed literature there was a higher percentage
      of early than late failures; nevertheless, few articles were found that analyzed
      risk factors associated with early implant failure. In the majority of studies,
      statistically significant factors associated with early implant failure were
      smoking, quantity and quality of bone, and posterior implant location. The low
      number of studies in the literature does not allow definitive conclusions to be
      drawn.

PMID- 21196892
TI  - Immunohistochemical expression of pRb in pleomorphic adenoma and carcinoma ex
      pleomorphic adenoma.
AB  - OBJECTIVE: This study aimed to characterize alteration in the immunohistochemical
      expression of pRb in normal tissue of the salivary gland surrounding pleomorphic
      adenoma, the tumor cells of pleomorphic adenomas, and carcinoma arising in
      pleomorphic adenoma. STUDY DESIGN: A selected series of 29 cases of pleomorphic
      adenomas, and 27 cases of carcinoma ex-pleomorphic adenoma (undifferentiated and
      adenocarcinoma types) were examined. RESULTS: The results showed that pRb
      expression was negative in the components of normal tissue of the salivary gland
      surrounding pleomorphic adenoma. PRb expression in pleomorphic adenomas shows
      that 2 cases out of 29 (6.9%) strongly expressed in the duct cells, 7/29 (24.1%)
      cases showed moderate staining. pRb nuclear staining in myxochondroid was
      identified in 10/29 (34.5%) cases of pleomorphic adenomas with weak staining,
      6/29 (20.7%) with moderate staining. pRb was strongly expressed in carcinoma
      cells in 19 out of 27 cases (70.4%). CONCLUSION: This study suggests the
      alteration of pRb expression would increase from pleomorphic adenoma to carcinoma
      arising in pleomorphic adenomas (6.9% versus 70.4%).

PMID- 21196893
TI  - Fluoride concentration and pH of pediatric medicines regularly and long-term used
      by children.
AB  - OBJECTIVES: Our aim in this study was to determine the fluoride concentration and
      pH of 71 pediatric medicines regularly and long-term used by children. STUDY
      DESIGN: The fluoride concentration was evaluated by selective electrode of
      fluoride (Orion). The pH was confronted using specific electrode (Orion) coupled
      to a potentiometer (Orion). The analyses were accomplished in duplicate. Pearson
      's correlation and Kruskal-Wallis test were used. P-values below 5% were
      considered statistically significant. RESULTS: Medicine pH averages+/-SD varied
      from 2.3+/-0.01 to up 10.6+/-0.02. Values below critical pH were observed in
      42.25% (n=30) of presentations, with 25.35% (n=18) below 4.5 pH. Most medicines
      (84.5%) presented fluoride concentration below 0.05 mg/L. CONCLUSIONS: Among the
      pediatric medicines evaluated, this study has showed that 2-4 times-a-day
      posology and syrup formulations presented lowest pH and fluoride concentration,
      resulting in factors that predict highest cariogenic and erosive potential.

PMID- 21196894
TI  - Efficacy of a bioactive alloplast, in the treatment of human periodontal osseous
      defects-a clinical study.
AB  - Presently, bone replacement grafts are one of the modalities of therapy for which
      there is histologic evidence of regeneration coronal to the base of the previous
      osseous defect. Bioactive glasses are used extensively in medicine and dentistry.
      This study evaluated the additional efficacy of a bioactive alloplast, Perioglas,
      in comparison with open flap debridement only. 8 systemically healthy volunteers
      were chosen, each having 2 collateral sites with >=6 mm clinical probing depth
      and radiographic evidence of an intrabony defect. Randomly, one defect was
      treated with open flap debridement plus bioactive glass (test) and the other with
      open flap debridement alone (control). At baseline, 3, 6, 9 months measurements
      were recorded which included plaque index, gingival index, pocket probing depth,
      clinical attachment level, and increase in gingival recession. Standardized
      radiographs were used to measure defect fill and alveolar crest resorption. The
      data were subjected to statistical analysis. Both treatments showed no
      significant differences between the two groups at any point of time. However,
      radiographically, bioactive glass group showing significant improvement in bone
      fill over the sites treated with open flap debridement alone. The alloplastic
      bone graft material, PerioGlas, demonstrated clinical advantages beyond that
      achieved by debridement alone.

PMID- 21196895
TI  - Effect of chin position on natural head orientation reproducibility.
AB  - BACKGROUND AND AIMS: Establishment of natural head position (NHP) in radiography
      or photography by estimation, which is called natural head orientation (NHO), has
      been recently advocated by various studies. This study aimed to determine the
      effect of chin position on the accuracy and reproducibility of NHO in a more
      realistic way. MATERIALS AND METHODS: NHP-based digital photographs of 33 adults
      with normal profile were modified using the computer software Supper-Goo and
      Photoshop technique to produce 99 profile images in three groups with normal,
      forward and backward chin positions. The reconstructed images were presented to
      three observers who rotated the images through a circular hole on a computer
      monitor. The horizontal angle was read on screen and recorded whenever they found
      the best horizontally-oriented face. This was performed at four intervals: T0:
      baseline; T1: after 5 minutes; T2: after one week; and T3: one month after
      baseline. RESULTS: After orientation, the mean orientation angles were 0.19
      degrees +/-1.39, 0.20 degrees +/-1.53 and -0.31 degrees +/-1.38 for the normal,
      forward and backward chin groups, respectively. T-test did not show any
      significant differences in NHO and NHP among the three groups of chin position: P
      values of 0.17, 0.19, and 0.26 for normal, forward, and backward chin positions,
      respectively. However, one-way ANOVA demonstrated significant differences in the
      NHO between the normal and backward, and backward and forward chin groups. The
      obtained reproducibility rate of NHO calculated via Med-Calc 8.1 online software
      for T0, T1, T2 and T3 intervals was more than 60%, which is regarded significant
      in medical studies. CONCLUSION: Natural head position could be created with great
      reproducibility through orientation of profile images in different chin
      positions. NHO is under the influence of chin position; however, this influence
      is not clinically significant.

PMID- 21196897
TI  - Prevalence of polyomaviruses BK, JC, SV40, KI, and WU in non-malignant tonsil
      specimens.
AB  - AIM: The recently described polyomaviruses KI and WU have been detected in
      respiratory samples, stools, tonsils, and blood, particularly in
      immunocompromised conditions, although little is known about tissue tropism.
      Herein we investigated the occurrence of KIV and WUV in non-malignant tonsillar
      specimens by Real-time quantitative PCR; the presence of polyomaviruses BK, JC
      and SV40-DNA was also evaluated. METHODS: Twenty-nine non-malignant tonsil
      specimens obtained from children and adults admitted for tonsillectomy were
      prospectively studied. Real-time quantitative TaqMan PCR for polyomaviruses KI,
      WU, BK, JC, and SV40 were performed. RESULTS: KI-DNA was positive in 2/29
      tonsillar specimens (6.9%), while BK- DNA, JC-DNA, SV-40 DNA, and WU-DNA
      sequences were not identified. CONCLUSION: Few studies have investigated the
      prevalence of polyomaviruses in tonsil specimens, with varying results, and data
      are particularly scant as regards the newly discovered KIV and WUV. Two major
      questions remain to be definitely answered at this regard: the possibility that
      human tonsils represent the initial site of infection and/or a latency site and
      the biological and clinical meaning of KIV and WUV in different contexts and
      groups of patients, in that it is not clear whether they are simple bystanders or
      play a role in tonsil disease.

PMID- 21196896
TI  - Pharmacokinetics and efficacy of intravenous or intramuscular hepatitis B
      immunoglobulins in prophylaxis of hepatitis B after liver transplantation.
AB  - AIM: The use of hepatitis B immunoglobulin (HBIg) combined with nucleos(t)ide
      analogues (NUCs) has improved outcomes in post-hepatitis B (PHB) liver transplant
      (LT), reducing the 1-year recurrence rate below 10%. The aim of this study was to
      evaluate efficacy and pharmacokinetics of prophylaxis with NUC(s) and intravenous
      (iv-) or intramuscular (im-) HBIg in 33 PHBLTs, transplanted for more than 1
      year. METHODS: During the first six months of the study, 18 subjects received
      5000 IU of iv-HBIg every four weeks and 15 patients 2160 IU/12 mL of im-HBIg
      every two weeks. In the following six months, 31 subjects were switched to two
      different concentrations of im-HBIg, 2160/12 mL (16 patients) or 2000 IU/6 mL
      every two weeks (15 patients). RESULTS: All patients remained HBsAg-negative and
      30/31 maintained anti-HBs >100 IU/L. Overall mean anti-HBs titer during treatment
      was 363 IU/mL. Mean HBIg half-life was 21.4, 27.3 and 26 days with intravenous,
      diluted or concentrated im-preparations, respectively. CONCLUSION: These results
      confirm an analogue efficacy and tolerance of iv- and im-HBIg combined with
      antivirals in prophylaxis of hepatitis B after LT. Anti-HBs titers three times
      higher than aimed and four weeks mean half-life could suggest the reduction of
      doses and the elongation of the interval of administration of im-HBIg.

PMID- 21196898
TI  - Hepatocellular carcinoma at the cutting edge of science and practice.

PMID- 21196899
TI  - Imaging of hepatocellular carcinoma and early diagnosis.
AB  - The incidence of hepatocellular carcinoma (HCC) is steeply rising in
      industrialized nations, and the vast majority of patients do not qualify for
      curative treatment at the time of diagnosis. This phenomenon is directly related
      to the clinician's ability to accurately diagnose HCC at an early stage, which
      can be quite challenging in the setting of a cirrhotic, nodular liver. A
      particular difficulty arises in the differentiation of very small neoplastic
      lesions from hyperplastic nodules. In the past decade, technological advances
      have made dynamic imaging of the cirrhotic liver more feasible, which in turn
      improves the sensitivity and specificity of these modalities for the diagnosis of
      HCC. In this article we describe the typical characteristics of HCCin modalities
      such as ultrasound, computed tomography, and magnetic resonance imaging, discuss
      the recent advances in dynamic imaging in each of these modalities, and review
      the published guidelines for surveillance and diagnosis for HCC.

PMID- 21196900
TI  - Established and emerging therapies for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver
      with a worldwide increasing incidence. The incidence of HCC is closely related to
      the epidemiology of the risk factors which are mainly represented by chronic
      viral hepatitis B and C. Obesity and type II diabetes, often associated with
      chronic nonalcoholic fatty liver disease, are emerging independent risk factors
      for HCC development. Although the risk factors for HCC are well characterized,
      the molecular mechanisms responsible for malignant transformation of hepatocytes
      are not well understood. HCC diagnosis and therapy follow defined algorithms
      according to the European Association for the Study of the Liver and the American
      Association for the Study of Liver Diseases guidelines. Liver transplantation has
      been shown the best outcome for selected patients with early tumor stage but its
      application is limited by the shortage of liver grafts. After hepatic resection
      prognosis remains unsatisfactory due to a high incidence of tumor recurrence.
      Selective internal radiation therapy is emerging as promising loco-regional
      treatment for patients with advanced HCC having good performance status and liver
      reserve but not amenable to surgery. The recently introduced orally active
      multikinase inhibitor sorafenib has been established as palliative systemic
      therapy. Further improved understanding of molecular mechanisms underlying HCC
      development will facilitate the development of new targeted therapeutic
      strategies.

PMID- 21196901
TI  - Lyme disease diagnosis and treatment: lessons from the AIDS epidemic.
AB  - Lyme disease is a controversial tick-borne illness that is estimated to be four
      times more common than AIDS in the United States. This paper outlines the
      challenges overcome in the healthcare response to human immunodeficiency virus
      (HIV) infection, the development of sensitive laboratory tests for the AIDS
      virus, and the promotion of long-term combination antimicrobial regimens to
      effectively treat HIV disease. We suggest that similar challenges need to be
      overcome before the chronic form of Lyme disease can be successfully treated.
      Currently, diagnosis and treatment of Lyme disease is hindered by the lack of a
      uniform case definition that adequately reflects the clinical presentation of the
      disease, poor laboratory test sensitivity, and high treatment failure rates using
      short-term monotherapy. Consequently the optimal treatment for patients with
      persistent symptoms of Lyme disease remains undefined. Although antibiotic
      monotherapy has been successful in treating early Lyme disease, the use of
      combination antibiotic therapy modelled on HIV treatment appears to be more
      effective for patients with persistent symptoms of tick-borne infection.
      Resolution of the controversy surrounding Lyme disease should lead to improved
      diagnosis and treatment modelled on the approach to HIV disease.

PMID- 21196902
TI  - [Physiopathology and management of pain in multiple myeloma].
AB  - Pain is a troublesome problem in multiple myeloma (MM) patients which may be
      affected by several pain syndromes sustained by different underlying causes and
      mechanisms- In this setting may be due to the disease itself, to its
      complications, to diagnostic procedures and therapeutic interventions. Most pain
      syndromes origin from the skeleton and are related to several aspects of the
      myeloma bone disease (osteolysis and osteopenia). Other remarkable pains
      frequently observed in MM are due to disease-related and iatrogenic neuropathies.
      For most MM patients the World Health Organization's three-step analgesic ladder
      can be effective, although difficult-to-treat pain conditions are frequently
      observed, given the occurrence of some prognostically negative features, such as
      the mechanical instability and some neuropathic conditions. Therefore, the
      management of pain in this setting should require a multidisciplinary approach
      and the application of causal interventions (chemotherapy and radiotherapy) and
      of other pain-relieving procedural measures (i.e. vertebroplasty and orthopedic
      surgery). A prompt treatment of pain is necessary in order to avoid potentially
      devastating consequence, such the occurrence of chronic pain syndromes which may
      be due to central sensitization.

PMID- 21196903
TI  - Early management of hearing and balance disorders: a review of literature and a
      proposal to overcome possible uncertainties.
AB  - The lack of a correct diagnostic and therapeutic planning of vestibular diseases
      is still often observed, and some difficulties are still to deal with in clinical
      practice, even when treating acute hearing problems, although the needed
      competence is more easily identified as otologic. A review of the international
      literature confirms the existence of such a problem, and permits to underline the
      scarcity of connections between otology and neurotology, on one hand, and
      principles of basic sciences and general and internal medicine, on the other
      hand: this can explain some therapeutic contradictions in treating inner ear
      disorders, their frequent labelling as idiopathic and the persisting
      uncertainties concerning a correct diagnostic and therapeutic management. In
      order to overcome the difficulties deriving to insufficient interdisciplinary
      cooperation, the institution of hospital audiovestibular services with a strictly
      linked net of cooperation with internal medicine units could represent a
      progress. This could help prevent clinically and economically inadequate
      management, contributing to minimize the possibility of expensive and/or health
      threatening mistakes; moreover, it could represent an example to easily improve
      the practical aspects of both pre graduate and postgraduate curricula, and to
      form more open-minded clinicians, starting both from an ear. Nose and throat
      (ENT)/audiological and from an Internal Medicine extraction.

PMID- 21196904
TI  - Ethical models in bioethics: theory and application in organ allocation policies.
AB  - Policies for allocating organs to people awaiting a transplant constitute a major
      ethical challenge. First and foremost, they demand balance between the principles
      of beneficence and justice, but many other ethically relevant principles are also
      involved: autonomy, responsibility, equity, efficiency, utility, therapeutic
      outcome, medical urgency, and so forth. Various organ allocation models can be
      developed based on the hierarchical importance assigned to a given principle over
      the others, but none of the principles should be completely disregarded. An
      ethically acceptable organ allocation policy must therefore be in conformity, to
      a certain extent, with the requirements of all the principles. Many models for
      organ allocation can be derived. The utilitarian model aims to maximize benefits,
      which can be of various types on a social or individual level, such as the number
      of lives saved, prognosis, and so forth. The prioritarian model favours the
      neediest or those who suffer most. The egalitarian model privileges equity and
      justice, suggesting that all people should have an equal opportunity (casual
      allocation) or priority should be given to those who have been waiting longer.
      The personalist model focuses on each individual patient, attempting to mesh
      together all the various aspects affecting the person: therapeutic needs
      (urgency), fairness, clinical outcomes, respect for persons. In the
      individualistic model the main element is free choice and the system of opting-in
      is privileged. Contrary to the individualistic model, the communitarian model
      identities in the community the fundamental elements for the legitimacy of
      choices: therefore, the system of opting-out is privileged. This article does not
      aim at suggesting practical solutions. Rather, it furnishes to decision makers an
      overview on the possible ethical approach to this matter.

PMID- 21196905
TI  - Efficacy of clarithromycin plus metronidazole-based triple therapy for
      Helicobacter pylori eradication: a retrospective study.

PMID- 21196906
TI  - Itraconazole as a novel addition to ANCA-associated vasculitides or other
      neutrophilic dermatosis armamentarium.

PMID- 21196907
TI  - Umbilical cord morphology in pregnancies complicated by IUGR in cases of tobacco
      smoking and pregnancy-induced hypertension.
AB  - OBJECTIVE: The aim of this study was to determine the characteristic features of
      the umbilical cord morphology in selected cases of intrauterine growth
      restriction (IUGR): tobacco smoking, pregnancy-induced hypertension and
      idiopathic IUGR. MATERIALS AND METHODS: 136 pregnant women were included in the
      study - 86 patients with IUGR (IUGR group) and 50 women with uncomplicated course
      of pregnancy (control group). In the IUGR group 31 women were smokers, 27
      suffered from pregnancy-induced hypertension, and 28 had an unknown reason for
      IUGR. Each of them underwent ultrasound examination to measure fetal growth and
      to assess morphological parameters of the umbilical cord. RESULTS: Significant
      differences between the control group and the whole IUGR group in terms of the
      diameter of the umbilical cord and diameter of the umbilical vein - smaller
      diameters in the IUGR group than in the control group. Significant differences
      among IUGR subgroups in terms of area of Wharton's jelly and diameters of the
      umbilical cord, vein and artery. Significant difference in the length of the
      uncoiled section among the IUGR subgroups. CONCLUSIONS: 1. The umbilical cord in
      IUGR and concomitant tobacco smoking is hyper-coiled with coiling index
      independent of fetal weight and high content of Wharton's jelly. 2. The umbilical
      cord in IUGR and concomitant pregnancy-induced hypertension is thinnest with
      thinnest vessels and the smallest content of Wharton's jelly. 3. The assessment
      of umbilical cord morphology should become an integral part of ultrasound exam in
      pregnancies complicated by IUGR.

PMID- 21196908
TI  - Umbilical cord blood concentrations of IL-6, IL-8, and MMP-8 in pregnancy
      complicated by preterm premature rupture of the membranes and histological
      chorioamnionitis.
AB  - OBJECTIVE: To determine whether umbilical cord blood concentrations of
      interleukin-6 (IL-6), interleukin-8 (IL-8), and matrix metalloproteinase-8 (MMP
      8) are of value in the diagnosis of histological chorioamnionitis (HCA) and
      funisitis in patients with preterm premature rupture of membranes (PPROM).
      SETTING: Department of Obstetrics and Gynaecology, Charles University in Prague,
      Faculty of Medicine Hradec Kralove, University Hospital Hradec Kralove, Czech
      Republic. METHODS: We compared umbilical cord blood IL-6, IL-8, and MMP-8
      concentrations in 83 women with PPROM between 24th and 36th gestational weeks
      with the presence and the absence of HCA/funisitis using nonparametric tests
      (Mann-Whitney U test), given the non-normal distribution of analyte. Comparisons
      of proportions were performed the D'Agostino and Pearson omnibus normality test
      and the Shapiro-Wilk test. RESULTS: Patients with HCA had a significantly higher
      median umbilical cord blood IL-6 concentration than patients without histological
      signs of inflammation (12.0 pg/mL [2.1-138.3] versus 2.7 pg/mL [0.1-12.4];
      p=0.004) but did not have significantly higher median umbilical cord IL-8 (29.9
      pg/mL [14.0-186.3]; versus 18.9 pg/mL [7.9-89.4]; p=0.13) and MMP-8 (2.9 pg/mL
      [0.5-25.2] versus 0.5 ng/mL [0.5-7.9]; p=0.18). Patients with HCA and funisitis
      had a significantly higher median umbilical cord blood IL-6 (222 pg/mL [95.3
      411.7] versus 6.1 pg/mL [1.3-18.5]; p<0.0001) and IL-8 (20.9 pg/mL [8.4-37.7]
      versus 190.7 pg/mL [83.8-554.2]; p=0.0004) concentration than patients with HCA
      alone. Differences were not found in MMP-8 concentrations (3.7 ng/mL [0.5-21.4]
      versus 2.4 ng/mL [0.5-88.1]; p=0.7). CONCLUSION: HCA was associated with a
      significant increase in umbilical cord blood IL-6 concentration. In patients with
      HCA and funisitis, umbilical cord blood IL-6 and IL-8 were significantly higher
      than those without histological signs of inflammation.

PMID- 21196909
TI  - Ultrasound measurements of the transverse diameter of the fetal thymus in
      uncomplicated singleton pregnancies.
AB  - OBJECTIVE: To determine sonographically the transverse diameter of the fetal
      thymus and present nomogram for the transverse diameter of the fetal thymus in
      uncomplicated singleton pregnancies between 19 and 38 weeks of gestation.
      SETTING: Department of Obstetrics and Gynecology, Charles University in Prague,
      Faculty of Medicine Hradec Kralove, University Hospital Hradec Kralove, Czech
      Republic. METHODS: A prospective study was performed. The transverse diameter of
      the fetal thymus was measured by the one experienced examiner in 198 healthy
      fetuses between 19 and 38 weeks of gestation. RESULTS: The transverse diameters
      of the fetal thymus were obtained from 183 of the 198 subjects. The regression
      equation was expressed as a function of gestational age: the transverse diameter
      of the fetal thymus (mm) = 1.001 * gestational age (week) - 0.932 or 0.143 * day 
      1.34. Both the correlation coefficients, r=0.91 for weeks and r=0.92 for days
      were found to be highly statistically significant (p<0.0001). CONCLUSION: This
      study presents normative data (mean, 5th and 95th) for the ultrasound
      measurements of the transverse diameter of the fetal thymus in healthy singleton
      pregnancies.

PMID- 21196910
TI  - The effect of chemical sympathectomy and stress on bone remodeling in adult rats.
AB  - OBJECTIVES: Bone remodeling has recently been revealed to be under sympathetic
      nerve control. The role of the sympathetic nerve system is not clearly
      understood. The present study aim to explore the effect of chemical sympathectomy
      and stress on bone remodeling in adult rats. METHODS: 24 twelve-month-old Wistar
      rats were divided into three group (sympathectomy, stress and control). The
      sympathectomy and stress group rats were administered 6-hydroxydopamine (150
      mg/kg each day) and saline (1 ml/kg each day) intraperitoneal respectively for
      one week and exposed to stress procedure for another three weeks. The stress
      procedure was mild, unpredictable footshock, administered for one hour once
      daily. Analysis of serum chemistry, microcomputed tomography, dual energy X-ray
      absorptiometry, biomechanical testing and bone histomorphometry were employed.
      RESULTS: The stress group rats showed increased bone resorption in contrast to
      the sympathectomy and control group rats. The serum level of calcium and
      phosphorus cations and norepinephrine were enhanced, the cancellous bone volume
      and bone mineral density were reduced, bone mechanical property such as strength,
      ductility and toughness were weakened, the osteoclast counts and osteoclast
      surfaces were increased and the bone formatin rate were decreased significantly
      in the stress group rats in contrast to the other two groups rats. There was no
      significant difference of bone remodeling between the sympathectomy group and
      control group rats. CONCLUSION: Our study showed stress-increased sympathetic
      nerve system activity enhanced bone resorption while chemical sympathectomy
      inhibited bone resorption under stress. We postulate sympathetic neurotransmitter
      and neuropepitide may play a role in regulating bone remodeling.

PMID- 21196911
TI  - Subclinical hyperthyroid patients' knowledge about radioiodine therapy--the key
      role of medical information.
AB  - OBJECTIVES: Many patients with a chronic disease are dissatisfied with the
      information they are given. A brief questionnaire completed by patients would
      assist health professionals to identify areas of information needed to be
      provided, tailored to the patient's mental condition. AIM: The aim of our study
      was to assess how often thyroid patients report being adequately informed about
      iodine treatment in connection with their real need thereof, emotional state and
      acceptance of the disease. METHODS: One hundred outpatients who had presented
      subclinical hyperthyroidism "[19 men (19%), 81 women (81%); mean (SD+/-) age 53+/
      14,range 18-77 yr ] treated with radioiodine (RAI) responded to an Experimental
      Questionnaire, 54 of them answered to AIS, HADS-M and Beck Inventory measuring
      their acceptance of the illness and depressive symptoms, 37 of them answered the
      Patient Request Form (PRF). RESULTS: The obtained results indicated that about
      50% of patients treated with 131I therapy did not receive suitable information
      about their treatment. Neither written information prepared by the specialist,
      nor verbal information given by physicians were adequate for specific problems of
      study group. The examined patients presented with a comparable intensity of three
      distinct types of requests: for explanation and reassurance, for emotional
      support, and for investigation and treatment. The acceptance of their disease was
      mediocre for most of the study group. CONCLUSION: We conclude that the reported
      lack of satisfaction with medical information in study group was associated with
      depressive symptoms influencing cognitive efficiency, patients' great need of
      emotional and cognitive support, influencing the acceptance of their disease, and
      social prejudice to radioiodine (as a method of treatment), worrying them
      additionally. All thyroid patients even these with subclinical symptoms of
      hyperthyroidism should be treated with specific attention by physicians,
      especially during information process.

PMID- 21196912
TI  - Salivary testosterone levels and autism-spectrum quotient in adults.
AB  - OBJECTIVES: The purpose of this study is to examine the relationship between
      salivary testosterone levels and autistic traits in adults. METHODS: A total of
      92 male and female adults participated in the present study. Their salivary
      testosterone level (T) and score of Japanese version of Autism-spectrum Quotient
      (AQ) were assessed to examine the relationship between salivary testosterone
      level and autistic traits in adults. RESULTS: We observed a positive correlation
      between T and AQ in a group of both sexes. The correlation disappeared when we
      conducted correlation analysis by sex. However, although there was no sex
      difference in the score of the subscale of attention switching, attention
      switching was related to T. CONCLUSIONS: Although the relationship between T and
      AQ may mainly result from sex differences, the subscale of attention switching
      may be modulated by testosterone.

PMID- 21196913
TI  - Salivary alpha-amylase levels and big five personality factors in adults.
AB  - OBJECTIVES: Salivary alpha-amylase (sAA) has been utilized as a non-invasive
      measure of sympathoadrenal medullary (SAM) activation. Little is known regarding
      the relationship between personality inventories and baseline sAA. This study was
      designed to examine the relationships between the scores of big five inventory
      (BFI) factors, age, and sAA in adults (aged twenty to seventy years old).
      METHODS: We assessed 97 participants' BFI scores and sAA. The correlations
      between the BFI factor scores and sAA were examined. RESULTS: We observed (1) a
      positive correlation between Neuroticism and sAA, and a negative correlation
      between Agreeableness and sAA and (2) a positive correlation between age and sAA.
      These correlations between BFI scores and sAA remained significant after
      controlling for age. After controlling for age, all BFI factors except
      Conscientiousness were related to sAA. CONCLUSIONS: Subjects with high
      Neuroticism and low Extraversion, Agreeableness and Openness may have high sAA.
      sAA has been demonstrated to be useful for examining the relationship between
      adrenergic activity and personality, in a non-invasive manner.

PMID- 21196914
TI  - Roles of dopamine receptor subtypes in mediating modulation of T lymphocyte
      function.
AB  - OBJECTIVE: Dopamine exists in the immune system and has obvious immunomodulating
      action. However, receptor mechanism underlying the dopamine immunomodulation
      remains to be clarified. In the present study, we provide the evidence for
      existence of dopamine receptor subtypes in T lymphocytes and show the roles of
      the receptors and the receptor-coupled signaling in mediating the dopamine
      immunomodulation. METHODS: The purified T lymphocytes from the mesenteric lymph
      nodes of mice were detected for expressions of all five subtypes of dopamine
      receptor mRNAs by reverse transcription-polymerase chain reaction. Lymphocyte
      proliferation and production of interferon-gamma (IFN-gamma) and interleukin-4
      (IL-4) in response to concanavalin A (Con A) were measured by colorimetric methyl
      thiazole-tetrazolium assay and cytometric bead array, respectively, after the
      cells were exposed to dopamine D1-like or D2-like receptor agonists and
      antagonists. Meanwhile, content of cAMP and phosphorylation of cAMP-response
      element-binding (CREB) in the lymphocytes were examined by 125I-cAMP
      radioimmunoassay and Western blot assay, respectively. RESULTS: T lymphocytes
      expressed all the five subtypes of dopamine receptor mRNAs, i.e., D1, D2, D3, D4
      and D5 receptors. SKF38393, an agonist of dopamine D1-like receptors (D1 and D5
      receptors) only reduced the IFN-gamma production, but did not significantly
      affect the proliferative response, IL-4 production, cAMP content or CREB
      activation of the lymphocytes. The SKF38393-induced decrease in IFN-gamma level
      was blocked by the D1-like receptor antagonist SCH23390. Quinpirole, an agonist
      of dopamine D2-like receptors (D2, D3 and D4 receptors) attenuated the lymphocyte
      proliferation to Con A, and decreased the IFN-gamma but increased the IL-4
      production. Meanwhile, the quinpirole diminished the cAMP content and the
      phosphorylated CREB level in the lymphocytes. All the quinpirole-induced changes
      were reversed by dopamine D2-like receptor antagonist haloperidol. CONCLUSIONS:
      Five dopamine receptor subtypes of the two families, D1-like and D2-like
      receptors, exist on T lymphocytes of mice. Of the two families, D2-like receptors
      are more important in mediating modulation of T cell function than D1-like
      receptors. D2-like receptors are involved in suppression of T helper 1 (Th1) cell
      function and enhancement of Th2 cell function through negative link to cAMP-CREB
      pathway.

PMID- 21196915
TI  - Pineal ribbon synapses: regulated by the gland's central innervation.
AB  - OBJECTIVE: The pineal gland is part of the circadian clock system and is under
      the predominant influence of the endogenous oscillator located in the
      suprachiasmatic nucleus. A polysynaptic pathway involving hypothalamus, spinal
      cord and sympathetic system regulates the so far best-studied aspect of its
      neuroendocrine output, i.e., the synthesis and secretion of melatonin. This
      parameter increases dramatically at night upon sympathetic activation in rats and
      many other mammals including man. In addition, parasympathetic, trigeminal,
      diencephalic and other sites or mechanisms connect the gland, mainly via its
      stalk, to the nervous system. However, their function for pineal metabolic or
      morphological features are hardly known. An interesting ultrastructural attribute
      of the pineal gland are ribbon synapses. These presynaptic structures in
      pinealocytes are composed of a ribbon and vesicles. They are thought to regulate
      and facilitate multivesicular release, and display a circadian rhythm with higher
      levels at night paralleling melatonin synthesis but regulated differently.
      METHODS: To gain more insight into the roles of both, the non-sympathetic
      ("central") innervation and the regulation of pineal ribbon synapses, a surgical
      transection of the pineal stalk was conducted in rats and the number of synaptic
      ribbons (SR) were determined by electron microscopy from experimental, sham
      operated and control animals. RESULTS: The transection resulted in normal daytime
      levels but diminished the nocturnal increase of SR numbers when compared to
      controls or sham-operated rats. CONCLUSION: These data provide first evidence
      that the central innervation of this neuroendocrine organ plays an important role
      in SR (up)regulation, and that this pathway is antagonistic to the sympathetic
      innervation.

PMID- 21196916
TI  - Phase shift of the circannual reproductive rhythm in European hamsters by 2 days
      of long photoperiod.
AB  - OBJECTIVES AND DESIGN: In European hamsters a circannual clock drives the
      seasonal changes in the reproductive state. Its resetting by photoperiod is
      clearly phase dependent. In mid subjective winter a 1-month pulse of long
      photoperiod (LP) advances the onset of the reproductive phase of animals
      maintained in constant short photoperiod (SP) by up to 1.5 months. The present
      study investigated whether shorter pulses, i.e. 8, 4 or 2 days LP-pulses are
      still effective to phase shift the circannual rhythm. MAIN FINDINGS: All pulses
      induced gonadal development after a similar time relative to the offset of the
      pulse and earlier than in the control group. Thus, they all shared a similar
      effectiveness. CONCLUSIONS: In European hamsters a very brief LP-pulse can phase
      shift the reproductive rhythm but its strength is not determined by its duration
      at least not in the tested range.

PMID- 21196917
TI  - Nicotine effects on rat seizures susceptibility and hippocampal neuronal
      degeneration.
AB  - OBJECTIVES: Nicotine is a widely used drug of abuse exerting number of effects on
      the central nervous system. The study was aimed at the effects of nicotine in
      various doses on the excitability of cerebral cortex and - by using the methods
      of histochemistry - to identify possible signs of neuronal degeneration after
      nicotine administration. METHODS: Cortical afterdischarges were elicited by
      repeated stimulation of the right sensorimotor cortex. The duration of evoked ADs
      was monitored in animals treated with nicotine (0.75 or 1.0mg/kg) and in animals
      treated with saline. Methods of histochemistry (Fluoro-Jade B and bis-benzimide)
      were used to detect possible neuronal degeneration in hippocampus or in cerebral
      cortex. RESULTS: No Fluoro-Jade B positive cells were found in hippocampi of
      control animals, or animals treated with nicotine. ADs length was significantly
      influenced by administration of nicotine. CONCLUSION: Nicotine in 0.75 or 1.0
      mg/kg dose leads to the decrease in ADs duration, influences the seizure
      susceptibility, and doesn't cause any detectable neuronal damage.

PMID- 21196918
TI  - Neuronal expression of inducible nitric oxide synthase in hypothyroid rat.
AB  - OBJECTIVES: The expression of iNOS mRNA and protein levels was studied in
      hypothyroid rat cerebral cortex during early days after postnatal life. METHOD:
      The homogenate of the cerebral cortex was examined using Real-time reverse
      transcription polymerase chain reaction (real-time RT PCR) and Western blot
      analysis. RESULT: DeltaCt in hypothyroid group on day 7, 14, 21 was 18.89+/-0.92,
      18.83+/-0.99, 16.48+/-0.29, separately. While in control group, DeltaCt was
      20.32+/-0.92, 20.07+/-0.86, 17.96+/-0.50, separately. Meanwhile, the protein
      level was detected only in hypothyroid group of 59 +/- 5% on day 14. On day 21,
      iNOS protein expression showed a decrease (p<0.05) in hypothyroid group (37 +/-
      3%), compared with control group (58 +/- 4%). CONCLUSION: Our findings show the
      successive changes of the iNOS mRNA and protein levels in early postnatal days of
      hypothyroid rat brain, and confirm the cross-talk between the TH and NO signaling
      pathway in developing cerebral cortex of rats.

PMID- 21196919
TI  - Posterior reversible encephalopathy syndrome associated with nephrotic syndrome.
AB  - Kabicek and colleagues described a case of nephritic-syndrome-associated
      posterior reversible encephalopathy syndrome (PRES) (Kabicek, et al. 2010). This
      adds to the accumulating evidence that PRES can be associated with disorders
      other than hypertension. However, we wonder how the authors would explain the
      neuroimaging findings unsuggestive of vasogenic oedema. PRES (also named
      reversible posterior leukoencephalopathy syndrome, RPLS) represents a
      clinicoradiological syndrome characterized by vasogenic oedema as revealed by
      apparent diffusion coefficient (ADC) map of diffusion-weighted imaging (DWI)
      (Bartynski, 2008). The pathogenesis of PRES has been suggested to be
      autoregulation failure and endothelial dysfunction (Sharma, et al.). ...

PMID- 21196921
TI  - Is pseudo-intractability in population of patients with epilepsy still alive in
      the 21st century? Audit of 100 seizure-free patients, referred with the diagnosis
      of pharmacoresistant epilepsy.
AB  - OBJECTIVE: There is no universally accepted definition of pseudo-intractable
      epilepsy. Pseudo-intractability means that the resistance to treatment is, in
      fact, caused by clinical errors. The purpose of our study was to identify the
      reasons for intractability and subsequent effective therapeutic management
      approaches in a group of patients with established pseudo-intractable epilepsy.
      METHODS: The study was designed as a retrospective audit of 100 adult patients
      who, in their past medical history, were diagnosed as having intractable epilepsy
      but, following adjustments to their medical management, were seizure free for at
      least 2 years. Patients underwent standard clinical evaluation, including EEG
      and/or video-EEG monitoring. We re-evaluated past medical, family, seizure and
      pharmacological history and morphological findings. Epilepsy was re-classified
      according to the ILAE classification. RESULTS: We identified possible errors
      including incorrect diagnosis and/or inappropriate previous epilepsy management
      in all 100 patients. Incorrect diagnosis (seizure type and/or syndrome) was
      observed in 47 patients (47%). Thirty two patients (32%) with idiopathic
      generalized epilepsy were treated for complex focal seizures with inappropriate
      choice of medication. Therapeutic errors were identified in 48 patients (48%).
      Issues with medication compliance were found in 20 patients (20%). Potential
      seizure precipitating factors were detected in 23 patients (23%). CONCLUSIONS:
      Our study of 100 patients confirmed that the problem of pseudo-intractability
      still exists. Every case of pharmacoresistance in epilepsy could potentially be
      caused by one or more clinical errors.

PMID- 21196922
TI  - Individualized treatment of eating disorders.
AB  - OBJECTIVE: The goal of this study is to determine how a comprehensive approach
      comprising a combination of a particular psychotherapeutic programme and
      antidepressant treatment influences the signs and symptoms of eating disorders.
      METHODS: Inpatients entering a particular 6-week programme were assessed using
      body mass index (BMI), Eating Disorder Inventory (EDI), Eating Attitudes Test
      (EAT-26) and psychological symptoms using Symptom Checklist (SCL-90). RESULTS: In
      the whole group (n=84) the mean BMI remained stable (17.9, 17.8). There was a
      significant effect of TIME in the repeated measures ANOVA with most of dependent
      variables. The "TREATMENT" had no effect (antidepressants, no antidepressants)
      and there was no significant interaction between "TREATMENT" and "TIME". Post-hoc
      analysis revealed significant differences between baseline and end-point values
      of all but two EDI, all EAT items and some SCL dimensions in the antidepressant
      treated group. CONCLUSIONS: The comprehensive and individualized approach is able
      to achieve weight stabilization, and improvement in attitudes, pathological
      eating behaviour and psychopathology.

PMID- 21196923
TI  - Increased fractional anisotropy in white matter of the right frontal region in
      children with attention-deficit/hyperactivity disorder: a diffusion tensor
      imaging study.
AB  - Abnormalities of frontal white matter (WM) have been found in some children with
      ADHD. The purpose of this study was to explore the changes in WM in child
      patients with ADHD by DTI, which detects changes in WM microstructure based on
      properties of diffusion. We also expect to investigate the relationship between
      the changes in WM and executive function in child patients with ADHD. DTI was
      performed on 24 patients with ADHD and 20 healthy controls. A series of
      neuropsychological tests and a structural interview were conducted to assess the
      cognitive functions and clinical data of the ADHD patients and controls. Firstly,
      child patients with ADHD have higher fractional anisotropy (FA) values in WM in
      the right frontal region. Secondly, FA in right frontal WM is positively
      correlated with scores in the Stroop test. CONCLUSIONS: Increased FA of right
      frontal WM implies a higher degree of myelination and lower degree of neural
      branching in WM, contributing to the neurological deficits of ADHD.

PMID- 21196924
TI  - How to have an effective academic sabbatical: recommendations for what to do and
      what to avoid.
AB  - Sabbaticals - i.e., academic sabbaticals, sabbatical leaves, sabbatical semesters
      - provide faculty members with a unique opportunity to engage in scholarly
      projects. Ranging from a year to shorter periods, these time windows - usually
      free of rigid day-to-day obligations - can be powerful means to reflect on past
      and present projects, to renew perspectives, and to receive fresh impetus for
      both your research and teaching. When reading the literature on sabbaticals, it
      is somewhat surprising that relatively small amounts of space are devoted to this
      important part of academic life. Here we provide practical recommendations [1-4:
      pre-sabbatical; 5-8: intra-sabbatical; 9-10: post-sabbatical] for making your
      sabbatical a satisfying endeavor.

PMID- 21196925
TI  - Growth hormone-releasing hormone stimulates the secretion of interleukin 17 from
      human peripheral blood mononuclear cells in vitro.
AB  - OBJECTIVES: Growth hormone-releasing hormone (GHRH) plays a crucial role in the
      secretion of GH from the pituitary, acts as a growth factor in variety of cancer
      cells and possesses immunomodulatory activity. Interleukin(IL)-17 apart from its
      pro-inflammatory role has been also shown to play a role in carcinogenesis. The
      effect of GHRH on the IL-17 has not been studied so far. AIM: To evaluate the
      effect of GHRH on the secretion of IL-17 from human peripheral blood mononuclear
      cells (PBMC) in vitro. MATERIALS AND METHODS: The concentrations of IL-17 in
      supernatants from PBMC cultured for 24 hrs were assessed using ELISA kit.
      RESULTS: We show for the first time that GHRH can stimulate the secretion of IL
      17 from human PBMC in 24 hrs culture, and that GHRH antagonist counteracts this
      effect. CONCLUSION: Our study further elucidates the immunomodulatory role of
      GHRH.

PMID- 21196926
TI  - Expression of Ki-67, p53 and vascular endothelial growth factor (VEGF)
      concomitantly in growth hormone-secreting pituitary adenomas; which one has a
      role in tumor behavior ?
AB  - OBJECTIVE: In many pituitary tumor, immunohistochemical studies have been shown
      to be correlated with different aspects of tumor behavior.There is no study up to
      date in which markers of Ki-67, p53, VEGF were evaluated concomitantly in GH
      secreting adenomas.This study aims to determine which marker has a major role in
      tumor behavior and whether these markers have a cut-off value to distinguish
      invasive adenoma from non-invasive pituitary adenoma. METHODS: Fourty-seven
      acromegalic patients operated by the same neurosurgeon were included in this
      study.Twenty-one patients(5micro/16 macro) had non-invasive adenomas and 26 had
      invasive macroadenomas.Eight patients(6 invasive macroadenomas, 2 microadenomas)
      were treated with OCT-LAR until one month prior to surgery with treatment
      duration range of 3-11 months.These patients were excluded from the study group
      as the noninvasive and invasive adenomas were compared.A separate analysis was
      performed in invasive adenomas to compare OCT(+) and OCT(-)patients. RESULTS:
      Both Ki-67 and p53 expressions showed no correlation with the invasive character
      of adenomas, but VEGF expression in invasive adenomas was significantly higher
      with respect to noninvasive group.Our study has taken intermediate staining (>25
      %)for VEGF as a cut off value for invasive adenomas.It was also observed that the
      decrease in VEGF staining in OCT pretreated invasive adenomas was significantly
      more than those not treated with OCT. CONCLUSION: VEGF becomes an independent
      stimulator of angiogenic growth and progression for GH-secreting adenomas with
      >25% cytoplasmic immunoreactivity.This cut-off value may be useful in
      determination of prognosis and appropriate treatment strategy.A short term
      preoperative OCT treatment may be useful as adjunctive therapy especially for
      locally invasive GH- secreting adenomas.

PMID- 21196927
TI  - Elevated immunoglobulin D levels in children with PFAPA syndrome.
AB  - BACKGROUND: The periodic fever, aphthous stomatitis, pharyngitis and cervical
      adenitis (PFAPA) syndrome appears to be more common than generally appreciated
      and should be differentiated from hereditary periodic fever syndromes,
      particularly from mevalonate kinase deficiency (MKD). PATIENTS AND METHODS: 14
      unrelated patients (7 males, 7 females) met clinical criteria for both the PFAPA
      syndrome and MKD. Immunoglobulin D (IgD) levels, mevalonic aciduria and
      mevalonate kinase (MVK) genotype was determined in all patients. RESULTS:
      Children experienced their first febrile episode at the age of 24.5+/-5.9 months
      (mean+/-SD), the clinical diagnosis of PFAPA syndrome was established with delay
      at 42.7+/-11.7 months. The duration of febrile episodes was 3.4+/-0.2 days, the
      asymptomatic interval between them lasted 5.4+/-0.9 weeks. Accompanying symptoms
      included pharyngitis (92.8%), cervical lymphadenitis (85.7%), aphthous stomatitis
      (21.4%), arthralgia (14.3%) and skin erythema (35.7%). Neither mevalonic aciduria
      nor MVK gene mutations were found in any of the subjects, however, unexpectedly,
      increased plasma IgD (322.2+/-29.2 U/l) levels were detected in all patients.
      CONCLUSION: Raised IgD levels may represent a non-specific epiphenomenon, which
      frequently accompanies PFAPA syndrome as well as MKD. Because of the overlapping
      clinical and laboratory features, genetic testing of the MVK gene is indicated to
      differentiate these two conditions, if clinical criteria for both are fulfilled.

PMID- 21196928
TI  - Difficulties in diagnosis of solitary and sporadic epileptic seizures.
AB  - OBJECTIVE: Authors warn of difficulties in diagnostic of solitary epileptic
      seizure and epilepsy. MATERIAL AND METHODS: Our groups have been made up of
      patients, who have been dismissed from our clinic in the period from January 1997
      to January 2007 with diagnosis of solitary unprovoked epileptic seizure (n=84)
      and epilepsy with sporadic epileptic seizure (n=179). We have evaluated the
      clinical typology of epileptic seizure, EEG findings and results of imaging
      methods and we determined the part of patients with complete diagnostic
      concordance between clinical image of epileptic seizure and results of auxiliary
      diagnostic methods. RESULTS: We have denoted the complete diagnostic concordance
      among the clinical image, EEG findings and results of imaging methods only in
      13.1% of patients after solitary unprovoked epileptic seizure and in 24.02% of
      patients with diagnosis of epilepsy with sporadic epileptic seizures. The
      receiving diagnosis of unclear seizure status was determined at 49.14% of
      patients dismissed with diagnosis of solitary epileptic seizure and at 40.78% of
      patients dismissed with diagnosis of epilepsy with sporadic epileptic seizures in
      10 year time period. CONCLUSION: Our results repeat the confirmation that the
      diagnostic of seizure disorders, with and without disturbance of consciousness,
      belong to the difficult part in the clinical praxis.

PMID- 21196929
TI  - Glycemic control improvement through treatment of depression using antidepressant
      drugs in patients with diabetes mellitus type 1.
AB  - OBJECTIVE: Depression is a common disorder among diabetic patients and affects
      negatively the treatment of their basic disease. The aim of the study was to
      assess, whether antidepressant medication could positively influence glycemic
      control of diabetes type 1 in depressive or anxious patients. METHODS: A six
      month, double-blinded, randomized, placebo-controlled study was performed to
      investigate the reaction of type 1diabetic patients (n=21) to treatment of
      depression and anxiety symptoms using antidepressant drug sertraline. The
      patients were given sertraline (100 mg/day) or placebo. The evolution of mental
      change was assessed using Zung Self-Rating Depression Scale (SDS), Hamilton
      Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD) along
      with development of somatic parameters commonly assessed in diabetic patients,
      especially glycosylated hemoglobin, insulin dose and body weight. The level of
      active substance in serum of the patients was also measured. RESULTS: Mental
      state improved at the level of statistical significance of p<0.001 in both
      patients using antidepressant and placebo. From somatic parameters, body weight
      and systolic blood pressure increased statistically significantly also in both
      groups of patients. CONCLUSIONS: The mental state of most patients who
      successfully completed the study improved regardless of the fact if they were
      using antidepressant or placebo. No statistically significant connections between
      the mental and somatic changes were found. This finding points out to the placebo
      effect of the medication, to the importance of a contact with patients, but also
      to the need to concentrate on their mental state.

PMID- 21196930
TI  - Central and peripheral correlates of eye movements in selected mood disorders.
AB  - OBJECTIVES: Abnormalities and disturbances of saccadic and pursuit eye movements
      were studied in several mental disorders and diseases. Certain irregularities in
      the particular oculomotor behaviour have been proposed they may correspond with
      specific type of mental disorder. It was our aim to contribute to this question
      by analyzing the bioelectrical correlates of the visual-oculomotor integration in
      patients suffering from panic disorder and from depressive symptoms. METHODS: The
      horizontal saccadic eye movements, optokinetic nystagmus, saccadic eye movement
      evoked potentials as well as saccadic eye movement related potentials we recorded
      in the groups of outpatients suffering from depressive symptoms and panic
      disorder respectively. Groups of healthy volunteers served as control. RESULTS:
      Saccadic eye movements were found to be significantly more inaccurate as compared
      to healthy subjects. The gain of the optokinetic nystagmus at middle and high
      velocities was significantly lower in panic patients. Preparation of motor plan
      for a saccade as well as the time of the maximal recruitment of the oculomotor
      muscle units was delayed in both groups of patients and their oculomotor event
      related potentials were of the overall longer duration and higher variability as
      well. CONCLUSION: The changes in oculomotor behavior as well as in its EEG
      correlates in the groups of above mentioned patients can not be taken as specific
      for the given disorder. On the other hand, they may help to follow up the course
      of the complex therapy.

PMID- 21196931
TI  - Autonomic nervous system in euthymic patients with bipolar affective disorder.
AB  - BACKGROUND: Autonomic nervous system (ANS) dysfunction and reduced heart rate
      variability (HRV) have been reported in a wide variety of psychiatric disorders,
      but have not been well characterized in bipolar patients in remission. We
      recorded cardiac activity and assessed HRV in bipolar outpatients in remission.
      AIMS: Ascertain if ANS decrease with the age of the patient; ascertain relation
      between activity of ANS and level of dissociation, and other components (age of
      patients, and age of disorder, dosage of psychotropic medication) METHODS:
      Autonomic nervous system (ANS) has been evaluated during orthostatic change in
      three positions (1 - lie down 5 minutes, 2 - stand up 5 minutes, 3 - lie down 5
      minutes). The functioning of the ANS has been measured by the diagnostic systems
      that are using the power spectral analysis which quantifies the heart rate
      variability (HRV) was assessed using time domain, frequency domain, and nonlinear
      analyses in 23 bipolar patients in remission. RESULTS: We found highly
      statistically significant negative correlations between level of dissociation
      measured by DES (Dissociative Experience Scale) and most of parameters of ANS. We
      found negative correlations between the age of the patient and activity of ANS,
      and negative correlations between activity of ANS and duration and onset of
      disorder. CONCLUSIONS: Autonomic dysregulation is associated with bipolar
      disorder in remission and has relation to level of dissociation and probably to
      age of patients and age of onset and duration of disorder.

PMID- 21196932
TI  - Ependymal cells of chordate larvae are stem-like cells that form the adult
      nervous system.
AB  - In ascidian tunicates, the metamorphic transition from larva to adult is
      accompanied by dynamic changes in the body plan. For instance, the central
      nervous system (CNS) is subjected to extensive rearrangement because its
      regulating larval organs are lost and new adult organs are created. To understand
      how the adult CNS is reconstructed, we traced the fate of larval CNS cells during
      ascidian metamorphosis by using transgenic animals and imaging technologies with
      photoconvertible fluorescent proteins. Here we show that most parts of the
      ascidian larval CNS, except for the tail nerve cord, are maintained during
      metamorphosis and recruited to form the adult CNS. We also show that most of the
      larval neurons disappear and only a subset of cholinergic motor neurons and
      glutamatergic neurons are retained. Finally, we demonstrate that ependymal cells
      of the larval CNS contribute to the construction of the adult CNS and that some
      differentiate into neurons in the adult CNS. An unexpected role of ependymal
      cells highlighted by this study is that they serve as neural stem-like cells to
      reconstruct the adult nervous network during chordate metamorphosis.
      Consequently, the plasticity of non-neuronal ependymal cells and neuronal cells
      in chordates should be re-examined by future studies.

PMID- 21196933
TI  - c-Jun N-terminal phosphorylation antagonises recruitment of the Mbd3/NuRD
      repressor complex.
AB  - AP-1 (activator protein 1) activity is strongly induced in response to numerous
      signals, including growth factors, cytokines and extracellular stresses. The
      proto-oncoprotein c-Jun belongs to the AP-1 group of transcription factors and it
      is a crucial regulator of intestinal progenitor proliferation and tumorigenesis.
      An important mechanism of AP-1 stimulation is phosphorylation of c-Jun by the Jun
      amino-terminal kinases (JNKs). N-terminal phosphorylation of the c-Jun
      transactivation domain increases target gene transcription, but a molecular
      explanation was elusive. Here we show that unphosphorylated, but not N-terminally
      phosphorylated c-Jun, interacts with Mbd3 and thereby recruits the nucleosome
      remodelling and histone deacetylation (NuRD) repressor complex. Mbd3 depletion in
      colon cancer cells increased histone acetylation at AP-1-dependent promoters,
      which resulted in increased target gene expression. The intestinal stem cell
      marker lgr5 was identified as a novel target gene controlled by c-Jun/Mbd3. Gut
      specific conditional deletion of mbd3 (mbd3(DeltaG/DeltaG) mice) stimulated c-Jun
      activity and increased progenitor cell proliferation. In response to
      inflammation, mdb3 deficiency resulted in colonic hyperproliferation and
      mbd3(DeltaG/DeltaG) mice showed markedly increased susceptibility to colitis
      induced tumorigenesis. Notably, concomitant inactivation of a single allele of c
      jun reverted physiological and pathological hyperproliferation, as well as the
      increased tumorigenesis in mbd3(DeltaG/DeltaG) mice. Thus the transactivation
      domain of c-Jun recruits Mbd3/NuRD to AP-1 target genes to mediate gene
      repression, and this repression is relieved by JNK-mediated c-Jun N-terminal
      phosphorylation.

PMID- 21196934
TI  - Hydrostatic pressure and the actomyosin cortex drive mitotic cell rounding.
AB  - During mitosis, adherent animal cells undergo a drastic shape change, from
      essentially flat to round. Mitotic cell rounding is thought to facilitate
      organization within the mitotic cell and be necessary for the geometric
      requirements of division. However, the forces that drive this shape change remain
      poorly understood in the presence of external impediments, such as a tissue
      environment. Here we use cantilevers to track cell rounding force and volume. We
      show that cells have an outward rounding force, which increases as cells enter
      mitosis. We find that this mitotic rounding force depends both on the actomyosin
      cytoskeleton and the cells' ability to regulate osmolarity. The rounding force
      itself is generated by an osmotic pressure. However, the actomyosin cortex is
      required to maintain this rounding force against external impediments.
      Instantaneous disruption of the actomyosin cortex leads to volume increase, and
      stimulation of actomyosin contraction leads to volume decrease. These results
      show that in cells, osmotic pressure is balanced by inwardly directed actomyosin
      cortex contraction. Thus, by locally modulating actomyosin-cortex-dependent
      surface tension and globally regulating osmotic pressure, cells can control their
      volume, shape and mechanical properties.

PMID- 21196935
TI  - Sublancin is not a lantibiotic but an S-linked glycopeptide.
AB  - Sublancin is shown to be an S-linked glycopeptide containing a glucose attached
      to a cysteine residue, establishing a new post-translational modification. The
      activity of the S-glycosyl transferase was reconstituted in vitro, and the enzyme
      is shown to have relaxed substrate specificity, allowing the preparation of
      analogs of sublancin. Glycosylation is essential for its antimicrobial activity.

PMID- 21196936
TI  - Histone H2B ubiquitylation disrupts local and higher-order chromatin compaction.
AB  - Regulation of chromatin structure involves histone posttranslational
      modifications that can modulate intrinsic properties of the chromatin fiber to
      change the chromatin state. We used chemically defined nucleosome arrays to
      demonstrate that H2B ubiquitylation (uH2B), a modification associated with
      transcription, interferes with chromatin compaction and leads to an open and
      biochemically accessible fiber conformation. Notably, these effects were specific
      for ubiquitin, as compaction of chromatin modified with a similar ubiquitin-sized
      protein, Hub1, was only weakly affected. Applying a fluorescence-based method, we
      found that uH2B acts through a mechanism distinct from H4 tail acetylation, a
      modification known to disrupt chromatin folding. Finally, incorporation of both
      uH2B and acetylated H4 resulted in synergistic inhibition of higher-order
      chromatin structure formation, possibly a result of their distinct modes of
      action.

PMID- 21196938
TI  - A special issue on NF-kappaB signaling and function.

PMID- 21196937
TI  - Site-resolved measurement of water-protein interactions by solution NMR.
AB  - The interactions of biological macromolecules with water are fundamental to their
      structure, dynamics and function. Historically, characterization of the location
      and residence times of hydration waters of proteins in solution has been quite
      difficult. Confining proteins within the nanoscale interior of a reverse micelle
      slows water dynamics, allowing global protein-water interactions to be detected
      using nuclear magnetic resonance techniques. Complications that normally arise
      from hydrogen exchange and long-range dipolar coupling are overcome by the nature
      of the reverse micelle medium. Characterization of the hydration of ubiquitin
      demonstrates that encapsulation within a reverse micelle allows detection of
      dozens of hydration waters. Comparison of nuclear Overhauser effects obtained in
      the laboratory and rotating frames indicate a considerable range of hydration
      water dynamics is present on the protein surface. In addition, an unprecedented
      clustering of different hydration-dynamics classes of sites is evident.

PMID- 21196939
TI  - A role for dihydrotestosterone treatment in older men?

PMID- 21196940
TI  - Analysis of the methylation pattern of six gene promoters in sperm of men with
      abnormal protamination.
AB  - It has recently been shown that alteration of the methylation pattern of
      imprinted genes is associated with different types of male infertility. The
      objective of our study was to investigate the methylation pattern of selected
      gene promoters in sperm of patients with abnormal protamine replacement. The
      promoters of OCT4, SOX2, NANOG, HOXC11, miR-17 and CREM were analyzed using
      bisulfite sequencing and the percentage of DNA methylation was compared between
      patients with an abnormal protamine 1/protamine 2 (P1/P2) ratio and
      normozoospermic controls. No significant quantitative differences were found
      between groups of patients with either an abnormally high or low P1/P2 ratio
      compared to normal controls. However, two individual samples from infertile
      subjects (2/20, 10%) showed an altered methylation pattern for the CREM gene
      promoter that was not found in control samples. These two samples had a
      significantly higher (P<0.05) promoter methylation (5.58 and 4.23%, respectively)
      compared to the control group (0.46%). In conclusion, in our pilot study, extreme
      methylations defects were not seen broadly in severely infertile men. However,
      two patients exhibited altered methylation of the CREM gene, which may be either
      causative or a result of abnormal protmaine replacement.

PMID- 21196941
TI  - Effect of matrix metalloproteinases inhibition on the proliferation and
      differentiation of HUCB-NSCs cultured in the presence of adhesive substrates.
AB  - Cell adhesion to extracellular matrix (ECM) generates intracellular signals that
      modulate cell survival, proliferation, migration and differentiation. Because of
      its heterogeneous nature, ECM has the potential to induce unique responses that
      are composition-dependent. One approach to study the effect of ECM signals on
      cell development, independently on signals from other extracellular sources, has
      been to deprive cells of serum and to analyze the influence of specific ligands.
      In the current work we determine the potential of different ECM proteins
      (fibronectin, laminin, collagen) on the proliferation and differentiation of
      human umbilical cord blood-derived neural stem cells (HUCB-NSCs) cultured in
      serum-free conditions. The effect of tested ECM components on the above processes
      might be associated with the particular pattern of their proteolysis. In this
      context enzymes that are responsible for the modification of ECM proteins are of
      particular pertinence. Matrix metalloproteinases (MMPs) represent a family of
      enzymes known to play role in the modification of ECM and by this can change the
      cell-ECM substrate interaction, required for cell development. In an effort to
      elucidate the participation of MMPs in the proliferation and differentiation HUCB
      NSCs were cultured in the presence or absence of MMPs inhibitors - GM6001 and
      doxycycline. Our results show that addition of the above inhibitors interfered
      with both the proliferation and differentiation of progenitor cells toward the
      neuronal lineage. This effect depends on the adhesive ECM substrate and is most
      pronounced in the presence of fibronectin and laminin. In conclusion, our results
      suggest that MMPs modulate interaction between HUCB-NSCs and their environment
      and therefore might be an important component in neurogenesis-associated
      processes.

PMID- 21196942
TI  - Transplantation of neural stem cells derived from human cord blood to the brain
      of adult and neonatal rats.
AB  - Searching for a reliable source of alternative neural stem cells for experimental
      treatment of neurological disorders we have established neural stem cell line
      derived from human umbilical cord blood (HUCB-NSC) (Buzanska et al. 2006). These
      cells have been shown to differentiate along neuronal and glial lineages in the
      promoting in vitro conditions. In the current study we transplanted HUCB-NSC into
      rat brain to determine whether the neural progenitors would be able to survive,
      migrate and eventually adopt neural phenotypes after exposure to central nervous
      system (CNS) microenvironment. Our experiments revealed that HUCB-NSC grafting
      into the brain of adult rats limited their survival up-to two weeks probably due
      to their elimination by severe immunological host reaction evoked by
      xenotransplantation. HUCB-NSC graft in neonates survived longer time in rat
      brain, migrated, proliferated and differentiated into neuronal cells however
      their presence in the host tissue did not exceed more than five weeks after
      transplantation.

PMID- 21196943
TI  - Hypoxia and high glucose activate tetrodotoxin-resistant Na(+) currents through
      PKA and PKC.
AB  - Voltage-gated sodium channels are critical for the initiation and propagation of
      action potentials and for the regulation of neuronal excitability. Hyperglycemia
      and hypoxia are two main changes in diabetes frequently associated with several
      complications. Although many studies on streptozotocin-induced diabetic rats
      indicate that early diabetic neuropathy is associated with increased amplitude
      and faster kinetics of sodium channels, the distinctive roles of high glucose and
      hypoxia have not been completely clarified. Here we show that hypoxic and high
      glucose conditions (overnight exposure) increase activation and inactivation of
      TTX-RINa in DRG neurons without affecting the level of expression. Hypoxia and
      high glucose alone were potent enough to induce similar or even greater
      sensitization than when both conditions were present, without any of them having
      a predominant effect. PKA is mainly responsible of the one condition effect,
      while under both hypoxia and high glucose PKC was also contributing to alter the
      kinetics, although not in a cumulative manner. These data indicate that TTX-RINa
      is significantly modulated under short-time exposure to hypoxia and high glucose,
      a mechanism which might be relevant for diabetes-related complications or other
      diseases associated with acute hypoxia.

PMID- 21196944
TI  - Cell proliferation and total granule cell number in dentate gyrus of transgenic
      Tg2576 mouse.
AB  - This report provides in vivo evidence of adult neurogenesis and the total granule
      cell count in the dentate gyrus of the Tg2576 mouse model of Alzheimer's disease.
      Mice were deeply anaesthetized and perfused with 4 percent buffered
      paraformaldehyde. Brains were removed and post-fixed in the same fixative
      overnight. Following equilibration in 30 percent sucrose, 30 micrometer sections
      were cut in sagittal plane in freezing microtome for immunohistochemistry and 20
      micrometer from plastic embedded brains. Thioflavin-S confirmed the presence of
      amyloid plaques in the Tg2576 mice. Cell proliferation in the subventricular zone
      and dentate gyrus of hippocampus were observed with Ki-67 and doublecortin
      markers. Using optical fractionator, total granule number was estimated to be
      445,280 per hemisphere in the 18-month-old Tg2576 mouse. Cell proliferation tends
      to end in the dentate gyrus but continues in the SVZ and the total granule cell
      number was less compared to normal laboratory and wild rodents.

PMID- 21196945
TI  - Effects of chronic forced swim stress on hippocampal brain-derived neutrophic
      factor (BDNF) and its receptor (TrkB) immunoreactive cells in juvenile and aged
      rats.
AB  - A type of stress stimulation and age are claimed to affect the expression of
      brain-derived neurotrophic factor (BDNF) and its receptor - tyrosine kinase B
      (TrkB) in the hippocampal regions differentially. This study aimed to explore the
      influence of chronic (15 min daily for 21 days) forced swim stress (FS) exposure
      on the BDNF and TrkB containing neurons in the hippocampal CA1, CA3 pyramidal
      cell layers and dentate gyrus (DG) granule cell layer in juvenile (P28) and aged
      (P360) rats. An immunofluorescence (-ir) method was used to detect BDNF-ir and
      TrkB-ir cells. Under chronic FS exposure, in the group of juvenile rats a
      significant decrease in the density of BDNF immunoreactive neurons was observed
      in CA1 and DG (P less than <0.001), unlike CA3, where it remained unaltered just
      as the density of TrkB-ir cells in CA1 and DG, but in CA3 the number of TrkB-ir
      cells was found to grow (P less than 0.05) in comparison with control groups.
      After chronic FS exposure of aged (P360) rats, the density of BDNF-ir and TrkB-ir
      cells did not decline in any of the subregions of the hippocampus. In all
      subfields of the hippocampus, the denseness of BDNF-positive neurons was
      significantly higher in P360 stressed group, compared with P28 stressed group,
      but the density of TrkB-ir fell more markedly in P360 than in P28. In conclusion,
      chronic FS stress influenced the number of BDNF and TrkB immunoreactive neurons
      only in juvenile animals. The age of rats tested in the chronic forced swim test
      was a decisive factor determining changes in the density of BDNF-ir and TrkB-ir
      in the hippocampal structures.

PMID- 21196946
TI  - Short-duration swimming exercise decreases penicillin-induced epileptiform ECoG
      activity in rats.
AB  - The aim of the present study is to understand the basic relationship between
      swimming exercise and natural course of epilepsy in animals by performing an
      electrophysiological study. For this purpose, male Wistar rats were submitted to
      daily swimming exercise program of three different durations. Animals were swim
      exercised for 90 days with either 15 minutes, 30 minutes or 60 minutes/day.
      Thereafter, the epileptiform activity was induced by a single microinjection of
      penicillin (500 units) into the left somatomotor cortex. Short-duration swimming
      exercise (15 min per day for 90 days) decreased the mean frequency and amplitude
      of penicillin-induced epileptiform activity in the 70 and 90 minutes after
      penicillin injection compared to penicillin administered group, respectively.
      Moderate-duration (30 min per day for 90 days) and long-duration (60 min per day
      for 90 days) swimming exercise did not alter either the frequency or amplitude of
      epileptiform activity. The results of the present study provide
      electrophysiologic evidence that short-duration swimming exercise partially
      inhibits penicillin-induced epileptiform activity. These data also suggest that
      moderate and long-duration swimming exercise do not increase either the frequency
      or severity of seizure in the model of penicillin-induced epilepsy.

PMID- 21196948
TI  - Differential startle magnitude in mice selected for high and low swim analgesia
      is not related to difference in nociception.
AB  - The acoustic startle response (ASR) elicited by 110 dB 10-ms pulses was studied
      in relation to pain sensitivity in mouse lines selectively bred for high (HA) and
      for low (LA) swim analgesia. The magnitudes of ASR, similarly as hot-plate
      latencies, differed between the lines in the rank order HA is greater than
      unselected controls (C) greater than LA. The animals' nociception did not change
      after the ASR session consisting of a sequence of 20 acoustic stimuli. Morphine
      hydrochloride (5 and 10 mg per kg i.p.) increased hot-plate latencies in the
      order of HA greater than C greater than LA, and was not effective on ASR
      magnitude in HA as well as in C mice. In the LA line, 10 mg per kg of morphine
      slightly attenuated ASR, but caused only a little analgesia. We conclude that (1)
      the difference in ASR between the selected lines is inversely correlated with the
      difference in pain sensitivity; (2) the magnitude of ASR is not altered by
      morphine analgesia; (3) the procedure of ASR using brief acoustic pulses is not
      stressful enough to elicit a form of stress analgesia. The lack of a direct
      relationship between the readiness to startle and pain sensation may be
      beneficial for an animal's survival in dangerous situations. It is beneficial
      when the startle to a warning signal precedes defensive behaviors and it often
      must be effectuated in a state of decreased nociception.

PMID- 21196947
TI  - Anticonvulsant effect of celecoxib on pentylenetetrazole-induced convulsion:
      Modulation by NO pathway.
AB  - This study aimed to examine whether celecoxib influences clonic seizure
      thresholds through modulation of nitric oxidergic (NO) pathway. The effect of
      celecoxib (1-5 mg per kg, p.o.) was investigated on clonic seizures induced by
      pentylenetetrazole (PTZ, 50 and 80 mg per kg, i.p.) in male Swiss mice. The
      interaction of celecoxib-induced effects with NO pathway was examined using a NO
      synthase (NOS) inhibitor, N(G)-omega-nitro-L-arginine methyl ester (L-NAME, 20
      and 50 mg per kg, i.p.) and a NOS substrate, L-arginine (100 and 200 mg per kg,
      i.p.). The criteria for the development of seizure activity were the possibility
      for appearance of generalized clonus and prolongation of latency to the onset of
      convulsions following administration of 50 and 80 mg per kg of PTZ, respectively.
      Pretreatment with celecoxib (2.5 and 5 mg per kg) or L-NAME (50 mg per kg)
      induced anticonvulsant effect on the PTZ-induced clonic seizures. L-arginine at
      the dose of 200 mg per kg had proconvulsant effect. A sub-effective dose of
      celecoxib (1 mg per kg) induced an additive anticonvulsant effect when co
      administered with L-NAME (20 mg per kg). Although L-arginine (100 mg per kg) per
      se did not influence PTZ-induced convulsion, it could attenuate the
      anticonvulsant effect of celecoxib (5 mg per kg). Our results indicate that
      celecoxib induces an anticonvulsant effect on clonic seizure threshold that may
      involve NO pathway.

PMID- 21196949
TI  - Neural substrate of the cognitive and emotional interference processing in
      healthy adolescents.
AB  - Emotion regulation is essential for adaptive functioning and social integration.
      However, it is not clear to what extent the responsible brain mechanisms are
      similar to those invoked in cognitive control in a non-emotional context. The aim
      of this study was to compare the neural circuitry of cognitive and emotional
      interference resolution in healthy adolescents, employing variants of the
      counting Stroop task. Cognitive and emotional interference processing engaged
      predominantly brain regions belonging to the dorsal- and the ventral attentional
      systems, respectively, and commonly the inferior frontal gyrus, IFG (Broca's
      area, left BA 45, but also right BA 45). These results suggest that BA 45 is a
      bridge of interaction between the dorsal- and the ventral attentional systems
      implicated in top-down orienting of attention and, respectively, in bottom-up
      processing of salient stimuli. Reaction time data showed that some participants
      tend to respond faster, while others respond slower to negative emotional
      compared to neutral trials. The emotional interference maps revealed that fast
      responders recruit the right temporo-parietal junction and to a larger extent the
      right BA 45 and the bilateral cuneus, suggesting that they engage more efficient
      cognitive control mechanisms to override the attentional bias. No anterior
      cingulate (ACC) activation was observed in either cognitive, or emotional
      interference; this supports the view that ACC is not involved specifically in
      mediating Stroop selection.

PMID- 21196950
TI  - Determinants of filled/empty optical illusion: Search for the locus of maximal
      effect.
AB  - A subdivided path in the visual field usually appears longer than an empty path
      of the same length. This phenomenon, known as the filled/empty or Oppel-Kundt
      illusion, depends on multiple properties of the visual stimulus, but the
      functional dependences have not been yet precisely characterized. We studied the
      illusory effect as a function of its two main determinants, the height of
      vertical strokes subdividing a spatial interval of a fixed length (visual angle
      2.8 degree) and the number of the filling strokes, using the standard-variable
      distance matching paradigm. Non-monotonic dependence of the effect (over
      reproduction of the spatial extension) on the varied parameters was observed in
      two experimental series. In the first series, the maximum effect was obtained for
      the fillers height roughly equal to the delimiters height (visual angle 0.25
      degree); in the second series, the maximum effect was obtained for 11-13
      equispaced fillers, and more accurately estimated to 15-16 as a result of a
      functional fit. Both data series were successfully modeled by curves generated by
      a single two-parametric system of form functions. Problems of determination of
      the maximum effect are discussed, and arguments for a genuinely multivariate
      approach are presented.

PMID- 21196952
TI  - Neurotrophins and their receptors in early development of the mammalian nervous
      system.
AB  - Neurotrophins belonging to the class of growth factors and including nerve growth
      factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and
      neurotrophin-4/5 (NT-4/5) are widely recognized as essential factors in the
      developing central nervous system (CNS). Neurotrophins are synthesized as
      precursor forms (proneurotrophins). Mature forms of neurotrophins exert their
      effect by binding to specific tyrosine kinases receptors (TrkA, TrkB and TrkC) as
      well as via the p75 receptor, a member of the tumor necrosis factor receptor
      superfamily while proneurotrophins interact with the receptor p75 or co-receptor
      complex of p75 and sortilin, that is a Vps10p domain-containing transmembrane
      protein. Expression of neurotrophins corresponds with the onset of neurogenesis
      in developing mammalian species. BDNF is low in early embryonic stages of
      development, while NT-3 highly expresses in the developing CNS. Expression of
      neurotrophins receptors mainly overlaps at early development. Data concerning
      early distribution of neurotrophins and their receptors in the nervous system and
      results in mice with targeted disruptions of neurotrophin or receptor genes show
      that neurotrophins and their receptors play distinct roles in control and
      regulation of the most crucial developmental processes such as proliferation,
      migration, differentiation, survival, apoptosis and synaptic plasticity.

PMID- 21196951
TI  - Why the leash constrains the dog: the impact of semantic associations on sentence
      production.
AB  - The production of language is one of the most complex and amazing skills in
      humans. Increasing evidence demonstrated that associative relations (e.g., car -
      garage) play an important role during concept formation but during speech
      production the effects and processing of associations are highly debated. Hence,
      the present study investigated the impact of associations and different SOAs on
      the production of sentences (Experiment 1) and on naming objects (Experiment 2).
      In an adapted version of the picture-word interference task, participants were
      asked to name two pictures using a standardized sentence (e.g., "The car is to
      the left of the trousers"). Thereby, a simultaneous (SOA is 0 ms) or slightly
      preceding (SOA is -150 ms) auditory or visual distractor had to be ignored.
      Distractors were related to the first noun (for example: "The car is to the left
      to the trousers", distractor: "garage") or to the second noun (distractor:
      "belt") or unrelated to both nouns (distractor: "bottle") of the sentence. At
      simultaneous presentation, visual and auditory distractors related to the first
      noun of the sentence prolonged naming responses (i.e., interference). For
      slightly preceding distractors, only visual presentation induced interference for
      the first noun of the sentence. During no condition, longer naming responses were
      found for the second noun of the sentence. These effects suggest that
      associatively related concepts are active during speech production and can be
      competitors, i.e., they lead to semantic interference. In Experiment 2, subjects
      had to name an object (e.g., car) while ignoring a visually presented distractor
      (e.g., motor). The stimulus set was the same as in Experiment 1. The results
      showed a facilitation effect if the distractor and the target were associatively
      related. Overall, the current results provide new insight in the models of speech
      production: while during single word production, associations facilitate naming,
      they interfere during sentence production. Hence, associations have an important
      influence on producing speech but the impact is varied by the context, i.e.,
      single word or sentential.

PMID- 21196953
TI  - Experimental evidence of cut-wire-induced enhanced transmission of transverse
      electric fields through sub-wavelength slits in a thin metallic screen.
AB  - Recent numerical studies have demonstrated the possibility of achieving
      substantial enhancements in the transmission of transverse-electric-polarized
      electromagnetic fields through subwavelength slits in a thin metallic screen by
      placing single or paired metallic cut-wire arrays at a close distance from the
      screen. In this paper, we report on the first experimental evidence of such
      extraordinary transmission phenomena, via microwave (X/Ku-band) measurements on
      printed-circuit-board prototypes. Experimental results agree very well with full
      wave numerical predictions, and indicate an intrinsic robustness of the enhanced
      transmission phenomena with respect to fabrication tolerances and experimental
      imperfections.

PMID- 21196954
TI  - On-the-fly cross flow laser guided separation of aerosol particles based on size,
      refractive index and density-theoretical analysis.
AB  - Laser separation of particles is achieved using forces resulting from the
      momentum exchange between particles and photons constituting the laser radiation.
      Particles can experience different optical forces depending on their size and/or
      optical properties, such as refractive index. Thus, particles can move at
      different speeds in the presence of an optical force, leading to spatial
      separations. In this paper, we present a theoretical analysis on laser separation
      of non-absorbing aerosol particles moving at speeds (1-10 cm/sec) which are
      several orders of magnitude greater than typical particle speeds used in previous
      studies in liquid medium. The calculations are presented for particle deflection
      by a loosely focused Gaussian 1064 nm laser, which simultaneously holds and
      deflects particles entrained in flow perpendicular to their direction of travel.
      The gradient force holds the particles against the viscous drag for a short
      period of time. The scattering force simultaneously pushes the particles,
      perpendicular to the flow, during this period. Our calculations show particle
      deflections of over 2500 um for 15 um aerosol particles, and a separation of over
      1500 um between 5 um and 10 um particles when the laser is operated at 10 W. We
      show that a separation of about 421 um can be achieved between two particles of
      the same size (10 um) but having a refractive index difference of 0.1. Density
      based separations are also possible. Two 10 um particles with a density
      difference of 600 kg/m3 can be separated by 193 um. Examples are shown for
      separation distances between polystyrene, poly(methylmethacrylate), silica and
      water particles. These large laser guided deflections represent a novel
      achievement for optical separation in the gas phase.

PMID- 21196955
TI  - Multiple pulse nanosecond laser induced damage study in LiB3O5 crystals.
AB  - Multiple pulse nanosecond laser induced damage in the bulk of LiB3O5 (LBO)
      crystals was investigated at 1064 nm, 532 nm and 355 nm. Scanning electron
      microscopy of cleaved damage sites confirmed the presence of different zones that
      have already been reported in the case of KH2PO4 (KDP). Multi pulse measurements
      reveal a strong decrease of the damage threshold with increasing pulse number at
      1064 nm (fatigue effect). A weaker fatigue effect was observed at 532 nm and no
      fatigue effect was found at 355 nm. This observation is best explained by an
      inherently statistical light matter interaction generating laser induced damage.
      Finally, a polarization dependent damage threshold anisotropy was evidenced at
      all three wavelengths, being strongest at 1064 nm. The results indicate the
      importance of Li+ vacancy stabilized color centers for the damage mechanism.

PMID- 21196956
TI  - Improvement of lens axicon's performance for longitudinally polarized beam
      generation by adding a dedicated phase transmittance.
AB  - The focal field of high NA lens axicon with a binary-phase optical component is
      calculated by using vector diffraction theory. Numerical results show that for a
      radially polarized Bessel Gaussian input field, the proposed system generates a
      subwavelength (0.395lambda) longitudinally polarized beam with large uniform
      depth of focus (approximately 6 lambda).

PMID- 21196957
TI  - Generalized Fourier analysis for phase retrieval of fringe pattern.
AB  - A generalized Fourier analysis, by use of an adaptive multiscale windowed Fourier
      transform (AWFT), has been presented for the phase retrieval of fringe patterns.
      The Fourier transform method can be considered as a special case of AWFT method
      with a maximum window. The instantaneous frequency of the local signal is
      introduced to estimate whether the condition for separating the first spectrum
      component is satisfied for the phase retrieval of fringe patterns. The adaptive
      window width for this algorithm is determined by the length of the local
      stationary fringe pattern in order to balance the frequency and space resolution.
      The local stationary length of fringe pattern is defined as the signal satisfying
      the condition that whose first spectrum component is separated from all the other
      spectra within the local spatial area. In comparison with Fourier transform,
      fixed windowed Fourier transform and wavelet transform in numerical simulation
      and experiment, the adaptive multiscale windowed Fourier transform can present
      more accurate results of phase retrieval.

PMID- 21196958
TI  - All-fiber frequency-stabilized erbium doped ring laser.
AB  - We present an all-fiber frequency-stabilized ring laser system with an integrated
      reference gas cell consisting of a hollow core fiber filled with acetylene.
      Through nonlinear absorption spectroscopy the laser frequency is stabilized to a
      specific absorption line of acetylene. Three different stabilization schemes are
      investigated and the minimum Allan deviation obtained after 100 s is 4.4 . 10(
      11).

PMID- 21196959
TI  - Nonlinear coupling in triangular triple-core photonic crystal fibers.
AB  - We report on a numerical analysis of the nonlinear coupling characteristics in
      triangular triple-core photonic crystal fibers (TTC-PCFs) by using coupled mode
      theory. The results show that the coupling of the TTC-PCFs exhibit more excellent
      power selectivity than that of the dual-core PCF and sharper optical switching
      and coupling-band with lower critical power are implemented in asymmetric TTC
      PCF. By adjusting the parameters of the TTC-PCF structure and length, a coupling
      band power controlled with better flatness will be obtained, in which more than
      90% input power can be transferred. These results maybe offer a new possibility
      for application fields including optical switching, pulse shaping and pulse
      compressing.

PMID- 21196960
TI  - The influence of index-depressions in core-pumped Yb-doped large pitch fibers.
AB  - Rare-earth doped photonic crystal fibers rely ideally on an index matching of the
      doped core to the surrounding glass to work properly. Obtaining a perfect index
      matching is technologically very challenging, and fiber manufacturers opt for
      targeting an index depression instead, which still ensures the influence of the
      photonic structure on the light propagation. In this paper the analysis of the
      influence of this core index depression on the higher-order mode discrimination
      and on the beam quality of the fundamental mode of different designs of core
      pumped active large pitch photonic crystal fibers is discussed. The most
      promising design is evaluated in terms of mode area scaling with a view to mode
      field diameters above 100 um. Detailed requirements on the accuracy of the core
      index matching are deduced.

PMID- 21196961
TI  - Excited-state enhancement of third-order optical nonlinearities: photodynamics
      and characterization.
AB  - Based on the simplified five-level rate-equation theory, we investigate the
      hybrid third-order optical nonlinear processes which combine the instantaneous
      nonlinearity and the one-photon absorption induced excited-state nonlinearity. We
      obtain the analytical third-order nonlinear absorption and refraction
      coefficients originating from the singlet and triplet excited-state effects. We
      explore the photodynamic process and give the corresponding level diagram in the
      nanosecond, picosecond, and femtosecond regimes. We develop the pulse-duration
      dependent Z-scan theory for characterizing the simultaneous instantaneous
      nonlinearity and cumulative effect of the excited-state nonlinearity. We also
      demonstrate the validity of the presented theory to analyze the experimental
      results.

PMID- 21196962
TI  - The use of India ink in tissue-simulating phantoms.
AB  - The optical properties of India ink, an absorber often used in preparation of
      tissue simulating phantoms, have been investigated at visible and near infrared
      wavelengths. The extinction coefficient has been obtained from measurements of
      collimated transmittance and from spectrophotometric measurements, the absorption
      coefficient from multidistance measurements of fluence rate in a diffusive
      infinite medium with small concentrations of added ink. Measurements have been
      carried out on samples of India ink from five different brands, and for some
      brands also from different batches. As also reported in previously published
      papers the results we have obtained showed large inter-brand and inter-batch
      variations for both the absorption and the extinction coefficient. On the
      contrary, our results showed small variations for the ratio between the
      absorption and the extinction coefficient. The albedo is therefore similar for
      all samples: The values averaged over all samples investigated were 0.161, 0.115,
      and 0.115 at lambda = 632.8, 751, and 833 nm respectively, with maximum
      deviations of 0.044, 0.019, and 0.035. These results indicate that, using the
      values we have obtained for the albedo, it should be possible to obtain with
      uncertainty smaller than about 4% the absorption coefficient of a sample of
      unknown ink from simple measurements of extinction coefficient. A similar
      accuracy is not easily obtained with the complicated procedures necessary for
      measurements of absorption coefficient.

PMID- 21196963
TI  - Transient full-field vibration measurement using spectroscopical stereo
      photogrammetry.
AB  - Contrasted with other vibration measurement methods, a novel spectroscopical
      photogrammetric approach is proposed. Two colored light filters and a CCD color
      camera are used to achieve the function of two traditional cameras. Then a new
      calibration method is presented. It focuses on the vibrating object rather than
      the camera and has the advantage of more accuracy than traditional camera
      calibration. The test results have shown an accuracy of 0.02 mm.

PMID- 21196964
TI  - Voltage controlled photoluminescence blinking in CdSe nano-particles.
AB  - Voltage controlled photoluminescence (PL) blinking behavior in CdSe nano
      particles (NPs) is studied. The NPs are sandwiched between a p-type silicon
      substrate and a thin Au electrode, which serve respectively as source and drain
      electrodes. The blinking PL from the NPs can be controlled by the bias voltage
      across the two electrodes. However, luminescence diminishes when photo excitation
      power is weak or bias is lower than a threshold voltage. The observed PL blinking
      is explained by a circuit model, which involves charge tunneling, Fowler-Nordheim
      (F-N) emission, and charging effect. The blinking intensity is controlled by the
      number of F-N emitted electrons whereas the pulse interval is associated with the
      time required for hole accumulation in the NPs. The intensity of luminescence
      blinking for NP clusters is found to be much higher compared to that of blinking
      from isolated NPs. This is explained by a collective recombination of F-N emitted
      electrons and accumulated holes in the NP clusters. This study provides a simple
      way of controlling PL blinking.

PMID- 21196965
TI  - Near-field and far-field analysis of an azimuthally polarized slow Bloch mode
      microlaser.
AB  - We report on the near- and far-field investigation of the slow Bloch modes
      associated with the Gamma point of the Brillouin zone, for a honeycomb lattice
      photonic crystal, using near-field scanning optical microscopy (NSOM) and infra
      red CCD camera. The array of doughnut-shaped monopolar mode (mode M) inside each
      unit cell, predicted previously by numerical simulation, is experimentally
      observed in the near-field by means of a metal-coated NSOM tip. In far-field, we
      detect the azimuthal polarization of the doughnut laser beam due to destructive
      and constructive interference of the mode radiating from the surface (mode
      TEM(01*)). A divergence of 2 degrees  for the laser beam and a mode size of (12.8
      +/- 1) um for the slow Bloch mode at the surface of the crystal are also
      estimated.

PMID- 21196966
TI  - Brightness field distributions of microlens arrays using micro molding.
AB  - This study describes the brightness field distributions of microlens arrays
      fabricated by micro injection molding (MUIM) and micro injection-compression
      molding (MUICM). The process for fabricating microlens arrays used room
      temperature imprint lithography, photoresist reflow, electroforming, MUIM, MUICM,
      and optical properties measurement. Analytical results indicate that the
      brightness field distribution of the molded microlens arrays generated by MUICM
      is better than those made using MUIM. Our results further demonstrate that mold
      temperature is the most important processing parameter for brightness field
      distribution of molded microlens arrays made by MUIM or MUICM.

PMID- 21196968
TI  - On the dielectric function tuning of random metal-dielectric nanocomposites for
      metamaterial applications.
AB  - The potential of random metal-dielectric nanocomposites as constituent elements
      of metamaterial structures is explored. Classical effective medium theories
      indicate that these composites can provide a tunable negative dielectric function
      with small absorption losses. However, the tuning potential of real random
      composites is significantly lower than the one predicted by classical theories,
      due to the underestimation of the spectral range where topological resonances
      take place. This result suggests that a random mixture consisting of a metal
      matrix with embedded isolated dielectric inclusions is a promising design
      guideline for the fabrication of tunable composites for metamaterial purposes.

PMID- 21196967
TI  - Two-photon spectral imaging with high temporal and spectral resolution.
AB  - We introduce a fast spectral imaging system using an electron-multiplying charge
      coupled device (EM-CCD) as a detector. Our system is combined with a custom-built
      two-photon excitation laser scanning microscope and has 80 detection channels,
      which allow for high spectral resolution and fast frame acquisition without any
      loss of spectral information. To demonstrate the efficiency of our approach, we
      applied this technology to monitor fluorescent proteins and quantum dot-labeled G
      protein-coupled receptors in living cells as well as autofluorescence in tissue
      samples.

PMID- 21196969
TI  - Multi-impairment monitoring from adaptive finite-impulse-response filters in a
      digital coherent receiver.
AB  - We propose a novel and unified algorithm that estimates linear impairments in
      optical transmission systems from tap coefficients of an adaptive finite-impulse
      response (FIR) filter in a coherent optical receiver. Measurable impairments
      include chromatic dispersion (CD), differential group delay (DGD) between two
      principal states of polarization, second-order polarization-mode dispersion
      (second-order PMD), and polarization-dependent loss (PDL). We validate our multi
      impairment monitoring algorithm by dual-polarization quadrature phase-shift
      keying (QPSK) transmission experiments.

PMID- 21196970
TI  - Mirrorless buried waveguide laser in monoclinic double tungstates fabricated by a
      novel combination of ion milling and liquid phase epitaxy.
AB  - Buried channel waveguides were fabricated by liquid phase epitaxial growth of a
      lattice-matched KY(0.58)Gd(0.22)Lu(0.17)Tm(0.03)(WO4)2 film on a microstructured
      KY(WO4)2 substrate. Channels were transferred to the substrates by standard
      photolithography and Ar-ion milling. The bottom and sidewalls of the milled
      channels were smooth enough (rms roughness = 70 nm and 20 nm, respectively) to
      favour the epitaxial growth of the active layer without defects at the boundary
      of substrate/epitaxial layer. The refractive index contrast was sufficient to
      enable light confinement and guided modes with low scattering losses were
      observed at wavelengths between 1440 nm and 1640 nm. CW laser operation at 1840
      nm at room temperature was observed with feedback provided only by Fresnel
      reflection at the end faces, with slope efficiencies of 4% and 9% for TE and TM
      polarizations, respectively.

PMID- 21196971
TI  - Generation of dark hollow beam via coherent combination based on adaptive optics.
AB  - A novel method for generating a dark hollow beam (DHB) is proposed and studied
      both theoretically and experimentally. A coherent combination technique for laser
      arrays is implemented based on adaptive optics (AO). A beam arraying structure
      and an active segmented mirror are designed and described. Piston errors are
      extracted by a zero-order interference detection system with the help of a custom
      made photo-detectors array. An algorithm called the extremum approach is adopted
      to calculate feedback control signals. A dynamic piston error is imported by
      LiNbO<sub>3</sub> to test the capability of the AO servo. In a closed loop the
      stable and clear DHB is obtained. The experimental results confirm the
      feasibility of the concept.

PMID- 21196972
TI  - Optical properties of one-dimensional photonic crystal with a twisted-nematic
      defect layer.
AB  - Spectral properties of an electrically tunable one-dimensional photonic crystal
      infiltrated with a twisted-nematic liquid crystal (PC/TN) are investigated. Two
      mesogenic materials with dissimilar optical anisotropies are examined for
      constituting the central defect layer. With the TN alignment of the defect layer
      embedded in the dielectric multilayers, the defect modes not only shift with the
      applied voltage but also switch between two major modes when the linear
      polarization angle of the incident light is altered. The superposition of the
      mixed-mode TN (MTN) and the photonic bandgap brings out a tremendous undulation
      in all range of the transmission spectrum. The defect modes falling at the
      centers of the MTN spectral humps are allowed to intensely transmit while the
      others are suppressed. As a result, we propose a monochromatic selector
      constructed by such a PC/MTN device with electrical tunability.

PMID- 21196973
TI  - Study of different spectral regions and delay bandwidth relation in slow light
      photonic crystal waveguides.
AB  - We investigate slow light propagation in monomode photonic crystal waveguides
      with different spectral features such as constant group index, high bandwidth and
      low group velocity dispersion. The form of the waveguide mode alters dramatically
      and spans three different spectral intervals by tuning the size of the boundary
      holes. Namely, slope of the band gap guided mode changes sign from negative to
      positive toward the Brillouin zone edge. In between there is a transition region
      where modes have nearly zero slopes. Maximum group index occurs at these turning
      points at the expense of high dispersion and narrow bandwidth. The apparent trade
      off relationship between group index and bandwidth is revealed systematically. We
      show that as the radius of the innermost hole is increased above a certain value,
      the former one decreases and the latter one increases both exponentially but with
      a different ratio. The product of average group index and bandwidth is defined as
      a figure of merit which reaches up to a value of approximately 0.30 after a
      detailed parametric search. The findings of the frequency domain analysis
      obtained by plane wave expansion method are confirmed via finite-difference time
      domain study.

PMID- 21196974
TI  - Theoretical and experimental studies of turbo product code with time diversity in
      free space optical communication.
AB  - In free space optical communication (FSOC) systems, channel fading caused by
      atmospheric turbulence degrades the system performance seriously. However,
      channel coding combined with diversity techniques can be exploited to mitigate
      channel fading. In this paper, based on the experimental study of the channel
      fading effects, we propose to use turbo product code (TPC) as the channel coding
      scheme, which features good resistance to burst errors and no error floor.
      However, only channel coding cannot cope with burst errors caused by channel
      fading, interleaving is also used. We investigate the efficiency of interleaving
      for different interleaving depths, and then the optimum interleaving depth for
      TPC is also determined. Finally, an experimental study of TPC with interleaving
      is demonstrated, and we show that TPC with interleaving can significantly
      mitigate channel fading in FSOC systems.

PMID- 21196975
TI  - Automodulations in an extended cavity, passively modelocked Ti:Sapphire
      oscillator--period doubling and chaos.
AB  - An extended cavity Ti:Sapphire oscillator exhibits stable operation for
      positively chirped pulses, while in the negative chirp regime multiple pulses are
      present in the cavity. At the border of these regimes automodulations, being an
      effect of the interplay between population inversion, laser medium polarization
      and the laser pulse field, appear. Two particular instabilities: period doubling
      and chaotic behavior of the pulse train envelope are observed. Complex temporal
      evolution of the pulse spectrum within the modulation period is investigated.

PMID- 21196976
TI  - 3D microlasers from self-assembled cholesteric liquid-crystal microdroplets.
AB  - We demonstrate a tunable and omnidirectional microlaser in the form of a
      microdroplet of a dye-doped, cholesteric liquid crystal in a carrier fluid. The
      cholesteric forms a Bragg-onion optical microcavity and the omnidirectional 3D
      lasing is due to the stimulated emission of light from the dye molecules in the
      liquid crystal. The lasing wavelength depends solely on the natural helical
      period of the cholesteric and can be tuned by varying the temperature. Millions
      of microlasers can be formed simply by mixing a liquid crystal, a laser dye and a
      carrier fluid, thus providing microlasers for soft-matter photonic devices.

PMID- 21196977
TI  - High-Q Si microresonators formed by substrate transfer on silica waveguide
      wafers.
AB  - We report the first demonstration of Si microresonators (MRs) fabricated via
      substrate transfer on a silica waveguide (WG) wafer. Specifically, these Si
      microdisks were fabricated on a layer of Si (0.16-0.2 MUm thick) that was
      directly-bonded on a silica waveguide wafer. We measured the throughput and drop
      spectrum of these microdisks when coupled to bonded silica waveguides, and
      observed loaded quality-factors (Qs) of >=10(4). We modeled, in addition, the
      dispersion of whispering gallery modes in these microdisks to show phase-matched
      coupling with an incident silica waveguide or fiber-taper. Using the measured
      extinction ratio and loaded-Q, we evaluated, in addition, the coupling
      coefficient between the incident waveguide/taper and Si MR.

PMID- 21196978
TI  - A numerical analysis method for evaluating rod lenses using the Monte Carlo
      method.
AB  - We propose a numerical analysis method for evaluating GRIN lenses using the Monte
      Carlo method. Actual measurements of the modulation transfer function (MTF) of a
      GRIN lens using this method closely match those made by conventional methods.
      Experimentally, the MTF is measured using a square wave chart, and is then
      calculated based on the distribution of output strength on the chart. In
      contrast, the general method using computers evaluates the MTF based on a spot
      diagram made by an incident point light source. However the results differ
      greatly from those from experiments. We therefore developed an evaluation method
      similar to the experimental system based on the Monte Carlo method and verified
      that it more closely matches the experimental results than the conventional
      method.

PMID- 21196979
TI  - Two-color multi-section quantum dot distributed feedback laser.
AB  - A dual-wavelength emission source is realized by asymmetrically pumping a two
      section quantum-dot distributed feedback laser. It is found that under asymmetric
      bias conditions, the powers between the ground-state and excited-state modes of
      the two-section device can be equalized, which is mainly attributed to the unique
      carrier dynamics of the quantum-dot gain medium. As a result, a two-color
      emission with an 8-THz frequency difference is realized that has potential as a
      compact THz source. It is also shown that the combination of significant
      inhomogeneous broadening and excited-state coupled mode operation allows the
      manipulation of the quantum-dot states through external optical stabilization.

PMID- 21196980
TI  - Packed domain Rayleigh-Sommerfeld wavefield propagation for large targets.
AB  - For applications in the domain of digital holographic microscopy, we present a
      fast algorithm to propagate scalar wave fields from a small source area to an
      extended, parallel target area of coarser sampling pitch, using the first
      Rayleigh-Sommerfeld diffraction formula. Our algorithm can take full advantage of
      the fast Fourier transform by decomposing the convolution kernel of the
      propagation into several convolution kernel patches. Using partial overlapping of
      the patches together with a soft blending function, the Fourier spectrum of these
      patches can be reduced to a low number of significant components, which can be
      stored in a compact sparse array structure. This allows for rapid evaluation of
      the partial convolution results by skipping over negligible components through
      the Fourier domain pointwise multiplication and direct mapping of the remaining
      multiplication results into a Fourier domain representation of the coarsly
      sampled target patch. The algorithm has been verified experimentally at a
      numerical aperture of 0.62, not showing any significant resolution limitations.

PMID- 21196981
TI  - Hybrid orthogonal junctions: wideband plasmonic slot-silicon waveguide couplers.
AB  - In this paper, novel ultra compact and ultra wide band couplers between silicon
      and plasmonic slot waveguides are analyzed, characterized, and fabricated. This
      novel coupling scheme is fabricated using silicon on insulator platform. An
      orthogonal junction configuration is designed to provide non-resonate wideband
      coupling from a 400 nm silicon waveguide to 50-nm wide air-filled plasmonic slot.
      The 1 MUm wide full-width half-max coupling spectrum can theoretically reach high
      peak of 70% coupling to the plasmonic slot centered around the 1550 nm
      wavelength. This center wavelength can be controlled by varying the silicon
      waveguide width. Theoretical analysis is in good agreement with FDTD simulated
      results, and experimental results. The fabrication procedure is also presented
      and discussed.

PMID- 21196982
TI  - Design of invisibility cloaks with an open tunnel.
AB  - In this paper we apply the methodology of transformation optics for design of a
      novel invisibility cloak which can possess an open tunnel. Such a cloak
      facilitates the insertion (retrieval) of matter into (from) the cloak's interior
      without significantly affecting the cloak's performance, overcoming the matter
      exchange bottleneck inherent to most previously proposed cloak designs.We achieve
      this by applying a transformation which expands a point at the origin in
      electromagnetic space to a finite area in physical space in a highly anisotropic
      manner. The invisibility performance of the proposed cloak is verified by using
      full-wave finite-element simulations.

PMID- 21196983
TI  - Enhancing signal detection and completely eliminating scattering using quasi
      phase-cycling in 2D IR experiments.
AB  - We demonstrate how quasi-phase-cycling achieved by sub-cycle delay modulation can
      be used to replace optical chopping in a box-CARS 2D IR experiment in order to
      enhance the signal size, and, at the same time, completely eliminate any
      scattering contamination. Two optical devices are described that can be used for
      this purpose, a wobbling Brewster window and a photoelastic modulator. They are
      simple to construct, easy to incorporate into any existing 2D IR setup, and have
      attractive features such as a high optical throughput and a fast modulation
      frequency needed to phase cycle on a shot-to-shot basis.

PMID- 21196984
TI  - Designs of broadband and wide-view patterned polarizers for stereoscopic 3D
      displays.
AB  - This work presents a new methodology to design patterned circular polarizers
      consisting of in-cell polarizers, in-cell retarders and biaxial films to achieve
      very wide viewing freedom for stereoscopic 3D color LCDs. The biaxial films with
      least materials and simple fabrication concepts are employed for off-axis
      compensation of the in-cell retarders. In the best result, the crosstalk ratio is
      less than 0.035 or 0.0082 respectively for over +/- 60 degrees  or +/- 40 degrees
      viewing cone of the 3D display. As to the normal view of the proposed structure
      with glasses or LCD rotation, the crosstalk ratio is less than 0.11%, with 93.5%
      improvement as compared with the +/- lambda/4 patterned polarizer. The dispersion
      properties of materials have been considered in all simulations to mimic real
      situations.

PMID- 21196985
TI  - Space-based optical image encryption.
AB  - In this paper, we propose a new method based on a three-dimensional (3D) space
      based strategy for the optical image encryption. The two-dimensional (2D)
      processing of a plaintext in the conventional optical encryption methods is
      extended to a 3D space-based processing. Each pixel of the plaintext is
      considered as one particle in the proposed space-based optical image encryption,
      and the diffraction of all particles forms an object wave in the phase-shifting
      digital holography. The effectiveness and advantages of the proposed method are
      demonstrated by numerical results. The proposed method can provide a new optical
      encryption strategy instead of the conventional 2D processing, and may open up a
      new research perspective for the optical image encryption.

PMID- 21196986
TI  - Generalized Stokes parameters of rectangular hard-edge diffracted random
      electromagnetic beams.
AB  - Based on the complex Gaussian expansion method for two dimensional rectangular
      hard-edged aperture, the analytical formulas for the generalized Stokes
      parameters of random electromagnetic beams through a paraxial ABCD optical system
      with rectangular hard-edged aperture are derived. With the help of the analytical
      formulae, the changes in statistical properties of rectangular hard-edge
      diffracted random electromagnetic beams, such as in the spectral density, in the
      spectral degree of coherence, in the polarization properties and so on, can be
      determined. Numerical examples of such changes are presented and discussed.

PMID- 21196987
TI  - Room temperature continuous wave milliwatt terahertz source.
AB  - We present a continuous wave terahertz source based on intracavity difference
      frequency generation within a dual color vertical external cavity surface
      emitting laser. Using a nonlinear crystal with a surface emitting phase matching
      scheme allows for high conversion efficiencies. Due to the tunability of the dual
      mode spacing, the entire spectral range of the terahertz gap can be covered. The
      terahertz output scales quadratically with the intracavity intensity, potentially
      allowing for terahertz intensities in the range of 10s of milliwatts and beyond.

PMID- 21196988
TI  - On resolution and viewing of holographic image generated by 3D holographic
      display.
AB  - In the paper Wigner Distribution (WD) representation analysis of holographic
      display is presented. The display reconstructs holographic image by means of
      Spatial Light Modulator. Two major aspects are covered: imaging and viewing.
      Optically reconstructed images are characterized by low and spatially variant
      resolution. Utilizing WD representation we present a simple formula for
      resolution as a function of both coordinates: transverse and longitudinal. The
      analysis of an aliasing effect allows for meaningful extension of the field of
      view. All theoretical results are proven experimentally. The WD representation of
      angularly and spatially limited holographic image is extended to cover its visual
      perception as well. Angular resolution and field of view are theoretically
      examined. Both monocular and binocular perception are studied and illustrated
      experimentally.

PMID- 21196989
TI  - Intense ultra-broadband down-conversion from randomly poled nonlinear crystals.
AB  - Randomly poled nonlinear crystals are shown to be able to emit intense ultra
      broadband photon-pair fields with properties comparable to those coming from
      chirped periodically-poled crystals. Their intensities scale linearly with the
      number of domains. Also photon pairs extending over intervals with durations
      comparable to one optical cycle can be generated in these crystals.

PMID- 21196990
TI  - Estimation of relative defect densities in InGaN laser diodes by induced
      absorption of photoexcited carriers.
AB  - Defects are one of the most important factors influencing the optical properties
      of groups III-V nitride semiconductor materials and thereby their applicability
      to light-emitting diodes. In this paper, we demonstrate that it is possible to
      estimate the presence of defects in InGaN laser diodes by performing pump-probe
      measurements and observing the induced absorptions. We have confirmed that the
      induced absorption originates from defects by performing experiments in which the
      pump intensity is varied. We believe that our method provides a powerful tool for
      evaluating the optical quality of InGaN materials before processing them into
      device fabrications.

PMID- 21196991
TI  - Fast photogalvanic response of a Bi12SiO20 crystal.
AB  - A photoelectric response of a Bi12SiO20 crystal grown in an argon atmosphere on a
      linearly polarized light (which is referred to as the linear photogalvanic
      effect) is reported for the first time in the nanosecond-time domain. Optimal
      geometry for detection of the photo-induced current concerning the orientation of
      the polarization state of the incident light in respect to the crystallographic
      axes of a sample was determined considering both the natural optical activity and
      light absorption of sillenite crystals. Spectral dependence of the photogalvanic
      current was measured in the visible part (410 - 610 nm) of the spectrum. Temporal
      shape of light-induced electric-current pulses observed at different experimental
      conditions is discussed. Obtained results are believed to show that sillenite
      crystals are very prospective for development of different ultra-fast
      optoelectronics devices.

PMID- 21196992
TI  - Terahertz multichanneled filter in a superconducting photonic crystal.
AB  - Terahertz spectroscopic properties in a one-dimensional superconductor-dielectric
      photonic crystal are theoretically investigated. Based on the calculated results,
      a terahertz multichanneled transmission filter can be achieved within the
      photonic passband. This structure possesses the comb-like resonant peaks in
      transmission spectrum at low temperature. The number of resonant peaks is
      directly related to the number of periods. The resonant peak height is lowered
      and broadened as the temperature increases. The dependence of the filling factor
      in the superconductor layer is also discussed. This filter containing no defect
      layer in structure is fundamentally different from the usual multichanneled
      filter based on a photonic crystal containing a photonic quantum well as a defect
      layer.

PMID- 21196993
TI  - Femtotesla atomic magnetometry in a microfabricated vapor cell.
AB  - We describe an optically pumped 87Rb magnetometer with 5 fT/Hz(1/2) sensitivity
      when operated in the spin-exchange relaxation free (SERF) regime. The
      magnetometer uses a microfabricated vapor cell consisting of a cavity etched in a
      1 mm thick silicon wafer with anodically bonded Pyrex windows. The measurement
      volume of the magnetometer is 1 mm3, defined by the overlap region of a
      circularly polarized pump laser and a linearly polarized probe laser, both
      operated near 795 nm. Sensitivity limitations unique to the use of
      microfabricated cells are discussed.

PMID- 21196994
TI  - Imaging true 3D endoscopic anatomy by incorporating magnetic tracking with
      optical coherence tomography: proof-of-principle for airways.
AB  - Endoscopic imaging using optical coherence tomography (OCT) has been demonstrated
      as clinically useful in the assessment of human airways. These airways have a
      complex 3D structure, bending, tapering and bifurcating. Previously published 3D
      OCT reconstructions have not accounted for changes in the orientation and
      trajectory of the endoscopic probe as it moves through the airway during imaging.
      We propose a novel endoscopic setup incorporating a magnetic tracking system that
      accounts for these changes, yielding reconstructions that reveal the true 3D
      nature of the imaged anatomy. We characterize the accuracy of the system, and
      present the first published magnetic tracker-assisted endoscopic OCT
      reconstructions using a phantom airway.

PMID- 21196995
TI  - Low power consumption integrated acousto-optic filter in domain inverted LiNbO3
      superlattice.
AB  - We report on an integrated acousto-optic filter in domain inverted LiNbO3 using a
      coplanar electrode configuration, which can achieve complete optical switching at
      electrical powers as low as 50 mW. These values are more than one order of
      magnitude lower than previously reported results [Opt. Lett. 34, 3205 (2009)]. In
      order to design the low power consumption devices, we have calculated surface
      acoustic wave excitation, propagation and acousto-optic interaction in the domain
      inverted LiNbO3 superlattice using scalar approximation and FEM analysis. Results
      from both modeling techniques are in good agreement with the experiments,
      including direct measurement of the acoustic displacement using laser
      interferometry and acousto-optic performance.

PMID- 21196996
TI  - Structure and luminescence evolution of annealed Europium-doped silicon oxides
      films.
AB  - Europium (Eu)-doped silicon oxide films with Eu concentrations from 2.1 to 4.7
      at. % were deposited by electron beam evaporation. The Eu related luminescence
      from the films was found to be sensitive to the evolution of film microstructures
      at different annealing temperatures. Luminescence centers in the films changed
      from defects of silicon oxides to 4f(6)5d-4f(7)(8S(7/2)) transition of Eu2+ after
      the films annealed in N2 at temperature higher than 800  degrees C. The evolution
      of luminescence centers was attributed to the formation of europium silicate
      (EuSiO3), which was confirmed by x-ray photoelectron spectroscopy, x-ray
      diffraction, time resolved photoluminescence, and transmission electron
      microscopy.

PMID- 21196997
TI  - Single-mode analysis of Yb-doped double-cladding distributed spectral filtering
      photonic crystal fibers.
AB  - Hybrid large mode area Ytterbium-doped double-cladding photonic crystal fibers
      with anti-symmetric high refractive index inclusions provide efficient amplified
      spontaneous emission spectral filtering. Their performances have been analyzed by
      numerical simulations and experimental measurements. In particular, the fiber
      single-mode behaviour has been studied, by taking into account the fundamental
      and the first higher-order mode. Two approaches, the core down-doping and the
      reduction of the air-hole diameter in the inner cladding, have been successfully
      applied to reduce the higher-order mode content, regardless of the bending of the
      doped fiber, without significantly affecting its spectral filtering properties.

PMID- 21196998
TI  - The polarizing Sagnac interferometer: a tool for light orbital angular momentum
      sorting and spin-orbit photon processing.
AB  - In this paper we show that an optical setup based on a polarizing Sagnac
      interferometer combined with a Dove prism can be used as a convenient general
      purpose tool for the generation, detection and sorting of spin-orbit states of
      light. This device can work both in the classical and in the quantum single
      photon regime, provides higher sorting efficiency and extinction ratio than usual
      hologram-fiber combinations, and shows much higher stability and ease of
      alignment than Mach-Zehnder interferometer setups. To demonstrate the full
      potential of this setup, we also report some demonstrative experiments of several
      possible applications of this setup.

PMID- 21196999
TI  - Metropolitan all-pass and inter-city quantum communication network.
AB  - We have demonstrated a metropolitan all-pass quantum communication network in
      field fiber for four nodes. Any two nodes of them can be connected in the network
      to perform quantum key distribution (QKD). An optical switching module is
      presented that enables arbitrary 2-connectivity among output ports. Integrated
      QKD terminals are worked out, which can operate either as a transmitter, a
      receiver, or even both at the same time. Furthermore, an additional link in
      another city of 60 km fiber (up to 130 km) is seamless integrated into this
      network based on a trusted relay architecture. On all the links, we have
      implemented protocol of decoy state scheme. All of necessary electrical hardware,
      synchronization, feedback control, network software, execution of QKD protocols
      are made by tailored designing, which allow a completely automatical and stable
      running. Our system has been put into operation in Hefei in August 2009, and
      publicly demonstrated during an evaluation conference on quantum network
      organized by the Chinese Academy of Sciences on August 29, 2009. Real-time voice
      telephone with one-time pad encoding between any two of the five nodes (four all
      pass nodes plus one additional node through relay) is successfully established in
      the network within 60 km.

PMID- 21197000
TI  - Near-field interaction of two-dimensional high-permittivity spherical particle
      arrays on substrate in the Mie resonance scattering domain.
AB  - We describe theoretical and experimental results on near-field interaction of two
      dimensionally (2D) arrayed, high-permittivity spherical particles on a substrate
      in the Mie resonance scattering domain for surface nano-patterning processing.
      When a touching particle pair of Mie resonance particles on the substrate is
      considered, an electromagnetic mode different from the single particle mode is
      excited inside the particles, resulting in an intensity enhancement in a gap
      between two hotspots at particle-substrate contact points. As for 2D hexagonal
      close-packed particle arrays on the substrate, the refractive index of particle
      exhibiting a maximal enhancement factor for the 2D particle arrays is found to be
      shifted from the Mie resonance conditions for the single particle system.

PMID- 21197001
TI  - Temperature dependent characterization of terahertz vibrations of explosives and
      related threat materials.
AB  - Waveguide terahertz time-domain spectroscopy (THz-TDS) is used to characterize
      the temperature dependent vibrational properties of three threat-related
      materials: 4-amino-dinitrotoluene (4A-DNT), pentaerythritol tetranitrate (PETN),
      and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX). These materials are
      characterized as thin polycrystalline layers deposited in the 50 micron gap of a
      metal parallel plate waveguide. For each material waveguide THz-TDS at least
      partially resolves the underlying vibrational spectrum and reveals new features
      that have not been observed in previous free space measurements of these
      materials. Strong experimental evidence for a phase transformation is observed
      for 4A-DNT as the polycrystalline layer on the waveguide surface is cooled to
      near 200 K. For PETN a highly resolved spectrum containing eleven vibrational
      lines is observed at 11 K with full-width at half maximum linewidths ranging from
      7 GHz to 40 GHz. Based on comparison to measurements in the literature, our PETN
      measurement suggests that it is possible to produce narrow linewidths from a
      polycrystalline layer that approach those from a single crystal. Finally, for
      HMX, a highly resolved vibrational spectrum is measured that is assigned to the
      metastable gamma polymorph.

PMID- 21197002
TI  - Imaging the in-plane magnetization in a Co microstructure by Fourier transform
      holography.
AB  - We report on experiments using Fourier transform holography to image the in-plane
      magnetization of a magnetic microstructure. Magnetic sensitivity is achieved via
      the x-ray magnetic circular dichroism effect by recording holograms in
      transmission at off-normal incidence. The reference beam is defined by a narrow
      hole milled at an inclined angle into the opaque mask. We present magnetic domain
      images of an in-plane magnetized cobalt element with a size of 2 MUm * 2 MUm* 20
      nm. The domain pattern shows a multi-vortex state that deviates from the simple
      Landau ground state.

PMID- 21197003
TI  - Blue-white-green tunable luminescence from Ba2Gd2Si4O13:Ce3+,Tb3+ phosphors
      excited by ultraviolet light.
AB  - The novel Ba2Gd2Si4O13:Ce3+,Tb3+ phosphors were systemically investigated by
      fluorescent method for the first time. Through an efficient energy transfer
      process, the obtained phosphors exhibit both a blue emission of Ce3+ and a
      yellowish green emission of Tb3+ with considerable intensity under near
      ultraviolet excitation (300-370 nm). Tuning of the content of Tb3+ can generate
      the varied hues from blue to white and eventually to yellowish green. The quantum
      efficiency of the white phosphor Ba2(Gd0.88Ce0.02Tb0.1)2Si4O13 is 82.3% of
      commercial ZnS:Ag+,Cl- phosphor. Our results demonstrate that the potential
      application of these phosphors in solid-state lighting and (or) other areas.

PMID- 21197004
TI  - Slow light with a swept-frequency source.
AB  - ct: We introduce a new concept for stimulated-Brillouin-scattering-based slow
      light in optical fibers that is applicable for broadly-tunable frequency-swept
      sources. It allows slow light to be achieved, in principle, over the entire
      transparency window of the optical fiber. We demonstrate a slow light delay of 10
      ns at 1.55 MUm using a 10-m-long photonic crystal fiber with a source sweep rate
      of 400 MHz/MUs and a pump power of 200 mW. We also show that there exists a
      maximal delay obtainable by this method, which is set by the SBS threshold,
      independent of sweep rate. For our fiber with optimum length, this maximum delay
      is ~38 ns, obtained for a pump power of 760 mW.

PMID- 21197005
TI  - Absorbing polarization selective resonant gratings.
AB  - We introduce resonant absorbers that consist of linear metal wires embedded
      inside of a titanium dioxide grating. We show that in these structures the guided
      mode resonance may lead to the almost total absorption of one polarization
      component and greatly enhance the absorption in localized surface plasma
      resonance. In addition, we show that the structures have potential to function as
      filters or polarizing beamsplitters. Absorption of 99.67 % has been obtained
      together with the contrast of 6600 at the wavelength of 532 nm. This corresponds
      the extinction of 8.8597. The results have been verified experimentally by
      fabricating an absorbing filter with electron beam lithography and atomic layer
      deposition technique. The absorption is remarkably high considering the thickness
      of the structures which is only 219-333 nm.

PMID- 21197006
TI  - Liquid crystal dynamics in a photonic crystal cavity created by selective
      microfluidic infiltration.
AB  - A microfluidic double heterostructure cavity is created in a silicon planar
      photonic crystal waveguide by selective infiltration of a liquid crystal. The
      spectral evolution of the cavity resonances probed by evanescent coupling reveals
      that the liquid crystal evaporates, even at room temperature, despite its
      relatively low vapor pressure of 5 * 10(-3) Pa. We explore the infiltration and
      evaporation dynamics of the liquid crystal within the cavity using a Fabry-Perot
      model that accounts for the joint effects of liquid volume reduction and cavity
      length variation due to liquid evaporation. While discussing how the pattern of
      the infiltrated liquid can be optimized to restrict evaporation, we find that the
      experimental behavior is consistent with basic microfluidic relations considering
      the small volumes of liquids and large surface areas present in our structure.

PMID- 21197007
TI  - Multi-MUJ, CEP-stabilized, two-cycle pulses from an OPCPA system with up to 500
      kHz repetition rate.
AB  - We present a two-stage OPCPA system based on a Ti:sapphire seed and a thin-disk
      regenerative amplifier producing compressed pulse energies of more than 3 MUJ and
      durations of less than 6 fs at a high repetition rate of 143 kHz. In combination
      with the obtained CEP stability and the repetition rate scalability between 100
      and 500 kHz the system forms an ideal tool for high field and phase sensitive
      spectroscopic experiments.

PMID- 21197008
TI  - Optical amplitude modulation extinction by a deep saturated ultra-long
      semiconductor optical amplifier.
AB  - The recovery of an optical carrier with the deletion of its amplitude modulation
      is introduced using a deeply saturated ultra-long semiconductor optical amplifier
      (UL-SOA). The experimental results were achieved for input signal bit rates up to
      12.5 Gbps with high extinction ratio (up to 13.9 dB). The influence of parameters
      such as UL-SOA bias current, optical bandwidth, signal input power, modulation
      depth and bit rate are analyzed including the carrier spectral broadening effects
      due to the self-phase modulation effect.

PMID- 21197009
TI  - In-service light path PMD (polarization mode dispersion) monitoring by PMD
      compensation.
AB  - We describe a novel method of measuring PMD (polarization mode dispersion) of an
      in-service DWDM system by PMD compensation. We successfully demonstrate the
      method in a 1500-km ultra-long haul DWDM test bed. We further verify the
      feasibility of the method for in-service light path PMD monitoring in a field
      trial in a revenue-generating route in Verizon Network, and obtain an accurate
      PMD value without impacting live network traffic. The discrepancy between the
      measured and expected PMD values is less than 6% for all cases tested.

PMID- 21197010
TI  - Conical diffraction of linearly polarised light controls the angular position of
      a microscopic object.
AB  - Conical diffraction of linearly polarised light in a biaxial crystal produces a
      beam with a crescent-shaped intensity profile. Rotation of the plane of
      polarisation produces the unique effect of spatially moving the crescent-shaped
      beam around a ring. We use this effect to trap microspheres and white blood cells
      and to position them at any angular position on the ring. Continuous motion
      around the circle is also demonstrated. This crescent beam does not require an
      interferometeric arrangement to form it, nor does it carry optical angular
      momentum. The ability to spatially locate a beam and an associated trapped object
      simply by varying the polarisation of light suggests that this optical process
      should find application in the manipulation and actuation of micro- and nano
      scale physical and biological objects.

PMID- 21197011
TI  - Hyperspectral imaging of diffracted surface plasmons.
AB  - We present the results of far field measurements of the complete 3D dispersion
      relation of a surface plasmon resonance (SPR) effect induced by an integrated
      quantum well nanodevice. The light modulations in the far field, where the
      surface plasmons are extracted by a grating, has been calculated for a continuum
      of energies and wavevectors injected by the luminescent substrate. We introduce a
      novel experimental method for direct mapping of the EM wave dispersion that
      enables the monitoring of massive amounts of light-scattering related
      information. The quasi-real time method is applied for tracking, in the E(k)
      space, the SPR peak surfaces generated by the investigated nanodevice. Those
      additional dimensions, measured with scalable tracking precision, reveal
      anisotropic surficial interactions and provide spectroscopic response for SPR.

PMID- 21197012
TI  - Enhanced THz radiation emission from plasmonic complementary Sierpinski fractal
      emitters.
AB  - We present a new class of plasmonic photoconductive THz emitters based on a
      complementary Sierpinski gasket fractal geometry. Due to the presence of sub
      wavelength perforations on the surface of the antenna, these antennae operate in
      the plasmonic regime. By utilizing the unique self-similar and space filling of
      the tailored fractal surface and the plasmonic surface current spatial
      distribution, photoconductive THz emitters exhibiting superior performance (~80%
      increase in the emitted THz radiation power) to conventional bow-tie and
      Sierpinski gasket THz emitters are demonstrated. It is shown that the self
      similarity of the surface plasmon current present on the antenna surface is
      responsible for this emission enhancement.

PMID- 21197013
TI  - Experimental and modeling studies of imaging with curvilinear electronic eye
      cameras.
AB  - Model calculations and the experimental measurements of the imaging properties of
      planar, hemispherical, and elliptic parabolic electronic eye cameras are
      compared. Numerical methods for comprehensive full field calculations of image
      formation are enabled by use computationally efficient modes. Quantitative
      agreement between these calculations and experimentally measured images of test
      patterns reveals advantages of curvilinear camera systems, and provides
      guidelines for future designs.

PMID- 21197014
TI  - A photonic chip based frequency discriminator for a high performance microwave
      photonic link.
AB  - We report a high performance phase modulation direct detection microwave photonic
      link employing a photonic chip as a frequency discriminator. The photonic chip
      consists of five optical ring resonators (ORRs) which are fully programmable
      using thermo-optical tuning. In this discriminator a drop-port response of an ORR
      is cascaded with a through response of another ORR to yield a linear phase
      modulation (PM) to intensity modulation (IM) conversion. The balanced photonic
      link employing the PM to IM conversion exhibits high second-order and third-order
      input intercept points of + 46 dBm and + 36 dBm, respectively, which are
      simultaneously achieved at one bias point.

PMID- 21197015
TI  - Role of structural electromagnetic resonances in a steerable left-handed antenna.
AB  - We reformulate the problem of a steerable left-handed antenna reported by
      Matsuzawa et al. [IEICE Trans. Electron. E89-C, 1337 (2006)] from the view point
      of structural electromagnetic resonance of the unit structure. We show that there
      are two such resonances with different spatial symmetries in the relevant
      frequency range, which result in the formation of two electromagnetic bands with
      opposite signs of curvature at the Gamma point of the Brillouin zone. We derive
      an expression of dispersion curves based on the tight-binding picture and show
      that the dispersion of the two bands is linear in the vicinity of the Gamma point
      in the case of accidental degeneracy only if the symmetry of the two resonance
      states satisfies certain conditions. We also show that the refraction angle can
      be designed by changing the lattice constant of the arrayed unit structures,
      since the band width is modified due to the change in the electromagnetic
      transfer integral.

PMID- 21197016
TI  - Solvent effect induced solute damage in an organic inner salt.
AB  - Nonlinear absorption of a newly synthesized organic inner salt Ge-150 dissolved
      in four different solvents (DMF, DMSO, acetonitrile and acetone) is investigated
      by the Z-scan technique with both nanosecond and picosecond pulses. When pulse
      energy surpasses a threshold and pulse-to-pulse separation is shorter than a
      characteristic time, all the four solutions show absorption weakening induced by
      cross-pulse effects in the picosecond regime. However, only two of them (Ge-150
      dissolved in DMF and DMSO) show this weakening in the nanosecond regime. By
      conducting a simple verification experiment, we verify this absorption weakening
      is induced by solute damage related to solvent effect rather than solute
      migration. A simple theoretical model is proposed to interpret the experimental
      phenomenon.

PMID- 21197017
TI  - Compact broadband polarizer based on shallowly-etched silicon-on-insulator ridge
      optical waveguides.
AB  - A new way to make broadband polarizers on silicon-on-insulator (SOI) waveguides
      is proposed, analyzed and characterized. The characteristics of the eigenmodes in
      a shallowly-etched SOI ridge optical waveguide are analyzed by using a full
      vectorial finite-different method (FV-FDM) mode solver. The theoretical
      calculation shows that the loss of TE fundamental mode could be made very low
      while at the same time the TM fundamental mode has very large leakage loss, which
      is strongly dependent on the trench width. The leakage loss of the TM fundamental
      mode changes quasi-periodically as the trench width w(tr) varies. The formula of
      the period ?w(tr) is given. By utilizing the huge polarization dependent loss of
      this kind of waveguide, a compact and simple optical polarizer based on a
      straight waveguide was demonstrated. The polarizer is fabricated on a 700 nm
      thick SOI wafer and then characterized by using a free-space optical system. The
      measured extinction ratio is as high as 25 dB over a 100 nm wavelength range for
      a 1 mm-long polarizer.

PMID- 21197018
TI  - Initial ground-based thermospheric wind measurements using Doppler asymmetric
      spatial heterodyne spectroscopy (DASH).
AB  - We present the first thermospheric wind measurements using a Doppler Asymmetric
      Spatial Heterodyne (DASH) spectrometer and the oxygen red-line nightglow
      emission. The ground-based observations were made from Washington, DC and include
      simultaneous calibration measurements to track and correct instrument drifts.
      Even though the measurements were made under challenging thermal and light
      pollution conditions, they are of good quality with photon statistics
      uncertainties between about three and twenty-nine meters per second, depending on
      the nightglow intensity. The wind data are commensurate with a representative set
      of Millstone Hill Fabry-Perot wind measurements selected for similar geomagnetic
      and solar cycle conditions.

PMID- 21197019
TI  - Terahertz and far infrared spectroscopy of alanine-rich peptides having variable
      ellipticity.
AB  - Terahertz spectra of four alanine-rich peptides with known secondary structures
      were studied by terahertz time domain spectroscopy (THz-TDS) and by Fourier
      transform infrared spectroscopy (FTIR) using a synchrotron light source and a
      liquid-helium cooled bolometer. At ambient temperatures the usable bandwidth was
      restricted to 0.2-1.5 THz by the absorbance of water. The existence of a
      solvation shell around the peptide in solution was observed and its size
      estimated to be between 11 and 17 A. By cooling the peptide solution to 80 K in
      order to reduce the water absorbance the bandwidth was increased to 0.1-3.0 THz
      for both THz-TDS and FTIR. Spectra were consistent with monotonic absorbance of
      the peptide and the existence of a solid amorphous low density solvation shell.

PMID- 21197020
TI  - Control of pulse-to-pulse fluctuations in visible supercontinuum.
AB  - Long-pulse supercontinuum sources are initiated by modulation instability and
      consequently suffer from stochastic shot-to-shot variations of their spectral
      power density. In this paper, we provide a measurement of pulse-to-pulse
      fluctuations over the whole supercontinuum spectrum, and we show that their
      spectral dependence follows the group index curve of the fiber. Then, we
      demonstrate a significant reduction of supercontinuum pulse-to-pulse fluctuations
      in the visible by using a photonic crystal fiber with longitudinally tailored
      guidance properties. We finally show numerically that this new source would allow
      a significant improvement of the signal-to-noise ratio in fluorescence
      microscopy.

PMID- 21197021
TI  - On the correct modeling of semiconductor optical amplifier RIN and phase noise
      for optical phase shift keyed communication systems.
AB  - Phase modulation schemes are attracting much interest for use in ultra-fast
      optical communication systems because they are much less affected by fiber
      nonlinearities than conventional modulation formats. Semiconductor optical
      amplifiers (SOAs) can be used to amplify and process phase modulated signals.
      However, existing SOA nonlinear phase noise (NLPN) models are simplistic and,
      sometimes, inaccurate. It is, therefore, important to correctly model their
      behavior since NLPN is the main drawback in these applications. In this paper we
      show that a more accurate model can be used leading to simple nonlinear noise
      expressions at the SOA output of differential phase shift keying systems. To
      demonstrate the utility of this model, we have used it to calculate the optical
      signal to noise ratio penalties introduced by a power booster SOA and the first
      inline amplifier of a 40 Gb/s NRZ-DQPSK single channel link. The model parameters
      have been estimated from measurements taken of a commercial SOA.

PMID- 21197022
TI  - A scheme to polarize nuclear-spin of atoms by a sequence of short laser pulses:
      application to the muonium.
AB  - We theoretically show that a sequence of short laser pulses can efficiently
      polarize nuclear-spin of atoms/ions. This is a variant of optical pumping with an
      important difference that a sequence of short laser pulses is used instead of a
      continuous-wave laser. Such a replacement is particularly useful if the pumping
      wavelength is in the ultraviolet or vacuum-ultraviolet region where obtaining a
      continuous-wave light source with a sufficient intensity is very difficult.
      Because of the use of short laser pulses neither hyperfine transitions nor fine
      structure transitions are spectrally resolved, which is quite in contrast to the
      standard optical pumping scheme by a continuous-wave laser. As an example we
      apply the scheme to polarize the muonium (MU(+)e(-), lifetime 2.2 MUs), for which
      the pumping wavelength is 122 nm. From numerical solutions of a set of density
      matrix equations, we find that the use of only a single, two, and five pulses
      with a ps duration at the peak intensity of 2*10(8) W/cm(2) and a 5 ns time
      interval results in the degrees of spin-polarization of 33, 50, and 80 %,
      respectively, within the time scale of a few tens of ns.

PMID- 21197024
TI  - Formation of higher-band dark gap solitons in one dimensional waveguide arrays.
AB  - We experimentally observe the formation of spatial dark gap solitons in higher
      bands in one-dimensional waveguide arrays possessing a saturable defocusing
      nonlinearity. By using the prism-coupler scheme, pure Floquet-Bloch modes of
      higher bands are excited and dark gap solitons are formed due to the
      counteraction of normal diffraction and the defocusing nature of the photovoltaic
      nonlinearity. The modulation of refractive index induced by the soliton formation
      is demonstrated by the guidance of a low-power probe beam in the waveguide array
      sample. Additionally, the phase structure of dark solitons formed in the second
      band is discussed.

PMID- 21197023
TI  - Grazing angle Mach-Zehnder interferometer using reflective phase gratings and a
      polychromatic, un-collimated light source.
AB  - Normal incidence Talbot-Lau interferometers in x-ray applications have the
      drawbacks of low fringe visibility with polychromatic sources when the wave
      propagation distance is increased to achieve higher phase sensitivity, and when
      fabrication limits the attainable grating density. In contrast, reflective
      gratings illuminated at grazing angles have dramatically higher effective
      densities than their physical values. However, new designs are needed for far
      field interferometers using grazing angle geometry with incoherent light sources.
      We show that, with the appropriate design and choice of reflective phase
      gratings, there exist pairs of interfering pathways of exactly equal lengths
      independent of the incoming beam's incidence angle and wavelength. With a visible
      light grazing angle Mach-Zehnder interferometer, we show the conditions for
      achieving near ideal fringe visibility and demonstrate both absolute and
      differential phase-contrast imaging. We also describe the design parameters of an
      x-ray interferometer and key factors for its implementation.

PMID- 21197025
TI  - Holographic opto-fluidic microscopy.
AB  - Over the last decade microfluidics has created a versatile platform that has
      significantly advanced the ways in which micro-scale organisms and objects are
      controlled, processed and investigated, by improving the cost, compactness and
      throughput aspects of analysis. Microfluidics has also expanded into optics to
      create reconfigurable and flexible optical devices such as reconfigurable lenses,
      lasers, waveguides, switches, and on-chip microscopes. Here we present a new opto
      fluidic microscopy modality, i.e., Holographic Opto-fluidic Microscopy (HOM),
      based on lensless holographic imaging. This imaging modality complements the
      miniaturization provided by microfluidics and would allow the integration of
      microscopy into existing on-chip microfluidic devices with various
      functionalities. Our imaging modality utilizes partially coherent in-line
      holography and pixel super-resolution to create high-resolution amplitude and
      phase images of the objects flowing within micro-fluidic channels, which we
      demonstrate by imaging C. elegans, Giardia lamblia, and Mulberry pollen. HOM does
      not involve complicated fabrication processes or precise alignment, nor does it
      require a highly uniform flow of objects within microfluidic channels.

PMID- 21197026
TI  - Fourier factorization with complex polarization bases in the plane-wave expansion
      method applied to two-dimensional photonic crystals.
AB  - We demonstrate an enhancement of the plane wave expansion method treating two
      dimensional photonic crystals by applying Fourier factorization with generally
      elliptic polarization bases. By studying three examples of periodically arranged
      cylindrical elements, we compare our approach to the classical Ho method in which
      the permittivity function is simply expanded without changing coordinates, and to
      the normal vector method using a normal-tangential polarization transform. The
      compared calculations clearly show that our approach yields the best convergence
      properties owing to the complete continuity of our distribution of polarization
      bases. The presented methodology enables us to study more general systems such as
      periodic elements with an arbitrary cross-section or devices such as photonic
      crystal waveguides.

PMID- 21197027
TI  - Coupled-cavity surface-emitting lasers: spectral and polarization threshold
      characteristics and electrooptic switching.
AB  - We study spectral and polarization threshold characteristics of coupled-cavity
      Vertical-Surface-Emitting Lasers (CC-VCSEL) on the base of a simple matrix
      approach. We show that strong wavelength discrimination can be achieved in CC
      VCSELs by slightly detuning the cavities. However, polarization discrimination is
      not provided by the coupled-cavity design. We also consider the case of reverse
      biasing one of the cavities, i.e. using it as a modulator via linear and/or
      quadratic electrooptic effect. Such a CC-VCSEL can act as a voltage-controlled
      polarization or wavelength switching device that is decoupled from the laser
      design and can be optimized for high modulation speed. We also show that using QD
      stack instead of quantum wells in the top cavity would lead to significant
      reduction of the driving electrical field.

PMID- 21197028
TI  - Comparison between non-modulation four-sided and two-sided pyramid wavefront
      sensor.
AB  - Based on the diffraction theory the paper analyzes non-modulation Pyramid
      wavefront sensor (PWFS, namely, four-sided pyramid) and two-sided pyramid
      wavefront sensor (TSPWFS), and expresses the detected signals as a function of
      the measured wavefront. The expressions of the detected signals show that non
      modulation PWFS and TSPWFS hold the same properties of both slope and direct
      phase sensors. We compare both sensors working in slope and phase sensing by
      theory and numerical simulations. The results demonstrate that the performance of
      TSPWFS excels that of PWFS. Additionally, the influence of interference between
      adjacent pupils is discussed.

PMID- 21197029
TI  - Multiphoton fabrication of freeform polymer microstructures with gold nanorods.
AB  - In this study, three-dimensional (3D) polyacrylamide microstructures containing
      gold nanorods (AuNRs) were fabricated by two-photon polymerization (TPP) using
      Rose Bengal (RB) as the photoinitiator. To retain AuNRs in the 3D polymer
      microstructures, the laser wavelength was chosen for two-photon RB absorption for
      improved TPP efficiency, but not for enhancing the longitudinal plasmon resonance
      of AuNRs which may result in photothermal damage of AuNRs. After TPP processing,
      the laser wavelength was tuned for the longitudinal plasmon resonance and the
      laser power was increased to beyond the damage threshold of the AuNRs for
      reshaping the AuNRs into gold nanospheres. As a result, AuNRs in designated
      positions of the fabricated 3D microstructures can be achieved. Two-photon
      luminescence from the doped AuNRs can also act as contrast agent for the
      visualization of 3D polymer microstructures.

PMID- 21197030
TI  - Fabrication of glucose fiber sensor based on immobilized GOD technique for rapid
      measurement.
AB  - The concentration and pH value of the immobilized glucose oxidase (GOD) are
      critical parameters in a glucose sensor. In this study, we develop a glucose
      fiber sensor integrated with heterodyne interferometry to measure the phase
      difference arising from the chemical reaction between glucose and GOD. Our
      studies show that the response time and resolution of this sensor will be
      strongly affected by the pH and concentration properties of GOD. In addition, the
      results show good linearity between the calibration curve for the glucose
      solution and serum based sample. The response time of this sensor can be shorter
      than 3 seconds and best resolutions are 0.1 and 0.136 mg/dl for glucose solution
      and serum based sample, respectively.

PMID- 21197031
TI  - M2-factor of a stochastic electromagnetic beam in a Gaussian cavity.
AB  - With the help of a tensor method, an explicit expression for the M2-factor of a
      stochastic electromagnetic Gaussian Schell-model (EGSM) beam in a Gaussian cavity
      is derived. Evolution properties of the M2-factor of an EGSM beam in a Gaussian
      cavity are studied numerically in detail. It is found that the behavior of the M2
      factor of an EGSM beam in a Gaussian cavity is determined by the statistical
      properties of the source beam and the parameters of the cavity. Thermal lens
      effect induced changes of the M2-factor of an EGSM beam in a Gaussian cavity is
      also investigated. Our results will be useful in many applications, such as free
      space optical communications, laser radar system, optical trapping and optical
      imaging, where stochastic electromagnetic beams are required.

PMID- 21197032
TI  - High-power MIXSEL: an integrated ultrafast semiconductor laser with 6.4 W average
      power.
AB  - High-power ultrafast lasers are important for numerous industrial and scientific
      applications. Current multi-watt systems, however, are based on relatively
      complex laser concepts, for example using additional intracavity elements for
      pulse formation. Moving towards a higher level of integration would reduce
      complexity, packaging, and manufacturing cost, which are important requirements
      for mass production. Semiconductor lasers are well established for such
      applications, and optically-pumped vertical external cavity surface emitting
      lasers (VECSELs) are most promising for higher power applications, generating the
      highest power in fundamental transverse mode (>20 W) to date. Ultrashort pulses
      have been demonstrated using passive modelocking with a semiconductor saturable
      absorber mirror (SESAM), achieving for example 2.1-W average power, sub-100-fs
      pulse duration, and 50-GHz pulse repetition rate. Previously the integration of
      both the gain and absorber elements into a single wafer was demonstrated with the
      MIXSEL (modelocked integrated external-cavity surface emitting laser) but with
      limited average output power (<200 mW). We have demonstrated the power scaling
      concept of the MIXSEL using optimized quantum dot saturable absorbers in an
      antiresonant structure design combined with an improved thermal management by
      wafer removal and mounting of the 8-um thick MIXSEL structure directly onto a CVD
      diamond heat spreader. The simple straight cavity with only two components has
      generated 28-ps pulses at 2.5-GHz repetition rate and an average output power of
      6.4 W, which is higher than for any other modelocked semiconductor laser.

PMID- 21197033
TI  - Light absorption and emission in nanowire array solar cells.
AB  - Inorganic nanowires are under intense research for large scale solar power
      generation intended to ultimately contribute a substantial fraction to the
      overall power mix. Their unique feature is to allow different pathways for the
      light absorption and carrier transport. In this publication we investigate the
      properties of a nanowire array acting as a photonic device governed by wave
      optical phenomena. We solve the Maxwell equations and calculate the light
      absorption efficiency for the AM1.5d spectrum and give recommendations on the
      design. Due to concentration of the incident sunlight at a microscopic level the
      absorptivity of nanowire solar cells can exceed the absorptivity of an equal
      amount of material used in thin-film devices. We compute the local density of
      photon states to assess the effect of emission enhancement, which influences the
      radiative lifetime of excess carriers. This allows us to compute the efficiency
      limit within the framework of detailed balance. The efficiency is highly
      sensitive with respect to the diameter and distance of the nanowires. Designs
      featuring nanowires below a certain diameter will intrinsically feature low short
      circuit current that cannot be compensated even by increasing the nanowire
      density. Optimum efficiency is not achieved in densely packed arrays, in fact
      spacing the nanowires further apart (simultaneously decreasing the material use)
      can even improve efficiency in certain scenarios. We observe absorption
      enhancement reducing the material use. In terms of carrier generation per
      material use, nanowire devices can outperform thin-film devices by far.

PMID- 21197034
TI  - Polarity-variable birefringence on hyperlens structure.
AB  - A variable birefringence effect has been observed with 1D PMMA surface gratings
      on a gold film substrate. By changing the operation wavelength on the Au film,
      the birefringence value Deltan(eff) changes from positive to negative. The result
      verified that this uniaxial crystal-like plasmonic surface gratings showed good
      superlensing effect at 515 nm when PMMA width:Air width=1:1 where the absolute
      value of Deltan(eff) is relatively large.

PMID- 21197035
TI  - Phase optimization of dispersive mirrors based on floating constants.
AB  - A novel floating constants phase-optimization technique is developed and applied
      to the design of dispersive mirrors. This technique reduces the dispersive
      mirror's sensitivity to layer thickness errors. To demonstrate the significant
      improvement in design stability, we theoretically and experimentally compare our
      new phase-optimization approach to the conventional one. The fabricated
      dispersive mirror has a reflectivity of >99.99% and provides an accurate
      dispersion control over a bandwidth of around 60 nm.

PMID- 21197036
TI  - Three dimensional nanoparticle trapping enhanced by surface plasmon resonance.
AB  - We demonstrate a three dimensional nanoparticle trapping approach aided by the
      surface plasmon resonance of metallic nanostructures. The localized surface
      plasmon resonance effect provides strong electromagnetic field enhancement, which
      enables confinement of nanoparticles in the three-dimensional space. Numerical
      simulations indicate that the plasmonic structure provides approximately two
      orders of magnitude stronger optical forces for trapping nanoparticles, compared
      with that without nanostructures. The study of thermal effect of the plasmonic
      structure shows that the impact of the thermal force is significant, which may
      determine the outcome of the nanoparticle trapping.

PMID- 21197037
TI  - Loss engineered slow light waveguides.
AB  - Slow light devices such as photonic crystal waveguides (PhCW) and coupled
      resonator optical waveguides (CROW) have much promise for optical signal
      processing applications and a number of successful demonstrations underpinning
      this promise have already been made. Most of these applications are limited by
      propagation losses, especially for higher group indices. These losses are caused
      by technological imperfections ("extrinsic loss") that cause scattering of light
      from the waveguide mode. The relationship between this loss and the group
      velocity is complex and until now has not been fully understood. Here, we present
      a comprehensive explanation of the extrinsic loss mechanisms in PhC waveguides
      and address some misconceptions surrounding loss and slow light that have arisen
      in recent years. We develop a theoretical model that accurately describes the
      loss spectra of PhC waveguides. One of the key insights of the model is that the
      entire hole contributes coherently to the scattering process, in contrast to
      previous models that added up the scattering from short sections incoherently. As
      a result, we have already realised waveguides with significantly lower losses
      than comparable photonic crystal waveguides as well as achieving propagation
      losses, in units of loss per unit time (dB/ns) that are even lower than those of
      state-of-the-art coupled resonator optical waveguides based on silicon photonic
      wires. The model will enable more advanced designs with further loss reduction
      within existing technological constraints.

PMID- 21197038
TI  - Numerical investigation on polarization characteristics of coherent enhanced
      backscattering using SLPSTD.
AB  - We investigate the polarization characteristics of coherent enhanced
      backscattering (EBS) using the pseudo-spectral time domain method implemented on
      staggered grid and local Fourier basis (SLPSTD) [Opt. Express 18, 9236 (2010)].
      The studies are focused on Mie scatterers with findings profound to the
      understanding of polarization evolution in the scattering process. For linear
      polarization studies, the low-order scattering component of EBS is azimuthally
      anisotropic. A relationship between the degree of anisotropy and the photon's
      penetration depth is established to characterize the depolarization progress. For
      circular polarization, exact numerical solutions disclose the origin of
      polarization memory effect and the helicity-flipping phenomenon. The region
      responsible for helicity-flipping is identified. Our numerical technique can be
      potentially applied to subsurface imaging that explores polarization memory
      effect.

PMID- 21197039
TI  - Generation and tight focusing of hybridly polarized vector beams.
AB  - We propose and experimentally demonstrate the generation of hybridly polarized
      beams by transmitting radially polarized light through a wave plate. We show that
      such beams span a closed circle on the surface of the Poincare sphere whose
      center coincides with the center of the sphere. In addition we numerically
      investigate the field and energy density distribution across the focal plane of a
      high NA lens illuminated by such a hybrid beam. The results show an interesting
      polarization distribution with 3D orientation and space variant ellipticity. This
      kind of polarization distributions may be used for a variety of applications,
      e.g. particle orientation analysis, microscopy and in atomic systems.

PMID- 21197040
TI  - Three dimensional optical manipulation and structural imaging of soft materials
      by use of laser tweezers and multimodal nonlinear microscopy.
AB  - We develop an integrated system of holographic optical trapping and multimodal
      nonlinear microscopy and perform simultaneous three-dimensional optical
      manipulation and non-invasive structural imaging of composite soft-matter
      systems. We combine different nonlinear microscopy techniques such as coherent
      anti-Stokes Raman scattering, multi-photon excitation fluorescence and multi
      harmonic generation, and use them for visualization of long-range molecular order
      in soft materials by means of their polarized excitation and detection. The
      combined system enables us to accomplish manipulation in composite soft materials
      such as colloidal inclusions in liquid crystals as well as imaging of each
      separate constituents of the composite material in different nonlinear optical
      modalities. We also demonstrate optical generation and control of topological
      defects and simultaneous reconstruction of their three-dimensional long-range
      molecular orientational patterns from the nonlinear optical images.

PMID- 21197041
TI  - Difference frequency generation spectrometer for simultaneous multispecies
      detection.
AB  - A difference-frequency generation based spectrometer system for simultaneous
      ultra-sensitive measurements of formaldehyde (CH2O) and Methane (CH4) is
      presented. A new multiplexing approach using collinear quasi-phase-matching in a
      single grating period of periodically poled lithium niobate (PPLN) is discussed
      and demonstrated for two pairs of pump and signal lasers to generate mid-infrared
      frequencies at 2831.64 cm(-1) and 2916.32 cm(-1), respectively. The corresponding
      absorption signals are discriminated by modulating the DFB diode lasers at
      modulation frequencies of 40 kHz and 50 kHz, respectively, and using a computer
      based modulation and de-modulation scheme. In addition, simultaneous measurements
      of CH2O, CH4 and H2O are demonstrated utilizing both collinear and non-collinear
      quasi-phase-matching.

PMID- 21197042
TI  - Scattering of pulsed plane wave from a symmetrical groove doublet configuration.
AB  - We have provided theoretical study on the spectral and temporal properties of the
      scattering of pulsed plane wave from a symmetrical groove doublet configuration.
      Based on the numerical calculation results, we show that the spectrum and the
      waveform of the scattered field are sensitive to the shape of the rectangular
      grooves when the grooves are deep enough. In both spectral and temporal domain, a
      damped oscillatory behavior occurs when the groove spacing increases.
      Furthermore, the spectral and temporal dependences of the angular distribution
      are consisted of interference-like fringe patterns. These patterns are sensitive
      to the size of the groove width and spacing rather than the groove shape when the
      depth is small enough. Our study takes the analysis of pulse scattering by finite
      grooves a step further on the theoretical side, and offers opportunities for the
      control of spectral and temporal properties of pulsed scattered wave in low
      frequency regime such as THz and microwave domain.

PMID- 21197043
TI  - Self-focusing and defocusing of twisted light in non-linear media.
AB  - We study the self-focusing and defocusing of a light beam carrying angular
      momentum (called twisted light) propa- gating in a nonlinear medium. We derive a
      differential equation for the beam width parameter f as a function of the
      propagation distance, angular frequency, beam waist and intensity of the beam.
      The method is based on the Wentzel-Kramers-Brillouin and the paraxial
      approximations. Analytical expressions for f are obtained, analyzed and
      illustrated for typical experimental situations.

PMID- 21197044
TI  - Multi-wavelength laser from dye-doped cholesteric polymer films.
AB  - A multi-wavelength laser is demonstrated using a dye-doped cholesteric polymer
      film whose reflection bandwidth is broadened with several oscillations. Due to
      the abrupt change of the density of state between oscillation peak and valley,
      each oscillation functions as a photonic band gap for generating a laser
      wavelength under the excitation of a pumping laser. As a result, a multiple
      wavelength laser is generated. Results indicate that the dye-doped cholesteric
      liquid crystal polymer film is a good candidate for fabricating broadband lasers
      such as white light lasers. Potential applications include experimental testing
      of laser materials, identification markers, information displays, and inertial
      confinement laser fusion.

PMID- 21197045
TI  - Monolithic integration of erbium-doped amplifiers with silicon-on-insulator
      waveguides.
AB  - Monolithic integration of Al2O3:Er3+ amplifier technology with passive silicon-on
      insulator waveguides is demonstrated. A signal enhancement of >7 dB at 1533 nm
      wavelength is obtained. The straightforward wafer-scale fabrication process,
      which includes reactive co-sputtering and subsequent reactive ion etching, allows
      for parallel integration of multiple amplifier and laser sections with silicon or
      other photonic circuits on a chip.

PMID- 21197046
TI  - Nanoimprinted photonic crystal color filters for solar-powered reflective
      displays.
AB  - A novel concept for reflective displays that uses two-dimensional photonic
      crystals with subwavelength gratings is introduced. A solar-powered reflective
      display with photonic crystal color filters was analyzed by a theoretical
      approach. We fabricated the photonic crystal color filters on a glass substrate
      by using low-cost nanoimprint lithography and multi-scan excimer laser annealing
      to produce RGB color filters through a single patterning process. The theoretical
      and experimental results show that the color filters have high reflectance and
      angular tolerance, which was qualitatively confirmed by chromaticity coordination
      analysis.

PMID- 21197047
TI  - Adaptive conversion of multimode beam to near-diffraction-limited flattop beam
      based on dual-phase-only liquid-crystal spatial light modulators.
AB  - We propose and demonstrate the adaptive conversion of a multimode beam into a
      near-diffraction-limited flattop beam in the near field based on a combination of
      dual-phase-only liquid-crystal spatial light modulators (LC-SLMs) and the
      stochastic parallel gradient descent (SPGD) algorithm. One phase-only LC-SLM
      redistributes the intensity of the multimode beam, and the other compensates the
      wavefront of the output beam. The SPGD algorithm adaptively optimizes the phase
      distributions of dual-phase-only LC-SLMs to reduce the variance between the
      actual beam shape and the target beam shape. The experimental results on a fiber
      multimode beam show that the system is capable of adaptively creating square and
      rectangle flattop beams with desired parameters. Beam quality can be greatly
      improved by this system. The power in the main lobe of the far-field spot is
      about 4 times larger than that of the input multimode beam.

PMID- 21197048
TI  - Finite-difference analysis of plasmon-induced forces of metal nano-clusters by
      the Lorentz force formulation.
AB  - We analyze light-induced forces on metal nano-spheres by using the three
      dimensional finite-difference time-domain method with the Lorentz force
      formulation. Convergent analysis of the force on metal nano-particle clusters has
      been achieved by integrating the Lorentz and the Coulomb forces over the volume
      of the metal particles. Comparison to the Mie theory of radiation pressure on
      metal spheres under a plane wave illumination has verified rigorously the
      accuracy of the numerical method. We also analyze separate two metal spheres in
      close proximity and the results of the induced forces are compared to those in
      previous publications. The present method allows analysis of forces on various
      irregular structures; we apply the method to touching metal spheres, forming a
      simple cluster with a slight deformation at the contact point, to analyze the
      forces induced by the plasmonic resonance of the clusters. We show that the
      fundamental resonance modes, which newly appear in an infrared range when spheres
      are touching, exhibit strong binding forces within the clusters. Based on the
      numerical analyses we identify the resonance modes and evaluate quantitatively
      the infrared-induced forces on metal nano-sphere clusters.

PMID- 21197049
TI  - Metamaterial-based gradient index lens with strong focusing in the THz frequency
      range.
AB  - The development of innovative terahertz (THz) imaging systems has recently moved
      in the focus of scientific efforts due to the ability to screen substances
      through textiles or plastics. The invention of THz imaging systems with high
      spatial resolution is of increasing interest for applications in the realms of
      quality control, spectroscopy in dusty environment and security inspections. To
      realize compact THz imaging systems with high spatial resolution it is necessary
      to develop lenses of minimized thickness that still allow one to focus THz
      radiation to small spot diameters with low optical aberrations. In addition, it
      would be desirable if the lenses offered adaptive control of their optical
      properties to optimize the performance of the imaging systems in the context of
      different applications. Here we present the design, fabrication and the
      measurement of the optical properties of spectrally broadband metamaterial-based
      gradient index (GRIN) lenses that allow one to focus THz radiation to a spot
      diameter of approximately one wavelength. Due to the subwavelength thickness and
      the high focusing strength the presented GRIN lenses are an important step
      towards compact THz imaging systems with high spatial resolution. Furthermore,
      the results open the path to a new class of adaptive THz optics by extension of
      the concept to tunable metamaterials.

PMID- 21197050
TI  - 21 Gb/s after 100 km OFDM long-reach PON transmission using a cost-effective
      electro-absorption modulator.
AB  - We experimentally demonstrate a superior performance of 2.1-Tb/s.km OFDM signal
      transmission over 100-km long-reach PONs. While the bandwidth of a 100-km SMF
      transmission system is limited to 4.3 GHz due to positive chirp, we successfully
      achieve spectrally-efficient 21-Gb/s signaling by using a cost-effective and low
      chirp EAM, and adopting the 128-QAM format and adaptive subcarrier pre-emphasis.

PMID- 21197051
TI  - Polarization selective, graded-reflectivity resonance filter, using a space
      varying guided-mode resonance structure.
AB  - We designed, fabricated, and tested, polarization selective, graded-reflectivity
      resonant filters; based on a radial-gradient spatially-distributed, guided-mode
      resonance device architecture. The demonstrated filters have polarized spectral
      resonance responses, distributed across their aperture extent, in the range
      between 1535 nm and 1540 nm wavelengths. Spectral sensitivity was observed on
      device tests, for wavelength changes as low as 0.2 nm. Using multiple
      lithographic exposures and biasing exposure methods, the devices were engineered
      to have a sub-aperture region, with no hard boundaries or diffraction anomalies.

PMID- 21197052
TI  - Patterned color liquid crystal polymer polarizers.
AB  - We demonstrate patterned polarizers for visible wavelengths using dichroic dye in
      a liquid crystal polymer (LCP) host. Contact lithography is used to pattern a
      thin alignment layer, which subsequently transfers the pattern to the LCP. A gray
      dichroic dye mixture for the visible spectrum is optimized and implemented along
      with LCP to fabricate this polarizer. A peak extinction ratio of 41 was measured
      at a 633 nm wavelength, while simultaneously showing patterns as small as 3 MUm.
      Finally, multi layer films are demonstrated by fabricating a two layer patterned
      circular polarizer consisting of a quarter-wave retarder and a color polarizer.
      Our process has applications in three-dimensional displays, interferometry,
      optical storage, and polarimeters.

PMID- 21197053
TI  - Adaptive imaging system with spatial light modulator for robust shape measurement
      of partially specular objects.
AB  - In imaging systems, when specular surfaces responding sensitively to varying
      illumination conditions are imaged on groups of CCD pixels using imaging optics,
      the obtained image usually suffers from pixel saturation, resulting in smearing
      or blooming phenomena. These problems are then serious obstacles when applying
      structured light-based optical profiling methods to the shape measurement of
      general objects with partially specular surfaces. Therefore, this paper combines
      a phase-based profiling system with an with an adaptive spatial light modulator
      in the imaging part for measuring the three-dimensional shapes of objects with an
      advanced dynamic range. The use of a spatial light modulator in front of a CCD
      camera prevents the image sensor from being saturated, as the pixel transmittance
      is controlled by monitoring the input images and providing modulator feedback
      signals over time and space. When using the proposed system, since the projected
      fringes are effectively imaged on the CCD without any pixel saturation, phase
      information according to the object's shape can be correctly extracted from non
      saturated images. The configuration of the proposed system and transmittance
      control scheme are explained in detail, plus the performance is verified through
      a series of experiments, in which phase information was successfully extracted
      from areas that are not normally measurable due to saturation. Based on the
      results, the proposed shape measurement system showed a more advanced adaptive
      dynamic range when compared with a conventional system.

PMID- 21197054
TI  - Theoretical investigation of silicon MOS-type plasmonic slot waveguide based MZI
      modulators.
AB  - In this paper, a Mach-Zehnder silicon nanoplasmonic electro-optic modulator is
      proposed and theoretically analyzed. It is composed of horizontal metal-SiO2-Si
      metal plasmonic slot waveguides for phase shifting and ultracompact V-shape
      splitter/combiner to link the plasmonic slot waveguides and the conventional Si
      dielectric waveguides. The proposed modulator can be directly integrated into
      existing Si electronic photonic integrated circuits (EPICs) and be fabricated
      using standard Si complementary metal-oxide-semiconductor (CMOS) technology. The
      modulator's parameters are optimized through systematic 2-dimensional numerical
      simulations. For a modulator with 3-um-long Ag-SiO2(2 nm)-Si(50 nm)-Ag phase
      shifter and 0.35-um-long splitter/combiner operating at 1.55-um wavelength,
      simulation shows an insertion loss of ~-8 dB, an extinction ratio of ~7.3 dB -
      with a switching voltage of ~5.6 V, and a bandwidth of ~500 GHz. A possible
      approach to reduce the switching voltage is addressed.

PMID- 21197055
TI  - The modulation function and realizing method of holographic functional screen.
AB  - The modulation function of holographic functional screen (HFS) in the real-time,
      large-size full-color (RLF), three-dimensional (3D) display system is derived
      from angular spectrum analysis. The directional laser speckle (DLS) method to
      realize the HFS is proposed. A HFS by the DLS method was fabricated and used in
      the experiment. Experimental results show that the HFS is valid in the RLF 3D
      display, and that the derived modulation function is valuable for the design of
      the HFS. The research results are important to realize the RLF 3D display system
      which will find many applications such as holographic video.

PMID- 21197056
TI  - Coherent addition of fiber-amplified ultrashort laser pulses.
AB  - We report on a novel approach of performance scaling of ultra-fast lasers by
      means of coherent combination. Pulses from a single mode-locked laser are
      distributed to a number of spatially separated fiber amplifiers and coherently
      combined after amplification. Splitting and combination is achieved by
      polarization cubes, i.e. the approach bases on polarization combining. A Hansch
      Couillaud detector measures the polarization state at the output. The error
      signal (deviation from linear polarization) is used to stabilize the
      synchronization of different channels. In a proof-of-principle experiment the
      combination of two femtosecond fiber-based CPA systems is presented. A combining
      efficiency as high as 97% has been achieved. The technique offers a unique
      scaling potential and can be applied to all ultrafast amplification schemes
      independent of the architecture of the gain medium.

PMID- 21197057
TI  - Spot size characterization of focused non-Gaussian X-ray laser beams.
AB  - We present a new technique for the characterization of non-Gaussian laser beams
      which cannot be described by an analytical formula. As a generalization of the
      beam spot area we apply and refine the definition of so called effective area
      (A(eff)) [1] in order to avoid using the full-width at half maximum (FWHM)
      parameter which is inappropriate for non-Gaussian beams. Furthermore, we
      demonstrate a practical utilization of our technique for a femtosecond soft X-ray
      free-electron laser. The ablative imprints in poly(methyl methacrylate) - PMMA
      and amorphous carbon (a-C) are used to characterize the spatial beam profile and
      to determine the effective area. Two procedures of the effective area
      determination are presented in this work. An F-scan method, newly developed in
      this paper, appears to be a good candidate for the spatial beam diagnostics
      applicable to lasers of various kinds.

PMID- 21197058
TI  - Azimuthons in weakly nonlinear waveguides of different symmetries.
AB  - We show that weakly guiding nonlinear waveguides support stable propagation of
      rotating spatial solitons (azimuthons). We investigate the role of waveguide
      symmetry on the soliton rotation. We find that azimuthons in circular waveguides
      always rotate rigidly during propagation and the analytically predicted rotation
      frequency is in excellent agreement with numerical simulations. On the other
      hand, azimuthons in square waveguides may experience spatial deformation during
      propagation. Moreover, we show that there is a critical value for the modulation
      depth of azimuthons above which solitons just wobble back and forth, and below
      which they rotate continuously. We explain these dynamics using the concept of
      energy difference between different orientations of the azimuthon.

PMID- 21197059
TI  - A new method for locking the signal-field phase difference in a type-II optical
      parametric oscillator above threshold.
AB  - We propose and demonstrate a new method for phaselocking the signal fields
      emitted above threshold by a nondegenerate, type-II optical parametric oscillator
      (OPO). This method is based on the observation that amplitude modulation of the
      pump beam produces a related modulation of the frequency difference of the OPO
      signals via the temperature-tuning of the index of refraction in the nonlinear
      crystal. We successfully use pump modulation as a correction for phase-difference
      locking of the OPO signals and observe a 1 kHz beat note stable over more than 10
      s, both figures solely limited by the measurement time. This method eliminates
      the need for applying electronic phase-correction signals directly to the
      nonlinear crystal which caused crystal damage in a previous phaselocking
      technique.

PMID- 21197060
TI  - Scalar generalized nonlinear Schrodinger equation-quantified continuum generation
      in an all-normal dispersion photonic crystal fiber for broadband coherent optical
      sources.
AB  - We quantitatively predict the observed continuum-like spectral broadening in a 90
      mm weakly birefringent all-normal dispersion-flattened photonic crystal fiber
      pumped by 1041-nm 229-fs 76-MHz pulses from a solid-state Yb:KYW laser. The well
      characterized continuum pulses span a bandwidth of up to 300 nm around the laser
      wavelength, allowing high spectral power density pulse shaping useful for various
      coherent control applications. We also identify the nonlinear polarization effect
      that limits the bandwidth of these continuum pulses, and therefore report the
      path toward a series of attractive alternative broadband coherent optical
      sources.

PMID- 21197061
TI  - Experimental demonstration of bandwidth enhancement based on two-pump wavelength
      conversion in a silicon waveguide.
AB  - We experimentally demonstrate the bandwidth enhancement of wavelength conversion
      in a silicon waveguide based on four-wave mixing (FWM) with two continuous-wave
      pumps. Our measurement results show 25% bandwidth improvement from 29.8 nm to
      37.4 nm in a 17-mm-long silicon waveguide with a pump spacing of 14.9 nm as
      compared to a single-pump FWM. The experimental results are verified by
      theoretical calculations and >40% bandwidth enhancement is predicted by further
      wavelength separation of the two pumps.

PMID- 21197062
TI  - Plasmon-induced optical switching of electrical conductivity in porous anodic
      aluminum oxide films encapsulated with silver nanoparticle arrays.
AB  - We report on plasmon induced optical switching of electrical conductivity in two
      dimensional (2D) arrays of silver (Ag) nanoparticles encapsulated inside
      nanochannels of porous anodic aluminum oxide (AAO) films. The reversible
      switching of photoconductivity greatly enhanced by an array of closely spaced Ag
      nanoparticles which are isolated from each other and from the ambient by thin
      aluminum oxide barrier layers are attributed to the improved electron transport
      due to the localized surface plasmon resonance and coupling among Ag
      nanoparticles. The photoconductivity is proportional to the power, and strongly
      dependent on the wavelength of light illumination. With Ag nanoparticles being
      isolated from the ambient environments by a thin layer of aluminum oxide barrier
      layer of controlled thickness in nanometers to tens of nanometers, deterioration
      of silver nanoparticles caused by environments is minimized. The
      electrochemically fabricated nanostructured Ag/AAO is inexpensive and promising
      for applications to integrated plasmonic circuits and sensors.

PMID- 21197063
TI  - Dispersion control with reflection grisms of an ultra-broadband spectrum
      approaching a full octave.
AB  - We report the design, implementation, and characterization of a grism-pair
      stretcher in a near-infrared noncollinear optical parametric chirped-pulse
      amplifier (OPCPA) that is capable of controlling a bandwidth of 440 nm. Our
      dynamic dispersion control scheme relies on the grism stretcher working in
      conjunction with an acousto-optic programmable dispersive filter (Dazzler) to
      jointly compensate large amount of material dispersion. A spectral interference
      technique is used to characterize the spectral phase of the grism stretcher. This
      ultra-broadband device opens up the way to generate sub-2-cycle laser pulses.

PMID- 21197064
TI  - Millijoule-level Yb-doped photonic crystal fiber laser passively Q-switched with
      AlGaInAs quantum wells.
AB  - We report on a millijoule-level Yb-doped photonic crystal fiber (PCF) laser
      passively Q-switched with AlGaInAs quantum wells (QWs). Three types of AlGaInAs
      devices with different QW numbers are fabricated to investigate the performance.
      With 50 groups of three AlGaInAs QWs as a saturable absorber (SA), the PCF laser
      generates an average power of 7.1 W with a pulse repetition rate of 6.5 kHz at a
      pump power of 16 W, corresponding to the pulse energy of 1.1 mJ. The maximum peak
      power is up to 110 kW.

PMID- 21197065
TI  - Theory of negative refraction in periodic stratified metamaterials.
AB  - We present a general theory of negative refraction in periodic stratified
      heterostructures with an arbitrary number of homogeneous, isotropic, nonmagnetic
      layers in a unit cell. With a 4*4-matrix technique, we derive analytic
      expressions for the normal modes of such a heterostructure slab, introduce the
      average refraction angles of the energy flow and wavevector for the TE- and TM
      polarized plane waves falling obliquely on the slab, and derive expressions for
      the reflectivity and transmissivity of the whole slab. For a specific case, in
      which all layers in a unit cell are much thinner than the wavelength of light, we
      obtain approximate simple formulae for the effective refraction angles. Using the
      example of a semiconductor heterostructure slab with two layers in a unit cell,
      we demonstrate that ultrathin layers are preferable for metamaterial applications
      because they enable higher transmissivity within the frequency band of negative
      refraction. Our theory can be used to study the optical properties of any
      stratified metamaterial, irrespective of whether semiconductors or metals are
      employed for fabricating its various layers, because it includes absorption
      within each layer.

PMID- 21197066
TI  - Photonic crystal slab sensor with enhanced surface area.
AB  - In this work, we demonstrate improved molecular detection sensitivity for silicon
      slab photonic crystal cavities by introducing multiple-hole defects (MHDs), which
      increase the surface area available for label-free detection without degrading
      the quality factor. Compared to photonic crystals with L3 defects, adding MHDs
      into photonic crystal cavities enabled a 44% increase in detection sensitivity
      towards small refractive index perturbations due to surface monolayer attachment
      of a small aminosilane molecule. Also, photonic crystals with MHDs exhibited 18%
      higher detection sensitivity for bulk refractive index changes.

PMID- 21197067
TI  - Thermal blinding of gated detectors in quantum cryptography.
AB  - It has previously been shown that the gated detectors of two commercially
      available quantum key distribution (QKD) systems are blindable and controllable
      by an eavesdropper using continuous-wave illumination and short bright trigger
      pulses, manipulating voltages in the circuit [Nat. Photonics 4, 686 (2010)]. This
      allows for an attack eavesdropping the full raw and secret key without increasing
      the quantum bit error rate (QBER). Here we show how thermal effects in detectors
      under bright illumination can lead to the same outcome. We demonstrate that the
      detectors in a commercial QKD system Clavis2 can be blinded by heating the
      avalanche photo diodes (APDs) using bright illumination, so-called thermal
      blinding. Further, the detectors can be triggered using short bright pulses once
      they are blind. For systems with pauses between packet transmission such as the
      plug-and-play systems, thermal inertia enables Eve to apply the bright blinding
      illumination before eavesdropping, making her more difficult to catch.

PMID- 21197068
TI  - Recent Development of Bifunctional Small Molecules to Study Metal-Amyloid-beta
      Species in Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is a multifactorial neurodegenerative disease related to
      the deposition of aggregated amyloid-beta (Abeta) peptides in the brain. It has
      been proposed that metal ion dyshomeostasis and miscompartmentalization
      contribute to AD progression, especially as metal ions (e.g., Cu(II) and Zn(II))
      found in Abeta plaques of the diseased brain can bind to Abeta and be linked to
      aggregation and neurotoxicity. The role of metal ions in AD pathogenesis,
      however, is uncertain. To accelerate understanding in this area and contribute to
      therapeutic development, recent efforts to devise suitable chemical reagents that
      can target metal ions associated with Abeta have been made using rational
      structure-based design that combines two functions (metal chelation and Abeta
      interaction) in the same molecule. This paper presents bifunctional compounds
      developed by two different design strategies (linkage or incorporation) and
      discusses progress in their applications as chemical tools and/or potential
      therapeutics.

PMID- 21197070
TI  - A newly developed variable stiffness duodenoscope for diagnostic and therapeutic
      endoscopic retrograde cholangiopancreatography.
AB  - The aim of this study is to evaluate a prototype variable stiffness duodenoscope
      (VSD) for diagnostic and therapeutic ERCP in comparison with standard
      duodenoscopes. We performed retrospective analysis on the success rate of
      intubation of the second duodenum, overall procedural success rate, and
      comparative frequency of the necessity to change duodenoscopes from standard JF
      260V and TJF 260V or to change stiffness using the VSD. A total of 213
      nonconsecutive procedures in 196 patients with pancreaticobiliary diseases. There
      was no statistically significant difference in endoscope intubation rate or
      technical success rate between the different duodenoscopes. In one patient with
      severe duodenal stenosis, the VSD using the moderately stiff mode allowed the
      major papilla to be reached when the TJF-260V endoscope could not. There were no
      serious procedure-related adverse events. In conclusion, while the VSD performed
      well, the present models do not appear to offer obvious advantages over the
      standard duodenoscopes for routine diagnostic and therapeutic ERCP. Prospective
      studies may be warranted to identify those patients who would benefit from this
      new technology.

PMID- 21197069
TI  - Complete Mitochondrial Genome Sequence of Acrida cinerea (Acrididae: Orthoptera)
      and Comparative Analysis of Mitochondrial Genomes in Orthoptera.
AB  - The complete 15,599-bp mitogenome of Acrida cinerea was determined and compared
      with that of the other 20 orthopterans. It displays characteristic gene content,
      genome organization, nucleotide composition, and codon usage found in other
      Caelifera mitogenomes. Comparison of 21 orthopteran sequences revealed that the
      tRNAs encoded by the H-strand appear more conserved than those by the L-stand.
      All tRNAs form the typical clover-leaf structure except trnS (agn), and most of
      the size variation among tRNAs stemmed from the length variation in the arm and
      loop of TPsiC and the loop of DHU. The derived secondary structure models of the
      rrnS and rrnL from 21 orthoptera species closely resemble those from other
      insects on CRW except a considerably enlarged loop of helix 1399 of rrnS in
      Caelifera, which is a potentially autapomorphy of Caelifera. In the A+T-rich
      region, tandem repeats are not only conserved in the closely related mitogenome
      but also share some conserved motifs in the same subfamily. A stem-loop
      structure, 16 bp or longer, is likely to be involved in replication initiation in
      Caelifera and Grylloidea. A long T-stretch (>17 bp) with conserved stem-loop
      structure next to rrnS on the H-strand, bounded by a purine at either end, exists
      in the three species from Tettigoniidae.

PMID- 21197071
TI  - Double transseptal puncture for catheter ablation of atrial fibrillation: safety
      of the technique and its use in the outpatient setting.
AB  - Introduction. For pulmonary vein isolation in patients with atrial fibrillation
      (AF), some centers use the double transseptal puncture technique for catheter
      access in order to facilitate catheter manipulation within the left atrium.
      However, no safety data has so far been published using this approach. Method.
      269 ablation procedures were performed in 243 patients (mean age 56.6 +/- 9.3
      years, 75% men) using the double transseptal puncture for catheter access in all
      cases. Patients were considered for ablation of paroxysmal (80%), persistent
      (19%), and permanent (1%) AF. 230 procedures were performed on an outpatient
      basis (85.5%), and 26 were repeat procedures (9.7%). Results. The double
      transseptal puncture catheter access was successfully achieved in all patients.
      The procedural success with the endpoint of pulmonary vein isolation was reached
      in 255 procedures (95%). A total of 1048 out of 1062 pulmonary veins (99%) were
      successfully isolated. Major complications occurred in eight patients (3.0%). Of
      these, seven patients (2.6%) had pericardial effusion requiring percutaneous
      drainage, and one patient (0.4%) suffered a minor reversible stroke. One patient
      (0.4%) had a minor air embolism with transient symptoms. Conclusion. The double
      transseptal puncture catheterization technique allows easy catheter manipulation
      within the left atrium to reach the goal of acute procedural success in AF
      ablation. Procedure-related complications are rare, and the technique can be used
      safely for AF ablation in the outpatient setting.

PMID- 21197072
TI  - Cryopreservation of parathyroid glands.
AB  - The risk of permanent hypoparathyroidism following thyroid and parathyroid
      surgery is around 1% in the hands of experienced endocrine surgeons. Although
      this complication is rare, rendering a patient permanently aparathyroid has
      significant consequences on the health and quality of life of the patient.
      Immediate autotransplantation of parathyroid glands that are injured or
      unintentionally removed offers the best possibility of graft viability and
      functionality. However, since the majority of cases of hypoparathyroidism are
      transient, immediate autotransplantation can complicate postoperative
      surveillance in certain patients, especially those with primary
      hyperparathyroidism. Cryopreservation of parathyroid tissue is an alternate
      technique that was developed to treat patients with permanent hypoparathyroidism.
      This method allows for parathyroid tissue to be stored and then autotransplanted
      in a delayed fashion once permanent hypoparathyroidism is confirmed. This article
      provides a contemporary review on cryopreservation of parathyroid tissue and its
      current role in thyroid and parathyroid surgery.

PMID- 21197073
TI  - Changes of immunological profiles in patients with chronic myeloid leukemia in
      the course of treatment.
AB  - In the previous paper of ours we compared, prior to start any treatment, a number
      of immunological parameters in 24 chronic myeloid leukemia patients with the same
      number of healthy subjects matched by age and sex. We found significant
      differences in the levels of immunoglobulins, the C4 component of complement, the
      C-reactive protein, interleukin 6, the composition of lymphocyte population and
      the production of some cytokines by stimulated CD3+ cells. Eleven of these
      patients were followed longitudinally. After treatment with hydroxyurea,
      interferon alpha, imatinib mesylate and dasatinib, or various combinations
      thereof, hematological remission was achieved in all patients and complete
      cytogenetic remission in nine of them. There was a nearly general tendency
      towards normalization of the abnormalities observed in the patients at their
      enrollment.

PMID- 21197074
TI  - Efficacy and Safety of a New Formulation of Pancrelipase (Ultrase MT20) in the
      Treatment of Malabsorption in Exocrine Pancreatic Insufficiency in Cystic
      Fibrosis.
AB  - Background. Pancreatic enzyme replacement therapy is the standard of care for
      treatment of malabsorption in patients with cystic fibrosis (CF) and exocrine
      pancreatic insufficiency (PI). Aim. To evaluate efficacy and safety of a new
      formulation of pancrelipase (Ultrase MT20) in patients with CF and PI.
      Coefficients of fat absorption (CFA%) and nitrogen absorption (CNA%) were the
      main efficacy parameters. Safety was evaluated by monitoring laboratory analyses,
      adverse events (AEs), and overall signs and symptoms. Methods. Patients (n = 31)
      were randomized in a crossover design comparing this pancrelipase with placebo
      during 2 inpatient evaluation periods (6-7 days each). Fat and protein/nitrogen
      ingestion and excretion were measured from food diaries and 72-hour stool
      collections. CFA% and CNA% were calculated for each period and compared. Results.
      Twenty-four patients provided analyzable data. This pancrelipase increased mean
      CFA% and CNA% (+34.7% and +25.7%, resp., P < .0001 for both), reduced stool
      frequency, and improved stool consistency compared with placebo. Placebo-treated
      patients reported more AEs, with gastrointestinal symptoms being the most
      frequently reported AE. Conclusions. This pancrelipase is a safe and effective
      treatment for malabsorption associated with exocrine PI in patients with CF.

PMID- 21197075
TI  - Resilience significantly contributes to exceptional longevity.
AB  - Objective. We aim to investigate whether centenarians are significantly more
      resilient than younger elders and whether resilience significantly contributes to
      exceptional longevity. Data. We use a unique dataset from the Chinese
      Longitudinal Healthy Longevity Survey with the largest sample to date of
      centenarians, nonagenarians, octogenarians, and a compatible group of young old
      aged 65-79. Methods and Results. Logistic regressions based on the cross
      sectional sample show that after controlling for various confounders, including
      physical health and cognitive status, centenarians are significantly more
      resilient than any other old-age group. Logistic regression analyses based on the
      longitudinal data show that nonagenarians aged 94-98 with better resilience have
      a 43.1% higher likelihood of becoming a centenarian compared to nonagenarians
      with lower resilience. Conclusions. Resilience significantly contributes to
      longevity at all ages, and it becomes even more profound at very advanced ages.
      These findings indicate that policies and programs to promote resilience would
      have long-term and positive effects on the well-being and longevity for senior
      citizens and their families.

PMID- 21197076
TI  - Recent advances in understanding the microbiology of the female reproductive
      tract and the causes of premature birth.
AB  - Data derived from molecular microbiological investigations of the human vagina
      have led to the discovery of resident bacterial communities that exhibit marked
      differences in terms of species composition. All undergo dynamic changes that are
      likely due to intrinsic host and behavioral factors. Similar types of bacteria
      have been found in both amniotic fluid and the vagina, suggesting a potential
      route of colonization. Given that not all of the species involved in intrauterine
      infections are readily cultivated, it is important that culture-independent
      methods of analysis must be used to understand the etiology of these infections.
      Further research is needed to establish whether an ascending pathway from the
      vagina to the amniotic cavity enables the development of intrauterine infections.

PMID- 21197077
TI  - Clustering of Mycobacterium tuberculosis cases in Acapulco: Spoligotyping and
      risk factors.
AB  - Recurrence and reinfection of tuberculosis have quite different implications for
      prevention. We identified 267 spoligotypes of Mycobacterium tuberculosis from
      consecutive tuberculosis patients in Acapulco, Mexico, to assess the level of
      clustering and risk factors for clustered strains. Point cluster analysis
      examined spatial clustering. Risk analysis relied on the Mantel Haenszel
      procedure to examine bivariate associations, then to develop risk profiles of
      combinations of risk factors. Supplementary analysis of the spoligotyping data
      used SpolTools. Spoligotyping identified 85 types, 50 of them previously
      unreported. The five most common spoligotypes accounted for 55% of tuberculosis
      cases. One cluster of 70 patients (26% of the series) produced a single
      spoligotype from the Manila Family (Clade EAI2). The high proportion (78%) of
      patients infected with cluster strains is compatible with recent transmission of
      TB in Acapulco. Geomatic analysis showed no spatial clustering; clustering was
      associated with a risk profile of uneducated cases who lived in single-room
      dwellings. The Manila emerging strain accounted for one in every four cases,
      confirming that one strain can predominate in a hyperendemic area.

PMID- 21197078
TI  - Evaluation of Effectiveness of Vitamins C and E on Prevention of Renal Scar due
      to Pyelonephritis in Rat.
AB  - Aim was evaluation of the effects of cosupplementation of, vitamins E and C, in
      preventing renal scarring in acute pyelonephritis. Animals and Treatments. Sixty
      rats were used, bacteria was injected through kidney. The rats were arranged
      randomly in 3 groups of 20 rats each. Rats in groups 1 and 2 were given once
      daily intraperitoneal injections of gentamicin for ten consecutive days,
      beginning on the third day after inoculation. In group 2, vitamins E and C
      cotreatment and in group 3, vitamins E and C cotreatment without gentamicin
      injection were started. Three rats in each group were killed 24 hours after the
      inoculation (for infection and inflammation document) and forty-eight hours after
      the antibiotic injection (for efficacy of treatment). After eight weeks, the rest
      of rats were killed, and kidneys evaluated for percent of scaring. Result. There
      was also significant difference of degree of scar formation (1.4 and 3.4% versus
      8.6%, P = .001). The group which received gentamicin only had moderate to severe
      scaring, but the two groups which received vitamin C and vitamin E showed no or
      mild renal scaring. Conclusion. The study showed that administration of
      antioxidants can protect scaring due to pyelonephritis with or without antibiotic
      administration.

PMID- 21197079
TI  - Why and How Meet n-3 PUFA Dietary Recommendations?
AB  - Obesity and the metabolic syndrome are systemic inflammatory diseases reaching
      epidemic proportions. Contemporary changes in human nutrition occurred
      characterized by increased consumption of fat and of vegetable oils rich in n-6
      polyunsaturated fatty acids (PUFAs) together with decrease in n-3 PUFA-rich
      foods, resulting in an n-6/n-3 ratio of 10-20/1 in Western diet for a ratio
      around 1/1 in the diet of our ancestors. The literature provides compelling
      evidence for the health benefit of n-3 PUFA consumption on inflammation and
      metabolic syndrome prevention and treatment. Such evidence led to the
      establishment of comprehensive recommendations. However, we show here that, both
      in collective catering proposed to children and in hospital diet, it is not
      straightforward to meet such recommendations. Willingness of governments to
      institute changes, with accountable decisions on catering, nutritional education,
      and food processing, is required to face our neglected responsibility in
      promoting balanced diet and consumption of foods rich in essential nutrients in
      the general population.

PMID- 21197081
TI  - The ethics of traditional chinese and Western herbal medicine research: views of
      researchers and human ethics committees in australia.
AB  - Despite the growth of traditional Chinese medicine (TCM) and western herbal
      medicine (WHM) research in Australia, little is known about how ethics committees
      (HRECs) assess the ethics of TCM or WHM research. The objectives of this study
      were to examine the experiences of TCM and WHM researchers and HRECs with the
      evaluation of ethics applications. Two cross-sectional surveys were undertaken of
      HRECs and TCM and WHM researchers in Australia. Anonymous self-completion
      questionnaires were administered to 224 HRECs and 117 researchers. A response
      confirming involvement in TCM or WHM research applications was received from 20
      HRECs and 42 researchers. The most frequent ethical issues identified by HRECs
      related to herbal products including information gaps relating to mode of action
      of herbal medicines and safety when combining herbal ingredients. Researchers
      concurred that they were frequently requested to provide additional information
      on multiple aspects including safety relating to the side effects of herbs and
      herb-drug interactions. Overall adherence with the principles of ethical conduct
      was high among TCM and WHM researchers although our study did identify the need
      for additional information regarding assessment of risk and risk management.

PMID- 21197080
TI  - A novel pathway for the biosynthesis of heme in Archaea: genome-based
      bioinformatic predictions and experimental evidence.
AB  - Heme is an essential prosthetic group for many proteins involved in fundamental
      biological processes in all three domains of life. In Eukaryota and Bacteria heme
      is formed via a conserved and well-studied biosynthetic pathway. Surprisingly, in
      Archaea heme biosynthesis proceeds via an alternative route which is poorly
      understood. In order to formulate a working hypothesis for this novel pathway, we
      searched 59 completely sequenced archaeal genomes for the presence of gene
      clusters consisting of established heme biosynthetic genes and colocalized
      conserved candidate genes. Within the majority of archaeal genomes it was
      possible to identify such heme biosynthesis gene clusters. From this analysis we
      have been able to identify several novel heme biosynthesis genes that are
      restricted to archaea. Intriguingly, several of the encoded proteins display
      similarity to enzymes involved in heme d(1) biosynthesis. To initiate an
      experimental verification of our proposals two Methanosarcina barkeri proteins
      predicted to catalyze the initial steps of archaeal heme biosynthesis were
      recombinantly produced, purified, and their predicted enzymatic functions
      verified.

PMID- 21197082
TI  - Ectopic hidradenoma papilliferum.
AB  - Hidradenoma papilliferum is a rare tumor that occurs almost exclusively in
      females on the anogenital area. Rare cases of ectopic (nongenital) hidradenoma
      papilliferum have been described. The lesions usually present as an asymptomatic
      slow-growing, red, firm, mobile, well-delimitated nodule that grows for a long
      time before resection. We describe a case of an 26-year-old man that presented
      with an enlarging nodule on his right eyelid. The histological findings revealed
      a hidradenoma papilliferum. So far, among the very few reports of ectopic
      hidradenoma papilliferum, only a very small number were localized to the eyelid.

PMID- 21197083
TI  - No Weight Catch-Up Growth of SGA Infants Is Associated with Impaired Insulin
      Sensitivity during the Early Postnatal Period.
AB  - Objective. To investigate the relationship between weight catch-up growth and
      insulin sensitivity in small for gestational age (SGA) infants. Methods. Forty
      four singleton SGA subjects met the inclusion criteria and finished-3-month
      followup. Body weight, length, fasting glucose, and fasting insulin (FI) levels
      were measured at 3 days and 3 months. Insulin sensitivity was evaluated by FI and
      homeostasis model assessment (HOMA). Results. According to the change of weight Z
      score, forty-four subjects were divided into two groups: noncatch-up growth
      (NCUG) and catch-up growth (CUG). By 3 months of age, the body weight, body
      length and BMI of NCUG group were significantly lower than those of CUG group.
      The FI and HOMA were significantly higher in NCUG group. The change of weight Z
      score during 3 months was inversely related to the HOMA at 3 months. Conclusion.
      Our data exemplified that no weight catch-up growth during the first 3 months was
      associated with impaired insulin sensitivity in SGA infants.

PMID- 21197084
TI  - Metabolic Syndrome and Its Individual Components among Jordanian Children and
      Adolescents.
AB  - This study aimed to determine the prevalence of metabolic syndrome (MeS) and its
      individual components in Jordanian children and adolescents aged 7-18 years and
      determine the factors that are associated with clustering of metabolic
      abnormalities. MeS was defined using the International Diabetes Federation (IDF)
      definition. The prevalence of MeS was estimated from 512 subjects who had
      complete information on all MeS components. The prevalence of MeS according to
      IDF criteria was 1.4% in subjects aged between 10 and 15.9 years and 3.6% in
      subjects aged between 16 and 18 years. When categorized according to body mass
      index (BMI), the prevalence of the MeS was 15.1% in obese subjects, compared to
      0.3% in subjects with normal BMI, and 3.0% in overweight subjects. In conclusion,
      our results indicate that although the prevalence of MeS is low in Jordanian
      children and adolescents, a large proportion of them had one or two metabolic
      abnormalities.

PMID- 21197085
TI  - Generation and Analysis of Expressed Sequence Tags from Olea europaea L.
AB  - Olive (Olea europaea L.) is an important source of edible oil which was
      originated in Near-East region. In this study, two cDNA libraries were
      constructed from young olive leaves and immature olive fruits for generation of
      ESTs to discover the novel genes and search the function of unknown genes of
      olive. The randomly selected 3840 colonies were sequenced for EST collection from
      both libraries. Readable 2228 sequences for olive leaf and 1506 sequences for
      olive fruit were assembled into 205 and 69 contigs, respectively, whereas 2478
      were singletons. Putative functions of all 2752 differentially expressed unique
      sequences were designated by gene homology based on BLAST and annotated using
      BLAST2GO. While 1339 ESTs show no homology to the database, 2024 ESTs have
      homology (under 80%) with hypothetical proteins, putative proteins, expressed
      proteins, and unknown proteins in NCBI-GenBank. 635 EST's unique genes sequence
      have been identified by over 80% homology to known function in other species
      which were not previously described in Olea family. Only 3.1% of total EST's was
      shown similarity with olive database existing in NCBI. This generated EST's data
      and consensus sequences were submitted to NCBI as valuable source for functional
      genome studies of olive.

PMID- 21197087
TI  - Interactions of overweight, poor oral health, and stress related to chronic
      disease in an aging population.
AB  - The prevalence of excess body mass (XBM), poor oral health (POH), and stress in a
      secluded population of aged (>=60 years) Hmong immigrants was surveyed. The
      findings were related to the prevalence of diabetes in the same population.
      Diabetes was associated separately with POH (OR 2.4; CL 1.3, 4.2) or with XBM (OR
      2.5; CL 1.4, 4.8). The association of diabetes with the combination of XBM and
      POH was striking (OR 5.1; CL 3.4, 7.5); that apparent synergism has not been
      fully appreciated. We describe a mechanism that explains the synergism. The
      concept of "thrifty genotype" is a plausible explanation of XBM in the elderly
      Hmong immigrants and possibly the current older Laotian population. POH is common
      among elderly Laotians as it is in most developing countries. We conclude that
      synergism of XBM and POH significantly elevates the prevalence of diabetes among
      aging populations and probably other age groups as well.

PMID- 21197086
TI  - Melatonin and its agonist ramelteon in Alzheimer's disease: possible therapeutic
      value.
AB  - Alzheimer's disease (AD) is an age-associated neurodegenerative disease
      characterized by the progressive loss of cognitive function, loss of memory and
      insomnia, and abnormal behavioral signs and symptoms. Among the various theories
      that have been put forth to explain the pathophysiology of AD, the oxidative
      stress induced by amyloid beta-protein (Abeta) deposition has received great
      attention. Studies undertaken on postmortem brain samples of AD patients have
      consistently shown extensive lipid, protein, and DNA oxidation. Presence of
      abnormal tau protein, mitochondrial dysfunction, and protein hyperphosphorylation
      all have been demonstrated in neural tissues of AD patients. Moreover, AD
      patients exhibit severe sleep/wake disturbances and insomnia and these are
      associated with more rapid cognitive decline and memory impairment. On this
      basis, the successful management of AD patients requires an ideal drug that
      besides antagonizing Abeta-induced neurotoxicity could also correct the disturbed
      sleep-wake rhythm and improve sleep quality. Melatonin is an effective
      chronobiotic agent and has significant neuroprotective properties preventing
      Abeta-induced neurotoxic effects in a number of animal experimental models. Since
      melatonin levels in AD patients are greatly reduced, melatonin replacement has
      the potential value to be used as a therapeutic agent for treating AD,
      particularly at the early phases of the disease and especially in those in whom
      the relevant melatonin receptors are intact. As sleep deprivation has been shown
      to produce oxidative damage, impaired mitochondrial function, neurodegenerative
      inflammation, and altered proteosomal processing with abnormal activation of
      enzymes, treatment of sleep disturbances may be a priority for arresting the
      progression of AD. In this context the newly introduced melatonin agonist
      ramelteon can be of much therapeutic value because of its highly selective action
      on melatonin MT(1)/MT(2) receptors in promoting sleep.

PMID- 21197088
TI  - Is musculoskeletal ultrasonography an operator-dependent method or a fast and
      reliably teachable diagnostic tool? Interreader agreements of three
      ultrasonographers with different training levels.
AB  - Objectives. To assess interreader agreements and a learning curve between three
      (senior, junior, and beginner) different experienced musculoskeletal
      ultrasonographers. Senior served as the imaging "gold standard". Methods.
      Clinically dominant joints (finger, shoulder, knee, tibiotalar, and
      talonavicular) of 15 rheumatoid arthritis (RA) patients were examined by three
      different experienced ultrasonographers (senior 10 years, junior 10 months, and
      beginner one month). Each patient's ultrasonographic findings were reported
      unaware of the other investigators' results. kappa coefficients, percentage
      agreements, sensitivities, and specificities were calculated. Results. 120 joints
      of 15 RA patients were evaluated. Comparing junior's and beginner's results each
      to the senior's findings, the overall kappa for all examined joints was 0.83
      (93%) for junior and 0.43 (76%) for beginner. Regarding the different joints,
      junior's findings correlate very well with the senior's findings (finger joints:
      kappa = 0.82; shoulder: kappa = 0.9; knee: kappa = 0.74; tibiotalar joint: kappa
      = 0.84; talonavicular joint: kappa = 0.84) while beginner's findings just showed
      fair to moderate agreements (finger joints: kappa = 0.4; shoulder: kappa = 0.42;
      knee: kappa = 0.4; tibiotalar joint: kappa = 0.59; talonavicular joint: kappa =
      0.35). In total, beginner's results clearly improved from kappa = 0.34 (agreement
      of 67%) at baseline to kappa = 0.78 (agreement of 89%) at the end of the
      evaluation period. Conclusions. Ultrasonographic evaluation of a ten-month
      experienced investigator in comparison to a senior ultrasonographer was of
      substantial agreement. Agreements between a beginner and a highly experienced
      ultrasonographer were only fair at the beginning, but during the study including
      ultrasonographical sessions of 15 RA patients, the beginner clearly improved in
      musculoskeletal ultrasonography.

PMID- 21197089
TI  - Profound Vitamin D Deficiency in a Diverse Group of Women during Pregnancy Living
      in a Sun-Rich Environment at Latitude 32 degrees N.
AB  - OBJECTIVE: Determine prevalence of vitamin D deficiency (VDD) in a diverse group
      of women presenting for obstetrical care at two community health centers in South
      Carolina at latitude 32 degrees N. METHODS AND DESIGN: Any pregnant woman
      presenting for care at 2 community health centers was eligible to participate.
      Sociodemographic and clinical history were recorded. A single blood sample was
      taken to measure circulating 25(OH)D as indicator of vitamin D status [25(OH)D <
      20 ng/mL (50 nmol/L deficiency; <32 ng/mL (80 nmol/L) insufficiency]. Total serum
      calcium, phosphorus, creatinine, and intact parathyroid hormone also were
      measured. RESULTS: 559 women, [mean age 25.0 +/- 5.4 (range 14-43) years]
      participated: African American (48%), Hispanic (38%), Caucasian/Other (14%). Mean
      gestational age was 18.5 +/- 8.4 (median 14.6, range 6.4-39.6) weeks' gestation.
      48% were VDD; an additional 37% insufficient. Greatest degree was in the African
      American women (68% deficient; 94% insufficient). In multivariable regression,
      25(OH)D retained a significant negative association with PTH (P < .001).
      CONCLUSIONS: VDD was high in a diverse group of women, greatest in those of
      darker pigmentation. The negative correlation between 25(OH)D and PTH confirms
      their corroborative use as biomarkers of VDD. These findings raise the issue of
      adequacy of current vitamin D recommendations for pregnant women.

PMID- 21197090
TI  - Cytokine production by peripheral blood CD4+ and CD8+ T cells in atopic childhood
      asthma.
AB  - There are conflicting studies on T cell cytokine production in childhood asthma.
      In this study intracellular cytokine expression of IL-2, IL-4, IL-10, IL-13, IFN
      gamma, and TNF-alpha in CD4(+) and CD8(+) T cells in children with atopic asthma
      were measured by flow cytometry. Results. A significant increase in the
      percentage of CD4(+) and CD8(+) T cells producing IL-4 and IL-13 and decrease in
      the percentage of CD4(+) producing IFN-gamma in asthmatic children was found. The
      percentage of CD4(+)/IL-13(+) was significantly higher in severe asthma than in
      children with intermittent disease symptoms. Severity of asthma was associated
      with increased both serum IgE and frequencies of CD4(+)/IL-13(+) T cells, as well
      as duration of disease. Moreover, a decrease in FEV(1), FEV(1)/FVC was observed
      in relation to the severity of asthma. Changes in cytokine profile in CD8(+)
      subpopulation didn't depend on the severity of the disease. Conclusions.
      Increased production of IL-4 and IL-13 in both CD4(+) and CD8(+) T cells
      accompanied by decreased IFN-gamma expression in CD4(+) T cells may be evidence
      that both lymphocyte subpopulations are implicated in the pathogenesis of asthma.
      Relationship of CD4(+)/IL-13(+) T cells with disease activity suggests that this
      lymphocyte subset may have a prominent role in childhood asthma.

PMID- 21197091
TI  - Antiretroviral treatment-associated tuberculosis in a prospective cohort of HIV
      infected patients starting ART.
AB  - Commencement of antiretroviral treatment (ART) in severely immunosuppressed HIV
      infected persons is associated with unmasking of subclinical disease. The subset
      of patients that are diagnosed with tuberculosis (TB) disease while on ART have
      been classified as ART-associated TB. Few studies have reported the incidence of
      ART-associated TB and unmasking TB-IRIS according to the International Network
      for the Study of HIV-Associated IRIS (INSHI) consensus definition. To determine
      the incidence and predictors of ART-associated TB, we screened 219 patients
      commencing ART at the Infectious Diseases Clinic in Kampala, Uganda for TB by
      symptoms, sputum microscopy, and chest X-rays and followed them for one year.
      Fourteen (6.4%) patients were diagnosed with TB during followup. Eight (3.8%)
      patients had ART-associated TB (incidence rate of 4.3 per 100 person years); of
      these, three patients fulfilled INSHI criteria for unmasking TB-associated IRIS
      (incidence rate of 1.6 per 100 person years). A body mass index of less than 18.5
      kg/m(2) BMI (HR 5.85 95% CI 1.24-27.46, P = .025) and a C-reactive protein
      greater than 5 mg/L (HR 8.23 95% CI 1.36-38.33, P = .020) were risk factors for
      ART-associated TB at multivariate analysis. In conclusion, with systematic TB
      screening (including culture and chest X-ray), the incidence of ART-associated TB
      is relatively low in settings with high HIV and TB prevalence.

PMID- 21197092
TI  - Construction and characterization of insect cell-derived influenza VLP: cell
      binding, fusion, and EGFP incorporation.
AB  - We have constructed virus-like particles (VLPs) harboring hemagglutinin (HA),
      neuraminidase (NA), matrix protein 1 (M1) ,and proton channel protein (M2) using
      baculovirus as a vector in the SF9 insect cell. The size of the expressed VLP was
      estimated to be ~100 nm by light scattering experiment and transmission electron
      microscopy. Recognition of HA on the VLP surface by the HA2-specific monoclonal
      antibody IIF4 at acidic pH, as probed by surface plasmon resonance, indicated the
      pH-induced structural rearrangement of HA. Uptake of the particle by A549
      mediated by HA-sialylose receptor interaction was visualized by the fluorescent
      labeled VLP. The HA-promoted cell-virus fusion activity was illustrated by
      fluorescence imaging on the Jurkat cells incubated with rhodamine-loaded VLP
      performed at fusogenic pH. Furthermore, the green fluorescence protein (GFP) was
      fused to NA to produce VLP with a pH-sensitive probe, expanding the use of VLP as
      an antigen carrier and a tool for viral tracking.

PMID- 21197093
TI  - Psorinum therapy in treating stomach, gall bladder, pancreatic, and liver
      cancers: a prospective clinical study.
AB  - We prospectively studied the clinical efficacy of an alternative cancer treatment
      "Psorinum Therapy" in treating stomach, gall bladder, pancreatic and liver
      cancers. Our study was observational, open level and single arm. The
      participants' eligibility criteria included histopathology/cytopathology
      confirmation of malignancy, inoperable tumor, and no prior chemotherapy or
      radiation therapy. The primary outcome measures of the study were (i) to assess
      the radiological tumor response (ii) to find out how many participants survived
      at least 1 year, 2 years, 3 years, 4 years and finally 5 years after the
      beginning of the study considering each type of cancer. Psorinum-6x was
      administered orally to all the participants up to 0.02 ml/Kg body weight as a
      single dose in empty stomach per day for 2 years along with allopathic and
      homeopathic supportive cares. 158 participants (42 of stomach, 40 of gall
      bladder, 44 of pancreatic, 32 of liver) were included in the final analysis of
      the study. Complete tumor response occurred in 28 (17.72%) cases and partial
      tumor response occurred in 56 (35.44%) cases. Double-blind randomized controlled
      clinical trial should be conducted for further scientific exploration of this
      alternative cancer treatment.

PMID- 21197094
TI  - MRI superresolution using self-similarity and image priors.
AB  - In Magnetic Resonance Imaging typical clinical settings, both low- and high
      resolution images of different types are routinarily acquired. In some cases, the
      acquired low-resolution images have to be upsampled to match with other high
      resolution images for posterior analysis or postprocessing such as registration
      or multimodal segmentation. However, classical interpolation techniques are not
      able to recover the high-frequency information lost during the acquisition
      process. In the present paper, a new superresolution method is proposed to
      reconstruct high-resolution images from the low-resolution ones using information
      from coplanar high resolution images acquired of the same subject. Furthermore,
      the reconstruction process is constrained to be physically plausible with the MR
      acquisition model that allows a meaningful interpretation of the results.
      Experiments on synthetic and real data are supplied to show the effectiveness of
      the proposed approach. A comparison with classical state-of-the-art interpolation
      techniques is presented to demonstrate the improved performance of the proposed
      methodology.

PMID- 21197096
TI  - The differential expression of aqueous soluble proteins in breast normal and
      cancerous tissues in relation to stage and grade of patients.
AB  - Breast cancer is a leading cause of female deaths worldwide. In Malaysia, it is
      the most common form of female cancer while Infiltrating ductal carcinoma (IDC)
      is the most common form of breast cancer. A proteomic approach was used to
      identify changes in the protein profile of breast cancerous and normal tissues.
      The patients were divided into different cohorts according to tumour stage and
      grade. We identified twenty-four differentially expressed hydrophilic proteins. A
      few proteins were found significantly related to various stages and grades of
      IDC, amongst which were SEC13-like 1 (isoform b), calreticulin, 14-3-3 protein
      zeta, and 14-3-3 protein eta. In this study, we found that by defining the
      expression of the proteins according to stages and grades of IDC, a significant
      relationship between the expression of the proteins with the stage or grade of
      IDC can be established, which increases the usefulness of these proteins as
      biomarkers for IDC.

PMID- 21197095
TI  - Tuberculosis immunity: opportunities from studies with cattle.
AB  - Mycobacterium tuberculosis and M. bovis share >99% genetic identity and induce
      similar host responses and disease profiles upon infection. There is a rich
      history of codiscovery in the development of control measures applicable to both
      human and bovine tuberculosis (TB) including skin-testing procedures, M. bovis
      BCG vaccination, and interferon-gamma release assays. The calf TB infection model
      offers several opportunities to further our understanding of TB
      immunopathogenesis. Recent observations include correlation of central memory
      immune responses with TB vaccine efficacy, association of SIRPalpha(+) cells in
      ESAT-6:CFP10-elicited multinucleate giant cell formation, early gammadelta T cell
      responses to TB, antimycobacterial activity of memory CD4(+) T cells via
      granulysin production, association of specific antibody with antigen burden, and
      suppression of innate immune gene expression in infected animals. Partnerships
      teaming researchers with veterinary and medical perspectives will continue to
      provide mutual benefit to TB research in man and animals.

PMID- 21197098
TI  - Anhedonia and pessimism in hospitalized depressed adolescents.
AB  - This longitudinal study investigates whether anhedonia and pessimistic
      attributional style represent a clinical state or a trait in hospitalized
      depressed adolescents. 81 consecutive adolescent inpatients were screened with
      the Beck Depression Inventory (BDI) and the clinician-rated Major Depressive
      Disorder (MDD) criteria sheet. 51 patients with BDI score >=10 and/or >=4
      symptoms on MDD criteria sheet were assessed at Time 1 upon admission, with 39
      patients (78%) assessed at discharge (Time 2) with the Pleasure Scale for
      Children and Children's Attributional Style Questionnaire-Revised. Anhedonia and
      pessimism at admission were associated with BDI scores at admission and discharge
      as well as number of depressive symptoms and depression severity. MDD diagnosis
      was associated with anhedonia, but not with pessimism. Pessimism-but not
      anhedonia-improved significantly by discharge. Results suggest that while some
      adolescents exhibit enduring anhedonia, pessimistic attributional style appears
      to be a concomitant feature of an acute depressive state.

PMID- 21197097
TI  - Review: magnetic resonance spectroscopy studies of pediatric major depressive
      disorder.
AB  - Introduction. This paper focuses on the application of Magnetic Resonance
      Spectroscopy (MRS) to the study of Major Depressive Disorder (MDD) in children
      and adolescents. Method. A literature search using the National Institutes of
      Health's PubMed database was conducted to identify indexed peer-reviewed MRS
      studies in pediatric patients with MDD. Results. The literature search yielded 18
      articles reporting original MRS data in pediatric MDD. Neurochemical alterations
      in Choline, Glutamate, and N-Acetyl Aspartate are associated with pediatric MDD,
      suggesting pathophysiologic continuity with adult MDD. Conclusions. The MRS
      literature in pediatric MDD is modest but growing. In studies that are
      methodologically comparable, the results have been consistent. Because it offers
      a noninvasive and repeatable measurement of relevant in vivo brain chemistry, MRS
      has the potential to provide insights into the pathophysiology of MDD as well as
      the mediators and moderators of treatment response.

PMID- 21197100
TI  - Hopelessness and Excessive Drinking among Aboriginal Adolescents: The Mediating
      Roles of Depressive Symptoms and Drinking to Cope.
AB  - Canadian Aboriginal youth show high rates of excessive drinking, hopelessness,
      and depressive symptoms. We propose that Aboriginal adolescents with higher
      levels of hopelessness are more susceptible to depressive symptoms, which in turn
      predispose them to drinking to cope-which ultimately puts them at risk for
      excessive drinking. Adolescent drinkers (n = 551; 52% boys; mean age = 15.9
      years) from 10 Canadian schools completed a survey consisting of the substance
      use risk profile scale (hopelessness), the brief symptom inventory (depressive
      symptoms), the drinking motives questionnaire-revised (drinking to cope), and
      quantity, frequency, and binge measures of excessive drinking. Structural
      equation modeling demonstrated the excellent fit of a model linking hopelessness
      to excessive drinking indirectly via depressive symptoms and drinking to cope.
      Bootstrapping indicated that this indirect effect was significant. Both
      depressive symptoms and drinking to cope should be intervention targets to
      prevent/decrease excessive drinking among Aboriginal youth high in hopelessness.

PMID- 21197099
TI  - Can basic risk research help in the prevention of childhood and adolescent
      depression? Examining a cognitive and emotional regulation approach.
AB  - This paper aims to highlight ways in which basic research findings in the field
      of childhood and adolescent depression can help to inform and refine preventive
      intervention efforts. We selectively review basic research evidence from
      community, clinical, and high-risk populations that identifies cognitive
      mechanisms (thought processes and reactions to negative affect) and emotional
      regulation as key processes involved in the onset and maintenance of depression.
      We focus on cognitive and emotional mechanisms in order to allow comparability
      with the majority of current preventive interventions. A range of basic research
      strategies and studies are then suggested that could be employed to help the
      development and refinement of prevention strategies. These include the need for
      prospective longitudinal studies to identify causal risk and protective factors,
      an integration of research approaches and methods, and a focus on understanding
      potential aetiological heterogeneity between childhood and adolescent depression.

PMID- 21197101
TI  - Depression with and without Comorbid Substance Dependence in a Child Welfare
      Sample of Young Adults.
AB  - The objective of this study was to estimate the prevalence of depression with and
      without substance dependence and examine the effect of risk factors on subsequent
      disorders among a cohort of young adults in the US Child Welfare System (CWS). We
      used longitudinal data for 834 young adults age 18-21 from the National Survey of
      Child and Adolescent Well-being. Depressive symptoms and substance use were
      measured at baseline (age 11-15); diagnoses of depression and substance
      dependence were identified at the last wave of data collection (age 18-21).
      Likelihood of subsequent depression with or without substance dependence was
      three times higher for those with clinically significant depressive symptoms at
      baseline. Frequent use of substances at baseline significantly increased the
      likelihood of subsequent depression with comorbid substance dependence compared
      to depression alone. These results support screening youth in the CWS at younger
      ages for both depressive symptoms and substance use with the hope that these
      disorders can be detected earlier.

PMID- 21197102
TI  - Metalloproteinase inhibitors: status and scope from marine organisms.
AB  - Marine environment has been the source of diverse life forms that produce
      different biologically active compounds. Marine organisms are consistently
      contributing with unparalleled bioactive compounds that have profound
      applications in nutraceuticals, cosmeceuticals, and pharmaceuticals. In this
      process, screening of natural products from marine organisms that could
      potentially inhibit the expression of metalloproteinases has gained a huge
      popularity, which became a hot field of research in life sciences.
      Metalloproteinases, especially, matrix metalloproteinases (MMPs) are a class of
      structurally similar enzymes that contribute to the extracellular matrix
      degradation and play major role in normal and pathological tissue remodeling.
      Imbalance in the expression of MMPs leads to severe pathological condition that
      could initiate cardiac, cartilage, and cancer-related diseases. Three decades of
      endeavor for designing potent matrix metalloproteinase inhibitory substances
      (MMPIs) with many not making upto final clinical trials seek new resources for
      devising MMPIs. Umpteen number of medicinally valuable compounds being reported
      from marine organisms, which encourage current researchers to screen potent MMPIs
      from marine organisms. In this paper, we have made an attempt to report the
      metalloproteinase inhibiting substances from various marine organisms.

PMID- 21197103
TI  - Photodynamic therapy with the silicon phthalocyanine pc 4 induces apoptosis in
      mycosis fungoides and sezary syndrome.
AB  - Our current focus on the effects of Photodynamic Therapy (PDT) using silicon
      phthalocyanine Pc 4 photosensitizer on malignant T lymphocytes arose due to
      preclinical observations that Jurkat cells, common surrogate for human T cell
      lymphoma, were more sensitive to Pc 4-PDT-induced killing than epidermoid
      carcinoma A431 cells. Mycosis fungoides (MF) as well as Sezary syndrome (SS) are
      variants of cutaneous T-cell lymphoma (CTCL) in which malignant T-cells invade
      the epidermis. In this study, we investigated the cytotoxicity of Pc 4-PDT in
      peripheral blood cells obtained from patients with SS and in skin biopsies of
      patients with MF. Our data suggest that Pc 4-PDT preferentially induces apoptosis
      of CD4(+)CD7(-) malignant T-lymphocytes in the blood relative to CD11b(+)
      monocytes and nonmalignant T-cells. In vivo Pc 4-PDT of MF skin also photodamages
      the antiapoptotic protein Bcl-2.

PMID- 21197104
TI  - Gene Expression Profiling for In Silico Microdissection of Hodgkin's Lymphoma
      Microenvironment and Identification of Prognostic Features.
AB  - Gene expression profiling studies based on DNA microarrays have demonstrated
      their ability to define the interaction pathways between neoplastic and
      nonmalignant stromal cells in cancer tissues. During the past ten years, a number
      of approaches including microdissection have tried to resolve the variability in
      DNA microarray measurements stemming from cancer tissue sample heterogeneity.
      Another approach, designated as virtual or in silico microdissection, avoids the
      laborious and time-consuming step of anatomic microdissection. It consists of
      confronting the gene expression profiles of complex tissue samples to those of
      cell lines representative of different cell lineages, different differentiation
      stages, or different signaling pathways. This strategy has been used in recent
      studies aiming to analyze microenvironment alterations using gene expression
      profiling of nonmicrodissected classical Hodgkin lymphoma tissues in order to
      generate new prognostic factors. These recent contributions are detailed and
      discussed in the present paper.

PMID- 21197106
TI  - Inhibition of Epidermal Growth Factor Receptor and PI3K/Akt Signaling Suppresses
      Cell Proliferation and Survival through Regulation of Stat3 Activation in Human
      Cutaneous Squamous Cell Carcinoma.
AB  - Recent studies have emphasized the important role of Stat3 activation in a number
      of human tumors from the viewpoint of its oncogenic and antiapoptotic activity.
      In this study, we examined the role and related signaling molecules of Stat3 in
      the carcinogenesis of human cutaneous squamous cell carcinoma (SCC). In 35 human
      cutaneous SCC samples, 86% showed overexpression of phosphorylated (p)-Stat3, and
      most of those simultaneously overexpressed p-EGFR or p-Akt. Constitutive
      activation of EGFR and Stat3 was observed in three SCC cell lines and four of
      five SCC tissues. AG1478, an inhibitor of the EGFR, downregulated Stat3
      activation in HSC-1 human SCC cells. AG1478 inhibited cell proliferation and
      induced apoptosis of HSC-1 cells but did not inhibit the growth of normal human
      epidermal keratinocytes that did not show Stat3 activation. Furthermore, a PI3K
      inhibitor also suppressed Stat3 activation in HSC-1 cells to some degree.
      Combined treatment with the PI3K inhibitor and AG1478 strongly suppressed Stat3
      activity and dramatically induced apoptosis of HSC-1 cells. These data suggest
      that Stat3 activation through EGFR and/or PI3K/Akt activation plays a critical
      role in the proliferation and survival of human cutaneous SCC.

PMID- 21197105
TI  - Proximal tubule cell hypothesis for cardiorenal syndrome in diabetes.
AB  - Incidence of cardiovascular disease (CVD) is remarkably high among patients with
      chronic kidney disease (CKD), even in the early microalbuminuric stages with
      normal glomerular filtration rates. Proximal tubule cells (PTCs) mediate
      metabolism and urinary excretion of vasculotoxic substances via apical and
      basolateral receptors and transporters. These cells also retrieve
      vasculoprotective substances from circulation or synthesize them for release into
      the circulation. PTCs are also involved in the uptake of sodium and phosphate,
      which are critical for hemodynamic regulation and maintaining the mineral
      balance, respectively. Dysregulation of PTC functions in CKD is likely to be
      associated with the development of CVD and is linked to the progression to end
      stage renal disease. In particular, PTC dysfunction occurs early in diabetic
      nephropathy, a leading cause of CKD. It is therefore important to elucidate the
      mechanisms of PTC dysfunction to develop therapeutic strategies for treating
      cardiorenal syndrome in diabetes.

PMID- 21197108
TI  - Adverse life events and depressive symptoms in african american youth: the role
      of control-related beliefs.
AB  - The association between experiences of adverse life events and adolescent
      depressive symptoms has been well documented. However, this association is not
      consistently observed in urban and low income African American youth. In
      addition, mechanisms linking life event stress and African American adolescents'
      depressive symptoms have received little attention. This study examined past year
      violent and nonviolent life events assessed in 6th grade as predictors of 7th
      grade depressive symptoms among a community epidemiologically defined sample of
      447 (47% girls) urban African American adolescents. Depressive symptoms were
      assessed twice, at a 1-year interval, and initial depressive symptoms were
      controlled in the analyses. Control-related beliefs were examined as mediators of
      the association between life events and depressive symptoms, and gender was
      examined as a moderator of the association between control-related beliefs and
      depressive symptoms. Associations among study variables were examined in a series
      of models, from general to more specific. A model in which nonviolent and violent
      life events were examined separately and control and contingency beliefs examined
      as one latent variable was the most informative about the etiology of depressive
      symptoms in a sample of urban, African American youth. Implications of the
      findings for preventive interventions and future research are discussed.

PMID- 21197107
TI  - Mechanisms of oxidative damage in multiple sclerosis and a cell therapy approach
      to treatment.
AB  - Although significant advances have recently been made in the understanding and
      treatment of multiple sclerosis, reduction of long-term disability remains a key
      goal. Evidence suggests that inflammation and oxidative stress within the central
      nervous system are major causes of ongoing tissue damage in the disease. Invading
      inflammatory cells, as well as resident central nervous system cells, release a
      number of reactive oxygen and nitrogen species which cause demyelination and
      axonal destruction, the pathological hallmarks of multiple sclerosis. Reduction
      in oxidative damage is an important therapeutic strategy to slow or halt disease
      processes. Many drugs in clinical practice or currently in trial target this
      mechanism. Cell-based therapies offer an alternative source of antioxidant
      capability. Classically thought of as being important for myelin or cell
      replacement in multiple sclerosis, stem cells may, however, have a more important
      role as providers of supporting factors or direct attenuators of the disease. In
      this paper we focus on the antioxidant properties of mesenchymal stem cells and
      discuss their potential importance as a cell-based therapy for multiple
      sclerosis.

PMID- 21197109
TI  - Therapeutic options for the management of the cardiorenal syndrome.
AB  - Patients with heart failure often present with impaired renal function, which is
      a predictor of poor outcome. The cardiorenal syndrome is the worsening of renal
      function, which is accelerated by worsening of heart failure or acute
      decompensated heart failure. Although it is a frequent clinical entity due to the
      improved survival of heart failure patients, still its pathophysiology is not
      well understood, and thus its therapeutic approach remains controversial and
      sometimes ineffective. Established therapeutic strategies, such as diuretics and
      inotropes, are often associated with resistance and limited clinical success.
      That leads to an increasing concern about novel options, such as the use of
      vasopressin antagonists, adenosine A1 receptor antagonists, and renal-protective
      dopamine. Initial clinical trials have shown quite encouraging results in some
      heart failure subpopulations but have failed to demonstrate a clear beneficial
      role of these agents. On the other hand, ultrafiltration appears to be a more
      promising therapeutic procedure that will improve volume regulation, while
      preserving renal and cardiac function. Further clinical studies are required in
      order to determine their net effect on renal function and potential
      cardiovascular outcomes. Until then, management of the cardiorenal syndrome
      remains quite empirical.

PMID- 21197110
TI  - Aging, resistance training, and diabetes prevention.
AB  - With the aging of the baby-boom generation and increases in life expectancy, the
      American population is growing older. Aging is associated with adverse changes in
      glucose tolerance and increased risk of diabetes; the increasing prevalence of
      diabetes among older adults suggests a clear need for effective diabetes
      prevention approaches for this population. The purpose of paper is to review what
      is known about changes in glucose tolerance with advancing age and the potential
      utility of resistance training (RT) as an intervention to prevent diabetes among
      middle-aged and older adults. Age-related factors contributing to glucose
      intolerance, which may be improved with RT, include improvements in insulin
      signaling defects, reductions in tumor necrosis factor-alpha, increases in
      adiponectin and insulin-like growth factor-1 concentrations, and reductions in
      total and abdominal visceral fat. Current RT recommendations and future areas for
      investigation are presented.

PMID- 21197111
TI  - ADAM and ADAMTS gene expression in native and wound healing human lens epithelial
      cells.
AB  - PURPOSE: The ADAMs (a disintegrin and metalloproteinase) and the ADAMTSs (a
      disintegrin and metalloproteinase with thrombospondin-like motifs) are
      extracellular proteases that mediate cellular interactions and cell signaling via
      the modulation of adhesion and the cleavage of cell surface protein ectodomains
      and extracellular matrix molecules. Gene expression profiling was undertaken to
      better understand the role of the ADAM and ADAMTS families in the clear native
      human lenses and following surgical injury with particular relevance to posterior
      capsule opacification. METHODS: To carry out profile analysis, the lens (t=0d)
      was dissected into three regions; anterior epithelia, equatorial region, and
      fiber cells. Capsular bag culture was undertaken as a means of assessing short
      term changes (t=6d) and post-cataractous lens capsular bags (ex vivo) were used
      to predict long-term changes in ADAM/ADAMTS gene expression. RNA was isolated and
      quantitative real-time (TaqMan) reverse transcription-PCR (RT-PCR) performed.
      Data were analyzed in terms of cycle threshold number (C(T)) and also normalized
      relative to endogenous 18S rRNA. RESULTS: High expression of ADAM-9, -10, -15,
      and -17 was detected in all native lens regions. ADAM-15 expression was a
      characteristic of the native lens epithelia more than the fibers. Post-surgical
      injury, lens capsular bags showed a positive shift in ADAM/ADAMTS expression that
      was significant for ADAM-9, -15, and ADAMTS-3. Ex vivo capsular bags, with a long
      term post surgical injury period, maintained high expression of ADAM-9 and -10
      genes. CONCLUSIONS: The native human lens expresses ADAM and ADAMTS genes that
      are differentially regulated following surgical injury. Roles in maintaining
      cellular adhesion may be of particular importance to native lens tissue integrity
      and may be lost in the lens wound healing response following cataract surgery.

PMID- 21197112
TI  - Examining the influence of ultraviolet C irradiation on recombinant human gammaD
      crystallin.
AB  - PURPOSE: Human gammaD crystallin is a principal protein component of the human
      eye lens and associated with the development of juvenile and mature-onset
      cataracts. Exposure to ultraviolet (UV) light is thought to perturb protein
      structure and eventually lead to aggregation. This work is aimed at exploring the
      effects of UV-C irradiation on recombinant human gammaD-crystallin (HGDC).
      METHODS: Recombinant HGDC proteins were expressed in E. coli strain BL21(DE3)
      harboring plasmid pEHisHGDC and purified using chromatographic methods. The
      proteins were then exposed to UV-C light (lambda(max)=254 nm, 15 W) at the
      intensity of 420, 800, or 1850 MUW/cm(2). The UV-C-unexposed, supernatant
      fraction of UV-C-exposed, and re-dissolved precipitated fraction of UV-C exposed
      preparations were characterized by SDS-PAGE, turbidity measurement, CD
      spectroscopy, tryptophan fluorescence spectroscopy, acrylamide fluorescence
      quenching analysis, and sulfhydryl group measurements. RESULTS: The turbidity of
      the HGDC sample solution was found to be positively correlated with HGDC
      concentration, UV-C irradiation intensity, and UV-C irradiation duration. When
      exposed to UV-C, HGDC sample solutions became visibly turbid and a noticeable
      amount of larger protein particle, perceptible to the naked eye, was observed
      upon prolonged irradiation. The precipitated fraction of irradiated HGDC sample
      was found to be re-dissolved by guanidine hydrochloride. Electrophoresis,
      acrylamide fluorescence quenching, and spectroscopic analyses revealed
      differences in structures among the non-irradiated HGDC, the supernatant fraction
      of irradiated HGDC, and the re-dissolved precipitated fraction of irradiated
      HGDC. Through the use of L-cysteine, the measurements of sulfhydryl contents, and
      the reducing as well as non-reducing SDS-PAGE, our data further suggested that
      disulfide bond formation and/or cleavage probably play an important role in
      aggregation and/or precipitation of HGDC elicited by UV-C irradiation.
      CONCLUSIONS: Our findings highlight the close connections among disulfide bond
      cleavage and/or formation, intermolecular interactions, and the resultant
      formation of aggregates of HGDC induced by UV-C irradiation. The results from
      this research may not only contribute to the understanding of the environmental
      factors causing protein aggregation but also have implications for deciphering
      the molecular mechanism of cataractogenesis.

PMID- 21197113
TI  - Assessment of canine BEST1 variations identifies new mutations and establishes an
      independent bestrophinopathy model (cmr3).
AB  - PURPOSE: Mutations in bestrophin 1 (BEST1) are associated with a group of retinal
      disorders known as bestrophinopathies in man and canine multifocal retinopathies
      (cmr) in the dog. To date, the dog is the only large animal model suitable for
      the complex characterization and in-depth studies of Best-related disorders. In
      the first report of cmr, the disease was described in a group of mastiff-related
      breeds (cmr1) and the Coton de Tulear (cmr2). Additional breeds, e.g., the
      Lapponian herder (LH) and others, subsequently were recognized with similar
      phenotypes, but linked loci are unknown. Analysis of the BEST1 gene aimed to
      identify mutations in these additional populations and extend our understanding
      of genotype-phenotype associations. METHODS: Animals were subjected to routine
      eye exams, phenotypically characterized, and samples were collected for molecular
      studies. Known BEST1 mutations were assessed, and the canine BEST1 coding exons
      were amplified and sequenced in selected individuals that exhibited a cmr
      compatible phenotype but that did not carry known mutations. Resulting sequence
      changes were genotyped in several different breeds and evaluated in the context
      of the phenotype. RESULTS: Seven novel coding variants were identified in exon 10
      of cBEST1. Two linked mutations were associated with cmr exclusive to the LH
      breed (cmr3). Two individuals of Jamthund and Norfolk terrier breeds were
      heterozygous for two conservative changes, but these were unlikely to have
      disease-causing potential. Another three substitutions were found in the Bernese
      mountain dog that were predicted to have a deleterious effect on protein
      function. Previously reported mutations were excluded from segregation in these
      populations, but cmr1 was confirmed in another mastiff-related breed, the Italian
      cane corso. CONCLUSIONS: A third independent canine model for human
      bestrophinopathies has been established in the LH breed. While exhibiting a
      phenotype comparable to cmr1 and cmr2, the novel cmr3 mutation is predicted to be
      based on a distinctly different molecular mechanism. So far cmr2 and cmr3 are
      exclusive to a single dog breed each. In contrast, cmr1 is found in multiple
      related breeds. Additional sequence alterations identified in exon 10 of cBEST1
      in other breeds exhibit potential disease-causing features. The inherent genetic
      and phenotypic variation observed with retinal disorders in canines is
      complicated further by cmr3 being one of four distinct genetic retinal traits
      found to segregate in LH. Thus, a combination of phenotypic, molecular, and
      population analysis is required to establish a strong phenotype-genotype
      association. These results indicate that cmr has a larger impact on the general
      dog population than was initially suspected. The complexity of these models
      further confirms the similarity to human bestrophinopathies. Moreover, analyses
      of multiple canine models will provide additional insight into the molecular
      basis underlying diseases caused by mutations in BEST1.

PMID- 21197114
TI  - Structural and aggregation behavior of the human gammaD-crystallin mutant E107A,
      associated with congenital nuclear cataract.
AB  - PURPOSE: To analyze the conformational features and aggregation properties of the
      mutant protein E107A human gammaD-crystallin (HGDC), associated with congenital
      nuclear cataract. METHODS: cDNAs of wild type and E107A mutant were cloned and
      expressed in BL21 (DE3) pLysS cells and the proteins isolated and purified. The
      conformational properties and structural stability of the two proteins were
      compared using circular dichroism and fluorescence spectroscopic analysis. His
      tagged cDNAs of the two proteins were transfected into HLE-3B human lens
      epithelial cells, and into HeLa cells and their in situ aggregation properties
      compared using immunofluorescence. RESULTS: The mutant protein was found to be
      remarkably similar in its secondary and tertiary structural features to the wild
      type. Its structural stability, analyzed by guanidinium chloride-induced
      denaturation, was also found to be similar. Its solubility, however, was over
      hundred-fold less than that of the wild type, and it had the tendency to
      precipitate and form light scattering particles. That it had the tendency to self
      aggregate was noticed by using bis-ANS and Nile Red as extrinsic fluorescent
      probes. Such aggregation was also seen in situ when transfected and expressed in
      HLE-3B and in HeLa cell lines. CONCLUSIONS: E107A HGDC is yet another example of
      how a point mutation in the protein does not affect its conformation and
      stability but leads to substantial reduction in solubility and generation of
      light scattering aggregate particles in vitro and in situ when introduced into
      cell lines.

PMID- 21197115
TI  - Analysis of LOXL1 polymorphisms in a Saudi Arabian population with
      pseudoexfoliation glaucoma.
AB  - PURPOSE: To investigate whether single nucleotide polymorphisms (SNPs) in the
      lysyl oxidase-like 1 (LOXL1) gene are associated with pseudoexfoliation glaucoma
      (PEG) in the Saudi Arabian population. METHODS: The coding regions of LOXL1 were
      fully sequenced in 93 clinically diagnosed PEG patients and 101 healthy controls.
      Both groups were Saudi Arabs. Previously reported and newly identified SNPs were
      evaluated for possible association with PEG and their pathological consequences
      on the gene were assessed. RESULTS: The "G" allele frequencies of both rs1048661
      and rs3825942 SNPs differed between PEG patients and control subjects from Saudi
      Arabia (p=0.0056 and p=0.000005, respectively). This significance remained after
      applying the Bonferroni correction. Two non-synonymous novel SNPs in LOXL1 were
      detected in the PEG patients and not in the controls. One of these SNPs was in
      exon 4 (g.25722 C>G; codon change D484E) of LOXL1 and was predicted to be non
      pathological; the other was in exon 6 of LOXL1 (g.28084 T>G; codon change Y559D)
      and was predicted to be probably damaging. All alleles of SNPs (rs28706550,
      rs35203737, rs41429348, rs12906373, rs41435250, and rs13329473) were monoallelic
      in this population. No allele frequency difference for rs8818 and rs3522 SNP
      between patients and controls (p values were 0.126 and 0.994 respectively).
      CONCLUSIONS: Similar to almost all non-African populations tested thus far, the
      "G" allele of both rs1048661 and rs3825942 SNPs were associated with the risk of
      PEG in the Saudi Arab population.

PMID- 21197117
TI  - Additive hazards regression with censoring indicators missing at random.
AB  - In this article, the authors consider a semiparametric additive hazards
      regression model for right-censored data that allows some censoring indicators to
      be missing at random. They develop a class of estimating equations and use an
      inverse probability weighted approach to estimate the regression parameters.
      Nonparametric smoothing techniques are employed to estimate the probability of
      non-missingness and the conditional probability of an uncensored observation. The
      asymptotic properties of the resulting estimators are derived. Simulation studies
      show that the proposed estimators perform well. They motivate and illustrate
      their methods with data from a brain cancer clinical trial.

PMID- 21197116
TI  - Genome-wide association analyses of genetic, phenotypic, and environmental risks
      in the age-related eye disease study.
AB  - PURPOSE: To present genome-wide association analyses of genotypic and
      environmental risks on age-related macular degeneration (AMD) using 593 subjects
      from the age-related eye disease study (AREDS), after adjusting for population
      stratification and including questionable controls. METHODS: Single nucleotide
      polymorphism (SNP) associations with AMD for the non-Hispanic white population
      were investigated using a log-additive model after adjusting for population
      stratification. Replication of possible SNP-disease association was performed by
      genotyping an independent group of 444 AMD case and 300 control subjects.
      Logistic regression models were used to assess interaction effects between
      smoking and SNPs associated with AMD. Independent genetic risk effects among the
      disease-associated SNPs were also investigated using multiple logistic regression
      models. RESULTS: Population stratification was observed among the individuals
      having a self-reported race of non-Hispanic white. Risk allele frequencies at
      established AMD loci demonstrated that questionable control subjects were similar
      to control subjects in the AREDS, suggesting that they could be used as true
      controls in the analyses. Genetic loci (complement factor H [CFH], complement
      factor B [CFB], the age-related maculopathy susceptibility 2 locus containing the
      hypothetical gene [LOC387715]/the high-temperature requirement A-1 [HTRA1], and
      complement component 3 [C3]) that were already known to be associated with AMD
      were identified. An additional 26 novel SNPs potentially associated with AMD were
      identified, but none were definitely replicated in a second independent group of
      subjects. Smoking did not interact with known AMD loci, but was associated with
      late AMD. Statistically independent genetic signals were observed within the
      Pleckstrin homology domain-containing family A member 1 (PLEKHA1) region near
      LOC387715/HTRA1 and within a haplotype spanning exon 19 of the C3 gene.
      CONCLUSIONS: Population stratification among Caucasian subjects from the
      multicentered AREDS was observed, suggesting that it should be adjusted for in
      future studies. The AREDS questionable control subjects can be used as control
      subjects in the AREDS genome-wide association study (GWAS). Smoking was an
      independent risk factor for advanced AMD in the AREDS subjects. There continues
      to be evidence that the 10q26 (age-related maculopathy susceptibility 2 gene
      [ARMS2]) locus spanning PLEKHA1-LOC387715-HTRA1 and the C3 gene may contain
      multiple independent genetic risks contributing to AMD.

PMID- 21197118
TI  - Synthesis of Novel Functionalized 4-Aza-2,3-Didehydropodophyllotoxin Derivatives
      with Potential Antitumor Activity.
AB  - Novel arylamino alcohols were synthesized and these alcohols were used to prepare
      12 novel N-(2-hydroxy-ethyl)-2,3-didehydroazapodophyllotoxins, in one step, by
      simple reflux in ethanol. Isolated yields in the range of 50-70% were obtained.

PMID- 21197119
TI  - Public Library Participation in a MedlinePlus Go Local Project: Perceptions of
      Georgia Librarians and Staff.
AB  - In an effort to promote public library involvement in Georgia Health - Go Local,
      a National Library of Medicine initiative to link consumers to health resources
      in their local areas, staff at a large public library system in south Georgia
      were trained to enter local records into the Go Local database. Results of two
      follow-up focus groups indicated that participants were enthusiastic about
      demonstrating Go Local and MedlinePlus to library users but were not comfortable
      creating or maintaining Go Local records due to concerns about the relevance of
      the project, unease with medical terminology, varied levels of computer
      expertise, and worries about possible liability.

PMID- 21197120
TI  - Health conditions associated with aging and end of life of adults with Down
      syndrome.
AB  - Expectations for the life course of individuals with Down syndrome (DS) have
      changed, with life expectancy estimates increasing from 12 in 1949 to nearly 60
      years of age today (Bittles & Glasson, 2004; Penrose, 1949). Along with this
      longer life expectancy comes a larger population of adults with DS who display
      premature age-related changes in their health. There is thus a need to provide
      specialized health care to this aging population of adults with DS who are at
      high risk for some conditions and at lower risk for others. This review focuses
      on the rates and contributing factors to medical conditions that are common in
      adults with DS or that show changes with age. The review of medical conditions
      includes the increased risk for skin and hair changes, early onset menopause,
      visual and hearing impairments, adult onset seizure disorder, thyroid
      dysfunction, diabetes, obesity, sleep apnea and musculoskeletal problems. The
      different pattern of conditions associated with the mortality of adults with DS
      is also reviewed.

PMID- 21197122
TI  - Eighteen Month Outcomes for Clients Receiving Combined Outpatient Treatment and
      Sober Living Houses.
AB  - One of the most frequent and frustrating challenges facing clients in outpatient
      treatment is finding a living environment that is free of alcohol and drugs and
      supportive of recovery. Sober Living Houses (SLHs) have been suggested as one
      potential solution (Polcin, 2009). Among other advantages, SLHs are financially
      self-sustaining and residents can remain there as long as they wish, provided
      they comply with house rules and expectations. This study examined 18-month
      outcomes for 55 individuals receiving outpatient treatment combined with
      residence in a SLH. Repeated measures analyses comparing 6-month time periods
      showed significant improvement on measures of alcohol and drug use, arrests, and
      days worked. The Addiction Severity Index (ASI) showed significant improvement on
      legal and employment scales. On ASI alcohol and drug scales, individuals entered
      SLHs with very low severity that was maintained at 18 months. Involvement in 12
      step groups was associated with reductions in alcohol and drug use.

PMID- 21197121
TI  - Pharmacologic preconditioning: translating the promise.
AB  - A transient, ischemia-resistant phenotype known as "ischemic tolerance" can be
      established in brain in a rapid or delayed fashion by a preceding noninjurious
      "preconditioning" stimulus. Initial preclinical studies of this phenomenon relied
      primarily on brief periods of ischemia or hypoxia as preconditioning stimuli, but
      it was later realized that many other stressors, including pharmacologic ones,
      are also effective. This review highlights the surprisingly wide variety of drugs
      now known to promote ischemic tolerance, documented and to some extent
      mechanistically characterized in preclinical animal models of stroke. Although
      considerably more experimentation is needed to thoroughly validate the ability of
      any currently identified preconditioning agent to protect ischemic brain, the
      fact that some of these drugs are already clinically approved for other
      indications implies that the growing enthusiasm for translational success in the
      field of pharmacologic preconditioning may be well justified. 

PMID- 21197123
TI  - The self-concept and conjugal loss: evidence for structural change.
AB  - The self-concept is often considered to be a personal resource that individuals
      may use to cope with life stressors, but little is known about how this entity
      might itself change in response to profound stress. The present study examines
      structural change in self-concept following conjugal loss in later life. Analyses
      were conducted on data collected from 57 widows every 4 months over the first 2
      years post-loss. The first objective was to explore the adequacy of an
      operational definition of the self-concept as a latent construct lying at the
      confluence of self-esteem, perceived environmental mastery, and optimism. Because
      confirmatory factor analysis (CFA) supported this theoretically based
      conceptualization, the second objective of the study was to model stability and
      change in the structure of the self-concept over the 2-year study period. Results
      suggested that there is both stability and change in the self-system during the
      adjustment to major life stress.

PMID- 21197124
TI  - Home birth matters-for all women.
AB  - Although it remains rare in the United States, planned home birth has drawn
      increasing attention and criticism in the mainstream media and has come under
      attack from organized medicine. Yet, recent peer-reviewed studies contribute to
      the evidence base supporting home birth as a safe option for low-risk women
      attended by skilled midwives. The author of this editorial argues that home birth
      is an important cultural touchstone in the landscape of American maternity care.

PMID- 21197125
TI  - The most amazing 24 hours.
AB  - In this column, a mother shares the story of her son's birth with her prenatal
      yoga instructor. The mother was able to work with her labor, was well supported
      by her husband and doula, and negotiated successfully with the hospital staff to
      have a safe, healthy birth. She describes how difficult labor is and the ways in
      which comfort and support strategies help women manage contractions.

PMID- 21197126
TI  - Prenatal parental education from the perspective of fathers with experience as
      primary caregiver immediately following birth: a phenomenographic study.
AB  - The aim of this phenomenographic study was to capture fathers' conceptions of
      parental education topics, illuminated by their experiences as primary caregiver
      of their child immediately following birth. Fifteen fathers were interviewed
      between 8 days and 6 weeks after the birth of their child. Three categories, five
      subcategories, and 12 qualitatively different conceptions emerged from the
      study's findings. The first category showed that parental education emphasizes
      the importance of normal birth. The second category illustrated that parental
      education defuses the issue of complicated births. The third category
      demonstrated that parental education preserves traditional gender roles. The
      study's results may facilitate efforts to integrate fathers into parental
      education toward the aim of achieving parity between mother and father in their
      role as parents.

PMID- 21197127
TI  - Parent Involvement in End-of-Life Care and Decision Making in the Newborn
      Intensive Care Unit: An Integrative Review.
AB  - Survival rates for very preterm and critically ill infants are increasing,
      raising complex ethical issues for health-care providers and parents who face the
      challenge of making end-of-life decisions for newborns. The purpose of this
      integrative literature review was to evaluate parental involvement in end-of-life
      care and decision making for their infant in the newborn intensive care unit.
      Findings revealed that establishing good relationships and clear communication
      between health-care providers and parents builds trust and eases stress placed on
      parents making decisions about the care of their infant. Palliative care programs
      provide support for parents and facilitate their decision making. Parents can be
      educated about how to communicate with health-care providers. Educating nurses on
      how to provide end-of-life care may also help improve support for parents during
      this difficult time. Additional research is recommended to examine parents' needs
      during and after end-of-life care decisions for their newborn.

PMID- 21197128
TI  - Factors associated with labor support behaviors of nurses.
AB  - Labor support is known to support progress of normal labor. Nurses are encouraged
      to provide labor support yet may encounter barriers to the practice of labor
      support. The purpose of this secondary data analysis was to examine individual
      and institutional factors associated with labor support behaviors. Age and
      experience were individual factors related to labor support. Older and more
      experienced nurses reported providing more labor support. Institutional factors
      associated with labor support were lower rates of epidural analgesia use and
      cesarean surgery. These findings indicate birthing families should understand
      that the birth environment may influence the care that nurses give during labor.
      Choosing an environment that supports normal birth may be the best place for
      receiving labor supportive nursing care.

PMID- 21197129
TI  - Grant writing for childbirth educators: lessons learned from the resource center
      for young parents-to-be.
AB  - Obtaining funding to support community-based childbirth education programs can be
      a challenge for childbirth educators who may have little grant-writing
      experience. This article was written by two nurse educators/nurse-midwives who
      have been involved for over 10 years with a grant-funded parenting and childbirth
      education program for pregnant teens. It reviews the background of the Resource
      Center for Young Parents-To-Be, suggests grant-funding sources, and explains the
      building of partnerships in the community. The basic steps involved in the grant
      writing process are presented as well as the importance of follow-up evaluations
      and reports. Grant-writing skills and the ability to forge partnerships with
      other community organizations can be important tools for childbirth educators and
      health-care professionals.

PMID- 21197130
TI  - Likelihood estimation for a longitudinal negative binomial regression model with
      missing outcomes.
AB  - Joint damage in psoriatic arthritis can be measured by clinical and radiological
      methods, the former being done more frequently during longitudinal follow-up of
      patients. Motivated by the need to compare findings based on the different
      methods with different observation patterns, we consider longitudinal data where
      the outcome variable is a cumulative total of counts that can be unobserved when
      other, informative, explanatory variables are recorded. We demonstrate how to
      calculate the likelihood for such data when it is assumed that the increment in
      the cumulative total follows a discrete distribution with a location parameter
      that depends on a linear function of explanatory variables. An approach to the
      incorporation of informative observation is suggested. We present analyses based
      on an observational database from a psoriatic arthritis clinic. Although the use
      of the new statistical methodology has relatively little effect in this example,
      simulation studies indicate that the method can provide substantial improvements
      in bias and coverage in some situations where there is an important time varying
      explanatory variable.

PMID- 21197131
TI  - The effect of area of residence over the life course on subsequent mortality.
AB  - Life course epidemiology concentrates on the contribution that social or physical
      exposures have across the life course on adult health. It is known that the area
      of residence can affect health, but little is known about the effect of the area
      of residence across the life course. We examine the contribution that area of
      residence in 1960, 1970, 1980 and 1990 made on subsequent mortality for 49736
      male inhabitants of Oslo in 1990. We compare the performance of multiple
      membership and cross-classified multilevel models on these data with a correlated
      cross-classified model that was developed for this.

PMID- 21197132
TI  - A candidate-set-free algorithm for generating D-optimal split-plot designs.
AB  - We introduce a new method for generating optimal split-plot designs. These
      designs are optimal in the sense that they are efficient for estimating the fixed
      effects of the statistical model that is appropriate given the split-plot design
      structure. One advantage of the method is that it does not require the prior
      specification of a candidate set. This makes the production of split-plot designs
      computationally feasible in situations where the candidate set is too large to be
      tractable. The method allows for flexible choice of the sample size and supports
      inclusion of both continuous and categorical factors. The model can be any linear
      regression model and may include arbitrary polynomial terms in the continuous
      factors and interaction terms of any order. We demonstrate the usefulness of this
      flexibility with a 100-run polypropylene experiment involving 11 factors where we
      found a design that is substantially more efficient than designs that are
      produced by using other approaches.

PMID- 21197133
TI  - Word Mapping and Executive Functioning in Young Monolingual and Bilingual
      Children.
AB  - The effect of bilingualism on the cognitive skills of young children was
      investigated by comparing performance of 162 children who belonged to one of two
      age groups (approximately 3- and 41/2-year-olds) and one of three language groups
      on a series of tasks examining executive control and word mapping. The children
      were monolingual English speakers, monolingual French speakers, or bilinguals who
      spoke English and one of a large number of other languages. Monolinguals obtained
      higher scores than bilinguals on a receptive vocabulary test and were more likely
      to demonstrate the mutual exclusivity constraint, especially at the younger ages.
      However, bilinguals obtained higher scores than both groups of monolinguals on
      three tests of executive functioning: Luria's tapping task measuring response
      inhibition, the Opposite Worlds task requiring children to assign incongruent
      labels to a sequence of animal pictures, and reverse categorization in which
      children needed to reclassify a set of objects into incongruent categories after
      an initial classification. There were no differences between the groups in the
      ANT flanker task requiring executive control to ignore a misleading cue. This
      evidence for a bilingual advantage in aspects of executive functioning at an
      earlier age than previously reported is discussed in terms of the possibility
      that bilingual language production may not be the only source of these
      developmental effects.

PMID- 21197134
TI  - Thermodynamically Constrained Averaging Theory Approach for Modeling Flow and
      Transport Phenomena in Porous Medium Systems: 8. Interface and Common Curve
      Dynamics.
AB  - This work is the eighth in a series that develops the fundamental aspects of the
      thermodynamically constrained averaging theory (TCAT) that allows for a
      systematic increase in the scale at which multiphase transport phenomena is
      modeled in porous medium systems. In these systems, the explicit locations of
      interfaces between phases and common curves, where three or more interfaces meet,
      are not considered at scales above the microscale. Rather, the densities of these
      quantities arise as areas per volume or length per volume. Modeling of the
      dynamics of these measures is an important challenge for robust models of flow
      and transport phenomena in porous medium systems, as the extent of these regions
      can have important implications for mass, momentum, and energy transport between
      and among phases, and formulation of a capillary pressure relation with minimal
      hysteresis. These densities do not exist at the microscale, where the interfaces
      and common curves correspond to particular locations. Therefore, it is necessary
      for a well-developed macroscale theory to provide evolution equations that
      describe the dynamics of interface and common curve densities. Here we point out
      the challenges and pitfalls in producing such evolution equations, develop a set
      of such equations based on averaging theorems, and identify the terms that
      require particular attention in experimental and computational efforts to
      parameterize the equations. We use the evolution equations developed to specify a
      closed two-fluid-phase flow model.

PMID- 21197135
TI  - Design of an FPGA-Based Algorithm for Real-Time Solutions of Statistics-Based
      Positioning.
AB  - We report on the implementation of an algorithm and hardware platform to allow
      real-time processing of the statistics-based positioning (SBP) method for
      continuous miniature crystal element (cMiCE) detectors. The SBP method allows an
      intrinsic spatial resolution of ~1.6 mm FWHM to be achieved using our cMiCE
      design. Previous SBP solutions have required a postprocessing procedure due to
      the computation and memory intensive nature of SBP. This new implementation takes
      advantage of a combination of algebraic simplifications, conversion to fixed
      point math, and a hierarchal search technique to greatly accelerate the
      algorithm. For the presented seven stage, 127 * 127 bin LUT implementation, these
      algorithm improvements result in a reduction from >7 * 10(6) floating-point
      operations per event for an exhaustive search to < 5 * 10(3) integer operations
      per event. Simulations show nearly identical FWHM positioning resolution for this
      accelerated SBP solution, and positioning differences of <0.1 mm from the
      exhaustive search solution. A pipelined field programmable gate array (FPGA)
      implementation of this optimized algorithm is able to process events in excess of
      250 K events per second, which is greater than the maximum expected coincidence
      rate for an individual detector. In contrast with all detectors being processed
      at a centralized host, as in the current system, a separate FPGA is available at
      each detector, thus dividing the computational load. These methods allow SBP
      results to be calculated in real-time and to be presented to the image generation
      components in real-time. A hardware implementation has been developed using a
      commercially available prototype board.

PMID- 21197136
TI  - Music and Autonomic Nervous System (Dys)function.
AB  - Despite a wealth of evidence for the involvement of the autonomic nervous system
      (ANS) in health and disease and the ability of music to affect ANS activity, few
      studies have systematically explored the therapeutic effects of music on ANS
      dysfunction. Furthermore, when ANS activity is quantified and analyzed, it is
      usually from a point of convenience rather than from an understanding of its
      physiological basis. After a review of the experimental and therapeutic
      literatures exploring music and the ANS, a "Neurovisceral Integration"
      perspective on the interplay between the central and autonomic nervous systems is
      introduced, and the associated implications for physiological, emotional, and
      cognitive health are explored. The construct of heart rate variability is
      discussed both as an example of this complex interplay and as a useful metric for
      exploring the sometimes subtle effect of music on autonomic response. Suggestions
      for future investigations using musical interventions are offered based on this
      integrative account.

PMID- 21197138
TI  - Nucleophilic Aromatic Substitution, A Guided Inquiry Laboratory Experiment.
AB  - Inquiry-based learning is a unique student-centered alternative to traditional
      instruction. This form of active learning is ideal for the organic chemistry
      laboratory as it encourages critical thinking and hands on problem solving to
      complete an experiment. Electrophilic Aromatic Substitution is immediately
      associated with the undergraduate organic chemistry course. However, nucleophilic
      aromatic substitution is not. The N-arylation of aniline derivatives is a useful
      reaction for implementing nucleophilic aromatic substitution into the
      undergraduate curriculum. Under the framework of inquiry-based learning, a
      straightforward procedure has been developed for the undergraduate laboratory.
      This experiment explores the reaction rate of the nucleophilic aromatic
      substitution using various electrophiles. The reaction is conducted under
      microwave irradiation and the experiment is completed in one laboratory setting.

PMID- 21197137
TI  - Neural pathways for language in autism: the potential for music-based treatments.
AB  - Language deficits represent the core diagnostic characteristics of autism, and
      some of these individuals never develop functional speech. The language deficits
      in autism may be due to structural and functional abnormalities in certain
      language regions (e.g., frontal and temporal), or due to altered connectivity
      between these brain regions. In particular, a number of anatomical pathways that
      connect auditory and motor brain regions (e.g., the arcuate fasciculus, the
      uncinate fasciculus and the extreme capsule) may be altered in individuals with
      autism. These pathways may also provide targets for experimental treatments to
      facilitate communication skills in autism. We propose that music-based
      interventions (e.g., auditory-motor mapping training) would take advantage of the
      musical strengths of these children, and are likely to engage, and possibly
      strengthen, the connections between frontal and temporal regions bilaterally.
      Such treatments have important clinical potential in facilitating expressive
      language in nonverbal children with autism.

PMID- 21197139
TI  - Grouping of Brain MR Images via Affinity Propagation.
AB  - The human brain anatomy is extremely variable across individuals in terms of its
      size, shape, and structure patterning. In this paper, a novel method is proposed
      for grouping brain MR images into different patterns. This method adopts the
      affinity propagation methodology to partition a population of brain images into
      different clusters. In the affinity propagation method, the tissue-segmented and
      anatomically-parcellated images are used to define the similarity between brain
      images, in contrast to intensity-based similarity measurement used in previous
      methods. After clustering, in each cluster (called a sub-group) a representative
      exemplar image is identified as the single subject atlas for the sub-group.
      Meanwhile, all the subject images belonging to the same sub-group are identified.
      This method has been applied to the publicly available OASIS neuroimaging dataset
      that includes 414 subject brain MRI images. Experiments show that the method is
      able to group brain MR images into different patterns effectively.

PMID- 21197140
TI  - Automatic Detection of Previously-Unseen Application States for Deployment
      Environment Testing and Analysis.
AB  - For large, complex software systems, it is typically impossible in terms of time
      and cost to reliably test the application in all possible execution states and
      configurations before releasing it into production. One proposed way of
      addressing this problem has been to continue testing and analysis of the
      application in the field, after it has been deployed. A practical limitation of
      many such automated approaches is the potentially high performance overhead
      incurred by the necessary instrumentation. However, it may be possible to reduce
      this overhead by selecting test cases and performing analysis only in previously
      unseen application states, thus reducing the number of redundant tests and
      analyses that are run. Solutions for fault detection, model checking, security
      testing, and fault localization in deployed software may all benefit from a
      technique that ignores application states that have already been tested or
      explored.In this paper, we present a solution that ensures that deployment
      environment tests are only executed in states that the application has not
      previously encountered. In addition to discussing our implementation, we present
      the results of an empirical study that demonstrates its effectiveness, and
      explain how the new approach can be generalized to assist other automated testing
      and analysis techniques intended for the deployment environment.

PMID- 21197141
TI  - PRELIMINARY GASTROINTESTINAL STUDIES OF METHANOL EXTRACT OF INDIGOFERA PULCHRA
      WILLD IN RODENTS.
AB  - In this study, the effect of the methanol extract of Indigofera pulchra Willd.
      (Papillionaceae) was investigated against castor oil induced diarrheoa. Its
      effects on perfused isolated rabbit jejunum and guinea pig ileum were also
      evaluated. The extract produced a dose-dependent protection against the castor
      oil-induced diarrheoa in mice with the highest protection (100%), obtained at 200
      mgkg-1 comparable to that of loperamide (5 mgkg-1), a standard antidiarrhoeal
      drug. The extract (0.4 - 6.4 mgml-1) produced a concentration relaxation of the
      rabbit jejunum. However, no observable effect was noticed when the guinea pig
      ileum was treated. The extract blocked the contractile effect of acetylcholine (2
      * 10-8 gml-1) and histamine (4 * 10-7 gml-1) on both rabbit jejunum and guinea
      pig ileum. Phytochemical screening revealed the presence of flavonoids, tannins,
      saponins and steroids. The intraperitoneal median lethal dose (LD50) value for
      the extract was found to be 2154.0 mgkg-1. The results obtained revealed that the
      extract possesses pharmacologically active compounds with gastrointestinal
      relaxant and antidiarrhoeal activities and may possibly explain the use of the
      plant in traditional medicine for the treatment of gastrointestinal disorder.

PMID- 21197142
TI  - Gold(I)-Catalyzed Intermolecular Hydroamination of Allenes with Arylamines.
AB  - A mixture of (3)AuCl [3 = P(t-Bu)(2)o-biphenyl] and AgOTf catalyzes the
      intermolecular hydroamination of monosubstituted and 1,1- and 1,3-disubstituted
      allenes with primary and secondary arylamines.

PMID- 21197143
TI  - A Balanced Accuracy Fitness Function Leads to Robust Analysis using Grammatical
      Evolution Neural Networks in the Case of Class Imbalance.
AB  - Grammatical Evolution Neural Networks (GENN) is a computational method designed
      to detect gene-gene interactions in genetic epidemiology, but has so far only
      been evaluated in situations with balanced numbers of cases and controls. Real
      data, however, rarely has such perfectly balanced classes. In the current study,
      we test the power of GENN to detect interactions in data with a range of class
      imbalance using two fitness functions (classification error and balanced error),
      as well as data re-sampling. We show that when using classification error, class
      imbalance greatly decreases the power of GENN. Re-sampling methods demonstrated
      improved power, but using balanced accuracy resulted in the highest power. Based
      on the results of this study, balanced error has replaced classification error in
      the GENN algorithm.

PMID- 21197146
TI  - PREPARATION OF (S)-2-Allyl-2-methylcyclohexanone (Cyclohexanone, 2-methyl-2-(2
      propen-1-yl)-, (2S)-).

PMID- 21197147
TI  - Medical Conditions of Hazardous Drinkers and Drug Users in Primary Care Clinics
      in Cape Town, South Africa.
AB  - Research has identified a wide range of health conditions related to alcohol and
      drug use in studies conducted primarily in developed countries and in populations
      with severe alcohol and drug problems. Little is known about medical conditions
      in those with less severe alcohol and drug use in developing countries. We used
      WHO AUDIT and ASSIST screeners to identify hazardous drinking or drug use in
      public health clinics in Cape Town, South Africa, and included questions about
      doctor-diagnosed medical conditions. Using logistic regression we examined the
      relationship of medical conditions to hazardous alcohol, drug and tobacco use.
      Those with hazardous substance use had higher prevalence of many health
      conditions including tuberculosis. Hepatitis B, migraine, chronic bronchitis, and
      liver cirrhosis. Optimal treatment for some medical conditions may include
      treatment of underlying hazardous substance use, particularly use of drugs other
      than alcohol. In these populations, access to substance use treatment is limited
      and even brief interventions or advice may be useful.

PMID- 21197150
TI  - The Use of Garcinia Extract (Hydroxycitric Acid) as a Weight loss Supplement: A
      Systematic Review and Meta-Analysis of Randomised Clinical Trials.
AB  - The aim of this systematic review is to examine the efficacy of Garcinia extract,
      hydroxycitric acid (HCA) as a weight reduction agent, using data from randomised
      clinical trials (RCTs). Electronic and nonelectronic searches were conducted to
      identify relevant articles, with no restrictions in language or time. Two
      independent reviewers extracted the data and assessed the methodological quality
      of included studies. Twenty-three eligible trials were identified and twelve were
      included. Nine trials provided data suitable for statistical pooling. The meta
      analysis revealed a small, statistically significant difference in weight loss
      favouring HCA over placebo (MD: -0.88 kg; 95% CI: -1.75, -0.00). Gastrointestinal
      adverse events were twice as common in the HCA group compared with placebo in one
      included study. It is concluded that the RCTs suggest that Garcinia extracts/HCA
      can cause short-term weight loss. The magnitude of the effect is small, and the
      clinical relevance is uncertain. Future trials should be more rigorous and better
      reported.

PMID- 21197149
TI  - Pharmacological treatment of obesity in patients with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a common disorder affecting women of
      reproductive age and it is associated with increased cardiovascular risk. Obesity
      plays an important role in the pathogenesis of PCOS, and the majority of patients
      with PCOS are obese. Over the last 20 years, the prevalence of obesity has
      dramatically increased, with probable associated increase in PCOS. Weight
      reduction plays an integral part in the management of women with PCOS. In this
      paper, current available weight reduction therapies in the management of PCOS are
      discussed.

PMID- 21197148
TI  - Pharmacotherapies for obesity: past, current, and future therapies.
AB  - Past therapies for the treatment of obesity have typically involved
      pharmacological agents usually in combination with a calorie-controlled diet.
      This paper reviews the efficacy and safety of pharmacotherapies for obesity
      focusing on drugs approved for long-term therapy (orlistat), drugs approved for
      short-term use (amfepramone [diethylpropion], phentermine), recently withdrawn
      therapies (rimonabant, sibutamine) and drugs evaluated in Phase III studies
      (taranabant, pramlintide, lorcaserin and tesofensine and combination therapies of
      topiramate plus phentermine, bupropion plus naltrexone, and bupropion plus
      zonisamide). No current pharmacotherapy possesses the efficacy needed to produce
      substantial weight loss in morbidly obese patients. Meta-analyses support a
      significant though modest loss in bodyweight with a mean weight difference of 4.7
      kg (95% CI 4.1 to 5.3 kg) for rimonabant, 4.2 kg (95% CI 3.6 to 4.8 kg) for
      sibutramine and 2.9 kg (95% CI 2.5 to 3.2 kg) for orlistat compared to placebo at
      >=12 months. Of the Phase III pharmacotherapies, lorcaserin, taranabant,
      topiramate and bupropion with naltrexone have demonstrated significant weight
      loss compared to placebo at >=12 months. Some pharmacotherapies have also
      demonstrated clinical benefits. Further studies are required in some populations
      such as younger and older people whilst the long term safety continues to be a
      major consideration and has led to the withdrawal of several drugs.

PMID- 21197151
TI  - Pharmacological treatment of obesity in children and adolescents: present and
      future.
AB  - The prevalence of overweight and obesity is increasing in children and
      adolescents worldwide raising the question on the approach to this condition
      because of the potential morbidity, mortality, and economic tolls. Dietetic and
      behavioral treatments alone have only limited success; consequently, discussion
      on strategies for treating childhood and adolescent obesity has been promoted.
      Considering that our knowledge on the physiological systems regulating food
      intake and body weight is considerably increased, many studies have underlined
      the scientific and clinical relevance of potential treatments based on management
      of peripheral or central neuropeptides signals by drugs. In this paper, we
      analyze the data on the currently approved obesity pharmacological treatment
      suggesting the new potential drugs.

PMID- 21197153
TI  - A multiwavelength microflow cytometer.

PMID- 21197152
TI  - Gastric bypass promotes more lipid mobilization than a similar weight loss
      induced by low-calorie diet.
AB  - Background. Recently, we found large reductions in visceral and subcutaneous fat
      one month after gastric bypass (GBP), without any change in liver fat content.
      Purpose. Firstly to characterize weight loss-induced lipid mobilization after one
      month with preoperative low-calorie diet (LCD) and a subsequent month following
      GBP, and secondly, to discuss the observations with reference to our previous
      published findings after GBP intervention alone. Methods. 15 morbidly obese women
      were studied prior to LCD, at GBP, and one month after GBP. Effects on metabolism
      were measured by magnetic resonance techniques and blood tests. Results. Body
      weight was similarly reduced after both months (mean: -8.0 kg, n = 13). Relative
      body fat changes were smaller after LCD than after GBP (-7.1 +/- 3.6% versus -10
      +/- 3.2%, P = .029, n = 13). Liver fat fell during the LCD month (-41%, P = .001,
      n = 13) but was unaltered one month after GBP (+12%). Conclusion. Gastric bypass
      seems to cause a greater lipid mobilization than a comparable LCD-induced weight
      loss. One may speculate that GBP-altered gastrointestinal signalling sensitizes
      adipose tissue to lipolysis, promoting the changes observed.

PMID- 21197154
TI  - Adapting to Hard Times: Family Participation Patterns in Local Thrift Economies.
AB  - Using survey data from a western U.S. county (N = 595), we examined how lower,
      middle, and higher income families negotiate a period of economic stress-the
      closing of a major employer in the community-through their shopping patterns.
      Specifically, we examined their participation in local thrift economies such as
      yard sales and secondhand stores. We found that lower and middle income
      households shop more frequently at these venues. They also tend to shop more for
      furniture and clothing, whereas higher income households tend to shop for
      antiques and trinkets. These relationships varied across the type of thrift
      economy examined. Overall, findings support the argument that engagement in
      thrift economies may constitute one mechanism families use during periods of
      economic stress.

PMID- 21197156
TI  - Sensible Initialization Using Expert Knowledge for Genome-Wide Analysis of
      Epistasis Using Genetic Programming.
AB  - In human genetics it is now possible to measure large numbers of DNA sequence
      variations across the human genome. Given current knowledge about biological
      networks and disease processes it seems likely that disease risk can best be
      modeled by interactions between biological components, which may be examined as
      interacting DNA sequence variations. The machine learning challenge is to
      effectively explore interactions in these datasets to identify combinations of
      variations which are predictive of common human diseases. Genetic programming is
      a promising approach to this problem. The goal of this study is to examine the
      role that an expert knowledge aware initializer can play in the framework of
      genetic programming. We show that this expert knowledge aware initializer
      outperforms both a random initializer and an enumerative initializer.

PMID- 21197155
TI  - Alteration of intra-aneurysmal hemodynamics for flow diversion using enterprise
      and vision stents.
AB  - OBJECTIVE: Flow diversion is a novel concept for intracranial aneurysm treatment.
      The recently developed Enterprise Vascular Reconstruction Device (Codman
      Neurovascular, Raynham MA) provides easy delivery and repositioning. Although
      designed specifically for restraining coils within an aneurysm, this stent has
      theoretical effects on modifying flow dynamics, which have not been studied. The
      goal of this study was to quantify the effect of single and multiple self
      expanding Enterprise stents alone or in combination with balloon-mounted stents
      on aneurysm hemodynamics using computational fluid dynamics (CFD). METHODS: The
      geometry of a wide-necked, saccular, basilar trunk aneurysm was reconstructed
      from computed tomographic angiography images. Various combinations of 1-3 stents
      were "virtually" conformed to fit into the vessel lumen and placed across the
      aneurysm orifice. CFD analysis was performed to calculate hemodynamic parameters
      considered important in aneurysm pathogenesis and thrombosis for each model.
      RESULTS: The complex aneurysmal flow pattern was suppressed by stenting. Stent
      placement lowered average flow velocity in the aneurysm; further reduction was
      achieved by additional stent deployment. Aneurysmal flow turnover time, an
      indicator of stasis, was increased to 114-117% for single-stent, 127-128% for
      double-stent, and 141% for triple-stent deployment. Furthermore, aneurysmal wall
      shear stress (WSS) decreased with increasing number of deployed stents.
      CONCLUSION: This is the first study analyzing flow modifications associated with
      placement of Enterprise stents for aneurysm occlusion. Placement of 2-3 stents
      significantly reduced intra-aneurysmal hemodynamic activities, thereby increasing
      the likelihood of inducing aneurysm thrombotic occlusion.

PMID- 21197157
TI  - A Multivariate Logistical Model for Identifying the Compressive Sensitivity of
      Single Rat Tactile Receptors as Nanobiosensors.
AB  - Tactile sensation is a complex manifestation of mechanical stimuli applied to the
      skin. At the most fundamental level of the somatosensory system is the cutaneous
      mechanoreceptor. The objective here was to establish a framework for modeling
      afferent mechanoreceptor behavior as a nanoscale biosensor under dynamic
      compressive loads using multivariate regression techniques. A multivariate
      logistical model was chosen because the system contains continuous input
      variables and a singular binary-output variable corresponding to the nerve action
      potential. Subsequently, this method was used to quantify the sensitivity of ten
      rapidly adapting afferents from rat hairy skin due to the stimulus metrics of
      compressive stress, strain, their respective time derivatives, and interactions.
      In vitro experiments involving compressive stimulation of isolated afferents
      using pseudorandom and nonrepeating noise sequences were completed. An analysis
      of the data was performed using multivariate logistical regression producing odds
      ratios (ORs) as a metric associated with mechanotransduction. It was determined
      that cutaneous mechanoreceptors are preferentially sensitive to stress (mean
      OR(max) = 26.10), stress rate (mean OR(max) = 15.03), strain (mean OR(max) =
      12.01), and strain rate (mean OR(max) = 7.29) typically occurring within 7.3 ms
      of the nerve response. As a novel approach to receptor characterization, this
      analytical framework was validated for the multiple-input, binary-output neural
      system.

PMID- 21197158
TI  - Commercial Licensing of HIV-1 Protease: Applications of the NIH Research Tools
      Policy.
AB  - Licensing of the HIV-1 protease gene by the NIH Office of Technology Transfer
      (OTT) provides an example of the effective use of the principles of the NIH
      Research Tools Policy, which was designed to provide broad access to important
      biomedical technologies. The OTT licensing experience is presented in detail as
      it was applied to research reagents, diagnostics and drug development to thus
      enhance the overall development process for a wide variety of medical products.

PMID- 21197159
TI  - Listen to your drummer.

PMID- 21197160
TI  - The uses of art in the context of health and diversity.

PMID- 21197161
TI  - The development of children and the health of societies.

PMID- 21197162
TI  - Case 2: A persistent fever.

PMID- 21197163
TI  - Case 1: A long history of cough and dyspnea.

PMID- 21197166
TI  - The health of Canada's children. Part I: Canadian children's health in
      comparative perspective.
AB  - In the present article, the state of Canadian children's health is provided
      through an examination of scores on a set of key health indicators. National and
      provincial infant mortality rates show little recent improvement, and in the case
      of low birth weight rates, a worsening trend is evident. These health indicators
      are strongly related to income, and studies documenting these associations are
      reviewed. Compared with other wealthy nations, Canada performs poorly with regard
      to infant mortality rates and somewhat less so for low birth weight rates. For
      other health indicators and measures of the quality of the social determinants of
      children's health (such as poverty) and children's well-being, Canada's
      performance suggests that there are numerous areas for improvement.

PMID- 21197164
TI  - Is lead a concern in Canadian autistic children?
AB  - BACKGROUND: The Centers for Disease Control and Prevention (CDC) threshold for
      intervention for blood lead level (BLL) is greater than 0.48 MUmol/L, but new
      research suggests that there are adverse effects at any level of exposure.
      Children with autism are at increased risk for lead exposure and intoxication,
      and have later and more prolonged exposures because of exploratory oral
      behaviours and pica. OBJECTIVE: To estimate the mean BLL and prevalence of high
      BLL in a convenience sample of autistic children living in northern Alberta,
      based on the CDC threshold for intervention. METHODS: Children with autism were
      recruited from the clinics at the Glenrose Rehabilitation Hospital in Edmonton,
      Alberta. A complete blood count and differential, serum ferritin and BLL were
      requested after consent was obtained. Summary statistics were reported. For
      dichotomous outcomes, proportions were presented. Continuous outcomes for the two
      groups with a BLL of 0.1 MUmol/L or greater, or less than 0.1 MUmol/L were
      compared. RESULTS: None of the children tested had a BLL exceeding 0.48 MUmol/L.
      Nine children (19%) had BLLs of 0.1 MUmol/L or greater but less than 0.48
      MUmol/L, and 39 (81%) had BLLs of less than 0.1 MUmol/L. Those with a BLL of 0.1
      MUmol/L or greater had significantly more pica or oral exploratory behaviours.
      CONCLUSION: Children with autism in northern Alberta may not be at risk for
      elevated BLLs that exceed the CDC threshold for intervention. They should be
      screened for lead exposure risk factors and tested if there are risks, especially
      behaviours relating to pica and oral exploration of objects. Clinicians may need
      to further explore the reasons for low-level exposures to lead in the autistic
      population.

PMID- 21197167
TI  - Letter to the editor.

PMID- 21197168
TI  - Family-based treatment of children and adolescents with anorexia nervosa:
      Guidelines for the community physician.
AB  - Anorexia nervosa (AN) is a serious life-threatening illness that typically has
      its onset during the adolescent years. Evidence regarding the optimal treatment
      of AN in children and teenagers is growing; however, much remains unknown.
      Although current treatment approaches vary in Canada and elsewhere, the evidence
      to date indicates that family-based treatment (FBT) is the most effective
      treatment for children and teenagers with AN. A key component of the FBT model is
      that the parents are given the responsibility to return their child to physical
      health and ensure full weight restoration. An understanding of the basic
      principles and philosophy underlying FBT allows the physician to initiate
      elements of this evidence-based intervention to young patients with AN and their
      families.

PMID- 21197169
TI  - Sexting: Keeping teens safe and responsible in a technologically savvy world.

PMID- 21197170
TI  - Canadian Paediatric Surveillance Program 2009 quiz.

PMID- 21197173
TI  - Pain: putting the whole person at the centre.

PMID- 21197174
TI  - Can we identify people at risk of non-recovery after acute occupational low back
      pain? Results of a review and higher-order analysis.
AB  - PURPOSE: To identify prognostic factors in the literature that may predict a poor
      recovery from acute occupational low back pain (LBP). METHODS: Four international
      databases (Medline, CINAHL, EMBASE, and PsycINFO) were reviewed, searching all
      articles indexed up to November 2007 with the term low back pain combined with
      the terms prognostic, prospective, or cohort. Following application of inclusion
      criteria, 10 articles were found to be appropriate for data extraction. Each
      article was critically appraised by two independent reviewers. Statistical
      pooling was performed on any factor evaluated in at least three independent
      cohorts. RESULTS: Seven cohorts were identified, with a total sample size of
      2,484 subjects. Only three factors were followed in at least three cohorts and
      were therefore suitable for statistical pooling: female gender (OR=1.28, 95% CI:
      1.03-1.58); pain radiation (OR=1.37, 95% CI: 0.79-2.39); and previous history of
      back pain (OR=0.91, 95% CI: 0.52-1.60). There was significant heterogeneity
      within the female gender factor; compensation of subjects for study participation
      appeared to moderate its effect. CONCLUSION: After statistical pooling, only
      female gender achieved statistical significance as a prognostic factor for
      prolonged recovery. Further research is necessary to determine prognostic factors
      for non-recovery in acute LBP.

PMID- 21197175
TI  - Diagnostic accuracy and association to disability of clinical test findings
      associated with patellofemoral pain syndrome.
AB  - PURPOSE: To investigate the diagnostic accuracy and association to disability of
      selected functional findings or physical examination tests for patellofemoral
      pain syndrome (PFPS) in patients with anterior knee pain. METHODS: A sample of 76
      consecutive patients with anterior knee pain was further subdivided into PFPS and
      other diagnoses. Routine physical examination tests were examined in a
      prospective, consecutive-subjects design for a cohort of patients with anterior
      knee pain. Diagnostic accuracy findings, including sensitivity, specificity,
      positive (PPV) and negative (NPV) predictive value, and positive (LR+) and
      negative (LR-) likelihood ratios, were calculated for each test. PPV and NPV
      reflect the percentage of time of positive or a negative test (respectively)
      accurately captures the diagnosis of the condition. LR+ and LR- reflect
      alterations in post-test probability when the test is positive or negative
      (respectively). Lastly, associations to disability (International Knee
      Documentation Committee (IKDC) subjective form) were calculated for each clinical
      finding. RESULTS: Diagnostic accuracy analyses of individual functional
      assessment and situational phenomena suggest that the strongest diagnostic test
      is pain encountered during resisted muscle contraction of the knee (PPV=82%;
      LR+=2.2; 95% CI: 0.99-5.2). Clusters of test findings were substantially more
      diagnostic, with any two of three positive findings of muscle contraction, pain
      during squatting, and pain during palpation yielding the following values:
      PPV=89%; LR+=4.0 (95% CI: 1.8-10.3). No individual or clustered test findings
      were significantly associated with the IKDC score. CONCLUSION: Combinations of
      functional assessment tests and situational phenomena are diagnostic for PFPS and
      may serve to rule in and rule out the presence of PFPS. Single findings are not
      related to disability scores (IKDC).

PMID- 21197176
TI  - Effects of physical activity on cancer survival: a systematic review.
AB  - PURPOSE: Physical activity (PA) has been suggested to help increase the survival
      of individuals with cancer. The objective of this review was to systematically
      evaluate and summarize the available evidence investigating the effect of PA on
      the survival of individuals with cancer. METHODS: Electronic databases (CINAHL,
      EMBASE, and MEDLINE) were systematically searched for randomized controlled
      trials and cohort studies. Selected studies were assessed by two independent
      investigators for methodological quality, using the PEDro scale. RESULTS: Ten
      prospective cohort studies met the inclusion criteria. Quality-assessment scores
      averaged 5/10 on the PEDro scale, with two articles obtaining a score of 6/10.
      The majority of studies found that individuals participating in higher levels of
      physical activity had a reduced risk of cancer-related mortality. This trend was
      observed specifically for breast, colon, and colorectal cancers. On average, it
      appears that engaging in higher levels of metabolic equivalent hours per week may
      help to improve survival rates among individuals diagnosed with cancer.
      CONCLUSION: Patients diagnosed with cancer demonstrated a trend toward increased
      survival with greater levels of PA. However, because only prospective cohort
      studies were included in the study, the conclusions drawn should be regarded with
      caution.

PMID- 21197177
TI  - Changes in activities of wives caring for their husbands following stroke.
AB  - PURPOSE: The purpose of this study was to explore the perspectives of caregivers
      of persons with stroke with respect to their own physical activity. METHODS: A
      qualitative, descriptive approach was used to study 10 caregivers of persons with
      stroke, recruited from a stroke exercise class in a large urban rehabilitation
      facility. Caregivers participated in individual, semi-structured interviews that
      were audiotaped, transcribed verbatim, and analysed using a constant comparative
      method. An inductive, iterative approach was applied to determine the codes and
      themes. RESULTS: Four main themes were identified: change in role, change in
      activity, barriers to activity and health, and change in meaning of activity.
      Barriers to activity included guilt, time, and energy. Participants revealed that
      activity became more therapeutic after stroke and that participants preferred
      purposeful, functional, and partnered activities. CONCLUSIONS: These findings
      emphasize the importance of the husband-wife dyad and of movement toward a family
      centred care approach. Education should be provided to caregivers regarding their
      role, barriers, and health-promoting activities. Future research should focus on
      determining appropriate physical-activity programmes for caregivers as well as on
      evaluating implementation of partnered exercise programmes for caregivers and
      persons with stroke.

PMID- 21197178
TI  - Clinician's commentary.

PMID- 21197179
TI  - Inter-professional collaboration: passing fad or way of the future?

PMID- 21197180
TI  - A pilot study of the incidence of post-thoracotomy pulmonary complications and
      the effectiveness of pre-thoracotomy physiotherapy patient education.
AB  - PURPOSE: To estimate the incidence and examine the pattern of post-thoracotomy
      pulmonary complications (PPC) that are amenable to physiotherapy treatment and to
      estimate the effect size of a pre-thoracotomy physiotherapy education session
      compared to no preoperative physiotherapy for reducing PPC. METHODS: Forty-two
      patients undergoing thoracotomy participated in this two-group retrospective
      prospective cohort study. The preop group (n=22) received physiotherapy education
      prior to surgery and the no preop group (n=20) did not receive preoperative
      physiotherapy education. Chest radiographs were examined for PPC for 5 days
      postoperatively. Incidences of PPC were determined. The effect size was based on
      a grand count of PPC. RESULTS: The 5-day incidence of atelectasis, collapse,
      consolidation, and other complications was 85.0%, 39.0%, 31.7%, and 38.1%,
      respectively. Patterns of PPC showed large increases at days 2 and 3. The effect
      size for pre-thoracotomy physiotherapy education was zero. CONCLUSIONS: In our
      sample, incidence of PPC was high and did not substantially differ based on
      whether or not preoperative education was provided.

PMID- 21197181
TI  - Intradisciplinary clinical education for physiotherapists and physiotherapist
      assistants: a pilot study.
AB  - PURPOSE: This study investigated the perceived impact of a paired 5-week clinical
      placement on physiotherapy (PT) and physiotherapist assistant (PTA) students'
      skills. Students were supervised by a PT clinical instructor (CI), and a
      collaborative peer-coaching model was used. METHOD: Three pairs of PT and PTA
      students participated in concurrent paired placements incorporating the concepts
      of reciprocal peer coaching and the 2:1 model of supervision. Qualitative data
      were gathered using pre- and post-placement interviews and the participants'
      journals. RESULTS: The participants reported that using this clinical education
      model increased their self-directed learning. This outcome was anticipated by the
      researchers with the incorporation of the 2:1 model of supervision. The post
      placement interviews also indicated that there was informal teaching among
      students, as expected from the integration of reciprocal peer coaching.
      Participants reported an improvement in the students' competencies in
      communication, consultation, and assignment of tasks within the physiotherapy
      team. The students further reported an increase in their confidence with regard
      to their respective roles and an improvement in their ability to work effectively
      within the physiotherapy team. CONCLUSION: As indicated by the comments and
      reviews of the participants, pairing PT and PTA students on clinical placements
      and incorporating a collaborative peer-coaching model can result in improvements
      in the students' skills in communication, consultation, and assignment of tasks.

PMID- 21197182
TI  - Informing your practice with reviews published by the cochrane back review group:
      conservative interventions for neck and back pain.

PMID- 21197183
TI  - Fences.

PMID- 21197184
TI  - National practice benchmark: 2010 report on 2009 data.
AB  - PURPOSE: Oncology practices continue to experience economic pressures as costs
      rise, numbers of patients increase, and reimbursements from payers remain flat or
      decrease. Many practices have responded to these challenges by examining business
      processes and making changes to improve efficiency and decrease costs. The
      National Practice Benchmark is a national survey of community oncology practices
      that provides data for practices to use in managing today's challenging practice
      environment. METHODS: Oncology practices were invited to participate in an online
      benchmarking survey. One hundred eighty-nine practices from 44 states responded
      to the survey, and demographic, operational, and financial data were collected
      for calendar year 2009 or the most recently completed fiscal year. RESULTS: Data
      from 2009 were compiled and compared with previously collected 2007 and 2008
      data. The data reveal that total revenue has increased by approximately 6% per
      year over this 3-year period. During the same period, however, cost of drugs
      increased dramatically: 13.5% increase from 2007 to 2008 and 16% from 2008 to
      2009. Total practice expense increased at virtually the same level as drug costs
      in 2008 and was flat for 2009. CONCLUSION: Survey results indicate an overall
      lowering of practice expenses even as cost of drugs continues to rise, and are
      consistent with the slight increase in the number of new patients per full-time
      equivalent hematology/oncology physician. These measures indicate an overall
      increase in service delivery efficiency and adaptation by many practices to the
      changing practice environment.

PMID- 21197185
TI  - Impact of shifting from office- to hospital-based treatment facilities on the
      administration of intraperitoneal chemotherapy for ovarian cancer.
AB  - INTRODUCTION: Cancer chemotherapy in the United States has been delivered mostly
      in an office-based setting since the late 1980s. However, in the past 5 years,
      more patients have been treated in hospitals as a result of reimbursement
      changes. Intraperitoneal (IP) chemotherapy for ovarian cancer has been similarly
      affected. This report examines changes in care of women treated with IP
      chemotherapy in an office- versus hospital-based setting. METHODS: Over 10 years,
      140 women with ovarian cancer were identified as candidates for IP chemotherapy.
      Of these patients, 92 were treated in an oncology-dedicated infusion center in
      the office of a physicians' group; 48 were treated in a local hospital. Location
      was determined based on insurance coverage and reimbursement. Data collected
      included demographics, number of treatment cycles completed, length of each
      treatment, and adverse events. RESULTS: The age and ethnicity of patients treated
      in the office versus hospital were similar. All six doses of intravenous IP
      chemotherapy were completed by 73 (79%) of 92 patients treated in the office
      versus 23 (48%) of 48 patients treated in the hospital (P < .001). The time of
      each infusion was longer in the hospital-versus office-based setting (P < .001).
      There were more adverse events associated with treatment in the hospital.
      CONCLUSION: IP chemotherapy is associated with worse outcomes in the hospital-
      compared with office-based setting. The reason seems to involve a relative lack
      of resources directed specifically to chemotherapy administration. If current
      reimbursement trends continue, this could result in decreased survival for women
      with ovarian cancer.

PMID- 21197186
TI  - Commentary: when it comes to chemotherapy, location matters.

PMID- 21197187
TI  - Coverage policy development for personalized medicine: private payer perspectives
      on developing policy for the 21-gene assay.
AB  - PURPOSE: Personalized medicine is changing oncology practice and challenging
      decision making. A key challenge is the limited clinical evidence for many
      personalized medicine technologies. We describe the strategies private payers
      employed to develop coverage policy for personalized medicine using the example
      of the 21-gene assay in breast cancer. METHODS: We examined the coverage policies
      of six private payers for the 21-gene assay. We then interviewed senior
      executives (n = 7) from these payers to elucidate factors informing coverage
      decisions. We additionally focused on the timing of payer decisions compared with
      the timing of evidence development, measured by publication of primary studies
      and relevant clinical guidelines. RESULTS: The 21-gene assay became commercially
      available in 2004. The interviewed payers granted coverage between 2005 and 2008.
      Their policies varied in structure (eg, whether prior authorization was
      required). All payers reported clinical evidence as the most important factor in
      decision making, but all used some health care system factors (eg, physician
      adoption or medical society endorsement) to inform decision making as well.
      Payers had different perceptions about the strength of clinical evidence at the
      time of the coverage decision. CONCLUSION: Coverage of the 21-gene assay is
      currently widespread, but policies differ in timing and structure. A key approach
      private payers use to develop coverage policies for novel technologies is
      considering both clinical evidence and health care system factors. Policy
      variation may emerge from the range of factors used and perception of the
      evidence. Future research should examine the role of health care system factors
      in policy development and related policy variations.

PMID- 21197188
TI  - American society of clinical oncology clinical practice guideline update on
      adjuvant endocrine therapy for women with hormone receptor-positive breast
      cancer.
AB  - ASCO's technology assessment of the use of aromatase inhibitors in the adjuvant
      setting was last updated in 2004. ASCO's Update Committee on Aromatase Inhibitors
      reconvened in May 2009 to update this guideline.

PMID- 21197189
TI  - Ethical challenges: oncologists' role in immigrant health care.
AB  - As health care and immigration policies evolve, oncologists may be faced with
      challenges regarding care for undocumented immigrants, and must stay abreast of
      changes in federal and state legal statutes as well as medical ethics guidelines.

PMID- 21197190
TI  - Clinical research site infrastructure and efficiency.
AB  - Increasing efficiency in the clinical trials development process ensures a
      vibrant clinical trials system that makes best use of resources, and keeps pace
      with scientific discoveries in the field of cancer research.

PMID- 21197191
TI  - How to implement change in practice.
AB  - Learn what it takes to overcome the status quo and implement change because
      stagnation can jeopardize the future of your practice.

PMID- 21197192
TI  - A paleontology primer for oncologists.
AB  - Just as a blazing meteor wiped out large dinosaurs, health care reform may
      eliminate solo practitioners.

PMID- 21197193
TI  - The dinosaur is extinct: the demise of solo medical oncology practice in the
      United States.
AB  - Evolution is brought about by subtle environmental pressures over time or by a
      cataclysmic extinction event. The latter is the case for the solo medical
      oncologist, with the event being the Medicare Modernization Act of 2003.

PMID- 21197194
TI  - Reducing cancer costs and improving quality through collaboration with payers: a
      proposal from the Florida society of clinical oncology.
AB  - One of Florida's largest private payers has retained an outside consulting firm
      to develop a program to reduce cancer care spending, which could seriously limit
      the ability of oncology practices in Florida to provide quality care to their
      patients.

PMID- 21197195
TI  - Role of oncology clinical pharmacists in light of the oncology workforce study.
AB  - To date, the information published regarding workforce implications has focused
      on physicians, nurse practitioners, and physician assistants. But oncology
      clinical pharmacists also can assist with direct patient care and patient
      education activities.

PMID- 21197196
TI  - Tail docking and ear cropping - A comment.

PMID- 21197198
TI  - Medical science and society.

PMID- 21197199
TI  - Veterinary medical ethics: An ethicist's commentary on the double standard in
      veterinary medicine.

PMID- 21197200
TI  - The epidemiology of bovine respiratory disease: What is the evidence for
      predisposing factors?
AB  - Bovine respiratory disease (BRD) is the most costly disease of beef cattle in
      North America. It is multi-factorial, with a variety of physical and
      physiological stressors combining to predispose cattle to pneumonia. However,
      efforts to discern which factors are most important have frequently failed to
      establish definitive answers. Calves are at highest risk shortly after transport.
      Risk factors include purchasing from sale barns and commingling. It is unclear
      whether or not these practices increase susceptibility, increase exposure, or are
      proxies for poor management. Lighter-weight calves appear to be at greater risk,
      although this has not been consistent. Persistent infection (PI) with bovine
      virus diarrhea virus increases BRD occurrence, but it is unclear if PI calves
      affect other cattle in the feedlot. The complexity of BRD has made it difficult
      to define involvement of individual factors. Stressors may play a role as
      "necessary but not sufficient" components, requiring additive effects to cause
      disease.

PMID- 21197201
TI  - Epidemiology of equine sarcoids in horses in western Canada.
AB  - Sarcoids are the most common tumor of the equine skin but only 1 study describing
      the epidemiology of sarcoids in Canadian horses has been published. The records
      of 5 veterinary diagnostic laboratories in western Canada were searched to
      identify submissions of sarcoids from horses. The submission records and
      diagnostic reports of 802 separate submissions of equine sarcoids were reviewed
      for age, breed, and gender of the horse and the number, location, and clinical
      type of sarcoid. From these records, the 307 submissions to laboratories in
      Saskatchewan were compared to a reference group to test for breed and gender
      predisposition. Based on clinical history and lesion descriptions, 5 clinical
      types of sarcoids were identified. Horses of various ages and 23 equine breeds
      were affected; donkeys were over-represented. Polymerase chain reaction (PCR) for
      the bovine papillomavirus (BPV) DNA was performed on formalin-fixed paraffin
      embedded tissues from a stratified subset of 96 of the different clinical types;
      BPV2 was present in 60 of 74 (81%) for which a PCR product was obtained. Unlike
      other areas in the world, in western Canada, equine sarcoids are most commonly
      associated with BPV type 2.

PMID- 21197202
TI  - Immunohistochemical expression of vascular endothelial growth factor and vascular
      endothelial growth factor receptor-2 in canine simple mammary gland
      adenocarcinomas.
AB  - The expression of 5 markers associated with angiogenesis, proliferation, and
      apoptosis was studied in 26 canine simple mammary gland adenocarcinomas (SMGAs).
      The adenocarcinomas were graded histologically, and tissue sections were
      immunohistochemically stained for the expression of vascular endothelial growth
      factor (VEGF), VEGF receptor-2 (VEGFR-2), intra-tumor microvessel density, and
      tumor proliferation (PI) using antibodies against VEGF, VEGFR-2, von Willebrand
      factor, and Ki-67 antigen, respectively. Apoptotic indices (AI) were determined
      by an apoptosis assay. Markers VEGF and VEGFR-2 were detected in 96% and 100% of
      SMGAs, respectively. A high correlation between histologic grade and PI (r =
      0.73), a moderate correlation between VEGF and histologic grade (r = 0.33), and
      between VEGF and PI (r = 0.42) were found. There was a significant difference in
      median PI among the 3 histologic grade groups (r < 0.05). Vascular endothelial
      growth factor may stimulate tumor cell proliferation through an autocrine loop,
      since VEGF and VEGFR-2 were expressed in most tumors.

PMID- 21197203
TI  - Evaluation and delivery of domestic animal health services in remote communities
      in the Northwest Territories: A case study of status and needs.
AB  - Domestic animal health services are supplied to communities in Canada's Northwest
      Territories (NT) in diverse ways, including private veterinary practices in 2 of
      33 communities, and by mail-order, fly-in, free clinics, and a government
      coordinated lay vaccinator program in some of the other 31 communities. We
      evaluated delivery, needs, and potential uptake of domestic animal health
      services in the Sahtu Settlement Area, NT by offering free clinics for 225 dogs
      in 2008 and 2009; and administered questionnaires to 42 dog owners and 67
      students in 2008. Owners indicated that 20% of dogs were neutered, 37% had had
      rabies vaccinations, and 29% had been dewormed. Physical examination of dogs
      demonstrated that 54% were "thin" and 4% were "emaciated." Owners and youth
      showed a range of attitudes toward dogs and supported improved domestic animal
      health services. Future services need to build on existing programs and
      collaborate with communities to ensure relevance, ownership, and sustainability.

PMID- 21197204
TI  - Heart disease in cattle with clinical signs of heart failure: 59 cases.
AB  - This retrospective study identified clinical signs, underlying cardiac
      conditions, blood findings, echocardiographic findings, and prognosis for 59
      cattle with clinical signs of congestive heart failure. Signalment; history;
      clinical signs; clinicopathologic, echocardiographic, and radiographic findings;
      and treatment were determined by reviewing medical records. Follow-up information
      was obtained by telephone conversation with owners. Most patients were
      tachycardic (n = 50), and tachypneic (n = 55). Pericarditis of traumatic origin
      (n = 21), by extension from pleuritis (n = 3), or of idiopathic origin (n = 1)
      was diagnosed in 25 cases. Other diagnoses were congenital heart defect (n = 13),
      cardiomyopathy (n = 9), bacterial endocarditis (n = 7), and neoplasm (n = 5).
      Twelve cases (20%) were discharged. Long-term survival was good in 2 out of 3
      cases treated by pericardiostomy. The prognosis is poor in cases of heart failure
      in cattle and deaths within 1 mo (n = 3) or between 1 to 3 mo after discharge (n
      = 3) were common in cases for which follow-up was available (n = 8).

PMID- 21197205
TI  - Azoospermia in an 8-month-old boar due to bilateral obstruction at the
      testis/epididymis interface.
AB  - An 8-month-old Yorkshire boar was presented for apparent azoospermia. Two semen
      collections also revealed azoospermia. Ultrasonographic examination of the gonads
      revealed bilateral caput epididymal dilatation and anechoic fluid within the
      tubules. Because a testicular biopsy revealed normal spermatogenesis, an outflow
      tract obstruction was suspected. Multiple sperm granulomas were found within the
      parenchyma of both testes at necropsy.

PMID- 21197206
TI  - One-lung ventilation using a wire-guided endobronchial blocker for thoracoscopic
      pericardial fenestration in a dog.
AB  - Instead of a conventional double lumen tube, an Arndt wire-guided endobronchial
      blocker was used to achieve one-lung ventilation in a dog undergoing
      thoracoscopic pericardiectomy. Overall, lung separation was easy to perform and
      surgical conditions for the creation of a pericardial window were adequate.
      Special ventilation strategies were applied.

PMID- 21197207
TI  - Botulism in 2 urban dogs.
AB  - Two dogs from the same owner were referred for ascending weakness and paresis of
      2 to 3 days duration. Electromyography and electroneurography determined that
      there were normal F-waves, decreased compound action potential, and decreased
      activity on repetitive nerve stimulation. These findings were valuable in
      diagnosing botulism in the dogs.

PMID- 21197208
TI  - Accidental salinomycin intoxication in calves.
AB  - Twenty-four 10- to 16-week-old calves in a dairy herd in Birjand, Iran,
      inadvertently received an excessive dose of salinomycin mixed with barley grain.
      There was 58% mortality within 10 d. The calves had high serum AST, LDH, and CK
      activities; histopathologic lesions in myocardium, liver, and kidneys; and
      clinical signs associated with acute and congestive heart failure.

PMID- 21197209
TI  - Feline porphyria associated with anemia, severe hepatic disease, and renal
      calculi.
AB  - A 13-year-old, neutered male domestic cat presented with signs of weight loss,
      anemia, and hepatomegaly. Pathognomonic signs of porphyria were identified.
      Charcoal-like renal calculi and severe liver changes were observed, neither of
      which has been previously reported in association with feline porphyria.

PMID- 21197210
TI  - A case of facial deformity due to bilateral developmental maxillary cheek teeth
      displacement in an adult horse.
AB  - A 7-year-old mare presented with facial deformities associated with oral
      discomfort and weight loss was found to have bilateral, palatal, developmental
      displacements of the maxillary 08s, with secondary diastema. Following repulsion
      of both displaced teeth, the horse regained weight and resumed training. Bony
      deformities remained visible 9 mo after discharge.

PMID- 21197211
TI  - Granulosa theca cell tumor with erythrocytosis in a llama.
AB  - A 2.5-year-old, female llama with weight loss and lethargy had a packed cell
      volume (PCV) of 45% which increased to 57% over 3 wk. Transrectal ultrasonography
      revealed a mass of mixed echogenicity involving the right ovary, which was
      removed. A histopathological diagnosis of granulosa theca cell tumor was made.
      This is the first report of its kind in a llama.

PMID- 21197212
TI  - Bottom-up communication.

PMID- 21197213
TI  - Walking the tightrope.

PMID- 21197214
TI  - Engineering towards functional tissues and organs.

PMID- 21197215
TI  - Amphibians as research models for regenerative medicine.
AB  - The ability to regenerate bone across a critical size defect would be a marked
      clinical advance over current methods for dealing with such structural gaps.
      Here, we briefly review the development of limb bones and the mandible, the
      regeneration of urodele limbs after amputation, and present evidence that urodele
      and anuran amphibians represent a valuable research model for the study of
      segment defect regeneration in both limb bones and mandible.

PMID- 21197217
TI  - Vascular organogenesis: dream or reality?

PMID- 21197216
TI  - Strategies for organ level tissue engineering.
AB  - The field of tissue engineering has made considerable strides since it was first
      described in the late 1980s. The advent and subsequent boom in stem cell biology,
      emergence of novel technologies for biomaterial development and further
      understanding of developmental biology have contributed to this accelerated
      progress. However, continued efforts to translate tissue-engineering strategies
      into clinical therapies have been hampered by the problems associated with
      scaling up laboratory methods to produce large, complex tissues. The significant
      challenges faced by tissue engineers include the production of an intact
      vasculature within a tissue-engineered construct and recapitulation of the size
      and complexity of a whole organ. Here we review the basic components necessary
      for bioengineering organs-biomaterials, cells and bioactive molecules-and discuss
      various approaches for augmenting these principles to achieve organ level tissue
      engineering. Ultimately, the successful translation of tissue-engineered
      constructs into everyday clinical practice will depend upon the ability of the
      tissue engineer to "scale up" every aspect of the research and development
      process.

PMID- 21197218
TI  - Development, characterization and clinical use of a biodegradable composite
      scaffold for bone engineering in oro-maxillo-facial surgery.
AB  - We have developed a biodegradable composite scaffold for bone tissue engineering
      applications with a pore size and interconnecting macroporosity similar to those
      of human trabecular bone. The scaffold is fabricated by a process of particle
      leaching and phase inversion from poly(lactideco-glycolide) (PLGA) and two
      calcium phosphate (CaP) phases both of which are resorbable by osteoclasts; the
      first a particulate within the polymer structure and the second a thin ubiquitous
      coating. The 3-5 MUm thick osteoconductive surface CaP abrogates the putative
      foreign body giant cell response to the underlying polymer, while the internal
      CaP phase provides dimensional stability in an otherwise highly compliant
      structure. The scaffold may be used as a biomaterial alone, as a carrier for
      cells or a three-phase drug delivery device. Due to the highly interconnected
      macroporosity ranging from 81% to 91%, with macropores of 0.8~1.8 mm, and an
      ability to wick up blood, the scaffold acts as both a clot-retention device and
      an osteoconductive support for host bone growth. As a cell delivery vehicle, the
      scaffold can be first seeded with human mesenchymal cells which can then
      contribute to bone formation in orthotopic implantation sites, as we show in
      immune-compromised animal hosts. We have also employed this scaffold in both
      lithomorph and particulate forms in human patients to maintain alveolar bone
      height following tooth extraction, and augment alveolar bone height through
      standard sinus lift approaches. We provide a clinical case report of both of
      these applications; and we show that the scaffold served to regenerate sufficient
      bone tissue in the wound site to provide a sound foundation for dental implant
      placement. At the time of writing, such implants have been in occlusal function
      for periods of up to 3 years in sites regenerated through the use of the
      scaffold.

PMID- 21197219
TI  - Advances in musculoskeletal tissue engineering: moving towards therapy.
AB  - Skeletal muscle can self-repair, but is unable to restore significant tissue
      loss, as consequence of trauma, congenital defects, tumor ablation or
      denervation. Intramuscular injection of autologous or allogenic derived myogenic
      cells (namely satellite cells and myoblasts) did not lead to efficient
      regeneration because of poor cell retention and survival, as well as
      immunorejection. In the last decade, tissue engineering looked at overcoming
      these problems by investigating alternative treatment options, i.e., the
      suspension of myogenic precursors in temporary matrix, formed by biodegradable
      and biocompatible materials. This approach allows to engineer custom
      architectured preconditioned implants, and locally deliver paracrine factors.This
      article reviews current and potential strategies for the repair of damaged muscle
      and suggests some innovative approaches for the translation to the clinical
      setting.

PMID- 21197220
TI  - Injectable in situ forming biodegradable chitosan-hyaluronic acid based hydrogels
      for adipose tissue regeneration.
AB  - An injectable, biodegradable and glucose-responsive hydrogel derived from natural
      polysaccharide derivatives was synthesized to deliver adipogenic factor of
      insulin in vitro for adipose tissue engineering. The biodegradable hydrogel based
      N-succinyl-chitosan (SCS) and aldehyde hyaluronic acid (AHA) with covalently
      conjugated glucose oxidase and catalase. The gelation is attributed to the Schiff
      base reaction between amino and aldehyde groups of SCS and AHA, respectively. The
      morphologies and compressive modulus of the freeze-dried hydrogels demonstrated
      that the incorporated insulin and enzymes results in the formation of a tighter
      network structure in composite hydrogels. The immobilized enzymes triggered
      conversion of glucose reduces the pH value of the microenvironment, and results
      in hydrolysis and increasing swelling of the network basing on Schiff-base cross
      linking. The pH inside the hydrogel, kept in PBS solution at pH 7.4 and 37
      degrees C, linearly dropped from 7.40 to 7.17 during 4 h of initial period, then
      slowly increased to 7.36 after 24 h. Correspondingly, the swelling ratio
      increased from 20.8 to 28.6 at 37 degrees C in PBS with 500 mg/dL glucose. In PBS
      buffer with 500 mg/dL glucose, about 10.8% of insulin was released from the
      hydrogel after 8 h of incubation while upon observation. The results demonstrated
      that the adipogenic factor of insulin would be released from this biodegradable
      hydrogel device into the local microenvironment in a controlled fashion by the
      swelling of hydrogel network. These preliminary studies indicate that the
      biodegradable and glucose-responsive hydrogel may have potential uses in adipose
      tissue engineering applications.

PMID- 21197221
TI  - Interactions between human osteoblasts and prostate cancer cells in a novel 3D in
      vitro model.
AB  - Cell-cell and cell-matrix interactions play a major role in tumor morphogenesis
      and cancer metastasis. Therefore, it is crucial to create a model with a
      biomimetic microenvironment that allows such interactions to fully represent the
      pathophysiology of a disease for an in vitro study. This is achievable by using
      three-dimensional (3D) models instead of conventional two-dimensional (2D)
      cultures with the aid of tissue engineering technology. We are now able to better
      address the complex intercellular interactions underlying prostate cancer (CaP)
      bone metastasis through such models. In this study, we assessed the interaction
      of CaP cells and human osteoblasts (hOBs) within a tissue engineered bone (TEB)
      construct. Consistent with other in vivo studies, our findings show that
      intercellular and CaP cell-bone matrix interactions lead to elevated levels of
      matrix metalloproteinases, steroidogenic enzymes and the CaP biomarker, prostate
      specific antigen (PSA); all associated with CaP metastasis. Hence, it highlights
      the physiological relevance of this model. We believe that this model will
      provide new insights for understanding of the previously poorly understood
      molecular mechanisms of bone metastasis, which will foster further translational
      studies, and ultimately offer a potential tool for drug screening.

PMID- 21197222
TI  - The relationship between nephron number, kidney size and body weight in two
      inbred mouse strains.
AB  - While some reports in humans have shown that nephron number is positively
      correlated with height, body weight or kidney weight, other studies have not
      reproduced these findings. To understand the impact of genetic and environmental
      variation on these relationships, we examined whether nephron number correlates
      with body weight, kidney planar surface area, or kidney weight in two inbred
      mouse strains with contrasting kidney sizes but no overt renal pathology: C3H/HeJ
      and C57BL/6J. C3H/HeJ mice had smaller kidneys at birth and larger kidneys by
      adulthood, however there was no significant difference in nephron number between
      the two strains. We did observe a correlation between kidney size and body weight
      at birth and at adulthood for both strains. However, there was no relationship
      between nephron number and body weight or between nephron number and kidney size.
      From other studies, it appears that a greater than two-fold variation is required
      in each of these parameters in order to demonstrate these relationships,
      suggesting they are highly dependent on scale. Our results are therefore not
      surprising since there was a less than two-fold variation in each of the
      parameters examined. In summary, the relationship between nephron number and body
      or kidney size is most likely to be demonstrated when there is greater phenotypic
      variation either from genetic and/or environmental factors.

PMID- 21197223
TI  - Evaluation of a veterinary-based syndromic surveillance system implemented for
      swine.
AB  - Practicing veterinarians play an important role in detecting the initial outbreak
      of disease in animal populations. A pilot study was conducted to determine the
      feasibility of a veterinary-based surveillance system for the Ontario swine
      industry. A total of 7 practitioners from 5 clinics agreed to submit information
      from July 1, 2007 to June 30, 2008. The surveillance program was evaluated in
      terms of timeliness, compliance, geographic coverage, and data quality. Our study
      showed that the veterinary-based surveillance system was acceptable to
      practitioners and produced useful data. The program obtained information from 25%
      of pig farms in Ontario during this time period. However, better communication
      with practitioners, more user-friendly recording systems that can be adapted to
      each clinic's management system, active involvement of the clinics' technical
      personnel, and the use of financial incentives may help to improve compliance and
      timeliness.

PMID- 21197224
TI  - Pathogenesis of systemic Mycobacterium avium infection in pigs through
      histological analysis of hepatic lesions.
AB  - Mycobacterium avium causes systemic infections through primary intestinal lesions
      in pigs. However, its pathogenesis is not well understood. The aim of this study
      was to confirm the effects on swine after enteral infection. One hundred and
      twelve pigs with hepatic lesions infected with M. avium were used in this study.
      We investigated the involvement of other organs and the distribution of hepatic
      lesions in the lobular structure. Most lesions involved the mesenteric lymph
      nodes. Hepatic lymph nodes were the secondary nodes involved. In 74 cases
      (66.1%), the hepatic lesions were predominantly distributed in the portal tract
      of the affected livers. The other 38 cases (33.9%) showed granulomatous lesions
      in the hepatic lobule. Many cases showed interface hepatitis. There was a
      significant relationship between focal lesions within hepatic lobule and splenic
      lesions. These findings suggest that granulomatous lesions formed in hepatic
      lobules upon establishment of bacteremia in pigs systemically infected with M.
      avium.

PMID- 21197225
TI  - A clinical field trial to evaluate the efficacy of vaccination in controlling
      Salmonella infection and the association of Salmonella-shedding and weight gain
      in pigs.
AB  - A clinical field trial was performed to determine the effectiveness of an
      autogenous Salmonella Typhimurium bacterin compared with a commercial live S.
      Choleraesuis vaccine in pigs. The association between Salmonella shedding and
      weight gain was also investigated. Nine cohorts of weaned pigs, (330 to 350 pigs
      per cohort), were randomly assigned to 1 of 3 treatment groups (injection with S.
      Typhimurium bacterin, vaccination via water with S. Choleraesuis vaccine, or a
      control group receiving no vaccine). In each cohort, the average daily gain was
      calculated for a selected pen throughout the production stage. Pen (pooled) fecal
      samples were collected bi-weekly and cultured. The odds of Salmonella shedding in
      both vaccinated groups was higher than in the control group (P < 0.05). The
      prevalence of Salmonella shedding declined overall as pigs aged (P = 0.04).
      However, the control pigs showed the smallest decrease in Salmonella shedding
      over the entire production stage, while prevalence of Salmonella shedding in the
      vaccinated groups decreased twice as much as the control group over the entire
      production stage. Salmonella Typhimurium var. Copenhagen DT104, S. Cerro, and S.
      Agona, which had been isolated on the study farm previously, were recovered from
      pigs in this study. Shedding of S. Typhimurium var. Copenhagen decreased over
      time in both vaccine treatment groups. On the other hand, S. Cerro shedding rate
      was lower in the control pigs compared with vaccinated pigs and S. Agona could be
      recovered only from the samples collected from S. Choleraesuis vaccinated pigs.
      The pigs from pens with a higher Salmonella recovery rate experienced slower
      growth compared with pigs from pens where Salmonella was not isolated. This
      latter finding indicates that there might be an economic incentive for producers
      to try to control endemic salmonellosis if effective programs could be developed.

PMID- 21197226
TI  - Assessment of 2 Salmonella enterica serovar Typhimurium-based vaccines against
      necrotic enteritis in reducing colonization of chickens by Salmonella serovars of
      different serogroups.
AB  - This study assessed the protective efficacy of oral vaccination with 2
      experimental attenuated Salmonella Typhimurium-vectored vaccines for necrotic
      enteritis in protecting chickens against intestinal colonization by common
      serovars of Salmonella belonging to the 4 major serogroups affecting chickens.
      Birds were vaccinated orally with 1 * 108 colony-forming units (CFU) of 1 of the
      vaccine strains chi9241 and chi9352, which express a plasmid-encoded partial
      recombinant hypothetical protein gene (tHP) of Clostridium perfringens, at days 1
      and 7 of age, and then were challenged at 14 d of age with 106 CFU of Salmonella
      serovars Anatum, Enteritidis, Heidelberg, Kentucky, or Typhimurium
      (representative serovars of serogroups B, C, D, and E). Birds were necropsied at
      4 wk of age, and samples were collected to determine reduction in tissue and
      intestinal colonization. The chickens vaccinated with chi9241-tHP showed reduced
      colonization by Salmonella Enteritidis (serogroup D) and by Salmonella Heidelberg
      and Salmonella Typhimurium (serogroup B) compared with the control birds. No
      reduction in colonization was observed in the chickens vaccinated with chi9352
      tHP. There was an association between the efficacy of these vaccine strains in
      protecting against necrotic enteritis, assessed on an earlier occasion, and their
      efficacy in protecting against Salmonella colonization. Thus, the choice of an
      attenuated Salmonella Typhimurium vaccine vector for delivery of heterologous
      antigens to chickens should be based partly on the vaccine's value in protecting
      against colonization by serovars within serogroups B and D. Such vectors would
      have the additional benefit of reducing colonization of important Salmonella
      serovars.

PMID- 21197228
TI  - Validation of 2 commercially available enzyme-linked immunosorbent assays for
      adiponectin determination in canine serum samples.
AB  - The aim of this study was to validate 2 commercially available enzyme-linked
      immunosorbent assays (ELISAs) for adiponectin in dogs, 1 canine-specific and 1
      originally designed for measurements in humans. Intra-assay and interassay
      precision was evaluated by multiple measurements in canine serum samples, and
      assay accuracy was indirectly determined by linearity under dilution.
      Interference caused by hemolysis and lipemia was also studied. Both assays were
      subsequently used for measuring adiponectin concentrations in clinically healthy
      dogs and those with different grades of obesity. The intra-assay and inter-assay
      precision was less than 7.5% and 13.5% in serum samples with low and high
      adiponectin concentrations, respectively. Lipemia and hemolysis did not affect
      the results of any of the assays. Both assays were able to differentiate lean
      dogs from those that were overweight or obese on the basis of the measured
      adiponectin concentrations. From these results it can be concluded that canine
      adiponectin concentrations can be measured reliably by means of the 2 ELISAs
      evaluated in this study.

PMID- 21197227
TI  - Surveillance of equine respiratory viruses in Ontario.
AB  - The objective of this project was to develop and implement an active surveillance
      program for the early and rapid detection of equine influenza viruses in Ontario.
      For this purpose, from October 2003 to October 2005, nasopharyngeal swabs and
      acute and convalescent serum samples were collected from 115 client-owned horses
      in 23 outbreaks of respiratory disease in Ontario. Sera were paired and tested
      for antibody to equine influenza 1 (AE1-H7N7), equine influenza 2 (AE2-H3N8),
      equine herpesvirus 1 and 4 (EHV1 and EHV4), and equine rhinitis A and B (ERAV and
      ERBV). Overall, the cause-specific morbidity rate of equine influenza virus in
      the respiratory outbreaks was 56.5% as determined by the single radial hemolysis
      (SRH) test. The AE2-H3N8 was isolated from 15 horses in 5 outbreaks. A 4-fold
      increase in antibody levels or the presence of a high titer against ERAV or ERBV
      was observed in 10 out of 13 outbreaks in which AE2-H3N8 was diagnosed as the
      primary cause of disease. In conclusion, AE2-H3N8 was found to be an important
      contributor to equine respiratory viral disease. Equine rhinitis A and B (ERAV
      and ERBV) represented an important component in the equine respiratory disease of
      performing horses.

PMID- 21197229
TI  - Effects of medetomidine-midazolam-fentanyl IV bolus injections and its reversal
      by specific antagonists on cardiovascular function in rabbits.
AB  - The objective of this study was to investigate the short-term cardiovascular
      effects of intravenous (IV) medetomidine-midazolam-fentanyl (MMF) injections in
      the rabbit using vascular ultrasonography and echocardiography.Anesthesia with
      MMF was induced intramuscularly (IM) in 8 female New Zealand White rabbits before
      3 defined bolus injections of MMF were given IV. Before and for 10 min after each
      MMF injection the following vascular variables [at the left common carotid artery
      (ACC) after the first injection and at the abdominal aorta (AA) after the second
      injection]: vessel diameter (D), peak systolic, minimum diastolic, end-diastolic
      and average blood flow velocities (psBFV, mdBFV, edBFV, Vave), average volumetric
      flow (VFave), resistance index (RI) and pulsatility index (PI) and other clinical
      variables: mean arterial pressure (MAP), heart rate (HR), peripheral arterial
      oxygen saturation and end-tidal CO2 were recorded. Echocardiography was used
      after the third injection to investigate changes in cardiac parameters.
      Additionally, hemodynamic effects were observed at the ACC after complete
      subcutaneous antagonism of anesthesia by atipamezole-flumazenil-naloxone (AFN)
      until recovery of the animals.Medetomidine-midazolam-fentanyl IV caused a
      significant decrease of blood flow velocity in both investigated vessels which
      was associated with a significant decrease of HR and cardiac performance
      indicated by the decrease of FS and average volumetric blood flow. Mean arterial
      pressure significantly increased after each MMF injection; whereas, it
      significantly decreased after AFN injection. Therefore, MMF and AFN should be
      carefully used in rabbits and may not be suitable in patients with ventricular
      dysfunction.

PMID- 21197230
TI  - A transducer for measuring force on surgical sutures.
AB  - The objective of this study was to validate, both in vitro and in an ex vivo
      model, a technique for the measurement of forces exerted on surgical sutures. For
      this purpose, a stainless steel E-type buckle force transducer was designed and
      constructed. A strain gauge was mounted on the central beam of the transducer to
      measure transducer deformation. The transducer was tested and calibrated on a
      single strand of surgical suture during cyclic loading. Further validation was
      performed using a previously published cadaveric model of laryngoplasty in the
      horse. Linear regression of transducer output with actual force during
      calibration tests resulted in mean R2 values of 1.00, 0.99, and 0.99 for rising
      slope, falling slope, and overall slope, respectively. The R2 was not less than
      0.96 across an average of 75 cycles per test. The difference between rising slope
      and falling slope was 4%. Over 45 846 samples, the predicted force from
      transducer output showed a mean error of 4%. In vitro validation produced an
      adjusted R2 of 0.99 when the force on the suture was regressed against
      translaryngeal pressure in a mixed-effects model. E-type buckle force transducers
      showed a highly linear output over a physiological force range when applied to
      surgical suture in vitro and in an ex vivo model of laryngoplasty. With
      appropriate calibration and short-term in vivo implantation, these transducers
      may advance our knowledge of the mechanisms of success and failure of techniques,
      such as laryngoplasty, that use structural suture implants.

PMID- 21197231
TI  - Sensory nerve conduction and nociception in the equine lower forelimb during
      perineural bupivacaine infusion along the palmar nerves.
AB  - The purpose of this investigation was to study lateral palmar nerve (LPN) and
      medial palmar nerve (MPN) morphology and determine nociception and sensory nerve
      conduction velocity (SNCV) following placement of continuous peripheral nerve
      block (CPNB) catheters along LPN and MPN with subsequent bupivacaine (BUP)
      infusion. Myelinated nerve fiber distribution in LPN and MPN was examined after
      harvesting nerve specimens in 3 anesthetized horses and processing them for
      morphometric analysis. In 5 sedated horses, CPNB catheters were placed along each
      PN in both forelimbs. Horses then received in one forelimb 3 mL 0.125% BUP
      containing epinephrine 1:200 000 and 0.04% NaHCO(3) per catheter site followed by
      2 mL/h infusion over a 6-day period, while in the other forelimb equal amounts of
      saline (SAL) solution were administered. The hoof withdrawal response (HWR)
      threshold during pressure loading of the area above the dorsal coronary band was
      determined daily in both forelimbs. On day 6 SNCV was measured under general
      anesthesia of horses in each limb's LPN and MPN to detect nerve injury, followed
      by CPNB catheter removal. The SNCV was also recorded in 2 anesthetized non
      instrumented horses (sham controls). In both LPN and MPN myelinated fiber
      distributions were bimodal. The fraction of large fibers (>7 MUm) was greater in
      the MPN than LPN (P < 0.05). Presence of CPNB catheters and SAL administration
      did neither affect measured HWR thresholds nor SNCVs, whereas BUP infusion
      suppressed HWRs. In conclusion, CPNB with 0.125% BUP provides pronounced
      analgesia by inhibiting sensory nerve conduction in the distal equine forelimb.

PMID- 21197232
TI  - Distribution of capsular serotypes and virulence markers of Streptococcus suis
      isolated from pigs with polyserositis in Korea.
AB  - The objective of this study was to determine the capsular serotypes and potential
      virulence factors of Streptococcus suis isolated from pigs with polyserositis.
      Among the 24 isolates evaluated, serotype 3 [7 (29%) of the isolates] and
      serotype 4 [5 (21%)] were the most common. The isolates were also studied for the
      presence of the genes mrp, epf, and sly, which encode muramidase-released protein
      (MRP), extracellular factor (EF), and suilysin (SLY), respectively. Of the 24
      isolates, 8 carried mrp: 4 of serotype 3, 2 of serotype 2, and 2 of serotype 4.
      One mrp(+) isolate (serotype 2) also carried the epf gene. All 24 isolates
      carried the sly gene. The serotype and genotype distribution greatly differed
      from that reported for isolates from pigs with other clinical manifestations of
      S. suis infection in other countries.

PMID- 21197234
TI  - Single-incision laparoscopic surgery: An overview.

PMID- 21197233
TI  - Changes of very low-density lipoprotein concentration in hepatic blood from cows
      with fasting-induced hepatic lipidosis.
AB  - The purpose of this study was to evaluate changes of very low-density lipoprotein
      (VLDL) components in hepatic blood (HB) from 5 nonlactating nonpregnant cows
      fasted from days 0 to 3 and subsequently refed to day 10 and, in addition, to
      assess those of other lipoproteins. Increased phospholipid concentrations in each
      lipoprotein after the start of fasting suggested their availability for the
      surface lipids of lipoproteins. Although the VLDL-triglyceride (TG) concentration
      in HB from all cows increased on day 1, the value on day 4 became similar to that
      on day 0. However, the concentration on day 10 was significantly increased. In
      all cows, the decreased ratio of the VLDL-TG concentration in HB to the non
      esterified fatty acids (NEFA) concentration in portal blood (PB) on day 4
      appeared to reflect relatively decreased secretion of TG as VLDL by NEFA
      excessively mobilized to the liver via PB. The markedly increased ratio on day 10
      was considered to contribute to the improvement of hepatic lipidosis.

PMID- 21197235
TI  - Single-incision laparoscopic surgery.

PMID- 21197237
TI  - Single-incision laparoscopic cholecystectomy: How I do it?
AB  - Single-incision laparoscopic cholecystectomy (SILC) is a relatively new technique
      that is being increasingly used by surgeons around the world. Unlike the multi
      port cholecystectomy, a standardised technique and detailed description of the
      operative steps of SILC is lacking in the literature. This article provides a
      stepwise account of the technique of SILC aimed at surgeons wishing to learn the
      procedure. A brief review of the current literature on SILC follows.

PMID- 21197236
TI  - Single-incision laparoscopic surgery - current status and controversies.
AB  - Scarless surgery is the Holy Grail of surgery and the very raison d'etre of
      Minimal Access Surgery was the reduction of scars and thereby pain and suffering
      of the patients. The work of Muhe and Mouret in the late 80s, paved the way for
      mainstream laparoscopic procedures and it rapidly became the method of choice for
      many intra-abdominal procedures. Single-incision laparoscopic surgery is a very
      exciting new modality in the field of minimal access surgery which works for
      further reducing the scars of standard laparoscopy and towards scarless surgery.
      Natural orifice translumenal endoscopic surgery (NOTES) was developed for
      scarless surgery, but did not gain popularity due to a variety of reasons. NOTES
      stands for natural orifice translumenal endoscopic surgery, a term coined by a
      consortium in 2005. NOTES remains a research technique with only a few clinical
      cases having been reported. The lack of success of NOTES seems to have spurred on
      the interest in single-incision laparoscopy as an eminently doable technique in
      the present with minimum visible scarring, rendering a 'scarless' effect. Laparo
      endoscopic single-site surgery (LESS) is, a term coined by a multidisciplinary
      consortium in 2008 for single-incision laparoscopic surgery. These are
      complementary technologies with similar difficulties of access, lack of
      triangulation and inadequate instrumentation as of date. LESS seems to offer an
      advantage to surgeons with its familiar field of view and instruments similar to
      those used in conventional laparoscopy. LESS remains a evolving special technique
      used successfully in many a centre, but with a significant way to go before it
      becomes mainstream. It currently stands between standard laparoscopy and NOTES in
      the armamentarium of minimal access surgery. This article outlines the
      development of LESS giving an overview of all the techniques and devices
      available and likely to be available in the future.

PMID- 21197238
TI  - Postoperative pain after cholecystectomy: Conventional laparoscopy versus single
      incision laparoscopic surgery.
AB  - BACKGROUND: This study was undertaken to compare the postoperative pain after
      cholecystectomy done by single-incision laparoscopic surgery (SILS) versus
      conventional four-port laparoscopy [conventional laparoscopic surgery (CLS)].
      SILS is a feasible and a promising method for cholecystectomy. It is possible to
      do this procedure without the use of special equipments. While there are cosmetic
      advantages to SILS, it is not clear whether or not the pain is also reduced.
      METHODS: Patients undergoing cholecystectomy for symptomatic gallstones were
      offered the choice of the two methods and the first 100 consecutive patients from
      each group were included in this observational study. Only conventional
      instruments were used to keep the cost of surgery comparable. Pain scores were
      checked 8 hours after the surgery using visual analogue score. Student's t test
      was done to check the statistical significance. RESULTS: We observed no
      significant difference in the pain score between the CLS and SILS (2.78 versus
      2.62). The operative time (OT) was significantly lower in the CLS group (28
      versus 67 minutes). Comparing the OTs of the first 50 patients undergoing SILS
      with the second 50 patients showed a significantly lower OT (79 versus 54
      minutes). We also compared the pain score between these three groups. The second
      half of SILS group had a significantly lower pain score compared to the first
      half (2.58 versus 2.84). This group also had a lower pain score compared to
      conventional laparoscopy group but the difference was not statistically
      significant (2.58 versus 2.78). CONCLUSION: Although there was no significant
      difference in the overall postoperative pain as OT decreases with surgeon's
      experience in single-incision laparoscopic cholecystectomy, postoperative pain at
      8 hours appears to favour this method over conventional laparoscopic
      cholecystectomy.

PMID- 21197239
TI  - Single-incision multi-port laparoscopic appendectomy: How I do it.
AB  - INTRODUCTION: Single-incision laparoscopic surgery (SILS) appendectomy seeks to
      further minimise the trauma of parietal access of laparoscopic appendectomy.
      METHODS: We present our initial experience of 17 cases of SILS appendectomy which
      were completed using conventional laparoscopic instruments. We utiliesd a single
      incision multi-port laparoscopic appendectomy (SIMPLA) technique. RESULTS: The
      operative time was 63 +/- 20 min, blood loss 6.5 +/- 5 mL, bowel movement
      (passing stool) occurred in 2.6 +/- 0.6 days. Most patients were discharged on
      the first operative day on oral diet. The analgesic usage and pain scores were
      similar to multi-port laparoscopic appendectomy. No complications were noted at
      follow-up till 4 weeks and the surgical wound healed in all patients with an
      inconspicuous scar. CONCLUSION: Our initial experience with SILS appendectomy
      demonstrates its feasibility and supports the promise of minimising further the
      access of laparoscopic surgery. The clear advantage is its cosmetic benefit.

PMID- 21197240
TI  - Single-incision trans-abdominal preperitoneal mesh hernioplasty.
AB  - Single-incision laparoscopy is being used to carry out a wide variety of
      laparoscopic operations since its introduction in 2007. Various case reports and
      studies have demonstrated the safety and feasibility of single-incision
      laparoscopic transabdominal preperitoneal (TAPP) and totally extra-peritoneal
      mesh hernioplasty. However, till date, its apparent advantages have been mainly
      cosmetic and related to patient satisfaction. We have been performing single
      incision laparoscopic TAPP mesh hernioplasty since June 2009 using conventional
      laparoscopic instruments. Here, we describe our technique that is aimed at
      standardising the method.

PMID- 21197241
TI  - Single-incision laparoscopic intraperitoneal onlay mesh hernioplasty for anterior
      abdominal wall hernia: A safe and feasible approach.
AB  - BACKGROUND: Single-incision laparoscopic surgery is being increasingly performed
      in experienced laparoscopic centres. The primary aim is at improving the cosmetic
      outcome of surgery without compromising the safety of the operation. The
      challenge of this surgery lies in limited range of movement of the instruments
      due to proximity of working ports and limited triangulation. METHODS: We describe
      our first four consecutive cases of single-incision laparoscopic intraperitoneal
      onlay mesh hernioplasty for anterior abdominal wall hernia repair during a period
      of June to July 2009. Operative time, hospital stay and postoperative pain were
      assessed, and follow up was done for 3 months. RESULTS: Three patients were
      discharged on first postoperative day and one on second postoperative day without
      any complications. CONCLUSIONS: Based on our experience, we believe that the
      procedure is feasible without additional risk. Cosmetic benefit is clear;
      however, beyond that the actual outcome with respect to patient recovery,
      postoperative pain and long-term complications needs to be evaluated and compared
      to standard laparoscopic intraperitoneal onlay mesh hernioplasty.

PMID- 21197242
TI  - Minimally invasive single-site surgery for the digestive system: A technological
      review.
AB  - Minimally Invasive Single Site (MISS) surgery is a better terminology to explain
      the novel concept of scarless surgery, which is increasingly making its way into
      clinical practice. But, there are some difficulties. We review the existing
      technologies for MISS surgery with regards to single-port devices, endoscope and
      camera, instruments, retractors and also the future perspectives for the
      evolution of MISS surgery. While we need to move ahead cautiously and wait for
      the development of appropriate technology, we believe that the "Ultimate form of
      Minimally Invasive Surgery" will be a hybrid form of MISS surgery and Natural
      Orifice Transluminal Endoscopic Surgery, complimented by technological
      innovations from the fields of robotics and computer-assisted surgery.

PMID- 21197243
TI  - Minimal invasive single-site surgery in colorectal procedures: Current state of
      the art.
AB  - BACKGROUND: Minimally invasive single-site (MISS) surgery has recently been
      applied to colorectal surgery. We aimed to assess the current state of the art
      and the adequacy of preliminary oncological results. METHODS: We performed a
      systematic review of the literature using Pubmed, Medline, SCOPUS and Web of
      Science databases. Keywords used were "Single Port" or "Single-Incision" or
      "LaparoEndoscopic Single Site" or "SILSTM" and "Colon" or "Colorectal" and
      "Surgery". RESULTS: Twenty-nine articles on colorectal MISS surgery have been
      published from July 2008 to July 2010, presenting data on 149 patients. One study
      reported analgesic requirement. The final incision length ranged from 2.5 to 8
      cm. Only two studies reported fascial incision length. There were two port site
      hernias in a series of 13 patients (15.38%). Two "fully laparoscopic" MISS
      procedures with preparation and achievement of the anastomosis completely
      intracorporeally are reported. Future site of ileostomy was used as the sole
      access for the procedures in three studies. Lymph node harvesting, resection
      margins and length of specimen were sufficient in oncological cases. CONCLUSIONS:
      MISS colorectal surgery is a challenging procedure that seems to be safe and
      feasible, but the existing clinical evidence is limited. In selected cases, and
      especially when an ileostomy is planned, colorectal surgery may be an ideal
      indication for MISS surgery leading to a no-scar surgery. Despite preliminary
      oncological results showing the feasibility of MISS surgery, we want to stress
      the need to standardize the technique and carefully evaluate its application in
      oncosurgery under ethical committee control.

PMID- 21197244
TI  - Single-port splenectomy: Current update and controversies.
AB  - Multiport laparoscopic splenectomy (LS) is considered the "gold standard" for the
      management of surgical diseases in normal or slightly enlarged spleens. The
      concept of minimal-invasive surgical techniques has progressed since the early
      1990s from standard multiport laparoscopy to natural orifice transluminal
      endoscopic surgery (NOTES) and, more recently, to single-port access (SPA). In
      this paper, we describe our technique for SPA splenectomy and provide a critical
      review of the current literature on SPA for splenic diseases.Preliminary results
      published to date indicate that the spleen can be safely removed using single
      incision surgery and all the authors have unanimously endorsed the feasibility of
      this approach. However, available evidence is still scarce. It is based only on
      case reports and one small series, with a total of 17 patents and, therefore,
      firm conclusions cannot yet be drawn and more experience and comparative trials
      are needed to determine the exact role of this interesting new approach.

PMID- 21197245
TI  - Single-incision laparoscopic splenectomy.
AB  - Single-incision laparoscopic surgery (SILS) is a rapidly evolving field as a
      bridge between traditional laparoscopic surgery and natural orifice transluminal
      endoscopic surgery. We present a case of SILS splenectomy performed with
      conventional laparoscopic instruments in a 7-month-old boy with the diagnosis of
      multiple splenic abscesses. A 3-cm umbilical incision was used for the placement
      of two (5 mm) trocars and one 10-mm videoscope (30 degrees ). Conventional
      laparoscopic dissector and grasper were the main tools during surgical procedure.
      Spleen was removed through the umbilical incision. Although procedures like
      aingle-incision cholecystectomy have been reported, to the best of our knowledge
      this is the first report of SILS splenectomy using conventional laparoscopic
      instruments reported from India and is perhaps the first in an infant in the
      world literature.

PMID- 21197246
TI  - Single-incision laparoscopic splenectomy with innovative gastric traction suture.
AB  - Laparoscopic splenectomy is now the gold standard for patients with idiopathic
      thrombocytopenic purpura (ITP) undergoing splenectomy. There are a few reports in
      literature on single-incision laparoscopic (SIL) splenectomy. Herein, we describe
      a patient undergoing SIL splenectomy for ITP without the use of a disposable port
      device. We report a 20-year-old female patient with steroid-refractory ITP having
      a platelet count of 14,000/cmm who underwent a SIL splenectomy. Dissection was
      facilitated by the use of a single articulating grasper and a gastric traction
      suture and splenic vessels were secured at the hilum with an endo-GIA stapler.
      She made an uneventful postoperative recovery and was discharged on the second
      postoperative day. She is doing well with no visible scar at 8-month follow-up.

PMID- 21197247
TI  - Laparoendoscopic single-site surgery in gynaecology: A new frontier in minimally
      invasive surgery.
AB  - REVIEW OBJECTIVE: To review the recent developments and published literature on
      laparoendoscopic single-site (LESS) surgery in gynaecology. RECENT FINDINGS:
      Minimally invasive surgery has become a standard of care for the treatment of
      many benign and malignant gynaecological conditions. Recent advances in
      conventional laparoscopy and robotic-assisted surgery have favorably impacted the
      entire spectrum of gynaecological surgery. With the goal of improving morbidity
      and cosmesis, continued efforts towards refinement of laparoscopic techniques
      have lead to minimization of size and number of ports required for these
      procedures. LESS surgery is a recently proposed surgical term used to describe
      various techniques that aim at performing laparoscopic surgery through a single,
      small-skin incision concealed within the umbilicus. In the last 5 years, there
      has been a surge in the developments in surgical technology and techniques for
      LESS surgery, which have resulted in a significant increase in utilisation of
      LESS across many surgical subspecialties. Recently published outcomes data
      demonstrate feasibility, safety and reproducibility for LESS in gynaecology. The
      contemporary LESS literature, extent of gynaecological procedures utilising these
      techniques and limitations of current technology will be reviewed in this
      manuscript. CONCLUSIONS: LESS surgery represents the newest frontier in minimally
      invasive surgery. Comparative data and prospective trials are necessary in order
      to determine the clinical impact of LESS in treatment of gynaecological
      conditions.

PMID- 21197248
TI  - Single-incision total laparoscopic hysterectomy.
AB  - Single-incision laparoscopic surgery is an alternative to conventional multiport
      laparoscopy. Single-access laparoscopy using a transumbilical port affords
      maximum cosmetic benefits because the surgical incision is hidden in the
      umbilicus. The advantages of single-access laparoscopic surgery may include less
      bleeding, infection, and hernia formation and better cosmetic outcome and less
      pain. The disadvantages and limitations include longer surgery time, difficulty
      in learning the technique, and the need for specialized instruments. Ongoing
      refinement of the surgical technique and instrumentation is likely to expand its
      role in gynecologic surgery in the future. We perform single-incision total
      laparoscopic hysterectomy using three ports in the single transumbilical
      incision.

PMID- 21197249
TI  - Single-incision laparoscopic myomectomy.
AB  - Laparoscopic myomectomy is a minimally invasive surgical option for the treatment
      of uterine leiomyomas. Single-incision laparoscopy is a relatively new concept
      that has potential in gynaecological surgery although the technical challenges of
      single-incision access have limited the widespread use of the technique. The use
      of intracorporeal suturing is a significant component of the learning curve for
      laparoscopic myomectomy and presents an even greater challenge with single
      incision laparoscopic myomectomy. This article describes a surgeon's approach to
      single-incision laparoscopic myomectomy.

PMID- 21197250
TI  - Single-incision bilateral laparoscopic oophorectomy.
AB  - Although single-incision laparoscopic surgery made an appearance on the surgical
      scene only recently, it is being increasingly applied in the treatment of a
      variety of disorders. We report single-incision bilateral laparoscopic
      oophorectomy and salpingooophorectomy performed in two patients who had
      previously undergone breast conservation surgery for early breast cancer. Each
      procedure was undertaken using two 5-mm and one 3-mm ports inserted through a 2
      cm transverse supraumbilical incision and standard laparoscopic instruments. The
      operative time was 50 and 65 min respectively and the blood loss negligible. The
      patients were discharged 36 and 24 h after surgery, required minimal
      postoperative analgesia and remain well at a follow up of 19 and 17 months,
      respectively. With the benefit of improved cosmesis, the single-incision approach
      holds the potential to replace the traditional bilateral laparoscopic
      oophorectomy.

PMID- 21197251
TI  - Urological applications of single-site laparoscopic surgery.
AB  - Single-port, single-incision laparoscopy is part of the natural development of
      minimally invasive surgery. Refinement and modification of laparoscopic
      instrumentation has resulted in a substantial increase in the use of
      laparoendoscopic single-site surgery (LESS) in urology over the past 2 years.
      Since the initial report of single-port nephrectomy in 2007, the majority of
      laparoscopic procedures in urology have been described with a single-site
      approach. This includes surgery on the adrenal, ureter, bladder, prostate, and
      testis, for both benign and malignant conditions. In this review, we describe the
      current clinical applications and results of LESS in Urological Surgery. To date
      this evidence comes from small case series in centres of excellence, with good
      results. Further well-designed prospective trials are awaited to validate these
      findings.

PMID- 21197252
TI  - Single-port laparoscopy: Considerations in children.
AB  - As the quest to minimize scars from surgery continues, innovative methods of
      surgery, including single-port surgery, have come to the forefront. Here, we
      review considerations for surgery in children with particular attention to
      appendectomy and cholecystectomy. We discuss the future technologies that will
      aid in single-port surgery and how they apply to the paediatric population.

PMID- 21197253
TI  - Single-incision laparoscopic bariatric surgery.
AB  - BACKGROUND: Bariatric surgery has been established as the best option of
      treatment for morbid obesity. In recent years single-incision laparoscopic
      surgery (SILS) has emerged as another modality of carrying out the bariatric
      procedures. While SILS represents an advance, its application in morbid obesity
      at present is limited. In this article, we review the technique and results of
      SILS in bariatric surgery. METHODS: The PubMed database was searched and totally
      11 series reporting SILS in bariatric surgery were identified and analyzed. The
      case reports were excluded. Since 2008, 114 morbidly obese patients receiving
      SILS bariatric surgeries were reported. RESULTS: The procedures performed
      included SILS gastric banding, sleeve gastrectomy and gastric bypass. No
      mortality was reported in the literatures. Sixteen patients (14.05%) needed an
      additional incision for a liver retractor, a trocar or for conversion. Only one
      complication of wound infection was reported in these series. All the surgeons
      reported that the patients were highly satisfied with the scar. CONCLUSION:
      Because of abundant visceral and subcutaneous fat and multiple comorbidities in
      morbid obesity, it is more challenging for surgeons to perform the procedures
      with SILS. It is clear that extensive development of new instruments and
      technical aspects of these procedures as well as randomized studies to compare
      them with traditional laparoscopy are essential before these procedures can be
      utilized in day-to-day clinical practice.

PMID- 21197254
TI  - Ex-vivo training model for laparoendoscopic single-site surgery.
AB  - BACKGROUND: Laparoendoscopic single-site surgery (LESS) has recently been applied
      successfully in the performance of a host of surgical procedures. Preliminary
      consensus from the experts is that this mode of surgery is technically
      challenging and requires expertise. The transition from trainee to practicing
      surgeon, especially in complex procedures with challenging learning curves, takes
      time and mentor-guided nurturing. However, the trainee needs to use platforms of
      training to gain the skills that are deemed necessary for undertaking the live
      human case. OBJECTIVE: This article aims to demonstrate a step-by-step means of
      how to acquire the necessary instrumentation and build a training model for
      practicing steeplechase exercises in LESS for urological surgeons and trainees.
      The tool built as a result of this could set the platform for performance of
      basic and advanced skills uptake using conventional, bent and articulated
      instruments. A preliminary construct validity of the platform was conducted.
      MATERIALS AND METHODS: A box model was fitted with an R-Port(TM) and camera.
      Articulated and conventional instruments were used to demonstrate basic exercises
      (e.g. glove pattern cutting, loop stacking and suturing) and advanced exercises
      (e.g. pyeloplasty). The validation included medical students (M), final year
      laparoscopic fellows (F) and experienced consultant laparoscopic surgeons (C)
      with at least 50 LESS cases experience in total, were tested on eight basic skill
      tasks (S) including manipulation of the flexible cystoscope (S1), hand eye
      coordination (S2), cutting with flexible scissors (S3), grasping with flexible
      needle holders (S4), two-handed maneuvers (S5), object translocation (S6), cross
      hand suturing with flexible instruments (S7) and conduction of an ex-vivo
      pyeloplasty. RESULTS: The successful application of the box model was
      demonstrated by trainee based exercises. The cost of the kit with circulated
      materials was less than L150 (Pounds Sterling). The noncamera handling skills (S2
      S8) of the ex-vivo training model for LESS can distinguish between
      laparoscopically naive fellows and experienced consultants in LESS. S4-S8 showed
      the highest level of construct validity, by accurately differentiating among the
      M, F and C groups. CONCLUSION: LESS requires a significant amount of skill and
      has an inherent steep learning curve. The ex-vivo model described provides a cost
      effective means that a trainee or training unit can build for optimising
      preliminary skill acquisition in LESS for urological trainees. It has construct
      validity in several tasks. Such platform models should be tested further with an
      emphasis on rapid sequence uptake of optimal skills, prior to undertaking the
      live human case.

PMID- 21197255
TI  - Our ideas for introduction of single-port surgery.
AB  - Single-port surgery, which is also called single-incision laparoscopic surgery
      (SILS), laparoscopic single-site surgery, or single-port access surgery, has been
      performed in several countries. However, it has not been widely adopted
      throughout the world because there still remain some challenging problems to be
      solved, in terms of safety and technology, and the majority of devices specific
      to SILS are under development and have not been approved by the Japanese
      Pharmaceutical Affairs Law. Herein, we introduce single-incision access using
      existing surgical devices that will give us the opportunity to adopt SILS to our
      hospital.

PMID- 21197256
TI  - One-handed knot tying technique in single-incision laparoscopic surgery.
AB  - In an open surgery, two-handed as well as one-handed knot tying is commonplace.
      Knot tying in laparoscopic surgery traditionally involves the use of two
      instruments (for fashioning an intracorporeal knot) or passing of a ligature
      around a tubular structure, exteriorising it, fashioning a knot, and sliding it
      down with a knot-pusher (external slip knot). With increasing interest in
      expanding applications of single-incision laparoscopic surgery (SILS), surgeons
      are faced with new challenges. In SILS it is not usually possible to utilise two
      instruments for knot tying as they lie almost parallel. We describe a novel one
      handed knot tying technique devised specifically for use in SILS.

PMID- 21197257
TI  - Use of operative laparoscopes in single-port surgery: The forgotten tool.
AB  - Single-port surgery is an emerging advancement in the field of minimally invasive
      surgery. Several different techniques and tools have been developed to decrease
      the invasiveness of various operations. Amongst these new developments, many
      general surgeons have overlooked an important tool, the operative laparoscope.
      These telescopes reduce the number of ports placed during minimally invasive
      operations by providing both visualization and operative channels to accommodate
      instruments. We have described several simple techniques that employ the
      operative laparoscope to reduce the number of incisions in laparoscopic surgery
      with good outcomes. Single-port surgery has been shown to be safe and effective
      and may someday replace traditional laparoscopy in the performance of minimally
      invasive operations.

PMID- 21197258
TI  - 6-month results of TransDiscal Biacuplasty on patients with discogenic low back
      pain: preliminary findings.
AB  - STUDY DESIGN: Prospective observational study. OBJECTIVE: Our aim is to
      investigate the efficacy and safety of TransDiscal Biacuplasty. SUMMARY OF
      BACKGROUND DATA: Chronic discogenic pain is one of the leading causes of low back
      pain; however, the condition is not helped by most non-invasive methods. The
      results of major surgical operations for these patients are unsatisfactory.
      Recently, attention has shifted to disk heating methods for treatment.
      TransDiscal Biacuplasty is one of the minimally invasive treatment methods. The
      method was developed as an alternative to spinal surgical practices and
      Intradiscal Electrothermal Therapy for treatment of patients with chronic
      discogenic pain. METHODS: The candidates for this study were patients with
      chronic discogenic pain that did not respond to conservative treatment. The main
      criteria for inclusion were: the existence of axial low back pain present for 6
      months; disc degeneration or internal disc disruption at a minimum of one level,
      and maximum of two levels, in MR imaging; and positive discography. Physical
      function was assessed using the Oswestry Disability Index when measuring the pain
      with VAS. Patient satisfaction was evaluated using a 4-grade scale. Follow-ups
      were made 1, 3, and 6 months after treatment. RESULTS: 15 patients were treated
      at one or two levels. The mean patient age was 43.1 +/- 9.2 years. We found the
      mean symptom duration to be 40.5 +/- 45.7 months. At the sixth month, 57.1% of
      patients reported a 50% or more reduction in pain, while 78.6% of patients
      reported a reduction of at least two points in their VAS values. In the final
      check, 78.6% of patients reported a 10-point improvement in their Oswestry
      Disability scores compared to the initial values. No complications were observed
      in any of the patients. CONCLUSIONS: TransDiscal Biacuplasty is an effective and
      safe method.

PMID- 21197259
TI  - Experimental ablation of the pancreas with high intensity focused ultrasound
      (HIFU) in a porcine model.
AB  - The aim of this study was to determine the feasibility and safety of high
      intensity focused ultrasound's (HIFU) in pancreatic diseases. Twelve pigs were
      divided into three groups. The pancreases of pigs in Group A were ablated
      directly with HIFU, but those in Group B and C ablated by extracorporeal HIFU.
      The pigs in Group C were sacrificed at day 7 after HIFU. Serological parameters
      were determined pre-operation and post-operation. The entire pancreas was removed
      for histological examination. Each animal tolerate the HIFU ablation well. The
      complete necrosis was observed in targeted regions. The margins of the necrotic
      regions were clearly delineated from the surrounding normal tissues. Infiltration
      of inflammatory cells and phorocytosis on the boundary were found in group C.
      Blood and urine amylase levels were relatively steady after HIFU. No acute
      pancreatitis or severe complications occurred. In conclusion, HIFU ablation on
      the pancreas was safe and effective in experimental pigs.

PMID- 21197261
TI  - Complications of methylene blue dye in breast surgery: case reports and review of
      the literature.
AB  - INTRODUCTION: Methylene blue dye has been used worldwide successfully with few
      complications in breast surgery. We present two different complications involving
      methylene blue: 1) skin and parenchymal necrosis when dye was injected in a
      subdermal fashion and 2) Mycoplasma infection caused by contaminated methylene
      blue in breast reduction surgery. METHODS: We present two cases seen at the
      University of Arizona during 2008 and referred to a breast surgeon for
      management. We evaluated and managed complications of methylene blue dye injected
      by 2 referring surgeons for different indications. A review of the literature was
      performed. RESULTS: The first case is a 67 year old female diagnosed with
      infiltrating ductal carcinoma of the left breast for which she was treated by her
      initial surgeon with left segmental mastectomy and sentinel node biopsy. The
      operating surgeon injected methylene blue in a subareolar subdermal fashion
      (distant from the primary tumor); unfortunately the patient suffered skin and
      breast necrosis requiring multiple surgical debridements and finally achieving
      delayed primary closure. The second case is a 45 year old female with
      infiltrating lobular carcinoma with a history of Mycoplasma infection secondary
      to methylene blue injected for breast reduction surgery. She required multiple
      debridements and had granulomas masquerading as cancer on MRI that confounded her
      extent of disease. CONCLUSIONS: The use of methylene blue dye in breast surgery
      is not without risk. In both cases methylene blue was responsible for
      complications requiring surgical debridement for local wound problems. In each
      case severe necrosis and infection were present. Methylene blue may cause not
      only significant morbidity, but may also produce cosmetically unsatisfactory
      results.

PMID- 21197260
TI  - Prognostic factors for failure after prostatectomy.
AB  - Several randomized studies have been completed in prostate cancer that show a
      benefit to immediate postoperative treatment in patients undergoing
      prostatectomy. In one of the studies, there was even a survival advantage. In
      spite of those positive findings, there has been some reluctance to uniformly
      offer adjuvant treatment to patients. The perception is that the risk is not
      really high enough to warrant the risk of toxicity that comes with treatment.
      There are clearly factors that can help predict who is at the highest risk. Our
      purpose is to review those factors and identify patients that have a high enough
      risk justifying immediate treatment.

PMID- 21197263
TI  - Letter to the editor.

PMID- 21197264
TI  - Personalized medicine: part 3: challenges facing health care plans in
      implementing coverage policies for pharmacogenomic and genetic testing.

PMID- 21197262
TI  - Targeted therapies in cancer - challenges and chances offered by newly developed
      techniques for protein analysis in clinical tissues.
AB  - In recent years, new anticancer therapies have accompanied the classical
      approaches of surgery and radio- and chemotherapy. These new forms of treatment
      aim to inhibit specific molecular targets namely altered or deregulated proteins,
      which offer the possibility of individualized therapies.The specificity and
      efficiency of these new approaches, however, bring about a number of challenges.
      First of all, it is essential to specifically identify and quantify protein
      targets in tumor tissues for the reasonable use of such targeted therapies.
      Additionally, it has become even more obvious in recent years that the presence
      of a target protein is not always sufficient to predict the outcome of targeted
      therapies. The deregulation of downstream signaling molecules might also play an
      important role in the success of such therapeutic approaches. For these reasons,
      the analysis of tumor-specific protein expression profiles prior to therapy has
      been suggested as the most effective way to predict possible therapeutic results.
      To further elucidate signaling networks underlying cancer development and to
      identify new targets, it is necessary to implement tools that allow the rapid,
      precise, inexpensive and simultaneous analysis of many network components while
      requiring only a small amount of clinical material.Reverse phase protein
      microarray (RPPA) is a promising technology that meets these requirements while
      enabling the quantitative measurement of proteins. Together with recently
      developed protocols for the extraction of proteins from formalin-fixed, paraffin
      embedded (FFPE) tissues, RPPA may provide the means to quantify therapeutic
      targets and diagnostic markers in the near future and reliably screen for new
      protein targets.With the possibility to quantitatively analyze DNA, RNA and
      protein from a single FFPE tissue sample, the methods are available for
      integrated patient profiling at all levels of gene expression, thus allowing
      optimal patient stratification for individualized therapies.

PMID- 21197265
TI  - Efficacy and safety of a lower-dose valganciclovir (valcyte) regimen for
      cytomegalovirus prophylaxis in kidney and pancreas transplant recipients.
AB  - PURPOSE: We evaluated the efficacy and safety of the current cytomegalovirus
      (CMV) prophylaxis regimen used at Virginia Mason Medical Center in Seattle.
      METHODS: A single-center, retrospective analysis was conducted in a regional
      renal transplantation center at a tertiary teaching facility. STUDY POPULATION:
      Seventy patients who underwent kidney and/or pancreas transplantation from
      October 2006 through December 2008 were observed for a period of six months after
      the procedure. Transplant recipients at risk for developing CMV disease received
      valganciclovir 450 mg daily. RESULTS: Outcome measures were incidence of CMV
      disease and incidence of severe leukopenia during the six-month postoperative
      period. Of 70 patients, seven (10%) developed CMV disease and five (7.1%)
      developed severe leukopenia while taking valganciclovir. Based on donor (D) and
      recipient (R) CMV serostatus, the incidence of CMV disease and severe leukopenia
      incidence was highest in the D+/R- group. Severe leukopenia developed in one
      patient with CMV disease who had a D+/R-kidney transplant. No statistical
      calculations were performed. CONCLUSION: The current lower-dose valganciclovir
      regimen at our institution was found to be efficacious and safe, and it provided
      significant cost savings.

PMID- 21197267
TI  - Pharmaceutical approval update.

PMID- 21197266
TI  - The burden of psoriatic arthritis: a literature review from a global health
      systems perspective.
AB  - OBJECTIVE: We sought to evaluate the clinical, economic, and humanistic burden of
      illness in patients with psoriatic arthritis (PsA). STUDY DESIGN: We performed a
      literature review. METHODS: Our literature search, conducted between 1998 and
      2009, included published studies that (1) considered the direct and indirect
      costs of PsA; reported measures of clinical burden, including mortality, physical
      function, quality of life, and productivity; and (3) reported comorbid conditions
      in patients with PsA. RESULTS: We retrieved and reviewed a total of 49 studies.
      Compared with the general population, patients with PsA had lower health-related
      quality of life and an increased risk of co-morbid conditions, especially
      cardiovascular disease. In the U.S., the direct annual health care costs for PsA
      are estimated to be as high as $1.9 billion. Total indirect costs associated with
      PsA account for 52% to 72% of total costs. Both direct and indirect costs of PsA
      increase with worsening physical function and disease activity. CONCLUSION: PsA
      imposes a considerable economic and quality-of-life burden to patients and
      society. Clinical features of PsA, including comorbid conditions and disease
      activity, contribute to reduced physical and psychosocial health-related quality
      of life. The clinical burden of PsA contributes to direct medical costs
      attributable to the utilization of health care resources. As a result of the
      physical functioning limitations imposed by PsA, indirect costs such as
      disability and lost productivity are substantial drivers of the total costs of
      care.

PMID- 21197268
TI  - American academy of physical medicine and rehabilitation, 71st annual assembly.

PMID- 21197269
TI  - Guillain-barre syndrome animal model: the first proof of molecular mimicry in
      human autoimmune disorder.
AB  - Molecular mimicry between self and microbial components has been proposed as the
      pathogenic mechanism of autoimmune diseases, and this hypothesis is proven in
      Guillain-Barre syndrome. Guillain-Barre syndrome, the most frequent cause of
      acute neuromuscular paralysis, sometimes occurs after Campylobacter jejuni
      enteritis. Gangliosides are predominantly cell-surface glycolipids highly
      expressed in nervous tissue, whilst lipo-oligosaccharides are major components of
      the Gram-negative bacterium C. jejuni outer membrane. IgG autoantibodies to GM1
      ganglioside were found in the sera from patients with Guillain-Barre syndrome.
      Molecular mimicry was demonstrated between GM1 and lipo-oligosaccharide of C.
      jejuni isolated from the patients. Disease models by sensitization of rabbits
      with GM1 and C. jejuni lipo-oligosaccharide were established. Guillain-Barre
      syndrome provided the first verification that an autoimmune disease is triggered
      by molecular mimicry. Its disease models are helpful to further understand the
      molecular pathogenesis as well as to develop new treatments in Guillain-Barre
      syndrome.

PMID- 21197270
TI  - Effect of Host Genetic Variation on the Pharmacokinetics and Clinical Response of
      Non-nucleoside Reverse Transcriptase Inhibitors.
AB  - Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have been used widely
      for treating human immunodeficiency virus type 1 (HIV-1) infected patients as a
      component of highly active antiretroviral therapy (HAART) and for the prevention
      of mother-to-child transmission (MTCT). Cytochrome P450 (CYP) 2B6 is an important
      hepatic isoenzyme responsible for the metabolism of NNRTIs including efavirenz
      and nevirapine. Recent pharmacogenetic studies have shown that CYP2B6 genetic
      variants alter hepatic CYP2B6 protein expression and function, and the
      pharmacokinetics of several CYP2B6 substrates. In particular, the CYP2B6-G516T
      polymorphism in exon 4 affects the pharmacokinetics of efavirenz. Other studies
      have shown associations of the CYP2B6-G516T genotype with nevirapine
      pharmacokinetics and central nervous system adverse effects related to efavirenz
      use. In total, CYP2B6 genetic variants are important determinants of efavirenz
      and nevirapine pharmacokinetics . Further studies are needed to identify the
      associations of CYP2B6 genetic variants with the development of NNRTI resistant
      viruses.

PMID- 21197272
TI  - IgG responses to tissue-associated antigens as biomarkers of immunological
      treatment efficacy.
AB  - We previously demonstrated that IgG responses to a panel of 126 prostate tissue
      associated antigens are common in patients with prostate cancer. In the current
      report we questioned whether changes in IgG responses to this panel might be used
      as a measure of immune response, and potentially antigen spread, following
      prostate cancer-directed immune-active therapies. Sera were obtained from
      prostate cancer patients prior to and three months following treatment with
      androgen deprivation therapy (n = 34), a poxviral vaccine (n = 31), and a DNA
      vaccine (n = 21). Changes in IgG responses to individual antigens were identified
      by phage immunoblot. Patterns of IgG recognition following three months of
      treatment were evaluated using a machine-learned Bayesian Belief Network (ML
      BBN). We found that different antigens were recognized following androgen
      deprivation compared with vaccine therapies. While the number of clinical
      responders was low in the vaccine-treated populations, we demonstrate that ML-BBN
      can be used to develop potentially predictive models.

PMID- 21197273
TI  - Expansion and activation kinetics of immune cells during early phase of GVHD in
      mouse model based on chemotherapy conditioning.
AB  - In the present paper, we have investigated early pathophysiological events in
      graft-versus-host disease (GVHD), a major complication to hematopoietic stem cell
      transplantation (HSCT). BLLB/c female mice conditioned with
      busulfan/cyclophosphamide (Bu-Cy) were transplanted with allogeneic male C57BL/6.
      Control group consisted of syngeneic transplanted Balb/c mice. In allogeneic
      settings, significant expansion and maturation of donor dendritic cells (DCs)
      were observed at day +3, while donor T-cells CD8+ were increased at day +5 (230%)
      compared to syngeneic HSCT. Highest levels of inflammatory cytokines IL-2, IFN
      gamma, and TNF-alfa at day +5 matched T-cell activation. Concomitantly naive T
      cells gain effecr-memory phenotype and migrated from spleen to peripheral
      lymphoid organs. Thus, in the very early phase of GHVD following Bu-Cy
      conditioning donor, DCs play an important role in the activation of donor T
      cells. Subsequently, donor naive T-cells gain effector-memory phenotype and
      initiate GVHD.

PMID- 21197271
TI  - DNA vaccination: using the patient's immune system to overcome cancer.
AB  - Cancer is one of the most challenging diseases of today. Optimization of standard
      treatment protocols consisting of the main columns of chemo- and radiotherapy
      followed or preceded by surgical intervention is often limited by toxic side
      effects and induction of concomitant malignancies and/or development of resistant
      mechanisms. This requires the development of therapeutic strategies which are as
      effective as standard therapies but permit the patients a life without severe
      negative side effects. Along this line, the development of immunotherapy in
      general and the innovative concept of DNA vaccination in particular may provide a
      venue to achieve this goal. Using the patient's own immune system by activation
      of humoral and cellular immune responses to target the cancer cells has shown
      first promising results in clinical trials and may allow reduced toxicity
      standard therapy regimen in the future. The main challenge of this concept is to
      transfer the plethora of convincing preclinical and early clinical results to an
      effective treatment of patients.

PMID- 21197275
TI  - Sarcoidosis: yet another masquerader the cardiologist / electrophysiologist has
      to fight with.

PMID- 21197276
TI  - Atrial fibrillation ablation: a single center comparison between remote magnetic
      navigation, cryoballoon and conventional manual pulmonary vein isolation.
AB  - BACKGROUND: The aim of the study was to compare in our center the effect of
      different ablation techniques on intermediate term freedom from atrial
      fibrillation (AF) or atrial tachycardia (AT) in patients affected by refractory
      AF. METHODS AND RESULTS: We retrospectively selected 94 patients who underwent AF
      ablation in our electrophysiological laboratory from June 2007 to December 2009.
      29 patients underwent manual circumferential pulmonary vein isolation (mCPVI), 35
      underwent remote magnetic navigation assisted CPVI (rmtCPVI) and 30 cryoballoon
      CPVI (cCPVI). Antiarrhythmic drugs were systematically stopped 2 months after the
      procedure (end of the "blanking period"). At a mean follow-up of 12,64 +/- 6,41
      months (range 2-31), the success rate for mCPVI group was 65.5% (19 patients),
      66.7 % (20 patients) for the rmtCPVI group and 65.7 % (23 patients) for the cCPVI
      group (p = 0.625). Procedural and fluoroscopy times were significantly reduced in
      the cCPVI group (both p < 0.001). Univariate Cox regression showed that no
      clinical variables were independently associated with recurrence. CONCLUSIONS: In
      our center's experience cCPVI and rmtCPVI have been demonstrated to be as
      effective as mCPVI. cCPVI seemed to be associated with lower procedural and
      fluoroscopy times.

PMID- 21197274
TI  - Gene carriers and transfection systems used in the recombination of dendritic
      cells for effective cancer immunotherapy.
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells. They play a
      vital role in the initiation of immune response by presenting antigens to T cells
      and followed by induction of T-cell response. Reported research in animal studies
      indicated that vaccine immunity could be a promising alternative therapy for
      cancer patients. However, broad clinical utility has not been achieved yet, owing
      to the low transfection efficiency of DCs. Therefore, it is essential to improve
      the transfection efficiency of DC-based vaccination in immunotherapy. In several
      studies, DCs were genetically engineered by tumor-associated antigens or by
      immune molecules such as costimulatory molecules, cytokines, and chemokines.
      Encouraging results have been achieved in cancer treatment using various animal
      models. This paper describes the recent progress in gene delivery systems
      including viral vectors and nonviral carriers for DC-based genetically engineered
      vaccines. The reverse and three-dimensional transfection systems developed in DCs
      are also discussed.

PMID- 21197277
TI  - Improved Flutter Ablation Outcomes Using a 10mm-tip Ablation Catheter.
AB  - INTRODUCTION: Radiofrequency(RF) ablation has become the first line of therapy
      for atrial flutter(AFL). Advances in catheter and mapping technologies have led
      to better understanding and different approaches for treating this arrhythmia. We
      describe the results of different approaches to ablate this arrhythmia. MATERIALS
      AND METHODS: A cohort of 198 patients with isthmus dependent AFL. The techniques
      used were: 10mm-tip catheter with power set to 100w, 8mm-tip catheter with power
      set to 60W and irrigated tip catheter. RESULTS: 212 procedures, including redos
      were done in 198 consecutive patients. We used irrigated tip catheters in 14
      procedures, 8mm-tip in 55 procedures, and 10mm-tip in 143 procedures.
      Bidirectional block was achieved in 97.6% of cases with all techniques, with no
      difference among them. Procedure time was shorter in the 10mm-tip versus 8mm
      tip(69.6+/-30.6min vs.105+/-43min) or irrigated tip(180+/-90min) (P<0.05).
      Fluoroscopy time was also shorter in the 10mm-tip versus 8mm-tip (24+/-18min vs.
      37+/-23min) or irrigated tip (110+/-25min)(P<0.05). The cumulative incidence of
      failure during follow-up was 1.2%/year in the 10mm, 10.1%year in the 8mm and
      6.9%year in the irrigated tip. The survival free of a new procedure was
      significantly higher among 10mm patients. CONCLUSIONS: In our series we found a
      high rate of acute success with the use of different techniques for AFL ablation.
      Procedure and fluoroscopic times were shorter with the use of 10mm-tip as
      compared with the others techniques. The long-term risk of recurrence was lower
      when we used the 10mm-tip catheter and the survival free of a second procedure
      was higher among patients treated with this catheter.

PMID- 21197278
TI  - The role of cardiac magnetic resonance imaging in the evaluation of
      arrhythmogenic right ventricular dysplasia.

PMID- 21197279
TI  - Malignant paroxysmal supraventricular tachycardia.

PMID- 21197280
TI  - Iatrogenic Twiddler's Syndrome: Case Report and Proposed Experimental Model.

PMID- 21197281
TI  - Tachycardia Initiated by One to Two Response and Terminated by ICD Shocks.

PMID- 21197282
TI  - Noxious counterirritation in patients with advanced osteoarthritis of the knee
      reduces MCC but not SII pain generators: A combined use of MEG and EEG.
AB  - CHRONIC PAIN IS MAINLY A RESULT OF TWO PROCESSES: peripheral and central
      sensitization, which can result in neuroplastic changes. Previous psychophysical
      studies suggested a decrease of the so-called pain-inhibiting-pain effect (DNIC)
      in chronic pain patients. We aimed to study the DNIC effect on the neuronal level
      using magnetoencephalography and electroencephalography in 12 patients suffering
      from advanced unilateral knee osteoarthritis (OA). DNIC was induced in patients
      by provoking the typical OA pain by a slightly hyperextended joint position,
      while they received short electrical pain stimuli. Although the patients did not
      report a reduction of electrical pain perception, the cingulate gyrus showed a
      decrease of activation during provoked OA pain, while activity in the secondary
      somatosensory cortex did not change. Based on much stronger DNIC induction at
      comparable intensities of an acute counterirritant pain in healthy subjects this
      result suggests a deficit of DNIC in OA patients. We suggest that the strength of
      DNIC is subject to neuronal plasticity of descending inhibitory pain systems and
      diminishes during the development of a chronic pain condition.

PMID- 21197283
TI  - Intraperitoneal aerosolization of bupivacaine is a safe and effective method in
      controlling postoperative pain in laparoscopic Roux-en-Y gastric bypass.
AB  - INTRODUCTION: Obesity is a worldwide problem and has grown in severity in the
      last few decades making bariatric surgery and, in particular, laparoscopic
      banding and Roux-en-Y gastric bypass efficacious and cost-effective procedures.
      The laparoscopic approach has been shown to offer significant healthcare
      benefits, of particular interests are reports of decreased postoperative pain
      resulting in a shorter hospital stay and an earlier return to normal activity.
      However, many patients still experience significant pain, including shoulder tip
      pain, that require strong analgesia including opiates during their early recovery
      period. The aims of this study were to establish the safe use of the
      aerosolization technique in bariatric surgery and to investigate the possible
      benefits in reducing postoperative pain. METHODS: In this study, fifty patients
      undergoing laparoscopic gastric bypass were recruited and divided into two
      groups; control (n = 25) and therapeutic (n = 25). The control group received
      intraperitoneal aerosolization of 10 mL of 0.9% normal saline while the
      therapeutic group received 10 mL of 0.5% bupivacaine. All the patients had
      standard preoperative, intraoperative, and postoperative care. Pain scores were
      carried out by the nursing staff in recovery and 6 h, 12 h and 24 h
      postoperatively using a standard 0-10 pain scoring scale. In addition, opiate
      consumption via patient-controlled analgesia (PCA) was recorded. RESULTS:
      Aerosolized bupivacaine reduced postoperative pain in comparison to normal saline
      (p < 0.05). However, PCA usage showed no statistically significant change from
      the control group. CONCLUSION: The aims of this study were achieved and we were
      able to establish the safe use of the aerosolization technique in bariatric
      surgery and its benefits in reducing postoperative pain.

PMID- 21197284
TI  - Yellow flag scores in a compensable New Zealand cohort suffering acute low back
      pain.
AB  - BACKGROUND: Despite its high prevalence, most acute low back pain (ALBP) is
      nonspecific, self-limiting with no definable pathology. Recurrence is prevalent,
      as is resultant chronicity. Psychosocial factors (yellow flags comprising
      depression and anxiety, negative pain beliefs, job dissatisfaction) are
      associated with the development of chronic LBP. METHODS: A national insurer
      (Accident Compensation Corporation, New Zealand [NZ]), in conjunction with a NZ
      primary health organization, piloted a strategy for more effective management of
      patients with ALBP, by following the NZ ALBP Guideline. The guidelines recommend
      the use of a psychosocial screening instrument (Yellow Flags Screening
      Instrument, a derivative of Orebro Musculoskeletal Pain Questionnaire). This
      instrument was recommended for administration on the second visit to a general
      medical practitioner (GP). This paper tests whether published cut-points of
      yellow flag scores to predict LBP claims length and costs were valid in this
      cohort. RESULTS: Data was available for 902 claimants appropriately enrolled into
      the pilot. 25% claimants consulted the GP once only, and thus were not requested
      to provide a yellow flag score. Yellow flag scores were provided by 48% claimants
      who consumed two or more GP services. Approximately 60% LBP presentations
      resolved within five GP visits. Yellow flag scores were significantly and
      positively associated with treatment costs and service use, although the
      association was nonlinear. Claimants with moderate yellow flag scores were
      similarly likely to incur lengthy claims as claimants with at-risk scores.
      DISCUSSION: Capturing data on psychosocial factors for compensable patients with
      ALBP has merit in predicting lengthy claims. The validity of the published yellow
      flag cut-points requires further testing.

PMID- 21197285
TI  - Preemptive versus postoperative lumiracoxib for analgesia in ambulatory
      arthroscopic knee surgery.
AB  - We compared the efficacy and safety of preemptive vs postoperative dosing of
      lumiracoxib 400 mg in patients undergoing minor ambulatory arthroscopic knee
      surgery. Eligible patients were randomized to preemptive lumiracoxib,
      postoperative lumiracoxib, and placebo. The main efficacy parameter was pain
      intensity (PI) (0-100 mm visual analog scale) in the target knee upon movement, 2
      hours after surgery. Other efficacy variables included PI in the target knee at
      rest and upon movement at 1, 3, 4, and 24 hours, time to first rescue medication
      intake. In the lumiracoxib preemptive and postoperative groups, the estimated
      treatment difference compared to placebo for primary endpoint was -4.0 (95% CI: 
      9, -1; p = 0.007) and -3.5 (95% CI: -8.5, 0; p = 0.052), respectively. There was
      no statistical significant difference between two active treatment groups (p =
      0.602). Both preemptive and postoperative lumiracoxib resulted in significantly
      lower PI scores at rest and after movement at all time-points and no
      statistically significant difference was observed between the active treatments.
      Time to rescue medication intake was comparable for both active treatments. The
      proportion of adverse events was similar among all groups. We conclude that the
      efficacy of lumiracoxib 400 mg is not affected by the timing of administration
      (preemptive or postoperative).

PMID- 21197286
TI  - Manipulation of pain catastrophizing: An experimental study of healthy
      participants.
AB  - Pain catastrophizing is associated with the pain experience; however, causation
      has not been established. Studies which specifically manipulate catastrophizing
      are necessary to establish causation. The present study enrolled 100 healthy
      individuals. Participants were randomly assigned to repeat a positive, neutral,
      or one of three catastrophizing statements during a cold pressor task (CPT).
      Outcome measures of pain tolerance and pain intensity were recorded. No change
      was noted in catastrophizing immediately following the CPT (F((1,84)) = 0.10, p =
      0.75, partial eta(2) < 0.01) independent of group assignment (F((4,84)) = 0.78, p
      = 0.54, partial eta(2) = 0.04). Pain tolerance (F((4)) = 0.67, p = 0.62, partial
      eta(2) = 0.03) and pain intensity (F((4)) = 0.73, p = 0.58, partial eta(2) =
      0.03) did not differ by group. This study suggests catastrophizing may be
      difficult to manipulate through experimental pain procedures and repetition of
      specific catastrophizing statements was not sufficient to change levels of
      catastrophizing. Additionally, pain tolerance and pain intensity did not differ
      by group assignment. This study has implications for future studies attempting to
      experimentally manipulate pain catastrophizing.

PMID- 21197287
TI  - A multidisciplinary bone metastases clinic at Toronto Sunnybrook Regional Cancer
      Centre - A review of the experience from 1999 to 2005.
AB  - Our objective in this study was to review the experience of a one-stop
      multidisciplinary bone metastases clinic (BMC) that offers a coordinated
      multidisciplinary approach to the care of cancer patients with bone metastases in
      a tertiary cancer centre. Patients with symptomatic bone metastases were referred
      to BMC and assessed by a team of specialists in various disciplines -
      interventional radiology, orthopedic surgery, palliative medicine, and radiation
      oncology. At initial consultation, patient demographics, reasons for referral,
      and case disposition were recorded. From January 1999 to February 2005, a total
      of 272 patients with bone metastases were referred to the BMC. The median age was
      65 years (range 28-95) and median KPS score at consultation was 60 (range 30-90).
      The majority of patients came from home (74%), while others came from a nursing
      home or the hospital (9%). Almost a third (28%) of patients had 2 or more reasons
      of referral, yielding a total of 354 reasons. The most common reason for referral
      was bone pain (42%), bone metastases (21%), high risk for pathological fracture
      (12%), and pathological fracture (10%). Of the 272 patients who received
      consultation, 40% received palliative radiotherapy, 19% received interventional
      surgery, 7% were referred to other support services such as palliative care,
      physiotherapy, and 7% had further investigation or imaging. A multidisciplinary
      clinic is useful for co-coordinating the management of bone metastatic disease in
      symptomatic patients.

PMID- 21197288
TI  - Quality of life measurement in bone metastases: A literature review.
AB  - Quality of life (QOL) has become an important consideration in the care of
      patients with bone metastases as prevalence, incidence and patient survival are
      on the rise. As a result, more interventional studies now measure patient's QOL
      as a meaningful endpoint. However, well-developed bone metastases specific
      quality of life instruments are lacking. A literature review was conducted to
      better understand the nature of QOL instruments used in bone metastases trials. A
      total of 47 articles evaluating QOL in patients with bone metastases were
      identified. Twenty-five different instruments were used to evaluate QOL with
      study-designed questionnaires and the EORTC QLQ-C30 being most commonly employed.
      Many studies used more than one scale or instrument to measure QOL. This makes it
      difficult to compare QOL in bone metastases patients across studies and come to
      any formal conclusions. Therefore, this review demonstrates the need to develop a
      bone module that can be used across countries in future clinical trials.

PMID- 21197289
TI  - An interdisciplinary and collaborative initiative in palliative care research.
AB  - The scale and complexity of palliative care increasingly demands that researchers
      move beyond their own discipline and explore interdisciplinary collaboration. At
      a Palliative Care Research Retreat held in January 2006 at the Toronto Sunnybrook
      Regional Cancer Centre, researchers from multiple care settings with the center
      and from other Toronto hospitals came together with the vision of becoming
      Canadian leaders in palliative care research. As a result of this retreat, five
      interdisciplinary groups were formed to pursue research in the areas of pain and
      symptom management, access to services, translational research, education, and
      communication. An overview of the retreat and direction of research for each
      group is provided.

PMID- 21197290
TI  - Problems and barriers of pain management in the emergency department: Are we ever
      going to get better?
AB  - Pain is the most common reason people visit emergency rooms. Pain does not
      discriminate on the basis of gender, race or age. The state of pain management in
      the emergency department (ED) is disturbing. ED physicians often do not provide
      adequate analgesia to their patients, do not meet patients' expectations in
      treating their pain, and struggle to change their practice regarding analgesia. A
      review of multiple publications has identified the following causes of poor
      management of painful conditions in the ED: failure to acknowledge pain, failure
      to assess initial pain, failure to have pain management guidelines in ED, failure
      to document pain and to assess treatment adequacy, and failure to meet patient's
      expectations. The barriers that preclude emergency physicians from proper pain
      management include ethnic and racial bias, gender bias, age bias, inadequate
      knowledge and formal training in acute pain management, opiophobia, the ED, and
      the ED culture. ED physicians must realize that pain is a true emergency and
      treat it as such.

PMID- 21197291
TI  - A new transmucosal drug delivery system for patients with breakthrough cancer
      pain: the fentanyl effervescent buccal tablet.
AB  - Breakthrough pain, a transitory severe pain with the background of otherwise
      controlled persistent pain has a prevalence between 52% and 67% in outpatients
      with cancer. Medications for such sudden-onset pain require non-invasive delivery
      of a potent and short-acting opioid for rapid pain relief. Although oral
      transmucosal delivery of fentanyl citrate (OTFC) has been shown to provide better
      pain relief than a typical oral opioid administration such as morphine sulfate
      immediate release (MSIR) in the management of breakthrough pain in patients with
      cancer-related pain, newer delivery systems offer a potential for further
      enhancement of pain relief. The fentanyl effervescent buccal tablet (FBT)
      formulation employs a novel drug delivery system that relies on an effervescence
      reaction to improve buccal fentanyl absorption. Using the effervescence reaction
      results in the production and dissipation of carbon dioxide with a dynamic shift
      in pH as the tablet dissolves. The induced low pH favors dissolution of fentanyl
      citrate in saliva (higher water solubility). The subsequent increase in pH
      thereafter favors the buccal absorption of non-ionized fentanyl across the buccal
      mucosa. Such a pH "pumping" mechanism increases the permeation of fentanyl into
      and through the buccal to the vascular system from where the agent is transported
      to the specific opioid receptor sites in the CNS. Compared with OTFC, data in
      healthy volunteers show that the effervescence reaction employed in FBT increases
      the total amount and the speed of absorption of fentanyl being absorbed. Compared
      with OTFC there is an increase in peak fentanyl blood concentrations, and an
      enhancement of the amount of buccal delivery of fentanyl. Such favorable data are
      underlined by the results of clinical studies where the FBT technology was
      studied in patients with breakthrough pain in chronic malignant pathologies.

PMID- 21197292
TI  - A review and critique of assessment instruments for patients with persistent
      pain.
AB  - BACKGROUND: Early identification of individuals at risk of developing persistent
      pain is important to decrease unnecessary treatment costs and disability. However
      there is scant comprehensive information readily available to assist clinicians
      to choose appropriate assessment instruments with sound psychometric and clinical
      properties. OBJECTIVE: A national insurer commissioned the development of a
      compendium of assessment instruments to identify adults with, or at-risk of
      developing, persistent pain. This paper reports on the instrument identification
      and review process. METHODS: A comprehensive systematic literature review was
      undertaken of assessment instruments for persistent pain of noncancer origin, and
      their developmental literature. Only assessment instruments which were developed
      for patients with pain, or tested on them, were included. A purpose-built 'Ready
      Reckoner' scored psychometric properties and clinical utility. RESULTS: One
      hundred sixteen potentially useful instruments were identified, measuring
      severity, psychological, functional and/or quality of life constructs of
      persistent pain. Forty-five instruments were short-listed, with convincing
      psychometric properties and clinical utility. There were no standard tests for
      psychometric properties, and considerable overlap of instrument purpose, item
      construct, wording, and scoring. CONCLUSION: No one assessment instrument
      captured all the constructs of persistent pain. While the compendium focuses
      clinicians' choices, multiple instruments are required for comprehensive
      assessment of adults with persistent pain.

PMID- 21197294
TI  - Opioid-induced proliferation of vascular endothelial cells.
AB  - Angiogenesis is an important issue in cancer research and opioids are often used
      to treat pain in cancer patients. Therefore it is important to know if the use of
      opioids is associated with an aberrant stimulation of tumor growth triggered by
      the stimulation of angiogenesis in cancer patients. Some studies in the
      literature have suggested the presence of the MU3 opioid receptor, known as the
      receptor for many opioids, on endothelial cells, which are key players in the
      process of angiogenesis. In this study we used endothelial cells known to express
      the MU3 opioid receptor (MOR3), to evaluate the effects of morphine on
      angiogenesis. We first investigated the effect of morphine on the proliferation
      of endothelial cells. We showed that morphine is able to stimulate vascular
      endothelial cell proliferation in vitro. This effect of morphine is mediated by
      the mitogen-activated protein kinase (MAPK) pathway as pre-treatment with PD98059
      inhibited this excessive proliferation. Because previous studies indicated nitric
      oxide (NO) as a downstream messenger we investigated the role of NO in the
      aberrant proliferation of endothelial cells. Our data could not confirm these
      findings using intracellular NO measurements and quantitative fluorescence
      microscopy. The potential use and pitfalls of opioids in cancer patients is
      discussed in light of these negative findings.

PMID- 21197293
TI  - C-fiber-related EEG-oscillations induced by laser radiant heat stimulation of
      capsaicin-treated skin.
AB  - Nociceptive input reaches the brain via two different types of nerve fibers,
      moderately fast A-delta and slowly conducting C-fibers, respectively. To explore
      their distinct roles in normal and inflammatory pain we used laser stimulation of
      normal and capsaicin treated skin at proximal and distal arm sites in combination
      with time frequency transformation of electroencephalography (EEG) data.
      Comparison of phase-locked (evoked) and non-phase-locked (total) EEG to laser
      stimuli revealed three significant pain-related oscillatory responses. First, an
      evoked response in the delta-theta band, mediated by A-fibers, was reduced by
      topical capsaicin treatment. Second, a decrease of total power in the alpha-to
      gamma band reflected both an A- and C-nociceptor-mediated response with only the
      latter being reduced by capsaicin treatment. Finally, an enhancement of total
      power in the upper beta band was mediated exclusively by C-nociceptors and
      appeared strongly augmented by capsaicin treatment. These findings suggest that
      phase-locking of brain activity to stimulus onset is a critical feature of A
      delta nociceptive input, allowing rapid orientation to salient and potentially
      threatening events. In contrast, the subsequent C-nociceptive input exhibits
      clearly less phase coupling to the stimulus. It may primarily signal the tissue
      status allowing more long-term behavioral adaptations during ongoing inflammatory
      events that accompany tissue damage.

PMID- 21197295
TI  - Altered sensitivity to mechanical stimulation during prolonged subcutaneous
      administration of endothelin-1 in rats.
AB  - Cancer pain is often difficult to treat. Growing evidence indicates that chemical
      mediators secreted by the tumor itself play an important role in the development
      of cancer pain. One such mediator, endothelin-1 (ET-1) is secreted by different
      tumor types. Studies have indicated that ET-1 induces spontaneous and evoked
      nociception in rodents and in humans. The focus of all these studies has always
      been on a single administration of ET-1. Such an acute exposure to ET-1 however
      bears little resemblance to the clinical condition in which cancer patients are
      exposed continuously for many months to increased levels of ET-1. To improve the
      knowledge of the pathological role of ET-1 in cancer, we developed an animal
      model of prolonged exposure to ET-1. Rats were exposed to subcutaneous
      administration of ET-1 for seven consecutive days, with a total amount of 67.4
      nmol. On days +2, +3, +5, +7, and +10 sensitivity to von Frey hairs and to pin
      prick stimulation were evaluated. Prolonged administration of ET-1 induced signs
      of mechanical allodynia on several time points. Although the administered doses
      were very small, prolonged administration of ET-1 seems to lead to a state of
      mechanical allodynia.

PMID- 21197296
TI  - Long-term outcomes of anthroposophic therapy for chronic low back pain: A two
      year follow-up analysis.
AB  - BACKGROUND: Anthroposophic treatment for chronic low back pain (LBP) includes
      special artistic and physical therapies and special medications. In a previously
      published prospective cohort study, anthroposophic treatment for chronic LBP was
      associated with improvements of pain, back function, and quality of life at 12
      month follow-up. These improvements were at least comparable to improvements in a
      control group receiving conventional care. We conducted a two-year follow-up
      analysis of the anthroposophic therapy group with a larger sample size. METHODS:
      Seventy-five consecutive adult outpatients in Germany, starting anthroposophic
      treatment for discogenic or non-specific LBP of >=6 weeks' duration participated
      in a prospective cohort study. Main outcomes were Hanover Functional Ability
      Questionnaire (HFAQ; 0-100), LBP Rating Scale Pain Score (LBPRS; 0-100), Symptom
      Score (0-10), and SF-36 after 24 months. RESULTS: Eighty-five percent of patients
      were women. Mean age was 49.0 years. From baseline to 24-month follow-up all
      outcomes improved significantly; average improvements were: HFAQ 11.1 points (95%
      confidence interval [CI]: 5.5-16.6; p < 0.001), LBPRS 8.7 (95% CI: 4.4-13.0; p <
      0.001), Symptom Score 2.0 (95% CI: 1.3-2.8; p < 0.001), SF-36 Physical Component
      Summary 6.0 (95% CI: 2.9-9.1; p < 0.001), and SF-36 Mental Component Summary 4.0
      (95% CI: 1.1-6.8; p = 0.007). CONCLUSION: Patients with chronic LBP receiving
      anthroposophic treatment had sustained improvements of symptoms, back function,
      and quality of life, suggesting that larger multicenter rigorous studies may be
      worthwhile.

PMID- 21197298
TI  - Duloxetine for the management of fibromyalgia syndrome.
AB  - Fibromyalgia syndrome (FMS) is a widespread pain condition associated with a wide
      range of additional symptoms including fatigue, insomnia, depression, anxiety and
      stiffness. Duloxetine is one of three medications currently FDA approved for use
      in FMS management. Duloxetine is a mixed serotonin and norepinephrine reuptake
      inhibitor (SNRI) that functions by increasing central nervous system levels of
      serotonin and norepinephrine. This review is a primer on use of duloxetine in FMS
      management and includes information on pharmacology and pharmacokinetics, a
      review of the three duloxetine FMS treatment trials currently in publication, a
      discussion of the safety and tolerability of duloxetine, and patient-focused
      perspectives on duloxetine use in FMS management. Duloxetine has proven efficacy
      in managing pain and mood symptoms in adult FMS patients with and without major
      depressive disorder. However, due to side effects, duloxetine must be used with
      caution in patients with fatigue, insomnia, gastrointestinal complaints,
      headache, cardiovascular disease, bleeding-risk, and in those 24 years of age and
      younger due to risk of suicidality. Duloxetine use should be avoided in patients
      with liver disease or alcoholics. As with all medications, duloxetine is best
      used as part of an individualized regimen that includes nonpharmacologic
      modalities of exercise, education and behavioral therapies.

PMID- 21197297
TI  - Managing joint pain in osteoarthritis: safety and efficacy of hylan G-F 20.
AB  - The use of intra-articular viscosupplementation in the nonoperative management of
      patients with osteoarthritis has become quite popular. Recent clinical data have
      demonstrated that the anti-inflammatory and chondroprotective actions of
      hyaluronic acid viscosupplementation reduce pain while improving patient
      function. We review the basic science and development of viscosupplementation and
      discuss the mounting evidence in support of the efficacy and safety profile of
      hylan G-F 20. Recent evidence suggesting a disease-modifying effect of hylan G-F
      20 is also assessed. Furthermore, although the primary focus of this article is
      on treatment of osteoarthritis of the knee, we also discuss the use of
      viscosupplementation in other joints, such as the hip, ankle, and shoulder.

PMID- 21197299
TI  - Effects of coping statements on experimental pain in chronic pain patients.
AB  - The present study measured the effects of catastrophizing self-statements and
      positive coping self-statements on cold pressor-induced pain. Participants were
      58 adult chronic pain patients with current facial pain. It was hypothesized that
      catastrophizing would lead to a decrease in pain endurance whereas positive
      coping would lead to an increase in pain endurance. It was also hypothesized that
      catastrophizing would lead to an increase in peak pain intensity whereas positive
      coping would lead to a decrease in peak pain intensity. At pretest, participants
      submerged their nondominant hand in the cold pressor. Pain sensitivity ranges
      (PSR) were subsequently determined by calculating the difference between
      tolerance and threshold times. Ratings of peak pain intensity were measured using
      a pressure sensitive bladder/transducer. Participants underwent random assignment
      to either a catastrophizing group or a positive coping self-statement group.
      ANCOVA results revealed that on average, participants employing catastrophizing
      statements as a coping strategy experienced significantly lower PSR (M = 35.53,
      SD = 39.71) compared to participants employing positive coping self-statements (M
      = 73.70, SD = 86.14) when controlling for pretest PSR. Group assignment had no
      significant influence on peak pain intensity ratings. Thus, our results reveal
      that manipulation of coping causes changes in pain endurance.

PMID- 21197300
TI  - Transdermal buprenorphine - a critical appraisal of its role in pain management.
AB  - This paper reviews the current clinical data for the role of transdermal
      buprenorphine (BUP TDS) in the treatment of diverse acute and chronic pain
      syndromes. Literature searches were carried out using PubMed (1988 to June 2009).
      The published findings seem to support hypotheses regarding the rather unique
      analgesic mechanisms of buprenorphine as compared with pure MU-opioids like
      morphine and fentanyl. However, the exact mechanism of this analgesic efficacy
      still remains largely unknown despite recent advances in preclinical
      pharmacological studies. Such assessments have demonstrated the sustained
      antihyperalgesic effect of buprenorphine in diverse animal pain models. These
      findings are supported in a growing number of clinical studies of oral,
      intrathecal, intravenous, and Bup TDS. This review paper focuses almost entirely
      on the clinical experience concerning the transdermal administration of
      buprenorphine, although preclinical aspects are also addressed in order to
      provide a complete picture of the unique pharmacological properties of this
      analgesic drug. Mounting evidence indicates the appropriateness of Bup TDS in the
      treatment of diverse acute and chronic pain syndromes which have been less or not
      responsive to other opioids. Additionally, BUP TDS seems to hold great promise
      for other difficult-to-treat (pain) conditions, such as patients in the intensive
      care setting. However, its use is somewhat tempered by the occurrence of local
      skin reactions which have been shown to be often therapy resistant. Further
      studies are certainly warranted to identify even more precisely the clinical
      syndromes that are most sensitive to buprenorphine treatment, and to compare
      buprenorphine to other opioids in head-to-head trials of acute and chronic pain
      conditions.

PMID- 21197302
TI  - Patient perception of pain care in hospitals in the United States.
AB  - STUDY OBJECTIVE: Assessment of patients' perception of pain control in hospitals
      in the United States. BACKGROUND: Limited data are available regarding the
      quality of pain care in the hospitalized patient. This is particularly valid for
      data that allow for comparison of pain outcomes from one hospital to another.
      Such data are critical for numerous reasons, including allowing patients and
      policy-makers to make data-driven decisions, and to guide hospitals in their
      efforts to improve pain care. The Hospital Quality Alliance was recently created
      by federal policy makers and private organizations in conjunction with the
      Centers for Medicare and Medicare Services to conduct patient surveys to evaluate
      their experience including pain control during their hospitalization. METHODS: In
      March 2008, the results of the Hospital Consumer Assessment of Healthcare
      Providers and Systems (HCAHPS) survey was released for review for health care
      providers and researchers. This survey includes a battery of questions for
      patients upon discharge from the hospital including pain-related questions and
      patient satisfaction that provide valuable data regarding pain care nationwide.
      This study will review the results from the pain questions from this available
      data set and evaluate the performance of these hospitals in pain care in
      relationship to patient satisfaction. Furthermore, this analysis will be
      providing valuable information on how hospital size, geographic location and
      practice setting may play a role in pain care in US hospitals. RESULTS: The data
      indicates that 63% of patients gave a high rating of global satisfaction for
      their care, and that an additional 26% of patients felt that they had a moderate
      level of global satisfaction with the global quality of their care. When
      correlated to satisfaction with pain control, the relationship with global
      satisfaction and "always" receiving good pain control was highly correlated (r
      >0.84). In respect to the other HCAHPS components, we found that the patient and
      health care staff relationship with the patient is also highly correlated with
      pain relief (r >0.85). The patients' reported level of pain relief was
      significantly different based upon hospital ownership, with government owned
      hospitals receiving the highest pain relief, followed by nonprofit hospitals, and
      lastly proprietary hospitals. Hospital care acuity also had an impact on the
      patient's perception of their pain care; patients cared for in acute care
      hospitals had lower levels of satisfaction than critical access hospitals.
      CONCLUSIONS: The results of this study are a representation of the experiences of
      patients in US hospitals with regard to pain care specifically and the need for
      improved methods of treating and evaluating pain care. This study provides the
      evidence needed for hospitals to make pain care a priority in to achieve patient
      satisfaction throughout the duration of their hospitalization. Furthermore,
      future research should be developed to make strategies for institutions and
      policy-makers to improve and optimize patient satisfaction with pain care.

PMID- 21197303
TI  - Components of effective randomized controlled trials of hydrotherapy programs for
      fibromyalgia syndrome: A systematic review.
AB  - AIM: Previous systematic reviews have found hydrotherapy to be an effective
      management strategy for fibromyalgia syndrome (FMS). The aim of this systematic
      review was to summarize the components of hydrotherapy programs used in
      randomized controlled trials. METHOD: A systematic review of randomized
      controlled trials was conducted. Only trials that have reported significant FMS
      related outcomes were included. Data relating to the components of hydrotherapy
      programs (exercise type, duration, frequency and intensity, environmental
      factors, and service delivery) were analyzed. RESULTS: Eleven randomized
      controlled trials were included in this review. Overall, the quality of trials
      was good. Aerobic exercise featured in all 11 trials and the majority of
      hydrotherapy programs included either a strengthening or flexibility component.
      Great variability was noted in both the environmental components of hydrotherapy
      programs and service delivery. CONCLUSIONS: Aerobic exercise, warm up and cool
      down periods and relaxation exercises are common features of hydrotherapy
      programs that report significant FMS-related outcomes. Treatment duration of 60
      minutes, frequency of three sessions per week and an intensity equivalent to 60%
      80% maximum heart rate were the most commonly reported exercise components.
      Exercise appears to be the most important component of an effective hydrotherapy
      program for FMS, particularly when considering mental health-related outcomes.

PMID- 21197301
TI  - Recent advances in the use of opioids for cancer pain.
AB  - Opioids are the mainstay of treatment for moderate to severe cancer pain. In
      recent years there have been many advances in the use of opioids for cancer pain.
      Availability and consumption of opioids have increased and opioids other than
      morphine (including methadone, fentanyl, oxycodone) have become more widely used.
      Inter-individual variation in response to opioids has been identified as a
      significant challenge in the management of cancer pain. Many studies have been
      published demonstrating the benefits of opioid switching as a clinical maneuver
      to improve tolerability. Constipation has been recognized as a significant burden
      in cancer patients on opioids. Peripherally restricted opioid antagonists have
      been developed for the prevention and management of opioid induced constipation.
      The phenomenon of breakthrough pain has been characterized and novel modes of
      opioid administration (transmucosal, intranasal, sublingual) have been explored
      to facilitate improved management of breakthrough cancer pain. Advances have also
      been made in the realm of molecular biology. Pharmacogenetic studies have
      explored associations between clinical response to opioids and genetic variation
      at a DNA level. To date these studies have been small but future research may
      facilitate prospective prediction of response to individual drugs.

PMID- 21197304
TI  - Tapentadol immediate release: a new treatment option for acute pain management.
AB  - The undertreatment of acute pain is common in many health care settings.
      Insufficient management of acute pain may lead to poor patient outcomes and
      potentially life-threatening complications. Opioids provide relief of moderate to
      severe acute pain; however, therapy with pure MU-opioid agonists is often limited
      by the prevalence of side effects, particularly opioid-induced nausea and
      vomiting. Tapentadol is a novel, centrally acting analgesic with 2 mechanisms of
      action, MU-opioid receptor agonism and norepinephrine reuptake inhibition. The
      analgesic effects of tapentadol are independent of metabolic activation and
      tapentadol has no active metabolites; therefore, in theory, tapentadol may be
      associated with a low potential for interindividual efficacy variations and drug
      drug interactions. Previous phase 3 trials in patients with various types of
      moderate to severe acute pain have shown that tapentadol immediate release (IR;
      50 to 100 mg every 4 to 6 hours) provides analgesia comparable to that provided
      by the pure MU-opioid agonist comparator, oxycodone HCl IR (10 or 15 mg every 4
      to 6 hours), with a lower incidence of nausea, vomiting, and constipation.
      Findings suggest tapentadol may represent an improved treatment option for acute
      pain.

PMID- 21197305
TI  - Postdural puncture headache and pregabalin.
AB  - BACKGROUND: Even if carried out under optimal conditions, postdural puncture
      headache is still a frustrating and unpleasant complication in spinal anesthesia.
      This syndrome has an estimated incidence from less than 1% to about 5% of
      patients undergoing spinal anesthesia, even in the highest risk subset, the
      young, female, and pregnant population. CASE PRESENTATION: In our two female
      cases, headaches started following spinal anesthesia on the 11th and 14th hours,
      respectively. No response was obtained from patients diagnosed with postdural
      puncture headache with classical treatments such as bed rest, hydration, oral
      analgesic, and caffeine combination as well as intravenous theophylline
      application. The treatment of oral pregablin, commonly used for cases that
      rejected epidural blood patch, caused a significant decrease in headache
      severity. Later, the two cases whose headaches were completely resolved were
      discharged from the hospital on the post-operative 7th day. CONCLUSION: Postdural
      puncture headache is one of the most common complications of spinal anesthesia.
      Cerebral spinal fluid leakage into the epidural space has been proposed as the
      main mechanism responsible for this syndrome. Multiple methods of treatment have
      been applied with wide-ranging results. We detected that oral pregabalin
      application caused a significant decrease in the difficult and severe postdural
      puncture headaches of both our cases who did not respond to conventional
      treatments.

PMID- 21197306
TI  - Milnacipran for the management of fibromyalgia syndrome.
AB  - Fibromyalgia syndrome (FMS) is a widespread pain condition associated with
      fatigue, cognitive dysfunction, sleep disturbance, depression, anxiety, and
      stiffness. Milnacipran is one of three medications currently approved by the Food
      and Drug Administration in the United States for the management of adult FMS
      patients. This review is the second in a three-part series reviewing each of the
      approved FMS drugs and serves as a primer on the use of milnacipran in FMS
      treatment including information on pharmacology, pharmacokinetics, safety and
      tolerability. Milnacipran is a mixed serotonin and norepinephrine reuptake
      inhibitor thought to improve FMS symptoms by increasing neurotransmitter levels
      in descending central nervous system inhibitory pathways. Milnacipran has proven
      efficacy in managing global FMS symptoms and pain as well as improving symptoms
      of fatigue and cognitive dysfunction without affecting sleep. Due to its
      antidepressant activity, milnacipran can also be beneficial to FMS patients with
      coexisting depression. However, side effects can limit milnacipran tolerability
      in FMS patients due to its association with headache, nausea, tachycardia, hyper-
      and hypotension, and increased risk for bleeding and suicidality in at-risk
      patients. Tolerability can be maximized by starting at low dose and slowly up
      titrating if needed. As with all medications used in FMS management, milnacipran
      works best when used as part of an individualized treatment regimen that includes
      resistance and aerobic exercise, patient education and behavioral therapies.

PMID- 21197307
TI  - Supra-threshold scaling, temporal summation, and after-sensation: relationships
      to each other and anxiety/fear.
AB  - This study investigated the relationship of thermal pain testing from three types
      of quantitative sensory testing (ie, supra-threshold stimulus response scaling,
      temporal summation, and after-sensation) at three anatomical sites (ie, upper
      extremity, lower extremity, and trunk). Pain ratings from these procedures were
      also compared with common psychological measures previously shown to be related
      to experimental pain responses and consistent with fear-avoidance models of pain.
      Results indicated that supra-threshold stimulus response scaling, temporal
      summation, and after-sensation, were significantly related to each other. The
      site of stimulation was also an important factor, with the trunk site showing the
      highest sensitivity in all three quantitative sensory testing procedures. Supra
      threshold response measures were highly related to measures of fear of pain and
      anxiety sensitivity for all stimulation sites. For temporal summation and after
      sensation, only the trunk site was significantly related to anxiety sensitivity,
      and fear of pain, respectively. Results suggest the importance of considering
      site of stimulation when designing and comparing studies. Furthermore,
      psychological influence on quantitative sensory testing is also of importance
      when designing and comparing studies. Although there was some variation by site
      of stimulation, fear of pain and anxiety sensitivity had consistent influences on
      pain ratings.

PMID- 21197308
TI  - An open-label, non-randomized comparison of venlafaxine and gabapentin as
      monotherapy or adjuvant therapy in the management of neuropathic pain in patients
      with peripheral neuropathy.
AB  - Although many therapies are used in the management of neuropathic pain (NeP) due
      to polyneuropathy (PN), few comparison studies exist. We performed a prospective,
      non-randomized, unblended, efficacy comparison of the serotonin-norepinephrine
      reuptake inhibitor venlafaxine, as either monotherapy or adjuvant therapy, with a
      first-line medication for NeP, gabapentin, in patients with PN-related NeP. VAS
      pain scores were assessed after 3 and 6 months in intervention groups and in a
      cohort of patients receiving no pharmacotherapy. In a total of 223 patients, we
      analyzed pain quantity and quality (visual analogue scale [VAS] score, Brief Pain
      Inventory [BPI]), quality of life and health status measures [EuroQol 5 Domains,
      EQ-5D], Medical Outcomes Sleep Study Scale [MOSSS], Hospital Anxiety and
      Depression Scale [HADS] and Short Form 36 Health Survey [SF-36]) after 6 months
      of therapy. Significant improvements in VAS pain scores occurred for all
      treatment groups after 6 months. Improvements in aspects of daily life and
      anxiety were identified in all treatment groups. Our data suggest that
      monotherapy or adjuvant therapy with venlafaxine is comparable to gabapentin for
      NeP management. We advocate for head-to-head, randomized, double-blinded studies
      of current NeP therapies.

PMID- 21197309
TI  - Intra-articular hyaluronans: the treatment of knee pain in osteoarthritis.
AB  - The etiology of pain in osteoarthritis is multifactoral, and includes mechanical
      and inflammatory processes. Intra-articular injections of hyaluronans (HAs) are
      indicated when non-pharmacological and simple analgesics have failed to relieve
      symptoms. The HAs appear to reduce pain by restoring both mechanical and
      biomechanical homeostasis in the joint. There are five FDA-approved injectable
      preparations of HAs: Hyalgan((r)), Synvisc((r)), Supartz((r)), Orthovisc((r)) and
      Euflexxa((r)). They all appear to relieve pain from 4 to 14 weeks after injection
      and may have disease-modification properties. Although several randomized
      controlled trials have established the efficacy of this treatment modality,
      additional high quality randomized control studies with appropriate comparison
      are still required to clearly define the role of intra-articular HA injections in
      the treatment of osteoarthritis.

PMID- 21197310
TI  - What is adolescent low back pain? Current definitions used to define the
      adolescent with low back pain.
AB  - Adolescent low back pain (ALBP) is a common form of adolescent morbidity which
      remains poorly understood. When attempting a meta-analysis of observational
      studies into ALBP, in an effort to better understand associated risk factors, it
      is important that the studies involved are homogenic, particularly in terms of
      the dependent and independent variables. Our preliminary reading highlighted the
      potential for lack of homogeneity in descriptors used for ALBP. This review
      identified 39 studies of ALBP prevalence which fulfilled the inclusion criteria,
      ie, English language, involving adolescents (aged 10 to 19 years), pain localized
      to lumbar region, and not involving specific subgroups such as athletes and
      dancers. Descriptions for ALBP used in the literature were categorized into three
      categories: general ALBP, chronic/recurrent ALBP, and severe/disabling ALBP.
      Whilst the comparison of period prevalence rates for each category suggest that
      the three represent different forms of ALBP, it remains unclear whether they
      represented different stages on a continuum, or represent separate entities. The
      optimal period prevalence for ALBP recollection depends on the category of ALBP.
      For general ALBP the optimal period prevalence appears to be up to 12 months,
      with average lifetime prevalence rates similar to 1-year prevalence rates,
      suggesting an influence of memory decay on pain recall.

PMID- 21197311
TI  - Intravenous ibuprofen: the first injectable product for the treatment of pain and
      fever.
AB  - This paper reviews the current data on the use of the first approved intravenous
      ibuprofen product for the management of post-operative pain and fever in the
      United States. The management of acute and post-operative pain and fever with
      nonsteroidal anti-inflammatory agents (NSAIDs) is well documented. A search in
      Medline and International Pharmaceutical Abstracts of articles until the end of
      November 2009 and references of all citations were conducted. Available
      manufacturer data on file were also analyzed for this report. Several randomized
      controlled studies have demonstrated the opioid-sparing and analgesic effects of
      400 and 800 mg doses of intravenous ibuprofen in a series of post-operative
      patient populations. Two recent studies have also noted the improvement in fever
      curves in critically ill and burn patients. These data, along with
      pharmacokinetic and pharmacologic properties, are explored in this review, which
      addresses the clinical utility of a parenteral NSAID in a hospitalized patient
      for post-operative pain management and fever reduction. Further data on
      intravenous ibuprofen are needed to define long-term utilization, management of
      acute pain, and use in special populations.

PMID- 21197312
TI  - Pregabalin for the management of fibromyalgia syndrome.
AB  - This last article in a three-part series on approved medications for managing
      fibromyalgia syndrome (FMS) reviews pregabalin (Lyrica((r))). Pregabalin was the
      first drug approved for FMS management and, as an anticonvulsant, differs from
      the other approved agents that are antidepressants. Pregabalin inhibits
      presynaptic excitatory neurotransmitter release by blocking alpha(2)delta calcium
      channels. Five randomized, placebo-controlled trials have demonstrated pregabalin
      reduces pain and improves sleep and health-related quality of life in FMS
      patients. While indicated dosing is 300-450 mg divided twice daily, initial
      dosing of 25-50 mg at night is recommended owing to side effects including
      somnolence, dizziness, and cognitive dysfunction. Since side effects such as
      weight gain and peripheral edema are dose-related, uptitration in weekly
      increments based on tolerability and therapeutic response is recommended. Due to
      its lack of protein binding and negligible hepatic metabolism, pregabalin can be
      safely combined with other medications and used in patients with renal failure
      when the dose is appropriate. Pregabalin may worsen sedation when combined with
      central nervous system depressants. Pregabalin should be discontinued gradually.
      Pregabalin-treated patients should be monitored for the emergence or worsening of
      depression, suicidal thoughts or behavior. Pregabalin in combination with the
      other approved medications may be synergistic in treating FMS.

PMID- 21197313
TI  - New and emerging therapeutic agents for the treatment of fibromyalgia: an update.
AB  - Fibromyalgia (FM) is a chronic widespread pain condition that is estimated to
      affect 5 million US adults. Several molecular pathophysiologies are thought to
      contribute to the symptoms of FM, complicating the development of effective
      clinical management techniques. It is now known that abnormalities in both
      nociceptive and central pain processing systems are necessary (but perhaps not
      sufficient) to condition the onset and maintenance of FM, producing associated
      neuropsychologic symptoms such as pronounced fatigue, sleep abnormalities,
      cognitive difficulties, stress sensitivity, anxiety, and depression. Current
      treatment strategies are focused primarily on correcting the pathophysiologic
      mechanisms underlying these nervous system abnormalities. Clinical studies
      demonstrate the safety and efficacy of three drugs recently approved for the
      treatment of FM: pregabalin (an alpha-2-delta ligand), and duloxetine and
      milnacipran (serotonin/norepinephrine reuptake inhibitors). This review describes
      these pharmaceuticals in detail and discusses their current roles in FM
      management.

PMID- 21197315
TI  - Comparison of the effects of dietary factors in the management and prophylaxis of
      migraine.
AB  - Migraine is defined as a disorder characterized by intermittent headache
      episodes, accompanied with nausea, photophobia and/or phonophobia.
      Pharmacological therapy is in accordance with the severity of pain and may
      include acute, prophylactic and most commonly both approaches. The aim of the
      acute therapy is stopping or alleviating the attack or progression of the pain
      and, in case of a migraine attack that has started, lessening the pain.
      Preventive therapy aims to reduce attack frequency and severity. This study was
      designed to evaluate the effect of dietary factors in the management and
      prophylaxis of migraine in cases diagnosed as having migraine disorder according
      to the 2003-IHS criteria. Fifty consecutive Turkish patients (13 men, 37 women)
      with diagnosis of migraine were randomly divided into two groups for treatment
      protocols with the written approval of the ethics committee. The cases in the
      first group (K) were treated with metoprolol, vitamin B(2) (riboflavin), and
      naproxen sodium just at the aura or at the beginning of the attacks. The cases in
      the second group (D) were also supplied with a comprehensive dietary list
      arranged by our algology clinic in addition to the same medication protocol.
      There were no demographic differences between the cases (P > 0.05). VAS scores
      were lower in group D than group K (P < 0.01), and also the migraine attack
      frequencies and monthly amounts of analgesic consumed amounts were also
      statistically significantly less. It was concluded that beta-blocker and
      riboflavin therapy supplemented with a convenient diet with appropriate
      alternatives in patients with migraine disorder was associated with statistically
      significant decreases in headache frequency, intensity, duration and medication
      intake.

PMID- 21197314
TI  - Acute pain management in children.
AB  - The greatest advance in pediatric pain medicine is the recognition that untreated
      pain is a significant cause of morbidity and even mortality after surgical
      trauma. Accurate assessment of pain in different age groups and the effective
      treatment of postoperative pain is constantly being refined; with newer drugs
      being used alone or in combination with other drugs continues to be explored.
      Several advances in developmental neurobiology and pharmacology, knowledge of new
      analgesics and newer applications of old analgesics in the last two decades have
      helped the pediatric anesthesiologist in managing pain in children more
      efficiently. The latter include administering opioids via the skin and nasal
      mucosa and their addition into the neuraxial local anesthetics. Systemic opioids,
      nonsteroidal anti-inflammatory agents and regional analgesics alone or combined
      with additives are currently used to provide effective postoperative analgesia.
      These modalities are best utilized when combined as a multimodal approach to
      treat acute pain in the perioperative setting. The development of receptor
      specific drugs that can produce pain relief without the untoward side effects of
      respiratory depression will hasten the recovery and discharge of children after
      surgery. This review focuses on the overview of acute pain management in
      children, with an emphasis on pharmacological and regional anesthesia in
      achieving this goal.

PMID- 21197316
TI  - Musculoskeletal pain: prescription of NSAID and weak opioid by primary health
      care physicians in Sweden 2004-2008 - a retrospective patient record review.
AB  - PURPOSE: To study the prescription of oral analgesics for musculoskeletal pain by
      primary care physicians over a 5-year period in Sweden. DESIGN: A retrospective
      automatic database review of patient records at four primary health care centers.
      All prescriptions of NSAIDs, weak opioids, and coprescriptions of
      gastroprotecting medications to patients with musculoskeletal were retrieved for
      the period January 1, 2004 to November 11, 2008. RESULTS: A total of 27,067
      prescriptions prescribed to 23,457 patients with musculoskeletal pain were
      analyzed. Of all prescriptions, NSAIDs were the most commonly prescribed
      analgesic comprising 79%, tramadol was the second most commonly prescribed
      analgesic comprising 9%, codeine the third most (7%), and dextropropoxyphene the
      fourth (5%). The proportion of NSAIDs and weak opioids and the proportion of the
      different weak opioids prescribed showed no change over time. The proportion of
      nonselective and selective NSAIDs prescribed changed; Coxib prescriptions
      decreased from 9% to 4% of all analgesics prescribed in 2004-2007 with no change
      in 2008. CONCLUSION: NSAIDs were found to be the dominant class of analgesic
      prescribed by primary care physicians to patients diagnosed as musculoskeletal
      pain. No change was observed in the proportion of NSAID and weak opioid
      prescription over the period studied. Prescription of selective Coxibs decreased
      and was less than 4% in 2008. The impact on gastrointestinal and cardiovascular
      adverse effects associated with the extensive prescription of NSAIDS for
      musculoskeletal pain warrants further analysis.

PMID- 21197317
TI  - Pillow use: the behavior of cervical stiffness, headache and scapular/arm pain.
AB  - BACKGROUND: Pillows are intended to support the head and neck in a neutral
      position to minimize biomechanical stresses on cervical structures whilst
      sleeping. Biomechanical stresses are associated with waking cervical symptoms.
      This paper adds to the scant body of research investigating whether different
      pillow types produce different types and frequencies of waking symptoms in
      asymptomatic subjects. METHODS: A random-allocation block-design blinded field
      trial was conducted in a large South Australian regional town. Subjects were side
      sleepers using one pillow only, and not receiving treatment for cervicothoracic
      problems. Waking cervical stiffness, headache and scapular/arm pain were recorded
      daily. Five experimental pillows (polyester, foam regular, foam contour, feather,
      and latex) were each trialed for a week. Subjects' 'own' pillow was the control
      (a baseline week, and a washout week between each experimental pillow trial
      week). Subjects reported waking symptoms related to known factors (other than the
      pillow), and subjects could 'drop out' of any trial pillow week. RESULTS:
      Disturbed sleep unrelated to the pillow was common. Waking symptoms occurring at
      least once in the baseline week were reported by approximately 20% of the
      subjects on their 'own' pillow. The feather trial pillow performed least well,
      producing the highest frequency of waking symptoms, while the latex pillow
      performed best. The greatest number of 'drop outs' occurred on the feather
      pillow. The foam contour pillow performed no better than the foam regular pillow.
      CONCLUSION: 'Own' pillows did not guarantee symptom-free waking, and thus were a
      questionable control. The trial pillows had different waking symptom profiles.
      Latex pillows can be recommended over any other type for control of waking
      headache and scapular/arm pain.

PMID- 21197318
TI  - Pilot study: rapidly cycling hypobaric pressure improves pain after 5 days in
      adiposis dolorosa.
AB  - Adiposis dolorosa (AD) is a rare disorder of painful nodular subcutaneous fat
      accompanied by fatigue, difficulty with weight loss, inflammation, increased
      fluid in adipose tissue (lipedema and lymphedema), and hyperalgesia. Sequential
      compression relieves lymphedema pain; we therefore hypothesized that whole body
      cyclic pneumatic hypobaric compression may relieve pain in AD. To avoid
      exacerbating hyperalgesia, we utilized a touch-free method, which is delivered
      via a high-performance altitude simulator, the Cyclic Variations in Altitude
      ConditioningTM (CVACTM) process. As a pilot study, 10 participants with AD
      completed pain and quality of life questionnaires before and after 20-40 minutes
      of CVAC process daily for 5 days. Participants lost weight (195.5 +/- 17.6-193.8
      +/- 17.3 lb; P = 0.03), and bioimpedance significantly decreased (510 +/- 36-490
      +/- 38 ohm; P = 0.01). There was a significant decrease in scores on the Pain
      Catastrophizing Scale (P = 0.039), in average (P = 0.002), highest (P = 0.029),
      lowest (P = 0.04), and current pain severity (P = 0.02) on the Visual Analogue
      Scale, but there was no change in pain quality by the McGill Pain Questionnaire.
      There were no significant changes in total and physical SF-36 scores, but the
      mental score improved significantly (P = 0.049). There were no changes in the
      Pain Disability Index or Pittsburgh Sleep Quality Index. These data present a
      potential, new, noninvasive means of treating pain in AD by whole body pneumatic
      compression as part of the CVAC process. Although randomized, controlled trials
      are needed to confirm these data, the CVAC process could potentially help in
      treating AD pain and other chronic pain disorders.

PMID- 21197319
TI  - Daily smoking and lower back pain in adult Canadians: the Canadian Community
      Health Survey.
AB  - BACKGROUND: Lower back pain (LBP) is one of the primary causes of disability in
      the Canadian community. However, only a limited number of studies have addressed
      the association between daily smoking and LBP in Canada. Of the studies that have
      explored this association, many had small sample sizes and failed to control for
      confounders. OBJECTIVE: The primary objective of the study was to determine if
      daily smoking is associated with an increased risk of having LBP. The secondary
      objectives were to assess the risk for LBP among occasional smokers and to
      determine the prevalence of LBP in relation to different covariates. DATA AND
      STUDY DESIGN: Using the Canadian Community Health Survey (cycle 3.1) data, 73,507
      Canadians between the ages of 20 and 59 years were identified. LBP status,
      smoking level, sex, age, body mass index (BMI), level of activity and level of
      education were assessed in these subjects. METHODS: Stratified analysis and
      logistic regression analysis were used to detect effect modifications and to
      adjust for covariates. Population weight and design were taken into
      consideration. RESULTS: The prevalence of LBP was 23.3% among daily smokers and
      15.7% among non-smokers. Age and sex were found to be effect modifiers. The
      association between LBP and daily smoking was statistically significant in all
      ages and genders; this association was stronger for younger age groups. The
      adjusted odds ratio for male daily smokers aged 20 to 29 was 1.87 (95% CI = 1.62,
      2.17); findings were similar for women. Occasional smoking slightly increased the
      odds of having back pain. CONCLUSION: Young Canadian daily smokers are at higher
      risk for LBP. This study also suggests a positive correlation between smoking
      dose and the risk of LBP. These findings indicate that smoking behavioral
      modification may have an impact on reducing back pain especially among young
      adults.

PMID- 21197320
TI  - Analgesic effects of intra-articular botulinum toxin Type B in a murine model of
      chronic degenerative knee arthritis pain.
AB  - OBJECTIVE: To evaluate the analgesic effectiveness of intra-articular botulinum
      toxin Type B (BoNT/B) in a murine model of chronic degenerative arthritis pain.
      METHODS AND MATERIALS: Chronic arthritis was produced in adult C57Bl6 mice by
      intra-articular injection of Type IV collagenase into the left knee. Following
      induction of arthritis, the treatment group received intra-articular BoNT/B.
      Arthritic control groups were treated with intra-articular normal saline or sham
      injections. Pain behavior testing was performed prior to arthritis, after
      induction of arthritis, and following treatments. Pain behavior measures included
      analysis of gait impairment (spontaneous pain behavior) and joint tenderness
      evaluation (evoked pain response). Strength was measured as ability to grasp and
      cling. RESULTS: Visual gait analysis showed significant impairment of gait in
      arthritic mice that improved 43% after intra-articular BoNT/B, demonstrating a
      substantial articular analgesic effect. Joint tenderness, measured with evoked
      pain response scores, increased with arthritis induction and decreased 49.5%
      after intra-articular BoNT/B treatment. No improvement in visual gait scores or
      decrease in evoked pain response scores were found in the control groups
      receiving intra-articular normal saline or sham injections. Intra-articular
      BoNT/B was safe, and no systemic effects or limb weakness was noted. CONCLUSIONS:
      This study is the first report of intra-articular BoNT/B for analgesia in a
      murine model of arthritis pain. The results of this study validate prior work
      using intra-articular neurotoxins in murine models. Our findings show chronic
      degenerative arthritis pain can be quantitated in a murine model by measuring
      gait impairment using visual gait analysis scores (spontaneous pain behavior) and
      joint tenderness scores (evoked pain responses). Reduction of joint pain seen in
      this study is consistent with our hypothesis of inhibition of release of pain
      mediators by intra-articular BoNT/B, supporting further investigation of this
      novel approach to treatment of arthritis pain with intra-articular neurotoxins.

PMID- 21197321
TI  - Investigational pharmacology for low back pain.
AB  - STUDY DESIGN: Review and reinterpretation of existing literature. OBJECTIVE: This
      review article summarizes the anatomy and pathogenesis of disease processes that
      contribute to low back pain, and discusses key issues in existing therapies for
      chronic low back pain. The article also explains the scientific rationale for
      investigational pharmacology and highlights emerging compounds in late
      development. RESULTS/CONCLUSION: While the diverse and complex nature of chronic
      low back pain continues to challenge clinicians, a growing understanding of
      chronic low back pain on a cellular level has refined our approach to managing
      chronic low back pain with pharmacology. Many emerging therapies with improved
      safety profiles are currently in the research pipeline and will contribute to a
      multimodal therapeutic algorithm in the near future. With the heterogeneity of
      the patient population suffering from chronic low back pain, the clinical
      challenge will be accurately stratifying the optimal pharmacologic approach for
      each patient.

PMID- 21197322
TI  - Opioid chronopharmacology: influence of timing of infusion on fentanyl's
      analgesic efficacy in healthy human volunteers.
AB  - Chronopharmacology studies the effect of the timing of drug administration on
      drug effect. Here, we measured the influence of 4 timing moments on fentanyl
      induced antinociception in healthy volunteers. Eight subjects received 2.1 MUg/kg
      intravenous fentanyl at 2 pm and 2 am, with at least 2 weeks between occasions,
      and 8 others at 8 am and 8 pm. Heat pain measurements using a thermode placed on
      the skin were taken at regular intervals for 3 hours, and verbal analog scores
      (VAS) were then obtained. The data were modeled with a sinusoid function using
      the statistical package NONMEM. The study was registered at trialregister.nl
      under number NTR1254. A significant circadian sinusoidal rhythm in the
      antinociceptive effect of fentanyl was observed. Variations were observed for
      peak analgesic effect, duration of effect, and the occurrence of hyperalgesia. A
      peak in pain relief occurred late in the afternoon (5:30 pm) and a trough in the
      early morning hours (5:30 am). The difference between the peak and trough in pain
      relief corresponds to a difference in VAS of 1.3-2 cm. Only when given at 2 am,
      did fentanyl cause a small but significant period of hyperalgesia following
      analgesia. No significant changes were observed for baseline pain, sedation, or
      the increase in end-tidal CO(2). The variations in fentanyl's antinociceptive
      behavior are well explained by a chronopharmacodynamic effect originating at the
      circadian clock in the hypothalamus. This may be a direct effect through shared
      pathways of the circadian and opioid systems or an indirect effect via diurnal
      variations in hormones or endogenous opioid peptides that rhythmically change the
      pain response and/or analgesic response to fentanyl.

PMID- 21197323
TI  - Extended-release morphine sulfate in treatment of severe acute and chronic pain.
AB  - Morphine is the archetypal opioid analgesic. Because it is a short-acting opioid,
      its use has been limited to the management of acute pain. The development of
      extended-release formulations have resulted in the increased utilization of
      morphine in chronic pain conditions. This review documents the history of
      morphine use in pain treatment, and describes the metabolism, pharmacodynamics,
      formulations, and efficacy of the currently available extended-release morphine
      medications.

PMID- 21197324
TI  - Effectiveness of the association between carbamazepine and peripheral analgesic
      block with ropivacaine for the treatment of trigeminal neuralgia.
AB  - Treatment of trigeminal neuralgia (TN) is achieved by using adjuvant analgesics
      like antiepileptics, with carbamazepine (CBZ) being the first-line approach for
      TN patients, although side effects may be present. Other approaches using
      gabapentin, namely when associated with peripheral analgesic block of TN trigger
      points with the local anesthetic ropivacaine (ROP), resulted in decreased pain
      and daily drug intake (reduced side effects). This study evaluates if the
      association between CBZ and the peripheral block with ROP reinforces the clinical
      value of CBZ. In this parallel, double-blinded study, idiopathic TN patients were
      randomized to receive during 4 weeks either CBZ (CBZ; n = 21) or CBZ associated
      with the peripheral analgesic block using ROP (CBZ + ROP; n = 24). The primary
      outcome measures were the following: i) pain intensity, evaluated by the
      numerical rating scale; ii) number of pain crises; and iii) number needed to
      treat. Evaluation points were at the beginning (day 1) and end (day 29) of
      treatment and after a follow-up of 5 months (month 6). Both protocols resulted in
      a decrease of pain intensity and number of pain crises, but only the association
      CBZ + ROP showed i) a significant stronger reduction in pain intensity at month 6
      and ii) a significant decrease in the daily dose of CBZ given to patients (both
      at day 29 and month 6). In contrast, the daily dose in CBZ-only patients remained
      constant or even increased. The number needed to treat for the association CBZ +
      ROP over the CBZ protocol reduced from 5 at the end of the 4-week treatment to 3
      after the 5-month follow-up. Data reinforce the use of CBZ as a primary tool to
      control pain in TN patients, as the association CBZ + ROP i) improves the
      clinical qualities of CBZ, ii) strongly reduces the daily dose of CBZ, and iii)
      reduces the potential side effects attributed to high doses of CBZ.

PMID- 21197325
TI  - Characterization of a rat model of metastatic prostate cancer bone pain.
AB  - PURPOSE: The objectives of this study were to establish and characterize a novel
      animal model of metastatic prostate cancer-induced bone pain. METHODS: Copenhagen
      rats were injected with 10(6) MATLyLu (MLL) prostate cancer cells or phosphate
      buffered saline by per cutaneous intra femoral injections into the right hind leg
      distal epiphysis. Over 13 days, rats progressively developed a tumor within the
      distal femoral epiphysis. On days 3, 7, 10, and 13 post injection, rats were
      subjected to the incapacitance and Randall-Selitto behavioral tests as they are
      believed to be indirect reflections of tumor induced pain. Ipsilateral hind limbs
      were subjected to X-ray and computed tomography (CT) scans and histological
      sections were stained with hematoxylin and eosin (H&E). RESULTS: Intra femoral
      injections of MLL cells resulted in the progressive development of a tumor
      leading to bone destruction and nociceptive behaviors. Tumor development resulted
      in the redistribution of weight to the contralateral hind leg and significantly
      reduced the paw withdrawal threshold of the ipsilateral hind paw as observed via
      the incapacitance and Randall-Selitto tests, respectively. X-ray and computed
      tomography scans along with H&E stains indicated tumor-associated structural
      damage to the distal femur. This model was challenged with administration of
      meloxicam. Compared with vehicle-injected controls, the meloxicam-treated rats
      displayed smaller nociceptive responses as observed with the incapacitance and
      Randall-Selitto tests, suggesting that meloxicam was effective in reducing the
      pain-related symptoms displayed by model animals and that the model behaved in a
      predictable way to cyclooxygenase-2 treatment. CONCLUSIONS: This model is unique
      from other bone cancer models in that it is a comprehensive model utilizing a
      competent immune system with a syngeneic tumor. The model establishes a tool that
      will be useful to investigate mechanisms of cancer pain that are induced by
      cancer cells.

PMID- 21197326
TI  - Topical nonsteroidal anti-inflammatory drugs for the treatment of pain due to
      soft tissue injury: diclofenac epolamine topical patch.
AB  - The objective of this article is to review published clinical data on diclofenac
      epolamine topical patch 1.3% (DETP) in the treatment of acute soft tissue
      injuries, such as strains, sprains, and contusions. Review of published
      literature on topical nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac,
      and DETP in patients with acute soft tissue injuries was included. Relevant
      literature was identified on MEDLINE using the search terms topical NSAIDs,
      diclofenac, diclofenac epolamine, acute pain, sports injury, soft tissue injury,
      strain, sprain, and contusion, and from citations in retrieved articles covering
      the years 1978-2008. Review of published, randomized clinical trials and meta
      analyses shows that topical NSAIDs are significantly more effective than placebo
      in relieving acute pain; the pooled average relative benefit was 1.7 (95%
      confidence interval, 1.5-1.9). In a limited number of comparisons, topical and
      oral NSAIDs provided comparable pain relief, but the use of topical agents
      produced lower plasma drug concentrations and fewer systemic adverse events
      (AEs). The physical-chemical properties of diclofenac epolamine make it well
      suited for topical use. In patients with acute soft tissue injuries treated with
      DETP, clinical data report an analgesic benefit within hours of the first
      application, and significant pain relief relative to placebo within 3 days.
      Moreover, DETP displayed tolerability comparable with placebo; the most common
      AEs were pruritus and other application site reactions. Review of published
      literature suggests that DETP is generally safe and well tolerated, clinically
      efficacious, and a rational treatment option for patients experiencing acute pain
      associated with strains, sprains, and contusions, and other localized painful
      conditions.

PMID- 21197327
TI  - Constructing a nurse appraisal form: A Delphi technique study.
AB  - OBJECTIVE: The study was conducted with the aim to construct a unified nurse
      appraisal format to be used at hospitals performing under different healthcare
      organizations in the Eastern Province in the Kingdom of Saudi Arabia.
      METHODOLOGY: The study included hospitals representing different healthcare
      organizations within the Eastern Province. The target population included
      Hospital head nurses and nurse supervisors and the snowball sampling technique
      was employed to select the panel subjects. RESULTS: The final draft resulted into
      the agreed upon performance dimensions which included namely; quality standards,
      work habits, supervision/leadership, staff relations and interpersonal skills,
      attendance and punctuality, problem solving, oral communication, productivity
      results, coordination, innovation, record keeping. CONCLUSION: Nurse managers
      have to continuously assess competence of practicing nurses to assure qualified
      and safe patient care. A nurse appraisal form was constructed concurrently with
      this study results and was proposed to be used at all Eastern Region hospitals.
      This study is considered an initial step for further efforts and studies to be
      conducted to reach both national and international nursing appraisal dimensions
      and unify them for the sake of best health promotion.

PMID- 21197328
TI  - Laparoscopic bladder (Boari) flap ureteroneocystostomy.
AB  - Iatrogenic ureteric injuries in gynecologic surgery are quite common. The
      laparoscopic spectra of treatment gives a wide range of application. We present
      the case of a 40-year-old female who underwent total abdominal hysterectomy with
      bilateral salpingo-oopherectomy for dysfunctional uterine bleeding.
      Postoperatively, she had oliguria with raised creatinine and was found to have
      ureteric narrowing on magnetic resonance urogram. The patient was successfully
      managed by laparoscopic (Boari flap) ureteroneocystostomy.

PMID- 21197329
TI  - Transmission of communicable respiratory infections and facemasks.
AB  - BACKGROUND: Respiratory protection efficiency of facemasks is critically
      important in the battle against communicable respiratory infections such as
      influenza and severe acute respiratory syndrome (SARS). We studied the spatial
      distributions of simulated virus-laden respiratory droplets when human subjects
      wore facemasks and were exposed to regulatory viral droplets by conducting in
      vivo experiments in facemask use. METHODS: Transmission pathway of aerosols of
      Fluorescein-KCl solution through facemasks and protective efficiency of facemasks
      were examined by using normal surgical facemasks and two facemasks with exhaust
      valves (Facemask A) and exhaust holes (Facemask B) covered with the same surgical
      filters situated at the back of the facemasks. Fluorescein-KCl solution was
      sprayed onto the faces of participants wearing the facemasks and performing
      intermittent exercises on a treadmill in a climatic chamber. RESULTS:
      Experimental results showed that when droplets spread onto a person face-to-face
      over short distances, 92.3% to 99.5% of droplets were blocked by the front
      surface of the facemask, whereas only 0.5% to 7.7% of droplets reached the back
      of the facemask. Both facemasks A and B had near or over 99% protection
      efficiency, compared with that of 95.5% to 97% of surgical facemasks. Using the
      same filters as normal surgical masks, facemasks A and B provided more effective
      respiratory protection against communicable respiratory infections such as
      influenza and SARS by the location of the breathing pathway to the back of the
      facemasks. CONCLUSIONS: Separating the breathing pathway from the virus
      contaminated area in facemasks can provide more effective protection against
      communicable respiratory infections such as influenza and SARS.

PMID- 21197330
TI  - Competing interests in development of clinical practice guidelines for diabetes
      management: Report from a multidisciplinary workshop.
AB  - OBJECTIVE: To explore the complex issue of competing interests (CIs) in
      development of clinical practice guidelines (CPGs) in diabetes with stakeholders.
      METHODS: A multidisciplinary panel of 26 health, methodological, legal, and
      bioethical experts, trainees, and lay people from across Canada participated in a
      workshop on CIs in CPGs. Mixed methods were used such that qualitative themes
      were extracted from the discussions and quantitative survey data were collected.
      RESULTS: In the discussions, participants acknowledged that potential competing
      interests were not uncommon among sponsoring organizations and authors of CPGs.
      Avoidance of all potential CIs in development of CPGs was emulated as ideal, but
      considered probably unrealistic, given the paucity of peer-reviewed funding
      opportunities for development of evidence-informed CPGs and the scarcity of
      knowledgeable authors without CIs. An optimal approach for management of CIs in
      CPGs could not be agreed upon by participants. Full disclosure of any financial
      CIs for authors and sponsoring organizations as well as discouragement of
      external financial contributors from writing involvement, were endorsed by
      participants in the workshop and a subsequent survey. CONCLUSIONS: Complete
      disclosure of financial CIs of sponsoring organizations and authors of CPGs is
      essential, yet the optimal approach to management of potential CIs is currently
      undefined.

PMID- 21197331
TI  - Renegotiating roles as part of developing collaborative practice: Australian
      nurses in general practice and cervical screening.
AB  - This paper reports the findings from an action research study that used a
      reflective group method to work with nurses in general practice recently
      credentialed as cervical screeners. The research aimed to develop a new model of
      practice nurse service delivery within a multidisciplinary team. Findings
      demonstrated that poor interdisciplinary collaboration created barriers to
      changing the role of the practice nurse. Key themes identified were:
      renegotiating their roles, identifying and negotiating gendered patterns of
      cervical screening, and the effect of multidisciplinary teams and
      interdisciplinary collaboration on practice nurse retention. Recommendations from
      this study address the need for improved piloting of new initiatives and an
      increase in continuing professional development for practice managers who are
      potential change agents.

PMID- 21197332
TI  - Effectively using communication to enhance the provision of pediatric palliative
      care in an acute care setting.
AB  - The capability of effectively communicating is crucial when providing palliative
      care, especially when the patient is a child. Communication among healthcare
      professionals with the child and family members must be clear, concise, and
      consistent. Use of a communication tool provides documentation for conversations,
      treatment plans, and specific desires related to care. This paper describes
      communication theory, portrays the use of this theory to develop a communication
      tool, and illustrates the use of this tool by multidisciplinary members of a
      healthcare team to provide pediatric palliative care.

PMID- 21197333
TI  - Intention to stay and nurses' satisfaction dimensions.
AB  - OBJECTIVE: The study was conducted to identify the satisfaction dimensions in
      relation to anticipated nurse turnover in an academic medical institution using
      an ordinal regression model. METHODOLOGY: A cross-sectional descriptive study was
      designed to describe nurse job satisfaction in relation to their intention to
      stay at King Faisal University's Hospital, Al-Khobar, Saudi Arabia. All nurses
      available at the time of the study were included (499 nurses in different
      departments). The response rate was 55.3% (276 questionnaires suitable for
      analysis). A self-administered questionnaire with 26 items was developed for this
      study with a five-point Likert scale ranging from 1 = highly dissatisfied to 5 =
      highly satisfied). RESULTS: Nurses were least satisfied with the hospital's
      benefits (1.2 +/- 0.4), hospital policies (1.4 +/- 0.5), bonuses (1.1 +/- 0.3),
      fairness of the performance appraisal system (1.5 +/- 0.5) paid time off (1.5 +/-
      0.5), and recognition of achievements (1.5 +/- 0.5). The mean general job
      satisfaction score was 2.2 +/- 0.4. Ordinal regression analysis revealed
      leadership styles and challenging opportunities as predictive dimensions for the
      intention to stay. CONCLUSION: There are nurse job satisfaction dimensions other
      than salary and incentive that may be anticipated with the intention to stay in
      the health facility. Namely, leadership styles in the health organization and
      challenging opportunities at work.

PMID- 21197334
TI  - Soap-scented oil skin patch in the treatment of fibromyalgia: A case series.
AB  - Treatment for fibromyalgia is largely empiric and supportive, and favors a
      multidisciplinary approach. Despite treatment, symptomatic relief is often
      inadequate and temporary. Over 90% of fibromyalgia patients seek alternative
      medical care. There is much anecdotal evidence that applying a bar of soap to the
      skin can relieve leg cramps. Expanding on this idea, I created a skin patch from
      soap-scented oil, which was used to treat muscular pain and spasms. After
      receiving positive feedback from several patients, I hypothesized that the scent
      of the oil itself, applied directly to the skin, is responsible for the pain
      relieving and muscle-relaxant properties of the skin patch. Furthermore, I
      hypothesize that this soap-scented oil skin patch is an effective treatment for
      the pain associated with fibromyalgia.

PMID- 21197335
TI  - Nutritional issues in older adults with wounds in a clinical setting.
AB  - BACKGROUND: The ability for patients to access and consume sufficient quantities
      of nutrients to meet recommendations for wound management is vital if decline in
      nutritional status during hospital admission is to be prevented. This study aims
      to investigate menu quality, consumption patterns, and changes in nutritional
      status for inpatients with wounds. METHODS: Wound healing recommendations were
      compared against the nutrient content of the inpatient menu. Individual intakes
      were compared to estimated requirements: energy using the Schofield equation;
      protein using wound healing recommendations; vitamin A, C, and zinc using the
      recommended daily intake (RDI). RESULTS: The inpatient menu did not provide
      sufficient energy or zinc to meet the estimated average requirement while the
      ordering practices of participants allowed all RDI to be achieved except for
      zinc. Actual intake fell below recommendations: 62%, 41%, 55%, and 79% of
      patients not meeting energy, minimum protein requirements, vitamin A or zinc RDI
      respectively. A nonsignificant trend for weight loss, particularly fat mass, was
      observed over time. CONCLUSION: Inpatients with wounds are at risk of being
      unable to consume sufficient quantities of nutrients important for healing and
      prevention of decline in nutritional status. This is despite the menu seemingly
      providing sufficient nutrients. More attention to education, encouragement, and
      supplementation are recommended.

PMID- 21197336
TI  - Use of a multidisciplinary tool to achieve target outcomes in Native American
      patients with diabetes: Treat-to-target.
AB  - PURPOSE: Our purpose was to test a communication tool used in a multidisciplinary
      setting to more effectively achieve the recommended goals for glucose, blood
      pressure, lipids, and prophylactic aspirin use in a Native American population
      with type 2 diabetes. METHODS: One hundred randomly selected patients were
      included in this observational, pre-intervention, post-intervention study design.
      The team began with a chart audit documenting hemoglobin A(1c) (Hgb A(1c)), blood
      pressure, cholesterol levels, and aspirin use. The intervention included the
      development of a one page form used to prompt providers to intensify therapy when
      the patient was not meeting evidence-based goals. The audit was repeated one year
      later. RESULTS: Analysis of 74 patients completing the study showed a decrease in
      Hgb A1C from 8.812% pre-intervention to a mean 8.214% post-intervention (p <
      0.007). At the time of pre-intervention audit, patients were already at target
      for blood pressure and no significant further decrease was found. Measures of
      total cholesterol, triglycerides, and aspirin use showed improvement, but
      statistical significance was not met. CONCLUSION: The one-page multidisciplinary
      tool used to intensify therapy significantly improved glucose control. More
      consistent interaction of the multidisciplinary team is necessary to reach other
      desired goals.

PMID- 21197338
TI  - New perspectives in pediatric trauma care.
AB  - An "American-style" pediatric trauma care symposia consisting of lectures,
      workshops, and skill stations was held at a pediatric trauma center to improve
      pre- and post-hospital care for children, facilitate communication, and to set up
      standards within the regional rescue chain.

PMID- 21197337
TI  - Testosterone and growth hormone normalization: a retrospective study of health
      outcomes.
AB  - BACKGROUND: Age-related declines in testosterone and growth hormone (GH) are
      associated with increased adiposity and decreases in lean mass and bone mineral
      density (BMD). A long-term retrospective study examined the effects of
      testosterone and/or GH supplementation on body composition and quality of life
      (QoL). METHODS: A database survey assessed the records of 91 men and 97 women
      (ages 25-82) in treatment groups based on their hormonal status:
      dehydroepiandrosterone but no hormonal supplementation (control); testosterone
      only (Tes); GH only (GH); and testosterone plus GH (Tes+GH). Pre-and post
      treatment assessments recorded changes in fat and lean mass, BMD, and QoL.
      RESULTS: After an average of 3 years of treatment, weight decreased in women in
      the control and Tes+GH groups but remained stable in men in all groups. Tes and
      Tes+GH produced statistically significant increases in lean mass, reductions in
      fat mass, and improvements in BMD in both sexes; GH produced similar changes in
      women. QoL and mood improved in all groups. Treatments were generally safe and
      well tolerated. CONCLUSIONS: In this retrospective survey, treatment with
      testosterone and/or GH was associated with favorable effects in men and women
      across a wide age range.

PMID- 21197339
TI  - Anxiety and mood disorder in young males with mitral valve prolapse.
AB  - OBJECTIVE: This study explored the prevalence of panic disorder and other
      psychiatric disorders in young Han Chinese males with mitral valve prolapse
      (MVP). With the factors of age, sex, and ethnicity controlled, the specific role
      of MVP in panic disorder was analyzed. METHODS: Subjects with chest pain aged
      between 18 and 25 years were assessed with the echocardiograph for MVP and the
      Chinese version of the Mini-International Neuropsychiatric Interview for panic
      disorder (n = 39). RESULTS: Of the 39 participants, 35.9% met the diagnosis of
      anxiety disorder, 46.2% met at least one criterion of anxiety disorder, and 23.1%
      met the diagnostic criteria of major depressive disorder. There was no
      statistically significant difference in the prevalence of panic disorder between
      one of the (8.3%) MVP patients, and two (7.4%) control participants. CONCLUSIONS:
      There is a high prevalence of psychiatric disorder, including anxiety disorder
      and major depressive disorder, in those who report pain symptoms, so that
      diagnosis and treatment of these patients is of great importance. In addition,
      individuals with MVP did not have an increased risk for panic disorder. Whether
      MVP may be a modifier or mediating factor for panic disorder needs to be further
      assessed in a larger scale study.

PMID- 21197340
TI  - A 70-year-old male with peripheral neuropathy, ataxia and antigliadin antibodies
      shows improvement in neuropathy, but not ataxia, after intravenous immunoglobulin
      and gluten-free diet.
AB  - This is a case of a 70-year-old man with severe peripheral neuropathy, type 2
      diabetes and progressively worsening cerebellar ataxia. He was found to have
      circulating antigliadin and antireticulin antibodies compatible with celiac
      disease in the absence of intestinal pathology. The peripheral neuropathy
      improved with a gluten-free diet, antioxidants and intravenous immunoglobulin,
      whereas the ataxia did not. This case illustrates the need to test for celiac
      disease in patients with idiopathic ataxia and peripheral neuropathy and the need
      for alternative therapies for ataxia.

PMID- 21197341
TI  - Measuring health outcomes of a multidisciplinary care approach in individuals
      with chronic environmental conditions using an abbreviated symptoms
      questionnaire.
AB  - The Nova Scotia Environmental Health Centre is a treatment facility for
      individuals with chronic environmental conditions such as multiple chemical
      sensitivity, chronic fatigue syndrome, fibromyalgia, chronic respiratory
      conditions and in some cases chronic pain. The premise of care is to provide a
      patient-centred multidisciplinary care approach leading to self-management
      strategies. In order to measure the outcome of the treatment in these complex
      problems, with overlapping diagnoses, symptoms in many body systems and suspected
      environmental triggers, a detailed symptoms questionnaire was developed
      specifically for this patient population and validated. Results from a pilot
      study in which an abbreviated symptoms questionnaire based on the top reported
      symptoms captured in previous research was used to measure the efficacy of a
      multidisciplinary care approach in individuals with multiple chemical sensitivity
      are presented in this paper. The purpose of this study was to examine the extent,
      type and patterns of changes over time in the top reported symptoms with
      treatment measured using the abbreviated symptoms questionnaire. A total of 183
      active and 109 discharged patients participated in the study where the health
      status was measured at different time periods of follow up since the commencement
      of treatment at the Centre. The findings from this study were successful in
      generating an initial picture of the nature and type of changes in these
      symptoms. For instance, symptoms such as difficulty concentrating, sinus
      conditions and tiredness showed early improvement, within the first 6 months of
      being in treatment, while others, such as fatigue, hoarseness or loss of voice,
      took longer while others showed inconsistent changes warranting further enquiry.
      A controlled longitudinal study is planned to confirm the findings of the pilot
      study.

PMID- 21197342
TI  - Age- and sex-related regional compressive strength characteristics of human
      lumbar vertebrae in osteoporosis.
AB  - OBJECTIVE: To obtain the compressive load bearing and energy absorption capacity
      of lumbar vertebrae of osteoporotic elderly for the everyday medical praxis in
      terms of the simple diagnostic data, like computed tomography (CT), densitometry,
      age, and sex. METHODS: Compressive test of 54 osteoporotic cadaver vertebrae L1
      and L2, 16 males and 38 females (age range 43-93, mean age 71.6 +/- 13.3 years,
      mean bone mineral density (BMD) 0.377 +/- 0.089 g/cm(2), mean T-score -5.57 +/-
      0.79, Z-score -4.05 +/- 0.77) was investigated. Based on the load-displacement
      diagrams and the measured geometrical parameters of vertebral bodies,
      proportional, ultimate and yield stresses and strains, Young's modulus, ductility
      and energy absorption capacity were determined. Three vertebral regions were
      distinguished: superior, central and inferior regions, but certain parameters
      were calculated for the upper/ lower intermediate layers, as well. Cross
      sectional areas, and certain bone tissue parameters were determined by image
      analysis of CT pictures of vertebrae. Sex- and age-related decline functions and
      trends of strength characteristics were determined. RESULTS: Size-corrected
      failure load was 15%-25% smaller in women, proportional and ultimate stresses
      were about 30%-35% smaller for women in any region, and 20%-25% higher in central
      regions for both sexes. Young's moduli were about 30% smaller in women in any
      region, and 20%-25% smaller in the central region for both sexes. Small strains
      were higher in males, large strains were higher in females, namely, proportional
      strains were about 25% larger in men, yield and ultimate strains were quasi equal
      for sexes, break strains were 10% higher in women. Ultimate energy absorption
      capacity was 10%-20% higher in men; the final ductile energy absorption capacity
      was quasi equal for sexes in all levels. Age-dependence was stronger for men,
      mainly in central regions (ultimate load, male: r = -0.66, p < 0.01, female: r = 
      0.52, p < 0.005; ultimate stress, male: r = -0.69, p < 0.01, female: r = -0.50, p
      < 0.005; Young's modulus, male: r = -0.55, p < 0.05, female: r = -0.52, p <
      0.005, ultimate stiffness, male: r = -0.58, p < 0.05, female: r = -0.35, p <
      0.03, central ultimate absorbed energy density, male: r = -0.59, p < 0.015,
      female: r = -0.29, p < 0.08). CONCLUSIONS: For the strongly osteoporotic
      population (BMD < 0.4 g/cm(2), T-score < -4) the statical variables (loads,
      stresses) showed significant correlation; mixed variables (stiffness, Young's
      modulus, energy) showed moderate correlation; kinematical variables
      (displacements, strains) showed no correlation with age. The strong correlation
      of men between BMD and aging (r = -0.82, p < 0.001) and betwen BMD and strength
      parameters (r = 0.8-0.9, p < 0.001) indicated linear trends in age-related
      strength loss for men; however, the moderate correlation of women between BMD and
      aging (r = -0.47, p < 0.005) and between BMD and strength parameters (r = 0.4
      0.5, p < 0.005) suggested the need of nonlinear (quadratic) approximation that
      provided the better fit in age-related strength functions of females modelling
      postmenopausal disproportionalities.

PMID- 21197343
TI  - Sensory impairment in hip-fracture patients 65 years or older and effects of
      hearing/vision interventions on fall frequency.
AB  - AIM: Examine the effect of nursing interventions to improve vision and hearing,
      systematic assessment, and referral to sensory specialists on falling. METHODS:
      Controlled intervention trial targeting hip fracture patients, 65 years and
      older, living at home and having problems seeing/reading regular print (VI) or
      hearing normal speech (HI). Intervention group = 200, control group = 131. The
      InterRAI-AcuteCare (RAI-AC) and the Combined-Serious-Sensory-Impairment interview
      guide (KAS-Screen) were used. Follow-up telephone calls were done every third
      month for one year. RESULTS: Mean age was 84.2 years, 79.8% were female, and
      76.7% lived alone. HI was detected in 80.7% and VI in 59.8%. Falling was more
      frequent among the intervention group (P = 0.003) and they also more often moved
      to a nursing home (P < 0.001) and were dependent walking up stairs (P = 0.003).
      CONCLUSIONS: This study could not document the effect of intervention on falling,
      possibly because of different base line characteristics (more females, P = 0.018,
      and more living alone P = 0.011 in the intervention group), differences in
      nursing care between subjects, and different risk factors. Interventions to
      improve sensory function remain important in rehabilitation, but have to be
      studied further.

PMID- 21197344
TI  - Long-term sick-leavers with fibromyalgia: Comparing their multidisciplinarily
      assessed characteristics with those of others with chronic pain conditions and
      depression.
AB  - OBJECTIVE: The aim was to gain knowledge of fibromyalgia (FM) patients on long
      term sick leave and with particular difficulties in resuming work, and to compare
      them with patients with myalgia, back or joint diagnoses, and depression.
      METHODS: Patients were identified by and referred from social insurance offices
      and were multidisciplinarily examined by three board-certified specialists in
      psychiatry, orthopedic surgery and rehabilitation medicine. Ninety-two women were
      diagnosed with FM only. Three female comparison groups were chosen: depression,
      back/joint diagnoses, and myalgia. RESULTS AND CONCLUSIONS: Ceaseless pain was
      reported by 73% of FM patients, 54% of back/joint diagnoses patients, 43% of
      myalgia patients, and 35% of depression patients. The distribution of pain (>50%)
      in FM patients was to almost all regions of the body, and in depression patients
      to the lower dorsal neck, upper shoulders and lumbosacral back but not in the
      anterior body. Reduced sleep was more evident in FM patients. FM patients did not
      meet more criteria for personality disorder than patients with the other somatic
      pain conditions. The most common dimension of "personality traits" of somatic
      pain conditions was the "obsessive compulsive" but at a level clearly below that
      indicating a personality disorder. More FM patients experienced disabilities, the
      most common being in the mobility and domestic-life areas.

PMID- 21197345
TI  - Maximally efficient two-stage screening: Determining intellectual disability in
      Taiwanese military conscripts.
AB  - OBJECTIVE: The purpose of this study was to apply a two-stage screening method
      for the large-scale intelligence screening of military conscripts. METHODS: We
      collected 99 conscripted soldiers whose educational levels were senior high
      school level or lower to be the participants. Every participant was required to
      take the Wisconsin Card Sorting Test (WCST) and the Wechsler Adult Intelligence
      Scale-Revised (WAIS-R) assessments. RESULTS: Logistic regression analysis showed
      the conceptual level responses (CLR) index of the WCST was the most significant
      index for determining intellectual disability (ID; FIQ <= 84). We used the
      receiver operating characteristic curve to determine the optimum cut-off point of
      CLR. The optimum one cut-off point of CLR was 66; the two cut-off points were 49
      and 66. Comparing the two-stage window screening with the two-stage positive
      screening, the area under the curve and the positive predictive value increased.
      Moreover, the cost of the two-stage window screening decreased by 59%.
      CONCLUSION: The two-stage window screening is more accurate and economical than
      the two-stage positive screening. Our results provide an example for the use of
      two-stage screening and the possibility of the WCST to replace WAIS-R in large
      scale screenings for ID in the future.

PMID- 21197346
TI  - Nurse stress at two different organizational settings in Alexandria.
AB  - OBJECTIVE: The objective of the study was to explore the difference in stress
      levels among nurses working at two different health care organizations and the
      determinants of nurse stress within each organization. Job stress is defined as
      the harmful emotional and physical reactions resulting from the interactions
      between the worker and her/his work environment where the demands of the job
      exceed the worker's capabilities and resources. METHODOLOGY: A convenient sample
      of nurses in two hospitals in Alexandria; Shark Al Madina (n = 120) and Karmouz
      (n = 170) hospitals. All nurses present at the time of the study were approached
      to be included in the study. The response rate for Shark Al Madina hospital was
      94% and for Karmouz hospital, 71%. Data collection took place using a nurse
      stress questionnaire previously developed and tested for validity and reliability
      to measure stress in clinical nursing practice. The 5% level of significance was
      used throughout the statistical analysis for all relevant tests. RESULTS: The
      highest mean stress scores were the same for both hospitals. The dimension of
      coping with new situations was 2.7 +/- 0.6 at Shark Al Madina hospital and was
      2.5 +/- 0.7 at Karmouz hospital while the dimension of job security was 2.7 +/-
      0.6 and 2.5 +/- 0.7 at Shark Al Madina and Karmouz hospitals, respectively.
      Stepwise multiple regression for Shark Al Madina hospital model revealed workload
      (beta = 1.38), security (beta = 5.04), and shortage of support staff (beta =
      3.39). For the Karmouz hospital model, stepwise multiple regression revealed
      security (beta = 4.78) and shortage of resources (beta = 3.66). CONCLUSION:
      Stressors among nurses appear to be the same despite the differences in
      organizational or hierarchical structure where they work or the type of consumer
      they serve. It is important to reduce occupational stress in nurses and to
      strengthen their coping resources to prevent nurse burnout. This could be
      achieved with job redesign, modification of shift work systems, and by offering
      occupational health education as well as assurance regarding job security
      especially during the global financial crisis.

PMID- 21197347
TI  - A controlled study of the effect of a mindfulness-based stress reduction
      technique in women with multiple chemical sensitivity, chronic fatigue syndrome,
      and fibromyalgia.
AB  - BACKGROUND: The objective of this study was to examine the effect of a
      mindfulness-based stress reduction (MBSR) program on women diagnosed with
      conditions such as multiple chemical sensitivity (MCS), chronic fatigue syndrome
      (CFS), and fibromyalgia (FM). METHODS: The intervention group underwent a 10-week
      MBSR program. Symptoms Checklist Inventory (SCL-90R) was used as outcome measure
      and was administered before the start of the program (pre-), immediately upon
      completion (post-) and at three-month follow-up. Women on the wait list to
      receive treatment at the Nova Scotia Environmental Health Centre were used as
      control subjects for the study. RESULTS: A total of 50 participants in the
      intervention group and 26 in the wait-list controls group were recruited for this
      study. Global scores in the intervention group reached statistical significance
      pre-post (<0.0001) and at pre-follow-up (<0.0001) while the global scores in the
      control group remained the same. Five of nine and eight of nine subscales of the
      SCL-90R showed improvement of statistical significance in MBSR group following
      treatment and at three-month follow-up. CONCLUSIONS: The study showed the
      importance of complementary interventions such as MBSR techniques in the
      reduction of psychological distress in women with chronic conditions.

PMID- 21197348
TI  - Multidisciplinary program for stress-related disease in primary health care.
AB  - OBJECTIVE: To describe a multidisciplinary program, given by an occupational
      therapist and a physiotherapist, for patients with stress-related disease in
      primary health care and to measure the effect of this program in terms of self
      perceived health, degree of burnout, physical activity, symptoms, recreational
      activities, and psychological and physical well-being. METHOD: Retrospective
      study. RESULTS: At measures after three months, the thirteen patients included in
      this study had improved in self-estimated health, measured with EuroQol-5D Visual
      Analogue Scale (p = 0.000), and in degree of burnout, measured with the Shirom
      Melamed Burnout Questionnaire (p = 0.001). There was also a decrease in presence
      of headache, in physical activity and in satisfaction with leisure time, although
      not statistically significant. After six months, the improvements remained for
      all measures except physical activity. The patients were also satisfied with the
      program to a high degree, measured with Client Satisfaction Questionnaire (median
      3.7). CONCLUSION: This descriptive study shows that a stress-management program,
      provided by a team including an occupational therapist and a physiotherapist in
      primary health care, is both feasible and effective in terms of self-estimated
      health, degree of burnout, and patient satisfaction.

PMID- 21197349
TI  - Integrated care and optimal management of pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) may occur as an idiopathic process or as a
      component of a variety of diseases, including connective tissue diseases,
      congenital heart disease, and exposure to appetite suppressants or infectious
      agents such as HIV. Untreated, it is a potentially devastating disease; however,
      diagnosis can be difficult due to the non-specific nature of symptoms during the
      early stages, and the fact that patients often present to a range of different
      medical specialties. The past decade has seen remarkable improvements in our
      understanding of the pathology associated with the condition and the development
      of PAH-specific therapies with the ability to alter the natural history of the
      disease. This article reviews the evidence for screening and diagnosis of
      susceptible patient groups and discusses treatment selection and recommendations
      based on data available from randomized controlled trials. In addition, due to
      the complexity of the diagnostic evaluation required and the treatment options
      available, this review mandates for a multidisciplinary approach to the
      management of PAH. We discuss the roles and organizational structure of a
      specialized PAH center in Perth, Western Australia to highlight these issues.

PMID- 21197350
TI  - "If we only got a chance." Barriers to and possibilities for a more health
      promoting health service.
AB  - AIM: With the overall objective to develop future strategies for a more health
      promoting health service in Sweden, the aim of this paper was to describe how
      health personnel view barriers and possibilities for having a health-promoting
      role in practice. MATERIALS AND METHODS: Seven focus group discussions were
      carried out with a total of 34 informants from both hospital and primary health
      care settings in Sweden. The informants represented seven professional groups;
      counselors, occupational therapists, assistant nurses, midwives, nurses,
      physicians, and physiotherapists. The data were analyzed using qualitative
      content analysis. RESULTS: The analysis resulted in one major theme "If we only
      got a chance". The theme captures the health professionals' positive view about,
      and their willingness to, develop a health-promoting and/or preventive role,
      while at the same time feeling limited by existing values, structures, and
      resources. The four categories, "organizational commitment to a paradigm shift",
      "recognition of staff as health-promoting instruments", "a balance between
      resources and tasks", and "freedom of action" capture what is needed for
      implementing and increasing health promotion and preventive efforts in the health
      services. CONCLUSIONS: The study indicates that an organizational setting that
      support health promotion is still to be developed. There is a need for a more
      explicit leadership with a clear direction towards the goal of "a more health
      promoting health service" and with enough resources for achieving this goal.

PMID- 21197351
TI  - Home care patients in four Nordic capitals - predictors of nursing home admission
      during one-year followup.
AB  - The aim was to predict nursing home admission (NHA) for home care patients after
      a 12-month follow-up study. This Nordic study is derived from the aged in home
      care (AdHOC) project conducted in 2001-2003 with patients at 11 sites in Europe.
      The participants in the cohort study were randomly selected individuals, aged 65
      years or older, receiving homecare in Oslo, Stockholm, Copenhagen, and Reykjavik.
      The Resident Assessment Instrument for Home Care (version 2.0) was used.
      Epidemiological and medical characteristics of patients and service utilization
      were recorded for 1508 home care patients (participation rate 74%). In this
      sample 75% were female. The mean age was 82.1 (6.9) years for men and 84.0 (6.6)
      for women. The most consistent predictor of NHA was receiving skilled nursing
      procedures at baseline (help with medication and injections, administration or
      help with oxygen, intravenous, catheter and stoma care, wounds and skin care)
      (adjusted odds ratio = 3.7, 95% confidence interval: 1.7-7.8; P < 0.001). In this
      Nordic material, stronger emphasizing on higher qualified nurses in a home care
      setting could prevent or delay NHA.

PMID- 21197352
TI  - Weightbath hydrotraction treatment: application, biomechanics, and clinical
      effects.
AB  - BACKGROUND AND PURPOSE: Weightbath hydrotraction treatment (WHT) is a simple
      noninvasive effective method of hydro- or balneotherapy to stretch the spine or
      lower limbs, applied successfully in hospitals and health resort sanitaria in
      Hungary for more than fifty years. This study aims to introduce WHT with its
      biomechanical and clinical effects. History, development, equipment, modes of
      application, biomechanics, spinal traction forces and elongations, indications
      and contraindications of WHT are precented. SUBJECTS AND METHODS: The calculation
      of traction forces acting along the spinal column during the treatment is
      described together with the mode of suspension and the position of extra weight
      loads applied. The biomechanics of the treatment are completed by in vivo
      measured elongations of lumbar segments using a special underwater ultrasound
      measuring method. The clinical effects, indications, and contraindications of the
      treatment are also presented. RESULTS: In the underwater cervical suspension of a
      human body, approximately 25 N stretching load occurs in the cervical spine, and
      about 11 N occurs in the lumbar spine. By applying extra weights, the above
      tensile forces along the spinal column can be increased. Thus, the traction
      effect can be controlled by applying such loads during the treatment. Elongations
      of segments L3-L4, L4-L5, and L5-S1 were measured during the usual WHT of
      patients suspended cervically in water for 20 minutes, loaded by 20-20 N lead
      weights on the ankles. The mean initial elastic elongations of spinal segments
      were about 0.8 mm for patients aged under 40 years, 0.5 mm between 40-60 years,
      and 0.2 mm for patients over 60 years. The mean final viscoelastic elongations
      were 1.5 mm, 1.2 mm, and 0.6 mm for the same age classes, respectively. No
      significant difference was found between the sexes regarding age-dependence in
      tension. WHT for discopathy showed significant improvement of clinical
      parameters, which was still evident three months later, as demonstrated by using
      a controlled pilot study. CONCLUSION AND DISCUSSION: WHT effectively mitigates
      pain, enhances joint flexibility, and improves the quality of life of patients.
      The WHT equipment is easy to install and the treatment technique is simple. The
      authors are the first to determine the biomechanical effects of WHT using an in
      vivo-measuring method and biomechanical calculations; and verifying the
      beneficial clinical effects by a controlled pilot study. Approximate values of
      tensile forces occurring along different points of the spinal column have been
      calculated, depending on the mode of the suspension, and the value and position
      of the applied extra weight loads. Time-related viscoelastic elongations of
      lumbar segments and discs have been measured in vivo, in terms of sex, age, body
      weight and height and the position of the segment. Several clinical parameters
      were analyzed by a controlled pilot study to verify the beneficial effects of WHT
      for cervical and lumbar discopathy. Based on these results, advice can be given
      to therapists to obtain the optimal traction effects of the treatment.

PMID- 21197353
TI  - Personality of mothers of substance-dependent patients.
AB  - Drug addicts often come from dysfunctional families. The prevailing view in the
      literature is that mothers of drug-dependent patients can be characterized by
      strong emotional bonds and overprotection. Studies suggest that maternal
      rejection could be a major risk factor of developing drug addiction. This work is
      a continuation of our previous study of childhood parenting experiences of
      substance-dependent patients. The aims were to compare the personality profile of
      mothers of substance-dependent patients and that of mothers of matched control
      subjects; and to examine the relation between the personality of mothers of
      addicts, and severity of their offspring's addiction. The study group consisted
      of 20 mothers of substance-dependent patients and a control group of 35 mothers
      of non-dependent subjects; mothers of both groups were age matched. Patients were
      diagnosed according to DSM IV criteria. Personalities of mothers of both groups
      were assessed using the Minnesota Multiphasic Personality Inventory (MMPI).
      Substance-dependent patients (sons) were administered the Addiction Severity
      Index (ASI). The mean scores of the MMPI Scales were higher for mothers of
      dependent patients compared to mothers of non-dependent subjects. Scores on the
      depression, hysteria and paranoia scales were significantly higher for mothers of
      patients (P = 0.03, 0.02, and 0.03, respectively). There was a significant
      positive correlation between scores of hysteria, and psychopathic deviance and
      the ASI (P = 0.03 and 0.01, respectively). There were significant negative
      correlations between scores of social introversion and the ASI drug/alcohol use
      status (P = 0.007), and family history dimensions (P = 0.003). Mothers of
      substance-dependent patients showed disturbances in aspects of personalities that
      might be related to initiation of perpetuation of substance dependence.

PMID- 21197354
TI  - "Integrated knowledge translation" for globally oriented public health
      practitioners and scientists: Framing together a sustainable transfrontier
      knowledge translation vision.
AB  - The development of a dynamic leadership coalition between practitioners and
      researchers/scientists - which is known in Canada as integrated knowledge
      translation (KT) - can play a major role in bridging the know-do gap in the
      health care and public health sectors. In public health, and especially in
      globally oriented public health, integrated KT is a dynamic, interactive
      (collaborative), and nonlinear phenomenon that goes beyond a reductionist vision
      of knowledge translation, to attain inter-, multi-, and even transdisciplinary
      status. Intimately embedded in its socioenvironmental context and closely
      connected with the complex interventions of multiple actors, the nonlinear
      process of integrated KT is based on a double principle: (1) the principle of
      transcendence of frontiers (sectorial, disciplinary, geographic, cultural, and
      cognitive), and (2) the principle of integration of knowledge beyond these
      frontiers. However, even though many authors agree on the overriding importance
      of integrated KT, there is as yet little understanding of the causal framework of
      integrated KT. Here, one can ask two general questions. Firstly, what
      "determines" integrated KT? Secondly, even if one wanted to apply a
      "transfrontier knowledge translation" vision, how should one go about doing so?
      For example, what would be the nature and qualities of a representative research
      program that applied a "transfrontier collaboration" approach? This paper focuses
      on the determinants of integrated KT within the burgeoning field of knowledge
      translation research (KT research). The paper is based on the results of a
      concurrent mixed method design which dealt with the complexity of building and
      sustaining effective coalitions and partnerships in the health care and public
      health sectors. The aims of this paper are: (1) to present an "integrated KT"
      conceptual framework which is global-context-sensitive, and (2) to promote the
      incorporation of a new "transfrontier knowledge translation" approach/vision
      designed primary for globally oriented public health researchers and health
      scientists.

PMID- 21197355
TI  - Relationship between nursing workloads and patient safety incidents.
AB  - OBJECTIVE: To evaluate the relationship between nursing workloads and patient
      safety incidents in inpatient wards of a general hospital. METHODS: A
      retrospective data analysis was conducted involving the internal medicine wards
      in a teaching hospital in Japan between July 1st and December 31st, 2006. To
      assess associations between nursing workloads and patient safety incidents, we
      analyzed the following: the relationships between the level of patients'
      dependency and the number of incident reports; and the relationships between the
      presence of accidental falls and the presence of patients transferred from the
      intensive care unit to the wards. RESULTS: Fifty-five nurses worked on the wards
      (105 beds). The total number of incidents was 142 over the 184 days of this
      study. There was a positive trend between the number of incidents and the total
      patient dependency score. The presence of accidental falls in the wards was
      associated with the presence of transfers from the intensive care unit to the
      wards (odds ratio 3.14, 95% confidence interval: 1.48, 6.65). CONCLUSION: Greater
      nursing workloads may be related to the higher number of patient safety incidents
      in inpatient wards of hospitals.

PMID- 21197356
TI  - Two resource distribution strategies for dynamic mitigation of influenza
      pandemics.
AB  - As recently pointed out by the Institute of Medicine, the existing pandemic
      containment and mitigation models lack the dynamic decision support capabilities.
      We present two simulation-based optimization models for developing dynamic
      predictive resource distribution strategies for cross-regional pandemic
      outbreaks. In both models, the underlying simulation mimics the disease and
      population dynamics of the affected regions. The quantity-based optimization
      model generates a progressive allocation of limited quantities of mitigation
      resources, including vaccines, antiviral, administration capacities, and social
      distancing enforcement resources. The budget-based optimization model strives
      instead allocating a total resource budget. Both models seek to minimize the
      impact of ongoing outbreaks and the expected impact of potential outbreaks. The
      models incorporate measures of morbidity, mortality, and social distancing,
      translated into the societal and economic costs of lost productivity and medical
      expenses. The models were calibrated using historic pandemic data and implemented
      on a sample outbreak in Florida, with over four million inhabitants. The quantity
      based model was found to be inferior to the budget-based model, which was
      advantageous in its ability to balance the varying relative cost and
      effectiveness of individual resources. The models are intended to assist public
      health policy makers in developing effective distribution policies for mitigation
      of influenza pandemics.

PMID- 21197358
TI  - Clinicoradiological features of recurrent ischemic stroke: healthcare for
      poststroke patients.
AB  - OBJECTIVE: Little is known about recurrent risk profile of brain infarct (BI) in
      Japan. The study aimed to clarify clinicoradiological features of recurrent BI
      patients. METHODS: 374 consecutive BI patients (231 men and 143 women) were
      admitted to our department between 2007 and 2008. Recurrent BI was defined as a
      prior history of BI. Cardiovascular disease (CVD) risk profile, stroke mechanism
      subtypes and Bamford subtypes were compared between the first BI and the
      recurrent BI group. CVD risk factors, stroke subtypes of the first BI and
      preventative medication were analyzed in recurrent BI patients. RESULTS:
      Recurrent BI existed in 72 patients (40 men and 32 women). Age of the recurrent
      BI group was significantly older than the first BI group (P < 0.01). In
      comparison to the first BI group, the recurrent BI group had a high frequency of
      hypertension (P < 0.01) and CVD comorbidity (P < 0.05). Recurrent rates were
      increased significantly in cardioembolic patients as compared to the first BI
      patients (P < 0.05). Bamford BI subtypes did not differ between both groups. Mean
      recurrent interval (SD) was 3.1 (2.3) years. Approximately half the patients
      experienced recurrent BI less than 2 years after the first BI. Antiplatelet
      agents were used in 33 patients and warfarin was used in 12 patients as
      preventative medication. The remaining 27 patients had no prevention therapy by
      self-cessation. Nine warfarin users were controlled poorly. There were no
      significant correlations between the first and recurrent Bamford subtypes in
      recurrent BI patients. CONCLUSIONS: The present study indicated that the
      recurrent frequency of BI was 19.3%. Causative profile of recurrent BI suggested
      elderly age (>=65 years), hypertension, prior history of CVD, cardioembolism, 2
      years poststroke, insufficient treatment of warfarin and self-cessation of
      preventative medication. Thus, physicians should pay more attention to these
      aspects for prophylaxis of recurrent BI in poststroke patients.

PMID- 21197357
TI  - Uses and benefits of omega-3 ethyl esters in patients with cardiovascular
      disease.
AB  - Much evidence on the favorable effects of omega-3 ethyl esters on cardiovascular
      morbidity and mortality has been obtained in studies performed in healthy
      subjects and in different clinical settings. Here the clinical effects of omega-3
      ethyl ester administration in patients with previous myocardial infarction or
      heart failure are reviewed, together with a discussion of underlying mechanisms
      of action. The pharmacokinetic and pharmacodynamic properties of omega-3 ethyl
      esters, as well as evidence concerning their safety and tolerability, are also
      reported.

PMID- 21197359
TI  - Do pressure ulcer risk assessment scales improve clinical practice?
AB  - Standardized assessment instruments are deemed important for estimating pressure
      ulcer risk. Today, more than 40 so-called pressure ulcer risk assessment scales
      are available but still there is an ongoing debate about their usefulness. From a
      measurement point of view pressure ulcer (PU) risk assessment scales have serious
      limitations. Empirical evidence supporting the validity of PU risk assessment
      scale scores is weak and obtained scores contain varying amounts of measurement
      error. The concept of pressure ulcer risk is strongly related to the general
      health status and severity of illness. A clinical impact due do the application
      of these scales could also not be demonstrated. It is questionable whether
      completion of standardized pressure ulcer risk scales in clinical practice is
      really needed.

PMID- 21197361
TI  - Development of a Bayesian model to estimate health care outcomes in the severely
      wounded.
AB  - BACKGROUND: Graphical probabilistic models have the ability to provide insights
      as to how clinical factors are conditionally related. These models can be used to
      help us understand factors influencing health care outcomes and resource
      utilization, and to estimate morbidity and clinical outcomes in trauma patient
      populations. STUDY DESIGN: Thirty-two combat casualties with severe extremity
      injuries enrolled in a prospective observational study were analyzed using step
      wise machine-learned Bayesian belief network (BBN) and step-wise logistic
      regression (LR). Models were evaluated using 10-fold cross-validation to
      calculate area-under-the-curve (AUC) from receiver operating characteristics
      (ROC) curves. RESULTS: Our BBN showed important associations between various
      factors in our data set that could not be developed using standard regression
      methods. Cross-validated ROC curve analysis showed that our BBN model was a
      robust representation of our data domain and that LR models trained on these
      findings were also robust: hospital-acquired infection (AUC: LR, 0.81; BBN,
      0.79), intensive care unit length of stay (AUC: LR, 0.97; BBN, 0.81), and wound
      healing (AUC: LR, 0.91; BBN, 0.72) showed strong AUC. CONCLUSIONS: A BBN model
      can effectively represent clinical outcomes and biomarkers in patients
      hospitalized after severe wounding, and is confirmed by 10-fold cross-validation
      and further confirmed through logistic regression modeling. The method warrants
      further development and independent validation in other, more diverse patient
      populations.

PMID- 21197360
TI  - Multidisciplinary management of type 2 diabetes in children and adolescents.
AB  - Although once considered a disease of adults, the prevalence of type 2 diabetes
      in youth is increasing at a significant rate. Similar to adults, youth with type
      2 diabetes are at increased risk for developing hypertension, lipid
      abnormalities, renal disease, and other diabetes-related complications. However,
      children and adolescents with type 2 diabetes also face many unique management
      challenges that are different from adults with type 2 diabetes or children with
      type 1 diabetes. To deliver safe, effective, high-quality, cost-effective health
      care to adolescents with type 2 diabetes, reorganization and redesign of health
      care systems are needed. Multidisciplinary health care teams, which allow
      individuals with specialized training to maximally utilize their skills within an
      organized diabetes treatment team, may increase efficiency and effectiveness and
      may improve outcomes in children with type 2 diabetes. This review article
      provides a brief review of type 2 diabetes in children and adolescents, provides
      an overview of multidisciplinary health care teams, and discusses the role of
      multidisciplinary health care management in youth with type 2 diabetes.

PMID- 21197363
TI  - Allied health assistants and what they do: A systematic review of the literature.
AB  - OBJECTIVE: Allied health assistants (AHAs) are an emerging group in allied health
      practice with the potential to improve quality of care and safety of patients.
      This systematic review summarizes the evidence regarding the roles and
      responsibilities of AHAs and describes the benefits and barriers to utilizing
      AHAs in current health care settings. METHODS: A systematic process of literature
      searching was undertaken. A search strategy which included a range of electronic
      databases was searched using key terms. Studies which examined the roles and
      responsibilities of AHAs (across all allied health disciplines) were included in
      the review. Only publications written in the English language were considered,
      with no restriction on publication date. Two reviewers independently assessed
      eligibility of the articles. Data extraction was performed by the same reviewers.
      A narrative summary of findings was presented. RESULTS: Of the initial 415
      papers, 10 studies were included in the review. The majority of papers reported
      roles performed by general health care assistants or rehabilitation assistants
      who work in multiple settings or are not specifically affiliated to a health
      discipline. All current AHAs duties have elements of direct patient care and
      indirect support via clerical and administrative or housekeeping tasks. Benefits
      from the introduction of the AHA role in health care include improved clinical
      outcomes, increased patient satisfaction, higher-level services, and more "free"
      time for allied health professionals to concentrate on patients with complex
      needs. Barriers to the use of AHAs are related to blurred role boundaries, which
      raises issues associated with professional status and security. CONCLUSIONS:
      There is consensus in the literature that AHAs make a valuable contribution to
      allied health care. Whilst there are clear advantages associated with the use of
      AHAs to support allied health service delivery, ongoing barriers to their
      effective use persist.

PMID- 21197362
TI  - Music and medicine.
AB  - Healing sounds have always been considered in the past an important aid in
      medical practice, and nowadays, medicine has confirmed the efficacy of music
      therapy in many diseases. The aim of this study is to assess the curative power
      of music, in the frame of the current clinical relationship.

PMID- 21197364
TI  - Effect on work ability after team evaluation of functioning regarding pain, self
      rated disability, and work ability assessment.
AB  - To evaluate the effect of a 1-2 week multiprofessional team assessment, without a
      real rehabilitation effort, 60 patients suffering from long-standing pain and on
      long-lasting time on sick leave were studied. A questionnaire concerning their
      daily activities, quality of life, pain intensity, sick-leave level, and their
      work state was filled out by all patients before starting the assessment and at a
      1-year follow-up. The results from the assessment period and the
      multiprofessional team decision of the patient's working ability were compared
      with the actual working rate after 1 year. The follow-up showed a significant
      reduction of sick leave and a higher level of activity (P < 0.001). One year
      after the initial evaluation, 40% showed a reduction in sickness benefit level
      and 12% resumed full-time work. However, the team evaluation of the patient's
      work ability did not correlate to predict the actual outcome. The patient's pain
      intensity, life satisfaction, gender, age, ethnic background, and time absent
      from work before the start of the evaluation showed no correlation to reduction
      on time on sickness benefit level. These parameters could not be used as
      predictors in this study.

PMID- 21197365
TI  - Comparison between the Beck Depression Inventory and psychiatric evaluation of
      distress in patients on long-term sick leave due to chronic musculoskeletal pain.
AB  - BACKGROUND: Chronic musculoskeletal pain (CMP) is associated with psychological
      distress and long-term disability. Underlying diagnoses causing long-term
      sickness absence due to CMP have not been explored enough. In a somatic health
      care setting, it is important to identify mental health comorbidity to facilitate
      the selection of appropriate treatment. The objectives of this study were to
      compare the scores of depressed mood obtained on the Beck Depression Inventory
      (BDI) with the diagnosis of depression made by a psychiatrist, and to study the
      prevalence of undiagnosed mental health comorbidity in these patients. METHODS
      AND PATIENTS: 83 consecutive patients on sick leave (mean duration 21 months) due
      to CMP who had been referred by the Social Insurance Office to an orthopedist and
      a psychiatrist for assessment of the patient's diagnoses and capacity to work.
      The mean age was 45 (23-61) years, 58% were women and 52% were immigrants. The
      accuracy of measurements was calculated using the Diagnostic Statistical Manual
      of Mental Disorders IV as the Gold standard. RESULTS: Psychiatric illness was
      diagnosed in 87% of the patients. The diagnosis was depression in 56%, other
      psychiatric illnesses in 31%, whereas 13% were mentally healthy. Of all the
      patients, only 10% had a previous psychiatric diagnosis. The median value of the
      BDI score was 26 points in depressed patients, whereas it was 23 in patients with
      other psychiatric diagnoses. The sensitivity of the BDI to detect depression was
      87.5%. We found good agreement between the BDI score and a diagnosis of
      depression. CONCLUSION: Undiagnosed psychiatric disorders were commonly seen in
      patients with CMP. The high sensitivity of the BDI scores enables the screening
      of mental health comorbidity in patients with a somatic dysfunction. The test is
      a useful tool for detecting distress in patients who are on long-term sick leave
      due to CMP and who need additional treatment.

PMID- 21197366
TI  - Reliability of a seminar grading rubric in a grand rounds course.
AB  - PURPOSE: Formal presentations are a common requirement for students in health
      professional programs, and evaluations are often viewed as subjective. To date,
      literature describing the reliability or validity of seminar grading rubrics is
      lacking. The objectives of this study were to characterize inter-rater agreement
      and internal consistency of a grading rubric used in a grand rounds seminar
      course. METHODS: Retrospective study of 252 student presentations given from fall
      2007 to fall 2008. Data including student and faculty demographics, overall
      content score, overall communication scores, subcomponents of content and
      communication, and total presentation scores were collected. Statistical analyses
      were performed using SPSS, 16.0. RESULTS: The rubric demonstrated internal
      consistency (Cronbach's alpha = 0.826). Mean grade difference between faculty
      graders was 4.54 percentage points (SD = 3.614), with <= 10-point difference for
      92.5% of faculty evaluations. Student self evaluations correlated with faculty
      scores for content, communication, and overall presentation (r = 0.513, r =
      0.455, and r = 0.539; P < 0.001 for all respectively). When comparing mean
      faculty scores to student's self-evaluations between quintiles, students with
      lower faculty evaluations overestimated their performance, and those with high
      faculty evaluations underestimated their performance (P < 0.001). CONCLUSION: The
      seminar evaluation rubric demonstrated inter-rater agreement and internal
      consistency.

PMID- 21197367
TI  - Integrated management strategies for chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) remains the fourth leading cause of
      death, is associated with significant morbidity and places a substantial time and
      cost burden on the health care system. Unfortunately, treatment for COPD remains
      underutilized and continues to focus on the acute care of complications. The
      chronic care model (CCM) shifts this focus from the acute management of symptoms
      and complications to the prevention and optimal management of the chronic
      disease. This model utilizes resources from the community and the health care
      system and emphasizes self-management, provides comprehensive clinic support, and
      implements evidence-based guidelines and technology into clinical practice to
      ensure delivery of the highest quality of care. The goal of this review is to use
      a case-based approach to provide practical information about how integrated care
      using the CCM can be applied to the clinical care of a complex patient with COPD,
      shifting the management goals for COPD from reactive to proactive and ultimately
      improving outcomes.

PMID- 21197368
TI  - Health care - an everlasting challenge in temporal and spatial domains.
AB  - Health care is an everlasting challenge that requires effort at all levels, from
      national and organizational to individual domains, over a long-term period. This
      article reviews the historical development of health care-related issues
      worldwide and accentuates the necessity of health care in the current era.
      Through investigating the historical background in both the occidental and the
      oriental worlds and the latest achievements from academic and industrial
      endeavors, many lessons can be learnt, and as a result, an integrative strategy
      is proposed to meet today's pressing needs. A government-funded project,
      "Challenge to 100 years of age", which involved more than 600 residents in west
      Aizu village, lasted over 15 years. After reviewing its outcomes, a metrology of
      health based upon the three-dimensional phase space, which integrates with social
      well-being, mental status, and physical condition for a lifelong span, is
      advocated as a measure of the holistic view of health state.

PMID- 21197369
TI  - Stochastic Approximation and Modern Model-based Designs for Dose-Finding Clinical
      Trials.
AB  - In 1951 Robbins and Monro published the seminal paper on stochastic approximation
      and made a specific reference to its application to the "estimation of a quantal
      using response, non-response data". Since the 1990s, statistical methodology for
      dose-finding studies has grown into an active area of research. The dose-finding
      problem is at its core a percentile estimation problem and is in line with what
      the Robbins-Monro method sets out to solve. In this light, it is quite surprising
      that the dose-finding literature has developed rather independently of the older
      stochastic approximation literature. The fact that stochastic approximation has
      seldom been used in actual clinical studies stands in stark contrast with its
      constant application in engineering and finance. In this article, I explore
      similarities and differences between the dose-finding and the stochastic
      approximation literatures. This review also sheds light on the present and future
      relevance of stochastic approximation to dose-finding clinical trials. Such
      connections will in turn steer dose-finding methodology on a rigorous course and
      extend its ability to handle increasingly complex clinical situations.

PMID- 21197370
TI  - Nicotine dependence.
AB  - PSYCHIATRISTS MUST BE CONCERNED with nicotine dependence (ND), because habitual
      smoking is so common among individuals with psychiatric disorders.(1) For
      example, approximately 90% of alcohol-dependent and opioid-dependent persons are
      also dependent on nicotine.(2,3) In addition, de Leon et al(4) found that
      approximately 80% of patients with schizophrenia are daily smokers. Given the
      long-term negative health consequences of daily smoking, psychiatrists must make
      treatment of ND in their patients a clinical focus.

PMID- 21197371
TI  - Symptom control and patient adherence to treatment: key goals in the treatment of
      psychosis.
AB  - A CLINICIAN'S KEY GOALS WHEN TREATING PSYCHOSIS ARE TO control disease symptoms
      and to ensure patient adherence to treatment. Efficacy as well as side-effect
      profile are, therefore, the major selection criteria when choosing an
      antipsychotic medication.

PMID- 21197372
TI  - Cognitive therapy for adjustment disorder in cancer patients.
AB  - A DIAGNOSIS OF CANCER INTERRUPTS THE LIFE OF A PATIENT AND HIS OR HER FAMILY.
      Cancer treatment often entails continued investigation and therapy that typically
      has side effects and offers the repeated warning to be vigilant. Cancer is often
      a life-threatening illness. The field of psycho-oncology is well established, and
      clinical oncologists often have a good awareness of the psychological challenges
      cancer poses to their patients. Despite the nature of the stressor, it is
      important to note that the majority of cancer patients do not meet diagnostic
      criteria for any emotional disorder.(1) Rather, their psychosocial stress can be
      conceptualized on a continuum (Figure 1) from normal adjustment to diagnosable
      mental disorders.(2).

PMID- 21197373
TI  - Beyond psychopharmacology for bipolar disorder: psychotherapeutic interventions
      for the patient and family.

PMID- 21197374
TI  - Specific treatment of residual fatigue in depressed patients.

PMID- 21197375
TI  - Borderline personality: a primary care context.
AB  - BORDERLINE PERSONALITY DISORDER (BPD) IS A COMPLEX AXIS II Phenomenon that is
      typically described in a psychological or psychiatric context. In this article,
      we translate the various aspects of BPD to the primary care setting. Previous
      work in this area has explored specific relationships between BPD and individual
      medical disorders or between BPD and general somatic symptoms, but the synthesis
      of these findings and their augmentation with cogent psychological theory is new
      to the field. Specifically, we highlight the prevalence rate of BPD in the
      primary care setting, the effects on healthcare utilization, the themes of
      somatic preoccupation and somatization disorder, several medical syndromes that
      illustrate the dynamics of the disorder in the medical setting, and the
      relationship of BPD to disability. We believe that the BPD concept needs to
      extend beyond its traditional psychological/psychiatric borders to include the
      subset of BPD patients with somatic symptoms who are seen in primary care
      settings.

PMID- 21197376
TI  - Computerized neurocognitive testing and its potential for modern psychiatry.
AB  - PSYCHIATRISTS SHOULD REVISIT THE ISSUE OF HOW TO ASSESS, OBJECTIVELY AND
      reliably, patients' cognitive status. Cognitive disorders, like ADHD (attention
      deficit/ hyperactivity disorder), and the various dementias are increasing in
      importance, and perhaps in number. The modern study of schizophrenia has focused
      on cognition as an outcome predictor; even the mood disorders can be associated,
      over time, with cognitive impairment. And with so many perfectly good drug
      alternatives in every therapeutic category, medications might be differentiated
      by virtue of their comparative effects on cognition. The best reason, however, is
      this: in clinical practice, cognitive assessment is either gross and insensitive
      or arduous and inordinately expensive.

PMID- 21197378
TI  - Psychotherapy with the mentally ill/ mentally retarded person.

PMID- 21197379
TI  - AUTOMATED RELIABLE LABELING OF THE CORTICAL SURFACE.
AB  - Accurate and reliable labeling of regions of interest (ROIs) within structural
      magnetic resonance images (MRIs) is an important step in group analysis. Group
      registration does not always yield accurate alignment of homologous regions. We
      present an approach that distinguishes itself from other algorithms by being
      concerned with a label which is of the highest fidelity, while leaving ambiguous
      regions unlabeled. Regions that are not deemed to be reliably labeled are not
      included in group statistics. We will present results showing that our method is
      an improvement over traditional multi-atlas voting schemes. We conclude with a
      pilot study of longitudinal trends of cortical thickness in normal aging.

PMID- 21197377
TI  - Genetics of major mood disorders.
AB  - The results presented in recent research suggest that nosology must be changed to
      reflect the genetic origins of the multiple disorders that are collectively
      described by the term bipolar disorder.

PMID- 21197380
TI  - ?
AB  - BACKGROUND: Epidemiological characterization in Chile points to the feminization,
      pauperization and heterosexualization of the HIV epidemic, which indicates
      increased risk for socially disadvantaged women. When the use of substances is
      added to this, the vulnerability of this group in terms of HIV is magnified.
      OBJECTIVE: To describe the use of substances in socially disadvantaged women and
      to identify HIV/AIDS risk factors associated with the use or consumption of
      substances. MATERIAL AND METHOD: 52 women were interviewed as part of the project
      "Testing an HIV prevention intervention in Chilean women" GRANT # RO1 TW 006977.
      Socio-demographic and substance use variables are described through descriptive
      statistics, and the relationship between variables is analyzed using correlation
      tests. RESULTS: The results reveal a socio-demographic profile that places women
      in a vulnerable situation regarding transmission of HIV/AIDS, with high indices
      of substance use amplifying risk. CONCLUSIONS: These finding indicate the need
      for interventions focusing on HIV prevention in women that incorporate the risks
      associated with the consumption of substances.

PMID- 21197381
TI  - Graduated Frequencies alcohol measures for monitoring consumption patterns:
      Results from an Australian national survey and a US diary validity study.
AB  - We investigate several types of graduated frequency (GF) instruments for
      monitoring drinking patterns. Two studies with 12-month GF measures and daily
      data were used: (i) the Australian 2004 National Drug Strategy Household Survey
      (n = 24,109 aged 12+; 22,546 with GF and over 8000 with yesterday data) and (ii)
      a US methodological study involving a 28-day daily diary plus GF summary measures
      drawn from the National Alcohol Survey (n = 3,025 screened, 119 eligible study
      completers). The NDSHS involved (i) "drop and collect" self-completed forms with
      random sampling methods; the Measurement study (ii) screened 3+ drinkers by
      telephone and collected 28-day drinking diaries and pre- and post-diary 28-day
      GFs. We compared mean values for the GF quantity ranges from yesterday's drinks
      (study i) and 28-day diaries (study ii), also examining volume influence. Using
      Yesterday's drinking, Australian results showed GF quantity range means close to
      arithmetic midpoints and volume effects only for the lowest two levels (1-2, and
      3-4 drinks; p < .001). U.S. calibration results on the GF using 28-day diaries
      were similar, with a volume effect only at these low quantity levels (p < .001).
      Means for the highest quantity thresholds were 23.5 drinks for the 20+ (10 gram)
      drink level (Australia) and 15.5 drinks for the 12+ (14 g) drink level (US). In
      the US study, summary GF frequency and volume were highly consistent with diary
      based counterparts. A conclusion is that algorithms for computing volume may be
      refined using validation data. We suggest measurement methods may be improved by
      taking better account of empirical drink ethanol content.

PMID- 21197382
TI  - Recognition tunneling measurement of the conductance of DNA bases embedded in
      self-assembled monolayers.
AB  - The DNA bases interact strongly with gold electrodes, complicating efforts to
      measure the tunneling conductance through hydrogen-bonded Watson Crick base
      pairs. When bases are embedded in a self-assembled alkane-thiol monolayer to
      minimize these interactions, new features appear in the tunneling data. These new
      features track the predictions of density-functional calculations quite well,
      suggesting that they reflect tunnel conductance through hydrogen-bonded base
      pairs.

PMID- 21197383
TI  - In Search of Peace: Structural Adjustment, Violence, and International Migration.
AB  - The authors analyze the effects of structural adjustment and violence on
      international migration from selected countries in Latin America by estimating a
      series of event history models that predicted the likelihood of initial migration
      to the United States as a function of the murder rate, economic openness, and
      selected controls in the country of origin. Although several theories posit a
      connection between structural economic change and violence, such a pattern held
      only in Nicaragua, where the homicide rate increased as the economy was opened to
      trade and average incomes deteriorated. Moreover, only in Nicaragua was lethal
      violence positively related to out-migration. In Mexico, Costa Rica, and
      Guatemala, rising violence reduced the likelihood of emigration. Violence does
      not appear to have uniform effects on patterns of international migration but
      depends on broader social and political conditions within particular countries.

PMID- 21197384
TI  - Identification of Intrinsic Airway Acidification in Pulmonary Tuberculosis.
AB  - Exhaled breath condensate acidification reflects the presence of airway
      acidification. Mycobacterium tuberculosis is an organism particularly sensitive
      to acidity. We aimed to determine if there is evidence of airway acidification in
      a cross section of patients with active tuberculosis.We enrolled 51 subjects with
      active tuberculosis in Ghana and Thailand, and compared them to control subjects.
      We collected exhaled breath condensate, and assayed for pH after gas
      standardization.Exhaled breath condensate pH from the control group revealed a
      median of 7.9 (7.7 - 8.0, n = 21), significantly higher than the active pulmonary
      tuberculosis patients who had a median pH of 7.4 (7.0 - 7.7; n = 51; p=0.002).
      Presence or absence of antibiotic therapy did not affect EBC pH values.These
      exhaled breath condensate data support the theory that airways become acidic in
      active tuberculosis infection. This may be a mechanism of immune response and
      pathology not previously considered.

PMID- 21197385
TI  - Successes and challenges of HIV treatment programs in Haiti: aftermath of the
      earthquake.
AB  - Haiti's HIV/AIDS program is one of the most successful in the world, with a
      declining HIV prevalence, and treatment outcomes that rival those of
      industrialized nations. It is now on the way to providing universal treatment for
      HIV/AIDS nationwide. This success is tied to a strong foundation for HIV care
      that was in place before external funding became available that includes national
      guidelines prepared by the Ministry of Health, political commitment at the
      highest levels of government, non-governmental organizations that had been
      providing high quality care in Haiti for decades, and the assistance of the
      Global Fund to Fight AIDS, TB, and Malaria, the U.S. President's Emergency Plan
      for AIDS Relief (PEPFAR) and other private donors.While the challenges of human
      resource shortages, widespread poverty, and limited infrastructure cannot be
      overstated, these are being addressed through the provision of integrated,
      comprehensive services. Haiti's successful treatment models are being duplicated
      around the world.

PMID- 21197386
TI  - METABOLIC FUNCTIONS OF MYOSTATIN AND GDF11.
AB  - Myostatin is a member of the transforming growth factor beta superfamily of
      secreted growth factors that negatively regulates skeletal muscle size. Mice null
      for the myostatin gene have a dramatically increased mass of individual muscles,
      reduced adiposity, increased insulin sensitivity, and resistance to obesity.
      Myostatin inhibition in adult mice also increases muscle mass which raises the
      possibility that anti-myostatin therapy could be a useful approach for treating
      diseases such as obesity or diabetes in addition to muscle wasting diseases. In
      this review I will describe the present state of our understanding of the role of
      myostatin and the closely related growth factor growth/differentiation factor 11
      on metabolism.

PMID- 21197387
TI  - Therapeutic Vaccines and Antibodies for Treatment of Orthopoxvirus Infections.
AB  - Despite the eradication of smallpox several decades ago, variola and monkeypox
      viruses still have the potential to become significant threats to public health.
      The current licensed live vaccinia virus-based smallpox vaccine is extremely
      effective as a prophylactic vaccine to prevent orthopoxvirus infections, but
      because of safety issues, it is no longer given as a routine vaccine to the
      general population. In the event of serious human orthopoxvirus infections, it is
      important to have treatments available for individual patients as well as their
      close contacts. The smallpox vaccine and vaccinia immune globulin (VIG) were used
      in the past as therapeutics for patients exposed to smallpox. VIG was also used
      in patients who were at high risk of developing complications from smallpox
      vaccination. Thus post-exposure vaccination and VIG treatments may again become
      important therapeutic modalities. This paper summarizes some of the historic use
      of the smallpox vaccine and immunoglobulins in the post-exposure setting in
      humans and reviews in detail the newer animal studies that address the use of
      therapeutic vaccines and immunoglobulins in orthopoxvirus infections as well as
      the development of new therapeutic monoclonal antibodies.

PMID- 21197388
TI  - Perceived School and Neighborhood Safety, Neighborhood Violence and Academic
      Achievement in Urban School Children.
AB  - Community and school violence continue to be a major public health problem,
      especially among urban children and adolescents. Little research has focused on
      the effect of school safety and neighborhood violence on academic performance.
      This study examines the effect of the school and neighborhood climate on academic
      achievement among a population of 3(rd)-5(th) grade students in an urban public
      school system. Community and school safety were assessed using the School Climate
      Survey, an annual city-wide assessment of student's perception of school and
      community safety. Community violence was measured using the Neighborhood
      Inventory for Environmental Typology, an objective observational assessment of
      neighborhood characteristics. Academic achievement was measured using the
      Maryland State Assessment (MSA), a standardized exam given to all Maryland 3(rd)
      8(th) graders. School Climate Data and MSA data were aggregated by school and
      grade. Objective assessments of neighborhood environment and students' self
      reported school and neighborhood safety were both strongly associated with
      academic performance. Increasing neighborhood violence was associated with
      statistically significant decreases from 4.2%-8.7% in math and reading
      achievement; increasing perceived safety was associated with significant
      increases in achievement from 16%-22%. These preliminary findings highlight the
      adverse impact of perceived safety and community violence exposure on primary
      school children's academic performance.

PMID- 21197389
TI  - Pd/P(t-Bu)(3)-Catalyzed Suzuki Cross-Couplings in the Presence of Water.
AB  - Pd(2)(dba)(3)/[HP(t-Bu)(3)]BF(4)/KF*2H(2)O serves as a mild, robust, and user
      friendly method for the efficient Suzuki cross-coupling of a diverse array of
      aryl and heteroaryl halides with aryl- and heteroarylboronic acids.

PMID- 21197390
TI  - Acoustically enhanced Evans blue dye perfusion in neurological tissues.

PMID- 21197391
TI  - The Impact of Experiential Avoidance on the Inference of Characters' Emotions:
      Evidence for an Emotional Processing Bias.
AB  - Experiential avoidance is a functional class of maladaptive strategies that
      contribute to the development and maintenance of psychopathology. Although
      previous research has demonstrated group differences in the interpretation of
      aversive stimuli, there is limited work on the influence of experiential
      avoidance during the online processing of emotion. An experimental design
      investigated the influence of self-reported experiential avoidance during emotion
      processing by assessing emotion inferences during the comprehension of narratives
      that imply different emotions. Results suggest that experiential avoidance is
      partially characterized by an emotional information processing bias.
      Specifically, individuals reporting higher experiential avoidance scores
      exhibited a bias towards activating negative emotion inferences, whereas
      individuals reporting lower experiential avoidance scores exhibited a bias
      towards activating positive emotion inferences. Minimal emotional inference was
      observed for the non-bias affective valence. Findings are discussed in terms of
      the implications of experiential avoidance as a cognitive vulnerability for
      psychopathology.

PMID- 21197392
TI  - Parental Timing and Depressive Symptoms in Early Adulthood.
AB  - Using data from a panel of 459 women, we find that early parents (< 20 years old
      at first birth) report higher levels of depressive symptoms in young adulthood
      (roughly age 29) compared to later parents (first birth in their 20's) or
      nonparents. Early parenting is also associated with more stressors and fewer
      resources in young adulthood. As young adults, early parents have lower
      educational attainment, less secure employment and a weaker sense of personal
      control; they also experience greater financial strain and more traumatic life
      events than later and nonparents. By the end of their twenties, early parents are
      also more likely to be single compared to late parents. The higher levels of
      depressive symptoms reported among early parents, compared to both later parents
      and nonparents, are primarily explained by their greater financial strain and
      lower sense of personal control.

PMID- 21197393
TI  - BACs as tools for the study of genomic imprinting.
AB  - Genomic imprinting in mammals results in the expression of genes from only one
      parental allele. Imprinting occurs as a consequence of epigenetic marks set down
      either in the father's or the mother's germ line and affects a very specific
      category of mammalian gene. A greater understanding of this distinctive
      phenomenon can be gained from studies using large genomic clones, called
      bacterial artificial chromosomes (BACs). Here, we review the important
      applications of BACs to imprinting research, covering physical mapping studies
      and the use of BACs as transgenes in mice to study gene expression patterns, to
      identify imprinting centres, and to isolate the consequences of altered gene
      dosage. We also highlight the significant and unique advantages that rapid BAC
      engineering brings to genomic imprinting research.

PMID- 21197394
TI  - Nasal birth trauma: a review of appropriate treatment.
AB  - The aetiology of nasal deformity has frequently included birth trauma. There is
      no consensus in the literature as to whether nasal surgery, in the form of closed
      reduction, is indicated in neonates. The majority of studies in the literature
      that advocate intervention have inadequate followup periods and there is a
      paucity of evidence for the adverse effects of conservative management. This case
      highlights the therapeutic dilemma posed by such nasal injuries in the neonate
      and, to the best of the authors' knowledge, at the time of writing, represents
      the earliest reported case in the literature of nasal deformity in the neonate.
      The term nasal deformity is used to denote deformity of the nasal pyramid, soft
      tissue, and septum. Three main aspects of neonatal nasal deformity are addressed
      including, firstly, if nasal deformity at birth needs to be addressed, secondly,
      if left unaltered, what the long-term effects are and, finally, if intervention
      alters the normal course of midfacial development.

PMID- 21197395
TI  - Development and application of bovine and porcine oligonucleotide arrays with
      protein-based annotation.
AB  - The design of oligonucleotide sequences for the detection of gene expression in
      species with disparate volumes of genome and EST sequence information has been
      broadly studied. However, a congruous strategy has yet to emerge to allow the
      design of sensitive and specific gene expression detection probes. This study
      explores the use of a phylogenomic approach to align transcribed sequences to
      vertebrate protein sequences for the detection of gene families to design
      genomewide 70-mer oligonucleotide probe sequences for bovine and porcine. The
      bovine array contains 23,580 probes that target the transcripts of 16,341 genes,
      about 72% of the total number of bovine genes. The porcine array contains 19,980
      probes targeting 15,204 genes, about 76% of the genes in the Ensembl annotation
      of the pig genome. An initial experiment using the bovine array demonstrates the
      specificity and sensitivity of the array.

PMID- 21197396
TI  - An Intron 7 Polymorphism in APP Affects the Age of Onset of Dementia in Down
      Syndrome.
AB  - People with Down syndrome (DS) develop Alzheimer's disease (AD) with an early age
      of onset. A tetranucleotide repeat, attt(5-8), in intron 7 of the amyloid
      precursor protein has been associated with the age of onset of AD in DS in a
      preliminary study. The authors examine the impact of this polymorphism in a
      larger cohort of individuals with DS. Adults with DS were genotyped for attt(5-8)
      and APOE. The results were analysed with respect to the age of onset of dementia.
      The presence of three copies of the six-repeat allele resulted in onset of
      dementia seven years earlier than in the presence of other genotypes. Further
      study is essential to elucidate the mechanism by which this polymorphism
      functions, with an exciting opportunity to identify novel treatment targets
      relevant for people with DS and AD.

PMID- 21197397
TI  - Long-term effect of mediterranean-style diet and calorie restriction on
      biomarkers of longevity and oxidative stress in overweight men.
AB  - We report the effects of a Mediterranean-style diet, with or without calorie
      restriction, on biomarkers of aging and oxidative stress in overweight men. 192
      men were randomly assigned to either a Mediterranean-style diet or a conventional
      diet. The intervention program was based on implementation of a Mediterranean
      dietary pattern in the overweight group (MED diet group), associated with calorie
      restriction and increased physical activity in the obese group (lifestyle group).
      Both groups were compared with participants in two matched control groups (advice
      groups). After 2 years, there was a significant difference in weight loss between
      groups, which was -14 kg (95% CI -20 to -8) in lifestyle groups and -2.0 kg (-4.4
      to 0) in the advice groups, with a difference of -11.9 kg (CI -19 to -4.7 kg, P <
      .001); moreover, there was a significant difference between groups at 2 years for
      insulin (P = .04), 8-iso-PGF2alpha (P = .037), glucose (P = .04), and adiponectin
      (P = .01). Prolonged adherence to a Mediterranean-style diet, with or without
      caloric restriction, in overweight or obese men is associated with significant
      amelioration of multiple risk factors, including a better cardiovascular risk
      profile, reduced oxidative stress, and improved insulin sensitivity.

PMID- 21197398
TI  - Inflammation, HIF-1, and the epigenetics that follows.
AB  - We summarize recent findings linking inflammatory hypoxia to chromatin
      modifications, in particular to repressive histone signatures. We focus on the
      role of Hypoxia-Induced Factor-1 in promoting the activity of specific histone
      demethylases thus deeply modifying chromatin configuration. The consequences of
      these changes are depicted in terms of gene expression and cellular phenotypes.
      We finally integrate available data to introduce novel speculations on the
      relationship between inflammation, histones, and DNA function and integrity.

PMID- 21197399
TI  - Expression of proinflammatory and regulatory cytokines via NF-kappaB and MAPK
      dependent and IFN regulatory factor-3-independent mechanisms in human primary
      monocytes infected by Mycobacterium tuberculosis.
AB  - Knowledge of the molecular events regulating the innate response to Mycobacterium
      tuberculosis (Mtb) is critical for understanding immunological pathogenesis and
      protection from tuberculosis. To this aim, the regulation and the expression of
      regulatory and proinflammatory cytokines were investigated in human primary
      monocytes upon Mtb infection. We found that Mtb-infected monocytes preferentially
      express a proinflammatory cytokine profile, including IL-6, TNF-alpha, and IL
      1beta. Conversely, among the regulatory cytokines, Mtb elicited IL-10 and IL-23
      release while no expression of IL-12p70, IL-27, and IFN-beta was observed. The
      analysis of the signalling pathways leading to this selective cytokine expression
      showed that in monocytes Mtb activates MAPK and NF-kappaB but is unable to
      stimulate IRF-3 phosphorylation, a transcription factor required for IL-12p35 and
      IFN-beta gene expression. Thus, by inducing a specific cytokine profile, Mtb can
      influence the immunoregulatory properties of monocytes, which represent important
      target of novel vaccinal strategies against Mtb infection.

PMID- 21197401
TI  - Incidence of stroke in young adults: a review.
AB  - Introduction. Stroke in the young may have a dramatic impact on the quality of
      life in survivors. This study was aimed to evaluate incidence of first-ever
      stroke in the young by means of a systematic review. Materials and Methods. All
      papers on incidence of stroke in the young published after 1980, were identified
      by electronic search of Medline and manual search of reference lists. Only
      studies recruiting subjects under 44 years of age and with a lower age limit not
      higher than 20 years were included. Incidence rates were standardized to the 2000
      European population according to the direct method. Poisson regression analysis
      was used to compare studies. Results. 29 studies including 3548 participants were
      identified. Incidence rates, after excluding a few outliers, ranged between 8.63
      and 19.12 for crude rates and between 8.70 and 21.02 for standardized rates.
      Heterogeneity among studies was statistically significant but improved after
      excluding 4 studies. Few studies reported the proportions of stroke subtypes.
      Conclusions. Stroke in subjects under 45 years of age is not such a rare disease
      and requires specific preventive programs.

PMID- 21197400
TI  - Kinetic approaches to understanding the mechanisms of fidelity of the herpes
      simplex virus type 1 DNA polymerase.
AB  - We discuss how the results of presteady-state and steady-state kinetic analysis
      of the polymerizing and excision activities of herpes simplex virus type 1 (HSV
      1) DNA polymerase have led to a better understanding of the mechanisms
      controlling fidelity of this important model replication polymerase. Despite a
      poorer misincorporation frequency compared to other replicative polymerases with
      intrinsic 3' to 5' exonuclease (exo) activity, HSV-1 DNA replication fidelity is
      enhanced by a high kinetic barrier to extending a primer/template containing a
      mismatch or abasic lesion and by the dynamic ability of the polymerase to switch
      the primer terminus between the exo and polymerizing active sites. The HSV-1
      polymerase with a catalytically inactivated exo activity possesses reduced rates
      of primer switching and fails to support productive replication, suggesting a
      novel means to target polymerase for replication inhibition.

PMID- 21197402
TI  - Perinatal hypoxic-ischemic encephalopathy.
AB  - Perinatal hypoxic-ischemic encephalopathy (HIE) is an important cause of brain
      injury in the newborn and can result in long-term devastating consequences.
      Perinatal hypoxia is a vital cause of long-term neurologic complications varying
      from mild behavioural deficits to severe seizure, mental retardation, and/or
      cerebral palsy in the newborn. In the mammalian developing brain, ongoing
      research into pathophysiological mechanism of neuronal injury and therapeutic
      strategy after perinatal hypoxia is still limited. With the advent of promising
      therapy of hypothermia in HIE, this paper reviews the pathophysiology of HIE and
      the future potential neuroprotective strategies for clinical potential for
      hypoxia sufferers.

PMID- 21197403
TI  - Reconstruction of protein-protein interaction network of insulin signaling in
      Homo sapiens.
AB  - Diabetes is one of the most prevalent diseases in the world. Type 1 diabetes is
      characterized by the failure of synthesizing and secreting of insulin because of
      destroyed pancreatic beta-cells. Type 2 diabetes, on the other hand, is described
      by the decreased synthesis and secretion of insulin because of the defect in
      pancreatic beta-cells as well as by the failure of responding to insulin because
      of malfunctioning of insulin signaling. In order to understand the signaling
      mechanisms of responding to insulin, it is necessary to identify all components
      in the insulin signaling network. Here, an interaction network consisting of
      proteins that have statistically high probability of being biologically related
      to insulin signaling in Homo sapiens was reconstructed by integrating Gene
      Ontology (GO) annotations and interactome data. Furthermore, within this
      reconstructed network, interacting proteins which mediate the signal from insulin
      hormone to glucose transportation were identified using linear paths. The
      identification of key components functioning in insulin action on glucose
      metabolism is crucial for the efforts of preventing and treating type 2 diabetes
      mellitus.

PMID- 21197405
TI  - Response to cardiac resynchronization therapy: the muscular metabolic pathway.
AB  - Background. Changes in peripheral muscle in heart failure lead to a shift from
      aerobic to early anaerobic metabolism during exercise leading to ergoreflex
      overactivation and exaggerated hyperventilation evaluated by the VE/VCO(2) slope.
      Methods. 50 patients (38 males, 59 +/- 12 years) performed cardio-pulmonary
      exercise test with gaz exchange measurement and echocardiographic evaluation
      before and 6 months after CRT. Results. The peak respiratory exchange (VCO(2)/
      VO(2)) ratio was significantly reduced from 1.16 +/- 0.14 to 1.11 +/- 0.07 (P <
      .05) and the time to the anaerobic threshold was increased from 153 +/- 82 to 245
      +/- 140 seconds (P = .01). Peak VO(2), VE/VCO(2), peak circulatory power and NYHA
      were improved after CRT (13 +/- 4 to16 +/- 5 ml/kg/min (P < .05), 45 +/- 16 to 39
      +/- 13 (P < .01), 1805 +/- 844 to 2225 +/- 1171 mmHg.ml/kg/min (P < .01) and 3 +/
      0.35 to 1.88 +/- 0.4 (P = .01)). In addition, left ventricular ejection fraction
      and end-systolic volumes were improved from 24 +/- 8 to 29 +/- 7% (P < .01) and
      from 157 +/- 69 to 122 +/- 55 ml (P < .01). Conclusion. We suggest that CRT leads
      to an increase in oxidative muscular metabolism and postponed anaerobic threshold
      reducing exaggerated hyperventilation during exercise.

PMID- 21197404
TI  - The role of zinc in Alzheimer's disease.
AB  - Zinc, the most abundant trace metal in the brain, has numerous functions, both in
      health and in disease. Zinc is released into the synaptic cleft of glutamatergic
      neurons alongside glutamate from where it interacts and modulates NMDA and AMPA
      receptors. In addition, zinc has multifactorial functions in Alzheimer's disease
      (AD). Zinc is critical in the enzymatic nonamyloidogenic processing of the
      amyloid precursor protein (APP) and in the enzymatic degradation of the amyloid
      beta (Abeta) peptide. Zinc binds to Abeta promoting its aggregation into
      neurotoxic species, and disruption of zinc homeostasis in the brain results in
      synaptic and memory deficits. Thus, zinc dyshomeostasis may have a critical role
      to play in the pathogenesis of AD, and the chelation of zinc is a potential
      therapeutic approach.

PMID- 21197406
TI  - Release of danger signals during ischemic storage of the liver: a potential
      marker of organ damage?
AB  - Liver grafts suffer from unavoidable injury due to ischemia and manipulation
      before implantation. Danger signals such as high-mobility group box -1(HMGB1) and
      macrophage migration inhibitory factor (MIF) play a pivotal role in the immune
      response. We characterized the kinetics of their release into the effluent during
      cold/warm ischemia and additional manipulation-induced mechanical damage.
      Furthermore, we evaluated the relationship between HMGB1/MIF release and
      ischemic/mechanical damage. Liver enzymes and protein in the effluent increased
      with increasing ischemia time. HMGB1/MIF- release correlated with the extent of
      hepatocellular injury. With increasing ischemia time and damage, HMGB1 was
      translocated from the nucleus to the cytoplasma as indicated by weak nuclear and
      strong cytoplasmic staining. Enhancement of liver injury by mechanical damage was
      indicated by an earlier HMGB1 translocation into the cytoplasm and earlier
      release of danger signals into the effluent. Our results suggest that
      determination of HMGB1 and MIF reflects the extent of ischemic injury.
      Furthermore, HMGB1 and MIF are more sensitive than liver enzymes to detect the
      additional mechanical damage inflicted on the organ graft during surgical
      manipulation.

PMID- 21197407
TI  - Renal failure associated with APECED and terminal 4q deletion: evidence of
      autoimmune nephropathy.
AB  - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare
      autosomal recessive disorder caused by mutations in the autoimmune regulator gene
      (AIRE). Terminal 4q deletion is also a rare cytogenetic abnormality that causes a
      variable syndrome of dysmorphic features, mental retardation, growth retardation,
      and heart and limb defects. We report a 12-year-old Saudi boy with mucocutaneous
      candidiasis, hypoparathyroidism, and adrenocortical failure consistent with
      APECED. In addition, he has dysmorphic facial features, growth retardation, and
      severe global developmental delay. Patient had late development of chronic renal
      failure. The blastogenesis revealed depressed lymphocytes' response to Candida
      albicans at 38% when compared to control. Chromosome analysis of the patient
      revealed 46,XY,del(4)(q33). FISH using a 4p/4q subtelomere DNA probe assay
      confirmed the deletion of qter subtelomere on chromosome 4. Parental chromosomes
      were normal. The deleted array was further defined using array CGH. AIRE full
      gene sequencing revealed a homozygous mutation namely 845_846insC. Renal biopsy
      revealed chronic interstitial nephritis with advanced fibrosis. In addition,
      there was mesangial deposition of C3, C1q, and IgM. This is, to the best of our
      knowledge, the first paper showing evidence of autoimmune nephropathy by renal
      immunofluorescence in a patient with APECED and terminal 4q deletion.

PMID- 21197408
TI  - Long-term prognosis of ischemic stroke in young adults.
AB  - There is limited information about long-term prognosis of ischemic stroke in
      young adults. Giving the potentially negative impact in physical, social, and
      emotional aspects of an ischemic stroke in young people, providing early accurate
      long-term prognostic information is very important in this clinical setting.
      Moreover, detection of factors associated with bad outcomes (death, recurrence,
      moderate-to-severe disability) help physicians in optimizing secondary prevention
      strategies. The present paper reviews the most relevant published information
      concerning long-term prognosis and predictors of unfavorable outcomes of ischemic
      stroke affecting young adults. As a summary, we can conclude that, in the long
      term, stroke in the young adult increases slightly the risk of mortality, implies
      higher risk of future cardiovascular events, and determines functional
      limitations in a significant percentage of patients. Nevertheless, in every
      individual case the prognosis has to be considered depending on several factors
      (stroke subtype, initial severity, cardiovascular risk factors) that determine
      the long-term outcomes.

PMID- 21197409
TI  - Diagnosis and prognostication of ductal adenocarcinomas of the pancreas based on
      genome-wide DNA methylation profiling by bacterial artificial chromosome array
      based methylated CpG island amplification.
AB  - To establish diagnostic criteria for ductal adenocarcinomas of the pancreas
      (PCs), bacterial artificial chromosome (BAC) array-based methylated CpG island
      amplification was performed using 139 tissue samples. Twelve BAC clones, for
      which DNA methylation status was able to discriminate cancerous tissue (T) from
      noncancerous pancreatic tissue in the learning cohort with a specificity of 100%,
      were identified. Using criteria that combined the 12 BAC clones, T-samples were
      diagnosed as cancers with 100% sensitivity and specificity in both the learning
      and validation cohorts. DNA methylation status on 11 of the BAC clones, which was
      able to discriminate patients showing early relapse from those with no relapse in
      the learning cohort with 100% specificity, was correlated with the recurrence
      free and overall survival rates in the validation cohort and was an independent
      prognostic factor by multivariate analysis. Genome-wide DNA methylation profiling
      may provide optimal diagnostic markers and prognostic indicators for patients
      with PCs.

PMID- 21197410
TI  - Atopic dermatitis-like skin lesions reduced by topical application and
      intraperitoneal injection of Hirsutenone in NC/Nga mice.
AB  - Atopic dermatitis (AD) is a common inflammatory skin disease. The increasing
      prevalence and severity of AD have prompted the developments of safer, more
      effective drugs. Although topical corticosteroids have been used as first line
      therapy for AD, their potential side effects limit their clinical applications.
      To investigate the effect of hirsutenone (HIR), a diarylheptanoid compound, on AD
      like skin lesions and other factors related to immune response is the aim of this
      paper Th2-related cytokines (IL-4, IL-5, IL-13), eosinophil, IgE inflammatory
      factors (COX-2, iNOS) levels were reduced in blood, lymphocytes, and tissue after
      HIR treatment. These results suggest that HIR might be an effective treatment for
      AD.

PMID- 21197411
TI  - Characteristics of highly polymorphic segmental copy-number variations observed
      in Japanese by BAC-array-CGH.
AB  - Segmental copy-number variations (CNVs) may contribute to genetic variation in
      humans. Reports of the existence and characteristics of CNVs in a large Japanese
      cohort are quite limited. We report the data from a large Japanese population. We
      conducted population screening for 213 unrelated Japanese individuals using
      comparative genomic hybridization based on a bacterial artificial chromosome
      microarray (BAC-aCGH). We summarize the data by focusing on highly polymorphic
      CNVs in >=5.0% of the individual, since they may be informative for demonstrating
      the relationships between genotypes and their phenotypes. We found a total of 680
      CNVs at 16 different BAC-regions in the genome. The majority of the polymorphic
      CNVs presented on BAC-clones that overlapped with regions of segmental
      duplication, and the majority of the polymorphic CNVs observed in this population
      had been previously reported in other publications. Some of the CNVs contained
      genes which might be related to phenotypic heterogeneity among individuals.

PMID- 21197412
TI  - Androidal fat dominates in predicting cardiometabolic risk in postmenopausal
      women.
AB  - We hypothesized that soy isoflavones would attenuate the anticipated increase in
      androidal fat mass in postmenopausal women during the 36-month treatment, and
      thereby favorably modify the circulating cardiometabolic risk factors:
      triacylglycerol, LDL-C, HDL-C, glucose, insulin, uric acid, C-reactive protein,
      fibrinogen, and homocysteine. We collected data on 224 healthy postmenopausal
      women at risk for osteoporosis (45.8-65 y, median BMI 24.5) who consumed placebo
      or soy isoflavones (80 or 120 mg/d) for 36 months and used longitudinal analysis
      to examine the contribution of isoflavone treatment, androidal fat mass, other
      biologic factors, and dietary quality to cardiometabolic outcomes. Except for
      homocysteine, each cardiometabolic outcome model was significant (overall P
      values from <=.0001 to .0028). Androidal fat mass was typically the strongest
      covariate in each model. Isoflavone treatment did not influence any of the
      outcomes. Thus, androidal fat mass, but not isoflavonetreatment, is likely to
      alter the cardiometabolic profile in healthy postmenopausal women.

PMID- 21197413
TI  - Helicobacter pylori eradication lowers serum asymmetric dimethylarginine levels.
AB  - INTRODUCTION: Microbial pathogens, one of them is Helicobacter pylori (H.
      pylori), have frequently been implicated in the atherogenesis. Endothelium
      derived nitric oxide (NO) is synthesized from L-arginine by nitric oxide synthase
      (NOS) and plays a pivotal role in the regulation of vascular tone. Asymmetric
      dimethylarginine (ADMA) is the most potent endogenous NOS inhibitor. Elevated
      levels of ADMA have been reported in many circumstances associated with a high
      cardiovascular risk. The aim of the present study was to investigate whether the
      eradication of H. pylori infection affects serum ADMA levels. MATERIALS AND
      METHODS: Forty-two H. pylori-positive patients were enrolled in the study. Triple
      therapy for 14 days were given to all patients. Serum ADMA levels were measured
      at baseline and 2 months after therapy. RESULTS: Eradication was achieved in 34
      (81%) patients. The mean serum ADMA levels before and after therapy were 1, 77 +/
      0, 30 and 1, 67 +/- 0, 29 ng/mL in the group with H. pylori eradicated and 1, 63
      +/- 0, 28 and 1, 56 +/- 0, 32 ng/mL in the noneradicated, respectively. We
      detected statistically significant decreased serum ADMA levels after therapy in
      H. pylori eradicated group. CONCLUSION: These findings have indicated that
      eradication of H. pylori infection may decrease the risk of atherosclerosis and
      cardiovascular events.

PMID- 21197414
TI  - BAC modification through serial or simultaneous use of CRE/Lox technology.
AB  - Bacterial Artificial Chromosomes (BACs) are vital tools in mouse genomic analyses
      because of their ability to propagate large inserts. The size of these
      constructs, however, prevents the use of conventional molecular biology
      techniques for modification and manipulation. Techniques such as recombineering
      and Cre/Lox methodologies have thus become heavily relied upon for such purposes.
      In this work, we investigate the applicability of Lox variant sites for serial
      and/or simultaneous manipulations of BACs. We show that Lox spacer mutants are
      very specific, and inverted repeat variants reduce Lox reaction rates through
      reducing the affinity of Cre for the site, while retaining some functionality.
      Employing these methods, we produced serial modifications encompassing four
      independent changes which generated a mouse HoxB BAC with fluorescent reporter
      proteins inserted into four adjacent Hox genes. We also generated specific,
      simultaneous deletions using combinations of spacer variants and inverted repeat
      variants. These techniques will facilitate BAC manipulations and open a new
      repertoire of methods for BAC and genome manipulation.

PMID- 21197415
TI  - Development of a serum biomarker assay that differentiates tumor-associated
      MUC5AC (NPC-1C ANTIGEN) from normal MUC5AC.
AB  - A serum ELISA using a monoclonal antibody that detects a MUC5AC-related antigen
      (NPC-1C antigen) expressed by pancreatic and colorectal cancer was developed. The
      NPC-1C antibody reacts with specific epitopes expressed by tumor-associated
      MUC5AC that does not appear on MUC5AC from normal tissues. Based on observations
      of a highly specific antibody, we tested the ELISA to differentiate serum from
      healthy blood donors compared to serum from patients with colorectal or
      pancreatic cancer. Additionally, patient tumor tissue was stained to examine the
      expression pattern of MUC5AC-related antigen in pancreatic and colorectal
      cancers. The results indicate the NPC-1C antibody ELISA distinguished serum of
      cancer patients from normal donors with very good sensitivity and specificity.
      Most patient's tumor biopsy exhibited NPC-1C antibody reactivity, indicating that
      tumor-associated MUC5AC antigen from tumor is shed into blood, where it can be
      detected by the NPC-1C antibody ELISA. This serum test provides a new tool to aid
      in the diagnosis of these cancers and immune monitoring of cancer treatment
      regimens.

PMID- 21197416
TI  - SEGMENTING CT PROSTATE IMAGES USING POPULATION AND PATIENT-SPECIFIC STATISTICS
      FOR RADIOTHERAPY.
AB  - This paper presents a new deformable model using both population and patient
      specific statistics to segment the prostate from CT images. There are two
      novelties in the proposed method. First, a modified scale invariant feature
      transform (SIFT) local descriptor, which is more distinctive than general
      intensity and gradient features, is used to characterize the image features.
      Second, an online training approach is used to build the shape statistics for
      accurately capturing intra-patient variation, which is more important than inter
      patient variation for prostate segmentation in clinical radiotherapy.
      Experimental results show that the proposed method is robust and accurate,
      suitable for clinical application.

PMID- 21197417
TI  - Pegylated IFN-alpha sensitizes melanoma cells to chemotherapy and causes
      premature senescence in endothelial cells by IRF-1 mediated signaling.
AB  - Pegylated Interferon-alpha2b (pIFN-alpha) is an integral part of the drug regimen
      currently employed against melanoma. Interferon Regulatory Factor-1 (IRF-1) plays
      an important role in the transcriptional regulation of the IFN response, cell
      cycle and apoptosis. We have studied pIFN-alpha induced responses when combined
      with the chemotherapy agent, vinblastine in tumor and endothelial cell lines and
      the connection to IRF-1 signaling. Levels of IRF-1/IRF-2 protein expression were
      found to be decreased in tumor versus normal tissues. pIFN-alpha induced IRF-1
      signaling in human melanoma (M14) and endothelial (EA.hy926) cells and enhanced
      cell death when combined with vinblastine. Upon combined IFN-alpha and
      vinblastine treatment, p21 expression, PARP cleavage and activated Bak levels
      were increased in M14 cells. An increase in p21 and cyclin D1 expression occurred
      in EA.hy926 cells after 6 h of treatment with pIFN-alpha which dissipated by 24
      h. This biphasic response, characteristic of cellular senescence, was more
      pronounced upon combined treatment. Exposure of the EA.hy926 cells to pIFN-alpha
      was associated with an enlarged, multinucleated, beta-galactosidase-positive
      senescent phenotype. The overall therapeutic mechanism of IFN-alpha combined with
      chemotherapy may be due to both direct tumor cell death via IRF-1 signaling and
      by premature senescence of endothelial cells and subsequent effects on
      angiogenesis in the tumor microenvironment.

PMID- 21197418
TI  - From Singing to Speaking: Why Singing May Lead to Recovery of Expressive Language
      Function in Patients with Broca's Aphasia.
AB  - It has been reported that patients with severely nonfluent aphasia are better at
      singing lyrics than speaking the same words. This observation inspired the
      development of Melodic Intonation Therapy (MIT), a treatment whose effects have
      been shown, but whose efficacy is unproven and neural correlates remain
      unidentified. Because of its potential to engage/unmask language-capable regions
      in the unaffected right hemisphere, MIT is particularly well suited for patients
      with large left-hemisphere lesions. Using two patients with similar impairments
      and stroke size/location, we show the effects of MIT and a control intervention.
      Both interventions' post-treatment outcomes revealed significant improvement in
      propositional speech that generalized to unpracticed words and phrases; however,
      the MIT-treated patient's gains surpassed those of the control-treated patient.
      Treatment-associated imaging changes indicate that MIT's unique engagement of the
      right hemisphere, both through singing and tapping with the left hand to prime
      the sensorimotor and premotor cortices for articulation, accounts for its effect
      over nonintoned speech therapy.

PMID- 21197419
TI  - CHILD AND MOTHER PLAY IN SOUTH KOREA: A LONGITUDINAL STUDY ACROSS THE SECOND YEAR
      OF LIFE.
AB  - Play is a predominant individual and social activity of early childhood and has
      been related to young children's early cognitive growth, social development, and
      preparation for formal schooling. We examined individual differences and
      developmental changes in South Korean child and mother exploratory and symbolic
      play longitudinally when children were 13 and 20 months of age. Children engaged
      in less exploratory and more symbolic play when playing collaboratively with
      their mothers than when playing alone. Children engaged in more symbolic play at
      20 months than 13 months. Child solitary and collaborative symbolic play was
      modestly stable across time, but child exploratory play and maternal play were
      not. Child solitary and collaborative symbolic play were correlated across the
      two ages. Child and mother play were regularly associated at the two ages, and 13
      month maternal play predicted 20-month child collaborative play. The cross
      cultural validity of play is affirmed, and individual differences and age-related
      changes in child and mother play are partly mediated by matched partner play and
      partly motivated by processes independent of partner play.

PMID- 21197420
TI  - Who Are We, But for the Stories We Tell: Family Stories and Healing.
AB  - Storytelling is a notable part of family life. Families share stories that
      illuminate and combine their separate experiences into a meaningful whole.
      Families narrate both their best and worst life experiences and in this way pass
      down a heritage of remembrances from one generation to the next. Clinicians
      working with families who have been impacted by trauma can use family
      storytelling to aid healing. This article reviews the functions of family
      storytelling and the skills used by family members in the act of storying to
      illustrate how therapists can facilitate families' use of their storytelling
      skills in the healing process.

PMID- 21197421
TI  - Spatial analysis of feline immunodeficiency virus infection in cougars.
AB  - The cougar (Puma concolor) is a large predatory feline found widely in the
      Americas that is susceptible to feline immunodeficiency virus (FIV), a fast
      evolving lentivirus found in wild feline species that is analogous to simian
      immunodeficiency viruses in wild primates and belongs to the same family of
      viruses as human immunodeficiency virus. FIV infection in cougars can lead to a
      weakened immune system that creates opportunities for other infecting agents. FIV
      prevalence and lineages have been studied previously in several areas in the
      western United States, but typically without spatially explicit statistical
      techniques. To describe the distribution of FIV in a sample of cougars located in
      the northern Rocky Mountain region of North America, we first used kernel density
      ratio estimation to map the log relative risk of FIV. The risk surface showed a
      significant cluster of FIV in northwestern Montana. We also used Bayesian cluster
      models for genetic data to investigate the spatial structure of the feline
      immunodeficiency virus with virus genetic sequence data. A result of the models
      was two spatially distinct FIV lineages that aligned considerably with an
      interstate highway in Montana. Our results suggest that the use of spatial
      information and models adds novel insight when investigating an infectious animal
      disease. The results also suggest that the influence of landscape features likely
      plays an important role in the spatiotemporal spread of an infectious disease
      within wildlife populations.

PMID- 21197422
TI  - Consistency of Normal Distribution Based Pseudo Maximum Likelihood Estimates When
      Data Are Missing at Random.
AB  - This paper shows that, when variables with missing values are linearly related to
      observed variables, the normal-distribution-based pseudo MLEs are still
      consistent. The population distribution may be unknown while the missing data
      process can follow an arbitrary missing at random mechanism. Enough details are
      provided for the bivariate case so that readers having taken a course in
      statistics/probability can fully understand the development. Sufficient
      conditions for the consistency of the MLEs in higher dimensions are also stated,
      while the details are omitted.

PMID- 21197423
TI  - The impact of transcriptomics on the fight against tuberculosis: focus on
      biomarkers, BCG vaccination, and immunotherapy.
AB  - In 1882 Robert Koch identified Mycobacterium tuberculosis as the causative agent
      of tuberculosis (TB), a disease as ancient as humanity. Although there has been
      more than 125 years of scientific effort aimed at understanding the disease,
      serious problems in TB persist that contribute to the estimated 1/3 of the world
      population infected with this pathogen. Nonetheless, during the first decade of
      the 21st century, there were new advances in the fight against TB. The
      development of high-throughput technologies is one of the major contributors to
      this advance, because it allows for a global vision of the biological phenomenon.
      This paper analyzes how transcriptomics are supporting the translation of basic
      research into therapies by resolving three key issues in the fight against TB:
      (a) the discovery of biomarkers, (b) the explanation of the variability of
      protection conferred by BCG vaccination, and (c) the development of new
      immunotherapeutic strategies to treat TB.

PMID- 21197424
TI  - Impact of moderate to severe renal impairment on mortality and appropriate shocks
      in patients with implantable cardioverter defibrillators.
AB  - Background. Due to underrepresentation of patients with chronic kidney disease
      (CKD) in large Implantable-Cardioverter Defibrillator (ICD) clinical trials, the
      impact of ICD remains uncertain in this population. Methods. Consecutive patients
      who received ICD at Creighton university medical center between years 2000-2004
      were included in a retrospective cohort after excluding those on maintenance
      dialysis. Based on baseline Glomerular filtration rate (GFR), patients were
      classified as severe CKD: GFR < 30 mL/min; moderate CKD: GFR: 30-59 mL/min; and
      mild or no CKD: GFR >= 60 mL/min. The impact of GFR on appropriate shocks and
      survival was assessed using Kaplan-Meier method and Generalized Linear Models
      (GLM) with log-link function. Results. There were 509 patients with a mean follow
      up of 3.0 + 1.3 years. Mortality risk was inversely proportional to the estimated
      GFR: 2 fold higher risk with GFR between 30-59 mL/min and 5 fold higher risk with
      GFR < 30 mL/min. One hundred and seventy-seven patients received appropriate
      shock(s); appropriate shock-free survival was lower in patients with severe CKD
      (GFR < 30) compared to mild or no CKD group (2.8 versus 4.2 yrs). Conclusion.
      Even moderate renal dysfunction increases all cause mortality in CKD patients
      with ICD. Severe but not moderate CKD is an independent predictor for time to
      first appropriate shock.

PMID- 21197426
TI  - Surgical treatment of a giant liposarcoma in a Japanese man.
AB  - We report a case of a rapidly progressing giant retroperitoneal liposarcoma
      weighing 22 kg in a 41-year-old Japanese man, successfully treated with surgical
      excision. To our knowledge, this is the largest liposarcoma in the Japanese
      population reported in the literature.

PMID- 21197425
TI  - Current views of toll-like receptor signaling pathways.
AB  - On microbial invasion, the host immediately evokes innate immune responses.
      Recent studies have demonstrated that Toll-like receptors (TLRs) play crucial
      roles in innate responses that lead not only to the clearance of pathogens but
      also to the efficient establishment of acquired immunity by directly detecting
      molecules from microbes. In terms of intracellular TLR-mediated signaling
      pathways, cytoplasmic adaptor molecules containing Toll/IL-1R (TIR) domains play
      important roles in inflammatory immune responses through the production of
      proinflammatory cytokines, nitric oxide, and type I interferon, and upregulation
      of costimulatory molecules. In this paper, we will describe our current
      understanding of the relationship between TLRs and their ligands derived from
      pathogens such as viruses, bacteria, fungi, and parasites. Moreover, we will
      review the historical and current literature to describe the mechanisms behind
      TLR-mediated activation of innate immune responses.

PMID- 21197427
TI  - Zingiber officinale Mitigates Brain Damage and Improves Memory Impairment in
      Focal Cerebral Ischemic Rat.
AB  - Cerebral ischemia is known to produce brain damage and related behavioral
      deficits including memory. Recently, accumulating lines of evidence showed that
      dietary enrichment with nutritional antioxidants could reduce brain damage and
      improve cognitive function. In this study, possible protective effect of Zingiber
      officinale, a medicinal plant reputed for neuroprotective effect against
      oxidative stress-related brain damage, on brain damage and memory deficit induced
      by focal cerebral ischemia was elucidated. Male adult Wistar rats were
      administrated an alcoholic extract of ginger rhizome orally 14 days before and 21
      days after the permanent occlusion of right middle cerebral artery (MCAO).
      Cognitive function assessment was performed at 7, 14, and 21 days after MCAO
      using the Morris water maze test. The brain infarct volume and density of neurons
      in hippocampus were also determined. Furthermore, the level of malondialdehyde
      (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase
      (GSH-Px) in cerebral cortex, striatum, and hippocampus was also quantified at the
      end of experiment. The results showed that cognitive function and neurons density
      in hippocampus of rats receiving ginger rhizome extract were improved while the
      brain infarct volume was decreased. The cognitive enhancing effect and
      neuroprotective effect occurred partly via the antioxidant activity of the
      extract. In conclusion, our study demonstrated the beneficial effect of ginger
      rhizome to protect against focal cerebral ischemia.

PMID- 21197428
TI  - The long-term effects of prematurity and intrauterine growth restriction on
      cardiovascular, renal, and metabolic function.
AB  - Objective. To determine relative influences of intrauterine growth restriction
      (IUGR) and preterm birth on risks of cardiovascular, renal, or metabolic
      dysfunction in adolescent children. Study Design. Retrospective cohort study. 71
      periadolescent children were classified into four groups: premature small for
      gestational age (SGA), premature appropriate for gestational age (AGA), term SGA,
      and term AGA. Outcome Measures. Systolic blood pressure (SBP), augmentation index
      (Al), glomerular filtration rate (GFR) following protein load; plasma glucose and
      serum insulin levels. Results. SGA had higher SBP (average 4.6 mmHg) and lower
      GFR following protein load (average 28.5 mL/min/1.73 m(2)) than AGA. There was no
      effect of prematurity on SBP (P = .4) or GFR (P = .9). Both prematurity and SGA
      were associated with higher AI (average 9.7%) and higher serum insulin levels 2
      hr after glucose load (average 15.5 mIU/L) than all other groups. Conclusion.
      IUGR is a more significant risk factor than preterm birth for later systolic
      hypertension and renal dysfunction. Among children born preterm, those who are
      also SGA are at increased risk of arterial stiffness and metabolic dysfunction.

PMID- 21197429
TI  - The effect of oral leucine on protein metabolism in adolescents with type 1
      diabetes mellitus.
AB  - Lack of insulin results in a catabolic state in subjects with insulin-dependent
      diabetes mellitus which is reversed by insulin treatment. Amino acid supply,
      especially branched chain amino acids such as leucine, enhances protein synthesis
      in both animal and human studies. This small study was undertaken to assess the
      acute effect of supplemental leucine on protein metabolism in adolescents with
      type 1 diabetes. L-[1-(13)C] Leucine was used to assess whole-body protein
      metabolism in six adolescent females (16-18 yrs) with type 1 diabetes during
      consumption of a basal diet (containing 58 MUmoles leucine/kg/h) and the basal
      diet with supplemental leucine (232 MUmoles leucine/kg/h). Net leucine balance
      was significantly higher with supplemental leucine (56.33 +/- 12.13 MUmoles
      leucine/kg body weight/hr) than with the basal diet (-11.7 +/- -5.91, P < .001)
      due to reduced protein degradation (49.54 +/- 18.80 MUmoles leucine/kg body
      weight/hr) compared to the basal diet (109 +/- 13.05, P < .001).

PMID- 21197430
TI  - Survival of viral biowarfare agents in disinfected waters.
AB  - Protecting civilian and military water supplies has received more attention since
      the United States began its war on terror in 2001. Both chlorine and bromine are
      used by branches of the U.S. military for disinfecting water supplies; however,
      limited data exists as to the effectiveness of these additives when used against
      viral biowarfare agents. The present study sought to evaluate the survival of
      selected viral biothreat agents in disinfected water. Disinfected water samples
      were spiked with vaccinia virus strain WR and Venezuelan equine encephalitis
      (VEE) virus strain TC-83 each separately to a final concentration of
      approximately 1 * 10(6) PFU/mL, and survival was assessed by plaque assay. Both
      viruses were inactivated by 1 mg/L free available chlorine (FAC) and 2mg/L total
      bromine within one hour. In conclusion, these results demonstrate that both
      chlorine and bromine are effective disinfectants against vaccinia virus and VEE
      strain TC-83 at the concentrations tested.

PMID- 21197432
TI  - Neuroinflammation Screening in Immunotherapy Trials against Alzheimer's Disease.
AB  - Due to side effects in the form of meningoencephalitis in the interrupted phase
      II AN1792 trial of active antiamyloid beta(Abeta) immunization against
      Alzheimer's disease (AD), there has been concern that anti-Abeta immunization may
      cause destructive neuroinflammation. Here, we report on two patients fulfilling
      clinical AD criteria who were diagnosed with Lyme neuroborreliosis during
      screening before inclusion in anti-Abeta immunotherapy trials. The two cases
      illustrate the necessity of careful biochemical screening for
      neuroinflammatory/neuroinfectious conditions before an AD diagnosis is made and
      before clinical AD patients are included in trials of therapy that could impact
      the immune system. Should the two cases have been included and deteriorated,
      additional investigations might have led to the erroneous conclusion that therapy
      induced meningoencephalitis had occurred.

PMID- 21197431
TI  - Biomarkers of Alzheimer's disease: from central nervous system to periphery?
AB  - Alzheimer's Disease (AD) is the most frequent form of dementia and represents one
      of the main causes of disability among older subjects. Up to now, the diagnosis
      of AD has been made according to clinical criteria. However, the use of such
      criteria does not allow an early diagnosis, as pathological alterations may be
      apparent many years before the clear-cut clinical picture. An early diagnosis is
      even more valuable to develop new treatments, potentially interfering with the
      pathogenetic process. During the last decade, several neuroimaging and
      cerebrospinal fluid (CSF) parameters have been introduced to allow an early and
      accurate detection of AD patients, and, recently, they have been included among
      research criteria for AD diagnosis. However, their use in clinical practice
      suffers from limitations both in accuracy and availability. The increasing amount
      of knowledge about peripheral biomarkers will possibly allow the future
      identification of reliable and easily available diagnostic tests.

PMID- 21197433
TI  - Fish Consumption Moderates Depressive Symptomatology in Elderly Men and Women
      from the IKARIA Study.
AB  - Background. The aim was to examine the association of depressive symptoms with
      fish eating habits, in elderly individuals. Methods. From June to October of
      2009, we studied 330 men and 343 women, aged 65 to 100 years, permanent
      inhabitants of Ikaria Island. Among several characteristics, depression was
      assessed with the Geriatric Depression scale (GDS range 0-15), while dietary
      habits through a valid semiquantitative food frequency questionnaire. Results.
      Women had significantly higher values of the GDS compared to men (4.8 +/- 3.5
      versus 3.3 +/- 3.1, P = .001). Participants in the upper tertile of depression
      scale ate less frequent fish and consumed higher quantities of alcohol, compared
      to those in the lowest tertile (all P < .05). Regarding fish consumption, 50% of
      the individuals reported consuming 1-2 times weekly, 32% 3 to 5 times weekly, 11%
      2-3 times monthly, while the rest reported rare (4.5%) and everyday (1.2%)
      consumption. Logistic regression showed that increased fish consumption (>3
      times/week versus never/rare) was inversely associated with the odds of having
      GDS greater the median value (i.e., 4) (odds  ratio = 0.34, 95% CI: 0.19, 0.61),
      after controlling for several cofounders. Conclusion. Frequent fish consumption
      in elderly seems to moderate depression mood.

PMID- 21197434
TI  - Segmental odontomaxillary dysplasia: review of the literature and case report.
AB  - Segmental Odontomaxillary Dysplasia (SOD) is an uncommon, nonhereditary, recently
      recognized developmental disorder affecting the upper jaw and related dental
      components. It is a rare condition of uncertain etiology that results in painless
      unilateral expansion of the posterior dentoalveolar complex, gingival
      hyperplasia, lack of one or both premolars in the affected area, delayed eruption
      of adjacent teeth and malformations of the primary molars. Radiographically, the
      affected bone is thickened and irregular in outline, with coarse trabecular
      pattern that is vertically oriented resulting in a relatively radiopaque granular
      appearance. Only a few cases have been reported in the English literature.
      Considering the rarity of the condition, we report a case of SOD in a pediatric
      patient who was followed up over a period of over two years. The clinical,
      radiographic, and histologic features are presented along with a review of the
      literature.

PMID- 21197435
TI  - Pleomorphic giant cell carcinoma of the pancreas with hepatic metastases-
      initially presenting as a benign serous cystadenoma: a case report and review of
      the literature.
AB  - INTRODUCTION: Pleomorphic giant cell pancreatic cancer is a very rare and
      aggressive pancreatic neoplasm. A case of pleomorphic giant cell pancreatic
      cancer presenting as a cystic lesion and in association with a serous cystadenoma
      presents a unique case which has not been described before. CASE PRESENTATION: A
      44-year-old alcoholic man presented with abdominal pain, vomiting, and weight
      loss. Initially, imaging suspected a pancreatic pseudocyst measuring 4.2 cm.
      Endoscopic ultrasound- (EUS-) guided fine-needle aspiration revealed a serous
      cystadenoma. With conservative intervention only (fluid resuscitation, analgesia,
      and antiemetics) the patient improved and was discharged under close observation.
      Follow-up scan at four months revealed minimal change. Three months later, he was
      admitted acutely. Repeat scans demonstrated mild cyst enlargement with new liver
      lesions. Laparoscopic biopsy revealed pleomorphic giant cell carcinoma with the
      organ of origin the pancreas. CONCLUSION: This unusual case highlights the
      challenges in managing pancreatic cystic lesions and emphasizes the importance of
      considering less common forms of pancreatic cystic masses when the findings are
      atypical for the presentation. Surgical excision in these cases over conservative
      steps may be the most appropriate management.

PMID- 21197436
TI  - Synthesis of Peptides from alpha- and beta-Tubulin Containing Glutamic Acid Side
      Chain Linked Oligo-Glu with Defined Length.
AB  - Side-chain oligo- and polyglutamylation represents an important posttranslational
      modification in tubulin physiology. The particular number of glutamate units is
      related to specific regulatory functions. In this work, we present a method for
      the synthesis of building blocks for the Fmoc synthesis of peptides containing
      main chain glutamic acid residues that carry side-chain branching with oligo
      glutamic acid. The two model peptide sequences CYEEVGVDSVEGEG-E(E(x))-EEGEEY and
      CQDATADEQG-E(E(x))-FEEEEGEDEA from the C-termini of mammalian alpha1- and beta1
      tubulin, respectively, containing oligo-glutamic acid side-chain branching with
      lengths of 1 to 5 amino acids were assembled in good yield and purity. The
      products may lead to the generation of specific antibodies which should be
      important tools for a more detailed investigation of polyglutamylation processes.

PMID- 21197437
TI  - Intraoperative PTH Assay during Minimally Invasive Parathyroidectomy May Be
      Helpful in the Detection of Double Adenomas and May Minimise the Risk of
      Recurrent Surgery.
AB  - Background. Minimally invasive parathyroidectomy (MIP) is increasingly replacing
      the traditional bilateral neck exploration in the treatment of primary
      hyperparathyroidism (PHP). Intraoperative PTH (IOPTH) measurement has recently
      been introduced as a useful adjunct in confirming successful excision of abnormal
      parathyroid gland. Aims. We evaluate the safety, efficacy, and clinical
      usefulness of IOPTH measurement during MIP in a district general hospital.
      Methods. Retrospective review of eleven consecutive patients with PHP who
      underwent MIP with IOPTH, following preoperative assessment with ultrasound and
      sestamibi scans. Results. All patients had successful removal of the abnormal
      parathyroid gland. The concordance rate between ultrasound and sestamibi scan in
      localising the parathyroid adenoma was 82%. IOPTH measurement confirmed the
      removal of adenoma in all cases and, in one case, led to identification of a
      second adenoma, not localised preoperatively. The median hospital stay was 2 days
      (range 1-7 days). All patients remained normocalcaemic after a median of 6 months
      (range 1-10 months). Conclusions. Minimally invasive parathyroidectomy is a
      feasible, safe, and effective method for treatment of PHP. The use of IOPTH
      monitoring potentially offers increased sensitivity in detecting multiglandular
      disease, can minimise the need and risk associated with recurrent operations, and
      may facilitate cost-effective minimally invasive surgery.

PMID- 21197438
TI  - Animal models of chronic pancreatitis.
AB  - Animal models for CP in rats can be classified into 2 groups: one is noninvasive
      or nonsurgical models and the other is invasive or surgical models. Pancreatic
      injury induced by repetitive injections of supramaximal stimulatory dose of
      caerulein (Cn) or by intraductal infusion of sodium taurocholate (NaTc) recovered
      within 14 days, whereas that caused by repetitive injection of arginine or by
      intraductal infusion of oleic acid was persistent. However, the destroyed acinar
      tissues were replaced by fatty tissues without fibrosis. Transient stasis of
      pancreatic fluid flow by 0.01% agarose and minimum injury of the pancreatic duct
      by 0.1% NaTc solution induced progressive pancreatic injury although one alone is
      insufficient to cause persistent pancreatic injury. However, the damaged tissue
      was replaced by fatty tissue without fibrosis. Continuous pancreatic ductal
      hypertension (PDH) caused diffuse interlobular and intralobular fibrosis closely
      resembling human CP.

PMID- 21197439
TI  - Immunopathology of postprimary tuberculosis: increased T-regulatory cells and DEC
      205-positive foamy macrophages in cavitary lesions.
AB  - Postprimary tuberculosis occurs in immunocompetent people infected with
      Mycobacterium tuberculosis. It is restricted to the lung and accounts for 80% of
      cases and nearly 100% of transmission. Little is known about the immunopathology
      of postprimary tuberculosis due to limited availability of specimens. Tissues
      from 30 autopsy cases of pulmonary tuberculosis were located. Sections of
      characteristic lesions of caseating granulomas, lipid pneumonia, and cavitary
      stages of postprimary disease were selected for immunohistochemical studies of
      macrophages, lymphocytes, endothelial cells, and mycobacterial antigens. A higher
      percentage of cells in lipid pneumonia (36.1%) and cavitary lesions (27.8%) were
      positive for the dendritic cell marker DEC-205, compared to granulomas (9.0%, P <
      .05). Cavities contained significantly more T-regulatory cells (14.8%) than found
      in lipid pneumonia (5.2%) or granulomas (4.8%). Distribution of the immune cell
      types may contribute to the inability of the immune system to eradicate
      tuberculosis.

PMID- 21197440
TI  - An improved harvest and in vitro expansion protocol for murine bone marrow
      derived mesenchymal stem cells.
AB  - Compared to bone marrow (BM) derived mesenchymal stem cells (MSCs) from human
      origin or from other species, the in vitro expansion and purification of murine
      MSCs (mMSCs) is much more difficult because of the low MSC yield and the unwanted
      growth of non-MSCs in the in vitro expansion cultures. We describe a modified
      protocol to isolate and expand murine BM derived MSCs based on the combination of
      mechanical crushing and collagenase digestion at the moment of harvest, followed
      by an immunodepletion step using microbeads coated with CD11b, CD45 and CD34
      antibodies. The number of isolated mMSCs as estimated by colony forming unit
      fibroblast (CFU-F) assay showed that this modified isolation method could yield
      70.0% more primary colonies. After immunodepletion, a homogenous mMSC population
      could already be obtained after two passages. Immunodepleted mMSCs (ID-mMSCs) are
      uniformly positive for stem cell antigen-1 (Sca-1), CD90, CD105 and CD73 cell
      surface markers, but negative for the hematopoietic surface markers CD14, CD34
      and CD45. Moreover the immunodepleted cell population exhibits more
      differentiation potential into adipogenic, osteogenic and chondrogenic lineages.
      Our data illustrate the development of an efficient and reliable expansion
      protocol increasing the yield and purity of mMSCs and reducing the overall
      expansion time.

PMID- 21197441
TI  - Sinonasal schwannoma with new bone formation expressing bone morphogenic protein.
AB  - Schwannoma is a benign tumor that arises from the sheath of myelinated nerve
      fibers and may occur in any part of the body. Osteogenesis in schwannoma is
      extremely rare and, to date, new bone formation in sinonasal schwannoma has not
      yet been reported. Here, we describe the first reported case of sinonasal
      schwannoma with new bone formation. The tumor was successfully treated by
      endoscopic sinus surgery, and the patient showed no evidence of recurrence 24
      months postoperatively. Immunohistochemically, the tumor expressed bone
      morphogenic protein 4, indicating a possible role of this protein in the new bone
      formation in schwannomas.

PMID- 21197442
TI  - Review of Outcome Information in 46,XX Patients with Congenital Adrenal
      Hyperplasia Assigned/Reared Male: What Does It Say about Gender Assignment?
AB  - There is ample historical verification of 46,XX congenital adrenal hyperplasia
      (CAH) patients being born with essentially male genitaliawhile outcome
      information is scant. Prior to glucocorticoid therapy, most patients died very
      young from adrenal insufficiency. Most available reports from laterchildhood,
      contain little information concerning sexual identity. Reports on older
      individuals lack adequate information about sexual identity and quality of life.
      The difficulty in assessing the relative impact of multiple dynamic environmental
      factors on the development of sexual identity, self- and body esteem and overall
      adjustment to life is clear. Nevertheless, it remains unclear whether those
      infants whose masculine genitalia at birth resulted in an initial male assignment
      would have enjoyed a better adult outcome had they been allowed to remain male
      rather than the female reassignment that most received. Further, one could ask
      whether a male sex of rearing should be considered in 46,XX CAH infants with male
      external genitalia. After reviewing available literature, we conclude that
      because those extremely virlized 46,XX CAH patients who were reared male with
      healthy social support demonstrated satisfactory levels of social and sexual
      function as adults a male sex assignment should be considered in these types of
      infants when social and cultural environment are supportive.

PMID- 21197443
TI  - Characterization of pPCP1 Plasmids in Yersinia pestis Strains Isolated from the
      Former Soviet Union.
AB  - Complete sequences of 9.5-kb pPCP1 plasmids in three Yersinia pestis strains from
      the former Soviet Union (FSU) were determined and compared with those of pPCP1
      plasmids in three well-characterized, non-FSU Y. pestis strains (KIM, CO92, and
      91001). Two of the FSU plasmids were from strains C2614 and C2944, isolated from
      plague foci in Russia, and one plasmid was from strain C790 from Kyrgyzstan.
      Sequence analyses identified four sequence types among the six plasmids. The
      pPCP1 plasmids in the FSU strains were most genetically related to the pPCP1
      plasmid in the KIM strain and least related to the pPCP1 plasmid in Y. pestis
      91001. The FSU strains generally had larger pPCP1 plasmid copy numbers compared
      to strain CO92. Expression of the plasmid's pla gene was significantly (P <= .05)
      higher in strain C2944 than in strain CO92. Given pla's role in Y. pestis
      virulence, this difference may have important implications for the strain's
      virulence.

PMID- 21197444
TI  - Chronic cerebral ischaemia forms new cholinergic mechanisms of learning and
      memory.
AB  - The purpose of this research was a comparative analysis of cholinergic synaptic
      organization following learning and memory in normal and chronic cerebral
      ischaemic rats in the Morris water maze model. Choline acetyltransferase and
      protein content were determined in subpopulations of presynapses of "light" and
      "heavy" synaptosomal fractions of the cortex and the hippocampus, and the
      cholinergic projective and intrinsic systems of the brain structures were taken
      into consideration. We found a strong involvement of cholinergic systems, both
      projective and intrinsic, in all forms of cognition. Each form of cognition had
      an individual cholinergic molecular profile and the cholinergic synaptic
      compositions in the ischaemic rat brains differed significantly from normal ones.
      Our data demonstrated that under ischaemic conditions, instead of damaged
      connections new key synaptic relationships, which were stable against
      pathological influences and able to restore damaged cognitive functions, arose.
      The plasticity of neurochemical links in the individual organization of certain
      types of cognition gave a new input into brain pathology and can be used in the
      future for alternative corrections of vascular and other degenerative dementias.

PMID- 21197445
TI  - Systematic review of the effect of diet and exercise lifestyle interventions in
      the secondary prevention of coronary heart disease.
AB  - The effectiveness of lifestyle interventions within secondary prevention of
      coronary heart disease (CHD) remains unclear. This systematic review aimed to
      determine their effectiveness and included randomized controlled trials of
      lifestyle interventions, in primary care or community settings, with a minimum
      follow-up of three months, published since 1990. 21 trials with 10,799 patients
      were included; the interventions were multifactorial (10), educational (4),
      psychological (3), dietary (1), organisational (2), and exercise (1). The overall
      results for modifiable risk factors suggested improvements in dietary and
      exercise outcomes but no overall effect on smoking outcomes. In trials that
      examined mortality and morbidity, significant benefits were reported for total
      mortality (in 4 of 6 trials; overall risk ratio (RR) 0.75 (95% confidence
      intervals (CI) 0.65, 0.87)), cardiovascular mortality (3 of 8 trials; overall RR
      0.63 (95% CI 0.47, 0.84)), and nonfatal cardiac events (5 of 9 trials; overall RR
      0.68 (95% CI 0.55, 0.84)). The heterogeneity between trials and generally poor
      quality of trials make any concrete conclusions difficult. However, the
      beneficial effects observed in this review are encouraging and should stimulate
      further research.

PMID- 21197446
TI  - Mechanisms of amyloid-Beta Peptide uptake by neurons: the role of lipid rafts and
      lipid raft-associated proteins.
AB  - A hallmark pathological feature of Alzheimer's disease (AD) is the accumulation
      of extracellular plaques composed of the amyloid-beta (Abeta) peptide. Thus,
      classically experiments were designed to examine Abeta toxicities within the
      central nervous system (CNS) from the extracellular space. However, a significant
      amount of evidence now suggests that intraneuronal accumulation of Abeta is
      neurotoxic and may play an important role in the disease progression of AD. One
      of the means by which neurons accumulate intracellular Abeta is through uptake of
      extracellular Abeta peptides, and this process may be a potential link between
      Abeta generation, synaptic dysfunction, and AD pathology. Recent studies have
      found that neuronal internalization of Abeta involves lipid rafts and various
      lipid raft-associated receptor proteins. Uptake mechanisms independent of lipid
      rafts have also been implicated. The aim of this paper is to summarize these
      findings and discuss their significance in the pathogenesis of AD.

PMID- 21197448
TI  - Cotransplantation of adipose tissue-derived insulin-secreting mesenchymal stem
      cells and hematopoietic stem cells: a novel therapy for insulin-dependent
      diabetes mellitus.
AB  - Aims. Insulin dependent diabetes mellitus (IDDM) is believed to be an autoimmune
      disorder with disturbed glucose/insulin metabolism, requiring life-long insulin
      replacement therapy (IRT), 30% of patients develop end-organ failure. We present
      our experience of cotransplantation of adipose tissue derived insulin-secreting
      mesenchymal stem cells (IS-AD-MSC) and cultured bone marrow (CBM) as IRT for
      these patients. Methods. This was a prospective open-labeled clinical trial to
      test efficacy and safety of IS-AD-MSC+CBM co-transplantation to treat IDDM,
      approved by the institutional review board after informed consent in 11 (males :
      females: 7 : 4) patients with 1-24-year disease duration, in age group: 13-43
      years, on mean values of exogenous insulin requirement of 1.14 units/kg BW/day,
      glycosylated hemoglobin (Hb1Ac): 8.47%, and c-peptide levels: 0.1 ng/mL.
      Intraportal infusion of xenogeneic-free IS-AD-MSC from living donors, subjected
      to defined culture conditions and phenotypically differentiated to insulin
      secreting cells, with mean quantum: 1.5 mL, expressing Pax-6, Isl-1, and pdx-1,
      cell counts: 2.1 * 10(3)/MUL, CD45(-)/90(+)/73(+):40/30.1%, C-Peptide level:1.8
      ng/mL, and insulin level: 339.3  IU/mL with CBM mean quantum: 96.3 mL and cell
      counts: 28.1 * 10(3)/MUL, CD45(-)/34(+):0.62%, was carried out. Results. All were
      successfully transplanted without any untoward effect. Over mean followup of 23
      months, they had a decreased mean exogenous insulin requirement to 0.63
      units/kgBW/day, Hb1Ac to 7.39%, raised serum c-peptide levels to 0.38 ng/mL, and
      became free of diabetic ketoacidosis events with mean 2.5 Kg weight gain on
      normal vegetarian diet and physical activities. Conclusion. This is the first
      report of treating IDDM with insulin-secreting-AD-MSC+CBM safely and effectively
      with relatively simple techniques.

PMID- 21197447
TI  - Metabolic phenotype and adipose tissue inflammation in patients with chronic
      obstructive pulmonary disease.
AB  - Potential links between metabolic derangements and adipose tissue (AT)
      inflammation in patients with chronic obstructive pulmonary disease (COPD) are
      unexplored. We investigated AT expressions of interleukin (IL)-6, tumor necrosis
      factor (TNF)-alpha, CD68 (macrophage cell surface receptor), caspase-3, and Bax,
      and their relationships to the metabolic phenotype in nine cachectic, 12 normal
      weight, 12 overweight, and 11 obese patients with COPD (age 62.3 +/- 7.2 years).
      With increasing body mass index, increases in AT expressions of IL-6, TNF-alpha,
      and CD68 were observed (P < .001; P = .005; P < .001, resp.), in association with
      reduced insulin sensitivity (P < .001). No differences were observed between
      cachectic and normal-weight patients in AT expressions of inflammatory or
      proapoptotic markers. Adipose tissue CD68 and TNF-alpha expressions predicted
      insulin sensitivity independently of known confounders (P = .005; P = .025; R(2)
      = 0.840). Our results suggest that AT inflammation in obese COPD patients relates
      to insulin resistance. Cachectic patients remain insulin sensitive, with no AT
      upregulation of inflammatory or proapoptotic markers.

PMID- 21197449
TI  - Investigation of antiphosphatidyl-serine antibody and antiphosphatidyl-inositol
      antibody in ischemic stroke patients.
AB  - Antiphospholipid syndrome is characterized by arterial or venous thrombosis and
      the presence of antiphospholipid antibodies (aPL). We measured beta2-GPI aCL,
      IgGaCL, LA, antiphosphatidyl-serine antibody (PS), and antiphosphatidyl-inositol
      antibody (PI) in each patient at one month after the onset of stroke. In
      addition, carotid artery echography was performed in patients positive for PI or
      PS. Among the 250 patients, 13.6% (34/250) were positive for either PI or PS, and
      6.8% (17/250) were positive for both. Carotid artery echography performed on
      these 34 patients showed that the frequencies of increased intimal-medial
      thickness (IMT) of 1.1 mm or more, plaque, and carotid artery stenosis of 50% or
      more were all significantly higher in patients positive for antinuclear antibody
      than those negative for the antibody (P < .05). PI and PS are associated with
      antinuclear antibody and precipitation of atherosclerosis. Ischemic stroke
      patients with SLE frequently showed a variety of antiphospholipid-protein
      antibodies.

PMID- 21197450
TI  - Analysis of KRAS Mutations of Exon 2 Codons 12 and 13 by SNaPshot Analysis in
      Comparison to Common DNA Sequencing.
AB  - Due to the call for fast KRAS mutation status analysis for treatment of patients
      with monoclonal antibodies for metastatic colorectal cancer, sensitive, economic,
      and easily feasible methods are required. Under this aspect, the sensitivity and
      specificity of the SNaPshot analysis in comparison to the commonly used DNA
      sequencing was checked. We examined KRAS mutations in exon 2 codons 12 and 13
      with DNA sequencing and SNaPshot analysis in 100 formalin-fixed paraffin-embedded
      tumor tissue samples of pancreatic carcinoma, colorectal carcinoma, and nonsmall
      cell lung cancer specimens of the primary tumor or metastases. 40% of these
      samples demonstrated mutated KRAS genes using sequencing and SNaPshot-analysis;
      additional five samples (45/100) were identified only with the SNaPshot. KRAS
      mutation detection is feasible with the reliable SNaPshot analysis method. The
      more frequent mutation detection by the SNaPshot analysis shows that this method
      has a high probability of accuracy in the detection of KRAS mutations compared to
      sequencing.

PMID- 21197452
TI  - Controversies of treatment modalities for cerebral venous thrombosis.
AB  - Cerebral vein thrombosis has been well recognized for nearly two centuries.
      However, therapeutic options for the condition are limited due to lack of large
      randomized trials. The various modalities reportedly used include antiplatelets,
      anticoagulation, fibrinolysis, and mechanical thrombectomy. Of these,
      antiplatelets are the least studied, and there are only anecdotal reports of
      aspirin use. Anticoagulation is the most widely used and accepted modality with
      favorable outcomes documented in two randomized controlled trials. Various
      fibrinolytic agents have also been tried. Local infusions have shown more promise
      compared to systemic agents. Similarly, mechanical thrombectomy has been used to
      augment the effects of chemical thrombolysis. However, in the absence of
      randomized controlled trials; there is no concrete evidence of the safety and
      efficacy of either of these modalities. Limited study series disclosed that
      decompression surgery in malignant CVT can be life saving and provides good
      neurological outcome in some cases. Conclusion. Overall therapeutics for CVT need
      larger randomized controlled trials. Anticoagulaion with heparin is the only
      modality with a reasonable evidence to support its use in CVT. Endovascular
      thrombolysis and mechanical thrombectomy are reserved for selected cases who fail
      anticoagulation and decompression surgery for malignant CVT with impending
      herniation.

PMID- 21197451
TI  - Role of IL-17 and Th17 cells in liver diseases.
AB  - Unbalanced Th1/Th2 T-cell responses in the liver are a characteristic of hepatic
      inflammation and subsequent liver fibrosis. The recently discovered Th17 cells, a
      subtype of CD4(+) T-helper cells mainly producing IL-17 and IL-22, have initially
      been linked to host defense against infections and to autoimmunity. Their
      preferred differentiation upon TGFbeta and IL-6, two cytokines abundantly present
      in injured liver, makes a contribution of Th17 cells to hepatic inflammation very
      likely. Indeed, initial studies in humans revealed activated Th17 cells and Th17
      related cytokines in various liver diseases. However, functional experiments in
      mouse models are not fully conclusive at present, and the pathogenic contribution
      of Th17 cells to liver inflammation might vary upon the disease etiology, for
      example, between infectious and autoimmune disorders. Understanding the
      chemokines and chemokine receptors promoting hepatic Th17 cell recruitment
      (possibly CCR6 or CCR4) might reveal new therapeutic targets interfering with
      Th17 migration or differentiation in liver disease.

PMID- 21197453
TI  - Hepatitis C virus induces regulatory T cells by naturally occurring viral
      variants to suppress T cell responses.
AB  - Regulatory T cell markers are increased in chronically infected individuals with
      the hepatitis C virus (HCV), but to date, the induction and maintenance of Tregs
      in HCV infection has not been clearly defined. In this paper, we demonstrate that
      naturally occurring viral variants suppress T cell responses to cognate NS3(358
      375) in an antigen-specific manner. Of four archetypal variants, S370P induced
      regulatory T cell markers in comparison to NS3(358-375)-stimulated CD4 T cells.
      Further, the addition of variant-specific CD4 T cells back into a polyclonal
      culture in a dose-dependent manner inhibited the T cell response. These results
      suggest that HCV is able to induce antigen-specific regulatory T cells to
      suppress the antiviral T cell response in an antigen-specific manner, thus
      contributing to a niche within the host that could be conducive to HCV
      persistence.

PMID- 21197455
TI  - Sperm DNA integrity and meiotic behavior assessment in an infertile male carrier
      of a 9qh+++ polymorphism.
AB  - Although several reports on male infertility suggest a relationship between
      chromosome 9 polymorphisms and infertility, the effects on the phenotype have not
      been extensively reported. In this study, an infertile patient was found to carry
      a 9qh+++ chromosome. The flow cytometric TUNEL assay and SCD test have been
      applied to characterize sperm DNA integrity. In order to assess its meiotic
      behaviour, synapsis, recombination, and aneuploidy, analyses have been also
      performed. Sperm DNA fragmentation (SDF) was 77.81% and 87% for the TUNEL and SCD
      tests, respectively. Ninety-two percent of pachytene cells analyzed showed
      meiotic abnormalities. The mean number of MLH1 foci per pachytene in the control
      group was higher (49) than the mean found in the 9qh+++ patient (38) (P < .0001).
      In spermatozoa, significant increases of disomy rates were observed for
      chromosome 18 and for the sex chromosomes (P < .0001). These disturbances could
      be present in other male carriers of a less marked 9qh+.

PMID- 21197454
TI  - Regulating the regulators: the post-translational code of class I HDAC1 and
      HDAC2.
AB  - Class I histone deacetylases (HDACs) are cellular enzymes expressed in many
      tissues and play crucial roles in differentiation, proliferation, and cancer.
      HDAC1 and HDAC2 in particular are highly homologous proteins that show redundant
      or specific roles in different cell types or in response to different stimuli and
      signaling pathways. The molecular details of this dual regulation are largely
      unknown. HDAC1 and HDAC2 are not only protein modifiers, but are in turn
      regulated by post-translational modifications (PTMs): phosphorylation,
      acetylation, ubiquitination, SUMOylation, nitrosylation, and carbonylation. Some
      of these PTMs occur and crosstalk specifically on HDAC1 or HDAC2, creating a
      rational "code" for a differential, context-related regulation. The global
      comprehension of this PTM code is central for dissecting the role of single HDAC1
      and HDAC2 in physiology and pathology.

PMID- 21197456
TI  - Mutation of herpesvirus Saimiri ORF51 glycoprotein specifically targets
      infectivity to hepatocellular carcinoma cell lines.
AB  - Herpesvirus saimiri (HVS) is a gamma herpesvirus with several properties that
      make it an amenable gene therapy vector; namely its large packaging capacity, its
      ability to persist as a nonintegrated episome, and its ability to infect numerous
      human cell types. We used RecA-mediated recombination to develop an HVS vector
      with a mutated virion protein. The heparan sulphate-binding region of HVS ORF51
      was substituted for a peptide sequence which interacts with somatostatin
      receptors (SSTRs), overexpressed on hepatocellular carcinoma (HCC) cells. HVS
      mORF51 showed reduced infectivity in non-HCC human cell lines compared to wild
      type virus. Strikingly, HVS mORF51 retained its ability to infect HCC cell lines
      efficiently. However, neutralisation assays suggest that HVS mORF51 has no
      enhanced binding to SSTRs. Therefore, mutation of the ORF51 glycoprotein has
      specifically targeted HVS to HCC cell lines by reducing the infectivity of other
      cell types; however, the mechanism for this targeting is unknown.

PMID- 21197457
TI  - Clinical characteristics of tuberculosis-associated immune reconstitution
      inflammatory syndrome in North Indian population of HIV/AIDS patients receiving
      HAART.
AB  - BACKGROUND & OBJECTIVE: IRIS is an important complication that occurs during
      management of HIV-TB coinfection and it poses difficulty in diagnosis. Previous
      studies have reported variable incidence of IRIS. The present study was
      undertaken to describe the pattern of TB-associated IRIS using recently proposed
      consensus case-definitions for TB-IRIS for its use in resource-limited settings.
      METHODS: A prospective analysis of ART-naive adults started on HAART from
      November, 2008 to May, 2010 was done in a tertiary care hospital in north India.
      A total 224 patients divided into two groups, one with HIV-TB and the other with
      HIV alone, were followedup for a minimum period of 3 months. The diagnosis of TB
      was categorised as ''definitive" and ''probable". RESULTS: Out of a total of 224
      patients, 203 completed followup. Paradoxical TB-IRIS occurred in 5 of 123 (4%)
      HIV-TB patients while 6 of 80 (7.5%) HIV patients developed ART-associated TB. A
      reduction in plasma viral load was significantly (P = .016) associated with
      paradoxical TB-IRIS. No identifiable risk factors were associated with the
      development of ART-associated TB. CONCLUSION: The consensus case-definitions are
      useful tools in the diagnosis of TB-associated IRIS. High index of clinical
      suspicion is required for an early diagnosis.

PMID- 21197458
TI  - Physiologic Responses to Infrarenal Aortic Cross-Clamping during Laparoscopic or
      Conventional Vascular Surgery in Experimental Animal Model: Comparative Study.
AB  - The aim of this study was to compare the hemodynamic and ventilatory effects of
      prolonged infrarenal aortic cross-clamping in pigs undergoing either laparotomy
      or laparoscopy. 18 pigs were used for this study. Infrarenal aortic crossclamping
      was performed for 60 minutes in groups I (laparotomy, n = 6) and II (laparoscopy,
      n = 6). Group III (laparoscopy, n = 6) underwent a 120-minute long
      pneumoperitoneum in absence of aortic clamping (sham group). Ventilatory and
      hemodynamic parameters and renal function were serially determined in all groups.
      A significant decrease in pH and significant increase in PaCO(2) were observed in
      group II, whereas no changes in these parameters were seen in group I and III.
      All variables returned to values similar to baseline in groups I and II 60
      minutes after declamping. A significant increase in renal resistive index was
      evidenced during laparoscopy, with significantly higher values seen in Group II.
      Thus a synergic effect of pneumoperitoneum and aortic cross-clamping was seen in
      this study. These two factors together cause decreased renal perfusion and
      acidosis, thus negatively affecting the patient's general state during this type
      of surgery.

PMID- 21197459
TI  - Successful treatment of chronic mucocutaneous candidiasis caused by azole
      resistant Candida albicans with posaconazole.
AB  - Refractory or recurrent infections of skin, nails, and the mucous membranes are
      clinical signs of chronic mucocutaneous candidiasis, frequently associated with
      immunological defects. Here we describe a 39-years-old female patient, with
      familial CMC, that presented with an extensive infection caused by an azole
      resistant Candida albicans isolate, successfully treated with posaconazole.

PMID- 21197460
TI  - Diffeomorphic registration of images with variable contrast enhancement.
AB  - Nonrigid image registration is widely used to estimate tissue deformations in
      highly deformable anatomies. Among the existing methods, nonparametric
      registration algorithms such as optical flow, or Demons, usually have the
      advantage of being fast and easy to use. Recently, a diffeomorphic version of the
      Demons algorithm was proposed. This provides the advantage of producing
      invertible displacement fields, which is a necessary condition for these to be
      physical. However, such methods are based on the matching of intensities and are
      not suitable for registering images with different contrast enhancement. In such
      cases, a registration method based on the local phase like the Morphons has to be
      used. In this paper, a diffeomorphic version of the Morphons registration method
      is proposed and compared to conventional Morphons, Demons, and diffeomorphic
      Demons. The method is validated in the context of radiotherapy for lung cancer
      patients on several 4D respiratory-correlated CT scans of the thorax with and
      without variable contrast enhancement.

PMID- 21197461
TI  - Bilateral vallecular cysts as a cause of Dysphagia: case report and literature
      review.
AB  - Cysts of the vallecula are rare, accounting for 10.5% to 20.1% of all laryngeal
      cysts. Vallecular cysts may present with diverse symptoms affecting the voice,
      airway, and swallowing. We describe the evaluation and treatment of a 70-year-old
      woman who presented with dysphagia caused by large bilateral vallecular cysts.

PMID- 21197463
TI  - Parafibromin as a diagnostic instrument for parathyroid carcinoma-lone ranger or
      part of the posse?
AB  - The diagnosis of parathyroid carcinoma requires an invasive growth pattern or
      metastases detected at histopathological examination; unfortunately, not all
      carcinomas exhibit visible malignant properties at the initial assessment.
      Therefore, immunohistochemical markers have been sought for the recognition of
      parathyroid malignancy. In 2003, the Hyperparathyroidism 2 (HRPT2) gene was found
      mutated in the majority of sporadic parathyroid carcinomas investigated, and
      studies regarding the protein product parafibromin proposed loss of nuclear
      parafibromin as a highly sensitive marker for the detection of parathyroid
      carcinoma. Recent studies have not fully reproduced these findings, as subsets of
      carcinomas display positive parafibromin immunoreactivity, and fractions of
      adenomas demonstrate absent expression. Overall, parafibromin is a marker of
      value to the endocrine pathologist, but it cannot be recommended as a sole
      indicator of parathyroid carcinoma. Additional markers such as protein gene
      product 9.5 (PGP9.5) and adenomatous polyposis coli (APC) could complement
      parafibromin when assessing malignant potential of parathyroid tumours.

PMID- 21197462
TI  - Heterogeneity in multiple sclerosis: scratching the surface of a complex disease.
AB  - Multiple Sclerosis (MS) is the most common demyelinating disease of the central
      nervous system. Although the etiology and the pathogenesis of MS has been
      extensively investigated, no single pathway, reliable biomarker, diagnostic test,
      or specific treatment have yet been identified for all MS patients. One of the
      reasons behind this failure is likely to be the wide heterogeneity observed
      within the MS population. The clinical course of MS is highly variable and
      includes several subcategories and variants. Moreover, apart from the well
      established association with the HLA-class II DRB1*15:01 allele, other genetic
      variants have been shown to vary significantly across different populations and
      individuals. Finally both pathological and immunological studies suggest that
      different pathways may be active in different MS patients. We conclude that these
      "MS subtypes" should still be considered as part of the same disease but
      hypothesize that spatiotemporal effects of genetic and environmental agents
      differentially influence MS course. These considerations are extremely relevant,
      as outcome prediction and personalised medicine represent the central aim of
      modern research.

PMID- 21197466
TI  - Feeding Behavior-Related Toxicity due to Nandina domestica in Cedar Waxwings
      (Bombycilla cedrorum).
AB  - Dozens of Cedar Waxwings were found dead in Thomas County, Georgia, USA, in April
      2009. Five of these were examined grossly and microscopically. Grossly, all the
      examined birds had pulmonary, mediastinal, and tracheal hemorrhages.
      Microscopically, several tissues and organs were diffusely congested and
      hemorrhagic. Congestion and hemorrhage were marked in the lungs. Intact and
      partly digested berries of Nandina domestica Thunb. were the only ingesta found
      in the gastrointestinal tract of these birds. Due to their voracious feeding
      behavior, the birds had eaten toxic doses of N. domestica berries. N. domestica
      contains cyanide and is one of the few berries readily available at this time of
      the year in the region. The gross and microscopic findings are consistent with
      lesions associated with cyanide toxicity. This paper for the first time documents
      toxicity associated with N. domestica in Cedar Waxwings.

PMID- 21197464
TI  - Jun dimerization protein 2 controls senescence and differentiation via regulating
      histone modification.
AB  - Transcription factor, Jun dimerization protein 2 (JDP2), binds directly to
      histones and DNAs and then inhibits the p300-mediated acetylation both of core
      histones and of reconstituted nucleosomes that contain JDP2 recognition DNA
      sequences. JDP2 plays a key role as a repressor of adipocyte differentiation by
      regulation of the expression of the gene C/EBPdelta via inhibition of histone
      acetylation. Moreover, JDP2-deficient mouse embryonic fibroblasts (JDP2(-/-)
      MEFs) are resistant to replicative senescence. JDP2 inhibits the recruitment of
      polycomb repressive complexes (PRC1 and PRC2) to the promoter of the gene
      encoding p16(Ink4a), resulting from the inhibition of methylation of lysine 27 of
      histone H3 (H3K27). Therefore, it seems that chromatin-remodeling factors,
      including the PRC complex controlled by JDP2, may be important players in the
      senescence program. The novel mechanisms that underline the action of JDP2 in
      inducing cellular senescence and suppressing adipocyte differentiation are
      reviewed.

PMID- 21197465
TI  - The Role of RUNX2 in Osteosarcoma Oncogenesis.
AB  - Osteosarcoma is an aggressive but ill-understood cancer of bone that
      predominantly affects adolescents. Its rarity and biological heterogeneity have
      limited studies of its molecular basis. In recent years, an important role has
      emerged for the RUNX2 "platform protein" in osteosarcoma oncogenesis. RUNX
      proteins are DNA-binding transcription factors that regulate the expression of
      multiple genes involved in cellular differentiation and cell-cycle progression.
      RUNX2 is genetically essential for developing bone and osteoblast maturation.
      Studies of osteosarcoma tumours have revealed that the RUNX2 DNA copy number
      together with RNA and protein levels are highly elevated in osteosarcoma tumors.
      The protein is also important for metastatic bone disease of prostate and breast
      cancers, while RUNX2 may have both tumor suppressive and oncogenic roles in bone
      morphogenesis. This paper provides a synopsis of the current understanding of the
      functions of RUNX2 and its potential role in osteosarcoma and suggests directions
      for future study.

PMID- 21197467
TI  - Evaluation of itch by using NC/NgaTnd mice: a model of human atopic dermatitis.
AB  - Atopic dermatitis (AD) is the extremely complicated syndrome that various
      abnormalities develop in a heap. There are various factors in patients for the
      onset and exacerbation of AD, including genetic cofactors of individuals,
      environmental factors, the failure of the skin barrier function, unfavorable
      regulation of the immune system, and the hypersensitivity of sensory nerves. In
      recent years, there have been many trials of the drug discovery that targets
      itch, because itch is one of the most serious clinical symptoms of AD. The
      selection of the suitable animal model that represents the condition of patients,
      as well as innovative analyzing protocols that can precisely evaluate itch, is
      indispensable for investigation of an effective drug for AD. In the paper, the
      unique spontaneous animal model for AD (NC/NgaTnd mice) and the novel
      quantification system of the laboratory animals that may bring a great progress
      in the future study of itch are outlined.

PMID- 21197468
TI  - Targeting angiogenesis in childhood sarcomas.
AB  - Angiogenesis and vasculogenesis constitute two processes in the formation of new
      blood vessels and are essential for progression of solid tumors. Consequently,
      targeting angiogenesis, and to a lesser extent vasculogenesis, has become a major
      focus in cancer drug development. Angiogenesis inhibitors are now being tested in
      pediatric populations whereas inhibitors of vasculogenesis are in an earlier
      stage of development. Despite the initial enthusiasm for targeting angiogenesis
      for treatment of cancer, clinical trials have shown only incremental increases in
      survival, and agents have been largely cytostatic rather than inducing tumor
      regressions. Consequently, the role of such therapeutic approaches in the context
      of curative intent for childhood sarcomas is less clear. Here we review the
      literature on blood vessel formation in sarcomas with a focus on pediatric
      sarcomas and developments in targeting angiogenesis for treatment of these rare
      cancers.

PMID- 21197469
TI  - Loss of function of e-cadherin in embryonic stem cells and the relevance to
      models of tumorigenesis.
AB  - E-cadherin is the primary cell adhesion molecule within the epithelium, and loss
      of this protein is associated with a more aggressive tumour phenotype and poorer
      patient prognosis in many cancers. Loss of E-cadherin is a defining
      characteristic of epithelial-mesenchymal transition (EMT), a process associated
      with tumour cell metastasis. We have previously demonstrated an EMT event during
      embryonic stem (ES) cell differentiation, and that loss of E-cadherin in these
      cells results in altered growth factor response and changes in cell surface
      localisation of promigratory molecules. We discuss the implication of loss of E
      cadherin in ES cells within the context of cancer stem cells and current models
      of tumorigenesis. We propose that aberrant E-cadherin expression is a critical
      contributing factor to neoplasia and the early stages of tumorigenesis in the
      absence of EMT by altering growth factor response of the cells, resulting in
      increased proliferation, decreased apoptosis, and acquisition of a stem cell-like
      phenotype.

PMID- 21197470
TI  - The migraine-ischemic stroke relation in young adults.
AB  - In spite of the strong epidemiologic evidence linking migraine and ischemic
      stroke in young adults, the mechanisms explaining this association remain poorly
      understood. The observation that stroke occurs more frequently during the
      interictal phase of migraine prompts to speculation that an indirect relation
      between the two diseases might exist. In this regard, four major issues might be
      considered which may be summarized as follows: (1) the migraine-ischemic stroke
      relation is influenced by specific risk factors such as patent foramen ovale or
      endothelial dysfunction and more frequent in particular conditions like
      spontaneous cervical artery dissection; (2) migraine is associated with an
      increased prevalence of cardiovascular risk factors; (3) the link is caused by
      migraine-specific drugs; (4) migraine and ischemic vascular events are linked via
      a genetic component. In the present paper, we will review epidemiological
      studies, discuss potential mechanisms of migraine-induced stroke and comorbid
      ischemic stroke, and pose new research questions.

PMID- 21197471
TI  - Targeting the p53 Pathway in Ewing Sarcoma.
AB  - The p53 tumour suppressor plays a pivotal role in the prevention of oncogenic
      transformation. Cancers frequently evade the potent antitumour surveillance
      mechanisms of p53 through mutation of the TP53 gene, with approximately 50% of
      all human malignancies expressing dysfunctional, mutated p53 proteins.
      Interestingly, genetic lesions in the TP53 gene are only observed in 10% of Ewing
      Sarcomas, with the majority of these sarcomas expressing a functional wild-type
      p53. In addition, the p53 downstream signaling pathways and DNA-damage cell cycle
      checkpoints remain functionally intact in these sarcomas. This paper summarizes
      recent insights into the functional capabilities and regulation of p53 in Ewing
      Sarcoma, with a particular focus on the cross-talk between p53 and the EWS-FLI1
      gene rearrangement frequently associated with this disease. The development of
      several activators of p53 is discussed, with recent evidence demonstrating the
      potential of small molecule p53 activators as a promising systemic therapeutic
      approach for the treatment of Ewing Sarcomas with wild-type p53.

PMID- 21197472
TI  - Bacterial artificial chromosome mutagenesis using recombineering.
AB  - Gene expression from bacterial artificial chromosome (BAC) clones has been
      demonstrated to facilitate physiologically relevant levels compared to viral and
      nonviral cDNA vectors. BACs are large enough to transfer intact genes in their
      native chromosomal setting together with flanking regulatory elements to provide
      all the signals for correct spatiotemporal gene expression. Until recently, the
      use of BACs for functional studies has been limited because their large size has
      inherently presented a major obstacle for introducing modifications using
      conventional genetic engineering strategies. The development of in vivo
      homologous recombination strategies based on recombineering in E. coli has helped
      resolve this problem by enabling facile engineering of high molecular weight BAC
      DNA without dependence on suitably placed restriction enzymes or cloning steps.
      These techniques have considerably expanded the possibilities for studying
      functional genetics using BACs in vitro and in vivo.

PMID- 21197474
TI  - Construction and characterization of an infectious murine gammaherpesivrus-68
      bacterial artificial chromosome.
AB  - Here we describe the cloning of a sequenced WUMS isolate of murine
      gammaherpesvirus-68 (MHV-68, gammaHV-68, also known as MuHV-4) as a bacterial
      artificial chromosome (BAC). We engineered the insertion of the BAC sequence
      flanked by loxP sites into the left end of the viral genome before the M1 open
      reading frame. The infectious viruses were reconstituted following transfection
      of the MHV-68 BAC DNA into cells. The MHV-68 BAC-derived virus replicated
      indistinguishably from the wild-type virus in cultured cells. Excision of the BAC
      insert was efficiently achieved by coexpressing the Cre recombinase. Although the
      BAC insertion did not significantly affect acute productive infection in the
      lung, it severely compromised the ability of MHV-68 to establish splenic latency.
      Removal of the BAC sequence restored the wild-type level of latency. Site
      specific mutagenesis was carried out by RecA-mediated recombination to
      demonstrate that this infectious BAC clone can be used for genetic studies of MHV
      68.

PMID- 21197473
TI  - Dr. Jekyll and Mr. Hyde: The Two Faces of the FUS/EWS/TAF15 Protein Family.
AB  - FUS, EWS, and TAF15 form the FET family of RNA-binding proteins whose genes are
      found rearranged with various transcription factor genes predominantly in
      sarcomas and in rare hematopoietic and epithelial cancers. The resulting fusion
      gene products have attracted considerable interest as diagnostic and promising
      therapeutic targets. So far, oncogenic FET fusion proteins have been regarded as
      strong transcription factors that aberrantly activate or repress target genes of
      their DNA-binding fusion partners. However, the role of the transactivating
      domain in the context of the normal FET proteins is poorly defined, and,
      therefore, our knowledge on how FET aberrations impact on tumor biology is
      incomplete. Since we believe that a full understanding of aberrant FET protein
      function can only arise from looking at both sides of the coin, the good and the
      evil, this paper summarizes evidence for the central function of FET proteins in
      bridging RNA transcription, processing, transport, and DNA repair.

PMID- 21197475
TI  - Prone Positioning and Intravenous Zanamivir may Represent Effective Alternatives
      for Patients with Severe ARDS Virus A (H1N1) Related Pneumonia in Hospitals with
      no Access to ECMO.
AB  - The first patient with influenza A/H1N1-related pneumonia was admitted to an
      Italian ICU at the end of August 2009. Until then, despite the international
      alarm, the level of awareness was low and very few Italian hospitals were
      equipped with ECMOs. Moreover the PCR test for A H1N1 virus was sporadically
      available and the emergency departments of even the largest institutions could
      rely only on the rapid test for the urgent screening of patients with pneumonia
      and respiratory failure. On September 5th, a young and "apparently" previously
      healthy man, was admitted to our ICU because of a severe ARDS caused by influenza
      A H1N1 virus. As there was no ECMO available, he was treated with prolonged
      cycles of prone positioning ventilation. Antiviral treatment was started with
      Oseltamivir, but as enteral absorption was impaired by paralytic ileus and tube
      feeding intolerance, Oseltamivir had to be discontinued. Intravenous Zanamivir
      1200 mg/day for ten days was therefore prescribed as "off label" antiviral
      therapy. A bone marrow biopsy allowed the diagnosis of an initial stage of "hairy
      cells leukaemia." ARDS related to A/H1N1 influenza was the first sign of the
      disease in our patient. He did well with complete clearance of the infection from
      the BAL after 10 days of Zanamivir, although the nasopharyngeal swabs remained
      positive for ten more days. Prone positioning ventilation may be a life-saver
      strategy in patients with severe ARDS when ECMO is not immediately available.
      However, prone positioning ventilation is often associated with severe impairment
      of the absorption of drugs that require enteral administration via the
      nasogastric tube. In these cases, intravenous Zanamivir may be an effective
      alternative strategy.

PMID- 21197477
TI  - Incidence patterns and outcomes for hodgkin lymphoma patients in the United
      States.
AB  - Hodgkin lymphoma (HL) demonstrates heterogenous histologic findings, clinical
      presentation, and outcomes. Using the United States Surveillance, Epidemiology,
      and End Results (SEER) data we examined relationships between patient
      characteristics, clinical features at diagnosis, and survival in HL patients.
      From 2000 to 2007, 16,710 cases were recorded in 17 SEER registries. Blacks and
      Asians had low incidence (black/white incidence rate ratio (IRR) 0.86, P < .01;
      Asian/white IRR 0.43, P < .01). The bimodal pattern of incidence was less
      prominent for black males. Asians and Blacks presented at a mean age of 38 years
      compared to 42 years for Whites (P < .001). Race was a predictor for survival
      with HR of 1.19 (95% CI 1.11-1.28) for Blacks. Age was the most important
      predictor of survival (HR for patients >=45 years 5.08, 95% CI 4.86-5.31). These
      current patterns for presentation and outcomes of HL help to delineate key
      populations in order to explore risk factors for HL and strategies to improve
      treatment outcomes.

PMID- 21197476
TI  - ER Stress and Iron Homeostasis: A New Frontier for the UPR.
AB  - The C282Y mutation of HFE accounts for the majority of cases of the iron overload
      disease Hereditary Hemochromatosis (HH). The conformational changes introduced by
      this mutation impair the HFE association with beta(2)-microglobulin (beta(2)m)
      and the cell surface expression of the protein: with two major consequences. From
      a functional perspective, the ability of HFE to bind to transferrin receptors 1
      and 2 is lost in the C282Y mutant, thus affecting hepcidin regulation. Also due
      to the faulty assembly with beta(2)m, HFE-C282Y molecules remain in the
      endoplasmic reticulum (ER) as aggregates that undergo proteasomal degradation and
      activate an Unfolded Protein Response (UPR). UPR activation, regardless of the ER
      stress stimuli, was shown to reshape the expression profile of iron-related genes
      and to decrease MHC-I cell surface expression. The possibility of a HFE-C282Y
      mediated interplay between the UPR and iron homeostasis influencing disease
      progression and the clinical heterogeneity among C282Y carriers is discussed. The
      responsiveness of the ER chaperone calreticulin to both ER and iron-induced
      oxidative stresses, and its correlation with HH patients' phenotype, reinforce
      the interest of dissecting the UPR signaling/iron metabolism crosstalk and points
      to the potential clinical value of use of pharmacological chaperones in HFE-HH.

PMID- 21197478
TI  - A signal processing method to explore similarity in protein flexibility.
AB  - Understanding mechanisms of protein flexibility is of great importance to
      structural biology. The ability to detect similarities between proteins and their
      patterns is vital in discovering new information about unknown protein functions.
      A Distance Constraint Model (DCM) provides a means to generate a variety of
      flexibility measures based on a given protein structure. Although information
      about mechanical properties of flexibility is critical for understanding protein
      function for a given protein, the question of whether certain characteristics are
      shared across homologous proteins is difficult to assess. For a proper
      assessment, a quantified measure of similarity is necessary. This paper begins to
      explore image processing techniques to quantify similarities in signals and
      images that characterize protein flexibility. The dataset considered here
      consists of three different families of proteins, with three proteins in each
      family. The similarities and differences found within flexibility measures across
      homologous proteins do not align with sequence-based evolutionary methods.

PMID- 21197479
TI  - Special needs to prescribe exercise intensity for scientific studies.
AB  - There is clear evidence regarding the health benefits of physical activity. These
      benefits follow a dose-response relationship with a particular respect to
      exercise intensity. Guidelines for exercise testing and prescription have been
      established to provide optimal standards for exercise training. A wide range of
      intensities is used to prescribe exercise, but this approach is limited. Usually
      percentages of maximal oxygen uptake (VO(2)) or heart rate (HR) are applied to
      set exercise training intensity but this approach yields substantially variable
      metabolic and cardiocirculatory responses. Heterogeneous acute responses and
      training effects are explained by the nonuniform heart rate performance curve
      during incremental exercise which significantly alters the calculations of
      %HR(max) and %HRR target HR data. Similar limitations hold true for using
      %VO(2max) and %VO(2)R. The solution of these shortcomings is to strictly apply
      objective submaximal markers such as thresholds or turn points and to tailor
      exercise training within defined regions.

PMID- 21197480
TI  - Perfusion Imaging with SPECT in the Era of Pathophysiology-Based Biomarkers for
      Alzheimer's Disease.
AB  - SPECT allows registration of regional cerebral blood flow (rCBF) which is altered
      in a characteristic temporoparietal pattern in Alzheimer's Dementia. Numerous
      studies have shown the diagnostic value of reduced cerebral blood flow and
      metabolic changes using perfusion SPECT and FDG-PEPT in AD diagnosis as well as
      in differential diagnosis against frontotemporal dementia, dementia with Lewy
      bodies and vascular disease. Recently more pathophysiology-based biomarkers in
      CSF and Amyloid-PET tracers have been developed that probably have a higher
      diagnostic accuracy than the more indirect rCBF changes seen in perfusion SPECT.
      In the paper review, we describe recent advances in AD biomarkers as well as
      improvements in the SPECT technique.

PMID- 21197481
TI  - Pancreatic resections for advanced M1-pancreatic carcinoma: the value of
      synchronous metastasectomy.
AB  - BACKGROUND: For M1 pancreatic adenocarcinomas pancreatic resection is usually not
      indicated. However, in highly selected patients synchronous metastasectomy may be
      appropriate together with pancreatic resection when operative morbidity is low.
      MATERIALS AND METHODS: From January 1, 2004 to December, 2007 a total of 20
      patients with pancreatic malignancies were retrospectively evaluated who
      underwent pancreatic surgery with synchronous resection of hepatic, adjacent
      organ, or peritoneal metastases for proven UICC stage IV periampullary cancer of
      the pancreas. Perioperative as well as clinicopathological parameters were
      evaluated. RESULTS: There were 20 patients (9 men, 11 women; mean age 58 years)
      identified. The primary tumor was located in the pancreatic head (n = 9, 45%), in
      pancreatic tail (n = 9, 45%), and in the papilla Vateri (n = 2, 10%). Metastases
      were located in the liver (n = 14, 70%), peritoneum (n = 5, 25%), and omentum
      majus (n = 2, 10%). Lymphnode metastases were present in 16 patients (80%). All
      patients received resection of their tumors together with metastasectomy. Pylorus
      preserving duodenopancreatectomy was performed in 8 patients, distal
      pancreatectomy in 8, duodenopancreatectomy in 2, and total pancreatectomy in 2.
      Morbidity was 45% and there was no perioperative mortality. Median postoperative
      survival was 10.7 months (2.6-37.7 months) which was not significantly different
      from a matched-pair group of patients who underwent pancreatic resection for UICC
      adenocarcinoma of the pancreas (median survival 15.6 months; P = .1). CONCLUSION:
      Pancreatic resection for M1 periampullary cancer of the pancreas can be performed
      safely in well-selected patients. However, indication for surgery has to be made
      on an individual basis.

PMID- 21197484
TI  - Morphometric analysis of mandibular trabecular bone using cone beam computed
      tomography: an in vitro study.
AB  - PURPOSE: Recently, cone beam computed tomography (CBCT) was developed and applied
      to presurgical imaging for dental implant treatment. Because the values obtained
      from CBCT images are not absolute values, unlike the Hounsfield units obtained by
      medical CT, the relationship between the values of trabecular bone morphometry
      obtained in small-volume CBCT images and CT values obtained from multislice CT
      was evaluated in an in vitro study. MATERIALS AND METHODS: Small-volume CBCT and
      multislice CT were performed in the posterior mandible. Subsequently,
      morphometric analysis of the trabecular bone in CBCT images was performed using
      three-dimensional bone morphometry software, and the correlations between the
      trabecular bone volume per total tissue volume (BV/TV) obtained using CBCT images
      and CT values generated from multislice CT images were analyzed. RESULTS: BV/TV
      ranged from 3.1% to 42.7%, with a mean of 20.4% (SD: 11.4) when the setting was
      0.5 for the threshold. The correlations between BV/TV using the threshold values
      ranged from 0.3 to 0.7, and CT values showed a high level of correlation (range:
      0.83 to 0.93). CONCLUSIONS: The trabecular BV/TV was closely correlated with CT
      values obtained using multislice CT images. It was suggested that the trabecular
      BV/TV can be used to evaluate the density of mandibular cancellous bone in dental
      implant treatment.

PMID- 21197482
TI  - Multiple sclerosis: are protective immune mechanisms compromised by a complex
      infectious background?
AB  - The immunological background of multiple sclerosis (MS) manifests as an altered
      reactivity against a diverse range of infections, particularly with the Epstein
      Barr virus. Although this could be only an epiphenomenon of a more generalised
      dysfunction of the immune system in MS, it is also possible that a complex
      infectious background forms the basis of a specific immune dysregulation finally
      causing the disease. It is thus suggested that the complex infectious background
      bears the key for an understanding of the immune pathogenesis of the disease. It
      appears probable that improved standards of hygiene cause regulatory defects in
      the immune system, allowing the abnormal expression of human endogenous
      retroviral (HERV) genes. On the basis of epidemiological observations we describe
      how a failure of expansion or an eclipse of a subfraction of self-antigen
      specific CD8(+) T cells mediating immune repair, and a deleterious mode of action
      of HERV gene products, could underlie the pathogenesis of MS.

PMID- 21197483
TI  - Changes in stability after healing of immediately loaded dental implants.
AB  - PURPOSE: To investigate the parameters that affect primary stability of dental
      implants, to determine how primary stability influences posthealing stability,
      and to ascertain the effect of primary stability and insertion parameters on
      marginal bone loss. MATERIALS AND METHODS: A total of 940 immediately loaded
      implants were considered. Using resonance frequency analysis, primary stability
      (primary implant stability quotient [pISQ]) and stability after 4 months (tISQ)
      were recorded. When the differences between pISQ and tISQ exceeded 5 units,
      marginal bone loss was measured. The implants were placed into three groups based
      on their primary stability: high (pISQ > 72), moderate, and low (pISQ < 68).
      Changes in stability after 4 months of loading were evaluated. The relationships
      between pISQ, insertion parameters, DISQ (ie, tISQ - pISQ), and marginal bone
      loss were analyzed. The Student t test, one-way analysis of variance, and
      Spearman nonparametric correlation coefficient were employed for statistical
      evaluation. RESULTS: Of the 940 implants, tISQ was recorded in 526 implants and
      marginal bone loss was measured in 76 implants. There was no statistical
      relationship between pISQ and insertion torque. Primary stability was influenced
      by implant diameter but not by implant length. There was a significant
      relationship between implant insertion torque and bone type. The low primary
      stability group showed a significant increase in stability during healing.
      However, high primary stability implants demonstrated a significant reduction in
      their stability. The linear regression analysis demonstrated that at a pISQ of
      69.2, tISQ value would equal pISQ value. Correlations between marginal bone loss
      and final insertion torque and between marginal bone loss and DISQ values were
      observed. CONCLUSIONS: Stability of immediately loaded implants with high pISQ
      decreased significantly during the initial 4 months of healing. However,
      stability of implants with low primary stability increased significantly. DISQ
      and insertion torque showed correlation with marginal bone loss.

PMID- 21197485
TI  - Cell behavior related to implant surfaces with different microstructure and
      chemical composition: an in vitro analysis.
AB  - PURPOSE: This paper reports on an in vitro comparison of osteoblast and
      mesenchymal stem cell (MSC) adhesion, proliferation, and differentiation related
      to two different surface treatments applied to the same implant design to
      determine whether the interaction between cells and implants is influenced by
      surface structure and chemical composition of the implants. MATERIALS AND
      METHODS: Thirty-nine implants with a sandblasted (SB) surface and 39 implants
      with a grit-blasted and high-temperature acid-etched (GBAE) surface were used.
      The implant macrostructures and microstructures were analyzed by high- and low
      voltage scanning electron microscopy (SEM) and by stereo-SEM. The surface
      chemical composition was investigated by energy dispersive analysis and x-ray
      photoemission spectroscopy. SaOS-2 osteoblasts and human MSCs were used for the
      evaluation of cell proliferation and alkaline phosphatase enzymatic activity in
      contact with the two surfaces. RESULTS: The GBAE surface showed fewer
      contaminants and a very high percentage of titanium (19.7%) compared to the SB
      surface (14.2%). The two surfaces showed similar mean roughness (Ra), but the
      depth (Rz) and density (RSm) of the porosity were significantly increased in the
      GBAE surface. The GBAE surface presented more osteoblast and MSC proliferation
      than the SB surface. No statistically significant differences in alkaline
      phosphatase activity were found between surfaces for either cellular line.
      CONCLUSIONS: The GBAE surface showed less surface contaminants and a higher
      percentage of titanium (19.7%) than the SB surface. The macro/micropore
      structured design and chemical composition of the GBAE surface allowed greater
      cell adhesion and proliferation and an earlier cell spreading but did not play an
      obvious role in in vitro cellular differentiation.

PMID- 21197486
TI  - Finite element stress analysis of edentulous mandibles with different bone types
      supporting multiple-implant superstructures.
AB  - PURPOSE: The purpose of this study was to evaluate the influence of different
      types of bone on the stress distribution in the mandibular bone supporting a
      prefabricated bar-type implant prosthesis using three-dimensional finite element
      analysis. MATERIALS AND METHODS: Four finite element models (M) of a completely
      edentulous mandibular arch were built. The bone types varied from type 1 to type
      4 (M1, M2, M3, M4). The arch was restored using a prefabricated bar system
      supported by four interforaminal implants for the protocol prosthesis. Computer
      software was used to determine the stress fields. Three unilateral posterior
      loads (L) of 150 N were exerted on the prosthesis: L1, perpendicular to the
      prefabricated bar; L2, oblique (30 degrees) in the buccolingual direction; and
      L3, oblique (30 degrees) in the linguobuccal direction. The maximum principal
      stress (Omax) and the maximum principal strain (Emax) were obtained for cortical
      and trabecular bone. RESULTS: Types 3 and 4 bone showed the highest smax (MPa) in
      the cortical bone (19.9 and 18.2 for L1, 34.6 and 31.3 for L2, and 3.88 and 24.4
      for L3, respectively). The maximum principal strain (Emax) was observed in type 4
      cortical bone for all loads (1.80 for L1, 2.4 for L2, and 2.36 for L3).
      CONCLUSIONS: The cortical bone in M3 and M4 showed the highest stress
      concentration in the axial and buccolingual loading conditions. Bone types 1 and
      2 showed the lowest stress concentrations. For the linguobuccal loading
      condition, the cortical bone in M4 showed the highest stress concentration,
      followed by bone types 3, 2, and 1. Cortical bone in M4 showed the highest strain
      for all loading conditions. The bone type might not be the only decisive factor
      to influence the stress distribution the bone supporting an implant prosthesis
      anchored by a prefabricated bar.

PMID- 21197487
TI  - Accuracy of four transfer impression techniques for dental implants: a scanning
      electron microscopic analysis.
AB  - PURPOSE: The aim of this study was to evaluate, using scanning electron
      microscopy (SEM), the accuracy of four impression techniques for osseointegrated
      implants (with or without acrylic resin splinting and with irreversible
      hydrocolloid or polyvinyl siloxane [PVS] impression material). MATERIALS AND
      METHODS: A metal master model was made with three implant analogs and two
      prosthetic spaces. This model was used as the standard for all impressions. Two
      impression materials were used (irreversible hydrocolloid and PVS) and two
      transfer techniques were used (squared impression copings indexed by the
      impression material and squared impression copings splinted with acrylic resin).
      Four groups were therefore analyzed (n = 5): IH = irreversible hydrocolloid only,
      IHS = irreversible hydrocolloid + splint, P = PVS only, and PS = PVS + splint. A
      reference framework made with palladium-silver alloy over the UCLA abutment was
      created on the master model. The fit of this structure to the master model was
      used as a reference. SEM images of the front and side gaps between the abutments
      and the implant analogs were created and then measured using image analysis
      software. RESULTS: IH presented the largest misfit. The splinted impression
      copings generated a smaller marginal gap than the indexed material technique,
      irrespective of the impression material used. There was no significant difference
      between IHS, P, PS, and the reference (multivariate test, Wilks criteria).
      However, PS presented a standard deviation that was three times lower than those
      of the other groups, and its mean was closer to the reference. CONCLUSIONS: The
      IH impression technique was the least accurate technique. There was no difference
      between IHS, P, and PS techniques with regard to the reference constant. The
      impression techniques that used splinted impression copings generated more
      accurate casts, irrespective of the impression material.

PMID- 21197488
TI  - Effect of severe dietary magnesium deficiency on systemic bone density and
      removal torque of osseointegrated implants.
AB  - PURPOSE: This study evaluated the effect of severe magnesium (Mg) dietary
      deficiency on systemic bone density and biomechanical resistance of bone tissue
      to the removal torque of osseointegrated implants. MATERIALS AND METHODS: The
      sample consisted of 45 rats; each received a titanium implant in their tibial
      metaphysis. After 60 days, the animals were divided into three groups (n = 15)
      according to their dietary Mg: the control group received the recommended content
      of Mg, group Mg1 received a 75% reduction in dietary Mg content, and group Mg2
      was fed a diet with a 90% reduction in Mg content. Animals were sacrificed 150
      days after implant placement. Serum concentrations of Mg were measured and the
      effect of Mg deficiency on systemic bone density was evaluated by densitometry of
      the lumbar vertebrae and femur. Biomechanical characteristics were measured by
      resistance of the bone tissue to removal of the implants. RESULTS: Lower Mg serum
      concentrations were found for the Mg1 and Mg2 groups; however, densitometric
      analysis and torque evaluations showed a statistically significant difference
      only in the Mg2 group (P < .05). There was a statistically significant difference
      in removal torque between the Mg2 group and the control group. CONCLUSIONS: This
      study showed that a severe deficiency of Mg decreased the systemic bone density
      and removal torque of osseointegrated implants.

PMID- 21197489
TI  - Heat production during prosthetic preparation of a one-piece dental implant.
AB  - PURPOSE: Preparation of a one-piece dental implant abutment is often needed to
      achieve a proper emergence profile for a definitive restoration. However, this
      procedure may compromise osseointegration through the production of heat. The aim
      of this study was to measure heat production during implant abutment preparation
      with different volumes of water irrigation using a one-piece implant system.
      MATERIALS AND METHODS: Forty-five one-piece dental implants were used in this
      study. The implants were divided into three groups according to the water flow
      rate used during abutment preparation: 30 mL/min (G30), 15 mL/min (G15), and
      without water irrigation (G0). Thermocouples were positioned at the most coronal
      and most apical threads. The abutments were prepared using a high-speed dental
      handpiece. Preparation continued for 120 seconds or until the implant temperature
      reached 47 degrees C. RESULTS: The time needed to reach 47 degrees C in the most
      coronal thread of group G0 was 5.73 +/- 1.16 seconds. After the preparation was
      stopped at 47 degrees C, the temperature continued to increase until reaching a
      maximum temperature. None of the implants in the water irrigation groups reached
      47 degrees C. The time needed to reach maximum temperature was significantly
      shorter for group G0 than the groups with water irrigation. A strong positive
      correlation was found between coronal and apical recordings. CONCLUSION:
      Prosthetic preparation of one-piece dental implants without irrigation induced a
      rapid increase in temperature. Water irrigation reduced heat production during
      abutment preparation in a dose-dependent manner.

PMID- 21197490
TI  - Effect of splinting mini-implants on marginal bone loss: a biomechanical model
      and clinical randomized study with mandibular overdentures.
AB  - PURPOSE: This aim of this study was to evaluate the effect of splinting mini
      implants on marginal bone loss when used to retain mandibular overdentures.
      MATERIALS AND METHODS: With mathematical models, a finite element analysis was
      performed to compare the bone stress distribution around two mini-implants,
      either splinted with a bar superstructure or not splinted. In the clinical
      portion of this study, 90 mini-implants were placed in the anterior mandibles of
      45 completely edentulous patients selected from a public health center. Patients
      were randomly allocated into two groups. Group-ball (22 patients, n = 44)
      received two single ball-type mini-implants, and group-bar (23 patients, n = 46)
      received two mini-implants splinted with a prefabricated bar. All implants were
      placed using a flapless technique and loaded immediately. Marginal bone loss was
      assessed through standardized retroalveolar radiographs of each mini-implant and
      compared 5, 10, 15, and 24 months after implant placement. RESULTS: The finite
      element analysis showed the highest minimum principal stress (-118 MPa) in bone
      surrounding the unsplinted mini-implant, while around the splinted implants the
      principal stresses were -56.8 MPa. After 2 years of follow-up in the clinical
      study, group-ball showed a trend toward greater marginal bone loss than group-bar
      (1.43 +/- 1.26 mm and 0.92 +/- 0.75 mm, respectively). Group-ball showed a
      significantly higher prevalence of vertical bone loss than group-bar (chi-square
      test, two-tailed). CONCLUSION: Splinted mini-implants with a rigid superstructure
      decrease the bone stress level in comparison with single mini-implants. The
      effects of bone stress magnitude may explain the clinical outcome, in which
      splinted mini-implants supporting a mandibular overdenture showed less marginal
      bone loss compared with nonsplinted mini-implants. Vertical bone resorption
      morphology was significantly more prevalent in the latter group.

PMID- 21197491
TI  - Effects of a cementing technique in addition to luting agent on the uniaxial
      retention force of a single-tooth implant-supported restoration: an in vitro
      study.
AB  - PURPOSE: Excess residual cement around the implant margin has been shown to be
      detrimental to the peri-implant tissue. This in vitro study examines the
      retentive strengths of two different cementing techniques and two different
      luting agents on a machined titanium abutment and solid screw implants. The
      amount of reduction of excess cement weight between the two cementation
      techniques was assessed. MATERIALS AND METHODS: Forty gold castings were
      fabricated for 4.1 mm in diameter and 10 mm in length solid-screw dental implants
      paired with 5.5-mm machined titanium abutments. Twenty implants received a
      provisional cement, and 20 implants received a definitive cement. Each group was
      further divided into two groups. In the control group, cement was applied and the
      castings seated over the implant-abutment assembly. The excess cement was then
      removed. In the study group, a "practice abutment" was used to express excess
      cement prior to cementation. The weight of the implant-casting assembly was
      measured and the residual weight of cement was calculated. The samples were then
      stored for 24 hours at 100% humidity prior to tensile strength testing. RESULTS:
      Statistical analysis revealed significant differences in tensile strength across
      the groups. Further Tukey tests showed no significant difference in tensile
      strength between the practice abutment technique and the conventional technique
      for both definitive and provisional cements. There was a significant reduction in
      residual cement weight, irrespective of the type of cement, when the practice
      abutment was used prior to cementation. CONCLUSIONS: Cementation of implant
      restorations on a machined abutment using the practice abutment technique and
      definitive cement may provide similar uniaxial retention force and significantly
      reduced residual cement weight compared to the conventional technique of cement
      removal.

PMID- 21197492
TI  - The effect of splint material rigidity in implant impression techniques.
AB  - PURPOSE: This in vitro study compared the dimensional accuracy of two impression
      techniques: Duralay splinted impression copings (D) and metal splinted impression
      copings (M) for implant-supported prostheses. MATERIALS AND METHODS: A master
      cast with four parallel implant abutment analogs and a passive framework were
      fabricated. Vinyl polysiloxane impression material was used for all impressions
      with a metal stock tray. Two groups (D and M) were tested (n = 5). The
      measurement method employed was just one titanium screw tightened to the
      framework. Each group's measurements were analyzed using software that received
      the images of a video camera coupled to a stereomicroscope at 3100 magnification.
      The results were analyzed statistically (t test). RESULTS: The mean values of
      abutment/framework interface gaps were: master cast = 32 MUm (SD 2), group D =165
      MUm (SD 60), and group M = 69 MUm (SD 36). There was a statistically significant
      difference between the D and M groups (P ? .001). CONCLUSION: Under the
      limitations of this study, it could be suggested that a more accurate working
      cast can be fabricated using metal splinted impression copings.

PMID- 21197493
TI  - Osseoperception: active tactile sensibility of osseointegrated dental implants.
AB  - PURPOSE: The phenomenon of developing a certain tactile sensibility through
      osseointegrated dental implants is called osseoperception. Active tactile
      sensibility can be tested by having the subject bite on test bodies. The aim of
      the study was to describe the active tactile sensibility of single-tooth implants
      based on the 50% value and the slope of the sensibility curve at the 50% value.
      MATERIALS AND METHODS: Sixty-two subjects with single-tooth implants with natural
      opposing teeth were included in the study. In a computer-assisted and randomized
      way, copper foils of varying thickness (0 to 200 MUm) were placed
      inter?occlusally between the single-tooth implant and the natural opposing tooth,
      and the active tactile perception was studied according to the psychophysical
      method of constant stimuli and statistically evaluated by logistic regression.
      RESULTS: Tactile perception of the implants at the 50% value estimated by
      logistic regression was 20.2 +/- 10.9 MUm on average, and the slope was 29 +/-
      15. Regarding implant surface structure, significant differences were observed.
      The sandblasted and acid-etched surface was significantly more sensitive than the
      titanium plasma-sprayed surface, and the machined surface was similar to the
      titanium plasma-sprayed surface. CONCLUSIONS: Active tactile sensibility of
      implants with natural antagonistic teeth is very similar to that of teeth, but
      the slope of the tactile sensibility curve is flatter. Significant differences in
      tactile sensibility as a function of different implant surfaces may indicate that
      receptors near the implant form the basis of osseoperception.

PMID- 21197494
TI  - Posterior mandibular residual ridge resorption in patients with overdentures
      supported by two or four endosseous implants in a 10-year prospective comparative
      study.
AB  - PURPOSE: The aim of this study was to evaluate the effect of treatment with
      either two or four mandibular endosseous implants with an overdenture on
      mandibular posterior residual ridge resorption over a 10-year period. MATERIALS
      AND METHODS: Sixty edentulous patients with residual mandibular height between 12
      and 18 mm participated. Thirty patients were treated with an overdenture
      supported by two IMZ implants (group A) and 30 patients were treated with an
      overdenture with four IMZ implants (group B). Before treatment and 10 years after
      treatment, panoramic radiographs were taken and compared to ascertain possible
      bone loss. Proportional area measurements were used to determine changes in the
      mandibular posterior residual ridge bilaterally. RESULTS: There was a
      statistically significant difference in mandibular posterior residual ridge
      resorption between the two treatment protocols. The posterior bone area index was
      reduced by a mean of 10% for group A and 6% for group B over 10 years.
      CONCLUSIONS: There was a significant difference in mandibular posterior residual
      ridge resorption between patients treated with either two or four implants to
      stabilize an overdenture. No correlation was shown between mandibular posterior
      residual ridge resorption and peri-implant marginal bone loss. The confounding
      factors of marginal bone loss around the implants, age, gender, initial
      mandibular height, and the number of years the patient had been edentulous failed
      to show a significant effect on posterior ridge resorption.

PMID- 21197495
TI  - Immediate loading of the edentulous maxilla with a definitive restoration
      supported by an intraorally welded titanium bar and tilted implants.
AB  - PURPOSE: The aim of this prospective study was to evaluate the concept of
      intraoral welding as a suitable technique for the fabrication of a restoration
      for the edentulous atrophic maxilla on the day of placement of axial and tilted
      implants. MATERIALS AND METHODS: Thirty patients received three axial and four
      tilted implants in the edentulous maxilla. Immediately after implant placement,
      definitive abutments were connected to the implants and then a titanium bar was
      welded to them using an intraoral welding unit. This framework was used as a
      support for the definitive restoration, which was attached on the day of implant
      placement. Mean marginal bone loss and radiographically detectable alteration of
      the welded framework were assessed using periapical radiographs immediately after
      surgery and at 6, 12, 24, and 36 months after placement. RESULTS: Sixteen men and
      14 women with an average age of 58.1 years (SD 13.6) were consecutively treated
      with 210 immediately loaded implants. No fractures or radiographically detectable
      alterations of the welded frameworks were evident. A 100% prosthetic success rate
      was seen at 36 months. Three (1.4%) implants had serious biologic complications,
      resulting in success rates of 97.8% for axial implants and 99.2% for tilted
      implants. The accumulated mean marginal bone loss was 0.92 mm (SD 0.75; n = 90)
      for axial implants and 1.03 mm (SD 0.69; n = 120) for tilted implants. The
      average pocket probing depths were 1.87 mm (SD 0.98; n = 90) for the axial
      implants and 1.95 mm (SD 0.81; n = 120) for the tilted implants. CONCLUSIONS: It
      is possible on the day of implant placement surgery to successfully rehabilitate
      the edentulous atrophic maxilla with a fixed, definitive restoration supported by
      an intraorally welded titanium framework attached to axial and tilted implants.

PMID- 21197496
TI  - Buccal mucosal lesions caused by the interradicular miniscrew: a preliminary
      report.
AB  - PURPOSE: The purposes of this study were to examine the incidence of buccal
      mucosal lesions and identify factors affecting this complication caused by an
      interradicular miniscrew used as orthodontic anchorage. MATERIALS AND METHODS:
      Data from patients who used the Aarhus screw as orthodontic anchorage in the
      authors' practice from May 2003 to December 2008 were collected. The factors
      related to buccal injury during the use of miniscrews were evaluated using the
      Rank or Fisher exact test. Results were considered significant at P < .05.
      RESULTS: In all, 136 Aarhus screws in 54 patients were examined. The overall
      incidence of buccal lesions caused by interradicular miniscrews was 11.8%. The
      incidences of trauma were 10.4% in men and 12.5% in women, 9.5% in the maxilla
      and 12.8% in the mandible, 15.0% in patients with a high mandibular plane angle
      and 9.2% in patients with an average angle, and 28.1% with a miniscrew insertion
      angle between 10 and 30 degrees, 8.6% with an insertion angle between 30 and 60
      degrees, and 4.4% with an insertion angle between 60 and 80 degrees. There were
      statistically significant differences according to site of placement (P = .00)
      and occlusogingival position (P = .00). CONCLUSIONS: Interradicular miniscrews
      may be associated with damage to the buccal mucosa. For buccal mucosal lesions
      caused by interradicular miniscrews, site of placement and occlusogingival
      position are the major risk factors, and the angle of placement and the
      mandibular plane angle are secondary risk factors. The patient's sex and the arch
      in which the screw is placed (maxilla versus mandible) have little effect.

PMID- 21197497
TI  - Clinical evaluation of marginal bone level change of multiple adjacent implants
      restored with splinted and nonsplinted restorations: a 5-year prospective study.
AB  - PURPOSE: The success of single-tooth implant restorations has resulted in an
      increased use of nonsplinted implants to replace adjacent missing teeth; however,
      this may result in excessive force transmission to the implant and bone, causing
      bone loss. The purpose of this prospective study was to compare the marginal bone
      level change of adjacent splinted implants and of nonsplinted implants
      functionally loaded with cemented restorations up to 5 years in maxillae.
      MATERIAL AND METHODS: Between 2002 and 2004, all patients who received three
      consecutive adjacent implants in a private office and a university implant
      dentistry department were included in this study. All implants were placed in
      posterior maxillae. Maxillary left implants were restored with splinted cemented
      restorations, and maxillary right implants were restored with nonsplinted
      cemented restorations. Marginal bone resorption was measured with intraoral
      radiographs annually for 5 years. The data were analyzed statistically with the
      Mann-Whitney U test and the two-sample Kolmogorov-Smirnov test to identify
      differences between splinted and nonsplinted implant restorations. RESULTS: One
      hundred thirty-two implants were placed in 44 patients. Two subjects (6 implants
      in total) did not complete the study. Three implants failed at stage-two surgery.
      Of the remaining 123 implants, 63 were restored with splinted cemented
      restorations and 60 were restored with nonsplinted cemented restorations. The
      mean marginal bone level changes at the 5-year recall were -0.7 +/- 0.2 mm for
      splinted restorations and -0.8 +/- 0.2 mm) for nonsplinted restorations.
      CONCLUSIONS: Peri-implant marginal bone loss around nonsplinted implants in the
      present study was statistically equivalent to that observed in splinted implants.
      Multiple nonsplinted implants can be successfully included in many clinical
      situations in an effort to optimize esthetics and circumvent the problem of
      nonpassively fitting frameworks.

PMID- 21197498
TI  - Delayed function of dental implants: a 1- to 7-year follow-up study of 222
      implants.
AB  - PURPOSE: The aim of this study was to compare implant-supported restorations
      placed and loaded immediately or with a delay in a longitudinal case control
      study. MATERIALS AND METHODS: Seventy-six patients with 222 implants were
      enrolled in this study. One hundred eleven implants (45 patients) were submitted
      to immediate functional or nonfunctional loading. These were compared to 111
      implants (51 patients) that received delayed loading after submerged healing. The
      mean observation time was 40.3 months (3.36 years). Implant success was
      determined, and peri-implant soft tissue parameters and esthetic outcomes for
      anterior restorations were evaluated. The implants were divided into four groups
      according to their treatment protocol: immediate (I) or delayed (D) implant
      placement (P) or function (F), ie: group 1 = IF+IP, group 2 = IF+DP, group 3 =
      DF+IP, and group 4 = DF+DP. RESULTS: Five implants were lost during healing,
      giving an overall success rate of 97.7%. Implants with delayed function showed
      significantly better results (100.0%) than implants that were immediately loaded
      (95.5%). Four of the five lost implants had been placed immediately
      postextraction (success rate for delayed implant placement, 99.4%, versus 93.1%
      for immediate implant placement). Regarding the four treatment protocols, group 1
      showed a success rate of 91.3%; group 2 achieved 98.5%; and both delayed function
      groups showed 100% success. No statistically significant difference was seen
      between the four groups. Esthetically significant advantages were seen for the
      implants placed into immediate function. Probing depths and bleeding on probing
      were significantly lower in the group of implants placed into immediate function.
      CONCLUSIONS: Implants that are loaded immediately can achieve good outcomes.
      However, the risk of implant loss appears to be increased in cases where
      immediate function is combined with immediate implant placement.

PMID- 21197499
TI  - A prospective study of implants placed in augmented sinuses with minimal and
      moderate residual crestal bone: results after 1 to 5 years.
AB  - PURPOSE: The aims of this prospective study were to: (1) determine clinical and
      radiographic success and survival rates of implants placed in a staged procedure
      after sinus augmentation; and (2) compare the success and survival rate of
      implants in two patient groups with different ridge height prior to treatment
      (those with minimal residual crestal bone [? 3.5 mm] below the sinus and those
      with moderate residual crestal bone [> 3.5 mm]). MATERIALS AND METHODS: The study
      used anorganic bovine bone-derived mineral and autogenous bone for the sagittal
      sandwich bone augmentation technique, a collagen membrane to protect the sinus
      window, and a staged approach for implant placement; all implants featured an
      anodized surface. RESULTS: Two hundred forty-five implants were placed in 100
      sinus sites (79 patients), and 244 have survived to date. The cumulative success
      and survival rates of all implants overall at 5 years were 96.5% (SE 2.0%) and
      99.6% (SE 0.4%), respectively. The overall success and survival rates at 5 years
      for implants placed into minimal residual crestal bone were 94.1% (SE 3.4%) and
      99.4% (SE 0.6%), respectively. For implants placed into moderate crestal bone,
      overall success and survival rates were both 100.0% (SE 0.0%). CONCLUSIONS:
      Success of implants placed after sinus augmentation appears similar to implants
      placed in native bone when a classical submerged implant healing time of 6 months
      is used. The success and survival rates and crestal bone remodeling of implants
      placed in minimal residual crestal bone were comparable to those of implants
      placed in moderate residual crestal bone.

PMID- 21197500
TI  - Rehabilitation of the edentulous maxilla with the zygoma concept: a 7-year
      prospective study.
AB  - PURPOSE: The success of zygomatic implants following the two-stage, as well as
      the immediate loading, concept has been well documented. This graftless approach
      for the treatment of the completely edentulous resorbed maxilla allows for
      rehabilitation with an implant-supported fixed prosthesis. The purpose of this
      prospective study is to report on the 7-year follow-up of patients treated with
      zygomatic implants in conjunction with two to four anterior maxillary implants
      placed into immediate function and restored with a definitive fixed prosthesis.
      MATERIALS AND METHODS: This prospective study involved 36 patients treated with
      74 zygomatic implants and 98 anterior maxillary implants supporting fixed
      prostheses between 2003 and 2005. RESULTS: Two zygomatic implants in two patients
      were identified as mobile at stage-two surgery; replacement implants resulted in
      successful osseointegration. All anterior maxillary implants were determined as
      osseointegrated at stage two. Three patients experienced unilateral maxillary
      sinus infections that were refractory to oral antibiotics and were treated with
      functional endoscopic sinus surgery, which resolved the infections. All patients
      treated with the immediate loading concept were restored with definitive fixed
      profile prostheses as planned. CONCLUSION: The high survival rate, reduced
      morbidity, and high rate of patient acceptance for the zygomatic implant concept
      allowed the rehabilitation of the resorbed edentulous maxilla with fixed implant
      supported prosthesis, rendering this procedure a viable and a predictable
      treatment option.

PMID- 21197501
TI  - Comparison of radiographic and clinical outcomes following immediate
      provisionalization of single-tooth dental implants placed in healed alveolar
      ridges and extraction sockets.
AB  - PURPOSE: The primary goal of this study was to compare implant survival 12 months
      after immediate loading of single implants placed in healed ridges versus
      extraction sockets. Secondary outcomes were to compare marginal bone adaptation
      and soft tissue changes over time. MATERIALS AND METHODS: A prospective
      multicenter clinical investigation was initiated to assess clinical performance
      of immediately loaded implants in the maxilla. Implant survival was ascertained
      at the time of impression making (8 to 10 weeks) and after 1 year by clinical
      stability. Radiographic marginal bone levels, soft tissue levels, and plaque and
      bleeding scores were compared with baseline values (implant placement and
      provisionalization). RESULTS: One hundred thirty-nine patients received 157
      implants in the maxilla. Single implants with provisional crowns were placed in
      extraction sockets of 55 patients (58 implants) and in healed ridges of 60
      patients (65 implants). In addition, 19 patients (23 implants) required bone
      grafting prior to implant placement, and 11 implants in 10 patients among all
      groups were not immediately loaded because of insufficient initial stability
      after surgery. Three implants (5.2%) failed in extraction sites and one implant
      (1.5%) failed in a healed ridge. The mean change in marginal bone level 1 year
      after implant placement was 1.30 mm (SD 2.52) (gain) in extraction sockets and 
      0.40 mm (SD 1.43) (loss) in healed ridges. The mucosal zenith was stable or moved
      incisally following definitive crown placement in 83.7% of immediate implants and
      87.0% of implants placed in healed ridges. Plaque and inflammation scores were
      low and did not differ between groups. CONCLUSIONS: The responses of local bone
      and soft tissues at immediately loaded implants placed in extraction sockets or
      healed ridges were similar. Furthermore, these 1-year results suggest that
      clinical management of esthetically critical soft tissue may be predictably
      achieved in both indications.

PMID- 21197502
TI  - A new method to eliminate the risk of maxillary sinusitis with zygomatic
      implants.
AB  - PURPOSE: A new approach for zygomatic implant placement was proposed to eliminate
      the risk of maxillary sinusitis related to the procedure. MATERIALS AND METHODS:
      A prospective study of this new approach was conducted, and consecutive patients
      treated between June 2007 and December 2008 were included. An extended sinus lift
      with retained bone window was performed, such that zygomatic implants were placed
      completely outside the displaced maxillary sinuses. All patients were followed up
      radiologically at regular intervals using cone beam computed tomography to
      evaluate the status of the zygomatic implants and the condition of the maxillary
      sinuses. RESULTS: Sixteen patients (9 women and 7 men with a mean age of 60) were
      treated with 37 zygomatic implants. Within the period of investigation from 6
      months to 24 months, there were no failed zygomatic implants, and no instances of
      maxillary sinusitis were reported. CONCLUSIONS: The new approach that combined
      the zygomatic implant placement with the extended sinus lift procedure was
      predictable and fulfilled the purpose of lowering the risk of maxillary
      sinusitis.

PMID- 21197503
TI  - Complex prosthodontic treatment with dental implants for a patient with
      polymyalgia rheumatica: a clinical report.
AB  - Prosthodontic and implant treatment for a patient with polymyalgia rheumatica can
      be complicated not only by its symptoms, but also by the side effects of long
      term use of certain medications, particularly systemic glucocorticoids. This
      clinical report presents a polymyalgia rheumatica patient who required full-mouth
      rehabilitation with dental implants. The patient had a sensitive gag reflex and
      refused the use of any removable prostheses. She presented clinically with a
      skeletal Class II malocclusion with severe overbite and overjet. All her
      remaining dentition was determined to be unrestorable. Full-mouth extractions and
      immediate placement of implants followed by early implant loading were performed.
      The use of systemic glucocorticoids might have exacerbated her type 4 maxillary
      bone and compromised her healing capacity and consequently made implant surgery
      challenging. Her treatment with full-arch fixed implant-supported dentures to
      correct her severe overbite and overjet and manage misaligned dental implants is
      summarized here. The effects of polymyalgia rheumatica in prosthodontic and
      dental implant treatments are reviewed and discussed.

PMID- 21197504
TI  - The use of recombinant human bone morphogenetic protein-2 for the repair of
      extraction socket defects: a technical modification and case series report.
AB  - PURPOSE: The purpose of this case series was to evaluate the use of recombinant
      human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge
      (ACS) carrier for the repair of significant bone defects following tooth removal.
      The surgical technique was modified because primary closure was not obtained over
      the grafted sockets. MATERIALS AND METHODS: The present series included 10
      consecutively treated patients with failed endodontically treated maxillary
      central incisors. Computed tomographic scans were obtained preoperatively. The
      extraction sockets all had > 50% buccal bone loss. The sockets were grafted with
      rhBMP-2/ACS and a small amount of bone substitute. Dental implants were inserted
      after 4 to 6 months of healing. RESULTS: Healing of the grafted sockets was
      uneventful. Dental implants were placed in all grafted sites without the need for
      further bone augmentation. A comparison of preoperative and postgrafting computed
      tomographic scans found a slight loss in alveolar width at the crest of 1.07 mm.
      Connective tissue grafts were placed in five patients. All 10 implants integrated
      well and were restored with single crowns. CONCLUSIONS: The use of rhBMP-2/ACS
      was effective in repairing osseous defects prior to implant placement. The lack
      of primary closure over the graft did not appear to complicate healing or
      compromise bone growth. This modification simplifies the technique and may reduce
      postoperative morbidity caused by flap manipulation.

PMID- 21197505
TI  - Topical review. Dental pain and odontoblasts: facts and hypotheses.
AB  - Dental pain arises from exposed dentin following bacterial, chemical, or
      mechanical erosion of enamel and/or recession of gingiva. Thus, dentin tissue and
      more specifically patent dentinal tubules represent the first structure involved
      in dentin sensitivity. Interestingly, the architecture of dentin could allow for
      the transfer of information to the underlying dental pulp via odontoblasts
      (dentin-forming cells), via their apical extension bathed in the dentinal fluid
      running in the tubules, or via a dense network of trigeminal sensory axons
      intimately related to odontoblasts. Therefore, external stimuli causing dentinal
      fluid movements and odontoblasts and/or nerve complex responses may represent a
      unique mechanosensory system bringing a new role for odontoblasts as sensor
      cells. How cells sense signals and how the latter are transmitted to axons
      represent the main questions to be resolved. However, several lines of evidence
      have demonstrated that odontoblasts express mechano- and/or thermosensitive
      transient receptor potential ion channels (TRPV1, TRPV2, TRPV3, TRPV4, TRPM3,
      KCa, TREK-1) that are likely to sense heat and/or cold or movements of dentinal
      fluid within tubules. Added to this, voltage-gated sodium channels confer
      excitable properties of odontoblasts in vitro in response to injection of
      depolarizing currents. In vivo, sodium channels co-localize with nerve terminals
      at the apical pole of odontoblasts and correlate with the spatial distribution of
      stretch-activated KCa channels. This highlights the terminal web as the pivotal
      zone of the pulp/dentin complex for sensing external stimuli. Crosstalk between
      odontoblasts and axons may take place by the release of mediators in the gap
      space between odontoblasts and axons in view of evidence for nociception
      transducing receptors on trigeminal afferent fibers and expression of putative
      effectors by odontoblasts. Finally, how axons are guided to the target cells and
      which kind of signaling molecules are involved is extensively discussed in this
      review.

PMID- 21197506
TI  - Interstitial glutamate concentration is elevated in the masseter muscle of
      myofascial temporomandibular disorder patients.
AB  - AIM: To determine if myofascial temporomandibular disorder (TMD) pain patients
      have elevated interstitial concentrations of glutamate in the masseter muscle.
      METHODS: Thirteen patients (3 men, 10 women) diagnosed with myofascial TMD pain
      and 10 (2 men, 8 women) age-matched healthy controls participated in a single
      microdialysis session. Microdialysis was performed in the patients in the most
      painful point of the masseter muscle, while in the healthy subjects a
      standardized point in the muscle was chosen. Two microdialysis samples were
      collected over 40-minute epochs. A blood sample was also taken for analysis of
      plasma glutamate concentration. Numeric rating scale (NRS) scores of pain
      intensity and unpleasantness, McGill Pain Questionnaire data, pain drawing areas,
      pressure pain thresholds, pressure pain tolerances, maximum voluntary bite force,
      and maximum voluntary mouth opening were collected as secondary measurements.
      RESULTS: The median concentration of glutamate in the masseter muscle of the
      myofascial TMD pain patients (7.5 +/- 2.6 MUM) was significantly higher (P <
      .023, Mann-Whitney test) than the concentration in healthy controls (0.5 +/- 0.4
      MUM). There were, however, no significant correlations between glutamate
      concentrations in the masseter muscle and NRS pain scores. Plasma concentrations
      of glutamate were similar in patients and healthy controls. CONCLUSIONS: The
      present study demonstrates a marked increase in interstitial glutamate
      concentration in the masseter muscle of myofascial TMD pain patients. These novel
      findings suggest that peripheral glutamate could be involved in the
      pathophysiology of myofascial TMD pain.

PMID- 21197507
TI  - Prevalence of temporomandibular disorders: samples taken from attendees of
      medical health-care centers in the Islamic Republic of Iran.
AB  - AIMS: To determine the prevalence of facial pain and temporomandibular disorders
      (TMD) in people located in urban and rural areas in a newly industrialized
      country (Iran). METHODS: Two-hundred twenty-three subjects between 18 and 65
      years of age (mean: 32.07; SD: 10.83) were randomly selected from an urban area
      and a rural area. One-hundred nineteen subjects from Mashhad (major city) and 104
      subjects from Zoshk (village) were voluntarily recruited from medical health-care
      centers. Subjects who consulted the health-care center for dental, ear, nose, or
      throat issues were excluded. The monitoring of public health attendance of all
      citizens at designated health-care centers is compulsory by local law. All
      subjects were examined in accordance with the Research Diagnostic Criteria for
      TMD (RDC/TMD). Facial pain was assessed by using a questionnaire; the prevalence
      of myofascial pain, disc displacement, and degenerative disorders was determined
      by clinical examination. Nonparametric tests were used to assess group
      differences (ie, between village and city). RESULTS: Subjects in urban areas
      suffered less from facial pain (20.2% versus 46.2%; P < .01 [Mann-Whitney U
      test]) than subjects in rural areas. The frequency of TMD, disc displacement, and
      degenerative disorders was greater in the rural area. CONCLUSION: The symptoms
      under investigation were significantly more widespread in rural than in urban
      areas. With regard to TMD per se, the place of residence appears to be
      unimportant. However, the rural population was significantly affected by facial
      pain.

PMID- 21197508
TI  - Temporomandibular disorder patients' illness beliefs and self-efficacy related to
      bruxism.
AB  - AIMS: To examine temporomandibular disorder (TMD) patients' illness beliefs and
      self-efficacy in relation to bruxism, and to examine whether these beliefs are
      related to the severity of patients' self-perceived bruxing behavior. METHODS: A
      total of 504 TMD patients (75% women; mean age +/- SD: 40.7 +/- 14.6 years),
      referred to the TMD Clinic of the Academic Centre for Dentistry Amsterdam,
      completed a battery of questionnaires, of which one inquired about the frequency
      of oral parafunctional behaviors, including bruxism (clenching and grinding).
      Patients' illness beliefs were assessed with a question about the perceived
      causal relationship between bruxism and TMD pain; patients' self-efficacy was
      assessed with questions about the general possibility of reducing oral
      parafunctional behaviors and patients' own appraisal of their capability to
      accomplish this. RESULTS: Sleep bruxism or awake bruxism was attributed by 66.7%
      and 53.8% of the patients, respectively, as a cause of TMD pain; 89.9% believed
      that oral parafunctions could be reduced, and 92.5% believed themselves capable
      of doing so. The higher a patient's bruxism frequency, the more bruxism was
      believed to be the cause of TMD pain (Spearman's rho 0.77 and 0.71, P < .001) and
      the more pessimistic the self-efficacy beliefs were about the reducibility of
      oral parafunctions (Kruskal-Wallis ?2 = 19.91, df = 2, P < .001; and Kruskal
      Wallis ?2 = 7.15, df = 2, P = .028). CONCLUSION: Most TMD patients believe in the
      harmfulness of bruxism and the possibility of reducing this behavior. Bruxism
      frequency is associated with illness beliefs and self-efficacy.

PMID- 21197509
TI  - Two-year natural course of anterior disc displacement with reduction.
AB  - AIMS: To test if the disappearance of clicking associated with anterior disc
      displacement with reduction (ADDR) is related to a gradual loss of reducing
      capacity of the disc in the temporomandibular joint. MATERIALS: Twenty-five ADDR
      subjects without and 30 ADDR subjects with intermittent locking participated in
      this 2-year follow-up study. Clinical examinations and mandibular movement
      recordings were performed at baseline and after 1 and 2 years. If mandibular
      movement recordings no longer showed signs of an ADDR, magnetic resonance imaging
      (MRI) of the disc was carried out. RESULTS: Mandibular movement recordings showed
      the moment of disc reduction (MDR) to be stable over the observation period in
      the subjects without intermittent locking (P = .95). In the subjects with
      intermittent locking, MDR had shifted to a later mouth opening (P = .000). In
      seven of these subjects, clicking had totally disappeared, usually without
      symptoms of permanent locking. On the MRI scans of these subjects, the disc
      displacement was still present, but with no, or only a partial, reduction.
      CONCLUSION: Intermittent locking may be indicative of the development of a disc
      displacement without reduction. This loss is only rarely accompanied by symptoms
      of permanent locking.

PMID- 21197510
TI  - Changes in human primary motor cortex activity during acute cutaneous and muscle
      orofacial pain.
AB  - AIMS: To use functional magnetic resonance imaging (fMRI) to determine whether
      orofacial cutaneous or muscle pain is associated with changes in primary motor
      cortex (M1) activity that outlast the duration of perceived pain, and whether
      these M1 changes are different during cutaneous pain compared with muscle pain.
      METHODS: fMRI was used in healthy subjects experiencing orofacial muscle (n = 17)
      or cutaneous (n = 15) pain induced by bolus injections of hypertonic saline
      (4.5%) into the belly of the masseter muscle (0.5 ml) or subcutaneously (0.2 ml)
      into the overlying skin, respectively. To determine the effects of the injection
      volume, isotonic saline (n = 4) was injected into the masseter muscle. RESULTS:
      Similar pain scores were observed following subcutaneous (mean [+/- SEM]; 4.73 +/
      0.51) or intramuscular injections (4.35 +/- 0.56). Orofacial muscle but not
      cutaneous pain was associated with a transient increase in signal intensity in
      the contralateral M1. Cutaneous and muscle orofacial pains were associated with
      similar signal intensity decreases within the contralateral M1 that continued to
      decrease for the entire scanning period. Isotonic saline did not evoke pain or
      changes in M1 signal intensity. CONCLUSION: The transient contralateral M1 signal
      intensity increase during orofacial muscle pain may underlie escape-like motor
      patterns. However, once the initial threat has subsided, longer-term reductions
      in M1 activity and/or excitability may occur to aid in minimizing movement of the
      affected part, an effect consistent with the general proposals of the Pain
      Adaptation Model.

PMID- 21197511
TI  - Postcraniotomy temporalis muscle atrophy: a clinical, magnetic resonance imaging
      volumetry and electromyographic investigation.
AB  - AIMS: To evaluate both cosmetic and functional effects of temporalis muscle
      atrophy, by means of clinical examination, magnetic resonance imaging (MRI), and
      electromyographic (EMG) activity in patients who underwent craniotomy in order to
      treat refractory mesial temporal lobe epilepsy (MTLE). METHODS: A total of 18
      controls and 18 patients who underwent surgery for MTLE were investigated. The
      temporalis muscle volume of the patients was assessed by a 3D reconstruction. The
      image analysis software (ITK-SNAP) was used for the 3D reconstruction. In
      addition, the amplitude of the EMG signal during a maximum voluntary clench was
      recorded from both temporalis muscles by surface electrodes. The presence of
      temporomandibular disorder (TMD) signs was assessed by clinical examination that
      was performed only after surgery. Data were analyzed statistically by means of
      the Mann-Whitney U test, paired t-test, Pearson chi2 and linear regression.
      RESULTS: The volume of the temporalis muscle of the operated side was
      significantly reduced (P = .004). The EMG results confirmed the presence of
      muscle atrophy, the amplitude of the EMG signal being significantly decreased on
      the operated side (P < .05). Also the patients' maximum mouth opening after
      surgery was significantly reduced compared to that of the controls (P < .0001).
      Patients presented facial asymmetry, signs of TMD (pain, disc displacement, and
      joint sounds), and masticatory abnormalities. CONCLUSION: These preliminary
      results showed that, despite the good control of seizures, some patients may
      experience cosmetic and functional abnormalities of temporalis muscle secondary
      to atrophy and fibrosis.

PMID- 21197512
TI  - Effects of low-dose intramuscular ketorolac on experimental pain in the masseter
      muscle of healthy women.
AB  - AIMS: To investigate the effect of a low dose of intramuscular (im) ketorolac
      compared with lidocaine (LA) in a double-blinded, randomized, and controlled
      trial. METHODS: Twelve healthy women participated in three sessions and received
      two injections into their right masseter muscle per session. The first injections
      contained hypertonic saline (HS, 5% in 0.2 mL) to induce muscle pain. The second
      injections were given 30 minutes later and contained, together with HS, either
      ketorolac (3 mg in 0.2 mL), LA (2% lidocaine in 0.2 ml), or HS alone (control).
      HS-evoked pain intensity was scored on a 0 to 10 electronic visual analog scale
      (VAS) measuring peak, duration, and area under the curve (AUC). Pressure pain
      thresholds (PPT), pressure pain tolerance levels (PPTOL), and pain on palpation
      (POP) were determined bilaterally on the masseter muscle before and 5, 15, and 25
      minutes after the injections. Maximum jaw opening (MJO) was measured at baseline
      and every 10 minutes after. McGill Pain Questionnaire (MPQ) scores and the extent
      of the HS-evoked pain (pain drawings) were recorded at baseline, 2 minutes after
      the first and second injections, and every 10 minutes during the entire
      experimental session. RESULTS: There were no differences between the three
      sessions in HS-evoked pain measures from the first injection (P > .05). During
      the second injection, HS + LA demonstrated significantly lower VAS peak,
      duration, and AUC scores than control and HS + ketorolac (P < .001). In the HS +
      ketorolac session, the VAS AUC was significantly lower than in the control
      session (P < .005). The sessions had no main effect on PPT, PPTOL, POP, MJO, or
      pain drawings (P > .05). CONCLUSION: A low dose of im ketorolac has a significant
      and immediate analgesic effect on HS-evoked jaw muscle pain but significantly
      less than LA. A local anesthetic-like effect may be the underlying mechanism.

PMID- 21197513
TI  - Unnecessary extractions in patients with hemicrania continua: case reports and
      implication for dentistry.
AB  - Headache and facial pain are both very high in the general population. Headache
      has been identified as one of the associated conditions in patients with chronic
      orofacial pain. The interrelation between the two has not been explored in the
      literature. Patients with facial pain often initially seek the care of a dentist.
      Misdiagnosis and multiple failed treatments (including invasive procedures) are
      very common in this population. This case report describes four patients whose
      condition fulfilled the International Headache Society's criteria for hemicrania
      continua but whose teeth were extracted because their pain was suspected to be of
      odontogenic origin. Each patient's records and the literature were reviewed for
      possible reasons for the unnecessary extractions. The findings suggest that
      initial treatment with drugs specific for primary headache disorders should be
      instituted before subjecting patients to invasive procedures.

PMID- 21197514
TI  - Subacute trismus in a kidney transplant recipient.
AB  - This case report describes a male patient with trismus and generalized muscle
      weakness as the presenting symptom of disseminated malignancy. Trismus was caused
      by the presence of multiple small nests of undifferentiated tumor cells between
      muscle fibers of the masseter muscles as well as of other skeletal muscles. The
      diagnosis was suggested by increased uptake of 18-fluoro-deoxyglucose on positron
      emission tomography and subsequent ultrasound examination. The primary tumor was
      not found on autopsy. The patient was at increased risk for malignancy due to his
      renal transplantation 16 years before.

PMID- 21197515
TI  - Trends in the treatment and detection of skin cancer.

PMID- 21197516
TI  - Novel devices for diagnosis and treatment.

PMID- 21197517
TI  - Cosmeceutical and nutraceutical horizons.

PMID- 21197518
TI  - Medical management of skin disease: recent advances and future directions.

PMID- 21197519
TI  - Lasers and light therapy--a promising future awaits.

PMID- 21197520
TI  - Cosmetic laser treatments for skin of color: a focus on safety and efficacy.

PMID- 21197522
TI  - Rapid onset of response and patient-reported outcomes after onabotulinumtoxinA
      treatment of moderate-to-severe glabellar lines.
AB  - INTRODUCTION: no previously published botulinum toxin type A cosmetic trials
      included both physician and subject measures of onset. OBJECTIVE: determine
      physician- and subject-reported onset of onabotulinumtoxinA. METHODS: Two-center
      open-label, 14-day study in toxin-naive female patients with moderate-to-severe
      glabellar lines (GL) treated with 20-U onabotulinumtoxinA. Onset endpoint was
      categorical (physician assessed: days 2, 3, 4, 7 and 14; subject: 14-day diary).
      Subjects rated improvements in GL severity and completed the Facial Line Outcomes
      (FLO) and Self-Perception of Age (SPA) questionnaires. RESULTS: nearly half, 48
      percent (n=45) of subjects, reported onset by day 1. Subject- and physician
      reported onset rates, respectively, were 77 percent and 87 percent (day 2), 93
      percent and 91 percent (day 3), 98 percent and 100 percent (day 4), and 100
      percent thereafter. At all time points, FLO and SPA improved (P=0.008 and P=0.01,
      respectively). No serious adverse events occurred. CONCLUSION: onabotulinumtoxinA
      provides rapid onset (one to two days) based on physician and subject assessment.

PMID- 21197523
TI  - A 52-week study of safety and efficacy of calcium hydroxylapatite for
      rejuvenation of the aging hand.
AB  - OBJECTIVES: the investigator sought to determine whether calcium hydroxylapatite
      (CaHA) could be used as dermal filler for replacement of volume loss in aging
      hands. METHODS: the principal investigator injected 1.3 mL of CaHA into the
      dorsal side of both hands (BH) of 10 female patients (57-68 years of age), for
      full correction. Investigator, independent evaluator and subjects assessed
      results at four time points. RESULTS: safety. Brief and minor adverse events were
      reported. Efficacy. Wrinkle severity, improvement and patient satisfaction were
      assessed. Wrinkle Severity. Less severity was noted at 12 months than at
      baseline. Improvement. At nine months 80 percent of BH were rated as improved or
      better (IOB) and at 12 months 40 percent of right and 30 percent of left hands as
      IOB, approximating findings of the independent evaluator but at some variance
      from the subjects. Patient Satisfaction. At 12 months, 60 percent of subjects
      rated their results as "satisfactory" or better. CONCLUSION: in this study, CaHA
      performed well, with a favorable safety and durability profile. This application
      expands treatment options in patients seeking rejuvenation of the aging hand and
      face.

PMID- 21197524
TI  - Safety and efficacy comparison of blue versus red light sources for photodynamic
      therapy using methyl aminolevulinate in photodamaged skin.
AB  - BACKGROUND AND OBJECTIVE: methyl aminolevulinate (MAL) is a recently FDA-approved
      molecule for photodynamic therapy (PDT) in the treatment of nonhyperkeratotic
      actinic keratoses (AK). In the U.S., aminolevulinic acid (ALA) has been used in
      an off-label manner with photodynamic therapy for the treatment of chronic
      photodamage. The published use of MAL-PDT for photorejuvenation is more limited.
      MAL-PDT is usually conducted with a red light source, ALA-PDT with a blue light
      source. The purpose of this study is to compare the use of red versus blue light
      sources in the treatment of photodamage using MAL-PDT, measuring safety and
      efficacy outcomes following treatment. STUDY DESIGN/MATERIAL AND METHODS:
      eighteen adult patients with moderate-to-severe photodamage of the head or upper
      trunk were enrolled in a prospective, single center trial of MAL-PDT for
      photorejuvenation. Intrapatient randomization determined split-area treatment
      with a blue or red light source. The majority of patients were also treated with
      pulsed dye laser (PDL) and/or intense pulsed light (IPL) for photoactivation.
      Digitial photography documented the treatment area at each visit (days 0, 2, 7
      and 30). Patient and physician scoring of photodamage occurred at baseline and
      final visits. Side effects following MAL-PDT were evaluated. RESULTS: no
      statistically significant differences in signs of photodamage following MAL-PDT
      were observed between blue versus red light treated sides. The greatest
      improvement in photodamage measures following 1 MAL-PDT were pigmentation, AK and
      erythema. Side effects were mild in nature and did not differ between treatment
      sides, and all but mild erythema resolved by day 7. CONCLUSION: blue and red
      light have similar efficacy as the light source for MAL-PDT when combined with
      other light sources. Side effects following MAL-PDT with red versus blue light
      were similar and mild in severity. MAL-PDT is an effective treatment modality for
      chronic photodamage, in particular AK and pigmentation.

PMID- 21197525
TI  - Comparison of high-fluence, single-pass diode laser to low-fluence, multiple-pass
      diode laser for laser hair reduction with 18 months of follow up.
AB  - Laser hair removal is the most popular laser procedure in the United States
      (U.S.), yet there has not been a prospective study demonstrating long-term
      efficacy of diode laser hair removal beyond six months. A prospective, single
      center, bilaterally paired, blinded, randomized comparison split leg study was
      carried out with 22 patients comparing high-fluence, single-pass diode laser to
      low-fluence, multiple-pass diode laser. Hair counts were done six and 18 months
      following five treatment sessions and were found to be comparable t90-94 percent
      hair reduction. Hair counts at six months following the fifth treatment were
      comparable to hair counts at 18 months, indicating that sixth-month hair counts
      can be considered indicative of long-term results. The low-fluence, multiple-pass
      in-motion technique was associated with significantly less pain compared to the
      high-fluence, single-pass technique. Multiple passes of a diode laser at low
      fluences but with high average power results in permanent hair removal with less
      discomfort and fewer adverse effects, especially in darker skin.

PMID- 21197526
TI  - Use of gelatin sponges in Mohs micrographic surgery defects and staged melanoma
      excisions: a novel approach to secondary wound healing.
AB  - BACKGROUND/AIMS: surgical closure or reconstruction is commonly used to treat
      wounds generated by Mohs micrographic surgeries (MMS) and staged melanoma
      excisions, which may result in contractures and scarring. The authors' objective
      was to determine the value of using gelatin sponges to promote secondary
      intention healing for surgical defects after MMS and staged melanoma excisions.
      METHODS: sixty-four surgeries from 54 predominantly elderly patients (median
      age=76 years) were treated with gelatin sponges to promote healing by secondary
      intention in this prospective investigation. Patients rated their satisfaction
      with outcomes on a scale of 1 (highly dissatisfied) to 5 (highly satisfied).
      RESULTS: in all patients, the wounds healed within four to 16 weeks (median=five
      weeks). Forty-five patients were highly satisfied with their results (mean
      score=4.9). CONCLUSION: healing by secondary intention using gelatin sponges was
      associated with improved hemostasis, excellent cosmesis and a high level of
      patient satisfaction.

PMID- 21197527
TI  - Addition of chitosan may improve the treatment efficacy of triple bandage and
      compression in the treatment of venous leg ulcers.
AB  - INTRODUCTION: venous leg ulcers are an important problem in public health due to
      their high prevalence and treatment cost. The gold standard therapy is the
      compression bandage. Addition of different substances to the compression therapy
      in order to accelerate ulcer healing has been attempted but none of them has
      yielded optimal results. OBJECTIVE: to describe the treatment efficacy of venous
      leg ulcers treated with triple compression bandage and chitosan gel. METHODS: a
      longitudinal and descriptive study was conducted in a sample of 16 patients with
      26 venous leg ulcers that were treated with triple compression bandage plus a
      chitosan gel every seven days during nine weeks. Ulcer surface was measured
      during each treatment step. RESULTS: at the end of the treatment period, 89
      percent reduction of the ulcer area was found when compared to the initial area
      at the beginning of the study. This value represents a reduction rate of 1.8
      cm2/week. DISCUSSION: the results obtained in ulcer healing were higher than
      those previously reported when the compression bandage treatment of venous leg
      ulcers was performed alone. The observed difference might be due to the effect of
      the chitosan gel.

PMID- 21197528
TI  - Diffuse large B-cell lymphoma associated with the use of biologic and other
      investigational agents: the importance of long-term post-marketing safety
      surveillance.
AB  - This case report describes a patient who developed diffuse large B-cell lymphoma
      (DLBCL) after receiving courses of two investigational biologic agents and
      cyclosporine followed by more than four years of subcutaneous efalizumab for the
      treatment of extensive chronic plaque psoriasis. Three years later, the patient
      remains free of lymphoma and his psoriasis is well controlled with thrice-weekly
      narrow-band ultraviolet phototherapy. This case emphasizes the importance of
      continued long-term post-marketing safety surveillance and the early reporting of
      all possible serious side effects, including cancers, related to the use of any
      newly available product. In particular, surveillance should focus on the
      immunomodulating biologic agents in order to identify possible dangerous
      sequelae.

PMID- 21197529
TI  - A case of post-herpetic itch resolved with gabapentin.
AB  - Herpes zoster is a skin disease encountered commonly in dermatologic practice.
      While post-herpetic neuralgia (PHN) is a familiar side effect of this condition,
      it is not the only neuropathic symptom that can result. Post-herpetic itch (PHI)
      is less well known, but should be considered when evaluating a patient after an
      occurrence of zoster. Gabapentin has been successfully used to treat cutaneous
      pain and pruritus in a variety of conditions. The authors describe a case of PHI
      successfully treated with a course of gabapentin and propose that this agent be
      considered for use in patients who present with PHI.

PMID- 21197530
TI  - Attempted suicide among immigrants in European countries: an international
      perspective.
AB  - PURPOSE: This study compares the frequencies of attempted suicide among
      immigrants and their hosts, between different immigrant groups, and between
      immigrants and their countries of origin. METHODS: The material, 27,048 persons,
      including 4,160 immigrants, was obtained from the WHO/EURO Multicentre Study on
      Suicidal Behaviour, the largest available European database, and was collected in
      a standardised manner from 11 European centres in 1989-2003. Person-based suicide
      attempt rates (SARs) were calculated for each group. The larger immigrant groups
      were studied at each centre and compared across centres. Completed-suicide rates
      of their countries of origin were compared to the SARs of the immigrant groups
      using rank correlations. RESULTS: 27 of 56 immigrant groups studied showed
      significantly higher, and only four groups significantly lower SARs than their
      hosts. Immigrant groups tended to have similar rates across different centres.
      Moreover, positive correlation between the immigrant SAR and the country-of
      origin suicide rate was found. However, Chileans, Iranians, Moroccans, and Turks
      displayed high SARs as immigrants despite low suicide rates in the home
      countries. CONCLUSIONS: The similarity of most immigrant groups' SARs across
      centres, and the correlation with suicidality in the countries of origin suggest
      a strong continuity that can be interpreted in either cultural or genetic terms.
      However, the generally higher rates among immigrants compared to host populations
      and the similarity of the rates of foreign-born and those immigrants who retained
      the citizenship of their country of origin point to difficulties in the
      acculturation and integration process. The positive correlation found between
      attempted and completed suicide rates suggests that the two are related, a fact
      with strong implications for suicide prevention.

PMID- 21197531
TI  - Prevalence of mental disorders and trends from 1996 to 2009. Results from the
      Netherlands Mental Health Survey and Incidence Study-2.
AB  - OBJECTIVE: To present prevalences of lifetime and 12-month DSM-IV mood, anxiety,
      substance use and impulse-control disorders from the second Netherlands Mental
      Health Survey and Incidence Study (NEMESIS-2), and to compare the 12-month
      prevalence of mood, anxiety and substance use disorders with estimates from the
      first study (NEMESIS-1). METHOD: Between November 2007 and July 2009, a
      nationally representative face-to-face survey was conducted using the Composite
      International Diagnostic Interview 3.0 among 6,646 subjects aged 18-64. Trends in
      12-month prevalence of mental disorders were examined with these data and NEMESIS
      1 data from 1996 (n = 7,076). RESULTS: Lifetime prevalence estimates in NEMESIS-2
      were 20.2% for mood, 19.6% for anxiety, 19.1% for substance use disorder and 9.2%
      for impulse-control disorder. For 12-month disorders, these figures were 6.1,
      10.1, 5.6 and 2.1%, respectively. Between 1996 and 2007-2009, the 12-month
      prevalence of anxiety and substance use disorder did not change. The prevalence
      of mood disorder decreased slightly but lost significance after controlling for
      differences in sociodemographic variables between the two studies. CONCLUSION:
      This study shows that in the Netherlands mental disorders are prevalent. In about
      a decade, no clear change in mental health status was found.

PMID- 21197532
TI  - An analytical method for the simultaneous trace determination of acidic
      pharmaceuticals and phenolic endocrine disrupting chemicals in wastewater and
      sewage sludge by gas chromatography-mass spectrometry.
AB  - This article presents an analytical method based on solid-phase extraction (SPE)
      and gas chromatography coupled with mass spectrometry for the simultaneous
      determination of the most frequently used acidic pharmaceutical residues,
      ibuprofen, diclofenac, naproxen and ketoprofen (KFN), and phenolic endocrine
      disruptors, bisphenol (BPA), triclosan (TCS), nonylphenol, nonylphenol
      monoethoxylate and nonylphenol diethoxylate, in wastewater and sewage sludge
      samples. In the first phase of the study, each compound has been characterized
      individually and afterwards in mixture as a trimethylsilyl derivative in order to
      identify the characteristic ions (m/z ratio) constituting the mass spectrum and
      to choose the ions for quantification and confirmation. Subsequently,
      derivatization was evaluated by testing different variables such as the volume of
      the derivatization solvent bis(trimethylsilyl)trifluoroacetamide and the effect
      of each catalyst, pyridine and 1% trimethyl chlorosilane, in the derivatized
      solution. For the analysis of wastewater samples, two commercial SPE cartridges,
      C18 and Oasis HLB, were compared for their extraction efficiency of the target
      compounds. The key parameter of extraction procedure included the effect of pH
      (2.5, 5.3 and 7) of the loading solution. For solid samples, parameters such as
      the extracted biomass, the volume of the extraction organic solvent and the
      effect of matrix interferences in chromatographic analysis were evaluated. By
      using C18 cartridges as purification procedure and ultrasound sonication,
      satisfactory mean relative recoveries with BPA-d16 and meclofenamic acid as
      surrogates were obtained ranging from 91% to 117% for wastewater and 84% to 107%
      for sewage sludge samples. Nine-point calibration of the standard mixture was
      performed by linear regression analysis with a correlation coefficient >0.99 for
      all the tested compounds. Limits of detection for the developed methods were
      established between 0.3 (KFN) and 14.8 (BPA) ng L(-1), and 15.0 (TCS) and 32.9
      (BPA) ng g(-1) for wastewater and sewage sludge, respectively. Application to
      real samples of the wastewater treatment plant in Athens, the capital of Greece,
      demonstrated the presence of all tested compounds in most of the samples.

PMID- 21197533
TI  - Occult fractures of the scaphoid: the role of ultrasonography in the emergency
      department.
AB  - OBJECTIVE: To evaluate ultrasonography (US) performed by an emergency radiologist
      in patients with clinical suspicion of scaphoid fracture and normal radiographs.
      MATERIALS AND METHODS: Sixty-two consecutive adult patients admitted to our
      emergency department with clinical suspicion of scaphoid fracture and normal
      radiographs underwent US examination of the scaphoid prior to wrist computed
      tomography (CT), within 3 days following wrist trauma. US examination was
      performed by a board-certified emergency radiologist, non-specialized in
      musculoskeletal imaging, using the linear probe (5-13 MHz) of the standard
      sonographic equipment of the emergency department. The radiologist evaluate for
      the presence of a cortical interruption of the scaphoid along with a radio-carpal
      or scapho-trapezium-trapezoid effusion. A CT of the wrist (reference standard)
      was performed in every patient, immediately after ultrasonography. Fractures were
      classified into two groups according to their potential for complication: group 1
      (high potential, proximal or waist), group 2 (low-potential, distal or tubercle).
      RESULTS: A scaphoid fracture was demonstrated by CT in 13 (21%) patients: eight
      (62%) of them belonged to group 1 (three in the proximal pole, five in the
      waist), five (38%) to group 2 (three in the distal part, two in the tubercle). US
      was 92% sensitive (12/13) in demonstrating a scaphoid fracture. It was 100%
      sensitive (8/8) in demonstrating a fracture with a high potential of complication
      (group 1). CONCLUSIONS: Our data show that, in emergency settings, US can be used
      for the triage to CT in patients with clinical suspicion of scaphoid fracture and
      normal radiographs.

PMID- 21197534
TI  - Feasibility of diffusion tensor imaging (DTI) with fibre tractography of the
      normal female pelvic floor.
AB  - OBJECTIVES: To prospectively determine the feasibility of diffusion tensor
      imaging (DTI) with fibre tractography as a tool for the three-dimensional (3D)
      visualisation of normal pelvic floor anatomy. METHODS: Five young female
      nulliparous subjects (mean age 28 +/- 3 years) underwent DTI at 3.0T. Two
      dimensional diffusion-weighted axial spin-echo echo-planar (SP-EPI) pulse
      sequence of the pelvic floor was performed, with additional T2-TSE multiplanar
      sequences for anatomical reference. Fibre tractography for visualisation of
      predefined pelvic floor and pelvic wall muscles was performed offline by two
      observers, applying a consensus method. Three eigenvalues (lambda1, lambda2,
      lambda3), fractional anisotropy (FA) and mean diffusivity (MD) were calculated
      from the fibre trajectories. RESULTS: In all subjects fibre tractography resulted
      in a satisfactory anatomical representation of the pubovisceral muscle, perineal
      body, anal - and urethral sphincter complex and internal obturator muscle. Mean
      FA values ranged from 0.23 +/- 0.02 to 0.30 +/- 0.04, MD values from 1.30 +/-
      0.08 to 1.73 +/- 0.12 * 10(-)3 mm2/s. Muscular structures in the superficial
      layer of the pelvic floor could not be satisfactorily identified. CONCLUSIONS:
      This study demonstrates the feasibility of visualising the complex three
      dimensional pelvic floor architecture using 3T-DTI with fibre tractography. DTI
      of the deep female pelvic floor may provide new insights into pelvic floor
      disorders.

PMID- 21197535
TI  - Interactive effects of development and hypoxia on catecholamine synthesis and
      cardiac function in zebrafish (Danio rerio).
AB  - The rate-limiting enzyme in the biosynthetic pathway of catecholamines is
      tyrosine hydroxylase (TH), the activity of which is dependent on molecular
      oxygen. Zebrafish (Danio rerio) possess two non-allelic TH coding genes, TH1 and
      TH2. A principal goal of the present study was to determine if the expression of
      these genes is sensitive to environmental hypoxia. Additionally, we sought to
      determine if catecholamine content of larvae was changed by environmental
      hypoxia, and whether the hearts of hypoxic larvae were equally responsive to
      exogenous catecholamine (norepinephrine) exposure. After 2 days of exposure to
      hypoxia [5-7 days post-fertilization (dpf); PO(2) = 30 Torr] TH2 mRNA expression
      was significantly lower and dopamine beta hydroxylase (DbetaH) mRNA was
      significantly higher in whole larvae. Whole body catecholamine levels were
      unchanged until after 4 days of hypoxic exposure (5-9 dpf), at which time there
      was a significant increase in epinephrine and norepinephrine contents.
      Norepinephrine content was significantly elevated in the hearts of adult fish
      after 2 and 4 days of hypoxic exposure, and TH1 mRNA expression was increased in
      the kidney of both groups. After 2 or 4 days of exposure to hypoxia, larvae
      displayed significantly lower heart rates than normoxic fish. However,
      application of exogenous norepinephrine caused similar increases in heart rate in
      both groups. Overall, it is concluded that the mRNA expression of TH1 and TH2 is
      differentially affected by hypoxia exposure in larvae and adults. Also,
      catecholamine biosynthesis appears to be activated by 2 dpf and although whole
      body catecholamine levels increase during hypoxia (possibly promoting
      downregulation of cardiac beta-adrenergic receptors), there is no accompanying
      decrease in the response of the heart to adrenergic stimulation.

PMID- 21197536
TI  - Effect of levosimendan and predictors of recovery in patients with peripartum
      cardiomyopathy, a randomized clinical trial.
AB  - BACKGROUND: Levosimendan is a promising new inodilator agent but its
      effectiveness in peripartum cardiomyopathy (PPCM) has not been tested in a
      clinical trial. The authors sought to evaluate the effect of levosimendan therapy
      and to determine the predictors of clinical outcome in patients with PPCM.
      METHODS AND RESULTS: The authors prospectively randomized 24 consecutive women
      with PPCM. Twelve patients (control group) were randomized to conventional heart
      failure therapy and 12 patients (levosimendan group) were randomized to
      levosimendan in addition to the conventional therapy. Mean follow-up period was
      20.9 +/- 9 months (ranged 12-38 months). The two groups did not differ in
      baseline demographic and echocardiographic characteristics. Eleven patients
      (45.8%) recovered completely (6 in control group and 5 in levosimendan group, p >
      0.05), 6 died (25%) (3 in control group and 3 in levosimendan group), and 7
      (29.1%) were left with persistent left ventricular dysfunction (PLVD) (3 in
      control group and 4 in levosimendan group, p > 0.05). There were significant
      differences in baseline characteristics between deceased patients and survivors
      including left ventricular end-diastolic diameter (7.1 +/- 0.6 vs. 6.4 +/- 0.5
      cm, p = 0.031), left ventricular end-systolic diameter (LVESD) (6.4 +/- 0.8 vs.
      5.5 +/- 0.6 cm, p = 0.027), left ventricular ejection fraction (LVEF) (19.7 vs.
      27.4%, p = 0.025), and left atrial diameter (4.9 +/- 0.3 vs. 4.3 +/- 0.4 cm, p =
      0.011). CONCLUSIONS: Addition of levosimendan to conventional therapy did not
      improve outcome in patients with PPCM. In patients with PLVD or patients who
      died, LVEF, LVESD and left atrial diameter were worse than those with complete
      resolution.

PMID- 21197537
TI  - Anti-platelet effects of olive oil extract: in vitro functional and proteomic
      studies.
AB  - PURPOSE: Platelets play a key role in haemostasis and wound healing, contributing
      to formation of vascular plugs. They are also involved in formation of
      atherosclerosic plaques. Some traditional diets, like the Mediterranean diet, are
      associated with a lower risk of cardiovascular disease. Components in these diets
      may have anti-platelet functions contributing to their health benefits. METHODS:
      We studied the effects of alperujo extract, an olive oil production waste product
      containing the majority of polyphenols found in olive fruits, through measurement
      of effects on platelet aggregation and activation in isolated human platelets,
      and through identification of changes in the platelet proteome. RESULTS: Alperujo
      extract (40 mg/L) significantly decreased in vitro ADP- (p = 0.002) and TRAP- (p
      = 0.02) induced platelet activation as measured by the flow cytometry using the
      antibody for p-selectin (CD62p), but it did not affect the conformation of the
      fibrinogen receptor as measured by flow cytometry using the antibodies for anti
      fibrinogen, CD42a and CD42b. Alperujo extract (100 mg/L) inhibited both collagen-
      and TRAP-induced platelet aggregation by 5% (p < 0.05), and a combination of
      hydroxytyrosol and 3,4-dihydroxyphenylglycol were, at least partly, responsible
      for this effect. Proteomic analysis identified nine proteins that were
      differentially regulated by the alperujo extract upon ADP-induced platelet
      aggregation. These proteins represent important mechanisms that may underlie the
      anti-platelet effects of this extract: regulation of platelet structure and
      aggregation, coagulation and apoptosis, and signalling by integrin
      alphaIIb/beta3. CONCLUSIONS: Alperujo extract may protect against platelet
      activation, platelet adhesion and possibly have anti-inflammatory properties.

PMID- 21197538
TI  - Impairment of cardiac insulin signaling in fructose-fed ovariectomized female
      Wistar rats.
AB  - BACKGROUND: Fructose consumption produces deleterious metabolic effects in animal
      models. The sites of fructose-induced insulin resistance are documented to be the
      liver, skeletal muscle, and adipose tissue, but effects of fructose-rich diet on
      cardiac insulin signaling and action were not investigated. PURPOSE AND METHODS:
      In order to study the potential fructose effects on development of cardiac
      insulin resistance, we analyzed biochemical parameters relevant for insulin
      action and phosphorylation of insulin signaling molecules, plasma membrane
      glucose transporter type 4 (GLUT4) content, and phosphorylation of endothelial
      nitric oxide synthase (eNOS), in ovariectomized female rats on fructose-enriched
      diet, in basal and insulin-stimulated conditions. RESULTS: Fructose-fed rats
      (FFR) had increased content of visceral adipose tissue, but not body weight. Food
      intake was decreased, while fluid and caloric intake were increased in FFR.
      Additionally, fructose diet increased plasma insulin, blood triglycerides level,
      and HOMA index. Stimulation of protein kinase B (Akt) signaling pathway by
      insulin was reduced in rats on fructose-enriched diet, but effect of fructose on
      extracellular signal-regulated kinase (Erk 1/2) phosphorylation was not observed.
      Furthermore, insulin-induced GLUT4 presence in plasma membranes of cardiac cells
      was decreased by fructose diet, as well as insulin stimulation of eNOS
      phosphorylation at Ser(1177). CONCLUSION: In summary, these results strongly
      support our hypothesis that fructose diet-induced changes of plasma lipid profile
      and insulin sensitivity are accompanied with decrease in cardiac insulin action
      in ovariectomized female rats.

PMID- 21197539
TI  - Disease- and treatment-related effects on the pituitary-gonadal functional axis:
      a study in men with epilepsy.
AB  - The consideration of the patient's gender has become an established practice in
      the choice of antiepileptic drugs (AEDs) for the treatment of epilepsy. This
      study was undertaken to confirm that temporal lobe epilepsy and the use of
      hepatic enzyme-inducing AEDs, have a negative effect on sex hormones in men. We
      calculated the testosterone (T)/luteinizing hormone (LH) ratio to reflect the
      effects of epilepsy or its treatment on the most important androgen and its
      pituitary control hormone. Of 324 men with focal epilepsy identified (untreated
      or on AED monotherapy), 201 were eligible for inclusion (mean age 37.5 years,
      mean duration of epilepsy 14.7 years). A total of 105 men served as healthy
      controls (mean age 33.9 years). Patients with temporal lobe epilepsy were more
      likely to show abnormal T/LH ratios than patients with extratemporal epilepsy (p
      < 0.01). Patients receiving AEDs with marked hepatic enzyme-inducing effects were
      more likely to have low T/LH ratios than patients taking nonenzyme-inducing AEDs
      or healthy controls (p < 0.01). Focus localization and AED choice affect male sex
      hormones. Findings raise some concerns about the effect of enzyme-inducing AEDs
      on sexual endocrine functions.

PMID- 21197540
TI  - Evolution of dose and response to botulinum toxin A in cervical dystonia: a
      multicenter study.
AB  - Botulinum neurotoxin (BoNT) is an effective treatment for cervical dystonia (CD).
      Long-term changes of several variables, including the dose of BoNT, in these
      patients is largely unknown. We reviewed the clinical charts of 275 patients with
      CD treated with BoNT type A (BoNT-A) for at least 5 years since 1989 at ten
      tertiary centers. The mean dose of BoNT-A per session during the first 5 years of
      treatment was calculated and the appearance of resistance was noted. The dose of
      BoNT-A for the whole group showed a significant trend to increase over time (year
      1: 180 +/- 65 U; year 5: 203 +/- 63 U; ANOVA: p < 0.0001). However, when we
      studied the evolution of the dose of BoNT-A for those patients (n = 49) first
      injected after 2000 (introduction of current BOTOX preparation in our country),
      there was no significant increase in dose (year 1: 181.8 +/- 75 U; year 5: 181.7
      +/- 75 U; ANOVA p: ns). A total of 19 patients became secondary nonresponders;
      all but one of these patients began BoNT-A treatment before 2000. In summary,
      there is a statistically significant increase of mean dose of BoNT-A per session
      over time, and this could be explained by the appearance of secondary
      nonresponders. On the other hand, those patients initially treated after 2000 did
      not show any statistically significant increase in dose for 5 years. This could
      be explained by better experience and techniques, fewer immunogenic problems with
      the current BoNT-A, and also less variability of the dose per vial.

PMID- 21197541
TI  - Glial fibrillary acidic protein: a potential biomarker for progression in
      multiple sclerosis.
AB  - The major intermediate cytoskeletal protein of astrocytes, glial fibrillary
      acidic protein (GFAP), and that of axons, neurofilament light protein (NFL), may
      both be released into the cerebrospinal fluid (CSF) during pathological processes
      in the central nervous system (CNS). We investigated GFAP and NFL levels in CSF
      as possible biomarkers for progression in multiple sclerosis (MS). Patients with
      relapsing-remitting MS (RRMS, n = 15) or secondary progressive MS (SPMS, n = 10)
      and healthy control subjects (n = 28) were examined twice with an interval of 8
      10 years apart. Neurological deficits were scored with the Expanded Disability
      Status Scale (EDSS). GFAP and NFL levels were determined in CSF by enzyme-linked
      immunosorbent assay (ELISA). GFAP levels and NFL levels correlated with age (r
      and r (s) = 0.50, p = 0.006). Adjusting for age, MS patients had increased GFAP
      levels compared with controls (p = 0.03) and GFAP levels correlated with
      neurological disability (EDSS, r = 0.51, p < 0.05) and disease progression
      [Multiple Sclerosis Severity Score (MSSS), r = 0.47, p < 0.05]. The mean annual
      increase of GFAP was 6.5 ng/L for controls, 8.1 ng/L for RRMS patients, and 18.9
      ng/L for SPMS patients. GFAP level at the first examination had predictive value
      for neurological disability 8-10 years later (EDSS, r = 0.45, p < 0.05) but not
      for EDSS increase between the examinations. NFL levels were not significantly
      increased in MS patients compared with controls and had no relationship to
      disability or progression and no prognostic value for disability development.
      GFAP, a marker for astrogliosis, is a potential biomarker for MS progression and
      may have a role in clinical trials for assessing the impact of therapies on MS
      progression.

PMID- 21197542
TI  - Effects of bicarbonate ingestion and high intensity exercise on lactate and H(+)
      ion distribution in different blood compartments.
AB  - Lactate (La) and H(+)-ions are unequally distributed in the blood between plasma
      and red blood cells (RBCs). To our knowledge there is no data concerning the
      effects of an oral ingestion of bicarbonate (HCO(3) (-)) on repeated high
      intensity sprint exercise and La and H(+) distribution between plasma and RBCs.
      Since an oral ingestion of HCO(3) (-) leads to a higher efflux of La from the
      working skeletal muscle to the plasma, as it was shown by previous studies, this
      would lead to a higher gradient of La between plasma and RBCs. Although a higher
      gradient leads to a higher uptake, it is even more difficult for the RBCs to take
      up La fast enough, due to the more stressed transport system. Since RBCs function
      to transport La from the working muscle and help to maintain a concentration
      difference between plasma and muscle, this potentially increases performance
      during repeated sprint exercise (e.g. 4 * 30 s). The major goal of the present
      investigation was to test this hypothesis. 11 male participants ingested either a
      solution of sodium bicarbonate (NaHCO(3)) or placebo (CaCO(3)). Thereafter all
      performed four maximal 30 s sprints with 5 min of passive rest. During the
      resting periods concentrations of HCO(3) (-), La and H(+) where measured in both
      blood compartments (plasma and RBCs). There were no significant differences in
      the La-ratios between plasma and RBCs between both interventions. These results
      indicate that the La/H(+) co-transport is not affected by an oral ingestion on
      NaHCO(3).

PMID- 21197543
TI  - Skin temperature as a thermal controller of exercise intensity.
AB  - This study examined the role of skin temperature on self-selected exercise
      intensity (i.e., power output). Eight well-trained, male cyclists completed two
      60 min self-paced cycling bouts during which they completed as much work as
      possible. Using a liquid-perfused suit, skin temperature (T (Sk)) was changed
      during the two trials such that T (Sk) either started hot and was cooled (H to C)
      or started cold and was heated (C to H) throughout exercise. Pre-exercise core
      temperatures (T (C)) and heart rates (HR) were similar between trials, while T
      (Sk), thermal comfort and thermal sensation were higher in H to C. The change in
      T (Sk) was similar in magnitude during the two trials. Work completed was
      greatest in C to H, which was attributed to a higher initial power output. T (C)
      was similar between trials. HR was similar until 35 min had elapsed, after which
      it became lower in H to C. The perception of effort increased similarly between
      the two trials, while thermal comfort and thermal sensation generally reflected
      the changes observed in T (Sk). These results indicate that upon exercise
      commencement T (Sk) and the accompanying thermal perceptions are important inputs
      in the initial selection of exercise intensity.

PMID- 21197544
TI  - Functional plant cell wall design revealed by the Raman imaging approach.
AB  - Using the Raman imaging approach, the optimization of the plant cell wall design
      was investigated on the micron level within different tissue types at different
      positions of a Phormium tenax leaf. Pectin and lignin distribution were
      visualized and the cellulose microfibril angle (MFA) of the cell walls was
      determined. A detailed analysis of the Raman spectra extracted from the selected
      regions, allowed a semi-quantitative comparison of the chemical composition of
      the investigated tissue types on the micron level. The cell corners of the
      parenchyma revealed almost pure pectin and the cell wall an amount of 38-49%
      thereof. Slight lignification was observed in the parenchyma and collenchyma in
      the top of the leaf and a high variability (7-44%) in the sclerenchyma. In the
      cell corners and in the cell wall of the sclerenchymatic fibres surrounding the
      vascular tissue, the highest lignification was observed, which can act as a
      barrier and protection of the vascular tissue. In the sclerenchyma high variable
      MFA (4 degrees -40 degrees ) was detected, which was related with lignin
      variability. In the primary cell walls a constant high MFA (57 degrees -58
      degrees ) was found together with pectin. The different plant cell wall designs
      on the tissue and microlevel involve changes in chemical composition as well as
      cellulose microfibril alignment and are discussed and related according to the
      development and function.

PMID- 21197545
TI  - A comparison of suberin monomers from the multiseriate exodermis of Iris
      germanica during maturation under differing growth conditions.
AB  - Iris germanica roots develop a multiseriate exodermis (MEX) in which all mature
      cells contain suberin lamellae. The location and lipophilic nature of the
      lamellae contribute to their function in restricting radial water and solute
      transport. The objective of the current work was to identify and quantify
      aliphatic suberin monomers, both soluble and insoluble, at specific stages of MEX
      development and under differing growth conditions, to better understand aliphatic
      suberin biosynthesis. Roots were grown submerged in hydroponic culture, wherein
      the maturation of up to three exodermal layers occurred over 21 days. In
      contrast, when roots were exposed to a humid air gap, MEX maturation was
      accelerated, occurring within 14 days. The soluble suberin fraction included
      fatty acids, alkanes, fatty alcohols, and ferulic acid, while the suberin
      poly(aliphatic) domain (SPAD) included fatty acids, alpha,omega-dioic acids,
      omega-OH fatty acids, and ferulic acid. In submerged roots, SPAD deposition
      increased with each layer, although the composition remained relatively constant,
      while the composition of soluble components shifted toward increasing alkanes in
      the innermost layers. Air gap exposure resulted in two significant shifts in
      suberin composition: nearly double the amount of SPAD monomers across all layers,
      and almost three times the alkane accumulation in the first layer. The localized
      and abundant deposition of C18:1 alpha,omega-dioic and omega-OH fatty acids,
      along with high accumulation of intercalated alkanes in the first mature
      exodermal layer of air gap-exposed roots indicate its importance for water
      retention under drought compared with underlying layers and with entire layers
      developing under water.

PMID- 21197546
TI  - Differences in susceptibility to Saprolegnia infections among embryonic stages of
      two anuran species.
AB  - Many amphibians are known to suffer embryonic die-offs as a consequence of
      Saprolegnia infections; however, little is known about the action mechanisms of
      Saprolegnia and the host-pathogen relationships. In this study, we have isolated
      and characterized the species of Saprolegnia responsible for infections of
      embryos of natterjack toad (Bufo calamita) and Western spadefoot toad (Pelobates
      cultripes) in mountainous areas of Central Spain. We also assessed the influence
      of the developmental stage within the embryonic period on the susceptibility to
      the Saprolegnia species identified. Only one strain of Saprolegnia was isolated
      from B. calamita and identified as S. diclina. For P. cultripes, both S. diclina
      and S. ferax were identified. Healthy embryos of both amphibian species suffered
      increased mortality rates when exposed to the Saprolegnia strains isolated from
      individuals of the same population. Embryonic developmental stage was crucial in
      determining the sensitivity of embryos to Saprolegnia infection. The mortalities
      of P. cultripes and B. calamita embryos exposed at Gosner stages 15 (rotation)
      and 19 (heart beating) were almost total 72 h after challenge with Saprolegnia,
      while those exposed at stage 12 (late gastrula) showed no significant effects at
      that time. This is the first study to demonstrate the role of embryonic
      development on the sensitivity of amphibians to Saprolegnia.

PMID- 21197547
TI  - Patterns and controls of seasonal variability of carbon stable isotopes of
      particulate organic matter in lakes.
AB  - Carbon stable isotopes (delta(13)C) of particulate organic matter (POM) have been
      used as indicators for energy flow, primary productivity and carbon dioxide
      concentration in individual lakes. Here, we provide a synthesis of literature
      data from 32 freshwater lakes around the world to assess the variability of
      delta(13)C(POM) along latitudinal, morphometric and biogeochemical gradients.
      Seasonal mean delta(13)C(POM), a temporally integrated measure of the
      delta(13)C(POM), displayed weak relationships with all trophic state indices
      [total phosphorus (TP), total nitrogen (TN), and chlorophyll a (Chl a)], but
      decreased significantly with the increase in latitude, presumably in response to
      the corresponding decrease in water temperature and increase in CO(2)
      concentration. The seasonal minimum delta(13)C(POM) also correlated negatively
      with latitude while seasonal maximum delta(13)C(POM) correlated positively with
      all trophic state indices, pH, and delta(13)C of dissolved inorganic carbon
      (DIC). Seasonal amplitude of delta(13)C(POM) (the difference between seasonal
      maximum and minimum values) correlated significantly with pH, TP and Chl a
      concentrations and displayed small variations in oligotrophic, mesotrophic and
      low latitude eutrophic lakes, which is attributed to low primary productivity and
      abundant non-living POM in the low trophic state lakes and relatively stable
      environmental conditions in the subtropics. Seasonal amplitude of delta(13)C(POM)
      was the greatest in high latitude eutrophic lakes. Greater seasonal changes in
      solar energy and light regime may be responsible for the large seasonal
      variability in high latitude productive lakes. This synthesis provides new
      insights on the factors controlling variations in stable carbon isotopes of POM
      among lakes on the global scale.

PMID- 21197548
TI  - Single-port laparoscopic total proctocolectomy with ileal pouch-anal anastomosis:
      initial operative experience.
AB  - BACKGROUND: Single-port laparoscopic surgery (SPLS) has been used in urologic,
      gynecologic, general, and colorectal surgery. We herein report our experience
      with the use of SPLS for total proctocolectomy with ileal pouch-anal anastomosis
      (RP/IPAA). METHODS: All patients who underwent a RP/IPAA using SPLS between June
      and September 2009 were identified from a prospectively maintained laparoscopic
      database. All procedures were performed with the use of a 5-mm Olympus EndoEyeTM
      and traditional laparoscopic instruments via a SILSTM port placed at the planned
      ileostomy site. RESULTS: There were five patients (3 male) included in the study.
      Median age was 43 years (range=13-47 years). Median body mass index was 20.66
      kg/m2 (range=14.63-25.97 kg/m2). Diagnoses included ulcerative colitis (n=4) and
      familial adenomatous polyposis (n=1). Median ASA score was 2 (range=1-3). Median
      operative time was 153 min (range=132-278 min). Median estimated blood loss was
      100 ml (range=50-200 ml). There were no conversions to either a conventional
      laparoscopic or an open procedure. Median time to return of bowel function was 2
      days. Median length of stay was 4 days (range=3-6 days). Postoperative
      complications included two patients with partial small-bowel obstructions. Both
      resolved with conservative management. All patients had their ileostomies closed.
      CONCLUSION: RP/IPAA using SPLS is a safe technique. Additional studies are needed
      to compare SPLS to conventional laparoscopy and open surgery with respect to
      operative times, convalescence, and outcomes.

PMID- 21197549
TI  - Outdoor thermal comfort study in a sub-tropical climate: a longitudinal study
      based in Hong Kong.
AB  - This paper presents the findings of an outdoor thermal comfort study conducted in
      Hong Kong using longitudinal experiments--an alternative approach to conventional
      transverse surveys. In a longitudinal experiment, the thermal sensations of a
      relatively small number of subjects over different environmental conditions are
      followed and evaluated. This allows an exploration of the effects of changing
      climatic conditions on thermal sensation, and thus can provide information that
      is not possible to acquire through the conventional transverse survey. The paper
      addresses the effects of changing wind and solar radiation conditions on thermal
      sensation. It examines the use of predicted mean vote (PMV) in the outdoor
      context and illustrates the use of an alternative thermal index--physiological
      equivalent temperature (PET). The paper supports the conventional assumption that
      thermal neutrality corresponds to thermal comfort. Finally, predictive formulas
      for estimating outdoor thermal sensation are presented as functions of air
      temperature, wind speed, solar radiation intensity and absolute humidity.
      According to the formulas, for a person in light clothing sitting under shade on
      a typical summer day in Hong Kong where the air temperature is about 28 degrees C
      and relative humidity about 80%, a wind speed of about 1.6 m/s is needed to
      achieve neutral thermal sensation.

PMID- 21197550
TI  - Risk of renal failure in cancer patients with bone metastasis treated with
      renally adjusted zoledronic acid.
AB  - PURPOSE: The purpose of this study was to evaluate the incidence of acute renal
      failure (ARF) in patients with mild to moderate renal dysfunction, receiving
      renally adjusted zoledronic acid (ZA) and compare it to patients with normal
      baseline renal function, receiving standard-dose ZA. METHODS: This was a
      retrospective study of patients receiving ZA for the treatment of bone metastasis
      due to cancer. Patients were divided into two groups: (1) normal group with
      baseline creatinine clearance (CrCl) of greater than 60 mL/min and standard ZA
      dose; (2) impaired group with baseline CrCl of 30-60 mL/min and renally adjusted
      ZA dose. Primary endpoint of ARF was defined as an increase in serum creatinine
      (SCr) of 0.5 mg/dL or 1.0 mg/dL from a baseline SCr of <1.4 mg/dL or >= 1.4
      mg/dL, respectively. RESULTS: In total, 1,472 evaluable doses of ZA were given to
      220 patients. Of these, 184 patients were in the normal group and 36 patients in
      the impaired group. There were 38 patients (20.7%) who developed ARF in the
      normal group versus 7 patients (19.4%) in the impaired group. There was no
      difference in the mean time to the incidence of ARF at 6.1 months in both groups.
      Incidence of ARF based on CrCl (>= 25% decline in CrCl) was similar between
      groups (39.1% vs. 41.7%; p = 0.78). CONCLUSION: The incidence of ARF is similar
      between patients in the normal group and impaired group when the ZA dose is
      renally adjusted.

PMID- 21197551
TI  - A case of an abnormal vein of the hand with characteristics of artery.

PMID- 21197552
TI  - Anesthetic management of noncardiac surgery for patients with single ventricle
      physiology.
AB  - Patients with congenital heart diseases are a growing population, and noncardiac
      surgeries will become an important health care issue. Patients with single
      ventricle physiology are a particularly challenging population who will undergo
      staged, palliative repair toward a final step of Fontan circulation. Although
      Fontan surgery creates a serial circulation in which the ventricle pumps blood to
      the systemic circuit, pulmonary blood flow occurs without a dedicated ventricle.
      Despite progress in outcomes, this abnormal circulation remains associated with
      various co-morbidities such as ventricular dysfunction, arrhythmias, protein
      losing enteropathy, and plastic bronchitis. Health care professionals must
      prepare for these patients to present to noncardiac surgery at any stage of
      intervention, possibly with complications. Given that staged, palliative repair
      has undergone multiple modifications, patients who present for surgery can vary
      in types and timing of the repair. Anesthesiologists who care for them must be
      familiar with perioperative issues to optimize outcomes, especially because
      congenital heart disease is a risk factor for increased mortality for noncardiac
      surgery.

PMID- 21197553
TI  - Clinical features and surgical outcomes of cervical spondylotic myelopathy in
      patients aged 80 years or older: a multi-center retrospective study.
AB  - With the aging of the population in developed countries, spine surgeons have
      recently been more likely to encounter elderly patients in need of treatment.
      This study investigated whether decompression surgery for cervical spondylotic
      myelopathy (CSM) in elderly patients aged 80 years or older would likely be a
      reasonable treatment. We retrospectively reviewed 605 consecutive patients with
      cervical myelopathy who underwent decompression surgery between 2004 and 2008.
      Patients with other conditions that could affect functional status or compression
      factors other than spondylosis were excluded from this study. Of the remaining
      189 patients, 161 with CSM whose condition could be evaluated 6 months after
      surgery were analyzed. The patients were divided into two age groups: 80 years or
      older (Group A, 37 patients) and younger than 80 years of age (Group B, 124
      patients). We evaluated the differences in symptom duration, clinical data,
      involved levels, surgical outcome, comorbidities, and postoperative complications
      between the two groups. The symptom duration was significantly shorter in Group
      A. The average JOA scores preoperatively and 6 months postoperatively were
      significantly lower in Group A; however, there was no significant difference in
      the recovery ratio. There were no significant differences in the percentages of
      patients with comorbidities or those with postoperative complications. Elderly
      patients aged 80 years or older regained approximately 40% of their function
      postoperatively, and the incidence of postoperative complication was similar to
      that in younger patients. Since this age group shows a rapid deterioration after
      onset, prompt decompression surgery is required.

PMID- 21197554
TI  - Absence of infection in pigs inoculated with high-titre recombinant PERV-A/C.
AB  - Porcine endogenous retroviruses (PERVs) represent a risk for xenotransplantation
      using pig cells or organs since they are integrated in the genome of all pigs and
      infect human cells in vitro. Recombinants between PERV-A and PERV-C have been
      described in pigs in vivo and found de novo integrated in the genome of somatic
      cells, but not in the germ line. To study whether PERV-A/C can infect and have a
      pathogenic effect in normal pigs, German landrace pigs were inoculated with high
      titre PERV-A/C. No provirus integration was found in blood cells or in various
      tissues, and no antibody production was observed, indicating the absence of
      infection.

PMID- 21197555
TI  - Passage of low-pathogenic avian influenza (LPAI) viruses mediates rapid genetic
      adaptation of a wild-bird isolate in poultry.
AB  - For a better understanding of evolution of influenza viruses, a chicken-origin
      and wild-bird-origin low-pathogenic avian influenza virus (LPAI) was serially
      passaged in chickens. Sequences of the hemagglutinin (HA) and neuraminidase (NA)
      genes at each passage level were compared to those of the parental virus.
      Multiple mutations occurring early during passage were detected, but these were
      maintained during passages. Interestingly, a number of the observed mutations
      already existed in the parental virus, as indicated by the presence of single
      nucleotide polymorphisms. The greatest numbers of mutations occurred during
      passage of wild-bird-origin LPAI, where a 20-amino-acid deletion in the NA gene
      that was observed during the first passage was maintained during subsequent
      passages. Subsequent experiments showed that this NA deletion was already present
      as a minority population in the parental virus. These results showed that a
      selection process favoring a viral subpopulation had occurred.

PMID- 21197556
TI  - Metal ion binding to anticoagulation factor II from the venom of Agkistrodon
      acutus: stabilization of the structure and regulation of the binding affinity to
      activated coagulation factor X.
AB  - Anticoagulation factor II (ACF II) isolated from the venom of Agkistrodon acutus
      is an activated coagulation factor X (FXa)-binding protein with both
      anticoagulant and hypotensive activities. The thermodynamics of the binding of
      alkaline earth metal ions to ACF II and their effects on the stability of ACF II
      and the binding of ACF II to FXa were investigated by isothermal titration
      calorimetry, fluorescence, differential scanning calorimetry, and surface plasmon
      resonance. The binding of ACF II to FXa does not have an absolute requirement for
      Ca(2+). Mg(2+), Sr(2+), and Ba(2+) can induce the binding of ACF II to FXa. The
      radii of the cations bound in ACF II crucially affect the binding affinity of ACF
      II for cations and the structural stability of ACF II against guanidine
      hydrochloride and thermal denaturation, whereas the radii of cations bound in FXa
      markedly affect the binding affinity between ACF II and FXa. The binding
      affinities of ACF II for cations and the capacities of metal-induced
      stabilization of ACF II follow the same trend: Ca(2+) > Sr(2+) > Ba(2+). The
      metal-induced binding affinities of ACF II for FXa follow the trend Mg(2+) >
      Ca(2+) > Sr(2+) > Ba(2+). Although Mg(2+) shows significantly low binding
      affinity with ACF II, Mg(2+) is the most effective to induce the binding of ACF
      II with FXa. Our observations suggest that in blood the bindings of Ca(2+) in two
      sites of ACF II increase the structural stability of ACF II, but these bindings
      are not essential for the binding of ACF II with FXa, and that the binding of
      Mg(2+) and Ca(2+) to FXa may be essential for the recognition between FXa and ACF
      II. Like Ca(2+), the abundant Mg(2+) in blood also plays an important role in the
      anticoagulation of ACF II.

PMID- 21197557
TI  - The carboxyl terminal of the archaeal nuclease NurA is involved in the
      interaction with single-stranded DNA-binding protein and dimer formation.
AB  - The nuclease NurA is present in all known thermophilic archaea and has been
      implicated to facilitate efficient DNA double-strand break end processing in
      Mre11/Rad50-mediated homologous recombinational repair. To understand the
      structural and functional relationship of this enzyme, we constructed five site
      directed mutants of NurA from Sulfolobus tokodaii (StoNurA), D56A, E114A, D131A,
      Y291A, and H299A, at the conserved motifs, and four terminal deletion mutants,
      StoNurADeltaN (19-331), StoNurADeltaNDeltaC (19-303), StoNurADeltaC (1-281), and
      StoNurADeltaC (1-303), and characterized the proteins biochemically. We found
      that mutation at the acidic residue, D56, E114, D131, or at the basic residue,
      H299, abolishes the nuclease activity, while mutation at the aromatic residue
      Y291 only impairs the activity. Interestingly, by chemical cross-linking assay,
      we found that the mutant Y291A is unable to form stable dimer. Additionally, we
      demonstrated that deletion of the C-terminal amino acid residues 304-331 of
      StoNurA results in loss of the physical and functional interaction with the
      single-stranded DNA-binding protein (StoSSB). These results established that the
      C-terminal conserved aromatic residue Y291 is involved in dimer formation and the
      C-terminal residues 304-331 of NurA are involved in the interaction with single
      stranded DNA-binding protein.

PMID- 21197558
TI  - Purification and characterization of a hyperthermostable Mn-superoxide dismutase
      from Thermus thermophilus HB27.
AB  - Thermostable Mn-dependent catalases are promising enzymes in biotechnological
      applications. In the present study, a Mn-containing superoxide dismutase of the
      hyperthermophilic Thermus thermophilus HB27 had been purified and characterized
      by a two-stage ultrafiltration process after being expressed in E. coli. The
      enzyme was highly stable at 90 degrees C and retained 57% activity after heat
      treatment at 100 degrees C for 1 h. The native form of the enzyme was determined
      as a homotetramer by analytical size exclusion chromatography and sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. The final purified enzyme had an
      isoelectric point of 6.2 and a high alpha-helical content of 70%, consistent with
      the theoretical values. This showed that the purified SOD folded with a
      reasonable secondary structure.

PMID- 21197559
TI  - Different clinical models of CD34 + cells mobilization in patients with
      cardiovascular disease.
AB  - To test the role of necrosis, ischemia or both in bone marrow cells (BMC)
      mobilization in patients with cardiovascular disease. We studied three groups of
      patients: group 1, Iatrogenic Necrosis, with pure necrosis (28 patients
      undergoing transcatheter radiofrequency ablation); group 2, Ischemic Necrosis (30
      patients with myocardial infarction); group 3, Pure Ischemia (24 patients with
      unstable angina). As control groups, we studied 27 patients with stable coronary
      artery disease (CAD), and 20 patients without CAD undergoing angiography for
      valvular diseases or cardiomiopathy. CD34 + cells and cytokines were evaluated
      at: T(0) (baseline), 48 h and 5, 7, 10, 14 days thereafter. We observed a
      significant increase of CD34 + cells at T(3) and T(4) only in Iatrogenic Necrosis
      and Ischemic Necrosis group. The peak of mobilization was observed ten days after
      the necrotic event (2.8 +/- 1.4 vs. 5.9 +/- 1.9 in the group 1, P = 0.03; and 3
      +/- 1.5 vs. 5.6 +/- 2 in the group 2, P = 0.04; respectively). We found a good
      correlation between CD34 + and vascular endothelial growth factor (VEGF) and
      stromal derived factor (SDF-1alpha) peak values (r = 0.77 and r = 0.63,
      respectively). At multivariable analysis, myocardial necrosis (OR 3.5, 95%CI 2.2
      4.2, P < 0.01), VEGF (OR 2, 95%CI 1.1-3, P = 0.01 as above versus below median
      value), and SDF-1alpha (OR 1.6, 95%CI 1.1-2.5, P = 0.02 as above versus below
      median value) emerged as independent predictors of C34 + cells increase.
      Myocardial necrosis with simultaneous elevation of VEGF and SDF-1alpha causes a
      significant CD34 + cells mobilization in patients with cardiovascular disease.

PMID- 21197560
TI  - miR-143 decreases prostate cancer cells proliferation and migration and enhances
      their sensitivity to docetaxel through suppression of KRAS.
AB  - MicroRNAs have been implicated in regulating diverse cellular pathways. Emerging
      evidence indicates that miR-143 plays causal roles in cancer tumorigenesis as a
      tumor suppress gene; however, its role in prostate cancer tumorigenesis remains
      largely unknown. The aims of this study were to verify the effect of miR-143 on
      proliferation and migration abilities of prostate cancer cells. The expression
      level of miR-143 and its target gene KRAS were measured by realtime PCR and
      western blotting, respectively. Effects of miR-143 in cell proliferation,
      migration and chemosensitivity were evaluated by MTT assay, FACS cell cycle
      analysis, colony formation assay, and transwell migratory assay. Our results
      revealed an inverse correlation of expression between miR-143 and KRAS protein in
      prostate cancer samples (Pearson's correlation scatter plots: R = -0.707, P <
      0.05). Moreover, over-expression of miR-143 in prostate cancer cells suppressed
      their proliferation and migration and increased their sensitivity to docetaxel by
      targeting EGFR/RAS/MAPK pathway. These findings suggest that miR-143 plays an
      important role in prostate cancer proliferation, migration and chemosensitivity
      by suppressing KRAS and subsequent inactivation of MAPK pathway, which provides a
      potential development of a new approach for the treatment of prostate cancer.

PMID- 21197561
TI  - sLeX/L-selectin mediates adhesion in vitro implantation model.
AB  - The complex implantation process is initiated by the recognition and adhesion
      between the embryo and uterine endometrial epithelium. The expression and
      interactions between the adhesive molecules from both fetal and maternal sides
      are crucial for the successful implantation. In this study, we aimed to
      investigate the expression and adhesive function of sLeX on the trophoblasts and
      L-selectin on uterine epithelial cells mediated the adhesion at the fetal
      maternal interface, and to further explore whether this adhesion system could
      induce endometrial apoptosis, using in vitro implantation model consisting of the
      human trophoblast cell line (JAR) and human uterine epithelial cell line (RL95
      2). The results showed that sLeX was expressed on JAR cells by indirect
      immunofluorescence staining. After transfection of JAR cells with
      fucosyltransferase VII (FUT7) which is the key enzyme for sLeX synthesis, the
      expression of FUT7 and sLeX synthesis were increased, and the percent adhesion of
      trophoblast cells to RL95-2 cell monolayer was significantly increased (P <
      0.01). L-selectin was strongly expressed but not E- and P-selectin on epithelial
      RL95-2 cells by RT-PCR, Western blot. Blocking L-selectin with specific antibody
      or heparin pretreatment in RL95-2 cells inhibited the adhesion of JAR cells to
      RL95-2 cell monolayer. Furthermore, regulating the expression of sLeX on JAR
      cells or blocking L-selectin on RL95-2 cells could activate the apoptosis of
      uterine epithelial cells. These results suggest the sLeX/L-selectin adhesion
      system at fetal-maternal interface not only mediates the adhesion of embryo to
      uterine epithelium, but also effectively induces the apoptosis in uterine
      epithelium. The study supplies a molecular basis for the elucidation of the
      initial recognition and adhesion during embryo implantation.

PMID- 21197562
TI  - Is effective contraceptive use conceived prenatally in Florida? The association
      between prenatal contraceptive counseling and postpartum contraceptive use.
AB  - The objective of this study is to describe the prevalence of postpartum
      contraceptive use among women experiencing a live birth in Florida in 2004-2005.
      To examine the association between family planning counseling during prenatal
      care visits and the use of effective contraceptive methods among postpartum
      women. Matched data from Florida PRAMS and Vital Statistics were used (n =
      3,962). Weighted logistic regression was used to determine the association
      between prenatal family planning counseling and effective postpartum
      contraceptive use. Odds ratios were adjusted for use of contraception prior to
      pregnancy, well-baby checkup, race, ethnicity, nativity, education, marital
      status, poverty level, stress before or during pregnancy, and parity. Women who
      reported discussing family planning with their prenatal care provider were more
      likely to use effective contraception postpartum (AOR: 1.5, 1.1-2.0) compared to
      women who did not report a discussion. Women who used contraception prior to
      pregnancy (AOR: 2.3, 1.7-3.2) and women who experienced no stress before or
      during pregnancy (AOR: 2.0, 1.2-3.4) were also more likely to use contraception
      in the postpartum period. A significant interaction was identified between family
      planning counseling during prenatal visits and maternal education. Stratum
      specific odds ratios for women who received prenatal family planning counseling
      were significant for women with less than high school education (AOR: 2.5, 1.3
      5.1) and for women with high school education (AOR: 2.0, 1.2-3.4). Women
      reporting family planning counseling during prenatal care were more likely to use
      effective contraception postpartum. While women with high school or less than
      high school education levels benefited from prenatal family planning counseling,
      the greatest benefit was observed for women with less than high school education.
      Integrating family planning counseling into prenatal care may increase the use of
      effective contraceptive methods among postpartum women.

PMID- 21197563
TI  - Psychosocial factors associated with patterns of smoking surrounding pregnancy in
      fragile families.
AB  - Although research has documented factors associated with maternal smoking, we
      need a more in-depth understanding of the risk factors associated with changes in
      smoking behaviors during the postpartum period. We investigate smoking patterns
      during pregnancy and 1 year postpartum as a function of relevant psychosocial
      factors. We use data on 3,522 postpartum mothers from the Fragile Families and
      Child Wellbeing Study to analyze the predictors of smoking among mothers who did
      not smoke during pregnancy but smoked at 1 year postpartum, mothers who smoked
      both during pregnancy and postpartum, and mothers who did not smoke during either
      period. Our covariates are grouped into four categories of risk factors for
      smoking: socioeconomic status, health care, life course and health, and partner
      and social support. Postpartum mothers in our sample were more likely to smoke
      throughout or after their pregnancies if they had only a high school education or
      less, had a household income three or more times below the poverty line, had
      public or no health insurance, breastfed for less than 5 months, were not married
      to the infant's father, if the infant's father currently smoked, and if they
      attended religious services less than once a week. Mental health problems were
      consistently associated with an increased risk of constant and postpartum smoking
      relative to non-smoking. Psychosocial factors play a role in postpartum smoking,
      but they have a stronger effect in predicting smoking that persists throughout
      pregnancy and the first year postpartum.

PMID- 21197564
TI  - Characteristics of anxious and depressed youth seen in two different clinical
      contexts.
AB  - Previous research has revealed that youth seen at community clinics present with
      a higher frequency of externalizing problems and are demographically different
      from youth seen at research clinics. This study extends findings on these
      discrepancies by examining differences between youth at research and community
      clinics meeting criteria for two different primary disorders (anxiety and
      depression). Consistent with prior research, community clinic youth reported
      lower incomes, were more ethnically diverse, and had higher rates of
      externalizing problems compared to research clinic youth, regardless of primary
      diagnosis. Findings are discussed in terms of enhancing dissemination of evidence
      based treatments for internalizing disorders in community settings.

PMID- 21197565
TI  - Advancing a conceptual model of evidence-based practice implementation in public
      service sectors.
AB  - Implementation science is a quickly growing discipline. Lessons learned from
      business and medical settings are being applied but it is unclear how well they
      translate to settings with different historical origins and customs (e.g., public
      mental health, social service, alcohol/drug sectors). The purpose of this paper
      is to propose a multi-level, four phase model of the implementation process
      (i.e., Exploration, Adoption/Preparation, Implementation, Sustainment), derived
      from extant literature, and apply it to public sector services. We highlight
      features of the model likely to be particularly important in each phase, while
      considering the outer and inner contexts (i.e., levels) of public sector service
      systems.

PMID- 21197566
TI  - Trends in return to work of breast cancer survivors.
AB  - Most women interrupt their work activities during the treatment of cancer. This
      study investigated return to work (RTW) after treatment of breast cancer in the
      period from January 2002 to December 2008. ArboNed Occupational Health Service
      records the sickness absence and RTW data of more than one million workers of
      whom approximately 40% are women. Incident cases of sickness absence due to
      breast cancer (ICD-10 code C50) were selected from the ArboNed register.
      Proportions of partial RTW, with 50% of the earnings before sickness absence, and
      full RTW were determined 1 year after diagnosis. Trends in partial RTW and full
      RTW were examined by Chi-square trend analysis. The time to partial RTW and full
      RTW was analysed by Cox regression and stratified by age (<40 years, 40-50 years
      and >50 years). The proportion of partial RTW was stable around 70% from 2002 to
      2008. The proportion of full RTW decreased from 52% in 2002 to 43% in 2008 and
      showed a linear decline in women of all ages. The time to partial RTW and full
      RTW in the years 2003-2008 did not change significantly compared with 2002. In
      the Netherlands, the proportion of employed women who fully resumed working after
      breast cancer within 1 year of diagnosis has decreased since 2002. These results
      warrant more epidemiological research to examine the trends in RTW of breast
      cancer survivors across countries.

PMID- 21197567
TI  - The effects of oncotype DX recurrence scores on chemotherapy utilization in a
      multi-institutional breast cancer cohort.
AB  - The use of clinicopathologic features in decision-making in early stage estrogen
      receptor (ER)-positive breast cancer (BC) may lead to over or under treatment. We
      investigated the effect of the Oncotype Dx (ODX) on chemotherapy (CTX)
      utilization in two cancer centers. 276 cases of node-negative ER-positive BC had
      ODX between 2005 and 2009. Age at diagnosis, tumor size, grade, and progesterone
      receptor (PR) status were abstracted from records and provided to two medical
      oncologists blinded to the ODX score. A recommendation for or against CTX was
      made based on clinicopathologic characteristics. Median age was 55 years. Mean
      tumor size was 1.6 cm. The median 10-year Adjuvant! Online (AO) mortality risk
      was 8. The median Nottingham Prognostic Index (NPI) was 3.3. The median ODX
      recurrence score was 17. Without knowledge of the ODX, oncologists were more
      likely to recommend CTX to younger women (P < 0.0001), women with negative PR
      status (P < 0.0001), higher NPI (P < 0.012), and tumors > 1 cm (P = 0.033). On
      average, CTX recommended patients had larger tumors (2.0 vs. 1.2 cm) and higher
      AO 10-year mortality (11.4 vs. 4.4%). ODX resulted in a change in management for
      38% of women. Of 188 total patients who did not receive CTX, 71 had a
      recommendation favoring CTX by an oncologist blinded to the ODX score. In our
      multi-institutional cohort, the ODX score had a significant impact on the receipt
      of adjuvant CTX and altered management for 38% of women.

PMID- 21197568
TI  - Risk of genome-wide association study newly identified genetic variants for
      breast cancer in Chinese women of Heilongjiang Province.
AB  - Recent genome-wide association studies have identified seven single nucleotide
      polymorphisms (SNPs) associated with breast cancer, but mainly in Europeans. In
      this study, the authors evaluated the effect of these loci on breast cancer and
      its disease characteristics in women from northeast of China, Heilongjiang
      Province. Seven SNPs were successfully genotyped in 492 breast cancer patients
      and 510 healthy controls using the SNaPshot method. The associations between SNPs
      and breast cancer were examined by logistic regression. The associations between
      SNPs and disease characteristics were examined by the chi-square test or one-way
      ANOVA as needed. The authors confirmed the effects of the allele A for rs2046210
      at 6q25 on increased breast cancer risk in the population, with odds ratio 1.417
      (P = 2*10-4). However, no significant association was detected between SNPs from
      TNCR9, LSP1, MAP3K1, 2q35, and 8q24 and breast cancer. Analyses of the disease
      characteristics showed that SNP rs2046210 was associated with age at menopause (P
      = 0.001). MAP3K1 SNP rs889312 and LSP1 SNP rs3817198 were associated with HER2
      status in the patient cohort (P = 0.036 and P = 0.005, respectively). And SNP
      rs3817198 was also associated with the combined status of estrogen receptor,
      progesterone receptor, and HER2 (P = 0.012). SNP rs13281615 was associated with
      age at menarche (P = 0.023), and SNP rs3803662 was associated with average
      duration of breastfeeding (P = 0.036). All other disease characteristics,
      including tumor grade, clinical stage, and the status of estrogen receptor or
      P53, were not significantly associated with any of these variants. These results
      suggested that the rs2046210 was associated with breast cancer in a Northern
      Chinese population, and some SNPs were also associated with breast cancer
      characteristics.

PMID- 21197569
TI  - Post-diagnosis dietary factors and survival after invasive breast cancer.
AB  - Little is known about the effects of diet after breast cancer diagnosis on
      survival. We prospectively examined the relation between post-diagnosis dietary
      factors and breast cancer and all-cause survival in women with a history of
      invasive breast cancer diagnosed between 1987 and 1999 (at ages 20-79 years).
      Diet after breast cancer diagnosis was measured using a 126-item food frequency
      questionnaire. Among 4,441 women without a history of breast cancer recurrence
      prior to completing the questionnaire, 137 subsequently died from breast cancer
      within 7 years of enrollment. Hazard ratios (HR) and 95% confidence intervals
      (CI) were estimated for intake of macronutrients as well as selected
      micronutrients and food groups from Cox proportional hazards regression models.
      After adjustment for factors at diagnosis (age, state of residence, menopausal
      status, smoking, breast cancer stage, alcohol, history of hormone replacement
      therapy), interval between diagnosis and diet assessment, and at follow-up
      (energy intake, breast cancer treatment, body mass index, and physical activity),
      women in the highest compared to lowest quintile of intake of saturated fat and
      trans fat had a significantly higher risk of dying from any cause (HR = 1.41, 95%
      CI = 1.06-1.87, P trend = 0.03) for saturated fat; (HR = 1.78, 95% CI = 1.35
      2.32, P trend = 0.01) for trans fat intake. Associations were similar, though did
      not achieve statistical significance, for breast cancer survival. This study
      suggests that lower intake of saturated and trans fat in the post-diagnosis diet
      is associated with improved survival after breast cancer diagnosis.

PMID- 21197570
TI  - Expression of IGF1R in normal breast tissue and subsequent risk of breast cancer.
AB  - The growth hormone and insulin-like growth factor (IGF) axis plays an essential
      role in the growth and development of the mammary gland. IGF1 and IGF1 receptor
      (IGF1R) may also play a role in the early transformation of mammary cells. Using
      a nested case-control design, the association between IGF1R expression in normal
      breast tissue from benign biopsies and subsequent risk of breast cancer was
      examined in patients enrolled in the Nurses' Health Study. The tissue microarrays
      (TMAs) containing normal terminal duct lobular units (TDLUs) from benign breast
      biopsies were constructed. Immunostains for IGF1R were performed on sections cut
      from the TMAs. A total of 312 women had evaluable IGF1R staining in normal TDLUs;
      75 subsequently developed breast cancer (cases) and 237 did not (controls). The
      epithelial cells in the normal TDLUs were scored for both cytoplasmic and
      membrane staining for IGF1R. Cytoplasmic IGF1R expression was positively
      associated with subsequent risk of breast cancer (OR = 2.47, 95% CI 1.41-4.33).
      Women having TDLU epithelial cells showed little or no membrane expression of
      IGF1R, but those with high levels of cytoplasmic IGF1R were at the highest breast
      cancer risk and were 15 times more likely to develop subsequent breast cancer
      when compared with women who had little or no membrane or cytoplasmic IGF1R
      expression in their TDLU epithelial cells (OR = 15.9, 95% CI 3.6-69.8). In this
      study, it was demonstrated that IGF1R expression patterns in epithelial cells of
      normal TDLUs in benign breast biopsies were associated with an increased risk of
      subsequent breast cancer. Further studies to confirm these findings are
      necessary.

PMID- 21197571
TI  - Cardio-renal syndromes: a systematic approach for consensus definition and
      classification.
AB  - The "Cardio-Renal Syndrome" (CRS) is a disorder of the heart and kidneys whereby
      acute or chronic dysfunction in one organ may induce acute or chronic dysfunction
      of the other. The general definition has been expanded to five subtypes
      reflecting the primacy of organ dysfunction and the time-frame of the syndrome:
      CRS type I: acute worsening of heart function (AHF-ACS) leading to kidney injury
      and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF
      CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of
      kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV:
      chronic kidney disease (CKD) leading to heart injury, disease and/or dysfunction.
      CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction
      of heart and kidney. Different pathophysiological mechanisms are involved in the
      combined dysfunction of heart and kidney in these five types of the syndrome.

PMID- 21197574
TI  - Enhancement of antibody production by the addition of Coenzyme-Q(10).
AB  - Recently, there has been a growing demand for therapeutic monoclonal antibodies
      (MAbs) on the global market. Because therapeutic MAbs are more expensive than low
      molecular-weight drugs, there have been strong demands to lower their production
      costs. Therefore, efficient methods to minimize the cost of goods are currently
      active areas of research. We have screened several enhancers of specific MAb
      production rate (SPR) using a YB2/0 cell line and found that coenzyme-Q(10)
      (CoQ(10)) is a promising enhancer candidate. CoQ(10) is well known as a strong
      antioxidant in the respiratory chain and is used for healthcare and other
      applications. Because CoQ(10) is negligibly water soluble, most studies are
      limited by low concentrations. We added CoQ(10) to a culture medium as dispersed
      nanoparticles at several concentrations (Q-Media) and conducted a fed-batch
      culture. Although the Q-Media had no effect on cumulative viable cell density, it
      enhanced SPR by 29%. In addition, the Q-Media had no effect on the binding or
      cytotoxic activity of MAbs. Q-Media also enhanced SPR with CHO and NS0 cell lines
      by 30%. These observations suggest that CoQ(10) serves as a powerful aid in the
      production of MAbs by enhancing SPR without changing the characteristics of cell
      growth, or adversely affecting the quality or biological activity of MAbs.

PMID- 21197573
TI  - Diversity through semisynthesis: the chemistry and biological activity of
      semisynthetic epothilone derivatives.
AB  - Epothilones are myxobacterial natural products that inhibit human cancer cell
      growth through the stabilization of cellular microtubules (i.e., a "taxol-like"
      mechanism of action). They have proven to be highly productive lead structures
      for anticancer drug discovery, with at least seven epothilone-type agents having
      entered clinical trials in humans over the last several years. SAR studies on
      epothilones have included a large number of fully synthetic analogs and
      semisynthetic derivatives. Previous reviews on the chemistry and biology of
      epothilones have mostly focused on analogs that were obtained by de novo chemical
      synthesis. In contrast, the current review provides a comprehensive overview on
      the chemical transformations that have been investigated for the major
      epothilones A and B as starting materials, and it discusses the biological
      activity of the resulting products. Many semisynthetic epothilone derivatives
      have been found to exhibit potent effects on human cancer cell growth and several
      of these have been advanced to the stage of clinical development. This includes
      the epothilone B lactam ixabepilone (Ixempra((r)), which has been approved by the
      FDA for the treatment of advanced and metastatic breast cancer.

PMID- 21197572
TI  - Chemical biology of histone acetyltransferase natural compounds modulators.
AB  - Histone acetyltransferases (HATs) are a class of epigenetic enzymes crucial for
      chromatin restructuring and transcriptional regulation in eukaryotic cells, thus
      being a promising target for therapeutic development. Nonetheless, differently
      from histone deacetylases (HDACs) inhibitors, there is still paucity of small
      molecule modulators of HAT activity. After a decline during past decade, natural
      products and their derivatives could be once again a valuable tool in the lead
      discovery process and meet such need of Novel Chemical Entities (NCEs). In this
      review, we will provide a comprehensive summary on the discovery of small
      molecule HAT modulators from naturally occurring molecular scaffolds.

PMID- 21197575
TI  - Effects of artemisinin in broiler chickens following chronic oral intake.
AB  - Artemisinin has been used for centuries to treat malaria, intestinal tract
      helminthosis, diarrhea, and used as an antipyretic and sedative agent, but the
      usage in veterinary medicine is a new field. Recently, it has been used
      successfully to control experimental poultry coccidiosis. The present study aimed
      to determine the effects of different doses of artemisinin in broiler chickens
      with chronic usage. Sixty birds divided into one control and four treatment
      groups that fed rations mixed with artemisinin at doses of 17, 34, 68, and 136
      ppm for 36 days. During the experiment, birds showed no clinical signs except
      anemia. In microscopic examinations, heart, lung, and spleen had no lesion, but
      liver, kidney, and brain showed various lesions. Degenerative lesions like
      intracytoplasmic eosinophilic inclusions were seen in both kidney and liver but
      fatty change was seen only in liver. There was no relationship between severity
      of the liver lesions and drug dosage. Central chromatolysis, scattered neuronal
      necrosis, and mild spongy changes were observed in five regions of the brain that
      were chosen for sectioning (motor cortex, cerebellar nuclei, midbrain nuclei, and
      hindbrain nuclei at two separate levels). Severity of lesions in brain was dose
      dependent, and cerebral cortex was the most vulnerable area. Haematologic tests
      showed lower values for hematocrit and red blood cell count dose-dependently. In
      conclusion, artemisinin is a promising drug for prevention and control of
      coccidiosis in broiler chickens and its side effects are not too much serious
      especially at therapeutic doses.

PMID- 21197576
TI  - Plant species used in traditional smallholder dairy processing in East Shoa,
      Ethiopia.
AB  - Plant species used in traditional dairy processing were studied in three
      districts (Bosset, Ada, and Gimbichu) in Eastern Shoa, Ethiopia, from October
      2007 to March 2008. A total of 300 smallholders were interviewed using semi
      structured questionnaires, and three focus group discussions were conducted,
      followed by plants specimen collection and identification. A total of 36 plant
      species, falling under 24 plant families, were identified. Nearly half of the
      identified plant species had more than one use types. Eleven plant species
      were/are used for washing (scrubbing) dairy utensils, ten plant species for
      smoking dairy utensils, 12 plant species in butter making, 15 plant species in
      ghee making, and five plant species for packaging (wrapping) butter and cheese.
      The plant species that had the highest overall citations from each use category
      were Ocimum hardiense, Olea europaea subspecies africana, Trachyspermum copticum,
      Curcuma longa, and Croton macrostachyus. The plant species used in the three
      study districts, representing different agro ecologies, showed some similarities,
      but levels of uses differed significantly (P < 0.05). Higher informant citations
      might indicate their better efficacy, however need to be further investigated to
      determine their effects on milk and milk product quality and to make sure that
      they are innocuous to human and animal health. Finally, as the present study
      tried to document natural products used in traditional dairy processing, it could
      be considered as part of the global efforts aimed at promoting organic food
      production.

PMID- 21197577
TI  - Ovariectomy causes immunosenescence and oxi-inflamm-ageing in peritoneal
      leukocytes of aged female mice similar to that in aged males.
AB  - Immunosenescence involves age-associated restructuring changes of innate and
      adaptative immune functions. We have suggested that these changes of the immune
      system participate in the rate of ageing through modulating oxi-inflamm-ageing.
      Thus, age-related changes in the immune system can be biological age markers and
      predictors of longevity. Gender differences in oxidation status and immune
      functions have been observed in rats, with males showing higher oxidation and
      immunosenescence than females of the same age. Oestrogens are sex hormones that
      actively participate in modulating the mammalian immune function and, therefore,
      the age-related impairment of the immune response is drastically accelerated in
      females during the menopausal transition. Ovariectomy in rodents constitutes a
      good model for mimicking human oestrogen loss and thus the menopausal situation.
      Recently, we have shown the deleterious effects of oestrogen loss on several
      functions of leukocytes from immune organs in rats and mice. In addition,
      ovariectomised rats show similar levels in these immune functions to those in
      males. The present work studied several functions as well as inflammatory and
      oxidative stress parameters in mouse peritoneal macrophages and lymphocytes from
      old sham and ovariectomised females, as well as in males of the same age. In
      general, the results show that females, which have a higher immune response and a
      lower oxidation and inflammation than males, appear similar to males in the
      parameters studied when they have lost oestrogens by ovariectomy. Thus, these
      data support the positive role of oestrogens in the immune function through the
      ageing process.

PMID- 21197578
TI  - Rapid cold-hardening blocks cold-induced apoptosis by inhibiting the activation
      of pro-caspases in the flesh fly Sarcophaga crassipalpis.
AB  - Apoptosis plays important roles in the selective elimination of sub-lethally
      damaged cells due to various environmental stresses. The rapid cold-hardening
      (RCH) response protects insects from the otherwise lethal consequences of injury
      due to cold-shock. We recently demonstrated that cold shock induces apoptotic
      cell death in insects and that RCH functions to specifically block cold-shock
      induced apoptosis. In the present study we used isolated fat body, midgut,
      muscle, and Malpighian tubules from adult flesh flies Sarcophaga crassipalpis to
      test the following hypotheses: (1) cold-induced apoptosis varies among different
      tissues and (2) RCH blocks the apoptotic pathway by preventing the activation of
      pro-caspases. Cold-shock induced substantial amounts of apoptotic cell death that
      matched with tissue damage as determined using vital dyes. RCH treatment
      significantly reduced apoptotic cell death in all tested tissues. Caspase-3
      (executioner) activity was 2-3 times higher in the cold- and heat-shocked groups
      than in control and RCH groups. Likewise, the activity of caspase-9 (initiator)
      showed a similar trend as for caspase-3 in all tissues but midgut. In addition,
      cold-shock and heat-shock treatments also increased caspase-2 activity 2-3 folds
      in both soluble and membrane fractions of fat body and muscle extracts compared
      to controls.

PMID- 21197579
TI  - Polyclonal rabbit anti-murine plasmacytoma cell globulins induce myeloma cells
      apoptosis and inhibit tumour growth in mice.
AB  - Multiple myelomas (MMs) are etiologically heterogeneous and there are limited
      treatment options; indeed, current monoclonal antibody therapies have had limited
      success, so more effective antibodies are urgently needed. Polyclonal antibodies
      are a possible alternative because they target multiple antigens simultaneously.
      In this study, we produced polyclonal rabbit anti-murine plasmacytoma cell
      immunoglobulin (PAb) by immunizing rabbits with the murine plasmacytoma cell line
      MPC-11. The isolated PAb bound to plasma surface antigens in several MM cell
      lines, inhibited their proliferation as revealed by MTT assay, and induce
      apoptosis as indicated by flow cytometry, microscopic observation of apoptotic
      changes in morphology, and DNA fragmentation on agarose gels. The cytotoxicity of
      PAb on MPC-11 cell lines was both dose-dependent and time-dependent; PAb exerted
      a 50% inhibitory effect on MPC-11 cell viability at a concentration of 200 ug/ml
      in 48 h. Flow cytometry demonstrated that PAb treatment significantly increased
      the number of apoptotic cells (48.1%) compared with control IgG (8.3%). Apoptosis
      triggered by PAb was confirmed by activation of caspase-3, -8, and -9. Serial
      intravenous or intraperitoneal injections of PAb inhibited tumour growth and
      prolonged survival in mice bearing murine plasmacytoma, while TUNEL assay
      demonstrated that PAb induced statistically significant apoptosis (P < 0.05)
      compared to control treatments. We conclude that PAb is an effective agent for in
      vitro and in vivo induction of apoptosis in multiple myeloma and that exploratory
      clinical trials may be warranted.

PMID- 21197580
TI  - Correlation between high density lipoprotein-cholesterol and remodeling index in
      patients with coronary artery disease: IDEAS (IVUS diagnostic evaluation of
      atherosclerosis in Singapore)-HDL study.
AB  - Serum level of high density lipoprotein (HDL)-cholesterol is associated with risk
      of coronary artery disease. We correlated the serum level of cholesterol with
      coronary artery remodeling index of patients with coronary artery disease. A
      total of 120 patients with de novo lesions located in native coronary artery were
      studied. Remodeling index was based on intravascular ultrasound (IVUS)
      interrogation of the lesions using the static approach, and was defined as
      external elastic membrane (EEM) area at lesion/average EEM area at proximal and
      distal reference segments. The average remodeling index was 0.9 (SD: 0.2). The
      remodeling index was not associated with any of the demographic and coronary risk
      factors. Stable angina was associated with a low remodeling index. Remodeling
      index correlated with white blood cell count and HDL-cholesterol, but not with
      total cholesterol, LDL-cholesterol and triglyceride. In the multiple linear
      regression analysis, HDL-cholesterol and procedure indication were the only 2
      significant predictors of remodeling index. An increase of 1 mg/dL of HDL
      cholesterol resulted in a decrease of 0.003 (95% CI: 0.0001, 0.007; P = 0.046) in
      remodeling index, after adjusting for procedural indications. When stratified
      according to diabetic status, the negative correlation persisted in non-diabetic
      (P = 0.023), but not in diabetic, patients (P = 0.707). We found a negative
      correlation between HDL-cholesterol level and remodeling index. Diabetic status
      may have an influence on the observed relationship.

PMID- 21197581
TI  - First environmental isolations of Cryptococcus neoformans and Cryptococcus gattii
      in Tunisia and review of published studies on environmental isolations in Africa.
AB  - Cryptococcus neoformans and Cryptococcus gattii are pathogenic yeasts that cause
      cryptococcosis. These fungi were commonly associated with pigeon droppings and
      plant materials. The habitat of these pathogens has not been yet studied in
      Tunisia, although the ecology of these yeasts must be elucidated in order to
      establish surveillance programs and to prevent infections. The aim of this survey
      was to recover C. neoformans and C. gattii environmental isolates from pigeon
      droppings and plant materials in different areas of Sfax region, Tunisia. Nine
      hundred and fifty samples from leaves, wood, flowers, fruits and soil around
      trunk bases of 40 almond (Prunus dulcis) and 60 eucalyptus trees were collected
      as well as 250 pigeon droppings samples from different sites: buildings (n =
      150), houses (n = 50) and zoo (n = 50). The identification of Cryptococcus
      neoformans complex was confirmed using the ID32C auxanogram panel (BioMerieux,
      Marcy l'Etoile, France); species were determined by multiplex PCR using the CN70
      and CN49 primers, and mating type was determined by PCR. C. neoformans was
      recovered from 26 specimens of pigeon droppings (10.4%). This yeast was obtained
      more frequently from dry droppings (9.2%) than from moist droppings (1.2%). The
      mating type was determined. All the 31 environmental strains of C. neoformans and
      C. gattii were MATalpha. Out of 700 samples tested from 100 trees, only 5
      isolates of Cryptococcus neoformans species complex were recovered (0.6%), two
      isolates of C. gattii and one isolate of C. neoformans were recovered from the
      wood of E. camaldulensis trees, and only two isolates of C. gattii were recovered
      from the wood of almond trees (Prunus dulcis Mill. var. zaaf and var. achek).
      These two Tunisian almond tree varieties were recorded for the first time in
      Africa as hosts for C. gattii. These results add new information to the ecology
      and epidemiology of C. neoformans species complex in Tunisia.

PMID- 21197582
TI  - A new test of the construct validity of the CarerQol instrument: measuring the
      impact of informal care giving.
AB  - PURPOSE: Most economic evaluations of health care programmes do not consider the
      effects of informal care, while this could lead to suboptimal policy decisions.
      This study investigates the construct validity of the CarerQol instrument, which
      measures and values carer effects, in a new population of informal caregivers.
      METHODS: A questionnaire was distributed by mail (n = 1,100, net response rate =
      21%) to regional informal care support centers throughout the Netherlands. Two
      types of construct validity, i.e., convergent and clinical validity, have been
      analyzed. Convergent validity was assessed with Spearman's correlation
      coefficients and multivariate correlation between the burden dimensions (CarerQol
      7D) and the valuation component (CarerQol-VAS) of the CarerQol. Additionally,
      convergent validity was analyzed with Spearman's correlation coefficients between
      the CarerQol and other measures of subjective caregiver burden (SRB, PU).
      Clinical validity was evaluated with multivariate correlation between CarerQol
      VAS and CarerQol-7D, characteristics of caregivers, care recipients and care
      situation among the whole sample of caregivers and subgroups. RESULTS: The
      positive (negative) dimensions of CarerQol-7D were positively (negatively)
      related to CarerQol-VAS, and almost all had moderate strength of convergent
      validity. CarerQol-VAS was positively associated with PU and negatively with SRB.
      The CarerQol-VAS reflects differences in important background characteristics of
      informal care: type of relationship, age of the care recipient and duration of
      care giving were associated with higher CarerQol-VAS scores. These results
      confirmed earlier tests of the construct validity of the CarerQol. Furthermore,
      the dimensions of CarerQol-7D significantly explained differences in CarerQol-VAS
      scores among subgroups of carers. CONCLUSION: Notwithstanding the limitations of
      our study, such as the low response rate, this study shows that the CarerQol
      provides a valid means to measure carer effects for use in economic evaluations.
      Future research should derive a valuation set for the CarerQol and further
      address the instrument's content validity, sensitivity and reliability.

PMID- 21197583
TI  - Local antibiotic delivery with demineralized bone matrix.
AB  - A method of care for these infected nonunions is prolonged intravenous systemic
      antibiotic treatment and implantation of methyl methacrylate antibiotic carrier
      beads to delivery high local doses of antibiotics. This method requires a second
      surgery to remove the beads once the infection has cleared. Recent studies have
      investigated the use of biodegradable materials that have been impregnated with
      antibiotics as tools to treat bone infections. In the present study, human
      demineralized bone matrix (DBM) was investigated for its ability to be loaded
      with an antibiotic. The data presented herein demonstrates that this
      osteoinductive and biodegradable material can be loaded with gentamicin and
      release clinically relevant levels of the drug for at least 13 days in vitro.
      This study also demonstrates that the antibiotic loaded onto the graft has no
      adverse effects on the osteoinductive nature of the DBM as measured in vitro and
      in vivo. This bone void filler may represent a promising option for local
      antibiotic delivery in orthopedic applications.

PMID- 21197585
TI  - Re: Axillary staging in the neoadjuvant setting.

PMID- 21197586
TI  - Palm olein and olive oil cause a higher increase in postprandial lipemia compared
      with lard but had no effect on plasma glucose, insulin and adipocytokines.
AB  - Postprandial lipemia impairs insulin sensitivity and triggers the pro
      inflammatory state which may lead to the progression of cardiovascular diseases.
      A randomized, crossover single-blind study (n = 10 healthy men) was designed to
      compare the effects of a high-fat load (50 g fat), rich in palmitic acid from
      both plant (palm olein) or animal source (lard) versus an oleic acid-rich fat
      (virgin olive oil) on lipemia, plasma glucose, insulin and adipocytokines. Serum
      triacylglycerol (TAG) concentrations were significantly lower after the lard meal
      than after the olive oil and palm olein meals (meal effect P = 0.003; time effect
      P < 0.001). The greater reduction in the plasma non-esterified free fatty acids
      levels in the lard group compared to the olive oil meal was mirrored by the
      changes observed for serum TAG levels (P < 0.05). The magnitude of response for
      plasma glucose, insulin and adipocytokines [interleukin-6 (IL-6), tumor necrosis
      factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and leptin] were not
      altered by the type of dietary fats. A significant difference in plasma IL-1beta
      was found over time following the three high fat loads (time effect P = 0.036).
      The physical characteristics and changes in TAG structure of lard may contribute
      to the smaller increase in postprandial lipemia compared with palm olein. A high
      fat load but not the type of fats influences concentrations of plasma IL-1beta
      over time but had no effect on other pro-inflammatory markers tested in the
      postprandial state.

PMID- 21197587
TI  - A study of pre-operative type and screen in breast surgery: improved efficiency
      and cost saving.
AB  - INTRODUCTION: Patients undergoing major breast surgery have an almost negligible
      need for blood transfusions. However, type and screen requests are still
      routinely performed. This represents an inefficient utilization of resources and
      unnecessary workload for laboratory staff. The aim of this study was to ascertain
      whether pre-operative blood typing is justified in patients undergoing surgical
      procedures with an intermediate transfusion probability. METHODS: A retrospective
      analysis of all patients undergoing a mastectomy and axillary clearance, with or
      without breast reconstruction in the last 2 years was undertaken. The number of
      group and hold and cross-match samples that were performed were identified and
      compared to the number of patients requiring a blood transfusion. The overall
      cost of routine pre-operative blood typing was analysed. RESULTS: A total of 229
      patients were identified. Of these, a group and hold was performed on 192 (83.8%)
      patients. Cross-matching was undertaken in thirty-one patients (13.5%). In total,
      five patients (2.1%) required transfusion. No patient was transfused intra
      operatively. The overall cost of routine group and hold blood requests was 1,920
      euros and of pre-operative cross-matching was 465 euros. Forty-seven units of
      blood was returned unused to the blood transfusion service at an estimated cost
      of 23,500 euros. CONCLUSION: The need for routine group and hold blood requests
      is not justified for patients undergoing elective breast surgery and represents a
      waste of clinical resources. A more targeted approach will not only reduce the
      demand on blood products but also reduce the associated costs to blood
      transfusion services.

PMID- 21197588
TI  - An adeno-associated virus vector efficiently and specifically transduces mouse
      skeletal muscle.
AB  - Expression of a therapeutic gene in the skeletal muscle is a practical strategy
      to compensate a patients' insufficient circulating factor. Its clinical
      application requires a muscle-targeting vector capable of inducing a continuous
      high-level transgene expression. We modified an adeno-associated virus serotype 2
      (AAV2) vector expressing luciferase from the mouse muscle creatine kinase gene
      promoter-enhancer (Ckm). First, AAVS1 insulator was inserted into the vector
      genome for transcriptional enhancement. This increased transduction of mouse
      quadriceps muscle by 11-fold at 4 weeks after intramuscular injection. Second,
      two capsid modifications were combined (21F capsid): incorporation of a segment
      of AAV1 capsid to produce a hybrid capsid and substitution of a tyrosine with a
      phenylalanine. Use of 21F capsid increased muscle transduction further by 18
      fold, resulting in 200-fold higher efficacy than that of the unmodified vector.
      Compared with a vector having human elongation factor 1alpha promoter which
      showed similar efficacy in the muscle, this vector having Ckm transduced non
      muscle organs less efficiently after intravenous administration. The AAV2 vector
      composed of the modified genome and capsid provides a backbone to develop a
      clinical vector expressing a therapeutic gene in the muscle.

PMID- 21197589
TI  - Ribosome display selection of a murine IgG1 Fab binding affibody molecule
      allowing species selective recovery of monoclonal antibodies.
AB  - Affinity reagents recognizing constant parts of antibody molecules are invaluable
      tools in immunotechnology applications, including purification, immobilization,
      and detection of immunoglobulins. In this article, murine IgG1, the primary
      isotype of monoclonal antibodies (mAbs) was used as target for selection of novel
      binders from a combinatorial ribosome display (RD) library of 1011 affibody
      molecules. Four rounds of selection using three different mouse IgG1 mAbs as
      alternating targets resulted in the identification of binders with broad mIgG1
      recognition and dissociation constants (K(D)) in the low nanomolar to low
      micromolar range. For one of the binders, denoted Z(mab25), competition in
      binding to full length mIgG1 by a streptococcal protein G (SPG) fragment and
      selective affinity capture of mouse IgG1 Fab fragments after papain cleavage of a
      full mAb suggest that an epitope functionally overlapping with the SPG-binding
      site in the CH1 domain of mouse IgG1 had been addressed. Interestingly, biosensor
      based binding experiments showed that neither human IgG1 nor bovine Ig, the
      latter present in fetal bovine serum (FBS) was recognized by Z(mab25). This
      selective binding profile towards murine IgG1 was successfully exploited in
      species selective recovery of two different mouse mAbs from complex samples
      containing FBS, resembling a hybridoma culture supernatant.

PMID- 21197590
TI  - 1H, 13C, and 15N backbone, side-chain, and heme chemical shift assignments for
      oxidized and reduced forms of the monoheme c-type cytochrome ApcA isolated from
      the acidophilic metal-reducing bacterium Acidiphilium cryptum.
AB  - We report the (1)H, (13)C, and (15)N chemical shift assignments of both oxidized
      and reduced forms of an abundant periplasmic c-type cytochrome, designated ApcA,
      isolated from the acidophilic gram-negative facultatively anaerobic metal
      reducing alphaproteobacterium Acidiphilium cryptum. These resonance assignments
      prove that ApcA is a monoheme cytochrome c (2) and the product of the Acry_2099
      gene. An absence of resonance peaks in the NMR spectra for the 21N-terminal
      residues suggests that a predicted N-terminal signal sequence is cleaved. We also
      describe the preparation and purification of the protein in labeled form from
      laboratory cultures of A. cryptum growing on (13)C- and (15)N- labeled
      substrates.

PMID- 21197591
TI  - A small intraneural epithelioid malignant peripheral nerve sheath tumour of the
      median nerve simulating a benign lesion: description of a case and review of the
      literature.
AB  - The epithelioid variant of malignant peripheral nerve sheath tumours (MPNSTs) is
      a very rare malignancy. We describe the case of a 30-year-old man complaining of
      acute pain in his right elbow, mild distal paraesthesias, and some motor
      deficiencies. He was discovered as having a small fusiform swelling of the median
      nerve. In view of its very small size, shape, and nonspecific MRI signal, it had
      initially suggested a benign lesion. The diagnosis of epithelioid MPNST was made
      only at the histopathological examination. This malignant neoplasm recurred
      locally fourteen months after surgery. In addition to describe the above very
      rare case, we have reviewed the literature on epithelioid MPNSTs clearly
      involving deep major nerve trunks. This case serves as a warning that, even in
      major nerve trunks, tiny lesions may in reality be early intraneural MPNSTs
      which, due to their deep location, must be treated adequately with wide margin
      surgery since the resection margin status represents one of the major parameters
      influencing the local control of disease and its clinical outcome.

PMID- 21197592
TI  - A rare cause of Fever, hepatosplenomegaly, and thrombocytopenia: hepatosplenic
      gamma/delta T-cell lymphoma.

PMID- 21197593
TI  - The diagnostic value of evaluating the maximum velocity of blood flow in the
      uterine arteries of women with postmenopausal bleeding.
AB  - PURPOSE: The aim was to evaluate the utility of ultrasonographic examinations,
      such as the Doppler technique, in diagnosing women with postmenopausal bleeding.
      METHODS: Specifically, maximum end-diastolic velocity of blood flow (MEDV), time
      averaged maximum velocity of blood flow (TAMXV) and peak systolic velocity of
      blood flow (PSV) were evaluated. Data were obtained and analyzed from a group of
      100 female patients diagnosed and treated because of abnormal bleeding from the
      genitals in the Gynecological-Obstetrics Clinical Hospital of Poznan University
      of Medical Sciences. The following packages were used for statistic analyses:
      STATISTICA v 7.1 (StatSoft, Inc. 2005), StatXACT v.5.0.3, CYTEL SOFTWARE
      CORPORATION and Analyse-it Software v.1.68. RESULTS: The parameters evaluated
      were highest in the carcinoma group, lower when proliferation was diagnosed and
      the lowest in the control group. CONCLUSIONS: Transvaginal ultrasonography
      diagnostics using the Doppler technique was found to play an important role in
      the diagnostic process of pathologies within the endometrium.

PMID- 21197594
TI  - A structured questionnaire improves preoperative assessment of endometriosis
      patients: a retrospective analysis and prospective trial.
AB  - PURPOSE: To determine whether a structured questionnaire can improve preoperative
      assessment of patients with endometriosis. METHODS: Hospital records for patients
      with endometriosis were evaluated retrospectively to determine the completeness
      of information. A structured electronic questionnaire was developed and used to
      assess preoperatively patients with suspected or proved endometriosis. Data from
      both assessments were compared. RESULTS: Data analysed retrospectively showed
      that there were valid answers for 89.2% of questions on a standard patient
      history template, but information was available for only 46.3% of parameters
      considered specific to endometriosis. Data from 69 patients investigated by
      structured electronic questionnaire gave improved rates of 90.3% for standard
      patient history items and 88.5% for endometriosis-specific parameters.
      Significant improvement in valid answers was achieved in 66.7%. CONCLUSIONS: A
      structured questionnaire improved the documentation of endometriosis-specific
      parameters. Further studies are needed to ensure that it enhances the
      effectiveness of preoperative counselling and decisions about surgery.

PMID- 21197595
TI  - Effect of pre-pregnancy body mass index on adverse pregnancy outcome in north of
      China.
AB  - PURPOSE: To investigate the effect of pre-pregnancy BMI on adverse maternal and
      neonatal outcomes in pregnancy women of northern China. METHODS: We conducted a
      retrospective population-based cohort study of 5,047 singleton nulliparous
      pregnancies. The subjects were categorized into four groups by BMI-underweight
      (BMI < 18.5 kg/m(2)), normal (BMI 18.5-24 kg/m(2)), overweight (BMI 24-28
      kg/m(2)) and obese (BMI >= 28 kg/m(2)). Logistic regression was used to adjust
      the potential confounder. Maternal and neonatal outcomes were evaluated with
      relative risks and 95% confidence intervals. RESULTS: 11.5, 63.4, 18.3, and 6.8%
      of the subjects were underweight, normal BMI, overweight and obese, respectively.
      Compared with women of normal BMI, the risk of the following outcomes was
      significantly increased in overweight and obese women and expressed as [adjusted
      RR (95% confidence interval)] respectively: pre-eclampsia [2.99 (2.21-4.06), 5.68
      (3.97-8.11)]; gestational diabetes [2.49 (1.82-3.39), 4.35 (3.00-6.31)];
      premature rupture of the membranes [1.64 (1.20-2.23), 1.73 (1.11-2.72)];
      abruption placentae [1.84 (1.19-2.87), 2.79 (1.60-4.83)]; cesarian section [1.47
      (1.27-1.70), 2.51 (1.97-3.20)]; postpartum hemorrhage [2.31 (1.51-3.54), 3.73
      (2.37-5.04)]; perineal rupture [2.89 (1.44-5.81), 3.36 (1.55-7.30)]; large-for
      gestational age [1.46 (1.02-2.08), 1.91 (1.17-3.10)]. However, anemia (2.54, 1.15
      5.63), small-for-gestational age (1.67, 1.07-2.61) were significantly more common
      in the underweight group. CONCLUSIONS: The prevalence of overweight and obesity
      in women of northern China is much lower than in the Caucasian population or
      Chinese in Hong Kong. The increased maternal BMI is associated with many adverse
      pregnancy outcomes and its risk increases with the degree of obesity. Maternal
      underweight has a protective effect although increases the risk of having small
      for-gestational age baby and anemia.

PMID- 21197597
TI  - Differential antioxidative responses to dehydration-induced oxidative stress in
      core set of foxtail millet cultivars [Setaria italica (L.)].
AB  - Foxtail millet (Setaria italica L.) known as a relatively drought-tolerant crop
      across the world is grown in arid and semi-arid regions. To the best of our
      knowledge, no systematic study on drought tolerance screening of foxtail millet
      germplasm being a drought-tolerant crop has been reported so far. To explore
      genetic diversity of drought-induced oxidative stress tolerance in foxtail
      millet, we employed lipid peroxidation measure to assess membrane integrity under
      stress as biochemical marker to screen 107 cultivars and classified the genotypes
      as highly tolerant, tolerant, sensitive, and highly sensitive. From this
      comprehensive screening, four cultivars showing differential response to
      dehydration tolerance were selected to understand the physiological and
      biochemical basis of tolerance mechanisms. The dehydration-tolerant cultivars (IC
      403579 and Prasad) showed considerably lower levels of lipid peroxidation and
      electrolyte leakage as compared with dehydration-sensitive cultivars (IC-480117
      and Lepakshi), indicating better cell membrane integrity in tolerant cultivars.
      Correspondingly, tolerant genotypes maintained higher activity of catalase (EC
      1.11.1.6), ascorbate peroxidase (APX; EC 1.11.1.11), and glutathione reductase
      (GR; EC 1.6.4.2) across different time-course period of polyethylene glycol (PEG)
      treatments in comparison to sensitive ones. The above biochemical results were
      further validated through quantitative real-time PCR analysis of APX and GR,
      whose transcripts were substantially induced by PEG treatments in tolerant
      cultivars. These results suggest that tolerant cultivars possess wider array of
      antioxidant machinery with efficient ascorbate-glutathione pathway to cope with
      drought-induced oxidative stress.

PMID- 21197598
TI  - Difficulty accessing syringes mediates the relationship between methamphetamine
      use and syringe sharing among young injection drug users.
AB  - Injection drug users (IDU) who use methamphetamine (MA) are at an increased risk
      of HIV infection due to engagement in injection-related risk behavior including
      syringe sharing. In this cohort study of young IDU aged 18-30, we investigated
      the relationship between injection MA use and syringe sharing, and whether
      difficulty accessing sterile syringes mediated this association. Behavioral
      questionnaires were completed by 384 IDU in Vancouver, Canada between October
      2005 and May 2008. Generalized estimating equations were used to estimate direct
      and indirect effects. The median age of participants was 24 (IQR: 22-27) and 214
      (55.7%) were male. Injecting MA was independently associated with syringe
      sharing. Mediation analyses revealed that difficulty accessing sterile syringes
      partially mediated the association between injecting MA and syringe sharing.
      Interventions to reduce syringe sharing among young methamphetamine injectors
      must address social and structural barriers to accessing HIV prevention programs.

PMID- 21197596
TI  - The impact of inflammation on bone mass in children.
AB  - Bone is a dynamic tissue. Skeletal bone integrity is maintained through bone
      modeling and remodeling. The mechanisms underlying this bone mass regulation are
      complex and interrelated. An imbalance in the regulation of bone remodeling
      through bone resorption and bone formation results in bone loss. Chronic
      inflammation influences bone mass regulation. Inflammation-related bone disorders
      share many common mechanisms of bone loss. These mechanisms are ultimately
      mediated through the uncoupling of bone remodeling. Cachexia, physical
      inactivity, pro-inflammatory cytokines, as well as iatrogenic factors related to
      effects of immunosuppression are some of the common mechanisms. Recently,
      cytokine signaling through the central nervous system has been investigated for
      its potential role in bone mass dysregulation in inflammatory conditions. Growing
      research on the molecular mechanisms involved in inflammation-induced bone loss
      may lead to more selective therapeutic targeting of these pathological signaling
      pathways.

PMID- 21197599
TI  - Conversations with mothers: exploring reasons for prevention of mother-to-child
      transmission (PMTCT) failures in the era of programmatic scale-up in Soweto,
      South Africa.
AB  - Reasons for incident cases of vertical HIV transmission in the era of free access
      to PMTCT in South Africa were investigated. This mixed-methods study was
      conducted in Soweto, South Africa from June-August, 2009. Birthmothers of HIV
      infected infants born after 1 December 2008 were eligible. All participants
      completed an interviewer-administered questionnaire. Women also participated in a
      focus group (n = 10) or individual structured interview (n = 35). Mean age of
      participants (n = 45) was 28.7 years (SD = 5.4). Major findings are: (i) failure
      of per-guideline prescription of ARV strategies for infants (31%) and/or mothers
      (57%); (ii) maternal refusal of treatment (n = 5); (iii) preterm delivery (31%);
      (iv) delayed ANC attendance because of facility-related barriers and maternal
      apprehension around HIV testing; (v) fear of stigma; (vi) maternal difficulty
      with administering infant AZT (n = 9) and (vii) maternal confusion about infant
      feeding. A variety of individual, social, and structural factors must be
      addressed to optimize PMTCT service delivery in South Africa.

PMID- 21197600
TI  - Disclosure of HIV status to sex partners among HIV-infected men and women in Cape
      Town, South Africa.
AB  - This study examines factors influencing HIV sero-status disclosure to sex
      partners among a sample of 630 HIV-infected men and women with recent sexual
      contact attending anti-retroviral therapy (ART) clinics in Cape Town, South
      Africa, with a focus on sex partner type, HIV-related stigma, and ART as
      potential correlates. About 20% of the sample had not disclosed their HIV status
      to their most recent sex partners. HIV disclosure to sex partner was more likely
      among participants who had a steady sex partner [Adjusted odds ratio (AOR) = 2.7;
      95% CI: 1.6-4.6], had a partner with known-HIV status [AOR = 7.8; 95% CI: 3.2
      18.7]; perceived less stigma [AOR = 1.9; 95% CI: 1.2-2.9]; and were on ART [AOR =
      1.6; 95% CI: 1.1-2.3]. Stratified analyses by the type of sex partner further
      reveals that stigma and ART were significantly associated with HIV disclosure
      within steady relationships but were not significant correlates of HIV disclosure
      with casual sex partners. The findings support a positive prevention strategy
      that emphasizes increased access to ART, and behavioral interventions to reduce
      casual sex partnerships for persons who are HIV-positive. Mitigating the
      influence of HIV stigma on HIV status disclosure particularly within steady sex
      partnerships is also important and may be accomplished through individual and
      couple counseling.

PMID- 21197601
TI  - A semi-quantitative approach to GMO risk-benefit analysis.
AB  - In many countries there are increasing calls for the benefits of genetically
      modified organisms (GMOs) to be considered as well as the risks, and for a risk
      benefit analysis to form an integral part of GMO regulatory frameworks. This
      trend represents a shift away from the strict emphasis on risks, which is
      encapsulated in the Precautionary Principle that forms the basis for the
      Cartagena Protocol on Biosafety, and which is reflected in the national
      legislation of many countries. The introduction of risk-benefit analysis of GMOs
      would be facilitated if clear methodologies were available to support the
      analysis. Up to now, methodologies for risk-benefit analysis that would be
      applicable to the introduction of GMOs have not been well defined. This paper
      describes a relatively simple semi-quantitative methodology that could be easily
      applied as a decision support tool, giving particular consideration to the needs
      of regulators in developing countries where there are limited resources and
      experience. The application of the methodology is demonstrated using the release
      of an insect resistant maize variety in South Africa as a case study. The
      applicability of the method in the South African regulatory system is also
      discussed, as an example of what might be involved in introducing changes into an
      existing regulatory process.

PMID- 21197602
TI  - Identification of candidate genes associated with senescence in durum wheat
      (Triticum turgidum subsp. durum) using cDNA-AFLP.
AB  - Senescence is an integrated response of plants to various internal
      (developmental) and external (environmental) signals. It is a highly regulated
      process leading eventually to the death of cells, single organs such as leaves,
      or even whole plants. In cereals, which are monocarpic plants, senescence
      represents the final stage of development. In order to study senescence in durum
      wheat (Triticum turgidum subsp. durum), a cDNA-AFLP analysis was performed. The
      transcription profiles of plants at different developmental stages (flowering and
      senescent) were compared. About 2000 cDNA fragments, ranging in size from 160 to
      1900 bp, were reproducibly detected. This allowed the identification of 57
      differentially expressed cDNAs corresponding to genes belonging to different
      functional categories related to cellular metabolism, transcription, maintenance
      of DNA structure, transport and signal transduction. This paper reports the
      identification of novel durum wheat candidate genes involved in the senescence
      process, and provides new information about the senescence programme of this
      important crop species.

PMID- 21197603
TI  - Relative outcome measures for bariatric surgery. Evidence against excess weight
      loss and excess body mass index loss from a series of laparoscopic Roux-en-Y
      gastric bypass patients.
AB  - BACKGROUND: Bariatric results expressed in the relative measure excess weight
      loss (%EWL) vary significantly by initial body mass index (BMI): the heavier the
      patient, the lower the %EWL. We examine if this variation is caused by using a
      wrong outcome measure and argue that no relative weight loss measure can express
      bariatric or metabolic goals unequivocally. METHODS: Nadir weight loss results
      after laparoscopic gastric bypass in 168 women with initial BMI >=35 to <60 kg/m2
      are calculated for %EWL and 61 different relative measures using the formula 100%
      * (initial BMI - nadir BMI) / (initial BMI-a), with a ranging from -30 to +30.
      Standard deviations are compared mutually and with those reported in the
      literature. For each relative measure, the significance of any variation by
      initial BMI is determined with the Mann-Whitney U test. RESULTS: Mean initial BMI
      was 44.9 +/- 6.7 (35.0-59.7) kg/m2. Mean nadir BMI was 28.8 +/- 5.8 (18.5-44.4)
      kg/m2. Mean nadir excess BMI loss (%EBL; a = 25) was 87.0 +/- 28.0 (19.4-155.1)%.
      Mean nadir (total) weight loss (%TWL; a = 0) was 35.9 +/- 8.5 (9.5-57.1)%. Mean
      nadir %EWL was 77.3 +/- 22.8 (17.7-135.2)%. The smallest variation coefficient
      was 23.7% at a ranging from -1 to +3, including %TWL (a = 0). This is lower than
      variation coefficients of %EWL results in our series and in the literature.
      Variation by initial BMI is significant using relative measures with a >=3,
      including %EBL and %EWL (both p < 0.0001) and not significant with a <3,
      including %TWL (p = 0.13). CONCLUSIONS: In contrast to their widespread use, %EBL
      and %EWL are not suited for comparing different patients or nonrandomized groups.
      They cause variation by initial BMI, which disappears using %TWL. In general,
      absolute terms should be preferred for bariatric outcome and goals. The power of
      bariatric procedures is best represented by their mean %TWL value.

PMID- 21197604
TI  - Food aversions in women during the 2 years after Roux-en-Y gastric bypass.
AB  - The anatomical and physiological changes of the gastrointestinal tract after Roux
      en-Y gastric bypass lead to changes in dietary patterns and their effects are
      still little known. Hence, the objective of this work was to characterize the
      prevalence, the associated factors and the list of food aversions with the effect
      of surgery on the body weight of women in the first two years after Roux-en-Y
      gastric bypass. A total of 141 women were studied. Their food aversions were
      assessed with a short food frequency questionnaire (FFQ-S) containing 26 items
      before and 6, 12 and 24 months after surgery. The FFQ-S was filled out during
      individual interviews and referenced in the medical records. The association
      between total aversion score and body weight variables and general
      characteristics of the group was analyzed. Variation of food aversions over time
      was assessed for 26 foods individually and grouped. Of all the studied variables,
      a weak but significant negative correlation (rs = -0.1944; p = 0.0208) was found
      between total aversion score and shorter postoperative period and a weak but
      significant positive correlation was found between total aversion score and
      percentage of weight regained (rs = -0.1759; p = 0.0369). Food aversions were
      more common in the first six months after surgery, especially to red meats, rice,
      chicken, eggs, pasta, milk and others. Food aversions in the early postoperative
      period are associated with weight variations in the first two years after surgery
      and subside significantly over time, probably because of a physiological and
      cognitive adaptation of the individual to the surgical procedure.

PMID- 21197605
TI  - Detecting residual cognitive function in disorders of consciousness.
AB  - Clinical audits have suggested up to 40% of patients with disorders of
      consciousness may be misdiagnosed, in part, due to the highly subjective process
      of determining, from a patient's behaviour, whether they retain awareness of self
      or environment. To address this problem, objective neuroimaging methods, such as
      positron emission tomography and functional magnetic resonance imaging have been
      explored. Using these techniques, paradigms, which do not require the patient to
      move or speak, can be used to determine a patient's level of residual cognitive
      function. Indeed, visual discrimination, speech comprehension and even the
      ability to respond to command have been demonstrated in some patients who are
      assumed to be vegetative on the basis of standard behavioural assessments.
      Functional neuroimaging is now increasingly considered to be a very useful and
      necessary addition to the clinical assessment process, where there is concern
      about the accuracy of the diagnosis and the possibility that residual cognitive
      function has remained undetected. In this essay, the latest neuroimaging findings
      are reviewed, the limitations and caveats pertaining to interpretation are
      outlined and the necessary developments, before neuroimaging becomes a standard
      component of the clinical assessment are discussed.

PMID- 21197606
TI  - Rationale for hypothalamus-deep brain stimulation in food intake disorders and
      obesity.
AB  - Appetite modulation in conjunction with enhancing metabolic rate with
      hypothalamic lesions has been widely documented in animal and even in humans. It
      appears these effects can be reproduced by DBS, and the titratability and
      reversibility of this procedure, in addition to well established safety profile,
      make DBS an appealing option for obesity treatment. Targeting the hypothalamus
      with DBS has already been shown to be feasible and potentially effective in
      managing patients with intractable chronic cluster headache [26]. The surgical
      risk however must be cautiously taken into account when targeting the
      hypothalamus, where some mortality cases have been reported when targeting the
      posterior part [34]. The development of new surgical approach will probably
      reduce this surgical risk. Moreover, the role of functional neurosurgery in
      obesity is not a new idea. In fact, LH was targeted in obese humans with
      electrocoagulation more than 30 years ago, resulting in significant yet transient
      appetite suppression and slight weight reduction [36]. All those elements have
      made possible the recent regain of interest in DBS for morbid obesity and open an
      exciting new area of research in neurosurgery and endocrinology.

PMID- 21197608
TI  - SEEG-guided RF-thermocoagulation of epileptic foci: a therapeutic alternative for
      drug-resistant non-operable partial epilepsies.
AB  - BACKGROUND: Previous literature includes numerous reports of acute stereotactic
      ablation for epilepsy. Most reports focus on amygdalotomies or
      amygdalohippocampotomies, some others focus on various extra-limbic targets.
      These stereotactic techniques proved to have a less favourable outcome than that
      of standard surgery, so that their rather disappointing benefit/risk ratio
      explains why they have been largely abandoned. However, depth electrode
      recordings may be required in some cases of epilepsy surgery to delineate the
      best region of cortical resection. We usually implant depth electrodes according
      to Talairach's stereo electroencephalography (SEEG) methodology. Using these
      chronically implanted depth electrodes, we are able to perform radiofrequency
      (RF)-thermolesions of the epileptic foci. This paper reports the technical data
      required to perform such multiple cortical thermolesions, as well as the results
      in terms of seizure outcome in a group of 41 patients. TECHNICAL DATA: Lesions
      are placed in the cortex areas showing either a low amplitude fast pattern or
      spike-wave discharges at the onset of the seizures. Interictal paroxysmal
      activities are not considered for planning thermocoagulation sites. All targets
      are first functionally evaluated using electrical stimulation. Only those showing
      no clinical response to stimulation are selected for thermolesion, including
      sites located inside or near primary functional area. Lesions are performed using
      120mA bipolar current (50 V), applied for 10-30 sec. Each thermocoagulation
      produces a 5-7mm diameter cortical lesion. A total of 2-31 lesions were performed
      in each of the 41 patients. Lesions are placed without anaesthesia. RESULTS: 20
      patients (48.7%) experienced a seizure frequency decrease of at least 50% that
      was more than 80% in eight of them. One patient was seizure free after RF
      thermocoagulation. In 21 patients, no significant reduction of the seizure
      frequency was observed. Amongst the characteristics of the disease (age and sex
      of the patient, lobar localization of the EZ) and the characteristics of the
      thermocoagulations (topography, lateralization, number, morphology of the lesions
      on MRI) no factor was significantly linked to the outcome. However, the best
      results were clearly observed in epilepsies symptomatic of a cortical development
      malformation (CDM), with 67% of responders in this group of 20 patients (p =
      0.052). Three transient post-procedure side-effects, consisting of paraesthetic
      sensations in the mouth (2 cases), and mild apraxia of the hand, were observed.
      CONCLUSION: SEEG-guided-RF-thermolesioning is a safe technique. Our results
      indicate that such lesions can lead to a significant reduction of seizure
      frequency. Our experience suggests that SEEG-guided RF thermocoagulation should
      be dedicated to drug-resistant epileptic patients for whom conventional resection
      surgery is risky or contra-indicated on the basis of invasive pre-surgical
      evaluation, particularly those suffering from epilepsy symptomatic of cortical
      development malformation.

PMID- 21197609
TI  - Child abuse - some aspects for neurosurgeons.
AB  - Neurosurgeons are mainly concerned with child abuse in cases of severe cranio
      cerebral trauma. Aim of the present paper is to highlight the clinical picture
      and symptoms in cases of child abuse and our multidisciplinary approach to reveal
      a solid diagnosis. The detection of child abuse requires a high index of
      suspicion, especially in cases of subtle injuries. Besides reporting to the
      appropriate agencies primary goals are to terminate suspected abuse and to
      prevent further harm to the child. All this requires a confirmed diagnosis.

PMID- 21197610
TI  - Prophylactic antibiotics and anticonvulsants in neurosurgery.
AB  - The prophylactic administration of antibiotics to prevent infection and the
      prophylactic administration of anticonvulsants to prevent first seizure episodes
      are common practice in neurosurgery. If prophylactic medication therapy is not
      indicated, the patient not only incurs the discomfort and the inconvenience
      resulting from drug treatment but is also unnecessarily exposed to adverse drug
      reactions, and incurs extra costs. The main situations in which prophylactic
      anticonvulsants and antibiotics are used are described and those situations we
      found controversial in the literature and lack further investigation are
      identified: anticonvulsants for preventing seizures in patients with chronic
      subdural hematomas, antiepileptic drugs for preventing seizures in those
      suffering from brain tumors, antibiotic prophylaxis for preventing meningitis in
      patients with basilar skull fractures, and antibiotic prophylaxis for the
      surgical introduction of intracranial ventricular shunts.In the following we
      present systematic reviews of the literature in accordance with the standard
      protocol of The Cochrane Collaboration to evaluate the effectiveness of the use
      of these prophylactic medications in the situations mentioned. Our goal was to
      efficiently integrate valid information and provide a basis for rational decision
      making.

PMID- 21197611
TI  - The dural sheath of the optic nerve: descriptive anatomy and surgical
      applications.
AB  - The aim of this work was to clarify the descriptive anatomy of the optic dural
      sheath using microanatomical dissections on cadavers. The orbit is the rostral
      part of the extradural neural axis compartment; the optic dural sheath forms the
      central portion of the orbit.In order to describe this specific anatomy, we
      carefully dissected 5 cadaveric heads (10 orbits) up to the meningeal structure
      of the orbit and its contents. 1 cadaveric head was reserved for electron
      microscopy to add to our knowledge of the collagen structure of the optic dural
      sheath.In this chapter, we describe the anatomy of the interperiostal-dural
      concept and the anatomy of the orbit. The optic dural sheath contains three
      portions: the intracranial, the intracanalicular and the intraorbital segment.
      Each one has specific anatomic relations which result in particular surgical
      considerations.

PMID- 21197607
TI  - Gustatory and reward brain circuits in the control of food intake.
AB  - Gustation is a multisensory process allowing for the selection of nutrients and
      the rejection of irritating and/or toxic compounds. Since obesity is a highly
      prevalent condition that is critically dependent on food intake and energy
      expenditure, a deeper understanding of gustatory processing is an important
      objective in biomedical research. Recent findings have provided evidence that
      central gustatory processes are distributed across several cortical and
      subcortical brain areas. Furthermore, these gustatory sensory circuits are
      closely related to the circuits that process reward. Here, we present an overview
      of the activation and connectivity between central gustatory and reward areas.
      Moreover, and given the limitations in number and effectiveness of treatments
      currently available for overweight patients, we discuss the possibility of
      modulating neuronal activity in these circuits as an alternative in the treatment
      of obesity.

PMID- 21197612
TI  - Surgical indications and techniques for failed coiled aneurysms.
AB  - For two decades, endovascular coiling has revolutionized the treatment of
      intracranial aneurysms. However, as with all techniques, it has limitations and
      endovascular radiologists and neurosurgeons are regularly confronted by what we
      call "failed" coiled aneurysms. Failed coiled aneurysms can occur in different
      situations: a) presence of a significant remnant at the end of an endovascular
      procedure; b) recanalization of an initially satisfactory occlusion; and c) coil
      extrusion deemed too thrombogenic or threatening the blood flow in the parent
      vessel. We and other teams around the world have developed strategies to manage
      these difficult cases. Here, we compare our own experience with other reports in
      the literature.

PMID- 21197615
TI  - Effects of oxazepam on affective perception, recognition, and event-related
      potentials.
AB  - BACKGROUND: Little is known about how rapid electrocortical responses (event
      related potentials; ERPs) to affective pictures are modulated by benzodiazepine
      agonists. The present study investigated effects of oxazepam (20 mg p.o.) on
      behavioral measures and ERPs associated with affective picture processing during
      perception and recognition memory retrieval. METHODS: Forty-three healthy young
      adults were given oxazepam or placebo treatment under a double-blind experimental
      procedure. Affective pictures (negatively arousing or neutral) elicited ERP
      responses and participants rated pictures for emotionality (during incidental
      encoding) and recognition. RESULTS: Oxazepam did not affect perceptual (P1, P2)
      or emotional (early posterior negativity and late parietal positivity) ERPs or
      ratings during perception. However, oxazepam impaired recognition performance and
      decreased positive mid-frontal ERP component at 420-450 ms for old vs. new
      pictures. The memory impairment was retained at the delayed memory test.
      CONCLUSIONS: Oxazepam does not selectively influence electrocortical or
      perceptual indexes of emotional perception or emotional memory. Rather, it blocks
      memory consolidation independent of valence category. These findings indicate
      that ERPs can be of use in assessing effects of benzodiazepines on memory-related
      processes.

PMID- 21197616
TI  - Social defeat stress in rats: escalation of cocaine and "speedball" binge self
      administration, but not heroin.
AB  - RATIONALE: Exposure to intermittent episodes of social defeat stress can increase
      drug seeking and leads to intense drug taking in rats. OBJECTIVES: This study
      investigated the consequences of repeated, intermittent social defeat stress on
      patterns of drug self-administration in rats with access to heroin, cocaine, or a
      heroin-cocaine combination ("speedball"). METHODS: Male Long-Evans rats were
      either handled (controls) or subjected to 25-min social defeat stress episodes on
      days 1, 4, 7, and 10 during confrontations with an aggressive resident. Ten days
      following the last defeat, rats were assessed for locomotor cross-sensitization
      in response to heroin or cocaine. Animals were then prepared with intrajugular
      catheters for drug self-administration. Separate groups of controls and defeated
      rats were examined for self-administration of heroin (experiment 1), a heroin
      cocaine combination (experiment 2), or cocaine (experiment 3). Drug self
      administration patterns were evaluated using fixed or progressive ratio schedules
      of reinforcement during limited access sessions or a 24-h unlimited access binge.
      RESULTS: Rats with a history of intermittent social defeat stress showed
      sensitized locomotor behavior when challenged with heroin or cocaine relative to
      controls. During the 24-h binge session, defeated rats escalated cocaine-taking
      behavior (ca. 110 mg/kg vs. 66 mg/kg in controls), persisted in self
      administering cocaine or the heroin-cocaine mixture for more hours, and showed a
      tendency for increased heroin-cocaine intake, but no effects on heroin taking.
      CONCLUSIONS: A history of social defeat stress seems to preferentially promote
      escalated intake of cocaine but not heroin, unless a heroin-cocaine combination
      is available.

PMID- 21197617
TI  - Downregulation of aquaporin-1 in alveolar microvessels in lungs adapted to
      chronic heart failure.
AB  - The threshold pressure for lung edema formation is increased in severe chronic
      heart failure (CHF) due to reduced microvascular permeability. The water channel
      aquaporin-1 (AQP1) is present in the pulmonary microvascular endothelium, and a
      number of studies suggest the importance of AQP1 as a molecular determinant of
      pulmonary microvascular water transport. The present study examined the abundance
      and localization of AQP1 in lungs from rats with CHF. We used two different
      models of CHF: ligation of the left anterior descending coronary artery (LAD
      ligation) and aorta-banding (AB). Sham-operated rats served as controls.
      Echocardiographic verification of left ventricular dysfunction, enhanced left
      ventricular end-diastolic pressure, and right ventricular hypertrophy confirmed
      the presence of CHF. Western blotting of whole-lung homogenates revealed
      significant downregulation of AQP1 in LAD-ligated rats (24 h: 58 +/- 5% of sham;
      3 weeks: 8 +/- 3% of sham; 9 weeks: 16 +/- 6% of sham) and after AB (30 weeks: 37
      +/- 5% of sham), whereas the protein levels of the specific endothelial cell
      marker PECAM-1 was increased 3 weeks after LAD ligation (229 +/- 20% of sham),
      but unchanged after 9 weeks and in the AB rats compared to controls.
      Immunohistochemical examination 3 weeks after LAD ligation showed intact labeling
      of PECAM-1 but an almost complete absence of AQP1 in the pulmonary alveolar
      microvessels in the CHF rats. These results suggest that downregulation of AQP1
      in the alveolar microvessels may act as a compensatory mechanism to protect
      against formation of excessive pulmonary edema in CHF.

PMID- 21197618
TI  - Model-based prediction of human hair color using DNA variants.
AB  - Predicting complex human phenotypes from genotypes is the central concept of
      widely advocated personalized medicine, but so far has rarely led to high
      accuracies limiting practical applications. One notable exception, although less
      relevant for medical but important for forensic purposes, is human eye color, for
      which it has been recently demonstrated that highly accurate prediction is
      feasible from a small number of DNA variants. Here, we demonstrate that human
      hair color is predictable from DNA variants with similarly high accuracies. We
      analyzed in Polish Europeans with single-observer hair color grading 45 single
      nucleotide polymorphisms (SNPs) from 12 genes previously associated with human
      hair color variation. We found that a model based on a subset of 13 single or
      compound genetic markers from 11 genes predicted red hair color with over 0.9,
      black hair color with almost 0.9, as well as blond, and brown hair color with
      over 0.8 prevalence-adjusted accuracy expressed by the area under the receiver
      characteristic operating curves (AUC). The identified genetic predictors also
      differentiate reasonably well between similar hair colors, such as between red
      and blond-red, as well as between blond and dark-blond, highlighting the value of
      the identified DNA variants for accurate hair color prediction.

PMID- 21197619
TI  - Invasive pulmonary aspergillosis in patients with HBV-related liver failure.
AB  - Invasive pulmonary aspergillosis (IPA) has been increasingly frequent in severe
      liver disease. We aim to investigate the clinical presentation, predisposing
      factors, and treatment of IPA in patients with liver failure caused by hepatitis
      B virus (HBV) infection. Medical records from 798 patients with HBV-related liver
      failure were reviewed. A total of 43 patients with probable IPA were selected as
      the case group, another 43 patients with bacterial infection and 43 patients
      without any infections were selected, for whose age, sex, date of admission, and
      the disease onset were matched with the case group. We evaluated the risk
      factors, clinical manifestations, treatment, and subsequent outcome of IPA in
      patients with HBV-related liver failure. Multivariate logistic regression models
      were used to demonstrate risk factors associated with IPA. Compared with patients
      with bacterial infection and those without any infection, patients with probable
      IPA used more antibiotics and steroids, and had poorer conditions and the highest
      mortality (P < 0.0001). Multiple antibiotics use and frequent invasive procedures
      were independent factors associated with the occurrence of IPA in patients with
      HBV-related liver failure. Patients with HBV-related liver failure are
      predisposed to IPA and may have a more severe condition and poorer prognosis.

PMID- 21197620
TI  - TRAIL shows potential cardioprotective activity.
AB  - Recent clinical trials carried out in patients with advanced cancer have shown
      that recombinant TRAIL administration is usually safe and well tolerated when
      used either alone or in association with chemotherapeutic drugs. Notably,
      anticancer chemotherapy can be associated to cardiomiopathy. We have here
      demonstrated that TRAIL (administrated as either recombinant soluble TRAIL or as
      AAV-TRAIL expression viral vector) reduced the development of cardiomyopathy in
      the ApoE(-/-) diabetic mouse model. These data suggest, for the first time, that
      therapeutically administration of TRAIL might have a cardioprotective effect.

PMID- 21197621
TI  - Chemopreventive effects of tolfenamic acid against esophageal tumorigenesis in
      rats.
AB  - The primary objective of this study is to identify small molecules that target
      critical transcription factors for potential application in the chemoprevention
      of esophageal cancer. Specificity proteins (Sp) play a critical role in the
      growth and metastasis of several malignancies including esophageal cancer.
      Researchers at the M. D. Anderson Cancer Center Orlando Cancer Research Institute
      have reported previously that tolfenamic acid (TA) inhibits cancer cell
      proliferation and tumor growth through the degradation of Sp1, Sp3, and Sp4. We
      evaluated the chemopreventive properties of TA against esophageal tumorigenesis
      in N-nitrosomethylbenzylamine (NMBA)-induced murine tumor model. Fischer-344 rats
      were treated with NMBA (0.5 mg/kg s.c. 3 times a week) for 5 weeks to initiate
      the tumor formation, and then treated with 50 mg/kg TA from week 6 through week
      25. Tumor incidence, tumor multiplicity (number of papilloma per rat), and tumor
      volume were evaluated after 25 weeks. All rats in the control group that received
      only NMBA developed lesions (100% incidence), while the TA-treated group showed
      significantly lower (33%) tumor incidence and tumor multiplicity. Furthermore,
      the tumor volume was significantly diminished in the TA-treated group when
      compared with the control group. Using small molecules such as TA to target key
      transcription factors associated with tumorigenesis for the prevention of
      esophageal malignancies is a new and promising strategy. Results of the current
      study provide evidence that TA, when given orally after tumor initiation, can
      significantly suppress tumorigenesis induced by carcinogenic nitrosamines in
      rats. These appealing results demonstrate that TA may potentially serve as an
      effective chemopreventive agent in patient populations vulnerable to esophageal
      cancer.

PMID- 21197622
TI  - Bevacizumab 5 or 7.5 mg/kg in metastatic colorectal cancer can be infused safely
      over 10 minutes.
AB  - BACKGROUND: Bevacizumab is a humanized monoclonal antibody that blocks vascular
      endothelial factor. It demonstrated an efficacy in many cancer types. The
      standard recommendation of administration is the 90-, 60-, and 30-min infusion
      sequence for all doses. We evaluated in this study the possibility of reducing
      infusion time to 10 min for bevacizumab given at 5 or 7.5 mg/kg in metastatic
      colorectal cancer (MCRC). PATIENTS AND METHODS: All patients who received
      bevacizumab for MCRC were analyzed. Patients were divided into two groups: Group
      A (bevacizumab was given in the 90-, 60-, and 30-min infusion sequence) and group
      B (bevacizumab was given over 10 min). Patients' medical records were used to
      identify any hypersensitivity reactions (HSR) possibly related to bevacizumab.
      RESULTS: There were 38 patients in group A and 43 in group B. In group A, 459
      doses of bevacizumab were given (286 doses at 5 mg/kg and 173 doses at 7.5
      mg/kg). No HSR occurred in this group. In group B, 527 doses of bevacizumab were
      given (335 doses at 5 mg/kg and 192 doses at 7.5 mg/kg). Only two events of HSR
      grade 2 were reported in the 7.5 mg/kg infusions. Both of them were easily
      resolved with symptomatic treatment. CONCLUSIONS: Bevacizumab 5 or 7.5 mg/kg in
      MCRC can be infused safely over 10 min.

PMID- 21197623
TI  - Hyperbilirubinemia and intermittent lower urinary tract dysfunction.
AB  - OBJECTIVE: To examine the effect of hyperbilirubinemia on lower urinary tract
      function. METHODS: The study was conducted on 29 patients with suspected
      Gilbert's syndrome (GS), and who were subjected to fasting test for diagnostic
      purpose. The uroflowmetric test was performed after 24 h of fasting and after 24
      h of hypercaloric intake. RESULTS: After a 24 h fasting period, when bilirubin in
      the serum was at its highest concentration, 31% of patients had abnormal
      uroflowmetric patterns. Patients with abnormal uroflowmetric patterns had higher
      conjugated bilirubin after 24 h fasting period than patients with normal pattern
      (p = 0.012). After a 24 h of hypercaloric intake, all 29 patients had a normal
      (bell-shaped) uroflowmetric pattern. CONCLUSIONS: The results imply that
      hyperbilirubinemia might be a predisposing factor for intermittent lower urinary
      tract dysfunction in children.

PMID- 21197644
TI  - Atypical teratoid/rhabdoid tumor: analysis of cytomorphologic features in CSF,
      focused on the differential diagnosis from mimickers.
AB  - Atypical teratoid and rhabdoid tumor (AT/RT) is a rare tumor with fatal clinical
      consequences, usually affecting young children. A significant portion of patients
      present with dissemination to cerebrobspinal fluid (CSF). However, a limited
      number of studies are available regarding the cytomorphologic findings of AT/RT
      in CSF. We collected eight cases of CSF cytology of AT/RT and describe the
      cytomorphologic features of AT/RT in CSF. Typical rhabdoid cells are found in
      most cases and they are characterized by eccentric nuclei, abundant cytoplasm,
      and clustering of the tumor cells. The presence of these cells in CSF indicates
      disseminated diseases and aggressive therapeutic consideration for patient
      management is required.

PMID- 21197624
TI  - Mechanism of chronic migraine.
AB  - Chronic migraine typically evolves from episodic migraine over months to years in
      susceptible individuals. Headaches increase in frequency over time, becoming less
      intense but more disabling and less responsive to treatment. Results of
      electrophysiologic and functional imaging studies indicate that chronic migraine
      is associated with abnormalities in the brainstem that may be progressive.
      Additionally, chronic migraine is associated with a greater degree of impairment
      in cortical processing of sensory stimuli than is episodic migraine, perhaps due
      to a more pervasive or persistent cortical hyperexcitability. These findings fit
      with the model of migraine as a spectrum disorder, in which the clinical and
      pathophysiological features of migraine may progress over time. This progression
      is postulated to result from changes in nociceptive thresholds and ensuing
      central sensitization caused by recurrent migraine in susceptible individuals,
      for whom a variety of risk factors have been described. This may lead to changes
      in baseline neurologic function between episodes of headache, evident not only in
      electrophysiologic and functional imaging studies, but also as an increase in
      depression, anxiety, nonhead pain, fatigue, gastrointestinal disorders, and other
      somatic complaints that may occur after years of episodic migraine. From the
      current research and migraine models, a conceptualization of chronic migraine, in
      which relatively permanent and pervasive central changes that warrant novel and
      tolerable treatments have occurred, is emerging. This model also implies that
      prevention of chronic migraine is an important goal in the management of episodic
      migraine, particularly in individuals who exhibit risk factors for chronic
      transformation.

PMID- 21197651
TI  - Computational systems biology of aging.
AB  - Computational systems biology is expected to make major contributions to unravel
      the complex molecular mechanisms underlying the progression of aging in cells,
      tissues, and organisms. The development of computational approaches is, however,
      challenged by a wide spectrum of aging mechanisms participating on different
      levels of biological organization. The tight connectivity between the molecular
      constituents, functions, and cell states requires frameworks and strategies that
      extend beyond current practice to model, simulate, and predict the progression of
      aging and the emerging aging phenotypes. We provide a general overview of the
      specific computational tasks and opportunities in aging research, and discuss
      some illustrative systems level concepts in more detail. One example provided
      here is the assembly of a conceptual whole cell model that considers the temporal
      dynamics of the aging process grounded on molecular mechanisms. Another
      application is the assembly of interactomes, such as protein networks that allow
      us to analyze changes in network topology and interaction of proteins that have
      been implicated in aging with other cellular constituents and processes. We
      introduce the necessary key steps to build these applications and discuss their
      merits and future extensions for aging research. WIREs Syst Biol Med 2011 3 414
      428 DOI: 10.1002/wsbm.126

PMID- 21197652
TI  - Where gene discovery turns into systems biology: genome-scale RNAi screens in
      Drosophila.
AB  - Systems biology aims to describe the complex interplays between cellular building
      blocks which, in their concurrence, give rise to the emergent properties observed
      in cellular behaviors and responses. This approach tries to determine the
      molecular players and the architectural principles of their interactions within
      the genetic networks that control certain biological processes. Large-scale loss
      of-function screens, applicable in various different model systems, have begun to
      systematically interrogate entire genomes to identify the genes that contribute
      to a certain cellular response. In particular, RNA interference (RNAi)-based high
      throughput screens have been instrumental in determining the composition of
      regulatory systems and paired with integrative data analyses have begun to
      delineate the genetic networks that control cell biological and developmental
      processes. Through the creation of tools for both, in vitro and in vivo genome
      wide RNAi screens, Drosophila melanogaster has emerged as one of the key model
      organisms in systems biology research and over the last years has massively
      contributed to and hence shaped this discipline. WIREs Syst Biol Med 2011 3 471
      478 DOI: 10.1002/wsbm.127

PMID- 21197653
TI  - Genome-wide approaches in the study of microRNA biology.
AB  - MicroRNAs (miRNAs), a class of ~21-23 nucleotide long non-coding RNAs (ncRNAs),
      have critical roles in diverse biological processes that encompass development,
      proliferation, apoptosis, stress response, and fat metabolism. miRNAs recognize
      their target mRNA transcripts by partial sequence complementarity and
      collectively have been estimated to regulate the majority of human genes.
      Consequently, misregulation of miRNAs or disruption of their target sites in
      genes has been implicated in a variety of human diseases ranging from cancer
      metastasis to neurological disorders. With the development and availability of
      genomic technologies and computational approaches, the field of miRNA biology has
      advanced tremendously over the last decade. Here we review the genome-wide
      approaches that have allowed for the discovery of new miRNAs, the
      characterization of their targets, and a systems-level view of their impact.

PMID- 21197654
TI  - Influenza A virus infection kinetics: quantitative data and models.
AB  - Influenza A virus is an important respiratory pathogen that poses a considerable
      threat to public health each year during seasonal epidemics and even more so when
      a pandemic strain emerges. Understanding the mechanisms involved in controlling
      an influenza infection within a host is important and could result in new and
      effective treatment strategies. Kinetic models of influenza viral growth and
      decay can summarize data and evaluate the biological parameters governing
      interactions between the virus and the host. Here we discuss recent viral kinetic
      models for influenza. We show how these models have been used to provide insight
      into influenza pathogenesis and treatment, and we highlight the challenges of
      viral kinetic analysis, including accurate model formulation, estimation of
      important parameters, and the collection of detailed data sets that measure
      multiple variables simultaneously. WIREs Syst Biol Med 2011 3 429-445 DOI:
      10.1002/wsbm.129

PMID- 21197655
TI  - Cardiac function and disease: emerging role of small ubiquitin-related modifier.
AB  - Small ubiquitin-related modifiers, or SUMOs, have emerged as versatile regulators
      of many biological functions that do so by covalent attachment to a variety of
      substrates via enzymatic reactions. SUMO conjugation has also been shown to be
      involved in a number of human pathogenic processes. More recent advances in the
      SUMO field have indicated a potential role for SUMO conjugation pathway in
      cardiogenesis. This advanced review will describe the basic features of the SUMO
      conjugation pathway and will summarize the most recent studies implicating the
      influence of the sumoylation pathway in cardiac function under both physiological
      and pathological conditions. WIREs Syst Biol Med 2011 3 446-457 DOI:
      10.1002/wsbm.130

PMID- 21197656
TI  - A multifaceted approach to modeling the immune response in tuberculosis.
AB  - Tuberculosis (TB) is a deadly infectious disease caused by Mycobacterium
      tuberculosis (Mtb). No available vaccine is reliable and, although treatment
      exists, approximately 2 million people still die each year. The hallmark of TB
      infection is the granuloma, a self-organizing structure of immune cells forming
      in the lung and lymph nodes in response to bacterial invasion. Protective immune
      mechanisms play a role in granuloma formation and maintenance; these act over
      different time/length scales (e.g., molecular, cellular, and tissue scales). The
      significance of specific immune factors in determining disease outcome is still
      poorly understood, despite incredible efforts to establish several animal systems
      to track infection progression and granuloma formation. Mathematical and
      computational modeling approaches have recently been applied to address open
      questions regarding host-pathogen interaction dynamics, including the immune
      response to Mtb infection and TB granuloma formation. This provides a unique
      opportunity to identify factors that are crucial to a successful outcome of
      infection in humans. These modeling tools not only offer an additional avenue for
      exploring immune dynamics at multiple biological scales but also complement and
      extend knowledge gained via experimental tools. We review recent modeling efforts
      in capturing the immune response to Mtb, emphasizing the importance of a
      multiorgan and multiscale approach that has tuneable resolution. Together with
      experimentation, systems biology has begun to unravel key factors driving
      granuloma formation and protective immune response in TB. WIREs Syst Biol Med
      2011 3 479-489 DOI: 10.1002/wsbm.131

PMID- 21197657
TI  - Layers of epistasis: genome-wide regulatory networks and network approaches to
      genome-wide association studies.
AB  - The conceptual foundation of the genome-wide association study (GWAS) has
      advanced unchecked since its conception. A revision might seem premature as the
      potential of GWAS has not been fully realized. Multiple technical and practical
      limitations need to be overcome before GWAS can be fairly criticized. But with
      the completion of hundreds of studies and a deeper understanding of the genetic
      architecture of disease, warnings are being raised. The results compiled to date
      indicate that risk-associated variants lie predominantly in noncoding regions of
      the genome. Additionally, alternative methodologies are uncovering large and
      heterogeneous sets of rare variants underlying disease. The fear is that, even in
      its fulfillment, the current GWAS paradigm might be incapable of dissecting all
      kinds of phenotypes. In the following text, we review several initiatives that
      aim to overcome these limitations. The overarching theme of these studies is the
      inclusion of biological knowledge to both the analysis and interpretation of
      genotyping data. GWAS is uninformed of biology by design and although there is
      some virtue in its simplicity, it is also its most conspicuous deficiency. We
      propose a framework in which to integrate these novel approaches, both empirical
      and theoretical, in the form of a genome-wide regulatory network (GWRN). By
      processing experimental data into networks, emerging data types based on
      chromatin immunoprecipitation are made computationally tractable. This will give
      GWAS re-analysis efforts the most current and relevant substrates, and root them
      firmly on our knowledge of human disease.

PMID- 21197659
TI  - Network biology: a direct approach to study biological function.
AB  - In this paper we discuss the dualism of gene networks and their role in systems
      biology. We argue that gene networks (1) can serve as a conceptual framework,
      forming a fundamental level of a phenomenological description, and (2) are a
      means to represent and analyze data. The latter point does not only allow a
      systems analysis but is even amenable for a direct approach to study biological
      function. Here we focus on the clarity of our main arguments and conceptual
      meaning of gene networks, rather than the causal inference of gene networks from
      data. WIREs Syst Biol Med 2011 3 379-391 DOI: 10.1002/wsbm.134 For further
      resources related to this article, please visit the WIREs website.

PMID- 21197658
TI  - Ischemic kidney injury and mechanisms of tissue repair.
AB  - Acute kidney injury (AKI) may result from ischemia or by the use of nephrotoxic
      agents. The incidence of AKI is variable, depends on comorbidities, and ranges
      from 5 to 35% in all hospitalized patients. The mechanisms of kidney injury exist
      within a large network of signaling pathways driven by interplay of inflammatory
      cytokines/chemokines, reactive oxygen species (ROS), and apoptotic factors. The
      effects and progression of injury overlap extensively with the remarkable ability
      of the kidney to repair itself both by intrinsic and extrinsic mechanisms that
      involve specific cell receptors/ligands as well as possible paracrine influences.
      The fact that kidney injury is usually part of a generalized comorbid condition
      makes it all the more challenging in terms of assessment of severity. In this
      review, we attempt to analyze the mechanisms of ischemic injury and repair in
      acute and chronic kidney disease from the perspectives of both preclinical and
      human studies.

PMID- 21197665
TI  - Functional genomics of the brain: uncovering networks in the CNS using a systems
      approach.
AB  - The central nervous system (CNS) is undoubtedly the most complex human organ
      system in terms of its diverse functions, cellular composition, and connections.
      Attempts to capture this diversity experimentally were the foundation on which
      the field of neurobiology was built. Until now though, techniques were either
      painstakingly slow or insufficient in capturing this heterogeneity. In addition,
      the combination of multiple layers of information needed for a complete picture
      of neuronal diversity from the epigenome to the proteome requires an even more
      complex compilation of data. In this era of high-throughput genomics though, the
      ability to isolate and profile neurons and brain tissue has increased
      tremendously and now requires less effort. Both microarrays and next-generation
      sequencing have identified neuronal transcriptomes and signaling networks
      involved in normal brain development, as well as in disease. However, the
      expertise needed to organize and prioritize the resultant data remains
      substantial. A combination of supervised organization and unsupervised analyses
      are needed to fully appreciate the underlying structure in these datasets. When
      utilized effectively, these analyses have yielded striking insights into a number
      of fundamental questions in neuroscience on topics ranging from the evolution of
      the human brain to neuropsychiatric and neurodegenerative disorders. Future
      studies will incorporate these analyses with behavioral and physiological data
      from patients to more efficiently move toward personalized therapeutics.

PMID- 21197660
TI  - Adaptation of cells to new environments.
AB  - The evolutionary success of an organism is a testament to its inherent capacity
      to keep pace with environmental conditions that change over short and long
      periods. Mechanisms underlying adaptive processes are being investigated with
      renewed interest and excitement. This revival is partly fueled by powerful
      technologies that can probe molecular phenomena at a systems scale. Such studies
      provide spectacular insight into the mechanisms of adaptation, including rewiring
      of regulatory networks via natural selection of horizontal gene transfers, gene
      duplication, deletion, readjustment of kinetic parameters, and myriad other
      genetic reorganizational events. Here, we discuss advances in prokaryotic systems
      biology from the perspective of evolutionary principles that have shaped
      regulatory networks for dynamic adaptation to environmental change.

PMID- 21197667
TI  - Whole transcriptome analysis: what are we still missing?
AB  - New technologies such as tag-based sequencing and tiling arrays have provided
      unique insights into the transcriptional output of cells. Many new RNA classes
      have been uncovered in the past decade, despite limitations in current
      technologies. Even as the repertoire of known functional elements of the
      transcriptome increases and contemporary technologies become mainstream,
      inadequacies in conventional protocols for library preparation, sequencing and
      mapping continue to hamper revelation of the entire transcriptome of cells. In
      this article, we review current protocols and outline their deficiencies. We also
      provide our view on what we may be overlooking in the transcriptome, despite
      exhaustive investigations, and indicate future areas of technological development
      and research.

PMID- 21197679
TI  - Androgen-dependent measurements of female genitalia in women with complete
      androgen insensitivity syndrome.
AB  - Measurements of clitoral length and clitoral to urethral distance were made and
      analysed for a relationship in a group of 19 women with complete androgen
      insensitivity syndrome (CAIS)attending a specialist clinic for adult women with
      disorders of sexual development. These were compared with a control group of 50
      women attending hospital for a gynaecological procedure.There was a positive
      correlation between clitoral length and clitoral to urethral distance for women
      with CAIS. In contrast, a negative correlation was seen between clitoral length
      and clitoral to urethral distance for women in the control group. Women with CAIS
      had a reduced mean clitoral length compared with controls(P = 0.001), but no
      difference was observed for the clitoral to urethral distance between the two
      groups (P = 0.116).

PMID- 21197666
TI  - Human cardiomyogenesis and the need for systems biology analysis.
AB  - Cardiovascular disease remains the leading cause of death in the Western world
      and myocardial infarction is one of the primary facets of this disease. The
      limited natural self-renewal of cardiac muscle following injury and restricted
      supply of heart transplants has encouraged researchers to investigate other means
      to stimulate regeneration of damaged myocardium. The plasticity of stem cells
      toward multiple lineages offers the potential to repair the heart following
      injury. Embryonic stem cells have been extensively studied for their ability to
      differentiate into early cardiomyocytes, however, the pathway has only been
      partially defined and inadequate efficiency limits their clinical applicability.
      Some studies have shown cardiomyogenesis from adult mesenchymal stem cells, from
      both bone marrow and adipose tissue, but their differentiation pathway remains
      poorly detailed and these results remain controversial. Despite promising results
      using stem cells in animal models of cardiac injury, the driving mechanisms
      behind their differentiation down a cardiomyogenic pathway have yet to be
      determined. Currently, there is a paucity of information regarding
      cardiomyogenesis on the systemic level. Stem cell differentiation results from
      multiple signaling parameters operating in a tightly regulated spatiotemporal
      pattern. Investigating this phenomenon from a systems biology perspective could
      unveil the abstruse mechanisms controlling cardiomyogenesis that would otherwise
      require extensive in vitro testing.

PMID- 21197680
TI  - Reasons for the increasing incidence of macrosomia in Harbin, China.
AB  - A population-based retrospective study was conducted in Harbin,China. The medical
      records of 13 711 singleton infants born between 2001 and 2005 in 16 hospitals
      were reviewed. The incidence of macrosomia (birthweight >=4000 g) was found to
      have increased from 8.31% in 2001 to 10.50% in 2005. Over this period, the
      ponderal index decreased and birth length increased in infants with macrosomia.
      In a multivariate analysis, risk factors for delivery of a newborn with
      macrosomia were found to be high prepartal body mass index (BMI), maternal height
      >=165 cm, male gender of the newborn, gestational age of 40-41.9 weeks, maternal
      age >=30 years and a maternal diagnosis of hypertension. The increase in the
      incidence of macrosomia in Harbin was attributable to increases in maternal
      prepartal BMI, height and age in the population.

PMID- 21197681
TI  - Antenatal magnesium sulphate may prevent cerebral palsy in preterm infants--but
      are we convinced? Evaluation of an apparently conclusive meta-analysis with trial
      sequential analysis.

PMID- 21197682
TI  - Maternal screening and postpartum vaccination for measles infection in Japan: a
      cohort study.
AB  - We investigated the prevalence of measles-sensitive pregnant women and the
      clinical usefulness of measles vaccination in postpartum women. Measles antibody
      levels were measured in 751 pregnant women. Forty-four women were vaccinated
      postpartum, and screened for antibody levels and adverse effects 1 month after
      vaccination. The prevalence of measles-sensitive pregnant women was 10-20%, with
      the highest prevalence in those under 24 years of age. Almost all (97.7%)
      vaccinated women acquired immunity, and did not show any adverse effects. Serum
      measles antibody levels should be determined in all pregnant women as a screening
      tool,and sensitive women should be vaccinated immediately after delivery.

PMID- 21197684
TI  - I'm 84 and I'm wondering if there is an upper age limit for stents to be placed
      in my coronary arteries or if I can take medication instead of having the stents
      put in?

PMID- 21197683
TI  - What you need to know about CCBs.  Calcium channel blockers reduce the effect of
      calcium on the heart and arteries.

PMID- 21197685
TI  - I've read a number of articles in recent years about nitric oxide (NO) and how it
      can help improve circulation.  Can you explain how that works and are there
      supplements available or things I can do to improve NO levels in my body?

PMID- 21197686
TI  - I have a history of heart disease in my family: my father and grandfather both
      had heart problems, and my sister has high blood pressure. Aside from slightly
      elevated cholesterol, I have no signs of heart trouble. I've never smoked and I'm
      at a healthy weight. How likely is it that my family history will "catch up with
      me"?

PMID- 21197687
TI  - I had a tissue aortic valve transplant two years ago, and today I feel great. The
      fatigue is gone and I exercise every day. But when I had an echocardiogram, I had
      an ejection fraction of 55 percent, which was better than my pre-transplant
      ejection fraction of 35 percent, though still at the low end of 'normal'. Why is
      the ejection fraction still fairly low, and can it ever improve?

PMID- 21197688
TI  - [Heart failure. Heart rate control prevents clinical complications].

PMID- 21197689
TI  - [Pediatric emergencies. Are you equipped?].

PMID- 21197691
TI  - [Research on biological, psychosocial and biomechanical aspects of health
      workers. Proceedings of the SIMLII National Congress, 3-5 March 2010, Pavia,
      Italy].

PMID- 21197690
TI  - [Special emergencies in children. The lege artis approach].

PMID- 21197692
TI  - [Proceedings of the 73rd National SIMLII Congress, 1-4 December 2010, Rome,
      Italy].

PMID- 21197693
TI  - Commentary on Aselage MB (2010) Measuring mealtime difficulties: eating, feeding
      and meal behaviours in older adults with dementia. Journal of Clinical Nursing
      19, 621-631.

PMID- 21197694
TI  - Commentary on Chan MF (2010) Factors affecting nursing staff in practicing
      spiritual care. Journal of Clinical Nursing 19, 2128-2136.

PMID- 21197695
TI  - Vitamin D: an ancient hormone.
AB  - Vitamin D has been produced by plants and animals almost from the time life
      began. The ability to transport and metabolize vitamin D to more active forms
      evolved as the structures of plants and animals became more complex, and the
      cells within these organisms took on more specialized functions. In higher-order
      animals, the vitamin D receptor (VDR) is found in nearly every cell, and the
      ability of the cell to produce the active hormone, 1,25(OH)2D, is also widely
      distributed. Furthermore, the physiological functions with which vitamin D
      signalling is now associated are as diverse as the tissues in which the VDR is
      located. Why is this, and is there a common theme? This viewpoint article argues
      that there is. All cells maintain a fairly constant and submicromolar
      concentration of free calcium. Calcium is an important regulator of many
      processes within the cell. The ebb and flow of calcium within cells is controlled
      by calcium pumps, antiporters and channels. Animals with calcified exo- or
      endoskeletons have an additional need for calcium, a need that changes during the
      life cycle of the organism. In this article, I make the case that vitamin D
      signalling evolved to enable the organism to effectively regulate calcium flux,
      storage and signalling and that such regulation is critical for the evolutionary
      process.

PMID- 21197696
TI  - Craniofacial biomechanics: in vivo to in silico.

PMID- 21197697
TI  - Life history collages: effects on nursing home staff caring for residents with
      dementia.
AB  - This study evaluated the effects of person-centered life history collages on
      nursing staff knowledge about individual residents living with dementia and staff
      perceptions of individualized care practices. Thirty-six nursing staff
      participants (18 experimental and 18 control) who cared for 5 residents with
      dementia in two nursing homes were recruited. Intervention staff members were
      exposed to life history collages for 4 weeks. Pretest and posttest data were
      analyzed using multivariate analysis of covariance and analysis of covariance.
      While intervention group members' knowledge of residents' family, jobs/careers,
      and likes/dislikes/interests improved significantly at posttest, F(3, 26) = 6.80,
      p < 0.01, and at 3 weeks postintervention, F(3, 23) = 9.85, p < 0.001,
      perceptions of individualized care/person-centered care practices did not.
      Potential reasons for this lack of improvement are identified and discussed.
      Directions for future research are also provided.

PMID- 21197698
TI  - Morphological and electron microscopic characteristics of grey platelet syndrome.

PMID- 21197699
TI  - Central palatal perforation in nasal natural killer cell lymphoma.

PMID- 21197700
TI  - Obesity: Benefits of intensive lifestyle modification programs in the spotlight.

PMID- 21197701
TI  - Cancer: RANKL inhibition-a new weapon against breast cancer?

PMID- 21197702
TI  - Diabetes: Treatment with losartan increases risk of adverse renal outcomes.

PMID- 21197703
TI  - Reproductive endocrinology: Diabetes, puberty and pcoS risk.

PMID- 21197705
TI  - Cancer: Predictors of metabolic outcome after surgery for adrenal incidentaloma.

PMID- 21197704
TI  - Soluble receptor for advanced glycation end products  is associated with in-stent
      restenosis in patients with  type 2 diabetes with drug-eluting coronary stents.
AB  - BACKGROUND: The levels of soluble receptor for advanced glycation end products
      (sRAGE) may reflect the activity of the advanced glycation end products-RAGE
      axis, which has been proposed as a potential mechanism of vascular inflammation
      in patients with type 2 diabetes (T2D). However, the role of sRAGE in in-stent
      restenosis (ISR) is not yet known in patients with T2D with drug-eluting stent
      (DES) implantation. METHODS AND RESULTS: We enrolled 35 patients with T2D with
      ISR (T2D-ISR) and 35 patients with age-matched T2D without ISR (T2D-control) at
      the time of follow-up coronary angiography after DES implantation. Plasma levels
      of glycosylated hemoglobin (HbA(1c)), C-reactive protein (CRP), insulin-like
      growth factor-1 (IGF-1), and sRAGE were measured in blood samples obtained at the
      time of the index procedure. Baseline characteristics showed no difference
      between the groups. Plasma levels of sRAGE were significantly higher in the T2D
      ISR group than in the T2D-control group (7.29 +/- 2.91 vs. 5.36 +/- 2.20 ng/ml,
      P= 0.003), but levels of HbA(1c) (7.65 +/- 1.59% vs. 7.60 +/- 1.65%, P = 0.89),
      CRP (8.15 +/- 13.82 vs. 5.59 +/- 7.68 mg/l, P = 0.34), and IGF-1 (0.93 +/- 0.37
      vs. 0.99 +/- 0.30 ng/ml, P = 0.42) did not differ significantly between the two
      study groups. In multivariate logistic regression analysis, elevated plasma level
      of sRAGE (above the median) was a significant predictor of ISR [odds ratio (OR):
      4.33, 95% confidence interval (CI): 1.38-13.59, P = 0.01], followed by mean stent
      diameter less than 3.0mm (OR: 3.35, CI: 0.98-11.46, P = 0.05). CONCLUSION: Plasma
      level of sRAGE may be positively associated with ISR and RAGE-dependent
      inflammatory responses may contribute more to ISR development than IGF-1
      dependent proliferative responses in patients with T2D with DES implantation.

PMID- 21197706
TI  - Risk factors: Estrogen and kidney stones.

PMID- 21197707
TI  - Bone: Teriparatide improves outcomes of periodontal surgery.

PMID- 21197709
TI  - Toll-like receptor 4 contributes to small intestine allograft rejection.
AB  - BACKGROUND: Although outcomes for small intestine transplantation (SIT) have
      improved in recent years, allograft rejection rates remain among the highest of
      solid organ grafts. The high load of commensal bacteria in the small intestine
      may contribute through activation of the toll-like receptor (TLR) pathway. In
      this study, we examine the participation of TLR4 in acute allograft rejection in
      an orthotopic mouse model of SIT. METHODS: Wild-type C57Bl/6 (H-2b) or TLR49(-/-)
      (H-2b) mice were transplanted with syngeneic (C57Bl/6), allogeneic (BALB/c; H
      2d), or F1 (BALB/cxC57Bl/6; H-2d/b) vascularized, orthotopic small intestine
      grafts. Graft recipients were killed on days 2 to 6 posttransplant. Serum
      cytokines were measured by Luminex, and tissue was obtained for histology and
      quantitative real-time polymerase chain reaction. RESULTS: BALB/c grafts
      transplanted into C57Bl/6 recipients exhibited mixed inflammatory infiltrates,
      destruction of the mucosa, and significant apoptosis. TLR2 and TLR4 transcripts
      were modestly increased in syngeneic grafts on days 2 and 6 compared with native
      bowel, whereas TLR2 and TLR4 were significantly increased on days 2 and 6 in
      allogeneic grafts. Although fully mismatched and F1 grafts were rejected by
      C57Bl/6 recipients (mean survival time=8.2 and 9.3 days, respectively), graft
      survival was significantly prolonged in TLR4(-/-) recipients (mean survival
      time=10.6 and 14.3 days, respectively). Proinflammatory cytokines were markedly
      reduced in TLR4(-/-) graft recipients. CONCLUSIONS: Small intestine graft
      survival is prolonged in the absence of TLR4, suggesting that gut flora
      associated with the graft may augment alloimmune responses through TLR4. Thus,
      the TLR pathway may be a novel therapeutic target for improving SIT allograft
      survival.

PMID- 21197710
TI  - Molecular basis of applied biological therapeutics.

PMID- 21197711
TI  - Xenograft of microencapsulated sertoli cells reverses T1DM in NOD mice by
      inducing neogenesis of beta-cells.
AB  - BACKGROUND: Sertoli cells (SCs) provide an immunoprotective environment to
      pancreatic islet grafts for treatment of insulin-dependent diabetes. Aim of this
      work was to verify whether intraperitoneal graft of SCs, enveloped in barium
      alginate-based microcapsules, would reverse overt spontaneous diabetes in
      nonobese diabetic (NOD) mice by eliciting generation of newly formed functional
      islets beta-cells. METHODS: Microcapsules were prepared, according to our method,
      by a mono air-jet device system and thereafter examined as far as (a) SC
      morphology by light microscopy; (b) SC viability by fluorescence microscopy; (c)
      SC in vitro function; and (d) SC in vivo function, as quoted by diabetes reversal
      in the NOD mice, were concerned. RESULTS: SCs containing microcapsules exhibited
      excellent morphology, viability, and function, and when grafted into the NOD's,
      they induced stable reversion of the disease in 81% of the cases. The treated
      mice showed dramatic increase in regulatory T lymphocytes (Treg) when compared
      with control diabetic NOD's treated with empty capsules only. Histologic
      examination of pancreata retrieved from the SC-transplanted animals showed total
      disappearance of insulitis, with appearance of new islets, as shown by
      immunocytochemistry; restored ability of the islets to produce insulin, glucagon,
      and somatostatin; and finally, increased expression of key transcriptional
      factors such as neurogenin 3. CONCLUSIONS: SCs, enveloped in barium alginate
      based microcapsules, showed no long-term loss of their functional and
      morphological properties in vitro or in vivo. Xenograft of microencapsulated-SC
      induced reversal of spontaneous diabetes in the majority of the treated NOD mice,
      based on SC-related powerful immunomodulatory and pro-beta-cell regeneration
      properties.

PMID- 21197712
TI  - Attenuation of cross-talk between the complement and coagulation cascades by C5a
      blockade improves early outcomes after intraportal islet transplantation.
AB  - BACKGROUND: Complement 5a factor (C5a) elicits a broad range of proinflammatory
      effects, including chemotaxis of inflammatory cells and cytokine release. C5a is
      also linked to the coagulant activity in autoimmune diseases. Therefore, C5a most
      likely plays a crucial role in the instant blood-mediated inflammatory reaction.
      METHODS: Intraportal transplantation of 2.5 islet equivalents/g of syngeneic rat
      islet grafts was performed in two groups of streptozotocin-induced diabetic rats:
      controls and C5a inhibitory peptide (C5aIP)-treated group. RESULTS: The thrombin
      antithrombin complex was significantly suppressed in the C5aIP group (P=0.003),
      and both the curative rate and the glucose tolerance were significantly improved
      in the C5aIP group (P<0.05 and P<0.005, respectively). Expression of tissue
      factor on granulocytes in recipient livers was up-regulated 1 h after islet
      infusion (P<0.0001), which was significantly suppressed by C5aIP (P<0.005).
      However, C5aIP was unable to regulate tissue factor expression on isolated
      islets. Furthermore, no differences were detected between the groups, regarding
      infiltration of CD11b-positive cells and deposition of C5b-9 on the islet grafts.
      CONCLUSIONS: These data suggest that C5aIP attenuates cross-talk between the
      complement and coagulation cascades through suppressing up-regulation of tissue
      factor expression on leukocytes in recipient livers but not on islet grafts, a
      process leading to improvement in islet engraftment. Therefore, C5aIP in
      combination with conventional anticoagulants could be a strong candidate strategy
      to control the instant blood-mediated inflammatory reaction induced in clinical
      islet transplantation.

PMID- 21197713
TI  - Extended valganciclovir prophylaxis in D+/R- kidney transplant recipients is
      associated with long-term reduction in cytomegalovirus disease: two-year results
      of the IMPACT study.
AB  - BACKGROUND: Whether the early reduction in cytomegalovirus (CMV) disease seen at
      1 year with prolongation of antiviral prophylaxis (up to 200 days) persists in
      the long term is unknown. METHODS: This international, randomized, prospective,
      double-blind study, compared 318 CMV D+/R- kidney transplant recipients receiving
      valganciclovir (900 mg) once daily for up to 200 days vs. 100 days. Long-term
      outcomes including CMV disease, acute rejection, graft loss, patient survival,
      and seroconversion were assessed. RESULTS: At 2 years posttransplant, CMV disease
      occurred in significantly less patients in the 200- vs. the 100-day group: 21.3%
      vs. 38.7%, respectively (P<0.001). Between year 1 and 2, there were only 10 new
      cases of CMV disease; 7 in the 200-day group and 3 in the 100-day group. Patient
      survival was 100% in the 200-day group and 97% in the 100-day group (p=not
      significant). Biopsy-proven acute rejection and graft loss rates were comparable
      in both groups (11.6% vs. 17.2%, P=0.16, and 1.9% vs. 4.3%, P=0.22, in the 200
      day vs. 100-day groups, respectively). Seroconversion was delayed in the 200-day
      group but was similar to the 100-day group by 2 years posttransplant (IgM or IgG
      seroconversion; 55.5% in the 200-day group vs. 62.0% in the 100-day group at 2
      years; P=0.26). Assessment of seroconversion at the end of prophylaxis was of
      limited utility for predicting late-onset CMV disease. CONCLUSION: Extending
      valganciclovir prophylaxis from 100 to 200 days is associated with a sustained
      reduction in CMV disease up to 2 years posttransplant.

PMID- 21197714
TI  - Attention and executive functioning deficits in liver-transplanted children.
AB  - AIMS: Liver-transplanted children have an increased risk for serious
      developmental problems. We examined attention and executive functioning and their
      relation to intelligence and several disease-related variables after
      transplantation. METHODS: This is a monocentric, cross-sectional study with no
      reference group. Children's mean age at transplantation was 3.4+/-3.8 years
      (n=137, age 10.2+/-3.8 years). Assessment included attention and executive
      functioning (Test of Attentional Performance [TAP]/Test of Attentional
      Performance [children's version] [KITAP]) and intelligence (Wechsler Intelligence
      Scale for Children, 3rd edition/Kaufman Assessment Battery for Children).
      RESULTS: In most TAP and KITAP Subscales, children scored in the lower normal
      range, but reaction times, errors, and omissions were significantly below the
      population mean. Most notable deficits became manifest in the subscales Sustained
      Attention and Working Memory where 47% respectively 38% of the present sample
      scored below the normal range. Most TAP and KITAP Subscales, particularly
      Alertness and Go/NoGo, were highly correlated with Wechsler Intelligence Scale
      for Children, 3rd edition and Kaufman Assessment Battery for Children Subscales
      indicating that liver-transplanted children with longer reaction times display
      lower intelligence scores. Regression analysis revealed that decelerated reaction
      times in the subscales TAP-Go/NoGo, Divided Attention (KITAP and TAP), and KITAP
      Sustained Attention were associated with type of donation, duration of disease,
      age at transplantation, and sex (R2=0.14 to R2=0.25). CONCLUSION: Results provide
      evidence suggesting that liver-transplanted children are at risk of developmental
      deficits regarding attention and executive functioning. Especially intrinsic
      alertness and working memory performance seem to be insufficient. This might
      result in deficient initiating, sustaining, and controlling of action. In
      summary, results demonstrate the need for an early and comprehensive
      developmental screening after pediatric liver transplantation.

PMID- 21197716
TI  - Forensic medicine: a globally neglected branch.

PMID- 21197715
TI  - Magnetic resonance imaging of pancreatic islets transplanted into the liver in
      humans.
AB  - BACKGROUND: In vitro labeling of pancreatic islets by iron nanoparticles enables
      their detection as hypoitnense spots on serial magnetic resonance (MR) images. We
      report the first results of a pilot trial aiming to test the feasibility and
      safety of this technique in humans. METHODS: Islets were labeled in culture with
      5 MUL/mL ferucarbotran for 6 to 48 hr and transplanted into the portal vein (12
      infusions) in 8 C-peptide negative recipients. The liver area was examined the
      next day and 1, 4, and 24 weeks posttransplant using a 3T MR scanner. RESULTS: In
      all recipients, significant C-peptide levels and near-normal HbA1c values were
      achieved with 50% to 80% insulin dose reduction. No side effects related to the
      labeling procedure were documented. Typically, a significant islet spot number
      decrease (on average 60%) was detected at week 1 with subsequent only slight
      decrease for up to 24 weeks. In two subjects with labeling period of less than 6
      and 10 hr, only few islet spots were detected corresponding to poor islet
      visualization in phantoms labeled for the same period of time. CONCLUSION:
      Pancreatic islets (PI) visualization was safe and successful in all recipients
      but was less efficient if labeling period was less than 16 hr. Significant
      decrease of islet spots occurred at week 1, suggesting early islet destruction or
      impaired engraftment. Afterward, the islet spot numbers remained stable for up to
      24 weeks. Data show that MR detection of ferucarbotran-labeled islets enables
      their long-term noninvasive visualization and correlates with sustained C-peptide
      production.

PMID- 21197717
TI  - Federal actions. MR; Intellectual disability; federal laws.

PMID- 21197718
TI  - Deleware. Crimes against vulnerable adults.

PMID- 21197719
TI  - Delaware. Bill of rights; restraint; grievance procedures.

PMID- 21197720
TI  - Massachusetts & New Hampshire. Insurance; autism spectrum disorders.

PMID- 21197721
TI  - New Hampshire. SVP; attorney; multidisciplinary team.

PMID- 21197722
TI  - New York. Abuse or mistreatment; reporting.

PMID- 21197724
TI  - Proposed bachelor's degree in rural health care: an unmixed blessing for the
      rural population or for the graduate or neither?

PMID- 21197723
TI  - Seroprevalence of immunity to rubella in pregnant women.

PMID- 21197725
TI  - Expensive 'doorstops'. Placing BPA use in perspective.

PMID- 21197726
TI  - Medicare coding.

PMID- 21197727
TI  - [Women live longer: a distorting mirror?].

PMID- 21197728
TI  - [Impact of childhood immunization programs in 20th century France].

PMID- 21197729
TI  - [Your images. Q fever].

PMID- 21197730
TI  - [Relapsing pneumothorax in a young woman, revealing lymphangioleiomyomatosis].

PMID- 21197731
TI  - [Your images. Harlequin ichtyosis].

PMID- 21197732
TI  - [Colorectal cancer. How to decrease mortality by two?].

PMID- 21197733
TI  - [Epidemiology and screening of colon cancer].
AB  - Colon cancer is a major health problem in industrialized countries. It ranks at
      the first place among digestive cancers, with a sex ratio of 1. Colon cancer
      incidence increased between 1975 and 2005. France belongs to high risk countries
      for colorectal cancers. Since eighties, there was a progressive switch from left
      to right colon cancers. Owing to its frequency, and its epidemiological
      characteristics, colorectal cancer is, in France, justifiable of a national
      population-based mass screening. In France, national screening relies on biennial
      testing in subjects between 50 and 74 followed by total colonoscopy in case of
      positive test. In order to decrease significantly colorectal cancer mortality
      participation rate has to be over 50%. The colorectal cancer mortality decrease
      in this case varies between 15 and 28% in the general population, and between 33
      and 39% among participants to screening. On the basis of available data, the
      European Commission recommended organizing colorectal cancer screening in the EU.
      Colonoscopy screening is recommended for subjects at high risk, or very high risk
      for colorectal cancer.

PMID- 21197734
TI  - [Hereditary colorectal cancer].

PMID- 21197735
TI  - [Non-invasive imaging tools in colorectal cancer].
AB  - Coloscanner is a new radiologic tool to determine if abnormalities of colon and
      especially neoplasms are present. Considering its sensitivity and its tolerance,
      it could become in the next future a useful tool for screening of certain at risk
      populations. Positron emission tomography (PET) using fluorodeoxyglucose (18F) is
      the first functional imaging modality already available in oncology. In
      colorectal neoplasm, it is now considered as essential for the diagnosis of
      unexplained raise of CEA levels, differential diagnosis between benign and
      malignant disease (especially for suspected local recurrence of rectal cancer),
      or preoperative staging in case of complex surgical strategies. Its role in early
      determination of therapeutic response should be evaluated.

PMID- 21197736
TI  - [PET/CT in colorectal cancer].

PMID- 21197737
TI  - [Virtual colonoscopy].

PMID- 21197738
TI  - [Rectal cancer: which initial strategy?].
AB  - Surgery is the main treatment of rectal adenocarcinoma. After careful digital
      examination, rectoscopy and work-up, treatment decision is taken, in agreement
      with an informed patient according to the tumor stage. Early T1-2 tumors are
      treated with surgery first. Advanced T3-4 tumors are treated with pre-operative
      chemo-radiation often using the "CAP 50" regimen. At the present time, almost 60%
      of patients are definitively cured of their cancer with 75% being able to avoid
      permanent stoma. Pelvic relapses are seen in less than 6% of cases. In inoperable
      patients it is possible to cure a high percentage of early T1-2 tumors using
      external beam RT associated if possible with chemotherapy and 50 kv Contact X
      Ray.

PMID- 21197739
TI  - [Surgery in rectal cancer].

PMID- 21197740
TI  - [Operable colon cancer: initial strategy].
AB  - Individual screening of patients with personal or family history of colon cancer
      or polyps, or patients with an inflammatory condition of the digestive tract,
      combined with the generalization of mass screening using Hemoccult, have modified
      the way colon cancer is diagnosed. The optimization of colon surgery, together
      with adjuvant chemotherapy, has improved the 5- and 10-year survival. The five
      year survival rate is now comprised between 90 percent in patients with stage-I
      colon cancer, and 65-70 percent in patients with stage-III colon cancer. More
      than half patients suffer from stage-II (T3-T4 N0) or stage-III (TxN+) cancer,
      and 30 to 40 percent of these patients experience cancer recurrence without
      adjuvant therapy within 5 years following surgery. In patients with surgically
      resected colon cancer, these recurrences are mostly metastatic (liver, lungs,
      peritoneum), local recurrences remain uncommon. Metastases are secondary to
      microscopic tumor foci disseminated away from the primary tumor, non detectable
      before and during surgery. An adjuvant therapy combining oxaliplatin and
      fluoropyrimidine is clearly indicated in patients with stage-III colon tumor (20
      percent improvement of survival without recurrence), and can be considered in
      stage-III patients. This treatment is not indicated in patients with stage-I
      tumor.

PMID- 21197741
TI  - [Targeted therapies in colorectal cancer].
AB  - Since cancer biology is now better understood, molecular targets involved in
      tumorigenesis have been identified and specific "targeted therapy" has been
      designed. Antiangiogenic and anti-EGFR are the 2 targeted families of drugs
      introduced in the management of colorectal cancer. Bevacizumab, cetuximab and
      panitumumab are well tolerated and improve the pronostic of the patients in
      combination with conventional chemotherapy. Moreover, the mutation of KRAS gene
      has been recently identified as a predictive factor of resistance to anti-EGFR
      and allows a better selection of the patients. Formely based on 5FU, the
      management of advanced colorectal cancer is now involving a complex
      multidisciplinary strategy combining conventional chemotherapy, targeted agents,
      and surgery with curative intent whenever possible.

PMID- 21197742
TI  - [Biology applied to cancer treatments: the example of colorectal cancer].

PMID- 21197743
TI  - [Management of metastatic colorectal cancer].
AB  - The treatment of metastatic colorectal cancer has evolved significantly in recent
      years. Overall survival was significantly increased through the use of irinotecan
      and oxaliplatin, in combination with 5FU and leucovorin. More recently, new drugs
      directed against angiogenic factors or against an intracellular signaling pathway
      have demonstrated their effectiveness: bevacizumab (VEGF inhibitor) and cetuximab
      or panitumumab (inhibitors of EGF receptor) are the first molecules whose effect
      has been demonstrated in advanced colorectal cancer. Undoubtedly, advances in
      biology can both identify new targets, and therefore new treatments, but also
      better define patient groups most likely to get a benefit of these treatments.

PMID- 21197744
TI  - [Surgery of hepatic metastasis in colorectal cancers].

PMID- 21197745
TI  - [Colorectal cancer: what progress can we anticipate in the next few years?].
AB  - Colorectal cancer will remain a frequent cancer with an increasing incidence. Its
      prognosis will continue to improve because of the progress in the diagnostic and
      therapeutic procedures. Colorectal cancer screening will use better methods than
      the faecal occult blood test (FOBT) in the average risk population with
      biological technics easier, better accepted, more specific and more sensitive
      than the FOBT; the screening for high risk groups will also be helped by
      molecular biology and a better knowledge of the genetic profile of the families
      at risk. Efficacy and tolerance of chemotherapy regimens and targeted therapies
      will be better predicted by a more precise knowledge of the patients'
      pharmacogenetic profile and of their tumor molecular characteristics. Targeted
      therapies will be used in a more optimal way using more precise rules of
      prescription. These progresses will result in a higher rate of cure for
      metastatic patients favoured by an optimal combination of secondary surgery with
      all the effective technics for local and/or systemic treatments, and the respect
      of a strict multidisciplinary approach in specialized centers which are clearly
      warranted.

PMID- 21197746
TI  - [MEDLINE research. Interpreting query topics].

PMID- 21197747
TI  - [Hormone replacement therapy in France 5 years after the decrease in use].
AB  - Following the publication of the WHI randomized trial in 2002, a drastic decrease
      in Hormone Replacement Therapy (HRT) was observed due to an incredible publicity
      of the results of this trial and new recommendations from the drug agencies. The
      consequences of these rapid and important prescriptions of HRT are still not
      fully evaluated. A decrease in breast cancer incidence was however reported and
      discussed through over western countries. We present herein the actual types of
      HRT treatment used in France and report our interpretation of the decrease of
      breast cancer incidence.

PMID- 21197748
TI  - [A French exception. Transdermal postmenopausal hormone therapy].
AB  - Estrogens are still the main option for the treatment of climacteric symptoms,
      especially hot flashes. Their effectiveness is also demonstrated in the
      prevention of osteoporosis. If the results of the Women's Health Initiative
      showing an unfavorable risk/benefit balance of hormone replacement therapy with
      long-term use, the recent results of epidemiological studies analyzing
      transdermal estrogenotherapy suggest a best tolerance. Regarding venous
      thrombosis risk, many biological and epidemiological data suggest a safe
      tolerance of transdermal estrogens use. On the contrary, the risk of breast
      cancer and arterial does not appear to be modified by the route of administration
      of estrogens. Recent studies on colorectal cancer risks seem quite favorable to
      the transdermal route. These data are fundamental to assess the short-term risk
      benefit balance that appears on the current available data favorable to the
      transdermal route of administration.

PMID- 21197749
TI  - [Vascular risks and HRT].

PMID- 21197750
TI  - [Therapeutic alternatives for hot flashes in women with contraindications to
      HRT].

PMID- 21197751
TI  - [Oncologic risks associated with hormone replacement therapy].

PMID- 21197752
TI  - [Which treatment for osteoporosis in women with contraindication to HRT?].

PMID- 21197753
TI  - [Cognitive risks and HRT].

PMID- 21197754
TI  - [An equation in two variables].

PMID- 21197755
TI  - [Pathology of the salivary glands].

PMID- 21197756
TI  - [Nontraumatic spinal compression and cauda equina syndrome].

PMID- 21197757
TI  - [Suicidal risks in children, teenagers].

PMID- 21197758
TI  - [Sudden vision loss].

PMID- 21197759
TI  - [Medical responsibility: penal, civil, administrative and disciplinary].

PMID- 21197760
TI  - [Pharmacologic and non-pharmacologic treatments. Legal rules].

PMID- 21197761
TI  - [Madness in the century of Louis XIV].

PMID- 21197762
TI  - [The clinical role of high-sensitive troponin assays: update, interpretation, and
      perspectives].
AB  - More than thirty years have elapsed since the release of the first criteria of
      acute myocardial infarction defined by the WHO, but the diagnostic approach to
      the patients presenting with chest pain remains complex and controversial.
      Several diagnostic strategies have been proposed, characterized by a variety of
      algorithms and biochemical markers. The recent introduction of the new cardiac
      troponin assays, defined "highly-sensitive" and characterized by a higher
      analytic sensitivity, carries several advantages and some problems. These methods
      have allowed to identify the continuum of pathophysiological events ranging from
      an angina attack to the onset of a manifest myocardial infarction, as well as to
      drastically shorten the triage of the patients because minimum increments of the
      marker are appreciated much earlier than using the traditional assays. It is also
      predictable that the usefulness of these highly sensitive methods might be useful
      beyond the diagnosis of ischemic heart disease, especially for the prospective
      evaluation of the patients. Nevertheless, the drastic reduction of the diagnostic
      thresholds, which is a hallmark of this new generation of test, requires a more
      careful formulation of the reference intervals, a reassessment of the therapeutic
      strategies, and especially an accurate troubleshooting of the several causes of
      troponin abnormalities which are not associated with a clear clinical
      significance. In this context, a close partnership between the clinics and the
      laboratory is an essential aspect for the appropriate use of the tests and for
      the accurate interpretation of results.

PMID- 21197763
TI  - [Present trends and controversies in the use of beta-blockers in cardiovascular
      diseases].
AB  - In this paper we summarize present trends and controversies in the use of beta
      blockers in cardiovascular diseases. Beta-blockers are catecolamine competitive
      inhibitors and act through alpha and beta adrenergic receptors blockade.
      Different agents have a dose-dependent affinity for different beta adrenergic
      receptors (beta 1, beta 2, beta 3) which is less with higher doses. The most
      important therapeutic effects of beta-blockers are on cardiovascular system,
      where they act as negative chronotropic and inotropic agents, lowering cardiac
      work and improving oxygen demand /supply ratio. Clinical indications are
      numerous. For their anti-ischemic activity beta-blockers are used as anti-anginal
      drugs and in acute and previous myocardial infarction for preventing total and
      cardiovascular mortality. Combined use of beta-blockers and ACE inhibitors slows
      down heart failure progression and reduces cardiovascular mortality. Beta
      blockers are useful in treating focal atrial tachycardia and supra ventricular
      paroxysmal tachycardia, by reducing sinus node automaticity and delay atrio
      ventricular conduction; they also prevent sudden cardiac death and ventricular
      tachycardia associated with increased sympathetic activity. There is no
      indication in treating primary non-complicated hypertension with beta-blockers as
      first-line drugs. Different metabolic effects of selective and non-selective beta
      blockers are actually debated. In conclusion, beta-blockers have indication in
      the treatment of many cardiovascular diseases. Further studies are needed for
      better understanding the differences in cardiac and peripheral beta-blockers
      effects depending on their selectivity.

PMID- 21197764
TI  - [Vascular calcification in chronic kidney disease].
AB  - Patients affected by chronic kidney disease (CKD) suffer by secondary
      hyperparathyroidism and hyperphosphatemia. The new KDIGO guidelines identify a
      new definition in CKD-MBD (Mineral Bone Disorder), in which vascular
      calcification plays a central role. In fact, CKD patients that present vascular
      calcification have highest risk of cardiovascular morbility and mortality.
      Recently, it has been elucidated that the control of phosphate is one of the
      major problems for the nephrology community. Furthermore, new markers, such as
      FGF-23, have been identified as inducers of vascular calcification and
      cardiovascular disease in CKD. Therefore, the use of calcium-free phosphate
      binders may reduce the risk of cardiovascular disease by reducing both serum
      phosphate and FGF-23 levels.

PMID- 21197765
TI  - [Deficit of cell-mediated immunity and Nocardia's infection. A case report].
AB  - We described the case of a patient, recently studied, that underwent
      immunosuppressive therapy for pemphigus vulgaris and then developed a Nocardia's
      infection. The case was severe and multiple localization in lungs and other
      organs was observed. The pathology was treated by using antibiotics, without
      autoimmunity secondary pathology.

PMID- 21197767
TI  - [Building a benevolent relationship with a multi-handicapped adult].

PMID- 21197766
TI  - [Working in a specialized halfway house with handicapped persons].

PMID- 21197768
TI  - [Helping a multi-handicapped person at home].

PMID- 21197769
TI  - [Parents' journey, from handicapped child to adult].

PMID- 21197770
TI  - [Facilitating accessibility for handicapped persons].

PMID- 21197771
TI  - [Developing the therapeutic alliance in the nurse-patient relationship. Interview
      by Sylvie Warnet].

PMID- 21197772
TI  - [Care planning type by clinical pathways].

PMID- 21197773
TI  - [Postoperative analgesia by continuous surgical wound infiltration].

PMID- 21197774
TI  - [Trip to the country of plaster casts for skin diseases].

PMID- 21197775
TI  - [Value of a thesaurus of nursing best practices in chemotherapy].

PMID- 21197776
TI  - [Training in peripheral vein catheterization and contrast scanning].

PMID- 21197777
TI  - [The nurse and meningeal syndrome].

PMID- 21197778
TI  - [Personality disorders 2/4].

PMID- 21197779
TI  - [Therese Matter (1887-1975) and Eva Durrleman (1891-1993)].

PMID- 21197780
TI  - [Forty years of charity with the Claude Pompidou Foundation].

PMID- 21197781
TI  - [One must know what one wants with drug abuse tests in the workplace].

PMID- 21197782
TI  - [Drug abuse tests important part of preventive measures against narcotics. With
      testing drug abuse can be identified early in the workplace].

PMID- 21197783
TI  - [Male circumcision reduces HIV transmission. The risk of transmission from woman
      to man is halved].

PMID- 21197785
TI  - [Forehead or axillary temperature measurement is not reliable. Methods and
      thermometers compared with rectal temperature measurement as a reference].

PMID- 21197784
TI  - [Vitamin D deficiency in kidney failure. Risk factor for cardiovascular disease].

PMID- 21197786
TI  - [Acute management of epilepsy].

PMID- 21197787
TI  - [Chronic salicylate poisoning can give rise to pronounced metabolic alkalosis].

PMID- 21197788
TI  - [Treatment with methylphenidate in fatigue syndrome].

PMID- 21197789
TI  - [There are other and better alternatives to uterine donation].

PMID- 21197790
TI  - [Effective primary prevention requires special sociopolitical efforts!].

PMID- 21197791
TI  - [Are communication problems in health services taken seriously?].

PMID- 21197792
TI  - [Internal disc disruption (IDD)--an unknown diagnosis].

PMID- 21197794
TI  - Sport Rehabilitation and the Clinical and Translational Science Initiative.

PMID- 21197793
TI  - [Glenn Gould--piano virtuoso who escaped from his audience].

PMID- 21197795
TI  - Introduction to this special issue of Clinical and Translational Science.

PMID- 21197796
TI  - Exploring the significance of Polish shops within the Irish foodscape.
AB  - Since 2004, Polish food has become firmly embedded in the Irish foodscape as
      Polish shops opened up in cities and towns across Ireland. The aim of this
      article is to develop an understanding of the significance and meaning of these
      Polish shops within the Irish foodscape. In order to achieve this I will take a
      more-than-representational approach focusing on the practices, sensory reactions
      and material interactions Poles have within these stores and with their food
      products. The article will draw on ethnographic observations and semi-structured
      interviews with Polish migrants to explore their experiences. Attention to these
      details reveals how Polish shops become meaningful within the Irish foodscape for
      providing a sense of home to Polish migrants living in Ireland.

PMID- 21197797
TI  - The potato in Ireland's evolving agrarian landscape and agri-food system.
AB  - The scale, structure and impacts of food systems in Ireland have changed
      dramatically over the last several hundred years, predominantly since the
      mechanisation and intensification of farming began in the late nineteenth
      century. The transformation of the potato production system, which for the
      preceding century had dominated the Irish diet, was particularly dramatic. The
      time from the introduction of the potato c. 1600 to its catastrophic decline in
      the mid-1800s, represented a period of Irish agriculture distinctly at odds with
      what came before and after, involving as it did complete dependence on a single
      crop system. Despite devastating crop losses suffered in the nineteenth century
      and particularly associated with the Great Famine, the potato remained
      agriculturally significant in Ireland. From the late 1800s onwards the system
      underwent a transition towards the highly mechanised, specialised, intensive and
      market-oriented agri-industrial food systems of today. This new high input-high
      output system was accompanied by an expansion in environmental impacts extending
      from local to global scales. This article addresses that transition in the role
      and impacts of the potato in Ireland, from its introduction to the present day.

PMID- 21197798
TI  - Local food activity in the Republic of Ireland and Great Britain.
AB  - Recent changes in local food supply systems have attracted substantial research
      interest, but little consideration has been paid to exactly where they occur.
      This article combines data from three studies to compare local food system
      development in England, Wales, Scotland and Ireland using a single index of food
      relocalisation, thereby exploring the usefulness of the Index across different
      social and political contexts. Four diagnostic indicators suggest that local food
      systems in the south west of Ireland and Britain are particularly well developed.
      The Index itself is a useful tool for making international comparisons, being
      easy to replicate and allowing the integration of different data sets. Perhaps
      its greatest utility is that it opens up new avenues for further research.

PMID- 21197799
TI  - A quiet revolution? Beneath the surface of Ireland's alternative food
      initiatives.
AB  - Getting food to our plates has become a highly complex, industrialised and
      globalised process. However, transformations in how our food is supplied are not
      without resistance. Initiatives are emerging that take a step back to simpler,
      alternative methods of food supply, bringing the producer and consumer closer
      together. Alternative food initiatives which are commonly found in Ireland
      include allotments, community gardens, farmers' markets, farm shops and on-farm
      food enterprises. Understanding alternative food activities as a social movement
      can illuminate a fresh perspective on their nature and potential. While briefly
      considering the broad dynamics of alternative food activity in Ireland, this
      exploratory paper looks at the question of the nature of resistance and whether a
      collective vision may exist across initiatives, illustrated by two examples, a
      community garden and consumer food co-op. Finally some conclusions as to how
      alternative food initiatives may play a transformative role within the
      contemporary food system are discussed.

PMID- 21197800
TI  - An inventory of trees in Dublin city centre.
AB  - While urban areas are often considered to be comprised chiefly of artificial
      surfaces, they can contain a substantial portion of green space and a great
      diversity of natural habitats. These spaces include public parks, private gardens
      and street trees, all of which can provide valuable environmental services, such
      as improved air quality. Trees play a particular role in cities as they are often
      placed along roadsides and in the median strip of busy streets. As such they
      regulate access to sunshine, restrict airflow, provide shelter, scavenge air
      pollutants and manage noise at the street level. A tree planting policy can be an
      important part of a broader environmental strategy aimed at improving the quality
      of life in urban areas but this requires up-to-date knowledge of the current tree
      stock, which does not exist for Dublin. This article presents an inventory of
      trees in Dublin's city centre, defined as the area between the Grand and Royal
      canals. The results show that there are over 10,000 trees in the study area
      representing a density of 684 trees km-2 or one tree to approximately every 50
      residents of the city centre. The tree canopy extent when in full foliage was
      nearly 1 km2 in extent or 6% of the study area. A more detailed analysis of those
      trees planted along streets shows little species variation but clear distinction
      in the sizes of trees, which is indicative of the age of planting. These data are
      used to estimate the carbon stored in Dublin's trees.

PMID- 21197801
TI  - A comparison of symptoms after viewing text on a computer screen and hardcopy.
AB  - PURPOSE: Computer vision syndrome (CVS) is a complex of eye and vision problems
      experienced during or related to computer use. Ocular symptoms may include
      asthenopia, accommodative and vergence difficulties and dry eye. CVS occurs in up
      to 90% of computer workers, and given the almost universal use of these devices,
      it is important to identify whether these symptoms are specific to computer
      operation, or are simply a manifestation of performing a sustained near-vision
      task. METHOD: This study compared ocular symptoms immediately following a
      sustained near task. 30 young, visually-normal subjects read text aloud either
      from a desktop computer screen or a printed hardcopy page at a viewing distance
      of 50 cm for a continuous 20 min period. Identical text was used in the two
      sessions, which was matched for size and contrast. Target viewing angle and
      luminance were similar for the two conditions. Immediately following completion
      of the reading task, subjects completed a written questionnaire asking about
      their level of ocular discomfort during the task. RESULTS: When comparing the
      computer and hardcopy conditions, significant differences in median symptom
      scores were reported with regard to blurred vision during the task (t = 147.0; p
      = 0.03) and the mean symptom score (t = 102.5; p = 0.04). In both cases, symptoms
      were higher during computer use. CONCLUSIONS: Symptoms following sustained
      computer use were significantly worse than those reported after hard copy
      fixation under similar viewing conditions. A better understanding of the
      physiology underlying CVS is critical to allow more accurate diagnosis and
      treatment. This will allow practitioners to optimize visual comfort and
      efficiency during computer operation.

PMID- 21197803
TI  - Simultaneous measurement of objective refraction, accommodation response and
      axial length of the human eye.
AB  - PURPOSE: Accurate measurements of ocular biometry and objective refraction are of
      vital importance to research laboratories working in the area of refractive error
      development and oculomotor function. A number of commercially available
      instruments can provide these measurements, and are used in both their intended
      modes, and with modifications to increase their research utility. A limitation
      that exists currently is the inability to conduct simultaneous measurements of
      refractive error or accommodation response, and the axial length of the same eye.
      In this technical note we provide details of a method to adapt the Zeiss
      IOLMaster and the Shin-Nippon SRW-5000 infrared optometer to simultaneously
      measure refraction and axial length. METHODS: The optical modification used to
      combine the measurement paths of the IOLMaster and SRW-5000 instruments consists
      of a narrow band-pass filter, and optical relay to extend the working distance of
      the IOLMaster, and an electronic system to provide synchronisation between the
      IOLMaster and the SRW-5000 continuous accommodation recording system. The optical
      modification was tested on model eyes, and on a cohort of 20 human eyes. The
      combined system was then used to measure accommodation response and axial length
      simultaneously in a single participant. RESULTS: Inclusion of the optical
      modification in the IOLMaster pathway induced a 0.004 mm shift in the average
      measurement of a calibration eye, and an average difference of 0.001 mm for a
      cohort of human eyes. For the SRW-5000, inclusion of the modified optics induced
      a +0.15 D shift in the spherical component of refraction measurements made on a
      model eye, and an average shift of +0.12 D in the spherical component of
      measurements made on a cohort of human eyes. Simultaneous measurement of
      accommodation response and axial length in a single participant revealed that a
      change in stimulus vergence from 0 to 5 D caused an average accommodation
      response of 3.89 D, and an average transient axial length change of 0.059 mm.
      CONCLUSIONS: The system described provides a useful method of achieving
      simultaneous measurements of axial length, objective refraction and accommodation
      response in a human eye.

PMID- 21197804
TI  - More than a mermaid: Esther Williams, performance, and the body.

PMID- 21197805
TI  - Sculpted landscapes: art & place in Cleveland's Cultural Gardens, 1916-2006.
AB  - Perhaps the world's first peace garden, the Cleveland Cultural Gardens embody the
      history of twentieth-century America and reveal the complex interrelations
      between art and place. This essay uses the Cleveland Cultural Gardens as a lens
      through which to explore how art and place have intersected over time. It
      explores how communities have negotiated questions of national, ethnic, and
      American identity and embedded those identities into the vernacular landscape. It
      considers how the particulars of place were embedded into a public garden and
      asks whether it is possible for public art to transcend its place-both in terms
      of geography and history. In some sense, the Gardens have transcended their
      place, but in others respects, their fortunes were bound inextricably to that
      place, to the economic, demographic, and cultural contours that shaped and
      reshaped Northern Ohio. As works of art, the Cleveland Cultural Gardens both have
      reflected the history of Cleveland and American industrial cities during the 20th
      century and revealed something of the dynamics that underscored the changing
      character of public art and gardens in American cities.

PMID- 21197806
TI  - Microcosms of democracy: imagining the city neighborhood in World War II-era
      America.
AB  - This essay sketches the rise of a Popular Front-inflected vision of the U.S. city
      neighborhood's meaning and worth, a communitarian ideal that reached its zenith
      during World War II before receding in the face of cold-war anxieties, postwar
      suburbanization, and trepidation over creeping blight. During the war years,
      numerous progressives interpreted the ethnic-accented urban neighborhood as place
      where national values became most concrete, casting it as a uniquely American
      rebuff to the fascist drive for purity. Elaborations appeared in the popular
      press's celebratory cadences, in writings by educators and social scientists such
      as Rachel DuBois and Louis Wirth, and in novels, plays, and musicals by Sholem
      Asch, Louis Hazam, Kurt Weill, Langston Hughes, and others. Each offered new ways
      for making sense of urban space, yet their works reveal contradictions and
      uncertainties, particularly in an inability to meld competing impulses toward
      assimilation and particularism. Building on the volume's theme "The Arts in
      Place," this essay examines these texts as a collective form of imaginative
      "placemaking." It explores the conflicted mode of liberal nationalism that took
      the polyglot city neighborhood as emblem. And it outlines the fissures embedded
      in that vision, which emerged more fully as the provisional wartime consensus
      dissolved.

PMID- 21197807
TI  - Streets and stages: urban renewal and the arts after World War II.
AB  - Lincoln Center for the Performing Arts in Manhattan and the revitalization of the
      Brooklyn Academy of Music in Brooklyn offer insights into the intersection of
      arts and urbanization after World War II. This intra-city comparison shows the
      aggrandizing pull of the international arena in the shaping of Lincoln Center and
      the arts it featured in contrast to the local focus and debate that transformed
      how BAM fit into its Brooklyn neighborhood. The performing arts, bound as they
      are to a moment fused in space and time, reveal the making of place within
      grandiose formal buildings as well as outside on the streets that surround them
      and it is, perhaps, that tensile connection between stages and streets that
      informs the relevancy of both the institution and the arts it features. At a time
      when the suburbs pulled more and more people, the arts provided a counterforce in
      cities, as magnet and stimulus. The arts were used as compensation for the
      demolition and re-building of a neighborhood in urban renewal, but they also
      exposed the more complex social dynamics that underpinned the transformation of
      the mid-20th century American city from a segregated to a multi-faceted place.

PMID- 21197808
TI  - "No fertile soil for pathogens": rayon, advertising, and biopolitics in late
      Weimar Germany.
AB  - Recent research on twentieth-century German history has begun to re-examine the
      centrality of race as a category of analysis. While not discounting its
      importance in the shaping and enacting of Nazi policies and practices, race is
      seen instead as one among many factors leading to the crimes of the Nazi regime.
      In this paper, the author considers the role consumerist desires and fantasies
      played in the wider context of the inter-war European fascination with notions of
      technology, "hygiene," democracy, and modernity. Using advertisements that were
      created to promote manufactured-fiber (rayon) apparel, this article suggests that
      continuities across cultures and time periods necessitate a re-evaluation of race
      as the signal organizing principal. Instead, the author argues that by
      complicating the intersections between class, science and technology, and an
      emerging, but troubling, modernity, 1920s rayon advertising offers an especially
      rich site for analysis of the ways in which biopolitics and nascent consumerism
      both sold products and constructed ideologies before 1933, and influenced the
      post-war welfare state.

PMID- 21197809
TI  - Sometimes a stamen is only a stamen: sexuality, women and Darwin's "Loves of the
      Plants".

PMID- 21197810
TI  - The use and misuse of Level IV and Level V evidence.

PMID- 21197811
TI  - State of literature in foot and ankle.

PMID- 21197812
TI  - Is good outcomes research really better than personal experience and Level V
      evidence.

PMID- 21197813
TI  - At last, our third national oral health survey.

PMID- 21197814
TI  - Work experiences, professional development and career prospects of New Zealand
      dental house surgeons.
AB  - OBJECTIVE: New dental graduates compete for house surgeon positions every year,
      despite little being known about the work experience gained from such posts. The
      main objectives of this study were to identify the nature of house surgeons' work
      experiences, their continued professional development (CPD) opportunities and the
      impact of hospital experience on their future career pathways. METHOD: A
      questionnaire was mailed to all 31 New Zealand dental house surgeons (response
      rate 100%). RESULTS: The majority of house surgeons (77.4%) found hospital work
      enjoyable, with nearly all (93.5%) perceiving themselves as better clinicians
      from their experience. Oral surgery, restorative dentistry, special needs
      dentistry and removable prosthodontics were the most commonly practised areas.
      The average weekly number of working hours was 42.3 hours for a normal week and
      61.8 hours for an on-call week. Stress levels during on-call work were
      significantly higher than during day-to-day hospital work (p < 0.05).
      Departmental seminars were reported to be the most common form of CPD available
      at hospitals (74.2%), followed by hands-on clinical training (61.3%). More than
      half of the house surgeons (58.1%) planned to pursue a specialist career, with
      nearly 13% wishing to return to a New Zealand hospital in the future.
      CONCLUSIONS: A dental house surgeon position remains an attractive choice and
      offers an enjoyable experience for young graduates. Hospitals provide ample CPD
      opportunities and appear to play an influential role in a house surgeon's career
      pathway.

PMID- 21197815
TI  - Non-syndromal orofacial clefts in the Canterbury/West Coast region during the
      2000-2009 period.
AB  - OBJECTIVES: To describe the incidence and ethnic characteristics of orofacial
      clefting in the Canterbury/West Coast region over the ten-year period 2000-2009
      and compare it with previously-reported data. DESIGN: A retrospective analysis of
      case-series data. SETTING: Cleft clinic, Oral Health Centre, Christchurch
      Hospital. PARTICIPANTS: All babies born in the Canterbury/West Coast region from
      1 January 2000 to 31 December 2009 with a non-syndromal orofacial cleft were
      included. RESULTS: The calculated incidence of non-syndromal orofacial clefts was
      1.69 per thousand live births, comprising 0.85 for cleft lip with or without
      cleft palate (CL[P]) and and 0.84 for isolated cleft palate (CP). The earlier 40
      year data estimated an incidence of 1.94 per thousand live births made up of 1.13
      CL[P] and 0.81 CP. Maori and non-Maori had a similar incidence of CL[P]; however,
      it appears that Maori had a much higher incidence of CP than non-Maori (incidence
      of 1.35 and 0.88 per thousand live births respectively). CONCLUSIONS: The
      incidence of CL[P] has decreased while that of CP has remained constant. The
      incidence of CP in Maori is higher than in non-Maori.

PMID- 21197816
TI  - Assessing children's dental anxiety in New Zealand.
AB  - OBJECTIVES: To investigate the reliability and validity of computerized anxiety
      assessment with New Zealand children, and to explore children's preferences for
      the method of anxiety assessment. DESIGN: A validation study including test
      retest reliability, and mean anxiety scores for items on the computerised Smiley
      Faces Program-Revised scale (SFP-R), together with qualitative data on children's
      preferences following two computer assessments and a pen-and-paper assessment
      using the Modified Children's Dental Anxiety Scale. PARTICIPANTS: 206 children
      ranging in age from five to 13 years and from from three primary schools (one
      each of high, medium and low decile ranking). Approximately one-third (33%) were
      European, one-quarter M&ori or Polynesian, and 38% were Asian. RESULTS: Estimates
      of internal consistency, (calculated using Cronbach's alpha), demonstrated an
      acceptable level of reliability for the SFP-R (alpha = 0.75). Test-retest data
      from the sub-sample of children across a two-week period showed a strong
      correlation (r = 0.75, p < 0.001). The SFP-R was found to significantly correlate
      with the MCDAS demonstrating concurrent validity (r = 0.67, p < 0.01). The mean
      anxiety score for all children was 19.9 (SD = 6.1). A two-way analysis of
      variance was employed to test for the effect of gender and age on total dental
      anxiety scores. There was no main effect for gender (F(1, 195) = 0.017, p > 0.05)
      or age group (F(3, 195) = 1.527, p > 0.05) and no interaction between the two
      factors. Children rated themselves most anxious when faced with the drill (mean =
      4.5, SD = 1.7). 'Happy' faces were chosen some of the time for all of the items,
      even for the invasive procedures. CONCLUSIONS: The SFP-R demonstrated good
      reliability and validity with New Zealand children and data indicated that it is
      a stable measure over time. It demonstrated concurrent validity, as evidenced by
      the moderately strong correlation with the MCDAS. Mean scores and frequency data
      suggest that, as there is still a significant proportion of children with very
      high overall anxiety scores, dental anxiety should be formally assessed and
      managed in NZ children. Children's preferences were for the computerised
      assessment of dental anxiety, supporting the continued development of Dental
      Jungle, the New Zealand dental anxiety intervention program.

PMID- 21197817
TI  - ACC claims for sports-related dental trauma from 1999 to 2008: a retrospective
      analysis.
AB  - OBJECTIVE: To describe trends in sports-related dental injuries reported to ACC
      in the past 10 years. DESIGN: Retrospective case series. METHODS: De-identified
      data on orofacial injuries were obtained from ACC for the financial years 1999
      2008, and new claims were identified for each year (with recurring claims omitted
      from the analysis). Patterns in new-claim data were identified by age, sex,
      region and the sport involved. Trends in claims for the sport categories were
      also identified RESULTS: The annual number of claims ranged from 24,998 to
      31,257; overall, 38.7% of claims were made by females and 61.3% by males, and
      these proportions remained largely unchanged during the observation period. For
      sports-related claims, those aged 11-20 years had the highest percentage of
      claims (with between 41.7% and 44.4%, depending on year) while those older than
      60 had the smallest percentage of claims, with 0.5% to 1.1%. Sport was involved
      in 20.6% to 26.2% of new claims. The highest percentage of injuries was
      attributable to rugby (between 22.2% and 33.1%, depending on the year). Water
      sports contributed to between 14.2% and 20.8% of claims. Cycling increased from
      1.5% in 1999 to 15.3% in 2006, and then decreased to 10.6% in 2008. Hockey,
      basketball, soccer, cricket and netball had 4.4%, 4.8%, 6.9%, 4.7% and 3.9%
      respectively. CONCLUSIONS: Although its share has decreased in recent years,
      rugby remained the greatest contributor to sport-related orofacial injuries, with
      water sports consistently second (cycling had the largest change, with a rapid
      increase in the past 3 years). There is a need to re-examine mouthguard (and
      other injury prevention) policies for particular sports.

PMID- 21197818
TI  - The ongoing struggle of Haiti's nursing profession.

PMID- 21197819
TI  - EXTRA help bringing change to the workplace.

PMID- 21197820
TI  - The army nurse. 1911.

PMID- 21197821
TI  - Ontario leads the way. NP-led clinics:.

PMID- 21197822
TI  - Patient decision aids help answer "what's best for me?".

PMID- 21197823
TI  - Earning trust and building strength.

PMID- 21197824
TI  - A healthier health system is ours to create.

PMID- 21197825
TI  - Accountability and equality are a motivating force for Diane Abbott.

PMID- 21197826
TI  - Slow and steady wins.
AB  - All nurses and healthcare assistants in one trust receive mandatory education in
      falls prevention. The number of falls has decreased by more than 10 per cent as a
      result.

PMID- 21197827
TI  - Local health care steps into a new era.
AB  - This article introduces a four-part series on the future of community services in
      England. The series will explore different models of delivery.

PMID- 21197828
TI  - Lending a little hand.
AB  - Uncertainty among parents and health professionals about what toddlers should be
      eating has resulted in advice from the Infant and Toddler Forum.

PMID- 21197829
TI  - The palliative care that never came.

PMID- 21197830
TI  - Faulty goods.

PMID- 21197831
TI  - Acute pain management in the opioid-tolerant patient.
AB  - The main goals in treating acute pain in opioid-tolerant patients are effective
      pain relief and prevention of withdrawal symptoms. This article provides an
      overview of the issues that practitioners need to consider when caring for
      potential and actual opioid-tolerant patients experiencing acute pain, for
      example following surgery or injury. It highlights the importance of a multimodal
      analgesic approach to pain control and the prevention of withdrawal. It defines
      the terminology used in managing opioid-tolerant patients in order to allay
      healthcare professionals' misconceptions.

PMID- 21197832
TI  - Mean arterial blood pressure and the assessment of acutely ill patients.
AB  - This article discusses the role of vital sign data collection in the acute
      setting when assessing patients at risk of or actually clinically deteriorating.
      Specifically, the article focuses on explaining the important concepts of mean
      arterial blood pressure and pulse pressure as indicators of clinical
      deterioration.

PMID- 21197833
TI  - An overview of permanent cardiac pacing.
AB  - A permanent cardiac pacemaker is an implantable device that maintains the
      patient's heart rate by electrically stimulating the heart muscle when the
      natural regulating mechanisms fail. This article focuses on the indications for
      permanent cardiac pacing, general technical concepts and care of the patient
      undergoing this procedure.

PMID- 21197834
TI  - Bone fractures.

PMID- 21197835
TI  - Learn through role play.

PMID- 21197836
TI  - Model for success.

PMID- 21197837
TI  - The hub of the matter.

PMID- 21197838
TI  - Swiss biotech--an overview of the industry and the key stakeholders 2010.
AB  - This article presents the stakeholders of the Swiss Biotechnology sector. From
      academia to industry, from TechTransfer initiatives to state impulse programs,
      the sector has developed rapidly in the last years. Public Private Partnerships
      such as Life Science Clusters and collaborations between industry associations
      have proven to be an essential part for sustainable success for our national GDP.
      The author has extensive experience in the various sub-sectors.

PMID- 21197839
TI  - Swiss Industrial Biocatalysis Consortium (SIBC).
AB  - Taking up the common challenges in biocatalysis, a group of industrialists
      decided to react with a bottom-up solution, and created the Swiss Industrial
      Biocatalysis Consortium (SIBC). The Swiss Industrial Biocatalysis Consortium is a
      pre-competitive working group to better implement and utilize existing know-how
      and resources in biocatalysis, and to influence and shape the economic and
      educational political environment. Recent examples of activities are outlined.

PMID- 21197840
TI  - Culture collections and the biotechnology deal.
AB  - Culture collections provide starting material for life science research,
      development and production. Especially in biotechnology, well characterised and
      pure microbial strains are essential for reproducible and safe bioprocesses.
      Culture collections also play a role as repositories of biological material for
      future applications and help to preserve biological diversity. In addition, they
      also maintain the know-how needed for more complex identification methods and
      help to develop new techniques. To enable culture collections to achieve higher
      quality standards, new certification guidelines for biological resource centres
      are currently being developed.

PMID- 21197841
TI  - Application of activated charcoal in the downstream processing of bacterial
      olefinic poly(3-hydroxyalkanoates).
AB  - Medium chain length poly(hydroxyalkanoates) (mcl-PHAs) are bacterial
      thermoplastic elastomers with a large potential in medical applications. The
      present study provides a novel process to isolate and purify poly([R]-3-hydroxy
      omega-undecenoate-co-3-hydroxy-omega-nonenoate-co-3-hydroxy-omega-heptenoate)
      (PHUE) and poly([R]-3-hydroxy-omega-undecenoate-co-3-hydroxy-omega-nonenoate-co-3
      hydroxyoctanoate-co-3-hydroxy-omega-heptenoate-co-3-hydroxyhexanoate) (PHOUE)
      from Pseudomonas putida species. Three different types of activated charcoal were
      compared with regard to their capability to selectively remove impurities. The
      product 'Charcoal activated, powder, pure' from Merck was found to be most
      suitable. Using ethyl acetate as solvent, the polyesters were extracted from
      freeze-dried biomass at room temperature and simultaneously purified by addition
      of activated charcoal at the beginning of the extraction. The period of
      extraction was one hour and the ratio solvent to biomass was 15:1 (vol/wt). After
      extraction, the solids were separated by pressure filtration through a metallic
      lace tissue. The filtrate was again passed through the previously accumulated
      filter cake, followed by a second filtration through a 0.45 microm membrane to
      remove finest coal particles. The resulting filtrate was concentrated, thus
      yielding polyesters whose quality and yield depended on the quantity of activated
      charcoal applied. For highly pure PHUE and PHOUE with low endotoxin levels, the
      optimum ratio of activated charcoal to solvent for extraction (V/V) was found to
      be 0.5 for PHUE and 0.25 for PHOUE. The yields with regard to the raw polymers
      amounted to 55 wt% for PHUE and 75 wt% for PHOUE, which are acceptable for
      polymers that can be used for medical applications.

PMID- 21197842
TI  - IMAPlate based miniature, high sensitive, rapid screening method for detecting
      bioengineered, secreted lipase activities in yeast expression systems.
AB  - A spectrophotometric assay based on a miniaturized 96-well plate device
      (IMAPlate) enables a rapid and simple screening of bioengineered recombinant
      lipases expressed and secreted by Saccharomyces cerevisiae. Starting from a
      colony, the test delivers a quantitative estimation of enzymatic activity titer
      in 24 h or less with manual high throughput performances.

PMID- 21197843
TI  - Development and characterization of an enzymatic method for the rapid
      determination of gamma hydroxybutyric acid.
AB  - Gamma hydroxybutyric acid (GHB) is a regulated therapeutic drug, which naturally
      occurs in mammalian brain tissues as an intermediate of the GABA (gamma
      aminobutyric acid) neurotransmitter metabolism. The increasing misuse of GHB as a
      narcotic or abusing drug in recent years calls for the development of a simple
      and rapid screening method as an alternative to the currently available,
      technically demanding diagnostic methods. We have developed a rapid enzymatic
      assay based on the GHB dehydrogenase of Ralstonia eutropha. The enzyme is
      expressed as a recombinant protein in Escherichia coli and characterized in terms
      of reaction mechanism and kinetic parameters for the catalysis of conversion of
      GHB into succinic semialdehyde (SSA). The concomitant NADH production enables
      spectrophotometric monitoring of the reaction and the quantification of GHB in
      physiological fluids depending on initial velocities. We have tested a panel of
      twelve serum and urine samples containing GHB concentrations from 0.0 to 2.1
      mmol/L. GHB dehydrogenase activity obeys a non classical bi bi ping pong
      mechanism exhibiting substrate inhibition by NAD+. With an optimal NAD+
      concentration of 3.7 mmol/L in the reaction, the enzyme yields a K(M) of 1.0
      mmol/L for GHB and a Vmax of 3.37 mmol/min/mg. The assay shows a linear standard
      curve from 0.1 to at least 1 mmol/L of GHB. Spiking experiments result in mean
      recoveries of 92% for urine and 114% for serum, respectively. The comparison to
      an ion chromatographic reference method exhibits a mean difference of 10%
      divergence from the target values in urine and 9% in serum, respectively.

PMID- 21197844
TI  - Continuous micro-production using enzymatic reaction and online monitoring.
AB  - A micro-reactor coupled to a microfluidic system and an online UV/VIS
      spectrometer is described. The enzymatic reaction studied is the hydrolysis of
      the N-benzoyl-L-tyrosine ethyl ester (BTEE) to N-benzoyl-L-tyrosine (BT) and
      ethanol, catalyzed by chymotrypsin. The production is online monitored with UV
      spectroscopy at 256 nm. Three different immobilization methods of the enzyme are
      discussed: Eupergit C, controlled-pore glass (CPG), and Sepharose.

PMID- 21197845
TI  - Process monitoring with disposable chemical sensors fit in the framework of
      process analysis technology (PAT) for innovative pharmaceutical development and
      quality assurance.
AB  - The innovative principle of enzymatic sensors applied to monitor the feeding
      process in disposable bioreactors is described. Innovative is the type of enzyme
      immobilized within the 'paste' to monitor L-glutamate. Innovative is the
      application of the miniaturized disposable sensor developed at C-CIT AG for
      continuous monitoring. The sensor allows the amount of the digested nutrient to
      be estimated from the amperometric signal. Innovative is the wireless signal
      transduction between the sensor mounted to the bioreactor and the signal
      receiver. An example of a process control run is given and, also, the
      biocompatibility and the specifications of the biosensors. The comparison of
      results evaluated by different analytical methods is discussed.

PMID- 21197846
TI  - Tissue engineering--the gateway to regenerative medicine.
AB  - Tissue engineering as an emerging biotechnology sector aims at the in vitro
      regeneration of diseased tissues and promises to profoundly change medical
      practice, offering the possibility of regenerating tissues and organs instead of
      just repairing them (regenerative medicine). Improved healing processes and a
      higher quality of life are the expected results. This article gives an overview
      of different technologies for regenerative medicine and presents results of our
      own current applied research and development. A recent project was successfully
      closed with the development of a natural biomaterial for soft tissue oral
      defects. The establishment of an in vitro bioreactor system enabled us to
      simulate the mechanical and biological environment in a healing wound and to
      investigate the suitability of different implant materials for the oral tissue
      regeneration. Moreover, focusing the attention on an alternative method for the
      intervertebral disc (IVD) regeneration, we established a new tissue engineered
      approach, based on the three-dimensional (3D) culture of autologous human IVD
      cells into a polyurethane (PU)-fibrin composite. IVD cells were able to
      proliferate and, thanks to the 3D conditions, to differentiate expressing the
      typical native tissue markers. The development of an automated platform was the
      goal of an additional project, to standardize the cell culture technology,
      increase the bio-safety and reduce the production costs, moving tissue
      engineering nearer to clinical application.

PMID- 21197847
TI  - Recombinant yeast technology at the cutting edge: robust tools for both designed
      catalysts and new biologicals.
AB  - Health and safety concerns, enhanced quality criteria, and environmental
      sustainability, have prompted investigations into production using recombinant
      yeasts as a feasible alternative for isolation of proteins from natural animal or
      plant sources, as well as for processes utilising either mammalian cell cultures
      or bacterial systems. An overview of recent research papers and review articles
      provides readers with a comprehensive insight into the field of next-generation
      yeast expression systems. Major breakthroughs in recombinant yeast technology
      linked to Pichia pastoris are (i) the public availability of tools to generate
      proteins with tailored and highly homogenous N-glycan structures, similar to the
      forms assembled in humans, (ii) the recent accomplishment of the annotation of
      its genome sequence, and finally, (iii) the presence of the first few (non
      glycosylated) therapeutic proteins in Pichia on the market. The P. pastoris
      expression platform is now well developed, as proven by multiple products used in
      human and veterinary medicine and in industry (e.g., enzymes for chemical
      synthesis and for the modification/synthesis of pharmaceuticals, drug target
      proteins used for structural analysis or for high throughput screening, proteins
      for diagnostics, proteinous biomaterials, vaccines, and therapeutic proteins).
      Nevertheless, the complexity of protein analysis (monitoring) continues to
      restrict process development for recombinant products. Drawing on combined
      expertise in molecular biology and process technology, the Institute of
      Biotechnology (IBT) at the Zurich University of Applied Science (ZHAW) and its
      international partners have developed solutions which (i) fully eliminate (or
      partially reduce) the use of methanol, which is undesirable in high-cell-density
      and high-productivity processes, (ii) match both strain construction and process
      design with the target protein characteristics to the benefit of the cells'
      physiological shape, and (iii) allow multi-gene expressions to be balanced to
      achieve custom tailored and reproducible protein quality at the level of
      (engineered) posttranslational modifications. In addition to enabling superior
      product quality specifications to be achieved with reduced development time,
      these innovations have helped the industries involved to minimise financial risks
      and the risk of failure, as well as create an opportunity for (new) drugs with
      improved functionality at low cost.

PMID- 21197848
TI  - Innovative, non-stirred bioreactors in scales from milliliters up to 1000 liters
      for suspension cultures of cells using disposable bags and containers--a Swiss
      contribution.
AB  - Innovative mixing principles in bioreactors, for example using the rocking of a
      platform to induce a backwards and forwards 'wave', or using orbital shaking to
      generate a 'wave' that runs round in a cylindrical container, have proved to be
      successful for the suspension cultures of cells, especially when combined with
      disposable materials. This article presents an overview of the engineering
      characteristics when these new principles are applied in bioreactors, and case
      studies covering scales of operation from milliliters to 1000 liters.

PMID- 21197849
TI  - Nitrocatechol dispersants to tailor superparamagnetic Fe3O4 nanoparticles.

PMID- 21197850
TI  - Decompression sickness risk at 6553 m breathing two gas mixtures.
AB  - INTRODUCTION: The risk of severe decompression sickness (DCS) increases rapidly
      above 6248 m (20,500 ft) and is greater when breathing higher proportions of
      inert gas. Contemporary aircrew may be exposed to higher cabin altitudes while
      breathing molecular sieve oxygen concentrator (MSOC) product gas containing
      variable concentrations of oxygen, nitrogen, and argon. This study assessed the
      risk of DCS at 6553 m (21,500 ft) breathing two simulated MSOC product gas
      mixtures. METHODS: In a hypobaric chamber, 10 subjects each undertook 2 4-h
      exposures at 6553 m breathing either 75% O2:21% N2:4% Ar or 56% 02:42% N2:2% Ar.
      Subjects undertook regular activities simulating in-flight movements of fast jet
      aircrew. Venous gas emboli (VGE) "bubble" load was graded every 15 min using 2D
      and Doppler echocardiography by experienced operators blinded to breathing gas
      composition. RESULTS: DCS occurred in five exposures (25%), the earliest after
      less than 90 min at altitude. All were minor, single-site, uncomplicated limb
      bends that resolved with recompression. VGE occurred in 85% of exposures with
      some early-onset, heavy loads. Survival (Probit) analysis indicated that
      breathing 56% oxygen significantly decreased VGE latency relative to breathing
      75% oxygen (relative potency 3.05). CONCLUSIONS: From 20 experimental exposures,
      the risk of DCS at 6553 m is estimated at 5% by 90 min and 20% at 3 h. Exploiting
      the negative predictive value of VGE latency as a surrogate measure of protection
      from DCS, at high cabin altitudes better MSOC performance (higher product gas
      oxygen concentrations) will protect more aircrew for longer.

PMID- 21197851
TI  - Rat intervertebral disc health during hindlimb unloading: brief ambulation with
      or without vibration.
AB  - BACKGROUND: Changes in intervertebral disc (IVD) morphology and biochemistry have
      been characterized only incompletely in the rat hindlimb unloading (HLU) model.
      Here we present preliminary data on the differential effects of short periods of
      weight-bearing with or without low-level whole-body vibrations (WBV) on the
      lumbar rat IVD during HLU. METHODS: Rats were subjected to HLU and exposed to
      daily periods (15 min x d(-1)) of either ambulatory activities (HLU+AMB) or whole
      body vibrations superimposed upon ambulation (HLU+WBV; WBV at 45 Hz, 0.3 g).
      RESULTS: At the end of the 4-wk experimental period and compared to age-matched
      control rats (AC), the lumbar IVD of HLU+AMB had a 22% smaller
      glycosaminoglycans/collagen ratio, 12% smaller posterior IVD height, 13% smaller
      cross-sectional area, 9% greater ratio of height/area, and a 24% smaller volume
      of the surrounding muscle tissue. Compared to HLU+AMB rats, the addition of low
      level vibratory loading did not significantly alter IVD biochemistry, posterior
      height, area, or volume but normalized muscle volume (-8% vs. AC) and the IVD
      height/area ratio (-3% vs. AC) to levels similar to normal controls. Relative to
      AC, superposition of the vibratory stimulus onto ambulation had a greater effect
      on IVD area than on IVD height. IVD volume and IVD posterior height of HLU+WBV
      rats remained 13% and 16% smaller than in normal controls. CONCLUSION: Even
      though neither intervention was successful in preventing hindlimb unloading
      induced changes in IVD volume, compared to ambulation alone, very low-level whole
      body vibrations resulted in greater total back and abdominal muscle volume and
      directionally altered IVD geometry.

PMID- 21197852
TI  - Aerobic exercise capacity and muscle volume after lower limb suspension with
      exercise countermeasure.
AB  - INTRODUCTION: The purpose of the present study was to elucidate the effect of
      unilateral lower limb suspension (ULLS) on aerobic capacity during one-legged
      cycle exercise and whether the change in aerobic exercise capacity after ULLS
      with or without intensive interval training is related to the change in skeletal
      muscle volume. METHODS: There were 13 young men who underwent 20 d of ULLS and
      were divided into 2 groups based on some physical characteristics: the control
      group (CON; N=7) and the trained group (TRN; N=6). Subjects in TRN underwent
      interval cycle training on alternate days during ULLS. The respiratory and
      circulatory responses to one-legged incremental cycling and muscle volume of the
      thigh were measured before and after 20 d of ULLS. RESULTS: : One-legged peak
      oxygen uptake (VO2peak) and total muscle volume of the thigh in CON decreased
      significantly after 20 d of ULLS (-11.0 +/- 3.5% in VO2peak, -6.1 +/- 1.8% in
      total muscle volume). However, these parameters were maintained in TRN (+0.2 +/-
      5.2% in VO2peaka, -1.0 +/- 1.8% in total muscle volume). Circulatory variables at
      rest and during submaximal exercise were unchanged in both groups after ULLS.
      Changes in one-legged VO2peak were significantly correlated with change in total
      muscle volume of the thigh in CON. CONCLUSION: Our findings indicated that
      peripheral adaptations after ULLS could relate to the change in aerobic exercise
      capacity during one-legged exercise. Our results also suggest that intensive
      interval training prevents ULLS-induced deconditioning of both aerobic exercise
      capacity and skeletal muscle volume.

PMID- 21197853
TI  - Locomotion in simulated and real microgravity: horizontal suspension vs.
      parabolic flight.
AB  - INTRODUCTION: The effect of reducing gravity on locomotion has been studied using
      microgravity analogues. However, there is no known literature comparing
      locomotion in actual microgravity (AM) to locomotion in simulated microgravity
      (SM). METHODS: Five subjects were tested while walking at 1.34 m x s(-1) and
      running at 3.13 m x s(-1) on a treadmill during parabolic flight and on a
      microgravity simulator. The external load (EL) in AM and SM was provided by
      elastomer bungees at approximately 55% (low) and 90% (high) of the subjects'
      bodyweight (BW). Lower body joint kinematics and ground reaction forces were
      measured during each condition. Effect size and its 95% confidence interval were
      computed between gravitational conditions for each outcome variable. RESULTS: In
      AM, subjects attained approximately 15-21 degrees greater hip flexion during
      walking and 19-25 degrees greater hip flexion during running. Hip range of motion
      was greater in AM during running by approximately 12-17 degrees. Trunk motion was
      4 degrees less in SM than AM during walking. Peak impact force was greater in SM
      than in AM during walking with a low EL (SM = 0.95 +/- 0.04 BW; AM = 0.76 +/-
      0.04 BW) and contact times were greater in SM. CONCLUSIONS: Subtle differences
      exist in locomotion patterns, temporal kinematics, and peak impact ground
      reaction forces between AM and SM. The differences suggest possible adaptations
      in the motor coordination required between gravitational condition, and potential
      differences in adaptations that are dependent upon if training occurs in actual
      or simulated microgravity.

PMID- 21197854
TI  - Acceleration tolerance after ingestion of a commercial energy drink.
AB  - BACKGROUND: Caffeine ingestion has been demonstrated to increase physical
      performance in some situations. This study examined the ability of a commercial
      energy drink containing caffeine to enhance acceleration tolerance and strength
      under G load. METHODS: Eight experienced centrifuge subjects completed three
      separate experimental acceleration exposures following ingestion of 11.5 ml x kg(
      1) bodyweight of (1) a commercial energy drink, providing 5.0 mg caffeine/kg
      bodyweight; (2) a commercial energy drink without caffeine; or 3) a placebo. The
      acceleration exposures consisted of a relaxed gradual onset run to peripheral
      light loss, a rapid onset run to 6 G for 15 s, and a simulated air combat
      maneuver (SACM) run of repeated alternations between 4.5 G for 15 s and 7 G for
      15 s until volitional exhaustion. RESULTS: Relaxed G tolerance was 13% higher
      under the caffeinated energy drink session, whereas SACM duration did not differ
      among the drink conditions. Hip adductor muscle strength was 37% lower during the
      placebo session than during the other two sessions. CONCLUSION: Consumption of a
      caffeine-based energy drink may enhance relaxed G tolerance and may increase
      strength, but does not impact acceleration tolerance duration.

PMID- 21197855
TI  - Torso undergarments: their merit for clothed and armored individuals in hot-dry
      conditions.
AB  - INTRODUCTION: The aim of this study was to evaluate how the textile composition
      of torso undergarment fabrics may impact upon thermal strain, moisture transfer,
      and the thermal and clothing comfort of fully clothed, armored individuals
      working in a hot-dry environment (41.2 degrees C and 29.8% relative humidity).
      METHODS: Five undergarment configurations were assessed using eight men who
      walked for 120 min (4 km x h(-1)), then alternated running (2 min at 10 km x h(
      1)) and walking (2 min at 4 km x h(-1)) for 20 min. Trials differed only in the
      torso undergarments worn: no t-shirt (Ensemble A); 100% cotton t-shirt (Ensemble
      B); 100% woolen t-shirt (Ensemble C); synthetic t-shirt (Ensemble D: nylon,
      polyethylene, elastane); hybrid shirt (Ensemble E). RESULTS: Thermal and
      cardiovascular strain progressively increased throughout each trial, with the
      average terminal core temperature being 38.5 degrees C and heart rate peaking at
      170 bpm across all trials. However, no significant between-trial separations were
      evident for core or mean skin temperatures, or for heart rate, sweat production,
      evaporation, the within-ensemble water vapor pressures, or for thermal or
      clothing discomfort. CONCLUSION: Thus, under these conditions, neither the t
      shirt textile compositions, nor the presence or absence of an undergarment,
      offered any significant thermal, central cardiac, or comfort advantages.
      Furthermore, there was no evidence that any of these fabrics created a
      significantly drier microclimate next to the skin.

PMID- 21197856
TI  - Hypercortisolism as a potential concern for submariners.
AB  - Cortisol is a stress-response hormone that is important for survivability in
      fight or flight situations. Hypercortisolism is a state of chronically elevated
      cortisol levels due to a failure to return to, or maintain baseline levels. It is
      a condition that is often undiagnosed and can aid in the development of many
      physiological and psychological health problems. Some of the health ailments
      associated with hypercortisolism include metabolic syndrome, decreases in bone
      mineral density, and depression. Chronic stress and sleep deprivation are two
      common causes of hypercortisolism, both areas of concern within the submarine
      community. This review discusses the etiology of hypercortisolism and the
      likelihood of submariner vulnerability to the condition along with health
      problems associated with it. Lastly, strategies to prevent chronic elevation of
      cortisol and mitigate the potential health risks associated with the condition
      are covered.

PMID- 21197857
TI  - Radio speech communication problems reported in a survey of military pilots.
AB  - INTRODUCTION: Despite technological advances in conveying information, speech
      communication is still a key safety factor in aviation. Effective radio
      communication is necessary, for example, in building and maintaining good team
      situation awareness. However, little has been reported concerning the prevalence
      and nature of radio communication problems in everyday working environments in
      military aviation. METHODS: We surveyed Finnish Defense Forces pilots regarding
      the prevalence of radio speech communication problems. RESULTS: Of the 225 pilots
      contacted, 75% replied to our survey. Altogether 138 of the respondents were
      fixed-wing pilots and 31 were helicopter pilots. Problems in radio communication
      occurred, on average, during 14% of flight time. The most prevalent problems were
      multiple speakers on the same radio frequency band causing overlapping speech,
      missing acknowledgments, high background noise especially during helicopter
      operations, and technical problems. Of the respondents, 18% (31 pilots) reported
      having encountered at least one potentially dangerous event caused by problems in
      radio communication during their military aviation career. If the employer were
      to offer extra hearing protection, such as custom-made ear plugs, 93% of the
      pilots indicated that they would use it. DISCUSSION: Communication can be a
      flight safety factor especially during intense air combat exercises and other
      information-loaded flights. During these situations, communication should be
      clear and focused on the most essential information. So, training and technical
      improvements are necessary for better communication. High quality radio speech
      communication also improves operational effectiveness in military aviation.

PMID- 21197858
TI  - Clinical risk management approach for long-duration space missions.
AB  - INTRODUCTION: In the process of crewmember evaluation and certification for long
      duration orbital missions, the International Space Station (ISS) Multilateral
      Space Medicine Board (MSMB) encounters a surprisingly wide spectrum of clinical
      problems. Some of these conditions are identified within the ISS Medical
      Standards as requiring special consideration, or as falling outside the consensus
      Medical Standards promulgated for the ISS program. METHODS: To assess the
      suitability for long-duration missions on ISS for individuals with medical
      problems that fall outside of standards or are otherwise of significant concern,
      the MSMB has developed a risk matrix approach to assess the risks to the
      individual, the mission, and the program. The goal of this risk assessment is to
      provide a more objective, evidence- and risk-based approach for aeromedical
      disposition. Using a 4 x 4 risk matrix, the probability of an event is plotted
      against the potential impact. Event probability is derived from a detailed review
      of clinical and aerospace literature, and based on the best available evidence.
      The event impact (consequences) is assessed and assigned within the matrix.
      RESULTS: The result has been a refinement of MSMB case assessment based on
      evidence-based data incorporated into a risk stratification process. This has
      encouraged an objective assessment of risk and, in some cases, has resulted in
      recertification of crewmembers with medical conditions which hitherto would
      likely have been disqualifying. CONCLUSIONS: This paper describes a risk matrix
      approach developed for MSMB disposition decisions. Such an approach promotes
      objective, evidence-based decision-making and is broadly applicable within the
      aerospace medicine community.

PMID- 21197859
TI  - Arterial gas embolism during pressure tolerance testing in a hyperbaric chamber:
      a report of two cases.
AB  - This is a report of two cases of arterial gas embolism (AGE) occurring during the
      course of routine pressure tolerance testing (PTT) of Canadian Forces divers in a
      dry hyperbaric chamber. PTT is used by many military organizations as a means to
      determine whether divers can sustain a hyperbaric challenge similar to that to
      which they will be exposed during their diving duties. Problems arising from such
      testing are usually limited to issues of equalization and minor otic barotraumas.
      Incidents of AGE resulting from hyperbaric chamber exposures in general are very
      unusual. The incidents reported here are the first such cases arising in military
      divers during PTT to be reported in the extant literature. In one case a
      potential precipitating pulmonary lesion was identified during post-event chest
      imaging. In the other case, while presenting with all the usual hallmarks of an
      AGE, no predisposing pulmonary lesion was identified. Ascent rates were within
      the limits considered acceptable by the Canadian Forces for PTT. The cases are
      useful in examining the pathophysiologic mechanisms underlying pulmonary
      barotrauma and AGE, and raise questions as to the appropriate screening
      procedures for military divers in this regard.

PMID- 21197860
TI  - Brain bucket MRI.

PMID- 21197861
TI  - You're the flight surgeon. Wolfe-Parkinson-White pattern.

PMID- 21197863
TI  - Space exploration.

PMID- 21197862
TI  - This month in aerospace medicine history.

PMID- 21197865
TI  - Gifts.

PMID- 21197864
TI  - The Undersea and Space Medicine Research Lab at Dartmouth.

PMID- 21197866
TI  - Complications with a domino effect.

PMID- 21197867
TI  - Representing medicine in courtroom. The Litigation Center of the American Medical
      Association and the State Medical Societies.

PMID- 21197868
TI  - Using reminder/recall to improve immunization rates in Arkansas.

PMID- 21197869
TI  - Squamous cell lung cancer presenting with pulmonary lymphangitic carcinomatosis.
AB  - Pulmonary lymphangitic carcinomatosis (PLC) refers to the infiltration of lung
      lymphatic channels with metastatic carcinoma and is associated with a dismal
      prognosis. PLC accompanies circa 7% of all pulmonary metastases and is most
      commonly caused by various metastatic adenocarcinomas. Only two cases of PLC due
      to squamous cell lung carcinoma have been reported to date in the English
      literature. We report herein a unique case of squamous cell lung carcinoma with
      lymphangitic spread, displaying bilateral and diffuse bronchial tree involvement
      that might have been a result of invasion from the pulmonary lymphatics into the
      bronchial lumen.

PMID- 21197870
TI  - Injury prevention: role of the hospital-based Child Passenger Safety Program
      (CPSP).
AB  - Motor vehicle crashes (MVC) are the leading cause of death for people 3 to 34
      years of age. Despite evidence that child safety seats (CSS) reduce the risk of
      fatal injury by 71% for infants (< 1 year of age) and by 54% for toddlers (1-4
      years of age) in passenger cars, 48% of the 23 Arkansas children under age 16
      that died in 2007 were unrestrained. We review the goals of a hospital-based
      CPSP, briefly review one American Academy of Pediatrics (AAP) Policy Statement,
      describe how one CPSP functions, and provide resources to those interested in
      program development.

PMID- 21197871
TI  - Searching for relevance in a sea of CME.

PMID- 21197872
TI  - School is a great place for primary care.

PMID- 21197873
TI  - Grand rounds' growing pains.

PMID- 21197874
TI  - Learning styles.

PMID- 21197875
TI  - Credit for change.

PMID- 21197876
TI  - Healing the profession.

PMID- 21197877
TI  - Expert urges doctors to test ACO model.

PMID- 21197878
TI  - Test anxiety.

PMID- 21197879
TI  - CME ASAP.

PMID- 21197880
TI  - Linking medical education and patient care.

PMID- 21197881
TI  - Reshaping physician education.

PMID- 21197882
TI  - Is the CME system obsolete?
AB  - Changes in medical practice and a greater emphasis on lifelong learning are
      prompting a closer look at the efficacy of continuing medical education (CME).
      This article outlines the shortcomings of the current CME system, describes
      findings from two recent reports about its status, and presents recommendations
      for a new system to make continuing education more relevant to medical practice.

PMID- 21197883
TI  - Engaging physicians in CME: the power of theater.
AB  - HealthPartners Institute for Medical Education has developed an innovative
      continuing medical education model that uses elements of theater to explore
      complex issues in health care and increase participant engagement. The model was
      recently used during a hospital medicine retreat. The learning event included a
      four-part monologue in which an actor portrayed a patient, interactive didactic
      sessions, a game show titled "Who Wants to be Hospitalized a MillionTimes,"
      computerized simulations, and a call for clinicians to help patients adopt
      healthier behaviors. Post-event evaluations demonstrated that participants gained
      valuable clinical knowledge and appreciated the combination of active learning
      and theater.

PMID- 21197884
TI  - Impact of new duty-hour rules on residency training.
AB  - On the surface, changing the rules related to the number of hours residents work
      per day and per week sounds like a good idea. Theoretically, residents who work
      fewer hours would be less tired and provide better patient care. But even small
      changes in residency training programs have implications for the quality of the
      educational experience and the cost of training, as well as patient care. This
      article highlights the challenges that two Minnesota residency programs are
      facing as they adapt to the new rules around residents' work hours.

PMID- 21197886
TI  - Pledges on dementia care.

PMID- 21197885
TI  - Preventing elective induction before 39 weeks.
AB  - Induction of labor has become a common practice in Minnesota and elsewhere in the
      United States during the last three decades. Yet a review of the research shows
      that elective induction has no medical benefit and, in fact, is associated with
      risks to both the mother and infant, particularly if labor is induced before 39
      weeks gestation. This article reports the recommendations of a Minnesota
      Department of Human Services advisory group on perinatal practices and labor
      induction. The recommendations include having hospitals establish new policies on
      elective induction and encouraging medical providers to educate patients about
      the risks of early-term induction.

PMID- 21197887
TI  - Alliance will collaborate on improving dementia care.

PMID- 21197888
TI  - Looking for a new direction.

PMID- 21197889
TI  - Breast cancer aware.

PMID- 21197890
TI  - Improving care.

PMID- 21197891
TI  - Doing time: health care in the criminal justice system.
AB  - Prisoners over the age of 60 are the fastest growing age group in prison, but
      they face isolation and discrimination because their specialist health, social
      and resettlement needs are not being met. This article explores the problems
      faced by this group and highlights examples of good practice.

PMID- 21197892
TI  - Promoting skin health in older people.
AB  - This article examines general skin care for older people, including barrier
      function and changes associated with the ageing process. A systematic approach to
      skin assessment is also provided and general skin care with a focus on personal
      hygiene is discussed. Methods by which older people themselves and nursing staff
      can help to promote and improve skin health are identified.

PMID- 21197893
TI  - A training course that empowers hard-to-reach carers.
AB  - Run by first aid charity St John Ambulance, an innovative project pioneered in
      Dorset is offering nurses' expertise to carers who often feel isolated and
      desperate.

PMID- 21197894
TI  - Reflection on life experience as an aid to deeper learning.
AB  - This article examines the rationale for a four-week life experience placement for
      nursing students developed at the school of community and health sciences at
      London's City University. The authors describe how students' perceptions of old
      age have been challenged by listening to someone's life history and observing
      older people in groups and in the community. Student Daniel Fitzpatrick reflects
      on his experience of undertaking the placement in relation to his own feelings
      and expectations of old age.

PMID- 21197895
TI  - Preventive action.

PMID- 21197896
TI  - Deadline ICD-10 Y2K all over again? There are five critical areas to address when
      planning the shift to ICD-10.

PMID- 21197897
TI  - Botsford's big bang. A Michigan hospital counts down the days to its EMR system
      launch and readies for meaningful use.

PMID- 21197898
TI  - A new prescription for building trust online. Only four out of 100 adults access
      healthcare services online. Here's how to reach the other 96 percent.

PMID- 21197899
TI  - Identifying and dealing with drug diversion. How hospitals can stay one step
      ahead.

PMID- 21197900
TI  - Keys to understanding EHR adoption. Jumping into EHR technology too early may be
      painful and costly, but standing on the sidelines could be devastating.

PMID- 21197901
TI  - How to plan for the new era of data management. The transitions to HIPAA EDI
      version 5010 and ICD-10 will only further complicate electronic data gathering,
      reporting and security.

PMID- 21197902
TI  - Navigating ICD-10: how to get from point A to point B. Preparing for ICD-10 and
      5010 in tandem gives one health plan a roadmap to meet state requirements and
      enhance operations.

PMID- 21197903
TI  - The perfect healthcare storm. U.S. EHR effort poised to falter unless course
      change comes soon.

PMID- 21197904
TI  - Joint Commission annual report shows big improvements for hospital care.

PMID- 21197905
TI  - Joint Commission Center for Transforming Healthcare announces second set of
      solutions.

PMID- 21197906
TI  - Clarification: CMS will accept Alternatives to manufacturer's maintenance
      recommendations.

PMID- 21197907
TI  - Updated sentinel event statistics for midyear 2010.

PMID- 21197908
TI  - Joint commission plans for implementation of MDS 3.0 for long term care.

PMID- 21197909
TI  - Approved: Policy regarding accreditation status of organizations that cease
      provision of services for a period of time.

PMID- 21197910
TI  - Governor looks forward to leading AHCA/NCAL.

PMID- 21197911
TI  - Choices & teamwork improve end-of-life care.

PMID- 21197912
TI  - Engage every customer. Great customer service requires consistency.

PMID- 21197913
TI  - Dementia: spotlight on abilities.

PMID- 21197914
TI  - Don't forget the exclusion lists.

PMID- 21197915
TI  - Importance of terms and concepts in science and in life.

PMID- 21197916
TI  - Integrating evidence-based practice with educational theory in clinical practice
      for nurse practitioners: bridging the theory practice gap.

PMID- 21197917
TI  - Improving glycemic control in older adults using a videophone motivational
      diabetes self-management intervention.
AB  - Older adults experience the greatest burden of diabetes. Resources must be
      available and accessible to empower older adults to perform diabetes self-care.
      The purpose of this study was to evaluate a videophone motivational interviewing
      (MI) diabetes self-management education (DSME) intervention to improve glycemic
      control of rural older adults. Sixty-six participants (mean age = 64.9 years,
      range 60-81) with uncontrolled diabetes were enrolled in a 6-month videophone
      intervention. Experimental group participants (n = 34) received weekly, then
      monthly, videophone MI DSME calls, whereas control participants (n = 32) received
      monthly videophone healthy-lifestyle education calls. Although both groups
      experienced a decreased HbA1c, there was a statistically significant difference
      in experimental group mean values (p = .015), but not the control group (p =
      .086). The experimental group demonstrated statistically significant increases in
      diabetes knowledge (p = .023) and diabetes self-efficacy (p = .002). Experimental
      group participants with high self-efficacy in contrast to low self-efficacy had a
      statistically significant decrease in HbA1c (p = .043).

PMID- 21197918
TI  - Issues in cross-cultural comparative research.
AB  - It is the purpose of this article to describe the methodological issues when
      designing qualitative cultural comparative studies, which may be used to address
      health disparities. Overall, two broad types of comparative studies were found:
      primary and secondary comparative studies. Methodological issues to consider when
      designing primary studies were reviewed. The main areas discussed in this article
      relate to sampling and study purpose, sample boundaries, theoretical context,
      concept development, analogous comparisons, and systematic comparisons. Nurses
      are in a prime position to pose the qualitative research questions needed to
      address health disparities within their clinical settings. It is suggested that
      awareness of the method types and issues might inspire further qualitative
      comparative work.

PMID- 21197919
TI  - Quality of life model: predictors of quality of life among sick older adults.
AB  - The aim of this study was to explore how depressive symptoms, physical function,
      health satisfaction, age, and environmental conditions predict quality of life
      (QoL) in a conceptual model based on the Wilson and Cleary's Model (WCM). A
      stratified sample by age, gender, and living area was drawn from the Norwegian
      population of older adults receiving community health care (mean age of 78.6
      years, 94.4% living at home, 5.6% living in nursing homes). The study is part of
      a larger international study. Face-to-face interviews were conducted using the
      WHOQoL-Old, the WHOQoL-Bref Environment domain, the Geriatric Depression Scale,
      the Short Form SF-12, and sociodemographic and health questions. A path analysis
      (structural equation modeling) showed that the overall model provided empirical
      evidence for linkages in the WCM. QoL was manifested by significant direct
      effects of environmental conditions and health satisfaction. In addition,
      environmental conditions had indirect effects on QoL, in particular via
      depressive symptoms and health satisfaction. This model may help nurses in
      community health care to collect and assess information, to suggest suitable
      interventions, and to guide decision making.

PMID- 21197920
TI  - Knowledge, attitudes, and perceptions of advanced practice nurses regarding
      urinary incontinence in older adult women.
AB  - This study examined the level of knowledge and the attitudes and perceptions of
      advanced practice nurses (APNs) regarding urinary incontinence (UI) in older
      adult women. UI is a common health issue for older adult women, and APNs are in a
      unique position as health care providers to prevent, diagnose, treat, and manage
      the condition successfully. Little is known about how well APNs were educated
      regarding UI, especially in older adult women. Purposive sampling was utilized to
      conduct a cross-sectional, descriptive, and correlational design study. Fifty
      four APNs completed a questionnaire developed by the author based on the aging
      literature, advanced practice nursing competencies, and UI guidelines. Findings
      suggest that APNs generally have positive attitudes, perceptions, and knowledge
      of UI in women. However, participants had difficulty in applying this knowledge
      to the clinical setting: assessing, diagnosing, treating, and managing UI. More
      emphasis is needed in graduate nursing curriculums and in precepted clinical
      experiences regarding UI in women.

PMID- 21197921
TI  - Patient's page. Meth mouth.

PMID- 21197922
TI  - Meth mouth: a modern epidemic.

PMID- 21197923
TI  - ADA applauds legislators for 'meth mouth' bills.

PMID- 21197924
TI  - Meth mouth & teeth.

PMID- 21197925
TI  - "Meth mouth" for the general practitioner.

PMID- 21197926
TI  - The use of the Zung Self-Rating Depression Scale to assist in the case management
      of patients living with HIV/AIDS.
AB  - Depression is a common comorbidity in people with HIV/AIDS, frequently impacting
      disease status by direct effects on immune fuinction and adherence to
      antiretroviral treatment. For case managers, who are often the main contacts for
      patients, quick and simple identification of patients at high risk for depression
      can be both a challenge and a priority. These patients should be screened at the
      primary point of care and then referred to mental health providers for further
      evaluation or diagnosis. Here we report the experiences in three diverse case
      management settings using the Zung Self-Rating Depression Scale for patient self
      reporting of depression symptoms. The three clinics--Broward House in Wilton
      Manors, Florida; BIENESTAR Human Services in Los Angeles, California, and the
      West Midtown Medical Group in New York City--serve diverse racial and ethnic
      populations with substantial HIV infection rates in urban and rural communities.
      Benefits of using this validated tool include increased patient self-awareness
      and acceptance by mental health providers, thereby facilitating a final diagnosis
      that leads to improved implementation of treatment for depression. Case
      management settings provide a unique point of contact to unite clients with
      mental health care, especially in disease settings where depression or other
      mental health conditions are prevalent.

PMID- 21197927
TI  - Do sequential chest radiographs prompt changes in therapy for home mechanical
      ventilation children admitted for pneumonia?
AB  - How many chest radiographs prompt changes in therapy for home mechanical
      ventilation (HMV) patients admitted to the hospital for pneumonia? Since HMV
      patients are more complex than those with simple community-acquired pneumonia, it
      is not known how many chest radiographs are needed for optimal management. To
      answer this, we reviewed all HMV patients admitted for pneumonia from July 2007
      through June 2008. Demographic data, sequential chest radiographs, and changes in
      respiratory orders within 24 hours were recorded Childrens Hospital Los Angeles
      followed 180 HMV patients. Twenty-eight patients (16%) were admitted (36
      readmissions). Twenty-five of these patients (90%) required full-time HMV
      Eighteen patients (64%) had the diagnosis of chronic lung disease. On discharge,
      24 patients (66%) had residual pneumonia on chest radiographs. We conclude that
      HMV patients averaged five chest radiographs per pneumonia admission. Two-thirds
      of the chest radiographs did not prompt subsequent changes in respiratory
      therapy. More than one-third of the chest radiographs found no interval changes.
      The majority of discharges were not contingent on resolution of the chest
      radiographs findings. We speculate that the frequency of chest radiographs could
      be less and that chest radiographs were not the sole predictors of changes in
      respiratory treatment or the decision to discharge.

PMID- 21197929
TI  - New York City Department for the Aging annual plan summary 2010-2011, part 2.

PMID- 21197928
TI  - Sweeping changes to New York's powers of attorney.

PMID- 21197930
TI  - Sunset years in sunny Florida: experiences of homelessness among the elderly.

PMID- 21197931
TI  - Health care technology, health care rationing, and older Americans: enough
      already!

PMID- 21197932
TI  - Role of the management pathway in the care of advanced COPD patients in their own
      homes.
AB  - Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and
      mortality worldwide, and the incidence and prevalence are rising every decade.
      The cost of hospital admission is substantial and is the single largest source of
      expenditure in care of COPD patients. Home-based intervention has been shown to
      provide long-term cost benefit in a range of chronic illnesses; however, the role
      of home visits by respiratory therapists (RT) in COPD management has not been
      evaluated. The aim of this study was to assess the efectiveness of a management
      pathway in the care of oxygen-dependent COPD patients in their homes. Oxygen
      dependent COPD patients were enrolled in the management pathway after discharge
      from the hospital or referred from a provider's office. At least three home
      visits were made: the first within 3 days of enrollment; the second in 1 month,
      and the third 10 months later. Three hundred and twenty-four patients were
      enrolled in the study. During the study period the overall hospitalization rate
      dropped (11% per month at the second visit vs. 2.1% per month at the third
      visit). The patients' understanding of the disease improved substantially (21.6%
      vs. 83.9%), knowledge of medications the patients were taking improved (56.0% vs.
      87.0%), and appropriate use of medications increased (52.0% vs. 86.0%). In our
      community, this RT-led program helped patients' self-management of COPD in their
      own homes by increasing understanding of the disease, assisted physicians in
      monitoring their patients, and reduced hospitalization.

PMID- 21197933
TI  - Who said 75 is old?

PMID- 21197934
TI  - Doctor-patient partnership: patients of advanced age use medical diaries to
      improve coordination of care.

PMID- 21197935
TI  - Ceramics.

PMID- 21197936
TI  - Ceramics: rationale for material selection.
AB  - All imaginable types of materials and techniques, from very conservative ceramic
      restorations to very complex restorations of either metal or high-strength
      crystalline ceramics veneered with porcelain, have been introduced and tried
      throughout the years, with varying levels of success. However, there is
      considerable misinformation and a general lack of published rational treatment
      planning guidelines about when to use the ceramics available in dentistry. This
      article provides a systematic process for treatment planning with ceramic
      materials. Specific guidelines are outlined for the appropriate clinical
      conditions for using the various ceramic materials.

PMID- 21197937
TI  - Ceramics overview: classification by microstructure and processing methods.
AB  - The plethora of ceramic systems available today for all types of indirect
      restorations can be confusing--and overwhelming--for the clinician. Having a
      better understanding of them is key. The authors use classification systems based
      on the microstructural components of ceramics and the processing techniques to
      help illustrate the various properties and uses.

PMID- 21197938
TI  - Materials for chairside CAD/CAM restorations.
AB  - Chairside computer-aided design/computer-aided manufacturing (CAD/CAM) systems
      have become considerably more accurate, efficient, and prevalent as the
      technology has evolved in the past 25 years. The initial restorative material
      option for chairside CAD/CAM restorations was limited to ceramic blocks.
      Restorative material options have multiplied and now include esthetic ceramics,
      high-strength ceramics, and composite materials for both definitive and temporary
      restoration applications. This article will review current materials available
      for chairside CAD/CAM restorations.

PMID- 21197939
TI  - Zirconia: material background and clinical application.
AB  - Zirconia is the oxidized form of zirconium and can exist in several phases,
      depending on the temperature. In dental ceramics, zirconia can inhibit crack
      growth and prevent catastrophic failure. The following case report demonstrates
      the use of zirconia as a framework material. Overall, zirconia has proven to be a
      strong and reliable framework material. In combination with CAD/CAM, this
      material allows for the fabrication of esthetic all-ceramic restorations in all
      areas of the mouth.

PMID- 21197941
TI  - Rethinking the dental handpiece.

PMID- 21197940
TI  - Lithium disilicate: the restorative material of multiple options.
AB  - As dentistry continues to evolve, new technologies and materials are continually
      being offered to the dental profession. Throughout the years restorative trends
      and techniques have come and gone. Some material developments have transformed
      the face of esthetic dentistry, while other initial concepts have already phased
      out and disappeared. Today, all-ceramic restorations continue to grow in the area
      of restorative dentistry, from pressed-ceramic techniques and materials to the
      growing use of zirconia, and new materials that can be created from CAD/CAM
      technology. This article will explore new uses for the all-ceramic material known
      as lithium disilicate, and the use of a digital format to design and process this
      material in new and exciting ways. An overview of the material as well as unique
      clinical procedures will be presented.

PMID- 21197942
TI  - Concern over Medicaid reinstatement.

PMID- 21197943
TI  - A national clinical licensure exam.

PMID- 21197944
TI  - Medicaid's electronic health record incentive payment program.

PMID- 21197945
TI  - Good news about ADA publications.

PMID- 21197946
TI  - Dealing with a claim of retaliation.

PMID- 21197947
TI  - Why 'I'm sorry' legislation makes so much sense.

PMID- 21197948
TI  - MDA insurance rate increase reflects the current market.

PMID- 21197949
TI  - How to master information overload.

PMID- 21197950
TI  - 30 ways to maximize your membership.

PMID- 21197951
TI  - Dr. Jerel N. Owens: dentist with a mission. Interview by Franziska Schoenfeld.

PMID- 21197952
TI  - Oral pathology quiz #23. Verruciform xanthoma.

PMID- 21197953
TI  - Studies leading to the development of a single-electron transfer (SET)
      photochemical strategy for syntheses of macrocyclic polyethers, polythioethers,
      and polyamides.
AB  - Organic photochemists began to recognize in the 1970s that a new mechanistic
      pathway involving excited-state single-electron transfer (SET) could be used to
      drive unique photochemical reactions. Arnold's seminal studies demonstrated that
      SET photochemical reactions proceed by way of ion radical intermediates, the
      properties of which govern the nature of the ensuing reaction pathways. Thus, in
      contrast to classical photochemical reactions, SET-promoted excited-state
      processes are controlled by the nature and rates of secondary reactions of
      intermediate ion radicals. In this Account, we discuss our work in harnessing SET
      pathways for photochemical synthesis, focusing on the successful production of
      macrocyclic polyethers, polythioethers, and polyamides. One major thrust of our
      studies in SET photochemistry has been to develop new, efficient reactions that
      can be used for the preparation of important natural and non-natural substances.
      Our efforts with alpha-silyl donor-tethered phthalimides and naphthalimides have
      led to the discovery of efficient photochemical processes in which excited-state
      SET is followed by regioselective formation of carbon-centered radicals. The
      radical formation takes place through nucleophile-assisted desilylation of
      intermediate alpha-silyl-substituted ether-, thioether-, amine-, and amide
      centered cation radicals. Early laser flash photolysis studies demonstrated that
      the rates of methanol- and water-promoted bimolecular desilylations of cation
      radicals (derived from alpha-silyl electron donors) exceeded the rates of other
      cation radical alpha-fragmentation processes, such as alpha-deprotonation. In
      addition, mechanistic analyses of a variety of SET-promoted photocyclization
      reactions of alpha-silyl polydonor-linked phthalimides and naphthalimides showed
      that the chemical and quantum efficiencies of the processes are highly dependent
      on the lengths and types of the chains connecting the imide acceptor and alpha
      silyl electron donor centers. We also observed that reaction efficiencies are
      controlled by the rates of desilylation at the alpha-silyl donor cation radical
      moieties in intermediate zwitterionic biradicals that are formed by either direct
      excited-state intramolecular SET or by SET between the donor sites in the
      intervening chains. It is important to note that knowledge about how these
      factors govern product yields, regiochemical selectivities, and quantum
      efficiencies was crucial for the design of synthetically useful photochemical
      reactions of linked polydonor-acceptor substrates. The fruits of these insights
      are exemplified by synthetic applications in the concise preparation of cyclic
      peptide mimics, crown ethers and their lariat- and bis-analogs, and substances
      that serve as fluorescence sensors for important heavy metal cations.

PMID- 21197955
TI  - Indocyanine green-containing nanostructure as near infrared dual-functional
      targeting probes for optical imaging and photothermal therapy.
AB  - Indocyanine green (ICG) is a near-infrared (NIR) imaging agent and is also an
      ideal light absorber for laser-mediated photothermal therapy. This NIR dye could
      serve as a basis of a dual-functional probe with integrated optical imaging and
      photothermal therapy capabilities. However, applications of ICG remain limited by
      its concentration-dependent aggregation, poor aqueous stability, nonspecific
      binding to proteins and lack of target specificity. To overcome these
      limitations, a novel ICG-containing nanostructure is designed utilizing the
      noncovalent self-assembly chemistry between phospholipid-polyethylene glycol (PL
      PEG) and ICG. The interactions between both amphiphilic ICG and PL-PEG were
      studied using absorption and fluorescence spectroscopy. The properties of ICG-PL
      PEG nanoprobe, such as absorption and fluorescence spectra, stability, morphology
      and size distribution, were also investigated. Two representative targeting
      molecules, namely, a small molecule, folic acid (FA), and a large protein,
      integrin alpha(v)beta3 monoclonal antibody (mAb), were conjugated to the surface
      of ICG-PL-PEG nanoprobe, displaying the diversity of ligand conjugation. The
      target specificity was confirmed using three cell lines with different levels of
      available folate receptors (FRs) or integrin alpha(v)beta3 expression via laser
      scanning confocal microscope and flow cytometry. This targeting ICG-PL-PEG
      nanoprobe could be internalized into targeted cells via ligand-receptor mediated
      endocytosis pathway. Our in vitro experiments showed that internalized ICG-PL-PEG
      could be used for cell imaging and selective photothermal cell destruction. These
      results represent the first demonstration of the dual functionality of ICG
      containing nanostructure for targeted optical imaging and photothermal therapy of
      cancerous cells. This novel ICG-PL-PEG nanostructure, when conjugated with other
      therapeutic and imaging agents, could become a multifunctional probe for cancer
      diagnosis and treatment.

PMID- 21197954
TI  - Methylthioinosine phosphorylase from Pseudomonas aeruginosa. Structure and
      annotation of a novel enzyme in quorum sensing.
AB  - The PA3004 gene of Pseudomonas aeruginosa PAO1 was originally annotated as a 5'
      methylthioadenosine phosphorylase (MTAP). However, the PA3004 encoded protein
      uses 5'-methylthioinosine (MTI) as a preferred substrate and represents the only
      known example of a specific MTI phosphorylase (MTIP). MTIP does not utilize 5'
      methylthioadenosine (MTA). Inosine is a weak substrate with a k(cat)/K(m) value
      290-fold less than MTI and is the second best substrate identified. The crystal
      structure of P. aeruginosa MTIP (PaMTIP) in complex with hypoxanthine was
      determined to 2.8 A resolution and revealed a 3-fold symmetric homotrimer. The
      methylthioribose and phosphate binding regions of PaMTIP are similar to MTAPs,
      and the purine binding region is similar to that of purine nucleoside
      phosphorylases (PNPs). The catabolism of MTA in P. aeruginosa involves
      deamination to MTI and phosphorolysis to hypoxanthine (MTA -> MTI ->
      hypoxanthine). This pathway also exists in Plasmodium falciparum, where the
      purine nucleoside phosphorylase (PfPNP) acts on both inosine and MTI. Three tight
      binding transition state analogue inhibitors of PaMTIP are identified with
      dissociation constants in the picomolar range. Inhibitor specificity suggests an
      early dissociative transition state for PaMTIP. Quorum sensing molecules are
      associated with MTA metabolism in bacterial pathogens suggesting PaMTIP as a
      potential therapeutic target.

PMID- 21197956
TI  - Biosafety assessment of human mesenchymal stem cells engineered by hybrid
      baculovirus vectors.
AB  - Mesenchymal stem cells (MSCs) hold promise for cell therapy, and implantation of
      MSCs engineered with a baculovirus transiently expressing the growth factor can
      augment the bone repair. To prolong the baculovirus-mediated transgene
      expression, we developed hybrid baculovirus vectors exploiting the FLP/Frt
      mediated recombination for circular episome formation. Transduction of human MSCs
      with the hybrid baculovirus vectors harboring the osteoinductive bmp2 gene
      substantially extended the BMP2 expression and improved the cellular osteogenic
      differentiation. To confirm the potential in the clinical setting, the present
      study evaluated the biosafety profile of human MSCs engineered by the hybrid
      vectors. We unraveled that transduction of MSCs with the hybrid baculovirus
      vectors slightly impeded the cell proliferation after transduction, probably due
      to the perturbation of cellular gene expression and induction of innate
      responses. Nonetheless, the hybrid baculovirus vectors did not compromise the
      cell viability and cellular differentiation. No transgene integration into the
      host chromosome and disruption of the karyotype of the MSCs were observed.
      Additionally, no upregulation of proto-oncogenes or downregulation of tumor
      suppressor genes occurred in the MSCs transduced with the hybrid baculovirus
      vectors. Neither did the transduced MSCs induce tumor formation in nude mice.
      This study not only supported the safety of MSCs for cell therapy but also
      implicated the potential of the human MSCs engineered by the hybrid baculovirus
      vectors for their applications in clinical scenarios necessitating sustained
      transgene expression.

PMID- 21197957
TI  - Mechanism of Vibrio cholerae autoinducer-1 biosynthesis.
AB  - Vibrio cholerae, the causative agent of the disease cholera, uses a cell to cell
      communication process called quorum sensing to control biofilm formation and
      virulence factor production. The major V. cholerae quorum-sensing signal CAI-1
      has been identified as (S)-3-hydroxytridecan-4-one, and the CqsA protein is
      required for CAI-1 production. However, the biosynthetic route to CAI-1 remains
      unclear. Here we report that (S)-adenosylmethionine (SAM) is one of the two
      biosynthetic substrates for CqsA. CqsA couples SAM and decanoyl-coenzyme A to
      produce a previously unknown but potent quorum-sensing molecule, 3-aminotridec-2
      en-4-one (Ea-CAI-1). The CqsA mechanism is unique; it combines two enzymatic
      transformations, a beta,gamma-elimination of SAM and an acyltransferase reaction
      into a single PLP-dependent catalytic process. Ea-CAI-1 is subsequently converted
      to CAI-1, presumably through the intermediate tridecane-3,4-dione (DK-CAI-1). We
      propose that the Ea-CAI-1 to DK-CAI-1 conversion occurs spontaneously, and we
      identify the enzyme responsible for the subsequent step: conversion of DK-CAI-1
      into CAI-1. SAM is the substrate for the synthesis of at least three different
      classes of quorum-sensing signal molecules, indicating that bacteria have evolved
      a strategy to leverage an abundant substrate for multiple signaling purposes.

PMID- 21197958
TI  - Online mass spectrometric analysis of proteins/peptides following electrolytic
      cleavage of disulfide bonds.
AB  - The disulfide bond bridge is an important post-translational modification for
      proteins. This study presents a structural analysis of biologically active
      peptides and proteins containing disulfide bonds using electrochemistry (EC)
      online combined with desorption electrospray ionization mass spectrometry (DESI
      MS), in which the sample undergoes electrolytic disulfide cleavage in an
      electrochemical flow cell followed by MS detection. Using this EC/DESI-MS method,
      the disulfide-containing peptides can be quickly identified from enzymatic
      digestion mixtures, simply based on the abrupt decrease in their relative ion
      abundances after electrolysis. Peptide mass mapping and tandem MS analysis of the
      ions of the resulting free peptide chains can possibly establish the disulfide
      linkage pattern and sequence the precursor peptides. In this regard, the method
      provides much more chemical information than previous analogous electrochemical
      analyses. In addition, derivatization of thiols by selective selenamide reagents
      is useful for easy recognition of reduced peptide ions and the number of their
      free thiols. Furthermore, electrolytic reduction of proteins (e.g., alpha
      lactalbumin) leads to increased charges on the detected protein ions, revealing
      the role of disulfide bonds on maintaining protein conformation. This
      electrochemical mass spectrometric method is fast (completed in few minutes) and
      does not need chemical reductants, potentially having valuable applications in
      proteomics research.

PMID- 21197959
TI  - The cyanobacteriochrome, TePixJ, isomerizes its own chromophore by converting
      phycocyanobilin to phycoviolobilin.
AB  - The cyanobacterial phototaxis regulator protein, TePixJ, is a member of the
      subfamily of cyanobacteriochromes that binds phycoviolobilin (PVB) as a
      chromophore and exhibits reversible photoconversion between blue light-absorbing
      (Pb) and green light-absorbing (Pg) forms. We reconstituted the PVB-binding
      photoactive holocomplex in vivo and in vitro. Coexpression of the apoprotein and
      phycocyanobilin (PCB) in Escherichia coli (in vivo reconstitution) produced a
      mixture of the PCB-bound and PVB-bound holoproteins. Reconstitution in vitro of
      the apoprotein and synthetic PCB quickly generated a photoactive complex, which
      covalently bound PCB and exhibited partially reversible photoconversion between
      two species by UV-vis spectroscopy (with a lambda(max) values of 430 and 545 nm).
      Further incubation produced slow isomerization of PCB to PVB with concomitant
      improvement of photoreactivity. Site-directed mutagenesis confirmed that Cys522,
      and a second conserved Cys (Cys494), are both essential for the assembly of the
      photoactive complex. Fourier transform infrared (FTIR) spectroscopy revealed
      green light-induced cross-linking, and blue light-induced release, of a thiol
      group, possibly that of Cys494. These results suggest that the Pb/Pg-type
      cyanobacteriochrome TePixJ is assembled in at least three steps: (i) rapid and
      stable chromophorylation of PCB, (ii) additional photoreversible
      chromophorylation, and (iii) subsequent slow isomerization of PCB to PVB. In
      addition to its known autolyase activity with Cys522 and photoreversible
      isomerase activity (of the Z and E isomers at C15 and C16 of PCB), the GAF domain
      of TePixJ therefore appears to have other roles: as an isomerase (converting PCB
      to PVB) and as a photoreversible autolyase with a second conserved Cys residue.

PMID- 21197960
TI  - Intracellular trafficking and subcellular distribution of a large array of HPMA
      copolymers.
AB  - The basic physicochemical properties that determine the distribution and fate of
      synthetic macromolecules in living cells were characterized using fluorescently
      labeled HPMA (N-(2-hydroxypropyl)methacrylamide) copolymers. Twelve different
      classes of water-soluble copolymers were created by incorporating eight different
      functionalized comonomers. These comonomers possessed functional groups with
      positive or negative charges or contained short hydrophobic peptides. The
      copolymers were fractionated to create parallel "ladders" consisting of 10
      fractions of narrow polydispersity with molecular weights ranging from 10 to 200
      kDa. The intracellular distributions were characterized for copolymer solutions
      microinjected into the cytoplasm of cultured ovarian carcinoma cells. Even the
      highest molecular weight HPMA copolymers were shown to quickly and evenly diffuse
      throughout the cytoplasm and remain excluded from membrane-bound organelles,
      regardless of composition. The exceptions were the strongly cationic copolymers,
      which demonstrated a pronounced localization to microtubules. For all copolymers,
      nuclear entry was consistent with passive transport through the nuclear pore
      complex (NPC). Nuclear uptake was shown to be largely dictated by the molecular
      weight of the copolymers, however, detailed kinetic analyses showed that nuclear
      import rates were moderately, but significantly, affected by differences in
      comonomer composition. HPMA copolymers containing amide-terminated phenylalanine
      glycine (FG) sequences, analogous to those found in the NPC channel protein,
      demonstrated a potential to regulate import to the nuclear compartment. Kinetic
      analyses showed that 15 kDa copolymers containing GGFG, but not those containing
      GGLFG, peptide pendant groups altered the size-exclusion characteristics of NPC
      mediated nuclear import.

PMID- 21197961
TI  - Encapsulation of bacterial cells in electrospun microtubes.
AB  - Encapsulation of whole microbial cells in microtubes for use in bioremediation of
      pollutants in water systems was the main focus of this investigation.
      Coelectrospinning of a core polymeric solution with bacterial cells and a shell
      polymer solution using a spinneret with two coaxial capillaries resulted in
      microtubes with porous walls. The ability of the microtube's structure to support
      cell attachment and maintain enzymatic activity and proliferation of the
      encapsulated microbial cells was examined. The results obtained show that the
      encapsulated cells maintain some of their phosphatase, beta-galactosidase and
      denirification activity and are able to respond to conditions that induce these
      activities. This study demonstrates electrospun microtubes are a suitable
      platform for the immobilization of intact microbial cells.

PMID- 21197962
TI  - Adsorption behavior and adhesive properties of biopolyelectrolyte multilayers
      formed from cationic and anionic starch.
AB  - Cationic starch (D.S. 0.065) and anionic starch (D.S. 0.037) were used to form
      biopolyelectrolyte multilayers. The influence of the solution concentration of
      NaCl on the adsorption of starch onto silicon oxide substrates and on the
      formation of multilayers was investigated using stagnation point adsorption
      reflectometry (SPAR) and quartz crystal microbalance with dissipation (QCM-D).
      The wet adhesive properties of the starch multilayers were examined by measuring
      pull-off forces with the AFM colloidal probe technique. It was shown that
      polyelectrolyte multilayers (PEM) can be successfully constructed from cationic
      starch and anionic starch at electrolyte concentrations of 1 mM NaCl and 10 mM
      NaCl. The water content of the PEMs was approximately 80% at both electrolyte
      concentrations. However, the thickness of the PEMs formed at 10 mM NaCl was
      approximately twice the thickness formed at 1 mM NaCl. The viscoelastic
      properties of the starch PEMs, modeled as Voigt elements, were dependent on the
      polyelectrolyte that was adsorbed in the outermost layer. The PEMs appeared to be
      more rigid when capped by anionic starch than when capped by cationic starch. The
      wet adhesive pull-off forces increased with layer number and were also dependent
      on the polyelectrolyte adsorbed in the outermost layer. Thus, starch PEM
      treatment has a large potential for increasing the adhesive interaction between
      solid substrates to levels higher than can be reached by a single layer of
      cationic starch.

PMID- 21197963
TI  - Degradation properties of co-continuous calcium-phosphate-polyester composites.
AB  - Co-continuous composites consisting of a porous calcium phosphate matrix
      (hydroxyapatite, HA, or beta-tricalcium phosphate, TCP) filled with poly(D,L
      lactide) (PDLLA) were produced with two different methods: in situ polymerization
      of D,L-lactide monomer inside the matrix, or infiltration of the matrix with
      molten polymer. The influence of the calcium phosphate matrix as well as the
      manufacturing method on the degradation were investigated with accelerated in
      vitro studies at 42  degrees C in pH 7.4 phosphate-buffered saline (PBS), with
      some controls at 37  degrees C. The results show that samples produced with the
      infiltration method had higher initial molecular weights leading to a later onset
      of mass loss. Heterogenous polymer degradation was still present in the
      composites, as indicated by molecular weight distributions and glass transition
      temperature measurements. The calcium phosphate matrix delayed degradation, with
      evidence from X-ray microtomography suggesting that the polymer degrades more
      slowly in proximity to the matrix.

PMID- 21197964
TI  - Broadband spectral probing revealing ultrafast photochemical branching after
      ultraviolet excitation of the aqueous phenolate anion.
AB  - Electron photodetachment from the aromatic anion phenolate excited into the pi
      pi* singlet excited state (S(1)) in aqueous solution is studied with ultrafast
      transient absorption spectroscopy with a time resolution of better than 50 fs.
      Broad-band transient absorption spectra from 300 to 690 nm are recorded. The
      transient bands are assigned to the solvated electron, the phenoxyl radical, and
      the phenolate S(1) excited state, and confirmation of these assignments is
      achieved using both KNO(3) as electron quencher and time-resolved fluorescence to
      measure singlet excited state dynamics. The phenolate fluorescence lifetime is
      found to be short (~20 ps) in water, but the fast decay is only in part due to
      the electron ejection channel from S(1). Using global target analysis, two
      electron ejection channels are identified, and we propose that both vibrationally
      hot S(1) state and the relaxed S(1) state are direct precursors for the solvated
      electron. Therefore, electron ejection is found just to compete with picosecond
      time scale vibrational relaxation and electronic radiationless decay channels.
      This contrasts markedly with <100 fs electron detachment processes for inorganic
      anions.

PMID- 21197965
TI  - Octanol-triggered self-assemblies of the CTAB/KBr system: a microstructural
      study.
AB  - A micelle-vesicle transition induced by n-octanol C(8)OH was observed in an
      aqueous cetyltrimethylammonium bromide (CTAB)/potassium bromide (KBr) system.
      This transition was investigated by viscosity, rheology, dynamic light scattering
      (DLS), and direct imaging technique, cryo-transmission electron microscopy (cryo
      TEM). Viscometry shows that the system underwent several morphological
      transitions with the increase in concentration of C(8)OH (regions I-IV). At low
      octanol concentration (region I), DLS analysis showed an increase in the apparent
      hydrodynamic diameter of the micelles with the addition of C(8)OH which was
      supported by cryo-TEM and rheology. With further addition of C(8)OH, transition
      of the elongated micelles occurred to a viscoelastic fluid comprising entangled
      wormlike micelles (region II), for which rheological data can be described by the
      Maxwell model. Further, the wormlike micelles transform to vesicles at [C(8)OH] ~
      0.020 M (region III). This transition and the consequent changes in the fluid
      response can be explained in terms of vesicle formation caused by further
      addition of C(8)OH. Beyond this concentration (region IV), vesicles are the
      predominant microstructures in the system which shows unusual temperature
      response.

PMID- 21197966
TI  - Communication: Decoherence in a nonequilibrium environment: an analytically
      solvable model.
AB  - We describe an analytically solvable model of quantum decoherence in a
      nonequilibrium environment. The model considers the effect of a bath driven from
      equilibrium by, for example, an ultrafast excitation of a quantum chromophore.
      The nonequilibrium response of the environment is represented by a nonstationary
      random function corresponding to the fluctuating transition frequency between two
      quantum states coupled to the surroundings. The nonstationary random function is
      characterized by a Fourier series with the phase of each term starting initially
      with a definite value across the ensemble but undergoing random diffusion with
      time. The decay of the off-diagonal density matrix element is shown to depend
      significantly on the particular pattern of initial phases of the terms in the
      Fourier series, or equivalently, the initial phases of bath modes coupled to the
      quantum subsystem. This suggests the possibility of control of quantum
      decoherence by the detailed properties of an environment that is driven from
      thermal equilibrium.

PMID- 21197968
TI  - Communication: Ionization potentials in the limit of large atomic number.
AB  - By extrapolating the energies of nonrelativistic atoms and their ions with up to
      3000 electrons within Kohn-Sham density functional theory, we find that the
      ionization potential remains finite and increases across a row of the periodic
      table, even as Z -> infinity. The local density approximation for the exchange
      contribution becomes more accurate (or even exact) in this limit. Extended Thomas
      Fermi theory matches the shell average of both the ionization potential and
      density change.

PMID- 21197967
TI  - Communication: Polarization-angle-scanning two-dimensional infrared spectroscopy
      of antiparallel beta-sheet polypeptide: additional dimensions in two-dimensional
      optical spectroscopy.
AB  - A theoretical description of polarization-angle-scanning (PAS) two-dimensional
      infrared (2DIR) spectroscopy, where the incident beam polarization directions are
      considered to be novel dimensions in coherent two-dimensional (2D) optical
      spectroscopy, is presented. To shed light on the underlying principles and to
      illustrate a potential use of this measurement method, we investigate the PAS
      2DIR spectroscopy of an alanine-based antiparallel beta-sheet, using the
      relationships between cross-peak amplitudes and incident beam polarization
      directions and carrying out numerical simulations. The numerically simulated PAS
      2DIR spectra of the antiparallel beta-sheet show that the magnitude and sign of
      the cross peak reflecting the correlation between the two characteristic amide I
      vibrations change for varying beam polarization directions. This suggests that
      each individual cross peak in a given 2D spectrum can be selectively eliminated
      with an appropriate beam polarization configuration, which in turn provides
      information on the transition dipole angle and possibly on the structure of
      coupled multichromophoric systems. This novel measurement method combining the
      polarization-angle-scanning technique with 2D vibrational or electronic
      spectroscopy would be a useful tool for probing structural changes of
      nonequilibrium molecular systems and to investigate transfers of population and
      coherence by monitoring the time-dependent changes of angles between transition
      dipoles.

PMID- 21197969
TI  - Communication: Evidence of hydrated electrons injected by a metallic electrode in
      a high voltage system.
AB  - In this work it a strong evidence of the hydrated electrons production was shown
      in a film of condensed water, by directing the injection of electrons in
      localized and/or delocalized water electronic states using a system of high
      voltage made in laboratory. The results show that the water layers on the silica
      particles are electrically charged by injection of electrons from a metal
      electrode when silica is placed in high electric field. This charging process
      also appears to depend on the thickness of these water layers and of the spatial
      arrangement required by the silica surface.

PMID- 21197970
TI  - Sampling rare events in nonequilibrium and nonstationary systems.
AB  - Although many computational methods for rare event sampling exist, this type of
      calculation is not usually practical for general nonequilibrium conditions, with
      macroscopically irreversible dynamics and away from both stationary and
      metastable states. A novel method for calculating the time-series of the
      probability of a rare event is presented which is designed for these conditions.
      The method is validated for the cases of the Glauber-Ising model under time
      varying shear flow, the Kawasaki-Ising model after a quench into the region
      between nucleation dominated and spinodal decomposition dominated phase change
      dynamics, and the parallel open asymmetric exclusion process. The method requires
      a subdivision of the phase space of the system: it is benchmarked and found to
      scale well for increasingly fine subdivisions, meaning that it can be applied
      without detailed foreknowledge of the physically important reaction pathways.

PMID- 21197971
TI  - A simple protocol for the probability weights of the simulated tempering
      algorithm: applications to first-order phase transitions.
AB  - The simulated tempering (ST) is an important method to deal with systems whose
      phase spaces are hard to sample ergodically. However, it uses accepting
      probabilities weights, which often demand involving and time consuming
      calculations. Here it is shown that such weights are quite accurately obtained
      from the largest eigenvalue of the transfer matrix--a quantity straightforward to
      compute from direct Monte Carlo simulations--thus simplifying the algorithm
      implementation. As tests, different systems are considered, namely, Ising, Blume
      Capel, Blume-Emery-Griffiths, and Bell-Lavis liquid water models. In particular,
      we address first-order phase transition at low temperatures, a regime notoriously
      difficulty to simulate because the large free-energy barriers. The good results
      found (when compared with other well established approaches) suggest that the ST
      can be a valuable tool to address strong first-order phase transitions, a
      possibility still not well explored in the literature.

PMID- 21197972
TI  - Nonlocal van der Waals density functional: the simpler the better.
AB  - We devise a nonlocal correlation energy functional that describes the entire
      range of dispersion interactions in a seamless fashion using only the electron
      density as input. The new functional is considerably simpler than its
      predecessors of a similar type. The functional has a tractable and robust
      analytic form that lends itself to efficient self-consistent implementation. When
      paired with an appropriate exchange functional, our nonlocal correlation model
      yields accurate interaction energies of weakly-bound complexes, not only near the
      energy minima but also far from equilibrium. Our model exhibits an outstanding
      precision at predicting equilibrium intermonomer separations in van der Waals
      complexes. It also gives accurate covalent bond lengths and atomization energies.
      Hence the functional proposed in this work is a computationally inexpensive
      electronic structure tool of broad applicability.

PMID- 21197973
TI  - Effective local potentials for excited states.
AB  - The constrained variational Hartree-Fock method for excited states of the same
      symmetry as the ground state [Chem. Phys. Lett. 287, 189 (1998)] is combined with
      the effective local potential (ELP) method [J. Chem. Phys. 125, 081104 (2006)] to
      generate Kohn-Sham-type exact-exchange potentials for singly excited states of
      many-electron systems. Illustrative examples include the three lowest (2)S states
      of the Li and Na atoms and the three lowest (3)S states of He and Be. For the
      systems studied, excited-state ELPs differ from the corresponding ground-state
      potentials in two respects: They are less negative and have small additional
      "bumps" in the outer electron region. The technique is general and can be used to
      approximate excited-state exchange-correlation potentials for other orbital
      dependent functionals.

PMID- 21197974
TI  - Electronic coupling matrix elements from charge constrained density functional
      theory calculations using a plane wave basis set.
AB  - We present a plane wave basis set implementation for the calculation of
      electronic coupling matrix elements of electron transfer reactions within the
      framework of constrained density functional theory (CDFT). Following the work of
      Wu and Van Voorhis [J. Chem. Phys. 125, 164105 (2006)], the diabatic
      wavefunctions are approximated by the Kohn-Sham determinants obtained from CDFT
      calculations, and the coupling matrix element calculated by an efficient
      integration scheme. Our results for intermolecular electron transfer in small
      systems agree very well with high-level ab initio calculations based on
      generalized Mulliken-Hush theory, and with previous local basis set CDFT
      calculations. The effect of thermal fluctuations on the coupling matrix element
      is demonstrated for intramolecular electron transfer in the tetrathiafulvalene
      diquinone (Q-TTF-Q(-)) anion. Sampling the electronic coupling along density
      functional based molecular dynamics trajectories, we find that thermal
      fluctuations, in particular the slow bending motion of the molecule, can lead to
      changes in the instantaneous electron transfer rate by more than an order of
      magnitude. The thermal average, (<|H(ab)|(2)>)(1/2)=6.7 mH, is significantly
      higher than the value obtained for the minimum energy structure, |H(ab)|=3.8 mH.
      While CDFT in combination with generalized gradient approximation (GGA)
      functionals describes the intermolecular electron transfer in the studied systems
      well, exact exchange is required for Q-TTF-Q(-) in order to obtain coupling
      matrix elements in agreement with experiment (3.9 mH). The implementation
      presented opens up the possibility to compute electronic coupling matrix elements
      for extended systems where donor, acceptor, and the environment are treated at
      the quantum mechanical (QM) level.

PMID- 21197975
TI  - Multidimensional optical spectroscopy of a single molecule in a current-carrying
      state.
AB  - The nonlinear optical signals from an open system consisting of a molecule
      connected to metallic leads, in response to a sequence of impulsive pulses, are
      calculated using a superoperator formalism. Two detection schemes are considered:
      coherent stimulated emission and incoherent fluorescence. The two provide similar
      but not identical information. The necessary superoperator correlation functions
      are evaluated either by converting them to ordinary (Hilbert space) operators
      which are then expanded in many-body states, or by using Wick's theorem for
      superoperators to factorize them into nonequilibrium two point Green's functions.
      As an example we discuss a stimulated Raman process that shows resonances
      involving two different charge states of the molecule in the same signal.

PMID- 21197976
TI  - Density-functional expansion methods: evaluation of LDA, GGA, and meta-GGA
      functionals and different integral approximations.
AB  - We extend the Kohn-Sham potential energy expansion (VE) to include variations of
      the kinetic energy density and use the VE formulation with a 6-31G* basis to
      perform a "Jacob's ladder" comparison of small molecule properties using density
      functionals classified as being either LDA, GGA, or meta-GGA. We show that the VE
      reproduces standard Kohn-Sham DFT results well if all integrals are performed
      without further approximation, and there is no substantial improvement in using
      meta-GGA functionals relative to GGA functionals. The advantages of using GGA
      versus LDA functionals becomes apparent when modeling hydrogen bonds. We
      furthermore examine the effect of using integral approximations to compute the
      zeroth-order energy and first-order matrix elements, and the results suggest that
      the origin of the short-range repulsive potential within self-consistent charge
      density-functional tight-binding methods mainly arises from the approximations
      made to the first-order matrix elements.

PMID- 21197977
TI  - Comparison of one-particle basis set extrapolation to explicitly correlated
      methods for the calculation of accurate quartic force fields, vibrational
      frequencies, and spectroscopic constants: application to H2O, N2H+, NO2+, and
      C2H2.
AB  - One-particle basis set extrapolation is compared with one of the new R12 methods
      for computing highly accurate quartic force fields (QFFs) and spectroscopic data,
      including molecular structures, rotational constants, and vibrational frequencies
      for the H(2)O, N(2)H(+), NO(2)(+), and C(2)H(2) molecules. In general, agreement
      between the spectroscopic data computed from the best R12 and basis set
      extrapolation methods is very good with the exception of a few parameters for
      N(2)H(+) where it is concluded that basis set extrapolation is still preferred.
      The differences for H(2)O and NO(2)(+) are small and it is concluded that the
      QFFs from both approaches are more or less equivalent in accuracy. For C(2)H(2),
      however, a known one-particle basis set deficiency for C-C multiple bonds
      significantly degrades the quality of results obtained from basis set
      extrapolation and in this case the R12 approach is clearly preferred over one
      particle basis set extrapolation. The R12 approach used in the present study was
      modified in order to obtain high precision electronic energies, which are needed
      when computing a QFF. We also investigated including core-correlation explicitly
      in the R12 calculations, but conclude that current approaches are lacking. Hence
      core-correlation is computed as a correction using conventional methods.
      Considering the results for all four molecules, it is concluded that R12 methods
      will soon replace basis set extrapolation approaches for high accuracy electronic
      structure applications such as computing QFFs and spectroscopic data for
      comparison to high-resolution laboratory or astronomical observations, provided
      one uses a robust R12 method as we have done here. The specific R12 method used
      in the present study, CCSD(T)(R12), incorporated a reformulation of one
      intermediate matrix in order to attain machine precision in the electronic
      energies. Final QFFs for N(2)H(+) and NO(2)(+) were computed, including basis set
      extrapolation, core-correlation, scalar relativity, and higher-order correlation
      and then used to compute highly accurate spectroscopic data for all
      isotopologues. Agreement with high-resolution experiment for (14)N(2)H(+) and
      (14)N(2)D(+) was excellent, but for (14)N(16)O(2)(+) agreement for the two
      stretching fundamentals is outside the expected residual uncertainty in the
      theoretical values, and it is concluded that there is an error in the
      experimental quantities. It is hoped that the highly accurate spectroscopic data
      presented for the minor isotopologues of N(2)H(+) and NO(2)(+) will be useful in
      the interpretation of future laboratory or astronomical observations.

PMID- 21197978
TI  - Aggregation work at polydisperse micellization: ideal solution and "dressed
      micelle" models comparing to molecular dynamics simulations.
AB  - General thermodynamic relations for the work of polydisperse micelle formation in
      the model of ideal solution of molecular aggregates in nonionic surfactant
      solution and the model of "dressed micelles" in ionic solution have been
      considered. In particular, the dependence of the aggregation work on the total
      concentration of nonionic surfactant has been analyzed. The analogous dependence
      for the work of formation of ionic aggregates has been examined with regard to
      existence of two variables of a state of an ionic aggregate, the aggregation
      numbers of surface active ions and counterions. To verify the thermodynamic
      models, the molecular dynamics simulations of micellization in nonionic and ionic
      surfactant solutions at two total surfactant concentrations have been performed.
      It was shown that for nonionic surfactants, even at relatively high total
      surfactant concentrations, the shape and behavior of the work of polydisperse
      micelle formation found within the model of the ideal solution at different total
      surfactant concentrations agrees fairly well with the numerical experiment. For
      ionic surfactant solutions, the numerical results indicate a strong screening of
      ionic aggregates by the bound counterions. This fact as well as independence of
      the coefficient in the law of mass action for ionic aggregates on total
      surfactant concentration and predictable behavior of the "waterfall" lines of
      surfaces of the aggregation work upholds the model of "dressed" ionic aggregates.

PMID- 21197979
TI  - Local CC2 response method for triplet states based on Laplace transform:
      excitation energies and first-order properties.
AB  - A new multistate local CC2 response method for calculating excitation energies
      and first-order properties of excited triplet states in extended molecular
      systems is presented. The Laplace transform technique is employed to partition
      the left/right local CC2 eigenvalue problems as well as the linear equations
      determining the Lagrange multipliers needed for the properties. The doubles part
      in the equations can then be inverted on-the-fly and only effective equations for
      the singles part must be solved iteratively. The local approximation presented
      here is adaptive and state-specific. The density-fitting method is utilized to
      approximate the electron-repulsion integrals. The accuracy of the new method is
      tested by comparison to canonical reference values for a set of 12 test molecules
      and 62 excited triplet states. As an illustrative application example, the lowest
      four triplet states of 3-(5-(5-(4-(bis(4-(hexyloxy)phenyl)amino)phenyl)thiophene
      2-yl)thiophene-2-yl)-2-cyanoacrylic acid, an organic sensitizer for solar-cell
      applications, are computed in the present work. No triplet charge-transfer states
      are detected among these states. This situation contrasts with the singlet states
      of this molecule, where the lowest singlet state has been recently found to
      correspond to an excited state with a pronounced charge-transfer character having
      a large transition strength.

PMID- 21197980
TI  - A smooth, nonsingular, and faithful discretization scheme for polarizable
      continuum models: the switching/Gaussian approach.
AB  - Polarizable continuum models (PCMs) are a widely used family of implicit solvent
      models based on reaction-field theory and boundary-element discretization of the
      solute/continuum interface. An often overlooked aspect of these theories is that
      discretization of the interface typically does not afford a continuous potential
      energy surface for the solute. In addition, we show that discretization can lead
      to numerical singularities and violations of exact variational conditions. To fix
      these problems, we introduce the switching/Gaussian (SWIG) method, a
      discretization scheme that overcomes several longstanding problems with PCMs. Our
      approach generalizes a procedure introduced by York and Karplus [J. Phys. Chem. A
      103, 11060 (1999)], extending it beyond the conductor-like screening model.
      Comparison to other purportedly smooth PCM implementations reveals certain
      artifacts in these alternative approaches, which are avoided using the SWIG
      methodology. The versatility of our approach is demonstrated via geometry
      optimizations, vibrational frequency calculations, and molecular dynamics
      simulations, for solutes described using quantum mechanics and molecular
      mechanics.

PMID- 21197981
TI  - An adaptive coupled-cluster theory: @CC approach.
AB  - A formulation of an adaptive coupled-cluster theory is presented. The method
      automatically "adjusts" to any state of an electronic system and converges to the
      full CI limit, thus being capable of describing both single- and multireference
      phenomena. Adaptivity is accomplished through a guided selection of a compact set
      of cluster amplitudes as required for a proper description of the electronic
      system under consideration. The approach suggested is of "black-box" type. A
      special importance-selection function (discriminatory function) is explicitly
      introduced for the guided selection of variables involved in the theoretical
      model. The method is tested on molecules which exhibit strong multireference
      character in the region of chemical bond elongation. An unambiguous comparison
      with formally exact full CI solutions shows that the method is capable of
      providing mHartee accuracy using a rather compact set of cluster amplitudes.

PMID- 21197982
TI  - The flux-flux correlation function for anharmonic barriers.
AB  - The flux-flux correlation function formalism is a standard and widely used
      approach for the computation of reaction rates. In this paper we introduce a
      method to compute the classical and quantum flux-flux correlation functions for
      anharmonic barriers essentially analytically through the use of the classical and
      quantum normal forms. In the quantum case we show that for a general f degree-of
      freedom system having an index one saddle the quantum normal form reduces the
      computation of the flux-flux correlation function to that of an effective one
      dimensional anharmonic barrier. The example of the computation of the quantum
      flux-flux correlation function for a fourth order anharmonic barrier is worked
      out in detail, and we present an analytical expression for the quantum mechanical
      microcanonical flux-flux correlation function. We then give a discussion of the
      short-time and harmonic limits.

PMID- 21197983
TI  - Escape from the potential well: competition between long jumps and long waiting
      times.
AB  - Within a concept of the fractional diffusion equation and subordination, the
      paper examines the influence of a competition between long waiting times and long
      jumps on the escape from the potential well. Applying analytical arguments and
      numerical methods, we demonstrate that the presence of long waiting times
      distributed according to a power-law distribution with a diverging mean leads to
      very general asymptotic properties of the survival probability. The observed
      survival probability asymptotically decays like a power law whose form is not
      affected by the value of the exponent characterizing the power law jump length
      distribution. It is demonstrated that this behavior is typical of and generic for
      systems exhibiting long waiting times. We also show that the survival probability
      has a universal character not only asymptotically, but also at small times.
      Finally, it is indicated which properties of the first passage time density are
      sensitive to the exact value of the exponent characterizing the jump length
      distribution.

PMID- 21197984
TI  - Crystal nucleation of hard spheres using molecular dynamics, umbrella sampling,
      and forward flux sampling: a comparison of simulation techniques.
AB  - Over the last number of years several simulation methods have been introduced to
      study rare events such as nucleation. In this paper we examine the crystal
      nucleation rate of hard spheres using three such numerical techniques: molecular
      dynamics, forward flux sampling, and a Bennett-Chandler-type theory where the
      nucleation barrier is determined using umbrella sampling simulations. The
      resulting nucleation rates are compared with the experimental rates of Harland
      and van Megen [Phys. Rev. E 55, 3054 (1997)], Sinn et al. [Prog. Colloid Polym.
      Sci. 118, 266 (2001)], Schatzel and Ackerson [Phys. Rev. E 48, 3766 (1993)], and
      the predicted rates for monodisperse and 5% polydisperse hard spheres of Auer and
      Frenkel [Nature 409, 1020 (2001)]. When the rates are examined in units of the
      long-time diffusion coefficient, we find agreement between all the theoretically
      predicted nucleation rates, however, the experimental results display a markedly
      different behavior for low supersaturation. Additionally, we examined the
      precritical nuclei arising in the molecular dynamics, forward flux sampling, and
      umbrella sampling simulations. The structure of the nuclei appears independent of
      the simulation method, and in all cases, the nuclei contains on average
      significantly more face-centered-cubic ordered particles than hexagonal-close
      packed ordered particles.

PMID- 21197985
TI  - Understanding free-energy perturbation calculations through a model of harmonic
      oscillators: theory and implications to improve the sampling efficiency by
      molecular simulation.
AB  - Free-energy perturbation calculation is frequently used to calculate free-energy
      differences because it is easy to implement and the computation is fast. However,
      the calculation is subject to large inaccuracies in some circumstances due to the
      insufficient sampling of the relevant tails of the energy-difference
      distributions. Here we expand this knowledge of insufficient sampling into a two
      dimensional (2D) energy space using a model of harmonic oscillators. We show
      analytically the relation between the energies of the sampling system and those
      of the desired target energy spaces, which provide the basis to understand the
      difficulties in free-energy perturbation calculations. We clarify the reasons of
      the inaccurate calculation in the different harmonic cases that stem from the
      spatial separations of the reference and the target energy pairs located in the
      two-dimensional energy space. The potential-energy space introduced into this 2D
      energy-space model provides additional clues to improve the sampling efficiency.
      Based on this understanding, we propose two ways to calculate the free-energy
      differences using the two schemes of the distribution method. We show that the
      distribution method implemented in the appropriate energy space--the energy
      difference space and the potential-energy space, respectively--can improve the
      calculation of free energies in different circumstances. This analysis implies
      that the sampling can be improved if it is directed toward the appropriate region
      in the potential-energy space, which is easily implemented in various types of
      free-energy calculations. To test this, we calculate the free-energy surface of
      alanine dipeptide in gas phase and in aqueous phase, respectively. We demonstrate
      that the free-energy surface calculation is improved when the biased sampling of
      the potential energy is integrated into the sampling scheme.

PMID- 21197986
TI  - A cutoff phenomenon in accelerated stochastic simulations of chemical kinetics
      via flow averaging (FLAVOR-SSA).
AB  - We present a simple algorithm for the simulation of stiff, discrete-space,
      continuous-time Markov processes. The algorithm is based on the concept of flow
      averaging for the integration of stiff ordinary and stochastic differential
      equations and ultimately leads to a straightforward variation of the the well
      known stochastic simulation algorithm (SSA). The speedup that can be achieved by
      the present algorithm [flow averaging integrator SSA (FLAVOR-SSA)] over the
      classical SSA comes naturally at the expense of its accuracy. The error of the
      proposed method exhibits a cutoff phenomenon as a function of its speed-up,
      allowing for optimal tuning. Two numerical examples from chemical kinetics are
      provided to illustrate the efficiency of the method.

PMID- 21197987
TI  - Ground and excited electronic states of azobenzene: a quantum Monte Carlo study.
AB  - Large-scale quantum Monte Carlo (QMC) calculations of ground and excited singlet
      states of both conformers of azobenzene are presented. Remarkable accuracy is
      achieved by combining medium accuracy quantum chemistry methods with QMC. The
      results not only reproduce measured values with chemical accuracy but the
      accuracy is sufficient to identify part of experimental results which appear to
      be biased. Novel analysis of nodal surface structure yields new insights and
      control over their convergence, providing boost to the chemical accuracy
      electronic structure methods of large molecular systems.

PMID- 21197988
TI  - Metastable anions of dinitrobenzene: resonances for electron attachment and
      kinetic energy release.
AB  - Attachment of free, low-energy electrons to dinitrobenzene (DNB) in the gas phase
      leads to DNB(-) as well as several fragment anions. DNB(-), (DNB-H)(-), (DNB-NO)(
      ), (DNB-2NO)(-), and (DNB-NO(2))(-) are found to undergo metastable
      (unimolecular) dissociation. A rich pattern of resonances in the yield of these
      metastable reactions versus electron energy is observed; some resonances are
      highly isomer-specific. Most metastable reactions are accompanied by large
      average kinetic energy releases (KER) that range from 0.5 to 1.32 eV, typical of
      complex rearrangement reactions, but (1,3-DNB-H)(-) features a resonance with a
      KER of only 0.06 eV for loss of NO. (1,3-DNB-NO)(-) offers a rare example of a
      sequential metastable reaction, namely, loss of NO followed by loss of CO to
      yield C(5)H(4)O(-) with a large KER of 1.32 eV. The G4(MP2) method is applied to
      compute adiabatic electron affinities and reaction energies for several of the
      observed metastable channels.

PMID- 21197989
TI  - Microwave spectra, structure, and dynamics of the weakly bound complex, N2 CO2.
AB  - The Fourier transform microwave spectra of the various isotopologs of the weakly
      bound complex of carbon dioxide with the most abundant molecule in the
      atmosphere, nitrogen, have been measured. The structure of the complex has been
      determined and evidence for the inversion of the N(2) is presented. The molecule
      is T-shaped, with the OCO forming the cross of the T, a structure consistent with
      that deduced from a previous rotationally resolved infrared experiment. A
      significant wide-amplitude bending motion of the N(2) is deduced from the values
      of the (nearly identical) nuclear quadrupole coupling constants of the nitrogen
      nuclei. The spectroscopic results are compared with high-quality ab initio
      calculations. We examine the consequences of the N(2) CO(2) complex formation in
      the atmosphere upon the greenhouse warming potential of carbon dioxide.

PMID- 21197990
TI  - Dynamics and mechanism of the non-adiabatic transitions from the ungerade
      I2(D0+u) state induced by collisions with rare gas atoms.
AB  - The stepwise three-photon two-color laser excitation scheme is used for selective
      population of the first-tier ion-pair D0(+)(u) state of molecular iodine.
      Collection and analysis of the luminescence after the excitation of the v(D) = 6,
      8, 13 and 18 vibronic levels of the D state in the pure iodine vapor and the gas
      phase mixtures with He, Ar and Xe provide the total and, whenever possible,
      partial rate constants for the collision-induced non-adiabatic transitions to the
      other ion-pair states of the first tier. Comparison with the analogous data
      obtained previously for the non-adiabatic transitions from the E0(+)(g) state
      reveals the similarity between two cases. For He, the D <-> E transitions are
      preferable, whereas for Ar and Xe transitions to the D' and beta states dominate
      at v(D) = 6, 8 and 13, in accord with the statistical considerations. Efficient
      population of the delta state at v(D) = 18 in Ar and Xe is the most prominent non
      statistical feature observed. The vibrational product state distributions for the
      D -> E transitions are also obtained. In contrast to the previously studied E ->
      D transition, they show significant positive vibronic energy transfer. The
      measurements for He and Ar are accompanied by the quantum scattering calculations
      that reproduce well the main qualitative features of the experimental results.

PMID- 21197991
TI  - The Zeeman effect and hyperfine interactions in J = 1-0 transitions of CH+ and
      its isotopologues.
AB  - The J = 1-0 transitions of (12)CH(+), (13)CH(+), and (12)CD(+) in the ground
      X(1)Sigma(+) state have been unambiguously identified by using an extended
      negative glow discharge as an ion source. Unexpectedly large Zeeman splittings
      have been observed, and the (13)CH(+) line exhibits nuclear spin-rotation
      hyperfine splitting in addition to the Zeeman effect. The nuclear spin-rotation
      coupling constant was determined to be 1.087(50) MHz for the (13)C species. The
      rotational g-factor is found to be -7.65(29), in terms of the nuclear magneton
      for the J = 1 and v = 0 state, more than an order of magnitude larger than values
      for typical diamagnetic closed shell molecules. These larger than usual magnetic
      interactions for a (1)Sigma molecule are caused by the large rotational energy
      and relatively small excitation energy of the excited A(1)Pi state. The effective
      g-factor and the spin-rotation coupling constant obtained by ab initio
      calculations agree very well with the experimentally determined values.

PMID- 21197992
TI  - The role of atomic excited states of Au on N2O capture and activation: a
      multireference second-order perturbation theory study.
AB  - Nitrous oxide (N(2)O) is an intermediate compound formed during catalysis
      occurring in automobile exhaust pipes. Atomic Au in its ground state is unable to
      react with N(2)O, however, several Au excited states are bound to N(2)O, but not
      all of these states are able to activate N(2)O bonds. In this work, N(2)O capture
      and activation by a single Au atom are studied considering Au in the ground and
      excited states with multiplicities = 2, 4 and 6. The Au + N(2)O reactions are
      studied at multireference second-order perturbation level of theory using C(s)
      symmetry. The AuN(2)O ((4)A', (4)A'', (6)A' and (6)A'') adducts are spontaneously
      created from Au excited states. From these complexes, only the (4)A', (6)A' and
      (6)A'' states exhibit N(2)O activation reaction paths yielding N(2,) NO and O
      atoms as end products when N(2)O approaches Au excited states side-on. Cations
      both ground and excited states, capture N(2)O although only the Au(+) ((5)A') +
      N(2)O ((1)Sigma(+)) -> NAuNO(+) ((5)A') reaction (for the end-on and side-on
      approaches) shows N(2)O activation with N-N bond breaking. In the case of Au
      anions, the ground state and most of the excited states capture N(2)O and
      activation takes place according to Au(-) ((3)A', (5)A', (5)A'') + N(2)O
      ((1)Sigma(+)) -> AuO(-) ((3)A', (5)A', (5)A'') + N(2)(g) for the N(2)O end-on
      approach by the oxygen atom. The reaction paths show a metal-gas dative covalent
      bonding character. Mulliken charge population analysis obtained for the active
      states shows that the binding is done through charge donation and retro-donation
      between the metal and the N(2)O molecule.

PMID- 21197993
TI  - Influence of nuclear exchange on nonadiabatic electron processes in H(+)+H2
      collisions.
AB  - H(+)+H(2) collisions are studied by means of a semiclassical approach that
      explicitly accounts for nuclear rearrangement channels in nonadiabatic electron
      processes. A set of classical trajectories is used to describe the nuclear
      motion, while the electronic degrees of freedom are treated quantum mechanically
      in terms of a three-state expansion of the collision wavefunction. We describe
      electron capture and vibrational excitation, which can also involve nuclear
      exchange and dissociation, in the E = 2-1000 eV impact energy range. We compare
      dynamical results obtained with two parametrizations of the potential energy
      surface of H(3)(+) ground electronic state. Total cross sections for E > 10 eV
      agree with previous results using a vibronic close-coupling expansion, and with
      experimental data for E < 10 eV. Additionally, some prototypical features of both
      nuclear and electron dynamics at low E are discussed.

PMID- 21197994
TI  - Electronic and vibrational contributions to first hyperpolarizability of donor
      acceptor-substituted azobenzene.
AB  - In this study we report on the electronic and vibrational (hyper)polarizabilities
      of donor-acceptor-substituted azobenzene. It is observed that both electronic and
      vibrational contributions to the electric dipole first hyperpolarizability of
      investigated photoactive molecule substantially depend on the conformation. The
      contributions to the nuclear relaxation first hyperpolarizability are found to be
      quite important in the case of two considered isomers (cis and trans). Although
      the double-harmonic term is found to be the largest in terms of magnitude, it is
      shown that the total value of the nuclear relaxation contribution to vibrational
      first hyperpolarizability is a result of subtle interplay of higher-order
      contributions. As a part of the study, we also assess the performance of long
      range-corrected density functional theory in determining vibrational
      contributions to electric dipole (hyper)polarizabilities. In most cases, the
      applied long-range-corrected exchange-correlation potentials amend the drawbacks
      of their conventional counterparts.

PMID- 21197995
TI  - Photodissociation and photoionization of 2,5-dihydroxybenzoic acid at 193 and 355
      nm.
AB  - Photodissociation and photoionization of 2,5-dihydroxybenzoic acid (25DHBA), at
      193 and 355 nm were investigated separately in a molecular beam using multimass
      ion imaging techniques. Two channels competed after excitation by one 193 nm
      photon. One channel is dissociation from the repulsive excited state along O-H
      bond distance, resulting in H atom elimination from meta-OH functional group. The
      other channel is internal conversion to the ground state, followed by H(2)O
      elimination. Some of the fragments further proceeded to secondary dissociation.
      On the other hand, absorption of one 355 nm photon gave rise to H(2)O elimination
      channel on the ground state. Absorption of more than one 355 nm photon resulted
      in the three-body dissociation which also occurs on the ground state.
      Dissociation on the excited state does not play a role at 355 nm. The large
      concentration ratio (2*10(5)), between neutral fragments and cations produced
      from 355 nm multiphoton excitation indicates that internal conversion followed by
      dissociation, is the major channel for 355 nm multiphoton excitation. Multiphoton
      ionization is a minor channel. Multiphoton ionization of 25DHBA clusters only
      produces 25DHBA cations. Neither anion nor protonated 25DHBA cation were
      observed. It is very different from the ions produced from solid matrix-assisted
      laser desorption/ionization (MALDI), experiments. This suggests that protonated
      25DHBA and negatively charged 25DHBA generated in MALDI experiments does not
      simply result from the ionization following proton transfer reactions or charge
      transfer reactions of the clusters in the gas phase.

PMID- 21197996
TI  - The phase behavior of two-dimensional symmetrical mixtures.
AB  - Using Monte Carlo simulation methods in the grand canonical and semigrand
      canonical ensembles, we study the phase behavior of two-dimensional symmetrical
      binary mixtures of Lennard-Jones particles. We discuss the interplay between the
      demixing transition in a liquid and the freezing in detail. Phase diagrams for
      several systems characterized by different parameters describing interactions in
      the system are presented. It is explicitly demonstrated that different scenarios
      involving demixing and freezing transitions, described in our earlier paper [A.
      Patrykiejew and S. Sokolowski, Phys. Rev. E, 81, 012501 (2010)], are possible. In
      one class of systems, the lambda-line representing a continuous demixing
      transition in a liquid phase starts at the liquid side of either the vapor-liquid
      or liquid-solid coexistence. The second class involves the systems in which the
      lambda-line begins at the liquid side of the vapor-liquid coexistence, in the
      lower critical end point, and then terminates at the liquid side of the liquid
      solid coexistence, in the upper critical end point. It is also shown that in such
      systems the solid phase may undergo a demixing transition at the temperature
      above the upper critical end point.

PMID- 21197997
TI  - Macroscopic facilitation of glassy relaxation kinetics: ultrastable glass films
      with frontlike thermal response.
AB  - The recent experimental fabrication of ultrastable glass films, via vapor
      deposition [Swallen et al., Science 315, 353 (2007)] and the observation of
      frontlike response to the annealing of these films [Swallen et al., Phys. Rev.
      Lett. 102, 065503 (2009)] have raised important questions about the possibility
      of manipulating the properties of glass films and addressing fundamental
      questions about kinetics and thermodynamics of amorphous materials. Central to
      both of these issues is the need to establish the essential physics that governs
      the formation of the ultrastable films and their subsequent response. In this
      paper, we demonstrate that a generic model of glassy dynamics can account for the
      formation of ultrastable films, the associated enhancement of relaxation rates by
      a factor of 10(5), the observation of frontlike response to temperature jumps and
      the temperature dependence of the front velocity.

PMID- 21197998
TI  - Two-photon resonant hyperpolarizability of an H-shaped molecule studied by
      wavelength-tunable hyper-Rayleigh scattering.
AB  - Wavelength dependent hyper-Rayleigh scattering measurements have been performed
      by using a fluorescence spectrometer. With this detection strategy, first
      molecular hyperpolarizability (beta) of a dual charge-transfer (H-shaped)
      chromophore and its monomer have been measured in two-photon resonance range from
      670 to 950 nm as well as at off-resonance of 1064 nm. The absorption and
      resonance hyper-Rayleigh profiles can be simulated reasonably well with a common
      set of parameters. In addition, both resonance and off-resonance results show
      that beta(0) per chromophore has a remarkable enhancement for the H-shaped
      molecule as large as 1.7, compared with that of the monomer, which could be
      ascribed to two physical effects: (1) coherent enhancement of two chromophores
      and (2) intramolecular dipole-dipole interaction, which was confirmed by their
      fluorescence-decay behaviors.

PMID- 21197999
TI  - Infrared and Raman line shapes for ice Ih. II. H2O and D2O.
AB  - We present a theoretical study of infrared and Raman line shapes of
      polycrystalline and single crystal ice Ih, for both water and heavy water, at 1,
      125, and 245 K. Our calculations involve a mixed quantum/classical approach, a
      new water simulation model with explicit three-body interactions, transition
      frequency and dipole maps, and intramolecular and intermolecular vibrational
      coupling maps. Our theoretical spectra are in reasonable agreement with
      experimental spectra (available only near the two higher temperatures). We trace
      the origins of the different spectral peaks to weak and strong intermolecular
      couplings. We also discuss the delocalization of the vibrational eigenstates in
      terms of the competing effects of disorder and coupling.

PMID- 21198000
TI  - Lock-exchange experiments with an autocatalytic reaction front.
AB  - A viscous lock-exchange gravity current corresponds to the reciprocal exchange of
      two fluids of different densities in a horizontal channel. The resulting front
      between the two fluids spreads as the square root of time, with a diffusion
      coefficient reflecting the buoyancy, viscosity, and geometrical configuration of
      the current. On the other hand, an autocatalytic reaction front between a
      reactant and a product may propagate as a solitary wave, namely, at a constant
      velocity and with a stationary concentration profile, resulting from the balance
      between molecular diffusion and chemical reaction. In most systems, the fluid
      left behind the front has a different density leading to a lock-exchange
      configuration. We revisit, with a chemical reaction, the classical situation of
      lock-exchange. We present an experimental analysis of buoyancy effects on the
      shape and the velocity of the iodate arsenous acid autocatalytic reaction fronts,
      propagating in horizontal rectangular channels and for a wide range of aspect
      ratios (1/3 to 20) and cylindrical tubes. We do observe stationary-shaped fronts,
      spanning the height of the cell and propagating along the cell axis. Our data
      support the contention that the front velocity and its extension are linked to
      each other and that their variations scale with a single variable involving the
      diffusion coefficient of the lock-exchange in the absence of chemical reaction.
      This analysis is supported by results obtained with lattice Bathnagar-Gross-Krook
      (BGK) simulations Jarrige et al. [Phys. Rev. E 81, 06631 (2010)], in other
      geometries (like in 2D simulations by Rongy et al. [J. Chem. Phys. 127, 114710
      (2007)] and experiments in cylindrical tubes by Pojman et al. [J. Phys. Chem. 95,
      1299 (1991)]), and for another chemical reaction Schuszter et al. [Phys. Rev. E
      79, 016216 (2009)].

PMID- 21198001
TI  - Effects of the attractive interactions in the thermodynamic, dynamic, and
      structural anomalies of a two length scale potential.
AB  - Using molecular dynamic simulations, we study a system of particles interacting
      through a continuous core-softened potentials consisting of a hard core, a
      shoulder at closest distances, and an attractive well at further distance. We
      obtain the pressure-temperature phase diagram of this system for various depths
      of the tunable attractive well. Since this is a two length scale potential,
      density, diffusion, and structural anomalies are expected. We show that the
      effect of increasing the attractive interaction between the molecules is to
      shrink the region in pressure in which the density and the diffusion anomalies
      are present. If the attractive forces are too strong, particle will be
      predominantly in one of the two length scales and no density of diffusion anomaly
      is observed. The structural anomalous region is present for all the cases.

PMID- 21198002
TI  - Density functional theory of liquid crystals and surface anchoring: hard Gaussian
      overlap-sphere and hard Gaussian overlap-surface potentials.
AB  - This article applies the density functional theory to confined liquid crystals,
      comprised of ellipsoidal shaped particles interacting through the hard Gaussian
      overlap (HGO) potential. The extended restricted orientation model proposed by
      Moradi and co-workers [J. Phys.: Condens. Matter 17, 5625 (2005)] is used to
      study the surface anchoring. The excess free energy is calculated as a functional
      expansion of density around a reference homogeneous fluid. The pair direct
      correlation function (DCF) of a homogeneous HGO fluid is approximated, based on
      the optimized sum of Percus-Yevick and Roth DCF for hard spheres; the anisotropy
      introduced by means of the closest approach parameter, the expression proposed by
      Marko [Physica B 392, 242 (2007)] for DCF of HGO, and hard ellipsoids were used.
      In this study we extend an our previous work [Phys. Rev. E 72, 061706 (2005)] on
      the anchoring behavior of hard particle liquid crystal model, by studying the
      effect of changing the particle-substrate contact function instead of hard needle
      wall potentials. We use the two particle-surface potentials: the HGO-sphere and
      the HGO-surface potentials. The average number density and order parameter
      profiles of a confined HGO fluid are obtained using the two particle-wall
      potentials. For bulk isotropic liquid, the results are in agreement with the
      Monte Carlo simulation of Barmes and Cleaver [Phys. Rev. E 71, 021705 (2005)].
      Also, for the bulk nematic phase, the theory gives the correct density profile
      and order parameter between the walls.

PMID- 21198003
TI  - Understanding the optical spectroscopy of amphiphilic molecular rectifiers: a
      density functional approach.
AB  - We present results of first principles density functional theory calculations of
      the electronic and atomic structural properties of model Z-type Langmuir-Blodgett
      (LB) layers comprising amphiphilic quinolinium tricyanoquinodimethanide (Q3CNQ)
      chromophores. We find that the chromophore electronic ground state is not as
      clearly "zwitterionic" as required by models to explain electrical rectification
      purportedly seen in such systems. The computed visible region transitions are not
      what have been assumed to be the intervalence charge transfer bands seen in the
      visible region of molecules in Z-type LB films. Our own LB deposition and
      spectroscopic studies suggest that almost all visible region features previously
      seen may be ascribed to aggregates. The calculated lowest energy electronic
      excitation between HOMO and LUMO levels, which is located in the near infrared
      region, has a transition moment aligned approximately 9 degrees  off the
      molecular long axis, and has a normalized oscillator strength of 1 order of
      magnitude higher than those of the visible region transitions. This most dominant
      feature has been neglected from discussions of Langmuir-Blodgett layer
      rectification but our own deposition studies show no sign of this feature,
      indicating that the structure of the modeled system differs from that of typical
      experimental structures. The model indicates that such idealized LB layer
      structures cannot confidently be invoked to explain their experimental optical or
      electrical properties.

PMID- 21198004
TI  - The effect of attractions on the local structure of liquids and colloidal fluids.
AB  - We revisit the role of attractions in liquids and apply these concepts to
      colloidal suspensions. Two means are used to investigate the structure; the pair
      correlation function and a recently developed topological method. The latter
      identifies structures topologically equivalent to ground state clusters formed by
      isolated groups of 5 <= m <= 13 particles, which are specific to the system under
      consideration. Our topological methodology shows that, in the case of Lennard
      Jones, the addition of attractions increases the system's ability to form larger
      (m >= 8) clusters, although pair-correlation functions are almost identical.
      Conversely, in the case of short-ranged attractions, pair correlation functions
      show a significant response to adding attraction, while the liquid structure
      exhibits a strong decrease in clustering upon adding attractions. Finally, a
      compressed, weakly interacting system shows a similar pair structure and
      topology.

PMID- 21198005
TI  - Simulations of polyelectrolyte dynamics in an externally applied electric field
      in confined geometry.
AB  - We consider the dynamics of charged polymers in free solution in a slit geometry
      under the influence of an electrical field, applied at an angle to the plane
      parallel walls of the confinement. The simulations are carried out using the
      Brownian dynamics method with explicit counterions and implicit hydrodynamics.
      The hydrodynamic interactions between all the particles and the plane parallel
      walls are taken into account using a diffusion matrix which depends on slit
      geometry and the actual polyelectrolyte-solute conformations. We observe a
      selective transport of the charged polymers, as a function of the degree of
      polymerization and slit height.

PMID- 21198006
TI  - Simulations of the gyroid phase in diblock copolymers with the Gaussian disphere
      model.
AB  - Pure melts of asymmetric diblock copolymers are studied by means of the off
      lattice Gaussian disphere model with Monte-Carlo kinetics. In this model, a
      diblock copolymer chain is mapped onto two soft repulsive spheres with
      fluctuating radii of gyration and distance between centers of mass of the
      spheres. Microscopic input quantities of the model such as the combined
      probability distribution for the radii of gyration and the distance between the
      spheres as well as conditional monomer number densities assigned to each block
      were derived in the previous work of F. Eurich and P. Maass [J. Chem. Phys. 114,
      7655 (2001)] within an underlying Gaussian chain model. The polymerization degree
      of the whole chain as well as those of the individual blocks are freely tunable
      parameters thus enabling a precise determination of the regions of stability of
      various phases. The model neglects entanglement effects which are irrelevant for
      the formation of ordered structures in diblock copolymers and which would
      otherwise unnecessarily increase the equilibration time of the system. The gyroid
      phase was reproduced in between the cylindrical and lamellar phases in systems
      with box sizes being commensurate with the size of the unit cell of the gyroid
      morphology. The region of stability of the gyroid phase was studied in detail and
      found to be consistent with the prediction of the mean-field theory. Packing
      frustration was observed in the form of increased radii of gyration of both
      blocks of the chains located close to the gyroid nodes.

PMID- 21198007
TI  - Invited review article: A 10 mK scanning probe microscopy facility.
AB  - We describe the design, development and performance of a scanning probe
      microscopy (SPM) facility operating at a base temperature of 10 mK in magnetic
      fields up to 15 T. The microscope is cooled by a custom designed, fully ultra
      high vacuum (UHV) compatible dilution refrigerator (DR) and is capable of in situ
      tip and sample exchange. Subpicometer stability at the tip-sample junction is
      achieved through three independent vibration isolation stages and careful design
      of the dilution refrigerator. The system can be connected to, or disconnected
      from, a network of interconnected auxiliary UHV chambers, which include growth
      chambers for metal and semiconductor samples, a field-ion microscope for tip
      characterization, and a fully independent additional quick access low temperature
      scanning tunneling microscope (STM) and atomic force microscope (AFM) system. To
      characterize the system, we present the cooling performance of the DR,
      vibrational, tunneling current, and tip-sample displacement noise measurements.
      In addition, we show the spectral resolution capabilities with tunneling
      spectroscopy results obtained on an epitaxial graphene sample resolving the
      quantum Landau levels in a magnetic field, including the sublevels corresponding
      to the lifting of the electron spin and valley degeneracies.

PMID- 21198008
TI  - Development of a new photoelectron spectroscopy instrument combining an
      electrospray ion source and photoelectron imaging.
AB  - A new apparatus has been constructed that combines electrospray ionization with a
      quadrupole mass filter, hexapole ion trap, and velocity-map imaging. The purpose
      is to record photoelectron images of isolated chromophore anions. To demonstrate
      the capability of our instrument we have recorded the photodetachment spectra of
      isolated deprotonated phenol and indole anions. To our knowledge, this is the
      first time that the photodetachment energy of the deprotonated indole anion has
      been recorded.

PMID- 21198009
TI  - A twisted periscope arrangement for transporting elliptically polarized light
      without change in its polarization state.
AB  - The authors describe a dual-mirror 90(?) twisted periscope arrangement for
      transporting polarized light in air, wherein a general elliptic polarization
      state of the light is preserved at all wavelengths. It is experimentally
      demonstrated that in the wavelength range 400-1000 nm, this arrangement preserves
      the polarization state fairly well when using either metallic or dielectric
      mirrors.

PMID- 21198010
TI  - Portable fiber sensors based on surface-enhanced Raman scattering.
AB  - Two portable molecular sensing systems based on surface-enhanced Raman scattering
      (SERS) have been experimentally demonstrated using either a tip-coated multimode
      fiber (TCMMF) or a liquid core photonic crystal fiber (LCPCF) as the SERS probe.
      With Rhodamine 6G as a test molecule, the TCMMF-portable SERS system achieved 2-3
      times better sensitivity than direct sampling (focusing the laser light directly
      into the sample without the fiber probe), and a highly sensitive LCPCF-portable
      SERS system reached a sensitivity up to 59 times that of direct sampling,
      comparable to the sensitivity enhancement achieved using fiber probes in the
      bulky Renishaw system. These fiber SERS probes integrated with a portable Raman
      spectrometer provide a promising scheme for a compact and flexible molecular
      sensing system with high sensitivity and portability.

PMID- 21198011
TI  - Long distance fiber-optic displacement sensor based on fiber collimator.
AB  - A simple fiber-optic displacement sensor based on reflective intensity modulated
      technology is demonstrated using a fiber collimator. The sensing range is over 30
      cm, which is over 100 times that of the conventional fiber-optic displacement
      sensor based on the normal single-mode fiber. The measured data are fitted into
      linear equation very well and the values of R-square are more than 0.995. The
      sensitivity of the device achieves 0.426 dB/cm over the range of 5-30 cm. By
      applying the relative technique, the errors resulted from the fluctuation of
      light source and influences of environment are effectively eliminated, and the
      stability for wide range measurement can be improved. The simplicity of the
      design, high dynamic range, stability and the ease of the fabrication make it
      suitable for applications in industries.

PMID- 21198012
TI  - Real-time nonlinear correction of back-focal-plane detection in optical tweezers.
AB  - Photodiode based detection of laser trapped beads using forward scattered light
      is a frequently employed technique for position measurement. There is a nonlinear
      relationship between photodiode outputs and bead position but for small
      displacements linear approximation holds well. Traditionally, the nonlinearity is
      compensated by normalizing the photodiode's position signal with the intensity
      signal and then using a polynomial fit in the range where voltage to position
      mapping is one to one. In this article, this range is extended by using the
      intensity signal as an independent input along with the two position signals. A
      map from the input signals to the actual position values is obtained. This
      mapping is one-to-one for a larger range that results in an increased detection
      range. An artificial neural network that facilitates implementation is employed
      for this purpose. This scheme is implemented on a Field Programmable Gate Array
      based data acquisition and control hardware with closed loop bandwidth of 50 kHz.
      Detection of the order of 350 nm from the center of detection laser is
      demonstrated for a 500 nm diameter bead compared to 180 nm achieved by a
      polynomial fit.

PMID- 21198013
TI  - An efficient magneto-optical trap of metastable krypton atoms.
AB  - We report a magneto-optical trap of metastable krypton atoms with a trap loading
      rate of 3*10(11) atoms/s and a trap capture efficiency of 3*10(-5). The system
      starts with an atomic beam of metastable krypton produced in a liquid-nitrogen
      cooled, radio-frequency driven discharge. The metastable beam flux emerging from
      the discharge is 1.5*10(14) atoms/s/sr. The flux in the forward direction is
      enhanced by a factor of 156 with transverse laser cooling. The atoms are then
      slowed inside a Zeeman slower before captured by a magneto-optic trap. The trap
      efficiency can be further improved, possibly to the 10(-2) level, by gas
      recirculation. Such an atom trap is useful in trace analysis applications where
      available sample size is limited.

PMID- 21198014
TI  - Modulated 3D cross-correlation light scattering: improving turbid sample
      characterization.
AB  - Accurate characterization using static light scattering (SLS) and dynamic light
      scattering (DLS) methods mandates the measurement and analysis of singly
      scattered light. In turbid samples, the suppression of multiple scattering is
      therefore required to obtain meaningful results. One powerful technique for
      achieving this, known as 3D cross-correlation, uses two simultaneous light
      scattering experiments performed at the same scattering vector on the same sample
      volume in order to extract only the single scattering information common to both.
      Here we present a significant improvement to this method in which the two
      scattering experiments are temporally separated by modulating the incident laser
      beams and gating the detector outputs at frequencies exceeding the timescale of
      the system dynamics. This robust modulation scheme eliminates cross-talk between
      the two beam-detector pairs and leads to a fourfold improvement in the cross
      correlation intercept. We measure the dynamic and angular-dependent scattering
      intensity of turbid colloidal suspensions and exploit the improved signal quality
      of the modulated 3D cross-correlation DLS and SLS techniques.

PMID- 21198015
TI  - Experimental study of new laser-based alignment system at the KEK B-factory
      injector linear accelerator.
AB  - A new laser-based alignment system for the precise alignment of accelerator
      components along an ideal straight line at the KEK B-factory injector linear
      accelerator (linac) is under development. This system is strongly required in the
      next generation of B-factories for the stable acceleration of high-brightness
      electron and positron beams with high bunch charges and also for maintaining the
      stability of injection beams with high quality. A new laser optics for the
      generation of a so-called Airy beam has been developed for the laser-based
      alignment system. The laser propagation characteristics both in vacuum and at
      atmospheric pressure have been systematically investigated in an 82-m-long
      straight section of the injector linac. The laser-based alignment measurements
      based on the new laser optics have been carried out with a measurement resolution
      of +/-0.1 mm level by using an existing laser detection electronics. The
      horizontal and vertical displacements from a reference laser line measured using
      this system are in good agreement with those measured using a standard telescope
      based optical alignment technique. In this report, we describe the experimental
      study in detail along with the basic designs and the recent developments in the
      new laser-based alignment system.

PMID- 21198016
TI  - Single-shot microscopic electron imaging of intense femtosecond laser-produced
      plasmas.
AB  - A simple technique for single-shot microscopic electron imaging was demonstrated
      for the study of intense femtosecond laser-produced plasmas. Passed through a
      permanent magnet lens designed for 110-keV electrons, hot electrons emitted from
      the plasma produced by a single laser pulse of 0.8 mJ with intensity of 3 *
      10(16) W/cm(2) were successfully imaged. Analyzing this image, we found that
      electrons were emitted from an area of 3 MUm in diameter. At higher laser
      intensity of 10(18) W/cm(2), distinct structures were observed in and near the
      focal spot of the laser; that is, the electrons were emitted from several
      separate spots. These results show that laser-plasma electron imaging is
      promising for studying the interactions of femtosecond lasers with high-density
      plasmas.

PMID- 21198017
TI  - Detection of x-ray emission in a nanosecond discharge in air at atmospheric
      pressure.
AB  - Measurement of x-ray emission is an important parameter to investigate runaway
      behavior of fast electrons produced in nanosecond-pulse gas discharge. An online
      detection system of x rays is described in this paper, and the system consists of
      an x-ray detector with NaI (Tl) scintillator and photomultiplier tube, and an
      integrated multichannel analyzer. The system is responsible for detecting x-ray
      emission signal, processing the detected signals, and scaling the energy
      distribution. The calibration results show that every channel of the detection
      system represents a given x-ray energy and various x rays can be divided into
      different energy ranges between 10 and 130 keV. For a repetitive nanosecond-pulse
      breakdown between highly nonuniform gaps in open air, an energy distribution is
      obtained using the online detection system. It shows that the x-ray emission is a
      continuous spectrum and the x rays of above 60 keV dominate in the detected
      energy distribution.

PMID- 21198018
TI  - Flux and energy analysis of species in hollow cathode magnetron ionized physical
      vapor deposition of copper.
AB  - To meet the stringent requirements of interconnect metallization for sub-32 nm
      technologies, an unprecedented level of flux and energy control of film forming
      species has become necessary to further advance ionized physical vapor deposition
      technology. Such technology development mandates improvements in methods to
      quantify the metal ion fraction, the gas/metal ion ratio, and the associated ion
      energies in the total ion flux to the substrate. In this work, a novel method
      combining planar Langmuir probes, quartz crystal microbalance (QCM), and gridded
      energy analyzer (GEA) custom instrumentation is developed to estimate the plasma
      density and temperature as well as to measure the metal ion fraction and ion
      energy. The measurements were conducted in a Novellus Systems, Inc. Hollow
      Cathode Magnetron (HCM(TM)) physical vapor deposition source used for deposition
      of Cu seed layer for 65-130 nm technology nodes. The gridded energy analyzer was
      employed to measure ion flux and ion energy, which was compared to the collocated
      planar Langmuir probe data. The total ion-to-metal neutral ratio was determined
      by the QCM combined with GEA. The data collection technique and the corresponding
      analysis are discussed. The effect of concurrent resputtering during the
      deposition process on film thickness profile is also discussed.

PMID- 21198019
TI  - The rotating wall machine: a device to study ideal and resistive
      magnetohydrodynamic stability under variable boundary conditions.
AB  - The rotating wall machine, a basic plasma physics experimental facility, has been
      constructed to study the role of electromagnetic boundary conditions on current
      driven ideal and resistive magnetohydrodynamic instabilities, including
      differentially rotating conducting walls. The device, a screw pinch magnetic
      geometry with line-tied ends, is described. The plasma is generated by an array
      of 19 plasma guns that not only produce high density plasmas but can also be
      independently biased to allow spatial and temporal control of the current
      profile. The design and mechanical performance of the rotating wall as well as
      diagnostic capabilities and internal probes are discussed. Measurements from
      typical quiescent discharges show the plasma to be high beta
      (<=p>2MU(0)/B(z)(2)), flowing, and well collimated. Internal probe measurements
      show that the plasma current profile can be controlled by the plasma gun array.

PMID- 21198020
TI  - Stray light analysis for the Thomson scattering diagnostic of the ETE Tokamak.
AB  - Thomson scattering is a well-established diagnostic for measuring local electron
      temperature and density in fusion plasma, but this technique is particularly
      difficult to implement due to stray light that can easily mask the scattered
      signal from plasma. To mitigate this problem in the multipoint Thomson scattering
      system implemented at the ETE (Experimento Tokamak Esferico) a detailed stray
      light analysis was performed. The diagnostic system was simulated in ZEMAX
      software and scattering profiles of the mechanical parts were measured in the
      laboratory in order to have near realistic results. From simulation, it was
      possible to identify the main points that contribute to the stray signals and
      changes in the dump were implemented reducing the stray light signals up to 60
      times.

PMID- 21198021
TI  - Diamagnetic flux measurement in Aditya tokamak.
AB  - Measurements of diamagnetic flux in Aditya tokamak for different discharge
      conditions are reported for the first time. The measured diamagnetic flux in a
      typical discharge is less than 0.6 mWb and therefore it has required careful
      compensation for various kinds of pick-ups. The hardware and software
      compensations employed in this measurement are described. We introduce
      compensation of a pick-up due to plasma current of less than 20 kA in short
      duration discharges, in which plasma pressure gradient is supposed to be
      negligible. The flux measurement during radio frequency heating is also presented
      in order to validate compensation.

PMID- 21198022
TI  - Hard x-ray correlation analysis as a diagnostic tool for the measurement of
      magnetic turbulence in tokamaks.
AB  - A diagnostic has been developed for the measurement and characterization of the
      magnetic turbulence occurring in the core region of a tokamak. A specially
      shielded detector looking in the tangential direction has been employed to
      measure the thin target bremsstrahlung from the core plasma. The thick target
      bremsstrahlung from the limiter is also recorded at the same time. Auto- and
      cross-correlation analyses have been shown to yield, respectively, the
      stochasticity of the magnetic fluctuations in the core region and the consequent
      diffusion coefficient of the nonthermal electrons. The measured stochasticity
      bears a relationship with the diffusion coefficient. Data obtained from internal
      magnetic probes corroborate the above trend but the hard x-ray measurement data
      are shown to be more reliable than those obtained from magnetic probes.

PMID- 21198023
TI  - Development of a digital integrator for the KSTAR device.
AB  - The development of an integrator for magnetic diagnostics becomes more important
      as the pulse length of fusion devices gets longer and longer, especially for
      present-day superconducting fusion devices. A small offset in the signal can
      cause a significant drift in the integrator output for long pulse experiments. A
      lock-in amplifying digital integrator has been developed for Wendelstein 7-X (W7
      X). It succeeds in suppressing the drift to a low value but requires about 100 ms
      for data processing. To shorten the data processing time, a Field Programmable
      Gate Array (FPGA) built in the digitizer is utilized. Since there is no need to
      transfer the data to an external computer, the integration can be done in real
      time. The microprocessor built in the digitizer directly transfers the data
      integrated in the internal FPGA into the reflective memory installed in the same
      compact Peripheral Component Interconnect chassis. These features result in a
      very compact system design. The design and the preliminary results of the digital
      integrator will be presented.

PMID- 21198024
TI  - Design and implementation of a full profile sub-cm ruby laser based Thomson
      scattering system for MAST.
AB  - A major upgrade to the ruby Thomson scattering (TS) system has been designed and
      implemented on the Mega-ampere spherical tokamak (MAST). MAST is equipped with
      two TS systems, a Nd:YAG laser system and a ruby laser system. Apart from common
      collection optics each system provides independent measurements of the electron
      temperature and density profile. This paper focuses on the recent upgrades to the
      ruby TS system. The upgraded ruby TS system measures 512 points across the major
      radius of the MAST vessel. The ruby laser can deliver one 10 J 40 ns pulse at 1
      Hz or two 5 J pulses separated by 100-800 MUs. The Thomson scattered light is
      collected at F/15 over 1.4 m. This system can resolve small (7 mm) structures at
      200 points in both the electron temperature and density channels at high optical
      contrast; ~50% modulated transfer function. The system is fully automated for
      each MAST discharge and requires little adjustment. The estimated measurement
      error for a 7 mm radial point is <4% of T(e) and <3% of n(e) in the range of 40
      eV to 2 keV, for a density of n(e)=2*10(19) m(-3). The photon statistics at lower
      density can be increased by binning in the radial direction as desired. A new
      intensified CCD camera design allows the ruby TS system to take two snapshots
      separated with a minimum time of 230 MUs. This is exploited to measure two
      density and temperature profiles or to measure the plasma background light.

PMID- 21198025
TI  - Impurities removal by laser blow-off from in-vacuum optical surfaces on RFX-mod
      experiment.
AB  - An in situ window cleaning system by laser blow-off through optical fiber has
      been developed on the basis of a feasibility study previously presented. The beam
      generated by a Q-switched Nd:YAG laser is launched in a vacuum box into a high
      damage threshold optical fiber through a lens. The fiber output is focused on the
      impurities-coated surface of a vacuum window exposed to the plasma of the RFX-mod
      experiment, and it is remotely controlled with an xy motion system to scan the
      entire surface. We first investigate the energy density threshold necessary to
      ablate the deposited impurity substrate on removed dirty windows: above
      threshold, a single laser pulse recovers ~95% of the window transmission before
      its exposure to the plasma, while below it the efficiency of the cleaning process
      is too poor. The system so conceived was then used to clean the three collection
      windows of the Main Thomson scattering diagnostic on RFX-mod. We also present
      results obtained applying the same technique to the SiO-protected Al mirror used
      for the Z(eff) diagnostic: an energy threshold for efficient impurity removal
      without mirror damage is first identified, then ablation tests are executed and
      analyzed in terms of recovered reflectivity. The SIMS technique is used both with
      windows and mirror to study the composition of surfaces before and after the
      ablation.

PMID- 21198026
TI  - An alternative flat scanner and micropositioning method for scanning probe
      microscope.
AB  - An alternative flat scanner used for combining a scanning probe microscope with
      an inverted optical microscope is presented. The scanner has a novel structure
      basically consisting of eight identical piezoelectric tubes, metal flexure beams,
      and one sample mount. Because of the specially designed structure, the scanner is
      able to carry a sample of more than 120 g during imaging. By applying voltages of
      +/-150 V, scanning range of more than 30 MUm in three dimensions can be achieved.
      To improve the reliability of the stick-slip motion, a new method for sample
      micropositioning is proposed by applying a pulsed voltage to the piezotubes to
      produce a motion in the z-axis. Reliable translation of the sample has been thus
      accomplished with the step length from ~700 nm to 9 MUm over a range of several
      millimeters. A homemade scanning probe microscope-inverted optical microscope
      system based on the scanner is described. Experimental results obtained with the
      system are shown.

PMID- 21198027
TI  - Ferrule-top atomic force microscope.
AB  - Ferrule-top cantilevers are a new generation of all-optical miniaturized devices
      for utilization in liquids, harsh environments, and small volumes [G. Gruca et
      al., Meas. Sci. Technol. 21, 094033 (2010)]. They are obtained by carving the end
      of a ferruled fiber in the form of a mechanical beam. Light coupled from the
      opposite side of the fiber allows detection of cantilever deflections. In this
      paper, we demonstrate that ferrule-top cantilevers can be used to develop ultra
      compact AFMs for contact mode imaging in air and in liquids with sensitivity
      comparable to that of commercial AFMs. The probes do not require any alignment
      procedure and are easy to handle, favoring applications also outside research
      laboratories.

PMID- 21198028
TI  - Effect of tip shape on line edge roughness measurement based on atomic force
      microscopy.
AB  - Atomic force microscopy (AFM) is an important tool in line edge roughness (LER)
      measurements, where accuracy for line edge identification is influenced by the
      shape of the tip. In this article, the effect of tip shape on LER measurement
      based on AFM is studied theoretically. The formulas for calculating the distance
      between the measured and actual line edge of the sample are presented. The
      effects of the three kinds of tips with different shapes are experimentally
      compared for validation. Suggestions on how to reduce measuring error caused by
      tip shape are also given.

PMID- 21198029
TI  - Wavefield characterization of nearly diffraction-limited focused hard x-ray beam
      with size less than 10 nm.
AB  - In situ wavefront compensation is a promising method to realize a focus size of
      only a few nanometers for x-ray beams. However, precise compensation requires
      evaluation of the wavefront with an accuracy much shorter than the wavelength.
      Here, we characterized a one-dimensionally focused beam with a width of 7 nm at
      20 keV using a multilayer mirror. We demonstrate that the wavefront can be
      determined precisely from multiple intensity profiles measured around the
      beamwaist. We compare the phase profiles recovered from intensity profiles
      measured under the same mirror condition but with three different aperture sizes
      and find that the accuracy of phase retrieval is as small as lambda/12.

PMID- 21198031
TI  - The effect of exit beam phase aberrations on parallel beam coherent x-ray
      reconstructions.
AB  - Diffraction artifacts from imperfect x-ray windows near the sample are an
      important consideration in the design of coherent x-ray diffraction measurements.
      In this study, we used simulated and experimental diffraction patterns in two and
      three dimensions to explore the effect of phase imperfections in a beryllium
      window (such as a void or inclusion) on the convergence behavior of phasing
      algorithms and on the ultimate reconstruction. A predictive relationship between
      beam wavelength, sample size, and window position was derived to explain the
      dependence of reconstruction quality on beryllium defect size. Defects
      corresponding to this prediction cause the most damage to the sample exit wave
      and induce signature error oscillations during phasing that can be used as a
      fingerprint of experimental x-ray window artifacts. The relationship between x
      ray window imperfection size and coherent x-ray diffractive imaging
      reconstruction quality explored in this work can play an important role in
      designing high-resolution in situ coherent imaging instrumentation and will help
      interpret the phasing behavior of coherent diffraction measured in these in situ
      environments.

PMID- 21198030
TI  - Nanoscale potential measurements in liquid by frequency modulation atomic force
      microscopy.
AB  - We have developed a method for local potential measurements in liquid using
      frequency modulation atomic force microscopy. In this method, local potential is
      calculated from the first and second harmonic vibrations of a cantilever induced
      by applying an ac bias voltage between a tip and a sample. The use of an ac bias
      voltage with a relatively high frequency prevents uncontrolled electrochemical
      reactions and redistribution of ions and water. The nanoscale resolution of the
      method is demonstrated by imaging potential distribution of a dodecylamine thin
      film deposited on a graphite surface in 1 mM NaCl solution.

PMID- 21198032
TI  - Glass transitions in nanoscale heated volumes of thin polystyrene films.
AB  - Glass transitions in confined polystyrene films on a silicon substrate were
      studied using atomic force microscopy incorporating a thermal tip. Three
      dimensional spatial nanoconfinements were achieved by controlling size and
      boundary conditions of small heated volumes of polymer nanostrands drawn from the
      polymer surface with the thermal tip, using appropriate loads and temperatures at
      the tip-polymer contact. Finite element analysis was performed to model
      mechanical contact and thermal transport, including the effects of contact
      radius, film thickness, and load on temperature and pressure distributions in the
      confined volume at the contact. The glass transition temperature (T(g)) was
      measured by observing the softening of polymers with increasing temperature. The
      measured surface T(g) exhibited a strong size dependence, while the subsurface
      T(g) increased with decreasing the distance to the substrate. A large increase in
      the surface T(g) was observed when the radius of contact was reduced below about
      10 nm. The increase in the glass transition temperature at the surface was
      attributed to the presence of surface and line tension at the nanometer contact,
      while the enhanced T(g) near the substrate was attributed to the pinning effects
      that reduces the mobility of the polymer molecules in the film over several
      hundreds of nanometers away from the polymer-substrate interface.

PMID- 21198033
TI  - Microwave atomic force microscopy imaging for nanometer-scale electrical property
      characterization.
AB  - We introduce a new type of microscopy which is capable of investigating surface
      topography and electrical property of conductive and dielectric materials
      simultaneously on a nanometer scale. The microwave atomic force microscopy is a
      combination of the principles of the scanning probe microscope and the microwave
      measurement technique. As a result, under the noncontact AFM working conditions,
      we successfully generated a microwave image of a 200-nm Au film coating on a
      glass wafer substrate with a spatial resolution of 120 nm and a measured voltage
      difference of 19.2 mV between the two materials.

PMID- 21198034
TI  - Finite element analysis and design of cubic high-pressure anvils based on the
      principle of lateral support.
AB  - This article theoretically investigates the lateral support on cubic high
      pressure anvil using finite element analysis. The results show that to gain the
      same chamber pressure, the value of system oil pressure can be decreased by
      reducing the lateral support area and the anvils' lifetime is extended when the
      lateral support area grows. The optimal lateral support area to maximize anvils'
      lifetime is 27.96 cm(2). Furthermore, the chamber pressure will increase by about
      6.99% when the value of lateral support area reduces from 33.16 to 27.96 cm(2)
      under same hydraulic rams. Our simulation results have been verified by many high
      pressure synthesis experiments and illustrated by breakage of anvils.

PMID- 21198035
TI  - New sample cell configuration for wide-frequency dielectric spectroscopy: DC to
      radio frequencies.
AB  - A new configuration for the sample cell to be used in broadband dielectric
      spectroscopy is presented. A coaxial structure with a parallel plate capacitor
      (outward parallel plate cell: OPPC) has made it possible to extend the frequency
      range significantly in comparison with the frequency range of the conventional
      configuration. In the proposed configuration, stray inductance is significantly
      decreased; consequently, the upper bound of the frequency range is improved by
      two orders of magnitude from the upper limit of conventional parallel plate
      capacitor (1 MHz). Furthermore, the value of capacitance is kept high by using a
      parallel plate configuration. Therefore, the precision of the capacitance
      measurement in the lower frequency range remains sufficiently high. Finally, OPPC
      can cover a wide frequency range (100 Hz-1 GHz) with an appropriate admittance
      measuring apparatus such as an impedance or network analyzer. The OPPC and the
      conventional dielectric cell are compared by examining the frequency dependence
      of the complex permittivity for several polar liquids and polymeric films.

PMID- 21198036
TI  - Absorbance and fluorometric sensing with capillary wells microplates.
AB  - Detection and readout from small volume assays in microplates are a challenge.
      The capillary wells microplate approach [Ng et al., Appl. Phys. Lett. 93, 174105
      (2008)] offers strong advantages in small liquid volume management. An adapted
      design is described and shown here to be able to detect, in a nonimaging manner,
      fluorescence and absorbance assays minus the error often associated with meniscus
      forming at the air-liquid interface. The presence of bubbles in liquid samples
      residing in microplate wells can cause inaccuracies. Pipetting errors, if not
      adequately managed, can result in misleading data and wrong interpretations of
      assay results; particularly in the context of high throughput screening. We show
      that the adapted design is also able to detect for bubbles and pipetting errors
      during actual assay runs to ensure accuracy in screening.

PMID- 21198037
TI  - Compact cosmic ray detector for unattended atmospheric ionization monitoring.
AB  - Two vertical cosmic ray telescopes for atmospheric cosmic ray ionization event
      detection are compared. Counter A, designed for low power remote use, was
      deployed in the Welsh mountains; its event rate increased with altitude as
      expected from atmospheric cosmic ray absorption. Independently, Counter B's event
      rate was found to vary with incoming particle acceptance angle. Simultaneous co
      located comparison of both telescopes exposed to atmospheric ionization showed a
      linear relationship between their event rates.

PMID- 21198038
TI  - Nondestructive measurement and high-precision evaluation of the electrical
      conductivity of doped GaAs wafers using microwaves.
AB  - A nondestructive method for measuring the electrical conductivity of doped GaAs
      wafers using a compact microwave instrument is presented. Based on the
      characteristics of the microwave detector and the fact that the microwave
      measurement is independent of the thickness of the wafer, the analytical and
      explicit expressions to evaluate the electrical conductivity of the wafer are
      derived. Using this method, only the voltages of the reflected signals for two
      wafer samples whose conductivities are known are required to calibrate the two
      undetermined constants in the equation. Then, the conductivity of any other wafer
      can be evaluated by substituting the measured voltage of the reflected signal
      into the explicit expressions. Seven different doped GaAs wafers with thickness
      larger than 350 MUm and conductivities in the range of 1.3 * 10(4) S/m to 7.6 *
      10(4) S/m are measured in the experiment, two of which are used for calibration.
      The evaluated results agree well with those obtained by the conventional Hall
      effect measurement method, with an evaluation error less than +/-4.5%. The
      proposed method is potentially useful for the contactless and nondestructive
      evaluation of the electrical conductivity of any kind of semiconductor wafer.

PMID- 21198039
TI  - Ultra-low-noise preamplifier for condenser microphones.
AB  - The paper presents the design of a low-noise preamplifier dedicated for condenser
      measurement microphones used in high sensitivity applications, in which amplifier
      noise is the main factor limiting sensitivity of the measurements. In measurement
      microphone preamplifiers, the dominant source of noise at lower frequencies is
      the bias resistance of the input stage. In the presented solution, resistors were
      connected to the input stage by means of switches. The switches are opened during
      measurements, which disconnects the resistors from the input stage and results in
      noise reduction. Closing the switches allows for fast charging of the microphone
      capacitance. At low frequencies the noise of the designed preamplifier is a few
      times lower in comparison to similar, commercially available instruments.

PMID- 21198040
TI  - A high voltage pulse power supply for metal plasma immersion ion implantation and
      deposition.
AB  - We describe the design and implementation of a high voltage pulse power supply
      (pulser) that supports the operation of a repetitively pulsed filtered vacuum arc
      plasma deposition facility in plasma immersion ion implantation and deposition
      (Mepiiid) mode. Negative pulses (micropulses) of up to 20 kV in magnitude and 20
      A peak current are provided in gated pulse packets (macropulses) over a broad
      range of possible pulse width and duty cycle. Application of the system
      consisting of filtered vacuum arc and high voltage pulser is demonstrated by
      forming diamond-like carbon (DLC) thin films with and without substrate bias
      provided by the pulser. Significantly enhanced film/substrate adhesion is
      observed when the pulser is used to induce interface mixing between the DLC film
      and the underlying Si substrate.

PMID- 21198041
TI  - Signal-to-noise analysis of biomedical photoacoustic measurements in time and
      frequency domains.
AB  - Sensitivity analysis of photoacoustic measurements is conducted using estimates
      of the signal-to-noise ratio (SNR) achieved under two different modes of optical
      excitation. The standard pulsed time-domain photoacoustic imaging is compared to
      the frequency-domain counterpart with a modulated optical source. The feasibility
      of high-SNR continuous wave depth-resolved photoacoustics with frequency-swept
      (chirp) modulation pattern has been demonstrated. Utilization of chirped
      modulation waveforms achieves dramatic SNR increase of the periodic signals and
      preserves axial resolution comparable to the time-domain method. Estimates of the
      signal-to-noise ratio were obtained using typical parameters of piezoelectric
      transducers and optical properties of tissue.

PMID- 21198042
TI  - Measurement of thermal properties of thin films up to high temperatures--pulsed
      photothermal radiometry system and Si-B-C-N films.
AB  - A new arrangement of two-detector pulsed photothermal radiometry measurement
      system has been developed enabling temperature dependence measurement of thermal
      properties of thin films up to high temperatures. Only a few methods are
      available in this temperature range for thin films' thermal properties
      investigation, but there is a need for their knowledge in the fields of high
      temperature electronics and high-speed machining. The present system enables
      simultaneous determination of the thin film effusivity, thermal conductivity, and
      volumetric specific heat in the temperature range from room temperature to 600 
      degrees C. The samples are placed in a vacuum chamber. The temperatures in the
      system were verified by an independent measurement and the system was tested on
      known bulk samples. Advantages and shortcomings of the method when used at higher
      temperatures and in the vacuum are described and discussed. Furthermore, Si-B-C-N
      thin films were studied. These amorphous ceramic materials possess an interesting
      set of mechanical and thermal properties. In particular, the films of the
      investigated chemical composition exhibit an excellent thermal stability at
      temperatures of up to 1700  degrees C. In the studied temperature range, from 20
      to 600  degrees C, the thermal conductivity increased with increasing temperature
      from 1.72 to 1.89 W m(-1) K(-1) and volumetric specific heat increased from 2.65
      to 3.76 * 10(6) J  m(-3) K(-1).

PMID- 21198043
TI  - Two-color optical charge-coupled-device-based pyrometer using a two-peak filter.
AB  - A two-color optical charge-coupled-device (CCD)-based pyrometer was developed
      using a multipeak interference filter with a color CCD sensor to measure
      multicolor signals with specified wavelengths. The effective and simple method
      adjusts the fixed spectrum response characteristics of a color CCD to allow
      improved temperature measurements. This pyrometer system not only has the
      advantage of traditional two-color (two-wavelength) pyrometry, but also overcomes
      the restrictions of color CCDs that can only be applied in waveband measurements.
      The measurement performance of the system using a two-peak filter (lambda(1)=643
      nm, lambda(2)=564 nm) was evaluated by blackbody experiments. The results show
      that the low temperature detection limit is increased about 200 K with an
      increase in the sensitivity of the measured signals compared with the original
      system without two-peak filter [Fu, et al., Opt. Laser Technol. 42, 586 (2010)].
      And the effective temperature range is also increased when T > 1233 K. The
      measured ratio C(R)/C(G) is monotonically relative to the temperature, which
      simplifies the measurements. The temperature sensitivity of 2.49 is larger and
      more uniform than the temperature sensitivity of 1.36 in the previous original
      system. Thus, the measurement performance of the new system is greatly improved.
      Finally, as an application, the surface temperature distribution of stainless
      steel sample in hot environments was determined by this new CCD-based pyrometer.
      The results agree well with the spectrometer-based results and further verify the
      applicability of the new system.

PMID- 21198044
TI  - Curie point, susceptibility, and temperature measurements of rapidly heated
      ferromagnetic wires.
AB  - This article describes a technique to measure the temperature of a resistively
      heated ferromagnetic wire. The wire's temperature rapidly increases, a scenario
      in which a thermocouple or thermistor's thermal inertia prevents it from keeping
      up with the rapid temperature variation. The temperature is derived from
      electrical measurands (voltage and current) and time, as well as thermophysical
      data such as heat losses and emissivity, and is based on a dynamical thermal
      electrical energy conservation principle. We go on to use our technique for the
      quantitative determination of the Curie point as well as the magnetic
      susceptibility at elevated temperatures. The results are in good agreement with
      accepted values.

PMID- 21198045
TI  - Two-dimensional higher order noise spectroscopy up to radio frequencies.
AB  - Going beyond the usual determination of the frequency-resolved power spectrum of
      an electrical noise signal, we implement a setup for the determination of a
      frequency-resolved two-dimensional correlation spectrum. We demonstrate
      measurements of two-dimensional correlation spectra with sampling rates up to 180
      MSamples/s and real-time numerical evaluation with up to 100% data coverage. As
      an example, the purely Gaussian behavior of 1/f resistor noise is demonstrated
      with unprecedented sensitivity by verifying the absence of correlations between
      different frequencies. Unlike the usual power spectrum, the correlation spectrum
      is shown to contain information on both the homogeneous and inhomogeneous
      linewidths of a signal, suggesting applications in spin noise spectroscopy and
      signal analysis in general.

PMID- 21198046
TI  - An integrated instrument for rapidly deforming living cells using rapid pressure
      pulses and simultaneously monitoring applied strain in near real time.
AB  - Because many types of living cells are sensitive to applied strain, different in
      vitro models have been designed to elucidate the cellular and subcellular
      processes that respond to mechanical deformation at both the cell and tissue
      level. Our focus was to improve upon an already established strain system to make
      it capable of independently monitoring the deflection and applied pressure
      delivered to specific wells of a commercially available, deformable multiwell
      culture plate. To accomplish this, we devised a custom frame that was capable of
      mounting deformable 6 or 24 well plates, a pressurization system that could load
      wells within the plates, and a camera-based imaging system which was capable of
      capturing strain responses at a sufficiently high frame rate. The system used a
      user defined program constructed in Labview((r)) to trigger plate pressurization
      while simultaneously allowing the deflection of the silicone elastomeric plate
      bottoms to be imaged in near real time. With this system, up to six wells could
      be pulsed simultaneously using compressed air or nitrogen. Digital image capture
      allowed near-real time monitoring of applied strain, strain rate, and the cell
      loading profiles. Although our ultimate goal is to determine how different strain
      rates applied to neurons modulates their intrinsic biochemical cascades, the same
      platform technology could be readily applied to other systems. Combining
      commercially available, deformable multiwell plates with a simple instrument
      having the monitoring capabilities described here should permit near real time
      calculations of stretch-induced membrane strain in multiple wells in real time
      for a wide variety of applications, including high throughput drug screening.

PMID- 21198047
TI  - Temperature-stable parallel-plate dielectric cell for broadband liquid impedance
      measurements.
AB  - A liquid impedance cell for broadband impedance measurements up to 110 MHz is
      presented. The design incorporates temperature control and minimizes parasitic
      capacitance and inductance. The cell is simple to fabricate and uses chemically
      resistant materials, stainless steel, and Teflon. This dielectric cell can be
      used in a variety of liquid measurements, particularly those related to impedance
      measurements of biological objects in solution. Temperature control is
      illustrated in measurements of the permittivity of deionized water from 5 to 55  
      degrees C. Numerical fitting procedures employed on the relaxation curves
      indicate good agreement with previous studies on beta-lactoglobulin and hen
      lysozyme. Titration capability is demonstrated through dielectric titration of
      hen lysozyme and beta-lactoglobulin.

PMID- 21198048
TI  - Characterization of a fast gas analyzer based on Raman scattering for the
      analysis of synthesis gas.
AB  - A sensor system for fast analysis of synthesis gas (mixtures of CO and H(2)) is
      proposed and characterized. The system is based on spontaneous Raman scattering,
      which enables simultaneous concentration measurements of all relevant species.
      For typical synthesis gas applications, this system has to face large variations
      of temperature and pressure. In addition, strong fluctuations in mixture
      composition may occur, which lead to rather inconvenient signal intensities. In
      this paper, we describe a low resolution spectrometer designed to function as a
      synthesis gas sensor and characterize pressure and temperature effects on
      concentration measurements. In addition, the use of different spectral ranges and
      calibration strategies is investigated in view of measurement accuracy and
      precision.

PMID- 21198049
TI  - A high-pressure cell for kinetic studies on gas hydrates by powder x-ray
      diffraction.
AB  - A new high-pressure-low-temperature cell was developed for in situ observations
      of gas hydrates by powder x-ray diffraction. The experimental setup allows
      investigating hydrate formation and dissociation as well as transformation
      processes between different hydrate crystal structures as a function of pressure,
      temperature, and feed gas composition. Due to a continuous gas flow, the
      composition of the gas phase is kept constant during the whole experiment. This
      is crucial for the formation of mixed hydrates formed from feed gas mixtures that
      contain one or more components in low concentrations. The pressure cell can be
      used in a pressure range between 0.1 and 4.0 MPa and a temperature range between
      248 and 298 K. First results of time-resolved measurements of a mixed structure
      II CH(4) + iso-C(4)H(10) hydrate and a structure I CO(2) hydrate are presented.

PMID- 21198050
TI  - Minimizing crosstalk in three-axial induction magnetometers.
AB  - A model for crosstalk in three-axial induction magnetometers has been developed
      theoretically and verified experimentally. The effect of crosstalk on the
      magnetometer accuracy has been analyzed. It has been found that the inevitable
      crosstalk in the transverse coils has two components: one due to the applied
      magnetic flux and the other due to the secondary flux produced by the electric
      current in the longitudinal coil. The first component has a constant magnitude.
      The phase of the second component, relative to the first one, is nearly 180
      degrees  at low frequencies, 90 degrees  at resonance, and 0 degrees  at high
      frequencies. Its magnitude approaches zero at low frequencies, has the maximum at
      resonance, and then drops off by a factor equal to the coils' quality factor and
      approaches the first component value. As a result, the crosstalk due to the
      applied flux is dominant at low frequencies. At a frequency just below the
      resonance, the crosstalk is very low, if no magnetic feedback is applied. Just
      above the resonance, the crosstalk reaches the maximum because of the rapid
      increase in the secondary flux. Applying a strong enough magnetic feedback nearly
      flattens the crosstalk amplitude response. However, an undesirable effect of the
      feedback is that it significantly increases the minimum crosstalk value. A very
      low crosstalk at a single frequency can be beneficial for magnetometers tuned to
      a narrow frequency band. It can also be beneficial for wide-band magnetometers to
      measure their mechanical orthogonality with a minimum effect of crosstalk.

PMID- 21198051
TI  - New large volume hydrothermal reaction cell for studying chemical processes under
      supercritical hydrothermal conditions using time-resolved in situ neutron
      diffraction.
AB  - The design and testing of a new large volume Inconel pressure cell for the in
      situ study of supercritical hydrothermal syntheses using time-resolved neutron
      diffraction is introduced for the first time. The commissioning of this new cell
      is demonstrated by the measurement of the time-of-flight neutron diffraction
      pattern for TiO(2) (Anatase) in supercritical D(2)O on the POLARIS diffractometer
      at the United Kingdom's pulsed spallation neutron source, ISIS, Rutherford
      Appleton Laboratory. The sample can be studied over a wide range of temperatures
      (25-450  degrees C) and pressures (1-355 bar). This novel apparatus will now
      enable us to study the kinetics and mechanisms of chemical syntheses under
      extreme environments such as supercritical water, and in particular to study the
      crystallization of a variety of technologically important inorganic materials.

PMID- 21198052
TI  - Expression of picogram sensitive bending modes in piezoelectric cantilever
      sensors with nonuniform electric fields generated by asymmetric electrodes.
AB  - Single-layer uniform cross-sectioned piezoelectric macro-cantilevers fabricated
      with an asymmetric electrode configuration enabled electrical measurement of
      picogram-sensitive resonant bending modes in liquids. Bending modes were
      otherwise not electrically measurable without excitation by a nonuniform electric
      field created by the geometric asymmetry in electrode design used. Electrode
      modification was confirmed by energy-dispersive X-ray spectroscopy (EDS). Mass
      change sensitivity was tested using both bulk density changes and surface
      chemisorption experiments in a continuous flow apparatus. Significant response to
      density changes as small as 0.004 g/mL was measured. A sensitivity limit of ~1
      picogram in liquid was determined from 1-dodecanethiol chemisorption experiments.
      The sensitivity decreased with chemisorbed mass and was log-linear over five
      orders of magnitude. The observed resonance responses were in agreement with
      previously reported models of resonating cantilever sensors. This work
      demonstrates experimentally for the first time that introducing electrode
      asymmetry enables measurement of bending modes in cantilevers containing only a
      single piezoelectric layer.

PMID- 21198053
TI  - High throughput optical readout of dense arrays of nanomechanical systems for
      sensing applications.
AB  - We present an instrument based on the scanning of a laser beam and the
      measurement of the reflected beam deflection that enables the readout of arrays
      of nanomechanical systems without limitation in the geometry of the sample, with
      high sensitivity and a spatial resolution of few micrometers. The measurement of
      nanoscale deformations on surfaces of cm(2) is performed automatically, with
      minimal need of user intervention for optical alignment. To exploit the
      capability of the instrument for high throughput biological and chemical sensing,
      we have designed and fabricated a two-dimensional array of 128 cantilevers. As a
      proof of concept, we measure the nanometer-scale bending of the 128 cantilevers,
      previously coated with a thin gold layer, induced by the adsorption and self
      assembly on the gold surface of several self-assembled monolayers. The instrument
      is able to provide the static and dynamic responses of cantilevers with
      subnanometer resolution and at a rate of up to ten cantilevers per second. The
      instrumentation and the fabricated chip enable applications for the analysis of
      complex biological systems and for artificial olfaction.

PMID- 21198054
TI  - Portable laser speckle perfusion imaging system based on digital signal
      processor.
AB  - The ability to monitor blood flow in vivo is of major importance in clinical
      diagnosis and in basic researches of life science. As a noninvasive full-field
      technique without the need of scanning, laser speckle contrast imaging (LSCI) is
      widely used to study blood flow with high spatial and temporal resolution.
      Current LSCI systems are based on personal computers for image processing with
      large size, which potentially limit the widespread clinical utility. The need for
      portable laser speckle contrast imaging system that does not compromise
      processing efficiency is crucial in clinical diagnosis. However, the processing
      of laser speckle contrast images is time-consuming due to the heavy calculation
      for enormous high-resolution image data. To address this problem, a portable
      laser speckle perfusion imaging system based on digital signal processor (DSP)
      and the algorithm which is suitable for DSP is described. With highly integrated
      DSP and the algorithm, we have markedly reduced the size and weight of the system
      as well as its energy consumption while preserving the high processing speed. In
      vivo experiments demonstrate that our portable laser speckle perfusion imaging
      system can obtain blood flow images at 25 frames per second with the resolution
      of 640 * 480 pixels. The portable and lightweight features make it capable of
      being adapted to a wide variety of application areas such as research laboratory,
      operating room, ambulance, and even disaster site.

PMID- 21198055
TI  - Transfer-matrix-based method for an analytical description of velocity-map
      imaging spectrometers.
AB  - We propose a simple and general analytical model describing the operation of a
      velocity-map-imaging spectrometer. We show that such a spectrometer, possibly
      equipped with a magnifying lens, can be efficiently modeled by combining
      analytical expressions for the axial potential distributions along with a
      transfer matrix method. The model leads transparently to the prediction of the
      instrument's operating conditions as well as to its resolution. A photoelectron
      velocity-map-imaging spectrometer with a magnifying lens, built and operated
      along the lines suggested by the model has been successfully employed for
      recording images at threshold photoionization of atomic lithium. The model's
      reliability is demonstrated by the fairly good agreement between experimental
      results and calculations. Finally, the limitations of the analytical method along
      with possible generalizations, extensions, and potential applications are also
      discussed. The model may serve as a guide for users interested in building and
      operating such spectrometers as well as a tutorial tool.

PMID- 21198056
TI  - Note: Direct sensor resistance-to-frequency conversion with generalized impedance
      converter.
AB  - In this note a squared output signal is generated from an astable circuit. Its
      frequency has a linear dependence on the resistance value of a resistive
      temperature sensor. The main circuit to obtain this direct relationship is the
      generalized impedance converter configured as a capacitor controlled by a sensor
      resistance. The proposed measurement method allows a direct analog-to-digital
      interface of information involved in resistive sensors. The converter finds
      applications in portable low voltage and low power design of instrumentation
      electronic systems.

PMID- 21198057
TI  - Note: Autonomous pulsed power generator based on transverse shock wave
      depolarization of ferroelectric ceramics.
AB  - Autonomous pulsed generators utilizing transverse shock wave depolarization
      (shock front propagates across the polarization vector P(0)) of
      Pb(Zr(0.52)Ti(0.48))O(3) poled piezoelectric ceramics were designed, constructed,
      and experimentally tested. It was demonstrated that generators having total
      volume of 50 cm(3) were capable of producing the output voltage pulses with
      amplitude up to 43 kV with pulse duration 4 MUs. A comparison of high-voltage
      operation of transverse and longitudinal shock wave ferroelectric generators is
      given.

PMID- 21198058
TI  - Note: A table-top blast driven shock tube.
AB  - The prevalence of blast-induced traumatic brain injury in conflicts in Iraq and
      Afghanistan has motivated laboratory scale experiments on biomedical effects of
      blast waves and studies of blast wave transmission properties of various
      materials in hopes of improving armor design to mitigate these injuries. This
      paper describes the design and performance of a table-top shock tube that is more
      convenient and widely accessible than traditional compression driven and blast
      driven shock tubes. The design is simple: it is an explosive driven shock tube
      employing a rifle primer that explodes when impacted by the firing pin. The
      firearm barrel acts as the shock tube, and the shock wave emerges from the
      muzzle. The small size of this shock tube can facilitate localized application of
      a blast wave to a subject, tissue, or material under test.

PMID- 21198059
TI  - Note: Zeeman splitting measurements in a high-temperature plasma.
AB  - The Zeeman effect has been used for measurement of magnetic fields in low
      temperature plasma, but the diagnostic technique is difficult to implement in a
      high-temperature plasma. This paper describes new instrumentation and methodology
      for simultaneous measurement of the entire Doppler-broadened left and right
      circularly polarized Zeeman spectra in high-temperature plasmas. Measurements are
      made using spectra emitted parallel to the magnetic field by carbon impurities in
      high-temperature plasma. The Doppler-broadened width is much larger than the
      magnitude of the Zeeman splitting, thus simultaneous recording of the two
      circularly polarized Zeeman line profiles is key to accurate measurement of the
      magnetic field in the ZaP Z-pinch plasma device. Spectral data are collected
      along multiple chords on both sides of the symmetry axis of the plasma. This
      enables determination of the location of the current axis of the Z-pinch and of
      lower-bound estimates of the local magnetic field at specific radial locations in
      the plasma.

PMID- 21198063
TI  - Patterns in a suspension contained in a horizontally rotating cylinder.

PMID- 21198064
TI  - Faraday instability on a network.

PMID- 21198065
TI  - Inviscid simulations of interacting flags.

PMID- 21198066
TI  - Follow the bouncing balls! Three-dimensional imaging of flowing granular
      suspensions.

PMID- 21198068
TI  - Statistics of the general circulation from cumulant expansions.

PMID- 21198067
TI  - Scale-local velocity fields from particle-tracking data.

PMID- 21198070
TI  - The Lagrangian picture of heat transfer in convective turbulence.

PMID- 21198069
TI  - Communities in multislice voting networks.

PMID- 21198071
TI  - Competition for popularity in bipartite networks.
AB  - We present a dynamical model for rewiring and attachment in bipartite networks.
      Edges are placed between nodes that belong to catalogs that can either be fixed
      in size or growing in size. The model is motivated by an empirical study of data
      from the video rental service Netflix, which invites its users to give ratings to
      the videos available in its catalog. We find that the distribution of the number
      of ratings given by users and that of the number of ratings received by videos
      both follow a power law with an exponential cutoff. We also examine the activity
      patterns of Netflix users and find bursts of intense video-rating activity
      followed by long periods of inactivity. We derive ordinary differential equations
      to model the acquisition of edges by the nodes over time and obtain the
      corresponding time-dependent degree distributions. We then compare our results
      with the Netflix data and find good agreement. We conclude with a discussion of
      how catalog models can be used to study systems in which agents are forced to
      choose, rate, or prioritize their interactions from a large set of options.

PMID- 21198072
TI  - Perturbation series for calculation of invariant surface splitting in volume
      preserving maps.
AB  - The invariant surface splittings for small perturbation are described for two
      dimensional and three-dimensional sample volume-preserving maps by explicit
      analytic expressions obtained from perturbation series for the self-adjoint
      operator related to the Frobenius-Perron operator.

PMID- 21198073
TI  - Motion of vortices outside a cylinder.
AB  - The problem of motion of the vortices around an oscillating cylinder in the
      presence of a uniform flow is considered. The Hamiltonian for vortex motion for
      the case with no uniform flow and stationary cylinder is constructed, reduced,
      and constant Hamiltonian (energy) curves are plotted when the system is shown to
      be integrable according to Liouville. By adding uniform flow to the system and by
      allowing the cylinder to vibrate, we model the natural vibration of the cylinder
      in the flow field, which has applications in ocean engineering involving tethers
      or pipelines in a flow field. We conclude that in the chaotic case forces on the
      cylinder may be considerably larger than those on the integrable case depending
      on the initial positions of vortices and that complex phenomena such as chaotic
      capture and escape occur when the initial positions lie in a certain region.

PMID- 21198074
TI  - Hyperbolic chaos in the klystron-type microwave vacuum tube oscillator.
AB  - The ring-loop oscillator consisting of two coupled klystrons which is capable of
      generating hyperbolic chaotic signal in the microwave band is considered. The
      system of delayed-differential equations describing the dynamics of the
      oscillator is derived. This system is further reduced to the two-dimensional
      return map under the assumption of the instantaneous build-up of oscillations in
      the cavities. The results of detailed numerical simulation for both models are
      presented showing that there exists large enough range of control parameters
      where the sustained regime corresponds to the structurally stable hyperbolic
      chaos.

PMID- 21198075
TI  - Extensive chaos in the Lorenz-96 model.
AB  - We explore the high-dimensional chaotic dynamics of the Lorenz-96 model by
      computing the variation of the fractal dimension with system parameters. The
      Lorenz-96 model is a continuous in time and discrete in space model first
      proposed by Lorenz to study fundamental issues regarding the forecasting of
      spatially extended chaotic systems such as the atmosphere. First, we explore the
      spatiotemporal chaos limit by increasing the system size while holding the
      magnitude of the external forcing constant. Second, we explore the strong driving
      limit by increasing the external forcing while holding the system size fixed. As
      the system size is increased for small values of the forcing we find dynamical
      states that alternate between periodic and chaotic dynamics. The windows of chaos
      are extensive, on average, with relative deviations from extensivity on the order
      of 20%. For intermediate values of the forcing we find chaotic dynamics for all
      system sizes past a critical value. The fractal dimension exhibits a maximum
      deviation from extensivity on the order of 5% for small changes in system size
      and the deviation from extensivity decreases nonmonotonically with increasing
      system size. The length scale describing the deviations from extensivity is
      consistent with the natural chaotic length scale in support of the suggestion
      that deviations from extensivity are due to the addition of chaotic degrees of
      freedom as the system size is increased. We find that each wavelength of the
      deviation from extensive chaos contains on the order of two chaotic degrees of
      freedom. As the forcing is increased, at constant system size, the dimension
      density grows monotonically and saturates at a value less than unity. We use this
      to quantify the decreasing size of chaotic degrees of freedom with increased
      forcing which we compare with spatial features of the patterns.

PMID- 21198076
TI  - Interactions between oscillatory modes near a 2:3 resonant Hopf-Hopf bifurcation.
AB  - In this paper, the dynamics near a 2:3 resonant Hopf-Hopf bifurcation is studied.
      The main result is the identification of a distinctive structure connecting 1:2
      and 1:3 strong resonances of limit cycles. This structure is found near the Hopf
      Hopf point revealing that it may be associated to the resonant case, and may
      provide useful information about the dynamics generated by this codimension 3
      bifurcation.

PMID- 21198077
TI  - Stochastic solutions of Navier-Stokes equations: an experimental evidence.
AB  - An electrodynamic loudspeaker has been operated in anharmonic regime indicated by
      the nonlinear ordinary differential equation when spring constant gamma in
      restoring term, as well as, viscoelasticity of the membrane material, increases
      with displacement. For driving currents in the range of 2.8-3.3 A, doubling of
      the vibration period appears, while for currents in the range of 3.3-3.6 A,
      multiple sequences of subharmonic vibrations begin with f/4 and 3f/4. An
      application of currents higher than 3.6 A results in a spectrum, characteristic
      for the chaotic state. The loudspeaker was then operated in a closed chamber, and
      subharmonic vibrations disappeared by an evacuation. Subsequent injection of air
      revoked them again at ~ 120 mbar (Re(')=476) when air viscous forces dominate the
      Morse convection. At 430 mbar (Re=538) single vibration state was restored, and
      the phenomenon is in an agreement with prediction of the five mode truncation
      procedure applied to the Navier-Stokes equations describing a two-dimensional
      incompressible fluid.

PMID- 21198078
TI  - Synchronization of an ensemble of oscillators regulated by their spatial
      movement.
AB  - Synchronization for a collection of oscillators residing in a finite two
      dimensional plane is explored. The coupling between any two oscillators in this
      array is unidirectional, viz., master-slave configuration. Initially the
      oscillators are distributed randomly in space and their autonomous time-periods
      follow a Gaussian distribution. The duty cycles of these oscillators, which work
      under an on-off scenario, are normally distributed as well. It is realized that
      random hopping of oscillators is a necessary condition for observing global
      synchronization in this ensemble of oscillators. Global synchronization in the
      context of the present work is defined as the state in which all the oscillators
      are rendered identical. Furthermore, there exists an optimal amplitude of random
      hopping for which the attainment of this global synchronization is the fastest.
      The present work is deemed to be of relevance to the synchronization phenomena
      exhibited by pulse coupled oscillators such as a collection of fireflies.

PMID- 21198079
TI  - Phase synchronization between collective rhythms of globally coupled oscillator
      groups: noisy identical case.
AB  - We theoretically investigate the collective phase synchronization between
      interacting groups of globally coupled noisy identical phase oscillators
      exhibiting macroscopic rhythms. Using the phase reduction method, we derive
      coupled collective phase equations describing the macroscopic rhythms of the
      groups from microscopic Langevin phase equations of the individual oscillators
      via nonlinear Fokker-Planck equations. For sinusoidal microscopic coupling, we
      determine the type of the collective phase coupling function, i.e., whether the
      groups exhibit in-phase or antiphase synchronization. We show that the
      macroscopic rhythms can exhibit effective antiphase synchronization even if the
      microscopic phase coupling between the groups is in-phase, and vice versa.
      Moreover, near the onset of collective oscillations, we analytically obtain the
      collective phase coupling function using center-manifold and phase reductions of
      the nonlinear Fokker-Planck equations.

PMID- 21198080
TI  - Phase synchronization between collective rhythms of globally coupled oscillator
      groups: noiseless nonidentical case.
AB  - We theoretically study the synchronization between collective oscillations
      exhibited by two weakly interacting groups of nonidentical phase oscillators with
      internal and external global sinusoidal couplings of the groups. Coupled
      amplitude equations describing the collective oscillations of the oscillator
      groups are obtained by using the Ott-Antonsen ansatz, and then coupled phase
      equations for the collective oscillations are derived by phase reduction of the
      amplitude equations. The collective phase coupling function, which determines the
      dynamics of macroscopic phase differences between the groups, is calculated
      analytically. We demonstrate that the groups can exhibit effective antiphase
      collective synchronization even if the microscopic external coupling between
      individual oscillator pairs belonging to different groups is in-phase, and
      similarly effective in-phase collective synchronization in spite of microscopic
      antiphase external coupling between the groups.

PMID- 21198081
TI  - On the role of frustration in excitable systems.
AB  - We study the role of frustration in excitable systems that allow for oscillations
      either by construction or in an induced way. We first generalize the notion of
      frustration to systems whose dynamical equations do not derive from a
      Hamiltonian. Their couplings can be directed or undirected; they should come in
      pairs of opposing effects like attractive and repulsive, or activating and
      repressive, ferromagnetic and antiferromagnetic. As examples we then consider
      bistable frustrated units as elementary building blocks of our motifs of coupled
      units. Frustration can be implemented in these systems in various ways: on the
      level of a single unit via the coupling of a self-loop of positive feedback to a
      negative feedback loop, on the level of coupled units via the topology or via the
      type of coupling which may be repressive or activating. In comparison to systems
      without frustration, we analyze the impact of frustration on the type and number
      of attractors and observe a considerable enrichment of phase space, ranging from
      stable fixed-point behavior over different patterns of coexisting options for
      phase-locked motion to chaotic behavior. In particular we find multistable
      behavior even for the smallest motifs as long as they are frustrated. Therefore
      we confirm an enrichment of phase space here for excitable systems with their
      many applications in biological systems, a phenomenon that is familiar from
      frustrated spin systems and less known from frustrated phase oscillators. So the
      enrichment of phase space seems to be a generic effect of frustration in
      dynamical systems. For a certain range of parameters our systems may be realized
      in cell tissues. Our results point therefore on a possible generic origin for
      dynamical behavior that is flexible and functionally stable at the same time,
      since frustrated systems provide alternative paths for the same set of parameters
      and at the same "energy costs."

PMID- 21198082
TI  - Impact of degree heterogeneity on the behavior of trapping in Koch networks.
AB  - Previous work shows that the mean first-passage time (MFPT) for random walks to a
      given hub node (node with maximum degree) in uncorrelated random scale-free
      networks is closely related to the exponent gamma of power-law degree
      distribution P(k) ~ k(-gamma), which describes the extent of heterogeneity of
      scale-free network structure. However, extensive empirical research indicates
      that real networked systems also display ubiquitous degree correlations. In this
      paper, we address the trapping issue on the Koch networks, which is a special
      random walk with one trap fixed at a hub node. The Koch networks are power-law
      with the characteristic exponent gamma in the range between 2 and 3, they are
      either assortative or disassortative. We calculate exactly the MFPT that is the
      average of first-passage time from all other nodes to the trap. The obtained
      explicit solution shows that in large networks the MFPT varies lineally with node
      number N, which is obviously independent of gamma and is sharp contrast to the
      scaling behavior of MFPT observed for uncorrelated random scale-free networks,
      where gamma influences qualitatively the MFPT of trapping problem.

PMID- 21198083
TI  - Fundamental solitons in discrete lattices with a delayed nonlinear response.
AB  - The formation of unstaggered localized modes in dynamical lattices can be
      supported by the interplay of discreteness and nonlinearity with a finite
      relaxation time. In rapidly responding nonlinear media, on-site discrete solitons
      are stable, and their broad intersite counterparts are marginally stable,
      featuring a virtually vanishing real instability eigenvalue. The solitons become
      unstable in the case of the slowly relaxing nonlinearity. The character of the
      instability alters with the increase of the delay time, which leads to a change
      in the dynamics of unstable discrete solitons. They form robust localized
      breathers in rapidly relaxing media, and decay into oscillatory diffractive
      pattern in the lattices with a slow nonlinear response. Marginally stable
      solitons can freely move across the lattice.

PMID- 21198084
TI  - Resonance tongues in a system of globally coupled FitzHugh-Nagumo oscillators
      with time-periodic coupling strength.
AB  - We investigate the dynamics of a population of globally coupled FitzHugh-Nagumo
      oscillators with a time-periodic coupling strength. While for synchronizing
      global coupling, the in-phase state is always stable, the oscillators split into
      several cluster states for desynchronizing global coupling, most commonly in two,
      irrespective of the coupling strength. This confines the ability of the system to
      form n:m locked states considerably. The prevalence of two and four cluster
      states leads to large 2:1 and 4:1 subharmonic resonance regions, while at low
      coupling strength for a harmonic 1:1 or a superharmonic 1:m time-periodic
      coupling coefficient, any resonances are absent and the system exhibits
      nonresonant phase drifting cluster states. Furthermore, in the unforced, globally
      coupled system the frequency of the oscillators in a cluster state is in general
      lower than that of the uncoupled oscillator and strongly depends on the coupling
      strength. Periodic variation of the coupling strength at twice the natural
      frequency causes each oscillator to keep oscillating with its autonomous
      oscillation period.

PMID- 21198085
TI  - Recurrence-based detection of the hyperchaos-chaos transition in an electronic
      circuit.
AB  - Some complex measures based on recurrence plots give evidence about hyperchaos
      chaos transitions in coupled nonlinear systems [E. G. Souza et al., "Using
      recurrences to characterize the hyperchaos-chaos transition," Phys. Rev. E 78,
      066206 (2008)]. In this paper, these measures are combined with a significance
      test based on twin surrogates to identify such a transition in a fourth-order
      Lorenz-like system, which is able to pass from a hyperchaotic to a chaotic
      behavior for increasing values of a single parameter. A circuit analog of the
      mathematical model has been designed and implemented and the robustness of the
      recurrence-based method on experimental data has been tested. In both the
      numerical and experimental cases, the combination of the recurrence measures and
      the significance test allows to clearly identify the hyperchaos-chaos transition.

PMID- 21198086
TI  - Transport in time-dependent dynamical systems: finite-time coherent sets.
AB  - We study the transport properties of nonautonomous chaotic dynamical systems over
      a finite-time duration. We are particularly interested in those regions that
      remain coherent and relatively nondispersive over finite periods of time, despite
      the chaotic nature of the system. We develop a novel probabilistic methodology
      based upon transfer operators that automatically detect maximally coherent sets.
      The approach is very simple to implement, requiring only singular vector
      computations of a matrix of transitions induced by the dynamics. We illustrate
      our new methodology on an idealized stratospheric flow and in two and three
      dimensional analyses of European Centre for Medium Range Weather Forecasting
      (ECMWF) reanalysis data.

PMID- 21198087
TI  - Characterizing mixed mode oscillations shaped by noise and bifurcation structure.
AB  - Many neuronal systems and models display a certain class of mixed mode
      oscillations (MMOs) consisting of periods of small amplitude oscillations
      interspersed with spikes. Various models with different underlying mechanisms
      have been proposed to generate this type of behavior. Stochastic versions of
      these models can produce similarly looking time series, often with noise-driven
      mechanisms different from those of the deterministic models. We present a suite
      of measures which, when applied to the time series, serves to distinguish models
      and classify routes to producing MMOs, such as noise-induced oscillations or
      delay bifurcation. By focusing on the subthreshold oscillations, we analyze the
      interspike interval density, trends in the amplitude, and a coherence measure. We
      develop these measures on a biophysical model for stellate cells and a
      phenomenological FitzHugh-Nagumo-type model and apply them on related models. The
      analysis highlights the influence of model parameters and resets and return
      mechanisms in the context of a novel approach using noise level to distinguish
      model types and MMO mechanisms. Ultimately, we indicate how the suite of measures
      can be applied to experimental time series to reveal the underlying dynamical
      structure, while exploiting either the intrinsic noise of the system or tunable
      extrinsic noise.

PMID- 21198088
TI  - Chaotic dephasing in a double-slit scattering experiment.
AB  - We design a computational experiment in which a quantum particle tunnels into a
      billiard of variable shape and scatters out of it through a double-slit opening
      on the billiard's base. The interference patterns produced by the scattered
      probability currents for a range of energies are investigated in relation to the
      billiard's geometry which is connected to its classical integrability. Four
      billiards with hierarchical integrability levels are considered: integrable,
      pseudointegrable, weak-mixing, and strongly chaotic. In agreement with the
      earlier result by Casati and Prosen [Phys. Rev. A 72, 032111 (2005)], we find the
      billiard's integrability to have a crucial influence on the properties of the
      interference patterns. In the integrable case, most experiment outcomes are found
      to be consistent with the constructive interference occurring in the usual double
      slit experiment. In contrast to this, nonintegrable billiards typically display
      asymmetric interference patterns of smaller visibility characterized by weakly
      correlated wave function values at the two slits. Our findings indicate an
      intrinsic connection between the classical integrability and the quantum
      dephasing, which is responsible for the destruction of interference.

PMID- 21198089
TI  - Rewiring dynamical networks with prescribed degree distribution for enhancing
      synchronizability.
AB  - In this paper, we present an algorithm for enhancing synchronizability of
      dynamical networks with prescribed degree distribution. The algorithm takes an
      unweighted and undirected network as input and outputs a network with the same
      node-degree distribution and enhanced synchronization properties. The rewirings
      are based on the properties of the Laplacian of the connection graph, i.e., the
      eigenvectors corresponding to the second smallest and the largest eigenvalues of
      the Laplacian. A term proportional to the eigenvectors is adopted to choose
      potential edges for rewiring, provided that the node-degree distribution is
      preserved. The algorithm can be implemented on networks of any sizes as long as
      their eigenvalues and eigenvectors can be calculated with standard algorithms.
      The effectiveness of the proposed algorithm in enhancing the network
      synchronizability is revealed by numerical simulation on a number of sample
      networks including scale-free, Watts-Strogatz, and Erdos-Renyi graphs.
      Furthermore, a number of network's structural parameters such as node betweenness
      centrality, edge betweenness centrality, average path length, clustering
      coefficient, and degree assortativity are tracked as a function of optimization
      steps.

PMID- 21198090
TI  - Regularity analysis of an individual-based ecosystem simulation.
AB  - We analyze the results of a large simulation of an evolving ecosystem to evaluate
      its complexity. In particular, we are interested to know how close to a
      stochastic or a deterministic behavior our simulation is. Four methods have been
      used for this analysis: Higuchi fractal dimension, correlation dimension, largest
      Lyapunov exponent, and P&H method. Besides, we use a surrogate data test to reach
      a final decision about analysis. As we expect, our results show that there is a
      deterministic and chaotic behavior in ecosystem simulation.

PMID- 21198091
TI  - Practical time-delay synchronization of a periodically modulated self-excited
      oscillators with uncertainties.
AB  - This paper studies time-delay synchronization of a periodically modulated Duffing
      Van der Pol (DVP) oscillator subjected to uncertainties with emphasis on complete
      synchronization. A robust adaptive response system is designed to synchronize
      with the uncertain drive periodically modulated DVP oscillator. Adaptation laws
      on the upper bounds of uncertainties are proposed to guarantee the boundedness of
      both the synchronization error and the estimated feedback coupling gains.
      Numerical results are presented to check the effectiveness of the proposed
      synchronization scheme. The results suggest that the linear and nonlinear terms
      in the feedback coupling play a complementary role in increasing the
      synchronization regime in the parameter space of the synchronization manifold.
      The proposed method can be successfully applied to a large variety of physical
      systems.

PMID- 21198092
TI  - Chimeras in a network of three oscillator populations with varying network
      topology.
AB  - We study a network of three populations of coupled phase oscillators with
      identical frequencies. The populations interact nonlocally, in the sense that all
      oscillators are coupled to one another, but more weakly to those in neighboring
      populations than to those in their own population. Using this system as a model
      system, we discuss for the first time the influence of network topology on the
      existence of so-called chimera states. In this context, the network with three
      populations represents an interesting case because the populations may either be
      connected as a triangle, or as a chain, thereby representing the simplest
      discrete network of either a ring or a line segment of oscillator populations. We
      introduce a special parameter that allows us to study the effect of breaking the
      triangular network structure, and to vary the network symmetry continuously such
      that it becomes more and more chain-like. By showing that chimera states only
      exist for a bounded set of parameter values, we demonstrate that their existence
      depends strongly on the underlying network structures, and conclude that chimeras
      exist on networks with a chain-like character.

PMID- 21198093
TI  - A coupled map lattice model for rheological chaos in sheared nematic liquid
      crystals.
AB  - A variety of complex fluids under shear exhibit complex spatiotemporal behavior,
      including what is now termed rheological chaos, at moderate values of the shear
      rate. Such chaos associated with rheological response occurs in regimes where the
      Reynolds number is very small. It must thus arise as a consequence of the
      coupling of the flow to internal structural variables describing the local state
      of the fluid. We propose a coupled map lattice model for such complex
      spatiotemporal behavior in a passively sheared nematic liquid crystal using local
      maps constructed so as to accurately describe the spatially homogeneous case.
      Such local maps are coupled diffusively to nearest and next-nearest neighbors to
      mimic the effects of spatial gradients in the underlying equations of motion. We
      investigate the dynamical steady states obtained as parameters in the map and the
      strength of the spatial coupling are varied, studying local temporal properties
      at a single site as well as spatiotemporal features of the extended system. Our
      methods reproduce the full range of spatiotemporal behavior seen in earlier one
      dimensional studies based on partial differential equations. We report results
      for both the one- and two-dimensional cases, showing that spatial coupling favors
      uniform or periodically time-varying states, as intuitively expected. We
      demonstrate and characterize regimes of spatiotemporal intermittency out of which
      chaos develops. Our work indicates that similar simplified lattice models of the
      dynamics of complex fluids under shear should provide useful ways to access and
      quantify spatiotemporal complexity in such problems, in addition to representing
      a fast and numerically tractable alternative to continuum representations.

PMID- 21198094
TI  - Chaos from turbulence: stochastic-chaotic equilibrium in turbulent convection at
      high Rayleigh numbers.
AB  - It is shown that the correlation function of the mean wind velocity generated by
      a turbulent thermal convection (Rayleigh number Ra ~ 10(11)) exhibits exponential
      decay with a very long correlation time, while the corresponding largest Lyapunov
      exponent is certainly positive. These results together with the reconstructed
      phase portrait indicate the possible presence of chaotic component in the
      examined mean wind. Telegraph approximation is also used to study the relative
      contribution of the chaotic and stochastic components to the mean wind
      fluctuations and an equilibrium between these components has been studied in
      detail.

PMID- 21198095
TI  - Integrability study on a generalized (2+1)-dimensional variable-coefficient
      Gardner model with symbolic computation.
AB  - Gardner model describes certain nonlinear elastic structures, ion-acoustic waves
      in plasmas, and shear flows in ocean and atmosphere. In this paper, by virtue of
      the computerized symbolic computation, the integrability of a generalized (2+1)
      dimensional variable-coefficient Gardner model is investigated. Painleve
      integrability conditions are derived among the coefficient functions, which
      reduce all the coefficient functions to be proportional only to gamma(t), the
      coefficient of the cubic nonlinear term u(2)u(x). Then, an independent
      transformation of the variable t transforms the reduced gamma(t)-dependent
      equation into a constant-coefficient integrable one. Painleve test shows that
      this is the only case when our original generalized (2+1)-dimensional variable
      coefficient Gardner model is integrable.

PMID- 21198096
TI  - Long-term variability of global statistical properties of epileptic brain
      networks.
AB  - We investigate the influence of various pathophysiologic and physiologic
      processes on global statistical properties of epileptic brain networks. We
      construct binary functional networks from long-term, multichannel
      electroencephalographic data recorded from 13 epilepsy patients, and the average
      shortest path length and the clustering coefficient serve as global statistical
      network characteristics. For time-resolved estimates of these characteristics we
      observe large fluctuations over time, however, with some periodic temporal
      structure. These fluctuations can--to a large extent--be attributed to daily
      rhythms while relevant aspects of the epileptic process contribute only
      marginally. Particularly, we could not observe clear cut changes in network
      states that can be regarded as predictive of an impending seizure. Our findings
      are of particular relevance for studies aiming at an improved understanding of
      the epileptic process with graph-theoretical approaches.

PMID- 21198097
TI  - Amplitude and phase effects on the synchronization of delay-coupled oscillators.
AB  - We consider the behavior of Stuart-Landau oscillators as generic limit-cycle
      oscillators when they are interacting with delay. We investigate the role of
      amplitude and phase instabilities in producing symmetry-breaking/restoring
      transitions. Using analytical and numerical methods we compare the dynamics of
      one oscillator with delayed feedback, two oscillators mutually coupled with
      delay, and two delay-coupled elements with self-feedback. Taking only the phase
      dynamics into account, no chaotic dynamics is observed, and the stability of the
      identical synchronization solution is the same in each of the three studied
      networks of delay-coupled elements. When allowing for a variable oscillation
      amplitude, the delay can induce amplitude instabilities. We provide analytical
      proof that, in case of two mutually coupled elements, the onset of an amplitude
      instability always results in antiphase oscillations, leading to a leader-laggard
      behavior in the chaotic regime. Adding self-feedback with the same strength and
      delay as the coupling stabilizes the system in the transverse direction and,
      thus, promotes the onset of identically synchronized behavior.

PMID- 21198098
TI  - Adiabatic description of capture into resonance and surfatron acceleration of
      charged particles by electromagnetic waves.
AB  - We present an analytical and numerical study of the surfatron acceleration of
      nonrelativistic charged particles by electromagnetic waves. The acceleration is
      caused by capture of particles into resonance with one of the waves. We
      investigate capture for systems with one or two waves and provide conditions
      under which the obtained results can be applied to systems with more than two
      waves. In the case of a single wave, the once captured particles never leave the
      resonance and their velocity grows linearly with time. However, if there are two
      waves in the system, the upper bound of the energy gain may exist and we find the
      analytical value of that bound. We discuss several generalizations including the
      relativistic limit, different wave amplitudes, and a wide range of the waves'
      wavenumbers. The obtained results are used for qualitative description of some
      phenomena observed in the Earth's magnetosphere.

PMID- 21198099
TI  - Subordinated diffusion and continuous time random walk asymptotics.
AB  - Anomalous transport is usually described either by models of continuous time
      random walks (CTRWs) or, otherwise, by fractional Fokker-Planck equations
      (FFPEs). The asymptotic relation between properly scaled CTRW and fractional
      diffusion process has been worked out via various approaches widely discussed in
      literature. Here, we focus on a correspondence between CTRWs and time and space
      fractional diffusion equation stemming from two different methods aimed to
      accurately approximate anomalous diffusion processes. One of them is the Monte
      Carlo simulation of uncoupled CTRW with a Levy alpha-stable distribution of jumps
      in space and a one-parameter Mittag-Leffler distribution of waiting times. The
      other is based on a discretized form of a subordinated Langevin equation in which
      the physical time defined via the number of subsequent steps of motion is itself
      a random variable. Both approaches are tested for their numerical performance and
      verified with known analytical solutions for the Green function of a space-time
      fractional diffusion equation. The comparison demonstrates a trade off between
      precision of constructed solutions and computational costs. The method based on
      the subordinated Langevin equation leads to a higher accuracy of results, while
      the CTRW framework with a Mittag-Leffler distribution of waiting times provides
      efficiently an approximate fundamental solution to the FFPE and converges to the
      probability density function of the subordinated process in a long-time limit.

PMID- 21198100
TI  - Identifying complex periodic windows in continuous-time dynamical systems using
      recurrence-based methods.
AB  - The identification of complex periodic windows in the two-dimensional parameter
      space of certain dynamical systems has recently attracted considerable interest.
      While for discrete systems, a discrimination between periodic and chaotic windows
      can be easily made based on the maximum Lyapunov exponent of the system, this
      remains a challenging task for continuous systems, especially if only short time
      series are available (e.g., in case of experimental data). In this work, we
      demonstrate that nonlinear measures based on recurrence plots obtained from such
      trajectories provide a practicable alternative for numerically detecting shrimps.
      Traditional diagonal line-based measures of recurrence quantification analysis as
      well as measures from complex network theory are shown to allow an excellent
      classification of periodic and chaotic behavior in parameter space. Using the
      well-studied Rossler system as a benchmark example, we find that the average path
      length and the clustering coefficient of the resulting recurrence networks are
      particularly powerful discriminatory statistics for the identification of complex
      periodic windows.

PMID- 21198101
TI  - Passage of a monomer through a nonrigid periodical substrate formed by
      noninteracting particles.
AB  - The paper examines a classical system in one degree of freedom: a particle
      (monomer) interacting with a periodic lattice of independent, separated
      oscillators. The monomer can interact with oscillators via a short-range
      attractive potential force. The periodic lattice of oscillators may absorb the
      energy of the monomer launched at some initial velocity, but it does so in a very
      peculiar manner. The monomer velocity gradually decreases, approaching near some
      nonzero limit value. The limiting monomer velocities can assume discrete values
      only. This behavior of the monomer is accounted for by the existing resistance
      force that completely vanishes at certain monomer velocities.

PMID- 21198102
TI  - Novel type of amplitude spiral wave in a two-layer system.
AB  - Interaction of spiral waves in a two-layer system described by a model of coupled
      complex Ginzburg-Landau equations with negative-feedback couplings epsilon(1) and
      epsilon(2) is studied. Synchronization of two spiral waves can be broadly found
      if epsilon(1)+epsilon(2) is sufficiently large. Prior to the synchronization,
      under the condition of strongly asymmetric coupling (?epsilon(1)-epsilon(2)??0),
      a novel type of spiral wave, amplitude spiral wave, exists in the driven system.
      The pattern of amplitude spiral wave shows the spiral in the amplitude and
      without a singularity point (tip), compared to usual spiral waves known for phase
      with amplitude uniform far away from tips and rotating around tips.

PMID- 21198103
TI  - The fractal dimension of cell membrane correlates with its capacitance: a new
      fractal single-shell model.
AB  - The scale-invariant property of the cytoplasmic membrane of biological cells is
      examined by applying the Minkowski-Bouligand method to digitized scanning
      electron microscopy images of the cell surface. The membrane is found to exhibit
      fractal behavior, and the derived fractal dimension gives a good description of
      its morphological complexity. Furthermore, we found that this fractal dimension
      correlates well with the specific membrane dielectric capacitance derived from
      the electrorotation measurements. Based on these findings, we propose a new
      fractal single-shell model to describe the dielectrics of mammalian cells, and
      compare it with the conventional single-shell model (SSM). We found that while
      both models fit with experimental data well, the new model is able to eliminate
      the discrepancy between the measured dielectric property of cells and that
      predicted by the SSM.

PMID- 21198104
TI  - Collective phase chaos in the dynamics of interacting oscillator ensembles.
AB  - We study the chaotic behavior of order parameters in two coupled ensembles of
      self-sustained oscillators. Coupling within each of these ensembles is switched
      on and off alternately, while the mutual interaction between these two subsystems
      is arranged through quadratic nonlinear coupling. We show numerically that in the
      course of alternating Kuramoto transitions to synchrony and back to asynchrony,
      the exchange of excitations between two subpopulations proceeds in such a way
      that their collective phases are governed by an expanding circle map similar to
      the Bernoulli map. We perform the Lyapunov analysis of the dynamics and discuss
      finite-size effects.

PMID- 21198105
TI  - Influence of zero range process interaction on diffusion.
AB  - We study the aspects of diffusion for the case of zero range process interaction
      on scale-free networks, through statistical quantities such as the mean first
      passage time, coverage, mean square displacement etc., and pay attention to how
      the interaction, especially the resulted condensation, influences the diffusion.
      By mean-field theory we show that the statistical quantities of diffusion can be
      significantly reduced by the condensation and can be figured out by the waiting
      time of a particle staying at a node. Numerical simulations have confirmed the
      theoretical predictions.

PMID- 21198106
TI  - Alternative stable scroll waves and conversion of autowave turbulence.
AB  - Rotating spiral and scroll waves (vortices) are investigated in the FitzHugh
      Nagumo model of excitable media. The focus is on a parameter region in which
      there exists bistability between alternative stable vortices with distinct
      periods. Response functions are used to predict the filament tension of the
      alternative scrolls and it is shown that the slow-period scroll has negative
      filament tension, while the filament tension of the fast-period scroll changes
      sign within a hysteresis loop. The predictions are confirmed by direct
      simulations. Further investigations show that the slow-period scrolls display
      features similar to delayed after-depolarization and tend to develop into
      turbulence similar to ventricular fibrillation (VF). Scrolls with positive
      filament tension collapse or stabilize, similar to monomorphic ventricular
      tachycardia (VT). Perturbations, such as boundary interaction or shock stimulus,
      can convert the vortex with negative filament tension into the vortex with
      positive filament tension. This may correspond to transition from VF to VT
      unrelated to pinning.

PMID- 21198107
TI  - Robust synchronization of a class of uncertain chaotic systems based on quadratic
      optimal theory and adaptive strategy.
AB  - This paper presents a chaos synchronization method for a class of uncertain
      chaotic systems using the combination of an optimal control theory and an
      adaptive strategy. A quadratic optimal regulator and an adaptive control are used
      to represent the controller's structure. The asymptotic stability of the
      corresponding error dynamical system is guaranteed through Lyapunov stability
      analysis. The proposed controller is employed in two uncertain chaotic Lu
      systems, and their promising performances are illustrated.

PMID- 21198108
TI  - Planar radial weakly dissipative diffeomorphisms.
AB  - We study the effect of a small dissipative radial perturbation acting on a one
      parameter family of area preserving diffeomorphisms. This is a specific type of
      dissipative perturbation. The interest is on the global effect of the dissipation
      on a fixed domain around an elliptic fixed/periodic point of the family, rather
      than on the effects around a single resonance. We describe the local/global
      bifurcations observed in the transition from the conservative to a weakly
      dissipative case: the location of the resonant islands, the changes in the
      domains of attraction of the foci inside these islands, how the resonances
      disappear, etc. The possible omega-limits are determined in each case. This
      topological description gives rise to three different dynamical regimes according
      to the size of dissipative perturbation. Moreover, we determine the conservative
      limit of the probability of capture in a generic resonance from the interpolating
      flow approximation, hence assuming no homoclinics in the resonance. As a paradigm
      of weakly dissipative radial maps, we use a dissipative version of the Henon map.

PMID- 21198109
TI  - Controlled generation of intrinsic localized modes in microelectromechanical
      cantilever arrays.
AB  - We propose a scheme to induce intrinsic localized modes (ILMs) at an arbitrary
      site in microelectromechanical cantilever arrays. The idea is to locate the
      particular cantilever beam in the array that one wishes to drive to an
      oscillating state with significantly higher amplitude than the average and then
      apply small adjustments to the electrical signal that drives the whole array
      system. Our scheme is thus a global closed-loop control strategy. We argue that
      the dynamical mechanism on which our global driving scheme relies is
      spatiotemporal chaos and we develop a detailed analysis based on the standard
      averaging method in nonlinear dynamics to understand the working of our control
      scheme. We also develop a Markov model to characterize the transient time
      required for inducing ILMs.

PMID- 21198110
TI  - Delay-enhanced spatiotemporal order in coupled neuronal systems.
AB  - In a network of noisy neuron oscillators with time-delayed coupling, we uncover a
      phenomenon of delay-enhanced spatiotemporal order. We find that time delay in the
      coupling can dramatically enhance the temporal coherence and spatial synchrony of
      the noise-induced spike trains. In addition, if the delay time is tuned to nearly
      match the intrinsic spiking period of the neuronal network, both the coherence
      and the synchrony reach maximum levels, demonstrating an interesting type of
      resonance phenomenon with delay. Such findings are shown to be robust to the
      change of the noise intensity and the rewiring probability of small-world
      network.

PMID- 21198111
TI  - DNA-RNA transcription as an impact of viscosity.
AB  - The impact of viscosity on DNA dynamics is studied both analytically and
      numerically. It is assumed that the viscosity exists at the segments where DNA
      molecule is surrounded by RNA polymerase. We demonstrate that the frictional
      forces destroy the modulation of the incoming solitonic wave. We show that
      viscosity, crucial for demodulation, is essential for DNA-RNA transcription.

PMID- 21198112
TI  - Dynamic synchronization of a time-evolving optical network of chaotic
      oscillators.
AB  - We present and experimentally demonstrate a technique for achieving and
      maintaining a global state of identical synchrony of an arbitrary network of
      chaotic oscillators even when the coupling strengths are unknown and time
      varying. At each node an adaptive synchronization algorithm dynamically estimates
      the current strength of the net coupling signal to that node. We experimentally
      demonstrate this scheme in a network of three bidirectionally coupled chaotic
      optoelectronic feedback loops and we present numerical simulations showing its
      application in larger networks. The stability of the synchronous state for
      arbitrary coupling topologies is analyzed via a master stability function
      approach.

PMID- 21198113
TI  - Introduction to focus issue: dynamics in systems biology.
AB  - The methods of nonlinear systems form an extensive toolbox for the study of
      biology, and systems biology provides a rich source of motivation for the
      development of new mathematical techniques and the furthering of understanding of
      dynamical systems. This Focus Issue collects together a large variety of work
      which highlights the complementary nature of these two fields, showing what each
      has to offer the other. While a wide range of subjects is covered, the papers
      often have common themes such as "rhythms and oscillations," "networks and graph
      theory," and "switches and decision making." There is a particular emphasis on
      the links between experimental data and modeling and mathematical analysis.

PMID- 21198114
TI  - Understanding cardiac alternans: a piecewise linear modeling framework.
AB  - Cardiac alternans is a beat-to-beat alternation in action potential duration
      (APD) and intracellular calcium (Ca(2+)) cycling seen in cardiac myocytes under
      rapid pacing that is believed to be a precursor to fibrillation. The cellular
      mechanisms of these rhythms and the coupling between cellular Ca(2+) and voltage
      dynamics have been extensively studied leading to the development of a class of
      physiologically detailed models. These have been shown numerically to reproduce
      many of the features of myocyte response to pacing, including alternans, and have
      been analyzed mathematically using various approximation techniques that allow
      for the formulation of a low dimensional map to describe the evolution of APDs.
      The seminal work by Shiferaw and Karma is of particular interest in this regard
      [Shiferaw, Y. and Karma, A., "Turing instability mediated by voltage and calcium
      diffusion in paced cardiac cells," Proc. Natl. Acad. Sci. U.S.A. 103, 5670-5675
      (2006)]. Here, we establish that the key dynamical behaviors of the Shiferaw
      Karma model are arranged around a set of switches. These are shown to be the main
      elements for organizing the nonlinear behavior of the model. Exploiting this
      observation, we show that a piecewise linear caricature of the Shiferaw-Karma
      model, with a set of appropriate switching manifolds, can be constructed that
      preserves the physiological interpretation of the original model while being
      amenable to a systematic mathematical analysis. In illustration of this point, we
      formulate the dynamics of Ca(2+) cycling (in response to pacing) and compute the
      properties of periodic orbits in terms of a stroboscopic map that can be
      constructed without approximation. Using this, we show that alternans emerge via
      a period-doubling instability and track this bifurcation in terms of
      physiologically important parameters. We also show that when coupled to a
      spatially extended model for Ca(2+) transport, the model supports spatially
      varying patterns of alternans. We analyze the onset of this instability with a
      generalization of the master stability approach to accommodate the nonsmooth
      nature of our system.

PMID- 21198115
TI  - Fibroblasts alter spiral wave stability.
AB  - We consider a three-domain model of cardiac tissue consisting of fibroblasts,
      myocytes, and extracellular space. We show in the one dimensional case that the
      fibroblasts with different resting potentials may alter restitution properties of
      tissue. On this basis we demonstrated that in two dimensional slice of cardiac
      tissue, a spiral wave break up can be caused purely by the influence of
      fibroblasts and, vice-versa, initially unstable spiral can be stabilized by
      fibroblasts depending on the value of their resting potential.

PMID- 21198116
TI  - Understanding anomalous delays in a model of intracellular calcium dynamics.
AB  - In many cell types, oscillations in the concentration of free intracellular
      calcium ions are used to control a variety of cellular functions. It has been
      suggested [J. Sneyd et al., "A method for determining the dependence of calcium
      oscillations on inositol trisphosphate oscillations," Proc. Natl. Acad. Sci.
      U.S.A. 103, 1675-1680 (2006)] that the mechanisms underlying the generation and
      control of such oscillations can be determined by means of a simple experiment,
      whereby a single exogenous pulse of inositol trisphosphate (IP(3)) is applied to
      the cell. However, more detailed mathematical investigations [M. Domijan et al.,
      "Dynamical probing of the mechanisms underlying calcium oscillations," J.
      Nonlinear Sci. 16, 483-506 (2006)] have shown that this is not necessarily always
      true, and that the experimental data are more difficult to interpret than first
      thought. Here, we use geometric singular perturbation techniques to study the
      dynamics of models that make different assumptions about the mechanisms
      underlying the calcium oscillations. In particular, we show how recently
      developed canard theory for singularly perturbed systems with three or more slow
      variables [M. Wechselberger, "A propos de canards (Apropos canards)," Preprint,
      2010] applies to these calcium models and how the presence of a curve of folded
      singularities and corresponding canards can result in anomalous delays in the
      response of these models to a pulse of IP(3).

PMID- 21198117
TI  - Identifiability and observability analysis for experimental design in nonlinear
      dynamical models.
AB  - Dynamical models of cellular processes promise to yield new insights into the
      underlying systems and their biological interpretation. The processes are usually
      nonlinear, high dimensional, and time-resolved experimental data of the processes
      are sparse. Therefore, parameter estimation faces the challenges of structural
      and practical nonidentifiability. Nonidentifiability of parameters induces
      nonobservability of trajectories, reducing the predictive power of the model. We
      will discuss a generic approach for nonlinear models that allows for
      identifiability and observability analysis by means of a realistic example from
      systems biology. The results will be utilized to design new experiments that
      enhance model predictiveness, illustrating the iterative cycle between modeling
      and experimentation in systems biology.

PMID- 21198118
TI  - Mass synchronization: occurrence and its control with possible applications to
      brain dynamics.
AB  - Occurrence of strong or mass synchronization of a large number of neuronal
      populations in the brain characterizes its pathological states. In order to
      establish an understanding of the mechanism underlying such pathological
      synchronization, we present a model of coupled populations of phase oscillators
      representing the interacting neuronal populations. Through numerical analysis, we
      discuss the occurrence of mass synchronization in the model, where a source
      population which gets strongly synchronized drives the target populations onto
      mass synchronization. We hypothesize and identify a possible cause for the
      occurrence of such a synchronization, which is so far unknown: Pathological
      synchronization is caused not just because of the increase in the strength of
      coupling between the populations but also because of the strength of the strong
      synchronization of the drive population. We propose a demand controlled method to
      control this pathological synchronization by providing a delayed feedback where
      the strength and frequency of the synchronization determine the strength and the
      time delay of the feedback. We provide an analytical explanation for the
      occurrence of pathological synchronization and its control in the thermodynamic
      limit.

PMID- 21198119
TI  - On the role of subthreshold currents in the Huber-Braun cold receptor model.
AB  - We study the role of the strength of subthreshold currents in a four-dimensional
      Hodgkin-Huxley-type model of mammalian cold receptors. Since a total diminution
      of subthreshold activity corresponds to a decomposition of the model into a slow,
      subthreshold, and a fast, spiking subsystem, we first elucidate their respective
      dynamics separately and draw conclusions about their role for the generation of
      different spiking patterns. These results motivate a numerical bifurcation
      analysis of the effect of varying the strength of subthreshold currents, which is
      done by varying a suitable control parameter. We work out the key mechanisms
      which can be attributed to subthreshold activity and furthermore elucidate the
      dynamical backbone of different activity patterns generated by this model.

PMID- 21198121
TI  - From simple to complex patterns of oscillatory behavior in a model for the
      mammalian cell cycle containing multiple oscillatory circuits.
AB  - We previously proposed an integrated computational model for the network of
      cyclin-dependent kinases (Cdks) that controls the dynamics of the mammalian cell
      cycle [C. Gerard and A. Goldbeter, "Temporal self-organization of the cyclin/Cdk
      network driving the mammalian cell cycle," Proc. Natl. Acad. Sci. U.S.A. 106,
      21643 (2009)]. The model contains four Cdk modules regulated by reversible
      phosphorylation, Cdk inhibitors, protein synthesis or degradation, and the
      balance between antagonistic effects of the tumor suppressor pRB and the
      transcription factor E2F. Increasing the level of a growth factor above a
      critical threshold triggers the transition from a quiescent, stable steady state
      to self-sustained oscillations in the Cdk network. These oscillations correspond
      to the repetitive, transient activation of cyclin D/Cdk4-6 in G1, cyclin E/Cdk2
      at the G1/S transition, cyclin A/Cdk2 in S and at the S/G2 transition, and cyclin
      B/Cdk1 at the G2/M transition. This periodic, ordered activation of the various
      cyclin/Cdk complexes can be associated with cell proliferation. The multiplicity
      of feedback loops within the Cdk network is such that it contains at least four
      distinct circuits capable of producing oscillations. The tight coupling of these
      oscillatory circuits generally results in simple periodic behavior associated
      with repetitive cycles of mitosis or with endoreplication. The latter corresponds
      to multiple passages through the phase of DNA replication without mitosis. We
      show here that, as a result of the interaction between the multiple oscillatory
      circuits, particularly when attenuating the strength of the oscillatory module
      involving cyclin B/Cdk1, the model for the Cdk network can also produce complex
      periodic oscillations, quasiperiodic oscillations, and chaos. Numerical
      simulations based on limited explorations in parameter space nevertheless suggest
      that these complex modes of oscillatory behavior remain less common than the
      evolution to simple periodic oscillations of the limit cycle type, holding with
      the view that simple periodic oscillations in the Cdk network correspond to its
      physiological mode of dynamic behavior.

PMID- 21198120
TI  - A robust two-gene oscillator at the core of Ostreococcus tauri circadian clock.
AB  - The microscopic green alga Ostreococcus tauri is rapidly emerging as a promising
      model organism in the green lineage. In particular, recent results by Corellou et
      al. [Plant Cell 21, 3436 (2009)] and Thommen et al. [PLOS Comput. Biol. 6,
      e1000990 (2010)] strongly suggest that its circadian clock is a simplified
      version of Arabidopsis thaliana clock, and that it is architectured so as to be
      robust to natural daylight fluctuations. In this work, we analyze the time series
      data from luminescent reporters for the two central clock genes TOC1 and CCA1 and
      correlate them with microarray data previously analyzed. Our mathematical
      analysis strongly supports both the existence of a simple two-gene oscillator at
      the core of Ostreococcus tauri clock and the fact that its dynamics is not
      affected by light in normal entrainment conditions, a signature of its
      robustness.

PMID- 21198122
TI  - Relaxation dynamics and frequency response of a noisy cell signaling network.
AB  - We investigate the dynamics of cell signaling using an experimentally based
      Boolean model of the human fibroblast signal transduction network. We determine
      via systematic numerical simulations the relaxation dynamics of the network in
      response to a constant set of inputs, both in the absence and in the presence of
      environmental fluctuations. We then study the network's response to periodically
      modulated signals, uncovering different types of behaviors for different pairs of
      driven input and output nodes. The phenomena observed include low-pass, high
      pass, and band-pass filtering of the input modulations, among other nontrivial
      responses, at frequencies around the relaxation frequency of the network. The
      results reveal that the dynamic response to the external modulation of
      biologically realistic signaling networks is versatile and robust to noise.

PMID- 21198123
TI  - Topological structures enhance the presence of dynamical regimes in synthetic
      networks.
AB  - Genetic and protein networks, through their underlying dynamical behavior,
      characterize structural and functional cellular processes, and are thus regarded
      as "driving forces" of all living systems. Understanding the rhythm generation
      mechanisms that emerge from such complex networks has benefited in recent years
      by synthetic approaches, through which simpler network modules (e.g., switches
      and oscillators) have been built. In this manner, a significant attention to date
      has been focused on the dynamical behavior of these isolated synthetic circuits,
      and the occurrence of unifying rhythms in systems of globally coupled genetic
      units. In contrast to this, we address here the question: Could topologically
      distinct structures enhance the presence of various dynamical regimes in
      synthetic networks? We show that an intercellular mechanism, engineered to
      operate on a local scale, will inevitably lead to multirhythmicity, and to the
      appearance of several coexisting (complex) dynamical regimes, if certain
      preconditions regarding the dynamical structure of the synthetic circuits are
      met. Moreover, we discuss the importance of regime enhancement in synthetic
      structures in terms of memory storage and computation capabilities.

PMID- 21198124
TI  - Hierarchical genetic networks and noncoding RNAs.
AB  - In eukaryotic cells, many genes are transcribed into noncoding RNAs. Such RNAs
      may associate with mRNAs and inhibit their translation and facilitate
      degradation. To clarify what may happen in this case, we propose a kinetic model
      describing the effect of noncoding RNAs on a mRNA-protein network with the
      hierarchical three-layer architecture. For positive regulation of the layers, our
      model predicts either bistability with a fairly narrow hysteresis loop or a
      unique steady state. For negative or mixed regulation, the steady state is found
      to be unique.

PMID- 21198125
TI  - Emergence of modularity and disassortativity in protein-protein interaction
      networks.
AB  - In this paper, we present a simple evolution model of protein-protein interaction
      networks by introducing a rule of small-preference duplication of a node, meaning
      that the probability of a node chosen to duplicate is inversely proportional to
      its degree, and subsequent divergence plus nonuniform heterodimerization based on
      some plausible mechanisms in biology. We show that our model cannot only
      reproduce scale-free connectivity and small-world pattern, but also exhibit
      hierarchical modularity and disassortativity. After comparing the features of our
      model with those of real protein-protein interaction networks, we believe that
      our model can provide relevant insights into the mechanism underlying the
      evolution of protein-protein interaction networks.

PMID- 21198126
TI  - Evolution of functional subnetworks in complex systems.
AB  - Links in a realistic network may have different functions, which makes the
      network virtually a combination of some small-size functional subnetworks. Here,
      by a model of coupled phase oscillators, we investigate how such functional
      subnetworks are evolved and developed according to the network structure and
      dynamics. In particular, we study the case of evolutionary clustered networks in
      which the function type of each link (attractive or repulsive coupling) is
      adaptively updated according to the local network dynamics. It is found that
      during the process of system evolution, the network is gradually stabilized into
      a particular form in which the attractive (repulsive) subnetwork consists only of
      the intralinks (interlinks). Based on the observed properties of subnetwork
      evolution, we also propose a new algorithm for network partition which, compared
      with the conventional algorithms, is distinguished by its convenient operation
      and fast computing speed.

PMID- 21198127
TI  - Modeling the complex dynamics of enzyme-pathway coevolution.
AB  - Metabolic pathways must have coevolved with the corresponding enzyme gene
      sequences. However, the evolutionary dynamics ensuing from the interplay between
      metabolic networks and genomes is still poorly understood. Here, we present a
      computational model that generates putative evolutionary walks on the metabolic
      network using a parallel evolution of metabolic reactions and their catalyzing
      enzymes. Starting from an initial set of compounds and enzymes, we expand the
      metabolic network iteratively by adding new enzymes with a probability that
      depends on their sequence-based similarity to already present enzymes. Thus, we
      obtain simulated time courses of chemical evolution in which we can monitor the
      appearance of new metabolites, enzyme sequences, or even entire organisms. We
      observe that new enzymes do not appear gradually but rather in clusters which
      correspond to enzyme classes. A comparison with Brownian motion dynamics
      indicates that our system displays biased random walks similar to diffusion on
      the metabolic network with long-range correlations. This suggests that a
      quantitative molecular principle may underlie the appearance of punctuated
      equilibrium dynamics, whereby enzymes occur in bursts rather than by phyletic
      gradualism. Moreover, the simulated time courses lead to a putative time-order of
      enzyme and organism appearance. Among the patterns we detect in these
      evolutionary trends is a significant correlation between the time of appearance
      and their enzyme repertoire size. Hence, our approach to metabolic evolution may
      help understand the rise in complexity at the biochemical and genomic levels.

PMID- 21198128
TI  - Basins of coexistence and extinction in spatially extended ecosystems of
      cyclically competing species.
AB  - Microscopic models based on evolutionary games on spatially extended scales have
      recently been developed to address the fundamental issue of species coexistence.
      In this pursuit almost all existing works focus on the relevant dynamical
      behaviors originated from a single but physically reasonable initial condition.
      To gain comprehensive and global insights into the dynamics of coexistence, here
      we explore the basins of coexistence and extinction and investigate how they
      evolve as a basic parameter of the system is varied. Our model is cyclic
      competitions among three species as described by the classical rock-paper
      scissors game, and we consider both discrete lattice and continuous space,
      incorporating species mobility and intraspecific competitions. Our results reveal
      that, for all cases considered, a basin of coexistence always emerges and
      persists in a substantial part of the parameter space, indicating that
      coexistence is a robust phenomenon. Factors such as intraspecific competition
      can, in fact, promote coexistence by facilitating the emergence of the
      coexistence basin. In addition, we find that the extinction basins can exhibit
      quite complex structures in terms of the convergence time toward the final state
      for different initial conditions. We have also developed models based on partial
      differential equations, which yield basin structures that are in good agreement
      with those from microscopic stochastic simulations. To understand the origin and
      emergence of the observed complicated basin structures is challenging at the
      present due to the extremely high dimensional nature of the underlying dynamical
      system.

PMID- 21198129
TI  - Abundance of stable periodic behavior in a Red Grouse population model with
      delay: a consequence of homoclinicity.
AB  - Shrimp-shaped periodic regions embedded in chaotic regions in two-dimensional
      parameter spaces are of specific interest for physical and biological systems. We
      provide the first observation of these shrimp-shaped stability regions in a
      parameter space of a continuous time-delayed population model, obtained by taking
      the delays as bifurcation parameters. The parameter space organization is
      governed by the presence of infinitely many periodicity hubs, which trigger the
      spiraling organization of these shrimp-shaped periodic regions around them. We
      provide evidence that this spiraling organization in the parameter space is a
      consequence of the existence of homoclinic orbits in the phase space.

PMID- 21198130
TI  - Stochastic characterization of small-scale algorithms for human sensory
      processing.
AB  - Human sensory processing can be viewed as a functional H mapping a stimulus
      vector s into a decisional variable r. We currently have no direct access to r;
      rather, the human makes a decision based on r in order to drive subsequent
      behavior. It is this (typically binary) decision that we can measure. For
      example, there may be two external stimuli s([0]) and s([1]), mapped onto r([0])
      and r([1]) by the sensory apparatus H; the human chooses the stimulus associated
      with largest r. This kind of decisional transduction poses a major challenge for
      an accurate characterization of H. In this article, we explore a specific
      approach based on a behavioral variant of reverse correlation techniques, where
      the input s contains a target signal corrupted by a controlled noisy
      perturbation. The presence of the target signal poses an additional challenge
      because it distorts the otherwise unbiased nature of the noise source. We
      consider issues arising from both the decisional transducer and the target
      signal, their impact on system identification, and ways to handle them
      effectively for system characterizations that extend to second-order functional
      approximations with associated small-scale cascade models.

PMID- 21198131
TI  - Adaptive functional systems: learning with chaos.
AB  - We propose a new model of adaptive behavior that combines a winnerless
      competition principle and chaos to learn new functional systems. The model
      consists of a complex network of nonlinear dynamical elements producing sequences
      of goal-directed actions. Each element describes dynamics and activity of the
      functional system which is supposed to be a distributed set of interacting
      physiological elements such as nerve or muscle that cooperates to obtain certain
      goal at the level of the whole organism. During "normal" behavior, the dynamics
      of the system follows heteroclinic channels, but in the novel situation chaotic
      search is activated and a new channel leading to the target state is gradually
      created simulating the process of learning. The model was tested in single and
      multigoal environments and had demonstrated a good potential for generation of
      new adaptations.

PMID- 21198132
TI  - Different effects of redundant feedback loops on a bistable switch.
AB  - Bistable switches have important roles in cellular decision-making processes.
      Bistability can be the consequence of positive or double-negative feedback loops.
      Although necessary, such feedback is not sufficient for bistability, which also
      requires nonlinearity. Nonlinearity can be provided by synergy of multiple
      feedback loops or by an ultrasensitive response within a single feedback loop.
      However, these two possibilities are not mutually exclusive; a combination of
      them is also possible. Here we analyze a biochemical regulatory network that
      controls a crucial cell cycle transition in all eukaryotic cells and contains
      multiple redundant feedback loops and nonlinearity. We show in this realistic
      biological example that two redundant feedback loops have different effects on
      the position of one of the saddle-node bifurcations of the system, which
      determines where the system switches. This illustrates that even though the roles
      of positive and double-negative feedbacks have been regarded as equivalent, the
      difference in their architectures can lead to differences in their effects on the
      system. We speculate that this conclusion could be general for other bistable
      systems with redundant feedback loops.

PMID- 21198133
TI  - Cell differentiation modeled via a coupled two-switch regulatory network.
AB  - Mesenchymal stem cells can give rise to bone and other tissue cells, but their
      differentiation still escapes full control. In this paper we address this issue
      by mathematical modeling. We present a model for a genetic switch determining the
      cell fate of progenitor cells which can differentiate into osteoblasts (bone
      cells) or chondrocytes (cartilage cells). The model consists of two switch
      mechanisms and reproduces the experimentally observed three stable equilibrium
      states: a progenitor, an osteogenic, and a chondrogenic state. Conventionally,
      the loss of an intermediate (progenitor) state and the entailed attraction to one
      of two opposite (differentiated) states is modeled as a result of changing
      parameters. In our model in contrast, we achieve this by distributing the
      differentiation process to two functional switch parts acting in concert: one
      triggering differentiation and the other determining cell fate. Via stability and
      bifurcation analysis, we investigate the effects of biochemical stimuli
      associated with different system inputs. We employ our model to generate
      differentiation scenarios on the single cell as well as on the cell population
      level. The single cell scenarios allow to reconstruct the switching upon
      extrinsic signals, whereas the cell population scenarios provide a framework to
      identify the impact of intrinsic properties and the limiting factors for
      successful differentiation.

PMID- 21198134
TI  - Spontaneous sarcomere dynamics.
AB  - Sarcomeres are the basic force generating units of striated muscles and consist
      of an interdigitating arrangement of actin and myosin filaments. While muscle
      contraction is usually triggered by neural signals, which eventually set myosin
      motors into motion, isolated sarcomeres can oscillate spontaneously between a
      contracted and a relaxed state. We analyze a model for sarcomere dynamics, which
      is based on a force-dependent detachment rate of myosin from actin. Our numerical
      bifurcation analysis of the spontaneous sarcomere dynamics reveals notably Hopf
      bifurcations, canard explosions, and gluing bifurcations. We discuss possible
      implications for experiments.

PMID- 21198135
TI  - Blood flow in microvascular networks: a study in nonlinear biology.
AB  - Plasma skimming and the Fahraeus-Lindqvist effect are well-known phenomena in
      blood rheology. By combining these peculiarities of blood flow in the
      microcirculation with simple topological models of microvascular networks, we
      have uncovered interesting nonlinear behavior regarding blood flow in networks.
      Nonlinearity manifests itself in the existence of multiple steady states. This is
      due to the nonlinear dependence of viscosity on blood cell concentration.
      Nonlinearity also appears in the form of spontaneous oscillations in limit
      cycles. These limit cycles arise from the fact that the physics of blood flow can
      be modeled in terms of state dependent delay equations with multiple interacting
      delay times. In this paper we extend our previous work on blood flow in a simple
      two node network and begin to explore how topological complexity influences the
      dynamics of network blood flow. In addition we present initial evidence that the
      nonlinear phenomena predicted by our model are observed experimentally.

PMID- 21198136
TI  - Cardiovascular regulation during sleep quantified by symbolic coupling traces.
AB  - Sleep is a complex regulated process with short periods of wakefulness and
      different sleep stages. These sleep stages modulate autonomous functions such as
      blood pressure and heart rate. The method of symbolic coupling traces (SCT) is
      used to analyze and quantify time-delayed coupling of these measurements during
      different sleep stages. The symbolic coupling traces, defined as the symmetric
      and diametric traces of the bivariate word distribution matrix, allow the
      quantification of time-delayed coupling. In this paper, the method is applied to
      heart rate and systolic blood pressure time series during different sleep stages
      for healthy controls as well as for normotensive and hypertensive patients with
      sleep apneas. Using the SCT, significant different cardiovascular mechanisms not
      only between the deep sleep and the other sleep stages but also between healthy
      subjects and patients can be revealed. The SCT method is applied to model
      systems, compared with established methods, such as cross correlation, mutual
      information, and cross recurrence analysis and demonstrates its advantages
      especially for nonstationary physiological data. As a result, SCT proves to be
      more specific in detecting delays of directional interactions than standard
      coupling analysis methods and yields additional information which cannot be
      measured by standard parameters of heart rate and blood pressure variability. The
      proposed method may help to indicate the pathological changes in cardiovascular
      regulation and also the effects of continuous positive airway pressure therapy on
      the cardiovascular system.

PMID- 21198137
TI  - Hybrid optimal scheduling for intermittent androgen suppression of prostate
      cancer.
AB  - We propose a method for achieving an optimal protocol of intermittent androgen
      suppression for the treatment of prostate cancer. Since the model that reproduces
      the dynamical behavior of the surrogate tumor marker, prostate specific antigen,
      is piecewise linear, we can obtain an analytical solution for the model. Based on
      this, we derive conditions for either stopping or delaying recurrent disease. The
      solution also provides a design principle for the most favorable schedule of
      treatment that minimizes the rate of expansion of the malignant cell population.

PMID- 21198142
TI  - Noninvasive assessment of breast cancer risk using time-resolved diffuse optical
      spectroscopy.
AB  - Breast density is a recognized strong and independent risk factor for breast
      cancer. We propose the use of time-resolved transmittance spectroscopy to
      estimate breast tissue density and potentially provide even more direct
      information on breast cancer risk. Time-resolved optical mammography at seven
      wavelengths (635 to 1060 nm) is performed on 49 subjects. Average information on
      breast tissue of each subject is obtained on oxy- and deoxyhemoglobin, water,
      lipids, and collagen content, as well as scattering amplitude and power. All
      parameters, except for blood volume and oxygenation, correlate with mammographic
      breast density, even if not to the same extent. A synthetic optical index proves
      to be quite effective in separating different breast density categories. Finally,
      the estimate of collagen content as a more direct means for the assessment of
      breast cancer risk is discussed.

PMID- 21198143
TI  - Selective suppression of two-photon fluorescence in laser scanning microscopy by
      ultrafast pulse-train excitation.
AB  - Selective excitation of a particular fluorophore in the presence of others
      demands clever design of the optical field interacting with the molecules. We
      describe the use of 20- to 50-GHz pulse-train excitation leading to two-photon
      absorption, followed by successive one-photon stimulated emission as a potential
      technique in the context of controlling two-photon molecular fluorescence, with
      applications in microscopy.

PMID- 21198144
TI  - Spectroscopic visualization of nanoscale deformation in bone: interaction of
      light with partially disordered nanostructure.
AB  - Given that bone is an intriguing nanostructured dielectric as a partially
      disordered complex structure, we apply an elastic light scattering-based approach
      to image prefailure deformation and damage of bovine cortical bone under
      mechanical testing. We demonstrate that our imaging method can capture nanoscale
      deformation in a relatively large area. The unique structure, the high
      anisotropic property of bone, and the system configuration further allow us to
      use the transfer matrix method to study possible spectroscopic manifestations of
      prefailure deformation. Our sensitive yet simple imaging method could potentially
      be used to detect nanoscale structural and mechanical alterations of hard tissue
      and biomaterials in a fairly large field of view.

PMID- 21198145
TI  - Single-molecule imaging of hyaluronan in human synovial fluid.
AB  - Human synovial fluid contains a high concentration of hyaluronan, a high
      molecular weight glycosaminoglycan that provides viscoelasticity and contributes
      to joint lubrication. In osteoarthritis synovial fluid, the concentration and
      molecular weight of hyaluronan decrease, thus impairing shock absorption and
      lubrication. Consistently, substitution of hyaluronan (viscosupplementation) is a
      widely used treatment for osteoarthritis. So far, the organization and dynamics
      of hyaluronan in native human synovial fluid and its action mechanism in
      viscosupplementation are poorly characterized at the molecular level. Here, we
      introduce highly sensitive single molecule microscopy to analyze the conformation
      and interactions of fluorescently labeled hyaluronan molecules in native human
      synovial fluid. Our findings are consistent with a random coil conformation of
      hyaluronan in human synovial fluid, and point to specific interactions of
      hyaluronan molecules with the synovial fluid matrix. Furthermore, single molecule
      microscopy is capable of detecting the breakdown of the synovial fluid matrix in
      osteoarthritis. Thus, single molecule microscopy is a useful new method to probe
      the structure of human synovial fluid and its changes in disease states like
      osteoarthritis.

PMID- 21198146
TI  - Optical imaging of reporter gene expression using a positron-emission-tomography
      probe.
AB  - Reporter gene/reporter probe technology is one of the most important techniques
      in molecular imaging. Lately, many reporter gene/reporter probe systems have been
      coupled to different imaging modalities such as positron emission tomography
      (PET) and optical imaging (OI). It has been recently found that OI techniques
      could be used to monitor radioactive tracers in vitro and in living subjects. In
      this study, we further demonstrate that a reporter gene/nuclear reporter probe
      system [herpes simplex virus type-1 thymidine kinase (HSV1-tk) and 9-(4-(18)F
      fluoro-3-[hydroxymethyl] butyl) guanine ([(18)F]FHBG)] could be successfully
      imaged by OI in vitro and in vivo. OI with radioactive reporter probes will
      facilitate and broaden the applications of reporter gene/reporter probe
      techniques in medical research.

PMID- 21198147
TI  - Fiber-optic nonlinear endomicroscopy with focus scanning by using shape memory
      alloy actuation.
AB  - A miniature fiber optic endomicroscope with built-in dynamic focus scanning
      capability is developed for the first time for 3-D two-photon fluorescence (TPF)
      imaging of biological samples. Fast 2-D lateral beam scanning is realized by
      resonantly vibrating a double-clad fiber cantilever with a tubular piezoactuator.
      Slow axial scanning is achieved by moving the distal end of the imaging probe
      with an extremely compact electrically driven shape memory alloy (SMA). The 10-mm
      long SMA allows 150-MUm contractions with a driving voltage varying only from 50
      to 100 mV. The response of the SMA contraction with the applied voltage is
      nonlinear, but repeatable and can be accurately calibrated. Depth-resolved
      imaging of acriflavine-stained biological tissues and unstained white paper with
      the endomicroscope is performed, and the results demonstrate the feasibility of 3
      D nonlinear optical imaging with the SMA-based scanning fiber-optic
      endomicroscope.

PMID- 21198148
TI  - Simultaneous assessment of pulsating and total blood in inflammatory skin lesions
      using functional diffuse reflectance spectroscopy in the visible range.
AB  - We present a simple and cost-effective optical technique for the simultaneous
      assessment of pulsating and total blood noninvasively in an inflammatory skin
      lesion. Acquisitions of diffuse reflectance spectra in the visible range at 6 Hz
      are used to trace the oscillating components of reflectance. Measurements on
      erythematous lesions from a UV insult show slow changing signal at about 0.1 Hz
      and heart-driven regular oscillations at about 1 Hz simultaneously. The results
      demonstrate the potential of the technique in monitoring both pulsating and
      steady components of the blood in inflammatory lesions of the skin.

PMID- 21198149
TI  - Optical diagnostic and biophotonic methods from bench to bedside.

PMID- 21198150
TI  - "Seeing" electroencephalogram through the skull: imaging prefrontal cortex with
      fast optical signal.
AB  - Near-infrared spectroscopy is a novel imaging technique potentially sensitive to
      both brain hemodynamics (slow signal) and neuronal activity (fast optical signal,
      FOS). The big challenge of measuring FOS noninvasively lies in the presumably low
      signal-to-noise ratio. Thus, detectability of the FOS has been controversially
      discussed. We present reliable detection of FOS from 11 individuals concurrently
      with electroencephalogram (EEG) during a Go-NoGo task. Probes were placed
      bilaterally over prefrontal cortex. Independent component analysis (ICA) was used
      for artifact removal. Correlation coefficient in the best correlated FOS-EEG ICA
      pairs was highly significant (p < 10(-8)), and event-related optical signal
      (EROS) was found in all subjects. Several EROS components were similar to the
      event-related potential (ERP) components. The most robust "optical N200" at t =
      225 ms coincided with the N200 ERP; both signals showed significant difference
      between targets and nontargets, and their timing correlated with subject's
      reaction time. Correlation between FOS and EEG even in single trials provides
      further evidence that at least some FOS components "reflect" electrical brain
      processes directly. The data provide evidence for the early involvement of
      prefrontal cortex in rapid object recognition. EROS is highly localized and can
      provide cost-effective imaging tools for cortical mapping of cognitive processes.

PMID- 21198152
TI  - Segmentation and quantification of retinal lesions in age-related macular
      degeneration using polarization-sensitive optical coherence tomography.
AB  - We present polarization-sensitive optical coherence tomography (PS-OCT) for
      quantitative assessment of retinal pathologies in age-related macular
      degeneration (AMD). On the basis of the polarization scrambling characteristics
      of the retinal pigment epithelium, novel segmentation algorithms were developed
      that allow one to segment pathologic features such as drusen and atrophic zones
      in dry AMD as well as to determine their dimensions. Results from measurements in
      the eyes of AMD patients prove the ability of PS-OCT for quantitative imaging
      based on the retinal features polarizing properties. Repeatability measurements
      were performed in retinas diagnosed with drusen and geographic atrophy in order
      to evaluate the performance of the described methods. PS-OCT appears as a
      promising imaging modality for three-dimensional retinal imaging and ranging with
      additional contrast based on the structures' tissue-inherent polarization
      properties.

PMID- 21198151
TI  - Image guided near-infrared spectroscopy of breast tissue in vivo using boundary
      element method.
AB  - We demonstrate quantitative functional imaging using image-guided near-infrared
      spectroscopy (IG-NIRS) implemented with the boundary element method (BEM) for
      reconstructing 3-D optical property estimates in breast tissue in vivo. A
      multimodality MRI-NIR system was used to collect measurements of light
      reflectance from breast tissue. The BEM was used to model light propagation in 3
      D based only on surface discretization in order to reconstruct quantitative
      values of total hemoglobin (HbT), oxygen saturation, water, and scatter. The
      technique was validated in experimental measurements from heterogeneous breast
      shaped phantoms with known values and applied to a total of seven subjects
      comprising six healthy individuals and one participant with cancer imaged at two
      time points during neoadjuvant chemotherapy. Using experimental measurements from
      a heterogeneous breast phantom, BEM for IG-NIRS produced accurate values for HbT
      in the inclusion with a <3% error. Healthy breast tissues showed higher HbT and
      water in fibroglandular tissue than in adipose tissue. In a subject with cancer,
      the tumor showed higher HbT compared to the background. HbT in the tumor was
      reduced by 9 MUM during treatment. We conclude that 3-D MRI-NIRS with BEM
      provides quantitative and functional characterization of breast tissue in vivo
      through measurement of hemoglobin content. The method provides potentially
      complementary information to DCE-MRI for tumor characterization.

PMID- 21198153
TI  - Visibility of trabecular meshwork by standard and polarization-sensitive optical
      coherence tomography.
AB  - Polarization-sensitive optical coherence tomography (PS-OCT) is known to be
      advantageous because of its additional tissue-specific contrast of the anterior
      eye. So far, this advantage has been shown only qualitatively. We evaluate the
      improved visibility afforded by 3-D PS corneal and anterior eye segment OCT (PS
      CAS-OCT) in visualizing the trabecular meshwork (TM) based on statistical
      evidences. A total of 31 normal subjects participated in this study. The anterior
      eye segments of both the eyes of the subjects are scanned using a custom-made PS
      CAS-OCT and the standard-scattering OCT (S-OCT) and polarization-sensitive phase
      retardation OCT (P-OCT) images are obtained. Three graders grade the visibility
      of the TM using a four-leveled grading system. The intergrader agreement,
      intermodality differences, and interquadrant dependence of visibility are
      statistically examined. All three of three combinations of graders show
      substantial agreement in visibility with P-OCT (rho = 0.74, 0.70, and 0.68,
      Spearman's correlation), while only one of three shows substantial agreement with
      S-OCT (rho = 0.72). Significant dependence of the visibility on the modality (S
      OCT versus P-OCT) and quadrants are found by the analysis of variance. A
      subsequent Wilcoxon signed-rank test reveals significantly improved visibility.
      PS-CAS-OCT may become a useful tool for screening angle-closure glaucoma.

PMID- 21198154
TI  - Light-guided lumpectomy: device and case report.
AB  - We describe the development, design, fabrication, and testing of an optical wire
      to assist in the surgical removal of small lesions during breast-conserving
      surgery. We modify a standard localization wire by adding a 200-MUm optical fiber
      alongside it; the resulting optical wire fit through an 18 gauge needle for
      insertion in the breast. The optical wire is anchored in the lesion by a
      radiologist under ultrasonic and mammographic guidance. At surgery, the tip is
      illuminated with an eye-safe, red, HeNe laser, and the resulting glowball of
      light in the breast tissue surrounds the lesion. The surgeon readily visualizes
      the glowball in the operating room. This glowball provides sufficient feedback to
      the surgeon that it is used (1) to find the lesion and (2) as a guide during
      resection. Light-guided lumpectomy is a simple enhancement to traditional wire
      localization that could improve the current standard of care for surgical
      treatment of small, nonpalpable breast lesions.

PMID- 21198155
TI  - Remote estimation of blood pulse pressure via temporal tracking of reflected
      secondary speckles pattern.
AB  - We present a novel technique for remote noncontact blood pulse pressure
      measurement. It is based on tracking both temporal and amplitude changes of
      reflected secondary speckle produced in human skin when illuminated by a laser
      beam. The implemented technique extracts the difference between the systolic and
      the diastolic blood pressure. Experimental results are presented showing good
      agreement when compared with conventional measurement methods.

PMID- 21198156
TI  - Optical bedside monitoring of cerebral perfusion: technological and
      methodological advances applied in a study on acute ischemic stroke.
AB  - We present results of a clinical study on bedside perfusion monitoring of the
      human brain by optical bolus tracking. We measure the kinetics of the contrast
      agent indocyanine green using time-domain near-IR spectroscopy (tdNIRS) in 10
      patients suffering from acute unilateral ischemic stroke. In all patients, a
      delay of the bolus over the affected when compared to the unaffected hemisphere
      is found (mean: 1.5 s, range: 0.2 s to 5.2 s). A portable time-domain near-IR
      reflectometer is optimized and approved for clinical studies. Data analysis based
      on statistical moments of time-of-flight distributions of diffusely reflected
      photons enables high sensitivity to intracerebral changes in bolus kinetics.
      Since the second centralized moment, variance, is preferentially sensitive to
      deep absorption changes, it provides a suitable representation of the cerebral
      signals relevant for perfusion monitoring in stroke. We show that variance-based
      bolus tracking is also less susceptible to motion artifacts, which often occur in
      severely affected patients. We present data that clearly manifest the
      applicability of the tdNIRS approach to assess cerebral perfusion in acute stroke
      patients at the bedside. This may be of high relevance to its introduction as a
      monitoring tool on stroke units.

PMID- 21198157
TI  - Diffuse reflectance spectroscopy for in vivo pediatric brain tumor detection.
AB  - The concept of using diffuse reflectance spectroscopy to distinguish
      intraoperatively between pediatric brain tumors and normal brain parenchyma at
      the edge of resection cavities is evaluated using an in vivo human study. Diffuse
      reflectance spectra are acquired from normal and tumorous brain areas of 12
      pediatric patients during their tumor resection procedures, using a spectroscopic
      system with a handheld optical probe. A total of 400 spectra are acquired at the
      rate of 33 Hz from a single investigated site, from which the mean spectrum and
      the standard deviation are calculated. The mean diffuse reflectance spectra
      collected are divided into the normal and the tumorous categories in accordance
      with their corresponding results of histological analysis. Statistical methods
      are used to identify those spectral features that effectively separated the two
      tissue categories, and to quantify the spectral variations induced by the motion
      of the handheld probe during a single spectral acquisition procedure. The results
      show that diffuse reflectance spectral intensities between 600 and 800 nm are
      effective in terms of differentiating normal cortex from brain tumors.
      Furthermore, probe movements induce large variations in spectral intensities
      (i.e., larger standard deviation) between 400 and 600 nm.

PMID- 21198158
TI  - Angular domain transillumination imaging optimization with an ultrafast gated
      camera.
AB  - By employing high-aspect-ratio parallel microchannels as an angular filter,
      quasiballistic photons sensitive to internal structures in a turbid medium can be
      captured. Scattered photons exiting the turbid medium typically exhibit
      trajectories with random angles compared to the initial trajectory and are mostly
      rejected by the filter. However, angular filter arrays cannot differentiate
      between quasiballistic photons (early arriving) and photons that happen to attain
      a scattered trajectory that is within the acceptance angle (late arriving).
      Therefore, we have two objectives: (1) to experimentally characterize the angular
      distribution and proportion of minimally deviated quasiballistic photons and
      multiply scattered photons in a turbid medium and (2) to combine time and angular
      gating principles so that early and late arriving photons can be distinguished.
      From the angular distribution data, the angular filter with angular acceptance
      about 0.4 deg yields the highest image contrast for transillumination images. The
      use of angular domain imaging(ADI) with time-gating enables visualization of
      submillimeter absorbing objects with approximately seven times higher image
      contrast compared to ADI in a turbid medium with a scattering level of six times
      the reduced mean free path.

PMID- 21198159
TI  - Semiautomatic segmentation and quantification of calcified plaques in
      intracoronary optical coherence tomography images.
AB  - Coronary calcified plaque (CP) is both an important marker of atherosclerosis and
      major determinant of the success of coronary stenting. Intracoronary optical
      coherence tomography (OCT) with high spatial resolution can provide detailed
      volumetric characterization of CP. We present a semiautomatic method for
      segmentation and quantification of CP in OCT images. Following segmentation of
      the lumen, guide wire, and arterial wall, the CP was localized by edge detection
      and traced using a combined intensity and gradient-based level-set model. From
      the segmentation regions, quantification of the depth, area, angle fill fraction,
      and thickness of the CP was demonstrated. Validation by comparing the automatic
      results to expert manual segmentation of 106 in vivo images from eight patients
      showed an accuracy of 78+/-9%. For a variety of CP measurements, the bias was
      insignificant (except for depth measurement) and the agreement was adequate when
      the CP has a clear outer border and no guide-wire overlap. These results suggest
      that the proposed method can be used for automated CP analysis in OCT, thereby
      facilitating our understanding of coronary artery calcification in the process of
      atherosclerosis and helping guide complex interventional strategies in coronary
      arteries with superficial calcification.

PMID- 21198160
TI  - Optical fiber probe spectroscopy for laparoscopic monitoring of tissue
      oxygenation during esophagectomies.
AB  - Anastomotic complication is a major morbidity associated with esophagectomy.
      Gastric ischemia after conduit creation contributes to anastomotic complications,
      but a reliable method to assess oxygenation in the gastric conduit is lacking. We
      hypothesize that fiber optic spectroscopy can reliably assess conduit
      oxygenation, and that intraoperative gastric ischemia will correlate with the
      development of anastomotic complications. A simple optical fiber probe
      spectrometer is designed for nondestructive laparoscopic measurement of blood
      content and hemoglobin oxygen saturation in the stomach tissue microvasculature
      during human esophagectomies. In 22 patients, the probe measured the light
      transport in stomach tissue between two fibers spaced 3-mm apart (500- to 650-nm
      wavelength range). The stomach tissue site of measurement becomes the site of a
      gastroesophageal anastamosis following excision of the cancerous esophagus and
      surgical ligation of two of the three gastric arteries that provide blood
      perfusion to the anastamosis. Measurements are made at each of five steps
      throughout the surgery. The resting baseline saturation is 0.51+/-0.15 and
      decreases to 0.35+/-0.20 with ligation. Seven patients develop anastomotic
      complications, and a decreased saturation at either of the last two steps
      (completion of conduit and completion of anastamosis) is predictive of
      complication with a sensitivity of 0.71 when the specificity equaled 0.71.

PMID- 21198161
TI  - Automated detection of malignant features in confocal microscopy on superficial
      spreading melanoma versus nevi.
AB  - In-vivo reflectance confocal microscopy (RCM) shows promise for the early
      detection of superficial spreading melanoma (SSM). RCM of SSM shows pagetoid
      melanocytes (PMs) in the epidermis and disarray at the dermal-epidermal junction
      (DEJ), which are automatically quantified with a computer algorithm that locates
      depth of the most superficial pigmented surface [D(SPS)(x,y)] containing PMs in
      the epidermis and pigmented basal cells near the DEJ. The algorithm uses 200
      noninvasive confocal optical sections that image the superficial 200 MUm of ten
      skin sites: five unequivocal SSMs and five nevi. The pattern recognition
      algorithm automatically identifies PMs in all five SSMs and finds none in the
      nevi. A large mean gradient psi (roughness) between laterally adjacent points on
      D(SPS)(x,y) identifies DEJ disruption in SSM psi = 11.7 +/- 3.7 [-] for n = 5
      SSMs versus a small psi = 5.5 +/- 1.0 [-] for n = 5 nevi (significance, p =
      0.0035). Quantitative endpoint metrics for malignant characteristics make digital
      RCM data an attractive diagnostic asset for pathologists, augmenting studies thus
      far, which have relied largely on visual assessment.

PMID- 21198162
TI  - Simple and objective method for routine detection of the macular pigment
      xanthophyll.
AB  - A new simple method for two-dimensional determination of optical density of
      macular pigment xanthophyll (ODx) in clinical routine is based on a single blue
      reflection fundus image. Individual different vignetting is corrected by a
      shading function. For its construction, nodes are automatically found in
      structureless image regions. The influence of stray light in elderly crystalline
      lenses is compensated by a correction function that depends on age. The
      reproducibility of parameters in a one-wavelength reflection method determined
      for three subjects (47, 61, and 78 years old) was: maxODx = 6.3%, meanODx = 4.6%,
      volume = 6%, and area = 6% already before stray-light correction. ODx was
      comparable in pseudophakic and in an eye with a crystalline lens of the same 11
      subjects after stray-light correction. Significant correlation in ODx was found
      between the one-wavelength reflection method and the two-wavelength
      autofluorescence method for pseudophakic and cataract eyes of 19 patients
      suffering from dry age-related macular degeneration (AMD) (R(2) = 0.855). In
      pseudophakic eyes, maxODx was significantly lower for dry AMD (n = 45) (ODx =
      0.491+/-0.102 ODU) than in eyes with healthy fundus (n = 22) (ODx = 0.615+/-0.103
      ODU) (p = 0.000033). Also in eyes with crystalline lens, maxODx was lower in AMD
      (n = 125) (ODx = 0.610+/-0.093 ODU) than in healthy subjects (n = 45) (ODx =
      0.674+/-0.098 ODU) (p = 0.00019). No dependence on age was found in the
      pseudophakic eyes both of healthy subjects and AMD patients.

PMID- 21198163
TI  - Predicting neuropathic ulceration: analysis of static temperature distributions
      in thermal images.
AB  - Foot ulcers affect millions of Americans annually. Conventional methods used to
      assess skin integrity, including inspection and palpation, may be valuable
      approaches, but they usually do not detect changes in skin integrity until an
      ulcer has already developed. We analyze the feasibility of thermal imaging as a
      technique to assess the integrity of the skin and its many layers. Thermal images
      are analyzed using an asymmetry analysis, combined with a genetic algorithm, to
      examine the infrared images for early detection of foot ulcers. Preliminary
      results show that the proposed technique can reliably and efficiently detect
      inflammation and hence effectively predict potential ulceration.

PMID- 21198164
TI  - Wavelength optimization for rapid chromophore mapping using spatial frequency
      domain imaging.
AB  - Spatial frequency-domain imaging (SFDI) utilizes multiple-frequency structured
      illumination and model-based computation to generate two-dimensional maps of
      tissue absorption and scattering properties. SFDI absorption data are measured at
      multiple wavelengths and used to fit for the tissue concentration of intrinsic
      chromophores in each pixel. This is done with a priori knowledge of the basis
      spectra of common tissue chromophores, such as oxyhemoglobin (ctO(2)Hb),
      deoxyhemoglobin (ctHHb), water (ctH(2)O), and bulk lipid. The quality of in vivo
      SFDI fits for the hemoglobin parameters ctO(2)Hb and ctHHb is dependent on
      wavelength selection, fitting parameters, and acquisition rate. The latter is
      critical because SFDI acquisition time is up to six times longer than planar two
      wavelength multispectral imaging due to projection of multiple-frequency spatial
      patterns. Thus, motion artifact during in vivo measurements compromises the
      quality of the reconstruction. Optimal wavelength selection is examined through
      matrix decomposition of basis spectra, simulation of data, and dynamic in vivo
      measurements of a human forearm during cuff occlusion. Fitting parameters that
      minimize cross-talk from additional tissue chromophores, such as water and lipid,
      are determined. On the basis of this work, a wavelength pair of 670 nm/850 nm is
      determined to be the optimal two-wavelength combination for in vivo hemodynamic
      tissue measurements provided that assumptions for water and lipid fractions are
      made in the fitting process. In our SFDI case study, wavelength optimization
      reduces acquisition time over 30-fold to 1.5s compared to 50s for a full 34
      wavelength acquisition. The wavelength optimization enables dynamic imaging of
      arterial occlusions with improved spatial resolution due to reduction of motion
      artifacts.

PMID- 21198165
TI  - Photon-cell interactive Monte Carlo model based on the geometric optics theory
      for photon migration in blood by incorporating both extra- and intracellular
      pathways.
AB  - A photon-cell interactive Monte Carlo (pciMC) that tracks photon migration in
      both the extra- and intracellular spaces is developed without using macroscopic
      scattering phase functions and anisotropy factors, as required for the
      conventional Monte Carlos (MCs). The interaction of photons at the plasma-cell
      boundary of randomly oriented 3-D biconcave red blood cells (RBCs) is modeled
      using the geometric optics. The pciMC incorporates different photon velocities
      from the extra- to intracellular space, whereas the conventional MC treats RBCs
      as points in the space with a constant velocity. In comparison to the
      experiments, the pciMC yielded the mean errors in photon migration time of 9.8+/
      6.8 and 11.2+/-8.5% for suspensions of small and large RBCs (RBC(small),
      RBC(large)) averaged over the optically diffusing region from 2000 to 4000 MUm,
      while the conventional random walk Monte Carlo simulation gave statistically
      higher mean errors of 19.0+/-5.8 ( p < 0.047) and 21.7+/-19.1% (p < 0.055),
      respectively. The gradients of optical density in the diffusing region yielded
      statistically insignificant differences between the pciMC and experiments with
      the mean errors between them being 1.4 and 0.9% in RBC(small) and RBC(larger),
      respectively. The pciMC based on the geometric optics can be used to accurately
      predict photon migration in the optically diffusing, turbid medium.

PMID- 21198166
TI  - Study of laser-induced thermoelastic deformation of native and coagulated ex-vivo
      bovine liver tissues for estimating their optical and thermomechanical
      properties.
AB  - Several studies have explored the potential of optoacoustic imaging for
      monitoring thermal therapies, yet the origin of the contrast in the images is not
      well understood. A technique is required to measure the changes in the optical
      and thermomechanical properties of tissues upon coagulation to better understand
      this contrast. An interferometric method is presented for measuring
      simultaneously the optical and thermomechanical properties of native and
      coagulated ex-vivo bovine tissue samples based on analysis of the surface
      displacement of irradiated samples. Surface displacements are measured after
      irradiation by short laser pulses at 750 nm. A 51% decrease in the optical
      attenuation depth is observed for coagulated liver samples compared to native
      samples. No significant differences in the Gruneisen coefficient are measured in
      the native and coagulated tissue samples. A mean value of 0.12 for the Gruneisen
      coefficient is measured for both native and coagulated liver tissues. The
      displacement profiles exhibit consistent differences between the two tissue
      types. To assess the changes in the sample mechanical properties, the
      experimental data also are compared to numerical solutions of the equation for
      thermoelastic deformation. The results demonstrate that differences in the tissue
      expansion dynamics arise from higher values of elastic modulus for coagulated
      liver samples compared to native ones.

PMID- 21198167
TI  - Specific collection of adherent cells using laser release in a droplet-driven
      capillary cell.
AB  - Laser pressure catapulting of adherent cells directly or cells grown on
      micropallets are two common methods of dislodgement. We describe a method where
      laser catapulting is performed as a flow is introduced orthogonally in a simple
      capillary chamber that is inexpensive and obviates flow-generating devices. The
      moving cells terminate near the contact line within the liquid medium, ensuring
      that they remain continuously hydrated and where the surface-tension forces hold
      them in place to permit a later collection process with a receptacle. By
      dislodging the cells close to the free edge of the liquid chamber, the amount of
      cell travel and, thus, contamination is minimized. The metrics of cell death and
      movement show that firing of the laser beam center a distance away from the cell
      to create a bubble that cavitates over time is more viable with the technique
      than directly on the cell.

PMID- 21198168
TI  - Optimal algorithm for automatic detection of microaneurysms based on receiver
      operating characteristic curve.
AB  - Microaneurysms (MAs) are the first manifestations of the diabetic retinopathy
      (DR) as well as an indicator for its progression. Their automatic detection plays
      a key role for both mass screening and monitoring and is therefore in the core of
      any system for computer-assisted diagnosis of DR. The algorithm basically
      comprises the following stages: candidate detection aiming at extracting the
      patterns possibly corresponding to MAs based on mathematical morphological black
      top hat, feature extraction to characterize these candidates, and classification
      based on support vector machine (SVM), to validate MAs. Feature vector and kernel
      function of SVM selection is very important to the algorithm. We use the receiver
      operating characteristic (ROC) curve to evaluate the distinguishing performance
      of different feature vectors and different kernel functions of SVM. The ROC
      analysis indicates the quadratic polynomial SVM with a combination of features as
      the input shows the best discriminating performance.

PMID- 21198169
TI  - Directional model analysis of the spectral reflection from the fovea and para
      fovea.
AB  - Directional and nondirectional spectral reflection data from 0, 1, 2, 4, and 8
      deg eccentricity, and the optic disk, were analyzed from 400 to 950 nm with an
      existing optical reflection model. The optical model, developed for the fovea,
      appeared to be also suitable for more eccentric locations. The optical densities
      of melanin and of the macular pigments zeaxanthin and lutein peaked in the fovea,
      in correspondence with literature data. The amplitude of the directional
      component, originating in the cone photoreceptors, had its maximum at 1 deg. The
      maximum of the directionality (peakedness) occurred at a slightly higher
      eccentricity.

PMID- 21198170
TI  - Experimental measurement of time-dependent photon scatter for diffuse optical
      tomography.
AB  - Time-resolved measurement of early arriving photons through diffusive media has
      been shown to effectively reduce the high degree of light scatter in biological
      tissue. However, the experimentally achievable reduction in photon scatter and
      the impact of time-gated detection on instrument noise performance is not well
      understood. We measure time-dependent photon density sensitivity functions
      (PDSFs) between a pulsed laser source and a photomultiplier tube operating in
      time-correlated single-photon-counting mode. Our data show that with our system,
      measurement of early arriving photons reduces the full width half maximum of
      PDSFs on average by about 40 to 60% versus quasicontinuous wave photons over a
      range of experimental conditions similar to those encountered in small animal
      tomography, corresponding to a 64 to 84% reduction in PDSF volume. Factoring in
      noise considerations, the optimal operating point of our instrument is determined
      to be about the 10% point on the rising edge of the transmitted intensity curve.
      Time-dependent Monte Carlo simulations and the time-resolved diffusion
      approximation are used to model photon propagation and are evaluated for
      agreement with experimental data.

PMID- 21198171
TI  - New mainstream double-end carbon dioxide capnograph for human respiration.
AB  - Most of the current respiratory devices for monitoring CO(2) concentration use
      the side-stream structure. In this work, we engage to design a new double-end
      mainstream device for monitoring CO(2) concentration of gas breathed out of the
      human body. The device can accurately monitor the cardiopulmonary status during
      anesthesia and mechanical ventilation in real time. Meanwhile, to decrease the
      negative influence of device noise and the low sample precision caused by
      temperature drift, wavelet packet denoising and temperature drift compensation
      are used. The new capnograph is proven by clinical trials to be helpful in
      improving the accuracy of capnography.

PMID- 21198172
TI  - Infrared skin damage thresholds from 1940-nm continuous-wave laser exposures.
AB  - A series of experiments are conducted in vivo using Yucatan mini-pigs (Sus scrofa
      domestica) to determine thermal damage thresholds to the skin from 1940-nm
      continuous-wave thulium fiber laser irradiation. Experiments employ exposure
      durations from 10 ms to 10 s and beam diameters of approximately 4.8 to 18 mm.
      Thermal imagery data provide a time-dependent surface temperature response from
      the laser. A damage endpoint of minimally visible effect is employed to determine
      threshold for damage at 1 and 24 h postexposure. Predicted thermal response and
      damage thresholds are compared with a numerical model of optical-thermal
      interaction. Results are compared with current exposure limits for laser safety.
      It is concluded that exposure limits should be based on data representative of
      large-beam exposures, where effects of radial diffusion are minimized for longer
      duration damage thresholds.

PMID- 21198173
TI  - Boundary integral method for simulating laser short-pulse penetration into
      biological tissues.
AB  - The study of short-pulse propagation through biological tissues is important due
      to the medical applications of short-pulse lasers. Techniques used for numerical
      study of short pulses through human tissues include the Monte Carlo (MC) method,
      the finite-element method, and the finite-difference time-domain (FDTD), but
      these are often time consuming. Recently, the boundary integral method (BIM) was
      applied to overcome this problem. The literature shows that the BIM is faster
      than the other mentioned methods. We first investigate the precision of results
      obtained by the BIM by comparison with those results obtained by the MC and FDTD
      methods. Then we use the BIM to investigate the short-pulse penetration into
      biological tissues. We also study the effects of optical properties of tissues
      such as scattering, the absorption coefficient, the anisotropic factor on the
      penetrating pulse. We also, consider the propagation of pulses emitted from
      extended sources with different temporal evolutions.

PMID- 21198174
TI  - Optical trapping of spermatozoa using Laguerre-Gaussian laser modes.
AB  - We report results of a study on the use of Laguerre-Gaussian (LG) modes for
      optical trapping of spermatozoa. The results show that for a given trap beam
      power the first-order LG mode (LG(01)) leads to lower photodamage to the cells
      without compromising the trapping efficiency.

PMID- 21198175
TI  - Identification of different bacterial species in biofilms using confocal Raman
      microscopy.
AB  - Confocal Raman microspectroscopy is used to discriminate between different
      species of bacteria grown in biofilms. Tests are performed using two bacterial
      species, Streptococcus sanguinis and Streptococcus mutans, which are major
      components of oral plaque and of particular interest due to their association
      with healthy and cariogenic plaque, respectively. Dehydrated biofilms of these
      species are studied as a simplified model of dental plaque. A prediction model
      based on principal component analysis and logistic regression is calibrated using
      pure biofilms of each species and validated on pure biofilms grown months later,
      achieving 96% accuracy in prospective classification. When biofilms of the two
      species are partially mixed together, Raman-based identifications are achieved
      within ~2 MUm of the boundaries between species with 97% accuracy. This
      combination of spatial resolution and predication accuracy should be suitable for
      forming images of species distributions within intact two-species biofilms.

PMID- 21198176
TI  - Method to reconstruct neuronal action potential train from two-photon calcium
      imaging.
AB  - Identification of a small population of neuronal action potentials (APs) firing
      is considered essential to discover the operating principles of neuronal
      circuits. A promising method is to indirectly monitor the AP discharges in
      neurons from the recordings their intracellular calcium fluorescence transients.
      However, it is hard to reveal the nonlinear relationship between neuronal calcium
      fluorescence transients and the corresponding AP burst discharging. We propose a
      method to reconstruct the neuronal AP train from calcium fluorescence
      diversifications based on a multiscale filter and a convolution operation.
      Results of experimental data processing show that the false-positive rate and the
      event detection rate are about 10 and 90%, respectively. Meanwhile, the APs
      firing at a high frequency up to 40 Hz can also be successfully identified. From
      the results, it can be concluded that the method has strong power to reconstruct
      a neuronal AP train from a burst firing.

PMID- 21198177
TI  - Scattering attenuation microscopy of oral epithelial dysplasia.
AB  - We present a new method for quantitative visualization of premalignant oral
      epithelium called scattering attenuation microscopy (SAM). Using low-coherence
      interferometry, SAM projects measurements of epithelial optical attenuation onto
      an image of the tissue surface as a color map. The measured attenuation is
      dominated by optical scattering that provides a metric of the severity of oral
      epithelial dysplasia (OED). Scattering is sensitive to the changes in size and
      distribution of nuclear material that are characteristic of OED, a condition
      recognized by the occurrence of basal-cell-like features throughout the
      epithelial depth. SAM measures the axial intensity change of light backscattered
      from epithelial tissue. Scattering measurements are obtained from sequential
      axial scans of a 3-D tissue volume and displayed as a 2-D SAM image. A novel
      segmentation method is used to confine scattering measurement to epithelial
      tissue. This is applied to oral biopsy samples obtained from 19 patients. Our
      results show that imaging of tissue scattering can be used to discriminate
      between different dysplastic severities and furthermore presents a powerful tool
      for identifying the most representative tissue site for biopsy.

PMID- 21198178
TI  - Adaptive optics multiphoton microscopy to study ex vivo ocular tissues.
AB  - We develop an adaptive optics (AO) multiphoton microscope by incorporating a
      deformable mirror and a Hartmann-Shack wavefront sensor. The AO module operating
      in closed-loop is used to correct for the aberrations of the illumination laser
      beam. This increases the efficiency of the nonlinear processes in reducing tissue
      photodamage, improves contrast, and enhances lateral resolution in images of
      nonstained ocular tissues. In particular, the use of AO in the multiphoton
      microscope provides a better visualization of ocular structures, which are
      relevant in ophthalmology. This instrument might be useful to explore the
      possible connections between changes in ocular structures and the associated
      pathologies.

PMID- 21198179
TI  - Localization capability and limitation of electron-multiplying charge-coupled,
      scientific complementary metal-oxide semiconductor, and charge-coupled devices
      for superresolution imaging.
AB  - Localization of a single fluorescent molecule is required in a number of
      superresolution imaging techniques for visualizing biological structures at
      cellular and subcellular levels. The localization capability and limitation of
      low-light detectors are critical for such a purpose. We present an updated
      evaluation on the performance of three typical low-light detectors, including a
      popular electron-multiplying CCD (EMCCD), a newly developed scientific CMOS
      (sCMOS), and a representative cooled CCD, for superresolution imaging. We find
      that under some experimental accessible conditions, the sCMOS camera shows a
      competitive and even better performance than the EMCCD camera, which has long
      been considered the detector of choice in the field of superresolution imaging.

PMID- 21198180
TI  - Spectral Doppler optical coherence tomography imaging of localized ischemic
      stroke in a mouse model.
AB  - We report the use of spectral Doppler optical coherence tomography imaging
      (SDOCTI) for quantitative evaluation of dynamic blood circulation before and
      after a localized ischemic stroke in a mouse model. Rose Bengal photodynamic
      therapy (PDT) is used as a noninvasive means for inducing localized ischemia in
      cortical microvasculature of the mouse. Fast, repeated Doppler optical coherence
      tomography scans across vessels of interest are performed to record flow dynamic
      information with high temporal resolution. Doppler-angle-independent flow indices
      are used to quantify vascular conditions before and after the induced ischemia by
      the photocoagulation of PDT. The higher (or lower) flow resistive indices are
      associated with higher (or lower) resistance states that are confirmed by laser
      speckle flow index maps (of laser speckle imaging). Our in vivo experiments shows
      that SDOCTI can provide complementary quantified flow information that is an
      alternative to blood volume measurement, and can be used as a means for cortical
      microvasculature imaging well suited for small animal studies.

PMID- 21198181
TI  - Imaging heterogeneous absorption distribution of advanced breast cancer by
      optical tomography.
AB  - Tumor vascular patterns of advanced breast cancers are complex and heterogeneous.
      Two typical light absorption patterns of periphery enhancement and posterior
      shadowing have been observed when imaging these advanced cancers using optical
      tomography guided by ultrasound. We perform a series simulation and phantom
      experiments to systemically evaluate the effects of target parameters, target
      locations, and target optical properties on imaging periphery enhancement
      absorption distribution using reflection geometry. Large tumors are modeled as
      concentric semiellipsoidal targets of different outer shell and inner core
      optical properties. We show that larger targets of more than 3 to 4 cm diameter
      with outer shell thicknesses less than 1 cm can be resolved at a depth less than
      3 cm. A clinical example is given to show the complex vasculature distributions
      seen from an advanced cancer.

PMID- 21198182
TI  - Nonlinear microscopy of lipid storage and fibrosis in muscle and liver tissues of
      mice fed high-fat diets.
AB  - Hallmarks of high-fat Western diet intake, such as excessive lipid accumulation
      in skeletal muscle and liver as well as liver fibrosis, are investigated in
      tissues from mice using nonlinear microscopy, second harmonic generation (SHG),
      and coherent anti-Stokes Raman scattering (CARS), supported by conventional
      analysis methods. Two aspects are presented; intake of standard chow versus
      Western diet, and a comparison between two high-fat Western diets of different
      polyunsaturated lipid content. CARS microscopy images of intramyocellular lipid
      droplets in muscle tissue show an increased amount for Western diet compared to
      standard diet samples. Even stronger diet impact is found for liver samples,
      where combined CARS and SHG microscopy visualize clear differences in lipid
      content and collagen fiber development, the latter indicating nonalcoholic fatty
      liver disease (NAFLD) and steatohepatitis induced at a relatively early stage for
      Western diet. Characteristic for NAFLD, the fibrous tissue-containing lipids
      accumulate in larger structures. This is also observed in CARS images of liver
      samples from two Western-type diets of different polyunsaturated lipid contents.
      In summary, nonlinear microscopy has strong potential (further promoted by
      technical advances toward clinical use) for detection and characterization of
      steatohepatitis already in its early stages.

PMID- 21198183
TI  - Accelerating frequency-domain diffuse optical tomographic image reconstruction
      using graphics processing units.
AB  - Diffuse optical tomographic image reconstruction uses advanced numerical models
      that are computationally costly to be implemented in the real time. The graphics
      processing units (GPUs) offer desktop massive parallelization that can accelerate
      these computations. An open-source GPU-accelerated linear algebra library package
      is used to compute the most intensive matrix-matrix calculations and matrix
      decompositions that are used in solving the system of linear equations. These
      open-source functions were integrated into the existing frequency-domain diffuse
      optical image reconstruction algorithms to evaluate the acceleration capability
      of the GPUs (NVIDIA Tesla C 1060) with increasing reconstruction problem sizes.
      These studies indicate that single precision computations are sufficient for
      diffuse optical tomographic image reconstruction. The acceleration per iteration
      can be up to 40, using GPUs compared to traditional CPUs in case of three
      dimensional reconstruction, where the reconstruction problem is more
      underdetermined, making the GPUs more attractive in the clinical settings. The
      current limitation of these GPUs in the available onboard memory (4 GB) that
      restricts the reconstruction of a large set of optical parameters, more than
      13,377.

PMID- 21198184
TI  - Simultaneous spatial and spectral mapping of flow using photoacoustic Doppler
      measurement.
AB  - We demonstrate the use of tone-burst excitation and time-gated spectral analysis
      for photoacoustic Doppler mapping of flow in an unperturbed vessel phantom and in
      a vessel with a spatially varying lumen. The method, which mimics pulsed Doppler
      ultrasound, enables simultaneous measurement of axial position and flow as well
      as complete characterization of the Doppler spectrum over a wide range of mean
      velocities (3.5 to 200 mm/s). To generate the required optical excitation, a
      continuous cw laser source followed by an external electro-optic modulator is
      used. Stenoses at various levels are emulated in a C-flex tube with a flowing
      suspension of micrometer-scale carbon particles. Two-dimensional maps of spectral
      content versus axial position at different points along the vessel and for
      various levels of perturbations demonstrate the potential use of the method for
      characterization of flow irregularities.

PMID- 21198185
TI  - Analysis and three-dimensional visualization of collagen in artificial scaffolds
      using nonlinear microscopy techniques.
AB  - Extracellularly distributed collagen and chondrocytes seeded in gelatine and poly
      E-caprolactone scaffolds are visualized by two-photon excitation microscopy
      (TPEM) and second-harmonic generation (SHG) imaging in both forward and backward
      nondescanned modes. Joint application of TPEM and SHG imaging in combination with
      stereological measurements of collagen enables us not only to take high
      resolution 3-D images, but also to quantitatively analyze the collagen volume and
      a spatial arrangement of cell-collagen-scaffold systems, which was previously
      impossible. This novel approach represents a powerful tool for the analysis of
      collagen-containing scaffolds with applications in cartilage tissue engineering.

PMID- 21198186
TI  - Enhancing magnetic resonance imaging tumor detection with fluorescence intensity
      and lifetime imaging.
AB  - Early detection is important for many solid cancers but the images provided by
      ultrasound, magnetic resonance imaging (MRI), and computed tomography applied
      alone or together, are often not sufficient for decisive early screening /
      diagnosis. We demonstrate that MRI augmented with fluorescence intensity (FI)
      substantially improves detection. Early stage murine pancreatic tumors that could
      not be identified by blinded, skilled observers using MRI alone, were easily
      identified with MRI along with FI images acquired with photomultiplier tube
      detection and offset laser scanning. Moreover, we show that fluorescence lifetime
      (FLT) imaging enables positive identification of the labeling fluorophore and
      discriminates it from surrounding tissue autofluorescence. Our data suggest
      combined-modality imaging with MRI, FI, and FLT can be used to screen and
      diagnose early tumors.

PMID- 21198187
TI  - Quantitative measurement of attenuation coefficients of bladder biopsies using
      optical coherence tomography for grading urothelial carcinoma of the bladder.
AB  - Real-time grading of bladder urothelial carcinoma (UC) is clinically important,
      but the current standard for grading (histopathology) cannot provide this
      information. Based on optical coherence tomography (OCT)-measured optical
      attenuation (MU(t)), the grade of bladder UC could potentially be assessed in
      real time. We evaluate ex vivo whether MU(t) differs between different grades of
      UC and benign bladder tissue. Human bladder tissue specimens are examined ex vivo
      by 850-nm OCT using dynamic focusing. Three observers independently determine the
      MU(t) from the OCT images, and three pathologists independently review the
      corresponding histology slides. For both methods, a consensus diagnosis is made.
      We include 76 OCT scans from 54 bladder samples obtained in 20 procedures on 18
      patients. The median (interquartile range) MU(t) of benign tissue is 5.75 mm(-1)
      (4.77 to 6.14) versus 5.52 mm(-1) (3.47 to 5.90), 4.85 mm(-1) (4.25 to 6.50), and
      5.62 mm(-1) (5.01 to 6.29) for grade 1, 2, and 3 UC, respectively (p = 0.732).
      Interobserver agreement of histopathology is "substantial" [Kappa 0.62, 95%
      confidence interval (IC) 0.54 to 0.70] compared to "almost perfect" [interclass
      correlation coefficient (ICC) 0.87, 95% CI 0.80 to 0.92] for OCT. Quantitative
      OCT analysis (by MU(t)) does not detect morphological UC changes. This may be due
      to factors typical for an ex-vivo experimental setting.

PMID- 21198188
TI  - Endoscopic low-coherence topography measurement for upper airways and hollow
      samples.
AB  - To evaluate the severity of airway pathologies, quantitative dimensioning of
      airways is of utmost importance. Endoscopic vision gives a projective image and
      thus no true scaling information can be directly deduced from it. In this
      article, an approach based on an interferometric setup, a low-coherence laser
      source and a standard rigid endoscope is presented, and applied to hollow samples
      measurements. More generally, the use of the low-coherence interferometric setup
      detailed here could be extended to any other endoscopy-related field of interest,
      e.g., gastroscopy, arthroscopy and other medical or industrial applications where
      tri-dimensional topology is required. The setup design with a multiple fibers
      illumination system is presented. Demonstration of the method ability to operate
      on biological samples is assessed through measurements on ex vivo pig bronchi.

PMID- 21198189
TI  - Evaluation of linear discriminant analysis for automated Raman histological
      mapping of esophageal high-grade dysplasia.
AB  - Rapid Raman mapping has the potential to be used for automated histopathology
      diagnosis, providing an adjunct technique to histology diagnosis. The aim of this
      work is to evaluate the feasibility of automated and objective pathology
      classification of Raman maps using linear discriminant analysis. Raman maps of
      esophageal tissue sections are acquired. Principal component (PC)-fed linear
      discriminant analysis (LDA) is carried out using subsets of the Raman map data
      (6483 spectra). An overall (validated) training classification model performance
      of 97.7% (sensitivity 95.0 to 100% and specificity 98.6 to 100%) is obtained. The
      remainder of the map spectra (131,672 spectra) are projected onto the
      classification model resulting in Raman images, demonstrating good correlation
      with contiguous hematoxylin and eosin (HE) sections. Initial results suggest that
      LDA has the potential to automate pathology diagnosis of esophageal Raman images,
      but since the classification of test spectra is forced into existing training
      groups, further work is required to optimize the training model. A small pixel
      size is advantageous for developing the training datasets using mapping data,
      despite lengthy mapping times, due to additional morphological information
      gained, and could facilitate differentiation of further tissue groups, such as
      the basal cells/lamina propria, in the future, but larger pixels sizes (and
      faster mapping) may be more feasible for clinical application.

PMID- 21198190
TI  - Label-free imaging of biomolecules in food products using stimulated Raman
      microscopy.
AB  - The development of methods that allow microscale studies of complex biomaterials
      based on their molecular composition is of great interest to a wide range of
      research fields. We show that stimulated Raman scattering (SRS) microscopy is an
      excellent analytical tool to study distributions of different biomolecules in
      multiphasic systems. SRS combines the label-free molecular specificity of
      vibrational spectroscopy with an enhanced sensitivity due to coherent excitation
      of molecular vibrations. Compared to previous imaging studies using coherent anti
      Stokes Raman scattering microscopy, the main advantage of SRS microscopy is the
      absence of the unwanted nonresonant background, which translates into a superior
      sensitivity and undistorted vibrational spectra. We compare spectra of complex
      materials obtained with stimulated Raman scattering and spontaneous Raman
      scattering in the crowded fingerprint region. We find that, as expected, there is
      excellent correspondence and that the SRS spectra are free from interference from
      background fluorescence. In addition, we show high-resolution imaging of the
      distributions of selected biomolecules, such as lipids and proteins, in food
      products with SRS microscopy.

PMID- 21198191
TI  - Comparison of multispectral wide-field optical imaging modalities to maximize
      image contrast for objective discrimination of oral neoplasia.
AB  - Multispectral widefield optical imaging has the potential to improve early
      detection of oral cancer. The appropriate selection of illumination and
      collection conditions is required to maximize diagnostic ability. The goals of
      this study were to (i) evaluate image contrast between oral cancer/precancer and
      non-neoplastic mucosa for a variety of imaging modalities and
      illumination/collection conditions, and (ii) use classification algorithms to
      evaluate and compare the diagnostic utility of these modalities to discriminate
      cancers and precancers from normal tissue. Narrowband reflectance,
      autofluorescence, and polarized reflectance images were obtained from 61 patients
      and 11 normal volunteers. Image contrast was compared to identify modalities and
      conditions yielding greatest contrast. Image features were extracted and used to
      train and evaluate classification algorithms to discriminate tissue as non
      neoplastic, dysplastic, or cancer; results were compared to histologic diagnosis.
      Autofluorescence imaging at 405-nm excitation provided the greatest image
      contrast, and the ratio of red-to-green fluorescence intensity computed from
      these images provided the best classification of dysplasia/cancer versus non
      neoplastic tissue. A sensitivity of 100% and a specificity of 85% were achieved
      in the validation set. Multispectral widefield images can accurately distinguish
      neoplastic and non-neoplastic tissue; however, the ability to separate
      precancerous lesions from cancers with this technique was limited.

PMID- 21198192
TI  - Spectral hole burning for ultrasound-modulated optical tomography of thick
      tissue.
AB  - We apply spectral hole burning (SHB)-aided detection in ultrasound-modulated
      optical tomography (UOT) to image optical heterogeneities in thick tissue
      mimicking phantom samples and chicken breast tissue. The efficiency of SHB is
      improved by using a Tm(3+):YAG crystal of higher doping concentration (2.0
      atomic%) and a double-pass pumping configuration, in which the pump beam is
      transmitted through the crystal twice to burn a deeper spectral hole with the
      available optical intensity. With the improved SHB-UOT system, we image
      absorbing, scattering, and phase objects that are embedded in the middle plane of
      a 30-mm-thick phantom sample. The imaging resolution was 0.5 mm in the lateral
      direction, as defined by the focal width of the ultrasonic transducer, and 1.5 mm
      in the axial direction, as determined by the ultrasonic burst length. We also
      image two absorbing objects embedded in a 32-mm-thick chicken breast sample. The
      results suggest that the improved SHB-UOT system is one step closer to the
      practical optical imaging application in biological and clinical studies.

PMID- 21198193
TI  - Automated classification of breast pathology using local measures of broadband
      reflectance.
AB  - We demonstrate that morphological features pertinent to a tissue's pathology may
      be ascertained from localized measures of broadband reflectance, with a
      mesoscopic resolution (100-MUm lateral spot size) that permits scanning of an
      entire margin for residual disease. The technical aspects and optimization of a k
      nearest neighbor classifier for automated diagnosis of pathologies are presented,
      and its efficacy is validated in 29 breast tissue specimens. When discriminating
      between benign and malignant pathologies, a sensitivity and specificity of 91 and
      77% was achieved. Furthermore, detailed subtissue-type analysis was performed to
      consider how diverse pathologies influence scattering response and overall
      classification efficacy. The increased sensitivity of this technique may render
      it useful to guide the surgeon or pathologist where to sample pathology for
      microscopic assessment.

PMID- 21198194
TI  - Computer-aided interpretation approach for optical tomographic images.
AB  - A computer-aided interpretation approach is proposed to detect rheumatic
      arthritis (RA) in human finger joints using optical tomographic images. The image
      interpretation method employs a classification algorithm that makes use of a so
      called self-organizing mapping scheme to classify fingers as either affected or
      unaffected by RA. Unlike in previous studies, this allows for combining multiple
      image features, such as minimum and maximum values of the absorption coefficient
      for identifying affected and not affected joints. Classification performances
      obtained by the proposed method were evaluated in terms of sensitivity,
      specificity, Youden index, and mutual information. Different methods (i.e.,
      clinical diagnostics, ultrasound imaging, magnet resonance imaging, and
      inspection of optical tomographic images), were used to produce ground truth
      benchmarks to determine the performance of image interpretations. Using data from
      100 finger joints, findings suggest that some parameter combinations lead to
      higher sensitivities, while others to higher specificities when compared to
      single parameter classifications employed in previous studies. Maximum
      performances are reached when combining the minimum/maximum ratio of the
      absorption coefficient and image variance. In this case, sensitivities and
      specificities over 0.9 can be achieved. These values are much higher than values
      obtained when only single parameter classifications were used, where
      sensitivities and specificities remained well below 0.8.

PMID- 21198195
TI  - Optical imaging of tumor hypoxia dynamics.
AB  - The influence of the tumor microenvironment and hypoxia plays a significant role
      in determining cancer progression, treatment response, and treatment resistance.
      That the tumor microenvironment is highly heterogeneous with significant
      intratumor and intertumor variability presents a significant challenge in
      developing effective cancer therapies. Critical to understanding the role of the
      tumor microenvironment is the ability to dynamically quantify oxygen levels in
      the vasculature and tissue in order to elucidate the roles of oxygen supply and
      consumption, spatially and temporally. To this end, we describe the use of
      hyperspectral imaging to characterize hemoglobin absorption to quantify
      hemoglobin content and oxygen saturation, as well as dual emissive
      fluorescent/phosphorescent boron nanoparticles, which serve as ratiometric
      indicators of tissue oxygen tension. Applying these techniques to a window
      chamber tumor model illustrates the role of fluctuations in hemoglobin saturation
      in driving changes in tissue oxygenation, the two being significantly correlated
      (r = 0.77). Finally, a green-fluorescence-protein reporter for hypoxia inducible
      factor-1 (HIF-1) provides an endpoint for hypoxic stress in the tumor, which is
      used to demonstrate a significant association between tumor hypoxia dynamics and
      HIF-1 activity in an in vivo demonstration of the technique.

PMID- 21198196
TI  - Measuring hemodynamics in the developing heart tube with four-dimensional gated
      Doppler optical coherence tomography.
AB  - Hemodynamics is thought to play a major role in heart development, yet tools to
      quantitatively assess hemodynamics in the embryo are sorely lacking. The
      especially challenging analysis of hemodynamics in the early embryo requires new
      technology. Small changes in blood flow could indicate when anomalies are
      initiated even before structural changes can be detected. Furthermore, small
      changes in the early embryo that affect blood flow could lead to profound
      abnormalities at later stages. We present a demonstration of 4-D Doppler optical
      coherence tomography (OCT) imaging of structure and flow, and present several new
      hemodynamic measurements on embryonic avian hearts at early stages prior to the
      formation of the four chambers. Using 4-D data, pulsed Doppler measurements could
      accurately be attained in the inflow and outflow of the heart tube. Also, by
      employing an en-face slice from the 4-D Doppler image set, measurements of stroke
      volume and cardiac output are obtained without the need to determine absolute
      velocity. Finally, an image plane orthogonal to the blood flow is used to
      determine shear stress by calculating the velocity gradient normal to the
      endocardium. Hemodynamic measurements will be crucial to identifying genetic and
      environmental factors that lead to congenital heart defects.

PMID- 21198197
TI  - Anatomy-driven design of a prototype video laryngoscope for extremely low birth
      weight infants.
AB  - Extremely low birth weight (ELBW) infants frequently require endotracheal
      intubation for assisted ventilation or as a route for administration of drugs or
      exogenous surfactant. In adults and less premature infants, the risks of this
      intubation can be greatly reduced using video laryngoscopy, but current products
      are too large and incorrectly shaped to visualize an ELBW infant's airway
      anatomy. We design and prototype a video laryngoscope using a miniature camera
      set in a curved acrylic blade with a 3*6-mm cross section at the tip. The blade
      provides a mechanical structure for stabilizing the tongue and acts as a light
      guide for an LED light source, located remotely to avoid excessive local heating
      at the tip. The prototype is tested on an infant manikin and found to provide
      sufficient image quality and mechanical properties to facilitate intubation.
      Finally, we show a design for a neonate laryngoscope incorporating a wafer-level
      microcamera that further reduces the tip cross section and offers the potential
      for low cost manufacture.

PMID- 21198198
TI  - Current concepts and future perspectives on surgical optical imaging in cancer.
AB  - There are vibrant developments of optical imaging systems and contrast-enhancing
      methods that are geared to enhancing surgical vision and the outcome of surgical
      procedures. Such optical technologies designed for intraoperative use can offer
      high integration in the operating room compared to conventional radiological
      modalities adapted to intraoperative applications. Simple fluorescence epi
      illumination imaging, in particular, appears attractive but may lead to
      inaccurate observations due to the complex nature of photon-tissue interaction.
      Of importance therefore are emerging methods that account for the background
      optical property variation in tissues and can offer accurate, quantitative
      imaging that eliminates the appearance of false negatives or positives. In
      parallel, other nonfluorescent optical imaging methods are summarized and overall
      progress in surgical optical imaging applications is outlined. Key future
      directions that have the potential to shift the paradigm of surgical health care
      are also discussed.

PMID- 21198199
TI  - Optical system based on time-gated, intensified charge-coupled device camera for
      brain imaging studies.
AB  - An imaging system for brain oxygenation based on a time-gated, intensified charge
      coupled device camera was developed. It allows one to image diffusely reflected
      light from an investigated medium at defined time windows delayed with respect to
      the laser pulse. Applying a fast optomechanical switch to deliver the light at a
      wavelength of 780 nm to nine source fibers allowed one to acquire images in times
      as short as 4 s. Thus, the system can be applied in in vivo studies. The system
      was validated in phantom experiments, in which absorbing inclusions were
      localized at different depths and different lateral positions. Then, the decrease
      in absorption of the brain tissue related to increase in oxygenation was
      visualized in the motor cortex area during finger tapping by a healthy volunteer.

PMID- 21198200
TI  - Topographic mapping of subsurface fluorescent structures in tissue using
      multiwavelength excitation.
AB  - Different colors of visible light penetrate to varying depths in tissue due to
      the wavelength dependence of tissue optical absorption and elastic scattering. We
      exploit this to map the contour of the closest surface of a buried fluorescent
      object. This uses a novel algorithm based on the diffusion theory description of
      light propagation in tissue at each excitation wavelength to derive metrics that
      define the depth of the top surface of the object. The algorithm was validated
      using a tissue-simulating phantom. It was then demonstrated in vivo by subsurface
      brain tumor topography in a rodent model, using the fluorescence signal from
      protoporphyrin IX that is preferentially synthesized within malignant cells
      following systemic application of aminolevulinic acid. Comparisons to
      histomorphometry in the brain post mortem show the spatial accuracy of the
      technique. This method has potential for fluorescence image-guided tumor surgery,
      as well as other biomedical and nonbiological applications in subsurface sensing.

PMID- 21198201
TI  - Numerical analysis of gradient index lens-based optical coherence tomography
      imaging probes.
AB  - We report the numerical analysis of gradient index (GRIN) lens-based optical
      coherence tomography imaging probes to derive optimal design parameters. Long and
      short working distance probes with a small focal spot are considered. In each
      model, the working distance and beam waist are characterized and compared for
      different values of length and refractive index of the probe components. We also
      explore the influence of the outer tubing and refractive index of the sample
      media. Numerical results show that the adjustment of the maximum beam diameter
      and focusing angle at the end of the GRIN lens surface is very important for
      determining the optical performance parameters of the probe.

PMID- 21198203
TI  - Long-working-distance fluorescence microscope with high-numerical-aperture
      objectives for variable-magnification imaging in live mice from macro- to
      subcellular.
AB  - We demonstrate the development of a long-working-distance fluorescence microscope
      with high-numerical-aperture objectives for variable-magnification imaging in
      live mice from macro- to subcellular. To observe cytoplasmic and nuclear dynamics
      of cancer cells in the living mouse, 143B human osteosarcoma cells are labeled
      with green fluorescent protein in the nucleus and red fluorescent protein in the
      cytoplasm. These dual-color cells are injected by a vascular route in an
      abdominal skin flap in nude mice. The mice are then imaged with the Olympus MVX10
      macroview fluorescence microscope. With the MVX10, the nuclear and cytoplasmic
      behavior of cancer cells trafficking in blood vessels of live mice is observed.
      We also image lung metastases in live mice from the macro- to the subcellular
      level by opening the chest wall and imaging the exposed lung in live mice.
      Injected splenocytes, expressing cyan fluorescent protein, could also be imaged
      on the lung of live mice. We demonstrate that the MVX10 microscope offers the
      possibility of full-range in vivo fluorescence imaging from macro- to subcellular
      and should enable widespread use of powerful imaging technologies enabled by
      genetic reporters and other fluorophores.

PMID- 21198202
TI  - Nanoscale nuclear architecture for cancer diagnosis beyond pathology via spatial
      domain low-coherence quantitative phase microscopy.
AB  - Definitive diagnosis of malignancy is often challenging due to limited
      availability of human cell or tissue samples and morphological similarity with
      certain benign conditions. Our recently developed novel technology-spatial-domain
      low-coherence quantitative phase microscopy (SL-QPM)-overcomes the technical
      difficulties and enables us to obtain quantitative information about cell nuclear
      architectural characteristics with nanoscale sensitivity. We explore its ability
      to improve the identification of malignancy, especially in cytopathologically non
      cancerous-appearing cells. We perform proof-of-concept experiments with an animal
      model of colorectal carcinogenesis-APC(Min) mouse model and human cytology
      specimens of colorectal cancer. We show the ability of in situ nanoscale nuclear
      architectural characteristics in identifying cancerous cells, especially in those
      labeled as "indeterminate or normal" by expert cytopathologists. Our approach is
      based on the quantitative analysis of the cell nucleus on the original cytology
      slides without additional processing, which can be readily applied in a
      conventional clinical setting. Our simple and practical optical microscopy
      technique may lead to the development of novel methods for early detection of
      cancer.

PMID- 21198204
TI  - Laser speckle contrast imaging of cerebral blood flow in humans during
      neurosurgery: a pilot clinical study.
AB  - Monitoring cerebral blood flow (CBF) during neurosurgery can provide important
      physiological information for a variety of surgical procedures. CBF measurements
      are important for assessing whether blood flow has returned to presurgical
      baseline levels and for assessing postsurgical tissue viability. Existing
      techniques for intraoperative monitoring of CBF based on magnetic resonance
      imaging are expensive and often impractical, while techniques such as indocyanine
      green angiography cannot produce quantitative measures of blood flow. Laser
      speckle contrast imaging (LSCI) is an optical technique that has been widely used
      to quantitatively image relative CBF in animal models in vivo. In a pilot
      clinical study, we adapted an existing neurosurgical operating microscope to
      obtain LSCI images in humans in real time during neurosurgery under baseline
      conditions and after bipolar cautery. Simultaneously recorded ECG waveforms from
      the patient were used to develop a filter that helped reduce measurement
      variabilities due to motion artifacts. Results from this study demonstrate the
      feasibility of using LSCI to obtain blood flow images during neurosurgeries and
      its capability to produce full field CBF image maps with excellent spatial
      resolution in real-time with minimal disruption to the surgical procedure.

PMID- 21198206
TI  - Near-infrared spectroscopic applications for diagnosis of endometrial carcinoma.
AB  - NIR spectra of 77 endometrium sections (malignant, hyperplasia, and normal
      samples) are collected. Partial least squares discriminant analysis (PLS-DA) and
      fuzzy rule-building expert systems (FuRES) are used for classification based on
      the NIR spectral data. The classification ability of two classifiers is evaluated
      by using ten bootstraps and five Latin partitions. The results indicate that the
      classification ability of FuRES is better than that of PLS-DA. The sensitivity,
      specificity, and accuracy obtained from FuRES for malignant endometrium diagnosis
      are 90.0+/-0.7, 95.0+/-0.8, and 93.1+/-0.8%, respectively. The results
      demonstrate that NIR spectroscopy combined with the FuRES technique is promising
      for the classification of endometrial specimens and for practical diagnostic
      applications.

PMID- 21198205
TI  - Forster resonance energy transfer as a tool to study photoreceptor biology.
AB  - Vision is initiated in photoreceptor cells of the retina by a set of biochemical
      events called phototransduction. These events occur via coordinated dynamic
      processes that include changes in secondary messenger concentrations,
      conformational changes and post-translational modifications of signaling
      proteins, and protein-protein interactions between signaling partners. A complete
      description of the orchestration of these dynamic processes is still unavailable.
      Described in this work is the first step in the development of tools combining
      fluorescent protein technology, Forster resonance energy transfer (FRET), and
      transgenic animals that have the potential to reveal important molecular insights
      about the dynamic processes occurring in photoreceptor cells. We characterize the
      fluorescent proteins SCFP3A and SYFP2 for use as a donor-acceptor pair in FRET
      assays, which will facilitate the visualization of dynamic processes in living
      cells. We also demonstrate the targeted expression of these fluorescent proteins
      to the rod photoreceptor cells of Xenopus laevis, and describe a general method
      for detecting FRET in these cells. The general approaches described here can
      address numerous types of questions related to phototransduction and
      photoreceptor biology by providing a platform to visualize dynamic processes in
      molecular detail within a native context.

PMID- 21198207
TI  - Infrared spectroscopy reveals both qualitative and quantitative differences in
      equine subchondral bone during maturation.
AB  - The collagen phase in bone is known to undergo major changes during growth and
      maturation. The objective of this study is to clarify whether Fourier transform
      infrared (FTIR) microspectroscopy, coupled with cluster analysis, can detect
      quantitative and qualitative changes in the collagen matrix of subchondral bone
      in horses during maturation and growth. Equine subchondral bone samples (n = 29)
      from the proximal joint surface of the first phalanx are prepared from two sites
      subjected to different loading conditions. Three age groups are studied: newborn
      (0 days old), immature (5 to 11 months old), and adult (6 to 10 years old)
      horses. Spatial collagen content and collagen cross-link ratio are quantified
      from the spectra. Additionally, normalized second derivative spectra of samples
      are clustered using the k-means clustering algorithm. In quantitative analysis,
      collagen content in the subchondral bone increases rapidly between the newborn
      and immature horses. The collagen cross-link ratio increases significantly with
      age. In qualitative analysis, clustering is able to separate newborn and adult
      samples into two different groups. The immature samples display some
      nonhomogeneity. In conclusion, this is the first study showing that FTIR spectral
      imaging combined with clustering techniques can detect quantitative and
      qualitative changes in the collagen matrix of subchondral bone during growth and
      maturation.

PMID- 21198208
TI  - Comparison of sorting algorithms to increase the range of Hartmann-Shack
      aberrometry.
AB  - Recently many software-based approaches have been suggested for improving the
      range and accuracy of Hartmann-Shack aberrometry. We compare the performance of
      four representative algorithms, with a focus on aberrometry for the human eye.
      Algorithms vary in complexity from the simplistic traditional approach to
      iterative spline extrapolation based on prior spot measurements. Range is
      assessed for a variety of aberration types in isolation using computer modeling,
      and also for complex wavefront shapes using a real adaptive optics system. The
      effects of common sources of error for ocular wavefront sensing are explored. The
      results show that the simplest possible iterative algorithm produces comparable
      range and robustness compared to the more complicated algorithms, while keeping
      processing time minimal to afford real-time analysis.

PMID- 21198210
TI  - Quantification of in vivo fluorescence decoupled from the effects of tissue
      optical properties using fiber-optic spectroscopy measurements.
AB  - We present a method for tissue fluorescence quantification in situ using a
      handheld fiber optic probe that measures both the fluorescence and diffuse
      reflectance spectra. A simplified method to decouple the fluorescence spectrum
      from distorting effects of the tissue optical absorption and scattering is
      developed, with the objective of accurately quantifying the fluorescence in
      absolute units. The primary motivation is measurement of 5-aminolevulinic acid
      induced protoporphyrin IX (ALA-PpIX) concentration in tissue during fluorescence
      guided resection of malignant brain tumors. This technique is validated in
      phantoms and ex vivo mouse tissues, and tested in vivo in a rabbit brain tumor
      model using ALA-PpIX fluorescence contrast.

PMID- 21198209
TI  - Development of combination tapered fiber-optic biosensor dip probe for
      quantitative estimation of interleukin-6 in serum samples.
AB  - A combination tapered fiber-optic biosensor (CTFOB) dip probe for rapid and cost
      effective quantification of proteins in serum samples has been developed. This
      device relies on diode laser excitation and a charged-coupled device spectrometer
      and functions on a technique of sandwich immunoassay. As a proof of principle,
      this technique was applied in a quantitative estimation of interleukin IL-6. The
      probes detected IL-6 at picomolar levels in serum samples obtained from a patient
      with lupus, an autoimmune disease, and a patient with lymphoma. The estimated
      concentration of IL-6 in the lupus sample was 5.9 +/- 0.6 pM, and in the lymphoma
      sample, it was below the detection limit. These concentrations were verified by a
      procedure involving bead-based xMAP technology. A similar trend in the
      concentrations was observed. The specificity of the CTFOB dip probes was assessed
      by analysis with receiver operating characteristics. This analysis suggests that
      the dip probes can detect 5-pM or higher concentration of IL-6 in these samples
      with specificities of 100%. The results provide information for guiding further
      studies in the utilization of these probes to quantify other analytes in body
      fluids with high specificity and sensitivity.

PMID- 21198211
TI  - Evaluation of high-performance liquid chromatography laser-induced fluorescence
      for serum protein profiling for early diagnosis of oral cancer.
AB  - The present work deals with the evaluation of a high-performance liquid
      chromatography laser-induced fluorescence (HPLC-LIF) technique developed in our
      laboratory for early detection of oral cancer from protein profiles of body
      fluids. The results show that protein profiles of serum samples from a given
      class of samples, say, normal, premalignant, or malignant, are statistically very
      close to each other, while profiles of members of any class are significantly
      different from other classes. The performance of the technique is evaluated by
      the use of sensitivity and specificity pairs, receiver operating characteristic
      (ROC) analysis, and Youden's Index. The technique uses protein profile
      differences in serum samples, registered by the HPLC-LIF technique. The study is
      carried out using serum samples from volunteers diagnosed as normal or
      premalignant clinically, and as malignant by histopathology. The specificities
      and sensitivities of the HPLC-LIF method at an ideal threshold (M-distance = 2)
      for normal, malignant, and premalignant classes are 100, 69.5, and 61.5%, and
      86.5, 87.5, and 87.5% respectively.

PMID- 21198212
TI  - Dual-trap Raman tweezers for probing dynamics and heterogeneity of interacting
      microbial cells.
AB  - We report on development of dual-trap Raman tweezers for monitoring cellular
      dynamics and heterogeneity of interacting living cells suspended in a liquid
      medium. Dual-beam optical tweezers were combined with Raman spectroscopy, which
      allows capturing two cells that are in direct contact or closely separated by a
      few micrometers and simultaneously acquiring their Raman spectra with an imaging
      CCD spectrograph. As a demonstration, we recorded time-lapse Raman spectra of
      budding yeast cells held in dual traps for over 40 min to monitor the dynamic
      growth in a nutrient medium. We also monitored two germinating Bacillus spores
      after the initiation with L-alanine and observed their heterogeneity in the
      release of CaDPA under identical microenvironment.

PMID- 21198213
TI  - Evaluation of a novel noncontact spectrally and spatially resolved reflectance
      setup with continuously variable source-detector separation using silicone
      phantoms.
AB  - We present a new variant of a noncontact, oblique incidence spatially resolved
      reflectance setup. The continuously variable source detector separation enables
      adaptation to high and low albedo samples. Absorption (MU(a)) and reduced
      scattering coefficients (MU(') (s)) are determined in the wavelength range of 400
      1000 nm using a lookup table, calculated by a Monte Carlo simulation of the light
      transport. The method is characterized by an silicone phantom study covering a
      wide parameter range 0.01 mm(-1) <= MU(a) <= 2.5 mm(-1) and 0.2 mm(-1) <= MU(')
      (s) <= 10 mm(-1), which includes the optical parameters of tissue in the visible
      and near infrared. The influence of the incident angle and the detection aperture
      on the simulated remission was examined. Using perpendicular incidence and 90-deg
      detection aperture in the Monte Carlo simulation in contrast to the experimental
      situation with 30-deg incidence and 4.6-deg detection aperture is shown to be
      valid for the parameter range MU(') (s) > 1 mm(-1) and MU(a) < 1.2 mm(-1). A Mie
      calculation is presented, showing that a decreasing reduced scattering
      coefficient for increasing absorption can be the consequence of real physics
      instead of cross talk.

PMID- 21198214
TI  - Assessment of thermal coagulation in ex-vivo tissues using Raman spectroscopy.
AB  - Raman spectroscopy is used to study the effects of heating on specific molecular
      bonds present in albumen-based coagulation phantoms and ex-vivo tissues. Thermal
      coagulation is induced by submerging albumen-based phantoms in a 75 degrees C
      water bath to achieve target temperatures of 45, 55, 65, and 75 degrees C. Laser
      photocoagulation is performed on ex-vivo bovine muscle samples, yielding induced
      temperatures between 46 and 90 degrees C, as reported by implanted
      microthermocouples. All phantoms and tissue samples are cooled to room
      temperature, and Raman spectra are acquired at the microthermocouple locations.
      Shifts in major Raman bands are observed with laser heating in bovine muscle,
      specifically from the amide-1 alpha-helix group (~1655 cm(-1)), the CH(2)/CH(3)
      group (~1446 cm(-1)), the Calpha-H stretch group (~1312 cm(-1)), and the CN
      stretch group (~1121cm(-1)). Raman bands at 1334 cm(-1) (tryptophan), 1317 cm(-1)
      [nu(Calpha-H)], and 1655 cm(-1) (amide-1 alpha-helix) also show a decrease in
      intensity following heating. The results suggest that Raman band locations and
      relative intensities are affected by thermal denaturation of proteins, and hence,
      may be a useful tool for monitoring the onset and progression of coagulation
      during thermal therapies.

PMID- 21198215
TI  - Immunohistochemical evaluation of the heat shock response to nonablative
      fractional resurfacing.
AB  - Despite the emergence of nonablative fractional resurfacing (NFR) as a new
      therapeutic modality for skin photoaging, little is known about the molecular
      events that underlie the heat shock response to different treatment parameters.
      Human subjects are treated with a scanned 1550-nm fractional laser at pulse
      energies spanning 6 to 40 mJ and a 140-MUm spot size. The heat shock response is
      assessed immunohistochemically immediately through 7 days posttreatment. At the
      immediately posttreatment time point, we observe subepidermal clefting in most
      sections. The basal epidermis and dermal zones of sparing are both found to
      express HSP47, but not HSP72. By day 1, expression of HSP72 is detected
      throughout the epidermis, while that of HSP47 remains restricted to the basal
      layer. Both proteins are detected surrounding the dermal portion of the
      microscopic treatment zone (MTZ). This pattern of expression persists through day
      7 post-NFR, although neither protein is found within the MTZ. Immediately
      posttreatment, the mean collagen denaturation zone width is 50 MUm at 6 mJ,
      increasing to 202 MUm at 40 mJ. The zone of cell death exceeds the denaturation
      zone by 19 to 55% over this pulse energy range. The two zones converge by day 7
      posttreatment.

PMID- 21198216
TI  - Interaction dynamics of spatially separated cavitation bubbles in water.
AB  - We present a high-speed photographic analysis of the interaction of cavitation
      bubbles generated in two spatially separated regions by femtosecond laser-induced
      optical breakdown in water. Depending on the relative energies of the femtosecond
      laser pulses and their spatial separation, different kinds of interactions, such
      as a flattening and deformation of the bubbles, asymmetric water flows, and jet
      formation were observed. The results presented have a strong impact on
      understanding and optimizing the cutting effect of modern femtosecond lasers with
      high repetition rates (>1 MHz).

PMID- 21198218
TI  - Factor structure of a Korean-language version of the Stages of Change Readiness
      and Treatment Eagerness Scale (SOCRATES) in a clinical sample of clients with
      alcohol dependence.
AB  - The Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) is an
      instrument used to measure the level of motivation in regards to changing
      drinking and other addictive behaviors. While some initial factor analysis
      studies on the SOCRATES described a three-factor orthogonal structure of the
      scale, some other studies found a two-factor correlated structure. Therefore, the
      primary objective of the present study was to test the validity of the Korean
      language version of the instrument using a Korean population. The study examined
      the factor structure of the Korean version of the SOCRATES with clinical samples
      consisting of 219 inpatients and 271 outpatients with alcohol dependency. An
      exploratory factor analysis with an alpha factoring method revealed a three
      factor correlated structure (i.e., Taking Steps, Recognition, and Ambivalence).
      The factorial structure of the SOCRATES Korean version corresponded almost
      exactly to that of its original French version as well as the German version.
      Moreover, confirmatory factor analyses showed that a three-factor correlated
      structure provided the best fit for the data.

PMID- 21198219
TI  - Alcohol-involved sexual risk behavior among heavy drinkers living with HIV/AIDS:
      negative affect, self-efficacy, and sexual craving.
AB  - Evidence of the effects of negative affect (NA) and sexual craving on unprotected
      sexual activity remains scant. We hypothesized that NA and sexual craving modify
      the same day association between low self-efficacy to use condoms and unprotected
      anal or vaginal sex, and the same-day association between alcohol use during the
      3 hours prior to sexual activity and unprotected sex. We used an electronic daily
      diary, drawing on a sample of 125 men and women recruited from an agency serving
      economically disadvantaged persons living with HIV/AIDS. Casual or steady partner
      type designation and perceived partner HIV serostatus were also examined.
      Findings support the hypothesized moderating effects of high NA and sexual
      craving on the association between low self-efficacy and unprotected sex, and the
      association between alcohol use and unprotected sex. Implications are discussed.

PMID- 21198220
TI  - Help-seeking for alcohol-related problems in college students: correlates and
      preferred resources.
AB  - Despite the development of a variety of efficacious alcohol intervention
      approaches for college students, few student drinkers seek help. The present
      study assessed students' history of help-seeking for alcohol problems, as well as
      their estimates of how likely they would be to use various help-seeking
      resources, should they wish to change their drinking. Participants were 197
      college students who reported recent heavy drinking (46% male, 68.5% White, 27.4%
      African-American). Participants completed measures related to their drinking and
      their use (both past use and likelihood of future use) of 14 different alcohol
      help-seeking options. Repeated-measures analyses of variance revealed that
      students preferred informal help-seeking (e.g., talking to friends and family)
      over formal (e.g., talking with a counselor or medical provider) and anonymous
      resources (e.g., internet- or computer-based programs). Higher self-ideal
      discrepancy, greater depressive symptoms, and more alcohol-related consequences
      were positively associated with actual past help-seeking. Alcohol-related
      problems and normative discrepancy were negatively associated with hypothetical
      likelihood of utilizing all three help-seeking resources. These results suggest
      that heavy drinking college students prefer low-threshold intervention options
      including peer, family, computerized, and brief motivational interventions. Only
      36 participants (18.3% of the sample) reported that they had utilized any of the
      help-seeking options queried, suggesting that campus prevention efforts should
      include both promoting low-threshold interventions and attempting to increase the
      salience of alcohol-related risk and the potential utility of changing drinking
      patterns.

PMID- 21198221
TI  - Comparison of participatively set and assigned goals in the reduction of alcohol
      use.
AB  - The effects of setting goals on goal commitment, self-efficacy for goal
      achievement, and goal achievement in the context of an alcohol use intervention
      were examined using an experimental design in which participants were randomized
      to participatively set goals, assigned goals, and no goal conditions. One hundred
      and twenty-six heavy-drinking college students received a single cognitive
      behavioral assessment/intervention session and completed measures of goal
      commitment, self-efficacy for goal achievement, and alcohol use. Results were
      consistent with, and expanded upon, previous research by demonstrating that
      having a goal for limiting alcohol consumption was predictive of lower quantity
      and frequency of alcohol use relative to not having a goal. Participation in goal
      setting yielded greater goal commitment and self-efficacy for goal achievement
      than assigned goals, but did not result in significantly greater reductions in
      alcohol use relative to assigned goals. Goal commitment and self-efficacy
      explained unique variance in the prediction of alcohol use at follow-up. Findings
      support the importance of goal setting in alcohol interventions and suggest areas
      for further research.

PMID- 21198222
TI  - Improving the effectiveness of computer-delivered personalized drinking feedback
      interventions for college students.
AB  - This study evaluated methods of enhancing college students' retention of
      information provided to them in a computer-delivered personalized drinking
      feedback intervention and whether enhanced retention reduced alcohol consumption
      during the two-week period following the intervention. Participants were 98
      college students who reported at least one heavy drinking episode in the past two
      weeks. After participating in an online, personalized drinking feedback
      intervention, students were randomly assigned to one of three experimental
      conditions: 1) typical, in which they were simply sent home, 2) reading, in which
      they were asked to spend the next 20 minutes re-reading the feedback, and 3)
      recall, in which they were asked to spend the next 20 minutes writing down as
      much of the information from the feedback as they could remember. Two weeks
      following the intervention, participants completed a recall test and provided
      information on their alcohol use during the previous two weeks. Results indicated
      that participants in the reading and recall conditions retained more of the
      feedback information than did participants in the typical condition. In addition,
      participants in the reading and recall conditions reported reduced alcohol
      consumption in the two-week period following the intervention, compared to those
      in the typical condition. Information retention partially mediated the effects of
      the reading and recall conditions on drinking outcomes.

PMID- 21198223
TI  - Measuring mindfulness and examining its relationship with alcohol use and
      negative consequences.
AB  - Mindfulness has been proposed as a useful adjunct to alcohol abuse treatment.
      However, very little research has examined the basic relationship between alcohol
      use and mindfulness. Inconsistency in definition and measurement of mindfulness
      across studies makes such research difficult to interpret and conduct. Therefore,
      the current research sought to validate an emerging mindfulness measure, the Five
      Facet Mindfulness Questionnaire (FFMQ), and examine its relationship with alcohol
      use and alcohol-related negative consequences among a sample of 316 college-aged
      adults. The purported factor structure of the FFMQ was examined using
      confirmatory factor analysis. Structural equation modeling was used to examine
      relations among mindfulness, alcohol use, and alcohol-related negative
      consequences. Consistent with past research, results supported the five-factor
      structure of the FFMQ. Structural equation modeling analyses revealed that two
      awareness-based factors of mindfulness were negatively related to alcohol use.
      After controlling for alcohol use, one acceptance-based factor (nonjudging of
      thoughts and feelings) was negatively related to alcohol-related consequences,
      and one awareness-based factor was positively related to consequences (all ps <
      .05). Effect sizes were small-medium. The results reported here inform the
      burgeoning development of mindfulness-based addiction treatment and provide
      additional psychometric validation of the FFMQ.

PMID- 21198225
TI  - Drinking behaviors in social situations account for alcohol-related problems
      among socially anxious individuals.
AB  - Individuals with elevated social anxiety appear particularly vulnerable to
      experiencing alcohol-related problems. However, research has thus far failed to
      identify factors that seem to account for this relationship. The present study
      utilized a measure designed to assess alcohol-related behaviors related to social
      situations previously identified as anxiety-provoking among those with elevated
      social anxiety. The Drinking to Cope with Social Anxiety Scale (DCSAS) assessed
      alcohol-related behaviors in 24 social situations and was comprised of two
      subscales: Drinking to Cope in Social Situations and Avoidance of Social
      Situations if Alcohol was Unavailable. Both DCSAS scales demonstrated adequate
      internal consistency and were significantly, positively related to number of
      alcohol-related problems. Individuals with clinically meaningful social anxiety
      (n = 60) achieved higher scores on both DCSAS subscales compared to those with
      lower social anxiety (n = 60). Importantly, the DCSAS scales mediated the
      relationship between social anxiety group classification and alcohol-related
      problems. Results highlight the importance of contextual factors in assessing
      alcohol-related behaviors among high-risk populations.

PMID- 21198224
TI  - Computerized versus motivational interviewing alcohol interventions: impact on
      discrepancy, motivation, and drinking.
AB  - The authors conducted two randomized clinical trials with ethnically diverse
      samples of college student drinkers in order to determine (a) the relative
      efficacy of two popular computerized interventions versus a more comprehensive
      motivational interview approach (BASICS) and (b) the mechanisms of change
      associated with these interventions. In Study 1, heavy drinking participants
      recruited from a student health center (N = 74, 59% women, 23% African American)
      were randomly assigned to receive BASICS or the Alcohol 101 CD-ROM program.
      BASICS was associated with greater post-session motivation to change and self
      ideal and normative discrepancy relative to Alcohol 101, but there were no group
      differences in the primary drinking outcomes at 1-month follow-up. Pre to post
      session increases in motivation predicted lower follow-up drinking across both
      conditions. In Study 2, heavy drinking freshman recruited from a core university
      course (N = 133, 50% women, 30% African American) were randomly assigned to
      BASICS, a web-based feedback program (e-CHUG), or assessment-only. BASICS was
      associated with greater post-session self-ideal discrepancy than e-CHUG, but
      there were no differences in motivation or normative discrepancy. There was a
      significant treatment effect on typical weekly and heavy drinking, with
      participants in BASICS reporting significantly lower follow-up drinking relative
      to assessment only participants. In Study 2, change in the motivation or
      discrepancy did not predict drinking outcomes. Across both studies, African
      American students assigned to BASICS reported medium effect size reductions in
      drinking whereas African American students assigned to Alcohol 101, e-CHUG, or
      assessment did not reduce their drinking.

PMID- 21198226
TI  - Media as social influence: racial differences in the effects of peers and media
      on adolescent alcohol cognitions and consumption.
AB  - Racial differences in the effects of peer and media influence on adolescents'
      alcohol cognitions and consumption were examined in a large-scale panel study.
      With regard to peer influence, results from cross-lagged panel analyses indicated
      that the relation between perceived peer drinking and own drinking was
      significant for both Black and White adolescents, but it was stronger for the
      White adolescents. With regard to media influence, structural modeling analyses
      indicated that exposure to drinking in movies was associated with more alcohol
      consumption 8 months and 16 months later. These effects were mediated by
      increases in the favorability of the adolescents' drinker prototypes, their
      willingness to drink, and their tendency to affiliate with friends who were
      drinking. Multiple group analyses indicated that, once again, the effects (both
      direct and indirect) were much stronger for White adolescents than for Black
      adolescents. The results suggest media influence works in a similar manner to
      social influence and that Whites may be more susceptible to both types of
      influence.

PMID- 21198227
TI  - Implicit and explicit attitudes predict smoking cessation: moderating effects of
      experienced failure to control smoking and plans to quit.
AB  - The current study tested implicit and explicit attitudes as prospective
      predictors of smoking cessation in a Midwestern community sample of smokers.
      Results showed that the effects of attitudes significantly varied with levels of
      experienced failure to control smoking and plans to quit. Explicit attitudes
      significantly predicted later cessation among those with low (but not high or
      average) levels of experienced failure to control smoking. Conversely, however,
      implicit attitudes significantly predicted later cessation among those with high
      levels of experienced failure to control smoking, but only if they had a plan to
      quit. Because smoking cessation involves both controlled and automatic processes,
      interventions may need to consider attitude change interventions that focus on
      both implicit and explicit attitudes.

PMID- 21198229
TI  - The effect of marriage on young adult heavy drinking and its mediators: results
      from two methods of adjusting for selection into marriage.
AB  - This study tested the effect of marriage on young adult heavy drinking and tested
      whether this effect was mediated by involvement in social activities,
      religiosity, and self-control reasons for limiting drinking. The sample of 508
      young adults was taken from an ongoing longitudinal study of familial alcoholism
      that over-sampled children of alcoholics (Chassin, Rogosch, & Barrera, 1991). In
      order to distinguish role socialization effects of marriage from confounding
      effects of role selection into marriage, analyses used both the analysis of
      covariance (ANCOVA) method and the change score method of adjusting for pre
      marriage levels of heavy drinking and the mediators. Results showed role
      socialization effects of marriage on post-marriage declines in heavy drinking.
      This effect was mediated by involvement in social activities such that marriage
      predicted decreased involvement in social activities, which in turn predicted
      decreased heavy drinking. There were no statistically significant mediated
      effects of religiosity. The mediated effect of self-control reasons for limiting
      drinking was supported by the ANCOVA method only, and further investigation
      suggested that this result was detected erroneously due to violation of an
      assumption of the ANCOVA method that is not shared by the change score method.
      Findings from this study offer an explanation for the maturing out of heavy
      drinking that takes place for some individuals over the course of young
      adulthood. Methodologically, results suggest that the ANCOVA method should be
      employed with caution, and that the change score method is a viable approach to
      confirming results from the ANCOVA method.

PMID- 21198228
TI  - Coping strategy use following computerized cognitive-behavioral therapy for
      substance use disorders.
AB  - Coping strategies are emerging as a predictor of treatment outcome for substance
      users and may be particularly important among computerized and self-change
      approaches. We used data from a randomized clinical trial of a computer-based
      version of cognitive-behavioral therapy (CBT4CBT) to: (1) examine the association
      between observer ratings of coping skills and self-reported coping strategies;
      (2) evaluate whether participants assigned to the CBT4CBT program reported
      greater use of coping strategies compared with those not exposed to the program;
      and (3) examine the differential effect of coping strategies by treatment group
      on drug-related outcomes. Individuals (N = 77) seeking treatment for substance
      dependence at a community-based outpatient substance abuse treatment facility
      were recruited and randomized to receive treatment-as-usual (TAU), or TAU plus
      CBT4CBT, with the Coping Strategies Scale administered at baseline and
      posttreatment. Self-reported coping strategy use was strongly correlated with
      observer ratings on a role-play assessment of coping skills. Although no
      significant group differences were found across time for coping strategy use,
      results suggested that as coping strategy use increased, drug use decreased, and
      this relationship was stronger for participants who received CBT4CBT.

PMID- 21198230
TI  - Drug use during pregnancy: validating the Drug Abuse Screening Test against
      physiological measures.
AB  - This study examined the ability of the Drug Abuse Screening Test (DAST-10) to
      identify prenatal drug use using hair and urine samples as criterion variables.
      In addition, this study was the first to use "best practices," such as anonymity,
      ACASI technology, and a written screener, to facilitate disclosure in this
      vulnerable population. 300 low-income, post-partum women (90.3% African-American)
      were recruited from their hospital rooms after giving birth. Participation
      involved (a) completing a computerized assessment battery that contained the DAST
      10 and (b) providing urine and hair samples. Twenty-four percent of the sample
      had a positive drug screen. The sensitivity of the DAST-10 was only .47. Nineteen
      percent of the sample had a positive toxicology screen but denied drug use on the
      DAST-10. Findings suggest that brief drug use screeners may have limited utility
      for pregnant women and that efforts to facilitate disclosure via reassurance and
      anonymity are unlikely to be sufficient in this population.

PMID- 21198231
TI  - Lower task persistence in smokers with schizophrenia as compared to non
      psychiatric control smokers.
AB  - One contributing factor to difficulty in quitting smoking may be task
      persistence, which can be viewed as a behavioral manifestation of distress
      tolerance, and describes the act of persisting in a difficult or effortful task.
      Task persistence was assessed in smokers with schizophrenia and schizoaffective
      disorder (SZ/SA; N = 71) and non-psychiatric controls (N = 78) before a quit
      attempt. These data support the hypothesis that smokers with SZ/SA display less
      task persistence than do non-psychiatric controls when persistence is measured
      via mirror tracing and a 2-item persistence measure. Lower persistence may
      partially explain the reduced smoking cessation successes of smokers with SZ/SA
      as compared to the general population. These data also replicate findings
      regarding relationships between histories of ability to quit smoking and task
      persistence and expand them to a new population of smokers. The absence of a
      diagnostic status by length of previous abstinence interaction suggests that the
      contribution of task persistence to smoking cessation is similar for smokers with
      and without schizophrenia. Future studies should evaluate the ability of task
      persistence to predict abstinence from cigarettes prospectively among smokers
      with schizophrenia.

PMID- 21198233
TI  - Case studies within a mixed methods paradigm: toward a resolution of the
      alienation between researcher and practitioner in psychotherapy research.
AB  - This article addresses the long-standing divide between researchers and
      practitioners in the field of psychotherapy, regarding what really works in
      treatment and the extent to which interventions should be governed by outcomes
      generated in a "laboratory atmosphere." This alienation has its roots in a
      positivist paradigm, which is epistemologically incomplete because it fails to
      provide for context-based practical knowledge. In other fields of evaluation
      research, it has been superseded by a mixed methods paradigm, which embraces
      pragmatism and multiplicity. On the basis of this paradigm, we propose and
      illustrate new scientific standards for research on the evaluation of
      psychotherapeutic treatments. These include the requirement that projects should
      comprise several parallel studies that involve randomized controlled trials,
      qualitative examinations of the implementation of treatment programs, and
      systematic case studies. The uniqueness of this article is that it contributes a
      guideline for involving a set of complementary publications, including a review
      that offers an overall synthesis of the findings from different methodological
      approaches.

PMID- 21198234
TI  - The role of transference work, the therapeutic alliance, and their interaction in
      reducing interpersonal problems among psychotherapy patients with Cluster C
      personality disorders.
AB  - The aim of the present study was to examine whether transference work, the
      therapeutic alliance, and their interaction predicted a reduction in
      interpersonal problems at treatment termination. Forty-nine patients with Cluster
      C personality disorders from a randomized controlled trial investigating the
      effectiveness of short-term dynamic psychotherapy and cognitive therapy were
      included. Transference work was measured with the Inventory of Therapeutic
      Strategies (Gaston & Ring, 1992), while the therapeutic alliance was measured
      with the Helping Alliance Questionnaire (Luborsky, Crits-Christoph, Alexander,
      Margolis & Cohen, 1983). Less emphasis on transference work predicted overall
      reduced interpersonal problems, whereas the effects of the therapeutic alliance
      did not reach statistical significance. An interaction effect was also
      demonstrated, indicating that greater emphasis on transference work performed on
      patients with lower therapeutic alliance ratings was associated with a smaller
      reduction in interpersonal problems at termination. However, the results also
      indicate that a low dose of transference work may be beneficial in reducing
      interpersonal problems.

PMID- 21198235
TI  - Client attachment to therapist: Relation to client personality and
      symptomatology, and their contributions to the therapeutic alliance.
AB  - This study examined the relation of client attachment to the therapist to diverse
      facets of the therapeutic alliance, client personality, and psychopathological
      symptoms, as well as the relative importance of therapeutic attachments,
      personality, and symptomatology in predicting the alliance. Eighty clients in
      ongoing therapy completed measures of client attachment to therapist (CATS),
      personality (6FPQ), psychopathological symptoms (BSI), and therapeutic alliance
      (WAI-Short, CALPAS, HAQ). Secure and Avoidant-Fearful attachment to the therapist
      correlated positively and negatively, respectively, with total and subscale
      alliance scores. Preoccupied-Merger therapeutic attachment was unrelated to the
      alliance. Exploratory analyses suggested however that the relationship between
      Preoccupied-Merger attachment and the alliance was moderated by the extent to
      which clients were distressed. Clients' therapeutic attachments were unrelated to
      basic personality dimensions. Preoccupied-Merger attachment to the therapist
      correlated significantly with several symptom dimensions. Clients' therapeutic
      attachments emerged as superior and more consistent predictors, relative to
      client personality and symptomatology, of the therapeutic alliance.

PMID- 21198236
TI  - Client experience of psychodynamic psychotherapy for bulimia nervosa: an
      interview study.
AB  - We examined 14 bulimic clients' experiences of individual psychodynamic
      psychotherapy through semistructured interviews, which were analyzed using
      qualitative methods. The results showed that the psychodynamic approach was a
      challenge to most of the clients. Yet, most clients profited from therapy both
      symptomatically and with regard to interpersonal relations and affect regulation.
      There were, however, marked differences in the clients' experiences. One subgroup
      rather quickly felt that the therapy met their needs, another initially felt
      challenged by the approach and the therapeutic attitude but ultimately succeeded
      in using this particular kind of therapy. A third group remained predominantly
      critical of their therapies. The clinical implications and possible explanations
      of the results are discussed.

PMID- 21198237
TI  - Should I stay or should I go? Personality Assessment Inventory and Rorschach
      indices of early withdrawal from psychotherapy.
AB  - The Personality Assessment Inventory (PAI) and the Rorschach were used to
      investigate differences between patients who withdrew early from university-based
      outpatient psychodynamic psychotherapy and those who continued in treatment. The
      study employs two sets of analyses, one utilizing the complete sample (N = 101)
      and a second comprised of comparison pairs matched on the specific therapist
      delivering treatment (n = 36 for Rorschach; n = 38 for PAI). It was hypothesized
      that early withdrawers would score higher on the PAI Treatment Rejection Scale
      (RXR) and the PAI Treatment Process Index (TPI) than treatment continuers. It was
      also hypothesized that early treatment withdrawers will have better overall
      interpersonal relationships, less need for closeness and intimacy, less available
      psychological resources and more current stimulus demands, and lower levels of
      psychological/cognitive disturbance as measured by the Rorschach. In addition,
      differences between the two groups on PAI treatment and clinical scales and
      subscales were examined. Results indicated that PAI RXR differentiated between
      the two groups (p< .05) in the expected direction. Limited differences between
      withdrawers and continuers were found on the Rorschach and other PAI scales.
      Potential explanations for the findings as well as a discussion of clinical
      applicability are presented.

PMID- 21198238
TI  - Facilitating congruence between religious beliefs and sexual identity with
      mindfulness.
AB  - With the increasing relevance of sexual minority concerns, including the process
      of navigating sexual and religious identities, clinical practice has focused on
      helping sexual minorities address methods of self-expression that are most
      congruent with the client's values. Sexual Identity Therapy (SIT), (Throckmorton
      & Yarhouse, 2006) has been developed to assist individuals who are seeking to
      address potential conflicts between religious and sexual identities by focusing
      on personal congruence. To facilitate this process, the practice of mindfulness
      is applied. As an adaptation from its spiritual origins, mindfulness is used to
      facilitate the treatment of various disorders, such as chronic pain, substance
      abuse, and depression. It has also been the crux of several different third-wave
      cognitive and behavioral therapies that consider the "... context and functions
      of psychological phenomena" (Hayes, 2004, p. 5) for the purpose of helping
      clients to develop "... broad, flexible and effective repertoires" (p. 6). In
      this instance, mindfulness is applied to SIT to assist individuals with same-sex
      attraction to become nonjudgmentally aware of their thoughts and feelings related
      to same-sex attraction such that they are able to experience their attractions in
      an open and honest manner without feeling compelled to either dismiss or augment
      these attractions. Mindful awareness of same-sex attraction facilitates
      congruence because there is less emphasis on changing behaviors, thoughts or
      feelings, but rather, changing the relationship the individual has to their
      experiences of same-sex attraction so that they are experienced as neutral, as
      opposed to aversive.

PMID- 21198239
TI  - Identifying and integrating helpful and harmful religious beliefs into
      psychotherapy.
AB  - The 2 main roles of the psychotherapist involve identifying and understanding the
      client's problems/strengths and treating problems. Suggestions are offered to
      guide addressing or avoiding religious beliefs in both roles. Types of religious
      beliefs that contribute to distress, particularly for youth, are identified and
      treatment options are offered.

PMID- 21198240
TI  - Mestizo spirituality: toward an integrated approach to psychotherapy for
      Latina/OS.
AB  - Development of culturally syntonic models for treatment that are consistent with
      belief systems of ethnically diverse populations is at a beginning stage of
      evolution. This paper is a step toward laying a new conceptual and
      psychotherapeutic approach with Latina/o clients, specifically those of Mexican
      American and Mexican backgrounds. It is argued that a psychospiritual belief
      system is at the base of these populations, and that a culturally consistent
      framework must appropriately address theory, skills, and practice. Mestizo
      spirituality is presented and described, and a review of those forces that have
      impacted this understanding is offered. Key concepts, therapeutic goals, and
      relationship assumptions of the model, two case examples, application, and
      limitations of this framework are provided. Lastly, implications for professional
      practice are given.

PMID- 21198242
TI  - The real relationship inventory: development and psychometric investigation of
      the client form.
AB  - The development and validation of a client version of the Real Relationship
      Inventory (RRI-C) is reported. Using a sample of clients (n = 94) who were
      currently in psychotherapy, a 24-item measure was developed consisting of two
      subscales (Realism and Genuineness) and a total score. This 24-item version and
      other measures used for validation were completed by 93 additional clients.
      Results of the present study offer initial support for the validity and
      reliability of the RRI-C. The RRI-C correlated significantly in theoretically
      expected ways with measures of the client-rated working alliance and therapists'
      congruence, clients' observing ego, and client ratings of client and therapist
      real relationship on an earlier measure of the real relationship (Eugster &
      Wampold, 1996). A nonsignificant relation was found between the RRI-C and a
      measure of social desirability, providing support for discriminant validity. A
      confirmatory factor analysis supported the two theorized factors of the RRI-C.
      The authors discuss the importance of measuring clients' perceptions of the real
      relationship.

PMID- 21198243
TI  - An algorithm for determining use of trauma-focused cognitive-behavioral therapy.
AB  - The shift toward dissemination of evidence-based practices has led to many
      questions about who is appropriate for a particular treatment model, particularly
      with complex clients, in diverse community settings, and when multiple evidence
      based models have overlapping target populations. Few research-based tools exist
      to facilitate these clinical decisions. The research on trauma-focused cognitive
      behavioral therapy (TF-CBT), an evidence-based treatment for children suffering
      from posttraumatic stress reactions, is reviewed to inform development of an
      algorithm to assist clinicians in determining whether a particular client is
      appropriate for TF-CBT. Recommendations are made for future research that will
      facilitate matching TF-CBT and other evidence-based practices to particular child
      clients.

PMID- 21198244
TI  - Therapists' view of therapeutic action in psychoanalytic psychotherapy with young
      adults.
AB  - Studying experienced therapists' implicit theorizing may contribute to our
      understanding of what is helpful and what hinders treatment with particular
      patient populations. In this study, 16 therapists' views of curative factors,
      hindering factors, and outcome were explored in 22 interviews conducted at
      termination of individual psychoanalytic psychotherapy with young adults.
      Grounded theory methodology was used to construct a tentative model of
      therapeutic action based on the therapists' implicit knowledge. The results
      indicated that developing a close, safe and trusting relationship was viewed as
      the core curative factor in interaction with the patient making positive
      experiences outside the therapy setting and the therapist challenging and
      developing the patient's thinking about the self. The therapeutic process was
      experienced as a joint activity resulting in the patient becoming a subject and
      acquiring an increasing capacity to think and process problems. The patient's
      fear about close relationships was seen as hindering treatment and leading to
      core problems remaining. The model is discussed in relation to major theories of
      therapeutic action in the psychoanalytic discourse and previous research focusing
      on young adults' view of curative and hindering factors in psychotherapy.
      Implications for practice and further research are suggested.

PMID- 21198245
TI  - Gestalt therapy and cognitive therapy--contrasts or complementarities?
AB  - The article investigates the relationship between crucial concepts and
      understandings in gestalt therapy and cognitive therapy aiming at discussing if
      and how they can be mutually enriching when considered as complementary parts in
      a more encompassing integrative therapeutic approach. It is argued that gestalt
      therapy, defined as a field-theoretical approach to the study of gestalt
      formation process, can complement the schema-based understanding and practice in
      cognitive therapy. The clinical benefits from a complementary view of the two
      approaches will be a wider scope of awareness toward individual and contextual
      aspects of therapeutic change processes, toward different levels of memory
      involved in these processes, and toward the relationship between basic needs,
      sensation and cognition in therapeutic work. Further, a dialogue between the two
      approaches will pave the way for addressing the connection between fundamental
      awareness work in gestalt therapy and the tendency within cognitive therapy
      toward incorporating mindfulness as a therapeutic tool. In the conclusion of the
      article, additional complementary points between the two approaches are outlined.

PMID- 21198246
TI  - A review of the neurobiological effects of psychotherapy for depression.
AB  - Although randomized, controlled clinical trials have shown that different forms
      of psychotherapy may be efficacious for depression, psychotherapy has not been
      widely reported to have effects upon the neurobiological concomitants of
      depression in similar ways as medication. Neuroendocrinal changes that occur
      during depression (principally hypercortisolaemia) produce structural and
      functional alterations to the prefrontal cortex, hippocampus, and amygdala, plus
      the connectivity between these regions of the brain. This article reviews the
      evidence to date regarding the neurobiological effects of psychotherapy for
      depression and suggests a hypothetical pathway linking the nurturing effects of
      the therapist-patient "bond" and restoration of neuroendocrinal "balance." This
      pathway may provide a neurobiological causal link between psychotherapy and
      alleviation of depression in the same way as that which exists for
      pharmacological treatments, and argues for a model of depression that includes
      both biological and psychological effects of psychotherapy when considering
      treatment choice and application.

PMID- 21198247
TI  - Effect of client feedback on couple psychotherapy outcomes.
AB  - Using outcome data to monitor the progress of treatment and the therapeutic
      alliance, also known as "client feedback" or "patient-focused research," has
      yielded impressive results in individual psychotherapy. Client feedback has
      demonstrated reductions in premature terminations and improved psychotherapy
      outcomes. However, little research has been conducted using this paradigm with
      couples receiving therapy. The purpose of this study was to investigate whether
      the effectiveness of client feedback would extend to couple therapy. Results from
      a randomized couple clinical trial conducted in a naturalistic setting indicated
      that couples in a client feedback condition demonstrated statistically
      significantly more improvement compared with couples receiving treatment as usual
      and that improvement occurred more rapidly. Also, 4 times as many couples in the
      feedback condition reported clinically significant change by the end of
      treatment.

PMID- 21198248
TI  - Working alliance as a mediator of client attachment dimensions and psychotherapy
      outcome.
AB  - Studies that employ multidimensional attachment measures to explore the impact of
      attachment style on psychotherapy process and outcome are virtually absent in the
      literature. Further, the role of the working (therapeutic) alliance as a mediator
      of the influence of attachment on treatment outcome has not been formally
      investigated. In order to address these gaps in the research, archival data from
      66 psychotherapy clients treated at a university graduate program training clinic
      were used to examine the influence of three adult attachment dimensions (Comfort
      with Closeness, Comfort Depending on Others, and Rejection Anxiety) on the
      therapeutic alliance and outcome, as well as to assess whether the alliance
      mediates the relationship between attachment and therapy outcome. Both Comfort
      with Closeness and Comfort Depending on Others were significantly related to
      alliance and outcome, whereas Rejection Anxiety was not significantly related to
      either variable. Alliance was a significant partial mediator of the effect of
      Comfort with Closeness on outcome. The results suggest that multidimensional
      measures of attachment capture important influences on alliance and psychotherapy
      and that Comfort with Closeness promotes successful outcome by virtue of its
      influence on alliance.

PMID- 21198249
TI  - Dropout and therapeutic alliance: a meta-analysis of adult individual
      psychotherapy.
AB  - This meta-analytic review of 11 studies examined the relationship between
      psychotherapy dropout and therapeutic alliance in adult individual psychotherapy.
      Results of the meta-analysis demonstrate a moderately strong relationship between
      psychotherapy dropout and therapeutic alliance (d = .55). Findings indicate that
      clients with weaker therapeutic alliance are more likely to drop out of
      psychotherapy. The meta-analysis included a total of 1,301 participants, with an
      average of 118 participants per study, a standard deviation of 115 participants,
      and a range from 20 to 451 participants per study. Exploratory analyses were
      conducted to determine the influence of variables moderating the relationship
      between alliance and dropout. Client educational history, treatment length, and
      treatment setting were found to moderate the relationship between alliance and
      dropout. Studies with a larger percentage of clients who completed high school or
      higher demonstrated weaker relationships between alliance and dropout. Studies
      with lengthier treatments demonstrated stronger relationships between alliance
      and dropout. Inpatient settings demonstrated significantly larger effects than
      both counseling centers and research clinics. No significant differences were
      found between client-rated, therapist-rated, and observer/staff-rated alliance.
      Recommendations for clinicians and researchers are discussed.

PMID- 21198250
TI  - Interruption management in the intensive care unit: Predicting resumption times
      and assessing distributed support.
AB  - Interruptions are frequent in many work domains. Researchers in health care have
      started to study interruptions extensively, but their studies usually do not use
      a theoretically guided approach. Conversely, researchers conducting theoretically
      rich laboratory studies on interruptions have not usually investigated how
      effectively their findings account for humans working in complex systems such as
      intensive care units. In the current study, we use the memory for goals theory
      and prospective memory theory to investigate which properties of an interruption
      influence how long it takes nurses to resume interrupted critical care tasks. We
      collected data with a mobile eye tracker in an intensive care unit and developed
      multiple regression models to predict resumption times. In 55.8% of all
      interruptions there was a finite-and therefore analyzable-resumption lag. For
      these cases, the main regression model explained 30.9% (adjusted R2) of the
      variance. Longer interruptions (beta=.36, p<.001) and changes in physical
      location due to interruptions (beta=.40, p<.001) lengthened the resumption lag.
      We also calculated regression models on subsets of the data to investigate the
      generality of the above findings across different situations. In a further 37.6%
      of all interruptions, nurses used behavioral strategies that greatly diminished
      or eliminated individual prospective memory demands caused by interruptions,
      resulting in no analyzable resumption lag. We introduce a descriptive model that
      accounts for how nurses' behaviors affect the cognitive demand of resuming an
      interrupted task. Finally, we discuss how the disruptive effects of interruptions
      in the intensive care unit could be diminished or prevented.

PMID- 21198251
TI  - When training with a partner is inferior to training alone: the importance of
      dyad type and interaction quality.
AB  - Dyad training, where trainees learn in pairs but ultimately perform individually,
      has been shown to be an effective method for training some skills. The
      effectiveness of this approach, however, may be tied to the type of task to be
      trained and the quality of the interaction in the dyad. We report two studies on
      the effectiveness of dyad training and the role of metacognitive activity for
      learning a software program. In Study 1, participants completed training alone or
      with a partner. Performance was assessed individually immediately after training
      and again after a 1-week nonuse interval. Results of Study 1 suggested that
      learning retention is superior when people are trained individually. Study 2
      examined performance for individuals, task-switching dyads, and interdependent
      dyads. Results also showed that performance for individuals was superior to dyads
      and that the type of dyad collaboration did not affect performance. However,
      partner-prompted metacognitive activity was helpful for interdependent dyads and
      harmful for task-switching dyads, suggesting that the quality of collaboration
      varies by dyad type. Our findings suggest that dyad training may not be effective
      for all types of tasks. Possible boundary conditions for effective dyad training
      are discussed.

PMID- 21198252
TI  - Mental rotation: cross-task training and generalization.
AB  - It is well established that performance on standard mental rotation tasks
      improves with training (Peters et al., 1995), but thus far there is little
      consensus regarding the degree of transfer to other tasks which also involve
      mental rotation. In Experiment 1, we assessed the effect of mental rotation
      training on participants' Mental Rotation Test (MRT) scores. Twenty-eight
      participants were randomly assigned to one of three groups: a "One-Day Training,"
      "Spaced Training," or "No Training" group. Participants who received training
      achieved higher scores on the MRT, an advantage that was still evident after 1
      week. Distribution of training did not affect performance. Experiment 2 assessed
      generalization of mental rotation training to a more complex mental rotation
      task, laparoscopic surgery. Laparoscopic surgical skills were assessed using
      Fundamentals of Laparoscopic Surgery (FLS) tasks. Thirty-four participants were
      randomly assigned to a "Full Mental Rotation Training, MRT and FLS," "MRT and
      FLS," or "FLS-only" group. MRT results from Experiment 1 were replicated and
      mental rotation training was found to elicit higher scores on the MRT. Further,
      mental rotation training was found to generalize to certain laparoscopic surgical
      tasks. Participants who obtained mental rotation training performed significantly
      better on mental-rotation dependent surgical tasks than participants who did not
      receive training. Therefore, surgical training programs can use simple computer
      or paper-based mental rotation training instead of more expensive materials to
      enhance certain aspects of surgical performance of trainees.

PMID- 21198253
TI  - Learning and retention through predictive inference and classification.
AB  - Work in category learning addresses how humans acquire knowledge and, thus,
      should inform classroom practices. In two experiments, we apply and evaluate
      intuitions garnered from laboratory-based research in category learning to
      learning tasks situated in an educational context. In Experiment 1, learning
      through predictive inference and classification were compared for fifth-grade
      students using class-related materials. Making inferences about properties of
      category members and receiving feedback led to the acquisition of both queried
      (i.e., tested) properties and nonqueried properties that were correlated with a
      queried property (e.g., even if not queried, students learned about a species'
      habitat because it correlated with a queried property, like the species' size).
      In contrast, classifying items according to their species and receiving feedback
      led to knowledge of only the property most diagnostic of category membership.
      After multiple-day delay, the fifth-graders who learned through inference
      selectively retained information about the queried properties, and the fifth
      graders who learned through classification retained information about the
      diagnostic property, indicating a role for explicit evaluation in establishing
      memories. Overall, inference learning resulted in fewer errors, better retention,
      and more liking of the categories than did classification learning. Experiment 2
      revealed that querying a property only a few times was enough to manifest the
      full benefits of inference learning in undergraduate students. These results
      suggest that classroom teaching should emphasize reasoning from the category to
      multiple properties rather than from a set of properties to the category.

PMID- 21198254
TI  - Finding needles in haystacks: identity mismatch frequency and facial identity
      verification.
AB  - Accurate person identification is central to all security, police, and judicial
      systems. A commonplace method to achieve this is to compare a photo-ID and the
      face of its purported owner. The critical aspect of this task is to spot cases in
      which these two instances of a face do not match. Studies of person
      identification show that these instances often go undetected when mismatches
      occur regularly in an experiment, but this differs from everyday operations in
      which identity mismatches are rare. The current study therefore examined whether
      infrequent identity mismatches are more likely to go undetected by observers. In
      Experiments 1 and 2, identity mismatches were detected equally under low (2%) and
      high (50%) mismatch prevalence. This pattern persisted when viewing conditions
      were optimized for person identification in Experiment 3, by using a card-sorting
      task in which all face identities could be viewed repeatedly, and also under
      increased task difficulty, by constraining viewing conditions temporally in
      Experiment 4. These results imply that the infrequent occurrence of identity
      mismatches in security settings such as passport control does not impair an
      observer's ability to detect these important events.

PMID- 21198255
TI  - Postidentification feedback affects subsequent eyewitness identification
      performance.
AB  - Eyewitnesses sometimes view more than one lineup during an investigation. We
      investigated the effects of postidentification feedback following one lineup on
      responses to a second lineup. Witnesses (N=621) viewed a mock crime and, later,
      attempted to identify the culprit from an initial (target-absent) lineup and a
      second (target-present or target-absent) lineup. Prior to viewing the second
      lineup, some witnesses received accurate feedback stating that the initial lineup
      did not contain the culprit. A compound-decision, signal detection approach
      allowed the effects of feedback on identification responses to be described in
      terms of differences in discriminability and response bias. For witnesses who
      made an incorrect foil identification from the initial lineup, feedback (vs. no
      feedback) was associated with poorer discriminability on the second test. For
      witnesses who correctly rejected the initial lineup, feedback (vs. no feedback)
      was associated with greater discriminability on the second test. Only witnesses
      who received feedback after an initial correct rejection performed at a level
      comparable with a single-lineup control group, suggesting that an initial
      identification test can impair, but not enhance, performance on a second test
      involving the same culprit. From a theoretical perspective, the results are
      consistent with the idea that the way people use memorial information when making
      memory decisions is flexible. Analyses of preidentification confidence ratings,
      obtained in a follow-up study (N=133), suggested that the effects of feedback on
      identification performance may have operated via differences in witnesses'
      metacognitive beliefs.

PMID- 21198256
TI  - The effects of mechanical transparency on adjustment to a complex visuomotor
      transformation at early and late working age.
AB  - Mechanical tools are transparent in the sense that their input-output relations
      can be derived from their perceptible characteristics. Modern technology creates
      more and more tools that lack mechanical transparency, such as in the control of
      the position of a cursor by means of a computer mouse or some other input device.
      We inquired whether an enhancement of transparency by means of presenting the
      shaft of a virtual sliding lever, which governed the transformation of hand
      position into cursor position, supports performance of aimed cursor movement and
      the acquisition of an internal model of the transformation in both younger and
      older adults. Enhanced transparency resulted in an improvement of visual closed
      loop control in terms of movement time and curvature of cursor paths. The
      movement-time improvement was more pronounced at older working age than at
      younger working age, so that the enhancement of transparency can serve as a means
      to mitigate age-related declines in performance. Benefits for the acquisition of
      an internal model of the transformation and of explicit knowledge were absent.
      Thus, open-loop control in this task did not profit from enhanced mechanical
      transparency. These findings strongly suggest that environmental support of
      transparency of the effects of input devices on controlled systems might be a
      powerful tool to support older users. Enhanced transparency may also improve
      simulator-based training by increasing motivation, even if training benefits do
      not transfer to situations without enhanced transparency.

PMID- 21198257
TI  - Comparison of incidence of intrahepatic and extrahepatic cholangiocarcinoma-
      focus on East and South-Eastern Asia.
AB  - BACKGROUND: The term "cholangiocarcinoma" was originally used only for
      intrahepatic bile duct (adeno)carcinomas, but is now regarded as inclusive of
      intrahepatic, perihilar, and distal extrahepatic tumors of the bile ducts. A rise
      in incidence of intrahepatic cholangiocarcinoma has been recently reported in
      Western countries but comparatively little is known about recent
      cholangiocarcinoma incidence trends in East and South-Eastern Asia. METHODS: We
      compared age-adjusted incidence rates of both intrahepatic and extrahepatic
      cholangiocarcinomas, as well as coding practices, using data from 18 cancer
      registries in Asia and 4 selected registries in Western countries. Intrahepatic
      cholangiocarcinoma incidence rates were calculated after reallocation of cases
      with unknown or unspecified histology among liver cancer cases. RESULTS: Age
      adjusted incidence rates of intrahepatic cholangiocarcinoma varied by more than
      60-fold by region. The highest rates were found in Khon Kaen, Thailand, where 90%
      of liver tumors were cholangiocarcinomas. The next highest rates were found in
      the People's Republic of China, followed by the Republic of Korea. The highest
      age-adjusted incidence rate for extrahepatic cholangiocarcinoma was found in
      Korea. Coding practices for perihilar (Klatskin tumor) or unspecified sites of
      cholangiocarcinoma differed from one cancer registry to the other. The proportion
      of Klatskin tumors among cholangiocarcinomas was less than the one reported in
      clinical settings. CONCLUSION: Developing a consistent and uniform topographical
      classification for acceptable coding practice to all health professionals is
      necessary. In addition, epidemiological research on risk factors according to
      anatomical location (intrahepatic versus extrahepatic) and the macroscopic
      appearance and/or new histological classification of cholangiocarcinoma is also
      needed.

PMID- 21198258
TI  - Educational intervention to improve breast health knowledge among women in
      Jordan.
AB  - BACKGROUND: Breast cancer is the most common cancer among women in Jordan and on
      average 70% of the cases present at advanced stages. The aim of this study was to
      assess the effectiveness of a public educational campaign conducted by the Jordan
      Breast Cancer Program to improve breast health knowledge among Jordanian women
      and to relate their knowledge to breast health practices. METHODS: The campaign
      was conducted in five governorates in Jordan with a total of 105 public group
      lectures about breast cancer focusing on early detection. The total number of
      participants was 2,554 women with a median age of 37 years (range: 15-73 years).
      Median number of women per lecture was 24 (range: 9-38). Before the lectures, the
      women answered a structured questionnaire about their knowledge and practices.
      After the intervention 2,418 of them filled a post-test questionnaire with the
      same content. Correct answers on the 15 knowledge questions yielded a maximum
      score of 15. Determinants of breast health practices were identified using
      multivariable logistic regression analysis. RESULTS: The mean knowledge score
      increased significantly from 10.9 in the pre-test to 13.5 in the post-test
      (p<0.001). The percentage with a minimum of 14 correct answers to the 15
      questions increased from 18 to 63% (p<0.001). Adequate breast health practices
      were generally low but increased significantly with increasing age and attendance
      at a previous lecture on breast cancer. Breast health practices were also higher
      among married women and housewives, and significantly associated with older age
      and greater breast health knowledge (p<0.001). CONCLUSIONS: Group educational
      lectures appeared effective for improving breast health knowledge among Jordanian
      women. However, even with the noticeable level of knowledge at the baseline,
      there were low breast health practices among the study participants. This
      necessitates further in-depth research to explore womens experiences and socio
      cultural barriers to breast health seeking behaviour in Jordan.

PMID- 21198259
TI  - Public knowledge on cancer and its determinants among Saudis in the Riyadh Region
      of Saudi Arabia.
AB  - BACKGROUND: Earlier studies on cancer knowledge/awareness from Saudi Arabia have
      been few and mostly limited to knowledge of and attitude towards breast cancer.
      The objectives of the present cross sectional study were to determine the levels
      of knowledge concerning cancer and to identify associated factors. METHODS: This
      study was carried out among 1,407 Saudis who were either patients or their
      escorts, attending selected hospitals in Riyadh region and aged 15 years or more.
      Required information was obtained by interview using a piloted Arabic
      questionnaire. Associations between different variables and respondents knowledge
      were evaluated by Chi square test. Multiple logistic regression analyses were
      performed to examine the potential impact of the variables. RESULTS: This study
      population consisted of 688 males and 719 females. Approximately two thirds of
      participants (67.6%) had never heard of any cancer warning signals, but 80.7%
      believed some cancers can be cured if detected early, 27.1% believed cancer means
      end of life and 74.2% believed cancer will appear overnight. The majority of the
      respondents (65.1%) received information about cancer from television/radio.
      Although 1,159 had high level knowledge (scored 50.0% and more), only 233
      individuals scored 75.0% and more. Significant differences in the knowledge level
      across age groups, educational levels and marital status were observed. Females
      had higher level knowledge than males. Odds of having high level knowledge about
      cancer was 5.27 times higher among those who had undergone any of the tests
      (breast self examination, mammography, occult blood, Papanicolau smear) compared
      to those who had none of those tests (95% CI: 1.87-14.8). Those who had heard
      about any cancer warning signal were more knowledgeable (OR=1.55; 95% CI: 1.10
      2.19) than those who hadn't. The other most important determinants of knowledge
      level included age, and attending a primary health care centre. CONCLUSIONS: Our
      results suggest that the knowledge of cancer is poor among the public and greater
      attempts should be made to increase public awareness.

PMID- 21198261
TI  - Dietary patterns and risk of ductal carcinoma of the breast: a factor analysis in
      Uruguay.
AB  - Breast cancer (BC) shows very high incidence rates in Uruguayan women. The
      present factor analysis of ductal carcinoma of the breast, the most frequent
      histological type of this malignancy both in Uruguay and in the World, was
      conducted at a prepaid hospital of Montevideo, Uruguay. We identified 111 cases
      with ductal BC and 222 controls with normal mammograms. A factor analysis was
      conducted using 39 food groups, allowing retention of six factors analyzed
      through logistic regression in order to obtain odds ratios (OR) associated with
      ductal BC. The low fat and non-alcoholic beverage patterns were inversely
      associated (OR=0.30 and OR=0.45, respectively) with risk. Conversely, the fatty
      cheese pattern was positively associated (OR=4.17) as well as the fried white
      meat (OR=2.28) and Western patterns (OR 2.13). Ductal BC shared similar dietary
      risk patterns as those identified by studies not discriminating between
      histologic type of breast cancer.

PMID- 21198260
TI  - APEX1 Asp148Glu gene polymorphism is a risk factor for lung cancer in relation to
      smoking in Japanese.
AB  - DNA repair enzymes play an important role in the development of various kinds of
      cancer. We here analyzed associations of XPD Lys751Gln, APEX1 Asp148Glu, XRCC1
      Arg399Gln, and XRCC3 Thr241Met gene polymorphisms in DNA repair pathways in
      relation to the risk of lung cancer using PCR-RFLP. The study involved 104 lung
      cancer patients and 120 non-cancer controls divided into non-smokers and smokers.
      We found a statistically significant interaction between APEX1 Asp148Glu and the
      risk for lung cancer (adjusted OR 2.78, 95% CI 1.58-4.90, p=0.0004), of both
      adenocarcinoma (adjusted OR 2.24, 95%CI 1.18-4.25, p=0.014) and squamous cell
      carcinoma (adjusted OR 4.75, 95%CI 1.79-12.6, p=0.002) types. XRCC1 Arg399Gln
      showed a borderline significant association with adenocarcinoma (adjusted OR
      1.89, 95%CI 1.00-3.57, p=0.051). The combined effect of smoking and presence of
      the APEX1 Asp148Glu demonstrated a significant association with risk of lung
      cancer (adjusted OR 3.61, 95% CI 1.74-7.50, p=0.001). The XPD Lys751Gln and XRCC3
      Thr241Met genotypes displayed no statistically significant risk. Our findings
      suggest that the APEX1 Asp148Glu is associated with increased risk for primary
      lung cancer in Japanese individuals partaking in smoking.

PMID- 21198262
TI  - The G-protein beta3 polymorphism is associated with diffuse type gastric cancer
      in Japanese.
AB  - From epidemiological evidence a high salt diet is a risk factor for gastric
      cancer, independent of Helicobacter pylori infection, and animal studies have
      shown that salt promotes carcinogenesis. The G-protein beta 3(GNB3) C825T
      polymorphism has been linked with hypertension, salt sensitivity and multiple
      diseases. Our aim in this study was to clarify any association of the GNB3 C825T
      polymorphism with gastric cancer risk in Japanese. We examined 161 patients with
      gastric cancer and 183 control subjects. All underwent stomach biopsy by
      endoscopic procedures, and extracted DNA was genotyped using a primer pair
      including the GNB3 C825T polymorphism area by PCR-based restriction fragment
      length polymorphism (PCR-RFLP). Logistic-regression analysis was performed to
      assess the impact of the genetic polymorphism. Overall comparison of genotype
      frequency showed the CT genotype in control patients to be relatively infrequent,
      but no statistically significant differences were found. However, on comparison
      of subtypes of gastric cancer (intestinal and diffuse), a significantly increased
      risk of diffuse type of gastric cancer was foudn for the TT genotype (odds ratio
      compared to CC, 3.1, 95%CI 1.1-8.6, p=0.03). In conclusion, the TT genotype of
      GNB3 was associated with diffuse type of gastric cancer. The mechanism of the
      GNB3 polymorphism interaction with gastric cancer development needs to be
      clarified by future study.

PMID- 21198263
TI  - HER-2 expression correlates with survivin in primary invasive ductal breast
      cancers.
AB  - BACKGROUND: The expression of HER-2 and Survivin is correlated with poor
      prognosis of breast cancer, but a possible interaction of these two proteins
      remains to be established. AIM: The aim of this study is to determine the
      possible relationship between HER-2 and Survivin in primary invasive ductal
      breast cancer. METHODS: Eighty-six patients diagnosed with primary invasive
      ductal breast cancer were enrolled in the study. Cancerous breast tissue biopsies
      were analyzed for the expression levels of HER-2, survivin, ERK1/2, p-ERK1/2,
      AKT, and p-AKT proteins by Western blot. The levels of HER-2 and survivin mRNA
      were also assessed by real-time quantitative reverse transcription--polymerase
      chain reaction (RT-PCR). Finally, the correlation of disease state and protein or
      mRNA expression was analyzed using the bivariate Pearson's correlation method
      (two-tailed). RESULTS: Western blot analysis showed a significant correlation in
      protein levels among HER-2, p-AKT, and survivin in the primary invasive ductal
      breast cancer tissues (all p<0.01). However, the levels of HER-2 protein and
      Survivin mRNA were not correlated (p=0.154). CONCLUSIONS: HER-2 expression
      significantly correlates with Survivin at the protein level in primary invasive
      ductal breast cancer tissues, and the correlated changes might act via p-AKT,
      rather than at the level of transcriptional regulation.

PMID- 21198264
TI  - Prognostic factors for elderly breast cancer patients in University Malaya
      Medical Centre, Malaysia.
AB  - BACKGROUND: Information about elderly breast cancer patients' outcome is limited.
      This study aimed to evaluate the treatment outcomes in women aged 70 and above
      with specific analysis on prognostic clinicopathological features and treatment
      modalities. MATERIALS AND METHODS: This retrospective study examined breast
      cancer patients between 1st January 1994 and 31st December 2004 in UMMC. Survival
      analysis was performed using the Kaplan-Meier method and comparisons between
      groups using the log-rank test. Univariate and multivariate analysis on
      prognostic factors were carried out using the Cox's proportionate hazard model
      for patient demographics, and tumour and treatment factors. RESULTS: One hundred
      and thirty six patients were identified, with a median age at diagnosis of 75
      years. Most had at least one co-morbidity (61.8%). Only 75.0% had a good
      performance status (ECOG 0-1). Mean tumour size was 4.4 cm. Primary tumour stages
      (T stages) 3 and 4 were present in 8.1% and 30.1% of patients respectively, and
      30.9% had stage III and 8.8% had stage IV disease based on overall AJCC staging.
      ER positivity was 58.1%. PR status was positive in 30.1%. Surgery was performed
      in 69.1% of the patients and mastectomy and axillary clearance were the commonest
      surgical procedures (50.7%). Some 79.4% of patients received hormonal therapy,
      30.1% radiotherapy and only 3.6% chemotherapy. Non-standard treatment was given
      to 39.0% of patients due to a variety of reasons. The cumulative 5 years overall,
      relapse free and cause specific survivals were 51.9%, 79.7% and 73.3%
      respectively. Performance status, T3-4 tumour, presence of metastasis, tumour
      grade and ER status were independent prognostic factors for overall survival. For
      cause specific survival they were T4 tumour, presence of metastasis and ER
      status. CONCLUSION: The 5 years overall survival rate was 51.9% and 41.8% of
      deaths were non-breast cancer related deaths. Low survival rate was related to
      low life expectancy in this population. Locally advanced disease, metastatic
      disease and high ER negative rates play a major role in the survival of elderly
      breast cancer patients in Malaysia.

PMID- 21198265
TI  - Body mass index and its change in adulthood and breast cancer risk in China.
AB  - OBJECTIVE: To investigate the association between the risk of breast cancer and
      body mass index (BMI) and its change in adulthood. METHODS: A population-based
      case-control study was conducted in China from 2008 to 2009. The study sample
      included 643 cases with pathologically-confirmed breast cancer and 590 controls.
      Information on adult height and weight at diagnosis, at five years before
      diagnosis, and at age 21 years was collected by face-to-face interview using a
      structured questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs)
      were obtained using unconditional logistic regression analyses. RESULTS: There
      was an increased risk of breast cancer associated with overweight or obesity in
      adulthood in Chinese women. Compared with the women who never had overweight or
      obesity in their adulthood, the adjusted ORs of breast cancer were 1.99 (1.42
      2.79) for a BMI >=25.0 at age 21 and just before diagnosis. This rose to 3.04
      (1.18-7.86) if, in addition, BMI >=25.0 was also present five years before
      diagnosis. CONCLUSION: Weight gain throughout adulthood is associated with an
      increased risk of breast cancer in Chinese women.

PMID- 21198266
TI  - Increased risk of breast cancer in multiparous and lactating women attending a
      breast care clinic in Pakistan: a paradigm shift?
AB  - AIMS AND OBJECTIVES: A changing paradigm shift with multiparity (MP) and breast
      feeding (BF) has been reported in recent years in breast cancer (BC). Our aim was
      to observe associations of parity, BF and other risk factors with BC among a
      local population attending a breast care clinic. MATERIALS AND METHODS: A total
      of 1,039 women (mean age 39 +/- 15 years) attended for screening or presented
      with palpable breast lumps at KIRAN, Pakistan. The majority were in middle and
      low socioeconomic strata. As per American Cancer Society (ACS) guidelines 2003,
      mammography and ultrasound were performed, along with fine needle aspiration
      cytology (FNAC) in 195 women with Breast Imaging Reporting and Data Set (BIRADS)
      IV/V, high risk patients with BIRADS III on mammography and with suspicious
      ultrasound findings. RESULTS: The study population was stratified into two
      groups; one with BC on FNAC in 181 women (17%) and other including 858 healthy
      women after screening for cancer. The BC group had relative predominance of MP
      (86% p<0.001), BF (85% p<0.001), family history FH (8% p=0.106) and post
      menopause PM (49% p<0.001) as compared to the healthy population. Estimated
      relative risk (RR) of BC in women with MP, BF, F/H and PM was 3.12 (95% CI=2.05
      4.73; p<0.001), 2.47 (95%CI=1.69-3.61; p<0.001), 1.45 (95%CI=0.93-2.41; p=1.06)
      and 2.33 (95%CI=1.70-3.02; p<0.001) respectively. Higher incidence of BC was
      observed between 30-40 years 23% (p<0.001) and between 40-50 years 38% (p<0.001).
      CONCLUSION: MP, BF and PM have significant associations with BC in the studied
      Pakistani women and this possible paradigm shift now needs to be evaluated for
      confounding factors.

PMID- 21198267
TI  - A retrospective study of primary brain tumors in children under 14 years of age
      at PIMS, Islamabad.
AB  - The aim of present study was to determine the relative frequency of primary brain
      tumors among children under 14 years of age in Pakistan. A retrospective review
      of pediatric primary brain tumors, encountered over 13 years (January 1998
      through July 2010) at the Neurosurgical Unit of the Pakistan Institute of Medical
      Sciences (PIMS), Islamabad, Pakistan, was made covering 231 cases, 142 (61.5%)
      males and 89 (38.5%) females, with a male to female ratio of 1.69:1. The cases
      were divided into 5 age groups each covering three years of life (0-2, 3-5, 6-8,9
      11 and 12-14 years), with the greatest number in age group 3 i.e. 6-8 years (32%)
      and the least number of patients in age groups 1 and 5 (10.3% each). The 231
      malignancies were categorized by site into two groups, supratentorial (83 cases;
      35.9%) and infratentorial (148 cases; 64.1%). The morphological distribution was
      medulloblastoma (33.3%), astrocytoma (24.7%), mixed gliomas (14.7%),
      craniopharyngioma (11.7%), ependymoma (8.7%), PNET (6.1%) and pineal tumor
      (0.9%). Since only a single institution was studied, cautious interpretation is
      needed. Ideally, a population-based approach would be adopted to determine the
      cancer burden due to pediatric malignancies of the brain in this population and
      for their morphological categorization in Pakistan.

PMID- 21198268
TI  - Prevalence and incidence of anemia in Thai patients with gynecologic cancer.
AB  - This prospective, single institute, 6-month observational survey aimed to
      evaluate the prevalence, incidence, frequency, treatment of anemia, and trigger
      hemoglobin (Hb) level for initiating transfusion in patients with gynecologic
      malignancy. One hundred and eighty-six consecutive patients with gynecologic
      malignancy were analyzed between June and December 2009. Hb level data were
      collected for up to six data points or 6 months of scheduled visits. Tumor type,
      disease status, cancer treatment and anemia treatment as well as trigger Hb level
      for starting treatment were evaluated. The mean age of patients was 51 years.
      Prevalence of anemia at enrollment was 66.1% (123/186), with 36 of 186 patients
      (19.4%) having moderate to severe anemia (Hb < 10.0 g/dl). The highest prevalence
      was found among patients with endometrial cancer (72.2%) and ovarian cancer
      (72%), newly-diagnosed/receiving treatment (70.9%) and those receiving
      radiotherapy (75%). The incidence of anemia was 85.7% (54/63). Ovarian cancer had
      the highest association (87%). For disease status and cancer treatment, the
      incidence was highest in patients with persistent/recurrent disease (95.2%) and
      those who received radiotherapy (100%). One hundred and seventy-seven of 186
      patients (95.2%) were ever anemic during the survey. Anemia was frequently
      reported in patients with all tumor types (93-100%), persistent/recurrent disease
      (98.3%) and those who received radiotherapy (100%) and 80.8% of patients who were
      ever anemic received treatment (oral iron, 42.9%; transfusion, 37.3%; and
      erythropoietic agent, 0.6%). In conclusion, the mean Hb trigger level for
      initiating transfusion as treatment of anemia was 8.6g/dL. The prevalence,
      incidence, and frequency of anemia are very high among patients with gynecologic
      malignancy; especially those with ovarian cancer, persistent/recurrent disease,
      and those receiving treatment.

PMID- 21198269
TI  - Estimation of cancer incidence in Japan with an age-period-cohort model.
AB  - Cancer has been the primary cause of death in Japan for many years and accurate
      cancer incidence data are necessary in order to make plans for cancer control.
      Although population-based cancer registries are the best answer, regrettably
      there are still many regions with low accuracy registries. In an alternative
      estimation, cancer incidences have been analyzed by age-period-cohort (APC)
      models, allowing future prediction of cancer incidences in 2004. Considering the
      unexpectedly rapid aging of the Japanese population after this figure was
      reported, it would be worthwhile to examine more recent data. In this study, we
      therefore projected major cancer incidences based on the earlier results leaving
      estimated values for the age and cohort effects. Relating to the period effect,
      the most adequate scenario was selected from 12 projection methods. Furthermore,
      incidences when registration rates varied between 70 and 100% were calculated. As
      a result, different trends from reported incidences were observed for liver
      cancer in males, and trends of registration rates differed by sites. Until stable
      accurate registration data become available, it is difficult to judge whether
      predicted increase is real or only looks so because the registration rate is not
      100%. However, it is clearly necessary to continuously observe variation in
      cancer incidences.

PMID- 21198270
TI  - Antitumoral activity of allicin in murine lymphoma L5178Y.
AB  - Epidemiological studies link increased garlic (Allium sativum) consumption with a
      reduced incidence of cancer in various human populations. Experimental
      carcinogenesis studies in animal models and in cell culture systems indicate that
      several allium-derived compounds exhibit inhibitory effects and that the
      underlying mechanisms may involve apoptosis. To provide a better understanding of
      the effects of allium derivatives regarding prevention of cancer, we examined
      antitumoral activity of allicin, a major component of garlic, in L5178Y lymphoma
      bearing mice. For in vitro studies, we utilized cell proliferation and apoptosis
      in the same tumor cell line. We found that allicin inhibited the growth of tumor
      cells at doses two fold superior to that in normal splenocytes. Allicin also
      induced apoptosis, and this was associated with an increase in caspase3 activity.

PMID- 21198271
TI  - Cardiospermum halicacabum inhibits cyclophosphamide induced immunosupression and
      oxidative stress in mice and also regulates iNOS and COX-2 gene expression in LPS
      stimulated macrophages.
AB  - The effect of a methanolic extract of Cardiospermum halicacabum L was studied
      against cyclophosphamide (CTX)-induced toxicity in mice. Administration of CTX
      (25 mg/kg b.wt, i.p.) for 10 days produced significant myelosuppression as
      evidenced by a decreased WBC count and bone marrow cellularity. Co-treatment with
      Cardiospermum significantly increased the total WBC count, bone marrow
      cellularity and alpha-esterase positive cells, and the relative organ weights of
      spleen as well as thymus compared to the CTX alone treated group. Cardiospermum
      further reduced the enhanced levels of ALP, GPT, LPO, and proinflammatory
      cytokine TNF-alpha, and also significantly increased the glutathione (GSH) level
      in CTX treated animals. The lowered levels of other cytokines like IFN-gamma, IL
      2, GM-CSF, after CTX treatment were also found to be increased by extract
      administration. Histopathological analysis of small intestine also suggested
      reduction of CTX-induced intestinal damage. Moreover the extract down-regulated
      the inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) mRNA
      expression in LPS stimulated macrophages. These studies indicate that C.
      halicacabum could reduce cyclophosphamide induced oxidative stress and
      immunosupression through enhancing the antioxidant status and immunomodulation by
      stem cell proliferation.

PMID- 21198272
TI  - An alternative approach to study the changes in the cancer pattern of women in
      India (1988-2005).
AB  - BACKGROUND: The changes in the cancer pattern are often studied with the help of
      changes in the rank of leading sites, changes in the Age Adjusted Rates of the
      sites over the time or with the help of time trends. However, these methods do
      not quantify the changes in relation to overall changes that occurred in the
      total cancer cases over the period of time. An alternative approach was therefore
      used to assess the changes in cancer pattern in relation to overall changes in
      time and also an attempt was made to identify the most emerging new cancers in
      India. METHODS: The cancer incidence data of various sites for women, over the
      periods 1988-90 and 2003-05 in India, for five urban registries namely Bangalore,
      Bhopal, Chennai, Delhi and Mumbai, functioning under the network of National
      Cancer Registry Programme (ICMR), formed the sources of data for the present
      analysis. The changes in incidence cases by various cancer sites for women were
      assessed by calculating the differences in incidence cases over the two period of
      time. Based on the contribution of each site to total change, the ten most
      leading sites were identified separately for each registry. The relative changes
      in the sites with time were taken to identify the most emerging new cancer cases
      over the period of time. RESULTS: The pooled cancer cases for women among five
      urban registries increased from 29447 cases in 1988-90 to 48472 cases in 2003-05
      registering an increased of about 63.3%. The lowest percentage of increase was
      observed in the registry of Chennai (41.5%) and the maximum in Bhopal (102.0%).
      Based on the pooled figures, the breast cancer contributed to the maximum %
      change (38%), followed by ovarian (8.0%), gallbladder (5.1%), corpus uteri (4.9%)
      and cervix uteri (4.1%). Based on the pooled data and relative changes, the
      emerging new cancers were corpus uteri (187%), gallbladder (162.1%) and lung
      cancer (136.1%). The % change by sites and the emerging new cancers varied
      between the registries.

PMID- 21198273
TI  - Association of the 8473T>C cyclooxygenase-2 (COX-2) gene polymorphism with lung
      cancer risk in Asians.
AB  - OBJECTIVE: To evaluate the impact of the COX-2 gene 8473T>C polymorphism on lung
      cancer risk in Asians, we conducted a comprehensive meta-analysis. METHODS: A
      literature search was performed using PubMed and other databases before June
      2010. We pooled studies according to the variants of 8473T>C and performed
      separate analyses according to ethnicity, histological type and smoking status,
      with attention to study quality and publication bias. RESULTS: A total of five
      case-control studies including 2,450 cases and 4,302 controls were available.
      Overall, individuals with the C allele had a reduced lung cancer risk compared
      with the TT genotype on global analysis (odds ratio [OR] =0.89, 95% confidence
      interval [CI] =0.81 to 0.97, P=0.01, I2 for heterogeneity =0%). Significant
      associations were also observed in subgroups of Asian populations (OR=0.84, 95%
      CI=0.72 to 0.98) when stratified by ethnicity, as well as for small cell lung
      cancer (OR=0.54, 95% CI=0.31 to 0.95) stratified by pathological type.
      CONCLUSIONS: Our results suggest the COX-2 gene is a factor for suffering from
      lung cancer, especially of small cell type among Asians.

PMID- 21198274
TI  - Elevated renin levels in patients with liver cirrhosis and hepatocellular
      carcinoma.
AB  - Liver fibrosis is the common consequence of chronic liver injury of any etiology,
      disrupting the normal architecture,and causing hepatocellular dysfunction and
      portal hypertension. Since the renin-angiotensin system (RAS) may be involved in
      chronic liver diseases, in the present study we assayed renin levels using ELISA
      in groups of Egyptian patients with liver cirrhosis (N=32) and hepatocellular
      carcinoma (HCC) (N=67), for comparison with twenty five healthy controls. The
      results showed significant differences between the control and liver cirrhosis
      patients (P<0.001) and also the controls and HCC patients (P<0.001), without
      significant variation between the patient groups. Furthermore, in HCC patients,
      it was found that the renin levels negatively correlated with serum albumin and
      prothrombin time (P=0.003 for each) and positively with alpha-fetoprotein
      (P=0.04). Thus, it is concluded that renin levels are elevated in patients with
      liver cirrhosis and HCC and suitable medical intervention should be placed for
      management of such alteration. Moreover, further studies are warranted to explore
      its prognostic significance.

PMID- 21198275
TI  - Endometrial cancer in Thai women: clinico-pathological presentation and survival.
AB  - OBJECTIVE: To assess the characteristic features, treatment, survival, and
      prognostic factors of Thai endometrial cancer (EMC) patients. METHODS: Clinico
      pathological data of EMC patients who were treated in the institution from 1992
      to 2008 were collected. Survival rates and prognostic factors were studied.
      RESULTS: The mean age of the 261 patients was 55.4 +/- 9.92 years. The most
      common complaint was abnormal uterine bleeding (87.3%). More than half (75.4%)
      had other medical illnesses or other cancers (10.7%). The majority (78%) had
      early stage disease. Post-operative adjuvant therapy was given in 41.4%; the most
      common was radiation therapy (37.2%). From a median follow-up of 57.5 months
      (range 0.03-212.3 months), progressive disease was encountered in 16 patients.
      Eighteen experienced recurrence (three local, 13 distant metastases and two local
      and distant). Overall, 30 patients died of cancer, while 18 died of other medical
      illnesses. The 5-year progression-free, cancer specific, and overall survivals
      (95% confidence intervals) were 86.5% (82.1-90.8%), 88.0% (83.9-92.2%), and 83.6%
      (78.7-88.4%), respectively. Significant prognostic factors for survival were:
      histology, grade, depth of myometrial invasion, cervical involvement,
      lymphovascular invasion, lymph node status, and Her-2/ neu expression.
      CONCLUSION: Most endometrial cancer patients in Thailand present at early stages
      and experience good survival outcomes.

PMID- 21198276
TI  - Fever/clinical signs and association with neutropenia in solid cancer patients-
      bacterial infection as the main cause.
AB  - INTRODUCTION: Neutropenia remains one of the serious side effects of
      chemotherapeutics drugs making cancer patients face serious risk of infections.
      Fever and clinical signs are considered as important indicators. The objectives
      of this study were to assess fever and clinical signs with neutropenia onset and/
      or severity in solid cancer cases, using culture tests to determine the type of
      bacteria predominating, whether gram positive or gram negative. METHODS: This
      observational retrospective study was conducted on files of all solid cancer
      patients who admitted to a general hospital between 1 January 2003 and 31
      December 2006. All data were categorical and analyzed for association with
      neutropenia. RESULTS: 117 neutropenic patients were studied, 83 (70.9%) of them
      suffering from fever ranging between 38.5-39  degrees C, with hypotension (53;
      27.3%) and headache 51 (26.3%) as the most common clinical signs. Only 34 (29.1%)
      neutropenic patients underwent culture testing and only 14 (41.2%) showed
      positive growth, gram negative types predominating (9; 64.2%), mainly Escherichia
      coli (5; 35.7%), with gram positive only in 5 (35.7%). Significant associations
      were found for fever and clinical signs with neutropenia severity (P<0.05), but
      not neutropenia onset (P>0.05). Logistic regression results showed strong
      significant association between presence of fever (P=0.02, OR=1.3) (95%
      confidence interval (CI)) hypotension and headache (P=0.001, OR=1.148) (95% CI)
      with neutropenia severity. CONCLUSION: Fever and clinical signs specifically
      headache and hypotension are symptoms associated with severe neutropenia in solid
      cancer patients. Both may primarily result from bacterial infection, particularly
      gram negative forms.

PMID- 21198277
TI  - Role of NMP22 Bladder Check Test in early detection of bladder cancer with
      recurrence.
AB  - AIM: To assess clinical utility of NMP22 Bladder Check Test and to compare it
      with voided urine cytology and cystoscopy in early detection of Bladder Cancer.
      MATERIAL AND METHODS: A total of 115 patients of follow up cases of bladder
      cancer were enrolled in this study. Urine samples were assayed for the presence
      of NMP22 using NMP22 Bladder Check Test and cytology was performed by a
      cytopathologist. The diagnosis, determined from the cystoscopic findings and
      biopsy findings of the suspicious lesion was considered as the gold standard. For
      positive biopsies, the results of the NMP22 Test and cytology were also
      correlated with tumour grade and stage. RESULTS: Mean age of the patients was
      57.2 years for males and 55.3 years for females. A total of 59 cases of
      transitional cell carcinomas (TCCs) were diagnosed among which NMP22 test was
      positive in 48 cases and cytology in 26 cases. The sensitivity and specificities
      of NMP22 Test in recurrent bladder cases was 81.3% and 92% which was
      significantly greater than that of cytology 44% and 96.1% respectively. In non
      invasive lesions of TCC, NMP22 Test and cytology was positive in 71.8% and 42.8%
      of cases respectively. In muscle-invasive lesions, NMP22 Test was positive in
      82.2% and 44.4% cases were positive for cytology. The sensitivity of the NMP22
      test was 81.3%, which was significantly greater than that of cytology at 44%.
      CONCLUSION: The NMP22 Bladder Check is a new point of care diagnostic test for
      urinary bladder cancer. The results of our study have shown that the NMP22 can be
      used as a substitute for urine cytology as we achieved high sensitivity and
      specificity with recurrent bladder cases.

PMID- 21198278
TI  - Childhood cancer burden in part of eastern India--Population Based Cancer
      Registry data for Kolkata (1997-2004).
AB  - The increasing magnitude of childhood cancer has become a threatening problem in
      developing countries like India. Data from the Population Based Cancer Registry
      (PBCR) of Chittaranjan National Cancer Institute (CNCI), Kolkata during 1997 to
      2004 were here analyzed. CNCI receives patients from West Bengal as well as other
      neighboring states and countries. Childhood cancer was found to account for 2.21%
      of all cancers registered in this period. Crude and age adjusted rates were
      higher among boys than girls, with leukemia as the commonest (36.8%) followed by
      lymphomas (14.8%) and soft tissue tumors (8.0%). Chemotherapy was the major
      modality of treatment given, followed by radiotherapy and surgery. The study
      provides useful information on the prevalence and management protocols of
      childhood cancer in this part of eastern India.

PMID- 21198280
TI  - Self management pilot study on women with breast cancer: lessons learnt in
      Malaysia.
AB  - OBJECTIVE: With increasing survival rates, breast cancer is now considered a
      chronic condition necessitating innovative care to meet the long-term needs of
      survivors. This paper presents the findings of a pilot study on self-management
      for women diagnosed with breast cancer and their implications for Asian health
      care providers. METHODS: A pre-test/ post-test pilot study was conducted to gain
      preliminary insights into program feasibility and barriers to participation, and
      to provide justification for a larger trial. RESULTS: The study found the 4 week
      self-management program feasible and acceptable, with a favourable trend in
      quality of life. The recruitment barriers ranged from competing medical
      appointments, uncollaborative health providers, linguistic barriers and social
      household concerns. Supporting facilitators identified were family, health
      professionals and fellow participants ("buddies"). Lessons from the study are
      discussed with regard to Asian health providers. CONCLUSION: There is preliminary
      evidence that self management is a workable and potentially useful model even in
      an Asians entrenched-hierarchical medical model of care. The initial challenge
      was breaking down barriers in acceptancee of a collaborative stance. A clinical
      trial is now warranted to gather more evidence.

PMID- 21198279
TI  - Outcome of cervical cancer in Iranian patients according to tumor histology,
      stage of disease and therapy.
AB  - BACKGROUND: Cancer of cervix, the second most common cancer of women overall, is
      a leading cause of cancer death in developing countries. The purpose of this
      study was to measure outcome of treated cervical cancer cases in Yazd since 2002
      to 2009, according to pathology, stage of disease, lymph node involvement and
      therapy. MATERIALS AND METHODS: 100 cases were enrolled and survival was
      determined through phone calls to generate 3 and 5- year-survival rates,
      evaluated by long-rank test with SPSS software. RESULTS: Mean age of the patients
      was 53.6 years, and 3 -year survival was 75.9 %( mean of 59.4 months). In first
      months, survival was the same in both pathology types, but because of the higher
      stages of squamous cell carcinomas in comparison with adenocarcinomas, their
      overall rate was lower. Stage IIB and IIIB survival rates were 90.9% and 30.8%,
      respectively, and rates with and without lymph node involvement were 64.8% and
      80.1%. With para-aortic lymph node involvement, the rate was 85.8% (mean of 65.3
      months). In patients who underwent surgery and chemoradiation, the respective
      figures were 71.6% and 54.9%. Anemic and non-anemic rates were 50% and 78%.
      CONCLUSION: 3-5 year survival of cervical cancer fluctuates in the range of 70 to
      93%. The relationship with lymph node involvement is weak. Survival of women
      receiving chemotherapy was lower than after surgery. Our findings showed an
      importance of diagnosis in primary stages and surgical resection of pelvic and
      para-aortic lymph nodes.

PMID- 21198281
TI  - Inhibition of 1, 2-dimethylhydrazine-induced mucin-depleted foci and O6
      methylguanine DNA adducts in the rat colorectum by boiled garlic powder.
AB  - The scavenging capacity of reactive oxygen species, such as hydroxyl radicals, is
      reported not to decrease in boiled garlic (an odorless garlic preparation). We
      therefore examined the modifying effect of boiled garlic powder (BGP) on 1,2
      dimethylhydrazine-induced mucin-depleted foci (MDF) and aberrant crypt foci
      (ACF), preneoplastic lesions, in the rat colorectum. Male F344 rats (5 weeks old)
      were fed a basal diet, or experimental diets containing 5% or 1% BGP for 5 weeks.
      One week later, all rats were injected s.c. with DMH (40 mg/kg, once weekly for 2
      weeks). At 10 weeks of age, all the rats were sacrificed, and the colorectum was
      evaluated for MDF and ACF. In rats given DMH and the 5% or 1% BGP diets (Groups 2
      and 3), the numbers of MDF decreased significantly in a dose-dependent manner,
      compared with the DMH and basal diet value (Group 1) (p<0.01). The numbers of ACF
      in Group 2, but not Group 3, showed a non-significant tendency to decrease. Next,
      the effects of BGP on the formation of DMH-induced O6-methylguanine (O6-MeG) DNA
      adducts in rats were studied. Male F344 rats (5 weeks old) were fed the basal
      diet, or 10% BGP diet for 5 weeks. All rats were injected i.p. once with 40 mg/kg
      DMH at the end of week 5. The animals were sacrificed 6 hours after DMH injection
      to analyze the O6-MeG DNA adducts in the colorectal mucosa. Dietary
      administration of BGP significantly inhibited the O6-MeG DNA adduct levels in the
      colorectal mucosa, compared with the controls (p<0.01). These results suggested
      that BGP may exert chemopreventive effects against colon carcinogenesis at least
      in the initiation stage.

PMID- 21198282
TI  - Liver cancer screening in Korea: a report on the 2008 National Cancer Screening
      Programme.
AB  - BACKGROUND: The Korean National Cancer Screening Programme (NCSP) for liver
      cancer was initiated in 2003. The objective of this study was to evaluate
      participation in the NCSP and provide essential evidence associated with the
      screening of Korean adults at high risk for liver cancer. METHODS: Liver cancer
      screening was conducted in two stages. During the first, the fraction of the
      population at high risk for liver cancer was identified through detection of the
      hepatitis B virus surface antigen (HBsAg) and hepatitis C virus antibodies (anti
      HCV Ab). During the second stage, this high-risk population was kept under
      surveillance to detect liver cancers as quickly as possible, and screening
      participation rates and recall rates were assessed. We estimated the 95%
      confidence intervals (CIs) for all outcome measures. RESULTS: In the first stage,
      2.57% (95% CI, 2.47-2.67) of Medical Aid Programme (MAP) recipients tested
      positive for HBsAg and 3.70% (95% CI, 3.25-4.15) tested positive for anti-HCV Ab.
      The total target population for liver cancer screening in 2008 included 433,822
      adults over 40 years of age. Of them, 141,381 (32.6%) participated in the NCSP
      for liver cancer. Participation rates were 34.9% for National Health Insurance
      (NHI) recipients and 25.2% for MAP recipients. Among participants, 1,139
      individuals exhibited a positive screening result (recall rate = 0.81%).
      CONCLUSIONS: Our findings demonstrate the current status of liver cancer
      screening in Korea. They provide evidence for implementing an organised liver
      cancer screening programme among high-risk groups.

PMID- 21198283
TI  - Chemomodulatory effects of Aegle marmelos against DMBA-induced skin tumorigenesis
      in Swiss albino mice.
AB  - Aegle marmelos is widely used in Indian Ayurvedic medicine for the treatment of
      diabetes mellitus. In the present study, cancer chemopreventive properties were
      evaluated on 7, 12-dimethylbenz (a) anthracene (DMBA) induced skin
      papillomagenesis in Swiss albino mice. A single topical application of DMBA,
      followed 2 weeks later by repeated application of croton oil till the end of the
      experiment ( i.e. 16 weeks) caused a 100% tumor incidence. In contrast, mice
      treated with the AME (50 mg/kg b. wt./animal/day) in the peri-initiational phase
      (i.e. 7 days before and 7 days after DMBA application; Group IV) and post
      initiational phase (from the day of croton oil treatment till the end of the
      experiment; Group V), exhibited a significant reduction to 70 and 50%
      respectively. The cumulative number of papillomas after 16 weeks was 67 in the
      control group, but 26 and 23 in the animals treated with AME at peri-initiational
      and post-initiational stages, respectively. The tumor burden and tumor yield were
      significantly decreased (Group IV-3.7, 2.6; Group V- 4.6, 2.3) as compared to
      carcinogen treated control group (6.7, 6.7). The present study demonstrates the
      chemopreventive potential of Aegle marmelos fruit extract on DMBA induced skin
      tumorigenesis in mice.

PMID- 21198284
TI  - Predictors of regular gastric cancer screening among Koreans.
AB  - OBJECTIVES: This study analyzed stages of adoption of gastric cancer screening
      and explored relationships with the processes of change, pros, cons, and self
      efficacy in an effort to assess the barriers to and facilitators of regular
      gastric cancer screening. METHODS: The study sample consisted of 650 participants
      who were at least 40 years old, had no history of cancer, and resided in two
      urban areas in Korea. Stages of adoption, processes of changes, pros and cons of
      screening, and self-efficacy were recorded from January 12 to February 16, 2009.
      Data were assessed by analysis of variance and logistic regression. RESULTS: The
      stage of adoption was determined for 650 respondents, of whom 52 were in the
      precontemplation stage (8.0%), 209 in the contemplation stage (32.0%), 52 in the
      action stage (8.0%), and 337 in the maintenance stage (51.8%). Those who
      underwent regular gastric cancer screening were more committed, more willing to
      participate in the healthcare system, perceived fewer cons of screening, reported
      a greater self-efficacy, and perceived gastric cancer risk as moderate.
      CONCLUSIONS: Our findings should be helpful for the development of intervention
      strategies designed to improve recognition of the importance of cancer screening
      and encourage Koreans to undergo regular screening for gastric cancer.

PMID- 21198285
TI  - Flow cytometry results at diagnosis and relapse in childhood acute lymphoblastic
      leukemia.
AB  - INTRODUCTION: Several studies have focused on the immunophenotype of the leukemic
      population at the time of relapse compared to that observed at diagnosis.
      OBJECTIVE: The question of whether differences exist between surface antigens
      levels on blasts at the time of diagnosis and at relapse in cases of acute
      lymphoblastic leukemia (ALL) was addressed. MATERIALS AND METHODS: A total of 25
      All patients were included. Flow cytometry and fluorescein-isothiocynate
      conjugated antibodies were used to determined surface antigens levels. RESULTS:
      The most frequently detected five antigens were I2 (n=21), CD10 (n=17), CD41
      (n=16), CD2 (n=14) and CD7/CD19 (n=13/n=13) at the time of diagnosis and CD41
      (n=21), I2 (n=20), CD10 (n=14), CD19 (n=16) and CD2 (n=12) at the time of
      relapse. There was a significant difference only between CD41 levels at the time
      of diagnosis and at the time of relapse (p=0.041). CONCLUSION: We found changes
      in antigen expressions at the time of relapse in ALL patients. This condition
      ought to be evaluated with reference to prognosis of leukemia.

PMID- 21198286
TI  - Pediatric rhabdomyosarcomas in Tunisia.
AB  - INTRODUCTION: Rhabdomyosarcoma is the most common soft tissue sarcoma in the
      first two decades of life. Since there is a paucity of reports on the pattern of
      its occurrence in Tunisia, we here analysed the epidemiological pattern, clinical
      features, and pathology. DESIGN: We retrospectively studied 30 consecutive cases
      of histologically proven rhabdomyosarcoma in children aged 0-15 years extracted
      from the database of the Cancer Registry of the Center of Tunisia for the period
      1993-2007. RESULTS: Rhabdomyosarcomas represented 53.6% of soft tissue sarcomas
      and 3.8% of all children cancer cases registered during this period. The
      male/female ratio was 2.7 with a mean age at diagnosis of 5.9 years. The
      embryonal subtype was the most frequent (60%) and the two most common sites of
      disease were the head and neck (50%) and genito-urinary tract(23.3%).
      Chemotherapy was used in 90% of patients; 43.3% of patients had radical surgery
      and 26.7% of patients received radiation therapy. CONCLUSION: The epidemiology,
      pathology and clinical features of rhabdomyosarcoma in Tunisian children are
      close to those reported from other countries.

PMID- 21198288
TI  - Factors influencing late consultation among patients with rectal bleeding in
      University Kebangsaan Malaysia Medical Centre.
AB  - BACKGROUND: Patients' delay in the presentation with rectal bleeding had been
      identified as a factor for late diagnosis of colorectal cancer. This study was
      conducted to determine the prevalence of delay in consulting a medical
      practitioner and identifying associated factors. MATERIALS AND METHODS: A cross
      sectional study of 80 patients with rectal bleeding, aged 40 and above, was
      conducted between December 2008 and June 2009 in the endoscopy unit, University
      Kebangsaan Malaysia Medical Centre. The self-administered questionnaire included
      data on sociodemographic, concern of rectal bleeding, whether patients sought
      initial advice, any self treatment prior to medical consultation and patients'
      opinion on causes of their own rectal bleeding. RESULTS: The prevalence of delay
      in the presentation of rectal bleeding was 60%. Patients who were less worried
      (OR 9.6; 95% CI 3.3-27.5), who did not seek anyoneandapos;s advice (OR 11.8; 95%
      CI 3.8-36.8) and took some treatment before seeking medical consultation (OR 5.0;
      95% CI 1.0-24.1) were significantly more likely to delay. Multiple logistic
      regression revealed that less worry of rectal bleeding and not seeking
      anyoneandapos;s advice were important predictors (p<0.05). The majority of
      patients attributed their bleeding to benign causes. CONCLUSION: A high
      proportion of patients with rectal bleeding in the high risk group delayed in
      seeking medical advice. Public education needs to focus on interventions to
      reduce the delay in presenting and diagnosis of colorectal carcinoma.

PMID- 21198287
TI  - Anti-proliferative and apoptotic effects of etoricoxib, a selective COX-2
      inhibitor, on 1,2-dimethylhydrazine dihydrochloride-induced colon carcinogenesis.
AB  - In the present study, we assessed effects of etoricoxib, a non-steroidal anti
      inflammatory drug, on proliferation and apoptosis in 1,2-dimethylhydrazine
      dihydrochloride (DMH) induced colon lesion development. Male SD rats were divided
      into four groups: Group 1 controls receiving the vehicle treatment; Group 2
      administered DMH weekly (30 mg/kg body weight, subcutaneously) alone; Group 3,
      DMH weekly plus etoricoxib (0.64 mg/kg body weight, orally) daily; and Group 4,
      etoricoxib alone. After six weeks of treatment, animals were sacrificed and
      colons were analysed for morphological and histopathological features. Well
      characterized pre-neoplastic aberrations such as multiple plaque lesions,
      hyperplasia and dysplasia were found in the DMH treated group whereas these
      features were reduced with co-administration of etoricoxib. To study apoptosis,
      colonocytes were isolated by metal chelation from colonic sacs and studied by
      fluorescent staining and further confirmed by DNA fragmentation. The DMH treated
      animals had fewer apoptotic nuclei as compared to the controls, but numbers were
      higher with DMH+etoricoxib as well as etoricoxib alone. Expression of
      proliferative cell nuclear antigen (PCNA), assessed by Western blot analysis and
      immunohistochemistry, was found to be elevated by DMH treatment group and again
      reduced by etoricoxib. Results for bromodeoxyuridine incorporation (BrdU) were in
      agreement. It may be concluded that the drug, etoricoxib, has the potential to
      act as an anti-apoptotic and anti- proliferative agent in the colon.

PMID- 21198289
TI  - Histological pattern of primary malignant lung tumours diagnosed in a tertiary
      care hospital: 10 year study.
AB  - Lung cancer is the most frequently diagnosed cancer in the world and is the
      second commonest cancer according to hospital-based data from Kashmir, India. The
      objective of this study was to assess the histopathological pattern of primary
      malignant tumours of lung at a tertiary care hospital among smokers and non
      smokers of both sexes. A total of 783 cases over a 10 years period, were studied,
      including 685 males and 98 females with a mean age at presentation of 57.8 years.
      The most common histological type of tumour in both sexes was squamous cell
      carcinoma (71.3 per cent), followed by small cell carcinoma (20.8 per cent),
      adenocarcinoma (2.6 per cent), bronchioalveolar carcinoma (1.8 per cent) while
      other tumours constituted 3.6 per cent. The two main histological subtypes of
      lung cancer found among smokers was squamous cell carcinoma (72.2 per cent) and
      small cell carcinoma 22.9 per cent. The smoker to non-smoker ratio was 2.14:1.

PMID- 21198290
TI  - Turkish university students' nutritional habits regarding cancer prevention and
      healthy lifestyles.
AB  - AIM: Chronic disorders have been increasing over the past century, and the
      relationship with nutrition has been widely discussed. The present study was
      carried out in order to determine health school students' nutrition styles,
      health lifestyle behavior, and their interactions. METHOD: With a cross-sectional
      design, data from 79 students in the Nursing School were collected via a socio
      demographic data collection form, a nutrition form, and and a Health Promotion
      Life-Style Profile (HPLP) questionnaire. Percentages, McNemar data, Independent
      sample t-test and paired-samples t-test were used in data assessment. RESULTS: No
      significant differences were observed between the number of students with healthy
      nutrition and mean healthy lifestyle scores, pre and post-training. There was
      also no influence of presence of a family member with cancer and weight
      perception. However, there was a significant difference between HPLP scores
      before the training and six months following training (p=0.049) and the mean
      healthy lifestyle scores increased. CONCLUSION: Students with poor nutrition who
      were trained in cancer prevention and healthy diets, demonstrated increase in
      their HPLP, yet this did not make a difference to their healthy nutrition
      behavior.

PMID- 21198291
TI  - Seven-year review of prostate carcinomas diagnosed by TRUS biopsy in a single
      Malaysian institution.
AB  - INTRODUCTION: Analysis of epidemiological as well as survival differences among
      the multiethnic population of Malaysia with prostate cancer is important.
      METHODS: Patients confirmed by transrectal-ultrasonographic-guided-biopsy
      performed from 2002 to 2008 were enrolled and analysed according to ethnicity,
      age, PSA level, Gleason score, stage of disease and survival. RESULTS: Among 83
      patients, there were 38 Malay, 40 Chinese, 3 Indians and 2 others. Median age at
      diagnosis was 69.9 (range: 59-93), 43 patients (51.8%) being diagnosed before the
      age of 70. The median PSA level upon diagnosis was 574 ng/ml (range: 1-8632) and
      the median Gleason score was 7 (range: 2-10). Over half were already in Stage 4
      when diagnosed. The most common site of metastasis was the bone. As a result the
      commonest prescribed treatment was hormonal manipulation. Five patients underwent
      radical prostatectomy and a further thirteen patients had radical radiotherapy
      (stage I: 1 patient, stage II: 7 patients and stage III: 5 patients). Ten
      patients defaulted follow-up. The median disease-specific survival was 21.9
      months (range: 1-53). CONCLUSIONS: Prostatic carcinoma is a disease of the
      elderly and it is frequently diagnosed late in Malaysia. Greater efforts should
      be made to educate Malaysians regarding prostate cancer.

PMID- 21198292
TI  - Chemoprevention by Prunella vulgaris L. extract of non-small cell lung cancer via
      promoting apoptosis and regulating the cell cycle.
AB  - Chemoprevention is one feasible approach to decreasing morbidity and mortality of
      non-small cell lung cancer (NSCLC). The present study aimed to explore the
      mechanisms of chemoprevention of NSCLC by Prunella vulgaris L. (PV) using a PV
      extract of 60% ethanol (P-60). In an A/J mouse model benzo[a]pyrene induction of
      lung tumors was significantly reduced difference by P-60 group. In addition, P-60
      was found to have the ability to regulate cell cycle and induce apoptosis in SPC
      A-1 cells. Therefore, we propose that P-60 has potential as a lung cancer
      chemopreventive agent.

PMID- 21198293
TI  - Enhancement of the cervical cancer screening program in Malaysia: a qualitative
      study.
AB  - INTRODUCTION: Cervical cancer has long been known as a preventable disease. Yet
      it still is a prime women's health issue globally. In Malaysia, the current
      cervical cancer screening program, introduced in the 1960s, has been found to be
      unsuccessful in terms of Pap smear coverage. The aim of this study is to
      determine providers perceptives on the program and the feasibility of practicing
      an organized cervical screening program in Malaysia. METHODS: 11 key informant
      interviews were conducted with policy makers and health care providers from the
      Ministry of Health in Malaysia from October 2009 to May 2010. Interviewees'
      perceptions were explored on current and organized cervical screening program
      based on their expertise and experience. RESULTS: The results highlighted that
      the existing cervical screening program in Malaysia faced flaws at all levels
      that failed to reduce cervical cancer morbidity and mortality. The identified
      weaknesses were poor acceptance by women, lack of commitment by health care
      providers, nature of the program, an improper follow-up system, limited resources
      and other competing needs. Complementarily, all interviewees perceived an
      organized cervical screening program as an alternative approach both feasible and
      acceptable by women and government to practice in Malaysia. CONCLUSION: Better
      screening coverage depends on an effective screening program that incorporates a
      behaviour-based strategy. A new program should be focused in the policy-making
      context to improve screening coverage and to effectively combat cervical cancer.

PMID- 21198294
TI  - Immunohistochemical expression of cytosolic phospholipase A2alpha in non-small
      cell lung carcinoma.
AB  - PURPOSE: Cytosolic phospholipase A2alpha is the main target enzyme for the non
      steroidal anti-inflammatory drugs that have been shown to suppress carcinogenesis
      in both experimental model and epidemiologic studies. METHODS: We examined
      cPLA2alpha expression in normal, premalignant bronchial epithelial cells and
      nonsmall cell lung carcinoma (NSCLC) samples using an immunohistochemical
      staining technique. Included in the current study were 76 NSCLC samples and 52
      bronchial biopsy samples obtained. RESULTS: In the normal bronchial epithelium,
      cPLA2alpha expression was found to be completely negative whereas positive
      cPLA2alpha expression was limited to a few macrophages, inflammatory cells. There
      were relatively more cPLA2alpha positive tumors, as defined by positive staining
      in >10% of tumor cells 24 of 76 tumors (32%). When tumor types were considered,
      there were more cPLA2alpha positive adenocarcinomas compared with squamous cell
      carcinomas (17 of 36 adenocarcinomas (47%) vs. 6 of 34 squamous cell carcinomas
      (18%); P=0.02). Although smokers tended to have more cPLA2alpha positive tumors
      than nonsmokers (23 of 64 tumors in the smokers (36%) vs. 1 of 12 tumors in the
      nonsmokers (8%); P=0.06). CONCLUSION: The results of the current study suggest
      that cPLA2alpha expression may not be a useful intermediate biomarker in
      bronchial chemoprevention trials. Nevertheless, considering the patterns of
      cPLA2alpha expression in tumor cells, cPLA2alpha expression status may be a
      useful parameter when designing treatment strategies for a subset of NSCLC
      patients.

PMID- 21198295
TI  - Characteristics of colorectal mucinous adenocarcinoma in Iran.
AB  - AIMS AND BACKGROUND: Mucinous adenocarcinoma (MA) colorectal cancer accounts for
      10 to 15% of colorectal carcinoma. It is generally thought that patients with MA
      present at a more advanced stage of disease and have a poorer prognosis than
      those with other types of carcinoma. The purpose of the present study was to
      clarify the clinicopathological characteristics of mucinous colorectal carcinoma
      in the Iranian population. METHODS: Between January 2002 and March 2008, Of the
      1283 colorectal cancer patients, 110 patients were considered to have mucinous
      tumors according to pathology report. Patients evaluated on the basis of sex,
      age, location of tumor, stage, differentiation of tumor and family history of
      cancer. Kaplan-Meier curves and log-rank tests were used for survival analysis.
      RESULTS: The median age of these patients at diagnosis was 50.07 years. More than
      50% of patients were younger than aged 50 years. 34.5% of patients had a family
      history of colorectal cancer in their first-degree relatives. Most tumors were
      presented in right colon. 54.3% of MA patients had advanced stage lesions. The
      Kaplan-Meier method indicated that, the 1, 3 and 5 year survival rates are 92.6,
      80.1 and 41.3 percent, respectively. Survival of the patients was related to
      disease stage (P = 0.023). CONCLUSION: Our suggests that genetic factors may be
      play an important role in the development of this disease in our country and
      screening programs, especially genetic screening programs, should be considered
      as a main measure for prevention and control of colorectal cancer in Iran.

PMID- 21198296
TI  - Erythrocyte catalase and carbonic anhydrase activities in lung cancer.
AB  - AIM: To study the relationship between the pathogenesis of lung cancer and
      antioxidant status and acidic media by measuring the activities of erythrocyte
      catalase (CAT) and carbonic anhydrase (CA). METHODS: A total of 26 patients with
      lung cancer and 15 healthy individuals were included in the study. The CAT and CA
      activities of erythrocytes were defined. The catalase (CAT) activity of
      erythrocytes was measured using Aebi's method. Carbonic anhydrase (CA) activity
      was analyzed by CO2 hydration. RESULTS: It was found that erythrocyte CA and CAT
      activities were significantly lower in patients with lung cancer compared to
      controls (p<0.05). Of the 26 patients with lung cancer, seven (26.9%) had
      metastasis, and the CA and CAT levels in patients with metastasis were
      significantly decreased (p=0.0001). CONCLUSIONS: Development of oxidative stress
      due to lung cancer may be related to the balance between prooxidant and
      antioxidant reactions. Catalase may have a preventive effect for malignant lung
      cancers and the gene of the antioxidant enzymes may be one of the anti-oncogenes,
      and inactivation of one of these genes in the process of carcinogenesis may lead
      to tumor development. This may be an explanation for the very low levels of
      antioxidant CAT in patients with lung cancer compared to healthy individuals.
      Carbonic anhydrase (CA) in tumor cells may be an indicator of the acid-base
      balance in lung cancer. Decreased levels of CA in patients with lung cancer may
      provide a convenient media for tumor development, growth and metastasis by
      creating an acidic media.

PMID- 21198297
TI  - Some mineral, trace element and heavy metal concentrations in lung cancer.
AB  - OBJECTIVE: We aimed to determine the relationship between some mineral, trace
      element and heavy metal levels in the patients of lung cancer by measuring serum
      levels of copper (Cu), lead (Pb), zinc (Zn), iron (Fe), cobalt (Co), cadmium
      (Cd), manganese (Mn), magnesium (Mg). METHODS: A total of 50 lung cancer and
      human health (30 lung cancer and 20 healthy human) were included in the study.
      Venous blood samples of each lung cancer were obtained, and serum Cu, Pb, Zn, Fe,
      Cd, Co, Mn, Mg levels were analysed by Atomic Absorption Spectrophotometer
      measurements. RESULTS: Mg value measured in lung cancer group were lower than the
      control group and this was statistically significant (P<0.01). Serum Cu level was
      significantly lower with lung cancer compared to healthy human (P<0.01). Pb level
      was significantly higher than those of controls (P<0.01). The serum Zn level was
      significantly lower in serum of lung cancer group than controls (P<0.01). Serum
      Mn and Co levels were found increased in lung cancer group than controls
      (P<0.01). Cd value was higher in lung cancer but it was not statistically
      significant (p>0.01). The mean concentration of Fe in the serum of lung cancer
      patients was higher than in the controls, but the difference was not significant
      (p>0.01). There was a positive correlation between Cd and Pb level, and between
      Mn and Fe levels in lung cancer. There was a negative correlation between Co and
      Zn levels of healthy humans. There was a negative correlation between Co and Mg
      levels of lung cancer. CONCLUSIONS: Serum Cu, Pb, Zn, Fe, Mg, Co, Mn and Cd might
      play a role in the patients with lung cancers. Zn may protective as potent lung
      cancer. In addition, it is suggested that low levels of zinc can facilitate the
      pathogenesis of lung cancer.

PMID- 21198298
TI  - Role of intraoperative imprint cytology in diagnosis of suspected ovarian
      neoplasms.
AB  - BACKGROUND: The present study was conducted to assess whether cytology can help
      in rapid diagnosis of ovarian neoplasms and thus facilitate individualised
      treatment. METHODS: A prospective investigation was performed on 30 cases of
      suspected ovarian neoplasms. Imprint smears were made intraperatively from fresh
      samples from various representative areas, and stained with Leishman Giemsa for
      air-dried smears, and with hematoxylin and eosin and Papanicolaou for alcohol
      fixed smears. A rapid opinion regarding the benign or malignant nature of the
      lesion and the type of tumour was given. RESULTS: The overall sensitivity was
      96.2%, specificity 75%, positive predictive value 96.3%, and diagnostic accuracy
      of 83.3%. Characteristic cytological patterns were noted in various epithelial
      and germ cell tumours. CONCLUSIONS: Imprint cytology can be used as an adjunct to
      histopathology for rapid and early diagnosis in the operation theatre, thus
      helping better management of patients.

PMID- 21198299
TI  - Incidence and prognostic importance of molecular genetic defects in children with
      acute myeloblastic leukemia.
AB  - INTRODUCTION: Acute myeloblastic leukemia (AML) accounts for 15 to 25 percent of
      childhood acute leukemias. The most common genetic abnormalities seen in
      pediatric AML patients are AML1-ETO, PML-RARalpha and CBFB-MYH11 genes resulting
      in t(8;21), t(15;17) and inv(16). These genetic defects are seen in approximately
      20-25% of AML patients. OBJECTIVE: We investigated in this study, incidence and
      prognostic significance of the AML1-ETO, PML-RARalpha and CBFB-MYH11 genes in
      children with AML. MATERIALS AND METHODS: The authors analyzed 34 children with
      AML using the real time-polymerase chain reaction for AML1-ETO, PML-RARalpha and
      CBFB-MYH11 genes. RESULTS: Of the patients, 8.8% were positive for t(8;21), 8.8%
      for t(15;17) and 3% for inv(16). There were a statistically significant
      differences between 48 month overall survival rates of the patients positive and
      negative for t(8;21), t(15;17) and inv(16). CONCLUSION: It was concluded that
      t(15;17), t(8;21) and inv(16) impact on disease prognosis positively, but
      comprehensive studies with larger patient series are now needed for confirmation.

PMID- 21198300
TI  - Can self vaginal douching for high risk HPV screening replace or assist efficacy
      of cervical cancer screening?
AB  - OBJECTIVE: To study the accuracy of self vaginal douching and collection for HPV
      types 16, 18, 31 and 33 in women visiting Thammasat Hospital for the explicit
      purpose of cervical screening. METHODS: A pelvic examination and Pap smear were
      performed for all women who came for cervical screening. Specimens were also
      collected by self vaginal douching before cervical screening and sent to the cell
      and molecular biology laboratory for analysis of human papillomavirus (HPV) types
      16, 18, 31 and 33 using the polymerase chain reaction (PCR). RESULTS: HPV
      prevalence was 3.6% overall from 250 women in this study. Twenty-four (9.6%)
      women had an abnormal cytology screening result. No cancer was found. Four women
      had a high grade squamous intraepithelial lesion (HSIL) and 14 had a low grade
      squamous intraepithelial lesion (LSIL) from colposcopic biopsy. Self vaginal
      douching for HPV 16, 18, 31 and 33 was used to predict abnormal Pap smear.
      Sensitivity, specificity, positive predictive value (PPV) and negative predictive
      value (NPV) were 12.5%, 97.5%, 33.3% and 91.3%, respectively. CONCLUSION: From
      our analysis of self-vaginal douching for HPV detection using cases from
      Thammasat university hospital, it cannot replace the Pap smear.

PMID- 21198301
TI  - Quality of life and influencing factors in patients with a gynaecologic cancer
      diagnosis at Gazi University, Turkey.
AB  - Negative impacts of gynecologic cancers on women's health are multi-dimensional.
      The aim of this study was to determine the quality of life (QOL) of affected
      patients in comparison with a control group diagnosed with gynecological problems
      other than cancer, and to investigate demographic and socio-cultural factors
      potentially affecting QOL. The study, performed between June-December 2008,
      covered 120 inpatients diagnosed with gynecological cancer at the Gynecologic
      Oncology Department of Gazi University Medical School and 123 educational level
      and age matched outpatients without cancer, of the Department of Obstetrics and
      Gynecology Outpatient Unit. Data were collected through a face to face
      questionnaire form including basic socio-cultural and demographic characteristics
      and a quality of life scale (Short Form-36, SF-36). Data entry and analysis were
      performed with the SPSS v11.5 package program and comparisons were conducted
      according to socio-demographic and disease-related characteristics of
      participants. Averages of total scores and all components of the SF-36 Scale of
      the case group were significantly lower in the cancer group. It is essential to
      ensure multidisciplinary approaches for living areas determined to be affected by
      gynecological cancer and also to make efforts to enhance quality of life;
      therefore, some suggestions were made regarding these issues, peculiarly
      considering early diagnosis of gynecological cancer.

PMID- 21198302
TI  - High tumour stage and margin clearance are still important prognostic factors for
      post-mastectomy locoregional recurrence in Malaysia.
AB  - BACKGROUND: Locoregional recurrence after mastectomy for breast cancer may
      predict distant recurrence and mortality. This study examined the pattern and
      rates of post-mastectomy locoregional recurrence (PMLRR), survival outcome and
      prognostic factors for isolated PMLRR (ILR) in a breast cancer cohort in
      University of Malaya Medical Center (UMMC). METHODS: We studied 522 patients who
      underwent mastectomy between 1998 and 2002 and followed them up until 2008. We
      defined PMLRR as recurrence to the axilla, supraclavicular nodes and or chest
      wall. ILR was defined as PMLRR occurring as an isolated event. Prognostic factors
      for locoregional recurrence were determined using the Cox proportional hazards
      regression model. RESULTS: The overall PMLRR rate was 16.4%. ILR developed in 42
      of 522 patients (8.0%). Within this subgroup, 25 (59.5%) remained disease free
      after treatment while 17 (40.5%) suffered disease progression. Univariate
      analyses identified race, age, size, stage, margin involvement, lymph node
      involvement, grade, lymphovascular invasion and ER status as probable prognostic
      factors for ILR. Cox regression resulted in only stage III disease and margin
      involvement as independent prognostic factors. The hazard of ILR was 2.5 times
      higher when the margins were involved compared to when they were clear (aHRR 2.5;
      95% CI 1.3 to 5.0). Similarly, compared with stage I those with Stage II (aHRR
      2.1; 95%CI 0.6 to 6.8) and stage III (aHRR 4.6; 95%CI 1.4 to 15.9) had worse
      prognosis for ILR. CONCLUSION: Margin involvement and stage III disease were
      identified to be independent prognostic factors for ILR. Close follow-up of high
      risk patients and prompt treatment of locoregional recurrence were recommended.

PMID- 21198303
TI  - Comparison of knowledge and practices of breast self examination (BSE): a pilot
      study in Turkey.
AB  - OBJECTIVES: The aim of this descriptive study was to determine breast self
      examination (BSE) knowledge and practice of middle-aged females. METHODOLOGY: The
      study population comprised over 40 year old women (n=252) and nurses (n=29)
      working in a total of seven family health centers in Bolu, Turkey. Data were
      obtained through face to face interviews from September 2007 to January 2008.
      RESULTS: A highly significant relation was identified between increasing age in
      women and lack of BSE and improper practice of BSE steps (p<0.05), and between a
      higher degree of education and presence of breast cancer in the family and
      knowledge and practice of BSE (p<0.05). On the other hand, it was found that
      93.1% of the nurses involved in the study practiced BSE. CONCLUSIONS: The
      findings from this study revealed that educational programs aimed at increasing
      older women's knowledge level of BSE are required and nurses, as medical
      professionals meeting women in various environments, can play a key role in
      increasing women's awareness about breast health.

PMID- 21198304
TI  - Epidemiological and excision margin status of Basal cell carcinoma--three years
      Armed Forces Institute of Pathology experience in Pakistan.
AB  - OBJECTIVE: The rationale of this study is to analyze the demographic distribution
      and clearance of excision margin in basal cell carcinoma among patients diagnosed
      at AFIP Rawalpindi. MATERIALS AND METHODS: Records of a total of 235 cases
      diagnosed from January 2005 to December 2007 were retrieved from our tumour
      registry. The following variables were recorded for each patient: age, gender,
      site of biopsy, type of biopsy (incisional vs excisional) and status of clearance
      of surgical margins. The data was analyzed using SPSS version 17.0. RESULTS:
      Among the total of 235 cases, 125 (53.2%) were males and 110 (46.8%) were females
      (1.2:1). The ages ranged from 32 to 90 years with mean age of 60.0 + 11.7, with a
      general age-dependent increase. The nose was the most frequent site (28.9%),
      followed by the eye, including the orbit (24.7%), and the cheek (20.4%). Among
      the type of biopsies, 140 (59.6%) were excisional and 95 (40.4%) were incisional.
      With the former, the excision margins were reported as clear in 82 (34.9%) cases
      and involved in 55 (23.4%) cases. CONCLUSION: Basal cell carcinoma (BCC) appears
      to be on the rise in our part of world. Careful clinical assessment, and complete
      excision with the help of frozen sections can avoid recurrence.

PMID- 21198305
TI  - Perceived family support of women with breast cancer and affecting factors in
      Turkey.
AB  - BACKGROUND: The purpose of this study was to examine the percieved family support
      of the women with breast cancer and the affecting factors. METHODS: The subjects
      were breast cancer cases undergoing treatment (n=240). The sample for this study
      was formed by women who accepted participation, were in the facility between the
      dates and hours when the study was applied, and who were selected with a
      nonprobability sampling technique (n=120). RESULTS: Two thirds of the women with
      breast cancer were in the 40-59 age group. The lowest score women with breast
      cancer for perceived family support scale was 0.00 and the highest was 40.0, with
      a mean of 30.1+/-8.85. CONCLUSION: In this study, it was determined that
      perceived family support of Turkish women with breast cancer was reasonable.

PMID- 21198306
TI  - Screening of bloodborne pathogens and antimicrobial susceptibility testing among
      cancer patients.
AB  - AIM: To screen bloodborne pathogens and test for antimicrobial susceptibility
      among patients with different types of cancer. MATERIALS AND METHODS: Fifty
      volunteers undergoing chemotherapy in Madurai, Tamilnadu (14 males and 36
      females) provided blood samples with consent for identification of pathogens by
      streaking on different selective and differential media. The antibiotic
      sensitivity for the entire isolates were tested by the Kirby-Bauer method.
      RESULTS: Pseudomonas aeruginosa was found to be present in more samples than
      Proteus mirabilis, Staphylococcus aureus, and E.coli. Percentage sensitivities of
      blood pathogens to selected antibiotics were found to be: Amikacin 61%,
      Gentamicin 68%, Co-Trimoxole 31%, and Cefepime 42.8%.

PMID- 21198307
TI  - Pattern and implications of therapy abandonment in childhood acute lymphoblastic
      leukemia.
AB  - Abandonment of therapy is cited as an important factor contributory to inferior
      survival outcome in developing nations. In this communication we describe the
      pattern of therapy abandonment and its impact on survival of childhood acute
      lymphoblastic leukemia at a large tertiary care center in Northern India and
      discuss remedial measures.

PMID- 21198308
TI  - Is anorectal assessment really useful?

PMID- 21198309
TI  - Differences in the pressures of canal anal and rectal sensitivity in patients
      with fecal incontinence, chronic constipation and healthy subjects.
AB  - INTRODUCTION: There exists a great variability in the manometric findings between
      patients with anal incontinence (AI) and healthy subjects. The correlation
      between the pressures of the anal canal and the AI is not exact by the wide rank
      of normal values. OBJECTIVES: Prospective study to evaluate differences in the
      pressures of the anal canal and in rectal sensitivity in patients with AI,
      chronic constipation (CC) and healthy subjects. MATERIAL AND METHODS: Ninety four
      patients with AI, 36 patients with CC and 15 healthy subjects were included. The
      following data were obtained: age, sex, resting pressure, anal canal length
      (ACL), squeeze maximum pressure (SMP), squeeze pressure duration (SPD), first
      sensation, urge and maximum tolerated volume (MTV). Statistical study: test of
      Kruskal-Wallis, test of Mann-Whitney, and multinomial logistic regression test.
      RESULTS: There were significant differences in the resting pressure (p < 0.001),
      the ACL (p < 0.001) and the SMP (p < 0.01) in the group of AI with respect to the
      other two groups. The volume for the first sensation was significantly lower in
      the healthy subjects than that in the other two groups (p < 0.05). The urge
      volume and the MVT were smaller in the group with AI with respect to the other
      groups (p < 0.001). In multivariate analysis the age, the resting pressure and
      the volume for the first sensation and urge increase the relative risk for AI.
      CONCLUSIONS: The greater age, the decrease in anal canal resting pressure and the
      alteration of rectal sensation increase the risk for AI.

PMID- 21198310
TI  - Usefulness of manometry to select patients with anal fissure for controlled anal
      dilatation.
AB  - AIM: To evaluate the use of anorectal manometry to select patients for controlled
      anal dilatation. METHODOLOGY: A prospective study was performed using anorectal
      manometry on all patients with chronic anal fissure who did not have a good
      response to conservative treatment. Those with increased anal resting pressure
      were treated with controlled anal dilatation using a two valved anuscope. A
      second anorectal manometry was indicated after controlled anal dilatation.
      RESULTS: 19 patients without anorectal pathology (Healthy Control Group) and 57
      patients with chronic anal fissure were included in this study. Controlled anal
      dilatation was performed on 27 patients, maximum resting pressure 122 +/- 19
      mmHg. In the controlled anal dilatation group the healing rate was 92.5%, mean
      maximum resting pressure post-controlled anal dilatation was 91 +/- 30 mmHg. We
      found one case of transitory anal incontinence (3.7%). None of the patients had
      anal incontinence at 18 months of the follow-up. In the remaining 30 patients non
      selected for controlled anal dilatation (chronic anal fissure control group), a
      proportion of 53.3% recurrences were registered after conservative treatment.
      CONCLUSIONS: Anal healing of chronic anal fissure and a significant decrease in
      maximum resting pressure recorded by manometry confirms the success of this
      procedure. The manometric evaluation of the maximum resting pressure is useful in
      the selection of chronic anal fissure patients for controlled anal dilatation.
      The efficacy of dilatation to treat chronic anal fissure in patients with raised
      anal sphincter pressure was high and complications were rare.

PMID- 21198311
TI  - Clinical impact of high-definition endoscopic ultrasonography (EUS) in a district
      hospital.
AB  - OBJECTIVES: Evaluation of the impact of EUS in clinical practice. METHODS: All
      exploration performed during the first 18 months of implementation of the
      technique were analyzed. Agreement was assessed by radiographic techniques or
      surgical specimens in those cases allowed. RESULTS: 277 exploration were
      performed. There have been only 2 complications and they were related to sedation
      in both cases. The demand increased gradually, reaching 70 scans per 100,000
      inhabitants. Main indications were bile (34.3%) and pancreatic processes. No
      pathology was found in 10% of cases; 29 cases had choledocholithiasis (93%
      confirmed and treated endoscopically). Chronic pancreatitis was diagnosed in 19
      cases (only 15.78% of the cases were diagnosed by computed tomography). 32
      patients with idiopathic acute pancreatitis were evaluated: 20 of them had
      evidence of microlithiasis (80% cholecystectomized and asymptomatic after a mean
      follow-up of 21.5 months), two cases of choledocholithiasis, 1 with chronic
      pancreatitis and 9 cases remained free of filial etiology. We performed 56
      punctures: 39 samples of pancreas in 33 patients (81.1% of the samples were
      diagnostic; adenocarcinoma and serous cystadenoma were the most common
      diagnoses), 13 enlarged nodes and 4 abdominal masses. CONCLUSIONS: EUS is a
      growing demand technique that has low risks and leads to better decision-making
      in a significant number of patients with different diseases. Therefore, its
      inclusion in routine clinical practice must be considered.

PMID- 21198312
TI  - Self-expanding plastic stents for the treatment of post-operative esophago-jejuno
      anastomosis leak. A case series study.
AB  - OBJECTIVE: Self-expandable plastic stents (SEPS) are increasingly being used for
      treatment of postoperative esophageal leak. This complication occurs in 4-27% of
      patients after radical gastrectomy, and has a high mortality rate up to 60%.The
      aim of this study is to evaluate the efficacy of SEPS (Polyflex(r)) for treatment
      of post-operative esophago-jejuno anastomosis leak after radical gastrectomy for
      gastric cancer. MATERIAL AND METHODS: During one year period patients who
      underwent a radical gastrectomy in our hospital for gastric cancer and developed
      a postoperative anastomotic leak were prospectively included in the study after
      signing a consent form, and treated with SEPS placement under endoscopic and
      fluoroscopic control for leak occlusion. RESULTS: Four patients were included (3
      men/1 woman). The mean interval between operation and SEPS placement was 16 days
      (range: 4-34). SEPS deployment was easily performed in all patients with complete
      occlusion of esophageal lumen in three patients. In the fourth patient we needed
      to deploy a second coaxial stent to achieve a complete occlusion of the fistula.
      SEPS migration did not happen in our series. One patient had already developed a
      mediastinitis by the time we placed the SEPS and he died 3 days later. Extraction
      of the SEPS was easily performed 4-8 weeks after deployment. CONCLUSION: We
      achieved a complete healing of the anastomotic fistula after radical gastrectomy
      in 3 out of 4 patients, without major complications related to SEPS. Placement of
      SEPS is an appealing minimally invasive alternative to surgical repair for
      patients with postoperative anastomotic leak.

PMID- 21198313
TI  - Irritable bowel syndrome immune hypothesis. Part two: the role of cytokines.
AB  - OBJECTIVE: To review the available evidence on the role of interleukins in the
      etiopathogenesis of Irritable Bowel Syndrome. METHODS: Bibliographic retrieval on
      PubMed including the MeSH terms "Irritable Bowel Syndrome, "Immune System",
      "Cytokines" and "Interleukins". RESULTS: Sixteen case-control studies and one
      randomised controlled trial were retrieved. The blood appears to have a high
      concentration of pro-inflammatory cytokines (TNF- a , IL-1 a , IL-6, IL-8) and
      lower concentration of IL-10, an anti-inflammatory cytokine, even though the
      findings are disparate and heterogeneous. As many as 33 genes were found, each
      with different expressions, and a diminished expression of cytokines in the colon
      mucosa of patients with IBS, which have not been previously described in any
      other pathology. CONCLUSIONS: In patients with IBS, a clear profile of cytokine
      levels in the blood does not appear to exist, although an imbalance between them
      can be observed. Moreover, there are indications that give reason to believe that
      the different subsets of patients with IBS could present cytokine profiles in
      different blood. On the other hand, in the intestine, high cytokine secretion
      levels are not detected, contrary to what would be expected. Further studies are
      required to substantiate these findings.

PMID- 21198314
TI  - Severe anemia by rectal prolapse.

PMID- 21198315
TI  - Cat scratch colon. A new ethiopathogenic possibility.

PMID- 21198316
TI  - Solid pseudopapillary tumor of the pancreas (SPPT). Still an unsolved enigma.
AB  - Solid pseudo-papillary tumor (SPPT) is a rare cystic tumor of the pancreas (1-3%
      of exocrine tumors of the pancreas) which shows an "enigmatic" behavior on the
      clinical and molecular pattern. A retrospective analysis of the cytological
      studies and resected specimens of pancreatic cystic tumors from May 1996 to
      February 2010 was carried out. Three cases of SPPT were found, which are the
      objective of this study. The diagnosis was established upon occasional finding in
      the abdominal CT, in spite of sizing between 3 and 6 cm of diameter. In the three
      cases the preoperative diagnosis was confirmed by cytology and specific
      immunohistochemical staining. Cases 2 and 3 showed strong immunoreactivity for
      Beta-Catenin and E-Cadherin staining. Radical resection (R0) was carried out in
      the three cases. A young male -21 years of age (case 1)- who had duodenal
      infiltration and two lymph nodes metastases died of hepatic and peritoneal
      recurrence 20 months following surgery. The other two cases are free of disease.
      The current review of the literature reports roughly 800 cases since the first
      report in 1959, and shows the enigmatic character of this tumor regarding the
      cellular origin, molecular pathways, prognostic factors and clinical behavior.

PMID- 21198317
TI  - [Extra-abdominal manifestation of acute pancreatitis: paniculitis mediastinic].

PMID- 21198318
TI  - [Secondary pneumopericardium to pneumatosis intestinalis. An uncommon
      complication of a rare disease].

PMID- 21198319
TI  - Intraductal papillary mucinous neoplasm--the experience of natural history.

PMID- 21198320
TI  - Ectonucleotide pyrophosphatase/phosphodiesterase 1 K173Q polymorphism is
      associated with diabetic nephropathy in the Taiwanese population.
AB  - Diabetic nephropathy is the leading cause of end-stage renal disease in the
      world. The cause of diabetic nephropathy seems to be multifactorial, and about
      one-third of patients with diabetes eventually develop this complication. The
      gene encoding ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is a
      candidate susceptibility gene for obesity and type 2 diabetes. We assessed
      rs1044498 (K173Q) located in the ENPP1 gene for association with diabetes
      nephropathy among 201 diabetic subjects without nephropathy and 215 diabetic
      subjects with nephropathy in the Taiwanese population. The single-nucleotide
      polymorphism (SNP) rs1044S498 in ENPP1 was associated with diabetes nephropathy
      in our study subjects. The AC+CC genotype of the rs1044498 SNP was a risk factor
      for the development of nephropathy in diabetic patients. Further, the AC+CC
      genotype of rs1044498 was a genetic risk factor in obese (defined by waist
      circumference) diabetic patients, but not in nonobese diabetic patients. We
      confirmed the association between the rs1044498 SNP in ENPP1 and diabetic
      nephropathy, especially among obese diabetic patients, in the Taiwanese
      population.

PMID- 21198321
TI  - JAK2 V617F gene mutation in the laboratory work-up of myeloproliferative
      disorders: experience of a major referral center in Lebanon.
AB  - AIMS: JAK2 V617F mutation is gaining more acceptance in laboratory testing as
      part of the differential diagnosis work-up of myeloproliferative disorders (MPD).
      This report is the first of its kind from Lebanon that analyzes the distribution
      of this mutation among a series of referred cases to a major tertiary referral
      center. METHODS: Real-time polymerase chain reaction using JAK2 V617F MutaScreen
      assay (IPSOGEN Cancer Profiler) was performed on 229 patients. RESULTS: JAK2
      V617F mutation was found to be positive in 100% of polycythemia vera cases,
      68.29% of essential thrombocythemia cases, and 55.28% of all MPD cases whereas
      negative in idiopathic erythrocytosis, reactive thrombocytosis, and other non-MPD
      cases such as acute chronic myeloid leukemias. CONCLUSION: Our unique study in
      this sample of Lebanese patients shows extensive similarities of positivity of
      JAK2 V617F as compared with the international literature and for the same
      categories of clinical entities. This will constitute a baseline for future
      clinical studies that would also help determine prognosis of cases based on the
      absence or presence of this mutation.

PMID- 21198322
TI  - The effect of participating in suicide research: does participating in a research
      protocol on suicide and psychiatric symptoms increase suicide ideation and
      attempts?
AB  - The effect of engaging in an intensive research protocol that inquired
      extensively about psychiatric and suicide symptoms and exposed participants to a
      number of images, including suicide-related content was explored. Individuals
      experiencing a major depressive episode were called at 1 and 3 months after the
      initial protocol. Participants were asked about changes in suicide ideation and
      the occurrence of self-harm or suicide attempts following participation.
      Participants reported experiencing reductions in suicide ideation at the first
      follow-up and no changes at the second follow-up. No participant reported having
      engaged in self-harm or having attempted suicide at either follow-up. Results
      suggest that basic science/nontreatment research can be conducted safely with
      suicidal participants and in a manner that does not increase suicide symptoms or
      suicide risk.

PMID- 21198323
TI  - Recent suicidal ideation and suicide attempts in a large-scale survey of the U.S.
      Air Force: prevalences and demographic risk factors.
AB  - One-year prevalences of self-reported noteworthy suicidal ideation and nonfatal
      suicide attempts were assessed in a large sample of U.S. Air Force active duty
      members (N = 52,780). Participants completed the 2006 Community Assessment, which
      was conducted online. Over 3% of male and 5.5% of female participants reported
      having experienced noteworthy suicidal ideation during the previous year, and
      8.7% of those with ideation reported a recent suicide attempt. Demographic
      factors predicting significantly increased risk for suicidal ideation included
      female gender, low rank, and non-Christian religious affiliation; unmarried men
      were also at increased risk. Groups that were at increased risk for nonfatal
      suicide attempts included low-ranking men and Hispanic women. Implications for
      prevention efforts are discussed.

PMID- 21198324
TI  - Association between tryptophan hydroxylase 2 gene polymorphism and completed
      suicide.
AB  - The association between suicide and a single nucleotide polymorphism (rs1386483)
      was examined in the recently identified tryptophan hydroxylase 2 (TPH2) gene.
      Blood samples of 143 suicide victims and 162 age- and sex-matched controls were
      examined. The frequency of the TT genotype in the TPH2 polymorphism was higher in
      suicide victims than in controls (17.5% vs. 8.6%; p = 0.02), particularly in
      those with a history of repeated suicide attempts (53.3% vs. 8.6%; p < 0.0001).
      The examined TPH2 polymorphism was found to be associated with suicide. This
      genetic marker may be particularly important in understanding risk of multiple
      suicide attempts. Further analyses are needed to confirm these results.

PMID- 21198325
TI  - Perceived burdensomeness, familism, and suicidal ideation among Mexican women:
      enhancing understanding of risk and protective factors.
AB  - The interpersonal-psychological theory of suicide and a culturally-relevant
      construct, familism, was used to examine predictors of suicidal ideation among
      Mexican and Mexican American women in the United States. A sense of perceived
      burdensomeness toward others was expected to significantly predict suicidal
      ideation, especially among women who endorsed high levels of familism. Mexican
      and Mexican American outpatient women (N = 73) completed self-report measures and
      an interview measure of suicidal ideation. Main and interactive effects of
      perceived burdensomeness and familism were examined. Perceived burdensomeness,
      but not familism, significantly predicted suicidal ideation. The interaction
      hypothesis was not supported. These findings highlight perceived burdensomeness
      as a risk factor for suicidal behavior in Mexican and Mexican American women.

PMID- 21198326
TI  - "The Great Transformation" and suicide: local and long-lasting effects of 1930
      bank suspensions.
AB  - Depression-era bank suspensions and failures are conceptualized as products of
      the first part of what Polanyi (1994) called "The Great Transformation," which
      involved an imbalanced institutional arrangement in which the economy dominated
      other institutions. Relying on Durkheim (1897/1951) and Merton (1938, 1968), it
      is argued that these banking problems accentuated the type of chronic anomie that
      Durkheim theorized would create normative deregulation and elevated suicide rates
      over the long-term. Results from county-level analyses are supportive as the 1930
      bank suspension rate is positively related to the 2000 suicide rate, controlling
      for contemporary and historical factors. The mediating roles of integration and
      chronic anomie are considered, with the latter measured using data from the
      geocoded General Social Survey.

PMID- 21198327
TI  - Attempted suicide, self-harm, and violent victimization among regular illicit
      drug users.
AB  - Relationships among attempted suicide, nonsuicidal self-harm, and physical
      assault were examined in 400 regular users of heroin and/or psychostimulants.
      Twenty-eight percent had episodes of nonsuicidal self-harm, 32% had attempted
      suicide, and 95% had been violently assaulted. The number of suicide attempts and
      nonsuicidal self-harm incidents were correlated (rho = 0.44). There were also
      significant correlations between the number of assaults and nonsuicidal self-harm
      incidents (rho = 0.17), and suicide attempts (rho = 0.27). The mean age onset for
      non-suicidal self-harm (18.9 yrs) was significantly younger than that of initial
      suicide (22.3 yrs). The age at initial physical assault (16.0yrs) was
      significantly younger than that of nonsuicidal self-harm and initial suicide
      attempt. Screening for all forms of violence appears warranted when determining
      suicide risk for this population.

PMID- 21198328
TI  - Severe pain predicts greater likelihood of subsequent suicide.
AB  - Using data from the 1999 Large Health Survey of Veterans, Veterans Affairs'
      medical records, and the National Death Index (N = 260,254), the association
      between self-reported pain severity and suicide among veterans as examined, after
      accounting for demographic variables and psychiatric diagnoses. A Cox
      proportional hazards regression demonstrated that veterans with severe pain were
      more likely to die by suicide than patients experiencing none, mild, or moderate
      pain (HR: 1.33; 95% CI: 1.15, 1.54), after controlling for demographic and
      psychiatric characteristics. These results indicate that pain evaluations should
      be included in comprehensive suicide assessments and suicide prevention efforts.

PMID- 21198329
TI  - Who are the owners of firearms used in adolescent suicides?
AB  - In this brief report, the source of firearms used in adolescent suicides was
      examined using data from the National Violent Injury Statistics System, the pilot
      to the CDC's National Violent Death Reporting System, a uniform reporting system
      for violent and firearm-related deaths. Data represent the 63 firearm suicides
      among youth (<18 yrs) that occurred in 2001 or 2002 in one of four states (CT,
      ME, UT, WI) or two metropolitan counties (San Francisco, CA; Allegheny County,
      PA). Four-fifths of the suicides took place in the decedents' homes, and--when
      the firearm owner was known--most of the firearms were owned by parents. Findings
      replicate results from previous research and highlight the importance of limiting
      youth access to firearms.

PMID- 21198330
TI  - Rethinking impulsivity in suicide.
AB  - Elevated impulsivity is thought to facilitate the transition from suicidal
      thoughts to suicidal behavior. Therefore, impulsivity should distinguish those
      who have attempted suicide (attempters) from those who have only considered
      suicide (ideators-only). This hypothesis was examined in three large nonclinical
      samples: (1) 2,011 military recruits, (2) 1,296 college students, and (3) 399
      high school students. In sample 1, contrary to traditional models of suicide
      risk, a unidimensional measure of impulsivity failed to distinguish attempters
      from ideators-only. In samples 2 and 3, which were administered a
      multidimensional measure of impulsivity (i.e., the UPPS impulsive behavior scale;
      Whiteside & Lynam, 2001), different impulsivity-related traits characterized
      attempters and ideators-only. Whereas both attempters and ideators-only exhibited
      high urgency (the tendency to act impulsive in the face of negative emotions),
      only attempters exhibited poor premeditation (a diminished ability to think
      through the consequences of one's actions). Neither attempters nor ideators-only
      exhibited high sensation seeking or lack of perseverance. Future research should
      continue to distinguish impulsivity-related traits that predict suicide ideation
      from those that predict suicide attempts, and models of suicide risk should be
      revised accordingly.

PMID- 21198331
TI  - Likelihood of suicidality at varying levels of depression severity: a re-analysis
      of NESARC data.
AB  - Although it is clear that increasing depression severity is associated with more
      risk for suicidality, less is known about at what levels of depression severity
      the risk for different suicide symptoms increases. We used item response theory
      to estimate the likelihood of endorsing suicide symptoms across levels of
      depression severity in an epidemiological data set. Regardless of depression
      severity, suicide attempts were less frequently endorsed than ideation, which was
      less frequently endorsed than feeling like one wanted to die. All suicide
      symptoms were generally less likely to be endorsed than other depression
      symptoms. There was a low probability of suicidality at depression levels that
      likely would not merit a diagnosis of major depression.

PMID- 21198332
TI  - Adolescent help-seeking and the Yellow Ribbon Suicide Prevention Program: an
      evaluation.
AB  - The Yellow Ribbon Suicide Prevention Program has gained national and
      international recognition for its school- and community-based activities. After
      the introduction of Yellow Ribbon to a Denver-area high school, staff and
      adolescents were surveyed to determine if help-seeking behavior had increased.
      Using a pre-post intervention design, staff at an experimental school and
      comparison school were surveyed about their experiences with student help
      seeking. Additionally, 146 students at the experimental high school were
      surveyed. Staff did not report any increase in student help-seeking, and
      students' reports of help-seeking from 11 of 12 different types of helpers did
      not increase; the exception was help-seeking from a crisis hotline, which
      increased from 2.1% to 6.9%. Further research with larger, more inclusive samples
      is needed to determine whether Yellow Ribbon is effective in other locations.

PMID- 21198333
TI  - On-line support and resources for people bereaved through suicide: what is
      available?
AB  - The Internet is a potentially valuable source of information for the bereaved,
      but the current knowledge regarding the type and quality of online material on
      suicide bereavement is very limited. This study was designed to explore the types
      of online information and support available for people bereaved by suicide and
      the quality of such resources. Four popular Internet search engines were searched
      using terms related to suicide bereavement and support. Although a wide range of
      Internet resources exist for people bereaved by suicide, these resources may not
      meet basic quality standards. It is unknown who uses these sites, how such
      material is used, and whether it helps people to cope effectively with grief
      after suicide.

PMID- 21198336
TI  - Human mesenchymal stromal cells preserve their stem features better when cultured
      in the Dulbecco's modified Eagle medium.
AB  - BACKGROUND AIMS: The human mesenchymal stromal cell (hMSC), a type of adult stem
      cell with a fibroblast-like appearance, has the potential to differentiate along
      the mesenchymal lineage and also along other cell lineages. These abilities make
      hMSC a promising candidate for use in regenerative medicine. As the hMSC
      represents a very rare population in vivo, in vitro expansion is necessary for
      any clinical use. hMSC characterization is commonly carried out through the
      expression of specific markers and by the capability of differentiating toward at
      least adipo-, osteo- and chondrocytic lineages. Commitment processes also result
      in significant changes in the ultrastructure in order to acquire new functional
      abilities; however, few studies have dealt with the ultrastructural
      characteristics of hMSC according to the time of incubation and type of media.
      METHODS: The immunophenotype, functional characteristics and ultrastructural
      features of bone marrow (BM) hMSC cultured in two different media were
      investigated. The media chosen were Iscove's modified Dulbecco's medium (IMDM)
      and the Dulbecco's modified Eagle medium (DMEM). The latter has been recommended
      recently by two international transplantation and cytotherapy societies, the
      International Society of Cellular Therapy (ISCT) and European Group for Blood and
      Bone Marrow Transplantation (EBMT), for hMSC expansion for clinical applications.
      RESULTS AND CONCLUSIONS: The present results indicate that culture conditions
      greatly influence hMSC ultrastructural features, proliferation, growth and
      differentiation. In particular, our findings demonstrate that DMEM preserves the
      hMSC stem features better. Furthermore, the results obtained in IMDM suggest that
      a small size does not always correlate with conditions of cell immaturity and a
      greater proliferative potential.

PMID- 21198335
TI  - Use of animal protein-free products for passaging adherent human adipose-derived
      stromal/stem cells.
AB  - Adherent adipose-derived stromal/stem cells (ASC) have been used in pre-clinical
      regenerative medical studies applied to a broad range of tissues with an ultimate
      goal of translating these findings to clinical safety and efficacy testing;
      however, many protocols passage the cells using porcine-derived trypsin. We have
      compared porcine trypsin with animal protein-free products from recombinant
      bacteria (TrypLE Express; Invitrogene) and corn (TrypZean; Sigma) based on cell
      yield, viability and immunophenotype. ASC harvested with each trypsin product
      were comparable.

PMID- 21198337
TI  - Systemic absorption of oral vancomycin in patients with Clostridium difficile
      infection.
AB  - Oral vancomycin is utilized in the treatment of severe Clostridium difficile
      infection (CDI). We prospectively measured serum vancomycin concentrations (SVC)
      in patients treated with oral vancomycin. The SVC was measured by immunoassay
      prior to, and at least 3 days after, the administration of oral vancomycin 125 mg
      every 6 h. Patients treated with intravenous vancomycin were excluded. Fifty
      seven patients with a mean age of 74 y (+/- 18) were enrolled. There was no
      detectable SVC in 56 patients (98%); 1 patient had a transient SVC of 6.7 MUg/ml
      that was not detectable on subsequent testing. The severity of the CDI and/or
      renal failure did not have an effect on SVC. Orally administered vancomycin at
      125 mg 4 times daily was not absorbed from the gastrointestinal tract.

PMID- 21198338
TI  - Pediatric therapists' perspectives on occupation-based practice.
AB  - AIMS: The aim of this study was to describe the perspectives on occupation-based
      practice of 22 pediatric occupational therapists in a medical facility in the
      Midwestern United States. METHODS: The study used a grounded theory approach to
      analyze the individual, semi-structured interviews of 22 pediatric occupational
      therapists. Transcripts were initially coded using EthnographTM 5.0 software and
      analysis continued using constant comparison techniques and memo writing to
      produce emergent themes of meaning. FINDINGS: The doing of occupation-based
      practice was based in personal identity and influenced by professional education.
      Occupation-based practice was more satisfying and rewarding for therapists, and
      they found it more effective and individualized. Patients and families were
      perceived by therapists to find occupation-based practice more motivating,
      understandable, valuable, and easily generalized to everyday life. However,
      occupation-based practice was seen as more difficult in a medical-based facility
      because pragmatic factors and contextual forces exerted strong influences.
      CONCLUSIONS: Therapists used specific creative strategies to negotiate between
      competing paradigms to maximize occupation-based practice within constraints.

PMID- 21198339
TI  - Treatment of severe drooling with botulinum toxin in amyotrophic lateral
      sclerosis and Parkinson's disease: efficacy and possible mechanisms.
AB  - OBJECTIVE: Drooling in neurodegenerative diseases is associated with social
      impediment. Previous treatments of drooling have little effect or are effective
      but with severe side effects. Therefore, there is a need to test new methods such
      as the use of botulinum toxin type A (BTX-A). MATERIAL AND METHODS: This open,
      prospective study deals with treatment of drooling in 12 patients with
      amyotrophic lateral sclerosis and three with Parkinson's disease. Injections of
      BTX-A (Botox) were given into the parotid (25-40 units) and submandibular (15-30
      units) glands with ultrasonographic guidance. After BTX-A treatment, the patients
      were followed for 2 months with evaluations every second week by means of self
      assessed rating scales for drooling intensity, discomfort and treatment effect,
      and determination of unstimulated whole saliva (UWS) flow rate, and inorganic and
      organic UWS composition. The treatment was repeated up to four times, but seven
      patients dropped out shortly after the first treatment due to marked worsening of
      their disease-related condition. RESULTS: Drooling and flow were reduced (P <
      0.05) 2 weeks after treatment, without side-effects. The maximal reductions
      during the observation period were 40% for drooling and 30% for flow. There was a
      systematic variation in flow during the observation period, with an initial
      decrease and then an increase followed by a second decrease. Amylase activity and
      total protein concentration generally increased with decreasing flow (P <= 0.03).
      CONCLUSION: Inhibition of acetylcholine release from postganglionic
      parasympathetic nerve endings by injection of BTX-A into salivary glands seemed
      useful for secondary sialorrhoea, although cyclic variations in flow may occur,
      possibly due to transitory sprouting and regeneration.

PMID- 21198340
TI  - The totally implantable middle ear device 'Esteem' for rehabilitation of severe
      sensorineural hearing loss.
AB  - CONCLUSION: The Esteem((r)) device proved to offer beneficial results in subjects
      suffering from high frequency, severe bilateral sensorineural hearing loss (SNHL)
      and may be considered as an alternative procedure to conventional hearing aids
      (HAs) or electroacoustic stimulation (EAS) systems. OBJECTIVES: Since the
      Esteem((r)) totally implantable device has been shown to offer positive results
      among patients with moderate SNHL, this middle ear implant has also been
      suggested for subjects with a worse degree of hearing loss in order to predict
      its extended application, also in the nearly cochlear implantation range.
      METHODS: Esteem((r)) implantation was carried out in 21 subjects with a mild (n =
      3), moderate (MHL, n = 9) or severe (SHL, n = 9) degree of SNHL. The two latter
      groups, i.e. MHL and SHL, were compared in terms of preoperative versus
      postoperative pure tone and speech reception thresholds (SRTs). Similarly, they
      were also compared for the outcome from quality of life (QoL) questionnaires,
      such as the general Glasgow Benefit Inventory (GBI) and COSI. RESULTS: In the
      whole sample, mean hearing threshold levels improved from 70 to 48 dB; in the MHL
      group the mean hearing threshold level improved from 64 to 42 dB; in the SHL
      group the mean hearing threshold level improved from 82 to 58 dB. GBI and COSI
      scores were only slightly better in the MHL group than in the SHL group.

PMID- 21198341
TI  - Dendritic and spinal pathology in the acoustic cortex in Alzheimer's disease:
      morphological estimation in Golgi technique and electron microscopy.
AB  - CONCLUSIONS: The morphological and morphometric estimation of the dendrites and
      the dendritic spines in the acoustic cortex in Alzheimer's disease revealed
      substantial alterations of the dendritic arborization and marked loss of the
      dendritic spines, which may be related to communication impairment even in early
      cases of Alzheimer's disease. OBJECTIVES: Alzheimer's disease is characterized by
      progressive loss of memory, impairment of judgment, and decline in communication
      and speech eloquence. In the present study we attempted to describe the
      morphological and morphometric alterations of the dendrites and the dendritic
      spines in the acoustic cortex in early cases of Alzheimer's disease, in order to
      approach the communication impairment of patients suffering from Alzheimer's
      disease from a neuropathological point of view. METHODS: We studied the acoustic
      cortex in 22 cases of Alzheimer's disease by Golgi technique and electron
      microscopy. RESULTS: The morphological and morphometric estimation of the
      acoustic cortex revealed loss of Cajal-Retzius cells in layer I, as well as an
      impressive abbreviation of the dendritic fields associated with loss of dendritic
      spines in all the layers of the cortex. Numerous distorted, dystrophic, and
      degenerated dendritic spines were also seen, which were intermixed with a
      considerable number of giant spines. The dendritic and spinal alterations were
      closely associated with mitochondrial alterations.

PMID- 21198342
TI  - Rhinoscleroma: an updated experience through the last 10 years.
AB  - CONCLUSION: Rhinoscleroma is a chronic, specific, granuloma of the nose and other
      parts of the respiratory system. The disease is endemic in Egypt and many other
      countries. The causative organism is Klebsiella rhinoscleromatis bacillus, proved
      by fulfilling Koch's postulates. The mode of infection is not known and its
      worldwide irregular geographical distribution is not understood. Lines of
      treatment are unsatisfactory and a tendency for recurrence is the rule.
      OBJECTIVES: Our aim was to study the clinical presentation, microbiology,
      pathological staging, follow-up, and lines of treatment of new rhinoscleroma
      patients admitted or seen at Alexandria Main University Hospital from January
      1999 until January 2009. METHODS: Demographic data and the results of clinical,
      bacteriological, and histological examinations were reviewed. Medical and
      surgical treatments were evaluated. Follow-up as regards the results of treatment
      and incidence of recurrence was assessed. RESULTS: Fifty-six patients were
      included in the study. There were 26 males and 30 females, and 85% of patients
      presented in the third and fourth decades of life. The nose was affected in 100%
      of patients. Other regions affected were the nasopharynx in 13 patients, palate
      in 7 patients, skin in 2 patients, larynx in 3 patients, trachea in 17 patients,
      nasolacrimal duct in 2 patients, and premaxilla in 1 patient. No lymph node
      affection was reported. Klebsiella rhinoscleromatis strain III was isolated from
      100% of patients. Antibiotics used were a combination of trimethoprim
      sulfamethoxazole 400 mg and rifampicin 300 mg twice daily for 3 months. Since
      2003, this was replaced by ciprofloxacin 500 mg twice daily for 3 months.
      Surgical procedures performed were removal of nasal granulations, bronchoscopic
      dilatation, bipolar coagulation of skin lesions, tracheostomy, and repair of
      pharyngeal stenosis. Results were disappointing, as a large number of patients
      did not attend for follow-up. A high incidence of recurrence was found, reaching
      up to 25% within 10 years.

PMID- 21198343
TI  - Influence of aging over 10 years on auditory and vestibular functions in three
      patients with auditory neuropathy.
AB  - The influence of aging on hearing and vestibular function in patients with
      auditory neuropathy has not been investigated. The purpose of this study was to
      investigate how hearing and vestibular function in this disease change with
      aging. The subjects were three female patients with auditory neuropathy. We
      checked their hearing and vestibular function by speech discrimination tests,
      ABR, ECochG, DPOAE, caloric test, damped-rotational chair test, and VEMPs. In all
      three patients, speech discrimination ability and vestibular function markedly
      declined with aging. However, speech language understanding and higher brain
      function were less affected by aging.

PMID- 21198344
TI  - Therapeutic window for ferulic acid protection against noise-induced hearing loss
      in the guinea pig.
AB  - CONCLUSION: Our results are in agreement with the general idea that natural
      antioxidants achieve their best cytoprotective capacity if given before and soon
      after the stressor. OBJECTIVE: We focused on ferulic acid (FA, 4-hydroxy 3
      methoxycinnamic acid), a phenolic compound that is known to exhibit antioxidant
      properties. Our study was designed to evaluate the effectiveness of FA for
      different schedules of treatment to establish the 'therapeutic window' for FA
      protection. METHODS: Guinea pigs were exposed to acoustic trauma (6 kHz at 120 dB
      for 60 min) and received a total dose of 600 mg/kg of FA. Group I, noise control;
      group II, noise + FA (150 mg/kg) for 4 days starting 24 h post exposure; group
      III, noise + FA (60 mg/kg) 1 h before and 9 days post exposure; group IV, noise +
      FA (60 mg/kg) given 3 days before and 7 days post exposure; group V, noise + FA
      (150 mg/kg) 1 h before and 3 days post noise exposure. Auditory brainstem
      response (ABR) test and immunohistochemical and morphological studies were
      performed. RESULTS: Group V had significantly decreased noise-induced hearing
      loss at day 21 from noise exposure. The improvement of auditory function by FA
      was paralleled by a significant reduction in oxidative stress marker. The other
      schedules of drug administration showed a minor degree of protection.

PMID- 21198345
TI  - Total septal preservation for sellar approach - paving the way for future flap
      reconstructions.
AB  - CONCLUSIONS: Despite being a single surgical channel this approach provides
      enough room and maneuverability for microscopic and endoscopic surgery of sellar
      lesions and the total septal preservation technique allows future reconstructions
      using the posterior nasoseptal flap. OBJECTIVES: To demonstrate the importance
      and feasibility of total nasal septum and anterior sphenoid preservation in
      transseptal approaches to the sella. METHODS: Retrospective evaluation of 15
      transseptal approaches for sellar lesions with or without suprasellar extensions
      operated under general anesthesia with a total septal preservation technique.
      RESULTS: In all patients operated by this method a complete microscopic and
      endoscopic tumor removal was possible and an uneventful recovery was observed.
      Nasal congestion was mild and no episode of nasal bleeding, cerebrospinal leaks,
      visual loss, diabetes insipidus or death was observed. Breathing was considered
      normal or improved in all patients after removal of splints; this subjective
      sensation was confirmed at 1 month and 6 months follow-up visits. No external
      nose deformities or septal deviations were observed; nasal endoscopy demonstrated
      a preserved septum and anterior sphenoid wall anatomy on both sides of the nose
      at 1 month and 6 months follow-up visits. CT scans taken at 6 months after the
      procedure confirmed these clinical findings.

PMID- 21198346
TI  - Endolymphatic hydrops and blood-labyrinth barrier in Meniere's disease.
AB  - CONCLUSIONS: The blood-labyrinth barrier is impaired in association with the
      hydrops grade in Meniere's disease. OBJECTIVES: To investigate the relationship
      between endolymphatic hydrops and the clinical characteristics of patients with
      Meniere's disease revealed by 3 T magnetic resonance imaging (MRI). METHODS: A
      double dose of gadoteridol (Gd; 0.2 mmol/kg) was injected intravenously in 12
      patients with Meniere's disease. We performed three-dimensional fluid attenuated
      inversion recovery MRI and three-dimensional real inversion recovery MRI 4 h
      later using a 3 T MRI unit. Ten patients had unilateral and two had bilateral
      Meniere's disease. RESULTS: Fourteen ears with Meniere's disease showed intense
      Gd contrast on MRI compared with that in the 10 asymptomatic contralateral ears
      of patients with unilateral Meniere's disease (1.12 +/- 0.36 vs 0.82 +/- 0.15).
      The hydrops grade was correlated significantly with the contrast effect. The 14
      ears with Meniere's disease had endolymphatic hydrops. Of the 10 contralateral
      ears of patients with unilateral Meniere's disease, 2 had endolymphatic hydrops
      in the cochlea and 6 had endolymphatic hydrops in the vestibule.

PMID- 21198348
TI  - Prevalent nosocomial clusters among causative agents for candidemia in Hamilton,
      Canada.
AB  - In Canada, the incidence of candidemia, the bloodstream infection caused by
      Candida species, varied from 1.2-5.1 cases/100,000, representing the third most
      common type of bloodstream infections in intensive care unit patients. However,
      the relative contributions of nosocomial transmission in candidemia remain poorly
      understood. In this study, we investigated the prevalence of nosocomial clusters
      among the causative agents for candidemia in Hamilton, Ontario, Canada, during a
      period from January 2005 to February 2009. We genotyped 134 isolates from 125
      unrelated patients with candidemia, among which were 87 C. albicans, 20 C.
      parapsilosis, 11 C. glabrata, 15 C. tropicalis, and one C. krusei. Our PCR
      fingerprinting analyses using three highly polymorphic primers identified a total
      of 99 genotypes, with 18 of them shared by 44 independent isolates. Nine pairs of
      isolates were obtained from the same patients at the same time and each pair had
      identical fingerprints. Interestingly, all 44 independent strains belonging to
      each of the shared genotypes were isolated from patients within 3-months stay in
      the Hamilton hospitals. Both inter- and intra-ward clusters were found, including
      one that contained strains from intensive care units in two hospitals. Our
      results indicated that 33% of the patients with candidemia were infected by
      nosocomial clusters and suggested that measures should be taken in hospitals to
      prevent nosocomial acquisition of Candida infections.

PMID- 21198347
TI  - Prevalence of Candida bracarensis and Candida nivariensis in a Spanish collection
      of yeasts: comparison of results from a reference centre and from a population
      based surveillance study of candidemia.
AB  - Two new species related to Candida glabrata, i.e., Candida nivariensis and
      Candida bracarensis, have been proposed. The occurrence of these species among
      isolates collected in a Spanish mycology reference laboratory in 2008-2009 was
      reviewed. In addition, strains recovered as part of an active population-based
      surveillance of candidemia conducted in Barcelona between 2002 and 2003 were also
      analyzed. Among 143 clinical isolates received in 2008-2009, three (2%) were
      identified as C. bracarensis and none as C. nivariensis through sequencing of
      their ribosomal DNA. Of the 31 strains initially identified as C. glabrata in the
      2002-2003 population-based study (0.38 cases/100,000 population), none were found
      to belong to these related new species. Results from in vitro susceptibility
      studies of C. bracarensis isolates were comparable to those found with C.
      glabrata. Since new and cryptic species have been described, periodic
      surveillance including the use of molecular identification methods seems to be
      necessary in order to determine their frequency, geographical distribution and
      susceptibility profile.

PMID- 21198349
TI  - A comparative study of dermatophyte infections in Bursa, Turkey.
AB  - A total of 555 specimens from 372 patients with symptoms compatible with
      superficial mycosis were included in this study. Those from patients clinically
      diagnosed as having dermatomycosis were thoroughly investigated by mycological
      examinations in the laboratory, including microscopic studies of KOH mounts and
      cultivation of the samples in culture. The results of this study and a previous
      study in our hospital conducted in 1980 were compared with respect to clinical
      presentation and etiological agents. Onychomycosis was the most common clinical
      form of dermatomycoses, and Trichophyton rubrum was the most common pathogen in
      this study.

PMID- 21198350
TI  - Association of (GT)n repeats promoter polymorphism of heme oxygenase-1 gene with
      serum bilirubin levels in healthy Indian adults.
AB  - AIM: The present study was undertaken to investigate a length polymorphism of
      (GT)n repeats of the heme oxygenase-1 (HMOX-1) gene and its association with
      serum bilirubin levels in apparently healthy adults. METHODS: A total of 211
      individuals (normal hematology and liver function test) with bilirubin levels of
      1.7 to 22.2 MUM were studied. The (GT)n repeats were analyzed by PCR and
      subsequent sizing by capillary electrophoresis on the ABI Prism 310 Genetic
      Analyzer. RESULTS: Polymorphisms of the (GT)n repeats were grouped into three
      classes: short (S) alleles (<20 repeats), intermediate (M) alleles (20-28
      repeats), and long (L) alleles (>= 29 repeats). The frequencies of the S, M, and
      L allele groups were 0.10, 0.49, and 0.41, respectively. Carriers of short
      alleles had significantly higher mean bilirubin levels (13.8 +/- 5.10 MUM)
      compared with others (9.18 +/- 3.73 MUM, p < 0.001). CONCLUSION: Short (GT)n
      alleles of the HMOX-1 gene promoter could be a genetic risk factor for
      hyperbilirubinemia.

PMID- 21198351
TI  - Role of promyelocytic leukemia protein in host antiviral defense.
AB  - Several pathways have been implicated in the establishment of antiviral state in
      response to interferon (IFN), one of which implicates the promyelocytic leukemia
      (PML) protein. The PML gene has been discovered 20 years ago and has led to new
      insights into oncogenesis, apoptosis, cell senescence, and antiviral defense. PML
      is induced by IFN, leading to a marked increase of expression of PML isoforms and
      the number of PML nuclear bodies (NBs). PML is the organizer of the NBs that
      contains at least 2 permanent NB-associated proteins, the IFN-stimulated gene
      product Speckled protein of 100 kDa (Sp100) and death-associated dead protein
      (Daxx), as well as numerous other transient proteins recruited in these
      structures in response to different stimuli. Accumulating reports have implicated
      PML in host antiviral defense and revealed various strategies developed by
      viruses to disrupt PML NBs. This review will focus on the regulation of PML and
      the implication of PML NBs in conferring resistance to DNA and RNA viruses. The
      role of PML in mediating an IFN-induced antiviral state will also be discussed.

PMID- 21198352
TI  - The multifaceted interferon-inducible p200 family proteins: from cell biology to
      human pathology.
AB  - The interferon-inducible p200 family proteins consist of a group of homologous
      human and mouse proteins that have an N-terminal Pyrin domain and 1 or 2
      partially conserved 200 amino acid long C-terminal domains (designated the HIN
      domain or p200 X domain). These proteins display multifaceted activity due to
      their ability to bind to various target proteins (eg, transcription factors,
      signaling proteins, and tumor suppressor proteins) and modulate different cell
      functions. In addition to a role in interferon biology, increasing evidence
      supports a role for these proteins as regulators of various cell functions,
      including proliferation, differentiation, apoptosis, senescence, inflammasome
      assembly, and control of organ transplants. As a consequence, alterations in
      their expression and function may be of relevance in the pathogenesis of human
      diseases, such as systemic autoimmune syndromes, tumors, and degenerative
      diseases. This review summarizes the literature describing these data, highlights
      some of the important findings derived from recent studies, and speculates about
      future perspectives.

PMID- 21198353
TI  - Factors influencing children's judgments of overweight peers.
AB  - OBJECTIVE: This study assessed children's perceptions of an overweight or non
      overweight target of name-calling. METHODS: Participants were 4(th) and 5(th)
      grade students. Children selected a line drawing of an overweight or a non
      overweight child as a target. After this, they viewed each line drawing again and
      rated each child's social attraction, niceness, experience of negative emotions,
      size, and popularity (whether others would like the child). Finally, children
      provided ideas for improving acceptance of the line-drawing they selected as a
      target of name-calling. RESULTS: Findings from regression analyses indicated that
      children who reported higher levels of victimization and selected the overweight
      child as a target reported higher social attraction for this target. Children's
      weight status and their victimization interacted to influence ratings of niceness
      and negative emotions. Children reported that peers would like the overweight
      line drawing less than the non-overweight one. CONCLUSIONS: Children tended to
      report that an overweight child would be a target of name-calling and be less
      accepted. Our findings provided partial support for the idea that children's own
      victimization status influenced ratings of social attraction, niceness, and
      negative emotions. Longitudinal studies will provide information on change in
      perceptions over time.

PMID- 21198354
TI  - Changes in body mass index and health related quality of life from childhood to
      adolescence.
AB  - OBJECTIVE: To determine longitudinal relationships between body mass index (BMI)
      and health-related quality of life (HRQoL) in an adolescent population sample.
      Design. Data collected in 2000 and 2005 within the Health of Young Victorians
      longitudinal cohort study. SETTING: Originally a community sample of elementary
      school students in Victoria, Australia. Follow-up occurred in either secondary
      schools or individuals homes. PARTICIPANTS: Cohort recruited in 1997 via a random
      sampling design from Victorian elementary schools. Originally comprising 1 943
      children, 1 569 (80.8%) participated in 2000 (wave 2, 8-13 years) and 851 (54%)
      in 2005 (wave 3, 13-19 years). Main outcome measures. In both waves participants
      and their parents completed the PedsQL, a 23-item child HRQoL measure, and BMI z
      scores and status (non-overweight, overweight or obese) were calculated from
      measured height and weight. Associations were tested cross-sectionally and
      longitudinally (linear regression, adjusted for baseline values) RESULTS: A total
      of 81.6% remained in the same BMI category, while 11.4% and 7.0% moved to higher
      and lower categories, respectively. Cross-sectional inverse associations between
      lower PedsQL and higher BMI categories were similar to those for elementary
      school children. Wave 2 BMI strongly predicted wave 3 BMI and wave 2 PedsQL
      strongly predicted wave 3 PedsQL. Only parent-reported Total PedsQL score
      predicted higher subsequent BMI, though this effect was small. Wave 2 BMI did not
      predict wave 3 PedsQL. CONCLUSIONS: This novel study confirmed previous cross
      sectional associations, but did not provide convincing evidence that BMI is
      causally associated with falling HRQoL or vice versa across the transition from
      childhood to adolescence.

PMID- 21198355
TI  - Toll-like receptors as interferon-regulated genes and their role in disease.
AB  - The Toll-like receptors (TLRs) are innate sensors that recognize both microbial
      and endogenous ligands, initiating the host defense response. TLRs initiate the
      potent proinflammatory response to infection, are the target for adjuvants, and
      are essential for the establishment and maturation of adaptive immunity. As such
      they have been the interest of widespread research and the target of therapeutic
      intervention on multiple diseases. It has become apparent that expression of a
      subset of TLRs (TLR1, TLR2, TLR3, TLR5, and TLR7) is induced by Type I
      interferons (IFN). The role and impact of IFN expression on TLR responses is
      therefore critical in understanding the role of TLRs in disease, particularly as
      IFN itself is a downstream gene induced by specific TLRs. In this review we
      discuss the function and role of IFN-regulated TLRs in disease and how the role
      of IFN may impact upon TLR induction of the immune response in diseases,
      particularly in mouse models.

PMID- 21198356
TI  - Laparoscopic renal descensus for upper tract reconstruction.
AB  - We describe a modern use of laparoscopic renal descensus during the
      reconstruction of the upper urinary tract. The patient is a 76-year-old
      mononephric man with recurrent carcinoma in situ in the distal ureter. Using the
      described technique, we produced an additional 8 to 10 cm of ureteral length and
      performed a simple ureteroneocystotomy instead of using a traditional psoas hitch
      and Boari flap creation, bowel interposition, or autotransplantation.
      Laparoscopic renal descensus is an uncommonly used but simple procedure that may
      prevent the need for bladder mobilization or Boari flap creation, particularly in
      the setting of a hostile pelvis.

PMID- 21198357
TI  - Child obesity and fitness levels among Kenyan and Canadian children from urban
      and rural environments: a KIDS-CAN Research Alliance Study.
AB  - OBJECTIVE: This study was designed to gather anthropometric and fitness-related
      data on Kenyan children living in urban (UKEN) and rural (RKEN) environments and
      to compare them with previous data collected on Canadian children in order to
      examine the potential nutrition-physical activity transition. METHODS: Height,
      weight, waist circumference, triceps skinfolds were directly measured on rural
      (RKEN) and urban Kenyan (UKEN) children (n = 179, 9-13 years) and compared with
      existing data from Canadian children living in urban and rural environments (n =
      274, 9-13 years). Aerobic fitness was measured using the 20 m shuttle run,
      flexibility using the sit-and-reach test and isometric handgrip strength was
      assessed. RESULTS: None of the RKEN children were overweight or obese (OWO).
      However, 6.8% of UKEN boys and 16.7% of girls were OWO. The RKEN children had
      lower BMI, waist circumference, and triceps skinfolds than all other groups
      (UKEN, and Canadian: p < 0.05). UKEN children were leaner than Canadian children
      (p < 0.05). Male and female RKEN children had higher running speeds, and aerobic
      fitness than UKEN children (p < 0.001). Isometric strength was not different
      between Kenyan groups and was not different from urban living Canadian children.
      UKEN children were the least flexible group, and girls were more flexible than
      boys in all groups. CONCLUSIONS: Urban Kenyan children appear to be showing signs
      of the nutrition-physical activity transition, as judged by the anthropometric
      similarities to contemporary living Canadian children. Further support is
      provided by examining the difference in prevalence of overweight/obesity among
      UKEN compared with their RKEN counterparts and their lower aerobic fitness level.

PMID- 21198358
TI  - Molecular epidemiology of Plum pox virus in Japan.
AB  - For a molecular epidemiological study based on complete genome sequences, 37 Plum
      pox virus (PPV) isolates were collected from the Kanto region in Japan. Pair-wise
      analyses revealed that all 37 Japanese isolates belong to the PPV-D strain, with
      low genetic diversity (less than 0.8%). In phylogenetic analysis of the PPV-D
      strain based on complete nucleotide sequences, the relationships of the PPV-D
      strain were reconstructed with high resolution: at the global level, the
      American, Canadian, and Japanese isolates formed their own distinct monophyletic
      clusters, suggesting that the routes of viral entry into these countries were
      independent; at the local level, the actual transmission histories of PPV were
      precisely reconstructed with high bootstrap support. This is the first
      description of the molecular epidemiology of PPV based on complete genome
      sequences.

PMID- 21198359
TI  - Longitudinal association between IGFBP-1 levels and parameters of the metabolic
      syndrome in obese children before and after weight loss.
AB  - BACKGROUND: Insulin-like growth factor binding protein 1 (IGFBP-1) is a marker of
      insulin resistance. We hypothesized that IGFBP-1 is associated with the metabolic
      syndrome (MetS), which is related to insulin resistance. METHODS: We examined 51
      obese Caucasian children (mean age 12.1 ? 2.3, 55% male, mean body mass index
      [BMI] 31.8 ? 4.8 kg/m(2)). Anthropometrical markers, pubertal stage, hepatic
      ultrasound, waist circumference, blood pressure, fasting serum IGFBP-1, IGFBP-3,
      IGF-I, adiponectin, leptin, transaminases, glucose, insulin, triglycerides, and
      HDL-cholesterol concentrations were determined at onset and the end of the one
      year lifestyle intervention. RESULTS: In contrast to IGF-I and IGFBP-3, IGFBP-1
      correlated significantly to most parameters of the MetS in cross-sectional (waist
      circumference: r = -0.45, triglycerides: r = -0.29; insulin: r = -0.31; HOMA: r =
      -0.30) and longitudinal analyses (? triglycerides: r = ?0.22; ? Insulin: r =
      ?0.25; ? HOMA: r = ?0.62). The association between changes of HOMA and changes of
      IGFBP-1 was stronger than the associations between changes of leptin or
      adiponectin, and changes of HOMA. The risk for the MetS was inversely related to
      IGFBP-1 levels (odds ratio:-0.05 per additional IGFBP-1 unit; 95% confidence
      interval: -0.08 up to -0.02; p = 0.019) in a multiple logistic regression
      analyses adjusted to BMI, pubertal stage, age, and gender. The nine obese
      children with the MetS had significantly lower IGFBP-1 levels (1.6 ? 1.3 ngm/l)
      than the 42 obese children without the MetS (4.0 ? 3.8 ng/ml). The eleven obese
      children with fatty liver assessed by ultrasound had significantly lower IGFBP-1
      levels (1.5 ? 1.3 ngm/l) than the 40 obese children without fatty liver (4.2 ?
      4.1 ng/ml). CONCLUSION: The strong relationships between IGFBP-1, insulin
      resistance, and the MetS suggest that IGFBP-1 might be a promising marker for
      these entities in obesity. This study is registered at clinicaltrials.gov
      (NCT00435734).

PMID- 21198360
TI  - Bacterial effector HopF2 suppresses arabidopsis innate immunity at the plasma
      membrane.
AB  - Many bacterial pathogens inject a cocktail of effector proteins into host cells
      through type III secretion systems. These effectors act in concert to modulate
      host physiology and immune signaling, thereby promoting pathogenicity. In a
      search for additional Pseudomonas syringae effectors in suppressing plant innate
      immunity triggered by pathogen or microbe-associated molecular patterns (PAMPs or
      MAMPs), we identified P. syringae tomato DC3000 effector HopF2 as a potent
      suppressor of early immune-response gene transcription and mitogen-activated
      protein kinase (MAPK) signaling activated by multiple MAMPs, including bacterial
      flagellin, elongation factor Tu, peptidoglycan, lipopolysaccharide and HrpZ1
      harpin, and fungal chitin. The conserved surface-exposed residues of HopF2 are
      essential for its MAMP suppression activity. HopF2 is targeted to the plant
      plasma membrane through a putative myristoylation site, and the membrane
      association appears to be required for its MAMP-suppression function. Expression
      of HopF2 in plants potently diminished the flagellin-induced phosphorylation of
      BIK1, a plasma membrane-associated cytoplasmic kinase that is rapidly
      phosphorylated within one minute upon flagellin perception. Thus, HopF2 likely
      intercepts MAMP signaling at the plasma membrane immediately of signal
      perception. Consistent with the potent suppression function of multiple MAMP
      signaling, expression of HopF2 in transgenic plants compromised plant nonhost
      immunity to bacteria P. syringae pv. Phaseolicola and plant immunity to the
      necrotrophic fungal pathogen Botrytis cinerea.

PMID- 21198361
TI  - The plant growth-promoting rhizobacterium Bacillus cereus AR156 induces systemic
      resistance in Arabidopsis thaliana by simultaneously activating salicylate- and
      jasmonate/ethylene-dependent signaling pathways.
AB  - Bacillus cereus AR156 is a plant growth-promoting rhizobacterium that induces
      resistance against a broad spectrum of pathogens including Pseudomonas syringae
      pv. tomato DC3000. This study analyzed AR156-induced systemic resistance (ISR) to
      DC3000 in Arabidopsis ecotype Col-0 plants. Compared with mock-treated plants,
      AR156-treated ones showed an increase in biomass and reductions in disease
      severity and pathogen density in the leaves. The defense-related genes PR1, PR2,
      PR5, and PDF1.2 were concurrently expressed in the leaves of AR156-treated
      plants, suggesting simultaneous activation of the salicylic acid (SA)- and the
      jasmonic acid (JA)- and ethylene (ET)-dependent signaling pathways by AR156. The
      above gene expression was faster and stronger in plants treated with AR156 and
      inoculated with DC3000 than that in plants only inoculated with DC3000. Moreover,
      the cellular defense responses hydrogen peroxide accumulation and callose
      deposition were induced upon challenge inoculation in the leaves of Col-0 plants
      primed by AR156. Also, pretreatment with AR156 led to a higher level of induced
      protection against DC3000 in Col-0 than that in the transgenic NahG, the mutant
      jar1 or etr1, but the protection was absent in the mutant npr1. Therefore, AR156
      triggers ISR in Arabidopsis by simultaneously activating the SA- and JA/ET
      signaling pathways in an NPR1-dependent manner that leads to an additive effect
      on the level of induced protection.

PMID- 21198362
TI  - Inoculation- and nitrate-induced CLE peptides of soybean control NARK-dependent
      nodule formation.
AB  - Systemic autoregulation of nodulation in legumes involves a root-derived signal
      (Q) that is perceived by a CLAVATA1-like leucine-rich repeat receptor kinase
      (e.g. GmNARK). Perception of Q triggers the production of a shoot-derived
      inhibitor that prevents further nodule development. We have identified three
      candidate CLE peptide-encoding genes (GmRIC1, GmRIC2, and GmNIC1) in soybean
      (Glycine max) that respond to Bradyrhizobium japonicum inoculation or nitrate
      treatment. Ectopic overexpression of all three CLE peptide genes in transgenic
      roots inhibited nodulation in a GmNARK-dependent manner. The peptides share a
      high degree of amino acid similarity in a 12-amino-acid C-terminal domain, deemed
      to represent the functional ligand of GmNARK. GmRIC1 was expressed early (12 h)
      in response to Bradyrhizobium-sp.-produced nodulation factor while GmRIC2 was
      induced later (48 to 72 h) but was more persistent during later nodule
      development. Neither GmRIC1 nor GmRIC2 were induced by nitrate. In contrast,
      GmNIC1 was strongly induced by nitrate (2 mM) treatment but not by Bradyrhizobium
      sp. inoculation and, unlike the other two GmCLE peptides, functioned locally to
      inhibit nodulation. Grafting demonstrated a requirement for root GmNARK activity
      for nitrate regulation of nodulation whereas Bradyrhizobium sp.-induced
      regulation was contingent on GmNARK function in the shoot.

PMID- 21198363
TI  - Evaluation of a standardized wellness protocol to improve anthropometric and
      physiologic function and to reduce health risk factors: a retrospective analysis
      of outcome.
AB  - OBJECTIVES: The objective of this study was to determine whether a standardized,
      commercial wellness protocol (Creating Wellness) that focuses on diet, exercise,
      vitamin supplementation, and one-on-one coaching improves anthropometric and
      physiologic function and reduces health risk factors. METHODS: Using a
      retrospective analysis of subject data collected through a central data
      repository, several measures of anthropometric and physiologic function were
      analyzed for changes in outcome. RESULTS: There were 197 private chiropractic
      clinics in the United States utilizing the Creating Wellness protocol in 2007. A
      total of 178 subjects completed an 18-week protocol and had initial and final
      assessments. All anthropometric and physiologic measures showed improvement
      following the intervention; therefore, this standardized wellness protocol was
      shown to improve weight, heart rate, blood pressure, strength, body-mass index,
      and forced vital capacity. Paired sample t tests and significance testing for the
      entire sample, and for both genders separately, determined that these changes
      were statistically significant. CONCLUSIONS: The Creating Wellness protocol leads
      to improved health risk factor outcomes based on improvement in anthropometric
      and physiologic measures in this study population. The results of these tests are
      generally accepted measures of risk for cardiovascular events, diabetes,
      metabolic syndrome, and cancer. There are little evaluative data on health
      outcomes related to programs designed to reduce risk of lifestyle-related
      diseases. For those clients utilizing the program evaluated in this study, there
      appears to be evidence suggesting improved health risk factor outcomes from
      participation in this specific protocol. The results of this study have
      implications related to a broad number of public health issues related to
      management of chronic lifestyle diseases.

PMID- 21198364
TI  - Gaming across different consoles: exploring the influence of control scheme on
      game-player enjoyment.
AB  - Many studies have investigated how different technological features impact the
      experience of playing video games, yet few have focused on how control schemes
      may affect the play experience. This research employed a between-subjects design
      to explore the relationship between the type of console played (Nintendo Wii,
      Playstation 2) and feelings of flow and enjoyment during the game-play
      experience. Results indicated that participants reported greater feelings of
      control and enjoyment with a traditional control scheme (Playstation 2) than with
      the more technologically advanced control scheme (Nintendo Wii). Further
      mediation analysis showed that enjoyment was driven by the sense of control that
      participants experienced and not simply by whether they won the game. Theoretical
      and practical implications are discussed.

PMID- 21198365
TI  - Effects of cell-phone and text-message distractions on true and false
      recognition.
AB  - This study examined the effects of electronic communication distractions,
      including cell-phone and texting demands, on true and false recognition,
      specifically semantically related words presented and not presented on a computer
      screen. Participants were presented with 24 Deese-Roediger-McDermott (DRM) lists
      while manipulating the concurrent presence or absence of cell-phone and text
      message distractions during study. In the DRM paradigm, participants study lists
      of semantically related words (e.g., mother, crib, and diaper) linked to a non
      presented critical lure (e.g., baby). After studying the lists of words,
      participants are then requested to recall or recognize previously presented
      words. Participants often not only demonstrate high remembrance for presented
      words (true memory: crib), but also recollection for non-presented words (false
      memory: baby). In the present study, true memory was highest when participants
      were not presented with any distraction tasks during study of DRM words, but
      poorer when they were required to complete a cell-phone conversation or text
      message task during study. False recognition measures did not statistically vary
      across distraction conditions. Signal detection analyses showed that participants
      better discriminated true targets (list items presented during study) from true
      target controls (items presented during study only) when cell-phone or text
      message distractions were absent than when they were present. Response bias did
      not vary significantly across distraction conditions, as there were no
      differences in the likelihood that a participant would claim an item as "old"
      (previously presented) rather than "new" (not previously presented). Results of
      this study are examined with respect to both activation monitoring and fuzzy
      trace theories.

PMID- 21198366
TI  - The measurement of cyberbullying: dimensional structure and relative item
      severity and discrimination.
AB  - In relation to a sample of 1,092 Italian adolescents (50.9% females), the present
      study aims to: (a) analyze the most parsimonious structure of the cyberbullying
      and cybervictimization construct in male and female Italian adolescents through
      confirmatory factor analysis; and (b) analyze the severity and the discrimination
      parameters of each act using the item response theory. Results showed that the
      structure of the cyberbullying scale for perpetrated and received behaviors in
      both genders could best be represented by a monodimensional model where each item
      lies on a continuum of severity of aggressive acts. For both genders, the less
      severe acts are silent/prank calls and insults on instant messaging, and the most
      severe acts are unpleasant pictures/photos on Web sites, phone
      pictures/photos/videos of intimate scenes, and phone pictures/photos/videos of
      violent scenes. The items nasty text messages, nasty or rude e-mails, insults on
      Web sites, insults in chatrooms, and insults on blogs range from moderate to high
      levels of severity. Regarding the discrimination level of the acts, several items
      emerged as good indicators at various levels of cyberbullying and
      cybervictimization severity, with the exception of silent/prank calls.
      Furthermore, gender specificities underlined that the visual items can be
      considered good indicators of severe cyberbullies and cybervictims only in males.
      This information can help in understanding better the nature of the phenomenon,
      its severity in a given population, and to plan more specific prevention and
      intervention strategies.

PMID- 21198374
TI  - LOC387761 polymorphism is associated with type 2 diabetes in the Mexican
      population.
AB  - Worldwide researchers have invested time, effort, and money during the last years
      to find new genes associated with diabetes susceptibility, such as LOC387761,
      HHEX, EXT2, and SLC30A8. The aim of the present study was to evaluate whether
      single-nucleotide polymorphisms (SNPs) of these genes are associated with type 2
      diabetes (T2D) and metabolic traits in the Mexican population. We also assessed
      these SNPs in Mexican indigenous groups to identify a possible inherited
      susceptibility. Seven SNPs were analyzed in 789 Mexicans (234 control subjects,
      455 type 2 diabetic patients, and 100 of indigenous origin), using the KASPar
      assay (KBioscience Company). Analysis of the data showed an association of the
      LOC387761 SNP rs7480010 with T2D (p = 0.019). The risk allele A of rs7480010
      increased body mass index in diabetic patients (p = 0.01). In addition, there was
      no association between T2D and the SNPs of HHEX, EXT2, and SLC30A8. Our findings
      suggest that the SNP rs7480010 (LOC387761) can contribute to a failure in insulin
      secretion, thus increasing the susceptibility to T2D in Mexicans.

PMID- 21198375
TI  - First prize: Standard laparoscopic donor nephrectomy versus laparoendoscopic
      single-site donor nephrectomy: a randomized comparative study.
AB  - INTRODUCTION: The purpose of this study was to compare in a randomized fashion
      the clinical outcomes following standard laparoscopic and laparoendoscopic single
      site (LESS) donor nephrectomies. MATERIALS AND METHODS: Fifty voluntary renal
      donors who met the inclusion and exclusion criteria were randomized to standard
      laparoscopic (group A) and LESS (group B) donor nephrectomies. The primary end
      point of the study was patients' postoperative pain. The clinical outcomes,
      patient's quality of life, body image, and cosmetic scores on follow-up were also
      compared. RESULTS: The operating times were similar in both groups (175.83 +/-
      47.57 vs. 172.20 +/- 38.33 minutes, p = 0.38). The surgeon's difficulty as
      measured using a visual analog scale was significantly more in group B in 4 of 10
      defined steps. The postoperative patient pain scores were similar till 48 hours
      following surgery (3.84 +/- 1.68 vs. 3.68 +/- 0.75, p = 0.33), but following
      which the patients in group B had improved pain scores (2.08 +/- 0.91 vs. 1.24 +/
      0.72, p = 0.0004). Analgesic requirements were similar in both groups (p =
      0.47). The warm ischemia times in group B (5.11 +/- 1.01 vs. 7.15 +/- 1.84
      minutes, p < 0.0001) were longer but the total ischemia times in both groups were
      similar (62.55 +/- 9.46 vs. 62.71 +/- 12.14 minutes, p = 0.48). All grafts had on
      table urine output in the recipient. Intraoperative (8% vs. 16%, p = 0.2) and
      postoperative complications (20% vs. 16%, p = 0.99) in both groups were
      comparable. The patients in group B had shorter hospital stay (4.56 +/- 0.82 vs.
      3.92 +/- 0.76 days, p = 0.003). There was no graft loss in either group except
      for one recipient in group A who sustained sudden cardiac death. The estimated
      glomerular filtration rates of recipients at 1 year were comparable for both
      groups (80.87 +/- 22.12 vs. 81.51 +/- 29.01 mL/minute, p = 0.46). The donor's
      quality of life, body image, and cosmetic scores were comparable for both groups.
      CONCLUSION: In this select group of donors, LESS donor nephrectomy, although
      challenging to the surgeon with longer warm ischemic times, gave early pain
      relief with shorter hospital stay and comparable graft function.

PMID- 21198376
TI  - Characterization of Y-chromosomal short tandem repeat markers in Pakistani
      populations.
AB  - The Y chromosome microsatellite markers have been extensively used for population
      genetic studies and in individual identification and paternity testing in
      forensic medicine. In the present study, we report the data of five male
      specific, polymorphic microsatellites in 740 unrelated male individuals from 12
      different ethnic groups of Pakistan. The overall diversities of these individual
      loci in Pakistan ranged from 0.236 to 0.799. The total haplotypes identified were
      152, and of these, 70 different haplotypes were present in only single
      individuals. Two haplotypes were found more frequently, 9_8_17_11_24 (13.5%) and
      9_8_17_11_25 (8.6%), showing population-specific clustering in the Mohanna and
      the Brahui, respectively. An overall haplotype diversity of 0.965 in Pakistan
      suggested a high power of discrimination for these loci. Few populations,
      particularly the Mohanna and the Balti, showed lower haplotype diversity values
      for these loci (0.662 and 0.758, respectively). This set of microsatellite loci
      reported in the study can be used for population genetics and forensic medicine
      analysis. This study also demonstrates the importance of studying haplotype
      distribution pattern in population genetics.

PMID- 21198377
TI  - Evaluation of Aurora-A gene polymorphism and esophageal cancer risk in a South
      Indian population.
AB  - AIM: Aurora-A is a serine/threonine protein kinase that functions in centrosome
      maturation and spindle assembly and is involved in regulating chromosome
      segregation. It is amplified and overexpressed in several human cancers. The aim
      of the present study was to assess the role of T91A Aurora-A gene polymorphism
      associated with aneuploidy in human tumors. RESULT: Patients with different upper
      gastrointestinal tract symptoms who were referred for endoscopy were studied.
      They were categorized as individuals with esophageal cancer, esophagitis, and
      normal endoscopy based on endoscopy and histology reports. Healthy volunteers
      were used as controls for carrying out genomic polymerase chain reaction followed
      by restriction digestion. The cancer and esophagitis groups showed a higher
      percentage of cases with the TA genotype compared with the controls and
      gastrointestinal tract normal endoscopy samples. However, only esophagitis,
      despite a small sample size, showed a statistically significant association with
      the TA genotype (odds ratio=3.6082, 95% class interval=1.1276-8.8346, p=0.0411).
      It was also assessed if the T91A polymorphism plays a role in enhancing the
      effects of exogenous factors such as smoking, alcohol, tea, betel chewing, and
      nonvegetarian diet in esophageal pathologies. CONCLUSION: Our results indicate
      that the TT genotype is protective against these factors as a higher percentage
      of this genotype was found in individuals with normal endoscopy. This is the
      first study, to the best of our knowledge, carried out in an Indian population to
      evaluate the association of Aurora-A gene polymorphism with esophageal cancer.

PMID- 21198378
TI  - A novel SNaPshot assay to detect genetic mutations related to iron metabolism.
AB  - The minisequencing method is a cost-effective tool to study single-nucleotide
      polymorphisms in human disease. For this reason, a novel polymerase chain
      reaction multiplex SNaPshot reaction has been developed that targets 10 autosomal
      mutations in genes, or regions near to them, reported to be involved in iron
      metabolism: TMPRSS6, TF, and HFE. To validate this multiplex, 284 samples from
      unrelated women from the Spanish population were tested at a fertile age. The
      novel polymerase chain reaction multiplex SNaPshot reaction developed is a very
      simple, sensitive, and low-cost approach, and therefore will be useful as a tool
      of clinic diagnosis in iron metabolism alterations and to replicate results
      obtained from genome-wide linkage analysis.

PMID- 21198379
TI  - The Need for Patient-Subjective Data in the DSM and the ICD.
AB  - One improvement from the second to the third edition of the Diagnostic and
      Statistical Manual of Mental Disorders was to replace clinicians' subjective
      interpretations of mental disorders with objective descriptions of signs and
      symptoms that could be rated reliably across investigators. Along with
      clinicians' subjective impressions, however, the subjective experiences of the
      person with the mental disorder were minimized. This information could be
      valuable, as people's subjective experiences of disorders may indicate major
      underlying processes and be different from how characteristics of disorders
      appear objectively to outside observers. The authors suggest that empirically
      derived, patient-subjective characteristics of mental disorders be incorporated
      into future editions of the DSM and the ICD. Not only will these data offer
      important information that will help to enhance the accuracy of the diagnostic
      categories of the DSM and ICD, but such data also may serve to enhance
      clinicians' abilities to conceptualize accurately and empathically treat these
      disorders in their patients. Examples of patient-subjective criteria and their
      relationship to current DSM criteria are examined for borderline personality
      disorder and schizophrenia and suggestions for DSM-V and ICD-11 are offered.
      Diagnostic criteria that accurately reflect patients' subjective experience could
      also increase clinicians' ability to empathize with patients, one of the most
      important variables in treatment alliances.

PMID- 21198380
TI  - Patient Involvement in the Development of DSM-V.

PMID- 21198381
TI  - The data of diagnosis: new approaches to psychiatric classification.

PMID- 21198382
TI  - Patients' subjective experience as a component of psychiatric assessment: where
      does it fit?

PMID- 21198383
TI  - Commentary on "The Need for Patient-Subjective Data in the DSM and the ICD".

PMID- 21198384
TI  - The Use of Countertransference to Halt Psychiatry's Retreat from Patients.

PMID- 21198385
TI  - Depression in systemic lupus erythematosus: the key role of illness intrusiveness
      and concealment of symptoms.
AB  - Extant literature on depression in chronic illness points to the association
      between depression and increased morbidity (Moussavi et al., 2007). There is to
      date little research on the surmised reciprocal relationship between the two.
      This longitudinal study of 30 women suffering from systemic lupus erythematosus
      (SLE) was conducted using self-report measures as well as physical illness
      markers, in order to place depression among SLE patients within what is known of
      the psychosocial context of depression. The objective of this study was to
      differentiate between the broadly illness-related and personality-related aspects
      of SLE depression. Results show that depression is preceded by concealment of SLE
      symptoms and by illness intrusiveness, a concept reflecting the subjective
      illness experience. Furthermore, depression is shown to precede changes in
      illness intrusiveness. Thus, illness intrusiveness and symptom concealment - but
      not physical illness markers - emerge as key factors in understanding the co
      morbidity of SLE and depression. These findings, viewed within the methodological
      limitations of this study, indicate the centrality of perceptions, of the 'lived
      experience' of the illness, in the detection and treatment of depression among
      women with SLE.

PMID- 21198386
TI  - Hubris: a primal danger.
AB  - Although the myth of Oedipus has been linked with psychiatry through the words of
      Sigmund Freud, it has not been remembered in the context of its playwright's
      intention. Sophocles gave Oedipus to his fellow Athenians as a warning (Knox,
      1984). That warning was about hubris. This paper proposes that warnings about
      hubris have appeared on our phylogenetic radar. It concludes that these
      archetypal warnings have been essential for our species, as strivings for power
      and status endanger prosocial behaviors critical for survival. This idea has
      support from recent studies about cooperative behavior, fairness, and reciprocity
      that suggest we are predisposed to protect prosocial behaviors and punish that
      which threatens them. The paper ultimately encourages clinicians to differentiate
      between pride and hubris, related emotional states that drive very different
      motivational and goal-directed responses in moral decision-making.

PMID- 21198387
TI  - Long-term military work outcomes in soldiers who become mental health casualties
      when deployed on operations.
AB  - BACKGROUND: little is known about longer term military work outcomes in UK
      military personnel who develop mental health problems when operationally
      deployed. Deployed Field Mental Health Teams (FMHTs) who support them follow the
      principles of "Forward Psychiatry," aiming to treat psychiatric casualties close
      to the front line to maximize operational effectiveness and occupational
      retention. AIM: to examine the short- and long-term military work outcomes in
      soldiers deployed to Iraq between 2003 and 2007 who were referred to the FMHT.
      METHOD: FMHT clinical records were linked to occupational records with 825
      resulting matches. RESULTS: 71.6% of the referred soldiers with a documented
      short-term military work outcome returned to their operational unit, and 73.5% of
      those who had a documented long-term military work outcome served on for a period
      in excess of two years. Adjusting for potential confounders, a shorter service
      length and removal from the operational theatre were both strongly associated
      with premature discharge; however, it was not possible to determine the severity
      of the presenting mental health problem and assess whether this impacted outcome.
      CONCLUSIONS: the results of this study support the use of the Forward Psychiatry
      principles in achieving good short-term military work outcomes. Utilizing these
      principles, three-quarters of those referred to the FMHT were returned to their
      deployed unit and approximately three-quarters of those assessed by the FMHT
      remained in service two years after referral. We suggest that these are positive
      work outcomes; however, being evacuated out of the operational environment and
      having a short service length were both associated with premature discharge,
      though we were unable to examine the role of illness severity.

PMID- 21198388
TI  - The impact of psychiatric symptoms, interpersonal style, and coercion on
      aggression and self-harm during psychiatric hospitalization.
AB  - Interpersonal style, a key component of personality and personality disorder, has
      emerged as an important characteristic that is relevant to aggressive behavior by
      patients in psychiatric hospitals. However, studies examining the relationship
      between interpersonal style and aggression have thus far only been conducted with
      patients with personality disorder and/or mild and stable symptoms of mental
      illness. This study explored the relative importance of patients' interpersonal
      style, psychiatric symptoms, and perceptions of staff coercion on aggression and
      self-harm during acute psychiatric hospitalization. One hundred and fifty-two
      patients (M = 38.32 years, SD = 12.06; 56.8% males and 43.2% females) admitted
      for short-term assessment and treatment to the acute units of a civil and a
      forensic psychiatric hospital were administered the Brief Psychiatric Rating
      Scale, Impact Message Inventory, and MacArthur Admission Experience Survey.
      Participants' files were reviewed and nursing staff were interviewed at the end
      of each patient's hospital stay to determine whether participants had self-harmed
      or acted aggressively towards others. Initial univariate analyses showed that
      thought disorder and dominant and hostile-dominant interpersonal styles predicted
      aggression. Using multiple regression and controlling for gender and age, only a
      hostile-dominant interpersonal style predicted aggression (beta = .258, p < .05).
      No factors were significantly related to self-harm. These results suggest that
      measures of interpersonal style are sensitive to those aspects of interpersonal
      functioning that are critical to patient's responses to the demands of
      psychiatric in-patient treatment. Procedures to assess risk and engage and manage
      potentially aggressive patients, including limit-setting styles and de-escalation
      strategies, should take into account the interpersonal style of patients and the
      interpersonal behavior of staff.

PMID- 21198393
TI  - Molecular characterization of 25 Chinese pedigrees with 21-hydroxylase
      deficiency.
AB  - Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders
      mainly caused by a defect in the steroid 21-hydroxylase gene (CYP21A2). In this
      study, we investigated the molecular defects of 25 Chinese pedigrees with 21
      hydroxylase deficiency (21-OHD). Diagnosis of the probands in the families was
      based on their typical clinical presentations, such as inborn ambiguous
      genitalia, or early onset of salt wasting and biochemical metabolite
      abnormalities. All 10 exons and exon-intron boundaries of the CYP21A2 gene were
      amplified from the genomic DNA of the probands and then analyzed by direct
      sequencing. The phenotypes of the 26 patients from 25 pedigrees were classified
      as the classical form of 21-OHD. One novel mutation (c.1223 G>T) and 13 recurrent
      mutations of CYP21A2 were identified in the 25 pedigrees by genetic analysis. The
      novel c.1223 G>T mutation results in the substitution of arginine by leucine at
      amino acid position 408 (p.Arg408Leu). The most frequent mutation alleles were
      IVS2-13A/C>G (14/52) and I172N (11/52), followed by chimeric mutations (10/52).
      Forty six of 52 mutated alleles resulted from pseudogene conversion and 6 of 52
      from random mutations. The spectrum of CYP21A2 mutation in our study was slightly
      different from those previously reported in Chinese and in other ethnic groups of
      the world. Although microconversion events were the main cause of mutations in
      the CYP21 gene, random mutations with a common origin can also be the reason for
      21-OHD.

PMID- 21198394
TI  - Human leukocyte antigen-DQA1 gene allelic distribution: experience of a major
      tertiary care center in Lebanon.
AB  - AIMS: DQA1 is a human leukocyte antigen (HLA) class II molecule that is similar
      to the other class II molecules DR and DP. This study is the first of its kind to
      describe the distribution of HLA-DQA1 alleles in Lebanon. METHODS: HLA-DQA1
      typing was detected using the polymerase chain reaction/sequence-specific priming
      method in 111 Lebanese individuals referred for HLA typing and possible bone
      marrow donation. RESULTS: Our data was compared to that of several populations.
      Some similarities were found between the Lebanese, Tunisian, Spanish, and Kuwaiti
      populations. CONCLUSION: This very first report from Lebanon will be of great
      help for later research to study the association of DQA1 alleles with major
      diseases in the Lebanese population and will add to the published international
      literature related to this important histocompatibility locus.

PMID- 21198395
TI  - Spectrum of CFTR gene mutations in Iranian Azeri Turkish patients with cystic
      fibrosis.
AB  - AIMS: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations
      in the CF transmembrane conductance regulator (CFTR) gene. In the present study,
      for the first time, we determined the spectrum of CFTR gene mutations in 100
      patients with CF originated from the Iranian Azeri Turkish ethnic group. RESULTS:
      Here, we report identification of 17 previously known and one novel mutation,
      namely K1302X, in this cohort. The frequency of deltaF508 mutation was found to
      be 23%. CONCLUSIONS: Low frequency of deltaF508 mutation and detection of one
      novel and 16 known mutations reflect a heterogeneous spectrum of the mutations in
      this ethnic group.

PMID- 21198396
TI  - Methylenetetrahydrofolate reductase polymorphisms C677T and A1298C as maternal
      risk factors for Down syndrome in Jordan.
AB  - BACKGROUND: The activity of the methylenetetrahydrofolate reductase (MTHFR)
      enzyme is regulated by the two polymorphisms C677T and A1298C, which reduce
      enzyme activity and result in hypomethylation of chromosomes that increase the
      risk of nondisjunction. These polymorphisms are suggested to be risk factors for
      Down syndrome (DS) in some populations. AIM: The aim of this study was to test if
      C677T and A1298C polymorphisms are correlated to maternal risk of DS in Jordan.
      METHODS: The proportions of C677T and A1298C polymorphisms were examined in 53
      case mothers who delivered DS children and 29 controls. The median age of case
      mothers was 35 years when delivering their affected children. Polymerase chain
      reaction-restriction fragment length polymorphism was used for genotyping.
      RESULTS: The frequency of MTHFR C677T allele in all DS mothers was 3.2-fold
      higher than in the controls (odds ratio [OR] = 3.12, 95% confidence interval
      [CI]: 1.303-7.677). Also, the proportion of 677T in the older case mothers was
      different from the controls, but was significantly higher in younger case mothers
      than in the controls (OR = 4.2, 95% CI: 1.61-10.97, p = 0.003). The proportions
      of 677CT and 677TT genotypes in younger cases are, respectively, 10- and 9-fold
      higher than in the controls. The proportions of MTHFR A1298C are significantly
      different among all case groups and the controls (chi(2) = 4.27, p = 0.127), but
      there was a significant difference between young case mothers and both older case
      mothers group and the controls (OR = 1.25, 95% CI: 0.405-3.85, p = 0.698).
      CONCLUSIONS: There is strong association between MTHFRC677T and maternal risk of
      DS in Jordanian mothers younger than 35 years old and the MTHFR1298C allele has a
      lesser but additive risk effect in MTHFR677T/1298C compound heterozygotes.

PMID- 21198399
TI  - Helper-dependent adenoviral vector achieves prolonged, stable expression of
      interleukin-10 in rabbit carotid arteries but does not limit early atherogenesis.
AB  - Vascular gene therapy could potentially complement or replace current therapies
      for human atherosclerosis, while avoiding their side effects. However,
      development of vascular gene therapy is limited by lack of a useful vector.
      Helper-dependent adenovirus (HDAd) shows promise to overcome this barrier
      because, unlike first-generation adenovirus, HDAd achieves durable transgene
      expression in the artery wall with minimal inflammation. To begin to test whether
      HDAd, delivered to the artery wall, can limit atherosclerosis we constructed HDAd
      that expresses rabbit interleukin (IL)-10, a potent atheroprotective cytokine,
      and tested its activity in a rabbit model of early carotid atherogenesis. HDAd
      expressed immunoreactive, active IL-10 in vitro. In contrast to other HDAd
      expressed transgenes, IL-10 expression from HDAd increased significantly between
      3 days and 2 weeks after infusion and remained stable for at least 8 weeks.
      Rising, persistent IL-10 expression was associated with relative persistence of
      HDAdIL-10 genomes 4 weeks after infusion, compared with HDAdNull genomes.
      Surprisingly, IL-10 expression had no significant effects on atherosclerotic
      lesion size, macrophage content, or expression of either adhesion molecules or
      atherogenic cytokines. These results might be due to inadequate protein
      expression in vivo or lack of suitability of this rabbit model to reveal IL-10
      therapeutic effects. IL-10 remains a promising agent for vascular gene therapy
      and HDAd remains a promising vector; however, proof of efficacy of HDAdIL-10 is
      elusive. Future preclinical studies will be aimed at increasing IL-10 expression
      levels and improving the sensitivity of this animal model to detect
      atheroprotective effects.

PMID- 21198400
TI  - Long-term maintenance of undifferentiated human embryonic and induced pluripotent
      stem cells in suspension.
AB  - Traditionally, undifferentiated pluripotent human embryonic and induced
      pluripotent stem cells (hESCs and hiPSCs) have been expanded as monolayer
      colonies in adhesion culture, both in the presence or absence of feeder cells.
      However, the use of pluripotent stem cells poses the need to scale-up current
      culture methods. Herein, we present the cultivation of 2 hESC lines (Royan H5 and
      Royan H6) and 2 hiPSC lines (hiPSC1 and hiPSC4) as carrier-free suspension
      aggregates for an extended period of time. The cells proliferated over multiple
      passages kept a stable karyotype, which successfully maintained an
      undifferentiated state and pluripotency, as determined by marker expressions in
      addition to in vitro spontaneous and directed differentiation. Additionally,
      these cells can be easily frozen and thawed without losing their proliferation,
      karyotype stability, and developmental potential. Transcriptome analysis of the 3
      lines revealed that the adherent culture condition was nearly identical to the
      suspension culture in Royan H5 and hiPSC1, but not in Royan H6. It remains
      unclear whether this observation at the transcript level is biologically
      significant. In comparison with recent reports, our study presents a low-cost
      procedure for long-term suspension expansion of hESCs and hiPSCs with the
      capability of freeze/thawing, karyotype stability, and pluripotency. Our results
      will pave the way for scaled up expansion and controlled differentiation of hESCs
      and hiPSCs needed for cell therapy, research, and industrial applications in a
      bioreactor culture system.

PMID- 21198398
TI  - Inhibition of p38 mitogen-activated protein kinase promotes ex vivo hematopoietic
      stem cell expansion.
AB  - Hematopoietic stem cell (HSC) self-renewal is tightly regulated by a complex
      crosstalk between many cell-intrinsic regulators and a variety of extrinsic
      signals from the stem cell niche. In this study, we examined whether the p38
      mitogen-activated protein kinase (p38) is one of the intrinsic regulators that
      can negatively regulate HSC self-renewal in vitro and whether inhibition of p38
      activity with a small molecule inhibitor can promote HSC expansion ex vivo. The
      results from this study showed that sorted mouse bone marrow Lin(-)Sca1(+)c
      kit(+) cells (LSK(+) cells) exhibited selective activation of p38 after culture
      in a serum-free medium supplemented with 100 ng/mL stem cell factor,
      thrombopoietin, and Flt3 ligand. The activation of p38 was associated with a
      significant reduction in HSCs and induction of apoptosis and cellular senescence
      in LSK(+) cells and their progeny. Addition of the specific p38 inhibitor
      SB203580 (SB, 5 MUM) to the culture inhibited the activation of p38 in LSK(+)
      cells, which led to increase in HSC self-renewal and ex vivo expansion as shown
      by the cobblestone area forming cell assay, competitive repopulation, and serial
      transplantation. The increase in HSC expansion is likely attributable to SB
      mediated inhibition of HSC apoptosis and senescence and upregulation of HoxB4 and
      CXCR4. These findings suggest that p38 plays an important role in the regulation
      of HSC self-renewal in vitro and inhibition of p38 activation with a small
      molecule inhibitor may represent a novel approach to promote ex vivo expansion of
      HSCs.

PMID- 21198401
TI  - Special issue "scoliosis and evidence based practice".

PMID- 21198402
TI  - Scoliosis and evidence-based practice.

PMID- 21198403
TI  - Patient evaluation in idiopathic scoliosis: Radiographic assessment, trunk
      deformity and back asymmetry.
AB  - Progressive adolescent idiopathic scoliosis (AIS) produces specific signs and
      symptoms, including trunk and spinal deformity and imbalance, impairment of
      breathing function, pain, progression during adult life, and psychological
      problems, as a whole resulting in an alteration of the health-related quality of
      life. A scoliosis-specific rehabilitation program attempts to prevent, improve,
      or minimize these signs and symptoms by using exercises and braces as the main
      tools in the rehabilitation treatment. Patient evaluation is an essential point
      in the decision-making process and determines the selection of the specific
      exercises and the specifications of the brace design. However, this article is
      not addressed to scoliosis management. In this present article, a complete
      definition and discussion of radiological aspects, such as the Cobb angle, axial
      rotation, curve pattern classifications, and sagittal configuration, follow a
      short description of the three-dimensional nature of AIS. The relationship
      between AIS and growth is also discussed. There is also a section dedicated to
      the assessment of trunk deformity and back asymmetry. Other important clinical
      aspects, such as pain and disability, changes in other regions of the body,
      muscular balance, breathing function, and health-related quality of life, are not
      discussed in this present article.

PMID- 21198404
TI  - Effectiveness and outcomes of brace treatment: a systematic review.
AB  - Bracing has been widely used for the treatment of adolescent idiopathic scoliosis
      (AIS). However, effectiveness of brace treatment remains controversial. A
      systematic review was conducted to investigate evidence that brace treatment is
      effective in the treatment of AIS. A total of 20 studies, including randomized
      controlled trials, nonrandomized clinical controlled trials, or case-control
      studies, were included. Studies comparing the results of brace treatment with no
      treatment, other conservative treatments, or surgical treatment were included.
      Outcomes of the studies included radiological curve progression, incidence of
      surgery, pulmonary function, quality of life (QOL), and psychological state. The
      results from the systematic review are difficult to interpret. There are quite a
      number of varying parameters between studies that make it very difficult to reach
      any firm conclusions. In addition, the quality of evidence is limited because
      most of the studies included in this review were of low methodological quality.
      However, the available data suggest that, compared to observation, bracing is
      more potent in preventing the progression of scoliosis and may not have a
      negative impact on patients' QOL. Therefore, bracing can be recommended for the
      treatment of AIS, at least for female patients with a Cobb angle of 25-35 degrees
      . Compared to other conservative treatments, bracing seems to be more effective
      than electrical stimulation, although an advantage of bracing over side-shift
      exercise or casting has not been established. Comparison between bracing and
      surgery is difficult because in most studies, the curve magnitude at baseline was
      considerably larger in the surgery group. We recommend that future studies have
      clearer and more consistent guidelines.

PMID- 21198405
TI  - The SPoRT concept of bracing for idiopathic scoliosis.
AB  - The SPoRT (acronym: Symmetrical, Patient-oriented, Rigid, Three-dimensional,
      active) concept of bracing is a new way to build braces based on our 20 years of
      experience and the biomechanical principles of scoliosis correction, inclusive of
      the Sibilla and Sforzesco braces. The concept always requires a custom brace,
      which is made according to the patient's individual requirements. New
      technologies such as CAD-CAM can be applied, and often for better results,
      without the customary use of prebuilt forms whose measurements are stored in
      databases. Once the initial draft brace is completed, a final test must be made
      on the patient to modify and adapt it, depending on his or her real interaction
      between the body and the brace. The results that are today available on the SPoRT
      concept relate to the Sforzesco brace and are necessarily short-term, because the
      first treated patients are now reaching the fourth-year follow-up examination and
      haven't yet completed their treatments. On the basis of the initial evaluations,
      we can state that the Sforzesco brace is more effective than the Lyon brace after
      6 months of treatment and that the Sforzesco brace is equally effective as the
      Risser Plast brace.

PMID- 21198406
TI  - Expert-driven Cheneau applications: Description and in-brace corrections.
AB  - In-brace correction and compliance are the main predictors of a successful
      outcome of brace treatment in the management of patients with idiopathic
      scoliosis. The latest CAD/CAM- or module-based bracing concepts related to a
      proper classification have led to better in-brace corrections and have made the
      braces easier to wear for the patient. However, even the latest developments on
      the market do not ensure successful treatment in every case. Thoracic curves with
      Cobb angles less than 50 degrees  may be treated with the best likelihood of
      success utilizing the latest Cheneau derivates, enabling a real 3D correction
      that includes sagittal correction of the spine, when patient compliance can be
      achieved. The successful application of the braces demands a proper
      classification of curve patterns. The percentage of in-brace correction of the
      Cobb angle correlates with the end result and consequently is a good indicator
      for brace quality. However, other factors, such as 3D correction or the absolute
      reduction of the Cobb angle (i.e., in rigid curves over 50 degrees ), might also
      be important indicators.

PMID- 21198407
TI  - Physical exercises in the treatment of adolescent idiopathic scoliosis: an
      updated systematic review.
AB  - Two years ago we published an update of another of our previous systematic
      reviews about the effectiveness of physical exercises (PEs), and we found that
      the evidence on exercises for AIS was of level 1b. Now we have updated these
      results in the field of exercises for AIS with the final aim to find the
      strongest evidence as possible about PEs. Our goal was to verify if treatment
      with specific exercises for AIS has changed in these years. The study design was
      a systematic review. A bibliographic search with strict inclusion criteria
      (patients treated exclusively with exercises, outcome Cobb degrees, all study
      designs) has been performed on the main electronic databases. We found a new
      paper about active autocorrection (Negrini et al, 2008 b), a prospective
      controlled cohort observational study on patients never treated before so the
      number of manuscripts considered in the systematic review was 20. The highest
      quality study (RCT) compared 2 groups of 40 patients, showing an improvement of
      the curve in all treated patients after 6 months. All studies confirmed the
      efficacy of exercises in reducing the progression rate (mainly in early puberty)
      and/or improving the Cobb angles (around the end of growth). Exercises were also
      shown to be effective in reducing brace prescription. Appendices of the popular
      exercise protocols that have been used in the research studies that are examined
      are included with detailed description and illustrations. This study (like the
      previously published systematic reviews) showed that PEs can improve the Cobb
      angles of individuals with AIS and can improve strength, mobility, and balance.
      The level of evidence remains 1b according to the Oxford Centre for Evidence
      based Medicine, as previously documented.

PMID- 21198409
TI  - Short communication decreased incidence of dual infections in South african
      subtype C-infected women compared to a cohort ten years earlier.
AB  - Previously, we determined the incidence of dual infections in a South African
      cohort and its association with higher viral setpoint. Ten years later, we
      compare the incidence and impact of dual infections at transmission on viral
      setpoint in a geographically similar cohort (n = 46) making use of both the
      heteroduplex mobility assay (HMA) and the more recent single genome amplification
      (SGA) approach. HIV incidence was lower in this cohort (7% compared to 18%), and
      we find a similar reduction in the number of dual infections (9% compared to
      19%). Unlike the previous study, there was no association between either dual
      infection (n = 4) or multivariant transmission (n = 7) and disease progression.
      This study emphasized the importance of monitoring changes in the HIV epidemic as
      it may have important ramifications on our understanding of the natural history
      of disease.

PMID- 21198410
TI  - Encapsulating contact allergens in liposomes, ethosomes, and polycaprolactone may
      affect their sensitizing properties.
AB  - Attempts to improve formulation of topical products are a continuing process and
      the development of micro- and nanovesicular systems as well as polymeric
      microparticles has led to marketing of topical drugs and cosmetics using these
      technologies. Encapsulation of some well-known contact allergens in ethanolic
      liposomes have been reported to enhance allergenicity compared with the allergens
      in similar vehicles without liposomes. The present report includes data on more
      sensitization studies using the mouse local lymph node assay with three contact
      allergens encapsulated in different dermal drug-delivery systems: liposomes,
      ethosomes, and polycaprolactone particles. The results show that the drug
      delivery systems are not sensitizers in themselves. Encapsulating the hydrophilic
      contact allergen potassium dichromate in all three drug-delivery systems did not
      affect the sensitizing capacity of potassium dichromate compared with control
      solutions. However, encapsulating the lipophilic contact allergen
      dinitrochlorobenzene (DNCB) in polycaprolactone reduced the sensitizing capacity
      to 1211 +/- 449 compared with liposomes (7602 +/- 2658) and in acetone:olive oil
      (4:1) (5633 +/- 666). The same trend was observed for encapsulating isoeugenol in
      polycaprolactone (1100 +/- 406) compared with a formulation in acetone:olive oil
      (4491 +/- 819) and in liposomes (3668 +/- 950). Further, the size of DNCB-loaded
      liposomes did not affect the sensitizing properties. These results suggest that
      modern dermal drug-delivery systems may in some cases magnify or decrease the
      sensitizing capacity of the encapsulated contact allergen.

PMID- 21198412
TI  - Cognitive functioning in elderly women who underwent unilateral oophorectomy
      before menopause.
AB  - The objective of this study is to compare differences in the cognitive
      functioning of elderly women who underwent unilateral oophorectomy before
      menopause with women who passed through natural menopause. A case-control study
      was conducted from December 2009 to August 2010. We studied the cognitive
      functioning of 50 elderly women who had undergone unilateral oophorectomy alone
      (20 cases) or with abdominal hysterectomy (30 cases) before menopause for a
      benign indication between May 1985 and December 1989. Tests of cognitive
      functioning were compared with results from 50 demographically matched control
      women. Test results for the unilateral oophorectomy group were lower than the
      control group, as measured on three separate trials for immediate and delayed
      word recall (p < .05). Hence we can conclude unilateral oophorectomy before
      menopause may have long-term deleterious effects on cognitive functioning in
      elderly women.

PMID- 21198411
TI  - Molecular epidemiological analysis of paired pol/env sequences from Portuguese
      HIV type 1 patients.
AB  - The advent of new therapeutic approaches targeting env and the search for
      efficient anti-HIV-1 vaccines make it necessary to identify the number of
      recombinant forms using genomic regions that were previously not frequently
      sequenced. In this study, we have subtyped paired pol and env sequences from HIV
      1 strains infecting 152 patients being clinically followed in Portugal. The
      percentage of strains in which we found discordant subtypes in pol and env was
      25.7%. When the subtype in pol and env was concordant (65.1%), the most prevalent
      subtypes were subtype B (40.8%), followed by subtype C (17.8%) and subtype G
      (5.3%). The most prevalent recombinant form was CRF14_BGpol/Genv (7.2%).

PMID- 21198414
TI  - Young-onset parkinsonism in a Hong Kong Chinese man with adult-onset Hallervorden
      Spatz syndrome.
AB  - Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group of
      disorders varied in genetic etiologies, clinical presentations, and radiological
      features. NBIA is an iron homeostasis disorder with progressive iron accumulation
      in the central nervous systems and is clinically characterized by extrapyramidal
      movement abnormalities, retinal pigmentary changes, and cognitive impairment.
      Panthothenate kinase-associated neurodegeneration (Hallervorden-Spatz disease) is
      the commonest disorder of NBIA with a prevalence of one-three per million.
      Clinically, it is classified into early-onset childhood, atypical late-onset, and
      adult-onset type. Adult-onset type is rarer. We report the first case of adult
      onset panthothenate kinase-associated neurodegeneration in Hong Kong in a 28-year
      old Chinese man who presented with pure young-onset parkinsonism. Magnetic
      resonance imaging (MRI) of the brain showed the presence of eye-of-the-tiger
      sign. Two compound heterozygous mutations PANK2 NM_153638.2: c.445G > T;
      NP_705902.2: p.E149X and PANK2 NM_153638.2: c.1133A > G; NP_705902.2: p.D378G
      were detected. Parkinsonism per se is a very heterogeneous phenotypic group. In
      view of the readily available genetic analysis of PANK2, panthothenate kinase
      associated neurodegeneration should be considered in adult patients with young
      onset parkinsonism with or without the eye-of-the-tiger sign. The exact diagnosis
      offers a different management approach and genetic counseling. NBIA is likely
      under- or misdiagnosed in Hong Kong Chinese.

PMID- 21198416
TI  - NTCP modelling of lung toxicity after SBRT comparing the universal survival curve
      and the linear quadratic model for fractionation correction.
AB  - BACKGROUND: In SBRT of lung tumours no established relationship between dose
      volume parameters and the incidence of lung toxicity is found. The aim of this
      study is to compare the LQ model and the universal survival curve (USC) to
      calculate biologically equivalent doses in SBRT to see if this will improve
      knowledge on this relationship. MATERIAL AND METHODS: Toxicity data on radiation
      pneumonitis grade 2 or more (RP2+) from 57 patients were used, 10.5% were
      diagnosed with RP2+. The lung DVHs were corrected for fractionation (LQ and USC)
      and analysed with the Lyman- Kutcher-Burman (LKB) model. In the LQ-correction
      alpha/beta = 3 Gy was used and the USC parameters used were: alpha/beta = 3 Gy,
      D(0) = 1.0 Gy, [Formula: see text] = 10, alpha = 0.206 Gy(-1) and d(T) = 5.8 Gy.
      In order to understand the relative contribution of different dose levels to the
      calculated NTCP the concept of fractional NTCP was used. This might give an
      insight to the questions of whether "high doses to small volumes" or "low doses
      to large volumes" are most important for lung toxicity. RESULTS AND DISCUSSION:
      NTCP analysis with the LKB-model using parameters m = 0.4, D(50) = 30 Gy resulted
      for the volume dependence parameter (n) with LQ correction n = 0.87 and with USC
      correction n = 0.71. Using parameters m = 0.3, D(50) = 20 Gy n = 0.93 with LQ
      correction and n = 0.83 with USC correction. In SBRT of lung tumours, NTCP
      modelling of lung toxicity comparing models (LQ,USC) for fractionation
      correction, shows that low dose contribute less and high dose more to the NTCP
      when using the USC-model. Comparing NTCP modelling of SBRT data and data from
      breast cancer, lung cancer and whole lung irradiation implies that the response
      of the lung is treatment specific. More data are however needed in order to have
      a more reliable modelling.

PMID- 21198417
TI  - Increase in motor neuron disease mortality in Spain: temporal and geographical
      analysis (1990-2005).
AB  - The aim of this study was to assess the trend of motor neuron disease mortality
      in Spain from 1990 to 2005, and to ascertain the existence of geographical
      differences in mortality rates. MND deaths are registered by the National
      Statistics Institute of Spain - International Classification of Diseases (ICD)
      codes ICD9 335.2 (1990-1998) and ICD10 G12.2 (1999-2005). Annual sex- and age
      specific rates, as well as rates adjusted for the standard European population
      were obtained. Provincial standardized mortality ratios (SMRs) were calculated
      for the study period. Respective provincial SMRs were smoothed with data from
      adjacent provinces using a Poisson model. Results showed that MND mortality
      increased in Spain from 1990 to 2005. Geographical differences between provinces
      were evident throughout the study period. In general, risk of death due to MND
      was higher in regions lying to the north of Spain. In conclusion, the temporal
      and geographical variability observed might be explained by genetic factors,
      differences in environmental exposures and the possible influence of the type of
      medical care and treatment received. Mortality depends also on health service
      quality and diagnostic validity. All these factors may play a very important role
      in analysis of MND mortality in Spain, and the contribution of each of these will
      have to be examined in depth by ad hoc studies.

PMID- 21198413
TI  - Sustained delivery of dibutyryl cyclic adenosine monophosphate to the transected
      spinal cord via oligo [(polyethylene glycol) fumarate] hydrogels.
AB  - This study describes the use of oligo [(polyethylene glycol) fumarate] (OPF)
      hydrogel scaffolds as vehicles for sustained delivery of dibutyryl cyclic
      adenosine monophosphate (dbcAMP) to the transected spinal cord. dbcAMP was
      encapsulated in poly(lactic-co-glycolic acid) (PLGA) microspheres, which were
      embedded within the scaffolds architecture. Functionality of the released dbcAMP
      was assessed using neurite outgrowth assays in PC12 cells and by delivery to the
      transected spinal cord within OPF seven channel scaffolds, which had been loaded
      with Schwann cells or mesenchymal stem cells (MSCs). Our results showed that
      encapsulation of dbcAMP in microspheres lead to prolonged release and continued
      functionality in vitro. These microspheres were then successfully incorporated
      into OPF scaffolds and implanted in the transected thoracic spinal cord.
      Sustained delivery of dbcAMP inhibited axonal regeneration in the presence of
      Schwann cells but rescued MSC-induced inhibition of axonal regeneration. dbcAMP
      was also shown to reduce capillary formation in the presence of MSCs, which was
      coupled with significant functional improvements. Our findings demonstrate the
      feasibility of incorporating PLGA microsphere technology for spinal cord
      transection studies. It represents a novel sustained delivery mechanism within
      the transected spinal cord and provides a platform for potential delivery of
      other therapeutic agents.

PMID- 21198418
TI  - Neurofilament heavy subunit in cerebrospinal fluid: a biomarker of amyotrophic
      lateral sclerosis?
AB  - The objectives of this study were to investigate the presence of the three
      neurofilament subunits, ubiquitin, proteasome and 3-nitrotyrosine, in CSF samples
      of ALS patients. CSF samples were obtained by lumbar puncture from 10 ALS
      patients and six controls. All samples were analysed by Western blotting. Results
      revealed that neurofilament heavy subunit was identified in 70% of ALS cases and
      we conclude that this subunit may be a promising biomarker for clinical diagnosis
      of ALS.

PMID- 21198419
TI  - Multimodal psychodynamic psychotherapy induces normalization of reward related
      activity in somatoform disorder.
AB  - OBJECTIVES: Somatoform disorder patients demonstrate a disturbance in the balance
      between internal and external information processing, with a decreased focus on
      external stimulus processing. We investigated brain activity of somatoform
      disorder patients, during the processing of rewarding external events, paying
      particular attention to the effects of inpatient multimodal psychodynamic
      psychotherapy. METHODS: Using fMRI, we applied a reward task that required fast
      reactions to a target stimulus in order to obtain monetary rewards; a control
      condition contained responses without the opportunity to gain rewards. Twenty
      acute somatoform disorder patients were compared with twenty age-matched healthy
      controls. In addition, 15 patients underwent a second scanning session after
      participation in multimodal psychodynamic psychotherapy. RESULTS: Acute patients
      showed diminished hemodynamic differentiation between rewarding and non rewarding
      events in four regions, including the left postcentral gyrus and the right
      ventroposterior thalamus. After multimodal psychodynamic psychotherapy, both
      regions showed a significant normalization of neuronal differentiation.
      CONCLUSION: Our results suggest that diminished responsiveness of brain regions
      involved in the processing of external stimuli underlies the disturbed balance of
      internal and external processing of somatoform disorder patients. By providing
      new approaches to cope with distressing events, multimodal psychodynamic
      psychotherapy led to decreased symptoms and normalization of neuronal activity.

PMID- 21198420
TI  - Epigenetics in the unicellular parasite Entamoeba histolytica.
AB  - Amoebiasis is a serious infectious disease that is caused by the unicellular
      parasite, Entamoeba histolytica. This parasite is mainly found in developing
      countries, and are named owing to its ability to destroy tissues. The molecular
      mechanisms that regulate the virulence of this parasite are not well understood.
      In recent years, an increasing interest in the epigenetic regulation of the
      parasite's virulence has emerged. In this article, an overview of our current
      knowledge about the role of DNA methylation, histone modifications and RNA
      associated silencing in the biology of E. histolytica is provided. The relevance
      of some features of the parasite's unique epigenetic machinery to the development
      of new antiamoebic therapeutic molecules is discussed.

PMID- 21198421
TI  - Comparison of hyperbaric oxygen and medical ozone therapies in a rat model of
      experimental distal colitis.
AB  - OBJECTIVES: Previous studies have shown that hyperbaric oxygen (HBO) is effective
      in reducing the severity of acute distal colitis (ADC). Ozone therapy (OT)
      reduces inflammation in several pathological conditions. We aimed to compare the
      effects of HBO therapy and OT in an experimental ADC rat model. MATERIALS AND
      METHODS: Forty rats were randomly divided into four groups: Sham, ADC, ADC + HBO,
      and ADC + OT. Rats in the sham group were given isotonic saline. In the remaining
      groups, ADC was created by intracolonic administration of 4% acetic acid. No
      treatment was given to the ADC group. The rats in the ADC + HBO and ADC + OT
      groups were given HBO and ozone treatments, respectively. The administration of
      acetic acid caused an inflammatory response in all animals. Distal colons and
      blood samples were obtained. RESULTS: The histopathological score was
      significantly higher in the ADC group compared to the other groups. The
      histopathological scores in the ADC + HBO and ADC + OT groups were significantly
      lower compared to the ADC group (both p < 0.001). The most pronounced therapeutic
      effect was observed in the ADC + OT group. Malondialdehyde and neopterin levels
      and superoxide dismutase and glutathione peroxidase activities in the ADC group
      were significantly higher compared to the other groups (p < 0.001). CONCLUSION:
      Our data showed that the therapeutic effect of OT is more pronounced than that of
      HBO therapy. Its possible effect is by means of decreasing inflammation, edema,
      and oxidative stress. These findings also suggest that it is possible to improve
      the outcome of ADC by using ozone therapy as an adjuvant therapy.

PMID- 21198423
TI  - Individualized higher dose of 70-75 Gy using five-fraction robotic stereotactic
      radiotherapy for non-small-cell lung cancer: a feasibility study.
AB  - OBJECTIVE: To determine whether robotic stereotactic radiotherapy of 70-75 Gy
      delivered in five fractions results in an improved therapeutic ratio, compared
      with three fractions, in the treatment of peripheral non-small-cell lung cancer
      (NSCLC), in which case doses of up to 85 Gy in five fractions may be feasible.
      MATERIALS AND METHODS: Between December 2006 and May 2010, 20 patients (9 female,
      11 male, aged 65 to 88) were treated using the CyberKnife(r) Robotic Radiosurgery
      System for NSCLC with doses ranging from 67 Gy to 75 Gy based on location,
      histopathological type, grade of histopathological differentiation, tumor
      diameter/volume, and normal tissue constraints, with the doses being delivered in
      five fractions over 5 to 8 days. Tumor diameters ranged from 1.5 cm to 3.4 cm
      (median: 2.5 cm). Patients with Stage I to IV NSCLC were treated, and the results
      and observations were analyzed for clinical characteristics and outcomes
      including toxicity. All patients, except one who had refused surgery, had co
      morbid conditions that precluded a lobectomy. RESULTS: Twenty patients were
      followed every three months by positron emission tomography/computed tomography
      (PET/CT). Mean follow-up was 23 months (range: four to 58 months). Local control
      was achieved in all treated tumors. Three patients expired, and three developed
      new regional metastases, none of which was within the planning target volume
      (PTV). The remainder of the patients demonstrated no evidence of recurrence or
      continued growth detectable by PET/CT. There was no toxicity above Grade 1.
      CONCLUSIONS: It is feasible to treat peripheral NSCLC with individualized maximal
      tolerable doses ranging from 67 Gy to 75 Gy in five fractions chosen on the basis
      of location, histopathological type, grade of histopathological differentiation,
      tumor diameter/volume, and normal tissue constraints.

PMID- 21198422
TI  - Cystatin C, a marker for successful aging and glomerular filtration rate, is not
      influenced by inflammation.
AB  - BACKGROUND: The plasma level of cystatin C is a better marker than plasma
      creatinine for successful aging. It has been assumed that the advantage of
      cystatin C is not only due to it being a better marker for glomerular filtration
      rate (GFR) than creatinine, but also because an inflammatory state of a patient
      induces a raised cystatin C level. However, the observations of an association
      between cystatin C level and inflammation stem from large cohort studies. The
      present work concerns the cystatin C levels and degree of inflammation in
      longitudinal studies of individual subjects without inflammation, who undergo
      elective surgery. METHODS: Cystatin C, creatinine, and the inflammatory markers
      CRP, serum amyloid A (SAA), haptoglobin and orosomucoid were measured in plasma
      samples from 35 patients the day before elective surgery and subsequently during
      seven consecutive days. RESULTS: Twenty patients had CRP-levels below 1 mg/L
      before surgery and low levels of the additional inflammatory markers. Surgery
      caused marked inflammation with high peak values of CRP and SAA on the second day
      after the operation. The cystatin C level did not change significantly during the
      observation period and did not correlate significantly with the level of any of
      the four inflammatory markers. The creatinine level was significantly reduced on
      the first postoperative day but reached the preoperative level towards the end of
      the observation period. CONCLUSION: The inflammatory status of a patient does not
      influence the role of cystatin C as a marker of successful aging, nor of GFR.

PMID- 21198424
TI  - Development of a femoral template for computer-assisted tunnel placement in
      anatomical double-bundle ACL reconstruction.
AB  - Femoral graft placement is an important factor in the success of anterior
      cruciate ligament (ACL) reconstruction. In addition to improving the accuracy of
      femoral tunnel placement, Computer Assisted Surgery (CAS) can be used to
      determine the anatomic location. This is achieved by using a 3D femoral template
      which indicates the position of the anatomical ACL center based on endoscopically
      measurable landmarks. This study describes the development and application of
      this method. The template is generated through statistical shape analysis of the
      ACL insertion, with respect to the anteromedial (AM) and posterolateral (PL)
      bundles. The ligament insertion data, together with the osteocartilage edge on
      the lateral notch, were mapped onto a cylinder fitted to the intercondylar notch
      surface (n = 33). Anatomic variation, in terms of standard variation of the
      positions of the ligament centers in the template, was within 2.2 mm. The
      resulting template was programmed in a computer-assisted navigation system for
      ACL replacement and its accuracy and precision were determined on 31 femora. It
      was found that with the navigation system the AM and PL tunnels could be
      positioned with an accuracy of 2.5 mm relative to the anatomic insertion centers;
      the precision was 2.4 mm. This system consists of a template that can easily be
      implemented in 3D computer navigation software. Requiring no preoperative images
      and planning, the system provides adequate accuracy and precision to position the
      entrance of the femoral tunnels for anatomical single- or double-bundle ACL
      reconstruction.

PMID- 21198425
TI  - Evaluation of a fluoroscopy-based navigation system enabling a virtual radiation
      free preview of X-ray images for placement of cannulated hip screws. A cadaver
      study.
AB  - Accurate placement of cannulated screws is essential to ensure fixation of medial
      femoral neck fractures. The conventional technique may require multiple guide
      wire passes, and relies heavily on fluoroscopy. A computer-assisted planning and
      navigation system based on 2D fluoroscopy for guide wire placement in the femoral
      neck has been developed to improve screw placement. The planning process was
      supported by a tool that enables a virtual radiation-free preview of X-ray
      images. This is called "zero-dose C-arm navigation". For the evaluation of the
      system, six formalin-fixed cadaveric full-body specimens (12 femurs) were used.
      The evaluation demonstrated the feasibility of fluoroscopically navigated guide
      wire and implant placement. Use of the novel system resulted in a significant
      reduction in the number of fluoroscopic images and drilling attempts while
      achieving optimized accuracy by attaining better screw parallelism and enlarged
      neck-width coverage. Operation time was significantly longer in the navigation
      assisted group. The system has yielded promising initial results; however,
      additional studies using fractured bone models and with extension of the
      navigation process to track two bone fragments must be performed before
      integration of this navigation system into the clinical workflow is possible, and
      these studies should focus on reducing the operation time.

PMID- 21198426
TI  - Robotics in urological surgery: review of current status and maneuverability, and
      comparison of robot-assisted and traditional laparoscopy.
AB  - To assess the current state of robot-assisted urological surgery, the literature
      concerning surgical robotic systems, surgical telemanipulators and laparoscopic
      systems was reviewed. Aspects of these systems pertaining to maneuverability were
      evaluated, with a view to quantifying their stability and locomotive properties
      and thereby determining their suitability for use in assisted laparoscopic
      procedures, particularly robot-assisted laparoscopic urological surgery. The
      degree of maneuverability and versatility of a robotic system determine its
      utility in the operating room, and the newer-generation surgical robotic systems
      have been found to possess a higher degree of maneuverability than older class 1
      and class 2 systems. It is now clearly established that robots have an important
      place in the urologist's armamentarium for minimally invasive surgery; however,
      the long-term outcomes of several urological procedures (other than robot
      assisted radical prostatectomy) performed with the da Vinci surgical robotic
      system have yet to be evaluated.

PMID- 21198427
TI  - HIV infection induces morphometrical changes on the oral (buccal mucosa and
      tongue) epithelial cells.
AB  - The aim of this study was to assess morphological and morphometrical alterations
      of oral squamous epithelial cells in type 1 HIV infected individuals. Oral smears
      were collected from tongue and buccal mucosa of 30 HIV infected (experimental)
      and 30 non-infected (control) individuals by liquid-based exfoliative cytology.
      The cells were morphologically analyzed and the nuclear area (NA), the
      cytoplasmic area (CA) and the nucleus-to-cytoplasm area ratio (NA/CA) were
      calculated. No morphological differences were found between the groups. The mean
      values of CA were decreased in tongue (P=.00006) and buccal mucosa (P=.00242) in
      HIV infected individual, while mean values of NA were increased (P=.00308 and
      .00095, respectively) in the same group. NA/CA ratio for experimental group was
      increased in both collected places, with P=.00001 (tongue) and P=.00000 (buccal
      mucosa). This study revealed that HIV infection was able to induce morphometrical
      changes on the oral epithelial cells.

PMID- 21198428
TI  - A RhoA-derived peptide inhibits human immunodeficiency virus-1 entry in vitro.
AB  - RhoA-derived peptides have been shown to have antiviral activity against both
      human respiratory syncytial virus and human parainfluenza virus-3. The present
      study investigates the toxicity, anti-HIV-1 activity and mechanism of action of a
      RhoA-derived peptide (RhoA 77-95). The efficacy of this peptide was compared to a
      scrambled peptide of the same amino acid composition and Enfuvirtide, a HIV entry
      inhibitor. Our data show that this RhoA-derived peptide is a non-toxic and
      effective inhibitor of a CXCR4 tropic strain of HIV-1. We also demonstrate that
      the mechanism of entry inhibition is likely mediated by polyanionic properties
      and is dependent on the dimerization of peptides.

PMID- 21198429
TI  - Cryptogenic liver diseases: sailing by sight from HIV co-infection with hepatitis
      viruses to HIV mono-infection through the Pillars of Hercules.
AB  - Liver injury in the HIV-positive population has been classically associated with
      hepatitis B or C viruses (HBV and HCV). While HBV or HCV co-infections have
      represented "Pillars of Hercules" for hepatic disease (not further beyond), it is
      now time to move forward and shed light on liver disease in HIV-infected patients
      without HBV or HCV co-infections. Indeed, over the last years, liver disease in
      HIV-mono-infected patients has emerged and fated to become one of the main non
      AIDS-related complications. Although several cases have specific etiologies
      (e.g., alcohol abuse), other cases are most challenging for the clinicians
      because the actual causes are only hypothesized, such as it is difficult to treat
      them appropriately. This new clinical entity has been named "cryptogenic" liver
      disease; it is polymorphic (e.g., hepatic steatosis, nodular regenerative
      hyperplasia or noncirrhotic portal hypertension) and multifactorial in nature,
      but HIV per se may play a key role. In this paper, we present a critical review
      of the relevant literature data, focusing on practical implications (including
      diagnostic tools and differential diagnosis), and delineate priorities for future
      research on this important topic.

PMID- 21198430
TI  - Late and low compliance with hepatitis B serology screening among HIV-infected
      patients in a resource-limited setting: an issue to improve HIV care.
AB  - Although hepatitis B serology screening has been recommended for HIV care, it has
      not been routinely performed. We aimed to assess compliance and timing of
      hepatitis B serology screening among HIV-infected patients in a resource-limited
      setting. A cross-sectional study was conducted in Thailand. Compliance, timing of
      hepatitis B serology screening, and factors associated with no HBsAg screening
      were determined. A total of 416 HIV-infected patients with 61% males were
      enrolled. Median (range) age at HIV diagnosis was 34 (16-75) years and 92% had
      heterosexual risk. Proportion of HBsAg screening and prevalence of positive HBsAg
      were 69.2% and 9.0%, respectively. There was no difference in the proportion of
      no HBsAg screening during the period 1990-2008 (p = 0.865). Proportion of anti
      HBs and anti-HBc screening were 40.9% and 21.2%, respectively. HBsAg was screened
      before or on the day of anti-HIV testing in 9.1% and before antiretroviral
      therapy (ART) initiation in 27.2%. By Kaplan-Meier analysis, median time from
      anti-HIV testing to HBsAg screening was 55.9 (95% confidence interval [CI] 43.9,
      68.3) months. By multivariate logistic regression, duration of HIV infection
      (odds ratio [OR] 1.14; 95% CI 1.07, 1.21), no anti-HBs screening (OR 1.65; 95% CI
      1.4-2.63), and no anti-HCV screening (OR 2.60; 95% CI 1.62, 4.17) were associated
      with no HBsAg screening before ART initiation. In conclusion, compliance with
      hepatitis B serology screening was relatively low and late. Educational program
      regarding hepatitis B serology screening, identification of barriers, and
      interventions to eliminate these barriers in resource-limited settings are
      crucial to improve HIV care.

PMID- 21198431
TI  - Fat tissue distribution changes in HIV-infected patients treated with
      lopinavir/ritonavir. Results of the MONARK trial.
AB  - Given the decline in mortality among HIV-infected patients, it has become
      increasingly important to consider delayed disease-related and/or anti-HIV
      therapy-related adverse effects, such as lipodystrophy, when choosing initial
      therapy. Data from the MONARK trial allowed for comparison of the potential
      lipodystrophic effects of lopinavir/ritonavir (LPV/r) monotherapy with those of
      triple therapy with LPV/r plus zidovudine (ZDV) and lamivudine (3TC). This was a
      randomized, open-label, multinational study that included 136 antiretroviral
      naive HIV-infected patients. A portion of study patients underwent evaluations of
      limb and trunk fat tissue by dual-energy x-ray absorptiometry at baseline and
      after 48 weeks of treatment (and 96 weeks in some patients). Sixty-three patients
      had paired absorptiometry data at baseline and week 48 (13 patients at week 96).
      At week 48, median change in limb fat was -63 g on LPV/r monotherapy versus -703
      g on LPV/r + ZDV/3TC triple therapy (p=0.014). The proportion of patients with
      fat loss (>20% loss in limb fat) was significantly lower with LPV/r monotherapy
      (4.9% versus 27.3%; p=0.018). Changes in trunk fat did not differ significantly
      between treatments. Nonetheless, limb fat and trunk fat varied in the same
      direction with both treatments. The decrease in arm lean mass was also
      significantly less in patients receiving LPV/r monotherapy. Only treatment type
      emerged as a significant predictor of fat loss (odds ratio, 7.06; 95% CI, 1.11
      78.69). These results suggest that LPV/r, and possibly other protease inhibitors,
      may not be the main contributor to lipoatrophy in HIV-infected patients receiving
      triple therapy.

PMID- 21198432
TI  - Long-term safety from the raltegravir clinical development program.
AB  - BACKGROUND: Raltegravir has demonstrated potent and durable efficacy and a
      favorable safety profile in 3 phase III studies in treatment-naive and treatment
      experienced patients with HIV-1 infection. This manuscript provides a review of
      the raltegravir safety profile using data from these and other studies in the
      clinical development program. METHODS: Comprehensive 96-week safety data from
      STARTMRK (raltegravir versus efavirenz, each with tenofovir/emtricitabine) and
      BENCHMRK (raltegravir versus placebo, each with optimized background therapy) are
      summarized. A cumulative meta-analysis of raltegravir 400 mg bid was conducted
      across the entire development program. RESULTS: In STARTMRK, drug-related adverse
      events (AEs) occurred less frequently with raltegravir than efavirenz. In
      BENCHMRK, the most common drug-related AEs occurred at generally similar
      frequencies in both groups. Drug-related serious AEs were uncommon. Rash was
      observed in raltegravir-treated patients at a higher frequency than placebo but a
      lower frequency than efavirenz. Depression and immune reconstitution inflammatory
      syndrome occurred at similar rates for raltegravir and comparators. Isolated
      elevations of creatine kinase were more common with raltegravir than placebo but
      occurred without clinical manifestations. The frequency of aminotransferase
      elevations was greater in patients with viral hepatitis co-infection, but similar
      in the raltegravir and comparator groups. The relative risk (95% CI) of cancer
      was 0.75 (0.30, 1.91) indicating no difference between raltegravir and
      comparator. Overall trends in the cumulative meta-analysis were similar to those
      observed in the phase III studies. CONCLUSIONS: Long-term data from the phase III
      clinical trials demonstrate that raltegravir was generally well-tolerated in both
      treatment-naive and treatment-experienced patients with HIV infection.

PMID- 21198433
TI  - High mobility group box protein-1 in HIV-1 infection.
AB  - Chronic immune activation driven by microbial translocation from a damaged gut
      plays a fundamental role in HIV-1 progression. However, the exact link between a
      leaky gut and immune activation remains to be established. A growing body of
      evidence suggests that high mobility group box protein-1 (HMGB1) may be involved
      in this process. HMGB1 is a DNA binding protein present in every nucleated cell,
      which might be actively secreted to the extracellular milieu by activated cells
      or passively released from damaged or dying cells. The biological effect depends
      on its ability to form complexes: HMGB1 alone signals through the receptor of
      advanced glycosylated end products (RAGE) and promotes regeneration and repair,
      whereas HMGB1 in complex with bacterial products signal via toll like receptors
      (TLRs) and promotes immune activation. Plasma levels of HMGB1 are elevated in HIV
      1 infected patients and reduced by antiretroviral therapy. The protein might be
      released from necrotic and apoptotic HIV-1 infected cells. HMGB1 may stimulate or
      inhibit HIV-1 replication in vitro, depending on the stage of infection, type of
      cell and purity of the protein: The protein has been suggested to reduce viral
      replication by interfering with viral entry in acute infection and to increase
      viral replication in latently infected cells. Finally, HMGB1 in combination with
      microbial products/TLR ligands seems to be associated with increased viral
      replication in vitro and in vivo.

PMID- 21198434
TI  - Accumulation of defective HIV-1 variants in a patient with slow disease
      progression.
AB  - Viral population in a long term non progressor carrying CRF02-AG HIV-1 virus
      variants with a truncated RT gene and attenuated virus replication was analyzed.
      The proportion of mutant and wild-type RT sequences was determined by clonal
      analysis of HIV-1 DNA and RNA from blood samples and peripheral blood mononuclear
      cell (PBMC) culture supernatants. Recombinant HIV-1 strains were generated by
      reverse genetics to evaluate the replicative capacity of RT variants in PBMC
      cultures. HIV-1 RNA and DNA sequences in PBMC cultures showed a mixture of stop
      codons (RT(STOP)), recombinant forms, (RT(RF)), and full length (RT(FL)) strains.
      In plasma, proportion of HIV-1 RNA sequences with a truncated RT gene fluctuated
      over time (0% in 2005, 100% in 2007 and 8.3% in 2010), while in proviral DNA was
      constant (96.5% to 100%). Reconstituted RT(STOP) strains were unable to replicate
      in PBMC. However, RT(FL) strains could trans-complement the loss of function of
      RT(STOP) variants. In vivo selection of stop codons in the RT gene resulted in
      the accumulation of replication-defective virus strains. Nevertheless, the
      observed release of defective viral particles in plasma was probably the result
      of viral protein complementation between replication-competent and replication
      incompetent HIV-1 variants. The divergence in the proportion of RT(STOP) and
      RT(FL) variants as well as in the mutation's pattern to antiretroviral drug
      resistance between HIV-1 plasma RNA and PBMC proviral DNA, suggested that
      circulating lymphocytes expressing full-length RT might be negatively selected
      for by a specific T-cell response, possibly contributing to the slow progression
      to AIDS observed in this patient.

PMID- 21198435
TI  - Divergent effects of nitric oxide donors on the biliary efflux transporters in
      isolated perfused rat livers: nitric oxide-independent inhibition of ABC
      transporters by sodium nitroprusside.
AB  - Rhodamine 123 (RH-123) and its glucuronidated metabolite (RH-Glu) are excreted
      into the bile via the ABC efflux transporters P-glycoprotein (P-gp) and multidrug
      resistance-related protein type 2 (Mrp2), respectively. In this study, we
      investigated the short-term (2 h) effects of a low or high concentration of
      nitric oxide (NO) donors sodium nitroprusside (SNP) and isosorbide dinitrate
      (ISDN) on the hepatobiliary disposition of RH-123 and its metabolite in an
      isolated perfused rat liver model. Additionally, the effects of ISDN on the
      hepatobiliary disposition of 5 (and 6)-carboxy-2', 7'- dichlorofluorescein (CDF),
      a specific marker of Mrp2, were investigated in the same model. Whereas SNP
      caused a substantial (85-90%) reduction in the P-gp- and Mrp2-mediated transport
      of RH-123 and RH-Glu, respectively, ISDN did not affect either of these
      transporters. However, ISDN reduced the biliary recovery of RH-Glu, most likely
      because of inhibition of the formation of the metabolite. Further studies showed
      that the effects of SNP on these transporters are due to a substantial (88%)
      depletion of hepatic ATP levels by this NO donor. Additionally, studies using CDF
      revealed an almost identical hepatobiliary disposition of this Mrp2 marker in the
      presence or absence of ISDN. It is concluded that short-term exposure of rat
      livers to NO does not affect the functions of the efflux transporters P-gp and
      Mrp2. The observed inhibitory effects of SNP on the functions of both P-gp and
      Mrp2 are via an NO-independent mechanism.

PMID- 21198436
TI  - Comparative pharmacokinetics and metabolism studies in lean and diet- induced
      obese mice: an animal efficacy model for 11beta-hydroxysteroid dehydrogenase type
      1 (11beta-HSD1) inhibitors.
AB  - Diet-induced obese (DIO) mice have been commonly used as an animal model in the
      efficacy assessment for new drug candidates. Although high-fat feeding has been
      reported to cause profound physiological changes, including the expression of
      drug-metabolizing enzymes, limited studies have been reported regarding the
      effect of obesity/diabetes on pharmacokinetics (PK) in animals. In this study, we
      investigated PK profiles of three 11 -HSD-1 inhibitors in the DIO mice and
      compared them to the normal lean mice. After oral administration, the in vivo
      exposure (AUC) of all three compounds was higher in DIO mice, which was
      consistent with the observed lower systemic clearance (CL) in DIO mice compared
      to lean mice. As illustrated by Compound E, a compound metabolized predominantly
      by CYP3A and 2C, the metabolic profiles for Compound E were qualitatively similar
      between DIO and lean mice, but quantitatively lower in the DIO mice. Indeed, P
      450 activities for CYP3A and 2C as well as 2D were found to be lower in liver
      microsomes prepared from DIO mice. The calculated hepatic clearance (CLH) from in
      vitro studies with liver microsomes correlated well with the observed in vivo
      clearance for both DIO and lean mice. The calculated oral bioavailability (F%)
      based on intrinsic hepatic clearance (C(LH, int)) predicted ~3 fold increase in
      F% for the DIO mice, which was comparable to the observed value. Collectively,
      these data suggest that the higher F% is most likely due to the lower first-pass
      effect in DIO mice. This study highlights the needs to take caution when
      extrapolating PK and exposure data from healthy animals to diseased animals in
      designing pharmacological studies.

PMID- 21198437
TI  - The metabolism of methazolamide - identification of metabolites in guinea pig
      urine.
AB  - The in vivo metabolism of methazolamide, a carbonic anhydrase inhibitor, was
      studied using guinea pigs as the animals. (14)C-Labeled methazolamide was
      synthesized. Eighty percent of intraperitoneally injected radioactivity was
      recovered from urine and feces within 24 hours. HPLC analysis on a C(18) column
      detected 2 radioactive metabolites (Peaks A and B). The Peaks A and B were
      isolated from the urine of the animals dosed with non-radioactive
      methazolamide.They were purified on the C(18) column. Their chemical structure
      was revealed by UV-absorbance spect a and LC/MS, and confirmed by comparing it
      with that of chemically synthesized compound. They were a glucuronide, (2
      acetylimino-3-methyl-Delta(4)-1,3,4-thiadiazol-5-yl)-1-thio-beta-D
      glucopyranosiduronic acid, and a sulfonic acid, N-[3-methyl-5-sulfo-1,3,4
      thiadiazol-2(3H)-ylidene]acetamide.

PMID- 21198438
TI  - Statin drugs, metabolic pathways, and asthma: a therapeutic opportunity needing
      further research.
AB  - The chance discovery of hydroxymethylglutaryl (HMG)-CoA reductase inhibitors has
      revolutionized the care of patients with cardiovascular disease. The unexpected
      finding that these cholesterol-lowering drugs (or 'statins') also possess
      pleiotropic immunomodulatory properties, has opened a new area of research which
      investigates the anti-inflammatory and anti-proliferative properties of statins.
      In this brief commentary, we discuss the potential application of these drugs in
      asthma, where metabolic pathways pertinent to lung inflammation, in addition to
      the mevalonate cascade, may be targeted. We review mechanisms of action, discuss
      the potential therapeutic use of statins in asthma, share some preliminary data
      from our laboratory, discuss results from recent clinical trials in asthma, and
      propose a new target asthma subpopulation that could potentially benefit. We
      conclude our essay by highlighting the mevalonate-dependent and -independent
      pathways that may be modulated by statins, including the emerging area of
      cholesterol, sphingolipid, and lipid raft biology in lung disease. In this is an
      opportunity to develop new treatments for asthma, where innovative therapies are
      urgently needed to prevent acute exacerbations and alter disease progression.

PMID- 21198439
TI  - A comparative study of the CYP450 inhibition potential of marketed drugs using
      two fluorescence based assay platforms routinely used in the pharmaceutical
      industry.
AB  - Semi-automated high throughput screening for the inhibition of major human
      cytochrome P450 enzymes (1A2, 2C9, 2C19, 2D6 and 3A4) expressed in Escherichia
      Coli (Cypex bactosomes) or human lymphoblastoid cells (Gentest cDNA microsomes)
      using fluorescent probes has been evaluated using 68 marketed drugs. In general
      lower IC50 values were obtained with Cypex bactosomes compared with Gentest cDNA
      microsomes. This could be due to use of higherconcentration of protein and also
      the lower activity of Gentest cDNA microsomes. Notably, when compared with in
      vivo clinical drug-drug interactions (cDDIs) gathered from clinical studies
      reported in the scientific literature Cypex bactosome data was better at
      predicting in vivo cDDI. Consequently, from the data obtained in this comparative
      study, a fluorescence based assay using Cypex bactosomes is more suitable as a
      front-line screen for the prediction of potential downstream CYP450 driven cDDIs.

PMID- 21198440
TI  - Mice brain nitric oxide synthase response induced by anaesthetics and other
      porphyrinogenic drugs.
AB  - Porphyrias neuropathophysiology could be related to low levels of heme as a
      cofactor for nitric oxide synthase (NOS). We examined how anaesthetics and other
      porphyrinogenic agents affect mice NOS activity and expression. Brain response
      was differential depending on the cellular fraction analyzed. Most of the drugs
      diminished cytosolic activity. Instead, isoflurane, enflurane and ethanol
      increased mitochondrial activity. NOS expression also depended on the drug
      tested. A comparative study was performed in liver. Our present and previous
      results indicate the widespread action of porphyrinogenic agents in brain, which
      could be the reason why it is difficult to establish the onset of acute porphyria
      neurological manifestations.

PMID- 21198441
TI  - An in vitro, high throughput, seven CYP cocktail inhibition assay for the
      evaluation of new chemical entities using LC-MS/MS.
AB  - A validated method for the simultaneous characterization of xenobiotic compound
      mediated inhibition of seven major cytochrome P450 (CYP) enzymes in pooled human
      liver microsomes through the use of specific CYP probe substrates (cocktail
      assay) with low protein content, and a rapid, three minute LC-MS/MS analytical
      method is described. The specific CYP substrates used in this cocktail assay
      included phenacetin (CYP1A2), bupropion (CYP2B6), amodiaquine (CYP2C8),
      tolbutamide (CYP2C9), S-mephenytoin (CYP2C19), dextromethorphan (CYP2D6), and
      midazolam (CYP3A4/5). The LC-MS method incorporated the aforementioned seven CYP
      substrates along with their respective major metabolites, and one internal
      standard, labetalol. In a cross-validation analysis, the concentrations of each
      CYP probe substrate in the assay had minimal effect (i.e., inhibition or
      activation) on the other CYP activities. Furthermore, the assay conditions for
      the multiple probe substrate, ie., cocktail assay, were validated against the
      single probe substrate assay using 18 compounds with known CYP inhibition
      liabilities and 10 proprietary compounds. The inhibitory constant (Ki) determined
      with this cocktail assay was highly correlated (R(2) >= 0.77 for each individual
      probe substrate) with that of the single probe substrate assay for all 27 CYP
      inhibitors. This seven CYP inhibition cocktail assay has increased the efficiency
      to assess compounds for inhibition of the major CYP isoforms in a high
      throughput, drug discovery setting.

PMID- 21198442
TI  - Apoptosis in carcinogenesis and cancer therapy.

PMID- 21198443
TI  - Too much of a good thing: suicide prevention promotes chemoresistance in ovarian
      carcinoma.
AB  - Ovarian cancer is the most lethal of gynecologic malignancies. Currently,
      standard treatment for epithelial ovarian cancer consists of surgical debulking
      followed by adjuvant chemotherapy with a platinum-based drug coupled with
      paclitaxel. While initial response to chemotherapy is high, the majority of
      patients develop recurrent disease which is characterized by chemoresistance. The
      primary cytotoxic effect of many chemotherapy drugs is mediated by apoptotic
      response in tumor cells. Recent data indicates that cross talk between the tumor
      microenvironment and malignant epithelial cells can influence apoptotic response
      as well. The identification of molecules involved in the regulation and execution
      of apoptosis, and their alterations in ovarian carcinoma have provided new
      insights into the mechanism behind the development of chemoresistance in this
      disease. Our challenge is now to devise strategies to circumvent cell death
      defects and ultimately improve response to treatment in ovarian carcinoma
      patients.

PMID- 21198444
TI  - Efficacy and safety of intravenous lacosamide in refractory nonconvulsive status
      epilepticus.
AB  - BACKGROUND: Lacosamide (LCM) is a novel antiepileptic drug (AED) recently
      approved as an adjunctive therapy in the treatment of partial seizures in adults.
      LCM is available in oral and intravenous formulations, has linear
      pharmacokinetics and a unique mechanism of action. THE AIM OF THIS STUDY: To
      evaluate the safety and efficacy of intravenous LCM in the treatment of
      nonconvulsive status epilepticus (NCSE) after failure of conventional therapy.
      METHODS: We retrospectively reviewed all patients with NCSE treated with LCM. We
      reviewed the clinical and electrographic changes before and after LCM
      administration. We also noted any reported side effects including
      electrocardiographic changes. RESULTS: We report four cases of NCSE that were
      refractory to conventional treatment, but readily responsive to LCM. No side
      effects attributable to LCM were identified. CONCLUSIONS: Intravenous LCM may be
      safe and efficacious as an add-on AED for the treatment of NCSE when standard
      therapy fails.

PMID- 21198445
TI  - CERAD-neuropsychological battery in screening mild Alzheimer's disease.
AB  - OBJECTIVES: The Consortium to Establish a Registry for Alzheimer's Disease
      (CERAD) neuropsychological battery (nb) is used as an evaluation tool for
      dementia. In Finland, CERAD-nb was introduced in 1999 and has been proposed to be
      used in primary health care. However, some of its parts need reassessment and
      focusing. The goal of this study was to examine the sensitivity and specificity
      of the subtests and their cut-off points most appropriate for identifying mild
      Alzheimer's disease (AD). MATERIALS AND METHODS: The study population consisted
      of 171 patients with mild AD and 315 cognitively normal elderly. Both groups
      underwent CERAD-nb investigation as a part of a wider examination procedure.
      RESULTS: The most efficient subtests to discriminate patients with mild AD from
      the normal elderly were Wordlist delayed recall and savings, Wordlist learning
      and Wordlist recognition and a new variable of Total recall. Optimal cut-off
      points for each subtest are suggested. The sensitivities of the verbal memory
      subtests varied between 0.75 and 0.94, the specificities between 0.80 and 0.93
      and the areas under the receiver operating characteristics curve between 0.89 and
      0.96. CONCLUSIONS: The CERAD-nb is capable of differentiating cases with mild AD
      from normal elderly individuals particularly with its verbal memory subtests. New
      cut-off scores for CERAD's subtests validated in the study further enhance the
      differentiating power, and with these clarifications, CERAD-nb is considered
      appropriate to be used as a screening tool for AD even in primary health care.

PMID- 21198446
TI  - Impaired body image in patients with multiple sclerosis.
AB  - OBJECTIVE: Despite the growing research on body image disturbances in chronically
      ill patients, reports of such disturbances in patients with multiple sclerosis
      (MS) are scarce. The aim of this study was to assess the occurrence of different
      aspects of body image disturbances in patients with MS, taking into account the
      disability status as well as depressive symptoms. MATERIALS & METHODS: Forty
      patients with MS and 28 healthy controls were investigated with questionnaires
      assessing attractiveness/self-confidence, accentuation of external appearance,
      worries about possible physical deficits, sexual problems, vitality and
      depressive symptoms. In MS patients, medical parameters like the expanded
      disability status were assessed too. RESULTS: In comparison with healthy
      controls, the MS patients, being although only mildly disabled and in a quite
      stable mood, reported significantly higher worries about physical deficits,
      described a significantly worse body appraisal and significantly more sexual
      problems. While female MS patients predominantly suffered from worries concerning
      physical deficits and feelings of being less attractive, sexual problems were of
      particular concern in male MS patients. CONCLUSIONS: Even mildly impaired MS
      patients who are not markedly depressed have to deal with problems of body image.
      Improvement of body image perception in MS patients taking gender-specific
      differences into account represents a promising area of future psychological
      research.

PMID- 21198447
TI  - The prognostic value of pulsatility index, flow velocity, and their ratio,
      measured with TCD ultrasound, in patients with a recent TIA or ischemic stroke.
AB  - BACKGROUND - Increased flow velocities, and combinations of low mean flow
      velocity (MFV) and a high pulsatility index (PI) are associated with intracranial
      arterial disease. We investigated the association of MFV and the ratio of PI and
      MFV (PI-MFV ratio) in the middle cerebral artery (MCA) with recurrence of
      vascular events in patients with a transient ischemic attack (TIA) or minor
      ischemic stroke. METHODS - Five hundred and ninety-eight consecutive patients
      underwent TCD investigation. Outcome events were fatal or non-fatal stroke and
      the composite of stroke, myocardial infarction, or vascular death (major vascular
      events). Hazard ratios (HR) were estimated with Cox proportional hazards multiple
      regression method, adjusted for age, gender, and vascular risk factors. RESULTS -
      TCD registration was successful in 489 patients. Mean follow-up was 2.1 years.
      Cumulative incidence was 9% for all stroke and 12% for major vascular events. MFV
      over 60.5 cm/s increased the risk for both stroke (HR 2.8; 95% CI: 1.3-6.0) and
      major vascular events (HR 2.6; 95% CI: 1.3-5.0). Each unit increase in PI-MFV
      ratio was associated with a HR 2.8 (95% CI: 1.7-4.8) for stroke and HR 2.2 (95%
      CI: 1.3-3.6) for major vascular events. CONCLUSION - In patients with a TIA or
      non-disabling ischemic stroke, MFV and the PI-MFV ratio in the MCA are
      independent prognostic factors for recurrent vascular events.

PMID- 21198448
TI  - Sudden sensorineural hearing loss in multiple sclerosis: clinical course and
      possible pathogenesis.
AB  - OBJECTIVE - To assess the symptom of sudden hearing loss in multiple sclerosis
      (MS). METHOD - We reviewed patient files in our MS clinic between January 2004
      and November 2009 for symptoms of sudden hearing loss. RESULTS - We were able to
      identify 11 of 253 patients (4.35%) with sudden hearing loss. In seven patients,
      the hearing decline was the presenting symptom of MS and in all 11 patients, it
      appeared early in the course of the disease. There was no residual hearing
      deficit in 9/11 patients. In no patient was the condition bilateral and in none
      did it recur. CONCLUSION - Episodes of hearing loss are not uncommon in MS and
      have a good chance of complete recovery.

PMID- 21198449
TI  - Cerebrovascular reactivity to l-arginine in the anterior and posterior cerebral
      circulation in migraine patients.
AB  - OBJECTIVE - Cerebral infarction preferentially affects the posterior cerebral
      artery distribution in migraine patients. The results obtained from the few known
      studies that have compared the anterior and posterior cerebral endothelial
      function are contradictory. To the best of our knowledge, cerebrovascular
      reactivity to L-arginine (CVR), measured by transcranial Doppler sonography
      (TCD), has not been previously used to determine the posterior cerebral
      endothelial function in migraine patients with (MwA) and without aura (MwoA).
      MATERIALS AND METHODS -  Forty migraine patients without comorbidities (20 MwA,
      20 MwoA) and 20 healthy subjects were included. By employing strict inclusion
      criteria, we avoided the possible vascular risk factors. Mean arterial velocity
      in the middle cerebral artery (MCA) and the posterior cerebral artery (PCA) was
      measured by TCD before and after infusion of L-arginine, and CVR to L-arginine
      was then calculated. RESULTS - All migraine patients had lower CVR to L-arginine
      in PCA (P = 0.002) and similar in MCA (P = 0.29) compared to healthy subjects.
      This difference was also present in MwA and MwoA compared to healthy subjects (P
      = 0.003). CONCLUSIONS -  Lower CVR to L-arginine in PCA in migraine patients
      could associate migraine and cerebral infarcts that are more common in the
      posterior cerebral artery distribution.

PMID- 21198450
TI  - Change of the melanocortin system caused by bilateral subthalamic nucleus
      stimulation in Parkinson's disease.
AB  - OBJECTIVES - Determine whether bilateral subthalamic nucleus stimulation (STN
      DBS) in Parkinson's disease (PD) is associated with an increase in neuropeptide Y
      (NPY) and/or resistance to inhibition by leptin in relation to post-surgery
      weight gain. MATERIALS AND METHODS - This prospective study included 20 patients
      who underwent bilateral STN-DBS and 17 who refused surgery. Data were obtained at
      baseline, 3 and 6 months on neurological and nutritional status, including
      determination of body mass index (BMI) and serum NPY and leptin levels. RESULTS -
      NPY and leptin levels changed over time, with a distinct pattern. The BMI
      increase at 6 months was greater in the surgical group (5.5 +/- 6.3% vs 0.5 +/-
      3.5%; P = 0.035). Medical group exhibited a reduction in leptin level (-2.0 +/-
      4.3 ng/ml) and a consequent increase in NPY level (72.4 +/- 58.7 pmol/ml).
      However, STN-DBS patients showed an increase in leptin (3.1 +/- 5.0 ng/ml; P =
      0.001 vs medical group) and also in NPY (12.1 +/- 53.6 pmol/ml; P = 0.022 vs
      medical group) levels, which suggests resistance to inhibition by leptin. Rise in
      NPY level correlated with higher stimulation voltages. CONCLUSIONS -  Bilateral
      STN-DBS causes disruption of the melanocortin system, probably related to
      diffusion of the electric current to the hypothalamus. This mechanism may in part
      explain the weight gain of patients with PD after surgery.

PMID- 21198451
TI  - The need for publishing the silent evidence from negative trials.

PMID- 21198452
TI  - Suggestive evidence on the genetic link between mitochondria dysfunction and
      autism.

PMID- 21198453
TI  - Abnormalities in task-related neural network formation in schizophrenia.

PMID- 21198455
TI  - Association between cannabis and psychiatric hospitalization.
AB  - OBJECTIVE: To investigate the relationship between cannabis use and mental
      health. METHOD: A cross-sectional analysis in a sample of 17 698 individuals with
      a mean age of 22 years (SD: 4.2). Participants provided information on the amount
      and initial age of cannabis use and history of psychiatric hospitalizations
      through a web-based questionnaire. To quantify Delta(9) -tetrahydrocannabinol
      exposure, we operationalized cannabis use as the amount of money spent on
      cannabis per week over the last month. The odds ratio of having a history of
      psychiatric hospitalizations was the primary outcome measure. RESULTS: We found a
      dose-response relationship between the amount of cannabis use and the odds for
      psychiatric hospitalization. Adjusted odds ratios for hospitalization increased
      with the amount of cannabis consumed from 1.6 (95% CI: 1.1-2.3) in incidental
      users to 6.2 (95% CI: 4.3-8.9) in heavy users (>?25/week). Our data suggested
      that concomitant drug use was an intermediate factor. Exposure to cannabis before
      the age of 12 years was found to carry a 4.8 (95% CI: 2.9-7.8) times increased
      odds for past psychiatric hospitalizations. CONCLUSION: We conclude that early
      and heavy uses of cannabis are each and independently associated with poor mental
      health in its users.

PMID- 21198456
TI  - SSRIs in late pregnancy: the risk of neonatal respiratory distress and seizures.

PMID- 21198457
TI  - Borderline personality disorder traits and their relationship with dimensions of
      normative personality: a web-based cohort and twin study.
AB  - OBJECTIVE: To describe the structure of genetic and environmental risk factors
      for four dimensions of borderline personality disorder (BPD) and to understand
      the source of resemblance of these dimensions and normal personality. METHOD: A
      web-based sample (n = 44,112 including 542 twin pairs) completed items from 4
      scales of the Dimensional Assessment of Personality Pathology Basic Questionnaire
      and the Big Five Inventory. RESULTS: A one-factor common pathway model best fits
      the 4 BPD scales producing a highly heritable latent liability (heritability =
      60%) and strong loadings on all 4 dimensions. Affective instability had the
      lowest trait-specific genetic loading, suggesting that it was a core feature of
      BPD. A complex pattern of genetic and environmental associations was found
      between the big five personality traits and BPD dimensions. The strongest genetic
      correlations with the BPD traits were generally seen for neuroticism (positive),
      followed by conscientiousness and agreeableness, both negative. CONCLUSION: In
      the general population, these four BPD dimensions reflect one underlying highly
      heritable factor. The association between normative personality and dimensions of
      BPD is complex with high degrees of genetic correlation.

PMID- 21198458
TI  - CSF biomarkers in suicide attempters--a principal component analysis.
AB  - OBJECTIVE: The objective of the present study was to identify biological patterns
      (factors) among 20 cerebrospinal fluid (CSF) biomarkers in suicide attempters and
      subsequently analyse their association with suicidal behaviour. METHOD: We
      measured kynurenic acid, orexin, homovanillic acid (HVA), 5-hydroxyindoleacetic
      acid (5-HIAA), 3-methoxy-4-hydroxyphenylglycol, chemokines, matrix
      metalloproteases and cytokines in the CSF of 124 drug-free suicide attempters.
      Patients were evaluated for suicidality and psychiatric symptoms using well
      defined psychiatric rating scales and followed-up regarding future suicide. We
      used principal component analysis to identify factors among the biological
      substances. RESULTS: Four factors were extracted from the 20 biomarkers,
      explaining 52.4% of the total variance. Factors 1 and 2 were characterized by
      high loadings of chemokines and cytokines respectively. They were both associated
      with severe depressive symptoms. Factor 2 was also associated with a high
      suicidal intent. Factor 4 was characterized by strong loadings of the monoamine
      metabolites 5-HIAA and HVA, as well as orexin and interleukin-6. High scores on
      this factor were found in patients who performed a violent suicide attempt and in
      patients who subsequently completed suicide. CONCLUSION: Our results suggest that
      specific combinations of CSF biomarkers may discriminate between types of
      suicidal behaviour and indicate increased risk for future suicide.

PMID- 21198459
TI  - Cognitive hostility and suicide.
AB  - OBJECTIVE: To determine whether a specific component of hostility (i.e. cognitive
      or behavioural) may predict suicide in a prospective design, controlling for
      depressive mood. METHOD: In 1993, 14,752 members of the 'GAZ et ELectricite'
      (GAZEL) cohort (10,819 men, mean age=49.0 years; 3933 women, mean age=46.2 years)
      completed the Center for Epidemiologic Studies Depression Scale and at least one
      subscale (i.e. cognitive or behavioural hostility) of the Buss and Durkee
      Hostility Inventory. Dates and causes of death were obtained annually. RESULTS:
      During a mean follow-up of 15.7 years, 28 participants completed suicide (24 men,
      four women). Suicide was predicted by depressive mood [relative index of
      inequality (RII) (95% CI)=8.16 (1.97-33.85)] and cognitive hostility [RII (95%
      CI)=10.76 (2.50-46.42)], but not behavioural hostility [RII (95% CI)=1.37 (0.38
      4.97)]. These associations remained significant after adjustment for potential
      confounders. After mutual adjustment, however, suicide remained significantly
      associated with cognitive hostility [RII (95% CI)=8.87 (1.52-51.71)] (RII
      reduction: 34.6%), but no longer with depressive mood [RII (95% CI)=2.03 (0.41
      10.07)] (RII reduction: 79.1%). CONCLUSION: Cognitive rather than behavioural
      hostility is associated with an increased risk of suicide, independently of
      baseline depressive mood.

PMID- 21198460
TI  - Increasing kyphosis predicts worsening mobility in older community-dwelling
      women: a prospective cohort study.
AB  - OBJECTIVES: To determine whether increasing kyphosis angle was independently
      associated with poorer mobility as measured according to the Timed Up and Go Test
      (TUG), after controlling for other established risk factors. DESIGN: Prospective
      cohort study. SETTING: Eleven clinical centers in the United States.
      PARTICIPANTS: Two thousand seven hundred seventy-seven women aged 55 to 80
      randomized to the placebo arms of the Fracture Intervention Trial, a randomized
      controlled trial of the effect of alendronate on risk for osteoporotic fractures.
      MEASUREMENTS: The primary predictor was change in kyphosis angle, measured using
      the Debrunner Kyphometer; the outcome was change in mobility, measured as
      performance time on the TUG. Covariates were baseline age, kyphosis angle, body
      mass index (BMI), self-reported health status, grip strength, change in total hip
      bond mineral density (BMD), and number of vertebral fractures over a mean of 4.4
      years. RESULTS: Greater kyphosis angle predicted longer mobility performance
      times (P<.001), independent of other significant predictors of worsening mobility
      including age, baseline kyphosis, health status, grip strength, BMI, change in
      hip BMD, and new vertebral fractures. TUG performance times increased by 0.02
      seconds (95% confidence interval (CI)=0.01-0.03) for every 5 degrees  increase in
      kyphosis angle, more than the increase in mobility time of 0.01 seconds (95%
      CI=0.005-0.03) over 1 year observed in this cohort. CONCLUSION: Increasing
      kyphosis angle is independently associated with worsening mobility. Interventions
      are needed to prevent or reduce increasing kyphosis and mobility decline.

PMID- 21198461
TI  - Use of mental health care by community-dwelling older adults.
AB  - OBJECTIVES: To examine relationships between perceived need for care, illness
      characteristics, attitudes toward care, and probability that older adults will
      use mental health care (MHC). DESIGN: Secondary data analysis. SETTING: The
      Collaborative Psychiatric Epidemiology Surveys (2001-2003). PARTICIPANTS: One
      thousand six hundred eighty-one community-dwelling adults aged 65 and older.
      MEASUREMENTS: Self-reported MHC use and perceived need for care in the previous
      12 months, previous year and history of mental illness, history of physical
      illness, attitudes toward care, and sociodemographic characteristics. RESULTS: Of
      the entire sample, 6.5% had received some type of MHC in the previous year,
      although 65.9% of those with major depressive disorder (MDD) and 72.5% with
      anxiety did not receive MHC. In respondents with previous-year depression or
      anxiety, use was less likely for those with low World Health Organization
      Disability Assessment Scale (WHO-DAS) self-care ability. Use was more likely for
      those with more chronic physical conditions and worse WHO-DAS cognitive capacity.
      Seventeen percent of those with perceived need for MHC did not receive it. In
      respondents with perceived need, subthreshold generalized anxiety disorder was
      associated with lower likelihood of use. Use was more likely for older
      respondents and those with more household members, at least a high school
      education, and better self-care ability. Forty-one percent of those who perceived
      a need for care but did not use it met previous-year diagnostic criteria for
      anxiety, and 17% met criteria for MDD. CONCLUSION: Understanding the perceptions
      that underlie individuals' health care-seeking behavior is an important step
      toward reducing underuse of MHC by older adults.

PMID- 21198462
TI  - Presence of in-home caregiver and health outcomes of older adults with chronic
      obstructive pulmonary disease.
AB  - OBJECTIVES: To determine whether the presence of in-home caregivers is associated
      with changes in the health outcomes of older adults with chronic obstructive
      pulmonary disease (COPD). DESIGN: Cross-sectional study. SETTING: Geriatric
      medical center and academic respiratory clinic in Japan. PARTICIPANTS: Community
      dwelling adults with COPD and their caregivers. MEASUREMENTS: Outcome measures
      (pulmonary function tests, distance on the 6-minute walking test (6MWT),
      activities of daily living (ADLs), quality of life (Medical Outcomes Study 36
      item Short Form Survey and St. George's Respiratory Questionnaire), and
      frequencies of emergency visits and hospitalizations of those living alone (group
      A), those living with one caregiver (group B), and those living with two or more
      caregivers (group C) were compared. RESULTS: Three hundred eighty-nine
      participants (315 men and 74 women; mean age 73.3) were enrolled. Mean predicted
      forced expiratory volume in 1 second was 57.5%. The numbers of participants
      allocated into the global initiative for chronic obstructive lung disease stages
      I, II, III, and IV were 105, 107, 122, and 55, respectively. Group A had 87
      participants; group B, 125; and group C, 177. Instrumental ADL scores were
      highest in group A (P < .001), whereas 6MWT distance was longest in group B and
      shortest in group A. The frequency of emergency visits was highest in group A (P
      < .001). CONCLUSION: Participants with COPD living alone were higher functioning
      in terms of instrumental ADLs, but they had less exercise capacity and more
      frequent emergency visits than participants in the in-home caregiver groups and
      no difference in hospitalizations.

PMID- 21198464
TI  - Geriatrics medication management rounds: a novel approach to teaching rational
      prescribing with the use of the medication screening questionnaire.
AB  - Prescribing for older adults has become increasingly complex as treatment
      regimens have intensified, and the use of herbal and over-the-counter medications
      has increased. This article describes an educational intervention called
      Geriatrics Medication Management Rounds, which uses a new and comprehensive
      assessment tool called the Medication Screening Questionnaire (MSQ). This case
      based interactive session is aimed at teaching trainees and postgraduate
      physicians and pharmacists to examine the pharmacology, potential drug and
      disease interactions, efficacy, adherence issues, and goals of care for a
      geriatric patient's medication regimen. Twenty-three sessions were held from
      January 2008 to January 2009, with 241 participants overall and an average of
      10.4 participants per session. Of the 163 participants who completed an
      evaluation, all agreed or strongly agreed that the learning goals were clearly
      established, and 99% agreed or strongly agreed that the overall quality of the
      session was excellent. Participants described the sessions as excellent,
      interactive, informative, and educational. Teaching medication management through
      a case-based format with the MSQ is an effective format that is interactive and
      informative, as demonstrated by positive quantitative and qualitative
      evaluations. These sessions may be replicated in other settings and with other
      disciplines.

PMID- 21198463
TI  - The effect of state policies on nursing home resident outcomes.
AB  - OBJECTIVES: To test the effect of changes in Medicaid reimbursement on clinical
      outcomes of long-stay nursing home (NH) residents. DESIGN: Longitudinal,
      retrospective study of NHs, merging aggregated resident-level quality measures
      with facility characteristics and state policy survey data. SETTING: All free
      standing NHs in urban counties with at least 20 long-stay residents per quarter
      (length of stay > 90 days) in the continental United States between 1999 and
      2005. PARTICIPANTS: Long-stay NH residents INTERVENTIONS: Annual state Medicaid
      average per diem reimbursement and the presence of case-mix reimbursement in each
      year. MEASUREMENTS: Quarterly facility-aggregated, risk-adjusted quality-of-care
      measures surpassing a threshold for functional (activity of daily living)
      decline, physical restraint use, pressure ulcer incidence or worsening, and
      persistent pain. RESULTS: All outcomes showed an improvement trend over the study
      period, particularly physical restraint use. Facility fixed-effect regressions
      revealed that a $10 increase in Medicaid payment increased the likelihood of a NH
      meeting quality thresholds by 9% for functional decline, 5% for pain control, and
      2% for pressure ulcers but not reduced use of physical restraints. Facilities in
      states that increased Medicaid payment most showed the greatest improvement in
      outcomes. The introduction of case-mix reimbursement was unrelated to quality
      improvement. CONCLUSION: Improvements in the clinical quality of NH care have
      been achieved, particularly where Medicaid payment has increased, generally from
      a lower baseline. Although this is a positive finding, challenges to implementing
      efficient reimbursement policies remain.

PMID- 21198465
TI  - Extracorporeal membrane oxygenation for respiratory failure: past, present and
      future.

PMID- 21198466
TI  - Should routine pre-operative testing be abandoned?

PMID- 21198467
TI  - ARDS, acronyms and the Pinocchio effect.

PMID- 21198468
TI  - Evaluation of a transportable capnometer for monitoring end-tidal carbon dioxide.
AB  - We compared a small and transportable Capnometer (EMMATM) with a reference
      capnometer, the Siesta i TS Anaesthesia. During air-breathing through a facemask,
      both the EMMA (nine modules) and reference capnometer sampled expired gas
      simultaneously. A wide range of end-tidal carbon dioxide values were obtained
      during inhalation of carbon dioxide and voluntary hyperventilation. The median
      IQR [range] difference between all sets of carbon dioxide values (EMMA -
      reference) was -0.3 (-0.6 to 0.0 [-1.7 to 1.6] kPa; n = 297) using new batteries,
      which was statistically significant (p = 0.04) and located to two of the nine
      EMMAs tested. Using batteries with reduced voltage did not influence the
      measurements. The 95% CI of the medians of the differences were -0.4 to -0.2. We
      conclude that the EMMA can slightly under-read the end-tidal carbon dioxide but
      is generally comparable with a free-standing monitor. The precision of the EMMAs
      was similar whether new batteries or batteries with reduced voltage were used.

PMID- 21198469
TI  - Subclavian cannulation with ultrasound: a novel method.

PMID- 21198470
TI  - What's hot and what's not: pitfalls in infrared tympanic thermometry.

PMID- 21198471
TI  - Cardiac arrest following stellate ganglion block performed under ultrasound
      guidance.

PMID- 21198472
TI  - Rivaroxaban for thromboembolism prophylaxis after orthopaedic surgery.

PMID- 21198473
TI  - Sedation by non-anaesthetists: an unacceptable risk?

PMID- 21198474
TI  - Failure to ventilate with the Draeger Oxylog 2000 transport ventilator.

PMID- 21198475
TI  - Postoperative analgesia following shoulder surgery.

PMID- 21198477
TI  - Fire risk during eye surgery.

PMID- 21198478
TI  - Solution for dissolving teicoplanin.

PMID- 21198479
TI  - Satisfaction guaranteed? a patient survey of the anaesthesia service.

PMID- 21198480
TI  - Dural puncture with occluded Tuohy needle.

PMID- 21198481
TI  - Editorial: Need(le)less confusion.

PMID- 21198482
TI  - Editorial: Farewell to history.

PMID- 21198483
TI  - A survey of the management of needlestick injuries from incapacitated patients in
      intensive care units.
AB  - The Human Tissue Act 2004 and Mental Capacity Act 2005 resulted in a change in
      the management of needlestick injuries sustained from incapacitated patients. It
      appears unlawful to test for blood-borne viruses without a patient's consent for
      the sole benefit of the healthcare worker. This survey of intensive care units
      within England, Wales and Northern Ireland investigated how needlestick injuries
      from incapacitated patients had been managed within the previous year. Of the 225
      intensive care units surveyed, 99 (44%) responded. Sixty-two (62.6%) reported a
      needlestick injury to a healthcare worker from an incapacitated patient. Thirty
      six (64.3%) patients were tested for blood-borne viruses without consent. Sixteen
      (25.8%) patients tested positive for blood-borne viruses. Only 19 (30.6%)
      healthcare workers took post-exposure prophylaxis following the injury. These
      results show that needlestick injuries from incapacitated patients are common and
      that the majority of patients were tested for blood-borne viruses without
      consent.

PMID- 21198484
TI  - The ability of anaesthetists to identify the position of the right internal
      jugular vein correctly using anatomical landmarks.
AB  - We performed a study of 85 consenting anaesthetists to assess their ability to
      locate the right internal jugular vein using a landmark technique. Initially, a
      questionnaire was completed ascertaining previous user experience. An ultrasound
      probe, using the midpoint as an 'imaginary needle', was placed on the neck of a
      healthy volunteer (with previously confirmed normal anatomy) and the image
      recorded. Both anaesthetist and volunteer were blinded to the screen until the
      image was stored. Anaesthetists were grouped into those in training before 2002
      (Pre-2002, n = 58), when National Institute for Health and Clinical Excellence
      guidelines recommending ultrasound guidance were published, and those training
      after this time point (Post-2002, n = 27). The success rate for identifying the
      internal jugular vein using the landmark technique was 36/58 (62%) in the Pre
      2002 group and 6/27 (22%) in the Post-2002 group (p < 0.001). Three participants
      in each group would have hit the carotid artery (5% Pre-2002 and 11% Post-2002
      respectively; p = 0.2). The advent of routine use of ultrasound has resulted in a
      cohort of anaesthetists who are unable to use a landmark technique effectively or
      safely. This has significant training implications.

PMID- 21198486
TI  - Bench study of ventilation in simulated upper airway obstruction.

PMID- 21198485
TI  - Can sugammadex save a patient in a simulated 'cannot intubate, cannot ventilate'
      situation?
AB  - Recent studies have shown that the use of high dose rocuronium followed by
      sugammadex provides a faster time to recovery from neuromuscular blockade
      following rapid sequence induction than suxamethonium. In a manikin-based 'cannot
      intubate, cannot ventilate' simulation, we studied the total time taken for
      anaesthetic teams to prepare and administer sugammadex from the time of their
      initial decision to use the drug. The mean (SD) total time to administration of
      sugammadex was 6.7 (1.5) min, following which a further 2.2 min (giving a total
      8.9 min) should be allowed to achieve a train-of-four ratio of 0.9. Four (22%)
      teams gave the correct dose, 10 (56%) teams gave a dose that was lower than
      recommended, four (22%) teams gave a dose that was higher than recommended, six
      (33%) teams administered sugammadex in a single dose, and 12 (67%) teams gave
      multiple doses. Our simulation highlights that sugammadex might not have saved
      this patient in a 'cannot intubate, cannot ventilate' situation, and that
      difficulties and delays were encountered when identifying, preparing and
      administering the correct drug dose.

PMID- 21198488
TI  - Use of a Venner A.P. Advance videolaryngoscope in a patient with potential
      cervical spine injury.

PMID- 21198490
TI  - The anaesthetist and the environment.

PMID- 21198489
TI  - Anaesthesia, the environment, and our carbon footprint.

PMID- 21198491
TI  - Comparison of the C-MAC videolaryngoscope with the Macintosh, Glidescope and
      Airtraq laryngoscopes in easy and difficult laryngoscopy scenarios in manikins.

PMID- 21198494
TI  - Modification of Tp-e and QTc intervals during caesarean section under spinal
      anaesthesia.

PMID- 21198496
TI  - Desaturation during rapid sequence induction of anaesthesia.

PMID- 21198497
TI  - Litigation related to regional anaesthesia: careful reading and interpretation
      needed.

PMID- 21198499
TI  - Bicarbonate causing precipitation in epidural top-up solutions.

PMID- 21198500
TI  - Awareness of local anaesthetic toxicity issues among hospital staff.

PMID- 21198501
TI  - Amniotic fluid embolism - an update.

PMID- 21198502
TI  - Reducing major procedural complications from central venous catheterisation.

PMID- 21198503
TI  - Venous air embolism during semi-sitting craniotomy evokes thrombocytopenia.
AB  - Venous air embolism activates platelets in vitro and can evoke platelet
      dysfunction in swine. We tested the hypothesis that venous air embolism during
      semi-sitting craniotomy induces thrombocytopenia in humans. We analysed the
      charts of 799 patients who had an elective craniotomy in the semi-sitting
      position between 1990 and June 2009. Venous air embolism occurred in 52 patients
      (6.5%) and was associated with a decrease in mean (SD) in platelet count from 270
      (75) * 109 l-1 to 194 (62) * 109 l-1 (p < 0.001). In age-matched controls without
      venous air embolism mean (SD) platelet count did not change (254 (82) * 109 l-1
      vs. 250 (97) * 109 l-1 (NS). While mean (SD) haematocrit fell slightly in both
      groups (venous air embolism: 0.40 (0.05) to 0.32 (0.04), p <0.001; no venous air
      embolism: 0.41 (0.04) to 0.35 (0.05), p < 0.001), normalising platelet count to
      haematocrit did not alter the results.

PMID- 21198504
TI  - Litigation related to central venous access by anaesthetists: an analysis of
      claims against the NHS in England 1995-2009.

PMID- 21198505
TI  - Unexpected failure of rocuronium-mediated neuromuscular blockade.

PMID- 21198506
TI  - Airway emergency during anaesthesia using a metered-dose inhaler.

PMID- 21198507
TI  - Non-Luer neuraxial equipment and anaesthetists' attitudes to change.

PMID- 21198508
TI  - A complicated case of chlorhexidine-associated anaphylaxis.

PMID- 21198509
TI  - A novel use for the Apple (4th generation) iPod Touch in the operating room.

PMID- 21198510
TI  - Postoperative analgesia for shoulder surgery - some observations.

PMID- 21198512
TI  - Interpleural analgesia following hepatic resection.

PMID- 21198514
TI  - Laryngospasm in an unsedated patient during elective cannula cricothyroidotomy.

PMID- 21198515
TI  - Genetic studies of Prader-Willi patients provide evidence for conservation of
      genomic architecture in proximal chromosome 15q.
AB  - Prader-Willi syndrome (PWS) is a neurogenetic disorder associated with recurrent
      genomic recombination involving low copy repeats (LCRs) located in the human
      chromosome 15q11-q13. Previous studies of PWS patients from Asia suggested that
      there is a higher incidence of deletion and lower incidence of maternal
      uniparental disomy (mUPD) compared to that of Western populations. In this
      report, we present genetic etiology of 28 PWS patients from Taiwan. Consistent
      with the genetic etiology findings from Western populations, the type II deletion
      appears to be the most common deletion subtype. Furthermore, the ratio of the two
      most common deletion subtypes and the ratio of the maternal heterodisomy to
      isodisomy cases observed from this study are in agreement with previous findings
      from Western populations. In addition, we identified and further mapped the
      deletion breakpoints in two patients with atypical deletions using array CGH
      (comparative genomic hybridization). Despite the relatively small numbers of
      patients in each subgroup, our findings suggest that the genomic architecture
      responsible for the recurrent recombination in PWS is conserved in Taiwanese of
      the Han Chinese heritage and Western populations, thereby predisposing chromosome
      15q11-q13 to a similar risk of rearrangements.

PMID- 21198517
TI  - The use of intravenous immunoglobulin for treatment of dermatological conditions
      in Australia: A review.
AB  - Intravenous immunoglobulin has been used in the treatment of various
      dermatological conditions, including toxic epidermal necrolysis, bullous
      pemphigoid and pemphigus vulgaris. From March 2008, the National Blood Authority
      has implemented the 'Criteria for the clinical use of intravenous immunoglobulins
      in Australia'. The new criteria have formalized the eligibility requirements for
      several dermatological conditions. This may increase access to intravenous
      immunoglobulin for treatment for these conditions. However, there remain
      stringent eligibility criteria with which dermatologists need to be acquainted.
      In some conditions, dermatology review is mandated by these criteria while in
      other conditions with skin manifestations, referral to other specialists is
      required. The following article provides a summary of the salient points in
      relation to the clinical use of intravenous immunoglobulin in dermatology, as
      well as its production and supply in Australia.

PMID- 21198518
TI  - Antigliadin antibodies in psoriasis.
AB  - BACKGROUND/OBJECTIVES: Although antigliadin antibodies (AGA) are markers of
      coeliac disease, elevated levels of these antibodies are also seen in many other
      autoimmune, neurological, haematological, collagen vascular and cutaneous
      disorders, even in the absence of clinically overt gastrointestinal disease.
      Several studies have reported an association between psoriasis and AGA, with
      improvement in severity of psoriasis on a gluten-free diet. This study aims to
      determine whether patients with psoriasis in Kashmir have an increased prevalence
      of elevated AGA. METHODS: A total of 120 patients (all native Kashmiris) with
      psoriasis and an equal number of age- and sex-matched controls without any
      personal or family history of autoimmune disorders were included in the study.
      Both groups were tested for IgA and IgG AGAs using a standard enzyme-linked
      immunosorbent assay method. RESULTS: No statistically significant difference in
      the prevalence of AGA among patients with psoriasis (6.67% for IgA and 4.17% for
      IgG) and control group individuals (7.5% IgA and 5.0% IgG) was observed. The mean
      AGA levels in the two groups were not statistically different. Furthermore, no
      significant association between AGA levels and psoriasis severity, joint
      involvement, age of onset of psoriasis or arthritis was observed. CONCLUSIONS:
      The results of our study show that AGA are not elevated in psoriasis patients as
      compared with a healthy population, and there is no association between AGA and
      psoriasis, its onset, severity and joint symptoms.

PMID- 21198520
TI  - Adverse effects of isotretinoin: A retrospective review of 1743 patients started
      on isotretinoin.
AB  - BACKGROUND/OBJECTIVES: Isotretinoin has revolutionized the management of acne
      vulgaris. However, concerns continue regarding the adverse effect profile of
      isotretinoin. This study aims to review the adverse effects experienced by
      patients started on isotretinoin by a single dermatologist. METHODS:
      Retrospective chart review of 1743 patients started on isotretinoin for various
      dermatological conditions over a 6-year period. Details of the dose of
      isotretinoin used, concomitant medications, adverse effects and outcome were
      recorded. RESULTS: One-fifth (18.5%) of patients reported no adverse effects
      during the study period. Cheilitis was the most commonly reported adverse effect,
      affecting 78% of users, followed by eczema and tiredness, seen in 12% each.
      However, these were clearly dose-dependent, as the group treated with doses of
      isotretinoin under 0.25 mg/kg/day only reported cheilitis in 47%, eczema in 7%
      and tiredness in 5%, compared with 96%, 16% and 18%, respectively, in those
      treated with more than 0.75 mg/gm/day. Twenty-four patients (1.4%) stopped
      isotretinoin because of adverse effects; a further three patients complained of
      severe adverse effects on at least one occasion, but continued taking the
      medication. The adverse effect(s) that led to patients stopping isotretinoin were
      cheilitis (22 patients), mood change (13), tiredness (12), eczema (6) and
      pregnancy (2). There were no reported instances of suicidal ideation or attempted
      suicide. CONCLUSIONS: Other than the two oral contraceptive failures, there were
      no serious adverse events recorded during this review period. Isotretinoin is a
      very effective medication with a low adverse-effect profile when used at lower
      doses.

PMID- 21198519
TI  - Basement membrane zone and dermal extracellular matrix of the vulva, vagina and
      amnion: An immunohistochemical study with comparison with non-reproductive
      epithelium.
AB  - BACKGROUND/OBJECTIVES: The basement membrane zone (BMZ) is an anatomically
      defined region present in all types of skin and mucosa, linking the epithelium to
      the mesenchyme with a complex structure to provide adhesion. Altered antigenic
      expression of the BMZ is implicated in interface dermatoses, and the BMZ is
      targeted by autoantibodies in subepidermal immunobullous dermatoses. This study
      aims to compare the antigenic expression of the BMZ and the dermal extracellular
      matrix in female genital skin and mucosa and amnion, with non-reproductive skin
      and mucosa. METHODS: An indirect immunofluorescence technique was used to compare
      the antigenic expression of hemidesmosome, lamina lucida, anchoring filaments,
      lamina densa, anchoring fibrils and extracellular matrix in samples of non
      reproductive skin (three), oral mucosa (three), vulval skin (two), vagina (three)
      and amnion (four). RESULTS: Antigenic expression was similar in the stratified
      epithelium of reproductive and non-reproductive skin and mucosa, but differed in
      the simple cuboidal epithelium of amnion, which had reduced expression of dermal
      associated antigens. CONCLUSIONS: The BMZ and dermal extracellular matrix of
      vagina and vulva are very similar to those of non-reproductive skin and mucosa
      despite their various functions, but differs from amnion. Their antigenic
      expression does not fully account for the anatomical distribution of
      immunobullous and interface dermatoses.

PMID- 21198521
TI  - Risk factors in a cohort of patients with multiple primary melanoma.
AB  - BACKGROUND: There are various known familial and environmental risk factors that
      influence the risk for melanoma. This study sought to define the risk factors for
      multiple primary melanoma. METHODS: A telephone survey of patients with multiple
      primary melanomas was conducted from a private practice in south-east Queensland,
      in order to examine various risk factors in this cohort. RESULTS: Our findings of
      high rates of family history of melanoma (37%), and of dysplastic naevi (42%)
      support the influence of genotype in this high-risk group. A family history of
      multiple primary melanomas, seen in 17% of our patients, is a risk factor not
      previously reported in similar cohort studies. Sixty-eight per cent of patients
      had an equal or lesser degree of invasive malignancy in subsequent melanomas.
      Most multiple primary melanoma patients in this group (86.6%) were conducting
      self skin examination at least once per month. With regards to sun-protective
      behaviour, 85% reported regular sunscreen use and 92% reported regular use of sun
      protective clothing; however, fewer had done this in childhood. CONCLUSIONS:
      Enhanced knowledge of the genetic and environmental risk factors for multiple
      primary melanomas can assist clinicians in assessing risk and planning
      surveillance of patients.

PMID- 21198522
TI  - Dermatophyte infections in Melbourne: Trends from 1961/64 to 2008/09.
AB  - BACKGROUND/OBJECTIVE: To characterise the trends in dermatophyte isolation from
      specimens sourced from metropolitan Melbourne over a 48-year time period. METHOD:
      Analysis of submitted specimens from three time periods. RESULTS: Trends
      identified include: an increasing mean age of the patients; increased numbers of
      onychomycosis isolates; a significant age difference among patients with
      Trichophyton interdigitale isolates compared with patients who had other
      dermatophyte species; and an increasing number of previously rarely isolated
      imported dermatophytes. CONCLUSIONS: Significant shifts are occurring in
      dermatophyte epidemiology.

PMID- 21198523
TI  - Effect of different suture techniques on tension dispersion in cutaneous wounds:
      A pilot study.
AB  - BACKGROUND/OBJECTIVES: Wound tension plays an integral role in both wound healing
      and cosmesis. The use of W-plasty has been shown to evenly distribute tension,
      but is difficult to use in cutaneous surgery. This pilot study aimed to review
      suture techniques that may give the same wound-tension distribution as W-plasty.
      METHODS: Porcine skin mounted on a standard board was used. A standard grid was
      superimposed onto the tissue, and an incision was made which was digitally
      photographed. The defect was then sutured using three suture techniques: simple
      interrupted sutures, mattress sutures and mattress sutures with knots on
      alternate sides. Subcutaneous sutures were also used in conjunction with each of
      these suturing techniques. The grid points were compared and the variation from
      baseline recorded. These variations were then graphed. RESULTS: The simple
      interrupted and mattress sutures showed bias of tension opposite to the side of
      the knot. The alternate mattress suture demonstrated a more even distribution of
      tension. CONCLUSION: The mattress suture with alternating knots had a tension
      pattern that distributed the forces equally across the wound. This is similar to
      the pattern of W-plasty, suggesting the technique may be used for improved wound
      healing and cosmesis in areas of tension.

PMID- 21198524
TI  - Narrowband UVB phototherapy in children: A New Zealand experience.
AB  - BACKGROUND: Phototherapy is effective for many dermatoses in adults, but there is
      a paucity of data for its use in children. OBJECTIVES: To review the efficacy and
      tolerability of narrowband UVB phototherapy in children at a tertiary centre in
      New Zealand, and determine if there were any factors that differentiated
      responders from non-responders. METHODS: A prospective analysis of children (<16
      years old) who had undergone phototherapy over a 15-year period. RESULTS: 116
      children received phototherapy with a total of 144 courses. Mean age was 11.0
      years with the majority being European and having skin phototype II. Atopic
      dermatitis was the most common indication for treatment followed by psoriasis,
      pityriasis lichenoides, nodular prurigo, morphea, vitiligo, urticaria pigmentosa
      and erythropoietic porphyria. Treatment was effective in the majority of children
      (72%). Most received only one course. For responders, the mean number of
      treatments was 32.4. The mean dose per treatment to achieve clearance was 886
      mJ/cm(2) and the mean maximum treatment dose per treatment was 1328 mJ/cm(2) .
      All children tolerated treatment well with 36% developing brief, minimally
      symptomatic, erythema. Only two children experienced exacerbations of their
      underlying dermatoses. CONCLUSIONS: This study shows that phototherapy is an
      effective and well-tolerated treatment modality in children.

PMID- 21198525
TI  - Patients with clinically node negative extremity Merkel cell carcinoma: The
      importance of identifying and treating patients with microscopic nodal
      metastases.
AB  - OBJECTIVES: To review the management of patients with Merkel cell carcinoma (MCC)
      of the distal arm or leg. METHODS: The files of 27 patients with clinically node
      negative extremity-located MCC treated between 1993 and 2007 at Westmead
      Hospital, Sydney, were reviewed. RESULTS: The median age was 79 (range 48-91
      years); there were 16 women and 11 men. The median follow up was 36 months.
      Eighteen patients had a below knee primary and nine had a below elbow primary.
      None had previous treatment of draining nodes. Most (26/27) underwent excision
      and 10 of the 27 received adjuvant local radiotherapy. The median lesion size was
      19 mm (range 10-30 mm). In total 55% relapsed with most occurrences in the
      ipsilateral nodes of the axilla or groin. Median time to relapse was 5.5 months.
      Overall survival at two and five years was 68% and 57%, respectively.
      CONCLUSIONS: Patients with extremity MCC experience a high rate of nodal relapse.
      Recently published evidence supports a survival benefit to identifying patients
      with microscopic nodal metastases. As en bloc primary and nodal treatment is not
      possible, and elective nodal treatment is likely to over-treat many patients,
      sentinel lymph node biopsy is a useful adjunct to current investigations and
      should be recommended.

PMID- 21198526
TI  - Spiral flap for closure of nasal ala defects.
AB  - Despite the existence of numerous methods to close nasal ala defects, many
      produce distortion of the surrounding tissues and obvious scarring. The spiral
      flap produces little or no distortion and well-camouflaged scars. We demonstrate
      these benefits through the presentation of two successful case reports.

PMID- 21198527
TI  - Cutaneous larva migrans in infants in the Adelaide Hills.
AB  - Four infants aged between 8 and 13 months presented between November 2002 and May
      2006 with dermatitis of the lower abdomen, perineum or buttocks. All lived in
      semi-rural properties in the Adelaide Hills and had not travelled outside South
      Australia. Wandering thread-like serpiginous tracks were evident on examination,
      consistent with a diagnosis of cutaneous larva migrans. No abnormalities were
      detected on full blood examination, Strongyloides stercoralis serology or faecal
      analysis. Treatment with oral albendazole resulted in rapid resolution of
      symptoms. An epidemiological survey was undertaken which suggested possums or
      millipedes may have been the source of nematode larvae, the precise nature of
      which is unclear but could include Parastrongyloides trichosuri and Rhabditis
      necromena.

PMID- 21198528
TI  - Type 1 and type IV hypersensitivity to nickel.
AB  - We report a case of type 1 and type IV contact hypersensitivity to nickel. Very
      few cases of immediate contact urticaria to nickel have been reported. The
      mechanism behind this is not fully understood, although it has been postulated
      that nickel may act as a mast cell discharger on a non-immunological basis.
      Nickel is found in varying concentrations in stainless steels; its biological
      availability varies depending on the alloy composition. Our patient has adapted
      her lifestyle to minimize her contact with household appliances containing
      nickel. If medical or dental treatment using stainless steel equipment is
      required, we recommend a short course of oral corticosteroids and antihistamines.

PMID- 21198529
TI  - Mycobacterium abscessus infection complicating a professional tattoo.
AB  - A healthy 23-year-old man presented with a tender papular eruption confined to
      the grey pigment of a recently acquired professional tattoo. Atypical
      mycobacterial infection was suspected and culture of a tissue specimen grew
      Mycobacterium abscessus. He was successfully treated with minocycline and
      subsequently, clarithromycin. We present a brief review of M. abscessus
      infection, with a particular focus on its role in nosocomial infections and in
      the post-tattoo setting.

PMID- 21198531
TI  - Dermoscopy is not always helpful in the diagnosis of vascular lesions.

PMID- 21198532
TI  - Shiny white streaks: An additional dermoscopic finding in melanomas viewed using
      contact polarised dermoscopy.

PMID- 21198534
TI  - Abstracts of the Fertility Society of Australia 29th Annual Scientific Meeting, A
      Healthy Start. October 10-13, 2010. Adelaide, Australia.

PMID- 21198535
TI  - No major role for glutathione S-transferase gene polymorphisms in sensitization
      to para-phenylenediamine and other xenobiotics: a study of association and a meta
      analysis.

PMID- 21198536
TI  - Impaired IFN-alpha secretion by plasmacytoid dendritic cells induced by TLR9
      activation in chronic idiopathic urticaria.
AB  - BACKGROUND: Understanding the early events of the immune response, through the
      activation of plasmacytoid dendritic cells (pDC) by Toll-like receptor (TLR)9
      sensing, could contribute to the evaluation of immune dysregulation in chronic
      idiopathic urticaria (CIU). OBJECTIVES: We decided to investigate innate immunity
      in CIU and the mechanisms implicated in the modulation of interferon (IFN)-alpha
      production by pDC upon TLR9 activation. METHODS: Patients with CIU (n = 31) and
      healthy control subjects (HC, n = 36) were enrolled in the study. Leucocytes
      cultured with the TLR9 ligand, CpG type A, or with inhibitory
      oligodeoxynucleotide (ODN) were used to determine IFN-alpha secretion by enzyme
      linked immunosorbent assay. Enumeration of pDC, intracellular IFN-alpha and
      signal transducers and activators of transcription protein (STAT) (1 and 4)
      phosphorylation were assessed by flow cytometry. TLR9 and regulatory factor-7
      mRNA transcripts were evaluated by real-time polymerase chain reaction. Evidence
      of pDC in the skin lesions of patients was analysed with immunohistochemistry
      staining. RESULTS: The findings show a decreased IFN-alpha secretion induced by
      CpG A by leucocytes, due to the diminished IFN-alpha expression on pDC in CIU. It
      was mediated by TLR9-activation since inhibitory-ODN further suppressed TLR9
      induced IFN-alpha secretion. A normal pDC percentage and degree of activation by
      the expression of costimulatory molecules was observed in CIU, with the rare
      presence of pDC in the skin lesion. In addition, an increased constitutive STAT1
      phosphorylation on nonstimulated lymphocytes and a downregulation of TLR9 mRNA
      transcripts after CpG A activation were verified in patients with CIU.
      CONCLUSIONS: The findings showed an innate immune response in CIU disturbed by
      impairment of the pDC response to TLR9 activation.

PMID- 21198537
TI  - Perturbations of both nonregulatory and regulatory FOXP3+ T cells in patients
      with malignant melanoma.
AB  - BACKGROUND: 'FOXP3+ regulatory T cells' (Tregs) are reported to be increased in
      tumour-bearing hosts including patients with melanoma, leading to tumour immune
      suppression. However, this idea is challenged by recent evidence that the 'FOXP3+
      Treg' fraction in fact contains activated 'nonregulatory' T cells. Also, FOXP3+ T
      cells are reported to have functionally and kinetically distinct subsets.
      OBJECTIVES: To investigate whether either or both of regulatory and
      'nonregulatory' FOXP3+ T cells are perturbed in patients with melanoma. METHODS:
      FOXP3+ T cells were classified into three subsets, namely CD45RO+FOXP3(low)
      nonregulatory T cells, CD45RO+FOXP3(high) effector Tregs, and CD45RO-FOXP3(low)
      naive Tregs, according to their expression levels of FOXP3 and CD45RO. The
      percentage and cytokine production of these FOXP3+ T-cell subsets were assessed
      by flow cytometry. RESULTS: Both regulatory and nonregulatory T cells were
      increased in patients with melanoma. Moreover, we found three unexpected
      perturbations in FOXP3+ T-cell subsets: (i) patients with melanoma showed higher
      frequencies of FOXP3(low) nonregulatory T cells, which decreased and normalized
      after tumour removal; (ii) FOXP3(low) naive Tregs containing higher frequencies
      of interferon-gamma+ cells increased with tumour progression; and (iii)
      CD45RO+FOXP3(high) effector Tregs were pronouncedly infiltrated around tumour
      tissues. CONCLUSIONS: These findings demonstrate that patients with melanoma have
      distinct and differential perturbation of both regulatory and nonregulatory
      FOXP3+ T cells. The degree of perturbation is associated with tumour burden and
      progression, suggesting that the perturbation reflects fundamental
      pathophysiological processes in patients with melanoma. The presented analysis
      provides a practical approach to investigate the immunological environment of
      cancer patients.

PMID- 21198538
TI  - Expression of the soluble vascular endothelial growth factor receptor-1 in
      cutaneous melanoma: role in tumour progression.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF)-A, placenta growth factor
      (PlGF) and their corresponding membrane receptors are involved in autocrine and
      paracrine regulation of melanoma growth and metastasis. Besides the membrane
      receptors, a soluble form of the VEGF receptor (VEGFR)-1 (sVEGFR-1) has been
      identified, that behaves both as a decoy receptor, sequestering VEGF-A and PlGF,
      and as an extracellular matrix (ECM) molecule, promoting endothelial cell
      adhesion and migration through the interaction with alpha5beta1 integrin.
      OBJECTIVES: To analyse whether sVEGFR-1 plays a role during melanoma progression.
      METHODS: sVEGFR-1 expression was evaluated in a panel of 36 melanoma cell lines
      and 11 primary human melanocyte cultures by quantitative real-time polymerase
      chain reaction analysis and in specimens of primary or metastatic melanoma
      lesions from 23 patients by immunohistochemical analysis. RESULTS: sVEGFR-1
      expression was highly upregulated in melanoma cell lines with respect to human
      melanocytes. Interestingly, cell lines obtained from cutaneous metastases showed
      a significant reduction of sVEGFR-1 expression, as compared with cell lines
      derived from primary tumours. These results were confirmed by immunohistochemical
      analysis of sections from primary skin melanomas and the corresponding cutaneous
      metastases, suggesting that modulation of sVEGFR-1 expression influences ECM
      invasion by melanoma cells and metastasis localization. Moreover, we provide
      evidence that adhesion of melanoma cells to sVEGFR-1 is favoured by the
      activation of a VEGF-A/VEGFR-2 autocrine loop. CONCLUSIONS: Our data strongly
      suggest that sVEGFR-1 plays a role in melanoma progression and that low sVEGFR
      1/VEGF-A and sVEGFR-1/transmembrane VEGFR-1 ratios might predict a poor outcome
      in patients with melanoma.

PMID- 21198539
TI  - Photoprotective potential of Cordyceps polysaccharides against ultraviolet B
      radiation-induced DNA damage to human skin cells.
AB  - BACKGROUND: Ultraviolet (UV) radiation causes DNA damage resulting in photoageing
      and skin cancer. UVB (290-320 nm) interacts directly with DNA, inducing two major
      photoproducts: cyclobutane-pyrimidine dimers (CPDs) and (6-4) pyrimidine
      pyrimidone photoproducts. Cordyceps sinensis (Berk.) Sacc. is a medicinal fungus
      with reported anticancer and cytoprotective effects. OBJECTIVES: To investigate
      genoprotective effects of polysaccharide-rich Cordyceps mycelial components
      against UVB-induced damage in normal human fibroblast cells. METHODS: Cultured
      human fibroblasts (BJ cells) were treated for 30 min and, separately, for 24 h
      with hot water extract of Cordyceps fungal mycelia or exopolysaccharides. Cells
      were washed, irradiated with UVB (302 nm), and immediately lysed, after which DNA
      damage, as strand breaks, was measured using an enzyme-assisted comet assay that
      detects CPDs. RESULTS: DNA damage in UVB-irradiated cells was significantly
      lowered (P < 0.01) with Cordyceps pretreatment. Similar results were seen with 30
      min and 24 h pretreatment. Specifically, and in comparison with irradiated cells
      with no Cordyceps pretreatment, there was a 27% reduction in CPDs in irradiated
      cells with 24 h pretreatment with 200 MUg mL(-1) of the hot water Cordyceps
      extract, and a 34% reduction with 24 h pretreatment with 200 MUg mL(-1) of the
      exopolysaccharide extract. CONCLUSIONS: Clear evidence of protection against UVB
      induced CPDs was seen with Cordyceps mycelial extracts. Results indicate that
      Cordyceps may offer photoprotection and lower the risk of basal cell carcinoma,
      the main skin cancer caused by CPDs. Further study is needed to identify
      protective mechanisms.

PMID- 21198540
TI  - Classification of segmental vitiligo on the face: clues for prognosis.
AB  - BACKGROUND: The origin of the distribution of segmental vitiligo (SV) has not yet
      been clearly elucidated. Segmental configurations of cutaneous disorders have
      been explained using two main interpretations, i.e. following either dermatomal
      or blaschkolinear distributions. However, facial SV does not always correspond to
      either of these distributions. OBJECTIVES: We classified facial SV into several
      distinctive subtypes according to specific distributions based on long-term
      observations. METHODS: In total, 257 patients with facial SV were included, all
      of whom were closely observed for more than 1 year. The distribution patterns of
      facial SV were classified according to morphological similarities based on
      clinical observations. RESULTS: The lesions of facial SV were categorized into
      six subtypes: types I-a and I-b, and types II-V. Type I-a and type IV broadly
      involved the mid-level face from the forehead to the lower cheek, but type IV
      lesions selectively appeared on the right side of the face and did not cross the
      midline. Type I-b lesions chiefly involved the forehead and scalp hair. Types II
      and III involved the lower face and, frequently, the neck area, and type V
      lesions were distributed mostly around the right orbital area. The most frequent
      type of lesion in this study was type I-a (28.8%), followed by types II (16.0%),
      III (14.4%), IV (10.9%), I-b (10.5%) and V (8.6%). CONCLUSIONS: Newly established
      patterns of facial SV may be valuable for certain aspects of prognosis, such as
      the likely degree and path of lesion spreading.

PMID- 21198541
TI  - Impact of species variability and 'probe-dependence' on the detection and in vivo
      validation of allosteric modulation at the M4 muscarinic acetylcholine receptor.
AB  - BACKGROUND AND PURPOSE: We recently characterized LY2033298 as a novel allosteric
      modulator and agonist at M(4) muscarinic acetylcholine receptors (mAChRs).
      Evidence also suggested a difference in the potency of LY2033298 at rodent
      relative to human M(4) mAChRs. The current study investigated the basis for the
      species difference of this modulator and used this knowledge to rationalize its
      in vivo actions. EXPERIMENTAL APPROACH: LY2033298 was investigated in vitro in
      CHO cells stably expressing human or mouse M(4) mAChRs, using assays of agonist
      induced ERK1/2 or GSK-3alpha phosphorylation, [(35) S]-GTPgammaS binding, or
      effects on equilibrium binding of [(3) H]-NMS and ACh. The in vivo actions of
      LY2033298 were investigated in a mouse model of amphetamine-induced locomotor
      activity. The function of LY2033298 was examined in combination with ACh,
      oxotremorine or xanomeline. KEY RESULTS: LY2033298 had similar affinities for the
      human and mouse M(4) mAChRs. However, LY2033298 had a lower positive co
      operativity with ACh at the mouse relative to the human M(4) mAChR. At the mouse
      M(4) mAChR, LY2033298 showed higher co-operativity with oxotremorine than with
      ACh or xanomeline. The different degrees of co-operativity between LY2033298 and
      each agonist at the mouse relative to the human M(4) mAChR necessitated the co
      administration of LY2033298 with oxotremorine in order to show in vivo efficacy
      of LY2033298. CONCLUSIONS AND IMPLICATIONS: These results provide evidence for
      species variability when comparing the allosteric interaction between LY2033298
      and ACh at the M(4) mAChR, and also highlight how the interaction between
      LY2033298 and different orthosteric ligands is subject to 'probe dependence'.
      This has implications for the validation of allosteric modulator actions in vivo.

PMID- 21198542
TI  - Tangeretin and its metabolite 4'-hydroxytetramethoxyflavone attenuate EGF
      stimulated cell cycle progression in hepatocytes; role of inhibition at the level
      of mTOR/p70S6K.
AB  - BACKGROUND AND PURPOSE: The mechanisms by which the dietary compound tangeretin
      has anticancer effects may include acting as a prodrug, forming an
      antiproliferative product in cancer cells. Here we show that tangeretin also
      inhibits cell cycle progression in hepatocytes and investigate the role of its
      primary metabolite 4'-hydroxy-5,6,7,8-tetramethoxyflavone (4'-OH-TMF) in this
      effect. EXPERIMENTAL APPROACH: We used epidermal growth factor (EGF)-stimulated
      rat hepatocytes, with [(3)H]-thymidine incorporation into DNA as an index of
      progression to S-phase of the cell cycle, and Western blots for phospho-proteins
      involved in the cell signalling cascade. KEY RESULTS: Incubation of tangeretin
      with microsomes expressing CYP1A, or with hepatocytes, generated a primary
      product we identified as 4'-OH-TMF. Low micromolar concentrations of tangeretin
      or 4'-OH-TMF gave a concentration-dependent inhibition of EGF-stimulated
      progression to S-phase while having little effect on cell viability. To determine
      whether time for conversion of tangeretin to an active metabolite would enhance
      the inhibitory effect we used long pre-incubations; this reduced the inhibitory
      effect, in parallel with a reduction in the concentration of tangeretin. The EGF
      stimulation of hepatocyte cell cycle progression requires signalling through
      Akt/mTOR/p70S6K kinase cascades. The tangeretin metabolite 4'-OH-TMF selectively
      inhibited S6K phosphorylation in the absence of significant inhibition of
      upstream Akt activity, suggesting an effect at the level of mTOR. CONCLUSIONS AND
      IMPLICATIONS: Tangeretin and 4'-OH-TMF both inhibit cell cycle progression in
      primary hepatocytes. The inhibition of p70S6K phosphorylation by 4'-OH-TMF raises
      the possibility that inhibition of the mTOR pathway may contribute to the
      anticancer influence of a flavonoid-rich diet.

PMID- 21198543
TI  - Fenamates as TRP channel blockers: mefenamic acid selectively blocks TRPM3.
AB  - BACKGROUND AND PURPOSE: Fenamates are N-phenyl-substituted anthranilic acid
      derivatives clinically used as non-steroid anti-inflammatory drugs in pain
      treatment. Reports describing fenamates as tools to interfere with cellular
      volume regulation attracted our attention based on our interest in the role of
      the volume-modulated transient receptor potential (TRP) channels TRPM3 and TRPV4.
      EXPERIMENTAL APPROACH: Firstly, we measured the blocking potencies and
      selectivities of fenamates on TRPM3 and TRPV4 as well as TRPC6 and TRPM2 by
      Ca(2+) imaging in the heterologous HEK293 cell system. Secondly, we further
      investigated the effects of mefenamic acid on cytosolic Ca(2+) and on the
      membrane voltage in single HEK293 cells that exogenously express TRPM3. Thirdly,
      in insulin-secreting INS-1E cells, which endogenously express TRPM3, we validated
      the effect of mefenamic acid on cytosolic Ca(2+) and insulin secretion. KEY
      RESULTS: We identified and characterized mefenamic acid as a selective and potent
      TRPM3 blocker, whereas other fenamate structures non-selectively blocked TRPM3,
      TRPV4, TRPC6 and TRPM2. CONCLUSIONS AND IMPLICATIONS: This study reveals that
      mefenamic acid selectively inhibits TRPM3-mediated calcium entry. This
      selectivity was further confirmed using insulin-secreting cells. K(ATP) channel
      dependent increases in cytosolic Ca(2+) and insulin secretion were not blocked by
      mefenamic acid, but the selective stimulation of TRPM3-dependent Ca(2+) entry and
      insulin secretion induced by pregnenolone sulphate were inhibited. However, the
      physiological regulator of TRPM3 in insulin-secreting cells remains to be
      elucidated, as well as the conditions under which the inhibition of TRPM3 can
      impair pancreatic beta-cell function. Our results strongly suggest mefenamic acid
      is the most selective fenamate to interfere with TRPM3 function.

PMID- 21198544
TI  - gamma-Tocotrienol is a novel inhibitor of constitutive and inducible STAT3
      signalling pathway in human hepatocellular carcinoma: potential role as an
      antiproliferative, pro-apoptotic and chemosensitizing agent.
AB  - BACKGROUND AND PURPOSE: Activation of signal transducer and activator of
      transcription 3 (STAT3) play a critical role in the survival, proliferation,
      angiogenesis and chemoresistance of tumour cells. Thus, agents that suppress
      STAT3 phosphorylation have potential as cancer therapies. In the present study,
      we investigated whether the apoptotic, antiproliferative and chemosensitizing
      effects of gamma-tocotrienol are associated with its ability to suppress STAT3
      activation in hepatocellular carcinoma (HCC). EXPERIMENTAL APPROACH: The effect
      of gamma-tocotrienol on STAT3 activation, associated protein kinases and
      phosphatase, STAT3-regulated gene products, cellular proliferation and apoptosis
      in HCC cells was investigated. KEY RESULTS: gamma-Tocotrienol inhibited both the
      constitutive and inducible activation of STAT3 with minimum effect on STAT5.
      gamma-Tocotrienol also inhibited the activation of Src, JAK1 and JAK2 implicated
      in STAT3 activation. Pervanadate reversed the gamma-tocotrienol-induced down
      regulation of STAT3, suggesting the involvement of a protein tyrosine
      phosphatase. Indeed, we found that gamma-tocotrienol induced the expression of
      the tyrosine phosphatase SHP-1 and deletion of the SHP-1 gene by small
      interfering RNA abolished the ability of gamma-tocotrienol to inhibit STAT3
      activation. gamma-Tocotrienol also down-regulated the expression of STAT3
      regulated gene products, including cyclin D1, Bcl-2, Bcl-xL, survivin, Mcl-1 and
      vascular endothelial growth factor. Finally, gamma-tocotrienol inhibited
      proliferation, induced apoptosis and significantly potentiated the apoptotic
      effects of chemotherapeutic drugs (paclitaxel and doxorubicin) used for the
      treatment of HCC. CONCLUSIONS AND IMPLICATIONS: Overall, these results suggest
      that gamma-tocotrienol is a novel blocker of the STAT3 activation pathway, with a
      potential role in future therapies for HCC and other cancers.

PMID- 21198545
TI  - The histone deacetylase inhibitors vorinostat and romidepsin downmodulate IL-10
      expression in cutaneous T-cell lymphoma cells.
AB  - BACKGROUND AND PURPOSE: Vorinostat and romidepsin are histone deacetylase
      inhibitors (HDI), approved for the treatment of cutaneous T-cell lymphoma (CTCL).
      However, the mechanism(s) by which these drugs exert their anti-cancer effects
      are not fully understood. Since CTCL is associated with immune dysregulation, we
      investigated whether these HDI modulated cytokine expression in CTCL cells.
      EXPERIMENTAL APPROACH: CTCL cell lines and primary CTCL cells were treated in
      vitro with vorinostat or romidepsin, or with STAT3 pathway inhibitors. Cell cycle
      parameters and apoptosis were analysed by propidium iodide and annexin
      V/propidium iodide staining respectively. Cytokine expression was analysed using
      QRT-PCR and elisa assays. STAT3 expression/phosphorylation and transcriptional
      activity were analysed using immunoblotting and transfection/reporter assays
      respectively. KEY RESULTS: Vorinostat and romidepsin strongly down-regulated
      expression of the immunosuppressive cytokine, interleukin (IL)-10, frequently
      overexpressed in CTCL, at both the RNA and protein level in CTCL cell lines and
      at the RNA level in primary CTCL cells. Vorinostat and romidepsin also increased
      expression of IFNG RNA and decreased expression of IL-2 and IL-4 RNA, although to
      a lesser extent compared to IL-10. Transient exposure to vorinostat was
      sufficient to suppress IL-10 secretion but was not sufficient to irreversibly
      commit cells to undergo cell death. STAT3 pathway inhibitors decreased production
      of IL-10 and vorinostat/romidepsin partially decreased STAT3-dependent
      transcription without effects on STAT3 expression or phosphorylation. CONCLUSIONS
      AND IMPLICATIONS: These results demonstrate that HDI modulate cytokine expression
      in CTCL cells, potentially via effects on STAT3. Immunomodulation may contribute
      to the clinical activity of HDI in this disease.

PMID- 21198546
TI  - Ectopic overexpression of haem oxygenase-1 protects kidneys from carboplatin
      mediated apoptosis.
AB  - BACKGROUND AND PURPOSE: We previously reported that the activation of the nuclear
      factor of activated T-lymphocyte-3 (NFAT3) by carboplatin leads to renal
      apoptosis as a result of oxidative stress, which is reversed by N-acetylcysteine.
      Herein, we extend our previous work to provide evidence of the molecular
      mechanisms of haem oxygenase (HO)-1 in protecting against injury. EXPERIMENTAL
      APPROACH: Protective mechanisms of HO-1 in carboplatin-mediated renal apoptosis
      were examined in C57BL/6 mice and rat renal tubular cells (RTC) with HO-1
      induction or inactivation/knockdown. KEY RESULTS: The HO-1, induced by cobalt
      protoporphyrin, protected against carboplatin-induced renal injury in vivo. This
      protection was decreased by an inhibitor of HO-1 action, tin protoporphyrin. In
      cultures of RTC, carboplatin-induced apoptosis was similarly affected by HO-1
      overexpression or knockdown. Carboplatin-mediated NFAT3 activation and apoptosis
      involve activation of the signalling kinases, extracellular signal regulated
      kinase, Jun N-terminal kinase and protein kinase C, and such activation was
      reversed in cells overexpressing HO-1. Both products of the HO-1 reaction, CO and
      bilirubin, inhibited (by 30-40%) NFAT3 activation and production of the pro
      apoptotic proteins Bcl-XS/Bax. Additionally, the activation of NFkappaB was
      markedly decreased by HO-1 induction. CONCLUSION AND IMPLICATIONS: HO-1 and its
      reaction products show anti-apoptotic effects in carboplatin-mediated renal
      injury. A novel functional NFAT3 binding site identified in the rat HO-1 promoter
      region was involved in producing a 1.5-fold to 2.5-fold increase in HO-1
      induction by carboplatin. Nevertheless, only HO-1 overexpression and activation
      prior to the carboplatin challenge provided protection against carboplatin
      induced injury.

PMID- 21198547
TI  - Muscarinic receptor antagonists, from folklore to pharmacology; finding drugs
      that actually work in asthma and COPD.
AB  - In the lungs, parasympathetic nerves provide the dominant control of airway
      smooth muscle with release of acetylcholine onto M3 muscarinic receptors.
      Treatment of airway disease with anticholinergic drugs that block muscarinic
      receptors began over 2000 years ago. Pharmacologic data all indicated that
      antimuscarinic drugs should be highly effective in asthma but clinical results
      were mixed. Thus, with the discovery of effective beta-adrenergic receptor
      agonists the use of muscarinic antagonists declined. Lack of effectiveness of
      muscarinic antagonists is due to a variety of factors including unwanted side
      effects (ranging from dry mouth to coma) and the discovery of additional
      muscarinic receptor subtypes in the lungs with sometimes competing effects.
      Perhaps the most important problem is ineffective dosing due to poorly understood
      differences between routes of administration and no effective way of testing
      whether antagonists block receptors stimulated physiologically by acetylcholine.
      Newer muscarinic receptor antagonists are being developed that address the
      problems of side effects and receptor selectivity that appear to be quite
      promising in the treatment of asthma and chronic obstructive pulmonary disease.

PMID- 21198548
TI  - Hydrogen sulphide and angiogenesis: mechanisms and applications.
AB  - In vascular tissues, hydrogen sulphide (H(2)S) is mainly produced from L-cysteine
      by the cystathionine gamma-lyase (CSE) enzyme. Recent studies show that
      administration of H(2)S to endothelial cells in culture stimulates cell
      proliferation, migration and tube formation. In addition, administration of H(2)S
      to chicken chorioallantoic membranes stimulates blood vessel growth and
      branching. Furthermore, in vivo administration of H(2)S to mice stimulates
      angiogenesis, as demonstrated in the Matrigel plug assay. Pathways involved in
      the angiogenic response of H(2)S include the PI-3K/Akt pathway, the mitogen
      activated protein kinase pathway, as well as ATP-sensitive potassium channels.
      Indirect evidence also suggests that the recently demonstrated role of H(2)S as
      an inhibitor of phosphodiesterases may play an additional role in its pro
      angiogenic effect. The endogenous role of H(2)S in the angiogenic response has
      been demonstrated in the chicken chorioallantoic membranes, in endothelial cells
      in vitro and ex vivo. Importantly, the pro-angiogenic effect of vascular
      endothelial growth factor (but not of fibroblast growth factor) involves the
      endogenous production of H(2)S. The pro-angiogenic effects of H(2)S are also
      apparent in vivo: in a model of hindlimb ischaemia-induced angiogenesis, H(2)S
      induces a marked pro-angiogenic response; similarly, in a model of coronary
      ischaemia, H(2)S exerts angiogenic effects. Angiogenesis is crucial in the early
      stage of wound healing. Accordingly, topical administration of H(2)S promotes
      wound healing, whereas genetic ablation of CSE attenuates it. Pharmacological
      modulation of H(2)S-mediated angiogenic pathways may open the door for novel
      therapeutic approaches.

PMID- 21198549
TI  - Peripheral antinociceptive effects of inhibitors of monoacylglycerol lipase in a
      rat model of inflammatory pain.
AB  - BACKGROUND AND PURPOSE The endocannabinoid 2-arachidonoylglycerol (2-AG) is
      degraded primarily by monoacylglycerol lipase (MGL). We compared peripheral
      antinociceptive effects of JZL184, a novel irreversible MGL inhibitor, with the
      reversible MGL-preferring inhibitor URB602 and exogenous 2-AG in rats.
      EXPERIMENTAL APPROACH Nociception in the formalin test was assessed in groups
      receiving dorsal paw injections of vehicle, JZL184 (0.001-300 ug), URB602 (0.001
      600 ug), 2-AG (ED(50)), 2-AG + JZL184 (at their ED(50)), 2-AG + URB602 (at their
      ED(50)), AM251 (80 ug), AM251 + JZL184 (10 ug), AM630 (25 ug) or AM630 + JZL184
      (10 ug). Effects of MGL inhibitors on endocannabinoid accumulation and on
      activities of endocannabinoid-metabolizing enzymes were assessed. KEY RESULTS
      Intra-paw administration of JZL184, URB602 and 2-AG suppressed early and late
      phases of formalin pain. JZL184 and URB602 acted through a common mechanism.
      JZL184 (ED(50) Phase 1: 0.06 +/- 0.028; Phase 2: 0.03 +/- 0.011 ug) produced
      greater antinociception than URB602 (ED(50) Phase 1: 120 +/- 51.3; Phase 2: 66 +/
      23.9 ug) or 2-AG. Both MGL inhibitors produced additive antinociceptive effects
      when combined with 2-AG. Antinociceptive effects of JZL184, like those of URB602,
      were blocked by cannabinoid receptor 1 (CB(1)) and cannabinoid receptor 2 (CB(2))
      antagonists. JZL184 suppressed MGL but not fatty-acid amide hydrolase or N
      arachidonoyl-phosphatidylethanolamine phospholipase D activities ex vivo. URB602
      increased hind paw 2-AG without altering anandamide levels. CONCLUSIONS AND
      IMPLICATIONS MGL inhibitors suppressed formalin-induced pain through peripheral
      CB(1) and CB(2) receptor mechanisms. MGL inhibition increased paw skin 2-AG
      accumulation to mediate these effects. MGL represents a target for the treatment
      of inflammatory pain.

PMID- 21198550
TI  - Dopaminergic mechanisms of reinstatement of MDMA-seeking behaviour in rats.
AB  - BACKGROUND AND PURPOSE: Animal models of drug-seeking suggest that exposure to
      cues associated with self-administered drugs and drug primes might precipitate
      relapse via activation of central dopaminergic substrates. EXPERIMENTAL APPROACH:
      The effects of priming injections of dopamine and 5-HT agonists on drug-seeking
      and effects of dopamine antagonists on methylenedioxymethamphetamine (MDMA)
      produced potentiation of drug-seeking following extinguished MDMA self
      administration were examined. KEY RESULTS: Drug-seeking was produced by exposure
      to a light stimulus that had been paired with self-administered MDMA infusions
      and this effect was potentiated by experimenter-administered injections of the
      dopamine D(2) -like receptor agonist, quinpirole, the indirect agonist,
      amphetamine and the uptake inhibitor, GBR 12909. Drug-seeking was not elicited by
      the dopamine D(1) -like receptor agonist, SKF 81297 or the non-selective agonist,
      apomorphine. The 5-HT receptor agonists DOI or mCPP also failed to elicit drug
      seeking. The 5-HT uptake inhibitor, clomipramine, attenuated drug-seeking
      produced by the MDMA-associated stimulus but failed to alter the potentiated
      response produced by GBR 12909. The D(1) receptor antagonist, SCH 23390 or the
      D(2) receptor antagonist, eticlopride attenuated the potentiation of drug-seeking
      produced by MDMA. CONCLUSIONS AND IMPLICATIONS: These data provide evidence of
      dopaminergic mechanisms in drug-seeking following extinction of MDMA self
      administration. Because tissue levels of 5-HT were significantly decreased
      following MDMA self-administration, we suggest that MDMA begins to preferentially
      activate dopaminergic substrates to potentiate the drug-seeking response.

PMID- 21198551
TI  - Antagonist interaction with the human 5-HT(7) receptor mediates the rapid and
      potent inhibition of non-G-protein-stimulated adenylate cyclase activity: a novel
      GPCR effect.
AB  - BACKGROUND AND PURPOSE: The human 5-hydroxytryptamine(7) (h5-HT(7)) receptor is
      G(s) -coupled and stimulates the production of the intracellular signalling
      molecule cAMP. Previously, we reported a novel property of the h5-HT(7) receptor:
      pseudo-irreversible antagonists irreversibly inhibit forskolin-stimulated (non
      receptor-mediated) cAMP production. Herein, we sought to determine if competitive
      antagonists also affect forskolin-stimulated activity and if this effect is
      common among other G(s) -coupled receptors. EXPERIMENTAL APPROACH: Recombinant
      cell lines expressing h5-HT(7) receptors or other receptors of interest were
      briefly exposed to antagonists; cAMP production was then stimulated by forskolin
      and quantified by an immunocompetitive assay. KEY RESULTS: In human embryonic
      kidney 293 cells stably expressing h5-HT(7) receptors, all competitive
      antagonists inhibited nearly 100% of forskolin-stimulated cAMP production. This
      effect was insensitive to pertussis toxin, that is, not G(i/o) -mediated. Potency
      to inhibit forskolin-stimulated activity strongly correlated with h5-HT(7)
      binding affinity (r(2) = 0.91), indicating that the antagonists acted through h5
      HT(7) receptors to inhibit forskolin. Potency and maximal effects of clozapine, a
      prototypical competitive h5-HT(7) antagonist, were unaffected by varying
      forskolin concentration. Antagonist interaction with h5-HT(6), human beta(1),
      beta(2), and beta(3) adrenoceptors did not inhibit forskolin's activity.
      CONCLUSIONS AND IMPLICATIONS: The inhibition of adenylate cyclase, as measured by
      forskolin's activity, is an underlying property of antagonist interaction with h5
      HT(7) receptors; however, this is not a common property of other G(s) -coupled
      receptors. This phenomenon may be involved in the roles played by h5-HT(7)
      receptors in human physiology. Development of h5-HT(7) antagonists that do not
      elicit this effect would aid in the elucidation of its mechanisms and shed light
      on its possible physiological relevance.

PMID- 21198552
TI  - Kalopanaxsaponin A ameliorates experimental colitis in mice by inhibiting IRAK-1
      activation in the NF-kappaB and MAPK pathways.
AB  - BACKGROUND AND PURPOSE: Kalopanaxsaponin A, a triterpenoid saponin isolated from
      Kalopanax pictus (family Araliaceae), potently inhibited nuclear factor-kappa B
      (NF-kappaB) activation in lipopolysaccharide (LPS)-stimulated peritoneal
      macrophages during a screening programme for anti-colitis agents from natural
      products. Its anti-inflammatory mechanism remains unknown. Therefore, we
      investigated its anti-inflammatory effects in lipopolysaccharide (LPS)- or
      peptidoglycan-stimulated murine peritoneal macrophages and trinitrobenzene
      sulphonic acid (TNBS)-induced colitic mice. EXPERIMENTAL APPROACH: Peritoneal
      macrophages from male ICR mice were stimulated with LPS or peptidoglycan in vitro
      and treated with kalopanaxsaponin A. Colitis was induced in vivo by intrarectal
      administration of TNBS in male ICR mice. Mice were treated daily with
      kalopanaxsaponin A, sulphasalazine or phosphate-buffered saline. Inflammatory
      markers, cytokines, enzymes and transcription factors were measured by ELISA,
      immunoblot, flow cytometry and immunofluorescent confocal microscopy. KEY
      RESULTS: Kalopanaxsaponin A potently inhibited the expression of the pro
      inflammatory cytokines, interleukin (IL)-1beta, tumour necrosis factor (TNF)
      alpha and IL-6, induced by LPS, but not that induced by TNF-alpha, in peritoneal
      macrophages. However, it potently increased the expression of the anti
      inflammatory cytokine IL-10. Kalopanaxsaponin A inhibited activation of the IL-1
      receptor-associated kinase (IRAK)-1, inhibitor of kappaB kinase-beta, NF-kappaB
      and mitogen-activated protein kinases (extracellular signal-regulated kinase, c
      Jun NH(2) -terminal kinase, p-38), but LPS/Toll-like receptor-4 interaction and
      IRAK-4 activation were not affected. Oral administration of kalopanaxsaponin A
      (10 and 20 mg.kg(-1) ) improved the clinical parameters and histology in vivo.
      Kalopanaxsaponin A inhibited NF-kappaB and mitogen-activated protein kinase
      activation induced by TNBS by suppressing IRAK-1 activation. CONCLUSIONS AND
      IMPLICATIONS: Kalopanaxsaponin A may improve inflammatory diseases, such as
      colitis, by inhibiting IRAK-1 activation.

PMID- 21198553
TI  - Therapeutic effect of enhancing endothelial nitric oxide synthase (eNOS)
      expression and preventing eNOS uncoupling.
AB  - Nitric oxide (NO) produced by the endothelium is an important protective molecule
      in the vasculature. It is generated by the enzyme endothelial NO synthase (eNOS).
      Similar to all NOS isoforms, functional eNOS transfers electrons from
      nicotinamide adenine dinucleotide phosphate (NADPH), via the flavins flavin
      adenine dinucleotide and flavin mononucleotide in the carboxy-terminal reductase
      domain, to the heme in the amino-terminal oxygenase domain. Here, the substrate L
      arginine is oxidized to L-citrulline and NO. Cardiovascular risk factors such as
      diabetes mellitus, hypertension, hypercholesterolaemia or cigarette smoking
      reduce bioactive NO. These risk factors lead to an enhanced production of
      reactive oxygen species (ROS) in the vessel wall. NADPH oxidases represent major
      sources of this ROS and have been found upregulated in the presence of
      cardiovascular risk factors. NADPH-oxidase-derived superoxide avidly reacts with
      eNOS-derived NO to form peroxynitrite (ONOO(-)). The essential NOS cofactor (6R
      )5,6,7,8-tetrahydrobiopterin (BH(4) ) is highly sensitive to oxidation by this
      ONOO(-). In BH(4) deficiency, oxygen reduction uncouples from NO synthesis,
      thereby converting NOS to a superoxide-producing enzyme. Among conventional
      drugs, compounds interfering with the renin-angiotensin-aldosterone system and
      statins can reduce vascular oxidative stress and increase bioactive NO. In recent
      years, we have identified a number of small molecules that have the potential to
      prevent eNOS uncoupling and, at the same time, enhance eNOS expression. These
      include the protein kinase C inhibitor midostaurin, the pentacyclic triterpenoids
      ursolic acid and betulinic acid, the eNOS enhancing compounds AVE9488 and
      AVE3085, and the polyphenolic phytoalexin trans-resveratrol. Such compounds
      enhance NO production from eNOS also under pathophysiological conditions and may
      thus have therapeutic potential.

PMID- 21198554
TI  - Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human
      embryonic stem cells during multilineage differentiation.
AB  - BACKGROUND AND PURPOSE: Teratogenic substances induce adverse effects during the
      development of the embryo. Multilineage differentiation of human embryonic stem
      cells (hESCs) mimics the development of the embryo in vitro. Here, we propose a
      transcriptomic approach in hESCs for monitoring specific toxic effects of
      compounds as an alternative to traditional time-consuming and cost-intensive in
      vivo tests requiring large numbers of animals. This study was undertaken to
      explore the adverse effects of cytosine arabinoside (Ara-C) on randomly
      differentiated hESCs. EXPERIMENTAL APPROACH: Human embryonic stem cells were used
      to investigate the effects of a developmental toxicant Ara-C. Sublethal
      concentrations of Ara-C were given for two time points, day 7 and day 14 during
      the differentiation. Gene expression was assessed with microarrays to determine
      the dysregulated transcripts in presence of Ara-C. KEY RESULTS: Randomly
      differentiated hESCs were able to generate the multilineage markers. The low
      concentration of Ara-C (1 nM) induced the ectoderm and inhibited the mesoderm at
      day 14. The induction of ectodermal markers such as MAP2, TUBB III, PAX6, TH and
      NESTIN was observed with an inhibition of mesodermal markers such as HAND2,
      PITX2, GATA5, MYL4, TNNT2, COL1A1 and COL1A2. In addition, no induction of
      apoptosis was observed. Gene ontology revealed unique dysregulated biological
      process related to neuronal differentiation and mesoderm development. Pathway
      analysis showed the axon guidance pathway to be dysregulated. CONCLUSIONS AND
      IMPLICATIONS: Our results suggest that hESCs in combination with toxicogenomics
      offer a sensitive in vitro developmental toxicity model as an alternative to
      traditional animal experiments.

PMID- 21198555
TI  - Cough: an unmet clinical need.
AB  - Cough is among the most common complaints for which patients worldwide seek
      medical attention. Thus, the evaluation and treatment of cough result in
      tremendous financial expenditure and consumption of health care resources. Yet,
      despite the clinical significance of cough, research efforts aimed at improving
      diagnostic capabilities and developing more effective therapeutic agents have
      been, to date, disappointing in their limited scope and outcomes. Acute cough due
      to the common cold represents the most common type of cough. Currently, available
      medications for the symptomatic management of acute cough are inadequate due to
      lack of proven efficacy and/or their association with undesirable or intolerable
      side effects at anti-tussive doses. Subacute cough, often representing a
      prolonged post-viral response, is typically refractory to standard anti-tussive
      therapy. Few clinical trials have evaluated therapeutic options for subacute
      cough. Diagnostic challenges facing the clinician in the management of chronic
      cough include the determination of whether symptoms of upper airway cough
      syndrome (formerly, postnasal drip syndrome) or gastro-oesophageal reflux disease
      are indeed the underlying cause of cough. Chronic, refractory unexplained
      (formerly, idiopathic) cough must be distinguished from cough that has not been
      fully evaluated and treated according to current guideline recommendations.
      Eagerly awaited are new safe and effective anti-tussive agents for use when cough
      suppression is desired, regardless of underlying aetiology of cough, as well as
      practical, validated ambulatory cough counters to aid clinical assessment and
      future research in the field of cough.

PMID- 21198557
TI  - Investigation of widespread neocortical pathology associated with hippocampal
      sclerosis in epilepsy: a postmortem study.
AB  - PURPOSE: One possible cause for surgical failure following temporal lobectomy for
      the treatment of epilepsy due to classical hippocampal sclerosis (CHS) is the
      presence of more widespread cortical changes. Neocortical changes in CHS shown by
      quantitative neuroimaging studies may involve hippocampal projection pathways.
      Our aim was to quantitate neocortical pathology using a postmortem series of
      brains from patients with epilepsy and CHS. METHODS: Sections from 13 cortical
      regions from both left and right hemispheres, including hippocampal projection
      pathways, were examined from nine epilepsy patients with unilateral CHS (4),
      bilateral CHS (2), non-CHS (3), and non-epilepsy controls (4). Using GFAP, CD68,
      and NPY immunohistochemistry as markers of acquired neocortical pathology,
      quantitative analysis of the staining fractions in the cortex and white matter
      was carried out. KEY FINDINGS: Higher staining fractions were observed for all
      markers in both cortex and white matter in CHS patients, which was significantly
      different for CD68 and NPY compared to controls (p < 0.05) but not to non-CHS
      epilepsy cases. There was no significant difference between staining fractions in
      left and right hemispheres for unilateral CHS cases. Regional analysis showed
      preferential gliosis and microgliosis of temporal poles, frontal poles, and
      orbitofrontal cortex in epilepsy cases. SIGNIFICANCE: This study supports
      acquired neocortical pathology in epilepsy patients both with and without CHS.
      Cortical pathology does not show lateralization to the side of CHS. Preferential
      involvement of the temporal and frontal poles may relate to other factors, such
      as cortical injury associated with seizures, rather than involvement through
      hippocampal pathways.

PMID- 21198558
TI  - Cortical curvature analysis in MRI-negative temporal lobe epilepsy: a surrogate
      marker for malformations of cortical development.
AB  - PURPOSE: To investigate cerebral cortical surface morphology in a magnetic
      resonance (MRI)-negative temporal lobe epilepsy (TLE) cohort, and to
      differentiate between the effects on cortical morphology of cerebral volume loss
      associated with TLE, and abnormalities suggestive of malformations of cortical
      development (MCDs). METHODS: MRI data was gathered for 29 MRI-negative patients
      and 40 neurologically normal controls. Automated methods of surface
      reconstruction were applied to all MRI data for the purposes of localized
      analysis of cortical curvature. As an adjunct to this analysis, measures of whole
      brain gray and white matter volumes, as well as cortical thickness, were also
      generated to determine the degree of whole-brain volume loss in TLE, and its
      impact on cortical morphology. RESULTS: Automated analysis of the average
      cortical surface of the patient group revealed an area of abnormal cortical
      curvature in the basal left temporal lobe. The presence of whole-brain volume
      loss in TLE was confirmed and found not to contribute to the cortical curvature
      abnormality in the temporal lobe. These results support the hypothesis that
      cortical curvature abnormalities in TLE may be indicative of a subtle MCD.
      DISCUSSION: Subtle MCDs such as abnormal indices of curvature may be associated
      with partial epilepsy. Analysis of these parameters may increase the diagnostic
      yield from MRI.

PMID- 21198556
TI  - Glucocorticosteroids: current and future directions.
AB  - Glucocorticoids are the most effective anti-inflammatory therapy for asthma yet
      are relatively ineffective in chronic obstructive pulmonary disease.
      Glucocorticoids suppress inflammation via several molecular mechanisms.
      Glucocorticoids suppress the multiple inflammatory genes that are activated in
      chronic inflammatory diseases, such as asthma, by reversing histone acetylation
      of activated inflammatory genes through binding of ligand-bound glucocorticoid
      receptors (GR) to co-activator molecules and recruitment of histone deacetylase-2
      to the activated inflammatory gene transcription complex (trans-repression). At
      higher concentrations of glucocorticoids GR homodimers interact with DNA
      recognition sites to activate transcription through increased histone acetylation
      of anti-inflammatory genes and transcription of several genes linked to
      glucocorticoid side effects (trans-activation). Glucocorticoids also have post
      transcriptional effects and decrease stability of some pro-inflammatory mRNA
      species. Decreased glucocorticoid responsiveness is found in patients with severe
      asthma and asthmatics who smoke, as well as in all patients with chronic
      obstructive pulmonary disease. Several molecular mechanisms of glucocorticoid
      resistance have now been identified which involve post-translational
      modifications of GR. Histone deacetylase-2 is markedly reduced in activity and
      expression as a result of oxidative/nitrative stress so that inflammation becomes
      resistant to the anti-inflammatory actions of glucocorticoids. Dissociated
      glucocorticoids and selective GR modulators which show improved trans-repression
      over trans-activation effects have been developed to reduce side effects, but so
      far it has been difficult to dissociate anti-inflammatory effects from adverse
      effects. In patients with glucocorticoid resistance alternative anti-inflammatory
      treatments are being investigated as well as drugs that may reverse the molecular
      mechanisms of glucocorticoid resistance.

PMID- 21198559
TI  - Circulating endothelial-coagulative activation markers after smoking cessation: a
      12-month observational study.
AB  - BACKGROUND: Cigarette smoking is associated with cardiovascular morbidity and
      mortality. Exposure to cigarette smoke can cause endothelial dysfunction with
      impaired endothelium-dependent vasodilation and 'endothelial activation', which
      predispose to atherothrombosis. The effects of continued smoking and smoking
      cessation on the level of endothelial, platelet and clotting activation have not
      been described previously. Here, we prospectively monitored changes in
      circulating endothelial-coagulative activation markers in smokers undertaking
      smoking cessation. METHOD: This 12-month prospective study of 174 smokers with no
      commonly acquired atherothrombotic risk factors underwent an intensive smoking
      cessation programme investigating the effect of quitting on circulating levels of
      von Willebrand's Factor Antigen (vWF:Ag), soluble Thrombomodulin (sTM), d-Dimer
      (d-D), prothrombin fragment F1+2 (F1+2), platelet factor-4 (PF4) and beta
      Thromboglobulin (beta-TG). Blood samples and study measures were collected and
      compared at baseline and at 2, 6 and 12months after smoking cessation from
      quitters and relapsers'. RESULTS: No significant differences in demographic or
      laboratory parameters at baseline were observed between the study groups.
      Significant changes in von Willebrand's Factor activity were observed at 2months
      after smoking cessation, with levels decreasing from 141.8% to 113.6%.
      Substantial modifications in d-Dimer, prothrombin fragment F1 +2, platelet factor
      4 and beta-thromboglobulin concentrations were observed only at 6 and 12months
      after smoking cessation. Positive associations between baseline levels of these
      biomarkers and number of pack per years have been demonstrated. CONCLUSIONS:
      Chronic exposure to cigarette smoke sustains the activation of the endothelial
      coagulative system and abstinence may result in the improvement of several
      endothelial-coagulative abnormalities in regular smokers. This may translate into
      an overall decline in cardiovascular risk.

PMID- 21198560
TI  - Randomized placebo controlled trial of furosemide on subjective perception of
      dyspnoea in patients with pulmonary oedema because of hypertensive crisis.
AB  - BACKGROUND: To compare the administration of furosemide with placebo on the
      subjective perception of dyspnoea in patients with acute pulmonary oedema because
      of hypertensive crisis. Design  Randomized, controlled and double-blinded
      clinical trial. SETTING: Municipal emergency medical service system and
      university-based emergency department. PARTICIPANTS: Fifty-nine patients with
      pulmonary oedema because of hypertensive crisis. INTERVENTIONS: Additional to
      administration of oxygen, morphine-hydrochloride and urapidil until the systolic
      blood pressure was below 160mmHg, the patients were randomized to receive
      furosemide 80mg IV bolus (furosemide group) or saline placebo (placebo group).
      MAIN OUTCOME MEASURES: The primary outcome was the subjective perception of
      dyspnoea as measured with a modified BORG scale at one hour after randomization.
      Secondary outcome parameters were the subjective perception of dyspnoea of
      patients as measured with a modified BORG scale and a visual analogue scale at 2,
      3 and 6h after randomization of the patient; course of the systolic arterial
      pressure and peripheral oxygen saturation and lactate at admission and at 6h
      after admission. RESULTS: In 25 patients in the furosemide group and in 28
      patients in the placebo group, a BORG score could be obtained. There was no
      statistically significant difference in the severity of dyspnoea at one hour
      after randomization (P=0.40). The median BORG score at 1h after randomization in
      the furosemide group was 3 (IQR 2 to 4) compared to 3 (IQR 2 to 7) in the placebo
      group (P=0.40). Those patients who were randomized to the placebo group needed
      higher doses of urapidil at 20min after randomization. There were no significant
      differences in the rate of adverse events, nonfatal cardiac arrests or death
      between the two groups. CONCLUSIONS: The subjective perception of dyspnoea in
      patients with hypertensive pulmonary oedema was not influenced by the application
      of a loop-diuretic. Therefore, additional furosemide therapy needs to be
      scrutinized in the therapy of these patients.

PMID- 21198561
TI  - Genetics of type 2 diabetes: pathophysiologic and clinical relevance.
AB  - BACKGROUND: Recent genome-wide association studies enlarged our knowledge about
      the genetic background of type 2 diabetes. AIMS: This review provides an overview
      of the role of these novel genetic findings for the pathophysiology, prediction
      and treatment of type 2 diabetes. RESULTS: The genetic susceptibility to type 2
      diabetes appears to be determined by many common variants in multiple gene loci
      with low effect sizes. Although at least 36 diabetes-associated genes were
      identified, only about 10% of the heritability of type 2 diabetes can be
      explained. Most of the discovered gene variants have been linked to beta-cell
      dysfunction rather than insulin resistance, which might challenge established
      thinking of type 2 diabetes as a predominant disorder of insulin action. Genetic
      data can lead to statistically significant, but not to clinically relevant
      contributions to risk prediction for type 2 diabetes. Nevertheless, preliminary
      evidence suggests interactions between genotypes and response to lifestyle
      changes or drug treatment. CONCLUSIONS: Future studies need to target the issue
      of hidden heritability and to detect the causal gene variants within the
      identified gene loci. Improved understanding of the genetic contribution to type
      2 diabetes may then help addressing the questions whether genotyping is useful to
      predict individual diabetes risk, identifies individual responsiveness to
      preventive and therapeutic interventions or at least allows for breaking down
      type 2 diabetes into smaller, clinically meaningful subtypes.

PMID- 21198562
TI  - The associations between headaches and psychopathology: a survey in school
      children.
AB  - BACKGROUND: Headaches are common in childhood and significantly impact children's
      quality of life. On the contrary to the adolescent and adult population, there
      are few data on the associations between headaches and psychopathology in young
      children. OBJECTIVE: The aim of this study was to examine the relationships
      between child headaches, emotional and behavioral difficulties in children aged 6
      11 years old. METHODS: A cross-sectional survey was conducted in 2004 in 100
      primary schools from a large French region, with 2341 children aged 6-11 years
      old randomly selected. Child headache status, comorbid physical conditions, and
      socioeconomic characteristics were collected in parent-administered
      questionnaires. Child psychopathology outcomes were assessed using child- and
      parent-reported standardized instruments: respectively, the Dominic Interactive
      and the Strengths and the Difficulties Questionnaire. Associations were estimated
      using logistic regression models. RESULTS: Response rates to the parent
      questionnaire and the Dominic Interactive were 57.4% and 95.1%, respectively. The
      final sample size was 1308 children. Eleven percent of the children already
      experienced frequent headaches in their lifetime, with no difference by age or
      gender. Headaches were associated with parent-reported emotional problems
      (OR=1.76; 95% CI: 1.03-3.01) and self-reported general anxiety disorder (OR=1.99;
      1.13-3.52). Comorbid physical conditions >=2 appeared as an independent factor
      significantly associated with headaches (OR =1.75; 95% CI: 1.13-2.73). Inversely,
      low parental punitive behaviors were less frequently associated with headaches
      (OR=0.41; 95% CI: 0.18-0.94). CONCLUSION: Our results suggest some associations
      between headaches, emotional disorders, and comorbid physical conditions in young
      children aged 6-11 years old. Those results should be considered in the treatment
      approaches of childhood headaches and from the etiological aspect.

PMID- 21198563
TI  - Multifocal nummular headache with trophic changes.

PMID- 21198565
TI  - Transcranial magnetic stimulation.

PMID- 21198566
TI  - The effect of prophylactic medications on TMS for migraine aura.
AB  - PURPOSE: Low frequency transcranial magnetic stimulation (TMS) has recently been
      shown to be effective for the acute treatment of migraine with aura. TMS has
      recently been shown to inhibit cortical spreading depression (CSD). Prophylactic
      medications (PM) may reduce the frequency of migraine attacks by elevating CSD
      threshold. The interaction between PM and TMS is unknown. METHODS: Subgroup
      analysis was performed on a double-blind, Sham-controlled study that evaluated
      the efficacy and safety of TMS for the acute treatment of migraine with aura.
      Analysis of the primary efficacy endpoint pain-free at 2 hours (pain-free rate
      [PFR]) between TMS and Sham groups was performed based on the non-randomized use
      of PM. RESULTS: A total of 164 subjects eligibly treated at least 1 migraine with
      aura attack with TMS (n = 82) or Sham stimulation (n=82). Baseline pain intensity
      at the time of treatment for the first attack was no pain (31%), mild (40%),
      moderate (23%), or severe pain (6%). PM were used by 37% (31/82) and 41.5%
      (34/82) in the Sham- and TMS-treated patients, respectively. Sham patients on no
      PM (Sham without) had significantly higher PFR than Sham-treated patients on PM
      (Sham with) (P = .0014). There was no difference in PFR between TMS-treated
      patients on (TMS with) or off (TMS without) PM (P = .5513). However, TMS with had
      significantly higher PFR than Sham with patients (P= .002). There was no
      difference in PFR between TMS without and Sham without patients (P = .4061).
      CONCLUSION: Prophylactic medications do not appear to influence the treatment
      response to TMS. The better response in Sham-treated patients not on PM may
      indicate a more responsive subgroup or different patient phenotype than those
      currently using PM. These findings will need to be verified in a larger patient
      sample randomized by presence or absence of PM.

PMID- 21198567
TI  - Non-steroidal anti-inflammatory drugs (NSAIDs) for acute migraine treatment.

PMID- 21198568
TI  - Commentary from the Refractory Headache Special Interest Section on defining the
      pharmacologically intractable headache for clinical trials and clinical practice.

PMID- 21198571
TI  - Key concepts of migraine postdrome: a qualitative study to develop a post
      migraine questionnaire.
AB  - OBJECTIVE: To understand migraine postdrome by directly interviewing migraine
      patients with postdrome symptoms. To document these symptoms, as well as impacts,
      as a prelude to developing a postdrome migraine questionnaire. BACKGROUND:
      Migraine attacks are traditionally divided into 4 phases. Of these, the postdrome
      is the least studied, and no patient-reported outcomes to assess symptoms and
      impacts of this migraine phase have been published. METHODS: Qualitative concept
      elicitation focus groups were conducted with 34 patients in 3 geographically
      diverse US cities to elicit the symptoms and burden of migraine postdrome. Data
      elicited from focus groups were coded using Atlas.ti software to facilitate
      identification of concepts and terminologies of migraine postdrome. A draft
      questionnaire was developed based on the symptoms and impacts of migraine
      postdrome described by patients. Cognitive debriefing interviews were conducted
      with 15 patients in Connecticut and Chicago to confirm content validity,
      relevance, and comprehension. RESULTS: Patients defined the onset of postdrome as
      when they no longer experienced the migraine pain. Postdrome was often described
      as "[being] or [feeling] wiped out" and "headache hangover." The symptoms most
      frequently reported by the patients who participated in the focus groups and
      included in the draft post-migraine questionnaire were: tiredness, difficulty
      concentrating, weakness, dizziness, lightheadedness, and decreased energy.
      Patients also reported decreased activity level as a result of experiencing
      postdrome symptoms. Postdrome symptoms were reported to impact the ability to
      work, to affect family interactions and social life, and to cause cognitive
      impairment. A preliminary questionnaire measuring severity and duration of
      symptoms and severity of impacts of the post-migraine experience, with an 11
      point (0 to 10) response scale, was developed. This preliminary questionnaire was
      tested for content validity, relevance, and comprehension using cognitive
      debriefing interviews. All patients reported that the questionnaire was relevant
      to their condition. Irrelevant and redundant items such as body tension and
      annoyance were eliminated. CONCLUSIONS: Migraine postdrome is debilitating for
      those who experience it. Concept elicitation and cognitive debriefing research
      support the relevance of the items in the post-migraine questionnaire. Future
      research will provide evidence of the post-migraine questionnaire's psychometric
      properties and interpretation guidelines.

PMID- 21198572
TI  - Occipital neuralgia with and without migraine: difference in pain characteristics
      and risk factors.
AB  - OBJECTIVES: We conducted this study to identify differences in presentation and
      symptomatology between patients with isolated occipital neuralgia (ON) and
      patients with ON who also had migraine headache (ON + M). BACKGROUND: Occipital
      neuralgia is an uncommon cause of headaches. Very little is known about the pain
      characteristics and associated features of patients with ON + M and whether these
      pain characteristics differ from those of patients with isolated ON. METHODS: We
      studied 35 consecutive patients presenting with ON to the University of Southern
      California headache clinic. All patients met International Headache Society
      criteria for diagnosis of ON. Patients completed a questionnaire designed for
      this study. We also collected demographic data, including age, gender, and
      ethnicity. RESULTS: Twenty patients had ON + M and 15 had isolated ON. There was
      no difference in age, gender or ethnicity between patients with ON + M and those
      with isolated ON. Patients with ON + M had significantly more complaints of pain
      traveling to the scalp and presence of scalp tenderness and tingling compared
      with patients with isolated ON; 25% patients in the ON + M group described the
      pain as "dull" whereas none of the isolated ON group reported this
      characteristic. There was higher use of chiropractors and massage therapy in
      patients from ON + M group than from isolated ON. CONCLUSION: There may be
      significant differences in pain characteristics for patients with ON + M and
      those for patients with isolated ON. The data indicate that patients with
      migraine should also be screened for symptoms of ON, as there may be similarities
      in presentation. The clinical implications of distinguishing ON + M and isolated
      ON include differences in treatment regimen, avoidance of inappropriate use of
      medical resources, and differences in long-term outcomes.

PMID- 21198573
TI  - Frovatriptan for prophylactic treatment of cluster headache: lessons for future
      trial design.
AB  - OBJECTIVE: The aim of this study was to determine whether frovatriptan would show
      efficacy in short term prophylactic treatment of episodic cluster headache (ECH)
      in comparison to placebo. BACKGROUND: The 5-hydroxytryptamine(1B/d) (5-HT(1B/d) )
      agonists naratriptan, eletriptan, and frovatriptan have been shown to reduce the
      frequency of ECH. So far, no double-blind placebo-controlled trials have
      investigated the potential prophylactic effects of 5-HT(1B/d) -agonists in ECH.
      METHODS: The trial was conducted as a multi-center, placebo-controlled,
      randomized, double-blind, prospective phase III parallel-group trial with two
      independent treatment groups (5 mg frovatriptan vs placebo). It was planned to
      randomize about 96 patients (48 patients per group) into the trial to obtain 80
      evaluable patients (40 patients per group). RESULTS: The study was prematurely
      discontinued after 13 months and enrollment of 11, instead of the planned 80
      patients, by the sponsor due to infeasibility. Recruitment was slow and each of
      the patients included conducted major protocol violations. The differences in the
      primary and secondary endpoints were not significant. CONCLUSION: This study
      shows that particular therapeutic aims are impossible to be addressed in a double
      blind, randomized, parallel group, study design with specific inclusion and
      exclusion criteria according to the International Headache Society (IHS)
      guidelines for controlled trials of drugs in cluster headache. Further studies
      are required to evaluate the potential efficacy of triptans in the prophylactic
      treatment of ECH. The outcome of the trial suggests that the recommendations of
      the Guidelines for controlled Trials of Drugs in Cluster Headache from the IHS
      should be revised.

PMID- 21198574
TI  - "Mixing triptans": patient satisfaction.
AB  - BACKGROUND: Although some patients may prefer using an oral triptan other than
      sumatriptan and injectable sumatriptan to treat an attack of persistent migraine,
      administration of 2 different triptans within a 24-hour period currently is
      contradicted. OBJECTIVE: We sought to determine patient satisfaction with an
      acute migraine treatment regimen wherein patients were permitted to administer an
      oral triptan other than sumatriptan and injectable sumatriptan within 24 hours of
      one another METHODS: We evaluated a consecutive series of migraine patients who
      either had tried and failed oral sumatriptan or were using another oral triptan
      and were satisfied with it. We advised subjects that they could administer their
      oral triptan and injectable sumatriptan within a single 24-hour period (but not
      within 2 hours of one another); we termed such treatment "mixing triptans." We
      asked all subjects to keep detailed written headache diaries for the 6-month
      treatment period, and at the 6-month end-of-study visit we asked subjects who had
      treated at least 3 migraine attacks by mixing triptans to rate their satisfaction
      with that treatment according to a 5-point Likert scale. RESULTS: Of the 200
      subjects enrolled, 132 (66%) used an oral triptan other than sumatriptan and
      injectable sumatriptan within a 24-hour period on at least 3 occasions. At their
      final follow-up visits, 117 (89%) of the 132 reported themselves "very satisfied"
      or "satisfied" with this specific treatment regimen. No serious adverse events
      were recorded. CONCLUSION: The option of sequentially using an oral triptan other
      than sumatriptan and injectable sumatriptan to treat a given attack of migraine
      appears to correlate with a high rate of patient satisfaction. While in our
      subject population this treatment regimen was well tolerated, our study results
      do not suffice to establish the safety of "mixing triptans."

PMID- 21198575
TI  - Membership survey: use of oral triptans and injectable sumatriptan within the
      same 24-hour period.

PMID- 21198576
TI  - The challenge of new daily persistent headache.
AB  - New daily persistent headache is a rare chronic daily headache of long duration
      characterized by the abrupt onset of persistent headache that generally develops
      over less than 3 days and does not remit. While it was initially thought to be a
      benign, self-limiting disorder, further research has shown that a significant
      percentage of patients continue to suffer for many years, often experiencing pain
      that is refractory to treatment. This article reviews the symptoms,
      pathophysiology, diagnostic criteria, diagnostic testing, treatment, and
      prognosis.

PMID- 21198577
TI  - Treatment of migraine with occipital nerve blocks using only corticosteroids.
AB  - The indications for using steroids when performing occipital nerve blocks (ONBs)
      are not completely clear. We report a patient with chronic migraines who was
      allergic to local anesthetics, for whom ONBs using only corticosteroid proved
      useful. To our knowledge, this is only published case describing the effects of
      ONBs using only corticosteroid, without local anesthetic.

PMID- 21198578
TI  - A critical appraisal of the clinical trial on spinal manipulative therapy (SMT)
      and pediatric cervicogenic headache.

PMID- 21198581
TI  - 2010: year in review.
AB  - This section of Headache annually reviews the status of recently completed and
      ongoing clinical trials involving headache disorders. The review will focus on
      multicenter trials of new therapies as well as novel formulations of previously
      approved therapeutics. Table 1 summarizes major migraine therapeutic trials that
      have been completed recently, according to data obtained from the
      "ClinicalTrials.Gov" website as well as from corporate press releases. Table 2
      summarizes the major therapeutic trials that are ongoing at the present time.

PMID- 21198584
TI  - State-level health policy research: looking back, looking ahead.

PMID- 21198586
TI  - Abstracts of the Annual Congress of the British Society for Immunology. December
      6-10, 2010. Liverpool, United Kingdom.

PMID- 21198585
TI  - Harvesting the lessons of state health policy.

PMID- 21198587
TI  - Aquatic adaptations in the nose of carnivorans: evidence from the turbinates.
AB  - Inside the mammalian nose lies a labyrinth of bony plates covered in epithelium
      collectively known as turbinates. Respiratory turbinates lie anteriorly and aid
      in heat and water conservation, while more posterior olfactory turbinates
      function in olfaction. Previous observations on a few carnivorans revealed that
      aquatic species have relatively large, complex respiratory turbinates and greatly
      reduced olfactory turbinates compared with terrestrial species. Body heat is lost
      more quickly in water than air and increased respiratory surface area likely
      evolved to minimize heat loss. At the same time, olfactory surface area probably
      diminished due to a decreased reliance on olfaction when foraging under water. To
      explore how widespread these adaptations are, we documented scaling of
      respiratory and olfactory turbinate surface area with body size in a variety of
      terrestrial, freshwater, and marine carnivorans, including pinnipeds, mustelids,
      ursids, and procyonids. Surface areas were estimated from high-resolution CT
      scans of dry skulls, a novel approach that enabled a greater sampling of taxa
      than is practical with fresh heads. Total turbinate, respiratory, and olfactory
      surface areas correlate well with body size (r(2) >=0.7), and are relatively
      smaller in larger species. Relative to body mass or skull length, aquatic species
      have significantly less olfactory surface area than terrestrial species.
      Furthermore, the ratio of olfactory to respiratory surface area is associated
      with habitat. Using phylogenetic comparative methods, we found strong support for
      convergence on 1:3 proportions in aquatic taxa and near the inverse in
      terrestrial taxa, indicating that aquatic mustelids and pinnipeds independently
      acquired similar proportions of olfactory to respiratory turbinates. Constraints
      on turbinate surface area in the nasal chamber may result in a trade-off between
      respiratory and olfactory function in aquatic mammals.

PMID- 21198589
TI  - Ice-cover effects on competitive interactions between two fish species.
AB  - 1. Variations in the strength of ecological interactions between seasons have
      received little attention, despite an increased focus on climate alterations on
      ecosystems. Particularly, the winter situation is often neglected when studying
      competitive interactions. In northern temperate freshwaters, winter implies low
      temperatures and reduced food availability, but also strong reduction in ambient
      light because of ice and snow cover. Here, we study how brown trout [Salmo trutta
      (L.)] respond to variations in ice-cover duration and competition with Arctic
      charr [Salvelinus alpinus (L.)], by linking laboratory-derived physiological
      performance and field data on variation in abundance among and within natural
      brown trout populations. 2. Both Arctic charr and brown trout reduced resting
      metabolic rate under simulated ice-cover (darkness) in the laboratory, compared
      to no ice (6-h daylight). However, in contrast to brown trout, Arctic charr was
      able to obtain positive growth rate in darkness and had higher food intake in
      tank experiments than brown trout. Arctic charr also performed better (lower
      energy loss) under simulated ice-cover in a semi-natural environment with natural
      food supply. 3. When comparing brown trout biomass across 190 Norwegian lakes
      along a climate gradient, longer ice-covered duration decreased the biomass only
      in lakes where brown trout lived together with Arctic charr. We were not able to
      detect any effect of ice-cover on brown trout biomass in lakes where brown trout
      was the only fish species. 4. Similarly, a 25-year time series from a lake with
      both brown trout and Arctic charr showed that brown trout population growth rate
      depended on the interaction between ice breakup date and Arctic charr abundance.
      High charr abundance was correlated with low trout population growth rate only in
      combination with long winters. 5. In conclusion, the two species differed in
      performance under ice, and the observed outcome of competition in natural
      populations was strongly dependent on duration of the ice-covered period. Our
      study shows that changes in ice phenology may alter species interactions in
      Northern aquatic systems. Increased knowledge of how adaptations to winter
      conditions differ among coexisting species is therefore vital for our
      understanding of ecological impacts of climate change.

PMID- 21198590
TI  - Predicting the post-fire responses of animal assemblages: testing a trait-based
      approach using spiders.
AB  - 1. Developing a predictive understanding of how species assemblages respond to
      fire is a key conservation goal. In moving from solely describing patterns
      following fire to predicting changes, plant ecologists have successfully
      elucidated generalizations based on functional traits. Using species traits might
      also allow better predictions for fauna, but there are few empirical tests of
      this approach. 2. We examined whether species traits changed with post-fire age
      for spiders in 27 sites, representing a chronosequence of 0-20 years post-fire.
      We predicted a priori whether spiders with ten traits associated with survival,
      dispersal, reproduction, resource-utilization and microhabitat occupation would
      increase or decrease with post-fire age. We then tested these predictions using a
      direct (fourth-corner on individual traits and composite traits) and an indirect
      (emergent groups) approach, comparing the benefits of each and also examining the
      degree to which traits were intercorrelated. 3. For the seven individual traits
      that were significant, three followed predictions (body size, abundance of burrow
      ambushers and burrowers was greater in recently burnt sites); two were opposite
      (species with heavy sclerotisation of the cephalothorax and longer time to
      maturity were in greater abundance in long unburnt and recently burnt sites
      respectively); and two displayed response patterns more complex than predicted
      (abdominal scutes displayed a U-shaped response and dispersal ability a hump
      shaped curve). However, within a given trait, there were few significant
      differences among post-fire ages. 4. Several traits were intercorrelated and
      scores based on composite traits used in a fourth-corner analysis found
      significant patterns, but slightly different to those using individual traits.
      Changes in abundance with post-fire age were significant for three of the five
      emergent groups. The fourth-corner analysis yielded more detailed results, but
      overall we consider the two approaches complementary. 5. While we found
      significant differences in traits with post-fire age, our results suggest that a
      trait-based approach may not increase predictive power, at least for the
      assemblages of spiders we studied. That said, there are many refinements to
      faunal traits that could increase predictive power.

PMID- 21198588
TI  - Spatio-temporal variation in territory quality and oxidative status: a natural
      experiment in the Seychelles warbler (Acrocephalus sechellensis).
AB  - 1. Fluctuations in the quality of the habitat in which an animal lives can have
      major consequences for its behaviour and physiological state. In poor-quality
      habitat with low food availability, metabolically intensive foraging activity is
      likely to result in increased generation of reactive oxygen species, while
      scarcity of food can lead to a weakening of exogenously derived antioxidant
      defences. The consequent oxidant/antioxidant imbalance may lead to elevated
      oxidative stress. 2. Although the link between food availability and oxidative
      stress has been studied in the laboratory, very little is known about this
      relationship in the wild. Here, we investigate the association between territory
      quality (measured through food availability) and oxidative stress in the
      Seychelles warbler (Acrocephalus sechellensis). 3. Seychelles warblers are
      insectivorous birds that inhabit a fixed feeding territory year round.
      Individuals experience profound and rapid local fluctuations in territory quality
      within these territories, owing to changing patterns of vegetation defoliation
      resulting from seasonal changes in prevailing wind direction and wind-borne salt
      spray. 4. As expected, oxidant generation (measured as reactive oxygen
      metabolites; ROMs) was higher when territory quality was low, but there was no
      correlation between territory quality and antioxidant capacity (OXY). The
      negative correlation between territory quality and ROMs was significant between
      individuals and approached significance within individuals, indicating that the
      pattern resulted from individual responses to environmental variation. 5. ROMs
      and OXY levels within individuals were positively correlated, but the
      relationship between territory quality and ROMs persisted after including OXY as
      a covariate, implying that oxidative stress occurs in low territory quality
      conditions. 6. Our results indicate that the oxidative stress balance of an
      individual is sensitive to relatively short-term changes in territory quality,
      which may have consequences for the birds' fitness.

PMID- 21198592
TI  - Single cells for forensic DNA analysis--from evidence material to test tube.
AB  - The purpose of this project was to develop a method that, while providing
      morphological quality control, allows single cells to be obtained from the
      surfaces of various evidence materials and be made available for DNA analysis in
      cases where only small amounts of cell material are present or where only mixed
      traces are found. With the SteREO Lumar.V12 stereomicroscope and UV unit from
      Zeiss, it was possible to detect and assess single epithelial cells on the
      surfaces of various objects (e.g., glass, plastic, metal). A digitally operated
      micromanipulator developed by aura optik was used to lift a single cell from the
      surface of evidence material and to transfer it to a conventional PCR tube or to
      an AmpliGrid((r)) from Advalytix. The actual lifting of the cells was performed
      with microglobes that acted as carriers. The microglobes were held with
      microtweezers and were transferred to the DNA analysis receptacles along with the
      adhering cells. In a next step, the PCR can be carried out in this receptacle
      without removing the microglobe. Our method allows a single cell to be isolated
      directly from evidence material and be made available for forensic DNA analysis.

PMID- 21198593
TI  - The effect of cleaning agents on the ability to obtain DNA profiles using the
      IdentifilerTM and PowerPlex(r) Y multiplex kits.
AB  - A year after the introduction of IdentifilerTM into the forensic DNA laboratories
      of the Institute of Environmental Science and Research Limited (ESR), increasing
      occurrences of dropout of the three loci, D7S820, D18S51, and FGA, were observed
      in samples where the DNA was not degraded and sufficient DNA was present that
      full DNA profiles were to be expected. The dropout was either partial or complete
      at these loci. Full profiles could sometimes be obtained by reamplification of
      samples using the same input amount of DNA. After a thorough investigation of the
      methods and procedures used in the laboratory, the cause of this inhibition was
      identified as the cleaning agent TriGeneTM ADVANCE. This was determined after the
      deliberate addition of varying amounts of different cleaning reagents into the
      DNA amplification reactions. At concentrations of 0.004% TriGeneTM ADVANCE caused
      inhibition resulting in tri-loci dropout. At concentrations of 0.04% and higher,
      complete inhibition was observed. An effect was also seen on the amplification of
      samples using the Y STR profiling system PowerPlex((r)) Y. This work highlights
      the importance of checking all reagents and chemicals prior to use, even those
      with no apparent direct influence on the DNA profiling process.

PMID- 21198594
TI  - Multivariate analysis for estimating the age of a bloodstain.
AB  - Our objective is to provide crime laboratories with a technique for estimating
      the age of a bloodstain. Toward that goal, we have used multiplexed, real-time RT
      PCR (or qPCR) to determine the relative stability of different-sized segments of
      the same RNA species as well as differences in stability between two different
      RNAs' change over time in bloodstains. Our results indicate that a multivariate
      analysis of the changing ratio of the different RNA segments can be used to
      differentiate between samples of different ages in the defined population.
      Bloodstains from 29 of 30 donors could be partitioned into different ages using
      this technique. Although further improvements will be required before this
      approach can be implemented in crime laboratories, the multivariate analysis
      holds promise of providing a reliable approach for temporally linking a
      bloodstain to the commission of a crime or excluding a bloodstain as being
      irrelevant to the case in question.

PMID- 21198595
TI  - Surface-enhanced Raman spectroscopy for trace identification of controlled
      substances: Morphine, codeine, and hydrocodone.
AB  - We obtain the normal Raman and surface-enhanced Raman spectrum of three
      controlled substances: morphine, codeine, and hydrocodone. The spectra are
      assigned with the aid of density functional theory. Because of rather intense
      fluorescence, normal Raman spectra suffer from poor signal-to-noise, even when
      differential subtraction techniques are employed. On the other hand, surface
      enhancement by Ag nanoparticles both enhances the Raman signal and suppresses the
      fluorescence, enabling far more sensitive detection and identification. We also
      present a set of discriminant bands, useful for distinguishing the three
      compounds, despite the similarities in their structures.

PMID- 21198591
TI  - Genetic risk by experience interaction for childhood internalizing problems:
      converging evidence across multiple methods.
AB  - BACKGROUND: Identifying how genetic risk interacts with experience to predict
      psychopathology is an important step toward understanding the etiology of mental
      health problems. Few studies have examined genetic risk by experience interaction
      (G*E) in the development of childhood psychopathology. METHODS: We used both co
      twin and parent mental health as markers of genetic risk to test whether G*E
      predicted internalizing problems in a sample of 8-year-old twins. Multi
      instrument composites were used to characterize both parent and child
      psychopathology, and five experiential risk factors (socioeconomic status, single
      parent upbringing, negative parent-child interactions, number of negative life
      events, negative impact of negative life events) composed a cumulative risk
      index. RESULTS: We found consistent evidence for G*E for child internalizing
      problems, with significant interaction effects emerging both when genetic risk
      was indexed by co-twin mental health and when it was based on parent mental
      health. When co-twin mental health was used to estimate genetic risk, child
      internalizing problems were more heritable for children at low rather than high
      experiential risk. When parent mental health was used to estimate genetic risk,
      the association between genetic risk and internalizing problems was stronger for
      children at elevated experiential risk. Consideration of the interaction effect
      sizes helps to reconcile these findings. CONCLUSIONS: Our results suggest that
      the processes involved in both diathesis-stress and bioecological models of
      development may operate for child internalizing problems. Effect sizes indicated
      that the main effects of genetic and experiential risk were much better
      predictors of child internalizing problems than was their interaction.

PMID- 21198596
TI  - A statistical approach based on accumulated degree-days to predict decomposition
      related processes in forensic studies.
AB  - Using pig carcasses exposed over 3 years in rural fields during spring, summer,
      and fall, we studied the relationship between decomposition stages and degree-day
      accumulation (i) to verify the predictability of the decomposition stages used in
      forensic entomology to document carcass decomposition and (ii) to build a degree
      day accumulation model applicable to various decomposition-related processes.
      Results indicate that the decomposition stages can be predicted with accuracy
      from temperature records and that a reliable degree-day index can be developed to
      study decomposition-related processes. The development of degree-day indices
      opens new doors for researchers and allows for the application of inferential
      tools unaffected by climatic variability, as well as for the inclusion of
      statistics in a science that is primarily descriptive and in need of validation
      methods in courtroom proceedings.

PMID- 21198597
TI  - Letter to the editor--A revisitation of the most common methods of autoerotic
      activity leading to death based on the new standardized classification of
      asphyxia.

PMID- 21198599
TI  - Commentary on: Sauvageau A, Boghossian E. Classification of asphyxia: the need
      for standardization. J Forensic Sci 2010;55(5):1259-67.

PMID- 21198601
TI  - Commentary on: Hlastala MP. Paradigm shift for the alcohol breath test. J
      Forensic Sci 2010;55(2):451-6.

PMID- 21198603
TI  - Commentary on: Iino M, O'Donnell C. Postmortem computed tomography findings of
      upper airway obstruction by food. J Forensic Sci 2010;55(5):1251-8.

PMID- 21198605
TI  - Commentary on: Thonglon T, Chaikum N. Magnetic fingerprint powder from a mineral
      indigenous to Thailand. J Forensic Sci 2010;55(5):1343-6.

PMID- 21198607
TI  - Sex estimation from foot dimensions in an indigenous Indian population.
AB  - Dismembered/severed human remains are frequently found in cases of mass disasters
      and criminal mutilation. Sex estimation from foot dimensions, therefore, has a
      vital role in establishing personal identity. There is a paucity of literature on
      this issue from various Indian populations. The "Rajbanshi" is one such
      indigenous population located in the state of West Bengal, India. The present
      study attempts to estimate sex from foot length, foot breadth, and foot index
      among 350 living adult Rajbanshi (175 men and 175 women) individuals (age range:
      18-50 years). The study concludes that foot dimensions show significant sex
      differences. Both sectioning point and regression analyses can be used to
      estimate sex from foot dimensions. However, multiple regression models appear to
      have the maximum accuracy in sex differentiation. Although statistically
      significant sex differences are evident for foot index, its practical utility
      appears to be limited because of considerable overlap.

PMID- 21198608
TI  - A simple technique for imaging the human skeleton using a flatbed scanner.
AB  - A simple technique for imaging the human skeleton with a flatbed scanner is
      presented using the auricular surface of the ilium as an example. A flatbed
      scanner with resolution capabilities of 600 dpi or greater allows for images of
      human bones. The auricular surface of the ilium was selected to demonstrate this
      technique as it is a fairly three-dimensional area that can be difficult to
      record photographically. Fifty left ilia of various ages at death from the Athens
      Collection were selected from which three observers (SCF, CE, and IM) scored the
      morphology of the auricular surface using a well-established aging method.
      Observations were taken of the dry bone, of digital photographs of the bone, and
      of scanned images of the bone, and in that sequence. Results indicate that scores
      of scanned images are equivalent or better than digital images of the same ilia.
      This technique allows for sharing data electronically with ease.

PMID- 21198609
TI  - A simple identification method of saliva by detecting Streptococcus salivarius
      using loop-mediated isothermal amplification.
AB  - We previously reported that detection of Streptococcus salivarius is feasible for
      proving the presence of saliva in a forensic sample. Here, a simple and rapid
      method for the detection of S. salivarius in forensic samples was developed that
      uses loop-mediated isothermal amplification (LAMP). The LAMP primer set was
      designed using S. salivarius-specific sequences of glucosyltransferase K. To
      simplify the procedure, the sample was prepared by boiling and mutanolysin
      treatment only, and the entire analytical process was completed within 2.5 h. The
      cut-off value was set at 0.1 absorbance units, measured at 660 nm, upon
      termination of the reaction. S. salivarius was identified in all saliva samples,
      but was not detected in other body fluids or on the skin surface. Using this
      method, S. salivarius was successfully detected in various mock forensic samples.
      We therefore suggest that this approach is useful for the identification of
      saliva in forensic practice.

PMID- 21198610
TI  - Moistened hands do not necessarily allude to high quality fingerprints: the
      relationship between palmar moisture and fingerprint donorship.
AB  - We explored the quality distribution of ninhydrin-developed prints on A4 bond
      paper in two groups of individuals, in Israel and in India. While the quality
      distributions of the developed marks in both countries had some dissimilarities,
      both groups showed the expected bell-shape distribution, with the majority of the
      donors belonging to the central zone, defined as "average" or "good." Attempt was
      made to correlate between a physiological feature, palmar moisture, and the
      fingerprint donorship. As a rule, high fingermark quality could be associated
      with sweating hands, but there were individuals with moist palms whose
      fingermarks had a low score and vice versa. This finding supports the logical but
      hitherto unproven assumption that besides the amount of palmar sweat, the other
      physiological factor governing the prints' quality is the total amount of
      substrate, amino acids in this case, in the latent deposits, which depends on the
      substrate concentration in the sweat.

PMID- 21198612
TI  - Full STR profile of a 67-year-old bone found in a fresh water lake.
AB  - DNA extraction from and DNA typing of fresh water-exposed aged bone specimens
      poses a challenging task and is not very well examined. This study presents a new
      method to extract typable DNA from such problematic bone specimens. The procedure
      comprises low-heat drilling and cryogrinding, mild lysis conditions, and silica
      column-based DNA cleaning. DNA quantity is assessed by quantitative PCR prior to
      short tandem repeat (STR) amplification. The procedure was employed with a 67
      year-old tibia bone fragment recovered from a fresh water lake and succeeded to
      produce a full STR profile using the MPX-SP1 and MPX-SP2 mini-STR kits and a
      partial profile with 12 successfully amplified STRs using the Identifiler STR
      kit. The new method for the extraction of DNA from aged fresh water-exposed bone
      specimens presented herein was successfully applied to prepare DNA of sufficient
      quality and quantity to generate a full STR profile.

PMID- 21198611
TI  - Confidence interval of the likelihood ratio associated with mixed stain DNA
      evidence.
AB  - Likelihood ratios are necessary to properly interpret mixed stain DNA evidence.
      They can flexibly consider alternate hypotheses and can account for population
      substructure. The likelihood ratio should be seen as an estimate and not a fixed
      value, because the calculations are functions of allelic frequency estimates that
      were estimated from a small portion of the population. Current methods do not
      account for uncertainty in the likelihood ratio estimates and are therefore an
      incomplete picture of the strength of the evidence. We propose the use of a
      confidence interval to report the consequent variation of likelihood ratios. The
      confidence interval is calculated using the standard forensic likelihood ratio
      formulae and a variance estimate derived using the Taylor expansion. The formula
      is explained, and a computer program has been made available. Numeric work shows
      that the evidential strength of DNA profiles decreases as the variation among
      populations increases.

PMID- 21198613
TI  - Mismatched multiplex PCR amplification and subsequent RFLP analysis to
      simultaneously identify polymorphisms of erythrocytic ESD, GLO1, and GPT genes.
AB  - ESD (esterase D), GLO1 (glyoxalase I), and GPT (glutamate pyruvate transaminase)
      are human erythrocytic isoenzymes and have previously been applied in forensic
      medicine caseworks. The molecular bases of the polymorphic gene expression
      products have been demonstrated to be because of SNPs in respective coding
      regions. However, it has not been revealed whether the SNPs conferring the
      polymorphisms to the aforementioned erythrocytic isoenzymes could be
      simultaneously detected by using a simple PCR method. In this study, we used
      mismatched primers to simultaneously amplify three common isoenzyme loci so that
      all amplified products contained the same Hph I cleavage sites. The products were
      then digested with Hph I and electrophoretically separated and stained so that
      alleles were identified. The accumulated values for the probability of
      discrimination power and excluding the probability of paternity to the
      aforementioned systems attained 90.41% and 41.72%, respectively, in the Chinese
      Han population. This assay could be extremely valuable for future forensic
      medicine practices.

PMID- 21198614
TI  - Rapid direct PCR for ABO blood typing.
AB  - Many different molecular typing methods have been reported to complement routine
      serological ABO blood typing in forensics. However, these ABO genotyping methods
      are often time-consuming and call for an initial DNA isolation step that requires
      the use of expensive kits or reagents. We report here a rapid direct ABO
      genotyping method that eliminates the need for DNA extraction from fresh blood,
      hair, and body fluid stains before PCR. Using a fast PCR instrument and an
      optimized polymerase, the genotyping method-which employs a multiplex allele
      specific primer set for the simultaneous detection of three single-nucleotide
      polymorphism (SNP) sites (nucleotides 261, 526, and 803)-identifies A, B,
      O01/O02, O03, and cis-AB01 alleles in around 70 min from sample collection to
      electropherogram. Not only will this ABO genotyping method be efficiently used in
      forensic practice for rapid screening of samples before full-blown multilocus
      short tandem repeat profiling, but it will also demonstrate an example of rapid
      direct genotyping of SNPs that offers the advantages of time- and cost
      efficiency, convenience, and reduced contamination during DNA analysis.

PMID- 21198615
TI  - A novel method for ABO genotyping using a DNA chip.
AB  - ABO genotyping is often performed to identify the blood type of decomposed
      samples, which is difficult to be determined by a serological test. In this
      study, we developed a simple method for ABO genotyping using a DNA chip. In this
      method, polymerase chain reaction-amplified and fluorescent-labeled fragments in
      the ABO gene and primate-specific D17Z1 were hybridized with DNA probes on a chip
      designed to detect single nucleotide polymorphisms (SNPs) in the ABO gene and
      part of the D17Z1 sequence. Using blood samples from 42 volunteers and 10 animal
      species, we investigated whether the chip could be used to detect SNPs in the ABO
      gene and the D17Z1 sequence. This method was then applied to various forensic
      samples, and it was confirmed that this method was suitable for the simultaneous
      analyses of ABO genotyping and species identification. This method fulfills the
      recent need for the development of rapid and convenient methods for criminal
      investigations.

PMID- 21198616
TI  - Isotope evidence to link a suspect with a pipe bomb multimurder in Austria 1995.
AB  - A bomb attempt in Oberwart, Austria, on February 4, 1995, was the culmination of
      several pipe and letter bomb attempts mainly in Austria. The pipe bomb had been
      mounted on a self-made gypsum (plaster of Paris) pedestal and exploded when
      touched, killing four persons. With a level of 200 tritium units (TU), the water
      extracted from the gypsum pedestal was unusually enriched in tritium (3H)
      compared to an environmental level of about 20 TU at that time. Investigation of
      the 3H content of air moisture in the living room of an arrested suspect showed
      values of about 1000 TU (normally, 50 TU is not exceeded). Additionally, water
      used as sealing liquid in a glass with nitroglycerine found in the living room
      was also significantly enriched in 3H (>400 TU). The living room therefore
      offered the high 3H level environment necessary to lead to elevated 3H
      concentrations in the gypsum pedestal.

PMID- 21198617
TI  - Prediction and preliminary standardization of fire debris constituents with the
      advanced distillation curve method.
AB  - The recent National Academy of Sciences report on forensic sciences states that
      the study of fire patterns and debris in arson fires is in need of additional
      work and eventual standardization. We discuss a recently introduced method that
      can provide predicted evaporation patterns for ignitable liquids as a function of
      temperature. The method is a complex fluid analysis protocol, the advanced
      distillation curve approach, featuring a composition explicit data channel for
      each distillate fraction (for qualitative, quantitative, and trace analysis), low
      uncertainty temperature measurements that are thermodynamic state points that can
      be modeled with an equation of state, consistency with a century of historical
      data, and an assessment of the energy content of each distillate fraction. We
      discuss the application of the method to kerosenes and gasolines and outline how
      expansion of the scope of fluids to other ignitable liquids can benefit the
      criminalist in the analysis of fire debris for arson.

PMID- 21198618
TI  - Simultaneous identification and delta13C classification of drugs using GC with
      concurrent single quadrupole and isotope ratio mass spectrometers.
AB  - In this study, delta13C values of six cocaine samples were identified and
      classified using a single quadrupole mass spectrometer and an isotope ratio mass
      spectrometry (IRMS) as simultaneous gas chromatography detectors. Our instrument
      modification is simple to use and is useful (i) when the sample is of limited
      size or can only be injected once, (ii) to help identify peaks in a complicated
      IRMS chromatogram, and (iii) to help differentiate very simple systems when
      impurity profiling is not possible. The EI-MS confirmed the identity of cocaine
      in each sample. The IRMS data distinguished 12 of the 15 possible pair-wise
      comparisons at the 95% CL. Three samples could not be differentiated by their
      delta13C ratios for cocaine. ANOVA demonstrated that the measurement variance was
      consistently larger than the sample variance. As the delta13C values clearly
      show, this technique enables the exclusion of a potential common source even when
      two samples have otherwise identical chemical and physical properties.

PMID- 21198619
TI  - A new method for casting three-dimensional shoeprints and tire marks with dental
      stone.
AB  - Dental stone is used as the major material for recovering three-dimensional
      shoeprints and tire tracks from crime scenes. The procedure for using dental
      stone sparsely changed over the years. There are two common methods for mixing
      dental stone: (i) a premeasured amount of dental stone is put in a zip-lock bag
      to which water is added, and (ii) the water and dental stone are mixed in a
      bucket. We suggest a novel rapid and efficient method of mixing dental stone and
      water in a bottle. These methods were compared at equal conditions. The
      parameters measured were the number of air bubbles, the strength of the cast, the
      ease of use, and the sharpness and quality of the accidental characteristics
      present in the cast. The proposed bottle method has the advantages of both the
      bucket and the zip-lock methods hence it combines strength, sharpness, high
      quality, and ease of use.

PMID- 21198620
TI  - Bite marks: physical properties of ring adhesion to skin-phase 1.
AB  - Unsupported excised skin may shrink by as much as 50% or more. In 1981, a method
      was developed for ring adhesion to skin with the goal of minimizing tissue
      distortion upon excision. Five modified versions of the technique bearing the
      author's name followed (Dorion types I, II, III, IV, and V). The scientific
      literature reveals little supporting empirical evidence for the preferential use
      of one adhesive/suturing technique over another. This study compares the use of
      various bonding materials (Loctite Super Glue gel((r)) , DermabondTM, VetbondTM),
      cleaning agents (ethanol, dishwashing liquid, and shaving cream), and depilatory
      (Veet((r)) ) on the effects of ring adhesion to skin. The conclusions indicate
      that surface wetness is the most influential factor affecting ring adhesion to
      skin, followed by the type of bonding material, its "freshness," and by the
      cleaning agent used to prepare the skin. The use of a depilatory or shaving cream
      is to be avoided.

PMID- 21198621
TI  - Dental age assessment: the applicability of Demirjian method in eastern Turkish
      children.
AB  - In the literature, little is known about the applicability of this method in
      Turkish children. The aim of this study was, therefore, to evaluate the
      reliability of Demirjian method of age estimation when used for eastern Turkish
      children. A retrospective study was performed on a sample of panoramic
      radiographs taken from 807 healthy eastern Turkish children. The stages of dental
      maturity of the mandibular left seven permanent teeth for each subject using the
      eight radiographic dental maturity stages demonstrated by Demirjian were
      evaluated. A paired t-test was used for statistical analysis. The mean difference
      between the chronological and dental ages ranged from 0.2 to 1.9 years in girls
      and from 0.4 to 1.3 years in boys. The differences between the chronological and
      dental ages were statistically significant in all age groups. The applicability
      of Demirjian method is not suitable for eastern Turkish population.

PMID- 21198622
TI  - Effects of histological staining on the analysis of human DNA from archived
      slides.
AB  - Archived slides of cell smears treated with histological stains for sperm
      detection are often the only source of DNA available when cold cases are
      reopened. There have been conflicting reports as to the negative effects of
      particular histological stains on DNA recovery and quality from human cells,
      making stain selection an important consideration for forensic laboratories. This
      study investigates the effect of several staining systems on DNA recovery from
      histological slide samples stored from 0 to 10 weeks. DNA profiles obtained after
      analysis of these samples with AmpFlSTR((r)) IdentifilerTM and increased cycle
      AmpFlSTR((r)) SGM PlusTM short tandem repeat (STR) profiling systems and the
      effects that these stains have on DNA quantity and quality over time are
      described. Results indicate that Christmas Tree and Hematoxylin and Eosin stains
      do not have significantly different effects on DNA quality after 10-week storage
      of slides. This research will assist scientists to select staining systems that
      have minimal deleterious effects on the DNA recovered.

PMID- 21198623
TI  - Increased hematocrit after applications of conducted energy weapons (including
      TASER((r)) devices) to Sus scrofa.
AB  - Conducted energy weapons (CEWs) are used by law enforcement personnel to
      incapacitate individuals quickly and effectively, without intending to cause
      lethality. CEWs have been deployed for relatively long or repeated exposures in
      some cases. In laboratory animal models, central venous hematocrit has increased
      significantly after CEW exposure. Even limited applications (e.g., three 5-sec
      applications) resulted in statistically significant increases in hematocrit.
      Preexposure hematocrit was significantly higher in nonsurvivors versus survivors
      after more extreme CEW applications. The purpose of this technical note is to
      address specific questions that may be generated when examining these results.
      Comparisons among results of CEW applications, other electrical muscle
      stimulation, and exercise/voluntary muscle contraction are included. The
      anesthetized swine appears to be an acceptable animal model for studying changes
      in hematocrit and associated red blood cell changes. Potential detrimental
      effects of increased hematocrit, and considerations during law enforcement use,
      are discussed.

PMID- 21198625
TI  - Handwriting evidence evaluation based on the shape of characters: application of
      multivariate likelihood ratios.
AB  - A novel Bayesian methodology has been developed to quantitatively assess
      handwriting evidence by means of a likelihood ratio (LR) designed for
      multivariate data. This methodology is presented and its applicability is shown
      through a simulated case of a threatening anonymous text where a suspect is
      apprehended. The shape of handwritten characters a, d, o, and q of the
      threatening text was compared with characters of the true writer, and then with
      two other writers, one with similar and one with dissimilar characters shape
      compared to the true writer. In each of these three situations, 100 draws of
      characters were made and the resulting distributions of LR were established to
      consider the natural handwriting variation. LR values supported the correct
      hypothesis in every case. This original Bayesian methodology provides a coherent
      and rigorous tool for the assessment of handwriting evidence, contributing
      undoubtedly to integrate the field of handwriting examination into science.

PMID- 21198624
TI  - Poisoning deaths in Central China (Hubei): A 10-year retrospective study of
      forensic autopsy cases.
AB  - A retrospective study of autopsy cases was conducted at the Department of
      Forensic Medicine, Tongji Medical College (DFM-TMC), in Hubei, China to describe
      the characteristics of poisoning deaths from 1999 to 2008. A total of 212
      poisoning deaths were investigated by DFM-TMC during the 10-year period. The
      poisoning deaths ranged from 17 cases in 1999 to 27 cases in 2008. Of the 212
      cases, 82 deaths (38.7%) were from pesticides, 36 deaths (17.0%) from carbon
      monoxide, 34 deaths (16.0%) from drugs, 22 deaths (10.4%) from alcohol, 17 deaths
      (8.0%) from other chemicals, 15 deaths (7.1%) from poisonous plants and animals,
      and six deaths (2.8%) from heavy metals. Of the 82 pesticide poisoning deaths, 43
      (52.4%) cases were caused by rodenticides, mainly tetramine (N = 39). The
      majority of poisoning deaths were accidents (63.7%), followed by suicides (25.9%)
      and homicides (3.8%). The manner of death could not be determined in 14 cases
      (6.6%).

PMID- 21198626
TI  - Neck and scleral hemorrhage in drowning.
AB  - The determination of the cause and manner of death for a body recovered from the
      water can be difficult because of a lack of autopsy findings specific for
      drowning. This case report describes a 30-year-old man found submerged at the
      bottom of a hotel pool. An autopsy revealed scleral hemorrhages and fascial
      hemorrhages of multiple muscles of the anterior and posterior neck bilaterally.
      No evidence of traumatic injury was on the surface of the body. An investigation
      by law enforcement found no evidence of foul play. The occurrence of petechial
      and neck hemorrhage in a body recovered from the water is controversial, and a
      review of this literature will be given. We suggest that fascial hemorrhages of
      the muscles of the neck, as well as cephalic hemorrhages, can be explained by
      drowning-related elevated central venous pressure that is communicated to the
      head through the valveless veins of the neck.

PMID- 21198627
TI  - Preliminary radiological assessment of age-related change in the trabecular
      structure of the human os pubis.
AB  - This preliminary study examines correlations between age-at-death and changes in
      the trabecular architecture of the human os pubis, utilizing continuous,
      quantitative data from plain film radiography, computed tomography (CT), and
      micro-CT scans of 65 male innominates. Radiography provides nondestructive
      options for assessment, digital preservation, and presentation of human skeletal
      remains; important for forensic and culturally sensitive archaeological
      materials, which must remain unmodified for opposing experts, future researchers,
      or repatriation and reburial. Radiographic techniques permit analysis of remains
      that cannot be disarticulated (e.g., religious proscription, mummies), and
      trabecular measures provide data where traditional surface indicators are
      obscured or damaged. Potentially, robust predictive models derived herein achieve
      R-values of 0.522, 0.447, and 0.731, respectively. Further testing of these
      methods may validate these techniques as further lines of evidence in age
      estimation, with the potential to improve on the accuracy of traditional
      qualitative techniques by providing quantitative, continuous variables in
      predicting skeletal age-at-death.

PMID- 21198628
TI  - Gadolinium-induced oxidative stress triggers endoplasmic reticulum stress in rat
      cortical neurons.
AB  - Introduction of Gadolinium (Gd) to the nervous system is linked to the
      development of neurotoxicity involving both oxidative and endoplasmic reticulum
      (ER) stress. Gd levels (0.2-20 MUm) in the form of gadolinium trichloride
      (GdCl(3)) cause neurotoxicity in vitro. We investigated the signaling pathways in
      primary cultured rat cortical neurons and tested whether GdCl(3) induced
      oxidative and ER stress. Results showed that Gd-induced neural cell death
      followed a rapid accumulation of intracellular reactive oxygen species. In
      addition, Gd exposure resulted in spliced X-box binding protein 1 mRNA and
      increased expression of binding immunoglobulin protein, thus activating
      transcription factor 4 (ATF4), ATF6, and C/EBP homologous protein mRNA. Up
      regulated expression of binding immunoglobulin protein is a hallmark of ER stress
      and C/EBP homologous protein is an ER stress-related pro-apoptotic transcription
      factor. Activation of ER stress downstream substrates, inositol-requiring kinase
      1 and ATF6, was also observed in Gd-treated cells. The neurotoxic effects of Gd
      were blocked by the antioxidant N-acetylcysteine. Results demonstrated that Gd
      induced cytotoxicity in neurons occurs via oxidative injury and ER stress-related
      signal transduction, thus offering new insight into the neurotoxicology of
      gadolinium.

PMID- 21198630
TI  - Long-term effects of neonatal glutamine-enriched nutrition in very-low-birth
      weight infants.
AB  - Several studies in very-low-birth-weight (VLBW) infants have investigated the
      effect of parenteral or enteral glutamine supplementation on morbidity,
      mortality, and outcome in the neonatal period. No evidence of toxicity of
      glutamine supplementation was found in these clinical trials, but the results for
      efficacy on a limited number of outcomes have been mixed. The use of glutamine
      supplementation in VLBW infants has not become routine. Some authors suggest that
      further study in this area is no longer warranted. In this review, more recent
      research in the area of glutamine supplementation is described, which suggests
      additional studies are warranted.

PMID- 21198631
TI  - Dietary fiber type reflects physiological functionality: comparison of grain
      fiber, inulin, and polydextrose.
AB  - Dietary fiber is a nutritional concept based not on physiological functions but
      on defined chemical and physical properties. Recent definitions of dietary fiber
      differentiate inherent plant cell wall-associated fiber from isolated or
      synthetic fiber. For the latter to be defined as fiber, beneficial physiological
      effects should be demonstrated, such as laxative effects, fermentability,
      attenuation of blood cholesterol levels, or postprandial glucose response. Grain
      fibers are a major natural source of dietary fiber worldwide, while inulin, a
      soluble indigestible fructose polymer isolated from chicory, and polydextrose, a
      synthetic indigestible glucose polymer, have more simple structures. Inulin and
      polydextrose show many of the same functionalities of grain fiber in the large
      intestine, in that they are fermentable, bifidogenic, and laxative. The reported
      effects on postprandial blood glucose and fasting cholesterol levels have been
      modest, but grain fibers also show variable effects. New biomarkers are needed to
      link the physiological functions of specific fibers with long-term health
      benefits.

PMID- 21198632
TI  - Relationship between molecular structure of cereal dietary fiber and health
      effects: focus on glucose/insulin response and gut health.
AB  - Epidemiological and animal data show associations between whole grain and dietary
      fiber intakes and disease risk reduction. Dietary fiber can be considered a
      "black box" since its molecular structure can vary significantly. Limited data
      are available linking the health effects of dietary fiber to certain molecular
      structures. The present review was conducted to examine the existing knowledge of
      structure/effect relationships with a focus on human intervention studies that
      examined the relationships between the molecular structure of cereal dietary
      fiber and both the blood glucose and insulin responses and gut health. An
      extensive search of the existing literature was conducted using the PubMed
      database for the period 1993-2008. Of 48 publications originally identified using
      the search criteria, 13 provided molecular information in conjunction with fiber
      type. Several indications show a link between molecular structure and
      physiological effects. Limited data from human intervention trials are available
      to verify hypotheses derived from in vitro studies that relate the molecular
      structure of cereal dietary fiber to both insulin and glucose response and gut
      health.

PMID- 21198633
TI  - Folate metabolism pathway and Plasmodium falciparum malaria infection in
      pregnancy.
AB  - Malaria induced by Plasmodium falciparum is a major cause of mortality. P.
      falciparum has the ability to use host plasma folate as its primary folate
      source. Folate is a cofactor needed for both malaria parasite growth and host
      erythrocyte production. This review examines the possible impairment of the
      folate-mediated one-carbon metabolism pathway as a result of P. falciparum
      malaria infection during pregnancy. Folate deficiency during malaria infection is
      presented, with an emphasis on the controversy regarding the decrease of plasma
      or erythrocyte folate secondary to malaria. Maternal folate deficiency increases
      the risk of adverse pregnancy outcomes. Functional folate deficiency and/or
      increased plasma homocysteine levels during pregnancy of infected women in areas
      endemic for malaria is a probable scenario accentuating the impairment of
      placenta function leading to the occurrence of neural tube defects, low birth
      weights, and intrauterine growth retardations. Potential questions that may be
      answered in future investigations using an appropriate protocol to study pregnant
      women with malaria are also addressed.

PMID- 21198634
TI  - Oral silicon supplementation: an effective therapy for preventing oral aluminum
      absorption and retention in mammals.
AB  - Silicon is an essential element for some lower forms of life. However, it is not
      generally considered an essential nutrient for mammals and the mechanisms
      underlying its potential essentiality remain partially unknown. In recent years,
      a possible association between the aluminum and silicon levels in drinking water
      and Alzheimer's disease (AD) has been suggested. It has been reported that
      silicon might have a protective effect for limiting oral aluminum absorption.
      This review is focused primarily on the potential role of silicon in preventing
      oral aluminum absorption and retention in mammals. The results of a number of
      studies suggest that dietary silicon supplementation could be of therapeutic
      value for preventing chronic aluminum accumulation in the brain, and hence, be a
      potential therapy for AD. However, it must be noted that controversy remains
      about whether aluminum accumulation in the brain is a cause or a consequence of
      AD. It is suggested that further investigation of this issue is warranted.

PMID- 21198635
TI  - Genetics of eating behavior: established and emerging concepts.
AB  - Understanding why we eat and the motivational factors driving food choices is
      important for addressing the epidemics of obesity, diabetes, and cardiovascular
      disease. Eating behavior is a complex interplay of physiological, psychological,
      social, and genetic factors that influence meal timing, quantity of food intake,
      and food preference. Reviewed here is the current and emerging knowledge of the
      genetic influences on eating behavior and how these relate to obesity; particular
      emphasis is placed on the genetics of taste, meal size, and selection, and the
      emerging use of functional magnetic resonance imaging to study neural reactions
      in response to food stimuli in normal, overweight, and obese individuals.

PMID- 21198637
TI  - p38 mitogen-activated protein kinase and PI3-kinase are involved in up-regulation
      of mu opioid receptor transcription induced by cycloheximide.
AB  - Despite several decades of efforts to develop safer, efficacious, and non
      addictive opioids for pain treatment, morphine remains the most valuable
      painkiller in contemporary medicine. Morphine and endogenous mu opioid peptides
      exert their pharmacological actions mainly through the mu opioid receptor (MOR).
      Analgesic effects of opioids in animals are dependent on the MOR expression
      levels, as demonstrated by studies of MOR-knockout mice (homo/heterozygotes) and
      MOR-less expressing mice. Surprisingly, in the course of our investigation to
      understand the mechanisms involved in the regulation of MOR gene expression,
      cycloheximide (CHX), a known protein synthesis inhibitor, markedly induced
      accumulation of MOR mRNAs in both MOR-negative and -positive cells. This
      induction was blocked by inhibitors of phosphoinositide 3-kinase (PI3-K) and p38
      MAPK, but not by a p42/44 MAPK inhibitor. In vitro, CHX was found to activate the
      MOR promoter and this activation was suppressed by inhibition of PI3-K. The
      transcriptional activator Sox18 was recruited to the MOR promoter in CHX-treated
      cells and this recruitment was also inhibited by the PI3-K and p38 MAPK
      inhibitors, Ly294002 and SB203580, respectively. Consistently, acetylation of
      histone H3 and induction of H3-K4 methylation were detected while reductions of
      histone deacetylase 2 binding and H3-K9 methylation were observed on the
      promoter. Furthermore, the MOR mRNA accumulation was almost completely inhibited
      in the presence of actinomycin-D, indicating that this effect occurs mainly
      through activation of the transcriptional machinery. These observations suggest
      that CHX directly induces MOR gene transcription by recruiting the active
      transcription factor Sox18 to the MOR promoter through PI3- and/or p38 MAPK
      pathways.

PMID- 21198638
TI  - Dramatic increase in readthrough acetylcholinesterase in a cellular model of
      oxidative stress.
AB  - Moderate, transient oxidative stress is achieved in SH-SY5Y cells using tertiary
      butylhydroperoxide as oxidant. Over a recovery period of 24 h, the enzymatic
      activity and protein levels of the acetylcholinesterase (AChE) splice variants
      tailed AChE (AChE-T) and readthrough AChE (AChE-R) are monitored. Their time
      dependent correlation to pro- and anti-apoptotic factors, namely caspase 3 and
      Bcl-2, respectively, as well as lactate dehydrogenase release as a measure of
      cell viability is assessed. A distinctly different expression pattern of AChE-T
      as compared with AChE-R is recorded, in that AChE-T shows only a very slight
      increase over a 6 h time period. In contrast, AChE-R rises continuously during
      the recovery period, reaching peak intracellular levels that are up to six times
      higher than control levels 3-4 h post-stress, and is released from cells in
      substantial amounts. Moreover, anti-apoptotic Bcl-2 increases significantly,
      peaking 2-3 h after this AChE-R peak has occurred. We believe this study presents
      the first work that demonstrates - without relying on techniques of over
      expression - the time-dependent correlation between apoptotic processes and
      related rescue mechanisms involving AChE isoforms in a neuronal cell line.

PMID- 21198640
TI  - Dendritic trafficking of brain-derived neurotrophic factor mRNA: regulation by
      translin-dependent and -independent mechanisms.
AB  - Dendritic trafficking and translation of brain-derived neurotrophic factor (BDNF)
      transcripts play a key role in mediating synaptic plasticity. Recently, we
      demonstrated that siRNA-mediated knockdown of translin, an RNA-binding protein,
      impairs KCl-induced dendritic trafficking of BDNF mRNA in cultured hippocampal
      neurons. We have now assessed whether translin deletion impairs dendritic
      trafficking of BDNF mRNA in hippocampal neurons in vivo. We have found that
      translin and its partner protein, trax, undergo dendritic translocation in
      response to treatment with pilocarpine, a pro-convulsant muscarinic agonist that
      increases dendritic trafficking of BDNF mRNA in hippocampal neurons. In translin
      knockout mice, the basal level of dendritic BDNF mRNA is decreased in CA1
      pyramidal neurons. However, translin deletion does not block pilocarpine's
      ability to increase dendritic trafficking of BDNF mRNA indicating that the
      requirement for translin in this process varies with the stimulus employed to
      drive it. Consistent with this inference, we found that dendritic trafficking of
      BDNF mRNA induced by bath application of recombinant BDNF in cultured hippocampal
      neurons, is not blocked by siRNA-mediated knockdown of translin. Taken together,
      these in vivo and in vitro findings indicate that dendritic trafficking of BDNF
      mRNA can be mediated by both translin-dependent and -independent mechanisms.

PMID- 21198639
TI  - Oxidative stress-induced oligomerization inhibits the activity of the non
      receptor tyrosine phosphatase STEP61.
AB  - The neuron-specific tyrosine phosphatase STriatal Enriched Phosphatase (STEP) is
      emerging as an important mediator of glutamatergic transmission in the brain.
      STEP is also thought to be involved in the etiology of neurodegenerative
      disorders that are linked to oxidative stress such as Alzheimer's disease and
      cerebral ischemia. However, the mechanism by which oxidative stress can modulate
      STEP activity is still unclear. In this study, we have investigated whether
      dimerization may play a role in regulating the activity of STEP. Our findings
      show that STEP(61), the membrane associated isoform, can undergo homodimerization
      under basal conditions in neurons. Dimerization of STEP(61) involves
      intermolecular disulfide bond formation between two cysteine residues (Cys 65 and
      Cys 76 respectively) present in the hydrophobic region at the N-terminus specific
      to STEP(61). Oxidative stress induced by hydrogen peroxide leads to a significant
      increase in the formation of dimers and higher-order oligomers of STEP(61). Using
      two substrates, para-nitrophenylphosphate and extracellular-regulated kinase MAPK
      we further demonstrate that oligomerization leads to a significant reduction in
      its enzymatic activity.

PMID- 21198641
TI  - SynArfGEF is a guanine nucleotide exchange factor for Arf6 and localizes
      preferentially at post-synaptic specializations of inhibitory synapses.
AB  - SynArfGEF, also known as BRAG3 or IQSEC3, is a member of the brefeldin A
      resistant Arf-GEF/IQSEC family and was originally identified by screening for
      mRNA species associated with the post-synaptic density fraction. In this study,
      we demonstrate that synArfGEF activates Arf6, using Arf pull down and transferrin
      incorporation assays. Immunohistochemical analysis reveals that synArfGEF is
      present in somata and dendrites as puncta in close association with inhibitory
      synapses, whereas immunoelectron microscopic analysis reveals that synArfGEF
      localizes preferentially at post-synaptic specializations of symmetric synapses.
      Using yeast two-hybrid and pull down assays, we show that synArfGEF is able to
      bind utrophin/dystrophin and S-SCAM/MAGI-2 scaffolding proteins that localize at
      inhibitory synapses. Double immunostaining reveals that synArfGEF co-localizes
      with dystrophin and S-SCAM in cultured hippocampal neurons and cerebellar cortex,
      respectively. Both beta-dystroglycan and S-SCAM were immunoprecipitated from
      brain lysates using anti-synArfGEF IgG. Taken together, these findings suggest
      that synArfGEF functions as a novel regulator of Arf6 at inhibitory synapses and
      associates with the dystrophin-associated glycoprotein complex and S-SCAM.

PMID- 21198643
TI  - Up-regulation of retinoblastoma protein phosphorylation in gingiva after
      cyclosporine A treatment: an in vivo and in vitro study.
AB  - BACKGROUND AND OBJECTIVE: Cyclosporine A can induce gingival cell proliferation;
      however, the precise molecular regulation of the proliferation is uncertain.
      Therefore, this study was carried out to examine, in vivo and in vitro, the
      expression of genes and proteins associated with gingival cell proliferation
      after treatment with cyclosporine A. MATERIAL AND METHODS: Forty Sprague Dawley
      rats with right maxillary posterior edentulous gingivae were assigned to a
      cyclosporine A group (30 mg/kg daily of cyclosporine A, administered orally) or a
      control group (administered mineral oil only). The animals were killed 4 wk after
      treatment. The edentulous gingivae were dissected out and analyzed for the
      expression of proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin
      dependent kinase 4 (CDK4) and retinoblastoma protein (Rb1) mRNA and/or protein,
      and phosphorylated Rb1 (pRb1), by real-time RT-PCR or immunohistochemistry. In
      human gingival fibroblast (HGF) cultures, the expression of PCNA, CDK4, cyclin D1
      and Rb1 proteins and Rb1 phosphorylation were determined by western blotting
      after cyclosporine A treatment (0-10(4) ng/mL). RESULTS: Proliferating cell
      nuclear antigen and cyclin D1 mRNAs (Pcna and Ccnd1, respectively) were expressed
      more strongly in the gingivae of cyclosporine A-treated animals than in the
      gingivae of the controls. Immunohistochemical analyses showed that a greater
      number of gingival cells stained positive for cyclin D1, CDK4 and pRb1 in the
      cyclosporine A group than in the control group. Increased expression of cyclin
      D1, CDK4 and PCNA proteins was observed in HGFs after cyclosporine A treatment.
      The phosphorylation of Rb1 was enhanced in HGFs after treatment with cyclosporine
      A at concentrations of 10(2)-10(3) ng/mL. CONCLUSION: The increases in cyclin D1,
      PCNA and CDK4, together with the enhanced phosphorylation of Rb1, suggest that
      cyclosporine A promotes cell-cycle progression through the G(1)/S transition in
      the gingiva.

PMID- 21198642
TI  - Effects of neuroinflammation on the regenerative capacity of brain stem cells.
AB  - In the adult brain, neurogenesis under physiological conditions occurs in the
      subventricular zone and in the dentate gyrus. Although the exact molecular
      mechanisms that regulate neural stem cell proliferation and differentiation are
      largely unknown, several factors have been shown to affect neurogenesis.
      Decreased neurogenesis in the hippocampus has been recognized as one of the
      mechanisms of age-related brain dysfunction. Furthermore, in pathological
      conditions of the central nervous system associated with neuroinflammation,
      inflammatory mediators such as cytokines and chemokines can affect the capacity
      of brain stem cells and alter neurogenesis. In this review, we summarize the
      state of the art on the effects of neuroinflammation on adult neurogenesis and
      discuss the use of the lipopolysaccharide-model to study the effects of
      inflammation and reactive-microglia on brain stem cells and neurogenesis.
      Furthermore, we discuss the possible causes underlying reduced neurogenesis with
      normal aging and potential anti-inflammatory, pro-neurogenic interventions aimed
      at improving memory deficits in normal and pathological aging and in
      neurodegenerative diseases.

PMID- 21198645
TI  - Photobleaching of red fluorescence in oral biofilms.
AB  - BACKGROUND AND OBJECTIVE: Many species of oral bacteria can be induced to
      fluoresce due to the presence of endogenous porphyrins, a phenomenon that can be
      utilized to visualize and quantify dental plaque in the laboratory or clinical
      setting. However, an inevitable consequence of fluorescence is photobleaching,
      and the effects of this on longitudinal, quantitative analysis of dental plaque
      have yet to be ascertained. MATERIAL AND METHODS: Filter membrane biofilms were
      grown from salivary inocula or single species (Prevotella nigrescens and
      Prevotella intermedia). The mature biofilms were then examined in a custom-made
      lighting rig comprising 405 nm light-emitting diodes capable of delivering 220
      W/m(2) at the sample, an appropriate filter and a digital camera; a set-up
      analogous to quantitative light-induced fluorescence digital. Longitudinal sets
      of images were captured and processed to assess the degradation in red
      fluorescence over time. RESULTS: Photobleaching was observed in all instances.
      The highest rates of photobleaching were observed immediately after initiation of
      illumination, specifically during the first minute. Relative rates of
      photobleaching during the first minute of exposure were 19.17, 13.72 and 3.43
      arbitrary units/min for P. nigrescens biofilms, microcosm biofilm and P.
      intermedia biofilms, respectively. CONCLUSION: Photobleaching could be
      problematic when making quantitative measurements of porphyrin fluorescence in
      situ. Reducing both light levels and exposure time, in combination with increased
      camera sensitivity, should be the default approach when undertaking analyses by
      quantitative light-induced fluorescence digital.

PMID- 21198644
TI  - Lactone form 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins)
      stimulate the osteoblastic differentiation of mouse periodontal ligament cells
      via the ERK pathway.
AB  - BACKGROUND AND OBJECTIVE: Recent studies reported that the lactone forms of 3
      hydroxy- 3-methylglutaryl-coenzyme A reductase inhibitors, which are also known
      as statins, have a bone stimulatory effect. However, there are few reports on the
      effect of statins on periodontal ligament cells. This study examined the statin
      induced osteoblastic differentiation of mouse periodontal ligament cells as well
      as its mechanism. MATERIAL AND METHODS: Mouse periodontal ligament cells were
      cultured with lovastatin or simvastatin, and their viability was measured. The
      levels of alkaline phosphatase (ALP), osteocalcin, bone sialoprotein and bone
      morphogenetic protein-2 mRNA expression were evaluated by RT-PCR. The
      osteoblastic differentiation was characterized by the ALP activity and Alizarin
      Red-S staining for calcium deposition. The activity of the osteocalcin gene (OG2)
      and synthetic osteoblast-specific elements (6* OSE) promoter with statins was
      also measured using a luciferase assay. For the signal mechanism of statins, the
      ERK1/2 MAPK activity was determined by western blot analysis. RESULTS: A statin
      treatment at concentrations < 1 MUM did not affect the cell viability. Lovastatin
      or simvastatin at 0.1 MUM increased the levels of ALP, osteocalcin, bone
      sialoprotein and bone morphogenetic protein-2 mRNA in mouse periodontal ligament
      cells. In addition, the ALP activity, mineralized nodule formation and OG2 and
      OSE promoter activity were higher in the lovastatin- or simvastatin-treated cells
      than the control cells. Western blot analysis confirmed that the statins
      stimulated the phosphorylation of ERK1/2. CONCLUSION: Lovastatin and simvastatin
      may stimulate the osteoblastic differentiation of periodontal ligament cells via
      the ERK1/2 pathway. This suggests that the statins may be useful for regenerating
      periodontal hard tissue.

PMID- 21198646
TI  - Photoperiod regulates lung-associated immunological parameters and melatonin
      receptor (Mel1a and Mel1b) in lungs of a tropical bird, Perdicula asiatica.
AB  - We accessed the effects of different photoperiodic regimes, i.e. long (LP;
      20L:4D), short (SP; 4L:20D) and natural day photoperiod during reproductively
      inactive and reproductively active phase on immune parameters of lungs and
      general immunity of Perdicula asiatica. SP increased bronchus-associated lymphoid
      tissue (BALT) and non-BALT nodule size, total leukocyte count, lymphocyte count,
      plasma melatonin level, percent stimulation ratio of lymphocytes and decreased
      testicular activity (weight and testosterone level). LP during both the
      reproductive phases decreased the above-mentioned immune parameters suggesting
      that photoperiod might be regulating lung-associated immune system (LAIS) via
      melatonin. We also extended our study to note the expression of melatonin
      receptor types Mel(1a) and Mel(1b) in lung tissue to support our above statement.
      Western blot analysis showed significant increase in expression of Mel(1a) and
      Mel(1b) receptor types under SP conditions and decreased expression under LP
      condition when compared with control group of both reproductive phases. This
      suggests the probable involvement of Mel(1a) and Mel(1b) receptors in mediation
      of photoperiodic signals to LAIS. P. asiatica is a photoperiodic bird hence
      photoperiodically regulated melatonin hormone and its receptors in the lung might
      be responsible for modulation of lung-associated immunity.

PMID- 21198647
TI  - Photoreaction in BLUF receptors: proton-coupled electron transfer in the flavin
      Gln-Tyr system.
AB  - Photoinduced electron transfer from tyrosine to the flavin chromophore is
      involved in activation of BLUF (sensor of blue light using FAD) photoreceptors.
      We studied the electron transfer (ET) coupled with proton-transfer (PT)
      reactions, by means of XMCQDPT2//CASSCF calculations on a molecular cluster
      model. By defining a minimum active space in the CASSCF calculations, we could
      compute the entire photoreaction pathway. We find that the crossing of the
      locally excited and ET states is located along the flavin bond-stretching
      coordinate. The ET state is stabilized by a proton transfer from the electron
      donor to the electron acceptor. We mapped two different PT pathways from tyrosine
      to flavin via the conserved glutamine. These reactions generate a tautomeric form
      of glutamine. Along the PT coordinates, we find geometries where the ET and the
      electronic ground states degenerate. At the state crossing structures, either
      formation of the ground state biradical intermediate or a relaxation back to the
      Franck-Condon minimum takes places. The computed relaxation pathways reveal that
      the hydrogen bonds involving glutamine in the chromophore-binding pocket control
      BLUF photoefficiency.

PMID- 21198648
TI  - Light-generated paramagnetic intermediates in BLUF domains.
AB  - Blue-light sensitive photoreceptory BLUF domains are flavoproteins, which
      regulate various, mostly stress-related processes in bacteria and eukaryotes. The
      photoreactivity of the flavin adenine dinucleotide (FAD) cofactor in three BLUF
      domains from Rhodobacter sphaeroides, Synechocystis sp. PCC 6803 and Escherichia
      coli have been studied at low temperature using time-resolved electron
      paramagnetic resonance. Photoinduced flavin triplet states and radical-pair
      species have been detected on a microsecond time scale. Differences in the
      electronic structures of the FAD cofactors as reflected by altered zero-field
      splitting parameters of the triplet states could be correlated with changes in
      the amino-acid composition of the various BLUF domains' cofactor binding pockets.
      For the generation of the light-induced, spin-correlated radical-pair species in
      the BLUF domain from Synechocystis sp. PCC 6803, a tyrosine residue near the
      flavin's isoalloxazine moiety plays a critical role.

PMID- 21198649
TI  - Seasonal variation of leaf respiration and the alternative pathway in field-grown
      Populus * canadensis.
AB  - The temperature response of plant respiration varies between species and can
      acclimate to changing temperatures. Mitochondrial respiration in plants has two
      terminal oxidases: the cytochrome c oxidase (COX) and the cyanide-resistant
      alternative oxidase (AOX). In Populus * canadensis var. italica, a deciduous tree
      species, we investigated the temperature response of leaf respiration via the
      alternative and cytochrome pathways, as well as seasonal changes in these
      pathways, using the oxygen isotope fractionation technique. The electron
      partitioning through the alternative pathway (tau(a) ) increased from 0 to 30-40%
      with measurement temperatures from 6 to 30 degrees C at all times measured
      throughout the growing season. tau(a) at the growth temperature (the average
      temperature during 3 days prior to sampling) increased from 12 to 29% from spring
      until late summer and decreased thereafter. Total respiration declined throughout
      the growing season by 50%, concomitantly with decreases in both AOX (64%) and COX
      (32%) protein abundances. Our results provide new insight into the natural
      variability of AOX protein abundances and alternative respiration electron
      partitioning over immediate and seasonal timescales.

PMID- 21198650
TI  - The reliability and validity of the Danish Draft Board Cognitive Ability Test:
      Borge Prien's Prove.
AB  - The Danish Draft Board has used the same test for assessing general cognitive
      ability, the Borge Prien's Prove (BPP), for over 50 years during which time all
      men on reaching the age of 18 become liable for conscription. Data from the test
      has, over the decades, been used in numerous and wide-ranging research studies.
      Nonetheless, owing to the special circumstances of its administration, some
      psychometric properties, which are generally assessed for psychological tests,
      have not previously been investigated for the BPP. First, since the test is only
      used at the assessment phase, retesting with the BPP occurs only rarely and under
      exceptional circumstances. Therefore, its Test-Retest reliability has hitherto
      not been documented. Second, questions have often been raised as to whether the
      validity of the BPP is undermined by either a lack of motivation and under
      performing among some of the men taking the test, being, as they are, compelled
      to do so, and/or by gradual obsolescence of the test over the decades of its use.
      We here present findings from three new studies to show that (a) the BPP has a
      satisfactory Test-Retest reliability, r=0.77, (b) BPP test scores are not
      positively associated with expressed attitude to being called upon to serve
      conscription and (c) the correlation between the BPP and a measure of educational
      level has remained stable (at about 0.5) through the last two decades. Taken
      together these three findings further support the continuing value of the BPP in
      research relating to cognitive ability.

PMID- 21198651
TI  - The Better Beginnings, Better Futures project: findings from grade 3 to grade 9.
AB  - Although comprehensive and ecological approaches to early childhood prevention
      are commonly advocated, there are few examples of long-term follow-up of such
      programs. In this monograph, we investigate the medium- and long-term effects of
      an ecological, community-based prevention project for primary school children and
      families living in three economically disadvantaged neighborhoods in Ontario,
      Canada. The Better Beginnings, Better Futures (BBBF) project is one of the most
      ambitious Canadian research projects on the long-term impacts of early childhood
      prevention programming to date. Bronfenbrenner's ecological model of human
      development informed program planning, implementation, and evaluation. Using a
      quasi-experimental design, the BBBF longitudinal research study involved 601
      children and their families who participated in BBBF programs when children were
      between 4 and 8 years old and 358 children and their families from
      sociodemographically matched comparison communities. We collected extensive
      child, parent, family, and community outcome data when children were in Grade 3
      (age 8-9), Grade 6 (age 11-12), and Grade 9 (age 14-15). The BBBF mandate was to
      develop programs that would positively impact all areas of child's development;
      our findings reflect this ecological approach. We found marked positive effects
      in social and school functioning domains in Grades 6 and 9 and evidence of fewer
      emotional and behavioral problems in school across the three grades. Parents from
      BBBF sites reported greater feelings of social support and more positive ratings
      of marital satisfaction and general family functioning, especially at the Grade 9
      follow-up. Positive neighborhood-level effects were also evident. Economic
      analyses at Grade 9 showed BBBF participation was associated with government
      savings of $912 per child. These findings provide evidence that an affordable,
      ecological, community-based prevention program can promote long-term development
      of children living in disadvantaged neighborhoods and produce monetary benefits
      to government as soon as 7 years after program completion.

PMID- 21198660
TI  - Climate change adaptation in New York City: building a risk management response.

PMID- 21198661
TI  - Vaccines.

PMID- 21198662
TI  - Smallpox vaccines: targets of protective immunity.
AB  - The eradication of smallpox, one of the great triumphs of medicine, was
      accomplished through the prophylactic administration of live vaccinia virus, a
      comparatively benign relative of variola virus, the causative agent of smallpox.
      Nevertheless, recent fears that variola virus may be used as a biological weapon
      together with the present susceptibility of unimmunized populations have spurred
      the development of new-generation vaccines that are safer than the original and
      can be produced by modern methods. Predicting the efficacy of such vaccines in
      the absence of human smallpox, however, depends on understanding the correlates
      of protection. This review outlines the biology of poxviruses with particular
      relevance to vaccine development, describes protein targets of humoral and
      cellular immunity, compares animal models of orthopoxvirus disease with human
      smallpox, and considers the status of second- and third-generation smallpox
      vaccines.

PMID- 21198665
TI  - DNA vaccines: an historical perspective and view to the future.
AB  - This review provides a detailed look at the attributes and immunologic mechanisms
      of plasmid DNA vaccines and their utility as laboratory tools as well as
      potential human vaccines. The immunogenicity and efficacy of DNA vaccines in a
      variety of preclinical models is used to illustrate how they differ from
      traditional vaccines in novel ways due to the in situ antigen production and the
      ease with which they are constructed. The ability to make new DNA vaccines
      without needing to handle a virulent pathogen or to adapt the pathogen for
      manufacturing purposes demonstrates the potential value of this vaccine
      technology for use against emerging and epidemic pathogens. Similarly,
      personalized anti-tumor DNA vaccines can also readily be made from a biopsy.
      Because DNA vaccines bias the T-helper (Th) cell response to a Th1 phenotype, DNA
      vaccines are also under development for vaccines against allergy and autoimmune
      diseases. The licensure of four animal health products, including two
      prophylactic vaccines against infectious diseases, one immunotherapy for cancer,
      and one gene therapy delivery of a hormone for a food animal, provides evidence
      of the efficacy of DNA vaccines in multiple species including horses and pigs.
      The size of these target animals provides evidence that the somewhat
      disappointing immunogenicity of DNA vaccines in a number of human clinical trials
      is not due simply to the larger mass of humans compared with most laboratory
      animals. The insights gained from the mechanisms of protection in the animal
      vaccines, the advances in the delivery and expression technologies for increasing
      the potency of DNA vaccines, and encouragingly potent human immune responses in
      certain clinical trials, provide insights for future efforts to develop DNA
      vaccines into a broadly useful vaccine and immunotherapy platform with
      applications for human and animal health.

PMID- 21198663
TI  - Therapeutic cancer vaccines: are we there yet?
AB  - Enthusiasm for therapeutic cancer vaccines has been rejuvenated with the recent
      completion of several large, randomized phase III clinical trials that in some
      cases have reported an improvement in progression free or overall survival.
      However, an honest appraisal of their efficacy reveals modest clinical benefit
      and a frequent requirement for patients with relatively indolent cancers and
      minimal or no measurable disease. Experience with adoptive cell transfer-based
      immunotherapies unequivocally establishes that T cells can mediate durable
      complete responses, even in the setting of advanced metastatic disease. Further,
      these findings reveal that the successful vaccines of the future must confront:
      (i) a corrupted tumor microenvironment containing regulatory T cells and
      aberrantly matured myeloid cells, (ii) a tumor-specific T-cell repertoire that is
      prone to immunologic exhaustion and senescence, and (iii) highly mutable tumor
      targets capable of antigen loss and immune evasion. Future progress may come from
      innovations in the development of selective preparative regimens that eliminate
      or neutralize suppressive cellular populations, more effective immunologic
      adjuvants, and further refinement of agents capable of antagonizing immune check
      point blockade pathways.

PMID- 21198666
TI  - Regulation of immune responses to HPV infection and during HPV-directed
      immunotherapy.
AB  - The recent development of vaccines prophylactic against human papillomavirus
      (HPV) infection has the potential to reduce the incidence of cervical cancer
      globally by up to 70% over the next 40 years, if universal immunization is
      adopted. As these prophylactic vaccines do not alter the natural history of
      established HPV infection, immunotherapies to treat persistent HPV infection and
      associated precancers would be of benefit to assist with cervical cancer control.
      Efforts to develop immuno-therapeutic vaccines have been hampered by the relative
      non-immunogenicity of HPV infection, by immunoregulatory processes in skin, and
      by subversion of immune response induction and immune effector functions by
      papillomavirus proteins. This review describes HPV-specific immune responses
      induced by viral proteins, their regulation by host and viral factors, and
      highlights some conclusions from our own recent research.

PMID- 21198667
TI  - Prospects for prophylactic and therapeutic vaccines against the hepatitis C
      viruses.
AB  - Encouraging efficacy data have been obtained in the hepatitis C virus (HCV)
      chimpanzee model using prophylactic vaccines comprising adjuvanted recombinant
      envelope gpE1/gpE2 glycoproteins or prime/boost immunization regimens using
      defective adenoviruses and plasmid DNA expressing non-structural genes. While
      usually not resulting in sterilizing immunity after experimental challenge, the
      progression to chronic, persistent infection (which is responsible for HCV
      associated pathogenicity in human) is inhibited. These and other vaccine
      candidates are in clinical development for both prophylactic as well as possible
      therapeutic applications. Given that other vaccines tested in the chimpanzee
      model may be possibly increasing the rate of chronicity, it is very important
      that this model continues to be available and used prior to initiation of
      clinical development. Several vaccine monotherapy trials in chronically infected
      HCV patients are resulting in small declines in viral load, suggesting that in
      future, combining vaccination with antiviral drug treatment may be beneficial.

PMID- 21198664
TI  - Immunization delivered by lentiviral vectors for cancer and infectious diseases.
AB  - The increasing level of understanding of the lentivirus biology has been
      instrumental in shaping the design strategy of creating therapeutic lentiviral
      delivery vectors. As a result, lentiviral vectors have become one of the most
      powerful gene transfer vehicles. They are widely used for therapeutic purposes as
      well as in studies of basic biology, due to their unique characteristics.
      Lentiviral vectors have been successfully employed to mediate durable and
      efficient antigen expression and presentation in dendritic cells both in vitro
      and in vivo, leading to the activation of cellular immunity and humoral
      responses. This capability makes the lentiviral vector an ideal choice for
      immunizations that target a wide range of cancers and infectious diseases.
      Further advances into optimizing the vector system and understanding the
      relationship between the immune system and diseases pathogenesis will only
      augment the potential benefits and utility of lentiviral vaccines for human
      health.

PMID- 21198668
TI  - Living in a house of cards: re-evaluating CD8+ T-cell immune correlates against
      HIV.
AB  - The Merck STEP and the Thai RV144 human immunodeficiency virus (HIV) vaccine
      trials confirmed that we still have a long way to go before developing a
      prophylactic HIV vaccine. The main issue at hand is that we have yet to identify
      an immunological correlate of protection against HIV. While many question the T
      cell-based approach towards vaccine development, it is likely that T cells will
      be a necessary part of any vaccine strategy. CD8(+) T cells remain an attractive
      option because of their ability to specifically recognize and eliminate virally
      infected host cells. In this review, we recapitulate the evidence for CD8(+) T
      cells as an immunological correlate against HIV, but more importantly, we assess
      the means by which we evaluate their antiviral capacity. To achieve a
      breakthrough in the domain of T-cell-based HIV vaccine development, it has become
      abundantly clear that we must overhaul our system of immune monitoring and come
      up with a 'rational' tactic to evaluate the efficacy of HIV-specific CD8(+) T
      cells.

PMID- 21198671
TI  - Influenza vaccine immunology.
AB  - Studying the spread of influenza in human populations and protection by influenza
      vaccines provides important insights into immunity against influenza. The 2009
      H1N1 pandemic has taught the most recent lessons. Neutralizing and receptor
      blocking antibodies against hemagglutinin are the primary means of protection
      from the spread of pandemic and seasonal strains. Anti-neuraminidase antibodies
      seem to play a secondary role. More broadly cross-reactive forms of immunity may
      lessen disease severity but are insufficient to prevent epidemic spread. Priming
      by prior exposure to related influenza strains through infection or immunization
      permits rapid, potent antibody responses to immunization. Priming is of greater
      importance to the design of immunization strategies than the immunologically
      fascinating phenomenon of dominant recall responses to previously encountered
      strains (original antigenic sin). Comparisons between non-adjuvanted inactivated
      vaccines and live attenuated vaccines demonstrate that both can protect, with
      some advantage of live attenuated vaccines in children and some advantage of
      inactivated vaccines in those with multiple prior exposures to influenza
      antigens. The addition of oil-in-water emulsion adjuvants to inactivated vaccines
      provides enhanced functional antibody titers, greater breadth of antibody cross
      reactivity, and antigen dose sparing. The MF59 adjuvant broadens the distribution
      of B-cell epitopes recognized on HA and NA following immunization.

PMID- 21198670
TI  - Biological challenges and technological opportunities for respiratory syncytial
      virus vaccine development.
AB  - Respiratory syncytial virus (RSV) is an important cause of respiratory disease
      causing high rates of hospitalizations in infants, significant morbidity in
      children and adults, and excess mortality in the elderly. Major barriers to
      vaccine development include early age of RSV infection, capacity of RSV to evade
      innate immunity, failure of RSV-induced adaptive immunity to prevent reinfection,
      history of RSV vaccine-enhanced disease, and lack of an animal model fully
      permissive to human RSV infection. These biological challenges, safety concerns,
      and practical issues have significantly prolonged the RSV vaccine development
      process. One great advantage compared to other difficult viral vaccine targets is
      that passively administered neutralizing monoclonal antibody is known to protect
      infants from severe RSV disease. Therefore, the immunological goals for vaccine
      development are to induce effective neutralizing antibody to prevent infection
      and to avoid inducing T-cell response patterns associated with enhanced disease.
      Live-attenuated RSV and replication-competent chimeric viruses are in advanced
      clinical trials. Gene-based strategies, which can control the specificity and
      phenotypic properties of RSV-specific T-cell responses utilizing replication
      defective vectors and which may improve on immunity from natural infection, are
      progressing through preclinical testing. Atomic level structural information on
      RSV envelope glycoproteins in complex with neutralizing antibodies is guiding
      design of new vaccine antigens that may be able to elicit RSV-specific antibody
      responses without induction of RSV-specific T-cell responses. These new
      technologies may allow development of vaccines that can protect against RSV
      mediated disease in infants and establish a new immunological paradigm in the
      host to achieve more durable protection against reinfection.

PMID- 21198669
TI  - Immunology of gut mucosal vaccines.
AB  - Understanding the mechanisms underlying the induction of immunity in the
      gastrointestinal mucosa following oral immunization and the cross-talk between
      mucosal and systemic immunity should expedite the development of vaccines to
      diminish the global burden caused by enteric pathogens. Identifying an
      immunological correlate of protection in the course of field trials of efficacy,
      animal models (when available), or human challenge studies is also invaluable. In
      industrialized country populations, live attenuated vaccines (e.g. polio,
      typhoid, and rotavirus) mimic natural infection and generate robust protective
      immune responses. In contrast, a major challenge is to understand and overcome
      the barriers responsible for the diminished immunogenicity and efficacy of the
      same enteric vaccines in underprivileged populations in developing countries.
      Success in developing vaccines against some enteric pathogens has heretofore been
      elusive (e.g. Shigella). Different types of oral vaccines can selectively or
      inclusively elicit mucosal secretory immunoglobulin A and serum immunoglobulin G
      antibodies and a variety of cell-mediated immune responses. Areas of research
      that require acceleration include interaction between the gut innate immune
      system and the stimulation of adaptive immunity, development of safe yet
      effective mucosal adjuvants, better understanding of homing to the mucosa of
      immunologically relevant cells, and elicitation of mucosal immunologic memory.
      This review dissects the immune responses elicited in humans by enteric vaccines.

PMID- 21198672
TI  - Use of defined TLR ligands as adjuvants within human vaccines.
AB  - Our improved understanding of how innate immune responses can be initiated and
      how they can shape adaptive B- and T-cell responses is having a significant
      impact on vaccine development by directing the development of defined adjuvants.
      Experience with first generation vaccines, as well as rapid advances in
      developing defined vaccines containing Toll-like receptor ligands (TLRLs),
      indicate that an expanded number of safe and effective vaccines containing such
      molecules will be available in the future. In this review, we outline current
      knowledge regarding TLRs, detailing the different cell types that express TLRs,
      the various signaling pathways TLRs utilize, and the currently known TLRLs. We
      then discuss the current status of TLRLs within vaccine development programs,
      including the importance of appropriate formulation, and how recent developments
      can be used to better define the mechanisms of action of vaccines. Finally, we
      introduce the possibility of using TLRLs, either in combination or with non
      TLRLs, to synergistically potentiate vaccine-induced responses to provide not
      only prophylactic, but therapeutic protection against infectious diseases and
      cancer.

PMID- 21198673
TI  - Immunogenomics and systems biology of vaccines.
AB  - Vaccines represent a potent tool to prevent or contain infectious diseases with
      high morbidity or mortality. However, despite their widespread use, we still have
      a limited understanding of the mechanisms underlying the effective elicitation of
      protective immune responses by vaccines. Recent research suggests that this
      represents the cooperative action of the innate and adaptive immune systems.
      Immunity is made of a multifaceted set of integrated responses involving a
      dynamic interaction of thousands of molecules, whose list is constantly updated
      to fill the several empty spaces of this puzzle. The recent development of new
      technologies and computational tools permits the comprehensive and quantitative
      analysis of the interactions between all of the components of immunity over time.
      Here, we review the role of the innate immunity in the host response to vaccine
      antigens and the potential of systems biology in providing relevant and novel
      insights in the mechanisms of action of vaccines to improve their design and
      effectiveness.

PMID- 21198675
TI  - Progress and novel strategies in vaccine development and treatment of anthrax.
AB  - The lethal anthrax disease is caused by spores of the gram-positive Bacillus
      anthracis, a member of the cereus group of bacilli. Although the disease is very
      rare in the Western world, development of anthrax countermeasures gains
      increasing attention due to the potential use of B. anthracis spores as a bio
      terror weapon. Protective antigen (PA), the non-toxic subunit of the bacterial
      secreted exotoxin, fulfills the role of recognizing a specific receptor and
      mediating the entry of the toxin into the host target cells. PA elicits a
      protective immune response and represents the basis for all current anthrax
      vaccines. Anti-PA neutralizing antibodies are useful correlates for protection
      and for vaccine efficacy evaluation. Post exposure anti-toxemic and anti
      bacteremic prophylactic treatment of anthrax requires prolonged antibiotic
      administration. Shorter efficient postexposure treatments may require active or
      passive immunization, in addition to antibiotics. Although anthrax is
      acknowledged as a toxinogenic disease, additional factors, other than the
      bacterial toxin, may be involved in the virulence of B. anthracis and may be
      needed for the long-lasting protection conferred by PA immunization. The search
      for such novel factors is the focus of several high throughput genomic and
      proteomic studies that are already leading to identification of novel targets for
      therapeutics, for vaccine candidates, as well as biomarkers for detection and
      diagnosis.

PMID- 21198674
TI  - From optical bench to cageside: intravital microscopy on the long road to
      rational vaccine design.
AB  - No antiviral vaccine is perfect. For some important pathogens, there are no
      effective vaccines. Many current vaccines are based on the working principles of
      Jenner and Pasteur, that is, empiric administration of attenuated or inactivated
      forms of the pathogen. Tapping the full potential of vaccination requires a
      thorough understanding of the mechanism of immune activation by pathogens and
      their individual components. Though the rate of discovery continues to
      accelerate, the complexity of the immune system is daunting, particularly when
      integrated into the overall physiology of the host. Here, we review the
      application of multiphoton microscopy to examine host-pathogen interactions,
      focusing on our recent efforts to understand mouse CD8(+) T-cell responses to
      viruses at the level of cellular interactions in lymph nodes draining the
      infection site. We also discuss our recent efforts to understand the influence of
      the sympathetic nervous system on antiviral immunity, with the ultimate goal of
      appreciating the traditional elements of immunity as just one facet of the total
      organismal response to infection and immunization.

PMID- 21198677
TI  - Effect of fluoxetine on blood concentrations of serotonin, cortisol and
      dehydroepiandrosterone in canine aggression.
AB  - Canine aggression directed towards people is the most frequent reason for
      referral to behaviour practices. The serotonergic system and the hypothalamic
      pituitary-adrenal (HPA) axis are believed to play an important role in
      controlling aggression. The selective serotonin reuptake inhibitor fluoxetine is
      the most commonly used drug in canine aggression. The aim of the present study
      was to assess the effect of a 30-day-long fluoxetine treatment on the peripheral
      serotonergic system and the HPA axis in canine aggression. To this end, the
      concentrations of serum serotonin (5-HT) and plasma cortisol and
      dehydroepiandrosterone (DHEA) were analysed in a group of aggressive (n = 22) and
      nonaggressive dogs (n = 9) during pre- (day 0) and posttreatment (day 30)
      conditions. Treatment caused a significant decrease in 5-HT concentrations (46%
      in the aggressive group and 32% in the control group). There was a trend towards
      a rise of DHEA/cortisol ratio values after treatment both in the aggressive and
      the control group. The determination of blood 5-HT and the DHEA/cortisol ratio
      could have important clinical applications in the future for deciding which
      animals might benefit from a given treatment as well as for monitoring the
      response. Further large-scale studies with this aim should be carried out to
      obtain sound conclusions.

PMID- 21198678
TI  - Novel gastroretentive controlled-release drug delivery system for amoxicillin
      therapy in veterinary medicine.
AB  - Beta-lactam antimicrobials, commonly used in both veterinary and human medicine,
      generally present short biologic half-lives, whereas their activity is enhanced
      as pathogen exposure is prolonged. These properties necessitate multiple-dose
      regimens of standard dosage forms, thereby hampering pet owner adherence,
      frequently resulting in therapeutic failure. This study presents a novel
      controlled-release gastroretentive oral drug delivery system for beta-lactams
      with which single-dose administration provides an effective antimicrobial course,
      optimizing pharmacokinetic (PK)-pharmacodynamic (PD) profiles, minimizing adverse
      effects and emergence of antimicrobial resistance and facilitating adherence. Our
      prototype sustained-delivery swelling-tablet (SDST), based on a degradable
      hydrophilic polymeric matrix, was designed to enable continuous input of these
      drugs to their absorption sites over several days. Several SDST formulations of
      the beta-lactam amoxicillin were evaluated in in vitro dissolution studies. Two
      formulations were selected for further in vivo canine studies, for determination
      of gastric retention and PK-PD profiling. Prolonged gastric retention times
      maintaining allowed for maintained effective drug concentrations against many
      clinically relevant pathogens for more than 48 h for one formulation and more
      than 5 days for the other. Both SDST formulations offer significant advantages
      over standard immediate-release therapy in achieving PK-PD goals and enhancing
      adherence. The prototypical formulations represent a novel platform which may be
      modified to meet various clinical requirements.

PMID- 21198679
TI  - A novel subcutaneous controlled-release amoxicillin degradable implant for
      extended-interval administration in veterinary medicine.
AB  - Dosage forms of antimicrobials play a critical role in facilitating the
      attainment of pharmacokinetic-pharmacodynamic (PK-PD) targets as well as
      adherence in both veterinary and human medicine. The purpose of this study was to
      develop and evaluate a controlled-release subcutaneous amoxicillin implant for
      single-dose therapy of large ruminants such as goats, sheep, and deer. The
      degradable implant, designed to attain PK-PD targets following single
      administration, was evaluated for amoxicillin release rate and time-concentration
      profile. In vitro release studies demonstrated constant-rate release of
      approximately 40% of amoxicillin content within 96 h. In an in vivo study in
      goats, serving as a model for target animals, a serum concentration of
      approximately 0.4 mg/L was achieved within 8 h of implant insertion and
      maintained for >6 days. In comparison, in control goats given a standard single
      intramuscular amoxicillin dose of 15 mg/kg, amoxicillin peaked at 1.2 mg/L after
      1 h, rapidly dropping to below detection level at 8 h. These results suggest that
      the proposed implant offers a unique modality for animal caregivers to
      conveniently administer a full antimicrobial course following a single dose of an
      efficient PK-PD-optimized dosage form. Furthermore, modifications of implant
      composition may allow for tailoring of its characteristics to various PK, PD,
      microbiological, and clinical requirements.

PMID- 21198680
TI  - Plasma pharmacokinetics of abamectin in fallow deer (Cervus dama dama) following
      subcutaneous administration.
AB  - The pharmacokinetics of abamectin (ABM) following a single subcutaneous
      administration of 200 MUg/kg was evaluated in adult fallow deer by following ABM
      concentration in blood plasma. A nonlinear mixed effects modelling procedure was
      used for pharmacokinetic analysis. The time course of ABM concentration was
      described by a two-compartment model with first-order absorption. Abamectin
      absorption in fallow deer was rapid with a peak plasma concentration of 120.7 +/-
      33.2 ng/mL observed at 19.1 +/- 7.7 h (mean +/- SD). Half-lives of the
      distribution and terminal phase were 17.2 and 119.3 h, respectively. Typical
      apparent clearance of the bioavailable fraction (CL/F) was 0.795 L/h and was
      independent of animal weight. Considering the obtained pharmacokinetic parameters
      in our study, we may assume that effective parasite control in fallow deer is
      obtained using the usual recommended dose of 200 MUg/kg.

PMID- 21198681
TI  - Hypospadias in a Friesian gelding.
AB  - OBJECTIVE: To report clinical signs and management of hypospadias in a horse.
      STUDY DESIGN: Clinical report. ANIMAL: A 6-year-old, Friesian gelding. METHODS:
      Partial phallectomy was performed to resolve contact dermatitis of the pelvic
      limbs and abnormal behavior during urination. Subsequent urethral meatal stenosis
      was treated by revision. RESULTS: Hypospadias and chordee caused altered
      direction of urine flow, contact dermatitis of the pelvic limbs, and abnormal
      behavior. Partial phallectomy and subsequent revision after meatal stenosis
      resolved urine direction, flow and abnormal behavior. CONCLUSIONS: Abnormalities
      of the urinary tract associated with hypospadias can result in urine-induced,
      contact dermatitis and distress during urination, but these complications can be
      resolved by partial phallectomy.

PMID- 21198682
TI  - The influence of fertilizer level and spore density on arbuscular mycorrhizal
      colonization of transgenic Bt 11 maize (Zea mays) in experimental microcosms.
AB  - Crop plants genetically modified for the expression of Bacillus thuringiensis
      (Bt) insecticidal toxins have broad appeal for reducing insect damage in
      agricultural systems, yet questions remain about the impact of Bt plants on
      symbiotic soil organisms. Here, arbuscular mycorrhizal fungal (AMF) colonization
      of transgenic maize isoline Bt 11 (expressing Cry1Ab) and its non-Bt parental
      line (Providence) was evaluated under different fertilizer level and spore
      density scenarios. In a three-way factorial design, Bt 11 and non-Bt maize were
      inoculated with 0, 40, or 80 spores of Glomus mosseae and treated weekly with
      'No' (0 g L(-1) ), 'Low' (0.23 g L(-1) ), or 'High' (1.87 g L(-1) ) levels of a
      complete fertilizer and grown for 60 days in a greenhouse. While no difference in
      AMF colonization was detected between the Bt 11 and Providence maize cultivars in
      the lower spore/higher fertilizer treatments, microcosm experiments demonstrated
      a significant reduction in AMF colonization in Bt 11 maize roots in the 80 spore
      treatments when fertilizer was limited. These results confirm previous work
      indicating an altered relationship between this Bt 11 maize isoline and AMF and
      demonstrate that the magnitude of this response is strongly dependent on both
      nutrient supply and AMF spore inoculation level.

PMID- 21198676
TI  - Vaccines to combat the neglected tropical diseases.
AB  - The neglected tropical diseases (NTDs) represent a group of parasitic and related
      infectious diseases such as amebiasis, Chagas disease, cysticercosis,
      echinococcosis, hookworm, leishmaniasis, and schistosomiasis. Together, these
      conditions are considered the most common infections in low- and middle-income
      countries, where they produce a level of global disability and human suffering
      equivalent to better known conditions such as human immunodeficiency
      virus/acquired immunodeficiency syndrome and malaria. Despite their global public
      health importance, progress on developing vaccines for NTD pathogens has lagged
      because of some key technical hurdles and the fact that these infections occur
      almost exclusively in the world's poorest people living below the World Bank
      poverty line. In the absence of financial incentives for new products, the
      multinational pharmaceutical companies have not embarked on substantive research
      and development programs for the neglected tropical disease vaccines. Here, we
      review the current status of scientific and technical progress in the development
      of new neglected tropical disease vaccines, highlighting the successes that have
      been achieved (cysticercosis and echinococcosis) and identifying the challenges
      and opportunities for development of new vaccines for NTDs. Also highlighted are
      the contributions being made by non-profit product development partnerships that
      are working to overcome some of the economic challenges in vaccine manufacture,
      clinical testing, and global access.

PMID- 21198683
TI  - Regulation of microbial methane production and oxidation by intermittent drainage
      in rice field soil.
AB  - Soil drainage is one of the most promising approaches to mitigate methane (CH(4)
      ) emission from paddy fields. The microbial mechanism for the drainage effect on
      CH(4) emission, however, remains poorly understood. In the present study, we
      determined the effect of short (four drainages of 5-6 days each) and long
      drainage cycles (two drainages of 10-11 days each) on CH(4) emission and analyzed
      the response of the structure and abundance of methanogens and methanotrophs in a
      Chinese rice field soil at the DNA level. Rice biomass production was similar
      between drainage and the practice of continuous flooding. The rate of CH(4)
      emission, however, was reduced by 59% and 85% for the long and short drainage
      cycles, respectively. Quantitative (real-time) PCR analysis revealed that the
      total abundance of archaeal populations decreased by 40% after multiple
      drainages, indicating the inhibitory effects on methanogen growth. The structure
      of the methanogen community as determined by terminal restriction fragment length
      polymorphism analysis, however, remained unaffected by drainages, although it
      varied among rhizosphere, bulk and surface soils. Quantitative PCR analysis of
      the methanotrophic functional pmoA genes revealed that the total abundance of
      methanotrophs in rhizosphere soil increased two to three times after soil
      drainages, indicating a stimulation of methanotroph growth. The CH(4) oxidation
      potential in the rhizosphere soil also increased significantly. Furthermore,
      drainages caused a shift of the methanotrophic community, with a significantly
      increase of type II methanotrophic bacteria in the rhizosphere and surface soil.
      Thus, both inhibition of methanogens and stimulation of methanotrophs were partly
      responsible for the reduction of CH(4) emissions. The methanotroph community,
      however, appeared to react more sensitively to soil drainage compared with the
      methanogen community.

PMID- 21198684
TI  - Compassion fatigue in marriage and family therapy: implications for therapists
      and clients.
AB  - Given that marriage and family therapists are exposed to a wide range of
      circumstances that leave them uniquely vulnerable to experiencing compassion
      fatigue, it is important to examine the stresses and hazards they face and what
      those consequences mean for both themselves and clients. It is essential that
      they identify how compassion fatigue negatively affects the therapeutic
      relationship and overall treatment outcome as well as that of the personal life
      of the family therapist. The marriage and family therapist is responsible and
      ethically obligated to identify and implement ways in which he or she can prevent
      and remedy compassion fatigue.

PMID- 21198685
TI  - Deconstructing heterosexism: becoming an LGB affirmative heterosexual couple and
      family therapist.
AB  - The purpose of this article is to propose a three-step model to help heterosexual
      therapists become more aware of the influence of their own heteronormative
      assumptions, heterosexual privileges, and heterosexual identities on the therapy
      process. This article also provides definitions of concepts central to the
      practice of affirmative therapy with lesbian, gay, and bisexual clients and
      strategies that therapists and clients can use to deconstruct heterosexism in the
      context of therapy.

PMID- 21198686
TI  - Aging issues: unanswered questions in marital and family therapy literature.
AB  - Researchers have reviewed couple and family therapy journals to determine the
      extent to which issues concerning older populations are addressed. In an effort
      to extend previous work, we conducted content analyses of 957 articles published
      in three of the leading marital and family therapy journals between 1997 and
      2006. From the articles, 27 (2.8%) mentioned aging or included older adults in
      their sample. Results indicate that the number of articles emphasizing older
      adults has not substantially increased. While this result has been substantiated
      by other researchers in previous years, a new finding in this study concerns the
      quality of articles on aging issues. The articles reviewed in this study
      indicated a greater focus on aging issues and addressing issues during this life
      cycle stage.

PMID- 21198687
TI  - Contempt and defensiveness in couple relationships related to childhood sexual
      abuse histories for self and partner.
AB  - This study examined the relationship between a history of childhood sexual abuse
      (CSA) for one or both members of a romantic couple and perceptions of contempt
      and defensiveness for self and partner. Data from the Relationship Evaluation
      (RELATE) were analyzed for 10,061 couples. The findings suggest that when either
      or both partner(s) has a history of CSA, contempt and defensiveness in the couple
      relationship are greater than when neither reports a history of CSA. Furthermore,
      the males' experience of CSA had a greater impact on their perceptions of self
      and partner's contempt and defensiveness than females' experience of CSA.
      Explanations of gender differences are offered and implications for future
      research and practice are suggested.

PMID- 21198688
TI  - The unsilencing of military wives: wartime deployment experiences and citizen
      responsibility.
AB  - One of therapists' contemporary moral imperatives is to support American service
      members and their families regardless of personal position on the Global War on
      Terrorism. One way therapists can respond to this imperative is by seeking to
      understand Army wives' experiences during their husbands' wartime deployments.
      Therefore, this study utilized a combination of individual interviews with Army
      wives and a reflecting team of military wives and civilians to explore military
      wives' experiences. Two main themes were identified: the wives' experience was an
      emotional roller coaster and they felt silenced--and could be unsilenced--in
      their interactions with civilians. Therapists working with Army wives should (a)
      normalize the roller-coaster experience; (b) encourage wives to recognize
      negative and positive influencers and explore their idiosyncratic coping skills;
      (c) support positive civilian-military connections; and (d) as a civilian and as
      a therapist, seek to be a positive civilian connection by proactively showing
      support.

PMID- 21198689
TI  - FACES IV and the Circumplex Model: validation study.
AB  - Family Adaptability and Cohesion Evaluation Scale (FACES) IV was developed to tap
      the full continuum of the cohesion and flexibility dimensions from the Circumplex
      Model of Marital and Family Systems. Six scales were developed, with two balanced
      scales and four unbalanced scales designed to tap low and high cohesion
      (disengaged and enmeshed) and flexibility (rigid and chaotic). The six scales in
      FACES IV were found to be reliable and valid. High levels of concurrent,
      construct, and discriminant validity were found and new ratio scores measure the
      balanced and unbalanced level of cohesion and flexibility. A clinical example on
      the use of FACES IV scores to assess family dynamics, plan the treatment, and
      determine the impact of family therapy is provided.

PMID- 21198690
TI  - Utilizing spiritual ecograms with Native American families and children to
      promote cultural competence in family therapy.
AB  - This study signifies an initial step at giving family therapists an important
      assessment tool as they seek to increase cultural competence with Native American
      families and children. To determine the relevancy and consistency of utilizing a
      spiritual ecogram assessment tool with Native Americans, 50 Native American
      participants, with extensive experience with this population, reviewed, rated,
      and gave feedback on its use. Although some limitations were noted, results
      showed that spiritual ecograms were moderately consistent with Native American
      culture and, if used properly, can help family therapists develop culturally
      appropriate interventions with Native American families and children.

PMID- 21198691
TI  - Mental health perceptions and coping strategies of Albanian immigrants and their
      families.
AB  - This study examines the understudied mental health perceptions, treatment, and
      coping strategies of immigrants from the Republic of Albania to Southern
      California regarding themselves and their families. In-depth, semi-structured
      interviews with 12 Albanian immigrants residing in a large Southern California
      population center were conducted. The transcripts of these interviews were
      analyzed. The constant-comparative method was used to analyze the data obtained
      from the interviews. Thirteen themes describing the perceptions and attitudes of
      Albanian immigrants about coping strategies, mental health, and mental health
      issues emerged. Themes are discussed in the context of existing literature, and
      implications for practice, research, and limitations are presented.

PMID- 21198692
TI  - Multicultural supervision: lessons learned about an ongoing struggle.
AB  - This article examines the experiences of seven diverse therapists in a
      supervision course as they wrestled with the real-world application of
      multicultural supervision. Existing literature on multicultural supervision does
      not address the difficulties that arise in addressing multicultural issues in the
      context of the supervision relationship. The experiences of six supervisory
      candidates and one mentoring supervisor in addressing multicultural issues in
      supervision are explored. Guidelines for conversations regarding multicultural
      issues are provided.

PMID- 21198693
TI  - Microbial contamination in kitchens and bathrooms of rural Cambodian village
      households.
AB  - AIMS: To quantify microbial contamination on kitchen and bathroom surfaces
      (fomites) in rural Cambodian homes and to compare these concentrations to similar
      data from the United States and Japan. METHODS AND RESULTS: This study monitored
      the numbers of faecal coliforms (i.e. thermotolerant coliforms), total coliforms,
      Escherichia coli and heterotrophic plate count bacteria on household surfaces in
      a rural village of Cambodia. Faecal coliform levels in Cambodia were highest on
      moist locations such as the plastic ladle used for sink water, the toilet seat
      surface and the cutting board surface with 100-fold higher levels of faecal
      coliform bacteria than E. coli and 100-fold higher levels of faecal coliforms
      than the US and Japanese studies. CONCLUSIONS: A single public health
      intervention barrier, such as an improved latrine, is only partially effective
      for household sanitation. For complete sanitation, multiple environmental
      barriers may be necessary. These barriers occur in a house constructed with
      easily washable surfaces, a chlorinated water distribution system, house climate
      control and cleaning product availability. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Results of this study can be used to emphasize the importance of increasing
      household environmental sanitation barriers.

PMID- 21198694
TI  - Decontamination efficacy against Mycoplasma.
AB  - AIMS: Mycoplasma is minute bacteria that can be found ubiquitously in the
      environment and also in human, animal and plant tissues. In addition to their
      public health importance as aetiological agents of infections and possible
      association with certain cancers, mycoplasma is a major contamination concern in
      biotechnology. These bacterial cells are very small, can form biofilms and
      survive for extended periods of time when dried onto surfaces. Despite these
      concerns, there is little information concerning their resistance to currently
      used disinfection methods. The objective of this study was to evaluate commonly
      used biocidal treatments against three representative mycoplasma species. METHODS
      AND RESULTS: Mycoplasma was dried onto stainless steel coupons and exposed to
      decontamination products. All strains survived drying and any significant
      viability loss because of the test method (including neutralization), as
      demonstrated by a <=0.5 log(10) for each tested species. The quaternary ammonium
      compound (QAC) tested presented poor efficacy, whereas 70% ethanol was fully
      efficient with complete inactivation after 5-min exposure. Alkaline cleaner
      formulations presented increasing efficacy when tested at 0.2, 0.4 and 0.8%
      concentrations, with complete kill observed at 0.8% of two products tested.
      Decontamination with vaporized (gaseous) hydrogen peroxide (VHP) was very
      efficient at concentrations used for room and small enclosures decontamination
      (180-1200 ppm with various time exposures), as well as for device sterilization
      applications. CONCLUSIONS: Ethanol and alkaline detergent formulations were
      particularly efficient against mycoplasma, but a QAC formulation was not. VHP in
      room disinfection and device sterilization applications was effective against all
      mycoplasma species tested. SIGNIFICANCE AND IMPACT OF THE STUDY: Mycoplasma can
      provide resistance to environmental factors (such as drying) and disinfectants.
      Further studies are required to confirm the effectiveness of other disinfectants
      and the mechanisms of mycoplasma resistance.

PMID- 21198695
TI  - Protection of red snapper (Lutjanus sanguineus) against Vibrio alginolyticus with
      a DNA vaccine containing flagellin flaA gene.
AB  - AIMS: The main aims of this study were to construct a DNA vaccine containing
      flagellin flaA gene from Vibrio alginolyticus strain HY9901 and to explore the
      potential application of pcDNA-flaA as a DNA vaccine candidate for red snapper
      (Lutjanus sanguineus). METHODS AND RESULTS: Plasmid DNA encoding flagellin flaA
      gene (designated as pcDNA-flaA) was used as a DNA vaccine to immunize red
      snapper. The distribution, expression and immunoprotection of the DNA vaccine
      were analysed in tissues of the red snapper by PCR, RT-PCR and challenge test.
      PCR results indicated that pcDNA-flaA distributed in liver, spleen, kidney, gill
      and injection site muscle at 7-28 days after vaccination. RT-PCR results
      indicated that the flaA gene was expressed in all above tissues of vaccinated
      fish at 7-28 days after vaccination. In addition, fish receiving the DNA vaccine
      developed a protective response to live V. alginolyticus challenge 28 days post
      inoculation, the relative per cent survival (RPS) was 88%. CONCLUSIONS: This
      study showed that injection of pcDNA-flaA induced an efficient, systemic and
      antigen-specific immune response in red snapper, which makes it an effective
      vaccine candidate against V. alginolyticus infection. SIGNIFICANCE AND IMPACT OF
      THE STUDY:   The finding that red snapper does adequately respond to pcDNA-flaA
      intramuscular injection makes pcDNA-flaA a promising candidate for DNA vaccine
      treatment. Furthermore, the availability of red snapper for foreign gene
      expression represents a useful model to develop effective prophylactic strategies
      and opens new perspectives for the treatment of bacterial pathogens of marine
      cultured fish.

PMID- 21198696
TI  - Meta-analysis of results from quantitative trait loci mapping studies on pig
      chromosome 4.
AB  - Meta-analysis of results from multiple studies could lead to more precise
      quantitative trait loci (QTL) position estimates compared to the individual
      experiments. As the raw data from many different studies are not readily
      available, the use of results from published articles may be helpful. In this
      study, we performed a meta-analysis of QTL on chromosome 4 in pig, using data
      from 25 separate experiments. First, a meta-analysis was performed for individual
      traits: average daily gain and backfat thickness. Second, a meta-analysis was
      performed for the QTL of three traits affecting loin yield: loin eye area,
      carcass length and loin meat weight. Third, 78 QTL were selected from 20 traits
      that could be assigned to one of three broad categories: carcass, fatness or
      growth traits. For each analysis, the number of identified meta-QTL was smaller
      than the number of initial QTL. The reduction in the number of QTL ranged from
      71% to 86% compared to the total number before the meta-analysis. In addition,
      the meta-analysis reduced the QTL confidence intervals by as much as 85% compared
      to individual QTL estimates. The reduction in the confidence interval was greater
      when a large number of independent QTL was included in the meta-analysis. Meta
      QTL related to growth and fatness were found in the same region as the FAT1
      region. Results indicate that the meta-analysis is an efficient strategy to
      estimate the number and refine the positions of QTL when QTL estimates are
      available from multiple populations and experiments. This strategy can be used to
      better target further studies such as the selection of candidate genes related to
      trait variation.

PMID- 21198697
TI  - Genomic regions associated with antibody response to sheep red blood cells in the
      chicken.
AB  - F(1) and F(2) populations were generated by crossing two lines of chickens
      divergently selected from a common founder population for 32 generations for
      either high or low antibody response 5 days post-injection of a non-pathogenic
      antigen, sheep red blood cells (SRBCs). The number of loci with major effects on
      day 5 SRBC titers was estimated to be more than 7 in this population. There was a
      significant association between MHC haplotype and day 5 antibody titers as well
      as body weight at sexual maturity. A significant difference between reciprocal
      F(2) crosses for both 5- and 12-day antibody titers suggests that sex chromosome
      and/or parent of origin effects on autosomal loci have an important role in
      immune response. A single marker-trait association analysis on 1024 genetic
      markers and 128 F(2) individuals detected 11 genomic regions associated with
      antibody response traits and 17 regions associated with body weight gain. Several
      of the genomic regions identified as being associated with antibody response have
      been described previously, while novel regions associated with antibody response
      were identified on chromosomes 11 and 24. Based on the lack of overlap of the
      regions associated with body weight and antibody response, we conclude that while
      these phenotypes are inversely correlated in the selected lines, they are
      controlled by distinct genetic loci and may be reflective of intense selection
      pressure on loci affecting the partitioning of nutrients between the immune
      system and growth pathways.

PMID- 21198698
TI  - Exploration of relationships between production and fertility traits in dairy
      cattle via association studies of SNPs within candidate genes derived by
      expression profiling.
AB  - The objective of this work was to integrate findings from functional genomics
      studies with genome-wide association studies for fertility and production traits
      in dairy cattle. Association analyses of production and fertility traits with
      SNPs located within or close to 170 candidate genes derived from two gene
      expression studies and from the literature were performed. Data from 2294
      Holstein bulls genotyped for 39557 SNPs were used. A total of 111 SNPs were
      located on chromosomal segments covered by a candidate gene. Allele substitution
      effects for each SNP were estimated using a mixed model with a fixed effect of
      marker and a random polygenic effect. Assumed covariance was derived either from
      marker or from pedigree information. Results from the analysis with the kinship
      matrix built from marker genotypes were more conservative than from the analysis
      with the pedigree-derived relationship matrix. From sixteen SNPs with significant
      effects on both classes of traits, ten provided evidence of an antagonistic
      relationship between productivity and fertility. However, we found four SNPs with
      favourable effects on fertility and on yield traits, one SNP with favourable
      effects on fertility and percentage traits, and one SNP with antagonistic effects
      on two fertility traits. While most quantitative genetic studies have proven
      genetic antagonisms between yield and functional traits, improvements in both
      production and functionality may be possible when focusing on a few relevant
      SNPs. Investigations combining input from quantitative genetics and functional
      genomics with association analysis may be applied for the identification of such
      SNPs.

PMID- 21198699
TI  - Infliximab rescue therapy in steroid-refractory ulcerative colitis: is more
      really more?

PMID- 21198700
TI  - Tacrolimus: rescue therapy or experimental drug for severe ulcerative colitis?

PMID- 21198702
TI  - Midodrine and furosemide-induced natriuresis in cirrhotics with ascites.

PMID- 21198703
TI  - Systematic review: Clostridium difficile and inflammatory bowel disease.
AB  - BACKGROUND: There is increasing concern about the apparently rising incidence and
      worsening outcome of Clostridium difficile infection (CDI) associated with
      inflammatory bowel disease (IBD). We have systematically reviewed the literature
      to evaluate the incidence, risk factors, endoscopic features, treatment and
      outcome of CDI complicating IBD. AIM: To systematically review: clostridium
      difficile & inflammatory bowel disease. METHODS: Structured searches of Pubmed up
      to September 2010 for original, cross-sectional, cohort and case-controlled
      studies were undertaken. RESULTS: Of 407 studies, 42 met the inclusion criteria:
      their heterogeneity precluded formal meta-analysis. CDI is commoner in active
      IBD, particularly ulcerative colitis, than in controls. Certainty about a
      temporal trend to its increasing incidence in IBD is compromised by possible
      detection bias and miscoding. Risk factors include immunosuppressants and
      antibiotics, the latter less commonly than in controls. Endoscopy rarely shows
      pseudomembranes and is unhelpful for diagnosing CDI in IBD. There are no
      controlled therapeutic trials of CDI in IBD. In large studies, outcome of CDI in
      hospitalised IBD patients appears worse than in controls. CONCLUSIONS: The
      complication of IBD by Clostridium difficile infection has received increasing
      attention in the past decade, but whether its incidence is really increasing or
      its outcome worsening remains unproven. Therapeutic trials of Clostridium
      difficile infection in IBD are lacking and are needed urgently.

PMID- 21198704
TI  - The natural history of acute hepatitis C: clinical presentation, laboratory
      findings and treatment outcomes.
AB  - BACKGROUND: Acute hepatitis C has variable modes of presentation and frequently
      results in chronic infection. Its optimal management has yet to be defined. AIM:
      To establish natural history and complications of treatment of acute hepatitis C.
      METHODS: Data from all patients presenting with acute hepatitis C to the National
      Institutes of Health between 1994 and 2007 were reviewed. RESULTS: Twenty-five
      patients were identified. Symptoms were reported by 80% and jaundice by 40%.
      Aminotransferase levels and hepatitis C virus (HCV) RNA levels fluctuated
      greatly; 18% of patients were intermittently negative for HCV RNA. Five patients
      recovered spontaneously whereas 20 developed chronicity or received interferon
      based therapy during the acute phase. Among 15 patients treated during the acute
      phase with peginterferon with or without ribavirin for 24 weeks, all became HCV
      RNA negative within 4-8 weeks, and all except two (HIV-positive) achieved a
      sustained virological response. Side effects (particularly psychiatric) were
      common and limited treatment in 30%. CONCLUSIONS: Among 25 patients with acute
      HCV infection, fluctuating illness was common and spontaneous recovery occurred
      in only 20%. Anti-viral treatment with a 24-week course of peginterferon and
      ribavirin was highly effective, but marked by frequent and severe side effects.

PMID- 21198705
TI  - Weakly acidic refluxes have a major role in the pathogenesis of proton pump
      inhibitor-resistant reflux oesophagitis.
AB  - BACKGROUND: In patients with heartburn that persists despite proton pump
      inhibitor (PPI) therapy, reflux oesophagitis is found rarely, and its
      pathogenesis has been scarcely studied. AIM: To assess reflux parameters by
      impedance-pH monitoring in PPI-resistant reflux oesophagitis. METHODS: Impedance
      pH monitoring was performed on PPI therapy in patients with symptomatic reflux
      oesophagitis detected despite standard or high-dose PPI therapy of at least 8
      week duration. RESULTS: Twenty patients, ten on once daily and ten on twice daily
      PPI regimens, were studied. The gastric acid exposure time (per cent time pH <4)
      ranged from 10% to 81% and was >30% in 70% of cases, but the oesophageal acid
      exposure time (per cent time pH <4) was abnormal in 20% of patients only. The
      number of acid, weakly acidic and weakly alkaline refluxes was abnormal in 25%,
      100% and 15% of patients, respectively. CONCLUSIONS: Weakly acidic refluxes were
      above the normal range in all cases, whereas acid reflux parameters and weakly
      alkaline refluxes were normal in the vast majority of cases. Gastric acid
      secretion, with consequent intra-gastric pepsins activation, persists despite
      ongoing PPI therapy and activated pepsins may well be present in weakly acidic
      refluxes. As activated pepsins maintain their proteolytic activity in a weakly
      acidic environment, they may be responsible for mucosal damage. We conclude that
      weakly acidic refluxes have a major role in the pathogenesis of PPI-resistant
      reflux oesophagitis. Therapeutic interventions in patients with PPI-resistant
      reflux oesophagitis should be tailored on the basis of impedance-pH-monitoring
      results.

PMID- 21198706
TI  - Application of the WHO fracture risk assessment tool (FRAX) to predict need for
      DEXA scanning and treatment in patients with inflammatory bowel disease at risk
      of osteoporosis.
AB  - BACKGROUND: Although patients with inflammatory bowel disease (IBD) are at
      increased risk of osteoporosis, low bone mineral density (BMD) alone confers only
      a modest increase in risk of fracture. The FRAX score, developed by the WHO, is a
      free web-based clinical scale assessing the 10-year fracture risk and need for
      lifestyle advice/reassurance, dual X-ray absorptiometry (DEXA) scanning or
      preventive treatment. AIM: To assess the accuracy of pre-BMD FRAX scores in
      identifying at risk IBD patients needing BMD measurement (intermediate risk)
      and/or therapy (high risk). METHODS: We calculated FRAX scores retrospectively in
      116 consecutive IBD out-patients (81 Crohn's disease, 35 ulcerative colitis), who
      were having DEXA scans in 2005-2009 because they were considered at risk of
      osteoporosis. RESULTS: On DEXA scans, 47% (38/81) and 12% (10/81) patients with
      Crohn's disease were osteopaenic and osteoporotic, respectively; equivalent
      figures for patients with UC were 34% (12/35) and 14% (5/35). The clinical FRAX
      score alone, when compared with the FRAX score including the BMD result, had a
      sensitivity of 100% (95% CI: 70-100%), specificity of 40% (95% CI: 31-50%),
      positive predictive value of 16% (95% CI: 9-27%) and negative predictive value of
      100% (95% CI: 90-100%) in identifying those patients needing BMD measurement
      (intermediate risk) or preventive therapy (high risk). CONCLUSIONS: In patients
      with IBD perceived to be at risk of osteoporosis and/or osteopaenia, the clinical
      FRAX score alone can predict accurately the risk of osteoporotic fracture, and
      thereby reduce the need for DEXA scans and unnecessary anti-osteoporosis
      treatment.

PMID- 21198707
TI  - Review article: chronic hepatitis B - anti-viral or immunomodulatory therapy?
AB  - BACKGROUND: First-line treatment options for chronic hepatitis B (CHB) consist of
      nucleos(t)ide analogues with a high barrier to resistance (entecavir and
      tenofovir) or the immunomodulatory agent peginterferon (PEG-IFN). The optimal
      choice for individual patients remains controversial. AIM: To review treatment
      options for CHB, with a focus on deciding between prolonged nucleos(t)ide
      analogue therapy or a finite course of PEG-IFN. METHODS: A comprehensive
      literature search was undertaken. RESULTS: Long-lasting, treatment-maintained
      suppression of hepatitis B virus (HBV) DNA without resistance is achievable in
      most patients by entecavir or tenofovir. A sustained off-treatment response is,
      however, unlikely and long-term therapy must be anticipated. PEG-IFN offers a
      higher rate of sustained response in a subgroup of patients, but is frequently
      complicated by side effects. Pre-treatment predictors of response, including HBV
      genotype, alanine aminotransferase and HBV DNA levels, aid in selecting patients
      for PEG-IFN therapy. Furthermore, on-treatment markers such as quantitative
      hepatitis B surface antigen may be applied to identify nonresponders early during
      the PEG-IFN treatment course, thereby preventing unnecessary treatment.
      CONCLUSIONS: Both nucleos(t)ide analogues and PEG-IFN can be prescribed as first
      line treatment options for CHB. However, PEG-IFN should only be considered for
      patients with a high chance of response based on pre-treatment and on-treatment
      factors.

PMID- 21198709
TI  - Endogenously released opioids mediate meal-induced gastric relaxation via
      peripheral mu-opioid receptors.
AB  - BACKGROUND: The centrally acting mu-opioid receptor antagonist naloxone inhibits
      meal-induced gastric accommodation. AIM: To study the role of peripheral mu
      opioid receptors in the regulation of gastric tone and food intake by comparing
      the effects of naloxone with the peripherally restricted mu-opioid receptor
      antagonist methylnaltrexone. METHODS: Methylnaltrexone (12 mg s.c.), naloxone (20
      MUg/kg/h intravenous infusion after 0.4 mg bolus) and placebo were studied in 23
      healthy volunteers. Gastric volume was recorded using an intragastric bag held at
      constant pressure connected to a barostat, with administration of a nutrient
      drink after 30 min. Pressure in the stomach was measured during intragastric
      nutrient drink infusion until the volunteers scored maximal satiation. RESULTS:
      Methylnaltrexone inhibited significantly the volume increase after food intake as
      assessed with the barostat (P < 0.01). During nutrient drink infusion the
      intragastric pressure significantly decreased as compared with the preprandial
      pressure after placebo treatment. Both methylnaltrexone and naloxone
      significantly inhibited this intragastric pressure decrease (P < 0.001 and P <
      0.05, respectively). Volunteers scored maximal satiation after 979 +/- 96, 958 +/
      84 and 1124 +/- 107 mL nutrient drink infused (for naloxone, methylnaltrexone
      and placebo treatment, respectively; P < 0.05). CONCLUSIONS: These results
      indicate that endogenous opioids mediate gastric accommodation and satiation via
      peripheral mu-opioid receptors. Effects were less pronounced after naloxone
      treatment, which indicates that centrally involved mu-opioid receptors mediate an
      opposing effect.

PMID- 21198710
TI  - Longterm persistence of proteolytic activities in frass of Blattella germanica
      increases its allergenic potential.
AB  - Chromogenic microplate assays in 96 wells were used to determine the stability of
      enzyme activity in frass of Blattella germanica (Blattodea: Blattellidae). Frass
      samples were exposed to controlled conditions [temperature 15-35  degrees C
      and/or 53-100% relative humidity (RH)] and to household conditions (apartment).
      Exposure times were 0 (control), 90, 183 and 276 days. Starch digestion and
      cellulolytic activities decreased during exposure. Non-specific proteolytic
      activities were affected by changes in selective proteolytic activities.
      Activities towards AAPpNA and SA(3) pNA strongly increased at 100% RH, indicating
      the possible influence of microorganisms growing on frass. Activities towards
      BApNA and ArgpNA decreased with increasing decomposition time, whereas activity
      towards ZRRpNA was not influenced by exposure time. The largest decrease in
      activities towards ArgpNA and BApNA occurred at temperatures of 15  degrees C, 30
      degrees C and 35  degrees C and at 100% RH. Activities towards BApNA and ZRRpNA
      were very stable under different temperature and RH conditions; this was
      confirmed by findings showing that these activities were stable in the
      experimental apartment. In comparison with the control, activities towards ZRRpNA
      and BApNA after 276 days decreased by 1% and 19%, respectively. The longterm
      persistence of proteolytic activities in cockroach frass increases their
      allergenic hazard potential.

PMID- 21198711
TI  - Evaluation of species distribution model algorithms for fine-scale container
      breeding mosquito risk prediction.
AB  - The present work evaluates the use of species distribution model (SDM) algorithms
      to classify high densities of small container-breeding Aedes mosquitoes (Diptera:
      Culicidae) on a fine scale in the Bermuda Islands. Weekly ovitrap data collected
      by the Department of Health, Bermuda for the years 2006 and 2007 were used for
      the models. The models evaluated included the algorithms Bioclim, Domain, GARP
      (genetic algorithm for rule-set prediction), logistic regression and MaxEnt
      (maximum entropy). Models were evaluated according to performance and robustness.
      The area under the receiver operating characteristic curve was used to evaluate
      each model's performance, and robustness was assessed according to the spatial
      correlation between classification risks for the two datasets. Relative to the
      other algorithms, logistic regression was the best and MaxEnt the second best
      model for classifying high-risk areas. We describe the importance of covariables
      for these two models and discuss the utility of SDMs in vector control efforts
      and the potential for the development of scripts that automate the task of
      creating risk assessment maps.

PMID- 21198708
TI  - Systematic review: the diagnosis and staging of non-alcoholic fatty liver disease
      and non-alcoholic steatohepatitis.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become the most
      prevalent cause of liver disease in Western countries. The development of non
      alcoholic steatohepatitis (NASH) and fibrosis identifies an at-risk group with
      increased risk of cardiovascular and liver-related deaths. The identification and
      management of this at-risk group remains a clinical challenge. AIM: To perform a
      systematic review of the established and emerging strategies for the diagnosis
      and staging of NAFLD. METHODS: Relevant research and review articles were
      identified by searching PubMed, MEDLINE and EMBASE. RESULTS: There has been a
      substantial development of non-invasive risk scores, biomarker panels and
      radiological modalities to identify at-risk patients with NAFLD without recourse
      to liver biopsy on a routine basis. These modalities and algorithms have improved
      significantly in their diagnosis and staging of fibrosis and NASH in patients
      with NAFLD, and will likely impact on the number of patients undergoing liver
      biopsy. CONCLUSIONS: Staging for NAFLD can now be performed by a combination of
      radiological and laboratory techniques, greatly reducing the requirement for
      invasive liver biopsy.

PMID- 21198712
TI  - A new transmission risk index for human African trypanosomiasis and its
      application in the identification of sites of high transmission of sleeping
      sickness in the Fontem focus of southwest Cameroon.
AB  - A new index for the risk for transmission of human African trypanosomiasis was
      developed from an earlier index by adding terms for the proportion of tsetse
      infected with Trypanosoma brucei gambiense group 1 and the contribution of
      animals to tsetse diet. The validity of the new index was then assessed in the
      Fontem focus of southwest Cameroon. Averages of 0.66 and 4.85 Glossina palpalis
      palpalis (Diptera: Glossinidae) were caught per trap/day at the end of one rainy
      season (November) and the start of the next (April), respectively. Of 1596 tsetse
      flies examined, 4.7% were positive for Trypanosoma brucei s.l. midgut infections
      and 0.6% for T. b. gambiense group 1. Among 184 bloodmeals identified, 55.1% were
      from pigs, 25.2% from humans, 17.6% from wild animals and 1.2% from goats. Of the
      meals taken from humans, 81.5% were taken at sites distant from pigsties. At the
      end of the rainy season, catches were low and similar between biotopes distant
      from and close to pigsties, but the risk for transmission was greatest at sites
      distant from the sties, suggesting that the presence of pigs reduced the risk to
      humans. At the beginning of the rainy season, catches of tsetse and risk for
      transmission were greatest close to the sties. In all seasons, there was a strong
      correlation between the old and new indices, suggesting that both can be used to
      estimate the level of transmission, but as the new index is the more
      comprehensive, it may be more accurate.

PMID- 21198713
TI  - Molecular taxonomy of members of the Anopheles hyrcanus group from Thailand and
      Indonesia.
AB  - During studies of malaria vectors in Indonesia and Thailand, several specimens
      identified by field staff as members of the Anopheles barbirostris group
      (Diptera: Culicidae) were found to belong to the Anopheles hyrcanus group, as
      shown by marked differences in the size of the nuclear rDNA second internal
      transcribed spacer (ITS2) between the barbirostris (~1500 bp) and hyrcanus (~600
      bp) groups. Identification of the species concerned required a more detailed
      study of ITS2 sequences and subunit I of the mitochondrial DNA cytochrome oxidase
      gene (COI). A phylogenetic analysis, based on Bayesian methods, revealed that the
      hyrcanus group specimens comprised five distinct clades, two of which
      corresponded with known species, Anopheles peditaeniatus and Anopheles sinensis.
      The remaining specimens formed three additional clades, for which there are no
      similar sequences in GenBank and which cannot be linked to previously described
      species. The misidentification of hyrcanus group species has important
      implications for malaria vector control; more comprehensive studies employing
      gene sequences are required to clarify the number of species in the group, their
      distribution and vector status.

PMID- 21198714
TI  - Spatio-temporal distribution of tsetse and other biting flies in the Mouhoun
      River basin, Burkina Faso.
AB  - In the Mouhoun River basin, Burkina Faso, the main vectors of African animal
      trypanosomoses are Glossina palpalis gambiensis Vanderplank and Glossina
      tachinoides Westwood (Diptera: Glossinidae), both of which are riverine tsetse
      species. The aim of our study was to understand the impact of landscape
      anthropogenic changes on the seasonal dynamics of vectors and associated
      trypanosomosis risk. Three sites were selected on the basis of the level of
      disturbance of tsetse habitats and predominant tsetse species: disturbed (Boromo,
      for G. tachinoides) and half-disturbed (Douroula for G. tachinoides and Kadomba
      for G. p. gambiensis). At each of these sites, seasonal variations in the
      apparent densities of tsetse and mechanical vectors and tsetse infection rates
      were monitored over 17 months. Tsetse densities differed significantly between
      sites and seasons. Of 5613 captured tsetse, 1897 were dissected; 34 of these were
      found to be infected with trypanosomes. The most frequent infection was
      Trypanosoma vivax (1.4%), followed by Trypanosoma congolense (0.3%) and
      Trypanosoma brucei (0.05%). The mean physiological age of 703 tsetse females was
      investigated to better characterize the transmission risk. Despite the
      environmental changes, it appeared that tsetse lived long enough to transmit
      trypanosomes, especially in half-disturbed landscapes. A total of 3021 other
      biting flies from 15 species (mainly Tabanidae and Stomoxyinae) were also caught:
      their densities also differed significantly among sites and seasons. Their
      relative importance regarding trypanosome transmission is discussed; the
      trypanosomosis risk in cattle was similar at all sites despite very low tsetse
      densities (but high mechanical vector densities) in one of them.

PMID- 21198715
TI  - Quadrivalent human papillomavirus (HPV) vaccine: a review of safety, efficacy,
      and pharmacoeconomics.
AB  - WHAT IS KNOWN AND BACKGROUND: The introduction of vaccines has lead to a
      significant reduction in morbidity and mortality from diseases such as measles,
      rubella and poliomyelitis, as well as the eradication of smallpox (Ertl HC, Xiang
      Z (1996) The Journal of Immunology, 156, 3579-3582). A recent vaccine approved by
      the Food and Drug Administration (FDA) is the recombinant quadrivalent human
      papillomavirus (HPV) vaccine (Merck, Gardasil(r)). Concerns raised with this
      preventive measure include safety and efficacy issues as well as the financial
      implications. Furthermore, the use of the vaccine in women outside the currently
      approved age ranges and in adolescent boys and men has also been a source of
      debate. OBJECTIVE: A review of two licensed HPV vaccines (Gardasil, Merck and
      Cervarix, GalxoSmithKline) in the light of these issues. METHODS: Literature
      searches were conducted using the MEDLINE (1966-December 2008) and PubMed
      databases in addition to the Centers for Disease Control and Prevention website.
      Bibliographies of selected references were also evaluated for relevant articles.
      Published guidelines and press releases were utilized as were the manufacturer's
      package inserts. The collection of information for this review was limited to the
      most recently available human data. RESULTS AND DISCUSSION: The HPV quadrivalent
      vaccine has been effective in the management of HPV by preventing vaccine subtype
      related persistent infection and precancerous lesions as evidenced by numerous
      clinical trials. It is also regarded as a generally safe and well-tolerated
      vaccine, based on an assessment of reported adverse events submitted through
      governmental databases and analyzed by independent researchers. The majority of
      adverse events were non-serious and the vaccine has not been conclusively
      implicated with serious events. The FDA continues to focus on routine post
      marketing surveillance monitoring of reported adverse events. The bivalent
      vaccine has also been shown to be effective in reported trials. Its adverse
      effect profile also appears acceptable. WHAT IS NEW AND CONCLUSION: The HPV
      vaccines appear safe and effective. Additional clinical research on the vaccines
      on women outside the currently approved age ranges and in males is necessary.
      Studies on longer-term outcomes, including cervical cancer and the emergence of
      new viral genotypes are also necessary.

PMID- 21198716
TI  - An overview of the metabolic effects of rimonabant in randomized controlled
      trials: potential for other cannabinoid 1 receptor blockers in obesity.
AB  - WHAT IS KNOWN AND OBJECTIVE: Rimonabant, a cannabinoid receptor blocker, has
      recently been used in clinical practice for weight loss and weight maintenance.
      Our aim was to review the results of trials of the drug in relation to weight
      loss and maintenance, and its impact on cardio-metabolic risk factors. METHODS:
      Randomized controlled trials with rimonabant were selected, through a Medline
      search, using the terms: rimonabant, endocannabinoid antagonist and obesity.
      Reports of studies on large numbers of patients and covering the topics related
      to this review were included. RESULTS AND DISCUSSION: In all the trials, there
      was a considerable reduction in body weight in subjects taking 20 mg rimonabant
      daily varying from 2.6 to 6.3 kg (placebo-subtracted changes). Rimonabant was
      also associated with haemoglobin A(1c) (HbA(1c) ) reduction. In the Rimonabant in
      obesity (RIO)-diabetes study, diabetic patients taking metformin or
      sulphonylureas showed decrease in HbA(1c) levels by 0.5-0.6 +/- 0.8% when
      rimonabant was added, whereas in the Serenade trial patients with untreated
      diabetes showed a reduction in HbA(1c) of 0.8% vs. 0.3% with placebo. Similar
      results were obtained in diabetic patients under insulin treatment. The lipidemic
      profile also improved in patients taking rimonabant 20 mg daily; levels of high
      density lipoprotein cholesterol (HDL-c) increased significantly while levels of
      triglycerides (TRG) decreased in all trials, and positive effects were also
      observed in patients with atherogenic or untreated dyslipidaemia. In all the RIO
      studies, prevalence of the metabolic syndrome decreased significantly. In
      addition, patients treated with 20 mg rimonabant daily exhibited increase in
      adiponectin. The metabolic changes observed were partly independent of the weight
      loss and could be attributed to independent peripheral effect of rimonabant. All
      these beneficial metabolic effects of rimonabant could lead to progress in the
      prevention of cardiovascular disease. However, in all the trials the incidence of
      adverse events leading to discontinuation was greater in the rimonabant treated
      patients than placebo, mainly because of psychiatric disorders (depression and
      anxiety), nausea and dizziness. WHAT IS NEW AND CONCLUSION: Rimonabant is
      effective in reducing weight in the obese but may lead to intolerable adverse
      effects most notably psychiatric effects, which make it unsuitable for routine
      use. However, the drug provides useful proof of principle for this approach to
      weight loss. Novel cannabinoid type 1 receptor blockers with selectivity for
      peripheral receptors, may achieve similar metabolic results with decreased
      prevalence of psychiatric adverse effects.

PMID- 21198717
TI  - Management of relapsed or refractory multiple myeloma in French hospitals and
      estimation of associated direct costs: a multi-centre retrospective cohort study.
AB  - WHAT IS KNOWN AND BACKGROUND:  For relapsed or refractory multiple myeloma
      (RRMM), a series of novel agents (thalidomide, bortezomib and lenalidomide) has
      emerged during the latest decade, but their use in routine clinical practice is
      not well documented as well as the cost of RRMM. OBJECTIVE: Our aim is to review
      the therapeutic management of such patients in France and to estimate the
      associated costs. METHODS: A retrospective cohort study, based on chart reviews,
      was conducted in French Haematology Departments over the period 2004-2007 and the
      associated direct costs estimated. RESULTS: One hundred and two patients with a
      relapse after first-line therapy were selected from five centres. The average
      follow-up from diagnosis or the date of first relapse to death or to the latest
      news was respectively 56.25 and 23.53 months. Novel agents were used in 73% of
      all cases, and in all cases of first relapse. Thalidomide and bortezomib were
      respectively the most frequently used second-line (57%) and third-line treatments
      (44%). The average number of lines of treatment received per patient as from
      first relapse was 2.75 (min 1; max 8) and the mean direct cost per month was
      estimated at 3130 ? after the first relapse. This cost was represented in greater
      part by the cost of chemotherapy drugs (66%). WHAT IS NEW AND CONCLUSION: The use
      of novel agents such as thalidomide, bortezomib and lenalidomide for RRMM is
      highly prevalent in France from the first relapse. The associated medical cost is
      substantial mainly due to the cost of the new agents.

PMID- 21198718
TI  - Inappropriate prescribing in older residents of Australian care homes.
AB  - WHAT IS KNOWN AND OBJECTIVE: The incidence of inappropriate prescribing is higher
      amongst the older age group than the younger population. Inappropriate
      prescribing potentially leads to drug-related problems such as adverse drug
      reactions. We aimed to determine the prevalence of inappropriate prescribing in
      residents of Tasmanian (Australia) residential care homes using Beers and McLeod
      criteria. METHODS: Patient demographics, medical conditions and medications were
      collected from medical records. The patients who fulfilled either Beers or McLeod
      criteria were identified and the characteristics of these patients were then
      compared. RESULTS: Data for 2345 residents were collected between 2006 and 2007.
      There were 1027 (43.8%) patients prescribed at least one inappropriate
      medication. Beers criteria identified more patients (828 patients, 35.3%) as
      being prescribed inappropriate medication compared with McLeod criteria (438
      patients, 18.7%). Patients taking psychotropic medication/s, more than six
      medications or diagnosed with five or more medical conditions were more likely to
      be prescribed an inappropriate medication (P<0.001). The most frequently
      identified inappropriate medications included benzodiazepines, amitriptyline,
      oxybutynin and non-steroidal anti-inflammatory drugs. WHAT IS NEW AND CONCLUSION:
      Inappropriate prescribing, as defined by either Beers criteria or McLeod
      criteria, is relatively common in Australian nursing homes. The prevalence of
      inappropriate prescribing, and factors influencing it, are consistent with other
      countries. Both Beers and McLeod criteria are a general guide to prescribing, and
      do not substitute for professional judgment.

PMID- 21198719
TI  - The efficacy and toxicity of two dosing-regimens of amikacin in neonates with
      sepsis.
AB  - WHAT IS KNOWN AND OBJECTIVE: Neonatal sepsis is one of the most common reasons
      for admission to neonatal units in developing countries. Aminoglycosides widely
      used in its treatment are usually administered two or three times a day. Less
      frequent doing may be more convenient and as effective. We aim to compare the
      efficacy and safety (nephrotoxicity) of once daily vs. twice daily dosing of
      amikacin in neonates with suspected or proven sepsis and report on the drug's
      pharmacokinetics in these subjects. METHODS: Thirty neonates of gestational age
      >= 36 weeks and body weight >= 2500 g with suspected or proven sepsis were
      randomized to receive amikacin either at a dose of 15 mg/kg once per day; group I
      (n = 15), or a dose of 7.5 mg/kg twice per day, group II (n = 15). All neonates
      received classical treatment of sepsis including antibiotics, hemodynamic
      support, inotropic support based on blood pressure levels and size of the heart
      in chest X-ray, if needed. Amikacin was infused over 1 h. Peak and trough serum
      samples for amikacin were measured for all infants at steady state.
      Nephrotoxicity was assessed by serum creatinine and urinary N-acetyl beta-D
      glucosaminidase before and 7 days after therapy. Clinical efficacy was compared
      using both observation of clinical status and normalization of laboratory tests.
      RESULTS: All the patients in group I had achieved a trough level < 10 MUg/mL and
      two patients had trough concentration > 10 MUg/mL in group II. No significant
      difference between group I and group II in either baseline or day 7 serum
      creatinine was demonstrated (P >0.05). No significant difference was found
      between the two groups in clinical efficacy or renal toxicity. The calculated
      pharmacokinetic parameters were in group I and II, respectively: clearance = 63.8
      +/- 15.9 mL/kg/h and 73.5 +/- 18.1 mL/kg/h; volume of distribution = 0.54 +/-
      0.09 L/kg and 0.61 +/- 0.13 L/kg, half-life =6.1 +/- 1.0 h and 5.95 +/- 1.1 h.
      WHAT IS NEW AND CONCLUSION: As expected, amikacin given once every 24 h to septic
      neonates of >= 36 weeks of gestation achieved higher peak levels and lower trough
      concentrations than the twice daily regimen. Treatment with once daily regimen
      did not lead to more nephrotoxicity than with a twice-daily regimen, and showed
      comparable efficacy.

PMID- 21198720
TI  - Effects of vitamin E supplementation on glycaemic control in type 2 diabetes:
      systematic review of randomized controlled trials.
AB  - WHAT IS KNOWN AND OBJECTIVE: Lowering haemoglobin A(1c) (HbA(1c)) has clearly
      been shown to reduce microvascular complications of diabetes and possibly
      macrovascular disease and vitamin E has been suggested as a possibly useful
      intervention. Our aim is to evaluate the effect of vitamin E supplementation on
      glycaemic control in type 2 diabetes. METHODS: Clinical studies of vitamin E were
      identified from computerized searches of MEDLINE, EMBASE, EBM reviews and the
      Cochrane Library up until November 2008. Historical searches of reference lists
      of relevant articles were also undertaken. To be included in our review, a study
      had to be: (i) a randomized controlled trial comparing vitamin E monopreparation
      against placebo or no treatment in patients with type 2 diabetes, (ii) lasting at
      least 8 weeks, and (iii) reporting glycated haemoglobin or HbA(1c). There was no
      language restriction. Study selection, data extraction and study quality
      assessment were performed by three reviewers with disagreement resolved by
      discussion. Treatment effect was estimated with the mean difference in the
      changes of HbA(1c) from baseline to final assessment between the vitamin E and
      the control groups. RESULTS: Nine trials involving 418 patients were included in
      this review. Vitamin E supplementation did not improve glycaemic control in the
      full set of type 2 diabetes patients. It was effective only in a subgroup of
      patients with inadequate glycaemic control at baseline (HbA(1c) >= 8%) and in
      those whose baseline serum vitamin E levels were below normal ranges. The pooled
      mean difference in the changes of HbA(1c) was -0.58% (95% CI -0.83% to -0.34%; P
      < 0.00001) which was the same for both subgroups of patients. WHAT IS NEW AND
      CONCLUSIONS: The evidence suggests no beneficial effect of vitamin E
      supplementation in improving glycaemic control in unselected patients with type 2
      diabetes. However, HbA(1c) may decrease with vitamin E supplementation in
      patients with inadequate glycaemic control or low serum levels of vitamin E. This
      shows the importance of targeting therapy. Due to the limitations of the
      available evidence, further studies are warranted. Also, the safety and long-term
      benefit of such supplements remain to be determined before its clinical benefit
      can be established unequivocably.

PMID- 21198721
TI  - Prevalent aetiologies of non-therapeutic warfarin anticoagulation in a network of
      pharmacist-managed anticoagulation clinics.
AB  - WHAT IS KNOWN AND OBJECTIVE: There is wide inter-patient and intra-patient
      variability in the pharmacodynamic profile of warfarin. To determine the
      prevailing aetiologies of non-therapeutic warfarin anticoagulation episodes among
      patients currently enrolled in an outpatient anticoagulation clinic and compare
      the relative frequency in which they occur compared to therapeutic
      anticoagulation regimens. METHODS: Prospective, observational cohort study set
      within three pharmacist-managed anticoagulation clinics in a community outpatient
      health system. Patients were included, if they were seen for an office visit
      during the 6-month period from September 2006 to March 2007 and evaluated for the
      presence or absence of 12 investigational factors linked to non-therapeutic
      anticoagulation results. Multivariate stepwise logistic regression performed to
      assess predictive value of each factor. RESULTS: A total of 5817 patient-visits
      were documented producing 2886 (49.6%) non-therapeutic and 2931 (50.4%)
      therapeutic International Normalized Ratio (INR) readings. The most prevalent
      aetiologies linked to non-therapeutic INR results included change in dietary
      vitamin K intake (16.9%, OR 6.4), non-compliance (15.0%, OR 4.9), and initiation
      of anticoagulant therapy (9.9%, OR 2.3). The factor with the highest predictive
      value of non-therapeutic INR results was a change in health status (OR 9.5)
      despite its lower rate of frequency (4.9%). Despite identification of many
      causative factors in this study, 40.2% of non-therapeutic INR readings had no
      known aetiology. In the end, the lack of any study factor was a greater predictor
      of therapeutic anticoagulation (86.2%), than the presence of a study factor was
      for predicting non-therapeutic INR values (51.4%). WHAT IS NEW AND CONCLUSION:
      Change in health status was the strongest predictor of non-therapeutic INR levels
      out of the investigational factors evaluated. Our study demonstrated that there
      are many aetiologies for non-therapeutic INR values that were not explained by
      our investigational factors.

PMID- 21198722
TI  - Stroke risk assessment for atrial fibrillation: hospital-based stroke risk
      assessment and intervention program.
AB  - BACKGROUND: Despite the proven effectiveness of antithrombotic therapy for atrial
      fibrillation (AF), the treatment remains suboptimal. The aim of this study was to
      implement and evaluate a system to improve the appropriate use of antithrombotics
      for stroke prevention in AF utilizing a clinical pharmacist as a stroke risk
      assessor. METHOD: Hospital in-patients with AF were prospectively identified and
      they received a formal stroke risk assessment from a pharmacist. The patients'
      risk of stroke was assessed and documented according to Australian guidelines and
      a recommendation regarding antithrombotic therapy was made to the medical team on
      a specially designed stroke risk assessment form. RESULTS: One hundred and thirty
      four stroke risk assessments were performed during the intervention period. For
      those patients at high risk of stroke and with no contraindication present
      (warfarin-eligible patients), 98% were receiving warfarin on discharge from
      hospital compared to 74% on admission (P < 0.001). Of the 50 (37%) assessments
      that recommended a change of therapy, 44 (88%) resulted in a change in the
      patient's current antithrombotic therapy compared to their admission therapy.
      Thirty (68%) of the assessments resulted in an 'upgrade' to more-effective
      treatment options for example from no therapy to any agent or from aspirin to
      warfarin. DISCUSSION AND CONCLUSION: The pharmacist-led stroke risk assessment
      program resulted in a significant increase in the proportion of patients
      receiving appropriate thromboprophylaxis for stroke prevention in AF. The methods
      used in this study should be evaluated in a larger trial, in multiple hospitals,
      with different pharmacists performing the intervention.

PMID- 21198723
TI  - Driving clinical study efficiency by using a productivity breakdown model:
      comparative evaluation of a global clinical study and a similar Japanese study.
AB  - WHAT IS KNOWN AND OBJECTIVE: A fundamental management imperative of
      pharmaceutical companies is to contain surging costs of developing and launching
      drugs globally. Clinical studies are a research and development (R&D) cost
      driver. The objective of this study was to develop a productivity breakdown
      model, or a key performance indicator (KPI) tree, for an entire clinical study
      and to use it to compare a global clinical study with a similar Japanese study.
      We, thereby, hope to identify means of improving study productivity. METHODS: We
      developed the new clinical study productivity breakdown model, covering
      operational aspects and cost factors. Elements for improving clinical study
      productivity were assessed from a management viewpoint by comparing empirical
      tracking data from a global clinical study with a Japanese study with similar
      protocols. RESULTS: The following unique and material differences, beyond simple
      international difference in cost of living, that could affect the efficiency of
      future clinical trials were identified: (i) more frequent site visits in the
      Japanese study, (ii) head counts at the Japanese study sites more than double
      those of the global study and (iii) a shorter enrollment time window of about a
      third that of the global study at the Japanese study sites. WHAT IS NEW AND
      CONCLUSION: We identified major differences in the performance of the two
      studies. These findings demonstrate the potential of the KPI tree for improving
      clinical study productivity. Trade-offs, such as those between reduction in head
      count at study sites and expansion of the enrollment time window, must be
      considered carefully.

PMID- 21198724
TI  - Stability and compatibility of doxofylline with phentolamine mesilate in 0.9%
      sodium chloride or 5% dextrose injection for intravenous infusion.
AB  - WHAT IS KNOWN AND OBJECTIVE: The use of extemporaneously prepared admixtures of
      drugs must be supported by documentation of their chemical stability. The
      objective was to assess the physical compatibility and the chemical stability of
      doxofylline with phentolamine mesilate in 0.9% sodium chloride or 5% dextrose
      injection for intravenous infusion. METHODS: Total volumes of 20 and 1 mL of
      doxofylline solution and phentolamine mesilate solution, respectively, were added
      to 250 mL polyolefin bags containing 5% dextrose injection or 0.9% sodium
      chloride injection. Bags were stored for 24 h at 20-25  degrees C. Chemical
      compatibility was measures with high-performance liquid chromatography, and
      physical compatibility was determined visually. RESULTS: The samples were clear
      and colourless when viewed in normal fluorescent room light. The pH value and
      particulate content of the admixtures exhibited little change. The retentions of
      the initial concentration of doxofylline and phentolamine mesilate in the
      admixtures were within 97-105%. Doxofylline and phentolamine mesilate were stable
      in 5% dextrose injection or in 0.9% sodium chloride for up to 24 h at 20-25 
      degrees C. WHAT IS NEW AND CONCLUSION: Doxofylline and phentolamine mesilate
      mixed in both 5% dextrose injection and 0.9% sodium chloride injection in 250 mL
      multilayer polyolefin bags at concentrations of 0.74 mg/mL and 36.9 MUg/mL,
      respectively, were stable for up to 24 h at 20-25  degrees C.

PMID- 21198725
TI  - Inhibition of intestinal cholesterol absorption might explain cholesterol
      lowering effect of telmisartan.
AB  - WHAT IS KNOWN AND OBJECTIVE: Telmisartan, an angiotensin II type 1 receptor
      blocker (ARB), acts as a partial agonist for peroxisome proliferator-activated
      receptor-gamma, and thus improves abnormalities of glucose metabolism and
      hypertriglyceridaemia in addition to its documented blood pressure-lowering
      effects. Recently, it has been demonstrated that telmisartan also lowers the
      levels of total cholesterol and low-density lipoprotein (LDL) cholesterol levels.
      This study was designed to investigate the mechanism of cholesterol reduction.
      METHODS: We measured serum levels of cholestanol, a cholesterol absorption
      marker, and lathosterol, a cholesterol synthesis marker, in 20 patients with both
      hypercholesterolaemia and hypertension. Ten patients were treated with
      telmisartan and the remaining 10 with fluvastatin. RESULTS: After 3 months of
      treatment, total and LDL cholesterol levels decreased in the telmisartan group
      (P<0.01 for both total and LDL cholesterol levels) and the fluvastatin group
      (P<0.001 for both total and LDL cholesterol levels). The change in cholestanol
      level after 3 months of treatment was positively correlated with the levels of
      total (R=0.72, P<0.05) and LDL cholesterol (R=0.81, P<0.01) in the telmisartan
      group. The change in lathosterol level was positively correlated with the levels
      of total (R=0.88, P=0.001) and LDL cholesterol (R=0.89, P=0.001) in the
      fluvastatin group. WHAT IS NEW AND CONCLUSIONS: Our results suggest that the
      cholesterol-lowering effect of telmisartan might be caused by inhibition of
      cholesterol absorption, whereas that of statins is by inhibition of cholesterol
      synthesis. If confirmed, co-treatment with the two agents may be useful for
      synergistically lowering cholesterol in hypertensive patients.

PMID- 21198726
TI  - Dabigatran and rivaroxaban for prevention of venous thromboembolism--systematic
      review and adjusted indirect comparison.
AB  - WHAT IS KNOWN AND OBJECTIVE: Dabigatran and rivaroxaban are new oral
      anticoagulants for thromboprophylaxis after elective orthopaedic surgery. We
      aimed to systematically compare their relative benefits and harms through meta
      analysis, and adjusted indirect comparison. METHODS: We searched PubMed, EMBASE,
      trial registries and regulatory documents through May 2009 for randomized
      controlled trials (RCTs) of dabigatran (150 and 220 mg daily) and rivaroxaban (10
      mg daily) compared with enoxaparin (40-60 mg daily) in elective orthopaedic
      surgery. We used random effects meta-analysis to calculate pooled relative risks
      (RRs) and 95% confidence intervals (95% CI) for the outcomes of total venous
      thromboembolism, VTE (deep venous thrombosis, non-fatal pulmonary embolism and
      all-cause mortality), and haemorrhagic adverse events (major and clinically
      relevant non-major bleeds). Adjusted indirect comparison was used for the pooled
      RRs of dabigatran and rivaroxaban with enoxaparin as the common control. RESULTS:
      Rivaroxaban was superior to enoxaparin for the prevention of venous
      thromoboembolism (RR 0.56, 95% CI 0.43-0.73, P<0.0001), with a trend for
      increased haemorrhage (RR 1.26, 95% CI 0.94-1.69, P=0.13). Dabigatran was not
      superior to enoxaparin for prevention of VTE (RR 1.12, 95% 0.97-1.29, P=0.12),
      and did not reduce haemorrhage risk (RR 1.10, 95% 0.90-1.35, P=0.32). Adjusted
      indirect comparison showed that rivaroxaban was superior to dabigatran in
      preventing VTE, RR 0.50 (95% CI 0.37-0.68), but with a slight trend towards
      increased haemorrhage RR 1.14 (95% CI 0.80-1.64). WHAT IS NEW AND CONCLUSION:
      Rivaroxaban may be more effective than dabigatran for prevention of VTE after
      elective orthopaedic surgery but might also slightly increase the risk of
      haemorrhage.

PMID- 21198727
TI  - Celebrating three decades of public policy-oriented interdisciplinary research.

PMID- 21198728
TI  - Electrophoretic techniques: the old and the new.

PMID- 21198730
TI  - Comments on measurement of C-reactive protein in dogs.

PMID- 21198732
TI  - Prevalence of dog erythrocyte antigens in retired racing Greyhounds.
AB  - BACKGROUND: Blood groups in dogs are designated as dog erythrocyte antigen (DEA)
      1.1, 1.2, 3, 4, 5, 7, and Dal. There is limited information about the frequency
      of different antigens in Greyhound dogs, despite their frequent use as blood
      donors. OBJECTIVES: The aims of this study were to determine the frequencies of
      DEA 1.1, 1.2, 3, 4, 5, and 7 in Greyhounds, to compare the frequencies with those
      of non-Greyhound dogs, and to evaluate the presence of naturally occurring anti
      DEA antibodies. METHODS: Blood was collected from 206 Greyhound and 66 non
      Greyhound dogs being screened as potential blood donors. Blood-typing was
      performed at Animal Blood Resources International by tube agglutination utilizing
      polyclonal anti-DEA antibodies. RESULTS: Of the Greyhound dogs, 27/206 (13.1%)
      were positive for DEA 1.1, and this frequency was significantly lower (P<.0001)
      than for non-Greyhound dogs of which 40/66 (60.6%) were DEA 1.1-positive. The
      frequency of positivity for both DEA 1.1 and 1.2 was also lower in Greyhounds
      (P<.0001). There were no significant differences between Greyhounds and non
      Greyhounds for DEA 1.2, 3, 4, 5, or 7. All 137 dogs (113 Greyhounds and 24 non
      Greyhounds) that were evaluated for naturally occurring anti-DEA antibodies in
      serum were negative. A higher percentage of Greyhound dogs (57.3%, 118/206) were
      considered "universal donors" (negative for all DEAs except DEA 4) compared with
      non-Greyhound dogs (28%, 13/46). CONCLUSION: The frequency of positivity for DEA
      1.1 in our population of Greyhounds was significantly lower than previously
      reported for dogs. Furthermore, a large majority of Greyhounds met the criteria
      for universal donors.

PMID- 21198733
TI  - Serum concentrations of IgG, IgA, and IgM in retired racing Greyhound dogs.
AB  - BACKGROUND: Greyhound dogs have significant physiologic, hematologic, and
      biochemical differences when compared with other breeds, including significantly
      lower serum globulin concentration owing to decreases in the alpha- and beta
      globulin fractions. The specific proteins that account for differences in
      globulin concentrations are not known, but IgA and IgM, both beta-globulins, are
      potential candidates. OBJECTIVES: The aims of this study were to measure serum
      IgG, IgA, and IgM in clinically healthy retired racing Greyhounds and compare the
      results with those of age- and sex-matched non-Greyhound dogs. METHODS: Study
      animals included 25 Greyhound and 20 non-Greyhound dogs. Total protein, albumin,
      and total globulin concentrations were determined. IgG, IgA, and IgM
      concentrations were measured using a commercially available radial
      immunodiffusion kit. The Student t-test assuming equal variances was used to
      compare concentrations of immunoglobulins between groups. RESULTS: Serum
      concentrations of IgA and IgM in Greyhounds (IgA=49+/-20 mg/dL; IgM=132+/-47
      mg/dL) were significantly lower than concentrations in non-Greyound dogs
      (IgA=70+/-39 mg/dL; Ig M=212+/-78 mg/dL). Concentrations of IgG did not differ
      between groups. CONCLUSIONS: Mean serum IgA and IgM concentrations in Greyhounds
      were lower than those in non-Greyhound dogs. This may contribute to low serum
      concentrations of beta-globulins in Greyhounds. Specific reference intervals are
      recommended for Greyhounds to avoid possible misdiagnosis of IgA or IgM
      deficiency.

PMID- 21198734
TI  - Comparison of chemistry analytes between 2 portable, commercially available
      analyzers and a conventional laboratory analyzer in reptiles.
AB  - BACKGROUND: Advantages of handheld and small bench-top biochemical analyzers
      include requirements for smaller sample volume and practicality for use in the
      field or in practices, but little has been published on the performance of these
      instruments compared with standard reference methods in analysis of reptilian
      blood. OBJECTIVE: The aim of this study was to compare reptilian blood
      biochemical values obtained using the Abaxis VetScan Classic bench-top analyzer
      and a Heska i-STAT handheld analyzer with values obtained using a Roche Hitachi
      911 chemical analyzer. METHODS: Reptiles, including 14 bearded dragons (Pogona
      vitticeps), 4 blue-tongued skinks (Tiliqua gigas), 8 Burmese star tortoises
      (Geochelone platynota), 10 Indian star tortoises (Geochelone elegans), 5 red
      tailed boas (Boa constrictor), and 5 Northern pine snakes (Pituophis melanoleucus
      melanoleucus), were manually restrained, and a single blood sample was obtained
      and divided for analysis. Results for concentrations of albumin, bile acids,
      calcium, glucose, phosphates, potassium, sodium, total protein, and uric acid and
      activities of aspartate aminotransferase and creatine kinase obtained from the
      VetScan Classic and Hitachi 911 were compared. Results for concentrations of
      chloride, glucose, potassium, and sodium obtained from the i-STAT and Hitachi 911
      were compared. RESULTS: Compared with results from the Hitachi 911, those from
      the VetScan Classic and i-STAT had variable correlations, and constant or
      proportional bias was found for many analytes. Bile acid data could not be
      evaluated because results for 44 of 45 samples fell below the lower linearity
      limit of the VetScan Classic. CONCLUSIONS: Although the 2 portable instruments
      might provide measurements with clinical utility, there were significant
      differences compared with the reference analyzer, and development of analyzer
      specific reference intervals is recommended.

PMID- 21198735
TI  - Exclusion of cytoplasmic fragments in flow cytometric analysis of lymph node
      samples from dogs with lymphoma using membrane-permeable violet laser-excitable
      DNA-binding fluorescent dye (DyeCycle Violet).
AB  - BACKGROUND: Cytoplasmic fragments derived from fragile neoplastic lymphocytes are
      common in samples of lymph nodes collected from dogs with lymphoma. These
      cytoplasmic fragments interfere with accurate gating of target cells and
      quantification protocols used for flow cytometry because of their variable size
      and expression of lymphoid cell surface antigens on their membranes. OBJECTIVE:
      The aim of this study was to develop a method to efficiently exclude cytoplasmic
      fragments from flow cytometric analysis of canine lymph nodes in which lymphoma
      was present. METHODS: Single-cell suspensions of neoplastic cells were prepared
      from biopsy samples and fine-needle aspirates of lymph nodes from 23 dogs with
      lymphoma. Suspensions were stained using a violet laser-excitable (405 nm)
      membrane-permeable DNA-binding fluorescent dye (DyeCycle Violet [DCV]), incubated
      with antibodies against CD3, CD5, CD21, CD22, and CD45, and then stained with 7
      amino-actinomycin D (7-AAD), an argon-excitable (488 nm) membrane-impermeable DNA
      binding fluorescent dye. Multiparameter flow cytometry was used for analysis
      based on selective uptake and laser-activated fluorescence of these dyes.
      RESULTS: Cytoplasmic fragments, which were DCV-negative and CD45-positive, and
      dead cells, which were positive for 7-AAD, were efficiently separated from
      neoplastic cells. CONCLUSION: Staining with DCV is a useful method to improve
      flow cytometric gating methods and quantitative analyses of lymph node samples
      from dogs with lymphoma.

PMID- 21198738
TI  - Predicting thyroxine requirements following total thyroidectomy.
AB  - OBJECTIVE: Optimal thyroxine replacement following total thyroidectomy is
      critical to avoid symptoms of hypothyroidism. The aim of this study was to
      determine the best formula to determine the initiated replacement dose of
      levothyroxine immediately following total thyroidectomy. DESIGN: Prospective
      study. All patients were initiated on 100 MUg levothyroxine and titrated to
      within the reference range for TSH and free T4. Correlations to height, weight,
      age, lean body mass (LBM), body surface area (BSA) and body mass index (BMI) were
      calculated. PATIENTS: One hundred consecutive adult patients underwent total
      thyroidectomy for non-malignant disease. MEASUREMENTS: Comparison between three
      methods of levothyroxine dose prediction, aiming for a levothyroxine dose correct
      to within 25 MUg of actual dose required. RESULTS: Correlations were seen between
      levothyroxine dose and patient age (r=-0.346, P<0.01), bodyweight (r=0.296,
      P<0.01), LBM (r=0.312, P<0.01), BSA (r=0.319, P<0.01) and BMI (r=0.172, P<0.05).
      A regression equation was calculated (predicted levothyroxine dose=[0.943 *
      bodyweight] + [-1.165 * age] + 125.8), simplified to (levothyroxine dose=
      bodyweight - age + 125) pragmatically. Initiating patients empirically on 100 MUg
      post-operatively showed that 40% of patients achieved target within 25 MUg of
      their required dose; this increased to 59% when using a weight-only dose
      calculation (1.6 MUg/kg) and to 72% using the simplified regression equation.
      CONCLUSIONS: A simple calculated regression equation gives a more accurate
      prediction of initiated levothyroxine dose following total thyroidectomy,
      reducing the need for outpatient attendance for dose titration.

PMID- 21198739
TI  - Haplotype effect in the IGF1 promoter accounts for the association between
      microsatellite and serum IGF1 concentration.
AB  - OBJECTIVE: Systemic insulin-like growth factor 1 (IGF1) level is an important
      risk factor for various diseases. The inter-individual variation of serum IGF1 is
      determined by environmental and genetic factors, which are attributed to a
      microsatellite in IGF1 promoter. However, the exact nature of the underlying
      regulatory elements accounting for this association has not been characterized.
      Here, we defined the haplotype patterns, including both SNPs and the
      microsatellite, in the Chinese population, and investigated their regulatory
      effect on serum IGF1 level. This is the first study in which haplotype patterns
      of the microsatellite and SNPs in the IGF1 promoter are examined together.
      METHODS: The linkage disequilibrium (LD) patterns of IGF1 were examined using
      tagSNPs of the IGF1 regulatory region. The microsatellite, three tagSNPs and
      haplotypes were correlated with serum IGF1 concentration in 450 normal
      premenopausal Chinese women. RESULTS: Common alleles of the microsatellite were
      in strong LD with the three tagSNPs and were associated with particular
      haplotypes composed of SNPs. Neither the CA repeat number nor SNPs alone showed a
      robust association with serum IGF1 concentration. On the other hand, the
      haplotype T-19-A-T was significantly associated with serum IGF1 level.
      CONCLUSION: No association was found between SNPs and microsatellite alone.
      However, the haplotype showed better correlation with serum IGF1 level. The
      results indicate that the previously observed correlation with microsatellite was
      because of a haplotype effect in the IGF1 promoter. Microsatellite or tagSNPs
      alone are not the primary regulatory elements of IGF1 expression. The exact
      regulatory genetic variant needs to be defined by functional genetic studies.

PMID- 21198740
TI  - Effects of exercise training on maternal hormonal changes in pregnancy.
AB  - CONTEXT & OBJECTIVE: A recent paper by our group reported that regular aerobic
      exercise during pregnancy led to lower foetal IGF-I and IGF-II concentrations and
      a modest reduction in offspring birth weight when compared with the offspring of
      nontraining control participants. Maternal hormonal alterations in response to
      exercise training may be associated with the regulation of nutrient availability
      for foetal growth through placental regulation of maternal metabolism. OBJECTIVE:
      To determine whether the reduction in offspring size was associated with changes
      in the maternal IGF axis [including placental growth hormone (PGH)], leptin
      and/or free fatty acids (FFA) in response to aerobic exercise training in the
      second half of pregnancy. DESIGN AND SETTING: A randomized, controlled trial of
      exercise in pregnancy. PATIENTS: Eighty-four healthy nulliparous women (mean+/-SD
      age 30+/-4 year, BMI 25.5+/-4 kg/m(2) ). MEASUREMENTS: Serum samples were drawn
      at 19 and 35 weeks gestation to determine serum IGF-I, IGF-II, IGF-binding
      protein-1, IGF-binding protein-3, PGH, leptin and FFA. RESULTS: Exercise training
      in pregnancy had no impact on the pregnancy-related changes in the maternal IGF
      axis. Women in the exercise group experienced a 29% increase in leptin in late
      gestation (P=0.026 vs control) and a trend towards lower FFA (P=0.07 vs control).
      Late pregnancy changes in maternal leptin were inversely related to offspring
      birth weight (r= -0.24, P<0.05) and BMI (r= -0.25, P<0.05). CONCLUSIONS: An
      increase in leptin in exercising pregnant women may reflect subtle changes within
      the placenta in response to regular exercise and may contribute to the reduction
      in offspring size previously reported in this cohort.

PMID- 21198741
TI  - Lean mass and fat mass predict bone mineral density in middle-aged individuals
      with noninsulin-requiring type 2 diabetes mellitus.
AB  - OBJECTIVE: Despite high bone mineral density (BMD), persons with type 2 diabetes
      are at greater risk of fracture. The relationship between body composition and
      BMD in noninsulin-requiring diabetes is unclear. The aim was to examine how fat
      and lean mass independently affect the skeleton in this population. RESEARCH
      DESIGN AND METHODS: Subjects for this cross-sectional analysis were men (n = 78)
      and women (n = 56) aged 40-65 years (56 +/- 6 years) with uncomplicated,
      noninsulin-requiring type 2 diabetes. Total body fat and lean mass, total body,
      hip and lumbar spine BMD were measured with dual energy X-ray absorptiometry.
      Magnetic resonance imaging measured total abdominal, visceral and subcutaneous
      (SQ) fat. RESULTS: Subjects had normal all-site BMD and were obese to overweight
      (body mass index 29-41 kg/m(2)) with controlled diabetes (HbA1c women 6.6 +/-
      1.2%, men 6.7 +/- 1.6%). Lean mass was positively associated with total body,
      hip, femoral neck and hip BMD in both sexes. Fat mass, abdominal total and SQ fat
      were associated with total body and hip BMD in women. In multivariate analyses
      adjusted for sex, lean mass significantly predicted total, hip and femoral neck
      BMD in men and women. In unadjusted models, lean mass continued to predict BMD at
      these sites in men; fat mass also predicted total body, femoral and hip BMD in
      women. CONCLUSIONS: In men and women with uncomplicated, noninsulin-requiring
      diabetes, lean mass significantly predicted BMD at the total body, hip and
      femoral neck. Further research is needed to determine whether acquisition or
      maintenance of lean mass in T2DM can prevent hip fracture in this at-risk
      population.

PMID- 21198742
TI  - How can we meet the information needs of patients with early stage papillary
      thyroid cancer considering radioactive iodine remnant ablation?
AB  - In patients with early stage papillary thyroid carcinoma (PTC) who have had a
      thyroidectomy, the decision must be made to accept or reject radioactive iodine
      remnant ablation (RRA). Counselling patients about this decision can be
      challenging, given the medical evidence uncertainties and the complexity of
      related information. Although physicians are the primary source of medical
      information for patients considering RRA, some patients have a desire for
      supplemental information from sources such as the internet. Yet, thyroid cancer
      resources on the internet are of variable quality, and some may not be applicable
      to the individual case. We have developed a computerized educational tool [called
      a decision aid (DA)], directed to patients with early stage papillary thyroid
      cancer, and intended as an adjunct to physician counselling, to relay evidence
      based medical information on disease prognosis and the choice to accept or reject
      RRA. DAs are tools used to inform patients about available treatment options and
      have been utilized in oncologic decision-making. We tested our web-based DA in
      fifty patients with early stage PTC and found that it improved medical knowledge.
      Furthermore, participants found the technical usability of the tool acceptable.
      We are currently conducting a randomized controlled trial comparing the use of
      the DA plus usual care to usual care alone to confirm the educational benefit of
      the website and examine its impact on the decision-making process. In the future,
      DAs may play an expanded role as an adjunct to physician counselling in the care
      of patients with thyroid cancer.

PMID- 21198744
TI  - The clinical presentation of autoimmune thyroid disease in men is associated with
      IL12B genotype.
AB  - BACKGROUND: Common variants in the interleukin 12B (IL12B) gene are associated
      with predominantly inflammatory (Th1) or antibody-mediated (Th2) immune
      responses. As Hashimoto's disease and Graves' disease are thought to arise from
      mainly Th1 and Th2 immune responses respectively, we hypothesized that IL12B
      genotype may influence the clinical presentation of autoimmune thyroid disease.
      OBJECTIVE: We tested for differences in IL12B genotype between Graves' disease
      and Hashimoto's disease. PATIENTS: We studied a discovery cohort of 203
      Australian women and 37 men with autoimmune thyroid disease, a replication cohort
      of 100 European men and a cohort of 146 Chinese men. INTERVENTION: We analysed
      three IL12B variants: rs41292470, in the promoter; rs3212227, in the 3'
      untranslated region and rs6887695, located 60 kilobases upstream from the coding
      region. RESULTS: In the discovery cohort, rs41292470 and rs3212227 genotypes did
      not differ significantly between Hashimoto's disease and Graves' disease. In
      Australian men (but not women), rs6887695 genotype differed between Hashimoto's
      disease and Graves' disease, with a minor allele frequency (MAF) of 14% and 41%,
      respectively (P=0.034). This result was confirmed in the European men (MAF 24%
      and 41%; P=0.013). On combined analysis of Australian, European and Chinese men
      (N=285), the difference was highly significant (MAF 23% and 45%; P=3*10(-5) ). In
      233 men without thyroid disease, the MAF was 34%, significantly different from
      Graves' disease (P=0.005) and Hashimoto's disease (P=0.029). CONCLUSION: In men
      with autoimmune thyroid disease, a common variant located upstream of the IL12B
      coding region may influence whether patients present with Graves' disease or
      Hashimoto's disease.

PMID- 21198743
TI  - Genetic polymorphisms and obesity influence estradiol decline during the
      menopause.
AB  - OBJECTIVES: Obesity and genetic variation in aromatase and type 1 17-beta
      hydroxysteroid dehydrogenase (HSD) could influence the E2 trajectory of decline
      during the menopause transition. DESIGN AND PARTICIPANTS: E2 trajectories during
      the menopause transition (phenotype) were identified using 5934 data points
      acquired annually from 681 women in Study of Women's Health across the Nation
      (SWAN), a multiethnic study of the mid-life. E2 trajectories were related to
      CYP19 and type I 17-betaHSD single-nucleotide polymorphisms (SNPs) and obesity.
      RESULTS: (log) E2 trajectories began to decline precipitously 2 years before the
      final menstrual period (FMP). The trajectory of the (log) E2 decline varied with
      genotypes and obesity. (log) E2 rates of decline were greater in nonobese women
      than in obese women, P < 0.05. Women with the CYP19rs936306 CT variant had (log)
      E2 rate of decline that was 54% as rapid as the rate of decline of women with the
      TT variant, P < 0.05. (log) E2 rate of decline in women with the CYP19rs749292 GG
      variant was two-thirds the rate of (log) E2 decline in women with the AG variant,
      P < 0.05. (log) Rates of E2 decline with 17-betaHSD SNPs (rs2830, rs592389, and
      rs615942) varied according to genotype within obesity groups. Within each obesity
      group, (log) E2 rate of decline was greater in heterozygous variants and much
      less in homozygotes (P < 0.05). Obese women with selected CYP19 and 17-beta HSD
      gene variants had remarkably different E2 trajectories around the FMP, resulting
      in different postmenopausal E2 levels. The rate of the E2 decline and the
      subsequent postmenopausal E2 levels may be relevant to oestrogen-sensitive
      chronic diseases including cancers.

PMID- 21198745
TI  - Cardiac valve disease and low-dose dopamine agonist therapy: an artefact of
      reporting bias?
AB  - INTRODUCTION: Chronic low-dose cabergoline treatment for microprolactinoma may
      cause cardiac valve pathology, but the evidence is contradictory. We investigated
      whether the expectation of the echocardiographer could influence the report.
      METHODS: Transthoracic echocardiograms from 40 patients aged 49.3 +/- 9.6 (mean
      +/- SD) years (Men:Women 7:33) on long-term cabergoline and bromocriptine therapy
      (duration 9.94 +/- 4.5 years) were randomly assigned to two groups of
      echocardiographers so that each echocardiogram was reported twice. One group was
      told that 'the patients were control subjects' (Group A) and the other that 'the
      patients were on dopamine agonist therapy which is known to cause valve disease'
      (Group B). An observer who was blind to the group scored the reports for
      regurgitation at each valve (scores 0-4; max 16 per case). RESULTS: Mean total
      regurgitation score was significantly higher in Group B (1.43 +/- 1.28; P =
      0.014) than in Group A (0.73 +/- 1.30). The difference was mainly from reporting
      trivial regurgitation: (mitral 16 vs 5, P = 0.005; tricuspid 17 vs 6, P = 0.007
      and pulmonary 8 vs 1, P = 0.013). Mild regurgitation was uncommon (mitral 1 vs 1
      and tricuspid 3 vs 6). Moderate regurgitation occurred in only one case and was
      associated with restriction of the leaflets consistent with the effects of
      cabergoline. Valve thickening was not reported in Group A, but in 9 (23%) mitral
      and 4 (10%) aortic valves in Group B. CONCLUSION: Long-term, low-dose dopamine
      agonist therapy rarely causes cardiac valve disease, but operator bias can lead
      to over-reporting of both valve thickening and trivial regurgitation.

PMID- 21198746
TI  - Thyroid autoimmunity and miscarriage: a meta-analysis.
AB  - OBJECTIVE: To investigate whether thyroid autoimmunity (TAI) is associated with
      increased risk of miscarriage in euthyroid women. METHODS: An electronic search
      was conducted using the databases Medline, PubMed, EMBASE and the Cochrane
      library, from inception to October 2010. A systematic review of the studies on
      the association between TAI and miscarriage was performed. The odd ratios of case
      control studies and relative risks of cohort studies were pooled respectively.
      The software Review Manager (version 4.3.1) was applied for meta-analysis.
      RESULTS: The search strategy identified 53 potentially relevant publications, 22
      of which were included in the meta-analysis. A clear association between thyroid
      autoimmunity and miscarriage was observed with a pooled odds ratio of 2.55 (95%
      CI 1.42-4.57, P=0.002) in eight case-control studies and a pooled relative risk
      of 2.31 (95% CI 1.90-2.82, P<0.000 01) in 14 cohort studies. Women with TAI were
      found to have slightly higher age [age difference, 1.29 years] (95% CI 0.43-2.16,
      P=0.003) and thyroid-stimulating hormone (TSH) levels [TSH difference, 0.61
      mIU/l] (95% CI 0.51-0.71, P<0.000 01) compared with those without TAI.
      CONCLUSION: Based on the currently available evidence, it appears that the
      presence of thyroid autoimmunity is associated with an increased risk of
      spontaneous miscarriage in euthyroid women.

PMID- 21198747
TI  - New insights into mesenchymal stromal cell-mediated T-cell suppression through
      galectins.
AB  - In recent years, a large number of studies have contributed to our understanding
      of the immunosuppressive mechanisms used by mesenchymal stromal cells (MSC).
      These include the expression of indoleamine 2,3-dioxygenase (IDO) and the
      production of soluble immunosuppressive factors, such as, interleukin-10 (IL-10),
      transforming growth factor beta (TGF-beta) and prostaglandin E2 (PGE2). However,
      whether these factors represent the only triggers involved in immunosuppression
      is not clear. Indeed, adding IDO inhibitor or neutralizing antibodies against IL
      10 and TGF-beta to mixed lymphocyte reactions failed to prevent T-cell
      suppression by MSC, suggesting that there is either redundancy in the mechanisms
      of immunosuppression or the involvement of other factors yet to be described.
      Galectins, a family of beta-galactoside binding proteins, now emerge as a main
      regulator of MSC immunosuppressive function. Galectin-1 and galectin-3 are
      constitutively expressed and secreted by human bone marrow MSC. Inhibition of
      galectin-1 and galectin-3 gene expression with small interfering RNAs abrogated
      the suppressive effect of MSC on allogeneic T cells. An increase in our
      understanding of MSC suppressor mechanisms will offer an insight into the use of
      these cells in human therapy such as the treatment of graft-versus-host disease,
      a severe complication after haematopoietic stem cell transplantation.

PMID- 21198748
TI  - Natural cytotoxicity of NC-2+ cells against the growth and metastasis of WEHI-164
      fibrosarcoma.
AB  - We have previously reported a new receptor (NC-2) for natural cytotoxicity (NC)
      on murine leucocytes, identified by monoclonal antibody D9 (mAb D9). Pretreatment
      of mouse spleen cells with different concentrations of mAb D9 in vitro blocked NC
      against WEHI-164, whereas natural killing (NK) activity against YAC-1 was
      unaffected. This paper reports the immune surveillance against the growth of WEHI
      164 tumour cells in mice by NC-2(+) Cells. The kinetics of in vivo reduction in
      NC activity were investigated by treating BALB/c and (CBA * C57BL/6) F1 mice with
      a single injection of 40 MUg of mAb D9 and monitoring splenic NC activity by (51)
      Cr-release assay at intervals from 24 h to 3 weeks. Control mice were injected
      with OKT8 irrelevant antibody. Results showed a significant (P < 0.05) reduction
      in splenic NC activity within 24 h which persisted for up to 1 week. Similar
      results were also obtained when (CBA * C57BL/6) F1 mice were employed (P<0.001).
      In vivo tumour studies were undertaken to investigate the role of NC-2(+) cells
      in surveillance against tumour growth and metastasis of the WEHI-164
      fibrosarcoma. When syngeneic BALB/c mice were injected with 40 MUg of mAb D9 and
      then challenged with 5 * 10(5) WEHI-164 cells, results showed significantly
      increased growth rate of the transplanted WEHI-164 fibrosarcoma and tumour
      nodules in the lungs of animals, when compared to control mice with normal NC
      activity. Our data support an innate surveillance in metastasis and growth of
      WEHI-164 fibrosarcoma in mice.

PMID- 21198749
TI  - Prevention of acute and chronic allograft rejection by combinations of
      tolerogenic dendritic cells.
AB  - It is well known that adoptive transfer of donor-derived tolerogenic dendritic
      cells (DC) helps to reduce acute allograft rejection. However, this method cannot
      effectively prevent grafts from infiltration of inflammatory cells and fibrosis,
      and thus has minimal effect on chronic allograft rejection. In this study, we
      used mitomycin C (MMC) to generate tolerogenic DC and demonstrated that donor
      (Balb/c)-derived MMC-DC could induce hyporesponsiveness of recipient (C57BL/6) T
      cells in vitro, potentially by inducing T-cell apoptosis, decreasing IL-2 and IL
      12 secretion, and increasing regulatory T-cell numbers and IL-10 secretion.
      Furthermore, anti-CD154 monoclonal antibody (mAb) treatment combined with donor
      derived MMC-DC prolonged the survival of the allografts in vivo. The mechanisms
      were similar to those in vitro. Impressively, both acute and chronic rejection
      were prevented when donor and F1 generation (Balb/c * C57BL/6) derived MMC-DC
      were injected together with anti-CD154 mAb into recipients before heart
      allotransplantation. In summary, we showed that donor and F1-derived tolerogenic
      DC have a synergistic effect on induction and maintenance of T-cell regulation
      and the secretion of immunosuppressive cytokines. Moreover, adoptive transfer of
      these two types of DC could inhibit both acute and chronic transplant rejection
      in mice.

PMID- 21198750
TI  - Soluble CD26 / dipeptidyl peptidase IV enhances human lymphocyte proliferation in
      vitro independent of dipeptidyl peptidase enzyme activity and adenosine deaminase
      binding.
AB  - Human CD26 has dipeptidyl peptidase-4 (DPP IV) enzyme activity and binds to
      adenosine deaminase (ADA). CD26 is costimulatory for lymphocytes and has a
      circulating soluble form (sCD26). DPP IV enzyme inhibition is a new successful
      type 2 diabetes therapy. We examined whether the ADA binding and catalytic
      functions of sCD26 contribute to its effects on T-cell proliferation. Wildtype
      soluble recombinant human CD26 (srhCD26), an enzyme inactive mutant (srhCD26E-)
      and an ADA non-binding mutant (srhCD26A-) were co-incubated in in vitro T-cell
      proliferation assays with peripheral blood mononuclear cells (PBMC) stimulated
      with phytohaemagglutinin (PHA), muromonab-CD3 or Herpes simplex virus antigen
      (HSV Ag). Both srhCD26 and srhCD26E- enhanced PHA-induced T-cell proliferation
      dose-dependently in all six subjects tested. srhCD26 and srhCD26A- had no overall
      effect on anti-CD3-stimulated PBMC proliferation in four of five subjects.
      srhCD26, srhCD26E- and srhCD26A- enhanced HSV Ag induced PBMC proliferation in
      low responders to HSV Ag, but had no effect or inhibited proliferation in HSV
      high responders. Thus, effects of soluble human CD26 on human T-cell
      proliferation are mechanistically independent of both the enzyme activity and the
      ADA-binding capability of sCD26.

PMID- 21198751
TI  - Mitogenic response and cytokine production induced by cramoll 1,4 lectin in
      splenocytes of inoculated mice.
AB  - Cramoll 1,4 is a lectin with specific glucose/mannose binding, which is extracted
      from seeds of Cratylia mollis Mart. Many assays have shown the cytokine
      expression activity and anti-inflammatory profile of this lectin. The aim of this
      study was to evaluate the immunostimulatory response, in vitro, of splenocytes in
      mice previously inoculated, in vivo, with C. mollis (Cramoll 1,4) and Canavalia
      ensiformis (Con A) lectins. Results demonstrated higher proliferation indexes
      induced by Cramoll 1,4 than Con A lectin in relation to all experimental groups.
      Cramoll 1,4 and Con A also induced high levels of IL-2, IL-6, IFN-gamma and
      nitric oxide production. Moreover, Cramoll 1,4 did not induce apoptosis and
      stimulated a significant number of cells in the S phase of the cell cycle.
      Results showed that Cramoll 1,4 lectin induces proliferative response and
      suggested that this lectin can be used as a mitogenic agent in immunostimulatory
      assays.

PMID- 21198752
TI  - Mannan-binding lectin (MBL) and MBL-associated serine protease 2 (MASP-2)
      genotypes in colorectal cancer.
AB  - Mannan-binding lectin (MBL) and MBL-associated serine protease 2 (MASP-2) are key
      factors of the lectin pathway of complement activation. Polymorphisms of the MBL2
      and MASP-2 genes affect serum levels of MBL and MASP-2. In patients with
      colorectal cancer (CRC), the MBL and MASP-2 serum levels are increased and high
      MASP-2 levels are associated with recurrence and poor survival, whereas low MBL
      levels predict post-operative pneumonia. It is not known whether these
      associations are genetically based. In this study, the MBL and MASP-2 genotypes
      are investigated in 593 patients with CRC and 348 healthy controls. The potential
      association between genetic profile and infections, recurrence and survival is
      evaluated. Four single-nucleotide polymorphisms (SNPs) of MBL2 were analysed
      using TaqMan assays, with characterization of MBL2 wildtype A, variants B, C and
      D and alleles H/L, Y/X and P/Q. The SNP D120G for MASP-2 was determined. Serum
      levels of MBL and MASP-2 were measured. The MBL2 and MASP-2 genotype distribution
      was similar among patients with CRC and healthy controls and MBL2 genotype
      significantly associated with MBL concentration in serum (P<0.0001). No
      significant association between MBL2/MASP-2 genotype and post-operative
      infectious complications (P=0.33 and 0.22), recurrent cancer or survival (P=0.74
      and P=0.61 respectively) was found. Thus, the increased serum levels of MBL and
      MASP-2 found in patients with CRC are not explained for by genetic profiles. In
      contrast to what has been demonstrated for serum levels of MBL and MASP-2, the
      genotypes do not predict disease course of the CRC patients.

PMID- 21198753
TI  - Production of interleukin-13 is influenced by the interleukin-4 -34TT and -590TT
      genotype in patients with aggressive periodontitis.
AB  - Aggressive periodontitis (AgP) is a specific form of periodontal disease, with
      rapid destruction of the tissues supporting the teeth in otherwise young healthy
      individuals. We recently showed a higher frequency of the interleukin-4 (IL-4) 
      34TT and -590TT genotype in AgP patients compared to controls (P<0.05). Herein,
      we demonstrated that this specific IL-4 genotype exerts its function by
      increasing expression of IL-4 and STAT6, and producing higher concentrations of
      IL-4 in activated CD4+ cells of patients with AgP. In the present study, we
      investigated the effects of the IL-4-specific genotype on IL-13, IL-2 and IFN
      gamma expression and production in activated CD4+ cells of patients with AgP and
      healthy controls. Results revealed higher IFN-gamma and IL-2 expression and
      significantly increased IL-13 production in the cells of the patients who were
      homozygous for the -34T and -590T alleles in comparison with the patients who
      were homozygous for the -34C and -590C alleles (P<0.05). Results of controls with
      the -34C and -590C alleles were similar to those of AgP with the same genotype.
      To our knowledge, the present study is the first to show an effect of the -34TT
      and -590TT genotype on IL-13 production. There is an increased production of IL
      13 by the T cells of aggressive periodontitis patients with the IL-4 genotype.

PMID- 21198754
TI  - Comparison of Th-cell immunity against human bocavirus and parvovirus B19:
      proliferation and cytokine responses are similar in magnitude but more closely
      interrelated with human bocavirus.
AB  - Human parvovirus B19 (B19) has been, for decades, the only parvovirus known to be
      pathogenic in humans. Another pathogenic human parvovirus, human bocavirus
      (HBoV), was recently identified in respiratory samples from children with acute
      lower respiratory tract symptoms. Both B19 and HBoV are transmitted by the
      respiratory route. The vast majority of adults are IgG seropositive for HBoV,
      whereas the HBoV-specific Th-cell immunity has not much been studied. The aim of
      this study was to increase our knowledge on HBoV-specific Th-cell immunity by
      examining HBoV-specific T-cell proliferation, Interferon-gamma (IFN-gamma), IL-10
      and IL-13 responses in 36 asymptomatic adults. Recombinant HBoV VP2 virus-like
      particles (VLP) were used as antigen. HBoV-specific responses were compared with
      those elicited by B19 VP2 VLP. Proliferation, IFN-gamma and IL-10 responses with
      HBoV and B19 antigens among B19-seropositive subjects were statistically similar
      in magnitude, but the cytokine and proliferation responses were much more closely
      correlated in HBoV than in B19. Therefore, at the collective level, B19-specific
      Th-cell immunity appears to be more divergent than the HBoV-specific one.

PMID- 21198755
TI  - NK cells and CD1d-restricted NKT cells respond in different ways with divergent
      kinetics to IL-2 treatment in primary HIV-1 infection.
AB  - Cytokine immunotherapy is being evaluated as adjunct treatment in infectious
      diseases. The effects on innate and adaptive immunity in vivo are insufficiently
      known. Here, we investigate whether combination treatment with antiretroviral
      therapy (ART) and Interleukin-2 (IL-2) of patients with primary HIV-1 infection
      induces sustained increases in circulating NKT cell and NK cell numbers and
      effector functions and investigate how changes are coordinated in the two
      compartments. Patients with primary HIV-1 infection starting ART were analyzed
      for numbers, phenotype and function of NKT cells, NK cells and dendritic cells
      (DC) in peripheral blood before, during and after IL-2 treatment. NKT cells
      expanded during IL-2 treatment as expected from previous studies. However, their
      response to alpha-galactosyl ceramide antigen were retained but not boosted.
      Myeloid DC did not change their numbers or CD1d-expression during treatment. In
      contrast, the NK cell compartment responded with rapid expansion of the CD56(dim)
      effector subset and enhanced IFNgamma production. Expansions of NKT cells and NK
      cells retracted back towards baseline values at 12 months after IL-2 treatment
      ended. In summary, NKT cells and NK cells respond to IL-2 treatment with
      different kinetics. Effects on cellular function are distinct between the cell
      types and the effects appear not to be sustained after IL-2 treatment ends. These
      results improve our understanding of the effects of cytokine immunotherapy on
      innate cellular immunity in early HIV-1 infection.

PMID- 21198756
TI  - TSGA10 - A target for autoantibodies in autoimmune polyendocrine syndrome type 1
      and systemic lupus erythematosus.
AB  - Autoimmune polyendocrine syndrome type 1 (APS1) is a rare monogenic autoimmune
      disorder caused by mutations in the autoimmune regulator (AIRE) gene. High-titre
      autoantibodies are a characteristic feature of APS1 and are often associated with
      particular disease manifestations. Pituitary deficits are reported in
      approximately 7% of APS1 patients, with immunoreactivity to pituitary tissue
      frequently described. Using APS1 patient serum to immunoscreen a pituitary cDNA
      expression library, testis specific, 10 (TSGA10) was isolated. Immunoreactivity
      against TSGA10 was detected in 5/99 (5.05%) patients with APS1, but also in 5/135
      (3.70%) systemic lupus erythematosus (SLE) patients and 1/188 (0.53%) healthy
      controls. TSGA10 autoantibodies were not detected in the serum from patients with
      any other autoimmune disease. Autoantibodies against TSGA10 were detectable from
      a young age in 4/5 positive APS1 patients with autoantibody titres remaining
      relatively constant over time. Furthermore, real-time PCR confirmed TSGA10 mRNA
      to be most abundantly expressed in the testis and also showed moderate and low
      expression levels throughout the entire body. TSGA10 should be considered as an
      autoantigen in a subset of APS1 patients and also in a minority of SLE patients.
      No recognizable clinical phenotype could be found to correlate with positive
      autoantibody reactivity.

PMID- 21198757
TI  - Is a TNF alpha polymorphism responsible for mutations in the TP53 gene?

PMID- 21198758
TI  - Allo-induced acute-phase response; IL-6 identifies a subset of individuals at
      risk for graft injury.

PMID- 21198759
TI  - The aesthetic impact of enamel fluorosis on Irish adolescents.
AB  - OBJECTIVES: To assess the impact of differing degrees of enamel fluorosis on
      dental aesthetics according to Irish adolescents. The same participants also
      aesthetically rated other variations in dental appearances including a carious
      lesion, bleached teeth and a demarcated opacity. METHODS: One hundred and fifty
      adolescents examined seven identical template photographs of an attractive dental
      smile displaying varying levels of enamel fluorosis (TF1, TF2, TF3), a demarcated
      opacity, no fluorosis (TF0), anterior caries and very white or bleached teeth. By
      indicating their level of agreement or disagreement with five statements on a
      five-point Likert scale, the participants rated the aesthetic acceptability of
      each of the photographs. RESULTS: Using paired t-tests with the Bonferroni
      correction, it was found that the photographs depicting the very white teeth and
      anterior caries were rated as the most and least aesthetically pleasing images,
      respectively. There was no significant difference in the ratings of the
      photographs displaying TF0, TF1 and TF2 levels of fluorosis indicating that these
      photographs were viewed similarly (P>0.002). The remaining two photographs (TF3
      and the demarcated opacity) were rated similarly and significantly worse
      (P<0.002) than the photographs showing no or low grades of fluorosis (TF0, TF1
      and TF2). CONCLUSIONS: TF3 level of fluorosis represented the break point at
      which enamel fluorosis became aesthetically objectionable to these participants.
      Low grades of fluorosis (TF1 and TF2) were rated similarly to the photograph
      depicting no fluorosis (TF0).

PMID- 21198760
TI  - Socioeconomic and clinical factors associated with caregivers' perceptions of
      children's oral health in Brazil.
AB  - OBJECTIVES: We assessed how socioeconomic and clinical conditions could affect
      parents' perceptions of their child's oral health. METHODS: A cross-sectional
      study was conducted in a sample of 455 children, aged 1-5 years, representative
      of Santa Maria, a southern city in Brazil. Participants were randomly selected
      among children attending a National Day of Children's Vaccination. Clinical
      examinations provided information on the prevalence of caries, dental trauma, and
      occlusion. The caregivers' perception of children's oral health and socioeconomic
      status were assessed by means of a questionnaire. A Poisson regression model
      using robust variance (Prevalence ratio: PR; 95% CI, P <= 0.05) was performed to
      assess the association between the predictor variables and outcomes. RESULTS:
      Parents were more likely to rate their child's oral health as 'poor' if the
      former earned a lower income and the latter had anterior open bite and dental
      caries. Parents of black children with anterior open bite and dental caries were
      more likely to rate their child's oral health as 'worse than that of other
      children'. CONCLUSIONS: Clinical and socioeconomic characteristics are
      significantly associated with parents' perceptions of their child's oral health.
      Understanding the caregivers' perceptions of children's oral health and the
      factors affecting this could be useful in the planning of public health polices,
      in view of the inequity in the oral health pattern.

PMID- 21198762
TI  - Assessing consistency in oral health-related quality of life (OHRQoL) across
      gender and stability of OHRQoL over time for adolescents using Structural
      Equation Modeling.
AB  - BACKGROUND: The Child Perceptions Questionnaire for children aged 11-14 years
      (CPQ(11-14) ) was developed in Toronto as a measure of the oral health-related
      quality of life (OHRQoL) for children/adolescents. The short form with eight
      items (RSF:8) was also derived. OBJECTIVES: (i) To investigate the consistency of
      RSF:8 in measuring the OHRQoL between boys and girls, (ii) to investigate the
      measurement invariance and stability of RSF:8 in measuring OHRQoL for Hong Kong
      adolescents over time, and (iii) to determine the latent mean differences across
      gender and over time. METHODS: The instrument was administered to 542 adolescents
      aged 12 years and re-administered to the same group of adolescents 3 years later.
      Structural Equation Modeling (SEM) was used to test the measurement invariance at
      different levels. A series of hierarchically nested models (configural structure,
      factor loadings, error variances, factor variances and covariance, intercept
      invariance) were tested by the chi-square difference tests, and the more
      restricted model would be accepted if the chi-square difference test was
      insignificant (P > 0.05). The latent means would be estimated if intercept
      invariance was not accepted. The stability of OHRQoL over time was investigated
      by computing the stability coefficients. RESULTS: For multiple group analysis,
      the model with the level of invariance up to factor variances and covariance was
      accepted (P > 0.05). The latent mean of girls was significantly lower (indicating
      better OHRQoL) than boys in social well-being (SWB). For panel data analysis, the
      model with the level of invariance up to factor variances and covariance was
      accepted (P > 0.05). The latent mean of the four domains decreased significantly
      (indicating improved OHRQoL) for adolescents aged 12-15 years. The stability
      coefficients ranged from 0.14 to 0.73 which demonstrated moderate stability
      except functional limitation (FL) with a relatively low stability. CONCLUSION:
      This study indicated that RSF:8 measured OHRQoL for adolescents in Hong Kong
      consistently across gender. The OHRQoL in SWB for girls was better than boys.
      Also, the OHRQoL for adolescents was in the same factor structure with moderate
      stability and improved significantly over time.

PMID- 21198761
TI  - Language and literacy relate to lack of children's dental sealant use.
AB  - OBJECTIVES: This study aimed to determine the percent of California's third grade
      public school children lacking sealants by child and family factors and to
      measure social disparities for lacking sealants. METHODS: The study analyzed data
      from the California Oral Health Needs Assessment (COHNA) 2004-2005, a complex
      stratified cluster sample of children (n = 10,450) from 182 randomly selected
      public elementary schools in California. The dependent variable was absence of
      sealants in first permanent molars. The independent variables included child
      race/ethnicity; socio-economic position (SEP) measured as child's participation
      in the free or reduced-price lunch program at the individual and school level;
      acculturation measured as language spoken at home and school level percent of
      English language learners; and parent functional health literacy measured as
      correctly following questionnaire instructions. Absolute differences and health
      disparity indices (i.e. Slope Index of Inequality, Relative Index of Inequality
      mean, Absolute Concentration Index) were used to measure absolute and relative
      disparities. RESULTS: The percent of children lacking sealants was high in all
      racial/ethnic groups; no child or school level SEP differences in lacking
      sealants were seen, but significant differences existed by acculturation (child
      and school level) and parental functional health literacy. CONCLUSIONS:
      NonEnglish language and poor parental functional health literacy are potential
      barriers that need to be addressed to overcome disparities in sealant
      utilization.

PMID- 21198763
TI  - Oral health-related quality of life of 11- and 12-year-old public school children
      in Rio de Janeiro.
AB  - OBJECTIVES: The objective of this study was to assess the association between
      oral health-related quality of life (OHRQoL), measured through the Child-OIDP,
      and demographic characteristics, self-reported oral problems, and clinical oral
      health measures, among 11- to 12-year-old school children in the city of Rio de
      Janeiro, Brazil. METHODS: A cross-sectional study was conducted, having as its
      target population 11- and 12-year-old students of both sexes, formally enrolled
      in 6- and 7-year school classes at public schools. A probabilistic sample with
      complex design was used. OHRQoL was assessed by the Brazilian version of Child
      OIDP. Oral exams were conducted, and the presence of dental biofilm, gingival
      bleeding, DMFT, fluorosis, enamel defects, dental trauma, and malocclusion were
      recorded. RESULTS: A total of 571 school children participated with a mean age of
      12.0 years and 95% confidence interval (95% CI) from 11.9 to 12.1. A total of
      88.7% of the school children presented the impact of oral problems in at least
      one of the eight daily performances. The activities that had most impacts were
      eating (81.3%), cleaning mouth (40.5%), and smiling (32.2%). The mean Child-OIDP
      index was 7.1 with 95% CI from 6.2 to 8.1. The highest scores were in relation to
      eating (mean = 25.0; 95% CI from 22.4 to 27.6), cleaning mouth (mean = 12.0; 95%
      CI from 9.1 to 14.9), and smiling (mean = 10.0; 95% CI from 7.5 to 12.5). In the
      logistic regression model, the Child-OIDP was associated with dental caries
      experience and with the perception of sensitive teeth, perception of gingival
      bleeding, and perception of inadequate position of the teeth. In the multinomial
      regression, we found that the odds of having higher levels of Child-OIDP were
      positively associated with dental caries experience. Self-reported dental caries,
      mobile milk teeth, tooth position, bleeding gums, and bad breath were associated
      with worst OHRQoL. CONCLUSIONS: It can be concluded that there is an association
      between dental caries experience and the Child-OIDP index. This association
      indicates the impact of this condition on the quality of life of school children.
      Moreover, the Child-OIDP index is explained more by self-reported oral problems
      than by clinical normative measures.

PMID- 21198764
TI  - Angiogenic activity of an enamel matrix derivative (EMD) and EMD-derived
      proteins: an experimental study in mice.
AB  - OBJECTIVES: To determine whether all or only certain proteins in an enamel matrix
      derivative (EMD) are angiogenic. MATERIALS AND METHODS: The angiogenic effect was
      analysed using an in vivo angiogenesis assay. Silicon tubes were filled with or
      without potential and known angiogenic-modulating factors: (i) an EMD parent,
      (ii) nine pools of EMD proteins, (iii) fibroblast growth factor/vascular
      endothelial growth factor and (iv) amelogenin. Silicon tubes were implanted
      subcutaneously in mice. Dextran-fluorescein isothiocyanate (FITC) was injected
      via the tail vein, mice were euthanized and tubes were retrieved.
      Neovascularization was determined by measuring the amount of dextran-FITC within
      the tubes. RESULTS: The greatest angiogenic potential of the EMD parent was at a
      weight of 125 ng, resulting in a 4.3-fold increase compared with the negative
      control. Five pools of EMD proteins showed a stronger angiogenic activity than
      the EMD parent. Pool 5 showed the greatest angiogenic activity, when compared
      with the negative control (8.1-fold increase) and with 125 ng of the EMD parent
      (4.2-fold increase). Amelogenin demonstrated a significantly higher angiogenic
      activity than the negative control (increase up to 4.0-fold) and the EMD parent
      (increase up to 1.6-fold). CONCLUSIONS: EMD parent, recombinant porcine
      amelogenin and certain pools of EMD proteins induced significant angiogenesis
      compared with the controls using a standardized in vivo assay.

PMID- 21198765
TI  - Association between periodontal infection and obesity: results of the Health 2000
      Survey.
AB  - AIM: To investigate the role of periodontal infection in obesity in an adult
      population. MATERIAL AND METHODS: This study was based on a subpopulation of the
      Health 2000 Survey that included dentate, non-diabetic subjects, aged 30-49 years
      (n=2784). Obesity was measured using the body mass index (BMI), body fat
      percentage (BF%) and waist circumference (WC). The extent of periodontal
      infection was measured using the number of teeth with deepened (4 mm deep or
      deeper) periodontal pockets and was categorized into four categories (0, 1-3, 4
      6, 7 or more). RESULTS: The number of teeth with deepened periodontal pockets was
      found to be associated with BMI in an exposure-response manner among the total
      study population. The association was found among men and women, and also among
      never-smokers. The number of teeth with deepened periodontal pockets was also
      associated with BF% and WC among never-smokers. CONCLUSION: Periodontal infection
      measured by means of the number of teeth with deepened periodontal pockets
      appears to be associated with obesity. However, no inferences about causality can
      be made and further studies are needed to clarify the possible role of
      periodontal infection in obesity.

PMID- 21198767
TI  - BsmI, TaqI, ApaI, and FokI polymorphisms in the vitamin D receptor gene and
      periodontitis: a meta-analysis of 15 studies including 1338 cases and 1302
      controls.
AB  - AIM: A meta-analysis was conducted in order to investigate the potential
      association of vitamin D receptor (VDR) gene polymorphisms with susceptibility to
      aggressive and chronic periodontal disease. MATERIAL AND METHODS: A database
      search yielded a total of 15 studies involving 1338 cases and 1302 controls. Four
      polymorphisms were included in the meta-analysis: VDR TaqI (rs731236), VDR BsmI
      (rs1544410), VDR FokI (rs2228570), and VDR ApaI (rs7975232). Odds ratios (ORs)
      along with their 95% confidence intervals (CIs) were computed to compare the
      distribution of alleles and genotypes between cases and controls. RESULTS AND
      CONCLUSIONS: The combined results based on all studies showed that (1) chronic
      periodontitis cases had a significantly lower frequency of bb genotype of BsmI
      [OR=0.63, 95% CI=0.42, 0.94; p=0.02] in Asians; (2) chronic periodontitis cases
      had a significantly higher frequency of AA genotype of ApaI (OR=2.20, 95%
      CI=1.39, 3.48; p<0.001) in Asians; (3) chronic periodontitis cases had a weak
      significantly higher frequency of TT genotype of TaqI (OR=1.86, 95% CI=1.002,
      3.46; p=0.049) in Asians. After Bonferroni's correction, we found that in Asians
      chronic periodontitis cases still had a significantly higher frequency of AA
      genotype of ApaI. No significant difference was found in any genotype of FokI. No
      association was found for all the VDR gene polymorphisms examined as far as the
      aggressive form of the disease is concerned. Future studies need to focus on the
      possible biological consequences and mechanisms of the VDR genetic variants. The
      current findings confirm that VDR gene is a candidate gene for periodontitis.

PMID- 21198768
TI  - Socio-economic position, smoking, and plaque: a pathway to severe chronic
      periodontitis.
AB  - AIM: To report periodontal status and elucidate the relationship among socio
      economic position (SEP), plaque accumulation, tobacco smoking, and periodontitis
      in a representative sample of adult Jewish people, aged 35-44 years, living in
      Jerusalem. METHODS: This cross-sectional study was conducted using a stratified
      sample of two hundred and fifty-four 35-44-year-old adults in Jerusalem (limited
      to the Jewish population). A clinical examination (Community Periodontal Index
      and Plaque Index) and a self-administered questionnaire were applied. RESULTS:
      Two hundred and fifty-four adults, mean age 38.6 (SD=3.3) years, participated.
      The response rate was 88%; intra-examiner kappa values were above 0.87. The
      average number of healthy sextants was 1.18, while the average number of sextants
      with bleeding, calculus, shallow periodontal pockets, and deep periodontal
      pockets was 1.3, 2.6, 0.7, and 0.1, respectively. Lower level of education was
      associated with severe chronic periodontitis (SCP, p=0.012) and also with smoking
      (p=0.030) and higher level of plaque (p<0.001). Smoking was associated with
      higher level of plaque (p<0.001), which in turn was associated with SCP
      (p=0.020). CONCLUSION: This study presented a potential explanatory pathway for
      the relationship between SEP and SCP. Low level of education was proposed as a
      distal determinant, leading to tobacco smoking and higher levels of plaque, and
      finally to SCP.

PMID- 21198766
TI  - Influence of smoking on gingival crevicular fluid cytokines in severe chronic
      periodontitis.
AB  - AIM: The aim of this study was to compare the expression of 22 chemokines and
      cytokines in gingival crevicular fluid (GCF) from smokers and non-smokers with
      periodontitis and periodontally healthy control subjects. MATERIALS AND METHODS:
      Forty subjects with generalized severe chronic periodontitis (20 smokers and 20
      non-smokers) and 12 periodontally healthy control subjects participated in this
      study. Four diseased and two healthy sites were selected from each of the
      periodontitis subjects. GCF samples were collected and cytokines analysed
      utilizing a multiplexed immunoassay (Luminex((r)) ). Statistical analyses
      employed non-parametric tests including the Mann-Whitney and Wilcoxon matched
      pairs signed-rank tests. RESULTS: Compared with healthy control subjects, GCF in
      subjects with chronic periodontitis contained significantly higher amounts of
      interleukin (IL)-1alpha, IL-1beta, IL-6, IL-12(p40) (pro-inflammatory cytokines);
      IL-8, macrophage chemotactic protein (MCP)-1, macrophage inflammatory protein
      (MIP)-1alpha, regulated on activation normal T-cell expressed and secreted
      (RANTES) (chemokines); IL-2, IFN-gamma, IL-3, IL-4 (Th1/Th2 cytokines); IL-15
      [regulator of T-cells and natural killer (NK) cells]. Smokers displayed decreased
      amounts of pro-inflammatory cytokines [IL-1alpha, IL-6, IL-12(p40)], chemokines
      (IL-8, MCP-1, MIP-1, RANTES), and regulators of T-cells and NK cells (IL-7, IL
      15). CONCLUSIONS: Periodontitis subjects had significantly elevated cytokine and
      chemokine profiles. Smokers exhibited a decrease in several pro-inflammatory
      cytokines and chemokines and certain regulators of T-cells and NK-cells. This
      reflects the immunosuppressant effects of smoking which may contribute to an
      enhanced susceptibility to periodontitis.

PMID- 21198772
TI  - Modulation of exteroceptive suppression periods in human jaw-closing muscles by
      subanaesthetic dose of propofol.
AB  - Exteroceptive suppression (ES) periods in human jaw-closing muscles can be
      conditioned by a wide range of somatosensory stimuli and cognitive states. The
      aim of this study was to examine the effects of subanaesthetic doses of
      midazolam, ketamine and propofol on the short latency (ES1) and long latency
      (ES2) reflex in the jaw-closing muscles. First, we tried to evaluate the various
      methodological criteria for ES recording. We then examined the effect of
      subanaesthetic doses of midazolam (0.035 mg kg(-1)), ketamine (0.30 mg kg(-1))
      and propofol (0.35 mg kg(-1)) on these reflexes of recording left masseter and
      temporalis muscle. ES duration did not differ greatly in the present study,
      recorded with the correct adjustment of stimulating and recording conditions.
      None of the subanaesthetic doses of the agents influenced ES1, and no significant
      effects on ES2 were observed with midazolam and ketamine. However, significant
      inhibitory change was observed in ES2 with propofol. ES2 is thought to be
      mediated by afferents, which descend in the spinal trigeminal tract and connect
      with a polysynaptic chain of excitatory interneurones located in the lateral
      reticular formation. Our observations indicate that propofol is uniquely
      effective not only through involvement of the gamma-aminobutyric acid type A
      receptor, but also through a range of other effects.

PMID- 21198773
TI  - Five-year clinical evaluation of In-Ceram crowns fabricated using GN-I (CAD/CAM)
      system.
AB  - This study prospectively evaluated the clinical performance of computer-assisted
      design and computer-assisted manufacturing (CAD/CAM)-generated In-Ceram Alumina
      core crowns in Japanese patients for up to 5 years. A total of 101 In-Ceram
      crowns with aluminium copings fabricated using the GN-I system were placed in
      Japanese patients. The crowns were evaluated using a California Dental
      Association (CDA) quality assessment system at baseline and at all follow-up
      examinations. Gingival condition was assessed using plaque and bleeding scores.
      The survival of anterior and posterior crowns was analysed according to the
      Kaplan-Meier method. The scores of gingival condition were compared between
      restored crowns and contralateral teeth using a t-test. During the observation
      period, six crowns were lost to follow-up. Five crowns were fractured from the
      copings and removed, and four crowns were removed for other reasons. Chipping
      within the porcelain was detected in three crowns, which were then polished. The
      cumulative survival rates after 60 months were 96.9% for anterior crowns and
      87.7% for posterior ones, and there were no significant differences between
      anterior and posterior crowns. According to the CDA criteria, most of the crowns
      were rated as satisfactory during the observation period. There were significant
      differences in soft tissue conditions between In-Ceram crowns and control teeth
      at 2- and 5-year examinations. Despite the five fractures from copings, In-Ceram
      Alumina crowns with copings fabricated using the CAD/CAM (GN-I system) for
      replacing both anterior and posterior teeth showed predictable results during a 5
      year observation period.

PMID- 21198774
TI  - Edentulism, use of dentures and consumption of fruit and vegetables in south
      Brazilian community-dwelling elderly.
AB  - There is evidence suggesting that edentulous older persons modify their diet,
      avoiding foods that are difficult to chew, such as fruit and vegetables;
      meanwhile, the consumption of these foods is associated with prevention of
      chronic diseases. However, few studies evaluated whether a poor oral status
      without prosthetic rehabilitation is associated with a reduction in the
      consumption of fruit and vegetables in community-dwelling older persons. We
      evaluated the association of oral status with emphasis on complete dentures use
      with the daily consumption of at least 400 g of fruit and vegetables, following
      the recommendations of the WHO. A random sample of 282 south Brazilians >=60
      years of age was evaluated. Measurements included a questionnaire to assess
      sociodemographic, behaviour, and health data; consume of fruit and vegetables by
      means of a 24-h diet recall, and oral status assessment, by means of oral
      examinations assessing the number of teeth and use of dental prosthesis.
      Multivariate Poisson regression showed that the only variable significantly
      associated with inadequate consumption of fruit and vegetables was edentulism
      with the use of only one denture [PR=1.75 (1.11-2.74)]. Edentulous participants
      wearing only one denture were less likely to consume at least 400 g day(-1) of
      fruit and vegetables. These results indicate that, in edentulous community
      dwelling elderly, oral health rehabilitation might play an important role in the
      maintenance of consumption of adequate amounts of fruit and vegetables, which is
      an important component of a healthy diet and also in the prevention of chronic
      diseases.

PMID- 21198776
TI  - Peer relationships and suicide ideation and attempts among Chinese adolescents.
AB  - BACKGROUND: Suicide is a global health concern. Therefore, studying suicide
      behaviour and identifying the early roots of suicide are critical. To address
      these issues, the present study examined (i) the association between peer
      relationships and suicide ideation and attempts among Chinese adolescents; and
      (ii) whether such associations were moderated or mediated by feeling of
      loneliness. We hypothesized that problems in peer relationships were positively
      associated with suicide ideation and attempts, and that feeling of loneliness
      would moderate and mediate such associations. METHODS: The sample included 8778
      Chinese adolescents from a large survey. Measures of peer relationships, suicide
      ideation and attempts, and feeling of loneliness were obtained through
      adolescents' self-reports. RESULTS: Results from multivariate logistic
      regressions suggested that specific problems in peer relationships, such as lack
      of peer association and being victimized by bullying, were significantly related
      to suicide ideation and attempts. In addition, the moderating effects of feeling
      of loneliness on the association between peer relationships and suicide ideation
      and attempts were found. Finally, some gender effects were also found.
      CONCLUSIONS: The present study provided strong evidence that suicide ideation and
      attempts were serious problems among adolescents in China, to which peer
      relationships played an important role. Further, feeling of loneliness acted as a
      moderator affecting the association between peer relationships and suicide
      ideation and attempts. Finally, there were some gender differences that have
      important implications.

PMID- 21198775
TI  - Weight loss induced by 6-month lifestyle intervention improves early endothelial
      activation and fibrinolysis in obese adolescents.
AB  - BACKGROUND: Adolescent obesity is associated with an increased risk of adult
      obesity and subsequent cardiovascular diseases. The present study aimed to assess
      the effect of weight loss after 6-month lifestyle intervention in obese
      adolescents on biomarkers of endothelial activation and fibrinolytic system.
      METHODS: Eighty-five obese adolescents aged 10 to 16 years were assigned to a 6
      month lifestyle intervention and 61 completed the programme. We examined the
      effect of the intervention on adhesion molecules (selectin E, soluble
      intercellular adhesion molecule 1 and soluble vascular adhesion molecule 1) and
      fibrinolytic parameters [plasminogen activator inhibitor-1 (PAI-1) and
      fibrinogen]. Thirty-six lean adolescents were studied only at baseline as a
      comparison group. RESULTS: Compared with lean participants, obese adolescents at
      baseline demonstrated significantly higher levels of triglycerides, glucose,
      insulin, homeostasis model assessment, soluble intercellular adhesion molecule 1,
      PAI-1 and fibrinogen. After 6-month lifestyle intervention, those obese
      adolescents with decreased standard deviation score-body mass index (SDS-BMI)
      displayed significant decreases in insulin (19.2 +/- 11.2 vs. 26.8 +/- 13.2 mU/L,
      P<= 0.01), homeostasis model assessment (4.24 +/- 3.19 vs. 6.58 +/- 4.08, P<=
      0.01), selectin E (100.2 +/- 60.9 vs. 116.0 +/- 69.0 ng/mL, P<= 0.01) and PAI-1
      (39.6 +/- 38.0 vs. 51.8 +/- 25.6 ng/mL, P<= 0.05) with respect to the baseline
      levels. No changes in these parameters were observed in the obese adolescents
      with stable or increased SDS-BMI. The changes of triglycerides after intervention
      in subgroup with decreased SDS-BMI were significantly greater than those in
      subgroup with stable SDS-BMI. CONCLUSIONS: The present study demonstrated
      increased endothelial activation and impairment of the fibrinolytic system in
      early life, which is in part reversible by a 6-month lifestyle intervention.

PMID- 21198777
TI  - Child and parental surveys about pre-hospitalization information provision.
AB  - BACKGROUND: There is little available information about what children and parents
      would like to know about a forthcoming hospitalization and what they currently
      receive. METHODS: The current study was a survey of 102 children between the ages
      of 6 and 10 years and their parents recruited either from the Recovery Unit
      following day surgery or from the wards following overnight admissions at Sydney
      Children's Hospital, Australia. Information was obtained about each child's
      experience in hospital, the nature and format of information that they had
      received prior to the admission, and what information the child/parent thought
      would be helpful to receive. RESULTS: Parents recorded a total of 163 questions
      asked by children prior to their admission. Questions related to timing (e.g.
      duration of admission, length of procedure), pain, procedural information,
      anaesthesia, needles, whether parents can be present, activities to do in
      hospital, seeking explanations ('Why' questions), hospital environment, seeking
      reassurance and miscellaneous questions. Children who were satisfied with the
      amount of information they received before coming to hospital subsequently
      reported that they would be significantly less scared should they need to come
      back to hospital for a future procedure. A total of 46.7% of children received
      information about their hospitalization from their parent(s) and a further 12%
      from a doctor and parent. CONCLUSIONS: Children were found to have many questions
      about a forthcoming hospitalization. Parents were found to have a major role as
      information providers. Further research is needed to assess parental confidence
      and competence to meet their child's information needs.

PMID- 21198778
TI  - Parents evaluation of the processes of care in child rehabilitation: a
      reliability study of the Norwegian translation of MPOC-20.
AB  - BACKGROUND: The objective was to assess the reliability of the Norwegian
      translation of the Canadian Measure of Processes of Care-20 (MPOC-20)
      questionnaire for use in child rehabilitation in Norway. MPOC-20 is a
      standardized questionnaire with 20 items and 5 scales that assesses to what
      extent parents experience that the services offered to them and their children
      are in line with the ideologies and principles of the family-centred service
      (FCS). METHODS: The translation of MPOC-20 was performed according to
      international standards for translation of questionnaires. A pilot study was
      carried out with representatives from four patient advocacy organizations. A test
      retest reliability study was performed. MPOC-20 (N) was sent to the participants
      twice with 2- to 6-week intervals. Participants were 36 parents of 25 children
      aged 0-18 years. Response rate was 41.8%. RESULTS: The intraclass correlations
      (ICCs) for test-retest scores ranged 0.78-0.86. The internal consistency
      expressed as Cronbach's alpha ranged 0.62-0.93; the score was high for four of
      the scales and acceptable for the fifth 'Providing specific information'. These
      findings strongly suggest that the five scales of MPOC-20 (N) have good test
      retest reliability. Average scores of each scale did not differ significantly
      between the first and second rating, indicating that the average scores of the
      ratings are stable. CONCLUSIONS: The Measure of Processes of Care-20 (N) appears
      to be reliable and useful in the Norwegian context, and can be recommended for
      evaluation of the processes of child rehabilitation(1) in Norway.

PMID- 21198780
TI  - Severity of coronary atherosclerosis is an independent predictor of the left
      ventricular ejection fraction.
AB  - 1. We studied the association between the level of the left ventricular ejection
      fraction and the severity of coronary atherosclerosis. 2. The study population
      consisted of 850 consecutive patients who underwent coronary angiography for
      suspected or known coronary atherosclerosis. Anthropometric measurements
      including the body mass index, blood pressure, blood lipids, blood glucose and
      leucocyte count were taken. The severity of coronary atherosclerosis was defined
      by the Gensini score. 3. When the level of the left ventricular ejection fraction
      was examined as a categorical variable classified by quartile values, subjects
      with a high left ventricular ejection fraction level had significantly lower
      Gensini scores than those with a low left ventricular ejection fraction level
      (P=0.000). Spearman's correlation analysis suggested that the left ventricular
      ejection fraction was significantly negatively associated with Gensini score (r= 
      0.213, P=0.000). Multiple stepwise linear regression analysis showed that the
      Gensini score was significantly independently associated with the left
      ventricular ejection fraction level (beta= -0.194, P=0.000). Furthermore,
      multivariable stepwise logistic regression analysis showed that the Gensini score
      was the independent risk factor for dysfunction of left ventricular ejection
      (OR=2.048, 95% CI=1.517-2.763). 4. The severity of coronary atherosclerosis was
      defined by the Gensini score. This was a strong and statistically highly
      significant predictor of the left ventricular ejection fraction level and
      dysfunction of left ventricular ejection independent of other major risk factors
      including age, body mass index, blood pressure, fasting blood glucose, blood
      lipid and leucocyte count.

PMID- 21198781
TI  - Frontiers in Research Review: Stress and Hypertension. Introduction.

PMID- 21198784
TI  - Abstracts of the 2010 Annual Meeting of the German Clinical Pharmacologists.
      November 4-6, 2010. Wuerzburg, Germany.

PMID- 21198785
TI  - Linear basal cell carcinoma occurs most commonly on the lower eyelid.

PMID- 21198786
TI  - Depression, anxiety and health-related quality of life in children and
      adolescents with vitiligo.
AB  - BACKGROUND: Only a limited number of studies have studied the relationship
      between vitiligo and psychiatric morbidity and quality of life (QOL) in children
      and adolescents. AIM: To determine levels of depression, anxiety and QOL in
      children and adolescents with vitiligo. METHODS: In total, 41 outpatients with
      vitiligo aged 8-18 years and a control group were assessed using the Child
      Depression Inventory (CDI), State-Trait Anxiety Inventories for Children (STAI-C)
      and Pediatric Quality of Life Inventory, Parent and Child versions (PedsQL-P and
      PedsQL-C). Both study and control groups were divided into child (8-12 years old)
      and adolescent (13-18 years old) groups to exclude the effect of puberty on
      psychological condition. RESULTS: Children with vitiligo scored higher on the CDI
      compared with controls; no other significant differences were found between the
      groups. Vitiligo severity correlated negatively with psychosocial score on PedsQL
      P in the adolescent group. Duration of the illness was positively related to
      physical health score on PedsQL-P in the child group. Involvement of the face,
      head or neck in boys and involvement of the genital area and legs in girls were
      related to impaired QOL. CONCLUSIONS: Vitiligo relates to the severity of
      depression in children, but a similar effect was not observed in adolescents. We
      suggest that the location of the lesions is a significant factor that leads to
      QOL impairment, possibly because of its effects on identity development.

PMID- 21198787
TI  - Examination of AKAP12 promoter methylation in skin cancer using methylation
      sensitive high-resolution melting analysis.
AB  - BACKGROUND: A kinase anchor protein 12 (AKAP12/gravin) belongs to a family of
      scaffold proteins and organizes protein kinase (PK)A and PKC. DNA
      hypermethylation in the AKAP12 promoter region has been reported in a variety of
      human cancers with the exception of skin cancer. Methylation-specific high
      resolution melting (MS-HRM) analysis is a novel tool for analysis of promoter
      methylation. AIM: To use MS-HRM analysis to detect the methylation levels of the
      AKAP12 gene in skin samples. METHODS: In total, 195 samples, including basal cell
      carcinoma, squamous cell carcinoma and actinic keratosis were examined. MS-HRM
      analysis was used to detect methylation levels of the AKAP12 gene in these
      samples. RESULTS: MS-HRM analysis successfully detected the methylation of AKAP12
      in skin samples. The frequencies of AKAP12 methylation in all three types of skin
      abnormalities were significantly higher than in normal tissues. CONCLUSIONS:
      Application of MS-HRM analysis proved to be a fast and high-throughput method to
      investigate the epigenetic status of AKAP12. Methylation of AKAP12 can be
      detected in different skin abnormalities.

PMID- 21198788
TI  - Epidermal photoprotection: comparative study of narrowband ultraviolet B minimal
      erythema doses with and without stratum corneum stripping in normal and vitiligo
      skin.
AB  - BACKGROUND: Recent accumulating data in the literature have indicated a complex
      photoprotective role of the epidermis, and the role of melanin as the major
      epidermal photoprotective mechanism has become debatable. AIM: Comparative
      assessment of the photoprotective roles played by different epidermal structures
      and compounds. METHODS: In total, 64 participants, comprising patients with
      vitiligo (n = 32) and healthy volunteers (n = 32), with skin phototypes (SPTs) II
      to V, were enrolled in the study. Areas of skin were delineated; for both
      lesional and nonlesional skin, the stratum corneum (the SC) was stripped,
      followed 24 h later by exposure to narrowband ultraviolet B (NB-UVB) irradiation,
      to measure the minimal erythema dose (MED) in normal, stripped normal,
      vitiliginous and stripped vitiliginous skin models. These MED values were used to
      assess the photoprotective role of epidermal structures: melanin, viable
      epidermis (VE) and the SC. RESULTS: In the vitiligo group, the MED values were
      significantly (P < 0.05) different between the skin models, being highest in
      normal skin, followed by stripped normal, vitiliginous and stripped vitiliginous
      skin. A similar significance level was found within each SPT for almost all
      comparisons. There was also a significant (P < 0.001) positive correlation
      between MED and SPTs. There were also significant (P < 0.05) differences in MED
      values calculated for epidermal structures, being highest for VE, followed by
      melanin and then the SC, and there was a significant (P < 0.05) positive
      correlation between MED and SPTs. CONCLUSION: Epidermal photoprotection may
      extend beyond melanin production, involving several factors such as epidermal
      layer thickness, optical properties and chromophores. Such a role was perceived
      to be reactive to UV irradiation, and more efficient in those with higher SPTs.

PMID- 21198789
TI  - A study of ApaI and TaqI genotypes of the vitamin D receptor in Egyptian patients
      with psoriasis.
AB  - BACKGROUND: Vitamin D analogues have been found to be effective in treating the
      skin lesions of psoriasis. The therapy is thought to work through the vitamin D
      receptors, resulting in alteration of the proliferation/differentiation balance
      of the cells. Vitamin D also has an effect on T helper cells, which have a major
      role in the pathogenesis of psoriasis. There is controversy about the association
      of vitamin D receptor gene polymorphisms with psoriasis in different populations,
      and it is a factor that might influence the treatment of these patients. AIM: To
      study vitamin D receptor gene polymorphisms using two restriction enzymes in a
      group of Egyptian patients with psoriasis. METHODS: In total, 50 patients with
      psoriasis were examined using restriction fragment length polymorphism analysis
      to study ApaI and TaqI genotypes of the vitamin D receptor in a sample of
      Egyptian patients, and compared with 50 healthy control subjects. RESULTS: We did
      not find any significant difference in ApaI and TaqI vitamin D receptor gene
      polymorphisms between patients and controls. CONCLUSIONS: There is ethnic
      variability in vitamin D receptor gene polymorphisms. The lack of significant
      prevalence of the studied gene polymorphisms in our population suggests that
      their association with other functionally known gene polymorphism might have a
      role in the pathogenesis of psoriasis.

PMID- 21198790
TI  - Therapeutic efficacy of mizoribine for discoid lupus erythematosus with
      normalized frequency of circulating T helper 17 cells.

PMID- 21198791
TI  - Role of interleukin-17 in the pathogenesis of vitiligo.
AB  - BACKGROUND: Skewing of the immune response towards T helper (Th)1 or Th17 and
      away from regulatory T cells (Tregs) and Th2 cells may be responsible for the
      development and progression of autoimmune disease. An autoimmune theory has been
      proposed in the pathogenesis of vitiligo. No previous reports have investigated
      alterations in IL-17 produced by Th17 cells in lesional skin in vitiligo. AIM: To
      investigate the role of IL-17 in the pathogenesis of vitiligo by assessing its
      levels in lesional skin and serum of patients with vitiligo compared with
      controls. METHODS: In total, 30 patients with vitiligo and 20 controls matched
      for age and gender were enrolled in the study. Serum and tissue IL-17 levels were
      measured by ELISA and compared between both groups for correlations with age,
      gender, family history, disease duration, activity of vitiligo and percentage of
      involved body surface area. RESULTS: A significant difference between patients
      and healthy controls was found for both serum and tissue IL-17 levels (P<0.001
      for both). Significant positive correlations were found between disease duration
      and IL-17 level in both serum (r=0.42, P=0.02) and lesional skin (r=0.45,
      P<0.015); between extent of vitiligo and IL-17 levels in both serum (r=0.65,
      P<0.001) and skin (r=0.48, P<0.05); and between the serum and the tissue IL-17
      levels in patients with vitiligo (r=0.54, P=0.002). CONCLUSIONS: Multiple factors
      have been implicated in the pathogenesis of vitiligo. The increased levels of IL
      17 we found in serum and lesional skin suggest an important role for this
      cytokine in the pathogenesis of vitiligo.

PMID- 21198792
TI  - Preservation of eyebrows during laser tattoo removal.

PMID- 21198793
TI  - Evidence for the absence of mutations at GJB3, GJB4 and LOR in progressive
      symmetrical erythrokeratodermia.
AB  - BACKGROUND: Progressive symmetrical erythrokeratodermia (PSEK) is a rare
      inherited cornification disorder characterized by symmetrical erythematous
      hyperkeratotic plaques. The genetic basis for PSEK is not clear. PSEK shares many
      clinical features with erythrokeratodermia variabilis (EKV), which is associated
      with mutations in genes coding for gap junction beta (GJB) 3 and 4. A mutation in
      the loricrin gene (LOR) was found in patients with PSEK, who were members of a
      family with Vohwinkel syndrome. It would therefore be of interest to determine if
      PSEK is also caused by mutations in these genes. AIM: To examine the mutation
      status of GJB3, GJB4 and LOR in patients with PSEK and in control subjects.
      METHODS: Genomic DNA samples from 25 patients with PSEK and 56 healthy controls
      were examined by sequencing analysis of the coding sequences of GJB3, GJB4 and
      LOR. RESULTS: There were no mutations found in any of these three genes.
      CONCLUSIONS: PSEK is a disorder distinct from EKV, and the true pathogenesis of
      PSEK remains unknown.

PMID- 21198794
TI  - Unusual presentation of onychomycosis caused by Exophiala (Wangiella)
      dermatitidis.

PMID- 21198795
TI  - Local complications of erysipelas: a study of associated risk factors.
AB  - BACKGROUND: Local complications of erysipelas include haemorrhagic, bullous,
      abscessing and necrotic lesions. The risk factors predisposing patients to local
      complications are not fully known. AIM: To examine local complications of
      erysipelas and to identify possible risk factors predisposing to their
      appearance. METHODS: Medical records from all patients hospitalized with
      complications of erysipelas (purpura, bullae, abscesses and necrosis), admitted
      to the University Hospital of Heraklion between 1994 and 2002, were
      retrospectively studied. Clinical and laboratory data were compared with those
      from patients with erysipelas without local complications. RESULTS: In total, 145
      patients were analysed, of whom 46 had local disease complications. Using
      bivariate analysis, the factors significantly associated with disease
      complications were found to be age >= 51 years, obesity, longer duration of local
      symptoms, and fever on admission. During hospitalization, increased C-reactive
      protein level, isolation of pathogens, longer duration of fever and/or presence
      of leucocytosis, absence of response to initial antibiotic therapy, and longer
      length of hospitalization were also associated with complications in the
      bivariate analysis. However, in the multivariate analysis, obesity (OR 4.489, 95%
      CI 1.719-11.725, P = 0.002) was the only independent factor associated with
      complicated erysipelas. CONCLUSIONS: This study found obesity to be an
      independent risk factor for local complications, of erysipelas. Hence, obese
      patients with erysipelas are prone to complications, and should be carefully
      evaluated because of the potential severity of disease and the increased risk of
      failure of empirical antimicrobial therapy.

PMID- 21198796
TI  - Immunofluorescence of the outer root sheath: an aid to diagnosis in pemphigus.
AB  - BACKGROUND: The direct immunofluorescence (DIF) pattern of the outer root sheath
      (ORS) of the hair follicle in patients with pemphigus resembles that of
      perilesional skin. We performed DIF on anagen and telogen hair ORS from patients
      with pemphigus and compared the findings with those of perilesional skin. AIM: To
      assess the sensitivity of DIF in the ORS of anagen and telogen hair in patients
      with pemphigus with positive DIF results in perilesional skin. METHODS: In total,
      50 patients with active pemphigus and positive DIF findings in perilesional skin
      were selected for the study. Anagen hair was obtained from the scalp by the same
      method used for a trichogram, and telogen hair was selected by combing the hair
      and collecting the loose strands of hair from the comb. The hair type was further
      confirmed by microscopy. Hair samples were transported in Michel medium and
      prepared for DIF by mounting on a slide without sectioning. Anagen and telogen
      hair samples were also collected from 50 controls. RESULTS: Immunological
      deposits characteristic of pemphigus were found in the ORS of anagen and telogen
      hairs in all 50 patients, but in none of the 50 controls. Positive DIF findings
      were seen in scalp hair irrespective of the presence of scalp lesions. Of the 50
      patients with pemphigus, 46 were diagnosed with pemphigus vulgaris, 2 with
      pemphigus vegetans, and 1 each with pemphigus foliaceus and pemphigus
      erythematosus, based on the clinical, histopathological and DIF findings. All the
      pemphigus variants had positive DIF findings in the ORS. CONCLUSIONS: Using DIF
      on telogen hair ORS promises to be a useful tool for diagnosis and follow-up in
      cases of pemphigus.

PMID- 21198797
TI  - A Japanese-specific recurrent mutation and a novel splice site mutation in the
      LAMC2 gene identified in two Japanese families with Herlitz junctional
      epidermolysis bullosa.
AB  - BACKGROUND: Herlitz junctional epidermolysis bullosa (H-JEB) is an extremely rare
      genodermatosis characterized by lethality owing to severe blister formation. We
      report two unrelated Japanese patients with H-JEB. Genetic analyses detected a
      single nonsense mutation on the LAMC2 gene in these two patients. AIM: To
      identify the mutation involved and describe the first reported Japanese recurrent
      mutation in the LAMC2 gene. METHODS: Direct sequencing was performed of DNA from
      either peripheral blood or fetal cells in amniotic fluid. Reverse transcriptase
      PCR was used to confirm that an aberrant transcript resulted from the splice site
      mutation. A haplotype analysis was performed to define the origin of the
      recurrent mutation. RESULTS: Both patients had blisters and erosions on the trunk
      and limbs at birth, with nail dystrophy. Patient 1 died as a result of sepsis at
      30 weeks of age, and patient 2 died as a result of disseminated intravascular
      coagulation at 20 weeks of age. Mutation analysis of the LAMC2 gene revealed that
      patient 1 was compound heterozygous for a nonsense mutation (p.Cys553X) and a
      novel splice site mutation (c.2868+1delG), and patient 2 was a homozygous for
      p.Cys553X. Prenatal diagnosis performed during a subsequent pregnancy in family 2
      revealed that this second child was heterozygous for p.Cys553X, and was thus not
      affected. Haplotype analysis suggested that a p.Cys553X allele derived from the
      same origin had been independently inherited by these two unrelated families.
      CONCLUSIONS: p.Cys553X in the LAMC2 gene may be a Japanese-specific recurrent
      mutation as a result of a founder effect, and it may therefore be useful for
      initial screening in the mutation analysis of H-JEB.

PMID- 21198798
TI  - Effects of p-coumaric acid on erythema and pigmentation of human skin exposed to
      ultraviolet radiation.
AB  - BACKGROUND: It has been recently recognized that p-coumaric acid (PCA) is a
      strong inhibitor of cellular melanogenesis. AIM: To evaluate the erythema
      suppressive and skin-lightening effects of PCA after topical application to human
      skin. METHODS: The control and PCA cream products were applied twice daily to the
      skin of the forearm of 21 subjects before and after ultraviolet (UV) irradiation
      to determine whether they could prevent erythema formation and pigmentation. The
      cream products were also applied to different areas only after the induction of
      erythema or pigmentation to determine whether they could have a depigmenting
      effect. RESULTS: A 7-day application of control and PCA cream products before UV
      irradiation decreased UV-induced erythema formation by 31% and 77%, respectively,
      compared with untreated skin. When the PCA cream was applied after UV
      irradiation, its effects on skin colour or pigmentation were less remarkable.
      However, the melanin index was significantly decreased at the sites treated with
      PCA cream for 70 days compared with control sites, and the Individual Typology
      Angle (ITA degrees ) value was increased significantly. Of the 21 subjects, 2 had
      mild adverse skin reactions to both the PCA and control creams. CONCLUSION: These
      results suggest that PCA cream can reduce UV-induced erythema formation and
      subsequent pigmentation in human skin.

PMID- 21198799
TI  - Abstracts of the XXVIIIth International Congress of the International Academy of
      Pathology. October 10-15, 2010. Sao Paulo, Brazil.

PMID- 21198801
TI  - Effect on pain of changing the needle prior to administering medicine
      intramuscularly: a randomized controlled trial.
AB  - AIM: This paper is the report of a study to determine whether changing the needle
      before administering an intramuscular injection could reduce pain, and to
      investigate gender differences in pain perception. BACKGROUND: A skilled
      injection technique can make the patient's experience less painful and avoid
      unnecessary complications, and the use of separate needles to draw up and
      administer medication ensures that the tip of the needle is sharp and free from
      medication residue. METHOD: A randomized controlled trial was carried out between
      January 2009 and May 2009 with 100 patients receiving diclofenac sodium
      intramuscularly in an emergency and traffic hospital in Izmir, Turkey. The
      primary outcome was pain intensity measured on a numerical rating scale. Each
      patient received two injections by the same investigator using two different
      techniques. The two techniques were randomly allocated and the patients were
      blinded to the injection technique being administered. After each injection,
      another investigator who had no prior knowledge of which injection technique was
      used immediately assessed pain intensity using a numerical rating scale.
      Descriptive statistics, paired t-test and t-test were used to evaluate the data.
      RESULTS: Findings demonstrated that changing the needle prior to intramuscular
      medication administration significantly reduced pain intensity. A statistical
      difference in pain intensity was observed between the two injection techniques.
      CONCLUSION: The results supported the hypothesis that changing the needle prior
      to administering the medicine significantly reduced pain intensity.

PMID- 21198800
TI  - Computer- and web-based interventions to increase preadolescent and adolescent
      physical activity: a systematic review.
AB  - AIM: This review examined evidence regarding computer- or web-based interventions
      to increase preadolescent and adolescent physical activity. BACKGROUND: Today's
      youth are less active and more overweight than their counterparts from 25 years
      ago. Overweight youth tend to become overweight adults with weight-related
      maladies, including type 2 diabetes and cardiovascular problems. Interventions to
      increase physical activity that reach a large audience are needed. Computer- and
      web-based physical activity interventions are an appealing means to influence
      physical activity in preadolescents and adolescents. However, their effectiveness
      must be determined. DATA SOURCES: The following electronic databases were
      searched for studies published from 1998 through 2010: CINAHL, PubMed, PsycINFO,
      Sociological Abstracts, SportDISCUS and Proquest. REVIEW METHODS: A systemic
      review was conducted. Fourteen randomized control trials or quasi-experimental
      studies were reviewed to: (1) determine the effect of computer- or web-based
      interventions on increasing physical activity and/or improving body mass index,
      weight, percent body fat or waist circumference as a result of increasing
      physical activity; and (2) examine if additional components associated with these
      interventions increased success. RESULTS:   Although most interventions
      demonstrated statistically significant increases in physical activity or positive
      health changes related to physical activity, findings were small or short-lived.
      The value of conducting the interventions at school, using a theory or model as a
      framework, and supplementing with individual tailoring and parental involvement,
      is discussed. CONCLUSION: Computer- and web-based interventions can promote
      physical activity among preadolescents and adolescents, particularly in schools.
      However, further efforts are needed to sustain positive changes.

PMID- 21198802
TI  - Deficient knowledge of multidrug-resistant bacteria and preventive hygiene
      measures among primary healthcare personnel.
AB  - AIM: This paper is a report of a study conducted to describe primary healthcare
      personnel's knowledge of multidrug-resistant and preventive hygiene measures.
      BACKGROUND: The group of patients at risk for multi-drug resistant bacteria is
      largely cared for in primary care. Knowledge of multidrug-resistant and hygiene
      preventive measures among primary healthcare personnel is therefore essential.
      METHOD: A descriptive and comparative questionnaire survey among primary
      healthcare personnel was performed in 2008. In total, five urban and rural
      primary healthcare centres situated in one county in central Sweden were
      included. Convenient sampling was used and 10 physicians, 38 district nurses and
      10 nursing assistants participated. Knowledge/medical facts concerning multidrug
      resistant and hygiene preventive measures were investigated and data were
      analysed using a quantitative approach. RESULTS: Knowledge/medical facts
      concerning several aspects of multidrug-resistant bacteria, particularly Extended
      Spectrum-Beta-Lactamase producing bacteria, were deficient as was knowledge of
      different aspects of hygiene preventive measures. Physicians showed significantly
      better results than district nurses and nursing assistants did. Awareness of
      proper hand-washing as an effective preventive method and use of aprons in
      nursing care was high among all participants. Staff who knew they had cared for
      these patients had significantly better results than the others did. CONCLUSION:
      Our findings suggest that evidence-based education of multidrug-resistant and
      hygiene preventive measures, in primary health with subsequent follow-ups should
      become a prioritized clinician and management concern. Research is needed that
      focus implementation of evidence-based educations, staff attitudes and
      responsibilities related to the work with patients at risk of multidrug-resistant
      bacteria.

PMID- 21198803
TI  - Randomized controlled trial of a dementia care programme for families of home
      resided older people with dementia.
AB  - AIM: This paper reports a study to examine the effectiveness of a 6-month
      dementia care programme for Chinese families living with and caring for a
      relative with dementia, compared with routine family support services in Hong
      Kong. BACKGROUND: Recognizing the adverse psychosocial health effects inherent in
      dementia care, different psychosocial interventions provided preliminary evidence
      of their effectiveness in improving family members' knowledge and skills in
      caregiving and delaying dementia sufferers' illness deterioration and
      institutionalization. Little is known about the effects of such interventions for
      family caregivers' psychosocial health conditions, particularly in non-Western
      populations. METHODS: A randomized controlled trial was conducted with 92 Chinese
      families of a relative with dementia in two dementia care centres in Hong Kong.
      They were randomly selected from a dementia client list and then randomly
      assigned to receive either the dementia family care programme (n=46), or routine
      care only (n=46). Clients' symptoms and institutionalization, and caregivers'
      quality of life, burden and social support at recruitment, 1 week, and 12 and 18
      months following intervention were measured and compared between the study groups
      using repeated measures MANOVAS followed by Helmert's contrast tests. Data was
      collected over a period of 24 months, between September 2007 and August 2009.
      RESULTS: Results of the MANOVAS and contrast tests indicated that at 18-month
      follow-up, participants in the family programme reported significantly greater
      improvements in clients' symptoms and institutionalization rates, and caregivers'
      quality of life and burden, when compared with their counterparts in the routine
      care group. CONCLUSION: These findings provide evidence that the dementia care
      family programme can improve the psychosocial functioning of both clients with
      dementia and their family caregivers in a Chinese population. Further research is
      recommended to investigate whether this intervention can also apply to families
      with different socio-economic backgrounds and across cultures.

PMID- 21198804
TI  - Data-based nurse staffing indicators with Bayesian networks explain nurse job
      satisfaction: a pilot study.
AB  - AIM: This paper is a report of a pilot study to examine the relationship of
      nursing intensity, work environment intensity and nursing resources to nurse job
      satisfaction. BACKGROUND: There is an ever increasing amount of information in
      hospital information systems; however, still very little of it is actually used
      in nursing management and leadership. METHODS: The combination of a retrospective
      time series and cross-sectional survey data was used. The time series patient
      data of 9704 in/outpatients and nurse data of 110 nurses were collected from six
      inpatient units in a medical clinic of a university hospital in Finland in 2006.
      A unit-level measure of nurse job satisfaction was collected with a survey (n =
      98 nurses) in the autumn of 2006. Bayesian networks were applied to examine a
      model that explains nurse job satisfaction. RESULTS: In a hospital data system,
      18 usable nurse staffing indicators were identified. There were four nurse
      staffing indicators: patient acuity from nursing intensity subgroup, diagnosis
      related group volume from work environment subgroup, and skill mix and nurse
      turnover from nursing resources subgroup that explained the likelihood of nurse
      job satisfaction in the final model. The Bayesian networks also revealed the
      elusive non-linear relationship between nurse job satisfaction and patient
      acuity. CONCLUSION: Survey-based information on nurse job satisfaction can be
      modelled with data-based nurse staffing indicators. Nurse researchers could use
      the Bayesian approach to obtain information about the effects of nurse staffing
      on nursing outcomes.

PMID- 21198805
TI  - Systematic development and validation of a nursing intervention: the case of
      lifestyle adherence promotion in patients with leg ulcers.
AB  - AIMS: To describe and discuss of the added value of systematic development and
      validation of nursing interventions in nursing care. BACKGROUND: An adherence
      promoting intervention for leg ulcer patients was developed in 2008, based on the
      model of van Meijel. This model requires a systematic development using an
      analysis of patients' (lived) experiences and professionals' views on (good)
      care. It employs a cyclical process of trying out, evaluating, revising and
      reassessing the adapted intervention in patients. The intervention consists of
      information and counselling sessions carried out by tissue viability nurses and
      focuses on wearing compression hosiery, practising leg elevation, physical
      activity and performing leg exercises. DISCUSSION: Exploring patients' and
      nurses' perspectives during the development of intervention increases the
      likelihood that the resultant intervention is both feasible and attuned to
      patients' needs. Various implementation issues were identified during the
      developmental process. Validation of the intervention through its use in nursing
      care aids in refining the intervention and in linking the techniques most
      successful in effecting behavioural change to theoretical constructs. It
      contributes to the refinement of concepts of behavioural theories by clarifying
      the processes underlying the intervention's effectiveness. Direct involvement of
      the researcher in the validation phase has great added value. IMPLICATIONS FOR
      NURSING: Patient involvement in intervention development is essential, as is the
      researcher's direct involvement in practical situations in which the intervention
      is tested. Qualitative (evaluation) approaches are recommended. CONCLUSION:
      Although the systematic development of nursing interventions is time-consuming,
      the contribution to the development of nursing practice and nursing science makes
      it worthwhile.

PMID- 21198806
TI  - Patients' experience of living with glaucoma: a phenomenological study.
AB  - AIM: To explore the life experiences of those living with glaucoma and describe
      their strategies to deal with the consequences of this disorder. BACKGROUND:
      Glaucoma, the second most common cause of worldwide blindness, often imposes
      limitations on the daily functions of its victims, thus resulting in a decline in
      their quality of life and high costs in healthcare. METHODS: A hermeneutical
      phenomenological research approach was adopted. Fourteen people with glaucoma
      were selected for in-depth interviews, and another ten were interviewed in two
      focus groups. Participants were recruited from a specialized eye hospital in
      Shanghai. The data were collected from July to September 2009. An interpretive
      analysis of the data was performed. FINDINGS: The core theme was identified while
      interpreting the data on the patients' life experiences as 'learning to living
      with glaucoma' by one of our participants. The meaning of this is demonstrated in
      four interwoven themes: (1) seeking support; (2) coping with everyday tasks; (3)
      living with future uncertainties; and (4) adapting to the declined quality of
      life. CONCLUSION: This paper provides an insight into the living experiences of
      the patients with glaucoma using 1-on-1 and focus-group interviews, suggesting
      that the latter can also offer a means of phenomenological inquiry. We found that
      those with glaucoma can experience uncertainty surrounding treatment, illness
      prognosis and family members' risk status. In addition, the Chinese culture can
      influence the patients' strategies of maintaining a healthy lifestyle. In helping
      those with glaucoma considerations should be taken towards the feelings of future
      uncertainty that may develop.

PMID- 21198807
TI  - Predictors of self-efficacy and self-rated health for older male inmates.
AB  - AIMS: The aims of this study were to examine: (1) the relationships between self
      efficacy for health management and (a) health-promoting behaviours, (b) health
      monitoring behaviours, and (c) self-rated health status in older male prisoners;
      and (2) the variations in self-rated health status and self-efficacy for health
      management by inmate characteristics of older men in prison. BACKGROUND: The
      greying of the inmate population around the globe can be attributed to increases
      in punitive crime control practices, life expectancy; and the ageing baby boom
      generation. Older inmates are typically not a healthy group. Therefore, the needs
      of burgeoning numbers of older, sicker inmates are issues of international
      significance. METHODS: A descriptive, correlational, survey was conducted from
      late 2007 to mid-2008 with Bandura's self-efficacy model as the guiding
      framework. RESULTS/FINDINGS: Participants were 131 male inmates, aged 50 and
      older. A statistically significant positive relationship was found between self
      efficacy for health management and the indexes measuring health-promoting
      behaviours (r=0.550; P<0.001), health-monitoring behaviours (r=0.323; P=0.001),
      and the single item rating for self-rated health (tau(b)=0.411; P<0.001). There
      was a tendency for education to be positively related to self-rated health but
      not self-efficacy (tau(b)=0.140; P=0.054 and tau(b)=0.105; P=0.122,
      respectively). Years of incarceration was not significantly related to self-rated
      health or self-efficacy. CONCLUSION: These research findings support Bandura's
      self-efficacy theoretical work and its applicability to health-related research
      in prisons. Nurses are front line healthcare providers in prison, who are in a
      key position to implement interventions that promote greater inmate self-efficacy
      for healthy behaviours and chronic disease management.

PMID- 21198808
TI  - Public health nursing initiates publication of Cochrane nursing care field review
      summaries.

PMID- 21198809
TI  - Landlord attitudes and behaviors regarding smoke-free policies: implications for
      voluntary policy change.
AB  - OBJECTIVE: The study purpose was to describe multiunit landlord attitudes and
      behaviors toward smoke-free policies. DESIGN AND SAMPLE: This was a descriptive,
      cross-sectional survey of multiunit landlords in Douglas County (N=392).
      MEASURES: A 25-item survey was developed and pilot tested. It was administered by
      telephone (n=143) and mail (n=249) to multiunit landlords. RESULTS: Combined
      response rate was 30.1% (81/143 telephone, 37/249 mail) representing 24,080 units
      on 974 properties with 34,399 tenants. Most respondents (73.7%) allowed smoking.
      Reasons for not implementing smoke-free policies were potential enforcement
      problems (57.0%), tenant objections (43.0%), loss of market share (39.5%).
      Respondents without smoke-free policies expected vacancy (53.6%) and turnover
      (50.0%) rates to increase, which was significantly different (p <.0001) than
      respondents with smoke-free policies where only 10.7% reported increased vacancy
      and only 3.7% reported increased turnover. CONCLUSIONS: Expected adverse impacts
      of smoke-free policies do not reflect real experiences of smoke-free policy
      implementation. Public health advocates can use these study findings to develop
      community-based education and social marketing messages directed at voluntary
      smoke-free policy changes. Respondents without smoke-free policies expressed
      interest at the end of the survey in learning how to implement smoke-free
      policies indicating a readiness for change.

PMID- 21198810
TI  - Barriers to mask wearing for influenza-like illnesses among urban Hispanic
      households.
AB  - OBJECTIVES: To identify barriers to mask wearing and to examine the factors
      associated with the willingness to wear masks among households. DESIGN AND
      SAMPLE: We used data sources from a study assessing the impact of 3
      nonpharmaceutical interventions on the rates of influenza: exit interviews; home
      visits with a subset of the mask group; and a focus group. MEASURES: Risk
      perception score, univariate analysis, and logistic regression were conducted to
      identify the characteristics and predictors of mask use. Thematic barriers to
      mask wearing were identified from qualitative data obtained at home visits and
      focus group. RESULTS: Respondents from the mask group, when compared with the
      nonmask group, demonstrated higher risk perception scores concerning influenza
      (maximum score: 60, means: 37.6 and 30.2, p<.001) and increased perception of
      effectiveness of mask wearing (maximum score: 10, means: 7.8 and 7.3, p=.043).
      There was no significant association between demographic, attitudinal, or
      knowledge variables and adherence to wearing masks. Thematic barriers were
      identified such as social acceptability of mask use, comfort and fit, and
      perception of the risk/need for masks. CONCLUSIONS: Face masks may not be an
      effective intervention for seasonal or pandemic influenza unless the risk
      perception of influenza is high. Dissemination of culturally appropriate mask use
      information by health authorities and providers must be emphasized when educating
      the public.

PMID- 21198811
TI  - Three population-patient care outcome indicators for public health nursing:
      results of a consensus project.
AB  - OBJECTIVES: Difficulties in recruiting nurses into public health settings
      threaten the public's health. Gaps in existing data make determining the health
      impact of workforce changes numbers difficult to perform. Public health practice
      leaders are left to make difficult staffing and program decisions without knowing
      how the health of their vulnerable populations will be affected. The objective of
      this study was to identify indicators that could be used to document the effect
      of the shortage of public health nurses (PHNs) on the health of a population.
      DESIGN AND SAMPLE: A consensus-building process was used. Nursing directors from
      6 local health departments (LHDs) in 2 states participated along with 3 public
      health system researchers. RESULTS: The findings from this collaborative process
      suggest that it is possible to identify outcome indicators across states and
      multiple LHDs that may be sensitive to PHN staffing levels and interventions.
      Possible connections between PHN staffing and each population-patient care
      indicator (rates of Chlamydia, first trimester prenatal care, early childhood
      immunization) are presented. CONCLUSIONS: The process used here in identifying
      these indicators and the proposed nursing-sensitive population outcome indicators
      themselves provide a template for the development and analysis of additional
      outcome indicators sensitive to the quality of nursing and other health care.

PMID- 21198812
TI  - Barriers and facilitators in the delivery of environmental risk reduction by
      public health nurses in the home setting.
AB  - OBJECTIVE: The goal of this study was to identify the factors that contributed to
      or detracted from the ability of public health nurses (PHNs) to deliver
      environmental risk reduction (ERR) in the home setting. DESIGN AND SAMPLE:
      Structured one-to-one interviews were conducted with 10 PHNs from 2 county health
      departments in the western United States that were delivering an ERR intervention
      in a randomized clinical trial. RESULTS: Barriers to incorporating ERR into PHN
      practice were: a change in the perceived mission of public health, nurses' lack
      of environmental health (EH) training, the absence of a strong relationship with
      EH, the multidimensional role of PHNs, presentation of nurse participation by
      management, incorporation of ERR visits into nursing schedules, and challenges
      engaging parents in EH. Facilitating factors included: training and support,
      opportunities for capacity building, belief that ERR is important, building a
      more visible face for PHN, and personal interest in EH and ERR. CONCLUSIONS:
      Adapting PHN practice to include ERR strategies is feasible, but not without
      challenges. With adequate training, time, and institutional support, multiple
      challenges can be overcome. PHNs are well positioned to improve the health of
      families and communities by integrating ERR into their scope of practice.

PMID- 21198813
TI  - Motivation to quit smoking among relatives of lung cancer patients.
AB  - OBJECTIVE: The purpose of this study was to determine the factors related to
      motivation to quit among smoking family members of lung cancer patients. DESIGN
      AND SAMPLE: Relatives of multidisciplinary lung cancer clinic patients were
      recruited during family members' treatment. Participants (N=29) were primarily
      female and Caucasian. MEASURES: The items assessed included the effect of their
      relative's disease on motivation to quit, intent to quit in the next 6 months,
      stage of change, perceived risk from smoking, and attitudes about being
      approached about cessation. RESULTS: Most indicated that their relative's disease
      had increased motivation to quit smoking (71%); 72% planned to quit within 6
      months. One fourth (28%) were in precontemplation stage of change; 65% in
      contemplation; and 7% in preparation. The average perceived risk of developing
      lung cancer was 6.3. Two thirds were glad or very glad that someone had talked
      with them about quitting; 91% thought it was somewhat or very appropriate to talk
      about cessation with family members of lung cancer patients. Motivation to quit
      smoking was positively correlated with stage of change and perceived lung cancer
      risk. CONCLUSIONS: Public health nurses who interact with families of lung cancer
      patients may be able to promote cessation in an at-risk group that is motivated
      to quit smoking.

PMID- 21198814
TI  - The 'WHO Safe Communities' model for the prevention of injury in whole
      populations: a review summary.

PMID- 21198815
TI  - Reduction versus abrupt cessation in smokers who want to quit: a review summary.

PMID- 21198816
TI  - Creating a brand image for public health nursing.
AB  - Public health nurses (PHNs) have declined as a proportion of both the nursing and
      the public health workforces in the past 2 decades. This decline comes as 30
      states report public health nursing as the sector most affected in the overall
      public health shortage. Taken together, these data point to a need for renewed
      recruitment efforts. However, the current public images of nurses are primarily
      those of professionals employed in hospital settings. Therefore, this paper
      describes the development of a marketable image aimed at increasing the
      visibility and public awareness of PHNs and their work. Such a brand image was
      seen as a precursor to increasing applications for PHN positions. A multimethod
      qualitative sequential approach guided the branding endeavor. From the thoughts
      of public health nursing students, faculty, and practitioners came artists'
      renditions of four award-winning posters. These posters portray public health
      nursing-incorporating its image, location of practice, and levels of protection
      afforded the community. Since their initial unveiling, these posters have been
      distributed by request throughout the United States and Canada. The overwhelming
      response serves to underline the previous void of current professional images of
      public health nursing and the need for brand images to aid with recruitment.

PMID- 21198817
TI  - The ethics of sin taxes.
AB  - ABSTRACT The current global economic crisis is forcing governments to consider a
      variety of methods to generate funds for infrastructure. In the United States,
      smoking-related illness and an obesity epidemic are forcing public health
      institutions to consider a variety of methods to influence health behaviors of
      entire target groups. In this paper, the author uses a public health nursing
      model, the Public Health Code of Ethics (Public Health Leadership Society, 2002),
      the American Nurses' Association (ANA) Code of Ethics (2001), and other relevant
      ethical theory to weigh and balance the arguments for and against the use of sin
      taxes. A position advocating the limited use of sin taxes is supported as a
      reasonable stance for the public health professional.

PMID- 21198819
TI  - Conceptual model for partnership and sustainability in global health.
AB  - Although nursing has a long history of service to the global community, the
      profession lacks a theoretical and empirical base for nurses to frame their
      global practice. A study using grounded theory methodology to investigate
      partnership and sustainability for global health led to the development of a
      conceptual model. Interviews were conducted with 13 global health nurse experts.
      Themes from the interviews were: components for engagement, mutual goal setting,
      cultural bridging, collaboration, capacity building, leadership, partnership,
      ownership, and sustainability. Next, the identified themes were reviewed in the
      literature in order to evaluate their conceptual relationships. Finally, careful
      comparison of the interview transcripts and the supporting literature led to the
      Conceptual Framework for Partnership and Sustainability in Global Health Nursing.
      The model posits that engagement and partnership must precede any planning and
      intervention in order to create sustainable interventions. This conceptual
      framework will offer nurses important guidance for global health nursing
      practice.

PMID- 21198818
TI  - The Henry street consortium population-based competencies for educating public
      health nursing students.
AB  - The Henry Street Consortium, a collaboration of nurse educators from universities
      and colleges and public health nurses (PHNs) from government, school, and
      community agencies, developed 11 population-based competencies for educating
      nursing students and the novice PHN. Although many organizations have developed
      competency lists for experts, the Consortium developed a set of competencies that
      clearly define expectations for the beginning PHN. The competencies are utilized
      by both education and practice. They guide nurse educators and PHNs in the
      creation of learning experiences that develop population-based knowledge and
      skills for baccalaureate nursing students. Public health nursing leaders use the
      competencies to frame their expectations and orientations for nurses who are new
      to public health nursing. This paper explains the meaning of each of the 11
      population-based competencies and provides examples of student projects that
      demonstrate competency development. Strategies are suggested for nurse educators
      and PHNs to promote effective population-based student projects in public health
      agencies.

PMID- 21198820
TI  - Go down to suffering and raise it up.
AB  - In a partial reprint of a January 1919 editorial from The Public Health Nurse,
      readers will find an Editor's attempt to find meaning in the long, bitter, and
      highly destructive Great War, known in contemporarily as World War I. The Editor
      expresses hope that something constructive can emerge from so much devastation.
      Parallels to contemporary conflicts are readily apparent. Veterans, specifically
      nurses returning from the battlefields of Europe in this excerpt, deserve
      acknowledgement and through the knowledge of suffering gained in war, use the
      skills they possess to advance health and human happiness in times of peace.

PMID- 21198821
TI  - Assessment of aortic stiffness in marfan syndrome using two-dimensional and
      Doppler echocardiography.
AB  - BACKGROUND: Extracellular matrix remodeling in the aortic wall results in
      increased aortic stiffness (AoS) in Marfan syndrome (MFS). Pulsed-wave velocity
      (PWV) constitutes the best indirect AoS measurement. We aimed to assess PWV in
      MFS patients using two-dimensional (2D) and Doppler echocardiography. METHODS:
      Thirty-one MFS patients, (mean age 31 +/- 14 years, 16 men) and 31 controls were
      examined. Blood flow was recorded in the aorta near the aortic valve and
      immediately after in the descending aorta with simultaneous electrocardiography.
      PWV was calculated by dividing the distance between the two sample volume
      positions (D) by the time difference (TD) between the intervals from the QRS
      start to the ascending and descending aortic flow onsets. B-stiffness was also
      measured. RESULTS: TD (described in "Methods" section) and, aortic arch length
      were significantly increased in MFS patients, P < 0.001. Thus, PWV values were
      significantly higher in patients when compared with controls, 7.20 m/s (5.12,
      9.43) versus 4.64 m/s (3.37, 6.24), P < 0.001. B-stiffness was also significantly
      increased in MFS patients; 5.15 (3.69, 7.65) versus 2.44 (1.82, 3.66), P < 0.001.
      Multiple regression analysis showed a positive association with MFS diagnosis and
      age, (P = 0.002 and 0.009, respectively). Reproducibility of PWV measurements was
      <5%. CONCLUSIONS: AoS was significantly higher in MFS patients as expected. Our
      data demonstrated that PWV measurements can be performed, in the absence of
      serious musculoskeletal abnormalities in MFS adults, as part of a cardiac
      ultrasound scan. This technique can be helpful in diagnosis and management in
      MFS.

PMID- 21198822
TI  - Giant pedunculated thrombus with normal left ventricular systolic function
      mimicking myxoma.
AB  - A 74-year-old woman with a history of essential thrombocythemia was admitted to
      the Coronary Care Unit because of atypical chest pain. The transthoracic
      echocardiogram showed normal left ventricular (LV) diameter and preserved
      regional and global systolic function. A pedunculated mobile mass measuring 25 mm
      * 14 mm was visualized in the LV cavity, attached to the midanterior wall.
      Because of the typical echocardiographic appearance, a myxoma was suspected. The
      patient evolved with left hemiparesis and negative T-waves in the
      electrocardiogram. Left ventriculotomy with excision of the ventricular mass was
      performed. Histopathological examination revealed an organized thrombus.

PMID- 21198823
TI  - Can dobutamine stress echocardiography induce cardiac troponin elevation?
AB  - BACKGROUND: Elevation of cardiac troponin (cTn) is considered specific for
      myocardial damage. Elevated cTn and echocardiogrpahic documentation of wall
      motion abnormalities (WMAs) that were recorded after extreme physical effort
      raise the question whether dobutamine stress echo (DSE), can also induce
      elevation of troponin. METHODS: we prospective enrolled stable patients (age >18
      years) referred to DSE. The exam was performed under standardized conditions.
      Blood samples for cTnI were obtained at baseline and 18-24 hours after the test.
      We aimed to compare between the clinical and echocardiographic features of
      patients with elevated cTnI and those without cTnI elevations. RESULTS: Fifty
      seven consecutive patients were included. The average age was 64.4 +/- 10.7, 73%
      of the patients were males, and nearly half of the patients were known to have
      ischemic heart disease. Two of the patients were excluded due to technical
      difficulty. No signs of ischemia were recorded in 25 (45.4%). Among the patients
      with established ischemia on DSE, 12 (22%) had mild ischemia, 13 (23.6%) had
      moderate and 5 (9%) had severe ischemia. Angiography was performed in 13 (26%) of
      the patients, of which 7 had PCI and one was referred to bypass surgery. None of
      the patients had elevated cTnI 18-24 hours after the DSE. CONCLUSIONS: Our
      results indicate that there is no elevation of cTn despite the occurrence of
      significant WMAs on DSE. We conclude that cTnI cannot be used as an additional
      diagnostic tool during pharmacological stress test performed to evaluate the
      presence and severity of ischemia.

PMID- 21198824
TI  - Echocardiographic evaluation of calcific aortic stenosis in the older adult.
AB  - Aortic stenosis is the most predominant valvular pathology occurring in older
      adults with an expected increase over time. Multiple comorbidities and highly
      variable clinical presentations which characterize the aging population
      necessitate the use of echocardiography in the assessment of valvular structure
      and real time hemodynamic evaluation. This article reviews the pathophysiology
      and clinical presentation of aortic stenosis in this unique population and the
      critical role of various echocardiographic modalities. The value of real time
      three-dimensional real time echocardiography in the assessment and management of
      aortic stenosis in older adults is emphasized.

PMID- 21198825
TI  - Melatonin ameliorates ischemic-like injury-evoked nitrosative stress: Involvement
      of HtrA2/PED pathways in endothelial cells.
AB  - Peroxynitrite contributes to diverse cellular stresses in the pathogenesis of
      ischemic complications. Here, we investigate the downstream effector signaling
      elements of nitrosative stress which regulate ischemia-like cell death in
      endothelial cells and protective effect of melatonin. When the mitochondrial
      membrane potential (DeltaPsim) of oxygen-glucose deprivation (OGD)-treated cells
      was assessed using the fluorescent probe 5,5',6,6'-tetrachloro-1,1',3,3'
      tetraethylbenzimidazol -carbocyanine iodide, we observed spontaneous changes in
      peroxynitrite formation. Concomitantly, western blot and confocal microscopy
      analyses indicated that prolonged OGD exposure initiates the release of
      mitochondrial HtrA2 and dramatically decreases phosphoprotein enriched in
      astrocytes (PED or PEA-15) protein levels. Consistently, cultured endothelial
      cells treated with peroxynitrite (1-50 MUm) exhibited a concentration-dependent
      release of mitochondrial HtrA2 and concomitant PED degradation in vitro. Notably,
      HtrA2 activation coincided with increased nitrotyrosine immunoreactivity in
      microvessels of rats following microsphere embolism. Additionally, the protective
      effect of PED overexpression in OGD-induced apoptosis was abolished by
      transfection with the PED(S104A/S116A) mutant. Furthermore, the effect of
      melatonin, an potential antioxidant, on endothelial apoptotic cascade was
      examined in OGD-evoked nitrosative stress. Our data showed that the application
      of melatonin provided significant protection against OGD-induced peroxynitrite
      formation and mitochondrial HtrA2 release, accompanied with a decrease in
      degradation PED and x-linked inhibitor of apoptosis protein, which is associated
      with activation of the caspase cascade. Taken together, the protective effect of
      melatonin is likely mediated, in part, by inhibition of peroxynitrate-mediated
      nitrosative stress, which in turn relieves imbalance of mitochondrial HtrA2-PED
      signaling and endothelial cell death.

PMID- 21198826
TI  - Abstracts of the Second Excellence in Paediatrics Conference. December 2-4, 2010,
      London, United Kingdom.

PMID- 21198827
TI  - Helicobacter pylori infection and gastritis: the Systematic Investigation of
      gastrointestinaL diseases in China (SILC).
AB  - BACKGROUND AND AIM: Helicobacter pylori infection remains common in East Asia,
      though its prevalence is decreasing in Western countries. H. pylori-related
      atrophic gastritis (AG) may reduce the likelihood of gastroesophageal reflux
      disease (GERD). We investigated the prevalence of H. pylori infection and AG and
      their association with endoscopic findings and symptom-defined GERD in Shanghai.
      METHODS: A representative random sample of 3600 Shanghai residents aged 18-80
      years was invited to complete a general information questionnaire and a Chinese
      version of the Reflux Disease Questionnaire, to provide blood samples for H.
      pylori serology and pepsinogen (PG) I/II assay (to detect AG, defined as PGI < 70
      ug/L and/or PGI/PGII < 7), and to undergo endoscopy. Odds ratios (ORs) and 95%
      confidence intervals (CIs) were calculated by multivariate logistic regression.
      RESULTS: A total of 1022 Shanghai residents underwent endoscopy and were valid
      for inclusion in the study. Of these, 71.7% tested positive for H. pylori, 63.8%
      had AG and 30.5% had moderate/severe AG (PGI < 50 ug/L and/or PGI/PGII < 5).
      Helicobacter pylori infection was equally common in all age groups. Severity of
      AG increased with age in women. Reflux esophagitis was inversely associated with
      AG (OR, 0.23 [CI, 0.09-0.55] for moderate/severe AG compared with no H. pylori or
      gastritis). However, symptom-defined GERD showed no clear association with AG.
      CONCLUSIONS: Helicobacter pylori infection and AG are very common in Shanghai,
      and the infection is acquired early in life. Atrophic gastritis is inversely
      associated with reflux esophagitis but is not significantly associated with
      symptom-defined GERD.

PMID- 21198828
TI  - Application of the HALF index obviates the need for liver biopsy in half of all
      patients with chronic hepatitis B.
AB  - BACKGROUND AND AIMS: Transient elastography (TE) is useful for predicting the
      fibrosis stage, but it is unsatisfactory as a substitute for liver biopsy,
      especially in patients with chronic hepatitis B (CHB). This study was performed
      to establish a reliable model for predicting significant fibrosis (SF) in
      patients with CHB. METHODS: All CHB patients who were admitted to undergo liver
      biopsy were enrolled. They were randomly classified into either a training set (n
      = 139) or a validation set (n = 69). A model for predicting SF was established in
      the training set and validated in the validation set. Low and high cutoff values
      (COVs) were chosen for sensitivity >= 99% and specificity >= 99%, respectively.
      RESULTS: A total of 208 patients were enrolled. Age was 39 +/- 12 years and 149
      (71.6%) were men. In the training set, liver stiffness values and serum
      haptoglobin, apolipoprotein A1, and alpha2-macroglobulin levels were independent
      predictors of SF on multivariate analysis. These variables were used to construct
      a novel model, called the HALF index. The area under the receiver operating
      characteristics curve of the HALF index for predicting SF was significantly
      higher than that of TE alone (0.915 vs 0.877, P = 0.010). Using low and high COVs
      of the HALF index, it appears that approximately half (47.1%) of patients could
      avoid liver biopsy, with an associated accuracy of 99.0%. CONCLUSION: A
      combination of liver stiffness and serum markers identified SF with a high degree
      of accuracy. Approximately half of all patients with CHB could avoid liver biopsy
      through the utilization of the HALF index.

PMID- 21198829
TI  - NSAIDs are a significant risk factor for colonic diverticular hemorrhage in elder
      patients: evaluation by a case-control study.
AB  - BACKGROUND AND AIM: Diverticular bleeding is a common cause of lower
      gastrointestinal hemorrhage. Several factors, including use of non-steroidal anti
      inflammatory drugs (NSAIDs), antithrombotic agents and arteriosclerosis, could be
      risk factors. The aim of this study is to identify these risk factors. METHODS:
      Between January 2000 and December 2008, 51 patients among 178 acute lower
      gastrointestinal hemorrhages who visited Saga Medical School were diagnosed as
      colonic diverticular hemorrhage, established by emergency endoscopy and
      diagnostic criteria. Gender and age matched control cases were selected from
      patients of other diseases hospitalized during the same period. We evaluated by
      using logistic regression analysis the influences of comorbidities such as
      cerebrovascular disease, ischemic heart disease, hypertension, hyperlipidemia,
      diabetes mellitus, chronic kidney disease, and osteoporosis, medications
      including NSAIDs and antithrombotic agents, and habits of smoking, alcohol, and
      chronic constipation. RESULTS: Fifty one patients out of 178 acute lower
      gastrointestinal bleeding (28.7%) were diagnosed as diverticular hemorrhage,
      which was the most common cause of lower gastrointestinal hemorrhage. Sex ratio
      of men versus women for colonic diverticular hemorrhage was 35:16. NSAIDs were a
      significant risk factor for colonic diverticular hemorrhage in elder patients
      (odds ratio [OR] = 7.492, 95% CI: 1.516-37.024, P = 0.0135). Hypertension and
      hyperlipidemia had significant association with diverticular hemorrhage among
      patients younger than 65 years old. This study also indicated that use of NSAIDs
      was a risk factor for re-bleeding (OR = 5.4, 95% CI: 1.01-28.78, P = 0.048).
      CONCLUSION: This case-control study revealed that the use of NSAIDs was a
      significant risk factor for colonic diverticular hemorrhage in elder patients. In
      addition, use of NSAIDs is a risk factor for re-bleeding from colonic
      diverticula.

PMID- 21198830
TI  - Extended indication of endoscopic resection for mucosal early gastric cancer:
      analysis of a single center experience.
AB  - BACKGROUND: Endoscopic resection (ER) has become an important therapeutic option
      for early gastric cancer (EGC). Some investigators have suggested that this
      indication should be extended. We aimed to compare the extended indication of ER
      for intramucosal EGC based on data from a large, single-center study. METHODS: We
      assessed lymph node metastasis (LNM) status in 1721 intramucosal EGC patients who
      underwent surgery to evaluate the potential of extension of the ER. We
      investigated LNM according to Japanese extended criteria; differentiated mucosal
      cancers irrespective of ulcer less than 30 mm (Criteria I); differentiated
      mucosal cancers without ulceration irrespective of tumor size (Criteria II),
      undifferentiated less than 20 mm without ulceration (Criteria III). We also tried
      to find the groups which have no and minimal risk of lymph node metastasis.
      RESULTS: The rate of LNM of mucosal cancer was 2.6% (45/1721). There was minimal
      lymph nodal metastasis risk for criteria I (0.28%, 2/726, 95% Confidence Interval
      [CI], 0-0.66%), and criteria II (0.23%, 2/882, 95% CI, 0-0.54%). For criteria
      III, there was significant lymph node metastasis risk (1.15%, 3/261, 95% CI, 0
      2.44%). There was no lymph node metastasis in differentiated mucosal cancer less
      than 20 mm irrespective of ulcer (0%, 0/501, 95% CI 0-0.73%). The differentiated
      mucosal cancer group irrespective of ulcer and tumor size have a minimal risk of
      metastasis (0.43%, 4/941, 95% CI, 0-0.84%) CONCLUSION: Our data support extension
      of the ER indication for the differentiated mucosal EGC. However,
      undifferentiated lesions without ulceration and smaller than 20 mm were
      associated with significant metastasis.

PMID- 21198831
TI  - Biomarkers of liver fibrosis.
AB  - Fibrosis prediction is an essential part of the assessment and management of
      patients with chronic liver disease. Blood-based biomarkers offer a number of
      advantages over the traditional standard of fibrosis assessment of liver biopsy,
      including safety, cost-savings and wide spread accessibility. Current biomarker
      algorithms include indirect surrogate measures of fibrosis, including
      aminotransaminases and platelet count, or direct measures of fibrinogenesis or
      fibrinolysis such as hyaluronic acid and tissue inhibitor of metalloproteinase-1.
      A number of algorithms have now been validated across a range of chronic liver
      disease including chronic viral hepatitis, alcoholic and non-alcoholic fatty
      liver disease. Furthermore, several models have been demonstrated to be dynamic
      to changes in fibrosis over time and are predictive of liver-related survival and
      overall survival to a greater degree than liver biopsy. Current limitations of
      biomarker models include a significant indeterminate range, and a predictive
      ability that is limited to only a few stages of fibrosis. Utilization of these
      biomarker models requires knowledge of patient co-morbidities which may produce
      false positive or negative results in a small proportion of individuals.
      Furthermore, knowledge of the underlying prevalence of fibrosis in the patient
      population is required for interpretation of the positive or negative predictive
      values of a test result. Novel proteins identified by proteomic technology and
      genetic polymorphisms from genome association studies offer the possibility for
      further refinement and individualization of biomarker fibrosis models in the
      future.

PMID- 21198832
TI  - Optometrists get their wings.

PMID- 21198833
TI  - The 13th Biennial Scientific Meeting in Optometry and the 7th Optometric
      Educators Meeting go online.

PMID- 21198834
TI  - Multiplicative rating scales do not enable measurement of vision-related quality
      of life.
AB  - PURPOSE:   Many questionnaires for the measurement of visual impairment exist.
      One, the Houston Vision Assessment Test (HVAT), takes a different approach: the
      patient is asked to rate overall impairment and the proportion attributed to
      vision, then through multiplication the visual and non-visual (physical)
      impairments are calculated. The purpose of this study was to determine whether
      the scores derived from this approach can be considered to be measures. METHODS: 
      The participants were 193 cataract patients awaiting surgery (mean age 74.1 +/-
      9.8 years, 54 per cent female and 53.6 per cent were awaiting first eye surgery),
      who self-administered the HVAT, which consists of 10 questions, whereby
      impairment on each activity and the proportion attributable to vision is rated.
      Therefore, total, visual and physical impairments are calculated. For each
      question, multiplying the impairment (five response categories) by the proportion
      due to eyesight (five categories) gives 10 possible levels of visual impairment.
      Assessment of the multiplicative rating scales included frequency of category use
      and hierarchical ordering of response categories using category thresholds.
      Summary statistics of Rasch analysis were generated for the rating scale and
      overall questionnaire performance. RESULTS:   In the multiplicative scale, higher
      response categories were under-utilised and thresholds were disordered,
      indicating that the categories did not function as intended. Some of the
      dysfunction arose from disordered thresholds in the 'proportion due to eyesight
      scale', but repairing this gave little improvement to the multiplicative scale.
      The ill-defined nature of the disordered categories precluded further repair by
      combining categories. Measurement precision, as indicated by person separation
      reliability, was poor (0.70). CONCLUSION:   Rasch analysis demonstrated that the
      categories of the multiplied rating scale of the HVAT were not ordered, as the
      user would expect; this precludes measurement. This provides evidence against the
      use of multiplicative rating scales in quality-of-life questionnaires. It would
      be better to use a single rating scale for each construct of interest.

PMID- 21198835
TI  - Community-based diabetic retinopathy screening in Hong Kong: ocular findings.
AB  - BACKGROUND:   Diabetic retinopathy is one of the most common causes of blindness.
      Timely retinal evaluation is known to prevent or minimise visual loss. This study
      compared the prevalence of ocular disorders in patients who have and have not
      undergone a retinal examination since diagnosis of their type 2 diabetes mellitus
      (T2DM). Such data might be useful for planning purposes by health care
      authorities and agencies in Hong Kong. METHODS:   Patients with T2DM aged 30
      years or over presented for standardised interviews and screening for diabetic
      retinopathy. The presence of ocular disorders was recorded and the severity of
      the retinopathy, if any, was graded using the Early Treatment Diabetic
      Retinopathy Study (ETDRS) classification. RESULTS:   For the 1058 subjects who
      participated in this study, the mean age at examination was 61.8 +/- 10.5 (SD)
      years (range, 31-93 years). For the 891 subjects with known diabetes for one year
      or longer, 62.7 per cent had never undergone an evaluation for diabetic
      retinopathy since diagnosis of their T2DM. Of the 891 subjects, gradable fundus
      photographs were available for 853 subjects and nearly 2.0 per cent of these had
      sight-threatening retinopathy based on the ETDRS classification. Those who had
      not had an eye examination since diagnosis of their T2DM were more likely to have
      sight-threatening retinopathy than those who had a retinal evaluation (2.6 versus
      0.6 per cent; p = 0.04). CONCLUSION:   In our sample, over 60 per cent of
      patients with T2DM for one year or longer had not had a retinal assessment since
      diagnosis. The risk of developing sight-threatening diabetic retinopathy appears
      to be higher for those who have not had a retinal assessment.

PMID- 21198836
TI  - Refractive errors in students from Middle Eastern backgrounds living and
      undertaking schooling in Australia.
AB  - BACKGROUND:   Environmental factors associated with schooling systems in various
      countries have been implicated in the rising prevalence of myopia, making the
      comparison of prevalence of refractive errors in migrant populations of interest.
      This study aims to determine the prevalence of refractive errors in children of
      Middle Eastern descent, raised and living in urban Australia but actively
      maintaining strong ties to their ethnic culture, and to compare them with those
      in the Middle East where myopia prevalence is generally low. METHODS:   A total
      of 354 out of a possible 384 late primary/early secondary schoolchildren
      attending a private school attracting children of Middle Eastern background in
      Melbourne were assessed for refractive error and visual acuity. A Shin Nippon
      open-field NVision-K5001 autorefractor was used to carry out non-cycloplegic
      autorefraction while viewing a distant target. For statistical analyses students
      were divided into three age groups: 10-11 years (n = 93); 12-13 years (n = 158);
      and 14-15 years (n = 102). RESULTS:   All children were bilingual and classified
      as of Middle Eastern (96.3 per cent) or Egyptian (3.7 per cent) origin. Ages
      ranged from 10 to 15 years, with a mean of 13.17 +/- 0.8 (SEM) years. Mean
      spherical equivalent refraction (SER) for the right eye was +0.09 +/- 0.07 D
      (SEM) with a range from -7.77 D to +5.85 D. The prevalence of myopia, defined as
      a spherical equivalent refraction 0.50 D or more of myopia, was 14.7 per cent.
      The prevalence of hyperopia, defined as a spherical equivalent refraction of
      +0.75 D or greater, was 16.4 per cent, while hyperopia of +1.50 D or greater was
      5.4 per cent. A significant difference in SER was seen as a function of age;
      however, no significant gender difference was seen. CONCLUSIONS:   This is the
      first study to report the prevalence of refractive errors for second-generation
      Australian schoolchildren coming from a predominantly Lebanese Middle Eastern
      Arabic background, who endeavour to maintain their ethnic ties. The relatively
      low prevalence of myopia is similar to that found for other metropolitan
      Australian school children but higher than that reported in the Middle East.
      These results suggest that lifestyle and educational practices may be a
      significant influence in the progression of myopic refractive errors.

PMID- 21198837
TI  - Innovative strategies for adaptation to loss of vision.

PMID- 21198839
TI  - Paediatric hyperopia, accommodative esotropia and refractive amblyopia.

PMID- 21198838
TI  - Imaging inadvertent Descemet's membrane break secondary to cataract surgery.

PMID- 21198840
TI  - Macular hole formation following phacoemulsification cataract surgery.

PMID- 21198843
TI  - Mediastinal liposarcoma.
AB  - A 64-year-old male underwent surgical resection of a large liposarcoma of the
      mediastinum. The management of this unusual tumor is the subject of this case
      report.

PMID- 21198842
TI  - Pseudoxanthoma elasticum, ocular manifestations, complications and treatment.
AB  - Pseudoxanthoma elasticum (PXE), also known as Groenblad syndrome, is an inherited
      disorder characterised by mineralisation and fragmentation of elastic fibres in a
      number of organs including the skin, eyes and arterial blood vessels. The
      clinical manifestations of PXE centre on three major organ systems: skin,
      cardiovascular system and the eyes. This review focuses on the ocular
      manifestations of pseudoxanthoma elasticum, namely, peau d'orange, angioid
      streaks and choroidal neovascularisation, the clinical course of patients, the
      diagnostic approaches and current therapeutic strategies, such as laser
      photocoagulation whether transpupillary thermotherapy or photodynamic therapy,
      macular translocation surgery and anti-vascular endothelial growth factor
      treatment.

PMID- 21198844
TI  - Idiopathic left atrial appendage rupture.
AB  - Cardiac rupture is mainly caused by myocardial infarction or blunt chest trauma.
      We present a case of idiopathic left atrial appendage rupture.

PMID- 21198845
TI  - Resecting and nonresecting techniques for posterior mitral leaflet prolapse.
AB  - BACKGROUND: Posterior leaflet (PL) prolapse is commonly treated with quadrangular
      resection, but nonresecting techniques were proposed as an alternative. We
      evaluated our experience to identify specific indications to nonresecting
      techniques. METHODS: From March 2006 to February 2009, 60 patients were treated
      for PL prolapse, 21 using resecting (group R), and 39 nonresecting (group NR)
      techniques. Patients in group R had fibroelastic deficiency with isolated P2
      prolapse and P1 or P3 (or both) thin or short (n = 15); need of excessive P2
      resection (more than 1/3 of the posterior annulus) (n = 10); dominant or
      codominant circumflex artery (n = 10). Some of them were young and were operated
      on without preoperative coronary angiography (n = 4). RESULTS: One patient (1.7%)
      in group R died during the first 30 days after surgery. Three-year survival was
      89.6 +/- 4.5, similar in both groups. A postoperative echocardiogram was obtained
      20 +/- 6 months after surgery in every survivor. Mitral regurgitation decreased
      significantly soon after surgery without any significant modification at follow
      up in both groups. CONCLUSIONS: nonresecting techniques provide good midterm
      results, similar to resecting ones. To resect or not resect part of the PL has,
      in our personal practice, its own indications and contraindications. Extensive
      use of artificial chords and reduction of PL height, when indicated, is able to
      provide other tools to safely expand mitral repair for PL prolapse.

PMID- 21198846
TI  - Constraints to species' elevational range shifts as climate changes.
AB  - Predicting whether the ranges of tropical species will shift to higher elevations
      in response to climate change requires models that incorporate data on topography
      and land use. We incorporated temperature gradients and land-cover data from the
      current ranges of species in a model of range shifts in response to climate
      change. We tested four possible scenarios of amphibian movement on a tropical
      mountain: movement upslope through and to land cover suitable for the species;
      movement upslope to land-cover types that will not sustain survival and
      reproduction; movement upslope to areas that previously were outside the species'
      range; and movement upslope to cooler areas within the current range. Areas in
      the final scenario will become isolated as climate continues to change. In our
      scenarios more than 30% of the range of 21 of 46 amphibian species in the
      tropical Sierra Nevada de Santa Marta is likely to become isolated as climate
      changes. More than 30% of the range of 13 amphibian species would shift to areas
      that currently are unlikely to sustain survival and reproduction. Combined, over
      70% of the current range of seven species would become thermally isolated or
      shift to areas that currently are unlikely to support survival and reproduction.
      The constraints on species' movements to higher elevations in response to climate
      change can increase considerably the number of species threatened by climate
      change in tropical mountains.

PMID- 21198847
TI  - Safety and efficacy of transjugular renal biopsy performed by interventional
      nephrologists.
AB  - Obtaining renal tissue is often critical in the diagnosis and management of
      patients with renal disease of unknown etiology. Bleeding diathesis, liver
      disease, and obesity are common contraindications for percutaneous renal biopsy.
      In high-risk patients, transjugular renal biopsy is believed to be a safe and
      effective procedure. This study reports the experience of an academic
      interventional nephrology program with performing transjugular renal biopsy. We
      performed a retrospective observational study of 23 patients with either acute or
      chronic kidney disease with contraindications for percutaneous renal biopsy. All
      transjugular renal biopsies were performed by interventional nephrologists at our
      university. We studied the efficacy and safety of transjugular renal biopsy in
      these patients. Twenty out of 23 (87%) of the procedures yielded adequate tissue
      for pathologic diagnosis. Three (13%) patients required blood transfusions, none
      required coil embolization or nephrectomy, and there were no deaths. Even though
      performing transjugular renal biopsy requires considerable technical expertise
      and must be performed in an interventional radiology suite, it can be safely and
      effectively performed by well-trained interventional nephrologists to achieve
      pathological diagnosis.

PMID- 21198848
TI  - Serum N-terminal pro-B-type natriuretic peptide levels at the time of hospital
      admission predict of microvascular obstructions after primary percutaneous
      coronary intervention for acute ST-segment elevation myocardial infarction.
AB  - BACKGROUND: Significant microvascular obstruction (MVO) during primary
      percutaneous coronary intervention (PCI) may suggest severe myocardial damage.
      The predictive value of N-terminal pro-B-type natriuretic peptide levels (NT
      proBNP) for MVO has not been previously evaluated. HYPOTHESIS: The purpose of the
      study was to determine whether NT-proBNP levels measured upon hospital admission
      of ST-segment elevation myocardial infarction (STEMI) patients receiving primary
      PCI have predictive value for MVO. METHODS: NT-proBNP levels were obtained upon
      admission to the emergency department, for 41 acute STEMI patients. Cardiac
      contrast-enhanced magnetic resonance imaging (CE-MRI) was performed within 4 days
      after PCI. The optimal cut-off value to predict grade 3 MVO was determined using
      a receiver operating characteristic (ROC) curve. Multivariate regression analysis
      was performed to determine predictors for grade 3 MVO. RESULTS: MVO grade
      correlated with left ventricular ejection fraction (LVEF; r =-0.383, P = 0.013),
      peak serum creatine kinase MB iso-enzyme (CK-MB; r = 0.470, P = 0.002), and NT
      proBNP levels (r = 0.357, P = 0.022). The optimal cut-off value to predict grade
      3 MVO was an NT-proBNP level of >=80 pg/mL. Multivariate regression analysis,
      including LVEF, peak CK-MB, and an NT-proBNP >=80 pg/mL revealed that only an NT
      proBNP >=80 pg/mL was an independent factor related to grade 3 MVO. CONCLUSION:
      NT-proBNP levels upon hospital admission have a predictive value for MVOs.
      Further study is needed to determine if protective treatment strategies are
      warranted in STEMI patients with high NT-proBNP levels at presentation.

PMID- 21198849
TI  - Novel antiplatelet agent ticagrelor in the management of acute coronary syndrome.
AB  - Current clinical guidelines recommend dual antiplatelet agents namely aspirin and
      clopidogrel for the treatment of patients suffering from acute coronary syndrome
      (ACS). But the efficacy of clopidogrel is variable as it is a pro-drug, which has
      to be metabolized to become an active drug thus exhibiting variable platelet
      inhibition, increases risk of bleeding, stent thrombosis, and ischemia. To
      overcome this limitation, prasugrel was developed with increased antiplatelet
      activity thereby reducing the risk of myocardial ischemia and stent thrombosis.
      This action of prasugrel was associated with an increased risk of major bleeding.
      Finally, a novel reversible and direct-acting oral adenosine diphosphate (ADP)
      receptor antagonist, ticagrelor was developed that showed consistent and
      increased P2Y12 inhibition with similar incidence of bleeding but greater
      reduction in cardiac events compared to clopidogrel. The focus of this article is
      to review ticagrelor as a new class of P2Y12 inhibitor.

PMID- 21198850
TI  - Late catch-up phenomenon associated with stent fracture after sirolimus-eluting
      stent implantation: incidence and outcome.
AB  - OBJECTIVE: To examine the long-term outcome of the stent fracture (SF) and the
      potential predictive factors contributing to in-stent restenosis (ISR) in the
      fractured stent. BACKGROUND: The SF is thought to be a higher risk of ISR in drug
      eluting stent, although SF does not always develop ISR. METHODS: The consecutive
      1,228 de novo lesions in 1,079 patients who underwent sirolimus-eluting stents
      implantation and assessed by 8 months follow-up coronary angiography were
      retrospectively analyzed. RESULTS: One hundred and seventeen SFs (9.5%) were
      identified in 100 patients and 22 (18.8%) SFs revealed ISR at the first follow
      up. In addition, 16 (13.7%) developed new ISRs from 95 residual SFs without ISR
      prior to the second follow-up. Overall, 38 (32.5%) of all 117 SFs developed ISR,
      and 16 (42.1%) of 38 SFs occurred in a late phase beyond the first 8 months
      follow-up. A higher risk of ISR in the SF site was associated with the chronic
      total occlusion (ISR vs. no ISR: 34.2% vs. 16.5%, P = 0.0304), calcified lesions
      (55.3% vs. 34.2%, P = 0.0299), and correspondence 89.5% versus 43.0%, P < 0.0001
      (SF site occurring at the original target lesion site) in the univariate
      analysis. The correspondence was identified as the only strong predictive factor
      for ISR at the SF site according to a multivariate logistic regression analysis
      (odds ratio 12.6, 95% confidence interval 3.82-53.5, P < 0.0001). CONCLUSIONS: SF
      occurring at the site of the original target lesion was a strong independent
      predictor of ISR. This indicates the need for a careful, long-term follow-up in
      those situations, even when no significant ISR is initially detected.

PMID- 21198851
TI  - Optical coherence tomography: a new imaging modality for plaque characterization
      and stent implantation.
AB  - Optical coherence tomography (OCT) is a novel, catheter-based, invasive imaging
      system based on near-infrared light with high image resolution (15-20 MUm). The
      system allows for unparalleled imaging of the coronary artery lumen, plaque
      characterization, assessment of coronary stent strut apposition, neointimal
      coverage, vascular proliferative response, complications such as focal dissection
      or thrombus formation, and insight into the time course of stent endothelization.
      This review will describe the currently available developments in OCT technology
      and its application in both the clinical and research arenas.

PMID- 21198852
TI  - Effect of oversized partial postdilatation on coatings of contemporary durable
      polymer-based drug-eluting stents: a scanning electron microscopy study.
AB  - BACKGROUND:  Oversized postdilation of drug-eluting stents (DES) is often
      performed to avoid stent malapposition. In stents implanted in long lesion or
      major bifurcations, extremely oversized partial postdilation may be required,
      which exposes DES coating to extreme forces. This study aims to assess shape and
      incidence of coating irregularities on durable polymer-based DES following
      extremely oversized partial postdilatation. METHODS:  Fifteen DES samples (3 3.5
      mm stents of Cypher Select plus [Cordis Europa, Roden, the Netherlands], Taxus
      Liberte[Boston Scientific Corp., Natick, MA, USA], Endeavor Sprint [Medtronic
      Vascular, Santa Rosa, CA, USA], Endeavor Resolute [Medtronic Vascular, Santa
      Rosa, CA, USA], and Xience V [Abbott Vascular, Santa Clara, CA, USA]) were
      deployed in sterile water (37  degrees C) at 14 atm, followed by a proximal
      postdilation with noncompliant 5.0-mm balloons at 18 atm. Stents were then
      examined with scanning electron microscopy. RESULTS:  Thorough examination of a
      total of 660 scanning electron microscopic images demonstrated that shape and
      incidence of coating irregularities in the postdilated and/or transitional DES
      regions differed only mildly from the nonpostdilated regions. Cypher Select plus
      showed more peeling without bare metal aspect in the postdilated and transitional
      regions, and cracks were wider (P < 0.001) in the postdilated and transitional
      regions; in Taxus Liberte one additional irregularity (torn webbing) and more
      wrinkles were observed (P < 0.05 for both); in Endeavor Resolute wider cracks
      were found in the extremely postdilated region only (P < 0.001). Endeavor Sprint
      and Xience V showed no differences in shape or incidence of coating
      irregularities between oversized and nonoversized stent regions. CONCLUSIONS: 
      Bench side assessment of five contemporary durable polymer-based DES with
      scanning electron microscopy suggests that even very aggressive stent
      postdilatation results in no more than mild differences in coating irregularities
      between postdilated and nonpostdilated stent regions. 

PMID- 21198853
TI  - Percutaneous atrial shunt closure using the novel Occlutech Figulla device: 6
      month efficacy and safety.
AB  - BACKGROUND: The Occlutech Figulla Occluder is a new innovative device for
      percutaneous closure of a patent foramen ovale (PFO) and an atrial septum defect
      (ASD). We describe the safety and efficacy of this new device at 6-month follow
      up. METHODS: All 82 consecutive patients (51% female, mean age 49.0 +/- 13.6
      years) who underwent percutaneous PFO (n = 48) or ASD (n = 34) closure between
      October 2008 and October 2009 were included. RESULTS: Implantation success was
      100%. The in-hospital complications were two new onset supraventricular
      tachycardia (SVT) (2.4%, both ASD patients), nine minimal groin hematoma's
      (11.0%, 4 PFO and 5 ASD patients), and one transient ST elevation during the
      procedure (1.2%, ASD patient). During 6 months follow-up (n = 79), no major
      complications or reoccurrences of cerebral thrombo-embolic events did occur.
      Seven patients (8.9%, 6 PFO and 1 ASD patient) experienced a new SVT. One patient
      developed a recurrent cerebral hemorrhage 5 months after ASD closure, which
      appeared not to be related to the procedure. Using contrast transthoracic
      echocardiography 6 months after PFO closure (n = 45), a residual shunt was
      present in 30.2% of the patients (small 25.6%, moderate 4.6%, severe 0%). In the
      ASD group (n = 34), a residual shunt was observed in 32.5% (small 17.7%, moderate
      14.7%, severe 2.9%). CONCLUSION: The Occlutech Figulla Occluder appears to be
      easy to use, effective, and safe for percutaneous closure of PFO and ASD. We
      report a low complication rate but a relative high percentage of small residual
      shunts 6 months after closure.

PMID- 21198854
TI  - Value of liver stiffness measured by transient elastography in the liver
      transplant pre-operative evaluation of the potential deceased liver donors:
      preliminary study.
AB  - The selection of a liver graft is crucial for the success of a transplantation.
      One of the determinant factors in the selection of a liver graft of quality is to
      assess the degree of steatosis. The aim of this study was to evaluate the
      feasibility of a FibroScan((r)) during the liver retrieval procedure and to
      determine the interest of measuring liver stiffness (LS) using the FibroScan((r))
      as a criterion of objective assessment in the pre-donation selection of liver
      grafts. Of 16 FibroScan((r)) performed on 16 livers of donors meeting
      conventional French criteria for the selection of liver grafts, the LS values
      were considered as abnormal in three donors (18.75%). The correspondence with the
      histologic analysis of the biopsies in terms of elevated steatosis was excellent.
      For 13 other liver grafts, the values of LS were normal as were the histologic
      analyses of the biopsies. A supplementary multicenter study is required in order
      to position the transient elastography as the objective examination in the pre
      operative selection of liver grafts.

PMID- 21198855
TI  - The "generic" effect of food on tacrolimus pharmacokinetics.

PMID- 21198856
TI  - Honoring the contract with our patients: outcome after repeated re
      transplantation of the liver.
AB  - The aim of this study was to describe the outcome after repeated orthotopic liver
      re-transplantations (re-OLT) in a population of adults and children, and to
      determine whether such repeated re-transplantations are an effective treatment or
      should be considered futile. In a consecutive series of 867 patients, 628 adults
      and 239 children, who underwent OLT at the University Medical Center Groningen,
      23 patients (2.7%), 10 adults and 13 children, underwent more than two re
      transplantations of the liver between March 1979 and October 2008. All 23
      patients had a second re-transplantation, and seven of them received a third
      transplant. The overall actuarial patient survival at 1, 5, and 10 yr after
      primary OLT was 96%, 87%, and 71%, respectively. The overall actuarial patient
      survival after the second re-OLT was 78%, 73%, and 67%, respectively. Sixteen
      patients (70%) survived long term. However, for the 23 repeated re
      transplantation patients, 76 grafts were used. In a simulation calculation, it
      was shown that honoring the initial commitment to the 23 patients ultimately led
      to more surviving patients and less death than if treatment of the original
      patients was stopped after the first re-transplantation and the remaining grafts
      were allocated to other primary graft recipients.

PMID- 21198857
TI  - Effect of education on racial disparities in access to kidney transplantation.
AB  - Higher education level might result in reduced disparities in access to renal
      transplantation. We analyzed two outcomes: (i) being placed on the waiting list
      or transplanted without listing and (ii) transplantation in patients who were
      placed on the waiting list. We identified 3224 adult patients with end-stage
      renal disease (ESRD) in United States Renal Data System with education
      information available (mean age of ESRD onset of 57.1 +/- 16.2 yr old, 54.3% men,
      64.2% white, and 50.4% diabetics). Compared to whites, fewer African Americans
      graduated from college (10% vs. 16.7%) and a higher percentage never graduated
      from the high school (38.6% vs. 30.8%). African American race was associated with
      reduced access to transplantation (hazard ratio [HR] 0.70, p < 0.001 for wait
      listing/transplantation without listing; HR 0.58, p < 0.001 for transplantation
      after listing). African American patients were less likely to be wait
      listed/transplanted in the three less-educated groups: HR 0.67 (p = 0.005) for
      those never completed high school, HR 0.76 (p = 0.02) for high school graduates,
      and HR 0.65 (p = 0.003) for those with partial college education. However, the
      difference lost statistical significance in those who completed college education
      (HR 0.75, p = 0.1). In conclusion, in comparing white and African American
      candidates, racial disparities in access to kidney transplantation do exist.
      However, they might be alleviated in highly educated individuals.

PMID- 21198858
TI  - Clinical and prognostic significance of apoptotic profile in patients with newly
      diagnosed nodal diffuse large B-cell lymphoma (DLBCL).
AB  - BACKGROUND: Apoptosis-related proteins might play an important role in the
      pathogenesis of lymphoma and sensibility to chemotherapy (CH) in patients with
      non-Hodgkin's lymphoma. We have analyzed the relationship between expression of
      two proapoptotic (CD95, caspase-3) and four antiapoptotic proteins (c-FLIP, bcl
      2, survivin, and XIAP) and clinical outcome of patients with nodal diffuse large
      B-cell lymphoma (DLBCL). METHODS: We have analyzed lymph node biopsy specimens
      obtained from 78 patients with newly diagnosed nodal DLBCL. The expression of
      apoptotic parameters was analyzed using the standard immunohistochemical method
      (antibodies against caspase-3, CD95, c-FLIP, XIAP, survivin, and bcl-2) on
      formalin-fixed and routinely processed paraffin-embedded lymph node specimens.
      The expression of immunohistochemical parameters has been evaluated
      semiquantitatively as a percentage of tumor cells. RESULTS: Immunoexpression of
      caspase-3, CD95, c-FLIP, survivin, XIAP, and bcl-2 has been found in 48 (61.5%),
      39 (50%), 45 (57.7%), 41 (52.6%), 43 (55.12%), and 39 (50.0%) patients,
      respectively. The therapy response was achieved in 53 (67.9%) patients. Besides
      numerous clinical parameters, survivin and XIAP positivity along with CD95
      negativity were found to be unfavorable factors for therapy response and shorter
      survival in univariate analysis. According to this finding, an 'apoptotic score'
      that includes unfavorable apoptotic parameters has been defined. In multivariate
      analysis, only International Prognostic Index (IPI) and apoptotic score remained
      independent prognostic predictors for the chance to reach the complete remission
      (P = 0.003 and P = 0.044, respectively) and longer overall survival (OS) (P =
      0.002 and P = 0.046, respectively). Significantly, the better response to
      immunochemotherapy (ICH) in comparison with CH has been achieved in patients with
      expression of caspase-3, c-FLIP, and survivin and in patients without the
      immunoexpression of XIAP. In addition, ICH was superior to CH in both bcl-2
      positive and bcl-2-negative patients. CONCLUSION: The results of this study
      showed that the dysregulation of apoptosis can appear on different places of
      apoptotic cascade in DLBCL. Apoptotic score is a more useful tool in predicting
      therapy response and OS of patients with DLBCL than single apoptotic parameters
      and along with IPI could help to identify a high-risk group of newly diagnosed
      nodal DLBCL.

PMID- 21198860
TI  - Normal pregnancy in a patient with beta-thalassaemia major receiving iron
      chelation therapy with deferasirox (Exjade(r)).

PMID- 21198859
TI  - The 8p11 myeloproliferative syndrome owing to rare FGFR1OP2-FGFR1 fusion.

PMID- 21198862
TI  - Absence of mutation in the RAB27B gene in patients with platelet delta-storage
      pool deficiency.

PMID- 21198861
TI  - Imatinib increases cytotoxicity of melphalan and their combination allows an
      efficient killing of chronic myeloid leukemia cells.
AB  - BCR/ABL positive cells are known to be resistant to DNA damage induced by
      chemotherapy while they are sensitive to imatinib (IM), a tyrosine kinase
      inhibitor (TKI). To evaluate whether this drug can increase the activity of
      cytotoxic drugs on BCR/ABL positive cells, we measured the toxicity of cytosine
      arabinoside (ARA-C), hydroxyurea (HU) and melphalan (MEL), after a pretreatment
      of 24 h with IM on K562 cell line. The highest cytotoxic effect was seen when the
      TKI was followed by MEL; our results indicate that inhibition of BCR/ABL activity
      by IM increased the cytotoxicity of MEL by favoring the DNA damage induced by
      this drug and by shortening the time for DNA repair at the G2/M checkpoint. A
      stronger activation of some genes involved in both intrinsic and extrinsic
      apoptotic pathways was also observed with IM/MEL combination compared to IM or
      MEL alone. The drugs association was further tested in a type of BaF3 cells
      (TonB.210) where the BCR-ABL expression is inducible by doxycycline; in this
      model it was confirmed that a reduction of BCR/ABL activity resulted in an
      increased susceptibility to the cytotoxic effect of MEL. Furthermore, we studied
      the effect of IM/MEL treatment on the proliferative potential of myeloid
      progenitors of six CML patients at diagnosis. The analysis of CFU-GM and BFU-E
      colonies demonstrated that the IM/MEL combination was more effective than IM
      alone in reducing the overall number of colonies and the number of copies of
      BCR/ABL. In conclusion, our work shows that inhibition of BCR/ABL activity
      increases the toxicity of MEL and allows an efficient killing of leukemic cells,
      suggesting that a clinical development of this approach could have therapeutic
      advantages for CML patients.

PMID- 21198863
TI  - Determination of platelet-bound glycoprotein-specific autoantibodies by flow
      cytometric immunobead assay in primary immune thrombocytopenia.
AB  - OBJECTIVES: Primary immune thrombocytopenia (ITP) is an autoimmune disorder
      characterized by premature platelet destruction induced by autoantibodies
      directed against platelet glycoproteins (GPs). Despite being a clinically
      important disorder, ITP lacks a feasible diagnostic assay for routine clinical
      use. This study was meant to evaluate a newly developed flow cytometric
      immunobead assay for determination of platelet-bound GP-specific autoantibodies
      in comparison with indirect monoclonal antibody-specific immobilization of
      platelet antigen (MAIPA) in the diagnosis of ITP. METHODS: Platelet-bound and
      plasma GPIIb/IIIa and GPIb/IX autoantibodies were determined by flow cytometric
      immunobead assay and indirect modified MAIPA, respectively. The average
      fluorescence level for platelet-bound, GP-specific autoantibodies was given as a
      ratio to three normal controls tested simultaneously. RESULTS: The median value
      of platelet-bound GPIIb/IIIa and GPIb/IX autoantibodies in ITP group were 3.09
      (range 0.78, 30.2) and 3.09 (range 0.72, 19.2), respectively, which were
      significantly higher than non-ITP group [1.01 (0.67, 5.59) and 1.01 (0.79, 5.56),
      respectively, P<0.001] and normal controls [1.02 (0.72, 1.76) and 1.03 (0.79,
      1.73), respectively, P<0.001]. The receiver-operating characteristics curve
      analysis showed an area under the curve of 0.895 for GPIIb/IIIa autoantibody and
      0.859 for GPIb/IX autoantibody, respectively. Combined detection of GPIIb/IIIa or
      GPIb/IX autoantibodies by flow cytometric immunobead assay showed a sensitivity
      of 82.11% for ITP diagnosis. CONCLUSION: This study demonstrated that
      determination of platelet-bound, GP-specific autoantibodies by flow cytometric
      immunobead assay was a convenient, sensitive, and specific test for the
      differential diagnosis of thrombocytopenic patients.

PMID- 21198864
TI  - Efficacy of pre-emptively used plerixafor in patients mobilizing poorly after
      chemomobilization: a single centre experience.
AB  - A significant proportion of patients with lymphoid malignancies are hard-to
      mobilize with a combination of chemotherapy plus granulocyte colony-stimulating
      factor (G-CSF) (chemomobilization). Plerixafor is a novel drug used to improve
      mobilization of blood stem cells. However, it has been studied mainly in
      association with G-CSF mobilization. We evaluated the efficacy of 'pre-emptive'
      use of plerixafor after chemomobilization in patients who seem to mobilize
      poorly. During a 15 month period, altogether 63 patients with lymphoid
      malignancies were admitted to our department for blood stem cell collection.
      Sixteen patients (25%) received plerixafor after the first mobilization due to
      the low blood (B) CD34(+) cell counts (n = 12) or poor yield of the first
      collection (n = 4). The median number of plerixafor injections was 1 (1-3). The
      median B-CD34(+) count after the first plerixafor dose was 39 * 10(6) /L (<1-81)
      with the median increase of fivefold. Stem cell aphaereses were performed in
      14/16 patients (88%) receiving plerixafor and a median of 2.9 * 10(6) /kg (1.6
      6.1) CD34(+) cells were collected with a median of one aphaeresis (1-3).
      Altogether 13/16 patients mobilized with a combination of chemomobilization and
      plerixafor received high-dose therapy with stem cell support and all engrafted.
      Pre-emptive use of plerixafor after chemomobilization is efficient and safe and
      should be considered in poor mobilizers to avoid collection failure. In patients
      with low but rising B-CD34(+) counts, the use of plerixafor might be delayed as
      late mobilization may occur. Further studies are needed to optimize patient
      selection and timing of plerixafor.

PMID- 21198865
TI  - Erythroleukaemia at second glance.

PMID- 21198866
TI  - Combining FDG-PET/CT with laboratory data yields superior results for prediction
      of relapse in multiple myeloma.
AB  - OBJECTIVES:   The precise role of positron emission tomography (PET/CT) for
      predicting relapse/progression in multiple myeloma remains uncertain. We compared
      the predictive values of PET/CT, concurrent laboratory testing (labs), and their
      combination in prediction of 12-month progression, as determined by current
      International Myeloma Working Group (IMWG) criteria. METHODS:   PET/CT and labs
      (serum chemistry, beta2-microglobulin, immunofixation, bone marrow biopsy, serum
      free light chains) were reviewed, and date of relapse/progression was determined
      by IMWG criteria. RESULTS:   The median time from therapy to PET/CT imaging was
      12.0 months (1.0-110) and median time to progression (TTP) was 29.8 months (1.6
      130+). Overall survival and survival-without-progression at last follow-up were
      84% and 49%, respectively. Sensitivity of PET/CT for predicting
      relapse/progression was lower than that of labs (0.67 vs. 0.89, ns), but PET/CT
      was more specific (0.89 vs. 0.79, ns). When labs and PET/CT data were combined, a
      positive result for either test was 89% sensitive and a positive result for both
      tests was 100% specific for predicting 12-month progression of disease. Kaplan
      Meier analysis showed significantly greater TTP for those with a negative vs.
      positive PET/CT (P = 0.0005), negative vs. positive labs (P < 0.0001), and both
      tests negative vs. both tests positive (P < 0.0001). CONCLUSIONS:   Combining
      PET/CT with laboratory data improves the accuracy of prediction of
      relapse/progression within 12 months compared with each test alone. Thus,
      integration of PET/CT into myeloma follow-up is recommended, and the impact of
      this approach on management should be explored.

PMID- 21198867
TI  - Evidence for a possible anatomical subsite-mediated effect of tobacco in oral
      potentially malignant disorders and carcinoma.
AB  - PURPOSE: To test the hypothesis that cigarette smokers develop oral potentially
      malignant disorders or carcinomas in preferential anatomical subsites. METHODS:
      The association of smoking habit with the presence of oral lesions in specific
      anatomical subsites was assessed in 123 patients using the odds ratio analysis.
      RESULTS: When compared to all the other subsites, the relative frequency of
      smokers with lesions was higher in the buccal mucosa and in the floor of the
      mouth (FOM) (P=0.002 and P=0.005), while it was lower in the tongue (P<0.0005).
      Smokers were about 7 years younger than non-smokers (P=0.008). CONCLUSIONS: The
      association of smoking and age suggests that smoking may contribute to generate a
      field of injury that leads to lesions in shorter periods than other causes. The
      stronger relationship of smoking with lesions in the buccal mucosa and FOM than
      in the tongue suggests that tissue characteristics mediate the effects of
      tobacco.

PMID- 21198868
TI  - The effectiveness of systemic eradication therapy against oral Helicobacter
      pylori.
AB  - BACKGROUND: Helicobacter pylori infection is associated with numerous
      gastroduodenal diseases. The oral cavity could be a potential extragastric
      reservoir for H. pylori, and oral H. pylori might cause gastric reinfection after
      the eradication therapy. The aim of the study was to evaluate the presence of H.
      pylori in oral cavity of patients with gastric H. pylori infection and to examine
      the effectiveness of the eradication therapy against H. pylori in stomach and in
      the oral cavity. METHODS: Fifty-six patients with chronic periodontitis and
      gastric H. pylori were enrolled in the study. Gastric H. pylori infection was
      determined using (13) C-urea breath test before and 3 months after eradication
      therapy. The presence of the oral H. pylori was assessed using polymerase chain
      reaction before and 3 months after eradication therapy. The 1-week eradication
      therapy consisted of amoxycilin 1 g, clarithromycin 500 mg, and proton pump
      inhibitor 20 mg twice a day. RESULTS: Of 56 subjects with gastric infection, 23
      (41.1%) harbored H. pylori in the oral cavity. Eradication rate in stomach was
      78.3%, whereas in the oral cavity, H. pylori was not detected from any sample
      after the eradication therapy. CONCLUSION: Almost half of the patients with
      gastric H. pylori harbored the bacterium in the oral cavity. After the
      eradication therapy, H. pylori was not detected in the oral cavity, what suggests
      high effectiveness of the therapy protocol in the oral cavity, or it is possible
      that oral H. pylori is of a transient character.

PMID- 21198869
TI  - Differential expression of perlecan receptors, alpha-dystroglycan and integrin
      beta1, before and after invasion of oral squamous cell carcinoma.
AB  - OBJECTIVES: The deposition of perlecan, a heparan sulfate proteoglycan, is
      enhanced within oral carcinoma in situ (CIS) foci, while it dynamically switches
      from CIS foci to the stromal space in squamous cell carcinoma (SCC). Because
      alpha-dystroglycan and integrin beta1 have been identified as two of the perlecan
      receptors, we wanted to determine their differential distributions before and
      after invasion of oral SCC. METHODS:  Eighty-two surgical tissue specimens of
      oral SCC containing different precancerous stages were examined by
      immunohistochemistry for perlecan, alpha-dystroglycan, integrin beta1, and Ki-67.
      In addition, alpha-dystroglycan mRNA signals were localized by in situ
      hybridization. RESULTS: In normal epithelia, alpha-dystroglycan and integrin
      beta1 were localized on the cell membrane of basal cells, while perlecan was
      faintly present in the intercellular spaces of parabasal cells. In epithelial
      dysplasia and CIS, alpha-dystroglycan and perlecan were well co-localized in the
      epithelial layer, especially in its lower half, and this co-localization was
      mostly overlapped with Ki-67-positive (+) cell zones. However, in SCC, alpha
      dystroglycan was localized neither within carcinoma cell nests nor in the stroma,
      while perlecan disappeared from SCC foci but emerged in the stromal space,
      leaving integrin beta1+ and Ki-67+ cells only to the periphery of SCC foci. alpha
      Dystroglycan mRNA signals were basically identical to the alpha-dystroglycan
      protein localizations. CONCLUSION: The findings suggest that alpha-dystroglycan
      and integrin beta1 act as perlecan receptors in oral precancerous lesions prior
      to invasion, and that the perlecan signals via the two different receptors
      function in cellular differentiation and proliferation of CIS cells,
      respectively.

PMID- 21198870
TI  - Lycopene: features and potential significance in the oral cancer and precancerous
      lesions.
AB  - Data from epidemiological studies have indicated that diets rich in fruits and
      vegetables are likely to benefit many aspects of the prevention of oral
      malignancy. Lycopene is a red-coloured carotenoid predominantly accumulated in
      tomatoes as well as other fruits and vegetables. It has been claimed to alleviate
      chronic diseases such as cancers and cardiovascular disease. Hence, the aim of
      this review is to summarize the features and its potential significance of
      lycopene in the development, prevention and treatment of oral premalignant
      lesions and oral cancer. Studies showed that lycopene might have beneficial
      effects in the management of some premalignant lesions in the oral cavity
      including oral submucous fibrosis and oral leukoplakia and may be an adjunct in
      the prevention and therapy of oral cancer. However, more mechanistic studies and
      randomized controlled trials of large sample size are necessary to further
      confirm these effects and to eventually make lycopene to be used in the community
      prevention and clinically routine management of these diseases.

PMID- 21198871
TI  - Immunoexpression of MMP-9, VEGF, and vWF in central and peripheral giant cell
      lesions of the jaws.
AB  - BACKGROUND: Central giant cell lesion (CGCL) and peripheral giant cell lesion
      (PGCL) are pathological conditions of the jaws that share the same microscopic
      features, but differ clinically in terms of their behavior. Our aim was to
      compare the immunoexpression of vascular endothelial growth factor (VEGF) and
      matrix metalloproteinase-9 (MMP-9) in CGCL and PGCL, relating them to the
      angiogenic index. METHODS: Twenty CGCL and 20 PGCL were selected for analysis of
      the immunoexpression of MMP-9 and VEGF in multinucleated giant cells (MGC) and
      mononucleated cells (MC). Angiogenic index was determined by microvessel count
      (MVC) using anti-von Willebrand factor antibody. RESULTS: The CGCL showed
      slightly higher expression of MMP-9 than PGCL. In comparison with PGCL, the CGCL
      showed higher expression of VEGF both in MC (P < 0.05) and in total cells (P <
      0.05). PGCL exhibited higher MVC than CGCL (P < 0.05). CONCLUSIONS: MMP-9 and
      VEGF might play an important role in the osteoclastogenesis process in CGCL. The
      higher MVC in PGCL might be related to the reactive nature of these lesions.

PMID- 21198872
TI  - Evaluation of myofibroblasts in oral submucous fibrosis: correlation with disease
      severity.
AB  - BACKGROUND: Oral submucous fibrosis (OSMF) is a chronic debilitating disease and
      a premalignant condition of the oral cavity characterized by generalized
      submucosal fibrosis. Myofibroblasts are contractile cells expressing alpha-smooth
      muscle actin (alpha-SMA) and are considered primary producers of extracellular
      matrix after injury. Their accumulation has been established as a marker of
      progressive fibrosis in organs like lungs, liver, kidney and skin. This study
      aims to evaluate the presence of myofibroblasts in various histological stages of
      OSMF. MATERIALS AND METHOD: Seventy cases of OSMF, which were further categorized
      histologically into early (35 cases) and advanced (35 cases), were subjected to
      immunohistochemistry using alpha-SMA antibody for detection of myofibroblasts.
      Fifteen normal oral mucosa specimens were also stained as controls. RESULTS: The
      number of alpha-SMA-stained myofibroblasts in OSMF was significantly increased
      when compared to that of the normal controls (P<0.001). Additionally, a
      statistically significant increase in the myofibroblasts population between early
      and advanced stages was observed (P=0.000). CONCLUSIONS: Our results corroborate
      the possibility that OSMF actually represents an abnormal healing process in
      response to chronic mechanical and chemical irritation because of areca nut
      chewing as demonstrated by the increased incidence of myofibroblasts in this
      disease. Furthermore, the progressive increase in myofibroblasts from early to
      advanced stages suggests their potential use as markers for evaluating the
      severity of OSMF.

PMID- 21198873
TI  - Mastocytosis: oral implications of a rare disease.
AB  - Mastocytosis encompasses a group of rare clinical entities, which are
      characterized by an abnormal growth and, usually, low accumulation of clonal and
      morphologically abnormal mast cells (MCs), within one or more organs. Clinical
      presentations are quite variable and symptoms are usually related to the release
      of mast cell mediators, tissue infiltration by MC (usually in the aggressive
      categories of the disease), or both. Mast cells are hematopoietic-derived cells
      that reach phenotypic maturity in the mucosa and peripheral connective tissues.
      These cells play an active role both on immunologic and non-immunologic
      processes. Within the oral cavity, MCs reside in the connective tissues, in
      physiologic conditions, and their number is elevated in pathologic situations
      resulting from immunoinflammatory processes, such as pulpal inflammation and
      periodontal disease. As MCs influence so many phenomena within the oral cavity,
      mastocytosis may manifest itself in the oral tissues. Patients with mastocytosis
      should be put under special care by dental professionals, in what concerns not
      only general patient management, but also drug prescription, as they are
      particularly prone to anaphylaxis and other peri and post-operative
      complications. Several allergens or mast cell activation triggers such as local
      anesthetics, zinc oxide, eugenol, penicilins, metals and oral hygiene products
      are frequently administered or prescribed by dentists. Patients with mastocytosis
      may also require stress management, during dental consultation. This review aims
      to briefly summarize the potential ways in which mast cell disease may affect the
      oral cavity and the dental management of mastocytosis affected patients.

PMID- 21198876
TI  - Photonanodermatology: the interface of photobiology, dermatology and
      nanotechnology.
AB  - This review focuses on the optical properties of matter on the nanoscale and
      discusses some of their potential applications in dermatology. The applications
      will be divided into three main categories: those with consumer potential; those
      with diagnostic potential; and those with therapeutic potential.

PMID- 21198874
TI  - Heat shock protein 47 expression in oral squamous cell carcinomas and upregulated
      by arecoline in human oral epithelial cells.
AB  - BACKGROUND: Heat shock protein 47 (HSP47) is a product of CBP2 gene located at
      chromosome 11q13.5, a region frequently amplified in human cancers. Areca quid
      chewing is a major risk factor of oral squamous cell carcinoma (OSCC). The aim of
      this study was to compare HSP47 expression in normal human oral epithelium and
      OSCC and further to explore the potential mechanisms that may lead to induce
      HSP47 expression. METHODS: Thirty-two OSCC specimens and ten normal oral tissue
      biopsy samples without areca quid chewing were analyzed by immunohistochemistry.
      The oral epithelial cell line OC2 cells were challenged with arecoline, a major
      areca nut alkaloid, by using Western blot analysis. Furthermore, glutathione
      precursor N-acetyl-l-cysteine (NAC), extracellular signal-regulated protein
      kinase (ERK) inhibitor PD98059, phosphatidylinositol 3-kinase (PI3K) inhibitor
      LY294002, cyclooxygenase-2 inhibitor NS-398, and tyrosine kinase inhibitor
      herbimycin A were added to find the possible regulatory mechanisms. RESULTS:
      HSP47 expression was significantly higher in OSCC specimens than normal
      epithelium (P<0.05). No significant difference in HSP47 expression was observed
      with respect to age, sex, T category, stage, and differentiation (P>0.05). The
      lower HSP47 expression was associated with lymph node metastasis (P=0.015).
      Arecoline was found to elevate HSP47 expression in a dose- and time-dependent
      manner (P<0.05). The addition of NAC, PD98059, LY294002, NS398, and herbimycin A
      markedly inhibited the arecoline-induced HSP47 expression (P<0.05). CONCLUSION:  
      Our findings demonstrated that HSP47 expression is significantly upregulated in
      areca quid chewing-associated OSCCs. HSP47 could be used clinically as a marker
      for lymph node metastasis of oral carcinogenesis. In addition, arecoline-induced
      HSP47 expression was downregulated by NAC, PD98059, LY294002, NS398, and
      herbimycin A.

PMID- 21198877
TI  - Photomedicine and phototherapy considerations for patients with skin of color.
AB  - BACKGROUND/PURPOSE: Patients with skin of color present unique challenges and
      opportunities for dermatologists in their disease states as well as their
      response to treatment. There are differences in dosing for patients with skin of
      color using standard phototherapeutic approaches as well as unique disease states
      that may respond to newer phototherapeutic options. Lastly, there are optical
      diagnostic options that allow investigators to differentiate erythema and
      pigmentation in a quantitative manner for clinical research purposes. METHODS:
      Review of the current literature with regard to vitiligo, hidradenitis
      suppurativa and optical diagnostic methods. CONCLUSIONS: Practitioners need to be
      aware of the various phototherapy and laser therapy options for patients with
      skin of color. New discoveries for the use of visible light as a form of
      treatment are on the horizon, and optical diagnostic techniques such as diffuse
      reflectance spectroscopy and colorimetry may add value clinically and within the
      research realm as objective measures of pigmentation and erythema.

PMID- 21198878
TI  - Efficacy and safety of hemoporfin in photodynamic therapy for port-wine stain: a
      multicenter and open-labeled phase IIa study.
AB  - BACKGROUND/PURPOSE: This phase IIa study aimed to study the efficacy and safety
      of hemoporfin in photodynamic therapy (PDT) with a 532 nm continuous laser for
      port-wine stain (PWS). METHODS: In this 8-week open-labeled study in three
      centers, three different laser exposure times (532 nm continuous laser for 20, 30
      and 40 min) were used in stage I, group A, stage II, group B and stage III, group
      C, respectively. Primary efficacy assessment was performed by an independent
      group of experts, who reviewed the standardized photos. Secondary efficacy
      assessment consisted of the subjective grading of the PWS fading by the
      investigators and the patients. Treatment reactions and adverse events (AE) were
      recorded separately. RESULTS: Forty patients were initially enrolled in the
      study, but stage III had to be cancelled eventually for the safety of the
      patients. Patients in groups A and B showed similar satisfactory results in
      efficacy assessments, the total 'response' rate being 80.0% and 94.7% in groups A
      and B, respectively. The AE rates were also similar in the two groups. Self
      limiting photosensitive dermatitis and hyperpigmentation were the most frequently
      observed AE. CONCLUSION: Hemoporfin-PDT is effective and safe for patients with
      PWS aged 16-50.

PMID- 21198879
TI  - The 308-nm excimer laser: a promising device for the treatment of childhood
      vitiligo.
AB  - BACKGROUND: Numerous modalities have been used to treat vitiligo in children. Up
      to now, phototherapy and topical corticosteroids are the most commonly used
      treatments for adult vitiligo but studies evaluating the efficacy of these
      treatments in the pediatric population remain insufficient. OBJECTIVE: This study
      was a retrospective review to evaluate the efficacy and safety of 308-nm excimer
      laser treatment in 30 childhood vitiligo patients. METHODS: Thirty vitiligo
      patients with 40 vitiligo patches were evaluated after the cessation of 308-nm
      excimer laser treatment. RESULTS: Seventeen patients (56.7%) with 20 patches
      (50%) achieved an acceptable degree (>50%) of repigmentation at the end of the
      treatment, with five patches (12.5%) showing >75% of repigmentation. The
      treatment response showed anatomical preferences, favoring the face, neck and
      trunk. However, the treatment response did not correlate to the cumulative dose
      or duration of treatment. Side effects occurred in nine patients, but were
      transient and minimal. CONCLUSION: The results of this study shows that the 308
      nm excimer laser can be an effective and promising device for the treatment of
      various vitiligo types, other than generalized, in childhood.

PMID- 21198880
TI  - Multi-laboratory validation of very high sun protection factor values.
AB  - BACKGROUND: High sun protection factor (SPF) sunscreens have multiple benefits
      but there has not been validation of the test method for determining SPF values
      higher than 50. This study addresses specifically the accuracy and
      reproducibility of the high SPF test. METHODS: Two high SPF formulations with a
      standard reference (SPF 15) were tested at four independent test facilities
      according to the 2007 FDA proposed amendments to the sunscreen monograph.
      Statistical analysis was performed to compare the SPF results within each lab as
      well as the SPF results between different labs. RESULTS: The test formulations
      have overall mean values of 90.5 and 70.7. There was no statistically significant
      difference between the labs for either formulation and all four labs were able to
      statistically differentiate these two levels of SPF values. The coefficients of
      variance (CV) for the high SPF formulations were comparable to those of the
      corresponding SPF 15 reference within each lab. CONCLUSIONS: The data show that
      SPF values above 50 and up to at least 90 can be measured by multiple
      laboratories with accuracy and reproducibility.

PMID- 21198881
TI  - Polymorphous light eruption and benign summer light eruption in Italy.
AB  - BACKGROUND/PURPOSE: Polymorphous light eruption (PLE) heterogeneity has been
      postulated, but the existence of benign summer light eruption (BSLE) is
      controversial. We studied the prevalence of the clinical patterns, criteria
      distinguishing BSLE from PLE, and diagnostic usefulness of phototest. METHODS:
      Five Italian Photodermatology Centres recruited retrospectively 346 patients with
      typical clinical history and/or presentation of PLE. Age, gender, skin type,
      family history and presence of atopy were considered. UVA and UVB MEDs and
      provocative phototests with UVA and UVB were obtained with a standardized
      procedure. Photopatch tests were applied according to the IRCDG rules. ANA were
      assessed by indirect immunofluorescence. RESULTS: Four criteria (predominance of
      women, shorter latency, uninvolvement of the face and absence of relapse during
      summer) identified BSLE in only 6.1% of cases. All had positive phototests,
      mostly with UVA. Uninvolvement of face, short latency and no seasonal relapses
      identified 11.7% patients, mostly with positive phototests to UVA. Short latency
      and no seasonal relapses in women identified 11.2% patients. Uninvolvement of
      face and no seasonal relapses in women identified 8.1% of patients. Uninvolvement
      of face and short latency in women identified 17.6% of patients. CONCLUSION:
      Criteria diagnosed BSLE in only a minority of patients, who were positive at
      phototesting, mostly with UVA.

PMID- 21198882
TI  - Reduction of skin-homing cytotoxic T cells (CD8+ -CLA+) in patients with
      vitiligo.
AB  - BACKGROUND: Vitiligo is a frequently acquired, hereditary disease, characterized
      by achromic macules due to the absence of melanocytes. In contrast with earlier
      studies, in which the main pathogenic role was attributed to anti-melanocyte
      antibodies, recent papers have emphasized a role for CD8(+) cytotoxic T
      lymphocytes in melanocyte destruction. Fifteen percent of peripheral T cell
      express cutaneous lymphocyte-associated antigen (CLA), responsible for skin
      homing T cell. Phototherapy is used to treat patients with generalized vitiligo
      and it has been shown to interfere with CLA(+) T cells in other skin diseases.
      OBJECTIVE: To describe peripheral blood T cell subpopulations' frequency and
      ability to express the skin-homing molecule (CLA) in patients with non-segmental
      vitiligo, before and after photochemotherapy (PUVA). PATIENTS AND METHODS: Twenty
      two patients with generalized and active spreading vitiligo were submitted to 30
      PUVA-8MOP sessions. Lymphocyte immunophenotyping was performed by flow cytometry
      using anti-CD3, anti-CD8 and anti-CLA monoclonal antibodies. Fifteen healthy
      volunteers, sex- and age-matched, were included as a control group. RESULTS:
      CD8(+) -CLA(+) T cells were significantly reduced in number in untreated vitiligo
      patients (P=0.008) when compared with control individuals, albeit with a more
      intense CLA expression (P=0.028). These findings were not altered after PUVA. No
      significant difference was noticed in CD4/CD8 ratios nor in CD4-CLA(+) T cell
      numbers between vitiligo patients and controls, both before and after PUVA.
      CONCLUSIONS: CD8-CLA(+) T cells are reduced in peripheral blood of patients with
      non-segmental vitiligo. This finding may be related to the previously reported
      increase of CD8(+) cells in both lesions and perilesional skin of these patients.

PMID- 21198883
TI  - Successful treatment of resistant alopecia areata with a phototoxic dose of
      ultraviolet A after topical 8-methoxypsoralen application.
AB  - BACKGROUND: The efficacy of a phototoxic dose of ultraviolet A (UVA) after
      topical application of 8-methoxypsoralen (8-MOP) in the treatment of alopecia
      areata (AA) was evaluated previously in only one study. However, the possibility
      of spontaneous regrowth of hair cannot be excluded as sessions were carried out
      every 3 months. OBJECTIVE: To determine the efficacy of a phototoxic dose of UVA
      after topical application of 8-MOP in the treatment of AA resistant to other
      lines of treatment. SUBJECTS/METHODS: Thirty-five patients with AA were treated
      by topical 8-MOP application to the lesions followed by UVA irradiation using a
      phototoxic dose every 3 months for a maximum of four sessions. Severity grading
      of AA was carried out using the Severity of Alopecia Tool (SALT) score before and
      after treatment. RESULTS: Fifty-seven percent of patients showed a positive
      treatment response (40% showed complete and 17% showed partial response) with
      significant improvement of SALT score. The mean cumulative UVA dose was 22+/-8.3
      J/cm(2). Mild reversible side effects were observed in 63% of patients after the
      first session. CONCLUSION: Phototoxic psoralen and ultraviolet A therapy after
      topical application of 0.1% 8-MOP is an effective treatment option for resistant
      AA, with low total cumulative UVA dose, few treatment sessions, and minimal
      reversible side effects.

PMID- 21198884
TI  - Herpes simplex virus reactivation as a complication of photodynamic therapy.
AB  - We report the case of an 81-year-old male patient who developed a reactivation of
      herpes simplex virus localized to the right forehead, where photodynamic therapy
      (PDT) for actinic keratosis was performed. Considering the wide use of PDT,
      herpes virus infection or reactivation as well as other infections seem to be a
      very rare but potentially serious complication that has to be distinguished from
      common inflammatory reactions after PDT. Further applications of PDT under
      antiviral prophylaxis were well tolerated by our patient, with no further
      herpetic reactivation and successful treatment of actinic keratoses.

PMID- 21198885
TI  - Solar urticaria unresponsive to intravenous immunoglobulins.
AB  - The treatment of solar urticaria (SU) can be difficult. Only a few cases of SU
      have been treated with intravenous immunoglobulins (IVIg) (as monotherapy or
      combined with phototherapy), with reported fast and durable increase of solar
      exposure tolerance. A 61-year-old female with severe UVB- and UVA-induced SU and
      a 62-year-old female with severe UVA and visible light-induced SU were both
      treated with a single course of IVIg (total dose of 2 g/kg), infused over 3 days.
      Phototest, performed 3 months after the treatment, showed only a slight minimal
      urticating dose improvement, and both patients reported just a moderate and
      'transient' subjective improvement. Our patient's poorer response, compared with
      previous reports, may be due to differences in IVIg's treatment schedules, which
      are reviewed.

PMID- 21198886
TI  - Ultraviolet A1 exposure is crucial in the treatment of prurigo nodulalis using a
      ultraviolet A1/topical steroid combination regimen.

PMID- 21198887
TI  - Thoron in indoor air: modeling for a better exposure estimate.
AB  - Only recently, the radioactive gas thoron ((220)Rn) and its decay products have
      been regarded as significant health risk in the indoor environment. This is
      because of new findings of increased thoron concentrations in traditional mud
      dwellings and considerations leading toward reduced action levels for natural
      airborne radionuclides. A model which describes the sources and sinks of thoron
      and its decay products should help to assess the indoor exposure. This work
      presents an extensive depiction of the influences of indoor conditions on the
      occurrence of these radionuclides. Measurements were performed in an experiment
      room and in mud dwellings in China and India. Mud even with an average (232)Th
      concentration was identified as a significant thoron source. The spatial
      distribution of the decay products proved to be homogeneous, which is in contrast
      to thoron gas. The prominent contribution of the unattached and attached decay
      product (212)Pb to the exposure was elaborated. The theoretically derived impact
      of air exchange and aerosol concentration, which determines the proportion of
      unattached decay products, could be confirmed. Transfer coefficients of the model
      were determined. The thoron model with these transfer coefficients predicts
      annual doses of almost 2 mSv for dwellers of traditional Chinese and Indian mud
      buildings, confirming the potential health impact of thoron. PRACTICAL
      IMPLICATIONS: The radioactive noble gas radon with its decay products is well
      known as a health risk. After increased concentrations of the isotope (220)Rn
      (thoron) have been found in traditional Chinese mud-walled cave dwellings, the
      need for a model that describes the occurrence of thoron and its decay products
      indoors has arisen. This work presents such a model from the emergence of thoron
      in the building material until the decay to the stable (208)Pb and discusses the
      various influences on the occurrence of these nuclides. The model makes possible
      to predict the exposure of people staying in a room to thoron and its decay
      products and--combined with a dose model--to calculate their inhalation doses
      from easily measurable data.

PMID- 21198888
TI  - Relationships between mite allergen levels, mold concentrations, and sick
      building syndrome symptoms in newly built dwellings in Japan.
AB  - This study investigated the possible relationships between exposures to mite
      allergen and airborne fungi with sick building syndrome (SBS) symptoms for
      residents living in newly built dwellings. We randomly sampled 5709 newly built
      dwellings in six prefectures from northern to southern Japan. A total of 1479
      residents in 425 households participated in the study by completing questionnaire
      surveys and agreeing to environmental monitoring for mite allergen (Der 1),
      airborne fungi, aldehydes, and volatile organic compounds. Stepwise logistic
      regression analyses adjusted for confounders were used to obtain odds ratios (OR)
      of mite allergen and fungi for SBS symptoms. Der 1 had a significantly high OR
      for nose symptoms. Rhodotorula had a significantly high OR for any symptoms, and
      Aspergillus had significantly high OR for eye symptoms. However, the total colony
      forming units had a significantly low OR for throat and respiratory symptoms.
      Eurotium had a significantly low OR for skin symptoms. In conclusion, dust-mite
      allergen levels and indoor airborne Rhodotorula and Aspergillus concentrations
      may result in SBS symptoms in newly built dwellings. PRACTICAL IMPLICATIONS:
      Various factors can cause sick building syndrome symptoms. This study focused on
      biologic factors such as dust-mite allergen and airborne fungi in newly built
      dwellings in Japan. Dust-mite allergen levels were significantly associated with
      higher rates of nose symptoms, airborne Rhodotorula concentrations were
      significantly associated with higher rates of any symptoms, and Aspergillus
      concentrations were significantly associated with higher rates of eye symptoms.
      Measures should be taken to reduce mite allergen levels and fungal concentrations
      in these dwellings.

PMID- 21198890
TI  - EAO 19th Annual Scientific Meeting Abstracts.

PMID- 21198889
TI  - Methodologies for quantifying culturable, viable, and total Legionella
      pneumophila in indoor air.
AB  - Legionella pneumophila, aerosolized from numerous indoor facilities (e.g., shower
      heads, hot tubs, spas), may cause Pontiac fever (PF) and lethal pneumonia named
      Legionnaires' disease (LD) in humans. Reliable methods on quantitative exposure
      assessment of this bioaerosol are essential for the prevention of PF and LD.
      Coupled with culture, ethidium monoazide with qPCR, and qPCR assays, the
      collection efficiency for culturable, viable, and total L. pneumophila was
      assessed by means of filtration sampling (IOM with gelatin filter and cassette
      with polycarbonate filter) and liquid-based sampling methods (BioSampler, AGI-30,
      MAS-100 sampler with Tween mixture and deionized water (DW)). Results show
      IOM/gelatin filter was comparable to cassette/polycarbonate filter (P = 0.33) and
      performed greater than all of tested liquid-based methods for total cell
      collection. On the other hand, IOM/gelatin filter obtained greater efficiencies
      than cassette/polycarbonate filter by a factor of 3.8-8.6 for viable cells (P =
      0.0006) and two orders of magnitude for culturable cells (P = 0.00002). Further
      comparison between liquid impingement and filtration methods indicates the
      sampling by IOM/gelatin filter, AGI-30, and BioSampler with DW were the most
      appropriate for viable cells, while culturable cells were collected most
      efficiently by BioSampler/DW with periodical replenishment during the sampling.
      PRACTICAL IMPLICATIONS: This study recommends the most suitable methodologies for
      quantifying culturable, viable, and total Legionella pneumophila in indoor air.
      By using appropriate sampling and analytical methods, the residents and building
      owners are able to obtain the reliable data and further characterize the exposure
      risk and/or intervention efficacy against L. pneumophila. Moreover, the adoption
      of suitable monitoring methods also assists the investigators to explore the
      sources linked to PF and LD during the outbreaks. Considering reliable microbial
      monitoring is fundamental for epidemiological survey and risk assessment, the
      present information should be taken into account in assessing L. pneumophila
      indoors.

PMID- 21198891
TI  - The effect of chemotherapeutic agents on contaminated titanium surfaces: a
      systematic review.
AB  - OBJECTIVE: To systematically collect and evaluate the existing evidence for the
      abilities of different chemotherapeutic agents to decontaminate biofilm
      contaminated titanium surfaces. MATERIAL AND METHODS: PubMed-MEDLINE and the
      Cochrane-CENTRAL databases were searched, covering research published on or
      before June 2010, to identify appropriate studies. The eligible studies were
      controlled studies on the effects of chemical treatments on biofilm-contaminated
      titanium surfaces. RESULTS: In total, 2425 unique papers were identified.
      Independent screening of the titles and abstracts resulted in only four
      publications that met all of the eligibility criteria. None of the in vivo
      studies assessed titanium surface decontamination in a controlled fashion. Three
      studies provided in vitro data, and one used an ex vivo protocol. Citric acid was
      found to be the most effective treatment in lipopolysaccharide removal as
      compared with an untreated control, although its effectiveness was equivalent to
      those of water and saline. In addition, citric acid demonstrated the greatest
      efficacy in cleaning the contaminated titanium surface, as evidenced by scanning
      electron microscopy. CONCLUSION: The data reported for the efficacy of
      chemotherapeutic agents in cleaning contaminated titanium surfaces are scarce,
      which precludes the generation of firm conclusions. Based on the lack of robust
      data, we cautiously conclude that citric acid is the chemotherapeutic agent with
      the highest potential for the removal of biofilms from contaminated titanium
      surfaces in vitro, although it does not achieve complete removal. To date, the
      killing effect of citric acid against biofilms has not been investigated on
      titanium surfaces.

PMID- 21198892
TI  - Experimental model of bone response to xenografts of bovine origin (Endobon): a
      radiological and histomorphometric study.
AB  - OBJECTIVE: To carry out a radiological and histomorphometric evaluation of bone
      response to bovine bone implants inserted in rabbits' tibiae. MATERIALS AND
      METHODS: Twenty New Zealand rabbits weighing 3900-4500 g were used. Twenty bovine
      bone implants (Endobon) in granulated form of 500-1000 MUm granulometry were
      inserted in the proximal metaphyseal area of the animals' right tibia and 20
      control areas were located in the proximal metaphyseal area. Following
      implantation, the animals were sacrificed in four groups of five, after 1 month,
      2 months, 3 months and 4 months, respectively. Anteroposterior and lateral
      radiographs were taken. Samples were sectioned at 5 MUm and stained using
      Hematoxylin-Eosin and Masson's trichromic. RESULTS: After 4 months, radiological
      images showed complete repair of the bone defects. No healed or residual bone
      alterations attributable to the presence of the implant were observed.
      Histomorphometric analysis at 4 months showed the presence of a higher density of
      newly formed bone with mean values for new bone, residual graft material and non
      mineralized connective tissue of 22.8 +/- 1.5%, 39.4 +/- 2.3% and 37.7 +/- 2.5%.
      There were no statistically significant differences in the length of cortical
      formation with bovine bone, 98.8 +/- 1.1%, compared with the control group, 99.1
      +/- 0.7%, at the end of the study period. CONCLUSIONS: The biomaterial used in
      the study was shown to be biocompatible, osteoconductive and non-resorbable and
      as such a possible bone substitute that does not interfere with normal reparative
      bone processes.

PMID- 21198893
TI  - Soft tissue development around abutments with a circular macro-groove in healed
      sites of partially edentulous posterior maxillae and mandibles: a clinical pilot
      study.
AB  - OBJECTIVES: The aim of this study was to evaluate soft tissue development at
      concave circular macro-grooved titanium abutments in healed sites. MATERIAL AND
      METHODS: In a split-mouth pilot study 10 patients received two implants each at
      healed posterior sites in contralateral maxillary or mandibular jaw quadrants.
      Either circular macro-grooved concave study abutments or conventional convex
      control abutments were immediately provisionalized and received permanent crowns
      3 months postimplantation. Marginal bone level, papilla index, modified plaque
      and bleeding index were recorded. The esthetic outcome was evaluated with
      standardized perpendicular pictures according to the Pink Esthetic Score (PES).
      Statistical analysis included the description of all variables by mean value,
      standard deviation and range. PES values were compared using the Wilcoxon signed
      rank test for paired data. RESULTS: Cumulative survival rate for all 20 implants
      was 100%. At the 1-year follow-up, there was no statistical significant
      difference of marginal bone levels between sites restored with the study (-0.11
      +/- 0.77 mm) vs. the control (-0.34 +/- 0.53 mm) abutments (P>0.05). Esthetic
      evaluation (PES) revealed statistically significant differences in scores between
      the study group [study abutment group] (7.2 +/- 2.82, 8 +/- 1.89) and the control
      group [control abutment group] (9.5 +/- 1.58, 10.5 +/- 1.72) at the time of
      prosthetic delivery and the 1-year follow-up. Whereas PES scores for mesial
      papilla at control sites at the 1-year follow-up demonstrated statistically
      significant higher values, both soft tissue level and soft tissue contour at
      control sites revealed statistically significantly higher PES values (P<0.05) at
      time of prosthetic delivery and at 1-year follow-up when compared with study
      sites. CONCLUSIONS: Concave macro-grooved abutments in healed posterior maxillary
      and mandibular sites did not exhibit a superior soft tissue development compared
      with standard convex abutments.

PMID- 21198894
TI  - Study of the osseointegration of dental implants placed with an adapted surgical
      technique.
AB  - OBJECTIVE: To study the osseointegration of dental implants placed with a
      modified surgical technique in Beagle dogs and to compare it with the
      conventional method. MATERIALS AND METHODS: Dental implants were placed
      bilaterally in the mandible of Beagle dogs using the press-fit as well as
      undersized implant bed preparation technique. Micro computer tomography (micro
      CT) and histometric methods were used to analyze the bone implant contact and
      bone volume (BV) around the implants. RESULTS: The bone-to-implant contact
      percentage (BIC: expressed as %), first BIC (1st BIC: expressed in mm), sulcus
      depth (SD: expressed in mm) and connective tissue thickness (CT: expressed in mm)
      were analyzed for both groups. The BIC percentage was significantly higher for
      the undersized installed implants (P=0.0118). Also, a significant difference
      existed between the undersized and press-fit installed implants for the first
      screw thread showing bone contact (P=0.0145). There were no significant
      differences in mucosal response (SD and CT) for both installation procedures.
      Also, no significant difference was found in the BV, as measured using micro-CT,
      between the implants placed with an undersized technique (59.3 +/- 4.6) compared
      with the press-fit implants (56.6 +/- 4.3). CONCLUSION: From the observations of
      the study, it can be concluded that an undersized implant bed can enhance the
      implant-bone response.

PMID- 21198895
TI  - Effects of a calcium phosphate coating on the osseointegration of endosseous
      implants in a rabbit model.
AB  - OBJECTIVES: The aim of the present study was to evaluate a Ca-P coated implant
      surface in a rabbit model. The Ca-P surface (test) was compared to the titanium
      porous oxide surface (control) in terms of bone-to-implant contact (BIC) and
      removal torque value. MATERIALS AND METHODS: Two hundred and sixteen dental
      implants were inserted in the tibia and in the femur of 36 rabbits. One hundred
      and eight were represented by Ca-P oxidized surface implant and other 108 were
      titanium porous oxide surface modified implants. Each rabbit received six
      implants. Animals were sacrificed after 2, 4 and 9 weeks of healing. Each group
      included 12 rabbits. The femoral implant and the proximal implant of the tibia of
      each animal were subjected to the histologic analysis and the distal implants of
      the tibia underwent removal torque test (RTQ). RESULTS: Histological analysis in
      terms of BIC and RTQ did not revealed any significant difference between the Ca-P
      oxidized surface and the oxidized surface at 2 and 4 weeks. At 9 weeks, the
      oxidized surface demonstrated better results in terms of RTQ in the tibia.
      CONCLUSION: In conclusion, findings from the present study suggested that the Ca
      P coating had no beneficial effect in improving bonding strength at the bone
      implant interface either at 2, 4 and 9 weeks.

PMID- 21198896
TI  - Early peri-implant tissue reactions on different titanium surface topographies.
AB  - OBJECTIVES: The purpose of the present study was to investigate the early peri
      implant soft tissue healing on different titanium surface topographies. MATERIAL
      AND METHODS: Titanium implants with smooth or rough surfaces were placed in the
      extraction site at 1 month after the maxillary first molar extractions of 15 male
      Sprague-Dawley rats. At 4 and 7 days after implant surgery, the peri-implant oral
      mucosa was randomly harvested and analyzed for collagen fiber orientation, and
      expression of extracellular matrix genes. Descriptive and paired t-tests were
      performed where appropriate (alpha = 0.05). RESULTS: The laser scanning
      microscopic analysis of the Sirius red stained peri-implant connective tissue
      revealed a parallel and uniform collagen fiber orientation along the smooth
      implant at both 4 and 7 days. In contrast, the collagen fibers of the comparative
      peri-implant tissue from rough surface implants at 7 days were not arranged in
      parallel orientation but in an irregular a "cotton-ball-like." The levels of mRNA
      of types III and XII collagen and transforming growth factor-beta1 significantly
      increased in the smooth implant group compared with the rough implant group at
      both 4 and 7 days or either one of days. CONCLUSION: The results of this study
      suggest that implant surface characteristics may affect early events of soft
      tissue healing by influencing collagen fiber orientation and expression of key
      genes for initial healing.

PMID- 21198897
TI  - Analysis of the pattern of the alveolar ridge remodelling following single tooth
      extraction.
AB  - INTRODUCTION: Tooth extraction is followed by marked osseous changes of the
      residual alveolar ridge including severe bone alterations both in height and in
      width. However, such remodelling could jeopardize the subsequent implant
      insertion for two main reasons. Firstly, the absence of adequate bone levels
      makes implant placement impossible; secondly, aesthetic problems in the
      fabrication of implanto-supported restoration could be caused by serious bone re
      absorption. Thus, it is of crucial importance that the dental surgeon knows how
      the alveolar crest changes when a single tooth has been removed. The aim of this
      study was to evaluate the pattern of alveolar crest remodelling observed in a
      single intercalated area of tooth extraction after at least a period of 6 months
      of healing, using standardized photos of model casts. MATERIAL AND METHODS: Among
      the patients who were treated for a single intercalated tooth extraction during
      the last 2 years at the department of dentistry at Versilia Hospital, Lido di
      Camaiore (Lucca), Italy, we selected 50 patients. The amount of alveolar crest
      remodelling was assessed on standardized photos of study models. All measurement
      were recorded on an Excel sheet (Excel, Windows XP((r))) and each value was
      multiplied by the enlargement index so that true values of re-absorption could be
      obtained. Finally, we have calculated the percentage of amount of alveolar crest
      remodelling and shifting of alveolar crest. RESULTS: We calculated the percentage
      of buccal remodelling and alveolar crest shift. The buccal re-absorption was 19.4
      +/- 9.4% at mesial point, 39.1 +/- 10.4% at midpoint and 20.3 +/- 10.7% at distal
      level. Moreover, the shift of the alveolar crest was 59.1 +/- 11.2% at mesial
      point, 64.8 +/- 10.5% at the midpoint and 56 +/- 12.5% at distal point.
      CONCLUSIONS: This study confirmed that buccal wall tends to re-absorb after the
      extraction according to a specific pattern. Thus, the re-absorption at the
      midpoint represent the double of bone loss at the distal and the mesial points.
      Furthermore, we have observed first how the alveolar crest shifts placing along
      the more lingual/palatal line which divides the original alveolar crest into
      three parts.

PMID- 21198898
TI  - Prevalence of periimplant disease in partially edentulous patients: a practice
      based cross-sectional study.
AB  - OBJECTIVES: Evaluation of the prevalence rates of periimplant mucositis and
      periimplantitis in partially edentulous patients in a private dental practice.
      MATERIAL AND METHODS: The data of 89 patients were collected (52 female, 37 male,
      age at time of implant placement: 51.8 +/- 10.3 years). All patients had been
      treated with dental implants of the same type and fixed superstructures between
      January 1999 and June 2006 (observational period: 68.2 +/- 24.8 months). RESULTS:
      The patient-related prevalence rate of periimplant mucositis (probing depth >= 4
      mm and bleeding on probing [BOP]) was over all 44.9%. The respective rates in non
      smokers without periodontal history were 30.4% and in smokers with periodontal
      history 80%. The multiple logistic regression analysis identified a significant
      association of mucositis with the independent variable "smoker" (odds ratio [OR]
      3.77; P = 0.023). The patient-related prevalence rate of periimplantitis (probing
      depth >= 5 mm, BOP/pus, radiographic bone loss) was 11.2% (smokers with
      periodontal history: 53.3%, non-smokers: 2.8%). No periimplant disease was
      diagnosed in non-smoking patients without periodontal history and with a good
      compliance after treatment. Statistical analysis identified a significant
      association of periimplantitis with "smoker" (OR: 31.58; P<0.001) and
      "compliance" (OR: 0.09; P = 0.011). Periodontal history in general showed no
      significant association with periimplantitis. CONCLUSIONS: Smoking and compliance
      are important risk factors for periimplant inflammations in partially edentulous
      patients.

PMID- 21198899
TI  - Preferences of dental care providers in maintaining compromised teeth in relation
      to their professional status: implants instead of periodontally involved
      maxillary molars?
AB  - AIM: The purpose of this study was to evaluate the dentists' decision making in
      the maxillary molar region to find out how it is influenced by general
      practitioners' and specialists' characteristics as well as by the external
      evidence. MATERIAL AND METHODS: A questionnaire was developed containing clinical
      cases and statements to assess practitioners' opinions on the treatment of
      periodontally involved maxillary molars and implant therapy with sinus grafting.
      Data were analysed with respect to the dentists' age and specialty. RESULTS:
      Three hundred and forty questionnaires were evaluated (24% from universities, 76%
      from educational courses, overall response rate 35.1%). Forty six per cent of all
      participants indicated they had specialised, 52% placed dental implants, while
      33% performed sinus grafting and 64% periodontal surgeries. Forty six per cent
      were against or were indecisive about having sinus grafting performed on
      themselves. The treatment proposals given for the clinical cases revealed a
      preference among older dentists and general practitioners for regenerative
      treatments even when these were not evidence based in through-and-through
      furcation involvements. Resective therapies were most often selected by
      periodontists. Prosthodontists tended to prefer more invasive treatment options
      with extractions and augmentations. More experienced general practitioners
      favoured conventional fixed dental prostheses in free-end situations or no
      treatment rather than the complicated augmentation procedures, which were
      preferred by younger dentists. CONCLUSIONS: Implant placement seems to be widely
      accepted by almost all subjects, who may either place implants themselves or
      refer patients. More information seems to be needed on the indications for
      regenerative therapies for furcation involved maxillary molars, and guidelines
      required for decision making in complex clinical situations.

PMID- 21198900
TI  - Variation in the total lengths of abutment/implant assemblies generated with a
      function of applied tightening torque in external and internal implant-abutment
      connection.
AB  - AIM: Settling (embedment relaxation), which is the main cause for screw
      loosening, is developed by microroughness between implant and abutment metal
      surface. The objective of this study was to evaluate and compare the relationship
      between the level of applied torque and the settling of abutments into implants
      in external and internal implant-abutment connection. MATERIAL AND METHODS: Five
      different implant-abutment connections were used (Ext, External butt joint + two
      piece abutment; Int-H2, Internal hexagon + two-piece abutment; Int-H1, Internal
      hexagon + one-piece abutment; Int-O2, Internal octagon + two-piece abutment; Int
      O1, Internal octagon + one-piece abutment). All abutments of each group were
      assembled and tightened with corresponding implants by a digital torque gauge.
      The total lengths of implant-abutment samples were measured at each torque (5,
      10, 30 N cm and repeated 30 N cm with 10-min interval) by an electronic digital
      micrometer. The settling values were calculated by changes between the total
      lengths of implant-abutment samples. RESULTS: All groups developed settling with
      repeated tightening. The Int-H2 group showed markedly higher settling for all
      instances of tightening torque and the Ext group was the lowest. Statistically
      significant differences were found in settling values between the groups and
      statistically significant increases were observed within each group at different
      tightening torques (P<0.05). After the second tightening of 30 N cm, repeated
      tightening showed almost constant settling values. CONCLUSIONS: Results from the
      present study suggested that to minimize the settling effect, abutment screws
      should be retightened at least twice at 30 N cm torque at a 10-min interval in
      all laboratory and clinical procedures.

PMID- 21198901
TI  - Stability, marginal bone loss and survival of standard and modified sand-blasted,
      acid-etched implants in bilateral edentulous spaces: a prospective 15-month
      evaluation.
AB  - OBJECTIVES: Chemical modification of the already proven sand-blasted and acid
      etched (SLA) implant had increased its surface wettability and consequent early
      term osseointegration characteristics. The aim of this clinical trial was to
      compare the stability changes, success, survival, peri-implant parameters and
      marginal bone loss (MBL) of the early-loaded standard (SLA) and modified sand
      blasted, acid-etched (modSLA) implants. MATERIAL AND METHODS: A total of 96 SLA
      and modSLA implants were placed in a bi-lateral, cross-arch position to the jaws
      of 22 patients. Resonance frequency analysis (RFA) was used to measure the
      implant stability in the surgery and following healing after 1, 3 and 6 weeks. At
      the stage of loading, a panoramic X-ray was obtained and RFA measurement was
      repeated for all implants. Implants were restored by metal-ceramic crowns and
      followed for 1 year to determine the success, survival rate, peri-implant
      parameters and MBL. Results were compared by one- and two-way ANOVA, log-rank
      test and generalized linear mixed models (P < 0.05). RESULTS: One modSLA implant
      was lost after 3 weeks following the surgery yielding to a 100 and 97.91% success
      rate for SLA and modSLA implants, respectively (P = 0.323). At the loading stage,
      modSLA implants showed significantly lower MBL (0.18 +/- 0.05 mm) than SLA
      implants (0.22 +/- 0.06 mm; P = 0.002). In the loading stage, RFA value of the
      modSLA implants (60.42 +/- 6.82) was significantly higher than the both implant
      types in the surgical stage (55.46 +/- 8.29 and 56.68 +/- 8.19), and following 1
      (56.08 +/- 7.01 and 55.60 +/- 9.07) and 3 weeks of healing (55.94 +/- 5.95 and
      55.40 +/- 6.50 for SLA and modSLA implants, respectively). CONCLUSIONS: modSLA
      implants demonstrated a better stability and a reduced MBL at the loading stage.
      Both SLA and modSLA implants demonstrated a favorable success and survival at the
      end of 15-month follow-up.

PMID- 21198902
TI  - Computer-aided design and manufacturing construction of a surgical template for
      craniofacial implant positioning to support a definitive nasal prosthesis.
AB  - AIM: To design a surgical template to guide the insertion of craniofacial
      implants for nasal prosthesis retention. MATERIALS AND METHODS: The planning of
      the implant position was obtained using software for virtual surgery; the
      positions were transferred to a free-form computer-aided design modeling software
      and used to design the surgical guides. A rapid prototyping system was used to 3D
      print a three-part template: a helmet to support the others, a starting guide to
      mark the skin before flap elevation, and a surgical guide for bone drilling. An
      accuracy evaluation between the planned and the placed final position of each
      implant was carried out by measuring the inclination of the axis of the implant
      (angular deviation) and the position of the apex of the implant (deviation at
      apex). RESULTS: The implant in the glabella differed in angulation by 7.78
      degrees , while the two implants in the premaxilla differed by 1.86 and 4.55
      degrees , respectively. The deviation values at the apex of the implants with
      respect to the planned position were 1.17 mm for the implant in the glabella and
      2.81 and 3.39 mm, respectively, for those implanted in the maxilla. CONCLUSIONS:
      The protocol presented in this article may represent a viable way to position
      craniofacial implants for supporting nasal prostheses.

PMID- 21198906
TI  - Influence of space-filling materials in subantral bone augmentation: blood clot
      vs. autogenous bone chips vs. bovine hydroxyapatite.
AB  - AIM: The first objective of the present study was to compare the short- and long
      term 3D volume stability of sub-sinusal bone regeneration in rabbits using
      different space fillers. The second objective was to assess qualitatively and
      quantitatively the early bone formation process and long-term behavior of the
      regenerated bone. MATERIALS AND METHODS: Fifteen rabbits underwent a double sinus
      lift procedure using: blood clot (Clot), autogenous bone chips (Auto) and bovine
      hydroxyapatite (BHA). Animals were euthanized at 1 week, 5 weeks and 6 months.
      Samples were subjected to X-ray microtomography and histology. Variations in the
      volume of bone augmentations were calculated at different time points.
      Qualitative analysis was performed using 7 MUm sections and quantitative
      histomorphometric analyses were carried out using scanning electron microscopy.
      RESULTS: From baseline (100%) to 5 weeks, the augmented volumes declined to 17.3%
      (Clot), 57.6% (Auto) and 90.6% (BHA). After 6 months, only 19.4% (Clot) and 31.4%
      (Auto) of initial volumes were found, while it remained more stable in the BHA
      group (84%). At 1 week, an initial osteogenesis process could be observed in the
      three groups along the bone walls. At 5 weeks, despite a significant decline in
      the volume, newly formed bone density was higher with Clot and Auto than with
      BHA. At 6 months, bone densities were statistically similar in the three groups.
      However, after 6 months, the surface invaded by newly formed bone (regenerated
      area) was significantly higher when BHA was used as space filler. In the BHA
      group, the biomaterial area slightly decreased from 42.7% (1 week) to 40% (5
      weeks) and 34.9% (6 months) and the density of the composite regenerated tissue
      (bone+BHA) reached >50% at 6 months. CONCLUSIONS AND CLINICAL IMPLICATIONS: The
      three space fillers allowed bone formation to occur. Nevertheless, augmented
      volumes declined in the Clot and Auto groups, while they remained stable with
      BHA. A slowly resorbable biomaterial might be suitable in sub-sinusal bone
      augmentation for preventing the re-expansion process and for augmenting the
      density of the regenerated tissues.

PMID- 21198905
TI  - Guided bone regeneration with a synthetic biodegradable membrane: a comparative
      study in dogs.
AB  - OBJECTIVES: The aim of the present study was to compare a newly developed
      biodegradable polylactide/polyglycolide/N-methyl-2-pyrrolidone (PLGA/NMP)
      membrane with a standard resorbable collagen membrane (RCM) in combination with
      and without the use of a bone substitute material (deproteinized bovine bone
      mineral [DBBM]) looking at the proposed tenting effect and bone regeneration.
      MATERIALS AND METHODS: In five adult German sheepdogs, the mandibular premolars
      P2, P3, P4, and the molar M1 were bilaterally extracted creating two bony defects
      on each site. A total of 20 dental implants were inserted and allocated to four
      different treatment modalities within each dog: PLGA/NMP membrane only (Test 1),
      PLGA/NMP membrane with DBBM (Test 2), RCM only (negative control), and RCM with
      DBBM (positive control). A histomorphometric analysis was performed 12 weeks
      after implantation. For statistical analysis, a Friedman test and subsequently a
      Wilcoxon signed ranks test were applied. RESULTS: In four out of five PLGA/NMP
      membrane-treated defects, the membranes had broken into pieces without the
      support of DBBM. This led to a worse outcome than in the RCM group. In
      combination with DBBM, both membranes revealed similar amounts of area of bone
      regeneration and bone-to-implant contact without significant differences. On the
      level of the third implant thread, the PLGA/NMP membrane induced more horizontal
      bone formation beyond the graft than the RCM. CONCLUSION: The newly developed
      PLGA/NMP membrane performs equally well as the RCM when applied in combination
      with DBBM. Without bone substitute material, the PLGA/NMP membrane performed
      worse than the RCM in challenging defects, and therefore, a combination with a
      bone substitute material is recommended.

PMID- 21198907
TI  - Adrenocorticotropic tumor cells transplanted into mouse embryos affect pancreatic
      histogenesis.
AB  - A wide range of individual differences exist in the total number of functional
      and structural units in each organ, such as beta cells in pancreatic islands, and
      these units are the basis of the organ's overall function, including its
      functional reserve. The endocrine environment may influence organ histogenesis,
      during which functional and structural units are formed and increase in number.
      We analyzed the effects of a continuous high level of adrenocorticotropic hormone
      (ACTH) and/or secondarily induced glucocorticoid on histogenesis of the pancreas
      in mouse embryos. Pituitary tumor-derived AtT20 cells, which secrete ACTH
      continuously, were injected subcutaneously into mouse embryos at embryonic day
      (E) 12.5, and the embryos were allowed to develop exo utero until E18.5 (AtT20
      group). E18.5 AtT20 group embryos with high ACTH levels (23.74 +/- 6.19 ng/mL vs
      control group, 0.48 +/- 0.40 ng/mL, P < 0.05) were examined for the effects on
      histogenesis of the pancreas. Using serial sections of the E18.5 pancreas, we
      stereologically measured the volumes, and counted total cell numbers and numbers
      of mitotic or pyknotic cells of the whole pancreas, endocrine and exocrine cells,
      and glucagon-immunopositive alpha cells and insulin-immunopositive beta cells in
      the endocrine part. Although the volumes of the whole pancreas and exocrine part
      did not change significantly, in the AtT20 group the endocrine part was
      significantly larger, with fewer pyknotic cells and lower ratios of alpha and
      beta cells than in the control group. These results suggest that the high level
      of ACTH and/or glucocorticoid affects histogenesis of the pancreas.

PMID- 21198909
TI  - Controversy on the management of anticoagulants and antiplatelet agents for
      scheduled endoscopy.
AB  - Guidelines on the management of anticoagulants and antiplatelet agents for
      endoscopy were established by Japan Gastroenterological Endoscopy Society (JGES)
      in 2005. However, the permeation of the JGES guideline is reported to possibly be
      low. One of the important causes of this problem is the confusing situation of
      gaps between the guidelines of various societies. Additionally, our ongoing
      investigation has revealed another important cause, which is the current daily
      clinical practice that cessation periods before endoscopy were determined by non
      gastroenterological specialists who might be unfamiliar with the JGES guidelines.
      Considering the low permeation of the guidelines for non-gastroenterological
      specialists prescribing these agents, we propose that close coordination between
      various specialists is mandatory to fill the gap between endoscopists and non
      gastroenterological specialists.

PMID- 21198910
TI  - Carbon dioxide submucosal injection cushion: an innovative technique in
      endoscopic submucosal dissection.
AB  - AIM: Endoscopic submucosal dissection (ESD) can successfully resect large lesions
      en bloc, but it requires a satisfactory submucosal (sm) injection agent for
      proper safety and efficacy. The aim of the present study was to evaluate the
      effectiveness of carbon dioxide (CO(2) ) as an ESD sm injection agent. METHODS:
      In vitro study using porcine stomachs compared CO(2) with normal saline (NS) and
      sodium hyaluronic acid (SHA) solution, both of which are currently used to
      provide long-lasting sm elevation during ESD. Histopathological examination
      assessed differences between CO(2) and NS sm cushions. ESD were then carried out
      in vivo in the stomach and rectum of a live pig using CO(2) sm injection.
      RESULTS: CO(2) sm elevation was significantly longer lasting than either NS or
      SHA (P<0.001). Histopathology revealed no mucosal layer tissue damage, and
      dissection of honeycomb-like fibrous connective tissue in the CO(2) sm cushion.
      Creating and maintaining a CO(2) sm cushion of sufficient elevation combined with
      partial physical dissection of the sm layer was achieved, followed by complete
      endoscopic dissection of the sm layer with all ESD, resulting in successful en
      bloc resections having a mean specimen size of 24.3mm within 15min. CONCLUSION:
      Safety and efficacy of CO(2) as a satisfactory sm injection agent during ESD was
      successfully demonstrated in these preliminary studies, warranting further
      investigation of this innovative technique.

PMID- 21198912
TI  - Capsule endoscopy for obscure gastrointestinal bleeding in the tropics: report
      from India.
AB  - BACKGROUND: Capsule endoscopy (CE) is useful in patients with obscure
      gastrointestinal bleeding (OGIB). Experience in CE in OGIB in the tropics is
      limited. METHODS: Eighty-six patients with OGIB were evaluated clinically and
      using CE (Given Imaging, Yoqneam, Israel) 89 times (twice in three patients)
      during a 64-month period. Images were downloaded and examined by a single
      investigator using software (Rapid Reader; Given Imaging, Yoqneam, Israel).
      Patients received specific treatment and were followed up. Intraoperative
      findings, response to specific treatment and outcome on follow up (10.3+/-14.1
      months) were considered to confirm CE findings. RESULTS: Of 86 patients (aged
      54.5+/-16.3 years, 63 males), 64 and 22 had OGIB-overt and OGIB-occult,
      respectively. Lesions were equally detected in OGIB-overt and OGIB-occult
      patients (48/64, 75% vs 18/22, 81.8%, P= ns). Lesions were detected in 64 of 86
      (74.4%) patients [vascular malformations with or without fresh bleeding in 24
      (37.5%), tumors in 12 (18.8%), strictures in 15 (23.4%), ulcers in five (7.8%),
      hookworm in five (7.8%), and more than one lesion in three patients (4.7%)].
      Endoscopic insertion of the capsule was required in four patients, and in six it
      was retained, although none developed intestinal obstruction (surgical removal in
      two). The sensitivity, specificity, positive and negative predictive values of CE
      to detect the lesion(s) were 92.9%, 68.2%, 84.8%, and 83.3%, respectively.
      CONCLUSION: CE is safe and is equally effective in detecting lesion(s) in occult
      and overt OGIB. Worm infestation and small bowel tuberculosis are unique and
      important causes of OGIB in the tropics.

PMID- 21198911
TI  - Discrimination between sclerosing cholangitis-associated autoimmune pancreatitis
      and primary sclerosing cholangitis, cancer using intraductal ultrasonography.
AB  - BACKGROUND AND AIM: Differentiation of sclerosing cholangitis-associated
      autoimmune pancreatitis (SC-AIP), primary sclerosing cholangitis (PSC) and cancer
      of the hilar part of the bile duct (CHB) has been challenging. The aim of the
      present study was to evaluate characteristic intraductal ultrasonography (IDUS)
      features that could be used to discriminate SC-AIP from PSC and CHB. METHODS: Six
      patients with SC-AIP, 10 patients with PSC and 12 patients with CHB were
      identified. We reviewed the following bile duct features observed using IDUS to
      determine their usefulness for differentiating SC-AIP from PSC and CHB: presence
      of symmetrical wall thickness, wall thickness, presence of homogeneous internal
      foci and presence of lateral mucosal lesions continuous to the hilar. RESULTS:
      IDUS results (SC-AIP, PSC, CHB) were as follows: wall thickness (mm), 3.7+/-0.9,
      2.6 +/-0.9, 2.8+/-0.0.6; presence of symmetrical wall thickness, 100% (6/6), 20%
      (2/10), 8.3% (1/12); presence of homogeneous internal foci, 100% (6/6), 10%
      (1/10), 8.3% (1/12); and presence of lateral mucosal lesions continuous to the
      hilar, 83.3% (5/6), 40%(4/10), 25% (3/12). Symmetrical wall thickness of the bile
      duct, homogeneous internal foci and lateral mucosal lesions continuous to the
      hilar were detected significantly more often among the patients with SC-PSC than
      among the patients with PSC or CHB (P<0.05). CONCLUSIONS: IDUS findings, such as
      symmetrical wall thickness, presence of homogeneous internal foci and presence of
      lateral mucosal lesions continuous to the hilar can facilitate the differential
      diagnosis of SC-AIP from PSC and CHB.

PMID- 21198914
TI  - Endoscopic submucosal dissection for submucosal invasive gastric cancer and
      curability criteria.
AB  - AIMS: The aims of the present study were to evaluate the feasibility of
      endoscopic submucosal dissection (ESD) as curative treatment for node-negative
      submucosal invasive early gastric cancer (EGC) and to consider further expansion
      of the curability criteria for submucosal invasive EGC. METHODS: A total of 977
      EGC in 855 patients treated by ESD were enrolled. They were divided into
      intramucosal cancer (M); minimally submucosal invasive cancer (<500um from the
      muscularis mucosa) (SM1); and deeper submucosal invasive cancer (>500um from the
      muscularis mucosa) (SM2). The technical feasibility of ESD for SM1 and M were
      compared, and the clinical prognosis of SM1 was evaluated. Furthermore, the
      volume of carcinoma invading to the submucosal layer, which we called the SM
      volume index, was calculated virtually to analyze its correlation with lymphatic
      vascular invasion. RESULTS: There were no statistical differences in technical
      outcomes and complications between M and SM1. Curative resection rates were
      significantly better in M than in SM1 (M, 92.6%; SM1, 63.8%). No local
      recurrences and distant metastases were found in 48 SM1 patients declared to have
      undergone curative resections. Most cases (72.0%) with successful ESD but non
      curative resection exceeded 30mm in maximum size, and no local recurrences and
      metastases were found in these patients. The SM volume index of these cases was
      comparatively small. CONCLUSION: The technical and theoretical validity of ESD
      for SM1 was validated. The possibility of further expansion of the curability
      criteria for submucosal invasive cancers was suggested by the evaluation of the
      SM volume index.

PMID- 21198913
TI  - Endoscopic submucosal dissection using a grasping-type scissors forceps for early
      gastric cancers and adenomas.
AB  - AIM: To reduce the risk of complications related to endoscopic submucosal
      dissection (ESD) using knives, we developed a new grasping-type scissors forceps
      (GSF) that can grasp and incise the target tissue using electrosurgical current.
      The aim of the present study was to evaluate the efficacy and safety of ESD using
      GSF for the removal of early gastric cancers and adenomas. METHODS: ESD using GSF
      was carried out on 35 consecutive patients with early gastric cancers or adenomas
      who had preoperative EUS diagnoses of mucosal tumor without lymph node
      involvement. Therapeutic efficacy and safety were assessed. RESULTS: All lesions
      were treated easily and safely without unexpected incision. The mean size of
      epithelial tumors and resected specimens was 15.6mm and 32.7mm, respectively.
      Curative en-bloc resection rates according to tumor size and location were 96%
      (26/27) in tumors <=20mm, 100% (8/8) in tumors >20mm, 100% (18/18) of tumors in
      the lower portion, 100% (8/8) of tumors in the middle portion, 89% (8/9) of
      tumors in the upper portion, and 97% (34/35) overall. The mean operating time
      according to tumor size and location was 93.4min in tumors <=20mm, 140min in
      tumors >20mm, 77.6min for tumors in the lower portion, 113.4min for tumors in the
      middle portion, 148.6min for tumors in the upper portion, and 104.1min overall.
      No intraoperative complication occurred, and postoperative bleeding was seen in
      3% (1/35). CONCLUSIONS: ESD using GSF allows simple and safe en-bloc resection of
      early gastric cancer or adenoma irrespective of tumor size and location.

PMID- 21198915
TI  - Magnifying endoscopic findings of the surface structure of non-cancerous mucosa
      surrounding differentiated and undifferentiated gastric carcinoma.
AB  - BACKGROUND: Several reports have described the usefulness of magnifying endoscopy
      in observing the surface structure in gastric neoplasia. The aim of the present
      study was to evaluate the characteristics of the surface structure of non
      cancerous mucosa surrounding gastric cancer. METHODS: Sixty Japanese patients
      with early gastric cancer were enrolled in this study. We observed the non
      cancerous gastric mucosa surrounding gastric carcinoma by magnifying endoscopy
      and classified the magnified view into four patterns: (A) dotted; (B) short
      linear; (C) striped; and (D) granular, according to Sakaki's classification.
      RESULTS: All patients were diagnosed as having Helicobacter pylori infection, and
      histological evaluation revealed 46 types of differentiated and 14 types of
      undifferentiated-type gastric carcinomas. There were significant differences in
      the gender, age and endoscopic-atrophic-border scale between patients with these
      two types. In all, the surface structure at 240 points (4 points each in 60
      patients) of non-cancerous mucosa was observed by magnifying endoscopy. The
      prevalences of the surface patterns of the mucosa surrounding differentiated
      carcinoma were: A, 1.1%; B, 8.1%; C, 28.3%; D, 62.5%, and those of the mucosa
      surrounding undifferentiated carcinoma were: A, 8.9%; B, 73.2%; C, 14.3%; D,
      3.6%. There were significant differences in the surface structure of the non
      cancerous mucosa surrounding differentiated and undifferentiated gastric
      carcinoma. CONCLUSION: The microsurface structure of the gastric mucosa
      surrounding gastric cancer lesions differed between patients with differentiated
      and undifferentiated gastric cancer. These findings are expected to be useful for
      the early detection of gastric carcinoma lesions or for the determination of
      extensions of carcinoma lesions.

PMID- 21198916
TI  - Unilateral versus bilateral drainage using self-expandable metallic stent for
      unresectable hilar biliary obstruction.
AB  - BACKGROUND: There is no consensus on the choice of either unilateral or bilateral
      drainage in stent placement for patients with unresectable hilar biliary
      obstruction. The aim of the present study was to clarify which drainage method is
      superior. METHODS: We retrospectively reviewed 82 patients with hilar biliary
      obstruction who underwent metallic stenting. These patients were divided into a
      unilateral drainage group (Uni group) and a bilateral drainage group (Bi group).
      RESULTS: There was no significant difference between the groups in median
      survival time, median stent patency period, and median complication-free survival
      time. The most frequent complication was stent obstruction, followed by
      cholangitis. Liver abscess was found at a higher frequency in the Bi group
      (17.6%) than in the Uni group (1.5%) (P=0.0266). There was no significant
      difference between the groups in the occurrence of two or more complications
      (P=0.247), life-threatening severe complications (P=0.0577), and stent
      obstruction by sludge (P=0.0912). CONCLUSION: When compared with bilateral
      biliary drainage, unilateral biliary drainage is associated with a lower
      incidence of liver abscess as well as a comparable outcome of stent patency time
      and complication-free survival. We therefore propose that hilar biliary
      obstruction can be treated first by unilateral drainage with a metallic stent and
      by bilateral drainage only in patients who develop cholangitis in the
      contralateral biliary tree.

PMID- 21198917
TI  - New method of covered wallstents for distal malignant biliary obstruction to
      reduce early stent-related complications based on characteristics.
AB  - AIM: We previously reported a low occlusion rate with covered Wallstents for
      malignant biliary obstruction, but stent-related complications other than
      occlusion posed a problem. A modified covered Wallstent insertion method based on
      stent characteristics was evaluated to reduce stent-related complications.
      METHODS: A total of 138 patients with distal malignant biliary obstruction
      received covered Wallstent placement. From October 2001 to October 2003, 69
      patients received covered Wallstent placement (Group 1). Thereafter, we modified
      our stent insertion method and 69 patients received stent placement using this
      modified method from November 2003 to January 2007 (Group 2). The modified
      insertion method consists of endoscopic sphincterotomy carried out in patients
      without pancreatic duct invasion and longer stent placement with the center of
      the stent located in the center of the biliary stricture to prevent pancreatitis,
      kinking of the bile duct, and stent dislocation. A comparative analysis was
      carried out using prospectively collected data in these two cohorts. RESULTS:
      Tumor ingrowth was not observed, and stent occlusion rate was 18.8% in Group 1
      and 23.2% in Group 2. The overall rates of stent-related complications did not
      differ (39.1% in Group 1 and 30.4% in Group 2), but stent-related complications
      within 3months decreased from 22 episodes in Group 1 to 13 episodes in Group 2.
      Median event-free survival was prolonged by modified stent insertion method
      (125days in Group 1 and 268days in Group 2, P=0.020), although cumulative
      survival and stent patency were not significantly different. CONCLUSIONS: Our
      modified method of covered Wallstent placement showed improved event-free
      survival.

PMID- 21198918
TI  - Quantitative analysis of low-dose aspirin-associated small bowel injury using a
      capsule endoscopy scoring index.
AB  - AIM: The major limitation of capsule endoscopy (CE) has been the lack of a
      standardized and validated severity scale for mucosal injury. The aim of the
      present study was to verify the usefulness of quantifying small bowel mucosal
      changes associated with giving low-dose aspirin (LDA) using a CE scoring index.
      METHODS: The CE score for small bowel mucosal injury was investigated to evaluate
      the severity of mucosal injury. Healthy volunteers and patients suspected of
      having small bowel disease were recruited for this study. The short-term LDA
      group (V+S-LDA group) consisted of volunteers who took low-dose aspirin for
      14days; this group was then compared with healthy volunteers who did not receive
      LDA treatment (V-Control group). The long-term LDA group (L-LDA group) consisted
      of patients with at least a 3-month history of daily LDA use; this group was
      compared with non-users of LDA (P-Control group). RESULTS: The CE score was
      significantly higher in the V+S-LDA group than in the V-Control group. In the V
      Control group, almost all the subjects were categorized as exhibiting a 'normal'
      change. 'Mild' changes were observed significantly more frequently in the V + S
      LDA group than in the V-Control group. The CE score was significantly higher in
      the L-LDA group than in the P-Control group. 'Mild' or 'moderate or severe'
      changes were observed significantly more frequently in the L-LDA group than in
      the P-Control group. CONCLUSION: The CE scoring system was useful for evaluating
      LDA-associated small bowel mucosal disease activity and for objectively scoring
      the small bowel inflammatory disease state.

PMID- 21198919
TI  - Lateral spread along the main pancreatic duct in branch-duct intraductal
      papillary-mucinous neoplasms of the pancreas: usefulness of intraductal
      ultrasonography for its evaluation.
AB  - BACKGROUND: Intraductal papillary mucinous neoplasms (IPMN) of the pancreas tend
      to spread intraepithelially along the pancreatic duct wall. We evaluated
      histopathological intraductal lateral spread (LS) along the main pancreatic duct
      (MPD) from branch-duct IPMN and investigated the usefulness of intraductal
      ultrasonography (IDUS) for its preoperative diagnosis. PATIENTS AND METHODS:
      Twenty-four patients with branch-duct IPMN who had undergone preoperative IDUS
      and surgery were reviewed clinicopathologically. The prevalence and histological
      length of LS along the MPD from branch-duct IPMN, characteristics of the patients
      with LS, and efficacy of LS assessment by IDUS were examined. RESULTS: LS along
      the MPD was observed in 54% of the subjects. In the group of patients with LS,
      its mean length was 25.2+/-16.8mm (5-50mm) and the diameter of the MPD was 6mm or
      greater. Of the patients with LS, those in whom the length of LS along the MPD
      was longer than the diameter of the cystically dilated branch accounted for 30%.
      The diameter of the MPD in the group with LS was significantly greater than that
      in the group without LS (P=0.03). The sensitivity, specificity, and overall
      accuracy of IDUS in the detection of LS were 92%, 91%, and 92%, respectively.
      CONCLUSION: LS along the MPD was detected in about half of the resected cases of
      branch-duct IPMN. Preoperative transpapillary IDUS may be beneficial for the
      determination of the resection line, especially in those branch-duct IPMN
      patients in whom the MPD is 6 mm or greater in diameter.

PMID- 21198920
TI  - Low-frequency of bacteremia after endoscopic submucosal dissection of the
      stomach.
AB  - BACKGROUND: Mainstream therapy for early gastric cancer in Japan has now shifted
      from endoscopic mucosal resection (EMR) to endoscopic submucosal dissection
      (ESD). Although bacteremia is reported as being infrequent and transient in
      gastric EMR, there are no reports of it being investigated in gastric ESD. This
      study aimed to determine the frequency of bacteremia in gastric ESD. PATIENTS AND
      METHODS: A prospective study, in 46 consecutive patients who underwent gastric
      ESD, investigated the frequency of bacteremia before and after the procedure.
      RESULTS:   The median time for the total ESD procedure was 105min (range 30-400).
      The median volume of the submucosal injection was 80ml (range 20-260). The mean
      size of the resected specimen was 40+/-9.7mm. Blood cultures obtained before ESD
      were positive in 4.4% (2/45) of cases. Bacillus subtilis and Bacillus spp. were
      the isolated microorganisms. Blood cultures obtained 10min after ESD were
      positive in 4.3% (2/46) of cases; with the same microorganisms being isolated.
      Blood cultures obtained 3h after ESD were all negative. No signs of sepsis were
      seen in the two patients with a positive blood culture 10min after ESD.
      CONCLUSIONS: The frequency of bacteremia after gastric ESD was low and transient.
      ESD for gastric lesions is thought to have a low risk of infectious
      complications; therefore, prophylactic administration of antibiotics may not be
      warranted.

PMID- 21198921
TI  - Short-term outcomes of endoscopic submucosal dissection (ESD) for early gastric
      neoplasm: multicenter survey by osaka university ESD study group.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) was developed for en bloc
      removal of large and flat gastrointestinal tract neoplasms. In Japan, ESD is
      performed under conscious sedation. The risks for sedation-related complications
      of ESD, such as postoperative pneumonia, have not been evaluated. The aim of this
      study was to evaluate the incidence of postoperative pneumonia after ESD in a
      multicenter survey. PATIENTS AND METHODS: A total of 1188 patients with upper
      gastric neoplasms treated with ESD in nine hospitals were enrolled from May 2003
      to September 2008. The en bloc resection rates and complications (bleeding,
      perforation, and postoperative pneumonia) were assessed. The correlations between
      the clinical variables and complications were investigated using logistic
      regression models. RESULTS: The en bloc resection rate was 95.3%. Bleeding,
      perforation, and pneumonia occurred in 37 (3.1%), 49 (4.1%), and 19 (1.6%)
      patients, respectively. Univariate analysis indicated that procedure time, but
      not specimen size, or patient age, or sex, was significantly related to bleeding
      and perforation. The incidence of pneumonia was higher in patients with
      ulceration, older patients (>=75years), and those with a long procedure duration
      (>=5h). CONCLUSION: The incidence of pneumonia, but not perforation and bleeding,
      after ESD, is high in older patients (>=75years). Special care should be taken
      with older patients undergoing ESD to minimize the risk of postoperative
      pneumonia.

PMID- 21198922
TI  - Cardiovascular tolerance and autonomic nervous responses in unsedated upper
      gastrointestinal small-caliber endoscopy: a comparison between transnasal and
      peroral procedures with newly developed mouthpiece.
AB  - BACKGROUND: Transnasal esophagogastroduodenoscopy (EGD) with small-caliber
      endoscopy appears to be less stressful to the cardiovascular system and has good
      patient tolerance. ENDO LEADER, a newly developed mouthpiece for peroral EGD with
      small-caliber endoscopy, is expected to reduce patient stress. We compared the
      patient acceptance, cardiovascular tolerance and autonomic nervous responses
      between transnasal EGD and peroral EGD with ENDO LEADER. PATIENTS AND METHODS: A
      total of 130 patients (transnasal group, 77; peroral group, 53) were enrolled.
      Pulse rate (P), blood pressure (BP), and peripheral blood oxygen saturation
      (SpO(2) ) were monitored. Acceptance of EGD was also assessed. Autonomic nervous
      responses were evaluated through analysis of heart rate variability using
      amplitude of the high-frequency component (HF) and low-frequency-to-high
      frequency power ratio (LF/HF) as indices of cardiac vagal activity and
      sympathetic activity, respectively. RESULTS: Analysis of patient acceptance
      showed no differences between the two groups, except with regard to nasal pain.
      Increases in BP and P between before and during EGD examination were
      significantly higher in the peroral group. Although throat pain and overall
      tolerance scores were significantly correlated with DeltaBP and DeltaP, no
      correlations with nasal pain score were noted. Heart rate variability analysis
      revealed that heart rate increased significantly in the peroral group, but there
      were no differences in DeltaHF or DeltaLF/HF between the two groups. CONCLUSIONS:
      Patient acceptance was not significantly different between the transnasal and
      peroral with ENDO LEADER groups; however, transnasal EGD appears to be less
      stressful to the sympathetic nervous system, leading to smaller elevations in BP,
      P and heart rate.

PMID- 21198923
TI  - Analysis of plastic stents in the treatment of large common bile duct stones in
      45 patients.
AB  - BACKGROUND: Although endoscopic plastic biliary stenting is a clinical procedure
      routinely carried out in patients with common bile duct stones, the effects of
      stenting on the sizes or fragmentation of large common bile duct stones have not
      been formally established and the mechanism of this condition is controversial.
      We compared the stone sizes of common bile duct stones after biliary stenting in
      order to develop the mechanism. PATIENTS AND METHODS: Endoscopic plastic biliary
      stenting was performed in 45 patients with large common bile duct stones or those
      difficult to extract with conventional endoscopic therapy, including mechanical
      lithotripsy. The stone diameter was >=16mm in all patients. Bile duct drainage
      and endoscopic placement of 7-8.5 Fr plastic biliary stents were established in
      all patients. Differences of stone sizes and fragmentations after biliary
      stenting were compared. The complete stone clearance rate after treatment was
      obtained. RESULTS: After biliary stenting for 3-6months, the bile stones
      disappeared or changed to sludge in 10 (10/45) patients, and fragmentation of the
      stones or decreased stone sizes were seen in 33 patients, whose stone median size
      was significantly decreased from 23.1mm to 15.4mm in 33 patients (P<0.05). The
      stones were removed successfully with basket, balloon, mechanical lithotripsy or
      a combination in 43 (43/45) patients. The remaining two patients (2/45)
      demonstrated no significant changes in stone sizes. CONCLUSION:   Plastic biliary
      stenting may fragment common bile duct stones and decrease stone sizes. This is
      an effective and feasible method to clear large or difficult common bile duct
      stones.

PMID- 21198924
TI  - Single-session endoscopic bilateral y-configured placement of metal stents for
      hilar malignant biliary obstruction.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy and safety of
      endoscopic bilateral biliary metal stent placement for hilar malignant
      obstruction. PATIENTS AND METHODS: Twenty patients with unresectable malignant
      hilar biliary obstruction who had undergone endoscopic bilateral Y-configured
      biliary drainage with metal stents were enrolled as a study group (YMS group).
      Thirty-seven patients who had undergone bilateral drainage with plastic stents
      were selected as a historical control (PS group). Two newly designed metal stents
      for bilateral Y-configured placement were endoscopically deployed in a partial
      stent-in-stent manner in one session. Technical success, early complications, and
      stent patency were evaluated. RESULTS: The technical success rate in the YMS
      group was 100%. Mild post-endoscopic retrograde cholangiopancreatography
      pancreatitis occurred in one patient in the YMS group and in two in the PS group.
      The success rate of biliary decompression was 95% in the YMS group and 89% in the
      PS group (P=0.65). During a median follow-up period of 7.3months, the incidence
      of stent occlusion in the YMS group was significantly lower than that in the PS
      group (30% vs 62%, P=0.028). Mean stent patency in the YMS group was 250days and
      that in the PS group was 115days (P=0.0061). Risk factors for stent occlusion
      were bile duct cancer (P=0.035) and the PS group (P=0.07) by multivariate
      analysis. CONCLUSION: Single-session endoscopic bilateral biliary placement of
      newly designed metal stents for hilar malignant obstruction is safe and useful
      with a high technical success rate and a long patency period.

PMID- 21198925
TI  - Transient unilateral vocal cord paralysis during endoscopic ultrasound.

PMID- 21198926
TI  - Experimental laparoscopic evaluation of double balloon versus spiral enteroscopy
      in an animal model.

PMID- 21198927
TI  - Hemolytic episode following an upper gastrointestinal endoscopy in a patient with
      paroxysmal nocturnal hemoglobinuria.

PMID- 21198928
TI  - Abdominal pain and ascariasis.

PMID- 21198929
TI  - Congenital duodenal diaphragm.

PMID- 21198930
TI  - Trans-jejunal endoscopic management of abdominal abscesses following total
      gastrectomy.

PMID- 21198931
TI  - Abstracts of the 10th Asian Congress of Urology of the Urological Association of
      Asia. Taipei, Taiwan. August 27-31, 2010.

PMID- 21198936
TI  - Editorial Comment to Prognostic impact of preoperative serum CYFRA 21-1 in
      patients with upper urinary tract urothelial carcinoma.

PMID- 21198937
TI  - Editorial Comment from Dr Shiraishi to Nationwide survey to evaluate the
      prevalence of varicoceles in South Korean middle school boys: a population based
      study.

PMID- 21198938
TI  - Editorial Comment from Dr Zampieri to Nationwide survey to evaluate the
      prevalence of varicoceles in South Korean middle school boys: a population based
      study.

PMID- 21198940
TI  - Late-onset incontinence in a cohort of radical prostatectomy patients.
AB  - A cohort of 235 subjects, who underwent radical prostatectomy from 1994 to 2002,
      completely continent at the 2-year follow up and with the last follow-up visit in
      2009, was examined to assess incidence and risk factors of late-onset
      incontinence. Median follow up was 100 months, range 84-176. At the last follow
      up visit, 209 (89%) maintained continence, and 26 (11%) became incontinent.
      Specifically 14 out of 26 (6%) used one pad and 12 (5%) used two or more pads
      daily. Incidence of age >= 65 years at radical prostatectomy was greater in the
      subgroup who developed late incontinence, 109/209 (52%) vs 19/26 (73%). Incidence
      of adjuvant or salvage radiotherapy, of hormonal manipulation and of
      extraprostatic disease was similar in the two subgroups. Univariate and
      multivariate analysis did not disclose any difference. Late-onset incontinence is
      to be expected in about 10% of subjects who became completely continent after
      radical prostatectomy. The cause is likely to be related to ageing. Patients
      should be informed about the long-term risk of becoming incontinent.

PMID- 21198939
TI  - Relationship between prostate-specific antigen and obesity in prostate cancer
      screening: analysis of a large cohort in Japan.
AB  - Previous studies have shown that lower prostate-specific antigen (PSA) levels in
      obese men might decrease the sensitivity of prostate cancer screening, leading to
      delayed diagnosis and unfavorable prognosis. We examined whether the effect of
      obesity is important in prostate cancer screening of Japanese men, who have a low
      prevalence of obesity. We analyzed 19,294 male subjects from a large cohort of
      Toyota Motor Corporation (TMC) employees (aged > 50 years, serum PSA level <= 4.0
      ng/mL) who underwent physical examinations from August 2006 to December 2009. The
      relationship between PSA level and obesity-related factors was analyzed by simple
      and multiple regression analysis. The relationships between six body mass index
      (BMI) categories, and PSA level and PSA mass (PSA concentration * plasma volume)
      were analyzed. PSA level decreased significantly with increasing BMI, but the
      coefficient of determination was very low. Mean PSA values decreased from 1.02 to
      0.85 ng/mL as BMI increased from underweight (BMI <18.5) to morbidly obese (BMI
      >35). However, PSA mass peaked in the overweight category and was slightly
      reduced with increasing BMI. On multiple regression analysis, PSA level was
      influenced by age, diastolic blood pressure and high-density lipoprotein as well
      as BMI. We found an inverse but weak relationship between PSA level and BMI.
      Obesity seems to have very limited influence on prostate cancer screening in this
      population. Nonetheless, when considering indications for prostatic biopsy in
      obese men, we should be aware that the hemodilution effect might reduce PSA
      levels.

PMID- 21198941
TI  - Positioning the instillation of contrast at the ureteral orifice cystography can
      be useful to predict postoperative contralateral reflux in children with
      unilateral vesicoureteral reflux.
AB  - The aim of the present study was to evaluate the usefulness of positioning the
      instillation of contrast at the ureteral orifice (PIC) cystography in prediction
      of postoperative contralateral reflux in patients with unilateral vesicoureteral
      reflux (VUR) undergoing ureteral reimplantation. Between January 2007 and March
      2009, 34 children (20 boys and 14 girls) had antireflux surgery for unilateral
      primary VUR. This was diagnosed by conventional fluoroscopic voiding
      cystourethrography (VCUG) in all patients. After induction of general anesthesia,
      PIC cystography was carried out immediately before ureteral reimplantation by
      instilling contrast material at the ureteral orifice. Patients with positive PIC
      cystogram on the contralateral side underwent bilateral ureteral reimplantation
      via the Cohen technique. VCUG was repeated at 6-12 months postoperatively. Of the
      34 patients, 16 (47%) showed VUR on the contralateral side on PIC cystography and
      underwent bilateral reimplantation. The remaining 18 patients (53%) with negative
      PIC cystogram underwent unilateral reimplantation, and no VUR was detected by
      postoperative VCUG in all ureters. None of the 34 patients had surgical
      complications or recurrent urinary tract infections. In conclusion, PIC
      cystography represents a useful tool to predict new onset contralateral VUR in
      patients with unilateral VUR on conventional VCUG.

PMID- 21198942
TI  - Asian School of Urology, Young Leaders' Workshop, Kyoto 2010.
AB  - PREFACE: As part of the 20th Anniversary Celebration of the Urological
      Association of Asia (UAA), the Asian School of Urology, Young Leaders' Workshop
      was held in Kyoto, 23-25 April 2010. The workshop focused on future national
      Asian leaders in the field of Urology and was arranged by the Asian School of
      Urology (ASU), an educational branch of the UAA, and Dr Osamu Ogawa, the workshop
      Organizer. Urologists from several Japanese universities contributed to the
      workshop as advisors, taskforce members, and group members. The workshop was also
      actively supported by Dr Allen Chiu (Taiwan) and Dr Stephen Lim (Singapore). A
      younger generation of urologists was invited to attend the workshop and, in all,
      29 delegates from 17 countries (Australia, Bangladesh, Cambodia, China, India,
      Indonesia, Iran, Korea, Malaysia, Myanmar, Nepal, Philippines, Singapore, Sri
      Lanka, Taiwan, Thailand, and Vietnam), chosen on the basis of recommendations
      from local councils, attended. The purpose of the workshop was to open channels
      of communication between future Asian leaders in Urology. The workshop topic was
      "Asian Clinical Guidelines". Workshop participants were divided into five groups
      addressing distinct issues associated with the notion of clinical guidelines:
      Group A, General Problems; Group B, Prostate Cancer; Group C, Stone Disease;
      Group D, Infectious Diseases; and Group E, Bladder Cancer. The workshop consisted
      of an introductory session, followed by three main sessions, each of which
      consisted of a group discussion of specific problems associated with the
      establishment of Asian Guidelines for Urological Diseases and how best to deal
      with them, followed by a plenary presentation of the outcomes.

PMID- 21198943
TI  - Retroperitoneal laparoscopic anatrophic nephrolithotomy for large staghorn
      calculi.
AB  - OBJECTIVES: Treatment of staghorn calculus is challenging. We evaluated the
      feasibility and efficacy of the retroperitoneal laparoscopic approach for the
      management of large staghorn renal calculi. METHODS: Patients with staghorn renal
      calculi unsuitable for percutaneous nephrolithotomy were analyzed. They underwent
      retroperitoneal laparoscopic anatrophic nephrolithotomy, involving control of the
      renal artery, stone removal through a nephrotomy incision on the Brodel's line
      and closure with continuous sutures. RESULTS: A total of 11 patients with renal
      stones were included in the present study. Mean patient age was 55 years (range
      42-68) and stone size was 52 mm (range 43-61). Warm ischemia time and operative
      duration were 31 (range 23-38) and 139 min (range 105-160), respectively. No
      blood transfusion was needed during or after operation. An 8-mm residual calculus
      remained in the lower calyces in one patient who was successfully treated by
      using shock wave lithotripsy. Intravenous pyelogram after surgery showed a
      functional corresponding renal unit, with an improvement in obstruction in all
      patients. CONCLUSIONS: Retroperitoneal laparoscopic technique can be applied for
      patients who are candidates for anatrophic nephrolithotomy. Larger studies with a
      longer follow up are needed to confirm these findings.

PMID- 21198944
TI  - When should we expect no residual tumor (pT0) once we submit incidental T1a-b
      prostate cancers to radical prostatectomy?
AB  - OBJECTIVES: To date, no tool exists to predict pT0 at radical prostatectomy (RP)
      in patients with T1a-T1b prostate cancer (PCa) after surgery for benign prostatic
      hyperplasia (SxBPH). We aimed to fill this gap by developing a user-friendly
      flowchart to assist urologists when incidental PCa is diagnosed and a clinical
      decision is required. METHODS: We analyzed 158 T1a-T1b prostate cancers patients
      who underwent RP between 1996 and 2009. A risk stratification tool was developed
      applying the tree modeling technique of classification and regression tree
      analysis (CART) and relying on all the available pre-RP characteristics (age,
      prostate-specific antigen [PSA] before SxBPH, PSA after SxBPH, cT1a-T1b stage,
      prostate volume and Gleason sum at SxBPH). Then, the accuracy of the proposed
      model using 200 bootstrap resamples for internal validation was calculated.
      RESULTS: A total of 95 patients (60.1%) were stage T1a, and 63 (39.9%) were stage
      T1b. The median values of PSA before and after SxBPH were 4.2 and 1.1 ng/mL,
      respectively. A total of 22 patients (13.9%) showed no residual tumor (pT0) at
      RP. The CART analyses identified three groups at risk of having residual disease
      at RP: (i) PSA after SxBPH > 1.0 ng/mL (pT0 prevalence: 3.8%); (ii) PSA after
      SxBPH < 1.0 ng/mL and PSA before SxBPH > 2.0 ng/mL (pT0 prevalence: 14.8%); and
      (iii) PSA after SxBPH < 1.0 ng/mL and PSA before SxBPH < 2.0 ng/mL (pT0
      prevalence: 42.3%). The accuracy of the proposed model was 77.1%. Clinical stage
      (T1a vs T1b) was not associated with pT0 (P = 0.4). CONCLUSIONS: Clinical stage
      (T1a vs T1b) assessment does not help in predicting pT0 cases. An accurate and
      clinically useful flowchart to predict pT0 at RP after incidental prostate cancer
      diagnosis is provided herein.

PMID- 21198945
TI  - Risk factors for overactive bladder in the elderly population: a community-based
      study with face-to-face interview.
AB  - OBJECTIVES: The aim of this study was to measure the prevalence of and risk
      factors for overactive bladder (OAB) in the elderly. METHODS: A cross-sectional
      study of elderly subjects was conducted by analyzing data from a community-based
      Comprehensive Geriatric Assessment on people aged 70 years or older. Trained
      interviewers performed face-to-face interviews for the assessment of urological
      symptoms. OAB definition was based on urgency and eight or more episodes of
      urination per day. The subjects completed a self-administered questionnaire
      including lifestyle evaluation, Geriatric Depression Scale, Mini-Mental Status
      Examination and medical history. Brachial-ankle pulse wave velocity was recorded
      to assess atherosclerotic disease. The analysis included 833 subjects, after the
      exclusion of 115 subjects who provided insufficient information. RESULTS: Based
      on the definition of OAB, 153 subjects (18.4%) were identified as having OAB.
      Univariate analysis showed a significant association between OAB and depressive
      symptoms. Multivariate analysis showed that the risk of having OAB was
      significantly higher in subjects with depressive symptoms, current drinkers, and
      overweight subjects with odds ratios of 2.37 (1.60-3.52, 95% confidence
      interval), 1.65 (1.04-2.62), and 1.51 (1.02-2.24), respectively. CONCLUSIONS:
      This is the first report to show an association between OAB and depressive
      symptoms and alcohol intake in an epidemiological study of elderly people. The
      reasons for these correlations remain unclear, but should be the foci of future
      OAB studies.

PMID- 21198946
TI  - Assessment and management of methotrexate hepatotoxicity in psoriasis patients:
      report from a consensus conference to evaluate current practice and identify key
      questions toward optimizing methotrexate use in the clinic.
AB  - Experts in psoriasis, hepatology, pharmacokinetics and pharmacogenetics convened
      to discuss the safety and monitoring of methotrexate with respect to
      hepatotoxicity when used in the treatment of psoriasis. Methotrexate is an
      efficacious and cost-effective treatment for psoriasis, but is associated with
      significant safety issues, particularly relating to hepatotoxicity. Current
      British, Dutch, German, EU and US guidelines for baseline evaluations, monitoring
      and prevention of hepatotoxicity in patients with psoriasis receiving
      methotrexate were evaluated. Liver safety monitoring is currently reliant upon
      multiple methods, including biopsy, serological tests for biomarkers such as type
      III procollagen amino terminal propeptide (PIIINP), and liver function tests
      based on liver enzymes. Monitoring of patients receiving long-term therapy is
      expected to be improved by the utilization of serum biomarkers currently in
      development such as the Enhanced Liver Fibrosis (ELF) panel and other non
      invasive tests of hepatic architecture, such as fibroelastography, microbubbles
      and magnetic resonance imaging. Appropriate studies to determine optimal dosing
      to maximize efficacy and minimize toxicity, potentially utilizing pharmacogenetic
      principles, are clearly needed. Key questions for future research are identified
      including needs for optimal screening and monitoring, identification of
      appropriate biomarkers, assessment of relationships between dosing and safety,
      utility of liver biopsy, optimal dosing regimens (including route of
      administration), methods to measure methotrexate levels in blood, and use of
      methotrexate as a standardized active comparator in trials of experimental drugs
      used to treat psoriasis.

PMID- 21198947
TI  - Low-cumulative dose isotretinoin treatment in mild-to-moderate acne: efficacy in
      achieving stable remission.
AB  - BACKGROUND: Aimed at the reduction of post-treatment relapse of severe acne, the
      cumulative dose of oral isotretinoin should be >=120 mg/kg. However, data on the
      appropriate oral isotretinoin treatment regimen in mild and moderate acne are
      lacking. OBJECTIVE: The purpose of this study was to determine the efficacy of an
      isotretinoin-sparing protocol in inducing permanent remission of mild and
      moderate acne. METHODS: In this open, prospective, non-comparative study, 150
      patients affected with mild-to-moderate acne were treated with isotretinoin until
      complete recovery and for a further month of treatment, independent of the total
      cumulative dose reached. Patients then underwent a 1-year maintenance therapy
      with adapalene 0.1% cream. Patients were followed up for a further year, without
      any treatment. RESULTS: A total of 139 patients completed the study. Overall,
      patients received a mean of 80.92 mg/kg cumulative dose of isotretinoin. In the 2
      year follow-up, relapse only appeared in 13 patients (9.35%). CONCLUSION:
      Comparing our findings with published data, this isotretinoin-sparing regimen was
      shown to be effective in inducing stable remission and preventing acne relapses
      in patients with mild-to-moderate acne. Low-cumulative dose regimens may
      potentially lead to a lower incidence of side-effects and to lower costs than
      higher doses.

PMID- 21198948
TI  - Stevens-Johnson syndrome and toxic epidermal necrolysis in children: a review of
      the experience with paediatric patients in a university hospital.
AB  - BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
      are life-threatening drug reactions considered to be part of the spectrum of a
      single pathological process. OBJECTIVE: To describe the clinical and
      epidemiological characteristics of SJS/TEN in children attended at our hospital.
      MATERIALS AND METHODS: Retrospective study of children diagnosed with SJS/TEN
      between 1999 and 2009 in a University Hospital provided with regional-level burn
      and paediatric intensive care units. RESULTS: We found 14 paediatric patients
      (eight SJS and six TEN). They presented an average of 60% of the body surface
      area affected and 31% of epidermal sloughing. The average of suspected drugs was
      1.7 per patient, anticonvulsants (carbamazepine, phenytoin and lamotrigine) and
      antibiotics (penicillin and macrolides) being the most frequent ones. Silver
      sulfadiazine was the topical treatment most frequently used, 86% of patients
      received systemic steroids and 28.5% intravenous immunoglobulins. One patient
      died. CONCLUSIONS: The SJS/TEN complex is a true dermatological critical
      condition that also affects children. Any drug can be the causative agent, more
      frequently anticonvulsants and antibiotics. Depending on the extension of the
      affected body surface, patients should be rapidly admitted to a critical care
      area with experience in the care of burn patients. Discontinuation of the
      suspected offending drugs is mandatory. Optimal supportive care and management of
      denuded skin areas are still the mainstay of treatment. The use of specific
      therapies remains controversial. Compared with adults, the disease in children
      seems to be milder with lower mortality.

PMID- 21198949
TI  - Acne-associated syndromes: models for better understanding of acne pathogenesis.
AB  - Acne, one of the most common skin disorders, is also a cardinal component of many
      systemic diseases or syndromes. Their association illustrates the nature of these
      diseases and is indicative of the pathogenesis of acne. Congenital adrenal
      hyperplasia (CAH) and seborrhoea-acne-hirsutism-androgenetic alopecia (SAHA)
      syndrome highlight the role of androgen steroids, while polycystic ovary (PCO)
      and hyperandrogenism-insulin resistance-acanthosis nigricans (HAIR-AN) syndromes
      indicate insulin resistance in acne. Apert syndrome with increased fibroblast
      growth factor receptor 2 (FGFR2) signalling results in follicular
      hyperkeratinization and sebaceous gland hypertrophy in acne. Synovitis-acne
      pustulosis-hyperostosis-osteitis (SAPHO) and pyogenic arthritis-pyoderma
      gangrenosum-acne (PAPA) syndromes highlight the attributes of inflammation to
      acne formation. Advances in the understanding of the manifestation and molecular
      mechanisms of these syndromes will help to clarify acne pathogenesis and develop
      novel therapeutic modalities.

PMID- 21198950
TI  - Nail psoriasis: a retrospective study on the effectiveness of systemic treatments
      (classical and biological therapy).
AB  - BACKGROUND: Nail psoriasis represents a challenge for specialists. There is no
      comparative study of systemic treatment's effectiveness at this site. OBJECTIVE:
      Evaluate the response of nail psoriasis to classical and biological therapy and
      to compare the effectiveness and safety of the different treatments. METHODS: We
      performed a retrospective study of 84 patients with moderate-severe psoriasis
      seen at our Department between January 2006 and January 2009. RESULTS: Psoriasis
      was severe in 53.4%. In 75% of cases, the fingernails were affected, and the
      mixed form was the most frequently subtype. The mean baseline scores on the PASI
      and the NAPSI were 23.12 and 14.7 respectively; the correlation between the two
      scores fell at weeks 12 and 24 but had risen again at week 48. The baseline NAPSI
      score tended to be lower in women and significantly higher in patients over 65
      years of age, family history of psoriasis, severe psoriasis and nail matrix
      involvement. In our series, 58.3% received classical treatment (acitretin,
      methotrexate, cyclosporin, PUVA, NUVB, REPUVA, RENUVB) and 41.7% received
      biological treatment (infliximab, efalizumab, etanercept, adalimumab).Significant
      reductions were found (P < 0.05) in the mean NAPSI scores at 12, 24 and 48 weeks
      with all the antipsoriatic agents except NUVB; significantly greater with
      cyclosporine (P < 0.01) and biological as infliximab and adalimumab at 12 and 24
      weeks (differences between treatments disappeared at 48 weeks). CONCLUSION: The
      response to treatment is slower in the nail lesions than in the skin lesions. The
      improvement of nail psoriasis is significant both with the classical treatments
      significantly higher in cyclosporin; and biological treatment (infliximab and
      adalimumab at 12 and 24 weeks).

PMID- 21198951
TI  - Pemphigus vegetans: a clinical, histological, immunopathological and prognostic
      study.
AB  - BACKGROUND: Pemphigus vegetans (P Veg) is a rare clinical form of pemphigus.
      Studies on P Veg are rare in the literature and none has so far evaluated the
      prognostic parameters. OBJECTIVE: In this retrospective study of P Veg, we aimed
      to analyse epidemiological, clinical, immunopathological and therapeutic data.
      Study of prognostic factors with accuracy of patient survival was also carried
      out. METHODS: This is a retrospective study (1981-2009) including 17 cases of P
      Veg. Statistical analysis was performed with chi-square and Fisher tests looking
      for a possible relationship between clinical data and prognostic factors. Follow
      up time and disease-free survival time were estimated using Kaplan-Meier methods.
      Clinical data were evaluated in univariate analysis looking for a significant
      association with survival. Equality of survival distribution was studied using
      log rank test. RESULTS: The hospital prevalence of P Veg was 0.0840/00 with a
      frequency of 9.1% among pemphigus. The mean age at onset was 47.6 years, with a
      sex-ratio (F/M) about 4.66. Neumann P Veg was the predominant clinical form
      (11/17). Clinically, the lesions were multifocal (16/17), prevailed on folds and
      mucous membranes. Under corticosteroids the mean period for healing was 24 +/- 9
      days. During the follow-up time, three patients died and 11 patients relapsed.
      Median of overall relapse-free survival was 13 +/- 1.7 months. No significant
      association between clinical data and prognostic factors was found. LIMITATIONS:
      This study was a retrospective chart analysis and the number of patients was
      small. CONCLUSION: The P Veg seems to be more frequent in Tunisia with high rate
      of mortality.

PMID- 21198952
TI  - Cognitive training with photographs as a new concept in an education campaign for
      self-detection of melanoma: a pilot study in the community.
AB  - BACKGROUND: Cognitive education using only photographs has been shown to be more
      effective than the ABCD algorithm to improve melanoma recognition in the general
      population. OBJECTIVE: The aim of this study was to assess the feasibility and
      acceptability of a campaign based on cognitive education by photographs instead
      of the usual ABCD algorithm. METHODS: Brochures including a panel of photographs
      of melanoma and moles were mailed, supported by a media campaign and followed by
      a telephone survey of a representative sample of the district population.
      RESULTS: Among the 855 people interviewed, 38% recalled the campaign and 13% had
      actually read the brochures. Among the 13%, 99% found them useful, 52% reassuring
      and 40% anxiety provoking, while 92% agreed that using images of skin cancer was
      the best way to recognize melanoma. Sixty-four percent declared that this
      campaign had prompted them to examine their own moles, 39% were prompted to check
      moles of family members, and only 11% would immediately visit a doctor.
      CONCLUSION: This pilot study shows that a melanoma campaign based exclusively on
      images is well accepted in the community, and is associated with a favourable
      impact on self-surveillance, while limiting overflow of unjustified
      consultations. We recommend this innovative concept be applied to large scale
      campaigns.

PMID- 21198953
TI  - Repigmentation of hair after latanoprost therapy.

PMID- 21198955
TI  - The correct meaning of the term 'immunocompromised': a necessary explanation.

PMID- 21198954
TI  - Advantages of preoperative hybrid SPECT/CT in detection of sentinel lymph nodes
      in cutaneous head and neck malignancies.
AB  - BACKGROUND: There is some controversy around the value of sentinel lymph node
      excision (SLNE). Especially SLNE of cutaneous head and neck malignancies has been
      debated intensively, in part because of the complexity of the lymphatic drainage
      in this region associated with potential high morbidity. In order to improve
      preoperative three-dimensional mapping of sentinel lymph nodes (SLN), in the head
      and neck region, by means of hybrid single photon emission computed
      tomography/computed tomography (SPECT/CT) is gaining significance. Our study
      seeks to identify the potential medical and economic advantages of preoperative
      SPECT/CT in direct comparison to standard SLNE without SPECT/CT in patients with
      cutaneous head and neck malignancies. METHODS: We retrospectively analysed the
      data of 48 clinically lymph node-negative patients with early stage melanoma,
      high risk cutaneous squamous cell carcinoma and porocarcinoma, who underwent SLNE
      with or without preoperative SPECT/CT within 4 years. RESULTS: The SLNE in the
      head and neck region with SPECT/CT-technique demonstrated better postoperative
      aesthetic results had lower morbidity and significantly reduced operating time.
      Moreover, SLNE with SPECT/CT-technique in the head and neck region was feasible
      using local anaesthesia (LA) and significantly reduced resulting costs
      (?32.65/SLNE with LA vs. ?334.57/SLNE with general anaesthesia, P < 0.0001).
      CONCLUSION: SPECT/CT is an innovative imaging technique, reliably and readily
      providing additional anatomical/functional information to detect and to excise
      SLN in the head and neck region. Therefore, SLNE with SPECT/CT-technique is an
      attractive option to improve the detection of SLN in cutaneous head and neck
      malignancies.

PMID- 21198956
TI  - Effect of method and time of first colostrum feeding on serum immunoglobulin
      concentration, health status and body weight gain in mithun (Bos frontalis)
      calves.
AB  - The effect of method and time of first colostrum feeding on the concentration of
      serum immunoglobulin (Ig) was evaluated in mithun (Bos frontalis) calves. The
      hypotheses were that the variable method and time of first colostrum feeding
      might affect the level of serum Ig and in turn the growth performance and health
      status of the claves during the early age. The newborn calves were randomly
      allotted to one of the four experimental groups - G-1: allowed to suckle the dam
      at own choice, G-2: separated immediately after birth and allowed to suckle the
      dam first at 6 h and then at own choice, G-3: bottle fed ad libitum colostrum of
      its own dam first at 6 h and then at 6-h intervals until 24 h, G-4: bottle fed ad
      libitum colostrum of its own dam within 1 h, at 6 h and then at 6-h intervals
      until 24 h. The concentrations of IgG, IgM, and IgA were lowest (p < 0.01) at
      birth and increased following colostrum feeding irrespective of the experimental
      group. Highest concentrations of all the Ig classes were observed at 12-24 h
      after birth. The concentrations then transiently decreased from day 7 to 14, and
      then steadily increased after day 28. The concentrations of IgG (p < 0.01) and
      IgA (p < 0.05) were higher in G-1 in relation to the other groups during the
      first week after birth. Similarly, higher concentration of IgA (p < 0.05) was
      found in G-1 in relation to the other groups during the rest of the experimental
      period. The apparent absorption efficiency of colostral IgG was higher (p < 0.05)
      in G-4 in relation to G-3. Growth rate and health status were not influenced by
      the method and time of first colostrum feeding. In conclusion, a 6-h delay in the
      first colostrum feeding reduced the level of serum Ig noticeably.

PMID- 21198957
TI  - The effects of increasing water content to reduce the energy density of the diet
      on body mass changes following caloric restriction in domestic cats.
AB  - Caloric restriction induces body mass loss that is often regained when
      restriction ends. This study aimed to determine if dietary energy density
      modulates the extent of post-restriction body mass regain. Water (20% wt:wt) was
      added to a standard dry commercially available feline diet. Twenty-seven domestic
      short-haired cats underwent a 20% caloric restriction on this diet. Following
      restriction, cats were offered the same dry diet ad libitum either without
      additional water or with 40% added water, therefore maintaining macronutrient
      composition whilst manipulating energy density. Despite no significant difference
      in energy intake during ad libitum consumption, post-restriction body mass regain
      was greater on the high energy dense (0% hydrated), compared to the low energy
      dense (40% hydrated) diet. The same protocol was repeated with a separate cohort
      of 19 cats with additional measures of physical activity, gut transit time and
      energy digestibility. Activity levels on the low energy dense diet were
      significantly higher than in cats on the high energy dense diet (p=0.030) and
      were similar to those recorded during caloric restriction. These results suggest
      that body mass gain following caloric restriction is ameliorated, and physical
      activity enhanced, by feeding a diet which is low in energy density due to the
      addition of 40% water.

PMID- 21198958
TI  - Utilization of milk amino acids by the suckling Iberian piglet.
AB  - Sixteen pure-bred Iberian (IB) sows were used in two trials to determine the
      efficiency of utilization of milk protein and amino acid (AA) for growth in
      suckling piglets. It was hypothesized that there may be one or more strongly
      limiting essential AA (EAA) responsible for the slow rate of growth of the IB
      piglet. This AA will show the highest fractional retention. Daily milk yield and
      composition were determined weekly over a 34-day lactation period. Within each
      litter, one piglet at birth and four piglets on d 35 of life were slaughtered.
      The protein content of the IB sow milk was similar to that reported for
      conventional breeds. However, branched-chain AA, Thr, Pro, Asp and Ala were in
      concentrations somewhat below the range of literature values and Arg and Met,
      substantially above it. Milk intake per piglet tended to be greater in Trial 2
      (832 vs. 893 g/day respectively; p = 0.066). However, the IB piglets grew at 168
      +/- 3.3 g/day, irrespective of the trial. The whole-body protein of piglets at
      weaning and the protein deposited in their body during the lactating period
      showed very close AA pattern. Among EAA, His and Arg show the highest fractional
      retentions (g AA retained/g AA ingested) in whole-body tissues (1.019 +/- 0.025
      and 0.913 +/- 0.017 respectively) and also the highest body to milk ratios (1.50
      and 1.41 respectively). Gly and Ala presented, among non essential AA, the
      highest efficiencies of utilization for tissue deposition (1.803 +/- 0.057 and
      1.375 +/- 0.026 respectively) and body to milk ratios (2.75 and 2.12
      respectively). These results suggest that the low efficiency of utilization of
      milk protein and the low rate of gain of the IB suckling piglet can be explained
      by a marked shortage in His supply, in addition to the suboptimal milk provision
      of Arg, Gly and Ala.

PMID- 21198959
TI  - Fish meal--nutritive value.
AB  - Understanding the interactions between nutrition and immune system is crucial for
      adjusting nutrient allowances in dietary formulations that optimize production
      efficiency. Among various animal proteins, fish meal (FM) is rich in protein
      (amino acids), readily available throughout most of the world, and competitively
      priced against other animal proteins (e.g. milk and blood). In addition, many
      researchers reported that FM is traditionally recognized as a high digestible
      protein with a high content of amino acids, vitamins and minerals for pigs.
      Supplementation of fatty acids by FM and fish oil (FO) is one strategy to modify
      an animal immune response. As a result of FM and FO effects, those
      supplementations can result in improved performance and immunity of young
      animals.

PMID- 21198960
TI  - Effects of tripeptides and lactogenic hormones on oligopeptide transporter 2 in
      bovine mammary gland.
AB  - This study was conducted to investigate the expression of oligopeptide
      transporter 2 (PepT2) and its potential function in bovine mammary gland. First,
      the PepT2 mRNA and protein were determined in cultured mammary epithelial cells.
      Then the effects of lactogenic hormones (prolactin, hydrocortisone or insulin)
      and substrate (threonyl-phenylalanyl-phenylalanine) on PepT2 were investigated.
      The PepT2 mRNA and protein were successfully detected in bovine mammary
      epithelial cells. PepT2 gene expression was enhanced by the addition of 50, 500
      and 5000 ng/ml prolactin, 10 and 100 ng/ml hydrocortisone, and 50, 500, 5000 and
      50,000 ng/ml insulin. PepT2 mRNA abundance was increased when 5, 10 and 15% of
      threonyl-phenylalanyl-phenylalanine was included. Responses of PepT2 to
      lactogenic hormones and oligopeptide inferred that it may play an important role
      in bovine mammary gland.

PMID- 21198962
TI  - Validation of two ELISA assays for total ghrelin measurement in dogs.
AB  - The aim of this study was to validate two commercially available ELISA assays for
      total ghrelin measurement in dogs: one canine-specific and one originally
      designed for measuring human ghrelin. The two assays showed intra-assay
      coefficient of variations (CVs) lower than 10%, while the inter-assay CVs
      exceeded the 15% limit. Sample dilutions resulted in linear regression equations
      with correlation coefficients close to 1. In order to compare methods and verify
      ability of the ghrelin assays to differentiate between low and high levels,
      ghrelin concentrations were measured in plasma samples obtained before and at
      different times after glucose administration in five Beagle dogs. A statistically
      significant changes in ghrelin after glucose administration was recorded only
      with assay B. In conclusion, the human ELISA validated in this study showed a
      good intra-assay precision, accuracy, and when applied to the glucose injection
      study, was better in distinguishing high and low canine ghrelin levels than the
      canine ELISA assay.

PMID- 21198961
TI  - Plasma leptin and mRNA expression of lipogenesis and lipolysis-related factors in
      bovine adipose tissue around parturition.
AB  - The objective was to study changes in plasma leptin concentration parallel to
      changes in the gene expression of lipogenic- and lipolytic-related genes in
      adipose tissue of dairy cows around parturition. Subcutaneous fat biopsies were
      taken from 27 dairy cows in week 8 antepartum (a.p.), on day 1 postpartum (p.p.)
      and in week 5 p.p. Blood samples were assayed for concentrations of leptin and
      non-esterified fatty acids (NEFA). Subcutaneous adipose tissue was analysed for
      mRNA abundance by real-time qRT-PCR encoding for leptin, adiponectin receptor 1
      (AdipoR1), adiponectin receptor 2 (AdipoR2), hormones-sensitive lipase (HSL),
      perilipin (PLIN), lipoprotein lipase (LPL), acyl-CoA synthase long-chain family
      member 1 (ACSL1), acetyl-CoA carboxylase (ACC), fatty acid synthase (FASN) and
      glycerol-3-phosphate dehydrogenase 2 (GPD2). Body weight and body condition score
      of the cows were lower after parturition than before parturition. The calculated
      energy balance was negative in week 1 and 5 p.p., with higher negative energy
      balance in week 1 p.p. compared with that in week 5 p.p. On day 1 p.p., highest
      concentrations of NEFA (353.3 MUmol/l) were detected compared with the other
      biopsy time-points (210.6 and 107.7 MUmol/l, in week 8 a.p., and week 5 p.p.
      respectively). Reduced plasma concentrations of leptin during p.p. when compared
      with a.p. would favour increasing metabolic efficiency and energy conservation
      for mammary function and reconstitution of body reserves. Lower mRNA abundance of
      ACC and FASN expression on day 1 p.p. compared with other biopsy time-points
      suggests an attenuation of fatty acid synthesis in subcutaneous adipose tissue
      shortly after parturition. Gene expression of AdipoR1, AdipoR2, HSL, PLIN, LPL,
      ACSL1 and GPD2 was unchanged over time.

PMID- 21198963
TI  - Effect of incremental levels of fish oil supplementation on specific bacterial
      populations in bovine ruminal fluid.
AB  - The objective of this study was to determine the effects of incremental
      replacement of dietary linoleic acid by >20-carbon polyunsaturated fatty acids
      (PUFA) on changes in population of ruminal micro-organisms associated with fibre
      digestion and biohydrogenation using real-time PCR of bacterial 16S rRNA
      sequences. Four beef steers with ruminal cannulas were randomly assigned to
      control (CK, 65:35 forage to concentrate), CK with 3% sunflower oil plus 1% fish
      oil (S3F1), 2.5% sunflower oil plus 1.5% fish oil (S2.5F1.5) or 2% sunflower oil
      plus 2% fish oil (S2F2) in a 4 * 4 Latin square design with 21-day periods.
      Ruminal fluid was collected on day 15 of each period. Compared with CK, oil
      addition led to lower ruminal acetate and butyrate but greater propionate
      concentration. DNA copy number of Anaerovibrio lipolytica in ruminal fluid was
      greater with oil (average 5.38 vs. 3.62 * 10(5) DNA copy number), particularly
      with S2F2 relative to CK. Fibrobacter succinogenes and Butyrivibrio fibrisolvens
      DNA copy number decreased by 74% (1.06 vs. 4.01 * 10(5)) and 39% (5.16 vs. 8.42 *
      10(7)) in response to S2F2 compared with CK. DNA copy numbers of Ruminococcus
      flavefaciens and Ruminococcus albus were not affected by incremental fish oil.
      Results suggest that greater availability of PUFA with >20 carbons (i.e.
      eicosapentaenoic acid and docosahexaenoic acid) promoted changes in bacterial
      populations that are relevant for fibre digestion and biohydrogenation.

PMID- 21198964
TI  - Fat source affects growth of weanling rats fed high-fat diets low in zinc.
AB  - In two 3-week experiments with a 2-factorial design, weanling rats were fed semi
      purified diets in which the zinc concentration was either suboptimal or adequate
      for maximum growth. In experiment 1, one low-fat diet and four diets enriched
      with 26% beef tallow (BT), butterfat (BF), coconut oil or sunflower oil (SF) were
      compared. The low-Zn SF diet did not support growth. The animals fed the high-Zn
      SF diet had the lowest final weights among all other groups, and their serum and
      femur Zn concentrations were markedly depressed. In experiment 2, the low- and
      high-Zn diets were enriched with 18% BT, SF, BT + SF (1:1 w/w), or olive oil
      (OL). Final live weights showed a Zn * fat source interaction. The low-Zn SF and
      OL groups consumed less food and weighed less than the low-Zn BT group. At the
      high-Zn level, final weights were comparable among groups. Serum and femur Zn
      concentrations did not significantly vary among groups fed diets with the same Zn
      level. Possibilities for the growth-retarding effect of the diets rich in
      unsaturated fatty acids (SF and OL) are discussed. Metabolic studies are needed
      to clarify the observed zinc * fat source interaction.

PMID- 21198965
TI  - Influences of increased levels of biotin, zinc or mannan-oligosaccharides in the
      diet on foot pad dermatitis in growing turkeys housed on dry and wet litter.
AB  - Foot pad dermatitis (FPD) is very common in turkeys and it is an animal health
      and welfare issue affecting not only performance and walking ability but also the
      carcass quality. Thus, there is a great need to find out the preventive measures
      against this problem. The potential roles of extra dietary biotin, Zn and mannan
      oligosaccharides (MOS) in preventing the development of FPD were assessed in this
      study which was conducted on 2-week-old female turkeys over a period of 4 weeks.
      The birds were allotted to four groups, with 29 each, and housed on dry wood
      shavings in floor pens. The turkeys were fed a control (300 MUg biotin and 50 mg
      Zn/kg), high biotin (2000 MUg/kg), high Zn (150 mg/kg) or MOS (1%) diet. Half of
      the turkeys in each group were additionally exposed to wet litter (27% DM) for 8
      h daily in adjacent separate boxes. Foot pads of the birds were examined on days
      0, 7, 14, 21 and 28 and assessed macroscopically and histopathologically for foot
      pad lesions. High dietary levels of biotin or Zn significantly reduced the
      severity of FPD on dry litter (score 1 vs. 2 in control) but not on wet litter.
      However, MOS did not affect the severity of foot pad lesions either on dry or wet
      litter. In addition, the severity was overall substantially higher on wet
      (approximately three times) than on dry litter. The present results suggest that
      adding high levels of biotin or Zn to the diet could reduce the development and
      severity of FPD on dry litter but without having any preventive effects on wet
      litter. Finally, the high litter moisture appears to be the major factor
      resulting in FPD. Therefore, the litter should be maintained dry to minimize the
      prevalence and severity of FPD in turkeys.

PMID- 21198966
TI  - Glycaemic and insulinaemic responses to feeding hay with different non-structural
      carbohydrate content in control and polysaccharide storage myopathy-affected
      horses.
AB  - The aim of this study was to determine whether the glycaemic/insulinaemic
      responses to hay with non-structural carbohydrate (NSC, soluble carbohydrate) of
      17% (HC), 10% (MC) or 4% (LC) differs in control horses and whether these
      responses differ between control and horses with polysaccharide storage myopathy
      (PSSM). Five clinically normal control horses and seven PSSM horses, all unfit
      and of Quarter Horse breeding (age 9.4 +/- 3.4 years, body condition score range:
      4.5-6). A crossover design compared the HC and LC hay, with horses randomly
      assigned to hay type for 5 days, and all horses fed the MC hay during washout,
      after which the diets were switched. Horses were fed 1.5% BW (as fed) divided
      into 2 feeding per day, no grain. On morning of the fifth day of each block
      (seventh day for washout), horses were given 0.5% BW in hay, blood was drawn
      before and every 30 min for 5 h after feeding, and the rate of intake was
      measured. Whole blood glucose and plasma insulin were measured. The intake rate
      was significantly higher for HC. In control horses, the insulin area under the
      curve (6891.7 +/- 3524.2 HC vs. 1185.4 +/- 530.2 LC) was significantly higher
      than LC. Polysaccharide storage myopathy horses had significantly higher
      glycaemic and insulinaemic responses to HC vs. LC, however; the magnitude of
      insulin response was lower and glucose response higher in PSSM vs. control
      horses. Results suggest that insulin responses can differ significantly with the
      NSC content of hay. Feeding hay with 17% NSC produces elevations in insulin that
      could be detrimental for PSSM horses.

PMID- 21198968
TI  - Effect of intrauterine infusion with liquid paraffin on phagocytes migrating to
      mucus of external os of the cervix in cows.
AB  - The objective of this study was to investigate the effect of intrauterine
      infusion with liquid paraffin (LP) on phagocytic migration into the uterus of
      cows. Smears of swab samples of the external os of the cervix and discharges
      collected inside the vagina were obtained in multiparous dairy cows (n = 10) that
      had been infused with 50 ml of LP (LP group: n = 5) or physiological saline (PS
      group: n = 5) on day 10 or 11 after ovulation (day 0: ovulation). The samples
      were collected for cytological examination 0 (just before), 0.25, 1, 2, 3, 4, 6,
      8, 12 and 24 h after LP or PS infusion and then at daily intervals until
      subsequent ovulation. The number of neutrophils increased significantly (p <
      0.05) for 8 days compared with the pre-infusion level in the LP group and for 2
      days in the PS group. The average numbers of neutrophils in the LP group were
      significantly (p < 0.05) greater than those in the PS group on 3, 4, 5 and 8 days
      after infusion. The number of monocytes from 6 h to 8 days after LP infusion was
      significantly higher than that before infusion (p < 0.05). The average numbers of
      monocytes at 4 and 6 h and 1 day after infusion in the LP group were
      significantly higher than those in the PS group. These findings indicate that LP
      stimulates phagocytic migration into the uterine lumen in cows and that LP
      infusion into the uterus might enhance uterine defence mechanisms during uterine
      infection.

PMID- 21198969
TI  - Expression of pluripotency genes in buffalo (Bubalus bubalis) amniotic fluid
      cells.
AB  - Recent findings suggest that mammalian amniotic fluid (AF) is a source of
      multipotent stem cells (SCs), which can be used in regenerative medicine and
      assisted reproduction. We report the isolation, culture and characterization of
      amniotic fluid-derived cells from pregnant water buffalo uterus. These
      undifferentiated AF cells expanded without feeder layer over a period of 100 days
      up to passages 20 and the expression of alkaline phosphatase (AP), Oct-4, Nanog
      and Sox-2, GAPDH and beta-actin could be detected by RT-PCR. The cells exhibited
      uniform morphology and normal chromosome number. The up-regulation or down
      regulation of transcription factors of each gene varied with passage number. We
      conclude that putative bubaline AF cells can be cultured and maintained in vitro
      for a prolonged period and offer a potential source of multipotent cells for
      applications including assisted reproduction in buffalo.

PMID- 21198970
TI  - Testicular fluid content evaluated by ultrasound image computer-assisted analysis
      increases with small-dose multiple GnRH injections in rams.
AB  - The aim of the work was to determine whether multiple small doses of GnRH induce
      an increase in testicular blood flow and scrotal temperature in rams. The
      experiment was performed during the late breeding season (May-June) with 14 one
      year-old rams. Seven rams received hourly doses of 7 ng of a GnRH analogue
      (busereline acetate) iv starting at 8:00 on the morning, and the other seven rams
      remained as controls. One week later, treatments were overcrossed. One hour
      before the first GnRH dose (7:00), and 0, 1, 2, 4, 7 and 10 h later,
      ultrasonographic examinations of the testes were performed with a B-mode
      ultrasound scanner with a 7.5 MHz linear array transducer. Each testicle was
      examined separately by placing the transducer vertically. Images were analysed
      with specific software using the spot metering technique in four spots with a
      diameter of 1 cm on the same place of the image. At the same times, rectal, anal
      and scrotal surface temperatures were measured with a laser thermometer. Pixel
      intensity was lower with time (blacker, p < 0.0001), as a consequence of GnRH
      treatment (p < 0.0001). Differences between pixel intensities were significant
      starting 1 h after the first GnRH dose (p < 0.0001). Perineal temperature (33.9
      +/- 0.2 degrees C) was not affected by treatment or time (p > 0.1). Rectal
      temperature was similar in both groups (p < 0.05) until 4 h after the beginning
      of the treatment (13:00 h). The differences between treatments increased since 4
      h after the first dose of GnRH. Scrotal surface temperatures were not affected by
      treatment (p > 0.1). We concluded that multiple small GnRH doses trigger a rapid
      increase in testicular fluid content not accompanied by changes on scrotal
      surface temperature.

PMID- 21198971
TI  - The expression of thrombopoietin and its receptor during different physiological
      stages in the bovine ovary.
AB  - Thrombopoietin (TPO) is known to be involved in megakaryocytopoiesis, but its
      role in the control of ovarian function is unknown in cattle. The aims of this
      study were to demonstrate the expression of TPO and its receptor (c-MPL) in
      detail in bovine corpus luteum (CL) obtained from different stages of the
      oestrous cycle and during pregnancy--and to demonstrate that TPO/c-MPL system is
      expressed clearly in bovine follicles. Real-time RT-PCR (qPCR) and ELISA were
      applied to investigate mRNA expression of examined factors and TPO protein,
      respectively. In this investigation, increases in the concentrations of TPO
      protein and the mRNA expression of TPO and c-MPL were noticed during both early
      luteal stage and late luteal stage of the oestrous cycle. Furthermore, the
      expression of TPO/c-MPL system does not show any significant regulation in the CL
      throughout pregnancy. Highest co-expression of TPO/c-MPL system in both theca
      interna (TI) and granulosa cells (GC) in small follicles (<10 mm in diameter) was
      observed in this study that may suggest the possible role of TPO/c-MPL system in
      proliferation of TI and GC cells. To conclude, the results demonstrate the
      possible involvement of locally produced TPO/c-MPL system as a 'physiological
      filter' in bovine ovary where they may promote cell selection by inducing
      proliferation of viable cells and scavenging non-viable cells and thereby may
      play an important role in modulation of ovarian function.

PMID- 21198972
TI  - The comparison of antioxidative/oxidative profile in blood, colostrum and milk of
      early post-partum cows and their newborns.
AB  - Act of delivery is supposed to be connected with antioxidative/oxidative
      imbalance not only in female but also in her newborn. The aim of the study was to
      compare antioxidative/oxidative profile of cows and their newborns in blood,
      colostrum and milk during early post-partum period. Twenty-five healthy pregnant
      cows and their newborns were included into study. Blood and colostrum/milk
      samples were obtained immediately after parturition, 24, 48 h as well as 6 and 12
      days post-partum. Parameters of antioxidative defence including total antioxidant
      capacity (TAC) and glutathione peroxidase (GSH-Px) as well as parameters of lipid
      (LPI) and protein (SH) peroxidation intensity were determined
      spectrophotometrically. Obtained results indicated dynamic changes in values of
      examined parameters during time of experiment, which were significantly marked
      between 24 and 48 h post-partum, and the relationship between mother and her
      newborn. All parameters except for GSH-Px were markedly higher in blood of
      newborns as in their mothers. Moreover, TAC and GSH-Px in colostrum were lower as
      in blood of mothers and their newborns during first 24 h and showed opposite
      relationship later on. LPI was higher in colostrum as in plasma of mothers and
      their newborns during first 48 h, while SH was lower in colostrum as in plasma of
      examined animals. Values of antioxidative parameters increased significantly
      within examined period of time, while the content of SH groups tended to decrease
      and lipid peroxidation intensity fluctuated. Dynamics in changes of examined
      parameters may suggest temporary imbalance in antioxidative/oxidative status and
      adequate answer of organism to current challenge resulting from overproduction of
      reactive oxygen species. Present study may bring new knowledge into studies of
      post-parturient and post-natal period in cows and calves and may help preventing
      from diseases of this period.

PMID- 21198973
TI  - Effects of season and superovulatory treatment on embryo yields in fine-wool
      Merinos maintained under field conditions.
AB  - The aim of the study was to assess the effects of superovulatory treatment
      (multiple FSH-dose vs single-shot FSH treatment) and seasonality on embryo yields
      in fine-wool Merino ewes. Treatment based on multiple FSH-dose consisted of 200
      mg of FSH (Folltropin((r))) administered in seven decreasing doses. Single-shot
      treatment consisted of a single dose of 70 mg of FSH + eCG. In ewes treated with
      multiple FSH doses, number of recovered embryos was higher (6.0 +/- 0.5 vs 3.5 +/
      1.0), while non-fertilization rate was lower (12.8 +/- 3.9 vs 40.3 +/- 9.5)
      during the breeding season when compared to the non-breeding season (p < 0.05);
      although similar values of recovered Grades 1-2 embryos were observed between
      seasons. During the breeding season, proportion of responding ewes (98.1 vs
      57.1%), ovulation rate (13.9 +/- 0.8 vs 3.2 +/- 1.2), recovered structures (7.9
      +/- 0.6 vs 1.7 +/- 0.7), total recovered embryos (6.0 +/- 0.5 vs 1.2 +/- 0.6) and
      good-quality embryos (5.1 +/- 0.5 vs 0.9 +/- 0.6) were higher for the multiple
      FSH-dose treatment than for the single-shot protocol. In a similar way, in the
      non-breeding season, ovulation rate (11.3 +/- 1.8 vs 6.0 +/- 1.1) and recovered
      structures (6.6 +/- 1.2 vs 2.7 +/- 0.6) were higher for the multiple FSH
      injections protocol than those for the single-shot treatment, resulting in higher
      recovered Grades 1-2 embryos (3.2 +/- 0.9 vs 1.4 +/- 0.5). Current results
      indicate that seasonal anestrus affected embryo yields when applying multiple FSH
      dose superovulatory treatment in Merino ewes, by decreasing the number of
      recovered embryos although the number of recovered good-quality embryos was not
      affected. During both seasons, multiple FSH injections produced higher ovarian
      response and number of viable embryos than the single-shot treatment.

PMID- 21198974
TI  - The role of oocyte-secreted factors GDF9 and BMP15 in follicular development and
      oogenesis.
AB  - Ovarian physiology is controlled by endocrine and paracrine signals, and the
      transforming growth factor beta (TGFbeta) superfamily has a pivotal role in this
      control. The Bone morphogenetic protein 15 (BMP15) and Growth differentiation
      factor 9 (GDF9) genes are relevant members of the TGFbeta superfamily that encode
      proteins secreted by the oocytes into the ovarian follicles. Through a paracrine
      signalling pathway, these factors induce the follicular somatic cells to undergo
      mitosis and differentiation during follicular development. These events are
      controlled by a mutually dependent and coordinated fashion during the formation
      of the granulosa cell layers. Many studies have contributed to our knowledge
      concerning the paracrine factors acting within the follicular environment,
      especially regarding GDF9 and BMP15. We aimed to review the relevant
      contributions of these two genes to animal reproductive physiology.

PMID- 21198975
TI  - Quantifying reward with transcranial magnetic stimulation (commentary on Gupta
      and Aron).

PMID- 21198976
TI  - An fMRI investigation of detection of semantic incongruities in autistic spectrum
      conditions.
AB  - The aim of this study was to investigate differences in the brain's haemodynamic
      response to semantically incongruent and congruent sentences in adults with an
      autistic spectrum condition (ASC) and a typically developing Control group. We
      used functional magnetic resonance imaging to measure regional variations in
      neural activity during detection of semantic incongruities within written
      sentences. Whilst the 12 controls showed a pattern of activity extending from
      posterior cingulate cortices bilaterally and the left occipitotemporal region to
      the left superior and inferior temporal lobes, right anterior cingulate and right
      inferior frontal gyrus, the 12 participants with an ASC presented a more
      spatially restricted activation pattern, including the left inferior frontal
      gyrus, left anterior cingulate cortex and right middle frontal gyrus. These
      results are coherent with the hypothesis that impaired integration of multiple
      neural networks in people with an ASC is related to previous observations that
      this group have difficulties in the use of context to predict the final word of
      sentences.

PMID- 21198977
TI  - Neurogranin phosphorylation fine-tunes long-term potentiation.
AB  - Learning-related potentiation of synaptic strength at Cornu ammonis subfield 1
      (CA1) hippocampal excitatory synapses is dependent on neuronal activity and the
      activation of glutamate receptors. However, molecular mechanisms that regulate
      and fine-tune the expression of long-term potentiation (LTP) are not well
      understood. Recently it has been indicated that neurogranin (Ng), a neuron
      specific, postsynaptic protein that is phosphorylated by protein kinase C,
      potentiates synaptic transmission in an LTP-like manner. Here, we report that a
      Ng mutant that is unable to be phosphorylated cannot potentiate synaptic
      transmission in rat CA1 hippocampal neurons and results in a submaximal
      expression of LTP. Our results provide the first evidence that the
      phosphorylation of Ng can regulate LTP expression.

PMID- 21198978
TI  - Contribution of the mouse calyx of Held synapse to tone adaptation.
AB  - The calyx of Held synapse is a giant synapse in the medial nucleus of the
      trapezoid body (MNTB) of the ventral brainstem, which is involved in sound
      localization. Although it has many release sites, it can show transmission
      failures and display an increase in synaptic delay during high-frequency
      signalling. Its apparent lack of reliability and precision raises the question
      whether this synapse makes a sizeable contribution to tone adaptation, the
      decline in response to sustained or repetitive auditory stimuli. We observed
      evidence for the presence of both ipsilateral and contralateral inhibition, but
      these effects were already present in the inputs to the MNTB, suggesting that
      synaptic inhibition within the MNTB does not contribute to tone adaptation.
      During trains of brief tones at variable intervals, there were no clear changes
      in reliability or precision at tone intervals of 20 ms or longer. A progressive
      decrease in the number of spikes measured in the MNTB was observed at shorter
      tone intervals, but this decrease largely originated upstream from the MNTB. In
      addition, for tones with short intervals, during the train a progressive increase
      in first-spike latencies was observed, but much smaller changes were observed in
      the delay between excitatory postsynaptic potentials and postsynaptic action
      potentials within the MNTB. We conclude that despite the failures and variability
      in synaptic delay that are present at the calyx of Held synapse, their
      contribution to tone adaptation is relatively small compared with upstream
      factors.

PMID- 21198979
TI  - Exercise impacts brain-derived neurotrophic factor plasticity by engaging
      mechanisms of epigenetic regulation.
AB  - We have evaluated the possibility that the action of voluntary exercise on the
      regulation of brain-derived neurotrophic factor (BDNF), a molecule important for
      rat hippocampal learning, could involve mechanisms of epigenetic regulation. We
      focused the studies on the Bdnf promoter IV, as this region is highly responsive
      to neuronal activity. We have found that exercise stimulates DNA demethylation in
      Bdnf promoter IV, and elevates levels of activated methyl-CpG-binding protein 2,
      as well as BDNF mRNA and protein in the rat hippocampus. Chromatin
      immunoprecipitation assay showed that exercise increases acetylation of histone
      H3, and protein assessment showed that exercise elevates the ratio of acetylated
      :total for histone H3 but had no effects on histone H4 levels. Exercise also
      reduces levels of the histone deacetylase 5 mRNA and protein implicated in the
      regulation of the Bdnf gene [N.M. Tsankova et al. (2006)Nat. Neurosci., 9, 519
      525], but did not affect histone deacetylase 9. Exercise elevated the
      phosphorylated forms of calcium/calmodulin-dependent protein kinase II and cAMP
      response element binding protein, implicated in the pathways by which neural
      activity influences the epigenetic regulation of gene transcription, i.e. Bdnf.
      These results showing the influence of exercise on the remodeling of chromatin
      containing the Bdnf gene emphasize the importance of exercise on the control of
      gene transcription in the context of brain function and plasticity. Reported
      information about the impact of a behavior, inherently involved in the daily
      human routine, on the epigenome opens exciting new directions and therapeutic
      opportunities in the war against neurological and psychiatric disorders.

PMID- 21198980
TI  - Enhanced brainstem encoding predicts musicians' perceptual advantages with pitch.
AB  - Important to Western tonal music is the relationship between pitches both within
      and between musical chords; melody and harmony are generated by combining pitches
      selected from the fixed hierarchical scales of music. It is of critical
      importance that musicians have the ability to detect and discriminate minute
      deviations in pitch in order to remain in tune with other members of their
      ensemble. Event-related potentials indicate that cortical mechanisms responsible
      for detecting mistuning and violations in pitch are more sensitive and accurate
      in musicians as compared with non-musicians. The aim of the present study was to
      address whether this superiority is also present at a subcortical stage of pitch
      processing. Brainstem frequency-following responses were recorded from musicians
      and non-musicians in response to tuned (i.e. major and minor) and detuned (+/- 4%
      difference in frequency) chordal arpeggios differing only in the pitch of their
      third. Results showed that musicians had faster neural synchronization and
      stronger brainstem encoding for defining characteristics of musical sequences
      regardless of whether they were in or out of tune. In contrast, non-musicians had
      relatively strong representation for major/minor chords but showed diminished
      responses for detuned chords. The close correspondence between the magnitude of
      brainstem responses and performance on two behavioral pitch discrimination tasks
      supports the idea that musicians' enhanced detection of chordal mistuning may be
      rooted at pre-attentive, sensory stages of processing. Findings suggest that
      perceptually salient aspects of musical pitch are not only represented at
      subcortical levels but that these representations are also enhanced by musical
      experience.

PMID- 21198981
TI  - Photoperiod interacts with food restriction in performance in the Barnes maze in
      female California mice.
AB  - Food restriction has been reported to have positive effects on cognition. This
      study examines how another environmental factor, daylength, can alter the impact
      of food restriction on the brain and behavior. Female California mice (Peromyscus
      californicus), housed on either long days (16 h of light and 8 h of darkness) or
      short days (8 h of light and 16 h of darkness), were restricted to 80% of their
      normal baseline food intake or provided with food ad libitum. Testing in a Barnes
      maze revealed that the effects of food restriction depended on photoperiod, and
      that these effects differed for acquisition vs. reversal learning. During
      acquisition testing, food restriction increased latency to finding the target
      hole in short-day mice but not in long-day mice. In reversal testing, food
      restriction decreased latency to finding the target hole in long-day mice but not
      in short-day mice. Latency to finding the hole was positively and independently
      correlated with both errors and time spent freezing, suggesting that changes in
      both spatial learning and anxiety-like behavior contributed to performance. Short
      days increased hippocampal expression of the synaptic protein, synapsin I, which
      was reversed by food restriction. Short days also reduced plasma corticosterone
      levels, but diet had no effect. There was no effect of diet or photoperiod on
      hippocampal expression of the glial marker, glial fibrillary acidic protein. The
      present findings suggest that, in female California mice, the differential
      effects of food restriction on acquisition and reversal learning are photoperiod
      dependent. These results justify further testing of the relationship between food
      restriction and hippocampal synapsin I in the context of spatial learning.

PMID- 21198982
TI  - Vascular endothelial growth factor up-regulation in the mouse hippocampus and its
      role in the control of epileptiform activity.
AB  - The vascular endothelial growth factor (VEGF) signalling pathway may represent an
      endogenous anti-convulsant in the rodent hippocampus although its exact
      contribution requires some clarification. In mouse hippocampal slices, the
      potassium channel blocker 4-aminopyridine (4-AP) in the absence of external
      Mg(2+)(0 Mg(2+)) produces both ictal and interictal activity followed by a
      prolonged period of repetitive interictal activity. In this model, we
      demonstrated that exogenous VEGF has clear effects on ictal and interictal
      activity as it reduces the duration of ictal-like events, but decreases the
      frequency and intensity of interictal discharges. VEGF affects epileptiform
      activity through its receptor VEGFR-2. We also demonstrated for the first time
      that the synaptic action of VEGF in the hippocampus is through VEGFR-2-mediated
      effects on NMDA and GABA(B) receptors and that VEGF does not affect the NMDA
      excytatory postsynaptic potential paired-pulse facilitation ratio. Exogenous VEGF
      does not affect the AMPA-mediated responses and the dendritic or the somatic
      GABA(A) inhibitory postsynaptic potentials. In addition, VEGF drastically reduces
      0 Mg(2+)/4-AP-induced glutamate release through VEGFR-2 activation. In vitro
      epileptiform activity is sufficient to increase hippocampal expression of VEGF
      and VEGFR-2, and this up-regulation may serve a neuroprotective and/or anti
      convulsant role. VEGFR-2 up-regulation has been localized to the CA1 region,
      which suggests that VEGF signalling may protect CA1 pyramidal cells from
      hyperexcitability. These results indicate that VEGF controls epileptic activity
      by influencing both glutamatergic and GABAergic transmission and further advance
      our understanding of the conditions required for endogenous VEGF up-regulation,
      and the mechanisms by which VEGF achieves an anti-convulsant effect.

PMID- 21198984
TI  - Organization of GABAergic inhibition in the motor output layer of the superior
      colliculus.
AB  - The direction and amplitude of saccadic eye movements are determined by the
      location of the center of gravity of burst activity over a neuronal population on
      the spatial map of the intermediate gray layer (SGI) of the superior colliculus
      (SC). GABAergic interneurons might play critical roles in shaping the activation
      field on the topographical map but, to understand the mechanism, basic
      information on the organization of inhibitory circuits is essential. In the
      present study, we investigated the electrophysiological and morphological
      properties of GABAergic neurons in SGI by whole-cell patch-clamp recordings and
      intracellular staining using biocytin in GAD67-GFP knock-in mice (PND17-22), in
      which GABAergic neurons specifically express GFP fluorescence. The most common
      firing properties among these GABAergic neurons (n=231) were fast spiking (58%),
      followed by burst spiking (29%), late spiking (8%) and, the least common, regular
      spiking (2%) and rapid spike inactivation (3%). Morphological analysis of axonal
      trajectories of intracellularly-labeled GABAergic neurons revealed three major
      subclasses: (i) intralaminar interneurons, which were further divided into two
      subclasses, local and horizontal interneurons; (ii) interlaminar interneurons;
      and (iii) commissural and tectofugal neurons. These results reveal distinct
      subsets of GABAergic neurons including neurons that mediate local and long-range
      inhibition in the SC, neurons that potentially modulate visual and other sensory
      inputs to the SC, and neurons that project to nuclei outside the SC.

PMID- 21198983
TI  - Nucleus accumbens neurons encode predicted and ongoing reward costs in rats.
AB  - Efficient decision-making requires that animals consider both the benefits and
      the costs of potential actions, such as the amount of effort or temporal delay
      involved in reward seeking. The nucleus accumbens (NAc) has been implicated in
      the ability to choose between options with different costs and overcome high
      costs when necessary, but it is not clear how NAc processing contributes to this
      role. Here, neuronal activity in the rat NAc was monitored using multi-neuron
      electrophysiology during two cost-based decision tasks in which either reward
      effort or reward delay was manipulated. In each task, distinct visual cues
      predicted high-value (low effort/immediate) and low-value (high effort/delayed)
      rewards. After training, animals exhibited a behavioral preference for high-value
      rewards, yet overcame high costs when necessary to obtain rewards.
      Electrophysiological analysis indicated that a subgroup of NAc neurons exhibited
      phasic increases in firing rate during cue presentations. In the effort-based
      decision task (but not the delay-based task), this population reflected the cost
      discounted value of the future response. In contrast, other subgroups of cells
      were activated during response initiation or reward delivery, but activity did
      not differ on the basis of reward cost. Finally, another population of cells
      exhibited sustained changes in firing rate while animals completed high-effort
      requirements or waited for delayed rewards. These findings are consistent with
      previous reports that implicate NAc function in reward prediction and behavioral
      allocation during reward-seeking behavior, and suggest a mechanism by which NAc
      activity contributes to both cost-based decisions and actual cost expenditure.

PMID- 21198985
TI  - Cholinergic and non-cholinergic mesopontine tegmental neurons projecting to the
      subthalamic nucleus in the rat.
AB  - The subthalamic nucleus (STN) receives cholinergic and non-cholinergic
      projections from the mesopontine tegmentum. This study investigated the numbers
      and distributions of neurons involved in these projections in rats using
      Fluorogold retrograde tracing combined with immunostaining of choline
      acetyltransferase and a neuron-specific nuclear protein. The results suggest that
      a small population of cholinergic neurons mainly in the caudoventral part of the
      pedunculopontine tegmental nucleus (PPN), approximately 360 neurons (~ 10% of the
      total) in the homolateral and 80 neurons (~ 2%) in the contralateral PPN,
      projects to the STN. In contrast, the number of non-cholinergic neurons
      projecting to the STN was estimated to be nine times as much, with approximately
      3300 in the homolateral side and 1300 in the contralateral side. A large
      gathering of the Fluorogold-labeled non-cholinergic neurons was found
      rostrodorsomedial to the caudolateral PPN. The biotinylated dextran amine (BDA)
      anterograde tracing method was used to substantiate the mesopontine-STN
      projections. Injection of BDA into the caudoventral PPN labeled numerous thin
      fibers with small en-passant varicosities in the STN. Injection of BDA into the
      non-cholinergic neuron-rich area labeled a moderate number of thicker fibers with
      patches of aggregates of larger boutons. The densities of labeled fibers and the
      number of retrogradely labeled cells in the mesopontine tegmentum suggested that
      the terminal field formed in the STN by each cholinergic neuron is more extensive
      than that formed by each non-cholinergic neuron. The findings suggest that
      cholinergic and non-cholinergic mesopontine afferents may carry different
      information to the STN.

PMID- 21198986
TI  - Bcl-2 homology domain 3-only proteins Puma and Bim mediate the vulnerability of
      CA1 hippocampal neurons to proteasome inhibition in vivo.
AB  - Bcl-2 homology domain 3 (BH3)-only proteins are pro-apoptotic Bcl-2 family
      members that play important roles in upstream cell death signalling during
      apoptosis. Proteasomal stress has been shown to contribute to the pathology of
      cerebral ischaemia and many neurodegenerative disorders. Here we explored the
      contribution of BH3-only proteins in mediating proteasome-inhibition-induced
      apoptosis in the murine brain in vivo. Stereotactic intrahippocampal
      microinjection of the selective proteasome inhibitor epoxomicin (2.5 nmol)
      induced a delayed apoptosis within only the CA1 hippocampal neurons and not
      neurons within the CA3 or dentate gyrus regions, a selective vulnerability
      similar to that seen during ischaemia. This injury developed over a time-course
      of 3 days and was characterized by positive terminal deoxynucleotidyl transferase
      dUTP nick end labelling staining and nuclear condensation. Previous work from our
      laboratory has identified the BH3-only protein p53-upregulated mediator of
      apoptosis (Puma) as mediating proteasome-inhibition-induced apoptosis in cultured
      neural cells. Genetic deletion of puma reduced the number of terminal
      deoxynucleotidyl transferase dUTP nick end labelling-positive cells within the
      CA1 following epoxomicin microinjection but it did not provide a complete
      protection. Subsequent studies identified the BH3-only protein Bim as also being
      upregulated during proteasome inhibition in organotypic hippocampal slice
      cultures and after epoxomicin treatment in vivo. Interestingly, the genetic
      deletion of bim also afforded significant neuroprotection, although this
      protection was less pronounced. In summary, we demonstrate that the BH3-only
      proteins Puma and Bim mediate the delayed apoptosis of CA1 hippocampal neurons
      induced by proteasome inhibition in vivo, and that either BH3-only protein can
      only partly compensate for the deficiency of the other.

PMID- 21198987
TI  - Development of monotonic neuronal tuning in the monkey inferotemporal cortex
      through long-term learning of fine shape discrimination.
AB  - Visual expertise in discriminating fine differences among a group of similar
      objects can be obtained through extensive long-term training. Here we
      investigated the neural bases of this superior capability. The inferotemporal
      cortex, located at the final stage along the ventral visual pathway, was a
      candidate site in monkeys because cells there respond to various complex features
      of objects. To identify the changes that underlie the development of visual
      expertise in fine discrimination, we created a set of parametrically designed
      object stimuli and compared the stimulus selectivity of inferotemporal cells
      between two different training histories. One group of recordings was conducted
      after the monkeys had been extensively trained for fine discrimination (fine
      discrimination period) and the other after the monkeys had been exposed only for
      coarse discrimination (coarse-discrimination period). We found that the tuning of
      responses recorded in the fine-discrimination period was more monotonic in the
      stimulus parameter space. The stimuli located at the extreme in the parameter
      space evoked the maximum responses in a larger proportion of cells and the
      direction of response decrease in the parameter space was more consistent.
      Moreover, the stimulus arrangement reconstructed from the responses recorded
      during the fine-discrimination period was more similar to the original stimulus
      arrangement. These results suggest that visual expertise could be based on the
      development, in the inferotemporal cortex, of neuronal selectivity monotonically
      tuned over the parameter space of the object images.

PMID- 21198988
TI  - Rapid increases of gamma power in the auditory cortex following noise trauma in
      humans.
AB  - Tinnitus is an auditory perception in the absence of any external sound source.
      It has been suggested that tinnitus is related to enhanced synchronization of
      neuronal activity in the auditory cortex. Usually a hearing damage can be
      identified suggesting auditory deprivation to central auditory regions to be
      fundamental for neurophysiological processes related to tinnitus. Until now,
      human research has been conducted on patients with chronic tinnitus (>6 months).
      However, neuronal activity accompanying auditory deprivation and putatively
      tinnitus may not remain constant over time, making it difficult to directly
      relate outcomes of current animal studies (acute tinnitus) to chronic tinnitus in
      humans, and vice versa. We investigated 14 amateur rock musicians who frequently
      reported a short-term tinnitus immediately after band practice.
      Magnetoencephalographic resting-state recordings, audiometry and tinnitus testing
      were performed at two separate occasions: with and without previous exposure to
      loud music. Analyses revealed that transient tinnitus was accompanied by
      temporary hearing loss in both ears and increased gamma activity in the right
      auditory cortex in 13 out of 14 cases. Additionally, tinnitus frequency was
      strongly correlated to hearing loss. Analogous to animal studies, our results
      show for the first time in humans that noise trauma leads rapidly to increased
      neuronal synchrony in the auditory cortex. Importantly, the strongly right
      lateralized effect implies that it does not reflect tinnitus percept per se. This
      could rather have been triggered by greater discontinuities of hearing loss at
      high frequencies that were particularly pronounced in the left ear.

PMID- 21198989
TI  - Somatosensory inputs modify auditory spike timing in dorsal cochlear nucleus
      principal cells.
AB  - In addition to auditory inputs, dorsal cochlear nucleus (DCN) pyramidal cells in
      the guinea pig receive and respond to somatosensory inputs and perform
      multisensory integration. DCN pyramidal cells respond to sounds with
      characteristic spike-timing patterns that are partially controlled by rapidly
      inactivating potassium conductances. Deactivating these conductances can modify
      both spike rate and spike timing of responses to sound. Somatosensory pathways
      are known to modify response rates to subsequent acoustic stimuli, but their
      effect on spike timing is unknown. Here, we demonstrate that preceding tonal
      stimulation with spinal trigeminal nucleus (Sp5) stimulation significantly alters
      the first spike latency, the first interspike interval and the average discharge
      regularity of firing evoked by the tone. These effects occur whether the neuron
      is excited or inhibited by Sp5 stimulation alone. Our results demonstrate that
      multisensory integration in DCN alters spike-timing representations of acoustic
      stimuli in pyramidal cells. These changes likely occur through synaptic
      modulation of intrinsic excitability or synaptic inhibition.

PMID- 21198991
TI  - Prognostic value of the Geneva prediction rule in patients in whom pulmonary
      embolism is ruled out.
AB  - OBJECTIVES: The prognosis of patients in whom pulmonary embolism (PE) is
      suspected but ruled out is poorly understood. We evaluated whether the initial
      assessment of clinical probability of PE could help to predict the prognosis for
      these patients. DESIGN: Retrospective analysis of data obtained during a
      prospective multicentre management study. SETTING: Six general and teaching
      hospitals in Belgium, France and Switzerland. SUBJECTS: In 1334 patients in whom
      PE was ruled out, 3-month mortality data were available (hospital readmission
      status was unknown for three patients) and clinical probability was evaluated
      with the revised Geneva score (RGS). MAIN OUTCOME MEASURES: Three-month mortality
      and readmission rates. RESULTS: Three-month mortality and readmissions rates were
      3% and 19%, respectively and differed significantly depending on the RGS
      determined PE probability group (P<0.001). When compared with patients presenting
      with a low probability, the risk of death after 3 months was higher in cases of
      intermediate or high RGS-based probability {odds ratio: 8.7 [95% confidence
      interval (CI): 2.7-28.5] and 22.6 (95%CI: 2.1-241.2), respectively}. The
      readmission risk increased with PE probability group (P<0.001). The main causes
      of death were cancer, respiratory failure and cardiovascular failure. In total,
      86% of patients with low RGS-based probability were alive and had not been
      readmitted to hospital, whereas other patients had a twofold increased risk of
      death or readmission during the 3-month follow-up. The simplified Geneva score,
      calculated a posteriori, gave similar results. CONCLUSIONS: Initial assessment of
      clinical probability may help to stratify prognosis of patients in whom PE has
      been ruled out. Patients with a low probability of PE have a good prognosis.
      Whether patients with higher probability might benefit from more vigilant care
      should be evaluated.

PMID- 21198990
TI  - Metabotropic glutamate receptor blockade in nucleus accumbens shell shifts
      affective valence towards fear and disgust.
AB  - Glutamatergic inputs to the nucleus accumbens (NAc) modulate both appetitive and
      fearful motivation. It has been suggested that pathological disturbances of
      glutamate signaling in NAc contribute to motivation disorders, ranging from
      excessive desire in drug addiction to paranoia in schizophrenia. Metabotropic
      glutamate receptors are of special interest, as metabotropic Group II receptor
      (mglu2/3) agonists have been proposed as potential treatments for both addiction
      and schizophrenia. Here we tested whether local mglu2/3 receptor blockade in the
      medial shell of the rat NAc can generate intense distortions of motivation or
      affect, which might model clinical dysfunction. We found that microinjection of
      the mglu2/3 antagonist LY341495 at sites throughout medial shell suppressed
      appetitive motivation to eat and drink. Simultaneously, LY341495 microinjections
      generated fearful motivation in the form of defensive treading or burying. To
      assess whether the valence shift extended into a parallel hedonic shift from
      affective 'liking' to 'disliking' we employed the taste reactivity test, which
      measures affective orofacial reactions to the sensory pleasure or displeasure of
      tastes. We found that LY341495 microinjections reduced positive 'liking'
      reactions to sucrose and enhanced 'disliking' reactions. Overall, mglu2/3
      antagonism at most shell sites produced a similar valence shift from positive to
      negative. This pattern comprised (i) generation of fearful behaviors, and (ii)
      induction of aversive affective reactions, together with (iii) loss of appetitive
      ingestion and (iv) loss of 'liking' for rewards. These results are discussed in
      terms of implications for clinical disorders and the influence of corticolimbic
      glutamate inputs to NAc in the generation of motivation and affect.

PMID- 21198992
TI  - A panel of biomarkers including caspase-3 and D-dimer may differentiate acute
      stroke from stroke-mimicking conditions in the emergency department.
AB  - BACKGROUND AND AIMS: At present, a rapid and widely available diagnostic test for
      stroke remains elusive. The aim of this study was to examine the predictive value
      of a panel of blood-borne biochemical markers for stroke diagnosis. DESIGN:
      Consecutive patients with strokes or stroke-mimicking conditions (mimics) were
      evaluated within 24 h from symptom onset (915 strokes and 90 mimics). Blood
      samples were analysed by enzyme-linked immunosorbent assay for C-reactive
      protein, d-dimer, soluble receptor for advanced glycation end products (sRAGE),
      metalloproteinase 9 (MMP-9), S100B, brain natriuretic peptide, caspase-3,
      neurotrophin-3, chimerin and secretagogin. RESULTS: The main independent
      predictors of stroke versus mimics were caspase-3 >1.96 ng mL(-1) [odds ratio
      (OR) = 3.32; 95% confidence interval (CI) 1.88-5.88, P < 0.0001], d-dimer >0.27
      MUg mL(-1) (OR = 2.97; 95% CI 1.72-5.16, P = 0.0001), sRAGE >0.91 ng mL(-1) (OR =
      2.19; 95% CI 1.26-3.83, P = 0.006), chimerin <1.11 ng mL(-1) (OR = 0.4; 95% CI
      0.19-0.81, P = 0.011), secretagogin <0.24 ng mL(-1) (OR = 0.51; 95% CI 0.27-0.97,
      P = 0.041) and MMP-9 > 199 ng mL(-1) (OR = 1.66; 95% CI 1.01-2.73, P = 0.046).
      The model's predictive probability of stroke when the six biomarkers are
      above/below these cut-off levels was 99.01%. The best combination of biomarkers
      in the model was caspase-3 and d-dimer. Moreover, a model developed for samples
      obtained within the first 3 h showed high sensitivity (Se) and specificity (Sp)
      (threshold at 25th percentile: Se 0.87, Sp 0.55; threshold at 75th percentile: Se
      0.28, Sp 0.99). CONCLUSIONS: A combination of biomarkers including caspase-3 and
      d-dimer appears to be the most promising to achieve a rapid biochemical diagnosis
      of stroke. If replicated, this approach could be used as a tool for urgent
      referral of stroke patients to hospitals in which acute treatments are available.

PMID- 21198993
TI  - Nonfasting cholesterol and triglycerides and association with risk of myocardial
      infarction and total mortality: the Copenhagen City Heart Study with 31 years of
      follow-up.
AB  - OBJECTIVES: We compared the ability of very high levels of nonfasting cholesterol
      and triglycerides to predict risk of myocardial infarction and total mortality.
      DESIGN: Prospective study from 1976 to 1978 until 2007. SETTING: Danish general
      population. PARTICIPANTS: Randomly selected population of 7581 women and 6391
      men, of whom 768 and 1151 developed myocardial infarction and 4398 and 4416 died,
      respectively. Participation rate was 72%, and follow-up was 100% complete. Less
      than 2% of participants were taking lipid-lowering therapy. RESULTS: Compared to
      women with cholesterol <5 mmol L(-1) , multivariate-adjusted hazard ratios for
      myocardial infarction ranged from 1.3 [95% confidence interval (CI): 0.9-1.8] for
      a cholesterol level of 5.0-5.99 mmol L(-1) to 2.5 (95%CI: 1.6-4.0) for
      cholesterol >= 9 mmol L(-1) (trend: P < 0.0001). Compared with women with
      nonfasting triglycerides <1 mmol L(-1) , hazard ratios for myocardial infarction
      ranged from 1.5 (95%CI: 1.2-1.8) for triglycerides of 1.0-1.99 mmol L(-1) to 4.2
      (95%CI: 2.5-7.2) for triglycerides >= 5 mmol L(-1) (p<0.0001). In men,
      corresponding hazard ratios ranged from 1.2 (95%CI: 1.0-1.5) to 5.3 (95%CI: 3.6
      8.0) for cholesterol (P < 0.0001) and from 1.3 (95%CI: 1.0-1.6) to 2.1 (95%CI:
      1.5-2.8) for triglycerides (P < 0.0001). Increasing cholesterol levels were not
      consistently associated with total mortality in women (trend: P = 0.39) or men (P
      = 0.02). By contrast, compared with women with triglycerides <1 mmol L(-1) ,
      multivariate-adjusted hazard ratios for total mortality ranged from 1.1 (95%CI:
      1.0-1.2) for triglycerides of 1.0-1.99 mmol L(-1) to 2.0 (95%CI: 1.5-2.9) for
      triglycerides >=5 mmol L(-1) (trend: P < 0.0001); corresponding hazard ratios in
      men ranged from 1.1 (95%CI: 1.0-1.2) to 1.5 (95%CI: 1.2-1.7) (P < 0.0001).
      CONCLUSIONS: Stepwise increasing levels of nonfasting cholesterol and nonfasting
      triglycerides were similarly associated with stepwise increasing risk of
      myocardial infarction, with nonfasting triglycerides being the best predictor in
      women and nonfasting cholesterol the best predictor in men. Even more
      surprisingly, only increasing levels of nonfasting triglycerides were associated
      with total mortality, whereas increasing cholesterol levels were not.

PMID- 21198994
TI  - Screening for hepatocellular carcinoma in acute intermittent porphyria: a 15-year
      follow-up in northern Sweden.
AB  - OBJECTIVES: To evaluate the benefit of screening for hepatocellular carcinoma
      (HCC) in gene carriers of acute intermittent porphyria (AIP) and estimate the
      annual incidence of HCC in this group. SUBJECTS: All AIP gene carriers aged >=55
      years from the northernmost county in Sweden, Norrbotten, were invited for
      screening in this prospective study every 1-1.5 years during the period 1994
      2009. We registered all HCC cases amongst AIP gene carriers in the northern
      region of Sweden (four counties). We compared gene carriers with repeated
      screening intervals of <2 years (Group A) with controls (Group B; i.e. gene
      carriers who had never been screened, those screened for the first time or
      screened at intervals of >2 years, or dropouts). The screening included
      radiological examination of the liver and relevant laboratory tests. RESULTS: A
      total of 62 AIP subjects participated in the study, comprising 33% of the total
      AIP population aged >55 years in the northern region of Sweden. HCC was diagnosed
      in 22 AIP subjects (12 men and 10 women), mean age 69 (59-82) years. Amongst
      these subjects, 73% had experienced prior AIP attacks. The incidence rate ratio
      for HCC was 64 (52 in men and 93 in women). There were no cases of hepatitis B/C
      or alcohol abuse. Liver cirrhosis was rare. Liver resection could be performed in
      most subjects in Group A. Fourteen patients died of HCC, one in Group A and 13 in
      Group B. Compared with those who were not screened regularly, screening was
      associated with improved 3-year and 5-year survival (P = 0.005 and 0.038).
      CONCLUSIONS: Screening for HCC in carriers of AIP enables early diagnosis and a
      choice of potentially curative treatments with improved prognosis. We recommend
      annual screening using liver imaging for AIP gene carriers >50 years of age.

PMID- 21198995
TI  - Adiponectin in relation to insulin sensitivity and insulin secretion in the
      development of type 2 diabetes: a prospective study in 64-year-old women.
AB  - OBJECTIVES: To examine how serum adiponectin levels predict the incidence of type
      2 diabetes, from different prediabetic states, in relation to insulin sensitivity
      and beta-cell function during 5.5 years of follow-up. METHODS: In a population
      based cohort of 64-year-old Caucasian women, we assessed glucose tolerance,
      insulin sensitivity as homeostasis model assessment, insulin secretion as acute
      insulin response, lifestyle factors and serum concentrations of adiponectin and
      high-sensitivity C-reactive protein. After 5.5 years of follow-up, 167 women with
      normal glucose tolerance (NGT) and 174 with impaired glucose tolerance (IGT) at
      baseline were re-examined and incidence of diabetes was assessed. RESULTS: A
      total of 69 new cases of diabetes were detected during follow-up. Diabetes
      incidence was independently predicted by low levels of serum adiponectin, insulin
      resistance and insulin secretion, cigarette smoking, impaired fasting glucose
      (IFG) and IGT at baseline. Serum adiponectin below 11.54 g L(-1) was associated
      with an odds ratio of 3.6 (95% confidence interval 1.4-8.6) for future type 2
      diabetes. At baseline, a high serum adiponectin concentration correlated
      positively with high levels of insulin sensitivity and insulin secretion. Women
      with incident diabetes had lower serum adiponectin levels in the NGT, IFG and IGT
      groups at baseline compared to those who did not develop diabetes during follow
      up. CONCLUSIONS: Low adiponectin concentrations were associated with future
      diabetes independently of insulin secretion and sensitivity, as well as IGT, IFG,
      smoking and abdominal obesity.

PMID- 21198996
TI  - Cellular cohesiveness in benign and malignant thyroid follicular tumours varies
      significantly, but the difference is not useful in diagnosis of individual cases.
AB  - INTRODUCTION: The aim of our study was to search for new, readily available and
      statistically reliable cytological markers for differentiating benign and
      malignant follicular thyroid neoplasms pre-operatively. METHODS: Cohesiveness of
      tumour cells in cytology slides from a series of 58 follicular tumours diagnosed
      between 1998 and 2004 inclusive was studied, including 48 follicular adenomas,
      and eight minimally invasive and two widely invasive follicular carcinomas.
      Photomicrographs of the cytology slides were taken and the digital images were
      analysed using computer image analysis software. We evaluated the relative
      proportions of cells arranged in groups of various sizes. The cohesiveness of the
      cells in cytological smears was then correlated with the immunohistochemical
      expression of E-cadherin in corresponding histological slides. RESULTS: Cases
      from 15 men (26%) and 43 women (74%) with a mean age of 50 years (range, 19-79)
      were analysed. In follicular adenomas and carcinomas, respectively, isolated
      cells were seen in 16.8% and 24.7% (P = 0.028), groups of two to five cells in
      9.7% and 11.5% (P = 0.145) and groups of more than five cells in 73.5% and 63.8%
      (P = 0.041). The mean cell count in groups with more than five cells was 46.5 and
      27.0 in adenomas and carcinomas, respectively (P < 0.001). Cell cohesiveness,
      either as percentage of cells in groups of more than five (R(2) = 0.026) or as
      mean cell count per group of more than five (R(2) = 0.005), was not found to be
      dependent on the expression of E-cadherin. Using a threshold of 13% isolated
      tumour cells in cytological smears, follicular adenomas and carcinomas could be
      distinguished with 90% sensitivity and 41% specificity. CONCLUSIONS: Although we
      demonstrated a statistically significant difference in cell cohesion between
      follicular adenomas and carcinomas, these could not be distinguished in the
      clinical setting by evaluation of the percentage of isolated cells in cytological
      smears because the specificity was too low. The absence of correlation of
      cellular cohesiveness with E-cadherin expression indicates that other factors are
      probably responsible for the loss of cohesiveness observed in follicular thyroid
      malignancy.

PMID- 21198997
TI  - Abstracts of the XXVIII Annual Scientific Meeting of the British Blood
      Transfusion Society. September 9-11, 2010. Bournemouth, United Kingdom.

PMID- 21198998
TI  - Establishing RHD zygosity in India: a step into the future of foetal and neonatal
      haemolytic disease prevention.
AB  - BACKGROUND: Determination of RHD zygosity is important for the prevention of
      haemolytic disease of foetus and neonate. There is no data from India regarding
      the prevalence of RHD genotypes. OBJECTIVES: We conducted this study to
      investigate RHD zygosity in phenotypically RhD positive (RhD+) Indians. We have
      also investigated the utility and concordance of two different genotyping
      techniques. METHODS: Hundred serologically RhD+ Indians were genotyped at the RHD
      gene using polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) and polymerase chain reaction-sequence-specific primer (PCR-SSP)
      techniques. RESULTS: Of the 100 RhD+ individuals, 26 (25%) were D heterozygous by
      both methods and 74 (71.2%) were D homozygous. There was no discordance in the
      results from the two techniques. CONCLUSION: At least 25% of RhD+ Indians are
      heterozygous at the RHD gene. Both the genotyping techniques were equally robust
      and their complete concordance indicates RHD deletion as the main mechanism
      underlying RhD negativity in Indians.

PMID- 21198999
TI  - Procoagulant activity of long-term stored red blood cells due to
      phosphatidylserine exposure.
AB  - OBJECTIVE/BACKGROUND: Phosphatidylserine (PS) exposure on the outer membrane
      surface is a known storage lesion of red blood cells (RBCs). Procoagulant
      activity (PCA) of PRBC units has been shown to increase during storage. However,
      the PCA and the relation to PS of banked RBCs remain unknown. The aim of this
      study is to investigate the PCA and the correlation with PS exposure on banked
      RBCs. MATERIALS AND METHODS: Human normal leucodepleted RBC concentrates were
      stored in saline-adenine-glucose-mannitol (SAGM) solution at 4  degrees C for up
      to 42 days. PS exposure was measured by lactadherin and annexin V. PCA of RBCs
      was determined by one-step recalcification assay and further determined by
      prothrombinase and tenase assays. The correlation between PCA and PS exposure of
      RBCs was measured by inhibition tests with lactadherin or annexin V. RESULTS:
      Lactadherin detected 1.5% PS-positive stored RBCs vs 0.5% for annexin V after 14
      days of storage, which significantly reached 18.4 vs 4.5% after 42 days of
      storage. Potent PCA was observed on day 14 and continuously increased. PCA of
      RBCs on day 42 was inhibited 94% by lactadherin vs 45% by annexin V. Incubation
      at 37  degrees C in fresh heparinised plasma partially reversed PS exposure and
      PCA of RBCs stored for 14 days but had no effect on these parameters for cells
      stored for 42 days. CONCLUSIONS: PCA and PS exposure of stored RBCs increased
      during storage and showed significant positive correlation. PCA of long-term
      stored RBCs may not be reversed by transfusion.

PMID- 21199001
TI  - Abstracts of the Australasian Professional Society on Alcohol and other Drugs
      Conference 2010. November 28-December 1, 2010. Canberra, Australia.

PMID- 21199003
TI  - Comparative analysis of pyrosequencing and QMC-PCR in conjunction with high
      resolution melting for KRAS/BRAF mutation detection.
AB  - Mutation detection is important in cancer management. Several methods are
      available of which high resolution melting (HRM) analysis and pyrosequencing are
      the most versatile. We undertook a comparative analysis of these techniques. The
      methods are: To compare the limit of detection (LOD), mutations in KRAS (codon
      12/13 hotspot) and BRAF (V600E hotspot) were tested. DNA mixtures containing
      mutant alleles at a frequency of around 25%/12.5%/6%/3%/ 1.5%/0.8% were analysed.
      To compare frequency of mutation detection, 22 DNA samples (nine high quality
      samples from cell lines, 13 low quality samples from formalin-fixed paraffin
      embedded tissue) were tested for three hotspots in KRAS (codons 12/13, 61 and
      146) and two hotspots in BRAF (V600E and exon 11). HRM analysis of KRAS
      (codon12/13) and BRAF (V600E) showed that 3% and 1.5% mutant alleles respectively
      could be reliably detected whilst pyrosequencing reliably detected 6% mutant
      alleles in each case. Of 110 tests performed on 22 DNA samples, in 109 cases HRM
      and pyrosequencing gave identical results. Two of the samples tested had
      previously been called as wild type for KRAS by direct Sanger sequencing but were
      found to be mutant by both HRM and pyrosequencing. Both HRM and pyrosequencing
      can detect small numbers of mutant alleles although HRM has a lower limit of
      detection. Both are suitable for use in mutation detection and are both more
      sensitive than Sanger sequencing.

PMID- 21199004
TI  - Isolation and characterization of Streptococcus mitis from blood of child with
      osteomyelitis.
AB  - OBJECTIVES: Osteomyelitis is an inflammatory process accompanied by bone
      destruction that is caused by bacterial infection, with most child cases showing
      a haematogenous origin and metaphysis of the long bones. The aim of the present
      study was to characterize streptococcal strains isolated from the blood of a
      child diagnosed with osteomyelitis in a long bone and investigate the biological
      properties related to virulence of strains associated with osteomyelitis.
      METHODS: Blood isolate species were determined based on the 16S rRNA sequence.
      Next, the blood isolates were analysed for phagocytosis susceptibility by
      polymorphonuclear leukocytes, platelet aggregation, inhibitory effects on
      osteoblastic cells, and their properties of adhesion with cells, and compared to
      the reference strain Streptococcus mitis ATCC49456. RESULTS: The blood isolates
      were found to be a single clone (named SA1101), which was determined to be S.
      mitis. The phagocytosis susceptibility of SA1101 was significantly lower than
      that of ATCC49456, while its platelet aggregation rate was higher. Furthermore,
      SA1101 showed an inhibitory effect toward the growth of osteoblastic cells and
      had greater properties of adhesion to those cells as compared to ATCC49456.
      CONCLUSIONS: These results suggest that S. mitis SA1101 is a possible etiological
      agent and caused osteomyelitis in the present case.

PMID- 21199005
TI  - Anaphase-promoting complex/cyclosome controls HEC1 stability.
AB  - OBJECTIVE: Chromosome segregation during mitosis requires a physically large
      proteinaceous structure called the kinetochore to generate attachments between
      chromosomal DNA and spindle microtubules. It is essential for kinetochore
      components to be carefully regulated to guarantee successful cell division.
      Depletion, mutation or dysregulation of kinetochore proteins results in mitotic
      arrest and/or cell death. HEC1 (high expression in cancer) has been reported to
      be a kinetochore protein, depletion of which, by RNA interference, results in
      catastrophic mitotic exit. MATERIALS AND METHODS AND RESULTS: To investigate how
      HEC1 protein is controlled post-translation, we analysed the role of anaphase
      promoting complex/cyclosome (APC/C)-Cdh1 in degradation of HEC1 protein. In this
      study, we show that HEC1 is an unstable protein and can be targeted by endogenous
      ubiquitin-proteasome system in HEK293T cells. Results of RNA interference and in
      vivo ubiquitination assay indicated that HEC1 could be ubiquitinated and degraded
      by APC/C-hCdh1 E3 ligase. The evolutionally conserved D-box at the C-terminus
      functioned as the degron of HEC1, destruction of which resulted in resistance to
      degradation mediated by APC/C-Cdh1. Overexpression of non-degradable HEC1 (D-box
      destroyed) induced accumulation of cyclin B protein in vivo and triggered mitotic
      arrest. CONCLUSION: APC/C-Cdh1 controls stability of HEC1, ensuring normal cell
      cycle progression.

PMID- 21199006
TI  - Foe turned friend: multiple functional roles attributable to hyper-activating
      stem cell factor receptor mutant in regeneration of the haematopoietic cell
      compartment.
AB  - OBJECTIVES: Stem cell factor receptor, c-kit, is considered to be the master
      signalling molecule of haematopoietic stem cells. It develops the orchestral
      pattern of haematopoietic cell lineages, seen by its varying degree of
      omnipresence in progenitors, lineage committed and mature cells. We have
      investigated the effect of over-expressing c-kit on early recovery of the
      haematopoietic compartment, in irradiated hosts. MATERIALS AND METHODS: Normal
      bone marrow cells (BMCs) were transfected with Kit(wt) (wild-type c-kit) or its
      variant Kit(mu) (asp814tyr) by electroporation. Lethally irradiated mice were
      transplanted with normal or transfected congeneic BMCs. The effect of ectopic
      expression of c-kit on haematopoietic cell recovery was determined by analysing
      donor-derived cells. Furthermore, effects of both types of c-kit over-expression
      on progenitor and lineage-committed cells were examined by flow cytometric
      analysis of Sca-1 and lineage-committed (Lin(+)) cells respectively. RESULTS:
      Hyper-activating Kit(mu) significantly improved recovery of the haematopoietic
      system in irradiated hosts. In vivo results showed that the donor-derived c
      kit(+) cell population was increased to more than 3-fold in the case of Kit(mu)
      transfected cells compared to normal and Kit(wt) over-expressing BMCs. In
      general, survival of progenitor and committed cell was improved in the Kit(mu)
      over-expressing system compared to the other two cohorts. CONCLUSION: These
      results suggest that recruitment of the hyper-activating variant of c-kit
      (Kit(mu)) lead to early recovery of the bone marrow of lethally irradiated mice.

PMID- 21199007
TI  - Characterization of immortalized mesenchymal stem cells derived from foetal
      porcine pancreas.
AB  - Islet replacement therapy is limited by shortage of donor islet cells. Usage of
      islet cells derived from porcine pancreatic stem cells (PSCs) is currently viewed
      as the most promising alternative for human islet transplantation. However, PSCs
      are rare and have a finite proliferative lifespan. In this study, we isolated and
      established an immortalized mesenchymal stem cell (MSC) line derived from foetal
      porcine pancreas, by transfecting human telomerase reverse transcriptase (hTERT)
      and called these immortalized pancreatic mesenchymal stem cells (iPMSCs). The
      iPMSCs have been cultured for more than 80 passages and have capacity to
      differentiate into neurons, cardiomyocytes, germ cells and islet-like cells,
      analysed by morphology, RT-PCR, western blotting, immunofluorescence,
      immunocytochemistry and transplantation assay. Islets derived from iPMSCs
      reversed hyperglycaemia in streptozotocin-induced diabetic mice and secreted
      insulin and C-peptide in vitro. These results demonstrated that iPMSCs might
      provide unlimited resources for islet replacement therapy and models for
      functional cell differentiation.

PMID- 21199008
TI  - Fibrin acts as biomimetic niche inducing both differentiation and stem cell
      marker expression of early human endothelial progenitor cells.
AB  - OBJECTIVES: Transplantation of endothelial progenitor cells (EPCs) is a promising
      approach for revascularization of tissue. We have used a natural and
      biocompatible biopolymer, fibrin, to induce cell population growth,
      differentiation and functional activity of EPCs. MATERIALS AND METHODS:
      Peripheral blood mononuclear cells were cultured for 1 week to obtain early EPCs.
      Fibrin was characterized for stiffness and capability to sustain cell population
      expansion at different fibrinogen-thrombin ratios. Viability, differentiation and
      angiogenic properties of EPCs were evaluated and compared to those of EPCs grown
      on fibronectin. RESULTS: Fibrin had a nanometric fibrous structure forming a
      porous network. Fibrinogen concentration significantly influenced fibrin
      stiffness and cell growth: 9 mg/ml fibrinogen and 25 U/ml thrombin was the best
      ratio for enhanced cell viability. Moreover, cell viability was significantly
      higher on fibrin compared to being on fibronectin. Even though no significant
      difference was observed in expression of endothelial markers, culture on fibrin
      elicited marked induction of stem cell markers OCT 3/4 and NANOG. In vitro
      angiogenesis assay on Matrigel showed that EPCs grown on fibrin retain
      angiogenetic capability as EPCs grown on fibronectin, but significantly better
      release of cytokines involved in cell recruitment was produced by EPC grown on
      fibrin. CONCLUSION: Fibrin is a suitable matrix for EPC growth, differentiation
      and angiogenesis capability, suggesting that fibrin gel may be very useful for
      regenerative medicine.

PMID- 21199009
TI  - Extracellular transglutaminase 2 has a role in cell adhesion, whereas
      intracellular transglutaminase 2 is involved in regulation of endothelial cell
      proliferation and apoptosis.
AB  - OBJECTIVE: Transglutaminase 2 (TG2) is a multifunctional protein with an
      important role in vascular biology, where it is involved in cell-matrix
      interaction, cell attachment and cell population expansion. In efforts to
      elucidate the role of TG2 in endothelial cell biology, in this study, we measured
      several endothelial cell characteristics in cells where TG2 was specifically
      knocked down by RNAi. MATERIALS AND METHODS: The effect of small interfering RNA
      (siRNA)-TG2 on human umbilical vein endothelial cells was studied. Adhesion and
      cell viability were assessed by chemical reduction of MTT, and cell proliferation
      was analysed by flow cytometry. Apoptosis was evaluated by annexin V/PI dual
      staining and protein expression level was assayed by western blotting. RESULTS:
      We found that siRNA-TG2 reduced endothelial cell number, lead to cell adhesion
      deficiency, cell cycle arrest in G1 phase and induction of apoptosis. Our results
      show that exogenously added TG2 could reverse loss of adhesion but did not
      overcome the defect in cell proliferation, nor could it inhibit siRNA-TG2-induced
      apoptosis. CONCLUSION: We conclude that TG2 loss in endothelial cells causes
      reduction in cell number as a result of cell cycle arrest, flaws in adhesion and
      induction of apoptosis. Our results imply that reduction in cell number and
      increased apoptosis in response to TG2 silencing is independent of the cell
      adhesion process. Altogether, our findings underline the significance of TG2 in
      endothelial cell cycle progression and cell survival, in vitro.

PMID- 21199010
TI  - MicroRNA signatures associated with immortalization of EBV-transformed
      lymphoblastoid cell lines and their clinical traits.
AB  - OBJECTIVE: MicroRNAs (miRNAs) are negative regulators of gene expression that
      play important roles in cell processes such as proliferation, development and
      differentiation. Recently, it has been reported that miRNAs are related to
      development of carcinogenesis. The aim of this study was to identify miRNAs
      associated with terminal immortalization of Epstein-Barr virus (EBV)-transformed
      lymphoblastoid cell line (LCL) and associated clinical traits. MATERIAL AND
      METHODS: Hence, we performed miRNA microarray approach with early- (p6) and late
      passage (p161) LCLs. RESULTS AND CONCLUSION: Microarray data showed that nine
      miRNAs (miR-20b*, miR-28-5p, miR-99a, miR-125b, miR-151-3p, miR-151:9.1, miR
      216a, miR-223* and miR-1296) were differentially expressed in most LCLs during
      long-term culture. In particular, miR-125b was up-regulated in all the tested
      late-passage LCLs. miR-99a, miR-125b, miR-216a and miR-1296 were putative
      negative regulators of RASGRP3, GPR160, PRKCH and XAF1, respectively, which were
      found to be differentially expressed in LCLs during long-term culture in a
      previous study. Linear regression analysis showed that miR-200a and miR-296-3p
      correlated with triglyceride and HbA1C levels, respectively, suggesting that
      miRNA signatures of LCLs could provide information on the donor's health. In
      conclusion, our study suggests that expression changes of specific miRNAs may be
      required for terminal immortalization of LCLs. Thus, differentially expressed
      miRNAs would be a potential marker for completion of cell immortalization during
      EBV-mediated tumorigenesis.

PMID- 21199011
TI  - Early spontaneous immortalization and loss of plasticity of rabbit bone marrow
      mesenchymal stem cells.
AB  - OBJECTIVES: Bone marrow-derived mesenchymal stem cells (BM-MSC) have been widely
      used for cell therapy and tissue engineering purposes. However, there are still
      controversies concerning safety of application of these cells after in vitro
      expansion. Therefore, we aimed to investigate the characteristics of rabbit BM
      MSC during long-term culture. MATERIALS AND METHODS: In this study, we have
      examined growth kinetics, morphological changes, differentiation potential and
      chromosomal abnormalities, as well as tumour formation potential of rabbit BM-MSC
      in long-term culture. RESULTS AND CONCLUSION: We found that shortly after
      isolation, proliferation rate of rabbit BM-MSC decreases until they enter a
      dormant phase. During this period of quiescence, the cells are large and
      multinucleate. After some weeks of dormancy we found that several small
      mononuclear cells originated from each large multinucleate cell. These newly
      formed cells proliferated rapidly but had inferior differentiation potential.
      Although they were immortal, they did not have the capability for tumour
      formation in soft agar assay or in nude mice. This is the first report of
      spontaneous, non-tumorigenic immortalization of BM-MSC in rabbits. The phenomenon
      raises more concern for meticulous monitoring and quality control for using
      rabbit BM-MSC in cell-based therapies and tissue engineering experiments.

PMID- 21199012
TI  - Effect of long-term culture of mouse embryonic stem cells under low oxygen
      concentration as well as on glycosaminoglycan hyaluronan on cell proliferation
      and differentiation.
AB  - OBJECTIVES: Maintaining undifferentiated stem cells in defined conditions is of
      critical importance to improve their in vitro culture. We have evaluated the
      effects of culturing mouse stem (mES) cells under physiological oxygen
      concentration as well as by replacing fibroblast feeder layer (mEF) with gelatin
      or glycosaminoglycan hyaluronan (HA), on cell proliferation and differentiation.
      MATERIALS AND METHODS: After 3 days culture or after long-term cell culture under
      different conditions, levels of apoptotic cell death were determined by cell
      cycle and TUNEL (TdT-mediated dUTP nick end labelling) assays and levels of cell
      proliferation by CFSE (5-(and-6)-carboxyfluorescein diacetate succinimidyl ester)
      labelling. We assessed spontaneous differentiation into cardiomyocytes and mRNA
      expression of pluripotency and differentiation biomarkers. RESULTS: After 3 days
      culture under hypoxic conditions, levels of proliferation and apoptosis of mES
      cells were higher, in correlation with increase in intracellular reactive oxygen
      species. However, when cells were continuously grown for 1 month under those
      conditions, the level of apoptosis was, in all cases, under 4%. Hypoxia reduced
      spontaneous differentiation of mES into cardiomyocytes. Long-term culture on HA
      was more effective in maintaining the pluripotent state of the mES cells when
      compared to that on gelatin. Level of terminal differentiation was highest on
      mEF, intermediate on HA and lowest on gelatin. CONCLUSIONS: Our data suggest that
      hypoxia is not necessary for maintaining pluripotency of mES cells and appeared
      to be detrimental during ES differentiation. Moreover, HA may offer a valuable
      alternative for long-term culture of mES cells in vitro.

PMID- 21199013
TI  - Adipose-derived stem cells for clinical applications: a review.
AB  - The use of stem cells derived from adipose tissue as an autologous and self
      replenishing source for a variety of differentiated cell phenotypes, provides a
      great deal of promise for reconstructive surgery. In this article, we review
      available literature encompassing methods of extraction of pluripotent adipose
      stem cells (ASCs) from lipoaspirate locations, their storage, options for
      culture, growth and differentiation, cryopreservation and its effect on stem cell
      survival and proliferation, and new technologies involving biomaterials and
      scaffolds. We will conclude by assessing potential avenues for developing this
      incredibly promising field.

PMID- 21199014
TI  - In vitro mesenchymal stem cell differentiation after mechanical stimulation.
AB  - OBJECTIVES: Mesenchymal stem cells (MSC) are multipotent cells capable of
      differentiating into adipocytic, chondrocytic and osteocytic lineages on suitable
      stimulation. We have hypothesized that mechanical loading may influence MSC
      differentiation and alter their phenotype accordingly. MATERIALS AND METHODS:
      Mouse bone marrow-derived MSC were established in vitro by differential adherence
      to plastic culture plates and grown in low glucose medium with 10% foetal calf
      serum and growth factors. Cells grew out and were subcultured up to 20 times.
      Differentiation protocols were followed for several cell lineages. Clones with
      trilineage potential were seeded in type I collagen gels and incubated in a
      tensioning force bioreactor and real-time cell-derived forces were recorded. Gels
      were fixed and sectioned for light and electron microscopy. RESULTS: Cell
      monolayers of parent and cloned mouse bone marrow-derived MSC differentiated into
      adipocytes, osteocytes and chondrocytes, but not into cardiomyocytes, myotubes or
      neuronal cells. When cast into type I collagen gels and placed in tensioning
      bioreactors, MSC differentiated into fibroblast-like cells typical of tissue
      stroma, and upregulated alpha-smooth muscle actin, but rarely upregulated desmin.
      Electron microscopy showed collagen and elastin fibre synthesis into the matrix.
      CONCLUSIONS: These experiments confirmed that MSC cell fate choice depends on
      minute, cell-derived forces. Applied force could assist in commercial manufacture
      of cultured bio-engineered prostheses for regenerative medicine as it mimics
      tissue stresses and constitutes a good model for development of tissue
      substitutes.

PMID- 21199018
TI  - Analysis of expressed sequence tags from Maize mosaic rhabdovirus-infected gut
      tissues of Peregrinus maidis reveals the presence of key components of insect
      innate immunity.
AB  - The corn planthopper, Peregrinus maidis, causes direct feeding damage to plants
      and transmits Maize mosaic rhabdovirus (MMV) in a persistent-propagative manner.
      MMV must cross several insect tissue layers for successful transmission to occur,
      and the gut serves as an important barrier for rhabdovirus transmission. In order
      to facilitate the identification of proteins that may interact with MMV either by
      facilitating acquisition or responding to virus infection, we generated and
      analysed the gut transcriptome of P. maidis. From two normalized cDNA libraries,
      we generated a P. maidis gut transcriptome composed of 20,771 expressed sequence
      tags (ESTs). Assembly of the sequences yielded 1860 contigs and 14,032
      singletons, and biological roles were assigned to 5793 (36%). Comparison of P.
      maidis ESTs with other insect amino acid sequences revealed that P. maidis shares
      greatest sequence similarity with another hemipteran, the brown planthopper
      Nilaparvata lugens. We identified 202 P. maidis transcripts with putative
      homology to proteins associated with insect innate immunity, including those
      implicated in the Toll, Imd, JAK/STAT, Jnk and the small-interfering RNA-mediated
      pathways. Sequence comparisons between our P. maidis gut EST collection and the
      currently available National Center for Biotechnology Information EST database
      collection for Ni. lugens revealed that a pathogen recognition receptor in the
      Imd pathway, peptidoglycan recognition protein-long class (PGRP-LC), is present
      in these two members of the family Delphacidae; however, these recognition
      receptors are lacking in the model hemipteran Acyrthosiphon pisum. In addition,
      we identified sequences in the P. maidis gut transcriptome that share significant
      amino acid sequence similarities with the rhabdovirus receptor molecule,
      acetylcholine receptor (AChR), found in other hosts. This EST analysis sheds new
      light on immune response pathways in hemipteran guts that will be useful for
      further dissecting innate defence response pathways to rhabdovirus infection.

PMID- 21199019
TI  - Proteomics of cryoprotective dehydration in Megaphorura arctica Tullberg 1876
      (Onychiuridae: Collembola).
AB  - The Arctic springtail, Megaphorura arctica Tullberg 1876 (Onychiuridae:
      Collembola), is one of the few organisms known to survive the extreme stresses of
      its environment by using cryoprotective dehydration. We have undertaken a
      proteomics study comparing M. arctica, acclimated at -2 degrees C, the
      temperature known to induce the production of the anhydroprotectant trehalose in
      this species, and -6 degrees C, the temperature at which trehalose expression
      plateaus, against control animals acclimated at +5 degrees C. Using difference
      gel electrophoresis, and liquid chromatography tandem mass spectrometry, we
      identified three categories of differentially expressed proteins with specific
      functions, up-regulated in both the -2 degrees C and -6 degrees C animals, that
      were involved in metabolism, membrane transport and protein folding. Proteins
      involved in cytoskeleton organisation were only up-regulated in the -6 degrees C
      animals.

PMID- 21199020
TI  - Genetic analysis of the xenobiotic resistance-associated ABC gene subfamilies of
      the Lepidoptera.
AB  - Some ATP-binding cassette (ABC) transporters of subfamilies B, C and G confer
      resistance to xenobiotics including insecticides. We identified genes of these
      subfamilies expressed by the lepidopterans Trichoplusia ni and Bombyx mori. The
      B. mori genome includes eight, six and 13 ABC-B, -C and -G genes, respectively,
      which encode P-glycoprotein, multidrug resistance protein, MRP, and breast cancer
      resistance protein, BCRP, homologues. Among the ABC-C and -G subfamilies, gene
      duplication contributes to protein diversity. We have identified three ABC-B and
      two ABC-C T. ni genes. Analyses of the T. ni MRP (TrnMRP) revealed unique
      features, including the potential for TrnMRP4 hyperglycosylation and the
      alternative splicing of TrnMRP1. Taken together, these attributes of moth
      multidrug resistance-associated ABCs may confer distinct functional capacities to
      xenobiotic efflux.

PMID- 21199021
TI  - The pyrokinin/ pheromone biosynthesis-activating neuropeptide (PBAN) family of
      peptides and their receptors in Insecta: evolutionary trace indicates potential
      receptor ligand-binding domains.
AB  - The pyrokinin/pheromone biosynthesis-activating neuropeptide (PBAN) family of G
      protein-coupled receptors and their ligands have been identified in various
      insects. Physiological functions of pyrokinin peptides include muscle
      contraction, whereas PBAN regulates, among other functions, pheromone production
      in moths which indicates the pleiotropic nature of these peptides. Based on the
      alignment of annotated genomic sequences, the pyrokinin/PBAN family of receptors
      have similarity with the corresponding structures of the capa or periviscerokinin
      receptors of insects and the neuromedin U receptors of vertebrates. In our study,
      evolutionary trace (ET) analysis on the insect receptor sequences was conducted
      to predict the putative ligand recognition and binding sites. The ET analysis of
      four class-specific receptors indicated several amino acid residues that are
      conserved in the transmembrane domains. The receptor extracellular domains
      exhibit several class-specific amino acid residues, which could indicate putative
      domains for activation of these receptors by ligand recognition and binding.

PMID- 21199022
TI  - Effects of Wolbachia on mtDNA variation and evolution in natural populations of
      Tetranychus urticae Koch.
AB  - We investigated the effects of Wolbachia infection on mtDNA variation in spider
      mites by sequencing a portion of the mitochondrial cytochrome oxidase I (COI)
      gene from 198 individuals of known infection status. Four Wolbachia strains were
      described in the current study, namely wUrtOri1, wUrtOri2, wUrtOri3 and wUrtCon1.
      As predicted, the haplotype and nucleotide diversity were lower in infected
      individuals than in uninfected individuals. However, these mtDNA haplotype data
      are not entirely concordant with the surface protein of wolbachia (wsp) sequence
      data and both infected and uninfected individuals were found of the same
      haplotype. Although values of Tajima's D and Fu & Li's F were consistently less
      than zero for most infected groups, McDonald-Kreitman tests suggested that the
      patterns of variation were different from those expected under neutrality in only
      the uninfected group. Thus, the neutrality tests do not show a clear effect of
      Wolbachia infection on patterns of mtDNA variation and substitution in spider
      mites.

PMID- 21199023
TI  - Identification of X-linked quantitative trait loci affecting cold tolerance in
      Drosophila melanogaster and fine mapping by selective sweep analysis.
AB  - Drosophila melanogaster is a cosmopolitan species that colonizes a great variety
      of environments. One trait that shows abundant evidence for naturally segregating
      genetic variance in different populations of D. melanogaster is cold tolerance.
      Previous work has found quantitative trait loci (QTL) exclusively on the second
      and the third chromosomes. To gain insight into the genetic architecture of cold
      tolerance on the X chromosome and to compare the results with our analyses of
      selective sweeps, a mapping population was derived from a cross between
      substitution lines that solely differed in the origin of their X chromosome: one
      originates from a European inbred line and the other one from an African inbred
      line. We found a total of six QTL for cold tolerance factors on the X chromosome
      of D. melanogaster. Although the composite interval mapping revealed slightly
      different QTL profiles between sexes, a coherent model suggests that most QTL
      overlapped between sexes, and each explained around 5-14% of the genetic variance
      (which may be slightly overestimated). The allelic effects were largely additive,
      but we also detected two significant interactions. Taken together, this provides
      evidence for multiple QTL that are spread along the entire X chromosome and whose
      effects range from low to intermediate. One detected transgressive QTL influences
      cold tolerance in different ways for the two sexes. While females benefit from
      the European allele increasing their cold tolerance, males tend to do better with
      the African allele. Finally, using selective sweep mapping, the candidate gene
      CG16700 for cold tolerance colocalizing with a QTL was identified.

PMID- 21199024
TI  - Hybridization and restricted gene flow between native and introduced stocks of
      Alpine whitefish (Coregonus sp.) across multiple environments.
AB  - Translocations of Baltic whitefish (Coregonus sp.) into Austrian Alpine lakes
      have created 'artificial hybrid zones', threatening the genetic integrity of
      native lineages. We evaluate the genetic structure of Coregonus in Austrian lakes
      and characterize hybridization and introgression between native and introduced
      lineages. Fifteen populations (N=747) were assessed for allelic variation at
      eight microsatellite loci and a reduced set (N=253) for variation across two
      mtDNA genes (cyt b and NADH-3). Bayesian approaches were used to estimate
      individual admixture proportions (q-values) and classify genotypes as native,
      introduced or hybrids. q-value distributions varied among populations
      highlighting differential hybridization and introgression histories. Many lakes
      revealed a clear distinction between native and introduced genotypes despite
      hybridization, whereas some locations revealed hybrid swarms. Genetic structure
      among lakes was congruent with morphological divergence and novelty raising
      speculation of multiple taxa, including a population south of the Alps, outside
      the putative native range of Coregonus. Although statistically congruent with
      inferences based on nuclear markers, mitochondrial haplotype data was not
      diagnostic with respect to native and non-native lineages, supporting that the
      Alpine region was colonized post-glacially by an admixture of mtDNA lineages,
      which coalesce >1 Ma. Mechanisms promoting or eroding lineage isolation are
      discussed, as well as a high potential to conserve native Alpine lineages despite
      the extensive historical use of introduced Baltic stocks.

PMID- 21199025
TI  - Interpopulation patterns of divergence and selection across the transcriptome of
      the copepod Tigriopus californicus.
AB  - The accumulation of genetic incompatibilities between isolated populations is
      thought to lead to the evolution of intrinsic postzygotic isolation. The
      molecular basis for these mechanisms, however, remains poorly understood. The
      intertidal copepod Tigriopus californicus provides unique opportunities for
      addressing mechanistic questions regarding the early stages of speciation;
      hybrids between highly divergent populations are fertile and viable, but exhibit
      reduced fitness at the F(2) or later generations. Given the current scarcity of
      genomic information in taxa at incipient stages of reproductive isolation, we
      utilize high-throughout 454 pyrosequencing to characterize a substantial fraction
      of protein-coding regions (the transcriptome) of T. californicus. Our sequencing
      effort was divided equally between two divergent populations in order to estimate
      levels of divergence and to reveal patterns of selection across the
      transcriptome. Assembly of sequences generated over 40,000 putatively unique
      transcripts (unigenes) for each population, 19,622 of which were orthologous
      between populations. BLAST searches of public databases determined protein
      identity and functional features for 15,402 and 12,670 unigenes, respectively.
      Based on rates of nonsynonymous and synonymous substitutions in 5897
      interpopulation orthologs (those >150 bp and with at least 2X coverage), we
      identified 229 potential targets of positive selection. Many of these genes are
      predicted to be involved in several metabolic processes, and to function in
      hydrolase, peptidase and binding activities. The library of T. californicus
      coding regions, annotated with their predicted functions and level of divergence,
      will serve as an invaluable resource for elucidating molecular mechanisms
      underlying the early stages of speciation.

PMID- 21199026
TI  - Evolutionary criteria outperform operational approaches in producing ecologically
      relevant fungal species inventories.
AB  - Analyses of the structure and function of microbial communities are highly
      constrained by the diversity of organisms present within most environmental
      samples. A common approach is to rely almost entirely on DNA sequence data for
      estimates of microbial diversity, but to date there is no objective method of
      clustering sequences into groups that is grounded in evolutionary theory of what
      constitutes a biological lineage. The general mixed Yule-coalescent (GMYC) model
      uses a likelihood-based approach to distinguish population-level processes within
      lineages from processes associated with speciation and extinction, thus
      identifying a distinct point where extant lineages became independent. Using two
      independent surveys of DNA sequences associated with a group of ubiquitous plant
      symbiotic fungi, we compared estimates of species richness derived using the GMYC
      model to those based on operational taxonomic units (OTUs) defined by fixed
      levels of sequence similarity. The model predicted lower species richness in
      these surveys than did traditional methods of sequence similarity. Here, we show
      for the first time that groups delineated by the GMYC model better explained
      variation in the distribution of fungi in relation to putative niche-based
      variables associated with host species identity, edaphic factors, and aspects of
      how the sampled ecosystems were managed. Our results suggest the coalescent-based
      GMYC model successfully groups environmental sequences of fungi into clusters
      that are ecologically more meaningful than more arbitrary approaches for
      estimating species richness.

PMID- 21199027
TI  - Discord reigns among nuclear, mitochondrial and phenotypic estimates of
      divergence in nine lineages of trans-Beringian birds.
AB  - Proposals for genetic thresholds for species delimitation assume that simple
      genetic data sets (e.g. mitochondrial sequence data) are correlated with
      speciation; i.e. such data sets accurately reflect organismal lineage divergence.
      We used taxonomically stratified phenotypic levels of differentiation
      (populations, subspecies and species) among nine avian lineages using paired,
      trans-Beringian samples from three lineages each in three orders (Anseriformes,
      Charadriiformes, and Passeriformes) to test this assumption. Using mitochondrial
      DNA sequence data and nuclear genomic data (amplified fragment length
      polymorphisms), we found a lack of concordance between these two genomes in their
      respective estimates of divergence and little or no relationship between
      phenotype (taxonomic relatedness) and genetic differentiation between taxon
      pairs. There are several possible reasons for the discord observed (e.g.
      selection on one of the genomes or perhaps lineage sorting), but the implications
      are that genetic estimates of lineage divergence may not be correlated with
      estimates from other parts of the genome, are not well correlated with the
      speciation process and are thus not reliable indicators of species limits.

PMID- 21199028
TI  - Isolation and differentiation of Rivulus hartii across Trinidad and neighboring
      islands.
AB  - Diversification of freshwater fishes on islands is considered unlikely because
      the traits that enable successful colonization-specifically, broad salinity
      tolerances and the potential for oceanic dispersal-may also constrain post
      colonization genetic differentiation. Some secondary freshwater fish, however,
      exhibit pronounced genetic differentiation and geographic structure on islands,
      whereas others do not. It is unclear what conditions give rise to contrasting
      patterns of differentiation because few comparative reconstructions of population
      history have been carried out for insular freshwater fishes. In this study, we
      examined the phylogeography of Hart's killifish (Rivulus hartii) across Trinidad,
      with reference to neighboring islands and northern South America, to test
      hypotheses of colonization and differentiation derived from comparable work on co
      occurring guppies (Poecilia reticulata). Geographic patterns of mitochondrial DNA
      haplotype variation and microsatellite genotype variation provide evidence of
      genetic differentiation of R. hartii among islands and across Trinidad. Our
      findings are largely consistent with patterns of geographically structured
      ancestry and admixture found in Trinidadian guppies, which suggests that both
      species share a history of colonization and differentiation and that post
      colonization diversification may be more common among members of insular
      freshwater fish assemblages than has been previously thought.

PMID- 21199029
TI  - Looking at both sides of the invasion: patterns of colonization in the violet
      tunicate Botrylloides violaceus.
AB  - Understanding the ecological and evolutionary forces that shape the genetic
      structure of invasive populations and facilitate their expansion across a large
      spectrum of environments is critical for the prediction of spread and management
      of ongoing invasions. Here, we study the dynamics of postestablishment
      colonization in the colonial ascidian Botrylloides violaceus, a notorious marine
      invader. After its initial introduction from the Northwest Pacific, B. violaceus
      spread rapidly along the Pacific and Atlantic coasts of North America, impacting
      both aquaculture facilities and natural ecosystems. We compare genetic diversity
      and patterns of gene flow among 25 populations (N=679) from the West and East
      coasts, and evaluate the contribution of sexual vs. asexual reproduction to this
      species' invasion success using data from the mitochondrial cytochrome c oxidase
      subunit I (COI) gene and 13 nuclear polymorphic microsatellite loci. Our results
      reveal contrasting patterns of spread in the coastal waters of North America.
      While the West coast was colonized by noncontiguous (long-distance) dispersal,
      the East coast invasion appears to have occurred through contiguous (stepping
      stone) spread. Molecular data further indicate that although dispersal in
      colonial ascidians is predominantly achieved through sexually produced
      propagules, aquaculture practices such as high-pressure washing can facilitate
      fragmentation and potentially exacerbate infestations and spread via asexual
      propagules. The results presented here suggest that caution should be used
      against the general assumption that all invasions, even within a single species,
      exhibit similar patterns of colonization, as highly contrasting dynamics may
      transpire in different invaded ranges.

PMID- 21199030
TI  - Pursuing glacier retreat: genetic structure of a rapidly expanding Larix decidua
      population.
AB  - One of the greatest threats to the long-term viability of migrating plant species
      is the loss of genetic diversity due to founder effects. Populations can expand
      as a response to climate change, but it is uncertain if long-lived plant species
      can maintain sufficient genetic diversity at the leading edge of migrating
      populations. This study uses an expanding Larix decidua population investigated
      along a chronosequence at landscape (350 ha) and local (0.8 ha) scales to test
      whether accelerated migration as a result of climate warming has the potential to
      intensify genetic erosion. Nine SSR markers revealed similar genetic diversity
      among eight sub-populations along the chronosequence (overall H(e) = 0.73;
      SE=0.04). Sub-populations were not genetically differentiated and all sampled
      individuals (N=730) formed one major genetic cluster indicating homogenizing gene
      flow despite spatial genetic structure (SGS) up to 80 m. At the local scale,
      individuals at the leading edge [early successional sub-population (ESSP), N
      =140] and a sub-population at equilibrium [late successional sub-population
      (LSSP), N = 290] revealed high genetic diversity in largest-sized cohorts. SGS
      among juveniles occurred up to 30 m in LSSP but there was no structure in ESSP.
      Accordingly, a maximum likelihood paternity assignment revealed local gene
      dispersal in LSSP (2-48 m) and intermediate-to-long distance dispersal into ESSP
      (115-3132 m). The findings indicate intensive mixing of the genes in this
      expanding population instead of founder effects and support the view that genetic
      diversity can be maintained in a long-lived species during rapid population
      expansion driven by climate warming.

PMID- 21199031
TI  - Transcriptomic responses to salinity stress in invasive and native blue mussels
      (genus Mytilus).
AB  - The invasive marine mussel Mytilus galloprovincialis has displaced the native
      congener Mytilus trossulus from central and southern California, but the native
      species remains dominant at more northerly sites that have high levels of
      freshwater input. To determine the extent to which interspecific differences in
      physiological tolerance to low salinity might explain limits to the invasive
      species' biogeography, we used an oligonucleotide microarray to compare the
      transcriptional responses of these two species to an acute decrease in salinity.
      Among 6777 genes on the microarray, 117 genes showed significant changes that
      were similar between species, and 12 genes showed significant species-specific
      responses to salinity stress. Osmoregulation and cell cycle control were
      important aspects of the shared transcriptomic response to salinity stress,
      whereas the genes with species-specific expression patterns were involved in mRNA
      splicing, polyamine synthesis, exocytosis, translation, cell adhesion, and cell
      signalling. Forty-five genes that changed expression significantly during
      salinity stress also changed expression during heat stress, but the direction of
      change in expression was typically opposite for the two forms of stress. These
      results (i) provide insights into the role of changes in gene expression in
      establishing physiological tolerance to acute decreases in salinity, and (ii)
      indicate that transcriptomic differences between M. galloprovincialis and M.
      trossulus in response to salinity stress are subtle and involve only a minor
      fraction of the overall suite of gene regulatory responses.

PMID- 21199032
TI  - Geographic variation of the major histocompatibility complex in Eastern Atlantic
      grey seals (Halichoerus grypus).
AB  - Pathogen-driven balancing selection maintains high genetic diversity in many
      vertebrates, particularly in the major histocompatibility complex (MHC) immune
      system gene family, which is often associated with disease susceptibility. In
      large natural populations where subpopulations face different pathogen pressures,
      the MHC should show greater genetic differentiation within a species than neutral
      markers. We examined genetic diversity at the MHC-DQB locus and nine putatively
      neutral microsatellite markers in grey seals (Halichoerus grypus) from eight
      United Kingdom (UK) colonies, the Faeroe Islands and Sable Island, Canada. Five
      DQB alleles were identified in grey seals, which varied in prevalence across the
      grey seal range. Among the seal colonies, significant differences in DQB allele
      and haplotype frequencies and in average DQB heterozygosity were observed.
      Additionally, the DQB gene exhibited greater differentiation among colonies
      compared with neutral markers, yet a weaker pattern of isolation by distance
      (IBD). After correcting for the underlying IBD pattern, subpopulations breeding
      in similar habitats were more similar to one another in DQB allele frequencies
      than populations breeding in different habitats, but the same did not hold true
      for microsatellites, suggesting that habitat-specific pathogen pressure
      influences MHC evolution. Overall, the data are consistent with selection at MHC
      DQB loci in grey seals with both varying selective pressures and geographic
      population structure appearing to influence the DQB genetic composition of
      breeding colonies.

PMID- 21199033
TI  - Variation in social organization influences the opportunity for sexual selection
      in a social lizard.
AB  - Social monogamy has traditionally been suggested to be maintained because of weak
      sexual selection on male partner acquisition. However, the ubiquitous incidence
      of extra-pair paternity suggests that sexual selection can be strong in
      monogamous systems, although studies partitioning variance in male reproductive
      success have come to mixed conclusions. Here, we use detailed field data to
      examine variance in male reproductive success and its implications for the
      maintenance of sociality in a population of the socially monogamous lizard
      Egernia whitii. We show that both within-pair and, to a lesser extent, extra-pair
      partner acquisition contribute to the variance in male reproductive success,
      resulting in considerable opportunity for sexual selection. Despite this, levels
      of multiple mating are lower in Egernia compared to other reptiles, suggesting
      that male partner acquisition is constrained. We suggest that this constraint may
      be a result of strong territoriality combined with sexual conflict over multiple
      mating generated by costs of extra-pair paternity to females as a result of
      facultative male care. This has the potential to limit sexual selection by
      reducing variance in male reproductive success and therefore contribute to the
      maintenance of complex social organization.

PMID- 21199034
TI  - Phylogeography of a pan-Atlantic abyssal protobranch bivalve: implications for
      evolution in the Deep Atlantic.
AB  - The deep sea is a vast and essentially continuous environment with few obvious
      barriers to gene flow. How populations diverge and new species form in this
      remote ecosystem is poorly understood. Phylogeographical analyses have begun to
      provide some insight into evolutionary processes at bathyal depths (<3000 m), but
      much less is known about evolution in the more extensive abyssal regions (>3000
      m). Here, we quantify geographical and bathymetric patterns of genetic variation
      (16S rRNA mitochondrial gene) in the protobranch bivalve Ledella ultima, which is
      one of the most abundant abyssal protobranchs in the Atlantic with a broad
      bathymetric and geographical distribution. We found virtually no genetic
      divergence within basins and only modest divergence among eight Atlantic basins.
      Levels of population divergence among basins were related to geographical
      distance and were greater in the South Atlantic than in the North Atlantic. Ocean
      wide patterns of genetic variation indicate basin-wide divergence that exceeds
      what others have found for abyssal organisms, but considerably less than bathyal
      protobranchs across similar geographical scales. Populations on either side of
      the Mid-Atlantic Ridge in the North Atlantic differed, suggesting the Ridge might
      impede gene flow at abyssal depths. Our results indicate that abyssal populations
      might be quite large (cosmopolitan), exhibit only modest genetic structure and
      probably provide little potential for the formation of new species.

PMID- 21199035
TI  - Are low but statistically significant levels of genetic differentiation in marine
      fishes 'biologically meaningful'? A case study of coastal Atlantic cod.
AB  - A key question in many genetic studies on marine organisms is how to interpret a
      low but statistically significant level of genetic differentiation. Do such
      observations reflect a real phenomenon, or are they caused by confounding factors
      such as unrepresentative sampling or selective forces acting on the marker loci?
      Further, are low levels of differentiation biologically trivial, or can they
      represent a meaningful and perhaps important finding? We explored these issues in
      an empirical study on coastal Atlantic cod, combining temporally replicated
      genetic samples over a 10-year period with an extensive capture-mark-recapture
      study of individual mobility and population size. The genetic analyses revealed a
      pattern of differentiation between the inner part of the fjord and the open
      skerries area at the fjord entrance. Overall, genetic differentiation was weak
      (average F(ST)  = 0.0037), but nevertheless highly statistical significant and
      did not depend on particular loci that could be subject to selection. This
      spatial component dominated over temporal change, and temporal replicates
      clustered together throughout the 10-year period. Consistent with genetic
      results, the majority of the recaptured fish were found close to the point of
      release, with <1% of recaptured individuals dispersing between the inner fjord
      and outer skerries. We conclude that low levels of genetic differentiation in
      this marine fish can indeed be biologically meaningful, corresponding to
      separate, temporally persistent, local populations. We estimated the genetically
      effective sizes (N(e) ) of the two coastal cod populations to 198 and 542 and
      found a N(e) /N (spawner) ratio of 0.14.

PMID- 21199036
TI  - Diversity and infection prevalence of endosymbionts in natural populations of the
      chestnut weevil: relevance of local climate and host plants.
AB  - Many insects are ubiquitously associated with multiple endosymbionts, whose
      infection patterns often exhibit spatial and temporal variations. How such
      endosymbiont variations are relevant to local adaptation of the host organisms is
      of ecological interest. Here, we report a comprehensive survey of endosymbionts
      in natural populations of the chestnut weevil Curculio sikkimensis, whose larvae
      are notorious pests of cultivated chestnuts and also infest acorns of various
      wild oaks. From 968 insects representing 55 localities across the Japanese
      Archipelago and originating from 10 host plant species, we identified six
      distinct endosymbiont lineages, namely Curculioniphilus, Sodalis, Serratia,
      Wolbachia, Rickettsia and Spiroplasma, at different infection frequencies (96.7%,
      12.8%, 82.3%, 82.5%, 28.2% and 6.8%, respectively) and with different
      geographical distribution patterns. Multiple endosymbiont infections were very
      common; 3.18+/-0.61 (ranging from 1.74 to 5.50) endosymbionts per insect on
      average in each of the local populations. Five pairs of endosymbionts
      (Curculioniphilus-Serratia, Curculioniphilus-Wolbachia, Sodalis-Rickettsia,
      Wolbachia-Rickettsia and Rickettsia-Spiroplasma) co-infected the same host
      individuals more frequently than expected, while infections with Serratia and
      Wolbachia were negatively correlated to each other. Infection frequencies of the
      endosymbionts were significantly correlated with climatic and ecological factors:
      for example, higher Sodalis, Wolbachia and Rickettsia infections at localities of
      higher temperature; lower Wolbachia and Rickettsia infections at localities of
      greater snowfall; and higher Curculioniphilus, Sodalis, Serratia, Wolbachia and
      Rickettsia infections on acorns than on chestnuts. These patterns are discussed
      in relation to potential host-endosymbiont co-evolution via local adaptation
      across geographical populations.

PMID- 21199037
TI  - One haploid parent contributes 100% of the gene pool for a widespread species in
      northwest North America.
AB  - The monoicous peatmoss Sphagnum subnitens has a tripartite distribution that
      includes disjunct population systems in Europe (including the Azores),
      northwestern North America and New Zealand. Regional genetic diversity was
      highest in European S. subnitens but in northwestern North America, a single
      microsatellite-based multilocus haploid genotype was detected across 16 sites
      ranging from Coos County, Oregon, to Kavalga Island in the Western Aleutians (a
      distance of some 4115 km). Two multilocus haploid genotypes were detected across
      14 sites on South Island, New Zealand. The microsatellite-based regional genetic
      diversity detected in New Zealand and North American S. subnitens is the lowest
      reported for any Sphagnum. The low genetic diversity detected in both of these
      regions most likely resulted from a founder event associated with vegetative
      propagation and complete selfing, with one founding haploid plant in northwest
      North America and two in New Zealand. Thus, one plant appears to have contributed
      100% of the gene pool for the population systems of S. subnitens occurring in
      northwest North America, and this is arguably the most genetically uniform group
      of plants having a widespread distribution yet detected. Although having a
      distribution spanning 12.5 degrees  of latitude and 56 degrees  of longitude,
      there was no evidence of any genetic diversification in S. subnitens in northwest
      North America. No genetic structure was detected among the three regions, and it
      appears that European plants of S. subnitens provided the source for New Zealand
      and northwest North American populations.

PMID- 21199038
TI  - Relationships between polysomnographic variables, parameters of glucose
      metabolism, and serum androgens in obese adolescents with polycystic ovarian
      syndrome.
AB  - The aim of this study was to compare polysomnographic variables of obese
      adolescents with polycystic ovarian syndrome (PCOS) to those of healthy controls
      and to analyse whether polysomnographic variables correlate to parameters of body
      weight/body composition, to serum androgens and to parameters of glucose
      metabolism. Thirty-one obese adolescents with PCOS (15.0 years +/- 1.0, body mass
      index 32.7 kg per m(2) +/- 6.2) and 19 healthy obese adolescents without PCOS
      (15.2 years +/- 1.1, body mass index 32.4 kg per m(2) +/- 4.0) underwent
      polysomnography to compare apnoea index, hypopnoea index, apnoea-hypopnoea index,
      the absolute number of obstructive apnoeas, percentage sleep Stages 1, 2, 3 and 4
      of non-rapid eye movement (NREM) sleep, percentage of REM sleep, TIB, total sleep
      time (TST), sleep-onset latency, total wake time (TWT), wakefulness after sleep
      onset (WASO) and sleep efficiency. Furthermore, we correlated polysomnographic
      variables to parameters of body weight/body composition, to serum androgens and
      to parameters of glucose metabolism. We found no differences between the two
      groups concerning the respiratory indices, percentage sleep Stages 2, 3 and 4 of
      NREM sleep, TIB and sleep-onset latency. The girls with PCOS differed
      significantly from the controls regarding TST, WASO, TWT, sleep efficiency,
      percentage Stage 1 of NREM sleep and percentage of REM sleep. We found a weak
      significant correlation between insulin resistance and apnoea index and between
      insulin resistance and apnoea-hypopnoea index. Concerning the respiratory
      variables, adolescents with PCOS do not seem to differ from healthy controls;
      however, there seem to be differences concerning sleep architecture.

PMID- 21199039
TI  - Association of sleep duration with weight and weight gain: a prospective follow
      up study.
AB  - The objective of this study was to examine the associations of sleep duration
      with subsequent weight and major weight gain in women and men during a follow-up
      period of 5-7years. The data were derived from the Helsinki Health Study cohort
      mail questionnaire surveys among 40-60-year-old employees of the City of
      Helsinki, Finland. At baseline in 2000-2002, 8960 people responded to the survey
      (80% women, response rate 67%). The follow-up survey was conducted in 2007 among
      all respondents to the baseline survey (n=7332, response rate 83%). Sleep
      duration (5h or less up to 10h or more) and weight and weight gain of at least
      5kg were based on self-reports. Analyses of variance and logistic regression
      analyses were used to examine the associations between sleep duration and weight,
      as well as major weight gain. Short sleep duration was associated with major
      weight gain [odds ratio (OR) 1.52; 95% confidence interval (CI) 1.08, 2.14]
      during the follow-up. Adjusting for several covariates had only minor effects on
      that association. Long sleep duration was associated with major weight gain after
      adjusting for age (OR 1.35; 95% CI 1.00-1.81). No associations were found among
      men. Sleep duration was associated with major weight gain among middle-aged
      employed women. Short sleep may be a risk factor for subsequent weight gain.

PMID- 21199040
TI  - Variability in genetic syndromes: Some lessons from history.

PMID- 21199042
TI  - Associations and costs of parental symptoms of psychiatric distress in a multi
      diagnosis group of children with special needs.
AB  - BACKGROUND: Families supporting children with complex needs are significantly
      more distressed and economically disadvantaged than families of children without
      disability and delay. What is not known is the associations and costs of parental
      psychiatric distress within a multi-diagnosis group of special needs children.
      METHODS: In this cross-sectional survey, families were identified from the
      Children's Treatment Network. Families were eligible if the child was aged 0-19
      years, resided in Simcoe/York, and if there were multiple family needs (n = 429).
      RESULTS: Some 42% of surveyed parents exhibited symptoms (mild to severe) of
      psychiatric distress. The presence of these symptoms was associated with reports
      of poorer social support, family dysfunction, greater adverse impact of the
      child's situation on the family, poorer child behaviour, unfavourable parenting
      styles and poorer child psychosocial functioning. The severity of the child's
      physical dysfunction was not related to parents/guardians most knowledgeable
      symptoms of psychiatric distress. Total parent costs were higher and children's
      uses of primary care services were higher in parents with symptoms of psychiatric
      distress. CONCLUSION: Parent symptoms of psychiatric distress are a significant
      societal concern in families with complex needs children. Children's
      rehabilitation efforts need to incorporate parental mental health assessment and
      treatment into existing programmes. This could lead to decreases in direct and
      indirect healthcare utilisation costs.

PMID- 21199043
TI  - Is the Autism Treatment Evaluation Checklist a useful tool for monitoring
      progress in children with autism spectrum disorders?
AB  - BACKGROUND: There are few well validated brief measures that can be used to
      assess the general progress of young children with autism spectrum disorders
      (ASD) over time. In the present study, the Autism Treatment Evaluation Checklist
      (ATEC) was used as part of a comprehensive assessment battery to monitor the
      progress of 22 school-aged children with ASD who had previously taken part in
      intensive home- or school-based intervention programmes in their pre-school
      years. METHODS: Parents completed the ATEC when the children were on average 5.5
      years and then again 5-6 years later (mean age 10.4 years). Standardised measures
      were also used to assess cognitive, language and adaptive behaviour skills and
      severity of autism symptoms over the same period. RESULTS: The ATEC had high
      internal consistency at both time points. ATEC total and sub-scale scores
      remained relatively stable over time and were highly and significantly correlated
      with cognitive, language and adaptive behaviour skills and severity of autism
      symptoms at both assessment points. Initial ATEC total scores predicted 64% of
      the variance in scores at the subsequent follow-up. However, there was also
      considerable variation in the patterns of scores shown by individual children
      over time. CONCLUSIONS: This study provides some preliminary evidence of the
      ATEC's potential value for monitoring progress of children with ASD over time.
      Its advantages and limitations are discussed in the context of the need
      systematically to monitor the progress of children with ASD over time or in
      response to intervention.

PMID- 21199044
TI  - Neighbourhood deprivation, health inequalities and service access by adults with
      intellectual disabilities: a cross-sectional study.
AB  - BACKGROUND: Adults with intellectual disabilities (IDs) experience health
      inequalities and are more likely to live in deprived areas. The aim of this study
      was to determine whether the extent of deprivation of the area a person lives in
      affects their access to services, hence contributing to health inequalities.
      METHOD: A cross-sectional study design was used. Interviews were conducted with
      all adults with IDs within a defined location (n = 1023), and their medical
      records were reviewed. The extent of area deprivation was defined by postcode,
      using Carstairs scores. RESULTS: Area deprivation did not influence access to
      social supports, daytime primary health-care services or hospital admissions, but
      people in more deprived areas made less use of secondary outpatient health care
      [first contacts (P = 0.0007); follow-ups (P = 0.0002)], and more use of accident
      and emergency care (P = 0.02). Women in more deprived areas were more likely to
      have had a cervical smear; there was little association with other health
      promotion uptake. Area deprivation was not associated with access to paid
      employment, daytime occupation, nor respite care. These results were essentially
      unchanged after adjusting for type of accommodation and level of ability.
      CONCLUSIONS: Deprivation may not contribute to health inequality in the
      population with IDs in the same way as in the general population. Focusing health
      promotion initiatives within areas of greatest deprivation would be predicted to
      introduce a further access inequality.

PMID- 21199045
TI  - Training emotional intelligence related to treatment skills of staff working with
      clients with intellectual disabilities and challenging behaviour.
AB  - BACKGROUND: Staff working with clients with intellectual disabilities (ID) who
      display challenging behaviour may contribute to the continuation of this
      behaviour, because it causes emotional reactions such as anxiety, anger and
      annoyance, which may prohibit adequate response behaviour. To enhance staff
      behaviour and treatment skills a training that aimed at improving emotional
      intelligence (EQ) was developed. AIM: The goal of this study was to assess
      whether an EQ training in combination with a video-feedback training programme
      improves emotional intelligence of staff working with clients with ID and
      challenging behaviour. METHODS: Participants were 60 staff members working with
      individuals with ID and challenging behaviour. Thirty-four staff members
      participated in a 4-month training programme and 26 constituted the control
      group. A pretest-posttest control group design was used. Effectiveness was
      assessed by using the Dutch version of the Bar-On EQ-i and the judgments of
      experts on emotional intelligence. RESULTS: Emotional intelligence of the
      experimental group changed significantly more than that of the control group.
      Judgments of experts on emotional intelligence indicated that the change of
      emotional intelligence of the experimental group improved positively.
      CONCLUSIONS: The positive effect of the training programme on emotional
      intelligence is consistent with previous research on emotional intelligence and
      suggests that emotional intelligence of staff working with clients with ID and
      challenging behaviour can be influenced by training.

PMID- 21199046
TI  - The relationship between specific cognitive impairment and behaviour in Prader
      Willi syndrome.
AB  - BACKGROUND: Individuals with Prader-Willi syndrome (PWS) have been shown to
      demonstrate a particular cognitive deficit in attention switching and high levels
      of preference for routine and temper outbursts. This study assesses whether a
      specific pathway between a cognitive deficit and behaviour via environmental
      interaction can exist in individuals with PWS. METHODS: Four individuals with PWS
      participated in a series of three single-case experiments including laboratory
      based and natural environment designs. Cognitive (computer-based) challenges
      placed varying demands on attention switching or controlled for the cognitive
      demands of the tasks while placing no demands on switching. Unexpected changes to
      routines or expectations were presented in controlled games, or imposed on
      participants' natural environments and compared with control conditions during
      which no unexpected changes occurred. Behaviour was observed and heart rate was
      measured. RESULTS: Participants showed significantly increased temper outburst
      related behaviours during cognitive challenges that placed demands on attention
      switching, relative to the control cognitive challenges. Participants showed
      significantly increased temper outburst related behaviours when unexpected
      changes occurred in an experimental or the natural environment compared with when
      no changes occurred. CONCLUSIONS: Difficult behaviours that could be triggered
      reliably in an individual by a specific cognitive demand could also be triggered
      via manipulation of the environment. Results suggest that a directional
      relationship between a specific cognitive deficit and behaviour, via
      environmental interaction, can exist in individuals with PWS.

PMID- 21199047
TI  - A pilot study of social competence group training for adolescents with borderline
      intellectual functioning and emotional and behavioural problems (SCT-ABI).
AB  - BACKGROUND: Emotional and behavioural problems as well as a lack of social
      competence are common in adolescents with borderline intellectual functioning and
      impair their social and vocational integration. Group interventions specifically
      developed for this target group are scarce and controlled evaluation studies are
      absent. METHODS: A cognitive-behavioural group training (Social Competence
      Training for Adolescents with Borderline Intelligence) was developed and its
      effectiveness was examined in students attending special vocational schools. A
      total of 77 adolescents with borderline intelligence were randomised either to
      the intervention (n=40) or to the control group (n=37). Outcome measures at post
      treatment and at a 6-month follow-up comprised self-reports, caregiver reports
      and behavioural observations. RESULTS: The adolescents in the intervention group
      showed temporally stable improvement in their social competence, especially in
      social problem solving (F=17.6, P<0.001) and attainment of individual behavioural
      goals in everyday life (self-reports: F=15.9, P<0.001; caregiver reports: F=87.9,
      P<0.001). Effects of the intervention on other outcomes such as problem-solving
      competence and skills performed in standardised role plays were weak or absent.
      CONCLUSIONS: Social Competence Training for Adolescents with Borderline
      Intelligence is a promising treatment for adolescents with borderline
      intellectual functioning and associated emotional/behavioural symptoms. Further
      studies examining long-term effects on the participants' social and vocational
      integration are needed.

PMID- 21199048
TI  - Stereotyped behaviour in children with autism and intellectual disability: an
      examination of the executive dysfunction hypothesis.
AB  - BACKGROUND: Increasing attention has been paid to the executive dysfunction
      hypothesis argued to underpin stereotyped behaviour in autism. The aim of this
      study is to investigate one component of this model, that stereotyped behaviours
      are related to impaired generativity and compromised behavioural inhibition, by
      examining whether episodes of these behaviours terminate naturally without
      external intervention. METHODS: Using a naturalistic observational methodology
      the stereotyped behaviours of six participants with autism were recorded in real
      time over periods ranging from 3.59 to 9.20 h. Data were also recorded for
      teaching staff interactions with participants and environmental settings (one-to
      one, group and freetime). RESULTS: In comparison with one-to-one settings
      stereotyped behaviours were more frequent when participants were in freetime
      settings with the exception of one participant. For the termination of
      stereotyped behaviours these behaviours stopped with no ongoing physical or
      verbal adult contact being evident for a median of 73.25% of the time.
      Additionally, for a median of 89.40% of the time stereotyped behaviour stopped
      without the initiation of adult contact. DISCUSSION: The termination of bouts of
      stereotyped behaviour was frequently not associated with any adult contact and
      thus this form of external intervention. This finding warrants explanation by
      extending the hypothesis that compromised impaired generativity and behavioural
      inhibition offers a complete explanation of stereotyped behaviours.

PMID- 21199049
TI  - Prevalence, phenomenology, aetiology and predictors of challenging behaviour in
      Smith-Magenis syndrome.
AB  - BACKGROUND: The prevalence, phenomenology aetiology and correlates of four forms
      of challenging behaviour in 32 children and adults with Smith-Magenis syndrome
      (SMS) were investigated. METHODS: Cognitive assessments, questionnaires and semi
      structured interviews were used to gather data on intellectual disability, verbal
      and physical aggression, destructive behaviour and self-injury and on
      characteristics known to be associated with aggression. RESULTS: Aggression in
      SMS was more prevalent (87%), but not more severe than aggression in contrast
      groups. Aggressive behaviour was more frequently associated with environmental
      contingencies (e.g. attention, escape and access to tangibles) than self-injury
      and destructive behaviours. Severity of challenging behaviours was associated
      with high impulsivity. CONCLUSION: Aggression is seen in the majority of people
      with SMS. Results suggest that behavioural disinhibition and operant social
      reinforcement are associated with the manifestation of aggression.

PMID- 21199050
TI  - Behavioural and emotional problems in people with severe and profound
      intellectual disability.
AB  - BACKGROUND: People with severe and profound levels of intellectual disability
      (ID) are frequently examined as a single group in research. However, these two
      groups may be significantly different, particularly in the area of emotional and
      behavioural difficulties. METHOD: The Developmental Behaviour Checklist (DBC) was
      completed by parents and caregivers of 107 people with severe ID and 22 people
      with profound ID at four time periods across 12 years. Regression analyses were
      used to examine trends in sub-scale scores across time and groups. RESULTS:
      Significant differences between the groups of people with severe and profound ID
      were found. People with profound ID had significantly lower scores across all sub
      scales except Social Relating. This was usually related to fewer items being
      selected as present for people with profound ID, as opposed to the scores being
      attributable to lower item severity scores. CONCLUSIONS: There are significant
      differences between groups of people with severe and profound ID in scores on the
      DBC, indicating differences in behavioural and emotional problems. Caution should
      be exercised by researchers treating these two disparate groups as a single
      group, and by practitioners translating such findings into practice.

PMID- 21199051
TI  - Abstracts of the XVIIth International Congress of Neuropathology (ICN 2010).
      Salzburg, Austria. September 11-15, 2010.

PMID- 21199052
TI  - Perivascular fibrosis in multiple sclerosis lesions.

PMID- 21199053
TI  - Diagnosis and management of urinary tract infection in children.
AB  - A young child presents to their primary health provider with fever and
      irritability. How likely is a urinary tract infection? How should a urine sample
      be collected? How accurate are urinary dipsticks and microscopy compared with
      culture for the diagnosis? What route and type of antibiotics should be used?
      What imaging is indicated? Diagnosing and treating children with urinary tract
      infection presents many questions. This review summarises the most relevant
      recent primary studies, systematic reviews and guidelines.

PMID- 21199054
TI  - The Western Pacific Regional Child Survival Strategy: progress and challenges in
      implementation.
AB  - The Regional Child Survival Strategy (RCSS) was launched by the World Health
      Organization and United Nations Children's Fund in 2006. This initially involved
      the six highest mortality burden countries in the region (Cambodia, China, Laos
      PDR, Papua New Guinea, Philippines and Vietnam). This paper aimed to describe the
      experiences of countries in the region in adopting and implementing the RCSS, and
      to identify factors that promote and impede progress. Child mortality has fallen
      substantially since 1990, and the region as a whole is on track to achieve the
      Millennium Development Goal 4 (MDG-4) targets. Some countries have made slower
      progress and are struggling. There is an urgent need to support countries that
      have, until now, not been included in the RCSS, particularly smaller Pacific
      Island nations, and to provide greater support to the poorest countries if MDG-4
      targets for the region are to be achieved.

PMID- 21199055
TI  - The impact of perinatal urinoma formation on renal function: our experience and
      review of the literature.
AB  - INTRODUCTION: A urinoma is a fluid mass consisting of extravasated urine in the
      perirenal space. Its impact on renal function was analysed. METHODS: All cases of
      prenatal and neonatal urinoma reported in the literature were analysed as well as
      two cases recently observed in our department. RESULTS: A review of all
      prenatally diagnosed urinomas revealed 25 cases, for a total of 30 renal units.
      The cause of obstruction was: lower urinary tract (LUT) obstruction in 16 cases
      (62.5%), upper urinary tract (UUT) obstruction in seven cases (29.5%) and unknown
      in two cases (8%). A preserved renal function was found in only 30% of all cases.
      Furthermore, prognosis for renal function was better in posterior urethral valve
      (PUV) patients than in uretero-pelvic junction obstruction (UPJO) patients. In
      addition, we analysed 35 published cases of urinoma with a neonatal onset,
      without prenatal diagnosis, and secondary to LUT obstruction in 27 cases (77%),
      UUT obstruction in seven cases (20%), while the underlying cause was unknown in
      one cases (3%). A preserved renal function was observed in 84% of cases with UUT
      obstruction and in 80% of cases presenting a LUT obstruction. CONCLUSIONS:
      Prognosis concerning renal function seems to be mainly related to two factors:
      age at presentation and underlying diagnosis. Decompression of the urinary tract
      by urine extravasation produces the best results in terms of preservation of the
      renal function in LUT obstruction (75% in prenatal and 84% in postnatal cases);
      UUT obstruction however is associated with a good prognosis in the neonatal
      period (80% of preserved renal function) but with a severe impairment (only 20%
      of preserved renal function) in prenatally detected cases.

PMID- 21199056
TI  - Update on attention deficit hyperactivity disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) is now the most frequent
      diagnosis in children seen by Australian general paediatricians. It is a
      heterogeneous neurodevelopmental disorder and is usually accompanied by one or
      more co-morbid developmental and/or mental health conditions. In addition to
      daily symptoms, which often impair quality of life, ADHD can compromise
      educational and social development for the individual, and impact on families,
      schools and the broader community. Draft revised National Health and Medical
      Research Council Guidelines on ADHD were published in November 2009. This
      comprehensive document discusses the evidence in relation to many aspects of
      ADHD, which inform the large number of practice recommendations. Although there
      is an enormous literature on the causes, neurobiology and management of ADHD,
      there is still much to be learned particularly in relation to early intervention,
      behavioural therapies and factors influencing long-term outcomes.

PMID- 21199057
TI  - Streptococcus pneumoniae sepsis in the newborn.
AB  - BACKGROUND: Streptococcus pneumoniae (SP) is an uncommon cause of neonatal
      sepsis. AIMS: To report on the spectrum of morbidity associated with SP
      infections in the neonatal period. METHODS: A case series of SP infection in the
      neonatal period was studied. Maternal and neonatal outcomes were noted. RESULTS:
      Four cases of neonatal SP infection are reported, one of which was due to a
      strain with reduced susceptibility to penicillin. All four cases had very early
      onset of severe clinical disease with bacteremia and pneumonia. In one case a
      retrospective diagnosis of meningitis was made as well. Maternal illness was a
      feature in one of these infants. CONCLUSIONS: Although less common now than in
      the pre-antibiotic era, Streptococcus pneumoniae remains a rare but important
      cause of neonatal sepsis and can mimic early onset Group B streptococcal sepsis.
      It is unclear whether current infant or adult pneumococcal immunisation programs
      might influence its incidence in the neonatal period. The potential for strains
      with reduced susceptibility to beta-lactam antibiotics to cause neonatal
      infection needs to be considered in relevant settings.

PMID- 21199058
TI  - Children of substance-using mothers: child health engagement and child protection
      outcomes.
AB  - AIM: Maternal substance use has been associated with a range of child risk
      factors. The study investigated the relationship between engagement with child
      health services and child protection outcomes for children of substance-using
      mothers. METHODS: The sample comprised 119 children of mothers who disclosed
      opiate, amphetamine or methadone use during a maternity admission between 2000
      and 2003. Statutory child protection agency and child health engagement
      information for the first 2 years of life was obtained. The relationship between
      type of maternal substance use, child health engagement and child protection
      outcomes was examined. RESULTS: Of study group infants, 72% were engaged with
      child health services during the first 2 years of life. Chi-squared analysis
      showed no significant relationship between child health engagement and child
      protection reports. Child health engagement was associated with decreased
      substantiated child protection notifications for children of methadone using
      mothers, but not for children of illicit substance users. CONCLUSIONS: Almost a
      quarter of identified children of substance-using mothers are not accessing
      standard child health services in their first 2 years of life. This study
      provides support for increased attention to the provision of child health
      services for children of methadone using mothers. Further research into effective
      intervention strategies for children of illicit substance-using mothers is
      indicated.

PMID- 21199059
TI  - Intrapleural urokinase versus surgical management of childhood empyema.
AB  - AIM: Empyema can be managed conservatively with intravenous antibiotics or
      invasively with a drain inserted under image guidance or via surgical evacuation.
      Both approaches are successful but comparisons of the method of drainage are few.
      This study compared clinical outcomes for empyema in previously well children
      from a single centre over a 12 year period. METHODS: A retrospective analysis of
      cases over 12 years from the Children's Hospital at Westmead in Sydney was
      undertaken. Ethics committee approval was obtained. RESULTS: Seventy two cases
      were identified from medical records, 12 cases were excluded and 60 cases
      remained. The mean age was 4.7+/-4.3 years and there was a slight male
      preponderance. Treatment was divided into surgical management with a large bore
      drain alone [n=25] and minimally invasive management with the use of a "pigtail
      catheter" and intrapleural fibrinolytic ["Urkoinase"][n=35]. At presentation the
      mean heart rate and respiratory rate were not statistically different. The median
      (range) number of doses of urokinase was 5.66 doses (1-12). More fluid was
      drained with the use of urokinase [594 ml (25-4575 ml) vs. 195 ml (10-1426 ml);
      p=0.006], but this did not influence the rate of resolution of fever or the
      length of hospital stay. A pathogen was isolated in 42.9% of the urokinase group
      and 68% of the surgical group which approached statistical significance
      [p=0.054]. CONCLUSIONS: Both large bore surgical drains and "pigtail catheter"
      drains with the instillation of urokinase lead to similarly favourable treatment
      outcomes. Either treatment could be recommended depending on local expertise and
      preferences.

PMID- 21199060
TI  - Cardiac cirrhosis and hepatocellular carcinoma in a 13-year-old treated with
      doxorubicin microbead transarterial chemoembolization.
AB  - Increasing numbers of children are surviving into adulthood following surgery to
      correct or palliate congenital heart disease. This surgery can occasionally
      result in long-standing elevated right heart pressures and chronic hepatic venous
      congestion leading to cardiac cirrhosis. We report the first paediatric case of
      hepatocellular carcinoma in the setting of cardiac cirrhosis. A 13-year-old girl
      developed inoperable hepatocellular carcinoma and was treated with transarterial
      embolization with lipiodol and doxorubicin eluting microbeads. Promoting
      awareness of this association, even in younger patients, will hopefully result in
      better surveillance and screening of hepatic complications in survivors of
      complex cardiac surgery.

PMID- 21199062
TI  - Persistence of acute rheumatic fever in a tertiary children's hospital.
AB  - AIM: To identify and describe all children admitted with acute rheumatic fever
      (ARF) to a tertiary paediatric hospital in Sydney over a 9-year period and to
      describe their demographic and clinical characteristics, management and short
      term outcomes. Delays in diagnosis, recurrence of ARF and use of secondary
      prophylaxis were also documented. METHODS: Retrospective review of medical
      records for children aged < 15 years admitted to the Children's Hospital at
      Westmead, Sydney, with ARF (International Classification of Diseases (ICD)-10
      classification I0.0-109.9) during 2000-2008. Only cases meeting the National
      Heart Foundation of Australia diagnostic criteria for ARF were included. RESULTS:
      Twenty-six children met the National Heart Foundation of Australia criteria for
      ARF. The median age was 11.5 years (range 5.8-14.6) and 15 (58%) were male. Ten
      (38%) identified as Pacific Islander, and 5 (19%) as Aboriginal and Torres Strait
      Islander (ATSI). Most (n= 20, 77%) lived in suburban Sydney, and 69% were
      classified in the two most disadvantaged quintiles on the Index of Relative
      Socioeconomic Disadvantage and Advantage. Four (15%) had Sydenham's chorea, and
      81% had carditis (mitral and/or aortic regurgitation). Six (23%) children had
      previous ARF. Antibiotic prophylaxis to prevent recurrent ARF was prescribed in
      all cases, but 50% received oral penicillin, rather than by intramuscular
      injection. Barriers to timely diagnosis were identified in 81%, including delayed
      presentation and delayed referral. CONCLUSION: Most children presenting to the
      hospital with ARF lived in disadvantaged areas of Sydney. Pacific Islander and
      Aboriginal and Torres Strait Islander children were over-represented. Mitigation
      of RHD requires early identification of ARF and appropriate delivery of secondary
      prophylaxis.

PMID- 21199061
TI  - Vascular catheter-related complications in newborns.
AB  - Babies in Neonatal Intensive Care Unit have more frequent invasive procedures
      such as heel prick samples for gases, bilirubin levels or if ventilated suction
      down the endotracheal tube is more frequent and still invasive. Central and
      peripheral vascular catheters are essential to serve many important functions for
      sick neonates. However, there is growing recognition of potential risks, such as
      infection, thrombosis, vasospasm, phlebitis, infiltration and so on, associated
      with their use. Based on current evidence, this paper reviews the common
      complications of vascular catheters and their corresponding preventive or
      treatment approaches in newborns.

PMID- 21199063
TI  - Antimicrobial responses in the male reproductive tract of lipopolysaccharide
      challenged rats.
AB  - PROBLEM: Innate immune machinery including the Toll-like receptors (TLRs) confers
      the first line of defense mechanisms to counter pathogenic microorganisms that
      enter the body. The male reproductive tract is vulnerable to infection and the
      role of TLRs and the antimicrobial responses that operate to counter infections
      in this organ system are poorly understood. METHOD OF STUDY: Caput and cauda
      epididymides, testes and seminal vesicles were collected at 0, 3, 6, 9, 12, 15
      and 24 h from rats injected intraperitoneally with a single dose of LPS. Plasma
      testosterone was measured using ELISA. Expression pattern of defensins and Spag11
      isoforms were analysed using RT-PCR. Immunohistochemical analyses was performed
      to determine SPAG11E protein expression following LPS treatment. RESULTS: We
      provide the first line of evidence that the male reproductive tract induces the
      expression of Sperm Associated Antigen 11 (Spag11) mRNA variants and defensins
      when challenged with lipopolysaccharide (LPS) with a concomitant increase in
      protein expression. However, there was an inverse relationship between induction
      of antimicrobial gene expression and plasma testosterone. An increase in the mRNA
      levels of proinflammatory cytokines was observed parallel to the induction of
      Spag11 variants and majority of defensin expression in the male reproductive
      tract. CONCLUSION: The increase in Spag11 and defensin mRNA in response to LPS
      administration demonstrates their importance in protecting the male reproductive
      tract during infection. Results of this study help to understand male
      reproductive tract innate immune defense mechanisms and to design novel peptide
      antibiotics to prevent sexually transmitted diseases.

PMID- 21199065
TI  - In vivo serial MR imaging evaluates neointimal hyperplasia inhibited by
      intravenously transfused endothelial progenitor cells in carotid artery injured
      mice.
AB  - PURPOSE: to study the feasibility of in vivo MR imaging in evaluation of
      endothelial progenitor cells (EPCs) on the progress of neointimal hyperplasia
      after carotid artery injury in mice. METHODS: fifteen Kunming mice were injured
      in left carotid artery by removal of endothelium with a flexible wire 7 days
      after splenectomy. EPCs were collected by in vitro culture of spleen-derived
      mouse mononuclear cells (MNCs) in endothelial basal medium. After artery injury,
      the mice received EPCs (n= 6), phosphate buffered solution (PBS) (n= 6), and DiI
      Ac-LDL labeled EPCs (n= 3) intravenously. In vivo serial MR imaging were
      performed at different time points after artery injury, and vessel-wall thickness
      and vessel-wall area at injury site were measured on MR imaging. RESULTS:
      transfused Dil-Ac-LDL-labeled EPCs were found at the injury site by
      histopathological analyses. Vessel wall of injured artery was observed and
      quantitatively analyzed with MR imaging. Vessel-wall thickness was .487 +/- .122
      mm in the non-EPCs transfusion group and .294 +/- .051 mm in the EPCs transfusion
      group 15 days after artery injury (P= .005). While vessel-wall area was .860 +/-
      .182 mm(2) in the non-EPCs transfusion group and .468 +/- .141 mm(2) in the EPCs
      transfusion group 15 days after artery injury (P= .002). Therefore, the
      neointimal hyperplasia of injured artery in the EPCs transfusion group was lesser
      than that in the non-EPCs transfusion group. CONCLUSION: neointimal hyperplasia
      can be reduced by intravenous transfusion of EPCs and analyzed on in vivo MR
      imaging after vascular injury.

PMID- 21199064
TI  - Methodological issues in sampling the local immune system of the female genital
      tract in the context of HIV prevention trials.
AB  - The spread of HIV continues unabated in the most vulnerable populations of the
      world. HIV prevention methods, such as a vaginal microbicide, a mucosal vaccine,
      pre-exposure prophylaxis or a vaccine, are urgently needed in the fight against
      new infections. We must make a commitment to supporting innovative research and
      product design, so that one or more of these products provide a halt to the
      spread of HIV. Above all, these products should be proven to be safe and not
      negatively disturb the local immune system in a way that facilitates or enhances
      heterosexual transmission of HIV. HIV specific and non specific cellular and
      humoral local vaginal immunity must be assessed in clinical trials when testing
      prevention products for safety or efficacy. A proven, well-documented and
      standardized sampling strategy will provide high quality data to be able to
      assess both safety and local immune responses. In this paper, we will discuss
      methods for vaginal immunology sampling in the context of clinical trials.

PMID- 21199068
TI  - Use of a validated reference tool to evaluate postoperative pain management
      through a quality-improvement program in a university hospital.
AB  - We audited the seven surgical departments of a university hospital before and
      after implementation of a program aiming to improve practices in postoperative
      pain management (POPM). Audits were conducted 2 years apart. During each
      evaluation, 10 medical charts from each surgical department (i.e., 70 charts)
      were analyzed for 9 quality criteria (five concerning anesthetist practices and
      four nursing practices). Two scores were calculated: one per department and the
      other per criteria. After the first audit, the seven departments received
      recommendations to improve their POPM. Targeted-training sessions were instituted
      for the three poorest performing departments (scores <4.5 out of 9 criteria).
      During the period between the two audits, all seven departments improved their
      scores; a statistically significant improvement was observed in five departments,
      including the three that had received targeted-training sessions. Moreover,
      overall scores for seven of the nine evaluated criteria improved, significantly
      for three criteria. Anesthetists significantly increased their overall score from
      2.5 +/- 0.8 to 3.7 +/- 0.6 out of 5 points (p=.018), while surgical nurses'
      overall score did not change significantly from 2.3 +/- 0.7 to 2.9 +/- 0.7 out of
      4 points (p=.128). In conclusion, using a standardized and validated instrument
      to evaluate POPM practices enables the identification of surgical departments
      requiring practice improvement and those quality criteria requiring
      reinforcement.

PMID- 21199069
TI  - Organizational and leadership perceptions assessment: opportunities and
      challenges using the Baldrige companion surveys.
AB  - Combining the use of employee perception surveys with sound analytical techniques
      and models is critical to capturing high quality data from which effective
      decisions can be made in complex healthcare settings. This study used the
      Baldrige Award companion surveys with an analysis of variance (ANOVA) framework
      to identify discordant perceptions of hospital staff and leadership in the areas
      of customer focus, knowledge management, and results that were significant at the
      0.05 and 0.01 levels. Senior leaders in the organization found the ANOVA
      framework helpful as they interpreted results from the Baldrige companion surveys
      and planned future improvement activities. During the execution of our study a
      number of difficulties and challenges arose that are not uncommon to survey
      administration in smaller settings, such as community hospitals, or in larger
      hospital settings with no research staff or research staff with relevant
      psychometric expertise. Our experience suggests that the Baldrige companion
      survey process would be enhanced by providing organizations with general guidance
      and protocols for optimal survey administration and data analysis. The purpose of
      this article is to outline the ANOVA model we used with the Baldrige companion
      surveys and to provide guidance related to the administration and analysis of
      these companion surveys for those that use them.

PMID- 21199070
TI  - An alternative to pay-for-performance: one health plan's approach to quality
      improvement.
AB  - To address concerns about the quality of care, health plans have used varying
      approaches to support quality improvement (QI). Pay-for-performance (P4P) is the
      most commonly used and discussed approach. P4P programs have many challenges in
      design and execution, particularly for Medicaid providers. In order to find an
      alternative to P4P, CareOregon--a nonprofit health plan serving Medicaid and
      Medicare enrollees--developed the Care Support and System Innovation (CSSI)
      Program. An evaluation was conducted to assess the overall affect of the CSSI
      Program in promoting comprehensive improvements in quality of care and the extent
      to which it has the potential to offer a viable alternative to P4P. The
      evaluation found that the CSSI Program successfully addressed many challenges
      inherent in P4P. The CSSI Program engaged providers, fostered a culture of QI
      within CareOregon's network, and provided practices with the opportunity to
      develop sustainable and innovative solutions to address quality concerns. Success
      of the program was attributed to CareOregon's focus on building relationships
      while providing technical assistance and responsive funding. While health outcome
      data were not available to assess impact on CareOregon's members, evaluation
      findings highlight the importance of collaboration in QI efforts, and suggest
      that the model has the potential to overcome many of the challenges faced by P4P.

PMID- 21199071
TI  - Emergency trauma care for severe injuries in a Moroccan region: conformance to
      French and World Health Organization standards.
AB  - In Morocco, injuries account for 11% of total burden of disease. Better
      organization of emergency care can improve the outcome of trauma patients. In
      Morocco, these services have been reorganized recently, but were never evaluated.
      The objective was to assess actual structure and processes of emergency trauma
      care in a Moroccan region. This comparative qualitative study was carried out in
      the region of Fez. The process and structure of contacting emergency care and
      prehospital emergency care were compared with the French 2002 standards.
      Emergency care at the University Teaching Hospital (UTH) was compared with World
      Health Organization 2005 Essential Trauma Care guidelines. Predefined care items
      were categorized as conforming to the standards or not. An emergency call center
      with a dedicated dial-up number has been established in the region since January
      2007. Compared with the standards, this center was not protected by any
      legislation and was run by interns only. The center was underutilized during
      triage to help transportation of severe trauma patients. At the prehospital care
      level, only 3 out of 15 ambulances were equipped with resuscitation equipment and
      were used rarely. Only one of the ambulance staff out of three was trained in
      required skills. At the UTH, emergency care equipment and staff was nearly
      adequate. This study identified several opportunities for improvement in
      organizing trauma care in Fez particularly at emergency call center and ambulance
      service. A quality assurance program would be useful to further identifying
      improvements in this system.

PMID- 21199072
TI  - Real-time assessment of nurse work environment and stress.
AB  - Ecological momentary assessment methods were used to examine real-time
      relationships between work environment factors and stress in a sample of 119
      registered nurses (RNs) in acute and critical care settings of three hospitals.
      The RNs carried handheld computers for 1 week of work shifts and were randomly
      surveyed within 90-min intervals to self-report work activity, perceived
      workload, and stress. Mixed effects linear regression analyses were completed to
      predict the stress score in the sample. The number of patients assigned
      significantly predicted stress; the greater the number of assigned patients, the
      higher the reported stress (p<.01). Age, gender, adult versus pediatric facility
      type, familiarity with patients, and proportion of direct care tasks were not
      significant predictors of stress. Further research is needed to link work
      environment factors and stress with errors among nurses.

PMID- 21199073
TI  - Developing medical record-based performance indicators to measure the quality of
      mental healthcare.
AB  - Recent attention has focused on validity and feasibility of different approaches
      to developing performance indicators for the purposes of quality improvement and
      value-based purchasing. This paper presents the methodology used to develop a
      comprehensive set of performance indicators that will be used for a national
      evaluation of the mental healthcare provided by the Veterans Health
      Administration. The paper report on the indicators' technical specifications and
      the United States Public Health System Task Force defined strength of supporting
      evidence. Indicators were reviewed iteratively for meaningfulness, utility,
      feasibility, and supporting evidence until a final set of measures of acceptable
      validity and feasibility was produced with technical specifications. Fifty-seven
      mental health performance indicators that use information from both the medical
      record and administrative data (hybrid indicators) and 31 administrative-data
      only indicators are presented. Of the 57 hybrid indicators, 13 indicators are
      supported by Agency for Healthcare Research and Quality grade I evidence, 5
      indicators are grade II, and 39 indicators are grade III. This paper describes
      the methodology used to develop 88 performance indicators of the quality of
      mental health and substance abuse treatment, and presents the technical
      specifications associated with each indicator.

PMID- 21199074
TI  - Improving patient transfer between the Intensive Care Unit and the
      Medical/Surgical floor of a 200-bed hospital in southern California.
AB  - This paper describes the work of a front-line team at a 200-bed hospital in
      southern California to improve the patient transfer process between the Intensive
      Care Unit (ICU) and the Medical/Surgical floors. Using a phased approach of
      assessing the problem, identifying opportunities, testing ideas, and then
      implementing successful ideas, the team was able to improve patient transfer time
      from the ICU to the Medical/Surgical Floor once the bed is assigned from 6 to < 2
      hr and to reduce the number of patients experiencing extreme delays (more than 12
      hr waits since the bed is assigned) from 15% to 0%. Also, as a corollary of this
      work, nursing overtime was reduced by 25% year to year between March 2008 and
      March 2009 and patient satisfaction scores were improved. A key success factor of
      the front-line team was the implementation of a sustainability plan where metric
      and process accountability is specified, together with alert flags for the
      metrics and actions to take if the alert flags are triggered.

PMID- 21199075
TI  - Development of the private practice management standards for psychology.
AB  - This paper describes the process of developing a set of private practice
      management standards to support Australian psychologists and promote high quality
      services to the public. A review of the literature was conducted to identify
      management standards relevant to psychology, which were further developed in
      consultation with a panel of experts in psychology or in the development of
      standards. Forty-three psychologists in independent private practice took part in
      either a survey (n=22) to provide feedback on the relevance of, and their
      compliance with, the identified standards, or a 6-month pilot study (n=21) in
      which a web-based self-assessment instrument evaluating the final set of
      standards and performance indicators was implemented in their practice to
      investigate self-reported change in management procedures. The pilot study
      demonstrated good outcomes for practitioners when evaluation of compliance to the
      standards was operationalized in a self-assessment format. Study results are
      based on a small sample size. Nevertheless, relevance and utility of the
      standards was found providing an initial version of management standards that
      have relevance to the practice of psychology in Australia, along with a system
      for evaluating psychological service provision to ensure best practice in service
      delivery.

PMID- 21199076
TI  - Best educational practices in pediatric emergency medicine during emergency
      medicine residency training: guiding principles and expert recommendations.
AB  - The state of pediatric emergency medicine (PEM) education within emergency
      medicine (EM) residency programs is reviewed and discussed in the context of
      shifting practice environments and new demands for a greater focus on the
      availability and quality of PEM services. The rapid growth of PEM within
      pediatrics has altered the EM practice landscape with regard to PEM. The authors
      evaluate the composition, quantity, and quality of PEM training in EM residency
      programs, with close attention paid to the challenges facing programs. A set of
      best practices is presented as a framework for discussion of future PEM training
      that would increase the yield and relevance of knowledge and experiences within
      the constraints of 3- and 4-year residencies. Innovative educational modalities
      are discussed, as well as the role of simulation and pediatric-specific patient
      safety education. Finally, barriers to PEM fellowship training among EM residency
      graduates are discussed in light of the shortage of practitioners from this
      training pathway and in recognition of the ongoing importance of the EM voice in
      PEM.

PMID- 21199077
TI  - It's time: an argument for a national emergency medicine education research
      center.
AB  - Education research in emergency medicine has made some advances, but still
      suffers from poorly designed studies and isolated projects that are small and
      cannot be generalized to other institutions. This commentary argues for the need
      of an emergency medicine education research group (EMERG). EMERG would facilitate
      and coordinate better quality educational research projects at multiple
      institutions. This in turn would promote faculty development in education
      research and potentially result in improved educational outcomes and patient
      care.

PMID- 21199078
TI  - The CORD Academy for scholarship in education in emergency medicine.
AB  - In 2010 the Council of Emergency Medicine Residency Directors (CORD) established
      an Academy for Scholarship in Education in Emergency Medicine to define, promote,
      recognize, and reward excellence in education, education research, and education
      leadership in emergency medicine. In this article we describe the mission and
      aims of the Academy. Academies for medical educators are widespread in medical
      schools today and have produced many benefits both for faculty and for
      educational programs. Little effort, however, has been devoted to such a model in
      graduate medical education specialty societies. While CORD and other emergency
      medicine organizations have developed numerous initiatives to advance excellence
      in education, we believe that this effort will be accelerated if housed in the
      form of an Academy that emphasizes scholarship in teaching and other education
      activities. The CORD Academy for Scholarship in Education in Emergency Medicine
      is a new model for promoting excellence in education in graduate medical
      education specialty societies.

PMID- 21199079
TI  - Critical appraisal of emergency medicine educational research: the best
      publications of 2009.
AB  - OBJECTIVES: The objective was to critically appraise and highlight
      methodologically superior medical education research specific to emergency
      medicine (EM) published in 2009. METHODS: A search of the English language
      literature in 2009 querying Ovid MEDLINE In-Process & Other Non-Indexed
      Citations, Ovid MEDLINE 1950 to Present, Web of Science, Education Resources
      Information Center (ERIC), and PsychInfo identified 36 EM studies that used
      hypothesis-testing or observational investigations of educational interventions.
      Six reviewers independently ranked all publications based on 10 criteria,
      including four related to methodology, that were chosen a priori to standardize
      evaluation by reviewers. This was a refinement of the methods used to appraise
      medical education published in 2008. RESULTS: Seven studies met the standards as
      determined by the averaged rankings and are highlighted and summarized here. This
      year, 16 of 36 (44%) identified studies had funding, compared to 11 of 30 (36%)
      identified last year; five of seven (71%) highlighted publications were funded in
      2009 compared to three of five (60%) highlighted in 2008. Use of technology in
      medical education was reported in 14 identified and four highlighted
      publications, with simulation being the most common technology studied. Five of
      the seven (71%) featured publications used a quasi-experimental or experimental
      design, one was observational, and one was qualitative. Practice management
      topics, including patient safety, efficiency, and revenue generation, were
      examined in seven reviewed studies. CONCLUSIONS: Thirty-six medical education
      publications published in 2009 focusing on EM were identified. This critical
      appraisal reviews and highlights seven studies that met a priori quality
      indicators. Current trends are noted.

PMID- 21199080
TI  - Emergency medicine in the medical school curriculum.
AB  - Emergency medicine (EM) is a dynamic specialty that continues to define itself as
      a fertile training ground for medical students. Throughout the years, a number of
      U.S. medical schools have incorporated topics germane to EM training (basic
      cardiac life support, principles of wound care, splinting, basic procedural
      skills training, etc.) into the medical school curriculum. By virtue of their
      broad-based training and the unique patient care environment that they practice
      in, EM specialists can serve a multitude of educational roles in the medical
      school. Whether serving as a problem-based learning facilitator, collaborating
      with basic scientists, or teaching medical history-taking and physical
      examination skills in the emergency department (ED), EM faculty can effectively
      teach future physicians in training. Although opportunities for teaching will
      vary by institution, often all it takes to get involved is asking. Teaching can
      take place in the ED, classroom, or simulation center, both in the preclinical
      and in the clinical curriculum. EM faculty may be well suited to help teach
      procedural skills to students as they enter their clinical clerkships. A formal
      rotation in EM can also assist the medical school in achieving their
      institutional objectives or in identifying ways to satisfy the Liaison Committee
      on Medical Education's objectives. Patients presenting to the ED span the entire
      spectrum: young and old, sick and not sick. It is this variety of cases that
      makes the ED a truly valuable setting for educating students.

PMID- 21199081
TI  - Anatomy of a clerkship test.
AB  - Written examinations are frequently used to assess medical student performance.
      Within emergency medicine (EM), a National Board of Medical Examiners (NBME)
      subject examination for EM clerkships does not exist. As a result, clerkship
      directors frequently generate examinations within their institution. This article
      reviews the literature behind the use of standardized examinations in evaluating
      medical student performance, describes methods for generating well-written test
      questions, reviews the statistical concepts of reliability and validity that are
      necessary to evaluate an examination, and proposes future directions for testing
      EM students.

PMID- 21199082
TI  - Inaccuracy of the global assessment score in the emergency medicine standard
      letter of recommendation.
AB  - OBJECTIVES: The standard letter of recommendation (SLOR) is used by most
      emergency medicine (EM) faculty to submit evaluations for medical students
      applying for EM residency programs. In the global assessment score (GAS) section,
      there is a crucial summative question that asks letter writers to estimate the
      applicant's rank order list (ROL) position in their own program. The primary aim
      of the study was to determine if these estimated global assessment tiers agreed
      with the actual ROL, using the criteria recommended by the Council of Emergency
      Medicine Residency Directors (CORD). METHODS: Data from SLORs written by EM
      faculty from five California institutions were retrospectively collected from the
      2008-2009 residency application year. Descriptive and comparative statistical
      analyses were performed using the documented GAS tiers and actual ROL positions.
      RESULTS: A total of 105 SLORs were reviewed from the five participating
      institutions. Three SLORs were excluded and 102 were analyzed. Only 27 (26%)
      SLORs documented a GAS tier that accurately predicted the applicant's actual ROL
      position. The GAS tier overestimated the applicant's position on the ROL in 67
      (66%) SLORs, whereas it underestimated the position in eight (8%) SLORs. Accuracy
      was poor regardless of the number of letter writers on the SLOR (p = 0.890), the
      writer's administrative title (p = 0.326), whether the student was a home or
      visiting student (p = 0.801), or if the student had prior EM rotation experience
      (p = 0.793). CONCLUSIONS: Standard letter of recommendation writers are
      inaccurate in estimating the ROL position of the applicant using the GAS tier
      criteria. The GAS tiers were accurate only 26% of the time. Because of the
      valuable role that the SLOR plays in determining an applicant's competitiveness
      in the National Resident Matching Program (NRMP) in EM, future discussion should
      focus on improving the consistency and accuracy of the GAS section. Furthermore,
      there needs to be a national dialogue to reassess the utility of the criterion
      based GAS within the SLOR.

PMID- 21199083
TI  - Curriculum design of a case-based knowledge translation shift for emergency
      medicine residents.
AB  - BACKGROUND: Principles of evidence-based medicine (EBM) may be inconsistently
      applied to clinical decision-making due to lack of practice-based training,
      experience, and time. OBJECTIVES: The authors sought to design, implement, and
      test the feasibility of an experiential learning model for senior emergency
      medicine (EM) residents to apply EBM principles during real-time clinical
      practice. METHODS: Targeted program evaluation of this learning model was
      conducted through a prospective observational cohort study involving EM residents
      at a large, urban, 4-year EM residency program. The curriculum development of a
      case-based knowledge translation shift followed Kern's six-step design process.
      Subjects asynchronously completed a 1-hour EBM tutorial and were then assigned to
      clinical shifts in which they contributed to the care of emergency department
      (ED) patients by completing formal literature searches related to active
      management questions. Pre- and post-intervention self-assessments of practice
      norms and attitudes were used to evaluate the effect of this experiential
      learning model for individual residents. Self-assessments of the likelihood that
      the experience would result in future practice change were reported on a five
      point Likert scale (1 = greatly impeded, 2 = somewhat impeded, 3 = no change, 4 =
      somewhat improved, 5 = greatly improved). Subjects presented available evidence
      to the primary ED team, formally disseminated their findings as a brief "EBM
      rounds" at sign-out and completed an "EBM consult note" and case log to document
      shift performance. Changes in patient management and/or disposition were
      recorded. EBM search questions and resultant findings were entered in a local
      database. RESULTS: Of the 45 eligible senior EM resident shifts, 91% resulted in
      complete sets of performance data and self-assessments. A total of 80 patient
      encounters were documented during 45 scheduled shifts over a 3-month study
      period. Literature review took a mean (+/-SD) of 36.2 (+/-26.4) minutes per case.
      During the 3-hour interval before or after shift sign-out, residents completed a
      mean (+/-SD) of 2.11 (+/-1.4) literature searches and recorded a mean (+/-SD) of
      3.0 (+/-1.5) articles for each case. Alterations in ED management for 13 of 80
      patient encounters (16.3%) were documented to be the direct result of on-shift
      literature searches. CONCLUSIONS: Case-based knowledge translation shifts for
      senior EM residents can provide opportunities to practice EBM skills in the ED.
      This experiential learning model may result in future practice change by resident
      learners, as well as affect the management of active patients in the ED.

PMID- 21199084
TI  - Rotating resident didactics in the emergency department: a cross-sectional survey
      on current curricular practices.
AB  - OBJECTIVES: Rotating (non-emergency medicine [EM]) residents perform clinical
      rotations in many academic emergency departments (EDs). The primary objective of
      this work was to quantify characteristics of rotating residents and the didactic
      curricula offered to them during their EM rotations. Secondary objectives were to
      identify barriers to instituting such didactics and to establish ideal curricular
      contents. METHODS: A Web-based survey was administered by e-mail to residency
      directors of all U.S. allopathic EM residency programs. Consent was obtained in
      the first part of the survey, and the study was deemed exempt from full review by
      the institutional review board. Questions solicited information regarding type
      and quantity of rotating residents in their main EDs, the "didactic educational
      format" available to rotating residents, and ideal and actual didactic curricular
      contents. Statistics were reported as proportions and means with 95% confidence
      intervals (CIs) and medians with interquartile ranges (IQRs). RESULTS: Surveys
      were sent to 143 programs, and the response rate was 71%. Ninety-nine percent of
      respondents had rotating residents in their EDs, and the median number per month
      was 4 (IQR = 3-6). Five percent of respondents had established didactic curricula
      specifically for rotating residents, and 64% sent them to either EM resident or
      medical student lectures. Thirty-one percent of programs reported no didactics,
      and 65% of these felt there was no need for such education. Resuscitation,
      trauma, and toxicology were cited as the most important subjects for actual and
      ideal curricula. CONCLUSIONS: Most academic EDs have rotating residents, but very
      few provide didactic education specific to their learning needs and almost a
      third provide no didactics.

PMID- 21199086
TI  - An evaluation of resident work profiles, attending-resident teaching
      interactions, and the effect of variations in emergency department volume on
      each.
AB  - OBJECTIVES: This study examines the effect of variations in emergency department
      (ED) volume on physician work efficiency (new patients per hour) and work profile
      (patient-related activities, including both direct and indirect patient care) and
      whether these differ between first- (Postgraduate Year [PGY]1) and third- (PGY3)
      year residents. The authors also determine if changes in volume are associated
      with changes in teaching interactions between attending and resident physicians.
      METHODS: This was a prospective observational study of resident and attending
      physicians in the ED. Research assistants (RAs) followed ED residents during
      clinical shifts and recorded a multitude of data including the amount of time
      spent in specific activities, the number of new patients seen, and the frequency
      of attending physician teaching interactions. RESULTS: Third-year residents see
      more new patients per hour (1.79 vs. 1.16, p < 0.001) than do their first-year
      counterparts. In addition, third-year residents spend almost 50% less time with
      each patient (10.7 minutes vs. 19.4 minutes, p < 0.001), and first-year residents
      spend three times as much time per shift discussing patients with attending
      physicians (59.4 minutes vs. 27.3 minutes, p = 0.002). More of the PGY1/attending
      interactions resulted in educational exchanges (54.9% vs. 34.6%, p = 0.003). PGY1
      residents also spend more time on dictations per patient (9.6 minutes vs. 5.4
      minutes, p = 0.01) and more time on paperwork per patient (18.5 minutes vs. 6.5
      minutes, p = 0.007). As ED volume tripled, PGY1 residents were able to increase
      their patient load to a greater extent than were PGY3 residents by decreasing the
      length of each patient encounter as volume increased. Overall, ED volume had no
      effect on the number of teaching interactions, although the length of exchange
      decreased as volume increased. CONCLUSIONS: Third-year residents see and carry
      more patients than do their first-year counterparts. They do so primarily by
      decreasing the amount of time spent with patients and attendings and working more
      efficiently overall. However, they are not as capable of altering their work
      profiles in the face of increased volume as their first-year counterparts. While
      the length of teaching interactions is decreased as volume increases, the number
      of those interactions resulting in teaching remains constant regardless of
      volume.

PMID- 21199085
TI  - Incorporating evidence-based medicine into resident education: a CORD survey of
      faculty and resident expectations.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME)
      invokes evidence-based medicine (EBM) principles through the practice-based
      learning core competency. The authors hypothesized that among a representative
      sample of emergency medicine (EM) residency programs, a wide variability in EBM
      resident training priorities, faculty expertise expectations, and curricula
      exists. OBJECTIVES: The primary objective was to obtain descriptive data
      regarding EBM practices and expectations from EM physician educators. Our
      secondary objective was to assess differences in EBM educational priorities among
      journal club directors compared with non-journal club directors. METHODS: A 19
      question survey was developed by a group of recognized EBM curriculum innovators
      and then disseminated to Council of Emergency Medicine Residency Directors (CORD)
      conference participants, assessing their opinions regarding essential EBM skill
      sets and EBM curricular expectations for residents and faculty at their home
      institutions. The survey instrument also identified the degree of interest
      respondents had in receiving a free monthly EBM journal club curriculum. RESULTS:
      A total of 157 individuals registered for the conference, and 98 completed the
      survey. Seventy-seven (77% of respondents) were either residency program
      directors or assistant/associate program directors. The majority of participants
      were from university-based programs and in practice at least 5 years. Respondents
      reported the ability to identify flawed research (45%), apply research findings
      to patient care (43%), and comprehend research methodology (33%) as the most
      important resident skill sets. The majority of respondents reported no formal
      journal club or EBM curricula (75%) and do not utilize structured critical
      appraisal instruments (71%) when reviewing the literature. While journal club
      directors believed that resident learners' most important EBM skill is to
      identify secondary peer-reviewed resources, non-journal club directors identified
      residents' ability to distinguish significantly flawed research as the key skill
      to develop. Interest in receiving a free monthly EBM journal club curriculum was
      widely accepted (89%). CONCLUSIONS: Attaining EBM proficiency is an expected
      outcome of graduate medical education (GME) training, although the specific
      domains of anticipated expertise differ between faculty and residents. Few
      respondents currently use a formalized curriculum to guide the development of EBM
      skill sets. There appears to be a high level of interest in obtaining EBM journal
      club educational content in a structured format. Measuring the effects of
      providing journal club curriculum content in conjunction with other EBM
      interventions may warrant further investigation.

PMID- 21199087
TI  - A core competency-based objective structured clinical examination (OSCE) can
      predict future resident performance.
AB  - OBJECTIVES: This study evaluated the ability of an objective structured clinical
      examination (OSCE) administered in the first month of residency to predict future
      resident performance in the Accreditation Council for Graduate Medical Education
      (ACGME) core competencies. METHODS: Eighteen Postgraduate Year 1 (PGY-1)
      residents completed a five-station OSCE in the first month of postgraduate
      training. Performance was graded in each of the ACGME core competencies. At the
      end of 18 months of training, faculty evaluations of resident performance in the
      emergency department (ED) were used to calculate a cumulative clinical evaluation
      score for each core competency. The correlations between OSCE scores and clinical
      evaluation scores at 18 months were assessed on an overall level and in each core
      competency. RESULTS: There was a statistically significant correlation between
      overall OSCE scores and overall clinical evaluation scores (R = 0.48, p < 0.05)
      and in the individual competencies of patient care (R = 0.49, p < 0.05), medical
      knowledge (R = 0.59, p < 0.05), and practice-based learning (R = 0.49, p < 0.05).
      No correlation was noted in the systems-based practice, interpersonal and
      communication skills, or professionalism competencies. CONCLUSIONS: An early
      residency OSCE has the ability to predict future postgraduate performance on a
      global level and in specific core competencies. Used appropriately, such
      information can be a valuable tool for program directors in monitoring residents'
      progress and providing more tailored guidance.

PMID- 21199088
TI  - Direct observation evaluations by emergency medicine faculty do not provide data
      that enhance resident assessment when compared to summative quarterly
      evaluations.
AB  - OBJECTIVES: The purpose of this study was to compare quarterly global evaluations
      with direct observation evaluations to determine if direct observation
      evaluations provide unique data compared to those obtained from quarterly global
      evaluations. METHODS: This observational, cohort study was performed at a 3-year
      emergency medicine (EM) residency program with 10 residents per year. Faculty
      used an online Web-based evaluation system to complete quarterly global
      evaluations and patient-specific direct observation evaluations. Two scores were
      collected for each resident within each quarterly evaluation period: 1) the
      quarterly evaluation score was the mean score across all faculty who performed a
      quarterly evaluation and, 2) the direct observation score was the mean score
      across all faculty who performed a direct observation evaluation. Pearson
      correlation coefficients were performed across these two groups of evaluations.
      RESULTS: Over the 4-year period of the study 296 complete data sets were
      available for the analysis. When the quarterly evaluation score was correlated
      with the direct observation score for each resident at the same evaluation
      period, we found a very high correlation for each of the eight evaluation
      questions (r = 0.95-0.96, p < 0.0001). When these evaluations were stratified
      based on the number of direct observation evaluations that were performed during
      the evaluation period of interest, the correlation between the quarterly
      evaluation and the direct observation scores increased as the number of direct
      observations in the evaluation period increased. The evaluation scores from the
      faculty who had performed both direct observation and quarterly evaluation
      methods during the same resident evaluation period were highly correlated even
      with small numbers of evaluators. CONCLUSIONS: Direct observations are highly
      correlated with quarterly evaluations when there are greater than three direct
      observation evaluations completed; however, this correlation drops significantly
      when the number of direct observations is lower. Direct observation evaluations
      provide similar data when compared with data obtained from quarterly global
      evaluations.

PMID- 21199089
TI  - Optimizing resident training: results and recommendations of the 2009 Council of
      Residency Directors consensus conference.
AB  - This paper reports the results of a consensus conference of the Council of
      Emergency Medicine Residency Directors (CORD) to discuss the experiential
      training component of residency education in the emergency department (ED) and to
      make recommendations on structuring clinical training. Self-selected emergency
      medicine (EM) educators discussed experiential training focusing on three topic
      areas: 1) methods to optimize training in the clinical setting, 2) identification
      of goals and objectives by training year, and 3) determination of measurable
      behaviors demonstrating achievement of goals and objectives by residents. Topic
      areas were organized into the following questions: 1) what is the optimal number
      and evolution of ED shifts for EM residents during their residency training, 2)
      what clinical skills are expected of a resident at each level of training, and 3)
      what objective measures should be used to provide evidence of resident
      competency? Participants attended a lecture on the goals of the conference, the
      questions to be answered, and the role and implementation of deliberate practice
      into experiential training. Attendees were divided into three groups, each
      discussing one question. Each group had two discussion leaders. All discussions
      were digitally recorded for accuracy. After discussion all groups reconvened and
      reported summaries of discussions and recommendations to ensure group agreement.
      There were 59 participants representing 42 training programs. Educators agree
      that essential features of designing the ED clinical experience include the need
      to: 1) structure and tailor the clinical experience to optimize learning, 2)
      establish expectations for clinical performance based on year of training, and 3)
      provide feedback that is explicit to year-specific performance expectations.

PMID- 21199090
TI  - Scholarly tracks in emergency medicine.
AB  - Over the past decade, some residency programs in emergency medicine (EM) have
      implemented scholarly tracks into their curricula. The goal of the scholarly
      track is to identify a niche in which each trainee focuses his or her scholarly
      work during residency. The object of this paper is to discuss the current use,
      structure, and success of resident scholarly tracks. A working group of residency
      program leaders who had implemented scholarly tracks into their residency
      programs collated their approaches, implementation, and early outcomes through a
      survey disseminated through the Council of Emergency Medicine Residency Directors
      (CORD) list-serve. At the 2009 CORD Academic Assembly, a session was held and
      attended by approximately 80 CORD members where the results were disseminated and
      discussed. The group examined the literature, discussed the successes and
      challenges faced during implementation and maintenance of the tracks, and
      developed a list of recommendations for successful incorporation of the scholarly
      track structure into a residency program. Our information comes from the
      experience at eight training programs (five 3-year and three 4-year programs),
      ranging from 8 to 14 residents per year. Two programs have been working with
      academic tracks for 8 years. Recommendations included creating clear goals and
      objectives for each track, matching track topics with faculty expertise,
      protecting time for both faculty and residents, and providing adequate mentorship
      for the residents. In summary, scholarly tracks encourage the trainee to develop
      an academic or clinical niche within EM during residency training. The benefits
      include increased overall resident satisfaction, increased success at obtaining
      faculty and fellowship positions after residency, and increased production of
      scholarly work. We believe that this model will also encourage increased numbers
      of trainees to choose careers in academic medicine.

PMID- 21199091
TI  - Guiding principles for resident remediation: recommendations of the CORD
      remediation task force.
AB  - Remediation of residents is a common problem and requires organized, goal
      directed efforts to solve. The Council of Emergency Medicine Residency Directors
      (CORD) has created a task force to identify best practices for remediation and to
      develop guidelines for resident remediation. Faculty members of CORD volunteered
      to participate in periodic meetings, organized discussions and literature reviews
      to develop overall guidelines for resident remediation and in a collaborative
      authorship of this article identifying best practices for remediation. The task
      force recommends that residency programs: 1. Make efforts to understand the
      challenges of remediation, and recognize that the goal is successful correction
      of deficits, but that some deficits are not remediable. 2. Make efforts aimed at
      early identification of residents requiring remediation. 3. Create objective,
      achievable goals for remediation and maintain strict adherence to the terms of
      those plans, including planning for resolution when setting goals for
      remediation. 4. Involve the institution's Graduate Medical Education Committee
      (GMEC) early in remediation to assist with planning, obtaining resources, and
      documentation. 5. Involve appropriate faculty and educate those faculty into the
      role and terms of the specific remediation plan. 6. Ensure appropriate
      documentation of all stages of remediation. Resident remediation is frequently
      necessary and specific steps may be taken to justify, document, facilitate, and
      objectify the remediation process. Best practices for each step are identified
      and reported by the task force.

PMID- 21199092
TI  - Emergency medicine quality improvement and patient safety curriculum.

PMID- 21199093
TI  - Local heating as a predilatation method for measurement of vasoconstrictor
      responses with laser-Doppler flowmetry.
AB  - Studying microvascular responses to iontophoresis of vasoconstricting drugs
      contributes to a better understanding of the regulatory mechanisms of cutaneous
      vessels, but measuring these responses with laser-Doppler flowmetry at basal
      blood flow conditions is technically challenging. This study aimed to investigate
      whether the measurement of cutaneous vasoconstrictor responses to noradrenaline
      (NA) and phenylephrine (PE), delivered by iontophoresis, is facilitated by
      predilatation of the microvascular bed using local heating. We used different
      drug delivery rates (100 s * 0.12 mA, 200 s * 0.06 mA, 300 s * 0.04 mA) to
      investigate whether predilatation affects the local drug dynamics by an increased
      removal of drugs from the skin. In a predilatated vascular bed, iontophoresis of
      NA and PE resulted in a significant decrease in perfusion from the thermal
      plateau (p < 0.001). The decrease was 25-33%, depending on drug delivery rate. In
      unheated skin, a significant vasoconstriction was observed (p < 0.001), with 17%
      and 14% decrease from baseline for NA and PE, respectively. These results
      indicate that predilatating the cutaneous vascular bed by local heating
      facilitates measurement of vasoconstriction with laser-Doppler flowmetry and does
      not seem to significantly affect the result by an increased removal of drugs from
      the skin.

PMID- 21199094
TI  - Critical role for oxidative stress, platelets, and coagulation in capillary blood
      flow impairment in sepsis.
AB  - Sepsis is a complex multifaceted response to a local infectious insult. One
      important facet is the circulatory system dysfunction, which includes capillary
      bed plugging. This review addresses the mechanisms of capillary plugging and
      highlights our recent discoveries on the roles of NO, ROS, and activated
      coagulation in platelet adhesion and blood flow stoppage in septic mouse
      capillaries. We show that sepsis increases platelet adhesion, fibrin deposition
      and flow stoppage in capillaries, and that NADPH oxidase-derived ROS, rather than
      NO, play a detrimental role in this adhesion/stoppage. P-selectin and activated
      coagulation are required for adhesion/stoppage. Further, platelet adhesion in
      capillaries (i) strongly predicts capillary flow stoppage, and (ii) may explain
      why severe sepsis is associated with a drop in platelet count in systemic blood.
      Significantly, we also show that a single bolus of the antioxidant ascorbate
      (injected intravenously at clinically relevant dose of 10 mg/kg) inhibits
      adhesion/stoppage. Our data suggest that eNOS-derived NO at the platelet
      endothelial interface is anti-adhesive and required for the inhibitory effect of
      ascorbate. Because of the critical role of ROS in capillary plugging, ascorbate
      bolus administration may be beneficial to septic patients whose survival depends
      on restoring microvascular perfusion.

PMID- 21199095
TI  - An investigation into the influence of various gases and concentrations of
      sclerosants on foam stability.
AB  - BACKGROUND: Foam sclerotherapy is an increasingly popular modality in varicose
      vein treatment. Our previous work showed that the half-life of room air foam
      varied according to the percentage and type of sclerosant solution. MATERIALS AND
      METHODS: A plastic connector was used to create foam made from a combination of
      0.25%, 0.50%, and 1% sodium tetradecyl sulfate (STS) and room air, carbon dioxide
      (CO(2)), oxygen (O(2)), or a mixture of CO(2) and O(2). To measure foam
      stability, the foam half-life was defined as the time it took for half the
      original volume of sclerosing solution to settle. RESULTS: Half-life varied
      according to sclerosant concentration when room air, O(2), or a mixture of CO(2)
      and O(2) was used for foam creation but not when CO(2) was used. Room air foam is
      more than 3 times as stable as CO(2) foam and 1.5 times as stable as a mixture of
      CO(2) and O(2). CONCLUSIONS: CO(2) foam half-life did not vary according to
      sclerosant solution concentration, though room air, O(2) , and CO(2)/O(2) did.
      The half-life of room air foam is more than 3 times as long as that of CO(2) and
      1.5 times as long as that of a mixture of CO(2) and O(2). Foam half-life for room
      air and O(2) are similar at low concentrations of STS but differ at higher
      concentrations.

PMID- 21199096
TI  - Fractional photothermolysis laser treatment of male pattern hair loss.
AB  - BACKGROUND: Various trials have been conducted on the management of male pattern
      hair loss (MPHL). A variety of laser and light sources have been used for the
      treatment of MPHL. OBJECTIVE: To understand the effects of a 1,550-nm fractional
      erbium-glass laser on the hair cycle in an alopecia mouse model and to study the
      clinical effects of the same laser used as treatment for MPHL. MATERIALS AND
      METHODS: Irradiation was applied to the shaved skin of C3H/HeN mice using various
      energy and density settings and varied irradiation intervals. In a clinical pilot
      study involving human subjects, 20 participants were treated over five sessions
      at 2-week intervals. A fractional photothermolysis laser was used at the energy
      of 5 mJ and a total density of 300 spots/cm(2). RESULTS: In the animal study, the
      hair stimulation effects were dependent upon the energy level, density, and
      irradiation interval. The anagen conversion of hair and the increase in Wnt 5a,
      beta-catenin signals were observed. In the human pilot study, incremental
      improvements in hair density and growth rate were observed. CONCLUSIONS: This
      pilot study showed that a 1,550-nm fractional erbium-glass laser might induce
      hair growth, but more intensive studies are required to clarify the clinical
      applications of this treatment.

PMID- 21199097
TI  - Optimizing closure materials for upper lid blepharoplasty: a randomized,
      controlled trial.
AB  - BACKGROUND: Although upper eyelid blepharoplasty is a common procedure,
      subtleties in surgical technique can affect cosmetic outcomes. Suture materials
      commonly used include polypropylene, monofilament nylon, fast-absorbing gut, and
      ethylcyanoacrylate (ECA) tissue adhesive. OBJECTIVE: To assess upper lid
      blepharoplasty scars in participants whose incision had been closed with 6-0
      polypropylene sutures, 6-0 fast-absorbing gut sutures, or ECA. MATERIALS AND
      METHODS: A randomized, split-eyelid, single-blind, prospective study of the short
      (1 month) and intermediate-term (3 months) efficacy of polypropylene, fast
      absorbing gut, and ECA on 36 consecutive upper lid blepharoplasties. Participants
      and a blinded physician evaluator evaluated cosmetic outcome 1 and 3 months after
      the procedure. RESULTS: Three subgroups tested were ECA versus fast-absorbing
      gut, ECA versus polypropylene, and fast-absorbing gut versus polypropylene. At 1
      month, ECA was superior to fast-absorbing gut (p=.03) and had a marginally better
      outcome than polypropylene (p=.25), and polypropylene had an equivalent outcome
      to fast-absorbing gut (p=.46). At 3-month follow-up, ECA remained superior to
      fast-absorbing gut (p=.03). CONCLUSION: Although sutured epidermal closure and
      tissue adhesive are highly efficacious for upper eyelid blepharoplasty,
      physicians and participants felt that cosmesis with ECA was superior to that with
      fast-absorbing gut.

PMID- 21199100
TI  - European Federation of Neurological Societies/Peripheral Nerve Society guideline
      on management of multifocal motor neuropathy. Report of a joint task force of the
      European Federation of Neurological Societies and the Peripheral Nerve Society-
      first revision.
AB  - A European Federation of Neurological Societies/Peripheral Nerve Society
      consensus guideline on the definition, investigation, and treatment of multifocal
      motor neuropathy (MMN) was published in 2006. The aim is to revise this
      guideline. Disease experts considered references retrieved from MEDLINE and
      Cochrane Systematic Reviews published between August 2004 and July 2009 and
      prepared statements that were agreed to in an iterative fashion. The Task Force
      agreed on Good Practice Points to define clinical and electrophysiological
      diagnostic criteria for MMN, investigations to be considered, and principal
      recommendations for treatment.

PMID- 21199101
TI  - Update on neuropathies associated with monoclonal gammopathy of undetermined
      significance (2008-2010).
AB  - Studies on paraproteinemic neuropathies have appeared in the last 2 years
      improving the diagnosis of these neuropathies, clarifying their pathogenesis, and
      informing practice by randomized clinical trial publications. Two recent
      randomized controlled trials with rituximab failed to provide evidence of
      efficacy in primary outcome measures, despite the fact that anti-myelin
      associated glycoprotein (MAG) antibodies were reduced in most treated patients.
      This discrepancy, besides inducing the search for more effective therapy for this
      neuropathy, indicates that some aspects on the pathogenesis of this neuropathy
      probably need further clarification.

PMID- 21199102
TI  - Respiratory muscle weakness in peripheral neuropathies.
AB  - Common peripheral neuropathies do not usually cause diaphragmatic weakness and
      subsequent respiratory compromise. However, respiratory involvement is relatively
      common in Guillain-Barre syndrome (GBS). Experience in GBS has led to a
      standardized approach to manage respiratory problems in peripheral neuropathies.
      Diaphragmatic weakness is not common in chronic inflammatory demyelinating
      polyneuropathy and extremely rare in multifocal motor neuropathy. The linkage has
      been described between certain subtypes of Charcot-Marie-Tooth (CMT) disease such
      as CMT2C and CMT4B1 and diaphragmatic weakness. A correlation usually has not
      been found between electrophysiologic findings and clinical respiratory signs or
      spirometric abnormalities in peripheral neuropathies except in amplitudes of
      evoked phrenic nerve responses. Careful and frequent assessment of respiratory
      function by a qualified team of healthcare professionals and physicians is
      essential. Criteria established for mechanical ventilation in GBS cases may be
      applied to other peripheral neuropathies with respiratory compromise as
      necessary.

PMID- 21199103
TI  - Measures of chemotherapy-induced peripheral neuropathy: a systematic review of
      psychometric properties.
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) remains the principal dose
      limiting toxicity of many agents. This systematic review evaluates available CIPN
      measures and provides rationale for selection of measures in this field. Searches
      of Medline (1966-2010), CINAHL (1966-2010), Embase (1966-2010), and Cochrane
      (1988-2010) databases were performed. To be selected, studies had to include (1)
      subjects receiving peripheral neurotoxic chemotherapy for cancer and (2) a
      primary purpose of psychometric evaluation of CIPN measures. A modified Quality
      of Diagnostic Accuracy Studies (QUADAS) tool coded psychometric study quality,
      with 0-7 score overall possible (higher score indicating better quality). A total
      of 15 studies qualified for evaluation. Overall studies were of moderate quality,
      with 10 of 15 receiving a 4-5 QUADAS score. Averaged quality scores for two
      repeatedly studied measures, Total Neuropathy Score (TNS) versions and Functional
      Assessment of Cancer-Gynecologic Oncology Group, neurotoxicity (FACT/GOG-Ntx),
      were 5.4 and 4.5, respectively. Two measures emerged as potentially useful for
      clinical trials and patient care. The FACT/GOG-Ntx is a subjective measure of
      CIPN-related quality of life (QoL). TNS clinical versions incorporate both
      subjective measures and objective examinations of nerve function. However, to
      improve QUADAS scoring, additional research is needed focusing on other
      psychometric aspects such as responsiveness of CIPN outcome measures.

PMID- 21199104
TI  - Chronic inflammatory demyelinating polyneuropathy disease activity status:
      recommendations for clinical research standards and use in clinical practice.
AB  - Defining long-term outcomes in chronic inflammatory demyelinating polyneuropathy
      (CIDP) has been complicated by varying definitions of treatment response and
      differing scales measuring impairment or disability. An expert panel was convened
      to devise a CIDP Disease Activity Status (CDAS) and to classify long-term outcome
      by applying it to 106 patients with a consensus diagnosis of CIDP. Sixty of these
      cases were graded blindly by three independent reviewers to assess inter-rater
      reliability. The mean duration of follow-up was 6.4 years (range, 3 months-23
      years). Eleven percent of patients were classified as cured (stable examination
      and off treatment for >=5 years), 20% were in remission (stable and off treatment
      for <5 years), 44% had stable active disease but required ongoing therapy for at
      least 1 year, 7% were improving after recent initiation of therapy, and 18% had
      unstable active disease (treatment naive or treatment refractory). Excellent
      inter-rater reliability was observed (kappa scores: 0.93-0.97; p < 0.0001). The
      CDAS is considered a simple and reproducible tool to classify patients with CIDP
      according to disease activity and treatment status that can be applied easily in
      practice and potentially to select patients for clinical trials.

PMID- 21199105
TI  - Phenotypical features of the p.R120W mutation in the GDAP1 gene causing autosomal
      dominant Charcot-Marie-Tooth disease.
AB  - Mutations in the ganglioside-induced-differentiation-associated protein 1 gene
      (GDAP1) can cause Charcot-Marie-Tooth (CMT) disease with demyelinating (CMT4A) or
      axonal forms (CMT2K and ARCMT2K). Most of these mutations present a recessive
      inheritance, but few autosomal dominant GDAP1 mutations have also been reported.
      We performed a GDAP1 gene screening in a clinically well-characterized series of
      81 index cases with axonal CMT neuropathy, identifying 17 patients belonging to 4
      unrelated families in whom the heterozygous p.R120W was found to be the only
      disease-causing mutation. The main objective was to fully characterize the
      neuropathy caused by this mutation. The clinical picture included a mild-moderate
      phenotype with onset around adolescence, but great variability. Consistently,
      ankle dorsiflexion and plantar flexion were impaired to a similar degree. Nerve
      conduction studies revealed an axonal neuropathy. Muscle magnetic resonance
      imaging studies demonstrated selective involvement of intrinsic foot muscles in
      all patients and a uniform pattern of fatty infiltration in the calf, with distal
      and superficial posterior predominance. Pathological abnormalities included
      depletion of myelinated fibers, regenerative clusters and features of axonal
      degeneration with mitochondrial aggregates. Our findings highlight the relevance
      of dominantly transmitted p.R120W GDAP1 gene mutations which can cause an axonal
      CMT with a wide clinical profile.

PMID- 21199106
TI  - Distribution of Th17 cells and Th1 cells in peripheral blood and cerebrospinal
      fluid in chronic inflammatory demyelinating polyradiculoneuropathy.
AB  - Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune
      mediated demyelinating disease of the peripheral nervous system. Th17 and Th1
      cells contribute to the pathogenesis of most autoimmune diseases, but little is
      known about their distribution and reciprocal relationship in CIDP. In this
      study, we analyzed the distribution of Th17, Th1, and Th17/Th1 cells in the
      peripheral blood and cerebrospinal fluid (CSF). The results showed that the
      frequency of Th17 cells was significantly higher in the peripheral blood
      mononuclear cell (PBMCs) and CSF of active CIDP in comparison with remitting CIDP
      or to other non-inflammatory neurological diseases (ONDs), accompanied by similar
      findings for Th17/Th1 cells. Both active and remitting CIDP have higher
      percentage of Th1 cells in the CSF than OND. CSF protein levels positively
      correlated with the frequencies of Th17 cells either in the PBMCs or CSF of
      active CIDP, while there was no significant correlation with Th1 cells. In line
      with these observations, the levels of interleukin-17 (IL-17) in plasma and
      transcript factors retinoic acid receptor-related orphan receptor (ROR)gammat
      expressed by PBMCs were significantly higher in the active CIDP than remitting
      CIDP or OND. In summary, our preliminary findings suggest that elevated numbers
      of inflammatory T cells, especially for Th17 cells, might be an important
      determinant in the evolution of CIDP.

PMID- 21199107
TI  - On the longevity of resident endoneurial macrophages in the peripheral nervous
      system: a study of physiological macrophage turnover in bone marrow chimeric
      mice.
AB  - Macrophages are intimately involved in the pathogenesis of peripheral nervous
      system (PNS) disorders. Recently, we characterized a resident endoneurial
      macrophage population, which contributes rapidly to the endoneurial macrophage
      response in PNS diseases. Unlike microglial cells, resident macrophages undergo a
      physiological turnover of 50% in the sciatic nerve and 80% in dorsal root ganglia
      (DRG) within 12 weeks. Further information about the dynamics of this turnover is
      not available. This study examined the macrophage turnover in the sciatic nerve
      and DRGs over a longer period and addresses the question whether the turnover of
      resident macrophages is complete or whether there is a truly resident endoneurial
      macrophage population. We used chimeric mice carrying GFP(+) bone marrow and
      immunohistochemistry to detect hematogenous (GFP(+)) endoneurial macrophages
      after turnover. Non-exchanged, resident macrophages were GFP(-). Quantification
      of GFP(+) and GFP(-) macrophages revealed a maximal turnover of 75%, reached in
      DRGs after 12 weeks and in sciatic nerves after 36 weeks. GFP(-) long-term
      resident macrophages were further characterized after sciatic nerve injury, where
      they participated in the early macrophage response of Wallerian degeneration. Our
      results point toward a small but truly resident PNS macrophage population. These
      macrophages are an interesting target for further characterization and might have
      a distinct role in peripheral nerve disease.

PMID- 21199108
TI  - Bortezomib-induced inflammatory neuropathy.

PMID- 21199109
TI  - Distal nerve excitability and conduction studies in a case of rapidly regressive
      acute motor neuropathy with multiple motor conduction blocks.

PMID- 21199110
TI  - ISPOR 13th Annual European Congress. Abstracts.

PMID- 21199113
TI  - Abstracts presented at the 12th World Congress of the International Society for
      Diseases of the Esophagus, Kagoshima, Japan, September 2-5, 2010.

PMID- 21199114
TI  - Epidemiology and morbidity of regional anesthesia in children: a follow-up one
      year prospective survey of the French-Language Society of Paediatric
      Anaesthesiologists (ADARPEF).
AB  - BACKGROUND: The French-Language Society of Paediatric Anaesthesiologists
      (ADARPEF) designed a 1-year prospective, multicenter and anonymous study to
      update both epidemiology and morbidity of regional anesthesia in children.
      METHODS: From November 2005 to October 2006, data from participating hospitals
      were recorded using an identification form, a data recording form, and a
      complication form. Information collected included the characteristics of the
      hospitals, the number and type of regional anesthetics (RA), the age of the
      involved children as well as the incidence, and type of complications. RESULTS:
      Data collected in 47 institutions included 104,612 pure general anesthesias
      (GAs), 29,870 GAs associated with regional blocks, and 1262 pure regional blocks.
      Central blocks accounted for 34% of all RA. Peripheral blocks (66%) were upper or
      lower limb blocks (29% of peripheral blocks), trunk blocks, and face blocks
      (71%). In children aged <=3 years, the percentage of central blocks was similar
      to the peripheral ones (45% vs 55), while in older children, peripheral blocks
      were more than four times used than central ones. Complications (41 involving 40
      patients) were rare and usually minor. They did not result in any sequelae. The
      study revealed an overall rate of complication of 0.12%; CI 95% [0.09-0.17],
      significantly six times higher for central than for peripheral blocks.
      CONCLUSIONS: As a result of the low rate of complications, RA techniques have a
      good safety profile and can be used to provide postoperative analgesia. In
      addition, the results should encourage anesthesiologists to continue to use
      peripheral instead of central (including caudal) blocks as often as possible when
      appropriate.

PMID- 21199115
TI  - Use of epidural and peripheral nerve blocks at the end of life in children and
      young adults with cancer: the collaboration between a pain service and a
      palliative care service.
AB  - BACKGROUND: Clinicians may avoid continuous pain blocks in pediatric cancer
      patients at the end of life for fear of complications or of interfering with the
      desired location of death. OBJECTIVES: To examine the impact of epidural or
      peripheral nerve catheters on pain control in children and young adults with
      cancer within the last 3 months of life. METHODS: We retrospectively reviewed the
      medical records to assess pain scores, systemic opioid requirements, and impact
      on death at the preferred location. RESULTS: Ten patients (4.4-21.3 years of
      age), nine with solid tumors, one with lymphoma, had 14 devices (11 epidural, 3
      peripheral nerve catheters) for a range of 3-81 days. Twelve of 13 catheters
      provided improvement by at least one of three criteria: improved mean pain scores
      at 24 h (8 of 13) and decreased opioid requirement at 24 h in nine cases and at
      day 5 in nine cases. Eight patients died in their preferred setting. Six patients
      had catheters (five epidural, one peripheral) until death, including two who died
      at home. In some cases, typical contraindications for indwelling catheters
      (spinal metastasis, vertebral fracture, thrombocytopenia, fever) were superseded
      by palliative care needs. We found no bleeding, infectious, or neurological
      complications. CONCLUSIONS: Our findings suggest that continuous catheter
      delivered pain blockade at the end of life contributes to analgesia, moderates
      opioid requirements, and usually does not preclude death at the preferred
      location.

PMID- 21199116
TI  - Perioperative opioid requirements are decreased in hypoxic children living at
      altitude.
AB  - OBJECTIVES: To investigate the effect of altitude on perioperative opioid
      requirements in otherwise healthy children. AIM: To investigate whether children
      living and having surgery at high altitude received different doses of fentanyl
      than those living and having surgery at sea level. BACKGROUND: Recent studies in
      animals (Anesthesiology, 105, 2006 and 715) and children with obstructive sleep
      apnea (Anesthesiology, 105, 2006 and 665; Anesthesiology 100, 2004 and 806)
      suggest that analgesic effects of exogenous opioids are enhanced by hypoxia.
      However, the effects of hypoxia on perioperative narcotic requirements in
      otherwise healthy children have not been previously reported. METHODS/MATERIALS:
      We reviewed retrospectively the opioid requirements of pediatric patients who
      underwent cleft lip or palate surgery during Smile Network International mission
      trips to Cusco and Lima, Peru between 2007 and 2009. Patients who had surgery at
      high altitude were compared to those who had surgery at sea level. All patients
      received a standardized anesthetic with intravenous fentanyl as the only
      perioperative opioid. RESULTS: Hundred and two patients had surgery at 3399 m
      above sea level (masl) (Cusco) and 169 patients had surgery at 150 masl (Lima).
      Patients at high altitude had significantly lower baseline oxygen saturations (92
      +/- 4% vs 98 +/- 3%; P < 0.001) and received 40% less opioid (1.2 +/- 0.8 vs 2.0
      +/- 1.4 MUg.kg(-1) per h; P < 0.001) compared to patients at sea level.
      CONCLUSIONS: Opioid administration was reduced in otherwise healthy children with
      altitude-induced chronic hypoxia when compared to non-hypoxic children undergoing
      similar operations under similar anesthetic regimens. Whether this difference is
      due to altitude or altitude-induced hypoxia, requires further study.

PMID- 21199117
TI  - Airway management in pediatric patients undergoing suspension laryngoscopic
      surgery for severe laryngeal obstruction caused by papillomatosis.
AB  - OBJECTIVES: To review perioperative airway management and ventilation strategy
      during the surgical removal of papilloma under suspension laryngoscopy in
      pediatric patients with severe airway obstruction. METHODS: Seventy pediatric
      patients with degree III and IV laryngeal obstruction who underwent suspension
      laryngoscopy to remove laryngeal papillomatosis, between July 2005 and March
      2009, were included in the study. All patients were intubated initially to secure
      the airway. Controlled ventilation through an endotracheal (ET) tube was used
      during the papilloma debulking near the glottis vera. Spontaneous ventilation or
      apneic technique was adopted based on the stage of the surgical procedure and the
      location of the remaining tumor. Hemodynamic parameters, pulse oxygen saturation
      (SpO(2)), and CO(2) were closely monitored, and adverse events were recorded.
      RESULTS: The duration of the surgical operation and the duration of the
      extubation period were 5-35 min and 5-20 min, respectively. Thirty cases with
      degree III and twenty cases with degree IV laryngeal obstruction received
      inhalation induction. Sixteen cases with degree III laryngeal obstruction were
      given an intravenous induction. Four patients admitted with a comatose status
      were emergently intubated without any anesthetics. The ET tube size was
      determined by assessing the opening through the tumor mass or glottic aperture
      under direct laryngoscopy. SpO(2) was maintained above 97% after the airway was
      secured and sufficient ventilation established. Controlled ventilation was used
      in all children during the bulk removal of tumor. Spontaneous respiration and
      apneic technique were adopted for the removal of the remaining tumor in the
      hypolarynx or trachea in 16 and 28 cases, respectively. Three patients had to be
      re-intubated postoperatively because of persistent desaturation or laryngospasm.
      CONCLUSION: Key points of perioperative airway management in pediatric patients
      with papillomatosis-induced severe laryngeal obstruction include careful
      preoperative airway evaluation; the proper choice of induction methods, and ET
      tube size; maintenance of an adequate depth of anesthesia; and flexible
      ventilation strategy, continuous and close monitoring during the extubation and
      postextubation period; and prompt management of adverse events.

PMID- 21199118
TI  - Comparison of Bullard laryngoscope and short-handled Macintosh laryngoscope for
      orotracheal intubation in pediatric patients with simulated restriction of
      cervical spine movements.
AB  - AIM: To compare time to intubation, time to optimal laryngoscopy, best laryngeal
      view, and success rate of intubation with pediatric Bullard laryngoscope and
      short-handled Macintosh laryngoscope in children being intubated with neck
      stabilization. BACKGROUND: Securing airway of a patient with restricted cervical
      spine movement has been a challenge faced by anaesthesiologists around the world.
      Macintosh laryngoscope with manual inline stabilization is most commonly used.
      Bullard laryngoscope is also useful in this situation as minimal neck movement
      occurs with its use. METHODS: Forty patients, ASA I or II, aged 2-10 years, were
      enrolled in this prospective, controlled, and randomized study. Patients were
      randomly allocated to one of two groups: Group MB (first laryngoscopy using short
      handled Macintosh laryngoscope followed by pediatric Bullard laryngoscope) and
      Group BM (first laryngoscopy using pediatric Bullard laryngoscope followed by
      short-handled Macintosh laryngoscope) with manual inline stabilization after
      induction of anesthesia and paralysis. Trachea was intubated orally using the
      second equipment. RESULTS: Laryngeal view when obtained was always Grade 1 with
      Bullard laryngoscope (38/38) when compared to Macintosh laryngoscope [Grade 1
      (10/40)]. The mean time to laryngoscopy (and intubation) was shorter with
      Macintosh laryngoscope [15.53 s (38.15 s)] than Bullard laryngoscope [35.21 s
      (75.71 s)], respectively. Success rate of intubation was higher with Macintosh
      laryngoscope (100%) when compared to Bullard laryngoscope (70%). CONCLUSIONS:
      Laryngoscopy and intubation is faster using a short-handled Macintosh
      laryngoscope with a higher success rate compared to pediatric Bullard
      laryngoscope in pediatric patients when manual inline stabilization is applied.

PMID- 21199119
TI  - Efficacy of different concentrations of sevoflurane administered through a face
      mask for magnetic resonance imaging in children.
AB  - BACKGROUND: The main aim of this study was to use a non-invasive method such as a
      face mask to maintain anesthesia in children during magnetic resonance imaging
      (MRI). The secondary aim was to ascertain hemodynamic-respiration parameters,
      recovery time and complications of anesthesia with the administration of
      different concentrations of sevoflurane. METHODS: This prospective and randomized
      study included 96 ASA I-II children, aged 1-10, scheduled to undergo MRI with
      anesthesia with sevoflurane through a face mask. All patients were administered
      midazolam 0.5 mg.kg(-1) orally 30 min before anesthesia induction. Sevoflurane 8%
      was given to induce anesthesia under assisted-controlled ventilation for 2 min,
      and an intravenous route was opened on the hand. Three different concentrations
      of sevoflurane were administered through a face mask under spontaneous
      respiration to maintain anesthesia. A mixture of sevoflurane, oxygen, and air of
      5 l.min(-1) was given through a face mask for anesthesia. Group 1 (n = 32)
      received 1.5% sevoflurane, Group 2 (n = 32) 1.25% sevoflurane, and Group 3 (n =
      32) 1.0% sevoflurane. Recovery time, removal from the MRI room, postanesthesia
      care unit discharge data, and complications were also recorded. Heart rate, mean
      arterial pressure (MAP), peripheral oxygen saturation (SpO(2)), respiration rate,
      and anesthesia adequacy were recorded every 5 min from the time of induction
      until completion of the MRI. RESULTS: All three groups were similar in
      demographic and hemodynamic respiratory features. MRI was successfully performed
      in 96.6% of all patients without additional intervention. Sevoflurane
      concentrations were increased for a short time in one patient in Group 1 and in
      two patients in Group 3. Oxygen flow was increased in one patient in Group 1 and
      in one patient in Group 2 as SpO(2) was lower than 95%. The mean time to eye
      opening (from discontinuation of sevoflurane to eye opening) was 155.8 +/- 50.0 s
      in Group 1, 89.5 +/- 16.0 s in Group 2, and 53.5 +/- 10.0 s in Group 3;
      differences between the groups were statistically significant (P = 0.001).
      Airways were not used on any of the patients, and none vomited or required
      endotracheal intubation or laryngeal mask anesthesia. CONCLUSIONS: We believe
      that the administration of sevoflurane at a concentration of 1% via a face mask
      under spontaneous respiration may provide light anesthesia without complications
      to induce an unarousable sleep for children during MRI.

PMID- 21199120
TI  - Pressure vs. volume control ventilation: effects on gastric insufflation with
      size-1 LMA.
AB  - BACKGROUND: In this randomized prospective study, peak airway pressure (PAP) and
      gastric insufflation were compared between volume control ventilation (VCV) and
      pressure control ventilation (PCV) using size-1 laryngeal mask airway (LMA) in
      babies weighing 2.5-5 kg. METHODS: Forty ASA I and II children, weighing 2.5-5
      kg, undergoing elective infraumbilical surgeries (duration < 60 min) were
      randomized to two groups of 20 each to receive either PCV or VCV. Patients at
      risk of aspiration, difficult airway and upper respiratory tract infection, and
      poor lung compliance were excluded. Anesthesia technique included
      sevoflurane/O(2)/N(2)O without neuromuscular blockade. PAP in PCV and tidal
      volume in VCV modes were changed to achieve adequate ventilation (P(E)CO(2) of 5
      5.4 kPa). PAP was maintained below 20 cm H(2)O. Chi-squared test, Mann-Whitney U
      test and Wilcoxon W-test were applied; P < 0.05 was considered significant.
      RESULTS: Mean PAP (cm H(2)O) was 12.2 +/- 1.09 in PCV and 13.60 +/- 0.94 in VCV
      groups (P = 0.000). The confidence interval of mean difference of PAP varied from
      0.79 to 2.10. Significant increases in abdominal circumference were observed in
      both groups: PCV: 0.94 +/- 1.04 cm and VCV: 2.2 +/- 1.3 cm; (P = 0.000). The
      SpO(2) and hemodynamic variables did not differ between the groups. One patient
      in VCV group (with PAP = 14 cm H(2)O) could not be ventilated to the target
      P(E)CO(2), and the LMA had to be replaced with tracheal tube. CONCLUSION: In
      conclusion, PCV should be the preferred mode to provide positive pressure
      ventilatio (PPV), when using the size-1 cLMA in babies weighing 2.5-5 kg, in view
      of less gastric insufflation associated with it for surgeries of brief duration.
      More studies are required to validate the clinical significance of these two
      modes of ventilation in longer procedures, in this subpopulation.

PMID- 21199121
TI  - Whole-lung lavage in infants and children with pulmonary alveolar proteinosis.
AB  - BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare alveolar filling
      syndrome where the mainstay of treatment is therapeutic whole-lung lavage (WLL).
      WLL techniques used in adults have to be modified for children because of their
      small-diameter airways. AIM: To describe a technique for WLL adapted for small
      children. METHODS: We describe a WLL technique that combines safe single-lung
      ventilation with the use of an age-appropriate endotracheal tube and selective
      occlusion of the other main bronchus with a balloon catheter through which the
      lavage is performed. Effectiveness measured by change in oxygen requirements and
      adverse effects was noted. RESULTS: We performed 64 WLL procedures in four
      children (age 13 months to 7 years; body weight 4.7-14 kg). Two children had
      idiopathic and two had secondary PAP. At referral, all children had dyspnoea at
      rest and required continuous oxygen supplementation. Two patients showed
      significantly decreased oxygen demands and radiological improvement after WLL.
      Two patients showed no significant response. The only adverse effect observed was
      transient hypoxemia. Complications comprised fluid leak at the balloon (4),
      balloon rupture (1), and pneumothorax (1). CONCLUSIONS: This technique for WLL
      combining single-lung ventilation with an endotracheal tube and lung exclusion
      for lavage with a balloon catheter can be safely and effectively performed in
      small children with PAP.

PMID- 21199122
TI  - Anesthesia for ritual circumcision in neonates.
AB  - OBJECTIVES: To ascertain whether there is medical and religious agreement that
      neonates being circumcised should have anesthesia. AIM: To enquire of pediatric
      and anesthetic surgical bodies and religious authorities, the need for and any
      objections to anesthesia. BACKGROUND: Many neonatal circumcisions are still
      carried out without anesthesia worldwide. Muslims are recommended to be
      circumcised but it is not a religious requirement. It can be carried out at any
      time, by a surgeon and anesthetist. Jewish law requires circumcision (Bris) on
      the eighth day, by a Jewish circumciser (a mohel) and is usually, but not
      essentially, in the home. RESULT: All the medical authorities agree that
      anesthesia should be administered. Religious authorities cannot find any reasons
      to avoid anesthesia. The 'any day' request for anesthesia is difficult to meet
      with a shortage of pediatric anesthetists. Local anesthesia is suitable, but
      requires skills. CONCLUSION: (i) That anesthesia should be provided for neonatal
      circumcision. (ii) That there will be difficulties in providing a professional
      service. (iii) That EMLA cream is the most practical, even if only partly
      effective. (iv) A website demonstrating application to parents would encourage
      usage.

PMID- 21199124
TI  - Reply to 'Successful resuscitation of bupivacaine-induced cardiotoxicity in a
      neonate'.

PMID- 21199125
TI  - "Pratap JN, Wilmhurst S: Anesthetic management of children with in situ Berlin
      Heart EXCOR: Pediatric Anesthesia: 2010: 20: 812-820".

PMID- 21199126
TI  - Thomsen-Friedenreich cryptantigen as a possible cause of acute intra-operative
      bronchospasm.

PMID- 21199127
TI  - Response to Anesthetic management of a rare case of Shprintzen-Goldberg
      craniosynostosis syndrome.

PMID- 21199129
TI  - Probability of survival based on etiology of cardiopulmonary arrest in pediatric
      patients.
AB  - OBJECTIVE: To aggregate data across institutions to identify, characterize, and
      differentiate potential survivors from nonsurvivors based on etiology of event.
      AIM: To evaluate the association of the cardiopulmonary resuscitation (CPR)
      duration and probability of survival (Ps), stratified by etiology of arrest.
      BACKGROUND: In-hospital cardiac arrests occur in 2-6% of pediatric patients with
      poor survival rates resulting in significant expenditures of time and resources.
      METHODS: Retrospective data from six pediatric hospitals on patients suffering
      from pulseless cardiac arrests receiving CPR for over one minute were analyzed.
      Data included demographics, reason for code, precardiac arrest diagnosis, devices
      and treatment, management strategies during cardiac arrest, compression duration,
      outcome at hospital discharge, and neurologic outcome of survivors at hospital
      discharge. Results of logistic regression analysis generated predicated
      probabilities of survival for duration of compression. Patients were stratified
      by cardiac-induced cardiac arrests (CICA) and respiratory-induced cardiac arrest
      (RICA). RESULTS: A total of 257 patients were included, and 27% of CICA and 35%
      of RICA patients survived to hospital discharge. Ps was initially lower for the
      CICA patients (Ps at 1 min = 29%) and remained constant (Ps at 60 min = 25%).
      RICA patients'Ps was higher initially (Ps at 1 min = 62%) but demonstrated a
      dramatic drop within the first 60 min of CPR (Ps at 60 min = 0.2%). CONCLUSIONS:
      Probability of survival curves based on duration of CPR was statistically
      significantly different for CICA patients compared to RICA patients.

PMID- 21199131
TI  - Who needs an IV? Retrospective service analysis in a tertiary pediatric hospital.
AB  - AIMS: The question if it is possible and safe to anesthetize children for short
      procedures without intravenous (IV) access provokes strong opinions among
      pediatric anesthetists. However, only limited data are available to support
      either side of the arguments. This pediatric university hospital provides
      anesthesia to a community dental service, led by staff anesthesiologists. A rapid
      turnover system based on inhalational induction and maintenance of anesthesia
      without mandatory IV access has been employed since 2005. METHODS: A
      retrospective service analysis was performed to identify the incidence of adverse
      anesthesia events. RESULTS: A total of 6440 children with an average (+/- SD) age
      of 8.1 (+/- 4.1) years and weight of 29.6 (+/- 13.5) kg were cared for over the 5
      year period. The total number of children refusing to undergo inhalational
      induction was 81 (1.26%) and 19 (0.3%) elected for an IV induction. One-third
      received cannulation for delivery of IV analgesia. There were no adverse
      anesthesia events requiring emergency cannulation and/or intubation over the 5
      year period. CONCLUSIONS: This service review indicates that general anesthesia
      for outpatient dental anesthesia may be safely performed without mandatory IV
      access. The technique employed in this center emphasizes the need for the
      clinician to primarily concentrate on pediatric airway management in a safe
      environment with experienced assistance. It supports the hypothesis that
      instrumentation of the airway (insertion of laryngeal mask airway) can be
      satisfactorily achieved without prior IV access.

PMID- 21199130
TI  - Ketorolac tromethamine: stereo-specific pharmacokinetics and single-dose use in
      postoperative infants aged 2-6 months.
AB  - OBJECTIVE: We determined the postoperative pharmacokinetics (PK), safety, and
      analgesic effects of ketorolac in 14 infants (aged <6 months) receiving a single
      intravenous (IV) administration of racemic ketorolac or placebo. BACKGROUND:
      Information on the PK of ketorolac in infants is limited. Unblinded studies
      suggest ketorolac may be useful in infants. METHODS: This double-blinded, placebo
      controlled study enrolled 14 infants (aged <6 months) postoperatively. At 6-18 h
      after surgery, infants were randomized to receive placebo, 0.5 mg.kg(-1), or 1
      mg.kg(-1) ketorolac IV. All infants received morphine sulfate as needed for pain
      control. Blood was collected up to 12-h postdosing. Analysis used
      noncompartmental and compartmental population modeling methods. RESULTS: In
      addition to noncompartmental and empirical Bayes PK modeling, data were
      integrated with a previously studied data set comprising 25 infants and toddlers
      (aged 6-18 months). A two-compartmental model described the comprehensive data
      set. The population estimates of the R (+) isomer were (%CV): central volume of
      distribution 1130 (10%) ml, peripheral volume of distribution 626 (25%) ml, and
      clearance from the central compartment 7.40 (8%) ml.min(-1). Those of the S (-)
      isomer were 1930 (15%) ml, 319 (58%) ml, and 39.5 (13%) ml.min(-1). Typical
      elimination half-lives were 191 and 33 min, respectively. There was a trend for
      increased clearance and central volume with increasing age and weight. The base
      model suggested that clearance of the S (-) isomer was weakly related to age;
      however, when body size adjustment was added to the model, no covariates were
      significant. Safety assessment showed no changes in renal or hepatic function
      tests, surgical drain output, or continuous oximetry between groups. Cumulative
      morphine administration showed large inter-patient variability and was not
      different between groups. CONCLUSION: Stereo-isomer-specific clearance of
      ketorolac in infants (aged 2-6 months) shows rapid elimination of the analgesic S
      (-) isomer as reported in infants aged 6-18 months. No adverse effects were seen
      after a single IV ketorolac dose.

PMID- 21199132
TI  - Pediatric cardiac anesthesia in the developing world.
AB  - More children die of congenital heart disease (CHD) in low-income countries and
      acquired cardiac disease is more frequent. Advances in diagnosis, surgery,
      perfusion and anesthesia in the developed world have had dramatic results on
      children's lives, and many forms of CHD can now be safely corrected or palliated.
      However, in developing countries, for the children who receive cardiac surgery,
      perioperative mortality and morbidity remain high. Pediatric cardiac anesthesia
      is a specialty in its infancy worldwide, and in developing countries, it is often
      nonexistent. Visiting 'specialists' as part of medical mission teams often
      provides anesthesia, but the hope for the future is that local staff will be
      trained in pediatric cardiac anesthesia and collaborative regional cardiac
      centers will be the mainstay of care, offering safer surgery to more children.

PMID- 21199133
TI  - Towards evidence-based pharmacotherapy in children.
AB  - In daily practice, it is difficult to find a registered drug for children,
      because about 70% of the drugs prescribed in children are not studied, off-label
      or unlicensed in this age group. Clinical trials have usually been performed in
      adults, and then in daily practice dosages are adjusted for children without
      proper studies in that age group. In some countries, national formularies are
      being established to overcome the existing variance in prescribing between
      physicians. Complicating factors in finding the correct dosage for children
      include the heterogeneity between different age groups in the developmental
      stages of the organs influencing the absorption, distribution, metabolism, and
      excretion as well as differences in body composition during growth. Growth may
      also influence the effects and adverse effects of a drug used in a child. For
      oral administration of drugs in children, the bioavailability, the taste, the
      composition, and the absence of toxic ingredients for that age group are
      additional important factors. The EU has recently introduced legislation to
      stimulate the pharmaceutical industry to investigate the pharmacological effect
      and safety of new medicines in children. In response to this legislation,
      research networks are being established to provide the optimal infrastructure for
      pediatric drug investigation. The goals of this paper are to review the current
      problems in daily practice and to address the needs for evidence based
      pharmacotherapy in children.

PMID- 21199134
TI  - Pediatric regional anesthesia: what is the current safety record?
AB  - The use of regional anesthetics, whether as adjuncts, primary anesthetics or
      postoperative analgesia, is increasingly common in pediatric practice. Data on
      safety remain limited because of the paucity of very large-scale prospective
      studies that are necessary to detect low incidence events, although several
      studies either have been published or have reported preliminary results. This
      paper will review the data on complications and risk in pediatric regional
      anesthesia. Information currently available suggests that regional blockade, when
      performed properly, carries a very low risk of morbidity and mortality in
      appropriately selected infants and children.

PMID- 21199135
TI  - Tolerance and addiction; the patient, the parent or the clinician?
AB  - Tolerance has been recognized for some time where chronic exposure to certain
      drugs, particularly benzodiazepines and opioids, is associated with apparent
      tachyphylaxis. When these drugs are stopped or progressively reduced as in
      'tapering', withdrawal symptoms may result. Tolerance and the flip side of the
      coin, withdrawal, are the determinants of addiction. It is increasingly apparent
      that tolerance can occur acutely, even within the time span of a single
      anesthetic for a surgical procedure. Addiction is caused by agents, foreign to
      the body, that provoke adaptation by homeostatic biological processes. When these
      agents are withdrawn, the adaptive mechanisms, devoid of substrate, take time to
      diminish and produce symptoms recognizable under the term of 'withdrawal'.
      Children may be exposed to these agents in different ways; in utero, as a result
      of substances that the mother ingests by enteral, parenteral or inhalational
      means that are transmitted to the infant via the placenta; as a result of an
      anesthetic for surgery; or as a result of sedation and analgesia administered to
      offset the stresses and trauma inherent from intensive care treatment in the
      neonatal intensive care unit or pediatric intensive care unit. Additionally,
      anesthetic and intensive care staff are exposed to powerful and addictive drugs
      as part of everyday practice, not simply by overt access, but also by subliminal
      environmental exposure.

PMID- 21199136
TI  - Sexually transmitted infections among female sex workers in Hong Kong: the role
      of migration status.
AB  - OBJECTIVES: Female sex workers (FSW) have been considered reservoirs and vectors
      of sexually transmitted infections (STI) in the community. This study estimated
      the prevalence of STI/human immunodeficiency virus (HIV) among FSW of various
      migration and residential status in Hong Kong and identified possible risk
      factors. METHODS: An outreach "Well-women" clinic was set up at Ziteng, a non
      governmental organization working with FSW. Details of their lifestyle and health
      risk behavior were gathered before screening tests were performed, and the data
      were analyzed according to their place of origin. RESULTS: A total of 503 FSW
      were screened for STI/HIV between 2005 and 2007. Syphilis, gonorrhea, chlamydia,
      and HIV accounted for 1.8, 1.8, 4.6, and 0.2%, respectively. After adjusting for
      confounders, having >= 2 sexual partners (odds ratio [OR] 8.33, 95%CI: 2.17
      33.46), residence status (OR 0.38, 95%CI: 0.17-0.89), and daily frequency of
      douching (OR 3.02, 95%CI: 1.23-7.35) were identified as significant predictors.
      CONCLUSIONS: This study provides important insights on the screening and
      associated risk factors of STI among FSW working in Hong Kong. The contextual
      factors identified reflect the social and geographical context in which these
      women are operating and how they protect their health using their own means.
      These findings encourage policymakers and health professionals to redirect their
      focus and resources to a more holistic approach to sexual health when planning
      and implementing effective STI/HIV prevention programs.

PMID- 21199137
TI  - Description and burden of travel-related cases caused by enteropathogens reported
      in a Canadian community.
AB  - BACKGROUND: Risk of infections by enteropathogens among individuals traveling
      outside their country of residence is considered important. Such travel-related
      cases (TRC) have been poorly estimated and described in Canada. METHODS: Data
      from an enhanced, passive surveillance system of diseases caused by
      enteropathogens within a Canadian community from June 2005 to May 2009 were used
      to describe TRC in terms of disease (pathogen, symptoms, hospitalization,
      duration, and timing of sickness relative to return); demographics (age and
      gender); and travel (destination, length, and accommodation); and to compare them
      with non-TRC. RESULTS: Among 1,773 reported cases, 446 (25%) were classified as
      TRC with 9% of them being new immigrants. The main TRC diseases were
      campylobacteriosis, salmonellosis, and giardiasis. Disease onset occurred before
      return in 42% of TRC. Main destinations were Latin America/Caribbean and Asia. No
      differences by month and year were observed for onset, departure, and return
      dates. In addition to new immigrants, three subgroups of TRC based on travel
      destination, length of travel, type of accommodation, and age were identified and
      some diseases were more frequently observed in these subgroups. Generally, TRC
      did not differ from domestic cases in terms of age, gender, symptoms,
      hospitalization, and disease duration. Campylobacter coli and Salmonella
      enteritidis were significantly more frequent among TRC. CONCLUSIONS: TRC of
      diseases caused by enteropathogens that are reportable in Canada represent a
      significant proportion of the burden of the total diseases. Subgroups of TRC
      exist and are associated with certain diseases. These results help inform the
      assessment of the actual risk related to travel for each subgroup of travelers
      and quantify the attribution of traveling abroad to the overall burden of these
      gastrointestinal diseases.

PMID- 21199138
TI  - A comparison of pharmacist travel-health specialists' versus primary care
      providers' recommendations for travel-related medications, vaccinations, and
      patient compliance in a college health setting.
AB  - BACKGROUND: Pretravel medication and vaccination recommendations and receipt were
      compared between primary care providers (PCPs) without special training and
      clinical pharmacists specializing in pretravel health. METHODS: A retrospective
      chart review of patients seen for pretravel health services in a pharmacist-run
      travel clinic (PTC) compared to PCPs at a University Student Health Center.
      Vaccine/medication recommendations were assessed for consistency with
      national/international guidelines. Medical/pharmacy records were queried to
      determine the receipt of medications/vaccinations. RESULTS: The PTC recommended
      antibiotics for travelers' diarrhea were given more often when indicated (96% vs
      50%, p < 0.0001), and patients seen in the PTC received their medications more
      often (75% vs 63%, p = 0.04). PCPs prescribed more antibiotics for travelers'
      diarrhea that were inconsistent with guidelines (not ordered when indicated 49%
      vs 6%, p < 0.0001 and ordered when not indicated 21% vs 3%, p < 0.0001). The PTC
      prescribed antimalarials more often when indicated (98% vs 81%, p < 0.0001),
      while PCPs prescribed more antimalarials that were inconsistent with guidelines
      (not ordered when indicated 15% vs 1%, p < 0.0001 and ordered when not indicated
      19% vs 2%, p < 0.0001). The PTC ordered more vaccines per patient when indicated
      (mean = 2.77 vs 2.31, p = 0.0012). PTC patients were more likely to receive
      vaccines when ordered (mean = 2.38 vs 1.95, p = 0.0039). PCPs recommended more
      vaccines per patient that were inconsistent with guidelines (not ordered when
      indicated: mean = 0.78 vs 0.12, p < 0.0001, ordered when not indicated: mean 0.18
      vs 0.025, p < 0.0001). CONCLUSIONS: A pharmacist-run pretravel health clinic can
      provide consistent evidence-based care and improve patient compliance compared to
      PCPs without special training. Pretravel health is a dynamic and specialized
      field that requires adequate time, resources, and expertise to deliver the best
      possible care.

PMID- 21199139
TI  - Histoplasmosis and paracoccidioidomycosis in a non-endemic area: a review of
      cases and diagnosis.
AB  - BACKGROUND: Histoplasmosis and paracoccidioidomycosis (PCM) have increased in
      Spain in recent years, due firstly to the migration from endemic regions and
      secondly to travelers returning from these regions. In non-endemic areas,
      diagnosis of both diseases is hampered by the lack of experience, long silent
      periods, and the resemblance to other diseases such as tuberculosis and
      sarcoidosis. METHODS: A total of 39 cases of imported histoplasmosis and 6 cases
      of PCM diagnosed in the Spanish Mycology Reference Laboratory since 2006 were
      analyzed. Microbiological diagnosis was performed using classical methods and
      also a specific real-time polymerase chain reaction (RT-PCR) assay for each
      microorganism. RESULTS: We had 9 cases of probable histoplasmosis in travelers
      and 30 cases in immigrants, 29 of whom were defined as proven.
      Paracoccidioidomycosis (PCM) cases were either immigrants or people who had lived
      for a long period of time in endemic regions, all of whom were classified as
      proven cases. Cultures showed a good sensitivity in detecting Histoplasma
      capsulatum in immigrants with proven histoplasmosis (73%); however, growth was
      very slow. The fungus was never recovered in traveler patients. Paracoccidioides
      brasiliensis was isolated in a culture only in one case of the proven PCM.
      Serological methods were not very reliable in immunocompromised patients with
      histoplasmosis (40%). A PCR-based technique for histoplasmosis detected 55.5% of
      the cases in travelers (probable cases) and 89% of the cases in immigrants
      (proven). The PCR method for PCM detected 100% of the cases. CONCLUSIONS: These
      kinds of mycoses are increasingly frequent in non-endemic areas, and newer and
      faster techniques should be used to reach an early diagnosis. The RT-PCR
      techniques developed appear to be sensitive, specific, and fast and could be
      helpful to detect those mycoses. However, it is also essential that physicians
      perform differential diagnosis in individuals coming from endemic areas.

PMID- 21199140
TI  - Travel-related mosquito-transmitted disease questionnaire survey among health
      professionals in Taiwan.
AB  - BACKGROUND: Health-care professionals can help travelers by providing accurate
      pre-travel counseling for mosquito-transmitted diseases such as malaria, yellow
      fever, and dengue fever. Governments and international organizations will benefit
      from knowledge survey among health professionals in this field to promote the
      development of travel health profession. This study investigates physicians' and
      nurses' knowledge regarding malaria, yellow fever, and dengue fever. METHODS: A
      cross-sectional questionnaire survey was distributed to physicians and nurses in
      Taiwan interested in travel medicine between April and September of 2008. The
      self-administered, single-choice questionnaire evaluated knowledge regarding
      epidemiology, prophylactic medication for malaria, yellow fever, and dengue
      fever, and vaccinations for yellow fever as well as background information of
      participants. RESULTS: Complete information was collected from 82 physicians and
      203 nurses. (Out of 289, effective response rate = 99.9%). The mean percentage of
      accurate responses was similar for all three diseases: malaria 67.3% (range,
      16.8%-90.5%); yellow fever 65.4% (39.6%-79.3%); and dengue fever 74.4% (14.4%
      96.5%). The items with the lowest accuracy were (1) behavior of the dengue fever
      vector Aedes aegypti mosquito (14.4%) and (2) incubation period of malaria
      (16.8%). There were 60.4% participants who did not know the current revaccination
      interval for the yellow fever vaccine. The average knowledge scores for all three
      diseases were statistically significantly higher in the physician group.
      CONCLUSIONS: Analysis of the results revealed significant deficits in travel
      medicine knowledge among health-care providers. Emphasis on continuing medical
      education for disease vector behavior, prophylactic drug prescription, and
      preventative vaccination is important to travel safety. Health professionals in
      Taiwan should actively participate in the International Society of Travel
      Medicine to follow the international standard of travel medicine practitioners.
      This type of survey should be adopted in other countries which would be helpful
      in improving the quality of care for travelers.

PMID- 21199141
TI  - Standardized training in nurse model travel clinics.
AB  - BACKGROUND: International travel plays a significant role in the emergence and
      redistribution of major human diseases. The importance of travel medicine clinics
      for preventing morbidity and mortality has been increasingly appreciated,
      although few studies have thus far examined the management and staff training
      strategies that result in successful travel-clinic operations. Here, we describe
      an example of travel-clinic operation and management coordinated through the
      University of Utah School of Medicine, Division of Infectious Diseases. This
      program, which involves eight separate clinics distributed statewide, functions
      both to provide patient consult and care services, as well as medical provider
      training and continuing medical education (CME). METHODS: Initial training, the
      use of standardized forms and protocols, routine chart reviews and monthly
      continuing education meetings are the distinguishing attributes of this program.
      An Infectious Disease team consisting of one medical doctor (MD) and a physician
      assistant (PA) act as consultants to travel nurses who comprise the majority of
      clinic staff. RESULTS: Eight clinics distributed throughout the state of Utah
      serve approximately 6,000 travelers a year. Pre-travel medical services are
      provided by 11 nurses, including 10 registered nurses (RNs) and 1 licensed
      practical nurse (LPN). This trained nursing staff receives continuing travel
      medical education and participate in the training of new providers. All nurses
      have completed a full training program and 7 of the 11 (64%) of clinic nursing
      staff serve more than 10 patients a week. Quality assurance measures show that
      approximately 0.5% of charts reviewed contain a vaccine or prescription error
      which require patient notification for correction. CONCLUSION: Using an initial
      training program, standardized patient intake forms, vaccine and prescription
      protocols, preprinted prescriptions, and regular CME, highly trained nurses at
      travel clinics are able to provide standardized pre-travel care to international
      travelers originating from Utah.

PMID- 21199142
TI  - Travelers' thrombosis--a state of practice in Germany.
AB  - BACKGROUND: Evidence-based guidelines to prevent travelers' thrombosis (TT) are
      still missing. We wanted to know whether travelers perceive the risk of TT, how
      they and their physicians cope with this in daily life, and whether recommended
      thrombosis prophylaxis (TP) was actually performed. METHODS: A standardized
      questionnaire (Q1) asking for age, gender, travel habits, and the assessment of
      the risk of TT was given to randomly incoming travelers seeking for travel
      medicine advice prior to long haul travel. A second questionnaire (Q3) focusing
      on the actually performed TP was answered by these travelers after return. The
      physician assessed travelers' thrombosis risk (TR) and gave specific
      recommendations for TP in questionnaire Q2. Besides analysis of age, gender, the
      awareness of the risk of TT, travelers' TR, duration, and kind of travel, we
      compared performed and recommended TP and analyzed the influence of relevant
      factors on TP. RESULT: A total of 315 travelers (43.3% male, aged 43.2 +/- 15.9
      y) took part in this survey. We received responses from 275, 309, and 248
      travelers who answered Q1, Q2, and Q3, respectively. Travelers (91.6%) were aware
      of the risk of TT which was significantly higher among travelers aged 60 years
      and older. Travelers' TR had a significant influence on recommended and performed
      TP (p < 0.001). We found a moderate agreement between recommended and performed
      TP (kappa coefficient = 0.54). More travelers than recommended performed a
      specific TP (49.6% vs 39.8%) which was mainly done by the intake of
      acetylsalicylic acid (ASA). CONCLUSIONS: Travelers are well aware of the risk of
      TT and are compliant to perform at least the recommended TP for which physicians
      predominantly consider travelers' TR. The high rate of non-recommended intake of
      ASA and the different dosage regimes recommended for TP with ASA or heparin,
      however, indicate the need of better information for travelers and physicians.

PMID- 21199143
TI  - Protective measures against acute respiratory symptoms in French pilgrims
      participating in the Hajj of 2009.
AB  - Among a cohort of 274 French pilgrims participating in the 2009 Hajj, 77.4% used
      hand disinfectant, 89.8% used disposable handkerchiefs, and 79.6% used face
      masks; 97.4% were vaccinated against seasonal flu, 5.8% against H1N1, and 31.4%
      against pneumococcus. Influenza vaccine and face mask use did not significantly
      reduce respiratory symptoms.

PMID- 21199144
TI  - Campylobacter jejuni is not an important pathogen as a cause of diarrhea in US
      travelers to Mexico.
AB  - Campylobacter jejuni is an unusual cause of travelers' diarrhea acquired in
      Mexico, but previous studies have relied only on stool culture for diagnosis. We
      conducted a cohort study to determine if antibody seroconversion to C jejuni
      would better reflect the occurrence of infection acquired in Mexico. Serum IgG,
      IgA, and IgM antibodies to Campylobacter seroconverted in only 2 of 353
      participants (0.6%). These data further support that C jejuni infection is an
      unusual cause of travelers' diarrhea in US visitors to Mexico.

PMID- 21199145
TI  - An unusual case of hypereosinophilia and abdominal pain: an outbreak of
      Trichostrongylus imported from New Zealand.
AB  - We report an outbreak of severe symptomatic Trichostrongylus spp. in travelers
      visiting a sheep farm in New Zealand. The unusual source of the outbreak was
      traced as the use of sheep manure as an organic fertilizer on a salad garden.

PMID- 21199146
TI  - Fluke infertility: the late cost of a quick swim.
AB  - Schistosomiasis in the returning traveler is closely associated with fresh water
      exposure in sub-Saharan Africa and is commonly asymptomatic. We describe two
      patients who presented with unusual gynecological presentations of
      schistosomiasis many years after travel to endemic areas. The manifestations of
      female genital schistosomiasis are discussed.

PMID- 21199147
TI  - Study of the genetic discrimination between imported and autochthonous cases of
      malaria in South Korea.
AB  - There has been a great increase of Plasmodium vivax incidences in the Republic of
      Korea and the genetic diversity of the parasite became more complex with the
      rapid dissemination of newly introduced genotypes. Surveillance of imported
      malaria is very important, but there is no good way to determine imported vs.
      internal cases. In this study, we characterized imported vivax cases, analyzed
      the genetic sequence of three imported vivax malaria cases for the merozoite
      surface protein-1 (MSP-1) and circumsporozoite protein (CSP) genes, and clearly
      discriminated an imported vivax case that was misdiagnosed as indigenous by
      genetic analysis. PCR reaction for the merozoite surface protein-1 (MSP-1) and
      circumsporozoite protein (CSP) genes from three imported vivax cases were
      amplified and sequenced. The genetic variations were compared with a previously
      constructed database of South Korean isolates. The imported vivax cases showed
      various patterns on incubation period before onset. Most cases were from other
      parts of Asia. The MSP-1 gene sequence analysis of three imported cases showed
      that the imported cases had completely different sequences from any subtypes from
      Korean isolates. Case-1 and Case-2 exact match with an Indian isolate, and Case-3
      had great similarity with isolates from countries neighboring Indonesia. CSP gene
      analysis based on the repeat patterns showed similar results that the sequences
      from the imported cases well matched with the patient's traveled countries and
      completely discriminated with indigenous cases. AMA-1 gene analysis also
      supported these results. We were able to clearly distinguish three imported vivax
      cases from indigenous by using a genetic database of Korean isolates and were
      able to suspect its origin by genotyping. This study demonstrated the usefulness
      of genetic survey on imported malaria cases.

PMID- 21199148
TI  - Contact dermatitis after temporary tattoo at Sharm El Sheik.

PMID- 21199149
TI  - Lymphedema in a Guyanan migrant.

PMID- 21199150
TI  - Travel during pandemic (H1N1) 2009.

PMID- 21199152
TI  - Oral mucosa as a source of Mycobacterium leprae infection and transmission, and
      implications of bacterial DNA detection and the immunological status.
AB  - Leprosy is an important health problem in Brazil despite extensive use of
      multidrug therapy. The nasal mucosa is the preferential site of entry and exit of
      Mycobacterium leprae, and although lesions have been found in the oral mucosa,
      its potential involvement in the transmission of leprosy bacilli has never been
      investigated. We investigated the presence of the M. leprae DNA in buccal swabs
      of leprosy patients (334) and household contacts (1288) through polymerase chain
      reaction (PCR), and correlated this with clinical and laboratorial evaluations.
      The overall positivity for patients and contacts was 18.26% and 6.83%,
      respectively. Subclinical infection among contacts was considered when PCR and
      anti-PGL-1 ELISA presented positive results. This study provides evidence that
      the oral mucosa may be a secondary site of M. leprae transmission and infection,
      and contacts with bacillary DNA may be actively involved in transmission. We have
      also shown that bacilli DNA is more frequently found in the oral mucosa of PB
      patients. Our findings have great epidemiological relevance and indicate an
      additional strategy for leprosy control programmes and dental clinics.

PMID- 21199153
TI  - Sometimes they come back--the return of influenza.

PMID- 21199154
TI  - Zygomycosis in Europe: analysis of 230 cases accrued by the registry of the
      European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis
      between 2005 and 2007.
AB  - Zygomycosis is an important emerging fungal infection, associated with high
      morbidity and mortality. The Working Group on Zygomycosis of the European
      Confederation of Medical Mycology (ECMM) prospectively collected cases of proven
      and probable zygomycosis in 13 European countries occurring between 2005 and
      2007. Cases were recorded by a standardized case report form, entered into an
      electronic database and analysed descriptively and by logistic regression
      analysis. During the study period, 230 cases fulfilled pre-set criteria for
      eligibility. The median age of the patients was 50 years (range, 1 month to 87
      years); 60% were men. Underlying conditions included haematological malignancies
      (44%), trauma (15%), haematopoietic stem cell transplantation (9%) and diabetes
      mellitus (9%). The most common manifestations of zygomycosis were pulmonary
      (30%), rhinocerebral (27%), soft tissue (26%) and disseminated disease (15%).
      Diagnosis was made by both histology and culture in 108 cases (44%). Among 172
      cases with cultures, Rhizopus spp. (34%), Mucor spp. (19%) and Lichtheimia
      (formerly Absidia) spp. (19%) were most commonly identified. Thirty-nine per cent
      of patients received amphotericin B formulations, 7% posaconazole and 21%
      received both agents; 15% of patients received no antifungal therapy. Total
      mortality in the entire cohort was 47%. On multivariate analysis, factors
      associated with survival were trauma as an underlying condition (p 0.019),
      treatment with amphotericin B (p 0.006) and surgery (p <0.001); factors
      associated with death were higher age (p 0.005) and the administration of
      caspofungin prior to diagnosis (p 0.011). In conclusion, zygomycosis remains a
      highly lethal disease. Administration of amphotericin B and surgery, where
      feasible, significantly improve survival.

PMID- 21199155
TI  - Identification of Anaplasma phagocytophilum in tick populations in Estonia, the
      European part of Russia and Belarus.
AB  - Anaplasma phagocytophilum is associated with diseases of goats, sheep, cattle,
      dogs and horses. In the beginning of the 1990s it was identified as a human
      pathogen, causing human granulocytic anaplasmosis (HGA) in the USA, Europe and
      the far east of Russia. A. phagocytophilum is maintained in nature in an enzootic
      cycle including ticks as the main vector and a wide range of mammalian species as
      reservoirs. Ixodes ricinus and I. persulcatus ticks were collected in Estonia,
      Belarus and the European part of Russia and screened for the presence of A.
      phagocytophilum by real-time PCR. Positive samples were found only among I.
      ricinus, in 13.4% in the European part of Russia, 4.2% in Belarus, 1.7% in
      mainland Estonia and 2.6% on Saaremaa Island. Positive samples were sequenced for
      partial 16S rRNA, groESL and ankA genes and phylogenetic analyses were performed.
      The results showed that A. phagocytophilum circulating in Eastern Europe belongs
      to different groESL lineages and 16S rRNA gene variants and also consists of
      variable numbers of repetitive elements within the ankA gene.

PMID- 21199156
TI  - Alteration in the phenotype of macrophages in the repair of renal interstitial
      fibrosis in mice.
AB  - AIM: Renal interstitial fibrosis is the final common pathway determining long
      term prognosis of chronic kidney diseases, but its repair process is scarcely
      understood. Because recent reports indicate that M2 macrophages play important
      roles in the repair of various tissues, special attention was paid to the
      phenotypes of infiltrating macrophages in the present study when the histological
      changes occurring in mouse kidneys after the release of unilateral ureteral
      obstruction (UUO) inducing renal fibrosis were analyzed. METHODS: The left ureter
      of male mice was obstructed for 10 days by using a vascular clamp, and that
      kidney was removed for analysis either on the day when the clamp was removed or
      after the kidney had been allowed to recover for 3, 7 or 21 days. RESULTS:
      Interstitial fibrosis assessed by picrosirius red staining decreased with time
      after the release, and this decrease was paralleled by a decrease in the
      interstitial area positive for alpha-smooth muscle actin. Macrophage infiltration
      assessed by F4/80 staining also significantly decreased from day 3. In contrast,
      real-time reverse transcription polymerase chain reaction revealed that the
      ratios of mRNA for the macrophage scavenger receptor (CD204) and the mannose
      receptor (CD206), both of which are preferentially expressed on M2 macrophages,
      to CD68 (a general macrophage marker) were significantly greater on day 7 than on
      day 0 in the UUO-released mice. CONCLUSION: Although the total number of
      infiltrating myofibroblasts and macrophages decreased after UUO release, the
      ratios of macrophages expressing CD204 and CD206 increased, suggesting that M2
      macrophages play an important role in the repair of renal fibrosis.

PMID- 21199157
TI  - Abstracts of the 15th Congress of the Asian Pacific Society of Respirology,
      November 22-25 2010. Manila, Philippines.

PMID- 21199158
TI  - Cellular therapies for lung disease: a distant horizon.
AB  - Lung diseases constitute a major global burden of health and are characterized by
      inflammation and chronic fibrosis resulting in a loss of gas exchange units. To
      date there has been no effective treatment to reverse these chronic inflammatory
      changes and tissue remodelling. Recently, stem cells have been shown to
      successfully treat animal models of lung disease. In addition, certain cells have
      demonstrated a capacity to differentiate into lung cells. Based on these
      preliminary data, there are clinical trials underway to examine the potential for
      cellular therapies in lung disease. Recently, there have been a variety of cell
      examined for both their immunomodulatory effects on the lung as well as their
      potential for differentiation into lung cells. These range from lung progenitor
      cells, circulating cells, mesenchymal stem cells (MSCs), induced pluripotent stem
      cells (iPS), placental stem cells and embryonic stem cells (ESCs). Several cell
      types demonstrate immunomodulatory effects including circulating cells, MSCs and
      placental stem cells. In addition, iPS, placental cells and ESCs have shown some
      capacity for differentiation. Despite these major steps forward cellular therapy
      for lung diseases still faces challenges. Issues that need to be resolved include
      bioethical issues, the safety of cell transplantation, ideal routes of delivery,
      the timing and the specific indications that would make cellular therapy
      effective.

PMID- 21199159
TI  - Functional haplotypes in the PTGDR gene fail to associate with asthma in two
      Australian populations.
AB  - BACKGROUND AND OBJECTIVE: Haplotypes in the promoter region of the prostanoid DP
      receptor (PTGDR) gene have been shown to functionally influence gene
      transcription and to be associated with asthma in two previous case-control
      studies in Caucasians. This study tested the association of PTGDR haplotypes with
      asthma phenotypes in two large Caucasian-Australian populations. These results
      were incorporated in a meta-analysis with previously published data to determine
      the overall role for these haplotypes in the risk of asthma. METHODS: Three PTGDR
      promoter-region single nucleotide polymorphisms (SNP) were genotyped in 368
      individuals from the Western Australian Twin Child Health study and 2988
      individuals from the Busselton Health Study. Logistic regression and transition
      disequilibrium tests were used to assess whether SNP genotypes and three SNP
      haplotypes were associated with doctor-diagnosed asthma or intermediate
      quantitative traits. Longitudinal data from the Busselton Health Study were used
      to examine whether PTGDR influences changes in lung function over time. Meta
      analysis incorporated the findings of this study with those of two previous
      studies in Caucasian populations. RESULTS: Cross-sectional associations between
      PTGDR haplotypes and asthma phenotypes were non-significant (P > 0.05) in both
      populations. Longitudinal analyses of PTGDR and lung function were also non
      significant. Meta-analysis, however, suggested that haplotype TCT was
      significantly associated with decreased risk of asthma (OR = 0.76; P = 0.02)
      while haplotype CCC was not significantly associated with asthma (OR = 1.30; P =
      0.07). CONCLUSIONS: These results suggest that despite the non-significant
      findings in the present study populations, PTGDR promoter haplotypes may account
      for a small but significant proportion of the risk of asthma in Caucasian
      populations.

PMID- 21199160
TI  - Rhinovirus infection induces expression of airway remodelling factors in vitro
      and in vivo.
AB  - BACKGROUND AND OBJECTIVE: A hallmark of asthma is airway remodelling, which
      includes increased deposition of extracellular matrix (ECM) protein. Viral
      infections may promote the development of asthma and are the most common causes
      of asthma exacerbations. We evaluated whether rhinovirus (RV) infection induces
      airway remodelling, as assessed by ECM deposition. METHODS: Primary human
      bronchial epithelial cells and lung parenchymal fibroblasts were infected with RV
      2 or RV-16, or treated with RV-16 RNA, imiquimod (Toll-like receptor (TLR) 7/8
      agonist) or polyinosinic : polycytidylic acid (poly I : C) (activator of TLR 3,
      retinoic-acid-inducible protein I and melanoma-differentiated-associated gene 5).
      Changes in ECM proteins and their transcription were measured by ELISA and
      quantitative real-time PCR. In addition, gene expression for ECM proteins was
      assessed in a mouse model of RV infection. RESULTS: RV infection increased
      deposition of the ECM protein, perlecan, by human bronchial epithelial cells, and
      collagen V and matrix-bound vascular endothelial growth factor were increased in
      both human bronchial epithelial cell and fibroblast cultures. Purified RV-16 RNA,
      poly I : C and imiquimod induced similar increases in ECM deposition to those
      observed with RV-infected fibroblasts. However, only poly I : C induced ECM
      deposition by bronchial epithelial cells, suggesting that RV-induced ECM
      deposition is mediated through TLR. Furthermore, gene expression for fibronectin
      and collagen I was increased in lung homogenates of mice infected with RV-1b.
      CONCLUSIONS: RV infection and TLR ligands promote ECM deposition in isolated cell
      systems and RV induces ECM gene expression in vivo, thus demonstrating that RV
      has the potential to contribute to remodelling of the airways through induction
      of ECM deposition.

PMID- 21199161
TI  - The value of computed tomography scanning for the detection of coronary artery
      disease in patients with idiopathic pulmonary fibrosis.
AB  - BACKGROUND AND OBJECTIVE: Patients with idiopathic pulmonary fibrosis (IPF) have
      a higher prevalence of coronary artery disease and this could have an impact on
      their outcomes. We investigated the predictive ability of coronary artery
      calcification, assessed by routine CT, which may predict the presence of coronary
      artery disease. METHODS: The study cohort consisted of patients with IPF and with
      left heart catheterization data plus CT scans from July 2003 to July 2008. Grades
      of coronary calcification on CT were compared with left heart catheterization
      determination of coronary artery disease. RESULTS: There were 57 patients in whom
      left heart catheterization review demonstrated significant coronary artery
      disease in 28.1% (16/57), mild disease in 40.3% (23/57) and none in 31.6%
      (18/57). The median time interval between the catheterization and the reviewed CT
      scan was 39 days. The sensitivity of moderate to severe calcification for
      significant coronary artery disease was 81%, while the specificity was 85%, with
      an associated odds ratio of 25.2 (4.64-166, P < 0.005). There was excellent
      agreement among three radiologists in the grading of coronary calcification.
      CONCLUSIONS: Coronary calcification, as assessed by routine CT of the chest, has
      very good performance characteristics in predicting underlying significant
      coronary artery disease in patients with IPF. The routine availability of this
      study enables the ready screening for coronary artery disease in IPF patients.

PMID- 21199162
TI  - Cigarette smoke modulates PGE(2) and host defence against Moraxella catarrhalis
      infection in human airway epithelial cells.
AB  - BACKGROUND AND OBJECTIVE: Airway bacterial infections pose a significant
      challenge to the management of COPD, a disease mainly caused by cigarette
      smoking. However, the mechanisms of impaired airway mucosal innate immunity
      against bacteria in COPD remain unclear. We examined the effect of cigarette
      smoke on prostaglandin E(2) (PGE(2)) and downstream epithelial host defence
      mechanisms including the antimicrobial substance human beta-defensin-2 (hBD-2).
      METHODS: Brushed bronchial epithelial cells were obtained from healthy smokers
      and individuals with COPD, and cultured under air-liquid interface conditions
      with or without exposure to whole cigarette smoke (WCS) or Moraxella catarrhalis
      (Mc) infection. Bacterial load, hBD-2 (a molecule known to kill Mc) and PGE(2)
      were measured. RESULTS: WCS decreased Mc-induced hBD-2 expression and increased
      Mc load on bronchial epithelial cells from healthy smokers and COPD patients.
      Moreover, WCS inhibited PGE(2) induction following Mc. PGE(2) was shown to
      increase hBD-2 production in bronchial epithelial cells from healthy smokers, but
      not from COPD patients. CONCLUSIONS: The results suggest that in well
      differentiated human bronchial epithelial cells, WCS may impair host defence
      against Mc in part through inhibiting PGE(2) production.

PMID- 21199163
TI  - Effect of early pulmonary rehabilitation on health care utilization and health
      status in patients hospitalized with acute exacerbations of COPD.
AB  - BACKGROUND AND OBJECTIVE: Acute exacerbations of chronic obstructive pulmonary
      disease (AECOPD) incur heavy utilization of health-care resources for patients
      who require hospitalization. We evaluated whether an early outpatient pulmonary
      rehabilitation programme (PRP) after hospitalization for AECOPD could reduce
      acute health-care utilization over the succeeding year. METHODS: Sixty patients
      admitted with AECOPD were randomized to either PRP or usual care (UC). The PRP
      group received 8weeks of outpatient rehabilitation programme 2-3weeks after
      discharge from hospital. Lung function, 6min walk test and dyspnoea score were
      assessed at baseline, 3, 6, 9 and 12months, while St George's respiratory
      questionnaire and cardiopulmonary exercise test were assessed at baseline, 3, 6
      and 12months. RESULTS: The PRP and UC groups demonstrated a 53.3% and 43.3% risk
      of readmissions at 12months (incident risk ratio 0.97 (95% CI: 0.57-1.60),
      P=0.90). The mean readmission rates were 1.00+/-1.20 and 1.03+/-1.87 (P=0.47) for
      the PRP versus UC groups respectively. The rates of AECOPD and emergency
      department visits were similar between the two groups. The St George's
      respiratory questionnaire total score was lower in the PRP group (40.15+/-19.10
      vs 46.91+/-18.21, P=0.01 and 42.3+/-20.06 vs 51.44+/-18.98 P=0.01 at 3 and
      6months respectively). There were no statistically significant differences in the
      FEV(1) % predicted, dyspnoea score, 6min walk test and maximal oxygen consumption
      during exercise test between PRP and UC at different time points. CONCLUSIONS: An
      early rehabilitation programme following AECOPD led to improvement in quality of
      life up to 6months, but did not reduce health-care utilization at 1year.

PMID- 21199164
TI  - Sarcoidosis: lost in translation.

PMID- 21199165
TI  - Maternal psychosocial factors around delivery, and the behavior of 2-year-old
      children.
AB  - BACKGROUND: The objectives of the present study were to explore whether maternal
      psychosocial factors, mental health and work stress around delivery, are related
      to the behavior of 2-year-old children. METHODS: In a prospective cohort study
      design, pregnant women attending the National Taiwan University Hospital for
      delivery and post-partum care from April 2004 to January 2005 were recruited and
      their children were observed at 24 months. A total of 186 mother-term-born child
      dyads completed the measurement. The five-item Mental Health Index (MHI-5) self
      report data of maternal psychosocial factors were selected from the Taiwanese
      version of the short form 36 (SF-36). The Child Behavior Checklist for age 11/2-5
      (CBCL/11/2-5) was completed by the parents when the child was 2 years old.
      RESULTS: The mean score of mental health around delivery was 68.11. The
      proportion of mothers with work stress seldom and always was 61.8% and 24.7%,
      respectively. The mean of the total CBCL score, and internalizing, externalizing
      behavior and sleep problems scores was 45.95, 11.89, 15.59 and 4.23,
      respectively. After adjusting for the potential confounders, maternal work stress
      around delivery was found to have a significant effect on the total CBCL and
      externalizing, attention and aggressive, behavioral problems of 2-year old
      children. Maternal mental health around delivery, however, did not show
      significant effects on child behavior. CONCLUSIONS: Work stress around delivery
      seems to aggravate children's externalizing behavior problems at 2 years old. It
      is therefore important to improve the psychosocial health and reduce the stress
      of pregnant women.

PMID- 21199167
TI  - Sleep characteristics of young children in Japan: internet study and comparison
      with other Asian countries.
AB  - BACKGROUND: A recent international Internet-based study of young children (birth
      to 36 months) found that total sleep duration in Japan was the shortest among 17
      countries/regions. The present study compared features of children's sleep in
      Japan relative to those in other Asian countries/regions. METHODS: Parents of 872
      infants and toddlers in Japan (48.6% boys), and parents of 20 455 infants and
      toddlers in 11 other Asian countries/regions (48.1% boys; China, Hong Kong,
      India, Indonesia, Korea, Malaysia, Philippines, Singapore, Taiwan, Thailand, and
      Vietnam) completed an Internet-based expanded version of the Brief Infant Sleep
      Questionnaire. RESULTS: Young children in Japan exhibited significantly fewer
      nocturnal wakings and shorter daytime sleep in comparison with other Asian
      countries/regions. Although the former finding was apparent in all age groups,
      the reduced duration of daytime sleep in Japan was not present until after 3
      months of age. Interestingly, sleep problems were reported by significantly fewer
      parents in Japan compared with those in other Asian countries/regions, although
      parents in Japan reported significantly more difficulty at bedtime. CONCLUSIONS:
      The short sleep duration of young children in Japan is largely due to a
      relatively short duration of daytime sleep. Significant differences in sleep
      characteristics in Japan relative to other Asian regions were found primarily
      after 3 months of age. Future studies should further explore the underlying
      causes and the potential impacts of these sleep differences.

PMID- 21199168
TI  - Factors associated with hypoxemia in children infected with pandemic H1N1 2009
      influenza virus.
AB  - BACKGROUND: Hypoxemia was found to be a major cause of death from pandemic H1N1
      2009 influenza (pH1N1) infection. There are limited data on factors associated
      with hypoxemia in children infected with pH1N1 influenza virus. METHODS: Factors
      associated with hypoxemia were investigated using univariate and multivariate
      analysis in 76 hospitalized pediatric patients with laboratory-confirmed H1N1
      influenza virus infection at Gyeongsang National University Hospital in Jinju,
      South Korea, from August 2009 to January 2010 by retrospective chart review.
      RESULTS: Hypoxemia occurred in 17 children (22%), of whom three were admitted to
      an intensive care unit and one died. Hypoxemic patients were significantly more
      likely to have a higher respiratory rate, pulse rate, white blood cell count
      (WBC), and C-reactive protein level, as well as a longer hospital stay.
      Respiratory rate and WBC count at admission were independently associated with
      hypoxemia as determined on multivariate analysis, and this association was found
      to be clinically significant. CONCLUSION: Although a higher WBC count and
      respiratory rate may not be specific for pHINI but represent the degree of
      disease severity for any infectious respiratory disease in general, clinicians
      can use these parameters at admission as useful, early indicators of disease
      severity in pediatric pH1N1 infection.

PMID- 21199169
TI  - New cancer treatment strategy using combination of green tea catechins and
      anticancer drugs.
AB  - Green tea is now recognized as the most effective cancer preventive beverage. In
      one study, 10 Japanese-size cups of green tea daily supplemented with tablets of
      green tea extract limited the recurrence of colorectal polyps in humans to 50%.
      Thus, cancer patients who consume green tea and take anticancer drugs will have
      double prevention. We studied the effects of combining (-)-epigallocatechin
      gallate (EGCG) and anticancer drugs, focusing on inhibition of cell growth and
      induction of apoptosis. Numerous anticancer drugs, such as tamoxifen, COX-2
      inhibitors, and retinoids were used for the experiments, and the combination of
      EGCG and COX-2 inhibitors consistently induced the enhancement of apoptosis. To
      study the mechanism of the enhancement, we paid special attention to the enhanced
      expressions of DDIT3 (growth arrest and DNA damage-inducible 153, GADD153),
      GADD45A, and CDKN1A (p21/WAF1/CIP1) genes, based on our previous evidence that a
      combination of EGCG and sulindac specifically induced upregulated expression of
      GADD153 and p21 genes in PC-9 lung cancer cells. The synergistic enhancements of
      apoptosis and GADD153 gene expression in human non-small cell lung cancer cells
      by the combination of EGCG and celecoxib were mediated through the activation of
      the MAPK signaling pathway. This article reviews the synergistic enhancement of
      apoptosis, gene expression, and anticancer effects using various combinations of
      EGCG and anticancer drugs, including the combination of (-)-epicatechin (EC) and
      curcumin. Based on the evidence, we present a new concept: green tea catechins as
      synergists with anticancer drugs.

PMID- 21199170
TI  - Plasma biomarker discovery and validation for colorectal cancer by quantitative
      shotgun mass spectrometry and protein microarray.
AB  - The development of a new plasma biomarker for early detection would be necessary
      to improve the overall outcome of colorectal cancer. Here we report the
      identification and validation of the ninth component of complement (C9) as a
      novel plasma biomarker for colorectal cancer by cutting-edge proteomic
      technologies. Plasma proteins were enzymatically digested into a large array of
      peptides, and the relative quantity of a total of 94,803 peptide peaks was
      compared between 31 colorectal cancer patients and 59 age/sex-matched healthy
      controls using 2D image-converted analysis of liquid chromatography and mass
      spectrometry. The selected biomarker candidates were validated in 345 subjects
      (115 colorectal cancer patients and 230 age/sex-matched healthy controls) using
      high-density reverse-phase protein microarrays. Plasma levels of Apo AI and C9 in
      colorectal cancer patients significantly differed from healthy controls with P
      values of 7.94*10(-4) and 1.43*10(-12) (Student's t-test), respectively. In
      particular, C9 was elevated in patients with colorectal cancer, including those
      with stage-I and -II diseases (P=3.01*10(-3) and P=1.13*10(-5) , respectively).
      Although the significance of the present study must be validated in an
      independent clinical study, the increment of plasma C9 may be applicable to the
      early detection of colorectal cancer.

PMID- 21199172
TI  - Fermentation of starch stimulates propagated contractions in the human colon.
AB  - BACKGROUND: In healthy humans, up to 30 g of daily ingested starch escape small
      intestinal digestion, and are fermented in the colon. This physiological starch
      malabsorption could modify colonic motility through metabolites such as short
      chain fatty acids produced by fermentation. METHODS: Ten healthy volunteers
      swallowed a probe, consisting of an infusion catheter, six perfused catheters and
      a balloon connected to a barostat. On two consecutive days colonic motility was
      recorded in fasting subjects in the basal state (1 h), and then during (3 h), and
      after (2 h) the intracolonic infusion of 750 mL of isoosmotic and isovolumetric
      solutions containing sodium chloride with or without 15 g wheat starch. We
      determined (i) the volume of hydrogen and methane exhaled in breath, (ii) a
      global motility index and the number of high amplitude propagated contractions
      (HAPCs), and (iii) the mean balloon volume, reflecting the tonic motor activity.
      KEY RESULTS: [median (IQR)] Compared to the basal period, colonic infusion of
      starch or saline did not modify the colonic motility index and tone. However, the
      number of HAPCs was significantly higher during and after infusion of starch than
      of saline [4.5 (2.75-6.5) vs 0.96 (0-2.66)/5 h, starch vs saline respectively; P
      = 0.011]. CONCLUSIONS & INFERENCES: In healthy humans, colonic fermentation of a
      physiological malabsorbed amount of starch has no effect on the tonic and phasic
      colonic motor activities, but produces a significant increase in the number of
      HAPCs. This may participate in the physiological propulsion of colonic contents.

PMID- 21199173
TI  - Gastrointestinal dysmotility is associated with altered gut flora and septic
      mortality in patients with severe systemic inflammatory response syndrome: a
      preliminary study.
AB  - BACKGROUND: The gut is an important target organ for injury after severe insult,
      and resolution of feeding intolerance is crucial for critically ill patients. We
      investigated gut flora and motility to evaluate the impact of gastrointestinal
      dysmotility on septic complications in patients with severe systemic inflammatory
      response syndrome (SIRS). METHODS: Sixty-three ICU patients with severe SIRS were
      divided into two groups depending on their intestinal condition. Patients with
      feeding intolerance comprised patients who had feeding intolerance, defined as >=
      300 mL reflux from nasal gastric feeding tube in 24 h, and patients without
      feeding intolerance comprised patients with no feeding intolerance. We compared
      fecal microflora, incidences of bacteremia, and mortality between these groups.
      KEY RESULTS: Analysis of feces showed that patients with feeding intolerance had
      significantly lower numbers of total obligate anaerobes including Bacteroidaceae
      and Bifidobacterium, higher numbers of Staphylococcus, lower concentrations of
      acetic acid and propionic acid, and higher concentrations of succinic acid and
      lactic acid than those in patients without feeding intolerance (P <= 0.05).
      Patients with feeding intolerance had higher incidences of bacteremia (86%vs 18%)
      and mortality (64%vs 20%) than did patients without feeding intolerance (P <=
      0.05). CONCLUSIONS & INFERENCES: Gut flora and organic acids were significantly
      altered in patients with severe SIRS complicated by gastrointestinal dysmotility,
      which was associated with higher septic mortality in SIRS patients.

PMID- 21199174
TI  - High-resolution esophageal pressure topography is superior to conventional sleeve
      manometry for the detection of transient lower esophageal sphincter relaxations
      associated with a reflux event.
AB  - BACKGROUND: Transient lower esophageal sphincter relaxations (TLESRs) are the
      main mechanism underlying gastro-esophageal reflux and are detected during
      manometric studies using well defined criteria. Recently, high-resolution
      esophageal pressure topography (HREPT) has been introduced and is now considered
      as the new standard to study esophageal and lower esophageal sphincter (LES)
      function. In this study we performed a head-to-head comparison between HREPT and
      conventional sleeve manometry for the detection of TLESRs. METHODS: A setup with
      two synchronized MMS-solar systems was used. A solid state HREPT catheter, a
      water-perfused sleeve catheter, and a multi intraluminal impedance pH (MII-pH)
      catheter were introduced in 10 healthy volunteers (M6F4, age 19-56). Subjects
      were studied 0.5 h before and 3 h after ingestion of a standardized meal.
      Tracings were blinded and analyzed by the three authors according to the TLESR
      criteria. KEY RESULTS: In the HREPT mode 156 TLESRs were scored, vs 143 during
      sleeve manometry (P = 0.10). Hundred and twenty-three TLESRs were scored by both
      techniques. Of all TLESRs (177), 138 were associated with reflux (78%). High
      resolution esophageal pressure topography detected significantly more TLESRs
      associated with a reflux event (132 vs 119, P = 0.015) resulting in a sensitivity
      for detection of TLESRs with reflux of 96% compared to 86% respectively. Analysis
      of the discordant TLESRs associated with reflux showed that TLESRs were missed by
      sleeve manometry due to low basal LES pressure (N = 5), unstable pharyngeal
      signal (N = 4), and residual sleeve pressure >2 mmHg (N = 10). CONCLUSIONS &
      INFERENCES: The HREPT is superior to sleeve manometry for the detection of TLESRs
      associated with reflux. However, rigid HREPT criteria are awaited.

PMID- 21199175
TI  - Influence of the 5-HT3 receptor antagonist ondansetron on gastric sensorimotor
      function and nutrient tolerance in healthy volunteers.
AB  - BACKGROUND: Serotonin is believed to be involved in the regulation of the gastric
      accommodation reflex in man however which receptor subtype(s) are involved
      remains to be elucidated. METHODS: Eleven healthy subjects (nine men, age 19-30)
      underwent a gastric barostat and a drinking test after treatment with either
      placebo or ondansetron (8 mg intravenously). During the barostat protocol an
      intragastric flaccid bag was stepwise distended (2 mmHg increments 2 min) to
      determine gastric compliance and sensitivity to distention. Subsequently, the
      pressure level was set at intra-abdominal pressure +2 mmHg while volume was
      followed before and after administration of a liquid meal (200 mL; 300 kcal).
      During the drink test volunteers drank at a rate of 15 mL min(-1) until maximal
      satiation. Results (mean +/- SEM) were compared using t-tests and mixed model
      analysis. KEY RESULTS: Gastric compliance was not significantly altered by
      ondansetron (51.5 +/- 5.6 vs 49.2 +/- 5.2 mL mmHg(-1)), neither were the pressure
      thresholds for first perception or discomfort. Ondansetron treatment did not
      affect basal gastric tone (173 +/- 14 vs 156 +/- 12 mL), neither did it affect
      the amplitude of the meal-induced relaxation (160 +/- 52 vs 131 +/- 43 mL) or the
      maximum volume increase after the meal (264 +/- 54 mL vs 234 +/- 51 mL). During
      the drinking test the amount of liquid meal ingested at maximum satiation was
      significantly increased by ondansetron (784 +/- 74 vs 907 +/- 64 mL, P < 0.05).
      CONCLUSIONS & INFERENCES: These data suggest that 5-HT acting at 5-HT(3)
      receptors is not involved in the control of gastric sensorimotor function, but
      contributes to the regulation of hunger and satiation in man.

PMID- 21199176
TI  - Postnatal intestinal engraftment of prospectively selected enteric neural crest
      stem cells in a rat model of Hirschsprung disease.
AB  - BACKGROUND: Identification of neuronal progenitor/stem cells in the postnatal gut
      suggests the development of transplantation approaches to enteric nervous system
      (ENS) diseases. Many clinical applications would require engrafting large
      segments of postnatal gut in vivo. We investigated the ability of unselected gut
      cells vs selected enteric neural crest stem cells (eNCSCs) to engraft and
      differentiate in the postnatal gut in the Hirschsprung disease (HD, ednrb(sl/sl))
      rat. METHODS: Total intestinal cells or eNCSCs (alpha(4) integrin(+), p75(++))
      from embryonic day (E)14.5 rats carrying a marker transgene (human placental
      alkaline phosphatase, hPAP) were injected intraperitoneally (i.p.) into neonatal
      HD rats and their healthy littermates. The entire gut was systematically analyzed
      3 weeks later for hPAP(+) cells between the serosal surface and the muscularis
      mucosae. Engrafted cells were examined for HuC/D, S-100B, neuropeptide Y (NPY),
      neuronal nitric oxide synthase (nNOS), and vasoactive intestinal peptide (VIP)
      expression. KEY RESULTS: No rats (0/33) injected with unselected cells had
      hPAP(+) cells in the ENS that expressed neuronal or glial markers. 5/11 healthy
      and 4/5 HD rats injected with eNCSCs showed widespread but low density
      engraftment in the ENS with cells expressing neuronal or glial markers. Neurons
      expressed nNOS and VIP. There was no engraftment in the colon of either HD or
      wildtype rats. CONCLUSIONS & INFERENCES: Enteric neural crest stem cells will
      engraft diffusely throughout the postnatal gut of HD rats and differentiate into
      neurons and glia. Engraftment is not uniform, likely related to age-dependent
      changes in the gut mesenchyme. Intraperitoneal injection is easily performed in
      sick neonates and may be developed as a technique to supply exogenous ENS cells
      to the diseased postnatal gut.

PMID- 21199177
TI  - Abstracts of the 14th Congress of the EFNS (European Federation of Neurological
      Societies). Geneva, Switzerland. September 26-28, 2010.

PMID- 21199179
TI  - LRRK2 as a therapeutic target in Parkinson's disease.

PMID- 21199180
TI  - The possible risk of cancer in patients with MS: a controversial issue.

PMID- 21199181
TI  - Hippocampal cavities are not associated with cognitive impairment in transient
      global amnesia.
AB  - BACKGROUND: Hippocampal sulcal cavities (HSC) have been speculated to contribute
      to a higher vulnerability of memory pathways and might be a possible etiological
      factor in transient global amnesia (TGA). Therefore, we evaluated the influence
      of HSC on cognitive long-term outcome in TGA-patients. METHODS: Fourteen
      otherwise healthy patients with the clinical syndrome of TGA in their history
      underwent a high-resolution magnetic resolution imaging and a comprehensive
      neuropsychological test battery. The neuropsychological control group consisted
      of 15 healthy subjects and was balanced for age, sex and other risk factors as
      well as intellectual and social status. RESULTS: Magnetic resolution imaging and
      neuropsychological testing have been performed 1128 days (median) after the TGA.
      HSC have been detected in nine of the 14 patients and have been bilateral in
      eight of them. There were no differences in cognitive performance in patients
      with and without HSC as well as compared to healthy subjects. Even in patients
      with greater lesion load, only a slight visuospatial deficit was found.
      CONCLUSIONS: Although an increased incidence of HSCs is detected in TGA patients,
      cavities are not obligatorily in TGA. Moreover, even patients with hippocampal
      cavities achieve a full neuropsychological recovery independent of the frequency
      and size of the hippocampal lesions.

PMID- 21199182
TI  - Non-anti-MAG DADS neuropathy as a variant of CIDP: clinical,
      electrophysiological, laboratory features and response to treatment in 10 cases.
AB  - BACKGROUND AND PURPOSE: Some patients within the spectrum of chronic inflammatory
      demyelinating polyradiculoneuropathies (CIDP) have distal acquired demyelinating
      symmetric (DADS) neuropathy, usually associated with anti-myelin-associated
      glycoprotein (MAG) IgM monoclonal gammopathy. The aim of this retrospective study
      was to investigate patients with DADS neuropathy without anti-MAG antibodies, and
      study their response to immunotherapy. METHODS: Patients were selected on the
      basis of (i) 'Definite CIDP' according to the EFNS/PNS Guideline criteria, (ii)
      The presence of disproportionately prolonged motor latencies resulting in a
      terminal latency index (TLI) <= 0.25 in at least two motor nerves and (iii) The
      absence of anti-MAG antibodies on ELISA. Response to immunotherapy was defined as
      persistent improvement by at least one point on the INCAT disability score.
      RESULTS: Data from 146 CIDP patients were analysed, and 10 patients were
      included. Six had clinically pure sensory neuropathy, and four had sensorimotor
      neuropathy. Ataxia was present in nine patients, generalized areflexia in seven
      and postural tremor in two. Five of the 10 patients had abnormal sensory
      potentials only in the upper limbs. An associated condition was found in nine
      patients: two chronic lymphocytic leukaemias, four IgG monoclonal gammopathies
      (one associated with non-Hodgkin's lymphoma) and two IgM monoclonal gammopathies
      of unknown significance. Patients were mostly improved with intravenous
      immunoglobulin (IVIg), corticosteroids, plasma exchanges, or a combination
      thereof. CONCLUSION: DADS neuropathy without anti-MAG antibodies is more likely
      to be considered a variant of CIDP. In addition, such patients should be
      systematically investigated for an associated haematological or immunological
      condition.

PMID- 21199183
TI  - Health care situation of patients with relapsing-remitting multiple sclerosis
      receiving immunomodulatory therapy: a retrospective survey of more than 9000
      German patients with MS.
AB  - BACKGROUND AND PURPOSE: First-line immunomodulatory treatment with interferon
      beta or glatiramer acetate is accepted as effective basic therapy in patients
      with relapsing-remitting multiple sclerosis (RRMS). However, a considerable
      portion of patients does not benefit from treatment. METHOD: To test basic
      immunomodulatory treatment under real-life conditions, we retrospectively
      analyzed clinical and subclinical disease activity within the last 12 months in a
      cohort of 9916 patients with RRMS, of which 7896 patients were receiving
      immunomodulatory treatment. In addition, factors associated with treating
      physicians' consideration of a switch of current treatment were assessed.
      RESULTS: The majority of treated patients (approximately 66%) experienced no
      relapse during the last 12 months. However, in line with common clinical study
      findings, about one-third (approximately 34%) of patients had relapses. When MRI
      data were taken into account, approximately one-quarter (24%) of patients would
      qualify for therapy escalation to monoclonal antibody natalizumab. Relapse rate
      in the preceding year (the year directly prior to the start of retrospective data
      collection) was strongly associated with considering a switch of current
      treatment. In addition, therapy switch was more often considered in younger
      patients. The relationship between MRI findings in the absence of clinical
      symptoms and consideration of a treatment switch was not as clear. CONCLUSIONS:
      This analysis confirms that disease progression occurs in a considerable
      proportion of patients with RRMS. These patients should be considered for therapy
      escalation.

PMID- 21199184
TI  - Liver toxicity possibly related with ropinirole use in the treatment of restless
      legs syndrome.

PMID- 21199186
TI  - Haemophilia 2011.

PMID- 21199187
TI  - Successful use of recombinant FVIIa in combined factor V and FVIII deficiency
      with surgical bleeding resistant to substitutive treatment. A case report.

PMID- 21199188
TI  - A comparison between two semi-quantitative bleeding scales for the diagnosis and
      assessment of bleeding severity in type 1 von Willebrand disease.

PMID- 21199185
TI  - Socio-demographic and clinical factors influencing the adherence to treatment in
      Parkinson's disease: the ADHESON study.
AB  - BACKGROUND: Symptoms of Parkinson's disease (PD) are usually controlled by a
      continuous titration of medication and addition of multiple therapies over the
      course of the disease. Therapeutic complex schemes, polymedication, comorbidities
      and the number of medications required contribute to non-adherence. METHODS: This
      cross-sectional survey was performed in 418 patients with PD on treatment with
      any antiparkinsonian medication. Patient adherence was assessed through
      physicians' subjective perception and the Morisky-Green test (MGT). Several
      social, demographic and clinical features were correlated through bivariate and
      multivariate analyses. RESULTS: According to the physician's opinion 93.7%, and
      according to the MGT 60.4% of patients were adherent to parkinsonian therapy. The
      bivariate analysis showed greater adherence in patients with a high level of
      knowledge about the disease (62.8%), good clinical control (63.6%), a spouse or
      life partner (63%) and higher incomes (66%). Negative correlation with
      psychiatric symptoms was found. In relation to the MGT, the logistic regression
      model showed a negative correlation between cognitive deterioration and
      psychiatric pathology and adherence to therapy. CONCLUSIONS: The physician's
      impression overestimated the compliance of patients when compared with an
      objective evaluation such as the MGT. Cognitive impairment and psychiatric
      symptoms are the clinical variables associated with a lower level of adherence.

PMID- 21199189
TI  - Development of a protocol for the quantitative determination of HBeAg using the
      Elecsys(r) HBeAg immunoassay.
AB  - Loss of hepatitis 'e' antigen (HBeAg) in patients with HBeAg-positive chronic
      hepatitis B is associated with improved long-term clinical outcome and is defined
      as a goal of antiviral treatment by clinical practice guidelines. Recent studies
      suggest that baseline levels and on-treatment monitoring of HBeAg levels may
      identify patients most likely to respond to therapy. The aim of this study was
      the development of a protocol for the quantitative determination of HBeAg using
      the Elecsys(r) HBeAg immunoassay. The linear range of the Elecsys(r) HBeAg
      immunoassay was established using recombinant HBeAg and five different diluents.
      The assay was validated against the Paul Ehrlich Institute (PEI) international
      standard serum. Linearity was demonstrated up to a cut-off index (COI) of 1000,
      independent of the diluent used. Optimal linearity was obtained using the
      Elecsys(r) Universal Diluent. Using the PEI reference standard, conversion
      factors were established as 4.50 COI for 1 PEIU/mL corresponding to 0.222 PEIU/mL
      for a COI of 1. Based on the results from these analyses, a simple algorithm for
      the quantitative measurement of HBeAg using the Elecsys(r) HBeAg immunoassay was
      developed. Using a simple algorithm with an initial 1:40 dilution, the Elecsys(r)
      HBeAg assay provides robust quantification of serum HBeAg in an easy-to-use and
      rapid system. The use of a commercially available, standardized diluent improves
      comparability between laboratories.

PMID- 21199190
TI  - Transcription factors CgUPC2A and CgUPC2B regulate ergosterol biosynthetic genes
      in Candida glabrata.
AB  - Zn[2]-Cys[6] binuclear transcription factors Upc2p and Ecm22p regulate the
      expression of genes involved in ergosterol biosynthesis and exogenous sterol
      uptake in Saccharomyces cerevisiae. We identified two UPC2/ECM22 homologues in
      the pathogenic fungus Candida glabrata which we designated CgUPC2A and CgUPC2B.
      The contribution of these two genes to sterol homeostasis was investigated. Cells
      that lack CgUPC2A (upc2ADelta) exhibited enhanced susceptibility to the sterol
      biosynthesis inhibitors, fluconazole and lovastatin, whereas upc2BDelta-mutant
      cells were as susceptible to the drugs as wild-type cells. The growth of
      upc2ADelta cells was also severely attenuated under anaerobic conditions.
      Lovastatin treatment enhanced the expression of ergosterol biosynthetic genes,
      ERG2 and ERG3 in wild-type and upc2BDelta but not in upc2ADelta cells. Similarly,
      serum-induced expression of ERG2 and ERG3 was completely impaired in upc2ADelta
      cells but was unaffected in upc2BDelta cells, whereas serum-induced expression of
      the sterol transporter gene CgAUS1 was impaired in both upc2ADelta and upc2BDelta
      cells. These results suggest that in C. glabrata CgUPC2A but not in CgUPC2B is
      the main transcriptional regulator of the genes responsible for maintaining
      sterol homeostasis as well as susceptibility to sterol inhibitors.

PMID- 21199191
TI  - RE1-silencing transcription factor (REST) and REST-interacting LIM domain protein
      (RILP) affect P19CL6 differentiation.
AB  - During cardiac development, the heart produces the atrial natriuretic peptide
      (ANP) and brain natriuretic peptide (BNP). These peptides are found in high
      levels in cardiomyocytes and, like a number of other embryonic genes, are up
      regulated in both failing and hypertrophied ventricles. At the transcriptional
      level, BNP and ANP genes are regulated through RE1 regulatory element, which
      binds RE1-silencing transcription factor (REST). REST/NRSF-interacting LIM domain
      protein (RILP) is required for the nuclear targeting and function of REST. In
      this study, the role of RILP and REST in cardiomyocyte development using a model
      system was studied by analyzing the expression of RILP and REST as well as
      several cardiac-specific genes during P19CL6 cell differentiation. Effects of
      RILP overexpression and transcriptional regulation of RILP in differentiating
      P19CL6 cells were also studied. RILP expression is transiently reduced during
      P19CL6 cell differentiation; however, REST expression remains unchanged. This
      transient reduction in RILP expression correlates with de-repression of
      sarcomeric myosin heavy chain, a marker for cardiomyocyte differentiation.
      Reporter gene analysis shows that RILP gene is down-regulated through 5'
      regulatory elements before cardiac-specific gene expression. These results
      suggest that RILP expression and function control REST action more so than does
      REST expression and is an important regulatory role in cardiomyocyte
      differentiation.

PMID- 21199192
TI  - Fission yeast ATF/CREB family protein Atf21 plays important roles in production
      of normal spores.
AB  - Activating transcription factor/cAMP response element binding protein (ATF/CREB)
      family transcription factors play central roles in maintaining cellular
      homeostasis. They are activated in response to environmental stimuli, bind to CRE
      sequences in the promoters of stress-response genes and regulate transcription.
      Although ATF/CREB proteins are widely conserved among most eukaryotes, their
      characteristics are highly diverse. Here, we investigated the functions of a
      fission yeast ATF/CREB protein Atf21 to find out its unique properties. We show
      that Atf21 is dispensable for the adaptive response to several stresses such as
      nitrogen starvation and for meiotic events including nuclear divisions. However,
      spores derived from atf21Delta mutants are not as mature as wild-type ones and
      are unable to form colonies under nutrition-rich conditions. Furthermore, we
      demonstrate that the Atf21 protein, which is scarce in early meiosis, gradually
      accumulates as meiosis proceeds; it reaches maximum levels approximately 8 h
      after nitrogen starvation and is present during germination. These results
      suggest that Atf21 is expressed and functions long after nitrogen starvation.
      Given that other well-characterized fission yeast ATF/CREB proteins Atf1 and Pcr1
      accumulate and function promptly upon exposure to environmental stresses, we
      propose that Atf21 is a distinct member of the ATF/CREB family in fission yeast.

PMID- 21199194
TI  - Haematological and biochemical reference intervals for infants and children in
      Gabon.
AB  - OBJECTIVES: To establish reference intervals for major haematological and
      biochemical parameters in Gabonese infants and children. METHODS: The reference
      sample population consisted of 226 healthy infants (4-9 weeks of age) and 185
      healthy children (18-60 months of age). Basic red cell parameters as well as
      total and differential white blood cell counts were performed. Clinical chemistry
      parameters consisted of glutamate-pyruvic transaminase and creatinine, and total
      bilirubin was measured in children. Statistical analysis was based on the
      guidelines of the Clinical and Laboratory Standards Institute. Nonparametric
      methods were used to determine 95% reference limits and their 90% confidence
      intervals. RESULTS:   Compared to European populations, values for several red
      cell parameters (haemoglobin, haematocrit, red blood cell count, mean corpuscular
      volume) were lower and platelet counts were higher. Eosinophils were higher in
      the older age group, most likely caused by intestinal helminths. CONCLUSIONS: The
      study confirms the importance of establishing reference limits for local
      populations. The reference ranges could be used as a benchmark for similar
      populations in Central Africa.

PMID- 21199193
TI  - Evidence for a role of angiopoietin-like 7 (ANGPTL7) in extracellular matrix
      formation of the human trabecular meshwork: implications for glaucoma.
AB  - The trabecular meshwork tissue controls the drainage of the aqueous humor of the
      eye. A dysfunctional trabecular meshwork leads to an altered fluid resistance,
      which results in increased intraocular pressure (IOP). IOP is the major risk
      factor of glaucoma, the second-leading cause of blindness in the developed world.
      In the search for genes altered by glaucomatous insults, we identified
      angiopoietin-like7 (ANGPTL7), a member of the ANGPTL family. Although
      structurally related to the angiopoietins, ANGPTL7's function is poorly
      understood. Because ANGPTL7 is secreted and because extracellular matrix (ECM)
      deposition and organization is critical for aqueous humor resistance, we
      investigated the effect of ANGPTL7 on relevant trabecular meshwork ECM genes and
      proteins. We find that overexpression of ANGPTL7 in primary human trabecular
      meshwork cells altered the expression of fibronectin, collagens type I, IV & V,
      myocilin, versican, and MMP1. ANGPTL7 also interfered with the fibrillar assembly
      of fibronectin. Finally, we find that silencing ANGPTL7 during the glucocorticoid
      insult significantly affected the expression of other steroid-responsive
      proteins. These results indicate that ANGPTL7 modulates the trabecular meshwork's
      ECM as well as the response of this tissue to steroids. Together with previous
      findings, these properties strengthen ANGPTL7's candidacy for the regulation of
      IOP and glaucoma.

PMID- 21199195
TI  - Diagnostic delay amongst tuberculosis patients in Jogjakarta Province, Indonesia
      is related to the quality of services in DOTS facilities.
AB  - OBJECTIVES: To understand determinants of care-seeking patterns and diagnostic
      delay amongst tuberculosis (TB) patients diagnosed at direct observed treatment
      short course (DOTS) facilities in Jogjakarta, Indonesia. METHODS: Cross-sectional
      survey amongst newly diagnosed TB patients in 89 DOTS facilities whose history of
      care-seeking was reconstructed through retrospective interviews gathering data on
      socio-demographic determinants, onset of TB symptoms, type of health facilities
      visited, duration of each care-seeking action were recorded. RESULTS: Two hundred
      and fifty-three TB patients were included in the study whose median duration of
      patients' delay was 1 week and whose total duration of diagnostic delay was 5.4
      weeks. The median number of visits was 4. Many of the patients' socio-demographic
      determinants were not associated with the care-seeking patterns, and no socio
      demographic determinants were associated with the duration of diagnostic delay.
      More than 60% of TB patients started their care-seeking processes outside DOTS
      facilities, but the number of visits in DOTS facilities was greater during the
      overall care-seeking process. Surprisingly, patient's immediate visits to a DOTS
      facility did not correspond to shorter diagnostic delay. CONCLUSION: Diagnostic
      delay in Jogjakarta province was not associated with patients' socio demographic
      factors, but rather with the health system providing DOTS services. This suggests
      that strengthening the health system and improving diagnostic quality within DOTS
      services is now a more rational strategy than expanding the TB programme to
      engage more providers.

PMID- 21199196
TI  - Microbial community composition and dynamics in a semi-industrial-scale facility
      operating under the MixAlcoTM bioconversion platform.
AB  - AIMS: To monitor microbial community dynamics in a semi-industrial-scale
      lignocellulosic biofuel reactor system and to improve our understanding of the
      microbial communities involved in the MixAlcoTM biomass conversion process.
      METHODS AND RESULTS: Reactor microbial communities were characterized at six time
      points over the course of an 80-day, mesophilic, semi-industrial-scale
      fermentation using community qPCR and 16S rRNA tag-pyrosequencing. We found the
      communities to be dynamic, bacterially dominated consortia capable of changing
      quickly in response to reactor conditions. Clostridia- and Bacteroidetes-like
      organisms dominated the reactor communities, but ultimately the communities
      established consortia containing complementary functional capacities for the
      degradation of lignocellulosic materials. Eighteen operational taxonomic units
      were found to share strong correlations with reactor acid concentration and may
      represent taxa integral to fermentor performance. CONCLUSIONS: The results of
      this study indicate that the emergence of complementary functional classes within
      the fermentor consortia may be a trait that is consistent across scales, and they
      suggest that there may be flexibility with respect to the specific identities of
      the organisms involved in the fermentor's degradation and fermentation processes.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides new information
      regarding the composition, dynamics and potential flexibility of the microbial
      communities associated with the MixAlcoTM process and is likely to inform the
      improvement of this and other applications that employ mixed microbial
      communities.

PMID- 21199197
TI  - Gender-based cardiometabolic risk evaluation in minority and non-minority men
      grading the evidence of non-traditional determinants of cardiovascular risk.
AB  - Evaluation of cardiometabolic risk has become vital in primary prevention of
      adverse vascular events (coronary artery disease, heart attack, stroke or
      congestive heart failure), particularly in younger middle-aged men (40-60 years
      old). To discern the prevalence of events in these men, clinicians often stratify
      cardiovascular risk and treat according to traditional Framingham risk criteria.
      Yet it is evident that the traditional Framingham risk assigned to intermediate-
      and low-risk men will miss several of these individuals deemed at high
      'cardiometabolic risk', also known as residual cardiovascular risk. This review
      will elaborate the definition of cardiometabolic risk and apply the use of
      surrogate markers for cardiovascular risk stratification in men in addition to
      the traditional Framingham-based markers. It will utilise both gender non
      specific and gender-specific determinants of cardiometabolic risk. Lastly, it
      will examine minority men's health and racial differences in these determinants
      of cardiovascular risk. This analysis includes an electronic literature search
      utilising PubMed, EMBASE and MEDLINE databases to clarify the level of evidence
      for the stepwise utility of novel biomarkers for cardiometabolic risk in the male
      patient. This manuscript generates discussion of the utility of markers of
      cardiometabolic risk stratification. The following questions are summarised: (i)
      Are there non-traditional tests that might define this risk better than
      traditional markers? (ii) Will treatment based on this risk assessment augment
      present risk stratification and lower cardiovascular risk? (iii) What is known
      regarding racial differences surrounding cardiometabolic risk assessment?
      Traditional risk factors including Framingham Risk Score underestimate the
      overall 10 year and lifetime risk for the intermediate-risk younger middle-aged
      men<60 years of age. This fact is especially true in the minority population. We
      have graded the evidence of non-gender specific and gender-specific markers of
      cardiometabolic risk, thereby, allowing greater clarification of risk in this
      population. The pragmatic use of these novel markers of cardiometabolic risk may
      help stratify those individuals at greater lifetime risk than that noted by the
      Framingham Risk Score.

PMID- 21199198
TI  - Aerosolised antipsychotic assuages agitation: inhaled loxapine for agitation
      associated with schizophrenia or bipolar disorder.
AB  - OBJECTIVE: To describe the efficacy and safety of inhaled loxapine, a new
      formulation of an older antipsychotic being developed for the treatment of
      agitation associated with schizophrenia or bipolar disorder. DATA SOURCES: A
      literature search was conducted by querying http://www.pubmed.gov,
      http://www.fda.gov, http://www.accessdata.fda.gov/scripts/cder/drugsatfda and
      http://www.clinicaltrials.gov for the search terms 'loxapine' AND 'agitation',
      'inhaled loxapine', 'staccato loxapine'. The manufacturer was asked to provide
      copies of posters presented at national and international meetings, and to
      provide any copies of papers currently in press. STUDY SELECTION: All available
      reports of studies were identified. DATA EXTRACTION: Descriptions of the
      principal results and calculation of number needed to treat (NNT) and number
      needed to harm (NNH) for relevant dichotomous outcomes were extracted from the
      study reports. DATA SYNTHESIS: Inhaled loxapine is delivered using a handheld
      device that produces a thermally generated condensation aerosol free of
      excipients or propellants. Time to maximum plasma concentration is approximately
      2 min. In two phase III studies (one in subjects with schizophrenia, the other in
      subjects with bipolar disorder) inhaled loxapine 5 and 10 mg were both superior
      to placebo as early as 10 min after administration, as measured using the
      Positive and Negative Syndrome Scale excited component. Pooling together data
      from three efficacy studies, NNT for response for inhaled loxapine 5 or 10 mg vs.
      placebo were 4 (95% CI 3-5) and 3 (95% CI 3-4), respectively, with response
      defined as achieving a Clinical Global Impressions - Improvement score of 1 or 2
      at 2 h postdose. This effect size is in the range observed for intramuscular
      administration of other antipsychotics for agitation associated with
      schizophrenia or bipolar disorder. There were no clinically relevant signals for
      the emergence of extra-pyramidal side effects or akathisia. The most commonly
      encountered adverse event appears to be dysgeusia (distorted taste sense or bad
      taste), with a NNH vs. placebo of 10 (95% CI 7-22) or 12 (95% CI 8-26), for
      loxapine 10 or 5 mg, respectively. CONCLUSIONS: Inhaled loxapine appears
      efficacious and tolerable for the treatment of agitation associated with
      schizophrenia or bipolar disorder. Although simple to self-administer, inhaled
      loxapine requires a degree of cooperation from the recipient and thus will not be
      a substitute for an injection during psychiatric emergencies when the patient is
      actively refusing medication treatment. The efficacy and safety of inhaled
      loxapine in elderly patients and in outpatient care settings remain to be
      established.

PMID- 21199199
TI  - Pharmacy users' expectations of pharmacy encounters: a Q-methodological study.
AB  - BACKGROUND: Pharmacy practice is evolving according to general health-care trends
      such as increased patient involvement and public health initiatives. In addition,
      pharmacists strive to find new professional roles. Clients' expectations of
      service encounters at pharmacies is an under-explored topic but crucial to
      understanding how pharmacy practice can evolve efficiently. OBJECTIVE: To
      identify and describe different normative expectations of the pharmacy encounter
      among pharmacy clients. METHODS: Q methodology, an approach to systematically
      explore subjectivity that retains complete patterns of responses and organizes
      these into factors of operant subjectivity. SETTING AND PARTICIPANTS: Eighty-five
      regular prescription medication users recruited at Swedish community pharmacies
      and by snowballing. RESULTS: Seven factors of operant subjectivity were
      identified, and organized into two groups. Factors that emphasized the physical
      drug product as the central object of the pharmacy encounter were labelled as
      independent drug shopping; logistics of drug distribution; and supply of
      individual's own drugs. Factors that emphasized personal support as desirable
      were labelled competence as individual support; individualist professional
      relations, just take care of me; and practical health-care and lifestyle support.
      DISCUSSION AND CONCLUSIONS: The systematic Q-methodological approach yielded
      valuable insights into how pharmacy clients construct their expectations for
      service encounters. They hold differentiating normative expectations for pharmacy
      services. Understanding these varying viewpoints may be important for developing
      and prioritizing among efficient pharmacy services. Clients' expectations do not
      correspond with trends that guide current pharmacy practice development. This
      might be a challenge for promoting or implementing services based on such trends.

PMID- 21199200
TI  - 'I'm searching for solutions': why are obese individuals turning to the Internet
      for help and support with 'being fat'?
AB  - INTRODUCTION: This study explores what types of information obese individuals
      search for on the Internet, their motivations for seeking information and how
      they apply it in their daily lives. METHOD: In-depth telephone interviews with an
      Australian community sample of 142 individuals with a BMI >= 30 were conducted.
      Theoretical, purposive and strategic samplings were employed. Data were analysed
      using a constant comparative method. RESULTS: Of the 142 individuals who
      participated in the study, 111 (78%) searched for information about weight loss
      or obesity. Of these, about three quarters searched for weight loss solutions.
      The higher the individual's weight, the more they appeared to search for weight
      loss solutions. Participants also searched for information about health risks
      associated with obesity (n = 28), how to prevent poor health outcomes (n = 30)
      and for peer support forums with other obese individuals (n = 25). Whilst
      participants visited a range of websites, including government-sponsored sites,
      community groups and weight loss companies, they overwhelmingly acted upon the
      advice given on commercial diet websites. However, safe, non-judgemental spaces
      such as the Fatosphere (online fat acceptance community) provided much needed
      solidarity and support. CONCLUSIONS: The Internet provides a convenient source of
      support and information for obese individuals. However, many turn to the same
      unsuccessful solutions online (e.g. fad dieting) they turn to in the community.
      Government and community organisations could draw upon some lessons learned in
      other consumer-driven online spaces (e.g. the Fatosphere) to provide supportive
      environments for obese individuals that resonate with their health and social
      experiences, and address their needs.

PMID- 21199201
TI  - Carnosic acid prevents obesity and hepatic steatosis in ob/ob mice.
AB  - AIM:   Carnosic acid (CA) inhibits adipogenesis in vitro. The present study
      evaluated the therapeutic effects of CA in ob/ob mice. METHODS:   The
      experimental animals were given a standard chow diet with or without CA for 5
      weeks. Bodyweight gain and food intake were measured during this period. Magnetic
      resonance imaging analysis, histological examination, serum chemistry analysis
      and intraperitoneal glucose tolerance test (IPGTT) were all performed. RESULTS:  
      The mice fed CA experienced significant weight loss and reduced visceral
      adiposity, in addition to significantly reduced serum triglyceride (TG) and
      cholesterol levels. Importantly, CA had a dramatic effect on the liver by
      reducing the hepatic TG content, thus decreasing serum alanine aminotransferase
      levels. In addition, IPGTT revealed that CA significantly improved glucose
      tolerance. CONCLUSION:   These data suggest that CA is a novel therapeutic agent
      for obesity-related non-alcoholic fatty liver disease.

PMID- 21199202
TI  - Hepatic nodular hamartoma containing liver cysts, ductal plate malformations and
      peribiliary glands.
AB  - An 83-year-old man with hepatocellular carcinoma was found to have a low-echoic
      and low-density tumor measuring 7.2 cm * 5.6 cm. Caroli's disease was absent.
      Clinical diagnosis was intrahepatic cholangiocarcinoma. Three cores of liver
      biopsy were obtained from the tumor. Histologically, it consisted of liver cysts,
      ductal plate malformations, peribiliary glands, hepatocytes, portal tracts and
      mesenchymal tissue. Apparent features of cirrhosis were not found. The liver
      cysts were lined by a layer of cuboidal cells with multiple papillary
      protrusions. The ductal plate malformations resembled fetal ductal plates. The
      peribiliary glands were seromucous glands. Immunohistochemically, these abnormal
      ductal structures showed positive reaction to biliary type cytokeratins, namely,
      cytokeratin (CK)7, CK8, CK18 and CK19. Mucin gene expression showed that these
      biliary structures are positive for fetal antigen MUC1. MUC6 is also positive in
      them. Aberrant expression of CD10 was observed in these biliary structures. MUC2,
      MUC5AC and CDX2 were negative. The author thinks that this lesion is hepatic
      hamartoma with ductal plate malformations, liver cysts and peribiliary glands. To
      the best of the author's knowledge, this type of liver nodule has not been
      reported in the published work.

PMID- 21199203
TI  - Ischemic preconditioning of the graft for intestinal transplantation in rats.
AB  - To test the hypothesis that two modalities of IPC should decrease acute rejection
      and BT after SBTx in rats. Orthotopic allogenic SBTx was performed from Wistar to
      BN. IPC was performed by 2 ' and 5 ' superior mesenteric artery clamping,
      following 2-min and 5-min reperfusion before graft cooling and retrieving. Donor
      recipient sets were randomly allocated to five groups: IPC2m4d, IPC2m7d,
      IPC5min7d, and the control groups for the two end points; ctrl4d and ctrl7d. IRI,
      rejection, and BT were assessed after four or seven days depending on the groups.
      Measured variables included: histology, leukocyte activation by tissue MPO
      determination, and proinflammatory cytokines (IL-b and TNF-alpha) to assess
      inflammatory response. Leukocyte activation was significantly reduced in IPC2m7d
      in comparison with Ctrl and IPC5min7d. Rejection tended to be lower in IPC2min7d.
      Cytokine levels were contradictory and not consistent with histology. Finally, BT
      was less frequent in IPC2min4d group but this benefit was missed in animals with
      rejection (7d). Inflammatory response (MPO) was reduced and rejection tended to
      be lower after in IPC2m7d. Bacterial translocation was reduced in IPC2min4d but
      the benefit was missed at day 7.

PMID- 21199205
TI  - The role of cytomegalovirus infection and disease in pediatric bone marrow
      transplant recipients in Mexico City in the context of viral drug resistance.
AB  - We aimed to identify those pediatric patients undergoing ABMT with CMV EOD who
      developed GCV resistance. Forty-seven patients were analyzed following ABMT.
      Prospective post-transplant CMV monitoring was performed weekly for the detection
      of viral leukocyte DNAaemia, viral plasma DNAaemia, and viral DNAuria by PCR.
      Plasma DNAaemia was confirmed from whole blood by the detection of CMV pp67 late
      mRNA using NASBA technology. In the cases of persistence of viral DNA in plasma,
      and positive viral RNA detection in blood, CMV drug resistance screening by
      comprehensive PCR-based RFLP and sequencing of the viral UL97 gene were performed
      retrospectively. Thirty of the 47 (63.82%) patients showed active CMV infection
      with 27/30 (74.4%) patients belonging to the D+R+ group and 25/30 with proven
      viral replication. In total, 2/30 (6.6%) children developed CMV pneumonia proven
      by immunohistochemistry. Screening of the viral UL97 gene revealed in one of
      these two cases (1/30, 3.3%) the simultaneous presence of two point mutations in
      codon 460 (M460V, M460I) conferring GCV resistance. The CMV seroprevalence (81%)
      and the incidence of active infection (63.8%) in Mexican children undergoing ABMT
      are very high.

PMID- 21199204
TI  - Acute rejection associated with donor-specific anti-MICA antibody in a highly
      sensitized pediatric renal transplant recipient.
AB  - Allograft rejection in HLA identical transplant recipients and in patients
      without detectable donor-specific anti-HLA antibodies has lead to the
      identification of non-HLA antigens as targets of the alloimmune response. MICA
      antigen has been recognized as an important non-HLA target in renal
      transplantation. Recent studies have shown that anti-MICA antibodies are
      associated with acute renal allograft rejection and failure. Current cross match
      procedures using donor lymphocytes fail to detect MICA antibodies. Transplant
      candidates are not routinely tested for pre-sensitization to MICA antigens nor
      are transplant donors typed for MICA alleles. Optimal classification and
      treatment of acute rejection associated with MICA antibody remains unknown. In
      this case report, we are the first to describe the clinical course and treatment
      of donor-specific MICA antibody associated with both Banff type II A ACR and AMR
      in a highly sensitized pediatric renal re-transplant recipient. This case also
      emphasizes the importance of pre-transplant screening for donor-specific MICA
      antibody especially in highly sensitized renal transplant patients.

PMID- 21199206
TI  - Brain-type natriuretic peptide correlates with right heart pressures in a cross
      section of pediatric heart transplant patients.
AB  - Serum brain-type natriuretic peptide level (BNP) correlates with hemodynamic
      parameters measured during cardiac catheterization in adult patients with heart
      failure. We sought to describe the relationship of BNP with invasive hemodynamic
      measurements and cellular rejection in children following OHT. Children
      undergoing catheterization for OHT surveillance had simultaneous measurement of
      BNP. A total of 62 subjects were studied. The median BNP was 171 pg/mL (range 19
      1130). There were significant positive correlations between BNP and mean PAP
      (R=0.33, p=0.009), RVSP (R=0.25, p=0.05), RVEDP (R=0.29, p=0.02), and mean RAP
      (R=0.39, p=0.002). Rejection grade varied from 0 to 3A (58 patients < ISHLT 3A
      and four patients >= ISHLT 3A). There was no significant difference in BNP based
      on cellular rejection grade. In a cohort of pediatric patients after heart
      transplantation, BNP correlates with direct measurements of right-sided
      pressures, but not with other hemodynamic measurements, time from transplant or
      rejection grade. This suggests that BNP may have a complimentary role in the
      monitoring of children following heart transplantation.

PMID- 21199207
TI  - Non-adherence in adolescent transplant recipients: the role of uncertainty in
      health care providers.
AB  - To optimize self-management and adherence in adolescent patients, HCPs need to
      discuss not only medical and treatment-related issues, but also general health
      and psychosocial concerns. Our study aimed to explore how the members of the
      paediatric team in our programme understand NA in adolescents, and how they
      define their own role regarding self-management education. We used a sequential
      mixed methods design and conducted a qualitative observational and in-depth
      interview study (n=22) and a quantitative descriptive study through self
      administered questionnaires (n=31). Our results show a discrepancy between the
      HCPs' understanding of the complex psychosocial factors impacting on long-term
      adherence, and their current limited practice of patient education. A number of
      uncertainties were found to explain the HCPs' perceived difficulty to engage in
      comprehensive patient education activities: uncertainty regarding (i) the health
      status of transplant recipients; (ii) a shared operational definition of
      adherence and the cause of organ rejection in some cases; (iii) the extent to
      which adherence is a shared responsibility which involves the HCPs as patient
      educators; (iv) the long-term impact of a LRD. To avoid the risk of conveying
      incongruent messages, multidisciplinary health care teams need to explicitly
      acknowledge and discuss the various areas of uncertainty, some of which are
      inherent to transplantation.

PMID- 21199208
TI  - Good outcome of kidney transplants in recipients of young donors: a NAPRTCS data
      analysis.
AB  - NAPRTCS data were analyzed to assess outcome of TX recipients from YDs (<5 yr) in
      comparison with IDs (6-35 yr) and ODs (36-55 yr). Of 9854 TX in NAPRTCS (1987
      2003), 469 were YD. Patient survival (PS) and graft survival (GS) were compared
      between DD TX after 1995; 81YD, 1324 ID, and 429 OD and eGFR were compared among
      functioning grafts (YD 31, ID 439, OD 174) at three yr. PS was comparable in all
      groups; GS at one, two, and three yr in TX of YD (91.1%, 83.8%, 79.7%), ID
      (93.5%, 89.7%, 83.6%), and OD (92.2%, 87.2%, 82.4%) was comparable. The eGFR in
      YD was comparable to ID but better than OD (86.5 vs. 79.7 vs. 67.2 mL/min/1.73
      m2, p 0.139 and<0.0003). Primary graft non-function was more frequent in TX from
      YD than ID and OD (3.7% vs. 0.3 and 0.7%, p=0.004); the incidence of vascular
      thrombosis was similar. The aforementioned data show that pediatric recipients of
      YD had equivalent patient and graft survival. Although primary graft non-function
      was higher, eGFR of functioning grafts was comparable to ID. With further
      improvements in care, kidneys from YD may present a viable option for
      transplantation.

PMID- 21199209
TI  - Interventional radiology for hepatic artery complications soon after living donor
      liver transplantation in a neonate.
AB  - Early hepatic artery complications after liver transplantation in children,
      having undergone LDLT, can directly affect graft and recipient outcomes, making
      early diagnosis and treatment essential. In the past, laparotomy (thrombectomy or
      reanastomosis) was generally employed to treat early hepatic artery
      complications. Recently, favorable outcomes of IR have been reported. In
      children, however, the number of such reports is small. To the best of our
      knowledge, there is no published report on IR applied to neonates with early
      hepatic artery complications. We recently succeeded in safely using IR for a
      neonate with early hepatic artery complications after LDLT and obtained a
      favorable outcome. This case is presented herein.

PMID- 21199210
TI  - Donor-specific HLA antibodies in paediatric cardiac transplant recipients are
      associated with poor graft survival.
AB  - There is increasing evidence that DSA are associated with poor graft survival,
      although there are little data in children. We aimed to describe the incidence of
      DSA in this group and to determine correlation with graft survival. HLA
      antibodies were analysed in 59 paediatric cardiac transplant recipients. Mean age
      10.4 (0.7-18.5) yr, mean time post-transplant 5.1 (0.3-17.3) yr. Antibody
      detection/identification was performed on the Luminex platform with subsequent
      identification using Lifescreen Identification kits/One-Lambda Single antigen
      kits. Forty patients (69%) had no HLA antibodies. DSA were found in four (7%).
      One had transient Class I antibodies and normal cardiac function. The other three
      had persistent Class II antibodies (two subsequently required re-transplantation,
      the third had cardiac failure due to CAV). Non-DSA were found in 15 (25%), all
      with normal graft function and without rejection. There was no difference in
      function or CAV prevalence between those with non-DSA and those without
      antibodies. HLA DSA is uncommon in paediatric cardiac allograft recipients but,
      if persistent, suggests poorer prognosis. In our series, antibodies to HLA class
      II on donor tissue were associated with increased graft loss. Routine screening
      and regular testing are recommended.

PMID- 21199211
TI  - Bone mineral disease in children after renal transplantation in steroid-free and
      steroid-treated patients--a prospective study.
AB  - Bone disease may persist after transplantation. Different approaches aiming to
      ameliorate this problem have been investigated. The aim of the study was to
      compare the long-term effect of three medical interventions: (i) two prophylactic
      oral doses of 50 mg ibandronate; (ii) daily oral dose of 0.25 MUg of 1alpha-OHD3
      (both of these regimens in patients receiving steroids), and (iii) steroid
      minimization immunosuppressive protocol in patients with no other specific
      prophylaxis. PATIENTS: A total of 37 children, at a mean age of 13.33+/-3.49 yr,
      dialyzed for 15.93+/-16.7 months before transplantation, were divided into three
      groups, depending on medical intervention. Bone mineral content and density (BMC,
      BMD, DXA), serum markers of bone resorption and formation (CTX, P1NP), calcium,
      phosphate, 25OHD3/1.25 (OH)2D3 and PTH concentration were evaluated during two yr
      of follow-up. The mean values of BMD in the whole population and among the three
      subgroups remained within the age- and gender-matched normal range during follow
      up. PATIENTS from groups II (alphacalcidiol) and III (steroid minimization)
      showed a significant decrease in BMD Z-scores over time, and this effect was
      determined with increasing age using multivariate analysis. PATIENTS receiving
      two doses of ibandronate maintained unchanged Z-scores for BMD and BMC over time.

PMID- 21199213
TI  - Visuospatial impairment in children and adolescents after liver transplantation.
AB  - A minority of children with liver transplants exhibit significant delay in global
      intelligence; others have specific learning disabilities. More specific data on
      neurocognitive strengths and weaknesses are lacking. Eighteen children aged 7-16
      yr, who had undergone LTx in Finland participated in the study. They were
      assessed on an average 7.6 (s.d. 4.5, range 1.0-15.0) years post-operatively at a
      mean age of 11.8 (s.d. 3.1, range 7.2-16.1). A standardized test of intelligence
      (WISC-III), a neuropsychological test battery (NEPSY-II), and a parental
      questionnaire on the child's development (FTF) were administered. The
      neuropsychological test profile of the LTx group was compared with that of a
      matched control group of healthy children. The LTx children achieved on an
      average normal FSIQ 94.0 and VIQ 99.6. Their Performance Intelligence Quotient
      (PIQ 88.9, p=0.043) was, however, significantly lower than the population mean.
      On neuropsychological assessment, the LTx children scored generally lower than
      the control group (p=0.004), a difference significant in sub-tests assessing
      visuospatial and visuoconstructive functions and social perception. No
      differences emerged in sub-tests of attention and executive functions, memory and
      learning, or language functions. LTx children are at increased risk for
      impairment in the visuospatial domain.

PMID- 21199212
TI  - Mortality of biliary atresia in children not undergoing liver transplantation in
      the Netherlands.
AB  - In order to further improve the outcome of BA, we characterized the mortality of
      BA patients who did not undergo OLT in the Netherlands, and compared our results
      with international data. For this purpose, we analyzed the causes of mortality of
      non-transplanted BA patients before the age of five yr, using the NeSBAR
      database. To evaluate trends in mortality, we compared the cohort 1987-1996
      (n=99) with 1997-2008 (n=111). We compared clinical condition at OLT assessment
      with available international data, using the PELD-score. Mortality of non
      transplanted BA children was 26% (26/99) in 1987-1996 and 16% (18/111) in 1997
      2008 (p=0.09). Sepsis was the prevailing direct cause of death (30%; 13/44). PELD
      scores at the time of assessment were higher in non-transplanted BA patients
      (median 20.5; range 13-40) compared with international data (mean/median between
      11.7 and 13.3). Based on our national data, we conclude that pretransplant
      mortality of BA patients is still considerable, and that sepsis is a predominant
      contributor. Our results strongly indicate that the prognosis of patients with BA
      in the Netherlands can be improved by earlier listing of patients for OLT and by
      improving pretransplant care.

PMID- 21199215
TI  - Cytomegalovirus risk, prevention, and management in pediatric solid organ
      transplantation.
AB  - Cytomegalovirus (CMV) is an important cause of morbidity and mortality in
      children who have received organ transplants. Patients have been reported to be
      at differential risk for CMV disease based on the serostatus of the donor and
      recipient with highest risk reported for CMV seronegative recipients who receive
      an organ from a CMV seropositive donor. Prophylaxis with ganciclovir and/or oral
      valganciclovir is reasonable to attempt to prevent CMV infections. A hybrid
      strategy bridging prophylaxis and pre-emptive therapy appears to be emerging as
      an additional method to prevent CMV disease. However, there is no agreement on
      the optimal schedule of testing, duration and dosing of antiviral medications or
      the role of immunoglobulin therapy. This manuscript will review the most recent
      literature and recommendations for the prophylaxis and treatment of CMV
      infections and disease in pediatric transplant recipients. Multicenter,
      randomized, clinical studies involving several pediatric transplant centers are
      needed to determine the best strategies to prevent and treat CMV infections in
      these patients.

PMID- 21199214
TI  - Health-related quality of life in pediatric liver transplant recipients compared
      with other chronic disease groups.
AB  - This cross-sectional, multicenter cohort study compares the level of HRQOL of
      pediatric LT recipients to children with other chronic health conditions. LT
      sample included 873 children who survived at least 12 months following LT. Six
      chronic disease samples were compiled from numerous studies, including over 800
      patients with JRA, type 1 diabetes, cancer in remission, cardiac disease, end
      stage renal disease, and inflammatory bowel disease. Generic HRQOL was measured
      from both the parental and patient perspective using the PedsQLTM 4.0 Generic
      Core Scales. Pediatric LT patients reported better physical health than children
      with JRA. According to parents, pediatric LT recipients had better HRQOL than
      children on renal dialysis on all domains except school functioning. Across all
      domains but emotional functioning, pediatric LT recipients reported significantly
      lower HRQOL than children with type 1 diabetes. Overall, pediatric LT patients
      reported HRQOL comparable to that of children who had undergone renal
      transplantation and patients with cancer in remission. Pediatric LT patients
      manifested impaired HRQOL similar to that of children with chronic diseases and
      these data suggest that they face ongoing challenges that warrant monitoring and
      indicate a need for interventions to improve their HRQOL.

PMID- 21199216
TI  - The utility of comprehensive assessment of donor specific anti-HLA antibodies in
      the clinical management of pediatric kidney transplant recipients.
AB  - Advances in anti-HLA antibody characterization have had a major impact on kidney
      transplantation. Comprehensive characterization of DSA has improved protocols for
      allosensitized transplant candidates, increasing access to acceptable donors.
      Sensitive and specific solid phase antibody detection assays have given important
      insight into the clinical characteristics of antibody-mediated allograft injury,
      resulting in the development of a classification system for acute AMR. In
      addition, important insights into the nature of chronic antibody-mediated
      allograft rejection have been achieved as a result of improvements in DSA
      characterization. Finally, assays initially developed as tools to detect DSA in
      the clinical setting have been employed in innovative research protocols,
      allowing the investigation of new therapeutic approaches.

PMID- 21199219
TI  - Imaging in vivo neuronal transport in genetic model organisms using microfluidic
      devices.
AB  - Microfluidic devices have been developed for imaging behavior and various
      cellular processes in Caenorhabditis elegans, but not subcellular processes
      requiring high spatial resolution. In neurons, essential processes such as
      axonal, dendritic, intraflagellar and other long-distance transport can be
      studied by acquiring fast time-lapse images of green fluorescent protein (GFP)
      tagged moving cargo. We have achieved two important goals in such in vivo studies
      namely, imaging several transport processes in unanesthetized intact animals and
      imaging very early developmental stages. We describe a microfluidic device for
      immobilizing C. elegans and Drosophila larvae that allows imaging without
      anesthetics or dissection. We observed that for certain neuronal cargoes in C.
      elegans, anesthetics have significant and sometimes unexpected effects on the
      flux. Further, imaging the transport of certain cargo in early developmental
      stages was possible only in the microfluidic device. Using our device we observed
      an increase in anterograde synaptic vesicle transport during development
      corresponding with synaptic growth. We also imaged Q neuroblast divisions and
      mitochondrial transport during early developmental stages of C. elegans and
      Drosophila, respectively. Our simple microfluidic device offers a useful means to
      image high-resolution subcellular processes in C. elegans and Drosophila and can
      be readily adapted to other transparent or translucent organisms.

PMID- 21199218
TI  - Regulation of trafficking of activated TrkA is critical for NGF-mediated
      functions.
AB  - Upon activation by nerve growth factor (NGF), TrkA is internalized, trafficked
      and sorted through different endosomal compartments. Proper TrkA trafficking and
      sorting are crucial events as alteration of these processes hinders NGF-mediated
      functions. However, it is not fully known which proteins are involved in the
      trafficking and sorting of TrkA. Here we report that Nedd4-2 regulates the
      trafficking of TrkA and NGF functions in sensory neurons. Depletion of Nedd4-2
      disrupts the correct sorting of activated TrkA at the early and late endosome
      stages, resulting in an accumulation of TrkA in these compartments and, as a
      result of the reduced trafficking to the degradative pathway, TrkA is either
      reverted to the cell surface through the recycling pathway or retrogradely
      transported to the cell body. In addition, Nedd4-2 depletion enhances TrkA
      signaling and the survival of NGF-dependent dorsal root ganglion neurons, but not
      those of brain-derived neurotrophic factor-dependent neurons. Furthermore,
      neurons from a knock-in mouse expressing a TrkA mutant that does not bind Nedd4-2
      protein exhibit increased NGF-mediated signaling and cell survival. Our data
      indicate that TrkA trafficking and sorting are regulated by Nedd4-2 protein.

PMID- 21199220
TI  - Abstracts of the 36th Annual Meeting of the International Society for Pediatric
      and Adolescent Diabetes (ISPAD). October 27-30, 2010. Buenos Aires, Argentina.

PMID- 21199217
TI  - Basolateral sorting signals regulating tissue-specific polarity of heteromeric
      monocarboxylate transporters in epithelia.
AB  - Many solute transporters are heterodimers composed of non-glycosylated catalytic
      and glycosylated accessory subunits. These transporters are specifically
      polarized to the apical or basolateral membranes of epithelia, but this polarity
      may vary to fulfill tissue-specific functions. To date, the mechanisms regulating
      the tissue-specific polarity of heteromeric transporters remain largely unknown.
      Here, we investigated the sorting signals that determine the polarity of three
      members of the proton-coupled monocarboxylate transporter (MCT) family, MCT1,
      MCT3 and MCT4, and their accessory subunit CD147. We show that MCT3 and MCT4
      harbor strong redundant basolateral sorting signals (BLSS) in their C-terminal
      cytoplasmic tails that can direct fusion proteins with the apical marker p75 to
      the basolateral membrane. In contrast, MCT1 lacks a BLSS and its polarity is
      dictated by CD147, which contains a weak BLSS that can direct Tac, but not p75 to
      the basolateral membrane. Knockdown experiments in MDCK cells indicated that
      basolateral sorting of MCTs was clathrin-dependent but clathrin adaptor AP1B
      independent. Our results explain the consistently basolateral localization of
      MCT3 and MCT4 and the variable localization of MCT1 in different epithelia. They
      introduce a new paradigm for the sorting of heterodimeric transporters in which a
      hierarchy of apical and BLSS in the catalytic and/or accessory subunits regulates
      their tissue-specific polarity.

PMID- 21199221
TI  - Sexual health medicine: what is it?

PMID- 21199222
TI  - Cardiovascular risk modification in participants with coronary disease screened
      by the Kidney Early Evaluation Program.
AB  - BACKGROUND: Coronary artery disease (CAD) identifies the need for intensive
      treatment of risk factors among individuals with chronic kidney disease (CKD), a
      high-risk, complex cardiovascular risk state. METHODS: An estimated glomerular
      filtration rate<60 mL/min/1.73 m2 or a urine albumin:creatinine ratio (ACR)>=30
      mg/g (3.4 mg/mmol) defined CKD. RESULTS: Of 70,454 volunteers screened the mean
      age was 53.5+/-15.7 years and 68.3% were female. A total of 5410 (7.7%) had a
      self-reported history of CAD; 1295 (1.8%) had a history of prior percutaneous
      coronary intervention (PCI); and 1124 (1.6%) had a prior history of coronary
      artery bypass surgery (CABG). Multivariate analysis for the outcome of suboptimal
      CAD risk management (composite of systolic blood pressure>=130 mmHg, glucose>=125
      mg/dL (6.9 mmol/L) for diabetics, total cholesterol>=200 mg/dL (5.2 mmol/L), or
      current smoking; n=38,746/53,403, 72.5%) revealed older age (per year) (odds
      ratio (OR)=1.04, 95% confidence interval (CI) 1.03-1.04, P<0.0001), male gender
      (OR=1.40, 95% CI 1.34-1.47, P<0.0001), ACR>=30 mg/g (3.4 mg/mmol) (OR=1.66, 95%
      CI 1.55-1.79, P<0.0001), body mass index (per kg/m2) (OR=1.06, 95% CI 1.06-1.06,
      P<0.0001), CAD without a history of revascularization (OR=1.14, 95% CI 1.02-1.28,
      P=0.02) and care received by a nephrologist (OR=1.49, 95% CI 1.22-1.83, P<0.0001)
      were associated with worse risk factor control. Prior coronary revascularization
      and being under the care of a cardiologist were not associated with either
      improved or suboptimal risk factor control. CONCLUSIONS: Chronic kidney disease
      is associated with overall poor rates of CAD risk factor control.

PMID- 21199223
TI  - The epidemiology and characteristics of type 2 diabetes in urban, community-based
      young people.
AB  - As little is known about the impact of type 2 diabetes amongst Australian youth
      despite international increases in childhood obesity, we aimed to identify and
      characterize people aged<25 years with type 2 diabetes in an urban community with
      60,000 people aged 10-24 years. The estimated maximum prevalence (59/100,000
      persons) was lower than US estimates but higher than in Asia and Europe. In eight
      patients assessed in detail, obesity and related comorbidities were common, and
      quality of life was low.

PMID- 21199224
TI  - Fixed dose (555 MBq; 15 mCi) radioiodine for the treatment of hyperthyroidism:
      outcome and its predictors.
AB  - Radioiodine therapy (RIT) is an accepted treatment for hyperthyroidism and a 555
      MBq (15-mCi) dose is frequently used. We aimed to assess treatment outcome with
      this dose, and to identify predictors of successful treatment. An analysis of 478
      treated patients demonstrated an overall four-month cure rate of 79.5%; success
      rate was higher in patients with toxic multinodular goitre, solitary toxic
      adenoma, a smaller thyroid or less severe disease. This information may be of
      further assistance if variation in the dose of RIT is considered.

PMID- 21199225
TI  - Gastrointestinal Kaposi's sarcoma: a rare cause of vomiting with a dramatic
      response to treatment.

PMID- 21199226
TI  - Factor V Leiden mutation with retinal vascular occlusion.

PMID- 21199227
TI  - Pneumocytoma: an unusual epithelioid lung neoplasm.

PMID- 21199228
TI  - Fibrodysplasia ossificans progressiva presenting as ankylosing spondylitis.

PMID- 21199229
TI  - Chemotherapy for hormone-refractory prostate cancer: a physician's dilemma.

PMID- 21199230
TI  - The future of clinical genetics.

PMID- 21199231
TI  - Can faecal lactoferrin be used as a discriminator for referral for colonoscopy?

PMID- 21199232
TI  - Radiology images.

PMID- 21199234
TI  - Effects of toe and ankle training in older people: a cross-over study.
AB  - AIM: Maintenance of physical function in the elderly is important. Previous
      studies have focused mainly on training-center-based interventions, accompanied
      by training staff or equipped with training machinery. The purpose of this study
      was to investigate the effects of toe and ankle training for the elderly.
      METHODS: The four facilities were divided into two groups that received the
      intervention in 8-week shifts. An exercise program, focused mainly on ankle, foot
      and toe function, was conducted with the subject in a sitting position. Muscle
      strength, physical function, fear of falling and health-related quality of life
      were assessed at the beginning of the study and at the end of each 8-week phase.
      Because subjects were not randomized, significant intergroup differences were
      present in some baseline measurements. Therefore, the study was conducted with a
      cross-over design, and ancova was included with the baseline value as an
      independent covariate. RESULTS: A significant improvement was found in quadriceps
      strength, functional reach, stepping in sitting and Euro Qol EQ5D score, together
      with a possible improvement in toe flexor strength. CONCLUSION: These results
      suggest that a training program carried out with the subject in a sitting
      position and focused mainly on ankle, foot and toe functions is effective in
      improving some aspects of motor function in the elderly. This approach may help
      elderly individuals maintain their activity level without increasing risks.

PMID- 21199233
TI  - Association of lower hemoglobin level with depressive mood in elderly women at
      high risk of requiring care.
AB  - AIM: Despite the high prevalence of anemia and depression in the elderly, there
      have been few studies exploring the association between these two conditions. In
      the current study, we analyzed the association of hemoglobin level and depressive
      mood in a group of community-dwelling elderly at high risk of requiring care.
      METHODS: All participants at a health check in a group of community-dwelling
      elderly (1163 men and 2651 women) filled out a basic yes/no questionnaire
      consisting of simple assessments of their instrumental activities of daily living
      (7 items), memory problems (3 items), walking status (5 items), dysphagia (3
      items), nutritional status (2 items) and depressive mood (5 items). Other
      examinations, including blood testing, were also performed. Multiple regression
      analysis with the score of depressive mood in the basic checklist was performed.
      The hemoglobin level was set for an explanatory value after adjustment for age,
      blood pressure, electrocardiogram abnormality, instrumental activities of daily
      living, walking status, nutritional status, dysphagia and memory problems.
      RESULTS: It was found that 30.5% of women and 31.8% of men had anemia. When the
      subjects were divided with depressive score of 2 points or more (the highest
      possible score was 5) and less, those with a higher depressive score had
      significantly lower hemoglobin levels than those with a lower score. Multiple
      regression analysis showed that lower hemoglobin level was significantly
      associated with depressive mood only in women (P=0.046) but not in men (P=0.579).
      CONCLUSION: Lower hemoglobin level was significantly associated with depressive
      mood in elderly women at high risk for care, but not in elderly men at high risk
      for care.

PMID- 21199236
TI  - Cardiovascular protection afforded by caloric restriction: essential role of
      nitric oxide synthase.
AB  - Caloric restriction is an established intervention, of which anti-aging effects
      are scientifically proven. It has pleiotropic effects on the cardiovascular
      system: vascular protection, improvement of myocardial ischemic tolerance and
      retardation of cardiac senescence. First, increasing evidence from both
      experimental and clinical studies supports the concept that "a man is as old as
      his arteries". Caloric restriction could prevent the progression of
      atherosclerosis and vascular aging through direct and indirect mechanisms.
      Second, the hearts of senescent animals are more susceptible to ischemia than
      those of young animals. We demonstrated that short-term and prolonged caloric
      restriction confers cardioprotection against ischemia/reperfusion injury in young
      and aged rodents. Furthermore, we showed that the increase in circulating
      adiponectin levels and subsequent activation of adenosine monophosphate-activated
      protein kinase are necessary for the cardioprotection afforded by short-term
      caloric restriction. In contrast, the mechanisms by which prolonged caloric
      restriction confers cardioprotection seem more complicated. Adiponectin, nitric
      oxide synthase and sirtuin may form a network of cardiovascular protection during
      caloric restriction. Recently, by using genetically engineered mice, we found
      that, in addition to endothelial nitric oxide synthase, neuronal nitric oxide
      synthase plays an essential role in the development of cardioprotection afforded
      by prolonged caloric restriction. Third, long-term caloric restriction has
      cardiac-specific effects that attenuate the age-associated impairment seen in
      left ventricular diastolic function. It is possible that long-term caloric
      restriction partially retards cardiac senescence by attenuating oxidative damage
      in the aged heart. Overall, we strongly believe that caloric restriction could
      reduce morbidity and mortality of cardiovascular events in humans.

PMID- 21199235
TI  - Galantamine (Reminyl) once daily outcome and satisfaction survey (RODOS) in mild
      to moderate Alzheimer's disease: a study in a real life population.
AB  - AIM: To record in real life the appreciation of elderly patients, their
      caregivers and physicians of a once daily formulation of prolonged release of
      galantamine in the treatment of mild to moderate Alzheimer's disease. METHODS: A
      prospective, multicenter, observational study was conducted in 128 elderly
      patients, treated for 6 months with galantamine, donepezil or rivastigmine.
      RESULTS: Of the patients treated with galantamine, 82 of the 97 (84.5%) were
      continuing their treatment after 6 months. These patients reported their
      condition as improved in 49%, unchanged in 47% and worsened in 4%. Caregivers
      rated global evaluation as 37% better, 41% unchanged and 22% worse. Physicians
      rated global clinical impression of change as 46% better, 34% unchanged and 20%
      worse. Measurements of cognition and behavior remained stable. The appreciation
      of physicians and caregivers corresponded well (P<0.001). The incidence of
      serious side-effects possibly related to galantamine was 9.3%, which was not
      different from that in patients treated with other cholinesterase inhibitors.
      CONCLUSION: In a real life setting, galantamine once daily is safe and is
      favorably appreciated by patients, their caregivers and physicians.

PMID- 21199238
TI  - Mental health nursing: What it is or what it does?

PMID- 21199237
TI  - Elcatonin is effective for lower back pain and the symptoms of gastroesophageal
      reflux disease in elderly osteoporotic patients with kyphosis.
AB  - AIM: Elderly osteoporotic patients with kyphosis tend to be frequently
      accompanied by the symptoms of gastroesophageal reflux disease (GERD) such as
      heartburn and acid reflux. Elcatonin, which is effective for lower back pain of
      osteoporosis, has a physiological action of reducing gastric acid. We examine
      whether or not this drug would alleviate GERD symptoms as well as lower back pain
      in patients with osteoporosis. METHODS: Elcatonin was administrated at a dose of
      20 units once weekly for 3 months. The visual analog scale (VAS) and the
      frequency scale for the symptoms of GERD (FSSG) were used to evaluate lower back
      pain and GERD symptoms, respectively. RESULTS: Both VAS and FSSG scores
      significantly decreased after 1, 2 and 3 months of elcatonin administration (at
      least P < 0.001). Even after the cessation of elcatonin, both scores remained
      significantly low for an extra 1 and 3 months, respectively. These beneficial
      effects were also observed in non-steroidal anti-inflammatory drug (NSAID) or
      GERD drug users. CONCLUSION: The present findings suggest that elcatonin could
      improve the symptoms of GERD as well as osteoporosis-invoked back pain in elderly
      patients with kyphosis, and that these effects are long-lasting and independent
      of NSAID or GERD drugs.

PMID- 21199239
TI  - Listening to mental health workers' experiences: factors influencing their work
      with women who disclose sexual assault.
AB  - Women are overrepresented within mental health service-use statistics, and a
      disproportionate number of them have experienced sexual assault. While mental
      health workers are often the first point of contact between these women and the
      mental health system, within the research to date, women have often reported a
      negative experience of disclosing sexual assault to these workers. This article
      presents findings from an exploratory Australian study. The aim of the study was
      to explore factors that influenced how mental health Crisis Assessment and
      Treatment Service (CATS) workers respond to women who disclose sexual assault in
      crisis service settings. Fifteen CATS workers were surveyed and the predominantly
      qualitative data were then analysed using thematic analysis. This article
      presents two key findings: (i) the majority of participants had not experienced
      adequate sexual assault training, and seven of the 15 did not feel well equipped
      to respond to a disclosure of sexual assault; and (ii) they rarely consulted or
      referred women to specialist sexual assault services, despite recognizing the
      significant impact of sexual assault on mental health functioning.
      Recommendations are made for training and increased communication between mental
      health and sexual assault service systems to ensure better outcomes for women.

PMID- 21199240
TI  - Reducing sexually-transmitted infection risk in young people with first-episode
      psychosis.
AB  - There is emerging evidence that young people with first-episode psychosis are at
      greater risk of sexually-transmitted infections (STI) than their peers.
      Theoretical constructs central to behavioural change theories, broadly defined as
      sexual health-related knowledge, attitudes, and beliefs, have guided most sexual
      risk-reduction interventions in other at-risk populations. The role of these
      constructs in the sexual risk behaviour of young people with early psychosis
      remains unknown. A convenience sample of 67 young people with first-episode
      psychosis and 48 healthy controls matched on a number of sociodemographic
      characteristics was recruited. Participants completed a survey assessing their
      sexual behaviour and sexual health-related knowledge, attitudes, and beliefs.
      Group differences and the role of these constructs in the condom-use behaviour of
      these young people were examined. Although some differences emerged, group
      similarities were prominent. Inconsistent condom use was predicted by clinical
      status, unemployment, and the absence of peer support for condom use. These
      results support previous findings that young people with psychosis have greater
      needs for STI prevention due to increased rates of unprotected sex. Risk
      reduction interventions that target peer influence are important. Inquiry into a
      broader range of psychosocial factors could further our understanding of STI
      infection risk in early psychosis.

PMID- 21199241
TI  - Talking or avoiding? Mental health nurses' views about discussing sexual health
      with consumers.
AB  - Mental health consumers are sexual beings; however, their sexual desire,
      capacity, and ability to maintain previous sexual patterns can be altered by
      their illness or by the effects and side-effects of medications. The sexuality of
      consumers has been poorly addressed, and the limited evidence suggests that
      mental health nurses remain ambivalent to including sexuality in their care. This
      paper presents the findings of a research project investigating the practices of
      mental health nurses in assessing and supporting the sexuality of consumers. A
      qualitative, exploratory approach underpinned individual interviews with 14
      mental health nurses from inpatient and community settings. The participants
      acknowledged the importance of sexuality; however, most were reluctant to enquire
      about consumer concerns and tended to either ignore the issue or refer it to
      another clinician. Four themes were identified: talking about or avoiding
      sexuality concerns with consumers; sexuality is not an important priority; refer
      to others, as talking about sexuality is not 'my' job; and sexuality is poorly
      addressed by others. It is important that barriers to the assessment and
      discussion of sexuality are identified, and measures are taken to overcome them.

PMID- 21199242
TI  - Experience of living with a family member with bipolar disorder.
AB  - Bipolar disorder (BD) is a severe illness that has a serious impact on the lives
      of those affected and on their families. The aim of this study was to elucidate
      what it means for family members to live with an adult person who has BD, with
      reference to their views concerning the condition of the person affected and the
      future. During 2005, 17 family members of people with the disorder were
      interviewed, and the data obtained were subjected to a qualitative content
      analysis. The findings showed that family members felt alone with their
      experiences and struggled to make sense of and to maintain normality, as their
      life was encroached on by the condition. Bearing the burden of responsibility and
      control made it difficult for family members to focus on their own future. To
      build hope, they needed opportunities to share their experiences with others,
      increased understanding of the condition, and relief from the burden they bore.
      This study underlines the importance of strengthening support holistically for
      family members living with an adult person with BD. Support and interventions
      concerning these families' needs have to be developed and should be provided by
      all mental health-care services.

PMID- 21199243
TI  - Creating a new whole: helping families of people with schizophrenia.
AB  - Collaboration between psychiatric nurses and family members is considered an
      important part of caring for people with schizophrenia either in hospital or at
      home after discharge. Studies have demonstrated family involvement in terms of
      caring for patients who have been discharged early from hospital. An extensive
      review of the literature and related studies regarding nursing interventions have
      been done, but there have been limited studies on what psychiatric nurses
      actually do when working with the families of people with schizophrenia in
      Thailand. The purpose of the present study was to explore relationships between
      Thai psychiatric nurses and families in terms of administering nursing care to
      patients. Grounded theory methodology was used to examine the processes through
      which psychiatric nurses work with families. Data were collected by 16
      psychiatric nurses through in-depth interviews, observations, and field notes.
      Data were analyzed using constant and comparative methods of other studies, which
      revealed the process by which nurses can create a new whole between families,
      patients, and Thai psychiatric nurses. The process consists of four major stages:
      establishing trust, strengthening connections, promoting readiness to care, and
      supporting family.

PMID- 21199244
TI  - Collaboration between mental health consumers and nurses: shared understandings,
      dissimilar experiences.
AB  - Adopting a collaborative approach within clinical relationships is illustrative
      of consumers' and nurses' positive beliefs, values, and attitudes towards each
      other and their partnership. However, for collaboration to be successful, how
      roles are determined, how each partner relates to the other, and how decisions
      are to be made need to be clearly defined and agreed upon. The research study
      described here utilized a mixed-method approach comprising focus groups and
      surveys to explore the subjective understandings, attitudes, and experiences of
      consumer-nurse collaboration within a mental health rehabilitation context in
      order to more clearly determine the conditions for successful nurse-consumer
      collaboration. The study found that although consumers and nurses conceptualized
      collaboration in similar ways, their lived experiences were disparate. A key
      finding of the study was that mutual recognition of each others' knowledge and
      expertise is needed for successful collaboration. The study reinforced the need
      for consumers and nurses to establish common ground on which to collaborate and
      to articulate the behaviours and expectations of working collaboratively. While
      collaboration was acknowledged as a significant and desirable basis for
      therapeutic relationships, it was challenged by determinants of power, such as
      knowledge, information, and expertise.

PMID- 21199245
TI  - 'I wanted to learn how to heal my heart': family carer experiences of receiving
      an emotional support service in the Well Ways programme.
AB  - Family carers of people with mental illness provide an immense contribution to
      society in caring for mental health consumers. However, carers can experience
      substantial burdens and poor health outcomes themselves. Recognition of their
      needs for education and support has led to the development of a range of family
      education programmes. Throughout Australia, the Mental Illness Fellowship
      Australia offers the Well Ways programme, a group-based, family-to-family,
      education programme that provides information and aims to increase carers'
      capacity to care effectively for themselves, their families, and the mental
      health consumers. This paper describes a qualitative evaluation of an emotional
      support service piloted in a Well Ways programme in rural Queensland, Australia.
      The pilot service comprised individual emotional support offered to family carers
      attending the weekly Well Ways group education programme. Six of eight family
      carers who received the emotional support engaged in semistructured interviews
      exploring their experience of receiving the support. Three themes emerged from
      their experience: dealing with difficult times, connecting through shared
      experience, and exploring different options. Family carers found the emotional
      support beneficial, and reported that it enhanced their capacity to manage their
      own well-being, as well as their caregiving roles.

PMID- 21199246
TI  - Family group conferences in public mental health care: an exploration of
      opportunities.
AB  - Family group conferences are usually organized in youth care settings, especially
      in cases of (sexual) abuse of children and domestic violence. Studies on the
      application of family group conferences in mental health practices are scarce,
      let alone in a setting even more specific, such as public mental health care. The
      present study reports on an exploratory study on the applicability of family
      group conferencing in public mental health care. Findings suggest that there are
      six reasons to start family group conference pilots in public mental health care.
      First, care providers who work in public mental health care often need to deal
      with clients who are not motivated in seeking help. Family group conferences
      could yield support or provide a plan, even without the presence of the client.
      Second, conferences might complement the repertoire of treatment options between
      voluntary help and coercive treatment. Third, clients in public mental health
      care often have a limited network. Conferences promote involvement, as they
      expand and restore relationships, and generate support. Fourth, conferences could
      succeed both in a crisis and in other non-critical situations. Sometimes pressure
      is needed for clients to accept help from their network (such as in the case of
      an imminent eviction), while in other situations, it is required that clients are
      stabilized before a conference can be organized (such as in the case of a
      psychotic episode). Fifth, clients who have negative experiences with care
      agencies and their representatives might be inclined to accept a conference
      because these agencies act in another (modest) role. Finally, the social network
      could elevate the work of professionals.

PMID- 21199247
TI  - Biomass transformation webs provide a unified approach to consumer-resource
      modelling.
AB  - An approach to modelling food web biomass flows among live and dead compartments
      within and among species is formulated using metaphysiological principles that
      characterise population growth in terms of basal metabolism, feeding, senescence
      and exploitation. This leads to a unified approach to modelling interactions
      among plants, herbivores, carnivores, scavengers, parasites and their resources.
      Also, dichotomising sessile miners from mobile gatherers of resources, with
      relevance to feeding and starvation time scales, suggests a new classification
      scheme involving 10 primary categories of consumer types. These types, in various
      combinations, rigorously distinguish scavenger from parasite, herbivory from
      phytophagy and detritivore from decomposer. Application of the approach to
      particular consumer-resource interactions is demonstrated, culminating in the
      construction of an anthrax-centred food web model, with parameters applicable to
      Etosha National Park, Namibia, where deaths of elephants and zebra from the
      bacterial pathogen, Bacillus anthracis, provide significant subsidies to jackals,
      vultures and other scavengers.

PMID- 21199248
TI  - Stepping in Elton's footprints: a general scaling model for body masses and
      trophic levels across ecosystems.
AB  - Despite growing awareness of the significance of body-size and predator-prey body
      mass ratios for the stability of ecological networks, our understanding of their
      distribution within ecosystems is incomplete. Here, we study the relationships
      between predator and prey size, body-mass ratios and predator trophic levels
      using body-mass estimates of 1313 predators (invertebrates, ectotherm and
      endotherm vertebrates) from 35 food-webs (marine, stream, lake and terrestrial).
      Across all ecosystem and predator types, except for streams (which appear to have
      a different size structure in their predator-prey interactions), we find that (1)
      geometric mean prey mass increases with predator mass with a power-law exponent
      greater than unity and (2) predator size increases with trophic level. Consistent
      with our theoretical derivations, we show that the quantitative nature of these
      relationships implies systematic decreases in predator-prey body-mass ratios with
      the trophic level of the predator. Thus, predators are, on an average, more
      similar in size to their prey at the top of food-webs than that closer to the
      base. These findings contradict the traditional Eltonian paradigm and have
      implications for our understanding of body-mass constraints on food-web topology,
      community dynamics and stability.

PMID- 21199249
TI  - Comparing the qualitatively different effects rapidly evolving and rapidly
      induced defences have on predator-prey interactions.
AB  - Interspecific interactions depend not only on the population densities of the
      interacting species, but on their phenotypes as well. Phenotypic variation can be
      plastic or heritable and both mechanisms can drive phenotypic change at rates
      comparable to or faster than those of ecological dynamics (e.g. changes in
      population abundances or spatial distributions). In this study, we compare the
      effects rapidly induced and rapidly evolving defences have on community dynamics
      by considering the fast phenotypic change limit using fast-slow systems theory.
      Our approach allows us to study phenotypically plastic and evolving systems with
      one overarching theory, thus capturing the effects rapidly induced defences have
      on ecological dynamics and how those effects differ from the effects of evolving
      defences. Our results show that rapidly induced defences tend to stabilize
      community dynamics and that some behaviours observed in rapidly evolving systems
      cannot be produced by phenotypic plasticity.

PMID- 21199250
TI  - Polymorphism and recombination for rDNA in the putatively asexual microsporidian
      Nosema ceranae, a pathogen of honeybees.
AB  - Nosema ceranae is currently one of the major pathogens of honeybees, related to
      the worldwide colony losses phenomenon. The genotyping of strains based on
      ribosomal DNA (rDNA) can be misleading if the repeated units are not identical.
      The analysis of cloned rDNA fragments containing the intergenic spacer (IGS) and
      part of the rDNA small-subunit (SSU) gene, from N. ceranae isolates from
      different European and Central Asia populations, revealed a high diversity of
      sequences. The variability involved single-nucleotide polymorphisms and
      insertion/deletions, resulting in 79 different haplotypes. Two sequences from the
      same isolate could be as different as any pair of sequences from different
      samples; in contrast, identical haplotypes were also found in very different
      geographical origins. Consequently, haplotypes cannot be organized in a
      consistent phylogenetic tree, clearly indicating that rDNA is not a reliable
      marker for the differentiation of N. ceranae strains. The results indicate that
      recombination between different sequences may produce new variants, which is
      quite surprising in microsporidia, usually considered to have an asexual mode of
      reproduction. The diversity of sequences and their geographical distribution
      indicate that haplotypes of different lineages may occasionally be present in a
      same cell and undergo homologue recombination, therefore suggesting a sexual
      haplo-diploid cycle.

PMID- 21199251
TI  - Selective lignin and polysaccharide removal in natural fungal decay of wood as
      evidenced by in situ structural analyses.
AB  - Selective modification/degradation of the main plant polymers (cellulose,
      hemicelluloses and lignin) was investigated in a hardwood after white and brown
      rot fungal decay under environmental conditions. The chemical changes produced in
      the plant cell wall were analysed in situ, by nuclear magnetic resonance (NMR) at
      the gel state, and analytical pyrolysis. Two-dimensional (2D) NMR of the white
      rotted wood showed only cellulose and (deacetylated) hemicellulose, and the
      complete removal of lignin. On the other hand, the brown-rotted wood showed the
      nearly complete absence of polysaccharides, while the main features of lignin
      structure, as revealed by 2D-NMR, could be observed. These included well-resolved
      aromatic and side-chain cross-signals, although the intensity of the latter
      signals was lowered indicating a reduction in the number of side-chain linkages
      (beta-O-4' and beta-beta') per aromatic unit (their relative abundances remaining
      unchanged). These results contrast with a recent study concluding that the
      aromatic polymer after brown-rot decay is not longer recognized as lignin. Some
      oxidative alteration of lignin during brown-rot decay was evidenced and, more
      interesting, several compounds with 3-methoxycatechol skeleton were released upon
      pyrolysis. Lignin demethylation is consistent with recent brown-rot
      transcriptomic/secretomic studies showing overexpression of methanol oxidase,
      which could use lignin-derived methanol to generate the peroxide required for
      cellulose depolymerization via Fenton chemistry.

PMID- 21199252
TI  - The octahaem SirA catalyses dissimilatory sulfite reduction in Shewanella
      oneidensis MR-1.
AB  - Shewanella oneidensis MR-1 is a metal reducer that uses a large number of
      electron acceptors including thiosulfate, polysulfide and sulfite. The enzyme
      required for thiosulfate and polysulfide respiration has been recently
      identified, but the mechanisms of sulfite reduction remained unexplored. Analysis
      of MR-1 cultures grown anaerobically with sulfite suggested that the
      dissimilatory sulfite reductase catalyses six-electron reduction of sulfite to
      sulfide. Reduction of sulfite required menaquinones but was independent of the
      intermediate electron carrier CymA. Furthermore, the terminal sulfite reductase,
      SirA, was identified as an octahaem c cytochrome with an atypical haem binding
      site. The sulfite reductase of S. oneidensis MR-1 does not appear to be a
      sirohaem enzyme, but represents a new class of sulfite reductases. The gene that
      encodes SirA is located within a 10-gene locus that is predicted to encode a
      component of a specialized haem lyase, a menaquinone oxidase and copper transport
      proteins. This locus was identified in the genomes of several Shewanella species
      and appears to be linked to the ability of these organisms to reduce sulfite
      under anaerobic conditions.

PMID- 21199254
TI  - Red but not dead? Membranes of stressed Saccharomyces cerevisiae are permeable to
      propidium iodide.
AB  - Flow cytometric monitoring of propidium iodide (PI) uptake is a well-established
      and rapid method for monitoring cell death and is used on the basis that the
      intact membrane of viable cells excludes the propidium ion and that loss of this
      permeability barrier represents irreparable damage and thus cell death. These
      assumptions are typically based on analysis of live and killed cells. Here we
      have identified stress levels that lead to a loss of viability of a proportion of
      Saccharomyces cerevisiae cells and under these conditions we show that there is a
      subpopulation of cells that can take up PI during and immediately following
      exposure to stress but that a short incubation allows repair of the membrane
      damage such that subsequent exposure to PI does not result in staining.
      Irrespective of the stress applied, approximately 7% of cells exhibited the
      ability to repair. These results indicate that the level of damage that the yeast
      cell membrane can sustain and yet retain the ability to repair is greater than
      previously recognized and care must therefore be taken in using the terms 'PI
      positive' and 'dead' synonymously. We discuss these findings in the context of
      the potential for such environmental stress-induced, transient membrane
      permeability to have evolutionary implications via the facilitation of horizontal
      gene transfer.

PMID- 21199253
TI  - Global patterns in the biogeography of bacterial taxa.
AB  - Bacteria control major nutrient cycles and directly influence plant, animal and
      human health. However, we know relatively little about the forces shaping their
      large-scale ecological ranges. Here, we reveal patterns in the distribution of
      individual bacterial taxa at multiple levels of phylogenetic resolution within
      and between Earth's major habitat types. Our analyses suggest that while macro
      scale habitats structure bacterial distribution to some degree, abundant bacteria
      (i.e. detectable using 16S rRNA gene sequencing methods) are confined to single
      assemblages. Additionally, we show that the most cosmopolitan taxa are also the
      most abundant in individual assemblages. These results add to the growing body of
      data that support that the diversity of the overall bacterial metagenome is
      tremendous. The mechanisms governing microbial distribution remain poorly
      understood, but our analyses provide a framework with which to test the
      importance of macro-ecological environmental gradients, relative abundance,
      neutral processes and the ecological strategies of individual taxa in structuring
      microbial communities.

PMID- 21199255
TI  - Marine subsurface eukaryotes: the fungal majority.
AB  - Studies on the microbial communities of deep subsurface sediments have indicated
      the presence of Bacteria and Archaea throughout the sediment column. Microbial
      eukaryotes could also be present in deep-sea subsurface sediments; either
      bacterivorous protists or eukaryotes capable of assimilating buried organic
      carbon. DNA- and RNA-based clone library analyses are used here to examine the
      microbial eukaryotic diversity and identify the potentially active members in
      deep-sea sediment cores of the Peru Margin and the Peru Trench. We compared
      surface communities with those much deeper in the same cores, and compared cores
      from different sites. Fungal sequences were most often recovered from both DNA-
      and RNA-based clone libraries, with variable overall abundances of different
      sequence types and different dominant clone types in the RNA-based and the DNA
      based libraries. Surficial sediment communities were different from each other
      and from the deep subsurface samples. Some fungal sequences represented
      potentially novel organisms as well as ones with a cosmopolitan distribution in
      terrestrial, fresh and salt water environments. Our results indicate that fungi
      are the most consistently detected eukaryotes in the marine sedimentary
      subsurface; further, some species may be specifically adapted to the deep
      subsurface and may play important roles in the utilization and recycling of
      nutrients.

PMID- 21199257
TI  - Inducible NO synthase and antibacterial host defence in times of Th17/Th22/T22
      immunity.
AB  - During the last two decades nitric oxide (NO) produced by inducible NO synthase
      (iNOS or NOS2) has been characterized as immunoregulatory and antimicrobial
      principle displaying the potential to determine course of disease in a range of
      infections. Being an enzyme primarily regulated on expressional level, cytokine
      driven iNOS appears to be connected in particular with activation of Th1-type
      immunity. However, with the recent advent of additional, partly overlapping
      CD4(+) T cell effector subsets, namely Th17 and Th22 cells, a further layer of
      complexity has been added to immunoregulatory networks determining inflammatory
      gene expression in the context of microbial infections. Here, we review current
      knowledge on activation of iNOS function by interleukin (IL)-17 and IL-22 with
      focus on Th17/Th22-directed antibacterial immunity.

PMID- 21199258
TI  - Cellular interactions by LPxTG-anchored pneumococcal adhesins and their
      streptococcal homologues.
AB  - In this review we focus on three important families of LPxTG-anchored adhesins in
      the human pathogen Streptococcus pneumoniae, but also their homologues in related
      streptococci. We discuss the contribution of these streptococcal adhesins to host
      tropism, pathogenesis and their interactions with different host cell types. The
      first surface structures discussed are the heteropolymeric pili that have been
      found in important streptococcal pathogens such as S. pneumoniae, S. pyogenes, S.
      agalactiae and E. faecalis/faecium. Major and minor pilus subunit proteins are
      covalently joined and finally attached to the cell wall through the action of
      specific sortases. The role of pili and individual pilin subunits in adhesion and
      pathogenesis and their structure and assembly in different streptococcal species
      are being covered. Furthermore, we address recent findings regarding a family of
      large glycosylated serine-rich repeat (SRR) proteins that act as fibrillar
      adhesins for which homologues have been found in several streptococcal species
      including pneumococci. In the pneumococcal genome both pili and its giant SRR
      protein are encoded by accessory genes present in particular clonal lineages for
      which epidemiological information is available. Finally, we briefly discuss the
      role played by the pneumococcal neuraminidase NanA in adhesion and pathogenesis.

PMID- 21199259
TI  - Cyclic AMP signalling in mycobacteria: redirecting the conversation with a common
      currency.
AB  - cAMP is an ancient second messenger, and is used by many organisms to regulate a
      wide range of cellular functions. Mycobacterium tuberculosis complex bacteria are
      exceptional in that they have genes for at least 15 biochemically distinct
      adenylyl cyclases, the enzymes that generate cAMP. cAMP-associated gene
      regulation within tubercle bacilli is required for their virulence, and secretion
      of cAMP produced by M. tuberculosis bacteria into host macrophages disrupts the
      host's immune response to infection. In this review, we discuss recent advances
      in our understanding of the means by which cAMP levels are controlled within
      mycobacteria, the importance of cAMP to M. tuberculosis during host infection,
      and the role of cAMP in mycobacterial gene regulation. Understanding the myriad
      aspects of cAMP signalling in tubercle bacilli will establish new paradigms for
      cAMP signalling, and may contribute to new approaches for prevention and/or
      treatment of tuberculosis disease.

PMID- 21199261
TI  - Abstracts of the 1st International Diabetes and Obesity Forum (IDOF). October 21
      23, 2010. Athens, Greece.

PMID- 21199260
TI  - Dual roles of NOD2 in TLR4-mediated signal transduction and -induced inflammatory
      gene expression in macrophages.
AB  - NOD2 of the NLRs and TLR4 of the TLRs are major pattern-recognition receptors,
      which sense different microbial pathogens and have important roles in innate
      immunity. Herein, we investigated the roles of NOD2 in TLR4-mediated signalling
      and gene regulation in RAW264.7 macrophages. We found that MDP (a NOD2 ligand)
      increased LPS-induced expressions of TNF-alpha, IL-1beta, IL-6, iNOS and COX-2.
      MDP did not affect LPS-induced activation of MAPKs or IKK, while it potentiated
      LPS-induced NF-kappaB activation. Meanwhile TLR4 activation increased NOD2 mRNA
      expression, and upregulated NOD2 upon MDP treatment is a positive regulator of
      TLR4-mediated signalling. Intriguingly we found that NOD2 silencing led to
      increases in LPS-induced signal transduction and inflammatory responses, and a
      decrease in LPS-elicited homologous tolerance. We thus propose that NOD2 in the
      absence of MDP treatment might also play a negative regulatory role in the action
      of TLR4. Further, we demonstrated that both CARD and LRR domains of the NOD2
      protein were responsible for the negative regulatory action on TLR4. In summary,
      it is the first time to demonstrate that NOD2 have dual effects on TLR4
      signalling and exert a novel ligand-independent action. Elucidating molecular
      mechanisms by which NOD2 exerts its ligand-independent action on TLR4 requires
      further investigation.

PMID- 21199262
TI  - Pharmacological management of type 2 diabetes: the potential of incretin-based
      therapies.
AB  - Management guidelines recommend metformin as the first-line therapy for most
      patients with type 2 diabetes uncontrolled by diet and exercise. Efficacy with
      metformin therapy is usually of limited duration, which necessitates the early
      introduction of one or two additional oral agents or the initiation of
      injections, glucagon-like peptide-1 (GLP-1) agonists or insulin. Although safe
      and effective, metformin monotherapy has been associated with gastrointestinal
      side effects (~20% of treated patients in randomized studies) and is
      contraindicated in patients with renal insufficiency or severe liver disease.
      Patients treated with a sulphonylurea are at increased risk for hypoglycaemia and
      moderate weight gain, whereas those receiving a thiazolidinedione are subject to
      an increased risk of weight gain, oedema, heart failure or fracture. Weight gain
      and hypoglycaemia are associated with insulin use. Thus, there is an unmet need
      for a safe and efficacious add-on agent after initial-therapy failure. Evidence
      suggests that incretin-based agents, such as GLP-1 receptor agonists and
      dipeptidyl peptidase-4 inhibitors, can successfully achieve glycaemic targets and
      potentially provide cardiovascular and beta-cell-function benefits. This review
      will examine current approaches for treating type 2 diabetes and discuss the
      place of incretin therapies, mainly GLP-1 agonists, in the type 2 diabetes
      treatment spectrum.

PMID- 21199263
TI  - The potential role of glucagon-like peptide-1 or its analogues in enhancing
      glycaemic control in critically ill adult patients.
AB  - Intravenous insulin therapy is the gold standard therapy for glycaemic control in
      hyperglycaemic critically ill adult patients. However, hypoglycaemia remains a
      major concern in critically ill patients, even in some populations who are not
      receiving infused insulin. Furthermore, the influence of factors such as
      glycaemic variability and nutritional support may conceal any benefit of strict
      glycaemic control on morbidity and mortality in these patients. The recently
      revised guidelines of the American Diabetic Association/American College of
      Clinical Endocrinologists no longer advocate very tight glycaemic control or
      normalization of glucose levels in all critically ill patients. In the light of
      various concerns over the optimal glucose level and means to achieve such
      control, the use of glucagon-like peptide-1 or its analogues administered
      intravenously may represent an interesting therapeutic option.

PMID- 21199264
TI  - Fuelling the athlete with type 1 diabetes.
AB  - People with type 1 diabetes (T1DM) want to enjoy the benefits of sport and
      exercise, but management of diabetes in this context is complex. An understanding
      of the physiology of exercise in health, and particularly the control of fuel
      mobilization and metabolism, gives an idea of problems which may arise in
      managing diabetes for sport and exercise. Athletes with diabetes need to be
      advised on appropriate diet to maximize performance and reduce fatigue. Exercise
      in diabetes is complicated both by hypoglycaemia and hyperglycaemia in particular
      circumstances and explanations are advanced which can provide a theoretical
      underpinning for possible management strategies. Management strategies are
      proposed to improve glycaemic control and performance.

PMID- 21199266
TI  - Patient perspectives on once-weekly medications for diabetes.
AB  - AIM: to examine patient beliefs, preferences and concerns regarding a once-weekly
      (QW) glucose-lowering medication option. METHODS: a total of 1516 adults with
      type 2 diabetes drawn from a national Chronic Illness Panel completed an
      anonymous online survey that assessed perceived attributes of QW therapy,
      willingness to take an injectable QW medication and patient characteristics that
      might influence their willingness, such as current perceived glycaemic control
      and diabetes quality of life (DQOL). RESULTS: positive attitudes regarding QW
      medication were common, with current injection users significantly more likely
      than non-injection users to view beneficial aspects: greater convenience, better
      medication adherence, improved quality of life (QOL) and a less overwhelming
      sense of treatment (in all cases, p < 0.001). In all, 46.8% reported that they
      would likely take an injectable QW medication if recommended by their physician,
      with current injection users more than twice as likely as non-injection users
      (73.1 vs. 31.5%; p < 0.001). Greater willingness to take QW medications was
      associated with poorer DQOL [injection users only; odds ratio (OR) = 1.37, p <
      0.01] and poorer perceived glycaemic control (non-injection users only; OR =
      1.24, p < 0.05). Concerns arose about consistency of dosage over time, potential
      forgetfulness and cost. CONCLUSIONS: QW glucose-lowering medications are viewed
      positively by patients with type 2 diabetes, especially if they are current
      injection users or are dissatisfied with their current treatments or outcomes.
      Greater convenience, better medication adherence and improved QOL are commonly
      endorsed attributes. Clinicians may need to review both the positive attributes
      of QW medications as well as common patient concerns, when considering this
      option.

PMID- 21199265
TI  - Effects of colesevelam on LDL-C, A1c and GLP-1 levels in patients with type 1
      diabetes: a pilot randomized double-blind trial.
AB  - AIM: colesevelam is indicated to lower low density lipoprotein cholesterol (LDL
      C) in hyperlipidaemia and improve glycaemic control in adults with type 2
      diabetes. This short-term pilot study evaluates its effects in type 1 diabetes.
      METHODS: this double-blind, randomized, investigator-initiated, single-centred,
      12-week pilot study evaluated 40 adults (age = 36.4 +/- 9.4 years) with type 1
      diabetes (duration = 20.4 +/- 8.5 years) and hyperlipidaemia. It was powered to
      show a treatment difference of >10% LDL-C reduction. Subjects received 3.75 g/day
      colesevelam (n = 20) or placebo (n = 20) for 12 weeks. LDL-C and haemoglobin A1c
      (A1c) levels were assessed at screening (week 2), baseline (week 0) and every 4
      weeks throughout the treatment duration. Glucagon-like peptide-1 (GLP-1) and
      glucose-dependent insulinotropic peptide (GIP) levels were measured during 4-h
      meal (Boost Plus, Nestle HealthCare Nutrition Inc., Florham Park, New Jersey,
      USA) challenge tests (MCT) at baseline and 12 weeks. RESULTS: colesevelam
      treatment resulted in a significant reduction in LDL-C values at 4 weeks [-12.1%
      (95% CI: -20.1 to -4.1), p = 0.004] which was sustained for the study duration (p
      = 0.005 at 12 weeks). The treatment group also showed a significant change in A1c
      from baseline at week 4; however, this was not significant for the study
      duration. There was a significant median increase in GLP-1 levels during the
      first 2 h of the baseline MCT in the treated group but no difference at 12 weeks.
      CONCLUSIONS: during this short-term pilot study, colesevelam treatment
      effectively lowered LDL-C in patients with type 1 diabetes. Improvements in A1c
      seen at week 4 were not sustained. Effects on glycaemic control in subjects with
      type 1 diabetes may be related to a postprandial rise in GLP-1 levels and require
      further clinical study.

PMID- 21199267
TI  - Minocycline completely reverses mechanical hyperalgesia in diabetic rats through
      microglia-induced changes in the expression of the potassium chloride co
      transporter 2 (KCC2) at the spinal cord.
AB  - AIM: neuronal hyperactivity at the spinal cord during mechanical hyperalgesia
      induced by diabetes may result from a decrease in the local expression of the
      potassium chloride co-transporter 2 (KCC2), which shifts the action of the
      neurotransmitter gamma-amminobutiric acid (GABA) from inhibitory to excitatory.
      In this study, we evaluated the effects of spinal microglia inhibition or brain
      derived neurotrophic factor (BDNF) blockade on KCC2 expression, spinal neuronal
      activity and mechanically induced pain responses of streptozotocin (STZ)-diabetic
      rats. METHODS: four weeks after induction of diabetes, the STZ-diabetic rats
      received daily intrathecal injections, for 3 days, of minocycline (microglia
      inhibitor), TrkB/Fc (BDNF sequester) or saline. Behavioural responses to
      mechanical nociceptive stimulation of STZ-diabetic rats were evaluated by the
      Randall-Selitto test. The lumbar spinal cord was immunoreacted against the Fos
      protein (marker of neuronal activation) or KCC2, which was also quantified by
      western blotting. BDNF levels at the spinal cord were quantified by an enzyme
      linked immunosorbent assay (ELISA). RESULTS: minocycline treatment reversed the
      mechanical hyperalgesia, increased Fos expression and decreased the KCC2
      expression detected in STZ-diabetic rats to control levels. Treatment with
      TrkB/Fc was less effective, inducing moderate effects in mechanical hyperalgesia
      and Fos expression and only a partial correction of KCC2 expression. BDNF levels
      were not increased in STZ-diabetic rats. CONCLUSIONS: this study demonstrates
      that the microglial activation at the spinal cord contributes to mechanical
      hyperalgesia and spinal neuronal hyperactivity induced by diabetes, apparently by
      regulating the KCC2 expression. These effects do not seem to be mediated by BDNF,
      which is an important difference from other chronic pain conditions. New targets
      directed to prevent spinal microglia activation should be considered for the
      treatment of mechanical hyperalgesia induced by diabetes.

PMID- 21199268
TI  - Efficacy and safety of treatment with sitagliptin or glimepiride in patients with
      type 2 diabetes inadequately controlled on metformin monotherapy: a randomized,
      double-blind, non-inferiority trial.
AB  - AIM: to evaluate the efficacy and safety of adding sitagliptin or glimepiride to
      the treatment regimen of patients with type 2 diabetes mellitus and inadequate
      glycaemic control on metformin monotherapy. METHODS: patients with type 2
      diabetes and an HbA(1c) of 6.5-9.0% while on a stable dose of metformin (>= 1500
      mg/day) combined with diet and exercise for at least 12 weeks were randomized in
      a double-blind manner to receive either sitagliptin 100 mg daily (N = 516) or
      glimepiride (starting dose 1 mg/day and up-titrated, based upon patient's self
      monitoring of blood glucose results, to a maximum dose of up to 6 mg/day) (N =
      519) for 30 weeks. The primary analysis assessed whether sitagliptin is non
      inferior to glimepiride in reducing HbA(1c) at week 30 (based on the criterion of
      having an upper bound of the 95% CI less than the prespecified non-inferiority
      bound of 0.4%). RESULTS: the mean baseline HbA(1c) was 7.5% in both the
      sitagliptin group (n = 443) and the glimepiride group (n = 436). After 30 weeks,
      the least squares (LS) mean change in HbA(1c) from baseline was -0.47% with
      sitagliptin and -0.54% with glimepiride, with a between-group difference (95% CI)
      of 0.07% (-0.03, 0.16). This result met the prespecified criterion for declaring
      non-inferiority. The percentages of patients with an HbA(1c) < 7.0% at week 30
      were 52 and 60% in the sitagliptin and glimepiride groups, respectively. The LS
      mean change in fasting plasma glucose from baseline (95% CI) was -0.8 mmol/l (
      1.0, -0.6) with sitagliptin and -1.0 mmol/l (-1.2, -0.8) with glimepiride, for a
      between-group difference (95% CI) of 0.2 mmol/l (-0.1, 0.4). The percentages of
      patients for whom hypoglycaemia was reported were 7% in the sitagliptin group and
      22% in the glimepiride group (percentage-point difference = -15, p < 0.001).
      Relative to baseline, sitagliptin was associated with a mean weight loss (-0.8
      kg), whereas glimepiride was associated with a mean weight gain (1.2 kg),
      yielding a between-group difference of -2.0 kg (p < 0.001). CONCLUSIONS: in
      patients with type 2 diabetes and inadequate glycaemic control on metformin
      monotherapy, the addition of sitagliptin or glimepiride led to similar
      improvement in glycaemic control after 30 weeks. Sitagliptin was generally well
      tolerated. Compared to treatment with glimepiride, treatment with sitagliptin was
      associated with a lower risk of hypoglycaemia and with weight loss versus weight
      gain (ClinicalTrials.gov: NCT00701090).

PMID- 21199269
TI  - The effect of pramlintide acetate on glycemic control and weight in patients with
      type 2 diabetes mellitus and in obese patients without diabetes: a systematic
      review and meta-analysis.
AB  - AIM: the objective of this systematic review and meta-analysis was to assess the
      effect of pramlintide on glycemic control, weight and incidence of nausea and
      hypoglycaemia in patients with type 2 diabetes mellitus (T2DM) and in obese
      patients without diabetes (OBP). METHODS: eight randomized, clinical trials were
      identified from multiple databases. Qualitative assessments and quantitative
      analyses were performed. RESULTS: in four T2DM studies (N = 930,duration of
      studies 16-52 weeks,120-150 mcg/dose BID-TID), all patients received insulin
      therapy. In four obesity studies (N = 686,duration of studies 6-24 weeks,120-360
      mcg/dose BID-TID), equivalent volumes of placebo were administered before major
      meals. Pramlintide significantly reduced haemoglobin A1c (HbA1c) (-0.33% [95% CI 
      0.51, -0.14], p = 0.004) and weight (-2.57 kg, [95% CI -3.44, -1.70], p <
      0.00001) versus the control group. More patients in the control group reported
      hypoglycaemia of any severity versus the pramlintide group (risk ratio 0.84 [95%
      CI 0.69, 10.3], p = 0.09). In OBP, pramlintide caused a reduction in weight (
      2.27 kg [95% CI -2.88, -1.66], p < 0.00001). When event data from both
      populations were combined, patients randomized to pramlintide were 1.8 times more
      likely to report nausea of any severity versus control (p = 0.0005). CONCLUSIONS:
      pramlintide was associated with a small reduction in HbA1c, and a modest
      reduction in weight in patients with T2DM or OBP. There was increased incidence
      of nausea but not hypoglycaemia at any time during therapy. Studies about the
      long-term effect of pramlintide on diabetes- and cardiovascular-related
      complications and cost-effectiveness analyses are needed.

PMID- 21199270
TI  - Phosphoprotein enriched in diabetes gene product (Ped/pea-15) is increased in
      omental adipose tissue of women with the polycystic ovary syndrome: ex vivo
      regulation of ped/pea-15 by glucose, insulin and metformin.
AB  - Polycystic ovary syndrome (PCOS), the commonest endocrine disorder in women, is
      characterized by an altered steroid milieu and is associated with insulin
      resistance and type 2 diabetes mellitus (T2DM). Phosphoprotein enriched in
      diabetes gene product (Ped/pea-15) regulates glucose metabolism and is increased
      in T2DM. Our novel data indicate that Ped/pea-15 mRNA expression and protein
      levels are significantly increased in omental adipose tissue (AT) from PCOS women
      compared to matched controls (p < 0.01); Ped/pea-15 levels in subcutaneous AT
      were not significantly different. Furthermore, Ped/pea-15 mRNA expression and
      protein levels were higher in omental compared to subcutaneous AT in PCOS
      subjects (p < 0.01); however, in control subjects, this was not significant.
      Glucose was predictive of omental AT Ped/pea-15 mRNA expression (p = 0.045).
      Importantly, glucose and insulin increased whereas metformin significantly
      decreased Ped/pea-15 levels in human omental AT explants. Our findings should
      serve to promote further research on Ped/pea-15 biology.

PMID- 21199271
TI  - Can sulphonylurea addition to lifestyle changes help to delay diabetes
      development in subjects with impaired fasting glucose? The Nepi ANtidiabetes
      StudY (NANSY).
AB  - The Nepi ANtidiabetes StudY (NANSY) is a 5-year randomized, double-blind, placebo
      controlled trial in Swedish primary care, examining whether the development of
      type 2 diabetes (T2D) and retinopathy (separately reported) would be delayed in
      40- to 70-year-old subjects with impaired fasting glucose (IFG) who, in addition
      to lifestyle changes, were treated with either placebo or low-dosage
      sulphonylurea (SU) (1-mg glimepiride; Amaryl). Of 274 subjects (163 men, 111
      women), 138 were allocated to placebo (46.0% men, 56.8% women) and 136 to
      glimepiride (54.0% men, 43.2% women). The primary endpoint was conversion to
      diabetes. Average follow-up time was 3.71 years; 96 subjects converted to
      diabetes, 55 allocated to placebo and 41 to glimepiride (absolute difference
      9.8%; p = 0.072). In conclusion, the study failed to support the notion that low
      dose SU added to lifestyle changes in IFG subjects would help to delay the
      conversion to diabetes.

PMID- 21199272
TI  - Regional fat changes following weight reduction from laparoscopic Roux-en-Y
      gastric bypass surgery.
AB  - Fat accumulation in muscle (intermuscular, IM) and viscera plays a role in
      obesity comorbidities. This study examined the impact of Roux-en-Y gastric bypass
      (RYGB) surgery in morbid obesity on changes in regional fat and muscle depots,
      and these body composition markers were correlated with physical function. Women
      (n = 18) were assessed prior to (baseline) and 12 months following RYGB for
      regional body composition and physical function. Weight loss from baseline to 12
      months was 33.7 (s.e.m. = 1.7)%; total body fat decreased from 86.8 (s.e.m. =
      5.8) to 45.8 (s.e.m. = 3.9) kg during follow-up. Differential changes in regional
      body fat were apparent with a volume loss of 58.4% in visceral fat, 19.8% in
      abdomen IM fat and 50.7% in thigh IM fat. At baseline, abdomen IM fat volume was
      related to physical function. There was less loss of abdomen IM fat volume than
      other depots following surgery; furthermore its relationship with physical
      function is a novel finding.

PMID- 21199273
TI  - Acceptance of a 5-mm distal bowel resection margin for rectal cancer: is it safe?
AB  - AIM: Acceptance of a short distal bowel margin results in a higher rate of
      anterior resection but may compromise oncological safety. This study aimed to
      evaluate the safety of a 5-mm distal margin. METHOD: A retrospective analysis was
      carried out of 412 consecutive patients with rectal cancer treated with anterior
      resection with a negative circumferential resection margin. Radiotherapy was
      given to 63% of patients with an advanced tumour. The median follow up was 75
      months. RESULTS: Fewer patients in the group with a distal margin of <= 5 mm had
      a tumour with an advanced pT stage compared to patients in the group with a
      distal margin of > 5 mm (P = 0.033). Two patients were converted to
      abdominoperineal resection because of a positive 'doughnut', leaving 410
      patients, in whom 5.4% (95% CI, 0-11.3%) of the group with a distal margin of <=
      5 mm had local recurrence at 5 years compared with 4.2% (95% CI, 2.1-6.3%) of the
      group with a distal margin of > 5 mm (P = 0.726). The corresponding figures for
      the 5-year overall survival were 82.4% (95% CI, 72.6-92.2%) vs 76.3% (95% CI,
      71.8-80.8%) (P = 0.581). All four anastomotic recurrences occurred in the group
      with a distal margin of > 5 mm. CONCLUSION: A distal margin of <= 5 mm did not
      compromise oncological safety in patients undergoing preoperative radiation for
      an advanced rectal cancer.

PMID- 21199274
TI  - In vivo confocal microscopy of equine fungal keratitis.
AB  - OBJECTIVE: To describe in vivo corneal confocal microscopy of horses with fungal
      keratitis and correlate findings with clinical, histopathological, and
      microbiological evaluations of clinical cases and an ex vivo experimental equine
      fungal keratitis model. ANIMALS STUDIED: A total of 12 horses with naturally
      acquired fungal keratitis and ex vivo equine corneas experimentally infected with
      clinical fungal isolates. PROCEDURES: Horses with naturally-acquired fungal
      keratitis were examined with a modified Heidelberg Retina Tomograph II and
      Rostock Cornea Module. Confocal microscopy images of clinical isolates of
      Aspergillus fumigatus, Fusarium solani, and Candida albicans were obtained by
      examination of in vitro cultures and experimentally infected ex vivo equine
      corneas. RESULTS: Non-specific in vivo corneal confocal microscopic findings in
      horses with fungal keratitis included leukocyte infiltrates, activated
      keratocytes, anterior stromal dendritic cell infiltrates, and vascularization.
      Linear, branching, hyper-reflective structures that were 2-6 MUm in width and 200
      to >400 MUm in length were detected in all horses with filamentous fungal
      keratitis. Round to oval hyper-reflective structures that were 2-8 MUm in
      diameter were detected in a horse with yeast fungal keratitis. The in vivo
      confocal microscopic appearance of the organisms was consistent with fungal
      morphologies observed during examination of in vitro cultures and infected ex
      vivo equine corneas. CONCLUSIONS: In vivo corneal confocal microscopy is a rapid
      and non-invasive method of diagnosing fungal keratitis in the horse. This imaging
      technique is useful for both ulcerative and non-ulcerative fungal keratitis, and
      is particularly advantageous for confirming the presence of fungi in deep corneal
      stromal lesions.

PMID- 21199275
TI  - Spiroplasma found in the eyes of scrapie affected sheep.
AB  - OBJECTIVE: Scrapie, a transmissible spongiform encephalopathy (TSE) occurring
      naturally in sheep, characteristically shows a severe retinopathy that is well
      developed in the terminal phases of the disease. In this study, we set out to
      demonstrate similar retinal changes in our ruminant spiroplasmosis TSE model.
      PROCEDURE: The eyes from deer, sheep, and goats that were inoculated
      intracranially with the laboratory strain of spiroplasma (suckling mouse cataract
      [SMCA] strain of Spiroplasma mirum) or with Spiroplasma sp. isolated from the
      brains affected with scrapie or with chronic wasting disease were examined by
      light microscopy for pathologic changes and by immunocytochemistry for
      distribution of spiroplasma antigen. The eyes were also obtained from a research
      flock of sheep with terminal scrapie, from which the intraocular tissues were
      submitted aseptically for culture assay in M1D broth or as explants on bovine
      corneal endothelia (BCE). RESULTS: The eyes from the spiroplasmosis ruminant
      models showed retinopathy remarkably similar to eye lesions seen in sheep with
      scrapie. The spiroplasma antigen accrued in the ruminant model eye tissues,
      particularly in the retina, the vitreous humor, and the corneal endothelia. A
      Spiroplasma sp. grew out of the scrapie-affected eyes both in the M1D broth and
      in the BCE cultures but did not expand. These new spiroplasma isolates differed
      immunologically from SMCA. CONCLUSION: These data showed a clear association of
      spiroplasma with scrapie suggesting that these bacteria have a role in the
      pathogenesis of TSE and that the eye should be a research focus for future
      studies of TSE.

PMID- 21199276
TI  - Efficacy of topically applied liposome-bound tetracycline in the treatment of dry
      eye model.
AB  - OBJECTIVE: To evaluate the effects of liposome-bound tetracycline eye drops in a
      rabbit dry eye model evaluating their advantage of being less allergic,
      preservative free and prolonged action compared with other tear substitutes.
      PROCEDURES: New Zealand albino rabbits were equally divided into control group
      and dry eye induced groups. Dryness was induced in 24 eyes of 12 healthy adult
      male albino rabbits by instilling atropine sulfate eye drops 1% three times daily
      for 1 week, then animals were subdivided into four groups; group 1 (rabbits with
      dry eye model), groups 2, 3, and 4: rabbits with dry eye model treated for 7 days
      starting on 7th day of dryness induction with either tetracycline, empty
      liposome, or combined tetracycline with liposome as topical eye drops
      respectively. Schirmer (STT) test and tear break up time (TBUT) were assessed on
      days 0, 2, 4, 7, 9, 11, and 14. Animals were sacrificed on day 14 and
      histopathological examination of the cornea and conjunctiva was performed.
      RESULTS: Tear break up time and STT test values were significantly improved in
      groups 2, 3, 4 as compared with group 1. The histopathological examination showed
      normal cytoarchitecture of corneas and conjunctivae in groups 2, 3, 4 against the
      dryness effect that continued to affect the cornea and conjunctival epithelium in
      group 1. There was a significant improvement in the group treated with liposome
      bound tetracycline eye drops (group 4) as compared with tetracycline alone (group
      2) and empty liposome (group 3). CONCLUSION: The use of liposome encapsulated
      tetracycline significantly improved STT and TBUT values as well as reverse
      surface ocular pathology.

PMID- 21199277
TI  - Investigations on the conjunctival goblet cells and on the characteristics of
      glands associated with the eye in the guinea pig.
AB  - OBJECTIVE: To investigate the distribution and density of conjunctival goblet
      cells (GC) and to study the anatomy and microscopic characteristics of glands
      associated with the eye in the guinea pig. PROCEDURES: Twenty-five guinea pigs
      were used. Meibomian gland openings were counted using biomicroscopy.
      Conjunctiva, eyelids and glands were embedded in glycol methacrylate and
      paraffin. Sections were stained with hematoxylin and eosin (H&E), periodic acid
      Schiff's reaction (PAS) and Alcian blue (AB). RESULTS: Highest GC densities were
      found in the bulbar and palpebral region of the nasal conjunctiva (GC index: 13.7
      16.4%). Lowest GC densities (GC index: 0.0-1.0%) were found in 3/4 limbal regions
      (nasal and temporal upper eyelid, temporal lower eyelid). Guinea pigs have 27.1+/
      3.0 (mean+/-SD) meibomian gland openings in the upper lid and 25.7+/-2.3 in the
      lower lid. Difference between upper and lower lid was significant (P=0.037). Two
      subconjunctival sebaceous glands occur temporal to each eye. The Harderian gland
      is very large. In the lacrimal gland three different cell types were
      distinguished both according to the cell structure and histochemical staining.
      CONCLUSIONS: Goblet cell densities are lower in guinea pigs than in dogs and
      horses. Positive staining with PAS and AB could be an indication that mucins are
      produced in the lacrimal gland. If so, they may contribute to the mucin layer of
      the tear film. Both the extraordinarily large Harderian gland and the
      subconjunctival sebaceous glands produce lipids and may contribute to the lipid
      layer of the tear film.

PMID- 21199278
TI  - Aqueous humor and plasma concentrations of a compounded 0.2% solution of
      terbinafine following topical ocular administration to normal equine eyes.
AB  - OBJECTIVE: To determine the transcorneal penetration and systemic absorption of a
      compounded 0.2% terbinafine solution following repeated topical administration to
      normal equine eyes. Sample population  Six healthy adult horses with normal
      ocular examinations. PROCEDURES: One eye of each horse received 0.2 mL of a
      compounded 0.2% terbinafine solution every 4 h for seven doses. During the 1 h
      following administration of the final dose, multiple peripheral blood samples
      were obtained, and a single aqueous humor (AH) sample was collected at the end of
      the hour. AH and plasma concentrations of terbinafine were determined using high
      pressure liquid chromatography (HPLC). Stability of the formulation was assessed
      with HPLC analysis over a 14-day time period. RESULTS: Terbinafine was not
      detected in the AH or plasma of any horse at any time point. No signs of ocular
      irritation or systemic toxicity were noted in any horse at any time point. The
      solution was stable over 14 days. CONCLUSION: Topical ocular administration of
      compounded 0.2% terbinafine solution does not result in detectable AH or plasma
      levels following administration to normal equine eyes, suggesting its use for
      deep corneal or intraocular fungal infections in equine ophthalmology may be
      limited.

PMID- 21199279
TI  - Primary lacrimal gland adenocarcinoma of the third eyelid in a horse.
AB  - A 5-year-old Draft Horse gelding presented for evaluation of a large, fleshy,
      ulcerated third eyelid mass OD of 3 weeks duration. Complete ophthalmic
      examination, ocular ultrasound and skull radiographs revealed a large soft-tissue
      mass involving the entire third eyelid OD and extending into the ventral right
      orbit to the level of the globe equator. No other abnormalities were noted on
      physical or ophthalmic examination. Surgical removal via exenteration was
      performed 3 months after initial presentation. A lacrimal adenocarcinoma of the
      third eyelid was diagnosed based on histopathology. Concurrent asymptomatic intra
      ductal and intra-acinar Demodex caballi parasites were found in the eyelid
      sebaceous glands, likely as an incidental finding. No tumor recurrence or
      metastasis has occurred 12 months after excision. To the author's knowledge, this
      case is the first reported primary lacrimal adenocarcinoma in a horse. Complete
      surgical excision was curative.

PMID- 21199280
TI  - Unilateral orbital lacrimal gland abscess in a horse.
AB  - A 20-year-old Thoroughbred gelding presented for evaluation of a periorbital
      dorsal swelling of the left eye that had been intermittently present for 3
      months. Upon ocular examination, a firm, non-painful swelling was identified
      under the upper eyelid in the region of the orbital lacrimal gland, and was noted
      to extend anteriorly from underneath the dorsal orbital rim. Ultrasonographic
      examination revealed a mixed echogenic mass along the dorsal orbital rim that
      followed the contour of the globe. CT scan showed a moderately contrast enhancing
      mass that was contiguous with the eyelid. Differential diagnoses included
      neoplasia, inflammatory lesions such as a granuloma, foreign body or abscess.
      Surgical exploration and excision of the mass revealed a lobular structure with a
      purulent center. Histopathology identified the mass as the orbital lacrimal gland
      with concurrent severe dacryoadenitis. Culture of the purulent center of the mass
      revealed beta-hemolytic Staphylococcus aureus. The patient was maintained on
      supportive care and antibiotic treatment based on sensitivity postoperatively. No
      recurrence was reported 40 months later. This paper aims to identify bacterial
      dacryoadenitis as a cause for unilateral periorbital swelling in the horse.
      Differential diagnoses for this presentation, as well as successful surgical
      management are discussed. To the author's knowledge, this is the first case of
      bacterial dacryoadenitis and subsequent abscessation of the orbital lacrimal
      gland in the horse.

PMID- 21199281
TI  - Mucosa-associated lymphoid tissue lymphoma of the third eyelid conjunctiva in a
      dog.
AB  - A 4-year-old, neutered female Cocker Spaniel was presented to the veterinary
      clinic for protrusion of the left third eyelid. When the third eyelids from both
      eyes were everted, lobulated masses were present on the bulbar surface. The left
      third eyelid had a larger protrusion. There was no apparent associated ocular or
      systemic involvement. The tumor of left third eyelid was removed and referred for
      histological examination. Histologically, there were proliferations of lymphoid
      follicles surrounded by lymphoid cells forming a marginal zone. Those lymphoid
      cells occasionally infiltrated into conjunctival epithelium. A few apoptotic
      bodies with karyopyknotic and karyorrhexic nuclei were observed in the germinal
      center of lymphoid follicles. Mitotic figures were rare. On immunohistochemistry,
      tumor cells expressed CD79a but not CD3. A diagnosis of extranodal marginal zone
      B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) of the third eyelid
      was established based on the histological and immunophenotypical features. At the
      1-year follow-up, there was no evidence of recurrence of the mass at the area of
      excision of the left third eyelid and the remaining tumor of the right third
      eyelid was still a similar size. The dog still showed no significant findings,
      except those of the tumor, and no evidence of systemic involvement. To the
      authors' knowledge, this is the first reported case of MALT lymphoma of the third
      eyelid in a dog.

PMID- 21199282
TI  - Suitability and calibration of a rebound tonometer to measure IOP in rabbit and
      pig eyes.
AB  - OBJECTIVE: To utilize the Icare tonometer TAO1 for intraocular pressure (IOP)
      determination in experimental animals. To calculate true IOP calibration
      functions for rabbit and porcine eyes. ANIMALS: Enucleated eyes of 3-year-old
      healthy experimental rabbits (New Zealand white), and healthy 1 year old
      experimental pigs (Deutsche Landrasse) were used for the determination of IOP.
      PROCEDURES: Manometric (Geuder GmbH, Heidelberg/Germany) and rebound tonometry
      (Icare tonometer TAO1, Icare, Helsinki/Finland) were used to record IOP in
      enucleated animal eyes (rabbit n=2, pig n=3). RESULTS: The Icare tonometer TAO1
      measurements underestimated true IOP by 37-60% in rabbit eyes and 17-63% in
      porcine eyes. IOP values obtained by both rebound and manometric tonometry for
      rabbit and porcine eyes followed a linear regression curve. Linear functions were
      calculated to correct the Icare tonometer TAO1 measurements to true IOP for both
      rabbit (p=1.4244p(ic) + 4.2421) and porcine eyes (p=1.0799p(ic) + 5.8557).
      CONCLUSIONS: The Icare tonometer TAO1 can be utilized for IOP determination in
      rabbit and porcine eyes when measured values are corrected with the appropriate
      linear function.

PMID- 21199283
TI  - In response to the paper, Calcareous degeneration of the canine cornea.

PMID- 21199284
TI  - Extending the indications and anatomical limits of pelvic lymph node dissection
      for prostate cancer: improved staging or increased morbidity?
AB  - OBJECTIVE: * To assess, in a risk/benefit analysis, the additional risk for
      complications and benefits of extending the indications and anatomical limits of
      pelvic lymph node dissection (PLND). PATIENTS AND METHODS: * In total, 971
      consecutive patients with clinically localized prostate cancer underwent
      laparoscopic radical prostatectomy from 2003-2007. * Before 1 February 2005,
      patients with a nomogram probability of lymph node invasion (LNI) <2% did not
      undergo PLND (No PLND group), whereas those with a LNI >= 2% had a PLND limited
      to the external iliac nodal group (limited PLND group). * After 1 February 2005,
      all patients underwent a standard PLND including the external iliac, hypogastric
      and obturator fossa nodal groups (standard PLND group). * The risk parameters
      were PLND-related complications and operating time. Complications were graded
      using a modified Clavien classification. The benefit was the detection of nodal
      metastases. RESULTS: * In the subgroup of patients with a LNI >= 2%, standard
      PLND was a superior operation than the limited PLND in detecting nodal metastases
      (14.3% vs 4.5%, respectively; P = 0.003). * The risk/benefit of standard vs
      limited PLND would be one additional grade 3 complication per 20 additional
      patients with nodal metastases. In the subgroup of patients with LNI <2%, three
      patients (1.0%) had positive nodes after a standard PLND. * The risk/benefit of
      standard PLND vs no PLND would be one additional grade 3 complication per three
      or four additional patients with nodal metastasis. The no PLND group was
      associated with the lowest risk of grade 1, 2 and 3 complications compared to
      either the limited or standard PLND groups (P < 0.001). CONCLUSIONS: * In
      patients with LNI >= 2%, standard PLND detects more nodal metastasis. PLND is
      associated with higher but non-prohibitive complications rate. * The present
      study found no evidence that the incidence of complications would be reduced by a
      limited PLND.

PMID- 21199285
TI  - Are men on 5alpha-reductase inhibitors appropriately referred to urology? A
      survey of primary care physicians.
AB  - OBJECTIVE: * To investigate among general practitioners (GPs) their level of
      awareness and indications for urological consultations in patients treated with
      5alpha-reductase inhibitors (5ARIs). SUBJECTS AND METHODS: * We conducted a
      survey of GPs in Quebec. * Questions covered GPs' preferred benign prostatic
      hyperplasia (BPH) management, knowledge of 5ARIs, their role in prostate cancer
      prevention, and triggers for urology consultation. RESULTS: * Of the surveys
      mailed, 599 were returned (15.7% response rate). * Therapy with 5ARIs was
      initiated by GPs in 34.3%, with 20% and 12% preferring 5ARIs alone and combined
      with an alpha-blocker as first-line therapy for BPH, respectively. * Once on
      therapy, 74% did not refer to a urologist if the PSA level did not decline after
      6-12 months. * Finally, 40.7% would not advocate 5ARI chemoprevention for
      prostate cancer, regardless of risk reduction. * Findings were not associated
      with GP gender, experience or geographic location of practice (urban versus
      rural). CONCLUSIONS: * There was a preference amongst GP to use alpha-blockers
      over 5ARIs for BPH and hesitancy to use them in prostate cancer chemoprevention.
      * There is a lack of awareness of 5ARI effects on PSA kinetics and a reluctance
      to refer to a urologist. * Further education in Quebec is needed about 5ARIs to
      optimize their usage and avoid delaying cancer detection.

PMID- 21199286
TI  - Laparoscopic partial nephrectomy for multiple tumours: feasibility and analysis
      of peri-operative outcomes.
AB  - OBJECTIVE: * To describe our experience with laparoscopic partial nephrectomy
      (LPN) for multiple kidney tumours and compare the outcomes with LPN performed for
      single masses. PATIENTS AND METHODS: * Retrospective analysis of medical records
      of patients undergoing LPN at our institution between 2005 and 2009 was
      performed. * The cohort was divided in two groups based on tumour focality: group
      1, LPN for a single tumour (n= 99) and group 2, LPN for multiple ipsilateral
      tumours (n= 12). * The groups were compared with regards to demographic and peri
      operative variables. RESULTS: * Demographic variables were not different between
      the groups. Median dominant tumour size was 3.1 cm (interquartile range [IQR] 2.4
      4.0) and 4.0 cm (2.3-5.9) in groups 1 and 2, respectively. * Median secondary
      tumour size in group 2 was 1.0 cm (1.0-1.8). * Operative times were longer in
      group 2 compared with group 1 (220 vs 160 min, P= 0.009). * Warm ischaemia times
      (WIT) (23 vs 22 min) and estimated blood loss (EBL) (100 vs 85 mL) were similar.
      CONCLUSIONS: * LPN is a viable option for the treatment of multiple ipsilateral
      renal tumours. * Peri-operative outcomes are similar to standard LPN with the
      exception of longer operative time. * In experienced hands, the advantages of
      minimally invasive surgery may be extended to select patients with ipsilateral
      multifocal renal tumours.

PMID- 21199287
TI  - Prediction of pathological outcomes for a single microfocal (<=3 mm) Gleason 6
      prostate cancer detected via contemporary multicore (>=12) biopsy in men with
      prostate-specific antigen <=10 ng/mL.
AB  - OBJECTIVE: * To examine potential predictors of pathological outcomes for a
      single microfocal (<=3 mm) positive prostate cancer detected via contemporary
      biopsy scheme in patients presenting with prostate-specific antigen (PSA) <=10
      ng/mL. PATIENTS AND METHODS: * We reviewed the data of 119 patients who had
      prebiopsy PSA <= 10 ng/mL and a single microfocal (<=3 mm) Gleason <=6 prostate
      cancer identified via multicore (>=12) biopsy and who subsequently underwent
      radical prostatectomy (RP). * We assessed the rates of insignificant prostate
      cancer (organ-confined and pathological Gleason <=6 with tumour volume <0.5 mL)
      and unfavourable prostate cancer (upstaging and/or upgrading) by analysing
      pathological findings. * Potential preoperative predictors of insignificant or
      unfavourable prostate cancer were analysed. Multivariable models for predicting
      insignificant and unfavourable tumours were devised and evaluated. RESULTS: *
      Overall rates of insignificant and unfavourable prostate cancer were 44.5% and
      24.4%, respectively. In multivariate analysis, only PSA density was an
      independent predictor of insignificant prostate cancer. * Predictive accuracies
      of multivariable models for predicting insignificant prostate cancer did not
      exceed 68.2%. No significant predictor for pathologically unfavourable tumour was
      found in multivariate analysis. * All versions of the multivariable model devised
      for prediction of unfavourable tumour showed predictive accuracies <=66.9%.
      CONCLUSION: * Although PSA density can be considered an independent predictor of
      pathologically insignificant tumour among patients with PSA <=10 ng/mL and only a
      single microfocal tumour detected via multicore (>=12) biopsy, the clinical and
      biopsy-related parameters that are currently available have limited value in
      predicting pathologically insignificant or unfavourable prostate cancer in such
      patients.

PMID- 21199288
TI  - Evaluating the life-history trade-off between dispersal capability and
      reproduction in wing dimorphic insects: a meta-analysis.
AB  - A life-history trade-off exists between flight capability and reproduction in
      many wing dimorphic insects: a long-winged morph is flight-capable at the expense
      of reproduction, while a short-winged morph cannot fly, is less mobile, but has
      greater reproductive output. Using meta-analyses, I investigated specific
      questions regarding this trade-off. The trade-off in females was expressed
      primarily as a later onset of egg production and lower fecundity in long-winged
      females relative to short-winged females. Although considerably less work has
      been done with males, the trade-off exists for males among traits primarily
      related to mate acquisition. The trade-off can potentially be mitigated in males,
      as long-winged individuals possess an advantage in traits that can offset the
      costs of flight capability such as a shorter development time. The strength and
      direction of trends differed significantly among insect orders, and there was a
      relationship between the strength and direction of trends with the relative
      flight capabilities between the morphs. I discuss how the trade-off might be both
      under- and overestimated in the literature, especially in light of work that has
      examined two relevant aspects of wing dimorphic species: (1) the effect of flight
      muscle histolysis on reproductive investment; and (2) the performance of actual
      flight by flight-capable individuals.

PMID- 21199289
TI  - Risk of synechiae following uterine compression sutures in the management of
      major postpartum haemorrhage.
AB  - OBJECTIVE: To determine with hysteroscopy or hysterosalpingogram the risk of
      uterine synechiae following uterine compression sutures for major postpartum
      haemorrhage (PPH) caused by uterine atony. DESIGN: A retrospective observational
      study. SETTING: Department of Obstetrics and Gynaecology, Beaujon Hospital,
      Clichy, France. POPULATION: One hundred and ninety-seven women with PPH between
      2007 and 2010. One hundred and thirteen women (57.4%) were transferred as an
      emergency to our institution from other centres. METHODS: Of the 197 women, 94
      with PPH had uterine arterial embolisation and 33 with major PPH were managed
      with surgical uterine compression sutures (Hackethal technique). The women were
      invited to undergo a control hysteroscopy or hysterosalpingogram, after
      postpartum consultation, to assess the uterine cavity. MAIN OUTCOME MEASURE: The
      prevalence of subsequent uterine synechiae. RESULTS: Uterine compression sutures
      succeeded in controlling PPH in 26 of 33 women (78.8%). Seven needed a
      hysterectomy. Among women with a preserved uterus, 15 underwent an exploration of
      the uterine cavity, including hysteroscopy (12) or hysterosalpingogram (8). Four
      women (26.7%) developed uterine synechiae and one had a subsequent pregnancy 18
      months after uterine compression sutures. The median time between delivery and
      hysteroscopy or hysterosalpingogram was 9.3 months (2.4-34.8 months).
      CONCLUSIONS: This study suggests a significant risk of uterine synechiae after
      placement of compression sutures for PPH that transverse the uterine cavity.
      Postoperative uterine synechiae might be underestimated, and their prevalence and
      clinical significance should be assessed in long-term follow-up studies.

PMID- 21199290
TI  - The effect of misoprostol on postpartum contractions: a randomised comparison of
      three sublingual doses.
AB  - OBJECTIVE: To compare the postpartum uterine activity and side effects of various
      doses of sublingual misoprostol and intramuscular oxytocin. DESIGN: Single
      centre, randomised trial. SETTING: Zliten Teaching Hospital in Libya. POPULATION:
      Forty-nine women who did not receive oxytocics in labour and who delivered
      vaginally. METHODS: Thirty-five women were randomised to receive 200, 400 or 600
      mcg of sublingual misoprostol PPH prophylaxis immediately following delivery.
      These were compared with 14 consecutive women given 10 IU of intramuscular
      oxytocin. Immediately after placental delivery, a Koala intra uterine pressure
      catheter was inserted transcervically into the uterine cavity. MAIN OUTCOMES
      MEASURES: Main outcomes measures are the uterine pressure (in Montevideo units)
      measured over 120 minutes. Other outcomes included temperature and measured blood
      loss. RESULTS: Women's age, parity, gestational age and neonatal birth weight
      were not significantly different between the four groups. There was no difference
      in intrauterine pressure between the three misoprostol doses. However, the
      uterine pressure was significantly lower than oxytocin with all three doses for
      the first 10 minutes (P < 0.008) and significantly higher than oxytocin from 50
      to 120 minutes (P < 0.008). A dose-related rise in the body temperature and
      chills was observed in the misoprostol groups, with 8.3%, 8.3% and 45% of women
      experiencing a fever >39  degrees C with the 200, 400, and 600 mcg doses
      respectively. CONCLUSION: Intramuscular oxytocin has the highest immediate post
      partum uterine activity. Lower doses of misoprostol may be as effective as high
      doses and with fewer side effects. Clinical outcomes with low-dose misoprostol
      should be further explored (ISRCTN97277056).

PMID- 21199291
TI  - Prognostic markers of symptomatic congenital human cytomegalovirus infection in
      fetal blood.
AB  - OBJECTIVE: To identify fetal cord blood prognostic markers of symptomatic
      congenital human cytomegalovirus infection (HCMV). DESIGN: Retrospective
      observational study. SETTING: Fetal medicine unit in Milan and Medical virology
      unit in Pavia, Italy. POPULATION: HCMV-infected and -uninfected fetuses of
      mothers with primary HCMV infection during the period 1995-2009. METHODS:
      Overall, 94 blood samples from as many fetuses of 93 pregnant women experiencing
      primary HCMV infection were examined for multiple immunological, haematological
      and biochemical markers as well as virological markers. Congenital HCMV infection
      was diagnosed by detection of virus in amniotic fluid, and
      symptomatic/asymptomatic infections were determined by ultrasound scans, nuclear
      magnetic resonance imaging, histopathology or clinical examination at birth.
      Blood sample markers were retrospectively compared in symptomatic and
      asymptomatic fetuses with congenital infection. MAIN OUTCOME MEASURES: A
      statistical analysis was performed to determine the value of each parameter in
      predicting outcome. RESULTS: Univariate analysis showed that most nonviral and
      viral markers were significantly different in symptomatic (n = 16) compared with
      asymptomatic (n = 31) fetuses. Receiver operator characteristics analysis
      indicated that, with reference to an established cutoff for each marker, the best
      nonviral factors for differentiation of symptomatic from asymptomatic congenital
      infection were beta(2) -microglobulin and platelet count, and the best
      virological markers were immunoglobulin M antibody and DNAaemia. beta(2) 
      Microglobulin alone or the combination of these four markers reached the optimal
      diagnostic efficacy. CONCLUSIONS: The determination of multiple markers in fetal
      blood, following virus detection in amniotic fluid samples, is predictive of
      perinatal outcome in fetuses with HCMV infection.

PMID- 21199292
TI  - Effectiveness of nifedipine tocolysis to facilitate external cephalic version: a
      systematic review.
AB  - BACKGROUND: The success rates of external cephalic version (ECV) are improved
      with the use of betamimetic tocolytics, but these drugs are associated with
      maternal side effects. OBJECTIVES: To critically evaluate the effectiveness and
      advantages, if any, of nifedipine as a tocolytic for ECV. SEARCH STRATEGY: We
      searched PubMed, OVID [Medline, all evidence-based medicine (EBM) reviews],
      Embase, the Cochrane clinical trials register and references therein. SELECTION
      CRITERIA: Randomised trials comparing nifedipine with placebo or another
      tocolytic agent among women with a singleton, term breech or transverse
      presentation. DATA COLLECTION AND ANALYSIS: Two reviewers evaluated search
      results and extracted data from eligible studies using a standard data extraction
      form. Primary outcomes were success rates of ECV and cephalic presentation at
      delivery. Pooled relative risks and 95% confidence intervals were calculated for
      comparable studies, and where similar outcomes were assessed. MAIN RESULTS: Three
      trials met the inclusion criteria. Two trials (n = 176) compared nifedipine with
      terbutaline and found lower rates of successful ECV among women receiving
      nifedipine, pooled risk ratio = 0.67 (95% CI 0.48-0.93, P = 0.016). One trial (n
      = 320) comparing nifedipine with placebo did not find any significant difference
      in ECV success rates (41.6% nifedipine versus 37.2% placebo, P = 0.43). Although
      minor side effects were slightly higher with nifedipine compared with placebo,
      there was no significant difference in the rate of adverse maternal or neonatal
      outcomes or maternal satisfaction between the nifedipine and terbutaline groups,
      and women in both groups showed a similar preference for oral administration (62%
      nifedipine and 71% terbutaline). AUTHORS' CONCLUSIONS: This review found no
      evidence to support the use of nifedipine for tocolysis to facilitate external
      cephalic version.

PMID- 21199293
TI  - Head-to-body delivery interval and risk of fetal acidosis and hypoxic ischaemic
      encephalopathy in shoulder dystocia: a retrospective review.
AB  - OBJECTIVE: To examine the association between head-to-body delivery interval
      (HBDI) and cord arterial pH and base excess (BE), and the risk of development of
      hypoxic ischaemic encephalopathy (HIE). DESIGN: Retrospective review. SETTING: A
      university hospital. POPULATION: Pregnancies complicated with shoulder dystocia
      during the period 1995-2009. METHODS: Cases were identified from a search of the
      hospital electronic delivery records. Cord arterial pH and BE, and the incidence
      of HIE and perinatal death, were retrieved from medical records and correlated
      with HBDI, birth weight, mode of delivery and presence of nonreassuring fetal
      heart rate pattern and maternal diabetes using univariate analysis, followed by
      multivariate analysis. MAIN OUTCOME MEASURES: Any association between cord pH and
      HBDI. RESULTS: Of the 200 cases identified, the mean (standard deviation) HBDI
      was 2.5 minutes (1.5 minutes). Both HBDI and the presence of nonreassuring fetal
      heart rate pattern were independent factors for pH, and HBDI was the only
      significant factor for BE. Arterial pH dropped at a rate of 0.011 per minute [95%
      confidence interval (95% CI), 0.017-0.004; P = 0.002] with HBDI. The mode of
      delivery, birth weight and maternal diabetes did not affect blood gas levels. The
      respective risks of severe acidosis (pH < 7) and HIE with HBDI of <5 minutes were
      0.5% and 0.5% versus 5.9% and 23.5% with HBDI >= 5 minutes. CONCLUSIONS: Cord
      arterial pH drops with HBDI during shoulder dystocia, but the risk of acidosis or
      HIE is very low with HBDI < 5 minutes.

PMID- 21199294
TI  - CD4+ cell count and risk for antiretroviral drug resistance among women using
      peripartum nevirapine for perinatal HIV prevention.
AB  - OBJECTIVE: To determine the association between the antenatal CD4(+) cell count
      and the development of viral drug resistance following the use of peripartum
      nevirapine (NVP) for perinatal HIV prevention. DESIGN: Secondary analysis of data
      from a previously conducted randomised controlled trial. SETTING: Lusaka, Zambia.
      POPULATION: HIV-positive pregnant women. METHODS: We analysed the data from a
      clinical trial of single-dose tenofovir/emtricitabine (TDF/FTC) to reduce viral
      drug resistance associated with peripartum NVP. The trial population was
      categorised according to antenatal CD4(+) cell count (200-350, 351-500 and >500
      cells/MUl). MAIN OUTCOME MEASURES: The relative risk for acquiring drug
      resistance, determined by consensus sequencing and oligonucleotide ligation assay
      (OLA), was estimated using multivariable logistic regression. RESULTS: Of the 397
      study participants, 119 (30%) had a CD4(+) count of 200-350 cells/MUl, 135 (34%)
      had a CD4(+) count of 351-500 cells/MUl and 143 (36%) had a CD4(+) count of >500
      cells/MUl. Among women receiving no intervention, the risk for drug resistance
      appeared to increase as the CD4(+) cell count decreased. Participants with CD4(+)
      cell counts of 200-350 cells/MUl randomised to the study arm had the lowest risk,
      suggesting a higher efficacy of the intervention within this stratum. These
      results were consistent at 2 and 6 weeks, regardless of how drug resistance was
      measured. CONCLUSIONS: Women with CD4(+) cell counts of 200-350 cells/MUl may be
      at increased risk for viral drug resistance following the use of peripartum NVP.
      Given the high prevalence of NVP resistance and the clear benefits of treatment,
      antiretroviral therapy should be initiated among pregnant women with CD4(+) cell
      counts of <=350 cells/MUl.

PMID- 21199295
TI  - An unusual trigger for a neurogenic left ventricular dysfunction: Tako-Tsubo
      syndrome associated with hepatic encephalopathy.

PMID- 21199296
TI  - Clinical significance and potential of hepatic microRNA-122 expression in
      hepatitis C.
AB  - BACKGROUND AND AIMS: MicroRNAs are small non-coding RNA molecules that post
      transcriptionally regulate gene expression. Liver-specific microRNA-122 (miR-122)
      has been shown to facilitate the replication of hepatitis C virus (HCV) in human
      hepatoma cells in vitro. However, the clinical significance of hepatic miR-122 on
      HCV in human body is unclear. METHODS: Hepatic miR-122 expression was quantified
      using quantitative reverse-transcription polymerase chain reaction. We
      investigated the correlation between miR-122 expression and HCV load in liver
      samples from 185 patients seropositive for HCV antibody, including 151 patients
      seropositive for HCV RNA, and 31 patients seronegative for HCV RNA. RESULTS:
      Although hepatic miR-122 expression was weakly and positively correlated with the
      serum HCV load (rho=0.19, P<0.05), it was not correlated with the hepatic HCV
      load (rho=-0.14, P=0.08). The absence of a correlation between miR-122 expression
      and hepatic HCV load was also confirmed after stratification of histopathological
      liver damage (inflammatory activity grades and fibrosis stages). Furthermore,
      hepatic miR-122 expression in patients seronegative for HCV RNA was significantly
      higher than that in patients seropositive for HCV RNA (P<0.0001). The level of
      hepatic miR-122 expression was inversely correlated with the severity of
      functional and histopathological liver damage (P<0.0001), serum transaminase
      levels (P<0.0005). CONCLUSIONS: Compared with in vitro findings, hepatic miR-122
      expression is not correlated with HCV load in the human liver. Therefore, miR
      122, by itself, is not a critical molecular target for HCV therapy. MiR-122
      expression is inversely correlated with both functional and histopathological
      liver damage.

PMID- 21199297
TI  - The AMA in health care reform: a "Flexner Report" to improve pain medicine
      training and practice.

PMID- 21199298
TI  - Interesting findings in an initial clinical study of neuropeptides and pain.

PMID- 21199299
TI  - "Change and collaboration: the only way forward".

PMID- 21199300
TI  - International Spine Intervention Society 18(th) Annual Scientific Meeting, Maui
      HI.

PMID- 21199301
TI  - The First National Pain Medicine Summit--final summary report.
AB  - Pain is ubiquitous. At some point in time it affects everyone. For many millions
      pain becomes chronic, a scourge that impacts every facet of life-work, hobbies,
      family relations, social fabric, finances, happiness, mood, and even the very
      essence of identity. According to the National Institutes of Health (NIH), pain
      is one of our most important national public health problems, a silent epidemic.
      In 1998, NIH reported that the annual amount spent on health care, compensation,
      and litigation related to pain had reached one hundred billion dollars
      ($100,000,000,000). Considering that health care costs have doubled since then,
      it is not unreasonable to assume that the costs related to pain care have doubled
      as well. Millions of patients suffer needlessly with acute pain, with cancer
      pain, and with chronic pain. The ineffective management of pain results in an
      escalating cascade of health care issues. Acute pain that is not treated
      adequately and promptly results in persistent pain that eventually causes
      irreversible changes in the nervous system. This translates into progressive bio
      psycho-social epiphenomena resulting in further pain and disability. It creates a
      vicious cycle transforming a functional human being into an invalid who becomes a
      burden to family, to society, and to oneself. In the face of adequate medical
      science, adequate technical skills, and adequate resources the reality of delayed
      and inadequate pain care is paradoxical. This dilemma deserves close scrutiny and
      effective remediation. The American Medical Association (AMA), long dedicated to
      the need to improve pain care in this country, has been faced with this reality.
      It was from this vision that the idea of holding a Pain Medicine Summit was
      conceived. Resolution 321 (A-08) set in motion a process that would bring
      together a diverse group of stakeholders for the purpose of discussing the
      present and future status of pain care; a process that culminated in a broad
      based coalition of physicians and organizations dedicated to improving pain care,
      the first National Pain Medicine Summit. The process began with the adoption of
      Resolution 321 (A-08) at an AMA Annual House of Delegates meeting in June 2008.
      Resolution 321 (A-08) states, in part, that "...the AMA encourages relevant
      specialties to collaborate in studying: 1) the scope and practice and body of
      knowledge encompassed by the field of Pain Medicine; 2) the adequacy of
      undergraduate, graduate, and post graduate education in the principles and
      practices of the field of Pain Medicine, considering the current and anticipated
      medical need for the delivery of quality pain care; and 3) appropriate training
      and credentialing criteria for this multi-disciplinary field of medical
      practice." The next step was delegating the responsibility for implementing
      Resolution 321 (A-08) to the Pain and Palliative Medicine Specialty Section
      Council (PPMSSC). The PPMSSC, under the direction of its chairman, Philipp M.
      Lippe, MD, FACS, assumed responsibility in November 2008 for identifying a
      process that would achieve the goals established by Resolution 321 (A-08). The
      PPMSSC in turn established an Advisory Committee, charged with strategic
      planning, and an Implementation Committee, charged with tactical operations. The
      two groups began work immediately. The process included three distinct phases
      centered on a Pain Medicine Summit. Phase One involved a modified Delphi process
      identifying the five most pressing and relevant themes in pain care. Phase Two
      consisted of the Pain Medicine Summit itself, including a gathering of
      representatives from across the pain care spectrum to address the previously
      identified five most pressing themes. Phase Three was the preparation of this
      report, which describes the conclusions drawn and recommendations developed by
      the attendees at the Pain Medicine Summit. Based on a recommendation from the
      Advisory Committee, the PPMSSC decided to retain the services of a consulting
      firm to help the PPMSSC implement the Pain Medicine Summit process. In August
      2009, PPMSSC selected Grey Matters, a New York-based advisory firm. The PPMSSC
      also appointed a Steering Committee to assist Grey Matters and to coordinate all
      activities. The Committee consisted of Charles Brock, MD; Ronald Crossno, MD;
      Jose David, MD; Michel Dubois, MD; Albert Ray, MD; and Philipp M. Lippe, MD, FACS
      (chair). The consulting firm, Grey Matters, proposed a multi-phasic process in
      order to facilitate the implementation of the Pain Medicine Summit and to ensure
      a coordinated, efficient, and productive outcome. This process consisting of
      three phases-pre-summit, summit, and post-summit-is described in detail in the
      following section. All aspects of the project were closely coordinated and
      supervised by the Steering Committee, which included the selection of the team
      leaders of the five Workgroups, based on specific criteria. The Pain Medicine
      Summit, adhering to the dictates of Resolution 321 (A-08), explored the body of
      knowledge and the scope of practice of Pain Medicine; the education and training
      in medical school, graduate, and postgraduate programs; and the credentialing and
      certification processes in the field of Pain Medicine. It addressed the barriers
      hampering delivery of high quality pain care. It recognized the need for
      clarification and consensus in many areas. Several points of consensus emerged:
      The continuum of medical education in the field of Pain Medicine is inadequate
      and fragmented. It needs to be fortified in scope, content, and duration.
      Credentialing and certification processes in Pain Medicine are variable, diverse,
      and deficient in many instances. Deficiencies in these areas lead to suboptimal
      and fragmented pain care having a negative impact on direct patient care and
      public health. Effective and prompt remediation is desirable and essential to
      achieving the goal of high quality pain care. Barriers exist inhibiting or
      retarding progress toward the common good. There are several viable avenues to
      achieving our stated goal, "excellence in the delivery of high quality, cost
      effective pain care to the patients we serve," including the development of Pain
      Medicine as a distinct specialty with ACGME accredited residency programs and
      ABMS certification. The Pain Medicine Summit concluded with a number of
      recommendations, including the following: That the pain community remains engaged
      in addressing the issues raised and in mitigating the barriers. That the
      recommendations be referred to the AMA and the PPMSSC for support and
      implementation. That another national Pain Medicine Summit with enhanced
      participation be convened. That consideration be given to convening an
      International Pain Summit in conjunction with the IASP World Congress in
      Montreal.   That the final report of the Pain Medicine Summit be widely
      disseminated.

PMID- 21199302
TI  - Open-label study on the long-term efficacy, safety, and impact on quality of life
      of OROS hydromorphone ER in patients with chronic low back pain.
AB  - OBJECTIVE: To investigate the efficacy, safety, and impact on quality of life of
      long-term administration of OROS hydromorphone ER (8-128mg) in patients with
      chronic low back pain. DESIGN: A total of 113 adults with chronic low back pain
      who completed a 6-week open-label study were enrolled in this 6-month extension
      study. OUTCOME MEASURES: The primary end point was the daily pain relief rating
      obtained during monthly study visits. Secondary end points included Investigator
      and Patient Global Evaluations, Brief Pain Inventory scores obtained at monthly
      study visits, and quality-of-life measures (Medical Outcomes Study Questionnaire
      and 36-Item Short-Form Health Survey score) obtained at monthly intervals.
      RESULTS: Mean+/-SD change from baseline in pain relief with OROS hydromorphone ER
      for the Month 6 visit was 0.9+/-2.55 (P=0.0007) and for the last assessment of
      the extension study was 0.9+/-2.53 (P=0.0002). At the Month 6 visit, 81.3% of
      investigators and 71.0% of patients rated their satisfaction of pain relief with
      OROS hydromorphone ER treatment as good, very good, or excellent. Changes on the
      36-item Short Form Health Survey, a quality-of-life measure, were statistically
      significant for the physical composite scores for all extension phase time
      points, including Month 6 (2.1+/-5.34; P<0.0001) and the last assessment (2.4+/
      5.56; P<0.0001) and mental composite scores for all extension phase time points,
      including Month 6 (3.3+/-9.52; P=0.0006) and the last assessment (3.1+/-9.5;
      P=0.0008). Treatment with OROS hydromorphone ER also resulted in significant
      improvement in sleep disturbances. Adverse events included gastrointestinal and
      central nervous system symptoms. CONCLUSIONS: The results support the long-term
      use of OROS hydromorphone ER in managing chronic moderate to severe low back
      pain.

PMID- 21199303
TI  - Measurement of participant experience and satisfaction of exercise programs for
      low back pain: a structured literature review.
AB  - OBJECTIVES: The objective of this review was to identify measuring instruments
      that might be suitable for assessment of satisfaction and experience of exercise
      programs designed to help people with persistent, recurrent low back pain.
      DESIGN: The review was designed as a structured literature review adapted from
      the Cochrane Collaboration Systematic Review and the Quality of Reporting of Meta
      analyses and Preferred Reporting Items for Systematic Reviews and Meta-analyses
      Guidelines. METHODS: A priori inclusion and exclusion criteria were established
      and electronic databases were searched without limits until February 2009. Data
      extraction guidelines were developed to extract the same information from each
      included article. Thematic analysis, conducted by two independent reviewers, was
      applied to identify emergent codes and themes from the questionnaires. The
      relevant questions were then evaluated for applicability to the back pain
      population. RESULTS: Ten potentially useful instruments were described in the 11
      included articles. The following domains of experience were common to the
      included instruments: care-provider qualities, support staff, governance, access,
      and facilities. The answers to questions based on these themes may give valuable
      insights into the experience of exercise programs in general and for low back
      pain. CONCLUSIONS: Important information that would inform researchers and
      clinicians regarding the components of successful exercise programs may be gained
      from the development of an instrument that assesses experience of exercise
      program participation. Research into the experience of people who have
      participated in exercise programs may be a key to understanding their motivation,
      engagement, compliance or noncompliance and success or failure.

PMID- 21199305
TI  - Cancer pain: an age-based analysis.
AB  - OBJECTIVE: Although cancer pain (consistent and breakthrough pain [BTP; pain
      flares interrupting well-controlled baseline pain]) is common among cancer
      patients, its characteristics, etiology, and impact on health-related quality of
      life (HRQOL) across the lifespan are poorly understood. DESIGN: This longitudinal
      study examines age-based differences and pain-related interference in young and
      old patients with cancer-related pain over 6 months. Patients in the community
      with stage III or IV breast, prostate, colorectal, or lung cancer, or stage II-IV
      multiple myeloma with BTP completed surveys (upon initial assessment, 3 and 6
      months) assessing consistent pain, BTP, depressed affect, active coping ability,
      and HRQOL using previously validated measures. RESULTS: Respondents (N= 96) were
      70% white and 66% female, with a mean age of 57+/-10 years. There were no
      significant differences in pain severity based upon age. However, the younger
      group experienced more pain flares with greater frequency (P=0.05). The oldest
      group had better emotional functioning at baseline but worse physical functioning
      at 6 months. Younger groups also had worse cognitive functioning at 6 months
      (P=0.03). Pain interference was independent of age. CONCLUSIONS: These data
      provide evidence for the significant toll of cancer pain on overall health and
      well-being of young and old adults alike but demonstrate an increased toll for
      younger adults (especially financially). Beyond race and gender disparities,
      further health care disparities in the cancer and cancer pain were identified by
      age, illustrating the need for additional research across the lifespan in diverse
      cancer survivors.

PMID- 21199304
TI  - Acute pain management in hospitalized patients with cognitive impairment: a study
      of provider practices and treatment outcomes.
AB  - BACKGROUND: Despite new guidelines and nationally mandated regular assessments,
      managing pain in cognitively impaired patients remains a complex and challenging
      task. Numerous studies have focused on assessing pain in this population;
      however, studies of treatment are limited. PURPOSE: The purpose of this article
      was to characterize assessment and pain management strategies used by providers
      caring for hospitalized cognitively impaired patients with acute pain, and to
      assess for associations between amount of opioid received and specific adverse
      outcomes in this patient population. METHODS: Medical records of patients
      admitted to the Geriatrics Service or Orthopedic Service or evaluated by the
      Geriatrics Consult Service at an urban tertiary care hospital between September
      01, 2006 and September 30, 2007 with cognitive impairment and an acute pain
      problem on admission were reviewed. RESULTS: Participants (N=100) had a mean age
      of 86 years (range=68-99), and were mostly female (83%) with fracture-related
      pain (62%). A numeric pain score was recorded in 67% of nursing assessments vs
      <5% of physician assessments. Opioids were prescribed for 100% of the surgical
      patients vs 43% of the medical patients. Only 15% of patients were placed on a
      standing analgesic regimen. Nonpharmacological management was employed for 75% of
      surgical patients vs 43% of medical patients. Delirium occurred in 27% of
      patients, and 33% experienced an interruption of physical therapy. Neither,
      however, was associated with level of opioid use. CONCLUSIONS: Current assessment
      and treatment practices in acute pain management for cognitively impaired
      patients vary widely (to include service and provider type). Implementation of
      evidence-based guidelines is needed to improve patient care.

PMID- 21199306
TI  - A comparative study on the immediate effects of electroacupuncture at Sanyinjiao
      (SP6), Xuanzhong (GB39) and a non-meridian point, on menstrual pain and uterine
      arterial blood flow, in primary dysmenorrhea patients.
AB  - OBJECTIVE: The objective of this study was to compare the effects of Sanyinjiao
      (SP6), Xuanzhong (GB39), and an adjacent non-meridian point on menstrual pain and
      uterine arterial blood flow in primary dysmenorrhea patients. DESIGN: The design
      of the study was a prospective, randomized controlled trial. SETTING: The setting
      of the study was the Shandong Institute of Medical Imaging, Jinan, China.
      PATIENTS: The patients were 52 women with primary dysmenorrhea. INTERVENTIONS:
      Women received electroacupuncture (EA) at SP6 (n=13), GB39 (n=14), and an
      adjacent non-meridian point (n=12), respectively, for 10 minutes when scored >=40
      on a 100-mm visual analog scale (VAS), and for 30 minutes on the next 2 days.
      There was no EA in the waiting list group (n=13). OUTCOME MEASURES: Primary
      outcomes were menstrual pain, resistance index (RI), and the ratio between peak
      systolic to end-diastolic flow velocity (S/D) in uterine arteries. Secondary
      outcomes included verbal rating scale (VRS) and retrospective symptom scale
      (RSS). RESULTS: The SP6 group had a highly significant reduction in VAS scores
      compared with the waiting list group (-23.19mm, 95% confidence interval [CI]
      32.06 to -14.33, P<0.0001), GB39 group (-18.58mm, 95% CI -27.29 to -9.88,
      P<0.0001) and the non-meridian point group (-20.78mm, 95% CI -29.82 to -11.73,
      P<0.0001), respectively. A significant reduction in VRS scores was found in the
      SP6 group compared with the GB39 group (P=0.034) and the non-meridian point group
      (P=0.038). There were no significant differences of RI, S/D-values and RSS scores
      among the four groups (P>0.05). CONCLUSIONS: EA at SP6 can immediately relieve
      menstrual pain and minimize the influence of pain on daily life compared with
      GB39 and an adjacent non-meridian point. The data preliminarily show the
      specificity of SP6 for the immediate pain relief of primary dysmenorrhea.

PMID- 21199307
TI  - Nerve regeneration in neuropathic pain.

PMID- 21199309
TI  - Comparing partial and total tibial-nerve axotomy: long-term effects on prevalence
      and location of evoked pain behaviors.
AB  - Monophasic (one-time) nerve injuries heal without clinically significant residua
      in most cases, but rare individuals are left with neuropathic pain, even after
      seemingly minor lesions. The effects of lesion size on risk for chronic pain
      persistence are not well understood, particularly as concerns the complex
      regional pain syndrome, which is defined in part by pain "disproportionate" to
      the severity of the causative lesion, and extending outside the autonomous
      territory of a single nerve. To better clarify the expected prevalence of pain
      behaviors after nerve injury, we compared the effects in rats of different-sized
      axotomies on the prevalence and location of evoked pain behaviors. To highlight
      clinical relevance, we also describe a patient with iatrogenic tibial-nerve
      injury causing similar chronic neuralgia. Adult male Sprague-Dawley rats were
      anesthetized and had either 1/3, 2/3 or their entire left tibial nerves tightly
      ligated at two sites just below the sciatic trifurcation and the interposed nerve
      was cut. Unoperated rats provided controls. Sensory function in the tibial and
      sural-innervated territories of both plantar hindpaws was assessed for as long as
      6 months postoperatively. Soon after surgery, evoked pain behavior developed in
      the ipsilesional sural-innervated site in a subset of axotomized rats and
      recovery was variable. The relationship between lesion size and prevalence and
      severity of hyperalgesia varied for different pain behaviors, with pinprick
      hyperalgesia clearly more likely after larger axotomies. In summary, partial
      tibial-nerve injury in rats models human disease and suggests that expectations
      of proportionality between lesion size and development of neuropathic pain may
      need revision.

PMID- 21199310
TI  - Effect of pregabalin in the treatment of refractory neck pain: cost and clinical
      evidence from medical practice in orthopedic surgery and rehabilitation clinics.
AB  - BACKGROUND: The study aims to prospectively analyze the effect of adding
      pregabalin upon costs and consequences in the treatment of refractory neck pain
      under routine medical practice. METHODS: A secondary analysis was carried out
      including patients over 18 years, with 6-month chronic neck pain refractory from
      a prospective, naturalistic, 12-week two-visit study. The analysis compared
      patients adding pregabalin to its therapy vs. usual care. Severity of pain,
      healthcare resources utilization, lost workday equivalents (LWDE) because of
      pain, and related cost-adjusted reductions were assessed. RESULTS: A total of 312
      patients (65.3% women, age 54.2 [12.1] years), 78.2% receiving pregabalin, were
      analyzed. Adding pregabalin was associated with higher adjusted reduction in pain
      severity: -3.2 (1.8) points, 55.4% responders (>=50% baseline pain reduction) vs.
      -2.3 (2.0) and 38.2%, respectively; P<0.001, yielding a higher reduction in mean
      LWDE: 20.1 (23.1) vs. 8.2 (22.4); P=0.014, which produced significant reductions
      in the indirect components of cost: ?1,041.0 (1,222.8) vs. ?457.3 (1,132.1),
      P=0.028. The costs of pregabalin (?309.8 [193.2] vs. ?26.4 [79.6], P<0.001) was
      offset by higher numerical reductions in the other components of costs, producing
      similar direct cost reductions in both groups at the end of the study: ?66.8
      (1,080.8) and ?143.5 (1,922.4), respectively; P=0.295. CONCLUSION: Compared with
      usual care, the addition of pregabalin to treat refractory neck pain seems to be
      associated with a higher reduction in pain severity and lost work-days
      equivalents, which in turn results in a greater reduction of the indirect
      components of cost while maintaining similar healthcare cost levels despite its
      higher price.

PMID- 21199311
TI  - Medication adherence and healthcare costs among fibromyalgia patients treated
      with duloxetine.
AB  - OBJECTIVE: The study aims to examine predictors associated with duloxetine
      adherence and its association with healthcare costs among fibromyalgia patients.
      METHODS: Administrative claims from both commercially and Medicare supplemental
      insured fibromyalgia patents aged 18+ who initiated duloxetine in 2006 were
      analyzed. Initiation was defined as a 90-day clean period without duloxetine. The
      dispense date of the first duloxetine prescription was denoted as the index date.
      Two cohorts were constructed based on duloxetine adherence over the 12-month
      postindex period (high adherence as medication possession ratio >=0.8).
      Predictors of high adherence were examined via logistic regression. Generalized
      linear regressions were performed to estimate the association between duloxetine
      adherence and healthcare costs. RESULTS: A total of 4,869 commercially and 566
      Medicare supplemental-insured fibromyalgia patients were identified. Two-thirds
      of patients had low adherence. Higher duloxetine average daily dose (ADD) was
      associated with increased adherence (reference group=30mg; Commercial: Odds ratio
      [OR]=3.03, 2.40, and 3.73 for 31 to 59mg, 60mg, and >60mg, respectively, all
      P<0.05; Medicare supplemental: OR=3.11, 2.33, and 4.76 for 31 to 59mg, 60mg, and
      >60mg, respectively, all P<0.05). Commercially insured patients with high
      adherence had significantly lower total healthcare costs than low-adherence
      patients (-$1,164, P<0.05), primarily because of lower inpatient (-$2,222,
      P<0.05) and outpatient (-$1,075, P<0.05) costs. Medicare supplemental-insured
      patients with high adherence had similar overall and inpatient costs, but
      significantly lower outpatient costs (-$2,025, P<0.05). CONCLUSION: Fibromyalgia
      patients with higher duloxetine ADD were more likely to adhere to the therapy.
      High duloxetine adherence was associated with lower (Commercial) or similar
      (Medicare supplemental) healthcare costs.

PMID- 21199312
TI  - Herpes zoster pain, postherpetic neuralgia, and quality of life in the elderly.
AB  - Herpes zoster pain and postherpetic neuralgia (PHN) particularly affect older
      persons. This literature review presents how quality of life is evaluated and the
      consequences of shingles and PHN on the quality of life of older persons.
      Although more than 150 articles have been published on herpes zoster and its
      consequences, specific studies focusing on the older population are needed, in
      several domains like epidemiology, preventive medicine, neuropsychology, and
      pharmacology.

PMID- 21199313
TI  - Anesthesiologists' views on using immune modulating drugs in pain medicine.
AB  - With few exceptions, anesthesiologists have not received training in the use of
      immune modulating drugs (IMDs); but recent evidence suggests that such drugs may
      be effective in reducing chronic pain. We therefore wished to learn how
      anesthesiologists working in pain medicine might envisage the treatment of their
      patients with IMDs in the future. We expected that anesthesiologists would want
      to refer patients for treatment with IMDs to medical colleagues, such as
      oncologists or rheumatologists, with prior experience in using these drugs,
      rather than treat these patients within their own practice. We conducted
      questionnaire surveys among anesthesiologists working in pain medicine in both
      the Netherlands and the U.K. to explore their views on using IMDs. Contrary to
      what we had expected, we found that a majority of the respondents would
      administer IMDs within their own practice, after appropriate training. The
      overall response rates were 30% and 23%, respectively; therefore, no firm
      conclusions can be drawn as to the views of the majority of practicing pain
      specialists. Our findings may have implications for the planning of both health
      service delivery and training in pain medicine.

PMID- 21199314
TI  - Transdermal buprenorphine for central neuropathic pain: clinical reports.
AB  - Transdermal buprenorphine is an effective analgesic for a variety of pain
      conditions. Traditionally, neuropathic pain is treated with medications such as
      tricyclic antidepressants or anticonvulsants, with opioid medications as second
      or third-line agents. We present two different painful conditions of presumed
      neuropathic origin, with complex etiopathogenesis, which were successfully
      treated with buprenorphine. The results of treatment of these neuropathic pain
      syndromes with buprenorphine are encouraging, suggesting that it might represent
      a valid alternative to standard approaches for central neuropathic pain.

PMID- 21199315
TI  - Evidence-based interventional pain medicine according to clinical diagnoses. 18.
      Painful diabetic polyneuropathy.
AB  - In the industrialized world, polyneuropathy induced by diabetes mellitus (DM) is
      one of the most prevalent forms of neuropathy. Diabetic neuropathy can result
      from a direct toxic effect of glucose on nerve cells. Additionally, the damage of
      the nerve structures (central and peripheral) is accompanied by a microvascular
      dysfunction, which damages the vasa nervorum. More than 80% of the patients with
      DM-induced polyneuropathy have a distal and symmetric presentation. The initial
      symptoms are: signs of diminished sensation, burning feet, which may occur
      particularly during the night and worsen when touched, and tingling sensation in
      the feet. Attacks of shooting pain may also occur. Proper control of DM is
      mandatory. Based on the recently published National Institute for Health and
      Clinical Excellence guidelines, treatment of painful diabetic neuropathy should
      start with duloxetine or amitriptyline if duloxetine is contraindicated. If pain
      relief is inadequate, monotherapy with amitriptyline or pregabalin, or
      combination therapy with amitriptyline and pregabalin should be considered. If
      pain relief is still insufficient, tramadol instead of or in combination with a
      second-line agent should be considered. In patients who are unable to take oral
      medication, topical lidocaine can be considered for localized pain. There are
      currently four studies showing that spinal cord stimulation can potentially
      provide pain alleviation for the longer term in patients with painful diabetic
      polyneuropathy. Complications are mainly implant related, though infections also
      occur. The available evidence (2 C+) justifies spinal cord stimulation to be
      considered, preferably study related.

PMID- 21199316
TI  - Are psychoactive substance (opioid)-dependent chronic pain patients hyperalgesic?
AB  - OBJECTIVES: One indirect line of evidence for opioid-induced hyperalgesia (OIH)
      in humans is decreased pain thresholds (PTREs) and tolerances (PTOLs) in opioid
      addicts on opioids. There are a number of such studies in opioid maintained
      addicts, but no such studies in chronic pain patients (CPPs) with current opioid
      addiction. The objective of this study was to determine if this group
      demonstrates hyperalgesia. METHODS: CPPs were subdivided into those with
      psychoactive substance (opioid dependence) (PSOD) (n=38) (addicted) and those
      taking opioids but without PSOD (n=198) (not addicted). A group of opioid-free
      non-CPPs served as a control group (n=36). PTREs/PTOLs were determined in each
      group by pressure pain stimulation in both the right and left index fingers.
      PTREs/PTOLs were compared by analysis of variance among the three groups
      controlling for sex/age and by analysis of covariance between the PSOD CPPs and
      non-PSOD CPPs controlling for duration of pain and visual analog scale pain level
      over the last 24 hours. RESULTS: The PSOD and non-PSOD CPPs had significantly
      lower PTREs and PTOLs vs. the control group, ie, were hyperalgesic. However, they
      were not significantly different from each other. CONCLUSIONS: This study
      contributes to the human OIH literature. However, because of the potential
      confounders in this study, the issue of OIH in humans remains unresolved.

PMID- 21199317
TI  - Exposure to potential CYP450 pharmacokinetic drug-drug interactions among
      osteoarthritis patients: incremental risk of multiple prescriptions.
AB  - Patients taking more than one drug metabolized through the cytochrome P450
      (CYP450) enzyme system experience a drug-drug exposure (DDE), which puts them at
      risk for a potential pharmacokinetic drug-drug interaction (DDI), defined as two
      or more drugs interacting in such a way that the effectiveness and/or toxicity of
      one or all drugs are changed. Any patient subjected to a DDE is at risk for a
      potentially serious DDI, the epidemiology of which has not been thoroughly
      studied. Many drugs are metabolized primarily via the CYP450 enzyme system,
      including certain opioids used to manage moderate to severe chronic pain. We
      conducted a retrospective analysis of a large commercial claims database and a
      Medicare database to assess the prevalence of DDEs among patients with
      osteoarthritis taking CYP450-metabolized opioids. The overall prevalence of DDEs
      in this population was 26%, with females more likely to experience DDEs than
      males (28.4% vs. 21.0%, respectively). The number of unique concurrent
      prescriptions at baseline, gender, age, and Charlson Comorbidity Index were
      statistically significant predictors of DDEs (P < 0.05). This study challenged
      previous assumptions about DDEs in that advanced age was not positively
      associated with the risk of DDE. However, the number of prescriptions the patient
      received in the 90-day window prior to the index date was a risk factor. For
      patients taking at least two medications in the 90-day period prior to the index
      date, every additional prescription taken increased their risk for a DDE during
      the observation period by 138% (on average). The risk of DDE during the study
      period was threefold greater for patients with one medication in the 90-day
      period before index date compared with similar patients with no prescriptions in
      that same period before the index date. DDEs are more common than may be
      generally believed in patients with osteoarthritis, regardless of age, and can
      occur even in patients taking few medications. When selecting an opioid analgesic
      to treat osteoarthritis, physicians should consider the potential for exposure of
      these patients to drugs that could interact unfavorably. 

PMID- 21199318
TI  - Percutaneous sacroplasty and sacroiliac joint cementation under fluoroscopic
      guidance for lower back pain related to sacral metastatic tumors with sacroiliac
      joint invasion.
AB  - Cancer patients with bone metastases are at risk of a variety of skeletal events,
      including vertebral compression and pathologic fractures. Approximately 30% to
      40% of patients with advanced lung cancer will develop bone metastases in the
      course of their disease, resulting in a significant negative impact on both
      morbidity and survival. Skeletal complications of bone metastases include pain,
      pathologic fractures, spinal cord compression, and hypercalcemia. The spine is
      the most frequent site of skeletal metastases. We present a 48-year-old female
      with intractable and incapacitating low back pain because of metastatic bone
      tumor in the left lateral side of S1 and S2 with left sacroiliac invasion.
      Imaging identified a metastatic invasion of the sacrum. Percutaneous sacroplasty,
      a safe and effective procedure for sacral-insufficient fractures, was performed
      under fluoroscopy guidance. However, the expected pain relief was not achieved.
      At 1 month, the patient remained invalided by severe back pain, which was
      localized to the left sacroiliac joint. In a second procedure, the sacroiliac
      joint was cemented. Pain relief was complete, immediate, and sustained until the
      patient's death related to the underlying oncologic disease. No complications
      were observed. Few reports exist about the treatment of sacral metastatic tumors
      with percutaneous sacroplasty. Further, no previous reports about sacroiliac
      joint cementation for joint stabilization have been found. In the present case,
      sacroiliac joint cementation successfully resolved residual pain that remained
      despite percutaneous sacroplasty treatment of the pathologic sacral fracture.

PMID- 21199320
TI  - A meta-analysis of pain response in the treatment of fibromyalgia.
AB  - OBJECTIVE: This meta-analysis compared efficacy (pain response) of drugs that are
      licensed or commonly used in the treatment of fibromyalgia. A meta-analysis of
      safety measured via discontinuation because of adverse events was also performed.
      METHODS: We conducted a meta-analysis of 21 clinical trials to estimate treatment
      differences vs. placebo, separately, for duloxetine, fluoxetine, gabapentin,
      milnacipran, pramipexole, pregabalin, either of two tricyclic antidepressants,
      and tramadol plus paracetamol. Indirect treatment comparisons using mixed
      treatment comparisons methodology were conducted for all pairwise comparisons.
      Pain response was analyzed as improvement of at least 30%, and separately of 50%,
      from baseline. RESULTS: When compared with placebo, statistically significant
      pain responses (improvement of 30% and 50%) were observed for patients treated
      with duloxetine, milnacipran 200 mg/day, pregabalin 300 or 450 mg/day, and
      tramadol plus paracetamol. Treatment with fluoxetine, gabapentin, or milnacipran
      100 mg/day resulted in significant findings for the 30% improvement in pain
      response. The meta-analysis showed a statistically increased risk of
      discontinuation because of adverse events for milnacipran 100 and 200 mg/day
      (both P < 0.001), and pregabalin 300 and 450 mg/day (P = 0.009 and P < 0.001,
      respectively). All other treatments, except fluoxetine, showed numerically
      increased risk over placebo for discontinuation because of adverse events. In the
      indirect comparisons, no pairwise comparison of active treatments reached
      statistical significance for either pain response end point. CONCLUSION: All
      eight active treatments displayed evidence suggesting improvement over placebo in
      the treatment of pain in patients suffering from fibromyalgia. Indirect
      comparison of active treatments found no strong differences.

PMID- 21199319
TI  - Real-world evaluation of health-care resource utilization and costs in employees
      with fibromyalgia treated with pregabalin or duloxetine.
AB  - OBJECTIVE: To evaluate changes in health-care resource use and costs after
      initiating pregabalin or duloxetine in employees with fibromyalgia (FM). METHODS:
      Employees (18 to 64 years old) with at least one claim for an FM-attributable
      medication within 60 days following an FM diagnosis were identified using the
      Thomson Reuters MarketScan((r)) Commercial Database (2006 to 2008). Patients
      newly initiated on pregabalin were propensity score matched to patients newly
      initiated on duloxetine. These treatment cohorts were evaluated for changes
      between the 6-month pre- and post-initiation periods in health-care utilization
      including prescriptions, imputed medically related work loss and expenditures.
      Pre- to post-initiation changes were compared between pregabalin and duloxetine
      using a difference-in-difference approach based on univariate statistics and
      multivariable models. RESULTS: A total of 731 employees with FM initiated on
      pregabalin (89.9% female, mean age 47.1+/-9.7 years) were matched with 731
      employees initiated on duloxetine (89.5% female, mean age 47.1+/-9.8 years);
      other demographic and clinical characteristics were also comparable between
      cohorts. The adjusted marginal effects were not statistically significant for pre
      to post-changes in opioid utilization (P=0.856), number of FM-attributable
      (P=0.151) or FM-related medications (P=0.462), and all-cause (P=0.323) or FM
      attributable (P=0.991) expenditures. Pregabalin was associated with a
      significantly lower probability of any medically related work loss of 3.2
      percentage points (P=0.030) compared with duloxetine, but changes in indirect
      costs were not significantly different (P=0.600). CONCLUSIONS: The changes in
      health resource utilization and costs after initiation of pregabalin were not
      significantly different than the changes observed after initiation of duloxetine.
      These results not only demonstrate an overall similarity of resource utilization,
      but also suggest cost neutrality between pregabalin and duloxetine.

PMID- 21199321
TI  - More on: adenosine diphosphate-inducible platelet reactivity shows a pronounced
      age dependency in the initial phase of antiplatelet therapy with clopidogrel.

PMID- 21199322
TI  - The anticancer flavonoid chrysin induces the unfolded protein response in
      hepatoma cells.
AB  - Chrysin is a natural and biologically active flavonoid with anticancer effects.
      However, little is known about the adaptive response of cancer cells to chrysin.
      Chrysin reportedly has proteasome inhibitor activity. Previous studies
      demonstrated that proteasome inhibitors might induce endoplasmic reticulum (ER)
      stress response. In this study, we aimed to determine the effects of chrysin on
      hepatoma cells and roles of the ER-resident protein GRP78 (glucose-regulated
      protein 78) in its action. Also, we investigated the effects of green tea
      polyphenol (-)-epigallocatechin-3-gallate (EGCG), a natural GRP78 inhibitor, on
      the sensitivity of hepatoma cells to chrysin. Here, we report that chrysin
      inhibits hepatoma cells growth and induces apoptosis in a dose-dependent manner.
      Chrysin induces GRP78 overexpression, X-box binding protein-1 splicing and
      eukaryotic initiation factor 2alpha phosphorylation, hallmarks of the unfolded
      protein response. GRP78 knockdown potentiates chrysin-induced caspase-7 cleavage
      in hepatoma cells and enhances chrysin-induced apoptosis. EGCG overcomes chrysin
      induced GRP78 expression. Combination of EGCG potentiates chrysin-induced caspase
      7 and poly (ADP-ribose) polymerase (PARP) cleavage. Finally, EGCG sensitizes
      hepatoma cells to chrysin through caspase-mediated apoptosis. These data suggest
      that chrysin triggers the unfolded protein response. Abrogation of GRP78
      induction may improve the anticancer effects of chrysin. Combination of EGCG and
      chrysin represents a new regimen for cancer chemoprevention and therapeutics.

PMID- 21199323
TI  - Contribution of vascular cell-derived cytokines to innate and inflammatory
      pathways in atherogenesis.
AB  - Inflammation is a central element of atherogenesis. Innate pathways contribute to
      vascular inflammation. However, the initial molecular process(es) starting
      atherogenesis remain elusive. The various risk factors, represented by particular
      compounds (activators), may cause altered cellular functions in the endothelium
      (e.g. vascular endothelial cell activation or -dysfunction), in invading cells
      (e.g. inflammatory mediator production) or in local vessel wall cells (e.g.
      inflammatory mediators, migration), thereby triggering the innate inflammatory
      process. The cellular components of innate immunology include granulocytes,
      natural killer cells and monocytes. Among the molecular innate constituents are
      innate molecules, such as the toll-like receptors or innate cytokines.
      Interleukin-1 (IL-1) and IL-6 are among the innate cytokines. Cytokines are
      potent activators of a great number of cellular functions relevant to maintain or
      commove homeostasis of the vessel wall. Within the vessel wall, vascular smooth
      muscle cells (SMCs) can significantly contribute to the cytokine-dependent
      inflammatory network by: (i) production of cytokines, (ii) response to cytokines
      and (iii) cytokine-mediated interaction with invading leucocytes. The cytokines
      IL-1 and IL-6 are involved in SMC-leucocyte interaction. The IL-6 effects are
      proposed to be mediated by trans-signalling. Dysregulated cellular functions
      resulting from dysregulated cytokine production may be the cause of cell
      accumulation, subsequent low-density lipoprotein accumulation and deposition of
      extracellular matrix (ECM). The deposition of ECM, increased accumulation of
      leucocytes and altered levels of inflammatory mediators may constitute an 'innate
      immunovascular-memory' resulting in an ever-growing response to anew invasion.
      Thus, SMC-fostered inflammation, promoted by invading innate cells, may be a
      potent component for development and acceleration of atherosclerosis.

PMID- 21199324
TI  - Caveolin-1 is required for contractile phenotype expression by airway smooth
      muscle cells.
AB  - Airway smooth muscle cells exhibit phenotype plasticity that underpins their
      ability to contribute both to acute bronchospasm and to the features of airway
      remodelling in chronic asthma. A feature of mature, contractile smooth muscle
      cells is the presence of abundant caveolae, plasma membrane invaginations that
      develop from the association of lipid rafts with caveolin-1, but the functional
      role of caveolae and caveolin-1 in smooth muscle phenotype plasticity is unknown.
      Here, we report a key role for caveolin-1 in promoting phenotype maturation of
      differentiated airway smooth muscle induced by transforming growth factor (TGF)
      beta(1). As assessed by Western analysis and laser scanning cytometry, caveolin-1
      protein expression was selectively enriched in contractile phenotype airway
      myocytes. Treatment with TGF-beta(1) induced profound increases in the
      contractile phenotype markers sm-alpha-actin and calponin in cells that also
      accumulated abundant caveolin-1; however, siRNA or shRNAi inhibition of caveolin
      1 expression largely prevented the induction of these contractile phenotype
      marker proteins by TGF-beta(1). The failure by TGF-beta(1) to adequately induce
      the expression of these smooth muscle specific proteins was accompanied by a
      strongly impaired induction of eukaryotic initiation factor-4E binding protein(4E
      BP)1 phosphorylation with caveolin-1 knockdown, indicating that caveolin-1
      expression promotes TGF-beta(1) signalling associated with myocyte maturation and
      hypertrophy. Furthermore, we observed increased expression of caveolin-1 within
      the airway smooth muscle bundle of guinea pigs repeatedly challenged with
      allergen, which was associated with increased contractile protein expression,
      thus providing in vivo evidence linking caveolin-1 expression with accumulation
      of contractile phenotype myocytes. Collectively, we identify a new function for
      caveolin-1 in controlling smooth muscle phenotype; this mechanism could
      contribute to allergic asthma.

PMID- 21199325
TI  - Endothelial progenitor cells are integrated in newly formed capillaries and alter
      adjacent fibrovascular tissue after subcutaneous implantation in a fibrin matrix.
AB  - Vascularization of bioartificial matrices is crucial for successful tissue
      engineering. Endothelial progenitor cells (EPC) have shown vascularization
      potential in ischemic conditions and may also support blood vessel formation in
      tissue-engineered matrices. The aim of our study was to investigate the impact of
      a well-characterized murine embryonal EPC line (T17b-EPC) on vascularization and
      fibrovascular granulation tissue formation after suspension in a fibrine matrix
      followed by subcutaneous implantation in a separation chamber in rats. EPC were
      fluorescently labelled in vitro prior to implantation. After 3, 7 or 14 days,
      animals were killed followed by explantation and histological analysis of the
      constructs. Before the end of the experiment, Bandeirea Simplicifolia lectin was
      intravenously injected to mark the vascular ingrowth into the implanted
      constructs. The transplanted cells were histologically detected at all time
      points and located almost exclusively within the fibrin matrix at day 3 but the
      number of cells in the clot continuously decreased over day 7 to day 14.
      Conversely, cells were detected within the newly formed granulation tissue in
      increasing numbers from day 3 over day 7 to day 14. Transplanted cells were also
      found in the intermuscular septa. Cell viability was confirmed by use of an EPC
      clone expressing beta-galactosidase. Fluorescence microscopy demonstrated
      integration of the transplanted cells in newly formed blood vessels within the
      fibrovascular granulation tissue adjacent to the fibrin clot. Presence of cells
      in the fibrin clot lead to thicker granulation tissue and an increased blood
      vessel diameter compared to cell-free controls. Organ standard controls showed
      presence of the transplanted cells in spleens at day 14 after transplantation. In
      summary, EPC exhibited biological activity after subcutaneous implantation in a
      fibrin matrix by migration from the fibrin clot into the granulation tissue and
      along intermuscular septae, undergoing differentiation into mature endothelial
      cells and integration into newly formed blood vessels and altering fibrovascular
      granulation tissue development. EPC may hold promise to modulate blood vessel
      formation in bioartificial matrices.

PMID- 21199326
TI  - P60TRP interferes with the GPCR/secretase pathway to mediate neuronal survival
      and synaptogenesis.
AB  - In the present study, we show that overexpression of the G-protein-coupled
      receptor (GPCR)-associated sorting protein p60TRP (transcription regulator
      protein) in neural stem cells (NSCs) and in a transgenic mouse model modulates
      the phosphorylation and proteolytic processing of amyloid precursor protein
      (App), N-cadherin (Cdh2), presenilin (Psen) and tau protein (Mapt). Our results
      suggest that p60TRP is an inhibitor of Bace1 (beta-site App cleaving enzyme) and
      Psen. We performed several apoptosis assays [Annexin-V, TdT-mediated dUTP Nick
      End Labeling (TUNEL), caspase-3/7] using NSCs and PC12 cells (overexpressing
      p60TRP and knockdown of p60TRP) to substantiate the neuroprotective role of
      p60TRP. Functional analyses, both in vitro and in vivo, revealed that p60TRP
      promotes neurosynaptogenesis. Characterization of the cognitive function of
      p60TRP transgenic mice using the radial arm water maze test demonstrated that
      p60TRP improved memory and learning abilities. The improved cognitive functions
      could be attributed to increased synaptic connections and plasticity, which was
      confirmed by the modulation of the gamma-aminobutyric acid receptor system and
      the elevated expression of microtubule-associated protein 2, synaptophysin and
      Slc17a7 (vesicle glutamate transporter, Vglut1), as well as by the inhibition of
      Cdh2 cleavage. In conclusion, interference with the p60TRP/ GPCR/secretase
      signalling pathway might be a new therapeutic target for the treatment of
      Alzheimer's disease (AD).

PMID- 21199327
TI  - Interplay between Ca2+ cycling and mitochondrial permeability transition pores
      promotes reperfusion-induced injury of cardiac myocytes.
AB  - Uncontrolled release of Ca(2+) from the sarcoplasmic reticulum (SR) contributes
      to the reperfusion-induced cardiomyocyte injury, e.g. hypercontracture and
      necrosis. To find out the underlying cellular mechanisms of this phenomenon, we
      investigated whether the opening of mitochondrial permeability transition pores
      (MPTP), resulting in ATP depletion and reactive oxygen species (ROS) formation,
      may be involved. For this purpose, isolated cardiac myocytes from adult rats were
      subjected to simulated ischemia and reperfusion. MPTP opening was detected by
      calcein release and by monitoring the DeltaPsi(m). Fura-2 was used to monitor
      cytosolic [Ca(2+)](i) or mitochondrial calcium [Ca(2+)](m), after quenching the
      cytosolic compartment with MnCl(2). Mitochondrial ROS [ROS](m) production was
      detected with MitoSOX Red and mag-fura-2 was used to monitor Mg(2+)
      concentration, which reflects changes in cellular ATP. Necrosis was determined by
      propidium iodide staining. Reperfusion led to a calcein release from
      mitochondria, DeltaPsi(m) collapse and disturbance of ATP recovery.
      Simultaneously, Ca(2+) oscillations occurred, [Ca(2+)](m) and [ROS](m) increased,
      cells developed hypercontracture and underwent necrosis. Inhibition of the SR
      driven Ca(2+) cycling with thapsigargine or ryanodine prevented mitochondrial
      dysfunction, ROS formation and MPTP opening. Suppression of the mitochondrial
      Ca(2+) uptake (Ru360) or MPTP (cyclosporine A) significantly attenuated Ca(2+)
      cycling, hypercontracture and necrosis. ROS scavengers (2-mercaptopropionyl
      glycine or N-acetylcysteine) had no effect on these parameters, but reduced
      [ROS](m). In conclusion, MPTP opening occurs early during reperfusion and is due
      to the Ca(2+) oscillations originating primarily from the SR and supported by
      MPTP. The interplay between Ca(2+) cycling and MPTP promotes the reperfusion
      induced cardiomyocyte hypercontracture and necrosis. Mitochondrial ROS formation
      is a result rather than a cause of MPTP opening.

PMID- 21199328
TI  - Effects of S1P on skeletal muscle repair/regeneration during eccentric
      contraction.
AB  - Skeletal muscle regeneration is severely compromised in the case of extended
      damage. The current challenge is to find factors capable of limiting muscle
      degeneration and/or potentiating the inherent regenerative program mediated by a
      specific type of myoblastic cells, the satellite cells. Recent studies from our
      groups and others have shown that the bioactive lipid, sphingosine 1-phosphate
      (S1P), promotes myoblast differentiation and exerts a trophic action on
      denervated skeletal muscle fibres. In the present study, we examined the effects
      of S1P on eccentric contraction (EC)-injured extensor digitorum longus muscle
      fibres and resident satellite cells. After EC, skeletal muscle showed evidence of
      structural and biochemical damage along with significant electrophysiological
      changes, i.e. reduced plasma membrane resistance and resting membrane potential
      and altered Na(+)  and Ca(2+)  current amplitude and kinetics. Treatment with
      exogenous S1P attenuated the EC-induced tissue damage, protecting skeletal muscle
      fibre from apoptosis, preserving satellite cell viability and affecting
      extracellular matrix remodelling, through the up-regulation of matrix
      metalloproteinase 9 (MMP-9) expression. S1P also promoted satellite cell renewal
      and differentiation in the damaged muscle. Notably, EC was associated with the
      activation of sphingosine kinase 1 (SphK1) and with increased endogenous S1P
      synthesis, further stressing the relevance of S1P in skeletal muscle protection
      and repair/regeneration. In line with this, the treatment with a selective SphK1
      inhibitor during EC, caused an exacerbation of the muscle damage and attenuated
      MMP-9 expression. Together, these findings are in favour for a role of S1P in
      skeletal muscle healing and offer new clues for the identification of novel
      therapeutic approaches to counteract skeletal muscle damage and disease.

PMID- 21199330
TI  - Methyl deficient diet aggravates experimental colitis in rats.
AB  - Inflammatory bowel diseases (IBD) result from complex interactions between
      environmental and genetic factors. Low blood levels of vitamin B12 and folate and
      genetic variants of related target enzymes are associated with IBD risk, in
      population studies. To investigate the underlying mechanisms, we evaluated the
      effects of a methyl-deficient diet (MDD, folate, vitamin B12 and choline) in an
      experimental model of colitis induced by dextran sodium sulphate (DSS), in rat
      pups from dams subjected to the MDD during gestation and lactation. Four groups
      were considered (n = 12-16 per group): C DSS(-) (control/DSS(-)), D DSS(-)
      (deficient/DSS(-)), C DSS(+) (control/DSS(+)) and D DSS(+) (deficient/DSS(+)).
      Changes in apoptosis, oxidant stress and pro-inflammatory pathways were studied
      within colonic mucosa. In rat pups, the MDD produced a decreased plasma
      concentration of vitamin B12 and folate and an increased homocysteine (7.8 +/-
      0.9 versus 22.6 +/- 1.2 MUmol/l, P < 0.001). The DSS-induced colitis was
      dramatically more severe in the D DSS(+) group compared with each other group,
      with no change in superoxide dismutase and glutathione peroxidase activity, but
      decreased expression of caspase-3 and Bax, and increased Bcl-2 levels. The mRNA
      levels of tumour necrosis factor (TNF)-alpha and protein levels of p38, cytosolic
      phospolipase A2 and cyclooxygenase 2 were significantly increased in the D DSS(+)
      pups and were accompanied by a decrease in the protein level of tissue inhibitor
      of metalloproteinases (TIMP)3, a negative regulator of TNF-alpha. MDD may cause
      an overexpression of pro-inflammatory pathways, indicating an aggravating effect
      of folate and/or vitamin B12 deficiency in experimental IBD. These findings
      suggest paying attention to vitamin B12 and folate deficits, frequently reported
      in IBD patients.

PMID- 21199329
TI  - Future dentistry: cell therapy meets tooth and periodontal repair and
      regeneration.
AB  - Cell-based tissue repair of the tooth and - tooth-supporting - periodontal
      ligament (PDL) is a new attractive approach that complements traditional
      restorative or surgical techniques for replacement of injured or pathologically
      damaged tissues. In such therapeutic approaches, stem cells and/or progenitor
      cells are manipulated in vitro and administered to patients as living and dynamic
      biological agents. In this review, we discuss the clonogenic potential of human
      dental and periodontal tissues such as the dental pulp and the PDL and their
      potential for tooth and periodontal repair and/or regeneration. We propose novel
      therapeutic approaches using stem cells or progenitor cells, which are targeted
      to regenerate the lost dental or periodontal tissue.

PMID- 21199331
TI  - Targeting the telomere and shelterin complex for cancer therapy: current views
      and future perspectives.
AB  - Aberrant telomere homeostasis is essential for cell immortality, enabling cells
      to evade telomere dependent senescence. Disruption of telomere structure and
      function in cancer cells is highly toxic as shown by detailed pre-clinical
      evaluation of telomerase inhibitors. Under telomerase inhibition, cells must
      divide sufficiently frequently to allow one or more telomeres to shorten to an
      unprotected length. Functioning telomeres are disguised from the DNA damage
      machinery by DNA remodelling and other activities of the telomere binding complex
      shelterin. Direct interference with shelterin has been shown to result in cell
      killing and small molecules directly targeting telomere DNA also have anti-tumour
      effects partially dependent on shelterin disruption. However, shelterin
      components have not generally been regarded as therapeutic targets in their own
      right. In this review, we explore the possibilities for therapeutic targeting of
      the shelterin complex.

PMID- 21199334
TI  - Apical fenestration and ectopic eruption - effects from trauma to primary tooth:
      a clinical case report.
AB  - The study describes a multidisciplinary treatment of fenestration in the apical
      of a primary maxillary right central incisor due a trauma and also its sequel, an
      ectopic eruption of the permanent maxillary right central incisor, on 7-year-old
      boy. Clinically, the primary tooth had an enamel and dentin fracture with no pulp
      exposure. There was an apical fenestration in the vestibular region, and the
      permanent tooth had an ectopic palatal eruption. The primary tooth was extracted,
      and for the physiological reposition of the permanent tooth, which was crossed
      with its antagonist, a Haas appliance was used for the rapid expansion of the
      maxilla for a period of 9 days.

PMID- 21199332
TI  - Histamine and H1 -histamine receptors faster venous circulation.
AB  - The study has analysed the action of histamine in the rabbit venous system and
      evaluated its potential role in contraction during increased venous pressure. We
      have found that a great variety exists in histamine sensitivity and H(1) 
      histamine receptor expression in various types of rabbit veins. Veins of the
      extremities (saphenous vein, femoral vein, axillary vein) and abdomen (common
      iliac vein, inferior vena cava) responded to histamine by a prominent,
      concentration-dependent force generation, whereas great thoracic veins
      (subclavian vein, superior vena cavas, intrathoracic part of inferior vena cava)
      and a pelvic vein (external iliac vein) exhibited slight sensitivity to exogenous
      histamine. The lack of reactivity to histamine was not due to increased activity
      of nitric oxide synthase (NOS) or heme oxygenase-1. H(1) -histamine receptor
      expression of veins correlated well with the histamine-induced contractions.
      Voltage-dependent calcium channels mediated mainly the histamine-induced force
      generation of saphenous vein, whereas it did not act in the inferior vena cava.
      In contrast, the receptor-operated channels were not involved in this response in
      either vein. Tyrosine phosphorylation occurred markedly in response to histamine
      in the saphenous vein, but not in the inferior vena cava. Histamine induced a
      prominent rho kinase activation in both vessels. Protein kinase C and mitogen
      activated protein kinase (MAPK) were not implicated in the histamine-induced
      intracellular calcium sensitization. Importantly, transient clamping of the
      femoral vein in animals caused a short-term constriction, which was inhibited by
      H(1) -histamine receptor antagonist in vivo. Furthermore, a significantly greater
      histamine immunopositivity was detected in veins after stretching compared to the
      resting state. We conclude that histamine receptor density adapts to the actual
      requirements of the circulation, and histamine liberated by the venous wall
      during increased venous pressure contributes to the contraction of vessels,
      providing a force for the venous return.

PMID- 21199335
TI  - Effects of traumatic dental injuries to primary teeth on permanent teeth--a
      clinical follow-up study.
AB  - AIM: This study evaluated the prevalence of developmental sequelae to permanent
      teeth (DSP) after traumatic dental injuries to primary teeth (TDI-1) and their
      association with age, gender, type of injury, recurrence of injury and post
      traumatic damage to primary teeth. MATERIALS AND METHODS: Dental records of 2725
      children treated from February 1993 to December 2008 in a private pediatric
      dental clinic were examined. A total of 308 records had 412 primary teeth that
      sustained traumatic injuries. Age at the time of injury ranged from 4 months to 7
      years. A chi-squared test and logistic regression were used for statistical
      analyses. RESULTS: One hundred forty-eight children (241 teeth) were followed up
      until the eruption of the permanent successor. The prevalence of DSP was 22.4%.
      Discoloration and hypoplasia were the most frequent abnormalities (74.1%),
      followed by eruption disorders (25.9%). Age at the time of TDI-1 was the only
      variable significantly associated with DSP. Sequelae were most prevalent among
      children who suffered an injury between 1 and 3 years of age. CONCLUSIONS:
      Children who sustain traumatic dental injuries should be followed up regularly
      for an early diagnosis and treatment of possible DSP.

PMID- 21199333
TI  - Repair mechanisms of bone marrow mesenchymal stem cells in myocardial infarction.
AB  - The prognosis of patients with myocardial infarction (MI) and resultant chronic
      heart failure remains extremely poor despite advances in optimal medical therapy
      and interventional procedures. Animal experiments and clinical trials using adult
      stem cell therapy following MI have shown a global improvement of myocardial
      function. Bone marrow-derived mesenchymal stem cells (MSCs) hold promise for
      cardiac repair following MI, due to their multilineage, self-renewal and
      proliferation potential. In addition, MSCs can be easily isolated, expanded in
      culture, and have immunoprivileged properties to the host tissue. Experimental
      studies and clinical trials have revealed that MSCs not only differentiate into
      cardiomyocytes and vascular cells, but also secrete amounts of growth factors and
      cytokines which may mediate endogenous regeneration via activation of resident
      cardiac stem cells and other stem cells, as well as induce neovascularization,
      anti-inflammation, anti-apoptosis, anti-remodelling and cardiac contractility in
      a paracrine manner. It has also been postulated that the anti-arrhythmic and
      cardiac nerve sprouting potential of MSCs may contribute to their beneficial
      effects in cardiac repair. Most molecular and cellular mechanisms involved in the
      MSC-based therapy after MI are still unclear at present. This article reviews the
      potential repair mechanisms of MSCs in the setting of MI.

PMID- 21199336
TI  - Eye injuries and orofacial traumas in floorball--a survey in Switzerland and
      Sweden.
AB  - The objective of this study was to investigate the occurrence of eye injuries and
      orofacial traumas in floorball. In addition, the athletes' habits of wearing
      protective goggles and mouthguards was surveyed, and an assessment was made of
      the general level of knowledge amongst athletes and coaches about preventive and
      first aid measures after a dental trauma and the resulting consequences. The
      study was conducted by the same interviewer in Switzerland and Sweden during the
      2009/2010 season using a standardized questionnaire. A total of 608 individuals
      (565 athletes and 43 coaches) belonging to the amateur and semi-professional
      leagues in the two countries were individually interviewed. Although 72.7% of all
      athletes had observed and 27.7% of field players had sustained an injury to the
      eye or its vicinity, only 25 athletes (4.9%) wore protective eyewear. Similarly,
      despite 31.7% of all players having observed a dental or jaw injury and 11.3% of
      interviewed field players having suffered one, only one athlete wore a mouthguard
      on a regular basis. Participants from Switzerland were significantly better
      informed than participants from Sweden with regard to first aid measures. The
      results of this study show that floorball has an equally high risk for dental
      trauma as handball. Further investigations of dental injuries in floorball would
      be valuable in order to provide players, coaches, parents and sporting
      federations with the necessary information to make decisions regarding the use of
      mouthguards. It is strongly recommended that protective eyewear should be made
      mandatory.

PMID- 21199337
TI  - Prevalence of dental trauma in individuals with special needs.
AB  - BACKGROUND: Individuals with special needs exist throughout the world. The last
      demographic census (IBGE, 2002) in Brazil indicated that 14.5% of the total
      population (24.5 million) present some type of impairment. This study aimed to
      evaluate the prevalence of dental trauma (DT) in individuals with special needs
      and the first attendance by a dental surgeon of patients admitted to the special
      care clinic of the School of Dentistry of Universidade Paulista (UNIP), Brazil,
      between 2001 and 2005. MATERIAL AND METHODS: The sample included 544 individuals
      with special needs aged 1-20 years old (mean 10.7 +/- SD 5.3). Patient medical
      records were reviewed for demographic and clinical data, including medical
      diagnosis, gender, age, presence of DT and whether the attendance provided was
      the first time the patient had sought dental treatment. RESULTS: The individuals
      were distributed into 11 subgroups according to medical diagnosis. The DT
      prevalence determined was 9.2% (n = 50), with no difference in relation to
      gender. The majority (78.3%) of the individuals were seeking dental treatment for
      the first time at an advanced age. CONCLUSIONS: The present data suggest that DT
      prevalence in individuals presenting special needs is more common in permanent
      dentition and that the first attendance by a dental surgeon is delayed.

PMID- 21199338
TI  - The AJT Report: News and issues that affect organ and tissue transplantation.
AB  - This month, "The AJT Report" explores the state of transplantation in Europe,
      takes a look at two recent live liver donor deaths, and highlights some hot
      topics covered at the first joint meeting of the European Society for Organ
      Transplantation and the American Society of Transplantation.

PMID- 21199341
TI  - Putting the IMPACT study into perspective: should CMV prophylaxis be extended to
      6 months for high risk transplants?

PMID- 21199342
TI  - Identification and targeting of costimulation-resistant T cells in renal
      transplantation.

PMID- 21199343
TI  - Native renal cysts and dialysis duration are risk factors for renal cell
      carcinoma in renal transplant recipients.

PMID- 21199344
TI  - The grading of donor complications: GPAs or pass/fail?

PMID- 21199345
TI  - Implementation of vascularized composite allografts in the United States:
      recommendations from the ASTS VCA Ad Hoc Committee and the Executive Committee.
AB  - Like all other areas of transplantation, vascularized composite allografts (VCA)
      has the capacity to transform the lives of patients, for the better or for the
      worse. It is this duality that mandates VCA be performed in centers prepared for
      the intricacies accompanying other transplant procedures. Similarly, the
      complexities of VCA require that the procedures be driven by surgeons and
      physicians with experience in the multidisciplinary management of
      immunocompromised postsurgical patients. Furthermore, the grafts should be
      considered as organs rather than tissues from a regulatory and a biological
      standpoint. The ASTS supports the field of VCA and has demonstrated its support
      and leadership by actively formulating a strategy for its systematic development.
      The goal of this document is to provide a framework for the prospective,
      thoughtful realization of VCA in the United States from the American Society of
      Transplant Surgeons (ASTS) perspective.

PMID- 21199346
TI  - IMPACT trial results should not change current standard of care of 100 days for
      cytomegalovirus prophylaxis.
AB  - The results of the IMPACT trial showed a significant reduction in cytomegalovirus
      disease with 200-day valganciclovir prophylaxis compared to the standard 100-day
      regimen with the same drug. These results may have the potential to change the
      standard of care in most transplant centers. However, we have concerns with the
      design, execution and statistical analysis of this trial. Our study aimed to
      describe each of these issues and to provide possible solutions for the better
      understanding of the IMPACT trial. We conclude that the IMPACT trial does not
      have the strength of evidence to change current clinical practice of 100-day
      cytomegalovirus prophylaxis. Further, based on all available evidence, we
      consider that another clinical trial to test 200-day CMV prophylaxis is not
      necessary.

PMID- 21199347
TI  - Cytomegalovirus latency promotes cardiac lymphoid neogenesis and accelerated
      allograft rejection in CMV naive recipients.
AB  - Human cytomegalovirus (HCMV) infection is associated with the acceleration of
      transplant vascular sclerosis (TVS) and chronic allograft rejection (CR). HCMV
      negative recipients of latently HCMV infected donor grafts are at highest risk
      for developing CMV disease. Using a rat heart transplant CR model, we have
      previously shown that acute rat CMV (RCMV) infection following transplantation
      significantly accelerates both TVS and CR. Here, we report that RCMV-naive
      recipients of heart allografts from latently RCMV-infected donors undergo
      acceleration of CR with similar kinetics as acutely infected recipients. In
      contrast to acutely infected recipients, treatment of recipients of latently
      infected donor hearts with ganciclovir did not prevent CR or TVS. We observed the
      formation of tertiary lymphoid structures (TLOs) containing macrophages and T
      cells in latently infected hearts prior to transplantation but not in uninfected
      rats. Moreover, pathway analysis of gene expression data from allografts from
      latently infected donors indicated an early and sustained production of TLO
      associated genes compared to allografts from uninfected donors. We conclude that
      RCMV-induced TLO formation and alteration of donor tissue T cell profiles prior
      to transplantation in part mediate the ganciclovir-insensitive rejection of
      latently infected donor allografts transplanted into naive recipients by
      providing a scaffold for immune activation.

PMID- 21199349
TI  - Import kidney transplants from nonmandatory share deceased donors:
      characteristics, distribution and outcomes.
AB  - Outcomes of locally rejected kidneys transplanted at other centers (import KTX)
      are unknown. SRTR data from 2000 to 2009 of deceased-donor KTXs excluding 0
      mismatch, paybacks, and other mandatory shares were compared by location of KTX
      at local (n = 48,165), regional (n = 4428) or national (n = 4104) centers using
      multivariable regression models. Compared to nonmandatory share local
      transplants, import KTX were associated with significantly higher overall risks
      of patient death (regional aHR 1.15, p < 0.01; national aHR 1.14, p < 0.01), and
      graft failure (regional aHR 1.17, p < 0.01; national aHR1.21, p < 0.01). In
      paired analysis, the risk of delayed graft function (DGF) for import KTX was
      higher compared to locally transplanted mates (regional aOR 1.53, p < 0.01,
      national aOR 2.14, p < 0.01); however, despite longer ischemia times, overall
      graft survival was similar. Mean cold ischemia times (CIT) pre- and post-DonorNet
      were similar for local and regional transplants, but significantly higher for
      national transplants (28.9 +/- 9.9 vs. 29.9 +/- 9.7 h, respectively, p = 0.01).
      Import KTX is associated with increased risks of graft failure, patient death and
      DGF. In the era of DonorNet cold ischemia times of kidneys imported to regional
      centers are not improved compared to pre-DonorNet; and, those of national centers
      are significantly prolonged.

PMID- 21199348
TI  - Significance of C4d Banff scores in early protocol biopsies of kidney transplant
      recipients with preformed donor-specific antibodies (DSA).
AB  - The significance of C4d-Banff scores in protocol biopsies of kidney transplant
      recipients with preformed donor-specific antibodies (DSA) has not been
      determined. We reviewed 157 protocol biopsies from 80 DSA+ patients obtained at 3
      months and 1 year post-transplant. The C4d Banff scores (1,2,3) were associated
      with significant increments of microcirculation inflammation (MI) at both 3
      months and 1 year post-transplant, worse transplant glomerulopathy and higher
      class II DSA-MFI (p < 0.01). Minimal-C4d had injury intermediate between negative
      and focal, while focal and diffuse-C4d had the same degree of microvascular
      injury. A total of 54% of patients had variation of C4d score between 3 months
      and 1 year post-transplant. Cumulative (3 month + 1 year) C4d scores correlated
      with long-term renal function worsening (p = 0.006). However, C4d staining was
      not a sensitive indicator of parenchymal disease, 55% of C4d-negative biopsies
      having evidence of concomitant MI. Multivariate analysis demonstrated that the
      presence of MI and class II DSA at 3 months were associated with a fourfold
      increased risk of progression to chronic antibody-mediated rejection
      independently of C4d (p < 0.05). In conclusion, the substantial fluctuation of
      C4d status in the first year post-transplant reflects a dynamic humoral process.
      However, C4d may not be a sufficiently sensitive indicator of activity, MI and
      DSA being more robust predictors of bad outcome.

PMID- 21199350
TI  - Efficacy and safety of continuous local infusion of ropivacaine after
      retroperitoneoscopic live donor nephrectomy.
AB  - Morphine-based analgesia is effective but can compromise donor safety. We
      investigated whether continuous infusion of local anesthetics (CILA) can provide
      sufficient pain control and reduce morbidity related to opiate analgesics after
      hand-assisted retroperitoneoscopic (HARS) live donor nephrectomy. Forty
      consecutive live kidney donors underwent HARS and were treated with the ON-Q
      system providing CILA with 0.5% ropivacaine through two SilvaGard catheters
      placed in the retroperitoneal cavity and the rectus sheath, respectively. The
      case control group consisted of 40 donors matched with regard to sex, age, BMI
      and surgical technique. All donors were maintained on standardized multimodal
      analgesia combining nurse-controlled oxycodone treatment and acetaminophen. CILA
      donors had lower median cumulative consumption of morphine equivalents (CCME) (7
      mg [0-56] vs. 42 mg [15-127]; p < 0.0000001), lower incidence of nausea (18 [45%]
      vs. 35 [87.5%] donors; p < 0.001), shorter time in postoperative care unit (160
      vs. 242.5 min; p < 0.001) and shorter hospital stay (4 [4-7] vs. 6 [4-11] days; p
      < 0.001). In 32.5% of CILA donors the CCME was 0 mg (0% in matched control group,
      p < 0.001). CILA with 0.5% ropivacaine provides effective postoperative pain
      relief, reduces the need for opioid treatment and promotes postoperative
      recovery.

PMID- 21199351
TI  - Short- and long-term donor morbidity in right lobe living donor liver
      transplantation: 91 consecutive cases in a European Center.
AB  - The lack of use of a common grading system in reporting morbidity impedes
      estimation of the true risk to a right lobe living donor (RLLD). We report
      outcomes in 91 consecutive RLLD's using the validated 5-tier Clavien grading and
      a quality of life (QOL) questionnaire. The median follow-up was 79 months. The
      donors were predominantly female (66%), 22 (24%) received autologous blood
      transfusions. Fifty-three complications occurred in 43 donors (47% morbidity), 19
      (37%) were >= Grade III, biliary fistula (14%) was the most common. There was no
      donor mortality. Two intraoperative complications could not be graded and two
      disfiguring complications in female donors were graded as minor. Two subgroups
      (first 46 vs. later 45 donors) were compared to study the presence if any, of a
      learning curve. The later 45 donors had lesser autologous transfusions, lesser
      rehospitalization and no reoperation and a reduction in the proportion of >=
      Grade III (major) complications (24% vs. 50%; p = 0.06). In the long term, donors
      expressed an overall sense of well being, but some sequelae of surgery do
      restrain their current lifestyle. Our results warn against lackadaisical
      vigilance once RLLD hepatectomy becomes routine.

PMID- 21199353
TI  - Interaction of antithymocyte globulins with dendritic cell antigens.
AB  - The polyclonal rabbit antithymocyte globulins (ATGs), Thymoglobulin and ATG
      Fresenius S, are widely used for prevention and therapy of allograft rejection
      and graft versus host disease. Dendritic cells (DC) govern immune responses and
      thus the interaction of ATGs with these cells could potentially contribute to the
      clinical effects of ATG therapy. Currently there is little information on the DC
      antigens targeted by ATGs. In this study we have used a new methodology to
      identify DC surface antigens recognized by ATGs. By screening an eukaryotic
      expression library generated from DC with ATGs we could identify several novel
      ATG antigens including CD81, CD82, CD98, CD99 and CD147. Furthermore, we
      engineered cells to express previously described ATG antigens and probed them
      with Thymoglobulin and ATG-Fresenius S. Our results demonstrated strong binding
      to some but not all of these molecules. We show that previously described
      antigens and antigens identified in this study account for around 80% of the DC
      reactivity of ATGs. Analysis of molecules induced by ATG-DC interaction are more
      in support for an activation of these cells by ATGs than for a specific induction
      of a tolerogenic DC phenotype.

PMID- 21199352
TI  - Improved survival in pediatric heart transplant recipients: have white, black and
      Hispanic children benefited equally?
AB  - We assessed whether the improvement in posttransplant survival in pediatric heart
      transplant (HT) recipients during the last two decades has benefited the major
      racial groups in the United States equally. We analyzed all children <18 years of
      age who underwent their first HT in the US during 1987-2008. We compared trends
      in graft loss (death or retransplant) in white, black and Hispanic children in
      five successive cohorts (1987-1992, 1993-1996, 1997-2000, 2001-2004, 2005-2008).
      The primary endpoint was early graft loss within 6 months posttransplant. Longer
      term survival was assessed in recipients who survived the first 6 months. The
      improvement in early posttransplant survival was similar (hazard ratio [HR] for
      successive eras 0.80, 95% confidence interval [CI] 0.7, 0.9, p = 0.24 for black
      era interaction, p = 0.22 for Hispanic-era interaction) in adjusted analysis.
      Longer-term survival was worse in black children (HR 2.2, CI 1.9, 2.5) and did
      not improve in any group with time (HR 1.0 for successive eras, CI 0.9, 1.1, p =
      0.57; p = 0.19 for black-era interaction, p = 0.21 for Hispanic-era interaction).
      Thus, the improvement in early post-HT survival during the last two decades has
      benefited white, black and Hispanic children equally. Disparities in longer-term
      survival have not narrowed with time; the survival remains worse in black
      recipients.

PMID- 21199354
TI  - Pediatric organ transplantation and risk of premalignant and malignant tumors in
      Sweden.
AB  - Increased cancer risks are well documented in adult organ transplant recipients.
      However, the spectrum of malignancies and risk in the pediatric organ transplant
      population are less well described. We identified all solid organ transplanted
      patients aged <18 in Sweden between 1970-2007 (n = 536) in the National Patient
      Register and linked to the Cancer Register. Nationwide rates were used to
      calculate standardized incidence rate ratios and 95% CI estimating the
      association between transplant and cancer during maximum 36 years of follow-up.
      Nearly 7% of pediatric solid organ transplant recipients developed a premalignant
      or malignant tumor during follow-up. Transplantation was associated with an
      increased risk of any cancer (n = 24, SIR = 12.5, 95% CI: 8.0-18.6): non-Hodgkin
      lymphoma (NHL) (n = 13, SIR = 127, 95% CI: 68-217), renal cell (n = 3, SIR = 105,
      95% CI: 22-307), vulva/vagina (n = 3, SIR = 665, 95% CI: 137-1934) and
      nonmelanoma skin cancers (n = 2, SIR = 64.7, 95% CI: 7.8-233.8). NHL typically
      appeared during childhood, while other tumors were diagnosed during adulthood.
      Apart from short-term attention toward the potential occurrence of NHL, our
      results suggest cancer surveillance into adulthood with special attention to
      skin, kidneys and the female genitalia.

PMID- 21199355
TI  - Kidney transplant from the same donor without maintenance immunosuppression after
      previous hematopoietic stem cell transplant.
AB  - In January 2005, an 18-year-old male patient with acute myeloid leukemia (AML)
      received a haploidentical hematopoietic stem cell transplantation (HSCT) from his
      father. He developed hemolytic uremic syndrome and end-stage renal disease (ESRD)
      requiring hemodialysis on day 357 after HSCT. On day 1020 after HSCT, a living
      kidney donation from the stem cell donor was carried out. The creatinine before
      kidney transplantation (KT) was ~450 MUmol/L, 268 MUmol/L on day 2 after KT, 88
      MUM on day 38 and 89 MUmol/L on day 960 (day 1980 after HSCT). Immunosuppression
      was gradually discontinued: cortisone on day 28, tacrolimus on day 32 and MMF on
      day 100 after KT (day 1120 after HSCT). As of June 2010, 66 months after HSCT and
      32 months after KT, the patient has had neither rejection episodes nor clinical
      manifestations of transplantation-related complications. The patient reached 100%
      hematopoietic donor chimerism prekidney transplant and retained this state
      postkidney transplant. This unique case is the first report of a successful
      kidney transplant without immunosuppression after HSCT from the same
      haploidentical donor.

PMID- 21199356
TI  - Three cases of alopecia following clinical islet transplantation.
AB  - Successful clinical islet allotransplantation requires control of both allo- and
      autoimmunity by using immunosuppressant drugs which have a number of side
      effects. The development of the autoimmune condition alopecia areata following
      successful islet transplantation is therefore unexpected. Three cases of alopecia
      affecting female islet transplant recipients are described. In all cases,
      alopecia developed approximately 7 years after initial transplant. All had
      received daclizumab, sirolimus and tacrolimus with their initial transplants, but
      all were receiving a combination of tacrolimus and mycophenolate mofetil at the
      time alopecia developed. Two subjects had received thymoglobulin for a subsequent
      islet infusion and prior to the onset of alopecia. The progression of alopecia
      has been halted or reversed in all cases. Tacrolimus has been continued in two
      cases (one as monotherapy) while cyclosporine was used in place of tacrolimus in
      the third case. These three cases represent a crude incidence of <2.5% over 5
      years compared with a prevalence of alopecia in islet transplant candidates
      (pretransplant) of <1%. Although alopecia might be expected in a proportion of
      individuals with type 1 diabetes, the risk may be increased after islet
      transplantation, and may be associated with the use of anti-TNF drugs,
      lymphodepleting antibodies or higher dose tacrolimus.

PMID- 21199357
TI  - Post-liver transplantation multicentric Castleman disease treated with
      valganciclovir and weaning of immunosuppression.
AB  - Multicentric Castleman disease is a lymphoproliferative disorder which when seen
      in the setting of HIV/AIDS is often associated with human herpes virus 8 (HHV-8)
      infection. We describe the case of a HIV-negative man who developed HHV-8
      associated multicentric Castleman disease 11 years after liver transplantation.
      The patient presented with fevers and weight loss. Physical examination revealed
      enlarged cervical, axillary and inguinal lymph nodes. Widespread lymphadenopathy
      was confirmed on computed tomography (CT) scanning. Histology of an enlarged
      lymph node showed a polymorphous infiltrate with mature plasma cells,
      plasmacytoid lymphocytes and occasional blasts within the cortex and paracortex.
      The diagnosis of Castleman disease was confirmed by the finding of numerous HHV-8
      immunopositive cells around the regressed lymph node follicles and the detection
      of HHV-8 on plasma PCR. Although the conventional treatment for this condition
      has been combination chemotherapy, in the post-transplant context it was decided
      to treat the patient with valganciclovir and cessation of immunosuppression. His
      symptoms resolved rapidly and repeat plasma PCR done 3 months after starting
      treatment was negative for HHV-8. A follow-up CT scan showed a dramatic reduction
      in the size and amount of lymphadenopathy. After 15 months of treatment, he
      remains well with no evidence of graft dysfunction or rejection.

PMID- 21199360
TI  - Response to questions regarding the design and results of the IMPACT trial.

PMID- 21199361
TI  - Response: Good ethics require good science: why transplant programs should not
      disclose misattributed parentage.

PMID- 21199364
TI  - The small bowel contained allografts: existing and proposed nomenclature.

PMID- 21199365
TI  - Malignant glomus tumor of the trunk treated with Mohs micrographic surgery.

PMID- 21199366
TI  - Nickel-induced Koebner phenomenon in chronic cutaneous lupus erythematosus.

PMID- 21199367
TI  - Hypothalamic malonyl-CoA and CPT1c in the treatment of obesity.
AB  - Metabolic integration of nutrient sensing in the central nervous system has been
      shown to be an important regulator of adiposity by affecting food intake and
      peripheral energy expenditure. Modulation of de novo fatty acid synthetic flux by
      cytokines and nutrient availability plays an important role in this process.
      Inhibition of hypothalamic fatty acid synthase by pharmacologic or genetic means
      leads to an increased malonyl-CoA level and suppression of food intake and
      adiposity. Conversely, the ectopic expression of malonyl-CoA decarboxylase in the
      hypothalamus is sufficient to promote feeding and adiposity. Based on these and
      other findings, metabolic intermediates in fatty acid biogenesis, including
      malonyl-CoA and long-chain acyl-CoAs, have been implicated as signaling mediators
      in the central control of body weight. Malonyl-CoA has been hypothesized to
      mediate its effects in part through an allosteric interaction with an atypical
      and brain-specific carnitine palmitoyltransferase-1 (CPT1c). CPT1c is expressed
      in neurons and binds malonyl-CoA, however, it does not perform the same
      biochemical function as the prototypical CPT1 enzymes. Mouse knockout models of
      CPT1c exhibit suppressed food intake and smaller body weight, but are highly
      susceptible to weight gain when fed a high-fat diet. Thus, the brain can directly
      sense and respond to changes in nutrient availability and composition to affect
      body weight and adiposity.

PMID- 21199368
TI  - Adipocyte hyperplasia and RMI1 in the treatment of obesity.
AB  - The escalating prevalence of obesity is one of the most pressing health concerns
      of the modern era, yet existing medicines to combat this global pandemic are
      disappointingly limited in terms of safety and effectiveness. The inadequacy of
      currently available therapies for obesity has made new drug development crucial.
      In the past several decades, however, major progress has been achieved in
      understanding adipocyte hyperplasia associated with the pathogenesis of obesity,
      and consequently new potential targets for the medical treatment of obesity have
      been identified. We primarily review recent progress in the regulation of
      adipocyte hyperplasia as a novel emerging nontraditional approach. In this
      minireview, we focus on recQ-mediated genome instability 1 (RMI1), a recently
      identified novel molecular target for obesity treatment. RMI1-deficient mice have
      been found to be resistant to high-fat diet- and genetics-related obesity.
      Expression of this protein is regulated by E2F transcription factors, and recent
      studies have suggested that RMI1 plays an important role in the control of energy
      homeostasis during the development of obesity, with a mode of action based on the
      regulation of adipocyte hyperplasia.

PMID- 21199369
TI  - Design of hairpin ribozyme variants with improved activity for poorly processed
      substrates.
AB  - Application of ribozymes for knockdown of RNA targets requires the identification
      of suitable target sites according to the consensus sequence. For the hairpin
      ribozyme, this was originally defined as Y-2 N-1 *G+1 U+2 Y+3 B+4, with Y = U or
      C, and B = U, C or G, and C being the preferred nucleobase at positions -2 and
      +4. In the context of development of ribozymes for destruction of an oncogenic
      mRNA, we have designed ribozyme variants that efficiently process RNA substrates
      at U-2 G-1 *G+1 U+2 A+3 A+4 sites. Substrates with G-1 *G+1 U+2 A+3 sites were
      previously shown to be processed by the wild-type hairpin ribozyme. However, our
      study demonstrates that, in the specific sequence context of the substrate
      studied herein, compensatory base changes in the ribozyme improve activity for
      cleavage (eight-fold) and ligation (100-fold). In particular, we show that A+3
      and A+4 are well tolerated if compensatory mutations are made at positions 6 and
      7 of the ribozyme strand. Adenine at position +4 is neutralized by G6 ->U, owing
      to restoration of a Watson-Crick base pair in helix 1. In this ribozyme-substrate
      complex, adenine at position +3 is also tolerated, with a slightly decreased
      cleavage rate. Additional substitution of A7 with uracil doubled the cleavage
      rate and restored ligation, which was lost in variants with A7, C7 and G7. The
      ability to cleave, in conjunction with the inability to ligate RNA, makes these
      ribozyme variants particularly suitable candidates for RNA destruction.

PMID- 21199370
TI  - Roles of the SH2 and SH3 domains in the regulation of neuronal Src kinase
      functions.
AB  - Previous studies demonstrated that intra-domain interactions between Src family
      kinases (SFKs), stabilized by binding of the phosphorylated C-terminus to the SH2
      domain and/or binding of the SH2 kinase linker to the SH3 domain, lock the
      molecules in a closed conformation, disrupt the kinase active site, and
      inactivate SFKs. Here we report that the up-regulation of N-methyl-D-aspartate
      receptors (NMDARs) induced by expression of constitutively active neuronal Src (n
      Src), in which the C-terminus tyrosine is mutated to phenylalanine (n-Src/Y535F),
      is significantly reduced by dysfunctions of the SH2 and/or SH3 domains of the
      protein. Furthermore, we found that dysfunctions of SH2 and/or SH3 domains reduce
      auto-phosphorylation of the kinase activation loop, depress kinase activity, and
      decrease NMDAR phosphorylation. The SH2 domain plays a greater regulatory role
      than the SH3 domain. Our data also show that n-Src binds directly to the C
      terminus of the NMDAR NR2A subunit in vitro, with a K(D) of 108.2 +/- 13.3 nM.
      This binding is not Src kinase activity-dependent, and dysfunctions of the SH2
      and/or SH3 domains do not significantly affect the binding. These data indicate
      that the SH2 and SH3 domains may function to promote the catalytic activity of
      active n-Src, which is important in the regulation of NMDAR functions.

PMID- 21199371
TI  - Thermodynamic analysis of Jun-Fos coiled coil peptide antagonists.
AB  - Dimerization of the Jun-Fos activator protein-1 (AP-1) transcriptional regulator
      is mediated by coiled coil regions that facilitate binding of the basic regions
      to a specific promoter. AP-1 is responsible for the regulation of a number of
      genes involved in cell proliferation. We have previously derived peptide
      antagonists and demonstrated them to be capable of binding to the Jun or Fos
      coiled coil region with high affinity (K(D) values in the low nM range relative
      to MUM for the wild-type interaction). Use of isothermal titration calorimetry
      combined with CD spectroscopy is reported to elucidate the thermodynamic
      parameters that drive the interaction stability of peptide antagonists with their
      cJun and cFos targets. We observe that the free energy of binding for antagonist
      target complexes is dominated by the enthalpic term, is opposed by unfavourable
      entropic contributions consistent with reduced conformational freedom and that
      these values in turn correlate well (r = -0.97) with the measured helicity of
      each dimeric pair. The more helical the antagonist-target complex, the more
      favourable the change in enthalpy, which is in turn opposed more strongly by
      entropy. Antagonistic peptides are predicted to represent excellent scaffolds for
      further refinement. By contrast, the wild-type cJun-cFos complex is dominated by
      a favourable entropic contribution, owing partially to a decrease in buried
      hydrophobic groups from cFos core residues and an increase in the conformational
      freedom.

PMID- 21199372
TI  - A functional polymorphism in the CYP3A4 gene is associated with increased risk of
      coronary heart disease in the Chinese Han population.
AB  - CYP3A4 is a major member of the cytochrome P450 (CYP) enzymes which play crucial
      roles in cardiovascular diseases. Recently, a novel polymorphism in the CYP3A4
      gene, IVS10+12G>A, named CYP3A4*1G (rs2242480), has been identified. The aim of
      this study was to evaluate the potential relationship between the CYP3A4*1G
      allele and the susceptibility of coronary heart disease (CHD). A total of 628
      individuals (322 unrelated patients with CHD and 306 age- and sex-matched healthy
      controls) were investigated in the study. Polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) was used to identify CYP3A4*1G. We also
      analysed the functional significance of IVS10+12G>A using the dual-luciferase
      reporter assay. The results showed that the frequency of the CYP3A4*1G allele was
      0.290 and the CYP3A4*1G/*1G genotype was 0.090 in the patients with CHD. The
      patients with the CYP3A4*1G/*1G genotype had higher CHD risk, with an odds ratio
      (OR) of 3.84 (p=0.025; 95% CI=1.32-12.65) after adjustment for conventional risk
      factors. A gender-dependent difference was also observed. The CYP3A4*1G/*1G
      frequency was significantly higher in female patients than in the controls
      (p=0.034, OR=3.02, 95% CI=1.04-8.70). Furthermore, the dual-luciferase reporter
      assay indicated that the A allele at IVS10+12G>A had a significantly higher
      transcriptional activity than the G allele. Our results imply that CYP3A4*1G
      contributes to the susceptibility of CHD in the Chinese Han population, which may
      be useful for the study of specific molecular pathogenesis for CHD.

PMID- 21199373
TI  - The growing concerns regarding counterfeit medications.

PMID- 21199374
TI  - ISSM public policy statement.

PMID- 21199375
TI  - No-touch technique.

PMID- 21199377
TI  - Sexual function after breast cancer.
AB  - INTRODUCTION: Breast cancer (BC) remains the most common non-skin cancer in women
      and an increasing number are living as BC survivors. AIM: The aim of this article
      is to evaluate the impact of the first diagnosis of invasive BC and its
      treatment, menopausal symptoms, and body image on sexual function. METHODS: The
      BUPA Foundation Health and Wellbeing after Breast Cancer Study is a prospective
      cohort study of 1,684 women recruited within 12 months of their first diagnosis
      with invasive BC. Each participant completed an enrollment questionnaire (EQ) and
      first follow-up questionnaire (FQ1) 12 months post-EQ. MAIN OUTCOME MEASURE:
      Sexual function was evaluated by the Menopause-Specific Quality of Life
      Questionnaire embedded within the FQ1. RESULTS: Of the 1,011 women in the
      analyses, 70% experienced sexual function problems and 77% reported vasomotor
      symptoms. Women experiencing sexual function problems were postmenopausal (P =
      0.02), experienced vasomotor symptoms (P < 0.01), and used aromatase inhibitors
      (P = 0.03). Women with vasomotor symptoms were twice as likely to experience
      sexual function problems (odds ratio [OR] 1.93, 95% confidence interval [CI] 141,
      2.63; P < 0.001). This association was more extreme for women on aromatase
      inhibitors (OR 3.49, 95% CI 1.72, 7.09; P = 0.001) but did not persist in women
      not using endocrine therapies (OR 1.41, 95% CI 0.84, 2.36; P = 0.19). Women on
      aromatase inhibitors were more likely to report sexual function problems (OR
      1.50, 95% CI 1.0, 2.2, P = 0.04) and women with body image issues were 2.5 times
      more likely to report sexual function problems (OR 2.5 95% CI 1.6, 3.7, P <
      0.001). Women using tamoxifen were not more likely to experience sexual function
      problems (OR 1.1, 95% CI 0.8, 1.5, P = 0.6); however, women with body image
      issues were twice as likely to experience sexual function problems (OR 2.1, 95%
      CI 1.5, 3.0, P < 0.001). CONCLUSION: Seventy percent of partnered BC survivors
      less than 70 experienced sexual function problems. Sexual problems are related to
      the use of aromatase inhibitors which can exacerbate menopausal symptoms.

PMID- 21199378
TI  - Improvement science: getting the evidence into practice.

PMID- 21199379
TI  - Systematic review of current executive function measures in adults with and
      without cognitive impairments.
AB  - BACKGROUND: Executive function pertains to higher cognitive processes
      historically linked to frontal lobes. Several measures are available to screen
      for executive function; however, no gold standard exists. The difficulty in
      assessing executive function is the existence of its many subsets. OBJECTIVES: To
      evaluate the psychometric properties of executive function measures and determine
      the most effective measure(s) through a systematic review of the literature.
      SEARCH STRATEGY: The search strategy utilised a comprehensive literature review
      of articles written in the English language published from January 2003 to
      September 2009. The following electronic databases were searched: SCOPUS, PUBMED,
      Medline Ovid, PsychArticles and CINAHL Plus. Initial key words used were
      'executive function', 'measures', 'reliability' and 'validity' followed by the
      addition of 'traumatic brain injury'. The initial search elicited 226 articles,
      of which 28 were retrieved. After further exclusion 19 were included in the
      review. RESULTS: Eight measures underwent factor analysis and 18 underwent
      various forms of reliability and/or validity testing. Factor analysis showed
      different aspects of executive functions. According to preset evaluation
      criteria, only the Test of Practical Judgment performed all of the recommended
      reliability and validity testing. REVIEWER'S CONCLUSION: Of the recently
      developed measures, several show promise for future use yet further validity and
      reliability testing is warranted. Future tool development should measure all
      subsets of executive function rather than only a few and include the recommended
      components of reliability and validity testing.

PMID- 21199380
TI  - Appropriateness of using a symbol to identify dementia and/or delirium.
AB  - AIM: The main objective of this systematic review was to evaluate any published
      and unpublished evidence regarding the appropriateness of developing a symbol for
      dementia and/or delirium, which could be used in a variety of settings to
      indicate that a person has dementia and/or delirium. METHODS: Using the methods
      of the Joanna Briggs Institute, we conducted a systematic search of a wide range
      of databases, Internet resources and unpublished literature. Papers meeting the
      inclusion criteria were critically appraised by two independent reviewers. Data
      were extracted, using the standardised tool from the Joanna Briggs Institute,
      from those papers considered to be of sufficient quality. Because of significant
      methodological heterogeneity, no meta-analysis was possible and results are
      presented narratively instead. RESULTS: From a total of 37 retrieved papers, 18
      were found to be of sufficient relevance and quality to be included in the
      review. There was general consensus among the literature that a symbol for
      dementia is appropriate in the acute care setting. It was also clear from the
      research that an abstract symbol, as opposed to one that explicitly attempts to
      depict dementia, was most acceptable to staff, people with dementia and their
      carers. CONCLUSIONS: Both staff and health consumers seem to have largely
      positive perceptions and attitudes towards the use of a symbol for dementia.
      Families and carers of people with dementia are frequently concerned about their
      loved one wandering away and becoming lost and unable to identify themselves, and
      these concerns seem to outweigh any reservations they hold about the use of a
      symbol or some other identifier. In healthcare settings the use of symbols to
      indicate special needs seems well established and widely accepted. However,
      regarding the use of a symbol for dementia in the broader community, there remain
      concerns about issues such as stigmatisation and the potential for victimisation
      of this vulnerable population and so further research is indicated.

PMID- 21199381
TI  - Relationship between periodontal disease and osteoporosis.
AB  - BACKGROUND: For many years an association between the low bone density of
      osteoporosis and increased risk of periodontal bone loss has been suspected. In
      this review the relationship between osteoporosis and periodontal disease is
      considered. METHODS: For this narrative review a very broad search strategy of
      the literature was developed using both PubMed and Scopus databases using the
      search words "perio" and "osteoporosis". The reference lists from the selected
      papers were also scanned and this provided an additional source of papers for
      inclusion. The inclusion/exclusion criteria, were also quite liberal with only
      those papers dealing with bisphosphonates and osteonecrosis of the jaws,
      osteoporosis in edentulous individuals, as well as those not written in English
      being excluded. RESULTS: The data available suggest that reduced bone mineral
      density is a shared risk factor for periodontitis rather than a causal factor.
      However, more prospective studies are required to fully determine what, if any,
      relationship truly exists between periodontitis and reduced bone mineral density.
      CONCLUSIONS: More prospective studies are required to determine what, if any,
      relationships exist between periodontal disease and reduced bone mineral density.

PMID- 21199382
TI  - Gaps in the evidence about companion animals and human health: some suggestions
      for progress.
AB  - A number of researchers have explored the relationship between companion animal
      ownership and human physical and psychological health. Results have been
      inconclusive, with positive, neutral and negative effects variously reported in
      the literature. Furthermore, the possible mechanisms of any influence are
      frustratingly unclear. A number of conceptual and methodological weaknesses have
      hampered progress in our understanding of how companion animals may impact upon
      human health. The two evidence gaps discussed in this paper, with suggestions for
      needed next steps, are: (i) a preponderance of anecdotal reports and cross
      sectional research designs; and (ii) failure to control for a host of other known
      influences on human health including health habits, level of attachment to the
      companion animal and human social supports. Finally, an example of these gaps is
      provided in relation to the literature on the effects of animals on elderly
      nursing home residents.

PMID- 21199383
TI  - Summaries of nursing care-related systematic reviews from the Cochrane Library:
      Topical capsaicin for chronic neuropathic pain in adults.

PMID- 21199384
TI  - Summaries of nursing care-related systematic reviews from the Cochrane Library:
      Intra-amniotic surfactant for preventing respiratory distress in newborns.

PMID- 21199385
TI  - Summaries of nursing care-related systematic reviews from the Cochrane Library:
      Ear drops for the removal of ear wax.

PMID- 21199386
TI  - Summaries of nursing care-related systematic reviews from the Cochrane Library:
      Bed rest for acute low-back pain and sciatica.

PMID- 21199388
TI  - IL-6 SNP diversity among four ethnic groups as revealed by bead-based liquid
      array profiling.
AB  - In the present work, we established a rapid, cost-effective and high-throughput
      method for genotyping using a multiplexed microsphere-based suspension array
      platform - Luminex((r)) *MAPTM, which enabled us to analyse two SNPs in the
      promoter of IL-6 gene, determining haplotypes associated with different levels of
      expression. Using this system, IL-6 diversity in four different ethnic groups -
      East Asians, Caucasians, Hispanic and African Americans - was assessed. Results
      showed a significant variability in terms of allele, genotype and haplotype
      distribution. Considering the important immunoregulatory role of this cytokine
      and as a clinically relevant marker, this genotyping approach will provide a
      powerful tool for disease association or transplant outcome studies.

PMID- 21199389
TI  - The HLA-B*83:01 allele is generated by a gene conversion event including whole of
      exon 2 and partial introns 1 and 2 between B*44 and B*56 alleles.
AB  - Several studies have indicated the gene conversion as the most important
      mechanism about the MHC polymorphism generation when intron sequences are
      studied. The data obtained confirm that the B*83:01 allele is generated by gene
      conversion event including exon 2 and partial intron 1 and 2 between B*44 and
      B*56 alleles.

PMID- 21199392
TI  - Mapping quantitative trait loci for innate immune response in the pig.
AB  - The aim of the present study was to detect quantitative trait loci (QTL) for the
      serum levels of cytokines and Toll-like receptors as traits related to innate
      immunity in pig. For this purpose, serum concentration of interleukin 2 (IL2),
      interleukin 10 (IL10), interferon-gamma (IFNG), Toll-like receptor 2 (TLR2) and
      Toll-like receptor 9 (TLR9) were measured in blood samples obtained from F(2)
      piglets (n = 334) of a Duroc * Pietrain resource population (DUPI) after
      Mycoplasma hypopneumoniae (Mh), tetanus toxoid (TT) and Porcine Reproductive and
      Respiratory Syndrome Virus (PRRSV) vaccination at 6, 9 and 15 weeks of age.
      Animals were genotyped at 82 genetic markers covering all autosomes. QTL analysis
      was performed under the line cross F(2) model using QTL Express and 33 single QTL
      were detected on almost all porcine autosomes. Among the single QTL, eight,
      twelve and thirteen QTL were identified for innate immune traits in response to
      Mh, TT and PRRSV vaccine, respectively. Besides single QTL, six QTL were
      identified by a two-QTL model, of which two for TLR9_TT were in coupling phase
      and one for IL10_PRRSV was in repulsion phase. All QTL were significant at 5%
      chromosome-wide level including one and seven at 5% genome- and 1% chromosome
      wide level significance. All innate immune traits are influenced by multiple
      chromosomal regions implying multiple gene action. Some of the identified QTL
      coincided with previously reported QTL for immune response and disease
      resistance, and the newly identified QTL are potentially involved in the immune
      function. The immune traits were also influenced by environmental factors like
      year of birth, age, parity and litter size. The results of this work shed new
      light on the genetic background of innate immune response and these findings will
      be helpful to identify candidate genes in these QTL regions related to immune
      competence and disease resistance in pigs.

PMID- 21199393
TI  - Lack of association between IL-1 and IL-6 gene polymorphisms and myocardial
      infarction in Turkish population.
AB  - Inflammation and genetics play a key role in the pathogenesis of atherosclerosis
      and its clinical result myocardial infarction (MI). Proinflammatory cytokines, IL
      1 and IL-6, have been shown to play essential roles in developmental stages of
      coronary artery plaque formation. The aim of this study was to determine the
      association between IL-1 [IL-1RN, IL-1beta (-511, +3953)], IL-6 [-174, -572, 
      597] gene polymorphisms and MI in Turkish population. A total of 402 people were
      participated; 235 healthy control subjects and 167 MI patients (MI<40, n: 72;
      MI>40, n: 95). Polymerase chain reaction (PCR) was used to determine the genotype
      of IL-1RN, whereas the genotypes of IL-1beta (-511, +3953) and IL-6 (-174, -572, 
      597) were determined using PCR followed with restriction digestion analysis.
      There was no significant difference between MI and controls for IL-1RN, IL-1beta
      511, +3953 (P: 0.875, 0.608, 0.442) and IL-6 -174, -572, -597 (P: 0.977, 0.632,
      0.584) gene polymorphisms. Lack of association was observed between MI at younger
      age (MI<40) and either IL-1RN VNTR, IL-1beta-511, +3953 (P: 0.878, 0.732, 0.978)
      or IL-6 -174, -572, -597 (P: 0.313, 0.654, 0.552) gene polymorphisms. This study
      demonstrated that there was not any association between IL-1, IL-6 gene variants
      and MI in Turkish population. In addition, IL-1 and IL-6 gene polymorphisms did
      not affect MI at younger age (MI<40) or older age (MI>40). Thus, IL-1 and IL-6
      single nucleotide polymorphisms may not be a risk factor for susceptibility to MI
      in Turkish population.

PMID- 21199394
TI  - H2AX gene does not have a modifier effect on ataxia-telangiectasia phenotype.
AB  - Ataxia-telangiectasia (AT) is a complex disorder characterized by progressive
      neurodegeneration, immunodeficiency, hypersensitivity to DNA damaging agents and
      cancer predisposition. Clinical heterogeneity is observed even among the affected
      siblings with AT. Mutations of the ataxia-telangiectasia mutated (ATM) gene are
      responsible for AT. H2AX, an essential histone protein, is phosphorylated by ATM
      in response to double-strand breaks, and H2AX-deficient mice share some clinical
      and laboratory findings with AT. Therefore, we sought a possible modifier effect
      of H2AX gene on various clinical features in a group of patients with AT and
      healthy controls. We performed sequence analysis of H2AX gene in 81 patients with
      AT, and in 51 of them, we analysed methylation. We examined H2AX gene expression
      in 25 patients. We investigated 48 healthy individuals as a control group. We did
      not detect any mutation or sequence variation in the H2AX gene, or any altered
      methylation pattern in any of the patients. Although H2AX gene expression was
      markedly increased (2.5- to 11.8-fold) in five of 25 patients, and slightly
      increased (1.5- to 2.4-fold) in four patients, the correlations between H2AX gene
      expression and the evaluated clinical features of the patients were not
      significant. Other potential modifier genes that might be scrutinized in AT
      patients include p53, 53BP1 and TIP60, as well as the genes that effect
      mitochondrial function and the oxidative response.

PMID- 21199396
TI  - Magnitude of the Root effect in red blood cells and haemoglobin solutions of
      fishes: a tribute to August Krogh.
AB  - AIM: The ability of high carbon dioxide tensions or low pH to reduce blood oxygen
      binding even at high oxygen tensions, first observed by August Krogh and Isabella
      Leitch in 1919 and now known as the Root effect, was studied in red blood cells
      and haemoglobin solutions of several fish species. METHODS: Red blood cells in
      physiological saline were acidified at atmospheric oxygen tension by increasing
      carbon dioxide tensions and the percentage decrease in oxygen content was used to
      quantify the Root effect. Haemoglobin was incubated in air-equilibrated citrate
      buffers between pH 5 and 7 and the percentage decrease in oxygen saturation
      relative to pH 8 determined by spectral deconvolution. RESULTS: The maximal
      magnitude of the Root effect in citrate-buffered haemoglobin solutions closely
      matched the value in blood or red blood cells of 11 vertebrates over a Root
      effect range between 3 and 80%. Contrary to previous reports, there was no
      evidence for a significant Root effect in red blood cells or haemoglobin
      solutions of the wels catfish, but a significant Root effect under both
      conditions in the Siberian sturgeon. CONCLUSIONS: Under the conditions employed
      in this study, the maximal Root effect of citrate-buffered haemoglobin solutions
      closely resembles the maximal Root effect in red blood cells. This strengthens
      previous studies on the evolution of the Root effect and its role in oxygen
      concentration at the retina and swimbladder of a large number of fishes that were
      based on Root effect measurements in haemoglobin solutions.

PMID- 21199398
TI  - The effect of arterial wall shear stress on the incremental elasticity of a
      conduit artery.
AB  - AIMS: The purpose of this investigation was to determine the effects of flow
      mediated dilatation on arterial incremental elasticity (E(inc) ). METHODS:   In
      four female anaesthetized pigs, the iliac artery and vein were connected by a
      shunt with a variable resistance which allowed blood flow and therefore shear
      stress to be regulated. E(inc) was calculated from simultaneous records of
      diameter and pressure throughout a minimum of four cardiac cycles. RESULTS:
      Passive increases in diameter (~1-2%) throughout a cardiac cycle, brought about
      by pressure, resulted in a two- to threefold increase in E(inc) . In contrast,
      increases in shear stress caused active smooth muscle relaxation and a
      significant increase in diameter from 3.663 +/- 0.215 mm to 4.488 +/- 0.163 mm
      (mean +/- SEM, P < 0.05) equivalent to a fractional increase in diameter (fD) of
      1.5 with no significant change in mean arterial pressure, 108 +/- 2 mmHg to 106
      +/- 1 mmHg (mean +/- SEM). The average value of E(inc) per cardiac cycle at
      baseline was 2.17 +/- 0.10 * 10(3) kPa and remained relatively constant until fD
      exceeded 1.3 thereafter increasing to a maximum of 9.23 +/- 1.0 * 10(3) kPa.
      CONCLUSION: These results show that in a conduit artery during the dilatory
      response to shear stress, the interaction between smooth muscle and collagen
      operates so as to maintain E(inc) relatively constant over much of the working
      range of dilatation. This is consistent with a model of the arterial wall in
      which collagen is recruited both by passive stretch, in response to an increase
      in pressure and therefore wall stress, and also by active contraction of smooth
      muscle.

PMID- 21199397
TI  - Regulation of blood flow in the microcirculation: role of conducted vasodilation.
AB  - This review is concerned with understanding how vasodilation initiated from local
      sites in the tissue can spread to encompass multiple branches of the resistance
      vasculature. Within tissues, arteriolar networks control the distribution and
      magnitude of capillary perfusion. Vasodilation arising from the microcirculation
      can 'ascend' into feed arteries that control blood flow into arteriolar networks.
      Thus distal segments of the resistance network signal proximal segments to dilate
      and thereby increase total oxygen supply to parenchymal cells. August Krogh
      proposed that innervation of capillaries provided the mechanism for a spreading
      vasodilatory response. With greater understanding of the ultrastructural
      organization of resistance networks, an alternative explanation has emerged:
      Electrical signalling from cell to cell along the vessel wall through gap
      junctions. Hyperpolarization originates from ion channel activation at the site
      of stimulation with the endothelium serving as the predominant cellular pathway
      for signal conduction along the vessel wall. As hyperpolarization travels, it is
      transmitted into surrounding smooth muscle cells through myoendothelial coupling
      to promote relaxation. Conducted vasodilation (CVD) encompasses greater distances
      than can be explained by passive decay and understanding such behaviour is the
      focus of current research efforts. In the context of athletic performance, the
      ability of vasodilation to ascend into feed arteries is essential to achieving
      peak levels of muscle blood flow. CVD is tempered by sympathetic neuroeffector
      signalling when governing muscle blood flow at rest and during exercise.
      Impairment of conduction during ageing and in diseased states can limit physical
      work capacity by restricting muscle blood flow.

PMID- 21199400
TI  - Effect of pre-breathing oxygen at different depth on oxidative status and calcium
      concentration in lymphocytes of scuba divers.
AB  - AIM: In-water pre-breathing oxygen at various depths reduces decompression
      induced bubble formation and platelet activation, but it could induce side
      effects such as oxidative stress. The aim of this study was to investigate the
      effect of in-water pre-breathing oxygen, at different depths, on the oxidative
      status and intracellular calcium ([Ca(2+) ]i) of peripheral blood lymphocytes
      isolated from six divers. They participated in a 4-diving protocol. Two week
      recovery time was allowed between successive dives. Before diving, all divers,
      for 20 min, breathed normally at sea level (dive 1), 100% oxygen at sea level
      (dive 2), 100% oxygen at 6 msw (dive 3), 100% oxygen at 12 msw (dive 4). Then
      they dived to 30 msw for 20 min with air tank. METHODS: Blood samples were
      collected before and after each dive. Hydrogen peroxide (H(2) O(2) ) levels,
      catalase (CAT) activity, mRNA expression of CAT, glutathione peroxidase (GPx) and
      superoxide dismutase (SOD), and the [Ca(2+) ]i in lymphocytes were measured.
      RESULTS: The dives slightly decreased lymphocyte number and significantly reduced
      lymphocyte H(2) O(2) levels. CAT activity was higher after scuba diving and, dive
      3 enhanced mRNA gene expression of CAT, GPx and SOD. The [Ca(2+) ]i was higher
      after dive 1 and 2 than pre-diving, while was maintained at pre-diving value
      after dive 3 and 4. CONCLUSION: Our results suggest that pre-breathing oxygen, in
      particular at 12 msw, may enhance lymphocyte antioxidant activity and reduce
      reactive oxygen species levels. Pre-breathing oxygen in water may also preserve
      calcium homeostasis, suggesting a protective role in the physiological lymphocyte
      cell functions.

PMID- 21199401
TI  - Preventive dietary potassium supplementation in young salt-sensitive Dahl rats
      attenuates development of salt hypertension by decreasing sympathetic
      vasoconstriction.
AB  - AIM: Increased potassium intake attenuates the development of salt-dependent
      hypertension, but the detailed mechanisms of blood pressure (BP) reduction are
      still unclear. The aims of our study were (i) to elucidate these mechanisms, (ii)
      to compare preventive potassium effects in immature and adult animals and (iii)
      to evaluate the therapeutic effects of dietary potassium supplementation in rats
      with established salt hypertension. METHODS:   Young (4-week-old) and adult (24
      week-old) female salt-sensitive Dahl rats were fed a high-salt diet (5% NaCl) or
      a high-salt diet supplemented with 3% KCl for 5 weeks. The participation of
      vasoconstrictor (renin-angiotensin and sympathetic nervous systems) and
      vasodilator systems [prostanoids, Ca(2+) -activated K(+) channels, nitric oxide
      (NO)] was evaluated using a sequential blockade of these systems. RESULTS:
      Preventive potassium supplementation attenuated the development of severe salt
      hypertension in young rats, whereas it had no effects on BP in adult rats with
      moderate hypertension. Enhanced sympathetic vasoconstriction was responsible for
      salt hypertension in young rats and its attenuation for potassium-induced BP
      reduction. Conversely, neither salt hypertension nor its potassium-induced
      attenuation were associated with significant changes of the vasodilator systems
      studied. The relative deficiency of vasodilator action of NO and Ca(2+) 
      activated K(+) channels in salt hypertensive Dahl rats was not improved by
      potassium supplementation. CONCLUSIONS: The attenuation of enhanced sympathetic
      vasoconstriction is the principal mechanism of antihypertensive action exerted by
      preventive potassium supplementation in immature Dahl rats. Dietary potassium
      supplementation has no preventive effects on BP in adult salt-loaded animals or
      no therapeutic effects on established salt hypertension in young rats.

PMID- 21199399
TI  - Dynamics of muscle microcirculatory and blood-myocyte O(2) flux during
      contractions.
AB  - The O(2) requirements of contracting skeletal muscle may increase 100-fold above
      rest. In 1919, August Krogh's brilliant insights recognized the capillary as the
      principal site for this increased blood-myocyte O(2) flux. Based on the premise
      that most capillaries did not sustain RBC flux at rest, Krogh proposed that
      capillary recruitment [i.e. initiation of red blood cell (RBC) flux in previously
      non-flowing capillaries] increased the capillary surface area available for O(2)
      flux and reduced mean capillary-to-mitochondrial diffusion distances. More modern
      experimental approaches reveal that most muscle capillaries may support RBC flux
      at rest. Thus, rather than contraction-induced capillary recruitment per se,
      increased RBC flux and haematocrit within already-flowing capillaries probably
      elevate perfusive and diffusive O(2) conductances and hence blood-myocyte O(2)
      flux. Additional surface area for O(2) exchange is recruited but, crucially, this
      may occur along the length of already-flowing capillaries (i.e. longitudinal
      recruitment). Today, the capillary is still considered the principal site for
      O(2) and substrate delivery to contracting skeletal muscle. Indeed, the presence
      of very low intramyocyte O(2) partial pressures (PO(2)s) and the absence of
      intramyocyte PO(2) gradients, whilst refuting the relevance of diffusion
      distances, place an even greater importance on capillary hemodynamics. This
      emergent picture calls for a paradigm-shift in our understanding of the function
      of capillaries by de-emphasizing de novo'capillary recruitment'. Diseases such as
      heart failure impair blood-myocyte O(2) flux, in part, by decreasing the
      proportion of RBC-flowing capillaries. Knowledge of capillary function in healthy
      muscle is requisite for identification of pathology and efficient design of
      therapeutic treatments.

PMID- 21199402
TI  - The vascular extracellular calcium-sensing receptor: an update.
AB  - The extracellular calcium-sensing receptor (CaR) was first described in the
      parathyroid gland. Recent studies have shown that the CaR is also expressed in
      blood vessels, especially in the endothelial and adventitial layers but its
      physiological function is still not clear. However, an understanding of its
      possible role(s) in the vasculature (perivascular-neurones, heart and blood
      vessels) is important because of the use of synthetic positive allosteric CaR
      modulators in hyperparathyroidism and the potential importance of negative
      modulators in the treatment of osteoporosis. In this review, the effects of CaR
      activation and inhibition are detailed and the possible role of the CaR as both
      an amplifier and attenuator of myo-endothelial coupling in the vasculature is
      described.

PMID- 21199405
TI  - Global Osteitis Scoring Scale and chronic rhinosinusitis: a marker of revision
      surgery.
AB  - OBJECTIVES: Determine the incidence and severity of osteitis in patients with
      chronic rhinosinusitis using a new Global Osteitis Scoring Scale. DESIGN:
      Validation and prospective case-control study. SETTING: Academic Tertiary
      Otolaryngology Department (Academic Medical Centre, Amsterdam). PARTICIPANTS: A
      prospective series of 102 patients undergoing a computed tomography (CT) sinuses
      as part of their evaluation for chronic rhinosinusitis between January and May
      2008 (study group) and an age- and gender-matched control group of 68 non
      rhinosinusitis patients. Seventy-eight of the chronic rhinosinusitis patients
      completed the nasal subset of the RhinoSinusitis Outcome Measure (RSOM-31) and
      visual analogue scales. Their CT scans were assessed for osteitis using a newly
      developed Global Osteitis Scoring Scale. A subsample of 35 scans were
      additionally scored by a second otolaryngologist and a radiologist. MAIN OUTCOME
      MEASURES: Global Osteitis Scoring Scale. RESULTS: The interrater variability of
      Global Osteitis Scoring Scale was low (average intraclass correlation
      coefficient: 0.94). Forty per cent of the chronic rhinosinusitis group and none
      of the control group had evidence of clinically significant osteitis. In the
      chronic rhinosinusitis group (102 patients), the severity of osteitis was
      correlated with Lund-Mackay (L-M) score (P<0.001), duration of symptoms (P<0.01)
      and previous surgery (P<0.001), rising in incidence with increasing number of
      previous operations. There was no association between osteitis and age, gender,
      smoking, co-existing asthma, allergy or Sumpter's triad. Additionally, there was
      no correlation between osteitis and symptom burden including headache, facial
      pain and nasal subset score of the RhinoSinusitis Outcome Measure. CONCLUSION: In
      patients with recalcitrant chronic rhinosinusitis who have undergone multiple
      surgeries in the past, the incidence of osteitis can be as high as 64%. It does
      not seem to be associated with more troublesome symptoms; however, it is strongly
      associated with previous sinus surgery, which may be a manifestation of a shared
      endpoint (underlying recalcitrant disease).

PMID- 21199406
TI  - Correlation between acoustic rhinometry and subjective nasal patency during nasal
      challenge test in subjects with suspected occupational rhinitis; a prospective
      controlled study.
AB  - OBJECTIVES: To assess the correlation between acoustic rhinometry and visual
      analogue scale endpoints in the context of nasal challenge with occupational
      agents. DESIGN: Prospective controlled study. SETTING: University teaching
      hospital. PARTICIPANTS: Sixty-seven subjects with a history of work-related
      rhinitis and asthma symptoms. MAIN OUTCOMES MEASURES: Subjects underwent nasal
      challenge with control and specific agent on consecutive days. Nasal congestive
      response to challenge was monitored by acoustic rhinometry and visual analogue
      scale. RESULTS: Results showed no correlation between visual analogue scale and
      acoustic rhinometry measurements at baseline on the control (r=-0.13, P=0.3) and
      active (r=0.14, P=0.2) challenge days. No correlation was found between acoustic
      rhinometry and visual analogue scale when analysing all measurements obtained at
      all times after challenge with the control and active agent (control: r=0.09,
      P=0.04; active: r=0.001, P=0.9). The correlation between acoustic rhinometry and
      visual analogue scale was good and significant (r=-0.62, P=<0.01) when the
      analysis was restricted to cases showing a decrease in nasal volume>40% from
      baseline values. CONCLUSIONS: We showed that the correlation between acoustic
      rhinometry and subjective nasal patency was poor on steady conditions. However, a
      significant correlation was observed in those cases showing a greater nasal
      congestive response after challenge measured by acoustic rhinometry.

PMID- 21199407
TI  - Routine calcium measurement is not necessary after most thyroid surgeries: a
      prospective clinical study.
AB  - OBJECTIVES: Calcium levels are often measured to diagnose postoperative
      hypocalcaemia following thyroidectomy. The aims of this study were to (i)
      prospectively determine the incidence of symptomatic and biochemical
      hypocalcaemia following thyroidectomy, (ii) to identify if any associations exist
      between hypocalcaemia, type of surgery, histological diagnosis, specimen
      size/weight and the presence of histological parathyroid tissue and (iii) to
      evaluate the necessity of routine measurement of calcium levels following all
      thyroidectomies. DESIGN: Prospective clinical study. SETTINGS: University
      teaching hospital. PARTICIPANTS: Eighty-six patients presenting consecutively for
      thyroid surgery. OUTCOME MEASURES: Type of surgery, indications, perioperative
      calcium levels, symptoms of hypocalcaemia and histology were documented. RESULTS:
      Fifty-four patients underwent thyroid lobectomy and isthmusectomy, 19 underwent
      total and 13 completion thyroidectomy. Significantly, no patient undergoing
      thyroid lobectomy developed hypocalcaemia versus 26% of total thyroidectomies
      (P=0.001) and 23% of completion thyroidectomies (P=0.006). All eight patients
      with hypocalcaemia required treatment. Seven were initially identified
      clinically. Logistic regression analysis revealed that operation type was the
      only independent risk factor for developing hypocalcaemia (P=0.021). CONCLUSIONS:
      No patient developed hypocalcaemia following thyroid lobectomy and isthmusectomy.
      Considering the majority (63%) of thyroid surgeries were lobectomies, most
      patients tested appear low risk for hypocalcaemia. Definitive prediction of
      hypocalcaemia postoperatively remains a challenge. However, our results suggest
      that analysing calcium levels routinely following thyroid lobectomy is
      unwarranted.

PMID- 21199408
TI  - How good is a chest CT scan at predicting the risk of pulmonary metastatic
      disease in patients with head and neck cancer? A retrospective observational
      study.
AB  - OBJECTIVES: Our objectives were to assess whether a CT chest, when performed as
      part of initial staging investigations, is a robust method to identify lung
      metastases or synchronous primary lung cancers in patients with head and neck
      squamous cell and whether small nodules are likely to represent metastases in
      this group of patients. DESIGN:   Retrospective observational study performed
      between 1994 and 2005. SETTING: Head and neck cancer department, Queen Elizabeth
      Hospital, Birmingham. PARTICIPANTS: All patients that were included had a new
      head and neck squamous cell carcinoma and underwent a CT chest as part of their
      staging investigation. MAIN OUTCOME MEASURES: The presence of lung masses on the
      initial screening CT of the chest as determined by the radiologist's report. The
      development of lung metastases or primary bronchogenic carcinoma in any patient.
      RESULTS: Two hundred and thirty-nine patients met the inclusion criteria. 38
      (16%) patients had a CT chest report for a lung malignancy (either metastatic or
      primary bronchogenic), 33 of these 38 (87%) patients actually had a lung
      malignancy. 32 (13%) patients had a CT chest report for a small nodule, three of
      these 32 (9%) patients were later diagnosed with a lung malignancy, all at a
      different site to the nodule. 169 (71%) patients had normal CT chest reports, of
      these 3 (2%) patients were later diagnosed with a lung malignancy. CONCLUSIONS:
      The CT chest is a useful screening tool but is not infallible. Small nodules
      should be taken seriously and monitored, but should not alter the initial
      decision as to the management of the patient.

PMID- 21199409
TI  - Tracheobronchial foreign body aspiration in children: how reliable are clinical
      and radiological signs in the diagnosis?
AB  - OBJECTIVES: To evaluate the yield of clinical and radiological features in the
      diagnosis of suspected foreign body aspiration in children and to assess factors
      associated with delayed diagnosis of foreign body aspiration. STUDY DESIGN AND
      SETTING: Retrospective review of 10 years of experience in tertiary referral
      centre. PARTICIPANTS: Data were extracted from clinical records of children who
      underwent rigid bronchoscopy for suspected foreign body aspiration at the
      University of Nigeria Teaching Hospital Enugu from 2000 to 2009. MAIN OUTCOME
      MEASURES: Clinical features and radiological findings were validated against
      bronchoscopic findings. RESULTS: Data of 103 children, (mean=2.7 years,
      range=months to 14 years; 64% boys and 36% girls, were analysed. Majority (73%)
      were under 3 years of age. Foreign body aspiration was proven bronchoscopically
      in 85 (83%) patients. The most common symptoms were sudden choking crisis (74%)
      and paroxysms of cough (73%). Independent predictors of proven foreign body
      aspiration were witnessed aspiration, choking crisis and unilateral decreased
      breath sounds in univariate (P=0.001, <0.001, and 0.001 respectively) and
      multivariable analyses (P=0.02, 0.001, and <0.001 respectively). The most
      sensitive and specific clinical features were choking (86%) and witnessed
      aspiration episode (89%), respectively. Available chest radiographs revealed
      radio-opaque objects in 27% of patients. Delayed diagnosis of foreign body
      aspiration (>72 h) was significantly more in younger children (t=3.29; P=0.001),
      as well as in children with no history of witnessed aspiration, negative chest
      examination and radiological signs (P<0.001, P=0.02 and P=0.04 respectively).
      CONCLUSION: To prevent the delayed diagnosis, witnessed aspiration, choking
      crisis, unilateral decreased breath sounds and radiopaque objects should be
      checked in all suspected cases. When history is doubtful, regardless of
      radiological findings, bronchoscopy can be strongly recommended in the presence
      of two factors.

PMID- 21199410
TI  - Coenzyme Q10 in combination with steroid therapy for treatment of sudden
      sensorineural hearing loss: a controlled prospective study.
AB  - OBJECTIVE: To evaluate the therapeutic efficacy of coenzyme Q10 added to systemic
      steroid in patients with idiopathic sudden sensorineural hearing loss. DESIGN: A
      controlled prospective study. SETTING: Asan medical center, University of Ulsan
      College of Medicine. PARTICIPANTS: Between August 2007 and October 2008, the
      first 60 patients diagnosed with sudden sensorineural hearing loss were managed
      with systemic steroid treatment for 2 weeks including 5-day hospitalisation. And
      the second 60 patients were managed with coenzyme Q10 for 2 weeks added to
      previous management. MAIN OUTCOME MEASURES: We evaluated auditory function by
      pure tone audiometry and speech discrimination score. Auditory evaluations were
      performed before and 3 months after treatment using Siegel's criteria. The degree
      of improvement in four-tone average hearing and speech discrimination score was
      calculated from the results before and after treatment. RESULTS: The total
      hearing improvement rate after the treatment was 75.0% (90/120 patients) in this
      study. Although 47 patients (78.3%) of coenzyme Q10 group showed better hearing
      improvement than 43 patients (71.7%) of control group, there was no significant
      difference. However, the coenzyme Q10 group showed significantly higher
      improvement in speech discrimination score. CONCLUSION: From this study, we
      suggest that coenzyme Q10 may have beneficial effects in the treatment of sudden
      sensorineural hearing loss.

PMID- 21199412
TI  - Cochrane review of grommet surgery for OME: 2010.

PMID- 21199414
TI  - Endoscopic vidian neurectomy. An on-line video tutorial: how to do it.

PMID- 21199415
TI  - Appraisal of litigation against English Health Trusts in the treatment of adults
      with ear, nose & throat pathology: how we do it.

PMID- 21199416
TI  - Do printed information leaflets improve recall of the procedure and risks in
      adult tonsillectomy? How we do it.

PMID- 21199417
TI  - A draping method to facilitate intraoperative transnasal flexible laryngoscopy
      during thyroplasty with arytenoid adduction.

PMID- 21199418
TI  - Fibre-optic laryngoscope and endotracheal tube assembly: a robust method of
      monitoring recurrent laryngeal nerve function during thyroid surgery: how we do
      it.

PMID- 21199419
TI  - Flexible laryngoscopy using a trans-oral adaptor.

PMID- 21199420
TI  - Length of stay in hospital for adult tonsillectomy: a prospective study on
      patients' preferences.

PMID- 21199421
TI  - Canine fossa puncture along with endonasal endoscopy for the management of fungal
      balls in the maxillary sinus.

PMID- 21199422
TI  - A physician as a cancer of the neck patient: experiences in the otolaryngology
      ward after laryngectomy.

PMID- 21199423
TI  - Introduction of a new surgical technique: medico-legal aspects.

PMID- 21199425
TI  - Biologic characteristics of bone marrow-derived mesenchymal stem cells from a
      patient with thalassemia syndrome.
AB  - INTRODUCTION: Mesenchymal stem cells (MSCs) are capable of self-renewal and
      differentiating morphologically and functionally into several mesenchymal
      tissues. There have been contrasting data on whether MSCs are altered in various
      hematologic disorders. METHODS: We isolated bone marrow (BM)-derived MSCs from a
      patient with thalassemia syndrome to compare phenotypic and functional
      characteristics to those from normal healthy donor. RESULTS: No differences were
      observed between MSCs from thalassemia syndrome (T-MSCs) and those from normal
      healthy donor in terms of morphology, phenotype, karyotype, multidifferentiation
      capacity. In mixed lymphocyte reaction, T-MSCs strongly inhibited the
      proliferation of allogeneic T cells in association with reduced proportion of
      CD3(+), CD4(+), and CD8(+) cells. Furthermore, the fraction of Treg cells was
      increased under the culture with T-MSCs, suggesting that T-MSCs exert normal
      immunomodulatory function. In addition, T-MSCs expressed hematopoietic cytokines
      and supported hematopoiesis, which was comparable to those from normal BM-derived
      MSCs. CONCLUSION: T-MSCs exhibited normal phenotype, karyotype as well as normal
      immunomodulatory function, and autologous MSCs from patients with thalassemia
      syndrome may be an attractive source of stem cell in terms of hematopoietic
      support as well as immunomodulatory activity.

PMID- 21199426
TI  - Conversion to type 1 diabetes after H1N1 influenza infection: a case report.

PMID- 21199427
TI  - Cross-sectional and longitudinal association of serum alanine aminotransaminase
      and gamma-glutamyltransferase with metabolic syndrome in middle-aged and elderly
      Chinese people.
AB  - BACKGROUND: Although associations of the liver enzymes alanine aminotransaminase
      (ALT) and gamma-glutamyltransferase (GGT) with metabolic syndrome (MetS) are well
      recognized, whether they are independent of insulin resistance and which enzyme
      is more effective are yet to be clarified. METHODS: A total of 5404 subjects aged
      >= 40 years were recruited from two urban communities in Shanghai for cross
      sectional analyses. A subgroup of 681 participants without MetS at baseline was
      included in the longitudinal analyses. Insulin resistance was measured using the
      homeostasis model assessment of insulin resistance (HOMA-IR), and the modified
      National Cholesterol Education Program Adult Treatment Panel III criteria were
      adopted to diagnose MetS. RESULTS: Both GGT and ALT were strongly and positively
      associated with MetS risks in simple and multivariate analyses. Further
      adjustment for HOMA-IR and ALT did not change the association of GGT and MetS
      materially, whereas adjustment for HOMA-IR and GGT substantially attenuated the
      ALT-MetS association. In longitudinal analyses, risks of developing MetS were
      increased across GGT quartiles in a dose-dependent manner after extensive
      adjustments (odds ratios were 1.00, 1.38, 1.62, and 2.29 for GGT, quartile 1
      through quartile 4; P for trend = 0.01). In contrast, ALT was no longer
      associated with MetS development after final adjustment for GGT (P for trend =
      0.09). CONCLUSIONS: Our study confirmed significant and independent associations
      of GGT and ALT with MetS in adult Chinese people. Moreover, GGT might be more
      effective for indicating the future development of MetS.

PMID- 21199428
TI  - Australian & New Zealand Faculty of Radiation Oncology Genito-Urinary Group: 2010
      consensus guidelines for definitive external beam radiotherapy for prostate
      carcinoma.
AB  - External beam radiotherapy for prostate cancer has undergone substantial
      technological and clinical advances in the recent years. The Australian & New
      Zealand Faculty of Radiation Oncology Genito-Urinary Group undertook a process to
      develop consensus clinical practice guidelines for external beam radiotherapy for
      prostate carcinoma delivered with curative intent, aiming to provide guidance for
      clinicians on the appropriate integration of clinical evidence and newer
      technologies. Draft guidelines were presented and discussed at a consensus
      workshop in May 2009 attended by radiation oncologists, radiation therapists and
      medical physicists. Amended guidelines were distributed to radiation oncologists
      in Australia, New Zealand and Singapore for comment, and modifications were
      incorporated where appropriate. Evidence based recommendations for risk
      stratification, the role of image-guided and intensity-modulated radiation
      therapy, prescribed dose, simulation and treatment planning, the role and
      duration of neo-adjuvant/adjuvant androgen deprivation therapy and outcome
      reporting are presented. Central to the guidelines is the recommendation that
      image-guided radiation therapy should be used when definitive external beam
      radiotherapy for prostate cancer is prescribed. The consensus guidelines provide
      a co-operatively developed, evidence-based framework for contemporary treatment
      of prostate cancer with external beam radiotherapy.

PMID- 21199429
TI  - Bone subtraction CT angiography for the detection of intracranial aneurysms.
AB  - INTRODUCTION: The aim of the study was to retrospectively analyse the accuracy of
      CT angiography (CTA) of the Circle of Willis and a prototype bone subtraction CT
      angiogram (BSCTA) compared with digital subtraction angiography (DSA) in the
      detection of intracranial aneurysms. METHODS: A total of 36 patients with
      suspected subarachnoid haemorrhage who had CTA scans that had matching DSA
      studies between November 2005 and December 2006 were retrospectively reviewed by
      two experienced neurointerventionalist. Three-dimensional volume-rendered (3D VR)
      CTA and BSCTA were reviewed, followed by review of the source data in multi
      planar reformats (MPRs). The results were then assessed for sensitivity and
      specificity compared with the gold standard DSA. Time taken to review the
      studies, visibility of the ophthalmic, posterior communicating arteries, superior
      cerebella artery, posterior cerebral artery on the 3D VR BSCTA and CTA were
      analysed. BSCTA was assessed for residual bone and artificial stenosis. Further,
      the aneurysms were analysed for suitability of endovascular treatment versus
      surgical treatment based on CTA and BSCTA with MPR and 3D VR. RESULTS: CTA 3D VR
      sensitivity and specificity was 94 and 80%, respectively. CTA MPR sensitivity and
      specificity was 100% and 90%, respectively. When both CTA 3D VR and MPR images
      were combined the sensitivity and specificity was 100 and 90%, respectively.
      BSCTA 3D VR sensitivity and specificity was 91 and 90%, respectively, and the MPR
      sensitivity and specificity was 97 and 90%, respectively. When both BSCTA 3D VR
      and MPR images were combined the sensitivity was 97% with a specificity of 90%
      Overall, an 84% correlation was found between both CTA and BSCTA when compared
      with DSA for assessing for suitability of endovascular treatment versus surgical
      treatment. A statistically significant difference was shown between the time
      taken to review the CTA and BSCTA (P < 0.001 confidence interval 3.1-3.9 min).
      CONCLUSION: In this study there was no significant difference between the
      diagnostic ability of BSCTA compared with CTA. Importantly, both CTA and BSCTA
      had high sensitivities and specificities compared to DSA.

PMID- 21199430
TI  - Clinical outcomes following endovascular treatment of the malfunctioning
      autologous dialysis fistula.
AB  - BACKGROUND: There is limited long-term prospective data on the use of
      endovascular techniques and the use of thrombolysis in malfunctioning autologous
      haemodialysis fistulas. PURPOSE: Prospective assessment of clinical outcomes
      following angioplasty with or without low-dose thrombolysis was undertaken in
      patients who presented with malfunctioning autologous haemodialysis fistulas.
      METHODS: Consecutive patients referred to our department over a 6-month period
      were included. Twenty-five patients underwent percutaneous intervention by
      angioplasty alone (n = 14), angioplasty and stent (n = 2), thrombolysis alone (n
      = 2), angioplasty, thrombolysis and stent (n = 2) and angioplasty and
      thrombolysis (n = 5). Patients underwent clinical follow-up and were reviewed at
      6, 12, 18 and 24 months to determine fistula status. Thirty-day mortality in the
      group was two patients. Statistical analysis was performed with Mann-Whitney, chi
      squared and Kruskal-Wallis tests. Kaplan-Meier curves were constructed to compare
      primary and secondary patency rates. RESULTS: Technical success and initial
      clinical success rates were 88% and 76%, respectively. Primary and secondary
      clinical success rates at 6 months were 68% and 72%, at 12 months were 68% and
      72%, at 18 months were 60% and 68% and at 24 months were 52% and 68%,
      respectively. There were no major complications following interventional
      procedures. There were four minor complications. After an initially successful
      procedure, five patients required subsequent intervention during the follow-up
      period. The overall fistula event rate was very low (five per 600 patient months
      or 0.0996 per access year) with a fistula loss rate of 0.14 per access year.
      CONCLUSIONS: Our results confirm that excellent clinical results can be achieved
      by percutaneous endovascular treatment in malfunctioning autologous fistulas,
      justifying their continued use as first-line management.

PMID- 21199431
TI  - Corpus callosum: normal imaging appearance, variants and pathologic conditions.
AB  - Various types of lesions can occur within the corpus callosum (CC) which is a
      white matter tract communicating corresponding regions of the cerebral
      hemispheres. Magnetic resonance imaging is the modality of choice for the
      evaluation of the CC. In addition, diffusion weighted imaging and diffusion
      tensor imaging can provide additional information about the CC. The aim of this
      study is to illustrate the imaging features of the corpus callosum and its
      pathologies.

PMID- 21199433
TI  - RE: Why Australian radiology needs Broadband.

PMID- 21199432
TI  - Personal journey on appropriate and quality imaging.

PMID- 21199434
TI  - High-dose fractionated radiotherapy to 80 Gy for stage I-II medically inoperable
      non-small-cell lung cancer.
AB  - INTRODUCTION: Management of medically inoperable non-small-cell lung cancer
      (NSCLC) has been historically challenging, with poor rates of local control and
      disease-specific survival. Nearly all published series of standard fractionation
      radiotherapy have utilised doses <70 Gy. The present investigation describes
      disease control and survival outcomes for a large series of patients prescribed
      high-dose radiotherapy for early-stage NSCLC. METHODS: Retrospective analysis of
      disease control and survival outcomes for stages I-II NSCLC patients prescribed
      >=70 Gy at 1.8-2.5 Gy per fraction. RESULTS: Between May 1997 and August 2008,
      100 primary lung tumours in 98 patients (two metachronous) were eligible for
      analysis. The median age was 71 years (range 49-93), and 92 patients were
      considered medically inoperable. Nearly all cases were clinical stage cT1N0 (51
      patients) or cT2N0 (35). The median radiotherapy dose prescribed was 80.5 Gy
      (range 70-90). At a median follow-up of 18 months, 72 patients died (44 of/with
      disease) and 50 experienced recurrence. The estimated 3-year in-field control,
      progression-free survival, disease-specific, and overall survival rates were 50,
      29, 30 and 24%, respectively. Univariate analyses demonstrated an inverse
      association between local control and tumour size. Medical inoperability was
      associated with decreased disease-specific and overall survivals. Patient age and
      biologically equivalent dose were also associated with overall survival.
      CONCLUSIONS: Disease control and survival of fractionated radiotherapy for early
      stage NSCLC remain suboptimal. Medical inoperability is associated with worse
      overall survival; however, local control remains a predominant pattern of failure
      despite 80 Gy in standard fractionation, particularly in patients with larger
      tumour size.

PMID- 21199435
TI  - The utility of multimodality imaging with CT and MRI in defining rectal tumour
      volumes for radiotherapy treatment planning: a pilot study.
AB  - AIMS: This study compares the volumetric and spatial relationships of gross
      tumour volume (GTV) derived from CT (CT-GTV) and GTV derived from MRI (MR-GTV) to
      determine the utility of multi-modality imaging for radiotherapy treatment
      planning in rectal cancer. METHODS AND MATERIALS: Fifteen patients with T3 rectal
      cancer were accrued over 18 months. The male : female ratio was 2:1. The average
      age was 60.3 years (range 38-79). All patients underwent a diagnostic MRI and CT
      and MRI simulation. Data sets were co-registered. A site specialised diagnostic
      radiologist contoured all volumes in consultation with a radiation oncologist. CT
      GTV was contoured while blinded to MR data sets. MR-GTV was contoured
      independently 2-4 weeks later whilst blinded to its respective CT-GTV data.
      Tumour volumes were analysed for three anatomical subregions (sigmoid, rectal and
      anal). Reference points on tumour volumes were used for spatial comparison and
      analysis. RESULTS: The mean CT-GTV/MR-GTV ratio was 1.2 (range 0.5-2.9). The
      tumour volume ratios for the rectal subregion were well correlated. CT-GTV
      provided adequate spatial coverage of tumour in reference to MR-GTV with the
      average mean discrepancy of 0.12 (range -0.08-0.38) or a maximum discrepancy of
      <0.4 cm (1.54 standard deviation). CT-GTV coverage was inadequate for tumours
      with MRI evidence of anal and sigmoid invasion. CONCLUSIONS: Conventional
      simulation CT imaging provided a reasonable estimate of the GTV. Multi-modality
      imaging with staging MRI can assist target volume definition where there is
      involvement of the sigmoid and anorectal region and avoid geographic misses. The
      role of a simulation MRI may aid in this process but remains investigational.

PMID- 21199436
TI  - Clinician's guide to prostate IMRT plan assessment and optimisation.
AB  - Intensity-modulated radiotherapy (IMRT) offers dosimetric benefit for irregularly
      shaped treatment volumes compared to three-dimensional conformal approaches. Some
      groups advocate IMRT as the standard of care for prostate radiotherapy. For
      clinicians, assessment of an IMRT plan can introduce new opportunities and
      challenges. Although a standard IMRT plan may be deemed acceptable by meeting pre
      set dose constraints, further optimisation may yield a superior treatment plan by
      further reducing dose to critical structures or improving target volume
      homogeneity. The aim of this article is to present aspects of IMRT planning
      relevant to clinicians to aid in plan critiquing.

PMID- 21199443
TI  - Experimental surgical therapies for Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder
      characterized by abnormal movement, cognitive decline, and psychiatric
      disturbance. HD is caused by a trinucleotide repeat expansion in the HTT gene and
      a corresponding neurotoxic polyglutamine expansion in the huntingtin protein.
      There is currently no therapy to modify the progressive course of the disease,
      and symptomatic treatment options are limited. In this review we describe a
      diverse set of emerging experimental therapeutic strategies for HD: deep brain
      stimulation; delivery of neurotrophic factors; cell transplantation; HTT gene
      silencing using RNA interference or antisense oligonucleotides; and delivery of
      intrabodies. The common feature of these experimental therapies is that they all
      require a neurosurgical intervention, either for implantation of an electrode or
      for brain delivery of molecules, viruses or cells that do not cross the blood
      brain barrier upon oral or intravenous administration. We summarize available
      data on the rationale, safety, efficacy, and intrinsic limitations of each of
      these approaches, focusing mainly on studies in HD patients and genetic animal
      models of HD. Although each of these strategies holds significant promise, their
      efficacy remains to be proven in HD patients.

PMID- 21199444
TI  - Parkinson's disease dementia and potential therapeutic strategies.
AB  - Dementia in Parkinson's disease (PD-D) has only been acknowledged in the recent
      three decades, but research in this field has accelerated. The purpose of this
      review was to discuss advances in PD-D regarding biomarker correlates and
      potential therapeutic targets. Attention and executive dysfunction, memory
      deficits that improve with cueing, and visual hallucinations are characteristic
      in PD-D. PD-D dramatically increases the disability and misery of the disease.
      Current treatment for PD-D is symptomatic, modest, and only transiently
      effective. There is wide agreement that more effective treatment is needed, but
      this will require more knowledge about PD-D pathophysiology. Advances in the
      pathogenesis of PD have focused on the substantia nigra, which is the location
      from where the pathophysiology of motor symptoms primarily arises in initial
      stages. In contradistinction, pathology studies have suggested that cognitive
      decline correlates with cortical and subcortical-cortical projection pathway
      abnormalities. There is evidence that substantia nigra mechanisms, including
      protein aggregation of alpha-synuclein (e.g., Lewy bodies) may also play a role
      in cortical neuron degeneration. Other different mechanisms, such as Alzheimer's
      disease pathology (e.g., Abeta aggregation) may be operant for PD-D. Biomarkers
      of various types are being proposed for the study of PD-D as well as for
      objective measures of PD-D prediction and progression. Therapeutic targets are
      currently derived mostly from general PD neurodegeneration research rather than
      cortical PD neurodegeneration per se. Protein aggregation, genes that are
      associated with PD, oxidative stress, inflammation, and trophic factors
      constitute the major classes of therapeutic targets for PD-D. More research is
      needed on the specific aspects of cortical dysfunction and degeneration that
      create PD-D.

PMID- 21199445
TI  - Neuropsychiatric aspects of schizophrenia.
AB  - Cognitive and affective deficits are prominent clinical features of schizophrenia
      that impact functioning and are a challenge to effective treatment. The
      integration of functional magnetic resonance imaging (fMRI) with cognitive and
      affective neuroscience paradigms enables examination of the brain systems
      underlying domain-specific behavioral deficits manifested in schizophrenia. There
      has been a marked increase in the number of studies that apply fMRI in
      neurobiological studies of schizophrenia. This article highlights phenotypic
      features of schizophrenia that emerge from these studies and provides a
      neuropsychiatric perspective. Such efforts have helped elucidate potential neural
      substrates of deficits in cognition and affect in schizophrenia by providing
      measures of activation to neurobehavioral probes and connectivity among brain
      regions. Studies have demonstrated abnormalities at early stages of sensory
      processing that may influence downstream abnormalities in more complex evaluative
      functioning. The methodology can help bridge integration with neuropharmacologic,
      genomic, and neurorehabilitation investigations.

PMID- 21199447
TI  - Dysfunctional brain networks and genetic risk for schizophrenia: specific
      neurotransmitter systems.
AB  - Multiple neurotransmitter circuits are disturbed in schizophrenia, and the
      dopamine hypothesis of schizophrenia prevails as the hypothesis with most
      empirical support. On the other hand, schizophrenia is highly heritable with a
      pattern consistent with both common and rare allelic variants and gene *
      environment interaction. Advances in the field of neuroimaging have expanded our
      knowledge of intermediate phenotypes, the neurobiological processes that convey
      the risk from the genes to the complex phenotype. In this article, we review the
      recent and continuously accumulating evidence from in vivo imaging studies aiming
      at characterizing neurochemical intermediate phenotypes of schizophrenia.
      Dopaminergic alterations in schizophrenia are shared by individuals at genetic
      risk who do not express the illness, suggesting a "dopamine hypothesis of
      schizophrenia vulnerability." This hypothesis has the potential to help us better
      understand the dopaminergic dysfunction in the context of the complex
      pathophysiological process leading to schizophrenia. In the future,
      neurotransmitter imaging studies should investigate the gene * environment
      interaction in schizophrenia, and try to identify neurobiological correlates of
      heightened sensitivity to environmental stressors (e.g., cannabis, childhood
      trauma, and other psychosocial stress) in genetically vulnerable individuals.

PMID- 21199446
TI  - The upside of APP at synapses.
AB  - The memory dysfunctions that characterize Alzheimer's disease (AD) are strongly
      correlated with synapse loss. The amyloid precursor protein (APP) and its
      cleavage product Abeta play central roles in synapse and memory loss, and thus
      are strongly implicated in the pathogenesis of AD. Numerous in vitro and
      transgenic AD mouse model studies have shown that overexpression of APP leads to
      Abeta accumulation, which causes decreased synaptic activity and dendritic spine
      density. However, the normal synaptic function of APP itself is not fully
      understood. Several recent studies have found that full-length APP promotes
      synaptic activity, synapse formation, and dendritic spine formation. These
      findings cast APP as a potential key player in learning and memory. It is of
      interest that the synaptic functions of full-length APP are opposite to the
      effects associated with pathological Abeta accumulation. In this review, we will
      summarize the normal functions of APP at synapses and spines along with other
      known functions of APP, including its role in cell motility, neuronal migration,
      and neurite outgrowth. These studies shed light on the physiological actions of
      APP, independent of Abeta effects, and thus lead to a better understanding of the
      synaptic dysfunctions associated with AD.

PMID- 21199450
TI  - Revisiting the diagnosis of schizophrenia: where have we been and where are we
      going?
AB  - Appropriate and reliable classification of mental illness is crucial for
      advancing the field of psychiatry as agreement on diagnosis has broad
      implications for treatment of mental disorders and research into the
      etiopathophysiology of mental disorders. Since schizophrenia was first recognized
      by Kraepelin (as dementia praecox), there has been much discussion about what
      does and does not diagnostically constitute the disorder. The importance placed
      upon different symptoms and course types associated with schizophrenia has been
      as heterogeneous as the disorder itself. This article focuses upon the
      classification of schizophrenia over the last 100 years, the current diagnosis of
      schizophrenia, changes for schizophrenia planned in the upcoming DSM 5, future
      directions for improving the diagnosis of schizophrenia, and the implications of
      a new diagnostic paradigm for the illness.

PMID- 21199448
TI  - Description of study population and analysis of factors influencing adherence in
      the observational Italian study "Evaluation of Pharmacotherapy Adherence in
      Bipolar Disorder" (EPHAR).
AB  - BACKGROUND: In patients with bipolar disorder, medication is effective in
      preventing relapses. Unfortunately, adherence to treatment in bipolar disorder,
      as in other chronic or recurrent conditions, is not optimal. Estimates of
      nonadherence to prescribed treatment range from 30% to 60% in epidemiological
      studies, and are at around 30% in clinical trials. Adherence to treatment is a
      potent predictor of effectiveness, both in clinical trials and cohort studies,
      therefore is a very relevant area of investigation. This study will try to show a
      picture of the real life care where adherence is influenced by a wide range of
      variables. METHODS: Prospective, observational, multicenter study in 650 adult
      patients with bipolar disorder, who had to initiate or change their treatment
      regimen, observed for 1 year. Adherence was measured by the Simplified Medication
      Adherence Questionnaire (SMAQ). Additional variables: Symptom severity,
      Montgomery-Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale
      (YMRS), Clinical Global Impression-Bipolar Disorder (CGI-BD), the Drug Attitude
      Inventory score (DAI-30), and quality of life (EuroQoL 5 Dimensions). The
      variables were recorded every 3 months for the next year. RESULTS: Most subjects
      were out-patients (77.1%), female (58.8%), aged 31-50 years (50.1%) and
      overweight (41.8%) or obese (28.7%); 67.4% had type I bipolar disorder and 66.8%
      had depressive or mixed symptoms. Adherence was 39.9% at baseline (and increased
      up to 67.0% at completion. The main predictors of nonadherence were alcohol
      consumption, severe bipolar symptoms, young age at time of first treatment,
      negative attitude towards treatment. CONCLUSIONS: The patient population of this
      observational trial was representative of the patients changing their therapy for
      bipolar disorder seen in clinical practice in Italy. Lack of adherence to
      pharmacotherapy for bipolar disorder is a serious issue, which is more likely to
      arise in alcohol users and patients with severe symptoms, negative attitude
      towards medication and/or initiation of treatment early in life. The findings
      could lead to a more adequate approach of adherence in patients with bipolar
      disorders.

PMID- 21199451
TI  - Presynaptic dopamine in schizophrenia.
AB  - Presynaptic dopamine (DA) transmission has been measured in schizophrenia using
      different paradigms aimed at providing estimates of the integrity or the activity
      of the presynaptic dopaminergic neuron. RESEARCHERS HAVE MEASURED: (1) DA
      synthesis capacity with [(18) F]DOPA, a measure of the activity of dopa
      decarboxylase, (2) DA release with studies measuring the impact of a DA releasing
      stimulant challenge on the binding of a D(2) receptor radiotracer, (3) D(2)
      baseline occupancy by DA, a measure of baseline intrasynaptic DA, assessed by the
      changes in binding of D(2) radiotracer induced by DA depletion, and (4) the DA
      and the vesicular monoamine transporters, to assess the integrity of presynaptic
      terminals. The relationship between DA release and D(2) receptor occupancy at
      baseline by DA has also been assessed in the same patients. Overall, these
      different imaging modalities have converged to show a dysregulation of
      presynaptic dopaminergic activity in schizophrenia, leading to excessive DA
      release in the striatum, particularly in the projection to the associative
      striatum, an area of integration between cognitive and limbic cortical inputs.
      Excessive striatal presynaptic DA is linked to the emergence of acute psychotic
      symptoms and to their response to treatment in schizophrenia. Understanding the
      etiology of this dysregulation and its consequences on the rest of the circuitry
      is important for future drug development.

PMID- 21199449
TI  - Dopamine receptor homooligomers and heterooligomers in schizophrenia.
AB  - Over the past two decades the dopamine D2 receptor has been undoubtedly the most
      widely studied dopamine receptor for the therapeutic treatment of schizophrenia,
      as the majority of antipsychotics exhibit antagonism at this receptor. However,
      the cognitive symptoms of the disorder are mostly resistant to the majority of
      available antipsychotic treatments and, as a result, there is a critical need to
      develop novel therapies that ameliorate all symptoms. The recognition that
      dopamine receptors, such as all G protein-coupled receptors (GPCRs), exist as
      oligomeric complexes has provided new avenues for drug design in the search for
      novel therapies. Furthermore, that it is now known that dopamine receptors can
      form heteromers, such as the dopamine D1-D2 receptor heteromer, with pharmacology
      and function distinct from its constituent receptors, has significantly expanded
      the range of potential drug targets. The aim of this review is to discuss the
      therapeutic relevance of these dopamine receptor oligomers to schizophrenia and
      to address the potential value of dopamine receptor heteromers in the search for
      new therapeutic strategies.

PMID- 21199452
TI  - Clioquinol: review of its mechanisms of action and clinical uses in
      neurodegenerative disorders.
AB  - Clioquinol was produced as a topical antiseptic and marketed as an oral
      intestinal amebicide in 1934, being used to treat a wide range of intestinal
      diseases. In the early 1970s, it was withdrawn from the market as an oral agent
      because of its association with subacute myelo-optic neuropathy (SMON), a
      syndrome that involves sensory and motor disturbances in the lower limbs and
      visual changes. The first methods for determining plasma and tissue clioquinol (5
      chloro-7-iodo-8-quinolinol) levels were set up in the 1970s and involved HPLC
      separation with UV detection, these were followed by a more sensitive GC method
      with electron capture detection and a gaschromatographic-massspectrometric (GC
      MS) method. Finally, an HPLC method using electrochemical detection has proved to
      be as highly sensitive and specific as the GC-MS. In rats, mice, rabbits, and
      hamsters, clioquinol is rapidily absorbed and undergoes first-pass metabolization
      to glucuronate and sulfate conjugates; the concentrations of the metabolites are
      higher than those of free clioquinol. Bioavailabilty versus intraperitoneal
      dosing is about 12%. Dogs and monkeys form fewer conjugates. In man, single-dose
      concentrations are dose related, and the drug's half-life is 11-14 h. There is no
      accumulation, and the drug is much less metabolized to conjugates. Clioquinol
      acts as a zinc and copper chelator. Metal chelation is a potential therapeutic
      strategy for Alzheimer's disease (AD) because zinc and copper are involved in the
      deposition and stabilization of amyloid plaques, and chelating agents can
      dissolve amyloid deposits in vitro and in vivo. In general, the ability of
      clioquinol to chelate and redistribute metals plays an important role in diseases
      characterised by Zn, Cu, Fe dyshomeostasis, such as AD and Parkinson's disease,
      as it reduces oxidation and the amyloid burden. Zinc chelators may also act as
      anticancer agents. Animal toxicity studies have revealed species-specific
      differences in neurotoxic responses that are related to the serum levels of
      clioquinol and metabolites. This is also true in humans, who form fewer
      conjugates. The results of studies of Alzheimer patients are conflicting and need
      further confirmation. The potential therapeutic role of the two main effects of
      MPACs (the regulation of the distribution of metals and antioxidants) has not yet
      been fully explored.

PMID- 21199454
TI  - Unsuspected multiple myeloma presenting as Escherichia coli infectious
      spondylitis: a case report.
AB  - Multiple myeloma associated with infectious spondylitis at initial presentation
      is rare. We report a previously healthy woman with back pain for 3 weeks,
      initially diagnosed as Escherichia coli infectious spondylitis. Because magnetic
      resonance imaging revealed skip lesions other than infectious spondylitis,
      extensive work-up disclosed monoclonal immunoglobulin G kappa and 30% plasma
      cells in bone marrow. The patient was treated with antibiotics for 8 weeks
      without recurrence in the subsequent 6 months. Although the panorama of
      infectious spondylitis was obvious and substantial, our case demonstrates that
      further investigations for underlying diseases are critical, especially when
      image findings are incompatible with common presentations of infectious
      spondylitis.

PMID- 21199453
TI  - Diagnosis of Paget's disease of the pelvis using F-18 FDG PET/CT.
AB  - Sclerotic lesions of the right iliac bone were discovered incidentally in a 52
      year-old Korean woman. In this case, imaging of the right iliac bone showed
      intense osteoblastic activity on the bone scan and very mild F-18-fluoro-2
      deoxyglucose (FDG) uptake on positron emission tomography (PET). Since Paget's
      disease is rare in Koreans, we aimed to rule out other bone diseases such as
      osteoblastic metastasis or osteomyelitis. These results allowed us to exclude
      chronic osteomyelitis or malignancy and clarify the diagnosis of Paget's disease
      of the iliac bone. This case illustrates how F-18 FDG PET/CT can be a useful tool
      in the differential diagnosis of various bone diseases.

PMID- 21199455
TI  - Utilisation of plasma exchange in the treatment of digital infarcts in Wegener's
      granulomatosis.
AB  - Digital ischemia is a rare manifestation of Wegener's granulomatosis (WG) with
      previous management approaches based on the hypotheses of thromboembolic
      phenomenon and vasospasm. WG is an autoimmune, antineutrophil cytoplasmic
      antibody-predominant small-to-medium-vessel necrotising vasculitis which mainly
      affects the pulmonary-renal system. We report on a patient with WG presenting
      with digital infarction. We successfully treated this patient who had digital
      infarcts refractory to cyclophosphamide, steroids and vasodilator agents, with
      plasma exchange.

PMID- 21199456
TI  - The autoimmunity conundrum: clotting or inflammation.
AB  - Antiphospholipid syndrome (APS) is an autoimmune condition with a myriad of
      clinical manifestations ranging from cardiovascular, neurologic, renal
      involvement to cutaneous manifestations and thrombocytopenia. We describe a young
      woman who presented with fever, cough and dyspnea. She had a history of recurrent
      pregnancy losses and her antiphospholipid antibodies and lupus serologies were
      positive. Echocardiography showed mobile mitral and aortic valve vegetations. She
      was treated as for infective endocarditis and diagnosed with primary APS with
      lupus-like disease. Vigilance is required to establish if there is an underlying
      rheumatological condition in a patient who presents with presumptive infective
      endocarditis in the absence of risk factors. Treatment for systemic lupus
      erythematosus and primary APS are distinct.

PMID- 21199457
TI  - Exacerbation of adult-onset Still's disease, possibly related to elevation of
      serum tumor necrosis factor-alpha after etanercept administration.
AB  - Adult-onset Still's disease (AOSD) is a systemic inflammatory disease of unknown
      etiology. A 44-year-old male patient presented with AOSD complicated by
      macrophage activation syndrome after etanercept therapy. His serum tumor necrosis
      factor-alpha (TNF-alpha) level was increased dramatically after etanercept
      therapy. The clinical course of this case suggests that the increased TNF-alpha
      level by etanercept administration might cause macrophage activation syndrome in
      this case.

PMID- 21199458
TI  - IgG4-related retroperitoneal fibrosis: the first reported case in a Chinese
      population.
AB  - Immunoglobulin G4 (IgG4)-related sclerosing disease is a newly recognized
      clinicopathological entity characterized by lymphoplasmacytic infiltration and
      varying degrees of fibrosis in various organs, with abundant IgG4-positive plasma
      cells in tissues. Patients usually exhibit multisystem involvement and often
      respond well to steroid and immunosuppressive therapy. However, this disease has
      been rarely reported in a Chinese population. We herein report a case of IgG4
      related sclerosing disease solely presenting with retroperitoneal fibrosis that
      was effectively treated with systemic steroid therapy. To the best of our
      knowledge, this is the first reported case of IgG4-related retroperitoneal
      fibrosis in a Chinese population.

PMID- 21199459
TI  - Intramedullary fat necrosis, polyarthritis and panniculitis with pancreatic
      tumor: a case report.
AB  - Acute polyarthritis can occur in non-rheumatic systemic illnesses, presenting a
      diagnostic dilemma. We present an extremely rare case presenting as acute
      polyarthritis, panniculitis and medullary fat necrosis with underlying pancreatic
      pathology. This case report describes a young woman presenting with panniculits,
      pancreatic tumour, polyarthritis and intra-osseus fat necrosis with a fatal
      outcome. The medical fraternity needs to be aware of this potentially fatal
      albeit rare musculoskeletal complication secondary to a pancreatic pathology.

PMID- 21199460
TI  - Systemic lupus erythematosus complicated with posterior reversible encephalopathy
      syndrome and intracranial vasculopathy.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic condition
      characterized by reversible vasogenic edema on neuroimaging. It is associated
      with various neurological manifestations, including headaches, vomiting,
      seizures, visual loss, altered mental status and focal neurological deficits.
      PRES mainly occurs in the setting of eclampsia, hypertension, uremia, malignancy,
      transplantation, autoimmune diseases and/or use of immunosuppressive drugs. This
      syndrome has been described in patients with systemic lupus erythematosus (SLE).
      PRES is a potentially reversible clinical-radiological entity; however, it can be
      complicated with vasculopathy, infarction or hemorrhage. Vasculopathy has been
      demonstrated to be a common finding in patients with SLE. We report the case of a
      woman with lupus nephritis and PRES whose diffuse vasculopathy was present on
      initial neuroimaging. Subsequent brain computed tomography scan demonstrated
      interval development of intraparenchymal hemorrhage and subarachnoid hemorrhage.
      To our knowledge, this unique brain image pattern has not been reported in SLE
      patients.

PMID- 21199461
TI  - Subcutaneous methotrexate is well tolerated and superior to oral methotrexate in
      the treatment of rheumatoid arthritis.

PMID- 21199462
TI  - Citrullinated peptide and its relevance to rheumatoid arthritis: an update.
AB  - Citrullinated peptides in autoimmune diseases have been extensively studied in
      the last two decades. It is suggested that citrullination and the anti
      citrullinated peptide antibodies (ACPA) plays a critical role in initiating
      inflammatory responses in autoimmune diseases, such as rheumatoid arthritis (RA).
      The most commonly accepted molecular mechanism for citrullinated
      peptides/proteins in RA is that the modified antigen resulting from cell damage
      or uncontrolled apoptosis could evoke an immune response leading to
      autoantibodies against these peptide or the whole protein. Citrullination of
      arginine is catalyzed by the enzyme peptidylarginine-deiminase (PAD) in the
      presence of calcium, changing the positively charged arginine to a polar but
      neutral citrulline. These citrullinated peptides/proteins and the relevant
      antibodies (ACPA) are important, not only in initiation of RA, but also in the
      diagnosis of the disease. In this evidence-based clinical review, we summarize
      recently published data on peptide citrullination and ACPA gauging the ability of
      anti-cyclic citrullinated peptide (anti-CCP) antibodies for diagnosis of RA. We
      also recapitulate results of studies elucidating the mechanism underlying the
      disease.

PMID- 21199463
TI  - Low-dose and high-dose methotrexate are two different drugs in practical terms.
AB  - Methotrexate (MTX) was originally synthesised as an anti-cancer drug. Soon it was
      also used in immunoinflammatory diseases, mainly in the field of rheumatology.
      However, the dose used in oncology is several-fold higher as compared to the dose
      used in systemic immunoinflammatory rheumatological diseases. This led to the use
      of terms 'low-dose MTX' (LD-MTX) and 'high-dose MTX' (HD-MTX) respectively for
      its use in immunoinflammatory rheumatological diseases as against its use in
      oncology. Extensive studies have demonstrated that therapeutic action, clinical
      indications, adverse effects and mechanisms of action of LD-MTX and HD-MTX are
      quite different. It is somewhat akin to low-dose aspirin versus high-dose aspirin
      with entirely different spectra of therapeutic action and adverse effects. It is
      important to understand this difference. This would help in allaying unfounded
      fear of adverse effects of LD-MTX that is often mistakenly considered the same as
      that of HD-MTX used in oncology.

PMID- 21199464
TI  - How to critically appraise and apply meta-analyses in clinical practice.
AB  - AIM: Prompted by a clinical question, we critically appraised a meta-analysis of
      efficacy and safety of mycophenolate mofetil (MMF) versus cyclophosphamide (CYC)
      in the treatment of proliferative lupus nephritis. METHODS: Systemic reviews and
      a meta-analysis are introduced to the reader in the perspective of a clinical
      scenario that raises questions about applicability of certain treatment options
      in clinical practice. Critical appraisal of meta-analysis addresses three
      questions. (i) What are the results? (ii) Are the results valid? (iii) How can I
      apply the results to my patient care? RESULTS: A meta-analysis paper titled
      'Mycophenolate mofetil is as efficacious as, but safer than, cyclophosphamide in
      the treatment of proliferative lupus nephritis: a meta-analysis and meta
      regression'by Mak et al. (2009) was selected. Our critical appraisal identified
      several strengths of the paper, such as having a clearly focused clinical
      question, considering clinically important outcomes, using appropriate inclusion
      criteria to select primary studies, assessing quality of selected papers, good
      reproducibility in the assessment of primary studies and performing sensitivity
      analysis and meta-regression to account for heterogeneity. Nevertheless, we also
      identified several weaknesses, such as possibly missing out other relevant
      studies, possible selection bias, low quality of some primary studies used and
      lack of data on cost effectiveness. CONCLUSION: Meta-analyses have an important
      role in the implementation of evidence-based practice and shaping of future
      research. Despite the undoubted advantages, meta-analyses are no panacea.
      Caution, therefore, has to be applied when using the results of meta-analyses in
      clinical practice, due to methodological limitations of the meta-analyses and
      limitations in the primary studies used.

PMID- 21199465
TI  - Psoriatic arthritis: a systematic review.
AB  - Psoriatic arthritis is an inflammatory rheumatic disorder of unknown etiology
      occurring in patients with psoriasis. The Classification Criteria for Psoriatic
      Arthritis study group has recently developed a validated set of classification
      criteria for psoriatic arthritis with a sensitivity of 91.4% and a specificity of
      98.7%. Three main clinical patterns have been identified: oligoarticular (<= 4
      involved joints) or polyarticular (>= 5 involved joints) peripheral disease and
      axial disease with or without associated peripheral arthritis. In this context
      distal interphalangeal arthritis and arthritis mutilans may occur. According to
      other reports, also in our centre, asymmetric oligoarthritis is the most frequent
      pattern at onset. Axial disease has been estimated between 5% and 36% of
      patients. It is characterized by an irregular involvement of the axial skeleton
      with a predilection for the cervical spine. Recurrent episodes of enthesitis and
      dactylitis represent a hallmark of psoriatic arthritis. In around 20% of cases
      distal extremity swelling with pitting edema of the hands or feet is observed.
      Unilateral acute iridocyclitis, usually recurrent in alternate fashion, is the
      most frequent extra-articular manifestation, and accelerated atherosclerosis is
      the prominent comorbidity. The clinical course of peripheral and axial psoriatic
      arthritis is usually less severe than rheumatoid arthritis and ankylosing
      spondylitis, respectively. Local corticosteroid injections and non-steroidal anti
      inflammatory drugs are recommended in milder forms. Sulphasalazine and
      methotrexate are effective in peripheral psoriatic arthritis. Recent studies have
      provided evidence on the efficacy of anti-tumor necrosis factor-alpha drugs to
      control symptoms and to slow or arrest radiological disease progression.

PMID- 21199466
TI  - Vitamin D deficiency: the time to ignore it has passed.
AB  - It is true to say that it is just over the past decade and even more so in this
      new decade that it has become appreciated how vitally important vitamin D is for
      optimum health. This 'sunshine' vitamin could justifiably be called 'the nutrient
      of this decade'. Until recently, vitamin D was known primarily for its role in
      bone health. However, as a result of advances in research this perspective has
      changed. While it is true to say that the classic function of vitamin D is to
      control calcium and vitamin D metabolism, we now know that the importance of
      vitamin D spreads far wider than just bone health. There is much ongoing research
      with regard to its emerging role in immunopathology, as a potent inhibitor of
      cellular growth, stimulator of insulin secretion, modulator of immune function
      and inhibitor of renin production. This review discusses the current evidence
      with regard to the clinical consequences of vitamin D deficiency and underscores
      the fact that physicians should be vigilant in searching for and treating this
      preventable and treatable condition. Furthermore, this review highlights the fact
      that the time is opportune for rheumatologists to agree upon clinical guidelines
      to advise practitioners as to when and in which patients to check for, what
      target vitamin D level to aim for and how best to treat vitamin D deficiency.

PMID- 21199467
TI  - Psychosocial interventions as adjunct therapy for patients with rheumatoid
      arthritis: a systematic review.
AB  - AIM: To identify the psychological interventions for which there is consistent,
      high quality evidence of efficacy in the treatment of patients with rheumatoid
      arthritis (RA). METHOD: A computer-aided search and manual screening of
      identified papers was conducted. Randomised controlled trials published in
      English in peer-reviewed journals, assessing the use of psychological
      interventions in adult patients with RA were included. RESULTS: Thirty-four
      papers published between 1981 and 2009 encompassing 31 studies with 2021 patients
      were included. There is consistent supportive evidence for the efficacy of
      disclosure therapy (four studies) and cognitive behavioural therapy (CBT) with
      maintenance therapy (five studies). There is supportive evidence for improvement
      with CBT of greater than 6 weeks duration (six studies) in the short-term but
      conflicting evidence for its long-term efficacy. There is some evidence for
      improvement with biofeedback-based interventions (two studies). There is
      conflicting evidence for the benefits of counselling (three studies),
      psychotherapy (two studies) mindfulness and meditation (two studies), and CBT of
      less than 6 weeks duration (six studies). There is limited evidence regarding
      relaxation therapy (two studies). Methodological limitations of the reviewed
      literature included failure of allocation concealment, blinding and conduction of
      intention-to-treat analysis, as well as the heterogeneity and choice of outcome
      measures. CONCLUSIONS: This review shows consistent supportive evidence for the
      use of disclosure therapy, and CBT with maintenance therapy as adjunct therapies
      in patients with RA. It also highlights methodological limitations in the current
      literature and the need for future research in this area.

PMID- 21199468
TI  - Diagnostic value of anti-modified citrullinated vimentin in rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid factors (RF) are currently used in the diagnosis of
      rheumatoid arthritis (RA). Several other autoantibodies found in RA are directed
      to epitopes in citrullinated proteins such as anti-cyclic citrullinated and
      recently anti-modified citrullinated vimentin (MCV). OBJECTIVE: In this study we
      determined the sensitivity and specificity of anti-MCV in comparison with anti
      cyclic citrullinated peptide (CCP) antibodies and RF in RA patients and in a
      control group using the American College of Rheumatology (ACR) criteria as the
      gold standard. MATERIALS AND METHODS: A cross sectional study was conducted from
      January to December 2008 on 100 patients with RA and 153 patients with arthritis
      or arthralgia but not fulfilling ACR criteria for RA. Serum from each subject was
      tested for anti-MCV, anti-CCP antibodies and immunoglobulin G (IgG) RF by enzyme
      linked immunosorbent assay. Sensitivity and specificity of the tests were
      evaluated using the ACR criteria as the gold standard. RESULTS: The sensitivity
      of RF was 85% with 74.5% specificity. For anti-CCP antibodies the sensitivity was
      71% and the specificity was 94.8%. The sensitivity of anti-MCV antibodies was 80%
      with 59.5% specificity. The area under the curve for RF was 0.759, for anti-CCP
      antibodies was 0.866 and for anti-MCV antibodies was 0.681, while for at least
      one positive test it was 0.691. CONCLUSION: Anti-CCP antibodies have higher
      diagnostic specificity and positive predictive value than RF and anti-MCV
      antibodies. RF has the highest sensitivity when compared to anti-CCP and anti-MCV
      antibodies. Thus anti-MCV antibody is not a better marker when compared to RF or
      anti-MCV antibody in the diagnosis of RA patients.

PMID- 21199469
TI  - Association between nonspecific skeletal pain and vitamin D deficiency.
AB  - BACKGROUND: Deficiency of vitamin D has been reported in patients with many types
      of musculoskeletal pain. The present study was designed to determine the
      association between serum 25-hydroxyvitamin D [25-(OH)D] deficiency and
      nonspecific skeletal pain. METHODS: A total of 276 patients with nonspecific
      skeletal pain at different regions of the skeletal system diagnosed as leg pain,
      widespread pain, arthralgia, rib pain, back pain and fibromyalgia were compared
      with 202 matched controls with regard to mean serum 25-(OH)D level and 25-(OH)D
      deficiency. Serum 25-(OH)D was measured by enzyme-linked immunosorbent assay
      method and levels < 20 ng/mL were considered as deficient. Nonparametric one-way
      analysis of variance, Kruskal Wallis and Wilcoxon tests were used for group
      comparisons. Multiple logistic regression analysis with calculation of adjusted
      odds ratio (OR) and 95% confidence interval (95% CI) were performed to determine
      associations. RESULTS: In patients with nonspecific skeletal pain the mean 25
      (OH)D was significantly lower (P = 0.0001) and the proportion of 25-(OH)D
      deficiency was significantly higher (63.4%vs. 36.1%, P = 0.0001) compared with
      controls. There was a significantly positive association between 25-(OH)D
      deficiency and skeletal pain (OR = 2.94, 95% CI = 1.01-4.3, P = 0.0001). The
      strength of association varied across the groups with strongest association
      observed with leg pain (OR = 7.4; 95% CI = 3.9-13.9, P = 0.0001) followed by
      arthralgia (OR = 3.9, 95% CI = 2.1-7.1, P = 0.0001) and widespread pain (OR =
      2.8, 95% CI = 1.1-6.6, P = 0.020) but no association with back pain and
      fibromyalgia. There was a greater positive associations in women compared with
      men (OR = 2.1, 95% CI = 1.1-4.3, P = 0.001). CONCLUSION: The results of this
      study indicate a positive association of vitamin D deficiency with a variety of
      nonspecific bone pain, particularly in women. More studies with larger samples
      are required to confirm these findings. Increasing serum vitamin D to sufficient
      levels and longitudinal follow-up of patients may provide further evidence in
      relation to vitamin D deficiency and skeletal pain.

PMID- 21199470
TI  - Development, implementation and benefits of a rheumatology-specific electronic
      medical record application with automated display of outcome measures.
AB  - OBJECTIVES: To make a rheumatology-specific electronic medical record (EMR)
      application for easy clinical data entry, automated display of outcome measures
      in real-time that generates well laid-out print-outs; and provides an easily
      retrievable database for clinical analysis and research. METHODS: Highly labour
      intensive 'MS-WORD ' template used earlier provided the basic framework for
      developing rheumatology-EMR applications. The authors, a rheumatologist and a
      soft tissue surgeon with expertise in developing medical software, successfully
      created a rheumatology-EMR application over a period of 21/2 years using the same
      basic flow of work as used in the old 'MS-WORD ' template. RESULTS: The resulting
      EMR application form has a standard medical record documenting demographic data,
      complete diagnosis, appropriate dates, visit number, disease status, history,
      physical examination, investigations, follow-up and prescription page (with
      automatic updates wherever applicable). Mathematical calculations required for
      outcome measures (DAS, DAS28, CDAI, SDAI, AS-DAS, BASDAI, BASFI, BASMI, SLE-DAI
      and others) are embedded in the software, with automated updating as the
      examination of the musculoskeletal system proceeds in real time. Following
      implementation of this EMR application, more patients are being seen, patient
      waiting lists have been reduced; more time is available for academic and teaching
      work, without compromising the quality of notes, and print-outs for patients.
      Data retrieval has simplified clinical research with increased numbers of
      abstracts being presented and research papers being published. CONCLUSION:
      Healthcare workers with understanding of the basic principles of computers and
      softwares should interact with software engineers who are either themselves
      medical doctors or are familiar with the workflow and clinical evaluation
      processes to create an efficient speciality-specific EMR application.

PMID- 21199471
TI  - The ankylosing spondylitis quality of life questionnaire: validation in a New
      Zealand cohort.
AB  - AIM: To examine the validity of the Ankylosing Spondylitis Quality of Life
      Questionnaire (ASQoL) in a New Zealand population with defined axial
      spondyloarthritis (SpA). Once validated, the ASQoL will be included as an outcome
      measure in a proposed multicentre New Zealand study. METHODS: Five healthy
      participants were interviewed to identify any issues related to local dialect or
      linguistic comprehension of the questionnaire. Cognitive debriefing interviews
      were conducted with four participants with SpA to assess the relevance and
      comprehensiveness of the questionnaire. Internal consistency was established by
      determining the Cronbach's alpha. Finally, convergent validity of the ASQoL was
      assessed by testing the correlation with the Bath Ankylosing Spondylitis
      Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index
      (BASDAI) and patient global visual analogue scale (VAS) scores in a cohort of 63
      SpA patients. RESULTS: The language used in the ASQoL was considered clear,
      comprehensible and accessible to speakers of New Zealand English. The
      questionnaire displayed content validity for patients with SpA. The ASQoL had
      good internal consistency in the present sample (alpha = 0.854). A positive
      correlation was found between the ASQoL and the BASFI (rho = 0.635, P < 0.001),
      BASDAI (rho = 0.521, P < 0.001) and patient global assessment VAS (rho = 0.546, P
      < 0.001), providing evidence that the ASQoL has convergent validity among
      patients with SpA in New Zealand. Test-retest reliability was good over 16 weeks
      (rho = 0.730, P < 0.001). CONCLUSIONS: The ASQoL has been demonstrated in this
      study to be feasible, internally consistent and to have content and convergent
      validity in a New Zealand population of patients with axial spondyloarthritis; it
      is a measure of quality of life which is both easy to employ and reliable.

PMID- 21199472
TI  - Behcet's disease in Iran: analysis of 6500 cases.
AB  - OBJECTIVE: To identify the clinical picture of Behcet's disease in a large cohort
      of patients (6500) in Iran, over a period of 35 years, and compare them with
      other large series from around the world. METHODS: Patients with Behcet's disease
      from all over Iran were seen in the Behcet's Disease Research Unit by a
      multidisciplinary team (rheumatologists, dermatologists, and ophthalmologists).
      Diagnosis was based on 'expert opinion'. Data were collected on a standardized
      data sheet (105 items), and stored in an electronic database. Data were updated
      at each follow-up. RESULTS: Male to female ratio was 1.22 :  .00. The mean age at
      onset was 26 years +/- 11.3. The frequency of symptoms were: oral aphthosis
      97.3%, genital aphthosis 64.6%, skin manifestations 64.9% (pseudofolliculitis
      54.5%, erythema nodosum 22.5%, other lesions 7%), pathergy phenomenon 52.5%,
      ophthalmologic manifes-tations 56.8% (anterior uveitis 41.2%, posterior uveitis
      44.9%, retinal vasculitis 32.1%), joint manifestations 37.4% (arthralgia 17.2%,
      monoarticular arthritis 7.6%, oligoarthritis 16.8%, ankylosing spondylitis 2%),
      neurological manifestations 3.8% (central manifestations 3.5%, mononeuritis
      multiplex 0.3%), gastrointestinal manifestations 7.4%, vascular involvement 8.3%
      (phlebitis 5.7%, superficial phlebitis 2.2%, large vein thrombosis 1.1%, arterial
      thrombosis 0.154%, aneurysm 0.5%), epididymitis 4.7%, cardiac involvement 0.6%,
      and pulmonary involvement 0.9%. Sedimentation rate was normal in 46.5% of
      patients. Abnormal urine sediment was detected in 12.2%. HLA-B5 was present in
      53.3% and HLA-B51 in 47.9% of patients. CONCLUSION: Behcet's disease is mainly
      seen in young people. The most frequent symptoms are mucocutaneous, ocular and
      joint manifestations. Comparison with large series did not show major
      differences.

PMID- 21199473
TI  - Systemic lupus erythematosus in Iran: a study of 2280 patients over 33 years.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) as a chronic autoimmune disease has
      a worldwide distribution. There is a wide variation in the natural history of SLE
      among different ethnic and geographic groups. The aim of this study was to show
      the manifestations of SLE in Iranian patients. METHODS: The study was on
      manifestations of SLE according to the database of the Rheumatology Research
      Center (RRC), Tehran, Iran, on registered patients during the period of 1976 to
      2009. RESULTS: A total of 2280 SLE patients (2052 female and 228 male) were
      studied. The female : male ratio was 9 : 1 and the mean age at presentation was
      24.4 +/- 10.4 years. Prevalence of manifestations included: musculoskeletal
      (83.2%), cutaneous (81.1%), renal (65.4%), neuropsychiatric (23.4%), pulmonary
      (21.5%), cardiac (17.2%), and hematologic (66.4%) symptoms. There was positive
      antinuclear antibodies in 86.4% and anti-DNA in 82.3% of patients. Overlap
      syndrome and positive family history with other autoimmune diseases were detected
      in 7.6% and 3.4% of patients, respectively. CONCLUSION: In our patients the
      prevalence of cutaneous involvement was similar to those of nearby countries
      (with similar climate). Renal involvement was seen more than some other countries
      especially more than European countries, while other manifestations (such as
      hematologic and joint involvement) were similar to European countries (with
      similar ethnicity). We may conclude that genetic and/or climatic factors may lead
      to different presentations of lupus.

PMID- 21199474
TI  - Prevalence of rheumatoid arthritis in the eastern Black Sea region of Turkey.
AB  - AIM: The aim of this study was to estimate the prevalence of rheumatoid arthritis
      (RA) in the eastern Black Sea region of Turkey. METHOD: The study was carried out
      between March 2003 and March 2005 by the Karadeniz Technical University Medical
      Faculty Department of Physical Medicine and Rehabilitation in the urban area in
      the eastern Black Sea region of Turkey, which has a population of 459021
      (according to the 2000 national census). A total of 6103 subjects, 20 years old
      or over, were selected by the sampling method; 3023 (49.5%) women and 3080
      (50.5%) men were included in the study. The diagnosis of RA was performed based
      on fulfilling the American College of Rheumatology (ACR) criteria. RESULTS: Fifty
      nine patients were diagnosed with RA according to the ACR criteria, of which 11
      were male and 48 female. The prevalence of RA was 1% (95% CI: 0.75-1.25) in the
      general population, 1.6% (95% CI: 1.15-2.05) in women and 0.35% (95% CI: 0.14
      0.56) in men. The female/male ratio was 4.3 : 1.0, showing that RA prevalence was
      statistically significantly higher in women (P <0.005). CONCLUSION: Our study
      demonstrates that RA is a common disease in Turkish society.

PMID- 21199475
TI  - Prevalence and predictors of osteoporosis in an urban Sri Lankan population.
AB  - AIM: To determine the prevalence of osteoporosis in both women and men and to
      determine the association between osteoporosis and selected risk factors among a
      sample of urban Sri Lankan adults. METHODS: The population aged 35-64 years
      residing in 22 Grama Niladhari divisions, the smallest administrative units in
      the country, of the Medical Officer of Health area Ragama, Sri Lanka, was
      identified using the electoral list and stratified into three age groups (n =
      3012). A random sample was obtained from each stratum and selected individuals
      were invited to participate in the study (n = 1100). A structured, interviewer
      administered questionnaire was used to collect information on demographic data
      and details of risk factors. Bone mineral density (BMD) was measured using a
      peripheral dual-energy X-ray absorptiometry (DEXA) scan in 700 subjects (64%). A
      BMD < -2.5 was considered as osteoporosis. Although peripheral DEXA is less
      sensitive and specific compared to central DEXA it was used in this study as it
      is less costly and easily transportable. RESULTS: Of the 700 subjects who
      consented to participate in the study, 60% (n = 421) were females. In subjects <
      50 years, 9% of women and 3% of men had osteoporosis. In subjects >= 50 years,
      27% of women and 7% of men had osteoporosis. Female sex (odds ratio [OR] 12.0),
      smoking (OR 5.5), age > 50 years (OR 3.1), low BMI (OR 3.1) and low level of
      education (OR 1.7) were positively associated with osteoporosis. CONCLUSIONS:
      Female sex, age, BMI, smoking and level of education were significant predictors
      of osteoporosis. The prevalence of osteoporosis increased in both women and men
      after 50 years.

PMID- 21199476
TI  - Case series of pediatric systemic lupus erythematosus from Kerala: comparison
      with other Indian series.
AB  - AIM: To determine the clinical and laboratory characteristics of patients
      diagnosed with pediatric systemic lupus erythematosus (pSLE) in the general
      pediatrics department of a tertiary level hospital in southern India and compare
      them to data of case series from other parts of the country. METHODS:
      Retrospective chart review by two independent reviewers. All patients diagnosed
      with SLE in the pediatrics department of the Amrita Institute of Medical Sciences
      hospital between 1 January 2004 and 31 September 2008, were included in the
      study. RESULTS: Twenty children were diagnosed with pSLE in the above-mentioned
      period (female : male ratio 2.3 : 1.0). Fever (75% of patients) and arthralgia
      (65%) were the most common clinical presenting features. Many patients who were
      referred as 'Fever of unknown origin' (37.5%) or 'idiopathic thrombocytopenic
      purpura' (15%) fulfilled the diagnosis of SLE on detailed evaluation. Renal
      manifestations were present in 11 patients, seven of whom underwent a biopsy.
      Class IV lupus nephritis was the most common finding (4/7). A very high
      percentage of our patients had hypocomplementemia (85%). The statistical
      significance of the differences between our cohort and previously reported
      cohorts could not be determined. CONCLUSIONS: pSLE patients in our series,
      compared to previous literature from India had a much higher incidence of fever,
      thrombocytopenia and hypocomplementemia at presentation and much lower incidence
      of arthritis. It is unclear whether these differences represent unique
      characteristics of ethnically dissimilar subsets of the Indian population. A high
      index of suspicion should be maintained in order to make an early diagnosis of
      pSLE, since the most common presenting features in our cohort were arthralgia and
      fever.

PMID- 21199477
TI  - Therapeutic effects of astragalus polysaccharides on inflammation and synovial
      apoptosis in rats with adjuvant-induced arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA), an autoimmune disease, is characterized by
      pronounced inflammation and cell accumulation within affected joints. Beneficial
      effects of active ingredients of the astragalus root (Radix astrogali) in
      treatment of immunological diseases have been previously observed, but the
      mechanisms are not well understood. This study aims to evaluate therapeutic
      effects and the mechanisms of astragalus polysaccharides (APS) on adjuvant
      induced arthritis (AA) in rats. METHODS: Effects of treatment of AA rats with
      increasing doses of APS, Tripterygium glycosides (positive control) and saline
      (negative control) on swelling, arthritic index, synovial cell accumulation,
      serum concentrations of tumor necrosis factor alpha (TNF-alpha) and interleukin
      1beta (IL-1beta), synovial apoptosis and immunostaining for Bcl-2 and Bax were
      determined. RESULTS: APS treatment reduced cell accumulation, swelling and
      arthritic index of the joints and serum concentrations of TNF-alpha and IL1-beta
      in a dose-dependent manner in AA rats. Synovial cell apoptosis was elevated in
      response to APS treatment and accompanied by increased staining for pro-apoptotic
      Bax protein and decreased staining for anti-apoptotic Bcl-2 protein. CONCLUSIONS:
      APS treatment reduced multiple indices of arthritis in rats with AA. Results
      support further investigation of therapeutic effects of APS in treatment of RA
      and other autoimmune diseases.

PMID- 21199478
TI  - Serum levels of IL-1beta, IL-6 and TNF-alpha in rats fed with Kashin-Beck disease
      affected diet.
AB  - AIM: To investigate the serum level of interleukin (IL)-1beta, IL-6 and tumor
      necrosis factor (TNF)-alpha in rats which have been fed with Kashin-Beck disease
      (KBD) epidemic district food. METHOD: Two hundred and twenty Wistar rats were
      divided into five groups. Group A was fed with a normal diet as control; group B
      was fed with a normal diet and T-2 toxin; group C was fed with a low-nutrition
      diet and T-2 toxin; group D was fed with a low-nutrition diet; and group E was
      fed with a KBD-affected diet. The serum bioactivity of IL-1beta, IL-6 and TNF
      alpha were tested by enzyme-linked immeunosorbent assay. RESULTS: After 4 weeks,
      the epiphyseal plate showed more obvious necrosis of chondrocytes in groups B, C
      and E. Among the KBD-affected feed, normal feed combined with T-2 toxin and low
      protein combined with T-2 toxin, KBD-affected feed rats had the highest serum
      levels, and normal feed combined with T-2 toxin group was the lowest. Although
      the IL-1beta, IL-6 and TNF-alpha levels were no different in the KBD-affected
      feed compared to low protein combined with T-2 toxin, there were significant
      differences compared to normal feed combined with the T-2 toxin (P < 0.05).
      CONCLUSIONS: Serum levels of IL-1beta, IL-6 and TNF-alpha metabolism are altered
      in the KBD model rats. This effect is relatively similar to the low-nutrition
      diet combined with the T-2 toxin, which means low-nutrition diet may be involved
      in the aetiology of KBD.

PMID- 21199481
TI  - Fear of failure and student athletes' interpersonal antisocial behaviour in
      education and sport.
AB  - BACKGROUND. The link between fear of failure and students' antisocial behaviour
      has received scant research attention despite associations between fear of
      failure, hostility, and aggression. Also, the effect of sport experience on
      antisocial behaviour has not been considered outside of the sport context in
      adult populations. Further, to date, sex differences have not been considered in
      fear of failure research. AIMS. To examine whether (a) fear of failure and sport
      experience predict antisocial behaviour in the university and sport contexts in
      student athletes, and whether this prediction is the same in males and females;
      and (b) sex differences exist in antisocial behaviour and fear of failure.
      SAMPLE. British university student athletes (n= 176 male; n= 155 female; M(age) =
      20.11 years). METHOD. Participants completed questionnaires assessing fear of
      failure, sport experience, and antisocial behaviour in both contexts. RESULTS.
      (a) Fear of failure and sport experience positively predicted antisocial
      behaviour in university and sport and the strength of these predictions did not
      differ between males and females; (b) females reported higher levels of fear of
      devaluing one's self-estimate than males whereas males reported higher levels of
      fear of important others losing interest than females. Males engaged more
      frequently than females in antisocial behaviour in both contexts. CONCLUSIONS.
      Fear of failure and sport experience may be important considerations when trying
      to understand antisocial behaviour in student athletes in education and sport;
      moreover, the potential effect of overall fear of failure and of sport experience
      on this frequency does not differ by sex. The findings make an important
      contribution to the fear of failure and morality literatures.

PMID- 21199482
TI  - Can we predict mathematical learning disabilities from symbolic and non-symbolic
      comparison tasks in kindergarten? Findings from a longitudinal study.
AB  - BACKGROUND: The ability to compare numbers, as the most basic form of number
      sense, has been related to arithmetical achievement. AIMS: The current study
      addressed the predictive value of non-symbolic and symbolic (number word (NW) and
      Arabic number (AN)) comparison for arithmetics by means of a longitudinal design.
      SAMPLE: Sixteen children with mathematical disabilities (MD), 64 low achievers
      (LA), and 315 typical achieving (TA) children were followed from kindergarten
      till grade 2. METHOD: The association of comparison skills with arithmetical
      skills in grades l and 2 was studied. The performances of MD, LA and TA children
      were compared. RESULTS: Regression analyses showed that non-symbolic skills in
      kindergarten were predictively related to arithmetical achievement 1 year later
      and fact retrieval 2 years later. AN comparison was predictively related to
      procedural calculation 2 years later. In grade 2, there was an association
      between both symbolic tasks and arithmetical achievement. Children with MD
      already had deficits in non-symbolic and symbolic AN comparison in kindergarten,
      whereas in grade 2 the deficits in processing symbolic information remained.
      CONCLUSIONS: The combination of non-symbolic and symbolic deficits represents a
      risk of developing MD.

PMID- 21199483
TI  - Cognitive processes in university learning: a developmental framework using
      structural equation modelling.
AB  - BACKGROUND. Both achievement goals and study processing strategies theories have
      been shown to contribute to the prediction of students' academic performance.
      Existing research studies (Fenollar, Roman, & Cuestas, 2007; Liem, Lau, & Nie,
      2008; Simons, Dewitte, & Lens, 2004) amalgamating these two theoretical
      orientations in different causal models have reported their associations with
      other adaptive strategies and motivational constructs - for example, effort
      expenditure. Despite this recognition, there have been to date very few studies
      that explored the relations between achievement goals, study processing
      strategies, effort, and academic performance over time. AIM OF STUDY. The primary
      focus of our study is to explore the relations between the aforementioned
      theoretical constructs over a 2-year period. Specifically, we tested an empirical
      model that conceptualized the relations between performance-approach and mastery
      goals, deep processing strategies, effort, and academic performance across six
      time points of data collection. METHODOLOGY. Two hundred and eighty-one (161
      females, 120 males) university students took part in this study. The participants
      were administered various Likert-scale inventories and the overall course mark
      and final examination were used as indexes of academic performance. RESULTS.
      Structural equation modelling indicated a relatively good fit to the a posteriori
      model and the hypothesized paths were, in part, supported. The major findings
      included the predictive effects of performance-approach goals at Time 1 on deep
      processing strategies at Time 2 and mastery goals at Time 3; the predictive
      effect of mastery goals at Time 3 on effort at Time 4; the predictive effects of
      deep processing at Time 2 on mastery goals at Time 3 and Time 4. Furthermore, the
      placement of deep processing and effort in this structural model also accentuated
      the performance-approach goals - mastery goals - effort - academic performance
      relation, and the performance-approach goals - deep processing - mastery goals -
      effort - academic performance relation. DISCUSSION. Our study has important
      theoretical and practical implications concerning the conceptualization of the
      performance-approach and mastery goals relationship, and the use of goal
      structure and adaptive strategies (e.g., deep processing) to enhance academic
      learning.

PMID- 21199484
TI  - Prevention of school bullying: the important role of autonomy-supportive teaching
      and internalization of pro-social values.
AB  - BACKGROUND: This study examined students' perceptions of autonomy-supportive
      teaching (AST) and its relations to internalization of pro-social values and
      bullying in class. AIMS: We hypothesized that: (1) teachers' AST, which involves
      provision of rationale and taking the student's perspective, would relate
      positively to students' identified internalization of considerateness towards
      classmates, and would relate negatively to external regulation (considerateness
      to obtain rewards or avoid punishments); (2) students' identified regulation
      would relate negatively to self-reported bullying in class, whereas external
      regulation would relate positively to bullying; and (3) the relation between
      teachers' AST and student bullying would be mediated by students' identification
      with the value of considerateness towards others. SAMPLE: The sample consisted of
      725 junior high school students (50% females) in Grades 7 and 8 from 27 classes
      in four schools serving students from lower-middle to middle-class socioeconomic
      backgrounds. METHOD:   The participants completed questionnaires assessing the
      variables of interest. RESULTS: Correlational analysis supported the hypotheses.
      Moreover, mediational analyses using hierarchical linear modelling (HLM)
      demonstrated that identified regulation mediates the negative relation between
      AST and self-reported bullying in class. The mediational hypothesis was supported
      at the between-class level and at the within-class level. CONCLUSIONS:   The
      findings suggest that school policy aimed at bullying reduction should go beyond
      external control that involves external rewards and sanctions and should help
      teachers acquire autonomy-supportive practices focusing on students' meaningful
      internalization.

PMID- 21199485
TI  - The contribution of personality traits and self-efficacy beliefs to academic
      achievement: a longitudinal study.
AB  - BACKGROUND. The personal determinants of academic achievement and success have
      captured the attention of many scholars for the last decades. Among other
      factors, personality traits and self-efficacy beliefs have proved to be important
      predictors of academic achievement. AIMS. The present study examines the unique
      contribution and the pathways through which traits (i.e., openness and
      conscientiousness) and academic self-efficacy beliefs are conducive to academic
      achievement at the end of junior and senior high school. SAMPLE. Participants
      were 412 Italian students, 196 boys and 216 girls, ranging in age from 13 to 19
      years. METHODS. The hypothesized relations among the variables were tested within
      the framework of structural equation model. RESULTS AND CONCLUSIONS. Openness and
      academic self-efficacy at the age of 13 contributed to junior high-school grades,
      after controlling for socio-economic status (SES). Junior high-school grades
      contribute to academic self-efficacy beliefs at the age of 16, which in turn
      contributed to high-school grades, over and above the effects of SES and prior
      academic achievement. In accordance with the posited hypothesis, academic self
      efficacy beliefs partially mediated the contribution of traits to later academic
      achievement. In particular, conscientiousness at the age of 13 affected high
      school grades indirectly, through its effect on academic self-efficacy beliefs at
      the age of 16. These findings have broad implications for interventions aimed to
      enhance children's academic pursuits. Whereas personality traits represent stable
      individual characteristics that mostly derive from individual genetic endowment,
      social cognitive theory provides guidelines for enhancing students' efficacy to
      regulate their learning activities.

PMID- 21199486
TI  - Teachers' use of fear appeals in the mathematics classroom: worrying or
      motivating students?
AB  - AIM. This study examined whether teachers' use of fear appeals in the classroom,
      attempts to motivate students to perform well in high-stakes examinations by
      highlighting the educational, and/or occupational consequences of failure did
      indeed motivate students or whether it contributed to an increase in worry,
      anxiety, and fear of failure. SAMPLE. A total of 132 secondary school students.
      METHOD. Self-report data were collected for teachers' use of fear appeals, test
      anxiety, and achievement goals in the context of Mathematics at the end of Years
      10 and 11, the final 2 years of compulsory schooling. RESULTS. The frequency with
      which teachers were reported to make fear appeals was unrelated to future test
      anxiety and achievement goals. When fear appeals were perceived to be
      threatening, however, they were related to an increase in the worry and tension
      components of test anxiety and increases in performance-avoidance and mastery
      approach goals. CONCLUSION. Fear appeals appear to have competing positive and
      negative outcomes, resulting in both anxiety and a fear of failure, and a mastery
      approach goal.

PMID- 21199487
TI  - Dynamic testing with tangible electronics: measuring children's change in
      strategy use with a series completion task.
AB  - AIMS: This study sought to explore the use of a novel approach that incorporates
      dynamic testing and tangible electronics in the assessment of children's learning
      potential and strategy use. SAMPLE: A total of 77 children with a mean age 8.9
      years participated in the study; half of them were dynamically tested using
      graduate prompt techniques; the others served as a control group. METHOD:
      Children in the experimental group received a series of inputs consisting of a
      pre-test, two training sessions, and a post-test all involving a number of series
      completion tasks; the controls received only pre- and post-tests. All test
      sessions were undertaken individually using a specially designed programme
      incorporating an electronic console and tangible materials equipped internally
      with sensors. RESULTS: As a consequence of training, children significantly
      outperformed controls on a number of series completion tasks. Significant
      individual differences were noted in terms of the children's response to
      assistance. The study's hypothesis that dynamic testing would increase
      analytical, and reduce trial-and-error, behaviour was supported. While a
      significant proportion of the children employed strategies that had earlier been
      identified as optimal, a sizeable minority demonstrated rather more idiosyncratic
      approaches. CONCLUSIONS: Findings from the study demonstrate the potential value
      of electronic dynamic testing using graduated prompts. However, a number of
      further refinements to improve the procedure are suggested.

PMID- 21199488
TI  - Effects of a 'learn to think' intervention programme on primary school students.
AB  - BACKGROUND: Methods for teaching thinking may be described as out-of-context or
      infusion. Both approaches have potential to raise students' general cognitive
      processing ability and so raise academic achievement, but each has disadvantages.
      AIMS: To describe and evaluate a theory-based learn to think (LTT) curriculum for
      primary school students, which draws on the strengths of both out-of-context and
      infusion approaches. SAMPLE: One-hundred and sixty-six students in three classes
      of Grade 1 (6+ years old), Grade 2 (7+ years old), and Grade 3 (8+ years old) in
      a primary school in Shanxi province, China, randomly ascribed to experimental
      (90) and control (76) groups. METHODS: All students were pre-tested for non
      verbal intelligence and academic achievement. Experimental students followed the
      LTT curriculum (one activity every 2 weeks) for 4 school years. All were post
      tested on three occasions for thinking ability and four times for academic
      achievement. RESULTS: Grade 1 and Grade 2 students showed effects of LTT from 1
      year after their start and increasing: on thinking ability d= .78-1.45; on
      Chinese d= .68-1.07; on maths .58-.87. Grade 3 students showed effects from 6
      months after their start: on thinking ability .90-1.37; Chinese .77-1.32; maths
      .65-1.29. The effects were concentrated in students in the middle band of initial
      ability. CONCLUSIONS: A curriculum for teaching thinking based on a structured
      theoretical model that combines elements of out-of-context and infusion methods
      has been shown to have long-term far transfer effects on students' thinking
      ability and academic achievement. More work is needed to meet the needs of a
      wider range of abilities.

PMID- 21199489
TI  - Self-regulated learning of basic arithmetic skills: a longitudinal study.
AB  - BACKGROUND: Several studies have examined young primary school children's use of
      strategies when solving simple addition and subtraction problems. Most of these
      studies have investigated students' strategy use as if they were isolated
      processes. To date, we have little knowledge about how math strategies in young
      students are related to other important aspects in self-regulated learning. AIM:
      The main purpose of this study was to examine relations between young primary
      school children's basic mathematical skills and their use of math strategies,
      their metacognitive competence and motivational beliefs, and to investigate how
      students with basic mathematics skills at various levels differ in respect to the
      different self-regulation components. SAMPLE: The participants were comprised of
      27 Year 2 students, all from the same class. METHOD: The data were collected in
      three stages (autumn Year 2, spring Year 2, and autumn Year 3). The children's
      arithmetic skills were measured by age relevant tests, while strategy use,
      metacognitive competence, and motivational beliefs were assessed through
      individual interviews. The participants were divided into three performance
      groups; very good students, good students, and not-so-good students. RESULTS:
      Analyses revealed that young primary school children at different levels of basic
      mathematics skill may differ in several important aspects of self-regulated
      learning. Analyses revealed that a good performance in addition and subtraction
      was related not only to the children's use of advanced mathematics strategies,
      but also to domain-specific metacognitive competence, ability attribution for
      success, effort attribution for failure, and high perceived self-efficacy when
      using specific strategies. CONCLUSIONS: The results indicate that instructional
      efforts to facilitate self-regulated learning of basic arithmetic skills should
      address cognitive, metacognitive, and motivational aspects of self-regulation.
      This is particularly important for low-performing students.

PMID- 21199490
TI  - Trait emotional intelligence influences on academic achievement and school
      behaviour.
AB  - BACKGROUND. Trait emotional intelligence (trait EI or trait emotional self
      efficacy) refers to individuals' emotion-related self-perceptions (Petrides,
      Furnham, & Mavroveli, 2007). The children's trait EI sampling domain provides
      comprehensive coverage of their affective personality. Preliminary evidence shows
      that the construct has important implications for children's psychological and
      behavioural adjustment. AIMS. This study investigates the associations between
      trait EI and school outcomes, such as performance in reading, writing, and maths,
      peer-rated behaviour and social competence, and self-reported bullying behaviours
      in a sample of primary school children. It also examines whether trait EI scores
      differentiate between children with and without special educational needs (SEN).
      SAMPLE. The sample comprised 565 children (274 boys and 286 girls) between the
      ages of 7 and 12 (M((age)) = 9.12 years, SD= 1.27 years) attending three English
      state primary schools. METHOD. Pupils completed the Trait Emotional Intelligence
      Questionnaire-Child Form (TEIQue-CF), the Guess Who peer assessment, the Peer
      Victimization Scale, and the Bullying Behaviour Scale. Additional data on
      achievement and SEN were collected from the school archives. RESULTS. As
      predicted by trait EI theory, associations between trait EI and academic
      achievement were modest and limited to Year 3 children. Higher trait EI scores
      were related to more nominations from peers for prosocial behaviours and fewer
      nominations for antisocial behaviour as well as lower scores on self-reported
      bulling behaviours. Furthermore, SEN students scored lower on trait EI compared
      to students without SEN. CONCLUSIONS. Trait EI holds important and multifaceted
      implications for the socialization of primary schoolchildren.

PMID- 21199491
TI  - Breast cancer after bilateral risk-reducing mastectomy.
AB  - This study aims to evaluate the incidence of breast cancer after risk-reducing
      mastectomy (RRM) in healthy BRCA mutation carriers. This study is a long-term
      follow-up of 307 BRCA mutation carriers of whom 96 chose RRM. None of the study
      participants had a previous history of breast or ovarian cancer nor had they
      undergone RRM or risk-reducing bilateral salpingo-oophorectomy (BSO) prior to the
      time of BRCA testing. The annual incidence of post-mastectomy breast cancer was
      0.8% compared with 1.7% in the non-operated group. Implications of these findings
      in relation to genetic counseling and future management are discussed.

PMID- 21199492
TI  - Telomere length measurement can distinguish pathogenic from non-pathogenic
      variants in the shelterin component, TIN2.
AB  - Dyskeratosis congenita (DC) is a heterogeneous bone marrow failure syndrome with
      seven disease-causing genes identified to date, six of which are linked to
      telomere maintenance. Mutations in one of these genes (TINF2), which encodes a
      component of the shelterin complex, are associated with particularly short
      telomeres. Among the 224 consecutive patients with different forms of bone marrow
      failure (46 with DC, 122 with aplastic anaemia and 57 with some features of DC),
      we have identified 16 new families with variants in exon 6 of the TINF2 gene,
      eight of which are novel. We observe that the phenotype associated with these
      mutations extends to a severe early presentation, not always classified as DC. In
      addition, we see that some of the variants identified are not associated with
      short telomeres and are also found in asymptomatic individuals. In the absence of
      any direct functional assay, the data indicates that the telomere length
      measurement can inform us as to which variants in TINF2 are pathogenic and which
      may be non-pathogenic.

PMID- 21199493
TI  - Mutations in NMDA receptors influence neurodevelopmental disorders causing
      epilepsy and intellectual disability.

PMID- 21199494
TI  - Disturbances in endocannabinoid metabolism causes autosomal recessive
      neurodegeneration.

PMID- 21199495
TI  - Mutations in a novel cilia-centrosome protein cause a cystic kidney disease
      associated with retinal degeneration.

PMID- 21199496
TI  - Drawing the line: drawing and construction strategies for simple and complex
      figures in Williams syndrome and typical development.
AB  - In the typical population, a series of drawing strategies have been outlined,
      which progressively emerge during childhood. Individuals with Williams syndrome
      (WS), a rare genetic disorder, produce drawings that lack cohesion, yet drawing
      strategies in this group have hitherto not been investigated. In this study, WS
      and typically developing (TD) groups drew and constructed (from pre-drawn lines
      and shapes) a series of intersecting and embedded figures. Participants with WS
      made use of the same strategies as the TD group for simple intersecting figures,
      though were less likely to use a typical strategy for more complex figures that
      contained many spatial relations. When replicating embedded shapes, the WS group
      used typical drawing strategies less frequently than the TD group, despite
      attempting to initiate a strategy that is observed in TD children. Results
      suggested that individuals with WS show a particular difficulty with replicating
      figures that include multiple spatial relations. The impact of figure complexity
      and task demands on performance are discussed.

PMID- 21199497
TI  - Gender differences in online and offline self-disclosure in pre-adolescence and
      adolescence.
AB  - Although there is developmental research on the prevalence of offline self
      disclosure in pre-adolescence and adolescence, it is still unknown (a) how boys'
      and girls'online self-disclosure develops in this period and (b) how online and
      offline self-disclosure interact with each other. We formulated three hypotheses
      to explain the possible interaction between online and offline self-disclosure:
      the displacement, the rich-get-richer, and the rehearsal hypothesis. We surveyed
      690 pre-adolescents and adolescents (10-17 years) at three time points with half
      year intervals in between. We found significant gender differences in the
      developmental trajectories of self-disclosure. For girls, both online and offline
      self-disclosure increased sharply during pre- (10-11 years) and early adolescence
      (12-13 years), and then stabilized in middle and late adolescence. For boys, the
      same trajectory was found although the increase in self-disclosure started 2
      years later. We found most support for the rehearsal hypothesis: Both boys and
      girls seemed to use online self-disclosure to rehearse offline self-disclosure
      skills. This particularly held for boys in early adolescence who typically have
      difficulty disclosing themselves offline.

PMID- 21199498
TI  - Gender differences in the pathway from adverse life events to adolescent
      emotional and behavioural problems via negative cognitive errors.
AB  - The aim of this study was to test for gender differences in how negative
      cognitive errors (overgeneralizing, catastrophizing, selective abstraction, and
      personalizing) mediate the association between adverse life events and
      adolescents' emotional and behavioural problems (measured with the Strengths and
      Difficulties Questionnaire). The sample consisted of 202 boys and 227 girls (aged
      11-15 years) from three state secondary schools in disadvantaged areas in one
      county in the South East of England. Control variables were age, ethnicity,
      special educational needs, exclusion history, family structure, family socio
      economic disadvantage, and verbal cognitive ability. Adverse life events were
      measured with Tiet et al.'s (1998) Adverse Life Events Scale. For both genders,
      we assumed a pathway from adverse life events to emotional and behavioural
      problems via cognitive errors. We found no gender differences in life adversity,
      cognitive errors, total difficulties, peer problems, or hyperactivity. In both
      boys and girls, even after adjustment for controls, cognitive errors were related
      to total difficulties and emotional symptoms, and life adversity was related to
      total difficulties and conduct problems. The life adversity/conduct problems
      association was not explained by negative cognitive errors in either gender.
      However, we found gender differences in how adversity and cognitive errors
      produced hyperactivity and internalizing problems. In particular, life adversity
      was not related, after adjustment for controls, to hyperactivity in girls and to
      peer problems and emotional symptoms in boys. Cognitive errors fully mediated the
      effect of life adversity on hyperactivity in boys and on peer and emotional
      problems in girls.

PMID- 21199499
TI  - Telling stories: gender differences in peers' emotion talk and communication
      style.
AB  - Eighty girls and 64 boys (M= 6 years; 8 months, SD= .65) narrated a wordless
      picture book in mixed- or same-gender dyads. In mixed-gender as well as same
      gender dyads, girls used more emotion explanations than did boys. Combined across
      dyad type, girls used more emotion labels than did boys. Girls used a higher
      proportion of collaborative speech acts than did boys in same-gender dyads, but
      girls and boys used the same amount in mixed-gender dyads. Whereas girls used a
      higher proportion of informing acts in mixed-gender dyads than did boys, boys
      used more than did girls in same-gender dyads. The findings support contextual
      models of gender and suggest that speaker as well as partner gender influence
      emotion expression and conversational style.

PMID- 21199500
TI  - Testing causal models of the relationship between childhood gender atypical
      behaviour and parent-child relationship.
AB  - An association between childhood gender atypical behaviour (GAB) and a negative
      parent-child relationship has been demonstrated in several studies, yet the
      causal relationship of this association is not fully understood. In the present
      study, different models of causation between childhood GAB and parent-child
      relationships were tested. Direction of causation modelling was applied to twin
      data from a population-based sample (n= 2,565) of Finnish 33- to 43-year-old
      twins. Participants completed retrospective self-report questionnaires. Five
      different models of causation were then fitted to the data: GAB -> parent-child
      relationship, parent-child relationship -> GAB, reciprocal causation, a bivariate
      genetic model, and a model assuming no correlation. It was found that a model in
      which GAB and quality of mother-child, and father-child relationship reciprocally
      affect each other best fitted the data. The findings are discussed in light of
      how we should understand, including causality, the association between GAB and
      parent-child relationship.

PMID- 21199501
TI  - Chilean children's essentialist reasoning about poverty.
AB  - Two studies are reported that examine the hypothesis that children construct
      representations of poverty based on a theory of causal essentialism. One hundred
      and twenty Chilean kindergartners, half from low socio-economic status (SES)
      schools and the other half from high-SES schools, participated in the study. The
      results showed children's tendency towards an essentialist reasoning about
      poverty. All children in the study privileged internal features over external
      ones when deciding who is poor, and also used wealth category as a preferred clue
      to make inferences about people's attributes. However, only high-SES children's
      answers were consistent with the belief that poverty is inherited and resistant
      to growth. Implications of these findings for theory and practice, as well as
      remaining questions, are addressed.

PMID- 21199502
TI  - The role of working memory in the development of emotion comprehension.
AB  - This study investigated the relationship between emotion comprehension, grammar
      comprehension, and working memory capacity in children between 5 and 11 years (n=
      130), testing the hypothesis that working memory has a role in the development of
      emotion comprehension. We replicated the correlation between emotion
      comprehension and grammar comprehension, and found that working memory capacity
      correlates with both of these variables (also with age statistically controlled).
      The significant effect of age on emotion comprehension was eliminated when
      working memory capacity was co-varied. In a regression analysis of emotion
      comprehension scores, when working memory capacity was entered as a predictor, no
      additional variance was significantly accounted for by grammar comprehension,
      gender, or age. A structural relations model, in which the paths from working
      memory capacity to emotion comprehension and from working memory capacity to
      grammar comprehension account fully for the correlation between grammar and
      emotion comprehension, fit the data well. However, working memory capacity was
      not equally related to all components of the Test of Emotion Comprehension (TEC)
      (Pons & Harris, 2000), the relationship being significant only for some of them.
      In particular, working memory capacity has a decisive role in the transition from
      understanding external to mental aspects of emotions. It is concluded that the
      development of working memory has a considerable impact on the development of
      emotion comprehension.

PMID- 21199503
TI  - The impact of novel labels on visual processing during infancy.
AB  - The impact of novel labels on visual processing was investigated across two
      experiments with infants aged between 9 and 21 months. Infants viewed pairs of
      images across a series of preferential looking trials. On each trial, one image
      was novel, and the other image had previously been viewed by the infant. Some
      infants viewed images in silence; other infants viewed images accompanied by
      novel labels. The pattern of fixations both across and within trials revealed
      that infants in the labelling condition took longer to develop a novelty
      preference than infants in the silent condition. Our findings contrast with prior
      research by Robinson and Sloutsky (e.g., Robinson & Sloutsky, 2007a; Sloutsky &
      Robinson, 2008) who found that novel labels did not disrupt visual processing for
      infants aged over a year. Provided that overall task demands are sufficiently
      high, it appears that labels can disrupt visual processing for infants during the
      developmental period of establishing a lexicon. The results suggest that when
      infants are processing labels and objects, attentional resources are shared
      across modalities.

PMID- 21199504
TI  - Situation-sensitive use of insincerity: pathways to communication in young
      children.
AB  - The present research focused on the development of children's ability to
      spontaneously suspend sincerity or tell a lie according to different
      communicative contexts. The issue of sincerity in communication is rather complex
      since in everyday interactions sincerity is expected, while there are specific
      communicative acts where sincerity is not prescribed or even banished. This study
      investigated how children (N= 80, ranging in age from 3 to 6.5 years) handled
      communications involving insincerity: fantasy stories, lies, and politeness
      situations. The results showed that the ability to deal with insincerity emerges
      gradually during the preschool years with an increasing trend of difficulty, from
      fantasy to politeness situations, and a notable amount of variability not equally
      distributed among the tasks.

PMID- 21199505
TI  - Preschoolers trust particular informants when learning new names and new
      morphological forms.
AB  - Across three studies, we investigated whether 4-year-olds would trust a
      previously reliable informant when learning novel morphological forms. In
      Experiment 1, children (N= 16) were presented with two informants: one who
      correctly named familiar objects and another who named them incorrectly. Children
      were invited to turn to these informants when learning novel labels and
      morphological forms. The majority of children chose the previously correct
      labeller when learning novel label and morphology. In Experiment 2, children (N=
      16) were presented with an informant who used familiar plurals correctly and one
      who used them incorrectly. Children chose the previously correct morphologist
      when learning novel labels and past tense forms. Thus, children track both
      semantic and morphological accuracy. In Experiment 3, some children (N= 16) were
      presented with two informants who differed in naming accuracy, whereas others (N=
      16) were presented with two informants who differed in morphological accuracy. To
      forestall any risk of experimenter cuing, one experimenter blind to the training
      children had received, tested children with novel labels and morphology. The
      results replicated those of Experiments 1 and 2. Implications for how children's
      trust in an informant might play a role in their acquisition of morphological
      forms are discussed.

PMID- 21199506
TI  - Anger response styles in Chinese and Dutch children: a socio-cultural perspective
      on anger regulation.
AB  - In this study, we evaluated hypotheses about cultural convergence and divergence
      in the nature and correlates of anger expressions. With a sample of 141 11-year
      olds from the Netherlands and Hong Kong, we first examined a broad range of
      strategies for responding to a provocateur, finding that both Chinese and Dutch
      children were more likely to use intrapersonal strategies (for coping internally
      with the angry feelings) than interpersonal responses (to communicate anger to
      the provocateur). No cultural divergence was shown in the overall extent to which
      anger would be verbally expressed, but differences became apparent when we asked
      children precisely what they would say to an aggressor in a hypothetical anger
      eliciting situation. As predicted, Chinese children were more likely to react
      tolerantly to the aggressor than their Dutch peers, whereas Dutch children
      indicated that they would verbally confront the aggressor more often, trying to
      reinstate their personal goals. In comparison with Dutch children, the Chinese
      sample viewed their chosen strategies as more likely to elicit positive reactions
      from the aggressor and to reduce anger. Directions for further research on the
      personal and socio-cultural functionality of anger response styles are discussed.

PMID- 21199507
TI  - Young children's racial awareness and affect and their perceptions about mothers'
      racial affect in a multiracial context.
AB  - There is a substantial literature documenting pre-schoolers' racial awareness and
      affect from multiracial societies in North America and a fast-growing body of
      work from societies that are or were once more racially homogeneous. However,
      studies in Britain, a racially diverse society, on this developmental period have
      been curiously rare. This study examined racial awareness and affect of 125
      White, Black, and Asian 3--to 5-year-olds in London. Children were tested on
      cognitive level, person description and classification, race labelling and
      matching, self-categorization and asked about their racial preference and
      rejection and inferences about their mothers' preference and rejection. Children
      were least likely to use race versus other categorical cues to spontaneously
      describe or classify others, even though the majority correctly sorted others by
      race labels, matched them to drawings, and categorized themselves by race. With
      age and increasing cognitive level, children described and categorized others by
      race more and improved in race matching. White children from age 4 preferred
      White peers and inferred that their mothers would prefer White children at age 5.
      Children's own preference and inference about mothers are related. Children did
      not show race-based rejection, but boys inferred that their mothers would prefer
      White children and reject Black children. The findings are discussed in relation
      to racial salience between contexts, previous research, and theories.

PMID- 21199508
TI  - The Silver Jubilee Supplement: Celebrating 25 years of JGH: A word from the
      Editor-in-Chief.

PMID- 21199509
TI  - Gastroesophageal reflux disease in Asia: A historical perspective and present
      challenges.
AB  - Gastroesophageal reflux disease (GERD), previously uncommon in Asia, has now
      become an important disease in the region. Although much variability exists
      between studies, most endoscopy-based studies show a prevalence of erosive
      esophagitis of more than 10%. Symptom-based studies also show a prevalence of 6
      10%. Two longitudinal follow-up studies on GERD symptoms have shown an increase
      with time, and several endoscopy-based time trend studies have also shown a
      significant increase in erosive reflux esophagitis. Studies on Barrett's
      esophagus have been confounded by the description of short (SSBE) and long
      segment (LSBE) Barrett's esophagus. Great variation in prevalence rates has been
      reported. SSBE vary from 0.1% to more than 20% while LSBE vary from 1-2%. Of the
      putative causative factors, obesity has been the most important. Many studies
      have linked GERD-esophagitis as well as occurrence of reflux symptoms with an
      increase in body mass index (BMI), obesity, especially visceral or central
      obesity, and metabolic syndrome. A decline in Helicobacter pylori infection with
      growing affluence in Asia has been broadly thought to result in healthier
      stomachs and a higher gastric acid output resulting in reflux disease. However,
      variable results have been obtained from association and H. pylori eradication
      studies.

PMID- 21199510
TI  - Barrett's esophagus: A historical perspective, an update on core practicalities
      and predictions on future evolutions of management.
AB  - Interpretation of exploding knowledge about Barrett's esophagus is impaired by
      use of several conflicting definitions. Because any histological type of
      esophageal columnar metaplasia carries risk for esophageal adenocarcinoma, the
      diagnosis of Barrett's esophagus should no longer require demonstration of
      intestinal-type metaplasia. Endoscopic recognition and grading of Barrett's
      esophagus remains a significant source of ambiguity. Reflux disease is a key
      factor for development of Barrett's esophagus, but other factors must underlie
      its development, since it occurs in only a minority of reflux disease patients.
      Neither antireflux surgery nor proton pump inhibitor (PPI) therapy has major
      impacts on cancer risk. Within a year, a major trial should indicate whether low
      dose aspirin usefully reduces cancer risk. The best referral centers have
      transformed the accuracy of screening and surveillance for early curable
      esophageal adenocarcinoma by use of enhanced and novel endoscopic imaging,
      visually-guided, rather than blind biopsies and by partnership with expert
      pathologists. General endoscopists now need to upgrade their skills and equipment
      so that they can rely mainly on visual targeting of biopsies on mucosal areas of
      concern in their surveillance practice. General pathologists need to greatly
      improve their interpretation of biopsies. Endoscopic therapy now achieves very
      high rates of cure of high-grade dysplasia and esophageal adenocarcinoma with
      minimal morbidity and risk. Such results will only be achieved by skilled
      interventional endoscopists. Esophagectomy should now be mainly restricted to
      patients whose cancer has extended into and beyond the submucosa. Weighing risks
      and benefits in the management of Barrett's esophagus is difficult, as is the
      process of adequately informing patients about their specific cancer risk.

PMID- 21199511
TI  - The Sydney System for classification of gastritis 20 years ago.
AB  - The roots of research into gastritis go back into the early decades of the 20th
      century. Modern aspects of its classification and knowledge of its biological
      course and consequences were relatively well known even at the time that
      Helicobcter pylori was discovered by Robin Warren and Barry Marshall in 1982.
      This discovery, however, significantly changed the field, establishing that the
      commonest form of gastritis is simply an infectious disease, a finding that
      raised enormous interest in the subject amongst gastroenterologists,
      microbiologists, pathologists and basic researchers. However, many of these "new"
      players in the field often had a limited knowledge of the morphological aspects
      of gastric inflammations and chronic gastritis. As a consequence in the late
      1980's a Working Party was set up to review the biology and natural course of
      chronic gastritis, to propose a new classification for gastritis, and to provide
      simple guidelines for reporting the pathology of gastritis in endoscopic biopsies
      in an attempt to bring uniformity to the subject and facilitate comparative
      studies in what was to be an era of high research activity. These guidelines, The
      Sydney System: A New Classification of Gastritis was presented to the World
      Congress of Gastroenterology in Sydney in 1990, and was later published as six
      papers in the Journal of Gastroenterology and Hepatology. Now, twenty years on,
      this review looks back on the birth of Sydney System and why it is still
      important and successful.

PMID- 21199512
TI  - The ulcer sleuths: The search for the cause of peptic ulcers.
AB  - The search for the cause or causes of peptic ulcers has been a long one. It was
      recognised as early as the 19th Century that damage to the stomach or duodenal
      bulb was likely to result if the resistance of their mucosae to luminal acid was
      for some reason impaired. An early theory suggested microscopic vascular
      occlusion leading to local infarction could be the initiating event but evidence
      was lacking. Excessive acid secretion is seen in some patients but not in many so
      is implausible as the main factor in most ulcers. Cigarette smoking is a risk
      factor and chronic life difficulties has been shown to sometimes play a part, but
      we would now think that they play only minor roles to possibly tip the balance
      when a major etiologic factor is already present. The overwhelming evidence now
      is that the major etiologic factors in chronic peptic ulcer are ingestion of
      nonsteroidal anti-inflammatory drugs (NSAIDs) and infection with Helicobacter
      pylori. Understanding the mechanism of the first, and the discovery and
      demonstration of Koch's postulates for the second, have been instrumental in the
      award of two Nobel prizes.

PMID- 21199513
TI  - Helicobacter pylori and gastritis: Untangling a complex relationship 27 years on.
AB  - Since its' introduction by Warren and Marshall 27 years ago, Helicobacter pylori
      (HP) has become the linchpin in our understanding of important gastric conditions
      including gastritis, intestinal metaplasia (IM), gastric/duodenal ulcers (GU/DU),
      Mucosal Associated Lymphoid Tumour (MALToma) and gastric cancer. Initially named
      Campylobacter pyloridis, it was re-named HP when biochemical and genetic
      characterization of the organism showed that it was not a member of the
      Campylobacter genus. The finding in 1983 was seminal. It is now recognized that
      HP is the most common chronic human bacterial infection and it is the most common
      cause of gastritis. It is strongly implicated in the development of peptic ulcer
      disease and gastric neoplasms. In the years since its' discovery, much headway
      has been made in the understanding of this ubiquitous organism that had remained
      elusive, with much work focused on eradication, in part driven by pharmaceutical
      research and development. Standard triple therapy emerged to eradicate HP.
      However, with the emergence of HP resistance, newer regimes have been put forth
      that include quadruple therapy, sequential therapy and a dizzying array of other
      combinations bent on eradicating HP. Much less is known about the natural history
      of HP, the different faces of HP internationally, HP eradication and its effect
      on gastritis, IM, GU/DU and gastric cancer. This review will address the changing
      face of HP in 2011.

PMID- 21199514
TI  - Diabetic gastroparesis-backwards and forwards.
AB  - Diabetic gastroparesis was once thought to be rare, associated with a poor
      prognosis, and to affect only patients with type 1 diabetes and irreversible
      autonomic neuropathy. A landmark study conducted by Horowitz et al. and published
      in JGH in 1986 paved the way for further studies to examine the pathophysiology,
      natural history and prognosis of diabetic gastroparesis, as well as its optimal
      management. This review summarizes the developments in knowledge gained over the
      last ~25 years that have led to understanding about normal and disordered gastric
      emptying in diabetes, with a particular emphasis on the inter-relationship
      between the rate of gastric emptying and the regulation of blood glucose.

PMID- 21199515
TI  - Clinicopathological staging of colorectal cancer: Evolution and consensus-an
      Australian perspective.
AB  - In 1991 this journal published the report of an international working party to
      the World Congress of Gastroenterology regarding the clinicopathological staging
      of colorectal cancer. Since that time staging has continued to evolve as further
      prognostic factors in colorectal cancer have been elucidated in studies of
      increasingly large databases in several countries. This review summarizes several
      of the key issues that have arisen during this evolutionary process and raises
      matters which still remain controversial in staging at the present time.

PMID- 21199516
TI  - Changing etiologies and outcomes of acute liver failure: A perspective from
      Japan.
AB  - Acute liver failure in Japan usually consists of fulminant hepatitis (FH) due to
      viral infection, autoimmune hepatitis and drug-allergy-induced liver injury. The
      annual incidence of FH was estimated at 429 cases in 2004. FH is classified into
      acute or subacute type, and the prognosis of the latter is poor. Hepatitis B
      virus (HBV) is the most frequently identifiable agent that causes FH in Japan.
      Transient HBV infection is more prevalent in the acute than subacute type,
      whereas the frequency of HBV carriers is greater in the subacute type. FH due to
      HBV reactivation from resolved hepatitis B has been increasingly observed in
      patients with malignant lymphoma treated with rituximab and corticosteroid
      combination therapy. The prognosis is poor in HBV carriers with acute
      exacerbation, especially in patients with HBV reactivation from resolved
      hepatitis B. Despite careful investigation, the etiology is still unknown in 16%
      and 39% of the acute and subacute type of FH, respectively. Autoimmune hepatitis
      and drug-allergy-induced liver injury are found in 7% and 10%, respectively, and
      are more frequently observed in the subacute type of FH. Living donor liver
      transplantation is now the standard care for individuals with poor prognosis.
      Artificial liver support with plasmapheresis and hemodiafiltration plays a
      central role while waiting for a donor liver or for the native liver to
      regenerate. Further research is necessary to identify the causes of unknown
      origin. In addition, to improve the prognosis of FH, it is necessary to establish
      treatment modalities that are effective for liver regeneration.

PMID- 21199517
TI  - Hepatitis E: Historical, contemporary and future perspectives.
AB  - Hepatitis E was suspected for the first time in 1980 during a waterborne epidemic
      of acute hepatitis in Kashmir, India. In the 30 years since then, a small virus
      with single-stranded RNA genome has been identified as the cause of this disease
      and named as hepatitis E virus (HEV). The virus has four genotypes; of these,
      genotypes 1 and 2 are known to infect only humans, whereas genotypes 3 and 4
      primarily infect other mammals, particularly pigs, but occasionally cause human
      disease. In highly-endemic areas, the disease occurs in epidemic and sporadic
      forms, caused mainly by infection with genotype 1 or 2 virus, acquired through
      the fecal-oral route, usually through contaminated water supplies. The disease is
      characterized by particularly severe course and high mortality among pregnant
      women. In persons with pre-existing chronic liver disease, HEV superinfection can
      present as acute-on-chronic liver disease. In low-endemic regions, sporadic cases
      of locally-acquired HEV infection are reported; these are caused mainly by
      genotype 3 or 4 HEV acquired possibly through zoonotic transmission from pigs,
      wild boars or deer. In these areas, chronic infection with genotype 3 HEV, which
      may progress to liver cirrhosis, has been reported among immunosuppressed
      persons. Two subunit vaccines containing recombinant truncated capsid proteins of
      HEV have been shown to be highly effective in preventing the disease; however,
      these are not yet commercially available. These vaccines should be of particular
      use in groups that are at high risk of HEV infection and/or of poor outcome.

PMID- 21199518
TI  - Hepatitis C virus: How genetic variability affects pathobiology of disease.
AB  - As an RNA virus, hepatitis C virus (HCV) shows a characteristically high level of
      nucleotide diversity. Accumulation of nucleotide substitutions in the virus has
      resulted in diversification into quasispecies, subtypes and distinct genotypes.
      Pathobiological studies linking nucleotide and amino acid sequences with clinical
      findings have identified relationships between certain genotypes and
      characteristic biological properties. Genotype 3 HCV infection was found to be
      associated with a high level of liver steatosis. Genotypes 1 and 4 were found to
      be more resistant to interferon (IFN) based therapies than genotypes 2 and 3.
      Studies of genotype 1 sequences obtained from patients treated with IFN have
      identified a relationship between favorable response to interferon therapy and
      amino acid substitutions in the NS5A region (interferon response determining
      region; ISDR). Further studies have identified a relationship between the effect
      of IFN therapy and other regions of the NS5A protein. More recently, a
      relationship has been found between poor response to peg-IFN plus ribavirin
      combination therapy and substitutions at amino acid 70 and 91 in the core
      protein. Furthermore, a correlation between human genetic variation in the IL28B
      (IFN-lamda 3) locus and core amino acid substitutions has been characterized. In
      this review we briefly summarize the discovery, classification and nomenclature
      of HCV genotypes and subtypes. We also discuss amino acid substitutions within
      specific regions that have been reported to be associated with outcome of IFN and
      peg-IFN plus ribavirin combination therapy.

PMID- 21199519
TI  - Hepatic steatosis and hepatitis C: Still unhappy bedfellows?
AB  - Hepatic steatosis is commonly seen in patients with chronic hepatitis C virus
      (HCV) infection, and the prevalence is much higher prevalence than in the general
      population or in patients with chronic hepatitis B. Hepatic steatosis in patients
      with chronic hepatitis C can be due to alcohol consumption and host metabolic
      factors such as high body mass index (BMI), obesity, hyperlipidemia, metabolic
      syndrome and diabetes mellitus in which insulin resistance plays an important
      role. However, in genotype 3 HCV infection, hepatic steatosis can result from
      direct viral cytopathic effect. Demographic and clinical characteristics
      associated with hepatic steatosis in patients with chronic hepatitis C including
      older age, higher BMI, more genotype 3 infection, and higher mean serum levels of
      triglyceride, alanine aminotransferase and gamma-glutamyl transpeptidase. The
      clinical relevance of hepatic steatosis in patients with chronic hepatitis C
      includes a close correlation with hepatic fibrosis, and a poor response to
      combination peginterferon and ribavirin treatment. In addition, hepatic steatosis
      has been reported to associate with increased frequency of hepatocellular
      carcinoma in patients with chronic HCV infection. Whether life style modification
      such as weight reduction or adding an insulin resistance reducing agent such as
      metformin or thiazolidinediones combined with current standard peginterferon plus
      ribavirin treatment will benefit to the chronic hepatitis C patients with hepatic
      steatosis deserves further evaluation.

PMID- 21199520
TI  - Management of gastric varices.
AB  - Although the incidence of bleeding from gastric varices is relatively low (10%
      36%), the bleeding is massive once it has occurred and it increases the patient's
      mortality. The management of esophageal variceal bleeding is highly
      differentiated with several effective treatments available. In contrast, bleeding
      from gastric varices continues to be a therapeutic challenge. In the last decade,
      there have been increasing reports regarding the management of gastric varices.
      In this article we review recent progress in the management of gastric varices
      and discuss further expected studies.

PMID- 21199521
TI  - Terlipressin in hepatorenal syndrome: Evidence for present indications.
AB  - Hepatorenal syndrome (HRS) is the most frequent life threatening complication of
      advanced liver failure and cirrhosis. HRS results from a functional renal
      dysfunction due to circulatory disturbances in patients with advanced liver
      disease and portal hypertension. Reduction in the effective circulating blood
      volume and hence hypoperfusion of the kidney is the basic underlying common
      pathogenetic mechanism for the development of hepatorenal syndrome. The prognosis
      for HRS remains very poor with types 1 and 2-both having an expected survival
      time of 2 weeks and 6 months, respectively. Although the available data are
      derived from studies including a limited number of patients mainly affected by
      type 1 HRS, vasoconstrictor drugs, in particular the vasopressin analog
      Terlipressin, seem to be the most effective approach for the management of HRS.
      Associated with albumin infusion, these drugs have been shown to lead to reduced
      mortality and improved renal function in HRS. Terlipressin administration
      significantly increases mean arterial pressure and systemic vascular resistance;
      while the heart rate, cardiac output, HVPG and portal venous blood flow decrease
      significantly. This decrease correlates well with the decrease in plasma renin
      activity. Thus the vasoconstrictor effect of Terlipressin reverses the basic
      pathology of HRS by reducing the plasma renin activity. The improvement in
      hemodynamics with Terlipressin is associated with an increase in glomerular
      filtration rate and deactivation of the vasoconstrictor and sodium-conserving
      hormones with reduced activity of the RAAS resulting in increased natriuresis.
      Terlipressin thus reverses HRS and is useful in bridging the patient to liver
      transplantation and may hence indirectly improve survival. Patients with HRS who
      show an improvement in renal function with Terlipressin and albumin seem to have
      an excellent post-transplantation outcome similar to that of patients without
      HRS. Thus, the use of Terlipressin has been shown to be safe, with minimal side
      effects that usually disappear after dose reduction, and results in an improved
      outcome in patients with HRS.

PMID- 21199522
TI  - Recent advances of radiofrequency ablation for early hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the third leading cause of death in the
      malignant neoplastic diseases in the world. Surgical operation is sometimes not
      indicated because of complicated liver cirrhosis and extrahepatic disorders.
      Radiofrequency ablation has been developed as a less invasive treatment for HCC
      since 1999, and long-term outcome has been shown. There are several complications
      which should be paid attention, and to improve the prognosis, combination
      treatment with transarterial chemoembolization should be discussed. Overall
      survival after between RFA and surgical resection should be compared
      prospectively. Establishment of staging system for treatment allocation of HCC
      and prevention of HCC recurrence is important issue to be examined.

PMID- 21199523
TI  - The clinical implications of hepatitis B virus genotype: Recent advances.
AB  - Outcomes of chronic hepatitis B virus (HBV) infection are heterogeneous.
      Estimates of annual incidence of cirrhosis and hepatocellular carcinoma (HCC) are
      2-10% and 1-3%, respectively. Several viral factors, including HBV genotype,
      viral load and specific viral mutations, have been associated with disease
      progression. Among these, HBV genotype is not only predictive of clinical
      outcomes but has also been associated with response to interferon treatment.
      Currently, at least 10 HBV genotypes and several subtypes have been identified;
      they have distinct geographic distribution. Acute infection with genotypes A and
      D results in higher rates of chronicity than genotypes B and C. Compared to
      genotype A and B cases, patients with genotypes C and D have lower rates of
      spontaneous hepatitis B e antigen (HBeAg) seroconversion; when this occurs, it
      tends to be delayed. HBV genotype C has a higher frequency of basal core promoter
      (BCP) A1762T/G1764A mutation, pre-S deletion and is associated with higher viral
      load than genotype B. Similarly, genotype D has a higher prevalence of BCP
      A1762T/G1764A mutation than genotype A. These observations suggest important
      pathogenic differences between HBV genotypes. These may contribute to more severe
      liver disease, including cirrhosis and HCC with genotypes C and D HBV infection.
      In addition, genotype A and B patients have better responses to interferon-based
      therapy than genotypes C and D, but there are few consistent differences for
      direct HBV antivirals. In conclusion, genotyping of chronic HBV infections can
      help practicing physicians identify those at risk of disease progression and
      determine optimal anti-viral therapy.

PMID- 21199524
TI  - Chronic hepatitis B in Asia-new insights from the past decade.
AB  - Chronic hepatitis B virus (HBV) infection is a major health problem in the Asia
      Pacific region. In the past decade, much progress has been made in the
      understanding and management of this disease. The introduction of universal
      vaccination has significantly reduced the incidence of perinatal infection in
      most Asia-Pacific countries. As the majority of the adult population have not
      been immunized at birth, we are still facing a large population of young HBV
      infected patients in the coming two decades. The study of long-term longitudinal
      databases has provided deeper insight into the clinical significance of HBV DNA
      suppression, hepatitis B e antigen (HBeAg) seroconversion and hepatitis B surface
      antigen (HBsAg) seroclearance in chronic hepatitis B. With a better understanding
      on the natural history of HBV infection, one can now stratify the risk of chronic
      hepatitis B patients for adverse clinical outcomes and use this to individualize
      management. The introduction of non-invasive assessment of liver fibrosis can
      potentially reduce the necessity of liver biopsy. There have also been great
      advances in the development of antiviral therapy in the past decade. However, the
      high cost of HBV antiviral drugs poses major challenges to health authorities in
      many Asia-Pacific countries. Properly performed cost-effective analysis and
      understanding on the best timing of stopping antiviral drugs will be important to
      facilitate the most appropriate allocation of resources.

PMID- 21199525
TI  - Treatment of chronic hepatitis B: Evolution over two decades.
AB  - There has been a recent paradigm shift in the indications and endpoints of
      treatment for chronic hepatitis B (CHB). Hepatitis B e antigen (HBeAg)-negative
      disease is being increasingly recognized. Antiviral treatment for both HBeAg
      positive and HBeAg-negative patients should aim at long-term suppression of HBV
      DNA, with the ultimate ideal endpoint of hepatitis B surface antigen (HBsAg)
      seroconversion. Conventional interferon alpha (IFN-alpha), the only agent
      licensed in 1991, has been superseded by pegylated IFN-alpha. HBeAg
      seroconversion using pegylated IFN-alpha is 33%, with only 25% of HBeAg-positive
      patients achieving undetectable HBV DNA by polymerase chain reaction (PCR) assay.
      Five nucleoside/nucleotide analogues have been licensed since 1998. Lamivudine,
      an L-nucleoside, is limited by the development of resistance in 76% of patients
      after 5 years of therapy. Telbivudine, another L-nucleoside, is more potent than
      lamivudine but resistance still develops in 25% of HBeAg-positive and 11% HBeAg
      negative patients after 2 years. Adefovir, an acyclic phosphonate, is relatively
      weak, but is effective against lamivudine- and telbivudine- resistant mutations,
      for which it should be used in combination (add-on therapy) rather than
      substituted. Resistance to adefovir develops slowly, rising to 29% for HBeAg
      negative patients by year 5, but more rapidly when used alone for lamivudine
      resistant HBV. Currently the two first line nucleoside/nucleotides are entecavir
      and tenofovir. Entecavir, a cyclopentane (D-nucleoside), is very potent, with 94%
      of patients having undetectable HBV DNA after 5 years. Resistance develops in
      only 1.2% of treatment-naive patients. Tenofovir, another acyclic nucleotide, is
      more potent with less renal toxicity compared to adefovir. It is effective
      against lamivudine-resistant mutations when used alone. No resistance to
      tenofovir has been described after its use for 3 years or longer, often for
      patients with human immunodeficiency virus/HBV co-infection. With these current,
      potent antiviral agents associated with very low rates of resistance, long-term
      HBV DNA suppression and possibly even reversal of cirrhosis can now be achieved
      in a proportion of patients. In addition, long-term treatment with these
      antiviral agents is associated with a reduced risk of development of
      hepatocellular carcinoma.

PMID- 21199526
TI  - Hepatitis B virus x protein in the pathogenesis of hepatitis B virus-induced
      hepatocellular carcinoma.
AB  - Currently available evidence supports a role for the hepatitis B virus (HBV) x
      gene and protein in the pathogenesis of HBV-induced hepatocellular carcinoma
      (HCC). HBx gene is often included, and remains functionally active, in the HBV
      DNA that is frequently integrated into cellular DNA during hepatocellular
      carcinogenesis. HBx protein promotes cell cycle progression, inactivates negative
      growth regulators, and binds to and inhibits the expression of p53 tumour
      suppressor gene and other tumour suppressor genes and senescence-related factors.
      However, the molecular mechanisms responsible for HBx protein-induced HCC remain
      uncertain. Only some of the more fully documented or more recently recognised
      mechanisms are reviewed. During recent years evidence has accumulated that HBx
      protein modulates transcription of methyl transferases, causing regional
      hypermethylation of DNA that results in silencing of tumour suppressor genes, or
      global hypomethylation that results in chromosomal instability, thereby playing a
      role in hepatocarcinogenesis. HBx protein has both anti-apoptotic and pro
      apoptotic actions, apparently contradictory effects that have yet to be
      explained. Particularly important among the anti-apoptotic properties is
      inhibition of p53. Recent experimental observations suggest that HBx protein may
      increase the expression of TERT and telomerase activity, prolonging the life-span
      of hepatocytes and contributing to malignant transformation. The protein also
      interferes with nucleotide excision repair through both p53-dependent and p53-
      independent mechanisms. Carboxy-terminal truncated HBx protein loses its
      inhibitory effects on cell proliferation and pro-apoptotic properties, and it may
      enhance the protein's ability to transform oncogenes. Dysregulation of IGF-II
      enhances proliferation and anti-apoptotic effects of oncogenes, resulting in
      uncontrolled cell growth.

PMID- 21199527
TI  - Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in Japan.
AB  - During the past 20 to 30 years, the frequency of patients presenting with
      nonalcoholic fatty liver diseases (NAFLD) has increased gradually in Japan in
      proportion to the increase in the population with life-style related diseases. We
      describe here the current status of the clinical and basic aspects of research
      into NAFLD in Japan. The increase in the incidence of life-style-related diseases
      has resulted in an increase in NAFLD throughout the past 20 to 30 years. The rate
      of obesity in the population is not high compared to western countries but the
      incidence of NAFLD is similar to those countries. In 2008 we started a nationwide
      study of NAFLD which has been supported by the Ministry of Labor and Welfare
      Japan. In this project, we planned to investigate the epidemiology, genetic
      backgrounds and biochemical markers, and liver injury in patients with diabetes
      mellitus (DM) and hepatocellular carcinoma in NASH, and treatment of NASH.
      Approximately 20 to 25% of DM patients showed NAFLD in which the prevalence of
      NASH might be more than 30 to 40%. Fortunately, we have been able to obtain very
      interesting results from our group studies, including single necleotide
      polymorphisms (SNPs) which will be published in the near future.

PMID- 21199528
TI  - Nonalcoholic fatty liver in Asia: Firmly entrenched and rapidly gaining ground.
AB  - Nonalcoholic fatty liver disease (NAFLD) is becoming an important chronic liver
      disorder in Asia. Prevalence figures show regional variations but at least 10% of
      the general population in Asia have fatty liver. Fatty liver can develop with
      relatively small changes in weight (2-3 kg), often with increasing central
      adiposity. The metabolic syndrome may precede or follow NAFLD. Overt diabetes is
      present in one-third of cases but when oral glucose tolerance tests are
      performed, a further third of individuals have impaired glucose tolerance or
      diabetes. Natural history data are still scarce but cases of advanced hepatic
      fibrosis and hepatocellular carcinoma are now regularly reported. Many cases of
      cryptogenic cirrhosis are also attributable to NAFLD. Histological progression
      has been demonstrated for patients with NASH as well as for those with hepatic
      steatosis alone. Genetic factors may in part contribute to the rise in NAFLD.
      Polymorphisms within apolipoprotein C3 (APOC3) gene have been linked to NAFLD in
      lean Indian men. Although a number of other polymorphisms involving genes
      controlling adipose distribution, insulin signalling, adipokine responses and
      hepatic fibrosis have been reported, these studies have been underpowered.
      Transient elastography could help in detecting and monitoring hepatic fibrosis
      but further refinements in technique are necessary for obese individuals. Of the
      biomarkers, hyaluronic acid and cytokeratin-18 fragment testing show promise as
      markers of hepatic fibrosis and NASH, respectively. Lifestyle alterations
      including dietary changes and increased physical activity remain the cornerstone
      of management. Attention should be paid to prevention through public education of
      campaigns addressing the increase in both adult and childhood obesity.

PMID- 21199529
TI  - Reactive oxygen and mechanisms of inflammatory liver injury: Present concepts.
AB  - Liver cell death induced by stresses such as ischemia-reperfusion, cholestasis
      and drug toxicity can trigger a sterile inflammatory response with activation of
      innate immune cells through release of damage-associated molecular patterns
      (DAMPs). A similar inflammatory response can be induced by pathogen-associated
      molecular patterns (PAMPs) such as endotoxin. Both DAMPs and PAMPs activate
      through toll-like receptors the resident macrophages (Kupffer cells) and recruit
      activated neutrophils and monocytes into the liver. Central to this inflammatory
      response is promotion of reactive oxygen species (ROS) formation by these
      phagocytes. ROS are the principal toxic mediators by which inflammatory cells
      kill their targets, e.g. bacteria during host defense but also hepatocytes and
      other liver cells. The mechanism of ROS-induced cell killing during inflammation
      involves the promotion of mitochondrial dysfunction through an intracellular
      oxidant stress in hepatocytes leading mainly to oncotic necrosis and less
      apoptosis. The additional release of cell contents amplifies the inflammatory
      injury. However, an inflammatory oxidant stress insufficient to directly cause
      cell damage can induce transcription of stress defence genes including
      antioxidant genes. This preconditioning effect of ROS enhances the resistance
      against future inflammatory oxidant stress and promotes the initiation of tissue
      repair processes. Despite the substantial progress in our understanding of
      mechanisms of inflammatory liver injury during the last decade, more research is
      necessary to better understand the role of ROS in acute liver inflammation and to
      develop clinically applicable therapeutic strategies that selectively target the
      detrimental effects of oxidant stress without compromising the vital function of
      ROS in host defense.

PMID- 21199530
TI  - Hepatic ischemia reperfusion injury: Contemporary perspectives on pathogenic
      mechanisms and basis for hepatoprotection-the good, bad and deadly.
AB  - Hepatic ischemia reperfusion (IR) injury is an important clinical problem
      complicating liver surgery and transplantation. The pathogenesis underlying
      reperfusion injury after warm ischemia is complex, encompassing a multitude of
      different cell types and signalling mechanisms innate and/or mobilized to the
      liver. Since the author's 2003 review in the Journal, considerable progress has
      been achieved in enhancing our understanding of some of the pathogenic pathways
      and crucial mediators of hepatic inflammation such as the heme oxygenase system,
      CXC chemokines, Toll-like receptors as well as the mode of parenchymal cell death
      in IR injury. A better appreciation of these mechanisms will accelerate efforts
      in designing optimal interventions to prevent hepatic IR injury and improve
      outcomes after liver transplantation.

PMID- 21199531
TI  - Hepatocyte growth factor twenty years on: Much more than a growth factor.
AB  - Liver regeneration depends on the proliferation of mature hepatocytes. In the
      1980s, the method for the cultivation of mature hepatocytes provided an
      opportunity for the discovery of hepatocyte growth factor (HGF) as a protein that
      is structurally and functionally different from other growth factors. In 1991,
      the scatter factor, tumor cytotoxic factor, and 3-D epithelial morphogen were
      identified as HGF, and Met tyrosine kinase was identified as the receptor for
      HGF. Thus, the connection of apparently unrelated research projects rapidly
      enriched the research on HGF in different fields. The HGF-Met pathway plays
      important roles in the embryonic development of the liver and the placenta, in
      the migration of myogenic precursor cells, and in epithelial morphogenesis. The
      use of tissue-specific knockout mice demonstrated that in mature tissues the HGF
      Met pathway plays a critical role in tissue protection and regeneration, and in
      providing less susceptibility to chronic inflammation and fibrosis. In various
      injury and disease models, HGF promotes cell survival, regeneration of tissues,
      and suppresses and improves chronic inflammation and fibrosis. Drug development
      using HGF has been challenging, but extensive preclinical studies to address its
      therapeutic effects have provided significant results sufficient for the
      development of HGF as a biological drug in the regeneration-based therapy of
      diseases. Clinical trials using recombinant human HGF protein, or HGF genes, are
      in progress for the treatment of diseases.

PMID- 21199533
TI  - Cell death and hepatocarcinogenesis: Dysregulation of apoptosis signaling
      pathways.
AB  - Hepatocellular carcinoma (HCC) remains a disease with a poor prognosis despite
      recent advances in the pathophysiology and treatment. Although the disease is
      biologically heterogeneous, dysregulation of cellular proliferation and apoptosis
      both occur frequently and contribute to the malignant phenotype. Chronic liver
      disease is associated with intrahepatic inflammation which promotes dysregulation
      of cellular signaling pathways; this triggers proliferation and thus lays the
      ground for expansion of premalignant cells. Cancer emerges when immunological
      control fails and transformed cells develop resistance against cell death
      signaling pathways. The same mechanisms underlie the poor responsiveness of HCC
      towards chemotherapy. Only recently advances in understanding the signaling
      pathways involved has led to the development of an effective pharmacological
      therapy for advanced disease. The current review will discuss apoptosis signaling
      pathways and focus on apoptosis resistance of HCC involving derangements in cell
      death receptors (e.g. tumor necrosis factor-alpha [TNF], CD95/Apo-1, TNF-related
      apoptosis-inducing ligand [TRAIL]) and associated adapter molecules (e.g. FADD
      and FLIP) of apoptotic signaling pathways. In addition, the role of the
      transcription factor nuclear factor-kappaB (NFkappaB) and members of the B cell
      leukemia-2 (Bcl-2) family that contribute to the regulation of apoptosis in
      hepatocytes are discussed. Eventually, the delineation of cell death signaling
      pathways could contribute to the implementation of new therapeutic strategies to
      treat HCC.

PMID- 21199532
TI  - New concepts in liver regeneration.
AB  - The unique ability of the liver to regenerate itself has fascinated biologists
      for years and has made it the prototype for mammalian organ regeneration.
      Harnessing this process has great potential benefit in the treatment of liver
      failure and has been the focus of intense research over the past 50 years. Not
      only will detailed understanding of cell proliferation in response to injury be
      applicable to other dysfunction of organs, it may also shed light on how cancer
      develops in a cirrhotic liver, in which there is intense pressure on cells to
      regenerate. Advances in molecular techniques over the past few decades have led
      to the identification of many regulatory intermediates, and pushed us onto the
      verge of an explosive era in regenerative medicine. To date, more than 10
      clinical trials have been reported in which augmented regeneration using
      progenitor cell therapy has been attempted in human patients. This review traces
      the path that has been taken over the last few decades in the study of liver
      regeneration, highlights new concepts in the field, and discusses the challenges
      that still stand between us and clinical therapy.

PMID- 21199534
TI  - Reply to: Prevalence of immediate vasovagal reaction in blood donors visiting two
      blood banks of Karachi.

PMID- 21199535
TI  - The analgesic effects of the GABAB receptor agonist, baclofen, in a rodent model
      of functional dyspepsia.
AB  - BACKGROUND: The amino acid gamma-aminobutyric acid (GABA) is an important
      modulator of pain but its role in visceral pain syndromes is just beginning to be
      studied. Our aims were to investigate the effect and mechanism of action of the
      GABA(B) receptor agonist, baclofen, on gastric hypersensitivity in a validated
      rat model of functional dyspepsia (FD). METHODS: 10-day-old male rats received
      0.2 mL of 0.1% iodoacetamide in 2% sucrose daily by oral gavages for 6 days.
      Control group received 2% sucrose. At 8-10 weeks rats treated with baclofen (0.3,
      1, and 3 mg kg(-1) bw) or saline were tested for behavioral and electromyographic
      (EMG) visceromotor responses; gastric spinal afferent nerve activity to graded
      gastric distention and Fos protein expression in dorsal horn of spinal cord
      segments T8-T10 to noxious gastric distention. KEY RESULTS: Baclofen
      administration was associated with a significant attenuation of the behavioral
      and EMG responses (at 1 and 3 mg kg(-1)) and expression of Fos in T8 and T9
      segments in neonatal iodoacetamide sensitized rats. However, baclofen
      administration did not significantly affect splanchnic nerve activity to gastric
      distention. Baclofen (3 mg kg(-1)) also significantly reduced the expression of
      spinal Fos in response to gastric distention in control rats to a lesser extent
      than sensitized rats. CONCLUSIONS & INFERENCES: Baclofen is effective in
      attenuating pain associated responses in an experimental model of FD and appears
      to act by central mechanisms. These results provide a basis for clinical trials
      of this drug in FD patients.

PMID- 21199537
TI  - Adherence to medication in stroke survivors: a qualitative comparison of low and
      high adherers.
AB  - OBJECTIVES: The aim of this study was to investigate factors that may explain
      variance in adherence to medication in stroke patients. Design. A qualitative
      comparison of high and low adherers to medication. METHODS: Thirteen
      participants, selected from a sample of 180 stroke survivors because they self
      reported the lowest adherence to medication regimes, were matched with 13
      reporting maximal adherence. All took part in semi-structured qualitative
      interviews. RESULTS: Thematic analysis revealed that those with poor adherence to
      medication reported both intentional and non-intentional non-adherence. Two main
      themes emerged: the importance of stability of a medication routine and beliefs
      about medication and treatment. High adherers reported remembering to take their
      medication and seeking support from both family and health professionals. They
      also had a realistic understanding of the consequences of non-adherence, and
      believed their medicine did them more good than harm. Low adherers reported
      forgetting their medication, sometimes intentionally not taking their medication
      and receiving poor support from medical staff. They disliked taking their
      medication, had limited knowledge about the medication rationale or intentions,
      and often disputed its benefits. CONCLUSIONS: Our findings suggest that
      appropriate medication and illness beliefs coupled with a stable medication
      routine are helpful in achieving optimal medication adherence in stroke patients.
      Interventions designed to target both intentional and non-intentional adherence
      may help maximize medication adherence in stroke patients.

PMID- 21199536
TI  - Anatomical registration and three-dimensional visualization of low and high
      resolution pan-colonic manometry recordings.
AB  - BACKGROUND: Colonic propagating sequences (PS) are important for the movement of
      colonic content and defecation, and aberrant PS patterning has been associated
      with slow transit constipation. However, because these motor patterns are
      typically recorded over long periods (24 h +), the visualization of PS
      spatiotemporal patterning is difficult. Here, we develop a novel method for
      displaying pan-colonic motility patterns. METHODS: A 3D mesh representing the
      geometry of the human colon was created as follows: (i) Human colon images from
      the Visible Human Dataset were digitized to create a 3D data cloud, and (ii) A
      surface mesh was fitted to the cloud using a least-squares minimization
      technique. Colonic manometry catheters were placed in the ascending colon of
      healthy controls and patients with slow transit constipation (STC), with the aid
      of a colonoscope. The colonic manometry data were interpolated and mapped to the
      model according to the following anatomical landmarks: cecum, hepatic flexure,
      splenic flexure, sigmoid-descending junction, and anus. KEY RESULTS: These 3D
      images clearly and intuitively communicate characteristics of normal and abnormal
      colonic motility. Specifically we have shown the reduced amplitude of the
      antegrade propagating pressure waves (PPW) throughout the colon and reduced
      frequency of PPWs at the mid-colon in patients with STC. CONCLUSIONS AND
      INFERENCES: A novel method for the 3D visualization of PS is presented, providing
      an intuitive method for representing a large volume of physiological data. These
      techniques can be used to display frequency, amplitude or velocity data, and will
      help to convey regions of abnormally in patient populations.

PMID- 21199538
TI  - Smoking-specific compensatory health beliefs and the readiness to stop smoking in
      adolescents.
AB  - OBJECTIVE: Compensatory health beliefs (CHBs) are defined as beliefs that
      negative consequences of unhealthy behaviours can be compensated for by engaging
      in other health behaviours. CHBs have not yet been investigated in detail
      regarding smoking. Smoking might cause cognitive dissonance in smokers, if they
      are aware that smoking is unhealthy and simultaneously hold the general goal of
      staying healthy. Hence, CHBs are proposed as one strategy for smokers to resolve
      such cognitive dissonance. The aim of the present study was to develop a scale to
      measure smoking-specific CHBs among adolescents and to test whether CHBs are
      related to a lower readiness to stop smoking. DESIGN: For the main analyses,
      cross-sectional data were used. In order to investigate the retest-reliability
      follow-up data, 4 months later were included in the analysis. METHOD: A newly
      developed scale for smoking-specific CHBs in adolescents was tested for its
      validity and reliability as well as its predictive value for the readiness to
      stop smoking in a sample of 244 smokers (15-21 years) drawn from different
      schools. Multilevel modelling was applied. RESULTS: Evidence was found for the
      reliability and validity of the smoking-specific CHB scale. Smoking-specific CHBs
      were significantly negatively related to an individual's readiness to stop
      smoking, even after controlling for other predictors such as self-efficacy or
      conscientiousness. CONCLUSIONS: CHBs may provide one possible explanation for why
      adolescents fail to stop smoking.

PMID- 21199539
TI  - Maternal perceptions of overweight and obesity in children: a grounded theory
      study.
AB  - OBJECTIVES: To develop a theoretical framework for understanding maternal
      perceptions of overweight and obesity in children. METHOD: Semi-structured
      interviews with 12 mothers of overweight or obese children recruited via the
      paediatrician or local weight management group. Interviews were transcribed and
      analysed using Grounded Theory methodology. RESULTS: Using Grounded Theory, a
      theoretical understanding of maternal perceptions of overweight and obesity in
      children was developed using the two over-arching core categories of 'Good
      mum/bad mum' and 'Resilience'. CONCLUSION: Results supported findings uncovered
      in previous research and also expand on these findings by offering explanations
      about the psychological mechanisms that may mediate maternal misperceptions of
      overweight.

PMID- 21199540
TI  - Family caregivers' attributions about care-recipient behaviour: does caregiver
      relationship satisfaction mediate the attribution-distress relationship?
AB  - OBJECTIVES: The relations of caregiver attributions about care-recipient's
      problem behaviour to caregiving relationship satisfaction and caregiver distress
      were examined. DESIGN: This is a cross sectional study. Seventy-five family
      caregivers of individuals diagnosed with various disabling health conditions were
      recruited and interviewed. Caregiver attributions (internality, intentionality,
      responsibility, and controllability), caregiving relationship satisfaction, and
      caregiver distress variables were measured. RESULTS: Structural equation
      techniques tested an a priori model of the latent constructs of caregiver
      attributions and caregiver relationship satisfaction to caregiver distress.
      Maladaptive caregiver attributions (i.e., more trait, higher intentionality,
      higher responsibility, and higher controllability) about care-recipients' problem
      behaviours predicted lower caregiving relationship satisfaction, which in turn
      was predictive of higher caregiver distress. Unexpectedly, caregiver attributions
      were not directly related to caregiver distress. However, attributions had an
      indirect effect on distress through relationship satisfaction. Younger caregivers
      experienced higher caregiver distress. CONCLUSIONS: Caregivers' explanations
      about care-recipient's problem behaviour are indicative of their satisfaction in
      the relationship with the care recipient, and poor caregiving relationship
      satisfaction is predictive of caregiver distress. Caregiver attributions and
      relationship quality may be considered in interventions with family caregivers.

PMID- 21199541
TI  - Survivor identity and post-traumatic growth after participating in challenge
      based peer-support programmes.
AB  - OBJECTIVES: The social construction of breast cancer (BC) survivor identity has
      produced a powerful image of woman as survivor. Group membership through peer
      support programmes can provide positive role models, shape survivor identity and
      promote post-traumatic growth (PTG). The main objective of this study was to
      conduct a qualitative investigation based on a phenomenological framework in
      order to understand the lived experience of BC survivors participating in a peer
      support programme based on a challenge event. DESIGN: This is a qualitative semi
      structured and written narrative study. Interviews were subjected to
      interpretative phenomenological analysis and the written narratives via thematic
      analysis. METHOD: Interviews were conducted with 27 participants who were new to
      the peer-support event for women diagnosed with BC, and 10 participants who had
      taken part in multiple events provided written narratives of their experience.
      Interviews and surveys were completed pre- and post-event. RESULTS: Important
      elements of the peer-support environment included a safe network of other
      survivors, which provided understanding and acceptance. Overcoming challenges
      during the event and the opportunity to bond with positive role models affirmed a
      strong survivor identity and promoted PTG. For some participants, a shift in
      identity was evident with a newfound positive identification with the term BC
      survivor. CONCLUSIONS: Peer-support programmes based on challenge events have the
      potential to extend the type of supportive care that is available for women
      diagnosed with BC by providing an alternative to the traditional support group
      format.

PMID- 21199542
TI  - Paving the path for habit change: cognitive shielding of intentions against habit
      intrusion.
AB  - OBJECTIVE: The objective of the current study was to examine the cognitive
      processes that make it possible to use intentions to change one's habitual health
      related behaviour. DESIGN: The study used an idiosyncratic approach to
      investigate personal existing habits and non-habitual behaviours in a within
      participants experiment. METHOD: Participants first generated habitual and non
      habitual behaviours for various daily-life goals (e.g., having lunch, playing
      sports). Next, they formed intentions to perform non-habitual behaviours in order
      to attain these goals. Finally, we measured the cognitive accessibility of
      participants' habitual and non-habitual behaviours with a behaviour recognition
      task. RESULTS: The findings showed that habitual behaviours were more accessible
      than the non-habitual behaviours when no intentions were formed (control goals),
      showing that habits are more readily accessed in mind. However, when participants
      had formed intentions to use non-habitual behaviours, habitual behaviours for the
      same goals were inhibited in mind. This could be the cognitive mechanism that
      shields intentions from habit intrusion and thus enables the pursuit of non
      habitual behaviours. CONCLUSION: The current study demonstrates the role of
      inhibitory processes in shielding non-habitual intentions in memory. These
      findings are discussed in the context of success and failure in changing health
      related habits.

PMID- 21199543
TI  - Women smokers' experiences of an age-appearance anti-smoking intervention: a
      qualitative study.
AB  - OBJECTIVES: This study was designed to investigate women's experiences of
      engaging in an age-appearance anti-smoking intervention. METHODS: Ten 18- to 34
      year-old women gave accounts of their experiences after engaging in an age
      appearance facial morphing anti-smoking intervention in interviews (n= 7) and a
      focus group (n= 3), and 37 women gave their accounts while they were engaged in
      the intervention. Transcripts were analysed using a thematic analysis broadly
      informed by the procedures of Grounded Theory. RESULTS: Women were very concerned
      about the impact of ageing on their faces in general, and in particular the
      additional impact of smoking on their skin. Women were concerned about other
      people's reactions to them as older smokers with wrinkled skin, and many
      experienced a physical shock reaction (including reports of nausea) to seeing how
      they would age if they continued to smoke. They reported that seeing their own
      face aged on the computer screen increased their perceived risk of skin
      wrinkling. Women reported being highly motivated to quit smoking as a result of
      the intervention, and many reported that they would take active steps to quit
      having seen how they would look if they continued to smoke. This was linked with
      increased perceived personal responsibility for quitting. CONCLUSIONS: Results
      are discussed in relation to suggestions for anti-smoking interventions aimed at
      women in the 18- to 34-year-old age group. It is concluded that interventions
      incorporating age-appearance morphing techniques are likely to be effective in
      helping women to take active steps to quit smoking.

PMID- 21199544
TI  - Getting healthcare staff more active: the mediating role of self-efficacy.
AB  - OBJECTIVES: Physical activity has been associated with positive health outcomes.
      The objective of the study was to investigate the relationship between knowledge
      of physical activity, social support, self-efficacy, perceived barriers to
      physical activity, and level of physical activity among healthcare employees and
      students in a National Health Service (NHS) Trust. DESIGN: This study was
      secondary analysis of questionnaire data on the health and well-being of staff
      and students within the NHS. METHOD: A total of 325 student nurses and 1,452 NHS
      employees completed the questionnaire. The data were analysed using descriptive
      statistics, zero-order correlations, and structural equation modelling. results:
      Self-efficacy fully mediated the relationship between social support, perceived
      barriers, and level of physical activity in the student sample and partially
      mediated the relationship between social support, perceived barriers, and level
      of physical activity in the healthcare staff sample. Knowledge of physical
      activity had no significant effect on physical activity. CONCLUSION: Findings
      suggest that instead of instilling knowledge, interventions to promote physical
      activity among healthcare staff and students should enhance social support and
      self-efficacy and also to remove perceived barriers to physical activity.

PMID- 21199546
TI  - The development of a scale measuring integrated regulation in exercise.
AB  - OBJECTIVES: This research aimed to develop and validate a measure of integrated
      regulation based on self-determination theory (SDT) in an exercise context.
      DESIGN: Cross-sectional and prospective surveys were employed. METHODS: The
      measure was developed from first principles from an initial item pool and items
      were selected using expert evaluators. The validity of the final item pool was
      tested across a high-active sample and a lower active sample (N= 488) using
      single- and multi-sample confirmatory factor analyses (CFAs). RESULTS: Analyses
      supported the factorial, nomological, discriminant, and predictive validity of
      the scale. CONCLUSIONS: The validity of the integrated regulation measure was
      supported. Present analyses provide evidence that the scale is a valid and
      reliable tool that may be used to evaluate the effectiveness of autonomy
      supportive interventions in health-related behavioural contexts.

PMID- 21199548
TI  - The role of non-blaming culture in learning from errors.

PMID- 21199549
TI  - Interprofessional collaboration in the ICU: how to define?
AB  - The intensive care unit (ICU) is a dynamic, complex and, at times, highly
      stressful work environment that involves ongoing exposure to the complexities of
      interprofessional team functioning. Failures of communication, considered
      examples of poor collaboration among health care professionals, are the leading
      cause of inadvertent harm across all health care settings. Evidence suggests
      effective interprofessional collaboration results in improved outcomes for
      critically ill patients. One recent study demonstrated a link between low
      standardized mortality ratios and self-identified levels of collaboration. The
      aim of this paper is to discuss determinants and complexities of
      interprofessional collaboration, the evidence supporting its impact on outcomes
      in the ICU, and interventions designed to foster better interprofessional team
      functioning. Elements of effective interprofessional collaboration include shared
      goals and partnerships including explicit, complementary and interdependent
      roles; mutual respect; and power sharing. In the ICU setting, teams continually
      alter due to large staff numbers, shift work and staff rotations through the
      institution. Therefore, the ideal 'unified' team working together to provide
      better care and improve patient outcomes may be difficult to sustain. Power
      sharing is one of the most complex aspects of interprofessional collaboration.
      Ownership of specialized knowledge, technical skills, clinical territory, or even
      the patient, may produce interprofessional conflict when ownership is not
      acknowledged. Collaboration by definition implies interdependency as opposed to
      autonomy. Yet, much nursing literature focuses on achievement of autonomy in
      clinical decision-making, cited to improve job satisfaction, retention and
      patient outcomes. Autonomy of health care professionals may be an inappropriate
      goal when striving to foster interprofessional collaboration. Tools such as
      checklists, guidelines and protocols are advocated, by some, as ways for nurses
      to gain influence and autonomy in clinical decision-making. Protocols to guide
      ICU practices such as sedation and weaning reduce the duration of mechanical
      ventilation in some studies, while others have failed to demonstrate this
      advantage. Existing organizational strategies that facilitate effective
      collaboration between health care professionals may contribute to this lack of
      effect.

PMID- 21199550
TI  - Family members' satisfaction with critical care: a pilot study.
AB  - AIM: the aim of this pilot study was to describe family members' satisfaction
      with the care provided in a Swedish intensive care unit (ICU) based on the
      following needs: assurance, information, proximity, support, and comfort, which
      are all included in the Critical Care Family Satisfaction Survey (CCFSS).
      BACKGROUND: knowledge concerning satisfaction with care among family members with
      a critically ill relative in an ICU is important if the family is to be met
      professionally. DESIGN: the study design was descriptive and retrospective, with
      a consecutive selection of family members of critically ill people cared for in
      an ICU. In total 35 family members participated. METHOD: quantitative analyses
      based on 20 questions, and a qualitative analysis, based on two open questions
      was used. The median, average value and percent were computed for every question.
      The open questions were analyzed using qualitative content analysis. RESULTS: the
      family members had a high level of satisfaction regarding all groups of needs.
      They were especially satisfied with flexible visiting hours and the high quality
      of treatment that the ill person received. The shortcomings that emerged were
      that family members wanted the physician to be more available for regular talks,
      the room for relatives was felt to be uncomfortable; and it was felt there were
      deficiencies in the preparations before the patient's transferral to a ward.
      RELEVANCE TO CLINICAL PRACTICE: the results highlight the family members' need
      for regular information and the need to improve the environment in the waiting
      rooms for family members. The ICU staff's competence and their way of
      encountering the ill person and their family seem to be important for family
      members' satisfaction with the care.

PMID- 21199551
TI  - Using the prone position for ventilated patients with respiratory failure: a
      review.
AB  - AIMS: this review explored the evidence relating to prone positioning in
      ventilated patients diagnosed with respiratory failure, including acute lung
      injury (ALI) or adult respiratory distress syndrome (ARDS). BACKGROUND: mortality
      rates for ventilated patients with ALI or ARDS are high, and there is a growing
      body of evidence suggesting that the position these patients are nursed in may
      influence clinical outcomes. However, there are no guidelines to inform nursing
      practice in positioning these patients. METHOD: Medline, Scopus, Cinahl and the
      Cochrane Library databases were searched for original research reports or
      systematic reviews of evidence between 2000 and 2009. Reference lists of
      retrieved papers were hand searched and included studies were analysed using the
      Critical Appraisal and Skills Programme framework. A narrative data synthesis
      considered the strengths and limitations of studies, and findings were collated
      and interpreted. RESULTS: Application of the search strategy identified a
      systematic review, currently underway, which has not yet reported and 14 relevant
      studies eligible for inclusion in this review. Analysis showed considerable
      variation in study design, but suggests that PaO(2) /FiO(2) ratio, incidence of
      VAP and mortality may be positively affected by prone positioning. CONCLUSIONS:
      evidence of the clinical benefits associated with prone positioning is
      inconclusive and provides little guidance for nursing practice. There is a need
      for further research into the clinical outcomes of prone positioning, and greater
      understanding of the practicalities of prone positioning critically ill patients
      is required. RELEVANCE TO CLINICAL PRACTICE: nurses have a central role to play
      in the continual assessment and management of this patient group, including the
      position they are nursed in, not only to ensure the best clinical outcomes but
      also to provide care and comfort to the patient and their family. It is therefore
      important that their nursing practice and interventions are informed by the best
      available evidence.

PMID- 21199552
TI  - Understanding the effects of oxygen administration in haemorrhagic shock.
AB  - AIMS AND OBJECTIVES: the aim of this article is to provide a review of the
      literature regarding oxygen administration and the use of oxygen in patients
      experiencing haemorrhagic shock (HS). RESULTS: oxygen is administered to patients
      to assist them in maintaining oxygenation. The administration of oxygen is
      complex and varies significantly among patients. In order to optimize patient
      care, clinicians need to be aware of the potential effects, both beneficial and
      harmful, that oxygen can have on the body. INCLUSION AND EXCLUSION CRITERIA:
      literature inclusion criteria for this article was any article (1995 to present)
      pertaining to oxygen administration and HS. Also included were articles related
      to tissue injury caused by an overabundance of free radicals with the
      administration of oxygen. Articles related to oxygen and wound healing,
      pollution, aerospace, food and industrial uses were excluded. CONCLUSIONS: this
      review of the literature provides an overview of the use of oxygen in clinical
      practice and HS. The harmful effects of oxygen are highlighted to alert the
      clinician to this potential when there is an overabundance of oxygen. RELEVANCE
      TO CLINICAL PRACTICE: oxygen is one of the most common drugs used in the medical
      community; however, the effects of oxygen on the body are not well understood.
      The use of oxygen if not prescribed correctly can cause cellular damage and
      death. Clinicians need to be more aware of the effects of oxygen and the damage
      it may cause if not administered properly.

PMID- 21199553
TI  - Nursing leadership at the crossroads: evidence-based practice 'Matching Michigan
      minimizing catheter related blood stream infections'(*).
AB  - AIMS AND OBJECTIVES: a highly successful intervention to reduce infections in
      intensive care units (ICUs) is now being widely replicated and involved
      significant nursing leadership. The objective of this manuscript is to describe
      briefly the intervention, and more explicitly the implications for nursing
      leadership as quality improvement and patient safety become global healthcare
      priorities. DESIGN: collaborative cohort study in over 100 ICUs in the United
      States to implement and evaluate interventions to improve patients' safety.
      METHODS: conceptual model aimed at improving clinicians' use of five evidence
      based recommendations to reduce rates of catheter-related bloodstream infections
      rates, with measurement and feedback of infection rates. RESULTS: one hundred and
      three ICUs contributed 1981 ICU-months of data representing 375,757 catheter
      days. The median rate of catheter-related bloodstream infection per 1000 catheter
      days decreased from 2.7 infections at baseline to 0 at 3 months after
      implementation of the study intervention (P <= 0.002), and the mean rate per 1000
      catheter-days decreased from 7.7 at baseline to 1.4 at 16-18 months of follow-up
      (P < 0.002). During the sustainability period, the mean bloodstream infection
      rate did not significantly change from the initial 18 month postimplementation
      period (-1%, 95% confidence interval -9% to 7%). Eighty seven percent of the
      original study participants had data available for the sustainability study.
      CONCLUSIONS: broad use of this intervention with achievement of similar results
      could substantially reduce the morbidity and costs associated with catheter
      related bloodstream infections. RELEVANCE TO CLINICAL PRACTICE: the initial
      Michigan study and the follow-up analysis, that demonstrated sustained
      improvements, are leading to similar projects in other countries, include the
      Matching Michigan project in England. Discussing not only the technical
      components of the program, but also the nursing leadership aspects may assist
      nurses just embarking on this work.

PMID- 21199556
TI  - NICE Clinical Guideline on organ donation.

PMID- 21199562
TI  - Venturia inaequalis: the causal agent of apple scab.
AB  - The fungus Venturia inaequalis infects members of the Maloideae, and causes the
      disease apple scab, the most important disease of apple worldwide. The early
      elucidation of the gene-for-gene relationship between V. inaequalis and its host
      Malus has intrigued plant pathologists ever since, with the identification of 17
      resistance (R)-avirulence (Avr) gene pairings. The Avr gene products are
      presumably a subset of the total effector arsenal of V. inaequalis (predominantly
      proteins secreted in planta assumed to facilitate infection). The supposition
      that effectors from V. inaequalis act as suppressors of plant defence is
      supported by the ability of the pathogen to penetrate the cuticle and
      differentiate into large pseudoparenchymatous structures, termed stromata, in the
      subcuticular space, without the initiation of an effective plant defence
      response. If effectors can be identified that are essential for pathogenicity,
      the corresponding R genes will be durable and would add significant value to
      breeding programmes. An R gene cluster in Malus has been cloned, but no V.
      inaequalis effectors have been characterized at the molecular level. However, the
      identification of effectors is likely to be facilitated by the resolution of the
      whole genome sequence of V. inaequalis. TAXONOMY: Teleomorph: Venturia inaequalis
      Cooke (Wint.); Kingdom Fungi; Phylum Ascomycota; Subphylum Euascomycota; Class
      Dothideomycetes; Family Venturiaceae; genus Venturia; species inaequalis.
      Anamorph: Fusicladium pomi (Fr.) Lind or Spilocaea pomi (Fr.). LIFE CYCLE: V.
      inaequalis is a hemibiotroph and overwinters as pseudothecia (sexual fruiting
      bodies) following a phase of saprobic growth in fallen leaf tissues. The primary
      inoculum consists of ascospores, which germinate and penetrate the cuticle.
      Stromata are formed above the epidermal cells but do not penetrate them. Cell
      wall-degrading enzymes are only produced late in the infection cycle, raising the
      as yet unanswered question as to how V. inaequalis gains nutrients from the host.
      Conidia (secondary inoculum) arise from the upper surface of the stromata, and
      are produced throughout the growing season, initiating multiple rounds of
      infection. VENTURIA INAEQUALIS AS A MODEL PATHOGEN OF A WOODY HOST: V. inaequalis
      can be cultured and is amenable to crossing in vitro, enabling map-based cloning
      strategies. It can be transformed readily, and functional analyses can be
      conducted by gene silencing. Expressed sequence tag collections are available to
      aid in gene identification. These will be complemented by the whole genome
      sequence, which, in turn, will contribute to the comparative analysis of
      different races of V. inaequalis and plant pathogens within the Dothideomycetes.

PMID- 21199563
TI  - Elsinoe fawcettii and Elsinoe australis: the fungal pathogens causing citrus
      scab.
AB  - Elsinoe fawcettii and E. australis are important pathogens of citrus. Both
      species are known to produce red or orange pigments, called elsinochrome.
      Elsinochrome is a nonhost-selective phytotoxin and is required for full fungal
      virulence and lesion formation. This article discusses the taxonomy,
      epidemiology, genetics and pathology of the pathogens. It also provides a
      perspective on the cellular toxicity, biosynthetic regulation and pathological
      role of elsinochrome phytotoxin. TAXONOMY: Elsinoe fawcettii (anamorph:
      Sphaceloma fawcettii) and E. australis (anamorph: S. australis) are classified in
      the Phylum Ascomycota, Class Dothideomycetes, Order Myriangiales and Family
      Elsinoaceae. HOST RANGE: Elsinoe fawcettii causes citrus scab (formerly sour
      orange scab and common scab) on various species and hybrids in the Rutaceae
      family worldwide, whereas E. australis causes sweet orange scab, primarily on
      sweet orange and some mandarins, and has a limited geographical distribution.
      DISEASE SYMPTOMS: Citrus tissues infested with Elsinoe often display erumpent
      scab pustules with a warty appearance. TOXIN PRODUCTION: Elsinochrome and many
      perylenequinone-containing phytotoxins of fungal origin are grouped as
      photosensitizing compounds that are able to absorb light energy, react with
      oxygen molecules and produce reactive oxygen species, such as superoxide and
      singlet oxygen. Elsinochrome has been documented to cause peroxidation of cell
      membranes and to induce rapid electrolyte leakage from citrus tissues.
      Elsinochrome biosynthesis and conidiation are coordinately regulated in E.
      fawcettii, and the environmental and physiological inducers commonly involved in
      both processes have begun to be elucidated.

PMID- 21199564
TI  - The 20S proteasome alpha5 subunit of Arabidopsis thaliana carries an RNase
      activity and interacts in planta with the lettuce mosaic potyvirus HcPro protein.
AB  - In plants, the ubiquitin/26S proteasome system (UPS) plays a central role in
      protein degradation and is involved in many steps of defence mechanisms,
      regardless of the types of pathogen targeted. In addition to its proteolytic
      activities, the UPS ribonuclease (RNase) activity, previously detected in 20S
      proteasome preparations from cauliflower and sunflower (Helianthus annuus), has
      been shown to specifically target plant viral RNAs in vitro. In this study, we
      show that recombinant Arabidopsis thaliana proteasomal alpha(5) subunit expressed
      in Escherichia coli harbours an RNase activity that degrades Tobacco mosaic virus
      (TMV, Tobamovirus)- and Lettuce mosaic virus (LMV, Potyvirus)-derived RNAs in
      vitro. The analysis of mutated forms of the alpha(5) subunit demonstrated that
      mutation of a glutamic acid at position 110 affects RNase activity. Furthermore,
      it was demonstrated, using a bimolecular fluorescence complement assay, that the
      multifunctional helper component proteinase (HcPro) of LMV, already known to
      interfere with the 20S proteasome RNase activity in vitro, can interact in vivo
      with the recombinant alpha(5) subunit. Further experiments demonstrated that, in
      LMV-infected lettuce cells, alpha(5) is partially relocalized to HcPro-containing
      infection-specific inclusions. Susceptibility analyses of Arabidopsis mutants,
      knocked out for each At-PAE gene encoding alpha(5) , showed that one (KO-pae1) of
      the two mutants exhibited a significantly increased susceptibility to LMV
      infection. Taken together, these results extend to A. thaliana alpha(5) the range
      of HcPro-interacting proteasomal subunits, and suggest that HcPro may modulate
      its associated RNase activity which may contribute to an antiviral response.

PMID- 21199565
TI  - Functional mapping of harpin HrpZ of Pseudomonas syringae reveals the sites
      responsible for protein oligomerization, lipid interactions and plant defence
      induction.
AB  - Harpin HrpZ is one of the most abundant proteins secreted through the
      pathogenesis-associated type III secretion system of the plant pathogen
      Pseudomonas syringae. HrpZ shows membrane-binding and pore-forming activities in
      vitro, suggesting that it could be targeted to the host cell plasma membrane. We
      studied the native molecular forms of HrpZ and found that it forms dimers and
      higher order oligomers. Lipid binding by HrpZ was tested with 15 different
      membrane lipids, with HrpZ interacting only with phosphatidic acid. Pore
      formation by HrpZ in artificial lipid vesicles was found to be dependent on the
      presence of phosphatidic acid. In addition, HrpZ was able to form pores in
      vesicles prepared from Arabidopsis thaliana plasma membrane, providing evidence
      for the suggested target of HrpZ in the host. To map the functions associated
      with HrpZ, we constructed a comprehensive series of deletions in the hrpZ gene
      derived from P. syringae pv. phaseolicola, and studied the mutant proteins. We
      found that oligomerization is mainly mediated by a region near the C-terminus of
      the protein, and that the same region is also essential for membrane pore
      formation. Phosphatidic acid binding seems to be mediated by two regions separate
      in the primary structure. Tobacco, a nonhost plant, recognizes, as a defence
      elicitor, a 24-amino-acid HrpZ fragment which resides in the region indispensable
      for the oligomerization and pore formation functions of HrpZ.

PMID- 21199566
TI  - In planta conditions induce genomic changes in Pseudomonas syringae pv.
      phaseolicola.
AB  - The co-evolution of bacterial plant pathogens and their hosts is a complex and
      dynamic process. Plant resistance can impose stress on invading pathogens that
      can lead to, and select for, beneficial changes in the bacterial genome. The
      Pseudomonas syringae pv. phaseolicola (Pph) genomic island PPHGI-1 carries an
      effector gene, avrPphB (hopAR1), which triggers the hypersensitive reaction in
      bean plants carrying the R3 resistance gene. Interaction between avrPphB and R3
      generates an antimicrobial environment within the plant, resulting in the
      excision of PPHGI-1 and its loss from the genome. The loss of PPHGI-1 leads to
      the generation of a Pph strain able to cause disease in the plant. In this study,
      we observed that lower bacterial densities inoculated into resistant bean
      (Phaseolus vulgaris) plants resulted in quicker PPHGI-1 loss from the population,
      and that loss of the island was strongly influenced by the type of plant
      resistance encountered by the bacteria. In addition, we found that a number of
      changes occurred in the bacterial genome during growth in the plant, whether or
      not PPHGI-1 was lost. We also present evidence that the circular PPHGI-1 episome
      is able to replicate autonomously when excised from the genome. These results
      shed more light onto the plasticity of the bacterial genome as it is influenced
      by in planta conditions.

PMID- 21199567
TI  - Identification of potential host plant mimics of CLAVATA3/ESR (CLE)-like peptides
      from the plant-parasitic nematode Heterodera schachtii.
AB  - In this article, we present the cloning of two CLAVATA3/ESR (CLE)-like genes,
      HsCLE1 and HsCLE2, from the beet cyst nematode Heterodera schachtii, a plant
      parasitic cyst nematode with a relatively broad host range that includes the
      model plant Arabidopsis. CLEs are small secreted peptide ligands that play
      important roles in plant growth and development. By secreting peptide mimics of
      plant CLEs, the nematode can developmentally reprogramme root cells for the
      formation of unique feeding sites within host roots for its own benefit. Both
      HsCLE1 and HsCLE2 encode small secreted polypeptides with a conserved C-terminal
      CLE domain sharing highest similarity to Arabidopsis CLEs 1-7. Moreover, HsCLE2
      contains a 12-amino-acid CLE motif that is identical to AtCLE5 and AtCLE6. Like
      all other plant and nematode CLEs identified to date, HsCLEs caused wuschel-like
      phenotypes when overexpressed in Arabidopsis, and this activity was abolished
      when the proteins were expressed without the CLE motif. HsCLEs could also
      function in planta without a signal peptide, highlighting the unique, yet
      conserved function of nematode CLE variable domains in trafficking CLE peptides
      for secretion. In a direct comparison of HsCLE2 overexpression phenotypes with
      those of AtCLE5 and AtCLE6, similar shoot and root phenotypes were observed.
      Exogenous application of 12-amino-acid synthetic peptides corresponding to the
      CLE motifs of HsCLEs and AtCLE5/6 suggests that the function of this class of
      CLEs may be subject to complex endogenous regulation. When seedlings were grown
      on high concentrations of peptide (10 um), root growth was suppressed; however,
      when seedlings were grown on low concentrations of peptide (0.1 um), root growth
      was stimulated. Together, these findings indicate that AtCLEs1-7 may be the
      target peptides mimicked by HsCLEs to promote parasitism.

PMID- 21199568
TI  - Infection of Arabidopsis thaliana by Phytophthora parasitica and identification
      of variation in host specificity.
AB  - Oomycete pathogens cause severe damage to a wide range of agriculturally
      important crops and natural ecosystems. They represent a unique group of plant
      pathogens that are evolutionarily distant from true fungi. In this study, we
      established a new plant-oomycete pathosystem in which the broad host range
      pathogen Phytophthora parasitica was demonstrated to be capable of interacting
      compatibly with the model plant Arabidopsis thaliana. Water-soaked lesions
      developed on leaves within 3 days and numerous sporangia formed within 5 days
      post-inoculation of P. parasitica zoospores. Cytological characterization showed
      that P. parasitica developed appressoria-like swellings and penetrated epidermal
      cells directly and preferably at the junction between anticlinal host cell walls.
      Multiple haustoria-like structures formed in both epidermal cells and mesophyll
      cells 1 day post-inoculation of zoospores. Pathogenicity assays of 25 A. thaliana
      ecotypes with six P. parasitica strains indicated the presence of a natural
      variation in host specificity between A. thaliana and P. parasitica. Most
      ecotypes were highly susceptible to P. parasitica strains Pp014, Pp016 and Pp025,
      but resistant to strains Pp008 and Pp009, with the frequent appearance of cell
      wall deposition and active defence response-based cell necrosis. Gene expression
      and comparative transcriptomic analysis further confirmed the compatible
      interaction by the identification of up-regulated genes in A. thaliana which were
      characteristic of biotic stress. The established A. thaliana-P. parasitica
      pathosystem expands the model systems investigating oomycete-plant interactions,
      and will facilitate a full understanding of Phytophthora biology and pathology.

PMID- 21199569
TI  - Two nucleotide positions in the Citrus exocortis viroid RNA associated with
      symptom expression in Etrog citron but not in experimental herbaceous hosts.
AB  - Citrus exocortis viroid (CEVd) is the causal agent of exocortis disease of
      citrus. CEVd has a wide host range that includes woody and herbaceous species. A
      new CEVd strain (CEVd(COL)), phylogenetically clustering with CEVd variants of
      Class A inducing severe symptoms in tomato, was identified in Colombia and shown
      to induce only extremely mild symptoms in Etrog citron indicator plants. Using
      site-directed mutagenesis, two nucleotide substitutions (314A -> G and 315U -> A)
      in the lower strand of the P domain of the predicted CEVd(COL) secondary
      structure resulted in a severe artificial CEVd(MCOL) variant. Conversely, two
      nucleotide exchanges (314G -> A and 315A -> U) in the same region of the severe
      variant CEVd(E-117) resulted in a symptomless artificial CEVd(ME-117) variant.
      Infectivity assays conducted with the natural and mutated variants showed that
      all induced severe symptoms in Gynura aurantiaca, tomato and chrysanthemum. This
      is the first report of the identification of pathogenic determinants of CEVd in
      citrus, and shows that these pathogenicity determinants are host dependent.

PMID- 21199570
TI  - The development of instruments to measure the work disability assessment
      behaviour of insurance physicians.
AB  - BACKGROUND: Variation in assessments is a universal given, and work disability
      assessments by insurance physicians are no exception. Little is known about the
      considerations and views of insurance physicians that may partly explain such
      variation. On the basis of the Attitude--Social norm--self Efficacy (ASE) model,
      we have developed measurement instruments for assessment behaviour and its
      determinants. METHODS: Based on theory and interviews with insurance physicians
      the questionnaire included blocks of items concerning background variables,
      intentions, attitudes, social norms, self-efficacy, knowledge, barriers and
      behaviour of the insurance physicians in relation to work disability assessment
      issues. The responses of 231 insurance physicians were suitable for further
      analysis. Factor analysis and reliability analysis were used to form scale
      variables and homogeneity analysis was used to form dimension variables. Thus, we
      included 169 of the 177 original items. RESULTS: Factor analysis and reliability
      analysis yielded 29 scales with sufficient reliability. Homogeneity analysis
      yielded 19 dimensions. Scales and dimensions fitted with the concepts of the ASE
      model. We slightly modified the ASE model by dividing behaviour into two blocks:
      behaviour that reflects the assessment process and behaviour that reflects
      assessment behaviour.The picture that emerged from the descriptive results was of
      a group of physicians who were motivated in their job and positive about the
      Dutch social security system in general. However, only half of them had a
      positive opinion about the Dutch Work and Income (Capacity for Work) Act (WIA).
      They also reported serious barriers, the most common of which was work pressure.
      Finally, 73% of the insurance physicians described the majority of their cases as
      'difficult'. CONCLUSIONS: The scales and dimensions developed appear to be valid
      and offer a promising basis for future research. The results suggest that the
      underlying ASE model, in modified form, is suitable for describing the assessment
      behaviour of insurance physicians and the determinants of this behaviour. The
      next step in this line of research should be to validate the model using
      structural equation modelling. Finally, the predictive value should be tested in
      relation to outcome measurements of work disability assessments.

PMID- 21199571
TI  - Perceived risk, anxiety, and behavioural responses of the general public during
      the early phase of the Influenza A (H1N1) pandemic in the Netherlands: results of
      three consecutive online surveys.
AB  - BACKGROUND: Research into risk perception and behavioural responses in case of
      emerging infectious diseases is still relatively new. The aim of this study was
      to examine perceptions and behaviours of the general public during the early
      phase of the Influenza A (H1N1) pandemic in the Netherlands. METHODS: Two cross
      sectional and one follow-up online survey (survey 1, 30 April-4 May; survey 2, 15
      19 June; survey 3, 11-20 August 2009). Adults aged 18 years and above
      participating in a representative Internet panel were invited (survey 1, n = 456;
      survey 2, n = 478; follow-up survey 3, n = 934). Main outcome measures were 1)
      time trends in risk perception, feelings of anxiety, and behavioural responses
      (survey 1-3) and 2) factors associated with taking preventive measures and strong
      intention to comply with government-advised preventive measures in the future
      (survey 3). RESULTS: Between May and August 2009, the level of knowledge
      regarding Influenza A (H1N1) increased, while perceived severity of the new flu,
      perceived self-efficacy, and intention to comply with preventive measures
      decreased. The perceived reliability of information from the government decreased
      from May to August (62% versus 45%). Feelings of anxiety decreased from May to
      June, and remained stable afterwards. From June to August 2009, perceived
      vulnerability increased and more respondents took preventive measures (14% versus
      38%). Taking preventive measures was associated with no children in the
      household, high anxiety, high self-efficacy, more agreement with statements on
      avoidance, and paying much attention to media information regarding Influenza A
      (H1N1). Having a strong intention to comply with government-advised preventive
      measures in the future was associated with higher age, high perceived severity,
      high anxiety, high perceived efficacy of measures, high self-efficacy, and
      finding governmental information to be reliable. CONCLUSIONS: Decreasing trends
      over time in perceived severity and anxiety are consistent with the reality: the
      clinical picture of influenza turned out to be mild in course of time. Although
      (inter)national health authorities initially overestimated the case fatality
      rate, the public stayed calm and remained to have a relatively high intention to
      comply with preventive measures.

PMID- 21199572
TI  - Markers of thrombogenesis are activated in unmedicated patients with acute
      psychosis: a matched case control study.
AB  - BACKGROUND: Antipsychotic treatment has been repeatedly found to be associated
      with an increased risk for venous thromboembolism in schizophrenia. The extent to
      which the propensity for venous thromboembolism is linked to antipsychotic
      medication alone or psychosis itself is unclear. The objective of this study was
      to determine whether markers of thrombogenesis are increased in psychotic
      patients who have not yet been treated with antipsychotic medication. METHODS: We
      investigated the plasma levels of markers indicating activation of coagulation (D
      dimers and Factor VIII) and platelets (soluble P-selectin, sP-selectin) in an
      antipsychotic-naive group of fourteen men and eleven women with acute psychosis
      (age 29.1 +/- 8.3 years, body mass index 23.6 +/- 4.7), and twenty-five healthy
      volunteers were matched for age, gender and body mass index. RESULTS: D-dimers
      (median 0.38 versus 0.19 mg/l, mean 1.12 +/- 2.38 versus 0.28 +/- 0.3 mg/l; P =
      0.003) and sP-selectin (median 204.1 versus 112.4 ng/ml, mean 209.9 +/- 124
      versus 124.1 +/- 32; P = 0.0005) plasma levels were significantly increased in
      the group of patients with acute psychosis as compared with healthy volunteers.
      We found a trend (median 148% versus 110%, mean 160 +/- 72.5 versus 123 +/- 62.5;
      P = 0.062) of increased plasma levels of factor VIII in psychotic patients as
      compared with healthy volunteers. CONCLUSIONS: The results suggest that at least
      a part of venous thromboembolic events in patients with acute psychosis may be
      induced by pathogenic mechanisms related to psychosis rather than by
      antipsychotic treatment. Finding an exact cause for venous thromboembolism in
      psychotic patients is necessary for its effective treatment and prevention.

PMID- 21199573
TI  - Ascorbic acid partly antagonizes resveratrol mediated heme oxygenase-1 but not
      paraoxonase-1 induction in cultured hepatocytes - role of the redox-regulated
      transcription factor Nrf2.
AB  - BACKGROUND: Both resveratrol and vitamin C (ascorbic acid) are frequently used in
      complementary and alternative medicine. However, little is known about the
      underlying mechanisms for potential health benefits of resveratrol and its
      interactions with ascorbic acid. METHODS: The antioxidant enzymes heme oxygenase
      1 and paraoxonase-1 were analysed for their mRNA and protein levels in HUH7 liver
      cells treated with 10 and 25 MUmol/l resveratrol in the absence and presence of
      100 and 1000 MUmol/l ascorbic acid. Additionally the transactivation of the
      transcription factor Nrf2 and paraoxonase-1 were determined by reporter gene
      assays. RESULTS: Here, we demonstrate that resveratrol induces the antioxidant
      enzymes heme oxygenase-1 and paraoxonase-1 in cultured hepatocytes. Heme
      oxygenase-1 induction by resveratrol was accompanied by an increase in Nrf2
      transactivation. Resveratrol mediated Nrf2 transactivation as well as heme
      oxygenase-1 induction were partly antagonized by 1000 MUmol/l ascorbic acid.
      CONCLUSIONS: Unlike heme oxygenase-1 (which is highly regulated by Nrf2)
      paraoxonase-1 (which exhibits fewer ARE/Nrf2 binding sites in its promoter)
      induction by resveratrol was not counteracted by ascorbic acid. Addition of
      resveratrol to the cell culture medium produced relatively low levels of hydrogen
      peroxide which may be a positive hormetic redox-signal for Nrf2 dependent gene
      expression thereby driving heme oxygenase-1 induction. However, high
      concentrations of ascorbic acid manifold increased hydrogen peroxide production
      in the cell culture medium which may be a stress signal thereby disrupting the
      Nrf2 signalling pathway.

PMID- 21199575
TI  - The quality of care for adults with epilepsy: an initial glimpse using the QUIET
      measure.
AB  - BACKGROUND: We examined the quality of adult epilepsy care using the Quality
      Indicators in Epilepsy Treatment (QUIET) measure, and variations in quality based
      on the source of epilepsy care. METHODS: We identified 311 individuals with
      epilepsy diagnosis between 2004 and 2007 in a tertiary medical center in New
      England. We abstracted medical charts to identify the extent to which
      participants received quality indicator (QI) concordant care for individual QI's
      and the proportion of recommended care processes completed for different aspects
      of epilepsy care over a two year period. Finally, we compared the proportion of
      recommended care processes completed for those receiving care only in primary
      care, neurology clinics, or care shared between primary care and neurology
      providers. RESULTS: The mean proportion of concordant care by indicator was 55.6
      (standard deviation = 31.5). Of the 1985 possible care processes, 877 (44.2%)
      were performed; care specific to women had the lowest concordance (37% vs. 42%
      [first seizure evaluation], 44% [initial epilepsy treatment], 45% [chronic
      care]). Individuals receiving shared care had more aspects of QI concordant care
      performed than did those receiving neurology care for initial treatment (53% vs.
      43%; X(2) = 9.0; p = 0.01) and chronic epilepsy care (55% vs. 42%; X(2) = 30.2; p
      < 0.001). CONCLUSIONS: Similar to most other chronic diseases, less than half of
      recommended care processes were performed. Further investigation is needed to
      understand whether a shared-care model enhances quality of care, and if so, how
      it leads to improvements in quality.

PMID- 21199574
TI  - (R)-[11C]verapamil PET studies to assess changes in P-glycoprotein expression and
      functionality in rat blood-brain barrier after exposure to kainate-induced status
      epilepticus.
AB  - BACKGROUND: Increased functionality of efflux transporters at the blood-brain
      barrier may contribute to decreased drug concentrations at the target site in CNS
      diseases like epilepsy. In the rat, pharmacoresistant epilepsy can be mimicked by
      inducing status epilepticus by intraperitoneal injection of kainate, which leads
      to development of spontaneous seizures after 3 weeks to 3 months. The aim of this
      study was to investigate potential changes in P-glycoprotein (P-gp) expression
      and functionality at an early stage after induction of status epilepticus by
      kainate. METHODS: (R)-[11C]verapamil, which is currently the most frequently used
      positron emission tomography (PET) ligand for determining P-gp functionality at
      the blood-brain barrier, was used in kainate and saline (control) treated rats,
      at 7 days after treatment. To investigate the effect of P-gp on (R)
      [11C]verapamil brain distribution, both groups were studied without or with co
      administration of the P-gp inhibitor tariquidar. P-gp expression was determined
      using immunohistochemistry in post mortem brains. (R)-[11C]verapamil kinetics
      were analyzed with approaches common in PET research (Logan analysis, and
      compartmental modelling of individual profiles) as well as by population mixed
      effects modelling (NONMEM). RESULTS: All data analysis approaches indicated only
      modest differences in brain distribution of (R)-[11C]verapamil between saline and
      kainate treated rats, while tariquidar treatment in both groups resulted in a
      more than 10-fold increase. NONMEM provided most precise parameter estimates. P
      gp expression was found to be similar for kainate and saline treated rats.
      CONCLUSIONS: P-gp expression and functionality does not seem to change at early
      stage after induction of anticipated pharmacoresistant epilepsy by kainate.

PMID- 21199576
TI  - Does osteoporosis predispose falls? A study on obstacle avoidance and balance
      confidence.
AB  - BACKGROUND: Osteoporosis is associated with changes in balance and physical
      performance and has psychosocial consequences which increase the risk of falling.
      Most falls occur during walking; therefore an efficient obstacle avoidance
      performance might contribute to a reduction in fall risk. Since it was shown that
      persons with osteoporosis are unstable during obstacle crossing it was
      hypothesized that they more frequently hit obstacles, specifically under
      challenging conditions. METHODS: Obstacle avoidance performance was measured on a
      treadmill and compared between persons with osteoporosis (n = 85) and the
      comparison group (n = 99). The obstacle was released at different available
      response times (ART) to create different levels of difficulty by increasing time
      pressure. Furthermore, balance confidence, measured with the short ABC
      questionnaire, was compared between the groups. RESULTS: No differences were
      found between the groups in success rates on the obstacle avoidance task (p =
      0.173). Furthermore, the persons with osteoporosis had similar levels of balance
      confidence as the comparison group (p = 0.091). The level of balance confidence
      was not associated with the performance on the obstacle avoidance task (p =
      0.145). CONCLUSION: Obstacle avoidance abilities were not impaired in persons
      with osteoporosis and they did not experience less balance confidence than the
      comparison group. These findings imply that persons with osteoporosis do not have
      an additional risk of falling because of poorer obstacle avoidance abilities.

PMID- 21199577
TI  - MTML-msBayes: approximate Bayesian comparative phylogeographic inference from
      multiple taxa and multiple loci with rate heterogeneity.
AB  - BACKGROUND: MTML-msBayes uses hierarchical approximate Bayesian computation
      (HABC) under a coalescent model to infer temporal patterns of divergence and gene
      flow across codistributed taxon-pairs. Under a model of multiple codistributed
      taxa that diverge into taxon-pairs with subsequent gene flow or isolation, one
      can estimate hyper-parameters that quantify the mean and variability in
      divergence times or test models of migration and isolation. The software uses
      multi-locus DNA sequence data collected from multiple taxon-pairs and allows
      variation across taxa in demographic parameters as well as heterogeneity in DNA
      mutation rates across loci. The method also allows a flexible sampling scheme:
      different numbers of loci of varying length can be sampled from different taxon
      pairs. RESULTS: Simulation tests reveal increasing power with increasing numbers
      of loci when attempting to distinguish temporal congruence from incongruence in
      divergence times across taxon-pairs. These results are robust to DNA mutation
      rate heterogeneity. Estimating mean divergence times and testing simultaneous
      divergence was less accurate with migration, but improved if one specified the
      correct migration model. Simulation validation tests demonstrated that one can
      detect the correct migration or isolation model with high probability, and that
      this HABC model testing procedure was greatly improved by incorporating a summary
      statistic originally developed for this task (Wakeley's PsiW). The method is
      applied to an empirical data set of three Australian avian taxon-pairs and a
      result of simultaneous divergence with some subsequent gene flow is inferred.
      CONCLUSIONS: To retain flexibility and compatibility with existing bioinformatics
      tools, MTML-msBayes is a pipeline software package consisting of Perl, C and R
      programs that are executed via the command line. Source code and binaries are
      available for download at http://msbayes.sourceforge.net/ under an open source
      license (GNU Public License).

PMID- 21199578
TI  - The impact of audit and feedback on nodal harvest in colorectal cancer.
AB  - BACKGROUND: Adequate nodal harvest (>= 12 lymph nodes) in colorectal cancer has
      been shown to optimize staging and proposed as a quality indicator of colorectal
      cancer care. An audit within a single health district in Nova Scotia, Canada
      presented and published in 2002, revealed that adequate nodal harvest occurred in
      only 22% of patients. The goal of this current study was to identify factors
      associated with adequate nodal harvest, and specifically to examine the impact of
      the audit and feedback strategy on nodal harvest. METHODS: This population-based
      study included all patients undergoing resection for primary colorectal cancer in
      Nova Scotia, Canada, from 01 January 2001 to 31 December 2005. Linkage of the
      provincial cancer registry with other databases (hospital discharge, physician
      claims data, and national census data) provided clinicodemographic, diagnostic,
      and treatment-event data. Factors associated with adequate nodal harvest were
      examined using multivariate logistic regression. The specific interaction between
      year and health district was examined to identify any potential effect of
      dissemination of the previously-performed audit. RESULTS: Among the 2,322
      patients, the median nodal harvest was 8; overall, 719 (31%) had an adequate
      nodal harvest. On multivariate analysis, audited health district (p < 0.0001),
      year (p < 0.0001), younger age (p < 0.0001), non-emergent surgery (p < 0.0001),
      more advanced stage (p = 0.008), and previous cancer history (p = 0.03) were
      associated with an increased likelihood of an adequate nodal harvest. Interaction
      between year and audited health district was identified (p = 0.006) such that the
      increase in adequate nodal harvest over time was significantly greater in the
      audited health district. CONCLUSIONS: Improvements in colorectal cancer nodal
      harvest did occur over time. A published audit demonstrating suboptimal nodal
      harvest appeared to be an effective knowledge translation tool, though more so
      for the audited health district, suggesting a potentially beneficial effect of
      audit and feedback strategies.

PMID- 21199579
TI  - Factors associated with mortality in patients with drug-susceptible pulmonary
      tuberculosis.
AB  - BACKGROUND: Tuberculosis is a leading cause of death worldwide, yet the
      determinants of death are not well understood. We sought to determine risk
      factors for mortality during treatment of drug-susceptible pulmonary tuberculosis
      under program settings. METHODS: Retrospective chart review of patients with drug
      susceptible tuberculosis reported to the San Francisco Tuberculosis Control
      Program from 1990-2001. RESULTS: Of 565 patients meeting eligibility criteria, 37
      (6.6%) died during the study period. Of 37 deaths, 12 (32.4%) had tuberculosis
      listed as a contributing factor. In multivariate analysis controlling for follow
      up time, four characteristics were independently associated with mortality: HIV
      co-infection (HR = 2.57, p = 0.02), older age at tuberculosis diagnosis (HR =
      1.52 per 10 years, p = 0.001); initial sputum smear positive for acid fast
      bacilli (HR = 3.07, p = 0.004); and experiencing an interruption in tuberculosis
      therapy (HR = 3.15, p = 0.002). The association between treatment interruption
      and risk of death was due to non-adherence during the intensive phase of
      treatment (HR = 3.20, p = 0.001). The median duration of treatment interruption
      did not differ significantly in either intensive or continuation phases between
      those who died and survived (23 versus 18 days, and 37 versus 29 days,
      respectively). No deaths were directly attributed to adverse drug reactions.
      CONCLUSIONS: In addition to advanced age, HIV and characteristics of advanced
      tuberculosis, experiencing an interruption in anti-tuberculosis therapy,
      primarily due to non-adherence, was also independently associated with increased
      risk of death. Improving adherence early during treatment for tuberculosis may
      both improve tuberculosis outcomes as well as decrease mortality.

PMID- 21199580
TI  - Cathepsin B: a potential prognostic marker for inflammatory breast cancer.
AB  - BACKGROUND: Inflammatory breast cancer (IBC) is the most aggressive form of
      breast cancer. In non-IBC, the cysteine protease cathepsin B (CTSB) is known to
      be involved in cancer progression and invasion; however, very little is known
      about its role in IBC. METHODS: In this study, we enrolled 23 IBC and 27 non-IBC
      patients. All patient tissues used for analysis were from untreated patients.
      Using immunohistochemistry and immunoblotting, we assessed the levels of
      expression of CTSB in IBC versus non-IBC patient tissues. Previously, we found
      that CTSB is localized to caveolar membrane microdomains in cancer cell lines
      including IBC, and therefore, we also examined the expression of caveolin-1 (cav
      1), a structural protein of caveolae in IBC versus non-IBC tissues. In addition,
      we tested the correlation between the expression of CTSB and cav-1 and the number
      of positive metastatic lymph nodes in both patient groups. RESULTS: Our results
      revealed that CTSB and cav-1 were overexpressed in IBC as compared to non-IBC
      tissues. Moreover, there was a significant positive correlation between the
      expression of CTSB and the number of positive metastatic lymph nodes in IBC.
      CONCLUSIONS: CTSB may initiate proteolytic pathways crucial for IBC invasion.
      Thus, our data demonstrate that CTSB may be a potential prognostic marker for
      lymph node metastasis in IBC.

PMID- 21199581
TI  - The advantages and disadvantages of horizontal gene transfer and the emergence of
      the first species.
AB  - BACKGROUND: Horizontal Gene Transfer (HGT) is beneficial to a cell if the
      acquired gene confers a useful function, but is detrimental if the gene has no
      function, if it is incompatible with existing genes, or if it is a selfishly
      replicating mobile element. If the balance of these effects is beneficial on
      average, we would expect cells to evolve high rates of acceptance of horizontally
      transferred genes, whereas if it is detrimental, cells should reduce the rate of
      HGT as far as possible. It has been proposed that the rate of HGT was very high
      in the early stages of prokaryotic evolution, and hence there were no separate
      lineages of organisms. Only when the HGT rate began to fall, would lineages begin
      to emerge with their own distinct sets of genes. Evolution would then become more
      tree-like. This phenomenon has been called the Darwinian Threshold. RESULTS: We
      study a model for genome evolution that incorporates both beneficial and
      detrimental effects of HGT. We show that if rate of gene loss during genome
      replication is high, as was probably the case in the earliest genomes before the
      time of the last universal common ancestor, then a high rate of HGT is
      favourable. HGT leads to the rapid spread of new genes and allows the build-up of
      larger, fitter genomes than could be achieved by purely vertical inheritance. In
      contrast, if the gene loss rate is lower, as in modern prokaryotes, then HGT is,
      on average, unfavourable. CONCLUSIONS: Modern cells should therefore evolve to
      reduce HGT if they can, although the prevalence of independently replicating
      mobile elements and viruses may mean that cells cannot avoid HGT in practice. In
      the model, natural selection leads to gradual improvement of the replication
      accuracy and gradual decrease in the optimal rate of HGT. By clustering genomes
      based on gene content, we show that there are no separate lineages of organisms
      when the rate of HGT is high; however, as the rate of HGT decreases, a tree-like
      structure emerges with well-defined lineages. The model therefore passes through
      a Darwinian Threshold.

PMID- 21199582
TI  - Different responses to oxidized low-density lipoproteins in human polarized
      macrophages.
AB  - BACKGROUND: Oxidized low-density lipoprotein (oxLDL) uptake by macrophages plays
      an important role in foam cell formation. It has been suggested the presence of
      heterogeneous subsets of macrophage, such as M1 and M2, in human atherosclerotic
      lesions. To evaluate which types of macrophages contribute to atherogenesis, we
      performed cDNA microarray analysis to determine oxLDL-induced transcriptional
      alterations of each subset of macrophages. RESULTS: Human monocyte-derived
      macrophages were polarized toward the M1 or M2 subset, followed by treatment with
      oxLDL. Then gene expression levels during oxLDL treatment in each subset of
      macrophages were evaluated by cDNA microarray analysis and quantitative real-time
      RT-PCR. In terms of high-ranking upregulated genes and functional ontologies, the
      alterations during oxLDL treatment in M2 macrophages were similar to those in
      nonpolarized macrophages (M0). Molecular network analysis showed that most of the
      molecules in the oxLDL-induced highest scoring molecular network of M1
      macrophages were directly or indirectly related to transforming growth factor
      (TGF)-beta1. Hierarchical cluster analysis revealed commonly upregulated genes in
      all subset of macrophages, some of which contained antioxidant response elements
      (ARE) in their promoter regions. A cluster of genes that were specifically
      upregulated in M1 macrophages included those encoding molecules related to
      nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-kappaB)
      signaling pathway. Quantitative real-time RT-PCR showed that the gene expression
      of interleukin (IL)-8 after oxLDL treatment in M2 macrophages was markedly lower
      than those in M0 and M1 cells. HMOX1 gene expression levels were almost the same
      in all 3 subsets of macrophages even after oxLDL treatment. CONCLUSIONS: The
      present study demonstrated transcriptional alterations in polarized macrophages
      during oxLDL treatment. The data suggested that oxLDL uptake may affect TGF-beta1
      and NF-kappaB-mediated functions of M1 macrophages, but not those of M0 or M2
      macrophages. It is likely that M1 macrophages characteristically respond to
      oxLDL.

PMID- 21199583
TI  - Sources, perceived usefulness and understanding of information disseminated to
      families who entered home quarantine during the H1N1 pandemic in Victoria,
      Australia: a cross-sectional study.
AB  - BACKGROUND: Voluntary home quarantine of cases and close contacts was the main
      non-pharmaceutical intervention used to limit transmission of pandemic (H1N1)
      2009 influenza (pH1N1) in the initial response to the outbreak of the disease in
      Australia. The effectiveness of voluntary quarantine logically depends on
      affected families having a clear understanding of what they are being asked to
      do. Information may come from many sources, including the media, health
      officials, family and friends, schools, and health professionals. We report the
      extent to which families who entered home quarantine received and used
      information on what they were supposed to do. Specifically, we outline their
      sources of information; the perceived usefulness of each source; and associations
      between understanding of recommendations and compliance. METHODS: Cross-sectional
      survey administered via the internet and computer assisted telephone interview to
      families whose school children were recommended to go into home quarantine
      because they were diagnosed with H1N1 or were a close contact of a case. The
      sample included 314 of 1157 potentially eligible households (27% response rate)
      from 33 schools in metropolitan Melbourne. Adjusting for clustering within
      schools, we describe self-reported 'understanding of what they were meant to do
      during the quarantine period'; source of information (e.g. health department) and
      usefulness of information. Using logistic regression we examine whether
      compliance with quarantine recommendations was associated with understanding and
      the type of information source used. RESULTS: Ninety per cent understood what
      they were meant to do during the quarantine period with levels of understanding
      higher in households with cases (98%, 95% CI 93%-99% vs 88%, 95% CI 84%-91%, P =
      0.006). Over 87% of parents received information about quarantine from the
      school, 63% from the health department and 44% from the media. 53% of households
      were fully compliant and there was increased compliance in households that
      reported that they understood what they were meant to do (Odds Ratio 2.27, 95% CI
      1.35-3.80). CONCLUSIONS: It is critical that public health officials work closely
      with other government departments and media to provide clear, consistent and
      simple information about what to do during quarantine as high levels of
      understanding will maximise compliance in the quarantined population.

PMID- 21199584
TI  - A randomised controlled trial to compare opt-in and opt-out parental consent for
      childhood vaccine safety surveillance using data linkage: study protocol.
AB  - BACKGROUND: The Vaccine Assessment using Linked Data (VALiD) trial compared opt
      in and opt-out parental consent for a population-based childhood vaccine safety
      surveillance program using data linkage. A subsequent telephone interview of all
      households enrolled in the trial elicited parental intent regarding the return or
      non-return of reply forms for opt-in and opt-out consent. This paper describes
      the rationale for the trial and provides an overview of the design and methods.
      METHODS/DESIGN: Single-centre, single-blind, randomised controlled trial (RCT)
      stratified by firstborn status. Mothers who gave birth at one tertiary South
      Australian hospital were randomised at six weeks post-partum to receive an opt-in
      or opt-out reply form, along with information explaining data linkage. The
      primary outcome at 10 weeks post-partum was parental participation in each arm,
      as indicated by the respective return or non-return of a reply form (or via
      telephone or email response). A subsequent telephone interview at 10 weeks post
      partum elicited parental intent regarding the return or non-return of the reply
      form, and attitudes and knowledge about data linkage, vaccine safety, consent
      preferences and vaccination practices. Enrolment began in July 2009 and 1,129
      households were recruited in a three-month period. Analysis has not yet been
      undertaken. The participation rate and selection bias for each method of consent
      will be compared when the data are analysed. DISCUSSION: The VALiD RCT represents
      the first trial of opt-in versus opt-out consent for a data linkage study that
      assesses consent preferences and intent compared with actual opting in or opting
      out behaviour, and socioeconomic factors. The limitations to generalisability are
      discussed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
      ACTRN12610000332022.

PMID- 21199596
TI  - Simultaneous inferior and middle meatus antrostomies in the treatment of the
      severely diseased maxillary sinus.
AB  - BACKGROUND: Although the majority of the maxillary pathology can be eradicated
      through the enlarged middle meatus antrostomy (MMA), some patients have extensive
      disease that is difficult to cope with. The aim of this study was to estimate the
      usefulness of simultaneous middle and inferior meatal antrostomies (MIMAs) in
      cases with severely diseased maxillary sinus by comparing the subjective and
      objective outcomes between patients that underwent MIMA and those who experienced
      maxillary clearance through conventional MMA. METHODS: A prospective study was
      performed on patients with nasal polyps and severely diseased maxillary sinus
      (Lund-Mackay CT score = 2). All diseased sinuses were addressed with the same
      endoscopic sinus surgery technique; the only difference consisted of the
      management of the maxillary sinus: 34 patients underwent MIMAs and in 38 cases
      maxillary sinus was approached solely through the MMA. After 12 months of follow
      up, outcomes consisted of the visual analog scale (VAS) for the main symptoms,
      the Lund-Mackay and maxillary sinus endoscopic scores, and the percent of
      airspace occluded by inflammatory mucosal thickening on CT. RESULTS: Subjective
      improvement in VAS scores for nasal obstruction, facial pain, and nasal
      discharge/retronasal drip was significantly better in the MIMA group. The mucosal
      thickening as expressed by the CT scan and maxillary endoscopic score was
      significantly reduced in the MIMA group. CONCLUSION: The MIMA technique is useful
      for removing severe disease that can not be reached through the MMA and yields
      both better subjective and better objective outcomes. The additional inferior
      antrostomy most likely improves drainage and ventilation in the postoperative
      period.

PMID- 21199597
TI  - Cancer and the environment: Ten topics in environmental cancer epidemiology in
      Canada.
AB  - This Chronic Diseases in Canada supplement is a compilation of literature reviews
      by scientific experts. It was initiated as follow-up to the Green Plan, the
      federal government's environmental agenda in the 1990s. In recognizing that
      Canadians are concerned about the environment and its relationship to their
      health, this document attempts to address some of these concerns in relation to
      cancer by reviewing and summarizing the epidemiological literature for ten
      environmental exposures, and highlighting future research needs. The topics
      include three types of radiation exposure (ultraviolet, radon and electromagnetic
      (powerfrequency electromagnetic fields)), three classes of chemical exposure
      (organochlorines, disinfection by-products, and pesticides), two types of air
      pollution (environmental tobacco smoke and outdoor air pollution), and two
      industrial sources (pulp and paper milling, and metal mining and processing).
      This publication is intended to provide a base of information for researchers
      interested in environmental cancer epidemiology and to assist with the
      formulation of research priorities. The ten topics reviewed here were selected
      because concern about them has been expressed or because they involve known
      animal carcinogens. Complete elimination of exposures to carcinogens in the
      environment, synthetic or natural, is not technically feasible if cancer can
      potentially occur at any level of exposure (i.e., the linear non-threshold
      theory). Consequently, it is important to have an operational concept of safety
      which is more practical than that of zero risk. Such an approach uses the concept
      of acceptable or essentially negligible risk to determine the exposure levels at
      which carcinogens are regulated. Acceptable risk has been defined as one that is
      "so small, whose consequences are so slight, or whose associated benefits
      (perceived or real) are so great that persons or groups in society are willing to
      take or be subjected to that risk". The level of risk where remedial action is
      recommended will vary according to the "agent or process being regulated, the
      economic and social costs and benefits and technology factors". In accordance
      with the system used by the International Agency for Research on Cancer (IARC) to
      assess the strength of the evidence for human carcinogenicity, the ten exposures
      reviewed here can be grouped into three broad categories, with some exposures
      occupying more than one and the first category-human carcinogens-should be
      subdivided. Tables 1-4 refer to these categories. For many of the exposures
      discussed here, ongoing etiological research awaits methods development,
      particularly in exposure assessment.

PMID- 21199598
TI  - Radon.
AB  - Radon is a radioactive gas that emanates from uranium-bearing soil and porous
      rock. Although radon is most highly concentrated in areas of high uranium
      concentration, the presence of trace amounts of uranium in most ground sources
      means that all humans are exposed to radon to some degree. Radon migrates out of
      soil and rock into the surrounding air, resulting in accumulation in poorly
      ventilated or closed areas. Such areas represent the primary environments in
      which humans are exposed to radioactivity from radon to experience detrimental
      health effects. There is no convincing evidence that any cancers other than lung
      cancer are associated with exposure to radon. There is, on the other hand,
      consistent evidence of a substantially elevated risk of lung cancer among
      Canadians exposed to radon in certain occupational settings, particularly uranium
      mining. While the combined evidence for a positive association between
      residential radon exposure and lung cancer is less compelling, the inherent
      methodological difficulties in mounting such studies may render it impossible for
      any single study to detect the relationship more conclusively. The best available
      evidence to date from pooled analyses indicates a positive, but weak association
      between residential radon and lung cancer risk. Residential radon is of critical
      importance because it is ubiquitous; a small excess risk that may exist in
      relation to radon exposures encountered in a residential setting translates into
      the potential for a far greater number of excess cancers in the general
      population than does exposure of a relatively small number of miners, even though
      the latter may be exposed to much higher levels of ionizing radiation.
      Fortunately, a number of techniques are available to homeowners to reduce radon
      concentrations in their homes.

PMID- 21199599
TI  - Ultraviolet radiation.
AB  - The major source of ultraviolet radiation is solar radiation or sunlight.
      However, exposure to artificial sources particularly through tanning salons is
      becoming more important in terms of human health effects, as use of these
      facilities by young people, has increased. The International Agency for Research
      on Cancer has noted that there is sufficient evidence from studies in animals and
      in man to establish ultraviolet radiation as a human carcinogen. Skin cancer has
      been the most commonly studied cancer site with respect to UV radiation. The
      nature and timing of sun exposure appear to be important determinants of both the
      degree of risk and the type of skin cancer. Cutaneous malignant melanoma and
      basal cell cancer are much more strongly related to measures of intermittent
      ultraviolet exposure (particularly those of childhood or adolescence) than to
      measures of cumulative exposure. In contrast, squamous cell cancer is more
      strongly related to constant or cumulative sun exposure. Lip cancer is causally
      related to lifetime sun exposure. It has been estimated that solar ultraviolet
      radiation accounts for approximately 93 percent of skin cancers and about half of
      lip cancers. This translates to approximately 4,500 life-threatening cancers
      (cutaneous malignant melanoma) per year in Canada, as well as 65,000 less serious
      cancers (basal cell cancer, squamous cell cancer and lip cancer). Appropriate
      clothing use, care not to sunburn and judicious use of sunscreens could prevent
      at least half of these and save approximately 450 lives per year. In addition,
      physician and public education programs can significantly increase the proportion
      of melanomas diagnosed early. Lesions that have not yet penetrated deeply are
      associated with a mortality rate of less than five percent. Several recent
      studies suggest a possible inverse relationship between ultraviolet radiation
      exposure and risk of non-Hodgkin lymphoma, colon, breast and prostate cancer, and
      investigators have speculated that this might be due to the higher serum levels
      of vitamin D stimulated by high lifetime sun exposure. Further, studies conducted
      within cohorts using stored pre-diagnostic serum suggest that those with high
      levels of vitamin D have lower incidence rates of a number of malignancies,
      particularly colon cancer. However, since serum vitamin D levels can be raised
      through the use of supplements without increasing risk for skin lip and other
      known UV-related cancers, changes to health policy with regard to exposure are
      not merited at this point. Further research is needed in this area.

PMID- 21199600
TI  - Electric and magnetic fields at power frequencies.
AB  - Exposures to electric and magnetic fields are among the most ubiquitous exposures
      that the Canadian population experiences. Sources of electric and magnetic field
      exposures may be occupational or residential and include proximity to certain
      types of electrical equipment, transmission and distribution power lines as well
      as appliance use. The early studies of children tended toward a consistent
      association between risks for leukemia and brain cancer and residential proximity
      to power lines having high wire configuration. More recent studies-and studies
      which have attempted to improve upon the measurement of exposure by using
      calculated fields, point-in-time or personal monitoring-have been inconsistent,
      with some suggesting increased risk and others not. Occupational exposures have
      suggested an increase in risk for leukemia, and to a lesser extent brain cancer
      and Non-Hodgkin lymphoma. However, studies of residential exposures and cancer in
      adults generally have suggested no effect. Laboratory work has been unable to
      demonstrate a biological mechanism which might explain the epidemiological
      findings. In spite of extensive efforts over the past 20 years and many expert
      reviews, it has been difficult to reach consensus regarding the carcinogenic
      effects of electric and magnetic fields. Exposure assessment has proven to be
      complex, and agreement on the relevant exposure metric has not yet been obtained.
      There is justification to question whether point-in-time measures in homes are
      appropriate indices of the relevant etiological exposure, as they fail to account
      for changes over time, peak exposures or time-varying fields. Nevertheless, it is
      probably desirable to err on the side of caution in not placing too much weight
      on the inconsistencies. The IARC has classified EMF as a "possible carcinogen"
      which refers to the circumstances where there is limited evidence of
      carcinogenicity in humans and inadequate evidence in experimental animals. The
      IARC review indicated limited evidence for the carcinogenicity of extremely low
      frequency magnetic fields in relation to childhood leukemia at high level
      exposure in the residential environment (average residential magnetic field
      strength >0.4 MUT). Even higher levels of exposure in the occupational
      environment may increase the risk of leukemia in adults.

PMID- 21199601
TI  - Cancer risk associated with pulp and paper mills: a review of occupational and
      community epidemiology.
AB  - Pulp and paper mills use a variety of chemical substances potentially hazardous
      to human health. Compounds of both short- and long-term toxicological
      significance are found in workplaces, air emissions, and water effluent. In this
      paper we evaluate the body of published literature on cancer associated with
      working in pulp and paper mills as well as in surrounding communities. Multiple
      comparisons, questionable statistical power, and the absence of individual
      exposure assessments have resulted in non-corroborative findings over the years.
      However, a new generation of study sophistication, international in scale and
      coordinated by the International Agency for Research on Cancer (IARC), has
      catalogued tens of thousands of exposure measurements made at a large number of
      work stations within the pulp and paper industry, allowing for greatly improved
      individual-level exposure assessments. This approach reduces non-differential
      misclassification of exposure, increasing the power of these studies to detect
      exposure disease relationships, especially for rarer cancers. While the ability
      to associate specific chemical exposures with cancer outcomes in the large IARC
      multinational cohort may yet help to resolve the status of some of the many
      chemicals not currently classifiable as to their carcinogenicity by IARC, this
      effort has, to date, not added significantly to knowledge. Of the three studies
      they have published to date, one involved a well-established carcinogen
      (asbestos) and another involved a mixture containing probable carcinogens
      (volatile organochlorines). While the asbestos study is somewhat unremarkable for
      finding an association with pleural cancer in the expected direction, the
      volatile organochlorine study may be most notable for failing to find an
      association between volatile organochlorine exposure and liver cancer, non
      Hodgkin's lymphoma, or esophageal cancer, as some previous studies had found.
      Nonetheless, given the known hazards and the potential for both environmental and
      human exposure by any of a number of pathways, vigilance on the part of
      governments for regulation and for ongoing workplace and environmental monitoring
      remains a health imperative.

PMID- 21199602
TI  - Gold, nickel and copper mining and processing.
AB  - Ore mining occurs in all Canadian provinces and territories except Prince Edward
      Island. Ores include bauxite, copper, gold, iron, lead and zinc. Workers in metal
      mining and processing are exposed, not only to the metal of interest, but also to
      various other substances prevalent in the industry, such as diesel emissions, oil
      mists, blasting agents, silica, radon, and arsenic. This chapter examines cancer
      risk related to the mining of gold, nickel and copper. The human carcinogenicity
      of nickel depends upon the species of nickel, its concentration and the route of
      exposure. Exposure to nickel or nickel compounds via routes other than inhalation
      has not been shown to increase cancer risk in humans. As such, cancer sites of
      concern include the lung, and the nasal sinus. Evidence comes from studies of
      nickel refinery and leaching, calcining, and sintering workers in the early half
      of the 20th century. There appears to be little or no detectable risk in most
      sectors of the nickel industry at current exposure levels. The general population
      risk from the extremely small concentrations detectable in ambient air are
      negligible. Nevertheless, animal carcinogenesis studies, studies of nickel
      carcinogenesis mechanisms, and epidemiological studies with quantitative exposure
      assessment of various nickel species would enhance our understanding of human
      health risks associated with nickel. Definitive conclusions linking cancer to
      exposures in gold and copper mining and processing are not possible at this time.
      The available results appear to demand additional study of a variety of potential
      occupational and non-occupational risk factors.

PMID- 21199603
TI  - Air pollution.
AB  - Toxic air pollutants are continuously released into the air supply. Various
      pollutants come from chemical facilities and small businesses, such as automobile
      service stations and dry cleaning establishments. Others, such as nitrogen
      oxides, carbon monoxide and other volatile organic chemicals, arise primarily
      from the incomplete combustion of fossil fuels (coal and petroleum) and are
      emitted from sources that include car exhausts, home heating and industrial power
      plants. Pollutants in the atmosphere also result from photochemical
      transformations; for example, ozone is formed when molecular oxygen or nitrogen
      interacts with ultraviolet radiation. An association between air pollution
      exposure and lung cancer has been observed in several studies. The evidence for
      other cancers is far less conclusive. Estimates of the population attributable
      risk of cancer has varied substantially over the last 40 years, reflecting the
      limitations of studies; these include insufficient information on confounders,
      difficulties in characterizing associations due to a likely lengthy latency
      interval, and exposure misclassification. Although earlier estimates were less
      than one percent, recent cohort studies that have taken into account some
      confounding factors, such as smoking and education amongst others, suggest that
      approximately 3.6% of lung cancer in the European Union could be due to air
      pollution exposure, particularly to sulphate and fine particulates. A separate
      cohort study estimated 5-7% of lung cancers in European never smokers and ex
      smokers could be due to air pollution exposure. Therefore, while cigarette
      smoking remains the predominant risk factor, the proportion of lung cancers
      attributable to air pollution may be higher than previously thought. Overall,
      major weaknesses in all air-pollution-and-cancer studies to date have been
      inadequate characterization of long-term air pollution exposure and imprecise or
      no measurements of covariates. It has only been in the last decade that
      measurements to PM2.5 become more widely available. A key weakness of many
      studies is using fixed-site monitoring data and assuming everyone in a region had
      the same exposure. This ignores spatial variability, and does not take into
      account how individuals' exposures differ with pollution sources inside, outside,
      both at work, home and elsewhere. More recent efforts to model indicators of
      vehicular traffic, and residential distances to major roads and highway can allow
      for some of this spatial variability to be better controlled for. However, this
      still does not take into account differences in activity patterns. If the effect
      is small, these biases will compromise the ability to detect an association. In
      most situations, the resulting estimates tend to be biased toward the null (i.e.,
      no effect). For misclassification of exposure the inability to adequately control
      for confounding variables may cause bias in either direction. Recent improvements
      in statistical methodology use measurements at fixed sites combined with
      residential histories to estimate individuals' cumulative exposures. They also
      recognize measurement errors associated with covariates in the analysis to
      improve estimates of effects. Other challenges include the fact that measurements
      of exposure and confounders can change over time and long term data are needed
      due to the anticipated latency interval between harmful exposures and development
      of cancer.

PMID- 21199604
TI  - Leptospirosis: a Toll road from B lymphocytes.
AB  - Leptospirosis is a widespread zoonosis caused by Leptospira interrogans, a
      pathogen transmitted by asymptomatic infected rodents. Leptospiral lipoproteins
      and lipopolysaccharide (LPS) have been shown to stimulate murine cells via Toll
      like receptors (TLRs) 2 and 4. Host defense mechanisms remain obscure, although
      TLR4 has been associated with clearing Leptospira. In a recent study, we showed
      that in response to Leptospira infection, double (TLR2 and TLR4) knock-out (DKO)
      mice unexpectedly developed TLR-independent pro-inflammatory responses, and
      rapidly died from severe hepatic and renal failure. Subsequent analysis of
      chimeric and transgenic mice identified B-cells as the crucial lymphocyte subset
      responsible for the clearance of Leptospira, initially through the production of
      specific TLR4-dependent immunoglobulin M (IgM), directed against the LPS of
      Leptospira, and subsequently through specific IgG production, which is impaired
      in DKO mice. We also identified the protective, tissue-compartmentalized,
      TLR2/TLR4-mediated production of interferon-gamma?(IFN-gamma) by B- and T
      lymphocytes. Overall, our recent findings demonstrate that TLR2 and TLR4 both
      play a key role in the early control of leptospirosis, and constitute the first
      line of defense against Leptospira, confirming previous in vitro data showing
      that both LPS and lipoprotein play a crucial role in cell activation. However, if
      this first line of defense is by-passed, Leptospira can induce a deleterious
      inflammation in the target organs, and this does not rely on TLR activation.

PMID- 21199605
TI  - Cutaneous melanoma: Taiwan experience and literature review.
AB  - Malignant melanoma is a rare disease in Taiwan with an incidence rate of
      0.65/100,000. Excessive exposure to ultraviolet radiation is not associated with
      most Taiwanese melanoma cases. Acral lentiginous melanoma comprises 58% of
      cutaneous melanoma. Advanced disease is seen in 50% of cases. Surgery, including
      resection of the primary melanoma, sentinel lymph nodes that may harbor
      microscopic metastasis, clinically abnormal lymph nodes, and selected distant
      metastases, is the most important treatment. Lymphatic mapping and sentinel lymph
      node biopsy has changed the clinical stage in 22.2% of our patients. Adjuvant
      high-dose interferon significantly prolongs progression-free survival. However,
      its use in Taiwan is limited by its substantial toxicity. The prognosis of
      metastatic disease remains poor with a median survival of 12 months. In the past,
      chemotherapy alone was the most common treatment modality for metastatic disease.
      Recently biochemotherapy has been more commonly utilized to treat patients with
      metastatic melanoma.

PMID- 21199606
TI  - Changes in high-density lipoprotein and homeostasis model assessment of insulin
      resistance in medicated schizophrenic patients and healthy controls.
AB  - BACKGROUND: This study intended to simultaneously investigate the relationships
      between high-density lipoprotein (HDL) and homeostasis model assessment of
      insulin resistance (HOMA-IR) in medicated schizophrenic patients vs healthy
      controls. METHODS: During a 1-year period, we recruited 37 medicated
      schizophrenic patients and 30 healthy controls. Metabolic syndrome-related
      biomarkers including insulin and lipid profiles were enzymatically determined.
      RESULTS: An analysis of covariance (ANCOVA) with BMI adjustment revealed that the
      patients had significantly lower HDL levels than the healthy controls (p =
      0.017). ANCOVA with age adjustment revealed that the patients had significantly
      higher fasting insulin levels than the healthy controls (p = 0.034). In addition,
      in comparison with the healthy controls, the patients had higher mean serum
      levels of triglycerides, low-density lipoprotein, and total cholesterol as well
      as higher HOMA-IR values. However, there were no significant differences in any
      marker in the ANCOVA analysis after adjustment for age or BMI. CONCLUSION: We
      found lower HDL and higher insulin levels in medicated schizophrenic patients
      than in healthy controls.

PMID- 21199607
TI  - Correlations between expression of epidermal growth factor receptor (EGFR),
      phosphorylated EGFR, cyclooxygenase-2 and clinicopathological variables and
      treatment outcomes in nasopharyngeal carcinomas.
AB  - BACKGROUND: To evaluate immunoexpression of epidermal growth factor receptor
      (EGFR), phosphorylated EGFR (pEGFRTyr1068), and cyclooxygenase-2 (COX-2) and
      analyze their prognostic utility in nasopharyngeal carcinomas (NPC). METHODS: We
      used a retrospective review of charts and tissue specimens. The immunoexpression
      levels of EGFR, pEGFRTyr1068, and COX-2 were semiquantitatively assessed by the H
      score method for 170 NPC samples from patients treated with radiotherapy (RT)
      alone. RESULTS: The ranges of immunohistochemical H-scores were 0-510 (median
      225) for EGFR, 0-395 (median 25) for pEGFRTyr1068, and 0-460 (median 170) for COX
      2. None of these 3 markers were significantly associated with one another,
      clinicopathological factors, or the rates of locoregional control (LRC), distant
      metastasis-free survival (DMFS), or overall survival (OS). In multivariate
      analysis, the independent adverse prognosticators were T-stage for LRC, N-stage
      for DMFS, and T-stage, N-stage, and age > 60 years for OS. CONCLUSIONS:
      Immunoexpression levels of EGFR, pEGFRTyr1068, and COX-2 were not related to
      clinicopathological variables and not predictive of outcomes of NPC patients
      treated with RT alone.

PMID- 21199608
TI  - Brain reorganization after bilateral arm training and distributed constraint
      induced therapy in stroke patients: a preliminary functional magnetic resonance
      imaging study.
AB  - BACKGROUND: Bilateral arm training (BAT) and constraint-induced therapy (CIT)
      have shown beneficial effects in improving motor control and function of the
      upper extremities (UE) for patients with stroke. Thus far, no study has directly
      investigated the relative effects of BAT versus CIT on brain reorganization. This
      study compared the effects of BAT with distributed CIT (dCIT) on brain
      reorganization and motor function in 6 stroke patients. METHODS: In a pre-post
      randomized controlled trial, 6 stroke patients received BAT (intensive bilateral
      simultaneous and symmetrical training) or dCIT (restraint of the unaffected UE
      combined with intensive training of the affected UE) for a period of 3 weeks, 5
      days per week. Functional magnetic resonance imaging (fMRI) examination and 3
      clinical measures (Fugl-Meyer Assessment, Action Research Arm Test, and Motor
      Activity Log) were administered before and after the intervention. RESULTS: After
      intervention, patients showed varied patterns of fMRI changes and improved motor
      function. Two well-recovered patients, one from each group, showed large
      increases in bilateral hemisphere activation, especially in the ipsilesional
      hemisphere during affected hand movement and in the contralesional hemisphere
      during unaffected hand movement. During bilateral elbow movement, 3 of the 4 BAT
      patients showed increased bilateral cerebellum activation, especially in the left
      cerebellum, whereas 2 dCIT patients showed decreased cerebellar activation.
      CONCLUSIONS: The findings of this preliminary research revealed that neuroplastic
      changes after stroke motor rehabilitation may be specific to the intervention.
      Further research using a larger sample and more complex fMRI tasks is warranted
      to validate the findings.

PMID- 21199609
TI  - Feasibility and safety of a transradial approach in intervention for chronic
      total occlusion of coronary arteries: a single-center experience.
AB  - BACKGROUND: The transradial approach for cardiac catheterization has become
      popular; however, its application in percutaneous coronary intervention (PCI) for
      chronic total occlusion (CTO) has rarely been reported. This study examines the
      feasibility and safety of this approach for performing PCI for CTO lesions.
      METHOD: We retrospectively evaluated 419 consecutive patients who underwent PCI
      for CTO lesions between February 1998 and December 2003 in our hospital; a
      transradial artery approach was used in 400 patients and a transfemoral artery
      approach in 19. RESULTS: The baseline clinical characteristics were similar in
      the 2 patient groups. The transradial group had more de novo lesions (76% vs
      47.37%, p = 0.012), fewer in-stent restenotic lesions (11.75% vs 36.84%, p =
      0.006) and smaller guiding catheters (p < 0.001) than the transfemoral group.
      There was no statistical difference in the procedure success rates (69.25% and
      78.95%, p = 0.369) between the 2 groups. The incidence of major complications,
      including death, Q wave myocardial infarction, and emergency coronary artery
      bypass surgery, was similar in the 2 groups. CONCLUSIONS: The transradial
      approach for PCI can be a feasible choice for a CTO lesion. If this approach
      fails because of poor back up support from the guiding catheter, the transfemoral
      approach can be attempted with a larger guiding catheter.

PMID- 21199610
TI  - A Preliminary study of the development, validity, and reliability of a caregiver
      questionnaire for the health-related quality of life in children with cerebral
      palsy.
AB  - BACKGROUND: In Taiwan, there is no disease-specific instrument to measure the
      health-related quality of life (HRQL) in children with cerebral palsy (CP). The
      goal of this preliminary study was to develop and test the validity and
      reliability of a caregiver questionnaire for HRQL in children with CP (CQ-HRQL
      CP). METHODS: The CQ-HRQL-CP included 4 dimensions, motor ability, pain and
      emotion, interaction and participation, and satisfaction and expectation. The
      questions were modified based on the content validity index (CVI). A purposive
      sampling of 45 parents of children with CP completed tests of the item
      discriminant validity and internal consistency. Twenty of these parents were
      randomly recruited for further testing of the test-retest reliability. RESULTS:
      The CVI of individual items and dimensions was 0.86~1. With regard to the item
      discriminant validity, items which correlated more strongly with other dimensions
      than with their own dimensions were deleted. The adjusted Cronbach's coefficient
      value was 0.87~0.99. The test-retest reliability, evaluated using an intraclass
      correlation coefficient (ICC(3,1)), was 0.86~0.99 for each dimension.
      CONCLUSIONS: The content validity, item discriminant validity, internal
      consistency, and test-retest reliability of this new CQ-HRQL-CP were acceptable.
      Further study of the concurrent validity of the CQ-HRQL-CP is needed.

PMID- 21199611
TI  - Atrial size independently correlates with the development of paroxysmal atrial
      fibrillation in patients with sick sinus syndrome.
AB  - BACKGROUND: Atrial fibrillation arises in 20-30% of patients with sick sinus
      syndrome, increasing the risk of systemic embolization and mortality. The aim of
      this study was to examine the clinical determinants of development of paroxysmal
      atrial fibrillation in sick sinus syndrome patients before implantation of a
      pacemaker. METHODS: This case-control survey involved 144 patients (mean age +/-
      SD age: 72 +/- 9 years) in whom implantation of a transvenous permanent pacemaker
      was planned for sick sinus syndrome. Patients were classified into two groups,
      patients with (n = 71) and without (n = 73) a history of paroxysmal atrial
      fibrillation before implantation. Clinical characteristics and echocardiographic
      parameters were analyzed. RESULTS: The peri-implant right atrial area and left
      atrial area were significantly larger in patients with, than those without,
      paroxysmal atrial fibrillation. Multiple logistic regression analysis identified
      that the size of the left atrial area independently correlated with the
      development of atrial fibrillation: each 1 cm2 increase in left atrial area
      corresponded to a 44% increase in risk (odds ratio = 1.44 [1.22, 1.71]; p <
      0.001). CONCLUSIONS: The left atrial size independently correlates with the
      development of paroxysmal atrial fibrillation in sick sinus syndrome patients
      before pacemaker implantation.

PMID- 21199612
TI  - Short- to medium-term outcomes of radial head replacement arthroplasty in
      posttraumatic unstable elbows: 20 to 70 months follow-up.
AB  - BACKGROUND: The radial head is considered the main stabilizer of the elbow when
      the medial collateral ligament and lateral ulnar collateral ligament have been
      compromised. Radial head replacement (RHR) is indicated for patients with
      irreparable or non-united radial head fractures associated with elbow stiffness
      or instability. The present study aimed to analyze the clinical results after
      treatment with titanium radial head prostheses, repair of torn soft tissue
      constraints, and early mobilization of the elbow. METHODS: From 2002 to 2008, 13
      patients with radial head fractures were included. RHR arthroplasty was performed
      primarily for irreparable fractures in 10 patients and secondarily for radial
      head fracture nonunion in 3. All patients were followed-up clinically and
      radiographically for a mean of 38 months (range, 20 to 70 months). RESULTS: On
      the basis of Mayo Elbow Performance Scores, 8 patients had excellent results; 3,
      good results; and 2, fair results. No patient had elbow instability after RHR.
      Two patients had elbow stiffness 6 months after RHR and underwent surgical
      intervention for contracture release. None of the prostheses were removed because
      of loosening or infection. CONCLUSION: Treatment of irreparable radial head
      fractures with a modular titanium radial head prosthesis and soft-tissue
      reconstruction yields satisfactory results. Early mobilization of the elbow is
      important for the restoration of elbow range of motion and function.

PMID- 21199613
TI  - Percutaneous trigeminal nerve radiofrequency rhizotomy guided by computerized
      tomography with three-dimensional image reconstruction.
AB  - BACKGROUND: Percutaneous radiofrequency trigeminal rhizotomy offers high rates of
      complete pain relief for classic idiopathic trigeminal neuralgia. When performed
      under fluoroscopy, it may cause anxiety for an inexperienced neurosurgeon owing
      to lack of familiarity with the regional anatomy, lack of reliable landmarks on
      fluoroscopy, and perceived risks associated with inadvertent puncture of
      neurovascular structures near the foramen ovale. The purpose of this study is to
      describe a new procedure to maximize patient security and shorten operative time.
      METHODS: From January 2006 to May 2009, 79 patients with trigeminal neuralgia
      underwent computerized tomography (CT)-guided percutaneous radiofrequency
      trigeminal rhizotomy under local anesthesia at Chang Gung Memorial Hospital.
      These patients included 22 men and 57 women, whose ages ranged from 36 to 88
      years. The authors analyzed the use of CT with three-dimensional image
      reconstruction for the guidance of rhizotomy needle placement to determine
      possible difficulties during surgery and to predict the outcome of surgery.
      RESULTS: The surgical outcome of CT-guided trigeminal rhizotomy was good in 63
      (80%, 95% confidence interval [CI] 69.2-88.0%) of the 79 patients with more than
      90% (95% CI 87.5-93.7%) pain relief. The outcomes did not differ from those of
      the fluoroscopy-guided procedures. However, the median time for adequate
      rhizotomy needle placement in the foramen ovale was reduced in the CT-guided
      compared with that in fluoroscopy-guided procedure (14 minutes and 40 minutes,
      respectively; p < 0.001) and the intra-operative discomfort of the patients was
      also decreased. There were no intra-operative failures. CONCLUSION: For
      percutaneous trigeminal rhizotomy, three-dimensional image reconstruction
      provides for precise placement of the rhizotomy needle in a safe and timely
      manner, which improves patient comfort and shortens operative time.

PMID- 21199614
TI  - Cost feasibility of a pre-checking medical tourism system for U.S. patients
      undertaking joint replacement surgery in Taiwan.
AB  - BACKGROUND: Medical tourism is a relatively recent global economic and political
      phenomenon that has assumed increasing importance for developing countries,
      particularly in Asia. In fact, Taiwan possesses a niche for developing medical
      tourism because many hospitals provide state-of-the-art medicine in all
      disciplines and many doctors are trained in the United States (US). Among the
      most common medical procedures outsourced, joint replacements such as total knee
      replacement (TKR) and total hip replacement (THR) are two surgeries offered to US
      patients at a lower cost and shorter waiting time than in the US. METHODS: This
      paper proposed a pre-checking medical tourism system (PCMTS) and evaluated the
      cost feasibility of recruiting American clients traveling to Taiwan for joint
      replacement surgery. Cost analysis was used to estimate the prime costs for each
      stage in the proposed PCMTS. Sensitivity analysis was implemented to examine how
      different pricings for medical checking and a surgical operation (MC&SO) and
      recovery, can influence the surplus per patient considering the PCMTS. Finally,
      the break-even method was adopted to test the tradeoff between the sunk costs of
      investment in the PCMTS and the annual surplus for participating hospitals.
      RESULTS: A novel business plan was built showing that pre-checking stations in
      medical tourism can provide post-operative care and recovery follow-up.
      Adjustable pricing for hospital administrators engaged in the PCMTS consisted of
      two main costs: US$3,700 for MC&SO and US$120 for the hospital stay. Guidelines
      for pricing were provided to maximize the annual surplus from this plan with
      different number of patients participating in PCMTS. The maximal profit margin
      from each American patient undertaking joint surgery is about US$24,315.
      CONCLUSIONS: Using cost analysis, this article might be the first to evaluate the
      feasibility of PCMTS for joint replacement surgeries. The research framework in
      this article is applicable when hospital administrators evaluate the feasibility
      of outsourced medical procedures other than TKR and THR.

PMID- 21199615
TI  - Mixed epithelial and stromal tumor of the kidney--a case report.
AB  - A 45-year-old woman had gross hematuria without flank pain for two weeks. She
      visited our hospital and a renal echo showed a heterogenous mass on the left
      kidney. Abdominal computed tomography showed a multicystic tumor, about 7 cm, on
      the left renal pelvis and the proximal ureter. The tumor was enhanced after
      contrast injection. Ureteroscopy showed an intraluminal polypoid tumor. Cystic
      renal cell carcinoma or urothelial carcinoma was suspected preoperatively. We
      performed a hand-assisted laparoscopic nephroureterectomy, and the post-operative
      course was uneventful. The pathology report demonstrated that the tumor was
      composed of an admixture of stroma and flattened to cuboidal urothelium. The
      tumor stromal cells expressed both estrogen and progesterone receptors, and no
      malignant cells were found. There has been no recurrence or deterioration of the
      patient's renal function since surgery. We suggest keeping in mind the diagnosis
      of mixed epithelial and stromal tumor of the kidney when encountering
      perimenopausal women with renal cystic tumors.

PMID- 21199616
TI  - A Surgery-first approach in surgical-orthodontic treatment of mandibular
      prognathism--a case report.
AB  - The conventional approach in orthodontic surgery treatment of dentofacial
      anomalies requires a varied period of pre-surgical orthodontic treatment. This
      presurgical period is considered to be important for adequate surgical treatment
      and stable results. This period is usually long bothersome for patients because
      dental decompensation is required and there is consequent deterioration of
      aesthetics and function, especially in cases of skeletal Class III occlusion. At
      Chang Gung Craniofacial Center, a surgery-first approach (SFA), i.e. minimal pre
      surgical orthodontics, is one of the treatment choices for Class III patients. In
      this report, we present a 19-year-old man with mandibular prognathism, an
      anterior open bite and severe dental crowding treated with SFA. The patient
      received orthognathic surgery a week after bracing of the teeth. The operation
      and recovery were uneventful as well as the following orthodontic treatment. The
      total treatment time was only four months, much shorter than with the
      conventional approach. The patient benefitted from immediate improvement of the
      facial profile after surgery, and a much shorter total treatment, and the results
      were not compromised. We believe in selected cases, SFA is a good and effective
      treatment alternative.

PMID- 21199618
TI  - [Percutaneous coronary intervention requires heart centers and volume].

PMID- 21199617
TI  - [Open access to Ugeskriftet's articles can undermine the fundament of publishing
      research articles].

PMID- 21199619
TI  - [Tattoos in a dermatological perspective].
AB  - Tattoos are very popular. Widely used standard industrial pigments are used. The
      field lacks basic knowledge concerning pigments, epidemiology and complications
      such as allergy, granulomas, skin cancer and foreign body reactions. The risks
      associated with laser treatment are unknown. Studies have suggested that some
      degradation products are carcinogenic. The field lacks formal regulation at
      national and European levels and EU had to give up attempts to control the area
      in 2003 because of lack of knowledge in the field.

PMID- 21199620
TI  - [Efforts to increase the response to mailed questionnaires].
AB  - INTRODUCTION: Great effort should be made to ensure that as many subjects as
      possible reply when using mailed questionnaires. It has been shown that including
      a monetary reward or sending a short form increases the number of replies. The
      purpose of the study was to determine whether this is true also in Scandinavia.
      MATERIAL AND METHODS: Questionnaires were sent to 200 women and 200 men in each
      age decade of 20-29 years and older. Totally, 2,000 long and 800 short
      questionnaires were mailed - 200 letters included 50 NOK (Norwegian kroner), 500
      letters included 10 NOK, and 1,000 letters included 1 NOK. At the time of mailing
      5 NOK was worth approximately 1 USD. The remainder served as controls. Block
      randomization ensured an even distribution of the various rewards and long and
      short forms in each age decade and sex. RESULTS: After 11 weeks 59% had returned
      the short form and 54% the long form (p = 0.03). Replies were received from 54%
      of the control subjects, from 53% of subjects who had received 1 NOK, from 58% of
      subjects who had received 10 NOK, and from 74% of subjects who had received 50
      NOK (p < 0.001). CONCLUSION: A short form is returned statistically significantly
      more often than a long form, but the difference is only moderate. A monetary
      reward increases the rate of reply considerably also in Scandinavia. The sum sent
      must be fairly high to have effect.

PMID- 21199621
TI  - [New classification of acute pancreatitis].
AB  - The course of acute pancreatitis is in the initial phase dominated by a systemic
      inflammatory response, later by local complications. A new classification defines
      three specific types of pancreatitis: 1) interstitial oedematous pancreatitis and
      2) necrotizing pancreatitis with pancreatic parenchymal necrosis, or 3)
      peripancreatic necrosis alone. The classification also defines four types of
      collections: 1) Acute peripancreatic fluid collection, 2) pseudocyst, 3) acute
      post-necrotic collection, and 4) walled-off necrosis. This article summarizes the
      terminology of the revised Atlanta classification.

PMID- 21199622
TI  - [Chronic pain after groin hernia repair].
AB  - Multiple mechanisms are responsible for persistent postherniotomy pain, including
      preoperative pain hypersensitivity, other chronic pain states and intraoperative
      nerve injury. Currently, the primary preventive techniques are intraoperative
      nerve identification/sparing in open surgery or use of laparoscopic surgery with
      non-fixed mesh. The choice between pharmacological intervention and re
      exploration is debatable. A centralisation of the Danish patients with regard to
      evaluation and treatment is proposed.

PMID- 21199623
TI  - [Charles Bonnet syndrome and visual hallucination].
AB  - Charles Bonnet syndrome is characterized by vivid, complex and recurrent visual
      hallucinations occurring in psychologically normal people. Though not related to
      any specific eye condition, it commonly affects visually impaired elderly persons
      and is thus an important differential diagnosis to many conditions which cause
      visual hallucinations. Patients usually retain insight into the unreal nature of
      their hallucination. The hallucinatory experiences are generally not distressing,
      but patients may fear impending insanity. There is no specific treatment for this
      condition which in most cases is self-limiting.

PMID- 21199624
TI  - [Hallucinations in vision impairment].
AB  - A 79-year-old female had vision loss due to wet age-related macular degeneration,
      corneal endothelial dystrophy with corneal oedema and cataract. She subsequently
      began hallucinating and saw imaginary vehicles, bridges, trees and houses on the
      road while driving (Charles Bonnet syndrome (CBS)). The hallucinations caused
      anxiety and distress. Her general practitioner started anti-anxiety therapy with
      no significant effect. Anti-vascular endothelial growth factor therapy and a
      corneal transplantation improved her visual acuity, decreased the frequency of
      hallucinations and resulted in complete remission of the her anxiety. Thus,
      vision-improving treatment of eye disease may decrease CBS-associated anxiety.

PMID- 21199625
TI  - [Erythema multiforme-like reaction to para-phenylenediamine].
AB  - A case of a 15 year-old girl who developed an erythema multiforme-like reaction
      to para-phenylenediamine (PPD) after Henna tattoos is described. The patient was
      treated successfully with oral prednisolone and highly potent topical
      corticosteroids. The patient developed a long-lasting post-inflammatory
      hyperpigmentation. Potential hyperreactive response was prevented by applying the
      PPD patch for only 30 minutes, but still there was a significantly positive
      reaction. This case highlights the need to ban the use of para-phenylenediamine
      and its derivates in dyes.

PMID- 21199626
TI  - [Picture of the month: foreign body removal].

PMID- 21199627
TI  - Television depictions about dermatology and skin diseases in Seinfeld.
AB  - The iconic television situation comedy Seinfeld frequently referenced
      dermatologists and topics involving the integument, using satire for comedic
      effect. However, selecting satire to portray an already misunderstood and unknown
      subject matter may perpetuate incorrect public beliefs and stereotypes about
      those with skin diseases and diminish cultural sensitivity towards people who
      have dermatologic conditions and their caregivers.

PMID- 21199628
TI  - Review of home phototherapy.
AB  - BACKGROUND: Outpatient phototherapy is a safe, effective, and low-cost treatment
      modality for moderate to severe psoriasis. Barriers to outpatient phototherapy
      including patient inconvenience, patient co-pays, decreased physician
      compensation, and insurance disincentive structures have led to decreased use and
      underutilization of phototherapy. Home phototherapy can potentially overcome many
      of the barriers associated with outpatient treatment but is not widely used
      because of concerns over safety and efficacy, lack of resident and physician
      education, and lack of insurance coverage. PURPOSE: The purpose of this study is
      to review the use of phototherapy with emphasis on the safety, efficacy, and
      practical use of home phototherapy. METHODS: A comprehensive Pubmed literature
      search was done using the keywords NB-UVB, narrowband UVB, BB-UVB, broadband UVB,
      PUVA, psoralen and UVA, UVA, history of phototherapy, mechanism of phototherapy,
      phototherapy in dermatology, home phototherapy, and phototherapy for psoriasis.
      All relevant articles were reviewed. CONCLUSIONS: Home NB-UVB phototherapy can be
      as safe, effective, and cost-effective as outpatient phototherapy. Further, home
      UVB is more convenient for patients, has higher patient satisfaction, and a lower
      treatment burden compared to outpatient phototherapy. Home NB-UVB should be
      considered as a treatment option for patients eligible for phototherapy.

PMID- 21199629
TI  - Frictional lichenified dermatosis from prolonged use of a computer mouse: Case
      report and review of the literature of computer-related dermatoses.
AB  - Despite the increasing reliance on computers and the associated health risks,
      computer-related dermatoses remain under-represented in the literature. This term
      collectively refers to four groups of cutaneous pathologies: 1) allergic contact
      dermatitis from exposure to certain chemicals in computer accessories, 2) various
      friction-induced hand lesions resulting from prolonged computer use, 3) erythema
      ab igne from placement of the laptop on the skin, and 4) "screen dermatitis" from
      excessive exposure to visual display terminals (VDTs). Within this review we also
      present a case of a friction-induced lichenified dermatosis in the dominant wrist
      of a 24-year-old female that was caused by excessive use of her computer mouse.
      More importantly, we review the literature of all previously reported cases of
      computer-related dermatoses, so as to promote recognition and appropriate
      management by both patients and physicians.

PMID- 21199630
TI  - Multiple myeloma presenting as a novel mucocutaneous eruption.
AB  - A 71-year-old woman presented with exquisitely tender mucosal erosions, a diffuse
      polymorphous eruption, and night sweats. Workup revealed multiple myeloma with a
      monoclonal IgG-kappa paraprotein in the serum. Her severe oral involvement was
      suggestive of paraneoplastic pemphigus, but direct and indirect
      immunofluorescence tests were negative. A skin biopsy showed spongiosis and a
      sparse perivascular lymphocytic infiltrate, with occasional CD8-positive
      lymphocytes in the epidermis. Her lesions improved with intravenous immune
      globulin. Immunohistochemical staining on the formalin-fixed biopsy specimen was
      strongly positive for IgG and IgG-kappa in an epidermal "chicken-wire" pattern,
      but negative for IgG-lambda. Her pulmonary tissue stained negative for IgG-kappa,
      suggesting clinical relevance of the myeloma paraprotein in her epidermis. To our
      knowledge, this is the first report of a multiple myeloma patient with such an
      eruption.

PMID- 21199631
TI  - Primary cutaneous marginal zone B-cell lymphoma: An atypical case.
AB  - Primary cutaneous marginal zone B-cell lymphoma (PCMZBCL) is an entity with an
      indolent behavior, which clinically appears as erythematous papules, nodules, or
      plaques, solitary or multiple, on the trunk or upper extremities. It has been
      associated with autoimmune diseases and infections. We present the case of a 77
      year-old woman with an atypical PCMZBCL with extracutaneous spread and associated
      autoimmune hemolytic anemia.

PMID- 21199632
TI  - Primary cutaneous marginal zone lymphoma as a complication of radiation therapy:
      Case report and review.
AB  - BACKGROUND: The occurrence of primary cutaneous B-cell lymphoma at the site of
      radiation therapy is exceptional. We report herein the case of a primary
      cutaneous marginal zone lymphoma arising at the site of radiotherapy for breast
      cancer. METHODS/RESULTS: A seventy-year-old woman was diagnosed in 2005 with an
      invasive ductal carcinoma of the left breast, which was treated with surgery,
      adjuvant chemotherapy, and radiation therapy. Three years later she developed
      several cutaneous nodules on her left breast, followed by similar lesions on her
      back. Histologic, immunohistochemistry, and molecular findings were consistent
      with the diagnosis of cutaneous marginal zone lymphoma. Physical examination was
      otherwise negative, as well as mammography, total body CT, bone marrow biopsy,
      and Borrelia serology. CONCLUSIONS: To our knowledge, this is the first published
      case of primary cutaneous marginal zone lymphoma occurring at the site of
      radiotherapy. Cutaneous surveillance is proposed from the first year after
      irradiation in order to detect new primary malignancies, including this rare
      cutaneous neoplasm.

PMID- 21199633
TI  - Fibro-osseous pseudotumor of the digit: Presentation as an enlarging erythematous
      cutaneous nodule.
AB  - Fibro-osseous pseudotumor of the digit is an unusual ossifying fibro
      proliferative lesion. The current case is a 54-year-old woman who presented with
      an enlarging reddish nodule on the distal aspect of her left big toe. Excision
      biopsy was performed and the histopathology featured a dermal-centered lesion
      composed of osteoblast-rimmed bony trabculae lying amidst fibrovascular stroma.
      This entity resembles and may be within the spectrum of myositis ossificans, the
      prototype post-traumatic reactive fibro-osseous proliferation, although the
      latter is typically more proximally located and features a zonation pattern on
      histopathology. The distinguishing features from other pathological differential
      diagnoses, such as subungual exostosis and extraskeletal osteosarcoma, are
      discussed. The growth is considered benign and local recurrence following
      complete excision is unusual.

PMID- 21199635
TI  - Laugier-Hunziker syndrome: A case report and review of the literature.
AB  - Laugier-Hunziker syndrome (LHS) is a rare acquired disorder characterized by
      diffuse macular hyperpigmentation of the oral mucosa and, at times, longitudinal
      melanonychia. Although LHS is considered a benign disease with no systemic
      manifestations or malignant potential, it is important to rule out other
      mucocutaneous pigmentary disorders that do require medical management. Prompt
      clinical recognition also averts the need for excessive and invasive procedures
      and treatments. To date, only four cases have been reported in the United States.
      We present a 77-year-old man who had clinical features typical of LHS and we then
      provide a review of the literature on LHS and its mimickers.

PMID- 21199634
TI  - Hypocomplementemic urticarial vasculitis in mixed connective tissue disease.
AB  - Urticarial vasculitis is characterized clinically by urticaria-like skin lesions
      and histologically by leukocytoclastic vasculitis. It may be idiopathic or
      associated with various conditions such as infections, hematologic disorders,
      drugs, and connective tissue diseases, primarily systemic lupus erythematosus; an
      association with mixed connective tissue disease (MCTD) has rarely been reported.
      We present a case of hypocomplementemic urticarial vasculitis in a patient with
      MCTD that responded to hydroxychloroquine after a period of corticosteroid
      dependence.

PMID- 21199636
TI  - Porokeratosis of Mibelli: Successful treatment with 5 percent topical imiquimod
      and topical 5 percent 5-fluorouracil.
AB  - Porokeratosis of Mibelli (PM) is a clonal disorder of keratinization. It
      clinically presents with one or more annular plaques with central atrophy and
      elevated keratotic borders. With a 7.5 percent risk of malignancy, PM should be
      treated to prevent transformation into squamous cell carcinoma, Bowen disease, or
      basal cell carcinoma. Multiple treatment options are available, however, there is
      not one universally effective treatment. We describe the successful treatment of
      porokeratosis of Mibelli of the left calf in an 83-year-old man with topical 5
      percent imiquimod and topical 5 percent 5-fluorouracil.

PMID- 21199637
TI  - Nicolau livedoid dermatitis following intramuscular benzathine penicillin
      injection.
AB  - We report the case of a 64-year-old male presenting with a rapidly enlarging
      painful violaceous plaque in the left buttock and posterior thigh, following a
      gluteal intramuscular injection of benzathine penicillin. Associated urinary
      incontinence and lower left limb paresis were consistent with sciatic and lower
      sacral nerve damage, as confirmed by electromyography. Additional underlying
      muscular damage was observed in ultrasound and computer tomodensitometry scans
      and supported by high serum levels of creatine kinase and lactate dehydrogenase.
      Aggressive treatment was performed with fluid expansion, intravenous steroid
      bolus, vasodilators and anticoagulation, resulting in slow improvement of
      cutaneous and muscular lesions. However, no significant effect was observed on
      neurologic dysfunction after 6 months of regular neuromuscular rehabilitation.
      Nicolau Livedoid Dermatitis is a rare and potentially fatal condition showing
      variable levels of tissue impairment and unpredictable course and prognosis.
      Specific treatment is not consensual and the efficacy of any particular treatment
      remains to be established.

PMID- 21199638
TI  - Disseminated porokeratosis of Mibelli: A case report.
AB  - Porokeratosis is a disorder of clonal hyperproliferation of keratinocytes with
      several different clinical manifestations. Cutaneous lesions vary in their
      appearance and distribution. All variants share the distinguishing cornoid
      lamella on histopathological examination. We present an unusual case of
      disseminated porokeratosis of Mibelli in an immunocompetent patient.

PMID- 21199639
TI  - Letter: Fixed drug eruption caused by the Japanese herbal drug kakkonto.
AB  - Herbal drugs are now widely used throughout the world. The general public tends
      to believe these agents to be safe because of their natural origin; thus, they
      are used frequently. However, the side effects of many of these potent chemicals
      may be significant. Several cases of fixed drug eruption (FDE) caused by herbal
      drugs have been reported. We herein report a case of FDE caused by kakkonto.

PMID- 21199640
TI  - Letter: Cerebriform intradermal nevus presenting as secondary cutis verticis
      gyrata.
AB  - Cutis verticis gyrata is a rare skin condition characterized by ridges and
      furrows resembling the surface of the brain. It can be considered as a
      manifestation of a variety of diverse causes such as cerebriform intradermal
      nevus. We report a 48-year-old man with cerebriform and soft folds on the left
      parietal and temporal areas. Histology showed solitary or clusters of nevus cells
      in the dermis. The diagnosis of cerebriform intradermal nevus was confirmed.

PMID- 21199641
TI  - Letter: It is Dermatosis neglecta.
AB  - The case presented in the article "Severe retention hyperkeratosis occurring with
      Susac syndrome" in October 2010 of DOJ (16:10) is very dramatic. Although it was
      implied in the article, the authors did not state that this is actually
      Dermatosis neglecta, the same entity reported by Poskitt et al 15 years ago. The
      description of the case in the article, histopathology, mechanism of
      pathogenesis, and treatment are consistent with Dermatosis neglecta, only with a
      different name.

PMID- 21199642
TI  - Letter: Localized cutaneous reaction to intramuscular vitamin K in a patient with
      acute fatty liver of pregnancy.
AB  - Vitamin K1 is frequently used in the treatment and prevention of
      hypoprothrombinemia and hemorrhagic disease of the newborn. It also serves as an
      antidote to anticoagulants. Erythematous, indurated, pruritic plaques uncommonly
      occur in adults after intramuscular injection with vitamin K1. We present a case
      of a localized cutaneous reaction to intramuscular vitamin K1 in a peripartum
      patient with acute fatty liver of pregnancy. The history and clinical
      presentation of our case is presented with a discussion of the pathogenesis
      pathogenesis of vitamin K1 and available treatment for this condition.

PMID- 21199643
TI  - The advantages of low-density lipoproteins in the cryopreservation of bull semen.
AB  - Egg low-density lipoprotein (LDL) was added at concentrations (w/v) of 7%, 8% or
      9% to the extenders used to freeze bull semen and its effects on seminal
      parameters and anti-oxidant activities of frozen-thawed sperm were assessed.
      Analysis of data showed that sperm exposed to 8% LDL exhibited the greatest
      percentages of sperm motility, acrosome integrity and membrane integrity,
      compared to the control which differed from the treatment groups by replacing LDL
      with 20% egg yolk (P<0.05). No difference was observed for membrane integrity
      between 8% and 9% LDL groups (P>0.05). The extender supplemented with LDL did not
      exhibit improvement in SOD levels. However, 8% LDL group favored the highest anti
      oxidant activities of CAT, GSH-Px and GSH in comparison to other groups (7%, 9%
      LDL and the control) (P<0.05). No difference was observed for CAT activity
      between 9% LDL and the control group. In conclusion, sperm cryopreserved in the
      extender containing 8% LDL in place of egg yolk exhibited the greatest
      percentages of post-thaw sperm motility, acrosome integrity and membrane
      integrity, in comparison with the control, and favored the highest anti-oxidant
      activities of CAT, GSH-Px and GSH in comparison with other groups. The
      replacement of egg yolk by LDL in the composition of extenders was beneficial for
      bull sperm cryopreservation.

PMID- 21199644
TI  - Melanocortins and body weight regulation: glucocorticoids, Agouti-related protein
      and beyond.
AB  - In the intervening three decades since Panksepp observed for the first time that
      centrally administered alpha-melanocyte stimulating hormone decreased food intake
      (Panksepp and Meeker, 1976), a wealth of data have accrued to firmly establish
      melanocortin signaling as a central regulator of food intake and fat mass.
      Advances in molecular biology have not only allowed detailed studies of
      spontaneously occurring obese mice with altered melanocortin signaling to be
      undertaken but also permitted the generation of a plethora of mouse models with
      precise perturbations at critical steps in the melanocortin system to finesse
      further the cellular and molecular architecture of relevant pathways. In this
      article we focus in upon a number of these mouse models which continue to help us
      tease apart the complexities of this critical system. Further, we review data on
      the important interaction between pro-opiomelanocortin derived peptides and the
      adrenal system and the relationship between agonist and antagonist peptides
      acting at central melanocortin receptors.

PMID- 21199645
TI  - Melanocortin MC4 receptor expression sites and local function.
AB  - The melanocortin MC(4) receptor plays an important role in energy metabolism, but
      also affects blood pressure, heart rate and erectile function. Localization of
      the receptors that fulfill these distinct roles is only partially known. Mapping
      of the melanocortin MC(4) receptor has been stymied by the absence of a
      functional antibody. Several groups have examined mRNA expression of the
      melanocortin MC(4) receptor in the rodent brain and transgenic approaches have
      also been utilized to visualize melanocortin MC(4) receptor expression sites
      within the brain. Ligand expression and binding studies have provided additional
      information on the areas of the brain where this elusive receptor is functionally
      expressed. Finally, microinjection of melanocortin MC(4) receptor ligands in
      specific nuclei has further served to elucidate the function of melanocortin
      MC(4) receptors in these nuclei. These combined approaches have helped link the
      anatomy and function of this receptor, such as the role of paraventricular
      hypothalamic nucleus melanocortin MC(4) receptor in the regulation of food
      intake. Intriguingly, however, numerous expression-sites have been identified
      that have not been linked to a specific receptor function such as those along the
      optic tract and olfactory tubercle. Further research is needed to clarify the
      function of the melanocortin MC(4) receptor at these sites.

PMID- 21199646
TI  - Melanocortin MC1 receptor in human genetics and model systems.
AB  - The melanocortin MC(1) receptor is a G-protein coupled receptor expressed in the
      melanocytes of the skin and hair and is known for its key role in the regulation
      of human pigmentation. Melanocortin MC(1) receptor activation after ultraviolet
      radiation exposure results in a switch from the red/yellow pheomelanin to the
      brown/black eumelanin pigment synthesis within cutaneous melanocytes; this
      pigment is then transferred to the surrounding keratinocytes of the skin. The
      increase in melanin maturation and uptake results in tanning of the skin,
      providing a physical protection of skin cells from ultraviolet radiation induced
      DNA damage. Melanocortin MC(1) receptor polymorphism is widespread within the
      Caucasian population and some variant alleles are associated with red hair
      colour, fair skin, poor tanning and increased risk of skin cancer. Here we will
      discuss the use of mouse coat colour models, human genetic association studies,
      and in vitro cell culture studies to determine the complex functions of the
      melanocortin MC(1) receptor and the molecular mechanisms underlying the
      association between melanocortin MC(1) receptor variant alleles and the red hair
      colour phenotype. Recent research indicates that melanocortin MC(1) receptor has
      many non-pigmentary functions, and that the increased risk of skin cancer
      conferred by melanocortin MC(1) receptor variant alleles is to some extent
      independent of pigmentation phenotypes. The use of new transgenic mouse models,
      the study of novel melanocortin MC(1) receptor response genes and the use of more
      advanced human skin models such as 3D skin reconstruction may provide key
      elements in understanding the pharmacogenetics of human melanocortin MC(1)
      receptor polymorphism.

PMID- 21199647
TI  - Implication of the melanocortin-3 receptor in the regulation of food intake.
AB  - The melanocortin system is well recognized to be involved in the regulation of
      food intake, body weight, and energy homeostasis. To probe the role of the MC(3)
      in the regulation of food intake, JRH322-18 a mixed MC(3) partial
      agonist/antagonist and MC(4) agonist tetrapeptide was examined in wild type (WT)
      and melanocortin 4 receptor (MC(4)) knockout mice and shown to reduce food intake
      in both models. In the wild type mice, 2.0 nmol of JRH322-18 statistically
      reduced food intake 4h post icv treatment into satiated nocturnally feeding wild
      type mice. The same dose in the MC(4)KO mice significantly reduced cumulative
      food intake 24h post treatment. Conditioned taste aversion as well as activity
      studies supports that the decreased food intake was not due to visceral illness.
      Since these studies resulted in loss-of-function results, the SHU9119 and agouti
      related protein (AGRP) melanocortin receptor antagonists were administered to
      wild type as well as the MC(3) and MC(4) knockout mice in anticipation of gain-of
      function results. The SHU9119 ligand produced an increase in food intake in the
      wild type mice as anticipated, however no effect was observed in the MC(3) and
      MC(4) knockout mice as compared to the saline control. The AGRP ligand however,
      produced a significant increase in food intake in the wild type as well as the
      MC(3) and MC(4) knockout mice and it had a prolonged affect for several days.
      These data support the hypothesis that the MC(3) plays a subtle role in the
      regulation of food intake, however the mechanism by which this is occurring
      remains to be determined.

PMID- 21199649
TI  - A comparative study of the structural organization of spheres derived from the
      adult human subventricular zone and glioblastoma biopsies.
AB  - Sphere forming assays have been useful to enrich for stem like cells in a range
      of tumors. The robustness of this system contrasts the difficulties in defining a
      stem cell population based on cell surface markers. We have undertaken a study to
      describe the cellular and organizational composition of tumorspheres, directly
      comparing these to neurospheres derived from the adult human subventricular zone
      (SVZ). Primary cell cultures from brain tumors were found to contain variable
      fractions of cells positive for tumor stem cell markers (CD133 (2-93%)/SSEA1 (3
      15%)/CXCR4 (1-72%)). All cultures produced tumors upon xenografting. Tumorspheres
      contained a heterogeneous population of cells, but were structurally organized
      with stem cell markers present at the core of spheres, with markers of more
      mature glial progenitors and astrocytes at more peripheral location.
      Ultrastructural studies showed that tumorspheres contained a higher fraction of
      electron dense cells in the core than the periphery (36% and 19%, respectively).
      Neurospheres also contained a heterogeneous cell population, but did not have an
      organization similar to tumorspheres. Although tumorspheres clearly display
      irregular and neoplastic cells, they establish an organized structure with an
      outward gradient of differentiation. We suggest that this organization is central
      in maintaining the tumor stem cell pool.

PMID- 21199648
TI  - Cardiovascular effects of melanocortins.
AB  - Melanocortins (MSH's) are three structurally related peptides derived from
      proopiomelanocortin. They regulate several physiologic functions including energy
      metabolism, appetite, and inflammation. Recent work in rodents has also
      identified important effects of MSH's, particularly gamma-MSH, on sodium
      metabolism and blood pressure regulation. Normal rats and mice respond to a high
      sodium diet with an increase in the plasma concentration of gamma-MSH, and remain
      normotensive, while those with genetic or pharmacologic gamma-MSH deficiency
      become hypertensive on a high sodium diet. This hypertension is corrected by
      exogenous administration of the peptide. Mice lacking the gamma-MSH receptor (the
      melanocortin 3 receptor, Mc3r) also become hypertensive on a high sodium diet but
      remain so when administered gamma-MSH, and infusions of physiologic levels of the
      peptide stimulate urinary sodium excretion in normal rats and mice, but not in
      mice with deletion of Mc3r. The salt-sensitive hypertension in rodents with
      impaired gamma-MSH signaling appears due to stimulation of noradrenergic
      activity, since plasma noradrenaline is increased and the hypertension is rapidly
      corrected with infusion of the alpha-adrenoceptor antagonist phentolamine. In
      contrast to the antihypertensive property of physiologic levels of gamma-MSH,
      intravenous or intracerebroventricular injections of high levels of the peptide
      raise blood pressure. This occurs in mice lacking Mc3r, indicating an interaction
      with some other central receptor. Finally, the salt-sensitive hypertension in
      rodents with disruption of gamma-MSH signaling is accompanied by insulin
      resistance, an observation which offers a new window into the study of the
      association of salt-sensitive hypertension with insulin resistance and type II
      diabetes.

PMID- 21199650
TI  - Sex and acquired cofactors determine phenotypes of ferroportin disease.
AB  - BACKGROUND & AIMS: Ferroportin disease is characterized by iron overload. It has
      an autosomal-dominant pattern of inheritance and has been associated with
      mutations in the SLC40A1 gene, which encodes the cellular iron exporter
      ferroportin. Since the first description in 2001, about 30 mutations have been
      reported; the heterogeneity of ferroportin disease phenotypes has led to the
      hypothesis that the nature of the mutation affects the function of the protein in
      different ways. We studied genotypes and phenotypes of a large cohort of patients
      with ferroportin disease. METHODS: We studied clinical, biochemical, imaging,
      histologic, and genetic data from 70 affected subjects from 33 families with 19
      mutations. RESULTS: We found that ferroportin disease, at the time of diagnosis,
      has limited consequences in the absence of cofactors. Data indicated that
      transferrin saturation, which correlated with fibrosis and levels of alanine
      aminotransferase, might be a marker of disease severity. Although the study was
      performed in a large number of families, we observed incomplete penetrance and no
      correlation between genotypes and phenotypes. CONCLUSIONS: Members of families
      with ferroportin disease should be screened for biochemical parameters of iron
      metabolism as well as genotype to detect silent mutations that might cause
      disease with acquired or genetic cofactors. Patients should be followed up long
      term to identify potential complications of the disease.

PMID- 21199651
TI  - Inactivation of Brca2 promotes Trp53-associated but inhibits KrasG12D-dependent
      pancreatic cancer development in mice.
AB  - BACKGROUND & AIMS: Inherited mutations in the BRCA2 tumor suppressor have been
      associated with an increased risk of pancreatic cancer. To establish the
      contribution of Brca2 to pancreatic cancer we developed a mouse model of pancreas
      specific Brca2 inactivation. Because BRCA2-inactivating mutations cause defects
      in repair of DNA double-strand breaks that result in chromosomal instability, we
      evaluated whether Brca2 inactivation induced instability in pancreatic tissue
      from these mice and whether associated pancreatic tumors were hypersensitive to
      DNA damaging agents. METHODS: We developed mouse models that combined pancreas
      specific Kras activation and Trp53 deletion with Brca2 inactivation. Development
      of pancreatic cancer was assessed; tumors and nonmalignant tissues were analyzed
      for chromosomal instability and apoptosis. Cancer cell lines were evaluated for
      sensitivity to DNA damaging agents. RESULTS: In the presence of disrupted Trp53,
      Brca2 inactivation promoted the development of premalignant lesions and
      pancreatic tumors that reflected the histology of human disease. Cancer cell
      lines derived from these tumors were hypersensitive to specific DNA damaging
      agents. In contrast, in the presence of KrasG12D, Brca2 inactivation promoted
      chromosomal instability and apoptosis and unexpectedly inhibited growth of
      premalignant lesions and tumors. CONCLUSIONS: Trp53 signaling must be modified
      before inactivation of the Brca2 wild-type allele, irrespective of Kras status,
      for Brca2-deficient cells to form tumors.

PMID- 21199652
TI  - Intestinal DMT1 cotransporter is down-regulated by hepcidin via proteasome
      internalization and degradation.
AB  - BACKGROUNDS & AIMS: The mechanism by which hepcidin regulates iron export from
      macrophages has been well established and is believed to involve degradation of
      ferroportin. However, in the small intestine, hepcidin's mechanisms of action are
      not known. We studied human polarized intestinal (Caco-2/TC7) cells and mouse
      duodenal segments, ex vivo, to investigate the molecular mechanisms by which
      hepcidin down-regulates intestinal transepithelial iron transport. METHODS: Iron
      transport was analyzed using 55FeNTA. Expression of Divalent Metal Transporter 1
      (DMT1) and ferroportin was evaluated by reverse-transcription quantitative
      polymerase chain reaction and immunoblotting. Videomicroscopy analysis was
      performed on live cells that expressed either DMT1 or ferroportin fused to green
      fluorescent protein. RESULTS: In Caco-2/TC7 cells, physiologic doses of hepcidin
      (50-1000 nmol/L) inhibited transport of 55Fe in a dose-dependent manner; a half
      maximum effect was observed at 75-100 nmol/L. However, 200 nmol/L hepcidin
      induced a significant decrease in DMT1 protein expression but no change in
      ferroportin protein levels, unlike macrophages. This result was confirmed ex vivo
      in isolated duodenal segments: 200 nmol/L hepcidin induced a significant
      reduction in iron transport and DMT1 protein levels but no change in ferroportin
      levels. In Caco-2/TC7 cells, the effect of hepcidin on the DMT1 protein level was
      completely abolished in the presence of a proteasome inhibitor (MG-132); DMT1
      ubiquitination was induced by the addition of hepcidin. CONCLUSIONS: An acute
      increase in hepcidin concentration reduces intestinal iron absorption through
      ubiquitin-dependent proteasome degradation of DMT1.

PMID- 21199653
TI  - Inosine triphosphate protects against ribavirin-induced adenosine triphosphate
      loss by adenylosuccinate synthase function.
AB  - BACKGROUND & AIMS: Genetic variation of inosine triphosphatase (ITPA) causing an
      accumulation of inosine triphosphate (ITP) has been shown to protect patients
      against ribavirin (RBV)-induced anemia during treatment for chronic hepatitis C
      infection by genome-wide association study (GWAS). However, the biologic
      mechanism by which this occurs is unknown. METHODS: We examined whether ITP can
      be used by adenosine triphosphatase (ATPase) in human erythrocytes or recombinant
      human adenylosuccinate synthase (ADSS). RBV-induced adenosine triphosphate (ATP)
      reduction in erythrocytes was compared with the genetically determined low or
      normal activity of ITPA, leading respectively to high or normal ITP levels.
      RESULTS: Although ITP is not used directly by human erythrocyte ATPase, it can be
      used for ATP biosynthesis via ADSS in place of guanosine triphosphate (GTP). With
      RBV challenge, erythrocyte ATP reduction was more severe in the wild-type ITPA
      genotype than in the hemolysis protective ITPA genotype. This difference also
      remains after inhibiting adenosine uptake using nitrobenzylmercaptopurine
      riboside (NBMPR). Interestingly, the alleviation of ATP reduction by the
      hemolysis protective ITPA genotype was canceled by the ADSS inhibitor 6
      mercaptoethanol (6-MP). CONCLUSIONS: ITP confers protection against RBV-induced
      ATP reduction by substituting for erythrocyte GTP, which is depleted by RBV, in
      the biosynthesis of ATP. Because patients with excess ITP appear largely
      protected against anemia, these results confirm that RBV-induced anemia is due
      primarily to the effect of the drug on GTP and consequently ATP levels in
      erythrocytes.

PMID- 21199654
TI  - Modifying the protease, antiprotease pattern by elafin overexpression protects
      mice from colitis.
AB  - BACKGROUND & AIMS: Colonic tissues of patients with inflammatory bowel disease
      have been reported to have increased proteolytic activity, but no studies have
      clearly addressed the role of the balance between proteases and antiproteases in
      the pathogenesis of colitis. We investigated the role of Elafin, a serine
      protease inhibitor expressed by skin and mucosal surfaces in human inflammatory
      conditions, and the proteases neutrophil elastase (NE) and proteinase-3 (PR-3) in
      mice with colitis. METHODS: We studied mice with heterozygous disruptions in NE
      and PR-3, mice that express human elafin (an inhibitor of NE and PR-3), and naive
      mice that received intracolonic adenoviral vectors that express elafin.
      Trinitrobenzene sulfonic acid (TNBS) or dextran sodium sulphate (DSS) was used to
      induce colitis. Protease, cytokine levels, and NF-kappaB activity were measured
      in colons of mice. Caco-2 and HT29 cells were studied in assays for cytokine
      expression, permeability, and NF-kappaB activity. RESULTS: Elafin expression or
      delivery re-equilibrated the proteolytic balance in inflamed colons of mice. In
      mice given TNBS or DSS, transgenic expression of elafin or disruption of NE and
      PR-3 protected against the development of colitis. Similarly, adenoviral delivery
      of Elafin significantly inhibited inflammatory parameters. Elafin modulated a
      variety of inflammatory mediators in vitro and in vivo and strengthened
      intestinal epithelial barrier functions. CONCLUSIONS: The protease inhibitor
      Elafin prevents intestinal inflammation in mouse models of colitis and might be
      developed as a therapeutic agent for inflammatory bowel disease.

PMID- 21199655
TI  - The knockdown of the maternal estrogen receptor 2a (esr2a) mRNA affects embryo
      transcript contents and larval development in zebrafish.
AB  - In zebrafish, ovulated oocytes are loaded with maternal estrogen receptor 2a
      (esr2a) mRNA which is spread as granular and filamentous structures throughout
      the central ooplasm and is promptly relocated inside the blastodisc area at the 1
      cell stage (0.2h post-fertilization, hpf), as shown by in situ hybridization.
      This transcript is available for translation until its sharp decline from 4 to 8
      hpf, being replaced by low levels of zygotic esr2a mRNA mainly localized in the
      head region and around the yolk sac from 24 hpf until hatching at 48 hpf. To test
      the functional role of the maternal esr2a mRNA, 1- or 2-cell embryos were
      injected with 10.3 ng each of morpholino (MO) to knockdown translation (MO2
      esr2a) of both maternal and zygotic esr2a transcripts, with a missplicing MO (MO3
      esr2a) to effectively block post-transcriptionally the zygotic transcript alone,
      and with a non-specific MO-control. Treatment with MO2-esr2a increased apoptosis
      in embryos, especially in the brain, and caused severe malformations in 63% of 1
      5 dpf larvae, as compared to 10-11% in those treated with MO3-esr2a and MO
      control. Defects included body growth delay with curved shape, persistent yolk
      sac with reduced sub-intestinal veins and swollen yolk extension, abnormal brain
      and splanchnocranium development, smaller eyes and otic vesicles, pericardial
      oedema, uninflated swim bladder and rudimentary caudal fin with aberrant circular
      swimming. Affected larvae could survive for only 12-14 days. The MO2-esr2a
      phenotype was rescued with co-injection of 30 pg/embryo of mutated zebrafish
      esr2a mRNA encoding the full length of Esr2a, but containing eight silent
      mutations in the region recognised by MO2-esr2a. A lower dosage (15 pg) failed to
      recover mortality and abnormality. Raising the dosage to 60 and 90 pg increased
      abnormality, but not mortality, whereas with 120 pg both mortality and
      abnormality worsened, indicating a strict quantitative requirement of Esr2a. Co
      injection of an anti-p53 MO failed to rescue the MO2-esr2a phenotype, eliminating
      the possibility of off-target effects. Pangenomic microarray analysis revealed
      that 240 and 219 significantly expressed transcripts were up- and down-regulated,
      respectively, by maternal Esr2a protein deficiency in 8-hpf MO2-esr2a embryos.
      Also at 48 hpf, 162 and 120 presumably zygotic transcripts were up- and down
      regulated, respectively, but only 18 were in common with each of the 8-hpf sets.
      In total, the transcripts from 705 genes were affected by Esr2a knockdown. These
      findings suggest the involvement of maternal esr2a mRNA, presumably
      transactivated by maternal 17beta-estradiol stored in the oocyte from enveloping
      granulosa cells, in the epigenetic programming of zebrafish development.

PMID- 21199656
TI  - Circadian melatonin production develops faster in birds than in mammals.
AB  - The development of circadian rhythmicity of melatonin biosynthesis in the pineal
      gland starts during embryonic period in birds while it is delayed to the
      postnatal life in mammals. Daily rhythms of melatonin in isolated pinealocytes
      and in intact pineal glands under in vivo conditions were demonstrated during the
      last third of embryonic development in chick embryos, with higher levels during
      the dark (D) than during the light (L) phase. In addition to the LD cycle,
      rhythmic temperature changes with the amplitude of 4.5 degrees C can entrain
      rhythmic melatonin biosynthesis in chick embryos, with higher concentrations
      found during the low-temperature phase (33.0 vs 37.5 degrees C). Molecular
      clockwork starts to operate during the embryonic life in birds in line with the
      early development of melatonin rhythmicity. Expression of per2 and cry genes is
      rhythmic at least at day 16 and 18, respectively, and the circadian system
      operates in a mature-like manner soon after hatching. Rhythmic oscillations are
      detected earlier in the central oscillator (the pineal gland) than in the
      peripheral structures, reflecting the synchronization of individual cells which
      is necessary for detection of the rhythm. The early development of the circadian
      system in birds reflects an absence of rhythmic maternal melatonin which in
      mammals synchronizes physiological processes of offspring. Developmental
      consequences of modified development of circadian system for its stability later
      in development are not known and should be studied.

PMID- 21199657
TI  - Molecular characterization of structure and tissue distribution of chicken
      neurotensin receptor.
AB  - Neurotensin, a tridecapeptide, is distributed in a wide range of tissues and
      exhibits multiple functions through its receptors. Hitherto molecular
      characterization of the neurotensin receptor has been reported in mammalian,
      amphibian, and fish species but not in avian species. In this study, we cloned
      the cDNA encoding chicken neurotensin receptor from the duodenum and
      characterized its primary structure, biological activity and distribution in the
      gastrointestinal tract. The cDNA encoded a protein consisting of 399 amino acids
      that had significant overall sequence homology to other vertebrate neurotensin
      receptor 1 with higher extent in the seven transmembrane domains. Chicken
      neurotensin increased intracellular Ca(2+) concentrations in human embryonic
      kidney 293 cells transiently expressing the chicken neurotensin receptor 1. Real
      time PCR analysis showed that chicken neurotensin receptor 1 mRNA is expressed
      throughout the gastrointestinal tract with markedly higher level in the
      colon/rectum. These results indicate that the chicken neurotensin receptor 1 is
      involved in gastrointestinal functions through an intracellular signaling pathway
      accompanied by an increase in Ca(2+) levels.

PMID- 21199658
TI  - Exogenous cortisol facilitates responses to social threat under high provocation.
AB  - Stress is one of the most important promoters of aggression. Human and animal
      studies have found associations between basal and acute levels of the stress
      hormone cortisol and (abnormal) aggression. Irrespective of the direction of
      these changes--i.e., increased or decreased aggressive behavior--the results of
      these studies suggest dramatic alterations in the processing of threat-related
      social information. Therefore, the effects of cortisol and provocation on social
      information processing were addressed by the present study. After a placebo
      controlled pharmacological manipulation of acute cortisol levels, we exposed
      healthy individuals to high or low levels of provocation in a competitive
      aggression paradigm. Influences of cortisol and provocation on emotional face
      processing were then investigated with reaction times and event-related
      potentials (ERPs) in an emotional Stroop task. In line with previous results,
      enhanced early and later positive, posterior ERP components indicated a
      provocation-induced enhanced relevance for all kinds of social information.
      Cortisol, however, reduced an early frontocentral bias for angry faces and-
      despite the provocation-enhancing relevance--led to faster reactions for all
      facial expressions in highly provoked participants. The results thus support the
      moderating role of social information processing in the 'vicious circle of stress
      and aggression'.

PMID- 21199659
TI  - Active immunization with proteolipid protein (190-209) induces ascending
      paralysing experimental autoimmune encephalomyelitis in C3H/HeJ mice.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease of the
      central nervous system (CNS) that shares clinical and pathophysiological feature
      with multiple sclerosis (MS) and is commonly used as an animal model for the
      human disease. Upon active immunization, different myelin proteins and other
      neuronal antigens are known to induce EAE in susceptible mouse strains. However,
      there are rodent strains reputed to be resistant to actively-induced EAE and the
      correct combination of animal strains and their respective autoantigen is
      absolutely critical as some antigens are encephalitogenic in one animal strain,
      but not in another. Here we describe actively-induced EAE in C3H/HeJ mice with
      different myelin peptides. Whereas no clinical signs could be found by
      immunization with myelin oligodendrocyte glycoprotein 35-55, significant weight
      loss as well as rapidly occurring severe ascending paralysis was found in animals
      immunized with proteolipid protein 190-209 (PLP(190-209)). Histologically, this
      form of EAE was characterized by predominant involvement of the spinal cord. As
      PLP is one of the major lipid antigens putatively involved in the pathogenesis of
      MS, this model may be useful for further studies of the disease.

PMID- 21199660
TI  - Strain driven transport for bone modeling at the periosteal surface.
AB  - Bone modeling and remodeling has been the subject of extensive experimental
      studies. There have been several mathematical models proposed to explain the
      observed behavior, as well. A different approach is taken here in which the bone
      is treated from a macroscopic view point. In this investigation, a one
      dimensional analytical model is used to shed light on the factors which play the
      greatest role in modeling or growth of cortical bone at the periosteal surface.
      It is presumed that bone growth is promoted when increased amounts of bone
      nutrients, such as nitric oxide synthase (NOS) or messenger molecules, such as
      prostaglandin E2 (PGE2), seep out to the periosteal surface of cortical bone and
      are absorbed by osteoblasts. The transport of the bone nutrients is assumed to be
      a strain controlled process. Equations for the flux of these nutrients are
      written for a one-dimensional model of a long bone. The obtained partial
      differential equation is linearized and solved analytically. Based upon the
      seepage of nutrients out of the bone, the effect of loading frequency, number of
      cycles and strain level is examined for several experiments that were found in
      the literature. It is seen that bone nutrient seepage is greatest on the tensile
      side of the bone; this location coincides with the greatest amount of bone
      modeling.

PMID- 21199661
TI  - Transport effects on surface reaction arrays: biosensor applications.
AB  - The ubiquity of surface-volume reactions in biological and industrial processes
      makes knowledge of their kinetics critical. This has spurred technological
      advances in several biosensors designed to measure rate constants, such as the
      Flexchip and the dotLab. These biosensors have multiple reacting zones in a
      single flow channel, and hence they also serve as good model systems for
      biochemical systems with multiple reacting zones, such as cell membranes. A
      correct mathematical model for such systems must incorporate the effects of
      transport and zone position. A basic unidirectional flow model is developed in
      general and solved for typical experimental parameters using perturbation
      methods. The effect of zone placement along the channel can be quantified in
      terms of an effective Damkohler number based upon position. Moreover, it is
      established that zone placement across the channel does not affect the
      measurements.

PMID- 21199662
TI  - A supramodal representation of the body surface.
AB  - The ability to accurately localize both tactile and painful sensations on the
      body is one of the most important functions of the somatosensory system. Most
      accounts of localization refer to the systematic spatial relation between skin
      receptors and cortical neurons. The topographic organization of somatosensory
      neurons in the brain provides a map of the sensory surface. However, systematic
      distortions in perceptual localization tasks suggest that localizing a
      somatosensory stimulus involves more than simply identifying specific active
      neural populations within a somatotopic map. Thus, perceptual localization may
      depend on both afferent inputs and other unknown factors. In four experiments, we
      investigated whether localization biases vary according to the specific skin
      regions and subset of afferent fibers stimulated. We represented localization
      errors as a 'perceptual map' of skin locations. We compared the perceptual maps
      of stimuli that activate Abeta (innocuous touch), Adelta (pinprick pain), and C
      fibers (non-painful heat) on both the hairy and glabrous skin of the left hand.
      Perceptual maps exhibited systematic distortions that strongly depended on the
      skin region stimulated. We found systematic distal and radial (i.e., towards the
      thumb) biases in localization of touch, pain, and heat on the hand dorsum. A less
      consistent proximal bias was found on the palm. These distortions were
      independent of the population of afferent fibers stimulated, and also independent
      of the response modality used to report localization. We argue that these biases
      are likely to have a central origin, and result from a supramodal representation
      of the body surface.

PMID- 21199663
TI  - Traits of the metabolic syndrome alter corpulent obesity in LAN, SHR and DSS
      rats: behavioral and metabolic interactions with adrenalectomy.
AB  - Obesity results from a complex interaction of genes with environmental factors.
      Our experimental design compared obesity in three rat strains with the corpulent
      (cp) mutation. The three strains included Lister and Albany NIH (LAN) rats,
      Spontaneously Hypertensive Rats (SHR) and Dahl Salt Sensitive (DSS) rats that
      were congenically bred. The strains were selected because of different reported
      metabolic complications generally clustered with obesity, and defined as the
      metabolic syndrome. Body weight, food intake, carcass composition, plasma
      hormones and hypothalamic expression of Y5 receptors were assessed in obese (cp)
      and lean (wt) rats after adrenalectomy (ADX) or sham surgeries. Plasma
      corticosterone in sham-operated wtDSS and cpDSS were significantly higher
      (approx. 165ng/ml) than that in cpLAN and cpSHR (~77 and 68ng/ml respectively).
      All cp groups had a higher % carcass fat than wt groups. The % carcass fat was
      greater in cpDSS>cpLAN>cpSHR but plasma leptin was greatest in cpLAN>cpSHR>cpDSS.
      Hypothalamic expression of the Y5R after ADX resulted in a phenotype*surgery
      interaction since Y5R expression was slightly increased in cp rats and slightly
      decreased in wt rats. The strain with greatest number of metabolic syndrome
      traits, SHR, was not the fattest of the strains and had little response to ADX.
      The strains with fewer metabolic syndrome traits LAN and DSS had more extreme
      obesities which were attenuated after ADX. The results of the current experiment
      provide evidence that the corpulent mutation is not fully characterized in one
      strain.

PMID- 21199664
TI  - The possible role of penaeidin5 from the black tiger shrimp, Penaeus monodon, in
      protection against viral infection.
AB  - Penaeidin class 5 (PEN5) has so far only been reported in the Chinese shrimp,
      Fenneropenaeus chinensis, and the black tiger shrimp, Penaeus monodon. The PEN5
      homolog from F. chinensis (FenchiPEN5) exhibits antimicrobial activities against
      both Gram-positive and Gram-negative bacteria as well as fungi. Here, we
      characterized the PEN5 gene from P. monodon (PenmonPEN5) and evaluated its
      potential involvement in antiviral immunity. The deduced open reading frame of
      PenmonPEN5 encodes for a predicted 79 amino acid peptide including a 19 amino
      acid signal peptide. The gene structure of PenmonPEN5 contains two exons
      interrupted by one intron, whilst the 5' upstream sequence contains a putative
      TATA box and several GATA, GATA-3, AP-1 and dorsal transcription factor binding
      sites. PenmonPEN5 mRNA levels in P. monodon shrimps following a systemic
      infection with white spot syndrome virus (WSSV) were significantly induced at 24
      h post infection, but was strongly down-regulated at 48 h post injection,
      compared to those of the uninfected control shrimps. The suppression of
      PenmonPEN5 transcript levels by RNA interference mediated gene silencing led to
      an increased susceptibility of shrimps to WSSV infection, suggesting a possible
      role of PenmonPEN5 in the shrimp's antiviral immunity.

PMID- 21199665
TI  - Evaluation of a shortened QIAsymphony DNA extraction protocol for stool samples
      using a multiplex real-time PCR for the detection of enteric pathogens.
AB  - A shortened DNA extraction protocol for the QIAsymphony SP was evaluated by
      quantitative and qualitative comparison of real-time PCR results of 150 co
      extracted stool samples. The average ?Cycle threshold value for positive
      pathogenic targets was 0.28 Ct. A consensus of 96.91%, with a correlation
      coefficient of 0.9880 was recorded.

PMID- 21199666
TI  - Comparison of the QIAsymphony automated nucleic acid extraction and PCR setup
      platforms with NucliSens easyMAG and Corbett CAS-1200 liquid handling station for
      the detection of enteric pathogens in fecal samples.
AB  - In this study we compared the QIAsymphony Sample Preparation and Assay Setup
      modules (Qiagen), which provide automated nucleic acid extraction and PCR setup,
      to the NucliSens easyMAG (bioMerieux) and CAS-1200 liquid handling station
      (Corbett) for a molecular screening approach of enteric pathogens in fecal
      samples using multiplex real-time PCR. The relative DNA recovery of both
      platforms, within- and between-run reproducibility and a prospective study,
      including 510 clinical fecal samples, were performed. The results demonstrated
      that the QIAsymphony Sample Preparation and Assay Setup modules were highly
      reproducible and achieve equal performance, quantitative and qualitative, when
      compared with the NucliSens easyMAG and CAS-1200 systems for the molecular
      screening analysis of enteric pathogens in fecal samples.

PMID- 21199667
TI  - Curcumin enhances neuronal survival in N-methyl-d-aspartic acid toxicity by
      inducing RANTES expression in astrocytes via PI-3K and MAPK signaling pathways.
AB  - OBJECT: Neuroinflammation, which is characterized by the overproduction of
      cytokines and chemokines, plays an important role in neurodegenerative diseases,
      especially in Alzheimer's disease (AD). In the brain, chemokines are
      predominantly released by astrocytes and microglias. Expression of RANTES, as
      well as other cytokines, is involved in the inflammatory cascade that contributes
      to neurodegeneration in AD. Expression of RANTES may also have a neuroprotective
      effect. We sought to investigate whether curcumin exhibited neuroprotective and
      antioxidant activity via enhanced RANTES expression by astrocytes in cortical
      neuron cultures. We evaluated the neuroprotective and anti-neurodegenerative
      effects of curcumin in NMDA toxicity and in long-term cultures. METHODS: Pregnant
      female Sprague-Dawley (SD) rats were used for primary culture of cortical
      neurons, and neonatal 0- to 2-day-old SD rats were used for primary culture of
      astrocytes. Cultured astrocytes were conditioned with curcumin to prepare
      astrocyte-conditioned medium (ACM). Real-time polymerase chain reaction was
      performed to assess RANTES and iNOS mRNA expression in astrocytes following
      curcumin treatment. ELISA was used to detect astrocyte-secreted RANTES protein in
      ACM with curcumin treatment. JAK/STAT, PI-3K, PKC and MAPK inhibitors were used
      to ascertain whether the effects of curcumin involved these signaling pathways.
      To evaluate the effects of curcumin-enhanced astrocytes on neuronal survival,
      cultured cortical neurons treated or untreated with NMDA were incubated in ACM
      with or without curcumin treatment. Long-term culture (15days in vitro, DIV) was
      performed to investigate the effects of curcumin-treated astrocytes on the
      survival of cultured cortical neurons. Neuronal survival rate was assessed by
      using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      reduction activity assay (for cell viability), and the lactate dehydrogenase
      (LDH) release assay (for cell death). RESULTS: We demonstrated that curcumin
      enhanced RANTES expression in primary cultured astrocytes, and that this effect
      was related to activation of PI-3K and MAPK signaling pathways. We found that
      curcumin inhibited iNOS expression in primary cultured astrocytes in non-stressed
      condition. We also found that neurons exposed to NMDA and cultured with curcumin
      treated ACM, which characteristically exhibited elevated RANTES expression showed
      higher level of cell viability and lower level of cell death. Using a small
      interfering RNA (siRNA) knockdown model, we found evidence that the basal level
      of RANTES expression in non-stimulated astrocytes provided neuroprotection.
      CONCLUSION: We postulate that the enhanced neuronal survival by curcumin
      treatment in NMDA toxicity and long-term cultures was in part attributable to
      elevated astrocyte-derived RANTES expression via activation of PI3K/MAPK
      signaling pathways.

PMID- 21199668
TI  - Decreased galanin serum levels are associated with alcohol-craving during
      withdrawal.
AB  - BACKGROUND: The hypothalamic galanin expression has been associated with
      increased intake of carbohydrates and fats in preclinical studies. The appetite
      stimulating effect of galanin is thought to underlie the positive association
      between alcohol consumption and hypothalamic galanin expression observed in
      preclinical studies. METHODS: In this pilot study we investigated alterations in
      galanin serum levels (33 male patients) in alcohol-dependent patients during
      alcohol withdrawal (days 1, 7 and 14) in comparison to healthy controls (19 male
      controls). In order to assess the putative association between appetite
      regulation, galanin serum levels and alcohol consumption we additionally
      investigated the serum levels of insulin, glucose and triglycerides. RESULTS: The
      galanin serum levels on day 1 of alcohol withdrawal were significantly reduced in
      the alcohol-dependent patients (T=-3.302, p=0.002) and increased significantly
      from day 1 to day 14 of alcohol withdrawal (F=6.437, p=0.002). We found a
      significant negative association between the galanin serum levels and alcohol
      craving measured by the Obsessive Compulsive Drinking Scale (OCDS) (r=-0.449,
      p=0.009) and the obsessive subscale of the OCDS (r=-0.521, p=0.002) on day 1 of
      alcohol withdrawal. There was no association between the galanin serum levels and
      the parameters of energy homeostasis (triglycerides, cholesterol, insulin, and
      glucose) investigated. CONCLUSIONS: Acute alcohol withdrawal was associated with
      decreased galanin serum levels in this pilot study. There was no association
      between the galanin serum levels and the parameters of energy homeostasis.
      Further research of galanin serum levels in active drinkers will be necessary to
      clarify the putative association between galanin serum levels, appetite
      regulation and alcohol consumption.

PMID- 21199669
TI  - ER stress impairs MHC Class I surface expression and increases susceptibility of
      thyroid cells to NK-mediated cytotoxicity.
AB  - We recently reported that, in thyroid cells, ER stress triggered by thapsigargin
      or tunicamycin, two well known ER stressing agents, induced dedifferentiation and
      loss of the epithelial phenotype in rat thyroid cells. In this study, we sought
      to evaluate if, in thyroid cells, ER stress could affect MHC class I expression
      and the possible implications of this effect in the alteration of function of
      natural killer cells, suggesting a role in thyroid pathology. In both, a human
      line of fetal thyroid cells (TAD-2 cells) and primary cultures of human thyroid
      cells, thapsigargin and tunicamicin triggered ER stress evaluated by BiP mRNA
      levels and XBP-1 splicing. In both cell types, TAD-2 cell line and primary
      cultures, major histocompatibility complex class I (MHC-I) plasmamembrane
      expression was significantly reduced by ER stress. This effect was accompanied by
      signs of natural killer activation. Thus, natural killer cells dramatically
      increased IFN-gamma production and markedly increased their cytotoxicity against
      thyroid cells. Together, these data indicate that ER stress induces a decrease of
      MHC class I surface expression in thyroid cells, resulting in reduced natural
      killer-cell self-tolerance.

PMID- 21199670
TI  - Involvement of PI3K/Akt signaling in PTTH-stimulated ecdysteroidogenesis by
      prothoracic glands of the silkworm, Bombyx mori.
AB  - The prothoracicotropic hormone (PTTH) stimulates ecdysteroidogenesis by
      prothoracic gland in larval insects. Previous studies showed that Ca(2+), cAMP,
      extracellular signal-regulated kinase (ERK), and tyrosine kinase are involved in
      PTTH-stimulated ecdysteroidogenesis by the prothoracic glands of both Bombyx mori
      and Manduca sexta. In the present study, the involvement of phosphoinositide 3
      kinase (PI3K)/Akt signaling in PTTH-stimulated ecdysteroidogenesis by B. mori
      prothoracic glands was further investigated. The results showed that PTTH
      stimulated ecdysteroidogenesis was partially blocked by LY294002 and wortmannin,
      indicating that PI3K is involved in PTTH-stimulated ecdysteroidogenesis. Akt
      phosphorylation in the prothoracic glands appeared to be moderately stimulated by
      PTTH in vitro. PTTH-stimulated Akt phosphorylation was inhibited by LY294002. An
      in vivo PTTH injection into day 6 last instar larvae also increased Akt
      phosphorylation of the prothoracic glands. In addition, PTTH-stimulated ERK
      phosphorylation of the prothoracic glands was not inhibited by either LY294002 or
      wortmannin, indicating that PI3K is not involved in PTTH-stimulated ERK
      signaling. A23187 and thapsigargin, which stimulated B. mori prothoracic gland
      ERK phosphorylation and ecdysteroidogenesis, could not activate Akt
      phosphorylation. PTTH-stimulated ecdysteroidogenesis was not further activated by
      insulin, indicating the absence of an additive action of insulin and PTTH on the
      prothoracic glands. The present study, together with the previous demonstration
      that insulin stimulates B. mori ecdysteroidogenesis through PI3K/Akt signaling,
      suggests that crosstalk exists in B. mori prothoracic glands between insulin and
      PTTH signaling, which may play a critical role in precisely regulated
      ecdysteroidogenesis during development.

PMID- 21199671
TI  - Spontaneous acceptance of mouse kidney allografts is associated with increased
      Foxp3 expression and differences in the B and T cell compartments.
AB  - Spontaneous acceptance of organ allografts can identify novel mechanisms of drug
      free transplantation tolerance. Spontaneous acceptance occurs in both mouse
      kidney transplants and rat liver transplants however the early immune processes
      of mouse kidney acceptance have not been studied. Acceptance of C57BL/6 strain
      kidney allografts in fully MHC-incompatible B10.BR recipients was compared with
      rejection (REJ) of heart allografts in the same strain combination. Graft
      infiltrate and antibody deposition were examined by immunohistochemical staining.
      Expression of mRNA was measured by quantitative real-time PCR. Apoptosis was
      examined by TUNEL staining. The majority of kidney allografts were accepted long
      term and induced tolerance (TOL) of donor-strain skin grafts, showing that
      acceptance was not due to immune ignorance. There was an extensive infiltrate of
      T cells in the TOL kidney that exceeded the level in REJ hearts but subsequently
      declined. The main differences were deposition of IgG2a antibody in REJ that was
      absent in TOL, more B cells infiltrating TOL kidneys and a progressive increase
      in the ratio of CD8:CD4 cells during rejection. There was also significantly
      greater Foxp3 mRNA expression in TOL. Kidneys from RAG-/- donors were accepted,
      showing that donor lymphocytes were not necessary for acceptance. Neutralising
      antibodies to TGF-beta administered from day 0 to day 6 did not prevent TOL. On
      the basis of cytokine expression and apoptosis there was no evidence for immune
      deviation or deletion as mechanisms of acceptance. In accord with the findings of
      spontaneous acceptance of liver allografts in rats, the main difference between
      mouse kidney TOL and heart REJ was in the B cell compartment. The major
      difference to rat liver allograft acceptance was that apoptosis of infiltrate did
      not appear to play a role. Instead, increased Foxp3 expression in TOL kidneys
      implies that regulatory T cells might be important.

PMID- 21199672
TI  - Use of rapid cytochemical staining to characterize fish blood granulocytes in
      species of special concern and determine potential for function testing.
AB  - Studies of innate immunity in fish species of special concern are essential for
      better understanding of their health status during hatchery rearing conditions.
      The cytochemical and morphological characterizations of blood granulocytes have
      been used to provide information about phylogenetic differences and determine the
      potential use of neutrophil function assays. Rapid, simple, cytochemical staining
      kits used routinely for staining mammalian granulocytes have been used to
      characterize granulocytes from blood of four fish species: Arctic grayling,
      cutthroat trout, June sucker, and shovelnose sturgeon. Blood smears were stained
      with Peroxidase 391 (myeloperoxidase, MPO), alkaline phosphatase (AP), Periodic
      Acid Schiff (PAS) and Diff-quick stain; examined using bright field and
      differential interference contrast microscopy. Granulocytes on blood smears were
      evaluated based on the cell morphology, and presence or absence of the specific
      chromogen. Presence of lymphocytes, monocytes, platelets/thrombocytes and
      granulocytes was determined in all fish species. Arctic grayling, June sucker,
      and cutthroat trout had MPO positive granulocytes, while shovelnose sturgeon
      heterophils had positive reaction for leukocyte AP, but not MPO. Presence of MPO
      indicated potential to measure oxidative burst and degranulation of neutrophil
      primary granules in Arctic grayling, cutthroat trout and June sucker. Absence of
      MPO in shovelnose sturgeon suggested use of different enzyme marker (AP) in
      degranulation assay for this species. Standardization of cytochemical techniques
      allowed for rapid screening of leukocyte types, reducing the number of fish, time
      and effort to select adequate neutrophil function assays to be used in studies of
      health status in species of special concern.

PMID- 21199673
TI  - Identification of fatty acid synthase from the Pacific white shrimp, Litopenaeus
      vannamei and its specific expression profiles during white spot syndrome virus
      infection.
AB  - Fatty acid synthase (FAS) in animal tissues consists of two identical monomers
      and is known to be a complex multi-functional enzyme that plays an important role
      in energy homeostasis. However, there are few reports of studies focused on the
      relationship between FAS and virus infection in invertebrates. In the present
      study, we cloned the FAS gene from an economically important invertebrate, the
      Pacific white shrimp Litopenaeus vannamei. The full-length FAS cDNA is 8268 bp,
      including a 5'-terminal untranslated region of 137 bp, a 3'-terminal untranslated
      region of 601 bp and an open reading frame of 7530 bp. FAS cDNA encodes a
      polypeptide of 2509 amino acid residues that contains a typical beta-ketoacyl
      synthase (KS) domain at the N-terminus, next to a malonyl/acetyltransferase (MAT)
      domain, a dehydrase domain, an enoyl reductase domain, a ketoacyl reductase
      domain, a phosphopantetheine attachment site domain and a thioesterase domain at
      the C-terminus. Quantitative real-time RT-PCR revealed the up-regulated
      expression of FAS in L. vannamei hepatopancreas and muscle after white spot
      syndrome virus (WSSV) infection. The expression of FAS in muscle was 13.03-fold
      greater than that in the control (p<0.05) and 2.93-fold greater in hepatopancreas
      (p>0.05). Meanwhile, expression of the fatty acid-binding protein (FABP), another
      important factor in lipid metabolism, was increased in muscle to 19.20-fold
      greater than that in the control (p<0.05) but only 0.76-fold in hepatopancreas
      (p>0.05). These results implied that WSSV infected body surface tissues, but
      there was very little infection of internal organs. We suggest that the increase
      of FAS expression is induced in WSSV-infected shrimps, and the virus changes the
      lipid metabolism of the host, which directly affects virus assembly or defense
      against virus infection.

PMID- 21199674
TI  - The NO-responsive hemoglobins of Campylobacter jejuni: concerted responses of two
      globins to NO and evidence in vitro for globin regulation by the transcription
      factor NssR.
AB  - Campylobacter jejuni possesses NO-responsive and -detoxifying mechanisms to
      survive NO during transmission and pathogenesis. C. jejuni possesses two
      hemoglobins. The first (Cgb) is a single-domain (non-flavo)hemoglobin encoded by
      gene Cj1586 (cgb), mutation of which leads to hypersensitivity to S
      nitrosoglutathione and NO. Transcription of cgb is induced by nitrosative stress
      and confers resistance to NO, presumably via a Cgb-catalyzed dioxygenase or
      denitrosylase reaction that converts NO and oxygen to nitrate. Expression of Cgb
      in response to NO is mediated via the positively-acting transcription factor
      NssR, which regulates expression of a small regulon that includes cgb and ctb
      (Cj0465c), the latter encoding the truncated hemoglobin, Ctb. The role of Ctb is
      unclear: it is not directly involved in NO detoxification but is implicated in
      oxygen delivery or metabolism. Here, we describe attempts to define a function
      for Ctb by examining the effects of a ctb mutation on the NO transcriptome and
      cgb gene expression during normoxia and hypoxia. Mutation of ctb does not elicit
      major compensatory transcriptomic changes but relatively minor changes in genes
      involved in intermediary metabolism, solute transport and signal transduction. We
      present and test the hypothesis that, by binding NO or O(2), Ctb dampens the
      response to NO under hypoxic conditions and limits cgb expression, perhaps
      because Cgb function (i.e. NO detoxification) requires O(2)-dependent chemistry.
      We report the purification of NssR and specific binding to the ctb promoter. GSNO
      does not affect the high affinity of NssR for the ctb promoter.

PMID- 21199676
TI  - Protective effect of bicyclol on lipopolysaccharide-induced acute lung injury in
      mice.
AB  - Bicyclol is synthesized based on schisandrin, which is one of the main active
      components of Chinese herb Fructus Schisandrae. The purpose of this study is to
      investigate whether bicyclol has a beneficial effect on lipopolysaccharide (LPS)
      induced acute lung injury (ALI) in mice. Bicyclol was given to mice by gavage for
      three times. ALI was induced by vena caudalis injection of LPS. The last dose of
      bicyclol was administrated 1 h before LPS given. Mice in each group were
      sacrificed at different time point after LPS administration. As revealed by
      survival study, pretreatment with high doses of bicyclol reduced the mortality of
      mice from ALI. Bicyclol pretreatment significantly improved LPS-induced lung
      pathological changes, inhibited myeloperoxidase (MPO) activity, and reduced
      lung/body and lung wet/dry weight ratios. Bicyclol also inhibited the release of
      TNF-alpha, IL-1beta and HMGB1, whereas simultaneously increased the expression of
      IL-10. Furthermore, the phosphorylation level of NF-kappaB p65 was markedly
      decreased by bicyclol. Taken together, our study showed that bicyclol improves
      survival rate and attenuates LPS-induced ALI. The protective mechanism may be due
      to the inhibition of NF-kappaB activation and regulation of cytokine secretion.

PMID- 21199677
TI  - The transcription of l-gulono-gamma-lactone oxidase, a key enzyme for
      biosynthesis of ascorbate, during development of Persian sturgeon Acipenser
      persicus.
AB  - l-Gulono-gamma-lactone oxidase (GULO) is a key enzyme for the biosynthesis of
      ascorbate, which is essential for several cellular functions. In the present
      study, mRNA expression of GULO gene was evaluated during the early development of
      Persian sturgeon. First, because there are no comparative studies that have
      established suitable quantitative real-time PCR reference genes in sturgeons for
      any physiological conditions, we evaluated six candidate reference genes (ACTB,
      RPL13, UBQ, RPL6, GAPDH and EF1A) during the early development of Persian
      sturgeon. The most stable mRNA expression was obtained with RPL6 and ACTB,
      whereas the least stable was RPL13. After normalization using RPL6, ACTB and
      RPL6/ACTB combination, the mRNA expression of GULO was highest at the embryonic
      stage (2days before hatching; P<0.05) and started to decline from hatching of
      larvae to the rest of the developmental time-points. This suggests that the
      vitamin C requirements are highest during early life stages, and it is likely
      that the changes in GULO mRNA expression are associated with changes in GULO
      enzyme activity.

PMID- 21199678
TI  - Purification, molecular cloning, and some properties of a manganese-containing
      superoxide dismutase from Japanese flounder (Paralichthys olivaceus).
AB  - Manganese-superoxide dismutase (Mn-SOD) from Japanese flounder (Paralichthys
      olivaceus) hepatopancreas has been purified with high purification (781-fold) and
      recovery (10.8%). The molecular mass of the purified enzyme was estimated to be
      26kDa by SDS-PAGE under reducing conditions. In activity staining by native-PAGE,
      the Japanese flounder Mn-SOD gave three active bands and exhibited KCN
      insensitive activity. In addition, the electrophoretic mobility of this enzyme
      was observed to be faster than that of Japanese flounder Cu,Zn-SOD. On the other
      hand, the N-terminal amino acid sequence of this Mn-SOD was determined to be 16
      amino acid residues, and the sequence showed high homology to other Mn-SODs but
      not Japanese flounder Cu,Zn-SOD. Analysis of nucleotide and deduced amino acid
      sequences revealed that the Mn-SOD cDNA consisted of a 64bp 5'-non-coding region,
      a 675bp open reading frame encoding 225 amino acids, and a 465bp 3'-non-coding
      region. The first 27 amino acids containing a mitochondria-targeting signal were
      highly conserved among other Mn-SODs.

PMID- 21199675
TI  - Interactions between nitric oxide and hypoxia-inducible factor signaling pathways
      in inflammatory disease.
AB  - Induction and activation of nitric oxide (NO) synthases (NOS) and excessive
      production of NO are common features of almost all diseases associated with
      infection and acute or chronic inflammation, although the contribution of NO to
      the pathophysiology of these diseases is highly multifactorial and often still a
      matter of controversy. Because of its direct impact on tissue oxygenation and
      cellular oxygen (O(2)) consumption and re-distribution, the ability of NO to
      regulate various aspects of hypoxia-induced signaling has received widespread
      attention. Conditions of tissue hypoxia and the activation of hypoxia-inducible
      factors (HIF) have been implicated in hypoxia or in cancer biology, but are also
      being increasingly recognized as important features of acute and chronic
      inflammation. Thus, the activation of HIF transcription factors has been
      increasingly implicated in inflammatory diseases, and recent studies have
      indicated its critical importance in regulating phagocyte function, inflammatory
      mediator production, and regulation of epithelial integrity and repair processes.
      Finally, HIF also appears to contribute to important features of tissue fibrosis
      and epithelial-to-mesenchymal transition, processes that are associated with
      tissue remodeling in various non-malignant chronic inflammatory disorders. In
      this review, we briefly summarize the current state of knowledge with respect to
      the general mechanisms involved in HIF regulation and the impact of NO on HIF
      activation. Secondly, we will summarize the major recent findings demonstrating a
      role for HIF signaling in infection, inflammation, and tissue repair and
      remodeling, and will address the involvement of NO. The growing interest in
      hypoxia-induced signaling and its relation with NO biology is expected to lead to
      further insights into the complex roles of NO in acute or chronic inflammatory
      diseases and may point to the importance of HIF signaling as key feature of NO
      mediated events during these disorders.

PMID- 21199679
TI  - Hexokinase from the white shrimp Litopenaeus vannamei: cDNA sequence, structural
      protein model and regulation via HIF-1 in response to hypoxia.
AB  - Hexokinase (HK) catalyzes the phosphorylation of glucose, the first rate-limiting
      step in glycolysis. HKs are a conserved family of tissue-specific isozymes, from
      which very little is known in marine crustaceans. This study describes the
      cloning and characterization of the full-length cDNA sequence for HK from the
      shrimp Litopenaeus vannamei, the theoretical tridimensional protein structure and
      response to short-term hypoxia. The full-length cDNA is 1872bp long with an open
      reading frame of 1452bp coding for a protein of 484 amino acids and predicted
      molecular mass of 53kDa. Highly conserved amino acid residues are present in the
      glucose, glucose-6-phosphate, ATP and Mg(+2) binding sites. Phylogenetic analysis
      shows that the shrimp HK is closer to invertebrates than to vertebrate HKs.
      Hypoxia induced HK expression in gills with the concomitant increase in the
      specific enzyme activity. In muscle, hypoxia decreased HK mRNAs but increased the
      enzyme activity. Silencing of the hypoxia inducible factor 1 (HIF-1) affected the
      expression of HK differentially. In gills, silencing of alpha or beta subunits
      blocked the induction of HK expression and the enzymatic activity, but not in
      muscle. This suggests the existence of tissue-specific HK isozymes and post
      transcriptional and post-translational regulation of HK.

PMID- 21199680
TI  - Endothelial nitric oxide synthase in the amphibian, Xenopus tropicalis.
AB  - Nitric oxide (NO) is generated by NO synthase (NOS) of which there are three
      isoforms: neuronal NOS (nNOS, nos1), inducible NOS (iNOS, nos2), and endothelial
      NOS (eNOS, nos3). This study utilised the genome of Xenopus tropicalis to
      sequence a nos3 cDNA and determine if eNOS protein is expressed in blood vessels.
      A nos3 cDNA was sequenced that encoded a 1177 amino acid protein called XteNOS,
      which showed closest sequence identity to mammalian eNOS protein. The X.
      tropicalis nos3 gene and eNOS protein were determined to be an orthologue of
      mammalian nos3 and eNOS using gene synteny and phylogenetic analyses,
      respectively. In X. tropicalis, nos3 mRNA expression was highest in lung and
      skeletal muscle and lower in the liver, gut, kidney, heart and brain. Western
      analysis of kidney protein using an affinity-purified anti-XteNOS produced a
      single band at 140kDa. Immunohistochemistry showed XteNOS immunoreactivity in the
      proximal tubule of the kidney and endocardium of the heart, but not in the
      endothelium of blood vessels. Thus, X. tropicalis has a nos3 gene that appears
      not to be expressed in the vascular endothelium.

PMID- 21199681
TI  - L-ascorbic acid producing yeasts learn from plants how to recycle it.
AB  - Microorganisms employed in industrial fermentation processes are often subjected
      to a variety of stresses that negatively affect growth, production and
      productivity. Therefore, stress robustness is an important property for their
      application. Reactive Oxygen Species (ROS) accumulation is a common denominator
      to a lot of these stress factors. Ascorbic acid (L-AA) acts as ROS scavenger,
      thus potentially protecting cells from harmful oxidative products. We have
      previously reported the development of Saccharomyces cerevisiae strains able to
      produce L-AA. This was obtained by expressing the known plant pathway genes and
      by complementing the missing step with an animal activity. Here, we show that L
      AA accumulation inside yeast cells can be improved by expressing the complete
      biosynthetic plant pathway and, even further, by recycling its oxidation
      products. These new strains can be seen in a double perspective of exploitation:
      as novel organisms for vitamin C production and as novel cell factories for
      industrial processes.

PMID- 21199682
TI  - The mechanism for regulating ethanol fermentation by redox levels in
      Thermoanaerobacter ethanolicus.
AB  - Anaerobes can obtain the entire cell's ATP by glycolysis and remove resulting
      reducing power by fermentation. There is a delicate balance in redox status to
      obtain a maximal growth of these cells, and the conditions to change redox fluxes
      can induce kinds of changes in metabolism. The fundamental knowledge on sensing
      redox status and coupling redox signals with fermentation pathways is essential
      for the metabolic engineering to control redox fluxes at the molecular level. A
      redox sensing protein (RSP) was isolated by DNA affinity chromatography, and
      corresponding gene was mined from genomic sequences of Thermoanaerobacter spp.
      The RSP shares up to 41% identity with the regulatory proteins which sense NADH
      and control the expression of NADH dehydrogenase in aerobic microorganisms. The
      operator sites for RSP were located in all the operons for ethanol fermentation
      rather than in that of NADH dehydrogenase. The typical operator was identified as
      a palindromic sequence, -ATTGTTANNNNNNTAACAAT-. NADH caused a transition of RSP
      from an alpha-helix rich to beta-sheet rich conformation. In an in vitro
      transcription system of T. ethanolicus, RSP repressed the transcription of an
      alcohol dehydrogenase, whereas the repression was reversed by adding NADH. Base
      substitutes in the repeats of the palindrome reduced the affinity between RSP and
      the operator, and thus delicate regulation could be achieved. This study reveals
      for the first time a repressor/operator system that couples a redox signal with a
      fermentation pathway, and the results presented here provide valuable insights
      for the design of metabolic engineering.

PMID- 21199683
TI  - Different p97/VCP complexes function in retrotranslocation step of mammalian ER
      associated degradation (ERAD).
AB  - Studies in yeast indicate that three specialized endoplasmic reticulum-associated
      degradation (ERAD) pathways, namely ERAD-L, -M, or -C, dispose substrates with
      structural lesions in the lumenal, transmembrane, or cytosolic domains,
      respectively. The ubiquitin ligase (E3) Hrd1p and its cooperating partners are
      required for ERAD-L and -M pathways, whereas Doa10p complex is required for the
      ERAD-C pathway. We investigated these pathways in mammalian cells by assessing
      the requirements of the mammalian ERAD E3s, gp78 and Hrd1, in degradation of four
      substrates each with different type of structural lesions: CD3delta, Z-variant
      alpha1-antitrypsin, tyrosinase (C89R) and mutant cystic fibrosis transmembrane
      conductance regulator (CFTRDeltaF508). We demonstrated that tyrosinase (C89R) is
      a substrate for Hrd1 while all others are gp78 substrates. Knockdown of Hrd1
      diminished gp78 substrate levels, but silencing of gp78 had no effect on Hrd1's
      substrate, suggesting that the functional interaction between Hrd1 and gp78 is
      unidirectional. Furthermore, while Ufd1 is dispensable for gp78-mediated ERAD, it
      is essential for Hrd1-mediated ERAD. Interestingly, Npl4 was found to be a key
      component for both pathways. These results suggest that the Hrd1-mediated ERAD
      requires a well-established retrotranslocation machinery, the p97/VCP-Ufd1-Npl4
      complex, whereas the gp78 pathway needs only p97/VCP and Npl4. In addition, the
      three distinct ERAD pathways described in yeast may not be strictly conserved in
      mammalian cells as gp78 can function on three substrates with different
      structural lesions.

PMID- 21199684
TI  - Purification and properties of antimicrobial peptides from skin secretions of the
      Eritrea clawed frog Xenopus clivii (Pipidae).
AB  - Five peptides with antimicrobial activity were isolated from norepinephrine
      stimulated skin secretions of the tetraploid frog Xenopus clivii Peracca, 1898
      (Pipidae). Characterization of the peptides demonstrated that they are
      structurally similar to magainins (2 peptides), caerulein-precursor fragments,
      CPF (2 peptides), and xenopsin-precursor fragments, XPF (1 peptide) that have
      been previously isolated from other species of the genus Xenopus. The magainins
      and the XPF peptide were active only against the Gram-negative microorganism
      Escherichia coli whereas the CPF peptides were also active against the Gram
      positive Staphylococcus aureus. The most abundant antimicrobial peptide in the
      secretions, CPF-C1 (GFGSLLGKALRLG ANVL.NH(2)) inhibited the growth of the Gram
      negative bacteria Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas
      aeruginosa (MIC<=25MUM) suggesting potential for development into an anti
      infective agent for use against these emerging antibiotic-resistant pathogens.

PMID- 21199685
TI  - ECG screening for athletes: letting evidence and reason advance the debate.

PMID- 21199686
TI  - Rapid pulmonary vein isolation combined with autonomic ganglia modification: a
      randomized study.
AB  - BACKGROUND: Evidence indicates that the combination of left atrial ganglionated
      plexi (GP) ablation and pulmonary vein (PV) isolation is beneficial for treatment
      of paroxysmal atrial fibrillation (AF). OBJECTIVE: The purpose of this study was
      to compare GP and PV ablation with PV isolation alone for treatment of paroxysmal
      AF. METHODS: Sixty-seven patients with paroxysmal AF were randomized to either PV
      isolation using a circular catheter suitable for both mapping and ablation (PV
      group) or anatomic GP modification followed by PV isolation (GP+PV group).
      Patients were seen at monthly visits, and 48-hour ambulatory ECG recordings were
      obtained every 3 months for a predefined follow-up period of 12 months. Primary
      endpoint was freedom from AF or other sustained atrial arrhythmia recurrence 3 to
      12 months postablation after one or two procedures, without antiarrhythmic
      medications. RESULTS: Recurrence of arrhythmia was documented in 18 (54.5%)
      patients in the PV group 4.7 +/- 1.0 months after ablation, and repeat PV
      isolation was performed in 7 (21.2%) of these patients 5.1 +/- 1.1 months after
      the first procedure. Recurrence of arrhythmia was documented in 9 (26.5%)
      patients in the GP+PV group 5.0 +/- 1.3 months after ablation, and repeat
      ablation was performed in 6 (17.6%) of these patients 4.3 +/- 0.5 months after
      the first procedure. At the end of follow-up, 20 (60.6%) patients in the PV group
      and 29 (85.3%) patients in the GP+PV group remained arrhythmia-free (log rank
      test, P = .019). CONCLUSION: Addition of anatomic GP modification to PV isolation
      confers significantly better outcomes than PV isolation alone during a follow-up
      period of 12 months.

PMID- 21199687
TI  - Does omega-3 fatty acid supplementation prevent atrial fibrillation, and if so,
      which type?

PMID- 21199688
TI  - Unexpected pacing inhibition upon exposure to the 3T static magnetic field prior
      to imaging acquisition: what is the mechanism?

PMID- 21199689
TI  - Bayesian sample size determination under hypothesis tests.
AB  - We develop a Bayesian approach for calculating sample sizes for clinical trials
      under the framework of hypothesis tests. We extend the work of Weiss (The
      Statistician 1997; 46: 185-191) to include composite distributions for the
      treatment effect and the variance of the data within the null and alternative
      hypotheses. We select sample sizes using the Bayes factor and the averaged type I
      error and type II error defined by Weiss (The Statistician 1997; 46: 185-191).
      Our approach allows the uncertainty inherent in eliciting prior information for
      both the treatment effect and the variance and permits informative prior
      information for unknown quantities through the hypothesis specification. We
      illustrate our method through a real data example from a clinical trial for
      treatment of multiple sclerosis and from the cerclage trial for preterm birth
      prevention in high-risk women.

PMID- 21199690
TI  - The impact of micro-embolism size on haemodynamic changes in the pulmonary micro
      circulation.
AB  - Embolus occlusion of pulmonary arteries can result in elevated pulmonary blood
      pressures, often resulting in pulmonary hypertension (PH). Experimental
      observations have shown that small emboli (diameter <170 MUm) can have a
      disproportionate effect on pulmonary vascular resistance (PVR) compared with
      larger emboli for the same tissue occlusion. We present an anatomically based
      theoretical model of perfusion in the acinar blood vessels designed to
      investigate changes in PVR following occlusion of arteries <500 MUm in diameter.
      The model predicts that emboli lodged near proximal capillary beds have a greater
      effect on PVR--regardless of their size--than emboli occluding 200 MUm diameter
      arterioles, with PH occurring for 10% less tissue occlusion. Capillary blood
      pressures are predicted to exceed 24 mmHg (levels initiating capillary wall
      damage) in regions of the capillary bed at approximately the onset of PH. This
      study focuses on the effect of mechanical obstruction alone; however, we present
      simple models of vasoconstriction illustrating an increased impact on PVR.

PMID- 21199691
TI  - Impact of the vagal feedback on cardiorespiratory coupling in anesthetized rats.
AB  - Cardiorespiratory coupling can be significantly influenced by both pontine and
      vagal modulation of medullary motor and premotor areas. We investigated
      influences of the pontine intertrigeminal region (ITR) and peripheral vagal
      pathways on the coupling between systolic blood pressure (SBP) and respiration in
      9 anesthetized rats. Glutamate injection into the ITR perturbed both respiration
      and SBP and decreased SBP-respiratory coherence (0.95+/-0.01 vs 0.89+/-0.02;
      (p=0.01). Intravenous infusion of serotonin (5-HT) produced apnea and
      hypertension and also decreased SBP-respiratory coherence (0.95+/-0.01 vs 0.72+/
      0.06; p=0.04). Bilateral vagotomy eliminated the cardiorespiratory coherence
      perturbations induced by central (glutamate injection into the ITR: 0.89+/-0.03
      vs 0.86+/-0.03; p=0.63) and peripheral (5-HT infusion: 0.89+/-0.03 vs 0.88+/
      0.02; p=0.98) pharmacologic manipulations. Glutamate stimulation of the ITR
      postvagotomy increased the relative spectral power density of SBP in the
      respiratory frequency range (0.25+/-0.08 vs 0.55+/-0.06; p=0.01). The data
      suggest that SBP-respiratory coupling is largely mediated within the central
      nervous system, with vagal systems acting in a way that disrupts coherence during
      transient cardiorespiratory disturbances. Although decreased cardiorespiratory
      coherence may increase cardiac work during perturbations, this may be
      physiologically advantageous in restoring homeostatic equilibrium of respiration
      and blood pressure.

PMID- 21199692
TI  - Analysis of the roles of microporosity and BMP-2 on multiple measures of bone
      regeneration and healing in calcium phosphate scaffolds.
AB  - Osteoinductive agents, such as BMP-2, are known to improve bone formation when
      combined with scaffolds. Microporosity (<20 MUm) has also been shown to influence
      bone regeneration in calcium phosphate (CaP) scaffolds. However, many studies use
      only the term "osteoconductive" to describe the effects of BMP-2 and
      microporosity on bone formation, and do not assess the degree of healing that
      occurred. The objective of this study was to quantify the influence of BMP-2 and
      microporosity on bone regeneration and healing in biphasic calcium phosphate
      scaffolds using multiple measures including bone volume fraction, radial
      distribution, and specific surface area. These measures were quantitatively
      compared by analyzing microcomputed tomography data and used to formally define
      and assess healing. A custom image segmentation program was used to segment >100
      samples, with 900 images each, that were implanted in porcine mandibular defects
      for 3, 6, 12 and 24 weeks. The assessment of healing presented in this work
      demonstrates the level of detail possible in evaluating scaffold-guided bone
      regeneration. The analysis shows that BMP-2 and microporosity accelerate healing
      up to 4-fold. BMP-2 and microporosity were shown to have different and
      complementary roles in bone formation that effect the time needed for a defect to
      heal.

PMID- 21199693
TI  - Behaviour of mesenchymal stem cells, fibroblasts and osteoblasts on smooth
      surfaces.
AB  - Understanding of the interactions between cells and surfaces is essential in the
      field of tissue engineering and biomaterials. This study aimed to compare the
      adhesion, proliferation and differentiation of human mesenchymal stem cells
      (hMSCs), an osteoblast cell line (MC3T3-E1) and gingival fibroblasts (HGF-1) on
      tissue culture polystyrene (TCPS), glass and titanium (Ti). The average surface
      roughness was 5, 0.2 and 40*10(-3) MUm for TCPS, glass and Ti, respectively.
      Immunocytochemistry and image analysis made it possible to quantify the number
      and morphology of adherent cells as well as the density of the focal points.
      Regardless of the substrate, both hMSCs and osteoblastic cells were mainly branch
      shaped. HGF-1 exhibited a significantly higher number of focal points on Ti than
      on TCPS and glass. Alizarin red quantification indicated that both hMSCs and
      osteoblastic cells were more differentiated on TCPS than on Ti and glass. The
      surface properties of substrates, such as roughness, wettability and chemical
      composition, modulated the behaviour of the cells. Early events, such as cell
      adhesion, may influence the differentiation of hMSC and consequently tissue
      healing around implanted biomaterials.

PMID- 21199694
TI  - Open gastrostomy by mini-laparotomy: a comparative study.
AB  - BACKGROUND: Gastrostomy tube feeding is the best option for long lasting
      nutritional support in patients with dysphagia caused by obstructive tumours of
      the mouth, pharynx, larynx and ooesophagus or neuromuscular diseases. However,
      these severely compromised patients often present severe respiratory risks,
      precluding the use of general anesthesia, sedation or even endoscopy. A
      simplified open gastrostomy (SOG) under local anesthesia has been in practice in
      our institution, especially for patients with severe neuromuscular diseases and
      continuous non-invasive ventilatory support. In this study, we try to compare the
      surgical outcomes of this technique, with the classical Stamm gastrostomy (SG).
      MATERIAL AND METHODS: This simplified technique uses a minimal vertical midline
      incision (3 cm), just below the xyphoid process, under local anesthesia. The
      gastrostomy tube is passed by a left lateral stab wound, inserted in a double
      purse-string in the gastric wall and pulled to the anterior abdominal wall. No
      sutures between the stomach and the peritoneum are placed. We retrospectively
      analyzed the clinical records of 63 consecutive gastrostomies performed upon a 3
      year period, 23 of which were by SOG. RESULTS: The SG was performed mainly in
      oncological patients, and SOG in patients with neuromuscular diseases (p <
      0.001). In the SOG group, 95,4% (n = 22) of the patients were ASA IV, compared
      with 74,4% (n = 29) in SG (p = 0,03). The mean operative time was shorter in the
      simplified technique (37 vs 60 min; p = 0,01). All the surgeries in the SOG group
      were performed exclusively with local anesthesia and in the Stamm procedure,
      47,5% required invasive ventilatory support (p < 0.001). There were no
      significant differences regarding in-hospital morbi-mortality (p = 0,18). The
      patients were able to receive adequate nutritional support, and the overall
      satisfaction of the patients and family/caregivers is very good. CONCLUSION: The
      simplified mini-laparotomy gastrostomy is a safe and effective alternative to
      other approaches. The association of local anesthesia with a minimal surgical
      offense and a short operative time render its effectiveness, even in high-risk
      patients.

PMID- 21199695
TI  - The face of Ulnar Mammary syndrome?
AB  - Ulnar Mammary syndrome (UMS) is an autosomal disorder caused by
      haploinsufficiency of the TBX3 gene. There is marked intrafamilial variation in
      expression of the syndrome. We present one three generation family in which the
      proband has absence of the right ulna and third, fourth and fifth rays in her
      right hand. Her mother and maternal grandmother have more subtle anomalies while
      all have a similar facial appearance with a broad nasal tip, a broad jaw, a
      prominent chin and a tongue frenulum. They have a single base pair insertion (c.
      992dup) in TBX3. We compare faces from the handful of published UMS patients
      which include photographs, this family and four other cases with TBX3 mutations.
      All have similarities in appearance which we suggest could alert clinicians to
      the possibility of a TBX3 mutation if individuals present with more subtle
      features of UMS such as postaxial polydactyly, isolated 5th finger anomalies,
      delayed puberty in males, breast hypoplasia or short stature with or without
      growth hormone deficiency.

PMID- 21199696
TI  - Determinants of bone size and strength in 13-year-old South African children: the
      influence of ethnicity, sex and pubertal maturation.
AB  - We have previously shown ethnic differences in bone mass between pre-pubertal
      black and white children using DXA. To investigate these ethnic differences
      further, using pQCT, and to determine the influence of sex and pubertal
      development, we measured appendicular bone variables in 13-year-old children
      using pQCT. We collected pQCT data on a cohort of 471 black and white children at
      age 13years. Black boys and girls were shorter and had less lean mass than their
      white peers, and black boys were lighter than white boys at an earlier stage of
      pubertal development. Metaphyseal (4%) radial trabecular density was greater in
      the black girls than their white peers (239.5+/-49.5 vs. 222.7+/-34.2 mg/cm(3);
      p<0.05). Bone strength index was not different between the ethnic groups. All
      metaphyseal measures were 3-41% greater in boys than girls, after adjusting for
      height where appropriate. Diaphyseal (38%) tibial values, including total area,
      endosteal diameter, tibial diameter, periosteal circumference and polar strength
      strain index were 4-22% greater in the black than white children and in boys than
      in girls. Cortical density was greater in black than white boys (1079.0+/-39.4
      vs. 1058.7+/-34.5 mg/mm(3); p<0.001) and greater in the girls than boys (black:
      1129.3+/-33.7 vs. 1079.0+/-39.4 mg/mm(3); p<0.001; white: 1126.8+/-28.3 vs.
      1058.7+/-34.5mg/mm(3); p<0.001). Cortical thickness was less in the black groups.
      Lower leg muscle cross-sectional area (MCSA) was higher in white than black
      children, and forearm MCSA was higher in white than black boys. There was no
      difference in fat cross-sectional area between the ethnic groups. In conclusion,
      ethnic and sex differences in both metaphyseal and diaphyseal bone parameters
      exist during puberty, which are not accounted for by differences in body size or
      skeletal maturity. South African black children have wider diaphyseal regions of
      appendicular bones with greater measures of bone strength.

PMID- 21199697
TI  - Involvement of CD8+ T cell-mediated immune responses in LcrV DNA vaccine induced
      protection against lethal Yersinia pestis challenge.
AB  - Yersinia pestis (Y. pestis) is the causative pathogen of plague, a highly fatal
      disease for which an effective vaccine, especially against mucosal transmission,
      is still not available. Like many bacterial infections, antigen-specific antibody
      responses have been traditionally considered critical, if not solely responsible,
      for vaccine-induced protection against Y. pestis. Studies in recent years have
      suggested the importance of T cell immune responses against Y. pestis infection
      but information is still limited about the details of Y. pestis antigen-specific
      T cell immune responses. In current report, studies are conducted to identify the
      presence of CD8+ T cell epitopes in LcrV protein, the leading antigen of plague
      vaccine development. Furthermore, depletion of CD8+ T cells in LcrV DNA
      vaccinated Balb/C mice led to reduced protection against lethal intranasal
      challenge of Y. pestis. These findings establish that an LcrV DNA vaccine is able
      to elicit CD8+ T cell immune responses against specific epitopes of this key
      plague antigen and that a CD8+ T cell immune response is involved in LcrV DNA
      vaccine-elicited protection. Future studies in plague vaccine development will
      need to examine if the presence of detectable T cell immune responses, in
      particular CD8+ T-cell immune responses, will enhance the protection against Y.
      pestis in higher animal species or humans.

PMID- 21199698
TI  - The development of vaccine viruses against pandemic A(H1N1) influenza.
AB  - Wild type human influenza viruses do not usually grow well in embryonated hens'
      eggs, the substrate of choice for the production of inactivated influenza
      vaccine, and vaccine viruses need to be developed specifically for this purpose.
      In the event of a pandemic of influenza, vaccine viruses need to be created with
      utmost speed. At the onset of the current A(H1N1) pandemic in April 2009, a
      network of laboratories began a race against time to develop suitable candidate
      vaccine viruses. Two approaches were followed, the classical reassortment
      approach and the more recent reverse genetics approach. This report describes the
      development and the characteristics of current pandemic H1N1 candidate vaccine
      viruses.

PMID- 21199699
TI  - Pandemic influenza A/H1N1 vaccine administered sequentially or simultaneously
      with seasonal influenza vaccine to HIV-infected children and adolescents.
AB  - In order to evaluate the immunogenicity, safety and tolerability of the 2009
      A/H1N1 MF59-adjuvanted influenza vaccine administered sequentially or
      simultaneously with seasonal virosomal-adjuvanted influenza vaccine to HIV
      infected children and adolescents, 36 HIV-infected children and adolescents, and
      36 age- and gender-matched healthy controls were randomised 1:1 to receive the
      pandemic vaccine upon enrollment and the seasonal vaccine one month later, or to
      receive the pandemic and seasonal vaccines simultaneously upon enrollment.
      Seroconversion and seroprotection rates against the pandemic influenza A/H1N1
      virus were 100% two months after vaccine administration in both groups,
      regardless of the sequence of administration. Geometric mean titres against
      pandemic and seasonal antigens were significantly higher when the seasonal and
      pandemic vaccines were administered simultaneously than when the seasonal vaccine
      was administered alone. Local and systemic reactions were mild and not increased
      by simultaneous administration. In conclusion, the 2009 pandemic influenza A/H1N1
      MF59-adjuvanted vaccine is as immunogenic, safe and well tolerated in HIV
      infected children and adolescents as in healthy controls. Its simultaneous
      administration with virosomal-adjuvanted seasonal antigens seems to increase
      immune response to both pandemic and seasonal viruses with the same safety
      profile as that of the pandemic vaccine alone. However, because this finding
      cannot be clearly explained by an immunological viewpoint, further studies are
      needed to clarify the reasons of its occurrence.

PMID- 21199700
TI  - Vaccination against the 2009 pandemic influenza A (H1N1) among healthcare workers
      in the major teaching hospital of Sicily (Italy).
AB  - The aim of the study was to investigate factors involved in vaccination
      acceptance among healthcare workers (HCWs) and adverse reactions rates associated
      with pandemic influenza vaccination. The study was carried out in the major
      teaching hospital of Sicily from November 2009 to February 2010 on 2267 HCWs. A
      total of 407 (18%) HCWs were vaccinated against the 2009 pandemic influenza A
      (H1N1). A logistic regression analysis indicates an increased risk of non
      vaccination against pandemic influenza in females (OR=1.6; 95% CI=1.3-2.1)
      compared to males, in nurses/technicians/administrative workers (OR=1.7; 95%
      CI=1.3-2.2) compared to doctors/biologists, and in HCWs who were non-vaccinated
      against seasonal influenza in 2008-2009 (OR=4.9; 95% CI=3.7-6.5) compared to
      vaccinated HCWs. Overall, 302 (74.2%) out of 407 questionnaires distributed to
      vaccinated HCWs were returned within the observation period. One hundred fifty
      two workers (50.3%) experienced at least one adverse reaction (30.1%, local
      reactions; 6.6% systemic reactions and 13.6% both of them). The most frequent
      side effect of vaccination was pain at the injection site (43.4%). Twelve (3.9%)
      out of 302 HCWs stated they experienced influenza-like illness episodes during
      the follow-up period. The use of an adjuvanted vaccine against pandemic influenza
      A (H1N1) appears to be an effective and safe preventive strategy, showing a
      prevalence of both local and systemic adverse reactions not very different from
      that seen after vaccination with non-adjuvanted seasonal influenza vaccine.
      Despite this finding, vaccination coverage among HCWs remains very low,
      suggesting the need to implement educational campaigns directed to groups with
      lower coverage rates.

PMID- 21199701
TI  - Effectiveness of the pandemic influenza A/H1N1 2009 monovalent vaccine in Korea.
AB  - The 2009 influenza pandemic was caused by a novel triple-reassortant influenza
      A/H1N1 virus that was further recombined with a Eurasian pig flu virus.
      Vaccination is a key countermeasure for disease; however, little data assessing
      vaccine effectiveness (VE) against the pandemic H1N1 virus are available. We
      conducted a matched case-control study to assess effectiveness of the 2009
      influenza A/H1N1 monovalent vaccine against laboratory-confirmed, medically
      attended influenza patients. Subjects included in the study were >= 10 years of
      age and were treated at five university hospitals in the Republic of Korea (ROK)
      from December 2009 through March 2010. For subjects visiting outpatient clinics
      with influenza-like illness (ILI), real time reverse transcription polymerase
      chain reaction (rRT-PCR) was used to diagnose 2009 H1N1 influenza virus
      infection. Subjects with positive rRT-PCR were classified as cases, while those
      testing negative were controls. A valid vaccination corresponded to >= 14 days
      between receiving a dose of vaccine and symptom onset. Overall, 416 ILI subjects
      were analyzed, and 60 (14.4%) were vaccinated with the 2009 influenza A/H1N1
      monovalent vaccine. The overall VE against pandemic 2009 A/H1N1 virus illness
      after adjustment for age group and presence of chronic medical conditions was
      73.4% (95% confidence interval [CI]=49.1-86.1%). Both vaccine formulations
      (unadjuvanted and MF-59 adjuvanted) showed a statistically significant VE. In
      conclusion, the 2009 influenza A/H1N1 monovalent vaccine was substantially
      protective against pandemic influenza in the ROK during the 2009-2010 season.

PMID- 21199702
TI  - Hsp70 vaccination-induced antibodies recognize B cell epitopes in the cell wall
      of Mycobacterium avium subspecies paratuberculosis.
AB  - Mycobacterium avium subspecies paratuberculosis (MAP) causes a chronic intestinal
      infection of ruminants and has been associated with the etiology of human Crohn's
      disease. A MAP Hsp70/DDA subunit vaccine previously showed a significant
      reduction in fecal shedding of MAP in cattle, concomitant with pronounced
      antibody production against MAP Hsp70, rather than T cell reactivity. Our
      hypothesis is that if Hsp70-specific antibodies are able to confer protection,
      the first requisite would be that the Hsp70 molecule is accessible for antibodies
      in intact MAP bacteria. In the current study monoclonal antibodies identified MAP
      Hsp70 B cell epitopes. Two linear epitopes were also recognized by antibodies of
      vaccinated calves and goats. These epitopes showed to be accessible by antibodies
      in the bacterial cell wall and in intestinal lesional tissue during natural
      infection. These results indicate that vaccination-induced antibodies can bind
      intact bacteria and have the potential to contribute to the protective effect of
      Hsp70/DDA subunit vaccination against bovine paratuberculosis.

PMID- 21199703
TI  - Carriage of Haemophilus influenzae among Brazilian children attending day care
      centers in the era of widespread Hib vaccination.
AB  - Haemophilus influenzae type b vaccine was introduced into the Immunization
      Program of Brazil in 1999 and no study has evaluated the impact of Hib
      vaccination in H. influenzae carriage so far. In June 2010, Brazil introduced the
      10-valent pneumococcal nontypeable H. influenzae (NTHi) conjugate vaccine (PHiD
      CV). We investigated the prevalence of encapsulated H. influenzae and NTHi
      isolates in nasopharyngeal samples of 1192 children attending day-care centers in
      Goiania, central Brazil. H. influenzae carriage rate was 32.1% and 38.4% of them
      carried beta-lactamase TEM-1 gene. Serotype f (4.6%) was the most frequent
      encapsulated isolate, type b was recovered in only 0.7% and carriage rate of NTHi
      was 23.3%. Recurrent acute otitis media and NTHi were independently associated
      with colonization by beta-lactamase producing H. influenzae. Changes in frequency
      of H. influenzae carriage isolates should be carefully monitored to assess the
      impact of the PHiD-CV on NTHi carriage in young children.

PMID- 21199704
TI  - A phase 1 study of a meningococcal native outer membrane vesicle vaccine made
      from a group B strain with deleted lpxL1 and synX, over-expressed factor H
      binding protein, two PorAs and stabilized OpcA expression.
AB  - This phase I clinical trial assessed the safety and immunogenicity of a native
      outer membrane vesicle (NOMV) vaccine prepared from an lpxL1(-) synX(-) mutant of
      strain 8570(B:4:P1.19,15:L8-5) of Neisseria meningitidis. Additional mutations
      enhance the expression of factor H binding protein variant 1 (fHbp v.1),
      stabilize expression of OpcA and introduce a second PorA (P1.22,14). Thirty-six
      volunteers were assigned to one of four dose groups (10, 25, 50 and 75 mcg, based
      on protein content) to receive three intramuscular injections at six week
      intervals with aluminum hydroxide adjuvant. Specific local and systemic adverse
      events were solicited by diary and at visits on days 2, 7, and 14 after each
      vaccination. Blood chemistries, complete blood count, and coagulation studies
      were measured on each vaccination day and again 2 and 14 days later. Blood for
      ELISA and serum bactericidal assays was drawn two and six weeks after each
      vaccination. The proportion of volunteers who developed a fourfold or greater
      increase in bactericidal activity to the wild type parent of the vaccine strain
      at two weeks after the third dose was 27 out of 34 (0.79, 95% C.I. 0.65-0.93).
      Against four other group B strains the response rate ranged from 41% to 82%
      indicating a good cross reactive antibody response. Depletion assays show
      contributions to bactericidal activity from antibodies to lipooligosaccharide
      (LOS), fHbp v.1 and OpcA.

PMID- 21199705
TI  - Tick-borne encephalitis: the impact of epidemiology, changing lifestyle, and
      environmental factors. Conference report of the 12th Annual Meeting of the
      International Scientific Working Group on Tick-Borne Encephalitis (ISW-TBE).

PMID- 21199706
TI  - A novel prototype device for electroporation-enhanced DNA vaccine delivery
      simultaneously to both skin and muscle.
AB  - Electroporation (EP) of either muscle or skin has proven to be an efficient
      method for increasing DNA-based vaccine delivery and immunogenicity in small and
      large animals. Previous comparative studies in large animals suggest that
      intramuscular (i.m.) DNA EP delivery appears to favor cellular immunity, while
      intradermal (i.d.) EP delivery may favor humoral immunity. While current EP
      devices are primarily designed either for i.m. or i.d. delivery, we developed a
      novel prototype Dual-Depth Device (DDD) for EP-mediated simultaneous i.d. and
      i.m. delivery of DNA-based vaccines with an attempt to elicit superior antibody
      and cellular immune responses. We performed comparisons of DDD EP delivery with
      standard i.d. EP, standard i.m. EP, and combined delivery of i.d. and i.m. EP at
      separate sites, for the ability to induce antigen-specific immune responses. In a
      guinea pig model using a SynConTM DNA vaccine encoding the influenza virus H5
      hemaglutinin (H5HA), vaccination via DDD or combined delivery induced higher
      antibody titers than via either i.d. or i.m. delivery alone. In a mouse model
      using a DNA vaccine encoding the nucleoprotein (NP) of influenza H1N1, the
      resulting trend of antibody responses was similar to that detected in guinea pig
      study. Importantly, cellular immune responses in the DDD or combined delivery
      groups were significantly stronger than that in either i.d. or i.m. delivery
      groups. We conclude that EP-mediated DNA-based vaccine delivery to both skin and
      muscle is superior to delivery to either tissue alone for induction of antigen
      specific antibody and cellular immunity.

PMID- 21199708
TI  - Computerized cognitive remediation treatment for substance abuse disorders.

PMID- 21199707
TI  - Adenovirus particles that display the Plasmodium falciparum circumsporozoite
      protein NANP repeat induce sporozoite-neutralizing antibodies in mice.
AB  - Adenovirus particles can be engineered to display exogenous peptides on their
      surfaces by modification of viral capsid proteins, and particles that display
      pathogen-derived peptides can induce protective immunity. We constructed viable
      recombinant adenoviruses that display B-cell epitopes from the Plasmodium
      falciparum circumsporozoite protein (PfCSP) in the major adenovirus capsid
      protein, hexon. Recombinants induced high-titer antibodies against CSP when
      injected intraperitoneally into mice. Serum obtained from immunized mice
      recognized both recombinant PfCSP protein and P. falciparum sporozoites, and
      neutralized P. falciparum sporozoites in vitro. Replicating adenovirus vaccines
      have provided economical protection against adenovirus disease for over three
      decades. The recombinants described here may provide a path to an affordable
      malaria vaccine in the developing world.

PMID- 21199709
TI  - Increased glutamatergic synaptic transmission in the amygdala of drug abusers.

PMID- 21199710
TI  - Blue-blocking IOLs vs. short-wavelength visible light: hypothesis-based vs.
      evidence-based medical practice.

PMID- 21199711
TI  - Deep anterior lamellar keratoplasty as an alternative to penetrating keratoplasty
      a report by the american academy of ophthalmology.
AB  - OBJECTIVE: To review the published literature on deep anterior lamellar
      keratoplasty (DALK) to compare DALK with penetrating keratoplasty (PK) for the
      outcomes of best spectacle-corrected visual acuity (BSCVA), refractive error,
      immune graft rejection, and graft survival. METHODS: Searches of the peer
      reviewed literature were conducted in the PubMed and the Cochrane Library
      databases. The searches were limited to citations starting in 1997, and the most
      recent search was in May 2009. The searches yielded 1024 citations in English
      language journals. The abstracts of these articles were reviewed, and 162
      articles were selected for possible clinical relevance, of which 55 were
      determined to be relevant to the assessment objective. RESULTS: Eleven DALK/PK
      comparative studies (level II and level III evidence) were identified that
      compared the results of DALK and PK procedures directly; they included 481 DALK
      eyes and 501 PK eyes. Of those studies reporting vision and refractive data,
      there was no significant difference in BSCVA between the 2 groups in 9 of the
      studies. There was no significant difference in spheroequivalent refraction in 6
      of the studies, nor was there a significant difference in postoperative
      astigmatism in 9 of the studies, although the range of astigmatism was often
      large for both groups. Endothelial cell density (ECD) stabilized within 6 months
      after surgery in DALK eyes. Endothelial cell density values were higher in the
      DALK groups in all studies at study completion, and, in general, the ECD
      differences between DALK and PK groups were significant at all time points at 6
      months or longer after surgery for all of the studies reporting data.
      CONCLUSIONS: On the basis of level II evidence in 1 study and level III evidence
      in 10 studies, DALK is equivalent to PK for the outcome measure of BSCVA,
      particularly if the surgical technique yields minimal residual host stromal
      thickness. There is no advantage to DALK for refractive error outcomes. Although
      improved graft survival in DALK has yet to be demonstrated, postoperative data
      indicate that DALK is superior to PK for preservation of ECD. Endothelial immune
      graft rejection cannot occur after DALK, which may simplify long-term management
      of DALK eyes compared with PK eyes. As an extraocular procedure, DALK has
      important theoretic safety advantages, and it is a good option for visual
      rehabilitation of corneal disease in patients whose endothelium is not
      compromised.

PMID- 21199712
TI  - Diabetes and keratoconus.

PMID- 21199713
TI  - Endothelial keratoplasty.

PMID- 21199716
TI  - Iris melanoma.

PMID- 21199717
TI  - Keratoprosthesis sterile vitritis.

PMID- 21199718
TI  - Artifacts associated with spectral-domain OCT.

PMID- 21199719
TI  - Rituximab for uveitis.

PMID- 21199720
TI  - Visual axis opacification in children.

PMID- 21199721
TI  - Entropion.

PMID- 21199723
TI  - Entropion.

PMID- 21199725
TI  - Reactive oxygen species-activated p38/ERK 1/2 MAPK signaling pathway in the
      Mycobacterium bovis bacillus Calmette Guerin (BCG)-induced CCL2 secretion in
      human monocytic cell line THP-1.
AB  - BACKGROUND AND AIMS: CCL2 plays an important role in mycobacterial infection by
      inducing leukocyte recruitment and activation. Here we assess the role of
      reactive oxygen species (ROS) in the secretion of the CCL2 and the activation of
      mitogen-activated protein kinases (MAPKs) by human monocytic cells infected with
      Mycobacterium bovis bacillus Calmette Guerin (BCG). METHODS: CCL2 mRNA and
      protein expression were measured by reverse transcriptase polymerase chain
      reaction (RT-PCR), quantitative PCR and ELISA. Kinase phosphorylation was
      determined by immunoblotting. RESULTS: Treatment of human monocytic cells with M.
      bovis BCG activated rapid superoxide generation. mRNA expression of CCL2 was
      increased in M. bovis BCG-infected monocytic cells, and this increase was
      abrogated by administration of the nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase inhibitor diphenyleneiodonium (DPI). Importantly, M. bovis BCG
      induced CCL2 protein secretion was also inhibited by the NADPH oxidase inhibitor
      DPI, the selective inhibitor of NADPH oxidase apocynin, the mitochondrial
      electron transfer chain subunit I inhibitor rotenone and H(2)O(2) scavenging
      enzyme catalase, indicating that the inhibition is through the NADPH/ROS pathway.
      Analysis of downstream signals showed that inhibition of NADPH oxidase inhibited
      M. bovis BCG-induced phosphorylation of MAPK (extracellular signal-regulated
      kinase (ERK) 1/2 and p38). CONCLUSIONS: These results strongly suggest that NADPH
      oxidase-derived ROS-mediated activation of p38 and ERK 1/2 is essential for the
      M. bovis BCG-induced CCL2 production.

PMID- 21199726
TI  - Expression of discoidin domain receptors (DDR2) in alcoholic liver fibrosis in
      rats.
AB  - BACKGROUND AND AIMS: We undertook this study to evaluate the expression of
      discoidin domain receptor 2 (DDR2) and its relationship with alcoholic liver
      fibrosis. METHODS: Liver fibrosis was induced by intragastric administration of
      alcohol in 30 rats. Pathological changes and ultrastructure of the liver were
      studied. The expression of DDR2 mRNA and protein was detected by RT-PCR and
      Western blot, respectively, at weeks 12, 16 and 20 during the alcohol
      administration. RESULTS: In the control group (con) (n = 10), DDR2 mRNA
      expression and DDR2 protein were 1.02 +/- 0.13 (con ratio x10-3) and 0.32 +/-
      0.03, respectively. In the study groups there was a progressive increase in DDR2
      mRNA expression from weeks 12, 16 and 20 (3.64 +/- 1.69, 8.34 +/- 2.39, 15.73 +/-
      4.57 con ratio x10-3, p <0.05). There was also a progressive increase in DDR2
      protein from weeks 12-20 (0.48 +/- 0.05, 0.74 +/- 0.06 and 0.99 +/- 0.05, p
      <0.05). The mean DDR2 mRNA and protein in the three study groups was higher than
      in the control group (p <0.01). The expressions of DDR2 mRNA and protein were
      positively correlated with collagen type I, III and IV in liver tissues as well
      as with the serum biomarkers of liver fibrosis, collagen type III, hyaluronic
      acid, collagen type IV and laminin (p <0.01). CONCLUSIONS: The expression of DDR2
      in this alcohol-induced liver fibrosis rat model is enhanced. The expression of
      DDR2 is closely associated with collagens in the fibrotic liver tissues.

PMID- 21199727
TI  - Correlation of plasma and synovial fluid adiponectin with knee osteoarthritis
      severity.
AB  - BACKGROUND AND AIMS: Osteoarthritis (OA) is a chronic degenerative joint disorder
      of the synovial joint characterized by loss of articular cartilage, osteophyte
      formation, and alterations of subchondral bone. The purposes of this study were
      to measure adiponectin concentrations in plasma and synovial fluid of patients
      with knee OA and to analyze the correlation of adiponectin levels with disease
      severity. METHODS: Seventy six OA patients (mean age 69.8 +/- 1.1 years) and 24
      healthy controls (mean age 71.2 +/- 1.5 years) were enrolled in this study. OA
      grading was performed using the Kellgren-Lawrence (KL) criteria by evaluating x
      ray changes observed in anteroposterior knee radiography. Adiponectin levels in
      plasma and synovial fluid were determined by commercial enzyme-linked
      immunosorbent assay. RESULTS: Plasma levels of adiponectin were higher in OA
      patients compared to healthy individuals, but the difference did not reach
      statistical significance (2428.0 +/- 245.1 vs. 2030.3 +/- 399.4 ng/mL, p = 0.4).
      Adiponectin levels in plasma were remarkably higher with regard to paired
      synovial fluid (2428.0 +/- 245.1 vs. 301.3 +/- 44.9 ng/mL, p <0.001).
      Additionally, adiponectin concentrations in plasma and synovial fluid showed
      significant inverse correlation with disease severity evaluated by KL grading
      criteria (r = -0.68, p <0.001 and r = -0.47, p <0.001, respectively). Further
      analysis showed that plasma adiponectin levels positively correlated with
      synovial fluid adiponectin levels (r = 0.71, p <0.001). CONCLUSIONS: Adiponectin
      levels in both plasma and synovial fluid decreased significantly as the severity
      of OA increased. These findings suggested that adiponectin may play a protective
      role in OA. More studies are warranted to gain insight into the potential utility
      of adiponectin as a biochemical determinant of disease progression and prognosis.

PMID- 21199728
TI  - Estrogen receptor beta genetic variants and combined oral contraceptive use as
      relates to the risk of hypertension in Chinese women.
AB  - BACKGROUND AND AIMS: Estrogen receptor beta (ESR2) plays an important role in
      cardiovascular physiology and blood pressure regulation, whereas estrogens may
      influence gene expression, growth, and cellular differentiation in target tissues
      by activating estrogen receptors. This study aims to investigate the association
      between common genetic variants of ESR2 gene and the risk of hypertension and to
      explore the combined effected of ESR2 variants and combined oral contraceptive
      (COC) use for hypertension risk. METHODS: A population-based case-control study
      was conducted in 621 female hypertensive patients and 621 female normotensive
      controls. RESULTS: ESR2 G1082A heterozygote genotype (GA) was in significant
      relationship with hypertension (crude odds ratio [OR] = 1.38, 95% CI: 1.09-1.76;
      adjusted odds ratio [OR] = 1.38, 95% CI: 1.09-1.76). No association was observed
      for ESR2 G1730A polymorphism. Furthermore, the joint effects of the heterozygote
      of G1082A polymorphism (heterozygote model: GG/AA vs. GA) and cumulative COC use
      time >=15 years significantly increased the risk of hypertension [adjusted odds
      ratio (OR) = 2.19, 95% CI: 1.49-3.24], and the interaction effects between those
      two risk factors were significant (p = 0.0001). CONCLUSIONS: The heterozygote GA
      genotype of ESR2 gene G1082A polymorphism may be a risk genotype for hypertension
      in Chinese women, and the GA genotype (heterozygote model: GG/AA vs. GA) of
      G1082A locus together with COC use simultaneously contributed to hypertension
      development.

PMID- 21199729
TI  - Vascular endothelial growth factor-C associated with computed tomography used in
      the diagnosis of lymph node metastasis of bladder carcinoma.
AB  - BACKGROUND AND AIMS: Vascular endothelial growth factor C (VEGF-C) has been
      demonstrated to stimulate the growth of lymphatic vascular endothelium. The
      purpose of this study is to determine whether VEGF-C associated with computed
      tomography (CT) has a relationship with lymph node metastasis in bladder
      transitional cell carcinoma (BTCC). METHODS: One hundred twenty seven cases of
      BTCC were studied: first, both plain and enhanced CT scans of abdomen and pelvis
      were performed preoperatively; second, VEGF-C protein expressions in tumor cells
      were tested by immunohistochemistry postoperatively; and finally, detailed
      pathological findings for lymph node metastasis were recorded. RESULTS: VEGF-C
      expressions in tumor bladder cells were significantly higher than those in normal
      bladder epithelium. In the group of BTCC-positive, VEGF-C was significantly
      correlated with lymph node metastasis (p <0.01). Sensitivity, specificity and
      accuracy of VEGF-C in the diagnosis of lymph node metastasis of bladder carcinoma
      were 87.0, 67.9, and 74.8%, respectively. Sensitivity, specificity and accuracy
      of CT were 47.8, 80.2, and 68.5%, respectively. When VEGF-C visually correlated
      with CT scan in the detection of lymph node metastasis, sensitivity was 91.3%;
      specificity was 84.0% and accuracy was 86.6%. CONCLUSIONS: Positive VEGF-C was
      significantly correlated with lymph node metastasis of bladder carcinoma. VEGF-C
      expression in biopsy specimens may be beneficial in predicting pelvic lymph
      nodes. It can improve accuracy when combined with CT.

PMID- 21199730
TI  - Role of immature microvessels in assessing the relationship between CT perfusion
      characteristics and differentiation grade in lung cancer.
AB  - BACKGROUND AND AIMS: We undertook this study to investigate the association
      between CT perfusion characteristics and differentiation grade in lung cancer, as
      well as the pathological basis of this association. METHODS: Seventy three
      patients received CT perfusion scan and pathological biopsy, and 30 of them were
      available for comparison. In these 30 patients, the region detected with
      pathological biopsy was consistent with the region of interest of CT perfusion.
      We compared the CT perfusion parameters [blood volume (BV), blood flow (BF), and
      peak enhancement intensity (PEI)] of these patients with their differentiation
      grade of lung cancer and microvessel count, which includes microvessel density
      (MVD) and maturity. RESULTS: The lower the grade of differentiation of the
      nodules, the more drastically perfusion parameters decreased. BF was best
      correlated with differentiation grade (r = -0.845, p = 0.000), compared to BV and
      PEI (r = -0.674, -0.438, p = 0.000, 0.015, respectively). Poorly differentiated
      lung cancer showed significantly higher density of immature microvessels than
      that of highly differentiated lung cancer (p = 0.001). There was a correlation
      between the differentiation grade and the density of immature microvessels (r =
      0.669, p = 0.000), but there was no significant correlation with MVD and the
      density of mature microvessel (r = 0.345, 0.269, p = 0.062, 0.150, respectively).
      The density of immature microvessels still increased with declining BF value in
      the nodules when the grade of differentiation of lung cancer was under control (r
      = -0.748, p = 0.000). CONCLUSIONS: CT perfusion characteristics are helpful to
      differentiate lung cancer differentiation, pathologically basing on the density
      of immature microvessels rather than MVD.

PMID- 21199731
TI  - Predictive value of neutrophil to lymphocyte ratio in outcomes of patients with
      acute coronary syndrome.
AB  - BACKGROUND AND AIMS: Acute coronary syndrome (ACS) is associated with many
      hereditary and acquired predisposing factors. It has been recently shown that
      inflammation may play a role in myocardial ischemia. Hence, the white blood cell
      (WBC) count provides a simple and inexpensive method for assessment of
      inflammatory status in patients with ACS. An elevated WBC count has been
      associated with cardiovascular risk, but which leukocyte subtype carries this
      risk is uncertain. The aim of this study was to investigate the utility of
      admission neutrophil/lymphocyte ratio (NLR) in predicting the likelihood of poor
      outcomes in patients with ACS. METHODS: A total of 300 consecutive patients
      admitted to the Internal Medicine Department, Sohar Hospital, Oman with the
      diagnosis of ACS from June 2008 to May 2009 were included in this study. Patients
      were divided into tertile groups according to the NLR. The primary end point was
      all-cause in-hospital mortality at the end of 30 days. RESULTS: The mean age of
      patients included in this cohort was 61 years, with 63% of male patients. The
      mortality in the three groups based on NLR was 4, 10 and 19%, in the low-, middle
      and high-risk groups, respectively (p <0.003; chi2 test). CONCLUSIONS: Admission
      NLR is clearly an independent predictor of all-cause mortality in patients with
      ACS.

PMID- 21199732
TI  - Impairment in immunomodulatory function of mesenchymal stem cells from multiple
      myeloma patients.
AB  - BACKGROUND AND AIMS: Abnormality of immune regulation exists in multiple myeloma
      (MM). Mesenchymal stem cells (MSCs), a key regulator for immunomodulatory
      function, have decreased osteogenic potential in MM patients. Here we
      investigated the immunomodulatory function of MSCs from MM patients (MM-MSCs) and
      its relationship with decreased osteogenic potential. METHODS: Real-time PCR was
      performed to detect the cytokines expressed in MM-MSCs (n = 22) and MSCs from
      normal donors (ND-MSCs, n = 11). Lymphocyte proliferative assay was used to
      detect the effect of MSCs on T cell proliferation. The effect of MSCs on T-cell
      cycle and T-cell activation markers expression were analyzed by flow cytometry.
      Flow cytometry and Western blot were used to detect apoptosis of T cells.
      Influence of T cells on osteogenic potential of MSCs was detected. RESULTS: MM
      MSCs exhibited increased expression of TGF-beta1, IL-6, IL-3, TNF-alpha and RANKL
      and decreased expression of TGF-beta2, TGF-beta3 and FasL. The inhibitory effect
      of MM-MSCs on T.cell proliferative ability was attenuated. ND-MSCs silence more T
      cells in G0/G1 phase than MM-MSCs. The apoptosis-promoting effect of MM-MSCs on T
      cells seemed to be dampened. Expression of T-cell activation markers was
      significantly inhibited by ND-MSCs. T cells from normal donors possessed the
      ability to promote osteoblastic differentiation of ND-MSCs, but this ability of T
      cells both directly from MM patients and co-cultured with MM-MSCs was impaired.
      CONCLUSIONS: MSCs from MM patients showed impaired immunoinhibitory capability on
      T cells, which in turn lose the ability to stimulate osteogenesis of MSCs.

PMID- 21199733
TI  - Variants of arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene and
      risk of coronary heart disease: A meta-analysis.
AB  - BACKGROUND AND AIMS: Previous studies indicated that the arachidonate 5
      lipoxygenase-activating protein (ALOX5AP) gene polymorphisms are associated with
      risk of coronary heart disease (CHD). However, other studies have yielded
      contradictory results. This meta-analysis investigated the relationship between
      variants of arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene and
      CHD. METHODS: We identified all studies published before January 2010 through
      computer-based searches of PubMed, EMBASE, Google Scholar databases, and CNKI
      (Chinese National Knowledge Infrastructure). Data were extracted by two authors
      and pooled odds ratio (OR) and 95% confidence interval (CI) were calculated.
      RESULTS: In this meta-analysis, HapA haplotype (rs17222814G-rs10507391T
      rs4769874G-rs9551963A) was associated with myocardial infarction (MI) (OR = 1.37,
      95% CI: 1.02-1.82). Regarding the HapB haplotype (rs17216473A-rs10507391A-
      rs9315050A- rs17222842G), there was a significant association with CHD (OR =
      1.33, 95% CI: 1.10-1.62). For the rs17222814, rs10507391, rs4769874, rs9551963,
      rs17216473, rs9315050 and rs9579646 polymorphisms, there were no associations
      with CHD. For the rs17222842 polymorphism, there was a marginal association with
      the risk of CHD (OR = 1.17, 95% CI: 1.00-1.36). CONCLUSIONS: In this meta
      analysis, the HapB haplotype and rs1722842 polymorphism in ALOX5AP gene were
      associated with CHD, and the HapA haplotype was associated with risk of MI. The
      HapB haplotype may be a predictor to the risk of CHD.

PMID- 21199734
TI  - Functional impact of coronary stenosis observed on coronary computed tomography
      angiography: Comparison with 13N-ammonia PET.
AB  - BACKGROUND AND AIMS: We undertook this study to evaluate the functional impact of
      coronary abnormalities in patients with suspected coronary artery disease (CAD)
      by means of integrated positron emission tomography (PET) and coronary computed
      tomography angiography (CCTA) scan obtained on a hybrid state-of-the-art PET/CT
      scanner. METHODS: We studied 29 consecutive, patients with a clinically suspected
      intermediate risk for CAD, using a hybrid PET/CT 64 slice scanner. During a
      single scanning session, CCTA was performed for coronary anatomy evaluation, and
      a rest/adenosine stress (13)N-ammonia PET was performed for myocardial perfusion
      assessment in 3D mode with CT attenuation correction. RESULTS: Twenty four
      (82.7%) patients had atherosclerosis detected by CCTA; 15 patients had
      significant (>=50%) coronary stenoses and all 15 patients showed ischemia by PET;
      moreover, 10/15 patients had a Summed Stress Score >12.20/24 and 83.3% patients
      with atherosclerosis detected by CCTA showed ischemia by PET. Two of five
      patients with normal coronary arteries showed ischemia by PET. CCTA agreement in
      positive identification of PET ischemia was 91% and agreement in ruling out
      ischemia was 43%; PET agreement in detecting CCTA atherosclerosis was 83%, and
      agreement in ruling it out was 60%. CONCLUSIONS: We found a strong relation
      between significant coronary stenosis identified by CCTA and ischemia by PET.
      However, in cases with low-grade stenosis, PET scan can assess the functional
      significance of atherosclerotic abnormalities.

PMID- 21199735
TI  - Role of ezetimibe in the prevention of cardiovascular disease: absence of
      evidence.
AB  - Ezetimibe is a lipid-lowering agent that inhibits intestinal absorption of
      dietary cholesterol. It substantially lowers low-density lipoprotein cholesterol
      levels when used alone or in combination with statins. Although there is a
      growing push for the continued use of ezetimibe for the prevention of
      cardiovascular disease, ezetimibe studies available so far are inconsistent,
      without allowing use of the drug with confidence.

PMID- 21199736
TI  - Methionine sulfoximine may improve inflammation in autism, a novel hypothesized
      treatment for autism.

PMID- 21199737
TI  - Reflections on the mode of functioning of endocrine systems.
AB  - The concept of hormones as chemical messengers that transmit information from one
      organ to other organs by way of circulating blood has implications that have not
      been made explicit. In this paper the concept is analyzed and is shown to be
      inconsistent with many observations. The previously proposed concepts of hormone
      multifunctionalities, hormonal multisignal messages, and the conversion of
      hormones into other hormones are shown to clarify conflicting observations as
      well as the congruous mode of functioning of endocrine systems with
      multifunctional hormones. A strategy is proposed for identifying the compositions
      and functions of the diverse multisignal messages conveyed by any hormone. The
      information so obtained could be useful for the development of more selective
      hormonal therapies.

PMID- 21199738
TI  - Stroke during pregnancy and puerperium: clinical perspectives.
AB  - Stroke is a rare but potentially devastating disease during pregnancy and
      puerperium. Pregnancy is well recognized as a risk factor for stroke. Accurate
      and timely identification of stroke is crucial for clinical practice. However,
      the optimal management of pregnant women with stroke remains a clinical
      challenge. Thus, identification of risk factors and modification of underlying
      pathophysiological mechanisms would be of great value for stroke prevention and
      management. In terms of pharmacological intervention, it is important to
      determine the safety of a drug for mothers, their fetuses, and nursing infants.
      Neurologists treat non-pregnant patients without those considerations. Based on
      the above issues, we have reviewed the current literature and summarized
      clinically relevant issues for obstetricians and neurologists in treating stroke
      during pregnancy and puerperium.

PMID- 21199739
TI  - Robot-assisted laparoscopic staging surgery for endometrial cancer--a preliminary
      report.
AB  - OBJECTIVE: The robotic surgical system is reported to overcome some technical
      difficulties in traditional laparoscopic hysterectomy. This study aimed to
      evaluate the feasibility and surgical outcomes of a robotic surgery program for
      endometrial cancer. MATERIALS AND METHODS: Patients with endometrial cancer with
      the intention to receive treatment using robot-assisted laparoscopic staging
      surgery were recruited in a university hospital from July 2007 to August 2008.
      All of these surgeries were performed with the da Vinci system. RESULTS: Six
      patients (mean age, 47.5 +/-1.4 years; mean body mass index, 26.2 +/-3.5 kg/m(2))
      were enrolled and completed robot-assisted laparoscopic staging surgery. The
      robot docking time was 45.0 +/-13.6 minutes and the robot-assisted operation time
      was 200.3 +/-30.0 minutes. The mean estimated blood loss was 180.0 +/-147.6 mL.
      The mean number of lymph nodes retrieved was 23.2 +/-7.4. No laparoconversion and
      no intraoperative or postoperative complications occurred. All patients were
      alive and free of disease up to the date of this report, at a median follow-up of
      6.5 months (range, 5-17 months). CONCLUSION: Robot-assisted laparoscopic staging
      surgery is a feasible treatment and helps overcome the technical limitations in
      conventional laparoscopy for endometrial cancer.

PMID- 21199740
TI  - The effect of HPV infection on a couple's relationship: a qualitative study in
      Taiwan.
AB  - OBJECTIVE: The purpose of this study is to explore the effect of human
      papillomavirus (HPV) on the sexual lives of women and their partners. MATERIALS
      AND METHODS: Twenty oncogenic or high-risk HPV infected cases were collected via
      purposive sampling. At a tertiary medical center in Taipei, 20 women underwent a
      2-hour in-depth interview. The content of each interview was analyzed
      qualitatively regarding (1) effect of HPV infection on a couple's relationship;
      (2) effect of HPV infection on sexual life; (3) partner support and social
      support; (4) myths about love and marriage; and (5) sexual myths. RESULTS: The
      better a couple's relationship, the less these patients struggled to confront the
      issue (HPV infection). Most patients urged partners to have check-ups and advised
      friends about Pap smear tests. Couple relationships were generally not affected
      by HPV infection, unlike their sexual lifestyles. Most patients fulfilled the
      traditional Chinese female role of maintaining the relationship. However, due to
      the physical and psychosocial discomfort of treatment and fear of infection, some
      had no desire for sex, while others lessened their sex frequency. Most patients
      received very little support from their partner, family, and friends. The
      relationship quality was affected by marital and sexual myths held by patients.
      CONCLUSION: Cervical HPV infection has a negative effect on women's sexual
      relationships. Thus, more attention from health care providers is required.

PMID- 21199741
TI  - Factors that influence changes in mammographic density with postmenopausal
      hormone therapy.
AB  - OBJECTIVE: To evaluate the relationship between mammographic density and clinical
      factors in postmenopausal women using hormone therapy (HT). MATERIALS AND
      METHODS: Retrospective study of 467 postmenopausal women who received continuous
      estrogen or estrogen-progestin HT and had regular mammography between 1994 and
      2001. A detailed clinical history was recorded, including age at start of HT, age
      at menopause, years from onset of menopause to start of HT, body mass index
      (BMI), and duration and regimens of HT. RESULTS: After adjustment for the effects
      of other variables, age at the start of HT and BMI were inversely associated with
      breast density (p = 0.0025 and < 0.001, respectively). In contrast, duration of
      HT was positively related to mammographic density (p<0.001). Although the mean
      density was significantly increased after 4 years of HT in women receiving
      combined HT compared with those using estrogen alone, after adjustment for the
      effects of other variables, the correlation between mammographic density and
      regimen of HT (combined HT vs. estrogen alone) did not reach the significance
      level of 0.05. CONCLUSION: Higher mammographic density was associated with longer
      use of HT, especially in younger post-menopausal women and those with lower BMI.

PMID- 21199742
TI  - Caffeic acid induces apoptosis in human cervical cancer cells through the
      mitochondrial pathway.
AB  - OBJECTIVE: The anti-proliferation effect of caffeic acid (3,4-dihydroxycinnamic
      acid), isolated from Ocimum gratissimum Linn, on human cervical cancer cells
      (HeLa cells) was examined to elucidate the associated mechanism and death mode.
      MATERIALS AND METHODS: Flow cytometry showed that caffeic acid treatment results
      in dramatically increased apoptosis of HeLa cells. Western blot analysis revealed
      that caffeic acid activates various processed caspases. RESULTS: Caffeic acid
      significantly reduced proliferation of HeLa cells in a concentration-dependent
      manner. Morphological evidence of apoptosis, including nuclei fragmentation was
      clearly observed 24 and 48 hours after exposure to caffeic acid (1 mM and 10 mM)
      by flow cytometry. Time-dependent inhibition was also observed. Caffeic acid
      decreased levels of uncleaved caspase-3 and Bcl-2, and induced cleaved caspase-3
      and p53. CONCLUSION: Caffeic acid induces apoptosis by inhibiting Bcl-2 activity,
      leading to release of cytochrome c and subsequent activation of caspase-3,
      indicating that caffeic acid induces apoptosis via the mitochondrial apoptotic
      pathway. This also suggests that caffeic acid has a strong anti-tumor effect and
      may be a promising chemopreventive or chemotherapeutic agent.

PMID- 21199743
TI  - Multiple repeated cesarean deliveries: operative complications in the fourth and
      fifth surgeries in urgent and elective cases.
AB  - OBJECTIVE: To evaluate the maternal and neonatal risk related with multiple
      repeated cesarean sections. MATERIALS AND METHODS: A case control study was
      conducted in a single tertiary maternity and children's center. The outcome of a
      study group including 122 pregnant women undergoing cesarean section for the
      fourth or fifth time was compared with a control group comprising 146 women
      sectioned for the second and third time. All multiple repeated cesarean sections
      were divided into urgent and elective groups to compare the outcome measures of
      demographic, neonatal, intra- and post-operative data. RESULTS: Compared with the
      control group, the study group had significantly lower birth weights (p=0.026),
      lower Apgar scores at 1 minute (p=0.0001) and 5 minutes (p=0.042), higher numbers
      of fetal death (p=0.03), higher rate of omentum adhesions (p =0.0001) and
      peritoneal adhesions (p=0.008), increased risk of cesarean hysterectomy (p =
      0.014), increased need for transfusion (p = 0.018), and an increase in
      hospitalization days (p=0.005). Compared with the elective group, preterm birth
      incidence was higher (p = 0.01) and birth weight was lower (p=0.004) in the
      urgent group. The risk for myometrium herniation (p=0.018), need for drainage
      during operation (p=0.018), and post-operative fever (p =0.001) was also more
      common in the urgent group. CONCLUSION: Multiple repeated cesarean sections
      increase the risks for operative complications and poor perinatal outcomes.
      Patients must be informed about the related risks of multiple repeated cesarean
      sections and tubal ligation needs to be encouraged.

PMID- 21199744
TI  - A hospital-based therapeutic lifestyle program for women with metabolic syndrome.
AB  - OBJECTIVE: The aim of the present study is to evaluate the effect of a hospital
      based therapeutic lifestyle program on women with metabolic syndrome (MetS).
      MATERIALS AND METHODS: We conducted a therapeutic lifestyle program for women
      with MetS. They all received a low calorie, balanced diet and participated in a
      regular aerobic exercise program for 8 weeks. Anthropometric indices, blood
      pressure, and biochemical data were collected. A paired t test was used for
      statistical analysis. A p value of less than 0.05 was considered statistically
      significant. RESULTS: Forty-four women took part in the program. All the
      components of MetS had decreased significantly by the end of the program and 25%
      of women no longer had MetS at the end of the program. CONCLUSION: The
      therapeutic lifestyle program with diet control and regular exercise improves
      most markers of MetS except for levels of high density lipoprotein cholesterol.
      Therapeutic lifestyle intervention may be the best way of reducing the risk of
      cardiovascular disease in women with MetS.

PMID- 21199745
TI  - Hourly oral misoprostol administration for terminating midtrimester pregnancies:
      a pilot study.
AB  - OBJECTIVE: This pilot study retrospectively evaluated the outcomes of medical
      induction of termination of midtrimester pregnancies with hourly oral misoprostol
      administration. MATERIALS AND METHODS: Sixteen women with living fetuses, who had
      undergone pregnancy termination at 12-25 weeks of gestational age, were reviewed.
      The method of induction was hourly oral administration of misoprostol, given at
      doses of 200 MUg/hr for the first 12 hours and 400 MUg/hr after 12 hours until
      delivery. Data including the induction-to-delivery interval and total dosage of
      misoprostol were recorded and analyzed. RESULTS: All 16 women successfully
      underwent vaginal termination within 36 hours. The median induction-to-delivery
      interval was 12.0 hours (range, 6.3-30.9 hours), with 13 women (81.3%) undergoing
      vaginal delivery within 24 hours. The median total dosage of misoprostol was
      2,600 MUg. The most common side effect was diarrhea, which was easily relieved by
      medication. CONCLUSION: Our preliminary results show that oral administration of
      misoprostol at hourly intervals is a promising method for terminating
      midtrimester pregnancies.

PMID- 21199746
TI  - Outcomes of high initial daily doses of gonadotropin in patients with poor
      ovarian reserve.
AB  - OBJECTIVE: To evaluate the in vitro fertilization and intracytoplasmic sperm
      injection outcomes after high initial doses of follicle-stimulating hormone (FSH)
      in patients with poor ovarian reserve. MATERIALS AND METHODS: For in vitro
      fertilization/intracytoplasmic sperm injection patients younger than 40 years of
      age, 345 cycles were examined from April 2003 to April 2007. As a control, 218
      cycles received gonadotropin-releasing hormone agonist and regular initial doses
      of FSH from day 3 of the treated cycle. The remaining 127 cycles were treated
      with high initial doses of FSH with an antagonist or low doses of gonadotropin
      releasing hormone because of poor ovarian reserve. RESULTS: When higher initial
      doses of FSH were used, lower estradiol levels on the day of human chorionic
      gonadotropin injection and less mature oocytes were retrieved from the group with
      poor ovarian reserve. Clinical pregnancy rates per embryo transfer were similar
      (45.7%vs. 48.2%, p = 0.686). There was a trend of lower ongoing pregnancy rate
      per cycle (28.3%vs. 38.5%, p = 0.05) in the study compared with the control
      group. In the subgroups with high doses of FSH, neither protocol was superior in
      terms of clinical (45.5%vs. 46.2%, p=0.952) or ongoing pregnancy rates per embryo
      transfer (37.9%vs. 42.3%, p=0.695). CONCLUSION: There was no significant
      difference in clinical pregnancy rate of the two groups when good embryos were
      obtained. The group with poor ovarian reserve had lower ongoing pregnancy rates
      per cycle. For patients with expected poor ovarian response, treatment with high
      doses of FSH initially is an option.

PMID- 21199747
TI  - Deleterious effects of arsenic, benomyl and carbendazim on human endometrial cell
      proliferation in vitro.
AB  - OBJECTIVE: We aimed to investigate the effects of arsenic (As), benomyl (Ben),
      and carbendazim (Carb) on endometrial cells. MATERIALS AND METHODS: Human
      endometrial cells were obtained during diagnostic curettage. All cultured
      endometrial cells were divided into four groups: (1) 0 M (controls), (2) 10(-6)
      M, (3) 10(-5) M, (4) 10(-4) M for As, Ben and Carb. After 24 and 48 hours in
      culture, endometrial cell proliferations were assessed by diphenyltetrazolium
      bromide assay. The influences of different concentrations of As, Ben and Carb
      upon the endometrium were compared. RESULTS: During the first 24 hours, As, Ben
      and Carb appeared to have insignificant influences upon endometrial growth. After
      48 hours in culture, all three agents significantly inhibited endometrial growth.
      In As groups, cell absorption after 48 hours culture were 100% (group 1), 82.1%
      (group 2), 43.6% (group 3) and 35.3% (group 4). In Ben groups, cell absorption
      was 100% (1), 75.9% (2), 66.4% (3) and 49. 6% (4). In the Carb groups, cell
      absorption was 100% (1), 70.4% (2), 73.0% (3) and 76.7% (4). CONCLUSION: The
      agents As, Ben and Carb appear to have inhibitory effects upon endometrial cells
      after 48 hours in culture.

PMID- 21199748
TI  - Balanced reciprocal translocations detected at amniocentesis.
AB  - OBJECTIVE: To present perinatal findings, modes of ascertainment and parental
      decision in balanced reciprocal translocations detected at amniocentesis.
      MATERIALS AND METHODS: Between January 1987 and August 2010, 82 cases with a
      simple reciprocal translocation, two cases with two separate simple reciprocal
      translocations and three cases with a complex chromosome rearrangement (CCR) were
      diagnosed by amniocentesis at Mackay Memorial Hospital, Taipei, Taiwan. The 87
      cases originated from 76 families; 65 families with one case and 11 families with
      two cases. RESULTS: In the 76 families, the main modes of ascertainment included
      advanced maternal age (n=38), a previous child with an unbalanced reciprocal
      translocation (n=11), recurrent miscarriage (n = 9), abnormal maternal serum
      screening results (n = 9), elective causes (n = 5), a previous child with
      congenital anomalies (n =2) and abnormal ultrasound findings (n = 2). In these
      families, there were 17 (22.4%) de novo cases including 14 simple translocations
      and three CCRs. Of 14 de novo cases with a simple translocation, one (7.1%)
      manifested a congenital malformation, which was related to an X-autosome
      translocation, and four (28.6%) were terminated. Of three de novo CCRs, two
      manifested congenital anomalies and one was terminated. In 87 cases, additional
      aneuploidy was noted in two cases including one inherited simple translocation
      with Turner syndrome, and one de novo CCR with concomitant deletions and
      duplication. CONCLUSION: Balanced reciprocal translocations detected at
      amniocentesis may be associated with fetal anomalies in cases of concomitant
      aneuploidy, de novo X-autosome translocation or de novo CCR. Genetic counseling
      of a de novo simple reciprocal translocation at amniocentesis remains difficult
      because approximately one-fourth of the parents opt for termination of the
      pregnancy, and detailed ultrasonography and array comparative genomic
      hybridization are helpful for parental counseling under such circumstances.

PMID- 21199749
TI  - Alzheimer's disease: aging, insomnia and epigenetics.
AB  - Alzheimer's disease (AD) is the most common form of dementia. Severe memory loss,
      confusion, and impaired cognitive abilities characterize AD. It was only a
      century after Alzheimer's discovery that scientists were able to shed light on
      the mystery of its cause, but AD has also become a globally important health
      issue and the treatment of AD is a challenge for modern medicine. At present,
      there are five drugs approved in the United States for the treatment of AD,
      namely, donepezil, galantamine, rivastigmine, and tacrine (which are all
      cholinesterase inhibitors); and memantine (which is a glutamate receptor
      antagonist). However, these drugs show only modest effects on AD patients. Thus,
      new investigations are necessary for pharmacological development in AD. This
      brief review focuses on new studies that demonstrate the link between epigenetics
      and AD, and explores the possibility that insomnia may be one factor that effects
      AD.

PMID- 21199750
TI  - Chromosome 1p36 deletion syndrome: prenatal diagnosis, molecular cytogenetic
      characterization and fetal ultrasound findings.
AB  - OBJECTIVE: To present prenatal diagnosis and molecular cytogenetic
      characterization of de novo partial monosomy 1p (1p36.23->pter) and partial
      trisomy 20p (20p12.1->pter) associated with ventriculomegaly, ventricular septal
      defect and midface hypoplasia. MATERIALS, METHODS AND RESULTS: A 31-year-old,
      primigravid woman was referred for amniocentesis at 20 gestational weeks because
      of ventriculomegaly, ventricular septal defect, and midface hypoplasia.
      Amniocentesis revealed an aberrant derivative chromosome 1, or der(1). Parental
      karyotypes were normal. Spectral karyotyping analysis revealed that the der(1)
      contained a segment of chromosome 20 in the distal end of the short arm of
      chromosome 1. Array comparative genomic hybridization demonstrated an 8.4-Mb
      distal 1p deletion and a 14-Mb distal 20p duplication. The karyotype was
      46,XX,der(1)t(1;20)(p36.23;p12.1)dn. Polymorphic DNA marker analysis determined
      the paternal origin of the aberrant chromosome. The pregnancy was subsequently
      terminated. A 462-g malformed female fetus was delivered at 22 gestational weeks
      with a prominent forehead, midface hypoplasia, a flat nasal bridge, low-set ears,
      a long philtrum, a pointed chin and micrognathia. CONCLUSION: Spectral
      karyotyping, fluorescence in situ hybridization and array comparative genomic
      hybridization are useful for the prenatal investigation of the nature of a de
      novo aberrant derivative chromosome. Partial monosomy 1p (1p36.23->pter) and
      partial trisomy 20p (20p12.1->pter) are associated with ventriculomegaly,
      ventricular septal defect and midface hypoplasia on prenatal ultrasound. Prenatal
      diagnosis of ventriculomegaly, congenital heart defects and midface hypoplasia
      should alert clinicians to chromosome 1p36 deletion syndrome and prompt molecular
      cytogenetic analysis if necessary.

PMID- 21199751
TI  - Ellis-van Creveld syndrome: prenatal diagnosis, molecular analysis and genetic
      counseling.
AB  - OBJECTIVE: To present the perinatal findings and molecular genetic analysis of
      two siblings with Ellis-van Creveld (EvC) syndrome. MATERIALS, METHODS AND
      RESULTS: A 33-year-old woman, gravida 3, para 1, was referred for genetic
      counseling at 18 gestational weeks because of recurrent fetal skeletal dysplasia.
      Two years previously, she had delivered a 1,316-g dead male baby at 28
      gestational weeks with a karyotype of 46,XY, postaxial polydactyly of the hands,
      thoracic narrowness, endocardial cushion defects, transposition of the great
      arteries, shortening of the long bones, malposition of the toes, and hypoplastic
      nails. During this pregnancy, prenatal ultrasound at 18 gestational weeks
      revealed shortening of the long bones (equivalent to 15 weeks), postaxial
      polydactyly of both hands, thoracic narrowness, and endocardial cushion defects.
      The pregnancy was subsequently terminated, and a 236-g female fetus was delivered
      with a karyotype of 46,XX, postaxial polydactyly of the hands, thoracic
      dysplasia, endocardial cushion defects, shortening of the long bones, and
      malposition of the toes and hypoplastic nails. The phenotype of each of the two
      siblings was consistent with EVC syndrome. Molecular analysis of the EVC and EVC2
      genes revealed heterozygous mutations in the EVC2 gene. A heterozygous deletion
      mutation of a 26-bp deletion of c.871-2_894del26 encompassing the junction
      between intron 7 and exon 8 of the EVC2 gene was found in the mother and two
      siblings, and a heterozygous nonsense mutation of c.1195C >T, p.R399X in exon 10
      of the EVC2 gene was found in the father and two siblings. CONCLUSION: Prenatal
      sonographic identification of endocardial cushion defects in association with
      shortening of the long bones should alert clinicians to the possibility of EvC
      syndrome and prompt a careful search of hexadactyly of the hands. Molecular
      analysis of the EVC and EVC2 genes is helpful in genetic counseling in cases with
      prenatally detected postaxial polydactyly, thoracic narrowness, short limbs and
      endocardial cushion defects.

PMID- 21199752
TI  - Microvillus inclusion disease: prenatal ultrasound findings, molecular diagnosis
      and genetic counseling of congenital diarrhea.
AB  - OBJECTIVE: To present prenatal ultrasound findings and molecular diagnosis of
      microvillus inclusion disease, and to review the literature of abnormal prenatal
      ultrasound findings associated with congenital diarrhea. MATERIALS, METHODS AND
      RESULTS: A 21-year-old woman, gravida 1, para 0, had generalized bowel dilation
      of the fetus on prenatal ultrasound at 29 gestational weeks. She and her husband
      were non-consanguineous, and there was no family history of congenital diarrhea.
      Prenatal ultrasound at 29 gestational weeks revealed a honeycomb appearance of
      the bowel without ascites or intraperitoneal calcification. At 36 gestational
      weeks, polyhydramnios dilated bowel loops were observed, and a 3,355-g male baby
      was delivered with a distended abdomen. Postnatally, the neonate suffered from
      watery diarrhea and abdominal distension but there was no mechanical bowel
      obstruction. An endoscopic biopsy of the small bowel revealed intracytoplasmic
      inclusions lined by intact microvilli in the apical surface of the intestinal
      epithelial cells consistent with the diagnosis of microvillus inclusion disease.
      Mutation analysis of blood samples of the neonate and parents revealed a
      heterozygous nonsense mutation of c.445C <T, p.Q149X in exon 4 of the MYO5B gene
      in the father and proband, and a heterozygous nonsense mutation of c.1021C < T,
      p.Q341X in exon 9 of the MYO5B gene in the mother and proband. CONCLUSION:
      Prenatal sonographic identification of dilated bowel loops in association with
      polyhydramnios suggests congenital diarrhea and a differential diagnosis of
      microvillus inclusion disease in addition to congenital chloride diarrhea and
      congenital sodium diarrhea. Molecular analysis of the MYO5B gene is helpful in
      genetic counseling and prenatal diagnosis of recurrent microvillus inclusion
      disease in subsequent pregnancies.

PMID- 21199753
TI  - Use of atosiban in a twin pregnancy with extremely preterm premature rupture in
      the membrane of one twin: a case report and literature review.
AB  - OBJECTIVE: Pregnancies with extremely preterm premature rupture of membranes
      (EPPROM), especially before 20 weeks of gestation, are usually considered to be a
      termination of pregnancy. By improvement of obstetric and neonatal care, we can
      prolong the pregnancy across the threshold of survival by aggressive tocolysis.
      CASE REPORT: Using intrauterine insemination, a 32-year-old woman became pregnant
      with twins (first pregnancy). Threatened abortion occured since 9 weeks of
      gestation and EPPROM of the upper twin was noted at 18 weeks. Massive vaginal
      bleeding and vigorous uterine contractions occurred at 22 weeks. Poor control of
      preterm labor occurred using ritodrine and MgSO(4). Atosiban was applied to calm
      uterine activities. After discontinuation of atosiban at 30 weeks, the uterine
      contractions became severe again and an emergency cesarean section was performed
      to deliver two live, premature babies weighing 1,518 g and 830 g, respectively.
      Twin A was healthy, weighing 2,030 g at 35 days after birth and subsequently
      discharged. The smaller twin B was dependent on continuous positive airway
      pressure and died of pulmonary infection 120 days after birth. CONCLUSION:
      Comparing to other tocolytic agents, Atosiban has few side effects and assisted
      in prolonging a pregnancy involving twins that experienced EPPROM.

PMID- 21199754
TI  - Prenatal diagnosis and molecular cytogenetic characterization of a small
      supernumerary marker chromosome derived from chromosome 8.
AB  - OBJECTIVE: To present prenatal diagnosis and molecular cytogenetic
      characterization of a small supernumerary marker chromosome (sSMC) derived from
      chromosome 8 by multiplex ligation-dependent probe amplification (MLPA),
      fluorescence in situ hybridization (FISH), spectral karyotyping (SKY) and array
      comparative genomic hybridization (aCGH). CASE REPORT: A 42-year-old woman,
      gravida 6, para 3, underwent amniocentesis at 19 gestational weeks because of
      advanced maternal age. Amniocentesis revealed a de novo ring-shaped sSMC in all
      13 colonies of the amniocytes. The karyotype was 47,XY,+mar. The MLPA showed
      duplications of 8p11.21-specific probes. At 24 gestational weeks, level II
      ultrasound revealed a left multicystic kidney in the fetus. Other internal organs
      were unremarkable. Repeat amniocentesis revealed a karyotype of
      47,XY,+mar[25]/46,XY[2]. The sSMC was characterized by SKY and FISH, which showed
      a chromosome 8 origin of the sSMC. Oligonucleotide-based aCGH demonstrated a 4.4
      Mb duplication of 8p11.21q11.1 [arr cgh 8p11.21q11.1 (42,637,263-47,062,180)*3].
      The karyotype was 47,XY,+r(8) (p11.21q11.1)[25]/46,XY[2]. Polymorphic DNA marker
      analysis revealed no uniparental disomy for chromosome 8. The woman elected to
      continue the pregnancy and at 34 gestational weeks, a 1,820 g male baby without
      craniofacial dysmorphism was delivered. At the age of 1 month, the infant was
      apparently normal except for left multicystic kidney disease and mild
      ventriculomegaly. CONCLUSION: MLPA, SKY and aCGH are helpful in genetic
      counseling of prenatally detected sSMCs by providing the immediate information on
      the origin and the genetic contents of the sSMC.

PMID- 21199755
TI  - Partial trisomy 16p (16p12.2->pter) and partial monosomy 22q (22q13.31 ->qter)
      presenting with fetal ascites and ventriculomegaly: prenatal diagnosis and array
      comparative genomic hybridization characterization.
AB  - OBJECTIVE: To present prenatal diagnosis and array comparative genomic
      hybridization (aCGH) characterization of partial trisomy 16p (16p12.2->pter) and
      partial monosomy 22q (22q13.31->qter) presenting with fetal ascites and
      ventriculomegaly in the second trimester. CASE REPORT: A 31-year-old woman,
      gravida 2, para 1, was referred to the hospital at 20 weeks of gestation because
      of fetal ascites. Amniocentesis revealed a derivative chromosome 22. Subsequent
      parental karyotyping revealed that the father carried a balanced reciprocal
      translocation between 16p12 and 22q13. Bacterial artificial chromosome-based aCGH
      using amniocyte DNA demonstrated partial trisomy 16p and partial monosomy 22q
      [arr cgh 16p13.3p12.2 (CTD-3077J14->RP11-650D5)x3, 22q13.31q13.33 (RP1-111J24
      >CTD-3035C16)x1]. Oligonucleotide-based aCGH showed a 20.9-Mb duplication of
      distal 16p and an approximate 3.7-Mb deletion of distal 22q. Level II ultrasound
      revealed fetal ascites and ventriculomegaly. The pregnancy was terminated and a
      malformed male fetus was delivered with craniofacial dysmorphism and
      abnormalities of the digits. The fetal karyotype was
      46,XY,der(22)t(16;22)(p12.2;q13.31)pat. The paternal karyotype was
      46,XY,t(16;22)(p12.2;q13.31). CONCLUSION: Partial trisomy 16p can be associated
      with fetal ascites and ventriculomegaly in the second trimester. Prenatal
      sonographic detection of fetal ascites in association with ventriculomegaly
      should alert chromosomal abnormalities and prompt cytogenetic investigation,
      which may lead to the identification of an unexpected parental translocation
      involving chromosomal segments associated with cerebral and vascular
      abnormalities.

PMID- 21199756
TI  - Postpartum hemorrhage of genital tract origin.

PMID- 21199757
TI  - A complicated hematometra and fallopian tubal occlusion in uterine didelphys with
      unilateral cervical atresia.

PMID- 21199758
TI  - Laparoscopic removal of a migrated intrauterine contraceptive device with bladder
      penetration.

PMID- 21199759
TI  - A virgin diagnosed with foreign body granuloma: myth or fact?

PMID- 21199760
TI  - Urethral leiomyoma mimicking a caruncle.

PMID- 21199761
TI  - Brain and intramedullary spinal cord metastasis from squamous cell cervical
      carcinoma.

PMID- 21199762
TI  - Pelvic abscess after laparoscopic myomectomy with vaginal extraction.

PMID- 21199763
TI  - Vaginal leiomyoma presenting as dysfunctional uterine bleeding.

PMID- 21199764
TI  - Placental site trophoblastic tumor--a challenging, rare entity.

PMID- 21199765
TI  - Transabdominal ultrasound-guided intra-gestational sac single dose MTX injection
      in a tubal pregnancy.

PMID- 21199766
TI  - Partial trisomy 10q (10q25.1 ->qter) and partial monosomy 13q (13q34->qter)
      presenting with fetal pyelectasis: prenatal diagnosis and array comparative
      genomic hybridization characterization.

PMID- 21199767
TI  - Recurrent distal 16q duplication and terminal 22q deletion: prenatal diagnosis
      and genetic counseling.

PMID- 21199768
TI  - Preclinical research and drug development in humans. Preface.

PMID- 21199770
TI  - Therapeutic targets in Alzheimer's disease and related tauopathies.
AB  - Alzheimer's disease is a progressive neurodegenerative disease that is
      characterized histopathologically by the presence of plaques, mainly composed of
      Abeta amyloid and the tangles, mainly composed of hyperphosphorylated tau. To
      date, there is no treatment that can reverse the disease, and all the current
      therapeutics is directed to cope with the symptoms of the disease. Here we
      describe the efforts dedicated to attack the plaques and, in more detail, the
      process of neurofibrillary degeneration, linked to the presence of the
      hyperphosphorylated microtubule associated protein tau. We have identified the
      different putative targets for therapeutics and the current knowledge on them.

PMID- 21199771
TI  - Therapeutic targets for neuroprotection and/or enhancement of functional recovery
      following traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a significant public health concern. The number
      of injuries that occur each year, the cost of care, and the disabilities that can
      lower the victim's quality of life are all driving factors for the development of
      therapy. However, in spite of a wealth of promising preclinical results,
      clinicians are still lacking a therapy. The use of preclinical models of the
      primary mechanical trauma have greatly advanced our knowledge of the complex
      biochemical sequela that follow. This cascade of molecular, cellular, and
      systemwide changes involves plasticity in many different neurochemical systems,
      which represent putative targets for remediation or attenuation of neuronal
      injury. The purpose of this chapter is to highlight some of the promising
      molecular and cellular targets that have been identified and to provide an up-to
      date summary of the development of therapeutic compounds for those targets.

PMID- 21199772
TI  - Insulin, synaptic function, and opportunities for neuroprotection.
AB  - A steadily growing number of studies have begun to establish that the brain and
      insulin, while traditionally viewed as separate, do indeed have a relationship.
      The uptake of pancreatic insulin, along with neuronal biosynthesis, provides
      neural tissue with the hormone. As well, insulin acts upon a neuronal receptor
      that, although a close reflection of its peripheral counterpart, is characterized
      by unique structural and functional properties. One distinction is that the
      neural variant plays only a limited part in neuronal glucose transport. However,
      a number of other roles for neural insulin are gradually emerging; most
      significant among these is the modulation of ligand-gated ion channel (LGIC)
      trafficking. Notably, insulin has been shown to affect the tone of synaptic
      transmission by regulating cell-surface expression of inhibitory and excitatory
      receptors. The manner in which insulin regulates receptor movement may provide a
      cellular mechanism for insulin-mediated neuroprotection in the absence of
      hypoglycemia and stimulate the exploration of new therapeutic opportunities.

PMID- 21199774
TI  - Molecular signaling and translational significance of the corticotropin releasing
      factor system.
AB  - The corticotropin releasing factor (CRF) system coordinates a wide range of
      stress responses and has been implicated in the etiology of a number of clinical
      disorders. It is made up of a complex array of interactive peptides that interact
      with many other neurotransmitter and neuromodulatory systems. Dysregulation of
      CRF system signaling may be a common molecular pathway for the myriad "stress
      related" disorders. Understanding the signaling and circuitry affected by this
      system is essential to understanding these psychiatric disorders. The extremely
      wide range of behaviors and physiological processes mediated by this system and
      the complexity of its signaling make this a difficult task-especially to
      successfully target it for pharmacotherapy. In this review, we describe the
      molecular signaling of the CRF system and its interaction with other key
      neurotransmitter systems. Its role in a range of psychiatric disorders and
      potential as a target for therapeutic intervention will also be discussed.

PMID- 21199773
TI  - Molecular alterations in glioblastoma: potential targets for immunotherapy.
AB  - Glioblastoma is the most common and deadly brain tumor, possibly arising from
      genetic and epigenetic alterations in normal astroglial cells. Multiple
      cytogenetic, chromosomal, and genetic alterations have been identified in
      glioblastoma, with distinct expression of antigens (Ags) and biomarkers that may
      alter therapeutic potential of this aggressive cancer. Current therapy consists
      of surgical resection, followed by radiation therapy and chemotherapy. In spite
      of these treatments, the prognosis for glioblastoma patients is poor. Although
      recent studies have focused on the development of novel immunotherapeutics
      against glioblastoma, little is known about glioblastoma-specific immune
      responses. A better understanding of the molecular interactions among
      glioblastoma tumors, host immune cells, and the tumor microenvironment may give
      rise to novel integrated approaches for the simultaneous control of tumor escape
      pathways and the activation of antitumor immune responses. This review provides a
      detailed overview concerning genetic alterations in glioblastoma, their effects
      on Ag and biomarker expression, and the future design of chemoimmunotherapeutics
      against glioblastoma.

PMID- 21199769
TI  - Monoamine transporters: vulnerable and vital doorkeepers.
AB  - Transporters of dopamine, serotonin, and norepinephrine have been empirically
      used as medication targets for several mental illnesses in the last decades.
      These protein-targeted medications are effective only for subpopulations of
      patients with transporter-related brain disorders. Since the cDNA clonings in
      early 1990s, molecular studies of these transporters have revealed a wealth of
      information about the transporters' structure-activity relationship (SAR),
      neuropharmacology, cell biology, biochemistry, pharmacogenetics, and the diseases
      related to the human genes encoding these transporters among related regulators.
      Such new information creates a unique opportunity to develop transporter-specific
      medications based on SAR, mRNA, DNA, and perhaps transporter trafficking
      regulation for a number of highly relevant diseases including substance abuse,
      depression, schizophrenia, and Parkinson's disease.

PMID- 21199776
TI  - Brain nicotinic receptors as emerging targets for drug addiction: neurobiology to
      translational research.
AB  - Drug addiction, a chronic relapsing disorder, is a serious public health problem
      around the world. A growing body of preclinical and clinical evidence suggests
      that mammalian brain nicotinic acetylcholine receptors (nAChRs), the
      heterogeneous family of ion channels, play a pivotal role in drug addiction,
      including nicotine and alcohol dependence. As a result, there is an increasing
      interest in developing nAChR-based therapies for the treatment of addictive
      disorders. The current review summarizes the important preclinical and clinical
      data, demonstrating the ability of nAChR ligands to modulate nicotine and alcohol
      induced biobehavioral and neurochemical changes in laboratory animals and humans.
      Recent studies suggest that partial agonists and antagonists at nAChRs have
      therapeutic potential for the management of nicotine and alcohol dependence. The
      complexity of nAChRs and their regulation for the development of nAChR-based drug
      candidates as novel pharmacotherapy for other addictive disorders will also be
      discussed. Taken together, this review will provide new insights into nAChR-based
      compounds and offer innovative translational strategies for combating drug
      addictive disorders.

PMID- 21199777
TI  - Glutamatergic neuroplasticity in cocaine addiction.
AB  - Neuroadaptations among glutamatergic projections within the mesocorticolimbic
      circuits engaged by drugs of abuse have been described since the 1990s. There is
      now substantial evidence that drugs of abuse lead to long-term changes in
      glutamatergic signaling and encompass multiple levels of analysis. For example,
      cocaine induces changes in extracellular glutamate concentrations and in synaptic
      glutamatergic transmission. In addition, glutamate receptors are required for the
      expression of cocaine-related behaviors, and long-term changes have been reported
      in the expression of proteins at glutamatergic synapses, in glutamate-related
      redox regulation of neurons, and in glutamatergic synaptic and structural
      plasticity following chronic exposure to cocaine. In this chapter, we will
      describe the neurocircuitry involved, and will summarize evidence for adaptations
      in glutamatergic neuroplasticity as a mechanism for cocaine addiction. Finally,
      we will discuss progress in the development of glutamate-mediated
      pharmacotherapies for the treatment of cocaine dependence.

PMID- 21199775
TI  - Molecular targets of alcohol action: Translational research for pharmacotherapy
      development and screening.
AB  - Alcohol abuse and dependence are multifaceted disorders with neurobiological,
      psychological, and environmental components. Research on other complex
      neuropsychiatric diseases suggests that genetically influenced intermediate
      characteristics affect the risk for heavy alcohol consumption and its
      consequences. Diverse therapeutic interventions can be developed through
      identification of reliable biomarkers for this disorder and new pharmacological
      targets for its treatment. Advances in the fields of genomics and proteomics
      offer a number of possible targets for the development of new therapeutic
      approaches. This brain-focused review highlights studies identifying
      neurobiological systems associated with these targets and possible
      pharmacotherapies, summarizing evidence from clinically relevant animal and human
      studies, as well as sketching improvements and challenges facing the fields of
      proteomics and genomics. Concluding thoughts on using results from these
      profiling technologies for medication development are also presented.

PMID- 21199779
TI  - MicroRNAs in Drosophila development.
AB  - Micro-ribonucleic acids (miRNAs) are small (21-24 nucleotide), endogenously
      expressed, noncoding RNAs that have emerged as important posttranscriptional
      regulators of gene expression. MiRNAs have been identified and cloned from
      diverse eukaryotic organisms where they have been shown to control important
      physiological and developmental processes such as apoptosis, cell division, and
      differentiation. A high level of conservation of some miRNAs across phyla further
      emphasizes their importance as posttranscriptional regulators. Research in a
      variety of model systems has been instrumental in dissecting the biological
      functions of miRNAs. In this chapter, we discuss the current literature on the
      role of miRNAs as developmental regulators in Drosophila.

PMID- 21199780
TI  - New insights into the mechanism of development of Arabidopsis root hairs and
      trichomes.
AB  - Epidermis cell differentiation in Arabidopsis thaliana is a model system for
      understanding the mechanisms leading to the developmental end state of plant
      cells. Both root hairs and trichomes differentiate from epidermal cells and
      molecular genetic analyses using Arabidopsis mutants have demonstrated that the
      differentiation of root hairs and trichomes is regulated by similar molecular
      mechanisms. Molecular-genetic approaches have led to the identification of many
      genes that are involved in epidermal cell differentiation, most of which encode
      transcription factors that induce the expression of genes active in both root
      hair and trichome development. Control of cell growth after fate determination
      has also been studied using Arabidopsis mutants.

PMID- 21199778
TI  - Role of the serotonergic system in alcohol dependence: from animal models to
      clinics.
AB  - Alcohol dependence remains among the most common substance abuse problems
      worldwide, and compulsive alcohol consumption is a significant public health
      concern. Alcohol is an addictive drug that alters brain function through
      interactions with multiple neurotransmitter systems. These neurotransmitter
      systems mediate the reinforcing effects of alcohol. Specifically, the
      serotonergic system is important in mediating alcohol reward, preference,
      dependence, and craving. In this review chapter, we first discuss the serotonin
      system as it relates to alcoholism, and then outline interactions between this
      system and other neurotransmitter systems. We emphasize the serotonin transporter
      and its possible role in alcoholism, then present several serotonergic receptors
      and discuss their contribution to alcoholism, and finally assess the serotonin
      system as a target for pharmacotherapy, with an emphasis on current and potential
      treatments.

PMID- 21199782
TI  - Dynamic behavior of double-membrane-bounded organelles in plant cells.
AB  - In plant cells, different kinds of single- and double-membrane-bounded cell
      organelles exhibit dynamic changes in their morphology, motility, and
      distribution patterns. The dynamic behavior of organelles plays crucial roles
      intimately associated with plant development and/or adaptive responses to
      environmental fluctuations. Recent progress in techniques for the visualization
      of cell organelles and cytoskeletal components has provided useful systems to
      dissect these complex processes, and revealed a number of striking features of
      plant organelle dynamics. This chapter summarizes recent findings on dynamic
      behavior of nuclei, mitochondria, and plastids in plant cells, focusing on
      imaging analyses and regulatory proteins.

PMID- 21199784
TI  - Abl family of tyrosine kinases and microbial pathogenesis.
AB  - Abl nonreceptor tyrosine kinases are activated by multiple stimuli and regulate
      cytoskeletal reorganization, cell proliferation, survival, and stress responses.
      Several downstream pathways have direct impact on physiological processes,
      including development and maintenance of the nervous and immune systems and
      epithelial morphogenesis. Recent studies also indicated that numerous viral and
      bacterial pathogens highjack Abl signaling for different purposes. Abl kinases
      are activated to reorganize the host actin cytoskeleton and promote the direct
      tyrosine phosphorylation of viral surface proteins and injected bacterial type
      III and type-IV effector molecules. However, Abl kinases also play other roles in
      infectious processes of bacteria, viruses, and prions. These activities have
      crucial impact on microbial invasion and release from host cells, actin-based
      motility, pedestal formation, as well as cell-cell dissociation involved in
      epithelial barrier disruption and other responses. Thus, Abl kinases exhibit
      important functions in pathological signaling during microbial infections. Here,
      we discuss the different signaling pathways activated by pathogens and highlight
      possible therapeutic intervention strategies.

PMID- 21199786
TI  - Vascular biology of magnesium and its transporters in hypertension.
AB  - Magnesium may influence blood pressure by modulating vascular tone and structure
      through its effects on myriad biochemical reactions that control vascular
      contraction/dilation, growth/apoptosis, differentiation and inflammation.
      Magnesium acts as a calcium channel antagonist, it stimulates production of
      vasodilator prostacyclins and nitric oxide and it alters vascular responses to
      vasoconstrictor agents. Mammalian cells regulate Mg2+ concentration through
      special transport systems that have only recently been characterized. Magnesium
      efflux occurs via Na2+-dependent and Na2+-independent pathways. Mg2+ influx is
      controlled by recently cloned transporters including Mrs2p, SLC41A1, SLC41A2,
      ACDP2, MagT1, TRPM6 and TRPM7. Alterations in some of these systems may
      contribute to hypomagnesemia and intracellular Mg2+ deficiency in hypertension
      and other cardiovascular pathologies. In particular, increased Mg2+ efflux
      through dysregulation of the vascular Na+/Mg2+ exchanger and decreased Mg2+
      influx due to defective vascular and renal TRPM6/7 expression/activity may be
      important in altered vasomotor tone and consequently in blood pressure
      regulation. The present review discusses the role of Mg2+ in vascular biology and
      implications in hypertension and focuses on the putative transport systems that
      control magnesium homeostasis in the vascular system. Much research is still
      needed to clarify the exact mechanisms of cardiovascular Mg2+ regulation and the
      implications of aberrant cellular Mg2+ transport and altered cation status in the
      pathogenesis of hypertension and other cardiovascular diseases.

PMID- 21199787
TI  - Magnesium supplementation improves indicators of low magnesium status and
      inflammatory stress in adults older than 51 years with poor quality sleep.
AB  - Low magnesium status has been associated with numerous conditions characterized
      as having a chronic inflammatory stress component. Some animal findings indicate
      that a moderate magnesium deficiency, similar to which apparently commonly occurs
      in humans, may enhance inflammatory or oxidative stress induced by other factors,
      including disrupted sleep/sleep deprivation. Thus, an experiment was performed
      with 100 adults (22 males and 78 females) aged 59 +/- 8 years (range 51 to 85
      years) with poor sleep quality revealed by a Pittsburg Sleep Quality Index (PSQI)
      score higher than five. The participants were randomly assigned to two groups
      matched by gender, age, and overall PSQI score. After baseline assessment (week
      one) of body mass index (BMI), diet, blood and urine biochemical variables, and
      sleep quality, one group was given a 320 mg magnesium/day supplement as magnesium
      citrate and the other group a sodium citrate placebo for seven weeks. Final
      assessments were made five and seven weeks (which were combined for statistical
      analysis to reduce intra-individual variation) after supplement initiation for
      the 96 participants who completed the study as designed. Based on food diaries,
      58% of the participants were consuming less than the US. Estimated Average
      Requirement (EAR) for magnesium. Consuming less than the EAR was associated with
      a significantly higher BMI and plasma C-reactive protein (CRP) concentration.
      Only 40 participants had plasma CRP concentrations higher than 3.0 mg/L (an
      indication of chronic inflammatory stress). Overall PSQI scores improved (10.4 to
      6.6, p < 0.0001) and erythrocyte magnesium increased (4.75 to 5.05 pg/cell, p =
      0.01) regardless of magnesium or placebo supplementation. Magnesium vs placebo
      supplementation did not significantly affect serum magnesium when all
      participants were included in the analysis. When only the 37 participants with
      serum magnesium concentrations < 1.8 mg/dL (indication of deficient magnesium
      status) were analyzed, magnesium supplementation, but not the placebo, increased
      serum magnesium concentrations. Magnesium supplementation vs placebo decreased
      plasma CRP in participants with baseline values > 3.0 mg/L. The findings show
      that many individuals have a low magnesium status associated with increased
      chronic inflammatory stress that could be alleviated by increased magnesium
      intake. Because dietary magnesium intake did not change during the experimental
      period, another factor, possibly a placebo effect, improved sleep quality, which
      resulted in increased erythrocyte magnesium. This factor prevented the
      determination of whether magnesium deficiency contributes to poor sleep quality.
      The findings, however, suggest an association between magnesium status and sleep
      quality that needs further study to definitively determine whether a low
      magnesium status is a cause or an effect of poor sleep quality.

PMID- 21199783
TI  - The biology of the desmosome-like junction a versatile anchoring junction and
      signal transducer in the seminiferous epithelium.
AB  - Mammalian spermatogenesis, a complex process that involves the movement of
      developing germ cells across the seminiferous epithelium, entails extensive
      restructuring of Sertoli-Sertoli and Sertoli-germ cell junctions. Presently, it
      is not entirely clear how zygotene spermatocytes gain entry into the adluminal
      compartment of the seminiferous epithelium, which is sealed off from the systemic
      circulation by the Sertoli cell component of the blood-testis barrier, without
      compromising barrier integrity. To begin to address this question, it is critical
      that we first have a good understanding of the biology and the regulation of
      different types of Sertoli-Sertoli and Sertoli-germ cell junctions in the testis.
      Supported by recent studies in the field, we discuss how crosstalk between
      different types of junctions contributes to their restructuring during germ cell
      movement across the blood-testis barrier. We place special emphasis on the
      emerging role of desmosome-like junctions as signal transducers during germ cell
      movement across the seminiferous epithelium.

PMID- 21199788
TI  - Prescription for change: accessing medication in transitional Russia.
AB  - BACKGROUND Many Russians experienced difficulty in accessing prescription
      medication during the widespread health service disruption and rapid socio
      economic transition of the 1990s. This paper examines trends and determinants of
      access in Russia during this period.  METHODS Data were from nine rounds (1994
      2004) of the Russia Longitudinal Monitoring Survey, a 38-centre household panel
      survey. Trends were measured in failing to access prescribed medication for the
      following reasons: unobtainable from a pharmacy, unable to afford and 'other'
      reasons. Determinants of unaffordability were studied in 1994, 1998 and 2004,
      using cross-sectional, age-adjusted logistic regression, with further
      multivariate analyses of unaffordability and failure to access for 'other'
      reasons in 2004.  RESULTS After 1994, reporting of unavailability in pharmacies
      fell sharply from 25% to 4%. Meanwhile, unaffordability increased to 20% in 1998
      but declined to 9% by 2004. In 1994, significant determinants of unaffordability
      were unemployment and lacking health care insurance in men. By 2004, determinants
      included low income and material goods in both sexes; rented accommodation and
      low education in men; and chronic disease and disability-related retirement in
      women. Not obtaining medicines for 'other' reasons was more likely amongst
      frequent male drinkers, and low educated or cohabiting women. Regional and gender
      differences were widest in 1998, coinciding with the Russian financial crisis. 
      CONCLUSIONS Rapid improvements in drug availability in the late 1990s in Russia
      are a probable consequence of a more liberalized pharmaceutical sector and an
      improved pharmacy network, whilst later improvements in affordability may relate
      to expanded health care insurance coverage and economic recovery after the 1998
      crash. A significant minority still finds prescription costs problematic, notably
      poorer and sick individuals, with inequalities apparently widening. Non-monetary
      determinants of affordability indicate its partly subjective nature, however.
      Ongoing research into access is needed, due to recent national changes in
      prescription drug subsidies, and into doctor- and patient-related influences on
      access and prescribing for individual conditions.

PMID- 21199789
TI  - Postoperative lymphocyte percentage influences the long-term disease-free
      survival following a resection for colorectal carcinoma.
AB  - OBJECTIVE: The aim of this study is to examine the relationship between
      postoperative laboratory parameters of inflammation and the disease-free survival
      in patients undergoing resection for colorectal cancer. METHODS: Six hundred
      seventy-five consecutive patients who underwent an elective resection for primary
      colorectal cancer from October 1999 to March 2004 were included in this study. We
      examined the associations between cancer recurrence and white blood cell count,
      lymphocyte percentage, neutrophil percentage and C-reactive protein. RESULTS:
      Lymphocyte percentage on postoperative days 3 and 7 was significantly higher in
      patients without recurrence than in those with recurrence. Lymphocyte percentage
      on postoperative day 7 differed the most between the two groups. On postoperative
      day 7, Stage II patients with lymphocyte percentage >15% had significantly longer
      survival compared with the patients with lymphocyte percentage <= 15%. A
      multivariate analysis showed lymphocyte percentage <= 15% on postoperative day 7
      to be an independent prognostic factor, along with lymph node metastases and
      serosal invasion. Logistic regression analysis showed that blood loss (>250 ml)
      and postoperative complications were significant independent predictors of
      lymphocyte percentage <= 15% on postoperative day 7. CONCLUSIONS: Lymphocyte
      percentage <= 15% on postoperative day 7 is an independent prognostic factor for
      the patients undergoing a resection for colorectal cancer.

PMID- 21199781
TI  - Metastasis suppressor genes at the interface between the environment and tumor
      cell growth.
AB  - The molecular mechanisms and genetic programs required for cancer metastasis are
      sometimes overlapping, but components are clearly distinct from those promoting
      growth of a primary tumor. Every sequential, rate-limiting step in the sequence
      of events leading to metastasis requires coordinated expression of multiple
      genes, necessary signaling events, and favorable environmental conditions or the
      ability to escape negative selection pressures. Metastasis suppressors are
      molecules that inhibit the process of metastasis without preventing growth of the
      primary tumor. The cellular processes regulated by metastasis suppressors are
      diverse and function at every step in the metastatic cascade. As we gain
      knowledge into the molecular mechanisms of metastasis suppressors and cofactors
      with which they interact, we learn more about the process, including appreciation
      that some are potential targets for therapy of metastasis, the most lethal aspect
      of cancer. Until now, metastasis suppressors have been described largely by their
      function. With greater appreciation of their biochemical mechanisms of action,
      the importance of context is increasingly recognized especially since tumor cells
      exist in myriad microenvironments. In this chapter, we assemble the evidence that
      selected molecules are indeed suppressors of metastasis, collate the data
      defining the biochemical mechanisms of action, and glean insights regarding how
      metastasis suppressors regulate tumor cell communication to-from
      microenvironments.

PMID- 21199790
TI  - p53 status identifies two subgroups of triple-negative breast cancers with
      distinct biological features.
AB  - OBJECTIVE: Despite the clinical similarities triple-negative and basal-like
      breast cancer are not synonymous. Indeed, not all basal-like cancers are negative
      for estrogen receptor, progesterone receptor and HER2 expression while triple
      negative also encompasses other cancer types. P53 protein appears heterogeneously
      expressed in triple-negative breast cancers, suggesting that it may be associated
      with specific biological subgroups with a different outcome. METHODS: We
      comparatively analyzed p53 expression in triple-negative tumors from two
      independent breast cancer case series (633 cases from the University of Ferrara
      and 1076 cases from the University of Nottingham). RESULTS: In both case series,
      p53 protein expression was able to subdivide the triple-negative cases into two
      distinct subsets consistent with a different outcome. In fact, triple-negative
      patients with a p53 expressing tumor showed worse overall and event-free
      survival. CONCLUSIONS: The immunohistochemical evaluation of p53 expression may
      help in taming the currently stormy relationship between pathological (triple
      negative tumors) and biological (basal breast cancers) classifications and in
      selecting patient subgroups with different biological features providing a
      potentially powerful prognostic contribution in triple-negative breast cancers.

PMID- 21199792
TI  - Long intergenic noncoding RNAs: new links in cancer progression.
AB  - The process of cancer metastasis involves a series of sequential and complex
      steps. Here we give a perspective on recent results regarding noncoding
      transcription in cancer progression, focusing on the emerging role of long
      intergenic noncoding RNAs (lincRNAs). LincRNAs target chromatin modification
      complexes or RNA-binding proteins to alter gene expression programs. Similarly to
      miRNAs, lincRNAs exhibit distinct gene expression patterns in primary tumors and
      metastases. We discuss how lincRNAs can be used for cancer diagnosis and
      prognosis and serve as potential therapeutic targets.

PMID- 21199793
TI  - Fetal cell microchimerism and cancer: a nexus of reproduction, immunology, and
      tumor biology.
AB  - Fetal cell microchimerism (FCM) is the persistence of fetal cells in the maternal
      circulation and organs following pregnancy. Proposed hypotheses about the
      function of fetal cells in the pathogenesis of maternal cancer include promotion
      of tumorigenesis, protection by providing immunosurveillance, and participation
      in tissue repair. To date, studies of FCM and cancer have been primarily
      descriptive and quantitative. More research is needed to understand the cellular
      phenotype of the microchimeric cells in maternal tumors and whether they have a
      functional role. This research will require further study using a
      multidisciplinary approach, incorporating knowledge of the fetomaternal
      relationship, tumor biology, immunology, and clinical oncology.

PMID- 21199794
TI  - Lactate dehydrogenase B is critical for hyperactive mTOR-mediated tumorigenesis.
AB  - Mammalian target of rapamycin (mTOR) is a major downstream effector of the
      receptor tyrosine kinase (RTK)-phosphoinositide 3-kinase (PI3K)-v-akt murine
      thymoma viral oncogene homologue 1 (AKT) signaling pathway. Although this
      signaling network is frequently altered in cancer, the underlying mechanisms that
      cause tumorigenesis as a result of activated mTOR remain largely unknown. We
      report here that expression of lactate dehydrogenase B (LDHB), a critical
      enzymatic activator of glycolysis, was upregulated in an mTOR-dependent manner in
      TSC1(-/-), TSC2(-/-), PTEN(-/-), or activated AKT1-expressing mouse embryonic
      fibroblasts (MEF). LDHB gene expression was transactivated by signal transducer
      and activator of transcription 3 (STAT3), a key tumorigenic driver in many
      cancers, acting as a downstream mTOR effector in both mouse MEFs and human cancer
      cells. LDHB attenuation blunted the tumorigenic potential of oncogenic TSC2-null
      cells in nude mice. We concluded that LDHB is a downstream target of mTOR that is
      critical for oncogenic mTOR-mediated tumorigenesis. Our findings offer proof of
      concept for targeting LDHB as a therapeutic strategy in cancers driven by
      aberrant activation of the RTK-PI3K-AKT-mTOR signaling cascade.

PMID- 21199795
TI  - Glioblastoma recurrence after cediranib therapy in patients: lack of "rebound"
      revascularization as mode of escape.
AB  - Recurrent glioblastomas (rGBM) invariably relapse after initial response to anti
      VEGF therapy. There are 2 prevailing hypotheses on how these tumors escape
      antiangiogenic therapy: switch to VEGF-independent angiogenic pathways and vessel
      co-option. However, direct evidence in rGBM patients is lacking. Thus, we
      compared molecular, cellular, and vascular parameters in autopsy tissues from 5
      rGBM patients who had been treated with the pan-VEGF receptor tyrosine kinase
      inhibitor cediranib versus 7 patients who received no therapy or chemoradiation
      but no antiangiogenic agents. After cediranib treatment, endothelial
      proliferation and glomeruloid vessels were decreased, and vessel diameters and
      perimeters were reduced to levels comparable to the unaffected contralateral
      brain hemisphere. In addition, tumor endothelial cells expressed molecular
      markers specific to the blood-brain barrier, indicative of a lack of
      revascularization despite the discontinuation of therapy. Surprisingly, in
      cediranib-treated GBM, cellular density in the central area of the tumor was
      lower than in control cases and gradually decreased toward the infiltrating edge,
      indicative of a change in growth pattern of rGBMs after cediranib treatment,
      unlike that after chemoradiation. Finally, cediranib-treated GBMs showed high
      levels of PDGF-C (platelet-derived growth factor C) and c-Met expression and
      infiltration by myeloid cells, which may potentially contribute to resistance to
      anti-VEGF therapy. In summary, we show that rGBMs switch their growth pattern
      after anti-VEGF therapy--characterized by lower tumor cellularity in the central
      area, decreased pseudopalisading necrosis, and blood vessels with normal
      molecular expression and morphology--without a second wave of angiogenesis.

PMID- 21199796
TI  - Endothelial cell-specific deletion of transcription factor FoxM1 increases
      urethane-induced lung carcinogenesis.
AB  - Vascular endothelial cells provide essential support to the tumor
      microenvironment, but little is known about the transcriptional control of
      endothelial functions during tumorigenesis. Here we define a critical role for
      the Forkhead transcription factor FoxM1 in modulating the development of tumor
      associated endothelial cells. Pulmonary tumorigenesis induced by urethane
      administration was compared in mice genetically deleted for FoxM1 in endothelial
      cells (enFoxm1(-/-) mice). Notably, lung tumor number and size were increased in
      enFoxm1(-/-) mice. Increased tumorigenesis was associated with increased
      proliferation of tumor cells and increased expression of c-Myc and cyclin D1.
      Furthermore, perivascular infiltration by inflammatory cells was elevated and
      inflammatory cells in BAL fluid were increased. Expression of Flk-1 (vascular
      endothelial growth factor receptor 2) and FoxF1, known regulators of pulmonary
      inflammation, was decreased in enFoxm1(-/-) mice. siRNA-mediated knockdown of
      FoxM1 in endothelial cells reduced Flk-1 and FoxF1 expression, which was driven
      by direct transcriptional induction by FoxM1 as target genes. Endothelial
      specific deletion of FoxM1 in vivo or in vitro also decreased expression of Sfrp1
      (secreted frizzled-related protein 1), a known inhibitor of canonical Wnt
      signaling, in a manner that was associated with increased Wnt signaling. Taken
      together, our results suggest that endothelial-specific expression of FoxM1
      limits lung inflammation and canonical Wnt signaling in lung epithelial cells,
      thereby restricting lung tumorigenesis.

PMID- 21199797
TI  - Identification of new microRNAs in paired normal and tumor breast tissue suggests
      a dual role for the ERBB2/Her2 gene.
AB  - To comprehensively characterize microRNA (miRNA) expression in breast cancer, we
      performed the first extensive next-generation sequencing expression analysis of
      this disease. We sequenced small RNA from tumors with paired samples of normal
      and tumor-adjacent breast tissue. Our results indicate that tumor identity is
      achieved mainly by variation in the expression levels of a common set of miRNAs
      rather than by tissue-specific expression. We also report 361 new, well-supported
      miRNA precursors. Nearly two-thirds of these new genes were detected in other
      human tissues and 49% of the miRNAs were found associated with Ago2 in MCF7
      cells. Ten percent of the new miRNAs are located in regions with high-level
      genomic amplifications in breast cancer. A new miRNA is encoded within the
      ERBB2/Her2 gene and amplification of this gene leads to overexpression of the new
      miRNA, indicating that this potent oncogene and important clinical marker may
      have two different biological functions. In summary, our work substantially
      expands the number of known miRNAs and highlights the complexity of small RNA
      expression in breast cancer.

PMID- 21199798
TI  - Molecular pathobiology of human cervical high-grade lesions: paracrine STAT3
      activation in tumor-instructed myeloid cells drives local MMP-9 expression.
AB  - In many tumors, the switch from precancerous lesions to malignancy critically
      relies on expression of the matrix-metalloprotease MMP-9, which is predominantly
      provided by infiltrating inflammatory cells. Our study defines a novel molecular
      cascade, how human neoplastic cells instruct tumor-associated myeloid cells to
      produce MMP-9. In biopsies of human papillomavirus-associated precancerous
      cervical intraepithelial neoplasia (CIN III lesions), we show broad activation of
      the transcription factor STAT3 and coexpression of MMP-9 in perivascular
      inflammatory cells. For the first time, we establish a causative link between
      tumor-mediated paracrine STAT3 activation and MMP-9 production by human tumor
      instructed monocytes, whereas NF-kappaB activation is dispensable for this
      response. Our data provide evidence that STAT3 does not directly induce MMP-9 but
      first leads to a strong production of the monocyte chemoattractant protein-1
      (CCL2) in the nanogram range. In a second phase, autocrine stimulation of the
      CCR2 receptor in the tumor-instructed monocytes amplifies MMP-9 expression via
      intracellular Ca(2+) signaling. These findings elucidate a critical mechanism in
      the molecular pathobiology of cervical carcinogenesis at the switch to
      malignancy. Particularly in tumors, which are associated with infectious agents,
      STAT3-driven inflammation may be pivotal to promote carcinogenesis, while at the
      same time limit NF-kappaB-dependent immune responses and thus rejection of the
      infected preneoplastic cells. The molecular cascade defined in this study
      provides the basis for a rational design of future adjuvant therapies of cervical
      precancerous lesions.

PMID- 21199799
TI  - Dose-dependent effects of focal fractionated irradiation on secondary malignant
      neoplasms in Nf1 mutant mice.
AB  - Secondary malignant neoplasms (SMN) are increasingly common complications of
      cancer therapy that have proven difficult to model in mice. Clinical observations
      suggest that the development of SMN correlates with radiation dose; however, this
      relationship has not been investigated systematically. We developed a novel
      procedure for administering fractionated cranial irradiation (CI) and
      investigated the incidence and spectrum of cancer in control and heterozygous Nf1
      mutant mice irradiated to a moderate (15 Gy) or high dose (30 Gy). Heterozygous
      Nf1 inactivation cooperated with CI to induce solid tumors and myeloid
      malignancies, with mice developing many of the most common SMNs found in human
      patients. CI-induced malignancies segregated according to radiation dose as
      Nf1(+/-) mice developed predominately hematologic abnormalities after 15 Gy,
      whereas solid tumors predominated at 30 Gy, suggesting that radiation dose
      thresholds exist for hematologic and nonhematologic cancers. Genetic and
      biochemical studies revealed discrete patterns of somatic Nf1 and Trp53
      inactivation and we observed hyperactive Ras signaling in many radiation-induced
      solid tumors. This technique for administering focal fractionated irradiation
      will facilitate mechanistic and translational studies of SMNs.

PMID- 21199800
TI  - A randomized trial of dietary intervention for breast cancer prevention.
AB  - Epidemiologic data and animal experiments suggest that dietary fat may influence
      risk of breast cancer. To determine whether intervention with a low-fat, high
      carbohydrate diet would reduce breast cancer incidence in women at increased risk
      of the disease, we carried out a randomized controlled trial in Canada. We
      recruited 4,690 women with extensive mammographic density and randomized them to
      an intervention group or a comparison group. The intervention group received
      intensive dietary counseling to reduce fat intake to a target of 15% of calories
      and increase carbohydrate to 65% of calories. Dietary intakes were assessed
      throughout using food records. Subjects were followed for at least 7 years and
      for an average of 10 years. The main outcome was invasive breast cancer.
      Percentage of calories from fat in the intervention group decreased from 30% at
      baseline to 20% after randomization and remained 9% to 10% lower than the
      comparison group throughout. There were 118 invasive breast cancers in the
      intervention group and 102 in the comparison group [adjusted hazard ratio = 1.19
      (95% CI: 0.91-1.55)]. Analysis of food records showed that fat intake at baseline
      and after randomization was not associated with total breast cancer incidence.
      Greater weight and lower carbohydrate intake at baseline and after randomization
      were associated with an increased risk of estrogen receptor (ER)-positive breast
      cancer. Our findings suggest that a sustained reduction in dietary fat intake did
      not reduce risk of breast cancer in women with extensive mammographic density.
      Weight and carbohydrate intakes were associated with risk of ER-positive breast
      cancer.

PMID- 21199801
TI  - Carminomycin I is an apoptosis inducer that targets the Golgi complex in clear
      cell renal carcinoma cells.
AB  - Clear cell renal cell carcinoma (CCRCC) evolves due to mutations in the Von
      Hippel-Lindau (VHL) tumor suppressor gene. Although the loss of VHL enables
      survival and proliferation of CCRCC cells, it is also expected to introduce
      vulnerabilities that may be exploited for therapeutics discovery. To this end, we
      developed a high-throughput screen to identify small molecules derived from
      plants, microorganisms, and marine organisms to which CCRCC cells are sensitive.
      Screening over 8,000 compounds using this approach, we report here the
      identification of the microbially derived compound carminomycin I (CA) as an
      effective inhibitor of VHL-defective (VHL(-/-)) CCRCC cell proliferation. CA also
      induced apoptosis in CCRCC cells by a mechanism independent of p53 or hypoxia
      inducible factor 2. We found that P-glycoprotein (P-gp) sequestered CA within the
      Golgi complex. Interestingly, Golgi sequestration was critical for the
      antiproliferative effects of CA and P-gp inhibitors abrogated this activity.
      Furthermore, CA induced cleavage of the Golgi protein p115 and the translocation
      of its C-terminal fragment to the nucleus. Finally, examination of the activity
      of the VHL-interacting Golgi protein, endoplasmic reticulum-Golgi intermediate
      compartment, ERGIC-53 showed that VHL could mediate protection from CA in CCRCC
      cells. Our natural product-based screening approach has revealed the P-gp
      mediated localization of anticancer compounds within the Golgi in CCRCC cells as
      a potential strategy of targeting VHL-deficient CCRCC cells.

PMID- 21199802
TI  - Novel synthetic antagonists of canonical Wnt signaling inhibit colorectal cancer
      cell growth.
AB  - Canonical Wnt signaling is deregulated in several types of human cancer where it
      plays a central role in tumor cell growth and progression. Here we report the
      identification of 2 new small molecules that specifically inhibit canonical Wnt
      pathway at the level of the destruction complex. Specificity was verified in
      various cellular reporter systems, a Xenopus double-axis formation assay and a
      gene expression profile analysis. In human colorectal cancer (CRC) cells, the new
      compounds JW67 and JW74 rapidly reduced active beta-catenin with a subsequent
      downregulation of Wnt target genes, including AXIN2, SP5, and NKD1. Notably,
      AXIN2 protein levels were strongly increased after compound exposure. Long-term
      treatment with JW74 inhibited the growth of tumor cells in both a mouse xenograft
      model of CRC and in Apc(Min) mice (multiple intestinal neoplasia, Min). Our
      findings rationalize further preclinical and clinical evaluation of these new
      compounds as novel modalities for cancer treatment.

PMID- 21199803
TI  - Activation and involvement of Ral GTPases in colorectal cancer.
AB  - Current approaches to block KRAS oncogene function focus on inhibition of K-Ras
      downstream effector signaling. We evaluated the antitumor activity of selumetinib
      (AZD6244, ARRY-142886), a potent and selective MEK1/2 inhibitor, on a panel of
      colorectal carcinoma (CRC) cells and found no inhibition of KRAS mutant CRC cell
      anchorage-independent growth. Although AKT activity was elevated in KRAS mutant
      cells, and PI3K inhibition did impair the growth of MEK inhibitor-insensitive CRC
      cell lines, concurrent treatment with selumetinib did not provide additional
      antitumor activity. Therefore, we speculated that inhibition of the Ral guanine
      exchange factor (RalGEF) effector pathway may be a more effective approach for
      blocking CRC growth. RalGEFs are activators of the related RalA and RalB small
      GTPases and we found activation of both in CRC cell lines and patient tumors.
      Interfering RNA stable suppression of RalA expression reduced CRC tumor cell
      anchorage-independent growth, but surprisingly, stable suppression of RalB
      greatly enhanced soft agar colony size and formation frequency. Despite their
      opposing activities, both RalA and RalB regulation of anchorage-independent
      growth required interaction with RalBP1/RLIP76 and components of the exocyst
      complex. Interestingly, RalA interaction with the Exo84 but not Sec5 exocyst
      component was necessary for supporting anchorage-independent growth, whereas RalB
      interaction with Sec5 but not Exo84 was necessary for inhibition of anchorage
      independent growth. We suggest that anti-RalA-selective therapies may provide an
      effective approach for KRAS mutant CRC.

PMID- 21199804
TI  - MiR-26a inhibits cell growth and tumorigenesis of nasopharyngeal carcinoma
      through repression of EZH2.
AB  - Several microRNAs (miRNA) have been implicated in nasopharyngeal carcinoma (NPC),
      a highly invasive and metastatic cancer that is widely prevalent in southern
      China. In this study, we report that microRNA miR-26a is commonly downregulated
      in NPC specimens and NPC cell lines with important functional consequences.
      Ectopic expression of miR-26a dramatically suppressed cell proliferation and
      colony formation by inducing G(1)-phase cell-cycle arrest. We found that miR-26a
      strongly reduced the expression of EZH2 oncogene in NPC cells. Similar to the
      restoring miR-26 expression, EZH2 downregulation inhibited cell growth and cell
      cycle progression, whereas EZH2 overexpression rescued the suppressive effect of
      miR-26a. Mechanistic investigations revealed that miR-26a suppressed the
      expression of c-myc, the cyclin D3 and E2, and the cyclin-dependent kinase CDK4
      and CDK6 while enhancing the expression of CDK inhibitors p14(ARF) and p21(CIP1)
      in an EZH2-dependent manner. Interestingly, cyclin D2 was regulated by miR-26a
      but not by EZH2, revealing cyclin D2 as another direct yet mechanistically
      distinct target of miR-26a. In clinical specimens, EZH2 was widely overexpressed
      and its mRNA levels were inversely correlated with miR-26a expression. Taken
      together, our results indicate that miR-26a functions as a growth-suppressive
      miRNA in NPC, and that its suppressive effects are mediated chiefly by repressing
      EZH2 expression.

PMID- 21199805
TI  - Snail2 is an essential mediator of Twist1-induced epithelial mesenchymal
      transition and metastasis.
AB  - To metastasize, carcinoma cells must attenuate cell-cell adhesion to disseminate
      into distant organs. A group of transcription factors, including Twist1, Snail1,
      Snail2, ZEB1, and ZEB2, have been shown to induce epithelial mesenchymal
      transition (EMT), thus promoting tumor dissemination. However, it is unknown
      whether these transcription factors function independently or coordinately to
      activate the EMT program. Here we report that direct induction of Snail2 is
      essential for Twist1 to induce EMT. Snail2 knockdown completely blocks the
      ability of Twist1 to suppress E-cadherin transcription. Twist1 binds to an
      evolutionarily conserved E-box on the proximate Snail2 promoter to induce its
      transcription. Snail2 induction is essential for Twist1-induced cell invasion and
      distant metastasis in mice. In human breast tumors, the expression of Twist1 and
      Snail2 is highly correlated. Together, our results show that Twist1 needs to
      induce Snail2 to suppress the epithelial branch of the EMT program and that
      Twist1 and Snail2 act together to promote EMT and tumor metastasis.

PMID- 21199806
TI  - Higher miRNA tolerance in immortal Li-Fraumeni fibroblasts with abrogated
      interferon signaling pathway.
AB  - The IFN pathway is abrogated in fibroblasts from Li-Fraumeni syndrome (LFS)
      patients during spontaneous cellular immortalization, a necessary step in
      carcinogenesis. Microarray profiling of differentially expressed microRNAs
      (miRNA) revealed that most miRNAs were upregulated in IFN pathway-defective
      MDAH087-10 fibroblasts compared with MDAH087-N cells with relatively normal IFN
      signaling. Overexpression of Dicer, a critical enzyme in miRNA biogenesis,
      promoted cell growth and colony formation in MDAH087-10 cells. However, double
      stranded miRNA produced by Dicer enhanced the expression of IFN-stimulated genes
      in MDAH087-N cells resulting in significant cell death and reduced cell growth.
      Furthermore, manipulation of the IFN pathway in immortal LFS fibroblasts through
      transcription factor IRF7 reversed their response to Dicer overexpression due to
      changed IFN pathway activity. Dicer overexpressing MDAH087-N cells contained
      lower levels of miRNA than vector control, and conversely much higher miRNA
      expression was detected in Dicer-transfected MDAH087-10 cells. Therefore, cells
      with a defective IFN pathway have a higher miRNA tolerance than cells with normal
      IFN pathway. This work indicates for the first time that the IFN pathway as
      mediated through the transcription factor IRF7 must be disrupted to permit miRNA
      upregulation to occur in early carcinogenesis. The IFN pathway appears to provide
      a checkpoint for miRNA level tolerance and its abrogation leads to cellular
      immortalization.

PMID- 21199807
TI  - Plasminogen activator uPA is a direct transcriptional target of the JAG1-Notch
      receptor signaling pathway in breast cancer.
AB  - Aberrant activation of the Notch receptor signaling pathway and overexpression of
      the Notch ligand JAG1 are associated with poor outcome in breast cancer. The
      plasminogen activator system, which includes urokinase-type plasminogen activator
      (uPA), has been validated as a marker of recurrence, high metastasis risk and
      death in breast malignancy. By using microarray profiling of breast cancer cell
      lines that had undergone siRNA-mediated abrogation of Notch signaling we
      uncovered a link between activated Notch signaling and uPA expression. An
      association between elevated expression of the Notch ligand JAG1, uPA, and the
      basal-like breast cancer subtype was confirmed in breast cancer cell lines. The
      association between JAG1 and uPA expression persisted in a survey of primary
      carcinomas of the breast. We found that Notch knockdown reduced transcription of
      uPA and phenocopied uPA knockdown in breast cancer cells. Through mutational
      analysis we identified a CBF-1 binding site in the uPA promoter that is required
      for direct transcriptional regulation by Notch. These data suggest that JAG1
      induced Notch activation results in breast cancer progression through
      upregulation of the plasminogen activator system, directly linking these 2
      important pathways of poor prognosis.

PMID- 21199808
TI  - Fish oil exacerbates colitis in SMAD3 mice.

PMID- 21199809
TI  - Variations in women's help seeking in response to intimate partner violence:
      findings from a Canadian population-based study.
AB  - This study examined the role of sociodemographic factors and violence
      characteristics in influencing women's use of informal and formal supports in
      response to intimate partner violence (IPV) in a national survey of Canadian
      households. A subset of female respondents in the 1999 Canadian General Social
      Survey who experienced at least one incident of physical or sexual IPV by a male
      current or former intimate partner was used for this analysis. Findings suggest
      that although there are significant sociodemographic variations in women's help
      seeking, the largest independent predictor of women's use of supports is fear
      that one's life is in danger.

PMID- 21199810
TI  - Battered women's perceptions of civil and criminal court helpfulness: the role of
      court outcome and process.
AB  - Although most battered women seeking formal help have some contact with court,
      limited research exists on what they find helpful and harmful about these
      experiences. Using qualitative data from low-income, largely Black battered
      women, this study finds that issues related to court outcomes, such as case
      disposition and enforcement, are important to evaluations of helpfulness. More
      frequently mentioned, however, are court processes, including treatment by staff,
      process length, and public disclosure. Results highlight the importance of
      research and practice attending to issues beyond court outcomes, as well as the
      potential impact supportive treatment at court may have for victims' recovery.

PMID- 21199811
TI  - The role of adaptation in advocate burnout: a case of good soldiering.
AB  - Domestic violence and sexual assault advocates, unlike other social service
      workers, experience only moderate burnout. The present study extends burnout
      research, exploring simultaneous effects of job demands and adaptation factors as
      they relate to burnout in the advocacy population. The authors identify the good
      soldiering phenomenon in which advocates adapt to work that is worthwhile, but
      risky, demanding, and resource poor. Good soldiering is related to, but distinct
      from, a "calling" because it links to the position, not simply intrinsic
      motivation. The authors find that though job demands significantly increase
      burnout, advocates who identify with good soldiering experience significantly
      lower levels of burnout.

PMID- 21199812
TI  - Incapacitated sexual violence involving alcohol among college women: the impact
      of a brief drinking intervention.
AB  - This study assessed the impact of a motivational interviewing (MI) brief alcohol
      intervention and prior victimization on alcohol-involved sexual victimization
      experiences. First-year female college students (N = 229) were randomly assigned
      to an intervention condition: MI, MI with feedback (MIFB), feedback (FB), and
      assessment only (AO). Findings indicate reduced alcohol use for all conditions
      and violence for MIFB, with interactions for prior victimization. The mechanism
      of change for reduced victimization was not reductions in alcohol use and
      mechanisms for this effectiveness remain somewhat convoluted. Tailoring of brief
      interventions addressing alcohol use and sexual violence, particularly for women
      with prior victimization, is critical.

PMID- 21199813
TI  - Challenges in interpreting cytokine biomarkers in biobehavioral research: a
      breast cancer exemplar.
AB  - PURPOSE: This report extends the findings of a prior study comparing the level of
      plasma cytokines in women with breast cancer to those of women with a benign
      breast biopsy with the addition of a normal comparison group. The results of this
      three-group comparison are presented as background for discussing several
      methodologic challenges for biobehavioral research in inflammatory-based
      conditions. METHOD: This study used a descriptive, cross-sectional design to
      compare the levels of plasma cytokines in women with breast cancer, women with a
      benign breast biopsy, and a normal comparison group. The levels of 17 cytokines
      were measured using multiplex bead array assays (Bio-Plex(r)). Data analysis
      included a variety of descriptive and graphical techniques to illustrate between
      group differences in cytokine profiles. RESULTS: The levels of plasma cytokines
      in the sample of 35 women who had recently been diagnosed with breast cancer, 24
      women with a suspicious breast mass, who subsequently were found to have a benign
      breast biopsy, and 33 women in a normal comparison group present a background for
      discussing the implications of extreme between-group differences for
      biobehavioral nursing research. Both the levels of individual cytokines and their
      patterns were distinctly different in the three groups. CONCLUSION: The exemplar
      presented from the three-group comparison has implications for planning
      biobehavioral nursing research in patients with conditions characterized by
      inflammation.

PMID- 21199814
TI  - Hindlimb muscle atrophy occurs from peripheral nerve damage in a rat neuropathic
      pain model.
AB  - OBJECTIVE: The purpose of this study was to examine the effect of neuropathic
      pain produced by peripheral nerve damage on mass, myofibrillar protein content,
      and cross-sectional areas of Type I and II fibers of rat hindlimb muscles.
      METHOD: Adult male Sprague-Dawley rats were assigned to one of three groups: a
      pain group (n = 10) that underwent ligation and cut of the left L5 spinal nerve,
      a sham group (n = 10) that underwent a sham cut procedure, or a control group (n
      = 10) that underwent no procedures. The withdrawal threshold test was done to
      assess pain threshold on each of Days 1-7 and 14. Activity, body weight, and food
      intake were measured daily for 2 weeks. At 15 days, rats were anesthetized and
      the bilateral soleus, plantaris, and gastrocnemius muscles dissected. RESULTS: At
      15 days post-ligation, the pain group had significant decreases in total dietary
      intake, body weight, activity, and muscle weight as compared to sham and control
      animals. Muscle weight and cross-sectional area of Type II fiber of the
      ipsilateral soleus, plantaris, and gastrocnemius muscles decreased as did
      myofibrillar protein content of the ipsilateral plantaris and gastrocnemius
      muscles. Muscle weight of the contralateral gastrocnemius muscle decreased, as
      did myofibrillar protein content and cross-sectional area of Type II fiber of the
      contralateral plantaris muscle. CONCLUSION: Hindlimb muscle atrophy occurs in
      both ipsilateral and contralateral sides following induction of neuropathic pain
      by unilateral peripheral nerve damage. Muscle changes of the ipsilateral side are
      more pronounced than those of the contralateral side.

PMID- 21199815
TI  - ''Ringing in the ears'': narrative review of tinnitus and its impact.
AB  - About 10% of the population experiences tinnitus, a common and distressing
      symptom characterized by the perception of sound in the absence of external
      stimuli. There is, however, marked heterogeneity in etiology, perception, and
      extent of distress among those who experience tinnitus. Reactions to tinnitus
      vary from simple awareness to severe irritation; some people have difficulty in
      hearing because of the loudness of the noise. Severe tinnitus causes many, often
      psychological, symptoms (e.g., tension, frustration, impaired concentration,
      disrupted sleep). For some, tinnitus is temporary, for others it is longstanding.
      Although many people adjust successfully, others are disabled by tinnitus;
      approximately 5% experience persistent and severe symptoms affecting their
      lifestyle and significantly reducing their quality of life. Because tinnitus is
      poorly understood and no single therapeutic approach is effective for all
      patients, many patients are told that ''nothing can be done'' and they must
      ''learn to live with it.'' In spite of these challenges, there is remarkably
      little relevant nursing literature on tinnitus. This literature review was
      conducted to explore current knowledge of tinnitus, including prevalence, causes
      and diagnosis, and assessment. Its psychosocial effects and impact on individuals
      are considered. Implications for practice are discussed-demonstrating that
      understanding the full impact of the condition and identifying patients' needs
      are essential to effective care.

PMID- 21199816
TI  - Health, social and economical consequences of sleep-disordered breathing: a
      controlled national study.
AB  - BACKGROUND: The objective direct and indirect costs of sleep-disordered breathing
      (snoring, sleep apnoea (SA) and obesity hypoventilation syndrome (OHS)) and the
      treatment are incompletely described. METHODS: Using data from the Danish
      National Patient Registry (1998-2006), 12,045, 19,438 and 755 patients were
      identified with a diagnosis of snoring, SA and OHS, respectively. For every
      patient, four age-, sex- and socioeconomic-matched citizens were randomly
      selected (48,180, 77,752 and 3020, respectively) from the Danish Civil
      Registration System Statistics Direct costs were extracted from the Danish
      Ministry of Health, Danish Medicines Agency and National Health Security and
      indirect costs were based on data derived from the Coherent Social Statistics.
      RESULTS: Snoring, and especially SA and OHS, were associated with significantly
      higher rates of health-related contact, medication use, unemployment and
      accounted for increased socioeconomic costs (especially indirect costs). These
      effects increased with the severity of SA and patients with OHS had the lowest
      employment rates. The income level of patients with SA and OHS who were employed
      was lower than that of employed control subjects. The annual excess total direct
      and indirect costs for patients with snoring, SA and OHS were ?705, ?3860 and
      ?11,320, respectively. Patients with snoring, SA and OHS received an annual mean
      excess social transfer income of ?147, ?879 and ?3263, respectively. These
      socioeconomic consequences were present up to 8 years prior to the first
      diagnosis in patients with SA and OHS, and further increased with disease
      advancement. Treatment with continuous positive airway pressure (CPAP) reduced
      mortality in patients with SA but not in those with OHS within an observation
      period of 2 years. CONCLUSION: Sleep-disordered breathing has major socioeconomic
      consequences for the individual patient and for society. Although CPAP treatment
      reduces mortality, earlier disease detection could have a greater impact on
      disease complications.

PMID- 21199817
TI  - Lung function, airway remodelling and inflammation in symptomatic infants:
      outcome at 3 years.
AB  - BACKGROUND: Relationships between early deficits of lung function, infant airway
      pathology and outcome in symptomatic infants are unclear. A study was undertaken
      to determine the associations between early lung function, airway histology and
      inflammation in symptomatic infants with the continuance of respiratory symptoms,
      lung function and subsequent use of inhaled asthma medication at the age of 3
      years. METHODS: 53 children who underwent lung function measurements and
      bronchoscopy following referral to a specialist children's hospital for recurrent
      lower respiratory symptoms at a mean age of 1 year were followed up at 3 years of
      age. Assessments were made of respiratory symptoms during the previous year, lung
      function by oscillometry and atopy by skin prick testing. Individual data on the
      purchase of asthma medications were obtained from the Social Insurance
      Institution for the 12 months preceding the follow-up visit. RESULTS: 50 children
      (94%) were re-evaluated, of whom 40 had ongoing airway symptoms. 11/39 (28%) who
      underwent successful oscillometry had reduced lung function, 31/50 (62%) used
      inhaled corticosteroids (ICS) regularly and 12/50 (24%) used ICS intermittently.
      Abnormal lung function at infancy was associated with ongoing airway symptoms
      (p<0.001) and with the purchase of ICS (p=0.009) and beta agonists (p=0.002).
      Reticular basement membrane thickness in infancy and the numbers of mucosal mast
      cells, but not eosinophils, correlated significantly with the amount of ICS
      purchased at 3 years (p=0.003 and p=0.018, respectively). CONCLUSIONS: Reduced
      lung function, thickening of the reticular basement membrane and increased
      density of mucosal mast cells in infancy are associated with respiratory
      morbidity and treatment needs at age 3 years in this highly selected group of
      children.

PMID- 21199818
TI  - Sex-specific trends in lung cancer incidence and survival: a population study of
      40,118 cases.
AB  - BACKGROUND AND AIM: Lung cancer is increasingly affecting women. The aim of this
      study was to identify sex-specific trends in lung cancer incidence and survival.
      METHODS: Complete national data on 40,118 cases from the Cancer Registry of
      Norway sampled from 1988 to 2007 are presented, with incidence rates, 1- and 5
      year relative survival in 5 year intervals and multivariate HRs adjusted for
      covariates, each with 95% CIs. RESULTS: Lung cancer incidence increased by 64%,
      with an age-adjusted annual average increase of 4.9% in women and 1.4% in men in
      this period. Relative survival was lower in men than in women in all time
      periods, and men had an increased risk of dying within 5 years of diagnosis
      compared with women (HR 1.14, 95% CI 1.11 to 1.17), adjusted for covariates.
      Adenocarcinoma is now the most frequent histological group in men and women, yet
      the risk of dying was higher in men in all histological subtypes except squamous
      cell carcinoma. A higher proportion of women than men were diagnosed with
      localised disease, and the risk of dying was significantly higher in men among
      all stages, most apparent in localised disease (HR 1.25, 95% CI 1.18 to 1.33).
      CONCLUSION: The findings highlight important characteristics of the lung cancer
      epidemic; despite a rising incidence of female lung cancer cases, women are
      diagnosed with less advanced disease than men; when adjusted for covariates, men
      have an increased risk of excess death at 5 years compared with women,
      irrespective of stage, age, period of diagnosis and selected histological
      subgroups.

PMID- 21199819
TI  - The Alg5 ortholog Wollknauel is essential for correct epidermal differentiation
      during Drosophila late embryogenesis.
AB  - The formation of an extracellular matrix (ECM) presupposes an ordered delivery of
      its components to ensure its stereotypic architecture. The Drosophila cuticle is
      an ECM produced by the epidermis at its apical site and is characterized by a
      layered organization. To understand the mechanisms of cuticle assembly during
      development, we have investigated early aspects of protein N-glycosylation, i.e.
      the attachment of a dolichol-linked oligosaccharide to distinct Asn sites of a
      protein known to be essential for sorting in the secretory pathway. Mutations in
      the Drosophila alg5 gene wollknauel (wol) that codes for an enzyme initiating the
      glucosylation of the dolichol-linked oligosaccharide decrease, as expected,
      glucosylation and the amounts of N-glycosylated proteins such as the cuticle
      organizing factor Knickkopf, without affecting their correct localization. At the
      same time, the polarity determinants Crumbs and atypical protein kinase C
      accumulate at the apical plasma membrane in wol deficient embryos. In part, these
      perturbations may also be caused by the unfolded protein response, which is
      commonly triggered by ER stress and downsizes transcription and translation in
      general. In any case, they are associated with the loss of cuticle layering and
      aberrant apical plasma membrane organization suggesting that glucosylation,
      either directly or indirectly through controlling protein degradation, is
      important for the efficient and balanced deployment of the biochemical functions
      of secreted and membrane-associated proteins during epidermal differentiation.

PMID- 21199821
TI  - Polysialic acid is required for neuropilin-2a/b-mediated control of CCL21-driven
      chemotaxis of mature dendritic cells and for their migration in vivo.
AB  - Migration of mature dendritic cells (mDCs) to secondary lymphoid organs is
      required for the development of immunity. Recently, we reported that polysialic
      acid (PSA) and the transmembrane glycoprotein neuropilin-2 (NRP2) control mDC
      chemotaxis to CCL21 and that this process is dependent on the C-terminal basic
      region of the chemokine. Herein, we provide further insight into the molecular
      components controlling PSA regulated chemotaxis in mDCs. In the present study, we
      demonstrate that human mDCs express the NRP2 isoforms NRP2a and NRP2b, that both
      of them are susceptible to polysialylation and that polysialylation is required
      to specifically enhance chemotaxis toward CCL21 in mDCs. The results presented
      suggest that PSA attached to NRP2 isoforms acts as a binding module for the CCL21
      chemokine, thereby facilitating its presentation to the chemokine receptor CCR7.
      To investigate the relevance of polysialylation on mDC migration, a xenograft
      mouse model was used and the migration of human DCs to mouse lymph nodes
      analyzed. Here, we demonstrate that the depletion of PSA from mDCs results in a
      drastic reduction in the migration of the cells to draining popliteal lymph
      nodes. With this finding, we provide first evidence that PSA is a crucial factor
      for in vivo migration of mDCs to lymph nodes.

PMID- 21199820
TI  - The annotation of the asparagine N-linked glycosylation pathway in the Reactome
      database.
AB  - Asparagine N-linked glycosylation is one of the most important forms of protein
      post-translational modification in eukaryotes and is one of the first metabolic
      pathways described at a biochemical level. Here, we report a new annotation of
      this pathway for the Human species, published after passing a peer-review process
      in Reactome. The new annotation presented here offers a high level of detail and
      provides references and descriptions for each reaction, along with integration
      with GeneOntology and other databases. The open-source approach of Reactome
      toward annotation encourages feedback from its users, making it easier to keep
      the annotation of this pathway updated with future knowledge. Reactome's web
      interface allows easy navigation between steps involved in the pathway to compare
      it with other pathways and resources in other scientific databases and to export
      it to BioPax and SBML formats, making it accessible for computational studies.
      This new entry in Reactome expands and complements the annotations already
      published in databases for biological pathways and provides a common reference to
      researchers interested in studying this important pathway in the human species.
      Finally, we discuss the status of the annotation of this pathway and point out
      which steps are worth further investigation or need better experimental
      validation.

PMID- 21199822
TI  - Pre- and post-irradiation fading effect for LiF:Mg,Ti and LiF:Mg,Cu,P materials
      used in routine monitoring.
AB  - LiF is a well-known thermoluminescent (TL) material used in individual
      monitoring, and its fading characteristics have been studied for years. In the
      present study, the fading characteristics (for a period of 150 d) of various
      commercial LiF materials with different dopants have been evaluated. The
      materials used in the study are those used in routine procedures by the Personal
      Dosimetry Department of Greek Atomic Energy Commission and in particular,
      LiF:Mg,Ti (MTS-N, TL Poland), LiF:Mg,Cu,P (MCP-N, TL Poland), LiF:Mg,Cu,P (MCP
      Ns, thin active layer detector, TL Poland) and LiF:Mg,Cu,P (TLD100H, Harshaw).
      The study showed that there is a sensitivity loss in signal of up to 20 % for the
      MTS-N material for a 150-d period in the pre-irradiation fading phase. The MCP-N
      has a stable behaviour in the pre-irradiation fading phase, but this also depends
      on the readout system. As far as the post-irradiation fading effect is concerned,
      a decrease of up to 20 % for the MTS-N material is observed for the same time
      period. On the other hand, the LiF:Mg,Cu,P material presents a stable behaviour
      within +/- 5 %. These results show that the fading effect is different for each
      material and should be taken into account when estimating doses from dosemeters
      that are in use for >2 months.

PMID- 21199823
TI  - Automation of film densitometry for application in personal monitoring.
AB  - In this research work, a semi-automatic densitometry system has been developed
      for large-scale monitoring services by use of film badge dosemeters. The system
      consists of a charge-coupled device (CCD)-based scanner that can scan optical
      densities (ODs) up to 4.2, a computer vision algorithm to improve the quality of
      digitised films and an analyser program to calculate the necessary information,
      e.g. the mean OD of region of interest and radiation doses. For calibration of
      the system, two reference films were used. The Microtek scanner International
      Color Consortium (ICC) profiler is applied for determining the colour attributes
      of the scanner accurately and a reference of the density step tablet,
      Bundesanstalt fur Materialforschung und-prufung (BAM) is used for calibrating the
      automatic conversion of gray-level values to OD values in the range of 0.2-4.0
      OD. The system contributes to achieve more objectives and reliable results. So by
      applying this system, we can digitise a set of 20 films at once and calculate
      their relative doses less than about 4 min, and meanwhile it causes to avoid
      disadvantages of manual process and to enhance the accuracy of dosimetry.

PMID- 21199824
TI  - The risks to healthy tissues from the use of existing and emerging techniques for
      radiation therapy.
AB  - As radical radiotherapy treatments become more effective, more and more cancer
      patients are becoming cured of their disease and surviving for decades. Damage to
      exposed healthy tissues that becomes manifest in the medium-to-long-term is
      becoming a more significant factor in the choice of individual treatment plans
      and treatment modality. However, currently there are no reliable objective
      methods for predicting in an individual patient the occurrence of normal tissue
      complications, or second cancers caused by radiation. This is especially needed
      as new competing techniques and modalities become available, such as IMRT,
      protons, carbon ions, etc., all advancing the ability to focus the radiation dose
      on the target while sparing normal tissue. ALLEGRO is a Euratom-funded project
      that is currently investigating the current state of knowledge, and attempting to
      define the priority research areas. Preliminary considerations of the problems to
      be solved and research priorities are presented.

PMID- 21199825
TI  - Microdosemeter instrument (MIDN) for assessing risk in space.
AB  - Radiation in space generally produces higher dose rates than that on the Earth's
      surface, and contributions from primary galactic and solar events increase with
      altitude within the magnetosphere. Presently, no personnel monitor is available
      to astronauts for real-time monitoring of dose, radiation quality and regulatory
      risk. This group is developing a prototypic instrument for use in an unknown,
      time-varying radiation field. This microdosemeter-dosemeter nucleon instrument is
      for use in a spacesuit, spacecraft, remote rover and other applications. It
      provides absorbed dose, dose rate and dose equivalent in real time so that action
      can be taken to reduce exposure. Such a system has applications in health
      physics, anti-terrorism and radiation-hardening of electronics as well. The space
      system is described and results of ground-based studies are presented and
      compared with predictions of transport codes. An early prototype in 2007 was
      successfully launched, the only solid-state microdosemeter to have flown in
      space.

PMID- 21199826
TI  - 3D visualisation of the stochastic patterns of the radial dose in nano-volumes by
      a Monte Carlo simulation of HZE ion track structure.
AB  - The description of energy deposition by high charge and energy (HZE) nuclei is of
      importance for space radiation risk assessment and due to their use in
      hadrontherapy. Such ions deposit a large fraction of their energy within the so
      called core of the track and a smaller proportion in the penumbra (or track
      periphery). We study the stochastic patterns of the radial dependence of energy
      deposition using Monte Carlo track structure codes RITRACKS and RETRACKS, that
      were used to simulate HZE tracks and calculate energy deposition in voxels of 40
      nm. The simulation of a (56)Fe(26+) ion of 1 GeV u(-1) revealed zones of high
      energy deposition which maybe found as far as a few millimetres away from the
      track core in some simulations. The calculation also showed that ~43 % of the
      energy was deposited in the penumbra. These 3D stochastic simulations combined
      with a visualisation interface are a powerful tool for biophysicists which may be
      used to study radiation-induced biological effects such as double strand breaks
      and oxidative damage and the subsequent cellular and tissue damage processing and
      signalling.

PMID- 21199827
TI  - Linear vs. function-based dose algorithm designs.
AB  - The performance requirements prescribed in IEC 62387-1, 2007 recommend linear,
      additive algorithms for external dosimetry [IEC. Radiation protection
      instrumentation--passive integrating dosimetry systems for environmental and
      personal monitoring--Part 1: General characteristics and performance
      requirements. IEC 62387-1 (2007)]. Neither of the two current standards for
      performance of external dosimetry in the USA address the additivity of dose
      results [American National Standards Institute, Inc. American National Standard
      for dosimetry personnel dosimetry performance criteria for testing. ANSI/HPS
      N13.11 (2009); Department of Energy. Department of Energy Standard for the
      performance testing of personnel dosimetry systems. DOE/EH-0027 (1986)]. While
      there are significant merits to adopting a purely linear solution to estimating
      doses from multi-element external dosemeters, differences in the standards result
      in technical as well as perception challenges in designing a single algorithm
      approach that will satisfy both IEC and USA external dosimetry performance
      requirements. The dosimetry performance testing standards in the USA do not
      incorporate type testing, but rely on biennial performance tests to demonstrate
      proficiency in a wide range of pure and mixed fields. The test results are used
      exclusively to judge the system proficiency, with no specific requirements on the
      algorithm design. Technical challenges include mixed beta/photon fields with a
      beta dose as low as 0.30 mSv mixed with 0.05 mSv of low-energy photons.
      Perception-based challenges, resulting from over 20 y of experience with this
      type of performance testing in the USA, include the common belief that the
      overall quality of the dosemeter performance can be judged from performance to
      pure fields. This paper presents synthetic testing results from currently
      accredited function-based algorithms and new developed purely linear algorithms.
      A comparison of the performance data highlights the benefits of each approach and
      demonstrates that, at least for some dosemeter designs, it is possible for a
      single purely linear algorithm to satisfy both US and IEC performance
      requirements.

PMID- 21199828
TI  - In vivo dosimetry with diodes in a radiotherapy department in Pakistan.
AB  - The International Commission of Radiological Units (ICRU) sets a tolerance of +/
      5 % on dose delivery, with more recent data limiting the overall tolerances to +/
      3 %. One of the best methods for accurate dose delivery and quality check is in
      vivo dosimetry, while radiotherapy is performed. The present study was carried
      out to test the applicability of diodes for performing in vivo entrance dose
      measurements in external photon beam radiotherapy for pelvic tumours and its
      implementation as quality assurance tool in radiotherapy. During November 2007 to
      December 2009, in 300 patients who received pelvic radiotherapy on a multileaf
      collimator-assisted linear accelerator, the central axis dose was measured by in
      vivo dosimetry by p-Si diodes. Entrance dose measurements were taken by diodes
      and were compared with the prescribed dose. Totally 1000 calculations were
      performed. The mean and standard deviation between measured and prescribed dose
      was 1.26 +/- 2.8 %. In 938 measurements (93.8 %), the deviation was <5 % (1.36 +/
      2.9%); in 62 measurements (6.2 %) the mean deviation was >5 % (5.51 +/- 2.3 %).
      Larger variations were seen in lateral and oblique fields more than
      anteroposterior fields. For larger deviations, patients and diode positional
      errors were found to be the common factors alone or in combination with other
      factors. After additional corrections, repeated measurements were achieved within
      tolerance levels. This study showed that diode-detector-based in vivo dosimetry
      was simple, cost-effective, provides quick results and can serve as a useful
      quality assurance tool in radiotherapy. The data acquired in the present study
      can be used for evaluating output calibration of therapy machine, precision of
      calculations, effectiveness of treatment plan and patient setup.

PMID- 21199829
TI  - Effect of radiation-induced charge accumulation on build-up cap on the signal
      current from an ionisation chamber.
AB  - The signal current from a thimble ionisation chamber with a build-up cap made of
      an insulator decreases by about 0.41 % after being irradiated for 17 h at an air
      kerma rate of 41 Gy h(-1) by a collimated (60)Co gamma-ray beam in air. In
      contrast, the signal current remains constant when the thimble ionisation chamber
      is irradiated in a water phantom. During irradiation, positive charge is
      considered to accumulate near the outer surface of the build-up cap where
      electron equilibrium is not achieved. Secondary electrons travelling in the build
      up cap and the chamber wall toward the ionisation volume are decelerated by the
      electric field generated by the positive charge. Consequently, the signal current
      decreases with increasing charge accumulation because some secondary electrons
      are prevented from entering the ionisation volume. In the water phantom, electron
      equilibrium is established in and around the ionisation chamber and charge does
      not accumulate. To confirm this hypothesis, the signal current was measured for
      an ionisation chamber in air with a build-up cap wrapped with Al foil and covered
      with PMMA tubes. Electron equilibrium was established over the build-up cap
      because the tubes were thicker than the secondary electron range. The signal
      current decreased with increasing positive voltage applied to the Al foil. It was
      estimated from the results that positive charges equivalent to a voltage of over
      6 kV applied to the Al foil accumulated during irradiation. The signal current
      was also measured for an ionisation chamber with a metal build-up cap and for an
      ionisation chamber with a wall and build-up cap made of conductive plastic.

PMID- 21199830
TI  - Microdosimetric evaluation of the neutron field for BNCT at Kyoto University
      reactor by using the PHITS code.
AB  - In this study, microdosimetric energy distributions of secondary charged
      particles from the (10)B(n,alpha)(7)Li reaction in boron-neutron capture therapy
      (BNCT) field were calculated using the Particle and Heavy Ion Transport code
      System (PHITS). The PHITS simulation was performed to reproduce the geometrical
      set-up of an experiment that measured the microdosimetric energy distributions at
      the Kyoto University Reactor where two types of tissue-equivalent proportional
      counters were used, one with A-150 wall alone and another with a 50-ppm-boron
      loaded A-150 wall. It was found that the PHITS code is a useful tool for the
      simulation of the energy deposited in tissue in BNCT based on the comparisons
      with experimental results.

PMID- 21199831
TI  - Hyperuricaemia, chronic kidney disease, and outcomes in heart failure: potential
      mechanistic insights from epidemiological data.
AB  - AIM: To determine if the association between hyperuricaemia and poor outcomes in
      heart failure (HF) varies by chronic kidney disease (CKD). METHODS AND RESULTS:
      Of the 2645 systolic HF patients in the Beta-Blocker Evaluation of Survival Trial
      with data on baseline serum uric acid, 1422 had hyperuricaemia (uric acid >=6
      mg/dL for women and >=8 mg/dL for men). Propensity scores for hyperuricaemia,
      estimated for each patient, were used to assemble a matched cohort of 630 pairs
      of patients with and without hyperuricaemia who were balanced on 75 baseline
      characteristics. Associations of hyperuricaemia with outcomes during 25 months of
      median follow-up were examined in all patients and in those with and without CKD
      (estimated glomerular filtration rate of <60 mL/min/1.73 m(2)). Hyperuricaemia
      associated hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause
      mortality and HF hospitalization were 1.44 (1.12-1.85, P = 0.005) and 1.27 (1.02
      1.58, P = 0.031), respectively. Hazard ratios (95% CIs) for all-cause mortality
      among those with and without CKD were 0.96 (0.70-1.31, P = 0.792) and 1.40 (1.08
      1.82, P = 0.011), respectively (P for interaction, 0.071), and those for HF
      hospitalization among those with and without CKD were 0.99 (0.74-1.33, P = 0.942)
      and 1.49 (1.19-1.86, P = 0.001), respectively (P for interaction, 0.033).
      CONCLUSION: Hyperuricaemia has a significant association with poor outcomes in HF
      patients without CKD but not in those with CKD, suggesting that hyperuricaemia
      may predict poor outcomes when it is primarily a marker of increased xanthine
      oxidase activity, but not when it is primarily due to impaired renal excretion of
      uric acid.

PMID- 21199832
TI  - Flagellin administration protects gut mucosal tissue from irradiation-induced
      apoptosis via MKP-7 activity.
AB  - BACKGROUND AND AIMS: Radiotherapy for neoplastic disease is associated with
      significant adverse enteric effects associated with excessive cell death.
      Ionising radiation induces cell death by a mechanism that is dependent on JNK (c
      jun N-terminal kinase) pathway signalling. Additionally, it is known that cells
      exposed to extracellular bacterial products such as flagellin, pleiotropically
      activate a number of innate immune pathways, including that of JNK. The JNK
      pathway controls its own activity by inducing the transcription of mitogen
      activated protein kinase phosphatase-7 (MKP-7) which directly targets
      phosphorylated JNK, thus functioning as a negative feedback loop. Previously, it
      has been shown that flagellin limits ionising radiation-induced mortality in
      mice, but the cellular mechanism of protection remained unknown. METHODS: Wild
      type C57BL/6 or tlr5(-/-) C57BL/6 were injected with flagellin 2 h before
      exposure to irradiation, and their intestines were examined for apoptosis.
      Candidate proteins mediating cytoprotection from irradiation were identified by
      expression profiling. One of these candidates, MKP-7, was cloned and packaged
      into adenovirus particles, used to infect cultured cells, and examined for the
      extent to which its activity reduced cellular apoptosis by flow cytometry or
      immunoblot analysis. RESULTS: Flagellin pretreatment protected mice from
      radiation-induced intestinal mucosal injury and apoptosis via a Toll-like
      receptor 5 (TLR5)-dependent mechanism. Expression profiling of flagellin-treated
      mice showed upregulation of MKP-7, an inducible repressor of the JNK pathway. MKP
      7 expression reached a maximum at 2 h after flagellin treatment, coinciding with
      suppression of phosphorylated JNK and JNK pathway inhibition. Furthermore,
      constitutive MKP-7 expression protected cultured cells from radiation-induced
      apoptosis. CONCLUSIONS: Flagellin is a promising adjuvant for suppressing
      ionising radiation-induced injury. MKP-7 activity exhibits cytoprotective
      effects, and is thus a candidate cellular molecule for limiting the damaging
      effect of radiotherapy on the gastreointestinal system.

PMID- 21199833
TI  - Short- and long-term treatment of dilutional hyponatraemia with satavaptan, a
      selective arginine vasopressin V2-receptor antagonist: the DILIPO study.
AB  - AIMS: Arginine vasopressin (AVP) V(2) receptor antagonism is a new approach to
      the management of hyponatraemia in congestive heart failure (CHF). The aim of
      this study was to investigate the efficacy and safety of satavaptan, an oral AVP
      V(2)-receptor antagonist, in patients with dilutional hyponatraemia. METHODS AND
      RESULTS: A total of 118 patients (90 with CHF) with dilutional hyponatraemia
      (serum sodium 115-132 mmol/L) were randomized to double-blind treatment with
      placebo or to 25 or 50 mg/day of satavaptan for 4 days, followed by non
      comparative open-label satavaptan therapy for up to 343 days. The response rate
      (sodium >= 135 mmol/L and/or an increase in >= 5 mmol/L above baseline) was
      significantly higher with satavaptan 50 mg than with placebo (61.0 vs. 26.8%; P=
      0.0035), with a trend towards significance with satavaptan 25 mg (48.6%, P=
      0.0599). Median times to response were 3.30 and 2.79 days with satavaptan 25 and
      50 mg/day, respectively, both shorter than placebo (>4 days; P= 0.0278 and P=
      0.0004, respectively). Satavaptan therapy was effective in CHF patients, with
      response rates higher with both satavaptan 25 mg/day (53.6%) and 50 mg/day
      (57.1%) than with placebo (23.5%; P= 0.019 and P= 0.009, respectively). Sodium
      responses were maintained during open-label therapy after a temporary study drug
      discontinuation period. Higher rates of adverse events occurred with the 50
      mg/day dose, including rapid correction of hyponatraemia. CONCLUSIONS: In
      patients with dilutional hyponatraemia, V(2) receptor antagonism with satavaptan
      was effective in increasing serum sodium concentrations. The long-term open-label
      treatment results demonstrate sustained efficacy of satavaptan in maintaining
      normal sodium levels. Trial Registration clinicaltrials.gov Identifier:
      NCT00274326.

PMID- 21199835
TI  - Multi-trait interactions, not phylogeny, fine-tune leaf size reduction with
      increasing altitude.
AB  - BACKGROUND AND AIMS: Despite long-held interest, knowledge on why leaf size
      varies widely among species is still incomplete. This study was conducted to
      assess whether abiotic factors, phylogenetic histories and multi-trait
      interactions act together to shape leaf size. METHODS: Fifty-seven pairs of
      altitudinal vicariant species were selected in northern Spain, and leaf area and
      a number of functionally related leaf, shoot and whole plant traits were measured
      for each pair. Structural equation modelling helped unravel trait interactions
      affecting leaf size, and Mantel tests weighed the relative relevance of
      phylogeny, environment and trait interactions to explain leaf size reduction with
      altitude. KEY RESULTS: Leaves of highland vicariants were generally smaller than
      those of lowlands. However, the extent of leaf size reduction with increasing
      altitude was widely variable among genera: from approx. 700 cm(2) reduction (96 %
      in Polystichum) to approx. 30 cm(2) increase (37 % in Sorbus). This was partially
      explained by shifts in leaf, shoot and whole plant traits (35-64 % of explained
      variance, depending on models), with size/number trade-offs more influential than
      shifts in leaf form and leaf economics. Shifts in traits were more important than
      phylogenetic distances or site-specific environmental variation in explaining the
      degree of leaf size reduction with altitude. CONCLUSIONS: Ecological filters,
      constraints due to phylogenetic history (albeit modest in the study system), and
      phenotypic integration contribute jointly to shape single-trait evolution. Here,
      it was found that phenotypic change was far more important than shared ancestry
      to explain leaf size differences of closely related species segregated along
      altitudes.

PMID- 21199834
TI  - Elucidating the functional role of endoreduplication in tomato fruit development.
AB  - BACKGROUND: Endoreduplication is the major source of endopolyploidy in higher
      plants. The process of endoreduplication results from the ability of cells to
      modify their classical cell cycle into a partial cell cycle where DNA synthesis
      occurs independently from mitosis. Despite the ubiquitous occurrence of the
      phenomenon in eukaryotic cells, the physiological meaning of endoreduplication
      remains vague, although several roles during plant development have been
      proposed, mostly related to cell differentiation and cell size determination.
      SCOPE: Here recent advances in the knowledge of endoreduplication and fruit
      organogenesis are reviewed, focusing on tomato (Solanum lycopersicum) as a model,
      and the functional analyses of endoreduplication-associated regulatory genes in
      tomato fruit are described. CONCLUSIONS: The cyclin-dependent kinase inhibitory
      kinase WEE1 and the anaphase promoting complex activator CCS52A both participate
      in the control of cell size and the endoreduplication process driving cell
      expansion during early fruit development in tomato. Moreover the fruit-specific
      functional analysis of the tomato CDK inhibitor KRP1 reveals that cell size and
      fruit size determination can be uncoupled from DNA ploidy levels, indicating that
      endoreduplication acts rather as a limiting factor for cell growth. The overall
      functional data contribute to unravelling the physiological role of
      endoreduplication in growth induction of fleshy fruits.

PMID- 21199836
TI  - Evolutionary accounts of human behavioural diversity.
AB  - Human beings persist in an extraordinary range of ecological settings, in the
      process exhibiting enormous behavioural diversity, both within and between
      populations. People vary in their social, mating and parental behaviour and have
      diverse and elaborate beliefs, traditions, norms and institutions. The aim of
      this theme issue is to ask whether, and how, evolutionary theory can help us to
      understand this diversity. In this introductory article, we provide a background
      to the debate surrounding how best to understand behavioural diversity using
      evolutionary models of human behaviour. In particular, we examine how diversity
      has been viewed by the main subdisciplines within the human evolutionary
      behavioural sciences, focusing in particular on the human behavioural ecology,
      evolutionary psychology and cultural evolution approaches. In addition to
      differences in focus and methodology, these subdisciplines have traditionally
      varied in the emphasis placed on human universals, ecological factors and
      socially learned behaviour, and on how they have addressed the issue of genetic
      variation. We reaffirm that evolutionary theory provides an essential framework
      for understanding behavioural diversity within and between human populations, but
      argue that greater integration between the subfields is critical to developing a
      satisfactory understanding of diversity.

PMID- 21199837
TI  - Endless forms: human behavioural diversity and evolved universals.
AB  - Human populations have extraordinary capabilities for generating behavioural
      diversity without corresponding genetic diversity or change. These capabilities
      and their consequences can be grouped into three categories: strategic (or
      cognitive), ecological and cultural-evolutionary. Strategic aspects include: (i)
      a propensity to employ complex conditional strategies, some certainly genetically
      evolved but others owing to directed invention or to cultural evolution; (ii)
      situations in which fitness payoffs (or utilities) are frequency-dependent, so
      that there is no one best strategy; and (iii) the prevalence of multiple
      equilibria, with history or minor variations in starting conditions (path
      dependence) playing a crucial role. Ecological aspects refer to the fact that
      social behaviour and cultural institutions evolve in diverse niches, producing
      various adaptive radiations and local adaptations. Although environmental change
      can drive behavioural change, in humans, it is common for behavioural change
      (especially technological innovation) to drive environmental change (i.e. niche
      construction). Evolutionary aspects refer to the fact that human capacities for
      innovation and cultural transmission lead to diversification and cumulative
      cultural evolution; critical here is institutional design, in which relatively
      small shifts in incentive structure can produce very different aggregate
      outcomes. In effect, institutional design can reshape strategic games, bringing
      us full circle.

PMID- 21199838
TI  - Parental investment and the optimization of human family size.
AB  - Human reproductive behaviour is marked by exceptional variation at the population
      and individual level. Human behavioural ecologists propose adaptive hypotheses to
      explain this variation as shifting phenotypic optima in relation to local
      socioecological niches. Here we review evidence that variation in fertility
      (offspring number), in both traditional and modern industrialized populations,
      represents optimization of the life-history trade-off between reproductive rate
      and parental investment. While a reliance on correlational methods suggests the
      true costs of sibling resource competition are often poorly estimated, a range of
      anthropological and demographic studies confirm that parents balance family size
      against offspring success. Evidence of optimization is less forthcoming. Declines
      in fertility associated with modernization are particularly difficult to
      reconcile with adaptive models, because fertility limitation fails to enhance
      offspring reproductive success. Yet, considering alternative measures, we show
      that modern low fertility confers many advantages on offspring, which are
      probably transmitted to future generations. Evidence from populations that have
      undergone or initiated demographic transition indicate that these rewards to
      fertility limitation fall selectively on relatively wealthy individuals. The
      adaptive significance of modern reproductive behaviour remains difficult to
      evaluate, but may be best understood in response to rising investment costs of
      rearing socially and economically competitive offspring.

PMID- 21199839
TI  - Understanding the nature of wealth and its effects on human fitness.
AB  - Studying fitness consequences of variable behavioural, physiological and
      cognitive traits in contemporary populations constitutes the specific
      contribution of human behavioural ecology to the study of human diversity. Yet,
      despite 30 years of evolutionary anthropological interest in the determinants of
      fitness, there exist few principled investigations of the diverse sources of
      wealth that might reveal selective forces during recent human history. To develop
      a more holistic understanding of how selection shapes human phenotypic traits, be
      these transmitted by genetic or cultural means, we expand the conventional focus
      on associations between socioeconomic status and fitness to three distinct types
      of wealth-embodied, material and relational. Using a model selection approach to
      the study of women's success in raising offspring in an African horticultural
      population (the Tanzanian Pimbwe), we find that the top performing models
      consistently include relational and material wealth, with embodied wealth as a
      less reliable predictor. Specifically, child mortality risk is increased with few
      household assets, parent nonresidency, child legitimacy, and one or more parents
      having been accused of witchcraft. The use of multiple models to test various
      hypotheses greatly facilitates systematic comparative analyses of human
      behavioural diversity in wealth accrual and investment across different kinds of
      societies.

PMID- 21199840
TI  - Flexibility in reproductive timing in human females: integrating ultimate and
      proximate explanations.
AB  - From an ultimate perspective, the age of onset of female reproduction should be
      sensitive to variation in mortality rates, and variation in the productivity of
      non-reproductive activities. In accordance with this prediction, most of the
      cross-national variation in women's age at first birth can be explained by
      differences in female life expectancies and incomes. The within-country variation
      in England shows a similar pattern: women have children younger in neighbourhoods
      where the expectation of healthy life is shorter and incomes are lower. I
      consider the proximate mechanisms likely to be involved in producing locally
      appropriate reproductive decisions. There is evidence suggesting that
      developmental induction, social learning and contextual evocation may all play a
      role.

PMID- 21199841
TI  - Social learning and human mate preferences: a potential mechanism for generating
      and maintaining between-population diversity in attraction.
AB  - Inspired by studies demonstrating mate-choice copying effects in non-human
      species, recent studies of attractiveness judgements suggest that social learning
      also influences human preferences. In the first part of our article, we review
      evidence for social learning effects on preferences in humans and other animals.
      In the second part, we present new empirical evidence that social learning not
      only influences the attractiveness of specific individuals, but can also
      generalize to judgements of previously unseen individuals possessing similar
      physical traits. The different conditions represent different populations and,
      once a preference arises in a population, social learning can lead to the spread
      of preferences within that population. In the final part of our article, we
      discuss the theoretical basis for, and possible impact of, biases in social
      learning whereby individuals may preferentially copy the choices of those with
      high status or better access to critical information about potential mates. Such
      biases could mean that the choices of a select few individuals carry the greatest
      weight, rapidly generating agreement in preferences within a population.
      Collectively, these issues suggest that social learning mechanisms encourage the
      spread of preferences for certain traits once they arise within a population and
      so may explain certain cross-cultural differences.

PMID- 21199842
TI  - Unity and diversity in human language.
AB  - Human language is both highly diverse-different languages have different ways of
      achieving the same functional goals-and easily learnable. Any language allows its
      users to express virtually any thought they can conceptualize. These traits
      render human language unique in the biological world. Understanding the
      biological basis of language is thus both extremely challenging and fundamentally
      interesting. I review the literature on linguistic diversity and language
      universals, suggesting that an adequate notion of 'formal universals' provides a
      promising way to understand the facts of language acquisition, offering order in
      the face of the diversity of human languages. Formal universals are cross
      linguistic generalizations, often of an abstract or implicational nature. They
      derive from cognitive capacities to perceive and process particular types of
      structures and biological constraints upon integration of the multiple systems
      involved in language. Such formal universals can be understood on the model of a
      general solution to a set of differential equations; each language is one
      particular solution. An explicit formal conception of human language that
      embraces both considerable diversity and underlying biological unity is possible,
      and fully compatible with modern evolutionary theory.

PMID- 21199843
TI  - Disgust as an adaptive system for disease avoidance behaviour.
AB  - Disgust is an evolved psychological system for protecting organisms from
      infection through disease avoidant behaviour. This 'behavioural immune system',
      present in a diverse array of species, exhibits universal features that
      orchestrate hygienic behaviour in response to cues of risk of contact with
      pathogens. However, disgust is also a dynamic adaptive system. Individuals show
      variation in pathogen avoidance associated with psychological traits like having
      a neurotic personality, as well as a consequence of being in certain
      physiological states such as pregnancy or infancy. Three specialized learning
      mechanisms modify the disgust response: the Garcia effect, evaluative
      conditioning and the law of contagion. Hygiene behaviour is influenced at the
      group level through social learning heuristics such as 'copy the frequent'.
      Finally, group hygiene is extended symbolically to cultural rules about purity
      and pollution, which create social separations and are enforced as manners.
      Cooperative hygiene endeavours such as sanitation also reduce pathogen
      prevalence. Our model allows us to integrate perspectives from psychology,
      ecology and cultural evolution with those of epidemiology and anthropology.
      Understanding the nature of disease avoidance psychology at all levels of human
      organization can inform the design of programmes to improve public health.

PMID- 21199844
TI  - Macro-evolutionary studies of cultural diversity: a review of empirical studies
      of cultural transmission and cultural adaptation.
AB  - A growing body of theoretical and empirical research has examined cultural
      transmission and adaptive cultural behaviour at the individual, within-group
      level. However, relatively few studies have tried to examine proximate
      transmission or test ultimate adaptive hypotheses about behavioural or cultural
      diversity at a between-societies macro-level. In both the history of anthropology
      and in present-day work, a common approach to examining adaptive behaviour at the
      macro-level has been through correlating various cultural traits with features of
      ecology. We discuss some difficulties with simple ecological associations, and
      then review cultural phylogenetic studies that have attempted to go beyond
      correlations to understand the underlying cultural evolutionary processes. We
      conclude with an example of a phylogenetically controlled approach to
      understanding proximate transmission pathways in Austronesian cultural diversity.

PMID- 21199845
TI  - Modelling the evolution and diversity of cumulative culture.
AB  - Previous work on mathematical models of cultural evolution has mainly focused on
      the diffusion of simple cultural elements. However, a characteristic feature of
      human cultural evolution is the seemingly limitless appearance of new and
      increasingly complex cultural elements. Here, we develop a general modelling
      framework to study such cumulative processes, in which we assume that the
      appearance and disappearance of cultural elements are stochastic events that
      depend on the current state of culture. Five scenarios are explored: evolution of
      independent cultural elements, stepwise modification of elements, differentiation
      or combination of elements and systems of cultural elements. As one application
      of our framework, we study the evolution of cultural diversity (in time as well
      as between groups).

PMID- 21199846
TI  - On the number of independent cultural traits carried by individuals and
      populations.
AB  - In species subject to individual and social learning, each individual is likely
      to express a certain number of different cultural traits acquired during its
      lifetime. If the process of trait innovation and transmission reaches a steady
      state in the population, the number of different cultural traits carried by an
      individual converges to some stationary distribution. We call this the trait
      number distribution. In this paper, we derive the trait-number distributions for
      both individuals and populations when cultural traits are independent of each
      other. Our results suggest that as the number of cultural traits becomes large,
      the trait-number distributions approach Poisson distributions so that their means
      characterize cultural diversity in the population. We then analyse how the mean
      trait number varies at both the individual and population levels as a function of
      various demographic features, such as population size and subdivision, and social
      learning rules, such as conformism and anti-conformism. Diversity at the
      individual and population levels, as well as at the level of cultural homogeneity
      within groups, depends critically on the details of population demography and the
      individual and social learning rules.

PMID- 21199847
TI  - An evaluation of the concept of innateness.
AB  - The concept of innateness is often used in explanations and classifications of
      biological and cognitive traits. But does this concept have a legitimate role to
      play in contemporary scientific discourse? Empirical studies and theoretical
      developments have revealed that simple and intuitively appealing ways of
      classifying traits (e.g. genetically specified versus owing to the environment)
      are inadequate. They have also revealed a variety of scientifically interesting
      ways of classifying traits each of which captures some aspect of the innate/non
      innate distinction. These include things such as whether a trait is canalized,
      whether it has a history of natural selection, whether it developed without
      learning or without a specific set of environmental triggers, whether it is
      causally correlated with the action of certain specific genes, etc. We offer an
      analogy: the term 'jade' was once thought to refer to a single natural kind; it
      was then discovered that it refers to two different chemical compounds, jadeite
      and nephrite. In the same way, we argue, researchers should recognize that
      'innateness' refers not to a single natural kind but to a set of (possibly
      related) natural kinds. When this happens, it will be easier to progress in the
      field of biological and cognitive sciences.

PMID- 21199848
TI  - Exploring the folkbiological conception of human nature.
AB  - Integrating the study of human diversity into the human evolutionary sciences
      requires substantial revision of traditional conceptions of a shared human
      nature. This process may be made more difficult by entrenched, 'folkbiological'
      modes of thought. Earlier work by the authors suggests that biologically naive
      subjects hold an implicit theory according to which some traits are expressions
      of an animal's inner nature while others are imposed by its environment. In this
      paper, we report further studies that extend and refine our account of this
      aspect of folkbiology. We examine biologically naive subjects' judgments about
      whether traits of an animal are 'innate', 'in its DNA' or 'part of its nature'.
      Subjects do not understand these three descriptions to be equivalent. Both innate
      and in its DNA have the connotation that the trait is species-typical. This poses
      an obstacle to the assimilation of the biology of polymorphic and plastic traits
      by biologically naive audiences. Researchers themselves may not be immune to the
      continuing pull of folkbiological modes of thought.

PMID- 21199849
TI  - Human nature, cultural diversity and evolutionary theory.
AB  - Incorporating culture into an expanded theory of evolution will provide the
      foundation for a universal account of human diversity. Two requirements must be
      met. The first is to see learning as an extension of the processes of evolution.
      The second is to understand that there are specific components of human culture,
      viz. higher order knowledge structures and social constructions, which give rise
      to culture as invented knowledge. These components, which are products of
      psychological processes and mechanisms, make human culture different from the
      forms of shared knowledge observed in other species. One serious difficulty for
      such an expanded theory is that social constructions may not add to the fitness
      of all humans exposed to them. This may be because human culture has existed for
      only a relatively short time in evolutionary terms. Or it may be that, as some
      maintain, adaptation is a limited, even a flawed, aspect of evolutionary theory.

PMID- 21199850
TI  - Sense of coherence in mothers and children, family relationships and
      participation in decision-making at home: an analysis based on Japanese parent
      child pair data.
AB  - Children in early adolescence and their mothers were studied to clarify the
      association between a child's sense of coherence (SOC) and its mother's SOC, the
      quality of family relationships as gauged by the mother, and the child's positive
      life experiences at home. An anonymous self-administered group questionnaire was
      given to all 1540 students of a high school in Tokyo, and a similar questionnaire
      was sent by mail to their legal guardians. Responses were received from 1505
      students (response rate: 97.7%) and 989 legal guardians (response rate: 64.2%);
      questionnaires completed by legal guardians who were the mothers of the students
      were paired with the corresponding child's questionnaire. The SOC scores of
      mothers and students were calculated, and hierarchical multiple regression
      analysis was performed with the student's SOC as a dependent variable. Results
      for boys revealed that a mother's SOC was directly related to the child's SOC,
      regardless of family relationships and participation in decision-making at home.
      For girls, a mother's SOC was related to family relationships and was indirectly
      related to the child's SOC through the child's participation in decision-making
      at home. Results revealed that for both boys and girls, a mother's SOC had an
      effect on the child's SOC, and this corroborates the hypothesis of Antonovsky.

PMID- 21199851
TI  - Why should there be an NICHD?
AB  - In its nearly 5 decades of existence, the Eunice Kennedy Shriver National
      Institute of Child Health and Human Development has expended $23 billion in
      conducting and supporting research and translating discoveries to practice. The
      resulting dramatic impact on peoples' lives and improved health for children and
      families, chronicled herein, are a testament to the benefits of having this
      institute at the National Institutes of Health.

PMID- 21199852
TI  - Association between sexually transmitted diseases and young adults' self-reported
      abstinence.
AB  - OBJECTIVE: Self-reported behavior has been the cornerstone of sexual health
      research and clinical practice, yet advances in sexually transmitted disease
      (STD) screening provide researchers with the opportunity to objectively quantify
      sexual risk behaviors. However, the extent to which young adults' laboratory
      confirmed STD results and self-reported sexual behaviors are consistent has not
      been assessed in a nationally representative sample. PATIENTS AND METHODS: Data
      are derived from participants who completed wave 3 in the National Longitudinal
      Study of Adolescent Health. Young adults (N = 14 012) completed an audio computer
      assisted self-interviewing survey and provided a urine specimen to detect the
      presence of Chlamydia trachomatis and Neisseria gonorrhoeae, and a polymerase
      chain reaction assay to detect Trichomonas vaginalis. RESULTS: More than 10% of
      young adults with a laboratory-confirmed positive STD result reported abstaining
      from sexual intercourse in the 12 months before assessment and STD testing. After
      controlling for several sociodemographic factors, self-reported sex (versus those
      who reported abstinence) in the previous 12 months was significantly associated
      with testing positive, but the odds of testing positive were only slightly more
      than twofold (adjusted odds ratio: 2.11 [95% confidence interval: 2.097-2.122]).
      CONCLUSIONS: Findings indicate discrepancy between young adults' positive STD
      status and self-reported sexual behavior. No significant correlates of discrepant
      reporting were identified. From a clinical standpoint, the discrepancies between
      STD positivity and self-reported sexual behavior observed in this nationally
      representative sample suggest that routine STD screening may be beneficial and
      necessary to reduce STD morbidity among young adults.

PMID- 21199854
TI  - Inhalational lung injury associated with humidifier "white dust".
AB  - Humidifiers are commonly used in the community to relieve symptoms associated
      with acute respiratory infections in young children; however, clear benefits of
      these devices have not been documented. The Environmental Protection Agency has
      not found any adverse health effects related to humidifier use. We report here
      the case of a young infant with significant accidental inhalational lung injury
      related to dispersal of mineral dust from an ultrasonic home-use humidifier. The
      clinical consequences included prolonged hypoxemia, tachypnea, and failure to
      thrive. Radiography revealed pneumonitis, and pulmonary-function testing showed a
      nonreversible mild obstructive ventilatory defect. Because of persistent
      symptoms, evolution of failure to thrive, and nonresponse to inhaled and short
      courses of systemic glucocorticoids, an aggressive management approach was
      successfully pursued with high-dose pulse steroid therapy, which could be a
      potential therapeutic approach for similar patients. In addition, this case
      raises important questions about the safety of exposing infants and young
      children to humidifiers and emphasizes the need for further study.

PMID- 21199853
TI  - Hormonal contraception and thrombotic risk: a multidisciplinary approach.
AB  - Heightened publicity about hormonal contraception and thrombosis risk and the
      publication of new guidelines by the World Health Organization in 2009 and the
      Centers for Disease Control and Prevention in 2010 addressing this complex issue
      have led to multidisciplinary discussions on the special issues of adolescents
      cared for at our pediatric hospital. In this review of the literature and new
      guidelines, we have outlined our approach to the complex patients referred to our
      center. The relative risk of thrombosis on combined oral contraception is three-
      to fivefold, whereas the absolute risk for a healthy adolescent on this therapy
      is only 0.05% per year. This thrombotic risk is affected by estrogen dose, type
      of progestin, mechanism of delivery, and length of therapy. Oral progestin-only
      contraceptives and transdermal estradiol used for hormone replacement carry
      minimal or no thrombotic risk. Transdermal, vaginal, or intrauterine
      contraceptives and injectable progestins need further study. A personal history
      of thrombosis, persistent or inherited thrombophilia, and numerous lifestyle
      choices also influence thrombotic risk. In this summary of one hospital's
      approach to hormone therapies and thrombosis risk, we review relative-risk data
      and discuss the application of absolute risk to individual patient counseling. We
      outline our approach to challenging patients with a history of thrombosis, known
      thrombophilia, current anticoagulation, or family history of thrombosis or
      thrombophilia. Our multidisciplinary group has found that knowledge of the
      guidelines and individualized management plans have been particularly useful for
      informing discussions about hormonal and nonhormonal options across varied
      indications.

PMID- 21199855
TI  - The impact of pediatric vision disorders in adulthood.
AB  - In addition to refractive errors such as myopia and astigmatism, ocular disorders
      that occur in infants, toddlers, and children may present lifelong problems for
      the child. Conditions such as strabismus, amblyopia, and retinopathy of
      prematurity may require adaptations in adulthood. In addition, vision disorders
      that occur in childhood may manifest as problems well into adulthood. When visual
      impairment is present, there may be further effects on overall health, self
      perception, educational attainment, job choices, and a number of other social
      factors.

PMID- 21199856
TI  - Fish-oil fat emulsion supplementation may reduce the risk of severe retinopathy
      in VLBW infants.
AB  - OBJECTIVE: The retina contains rods and cones that have membranes highly enriched
      with docosahexaenoic acid (DHA). Infants born prematurely are at risk of DHA
      insufficiency, because they may not have benefited from a full third trimester of
      the mother's lipid stores. Moreover, within the first 2 to 3 weeks of life, the
      main sources of lipids for premature infants are fat emulsions, which do not
      contain DHA. PATIENTS AND METHODS: This observational study was designed to
      compare the safety and efficacy outcomes of an intravenous fat emulsion that
      consists of fish-oil emulsion (contains DHA) with soybean and olive oil,
      administered from the first day of life to 40 infants who weighed <1250 g;
      results were obtained from a historical cohort of 44 preterm neonates who were
      given an emulsion of soybean and olive oil. The primary study outcomes were the
      occurrence of retinopathy and need for laser therapy and cholestasis. Infants in
      the 2 groups were comparable with regard to demographic and clinical
      characteristics and were subjected to the same conventional therapy. RESULTS:
      There was a significantly lower risk of laser therapy for infants who received an
      emulsion of soybean, olive oil, and fish oil (P = .023). No significant
      differences were found in acuity and latency of visual evoked potentials between
      infants in the 2 groups. There was no infant with cholestasis among those who
      received fish-oil emulsion, and there were 5 subjects with cholestasis in the
      historical group (P = .056). CONCLUSION: Fish-oil-based fat emulsion administered
      from the first day of life may be effective in the prophylaxis of severe
      retinopathy.

PMID- 21199857
TI  - Varicella-related hospitalizations in the United States, 2000-2006: the 1-dose
      varicella vaccination era.
AB  - OBJECTIVE: To describe the effect of the mature 1-dose varicella vaccination
      program on varicella morbidity, we analyzed 2 national databases for varicella
      related hospitalizations in the United States since implementation of the
      varicella vaccination program in 1995. PATIENTS AND METHODS: Data from the
      National Hospital Discharge Survey and Nationwide Inpatient Sample were analyzed
      to describe trends in varicella-related hospitalizations during the 1-dose
      vaccination era (2000-2006) compared with those in the prevaccination era (1988
      1995). Varicella-related hospitalizations were defined by using International
      Classification of Diseases, Ninth Revision codes. Results were extrapolated to
      represent national estimates. RESULTS: Using National Hospital Discharge Survey
      data, 24,488 varicella-related hospitalizations were estimated to occur in the
      United States during the 1-dose vaccination era. The varicella-related
      hospitalization rate was 0.12 per 10,000 population during the 1-dose vaccination
      era versus 0.42 per 10,000 population in the prevaccination era (P < .01). During
      the 1-dose vaccination era, the estimated annual average number of varicella
      related hospitalizations was significantly lower and decreased by >= 65% in all
      age groups compared with those in the prevaccination era (P < .001 in all age
      groups). The varicella-related hospitalization rate during the 1-dose vaccination
      era estimated from the Nationwide Inpatient Sample was 0.09 per 10,000
      population. CONCLUSIONS: Varicella-related hospitalization numbers and rates
      declined significantly during the 1-dose varicella vaccination era. Assuming
      declines in varicella-related hospitalizations are due, mainly, to the routine
      childhood varicella vaccination program, these data suggest that varicella
      vaccination prevented ~ 50,000 varicella-related hospitalizations in the United
      States from 2000 to 2006.

PMID- 21199858
TI  - Lingual dyskinesia and tics: a novel presentation of copper-metabolism disorder.
AB  - Copper is a trace element that is required for cellular respiration,
      neurotransmitter biosynthesis, pigment formation, antioxidant defense, peptide
      amidation, and formation of connective tissue. Abnormalities of copper metabolism
      have been linked with neurologic disorders that affect movement, such as Wilson
      disease and Menkes disease; however, the diagnosis of non-Wilson, non-Menkes-type
      copper-metabolism disorders has been more elusive, especially in cases with
      atypical characteristics. We present here the case of an adolescent with a novel
      presentation of copper-metabolism disorder who exhibited acute severe hemilingual
      dyskinesia and prominent tics, with ballismus of the upper limbs, but had normal
      brain and spinal MRI results and did not show any signs of dysarthria or
      dysphagia. His serum copper and ceruloplasmin levels were low, but his urinary
      copper level was elevated after penicillamine challenge. We conclude that copper
      metabolism disorders should be included in the differential diagnosis for
      movement disorders, even in cases with highly unusual presentations, because many
      of them are treatable. Moreover, a connection between copper-metabolism disorders
      and tics is presented, to our knowledge, for the first time in humans; further
      investigation is needed to better establish this connection and understand its
      underlying pathophysiology.

PMID- 21199859
TI  - Wolfram syndrome 1 gene (WFS1) product localizes to secretory granules and
      determines granule acidification in pancreatic beta-cells.
AB  - Wolfram syndrome is an autosomal recessive disorder characterized by juvenile
      onset insulin-dependent diabetes mellitus and optic atrophy. The gene responsible
      for the syndrome (WFS1) encodes an endoplasmic reticulum (ER) resident
      transmembrane protein. The Wfs1-null mouse exhibits progressive insulin
      deficiency causing diabetes. Previous work suggested that the function of the
      WFS1 protein is connected to unfolded protein response and to intracellular
      Ca(2+) homeostasis. However, its precise molecular function in pancreatic beta
      cells remains elusive. In our present study, immunofluorescent and electron
      microscopic analyses revealed that WFS1 localizes not only to ER but also to
      secretory granules in pancreatic beta-cells. Intragranular acidification was
      assessed by measuring intracellular fluorescence intensity raised by the
      acidotrophic agent, 3-[2,4-dinitroanilino]-3'-amino-N-methyldipropyramine.
      Compared with wild-type beta-cells, there was a 32% reduction in the intensity in
      WFS1-deficient beta-cells, indicating the impairment of granular acidification.
      This phenotype may, at least partly, account for the evidence that Wfs1-null
      islets have impaired proinsulin processing, resulting in an increased circulating
      proinsulin level. Morphometric analysis using electron microscopy evidenced that
      the density of secretory granules attached to the plasma membrane was
      significantly reduced in Wfs1-null beta-cells relative to that in wild-type beta
      cells. This may be relevant to the recent finding that granular acidification is
      required for the priming of secretory granules preceding exocytosis and may
      partly explain the fact that glucose-induced insulin secretion is profoundly
      impaired in young prediabetic Wfs1-null mice. These results thus provide new
      insights into the molecular mechanisms of beta-cell dysfunction in patients with
      Wolfram syndrome.

PMID- 21199860
TI  - Over-expression of BCL2 rescues muscle weakness in a mouse model of
      oculopharyngeal muscular dystrophy.
AB  - Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscular dystrophy
      caused by a polyalanine expansion mutation in the coding region of the poly-(A)
      binding protein nuclear 1 (PABPN1) gene. In unaffected individuals, (GCG)(6)
      encodes the first 6 alanines in a homopolymeric stretch of 10 alanines. In most
      patients, this (GCG)(6) repeat is expanded to (GCG)(8-13), leading to a stretch
      of 12-17 alanines in mutant PABPN1, which is thought to confer a toxic gain of
      function. Thus, OPMD has been modelled by expressing mutant PABPN1 transgenes in
      the presence of endogenous copies of the gene in cells and mice. In these models,
      increased apoptosis is seen, but it is unclear whether this process mediates
      OPMD. The role of apoptosis in the pathogenesis of different muscular dystrophies
      is unclear. Blocking apoptosis ameliorates muscle disease in some mouse models of
      muscular dystrophy such as laminin alpha-2-deficient mice, but not in others such
      as dystrophin-deficient (mdx) mice. Here we demonstrate that apoptosis is not
      only involved in the pathology of OPMD but also is a major contributor to the
      muscle weakness and dysfunction in this disease. Genetically blocking apoptosis
      by over-expressing BCL2 ameliorates muscle weakness in our mouse model of OPMD
      (A17 mice). The effect of BCL2 co-expression on muscle weakness is transient,
      since muscle weakness is apparent in mice expressing both A17 and BCL2 transgenes
      at late time points. Thus, while apoptosis is a major pathway that causes muscle
      weakness in OPMD, other cell death pathways may also contribute to the disease
      when apoptosis is inhibited.

PMID- 21199861
TI  - Predicting the transition from acute to persistent low back pain.
AB  - BACKGROUND: Most people experience low back pain (LBP) at least once in their
      lifetime. Only a minority of them go on to develop persistent LBP. However, the
      socioeconomic costs of persistent LBP significantly exceed the costs of the
      initial acute LBP episode. AIMS: To identify factors that influence the
      progression of acute LBP to the persistent state at an early stage. METHODS:
      Prospective inception cohort study of patients attending a health practitioner
      for their first episode of acute LBP or recurrent LBP after a pain free period of
      at least 6 months. Patients were assessed at baseline addressing occupational and
      psychological factors as well as pain, disability, quality of life and physical
      activity and followed up at 3, 6, 12 weeks and 6 months. Variables were combined
      to the three indices 'working condition', 'depression and maladaptive cognitions'
      and 'pain and quality of life'. RESULTS: The index 'depression and maladaptive
      cognitions' was found to be a significant baseline predictor for persistent LBP
      up to 6 months (OR 5.1; 95% CI: 1.04-25.1). Overall predictive accuracy of the
      model was 81%. CONCLUSIONS: In this study of patients with acute LBP in a primary
      care setting psychological factors at baseline correlated with a progression to
      persistent LBP up to 6 months. The benefit of including factors such as
      'depression and maladaptive cognition' in screening tools is that these factors
      can be addressed in primary and secondary prevention.

PMID- 21199862
TI  - Support to aging parents and grown children in Black and White families.
AB  - PURPOSE: Black and White middle-aged adults typically are in a pivot position of
      providing support to generations above and below. Racial differences in support
      to each generation in the family remain unclear, however. Different factors may
      account for racial differences in support of grown children versus aging parents.
      DESIGN AND METHODS: Middle-aged adults (aged 40-60 years; 35%, n = 216 Black and
      65%, n = 397 White) rated social support they provided each aging parent and
      grown child. Participants reported background characteristics representing their
      resources and measures of needs for each family member. Interviews also assessed
      beliefs about obligation to support parents and grown children and rewards from
      helping. RESULTS: Multilevel models revealed White middle-aged adults provided
      more support to grown children than Black middle-aged adults. Demands from
      offspring, beliefs about support, and rewards from helping explained these racial
      differences. Black middle-aged adults provided more support to parents than White
      middle-aged adults. Beliefs about support and feelings of personal reward from
      providing support explained this difference but resources and demands did not.
      IMPLICATIONS: Racial differences varied by generation (parent or offspring). The
      prolonged transitions common for White young adults explained racial differences
      in support of offspring. Middle-aged adults may treat support of parents as more
      discretionary, with cultural ideas about obligation and personal rewards guiding
      behaviors.

PMID- 21199863
TI  - The Ca2+-dependent phosphatase calcineurin controls the formation of the Carma1
      Bcl10-Malt1 complex during T cell receptor-induced NF-kappaB activation.
AB  - T cell receptor (TCR) ligation induces increased diacylglycerol and Ca(2+) levels
      in T cells, and both secondary messengers are crucial for TCR-induced nuclear
      factor of activated T cells (NF-AT) and NF-kappaB signaling pathways. One
      prominent calcium-dependent enzyme involved in the regulation of NF-AT and NF
      kappaB signaling pathways is the protein phosphatase calcineurin. However, in
      contrast to NF-AT, which is directly dephosphorylated by calcineurin, the
      molecular basis of the calcium-calcineurin dependence of the TCR-induced NF
      kappaB activity remains largely unknown. Here, we demonstrate that calcineurin
      regulates TCR-induced NF-kappaB activity by controlling the formation of a
      protein complex composed of Carma1, Bcl10, and Malt1 (CBM complex). For instance,
      increased calcium levels induced by ionomycin or thapsigargin augmented the
      phorbol 12-myristate 13-acetate-induced formation of the CBM complex and
      activation of NF-kappaB, whereas removal of calcium by the calcium chelator EGTA
      acetoxymethyl ester (AM) attenuated both processes. Furthermore, inhibition of
      the calcium-dependent phosphatase calcineurin with the immunosuppressive agent
      cyclosporin A (CsA) or FK506 as well as siRNA-mediated knockdown of calcineurin A
      strongly affected the PMA + ionomycin- or anti-CD3 + CD28-induced CBM complex
      assembly. Mechanistically, the positive effect of calcineurin on the CBM complex
      formation seems to be linked to a dephosphorylation of Bcl10. For instance, Bcl10
      was found to be hyperphosphorylated in Jurkat T cells upon treatment with CsA or
      EGTA-AM, and calcineurin dephosphorylated Bcl10 in vivo and in vitro.
      Furthermore, we show here that calcineurin A interacts with the CBM complex. In
      summary, the evidence provided here argues for a previously unanticipated role of
      calcineurin in CBM complex formation as a molecular basis of the inhibitory
      function of CsA or FK506 on TCR-induced NF-kappaB activity.

PMID- 21199864
TI  - A microarray-based approach identifies ADP ribosylation factor-like protein 2 as
      a target of microRNA-16.
AB  - microRNAs (miRNAs) are generally thought to negatively regulate the expression of
      their target genes by mRNA degradation or by translation repression. Here we show
      an efficient way to identify miRNA target genes by screening alterations in
      global mRNA levels following changes in miRNA levels. In this study, we used mRNA
      microarrays to measure global mRNA expression in three cell lines with increased
      or decreased levels of miR-16 and performed bioinformatics analysis based on
      multiple target prediction algorithms. For further investigation among the
      predicted miR-16 target genes, we selected genes that show an expression pattern
      opposite to that of miR-16. One of the candidate target genes that may interact
      with miR-16, ADP-ribosylation factor-like protein 2 (ARL2), was further
      investigated. First, ARL2 was deduced to be an ideal miR-16 target by
      computational predictions. Second, ARL2 mRNA and protein levels were
      significantly abolished by treatment with miR-16 precursors, whereas a miR-16
      inhibitor increased ARL2 mRNA and protein levels. Third, a luciferase reporter
      assay confirmed that miR-16 directly recognizes the 3'-untranslated region (3'
      UTR) of ARL2. Finally, we showed that miR-16 could regulate proliferation and
      induce a significant G0/G1 cell cycle arrest, which was due at least in part, to
      the down-regulation of ARL2. In summary, the present study suggests that
      integrating global mRNA profiling and bioinformatics tools may provide the basis
      for further investigation of the potential targets of a given miRNA. These
      results also illustrate a novel function of miR-16 targeting ARL2 in modulating
      proliferation and cell cycle progression.

PMID- 21199865
TI  - Mutation to Bax beyond the BH3 domain disrupts interactions with pro-survival
      proteins and promotes apoptosis.
AB  - Pro-survival members of the Bcl-2 family of proteins restrain the pro-apoptotic
      activity of Bax, either directly through interactions with Bax or indirectly by
      sequestration of activator BH3-only proteins, or both. Mutations in Bax that
      promote apoptosis can provide insight into how Bax is regulated. Here, we
      describe crystal structures of the pro-survival proteins Mcl-1 and Bcl-x(L) in
      complex with a 34-mer peptide from Bax that encompasses its BH3 domain. These
      structures reveal canonical interactions between four signature hydrophobic amino
      acids from the BaxBH3 domain and the BH3-binding groove of the pro-survival
      proteins. In both structures, Met-74 from the Bax peptide engages with the BH3
      binding groove in a fifth hydrophobic interaction. Various Bax Met-74 mutants
      disrupt interactions between Bax and all pro-survival proteins, but these Bax
      mutants retain pro-apoptotic activity. Bax/Bak-deficient mouse embryonic
      fibroblast cells reconstituted with several Bax Met-74 mutants are more sensitive
      to the BH3 mimetic compound ABT-737 as compared with cells expressing wild-type
      Bax. Furthermore, the cells expressing Bax Met-74 mutants are less viable in
      colony assays even in the absence of an external apoptotic stimulus. These
      results support a model in which direct restraint of Bax by pro-survival Bcl-2
      proteins is a barrier to apoptosis.

PMID- 21199867
TI  - Structural basis for recognition of urokinase-type plasminogen activator by
      plasminogen activator inhibitor-1.
AB  - Plasminogen activator inhibitor-1 (PAI-1), together with its physiological target
      urokinase-type plasminogen activator (uPA), plays a pivotal role in fibrinolysis,
      cell migration, and tissue remodeling and is currently recognized as being among
      the most extensively validated biological prognostic factors in several cancer
      types. PAI-1 specifically and rapidly inhibits uPA and tissue-type PA (tPA).
      Despite extensive structural/functional studies on these two reactions, the
      underlying structural mechanism has remained unknown due to the technical
      difficulties of obtaining the relevant structures. Here, we report a strategy to
      generate a PAI-1.uPA(S195A) Michaelis complex and present its crystal structure
      at 2.3-A resolution. In this structure, the PAI-1 reactive center loop serves as
      a bait to attract uPA onto the top of the PAI-1 molecule. The P4-P3' residues of
      the reactive center loop interact extensively with the uPA catalytic site,
      accounting for about two-thirds of the total contact area. Besides the active
      site, almost all uPA exosite loops, including the 37-, 60-, 97-, 147-, and 217
      loops, are involved in the interaction with PAI-1. The uPA 37-loop makes an
      extensive interaction with PAI-1 beta-sheet B, and the 147-loop directly contacts
      PAI-1 beta-sheet C. Both loops are important for initial Michaelis complex
      formation. This study lays down a foundation for understanding the specificity of
      PAI-1 for uPA and tPA and provides a structural basis for further functional
      studies.

PMID- 21199866
TI  - Conserved intramolecular disulfide bond is critical to trafficking and fate of
      ATP-binding cassette (ABC) transporters ABCB6 and sulfonylurea receptor 1
      (SUR1)/ABCC8.
AB  - The ATP-binding cassette (ABC) transporter ABCB6 is a mitochondrial porphyrin
      transporter that activates porphyrin biosynthesis. ABCB6 lacks a canonical
      mitochondrial targeting sequence but reportedly traffics to other cellular
      compartments such as the plasma membrane. How ABCB6 reaches these destinations is
      unknown. In this study, we show that endogenous ABCB6 is glycosylated in multiple
      cell types, indicating trafficking through the endoplasmic reticulum (ER), and
      has only one atypical site for glycosylation (NXC) in its amino terminus. ABCB6
      remained glycosylated when the highly conserved cysteine (Cys-8) was substituted
      with serine to make a consensus site, NXS. However, this substitution blocked ER
      exit and produced ABCB6 degradation, which was mostly reversed by the proteasomal
      inhibitor MG132. The amino terminus of ABCB6 has an additional highly conserved
      ER luminal cysteine (Cys-26). When Cys-26 was mutated alone or in combination
      with Cys-8, it also resulted in instability and ER retention. Further analysis
      revealed that these two cysteines form a disulfide bond. We discovered that other
      ABC transporters with an amino terminus in the ER had similarly configured
      conserved cysteines. This analysis led to the discovery of a disease-causing
      mutation in the sulfonylurea receptor 1 (SUR1)/ABCC8 from a patient with
      hyperinsulinemic hypoglycemia. The mutant allele only contains a mutation in a
      conserved amino-terminal cysteine, producing SUR1 that fails to reach the cell
      surface. These results suggest that for ABC transporters the propensity to form a
      disulfide bond in the ER defines a unique checkpoint that determines whether a
      protein is ER-retained.

PMID- 21199868
TI  - Identification of SPRED2 (sprouty-related protein with EVH1 domain 2) as a
      negative regulator of the hypothalamic-pituitary-adrenal axis.
AB  - Sprouty-related proteins with EVH1 (enabled/vasodilator-stimulated phosphoprotein
      homology 1) domain (SPREDs) are inhibitors of MAPK signaling. To elucidate SPRED2
      in vivo function, we characterized body homeostasis in SPRED2(-/-) mice. They
      showed a doubled daily water uptake, induced by elevated serum osmolality,
      originating from increased blood salt load. Accordingly, serum aldosterone was
      doubled, accompanied by augmented adrenal aldosterone synthase (AS) expression.
      Surprisingly, serum vasopressin (AVP) was unaltered, and, as evidenced by halved
      angiotensin II (Ang II) levels, the renin angiotensin system (RAS) was down
      regulated. Adrenocorticotropic hormone (ACTH) was significantly elevated in
      SPRED2(-/-) mice, together with its secretagogue corticotropin-releasing hormone
      (CRH) and its downstream target corticosterone. ERK phosphorylation in brains was
      augmented, and hypothalamic CRH mRNA levels were elevated, both contributing to
      the increased CRH release. Our data were supported by CRH promoter reporter
      assays in hypothalamic mHypoE-44 cells, revealing a SPRED-dependent inhibition of
      Ets (ERK/E-twenty-six)-dependent transcription. Furthermore, SPRED suppressed CRH
      production in these cells. In conclusion, our study suggests that SPRED2
      deficiency leads to an increased MAPK signaling, which results in an augmented
      CRH promoter activity. The subsequent CRH overproduction causes an up-regulation
      of downstream hypothalamic-pituitary-adrenal (HPA) hormone secretion. This
      constitutes a possible trigger for the observed compulsive grooming in SPRED2(-/
      ) mice and may, together with hyperplasia of aldosterone-producing cells,
      contribute to the hyperaldosteronism and homeostatic imbalances.

PMID- 21199869
TI  - Recognition in the face of diversity: interactions of heterotrimeric G proteins
      and G protein-coupled receptor (GPCR) kinases with activated GPCRs.
AB  - G protein-coupled receptors (GPCRs) represent the largest class of integral
      membrane protein receptors in the human genome. Despite the great diversity of
      ligands that activate these GPCRs, they interact with a relatively small number
      of intracellular proteins to induce profound physiological change. Both
      heterotrimeric G proteins and GPCR kinases are well known for their ability to
      specifically recognize GPCRs in their active state. Recent structural studies now
      suggest that heterotrimeric G proteins and GPCR kinases identify activated
      receptors via a common molecular mechanism despite having completely different
      folds.

PMID- 21199870
TI  - Single particle tracking confirms that multivalent Tat protein transduction
      domain-induced heparan sulfate proteoglycan cross-linkage activates Rac1 for
      internalization.
AB  - The mechanism by which HIV-1-Tat protein transduction domain (TatP) enters the
      cell remains unclear because of an insufficient understanding of the initial
      kinetics of peptide entry. Here, we report the successful visualization and
      tracking of TatP molecular kinetics on the cell surface with 7-nm spatial
      precision using quantum dots. Strong cell binding was only observed with a TatP
      valence of >=8, whereas monovalent TatP binding was negligible. The requirement
      of the cell-surface heparan sulfate (HS) chains of HS proteoglycans (HSPGs) for
      TatP binding and intracellular transport was demonstrated by the enzymatic
      removal of HS and simultaneous observation of two individual particles.
      Multivalent TatP induces HSPG cross-linking, recruiting activated Rac1 to
      adjacent lipid rafts and thereby enhancing the recruitment of TatP/HSPG to actin
      associated microdomains and its internalization by macropinocytosis. These
      findings clarify the initial binding mechanism of TatP to the cell surface and
      demonstrate the importance of TatP valence for strong surface binding and signal
      transduction. Our data also shed light on the ability of TatP to exploit the
      machinery of living cells, using HSPG signaling to activate Rac1 and alter TatP
      mobility and internalization. This work should guide the future design of TatP
      based peptides as therapeutic nanocarriers with efficient transduction.

PMID- 21199871
TI  - Inhibition of MAPK by prolactin signaling through the short form of its receptor
      in the ovary and decidua: involvement of a novel phosphatase.
AB  - Prolactin (PRL) is essential for normal reproduction and signals through two
      types of receptors, the short (PRL-RS) and long (PRL-RL) form. We have previously
      shown that transgenic mice expressing only PRL-RS (PRLR(-/-)RS) display abnormal
      follicular development and premature ovarian failure. Here, we report that MAPK,
      essential for normal follicular development, is critically inhibited by PRL in
      reproductive tissues of PRLR(-/-)RS mice. Consequently, the phosphorylation of
      MAPK downstream targets are also markedly inhibited by PRL without affecting
      immediate upstream kinases, suggesting involvement of MAPK specific
      phosphatase(s) in this inhibition. Similar results are obtained in a PRL
      responsive ovary-derived cell line (GG-CL) that expresses only PRL-RS. However,
      we found the expression/activation of several known MAPK phosphatases not to be
      affected by PRL, suggesting a role of unidentified phosphatase(s). We detected a
      27-kDa protein that binds to the intracellular domain of PRL-RS and identified it
      as dual specific phosphatase DUPD1. PRL does not induce expression of DUDP1 but
      represses its phosphorylation on Thr-155. We also show a physical association of
      this phosphatase with ERK1/2 and p38 MAPK. Using an in vitro phosphatase assay
      and overexpression studies, we established that DUPD1 is a MAPK phosphatase. Dual
      specific phosphatase inhibitors as well as siRNA to DUPD1, completely prevent PRL
      mediated MAPK inhibition in ovarian cells. Our results strongly suggest that
      deactivation of MAPK by PRL/PRL-RS contributes to the severe ovarian defect in
      PRLR(-/-)RS mice and demonstrate the novel association of PRL-RS with DUPD1 and a
      role for this phosphatase in MAPK deactivation.

PMID- 21199872
TI  - PIASy inhibits virus-induced and interferon-stimulated transcription through
      distinct mechanisms.
AB  - The protein inhibitor of activated STAT (PIAS) family proteins regulates innate
      immune responses by controlling transcription induced by Toll-like receptor, RIG
      I-like receptor signaling, and JAK/STAT pathways. Here, we show that PIASy
      negatively regulates type I interferon (IFN) transcription. Virus infection led
      to enhanced type I IFN induction in PIASy null cells, and conversely PIASy
      overexpression reduced IFN transcription. A mutation in the LXXLL motif of the
      SAP domain abolished inhibition of IFN-stimulated gene expression but did not
      affect virus or Toll-like receptor/RIG-I-like receptor-stimulated IFN
      transcription, indicating that PIASy employs distinct mechanisms to inhibit virus
      induced and IFN-stimulated transcription. SUMO E3 activity was not required for
      PIASy inhibition of IFN transcription; however, PIASy relied on the SUMO
      modification mechanism to inhibit IFN transcription, because the activity of the
      SUMO-interacting motif was required for inhibition, and knockdown of SUMO E2
      enzyme UBC9 decreased inhibitory activity of PIASy. Our results demonstrate that
      PIASy negatively regulates both IFN transcription and IFN-stimulated gene
      expression through multiple mechanisms utilizing the function of different
      domains.

PMID- 21199873
TI  - Simvastatin prevents skeletal metastasis of breast cancer by an antagonistic
      interplay between p53 and CD44.
AB  - Substantial data from clinical trials and epidemiological studies show promising
      results for use of statins in many cancers, including mammary carcinoma. Breast
      tumor primarily metastasizes to bone to form osteolytic lesions, causing severe
      pain and pathological fracture. Here, we report that simvastatin acts as an
      inhibitor of osteolysis in a mouse model of breast cancer skeletal metastasis of
      human mammary cancer cell MDA-MB-231, which expresses the mutant p53R280K.
      Simvastatin and lovastatin attenuated migration and invasion of MDA-MB-231 and BT
      20 breast tumor cells in culture. Acquisition of phenotype to express the cancer
      stem cell marker, CD44, leads to invasive potential of the tumor cells.
      Interestingly, statins significantly decreased the expression of CD44 protein via
      a transcriptional mechanism. shRNA-mediated down-regulation of CD44 markedly
      reduced the migration and invasion of breast cancer cells in culture. We
      identified that in the MDA-MB-231 cells, simvastatin elevated the levels of
      mutated p53R280K, which was remarkably active as a transcription factor. shRNA
      derived inhibition of mutant p53R280K augmented the expression of CD44, leading
      to increased migration and invasion. Finally, we demonstrate an inverse
      correlation between expression of p53 and CD44 in the tumors of mice that
      received simvastatin. Our results reveal a unique function of statins, which
      foster enhanced expression of mutant p53R280K to prevent breast cancer cell
      metastasis to bone.

PMID- 21199874
TI  - Study of the thiol/disulfide redox systems of the anaerobe Desulfovibrio vulgaris
      points out pyruvate:ferredoxin oxidoreductase as a new target for thioredoxin 1.
AB  - Sulfate reducers have developed a multifaceted adaptative strategy to survive
      against oxidative stresses. Along with this oxidative stress response, we
      recently characterized an elegant reversible disulfide bond-dependent protective
      mechanism in the pyruvate:ferredoxin oxidoreductase (PFOR) of various
      Desulfovibrio species. Here, we searched for thiol redox systems involved in this
      mechanism. Using thiol fluorescent labeling, we show that glutathione is not the
      major thiol/disulfide balance-controlling compound in four different
      Desulfovibrio species and that no other plentiful low molecular weight thiol can
      be detected. Enzymatic analyses of two thioredoxins (Trxs) and three thioredoxin
      reductases allow us to propose the existence of two independent Trx systems in
      Desulfovibrio vulgaris Hildenborough (DvH). The TR1/Trx1 system corresponds to
      the typical bacterial Trx system. We measured a TR1 apparent K(m) value for Trx1
      of 8.9 MUM. Moreover, our results showed that activity of TR1 was NADPH
      dependent. The second system named TR3/Trx3 corresponds to an unconventional Trx
      system as TR3 used preferentially NADH (K(m) for NADPH, 743 MUM; K(m) for NADH,
      5.6 MUM), and Trx3 was unable to reduce insulin. The K(m) value of TR3 for Trx3
      was 1.12 MUM. In vitro experiments demonstrated that the TR1/Trx1 system was the
      only one able to reactivate the oxygen-protected form of Desulfovibrio africanus
      PFOR. Moreover, ex vivo pulldown assays using the mutant Trx1(C33S) as bait
      allowed us to capture PFOR from the DvH extract. Altogether, these data
      demonstrate that PFOR is a new target for Trx1, which is probably involved in the
      protective switch mechanism of the enzyme.

PMID- 21199875
TI  - Novel double-negative feedback loop between adenomatous polyposis coli and
      Musashi1 in colon epithelia.
AB  - Loss of tumor suppressor adenomatous polyposis coli (APC) is thought to initiate
      the majority of all colorectal cancers. The predominant theory of colorectal
      carcinogenesis implicates stem cells as the initiating cells. However, relatively
      little is known about the function of APC in governing the homeostasis of normal
      intestinal stem cells. Here, we identify a novel double-negative feedback loop
      between APC and a translation inhibitor protein, Musashi1 (MSI1), in cultured
      human colonocytes. We show APC as a key factor in MSI1 regulation through Wnt
      signaling and identify APC mRNA as a novel target of translational inhibition by
      MSI1. We propose that APC/MSI1 interactions maintain homeostatic balance in the
      intestinal epithelium.

PMID- 21199876
TI  - Regulation of inducible nitric-oxide synthase by the SPRY domain- and SOCS box
      containing proteins.
AB  - Inducible nitric-oxide synthase (iNOS, NOS2) plays a prominent role in macrophage
      bactericidal and tumoricidal activities. A relatively large amount of NO produced
      via iNOS, however, also targets the macrophage itself for apoptotic cell death.
      To uncover the intrinsic mechanisms of iNOS regulation, we have characterized the
      SPRY domain- and SOCS box-containing protein 1 (SPSB1), SPSB2, and SPSB4 that
      interact with the N-terminal region of iNOS in a D-I-N-N-N sequence-dependent
      manner. Fluorescence microscopy revealed that these SPSB proteins can induce the
      subcellular redistribution of iNOS from dense regions to diffused expression in a
      SOCS box-dependent manner. In immunoprecipitation studies, both Elongin C and
      Cullin-5, components of the multi-subunit E3 ubiquitin ligase, were found to bind
      to iNOS via SPSB1, SPSB2, or SPSB4. Consistently, iNOS was polyubiquitinated and
      degraded in a proteasome-dependent manner when SPSB1, SPSB2, or SPSB4 was
      expressed. SPSB1 and SPSB4 had a greater effect on iNOS regulation than SPSB2.
      The iNOS N-terminal fragment (residues 1-124 of human iNOS) could disrupt iNOS
      SPSB interactions and inhibit iNOS degradation. In lipopolysaccharide-treated
      macrophages, this fragment attenuated iNOS ubiquitination and substantially
      prolonged iNOS lifetime, resulting in a corresponding increase in NO production
      and enhanced NO-dependent cell death. These results not only demonstrate the
      mechanism of SPSB-mediated iNOS degradation and the relative contributions of
      different SPSB proteins to iNOS regulation, but also show that iNOS levels are
      sophisticatedly regulated by SPSB proteins in activated macrophages to prevent
      overproduction of NO that could trigger detrimental effects, such as
      cytotoxicity.

PMID- 21199877
TI  - The tumor suppressor RASSF1A prevents dephosphorylation of the mammalian STE20
      like kinases MST1 and MST2.
AB  - The RASSF1A tumor suppressor protein interacts with the pro-apoptotic mammalian
      STE20-like kinases MST1 and MST2 and induces their autophosphorylation and
      activation, but the mechanism of how RASSF1A activates MST1/2 is unclear. Okadaic
      acid treatment and PP2A knockdown promoted MST1/2 phosphorylation. Data from
      dephosphorylation assays and reduced activation of MST1/2 seen after RASSF1A
      depletion suggest that dephosphorylation of MST1/2 on Thr-183 and Thr-180 by PP2A
      is prevented by RASSF1A, shifting the balance of MST1/2 to the activated
      autophosphorylated form. In addition to preventing dephosphorylation, RASSF1A
      also stabilized the MST2 protein. Through binding to MST1/2, RASSF1A supports
      maintenance of MST1/2 phosphorylation, promoting an active state of the MST
      kinases and favoring induction of apoptosis. This is one of the first examples of
      a tumor suppressor acting as an inhibitor of a specific dephosphorylation
      pathway.

PMID- 21199879
TI  - Cell wall biology: perspectives from cell wall imaging.
AB  - Polysaccharide-rich plant cell walls are important biomaterials that underpin
      plant growth, are major repositories for photosynthetically accumulated carbon,
      and, in addition, impact greatly on the human use of plants. Land plant cell
      walls contain in the region of a dozen major polysaccharide structures that are
      mostly encompassed by cellulose, hemicelluloses, and pectic polysaccharides.
      During the evolution of land plants, polysaccharide diversification appears to
      have largely involved structural elaboration and diversification within these
      polysaccharide groups. Cell wall chemistry is well advanced and a current phase
      of cell wall science is aimed at placing the complex polysaccharide chemistry in
      cellular contexts and developing a detailed understanding of cell wall biology.
      Imaging cell wall glycomes is a challenging area but recent developments in the
      establishment of cell wall molecular probe panels and their use in high
      throughput procedures are leading to rapid advances in the molecular
      understanding of the spatial heterogeneity of individual cell walls and also cell
      wall differences at taxonomic levels. The challenge now is to integrate this
      knowledge of cell wall heterogeneity with an understanding of the molecular and
      physiological mechanisms that underpin cell wall properties and functions.

PMID- 21199878
TI  - Stoichiometric relationship among clock proteins determines robustness of
      circadian rhythms.
AB  - The mammalian circadian oscillator is primarily driven by an essential negative
      feedback loop comprising a positive component, the CLOCK-BMAL1 complex, and a
      negative component, the PER-CRY complex. Numerous studies suggest that feedback
      inhibition of CLOCK-BMAL1 is mediated by time-dependent physical interaction with
      its direct target gene products PER and CRY, suggesting that the ratio between
      the negative and positive complexes must be important for the molecular
      oscillator and rhythm generation. We explored this idea by altering expression of
      clock components in fibroblasts derived from Per2(Luc) and Per mutant mice, a
      cell system extensively used to study in vivo clock mechanisms. Our data
      demonstrate that the stoichiometric relationship between clock components is
      critical for the robustness of circadian rhythms and provide insights into the
      mechanistic organization of the negative feedback loop. Our findings may explain
      why certain mutant mice or cells are arrhythmic, whereas others are rhythmic, and
      suggest that robustness of circadian rhythms can be increased even in wild-type
      cells by modulating the stoichiometry.

PMID- 21199880
TI  - Dihydrosphingosine-induced programmed cell death in tobacco BY-2 cells is
      independent of H2O2 production.
AB  - Sphinganine or dihydrosphingosine (d18:0, DHS), one of the most abundant free
      sphingoid Long Chain Base (LCB) in plants, has been recently shown to induce both
      cytosolic and nuclear calcium transient increases and a correlated Programmed
      Cell Death (PCD) in tobacco BY-2 cells. In this study, in order to get deeper
      insight into the LCB signaling pathway leading to cell death, the putative role
      of Reactive Oxygen Species (ROS) has been investigated. We show that DHS triggers
      a rapid dose-dependent production of H2O2 that is blocked by diphenyleniodonium
      (DPI), indicating the involvement of NADPH oxidase(s) in the process. In
      addition, while DPI does not block DHS-induced calcium increases, the ROS
      production is inhibited by the broad spectrum calcium channel blocker lanthanum
      (La3+). Therefore, ROS production occurs downstream of DHS-induced Ca2+
      transients. Interestingly, DHS activates expression of defense-related genes that
      is inhibited by both La3+ and DPI. Since DPI does not prevent DHS-induced cell
      death, these results strongly indicate that DHS-induced H2O2 production is not
      implicated in PCD mechanisms but rather would be associated to basal cell defense
      mechanisms.

PMID- 21199881
TI  - Impact of malaria at the end of pregnancy on infant mortality and morbidity.
AB  - BACKGROUND: There is some consensus that malaria in pregnancy may negatively
      affect infant's mortality and malaria morbidity, but there is less evidence
      concerning the factors involved. METHODS: A total of 1030 Mozambican pregnant
      women were enrolled in a randomized, placebo-controlled trial of intermittent
      preventive treatment with sulfadoxine-pyrimethamine, and their infants were
      followed up throughout infancy. Overall mortality and malaria morbidity rates
      were recorded. The association of maternal and fetal risk factors with infant
      mortality and malaria morbidity was assessed. RESULTS: There were 58 infant
      deaths among 997 live-born infants. The risk of dying during infancy was
      increased among infants born to women with acute placental infection (odds ratio
      [OR], 5.08 [95% confidence interval (CI), 1.77-14.53)], parasitemia in cord blood
      (OR, 19.31 [95% CI, 4.44-84.02]), low birth weight (OR, 2.82 [95% CI, 1.27-6.28])
      or prematurity (OR, 3.19 [95% CI, 1.14-8.95]). Infants born to women who had
      clinical malaria during pregnancy (OR, 1.96 [95% CI, 1.13-3.41]) or acute
      placental infection (OR, 4.63 [95% CI, 2.10-10.24]) had an increased risk of
      clinical malaria during infancy. CONCLUSIONS: Malaria infection at the end of
      pregnancy and maternal clinical malaria negatively impact survival and malaria
      morbidity in infancy. Effective clinical management and prevention of malaria in
      pregnancy may improve infant's health and survival.

PMID- 21199882
TI  - Impact of 2-dose vaccination on varicella epidemiology: Connecticut--2005-2008.
AB  - In 2006, the Advisory Committee on Immunization Practices recommended that
      children routinely receive 2 varicella vaccine doses in place of the 1 dose
      previously recommended. This recommendation's initial impact on varicella
      epidemiology in Connecticut was assessed. Reported incidence and case-specific
      data were compared for 2005 and 2008. Varicella incidence decreased from 48.7
      cases/100,000 persons in 2005 to 24.5 in 2008. Age-specific incidence decreased
      significantly (P < .05) among children aged 1-14 years. Reported varicella
      incidence has declined in Connecticut after implementation of routine 2-dose
      varicella vaccination for children. Continued surveillance is needed to determine
      the recommendation's full impact.

PMID- 21199883
TI  - Tissue inhibitor of matrix-metalloprotease-1 predicts risk of hepatic fibrosis in
      human Schistosoma japonicum infection.
AB  - BACKGROUND: Schistosomes infect 200 million individuals annually and cause
      significant hepatic fibrosis in up to 20%. Little is known regarding the
      mechanisms of schistosome-associated hepatic fibrosis in humans, and few
      biomarkers for risk of fibrosis have been identified. METHODS: We treated 611
      Schistosoma japonicum-infected Filipinos with praziquantel (PZQ) and performed
      ultrasound to quantify hepatic fibrosis at baseline and 12 months after PZQ
      treatment. We developed a multiplexed assay (FibroPlex) that quantifies
      predictors and effect modifiers of fibrosis. We measured FibroPlex analytes
      produced by peripheral blood mononuclear cells stimulated with schistosome egg
      antigen 4 weeks after PZQ treatment and related these levels to risk of fibrosis
      1 year after PZQ treatment. RESULTS: After adjusting for potential confounders,
      including baseline grade of fibrosis, individuals with detectable tissue
      inhibitor of matrix-metalloprotease-1 (TIMP-1) had a 3.5-fold greater risk of
      fibrosis 1 year after PZQ treatment, compared with individuals with undetectable
      levels (odds ratio, 3.48; 95% confidence interval, 1.41-8.43; P = .007).
      DISCUSSION: Because TIMP-1 inhibits most matrix metalloproteases, which are
      responsible for collagen degradation, these data suggest that schistosome
      associated hepatic fibrosis results, in part, from excessive inhibition of
      collagen remodeling. These data further suggest that TIMP-1 is a promising
      biomarker for assessing risk of hepatic fibrosis in schistosomiasis and,
      potentially, other infectious and noninfectious causes of liver disease.

PMID- 21199884
TI  - Pancreatic cancer treatment and research: an international expert panel
      discussion.
AB  - BACKGROUND: Pancreatic cancer has proven extremely challenging to treat. A
      collaborative effort is needed to advance research and improve treatment. An
      expert conference was conducted to elicit perspectives regarding the current
      treatment and future research of pancreatic cancer. METHODS: The conference
      comprised an international panel of experts representing five European countries
      and the United States. RESULTS: Adjuvant radiotherapy is used more frequently in
      the United States than in Europe. In locally advanced disease, there is now more
      emphasis on early chemotherapy in both Europe and the United States. In
      metastatic disease, combination chemotherapy is commonly used in Europe and the
      United States. This varies by country. Advancing pancreatic research will require
      improving biorepositories and developing a roadmap to prioritize therapeutic
      targets in different models. Small randomized phase II trials of both non
      selected and enriched patient populations will help identify activity of new
      agents. Phase III trials should only be initiated in appropriate patients based
      on strong clinical and biological signals. Developing drugs in the adjuvant
      setting may be preferable to eliminate some of the challenges of drug development
      in the advanced disease setting. CONCLUSION: Progress in research combined with
      encouraging improvements from the past offer hope for the future of pancreatic
      cancer patients.

PMID- 21199885
TI  - CD5-positive diffuse large B-cell lymphoma: a retrospective study in 337 patients
      treated by chemotherapy with or without rituximab.
AB  - BACKGROUND: CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) shows poor
      prognosis and frequent central nervous system (CNS) relapses under anthracycline
      containing chemotherapy. The aim of this study was to determine the prognosis and
      CNS relapse incidence of CD5+ DLBCL in the rituximab era. PATIENTS AND METHODS:
      We analyzed 337 patients with CD5+ DLBCL who received chemotherapy with (R
      chemotherapy group; n = 184) or without (chemotherapy group; n = 153) rituximab.
      RESULTS: No significant difference was found in clinical background comparisons
      between the two groups. In the R-chemotherapy group, 60% of the patients were
      older than 65 years at diagnosis. Both the complete response rate and overall
      survival (OS) were significantly better in the R-chemotherapy group (P = 0.0003
      and P = 0.002, respectively). Multivariate analysis confirmed that chemotherapy
      without rituximab was associated with unfavorable OS. However, the probability of
      CNS relapse did not differ between the two groups (P = 0.89). The CNS relapse was
      strongly associated with short OS (P < 0.0001). In the R-chemotherapy group, 83%
      of patients who experienced CNS relapse had parenchymal disease. CONCLUSIONS: Our
      results indicate that rituximab improves the OS of patients with CD5+ DLBCL but
      does not decrease the CNS relapse rate. More effective treatments with CNS
      prophylaxis are needed for CD5+ DLBCL patients.

PMID- 21199886
TI  - Identification of a serum-detectable metabolomic fingerprint potentially
      correlated with the presence of micrometastatic disease in early breast cancer
      patients at varying risks of disease relapse by traditional prognostic methods.
AB  - BACKGROUND: Prognostic tools in early breast cancer are inadequate. The evolving
      field of metabolomics may allow more accurate identification of patients with
      residual micrometastases. PATIENTS AND METHODS: Forty-four early breast cancer
      patients with pre- and postoperative serum samples had metabolomic assessment by
      nuclear magnetic resonance. Fifty-one metastatic patients served as control.
      Differential clustering was identified and used to calculate individual early
      patient 'metabolomic risk', calculated as inverse distance of each early patient
      from the metastatic cluster barycenter. Metabolomic risk was compared with
      Adjuvantionline 10-year mortality assessment. RESULTS: Innate serum metabolomic
      differences exist between early and metastatic patients. Preoperative patients
      were identified with 75% sensitivity, 69% specificity and 72% predictive
      accuracy. Comparison with Adjuvantionline revealed discordance. Of 21 patients
      assessed as high risk by Adjuvantionline, 10 (48%) and 6 (29%) were at high risk
      by metabolomics in pre- and postoperative settings, respectively. Of 23 low-risk
      patients by Adjuvantionline, 11 (48%) preoperative and 20 (87%) postoperative
      patients were at low risk by metabolomics. CONCLUSIONS: This study identifies
      metabolomic discrimination between early and metastatic breast cancer.
      Micrometastatic disease may account for metabolomic misclassification of some
      early patients as metastatic. Metabolomics identifies more patients as low
      relapse risk compared with Adjuvantionline. Further exploration of this
      metabolomic fingerprint is warranted.

PMID- 21199887
TI  - Artificial nutrition and hydration in the last week of life in cancer patients. A
      systematic literature review of practices and effects.
AB  - BACKGROUND: The benefits and burdens of artificial nutrition (AN) and artificial
      hydration (AH) in end-of-life care are unclear. We carried out a literature
      review on the use of AN and AH in the last days of life of cancer patients.
      MATERIALS AND METHODS: We systematically searched for papers in PubMed, CINAHL,
      PsycInfo and EMBASE. All English papers published between January 1998 and July
      2009 that contained data on frequencies or effects of AN or AH in cancer patients
      in the last days of life were included. RESULTS: Reported percentages of patients
      receiving AN or AH in the last week of life varied from 3% to 53% and from 12% to
      88%, respectively. Five studies reported on the effects of AH: two found positive
      effects (less chronic nausea, less physical dehydration signs), two found
      negative effects (more ascites, more intestinal drainage) and four found also no
      effects on terminal delirium, thirst, chronic nausea and fluid overload. No study
      reported on the sole effect of AN. CONCLUSIONS: Providing AN or AH to cancer
      patients who are in the last week of life is a frequent practice. The effects on
      comfort, symptoms and length of survival seem limited. Further research will
      contribute to better understanding of this important topic in end-of-life care.

PMID- 21199888
TI  - Changes over time in socioeconomic inequalities in breast and rectal cancer
      survival in England and Wales during a 32-year period (1973-2004): the potential
      role of health care.
AB  - BACKGROUND: Socioeconomic inequalities in cancer survival are well documented but
      they vary for different cancers and over time. Reasons for these differences are
      poorly understood. PATIENTS AND METHODS: For England and Wales, we examined
      trends in socioeconomic survival inequalities for breast cancer in women and
      rectal cancer in men during the 32-year period 1973-2004. We used a theoretical
      framework based on Victora's 'inverse equity' law, under which survival
      inequalities could change with the advent of successive new treatments, of
      varying effectiveness, which are disseminated with different speed among patients
      of different socioeconomic groups. We estimated 5-year relative survival for
      patients of different deprivation quintiles and examined trends in survival
      inequalities in light of major treatment innovations. RESULTS: Inequalities in
      breast cancer survival (921,611 cases) narrowed steadily during the study (from 
      10% to -6%). In contrast, inequalities in rectal cancer survival (187,104 cases)
      widened overall (form -5% to -11%) with fluctuating periods of narrowing
      inequality. CONCLUSIONS: Trends in socioeconomic differences in tumour or patient
      factors are unlikely explanations of observed changes over time in survival
      inequalities. The sequential introduction into clinical practice of new
      treatments of progressively smaller incremental benefit may partly explain the
      reduction in inequality in breast cancer survival.

PMID- 21199889
TI  - The role for the exocyst complex subunits Exo70B2 and Exo70H1 in the plant
      pathogen interaction.
AB  - Recently, the octameric vesicle-tethering complex exocyst was found in plants and
      its importance for Arabidopsis morphogenesis was demonstrated. Exo70 exocyst
      subunits in plants, unlike in yeasts and mammals, are represented by a multigene
      family, comprising 23 members in Arabidopsis. For Exo70B2 and Exo70H1 paralogues,
      transcriptional up-regulation was confirmed on treatment with an elicitor
      peptide, elf18, derived from the bacterial elongation factor. Their ability to
      participate in the exocyst complex formation was inferred by the interaction of
      both the Exo70s with several other exocyst subunits using the yeast two-hybrid
      system. Arabidopsis plants mutated in these two genes were used to analyse their
      local reaction upon inoculation with Pseudomonas syringae pv. maculicola and the
      fungal pathogen Blumeria graminis f. sp. hordei. The Pseudomonas sensitivity test
      revealed enhanced susceptibility for the two exo70B2 and one H1 mutant lines.
      After Blumeria inoculation, an increase in the proportion of abnormal papilla
      formation, with an unusual wide halo made of vesicle-like structures, was found
      in exo70B2 mutants. Intracellular localization of both Exo70 proteins was studied
      following a GFP fusion assay and Agrobacterium-mediated transient expression of
      the constructs in Nicotiana benthamiana leaf epidermis. GFP-Exo70H1 localizes in
      the vesicle-like structures, while GFP-Exo70B2 is localized mainly in the
      cytoplasm. It is concluded that both Exo70B2 and Exo70H1 are involved in the
      response to pathogens, with Exo70B2 having a more important role in cell wall
      apposition formation related to plant defence.

PMID- 21199891
TI  - A particular diffusion model for incomplete longitudinal data: application to the
      multicenter AIDS cohort study.
AB  - Longitudinal studies, in which individuals are measured repeatedly in time, are
      often incomplete. We model continuous-time longitudinal data from the Multicenter
      AIDS Cohort Study using a diffusion model in which the diffusion parameters are
      functions of the covariates. These data are jointly modeled with the process of
      time-to-death due to AIDS. We show that, even for large data sets with a large
      number of missing variables, a Bayesian analysis is feasible using Gibbs sampling
      and compare a complete case analysis with a Bayesian treatment of missing values.

PMID- 21199890
TI  - Functional characterization of the three genes encoding 1-deoxy-D-xylulose 5
      phosphate synthase in maize.
AB  - The 1-deoxy-D-xylulose 5-phosphate synthase (DXS) enzyme catalyses the first
      biosynthetic step of the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. In
      plants the MEP pathway is involved in the synthesis of the common precursors to
      the plastidic isoprenoids, isopentenyl diphosphate and dimethylallyl diphosphate,
      in plastids. DXS is recognized as limiting this pathway and is a potential target
      for manipulation to increase various isoprenoids such as carotenoids. In Zea mays
      three dxs genes exist that encode plastid-targeted functional enzymes. Evidence
      is provided that these genes represent phylogenetically distinctive clades
      conserved among plants preceding monocot-dicot divergence. There is differential
      accumulation for each dxs gene transcript, during development and in response to
      external signals such as light. At the protein level, the analysis demonstrates
      that in Z. mays, DXS protein is feedback regulated in response to the inhibition
      of the pathway flow. The results support that the multilevel regulation of DXS
      activity is conserved in evolution.

PMID- 21199892
TI  - Demographic signatures accompanying the evolution of selfing in Leavenworthia
      alabamica.
AB  - The evolution of selfing from outcrossing is a common transition, yet little is
      known about the mutations and selective factors that promote this shift. In the
      mustard family, single-locus self-incompatibility (SI) enforces outcrossing. In
      this study, we test whether mutations causing self-compatibility (SC) are linked
      to the self-incompatibility locus (S-locus) in Leavenworthia alabamica, a species
      where two selfing races (a2 and a4) co-occur with outcrossing populations. We
      also infer the ecological circumstances associated with origins of selfing using
      molecular sequence data. Genealogical reconstruction of the Lal2 locus, the
      putative ortholog of the SRK locus, showed that both selfing races are fixed for
      one of two different S-linked Lal2 sequences, whereas outcrossing populations
      harbor many S-alleles. Hybrid crosses demonstrated that S-linked mutations cause
      SC in each selfing race. These results strongly suggest two origins of selfing in
      this species, a result supported by population admixture analysis of 16
      microsatellite loci and by a population tree built from eight nuclear loci. One
      selfing race (a4) shows signs of a severe population bottleneck, suggesting that
      reproductive assurance might have caused the evolution of selfing in this case.
      In contrast, the population size of race a2 cannot be distinguished from that of
      outcrossing populations after correcting for differences in selfing rates.
      Coalescent-based analyses suggest a relatively old origin of selfing in the a4
      race (~150 ka ago), whereas selfing evolved recently in the a2 race (~12-48 ka
      ago). These results imply that S-locus mutations have triggered two recent shifts
      to selfing in L. alabamica, but that these transitions are not always associated
      with a severe population bottleneck, suggesting that factors other than
      reproductive assurance may play a role in its evolution.

PMID- 21199893
TI  - Polymorphism, divergence, and the role of recombination in Saccharomyces
      cerevisiae genome evolution.
AB  - A contentious issue in molecular evolution and population genetics concerns the
      roles of recombination as a facilitator of natural selection and as a potential
      source of mutational input into genomes. The budding yeast Saccharomyces
      cerevisiae, in particular, has injected both insights and confusion into this
      topic, as an early system subject to genomic analysis with subsequent conflicting
      reports. Here, we revisit the role of recombination in mutation and selection
      with recent genome-wide maps of population polymorphism and recombination for S.
      cerevisiae. We confirm that recombination-associated mutation does not leave a
      genomic signature in yeast and conclude that a previously observed, enigmatic,
      negative recombination-divergence correlation is largely a consequence of weak
      selection and other genomic covariates. We also corroborate the presence of
      biased gene conversion from patterns of polymorphism. Moreover, we identify
      significant positive relations between recombination and population polymorphism
      at putatively neutrally evolving sites, independent of other factors and the
      genomic scale of interrogation. We conclude that widespread natural selection
      across the yeast genome has left its imprint on segregating genetic variation,
      but that this signature is much weaker than in Drosophila and Caenorhabditis.

PMID- 21199894
TI  - Distorted object perception following whole-field adaptation of saccadic eye
      movements.
AB  - The adaptation of an observer's saccadic eye movements to artificial post
      saccadic visual error can lead to perceptual mislocalization of individual,
      transient visual stimuli. In this study, we demonstrate that simultaneous
      saccadic adaptation to a consistent error pattern across a large number of
      saccade vectors is accompanied by corresponding spatial distortions in the
      perception of persistent objects. To induce this adaptation, we artificially
      introduced several post-saccadic error patterns, which led to a systematic
      distortion in participants' oculomotor space and a corresponding distortion in
      their perception of the relative dimensions of a cross-figure. The results
      indicate a tight coupling between the oculomotor and visual-perceptual spaces
      that is not limited to misperception of individual visual locations but also
      affects metrics in the visual-perceptual space. This coupling suggests that our
      visual perception is continuously recalibrated by the post-saccadic error signal.

PMID- 21199895
TI  - Sex-specific norms code face identity.
AB  - Face identity aftereffects suggest that an average face, which is continuously
      updated by experience, functions as a norm for coding identity. Sex-contingent
      figural face aftereffects indicate that different norms are maintained for male
      and female faces but do not directly implicate them in coding identity. Here, we
      investigated whether sex-specific norms are used to code the identities of male
      and female faces or whether a generic, androgynous norm is used for all faces. We
      measured identity aftereffects for adapt-test pairs that were opposite relative
      to a sex-specific average and pairs that were opposite relative to an androgynous
      average. Identity aftereffects are generally larger for adapt-test pairs that lie
      opposite an average face, which functions as a norm for coding identity, than
      those that do not. Therefore, we reasoned that whichever average gives the larger
      aftereffect would be closer to the true psychological norm. Aftereffects were
      substantially and significantly larger for pairs that lie opposite a sex-specific
      than an androgynous average. This difference remained significant after
      correcting for differences in test trajectory length. These results indicate
      that, despite the common structure shared by all faces, identity is coded using
      sex-specific norms. We suggest that the use of category-specific norms may
      increase coding efficiency and help us discriminate thousands of faces despite
      their similarity as patterns.

PMID- 21199896
TI  - IFN-gamma attenuates hypoxia-inducible factor (HIF) activity in intestinal
      epithelial cells through transcriptional repression of HIF-1beta.
AB  - Numerous studies have revealed that hypoxia and inflammation occur coincidentally
      in mucosal disorders, such as inflammatory bowel disease. During inflammation,
      epithelial-expressed hypoxia-inducible factor (HIF) serves an endogenously
      protective function. In this study, we sought to explore how mucosal immune
      responses influence HIF-dependent end points. Guided by a screen of relevant
      inflammatory mediators, we identified IFN-gamma as a potent repressor of HIF
      dependent transcription in human intestinal epithelial cells. Analysis of HIF
      levels revealed that HIF-1beta, but not HIF-1alpha, is selectively repressed by
      IFN-gamma in a JAK-dependent manner. Cloning and functional analysis of the HIF
      1beta promoter identified a prominent region for IFN-gamma-dependent repression.
      Further studies revealed that colonic IFN-gamma and HIF-1beta levels were
      inversely correlated in a murine colitis model. Taken together, these studies
      demonstrated that intestinal epithelial HIF is attenuated by IFN-gamma through
      transcriptional repression of HIF-1beta. These observations are relevant to the
      pathophysiology of colitis (i.e., that loss of HIF signaling during active
      inflammation may exacerbate disease pathogenesis).

PMID- 21199897
TI  - Cutting edge: TIGIT has T cell-intrinsic inhibitory functions.
AB  - Costimulatory molecules regulate the functional outcome of T cell activation, and
      disturbance of the balance between activating and inhibitory signals results in
      increased susceptibility to infection or the induction of autoimmunity. Similar
      to the well-characterized CD28/CTLA-4 costimulatory pathway, a newly emerging
      pathway consisting of CD226 and T cell Ig and ITIM domain (TIGIT) has been
      associated with susceptibility to multiple autoimmune diseases. In this study, we
      examined the role of the putative coinhibitory molecule TIGIT and show that loss
      of TIGIT in mice results in hyperproliferative T cell responses and increased
      susceptibility to autoimmunity. TIGIT is thought to indirectly inhibit T cell
      responses by the induction of tolerogenic dendritic cells. By generating an
      agonistic anti-TIGIT Ab, we demonstrate that TIGIT can inhibit T cell responses
      directly independent of APCs. Microarray analysis of T cells stimulated with
      agonistic anti-TIGIT Ab revealed that TIGIT can act directly on T cells by
      attenuating TCR-driven activation signals.

PMID- 21199898
TI  - IL-1beta is overexpressed and aberrantly regulated in corticosteroid
      nonresponders with autoimmune inner ear disease.
AB  - Autoimmune inner ear disease is an enigmatic disorder characterized by recurring
      episodes of sudden or progressive sensorineural hearing loss. Hearing loss can be
      improved by timely corticosteroid administration, but only half of those treated
      respond, and for many responders, that response is lost over time. The mechanisms
      that control corticosteroid responsiveness in this disorder are largely
      uncharacterized. We have previously identified that the induction by
      dexamethasone of IL-1R type II (IL-1R2) expression in PBMC predicts
      corticosteroid responsiveness in this disorder. In this study, we asked whether
      IL-1beta was overexpressed, and whether clinical corticosteroid responders
      differentially regulated IL-1beta expression or release in response to
      dexamethasone, as compared with nonresponders. IL-1beta has been reported to
      induce matrix metalloproteinase-9 (MMP-9) expression. Given that
      metalloproteinases can cleave IL-1R2, we also asked whether MMP-9 expression was
      altered in this disorder. In this study, we demonstrate that corticosteroid
      nonresponders have elevated plasma levels of IL-1beta and MMP-9 as compared with
      clinically responsive patients (p = 0.0008 and p = 0.037, respectively).
      Increasing MMP-9 expression correlated with increasing IL-1beta concentration,
      suggesting that IL-1beta expression regulates MMP-9 expression. As expected,
      monocytes were the predominant producers of IL-1beta. In vitro exposure of PBMC
      to dexamethasone from clinical corticosteroid responders suppressed IL-1beta
      release. PBMC of corticosteroid nonresponders have substantially higher release
      of IL-1beta into the conditioned media, and when exposed to dexamethasone, failed
      to repress IL-1beta release (p = 0.05). Treatment of PBMC from clinical
      corticosteroid nonresponders with anakinra resulted in repression of IL-1beta
      release, suggesting that IL-1beta blockade may be a viable therapy for these
      patients.

PMID- 21199899
TI  - A unique role of the cholera toxin A1-DD adjuvant for long-term plasma and memory
      B cell development.
AB  - Adjuvants have traditionally been appreciated for their immunoenhancing effects,
      whereas their impact on immunological memory has largely been neglected. In this
      paper, we have compared three mechanistically distinct adjuvants: aluminum salts
      (Alum), Ribi (monophosphoryl lipid A), and the cholera toxin A1 fusion protein
      CTA1-DD. Their influence on long-term memory development was dramatically
      different. Whereas a single immunization i.p. with 4-hydroxy-3-nitrophenyl acetyl
      (NP)-chicken gamma-globulin and adjuvant stimulated serum anti-NP IgG titers that
      were comparable at 5 wk, CTA1-DD-adjuvanted responses were maintained for >16 mo
      with a half-life of anti-NP IgG ~36 wk, but <15 wk after Ribi or Alum. A CTA1-DD
      dose-dependent increase in germinal center (GC) size and numbers was found, with
      >60% of splenic B cell follicles hosting GC at an optimal CTA1-DD dose. Roughly
      7% of these GC were NP specific. This GC-promoting effect correlated well with
      the persistence of long-term plasma cells in the bone marrow and memory B cells
      in the spleen. CTA1-DD also facilitated increased somatic hypermutation and
      affinity maturation of NP-specific IgG Abs in a dose-dependent fashion, hence
      arguing that large GC not only promotes higher Ab titers but also high-quality Ab
      production. Adoptive transfer of splenic CD80(+), but not CD80(-), B cells, at 1
      y after immunization demonstrated functional long-term anti-NP IgG and IgM memory
      cells. To our knowledge, this is the first report to specifically compare and
      document that adjuvants can differ considerably in their support of long-term
      immune responses. Differential effects on the GC reaction appear to be the basis
      for these differences.

PMID- 21199902
TI  - Managing bloodstream infections in patients who have short-term central venous
      catheters.
AB  - Catheter-related bloodstream infections can be complicated to manage, but a
      growing body of evidence supports specific recommendations. In 2009, the
      Infectious Diseases Society of America published updated guidelines for the
      diagnosis and management of all intravascular catheter-related infections. Here
      we provide a focused review on the management of bloodstream infections in adult
      patients with short-term (not surgically implanted and not tunneled) central
      venous catheters, including peripherally inserted central catheters. This review
      should serve as a ready reference for providers (eg, hospitalists, surgeons,
      physician assistants, nurse practitioners, intensivists) managing adult patients
      with short-term central venous catheters in place.

PMID- 21199900
TI  - Endothelial ICAM-1 protein induction is regulated by cytosolic phospholipase
      A2alpha via both NF-kappaB and CREB transcription factors.
AB  - The regulated expression of ICAM-1 plays an important role in inflammatory
      processes and immune responses. The present study aimed to determine the in vivo
      involvement of cytosolic phospholipase A(2)alpha (cPLA(2)alpha) in ICAM-1
      overexpression during inflammation and to elucidate the cPLA(2)alpha-specific
      role in signal events leading to ICAM-1 upregulation in endothelial cells.
      cPLA(2)alpha and ICAM-1 upregulation were detected in inflamed paws of mice with
      collagen-induced arthritis and in periepididymal adipose tissue of mice fed a
      high-fat diet. Intravenous injection of 2 mg/kg oligonucleotide antisense against
      cPLA(2)alpha (AS) that reduced cPLA(2)alpha upregulation also decreased ICAM-1
      overexpression, suggesting a key role of cPLA(2)alpha in ICAM-1 upregulation
      during inflammation. Preincubation of endothelial ECV-304 cells that express ICAM
      1 and of HUVEC that express ICAM-1 and VCAM-1 with 1 MUM AS prevented
      cPLA(2)alpha and the adhesion molecule upregulation induced by TNF-alpha and
      inhibited their adherence to phagocyte like-PLB cells. Whereas AS did not inhibit
      NADPH oxidase 4-NADPH oxidase activity, inhibition of oxidase activity attenuated
      cPLA(2)alpha activation, suggesting that NADPH oxidase acts upstream to
      cPLA(2)alpha. Attenuating cPLA(2)alpha activation by AS or diphenylene iodonium
      prevented the induction of cyclooxygenase-2 and the production of PGE(2) that
      were essential for ICAM-1 upregulation. Inhibition of cPLA(2)alpha activity by AS
      inhibited the phosphorylation of both p65 NF-kappaB on Ser(536) and protein
      kinase A-dependent CREB. To our knowledge, our results are the first to show that
      CREB activation is involved in ICAM-1 upregulation and suggest that cPLA(2)alpha
      activated by NADPH oxidase is required for sequential phosphorylation of NF
      kappaB by an undefined kinase and CREB activation by PGE(2)-mediated protein
      kinase A.

PMID- 21199903
TI  - To better manage cancer symptoms.

PMID- 21199904
TI  - Symptom management: an important part of cancer care.
AB  - Physicians can do a better job of palliating symptoms and improving the quality
      of life of cancer patients if they understand the principles of symptom
      management. We review the general principles of symptom management for fatigue,
      anorexia, constipation, dyspnea, nausea, and vomiting.

PMID- 21199905
TI  - Q: Do patients with prosthetic joints require dental antimicrobial prophylaxis?

PMID- 21199906
TI  - Proton pump inhibitor side effects and drug interactions: much ado about nothing?
AB  - Proton pump inhibitors (PPIs) are widely prescribed for acid-peptic disease. In
      general, the safety of this class of drugs has been excellent. However, in the
      past several years, epidemiologic studies have indicated possible risks that are
      biologically plausible.

PMID- 21199907
TI  - Premenopausal osteoporosis, an overlooked consequence of anorexia nervosa.
AB  - Many young women with anorexia nervosa develop premenopausal osteoporosis. In
      particular, female athletes have a much higher incidence of disordered eating
      than their peers and therefore are at a much higher risk of stress fractures and
      other traumatic bone pathology. This review summarizes factors affecting the
      development of premenopausal osteoporosis in these patients and identifies
      potential targets for intervention.

PMID- 21199908
TI  - A 31-year-old man with abdominal pain and a rectal nodule.

PMID- 21199909
TI  - Genotype is correlated with but does not predict virulence of Vibrio vulnificus
      biotype 1 in subcutaneously inoculated, iron dextran-treated mice.
AB  - Vibrio vulnificus is the leading cause of reported deaths from infections related
      to consumption of seafood in the United States. Affected predisposed individuals
      frequently die rapidly from sepsis. Otherwise healthy people can experience
      severe wound infection, which can lead to sepsis and death. A question is why,
      with so many people consuming contaminated raw oysters, the incidence of severe
      V. vulnificus disease is low. Molecular typing systems have shown associations of
      V. vulnificus genotypes and the environmental or clinical source of the strains,
      suggesting that different genotypes possess different virulence potentials. We
      examined 69 V. vulnificus biotype 1 strains that were genotyped by several
      methods and evaluated them for virulence in a subcutaneously inoculated iron
      dextran-treated mouse model. By examining the relationships between skin
      infection, systemic liver infection, and presumptive death (a decrease in body
      temperature), we determined that liver infection is predicated on severe skin
      infection and that death requires significant liver infection. Although most
      strains caused severe skin infection, not every strain caused systemic infection
      and death. Strains with polymorphisms at multiple loci (rrn, vcg, housekeeping
      genes, and repetitive DNA) designated profile 2 were more likely to cause lethal
      systemic infection with more severe indicators of virulence than were profile 1
      strains with different polymorphisms at these loci. However, some profile 1
      strains were lethal and some profile 2 strains did not cause systemic infection.
      Therefore, current genotyping schemes cannot strictly predict the virulence of V.
      vulnificus strains and further investigation is needed to identify virulence
      genes as markers of virulence.

PMID- 21199910
TI  - Toll-like receptor 2 activation by Chlamydia trachomatis is plasmid dependent,
      and plasmid-responsive chromosomal loci are coordinately regulated in response to
      glucose limitation by C. trachomatis but not by C. muridarum.
AB  - We previously demonstrated that plasmid-deficient Chlamydia muridarum retains the
      ability to infect the murine genital tract but does not elicit oviduct pathology
      because it fails to activate Toll-like receptor 2 (TLR2). We derived a plasmid
      cured derivative of the human genital isolate Chlamydia trachomatis D/UW-3/Cx,
      strain CTD153, which also fails to activate TLR2, indicating this virulence
      phenotype is associated with plasmid loss in both C. trachomatis and C.
      muridarum. As observed with plasmid-deficient C. muridarum, CTD153 displayed
      impaired accumulation of glycogen within inclusions. Transcriptional profiling of
      the plasmid-deficient strains by using custom microarrays identified a conserved
      group of chromosomal loci, the expression of which was similarly controlled in
      plasmid-deficient C. muridarum strains CM972 and CM3.1 and plasmid-deficient C.
      trachomatis CTD153. However, although expression of glycogen synthase, encoded by
      glgA, was greatly reduced in CTD153, it was unaltered in plasmid-deficient C.
      muridarum strains. Thus, additional plasmid-associated factors are required for
      glycogen accumulation by this chlamydial species. Furthermore, in C. trachomatis,
      glgA and other plasmid-responsive chromosomal loci (PRCLs) were transcriptionally
      responsive to glucose limitation, indicating that additional regulatory elements
      may be involved in the coordinated expression of these candidate virulence
      effectors. Glucose-limited C. trachomatis displayed reduced TLR2 stimulation in
      an in vitro assay. During human chlamydial infection, glucose limitation may
      decrease chlamydial virulence through its effects on plasmid-responsive
      chromosomal genes.

PMID- 21199911
TI  - Shiga toxin subtypes display dramatic differences in potency.
AB  - Purified Shiga toxin (Stx) alone is capable of producing systemic complications,
      including hemolytic-uremic syndrome (HUS), in animal models of disease. Stx
      includes two major antigenic forms (Stx1 and Stx2), with minor variants of Stx2
      (Stx2a to -h). Stx2a is more potent than Stx1. Epidemiologic studies suggest that
      Stx2 subtypes also differ in potency, but these differences have not been well
      documented for purified toxin. The relative potencies of five purified Stx2
      subtypes, Stx2a, Stx2b, Stx2c, Stx2d, and activated (elastase-cleaved) Stx2d,
      were studied in vitro by examining protein synthesis inhibition using Vero monkey
      kidney cells and inhibition of metabolic activity (reduction of resazurin to
      fluorescent resorufin) using primary human renal proximal tubule epithelial cells
      (RPTECs). In both RPTECs and Vero cells, Stx2a, Stx2d, and elastase-cleaved Stx2d
      were at least 25 times more potent than Stx2b and Stx2c. In vivo potency in mice
      was also assessed. Stx2b and Stx2c had potencies similar to that of Stx1, while
      Stx2a, Stx2d, and elastase-cleaved Stx2d were 40 to 400 times more potent than
      Stx1.

PMID- 21199912
TI  - TcsL is an essential virulence factor in Clostridium sordellii ATCC 9714.
AB  - Clostridium sordellii is an important pathogen of humans and animals, causing a
      range of diseases, including myonecrosis, sepsis, and shock. Although relatively
      rare in humans, the incidence of disease is increasing, and it is associated with
      high mortality rates, approaching 70%. Currently, very little is known about the
      pathogenesis of C. sordellii infections or disease. Previous work suggested that
      the lethal large clostridial glucosylating toxin TcsL is the major virulence
      factor, but a lack of genetic tools has hindered our ability to conclusively
      assign a role for TcsL or, indeed, any of the other putative virulence factors
      produced by this organism. In this study, we have developed methods for the
      introduction of plasmids into C. sordellii using RP4-mediated conjugation from
      Escherichia coli and have successfully used these techniques to insertionally
      inactivate the tcsL gene in the reference strain ATCC 9714, using targetron
      technology. Virulence testing revealed that the production of TcsL is essential
      for the development of lethal infections by C. sordellii ATCC 9714 and also
      contributes significantly to edema seen during uterine infection. This study
      represents the first definitive identification of a virulence factor in C.
      sordellii and opens the way for in-depth studies of this important human pathogen
      at the molecular level.

PMID- 21199913
TI  - Dispensability of surfactant proteins A and D in immune control of Mycobacterium
      tuberculosis infection following aerosol challenge of mice.
AB  - Surfactant proteins A and D (SP-A and -D) play a role in many acute bacterial,
      viral, and fungal infections and in acute allergic responses. In vitro, human SPs
      bind Mycobacterium tuberculosis and alter human and rat macrophage-mediated
      functions. Here we report the roles of SP-A and SP-D in M. tuberculosis infection
      following aerosol challenge of SP-A-, SP-D-, and SP-A/-D-deficient mice. These
      studies surprisingly identified no gross defects in uptake or immune control of
      M. tuberculosis in SP-A-, SP-D-, and SP-A/-D-deficient mice. While both SP-A- and
      SP-D-deficient mice exhibited evidence of immunopathologic defects, the
      CD11b(high) CD11c(high) dendritic cell populations and the gamma interferon (IFN
      gamma)-dependent CD4(+) T cell response to M. tuberculosis were unaltered in all
      genotypes tested. Together, these data indicate that SP-A and SP-D are
      dispensable for immune control of M. tuberculosis in a low-dose, aerosol
      challenge, murine model of tuberculosis (TB).

PMID- 21199914
TI  - Few physicians prescribe 5-alpha reductase inhibitors for prostate cancer
      prevention.

PMID- 21199915
TI  - Elimination of cancer disparities via organizational transformation and community
      driven approaches.

PMID- 21199916
TI  - Patients with nonovarian peritoneal carcinomatosis achieve long-term survival.

PMID- 21199917
TI  - Sirtuin-1 targeting promotes Foxp3+ T-regulatory cell function and prolongs
      allograft survival.
AB  - Sirtuin 1 (Sirt1), a class III histone/protein deacetylase, is central to
      cellular metabolism, stress responses, and aging, but its contributions to
      various host immune functions have been little investigated. To study the role of
      Sirt1 in T cell functions, we undertook targeted deletions by mating mice with a
      floxed Sirt1 gene to mice expressing CD4-cre or Foxp3-cre recombinase,
      respectively. We found that Sirt1 deletion left conventional T-effector cell
      activation, proliferation, and cytokine production largely unaltered. However,
      Sirt1 targeting promoted the expression of Foxp3, a key transcription factor in T
      regulatory (Treg) cells, and increased Treg suppressive functions in vitro and in
      vivo. Consistent with these data, mice with targeted deletions of Sirt1 in either
      CD4(+) T cells or Foxp3(+) Treg cells exhibited prolonged survival of major
      histocompatibility complex (MHC)-mismatched cardiac allografts. Allografts in
      Sirt1-targeted recipients showed long-term preservation of myocardial histology
      and infiltration by Foxp3(+) Treg cells. Comparable results were seen in wild
      type allograft recipients treated with Sirt1 inhibitors, such as EX-527 and
      splitomicin. Hence, Sirt1 may inhibit Treg functions, and its targeting may have
      therapeutic value in autoimmunity and transplantation.

PMID- 21199919
TI  - Protein interaction domain mapping of human kinetochore protein Blinkin reveals a
      consensus motif for binding of spindle assembly checkpoint proteins Bub1 and
      BubR1.
AB  - The kinetochore is a supramolecular structure essential for microtubule
      attachment and the mitotic checkpoint. Human blinkin/human Spc105 (hSpc105)/hKNL1
      was identified originally as a mixed-lineage leukemia (MLL) fusion partner and
      later as a kinetochore component. Blinkin directly binds to several structural
      and regulatory proteins, but the precise binding sites have not been defined.
      Here, we report distinct and essential binding domains for Bub1 and BubR1 (here
      designated Bubs) at the N terminus of blinkin and for Zwint-1 and hMis14/hNsl1 at
      the C terminus. The minimal binding sites for Bub1 and BubR1 are separate but
      contain a consensus KI motif, KI(D/N)XXXF(L/I)XXLK. RNA interference (RNAi)
      mediated replacement with mutant blinkin reveals that the Bubs-binding domain is
      functionally important for chromosome alignment and segregation. We also provide
      evidence that hMis14 mediates hNdc80 binding to blinkin at the kinetochore. The C
      terminal fragment of blinkin locates at kinetochores in a dominant-negative
      fashion by displacing endogenous blinkin from kinetochores. This negative
      dominance is relieved by mutations of the hMis14 binding PPSS motif on the C
      terminus of blinkin or by fusion of the N sequence that binds to Bub1 and BubR1.
      Taken together, these results indicate that blinkin functions to connect Bub1 and
      BubR1 with the hMis12, Ndc80, and Zwint-1 complexes, and disruption of this
      connection may lead to tumorigenesis.

PMID- 21199918
TI  - CtBP2 downregulation during neural crest specification induces expression of Mitf
      and REST, resulting in melanocyte differentiation and sympathoadrenal lineage
      suppression.
AB  - Trunk neural crest (NC) cells differentiate to neurons, melanocytes, and glia. In
      NC cultures, cyclic AMP (cAMP) induces melanocyte differentiation while
      suppressing the neuronal sympathoadrenal lineage, depending on the signal
      intensity. Melanocyte differentiation requires activation of CREB and cAMP
      dependent protein kinase A (PKA), but the role of PKA is not understood. We have
      demonstrated, in NC cultures, cAMP-induced transcription of the microphthalmia
      associated transcription factor gene (Mitf) and the RE-1 silencing transcription
      factor gene (REST), both Wnt-regulated genes. In NC cultures and zebrafish,
      knockdown of the corepressor of Wnt-mediated transcription C-terminal binding
      protein 2 (CtBP2) but not CtBP1 derepressed Mitf and REST expression and enhanced
      melanocyte differentiation. cAMP in NC and B16 melanoma cells decreased CtBP2
      protein levels, while inhibition of PKA or proteasome rescued CtBP2 degradation.
      Interestingly, knockdown of homeodomain-interacting protein kinase 2 (HIPK2), a
      CtBP stability modulator, increased CtBP2 levels, suppressed expression of Mitf,
      REST, and melanocyte differentiation, and increased neuronal gene expression and
      sympathoadrenal lineage differentiation. We conclude that cAMP/PKA via HIPK2
      promotes CtBP2 degradation, leading to Mitf and REST expression. Mitf induces
      melanocyte specification, and REST suppresses neuron-specific gene expression and
      the sympathoadrenal lineage. Our studies identify a novel role for REST in NC
      cell differentiation and suggest cross talk between cAMP and Wnt signaling in NC
      lineage specification.

PMID- 21199920
TI  - The ARID family transcription factor bright is required for both hematopoietic
      stem cell and B lineage development.
AB  - Bright/Arid3a has been characterized both as an activator of immunoglobulin heavy
      chain transcription and as a proto-oncogene. Although Bright expression is highly
      B lineage stage restricted in adult mice, its expression in the earliest
      identifiable hematopoietic stem cell (HSC) population suggests that Bright might
      have additional functions. We showed that >99% of Bright(-/-) embryos die at
      midgestation from failed hematopoiesis. Bright(-/-) embryonic day 12.5 (E12.5)
      fetal livers showed an increase in the expression of immature markers. Colony
      forming assays indicated that the hematopoietic potential of Bright(-/-) mice is
      markedly reduced. Rare survivors of lethality, which were not compensated by the
      closely related paralogue Bright-derived protein (Bdp)/Arid3b, suffered HSC
      deficits in their bone marrow as well as B lineage-intrinsic developmental and
      functional deficiencies in their peripheries. These include a reduction in a
      natural antibody, B-1 responses to phosphocholine, and selective T-dependent
      impairment of IgG1 class switching. Our results place Bright/Arid3a on a select
      list of transcriptional regulators required to program both HSC and lineage
      specific differentiation.

PMID- 21199921
TI  - Increased glycolytic ATP synthesis is associated with tafenoquine resistance in
      Leishmania major.
AB  - Tafenoquine (TFQ), an 8-aminoquinoline used to treat and prevent Plasmodium
      infections, could represent an alternative therapy for leishmaniasis. Indeed, TFQ
      has shown significant leishmanicidal activity both in vitro and in vivo, where it
      targets Leishmania mitochondria and activates a final apoptosis-like process. In
      order not to jeopardize the life span of this potential antileishmania drug, it
      is important to determine the likelihood that Leishmania will develop resistance
      to TFQ and the mechanisms of resistance induced. To address this issue, a TFQ
      resistant Leishmania major promastigote line (R4) was selected. This resistance,
      which is unstable in a drug-free medium (revertant line), was maintained in
      intramacrophage amastigote forms, and R4 promastigotes were found to be cross
      resistant to other 8-aminoquinolines. A decreased TFQ uptake, which is probably
      associated with an alkalinization of the intracellular pH rather than drug
      efflux, was observed for both the R4 and revertant lines. TFQ induces a decrease
      in ATP synthesis in all Leishmania lines, although total ATP levels were
      maintained at higher values in R4 parasites. In contrast, ATP synthesis by
      glycolysis was significantly increased in R4 parasites, whereas mitochondrial ATP
      synthesis was similar to that in wild-type parasites. We therefore conclude that
      increased glycolytic ATP synthesis is the main mechanism underlying TFQ
      resistance in Leishmania.

PMID- 21199922
TI  - Influence of continuous venovenous hemofiltration and continuous venovenous
      hemodiafiltration on the disposition of doripenem.
AB  - The pharmacokinetics, safety, and tolerability of a single 1-hour, 500-mg
      intravenous infusion of doripenem were assessed in dialysis-dependent subjects
      with stage 5 chronic kidney disease undergoing continuous renal replacement
      therapy (CRRT) via 12-hour continuous venovenous hemofiltration (CVVH) (n = 6) or
      continuous venovenous hemodiafiltration (CVVHDF) (n = 5). Healthy volunteers were
      also assessed (n = 12). Concentrations of doripenem and the primary metabolite
      doripenem-M-1 were measured in plasma and ultrafiltrate or
      ultrafiltrate/dialysate by a validated liquid chromatography-tandem mass
      spectrometry method. In dialysis-dependent subjects, levels of systemic exposure
      to doripenem and doripenem-M-1 were approximately 3- and 5-fold greater,
      respectively, than those in healthy subjects: for doripenem, 98 MUg.h/ml for CVVH
      and 77 MUg.h/ml for CVVHDF versus 32 MUg.h/ml for healthy subjects, and for
      doripenem-M-1, 24 MUg.h/ml for CVVH and 22 MUg.h/ml for CVVHDF versus 4.7
      MUg.h/ml for healthy subjects. The mean sieving coefficients and saturation
      coefficients were >0.67 for both doripenem and doripenem-M-1. During CVVH and
      CVVHDF, respectively, the percentages of administered doripenem dose removed were
      38% and 29%, and clearances of doripenem were 22 and 25 ml/min. Both CVVH and
      CVVHDF efficiently removed doripenem and doripenem-M-1. Despite significant
      removal of drug by CVVH and CVVHDF, a single 1-hour, 500-mg doripenem infusion
      produced significantly higher plasma concentrations of doripenem, higher systemic
      exposure (area under the plasma concentration-time curve from time zero to 12 h
      after the start of infusion [AUC(0-12)]), and longer half-life (t(1/2)) in
      subjects receiving CVVH or CVVHDF than in healthy volunteers. The recovery of
      drug in ultrafiltrate and ultrafiltrate/dialysate and the enhanced rate of
      reduction of plasma concentrations indicate that CVVH and CVVHDF significantly
      augmented residual total body clearance of doripenem in subjects receiving CRRT.
      Doripenem dosage regimens for patients receiving CRRT thus need to be adjusted.

PMID- 21199923
TI  - Nonthermal dielectric-barrier discharge plasma-induced inactivation involves
      oxidative DNA damage and membrane lipid peroxidation in Escherichia coli.
AB  - Oxidative stress leads to membrane lipid peroxidation, which yields products
      causing variable degrees of detrimental oxidative modifications in cells.
      Reactive oxygen species (ROS) are the key regulators in this process and induce
      lipid peroxidation in Escherichia coli. Application of nonthermal (cold) plasma
      is increasingly used for inactivation of surface contaminants. Recently, we
      reported a successful application of nonthermal plasma, using a floating
      electrode dielectric-barrier discharge (FE-DBD) technique for rapid inactivation
      of bacterial contaminants in normal atmospheric air (S. G. Joshi et al., Am. J.
      Infect. Control 38:293-301, 2010). In the present report, we demonstrate that FE
      DBD plasma-mediated inactivation involves membrane lipid peroxidation in E. coli.
      Dose-dependent ROS, such as singlet oxygen and hydrogen peroxide-like species
      generated during plasma-induced oxidative stress, were responsible for membrane
      lipid peroxidation, and ROS scavengers, such as alpha-tocopherol (vitamin E),
      were able to significantly inhibit the extent of lipid peroxidation and oxidative
      DNA damage. These findings indicate that this is a major mechanism involved in FE
      DBD plasma-mediated inactivation of bacteria.

PMID- 21199924
TI  - Antimicrobial resistance among invasive nontyphoidal Salmonella enterica isolates
      in the United States: National Antimicrobial Resistance Monitoring System, 1996
      to 2007.
AB  - Nontyphoidal salmonellae (NTS) are important causes of community-acquired
      bloodstream infection. We describe patterns of antimicrobial resistance among
      invasive NTS in the United States. We compared bloodstream NTS isolates with
      those from stool submitted to the National Antimicrobial Resistance Monitoring
      System (NARMS) from 1996 to 2007. We describe antimicrobial resistance among
      invasive strains by serogroup and serotype. Of the 19,302 NTS isolates, 17,804
      (92.2%) were from stool or blood. Of these, 1,050 (5.9%) were bloodstream
      isolates. The median ages (ranges) of patients with and without bacteremia were
      36 (<1 to 97) years and 20 (<1 to 105) years, respectively (P < 0.001). Males
      (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.06 to 1.38) and those
      >=65 years of age were at greater risk for invasive disease. Salmonella enterica
      serotypes Enteritidis, Typhimurium, and Heidelberg were the most common serotypes
      isolated from blood; S. enterica serotypes Dublin, Sandiego, and Schwarzengrund
      were associated with the greatest risk for bloodstream isolation. Of invasive
      isolates, 208 (19.8%) were resistant to ampicillin, 117 (11.1%) to
      chloramphenicol, and 26 (2.5%) to trimethoprim-sulfamethoxazole; 28 (2.7%)
      isolates were resistant to nalidixic acid and 26 (2.5%) to ceftriaxone.
      Antimicrobial resistance to traditional agents is common. However, the occurrence
      of nalidixic acid and ceftriaxone resistance among invasive NTS is cause for
      clinical and public health vigilance.

PMID- 21199925
TI  - First identification and characterization of an AdeABC-like efflux pump in
      Acinetobacter genomospecies 13TU.
AB  - Non-Acinetobacter baumannii spp. are emerging among clinical Acinetobacter
      isolates causing nosocomial infections, and some (such as genomospecies 13TU)
      appear to be multidrug resistant. The prevalence of non-Acinetobacter baumannii
      spp. in the hospital setting is likely understated due to poor identification
      techniques. We report the first identification of an AdeABC-type efflux pump in
      an Acinetobacter genomospecies 13TU clinical isolate, its contribution to
      multidrug resistance, and the coexistence of three Ade-type efflux pumps in this
      strain.

PMID- 21199926
TI  - Antimicrobial susceptibility of Brucella melitensis isolates in Peru.
AB  - Brucellosis is an important public health problem in Peru. We evaluated 48 human
      Brucella melitensis biotype 1 strains from Peru between 2000 and 2006. MICs of
      isolates to doxycycline, azithromycin, gentamicin, rifampin, ciprofloxacin, and
      trimethoprim-sulfamethoxazole were determined by the Etest method. All isolates
      were sensitive to tested drugs during the periods of testing. Relapses did not
      appear to be related to drug resistance.

PMID- 21199927
TI  - Desbutyl-lumefantrine is a metabolite of lumefantrine with potent in vitro
      antimalarial activity that may influence artemether-lumefantrine treatment
      outcome.
AB  - Desbutyl-lumefantrine (DBL) is a metabolite of lumefantrine. Preliminary data
      from Plasmodium falciparum field isolates show greater antimalarial potency than,
      and synergy with, the parent compound and synergy with artemisinin. In the
      present study, the in vitro activity and interactions of DBL were assessed from
      tritium-labeled hypoxanthine uptake in cultures of the laboratory-adapted strains
      3D7 (chloroquine sensitive) and W2mef (chloroquine resistant). The geometric mean
      50% inhibitory concentrations (IC(50)s) for DBL against 3D7 and W2mef were 9.0 nM
      (95% confidence interval, 5.7 to 14.4 nM) and 9.5 nM (95% confidence interval,
      7.5 to 11.9 nM), respectively, and those for lumefantrine were 65.2 nM (95%
      confidence interval, 42.3 to 100.8 nM) and 55.5 nM (95% confidence interval, 40.6
      to 75.7 nM), respectively. An isobolographic analysis of DBL and lumefantrine
      combinations showed no interaction in either laboratory-adapted strain but mild
      synergy between DBL and dihydroartemisinin (sums of the fractional inhibitory
      concentrations of 0.92 [95% confidence interval, 0.87 to 0.98] and 0.94 [95%
      confidence interval, 0.90 to 0.99] for 3D7 and W2mef, respectively). Using a
      validated ultra-high-performance liquid chromatography-tandem mass spectrometry
      assay and 94 day 7 samples from a previously reported intervention trial, the
      mean plasma DBL was 31.9 nM (range, 1.3 to 123.1 nM). Mean plasma DBL
      concentrations were lower in children who failed artemether-lumefantrine
      treatment than in those with an adequate clinical and parasitological response
      (ACPR) (P = 0.053 versus P > 0.22 for plasma lumefantrine and the plasma
      lumefantrine-to-DBL ratio, respectively). DBL is more potent than the parent
      compound and mildly synergistic with dihydroartemisinin. These properties and the
      relationship between day 7 plasma concentrations and the ACPR suggest that it
      could be a useful alternative to lumefantrine as a part of artemisinin
      combination therapy.

PMID- 21199928
TI  - Selective advantage of resistant strains at trace levels of antibiotics: a simple
      and ultrasensitive color test for detection of antibiotics and genotoxic agents.
AB  - Many studies have examined the evolution of bacterial mutants that are resistant
      to specific antibiotics, and many of these focus on concentrations at and above
      the MIC. Here we ask for the minimum concentration at which existing resistant
      mutants can outgrow sensitive wild-type strains in competition experiments at
      antibiotic levels significantly below the MIC, and we define a minimum selective
      concentration (MSC) in Escherichia coli for two antibiotics, which is near 1/5 of
      the MIC for ciprofloxacin and 1/20 of the MIC for tetracycline. Because of the
      prevalence of resistant mutants already in the human microbiome, allowable levels
      of antibiotics to which we are exposed should be below the MSC. Since this
      concentration often corresponds to low or trace levels of antibiotics, it is
      helpful to have simple tests to detect such trace levels. We describe a simple
      ultrasensitive test for detecting the presence of antibiotics and genotoxic
      agents. The test is based on the use of chromogenic proteins as color markers and
      the use of single and multiple mutants of Escherichia coli that have greatly
      increased sensitivity to either a wide range of antibiotics or specific
      antibiotics, antibiotic families, and genotoxic agents. This test can detect
      ciprofloxacin at 1/75 of the MIC.

PMID- 21199929
TI  - Paraoxonases as potential antibiofilm agents: their relationship with quorum
      sensing signals in Gram-negative bacteria.
AB  - The property of many bacteria to form biofilms constitutes a major health
      problem. Bacteria living in biofilms have a very high resistance to antibiotics.
      Biofilms may develop at a certain locations with the participation of secreted
      molecules, termed quorum-sensing signals, when a sufficient density of bacterial
      growth occurs. In Gram-negative bacteria, acyl homoserine lactones (AHL) have
      been identified as major quorum-sensing signals. The paraoxonases (PONs)
      constitute a family of enzymes comprising 3 members (PON1, PON2, and PON3) that
      have lactonase activity and are able to hydrolyze AHL. In this minireview, we
      summarize some existing basic knowledge on PON genetics, biochemistry, and
      function and describe recent research that reports evidence of the important
      roles that they may play in the organism's defense against biofilm formation.
      Finally, we propose some lines of future research that could be very productive.

PMID- 21199930
TI  - Dextromethorphan efficiently increases bactericidal activity, attenuates
      inflammatory responses, and prevents group a streptococcal sepsis.
AB  - Group A streptococcus (GAS) is an important human pathogen that causes a wide
      spectrum of diseases, ranging from mild throat and skin infections to severe
      invasive diseases such as necrotizing fasciitis and streptococcal toxic shock
      syndrome. Dextromethorphan (DM), a dextrorotatory morphinan and a widely used
      antitussive drug, has recently been reported to possess anti-inflammatory
      properties. In this study, we investigated the potential protective effect of DM
      in GAS infection using an air pouch infection mouse model. Our results showed
      that DM treatment increased the survival rate of GAS-infected mice. Bacterial
      numbers in the air pouch were lower in mice treated with DM than in those
      infected with GAS alone. The bacterial elimination efficacy was associated with
      increased cell viability and bactericidal activity of air-pouch-infiltrating
      cells. Moreover, DM treatment prevented bacterial dissemination in the blood and
      reduced serum levels of the proinflammatory cytokines interleukin-6 (IL-6), tumor
      necrosis factor alpha (TNF-alpha), and IL-1beta and the chemokines monocyte
      chemotactic protein 1 (MCP-1), macrophage inflammatory protein 2 (MIP-2), and
      RANTES. In addition, GAS-induced mouse liver injury was reduced by DM treatment.
      Taken together, DM can increase bacterial killing and reduce inflammatory
      responses to prevent sepsis in GAS infection. The consideration of DM as an
      adjunct treatment in combination with antibiotics against bacterial infection
      warrants further study.

PMID- 21199931
TI  - Susceptibility of clinical Mycobacterium tuberculosis isolates to a potentially
      less toxic derivate of linezolid, PNU-100480.
AB  - Susceptibility of clinical Mycobacterium tuberculosis isolates to PNU-100480 and
      linezolid was evaluated by the MGIT 960 system. The isolates had various
      susceptibilities to isoniazid (INH), rifampin, ethambutol, and streptomycin. The
      mean MIC for PNU-100480 was 3.2 times lower than that for linezolid. Therefore,
      PNU-100480 is a promising candidate to be developed further as an adjunct in the
      treatment of multidrug- and extensively drug-resistant tuberculosis (MDR/XDR-TB).

PMID- 21199932
TI  - Heat shock proteins and high mobility group box 1 protein lack cytokine function.
AB  - In search of the etiology and pathophysiology for autoimmune and chronic
      inflammatory diseases, many molecules have been identified as endogenous damage
      associated molecules with proinflammatory cytokine functions that may be
      responsible for the sterile inflammation leading to tissue injuries observed in
      these disorders. HSPs and HMGB1 are intracellular molecular chaperones for
      peptides and DNAs, respectively. They are released extracellularly upon cellular
      injury or activation. In vitro studies revealed that HSPs and HMGB1 were capable
      of inducing the release of proinflammatory cytokines by monocytes and macrophages
      and the activation and maturation of DCs. These cytokine effects were reported to
      be mediated by TLR2 and TLR4 signal transduction pathways. Thus, they were called
      endogenous ligands of TLR2 and TLR4 and might serve as danger signals, alarmins,
      or damage-associated molecules to the host immune system. It has been suggested
      that HSPs provide a link between innate and adaptive immune systems, and HMGB1
      functions at the cross-road between innate and adaptive immunity. However, recent
      evidence suggests that highly purified HSPs and HMGB1, although retaining their
      biological activities, do not have cytokine effects. Thus, HSPs and HMGB1 do not
      meet the definition of endogenous ligands of TLRs, danger signals, alarmins, or
      damage-associated molecules. In contrast, HSPs and HMGB1 are found to bind a
      number of pathogen-associated molecules, such as LPS and bacterial lipopeptides,
      and enhance the cytokine effects of these molecules. The significance of these
      cytokine-enhancing effects of HSPs and HMGB1 needs further investigation.

PMID- 21199933
TI  - Molecular engineering of RANTES peptide mimetics with potent anti-HIV-1 activity.
AB  - The chemokine receptor CCR5 is utilized as a critical coreceptor by most primary
      HIV-1 strains. While the lack of structural information on CCR5 has hampered the
      rational design of specific inhibitors, mimetics of the chemokines that naturally
      bind CCR5 can be molecularly engineered. We used a structure-guided approach to
      design peptide mimetics of the N-loop and beta1-strand regions of regulated on
      activation normal T-cell-expressed and secreted (RANTES)/CCL5, which contain the
      primary molecular determinants of HIV-1 blockade. Rational modifications were
      sequentially introduced into the N-loop/beta1-strand sequence, leading to the
      generation of mimetics with potent activity against a broad spectrum of CCR5
      specific HIV-1 isolates (IC(50) range: 104-640 nM) but lacking activity against
      CXCR4-specific HIV-1 isolates. Functional enhancement was initially achieved with
      the stabilization of the N loop in the beta-extended conformation adopted in full
      length RANTES, as confirmed by nuclear magnetic resonance (NMR) analysis.
      However, the most dramatic increase in antiviral potency resulted from the
      engraftment of an in silico-optimized linker segment designed using de novo
      structure-prediction algorithms to stabilize the C-terminal alpha-helix and
      experimentally validated by NMR. Our mimetics exerted CCR5-antagonistic effects,
      demonstrating that the antiviral and proinflammatory functions of RANTES can be
      uncoupled. RANTES peptide mimetics provide new leads for the development of safe
      and effective HIV-1 entry inhibitors.

PMID- 21199934
TI  - Visual influence on path integration in darkness indicates a multimodal
      representation of large-scale space.
AB  - Our ability to return to the start of a route recently performed in darkness is
      thought to reflect path integration of motion-related information. Here we
      provide evidence that motion-related interoceptive representations
      (proprioceptive, vestibular, and motor efference copy) combine with visual
      representations to form a single multimodal representation guiding navigation. We
      used immersive virtual reality to decouple visual input from motion-related
      interoception by manipulating the rotation or translation gain of the visual
      projection. First, participants walked an outbound path with both visual and
      interoceptive input, and returned to the start in darkness, demonstrating the
      influences of both visual and interoceptive information in a virtual reality
      environment. Next, participants adapted to visual rotation gains in the virtual
      environment, and then performed the path integration task entirely in darkness.
      Our findings were accurately predicted by a quantitative model in which visual
      and interoceptive inputs combine into a single multimodal representation guiding
      navigation, and are incompatible with a model of separate visual and
      interoceptive influences on action (in which path integration in darkness must
      rely solely on interoceptive representations). Overall, our findings suggest that
      a combined multimodal representation guides large-scale navigation, consistent
      with a role for visual imagery or a cognitive map.

PMID- 21199935
TI  - Rapid neocortical acquisition of long-term arbitrary associations independent of
      the hippocampus.
AB  - Anterograde amnesia following hippocampal damage involves the loss of the
      capacity to form new declarative memories but leaves nondeclarative memory
      processes intact. Current theories of declarative memory suggest the existence of
      two complementary memory systems: a hippocampal-based system that specializes in
      rapid acquisition of specific events and a neocortical system that slowly learns
      through environmental statistical regularities and requires the initial support
      of the hippocampal system. Contrary to this notion, we demonstrate a
      neurocognitive mechanism that enables rapid acquisition of novel arbitrary
      associations independently of the hippocampus. This mechanism has been dubbed
      "fast mapping" (FM) and is believed to support the rapid acquisition of
      vocabulary in children as young as 16 mo of age. We used FM to teach novel word
      picture associations to four profoundly amnesic patients with hippocampal system
      damage. Patients were able to acquire arbitrary associations through FM normally,
      despite profound impairment on a matched standard associative memory task. Most
      importantly, they retained what they learned through FM after a week's delay,
      when they were around chance level on the standard task. By contrast, two
      patients with unilateral damage to the left polar temporal neocortex were
      impaired on FM, suggesting that this cortical region is critical for associative
      learning through FM. Left perirhinal and entorhinal cortices might also play a
      role in learning through FM. Contrary to current theories, these findings
      indicate that rapid acquisition of declarative-like (relational) memory can be
      accomplished independently of the hippocampus and that neocortical plasticity can
      be induced rapidly to support novel arbitrary associations.

PMID- 21199936
TI  - Selenoprotein TRXR-1 and GSR-1 are essential for removal of old cuticle during
      molting in Caenorhabditis elegans.
AB  - Selenoproteins, in particular thioredoxin reductase, have been implicated in
      countering oxidative damage occurring during aging but the molecular functions of
      these proteins have not been extensively investigated in different animal models.
      Here we demonstrate that TRXR-1 thioredoxin reductase, the sole selenoprotein in
      Caenorhabditis elegans, does not protect against acute oxidative stress but
      functions instead together with GSR-1 glutathione reductase to promote the
      removal of old cuticle during molting. We show that the oxidation state of
      disulfide groups in the cuticle is tightly regulated during the molting cycle,
      and that when trxr-1 and gsr-1 function is reduced, disulfide groups in the
      cuticle remain oxidized. A selenocysteine-to-cysteine TRXR-1 mutant fails to
      rescue molting defects. Furthermore, worms lacking SELB-1, the C. elegans homolog
      of Escherichia coli SelB or mammalian EFsec, a translation elongation factor
      known to be specific for selenocysteine in E. coli, fail to incorporate
      selenocysteine, and display the same phenotype as those lacking trxr-1. Thus,
      TRXR-1 function in the reduction of old cuticle is strictly selenocysteine
      dependent in the nematode. Exogenously supplied reduced glutathione reduces
      disulfide groups in the cuticle and induces apolysis, the separation of old and
      new cuticle, strongly suggesting that molting involves the regulated reduction of
      cuticle components driven by TRXR-1 and GSR-1. Using dauer larvae, we demonstrate
      that aged worms have a decreased capacity to molt, and decreased expression of
      GSR-1. Together, our results establish a function for the selenoprotein TRXR-1
      and GSR-1 in the removal of old cuticle from the surface of epidermal cells.

PMID- 21199937
TI  - Mapping a sensory-motor network onto a structural and functional ground plan in
      the hindbrain.
AB  - The hindbrain of larval zebrafish contains a relatively simple ground plan in
      which the neurons throughout it are arranged into stripes that represent broad
      neuronal classes that differ in transmitter identity, morphology, and
      transcription factor expression. Within the stripes, neurons are stacked
      continuously according to age as well as structural and functional properties,
      such as axonal extent, input resistance, and the speed at which they are
      recruited during movements. Here we address the question of how particular
      networks among the many different sensory-motor networks in hindbrain arise from
      such an orderly plan. We use a combination of transgenic lines and pairwise patch
      recording to identify excitatory and inhibitory interneurons in the hindbrain
      network for escape behaviors initiated by the Mauthner cell. We map this network
      onto the ground plan to show that an individual hindbrain network is built by
      drawing components in predictable ways from the underlying broad patterning of
      cell types stacked within stripes according to their age and structural and
      functional properties. Many different specialized hindbrain networks may arise
      similarly from a simple early patterning.

PMID- 21199938
TI  - Myelination transition zone astrocytes are constitutively phagocytic and have
      synuclein dependent reactivity in glaucoma.
AB  - Optic nerve head (ONH) astrocytes have been proposed to play both protective and
      deleterious roles in glaucoma. We now show that, within the postlaminar ONH
      myelination transition zone (MTZ), there are astrocytes that normally express Mac
      2 (also known as Lgals3 or galectin-3), a gene typically expressed only in
      phagocytic cells. Surprisingly, even in healthy mice, MTZ and other ONH
      astrocytes constitutive internalize large axonal evulsions that contain whole
      organelles. In mouse glaucoma models, MTZ astrocytes further up-regulate Mac-2
      expression. During glaucomatous degeneration, there are dystrophic processes in
      the retina and optic nerve, including the MTZ, which contain protease resistant
      gamma-synuclein. The increased Mac-2 expression by MTZ astrocytes during glaucoma
      likely depends on this gamma-synuclein, as mice lacking gamma-synuclein fail to
      up-regulate Mac-2 at the MTZ after elevation of intraocular pressure. These
      results suggest the possibility that a newly discovered normal degradative
      pathway for axons might contribute to glaucomatous neurodegeneration.

PMID- 21199939
TI  - Simulation of surface processes.
AB  - Computer simulations of surface processes can reveal unexpected insight regarding
      atomic-scale structure and transitions. Here, the strengths and weaknesses of
      some commonly used approaches are reviewed as well as promising avenues for
      improvements. The electronic degrees of freedom are usually described by gradient
      dependent functionals within Kohn-Sham density functional theory. Although this
      level of theory has been remarkably successful in numerous studies, several
      important problems require a more accurate theoretical description. It is
      important to develop new tools to make it possible to study, for example,
      localized defect states and band gaps in large and complex systems. Preliminary
      results presented here show that orbital density-dependent functionals provide a
      promising avenue, but they require the development of new numerical methods and
      substantial changes to codes designed for Kohn-Sham density functional theory.
      The nuclear degrees of freedom can, in most cases, be described by the classical
      equations of motion; however, they still pose a significant challenge, because
      the time scale of interesting transitions, which typically involve substantial
      free energy barriers, is much longer than the time scale of vibrations--often 10
      orders of magnitude. Therefore, simulation of diffusion, structural annealing,
      and chemical reactions cannot be achieved with direct simulation of the classical
      dynamics. Alternative approaches are needed. One such approach is transition
      state theory as implemented in the adaptive kinetic Monte Carlo algorithm, which,
      thus far, has relied on the harmonic approximation but could be extended and made
      applicable to systems with rougher energy landscape and transitions through
      quantum mechanical tunneling.

PMID- 21199940
TI  - Meiotic, cryptic, and stable unannotated transcripts: noncoding RNAs add to the
      epigenetic tool box controlling meiotic development.

PMID- 21199941
TI  - Causes of lifetime fitness of Darwin's finches in a fluctuating environment.
AB  - The genetic basis of variation in fitness of many organisms has been studied in
      the laboratory, but relatively little is known of fitness variation in natural
      environments or its causes. Lifetime fitness (recruitment) may be determined
      solely by producing many offspring, modified by stochastic effects on their
      subsequent survival up to the point of breeding, or by an additional contribution
      made by the high quality of the offspring owing to nonrandom mate choice. To
      investigate the determinants of lifetime fitness, we measured offspring
      production, longevity, and lifetime number of mates in four cohorts of two long
      lived species of socially monogamous Darwin's finch species, Geospiza fortis and
      G. scandens, on the equatorial Galapagos Island of Daphne Major. Regression
      analysis showed that the lifetime production of fledglings was predicted by
      lifetime number of clutches and that recruitment was predicted by lifetime number
      of fledglings and longevity. There was little support for a hypothesis of
      selective mating by females. The offspring sired by extrapair mates were no more
      fit in terms of recruitment than were half-sibs sired by social mates. These
      findings provide insight into the evolution of life history strategies of
      tropical birds. Darwin's finches deviate from the standard tropical pattern of a
      slow pace of life by combining tropical (long lifespan) and temperate (large
      clutch size) characteristics. Our study of fitness shows why this is so in terms
      of selective pressures (fledgling production and adult longevity) and ecological
      opportunities (pulsed food supply and relatively low predation).

PMID- 21199942
TI  - A shift toward birthing relatively large infants early in human evolution.
AB  - It has long been argued that modern human mothers give birth to proportionately
      larger babies than apes do. Data presented here from human and chimpanzee
      infant:mother dyads confirm this assertion: humans give birth to infants
      approximately 6% of their body mass, compared with approximately 3% for
      chimpanzees, even though the female body weights of the two species are
      moderately convergent. Carrying a relatively large infant both pre- and
      postnatally has important ramifications for birthing strategies, social systems,
      energetics, and locomotion. However, it is not clear when the shift to birthing
      large infants occurred over the course of human evolution. Here, known and often
      conserved relationships between adult brain mass, neonatal brain mass, and
      neonatal body mass in anthropoids are used to estimate birthweights of extinct
      hominid taxa. These estimates are resampled with direct measurements of fossil
      postcrania from female hominids, and also compared with estimates of female body
      mass to assess when human-like infant:mother mass ratios (IMMRs) evolved. The
      results of this study suggest that 4.4-Myr-old Ardipithecus possessed IMMRs
      similar to those found in African apes, indicating that a low IMMR is the
      primitive condition in hominids. Australopithecus females, in contrast, had
      significantly heavier infants compared with dimensions of the femoral head (n =
      7) and ankle (n = 7) than what is found in chimpanzees, and are estimated to have
      birthed neonates more than 5% of their body mass. Carrying such proportionately
      large infants may have limited arboreality in Australopithecus females and may
      have selected for alloparenting behavior earlier in human evolution than
      previously thought.

PMID- 21199943
TI  - Patterns of widespread decline in North American bumble bees.
AB  - Bumble bees (Bombus) are vitally important pollinators of wild plants and
      agricultural crops worldwide. Fragmentary observations, however, have suggested
      population declines in several North American species. Despite rising concern
      over these observations in the United States, highlighted in a recent National
      Academy of Sciences report, a national assessment of the geographic scope and
      possible causal factors of bumble bee decline is lacking. Here, we report results
      of a 3-y interdisciplinary study of changing distributions, population genetic
      structure, and levels of pathogen infection in bumble bee populations across the
      United States. We compare current and historical distributions of eight species,
      compiling a database of >73,000 museum records for comparison with data from
      intensive nationwide surveys of >16,000 specimens. We show that the relative
      abundances of four species have declined by up to 96% and that their surveyed
      geographic ranges have contracted by 23-87%, some within the last 20 y. We also
      show that declining populations have significantly higher infection levels of the
      microsporidian pathogen Nosema bombi and lower genetic diversity compared with co
      occurring populations of the stable (nondeclining) species. Higher pathogen
      prevalence and reduced genetic diversity are, thus, realistic predictors of these
      alarming patterns of decline in North America, although cause and effect remain
      uncertain.

PMID- 21199944
TI  - Long-term effects of a trophic cascade in a large lake ecosystem.
AB  - Introductions or invasions of nonnative organisms can mediate major changes in
      the trophic structure of aquatic ecosystems. Here we document multitrophic level
      impacts in a spatially extensive system that played out over more than a century.
      Positive interactions among exotic vertebrate and invertebrate predators caused a
      substantial and abrupt shift in community composition resulting in a trophic
      cascade that extended to primary producers and to a nonaquatic species, the bald
      eagle. The opossum shrimp, Mysis diluviana, invaded Flathead Lake, Montana, the
      largest freshwater lake in the western United States. Lake trout had been
      introduced 80 y prior but remained at low densities until nonnative Mysis became
      established. The bottom-dwelling mysids eliminated a recruitment bottleneck for
      lake trout by providing a deep water source of food where little was available
      previously. Lake trout subsequently flourished on mysids and this voracious
      piscivore now dominates the lake fishery; formerly abundant kokanee were
      extirpated, and native bull and westslope cutthroat trout are imperiled.
      Predation by Mysis shifted zooplankton and phytoplankton community size
      structure. Bayesian change point analysis of primary productivity (27-y time
      series) showed a significant step increase of 55 mg C m(-2) d(-1) (i.e., 21%
      rise) concurrent with the mysid invasion, but little trend before or after
      despite increasing nutrient loading. Mysis facilitated predation by lake trout
      and indirectly caused the collapse of kokanee, redirecting energy flow through
      the ecosystem that would otherwise have been available to other top predators
      (bald eagles).

PMID- 21199945
TI  - Seasonal influenza infection and live vaccine prime for a response to the 2009
      pandemic H1N1 vaccine.
AB  - The robust immune response to a single dose of pandemic 2009 H1N1 vaccine
      suggests that a large segment of the population has been previously primed. We
      evaluated the effect of seasonal (s) H1N1 infection, s-trivalent inactivated
      vaccine (s-TIV), and trivalent s-live attenuated influenza vaccine (s-LAIV)
      before immunization with a pandemic live attenuated influenza vaccine (p-LAIV) in
      mice. We compared serum and mucosal antibody and pulmonary CD8 and CD4 responses
      and the virologic response to challenge with a wild-type 2009 pandemic H1N1 (p
      H1N1) virus. Two doses of p-LAIV induced cellular immune and robust ELISA and
      neutralizing antibody responses that were associated with complete protection
      from p-H1N1 challenge. A single dose of p-LAIV induced a cellular response and
      ELISA but not a neutralizing antibody response, and incomplete protection from p
      H1N1 virus challenge. Primary infection with s-H1N1 influenza virus followed by a
      dose of p-LAIV resulted in cross-reactive ELISA antibodies and a robust cellular
      immune response that was also associated with complete protection from p-H1N1
      virus challenge. A lower-magnitude but similar response associated with partial
      protection was seen in mice that received a dose of s-LAIV followed by p-LAIV.
      Mice that received a dose of s-TIV followed by p-LAIV did not show any evidence
      of priming. In summary, prior infection with a seasonal influenza virus or s-LAIV
      primed mice for a robust response to a single dose of p-LAIV that was associated
      with protection equivalent to two doses of the matched pandemic vaccine.

PMID- 21199946
TI  - Evolution of molecular error rates and the consequences for evolvability.
AB  - Making genes into gene products is subject to predictable errors, each with a
      phenotypic effect that depends on a normally cryptic sequence. Many cryptic
      sequences have strongly deleterious effects, for example when they cause protein
      misfolding. Strongly deleterious effects can be avoided globally by avoiding
      making errors (e.g., via proofreading machinery) or locally by ensuring that each
      error has a relatively benign effect. The local solution requires powerful
      selection acting on every cryptic site and so evolves only in large populations.
      Small populations with less effective selection evolve global solutions. Here we
      show that for a large range of realistic intermediate population sizes, the
      evolutionary dynamics are bistable and either solution may result. The local
      solution facilitates the genetic assimilation of cryptic genetic variation and
      therefore substantially increases evolvability.

PMID- 21199947
TI  - A structural and functional ground plan for neurons in the hindbrain of
      zebrafish.
AB  - The vertebrate hindbrain contains various sensory-motor networks controlling
      movements of the eyes, jaw, head, and body. Here we show that stripes of neurons
      with shared neurotransmitter phenotype that extend throughout the hindbrain of
      young zebrafish reflect a broad underlying structural and functional patterning.
      The neurotransmitter stripes contain cell types with shared gross morphologies
      and transcription factor markers. Neurons within a stripe are stacked
      systematically by extent and location of axonal projections, input resistance,
      and age, and are recruited along the axis of the stripe during behavior. The
      implication of this pattern is that the many networks in hindbrain are
      constructed from a series of neuronal components organized into stripes that are
      ordered from top to bottom according to a neuron's age, structural and functional
      properties, and behavioral roles. This simple organization probably forms a
      foundation for the construction of the networks underlying the many behaviors
      produced by the hindbrain.

PMID- 21199948
TI  - Recovering sound sources from embedded repetition.
AB  - Cocktail parties and other natural auditory environments present organisms with
      mixtures of sounds. Segregating individual sound sources is thought to require
      prior knowledge of source properties, yet these presumably cannot be learned
      unless the sources are segregated first. Here we show that the auditory system
      can bootstrap its way around this problem by identifying sound sources as
      repeating patterns embedded in the acoustic input. Due to the presence of
      competing sounds, source repetition is not explicit in the input to the ear, but
      it produces temporal regularities that listeners detect and use for segregation.
      We used a simple generative model to synthesize novel sounds with naturalistic
      properties. We found that such sounds could be segregated and identified if they
      occurred more than once across different mixtures, even when the same sounds were
      impossible to segregate in single mixtures. Sensitivity to the repetition of
      sound sources can permit their recovery in the absence of other segregation cues
      or prior knowledge of sounds, and could help solve the cocktail party problem.

PMID- 21199949
TI  - rnaset2 mutant zebrafish model familial cystic leukoencephalopathy and reveal a
      role for RNase T2 in degrading ribosomal RNA.
AB  - T2-family acidic endoribonucleases are represented in all genomes. A
      physiological role for RNase T2 has yet to be defined for metazoa. RNASET2
      mutation in humans is linked with a leukoencephalopathy that arises in infancy
      characterized by cortical cysts and multifocal white matter lesions. We now show
      localization of RNASET2 within lysosomes. Further, we demonstrate that loss of
      rnaset2 in mutant zebrafish results in accumulation of undigested rRNA within
      lysosomes within neurons of the brain. Further, by using high field intensity
      magnetic resonance microimaging, we reveal white matter lesions in these animals
      comparable to those observed in RNASET2-deficient infants. This correlates with
      accumulation of Amyloid precursor protein and astrocytes at sites of
      neurodegeneration. Thus we conclude that familial cystic leukoencephalopathy is a
      lysosomal storage disorder in which rRNA is the best candidate for the noxious
      storage material.

PMID- 21199950
TI  - RNS2, a conserved member of the RNase T2 family, is necessary for ribosomal RNA
      decay in plants.
AB  - RNase T2 enzymes are conserved in most eukaryotic genomes, and expression
      patterns and phylogenetic analyses suggest that they may carry out an important
      housekeeping role. However, the nature of this role has been elusive. Here we
      show that RNS2, an intracellular RNase T2 from Arabidopsis thaliana, is essential
      for normal ribosomal RNA recycling. This enzyme is the main endoribonuclease
      activity in plant cells and localizes to the endoplasmic reticulum (ER), ER
      derived structures, and vacuoles. Mutants lacking RNS2 activity accumulate RNA
      intracellularly, and rRNA in these mutants has a longer half-life. Normal rRNA
      turnover seems essential to maintain cell homeostasis because rns2 mutants
      display constitutive autophagy. We propose that RNS2 is part of a process that
      degrades rRNA to recycle its components. This process appears to be conserved in
      all eukaryotes.

PMID- 21199951
TI  - Optimal feeding and swimming gaits of biflagellated organisms.
AB  - Locomotion is widely observed in life at micrometric scales and is exhibited by
      many eukaryotic unicellular organisms. Motility of such organisms can be achieved
      through periodic deformations of a tail-like projection called the eukaryotic
      flagellum. Although the mechanism allowing the flagellum to deform is largely
      understood, questions related to the functional significance of the observed
      beating patterns remain unresolved. Here, we focus our attention on the stroke
      patterns of biflagellated phytoplanktons resembling the green alga Chlamydomonas.
      Such organisms have been widely observed to beat their flagella in two different
      ways--a breaststroke and an undulatory stroke--both of which are prototypical of
      general beating patterns observed in eukaryotes. We develop a general
      optimization procedure to determine the existence of optimal swimming gaits and
      investigate their functional significance with respect to locomotion and nutrient
      uptake. Both the undulatory and the breaststroke represent local optima for
      efficient swimming. With respect to the generation of feeding currents, we found
      the breaststroke to be optimal and to enhance nutrient uptake significantly,
      particularly when the organism is immersed in a gradient of nutrients.

PMID- 21199952
TI  - Nutrient regime shift in the western North Atlantic indicated by compound
      specific delta15N of deep-sea gorgonian corals.
AB  - Despite the importance of the nitrogen (N) cycle on marine productivity, little
      is known about variability in N sources and cycling in the ocean in relation to
      natural and anthropogenic climate change. Beyond the last few decades of
      scientific observation, knowledge depends largely on proxy records derived from
      nitrogen stable isotopes (delta(15)N) preserved in sediments and other
      bioarchives. Traditional bulk delta(15)N measurements, however, represent the
      combined influence of N source and subsequent trophic transfers, often
      confounding environmental interpretation. Recently, compound-specific analysis of
      individual amino acids (delta(15)N-AA) has been shown as a means to deconvolve
      trophic level versus N source effects on the delta(15)N variability of bulk
      organic matter. Here, we demonstrate the first use of delta(15)N-AA in a
      paleoceanographic study, through analysis of annually secreted growth rings
      preserved in the organic endoskeletons of deep-sea gorgonian corals. In the
      Northwest Atlantic off Nova Scotia, coral delta(15)N is correlated with
      increasing presence of subtropical versus subpolar slope waters over the
      twentieth century. By using the new delta(15)N-AA approach to control for
      variable trophic processing, we are able to interpret coral bulk delta(15)N
      values as a proxy for nitrate source and, hence, slope water source partitioning.
      We conclude that the persistence of the warm, nutrient-rich regime since the
      early 1970s is largely unique in the context of the last approximately 1,800 yr.
      This evidence suggests that nutrient variability in this region is coordinated
      with recent changes in global climate and underscores the broad potential of
      delta(15)N-AA for paleoceanographic studies of the marine N cycle.

PMID- 21199953
TI  - Continuous-time model of structural balance.
AB  - It is not uncommon for certain social networks to divide into two opposing camps
      in response to stress. This happens, for example, in networks of political
      parties during winner-takes-all elections, in networks of companies competing to
      establish technical standards, and in networks of nations faced with mounting
      threats of war. A simple model for these two-sided separations is the dynamical
      system dX/dt = X(2), where X is a matrix of the friendliness or unfriendliness
      between pairs of nodes in the network. Previous simulations suggested that only
      two types of behavior were possible for this system: Either all relationships
      become friendly or two hostile factions emerge. Here we prove that for generic
      initial conditions, these are indeed the only possible outcomes. Our analysis
      yields a closed-form expression for faction membership as a function of the
      initial conditions and implies that the initial amount of friendliness in large
      social networks (started from random initial conditions) determines whether they
      will end up in intractable conflict or global harmony.

PMID- 21199954
TI  - Stable structural color patterns displayed on transparent insect wings.
AB  - Color patterns play central roles in the behavior of insects, and are important
      traits for taxonomic studies. Here we report striking and stable structural color
      patterns--wing interference patterns (WIPs)--in the transparent wings of small
      Hymenoptera and Diptera, patterns that have been largely overlooked by
      biologists. These extremely thin wings reflect vivid color patterns caused by
      thin film interference. The visibility of these patterns is affected by the way
      the insects display their wings against various backgrounds with different light
      properties. The specific color sequence displayed lacks pure red and matches the
      color vision of most insects, strongly suggesting that the biological
      significance of WIPs lies in visual signaling. Taxon-specific color patterns are
      formed by uneven membrane thickness, pigmentation, venation, and hair placement.
      The optically refracted pattern is also stabilized by microstructures of the wing
      such as membrane corrugations and spherical cell structures that reinforce the
      pattern and make it essentially noniridescent over a large range of light
      incidences. WIPs can be applied to map the micromorphology of wings through
      direct observation and are useful in several fields of biology. We demonstrate
      their usefulness as identification patterns to solve cases of cryptic species
      complexes in tiny parasitic wasps, and indicate their potentials for research on
      the genetic control of wing development through direct links between the
      transregulatory wing landscape and interference patterns we observe in Drosophila
      model species. Some species display sexually dimorphic WIPs, suggesting sexual
      selection as one of the driving forces for their evolution.

PMID- 21199955
TI  - Strain-specific activation of the NF-kappaB pathway by GRA15, a novel Toxoplasma
      gondii dense granule protein.
AB  - NF-kappaB is an integral component of the immune response to Toxoplasma gondii.
      Although evidence exists that T. gondii can directly modulate the NF-kappaB
      pathway, the parasite-derived effectors involved are unknown. We determined that
      type II strains of T. gondii activate more NF-kappaB than type I or type III
      strains, and using forward genetics we found that this difference is a result of
      the polymorphic protein GRA15, a novel dense granule protein which T. gondii
      secretes into the host cell upon invasion. A GRA15-deficient type II strain has a
      severe defect in both NF-kappaB nuclear translocation and NF-kappaB-mediated
      transcription. Furthermore, human cells expressing type II GRA15 also activate NF
      kappaB, demonstrating that GRA15 alone is sufficient for NF-kappaB activation.
      Along with the rhoptry protein ROP16, GRA15 is responsible for a large part of
      the strain differences in the induction of IL-12 secretion by infected mouse
      macrophages. In vivo bioluminescent imaging showed that a GRA15-deficient type II
      strain grows faster compared with wild-type, most likely through its reduced
      induction of IFN-gamma. These results show for the first time that a dense
      granule protein can modulate host signaling pathways, and dense granule proteins
      can therefore join rhoptry proteins in T. gondii's host cell-modifying arsenal.

PMID- 21199956
TI  - A highly tilted binding mode by a self-reactive T cell receptor results in
      altered engagement of peptide and MHC.
AB  - Self-reactive T cells that escape elimination in the thymus can cause autoimmune
      pathology, and it is therefore important to understand the structural mechanisms
      of self-antigen recognition. We report the crystal structure of a T cell receptor
      (TCR) from a patient with relapsing-remitting multiple sclerosis that engages its
      self-peptide-major histocompatibility complex (pMHC) ligand in an unusual manner.
      The TCR is bound in a highly tilted orientation that prevents interaction of the
      TCR-alpha chain with the MHC class II beta chain helix. In this structure, only a
      single germline-encoded TCR loop engages the MHC protein, whereas in most other
      TCR-pMHC structures all four germline-encoded TCR loops bind to the MHC helices.
      The tilted binding mode also prevents peptide contacts by the short
      complementarity-determining region (CDR) 3beta loop, and interactions that
      contribute to peptide side chain specificity are focused on the CDR3alpha loop.
      This structure is the first example in which only a single germline-encoded TCR
      loop contacts the MHC helices. Furthermore, the reduced interaction surface with
      the peptide may facilitate TCR cross-reactivity. The structural alterations in
      the trimolecular complex are distinct from previously characterized self-reactive
      TCRs, indicating that there are multiple unusual ways for self-reactive TCRs to
      bind their pMHC ligand.

PMID- 21199957
TI  - Effect of bupropion treatment on brain activation induced by cigarette-related
      cues in smokers.
AB  - CONTEXT: Nicotine-dependent smokers exhibit craving and brain activation in the
      prefrontal and limbic regions when presented with cigarette-related cues.
      Bupropion hydrochloride treatment reduces cue-induced craving in cigarette
      smokers; however, the mechanism by which bupropion exerts this effect has not yet
      been described. OBJECTIVE: To assess changes in regional brain activation in
      response to cigarette-related cues from before to after treatment with bupropion
      (vs placebo). DESIGN: Randomized, double-blind, before-after controlled trial.
      SETTING: Academic brain imaging center. PARTICIPANTS: Thirty nicotine-dependent
      smokers (paid volunteers). INTERVENTIONS: Participants were randomly assigned to
      receive 8 weeks of treatment with either bupropion or a matching placebo pill
      (double-blind). MAIN OUTCOME MEASURES: Subjective cigarette craving ratings and
      regional brain activations (blood oxygen level-dependent response) in response to
      viewing cue videos. RESULTS: Bupropion-treated participants reported less craving
      and exhibited reduced activation in the left ventral striatum, right medial
      orbitofrontal cortex, and bilateral anterior cingulate cortex from before to
      after treatment when actively resisting craving compared with placebo-treated
      participants. When resisting craving, reduction in self-reported craving
      correlated with reduced regional brain activation in the bilateral medial
      orbitofrontal and left anterior cingulate cortices in all participants.
      CONCLUSIONS: Treatment with bupropion is associated with improved ability to
      resist cue-induced craving and a reduction in cue-induced activation of limbic
      and prefrontal brain regions, while a reduction in craving, regardless of
      treatment type, is associated with reduced activation in prefrontal brain
      regions.

PMID- 21199958
TI  - Effects of varenicline on smoking cue-triggered neural and craving responses.
AB  - CONTEXT: Varenicline, an effective smoking cessation medication, functions as an
      alpha4beta2 nicotinic acetylcholine receptor partial agonist. It indirectly
      affects the dopaminergic reward system by reducing withdrawal symptoms during
      abstinence and by decreasing the reinforcement received from nicotine while
      smoking. We hypothesize that varenicline would have a third mechanism to blunt
      responses to smoking cues in the reward-related ventral striatum and medial
      orbitofrontal cortex and would be associated with a reduction in smoking cue
      elicited craving. DESIGN: A laboratory model of conditioned responding and
      arterial spin-labeled perfusion functional magnetic resonance imaging, a
      biomarker of regional brain activity, was used to test our hypothesis. Perfusion
      functional magnetic resonance imaging is quantitative and stable across time,
      facilitating the measurement of medication-induced neural modifications in the
      brain in response to a challenge (smoking cue exposure) and in the brain in the
      resting condition (without provocation). Smokers were imaged during rest and
      during smoking cue exposure before and after a 3-week randomized placebo
      controlled medication regimen. Subjects were nonabstinent to explicitly examine
      the effects of varenicline on cue reactivity independent of withdrawal. SETTING:
      Center for the Study of Addictions, University of Pennsylvania, Philadelphia.
      Subjects Subjects were nicotine-dependent smokers who responded to advertisements
      placed on local radio and Listservs to participate in a medication-related
      research study that specifically stated "this is not a Quit Smoking Study" and
      "smokers may be contemplating but not currently considering quitting." RESULTS:
      Prerandomization smoking cues vs nonsmoking cues activated the ventral striatum
      and medial orbitofrontal cortex (t = 3.77) and elicited subjective reports of
      craving (P = .006). Craving reports correlated with increased activity in the
      posterior cingulate (t = 4.11). Administration of varenicline diminished smoking
      cue-elicited ventral striatum and medial orbitofrontal cortex responses (t values
      from -3.75 to -5.63) and reduced self-reported smoking cue-elicited craving,
      whereas placebo-treated subjects exhibited responses similar to those observed
      prior to randomization. Varenicline-induced activation of lateral orbitofrontal
      cortex in the brain at rest (t = 5.63) predicted blunting of smoking cue
      responses in the medial orbitofrontal cortex (r = -0.74). CONCLUSIONS:
      Varenicline's reciprocal actions in the reward-activated medial orbitofrontal
      cortex and in the reward-evaluating lateral orbitofrontal cortex underlie a
      diminished smoking cue response, revealing a distinctive new action that likely
      contributes to its clinical efficacy.

PMID- 21199960
TI  - The triumph of Bacchus.

PMID- 21199959
TI  - The serotonin transporter promoter variant (5-HTTLPR), stress, and depression
      meta-analysis revisited: evidence of genetic moderation.
AB  - CONTEXT: Two recent meta-analyses assessed the set of studies exploring the
      interaction between a serotonin transporter promoter polymorphism (5-HTTLPR) and
      stress in the development of depression and concluded that the evidence did not
      support the presence of the interaction. However, even the larger of the meta
      analyses included only 14 of the 56 studies that have assessed the relationship
      between 5-HTTLPR, stress, and depression. OBJECTIVE: To perform a meta-analysis
      including all relevant studies exploring the interaction. DATA SOURCES: We
      identified studies published through November 2009 in PubMed. STUDY SELECTION: We
      excluded 2 studies presenting data that were included in other larger studies.
      DATA EXTRACTION: To perform a more inclusive meta-analysis, we used the Liptak
      Stouffer z score method to combine findings of primary studies at the level of
      significance tests rather than the level of raw data. DATA SYNTHESIS: We included
      54 studies and found strong evidence that 5-HTTLPR moderates the relationship
      between stress and depression, with the 5-HTTLPR s allele associated with an
      increased risk of developing depression under stress (P = .00002). When
      stratifying our analysis by the type of stressor studied, we found strong
      evidence for an association between the s allele and increased stress sensitivity
      in the childhood maltreatment (P = .00007) and the specific medical condition (P
      = .0004) groups of studies but only marginal evidence for an association in the
      stressful life events group (P = .03). When restricting our analysis to the
      studies included in the previous meta-analyses, we found no evidence of
      association (Munafo et al studies, P = .16; Risch et al studies, P = .11). This
      suggests that the difference in results between meta-analyses was due to the
      different set of included studies rather than the meta-analytic technique.
      CONCLUSION: Contrary to the results of the smaller earlier meta-analyses, we find
      strong evidence that the studies published to date support the hypothesis that 5
      HTTLPR moderates the relationship between stress and depression.

PMID- 21199961
TI  - A dimensional-spectrum model of psychopathology: progress and opportunities.

PMID- 21199963
TI  - Problem-solving therapy and supportive therapy in older adults with major
      depression and executive dysfunction: effect on disability.
AB  - CONTEXT: Older patients with depression and executive dysfunction represent a
      population with significant disability and a high likelihood of failing
      pharmacotherapy. OBJECTIVES: To examine whether problem-solving therapy (PST)
      reduces disability more than does supportive therapy (ST) in older patients with
      depression and executive dysfunction and whether this effect is mediated by
      improvement in depressive symptoms. DESIGN: Randomized controlled trial. SETTING:
      Weill Cornell Medical College and University of California at San Francisco.
      PARTICIPANTS: Adults (aged >59 years) with major depression and executive
      dysfunction recruited between December 2002 and November 2007 and followed up for
      36 weeks. Intervention Twelve sessions of PST modified for older depressed adults
      with executive impairment or ST. Main Outcome Measure Disability as quantified
      using the 12-item World Health Organization Disability Assessment Schedule II.
      RESULTS: Of 653 individuals referred to this study, 221 met the inclusion
      criteria and were randomized to receive PST or ST. Both PST and ST led to
      comparable improvement in disability in the first 6 weeks of treatment, but a
      more prominent reduction was noted in PST participants at weeks 9 and 12. The
      difference between PST and ST was greater in patients with greater cognitive
      impairment and more previous episodes. Reduction in disability paralleled
      reduction in depressive symptoms. The therapeutic advantage of PST over ST in
      reducing depression was, in part, due to greater reduction in disability by PST.
      Although disability increased during the 24 weeks after the end of treatment, the
      advantage of PST over ST was retained. CONCLUSIONS: These results suggest that
      PST is more effective than ST in reducing disability in older patients with major
      depression and executive dysfunction, and its benefits were retained after the
      end of treatment. The clinical value of this finding is that PST may be a
      treatment alternative in an older patient population likely to be resistant to
      pharmacotherapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00052091.

PMID- 21199962
TI  - The missing p in psychiatric training: why it is important to teach pain to
      psychiatrists.
AB  - CONTEXT: Pain problems are exceedingly prevalent among psychiatric patients.
      Moreover, clinical impressions and neurobiological research suggest that physical
      and psychological aspects of pain are closely related entities. Nonetheless,
      remarkably few pain-related themes are currently included in psychiatric
      residency training. OBJECTIVES: To provide clinical and scientific rationale for
      psychiatric-training enrichment with basic tenets of pain medicine and to raise
      the awareness and sensitivity of physicians, scientists, and educators to this
      important yet unmet clinical and public health need. RESULTS: We present 3 lines
      of translational research evidence, extracted from a comprehensive literature
      review, in support of our objectives. First, the neuroanatomical and functional
      overlap between pain and emotion/reward/motivation brain circuitry suggests
      integration and mutual modulation of these systems. Second, psychiatric disorders
      are commonly associated with alterations in pain processing, whereas chronic pain
      may impair emotional and neurocognitive functioning. Third, given its stressful
      nature, pain may serve as a functional probe for unraveling pathophysiological
      mechanisms inherent in psychiatric morbidity. CONCLUSIONS: Pain training in
      psychiatry will contribute to deeper and more sophisticated insight into both
      pain syndromes and general psychiatric morbidity regardless of patients' pain
      status. Furthermore, it will ease the artificial boundaries separating
      psychiatric and medical formulations of brain disorders, thus fostering cross
      fertilizing interactions among specialists in various disciplines entrusted with
      the care of patients experiencing pain.

PMID- 21199964
TI  - Increased mortality risk in women with depression and diabetes mellitus.
AB  - CONTEXT: Depression and diabetes mellitus have been associated with an increased
      risk of all-cause and cardiovascular disease (CVD) mortality. However, data
      evaluating the joint effects of these 2 conditions on mortality are sparse.
      OBJECTIVES: To evaluate the individual and joint effects of depression and
      diabetes on all-cause and CVD mortality rate. DESIGN: Prospective cohort study.
      SETTING: The 11 states of the Nurses' Health Study. PARTICIPANTS: A total of 78
      282 women who participated in the Nurses' Health Study aged 54 to 79 years at
      baseline in 2000 were followed up until 2006. Depression was defined as having
      self-reported diagnosed depression, treatment with antidepressant medications, or
      a score indicating severe depressive symptoms (ie, a 5-item Mental Health Index
      score <=52). Self-reported type 2 diabetes was confirmed using a supplementary
      questionnaire. MAIN OUTCOME MEASURES: All-cause and CVD-specific mortality rate.
      RESULTS: During 6 years of follow-up (433 066 person-years), 4654 deaths were
      documented, including 979 deaths from CVD. Compared with participants without
      either condition, the age-adjusted relative risks (RRs) (95% confidence interval)
      for all-cause mortality were 1.76 (1.64-1.89) for women with depression only,
      1.71 (1.54-1.89) for individuals with diabetes only, and 3.11 (2.70-3.58) for
      women with both conditions. The corresponding age-adjusted RRs of CVD mortality
      were 1.81 (1.54-2.13), 2.67 (2.20-3.23), and 5.38 (4.19-6.91), respectively.
      These associations were attenuated after multivariate adjustment for other
      demographic variables, body mass index, smoking status, alcohol intake, physical
      activity, and major comorbidities (including hypertension, hypercholesterolemia,
      heart diseases, stroke, and cancer) but remained significant, with the highest
      RRs for all-cause and CVD mortality found in those with both conditions (2.07
      [1.79-2.40] and 2.72 [2.09-3.54], respectively). Furthermore, the combination of
      depression with a long duration of diabetes mellitus (ie, >10 years) or insulin
      therapy was associated with a particularly higher risk of CVD mortality after
      multivariate adjustment (RRs, 3.22 and 4.90, respectively). CONCLUSIONS:
      Depression and diabetes are associated with a significantly increased risk of all
      cause and CVD mortality rate. The coexistence of these conditions identifies
      women at particularly high risk.

PMID- 21199965
TI  - Maintenance treatment of depression in old age: a randomized, double-blind,
      placebo-controlled evaluation of the efficacy and safety of donepezil combined
      with antidepressant pharmacotherapy.
AB  - CONTEXT: Cognitive impairment in late-life depression is a core feature of the
      illness. OBJECTIVE: To test whether donepezil hydrochloride and antidepressant
      therapy is superior to placebo and antidepressant therapy in improving cognitive
      performance and instrumental activities of daily living and in reducing
      recurrences of depression over 2 years of maintenance treatment. DESIGN:
      Randomized, double-blind, placebo-controlled maintenance trial. SETTING:
      University clinic. PARTICIPANTS: One hundred thirty older adults aged 65 years
      and older with recently remitted major depression. INTERVENTIONS: Random
      assignment to maintenance antidepressant pharmacotherapy and donepezil or to
      maintenance antidepressant pharmacotherapy and placebo. MAIN OUTCOME MEASURES:
      Global neuropsychological performance, cognitive instrumental activities of daily
      living, and recurrent depression. RESULTS: Donepezil and antidepressant therapy
      temporarily improved global cognition (treatment * time interaction, F2,216 =
      3.78; P = .03), but effect sizes were small (Cohen d = 0.27, group difference at
      1 year). A marginal benefit to cognitive instrumental activities of daily living
      was also observed (treatment * time interaction, F2,137 = 2.94; P = .06). The
      donepezil group was more likely than the placebo group to experience recurrent
      major depression (35% [95% confidence interval {CI}, 24%-46%] vs 19% [95% CI, 9%
      29%], respectively; log-rank chi2 = 3.97; P = .05; hazard ratio = 2.09 [95% CI,
      1.00-4.41]). Post hoc subgroup analyses showed that of 57 participants with mild
      cognitive impairment, 3 of 30 participants (10% [95% CI, 0%-21%]) receiving
      donepezil and 9 of 27 participants (33% [95% CI, 16%-51%]) receiving placebo had
      a conversion to dementia over 2 years (Fisher exact test, P = .05). The mild
      cognitive impairment subgroup had recurrence rates of major depression of 44%
      with donepezil vs 12% with placebo (likelihood ratio = 4.91; P = .03). The
      subgroup with normal cognition (n = 73) showed no benefit with donepezil and no
      increase in recurrence of major depression. CONCLUSIONS: Whether a cholinesterase
      inhibitor should be used as augmentation in the maintenance treatment of late
      life depression depends on a careful weighing of risks and benefits in those with
      mild cognitive impairment. In cognitively intact patients, donepezil appears to
      have no clear benefit for preventing progression to mild cognitive impairment or
      dementia or for preventing recurrence of depression. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00177671.

PMID- 21199966
TI  - Bright light treatment in elderly patients with nonseasonal major depressive
      disorder: a randomized placebo-controlled trial.
AB  - CONTEXT: Major depressive disorder (MDD) in elderly individuals is prevalent and
      debilitating. It is accompanied by circadian rhythm disturbances associated with
      impaired functioning of the suprachiasmatic nucleus, the biological clock of the
      brain. Circadian rhythm disturbances are common in the elderly. Suprachiasmatic
      nucleus stimulation using bright light treatment (BLT) may, therefore, improve
      mood, sleep, and hormonal rhythms in elderly patients with MDD. OBJECTIVE: To
      determine the efficacy of BLT in elderly patients with MDD. DESIGN: Double-blind,
      placebo-controlled randomized clinical trial. SETTING: Home-based treatment in
      patients recruited from outpatient clinics and from case-finding using general
      practitioners' offices in the Amsterdam region. PARTICIPANTS: Eighty-nine
      outpatients 60 years or older who had MDD underwent assessment at baseline (T0),
      after 3 weeks of treatment (T1), and 3 weeks after the end of treatment (T2).
      Intervention Three weeks of 1-hour early-morning BLT (pale blue, approximately
      7500 lux) vs placebo (dim red light, approximately 50 lux). MAIN OUTCOME
      MEASURES: Mean improvement in Hamilton Scale for Depression scores at T1 and T2
      using parameters of sleep and cortisol and melatonin levels. RESULTS: Intention
      to-treat analysis showed Hamilton Scale for Depression scores to improve with BLT
      more than placebo from T0 to T1 (7%; 95% confidence interval, 4%-23%; P = .03)
      and from T0 to T2 (21%; 7%-31%; P = .001). At T1 relative to T0, get-up time
      after final awakening in the BLT group advanced by 7% (P < .001), sleep
      efficiency increased by 2% (P = .01), and the steepness of the rise in evening
      melatonin levels increased by 81% (P = .03) compared with the placebo group. At
      T2 relative to T0, get-up time was still advanced by 3% (P = .001) and the 24
      hour urinary free cortisol level was 37% lower (P = .003) compared with the
      placebo group. The evening salivary cortisol level had decreased by 34% in the
      BLT group compared with an increase of 7% in the placebo group (P = .02).
      CONCLUSIONS: In elderly patients with MDD, BLT improved mood, enhanced sleep
      efficiency, and increased the upslope melatonin level gradient. In addition, BLT
      produced continuing improvement in mood and an attenuation of cortisol
      hyperexcretion after discontinuation of treatment. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier NCT00332670.

PMID- 21199967
TI  - Longitudinal effects of mild traumatic brain injury and posttraumatic stress
      disorder comorbidity on postdeployment outcomes in national guard soldiers
      deployed to Iraq.
AB  - CONTEXT: Troops deployed to Iraq and Afghanistan are at high risk for exposure to
      combat events resulting in mild traumatic brain injury (MTBI) or concussion and
      posttraumatic stress disorder (PTSD). The longer-term impact of combat-related
      concussion/MTBI and comorbid PTSD on troops' health and well-being is unknown.
      OBJECTIVE: To assess longitudinal associations between concussion/MTBI and PTSD
      symptoms reported in theater and longer-term psychosocial outcomes in combat
      deployed National Guard soldiers. DESIGN: Longitudinal cohort study. Participants
      were surveyed in Iraq 1 month before returning home (time 1) and 1 year later
      (time 2). Self-reports of concussion/MTBI and PTSD were assessed at times 1 and
      2. Based on time 1 concussion/MTBI status (defined as an injury during deployment
      with loss of consciousness or altered mental status) and time 2 postdeployment
      probable PTSD status, soldiers were compared on a range of time 2 psychosocial
      outcomes. PARTICIPANTS: Nine hundred fifty-three US National Guard soldiers.
      SETTING: The time 1 sample was assessed during redeployment transition briefings
      held at military installations in the Iraq combat theater. The time 2 sample was
      assessed using mailed surveys sent to the homes of US National Guard service
      members. MAIN OUTCOME MEASURES: Postconcussive, depression, and physical
      symptoms; alcohol use; social functioning; and quality of life assessed at time 2
      using valid clinical instruments. RESULTS: The rate of self-reported
      concussion/MTBI during deployment was 9.2% at time 1 and 22.0% at time 2.
      Soldiers with a history of concussion/MTBI were more likely than those without to
      report postdeployment postconcussive symptoms and poorer psychosocial outcomes.
      However, after adjusting for PTSD symptoms, concussion/MTBI was not associated
      with postdeployment symptoms or outcomes. Time 1 PTSD symptoms more strongly
      predicted postdeployment symptoms and outcomes than did concussion/MTBI history.
      CONCLUSIONS: Although combat-related PTSD was strongly associated with
      postconcussive symptoms and psychosocial outcomes 1 year after soldiers returned
      from Iraq, there was little evidence of a long-term negative impact of
      concussion/MTBI history on these outcomes after accounting for PTSD. These
      findings and the 2-fold increase in reports of deployment-related concussion/MTBI
      history have important implications for screening and treatment.

PMID- 21199969
TI  - Wide variability in physical activity environments and weather-related outdoor
      play policies in child care centers within a single county of Ohio.
AB  - OBJECTIVES: To examine the variability of physical activity environments and
      outdoor play policies in child care centers and to determine whether this
      variability is associated with the demographic characteristics of the child care
      centers surveyed. DESIGN: Early Learning Environments Physical Activity and
      Nutrition Telephone Survey. SETTING: Child care centers in Hamilton County
      (greater Cincinnati area), Ohio, during the period from 2008 to 2009.
      PARTICIPANTS: Directors of all 185 licensed full-time child care centers in
      Hamilton County. OUTCOME MEASURES: Descriptive measures of playground and indoor
      physical activity environments and weather-related outdoor play policies.
      RESULTS: Of 185 eligible child care centers, 162 (88%) responded to our survey.
      Of the 162 centers that responded, 151 (93%) reported an on-site playground, but
      slightly more than half reported that their playgrounds were large, that they
      were at least one-third covered in shade, or that they had a variety of portable
      play equipment. Only half reported having a dedicated indoor gross motor room
      where children could be active during inclement weather. Only 32 centers (20%)
      allowed children to go outside in temperatures below 32 degrees F (0 degrees C),
      and 70 centers (43%) reported allowing children outdoors during light rain. A
      higher percentage of children receiving tuition assistance was associated with
      lower quality physical activity facilities and stricter weather-related
      practices. National accreditation was associated with more physical activity
      promoting practices. CONCLUSION: We found considerable variability in the indoor
      and outdoor physical activity environments offered by child care centers within a
      single county of Ohio. Depending on the outdoor play policy and options for
      indoor physical activity of a child care center, children's opportunities for
      physical activity can be curtailed as a result of subfreezing temperatures or
      light rain. Policy changes and education of parents and teachers may be needed to
      ensure that children have ample opportunity for daily physical activity.

PMID- 21199968
TI  - Development of lifetime comorbidity in the World Health Organization world mental
      health surveys.
AB  - CONTEXT: Although numerous studies have examined the role of latent variables in
      the structure of comorbidity among mental disorders, none has examined their role
      in the development of comorbidity. OBJECTIVE: To study the role of latent
      variables in the development of comorbidity among 18 lifetime DSM-IV disorders in
      the World Health Organization World Mental Health Surveys. DESIGN: Nationally or
      regionally representative community surveys. SETTING: Fourteen countries.
      PARTICIPANTS: A total of 21 229 survey respondents. MAIN OUTCOME MEASURES: First
      onset of 18 lifetime DSM-IV anxiety, mood, behavior, and substance disorders
      assessed retrospectively in the World Health Organization Composite International
      Diagnostic Interview. RESULTS: Separate internalizing (anxiety and mood
      disorders) and externalizing (behavior and substance disorders) factors were
      found in exploratory factor analysis of lifetime disorders. Consistently
      significant positive time-lagged associations were found in survival analyses for
      virtually all temporally primary lifetime disorders predicting subsequent onset
      of other disorders. Within-domain (ie, internalizing or externalizing)
      associations were generally stronger than between-domain associations. Most time
      lagged associations were explained by a model that assumed the existence of
      mediating latent internalizing and externalizing variables. Specific phobia and
      obsessive-compulsive disorder (internalizing) and hyperactivity and oppositional
      defiant disorders (externalizing) were the most important predictors. A small
      number of residual associations remained significant after controlling the latent
      variables. CONCLUSIONS: The good fit of the latent variable model suggests that
      common causal pathways account for most of the comorbidity among the disorders
      considered herein. These common pathways should be the focus of future research
      on the development of comorbidity, although several important pairwise
      associations that cannot be accounted for by latent variables also exist that
      warrant further focused study.

PMID- 21199970
TI  - Long-term outcome of brain structure in premature infants: effects of liberal vs
      restricted red blood cell transfusions.
AB  - OBJECTIVE: To assess the long-term outcome of brain structure in preterm infants,
      at an average age of 12 years, who received a red blood cell transfusion for
      anemia of prematurity. DESIGN: As neonates, this cohort of infants participated
      in a clinical trial in which they received red blood cell transfusions based on a
      high pretransfusion hematocrit threshold (liberal group) or a low hematocrit
      threshold (restricted group). These 2 preterm groups were compared with a group
      of full-term healthy control children. SETTING: Tertiary care hospital.
      PARTICIPANTS: Magnetic resonance imaging scans for 44 of the original 100
      subjects were obtained. INTERVENTION: Liberal vs restricted transfusion. MAIN
      OUTCOME MEASURES: Intracranial volume, total brain tissue, total cerebrospinal
      fluid, cerebral cortex and cerebral white matter volume, subcortical nuclei
      volume, and cerebellum volume. RESULTS: Intracranial volume was substantially
      smaller in the liberal group compared with controls. Intracranial volume in the
      restricted group was not different from controls. Whole-cortex volume was not
      different in either preterm group compared with controls. Cerebral white matter
      was substantially reduced in both preterm groups, more so for the liberal group.
      The subcortical nuclei were substantially decreased in volume, equally so for
      both preterm groups compared with controls. When sex effects were evaluated, the
      girls in the liberal group had the most significant abnormalities. CONCLUSION:
      Red blood cell transfusions affected the long-term outcome of premature infants
      as indicated by reduced brain volumes at 12 years of age for neonates who
      received transfusions using liberal guidelines.

PMID- 21199971
TI  - Clostridium difficile infection in hospitalized children in the United States.
AB  - OBJECTIVES: To evaluate the trend in Clostridium difficile infection (CDI) among
      hospitalized children in the United States and to evaluate the severity of and
      risk factors associated with these cases of CDI. DESIGN: A retrospective cohort
      study using the triennial Healthcare Cost and Utilization Project Kids' Inpatient
      Database for the years 1997, 2000, 2003, and 2006. SETTING: Hospitalized children
      in the United States. PARTICIPANTS: A nationally weighted number of patients (10
      474 454) discharged from the hospital, 21 274 of whom had CDI. MAIN EXPOSURE:
      Discharge diagnosis of CDI. MAIN OUTCOME MEASURES: Trend in cases of CDI; effect
      and severity were measured by length of hospital stay, hospitalization charges,
      colectomy rate, and death rate. RESULTS: There was an increasing trend in cases
      of CDI, from 3565 cases in 1997 to 7779 cases in 2006 (P < .001). Patients with
      CDI had an increased risk of death (adjusted odds ratio [OR], 1.20; 95%
      confidence interval [95% CI], 1.01-1.43), colectomy (adjusted OR, 1.36; 95% CI,
      1.04-1.79), a longer length of hospital stay (adjusted OR, 4.34; 95% CI, 3.97
      4.83), and higher hospitalization charges (adjusted OR, 2.12; 95% CI, 1.98-2.26).
      There was no trend in death, colectomy, length of hospital stay, or
      hospitalization charges during the 4 time periods (ie, 1997, 2000, 2003, and
      2006). The risk of comorbid diagnoses associated with CDI included inflammatory
      bowel disease, with an OR of 11.42 (95% CI, 10.16-12.83), and other comorbid
      diagnoses associated with immunosuppression or antibiotic administration.
      CONCLUSIONS: There is an increasing trend in CDI among hospitalized children, and
      this disease is having a significant effect on these children. In contrast to
      adults, there is no increasing trend in the severity of CDI in children. Children
      with medical conditions (including inflammatory bowel disease and
      immunosuppression) or conditions requiring antibiotic administration are at high
      risk of CDI.

PMID- 21199972
TI  - Use of medical imaging procedures with ionizing radiation in children: a
      population-based study.
AB  - OBJECTIVE: To determine population-based rates of the use of diagnostic imaging
      procedures with ionizing radiation in children, stratified by age and sex.
      DESIGN: Retrospective cohort analysis. SETTING: All settings using imaging
      procedures with ionizing radiation. PATIENTS: Individuals younger than 18 years,
      alive, and continuously enrolled in UnitedHealthcare between January 1, 2005, and
      December 31, 2007, in 5 large US health care markets. MAIN OUTCOME MEASURES:
      Number and type of diagnostic imaging procedures using ionizing radiation in
      children. RESULTS: A total of 355 088 children were identified; 436 711 imaging
      procedures using ionizing radiation were performed in 150 930 patients (42.5%).
      The highest rates of use were in children older than 10 years, with frequent use
      in infants younger than 2 years as well. Plain radiography accounted for 84.7% of
      imaging procedures performed. Computed tomographic scans-associated with
      substantially higher doses of radiation-were commonly used, accounting for 11.9%
      of all procedures during the study period. Overall, 7.9% of children received at
      least 1 computed tomographic scan and 3.5% received 2 or more, with computed
      tomographic scans of the head being the most frequent. CONCLUSIONS: Exposure to
      ionizing radiation from medical diagnostic imaging procedures may occur
      frequently among children. Efforts to optimize and ensure appropriate use of
      these procedures in the pediatric population should be encouraged.

PMID- 21199973
TI  - The Archives of Pediatrics & Adolescent Medicine at 100: another turning point in
      medical publishing.

PMID- 21199974
TI  - School, police, and medical authority involvement with children who have
      experienced victimization.
AB  - OBJECTIVE: To obtain national estimates of the degree to which school, police,
      and medical authorities are involved after children experience violence, abuse,
      and crime victimizations. DESIGN: A cross-sectional, national telephone survey
      involving a target sample of 4549 children and youth conducted from January 1,
      2008, through May 31, 2008. SETTING: Contiguous United States. PARTICIPANTS:
      Children and adolescents aged 10 to 17 years and the parents of children aged 0
      to 9 years. OUTCOME MEASURES: Conventional crime, maltreatment, abuse by peer and
      siblings, sexual abuse, and witnessing and indirect exposure to violence.
      RESULTS: A total of 45.7% of children and adolescents who had experienced
      violence in the past year had at least 1 of their victimization incidents known
      to school, police, or medical authorities. For serious victimizations, such as
      sexual abuse by an adult, kidnapping, and gang assaults, authorities knew about
      70.1% or more of the incidents. Awareness, however, was low for peer and sibling
      victimizations, dating violence, and completed and attempted rape. In general,
      school authorities knew about victimizations more often (42.3%) than police
      (12.7%) or medical authorities (1.8%). However, police were the most likely to
      know about kidnapping, neglect, and sexual abuse by any adult. Medical
      authorities were most likely to know about sexual abuse by any adult, gang
      assault, physical abuse by a caretaker, and assault with a weapon. CONCLUSIONS:
      More incidents of victimization and abuse appear to be known to authorities
      currently than was the case in a comparable 1992 survey, but officials should
      improve at identifying a large quantity of victimizations of children and
      adolescents that appear to go undetected.

PMID- 21199975
TI  - Community treatment of posttraumatic stress disorder for children exposed to
      intimate partner violence: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate community-provided trauma-focused cognitive behavior
      therapy (TF-CBT) compared with usual community treatment for children with
      intimate partner violence (IPV)-related posttraumatic stress disorder (PTSD)
      symptoms. DESIGN: Randomized controlled trial conducted using blinded evaluators.
      SETTING: Recruitment, screening, and treatment were conducted at a community IPV
      center between September 1, 2004, and June 30, 2009. PARTICIPANTS: Of 140
      consecutively referred 7- to 14-year-old children, 124 participated.
      INTERVENTIONS: Children and mothers were randomly assigned to receive 8 sessions
      of TF-CBT or usual care (child-centered therapy). MAIN OUTCOME MEASURES: Total
      child PTSD symptoms assessed using child and parent structured interview (Kiddie
      Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version
      [K-SADS-PL]) and self-report (University of California at Los Angeles PTSD
      Reaction Index [RI]). Secondary child outcomes were scores on the K-SADS-PL (PTSD
      symptom clusters), Screen for Child Anxiety Related Emotional Disorders (SCARED)
      (anxiety), Children's Depression Inventory (depression), Kaufman Brief
      Intelligence Test (cognitive functioning), and Child Behavior Checklist (total
      behavior problems). RESULTS: Intent-to-treat analysis using last observation
      carried forward showed superior outcomes for TF-CBT on the total K-SADS-PL (mean
      difference, 1.63; 95% confidence interval [CI], 0.44-2.82), RI (mean difference,
      5.5; 95% CI, 1.37-9.63), K-SADS-PL hyperarousal (mean difference, 0.71; 95% CI,
      0.22-1.20), K-SADS-PL avoidance (0.55; 0.07-1.03), and SCARED (mean difference,
      5.13; 95% CI, 1.31-8.96). Multiple imputation analyses confirmed most of these
      findings. The TF-CBT completers experienced significantly greater PTSD diagnostic
      remission (chi(2) = 4.67, P = .03) and had significantly fewer serious adverse
      events. CONCLUSIONS: Community TF-CBT effectively improves children's IPV-related
      PTSD and anxiety. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00183326.

PMID- 21199976
TI  - Gender-based disparities in infant and child mortality based on maternal exposure
      to spousal violence: the heavy burden borne by Indian girls.
AB  - OBJECTIVES: To examine associations between intimate partner violence (IPV)
      against Indian women and risk of death among their infants and children, as well
      as related gender-based disparities. DESIGN: Analyses of nationally
      representative data to estimate adjusted hazard ratios (aHRs) and attributable
      risks for infant and child mortality based on child gender and on IPV against
      mothers. SETTING: India. PARTICIPANTS: Women aged 15 to 49 years (n = 59,467)
      across all 29 Indian states participating in the Indian National Family Health
      Survey 3 provided information about 158,439 births and about infant and child
      mortality occurring during the 20 years before the survey. MAIN OUTCOME MEASURES:
      Maternal IPV and infant and child (<5 years) mortality among boy vs girl
      children. RESULTS: Infant mortality was greater among infants whose mothers
      experienced IPV (79.2 of 1000 births) vs those whose mothers did not experience
      IPV (59.1 of 1000 births) (aHR, 1.09; 95% confidence interval [CI], 1.03-1.15);
      this effect was significant only for girls (1.15; 1.07-1.24; for boys, 1.04; 0.97
      1.11). Child mortality was also greater among children whose mothers experienced
      IPV (103.6 of 1000 births) vs those whose mothers did not experience IPV (74.8
      per 1000 births) (aHR, 1.10; 95% CI, 1.05-1.15); again, this effect was
      significant only for girls (1.14; 1.07-1.21; for boys, 1.05; 0.99-1.12). An
      estimated 58,021 infant girl deaths and 89,264 girl child deaths were related to
      spousal violence against wives annually, or approximately 1.2 million female
      infant deaths and 1.8 million girl deaths in India between December 1985 and
      August 2005. CONCLUSION: Intimate partner violence against women should be
      considered an urgent priority within programs and policies aimed at maximizing
      survival of children in India, particularly those attempting to increase the
      survival of girls 5 years and younger.

PMID- 21199977
TI  - Experience of an adolescent living with and dying of cancer.
AB  - OBJECTIVE: To provide a unified description of an adolescent's experience of
      living with and dying of cancer. DESIGN: Qualitative analysis using
      phenomenological methods. SETTING: Izaak Walton Killam Health Centre, Halifax,
      Nova Scotia, Canada. PATIENT: A 15-year-old boy who was diagnosed as having
      osteosarcoma in 2003 and died of his disease 1 year later. INTERVENTION: Analysis
      of his 90-page journal that spanned 3 months just before his death. MAIN OUTCOME
      MEASURES: Identification and clustering of key themes to capture the essence of
      his experience. RESULTS: Five main themes that surfaced during analysis of the
      journal were adolescent development, escape from illness, changing relationships,
      symptoms, and spirituality. CONCLUSION: A single case study can provide valuable
      information in a field such as pediatric palliative care in which the patient's
      perspective may be difficult to access or ascertain.

PMID- 21199978
TI  - Primary care strategies for promoting parent-child interactions and school
      readiness in at-risk families: the Bellevue Project for Early Language, Literacy,
      and Education Success.
AB  - OBJECTIVE: To determine the effects of pediatric primary care interventions on
      parent-child interactions in families with low socioeconomic status. DESIGN: In
      this randomized controlled trial, participants were randomized to 1 of 2
      interventions (Video Interaction Project [VIP] or Building Blocks [BB]) or the
      control group. SETTING: Urban public hospital pediatric primary care clinic.
      PARTICIPANTS: Mother-newborn dyads enrolled post partum from November 1, 2005,
      through October 31, 2008. INTERVENTIONS: In the VIP group, mothers and newborns
      participated in 1-on-1 sessions with a child development specialist who
      facilitated interactions in play and shared reading by reviewing videos made of
      the parent and child on primary care visit days; learning materials and parenting
      pamphlets were also provided. In the BB group, parenting materials, including age
      specific newsletters suggesting interactive activities, learning materials, and
      parent-completed developmental questionnaires, were mailed to the mothers. MAIN
      OUTCOME MEASURES: Parent-child interactions were assessed at 6 months with the
      StimQ-Infant and a 24-hour shared reading recall diary. RESULTS: A total of 410
      families were assessed. The VIP group had a higher increased StimQ score (mean
      difference, 3.6 points; 95% confidence interval, 1.5 to 5.6 points; Cohen d,
      0.51; 0.22 to 0.81) and more reading activities compared to the control group.
      The BB group also had an increased overall StimQ score compared with the control
      group (Cohen d, 0.31; 95% confidence interval, 0.03 to 0.60). The greatest
      effects for the VIP group were found for mothers with a ninth-grade or higher
      reading level (Cohen d, 0.68; 95% confidence interval, 0.33 to 1.03).
      CONCLUSIONS: The VIP and BB groups each led to increased parent-child
      interactions. Pediatric primary care represents a significant opportunity for
      enhancing developmental trajectories in at-risk children. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00212576.

PMID- 21199979
TI  - Randomized controlled trial of primary care pediatric parenting programs: effect
      on reduced media exposure in infants, mediated through enhanced parent-child
      interaction.
AB  - OBJECTIVES: To determine whether pediatric primary care-based programs to enhance
      parenting and early child development reduce media exposure and whether enhanced
      parenting mediates the effects. DESIGN: Randomized controlled trial. SETTING:
      Urban public hospital pediatric primary care clinic. PARTICIPANTS: A total of 410
      mother-newborn dyads enrolled after childbirth. INTERVENTIONS: Patients were
      randomly assigned to 1 of 2 interventions, the Video Interaction Project (VIP)
      and Building Blocks (BB) interventions, or to a control group. The VIP
      intervention comprised 1-on-1 sessions with a child development specialist who
      facilitated interactions in play and shared reading through review of videotapes
      made of the parent and child on primary care visit days; learning materials and
      parenting pamphlets were also provided. The BB intervention mailed parenting
      materials, including age-specific newsletters suggesting activities to facilitate
      interactions, learning materials, and parent-completed developmental
      questionnaires (Ages and Stages questionnaires). OUTCOME MEASURES: Electronic
      media exposure in the home using a 24-hour recall diary. RESULTS: The mean (SD)
      exposure at 6 months was 146.5 (125.0) min/d. Exposure to VIP was associated with
      reduced total duration of media exposure compared with the BB and control groups
      (mean [SD] min/d for VIP, 131.6 [118.7]; BB, 151.2 [116.7]; control, 155.4
      [138.7]; P = .009). Enhanced parent-child interactions were found to partially
      mediate relations between VIP and media exposure for families with a ninth grade
      or higher literacy level (Sobel statistic = 2.49; P = .01). CONCLUSION: Pediatric
      primary care may represent an important venue for addressing the public health
      problem of media exposure in young children at a population level. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00212576.

PMID- 21199980
TI  - Adverse adolescent reproductive health outcomes after pelvic inflammatory
      disease.
AB  - OBJECTIVE: To compare longitudinal adolescent and adult reproductive outcomes
      after pelvic inflammatory disease (PID). DESIGN: Secondary analysis of
      longitudinal data from the Pelvic Inflammatory Disease Evaluation and Clinical
      Health study. SETTING: A large multicenter randomized clinical trial assessing
      PID treatment strategies in the United States. PARTICIPANTS: Eight hundred thirty
      one female patients aged 14 to 38 years with a diagnosis of PID. MAIN EXPOSURE:
      Adverse longitudinal outcomes were compared in adolescents (<=19 years) and
      adults (>19 years). OUTCOME MEASURES: Primary outcome measures included recurrent
      sexually transmitted infection at 30 days, recurrent PID, chronic abdominal pain,
      infertility, pregnancy, and times to recurrent PID and pregnancy. Cox
      proportional hazards modeling was used to examine the effect of young age on
      times to pregnancy and recurrent PID. RESULTS: Adolescents were more likely than
      adults to have positive results of sexually transmitted infection testing at
      baseline and at 30 days. There were no significant group differences in chronic
      abdominal pain, infertility, and recurrent PID at 35 or 84 months, but
      adolescents were more likely to have a pregnancy at both time points. Adjusted
      hazard ratios (95% confidence intervals) also demonstrated that adolescents had
      shorter times to pregnancy (1.48 [1.18-1.87]) and recurrent pelvic inflammatory
      disease (1.54 [1.03-2.30]). CONCLUSION: Adolescents may require a different
      approach to clinical care and follow-up after PID to prevent recurrent sexually
      transmitted infections, recurrent PID, and unwanted pregnancies.

PMID- 21199981
TI  - Developmental trajectories of marijuana use from adolescence to adulthood:
      personal predictors.
AB  - OBJECTIVE: To investigate the relationship between early adolescent personal
      characteristics and the developmental trajectories of marijuana use extending
      from early adolescence to adulthood. DESIGN: This study used a longitudinal
      design. Data were obtained using structured questionnaires administered by
      trained interviewers. SETTING: Interviews were conducted in the participants'
      homes in upstate New York. PARTICIPANTS: Participants were drawn from a randomly
      selected cohort and were studied prospectively since 1975 (T1) at a mean age of 6
      years. The follow-up data used for this study were collected at 6 time points
      when the participants were aged between 14 and 37 years in 1983 (T2), 1985-1986
      (T3), 1992 (T4), 1997 (T5), 2002 (T6), and 2005-2006 (T7). MAIN OUTCOME MEASURES:
      Developmental trajectories of marijuana use. RESULTS: Semiparametric group-based
      modeling and logistic regression analyses were used to analyze the data. The
      following 5 distinct trajectories of marijuana use were identified: nonusers or
      experimenters, occasional users, quitters or decreasers, increasing users, and
      chronic users. Chronic users compared with other groups studied (nonusers or
      experimenters, occasional users, quitters or decreasers, and increasing users)
      reported low self-control, externalizing behavior, and an orientation to
      sensation seeking. CONCLUSIONS: Personal attributes of low self-control,
      externalizing behavior, and an orientation to sensation seeking have long-term
      predictive power for distinct trajectories of marijuana use over time. The
      importance of these findings for prevention and treatment programs is discussed.

PMID- 21199982
TI  - Integrating spatial epidemiology into a decision model for evaluation of facial
      palsy in children.
AB  - OBJECTIVE: To develop a novel diagnostic algorithm for Lyme disease among
      children with facial palsy by integrating public health surveillance data with
      traditional clinical predictors. DESIGN: Retrospective cohort study. SETTING:
      Children's Hospital Boston emergency department, 1995-2007. PATIENTS: Two hundred
      sixty-four children (aged <20 years) with peripheral facial palsy who were
      evaluated for Lyme disease. MAIN OUTCOME MEASURES: Multivariate regression was
      used to identify independent clinical and epidemiologic predictors of Lyme
      disease facial palsy. RESULTS: Lyme diagnosis was positive in 65% of children
      from high-risk counties in Massachusetts during Lyme disease season compared with
      5% of those without both geographic and seasonal risk factors. Among patients
      with both seasonal and geographic risk factors, 80% with 1 clinical risk factor
      (fever or headache) and 100% with 2 clinical factors had Lyme disease. Factors
      independently associated with Lyme disease facial palsy were development from
      June to November (odds ratio, 25.4; 95% confidence interval, 8.3-113.4),
      residence in a county where the most recent 3-year average Lyme disease incidence
      exceeded 4 cases per 100,000 (18.4; 6.5-68.5), fever (3.9; 1.5-11.0), and
      headache (2.7; 1.3-5.8). Clinical experts correctly treated 68 of 94 patients
      (72%) with Lyme disease facial palsy, but a tool incorporating geographic and
      seasonal risk identified all 94 cases. CONCLUSIONS: Most physicians intuitively
      integrate geographic information into Lyme disease management, but we demonstrate
      quantitatively how formal use of geographically based incidence in a clinical
      algorithm improves diagnostic accuracy. These findings demonstrate potential for
      improved outcomes from investments in health information technology that foster
      bidirectional communication between public health and clinical settings.

PMID- 21199983
TI  - Factors affecting the stability of blood lipid and lipoprotein levels from youth
      to adulthood: evidence from the Childhood Determinants of Adult Health Study.
AB  - OBJECTIVE: To examine the effect of lifestyle changes on the stability of blood
      lipid and lipoprotein levels from youth to adulthood. DESIGN: Prospective cohort
      study. SETTING: Australia. PARTICIPANTS: Five hundred thirty-nine young adults
      who underwent measurement at baseline in 1985 when aged 9, 12, or 15 years and
      again at follow-up between 2004 and 2006. MAIN EXPOSURES: Changes in adiposity,
      cardiorespiratory fitness, saturated fat intake, smoking, and socioeconomic
      position. MAIN OUTCOME MEASURES: Child and adult blood lipid levels. RESULTS:
      Using established cut points, we found that substantial proportions of
      individuals with high-risk blood lipid and lipoprotein levels at baseline no
      longer had high-risk levels at follow-up. Of the participants who had high-risk
      levels in youth, those with greater increases in adiposity or who commenced or
      continued smoking were more likely to maintain high-risk blood lipid and
      lipoprotein levels (P < .05). Participants who became high risk at follow-up had
      greater increases in adiposity, were less likely to improve their socioeconomic
      position, and tended to become less fit between surveys compared with those who
      maintained normal-risk levels (P <= .05). These effects tended to remain (P <=
      .10) after adjustment for all predictive lifestyle variables. CONCLUSIONS:
      Unhealthy lifestyle changes that occur between youth and adulthood affect whether
      an individual maintains, loses, or develops high-risk blood lipid and lipoprotein
      levels in adulthood. Interventions that promote weight control in the first
      instance, but also physical activity, not smoking, and improved socioeconomic
      position in the transition from youth to adulthood, are likely to be of benefit
      in preventing adult dyslipidemia.

PMID- 21199985
TI  - Picture of the month. Sigmoid volvulus.

PMID- 21199984
TI  - Interventions to reduce sexual risk for human immunodeficiency virus in
      adolescents: a meta-analysis of trials, 1985-2008.
AB  - OBJECTIVE: To provide an updated review of the efficacy of behavioral
      interventions to reduce sexual risk of human immunodeficiency virus (HIV) among
      adolescents. DESIGN: We searched electronic databases, leading public health
      journals, and the document depository held by the Synthesis of HIV/AIDS Risk
      Reduction Project. Studies that fulfilled the selection criteria and were
      available as of December 31, 2008, were included. SETTING: Studies that
      investigated any behavioral intervention advocating sexual risk reduction for HIV
      prevention, sampled adolescents (age range, 11-19 years), measured a behavioral
      outcome relevant to sexual risk, and provided sufficient information to calculate
      effect sizes. PARTICIPANTS: Data from 98 interventions (51,240 participants) were
      derived from 67 studies, dividing for qualitatively different interventions and
      gender when reports permitted it. MAIN OUTCOME MEASURES: Condom use, sexual
      frequency, condom use skills, interpersonal communication skills, condom
      acquisition, and incident sexually transmitted infections (STIs). RESULTS:
      Relative to controls, interventions succeeded at reducing incident STIs,
      increasing condom use, reducing or delaying penetrative sex, and increasing
      skills to negotiate safer sex and to acquire prophylactic protection. Initial
      risk reduction varied depending on sample and intervention characteristics but
      did not decay over time. CONCLUSIONS: Comprehensive behavioral interventions
      reduce risky sexual behavior and prevent transmission of STIs. Interventions are
      most successful to the extent that they deliver intensive content.

PMID- 21199986
TI  - Connecting the dots in childhood and adolescent trauma.

PMID- 21199987
TI  - Developing interventions for trauma-exposed children: a comment on progress to
      date, and 3 recommendations for further advancing the field.

PMID- 21199988
TI  - Predictably unhelpful: why clinicians do not use prediction rules.

PMID- 21199989
TI  - Infant feeding practice of premastication: an anonymous survey among human
      immunodeficiency virus-infected mothers.

PMID- 21199990
TI  - Advice for patients. Lyme disease in children and adolescents.

PMID- 21199992
TI  - Prognostic value of long-term blood pressure variability: the evidence is
      growing.

PMID- 21199991
TI  - Angiotensin II regulates adrenal vascular tone through zona glomerulosa cell
      derived EETs and DHETs.
AB  - Elevated concentrations of aldosterone are associated with several cardiovascular
      diseases. Angiotensin II (Ang II) increases aldosterone secretion and adrenal
      blood flow. This concurrent increase in steroidogenesis and adrenal blood flow is
      not understood. We investigated the role of zona glomerulosa (ZG) cells in the
      regulation of vascular tone of bovine adrenal cortical arteries by Ang II. ZG
      cells enhanced endothelium-dependent relaxations to Ang II. The ZG cell-dependent
      relaxations to Ang II were unchanged by removing the endothelium-dependent
      response to Ang II. These ZG cell-mediated relaxations were ablated by cytochrome
      P450 inhibition, epoxyeicosatrienoic acid (EET) antagonism, and potassium channel
      blockade. Analysis of ZG cell EET production by liquid chromatography/mass
      spectrometry demonstrated an increase in EETs and dihydroxyeicosatrienoic acids
      with Ang II stimulation. These EETs and dihydroxyeicosatrienoic acids produced
      similar concentration-dependent relaxations of adrenal arteries, which were
      attenuated by EET antagonism. Whole-cell potassium currents of adrenal artery
      smooth muscle cells were increased by Ang II stimulation in the presence of ZG
      cells but decreased in the absence of ZG cells. This increase in potassium
      current was abolished by iberiotoxin. Similarly, 14,15-EET induced concentration
      dependent increases in potassium current, which was abolished by iberiotoxin. ZG
      cell aldosterone release was not directly altered by EETs. These data suggest
      that Ang II stimulates ZG cells to release EETs and dihydroxyeicosatrienoic
      acids, resulting in potassium channel activation and relaxation of adrenal
      arteries. This provides a mechanism by which Ang II concurrently increases
      adrenal blood flow and steroidogenesis.

PMID- 21199993
TI  - Orthostatic hypertension: the last hemodynamic frontier.

PMID- 21199994
TI  - Urinary proteomics for prediction of preeclampsia.
AB  - Preeclampsia is a major determinant of fetal and maternal morbidity and
      mortality. We used a proteomic strategy to identify urinary biomarkers that
      predict preeclampsia before the onset of disease. We prospectively collected
      urine samples from women throughout pregnancy. Samples from gestational weeks 12
      to 16 (n=45), 20 (n=50), and 28 (n=18) from women who subsequently had
      preeclampsia develop were matched to controls (n=86, n=49, and n=17,
      respectively). We performed capillary electrophoresis online coupled to micro
      time-of-flight mass spectrometry. Disease-specific peptide patterns were
      generated using support vector machine-based software. Candidate biomarkers were
      sequenced by liquid chromatography-tandem mass spectrometry. From comparison with
      nonpregnant controls, we defined a panel of 284 pregnancy-specific proteomic
      biomarkers. Subsequently, we developed a model of 50 biomarkers from specimens
      obtained at week 28 that was associated with future preeclampsia (classification
      factor in cases, 1.032 +/- 0.411 vs controls, -1.038 +/- 0.432; P<0.001).
      Classification factor increased markedly from week 12 to 16 to 28 in women who
      subsequently had preeclampsia develop (n=16; from -0.392 +/- 0.383 to 1.070 +/-
      0.383; P<0.001) and decreased slightly in controls (n=16; from -0.647 +/- 0.437
      to -1.024 +/- 0.433; P=0.043). Among the biomarkers are fibrinogen alpha chain,
      collagen alpha chain, and uromodulin fragments. The markers appear to predict
      preeclampsia at gestational week 28 with good confidence but not reliably at
      earlier time points (weeks 12-16 and 20). After prospective validation in other
      cohorts, these markers may contribute to better prediction, monitoring, and
      accurate diagnosis of preeclampsia.

PMID- 21199995
TI  - Mineralocorticoid and epidermal growth factor receptors: partners in vivo.

PMID- 21199996
TI  - Can salt sensitivity of blood pressure be assessed without changing salt diet?

PMID- 21199997
TI  - Detecting sodium-sensitivity in hypertensive patients: information from 24-hour
      ambulatory blood pressure monitoring.
AB  - Sodium sensitivity is an important cardiovascular risk factor for which a
      diagnosis requires a time-consuming protocol, the implementation of which is
      often challenging for patients and physicians. Our aim was to assess the
      reliability of an easier approach based on data from 24-hour ambulatory blood
      pressure monitoring performed in hypertensive subjects during daily-life
      conditions and habitual diet. We enrolled 46 mild to moderate hypertensive
      subjects who underwent 24-hour ambulatory blood pressure monitoring during usual
      sodium intake. Patients were divided into 3 classes of sodium sensitivity risk on
      the basis of ambulatory blood pressure monitoring data: low risk if dippers and a
      24-hour heart rate <= 70 bpm; high risk if nondippers and a 24-hour heart rate of
      > 70 bpm; intermediate risk with the remaining combinations (dippers with heart
      rate > 70 bpm or nondippers with heart rate <= 70 bpm). Then patients underwent a
      traditional sodium sensitivity test for the dichotomous classification as sodium
      sensitive or sodium resistant and for evaluating the sodium sensitivity index.
      Prevalence of sodium-sensitive patients and mean value of sodium sensitivity
      index were calculated in the 3 risk classes. The sodium sensitivity index
      markedly and significantly increased from the low-risk to the high-risk class,
      being equal to 19.9 +/- 14.4, 37.8 +/- 8.3, and 68.3 +/- 17.0 mm Hg/(mol/day) in
      the low-risk, intermediate-risk, and high-risk classes, respectively (M +/- SEM).
      Also, the prevalence of sodium-sensitive patients increased significantly from
      the low-risk class (25%) to the intermediate-risk (40%) and high-risk (70%)
      classes. Thus, performance of 24-hour ambulatory blood pressure monitoring in
      daily-life conditions and habitual diet may give useful information on the sodium
      sensitivity condition of hypertensive subjects in an easier manner than with the
      traditional sodium sensitivity test approach.

PMID- 21199998
TI  - Epidermal growth factor receptor mediates the vascular dysfunction but not the
      remodeling induced by aldosterone/salt.
AB  - Pathophysiological aldosterone (aldo)/mineralocorticoid receptor signaling has a
      major impact on the cardiovascular system, resulting in hypertension and vascular
      remodeling. Mineralocorticoids induce endothelial dysfunction, decreasing
      vasorelaxation in response to acetylcholine and increasing the response to
      vasoconstrictors. Activation of the epidermal growth factor receptor (EGFR) is
      thought to mediate the vascular effects of aldo, but this has yet to be
      demonstrated in vivo. In this study, we analyzed the molecular and functional
      vascular consequences of aldo-salt challenge in the waved 2 mouse, a genetic
      model with a partial loss of EGFR tyrosine kinase activity. Deficient EGFR
      activity is associated with global oxidative stress and endothelial dysfunction.
      A decrease in EGFR activity did not affect the arterial wall remodeling process
      induced by aldo-salt. By contrast, normal EGFR activity was required for the aldo
      induced enhancement of phenylephrine- and angiotensin II-mediated
      vasoconstriction. In conclusion, this in vivo study demonstrates that EGFR plays
      a key role in aldosterone-mediated vascular reactivity.

PMID- 21199999
TI  - Postural changes in blood pressure and incidence of ischemic stroke subtypes: the
      ARIC study.
AB  - The relation of orthostatic blood pressure decrease, or increase, with occurrence
      of ischemic stroke subtypes has not been examined. We investigated the
      association of orthostatic blood pressure change (within 2 minutes after supine
      to standing) obtained at baseline (1987 to 1989) in the Atherosclerosis Risk in
      Communities Study with incidence of ischemic stroke subtypes through 2007. Among
      12 817 black and white individuals without a history of stroke at baseline, 680
      ischemic strokes (153 lacunar, 383 nonlacunar thrombotic, and 144 cardioembolic
      strokes) occurred during a median follow-up of 18.7 years. There was a U-shaped
      association between orthostatic systolic blood pressure change and lacunar stroke
      incidence (quadratic P=0.004). In contrast, orthostatic systolic blood pressure
      decrease of 20 mm Hg or more was associated with increased occurrence of
      nonlacunar thrombotic and cardioembolic strokes independent of sitting systolic
      blood pressure, antihypertensive medication use, diabetes, and other lifestyle,
      physiological, biochemical, and medical conditions at baseline (for nonlacunar
      thrombotic: hazard ratio, 2.02; 95% CI, 1.43 to 2.84; for cardioembolic: hazard
      ratio, 1.85, 95% CI, 1.01 to 3.39). Orthostatic diastolic blood pressure decrease
      was associated with increased risk of nonlacunar thrombotic and cardioembolic
      strokes; the hazard ratios (95% CI) associated with 10 mm Hg lower orthostatic
      diastolic blood pressure (continuous) were 1.26 (1.06 to 1.50) and 1.41 (1.06 to
      1.88), respectively, in fully adjusted models. In conclusion, the present study
      found that nonlacunar ischemic stroke incidence was positively associated with an
      orthostatic decrease of systolic and diastolic blood pressure, whereas greater
      lacunar stroke incidence was associated with both orthostatic increases and
      decreases in systolic blood pressure.

PMID- 21200000
TI  - The relationship between visit-to-visit variability in systolic blood pressure
      and all-cause mortality in the general population: findings from NHANES III, 1988
      to 1994.
AB  - Recent data suggest that visit-to-visit variability of blood pressure is
      associated with stroke incidence. Correlates of increased visit-to-visit
      variability in blood pressure and the relationship between variability and all
      cause mortality were examined using data on US adults >= 20 years of age from the
      Third National Health and Nutrition Examination Survey (n = 956). Three
      consecutive blood pressure readings were taken during 3 separate study visits
      from 1988 to 1994. Based on the mean of the second and third measurements from
      each visit, visit-to-visit blood pressure variability for each participant was
      defined using the standard deviation and coefficient of variation across visits.
      Mortality was assessed through December 31, 2006 (median follow-up = 14 years; n
      = 240 deaths). The mean of the standard deviation for systolic blood pressure
      across visits was 7.7 mm Hg. After multivariable adjustment, older age, female
      gender, history of myocardial infarction, higher mean systolic blood pressure and
      pulse pressure, and use of angiotensin converting enzyme inhibitors were
      associated with higher standard deviation in systolic blood pressure. The
      multivariable adjusted hazard ratios for all-cause mortality associated with a
      standard deviation of systolic blood pressure of 4.80 to 8.34 mm Hg and >= 8.35
      mm Hg, versus <4.80 mm Hg, were 1.57 (95% CI, 1.07 to 2.18) and 1.50 (95% CI,
      1.03 to 2.18), respectively. Results were similar when coefficient of variation
      for systolic blood pressure was evaluated. Visit-to-visit variability for
      diastolic blood pressure was not associated with mortality. In this population
      based study of US adults, higher levels of short-term visit-to-visit variability
      in systolic blood pressure were associated with increased all-cause mortality.

PMID- 21200002
TI  - Microvascular function predicts cardiovascular events in primary prevention: long
      term results from the Firefighters and Their Endothelium (FATE) study.
AB  - BACKGROUND: Biomarkers of atherosclerosis may refine clinical decision making in
      individuals at risk of cardiovascular disease. The purpose of the study was to
      determine the prognostic significance of endothelial function and other vascular
      markers in apparently healthy men. METHODS AND RESULTS: The cohort consisted of
      1574 men (age, 49.4 years) free of vascular disease. Measurements included flow
      mediated dilation and its microvascular stimulus, hyperemic velocity, carotid
      intima-media thickness, and C-reactive protein. Cox proportional hazard models
      evaluated the relationship between vascular markers, Framingham risk score, and
      time to a first composite cardiovascular end point of vascular death,
      revascularization, myocardial infarction, angina, and stroke. Subjects had low
      median Framingham risk score (7.9%). Cardiovascular events occurred in 71
      subjects (111 events) over a mean follow-up of 7.2+/-1.7 years. Flow-mediated
      dilation was not associated with subsequent cardiovascular events (hazard ratio,
      0.92; P=0.54). Both hyperemic velocity (hazard ratio, 0.70; 95% confidence
      interval, 0.54 to 0.90; P=0.006) and carotid intima-media thickness (hazard
      ratio, 1.45; confidence interval, 1.15 to 1.83; P=0.002) but not C-reactive
      protein (P=0.35) were related to events in a multivariable analysis that included
      Framingham risk score (per unit SD). Furthermore, the addition of hyperemic
      velocity to Framingham risk score resulted in a net clinical reclassification
      improvement of 28.7% (P<0.001) after 5 years of follow-up in the intermediate
      risk group. Overall net reclassification improvement for hyperemic velocity was
      6.9% (P=0.24). CONCLUSIONS: In men, hyperemic velocity, the stimulus for flow
      mediated dilation, but not flow-mediated dilation itself was a significant risk
      marker for adverse cardiovascular outcomes. The prognostic value was additive to
      traditional risk factors and carotid intima-media thickness. Hyperemic velocity,
      a newly described marker of microvascular function, is a novel tool that may
      improve risk stratification of lower-risk healthy men.

PMID- 21200001
TI  - Depot-specific differences and insufficient subcutaneous adipose tissue
      angiogenesis in human obesity.
AB  - BACKGROUND: Adipose tissue expands in response to excess caloric intake, but
      individuals prone to deposit visceral instead of subcutaneous adipose tissue have
      higher risk of metabolic disease. The role of angiogenesis in the expandability
      of human adipose tissue depots is unknown. The objective of this study was to
      measure angiogenesis in visceral and subcutaneous adipose tissue and to establish
      whether there is a relationship between obesity, metabolic status, and the
      angiogenic properties of these depots. METHODS AND RESULTS: Angiogenic capacity
      was determined by quantifying capillary branch formation from human adipose
      tissue explants embedded in Matrigel, and capillary density was assessed by
      immunohistochemistry. Subcutaneous adipose tissue had a greater angiogenic
      capacity than visceral tissue, even after normalization to its higher initial
      capillary density. Gene array analyses revealed significant differences in
      expression of angiogenic genes between depots, including an increased
      subcutaneous expression of angiopoietin-like protein 4, which is proangiogenic in
      an adipose tissue context. Subcutaneous capillary density and angiogenic capacity
      decreased with morbid obesity, and subcutaneous, but not visceral, adipose tissue
      angiogenic capacity correlated negatively with insulin sensitivity. CONCLUSIONS:
      These data imply that subcutaneous adipose tissue has a higher capacity to expand
      its capillary network than visceral tissue, but this capacity decreases with
      morbid obesity. The decrease correlates with insulin resistance, suggesting that
      impairment of subcutaneous adipose tissue angiogenesis may contribute to
      metabolic disease pathogenesis.

PMID- 21200003
TI  - Glucose-insulin-potassium: much more than enriched myocardial fuel.

PMID- 21200004
TI  - Glucose-insulin-potassium reduces the incidence of low cardiac output episodes
      after aortic valve replacement for aortic stenosis in patients with left
      ventricular hypertrophy: results from the Hypertrophy, Insulin, Glucose, and
      Electrolytes (HINGE) trial.
AB  - BACKGROUND: Patients undergoing aortic valve replacement for critical aortic
      stenosis often have significant left ventricular hypertrophy. Left ventricular
      hypertrophy has been identified as an independent predictor of poor outcome after
      aortic valve replacement as a result of a combination of maladaptive myocardial
      changes and inadequate myocardial protection at the time of surgery. Glucose
      insulin-potassium (GIK) is a potentially useful adjunct to myocardial protection.
      This study was designed to evaluate the effects of GIK infusion in patients
      undergoing aortic valve replacement surgery. METHODS AND RESULTS: Patients
      undergoing aortic valve replacement for aortic stenosis with evidence of left
      ventricular hypertrophy were randomly assigned to GIK or placebo. The trial was
      double-blind and conducted at a single center. The primary outcome was the
      incidence of low cardiac output syndrome. Left ventricular biopsies were analyzed
      to assess changes in 5' adenosine monophosphate-activated protein kinase (AMPK),
      Akt phosphorylation, and protein O-linked beta-N-acetylglucosamination (O
      GlcNAcylation). Over a 4-year period, 217 patients were randomized (107 control,
      110 GIK). GIK treatment was associated with a significant reduction in the
      incidence of low cardiac output state (odds ratio, 0.22; 95% confidence interval,
      0.10 to 0.47; P=0.0001) and a significant reduction in inotrope use 6 to 12 hours
      postoperatively (odds ratio, 0.30; 95% confidence interval, 0.15 to 0.60;
      P=0.0007). These changes were associated with a substantial increase in AMPK and
      Akt phosphorylation and a significant increase in the O-GlcNAcylation of selected
      protein bands. CONCLUSIONS: Perioperative treatment with GIK was associated with
      a significant reduction in the incidence of low cardiac output state and the need
      for inotropic support. This benefit was associated with increased signaling
      protein phosphorylation and O-GlcNAcylation. Multicenter studies and late follow
      up will determine whether routine use of GIK improves patient prognosis.

PMID- 21200005
TI  - Demise of open vein harvesting.

PMID- 21200006
TI  - Valve configuration determines long-term results after repair of the bicuspid
      aortic valve.
AB  - BACKGROUND: Reconstruction of the regurgitant bicuspid aortic valve has been
      performed for >10 years, but there is limited information on long-term results.
      We analyzed our results to determine the predictors of suboptimal outcome.
      METHODS AND RESULTS: Between November 1995 and December 2008, 316 patients (age,
      49+/-14 years; male, 268) underwent reconstruction of a regurgitant bicuspid
      aortic valve. Intraoperative assessment included extent of fusion, root
      dimensions, circumferential orientation of the 2 normal commissures (>160 degrees
      , <=160 degrees ), and effective height after repair. Cusp pathology was treated
      by central plication (n=277), triangular resection (n=138), or pericardial patch
      (n=94). Root dilatation was treated by subcommissural plication (n=100), root
      remodeling (n=122), or valve reimplantation (n=2). All patients were followed up
      echocardiographically (cumulative follow-up, 1253 years; mean, 4+/-3.1 years).
      Clinical and morphological parameters were analyzed for correlation with 10-year
      freedom from reoperation with the Cox proportional hazards model. Hospital
      mortality was 0.63%; survival was 92% at 10 years. Freedom from reoperation at 5
      and 10 years was 88% and 81%; freedom from valve replacement, 95% and 84%. By
      univariable analysis, statistically significant predictors of reoperation were
      age (hazard ratio [HR]=0.97), aortoventricular diameter (HR=1.24), effective
      height (HR=0.76), commissural orientation (HR=0.95), use of a pericardial patch
      (HR=7.63), no root replacement (HR=3.80), subcommissural plication (HR=2.07), and
      preoperative aortic regurgitation grade 3 or greater. By multivariable analysis,
      statistically significant predictors for reoperation were age (HR=0.96),
      aortoventricular diameter (HR=1.30), effective height (HR=0.74), commissural
      orientation (HR=0.96), and use of a pericardial patch (HR=5.16). CONCLUSIONS:
      Reconstruction of bicuspid aortic valve can be performed reproducibly with good
      early results. Recurrence and progression of regurgitation, however, may occur,
      depending primarily on anatomic features of the valve.

PMID- 21200007
TI  - Dabigatran versus warfarin in patients with atrial fibrillation: an analysis of
      patients undergoing cardioversion.
AB  - BACKGROUND: The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE
      LY) trial compared dabigatran 110 mg BID (D110) and 150 mg BID (D150) with
      warfarin for stroke prevention in 18 113 patients with nonvalvular atrial
      fibrillation. METHODS AND RESULTS: Cardioversion on randomized treatment was
      permitted. Precardioversion transesophageal echocardiography was encouraged,
      particularly in dabigatran-assigned patients. Data from before, during, and 30
      days after cardioversion were analyzed. A total of 1983 cardioversions were
      performed in 1270 patients: 647, 672, and 664 in the D110, D150, and warfarin
      groups, respectively. For D110, D150, and warfarin, transesophageal
      echocardiography was performed before 25.5%, 24.1%, and 13.3% of cardioversions,
      of which 1.8%, 1.2%, and 1.1% were positive for left atrial thrombi. Continuous
      treatment with study drug for >=3 weeks before cardioversion was lower in D110
      (76.4%) and D150 (79.2%) compared with warfarin (85.5%; P<0.01 for both). Stroke
      and systemic embolism rates at 30 days were 0.8%, 0.3%, and 0.6% (D110 versus
      warfarin, P=0.71; D150 versus warfarin, P=0.40) and similar in patients with and
      without transesophageal echocardiography. Major bleeding rates were 1.7%, 0.6%,
      and 0.6% (D110 versus warfarin, P=0.06; D150 versus warfarin, P=0.99).
      CONCLUSIONS: This study is the largest cardioversion experience to date and the
      first to evaluate a novel anticoagulant in this setting. The frequencies of
      stroke and major bleeding within 30 days of cardioversion on the 2 doses of
      dabigatran were low and comparable to those on warfarin with or without
      transesophageal echocardiography guidance. Dabigatran is a reasonable alternative
      to warfarin in patients requiring cardioversion.

PMID- 21200008
TI  - Mechanisms of atrial tachyarrhythmias associated with coronary artery occlusion
      in a chronic canine model.
AB  - BACKGROUND: Coronary artery disease predisposes to atrial fibrillation (AF), but
      the effects of chronic atrial ischemia/infarction on AF-related substrates are
      unknown. METHODS AND RESULTS: Regional right atrial myocardial infarction (MI)
      was created in 40 dogs by ligating an artery that supplies the right atrial free
      wall and not the ventricles; 35 sham dogs with the same artery isolated but not
      ligated were controls. Dogs were observed 8 days after MI and subjected to open
      chest study, in vitro optical mapping, and/or cell isolation for patch-clamp and
      Ca(2+) imaging on day 8. Holter ECGs showed more spontaneous atrial ectopy in MI
      dogs (eg, 662+/-281 on day 7 versus 34+/-25 ectopic complexes per day at
      baseline; 52+/-21 versus 1+/-1 atrial tachycardia episodes per day). Triggered
      activity was increased in MI border zone cells, which had faster decay of
      caffeine-evoked Ca(2+) transients and enhanced (by ~73%) Na(+)-Ca(2+) exchange
      current. Spontaneous Ca(2+) sparks (confocal microscopy) occurred under beta
      adrenergic stimulation in more MI dog cells (66+/-9%) than in control cells (29+/
      4%; P<0.01). Burst pacing induced long-lasting AF in MI dogs (1146+/-259 versus
      30+/-14 seconds in shams). Increased border zone conduction heterogeneity was
      confirmed by both bipolar electrode mapping in vivo and optical mapping. Optical
      mapping demonstrated stable border zone reentry in all 9 MI preparations but in
      none of 6 shams. Border zone tissue showed increased fibrous tissue content.
      CONCLUSIONS: Chronic atrial ischemia/infarction creates substrates for both
      spontaneous ectopy (Ca(2+)-release events, increased Na(+)-Ca(2+) exchange
      current) and sustained reentry (conduction abnormalities that anchor reentry).
      Thus, chronic atrial infarction in dogs promotes both AF triggers and the
      substrate for AF maintenance. These results provide novel insights into potential
      AF mechanisms in patients with coronary artery disease.

PMID- 21200009
TI  - Long-term outcome and impact of surgery on adults with coronary arteries
      originating from the opposite coronary cusp.
AB  - BACKGROUND: An anomalous coronary artery from the opposite sinus of Valsalva may
      increase sudden death risk in children and young adults, and surgical
      intervention is often recommended. The impact of this lesion when recognized in
      the adult and its management are ill defined. METHODS AND RESULTS: We reviewed
      210 700 cardiac catheterizations performed over a 35-year period at a single
      institution and identified 301 adults with an anomalous coronary artery from the
      opposite sinus of Valsalva, either anomalous right coronary artery from the left
      cusp or anomalous left main coronary artery from the right cusp. Patients were
      stratified by the pathway of the anomalous artery and the chosen treatment. Among
      the 301 patients with anomalous coronary artery from the opposite sinus of
      Valsalva (0.14% of the cohort), 79% had anomalous right coronary artery from the
      left cusp, and 18% had an interarterial course (IAC). Patients with IAC were
      younger (52+/-13 versus 59+/-13 years; P=0.001) and more likely to undergo
      surgical intervention (52% versus 27%; P<0.001), but mortality was not increased
      with IAC. Among the 54 patients with IAC, 28 underwent surgical repair with no
      perioperative deaths. Patients evaluated since 2000 were significantly more
      likely to be referred for surgery (P=0.004). Surgical patients were more likely
      to have abnormal stress tests (90% versus 43%; P=0.01) and had more extensive
      atherosclerosis but less diabetes mellitus (0% versus 23%; P=0.01). Long-term
      survival at 10 years appeared similar in both groups. CONCLUSIONS: In this single
      center cohort study of patients with an anomalous coronary artery from the
      opposite sinus of Valsalva, surgical management appears to have been favored
      recently. Despite no perioperative mortality, a positive impact on long-term
      survival was not observed. The impact of surgery in older adults with anomalous
      coronary arteries arising from the opposite coronary sinus with IAC deserves
      further study.

PMID- 21200010
TI  - Long-term outcomes of endoscopic vein harvesting after coronary artery bypass
      grafting.
AB  - BACKGROUND: Use of endoscopic saphenous vein harvesting has developed into a
      routine surgical approach at many cardiothoracic surgical centers. The
      association between this technique and long-term morbidity and mortality has
      recently been called into question. The present report describes the use of open
      versus endoscopic vein harvesting and risk of mortality and repeat
      revascularization in northern New England during a time period (2001 to 2004) in
      which both techniques were being performed. METHODS AND RESULTS: From 2001 to
      2004, 8542 patients underwent isolated coronary artery bypass grafting
      procedures, 52.5% with endoscopic vein harvesting. Surgical discretion dictated
      the vein harvest approach. The main outcomes were death and repeat
      revascularization (percutaneous coronary intervention or coronary artery bypass
      grafting) within 4 years of the index admission. The use of endoscopic vein
      harvesting increased from 34% in 2001 to 75% in 2004. In general, patients
      undergoing endoscopic vein harvesting had greater disease burden. Endoscopic vein
      harvesting was associated with an increased adjusted risk of bleeding requiring a
      return to the operating room (2.4 versus 1.7; P=0.03) but a decreased risk of leg
      wound infections (0.2 versus 1.1; P<0.001). Use of endoscopic vein harvesting was
      associated with a significant reduction in long-term mortality (adjusted hazard
      ratio, 0.74; 95% confidence interval, 0.60 to 0.92) but a nonsignificant
      increased risk of repeat revascularization (adjusted hazard ratio, 1.29; 95%
      confidence interval, 0.96 to 1.74). Similar results were obtained in propensity
      stratified analysis. CONCLUSIONS: During 2001 to 2004 in northern New England,
      the use of endoscopic vein harvesting was not associated with harm. There was a
      nonsignificant increase in repeat revascularization, and survival was not
      decreased.

PMID- 21200011
TI  - Multimodality cardiac imaging in the evaluation of mitral annular caseous
      calcification.

PMID- 21200012
TI  - Letter by Lippi and Cervellin regarding article, "High-sensitivity troponin T
      concentrations in acute chest pain patients evaluated with cardiac computed
      tomography".

PMID- 21200016
TI  - Clinical cardiology: physician update: erectile dysfunction and cardiovascular
      disease.

PMID- 21200015
TI  - Exercise rehabilitation in peripheral artery disease: functional impact and
      mechanisms of benefits.

PMID- 21200017
TI  - Rupture of an aneurysmal aortic diverticulum associated with coarctation and
      bicuspid aortic valve.

PMID- 21200018
TI  - COMP-Ang1 stimulates HIF-1alpha-mediated SDF-1 overexpression and recovers
      ischemic injury through BM-derived progenitor cell recruitment.
AB  - Recruitment and adhesion of bone marrow (BM)-derived circulating progenitor cells
      to ischemic tissue are important for vasculogenesis and tissue repair. Recently,
      we found cartilage oligomeric matrix protein (COMP)-Ang1 is a useful cell-priming
      agent to improve the therapeutic efficacy of progenitor cells. However, the
      effect and the underlying mechanisms of COMP-Ang1 on recruitment of BM-derived
      progenitor cells (BMPCs) to foci of vascular injury have not been well defined.
      Here, we found that COMP-Ang1 is a critical stimulator of stromal cell-derived
      factor 1 (SDF-1), the principal regulator of BM-cell trafficking. Furthermore,
      SDF-1 stimulation by COMP-Ang1 was blocked by small-interfering RNA (siRNA)
      against hypoxia-inducible factor-1alpha (HIF-1alpha). COMP-Ang1 increased the
      synthesis of HIF-1alpha by activating mammalian target of rapamycin (mTOR) in
      hypoxic endothelium. The intermediate mechanism transmitting the COMP-Ang1 signal
      to the downstream mTOR/HIF-1alpha/SDF-1 pathway was the enhanced binding of the
      Tie2 receptor with integrin-linked kinase (ILK), an upstream activator of mTOR.
      In the mouse ischemic model, local injection of COMP-Ang1 stimulated the
      incorporation of BMPCs into ischemic limb, thereby enhancing neovasculogenesis
      and limb salvage. Collectively, our findings identify the COMP-Ang1/HIF
      1alpha/SDF-1 pathway as a novel inducer of BMPC recruitment and neovasculogenesis
      in ischemic disease.

PMID- 21200019
TI  - Epigenetic control of IRF1 responses in HIV-exposed seronegative versus HIV
      susceptible individuals.
AB  - Not all individuals exposed to HIV become infected. Understanding why these HIV
      exposed seronegative individuals remain uninfected will help inform the
      development of preventative measures against HIV infection. Interferon regulatory
      factor-1 (IRF1) plays a critical role both in host antiviral immunity and in HIV
      1 replication. This study examined IRF1 expression regulation in the ex vivo
      peripheral blood mononuclear cells of HIV-exposed seronegative commercial sex
      workers who can be epidemiologically defined as relatively resistant to HIV
      infection (HIV-R), versus HIV-uninfected, susceptible controls (HIV-S). Whereas
      HIV-susceptible individuals demonstrated a biphasic, prolonged increase in IRF1
      expression after interferon-gamma stimulation, HIV-R individuals demonstrated a
      robust, but transient response. We also found that the IRF1 promoter in HIV-R was
      primed by increased basal histone deacetylase-2 binding, independently of
      transcription regulators, STAT1 and nuclear factor-kappaB/p65, implicating an
      epigenetic silencing mechanism. Interestingly, the transitory IRF1 response in
      HIV-R was sufficient in comparable regulation of interleukin-12 and interleukin-4
      expression compared with the HIV-susceptible controls. This is the first study
      characterizing IRF1 responsiveness in individuals who demonstrate altered
      susceptibility to HIV infection. These data suggest that transitory IRF1
      responsiveness in HIV-R may be one of the key contributors to the altered
      susceptibility to HIV infection during the early stages of primary HIV infection.

PMID- 21200020
TI  - N-Ras(G12D) induces features of stepwise transformation in preleukemic human
      umbilical cord blood cultures expressing the AML1-ETO fusion gene.
AB  - AML1-ETO (AE) is a fusion product of t(8;21) observed in 40% French-American
      British M2 type of acute myeloid leukemia (AML). Clinical data suggest that Ras
      mutation is a frequent cooperating event in t(8;21) AML. Whether constitutively
      active Ras promotes leukemogenesis on the t(8;21) background has not been
      demonstrated experimentally. Here, we retrovirally expressed N-Ras(G12D) in AE
      expressing human hematopoietic cells to investigate cooperativity. The AE/N
      Ras(G12D) cultures were cytokine-independent, enriched for CD34 positivity, and
      possessed increased colony-forming and replating abilities. N-Ras(G12D)
      expression led to Bcl-2 up-regulation and reduced apoptosis. Ectopic Bcl-2
      expression also resulted in enhanced colony-forming and replating abilities but
      was insufficient to sustain cytokine independence. AE/N-Ras(G12D) cells were more
      sensitive to Bcl-2 inhibition with ABT-737 than parent AE cells. Enhanced
      engraftment of AE/N-Ras(G12D) cells was observed on intrafemoral injection into
      immunodeficient mice, presumably because of improved survival in the bone marrow
      microenvironment. N-Ras(G12D) promotes progression toward transformation in AE
      expressing cells, partially through up-regulating Bcl-2.

PMID- 21200021
TI  - HIV disease progression correlates with the generation of dysfunctional naive
      CD8(low) T cells.
AB  - HIV infection can result in depletion of total CD4(+) T cells and naive CD8(+) T
      cells, and in the generation of dysfunctional effector CD8(+) T cells. In this
      study, we show that naive CD8(+) T cells in subjects with progressive HIV disease
      express low levels of CD8alpha and CD8beta chains. Such naive CD8(low) T cells
      display broad signaling defects across the T-cell receptor complex, and their
      appearance correlates with generalized up-regulation of major histocompatibility
      complex class I (MHC-I) antigens on peripheral blood mononuclear cells (PBMCs).
      To explore a causal link between increased MHC-I up-regulation and the generation
      of naive CD8(low) T cells, we used the humanized SCID-hu Thy/Liv mouse model to
      show that HIV infection of the thymus and interferon alpha (IFNalpha) treatment
      alone result in MHC-I up-regulation and in the generation of dysfunctional
      CD3(high)CD8(+)CD4(-) single-positive 8 (SP8) thymocytes with low expression of
      CD8. We suggest that dysfunctional naive CD8(low) T cells are generated as a
      result of IFNalpha-mediated up-regulation of MHC-I on stromal cells in the thymus
      and antigen-presenting cells in the periphery, and that dysfunction in this naive
      compartment contributes to the immunodeficiency of HIV disease. This study is
      registered at www.clinicaltrials.gov as NCT00187512.

PMID- 21200022
TI  - The integrin LFA-1 signals through ZAP-70 to regulate expression of high-affinity
      LFA-1 on T lymphocytes.
AB  - The integrin lymphocyte function-associated antigen 1 (LFA-1) controls many
      functions of T lymphocytes and is particularly essential during lymphocyte
      migration from blood into tissues. LFA-1 is considered to initiate "outside-in"
      signaling when bound to ligand intercellular adhesion molecule 1 (ICAM-1), but
      little is known about the proteins involved or where in the cell such LFA-1
      mediated signaling might be operating. Here we show that LFA-1 is constitutively
      associated with the protein tyrosine kinases Lck and zeta chain-associated
      protein of 70 kDa (ZAP-70). When LFA-1 binds ICAM-1, both kinases become
      phosphorylated and the consequence of kinase activation is the conversion of
      intermediate- to high-affinity LFA-1 and an increase in close contact with ICAM
      1. In the polarized T lymphocyte, phospho-ZAP-70 is concentrated within a region
      of high-affinity LFA-1 that includes talin and encompasses the
      lamella/lamellipodial interface as well as further back in the cell. Deficiency
      of ZAP-70 through inhibition or knockdown in T lymphocytes decreases the speed of
      migration on ICAM-1, as well as reducing firm adhesion under shear-flow
      conditions. Through its control of high-affinity LFA-1, the LFA-1/Lck/ZAP-70
      complex is in position to initiate the rapid adhesion strengthening and migration
      necessary for T-lymphocyte responses when stimulated vasculature is encountered
      at sites of infection or injury.

PMID- 21200023
TI  - Identification of microRNAs in the cerebrospinal fluid as marker for primary
      diffuse large B-cell lymphoma of the central nervous system.
AB  - The diagnosis of primary central nervous system lymphoma (PCNSL) depends on
      histopathology of brain biopsies, because disease markers in the cerebrospinal
      fluid (CSF) with sufficient diagnostic accuracy are not available yet. MicroRNAs
      (miRNAs) are regulatory RNA molecules that are deregulated in many disease types,
      including cancer. Recently, miRNAs have shown promise as markers for cancer
      diagnosis. In this study, we demonstrate that miRNAs are present in the CSF of
      patients with PCNSL. With a candidate approach and miRNA quantification by
      reverse transcription polymerase chain reaction, miRNAs with significant levels
      in the CSF of patients with PCNSL were identified. MiR-21, miR-19, and miR-92a
      levels in CSF collected from patients with PCNSL and from controls with
      inflammatory CNS disorders and other neurologic disorders indicated a significant
      diagnostic value of this method. Receiver-operating characteristic analyses
      showed area under the curves of 0.94, 0.98, and 0.97, respectively, for miR-21,
      miR-19, and miR-92a CSF levels in discriminating PCNSL from controls. More
      importantly, combined miRNA analyses resulted in an increased diagnostic accuracy
      with 95.7% sensitivity and 96.7% specificity. We also demonstrated a remarkable
      stability of miRNAs in the CSF. In conclusion, CSF miRNAs are potentially useful
      tools as novel noninvasive biomarker for the diagnosis of PCNSL.

PMID- 21200024
TI  - How I treat myelofibrosis.
AB  - It is currently assumed that myelofibrosis (MF) originates from acquired
      mutations that target the hematopoietic stem cell and induce dysregulation of
      kinase signaling, clonal myeloproliferation, and abnormal cytokine expression.
      These pathogenetic processes are interdependent and also individually
      contributory to disease phenotype-bone marrow stromal changes, extramedullary
      hematopoiesis, ineffective erythropoiesis, and constitutional symptoms. Molecular
      pathogenesis of MF is poorly understood despite a growing list of resident
      somatic mutations that are either functionally linked to Janus kinase (JAK)
      signal transducer and activator of transcription hyperactivation (eg JAK2, MPL,
      and LNK mutations) or possibly involved in epigenetic dysregulation of
      transcription (TET2, ASXL1, or EZH2 mutations). Current prognostication in
      primary MF is based on the Dynamic International Prognostic Scoring System-plus
      model, which uses 8 independent predictors of inferior survival to classify
      patients into low, intermediate 1, intermediate 2, and high-risk disease groups;
      corresponding median survivals are estimated at 15.4, 6.5, 2.9, and 1.3 years.
      Such information is used to plan a risk-adapted treatment strategy for the
      individual patient, which might include observation alone, conventional or
      investigational (eg, JAK inhibitors, pomalidomide) drug therapy, allogenic stem
      cell transplantation with reduced- or conventional-intensity conditioning,
      splenectomy, or radiotherapy. I discuss these treatment approaches in the context
      of who should get what and when.

PMID- 21200025
TI  - Comparative effectiveness of ductal carcinoma in situ management and the roles of
      margins and surgeons.
AB  - BACKGROUND: The high incidence of ductal carcinoma in situ (DCIS) and variations
      in its treatment motivate inquiry into the comparative effectiveness of treatment
      options. Few such comparative effectiveness studies of DCIS, however, have been
      performed with detailed information on clinical and treatment attributes.
      METHODS: We collected detailed clinical, nonclinical, pathological, treatment,
      and long-term outcomes data from multiple medical records of 994 women who were
      diagnosed with DCIS from 1985 through 2000 in Monroe County (New York) and the
      Henry Ford Health System (Detroit, MI). We used ipsilateral disease-free survival
      models to characterize the role of treatments (surgery and radiation therapy) and
      margin status (positive, close [<2 mm], or negative [>=2 mm]) and logistic
      regression models to characterize the determinants of treatments and margin
      status, including the role of surgeons. All statistical tests were two-sided.
      RESULTS: Treatments and margin status were statistically significant and strong
      predictors of long-term disease-free survival, but results varied substantially
      by surgeon. This variation by surgeon accounted for 15%-35% of subsequent
      ipsilateral 5-year recurrence rates and for 13%-30% of 10-year recurrence rates.
      The overall differences in predicted 5-year disease-free survival rates for
      mastectomy (0.993), breast-conserving surgery with radiation therapy (0.945), and
      breast-conserving surgery without radiation therapy (0.824) were statistically
      significant (P(diff) < .001 for each of the differences). Similarly, each of the
      differences at 10 years was statistically significant (P < .001). CONCLUSIONS:
      Our work demonstrates the contributions of treatments and margin status to long
      term ipsilateral disease-free survival and the link between surgeons and these
      key measures of care. Although variation by surgeon could be generated by
      patients' preferences, the extent of variation and its contribution to long-term
      health outcomes are troubling. Further work is required to determine why women
      with positive margins receive no additional treatment and why margin status and
      receipt of radiation therapy vary by surgeon.

PMID- 21200026
TI  - Random physician effect and comparative effectiveness of treatment for ductal
      carcinoma in situ.

PMID- 21200027
TI  - Su(dx) E3 ubiquitin ligase-dependent and -independent functions of polychaetoid,
      the Drosophila ZO-1 homologue.
AB  - Zona occludens (ZO) proteins are molecular scaffolds localized to cell junctions,
      which regulate epithelial integrity in mammals. Using newly generated null
      alleles, we demonstrate that polychaetoid (pyd), the unique Drosophila
      melanogaster ZO homologue, regulates accumulation of adherens junction-localized
      receptors, such as Notch, although it is dispensable for epithelial polarization.
      Pyd positively regulates Notch signaling during sensory organ development but
      acts negatively on Notch to restrict the ovary germline stem cell niche. In both
      contexts, we identify a core antagonistic interaction between Pyd and the WW
      domain E3 ubiquitin ligase Su(dx). Pyd binds Su(dx) directly, in part through a
      noncanonical WW-binding motif. Pyd also restricts epithelial wing cell numbers to
      control adult wing shape, a function associated with the FERM protein Expanded
      and independent of Su(dx). As both Su(dx) and Expanded regulate trafficking, we
      propose that a conserved role of ZO proteins is to coordinate receptor
      trafficking and signaling with junctional organization.

PMID- 21200028
TI  - Heparan sulfate proteoglycan syndecan-3 is a novel receptor for GDNF, neurturin,
      and artemin.
AB  - Glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) are
      potent survival factors for dopaminergic neurons and motoneurons with therapeutic
      potential for Parkinson's disease. Soluble GFLs bind to a ligand-specific
      glycosylphosphatidylinositol-anchored coreceptor (GDNF family receptor alpha) and
      signal through the receptor tyrosine kinase RET. In this paper, we show that all
      immobilized matrix-bound GFLs, except persephin, use a fundamentally different
      receptor. They interact with syndecan-3, a transmembrane heparan sulfate (HS)
      proteoglycan, by binding to its HS chains with high affinity. GFL-syndecan-3
      interaction mediates both cell spreading and neurite outgrowth with the
      involvement of Src kinase activation. GDNF promotes migration of cortical neurons
      in a syndecan-3-dependent manner, and in agreement, mice lacking syndecan-3 or
      GDNF have a reduced number of cortical gamma-aminobutyric acid-releasing neurons,
      suggesting a central role for the two molecules in cortical development.
      Collectively, syndecan-3 may directly transduce GFL signals or serve as a
      coreceptor, presenting GFLs to the signaling receptor RET.

PMID- 21200029
TI  - A novel fast mechanism for GPCR-mediated signal transduction--control of
      neurotransmitter release.
AB  - Reliable neuronal communication depends on accurate temporal correlation between
      the action potential and neurotransmitter release. Although a requirement for
      Ca(2+) in neurotransmitter release is amply documented, recent studies have shown
      that voltage-sensitive G protein-coupled receptors (GPCRs) are also involved in
      this process. However, how slow-acting GPCRs control fast neurotransmitter
      release is an unsolved question. Here we examine whether the recently discovered
      fast depolarization-induced charge movement in the M(2)-muscarinic receptor
      (M(2)R) is responsible for M(2)R-mediated control of acetylcholine release. We
      show that inhibition of the M(2)R charge movement in Xenopus oocytes correlated
      well with inhibition of acetylcholine release at the mouse neuromuscular
      junction. Our results suggest that, in addition to Ca(2+) influx, charge movement
      in GPCRs is also necessary for release control.

PMID- 21200030
TI  - Correlated fluorescence and 3D electron microscopy with high sensitivity and
      spatial precision.
AB  - Correlative electron and fluorescence microscopy has the potential to elucidate
      the ultrastructural details of dynamic and rare cellular events, but has been
      limited by low precision and sensitivity. Here we present a method for direct
      mapping of signals originating from ~20 fluorescent protein molecules to 3D
      electron tomograms with a precision of less than 100 nm. We demonstrate that this
      method can be used to identify individual HIV particles bound to mammalian cell
      surfaces. We also apply the method to image microtubule end structures bound to
      mal3p in fission yeast, and demonstrate that growing microtubule plus-ends are
      flared in vivo. We localize Rvs167 to endocytic sites in budding yeast, and show
      that scission takes place halfway through a 10-s time period during which
      amphiphysins are bound to the vesicle neck. This new technique opens the door for
      direct correlation of fluorescence and electron microscopy to visualize cellular
      processes at the ultrastructural scale.

PMID- 21200032
TI  - Summaries for patients: Protection against colorectal cancer with colonoscopy.

PMID- 21200031
TI  - IGF-II is regulated by microRNA-125b in skeletal myogenesis.
AB  - MicroRNAs (miRNAs) have emerged as key regulators of skeletal myogenesis, but our
      knowledge of the identity of the myogenic miRNAs and their targets remains
      limited. In this study, we report the identification and characterization of a
      novel myogenic miRNA, miR-125b. We find that the levels of miR-125b decline
      during myogenesis and that miR-125b negatively modulates myoblast differentiation
      in culture and muscle regeneration in mice. Our results identify IGF-II (insulin
      like growth factor 2), a critical regulator of skeletal myogenesis, as a direct
      and major target of miR-125b in both myocytes and regenerating muscles, revealing
      for the first time an miRNA mechanism controlling IGF-II expression. In addition,
      we provide evidence suggesting that miR-125b biogenesis is negatively controlled
      by kinase-independent mammalian target of rapamycin (mTOR) signaling both in
      vitro and in vivo as a part of a dual mechanism by which mTOR regulates the
      production of IGF-II, a master switch governing the initiation of skeletal
      myogenesis.

PMID- 21200033
TI  - In the clinic. Transient ischemic attack.
AB  - This issue provides a clinical overview of transient ischemic attack 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- 21200034
TI  - Using proteinuria and estimated glomerular filtration rate to classify risk in
      patients with chronic kidney disease: a cohort study.
AB  - BACKGROUND: The staging system for chronic kidney disease relies almost
      exclusively on estimated glomerular filtration rate (eGFR), although proteinuria
      is also associated with adverse outcomes. OBJECTIVE: To validate a 5-category
      system for risk stratification based on the combination of eGFR and proteinuria.
      DESIGN: Retrospective cohort study. SETTING: A provincial laboratory registry in
      Alberta, Canada, and a representative sample of noninstitutionalized U.S. adults.
      PATIENTS: A derivation data set of 474 521 adult outpatients, 2 independent
      internal validation cohorts with 51 356 and 460 623 patients, and an external
      validation cohort of 14 358 patients. MEASUREMENTS: Glomerular filtration rate,
      estimated by using the Modification of Diet in Renal Disease Study equation, and
      proteinuria, measured by using urine albumin-to-creatinine ratio or dipstick
      urinalysis. Outcomes included all-cause mortality and a composite renal outcome
      of kidney failure or doubling of serum creatinine level. RESULTS: Over a median
      follow-up of 38 months in the internal validation cohorts, higher risk categories
      (indicating lower eGFR or more proteinuria) were associated with a graded
      increase in the risk for the composite renal outcome. The projected number of
      U.S. adults assigned to risk categories 3 and 4 in the alternate system was 3.9
      million, compared with 16.3 million assigned to stage 3 and 4 in the current
      staging system. The alternate system was more likely to correctly reclassify
      persons who did not develop the renal outcome than those who did, although some
      persons developed the renal outcome despite reclassification to a lower category.
      However, all analyses of patients reclassified to a lower category showed that
      substantially fewer such patients developed the renal outcome than did not.
      Correct reclassification by the alternate system was more likely when proteinuria
      was measured by using albumin-to-creatinine ratio than with dipstick testing, and
      also more likely for the composite renal outcome than for mortality. LIMITATION:
      The study had a short follow-up time. CONCLUSION: Using proteinuria in
      combination with eGFR may reduce unnecessary referrals for care at the cost of
      not referring or delaying referral for some patients who go on to develop kidney
      failure. PRIMARY FUNDING SOURCE: Alberta Heritage Foundation for Medical Research
      interdisciplinary research team grant.

PMID- 21200035
TI  - Protection from colorectal cancer after colonoscopy: a population-based, case
      control study.
AB  - BACKGROUND: Colonoscopy with detection and removal of adenomas is considered a
      powerful tool to reduce colorectal cancer (CRC) incidence. However, the degree of
      protection achievable in a population setting with high-quality colonoscopy
      resources remains to be quantified. OBJECTIVE: To assess the association between
      previous colonoscopy and risk for CRC. DESIGN: Population-based case-control
      study. SETTING: Rhine-Neckar region of Germany. PATIENTS: A total of 1688 case
      patients with colorectal cancer and 1932 control participants aged 50 years or
      older. MEASUREMENTS: A detailed lifetime history of CRC risk factors and
      preventive factors, including history and results of previous colonoscopies, and
      of medical data obtained by self-reports and medical records. Odds ratios of CRC
      associated with colonoscopy in the preceding 10 years were estimated, after
      adjustment for sex, age, education level, participation in a general health
      screening examination, family history of CRC, smoking status, body mass index,
      and use of nonsteroidal anti-inflammatory drugs or hormone replacement therapy.
      RESULTS: Overall, colonoscopy in the preceding 10 years was associated with 77%
      lower risk for CRC. Adjusted odds ratios for any CRC, right-sided CRC, and left
      sided CRC were 0.23 (95% CI, 0.19 to 0.27), 0.44 (CI, 0.35 to 0.55), and 0.16
      (CI, 0.12 to 0.20), respectively. Strong risk reduction was observed for all
      cancer stages and all ages, except for right-sided cancer in persons aged 50 to
      59 years. Risk reduction increased over the years in both the right and the left
      colon. LIMITATION: The study was observational, with potential for residual
      confounding and selection bias. CONCLUSION: Colonoscopy with polypectomy can be
      associated with strongly reduced risk for CRC in the population setting. Aside
      from strong risk reduction with respect to left-sided CRC, risk reduction of more
      than 50% was also seen for right-sided colon cancer. PRIMARY FUNDING SOURCE:
      German Research Council and German Federal Ministry of Education and Research.

PMID- 21200036
TI  - Combined prednisone and mycophenolate mofetil treatment for retroperitoneal
      fibrosis: a case series.
AB  - BACKGROUND: Small case series suggest that a combination of mycophenolate mofetil
      and prednisone may be an effective treatment for patients with retroperitoneal
      fibrosis. OBJECTIVE: To describe the outcomes of adults with retroperitoneal
      fibrosis who received a combination of prednisone and mycophenolate mofetil.
      DESIGN: Prospective case series of patients followed between 1 April 2005 and 1
      July 2009. SETTING: Single tertiary care facility. PATIENTS: 28 patients with
      retroperitoneal fibrosis. INTERVENTION: Prednisone, 40 mg/d, tapered over 6
      months, and mycophenolate mofetil, 1000 mg twice daily, for a mean of 24.3
      months. MEASUREMENTS: Clinical course, laboratory assessment, and measurement of
      periaortic mass. Mean follow-up was 1012 days, and no patients were lost to
      follow-up. RESULTS: Systemic symptoms resolved in all patients; 89% had a 25% or
      greater reduction in periaortic mass. Elevated erythrocyte sedimentation rate and
      serum creatinine level and decreased hemoglobin level normalized in all patients.
      Disease recurred in 2 of 28 patients. LIMITATION: This was a small case series.
      CONCLUSION: Combined prednisone and mycophenolate mofetil therapy is a
      potentially effective treatment for retroperitoneal fibrosis that warrants
      evaluation in randomized trials. PRIMARY FUNDING SOURCE: None.

PMID- 21200037
TI  - Systematic review: Anti-epidermal growth factor receptor treatment effect
      modification by KRAS mutations in advanced colorectal cancer.
AB  - BACKGROUND: KRAS mutations have been extensively investigated as predictive
      biomarkers for treatment of advanced colorectal cancer with the anti-epidermal
      growth factor receptor (EGFR) antibodies cetuximab and panitumumab. PURPOSE: To
      summarize whether KRAS mutation status modifies effects of anti-EGFR-based
      treatments for patients with advanced colorectal cancer and whether KRAS status
      predicts clinical outcomes among such patients. DATA SOURCES: MEDLINE and 2
      curated genetics databases (through 24 March 2010) were searched for
      observational studies. MEDLINE, the Cochrane Central Register of Controlled
      Trials, the Cochrane Database of Systematic Reviews, and the Database of
      Abstracts of Reviews of Effects (through 1 September 2010) were searched for
      randomized, controlled trials. No search was restricted by language. STUDY
      SELECTION: Three reviewers screened titles and abstracts to identify published
      studies assessing KRAS mutations as predictors of overall and progression-free
      survival or treatment failure for patients who received anti-EGFR-based therapy
      for metastatic colorectal cancer. DATA EXTRACTION: Three investigators extracted
      data on population and study-design characteristics, including quality items, and
      on outcomes of interest. Random-effects meta-analyses were done on nonoverlapping
      studies. DATA SYNTHESIS: In 4 reanalyses of randomized trials of anti-EGFR-based
      therapy versus best supportive care or cytotoxic chemotherapy, no significant
      benefit was found for overall or progression-free survival from anti-EGFR-based
      treatment among KRAS-positive patients (hazard ratio [HR], 1.0). However,
      evidence favors anti-EGFR therapy among KRAS wild-type patients; the relative HR
      across KRAS-positive and wild-type patients was 1.30 (95% CI, 0.95 to 1.78) for
      overall survival and 2.22 (CI, 1.74 to 2.84) for progression-free survival by
      random-effects meta-analysis. In 13 cohorts of patients who received anti-EGFR
      antibodies, the summary HR for overall survival was 1.79 (CI, 1.48 to 2.17), with
      better survival in wild-type patients. The corresponding HR for progression-free
      survival was 2.11 (CI, 1.74 to 2.55 [16 cohorts]). In random-effects bivariate
      meta-analysis of 22 studies, the summary sensitivity of KRAS mutations for
      predicting lack of response was 0.49 (CI, 0.43 to 0.55), and summary specificity
      was 0.93 (CI, 0.87 to 0.97). LIMITATIONS: Limited evidence from randomized
      studies exists. Patient-level data are needed to assess modifiers of the mutation
      by-treatment interaction. Publication bias could be a concern. CONCLUSION: KRAS
      mutations are consistently associated with reduced overall and progression-free
      survival and increased treatment failure rates among patients with advanced
      colorectal cancer treated with anti-EGFR antibodies. PRIMARY FUNDING SOURCE:
      Agency for Healthcare Research and Quality.

PMID- 21200038
TI  - A systematic examination of the citation of prior research in reports of
      randomized, controlled trials.
AB  - BACKGROUND: A randomized, controlled trial (RCT) should not be started or
      interpreted without accounting for evidence from preceding RCTs addressing the
      same question. Research has suggested that evidence from prior trials is often
      not accounted for in reports of subsequent RCTs. OBJECTIVE: To assess the extent
      to which reports of RCTs cite prior trials studying the same interventions.
      DESIGN: Meta-analyses published in 2004 that combined 4 or more trials were
      identified; within each meta-analysis, the extent to which each trial report
      cited the trials that preceded it by more than 1 year was assessed. MEASUREMENTS:
      The proportion of prior trials that were cited (prior research citation index),
      the proportion of the total participants from prior trials that were in the cited
      trials (sample size citation index), and the absolute number of trials cited were
      calculated. RESULTS: 227 meta-analyses were identified, comprising 1523 trials
      published from 1963 to 2004. The median prior research citation index was 0.21
      (95% CI, 0.18 to 0.24), meaning that less than one quarter of relevant reports
      were cited. The median sample size citation index (0.24 [CI, 0.21 to 0.27]) was
      similar, suggesting that larger trials were not selectively cited. Of the 1101
      RCTs that had 5 or more prior trials to cite, 254 (23%) cited no prior RCTs and
      257 (23%) cited only 1. The median number of prior cited trials was 2, which did
      not change as the number of citable trials increased. The mean number of
      preceding trials cited by trials published after 2000 was 2.4, compared with 1.5
      for those published before 2000 (P < 0.001). LIMITATION: The investigators could
      not ascertain why prior trials were not cited, and noncited trials may have been
      taken into account in the trial design and proposal stages. CONCLUSION: In
      reports of RCTs published over 4 decades, fewer than 25% of preceding trials were
      cited, comprising fewer than 25% of the participants enrolled in all relevant
      prior trials. A median of 2 trials was cited, regardless of the number of prior
      trials that had been conducted. Research is needed to explore the explanations
      for and consequences of this phenomenon. Potential implications include ethically
      unjustifiable trials, wasted resources, incorrect conclusions, and unnecessary
      risks for trial participants. PRIMARY FUNDING SOURCE: None.

PMID- 21200039
TI  - Integrating addiction medicine into graduate medical education in primary care:
      the time has come.
AB  - Substance use disorders create an enormous burden of medical, behavioral, and
      social problems and pose a major and costly public health challenge. Despite the
      high prevalence of substance use and its consequences, physicians often do not
      recognize these conditions and, as a result, provide inadequate patient care. At
      the center of this failure is insufficient training for physicians about
      substance use disorders. To address this deficit, the Betty Ford Institute
      convened a meeting of experts who developed the following 5 recommendations
      focused on improving training in substance abuse in primary care residency
      programs in internal medicine and family medicine: 1) integrating substance abuse
      competencies into training, 2) assigning substance abuse teaching the same
      priority as teaching about other chronic diseases, 3) enhancing faculty
      development, 4) creating addiction medicine divisions or programs in academic
      medical centers, and 5) making substance abuse screening and management routine
      care in new models of primary care practice. This enhanced primary care residency
      training should represent a major step forward in improving patient care.

PMID- 21200040
TI  - Welcome to the patient-centered medical neighborhood.

PMID- 21200041
TI  - The patient-centered medical home neighbor: A primary care physician's view.
AB  - The American College of Physicians' position paper on the patient-centered
      medical home neighbor (PCMH-N) extends the work of the patient-centered medical
      home (PCMH) as a means of improving the delivery of health care. Recognizing that
      the PCMH does not exist in isolation, the PCMH-N concept outlines expectations
      for comanagement, communication, and care coordination and broadens
      responsibility for safe, effective, and efficient care beyond primary care to
      include physicians of all specialties. As such, it is a fitting follow-up to the
      PCMH and moves further down the road toward improved care for complex patients.
      Yet, there is more work to be done. Truly transforming the U.S. health care
      system around personalized medical homes embedded in highly functional medical
      neighborhoods will require better staffing models; more robust electronic
      information tools; aligned incentives for quality and efficiency within payment
      and regulatory policies; and a culture of greater engagement of patients, their
      families, and communities.

PMID- 21200042
TI  - The patient-centered medical home neighbor: A subspecialty physician's view.
AB  - To achieve the benefits of the patient-centered medical home (PCMH) model, the
      American College of Physicians has issued a policy paper addressing the
      relationship between specialist and subspecialist physicians and PCMH practices.
      This paper represents a significant step toward improving care coordination and
      quality by demonstrating that this model is supported by numerous specialties and
      subspecialties, recognizing the importance of building a strong medical
      neighborhood, and providing a framework that will foster improvements in care at
      the interface of PCMHs and PCMH neighbors (PCMH-Ns). Construction of a well
      functioning medical neighborhood will, however, require some refinements. First,
      the proposed interaction typology between PCMHs and PCMH-Ns must be expanded to
      include innovative forms of interaction that do not depend on traditional office
      visits, but for which there are clear incentives. Second, the recommended care
      coordination agreements must be better standardized for the sake of practicality.
      Finally, genuine dialogue between PCMH and PCMH-N practices needs to be realized.

PMID- 21200043
TI  - Classification of chronic kidney disease: a step forward.

PMID- 21200044
TI  - Colonoscopy: what does it take to get it "right"?

PMID- 21200045
TI  - In praise of the cognitive specialist.

PMID- 21200046
TI  - Candidate performance measures for screening for, assessing, and treating
      unhealthy substance use in hospitals.

PMID- 21200047
TI  - Candidate performance measures for screening for, assessing, and treating
      unhealthy substance use in hospitals.

PMID- 21200048
TI  - Candidate performance measures for screening for, assessing, and treating
      unhealthy substance use in hospitals.

PMID- 21200049
TI  - Antiviral prescribing by office-based physicians during the 2009 H1N1 pandemic.

PMID- 21200050
TI  - Children's hospitals gain legislative victory on 340B orphan drugs: Newly
      eligible hospitals still denied discounts.

PMID- 21200051
TI  - Health care reform means challenges, opportunities in rural areas.

PMID- 21200052
TI  - ASHP, APhA warn of decreased graduate quality from increased enrollments.

PMID- 21200053
TI  - Moving antimicrobial stewardship from restriction to facilitation.

PMID- 21200054
TI  - Managing the residency scramble.

PMID- 21200055
TI  - Job satisfaction in hospital pharmacists.

PMID- 21200056
TI  - Writing a personal philosophy of practice.

PMID- 21200057
TI  - Is double coverage of gram-negative organisms necessary?
AB  - PURPOSE: The appropriateness of combination therapy for infections caused by gram
      negative organisms is examined. SUMMARY: Mortality from Pseudomonas aeruginosa
      infection is particularly high; therefore, empirical regimens are often selected
      to ensure coverage for this organism. The initial use of combination
      antimicrobial therapy for gram-negative infections is usually justified by one of
      three reasons: the potential for synergistic activity between two classes of
      antimicrobial agents, the broad empirical coverage provided by two antimicrobial
      agents with differing spectra of activity and resistance patterns, or the
      prevention of resistance development during antimicrobial therapy. Disadvantages
      of using combination therapy are increased drug toxicity, increased costs, and
      increased risk of superinfection with more-resistant bacteria or fungi. There are
      no clinical data that suggest that the combination of a beta-lactam plus a
      fluoroquinolone results in improved patient outcomes compared with a beta-lactam
      alone or a beta-lactam plus an aminoglycoside. Results from studies that evaluate
      combination therapy versus monotherapy for gram-negative bacilli conflict with
      the common practice of use of double coverage. Strong evidence to support the
      administration of antimicrobials for double coverage of gram-negative organisms
      is lacking. Antimicrobial overuse may lead to antibiotic resistance, unnecessary
      adverse effects, and increased costs. CONCLUSION: The available clinical evidence
      does not support the routine use of combination antimicrobial therapy for
      treatment of gram-negative infections. Patients with shock or neutropenia may
      benefit from combination therapy that includes an aminoglycoside.

PMID- 21200058
TI  - Treatment of local-anesthetic toxicity with lipid emulsion therapy.
AB  - PURPOSE: The use of lipid emulsion to treat local-anesthetic toxicity is
      discussed. SUMMARY: Systemic toxicity from local anesthetics is a rare but
      potentially fatal complication of regional anesthesia. There is increasing
      evidence that lipid emulsion may be an effective treatment to reverse the cardiac
      and neurologic effects of local-anesthetic toxicity. A literature search
      identified seven case reports of local-anesthetic toxicity in which lipid
      emulsion was used. Lipid emulsion was found to be successful in the treatment of
      local-anesthetic toxicity associated with various regional anesthetic techniques
      and multiple local anesthetics. The majority of patients in the case reports
      reviewed were unresponsive to initial management of local-anesthetic toxicity
      with standard resuscitative measures, but all recovered completely after
      receiving lipid emulsion therapy. The initial dose of lipid emulsion administered
      varied among the case reports, as well as whether a lipid emulsion infusion was
      started and at what point during resuscitation. Based on the case reports
      reviewed, an initial bolus dose of 1.5 mL/kg followed by an infusion of 10 mL/min
      as soon as local-anesthetic toxicity is suspected seems most beneficial. The
      pharmacokinetics of lipid emulsion therapy in the treatment of local-anesthetic
      toxicity has not been fully elucidated but likely involves increasing metabolism,
      distribution, or partitioning of the local anesthetic away from receptors into
      lipid within tissues. CONCLUSION: Lipid emulsion has been reported useful in the
      treatment of systemic toxicity caused by local anesthetics. The mechanism of
      effect is unclear, and evidence for the benefit of lipid therapy in humans is
      from case reports only.

PMID- 21200059
TI  - Phentolamine continuous infusion in a patient with pheochromocytoma.
AB  - PURPOSE: Use of continuous phentolamine infusion therapy for management of
      serious cardiovascular complications during adrenalectomy for pheochromocytoma is
      reported. SUMMARY: In preparation for surgical resection of a pheochromocytoma, a
      38-year-old woman received outpatient oral therapy with the alpha-adrenergic
      receptor blocker phenoxybenzamine for 25 days with the goal of reducing
      cardiovascular risks associated with catecholamine surge during surgery. Due to
      inappropriate dosage adjustment, however, outpatient phenoxybenzamine therapy did
      not achieve adequate alpha-adrenergic-receptor blockade; during the laparoscopic
      resection procedure, the woman developed severe hypertension, leading to cardiac
      arrest and discontinuation of the operation. After resuscitative measures, the
      patient was admitted to the surgical intensive care unit for mechanical
      ventilation, medical management (including intermittent bolus injections of
      phentolamine and a continuous i.v. infusion of esmolol for control of blood
      pressure and heart rate), and hemodynamic monitoring; despite those measures,
      cardiovascular instability persisted during the immediate postoperative period.
      The day after the abortive surgery attempt, a continuous infusion of phentolamine
      mesylate (1 mg/hr, adjusted hourly to achieve the blood pressure target) was
      initiated. Four days after initiation of continuous phentolamine infusion, the
      patient was deemed to be hemodynamically stable, and the surgery was successfully
      performed. CONCLUSION: A continuous infusion of phentolamine was used in a
      patient with pheochromocytoma to control perioperative hypertensive episodes
      during surgical adrenalectomy.

PMID- 21200060
TI  - Systemic absorption of topical lidocaine in a bone marrow transplant recipient
      with hepatic sinusoidal obstruction syndrome.
AB  - PURPOSE: A case of systemic lidocaine exposure in a bone marrow transplant
      recipient with severe hepatic sinusoidal obstruction syndrome (SOS) receiving
      treatment with lidocaine patch 5% is reported. SUMMARY: A 35-year-old Caucasian
      man with a history of refractory acute lymphoblastic leukemia was admitted for a
      third allogeneic, mismatched, peripheral blood hematopoietic stem cell transplant
      from an unrelated donor, with a conditioning regimen that included busulfan and
      fludarabine. The patient was receiving treatment with lidocaine patch 5% (two
      patches daily, which was started five months before another hospital admission
      for the treatment of vincristine-related peripheral neuropathy. Baseline
      laboratory findings were within normal limits except for disease-related
      neutropenia and thrombocytopenia. Twenty days after hematopoietic stem cell
      transplantation (HSCT), the patient developed signs and symptoms of severe
      hepatic SOS. His serum alanine transaminase concentration rose from 65 IU/L at
      baseline to 370 IU/L, and his serum aspartate transaminase concentration rose
      from 32 IU/L at baseline to 871 IU/L. His total bilirubin increased to 2.8 mg/dL,
      and his body weight increased by 15%. An abdominal ultrasound noted ascites and
      hepatomegaly without reversal of blood flow. The lidocaine patch was
      discontinued, but the patient's condition continued to deteriorate. He died 38
      days after HSCT from complications of severe hepatic SOS. CONCLUSION: A 35-year
      old man developed hepatic SOS 20 days after his third HSCT. As a result of his
      hepatic impairment, the patient, who had been receiving lidocaine patch 5% for
      the treatment of neuropathic pain, experienced increased systemic exposure to
      lidocaine, which led to discontinuation of the patch.

PMID- 21200061
TI  - Managing the atazanavir-tacrolimus drug interaction in a renal transplant
      recipient.
AB  - PURPOSE: The management of the drug interaction between atazanavir and tacrolimus
      in a renal transplant recipient is described. SUMMARY: A 53-year-old African
      American man with human immunodeficiency virus (HIV) received a renal transplant
      and was treated in accordance with a corticosteroid-sparing immunosuppressive
      protocol and maintenance immunosuppression with mycophenolate mofetil and
      tacrolimus. His highly active antiretroviral therapy included atazanavir 400 mg
      daily, abacavir 600 mg daily, and lamivudine 100 mg daily. Because of the
      potential for a significant interaction between tacrolimus and atazanavir, the
      tacrolimus dosage was to be based on serum tacrolimus concentrations. The patient
      was initially administered one dose of tacrolimus 0.5 mg on the morning of
      postoperative day 2. Evaluation of the tacrolimus profiles revealed that a higher
      dosage was necessary because serum tacrolimus levels decreased to subtherapeutic
      levels by 6 hours after dose administration. In an attempt to minimize tacrolimus
      toxicity and limit the duration of a subtherapeutic tacrolimus level, dosing was
      adjusted to 1 mg every 8 hours. After 48 hours of this regimen, peak serum
      tacrolimus levels were lower, and the drug concentrations remained at a
      relatively steady level throughout the dosing interval. One final dosage
      adjustment (1.5 mg every 12 hours) was performed to optimize serum tacrolimus
      levels and patient compliance. CONCLUSION: In a 53-year-old man with HIV
      infection who underwent renal transplantation, the drug interaction between
      atazanavir and tacrolimus was managed by modifying the tacrolimus dosage regimen
      after determining the patient's blood tacrolimus concentration profile.

PMID- 21200064
TI  - Addition of electronic prescription transmission to computerized prescriber order
      entry: Effect on dispensing errors in community pharmacies.
AB  - PURPOSE: The addition of electronic prescription transmission to computerized
      prescriber order entry (CPOE) and its effect on dispensing errors in community
      pharmacies were evaluated. METHODS: A controlled, before-and-after trial to
      measure the effect of electronic prescribing on dispensing errors in two control
      clinics and one e-prescribing clinic already using CPOE was conducted between
      January and November 2006. Prescriptions documented within the CPOE system were
      reconciled with dispensed prescription information from participating pharmacy
      chains via a national pharmacy information exchange network. Dispensing errors
      were defined as discrepancies between the prescriber's written orders and the
      dispensed prescription information. Prescriptions filled at nonparticipating
      pharmacies were not analyzed. RESULTS: A total of 11,447 prescriptions were
      written in the control clinics, and 29,575 were written in the e-prescribing
      clinic. During the intervention period, 2,179 (22%) of 9,905 intervention clinic
      prescriptions were electronically transmitted, including 621 (28%) available for
      analysis. There was no significant difference in the dispensing-error rates
      between the baseline and intervention periods for the control clinics. Similarly,
      the dispensing-error rates did not differ significantly for the e-prescribing
      clinic between the baseline and intervention periods for prescriptions that were
      not electronically transmitted. The e-prescribing clinic's dispensing-error rate
      for electronically transmitted prescriptions during the intervention was
      significantly lower than its baseline dispensing-error rate (p = 0.03).
      CONCLUSION: Electronic transmission of prescription data from physicians' offices
      to a pharmacy nearly halved the risk of dispensing errors compared with
      generating the prescription with outpatient CPOE and printing it and giving it to
      the patient.

PMID- 21200062
TI  - Development and implementation of a pharmacist-managed clinical pharmacogenetics
      service.
AB  - PURPOSE: The development and implementation of a pharmacist-managed clinical
      pharmacogenetics service are described. SUMMARY: A pharmacist-managed clinical
      pharmacogenetics service was designed and implemented at an academic specialty
      hospital to provide clinical pharmacogenetic testing for gene products important
      to the pharmacodynamics of medications used in the hospital's patients. A series
      of accredited educational seminars were conducted for our pharmacists to
      establish competencies in providing pharmacogenetic consults for the genes to be
      tested by the clinical pharmacogenetics service. The service was modeled after
      and integrated with an already-established clinical pharmacokinetics service. A
      steering committee was formed to evaluate the use of available tests, new
      evidence for implementation of additional tests, and other service quality
      metrics. All clinical pharmacogenetic test results are first reported to one of
      the pharmacists, who reviews the result and provides a written consultation. The
      consultation includes an interpretation of the result and recommendations for any
      indicated changes to therapy. In 2009, 136 clinical pharmacogenetic tests were
      performed. The service has been met with positive clinician feedback. The
      successful implementation of this service highlights the leadership role that
      pharmacists can take in moving pharmacogenetics from research to patient care.
      CONCLUSION: The development of and experience with a pharmacist-managed clinical
      pharmacogenetics service are described. The program's success has depended on
      collaboration between the clinical laboratory and pharmacists, and pharmacists'
      pharmacogenetic recommendations have been well accepted by prescribers.

PMID- 21200063
TI  - Evaluation of a modified prescription form to address prescribing errors.
AB  - PURPOSE: The impact of a modified paper prescription form on the occurrence of
      prescribing errors was evaluated. METHODS: Rural primary care providers
      practicing in the United States who wrote paper prescriptions in English were
      eligible for study participation. The prescribers agreed to use only the
      prescription pads provided to them during the study. The study prescription pads
      contained 50 prescription forms, each with a duplicate. Each prescription and
      duplicate contained a unique serial number for data identification purposes. When
      a prescriber wrote a prescription, the original was provided to the patient per
      usual practice, and the duplicate was retained as the study data. Two
      prescription pads contained modified forms and two prescription pads were similar
      to the prescription pads the prescriber had been using. Providers completed 100
      standard and 100 modified prescriptions. Pharmacist consultants reviewed each
      prescription for the presence or absence of errors. The primary outcome measure
      was the number of errors. Secondary outcomes were risk differences between
      standard and modified prescription forms for various error types. RESULTS: Of the
      327 prescribers who were eligible and expressed interest in the study, 111
      started the study and 84 completed the study. A total of 16,061 prescriptions
      were eligible for analysis. Pharmacists identified at least one prescribing
      problem in 987 prescriptions (6.1%). Modified prescription forms were associated
      with significantly more prescribing problems than standard prescription forms
      (odds ratio, 1.85; 95% confidence interval, 1.5-2.2; p < 0.001). CONCLUSION:
      Modified prescription forms were associated with more errors than were standard
      prescription forms in a sample of rural prescribers.

PMID- 21200065
TI  - Functions performed by paid pharmacy interns in hospitals in New York.
AB  - PURPOSE: The types of clinical and nonclinical activities performed by paid
      pharmacy interns in the hospitals in New York state were studied. METHODS: In
      November 2008, a list of hospitals in New York was obtained from the website of
      the New York State Department of Health. A survey was sent to each hospital's
      pharmacy director requesting information on hospital characteristics and whether
      the pharmacy department employed nongraduate pharmacy interns. For those
      hospitals that employed pharmacy interns, questions were asked about the number
      of nongraduate pharmacy interns employed, the shifts worked by interns, whether
      there was a minimum work-hour requirement for interns, the functions routinely
      performed by interns, and the percentage of interns who remained employed at the
      hospital upon licensure. RESULTS: Of the 184 surveys distributed, 96 responses
      (52.2%) were received. The majority of hospitals had 400 beds or fewer and were
      teaching institutions, and 45 employed pharmacy interns. The five functions
      reported most frequently were answering telephone calls (91%), preparing and
      distributing medications (82%), compounding nonparenteral medications (69%),
      compounding parenteral medications (62%), and responding to drug information
      queries (51%). The mean +/- S.D. number of clinical activities performed by
      interns was 2.1 +/- 2.1. The most frequently reported clinical activities were
      responding to drug information queries (51.1%), performing clinical interventions
      (33.3%), and completing adverse-drug-reaction reports (31.1%). CONCLUSION:
      Hospital pharmacy departments in New York utilized paid pharmacy interns to
      perform a variety of functions, including clinical activities. While there
      appears to be recognition that interns can perform clinical activities, the mean
      number of such activities was relatively low.

PMID- 21200066
TI  - Evaluating an approach to improving the adoption rate of wireless drug library
      updates for smart pumps.
AB  - PURPOSE: An academic medical center's approach to improving the adoption rate of
      wireless drug library updates for smart pumps was evaluated. SUMMARY: A
      multidisciplinary team composed of pharmacy, nursing, medical engineering,
      materials management, and patient equipment personnel at an academic medical
      center collaborated to update the drug libraries of more than 1800 smart pumps
      via a wireless control system. Two pilot tests were completed to identify and
      resolve issues before the live wireless update was attempted. The second pilot
      test, a passive approach, produced an adoption rate of 42% of 1804 pumps at the
      end of one week and a rate of 56% on day 10. The goal of 80% was not achieved
      until day 22. The change to an active multidisciplinary process three months
      later produced an adoption rate of 80% for 1869 pumps on day 10, resulting in a
      45.4% increase in the adoption rate between the two trials on day 10 (p < 0.001).
      Communication regarding the updates was disseminated via e-mail to the entire
      organization, with fliers posted on all patient care units, and verbally during
      staff meetings. Patient equipment personnel manually tagged each pump with a blue
      zip tie after verifying the update to easily identify which pumps had been
      updated. Areas for improvement include increasing communication to the staff
      detailing when the update will occur and changing the day of the week the update
      is performed. CONCLUSION: A multidisciplinary team actively engaged in the
      updating of wireless i.v. smart pump drug libraries reduced the amount of time
      required to reach a goal adoption rate of 80%.

PMID- 21200067
TI  - Erving Goffman's Asylums 50 years on.
AB  - Erving Goffman's Asylums: Essays on the Social Situation of Mental Patients and
      Other Inmates is a key text in the sociology of mental illness. It is sometimes
      seen simplistically as a paradigm of'antipsychiatry', and as a key step in the
      triumph of community psychiatry over narrower, medical models of mental illness.
      Reading Asylums today, however, reveals that this portrayal does not capture the
      richness of the text. My argument is that, rather than being an opponent of
      biological psychiatry or medical models per se, Goffman's key role was in
      humanising patients and drawing attention to the patterns of interaction that
      dehumanised them.

PMID- 21200068
TI  - Ways of working at the interface between primary and specialist mental
      healthcare.
AB  - Ways of working at the interface between primary and specialist care are
      considered with discussion of the limits of available evidence and the potential
      for a new role for psychiatrists in providing supervision and consultation in
      novel models of care.

PMID- 21200069
TI  - The smoking culture in psychiatry: time for change.
AB  - Smoking is closely linked to severe mental illness and has a major detrimental
      impact on individuals' lives. Despite this and the recent societal 'de
      normalisation' of smoking, the historic 'smoking culture' still prevails within
      mental health settings. Change is urgently required to prevent a widening of
      existing health gaps.

PMID- 21200070
TI  - Eating disorders, DSM-5 and clinical reality.
AB  - The DSM-IV scheme for classifying eating disorders is a poor reflection of
      clinical reality. In adults it recognises two conditions, anorexia nervosa and
      bulimia nervosa, yet these states are merely two presentations among many. As a
      consequence, at least half the cases seen in clinical practice are relegated to
      the residual diagnosis 'eating disorder not otherwise specified'. The changes
      proposed for DSM-5 will only partially succeed in correcting this shortcoming.
      With DSM-6 in mind, it is clear that comprehensive transdiagnostic samples need
      to be studied with data collected on their current state, course and response to
      treatment. Only with such data will it be possible to derive an empirically based
      classificatory scheme that is both rooted in clinical reality and of value to
      clinicians.

PMID- 21200071
TI  - Efficacy of antidepressants and benzodiazepines in minor depression: systematic
      review and meta-analysis.
AB  - BACKGROUND: Depression is a common condition that has been frequently treated
      with psychotropics. AIMS: To review systematically the evidence of efficacy and
      acceptability of antidepressant and benzodiazepine treatments for patients with
      minor depression. METHOD: A systematic review and meta-analysis of double-blind
      randomised controlled trials comparing antidepressants or benzodiazepines v.
      placebo in adults with minor depression. Data were obtained from MEDLINE, CINAHL,
      EMBASE, PsycInfo, Cochrane Controlled Trials Register and pharmaceutical company
      websites. Risk of bias was assessed for the generation of the allocation
      sequence, allocation concealment, masking, incomplete outcome data, and
      sponsorship bias. RESULTS: Six studies met inclusion criteria. Three studies
      compared paroxetine with placebo; fluoxetine, amitriptyline and isocarboxazid
      were studied in one study each. No studies compared benzodiazepines with placebo.
      In terms of failures to respond to treatment (6 studies, 234 patients treated
      with antidepressants and 234 with placebo) no significant difference between
      antidepressants and placebo was found (relative risk (RR) 0.94, 95% CI 0.81
      1.08). In terms of acceptability, data extracted from two studies (93 patients
      treated with antidepressants and 93 with placebo) showed no statistically
      significant difference between antidepressants and placebo (RR=1.06, 95% CI 0.65
      1.73). There was no statistically significant between-study heterogeneity for any
      of the reported analyses. CONCLUSIONS: There is evidence showing there is
      unlikely to be a clinically important advantage for antidepressants over placebo
      in individuals with minor depression. For benzodiazepines, no evidence is
      available, and thus it is not possible to determine their potential therapeutic
      role in this condition.

PMID- 21200073
TI  - Relationship duration and mental health outcomes: findings from a 30-year
      longitudinal study.
AB  - BACKGROUND: Marriage is known to be associated with improved mental health, but
      little research has examined whether the duration of a cohabiting relationship is
      associated with mental health. AIMS: To examine the associations between
      relationship duration and mental health problems in a birth cohort of 30-year
      olds. METHOD: Associations between relationship duration and mental health were
      examined using a generalised estimating equation approach. Associations were
      adjusted for covariates, including prior mental health problems. RESULTS: Longer
      relationship duration was significantly associated with lower rates of
      depression, suicidal behaviour and substance abuse/dependence, even after
      adjustment for covariates. In most cases the associations did not vary with
      gender. Legal relationship status (legally or de facto married) was not
      significantly related to mental health once due allowance was made for
      relationship duration. CONCLUSIONS: Increasing relationship duration, but not
      legal relationship status, has a protective effect on mental health for men and
      women.

PMID- 21200072
TI  - Timing of menarche and depressive symptoms in adolescent girls from a UK cohort.
AB  - BACKGROUND: A growing number of studies suggest a link between timing of menarche
      and risk of depressive symptoms in adolescence, but few have prospectively
      examined the emergence of depressive symptoms from late childhood into
      adolescence. AIMS: To examine whether girls who experience earlier menarche than
      their peers have higher levels of depressive symptoms in adolescence. METHOD: The
      study sample comprised 2184 girls from the Avon Longitudinal Study of Parents and
      Children. The association between timing of menarche and depressive symptoms at
      10.5, 13 and 14 years was examined within a structural equation model. RESULTS:
      Girls with early menarche (<11.5 years) had the highest level of depressive
      symptoms at 13 (P=0.007) and 14 years (P<0.001) compared with those with
      normative and late timing of menarche. CONCLUSIONS: Early maturing girls are at
      increased risk of depressive symptoms in adolescence and could be targeted by
      programmes aimed at early intervention and prevention.

PMID- 21200074
TI  - Mortality and suicide after self-harm: community cohort study in Taiwan.
AB  - BACKGROUND: Little is known about outcomes after self-harm in East Asia. AIMS: To
      investigate mortality after self-harm in a Taiwanese population. METHOD: Between
      2000 and 2003, 1083 individuals who self-harmed were identified through a
      population self-harm register in Nantou County, Taiwan, and followed until 2007
      for date and cause of death on a national mortality database. RESULTS: In total,
      145 individuals died, 48 through suicide. The risks of all-cause and suicide
      mortality in the first year were 4.7% and 2.1% respectively, representing 8- and
      131-fold age- and gender-standardised increases. Male gender and older age were
      independent risk factors for both suicide and non-suicide mortality. Use of more
      lethal methods in the index episode was associated with higher mortality but this
      was accounted for by gender. CONCLUSIONS: Results in this sample support the
      recommendation that people with a history of recent self-harm should be a major
      target for suicide prevention programmes.

PMID- 21200075
TI  - Prospective cohort study of mental health during imprisonment.
AB  - BACKGROUND: Mental illness is common among prisoners, but little evidence exists
      regarding changes in symptoms in custody over time. AIMS: To investigate the
      prevalence and predictors of psychiatric symptoms among prisoners during early
      custody. METHOD: In a prospective cohort study, 3079 prisoners were screened for
      mental illness within 3 days of reception. To establish baseline diagnoses and
      symptoms, 980 prisoners were interviewed; all remaining in custody were followed
      up 1 month and 2 months later. RESULTS: Symptom prevalence was highest during the
      first week of custody. Prevalence showed a linear decline among men and convicted
      prisoners, but not women or remand prisoners. It decreased among prisoners with
      depression, but not among prisoners with other mental illnesses. CONCLUSIONS:
      Overall, imprisonment did not exacerbate psychiatric symptoms, although
      differences in group responses were observed. Continued discussion regarding non
      custodial alternatives for vulnerable groups and increased support for all during
      early custody are recommended.

PMID- 21200076
TI  - Social network media exposure and adolescent eating pathology in Fiji.
AB  - BACKGROUND: Mass media exposure has been associated with an increased risk of
      eating pathology. It is unknown whether indirect media exposure--such as the
      proliferation of media exposure in an individual's social network--is also
      associated with eating disorders. AIMS: To test hypotheses that both individual
      (direct) and social network (indirect) mass media exposures were associated with
      eating pathology in Fiji. METHOD: We assessed several kinds of mass media
      exposure, media influence, cultural orientation and eating pathology by self
      report among adolescent female ethnic Fijians (n=523). We fitted a series of
      multiple regression models of eating pathology, assessed by the Eating Disorder
      Examination Questionnaire (EDE-Q), in which mass media exposures,
      sociodemographic characteristics and body mass index were entered as predictors.
      RESULTS: Both direct and indirect mass media exposures were associated with
      eating pathology in unadjusted analyses, whereas in adjusted analyses only social
      network media exposure was associated with eating pathology. This result was
      similar when eating pathology was operationalised as either a continuous or a
      categorical dependent variable (e.g. odds ratio OR=1.60, 95% CI 1.15-2.23
      relating social network media exposure to upper-quartile EDE-Q scores).
      Subsequent analyses pointed to individual media influence as an important
      explanatory variable in this association. CONCLUSIONS: Social network media
      exposure was associated with eating pathology in this Fijian study sample,
      independent of direct media exposure and other cultural exposures. Findings
      warrant further investigation of its health impact in other populations.

PMID- 21200077
TI  - Rapid acute treatment of agitation in individuals with schizophrenia:
      multicentre, randomised, placebo-controlled study of inhaled loxapine.
AB  - BACKGROUND: There is a need for a rapid-acting, non-injection, acute treatment
      for agitation. AIMS: To evaluate inhaled loxapine for acute treatment of
      agitation in schizophrenia. METHOD: This phase III, randomised, double-blind,
      placebo-controlled, parallel-group study (ClinicalTrials.gov number NCT00628589)
      enrolled 344 individuals who received one, two or three doses of inhaled loxapine
      (5 or 10 mg) or a placebo. Lorazepam rescue was permitted after dose two. The
      primary efficacy end-point was change from baseline in Positive and Negative
      Syndrome Scale-Excited Component (PANSS-EC) 2 h after dose one. The key secondary
      end-point was Clinical Global Impression-Improvement scale (CGI-I) score 2 h
      after dose one. RESULTS: Inhaled loxapine (5 and 10 mg) significantly reduced
      agitation compared with placebo as assessed by primary and key secondary end
      points. Reduced PANSS-EC score was evident 10 min after dose one with both 5 and
      10 mg doses. Inhaled loxapine was well tolerated, and the most common adverse
      events were known effects of loxapine or minor oral effects common with inhaled
      medications. CONCLUSIONS: Inhaled loxapine provided a rapid, well-tolerated acute
      treatment for agitation in people with schizophrenia.

PMID- 21200078
TI  - Cognitive-behavioural therapy for persistent and recurrent psychosis in people
      with schizophrenia-spectrum disorder: cost-effectiveness analysis.
AB  - BACKGROUND: Evidence on cost-effectiveness is important to make well-informed
      decisions regarding care delivery. AIMS: To determine the balance between costs
      and health outcomes of cognitive-behavioural therapy (CBT) compared with
      treatment as usual (TAU) in people with schizophrenia who have persistent and
      recurrent symptoms of psychosis. TRIAL NUMBER: ISRCTN57292778. METHOD: A total of
      216 people were randomised and followed up for 18 months. The primary clinical
      outcome measure was time functioning within the normal range. Normal functioning
      was defined as social functioning within the 95% range of the general population
      and no or minimal suffering and/or no or minimal affect on daily life of
      persistent psychotic symptoms. The difference in number of days was estimated.
      Using a societal perspective, cost differences were estimated and combined with
      clinical outcome to yield an incremental cost-effectiveness ratio (ICER).
      Uncertainty was accessed using bootstrapping and displayed by means of a cost
      effectiveness acceptability curve. RESULTS: In the CBT group, participants
      experienced 183 days of normal social functioning, whereas the TAU group
      experienced 106 days. The ICER was ?47 per day of normal functioning gained.
      Cognitive-behavioural therapy implies higher costs, yet results in better health
      outcomes. Sensitivity analyses showed that targeting individuals who have not
      been hospitalised before receiving CBT results in an ICER of ?14 per day normal
      functioning gained. CONCLUSIONS: Days of normal functioning improved in the CBT
      condition compared with TAU, but this gain in health was associated with
      additional societal costs.

PMID- 21200079
TI  - Behavioural activation delivered by the non-specialist: phase II randomised
      controlled trial.
AB  - BACKGROUND: Behavioural activation appears as effective as cognitive-behaviour
      therapy (CBT) in the treatment of depression. If equally effective, then
      behavioural activation may be the preferred treatment option because it may be
      suitable for delivery by therapists with less training. This is the first
      randomised controlled trial to look at this possibility. AIMS: To examine whether
      generic mental health workers can deliver effective behavioural activation as a
      step-three high-intensity intervention. METHOD: A randomised controlled trial
      (ISRCTN27045243) comparing behavioural activation (n=24) with treatment as usual
      (n=23) in primary care. RESULTS: Intention-to-treat analyses indicated a
      difference in favour of behavioural activation of -15.79 (95% CI -24.55 to -7.02)
      on the Beck Depression Inventory-II and Work and Social Adjustment Scale (mean
      difference -11.12, 95% CI -17.53 to -4.70). CONCLUSIONS: Effective behavioural
      activation appears suitable for delivery by generic mental health professionals
      without previous experience as therapists. Large-scale trial comparisons with an
      active comparator (CBT) are needed.

PMID- 21200080
TI  - Depression and smoking.

PMID- 21200081
TI  - Evolution and non-clinical psychotic symptoms.

PMID- 21200082
TI  - Evolution and non-clinical psychotic symptoms.

PMID- 21200083
TI  - Evolution and non-clinical psychotic symptoms.

PMID- 21200084
TI  - From binary to multivalued to continuous models: the lac operon as a case study.
AB  - Using the lac operon as a paradigmatic example for a gene regulatory system in
      prokaryotes, we demonstrate how qualitative knowledge can be initially captured
      using simple discrete (Boolean) models and then stepwise refined to multivalued
      logical models and finally to continuous (ODE) models. At all stages, signal
      transduction and transcriptional regulation is integrated in the model
      description. We first show the potential benefit of a discrete binary approach
      and discuss then problems and limitations due to indeterminacy arising in cyclic
      networks. These limitations can be partially circumvented by using multilevel
      logic as generalization of the Boolean framework enabling one to formulate a more
      realistic model of the lac operon. Ultimately a dynamic description is needed to
      fully appreciate the potential dynamic behavior that can be induced by regulatory
      feedback loops. As a very promising method we show how the use of multivariate
      polynomial interpolation allows transformation of the logical network into a
      system of ordinary differential equations (ODEs), which then enables the analysis
      of key features of the dynamic behavior.

PMID- 21200085
TI  - Brain natriuretic peptide rs198388 polymorphism and essential hypertension in
      Hunan Han people.
AB  - OBJECTIVE: To investigate the relation between brain natriuretic peptide (BNP)
      rs198388 polymorphism and the susceptibility of essential hypertension in Han
      population of Hunan. METHODS: A total of 567 patients with hypertension (the
      hypertension group) and 555 healthy volunteers (the control group) were enrolled.
      Gender, age, smoking and drinking history of the 2 groups were not significantly
      different. Blood pressure was measured in the 2 groups. After fasting for 12 h or
      more, blood glucose, total cholesterol, triglycerides, high density lipoprotein
      cholesterol and low density lipoprotein cholesterol were measured. DNA
      polymorphism analysis was done by polymerase chain reaction-restriction fragment
      length polymorphism method, and genotype was determined by agarose gel
      electrophoresis. RESULTS: The GG, GA, and AA genotypes were detected.The
      frequencies of GA and AA genotypes and A allele were significantly lower in the
      hypertension group (GA and AA:12.3%;A:6.9%) than those in the control group (GA
      and AA:18.4%; A:9.7%; P=0.009, and P=0.014, respectively). CONCLUSION: BNP
      rs198388 polymorphism may be associated with essential hypertension in Han people
      in Hunan. Carrying rs198388 GA and AA genotypes and A allele may be the reason
      for low risk of hypertension.

PMID- 21200086
TI  - Metabonomic analysis of rat urine 1H magnetic resonance spectra based on
      different normalization methods.
AB  - OBJECTIVE: To study metabonomics in the urine of rats of different genders by
      magnetic resonance (MR) with 2 normalization methods. METHODS: Different
      normalization methods such as mean-centering not scaling (Ctr) and unit variance
      scaling (UV) were used before orthogonal to partial least squares discriminant
      analysis(OPLS-DA). Distinguished metabolites in the urine of different gender
      rats were analyzed by calculating the correlation coefficients. RESULTS: The data
      normalized by Ctr before OPLS-DA analysis revealed high degree conception
      metabolites in the urine such as valine, alanine, acetate, ornithine,
      aminohippurate, phenylethylamine, cytosine, citrate, dimethylamine, allantoin,
      methylamine, fumarate and one unknown metabolite whose chemical shift was
      delta4.14. Data normalized by UV before OPLS-DA analysis revealed the above 12
      high degree conception metabolites except citrate, and also low degree conception
      metabolites such as thiamine, creatinine, formate and one unknown metabolite
      whose chemical shift was delta2.92. CONCLUSION: Unit variance scaling is a more
      effective normalization method in metabonomic analysis.

PMID- 21200087
TI  - Expression of MGMT and its clinopathological significance in thyroid carcinoma.
AB  - OBJECTIVE: To study the expression of O(6)-methylguanine-DNA methyltransferase
      (MGMT) and its clinicopathological significance in thyroid cancer. METHODS:
      Immunohistochemistry was used to determine the expression of MGMT in 61 thyroid
      cancer tissues, 21 thyroid adenomas, 15 Hashimoto's thyroiditis, 8 nodular
      goiter, and 12 peri-tumor tissues. RESULTS: There was statistic difference in the
      expression of MGMT between the normal tissues and thyroid cancers (P<0.05).
      Expression of MGMT increased from the normal tissue (16.67%, 10/12), nodular
      goiter (25.00%, 2/8), Hashimoto's thyroiditis (60.00%, 9/15), and thyroid adenoma
      (52.38%, 11/21)to thyroid cancer (60.66%, 38/61). Expression of MGMT in papillary
      thyroid cancer (PTC) and follicular thyroid cancer (FTC) had significant
      difference (P<0.05), and the expression level of MGMT decreased with the
      malignancy of thyroid cancer, such as in PTC (72.22%, 26/36), and FTC (50.00%,
      8/16). There was no statistic difference in MGMT expression in sex, age, and
      nationality (P>0.05). CONCLUSION: High expression of MGMT might be related to the
      malignancy of thyroid cancer, which may be one of the diagnosis indexes for
      thyroid cancer. It will be a common clinical index in diagnosing thyroid cancer
      since there is no difference in MGMT expression among sexes, ages, and
      nationalities.

PMID- 21200088
TI  - [Association between polymorphism of rs3212855 and rs5515 of KLK1 gene with
      cerebral hemorrhage in Changsha Han population].
AB  - OBJECTIVE: To explore the association between single nucleotide polymorphism
      (SNPs) of KLK1 gene and cerebral hemorrhage in Changsha Han population. METHODS:
      We enrolled 273 patients with cerebral hemorrhage and 140 normal people. The SNPs
      (including rs3212855 and rs5515) of KLK1 gene were analyzed by Snapshot method
      and direct sequencing. RESULTS: We found rs5515 was not a polymorphic site in
      Changsha Han population. Genotype and allele frequency in rs3212855 were not
      different between patients with cerebral hemorrhage and the controls (P>0.05).
      The blood pressure level was not different between the genotype subgroups.
      CONCLUSION: Neither rs5515 nor rs3212855 is associated with cerebral hemorrhage.

PMID- 21200089
TI  - [SARA expression in high glucose induced epithelium to mesenchymal transition of
      proximal tubule cells].
AB  - OBJECTIVE: To construct the cell model of epithelium to mesenchymal transition of
      proximal tubule cells induced by high glucose and to determine the expression of
      Smad anchor for receptor activation (SARA). METHODS: Protein expression of
      vimentin, Zona occludens-1(ZO-1), and SARA was determined by Western blot, and
      their mRNA expressions were detected by Real-time PCR. RESULTS: After stimulation
      by 30 mmol/L D-glucose, the protein and mRNA expression levels of vimentin in HK
      2 cells increased in a time-dependent manner while the expression of ZO-1 was
      reduced significantly, especially at 48 h. Meanwhile, SARA was also decreased in
      a time-dependent manner. CONCLUSION: High glucose can induce renal epithelium to
      mesenchymal transition, and SARA may be involved in this process as a protector.

PMID- 21200090
TI  - [LUNX mRNA in regional lymph nodes of non-small cell lung cancer patients by RT
      PCR and its clinical significance].
AB  - OBJECTIVE: To evaluate the detection of humen-lung-specific X protein (LUNX) gene
      in micrometastases of patients with non-small cell lung cancer. METHODS: The
      expression of LUNX gene in tumor tissue, lung and lymph nodes was detected by
      reverse transcriptase-polymerase chain reaction(RT-PCR) both in 43 non-small-cell
      lung cancer patients (the experimental group) and 15 lung benign patients (the
      control group). LUNX mRNA expression in clinic pathology,stage of cancer cell
      differentiation, clinic stage, age, sex, smoking history, and 4 lung cancer blood
      markers (CEA,CA125,NSE, and CYFRA211) were evaluated. RESULTS: The expression of
      LUNX gene was positive in the 2 groups. LUNX gene expression was positive in 33
      of the 87 lymph nodes of the 43 patients in the experimental group (37.93%), and
      in 2 of the 26 lymph nodes in the control group (7.69%). The LUNX mRNA positive
      in the lymph nodes was closely related to the pathological type, cancer cell
      differentiation and clinic stage(r=0.660,0.500,0.460; P=0.011,0.017,0.022, all
      P<0.05), while not closely related to age, sex, smoking history and 4 lung cancer
      blood markers (CEA,CA125, NSE, and CYFRA211) (r=0.111, 0.135,0.083,0.354;
      P=0.739,0.714,0.773,0.125,all P>0.05). CONCLUSION: The LUNX mRNA expression
      detected by RT-PCR is more sensitive than by traditional ways. The expression of
      LUNX gene mRNA in the lymph nodes is a valuable index for the detection of
      micrometastases in patients with non-small cell lung cancer.

PMID- 21200091
TI  - [Correlation between multi-slice spiral CT pulmonary perfusion imaging and cavity
      of microvessel in lung cancer].
AB  - OBJECTIVE: To investigate the relation between multi-slice spiral CT pulmonary
      perfusion imaging and the cavity of microvessel in lung cancer. METHODS:
      Altogether 36 patients with malignant nodules who underwent multi-slice spiral CT
      perfusion scan were examined.The perfusion parameters were collected and compared
      with the microvessel density (MVD), the incomplete lumen MVD, and the
      differentiation of non-small cell lung cancer (NSCLC). The patients were divided
      into a hyper-perfusion group and a hypo-perfusion group by the value of perfusion
      parameters. The maturity of microvessel and the degree of differentiation in
      NSCLC between the 2 groups was analyzed. RESULTS: Blood flow (BF), blood volume
      (BV), and peak enhancement image(PEI) of the malignant nodules were (39.7+/-11.5)
      mL/(100 mg.min), (8.6+/-3.8)mL/100 g, and (20.1+/-8.6)HU, respectively. There was
      a positive correlation between PEI and MVD(r=0.645,P<0.01), and a negative
      correlation between BF and MVD(r=-0.280,P=0.048). There were negative
      correlations of BF, BV, PEI with the incomplete lumen MVD (P<0.05). BF had the
      highest correlation coefficient(r=-0.882,P<0.01).The incomplete lumen MVD of the
      hyper-perfusion group was significantly lower than that of hypo-perfusion group
      (P<0.05),but there was no significant difference in MVD between the 2 groups.
      There were negative correlations of BF, BV,PEI with the degree of differentiation
      (P<0.05). BF had the highest correlation coefficient(r=-0.751,P<0.01).
      CONCLUSION: Multi-slice spiral CT pulmonary perfusion imaging is helpful to
      evaluate the degree of differentiation and status of angiogenesis in lung cancer,
      and its basis is the cavity of microvessel.

PMID- 21200092
TI  - [Effect of nylestriol and levonorgestrel on the expression of estrogen receptor
      subtypes in human osteosarcoma MG-63 cell lines].
AB  - OBJECTIVE: To observe the effect of different concentrations of nylestriol (NYL)
      and levonorgestrel (LNG) on the expression of ERalpha and ERbeta in human
      osteoscarcoma MG-63 cell lines, and to explore the impact of paracrine effect on
      the gene expression. METHODS: MG-63 cells were treated with 3 concentrations (10(
      10),10(-8), and 10(-6) mol/L) of NYL or LNG. The untreated control group and the
      positive control group were also established. The 2 groups treated with NYL (10(
      10) mol/L) or LNG (10(-8) mol/L) were designed to renew the medium every 12 h.
      Semi-quantitative RT-PCR was conducted to detect the mRNA expression of ERalpha
      and ERbeta on the MG-63 cells treated with different concentrations of the 2
      drugs, respectively. RESULTS: Both drugs up-regulated ERalpha and ERbeta mRNA
      expression. The best concentration for both NYL and LNG was 10(-6) mol/L for
      ERalpha expression. As for ERbeta, the best concentration of NYL and LNG was 10(
      10) mol/L and 10(-8) mol/L. The role of medium replacement on the expression of
      ERalpha was not observed, but medium replacement inhibited ERbeta expression.
      CONCLUSION: Both NYL and LNG can up-regulate the mRNA expression of ER subtypes
      in MG-63 cells, with mutual restriction between the 2 subtypes. The paracrine
      effect on MG-63 cell lines may be involved in the regulation process of mRNA
      expression of ERbeta.

PMID- 21200093
TI  - [Effect of glucagon like peptide-1 on proliferation and differentiation of
      endothelial progenitor cells and its mechanism].
AB  - OBJECTIVE: To investigate the effect and mechanism of glucagon like peptide 1(GLP
      1)on the proliferation and differentiation of endothelial progenitor
      cells(EPCs)derived from the peripheral blood. METHODS: Mononuclear cells were
      isolated from human peripheral blood by density gradient centrifugation. After 7
      days of culture,attached cells were stimulated with different cultures of 0.2%
      BSA,and GLP-1(1,10,and 20 nmol/L). Laser scanning confocal microscope was used to
      determine the EPCs from human peripheral blood.The activity of EPCs was observed
      under reverse microscope. MTT was used to determine the proliferation of EPCs.
      The expression of KDR,Flt-1,VE-cadherin,and eNOS mRNA was detected by RT-PCR.The
      concentration of serum VEGF was detected by ELISA. The expression of VEGF protein
      was detected by immunohistochemical SP method. The EPCs cultured in GLP-1 were
      intervened by VEGFmAb. RESULTS: EPCs was proliferated more in the GLP-1
      group(1,10,and 20 nmol/L) than in the control group (P<0.05 or P<0.01). The
      expression of KDR,FLT-1,VE-cadherin,eNOS mRNA and VEGF protein was higher than
      that in the control group(P<0.05 or P<0.01). VEGFmAb(100 ng/mL)down-regulated the
      expression of KDR,Flt-1,VE-cadherin,and eNOS mRNA. CONCLUSION: GLP-1 can promote
      the proliferation and differentiation of EPCs derived from the peripheral blood
      by up-regulating VEGF autocrine.

PMID- 21200094
TI  - [Effect of pregnancy-associated plasma protein-A on the function of endothelial
      cells].
AB  - OBJECTIVE: To determine the effect of pregnancy-associated plasma protein A (PAPP
      A) on the function of vascular endothelial cells (VEC). METHODS: Human umbilical
      vein endothelial cell (HUVEC) line, derived from human umbilical vein, was
      cultured in vitro with PAPP-A at 0, 50, 100, and 200 ng/mL for 0, 12, 24, and 48
      hours, respectively. Nitric oxide (NO) levels and endothlin-1 (ET-1) levels were
      determined by spectrophotometer and immunehistory. RESULTS: The NO levels of
      HUVECs in the PAPP-A groups were significantly lower than those in the control
      group (P<0.05). The ET-1 levels of HUVECs in the PAPP-A groups were significantly
      higher than those in the control group (P<0.05). The changes were all dose
      dependent. CONCLUSION: PAPP-A may affect the function of vascular endothelial
      cells by reducing the secretion of NO and increasing the level of ET-1.

PMID- 21200095
TI  - [Association of serum follicle stimulating hormone with osteoprotegerin, leptin,
      TGF-beta1, and TGF-beta2 in women].
AB  - OBJECTIVE: To determine the relation between follicle-stimulating hormone (FSH)
      level and bone metabolism-related cytokines in women. METHODS: A cross-sectional
      study of 703 healthy Chinese women, aged 20-80 years, was conducted. Serum FSH,
      osteoprotegerin (OPG), leptin, transforming growth factor-beta 1 (TGF-beta1), and
      transforming growth factor-beta 2 (TGF-beta2) were detected. RESULTS: Serum FSH
      was positively correlated with OPG (r=0.447, P<0.01) and TGF-beta2 (r=0.344,
      P<0.01), and negatively correlated with TGF-beta1 (r=-0.374, P<0.01). After
      adjustment of age, a negative correlation was found between FSH and leptin (r=
      0.265, P<0.01). The multiple linear stepwise regression analysis showed that
      serum FSH was a negative determinant factor of TGF-beta1, and 22.6% changes in
      TGF-beta1 was determined by FSH. FSH was, however, a positive determinant factor
      of OPG and TGF-beta2, and 9.9% and 1.1% of the effect on OPG and TGF-beta2 was
      performed by FSH, respectively. Serum FSH almost had no effect on leptin.
      CONCLUSION: Serum FSH level in adult women is related to bone metabolism-related
      cytokines, such as TGF-beta1, OPG, and TGF-beta2.

PMID- 21200096
TI  - [Effect of alprostadil on hepatic injury of brain-dead rats and on serum TNF
      alpha and endothelin-1 expression].
AB  - OBJECTIVE: To study the effect of alprostadil lipid microballoons (lipo PGE1) on
      the function and morphous of livers from brain-dead rats. METHODS: Twenty-four SD
      rats were randomly assigned into 4 groups: a control group(Group C),a brain-dead
      group (Group B) and 2 lipo PGE1 protection groups (Group L1 and Group L2). Brain
      dead models were established in Group B,L1 and L2.There was no inflation of
      Fogarty balloon in Group C, while other operations were the same as Group B. Lipo
      PGE1 [20 ng/(kg.min) and 40 ng/(kg.min)] was injected via the femoral vein in
      Group L1 and Group L2 immediately after the establishment of the brain-dead
      model. The serum levels of alanine aminotransferase (ALT), aspartate amino
      transferase (AST), endothelin (ET)-1, and tumor necrosis factor (TNF)-alpha were
      detected by radioimmunological analyzer. Liver tissues were observed by HE
      staining 6 h after the brain death. RESULTS: At the time of brain death, the
      level of ALT, AST, ET-1, and TNF-alpha in Group B, L1 and L2 was significantly
      different compared with that in Group C. That in Group L1 and L2 was
      significantly lower than in Group B(P<0.05). There was no significant difference
      between Group L1 and L2(P>0.05). CONCLUSION: Brain death can cause damage to the
      liver of rats. Lipo PGE1 can relieve the injury of brain death donors.The
      protective mechanism of Lipo PGE1 is to decrease the release of serum
      inflammatory mediators.

PMID- 21200097
TI  - [Effect of ulinastatin on thromboxane B2 and deep vein thrombosis in elderly
      patients after hip joint replacement].
AB  - OBJECTIVE: To determine the effect of ulinastatin on plasma thromboxane B(2) and
      deep vein thrombosis(DVT) in elderly patients after hip joint replacement.
      METHODS: Eighty ASAI-IIpatients aged 65-81 years undergoing hip joint replacement
      were randomly divided into 4 groups (n=20): Group U1 (ulinastatin 5 000
      U/kg);Group U2 (ulinastatin 10 000 U/kg); Group U3 (ulinastatin 20 000 U/kg); and
      Group C (the same volume of saline as control).The blood samples were collected
      at 5 time points: preoperation (T(1)), immediately after the operation (T(2)), 1
      d (T(3)), 2 d (T(4)) and 3 d after the operation (T(5)), respectively.
      Thromboxane B(2) was detected, and DVT was also examined through color Doppler
      ultrasonography 3 d after the operation. RESULTS: Compared with T(1), the level
      of thromboxane B(2) significantly increased in Group C at T(2)-5, in Group U1 at
      T(2-4), in Group U2 and U3 at T(2) (P<0.01). Compared with Group C, the
      concentration of thromboxane B(2) decreased in Group U1 at T(2-3), in Group U2
      and U3 at T(2-4) (P<0.01). Compared with Group U1, thromboxane B(2) significantly
      decreased in Group U2 and U3 at T(2-4) (P<0.01).The incidence rate of DVT was 40%
      in Group C, 10% in Group U1. There was no incidence of DVT in the Group U2 and U3
      (P>0.05). CONCLUSION: Ulinastatin can inhibit blood thromboxane B(2) level in
      dose dependent manner and prevent DVT in elderly patients after hip joint
      replacement.

PMID- 21200098
TI  - [Clinical characteristics and operative effect of hippocampus lesions].
AB  - OBJECTIVE: To study the clinical characteristics and operative effect of
      hippocampus lesions. METHODS: We retrospectively analyzed the clinical
      characteristics and operative outcome of 44 patients with hippocampus lesions
      between August 2005 and April 2010. RESULTS: Seizure attack was the initial
      symptom among 40 of the 44 patients. Pathological examinations revealed 18
      gliomas, 9 cavernous malformations, 12 hippocampus sclerosis, 2 focal cortical
      dysplasia, 1 atypical hyperplasia, 1 injury glial scar, and 1 encephalomalacia.
      Thirteen patients received anterior medial temporal lobectomy and the other 31
      received lesionectomy or selective amygdalohippocampectomy via transsylvian
      approach. An average of 15.7 month follow-up was accomplished in 37 patients.
      Postoperative epileptic outcomes were evaluated according to Engel
      classification: Grade I 73.0%(27/37), Grade II 13.5%(5/37), Grade III 10.8%(4/37)
      and Grade IV 2.7%(1/37). No perioperative death occurred. One patient experienced
      hemiplegia but recovered 8 months after the operation. Noticeable postoperative
      visual field deficit was left in 2 patients. Two patients with glioma died of
      remote tumor recurrence during follow-up. CONCLUSION: Seizure attack is a major
      complaint of hippocampus lesions. Satisfactory seizure and tumor control may be
      achieved through anterior medial temporal lobectomy or selective
      amygdalohippocampectomy with lesionectomy.

PMID- 21200099
TI  - [Tumour-derived exosomes and their roles in cancer].
AB  - Exosomes are nanometer sized membrane vesicles, released in the extracellular
      milieu following the fusion of the external membrane of multivesicular body (MVB)
      with plasma membrane. They perform a certain function in immune regulation.
      Exosomes have been shown to be released by cells of hematopoietic and non
      hematopoietic origin. Tumour-derived exosomes (TEX) exist in the supernatant of
      tumour cells, plasma and malignant effusions of tumour patients. They contain
      native candidate tumour associated antigen and are capable of transferring
      antigens to T lymphocytes, therefore efficiently promoting cytotoxic T lymphocyte
      (CTL) activation and producing antitumor immunity. However, recent evidence shows
      that tumor exosomes may induce immunologic tolerance and even activate
      immunosuppression which makes tumour escape from the immune surveillance of the
      host immune system. In addition, tumor exosomes may mediate a growth-promoting
      effect on tumor cells. These discrepancies are almost certainly due to
      differences in the phenotype of the exosomes.

PMID- 21200100
TI  - Global cardiometabolic risk profile in patients with hypertension: results from
      the Turkish arm of the pan-European GOOD survey.
AB  - OBJECTIVES: We evaluated the results of the Turkish arm of the GOOD survey which
      investigated the cardiometabolic risk profile and the control of blood pressure
      (BP) of adult hypertensive outpatients in 12 countries across Europe. STUDY
      DESIGN: A total of 218 hypertensive patients (139 females, 79 males; mean age
      57.2+/-10.9 years) from Turkey were included in this pan-European survey. Blood
      pressure control (defined as BP <140/90 mmHg for nondiabetics and <130/80 mmHg
      for diabetics) and cardiometabolic risk factors such as diabetes mellitus,
      metabolic syndrome, obesity, sedentary lifestyle, and atherogenic dyslipidemia
      were evaluated in accordance with the 2003 ESH/ESC guidelines on management of
      hypertension. RESULTS: Control of BP was achieved in only 21.6% of the patients
      diagnosed with hypertension for a mean duration of 7.7+/-5.4 years. The mean
      systolic and diastolic BPs were 144+/-21 mmHg and 88+/-14 mmHg, respectively. The
      most frequent concomitant disease was type 2 diabetes mellitus (66 patients,
      30.3%). Patients with diabetes had a higher prevalence of metabolic syndrome
      compared to nondiabetics (78.8% vs. 48%, p<0.01). The absence of BP control was
      more pronounced among diabetics than in nondiabetics for systolic (77.3% vs.
      63.8%) and diastolic (84.9% vs. 57.2%) pressures. Nearly half of the hypertensive
      patients had atherogenic dyslipidemia, but only 35.8% of them were treated with
      lipid lowering drugs. CONCLUSION: Despite appropriate treatment, poor BP control
      in Turkish hypertensive patients was associated with metabolic syndrome,
      diabetes, and undertreatment of atherogenic dyslipidemia. Therefore, more
      effective measures must be taken in the management of cardiovascular risk factors
      to improve BP control.

PMID- 21200101
TI  - The relationship between saphenous coronary bypass graft occlusion and serum
      gamma-glutamyltransferase activity.
AB  - OBJECTIVES: Serum gamma-glutamyltransferase (GGT) activity has been shown to be
      associated with progression of atherosclerosis. We evaluated the relationship
      between serum GGT levels and saphenous vein bypass graft disease at least one
      year after coronary artery bypass graft (CABG) surgery. STUDY DESIGN: The study
      included 125 consecutive patients who had undergone CABG surgery with at least
      one saphenous vein graft (SVG) and were referred to cardiac catheterization for
      stable anginal symptoms or positive stress test results at least one year after
      CABG surgery. Laboratory parameters including serum GGT levels were measured
      before angiography. Occluded grafts were defined as a luminal stenosis of >=70%
      or absence of distal TIMI 3 flow. Thus, SVGs were found to be patent in 53
      patients (42.4%; 40 males, 13 females; mean age 65+/-8 years) and occluded in 72
      patients (57.6%; 62 males, 10 females; mean age 64+/-9 years). RESULTS: The two
      groups were similar with regard to age, gender, hypertension, diabetes mellitus,
      family history of coronary artery disease, smoking, and alcohol consumption. The
      mean time from CABG to angiography was similar in patients with a patent and
      occluded SVG (6.8+/-4.3 vs. 8.1+/-3.7 years; p>0.05). Waist circumference was
      greater (p=0.02) and serum levels of total cholesterol (p=0.001), triglyceride
      (p=0.02), uric acid (p<0.001), hs-CRP (p<0.001), GGT (p<0.001) and fibrinogen
      (p<0.001) were significantly higher in patients with occluded veins. Serum GGT
      level was moderately but significantly correlated with waist circumference
      (r=0.2, p=0.04), uric acid (r=0.3, p=0.008), and hs-CRP (r=0.3, p=0.002). In
      logistic regression analysis, total cholesterol (OR=1.012, 95% CI 1.002-1.023,
      p=0.03), hs-CRP (OR=1.968, 95% CI 1.17-3.311, 0.01), uric acid (OR=1.57, 95% CI
      1.1-2.208, p=0.01), and GGT (OR=1.047, 95% CI 1.002-1.1, p=0.04) were found to be
      significant predictors of SVG occlusion. CONCLUSION: Our results suggest that
      serum GGT activity is associated with higher occlusion rates of venous bypass
      grafts.

PMID- 21200102
TI  - The effects of endothelial dysfunction and inflammation on slow coronary flow.
AB  - OBJECTIVES: We evaluated the effects of endothelial dysfunction and inflammation
      on slow coronary flow (SCF). STUDY DESIGN: The study included 26 patients (group
      1; 13 females, 13 males; mean age 58.8 years) who had normal coronary arteries
      but SCF in three coronary vessels and 25 subjects (group 2, 14 females, 11 males;
      mean age 62.7 years) with normal coronary arteries and normal flow. Coronary flow
      was quantified according to the TIMI (Thrombolysis In Myocardial Infarction)
      frame count method for the left anterior descending (LAD), circumflex (Cx), and
      right coronary (RCA) arteries. Endothelial function was assessed by plasma
      asymmetric dimethylarginine (ADMA) levels, brachial artery endothelium-dependent
      flow-mediated dilatation (FMD), and nitroglycerin-mediated dilatation (NMD).
      Inflammation was assessed by high-sensitivity C-reactive protein (hs-CRP) levels.
      RESULTS: TIMI frame count was significantly higher in group 1 compared to group 2
      for each artery (p<0.001). In group 1, the mean FMD was significantly lower
      (6.6+/-1.6% vs. 11.2+/-1.6%, p<0.001) and the mean ADMA level was significantly
      higher (0.8+/-0.2 umol/l vs. 0.5+/-0.1 umol/l, p=0.002), whereas NMD and hs-CRP
      levels did not differ significantly between the two groups (p>0.05). There was a
      significant correlation between plasma ADMA level and TIMI frame count (RCA:
      r=0.50, p=0.001; cLAD: r=0.46, p=0.004; Cx: r=0.32, p=0.04) and a significant
      negative correlation between FMD and TIMI frame count (cLAD: r=-0.68, p=0.0003;
      Cx: r=-0.54, p=0.0004; RCA: r=-0.46, p=0.004), but hs-CRP level was not
      correlated with TIMI frame count. In multivariate analysis, only ADMA (p=0.009)
      and FMD (p=0.02) were significant parameters to predict SCF. CONCLUSION: Our
      results suggest that endothelial dysfunction as determined by increased ADMA
      level and impaired FMD, rather than inflammation, plays a role in the
      etiopathogenesis of SCF.

PMID- 21200103
TI  - [Levosimendan and dobutamine have a similar profile for potential risk for
      cardiac arrhythmias during 24-hour infusion in patients with acute decompensated
      heart failure].
AB  - OBJECTIVES: Unlike traditional inotropic agents, levosimendan is thought to have
      a lower potential to induce arrhythmias because it does not increase
      intracellular calcium levels and myocardial oxygen consumption. We compared the
      potential effect of levosimendan and dobutamine to induce cardiac arrhythmias in
      patients with decompensated heart failure. STUDY DESIGN: Fifty patients with
      acute decompensated heart failure (NYHA class III-IV, ejection fraction <35%) who
      were in need of inotropic support were randomized to dobutamine (n=25; mean age
      69+/-10 years) or levosimendan (n=25; mean age 67.5+/-11.5 years) and underwent
      24-hour Holter monitoring before and during inotropic infusion. Holter recordings
      were analyzed with respect to heart rate (HR), ventricular premature contraction
      (VPC), couplets of VPC, supraventricular premature contraction (SVPC), paroxysmal
      atrial fibrillation (PAF), and nonsustained ventricular tachycardia (NSVT).
      RESULTS: Before infusions, the two groups were similar with respect to HR, VPC,
      couplets of VPC, SVPC, and PAF episodes, but the number of NSVT episodes was
      significantly higher in the levosimendan group. Heart rate and the number of VPCs
      increased significantly during infusions of levosimendan (p=0.036 and p<0.001,
      respectively) and dobutamine (for both p<0.001). Increase in couplets of VPC was
      significant only with dobutamine (p=0.012). The episodes of NSVT and PAF
      increased with levosimendan, without reaching significance. Levosimendan and
      dobutamine groups were similar in terms of percentage changes in arrhythmias
      (55+/-224% vs. 11+/-16% for VPC; 2+/-2.7% vs. 12+/-9% for couplets of VPC; 3.4+/
      5.8% vs. 16+/-39% for SVPC, 0.4+/-2.8% vs. -2+/-0% for NSVT) and percentage
      change in total arrhythmias (41+/-190% vs. 18+/-35.4%), and the mean HR, VPC,
      couplets of VPC, SVPC, and episodes of NSVT and PAF (p>0.05). CONCLUSION: Our
      findings suggest that levosimendan and dobutamine have a similar profile for
      potential risk for cardiac arrhythmias.

PMID- 21200104
TI  - [The prevalence of coronary artery anomalies in patients undergoing multidetector
      computed tomography for the evaluation of coronary artery disease].
AB  - OBJECTIVES: Coronary artery anomalies (CAA) can be detected by multidetector
      computed tomography (MDCT) with a high accuracy. The purpose of this study was to
      evaluate the prevalence of CAA in subjects undergoing MSCT coronary angiography
      for the assessment of coronary artery disease. STUDY DESIGN: This retrospective
      study included 1,056 patients (534 males, 522 females; mean age 58.8+/-11.5
      years) who underwent coronary dual-source 64-slice MDCT for the assessment of
      coronary artery disease. Coronary angiographic scans were obtained with injection
      of 80 ml nonionic contrast medium. Retrospective gating technique was used to
      synchronize data reconstruction with the ECG signal. The reconstructions were
      obtained in all cardiac phases at 50-millisecond intervals at a slice thickness
      of 0.75 mm and a reconstruction increment of 0.5 mm. Maximum intensity
      projection, multiplanar reformatted, and volume rendering images were derived
      from axial scans. RESULTS: Eleven patients (1.04%) were found to have a CAA.
      These included high take-off of the left main coronary artery (LMCA) (n=3, 0.3%),
      absence of the LMCA (n=3, 0.3%), coronary fistula (n=2, 0.2%), right-sided origin
      of the circumflex artery (n=2, 0.2%), and left anterior descending artery
      originating from the right coronary artery (n=1, 0.1%). CONCLUSION: Multidetector
      computed tomography is a reliable and useful noninvasive method to identify and
      define anomalous coronary arteries and their course and can be used as the first
      line diagnostic tool in the evaluation of CAAs.

PMID- 21200105
TI  - Acute pericarditis and transient erythroblastopenia associated with human
      parvovirus B19 infection.
AB  - We report on an eight-year-old girl with acute pericarditis and transient
      erythroblastopenia associated with human parvovirus B19 (PVB19) infection. The
      patient presented with complaints of fever, chest pain, fatigue, and shortness of
      breath. On physical examination, she had tachycardia, hepatomegaly, and muffled
      heart sounds. Teleradiography exhibited cardiomegaly and echocardiography showed
      a pericardial effusion of 25 mm. Serum anti-PVB19 IgM and PVB19 DNA were
      positive. The patient developed anemia and reticulocytopenia in the second week,
      both of which persisted for two weeks then resolved spontaneously. At the end of
      three months, pericardial effusion resolved, hemoglobin and hematocrit levels
      were normal, and serum anti-PVB19 IgM was negative. This case represents the
      first report of acute pericarditis associated with PVB19 infection in a pediatric
      patient.

PMID- 21200106
TI  - Electromagnetic interference with electrocardiogram recording of exercise test
      equipment.
AB  - Herein, we report a case of pseudosinus tachycardia resulting from an
      electromagnetic interference between a mobile phone and treadmill device.
      Electromagnetic interference from a charging mobile phone connected to the same
      socket with the exercise device turned the recording of a patient to that of
      pseudosinus tachycardia at approximately twice the rate of actual basal heart
      rate. Removal of the mobile phone from the socket resulted in normalization of
      the electrocardiogram.

PMID- 21200107
TI  - Migration of the breakthrough: the advantage of noncontact mapping in targeting
      inappropriate sinus tachycardia.
AB  - We report on a 42-year-old female patient with inappropriate sinus tachycardia
      (IST), in whom an effective sinus node modification was made by using the
      noncontact mapping system. The patient was admitted with palpitations and a heart
      rate between 90-110 beats per minute (bpm). Her heart rate increased to 150 bpm
      during minimal exercise. After confirming the diagnosis of IST by an
      electrophysiological study, radiofrequency catheter ablation was performed. A
      color-coded isopotential map was created when the heart rate was 95 bpm and the
      initial breakthrough of the sinus node (SNB) was labeled. After administration of
      isoproterenol, a new color-coded map recording was created when the heart rate
      reached 160 bpm, showing a new breakthrough 24 mm away from the SNB.
      Radiofrequency was delivered to this region and the heart rate decreased to 120
      bpm. After another infusion of isoproterenol, the maximum heart rate reached 140
      bpm and another isopotential map recording was created, which demonstrated
      migration of the breakthrough 16 mm away from the SNB. Radiofrequency was
      delivered to the second site and the heart rate decreased to 90 bpm and increased
      to a maximum of 120 bpm after a new isoproterenol infusion. A subsequent infusion
      caused no increase in the heart rate, and the ablation procedure was terminated.
      During a follow-up of one year, the patient was in sinus rhythm with a mean heart
      rate of 80 bpm.

PMID- 21200108
TI  - Severe hemodynamic compromise due to left atrial compression by a dissecting
      aortic aneurysm.
AB  - Hemodynamically compromising left atrial (LA) compression by an aortic aneurysm
      is a rare entity. An 83-year-old woman with a previous diagnosis of congestive
      heart failure was admitted with worsening shortness of breath (NYHA grade III)
      and palpitations. The electrocardiogram showed atrial fibrillation. The chest X
      ray revealed widening of the mediastinum and congested lung fields. Transthoracic
      echocardiography demonstrated LA compression by a large descending thoracic
      aortic aneurysm. Left and right ventricle systolic functions were preserved.
      Thoracic three-dimensional magnetic resonance imaging showed LA compression by a
      descending aortic aneurysm and an intramural hematoma. No intimal flap was seen
      in any part of the thoracic aorta. Emergency surgery was planned, but the patient
      did not accept surgery and suddenly died after four days of admission. Focal
      descending aortic aneurysm with an intramural hematoma in the aortic wall causing
      nearly complete obliteration of the LA cavity has not been reported before.

PMID- 21200109
TI  - [Incomplete pacemaker lead fracture revealed by superficial maneuvers].
AB  - A 75-year-old man presented to our department with a complaint of recurrent
      syncope episodes seven years after dual chamber pacemaker implantation due to
      complete atrioventricular block. His electrocardiogram obtained on presentation
      showed a normal dual-chamber pacemaker rhythm. The chest X-ray and pacemaker
      interrogation did not show any lead fracture or dysfunction. Twenty-four hour
      Holter monitoring revealed periods of failure to pacing. Superficial maneuvers
      over the skin resulted in an excessive increase in the ventricular lead impedance
      and pacing failure. The clinical course of the patient was uneventful after
      implantation of a new electrode to the right ventricular apex.

PMID- 21200110
TI  - [Transcatheter closure of atrial septal defects in a patient with lipomatous
      hypertrophy of the interatrial septum].
AB  - Lipomatous hypertrophy of the interatrial septum is a rare benign pathology
      characterized by fatty deposits in the septum and is mostly diagnosed
      incidentally. This accumulation mostly causes a globular thickening of the
      interatrial septum, commonly sparing the fossa ovalis. We report on a 65-year-old
      female patient who underwent successful transcatheter closure of atrial septal
      defects (ASD) accompanied by lipomatous hypertrophy of the septum. Both
      transthoracic and transesophageal echocardiography showed enlargement of the
      right heart cavities, thickening of the interatrial septum (16 mm) with bright
      echogenicity, and two separate secundum ASDs measuring 17 mm and 4 mm,
      respectively. Transcatheter closure of the defects was performed using a 24-mm
      Amplatzer septal occluder. There was no residual shunt and Holter monitoring was
      normal after the procedure. During a three-year follow-up, no complications were
      observed pertaining to the procedure or lipomatous tissue.

PMID- 21200111
TI  - [Novel agents in antiplatelet therapy].
AB  - Antiplatelet therapy is the cornerstone of management of acute coronary
      syndromes. Currently used antiplatelet drugs present several limitations that
      provoke new searches. These limitations include resistance, delay in the onset of
      action, risk for bleeding, variations in the individual response, and interaction
      with other medications (i.e. proton pump inhibitors, calcium channel blockers).
      New concepts and medications have emerged for the effective inhibition of
      platelets. Prasugrel, AZD6140 (ticagrelor), cangrelor, and SCH 530348 (thrombin
      receptor antagonist) are among some of the novel agents that survived randomized
      trials. In this review, we aimed to summarize novel concepts and agents in
      antiplatelet therapy.

PMID- 21200112
TI  - Case images: a pericardial cyst due to familial Mediterranean fever.

PMID- 21200113
TI  - Case images: free-floating thrombus in the right atrium, ventricle, and outflow
      tract effectively treated with thrombolysis.

PMID- 21200114
TI  - Intermittent severe tricuspid stenosis caused by myxoma originating from the free
      wall of the right atrium.

PMID- 21200115
TI  - [Case images: pulmonary artery thrombus with an atypical appearance: computed
      tomography findings].

PMID- 21200116
TI  - [Evaluation of hospitalization period and five-year follow-up of patients
      admitted with acute coronary syndrome following coronary artery bypass graft
      surgery].
AB  - OBJECTIVES: We evaluated patients admitted with the diagnosis of acute coronary
      syndrome (ACS) after coronary artery bypass graft (CABG) surgery. STUDY DESIGN:
      This retrospective study included 72 consecutive CABG patients (10 women, 62 men;
      mean age 63+/-9 years; range 45 to 83 years). Acute coronary syndrome was defined
      as the presence of unstable angina or myocardial infarction (MI) with or without
      ST elevation. Time from CABG surgery to admission with ACS was defined as bypass
      age. Following discharge, information was derived by phone calls from the
      patients or relatives on cardiovascular events within a five-year period.
      RESULTS: On admission, 14 patients (19.4%) had non-ST elevation MI, nine patients
      (12.5%) had ST elevation MI, and 49 patients (68.1%) had unstable angina. The
      mean bypass age was 5.6+/-3.5 years. Of the study group, 38.9% were obese, 25%
      were diabetic, 54.2% were hypertensive, 44.4% were hyperlipidemic, and 26.4% were
      current smokers. Medications before admission included aspirin (81.9%), statin
      (25%), beta-blocker (27.8%), ACE inhibitor or angiotensin receptor blocker
      (27.8%), and calcium channel antagonist (36.1%). Increased LDL cholesterol (>=100
      mg/dl) and decreased HDL cholesterol (<=50 mg/dl) levels were present in 55.6%
      and 80.6%, respectively. Mortality occurred in 15 patients, four during
      hospitalization, and 11 after discharge. The overall mortality rate was 21.4%. In
      correlation analysis, mortality was positively correlated with age (r=0.34,
      p=0.005), bypass age (r=0.37, p=0.001), CRP level (r=0.31, p=0.033) and
      negatively correlated with beta-blocker use (r=-0.25, p=0.041) and ejection
      fraction (r=-0.37, p=0.016). CONCLUSION: Our results show that, following CABG
      surgery, special consideration should be given to risk factor management and use
      of agents with proven effects against cardiovascular mortality such as statins,
      beta-blockers, and ACE inhibitors.

PMID- 21200117
TI  - [Preferences regarding invasive diagnostic procedures in patients aged 70 years
      or over presenting with acute coronary syndrome and relationship with short-term
      mortality].
AB  - OBJECTIVES: We prospectively classified patients presenting with acute coronary
      syndrome (ACS) into two age groups, <70 years and >=70 years, and investigated
      the frequency of cardiac catheterization, the predictors of cardiac
      catheterization in the older patient population, and determined early mortality
      in patients treated with or without cardiac catheterization. STUDY DESIGN: The
      study included 1,101 patients admitted with ACS. The patients were prospectively
      classified in two age groups, <70 years (n=762; mean age 55+/-9 years) and >=70
      years (n=339; mean age 76+/-5 years). Data on demographic characteristics,
      clinical and laboratory findings, and the presence or absence of cardiac
      catheterization were recorded. The predictors of cardiac catheterization were
      assessed in the overall patient group and in those >=70 years of age, and 30-day
      mortality rates were determined. RESULTS: Compared with the older group, in
      younger patients cardiac catheterization was more frequent (74.4% vs. 50.7%,
      p=0.0001) and earlier (p=0.023), and decision for percutaneous coronary
      intervention was more common (52.7% vs. 40.7%, p=0.010), whereas coronary bypass
      grafting was performed more frequently in the older group (43% vs. 31.2%,
      p=0.010). Overall 30-day mortality rates showed significant differences in both
      groups between patients treated with or without cardiac catheterization (<70
      years: 3.7% vs. 18.3%, p<0.0001; >=70 years: 5.6% vs. 21%, p<0.0001). Logistic
      regression analysis showed the following as significant predictors of cardiac
      catheterization in patients >=70 years of age: heart failure (OR: 3.853,
      p=0.017), systolic blood pressure <100 mmHg (OR: 3.602, p=0.008), creatinine
      clearance <60 ml/min (OR: 2.761, p=0.001), and ST-segment elevation >=1 mm on the
      electrocardiogram (OR: 2.817, p=0.0001). CONCLUSION: Invasive diagnostic and
      therapeutic strategies are implemented less frequently in elderly patients. These
      procedures, which offer obvious mortality benefit, should be considered in
      elderly patients after meticulous risk evaluation.

PMID- 21200118
TI  - Diastolic functions and myocardial performance index in obese patients with or
      without metabolic syndrome: a tissue Doppler study.
AB  - OBJECTIVES: This study was designed to evaluate left ventricular (LV) diastolic
      functions and myocardial performance index (MPI) in obese individuals with or
      without metabolic syndrome (MetS). STUDY DESIGN: The study included 44 obese
      subjects with MetS (16 men; 28 women; mean age 46+/-7 years) and 32 obese
      subjects without MetS (16 men, 16 women; mean age 43+/-9 years). Diagnosis of
      MetS was based on the ATP III criteria. Obesity was defined with a body mass
      index (BMI) of >=30 kg/m2. All the subjects underwent echocardiography and tissue
      Doppler imaging to determine LV diastolic functions and MPI. Clinical and
      echocardiographic characteristics of obese subjects were compared with those of a
      control group consisting of 21 healthy, nonobese individuals (10 men, 11 women;
      mean age 42+/-4 years). RESULTS: Waist circumference, weight, and BMI were
      similar in the two obese groups. Control subjects and obese subjects without MetS
      had similar systolic and diastolic blood pressures, fasting blood glucose,
      triglyceride, and HDL cholesterol levels, but all these significantly differed in
      patients with MetS. Left ventricular mass, mass index, and diastolic parameters
      were similar in the two obese groups, but differed significantly from the
      controls (p<0.05). Body mass index was correlated with the LV mass (r=0.42,
      p=0.001) and mass index (r=0.33, p=0.001). Left ventricular MPI was similar in
      the two obese groups with (0.59+/-0.10) and without (0.59+/-0.11) MetS, but was
      higher compared to the control group (0.48+/-0.06, p<0.05). Left ventricular MPI
      was correlated with BMI, waist circumference, LV mass, and mass index (r=0.24,
      p=0.02; r=0.30, p=0.005; r=0.31, p=0.002; r=0.21, p=0.04, respectively).
      CONCLUSION: Our findings demonstrate that obesity with or without MetS affects LV
      MPI. In addition, LV MPI showed significant correlations with BMI, waist
      circumference, and LV mass.

PMID- 21200119
TI  - Relationship between HbA1c and coronary flow rate in patients with type 2
      diabetes mellitus and angiographically normal coronary arteries.
AB  - OBJECTIVES: We examined the relationship between glycosylated hemoglobin (HbA1c)
      level and coronary flow rate in patients with type 2 diabetes mellitus (DM) and
      angiographically normal coronary arteries. STUDY DESIGN: The study included 54
      consecutive patients (36 males, 18 females; age range 37 to 72 years) with type 2
      DM, whose coronary arteries were found normal on coronary angiography. All
      patients underwent echocardiography and plasma HbA1c levels were measured before
      coronary angiography. To determine slow coronary flow (SCF), coronary flow rates
      of the left anterior descending (LAD), circumflex (Cx), and right coronary (RCA)
      arteries were assessed using the TIMI frame count (TFC) method. RESULTS: None of
      the patients had echocardiographic abnormalities. The mean HbA1c level was 7.4+/
      2.0%, and the mean TFCs were 34.3+/-6.5, 22.4+/-3.5, and 20.4+/-2.2 for the LAD,
      Cx, and RCA, respectively. HbA1c levels were <7% in 26 patients, and >=7% in 28
      patients. Thirty-eight patients (70.4%) were found to have SCF in at least one
      coronary artery. TIMI frame counts of all three coronary arteries were
      significantly greater in patients in whom HbA1c was >=7% (p<0.001). TIMI frame
      counts showed significant correlations with the HbA1c level (LAD: r=0.782; Cx:
      r=0.707; RCA: r=0.515; p<0.001 for all). The mean HbA1c level was significantly
      higher in patients with SCF compared to patients without SCF (7.8+/-1.9% vs.
      5.6+/-0.9%; p<0.001). The incidence of SCF was significantly greater in patients
      with HbA1c >=7.0% than those with HbA1c <7.0% (96.4% vs. 61.5%; p=0.004).
      Increased HbA1c (>=7%) significantly increased the risk for SCF in at least one
      coronary artery (OR=16.875; 95% CI 1.972-144.38). CONCLUSION: Our findings
      suggest that there is a strong correlation between the HbA1c level and coronary
      flow rate.

PMID- 21200120
TI  - Anomalous origin of one pulmonary artery branch from the ascending aorta:
      experience of our center.
AB  - OBJECTIVES: Anomalous origin of one pulmonary artery branch from the aorta in the
      presence of separate aortic and pulmonary valves is a rare but important entity
      necessitating early diagnosis and surgery to prevent irreversible vascular
      pulmonary disease. We evaluated our experience with seven infants having this
      anomaly. STUDY DESIGN: Between December 2003 and 2009, a total of seven infants
      (2 girls, 5 boys, age range 4 days to 84 days) were diagnosed as having anomalous
      origin of one pulmonary artery branch from the aorta. Clinical records were
      reviewed for clinical features, operative procedures, and postoperative follow
      up. RESULTS: Common symptoms were dyspnea, tachypnea, and poor feeding. All the
      cases were diagnosed by echocardiography. The right pulmonary artery in six cases
      and the left pulmonary artery in one case originated from the ascending aorta. In
      addition, three patients had patent ductus arteriosus (PDA), five patients had
      patent foramen ovale, and one patient had interruption of the aortic arch and
      aortopulmonary window. All patients underwent surgical re-implantation of the
      anomalous pulmonary artery branch to the pulmonary trunk. Associated surgical
      procedures included PDA ligation in three patients, and total repair of
      interrupted aortic arch and aortopulmonary window in one patient. There were no
      in-hospital deaths. Two patients had prolonged intubation (10 and 16 days). All
      patients were discharged in good clinical condition. During a follow-up period
      ranging from two months to six years, only one patient developed stenosis at the
      site of anastomosis. CONCLUSION: Prompt diagnosis at infancy, improved surgical
      technique, and good patient care decrease mortality and morbidity associated with
      anomalous origin of the pulmonary artery from the aorta.

PMID- 21200121
TI  - An intercoronary connection serving as a safety valve for the left ventricle.
AB  - Intercoronary connection is an infrequent finding during coronary angiography and
      may serve as a safety valve for compromised coronary circulation. A 60-year-old
      woman with hyperlipidemia was admitted with stable angina pectoris of one-year
      history. Physical examination including cardiac auscultation was normal. The
      electrocardiogram showed no ischemic changes. Transthoracic echocardiography
      showed no wall motion abnormality and she had normal ejection fraction. Coronary
      angiography showed total occlusion of the proximal portion of the left anterior
      descending (LAD) artery and severe occlusion of the circumflex artery. Selective
      right coronary angiography showed no stenosis, with anterograde filling of the
      right coronary artery (RCA) and retrograde filling of the LAD through the RCA.
      The totally occluded LAD was in communication with the distal RCA through a large
      lumen as a single conduit whose diameter was equal to that of the distal LAD.
      Left ventriculography showed no abnormality. Because of the retrograde filling of
      the LAD with TIMI III flow, grafting of the LAD was not considered. The patient
      underwent successful bare metal stent implantation in the circumflex artery and
      was discharged free of chest pain on medical treatment.

PMID- 21200122
TI  - Ruptured sinus of Valsalva aneurysm associated with aortic regurgitation and
      severe myocardial ischemia.
AB  - Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly either presenting as a
      congenital heart disease or occurring secondary to cardiac surgical
      interventions. A 19-year-old male patient presented with chest pain and shortness
      of breath. On auscultation, a grade 4/6 early diastolic murmur was heard over the
      left lower sternal border and Erb's area with a thrill. Crepitating rales were
      heard over bilateral basal lung fields. The electrocardiogram showed right bundle
      branch block and ST depression. Troponin and CK-MB levels were increased. Shortly
      after admission, he developed ventricular fibrillation and was defibrillated
      three times. After restoration of hemodynamic stabilization, transthoracic
      echocardiography was performed, which showed grade 4 aortic regurgitation, patent
      foramen ovale, and an aneurysm of the sinus of Valsalva arising from the right
      coronary sinus, with rupture into the right ventricle. The patient underwent
      surgery under cardiopulmonary bypass, for repair of the ruptured SVA and patent
      foramen ovale and aortic valve replacement. He was discharged on the fifth
      postoperative day following an uneventful operation and postoperative course.

PMID- 21200123
TI  - Late bare metal stent thrombosis.
AB  - Late stent thrombosis is very rare in bare metal stents. We report on a 72-year
      old male patient who developed late thrombosis of a bare metal stent implanted in
      the left main coronary artery (LMCA). The patient presented with cardiogenic
      shock 350 days after the first stent implantation. Coronary angiography showed
      total occlusion of the stent. Following the first balloon predilatation of the
      lesion, a flow in the LMCA was observed, but there was no flow in the left
      anterior descending (LAD) artery. Then, a bare metal stent was implanted into the
      LAD. Although the flow was maintained and all inotropic support continued,
      hypotension persisted. Angiography of the right coronary artery demonstrated 90%
      stenosis at the same location which had been observed as a noncritical lesion
      during the first percutaneous coronary intervention. As the patient was in shock,
      the right coronary artery was also stented and TIMI 3 flow was obtained. However,
      the patient developed cardiac arrest and died despite repeated efforts of
      cardiopulmonary resuscitation. It was learned that the patient had undergone an
      urological operation for bladder stone nine days before, for which both aspirin
      and clopidogrel were discontinued six days before the operation. Only aspirin was
      reinitiated three days after the procedure. He then presented to our hospital
      with cardiogenic shock on his first day after discharge.

PMID- 21200124
TI  - Retained pericardial pellets for 25 years: a case report.
AB  - Retained cardiac pellets are clinically silent foreign bodies that do not cause
      any cardiovascular disturbance. A 71-year-old woman presented with exertional
      chest pain. Her physical examination and surface electrocardiogram were normal.
      After a positive treadmill test, coronary angiography was performed which showed
      nonsignificant coronary lesions. During fluoroscopy, several pellets were
      observed throughout the neck and two of them were simultaneously moving within
      the heart shadow. Transthoracic and transesophageal echocardiography showed no
      evidence for pericardial effusion. Computed tomography scans of the chest showed
      the pellets above the left diaphragm in the pericardial area. Her past medical
      history revealed an accidental shot from a pellet rifle by her son 25 years
      before, at which time no surgical intervention was planned as she had been
      asymptomatic.

PMID- 21200125
TI  - Hemolysis and infective endocarditis in a mitral prosthetic valve.
AB  - Traumatic intravascular hemolysis after heart valve replacement can be a serious
      problem. It is commonly associated with either structural deterioration or
      paravalvular leaks. A 63-year-old woman with a six-year history of surgery for
      mitral stenosis presented with complaints of weakness and dyspnea. She received
      treatment at other centers three times in the past six months for dyspnea and
      anemia requiring transfusion of red blood cells. Transthoracic echocardiography
      showed a normally functioning mitral mechanic prosthesis. Laboratory findings
      were abnormal for hemoglobin, hematocrit, white blood cell count, C-reactive
      protein, serum haptoglobin, and lactate dehydrogenase. Peripheral blood smear
      showed marked schistocytes, indicative of mechanical erythrocyte destruction.
      Transesophageal echocardiography demonstrated severe paravalvular leak and a
      large (9x13 mm) vegetation adhering to the prosthetic valve, protruding into the
      left atrium. Enterococcus faecalis was isolated from blood cultures. Surgery was
      planned because of large vegetation, repeated hemolysis, and severe paravalvular
      regurgitation, but the patient refused surgical treatment.

PMID- 21200126
TI  - [Repeated prolonged thrombolytic therapy after unsuccessful thrombolysis in
      massive pulmonary embolism: a case report].
AB  - We report on a 43-year-old woman who presented with shortness of breath and
      syncope due to massive pulmonary embolism. Transthoracic echocardiography showed
      signs of right ventricular overload, and contrast-enhanced chest computed
      tomography demonstrated filling defects in both main pulmonary arteries
      consistent with obstructing thrombi. Initially, thrombolytic therapy with
      recombinant tissue plasminogen activator was given, but shock was not resolved.
      Thrombolytic therapy was repeated with streptokinase and infusion was extended to
      48 hours, which yielded a successful result without any hemorrhagic complication.
      Repeated prolonged thrombolytic therapy after initial unsuccessful thrombolysis
      can be considered an alternative option in massive pulmonary embolism.

PMID- 21200127
TI  - [The microvolt T-wave alternans test].
AB  - Several clinical parameters and noninvasive tests have been developed to identify
      patients under the risk for sudden cardiac death (SCD). The microvolt T-wave
      alternans (MTWA) test is a noninvasive diagnostic method based on the measurement
      of subtle (microvolt) beat-to-beat alternation of the T-wave on the surface
      electrocardiogram and used for risk stratification of patients under the risk for
      SCD. Studies in the last decade have shown that the MTWA test is an effective
      method to distinguish patients with a high risk for arrhythmogenic mortality
      among patients suffering ischemic or nonischemic cardiomyopathies or with a
      history of myocardial infarction, with a high negative predictive value. This
      review revisits the MTWA test in the light of the most recent clinical studies.

PMID- 21200128
TI  - [Large interatrial septal aneurysm].

PMID- 21200129
TI  - [Bicuspid aortic valve endocarditis associated with aortic root abscess and aorta
      left atrium fistulization].

PMID- 21200130
TI  - [Two sisters with Jervell-Lange- Nielsen syndrome].

PMID- 21200131
TI  - Visualization of the geometric profile of the septal occluder by real-time 3D
      transesophageal echocardiography after closure of an atrial septal defect.

PMID- 21200132
TI  - Successful device closure of two separate atrial septal defects under the
      guidance of 3D transesophageal echocardiography.

PMID- 21200133
TI  - Ligation of CD40 receptor in human B lymphocytes triggers the 5-lipoxygenase
      pathway to produce reactive oxygen species and activate p38 MAPK.
AB  - Previously, we reported that CD40-induced production of reactive oxygen species
      (ROS) by NADPH oxidase requires the TNF receptor-associated factor (TRAF) 3, as
      well as the activities of phosphatidylinositol 3-kinase (PI3K) and Rac1. Here we
      investigated the possible mechanisms of the production of ROS after CD40 ligation
      in B cells. We describe an alternative ROS production pathway that is triggered
      by CD40 ligation, involves 5-lipoxygenase (5-LO), and results in activation of
      p38 MAPK. Our studies in Raji human B lymphomas revealed that CD40-induced ROS
      production by 5-LO also requires the activities of PI3K and Rac1. In contrast to
      the NADPH oxidase pathway, however, TRAF molecules are not required for the CD40
      induced ROS production by 5-LO. The association of CD40 with 5-LO is dependent on
      CD40 ligation in Raji B cells, and co-immunoprecipitation experiments using
      epitope- tagged proteins transiently expressed in human embryonic kidney 293T
      cells revealed the role of the regulatory subunit of PI3K, p85, in this
      association. Collectively, these data suggest a separate pathway for the CD40
      induced ROS production in B cells and demonstrate that this pathway requires 5-LO
      via direct association of p85 with both CD40 and 5-LO.

PMID- 21200134
TI  - AGR2, a mucinous ovarian cancer marker, promotes cell proliferation and
      migration.
AB  - Ovarian cancer is a leading cause of death in women. Early detection of ovarian
      cancer is essential to decrease mortality. However, the early diagnosis of
      ovarian cancer is difficult due to a lack of clinical symptoms and suitable
      molecular diagnostic markers. Thus, identification of meaningful tumor biomarkers
      with potential clinical application is clearly needed. To search for a biomarker
      for the early detection of ovarian cancer, we identified human anterior gradient
      2 (AGR2) from our systematic analysis of paired normal and ovarian tumor tissue
      cDNA microarray. We noted a marked overexpression of AGR2 mRNA and protein in
      early stage mucinous ovarian tumors compared to normal ovarian tissues and serous
      type ovarian tumors by Western blot analysis and immunohistochemistry. To further
      elucidate the role of AGR2 in ovarian tumorigenesis, stable 2774 human ovarian
      cancer cell lines overexpressing AGR2 were established. Forced expression of AGR2
      in 2774 cells enhanced the growth and migration of ovarian cancer cells. AGR2
      protein was detected in the serum of mucinous ovarian cancer patients by Western
      blot and ELISA analysis. Thus, AGR2 is a potential biomarker for the diagnosis of
      mucinous ovarian cancer and an ELISA assay may facilitate the early detection of
      mucinous ovarian cancer using patient serum.

PMID- 21200135
TI  - Central role for cAMP signaling in pigmentation and UV resistance.

PMID- 21200136
TI  - Cell death by sugar: bittersweet TOR.

PMID- 21200137
TI  - C. elegans seam cells as stem cells: Wnt signaling and casein kinase Ialpha
      regulate asymmetric cell divisions in an epidermal progenitor cell type.

PMID- 21200138
TI  - The importance of being in the right place at the right time: overexpression of
      Cdk2 and its ortholog Ime2 are toxic to S. cerevisiae.

PMID- 21200139
TI  - A new regulator of the cell cycle: the PR-Set7 histone methyltransferase.
AB  - The ability of eukaryotes to alter chromatin structure and function is modulated,
      in part, by histone-modifying enzymes and the post-translational modifications
      they create. One of these enzymes, PR-Set7/Set8/KMT5a, is the sole histone
      methyltransferase responsible for the monomethylation of histone H4 lysine 20
      (H4K20me1) in higher eukaryotes. Both PR-Set7 and H4K20me1 were previously found
      to be tightly cell cycle regulated suggesting that they play an important,
      although unknown, role in cell cycle progression. Several recent reports reveal
      that PR-Set7 abundance is dynamically regulated during different cell cycle
      phases by distinct enzymes including cdk1/cyclinB, Cdc14, SCF(Skp2), CRL4(cdt2)
      and APC(cdh1). Importantly, these reports demonstrate that inappropriate levels
      of PR-Set7 result in profound cell cycle defects including the inability to
      initiate S phase, the re-replication of DNA and the improper timing of mitotic
      progression. Here, we summarize the significance of these new findings, raise
      some important questions that require further investigation and explore several
      possibilities of how PR-Set7 and methylated H4K20 may likely function as novel
      regulators of the cell cycle.

PMID- 21200140
TI  - A role for CDK9-cyclin K in maintaining genome integrity.
AB  - Cyclin-dependent kinase 9 (CDK9), with its cyclin T regulatory subunit, is a
      component of the positive transcription elongation factor b (P-TEFb) complex,
      which stimulates transcription elongation and also functions in co
      transcriptional histone modification, mRNA processing, and mRNA export. CDK9 also
      binds to cyclin K but the function of this CDK9-cyclin K complex is less clear.
      We and others have recently shown that CDK9 functions directly in maintaining
      genome integrity. This activity is restricted to CDK9-cyclin K. Depletion of CDK9
      or its cyclin K but not cyclin T regulatory subunit impairs cell cycle recovery
      in response to replication stress and induces spontaneous DNA damage in
      replicating cells. CDK9-cyclin K also interacts with ATR and other DNA damage
      response and DNA repair proteins. CDK9 accumulates on chromatin and limits the
      amount of single-stranded DNA in response to replication stress. Collectively,
      these data are consistent with a model in which CDK9 responds to replication
      stress by localizing to chromatin to reduce the breakdown of stalled replication
      forks and promote recovery from replication arrest. The direct role of CDK9
      cyclin K in pathways that maintain genome integrity in response to replication
      stress appear to be evolutionarily conserved.

PMID- 21200141
TI  - Beyond effector caspase inhibition: Bcl2L12 neutralizes p53 signaling in
      glioblastoma.
AB  - Malignant gliomas are the most common and lethal primary central nervous system
      cancer. Glioblastoma mutliforme (GBM), the most aggressive of these neoplasms,
      are generally lethal within 2 years of diagnosis due in part to the intense
      apoptosis resistance of its cancer cells, hence poor therapeutic response to
      conventional and targeted therapies.  Twenty years of research has uncovered key
      genetic events involved in disease initiation and progression, foremost the Tp53
      tumor suppressor that is mutated or deleted in 35% of GBM. The prime importance
      of p53 signaling for gliomapathogenesis is further evidenced by epistatic genetic
      events targeting additional pathway components including deletion of p14 (Arf)
      (CDKN2A) and amplification of the p53-degrading ubiquitin ligases MDM2 and MDM4. 
      Recent studies have identified and validated Bcl2-Like 12 (Bcl2L12) as a potent
      glioma oncoprotein with multiple strategic points in apoptosis regulatory
      networks, i.e. effector caspases and the p53 tumor suppressor. Bcl2L12 resides in
      both the cytoplasm and nucleus.  In the cytoplasm, Bcl2L12 functions to inhibit
      caspases 3 and 7, in the nucleus, Bcl2L12 forms a complex with p53, modestly
      reduces p53 protein stability and prevents its binding to selected target gene
      promoter (e.g. p21, DR5, Noxa and PUMA), thereby inhibiting p53-directed
      transcriptomic changes upon DNA damage. Proteomic and multidimensional
      oncogenomic analyses confirmed a Bcl2L12-p53 signaling axis in GBM, as Bcl2L12
      exhibited predominant genomic amplification, elevated mRNA and protein levels in
      GBM tumors with uncompromised p53 function. On the cell biological level, Bcl2L12
      exerts robust inhibition of p53-dependent senescence and apoptosis processes in
      glioma cells. These multi-leveled studies establish Bcl2L12 as an important
      oncoprotein acting at the intersection of nuclear p53 and cytoplasmic caspase
      signaling and point to pharmacological disruption of the Bcl2L12:p53 complex as a
      promising novel therapeutic strategy for the enhanced treatment of GBM.

PMID- 21200142
TI  - An inhibitor of cyclin-dependent kinases suppresses TLR signaling and increases
      the susceptibility of cancer patients to herpesviridae.
AB  - Cyclin-dependent kinase (CDK) inhibitors have been considered as excellent drug
      candidates for cancer therapy owing to their potential capacity to restore cell
      cycle control. The first generation of CDK inhibitors showed modest clinical
      advantages that could be attributed to off-target effects preventing them from
      reaching therapeutic concentrations. A phase I dose-escalation study using the
      second generation multi-CDK inhibitor PHA-793887 was conducted on a total of 19
      patients with advanced refractory malignancies in two sites in Europe: the
      University of Leeds and St. James's Institute of Oncology, Leeds, UK, and the
      Institut Gustave Roussy, Villeujf, France (IGR). Fifteen patients were treated at
      IGR. Six among these patients manifested the reactivation of herpes virus
      replication. In vitro experiments revealed that PHA-793887 severely impaired
      signaling by toll-like receptors (such as TLR3, TLR4 and TLR9) in dendritic cells
      (DC), thus suppressing the production of multiple cytokines (type 1 interferon,
      interleukin-6,-10, -12, and tumor necrosis factoralpha) by mature DC, as well as
      the DC-stimulated production of interferon-gamma by natural killer cells.
      Pharmacological inhibition of glycogen synthase-3beta (GSK-3beta), one of the off
      targets of PHA-793887, did not cause such immunological defects. Altogether,
      these data underscore a hitherto unsuspected immunosuppressive effect of PHA
      793887.

PMID- 21200146
TI  - Refreshed but vulnerable: yeast daughter cells are more sensitive to stress than
      young mothers.

PMID- 21200145
TI  - Function following form: functional differentiation of mammary epithelial cells
      requires laminin-induced polarization of PI3-kinase.

PMID- 21200147
TI  - Phosphorylation of histone H3 in 1- and 2-cell embryos.

PMID- 21200143
TI  - Reviewing once more the c-myc and Ras collaboration: converging at the cyclin D1
      CDK4 complex and challenging basic concepts of cancer biology.
AB  - The c-myc is a proto-oncogene that manifests aberrant expression at high
      frequencies in most types of human cancer. C-myc gene amplifications are often
      observed in various cancers as well. Ample studies have also proved that c-myc
      has a potent oncogenicity, which can be further enhanced by collaborations with
      other oncogenes such as Bcl-2 and activated Ras. Studies on the collaborations of
      c-myc with Ras or other genes in oncogenicity have established several basic
      concepts and have disclosed their underlying mechanisms of tumor biology,
      including "immortalization" and "transformation". In many cases, these
      collaborations may converge at the cyclin D1-CDK4 complex. In the meantime,
      however, many results from studies on the c-myc, Ras and cyclin D1-CDK4 also
      challenge these basic concepts of tumor biology and suggest to us that the
      immortalized status of cells should be emphasized. Stricter criteria and
      definitions for a malignantly transformed status and a benign status of cells in
      culture also need to be established to facilitate our study of the mechanisms for
      tumor formation and to better link up in vitro data with animal results and
      eventually with human cancer pathology.

PMID- 21200148
TI  - Linking Nek6 to p53-induced senescence.

PMID- 21200150
TI  - Aurora kinase roles in idiosyncratic mitoses: the same, but different.

PMID- 21200151
TI  - A role for Nek6 kinase activity in preventing senescence?

PMID- 21200149
TI  - PACSIN 2 represses cellular migration through direct association with cyclin D1
      but not its alternate splice form cyclin D1b.
AB  - Cyclin D1 overexpression is a common feature of many human malignancies. Genomic
      deletion analysis has demonstrated a key role for cyclin D1 in cellular
      proliferation, angiogenesis, and cellular migration. To investigate the
      mechanisms contributing to cyclin D1 functions, we purified cyclin D1a-associated
      complexes by affinity chromatography and identified the PACSIN 2 (protein kinase
      C and casein kinase substrate in neurons 2) protein by mass spectrometry. The
      PACSIN 2, but not the related PACSIN 1 and 3, directly bound wild-type cyclin D1
      (cyclin D1a) at the carboxyl terminus, and failed to bind cyclin D1b, the
      alternative splicing variant of cyclin D1. PACSIN 2 knockdown induced cellular
      migration and reduced cell spreading in LNCaP cells expressing cyclin D1a. In
      cyclin D1(-/-) mouse embryonic fibroblasts (MEFs), cyclin D1a, but not cyclin
      D1b, reduced the cell spreading to a polarized morphology. siPACSIN 2 had no
      effect on cellular migration of cyclin D1(-/-) MEFs. Cyclin D1a restored the
      migratory ability of cyclin D1(-/-) MEFs, which was further enhanced by knocking
      down PACSIN 2 with siRNA. The cyclin D1-associated protein, PACSIN 2, regulates
      cell spreading and migration, which are dependent on cyclin D1 expression.

PMID- 21200153
TI  - Ubiquitin-mediated protein degradation and methylation-induced gene silencing
      cooperate in the inactivation of the INK4/ARF locus in Burkitt lymphoma cell
      lines.
AB  - Burkitt lymphoma is one of the most aggressive tumors affecting humans. Together
      with the characteristic chromosomal translocation that constitutively activates
      the c-Myc oncogene, alterations in cellular tumor suppressor pathways are
      additionally required in order to allow the cells to overcome anti-oncogenic
      barriers and proliferate in an uncontrolled manner. The INK4a/ARF locus on
      chromosome 9p21 is considered a safeguard locus since it encodes the two
      important tumor suppressor proteins, p14(ARF) and p16(INK4a). By regulating the
      p53 and Rb pathways p14(ARF) and p16(INK4a) respectively act as pro-apoptotic and
      cell cycle inhibitor proteins. The importance of the INK4a/ARF locus has been
      well documented in several human tumors as well as in Burkitt lymphoma. Although
      the mechanisms responsible for the transcriptional regulation of the INK4a/ARF
      locus have been thoroughly characterized, less is known about its
      posttranscriptional control. In this study we found that p16(INK4a) and p14(Arf)
      are concurrently inactivated in a panel of BL cell lines. We demonstrate that
      along with the epigenetic silencing of the p16INK4a gene, the complete
      inactivation of the locus is achieved by the improper turnover of INK4/ARF
      proteins by the ubiquitin-proteasome system (UPS), as the proteasome inhibitor MG
      132 blocks p14(ARF) degradation and induces a dramatic stabilization of the
      p16(INK4a) protein. We establish that the simultaneous deregulation of both DNA
      methylation patterns and the ubiquitin-dependent proteolysis system is required
      to completely inactive the INK4/ARF locus, opening new prospects for the
      understanding and treatment of Burkitt lymphoma.

PMID- 21200154
TI  - Deadly triplex: smoke, autophagy and apoptosis.
AB  - Autophagy, a cellular program for organelle and protein turnover, represents
      primarily a cell survival mechanism. However, the role of autophagy in the
      regulation of apoptosis remains unclear. We have observed increases in
      morphological and biochemical indicators of autophagy in human lung from patients
      with chronic obstructive pulmonary disease (COPD). Furthermore, we observed
      induction of autophagic markers in mouse lung subjected to chronic cigarette
      smoke exposure. Recently, we investigated the role of the autophagic protein
      microtubule-associated protein 1 light chain 3B (LC3B) as a regulator of lung
      cell death. We found that LC3B knockout (LC3B(-/-)) mice subjected to chronic
      cigarette smoke exposure have reduced lung apoptosis, and resist airspace
      enlargement, relative to wild-type mice. We therefore examined the mechanisms by
      which LC3B can regulate apoptosis in epithelial cells. We found that LC3B forms a
      complex with the death receptor Fas in lipid rafts of epithelial cells, which
      requires the caveolae-resident protein caveolin-1. Genetic interference of
      caveolin-1 in epithelial cells augments cigarette smoke-induced apoptosis.
      Caveolin-1 knockout mice exhibit increased autophagic markers, apoptosis, and
      airspace enlargement in the lung in response to chronic cigarette smoke. These
      studies demonstrate that LC3B can promote tissue injury during chronic cigarette
      smoke exposure, and suggest a mechanism by which LC3B, through interactions with
      caveolin-1 and Fas, can regulate apoptosis. Targeting the autophagic pathway may
      represent an experimental therapeutic strategy when designing new approaches to
      COPD treatment.

PMID- 21200162
TI  - Emerging issues in sport medicine.

PMID- 21200152
TI  - Temporal changes in Hox gene expression accompany endothelial cell
      differentiation of embryonic stem cells.
AB  - In pluripotent embryonic stem cells (ESCs), expression of the Hox master
      regulatory transcription factors that play essential roles in organogenesis,
      angiogenesis, and maintenance of differentiated tissues, is globally suppressed.
      We investigated whether differentiation of endothelial cells (ECs) from mouse
      ESCs was accompanied by activation of distinct Hox gene expression profiles.
      Differentiation was observed within 3 days, as indicated by the appearance of
      cells expressing specific endothelial marker genes (Flk-1+ /VE-Cadherin+ ).
      Expression of HoxA3 and HoxD3, which drive adult endothelial cell invasion and
      angiogenesis, peaked at day 3 and declined thereafter, whereas expression of
      HoxA5 and HoxD10, which maintain a mature quiescent EC phenotype, was low at day
      3, but increased over time. The temporal and reciprocal changes in HoxD3 and
      HoxA5 expression were accompanied by corresponding changes in expression of
      established downstream target genes including integrin beta3 and Thrombospondin
      2. Our results indicate that differentiation and maturation of ECs derived from
      cultured ESCs mimic changes in Hox gene expression that accompany maturation of
      immature angiogenic endothelium into differentiated quiescent endothelium in
      vivo.

PMID- 21200163
TI  - The future of chronic disease management and the role of sport and exercise
      medicine physicians.

PMID- 21200164
TI  - Sports concussion and the risk of chronic neurological impairment.
AB  - Intense recent media focus on long-term outcomes from sports concussion has
      highlighted concerns on both cognitive deterioration and mental health issues,
      such as depression and suicide. At this time, the scientific evidence to support
      these views is limited, with only a handful of cases thus far reported. Based on
      the literature on this topic that extends back over 50 years, it is clear that
      only a small percentage of athletes suffer such sequelae presumably due to
      recurrent concussive or subconcussive head impacts. At this stage, determining
      which athletes are at future risk is not possible; however, following existing
      concussion guidelines (eg, Zurich guidelines) is likely to be the safest option
      based on current evidence.

PMID- 21200165
TI  - Is there evidence for mandating electrocardiogram as part of the pre
      participation examination?
AB  - The risk of sudden cardiac death may be increased up to 2.8 times in competitive
      athletes compared with nonathletes. The majority of sudden cardiac death cases
      are caused by an underlying abnormality that potentially may be identified on
      cardiovascular screening, depending on the specific abnormality and the content
      of the cardiovascular screening applied. Indeed, today, cardiac screening is
      universally recommended by the cardiac societies [European Society of Cardiology
      (ESC) and American Heart Association (AHA)] and required by the sporting bodies
      [Federation Internationale de Football Association (FIFA) and Union of European
      Football Associations (UEFA)]. Pre-participation examination is by consensus
      understood to include personal history and physical examination; controversy
      exists regarding the usefulness and appropriateness of screening using resting 12
      lead electrocardiogram (ECG), with an apparent transatlantic difference. The ESC
      recommends screening consisting of personal history, physical examination, and 12
      lead resting ECG, whereas recommendations from the AHA includes only personal
      history and physical examination. There is firm scientific ground to state that
      the sensitivity of screening with ECG is vastly superior to, and the cost
      effectiveness significantly better than, screening without ECG. Cardiac screening
      of elite athletes with personal history, physical examination, and ECG is cost
      effective also in comparison with other well-accepted procedures of modern health
      care, such as dialysis and implantable cardiac defibrillators. Newly published
      recommendations for the interpretation of the ECG in athletes (ESC) and future
      studies on ECGs in athletes of different ethnicity, gender, and age may further
      increase the specificity of ECG in cardiac screening, refining the screening
      procedure and lowering the costs for additional follow-up testing. Cardiac
      screening without ECG is not cost-effective and may be only marginally better
      than no screening at all and at a considerable higher cost. The difficulties in
      feasibility and liability issues for recommending ECGs in some countries need to
      be acknowledged but must be dealt with within those countries/systems. On ethical
      grounds, the reasons (logistical, legal, economic) for not screening individual
      athletes should be clearly stated. Alas, the current evidence, as presented here,
      suggests that the ECG should be mandatory in pre-participation screening of
      athletes.

PMID- 21200166
TI  - Is there evidence for recommending electrocardiogram as part of the pre
      participation examination?
AB  - Sudden cardiac death (SCD) is the leading cause of death in young athletes on the
      playing field and typically the result of undiagnosed structural or electrical
      cardiovascular disease. Cardiovascular screening in athletes is routinely
      practiced and endorsed by most major sporting and medical associations, but
      universal agreement on a single screening strategy to identify athletes at risk
      for SCD remains a topic of tremendous debate. The pool of scientific evidence
      supporting the efficacy and cost-effectiveness of electrocardiogram (ECG)
      screening for athletes is growing. However, feasibility and practical concerns
      regarding false-positive results, cost-effectiveness, physician infrastructure,
      and health care resources for large-scale implementation of ECG screening still
      exist. This article examines the evidence related to ECG screening in athletes
      and presents a contemporary model for primary prevention of SCD in sport.

PMID- 21200167
TI  - Return-to-play decisions: are they the team physician's responsibility?
AB  - OBJECTIVE: Return-to-play (RTP) decisions are a central component of the Team
      Physician's clinical work, yet there is little more than anecdotal reference to
      these in the literature. We recently published a 3-step model for return-to-play
      medical decision making and, in the current paper, undertook a systematic review
      of the literature to determine the level of evidence in support of this model.
      DATA SOURCES: PubMed, Web of Science, and CINAHL electronic databases. Any
      article specifically related to concussion, head injuries, neck injuries,
      illness, medical conditions (including cardiovascular and renal), and
      preparticipation in sport or that reported RTP as a clinical outcome was
      excluded. Any article that contained a discussion on one of the components of the
      3-step decision-based RTP model was included. RESULTS: We reviewed 148 articles
      that met the criteria for inclusion and found 98 review articles, 39 original
      articles, 6 case reports, and 5 editorials. Of these, 141 articles mentioned Step
      1 of the medical decision-making process for RTP (Medical Factors), 26 mentioned
      Step 2 (Sport Risk Modifiers), and 20 mentioned Step 3 (Decision Modifiers). Of
      the 148 articles in total, only 13 focused on RTP as the main subject and the
      remaining 135 mentioned RTP anecdotally. Of these 13 articles, 5 were reviews, 4
      were editorials, and 4 were original research. CONCLUSIONS: Although 148 articles
      we retrieved mention RTP in relation to a specific injury, medical condition, or
      specific topic, only 13 articles focused specifically on the RTP decision-making
      process, and 6 of 13 were restricted to Step 1 of the 3-step model (Medical
      Factors). Return-to-play is a fertile field for research and thought leadership
      beginning with a focus on the Team Physician's appropriate role in RTP decision
      making, particularly considering the factors identified in Step 3 (Decision
      Modification).

PMID- 21200168
TI  - Platelet-enriched plasma and muscle strain injuries: challenges imposed by the
      burden of proof.
AB  - OBJECTIVE: To review the evidence for the clinical utilization of autologous
      plasma products in the management of muscle strain injuries. METHOD: Systematic
      review using EMBASE and MEDLINE (up to March 2010). RESULTS: There is no level 1,
      2, and 3 evidence for the use of autologous plasma products in muscle strain
      injuries. Furthermore, significant methodological limitations impact on the
      interpretation of the few published studies in this field. CONCLUSIONS: Although
      basic science and the use of recombinant growth factors in animal models support
      the concept of applying growth factors to acute muscle injuries, it is unclear if
      this evidence can be directly translated to reflect outcomes from platelet
      enriched plasma. There remain a large number of unanswered questions, including
      the principle questions regarding safety and efficacy, which require appropriate
      scientific investigation. It is incumbent on sports physicians wishing to enhance
      athlete care, together with researchers, to search for these answers.

PMID- 21200169
TI  - Platelet-rich plasma treatment for ligament and tendon injuries.
AB  - Platelet-rich plasma (PRP) is derived from centrifuging whole blood, has a
      platelet concentration higher than that of the whole blood, is the cellular
      component of plasma that settles after centrifugation, and contains numerous
      growth factors. There is increasing interest in the sports medicine and athletic
      community about providing endogenous growth factors directly to the injury site,
      using autologous blood products such as PRP, to potentially facilitate healing
      and earlier return to sport after musculoskeletal injury. Despite this interest,
      and apparent widespread use, there is a lack of high-level evidence regarding
      randomized clinical trials assessing the efficacy of PRP in treating ligament and
      tendon injuries. Basic science and animal studies and small case series reports
      on PRP injections for ligament or tendon injuries, but few randomized controlled
      clinical trials have assessed the efficacy of PRP injections and none have
      demonstrated scientific evidence of efficacy. Scientific studies should be
      performed to assess clinical indications, efficacy, and safety of PRP, and this
      will require appropriately powered randomized controlled trials with adequate and
      validated clinical and functional outcome measures and sound statistical
      analysis. Other aspects of PRP use that need to be determined are (1) volume of
      injection/application, (2) most effective preparation, (3) buffering/activation,
      (4) injection technique (1 depot vs multiple depots), (5) timing of injection to
      injury, (6) single application versus series of injections, and (7) the most
      effective rehabilitation protocol to use after PRP injection. With all proposed
      treatments, the doctor and the patient should weigh up potential benefits of
      treatment, potential risks, and costs. Based on the limited publications to date
      and theoretical considerations, the potential risks involved with PRP are
      fortunately very low. However, benefits remain unproven to date, particularly
      when comparing PRP with other injections for ligament and tendon injuries.

PMID- 21200170
TI  - The asthmatic athlete: inhaled Beta-2 agonists, sport performance, and doping.
AB  - The asthmatic athlete has a long history in competitive sport in terms of success
      in performance and issues related to doping. Well documented are detailed
      objective tests used to evaluate the athlete with symptoms of asthma or airway
      hyperresponsiveness and the medical management. Initiated at the 2002 Salt Lake
      City Games, the International Olympic Committee's Independent Asthma Panel
      required testing to justify the use of inhaled beta-2 agonists (IBAs) in Olympic
      athletes and has provided valuable guidelines to the practicing physician. This
      program was educational and documented the variability in prevalence of asthma
      and/or airway hyperresponsiveness and IBA use between different sports and
      different countries. It provided a standard of care for the athlete with
      respiratory symptoms and led to the discovery that asthmatic Olympic athletes
      outperformed their peers at both Summer and Winter Olympic Games from 2002 to
      2010. Changes to the World Anti-Doping Agency's Prohibited List in 2010 permitted
      the use of 2 IBA produced by the same pharmaceutical company. All others remain
      prohibited. However, there is no pharmacological difference between the permitted
      and prohibited IBAs. As a result of these changes, asthmatic athletes are being
      managed differently based on a World Anti-Doping Agency directive that has no
      foundation in pharmacological science or in clinical practice.

PMID- 21200171
TI  - Femoroacetabular impingement: a common cause of hip pain in young adults.
AB  - OBJECTIVE: Femoroacetabular impingement (FAI) is a common cause of hip discomfort
      in young adults. Recently, a better understanding of the pathomechanics and
      morphologic abnormalities in the hip has implicated FAI as a possible factor in
      early osteoarthrosis. The clinical presentation, physical examination findings,
      and radiographic features are discussed in this article. DATA SOURCES: PubMed was
      searched using words and terms including femoacetabular impingement, hip
      osteoarthritis, hip arthroscopy, early osteoarthrosis, and hip dislocation.
      References of relevant studies were searched by hand. STUDY SELECTION: All
      studies directly involving the treatment of FAI were reviewed by 3 authors and
      selected for further analysis, including expert opinion and review articles. DATA
      SYNTHESIS: The quality of each study was assessed, and the results were
      summarized. CONCLUSIONS: Conservative measures, including physical therapy,
      restriction of activities, core strengthening, improvement of sensory-motor, and
      control and nonsteroidal anti-inflammatories are the mainstays of nonsurgical
      treatment. However, surgical management is often necessary to allow full return
      to activity with options including surgical dislocation of the hip, hip
      arthroscopy, periacetabular and rotational osteotomies, and combined hip
      arthroscopy with a limited open exposure. Although the literature is replete with
      short-term evidence to support surgical treatment, there are currently no long
      term prospective data or natural history studies examining the implications of
      FAI and effects of early intervention.

PMID- 21200172
TI  - Office-based ultrasound in sports medicine practice.
AB  - Increasing knowledge, interest, and visibility in the field of sports medicine
      has equipped clinicians in the field with a novel array of diagnostic and
      therapeutic options but has also provided a higher level of complexity in patient
      care. True understanding of the vast spectrum of radiographic technology
      available to the sports clinician has become more critical than ever. Advances
      particularly in the areas of magnetic resonance imaging, diagnostic office
      ultrasound, and 3-dimensional reconstruction computed tomography, as well as
      nuclear medicine, offer the clinician a myriad of diagnostic options in patient
      evaluation. As these advances accumulate, the challenge to optimize care, contain
      cost, and interpret the extensive data generated becomes even more difficult to
      manage. Improving technology, education, and application of office ultrasound
      offers an interesting new tool for the bedside evaluation in real time of dynamic
      motion and pathology of sports-related injuries. As studies continue to validate
      ultrasound's effectiveness in diagnosing injuries to the upper and lower
      extremities compared with more costly magnetic resonance imaging and more
      invasive exploratory surgery, its promise as a cost-effective diagnostic tool is
      growing. A particularly promising development in the care of sports injuries is
      the expansion of injection therapies, and in-office ultrasound provides assurance
      that prolotherapy, platelet-rich plasma, dry needling, corticosteroid, and
      viscosupplementation are delivered accurately and safely. Communication with
      patients continues to increase in complexity because a greater understanding of
      the presence of radiographic abnormalities irrelevant to the current complaint is
      gained. All the accumulated data must then be interpreted and communicated to the
      patient with a firm understanding of not only the patient history and physical
      examination but also the availability, indications, contraindications,
      sensitivity, specificity, and even the cost implications of the spectrum of
      diagnostic options.

PMID- 21200173
TI  - International travel and the elite athlete.
AB  - International travel is a frequent occurrence in the life of the elite athlete;
      such travel can pose challenges to the sport medicine practitioner. Travel is
      also the reality of many recreational level or sub-elite athletes as
      opportunities for international competition and training proliferate. An
      appreciation of the range of responsibilities associated with the preparation for
      and the strategies to facilitate such travel is essential for any physician
      charged with the care of athletes and teams. An appreciation of (1) the medical
      and public health challenges associated with competition in a particular setting;
      (2) the requirements for vaccination and immunization; (3) the strategies for the
      management of jet lag and climatic or environmental extremes; (4) the range of
      supplies and equipment necessary for travel to certain locales; (5) the need to
      ensure the availability of ample familiar and nutritious foods; (6) the potential
      need for specialty care in strange settings; (7) the management of common travel
      associated illness; and (8) the challenges associated with the evacuation of an
      injured athlete are fundamental to the successful management of international
      travel involving athletes and teams. The adoption of a methodical approach to pre
      trip planning can ensure an enhanced travel experience, illness-free training and
      competition, and facilitate optimal performance.

PMID- 21200174
TI  - Public health recommendations for athletes attending sporting events.
AB  - Public health planning in advance of the 2010 Olympic and Paralympic Winter Games
      included an assessment of potential public health risks for athletes attending
      the Games and mitigation activities to reduce those risks, including provision of
      vaccination recommendations to athletes. Physicians providing care to athletes
      who will attend large sporting events at home or abroad should consider their
      need for routine and additional vaccinations well in advance of the event to
      permit completion of vaccination schedules, ensure development of immunity, and
      avoid adverse vaccine reactions in the final stages of athlete training. Specific
      vaccinations recommended will vary depending on the location of the event and
      time of year it is scheduled. Other simple prevention measures for athletes
      include hand washing recommendations, avoiding high-risk foods, practicing safe
      sex, and taking simple precautions to reduce the risk of injuries. No major
      public health problems occurred during the 2010 Winter Games, but a measles
      outbreak began in Vancouver coincident in time with the Games; no known cases
      occurred among participating athletes.

PMID- 21200175
TI  - Midlife physical activity affects successful aging in women.

PMID- 21200176
TI  - Leisure-time physical activity and depression in adolescence.

PMID- 21200177
TI  - Treatment of ACL tears in active young adults.

PMID- 21200178
TI  - Using extracorporeal shock-wave therapy for healing long-bone nonunions.

PMID- 21200179
TI  - Current challenges in the management of the infected patient.
AB  - PURPOSE OF REVIEW: Management of hospital-associated infections (HAIs) has been
      made more challenging by the increasing proportion of immunocompromised or
      otherwise severely ill patients and increasing prevalence of antibiotic-resistant
      pathogens in this environment. This review examines strategies to optimize
      clinical outcomes and lower healthcare costs for patients with HAIs by focusing
      on patient-related, pathogen-related, and drug-related factors. RECENT FINDINGS:
      Factors have converged to increase the risk of infection with antibiotic
      resistant pathogens in the current hospital environment, including the increasing
      prevalence of resistant species and number of hospitalized patients with
      conditions increasingly susceptible to infection with drug-resistant bacteria.
      Although the list of bacterial pathogens associated with HAIs has been fairly
      constant over time, the prevalence and resistance profile of these individual
      species continues to evolve. Periodic antibiograms should be utilized to access
      local patterns of resistance within the different hospital wards. Outcomes for
      patients with HAIs are optimized with early empiric treatment with an appropriate
      regimen, selected on the basis of patient characteristics and local resistance
      patterns. Dosing strategies should be utilized to ensure that the efficacy of an
      appropriate antibiotic is optimized, by achieving the pharmacodynamic target
      predictive of its efficacy. Using these strategies improves quality of care and
      is associated with lower overall healthcare costs. SUMMARY: Bacterial resistance
      is an increasing problem in the hospital environment, and has been associated
      with poorer clinical outcomes and elevated healthcare costs. By using patient
      characteristics, local antibiograms, and dosing strategies to achieve an optimal
      pharmacodynamic profile, early appropriate empiric therapy can be utilized to
      improve clinical outcomes, minimize the development of resistance, and reduce
      healthcare costs.

PMID- 21200180
TI  - Antimicrobial stewardship: bridging the gap between quality care and cost.
AB  - PURPOSE OF REVIEW: Antibiotic resistance continues to rise, whereas development
      of new agents to counter it has slowed. A heightened need exists to maintain the
      effectiveness of currently available agents. This review focuses on the need for
      better antimicrobial stewardship, expected benefits of well designed
      antimicrobial stewardship programs (ASPs), and provides suggestions for
      development of an effective ASP. RECENT FINDINGS: Healthcare-associated
      infections (HAIs) are a significant cause of poor treatment outcomes and elevated
      healthcare and societal costs worldwide. HAIs are often caused by antibiotic
      resistant pathogens; overuse of antibiotics has been linked with antibiotic
      resistance. Benefits of improved antimicrobial stewardship include reduced
      emergence of antibiotic resistance, limitation of drug-related adverse events,
      minimization of other consequences of antibiotic use (e.g., superinfection), and
      reduction of societal and healthcare-related costs. In 2007, the Infectious
      Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of
      America (SHEA) provided guidelines for the development of institutional programs
      to enhance antimicrobial stewardship. Experiences at The Ohio State University
      Medical Center (OSUMC) reinforce this message, while providing specific examples
      of ways to optimize ASP development and implementation. The focus of an ASP
      should be on improving quality of care, reducing drug resistance, and cost
      savings. When implementing an ASP, it is important to identify those most likely
      to resist the ASP, understand their concerns, and develop easy-to-understand
      messages that address these concerns and highlight the benefits of the proposed
      changes. Antibiograms play a key role in identifying local and interdepartmental
      trends in antibiotic susceptibility or resistance. These data are important not
      only in devising best-treatment practices for the institution, but also in
      evaluating the impact of a recently implemented ASP. Other measures of the impact
      of an ASP should include patient outcomes and overall costs or savings. SUMMARY:
      Better antimicrobial stewardship is needed to limit the emergence of antibiotic
      resistance, prolong the effectiveness of currently available agents, improve
      patient outcomes, and reduce healthcare and societal costs associated with HAIs.
      Guidelines from the IDSA/SHEA and experiences at OSUMC provide examples of how
      best to develop an institutional ASP to accomplish these goals.

PMID- 21200181
TI  - Beyond the target pathogen: ecological effects of the hospital formulary.
AB  - PURPOSE OF REVIEW: Antibiotic therapy has the potential for intended as well as
      unintended consequences due to ecological effects that extend beyond the target
      pathogen. This review examines some of the collateral damage and collateral
      benefit that may occur when using antibiotic therapy. RECENT FINDINGS:
      Antibiotics excreted in the gastrointestinal tract cause alterations of the
      indigenous flora. Such disruptions may increase the risk of colonization and
      overgrowth of pathogenic bacteria, including resistant species, with the
      potential for serious infection for an individual patient as well as possible
      hospital-wide dissemination resulting in local outbreaks of infection. For
      example, Clostridium difficile infection (CDI), and particularly associated
      diarrhea and colitis, is a potentially serious and growing problem in hospitals
      worldwide, and is associated with disruption of gut flora through use of broad
      spectrum antibiotics, especially those with antianaerobic activity. Infection
      control measures and improved antibiotic stewardship are key measures for CDI
      prevention. Another example is the risk of intestinal colonization and overgrowth
      with resistant bacteria, which is heightened in surgical patients requiring
      antimicrobial therapy for intraabdominal infections. Results from two Optimizing
      Intra-Abdominal Surgery with Invanz studies (OASIS-I and OASIS-II) suggested
      emergence of resistant Enterobacteriaceae was less likely in these patients
      treated with ertapenem than in those treated with ceftriaxone/metronidazole or
      piperacillin/tazobactam. Finally, recent studies have reported that increased use
      of a nonpseudomonal carbapenem such as ertapenem does not reduce the
      susceptibility of Pseudomonas aeruginosa to pseudomonal carbapenems, for example,
      imipenem or meropenem. In fact, data from one study showed increased
      ertapenem/decreased imipenem use was associated with improved susceptibility of
      P. aeruginosa to imipenem, probably due to decreased selective pressure for
      resistant species. SUMMARY: Improper antibiotic use can be associated with
      detrimental effects related to the ecological impacts of these drugs. Improved
      antibiotic stewardship and appropriate infection control measures are key to
      minimization of the collateral damage associated with antibiotic therapy and may
      even have collateral benefits.

PMID- 21200182
TI  - Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial
      syndrome).
AB  - Chromosome 22q11.2 deletion syndrome is a common syndrome also known as DiGeorge
      syndrome and velocardiofacial syndrome. It occurs in approximately 1:4000 births,
      and the incidence is increasing due to affected parents bearing their own
      affected children. The manifestations of this syndrome cross all medical
      specialties, and care of the children and adults can be complex. Many patients
      have a mild to moderate immune deficiency, and the majority of patients have a
      cardiac anomaly. Additional features include renal anomalies, eye anomalies,
      hypoparathyroidism, skeletal defects, and developmental delay. Each child's needs
      must be tailored to his or her specific medical problems, and as the child
      transitions to adulthood, additional issues will arise. A holistic approach,
      addressing medical and behavioral needs, can be very helpful.

PMID- 21200183
TI  - The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing
      vasculitides based on the French Vasculitis Study Group (FVSG) cohort.
AB  - The 1996 Five-Factor Score (FFS) for systemic necrotizing vasculitides
      (polyarteritis nodosa [PAN], microscopic polyangiitis [MPA], and Churg-Strauss
      syndrome [CSS]) is used to evaluate prognosis at diagnosis. In the current study
      we revisited the FFS, this time including Wegener granulomatosis (WG).We analyzed
      clinical, laboratory, and immunologic manifestations present at diagnosis of
      systemic necrotizing vasculitides for 1108 consecutive patients registered in the
      French Vasculitis Study Group database. All patients met the American College of
      Rheumatology and Chapel Hill nomenclature criteria. Univariable and multivariable
      analyses yielded the 2009 FFS for the 4 systemic necrotizing vasculitides.Overall
      mortality was 19.8% (219/1108); mortality for each of the SNV is listed in
      descending order: MPA (60/218, 27.5%), PAN (86/349, 24.6%), CSS (32/230, 13.9%),
      and WG (41/311, 13.2%) (p < 0.001). The following factors were significantly
      associated with higher 5-year mortality: age >65 years, cardiac symptoms,
      gastrointestinal involvement, and renal insufficiency (stabilized peak creatinine
      >=150 MUmol/L). All were disease-specific (p < 0.001); the presence of each was
      accorded +1 point. Ear, nose, and throat (ENT) symptoms, affecting patients with
      WG and CSS, were associated with a lower relative risk of death, and their
      absence was scored +1 point (p < 0.001). Only renal insufficiency was retained
      (not proteinuria or microscopic hematuria) as impinging on outcome. According to
      the 2009 FFS, 5-year mortality rates for scores of 0, 1, and >=2 were 9%, 21% (p
      < 0.005), and 40% (p < 0.0001), respectively.The revised FFS for the 4 systemic
      necrotizing vasculitides now comprises 4 factors associated with poorer prognosis
      and 1 with better outcome. The retained items demonstrate that visceral
      involvement weighs heavily on outcome. The better WG prognosis for patients with
      ENT manifestations, even for patients with other visceral involvement, compared
      with the prognosis for those without ENT manifestations, probably reflects WG
      phenotype heterogeneity.

PMID- 21200184
TI  - Vasculitis of the gastrointestinal tract in chronic periaortitis.
AB  - The term "chronic periaortitis" (CP), proposed by Mitchinson in 1984, comprises 3
      main entities: idiopathic retroperitoneal fibrosis (IRF), inflammatory abdominal
      aortic aneurysms (IAAAs), and perianeurysmal retroperitoneal fibrosis (PRF).The
      presence of constitutional symptoms, high acute-phase reactants, positive
      autoantibodies, and associated autoimmune diseases suggests a systemic
      inflammatory process. Histopathologic findings show vasculitis with fibrinoid
      necrosis involving the aortic vasa vasorum as well as the small and medium
      retroperitoneal vessels.We reviewed the medical records of 608 patients with a
      diagnosis of vasculitis involving the gastrointestinal (GI) tract at the Mayo
      Clinic between January 1996 and December 2007. Only patients with biopsy-proven
      or typical angiographic findings of vasculitis localized to the GI tract were
      included.Five patients were identified with evidence of CP (1 patient with PRF, 1
      with IRF, and 3 with IAAAs). Three patients were men, and the median age at
      diagnosis was 49 years. The diagnosis of GI vasculitis and CP was made
      simultaneously in 4 patients. At the time of onset, all patients had abdominal
      pain and constitutional manifestations; the median erythrocyte sedimentation rate
      was 62.5 mm/1 h (range, 20-86 mm/1 h). All patients had evidence of mesenteric
      vasculitis at angiography. Three patients also had associated renal artery
      stenoses. Abdominal computed tomography showed spleen infarcts in 2 patients,
      bowel wall thickening in 1, and liver infarction in 1. Two patients underwent
      surgical intervention for acute abdomen; there was histologic evidence of small
      bowel infarcts and infarction of the spleen and liver in 1. Oral prednisone was
      administered to all 5 patients (median starting dose, 60 mg/d; range, 25-80
      mg/d). Three patients also received immunosuppressive agents, 1 tamoxifen, and 1
      anti-tumor necrosis factor therapy. All patients had at least 1 relapse or
      recurrence of vasculitis, but at last visit, GI vasculitis and CP were in
      remission in all 5 patients.This study provides evidence that GI manifestations
      due to mesenteric vasculitis may be associated with CP. Vasculitic involvement of
      the renal arteries is also frequently present in these patients. Aggressive
      immunosuppressive treatment should be promptly initiated to forestall abdominal
      complications. These findings reinforce the hypothesis that a vasculitic process
      plays an important role in the pathogenesis of CP.

PMID- 21200185
TI  - Long-term follow-up of upper and lower extremity vasculitis related to giant cell
      arteritis: a series of 36 patients.
AB  - We conducted this retrospective study to determine the prevalence of giant cell
      arteritis (GCA) in patients exhibiting nonatherosclerotic upper and/or lower
      extremity arterial involvement and to evaluate the clinical features and long
      term outcome of those patients.From January 1997 to March 2008, 36 consecutive
      patients in the Department of Internal Medicine at the University of Rouen
      medical center received a diagnosis of symptomatic upper/lower extremity
      vasculitis related to GCA. In the 36 patients, upper/lower extremity vasculitis
      preceded the initial GCA diagnosis in 7 patients (19.4%), it was identified in
      association with GCA in 13 patients (36.1%), and it developed after the onset of
      GCA in the remaining 16 patients (44.4%). GCA clinical manifestations were severe
      resulting in ischemic complications of the extremities in 10 patients (27.8%).
      GCA-related large-vessel involvement was located in the upper extremity alone in
      21 patients (58.3%), the lower extremity alone in 7 patients (19.4%), and both
      the upper and lower extremities in 8 patients (22.2%).Arterial involvement in GCA
      patients with upper extremity vasculitis was distributed in the subclavian
      (55.6%), axillary (47.2%), and brachial (22.2%) arteries. In patients with lower
      extremity vasculitis, involvement included the internal iliac artery (11.1%),
      common femoral artery (13.9%), superficial femoral artery (33.3%), deep femoral
      artery (5.6%), and popliteal and anterior tibial arteries (5.6%). Aortic
      localizations were common in GCA patients with upper/lower extremity vasculitis
      (68.9% of cases).All patients were given steroid therapy at a median daily dose
      of 1 mg/kg initially. Reconstructive study was performed in 10 patients (27.8%):
      venous bypass graft (n = 6), angioplasty (n = 1), thromboendarteriectomy (n = 2),
      or thrombectomy (n = 1); 2 other patients with extremity ischemia underwent
      amputation. The median observation time was 32 months; the outcome of upper/lower
      extremity vasculitis was disappearance of clinical symptoms (44.4%), improvement
      of clinical manifestations (44.4%), and deterioration of clinical manifestations
      (11.1%). At last follow-up, the median daily dose of prednisone was 6 mg. Steroid
      therapy could be discontinued in 12 patients (33.3%).We found that upper/lower
      extremity vasculitis is not uncommon in patients with GCA, and may be present in
      the early acute phase of GCA. Nevertheless, because upper/lower extremity
      vasculitis occurs during the course of GCA, yearly clinical vascular examinations
      may be adequate to screen for upper/lower extremity vasculitis at an early stage
      in GCA patients. Early diagnosis of GCA-related upper/lower extremity vasculitis
      is crucial, and can result in decreased severe ischemic complications. Because
      aortic localizations were common, GCA patients with upper/lower extremity
      vasculitis should undergo routine investigations for underlying life-threatening
      aortic complications (aortic ectasia/aneurysm). We also suggest that patients
      exhibiting aortic complications should undergo routine clinical vascular
      examination to detect upper/lower extremity vasculitis.

PMID- 21200186
TI  - Osseous manifestations of adult Gaucher disease in the era of enzyme replacement
      therapy.
AB  - Enzyme replacement therapy (ERT) for Gaucher disease with mannose-terminated
      glucocerebrosidase has proved its therapeutic position with salutary effects on
      hematologic abnormalities, visceral infiltration, and quality of life. The
      frequency of new bone complications is reduced but not eliminated. Established
      osteonecrosis is beyond salvage. A systematic description of the burden of bone
      manifestations, persisting despite ERT, should inform future remedial strategies.
      Thus, we conducted this study to quantify the burden of residual skeletal disease
      and to explore putative relationships between clinical, radiologic, and
      biochemical factors and bone sequelae associated with disability.Consecutive
      adult patients attending 3 referral centers in the United Kingdom were invited to
      participate. A representative group of 100 patients agreed to a structured
      interview, clinical examination, radiologic review, and completion of
      questionnaires. Osteonecrosis was evident in 43%, Erlenmeyer flask deformity in
      59%, fragility fracture in 28%, osteomyelitis in 6%, and lytic lesions in 4%.
      Mobility was impaired in 32% of patients, while 15% experienced significant pain.
      The EuroQol 5D (EQ5D) quality of life summary measure was reduced and was
      associated with osteonecrosis and fragility fracture. Eight patients experienced
      new osteonecrosis after the start of ERT, though the presentation and evolution
      were often atypical. Nine patients had been treated from childhood and had an
      excellent outcome. Osteonecrosis was associated with age of presentation and with
      splenectomy-indeed, we observed a strong temporal association between splenectomy
      and incidence of osteonecrosis.The biomarkers PARC/CCL18 and chitotriosidase were
      associated with prevalent osteonecrosis, and, in particular, with osteonecrosis
      occurring despite treatment. This study documents significant residual skeletal
      pathology and disability in patients in the mature phase of their treatment in a
      developed region. The temporal association between splenectomy and osteonecrosis
      implies causation. The relationship between clinical and biochemical markers and
      existing bone complications sets the scene for future prospective studies that
      will focus on management strategies informed by credible assessment of risk.

PMID- 21200187
TI  - Histoplasmosis in Australia: report of 16 cases and literature review.
AB  - We describe 16 previously unreported patients with histoplasmosis from Queensland
      and northern New South Wales, Australia, and review all previous Australian
      reports, providing 63 cases in total to study (17 cases of acute pulmonary
      histoplasmosis, 2 cases of chronic pulmonary disease, and 44 cases of systemic
      disease, including 17 cases of single-organ infection and 27 instances of
      disseminated disease). All acute pulmonary disease was acquired in Australia,
      with 52% of systemic disease definitely autochthonous. Most cases of single-organ
      disease occurred in immunocompetent patients (76%), and were oropharyngeal (53%)
      in location. Forty-one percent of disseminated disease occurred in patients with
      human immunodeficiency virus (HIV). Patients with HIV had high rates of systemic
      symptoms, pancytopenia, fungemia, and hepatosplenomegaly. Oropharyngeal and
      adrenal involvement as well as systemic symptoms were prominent in
      immunocompetent patients with disseminated disease, with 6 of 7 cases of adrenal
      involvement leading to Addison disease. Most systemic disease was diagnosed by
      culture of Histoplasma capsulatum. Where serology was assessed in cases other
      than acute pulmonary disease, it was positive in only 32%.Prognosis for patients
      with single-organ disease was excellent. Disseminated disease was associated with
      recurrence in 30% and death in 37%. The results of this study confirm several
      previously known patterns of disease but also provide new insights into this rare
      but endemic condition in Australia.

PMID- 21200189
TI  - Neurocysticercosis in Houston, Texas: an update.
AB  - Neurocysticercosis, one of the most common parasitic infections of the human
      nervous system, has emerged as an important infection in the United States.
      Neurocysticercosis causes significant morbidity associated with acute seizures,
      chronic epilepsy, and hydrocephalus.We retrospectively identified patients with
      definitive or probable neurocysticercosis seen at Ben Taub General Hospital, the
      largest public teaching hospital in Houston, Texas, from September 1997 through
      December 2005. We collected demographic, clinical, therapeutic, and outcome
      variables. Neurocysticercosis was classified according to the location of cysts
      in imaging studies. We compared cases with parenchymal and extraparenchymal
      disease.We included 111 patients (48 had definitive and 63 probable
      neurocysticercosis). The mean age was 28.6 years (standard deviation, 13.6 yr),
      and the male to female ratio was 2:1. Most patients (93%) were Hispanic
      immigrants. Sixty (54%) patients had parenchymal disease, 22 (20%)
      intraventricular, 13 (12%) subarachnoid disease, and 13 (12%) had calcifications
      only. Additionally, 2 patients had hydrocephalus only, and 1 had ocular
      cysticercosis. Thirteen (40%) of 32 patients with parenchymal disease and 3 (30%)
      of 10 patients with calcifications had relapsed seizures at follow-up.
      Extraparenchymal disease was associated with longer duration of hospitalization
      compared with parenchymal disease. No deaths were identified in our series during
      a median follow-up of 1 year.Neurocysticercosis has emerged as an important
      parasitic infection in developed countries as a result of increased migration.
      With current management, mortality is limited, but there continues to be
      significant morbidity. Further studies of the epidemiology and pathophysiology of
      the infection are urgently needed to develop better preventive and therapeutic
      strategies.

PMID- 21200190
TI  - Coccidioidal meningitis: disseminated disease in patients without HIV/AIDS.

PMID- 21200188
TI  - Fusarium infection in lung transplant patients: report of 6 cases and review of
      the literature.
AB  - Fusarium is a fungal pathogen of immunosuppressed lung transplant patients
      associated with a high mortality in those with severe and persistent neutropenia.
      The principle portal of entry for Fusarium species is the airways, and lung
      involvement almost always occurs among lung transplant patients with disseminated
      infection. In these patients, the immunoprotective mechanisms of the transplanted
      lungs are impaired, and they are, therefore, more vulnerable to Fusarium
      infection. As a result, fusariosis occurs in up to 32% of lung transplant
      patients. We studied fusariosis in 6 patients following lung transplantation who
      were treated at Massachusetts General Hospital during an 8-year period and
      reviewed 3 published cases in the literature. Cases were identified by the
      microbiology laboratory and through discharge summaries. Patients presented with
      dyspnea, fever, nonproductive cough, hemoptysis, and headache. Blood tests showed
      elevated white blood cell counts with granulocytosis and elevated inflammatory
      markers. Cultures of Fusarium were isolated from bronchoalveolar lavage, blood,
      and sputum specimens.Treatments included amphotericin B, liposomal amphotericin
      B, caspofungin, voriconazole, and posaconazole, either alone or in combination.
      Lung involvement occurred in all patients with disseminated disease and it was
      associated with a poor outcome. The mortality rate in this group of patients was
      high (67%), and of those who survived, 1 patient was treated with a combination
      of amphotericin B and voriconazole, 1 patient with amphotericin B, and 1 patient
      with posaconazole. Recommended empirical treatment includes voriconazole,
      amphotericin B or liposomal amphotericin B first-line, and posaconazole for
      refractory disease. High-dose amphotericin B is recommended for treatment of most
      cases of fusariosis. The echinocandins (for example, caspofungin, micafungin,
      anidulafungin) are generally avoided because Fusarium species have intrinsic
      resistance to them. Treatment should ideally be based on the Fusarium isolate,
      susceptibility testing, and host-specific factors. Prognosis of fusariosis in the
      immunocompromised is directly related to a patient's immune status. Prevention of
      Fusarium infection is recommended with aerosolized amphotericin B deoxycholate,
      which also has activity against other important fungi.

PMID- 21200191
TI  - A desmoid tumor associated with a ruptured silicone breast implant.

PMID- 21200192
TI  - Skin grafts and local flaps.
AB  - Expedited healing of skin wounds is essential regardless of surgical specialty.
      Any skin deficiency will thwart this basic intent, and an alternative must be
      sought. The autogenous skin graft or local flap has long had a major role in
      satisfying this objective. Various forms of autogenous skin grafts are to be
      differentiated from local flaps, primarily on the basis of vascularization. The
      indications for either, their surgical anatomy, harvest techniques, and
      limitations, including pitfalls, need to be outlined. Skin grafts are the
      simplest means to restore skin integrity. If skin grafts are contraindicated, a
      flap may be essential. For this purpose, the "top ten" local "workhorse" flaps
      are briefly described in this article. Accompanying videos further elaborate the
      requisite surgical anatomy and harvest techniques. As a problem-solving
      specialty, it is incumbent upon us to first prevent, then be able to provide
      rapid, efficient, and efficacious healing of, any surgical wound, iatrogenic or
      otherwise. Skin grafts and local flaps are fundamental elements for achieving
      this goal when healing by primary or secondary intent is not possible. Whether
      one is a "reconstructive" or "aesthetic" plastic surgeon, knowledge of these
      basic tenets will ensure maintenance of competency.

PMID- 21200193
TI  - Discussion. Breast cancer incidence in adolescent males undergoing subcutaneous
      mastectomy for gynecomastia: is pathologic examination justified? A retrospective
      and literature review.

PMID- 21200194
TI  - Quality of life of patients who undergo breast reconstruction after mastectomy:
      effects of personality characteristics.
AB  - BACKGROUND: Reconstruction after mastectomy has become an integral part of breast
      cancer treatment. The effects of psychological factors on quality of life after
      reconstruction have been poorly investigated. The authors examined clinical and
      personality characteristics related to quality of life in patients receiving
      reconstructive surgery. METHODS: All patients received immediate reconstruction
      and were evaluated in the week before tissue expander implantation (T0) with a
      semistructured interview for demographic and clinical characteristics, the
      Temperament and Character Inventory, the Inventory of Interpersonal Problems, the
      Short Form Health Survey, the Severity Item of the Clinical Global Impression,
      the Hamilton Depression Rating Scale, and the Hamilton Anxiety Rating Scale.
      Assessment with the Short Form was repeated 3 months after expander placement
      (T1). Statistics were calculated with univariate regression and analysis of
      variance. Significant variables were included in a multiple regression analysis
      to identify factors related to the change T1-T0 of the mean of the Short Form
      transformed scores. Results were significant when p was less than or equal to
      0.05. RESULTS: Fifty-seven women were enrolled. Results of multiple regression
      analysis showed that the Temperament and Character Inventory personality
      dimension harm avoidance and the Inventory of Interpersonal Problems domain
      vindictive/self-centered were significantly and independently related to the
      change in Short Form mean score. CONCLUSIONS: Personality dimensions and patterns
      of interpersonal functioning produce significant effects on patients' quality of
      life during breast reconstruction. Patients with high harm avoidance are
      apprehensive and doubtful. Restoration of body image could help them to reduce
      social anxiety and insecurity. Vindictive/self-centered patients are resentful
      and aggressive. Breast reconstruction could symbolize the conclusion of a
      reparative process and fulfill the desire of revenge on cancer.

PMID- 21200195
TI  - Are patients making high-quality decisions about breast reconstruction after
      mastectomy? [outcomes article].
AB  - BACKGROUND: Variation in rates of breast reconstruction after mastectomy has
      raised concerns about the quality of decisions about reconstruction. The authors
      sought to evaluate patient decision making about reconstruction, using a
      validated measure of knowledge and preferences related to reconstruction.
      METHODS: A cross-sectional survey of early-stage breast cancer survivors from
      four university medical centers was conducted. The survey included measures of
      knowledge about specific reconstruction facts, personal goals and concerns, and
      involvement in decision making. A multivariable linear regression model of
      characteristics associated with knowledge and a logistic regression model of
      factors associated with having reconstruction were developed. RESULTS: A total of
      84 patients participated (59 percent response rate). Participants answered 37.9
      percent of knowledge questions correctly. Higher education (beta, 15 percent; p =
      0.003) and having reconstruction (beta, 21 percent; p < 0.0001) were associated
      with higher knowledge. The goals "use your own tissue to make a breast" (odds
      ratio, 1.53; 95 percent CI, 1.15, 2.05) and "wake up after mastectomy with
      reconstruction underway" (odds ratio, 1.66; 95 percent CI, 1.30, 2.12) were
      associated with reconstruction. The goal "avoid putting foreign material in your
      body" was associated with no reconstruction (odds ratio, 0.64; 95 percent CI,
      0.48, 0.86). Most patients reported they mainly made the decision or made the
      decision with the doctor equally (93 percent; 95 percent CI, 85 to 97 percent)
      and that their degree of involvement was about right (85 percent; 95 percent CI,
      75 to 91 percent). CONCLUSIONS: Women treated with mastectomy in this study were
      not well-informed about breast reconstruction. Treatments were associated with
      patients' goals and concerns, however, and patients were highly involved in their
      decisions. Knowledge deficits suggest that breast cancer patients would benefit
      from interventions to support their decision making.

PMID- 21200196
TI  - Is oncologic safety compatible with a predictably viable mastectomy skin flap?
AB  - BACKGROUND: Necrosis with partial loss of mastectomy flaps is an all-too-common
      complication of otherwise advantageous skin-sparing mastectomies. Central to the
      problem of predictable flap viability is the thickness of the skin flaps. Seeking
      a balance between the preservation of adequate flap thickness and maintenance of
      oncologic principles, the authors sought guidelines to help the oncologic surgeon
      identify the non-breast-bearing subcutaneous layer of tissue between the
      epithelial/dermal tissue of the breast and its parenchyma. METHODS: Breast
      specimens of women receiving reduction mammaplasty were prospectively examined by
      an experienced, blinded breast pathologist. Subcutaneous tissue thickness was
      measured from caudal dermis to breast parenchyma and correlated with age, body
      mass index, and breast specimen weight. RESULTS: No significant correlation was
      found between body mass index, age, or breast sample weight and the thickness of
      the subcutaneous tissue. Measurements did reveal a consistent and distinct layer
      of non-breast-bearing subcutaneous tissue between the dermis and the breast
      parenchyma, with a median thickness of about 1 cm. CONCLUSION: Both oncologic
      safety and a viable skin flap can be achieved if the subcutaneous layer present
      in most breasts is used as a guide for elevating the skin flaps, with subsequent
      oncologically safe resection of the cancer-containing breast parenchyma.

PMID- 21200197
TI  - Internal mammary intercostal perforators instead of the true internal mammary
      vessels as the recipient vessels for breast reconstruction.
AB  - BACKGROUND: Free tissue transfer has become a mainstay in breast reconstruction,
      with the internal mammary system frequently used as the recipient vessels.
      Sacrificing the internal mammary artery, however, eliminates the potential to use
      this vessel as a coronary artery bypass conduit in the future and potentially
      increases recipient-site morbidity. The authors' goal was to evaluate the
      learning curve and effectiveness of their use of the internal mammary intercostal
      perforators for microsurgical breast reconstruction. METHODS: The authors
      reviewed one surgeon's consecutive series of 100 abdominal adipocutaneous
      perforator flap breast reconstructions (72 patients) from July of 2005 through
      January of 2007. The internal mammary perforators were used as recipient vessels
      in 23 flaps, the traditional internal mammary vessels were used in 66, and the
      thoracodorsal vessels were used in 11. To see if there was a learning curve,
      flaps were analyzed in five consecutive cohorts of 20. RESULTS: A learning curve
      was shown: internal mammary perforators were used in 5 percent of the first
      cohort and 45 percent of flaps in the final cohort. Flap survival was 99 percent;
      the one failure occurred in a traditional internal mammary flap reconstruction.
      Small palpable areas of fat necrosis were observed in one internal mammary
      perforator flap (4.3 percent) and in five traditional internal mammary or
      thoracodorsal flaps (6.5 percent). CONCLUSIONS: In all the authors' cohorts,
      internal mammary perforator vessels were used safely without increasing the
      incidence of flap failure or fat necrosis seen with the traditional approach. The
      learning curve for this technique resulted in increased use of these internal
      mammary perforators, indicating that operator experience is critical.

PMID- 21200198
TI  - Chronic postoperative breast pain: danger zones for nerve injuries.
AB  - BACKGROUND: Postoperative breast pain is a frequent complaint, reported by 50
      percent of women following a breast procedure. Breast pain interferes with sexual
      activity, as reported by 48 percent of patients, exercise (36 percent), social
      activity (13 percent), and employment (6 percent). METHODS: To define neurogenic
      causes of chronic postoperative breast pain, the authors performed a
      retrospective review of consecutive patients from a single surgeon and performed
      10 anatomical bilateral dissections. The authors evaluated the most commonly
      injured nerves, based on zone of injury, injury type, and precedent breast
      procedure. Dissections referenced the zone of injury with the specific procedure
      and designated the individual nerves at risk. RESULTS: The authors identified 57
      patients with chronic breast pain from breast reconstruction (n = 38), reduction
      (n = 2), mastopexy (n = 2), augmentation (n = 4) and irradiation (n = 11). On the
      basis of anatomic innervation, the authors designated five zones of nerve injury:
      superior, medial, inferior, lateral, and central/nipple-areola complex. The
      lateral zone was most commonly injured (79 percent), followed by inferior (10.5
      percent), medial (5 percent), central (3.5 percent), and superior (2 percent)
      zones. Forty-two patients suffered intercostal nerve neuromas from mechanical
      nerve trauma/entrapment, with pain at the surgical scar or nearby tissue
      dissection. Four patients with traction-stretch neuropathy had pain from blunt
      augmentation pocket dissection. Eleven patients with irradiation-induced
      neuropathy had diffuse, nonlocalized nerve pain. CONCLUSIONS: By shifting the
      approach to chronic breast pain from "global chronic breast pain" to defined
      danger zones of nerve injury, the practitioner can identify the type of nerve
      injury and associate the most common nerve injury to a given breast procedure.
      This approach should assist in diagnosis and treatment, and ultimately improve
      patient morbidity.

PMID- 21200199
TI  - Rupture rate and patterns of shell failure with the McGhan Style 153 double-lumen
      breast implant.
AB  - BACKGROUND: In 2005, the McGhan Style 153 double-lumen breast implant was removed
      from the market secondary to a higher rupture rate when contrasted with other
      implants in the Core Study group. The high rupture rate was attributed to the
      development of a posterior tear in the shell where the inner implant is bonded to
      the posterior wall of the device. The purpose of this study was to report the
      existing rupture rate and describe the apparent mechanism of failure in the Style
      153 double-lumen breast implant. METHODS: Ninety-seven patients (157 implants)
      who received the McGhan Style 153 double-lumen breast implant by the senior
      author were reviewed. Intraoperative observations and photographic images of
      ruptured implants were reviewed and characterized based on severity and location
      of implant rupture. RESULTS: With a mean length of follow-up of greater than 6
      years (82 months), the rupture rate was 19.1 percent per implant. Physical
      examination (60 percent) was the most common method of rupture detection.
      Ruptures tended to occur in the marginal aspect (63 percent) of the implant. Only
      three ruptures occurred secondary to a disruption of the inner bladder from the
      posterior portion of the implant. CONCLUSIONS: The rupture rate of the Style 153
      double-lumen breast implant is higher than previously thought, with a rate of
      19.1 percent. A majority of ruptures occurred in the peripheral aspects of the
      implant. It is postulated that these ruptures were likely secondary to fold flaws
      that led to failure of the implant shell.

PMID- 21200200
TI  - Discussion. Rupture rate and patterns of shell failure with the McGhan Style 153
      double-lumen breast implant.

PMID- 21200201
TI  - Breast implant complication review: double capsules and late seromas.
AB  - BACKGROUND: The problem of double capsules and late seromas is a relatively new
      phenomenon in breast augmentation surgery. METHODS: The author's experience with
      double capsules in 14 patients is outlined. The author reviewed all primary
      bilateral breast augmentations and primary bilateral mastopexy-augmentations
      after the moratorium in 1992. There were 209 patients with saline implants, 160
      patients with CML and CMH Microcell textured surface implants, 105 patients with
      Biocell textured surface silicone gel breast implants, and 152 patients with
      smooth round silicone gel breast implants. Complications and revisions were
      reviewed to see if any patterns emerged. RESULTS: Fourteen patients were found to
      have double capsules. Double capsules were only seen with the Biocell textured
      surface implant. Three patients developed late seromas (more than a year after
      their original surgery), with two patients requiring urgent drainage of an
      expanding seroma/hematoma. Seven patients were found to have double capsules as
      an incidental finding for procedures, such as asymmetry and bottoming out, and
      five patients were found to have double capsules when surgery was performed for
      capsular contracture. The review of complications and revisions showed that the
      silicone gel implants were far better than saline implants. Highly cohesive
      Microcell textured CMH and CML implants had by far the best capsular contracture
      profile. Biocell texturing increased the capsular contracture rate. CONCLUSIONS:
      Double capsules and late seromas are a relatively new problem in breast
      augmentation surgery. The problem was not seen in smooth saline or smooth
      silicone gel breast implants but only in aggressively textured implants.

PMID- 21200202
TI  - Mesenchymal stem cell-induced cranial suture-like gap in rats.
AB  - BACKGROUND: Mesenchymal stem cells are used in the reconstruction of many organs
      and tissues. However, there are no data regarding cranial suture regeneration
      using mesenchymal stem cells. Because cranial sutures are important for cranial
      bone growth, the authors examined whether mesenchymal stem cells could aid with
      suture reformation in adolescent rats. METHODS: Mesenchymal stem cells were
      isolated from bone marrow of rat femora. Twenty 4-week-old Fischer 344 male rats
      received sagittal suture and bone defects with a diameter of 6.0 mm, and
      mesenchymal stem cells were grafted with membranes. Twenty control rats underwent
      empty membrane transplantation. The mesenchymal stem cell and control groups were
      killed at 4, 8, 16, and 24 weeks after surgery. The parietal bones, including the
      sagittal suture, were observed under a light microscope. Bone structures were
      measured on digitized photomicrographs captured in a computer. For each sample,
      bone and suture regeneration were observed by dorsoventral cephalograms. RESULTS:
      In 4- and 8-week control and mesenchymal stem cell groups, a small volume of new
      bone formation was observed. In the 16- and 24-week mesenchymal stem cell groups,
      a large amount of new bone formation and a suture-like gap were identified. In
      contrast, only a small volume of new bone formation along with craniosynostosis
      was detected in the 24-week control group. CONCLUSION: These results suggest that
      mesenchymal stem cell grafting may be a novel option for cranioplasty, not only
      repairing bone tissue but also resulting in suture-like gap formation, which may
      advance cranial bone growth.

PMID- 21200203
TI  - Luminescence imaging of regenerating free bone graft in rats.
AB  - BACKGROUND: Bone transplantation is an important procedure often used for bone
      defect reconstruction after trauma and malignancies. However, the kinetics of
      free bone graft-derived cells remains unclarified. The authors examined the
      kinetics of graft-derived cells using transgenic rats systemically expressing
      firefly luciferase. METHODS: Free iliac bone grafts (5 * 5 * 2 mm, n = 10)
      derived from luciferase transgenic rats were transplanted into the subcutaneous
      space of the back of wild-type Lewis rats, and the kinetics of graft-derived
      cells were evaluated over time by determining the level of luminescence emission.
      RESULTS: Although the luminescence level emitted by luciferase decreased after
      transplantation, a substantial luminescence level (mean, 1.6 * 10(7)
      photons/second) was emitted from donor-derived cells even at 180 days after
      transplantation, suggesting a long-term survival of graft-derived cells. In a
      computed tomographic image analysis of bone grafts retrieved 180 days after
      transplantation, high-luminescence grafts with a sufficient number of viable
      graft-derived cells (mean, 2.6 * 10(7) photons/second; n = 4) showed
      significantly higher bone graft volume (3.1-fold) and polar moment of inertia of
      area (7.2-fold) than low-luminescence grafts (mean, 1.0 * 10(7) photons/second; n
      = 4), indicating that high-luminescence grafts maintain better conditions.
      CONCLUSION: These results suggest that bone graft-derived cells can survive for a
      long time and that the presence of a sufficient number of viable graft-derived
      cells is essential for graft engraftment and remodeling.

PMID- 21200204
TI  - Bone morphogenetic protein-2 retained in synthetic polymer/beta-tricalcium
      phosphate composite promotes hypertrophy of a vascularized long bone graft in
      rabbits.
AB  - BACKGROUND: Vascularized bone grafting is a useful method for repairing critical
      bone defects. The repaired bone often presents compromised mechanical strength
      because of insufficient thickness of the graft. To promote the hypertrophic
      response, bone morphogenetic protein (BMP) with osteoinductive capacity may be
      effective. This study was designed to evaluate the efficacy of BMP in rabbits.
      METHODS: The first metatarsal bones with or without feeding vessels were
      transferred to critical-sized bone defects in the femurs of rabbits. Recombinant
      human (rh) BMP-2 (0, 30, or 60 MUg) with a carrier material composed of 30 mg of
      beta-tricalcium phosphate powder, 30 mg of a polymer gel (p
      dioxanone/polyethylene glycol block copolymer) was placed in contact with the
      cortical surface and the elevated periosteum of the vascularized bone graft.
      After surgery, hypertrophic changes were evaluated radiographically. Twelve weeks
      after surgery, the reconstructed femurs were harvested for investigation by
      biomechanical and histologic methods. RESULTS: Rapid hypertrophy was observed on
      radiographs in the vascularized bone grafts with rhBMP-2-retaining implants. The
      increase of bone volume and the biomechanical strength were dependent on the dose
      of rhBMP-2 (p < 0.01). Histologic sections in the vascularized bone grafts with
      rhBMP-2-retaining implants revealed a large amount of newly formed bone.
      CONCLUSION: The potential use of BMP may improve clinical outcome by promoting
      hypertrophy of the vascularized bone graft and shortening the treatment time.

PMID- 21200205
TI  - Assessment of biphasic calcium phosphate to repair nasal septum defects in sheep.
AB  - BACKGROUND: Saddle nose and septal perforations are among the most surgically
      challenging situations in nasal reconstruction. They require a significant volume
      of autologous graft and a complex surgical procedure. The aim of this study was
      to evaluate the biocompatibility of the biphasic calcium phosphate implant in the
      nasal septum and its ability to replace septal skeleton with unilateral or
      bilateral exposure. METHODS: Thirty sheep underwent anterior nasal septum
      perforation. Only 20 septa were repaired with the implant exposed to nasal
      content on bilateral (group 2) and unilateral (group 3) sides. After 45 days of
      spontaneous cicatrization, the surface of new airway mucosa covering implants and
      the amount of closure were evaluated macroscopically. Light microscopy,
      histomorphometry, immunohistochemistry, and transmission electron microscopy were
      performed to assess soft-tissue growth and differentiation. Statistical analysis
      was performed by means of the Mann-Whitney test. RESULTS: The mean rate of
      mucoperichondrial flap recovery of the implant was 66 percent in group 2 and 82
      percent in group 3, and was significantly different from that of the control
      group (p < 10(-4)). The mean amount of closure was 32 and 64 percent,
      respectively (p < 10(-3)). The thickness of the perichondrium was greater than
      the control on both sides (p < 10(-4)). Vascularized soft tissues and bone
      formation invaded pores of implants. No pathologic inflammation was observed in
      submucosa. Moderately differentiated and well differentiated newly formed
      epithelium were the most frequent types observed, with good correlation between
      immunostaining and morphologic features. CONCLUSION: These data suggest a good
      biocompatibility of biphasic calcium phosphate and its ability to repair the
      nasal septum in sheep.

PMID- 21200207
TI  - The reconstruction of male hair-bearing facial regions.
AB  - BACKGROUND: Loss of hair-bearing regions of the face caused by trauma, tumor
      resection, or burn presents a difficult reconstructive task for plastic surgeons.
      The ideal tissue substitute should have the same characteristics as the facial
      area affected, consisting of thin, pliable tissue with a similar color match and
      hair-bearing quality. METHODS: This is a retrospective study of 34 male patients
      who underwent reconstruction of hair-bearing facial regions performed by the
      senior author (J.J.P.). Local and pedicled flaps were used primarily to
      reconstruct defects after tumor extirpation, trauma, infections, and burns. Two
      patients had irradiation before reconstruction. Two patients had prior facial
      reconstruction with free flaps. RESULTS: The authors found that certain
      techniques of reconstructing defects in hair-bearing facial regions were more
      successful than others in particular facial regions and in different sizes of
      defects. CONCLUSION: The authors were able to develop a simple algorithm for
      management of facial defects involving the hair-bearing regions of the eyebrow,
      sideburn, beard, and mustache that may prospectively aid the planning of
      reconstructive strategy in these cases.

PMID- 21200206
TI  - Postoperative quantitative assessment of reconstructive tissue status in a
      cutaneous flap model using spatial frequency domain imaging.
AB  - BACKGROUND: The purpose of this study was to investigate the capabilities of a
      novel optical wide-field imaging technology known as spatial frequency domain
      imaging to quantitatively assess reconstructive tissue status. METHODS: Twenty
      two cutaneous pedicle flaps were created on 11 rats based on the inferior
      epigastric vessels. After baseline measurement, all flaps underwent vascular
      ischemia, induced by clamping the supporting vessels for 2 hours (either
      arteriovenous or selective venous occlusions); normal saline was injected into
      the control flap and hypertonic-hyperoncotic saline solution was injected into
      the experimental flap. Flaps were monitored for 2 hours after reperfusion. The
      spatial frequency domain imaging system was used for quantitative assessment of
      flap status over the duration of the experiment. RESULTS: All flaps demonstrated
      a significant decline in oxyhemoglobin and tissue oxygen saturation in response
      to occlusion. Total hemoglobin and deoxyhemoglobin were increased markedly in the
      selective venous occlusion group. After reperfusion and the administration of
      solutions, oxyhemoglobin and tissue oxygen saturation in those flaps that
      survived gradually returned to baseline levels. However, flaps for which
      oxyhemoglobin and tissue oxygen saturation did not show any signs of recovery
      appeared to be compromised and eventually became necrotic within 24 to 48 hours
      in both occlusion groups. CONCLUSIONS: Spatial frequency domain imaging
      technology provides a quantitative, objective method of assessing tissue status.
      This study demonstrates the potential of this optical technology to assess tissue
      perfusion in a very precise and quantitative way, enabling wide-field
      visualization of physiologic parameters. The results of this study suggest that
      spatial frequency domain imaging may provide a means for prospectively
      identifying dysfunctional flaps well in advance of failure.

PMID- 21200208
TI  - The rationale for direct linear closure of facial Mohs' defects.
AB  - BACKGROUND: Closing Mohs' defects is a challenging undertaking for surgeons.
      There are many methods, including linear repair, local flaps, and skin grafts.
      Traditionally, geometric flaps have been a mainstay, particularly in the cheek
      and forehead. However, many flaps violate basic principles of following relaxed
      skin tension lines; also, they often necessitate significant dissection. METHODS:
      All repairs of Mohs' facial defects performed sequentially from 2001 to 2008 by
      the senior author (J.F.T.) were reviewed. Chart review identified the size and
      location of the defect, method of closure, and complications. RESULTS: Chart
      review revealed 1354 reconstructions, with 475 direct repairs (35 percent). The
      highest rate of direct repair was seen in the forehead (77 percent). The lowest
      rate of direct repair was seen in the nose (7 percent). Analysis of cases
      revealed good results, with very low morbidity for direct linear closure.
      CONCLUSIONS: For many large defects, the simple method of direct linear closure
      often yields results superior to those of more time-consuming local flap options.
      Several dogmas of facial reconstruction are too unyielding, and the option of
      direct repair should not be overlooked. Traditional estimates of defect size
      requiring flap repair are incorrect; it is possible to close some large defects
      by direct approximation, with superior results.

PMID- 21200209
TI  - Reconstruction of high maxillectomy defects with the fibula osteomyocutaneous
      flap in combination with titanium mesh or a zygomatic implant.
AB  - BACKGROUND: This retrospective review examined the authors' patients who
      underwent reconstruction of high maxillectomy defects with fibula
      osteomyocutaneous flaps in combination with titanium mesh or a zygomatic implant.
      Outcome assessments included aesthetic, speech, and masticatory function.
      METHODS: Twenty patients who underwent reconstruction of high maxillectomy
      defects with fibula osteomyocutaneous flaps in combination with titanium mesh (n
      = 19) or a zygomatic implant (n = 1) were reviewed. The fibula was fashioned to
      recreate the alveolar ridge and pterygomaxillary buttress, and the skin paddle
      was applied to restore the palate and nasal airway. The anterior wall of the
      maxilla and the orbital floor were reconstructed with titanium mesh in 19
      patients. In four patients with extensive soft-tissue defects, a radial forearm
      flap was combined to restore missing soft tissue. Aesthetics, speech, and
      masticatory function were evaluated postoperatively. RESULTS: Nine patients
      underwent immediate maxillary reconstruction and 11 patients underwent secondary
      reconstruction. The overall success rate of 24 flaps was 95.8 percent. The
      exposure rate for titanium mesh and the oronasal fistula rate were both 10.5
      percent. The average length of follow-up was 34.7 months. Recurrence occurred in
      only one patient, who died as a result of the disease. Ten patients received
      implant-borne prostheses or removable partial dentures. Excellent or good
      cosmesis and intelligible speech were noted in 19 patients. All patients were
      ultimately able to tolerate a regular or soft diet. CONCLUSIONS: Reconstruction
      of high maxillectomy defects with the fibula osteomyocutaneous flap in
      combination with titanium mesh or a zygomatic implant is a feasible and
      acceptable option with a high success rate, a low complication rate, excellent
      postoperative cosmesis, and well-accepted function.

PMID- 21200210
TI  - Reconstruction of the hypopharynx with the anterolateral thigh flap: defect
      classification, method, tips, and outcomes.
AB  - BACKGROUND: The authors retrospectively reviewed their experience over the past 5
      years with reconstructions of hypopharyngeal defects using anterolateral thigh
      flaps. The purpose of the study was to present a modified classification of
      defects, the method and tips used, and outcomes and morbidities. METHODS: From
      2002 to 2007, 55 anterolateral thigh flaps were harvested for reconstruction of
      hypopharyngeal defects after tumor ablation in 54 patients. Patient age ranged
      from 38 to 77 years (average, 54 years). In 24 cases, free flaps were used for
      reconstruction of circumferential defects; in 28 cases, they were used to
      reconstruct partial defects; and in three cases, they were used to reconstruct
      circumferential and skin defects. RESULTS: Total flap loss occurred in one
      patient and partial flap loss occurred in three patients. Strictures occurred in
      three patients and fistulas occurred in 10. In one case, arterial occlusion was
      noticed postoperatively. The arterial anastomosis was revised and the flap was
      salvaged. In another case, venous occlusion was noticed. The vein was
      reanastomosed with a vein graft and the flap was salvaged. Postoperatively, seven
      patients tolerated a regular diet. The donor site was skin grafted in five cases,
      closed with reverse anterolateral thigh in one case and with retrograde V-Y
      advancement flap in one case, and closed primarily in the rest. There were no
      donor-site complications. CONCLUSION: Reconstruction of the hypopharynx with the
      anterolateral thigh flap offers versatility in the coverage of large and complex
      defects and is associated with minimal donor-site morbidity.

PMID- 21200211
TI  - Supercharged jejunum flap for total esophageal reconstruction: single-surgeon 3
      year experience and outcomes analysis.
AB  - BACKGROUND: Esophageal reconstruction after total esophagectomy remains a
      formidable task irrespective of the conduit chosen. Historically, the gastric
      pull-up and colonic interposition have served as primary choices for such
      defects. However, where the stomach and colon are unavailable or unsuitable, the
      jejunum serves as a reliable alternative for the reconstruction of total
      esophageal defects. METHODS: The authors performed an outcomes analysis of a
      single surgeon's surgical technique and experience. Patients who received
      supercharged pedicled jejunum flaps for reconstruction of total esophageal
      defects over a 3-year period were included in this study. Data were collected
      prospectively evaluating operative technique, length of hospital stay, operative
      time, complications, postoperative diet, and quality-of-life outcomes analysis.
      RESULTS: Five patients underwent supercharged pedicled jejunal flap surgery
      during this study period. All flaps had complete viability and no microvascular
      complications. One patient had a radiographic anastomotic leak detected by barium
      swallow that was reexplored and closed primarily and reinforced with a pectoralis
      advancement flap with subsequent resolution. All patients are currently
      tolerating a regular diet and there are no symptoms of reflux or dumping. No
      conduit strictures or redundancy has been found to date, and there has been no
      need for reoperation in the long term. CONCLUSIONS: The supercharged jejunum flap
      is a reliable alternative to the gastric pull-up and colonic interposition for
      total esophageal reconstruction. In our experience, the key maneuver in this
      technique is a substernal tunnel for the jejunal conduit and exposure of
      recipient vessels and the esophageal stump by means of a manubriectomy, clavicle
      resection, partial first rib resection and, occasionally, a second rib resection.

PMID- 21200212
TI  - Extended vertical rectus abdominis myocutaneous flap for pelvic reconstruction:
      three-dimensional and four-dimensional computed tomography angiographic perfusion
      study and clinical outcome analysis.
AB  - BACKGROUND: The extended vertical rectus abdominis myocutaneous (eVRAM) flap
      includes skin and subcutaneous fat extending from the costal margin to the
      anterior axillary line. The reliability and vascularity of this distal extension
      have been questioned. The authors hypothesized that the eVRAM flap would have
      adequate perfusion throughout the extended portion and be reliable for pelvic
      reconstruction. To evaluate this, the authors conducted a perfusion study on
      eVRAM flaps from cadavers and a retrospective clinical study of outcomes in
      patients. METHODS: In the perfusion study, seven eVRAM flaps were harvested from
      fresh cadavers. Iodinated contrast material was injected into the deep inferior
      epigastric artery of each flap, and three- and four-dimensional computed
      tomography (three-dimensional and four-dimensional computed tomography)
      angiography was performed. In the clinical study, the surgical outcomes of all
      patients who underwent repair of pelvic defects with a pedicled eVRAM flap
      between 2004 and 2008 were retrospectively evaluated. RESULTS: Three-dimensional
      and four-dimensional computed tomography demonstrated connections between
      adjacent intercostal and superior epigastric artery vascular territories that
      provided a robust blood supply to the flap extension. In the eight patients
      included in the clinical study, all flaps demonstrated excellent vascularity and
      survived completely. Two minor complications occurred: a lateral perineal
      dehiscence and hypertrophic scarring of the abdomen. CONCLUSIONS: Four
      dimensional computed tomography angiography demonstrated vascular perfusion
      throughout the eVRAM flaps. Low rates of donor-site and recipient-site
      complications and good distal flap perfusion were observed when a pedicled eVRAM
      flap was used for pelvic reconstruction. The eVRAM flap is a reliable option for
      pelvic reconstruction requiring large tissue volume and/or additional flap reach.

PMID- 21200213
TI  - An anatomical study of the length of the neural pedicle after the bifurcation of
      the thoracodorsal nerve: implications for innervated free partial latissimus
      dorsi flaps.
AB  - BACKGROUND: For innervated functional muscle transplant procedures, it is
      essential to have knowledge about the length of nerve pedicles available for
      nerve anastomosis. For the latissimus dorsi muscle, the thoracodorsal nerve
      divides into two funicles that separately innervate the medial and lateral
      portions of the muscle. This suggests the possibility of a multiple, segmentally
      innervated latissimus dorsi muscle transfer. The branching and length of the
      thoracodorsal nerve distal to the bifurcation have not been described. This
      surgical-anatomical study presents anatomical data on these practical/clinical
      issues. METHODS: Eleven latissimus dorsi muscles were dissected in eight adult
      embalmed human specimens. The thoracodorsal neurovascular bundle was dissected
      from insertion to proximal of the bifurcation. Measurements were taken indirectly
      from standardized photographic images and analyzed with ImageJ and standard
      spreadsheet software. RESULTS: The mean age of the specimens was 66 years. The
      median pedicle length of the lateral part of the muscle was 3.8 cm (range, 2.41
      to 5.93 cm). The median length of the medial branch was 3.49 cm (range, 1.7 to
      5.12 cm). Proximal branching of the medial pedicle of the bifurcation was
      identified in approximately two-thirds of the specimens and had a median of 3.55
      cm (range, 2.54 to 4.68 cm). The veins and arteries showed a similar pattern,
      with a median length slightly less than that of the thoracodorsal nerve.
      CONCLUSION: The separate neurovascular branches and its minimal pedicle length
      make the latissimus dorsi muscle very suitable for single functional free muscle
      transfer, using only the lateral part of the latissimus dorsi muscle, and double
      functional free muscle transfer using only one vascular pedicle.

PMID- 21200214
TI  - A new, validated instrument to evaluate competency in microsurgery: the
      University of Western Ontario Microsurgical Skills Acquisition/Assessment
      instrument [outcomes article].
AB  - BACKGROUND: The authors present a model for microsurgery learning as well as a
      validated instrument to evaluate microsurgical competency. METHODS: Novice
      microsurgeons participated in three 3-hour sessions wherein they completed a
      number of increasingly complex, standardized microsurgical tasks. Performance was
      recorded and graded using a newly developed University of Western Ontario
      Microsurgery Skills Acquisition/Assessment (UWOMSA) instrument. The knot-tying
      and anastomosis modules contained three categories with five-point Likert scales.
      Each learner's performance was assessed by two blinded surgeons. Reznick's
      validated global rating scale for operative performance was utilized to establish
      criterion validity. Within-scale scores were compared via intraclass correlation
      and between-scale scores with Pearson correlation coefficient. Linear regression
      was used to evaluate the effect of various predictors on UWOMSA scores. RESULTS:
      Thirty-seven videos (9.6 hours) were reviewed, including 20 knot-tying sessions
      and 17 anastomoses. Interrater reliability of UWOMSA was high, with an intraclass
      correlation coefficient of 0.75 (0.57, 0.87). The intraclass correlation of the
      global rating scale was 0.79 (0.62, 0.89). Intrarater reliability of the UWOMSA
      was also high, with an intraclass correlation of 0.69 (0.48, 0.83). The
      intraclass correlation of the global rating scale was 0.69 (0.47, 0.84). Measures
      of criterion validity demonstrated strong agreement between UWOMSA and the global
      rating scale (Pearson correlation coefficient, 0.96; p < 0.001). Measures of
      construct validity demonstrated that higher scores on the UWOMSA were associated
      with faster knot tying (p < 0.0001) and higher postgraduate year level (p =
      0.05). CONCLUSIONS: The UWOMSA instrument performed well in terms of reliability
      and validity. Further study is planned to assess the instrument's ability to
      predict microsurgical skills translation to the clinical setting.

PMID- 21200215
TI  - Discussion. A new, validated instrument to evaluate competency in microsurgery:
      the University of Western Ontario Microsurgical Skills Acquisition/Assessment
      instrument [outcomes article].

PMID- 21200216
TI  - Wide abdominal rectus plication abdominoplasty for the treatment of chronic
      intractable low back pain.
AB  - BACKGROUND: A previous report demonstrated that the wide abdominal rectus
      plication abdominoplasty is an effective treatment modality in select patients
      with low back pain who failed to achieve relief with conservative therapy.
      METHODS: The authors studied eight female patients who presented with chronic low
      back pain and marked lower abdominal wall muscular laxity. All had failed to
      respond to conservative management for their chronic back pain. They all
      underwent wide abdominal rectus plication abdominoplasty. Patient selection and
      details of the procedure are discussed. RESULTS: There were no significant
      complications in this series, and all the patients had prompt and prolonged
      alleviation of their back pain. Length of follow-up ranged from 2 to 11 years.
      CONCLUSIONS: Changes in the biomechanics of the lower abdominal musculature as a
      result of the wide abdominal rectus plication abdominoplasty are discussed in the
      context of increasing spinal stability, leading to an alleviation of chronic low
      back pain. An argument is made that this abdominoplasty procedure produces a
      spine-stabilizing effect by (1) tightening the muscles of the lateral abdominal
      complex and thus increasing intraabdominal pressure and (2) increasing the
      efficiency of these muscles so that their effectiveness as spine stabilizers is
      increased. Even though this is a small series, the fact that all the patients
      sustained long-term alleviation of their preoperative chronic back pain suggests
      that the wide abdominal rectus plication abdominoplasty should be considered as
      an option for patients with weak lower abdominal muscles and intractable low back
      pain who have failed conservative management.

PMID- 21200217
TI  - Discussion. Wide abdominal rectus plication abdominoplasty for the treatment of
      chronic intractable low back pain.

PMID- 21200218
TI  - Sensibility following innervated free radial forearm flap for penile
      reconstruction.
AB  - BACKGROUND: The free radial forearm flap has proven to be reliable for penile
      reconstruction. The purpose of this study was to determine whether neurotization
      of this flap improved sensation of the reconstructed penis. METHODS: A long-term
      follow-up study of 45 patients undergoing penile reconstruction using free radial
      forearm flap was performed; 28 of the 45 patients received an innervated flap,
      and 17 received a noninnervated flap. A nerve repair between the dorsal nerve of
      the penis and the lateral antebrachial cutaneous nerve was performed for
      innervation. Sensory testing, including pain perception, temperature perception,
      vibratory threshold, and static two-point discrimination, was performed by one
      blinded examiner in a standardized pattern. RESULTS: Mean follow-up time was 9.1
      years. Mean patient age was 26.4 years (range, 18 to 48 years). Postoperative
      pain perception and vibratory threshold were similar between the two groups in
      the proximal part of the neophallus but were significantly better in the
      innervated flaps (p < 0.01) in the distal part. Noninnervated flaps displayed a
      pattern of increasing sensibility from the distal part toward the proximal part,
      whereas innervated flaps regained sensation throughout. The innervated group had
      a better result of temperature perception and static two-point discrimination in
      both the proximal and the distal parts. CONCLUSIONS: Innervation of free radial
      forearm flap provides improved sensation to the reconstructed penis. If it is
      possible to find the functional recipient nerve, innervation should always be
      conducted.

PMID- 21200219
TI  - The modified Patient and Observer Scar Assessment Scale: a novel approach to
      defining pathologic and nonpathologic scarring.
AB  - BACKGROUND: Scarring is a highly prevalent and multifactorial process, yet no
      studies to date have attempted to distinguish pathologic from nonpathologic
      scarring. METHODS: This article defines and proposes methods of classifying
      pathologic scarring as it pertains to clinical presentation. RESULTS: The authors
      propose a new scar scale that incorporates pain and functional impairment.
      CONCLUSIONS: The modified Patient and Observer Scar Assessment Scale is the first
      of its kind to factor in the functional deficits pain and pruritus of scarring
      into measurements of associated morbidity. This scale has great potential in
      evaluating patient response to treatment and analyzing clinical outcomes.

PMID- 21200220
TI  - Discussion. Secondary refinements of free perforator flaps for lower extremity
      reconstruction.

PMID- 21200221
TI  - A national study to evaluate trends in the utilization of nerve reconstruction
      for treatment of neonatal brachial plexus palsy [outcomes article].
AB  - BACKGROUND: Approximately 4 to 34 percent of infants born with neonatal brachial
      plexus palsy do not recover spontaneously and require surgery. Despite the
      increasing availability of microsurgical nerve repair, the authors hypothesize
      that this condition remains undertreated and that uninsured children and children
      with public insurance are less likely to receive treatment than those with
      private insurance. METHODS: The authors used a national sample of inpatient
      hospital discharge data from the Healthcare Cost and Utilization Kids Inpatient
      Databases for the years 1997, 2000, 2003, and 2006. Relevant discharges were
      identified using the International Classification of Diseases, Ninth Revision
      diagnosis code 767.6 for neonatal brachial plexus palsy and procedure codes
      relating to nerve surgery. Weighted frequencies were calculated to generate
      national estimates for neonatal brachial plexus palsy births and nerve surgery
      procedures for these patients. RESULTS: A total of 21,758 births with neonatal
      brachial plexus palsy and 721 admissions for nerve surgery were identified. Over
      time, utilization of nerve surgery procedures has generally increased (1.1
      percent in 1997 to 3.2 percent in 2006). Treatment with nerve surgery varied
      significantly according to insurance status-3.8 percent among private insurance
      discharges, 2.9 percent among Medicaid insurance discharges, and 0.7 percent
      among self-pay/uninsured records (p < 0.001). The mean age among nerve surgery
      patients was 235 +/- 75 days, and the mean total charges associated with
      microsurgical intervention was $24,534 +/- $30,460. CONCLUSIONS: Over the past
      decade, approximately 3.3 percent of neonatal brachial plexus palsy births have
      undergone some form of primary microsurgical nerve surgical intervention, which
      may reflect underutilization of these procedures and limited access to care.
      Insurance status plays a significant role in the use of nerve surgery procedures,
      as neonates without private insurance were less likely to receive nerve surgery
      procedures than those with private insurance.

PMID- 21200222
TI  - A single-institution experience of hand surgery litigation in a major
      replantation center.
AB  - BACKGROUND: Bellevue Hospital Medical Center is a level 1 trauma center in New
      York and a major referral center for complex hand injuries and amputations. These
      injuries typically occur at the workplace and are thought to be highly litiginous
      in nature. This study was conducted to analyze the cases involving hand surgery
      litigation related to trauma over the last 8 years at this institution. METHODS:
      The authors performed a retrospective chart review of all claims filed against
      Bellevue Hospital Medical Center after treatment for a hand injury during 2001 to
      2009. Twenty-three patients in total were identified and reviewed for age,
      mechanism/type of injury, complications, decision to replant, average time after
      injury to post claim, and whether settlement was obtained. RESULTS: One of 23
      patients who filed suit against Bellevue Hospital Medical Center received a
      successful settlement involving an incident surrounding the loss of a
      nonreplantable part. Of 168 patients in whom 219 replantations/revascularizations
      were performed, five patients filed claims, all surrounding a failed attempt. In
      total, there were seven complications: five failed replants, one failed thenar
      flap, and one patient who needed a revision completion amputation. CONCLUSIONS:
      The majority of the patients who filed claims did so because of the decision not
      to replant. Only 2.98 percent (five of 168) of all attempted
      revascularization/replantation patients filed claims against the authors'
      institution; all claims were notably dropped. The legal system appears to support
      physicians and institutions that treat these complex injuries. Better patient
      understanding of the decision-making process and complications involving
      treatment of traumatic hand injuries may decrease the number of future lawsuits.

PMID- 21200223
TI  - The free peroneal perforator-based sural neurofasciocutaneous flap: a novel tool
      for reconstruction of large soft-tissue defects in the upper limb.
AB  - BACKGROUND: The sural neurofasciocutaneous flap has been widely used for
      reconstruction of soft-tissue defects in the lower leg, ankle, and foot. It can
      provide a large amount of tissue without compromising the function of the leg.
      The authors report the applications of the free peroneal perforator-based sural
      neurofasciocutaneous flap. METHODS: The free sural neurofasciocutaneous flap
      based on a single peroneal perforator is described. The peroneal perforator,
      which emerges from the posterior crural septum at the junction of middle and
      lower thirds of the fibula, was chosen as the pedicle of the flap. Six perforator
      based sural neurofasciocutaneous flaps were transferred to resurface large soft
      tissue defects in the upper limb. The size of the defects ranged from 15 * 6 cm
      to 45 * 10 cm. RESULTS: All six flaps survived completely without necrosis. The
      area of the flaps ranged from 16 * 8 cm to 30 * 10 cm. The average diameter of
      the peroneal perforator ranged from 1.0 to 1.5 mm, and the length of the
      perforator pedicles ranged from 4 to 6 cm. One patient developed arterial
      thrombosis after surgery, which was treated by removal of the thrombus and
      reanastomosis. No severe venous congestion was observed. All the patients were
      satisfied with the aesthetic outcome postoperatively at 3 to 12 months' follow
      up. There were no serious donor-site complications. CONCLUSION: The free
      perforator-based sural neurofasciocutaneous flap is a good alternative for
      reconstruction of extensive soft-tissue defects in the upper limb.

PMID- 21200224
TI  - A phenotypic assessment tool for craniofacial microsomia.
AB  - BACKGROUND: Craniofacial microsomia is one of the most common conditions treated
      by craniofacial teams. However, research regarding the cause of this condition or
      the surgical outcomes of treatment is scant. This is attributable to the lack of
      diagnostic criteria and the wide phenotypic spectrum. Standardized description of
      the craniofacial malformations associated with craniofacial microsomia is a
      necessary first step for multicenter, interdisciplinary research into this
      complex condition. METHODS: The authors used the previously published pictorial
      Orbit, Mandible, Ear, Nerve, and Soft tissue-Plus classification scheme to assign
      a phenotypic severity score to patients with craniofacial microsomia treated at
      the Craniofacial Center at Seattle Children's Hospital. The authors modified the
      tool based on feedback from multidisciplinary focus groups. The authors also
      developed a standardized photographic protocol to facilitate assessment of
      patients using two-dimensional images. RESULTS: Feedback from focus groups was
      synthesized to create a phenotypic assessment tool for craniofacial microsomia
      based on the pictorial Orbit, Mandible, Ear, Nerve, and Soft tissue-Plus
      classification system. This tool allows for more comprehensive description of the
      phenotype of craniofacial microsomia and is found to be effective for clinical
      use within a multidisciplinary craniofacial team. In addition, the photographic
      protocol for patients with craniofacial microsomia allows for classification from
      a two-dimensional photographic database, thereby facilitating research using
      archived photographs. CONCLUSIONS: The phenotypic assessment tool for
      craniofacial microsomia protocol provides a simple and standardized method for
      practitioners and researchers to classify patients with craniofacial microsomia.
      We anticipate that this tool can be used in multicenter investigational studies
      to evaluate the cause of this condition, its natural history, and comparative
      effectiveness research.

PMID- 21200225
TI  - Inlay implanting technique for the correction of medial orbital wall fracture.
AB  - BACKGROUND: For blowout fractures of the medial orbital wall, the goals of
      treatment are complete reduction of the herniated soft tissue and anatomical
      restoration of the orbital wall without surgical complications. Surgeons
      frequently worry about damage to the optic nerve caused by dissection when the
      part over the posterior ethmoidal foramen is fractured. The authors performed
      small incision and inlay implantation of porous polyethylene for reconstruction
      of medial orbital wall fractures. METHODS: Between January of 2007 and December
      of 2009, 55 patients were included in an analysis of the outcome of corrected
      medial orbital wall fractures. For 55 patients with posterior comminuted
      fractures of the medial orbital wall, insertion of porous polyethylene into the
      ethmoid sinus was performed in multiple layers, through the transconjunctival
      approach. RESULTS: In all cases, the orbital cavity was restored to its normal
      anatomical shape. The associated ocular problems disappeared except for mild
      enophthalmos in three patients and diplopia in one patient. There were no serious
      surgical complications associated with inlay implantation. CONCLUSIONS: The
      advantages of the inlay technique include the anatomical reconstruction of the
      orbital wall, the avoidance of optic nerve injury, the simplicity of the
      procedure, and consequently the absence of surgery-related complications. This
      technique is presented as one of the preferred treatments for posterior
      comminuted fractures of the medial orbital wall.

PMID- 21200226
TI  - Changing patterns in demography of cleft lip-cleft palate deformities in a
      developing country: the Smile Train effect--what lies ahead?
AB  - BACKGROUND: The past decade has seen tremendous changes in the management of
      cleft deformities with the advent of the Smile Train project. The present study
      evaluates the effect of the Smile Train project on the demographics of cleft
      deformities. METHOD: Data collected over the past three decades were studied
      retrospectively. The number of cases, age at presentation, and relative
      proportion of cleft lip-cleft palate patients were analyzed. Thirty patients
      operated on at the authors' institute for cleft lip deformity were evaluated for
      their awareness of cleft deformities, and the results were compared with those of
      22 patients operated on elsewhere in camp settings. RESULTS: The numbers of
      patients with cleft deformities treated at the authors' institute from 1980 to
      1989, 1990 to 1999, and 2000 to 2009 were 1189, 1050, and 374, respectively.
      However, the number with cleft palate has remained nearly constant over the three
      decades. The mean age of reporting for treatment of cleft palate was 16 months
      after being operated on for cleft lip at the authors' institute and 41 months
      after being operated on elsewhere in camps. All patients operated on at the
      authors' institute expressed awareness of holistic treatment of cleft
      deformities. Of the 22 patients operated on at other camps, 16 were ignorant
      about the time scale and 19 were unaware of the consequences of nonadherence to
      the treatment protocol. Nineteen of the 22 patients felt that enough information
      was not provided to them at initial surgery. CONCLUSION: The authors recommend
      that cleft counseling, continued cleft care for the complete complex of
      deformities, and responsible behavior by the initial operating team should be the
      goals for the future.

PMID- 21200227
TI  - A microcosting approach for isolated, unilateral cleft lip care in the first year
      of life.
AB  - BACKGROUND: The concept of value-based health care underlies many new improvement
      initiatives in U.S. health care. To determine value, accurate measures of both
      outcomes and costs are essential, which may then be compared for the same
      provider or system over time or between providers, to foster improvement.
      Although outcomes measurement has received a great deal of attention since the
      quality movement began in the United States, costing methodologies are lacking.
      METHODS: A basic microcosting methodology was used to obtain direct medical
      costs, including physician compensation, for individuals with isolated,
      unilateral cleft lip deformity receiving their full course of care from one
      surgeon. The authors analyzed costs associated with the timeline of care during
      the first year of life. RESULTS: The median cost for the first year of life was
      $13,013 (range, $10,426 to $16,115; n = 12). Ninety-one percent of costs were
      associated with the cleft lip repair, which occurred at a median age of 3.7
      months. The majority of these costs stemmed from time in the operating room and
      the inpatient stay, which accounted for 68 and 19 percent of first-year costs,
      respectively. CONCLUSIONS: Using a microcosting approach, the authors identified
      specific cost drivers and outlined a distinct timeline of care for patients with
      isolated cleft lip in the first year of life. This approach may serve as a
      template for the cost side of the value equation, for which accurate
      methodologies are needed. When combined with key outcomes measures, it will be
      possible to measure and improve value at the patient and provider levels.

PMID- 21200228
TI  - How do the type and location of a vascular malformation influence growth in
      Klippel-Trenaunay syndrome?
AB  - BACKGROUND: Although Klippel-Trenaunay syndrome is a mixed vascular malformation
      characterized by abnormal growth in the extremities, no uniform diagnostic
      criteria have been established because of the variety in its manifestation.
      Consequently, no anatomical analysis based on a comparison study has been
      reported. In this study, the authors determine the frequency of various vascular
      malformations and abnormal growth and assess any statistical relationship between
      vascular malformation type/location and abnormal growth in terms of length and
      girth. METHODS: Thirty-five patients with Klippel-Trenaunay syndrome satisfying
      the criteria proposed by Oduber et al. in 2008 were enrolled. The type and
      location of the vascular malformation and abnormal circumferential growth were
      assessed by magnetic resonance imaging and ultrasonography. Bone girth was
      assessed by axial magnetic resonance imaging/computed tomography. Plain
      radiographs of the long bones were used to measure growth in length. RESULTS: The
      spectrum of vascular types was similar to that in previous reports. There was no
      significant association between leg length and vascular malformation type or
      location. Leg bone circumferential hypoplasia was observed in 50 percent of cases
      and was significantly related to the presence of intramuscular lesions. A single
      venous malformation in the subcutaneous tissue was significantly associated with
      the presence of subcutaneous hypertrophy. Patients with intramuscular lymphatic
      malformations had a significantly higher frequency of muscle hypoplasia.
      CONCLUSION: The type and location of certain vascular malformations were
      significantly associated with abnormal subcutaneous tissue, muscle, and bone
      growth.

PMID- 21200229
TI  - Evaluation of terminology for vascular anomalies in current literature.
AB  - BACKGROUND: A binary classification of vascular anomalies was approved 14 years
      ago by the International Society for the Study of Vascular Anomalies. The purpose
      of this study was to determine whether the International Society for the Study of
      Vascular Anomalies system is being used to categorize anomalies, and whether
      incorrect nomenclature affects patient care. METHODS: The PubMed database was
      searched for English language publications with the term "hemangioma" in the
      title/abstract during 2009. Outcome variables were (1) whether accepted
      nomenclature was used to describe the vascular anomaly and (2) whether or not
      patients received incorrect treatment. Predictive variables for terminological
      accuracy were patient age, location of the anomaly, and the primary author's
      medical specialty. RESULTS: "Hemangioma" was used incorrectly in 71.3 percent
      (228 of 320) of publications. Patients whose lesions were mislabeled were more
      likely to receive improper treatment (20.6 percent) compared with subjects whose
      lesions were designated using International Society for the Study of Vascular
      Anomalies terminology (0.0 percent) (p = 0.001). The patients were younger in
      articles that properly identified hemangioma (4.1 months) compared with articles
      that used hemangioma to describe another anomaly (36.1 years) (p < 0.0001).
      Publications focused on integument/soft-tissue lesions were more accurate (57.4
      percent) than those in other anatomical areas (86.3 percent) (p < 0.0001). The
      erroneous use of hemangioma was independent of the authors' discipline:
      pediatrics (60.0 percent), internal medicine (61.4 percent), surgery (68.9
      percent), and obstetrics/gynecology (70.0 percent) (p = 0.68). CONCLUSIONS:
      Hemangioma continues to be commonly misused to describe any type of vascular
      anomaly, and terminological imprecision is prevalent among both medical and
      surgical fields. Inaccurate designation of the vascular anomaly is associated
      with an increased risk of erroneous management.

PMID- 21200230
TI  - Salvage of the crucified chin.

PMID- 21200231
TI  - Modified deep plane rhytidectomy with a lateral approach to the neck: an
      alternative to submental incision and dissection.
AB  - BACKGROUND: A "composite" type subplatysmal dissection with lateral advancement
      of the platysma-skin flap to lift the neck during rhytidectomy has been advocated
      by several authors. However, the limited subplatysmal dissection described in
      these techniques restricts the degree of mobilization of the flap. Therefore,
      most investigators rely on supraplatysmal dissection and medial plication of the
      platysma to achieve satisfactory cervical contours, especially in patients with
      difficult necks. METHODS: To allow for greater mobilization of composite neck
      flaps, the senior author (T.A.M.) extends the subplatysmal dissection to
      incorporate release of cervical retaining ligaments. The dissection is carried
      medially to just beyond the region defined by the inferomedial portion of the
      parotid gland, and inferiorly to where the superficial musculoaponeurotic system
      platysma layer and greater auricular nerve cross the posterior border of the
      sternocleidomastoid muscle. Dissection of the composite flap is followed by use
      of fine cannula submental liposuction. RESULTS: Experience with 742
      rhytidectomies performed over a 10-year period indicates that this operation can
      be completed safely with satisfactory results and a low incidence of
      complications. The use of a submental incision and medial platysma plication can
      be avoided almost entirely. CONCLUSIONS: Identification and release of the
      cervical retaining ligaments permits significant platysma-skin flap mobilization.
      When complemented with submental liposuction, complete cervical rejuvenation can
      be achieved without need for medial platysma plication. The full integration of
      the neck and facial plane of dissection results in a very even tension and a
      natural appearance, even in repeated face lifts.

PMID- 21200232
TI  - Discussion. Modified deep plane rhytidectomy with a lateral approach to the neck:
      an alternative to submental incision and dissection.

PMID- 21200233
TI  - Discussion. Aging of the facial skeleton: aesthetic implications and rejuvenation
      strategies.

PMID- 21200234
TI  - An integrated approach to lower blepharoplasty.
AB  - BACKGROUND: Limitations associated with traditional skin-muscle flaps and later
      with transconjunctival fat resection combined with carbon dioxide laser
      resurfacing have led to newer concepts in lower blepharoplasty that emphasize fat
      preservation, blending of the lid-cheek junction, simplified skin excision, and
      less morbid resurfacing techniques. Avoiding incision through the orbicularis
      muscle to preserve its innervation and reduce translamellar scarring is favored,
      as is a more liberal use of lateral canthal tightening procedures. This study
      investigates the use of a transconjunctival approach to resect and transpose fat
      combined with a skin flap technique that permits skin excision and simultaneous
      resurfacing with 30% trichloroacetic acid. The orbicularis is not violated and
      lateral canthal support is used as necessary. METHODS: Lower blepharoplasty
      performed in 248 patients over a 4-year period was studied. The technique
      consisted of component procedures that varied based on individual anatomy.
      RESULTS: Fat excision was performed in 91 percent, fat transposition was
      performed in 61 percent, skin excision was performed in 63 percent,
      trichloroacetic acid peels were performed in 62 percent, temporary tarsorrhaphy
      was performed in 31 percent, and lateral canthopexy was performed in 18 percent
      of patients. Average follow-up was 5.5 months. There were three complications and
      six revisions. CONCLUSIONS: Lower blepharoplasty that integrates component
      techniques tailored to individual anatomical problems and spares the orbicularis
      muscle is effective and associated with few complications and revisions. Fat
      transposition achieves effacement of the tear trough deformity. A skin flap
      approach effectively treats rhytides and is safe for simultaneous resurfacing
      with a mild peeling agent. Selective use of lateral canthal support improves
      lower eyelid tone and prevents malposition problems.

PMID- 21200235
TI  - Vertical enlargement of the palpebral aperture by static shortening of the
      anterior and posterior lamellae of the lower eyelid: a cosmetic option for Asian
      eyelids.
AB  - BACKGROUND: Although double eyelid plasty, levator aponeurotic surgery, and
      epicanthoplasty are well-accepted cosmetic treatments for Asian eyes, some
      patients are incompletely satisfied with the outcomes and request further
      surgery. Although lower eyelid descent is generally recognized as a symptom of
      aging or a complication after blepharoplasty, the authors propose a perceptional
      change: a lowering the lower eyelid procedure to vertically enlarge the palpebral
      aperture in selected Asian patients. METHODS: A total of 125 Japanese patients
      underwent the lowering the lower eyelid procedure between 2005 and 2009. The main
      indications were patients with vertically narrow palpebral aperture or an up
      slanting appearance. The lowering the lower eyelid procedure is performed by a
      combination of the removal of approximately 4 to 6 mm of the subciliary skin
      (usually the lateral one-third to two-thirds of the lower eyelids) and static
      shortening of the lower eyelid retractors (posterior lamella) through a
      transconjunctival approach. The middle lamella was not touched during the
      procedure. RESULTS: The up-slanting lower eyelid margin was lowered and the
      lateral part of the palpebral aperture was enlarged by the procedure in all
      cases. Cosmetic outcomes were encouraging and satisfying to most patients. Three
      complications occurred (2.4 percent): lagophthalmos in one patient (0.8 percent)
      and entropion in two patients (1.6 percent). These minor complications resolved
      within 1 month. Eight revision operations were required for undercorrection.
      CONCLUSIONS: The lowering the lower eyelid procedure offers Asian patients
      desiring large oval eyes a novel surgical option. The procedure proved to be a
      reliable and consistent technique that provided satisfactory results in carefully
      selected patients.

PMID- 21200236
TI  - Discussion. Vertical enlargement of the palpebral aperture by static shortening
      of the anterior and posterior lamellae of the lower eyelid: a cosmetic option for
      Asian eyelids.

PMID- 21200237
TI  - Form stability of the Style 410 anatomically shaped cohesive silicone gel-filled
      breast implant in subglandular breast augmentation evaluated with magnetic
      resonance imaging.
AB  - BACKGROUND: In this study, the authors evaluated the form stability of the Style
      410 anatomically shaped cohesive silicone gel-filled breast implant after
      subglandular implantation. METHODS: Nine women who had undergone bilateral
      subglandular breast augmentation using Style 410 implants were examined in the
      prone and supine positions with magnetic resonance imaging. RESULTS: In the
      supine position, the dimensions of the implants were similar to those specified
      by the manufacturer. In the prone position, there was a mean increase of 29.5
      percent (range, 9.7 to 53.3 percent) in implant projection. All implants had
      their point of maximal projection positioned in the lower pole in both positions.
      CONCLUSIONS: The Style 410 implant is described as a form-stable, anatomically
      shaped, cohesive, silicone gel-filled implant. However, its shell and the degree
      of silicone gel cohesivity allow for a change in form depending on body posture.
      Compared with the supine position, there was a marked increase in implant
      projection in the prone position. The Style 410 implant keeps its lower pole
      fullness after subglandular implantation in both the supine and prone positions.

PMID- 21200238
TI  - Discussion. Form stability of the Style 410 anatomically shaped cohesive silicone
      gel-filled breast implant in subglandular breast augmentation evaluated with
      magnetic resonance imaging.

PMID- 21200239
TI  - Comparison of seroma formation following abdominoplasty with or without
      liposuction.
AB  - BACKGROUND: In light of the scarce literature published regarding seroma
      formation following abdominoplasty when performed with or without liposuction,
      the objective of this study was to determine whether abdominoplasty performed in
      conjunction with flank liposuction confers an increased risk for seroma formation
      compared with abdominoplasty alone. METHODS: This was a retrospective cohort
      study of 200 patients who underwent abdominoplasty with or without liposuction
      from 2004 to 2007. Medical records were reviewed to collect data regarding
      patient demographics, length of drain use, operative technique, seroma formation,
      and other complications. Seroma formation was determined by physical examination
      1 week after closed-suction drain removal. Logistic regression analysis was used
      to determine independent predictors of seroma formation. Results were considered
      significant for values of p < 0.05. RESULTS: One hundred twenty-five patients
      underwent abdominoplasty with flank liposuction and 75 patients underwent
      abdominoplasty alone. The incidence of seroma formation was 16.0 percent in the
      abdominoplasty-alone group and 31.2 percent in the abdominoplasty with
      liposuction group (p < 0.05). The mean age was 43.1 +/- 10.2 years and the mean
      body mass index was 27.3 +/- 5.4 kg/m2. Increasing body mass index (odds ratio,
      1.1; 95 percent confidence interval, 1.02 to 1.17) and liposuction of the flanks
      (odds ratio, 3.3; 95 percent confidence interval, 1.37 to 7.97) were independent
      and significant predictors of seroma formation in abdominoplasty patients.
      CONCLUSIONS: Patients should be counseled regarding an increased risk of seroma
      formation following abdominoplasty when combined with liposuction of the flanks.
      In addition, patients who are overweight are at increased risk for developing a
      postoperative seroma compared with patients with normal body mass indices.

PMID- 21200240
TI  - A systematic review of comparison of efficacy and complication rates among face
      lift techniques.
AB  - BACKGROUND: The ideal face lift has the longest efficacy, the fewest
      complications, and ultimately, the highest patient satisfaction. With so many
      different techniques, there exists a need to make this comparison and to
      establish which approaches may work best in various groups. To date, there has
      been no systematic review to study the efficacy and complication rates among
      different face-lift techniques. This study aims to make this comparison. METHODS:
      A systematic search of the English language literature listed in the MEDLINE
      (Ovid MEDLINE 1950 to November of 2009 with Daily Update), PubMed, and Cochrane
      Central Register of Controlled Trials (CENTRAL) databases yielded trials on
      comparison of different face-lift techniques in their efficacy and complication
      rates. All relevant articles' reference sections were studied for additional
      relevant publications. RESULTS: The keyword search yielded 39 articles. Eighteen
      more articles were retrieved from reference sections of relevant articles. Only
      10 articles made a direct comparison of efficacy between face-lift techniques,
      and only five articles made a direct comparison of complications between face
      lift techniques. CONCLUSIONS: Although this systematic review revealed a lack of
      quality data in comparing the efficacy and safety among different face-lift
      techniques, it is important to review and pool the existing studies to improve
      patient outcomes. This analysis has also shown the need for better studies,
      especially randomized, prospective, controlled studies, and a need for a
      standardized method of efficacy analysis and patient-reported outcomes measures
      to allow objective comparison of face-lift techniques.

PMID- 21200241
TI  - Statistics in medicine.
AB  - The scope of biomedical research has expanded rapidly during the past several
      decades, and statistical analysis has become increasingly necessary to understand
      the meaning of large and diverse quantities of raw data. As such, a familiarity
      with this lexicon is essential for critical appraisal of medical literature. This
      article attempts to provide a practical overview of medical statistics, with an
      emphasis on the selection, application, and interpretation of specific tests.
      This includes a brief review of statistical theory and its nomenclature,
      particularly with regard to the classification of variables. A discussion of
      descriptive methods for data presentation is then provided, followed by an
      overview of statistical inference and significance analysis, and detailed
      treatment of specific statistical tests and guidelines for their interpretation.

PMID- 21200242
TI  - Eponymous instruments in plastic surgery.
AB  - Surgeons use eponymous instruments daily, yet the stories behind these
      instruments are often lost in history. The authors have selected eponymous
      instruments commonly used in plastic surgery and provide a brief biography of the
      surgeons who invented them. This list represents more than two centuries of
      surgical history, and the physicians come from a number of disciplines, including
      general surgery, plastic surgery, ophthalmic surgery, and rural medicine.
      Remembering the life stories of surgeon inventors enriches our understanding of
      the history of our profession and allows us to appreciate our instruments instead
      of taking them for granted.

PMID- 21200243
TI  - So you want to be an evidence-based plastic surgeon? A lifelong journey.

PMID- 21200244
TI  - Fat grafting to the breasts: plastic surgery's "disruptive technology"?

PMID- 21200247
TI  - Preventing tip modifications and alar retractions: the "joy-ride" stitch.

PMID- 21200250
TI  - Branching point of the cervical motor branch of the facial nerve.

PMID- 21200252
TI  - Internal fixation of mandibular angle fractures: a meta-analysis.

PMID- 21200253
TI  - Acellular human dermis implantation in 153 immediate two-stage tissue expander
      breast reconstructions: determining the incidence and significant predictors of
      complications.

PMID- 21200254
TI  - Augmentation of venous drainage in DIEP flaps.

PMID- 21200257
TI  - The three breast dimensions: analysis and effecting change.

PMID- 21200258
TI  - The role of inconstant perforating arteries in harvesting radial flaps.

PMID- 21200260
TI  - Multivariate predictors of failure after flap coverage of pressure ulcers.

PMID- 21200261
TI  - Hydrogen sulfide attenuates ischemia-reperfusion injury in in vitro and in vivo
      models of intestine free tissue transfer.

PMID- 21200264
TI  - Current concepts in wound healing: update 2011.

PMID- 21200266
TI  - Preface to Current concepts in wound healing: update 2011.

PMID- 21200267
TI  - The role of stem cells in cutaneous wound healing: what do we really know?
AB  - Wound repair is a complex process involving the orchestrated interaction of
      multiple growth factors, cytokines, chemokines, and cell types. Dysregulation of
      this process leads to problems such as excessive healing in the form of keloids
      and hypertrophic scars and chronic, nonhealing wounds. These issues have broad
      global implications. Stem cells offer enormous potential for enhancing tissue
      repair and regeneration following injury. The rapidly developing fields of stem
      cell biology and skin tissue engineering create translational opportunities for
      the development of novel stem cell-based wound-healing therapies.

PMID- 21200268
TI  - Biomarkers to predict wound healing: the future of complex war wound management.
AB  - BACKGROUND: Currently, no biological assay exists to objectively assess wounds to
      aid in timing of wound closure and guide therapy. In this article, the authors
      review military investigations in biomarkers as a method of objectively
      determining acute traumatic wound physiology and their applicability in
      predicting healing of complex soft-tissue wounds. METHODS: The civilian
      literature related to biomarkers and wound physiology related to chronic and
      acute wounds was reviewed as a basis for current research into acute traumatic
      soft-tissue wounds. RESULTS: Analysis of serum and wound effluent from traumatic
      extremity soft-tissue combat wounds revealed changes in specific proinflammatory
      matrix metalloproteinases associated with impaired wound healing. Forsberg et al.
      analyzed serum and wound effluent for chemokines and cytokines. An increase in
      serum procalcitonin levels correlated with wound dehiscence. Lastly, serum, wound
      effluent, and wound bed tissue biopsy specimens were analyzed by Hawksworth et
      al. Consistent with previous studies, elevation in proinflammatory cytokines was
      associated with wound dehiscence. CONCLUSIONS: Changes in levels of proteases,
      protease inhibitors, and inflammatory markers have been correlated with wound
      healing. These findings further support the idea that inflammatory dysregulation
      and a persistent inflammatory state leads to failure of wound healing in the
      acute setting. These findings highlight potential targets for the development of
      a biological assay to individualize management of complex soft-tissue wounds,
      based on patient physiology and response, that would be applicable to not only
      military trauma but also civilian trauma. Ultimately, this would result in
      earlier wound closure, reduction in the number of operating room trips, and
      reduced health care costs.

PMID- 21200269
TI  - Discussion. Biomarkers to predict wound healing: the future of complex war wound
      management.

PMID- 21200270
TI  - The role of biofilms: are we hitting the right target?
AB  - BACKGROUND: Chronic infections affect 17 million people yearly, and approximately
      550,000 people die each year from, or with, their chronic infections. Acute and
      chornic infection differences are well known to clinicians, but the role of
      bacteria in producing these clinical differences remains poorly understood.
      METHODS: This review relies on basic science, clinical studies, and a general
      review of the medical biofilm literature. The basic science studies are level A
      and B quality of evidence. The clinical studies are mainly retrospective cohort
      (level B) and case studies (level C). The biofilm literature includes reviews
      with varying levels of evidence. All articles have been peer reviewed and meet
      the standard of evidence-based medicine. RESULTS: Acute infections are associated
      with planktonic bacteria and must be diagnosed rapidly and accurately to prevent
      tissue damage and/or death. In contrast, biofilm behavior pursues a more
      parasitic course by producing sustained host hyperinflammation, with the biofilm
      feeding on plasma exudate. Chronic infections vacillate over long periods of
      time, responding only partially to antibiotics and reemerging once the
      antibiotics are withdrawn. Chronic wounds exhibit similar clinical behavior seen
      in other chronic infections and are associated with biofilm phenotype bacteria on
      their surface. Biofilm infections, such as chronic wounds, cannot be adequately
      diagnosed with current clinical cultures; therefore, molecular methods are
      necessary. CONCLUSIONS: Biofilm phenotype bacteria require multiple concurrent
      strategies, including debridement and targeted antibiofilm agents. Biofilm
      phenotype bacteria predominate on the surface of wounds, and biofilm-based
      management improves wound healing outcomes, indicating that biofilm is the right
      target for managing the bioburden barrier of chronic wounds.

PMID- 21200271
TI  - Discussion. The role of biofilms: are we hitting the right target?

PMID- 21200272
TI  - Nutrition and wound healing: an update.
AB  - Nutrition has always been noted to be one of the major influences on the
      successful outcome of wound healing. The exuberant cellular and biochemical
      events that constitute the wound-healing cascade require energy, amino acids,
      oxygen, metals, trace minerals, and vitamins for successful completion. Many
      nutritional deficiencies impact on wound healing by impeding fibroblast
      proliferation, collagen synthesis, and epithelialization. There are also
      nutrients that can enhance wound-healing responses. It is imperative for
      physicians to obtain a complete nutritional history and consider nutritional
      intervention as a means of affecting the course of healing. This review examines
      many of the advances that have occurred in understanding nutrition/wound
      interactions.

PMID- 21200273
TI  - State of the art in topical wound-healing products.
AB  - Chronic wounds represent a significant medical burden. Such wounds fail to
      normally progress through the stages of healing, often complicated by a
      proinflammatory milieu caused by increased proteinases, hypoxia, and bacterial
      burden. As a result, several modalities, such as dressings, antimicrobials,
      growth factors, and human skin substitutes, have been devised in an attempt to
      correct the chronic wound environment. This review addresses these modalities
      with a focus on evidence and randomized controlled trials.

PMID- 21200274
TI  - Template for skin regeneration.
AB  - BACKGROUND: Advances in critical care allowed survival of large total body
      surface burn patients in the 1970s, spawning the development of artificial skin
      for burn victims. Lack of dermis resulted in severe scarring and contractures.
      The physicochemical properties that are critical to dermal regeneration have
      subsequently been described, and a dermal regeneration template has been
      developed. METHODS: The peer-reviewed literature regarding the basic science and
      clinical use of dermal regeneration template was reviewed, as was our practical
      experience in using dermal regeneration template. RESULTS: Dermal regeneration
      template has been effective in treating large areas of skin loss in burn victims
      and has been shown to have scar reductive and regenerative properties. Its use
      has been extended to reconstructive burns, including scar revisions and the
      treatment of burn scar contractures. It has also been useful in treating small
      areas of exposed bone, tendon, or joints and a variety of acute and chronic
      wounds. Meticulous wound bed preparation and close monitoring of the dermal
      regeneration template is critical to successful use. CONCLUSIONS: Dermal
      regeneration template provides a novel element to add to the reconstructive tools
      used today by plastic surgeons. Further development of these technologies may
      allow for improved regenerative capacity of these devices to allow optimal
      aesthetic and functional results of dermal reconstruction.

PMID- 21200275
TI  - Discussion. Template for skin regeneration.

PMID- 21200276
TI  - Bioengineered skin constructs and their use in wound healing.
AB  - BACKGROUND: Over the past two decades, the field of wound healing and tissue
      repair has witnessed tremendous advances resulting from the biological sciences,
      biomedical and tissue engineering, and greater clinical understanding of wounds
      and their pathophysiology. In large part because of these advances, clinicians
      are now able to offer and deliver more sophisticated and effective treatments to
      patients with acute wounds, chronic wounds, burns, and other types of injuries.
      METHODS: This report relies on published information focused on bioengineered
      skin and the authors' perspectives on the application of this technology in wound
      healing. In some cases, off-label applications of certain bioengineered skin
      constructs have been used to illustrate the spectrum of usefulness of these
      constructs. RESULTS: Bioengineered skin (including acellular and cellular
      products; living and nonliving constructs; and epidermal, dermal, and bilayered
      therapeutic adjuncts) has resulted in very substantial and demonstrable
      improvements in wound care. Some of the constructs are U.S. Food and Drug
      Administration approved for treatment of burns and for impaired healing
      situations, including venous and diabetic foot ulcers. CONCLUSIONS: The advances
      that have occurred in testing and proving the efficacy of bioengineered skin hold
      great promise for further improvements in the way this technology is used in the
      surgical field and in wound care. Advances in therapeutic agents have also led to
      greater understanding of pathophysiology. Thus, wound bed preparation as a
      concept and as an approach is in fact the result of the need to maximize the
      benefits of advanced therapies.

PMID- 21200277
TI  - Discussion. Bioengineered skin constructs and their use in wound healing.

PMID- 21200278
TI  - Current status of the use of modalities in wound care: electrical stimulation and
      ultrasound therapy.
AB  - Wound healing is a complex pathway that requires cells, an appropriate
      biochemical environment (i.e., cytokines, chemokines), an extracellular matrix,
      perfusion, and the application of both macrostrain and microstrain. The process
      is both biochemically complex and energy dependent. Healing can be assisted in
      difficult cases through the use of physical modalities. In the current
      literature, there is much debate over which treatment modality, dosage level, and
      timing is optimal. The mechanism of action for both electrical stimulation and
      ultrasound are reviewed along with possible clinical applications for the plastic
      surgeon.

PMID- 21200279
TI  - Discussion. Current status of the use of modalities in wound care: electrical
      stimulation and ultrasound therapy.

PMID- 21200280
TI  - Update on negative-pressure wound therapy.
AB  - BACKGROUND: Over the last 15 years, negative-pressure wound therapy has become
      commonly used for treatment of a wide variety of complex wounds. There are now
      several systems marketed, and additional products will be available in the near
      future. Many clinicians have noted a dramatic response when negative-pressure
      wound therapy technology has been used, prompting a number of scientific
      investigations related to its mechanism of action and clinical trials determining
      its efficacy. METHODS: The peer-reviewed literature within the past 5 years was
      reviewed, using an evidence-based approach. RESULTS: Negative-pressure wound
      therapy works through mechanisms that include fluid removal, drawing the wound
      together, microdeformation, and moist wound healing. Several randomized clinical
      trials support the use of negative-pressure wound therapy in certain wound types.
      Serious complications, including bleeding and infection, have recently been
      reported by the U.S. Food and Drug Administration in a small number of patients.
      CONCLUSIONS: Negative-pressure wound therapy has dramatically changed the way
      complex wounds are treated. The rapid introduction of this technology has
      occurred faster than large-scale randomized controlled studies or registry
      studies have been conducted. Further clinical studies and basic science studies
      will help surgeons to better understand the evidence and use this technology in
      the future.

PMID- 21200281
TI  - Discussion. Update on negative-pressure wound therapy.

PMID- 21200282
TI  - Negative-pressure wound therapy in the military: lessons learned.
AB  - The utilization of negative pressure for medicinal purposes dates back to 600 bc.
      The U.S. military has been engaged in continuous overseas combat operations since
      2001. Negative-pressure wound therapy has been in use in the treatment of
      casualties from these operations since 2004. It represents a new standard of
      practice in combat wound care; it promotes granulation tissue formation and
      creates mechanical forces supporting wound contraction, facilitating definitive
      wound closure. This article describes (1) the use of negative-pressure wound
      therapy in combat casualty care, (2) inherent challenges of its use in theater of
      operations and across the echelons of care, (3) modifications of this wound
      therapy to meet military-specific needs, and (4) future directions with this
      novel wound care modality.

PMID- 21200284
TI  - Discussion. Hyperbaric oxygen: its mechanisms and efficacy.

PMID- 21200285
TI  - The current state of evidence-based protocols in wound care.
AB  - BACKGROUND: Clinical practice guidelines have blossomed in the last 10 years in
      medicine as well as wound care. The physician practicing wound care and
      attempting to use published clinical practice guidelines may, however, have
      difficulty judging the quality of these guidelines given legitimate concerns that
      many aspects of clinical practice guidelines are not being properly addressed.
      METHODS: Guidelines were located using the National Guideline Clearinghouse Web
      site, PubMed, and the Cochrane database for reviews on diabetic foot ulcers,
      venous ulcers, and pressure ulcers. The Appraisal of Guidelines for Research and
      Evaluation instrument was used to evaluate guidelines. RESULTS: Search engines
      returned many irrelevant guidelines. Many guidelines would be difficult to
      evaluate by clinicians not versed in guideline evaluation and were cumbersome in
      format or were presented more as reference works. Too little attention is focused
      on such issues as clarity of presentation, consideration of multidisciplinary
      panels, stakeholder involvement, validity, testing, settings, resources required,
      cost impact, methods of addressing guideline implementation, and a means of
      tracking important criteria for feedback once the guideline is in the field. The
      venous and diabetic ulcer guidelines that were formally evaluated scored poorly
      in many of these areas despite using relatively sound methods for gathering and
      evaluating the evidence. Only the developers of one guideline made a commitment
      for regular update. CONCLUSION: Although progress has been made in regard to
      wound care clinical practice guidelines, much more work will be required before
      such guidelines are highly accepted by wound care clinicians.

PMID- 21200286
TI  - Open surgical revascularization for wound healing: past performance and future
      directions.
AB  - The goal of lower extremity revascularization is to relieve pain, heal wounds,
      and prevent amputations by restoration of arterial perfusion. This necessarily
      brief overview will discuss the indications for vascular reconstruction and the
      diagnosis of peripheral arterial disease, and review of the "open" vascular
      procedures used for revascularization.

PMID- 21200283
TI  - Hyperbaric oxygen: its mechanisms and efficacy.
AB  - BACKGROUND: This article outlines therapeutic mechanisms of hyperbaric oxygen
      therapy and reviews data on its efficacy for clinical problems seen by plastic
      and reconstructive surgeons. METHODS: The information in this review was obtained
      from the peer-reviewed medical literature. RESULTS: Principal mechanisms of
      hyperbaric oxygen are based on intracellular generation of reactive species of
      oxygen and nitrogen. Reactive species are recognized to play a central role in
      cell signal transduction cascades, and the discussion will focus on these
      pathways. Systematic reviews and randomized clinical trials support clinical use
      of hyperbaric oxygen for refractory diabetic wound-healing and radiation
      injuries; treatment of compromised flaps and grafts and ischemia-reperfusion
      disorders is supported by animal studies and a small number of clinical trials,
      but further studies are warranted. CONCLUSIONS: Clinical and mechanistic data
      support use of hyperbaric oxygen for a variety of disorders. Further work is
      needed to clarify clinical utility for some disorders and to hone patient
      selection criteria to improve cost efficacy.

PMID- 21200287
TI  - Critical evaluation of endovascular surgery for limb salvage.
AB  - Rest pain, tissue loss, and gangrene are manifestations of critical limb ischemia
      caused by peripheral arterial disease and define a patient subgroup at highest
      risk for major limb amputation. Patients with nonhealing lower extremity wounds
      should be screened for the risk factors for peripheral arterial disease and
      offered noninvasive vascular testing. The diagnosis of critical limb ischemia
      mandates prompt institution of medical and surgical management to achieve the
      best chance of limb salvage. Surgical intervention has evolved from primary
      amputation to open bypass to the present era of endovascular therapy. The goals
      of surgical bypass and endovascular therapy are to improve perfusion sufficiently
      to permit healing. Despite poorer patency rates and the more frequent need for
      reintervention, endovascular therapy has been shown in multiple retrospective
      studies to achieve limb salvage similar to open bypass. Only one large,
      prospective, randomized controlled trial exists comparing open bypass with
      endovascular therapy: The Bypass versus Angioplasty in Severe Limb Ischemia of
      the Leg (BASIL) trial. Close clinical surveillance and serial monitoring of limb
      perfusion by means of noninvasive arterial studies are needed to determine the
      need for further vascular intervention. Limb salvage patients suffer from
      multiple comorbidities and benefit from a multidisciplinary, team approach to
      care.

PMID- 21200288
TI  - Discussion. Open surgical revascularization for wound healing: past performance
      and future directions; and Critical evaluation of endovascular surgery for limb
      salvage.

PMID- 21200289
TI  - Treating osteomyelitis: antibiotics and surgery.
AB  - BACKGROUND: Osteomyelitis is an inflammatory disorder of bone caused by infection
      leading to necrosis and destruction. It can affect all ages and involve any bone.
      Osteomyelitis may become chronic and cause persistent morbidity. Despite new
      imaging techniques, diagnosis can be difficult and often delayed. Because
      infection can recur years after apparent "cure," "remission" is a more
      appropriate term. METHODS: The study is a nonsystematic review of literature.
      RESULTS: Osteomyelitis usually requires some antibiotic treatment, usually
      administered systemically but sometimes supplemented by antibiotic-containing
      beads or cement. Acute hematogenous osteomyelitis can be treated with antibiotics
      alone. Chronic osteomyelitis, often accompanied by necrotic bone, usually
      requires surgical therapy. Unfortunately, evidence for optimal treatment regimens
      or therapy durations largely based upon expert opinion, case series, and animal
      models. Antimicrobial therapy is now complicated by the increasing prevalence of
      antibiotic-resistant organisms, especially methicillin-resistant Staphylococcus
      aureus. Without surgical resection of infected bone, antibiotic treatment must be
      prolonged (>=4 to 6 weeks). Advances in surgical technique have increased the
      potential for bone (and often limb) salvage and infection remission. CONCLUSIONS:
      Osteomyelitis is best managed by a multidisciplinary team. It requires accurate
      diagnosis and optimization of host defenses, appropriate anti-infective therapy,
      and often bone debridement and reconstructive surgery. The antibiotic regimen
      must target the likely (or optimally proven) causative pathogen, with few adverse
      effects and reasonable costs. The authors offer practical guidance to the medical
      and surgical aspects of treating osteomyelitis.

PMID- 21200290
TI  - Discussion. Treating osteomyelitis: antibiotics and surgery.

PMID- 21200291
TI  - Surgical treatment of osteomyelitis.
AB  - Chronic osteomyelitis is refractory to nonsurgical treatment due to a resilient,
      infective nidus that harbors sessile, matrix-protected pathogens bound to
      substrate surfaces within the wound. Curative treatment mandates physical
      (surgical) removal of the biofilm colony, adjunctive use of antibiotics to
      eliminate residual phenotypes, and efforts to optimize the host response
      throughout therapy. Patient selection, therapeutic options, and the treatment
      format are determined by the Cierny/Mader staging system, while reconstruction is
      governed by the integrity/stability of the affected bone(s) and quality/quantity
      parameters of the soft-tissue envelope.

PMID- 21200292
TI  - The new reconstructive ladder: modifications to the traditional model.
AB  - The traditional reconstructive ladder has withstood the test of time, serving as
      a thought paradigm to guide surgeons in choosing their method of wound closure
      for an assortment of defects. Advances in anatomical understanding and
      technological innovations have improved our ability to achieve definitive closure
      in a wide variety of patients. In this article, the older construct is updated to
      reflect the use of negative-pressure wound therapy and dermal matrices.
      Perforator flap concepts are also discussed in terms of their inclusion as a rung
      on the ladder.

PMID- 21200293
TI  - Discussion. The new reconstructive ladder: modifications to the traditional
      model.

PMID- 21200294
TI  - The respective roles of plastic and orthopedic surgery in limb salvage.
AB  - The evolution of techniques in plastic surgery and orthopedic surgery over the
      past few decades has enabled a great level of success in limb salvage. Limb
      salvage can now be achieved when faced with trauma, tumor, sepsis, or vascular
      disease. In fact, "What can be salvaged?" is now a less common debate among
      clinicians than "What should be salvaged?" Often discussions among surgeons from
      various subspecialties, including orthopedics, plastics, trauma, and vascular
      surgery, are characterized by how each of them can perform their respective part
      of the salvage operation, be it bony fixation, revascularization, or soft-tissue
      coverage, but none of them is certain whether it should be attempted. What is
      needed in these clinical situations is an interdisciplinary team approach led by
      individual or groups of clinicians who are familiar not only with their own
      subspecialized skills but also with those of their colleagues and the outcomes
      associated with integrated efforts at limb salvage. The concept of orthoplastic
      surgery is based on such an idea, where the combined skills and techniques of the
      orthopedic surgeon and reconstructive microsurgeon are used in concert to direct
      efforts toward limb salvage or decide against it when it is not indicated. This
      article presents a review of the roles of the two subspecialties and how an
      orthoplastic team can function with the current techniques to improve outcomes in
      limb salvage surgery.

PMID- 21200295
TI  - Role of microsurgery in lower extremity reconstruction.
AB  - Developments in reconstructive microsurgery have heralded a new phase of limb
      saving procedures. Although pedicled local fasciocutaneous or muscle flaps
      continue their useful role, microsurgical free tissue transfer is usually
      required for larger defects and also for areas without locoregional options. As
      this treatment modality has become more established, innovation and technical
      refinements have resulted in an evolution of flap surgery, including perforator
      and free-style free flaps, that has been applied to lower limb surgery. Effective
      outcome measures, bioelectronic prostheses, and composite tissue
      allotransplantation are the three major trends leading into a new era of lower
      limb reconstruction. This article outlines the role of microsurgical free tissue
      transfer for lower limb salvage and reconstruction.

PMID- 21200296
TI  - Discussion. Role of microsurgery in lower extremity reconstruction.

PMID- 21200297
TI  - Outcomes-oriented amputation surgery.
AB  - Both patients and health care professionals generally view amputation as a
      failure of modern medicine. Recent technological advances allow preservation of
      many limbs that would have required amputation in the not-too-distant past. These
      technological advances can be overused, imparting substantial potential risks to
      the patients. The goal of this article is to provide a modern outcomes-oriented
      approach to the question of limb salvage versus amputation.

PMID- 21200298
TI  - Off-loading the diabetic foot for ulcer prevention and healing.
AB  - Retrospective and prospective studies have shown that elevated plantar pressure
      is a causative factor in the development of many plantar ulcers in diabetic
      patients and that ulceration is often a precursor of lower-extremity amputation.
      Herein, we review the evidence that relieving areas of elevated plantar pressure
      (off-loading) can prevent and heal plantar ulceration.There is no consensus in
      the literature concerning the role of off-loading through footwear in the primary
      or secondary prevention of ulcers. This is likely due to the diversity of
      intervention and control conditions tested, the lack of information about off
      loading efficacy of the footwear used, and the absence of a target pressure
      threshold for off-loading. Uncomplicated plantar ulcers should heal in 6 to 8
      weeks with adequate off-loading. Total-contact casts and other nonremovable
      devices are most effective because they eliminate the problem of nonadherence to
      recommendations for using a removable device. Conventional or standard
      therapeutic footwear is not effective in ulcer healing. Recent US and European
      surveys show that there is a large discrepancy between guidelines and clinical
      practice in off-loading diabetic foot ulcers. Many clinics continue to use
      methods that are known to be ineffective or that have not been proved to be
      effective while ignoring methods that have demonstrated efficacy.A variety of
      strategies are proposed to address this situation, notably the adoption and
      implementation of recently established international guidelines, which are
      evidence based and specific, by professional societies in the United States and
      Europe. Such an approach would improve the often poor current expectations for
      healing diabetic plantar ulcers.

PMID- 21200299
TI  - Discussion: Off-loading the diabetic foot for ulcer prevention and healing.

PMID- 21200300
TI  - The role of peripheral nerve surgery in diabetic limb salvage.
AB  - BACKGROUND: Peripheral neuropathy is highly prevalent among patients with
      diabetes mellitus and demonstrates well-established consequences of limb loss
      following lower extremity ulceration, infection, and amputation and upper
      extremity loss of function. Symptomatic neuropathy is recognized by neuropathic
      pain, paresthesias, and the development of trophic limb changes. The objective of
      this review is to define the role of peripheral nerve surgery in the treatment of
      diabetic patients with upper or lower extremity symptomatic peripheral neuropathy
      and/or chronic postoperative pain. METHODS: At locations of decreased anatomical
      cross-sectional area, compression points impinge on peripheral nerve fascicles,
      and because of a synergistic effect of the metabolic derangements of diabetes,
      these points of compression are implicated in nerve abnormality and dysfunction.
      The surgical outcomes literature following decompression is reviewed, and
      specific recommendations are made for appropriate surgical candidate selection.
      In addition, the operative techniques used in peripheral nerve surgery are
      outlined. RESULTS: Peripheral nerve surgery for diabetic peripheral neuropathy is
      indicated when symptoms of pain, allodynia, or trophic changes persist despite
      optimization of medical management. Surgical treatment is considered an adjunct
      therapy to medical optimization and should be used when there is clinical and/or
      electrodiagnostic evidence of compression neuropathy or a postsurgical neuroma
      related chronic pain syndrome that is refractory to conservative management.
      CONCLUSION: Review of available reports in the surgical literature demonstrates
      that the results of peripheral nerve surgery are promising for the prevention of
      limb loss in chronic diabetes mellitus, for diminishment of pain, and for
      restoration of sensory/motor function.

PMID- 21200301
TI  - Discussion. The role of peripheral nerve surgery in diabetic limb salvage.

PMID- 21200302
TI  - Discussion. The role of peripheral nerve surgery in diabetic limb salvage.

PMID- 21200303
TI  - Venous ulcer: what is new?
AB  - The pathophysiology of venous dermal abnormality in chronic venous ulcers is
      reflective of a complex interplay that involves sustained venous hypertension,
      inflammation, changes in the microcirculation, cytokine and matrix
      metalloproteinase activation, and altered cellular function. Red blood cells and
      macromolecules extravasate into the interstitium and activate endothelial cells.
      Endothelial expression of specific adhesion molecules recruits leukocytes and
      causes diapedesis of these cells into the dermal microvasculature, promoting an
      inflammatory response with activation of cytokines and proteinases. Altered cell
      function enhances a state of vulnerability in the surrounding tissues, initiating
      specific changes associated with venous disease. Ultimately, the persistent
      inflammatory-proteinase activity leads to advanced chronic venous insufficiency
      and ulcer formation. The mainstay of therapy in venous ulcer abnormality is
      correction of the underlying venous hypertension through compression therapy
      and/or surgery. Understanding the science involved in the pathophysiology of
      venous ulcer formation has led to the development of adjunctive treatment
      directed at the dysregulated molecular pathways. Randomized clinical trials are
      critical for determining the most effective evidence-based treatments for venous
      ulcer, and this review discusses important trials that have had a significant
      impact on venous ulcer healing. In addition, the authors have included
      subsections referred to as "Translational Implications for Therapy" in the basic
      science sections of the review to help bridge the basic science knowledge with
      clinical applications that may help to modulate the molecular abnormalities in
      the pathophysiologic cascade leading to venous ulcers.

PMID- 21200304
TI  - The economics of limb salvage in diabetes.
AB  - BACKGROUND: Limb salvage requires early prevention therapy, knowledgeable use of
      wound care technology, and active management of peripheral vascular disease. This
      field has changed considerably over the past decade, with new advanced wound
      healing products and minimally invasive surgery for peripheral vascular disease.
      Treatment can be very costly in terms of medical and human resources. Evaluation
      of the clinical and economic impact of medical care is becoming more important as
      the population with diabetes and the need to contain the cost of health care
      simultaneously increase. The aim of this study was to review the economic impact
      of prevention therapies, wound care, and peripheral vascular disease
      interventions to prevent major lower extremity amputations. METHODS: The authors
      reviewed the economic impact of prevention therapy, wound care, and peripheral
      vascular disease interventions to prevent lower extremity amputations. RESULTS:
      Length of stay in the hospital and intensive care drive the cost of treatment.
      Surgical intervention and complications for foot ulcers, amputations, and
      peripheral vascular disease are significant factors in the cost of limb salvage.
      CONCLUSIONS: Not surprisingly, prevention and evidenced-based treatments are the
      most cost-effective way of reducing the use of medical resources and improving
      and prolonging productive lifestyles. Future prospective studies need to be
      conducted to more accurately understand the financial impact of limb salvage.

PMID- 21200305
TI  - Discussion. The economics of limb salvage in diabetes.

PMID- 21200306
TI  - Perioperative ischemic injury and fibrotic degeneration of muscle in a forearm
      allograft: functional follow-up at 32 months post transplantation.
AB  - Allografts of the forearm are still uncommon in the field of composite tissue
      allograft transplantation. In November 2007, a right-hand allograft and a left
      hand/full-length forearm allograft were transplanted in a 30-year-old man who
      lost both hands and the vision in his left eye due to an explosion. The patient
      underwent alemtuzumab and steroid induction therapy. Tacrolimus, mycophenolate
      mofetil, and low doses of steroids were given to prevent rejection. The
      allografts were rejected 3 times, but these episodes were controlled
      successfully. The immunosuppressive regimen was switched from tacrolimus to
      sirolimus because of increased serum creatinine. The left allograft showed a
      flexion contracture due to muscle fibrosis that was conjectured to be associated
      with a perioperative ischemic injury and permitted only a Moberg-type key pinch.
      In contrast, an excellent grade of function was observed in the right allograft.
      The Disabilities of the Shoulder, Arm, and Hand score improved from 70.83 to 36.6
      and intrinsic musculature returned to both allografts. The patient was able to
      work 2 years after transplantation. This is the first report of an ischemic
      injury related to the successful allotransplantation of a composite tissue.

PMID- 21200307
TI  - Resurfacing of lower face scars with a pre-expanded flap from the neck.
AB  - Postburn scars of the lower face often cause serious deformities and dysfunction.
      Conventional methods including skin grafts and free flaps always lead to
      unsatisfactory outcomes. In this article, we describe a series of 8 patients with
      scars of the lower face treated with an expanded neck flap. Tissue expanders were
      implanted into the neck and inflated for 3 to 5 months. The expanded flap was
      then advanced cephalically to resurface the scars of the lower face. The mean
      follow-up period was 13 months. All 8 flaps survived well except 2 patients
      developed slight necrosis at the distal edge. The flaps were well matched to the
      surrounding skin with respect to color, texture, and thickness. The cervicomental
      angle appears normal. The range of mouth opening increased. In patients with
      lower face scars and a sufficient unharmed neck flap, use of a pre-expanded neck
      flap was suitable.

PMID- 21200308
TI  - Adipose-derived stem cells for wound healing applications.
AB  - Nonhealing wounds remain a significant challenge for plastic surgeons. More than
      600,000 people suffer from venous ulcers and 1.5 to 3 million people are being
      treated for pressure sores every year in the United States. The use of tissue
      engineering techniques such as stem-cell therapy and gene therapy to improve
      wound healing is a promising strategy. Adipose tissue represents a source of
      cells that may be able to enhance wound healing. Adipose-derived stem cells
      (ASCs) are adult stem cells that are easily harvested and of great interest for
      plastic surgeons. Specifically, ASCs secrete angiogenic growth factors that can
      induce tissue regeneration. This review describes innovative research strategies
      using ASCs therapies for treatment of chronic, nonhealing wounds.

PMID- 21200309
TI  - The superior lateral genicular artery flap for soft-tissue reconstruction around
      the knee: clinical experience and review of the literature.
AB  - Soft-tissue reconstruction in the knee area needs thin, pliable, and tough skin.
      The availability of local soft tissue, which would meet the requirements best, is
      limited. This study is a retrospective analysis of our clinical experience with
      the superior lateral genicular artery (SLGA) flap for soft-tissue reconstruction
      around the knee, and a review of the relevant literature. Between 2000 and 2002,
      6 SLGA flaps were elevated for reconstruction of defects around the knee in our
      institution. Indications for the SLGA flap were chronic ulcers after bursectomy
      of the prepatellar bursa, a pressure ulcer over the patella, and a defect after
      resection of a malignant fibrous histiocytoma on the anterolateral aspect of the
      distal thigh. There was no flap loss in any of our 6 patients. Three patients had
      partial tissue loss at the distal tip of the flap. Two of the 3 resulting wounds
      were effectively covered with split skin graft, the third one eventually healed
      with wound care. Primary donor site closure was possible in all cases. There were
      no late complications, either in the flap area or in the donor site region. We
      conclude that the SLGA flap is a good option for defect coverage around the knee,
      because of its fast and easy harvest and the very good aesthetic results.

PMID- 21200310
TI  - Approach to venous thromboembolism prophylaxis: are we evolving fast enough in
      plastic surgery?
AB  - Venous thromboembolism has become a target for research by the American Society
      of Plastic Surgery. The current article reviews the steps that plastic surgeons
      and the American Society of Plastic Surgery have taken for creating guidelines in
      our field. We summarized the current reported incidences of venous
      thromboembolism in various plastic surgical procedures, and reviewed the current
      efforts that the society is taking to address the burden of this deadly
      preventable disease.

PMID- 21200311
TI  - Prevention of venous thromboembolism in body contouring surgery: a national
      survey of 596 ASPS surgeons.
AB  - INTRODUCTION: Venous thromboembolism (VTE) has been identified as a major public
      health issue. Postbariatric body contouring surgery represents a major challenge
      for VTE prophylaxis due to the presence of multiple risk factors and broad areas
      of dissection that potentially increase the risk of postoperative bleeding. AIM:
      To define current VTE prophylaxis practices among surgeons of the American
      Society of Plastic Surgeons, performing postbariatric body contouring surgery in
      the United States. MATERIAL AND METHODS: A total of 4081 surveys were sent to
      registered members of the American Society of Plastic Surgeons by e-mail. We
      received 596 (14.6%) responses. RESULTS: A total of 596 surgeons returned
      completed surveys, with 83% of respondents in private practice and 17% in
      academic practice. Deep venous thrombosis (DVT) was reported by 40% surgeons,
      pulmonary embolism (PE) by 34%, and 7% had at least 1 patient having died of a
      postoperative PE. About 39% to 48% participant surgeons reported providing no
      chemoprophylaxis to their postbariatric body contouring patients. The most common
      reason for not using routine prophylaxis was the concern for bleeding (84%),
      followed by lack of evidence specific to plastic surgery practice (50%). Academic
      surgeons were more likely to provide chemoprophylaxis when compared with those in
      nonacademic practice (P < 0.05). CONCLUSION: For postbariatric body contouring
      surgery, DVT has occurred in over one-third of plastic surgeons' practices with
      7% of surgeons reporting a patient death from PE. A substantial proportion of
      surgeons performing postbariatric body contouring are not using chemoprophylaxis
      due to bleeding risk and perceived lack of evidence. VTE prophylaxis in
      postbariatric body contouring remains a topic that deserves further study.

PMID- 21200312
TI  - Proboscis lateralis-like appendage: description of a new facial anomaly.
AB  - Proboscis lateralis is a rare craniofacial anomaly characterized by a trunk-like
      process attached to the medial portion of the orbital roof on the affected side.
      We report a case, which, though resembling proboscis lateralis in some ways, has
      certain unique features. This case had an appendage arising from the right malar
      region with a central tract lined by stratified squamous epithelium. It had
      erectile properties and was communicating with an enlarged ipsilateral maxillary
      sinus. Because of these characteristic features it appears to be a new, as yet
      unreported, facial anomaly.

PMID- 21200313
TI  - An ideal method for pressure sore reconstruction: a freestyle perforator-based
      flap.
AB  - BACKGROUND: Pressure sore reconstruction is quite difficult for plastic surgeons
      because of long-term high recurrence rates. We designed a freestyle perforator
      based flap for pressure sore reconstruction considering pressure sore recurrence
      and further reconstruction. METHODS: We used a handheld Doppler device to locate
      a perforator position just adjacent to the pressure ulcer. In a series of 34
      patients, we used 37 perforator-based flaps to reconstruct 25 sacral, 5 ischial,
      and 4 trochanteric ulcers. RESULTS: Twenty-eight of 37 flaps healed uneventfully
      without complication. One patient had a flap that totally necrosed, 3 had partial
      flap necrosis, 3 had wound dehiscence, 1 died 3 days postoperatively, and
      recurrence developed in 1 patient. CONCLUSIONS: We used the freestyle perforator
      based fasciocutaneous flap for pressure sore management with good success. These
      flaps are easy to design and provide good versatility for coverage. Cooperation
      of surgical skills and good postoperative care also contributed to the lower
      recurrence rates and satisfactory results.

PMID- 21200314
TI  - Targeted therapies and thyroid cancer: an update.
AB  - The treatment of metastatic, progressive thyroid cancer has evolved over recent
      years. New 'targeted' therapeutic approaches have been developed along with
      advances in the knowledge of thyroid carcinogenesis and the identification of
      tumor and endothelial targets. In recent years, results of targeted therapies
      have shown some benefit in refractory, progressive, differentiated, and medullary
      thyroid carcinomas but not, until recently, in undifferentiated thyroid
      carcinoma. We review here the different targeted therapies tested in thyroid
      cancers.

PMID- 21200315
TI  - Antiproteasomal agents in rectal cancer.
AB  - Colorectal cancer (CRC) is a prevalent and highly morbid condition. An improved
      understanding of the molecular pathogenesis of CRC in recent years has led to
      novel therapies complementing traditional chemotherapy, radiotherapy, and
      surgery. As in other cancers, it has become clear that the ubiquitin-proteasome
      system represents important cellular machinery that plays a complex role in the
      carcinogenesis of CRC, and may be a promising target for modulation in the
      treatment of CRC. In particular, there has been promise in targeting nuclear
      factor-kappaB and cell-cycle pathways in CRC through proteasome inhibition.
      Proteasome inhibition may be an important means of sensitizing cancers to
      traditional chemotherapy and radiotherapy through these pathways. In this review,
      we outline the basic science of the ubiquitin-proteasome system in CRC
      pathogenesis, highlight the use of proteasome inhibitors in cancers other than
      CRCs, and weigh the accumulating evidence and data, both preclinical and
      clinical, for the use of proteasome inhibition in CRC. Furthermore, we review the
      emerging evidence of proteasome inhibition as a possible radiosensitizing agent
      in rectal cancer and elucidate some possible future directions for this novel
      therapeutic option.

PMID- 21200316
TI  - Validation of the Medisana MTP Plus upper arm blood pressure monitor, for self
      measurement, according to the European Society of Hypertension International
      Protocol revision 2010.
AB  - OBJECTIVES: Standard validation protocols are objective guides for healthcare
      providers, physicians, and patients. The purpose of this study was to test
      validation of the Medisana MTP Plus upper arm blood pressure (BP) measuring
      monitor for self-measurement according to the European Society of Hypertension
      International Protocol (ESH-IP2) in adults. METHODS: The Medisana MTP Plus
      monitor is an automated and oscillometric upper arm device for home BP
      monitoring. Nine consecutive measurements were made according to the ESH-IP2.
      Overseen by an independent supervisor, measurements were recorded by two
      observers blinded from both each other's readings and from the device readings.
      RESULTS: The Medisana MTP Plus device fulfills the validation criteria of the ESH
      IP2 for the general population. The mean (standard deviation) of the difference
      between the observers and the device measurements was 0.6 mmHg (5.1 mmHg) for
      systolic and 2.7 mmHg (3.4 mmHg) for diastolic pressures, respectively.
      CONCLUSION: As the Medisana MTP Plus device has achieved the required standards,
      it is recommended for home BP monitoring in an adult population.

PMID- 21200317
TI  - Pseudotail as a feature of microphthalmia with linear skin defects syndrome.

PMID- 21200318
TI  - Unrecognized myocardial scars detected by delayed-enhanced MRI are associated
      with increased levels of NT-proBNP.
AB  - OBJECTIVES: Patients with unrecognized myocardial infarction (UMI) scars detected
      by delayed-enhanced magnetic resonance imaging (DE-MRI) have a decreased left
      ventricular ejection fraction and an increased left ventricular mass. N-terminal
      pro-brain natriuretic peptide (NT-proBNP) is a marker of heart failure, and
      troponin I (TnI) is a marker of myocardial injury. The primary aim of this study
      was to investigate whether NT-proBNP plasma levels (in addition to ejection
      fraction) differed in patients with UMI scars compared with normal participants.
      The second aim was to compare whether the TnI levels differed in those two
      groups. METHODS: Data from the Prospective Investigation of Vasculature in
      Uppsala Seniors study were used. The participants who had undergone cardiac MRI
      were included in this study (n=248). Patients were divided into three groups
      depending on the existence of a myocardial infarction (MI) scar in DE-MRI and
      their earlier history of MI. In all the patients, a peripheral blood sample was
      collected and the plasma levels of NT-proBNP and TnI were determined. RESULTS:
      Patients with UMI had higher plasma levels of NT-proBNP (median 140.2 ng/l; 25th
      75th percentiles: 79-225.5) than no-MI participants (median 94.9 ng/l; 25th-75th
      percentiles: 59.2-144.2; P=0.01) and lower levels than patients with recognized
      MI (median 310.4 ng/l; 25th-75th percentiles: 122.6-446.5; P=0.02). Plasma TnI
      values did not differ among the three groups. CONCLUSION: Patients with UMI scars
      detected by DE-MRI have increased plasma levels of NT-proBNP that is known to
      correlate with an increased risk of future cardiovascular adverse events.

PMID- 21200320
TI  - Heparin-binding protein: a diagnostic marker of acute bacterial meningitis.
AB  - BACKGROUND: The early detection of bacterial meningitis is crucial for successful
      outcome. Heparin-binding protein, a potent inducer of increased vascular
      permeability, is released from activated neutrophils in severe sepsis. OBJECTIVE:
      In this study we investigated whether heparin-binding protein levels in
      cerebrospinal fluid could be used as a diagnostic marker for acute bacterial
      meningitis. DESIGN: One prospective and one retrospective patient cohort from two
      university hospitals in Sweden were analyzed. SETTING AND PATIENTS: Cerebrospinal
      fluid samples were collected from 174 patients with suspected central nervous
      system infection. Thirty-seven patients with acute community-acquired bacterial
      meningitis, four patients with neurosurgical bacterial meningitis, 29 patients
      with viral meningitis or encephalitis, seven patients with neuroborreliosis, and
      97 control patients were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Cerebrospinal fluid samples were analyzed for the concentrations of
      heparin-binding protein, lactate, protein, glucose, neutrophils, and mononuclear
      cells. Heparin-binding protein levels were significantly higher (p < .01) in
      patients with acute bacterial meningitis (median 376 ng/mL, range 12-858 ng/mL)
      than in patients with viral central nervous system infection (median 4.7 ng/mL,
      range 3.0-41 ng/mL) or neuroborreliosis (median 3.6 ng/mL, range 3.2-10 ng/mL) or
      in control patients with a normal cerebrospinal fluid cell count (median 3.5
      ng/mL, range 2.4-8.7 ng/mL). In the prospectively studied group, a heparin
      binding protein concentration exceeding 20 ng/mL gave a sensitivity of 100%, a
      specificity of 99.2%, and positive and negative predictive values of 96.2% and
      100%, respectively, in diagnosing acute bacterial meningitis. The area under the
      receiver-operating characteristic curve for heparin-binding protein was 0.994,
      which was higher than for the other investigated parameters. CONCLUSION: Elevated
      cerebrospinal fluid levels of heparin-binding protein distinguish between
      patients with acute bacterial meningitis and patients with other central nervous
      system infections.

PMID- 21200319
TI  - A novel antimicrobial and antithrombotic lock solution for hemodialysis
      catheters: a multi-center, controlled, randomized trial.
AB  - BACKGROUND AND PURPOSE: Catheter-related bloodstream infection is the greatest
      threat to the safety of patients on hemodialysis. Catheter lock solutions
      containing heparin have been linked to an increased risk of hemorrhage and
      thrombocytopenia. OBJECTIVES: To ascertain the safety and efficacy for prevention
      of catheter-related bloodstream infection and catheter loss from patency failure
      of a novel catheter lock solution with antimicrobial and antithrombotic activity
      containing 0.24 M (7.0%) sodium citrate, 0.15% methylene blue, 0.15%
      methylparaben, and 0.015% propylparaben (C-MB-P), compared with heparin. DESIGN:
      Multicenter, prospective, randomized, open-label trial with patients studied for
      up to 6 months. An independent clinical evaluation committee assessing trial
      outcomes was blinded to patients' treatment assignments. SETTING: Twenty-five
      outpatient hemodialysis units. PATIENTS: Patients with end-stage renal disease
      receiving maintenance hemodialysis through a percutaneous cuffed and tunneled
      internal jugular hemodialysis catheters. INTERVENTIONS: Participants' catheters
      were locked between hemodialysis sessions with the C-MB-P lock solution or
      sterile saline containing 5000 units of unfractionated heparin (control).
      MEASUREMENTS AND MAIN RESULTS: We recorded and evaluated catheter-related
      bloodstream infections, catheter loss attributable to luminal thrombosis, and
      adverse events. A total of 407 patients participated in the trial (49,565
      catheter days), 201 in the C-MB-P group and 206 in the heparin group. Patients in
      the two lock solution groups were comparable for risk factors predisposing to
      catheter-related bloodstream infection. Catheters locked with C-MB-P were
      significantly less likely to cause catheter-related bloodstream infection (0.24
      vs. 0.82 per 1000 catheter days; relative risk, 0.29; 95% confidence interval,
      0.12-0.70; p = .005) and were less likely to be lost because of patency failure
      (0 vs. 4; log rank, p = .04). CONCLUSIONS: The novel C-MB-P lock solution is well
      tolerated, significantly reduces the risk of catheter-related bloodstream
      infection, and provides protection comparable to heparin against patency failure.

PMID- 21200321
TI  - Hydrogen-rich saline reduces delayed neurologic sequelae in experimental carbon
      monoxide toxicity.
AB  - OBJECTIVE: We investigated the feasibility and efficacy of hydrogen-rich saline
      therapy on delayed neurologic sequelae in a rat model of severe acute carbon
      monoxide (CO) poisoning. DESIGN: Controlled animal study. SETTING: University
      research laboratory for Diving Medicine. SUBJECTS: Sprague-Dawley rats weighing
      250 +/- 20 g. INTERVENTIONS: The rats were exposed to 1000 ppm CO in air for 40
      min and then to 3000 ppm for another 20 min until they lost consciousness. Rats
      were intraperitoneal injected with hydrogen-rich saline or normal saline (10
      mL/kg) for six times after resuscitation at 0, 12, 24, 36, 48, and 60 hrs,
      respectively. The rats without CO poisoning were used as normal controls.
      MEASUREMENTS AND MAIN RESULTS: Brain tissue inflammation, cell death, and
      cognitive dysfunction were observed at one week after CO poisoning. Hydrogen-rich
      saline treatment significantly reduced the level of degraded myelin basic
      protein, decreased the expression of ionized calcium-binding adapter molecule 1,
      Iba1, a microglial marker, reduced DNA oxidation, and suppressed proinflammatory
      cytokine interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in the
      cortex and hippocampal tissues when compared with those in normal saline-treated
      rats. These histologic and biological improvements were accompanied with an
      improvement in the Morris water maze test. CONCLUSIONS: This observation
      demonstrated that hydrogen-rich saline peritoneal injection improves histologic
      and functional assessment in a rat model of CO encephalopathy. Hydrogen saline
      has potentials as a novel and alternative therapy for severely CO-poisoned
      patients with delayed neurologic sequelae. The therapeutic effects of hydrogen
      rich saline may be related to antioxidant and anti-inflammatory actions.

PMID- 21200322
TI  - Deletion of peroxiredoxin 6 potentiates lipopolysaccharide-induced acute lung
      injury in mice.
AB  - OBJECTIVE: To investigate the role and signaling pathway of peroxiredoxin 6, a
      newly identified peroxidase, in lipopolysaccharide-induced acute lung injury.
      DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratory.
      SUBJECTS: Peroxiredoxin 6 (-/-) and wild-type C57BL/6 mice. INTERVENTIONS: Wild
      type or peroxiredoxin 6 (-/-) mice were challenged by intratracheal instillation
      of lipopolysaccharide (5 mg/kg) for 4 hrs or 24 hrs for lung injury measurement.
      In other studies, peritoneal macrophages, isolated from wild-type and
      peroxiredoxin 6 (-/-) mice, were preincubated in presence or absence of mitogen
      activated protein kinases inhibitors for 30 mins before being stimulated with
      lipopolysaccharide (1 MUg/mL) for 4 hrs. MEASUREMENTS AND MAIN RESULTS:
      Bronchoalveolar lavage myeloperoxidase activity and the lung injury score were
      significantly increased in peroxiredoxin 6 (-/-) mice compared with wild-type
      mice after lipopolysaccharide instillation at both 4 hrs and 24 hrs. Hydrogen
      peroxide and malondialdehyde levels, as well as nuclear factor-kappaB activities,
      tumor necrosis factor-alpha, interleukin-1beta, and matrix metalloproteinase-9
      messenger RNA, protein concentration, and activities were significantly increased
      whereas total antioxidative capability was markedly decreased in lungs of
      peroxiredoxin 6 (-/-) mice compared with wild-type mice. In vitro studies showed
      intracellular reactive oxygen species levels and release of tumor necrosis factor
      alpha, interleukin-1, and matrix metalloproteinase-9 were significantly increased
      in macrophages from peroxiredoxin 6 (-/-) mice compared with that from wild-type
      mice after lipopolysaccharide stimulation. Cytokines release was partially
      suppressed by extracellular signal-regulated kinase and c-Jun N-terminal kinase
      inhibitors, but not by the p38 mitogen-activated protein kinase inhibitor.
      CONCLUSIONS: Deletion of peroxiredoxin 6 exaggerates lipopolysaccharide-induced
      acute lung injury and inflammation with increased oxidative stress, inflammatory
      responses, and matrix degradation, all of which were partially dependent on
      nuclear factor-kappaB, extracellular signal-regulated kinase, and c-Jun N
      terminal kinase pathways.

PMID- 21200323
TI  - Modern applications of ureteroscopy for intrarenal stone disease.
AB  - PURPOSE OF REVIEW: Ureteroscopy continues to improve as a method for management
      of intrarenal stone disease. The development of new technologies and enhanced
      application of existing therapies is expanding the indications of ureteroscopy
      for the management of renal calculi. RECENT FINDINGS: Improvements in image
      quality have been achieved with the adoption of digital ureteroscopes.
      Modifications of standard ureteroscopic techniques and improvements in surgical
      skill training are also being made. Ureteroscopy is demonstrated to be well
      tolerated and efficacious for the management of intrarenal calculi in multiple
      patient populations and is also cost-efficient. SUMMARY: The indications for
      ureteroscopic management of renal calculi are expanding, and this technique is
      quickly being adopted as a routine option for the management of intrarenal stone
      disease.

PMID- 21200324
TI  - Robotic surgery and minimally invasive management of renal tumors with vena caval
      extension.
AB  - PURPOSE OF REVIEW: Although laparoscopic nephrectomy for renal cell carcinoma
      (RCC) has become a widely accepted option for most renal tumors, open surgery
      remains the standard in managing tumors with extension into the inferior vena
      cava (IVC). Robotic technology has been applied to increasingly complex
      laparoscopic procedures and may facilitate minimally invasive procedures
      previously felt unfeasible with standard laparoscopy. The evolution to completely
      intracorporeal techniques for IVC tumor thrombectomy from incremental
      advancements in laparoscopic and hybrid techniques is reviewed. RECENT FINDINGS:
      Laparoscopic management of IVC tumor thrombi has been demonstrated in animal
      models and more recently in the form of individual case reports. Hybrid
      laparoscopic techniques have been developed to allow hand-assisted thrombus
      retraction out of the IVC or open incisions for IVC management after laparoscopic
      dissection. Robotic surgery only recently has been described to allow a
      completely minimally invasive technique for tumor thrombectomy even when cross
      clamping of the cava is required. Such techniques have yet to gain popular
      acceptance but have been reproduced to a limited degree by other investigators.
      SUMMARY: Robotic technology applied to complex laparoscopic procedures may extend
      the limits of what can be performed successfully in minimally invasive fashion.
      The early reported experiences of robotic nephrectomy with IVC tumor
      thrombectomy, thus far, demonstrate feasibility but require further
      investigation. Discrimination of ideal candidates and reproducibility by other
      surgeons will be necessary before widespread adoption and acceptance.

PMID- 21200325
TI  - Profile of protein expression of the colon cancer cell line SW480 with
      survivin/shRNA.
AB  - Survivin has attracted abundant interest in tumor research since it was
      discovered in 1997. However, several studies indicate that the relationship
      between survivin expression and tumor behavior is still not fully understood.
      Among the current methods available, proteomics is an effective platform to
      globally detect and characterize proteins. Thus, we constructed the recombinant
      adenovirus [ad-survivin/ short hairpin RNA (shRNA)], which contains shRNA of
      survivin, and transfected it into SW480 cells. Then, we detected survivin gene
      expression after shRNA interference, and its influence on apoptosis and the cell
      cycle was analyzed. A comparative proteomic approach was used to identify the
      differential proteins between SW480/survivin (-) and SW480/survivin (+) cells.
      The results showed that survivin was expressed at a high level in SW480 cells and
      that the subcellular localization was observed in the cytoplasm. Recombinant
      adenovirus could suppress survivin-expression efficiency and induce apoptosis by
      affecting mitosis. The differentially expressed proteins identified by two
      dimensional proteome analysis were related to various cellular programs involving
      cell proliferation, cell cycle, apoptosis, expression of nucleic acid metabolic
      genes, and the regulation of signal transduction. The proteomic approach
      implemented here offers a powerful tool for identifying novel tumor markers.
      Survivin plays an important role in controlling tumor growth by a variety of
      molecular regulatory mechanisms. Inhibition of survivin expression could
      effectively inhibit tumor growth.

PMID- 21200326
TI  - Effects of cilostazol in the heart.
AB  - Cilostazol is a selective phosphodiesterase 3 (PDE3) inhibitor approved by the
      Food and Drug Administration for treatment of intermittent claudication. It has
      also been used in bradyarrhythmic patients to increase heart rates. Recently,
      cilostazol has been shown to prevent ventricular fibrillation in patients with
      Brugada syndrome. Cilostazol is hypothesized to suppress transient outward
      potassium (Ito) current and increase inward calcium current, thus, maintaining
      the dome (phase 2) of action potential, decreasing transmural dispersion of
      repolarization and preventing ventricular fibrillation. Although many PDE3
      inhibitors have been shown to increase cardiac arrhythmia in heart failure,
      cilostazol has presented effects that are different from other PDE3 inhibitors,
      especially adenosine uptake inhibition. Owing to this effect, cilostazol could be
      an effective cardioprotective drug, with its beneficial effects in preventing
      arrhythmia. In this review, the cardiac electrophysiological effects of
      cilostazol are presented and its possible cardioprotective effects, particularly
      in preventing ventricular fibrillation, are discussed, with emphasis on the need
      to further verify its clinical benefits.

PMID- 21200327
TI  - The impact of coronary artery bypass graft surgery on depression and anxiety.
AB  - AIMS: Psychiatric disorders, including depression and anxiety, after coronary
      artery bypass graft (CABG) surgery are rife. Such disorders can make important
      impacts on patients. We aimed to evaluate the value of the surgical approach,
      associated with other medical therapies in decreasing depression and anxiety in a
      group of patients scheduled for CABG in our center. METHODS: In a prospective
      study, all patients scheduled for CABG in a 6-month period were selected
      consecutively to enter a two-stage study. The patients were interviewed using
      Hamilton Depression and Anxiety Rating Scales before and 4 weeks after the
      operations. RESULTS: Mean age of men in the anxiety group (68 patients) was
      significantly lower than that of women. Mean anxiety scores before and after the
      operations were 8.9 +/- 4.7 and 6.7 +/- 4.4, respectively (P = 0.026). Mean age
      of women in the depression group (55 patients) was more than that of men (P =
      0.04). Mean scores of depression before and after the operations were 13.30 +/-
      7.59 and 11.2 +/- 7.19, respectively (P = 0.027). Men's scores of anxiety and
      depression were decreased significantly more than those in women after
      operations. CONCLUSION: CABG surgery can decrease the level of anxiety and
      depression in patients scheduled for surgery in a short-term follow-up. This
      effect is more prominent in men than women.

PMID- 21200328
TI  - Serial pediatric symptom checklist screening in children with prenatal drug
      exposure.
AB  - OBJECTIVE: To examine screening results obtained by serial annual behavioral
      assessment of children with prenatal drug exposure. METHOD: The Maternal
      Lifestyle Study enrolled children with prenatal cocaine exposure (PCE) at birth
      for longitudinal assessments of developmental, behavioral, and health outcomes.
      At 8, 9, 10, 11, and 12 years of age, caregivers rated participants on the
      Pediatric Symptom Checklist (PSC). Serial PSC results were compared with an
      established broad-based behavioral measure at 9, 11, and 13 years. PSC results
      were analyzed for 1081 children who had at least 2 annual screens during the 5
      year time span. Most subjects (87%) had 4 or more annual screens rated by the
      same caregiver (80%). PSC scores (and Positive screens) over time were compared
      at different time points for those with and without PCE. Covariates, including
      demographic factors and exposures to certain other substances, were controlled.
      RESULTS: Children with PCE had significantly higher scores overall, with more
      Positive screens for behavior problems than children without PCE. Children with
      PCE had more externalizing behavior problems. Children exposed to tobacco
      prenatally and postnatally also showed higher PSC scores. Over time, PSC scores
      differed slightly from the 8-year scores, without clear directional trend.
      Earlier PSC results predicted later behavioral outcomes. CONCLUSION: Findings of
      increased total PSC scores and Positive PSC screens for behavioral concerns in
      this group of children with prenatal substance exposure support the growing body
      of evidence that additional attention to identification of mental health problems
      may be warranted in this high-risk group.

PMID- 21200329
TI  - Infant temperament and high-risk environment relate to behavior problems and
      language in toddlers.
AB  - OBJECTIVE: This study examined the role that easy infant temperament and
      cumulative environmental risk play in predicting cognitive, language, and
      behavioral outcomes in 3-year-old children at high social risk. METHODS: Subjects
      were 412 mother-infant dyads, recruited at birth, participating in a longitudinal
      study examining the effects of prenatal methamphetamine on child development.
      This analysis includes a subsample (n = 290) of the study with a completed 3-year
      visit. Temperament was assessed by the Infant Behavior Questionnaire at 12
      months. Factor analysis from well-validated measures generated "easy" and
      "difficult" temperament profiles and a profile for high-risk environment.
      Caretaker receptive vocabulary served as a proxy for intelligence quotient.
      Outcomes at 3 years included motor and mental development, behavior problems, and
      language. Linear regression and hierarchical linear modeling examined the effects
      of temperament, high-risk environment, and caregiver receptive language on
      outcomes adjusting for maternal drug use and demographic and socioeconomic
      covariates. RESULTS: Internalizing and externalizing behaviors were lower in
      children with easy temperament and higher with increased environmental risk. Easy
      temperament attenuated behavioral problems only in the setting of lower
      environmental risk. Caregiver receptive language was associated with lower
      internalizing scores. High-risk environment and temperament factors were not
      related to cognitive or motor outcomes. Prenatal methamphetamine exposure was not
      associated with 3-year-old outcomes, nor did it alter the protective effects of
      an easier temperament on child behavior. CONCLUSIONS: CHILDREN growing up in
      adverse social environments had increased behavioral problems and compromised
      language development. Conversely, an easy temperament acts as a protective factor
      for social-emotional development and could be related to resilience.

PMID- 21200330
TI  - Attention-deficit hyperactivity disorder in children with high intelligence
      quotient: results from a population-based study.
AB  - OBJECTIVE: To compare the characteristics of children with attention-deficit
      hyperactivity disorder (ADHD) who have high intelligence quotient (IQ) versus
      normal and low IQ through long-term follow-up of children with ADHD from a
      population-based birth cohort. METHODS: Subjects included children with research
      identified ADHD (N = 379) from a birth cohort (N = 5718). Full scale IQ scores
      obtained between ages 6 and 18 years were used to categorize children into 3
      groups: Low (IQ < 80), Normal (80 <= IQ < 120), and High IQ (IQ >= 120). Subjects
      were retrospectively followed up from birth until emigration, death, or high
      school graduation/dropout. The groups were compared on demographic
      characteristics, age at which ADHD case criteria were met, comorbidities,
      treatment, and school outcomes. RESULTS: There were no significant differences
      among children with high (N = 34), normal (N = 276), or low IQ (N = 21) and ADHD
      in numerous characteristics, including median age at which ADHD criteria were
      fulfilled (9.5, 9.7, and 9.8 years); rates of comorbid learning disorders (85.3%,
      78.3%, and 76.2%), psychiatric disorders (47.1%, 50.4%, and 47.6%), and substance
      abuse (17.6%, 23.6%, and 19.0%); and rates of stimulant treatment (79%, 75%, and
      90%). In comparison to children with normal or low IQ, those with high IQ had
      mothers with higher educational levels (e.g., college graduation rates 44.1%,
      11.6%, and 14.3%), and higher reading achievement (median national percentiles on
      standardized reading tests 77.0, 42.0, and 29.0, p < 0.001). CONCLUSIONS: These
      findings suggest that ADHD is similar among children with high, normal, and low
      IQ, although high IQ may favorably mediate some outcomes such as reading
      achievement. Diagnosis and treatment of ADHD are important for all children,
      regardless of cognitive ability.

PMID- 21200331
TI  - A psychological intervention for pediatric chest pain: development and open
      trial.
AB  - OBJECTIVE: Noncardiac chest pain (NCCP) is a common and persistent problem for
      children and adolescents; typically there is no clear medical cause. To date, no
      psychological intervention has been studied for chest pain in a pediatric sample.
      METHODS: (a) We developed a brief psychological treatment for chest pain and
      associated worry in children and adolescents with NCCP. This program includes
      psychoeducation, breathing retraining, cognitive coping strategies, and 1 session
      of parent education and coaching regarding the impact of reinforcement on pain
      and coping behaviors. (b) We treated 9 youngsters with chronic NCCP, assessing
      pain, somatization, disability, anxiety and depressive symptoms, and coping.
      Assessments were conducted before, after, and 6 months following treatment.
      RESULTS: After treatment, there was a significant decrease in chest pain and
      somatization. Benefits were maintained at 6-month follow-up. There was no
      decrease in associated psychological symptoms. CONCLUSIONS: A brief psychological
      treatment for pediatric NCCP is feasible to administer and may help alleviate
      symptoms of pediatric NCCP. Further study in a randomized trial is needed.

PMID- 21200332
TI  - Lessons about neurodevelopment from anatomical magnetic resonance imaging.
AB  - The arrival of magnetic resonance imaging (MRI) has offered major advances in our
      understanding of both normal and abnormal neurodevelopment. This review is a
      broad overview of the key findings that anatomical MRI research has provided in
      regard to the normal developing brain and presents key issues and consideration
      in pediatric imaging. Volumetric MRI studies, using various methods, have
      reliably found that gray-matter volume increases and peaks in late childhood,
      followed by a slow but continued loss, whereas white matter increases rapidly
      until age 10 years with continued development well beyond adolescence. The
      introduction of analysis techniques, such as voxel-based morphometry, cortical
      thickness measures, and cortical pattern mapping, have begun to answer more
      regionally specific questions. Pediatric neuroimaging studies carry specific
      requirements, given not only the high degree of variability between individuals,
      ages, and sexes but also issues of behavioral compliance, MR signal, and
      postprocessing methodologies such as appropriate normalization. Considerations in
      future pediatric imaging studies are presented. Ultimately, the promise of
      computational analysis of structural MRI data is to understand how changes in
      cerebral morphology relate to acquisition and enhancement of skills and behaviors
      in typical and atypical development.

PMID- 21200333
TI  - Early erythropoietin therapy attenuates remodeling and preserves function of left
      ventricle in porcine myocardial infarction.
AB  - Erythropoietin (EPO) has been shown to have anti-inflammatory, antiapoptotic, and
      proangiogenic effects. This study investigated whether early EPO treatment
      effectively preserves left ventricular (LV) function in porcine acute myocardial
      infarction (AMI). Eighteen male mini-pigs divided into groups 1 (sham), 2 (AMI),
      and 3 (AMI with 2 consecutive EPO doses [7500 IU per animal each time] at 30
      minutes and 24 hours after AMI induction) underwent echocardiography before and
      14 days after AMI induction through left anterior descending artery (LAD)
      ligation with myocardium harvested for analysis. Larger infarcted areas (IA) were
      noted in group 2 than in group 3. In both IA and peri-IA, percentage of apoptotic
      nuclei and CD40-positive cells, messenger RNA expressions of IL-8, matrix
      metalloproteinase-9, caspase-3, and Bcl-2 associated x protein were highest,
      whereas proliferator-activated receptor-gamma coactivator-1alpha, endothelial
      nitric oxide synthase and Bcl-2 were lowest in group 2. Oxidative stress and
      cytosolic cytochrome c in IA were increased (P < 0.001), whereas protein
      expression of connexin43, cytochrome c, and protein kinase C-epsilon; in
      mitochondria were reduced in group 2 than in other groups (P < 0.045). The
      fibrosis in IA was notably decreased in group 3 compared with that in group 2.
      The number of small arterioles and capillary density in IA was highest in group
      3, whereas LV performance was lowest in group 2 (P < 0.045). In conclusion, the
      results demonstrated that early EPO administration in a porcine AMI model
      effectively limits infarct size, attenuates LV remodeling, and preserves LV
      function.

PMID- 21200334
TI  - Comparison of characteristics and outcomes of patients undergoing saphenous vein
      graft stenting who were or were not enrolled in the stenting of saphenous vein
      grafts randomized controlled trial.
AB  - OBJECTIVE: We sought to compare the characteristics and outcomes of patients who
      were enrolled versus those who were not enrolled in the Stenting of Saphenous
      Vein Grafts (SOS) randomized controlled trial. METHODS AND RESULTS: We identified
      all patients who underwent saphenous vein graft stenting during the SOS Trial
      enrollment period (May 2005 and October 2007) at our institution. Baseline
      characteristics and clinical outcomes were compared between patients who were
      versus those who were not enrolled in SOS. Of the 97 patients who underwent
      saphenous vein graft stenting during the study period, 62 patients (64%) were
      enrolled in SOS. In the enrolled group, 62 patients with 91 lesions were
      randomized to a bare metal stent (BMS) (n = 39) or paclitaxel-eluting stent (n =
      41). In the nonenrolled group, 35 patients with 44 lesions received a drug
      eluting stent (DES) (n = 27) or BMS (n = 8). During a median follow-up period of
      2.66 years, nonenrolled patients had higher mortality (31.4% vs 14.5%, P =
      0.039), but lower rates of myocardial infarction (5.7% vs 32.3%, P = 0.005) and
      target vessel failure (37% vs 61.3%, P = 0.023). Overall, patients who received
      DES had lower incidence of myocardial infarction, target lesion
      revascularization, target vessel failure and major adverse cardiac events, and
      similar mortality compared with the BMS group. CONCLUSIONS: Compared with
      nonenrolled patients, those who were enrolled in SOS had lower mortality.
      Patients receiving DES had better outcomes than those receiving BMS in both
      groups.

PMID- 21200335
TI  - Assessment of atrial conduction time in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disorder
      resulting in multisystemic inflammatory damage. Recent articles report that 20%
      to 30% of deaths in patients with SLE have cardiovascular origin. The aim of this
      study was to investigate the atrial conduction time in patients with SLE by using
      high-usefulness tissue Doppler echocardiography (TDI). METHODS: The study
      population included 56 patients with SLE (49 women; mean [SD] age, 46.2 [12.2]
      years, and mean [SD] disease duration, 30.7 [10.9] months) and 45 healthy
      subjects as control group (39 women; mean [SD] age, 45.8 [12.3] years). P-wave
      dispersion (PWD) was calculated by using 12-lead electrocardiogram. The timing of
      atrial contractions (PA) was measured as the interval between the onset of P wave
      on electrocardiogram and the beginning of A wave on TDI. Atrial electromechanical
      delay (EMD) was calculated from the lateral (PA lateral), septal (PA septal)
      mitral annulus, and lateral tricuspid annulus (PA tricuspid). RESULTS: Lateral
      mitral annulus and PA septal were significantly longer in the patients with SLE
      than in the control subjects (66.7 [15.9] vs 56.5 [13.7], P = 0.001, and 53.5
      [15.0] vs 45.0 [15.1] milliseconds, P = 0.006, respectively). Interatrial (PA
      lateral - PA tricuspid) and intra-atrial (PA septal - PA tricuspid) EMD were
      significantly higher in SLE groups (25.5 [9.7] vs 19.9 [8.3], P = 0.003 and 13.3
      [7.7] vs 8.4 [8.0] milliseconds, P = 0.002, respectively). Similarly, maximum P
      wave duration and PWD were significantly longer in the patients with SLE than in
      the control subjects (104.9 [13.5] vs 98.1 [15.1], P = 0.021 and 24.6 [7.4] vs
      20.0 [8.1] milliseconds, P = 0.004, respectively). There were significant
      positive correlations between the disease duration and interatrial EMD (r =
      0.611, P < 0.001) and intra-atrial EMD (r = 0.565, P < 0.001). Positive
      correlation was also present between the disease duration and PWD (r = 0.457, P <
      0.001). CONCLUSION: Atrial EMD is prolonged in patients with SLE. We have also
      shown that PWD, intra-atrial EMD, and interatrial EMD were significantly
      correlated with disease duration. This study calls attention to the following:
      the measurement of atrial conduction time may be clinically helpful in the
      definition of cardiac involvement.

PMID- 21200336
TI  - Association between physical activity and kidney function: National Health and
      Nutrition Examination Survey.
AB  - INTRODUCTION: Chronic kidney disease is a condition characterized by the
      deterioration of the kidney's ability to remove waste products from the body.
      Although treatments to slow the progression of the disease are available, chronic
      kidney disease may eventually lead to a complete loss of kidney function.
      Previous studies have shown that physical activities of moderate intensity may
      have renal benefits. Few studies have examined the effects of total movement on
      kidney function. The purpose of this study was to determine the association
      between time spent at all levels of physical activity intensity and sedentary
      behavior and kidney function. METHODS: Data were obtained from the 2003-2004 and
      2005-2006 National Health and Nutrition Examination Survey, a cross-sectional
      study of a complex, multistage probability sample of the US population. Physical
      activity was assessed using an accelerometer and questionnaire. Glomerular
      filtration rate (eGFR) was estimated using the Modification of Diet in Renal
      Disease study formula. To assess linear associations between levels of physical
      activity and sedentary behavior with log-transformed estimated GFR (eGFR), linear
      regression was used. RESULTS: In general, physical activity (light and total) was
      related to log eGFR in females and males. For females, the association between
      light and total physical activity with log eGFR was consistent regardless of
      diabetes status. For males, the association between light and total physical
      activity and log eGFR was only significant in males without diabetes.
      CONCLUSIONS: When examining the association between physical activity, measured
      objectively with an accelerometer, and kidney function, total and light physical
      activities were found to be positively associated with kidney function.

PMID- 21200337
TI  - Physical activity self-monitoring and weight loss: 6-month results of the SMART
      trial.
AB  - INTRODUCTION: Weight loss has been associated with higher physical activity (PA)
      levels and frequent dietary self-monitoring. Less is known about how PA self
      monitoring affects adherence to PA goals, PA levels, and weight change. METHODS:
      The SMART Trial is a clinical weight loss trial in which 210 overweight adults
      were randomized equally to one of three arms: 1) paper record (PR), 2) personal
      digital assistant with self-monitoring software (PDA), and 3) PDA with daily
      tailored feedback message (PDA + FB). PA self-monitoring and adherence to PA
      goals were based on entries in weekly submitted diaries. PA levels were measured
      via self-report by the past 6-month Modifiable Activity Questionnaire at baseline
      and 6 months. RESULTS: Data are presented on 189 participants with complete 6
      month PA data (84% female, 77% white, mean age = 47.3 +/- 8.8 yr, mean body mass
      index = 34.1 +/- 4.5 kg.m(-2)). Median PA level was 7.96 MET.h.wk(-1) at baseline
      and 13.4 MET.h.wk(-1) at 6 months, with significant PA increases in all three
      arms. PDA + FB arm had a higher mean number of weekly self-monitoring entries
      than the PR arm (3.4 vs 2.4, P = 0.003) and were more likely to maintain high
      (i.e., 100%) adherence to PA goals over time than the PDA (P = 0.02) or PR arms
      (P = 0.0003). Both PA self-monitoring and adherence to PA goals were related to
      higher PA levels at 6 months. A higher mean rate of PA self-monitoring was
      associated with a greater percentage of weight decrease (rho = -0.49, P < 0.0001)
      at 6 months. CONCLUSIONS: PA self-monitoring and adherence to PA goals were more
      likely in participants in the PDA + FB arm and in turn predicted higher PA levels
      and weight loss.

PMID- 21200338
TI  - Leukocyte beta2-adrenergic receptor expression in response to resistance
      exercise.
AB  - PURPOSE: Epinephrine and norepinephrine mediate interactions between the
      neuroendocrine and the immune systems to alter immune cell activity. Although
      both systems respond to exercise stress, less is known about how they interact in
      response to such stress. The purpose of this investigation was to examine beta2
      adrenergic receptor (beta2-ADR) expression on circulating leukocytes to an acute
      bout of resistance exercise in men and women. METHODS: Resistance-trained men (n
      = 8; mean +/- SD age = 24.63 +/- 5.07 yr, body mass index = 26.09 +/- 2.21 kg.m(
      2)) and women (n = 7; age = 22.13 +/- 3.09 yr, body mass index = 22.63 +/- 2.03
      kg.m(-2)) performed an acute resistance exercise protocol (six sets of five
      repetition maximum heavy squats) and a control test (i.e., identical conditions
      with no exercise) in a balanced, randomized order. Using a within-subject design,
      beta2-ADR expressions on circulating leukocytes were evaluated with flow
      cytometry, and plasma epinephrine and norepinephrine were evaluated with high
      performance liquid chromatography. RESULTS: Plasma epinephrine and norepinephrine
      increased during the exercise bout and returned to baseline during recovery.
      beta2-ADR expression on monocytes was elevated in anticipation of the exercise
      protocol. beta2-ADR expression on monocytes and granulocytes decreased during the
      exercise. beta2-ADR expression on lymphocytes was elevated during the recovery
      time points. CONCLUSIONS: In conclusion, beta2-ADR expression on leukocyte
      subpopulations changes in response to acute heavy resistance exercise protocol.
      The present findings provide insights into the potential temporal interactions
      between the neuroendocrine and the immune systems in response to the
      physiological stress of acute heavy resistance exercise in men and women.

PMID- 21200339
TI  - Intermittent-sprint performance and muscle glycogen after 30 h of sleep
      deprivation.
AB  - PURPOSE: The aim of this study was to determine the effects of 30 h of sleep
      deprivation on consecutive-day intermittent-sprint performance and muscle
      glycogen content. METHODS: Ten male, team-sport athletes performed a single-day
      "baseline" session and two consecutive-day experimental trials separated either
      by a normal night's sleep (CONT1 and CONT2) or no sleep (SDEP1 and SDEP2). Each
      session included a 30-min graded exercise run and 50-min intermittent-sprint
      exercise protocol, including a 15-m maximal sprint every minute and self-paced
      exercise bouts of varying intensities. Muscle biopsies were extracted before and
      after exercise during the baseline session and before exercise on day 2 during
      experimental trials. Voluntary force and activation of the right quadriceps, nude
      mass, HR, core temperature, capillary blood lactate and glucose, RPE, and a
      modified POMS were recorded before, after, and during the exercise protocols.
      RESULTS: Mean sprint times were slower on SDEP2 (2.78+/-0.17 s) compared with
      SDEP1 (2.70+/-0.16 s) and CONT2 (2.74+/-0.15 s, P<0.05). Distance covered during
      self-paced exercise was reduced during SDEP2 during the initial 10 min compared
      with SDEP1 and during the final 10 min compared with CONT2 (P<0.05). Muscle
      glycogen concentration was lower before exercise on SDEP2 (209+/-60 mmol.kg dry
      weight) compared with CONT2 (274+/-54 mmol.kg dry weight, P=0.05). Voluntary
      force and activation were reduced on day 2 of both conditions; however, both were
      lower in SDEP2 compared with CONT2 (P<0.05). Sleep loss did not affect RPE but
      negatively affected POMS ratings (P<0.05). CONCLUSIONS: Sleep loss and associated
      reductions in muscle glycogen and perceptual stress reduced sprint performance
      and slowed pacing strategies during intermittent-sprint exercise for male team
      sport athletes.

PMID- 21200340
TI  - Interhemispheric plasticity in humans.
AB  - INTRODUCTION: Chronic unimanual motor practice increases the motor output not
      only in the trained but also in the nonexercised homologous muscle in the
      opposite limb. We examined the hypothesis that adaptations in motor cortical
      excitability of the nontrained primary motor cortex (iM1) and in interhemispheric
      inhibition from the trained to the nontrained M1 mediate this interlimb cross
      education. METHODS: Healthy, young volunteers (n=12) performed 1000 submaximal
      voluntary contractions (MVC) of the right first dorsal interosseus (FDI) at 80%
      MVC during 20 sessions. RESULTS: Trained FDI's MVC increased 49.9%, and the
      untrained FDI's MVC increased 28.1%. Although corticospinal excitability in iM1,
      measured with transcranial magnetic stimulation (TMS) before and after every
      fifth session, increased 6% at rest, these changes, as those in intracortical
      inhibition and facilitation, did not correlate with cross education. When weak
      and strong TMS of iM1 were delivered on a background of a weak and strong muscle
      contraction, respectively, of the right FDI, excitability of iM1 increased
      dramatically after 20 sessions. Interhemispheric inhibition decreased 8.9%
      acutely within sessions and 30.9% chronically during 20 sessions and these
      chronic reductions progressively became more strongly associated with cross
      education. There were no changes in force or TMS measures in the trained group's
      left abductor minimi digiti and there were no changes in the nonexercising
      control group (n=8). CONCLUSIONS: The findings provide the first evidence for
      plasticity of interhemispheric connections to mediate cross education produced by
      a simple motor task.

PMID- 21200341
TI  - Postexercise skeletal muscle glucose transport is normal in kininogen-deficient
      rats.
AB  - A single exercise bout stimulates skeletal muscle glucose transport (GT) in the
      absence or presence of insulin. It has been suggested that the kallikrein-kinin
      system may contribute to exercise effects on both insulin-independent and insulin
      dependent GT. Plasma kininogen, a key kallikrein-kinin system component, is a
      protein substrate for the enzyme kallikrein and the source of the peptide
      bradykinin. PURPOSE: This study aimed to determine whether the postexercise (PEX)
      increase in insulin-dependent or insulin-independent GT is reduced in rats
      deficient in plasma kininogen versus normal rats. METHODS: Male Brown Norway (BN)
      and Brown Norway Katholiek (BNK; plasma kininogen-deficient) rats were studied.
      BN and BNK rats were assigned to exercise (4*30-min swim) or sedentary (SED)
      groups. Rats were anesthetized immediately (0hPEX) or 3 h (3hPEX) after exercise.
      For 0hPEX and 0hSED rats, one epitrochlearis muscle per rat was used for AMPK
      phosphorylation and muscle glycogen analyses. The contralateral muscle was
      incubated with [H]-3-O-methylglucose (3-MG) for GT assay. For 3hPEX and 3hSED
      rats, one muscle from each rat was incubated without insulin, and the
      contralateral muscle was incubated with 60 MUU.mL insulin, and both muscles were
      incubated with 3-MG for GT measurement. RESULTS: For 0hPEX versus 0hSED, both BN
      and BNK rats had greater insulin-independent GT and AMPK phosphorylation with
      reduced glycogen after exercise. No genotype effects were found 0hPEX. There was
      a significant main effect of exercise (3hPEX>3hSED) and no interaction between
      exercise and genotype for basal or insulin-stimulated GT. CONCLUSIONS: Plasma
      kininogen deficiency did not alter insulin-independent GT, AMPK phosphorylation,
      or glycogen depletion 0hPEX or insulin-dependent GT 3hPEX, suggesting that normal
      plasma kininogen is not essential for these important exercise effects.

PMID- 21200342
TI  - Inspiratory muscle training in type 2 diabetes with inspiratory muscle weakness.
AB  - PURPOSE: Patients with type 2 diabetes mellitus may present weakness of the
      inspiratory muscles. We tested the hypothesis that inspiratory muscle training
      (IMT) could improve inspiratory muscle strength, pulmonary function, functional
      capacity, and autonomic modulation in patients with type 2 diabetes and weakness
      of the inspiratory muscles. METHODS: Maximal inspiratory muscle pressure (PImax)
      was evaluated in a sample of 148 patients with type 2 diabetes. Of these, 25
      patients with PImax<70% of predicted were randomized to an 8-wk program of IMT
      (n=12) or placebo-IMT (n=13). PImax, inspiratory muscle endurance time, pulmonary
      function, peak oxygen uptake, and HR variability were evaluated before and after
      intervention. RESULTS: The prevalence of inspiratory muscle weakness was 29%. IMT
      significantly increased the PImax (118%) and the inspiratory muscle endurance
      time (495%), with no changes in pulmonary function, functional capacity, or
      autonomic modulation. There were no significant changes with placebo-IMT.
      CONCLUSIONS: Patients with type 2 diabetes may frequently present inspiratory
      muscle weakness. In these patients, IMT improves inspiratory muscle function with
      no consequences in functional capacity or autonomic modulation.

PMID- 21200343
TI  - Breath-hold diving: respiratory function on the longer term.
AB  - PURPOSE: Extensive breath-hold (BH) diving imposes high pulmonary stress by
      performing voluntary lung hyperinflation maneuvers (glossopharyngeal
      insufflation, GI), hyperinflating the lung up to 50% of total lung capacity.
      Breath-hold durations of up to 10 min without oxygen support may also presume
      cerebral alterations of respiratory drive. Little is known about the long-term
      effects of GI onto the pulmonary parenchyma and respiratory adaptation processes
      in this popular extreme sport. METHODS: Lung function assessments and subsequent
      measures of pulmonary static compliance were obtained for 5 min after GI in 12
      elite competitive breath-hold divers (BHD) with a mean apnea diving performance
      of 6.6 yr. Three-year follow-up measurements were performed in 4 BHD. Respiratory
      drive was assessed in steady-state measurements for 6% and 9% CO2 in ambient air.
      RESULTS: Short-term pulmonary stress effects for static compliance during GI
      (13.75 L.kPa) could be confirmed in these 12 divers without exhibiting permanent
      changes to the lungs' distensibility (7.41 L.kPa) or lung function parameters as
      confirmed by the follow-up measurements and for 4 BHD after 3 yr (P>0.05).
      Respiratory drive was significantly reduced in these BHD revealing a
      characteristic breathing pattern with a significant increase in VE and mouth
      occlusion pressure (P0.1) between free breathing and 6% CO2, as well as between
      6% CO2 and 9% CO2 (all P<0.001). CONCLUSION: BH diving with performance of GI
      does not permanently alter pulmonary distensibility or impair ventilatory flows
      and volumes. A blunted response to elevated CO2 concentrations could be
      demonstrated, which was supportive of the hypothesis that CO2 tolerance is a
      training effect due to BH diving rather than being an inherited phenomenon.

PMID- 21200344
TI  - Energetics and biomechanics of inclined treadmill walking in obese adults.
AB  - Brisk walking is a recommended form of exercise for obese individuals. However,
      lower-extremity joint loads and the associated risk of musculoskeletal injury or
      pathological disease increase with walking speed. Walking uphill at a slower
      speed is an alternative form of moderate intensity exercise that may reduce joint
      loading. PURPOSE: The purpose of this study was to quantify the energetics and
      biomechanics of level and uphill walking in obese adults. We hypothesized that
      compared to brisk level walking, walking slower up a moderate incline would
      reduce lower-extremity net muscle moments while providing appropriate
      cardiovascular stimulus. METHODS: Twelve obese adult volunteers, with mass of
      100.5+/-15.7 kg and body mass index of 33.4+/-2.6 kg.m (mean+/-SD), participated
      in this study. We measured oxygen consumption, ground reaction forces, and three
      dimensional lower-extremity kinematics while subjects walked on a dual-belt force
      measuring treadmill at several speed (0.50-1.75 m.s) and grade (0 degrees -9
      degrees ) combinations. We calculated metabolic rate, loading rates, and net
      muscle moments at the hip, knee, and ankle for each condition. RESULTS: Metabolic
      rates were similar across trials and were of moderate intensity (48.5%-59.8% of
      VO2max). Walking slower uphill significantly reduced loading rates and lower
      extremity net muscle moments compared with faster level walking. Peak knee
      extension and adduction moments were reduced by ~19% and 26%, respectively, when
      subjects walked up a 6 degrees  incline at 0.75 m.s versus level walking at 1.50
      m.s. CONCLUSIONS: These results suggest that walking at a relatively slow speed
      up a moderate incline is a potential exercise strategy that may reduce the risk
      of musculoskeletal injury/pathological disease while providing proper
      cardiovascular stimulus in obese adults.

PMID- 21200345
TI  - Carotid and peripheral atherosclerosis in male marathon runners.
AB  - PURPOSE: We measured extracoronary atherosclerotic plaque burden and its
      association with cardiovascular risk factors and with coronary atherosclerosis in
      male marathon runners. METHODS: We studied 100 male presumably healthy runners,
      aged 50-75 yr, who completed at least five marathons during the preceding 3 yr.
      Presence of plaque in the carotid, abdominal, and lower limb arteries was imaged
      using B-mode ultrasound. In all runners, traditional cardiovascular risk factors
      and the electron beam computed tomography-based coronary artery calcium (CAC)
      score were determined. RESULTS: Ten runners were free from any plaque in the
      carotid or peripheral arteries. Runners with plaque were older (58+/-6 vs 54+/-5
      yr, P=0.04), had a higher 10-yr Framingham risk score (7.2+/-3.8 vs 5.0+/-1.9,
      P=0.026), and tended to have a higher prevalence of CAC (76.7% vs 50.0%, P=0.07)
      compared with those without. Runners with CAC>=100 had larger peripheral artery
      diameters (aorta and iliac and common femoral arteries) but smaller lumen than
      runners with CAC<100, indicating atherosclerotic remodeling. A stepwise model
      selection process to predict CAC on the basis of age and peripheral
      atherosclerosis yielded a model as follows: log2(CAC+1)=0.181 age (yr)+0.435
      maximum carotid plaque thickness (mm)-6.487, with a coefficient of determination
      of 22.8%. However, positive and negative predictive values were too low to
      predict CAC>=100 with sufficient accuracy. CONCLUSIONS: The prevalence of carotid
      and peripheral atherosclerosis in marathon runners is high and is related to
      cardiovascular risk factors and the coronary atherosclerotic burden. Remodeling
      of peripheral arteries is greatest in runners with the most evidence of
      atherosclerosis. These data support an increased awareness of atherosclerosis
      prevalence and cardiovascular risk factors in marathon runners.

PMID- 21200346
TI  - Metabolic rate and accelerometer output during walking in people with Down
      syndrome.
AB  - People with Down syndrome (DS) have reduced gait stability and aerobic fitness
      that increase the metabolic rate during walking, potentially altering the
      relationship between metabolic rate and accelerometer output and lowering
      predictability of energy expenditure from accelerometry. PURPOSE: This study
      examined whether the relationship between metabolic rate and activity count rate
      differs between individuals with and without DS and whether predictability of
      metabolic rate is different between groups. METHODS: Metabolic rate was measured
      in METs with portable spirometry in 18 subjects with DS (24.7+/-6.7 yr; 10 women)
      and 18 subjects without DS (26.3+/-5.2 yr; 10 women) during five overground
      walking trials, each lasting 6 min, at 0.5, 0.75, 1.0, 1.25, and 1.5 m.s. A
      uniaxial accelerometer secured at the right side of the hip allowed for the
      determination of activity count rate. RESULTS: The relationship between METs and
      activity count rate in the two groups was analyzed with multilevel modeling with
      random intercepts and slopes, demonstrating a significant interaction between
      group and activity count rate (P<0.001). Separate models for each group showed
      that the activity count rate and its squared significantly predicted METs
      (P<=0.001). Actual and predicted METs did not differ in each group. Bland-Altman
      plots showed greater variability in the difference between actual and predicted
      METs for participants with DS. Mean absolute error of prediction was 19.92% and
      14.55% for participants with and without DS, respectively. CONCLUSIONS:
      Individuals with DS show altered METs to activity count rate relationship during
      overground walking and have lower predictability of metabolic rate from uniaxial
      accelerometer output than individuals without DS.

PMID- 21200347
TI  - Growth of left ventricular mass with military basic training in army recruits.
AB  - Exercise-induced left ventricular hypertrophy is well documented, but whether
      this occurs merely in line with concomitant increases in lean body mass is
      unclear. PURPOSE: Our aim was to model the extent of left ventricular hypertrophy
      associated with increased lean body mass attributable to an exercise training
      program. METHODS: Cardiac and whole-body magnetic resonance imaging was performed
      before and after a 10-wk intensive British Army basic training program in a
      sample of 116 healthy Caucasian males (aged 17-28 yr). The within-subjects
      repeated-measures allometric relationship between lean body mass and left
      ventricular mass was modeled to allow the proper normalization of changes in left
      ventricular mass for attendant changes in lean body mass. To linearize the
      general allometric model (Y=aXb), data were log-transformed before analysis; the
      resulting effects were therefore expressed as percent changes. We quantified the
      probability that the true population increase in normalized left ventricular mass
      was greater than a predefined minimum important difference of 0.2 SD, assigning a
      probabilistic descriptive anchor for magnitude-based inference. RESULTS: The
      absolute increase in left ventricular mass was 4.8% (90% confidence interval=3.5%
      6%), whereas lean body mass increased by 2.6% (2.1%-3.0%). The change in left
      ventricular mass adjusted for the change in lean body mass was 3.5% (1.9%-5.1%),
      equivalent to an increase of 0.25 SD (0.14-0.37). The probability that this
      effect size was greater than or equal to our predefined minimum important change
      of 0.2 SD was 0.78-likely to be important. CONCLUSIONS: After correction for
      allometric growth rates, left ventricular hypertrophy and lean body mass changes
      do not occur at the same magnitude in response to chronic exercise.

PMID- 21200348
TI  - Acceleration and force reveal different mechanisms of electromechanical delay.
AB  - INTRODUCTION: Electromechanical delay (EMD) represents a series of complex
      processes of converting an electrical stimulus to a mechanical response. To
      quantify the contribution of electrochemical and mechanical processes of EMD in
      the human biceps brachii muscle over a wide range of elbow joint angles, we
      determined the onset of muscle contraction and the beginning of force development
      by recording acceleration of skin surface over the muscle and elbow flexion
      force, respectively. METHODS: Ten healthy male volunteers underwent two
      experimental sessions, in which submaximal paired-pulse stimuli were applied
      percutaneously to the resting biceps brachii muscle at 10 different elbow joint
      angles from 40 degrees  to 130 degrees  (0 degrees  represents full extension).
      RESULTS: The electrical stimulation induced repeatable contractions, in which the
      test-retest reliability of time parameters was sufficiently high (intraclass
      correlation coefficient=0.84-0.88). The time for electrochemical process ranged
      between 3.1+/-0.8 and 3.6+/-0.9 ms and was independent of elbow joint angle
      (P=0.64). The time for mechanical process and the total duration of EMD, however,
      were significantly greater at elbow flexion positions than at 40 degrees , the
      most extended position in this study (P<0.05). Regression analysis revealed that
      at elbow flexion positions, the time for mechanical process increased
      significantly with decreasing the muscle-tendon length of the biceps brachii
      calculated from a musculoskeletal model (R=0.54, P<0.001). CONCLUSIONS: These
      results suggest that, in the human biceps brachii muscle, the prolongation of EMD
      at short muscle-tendon length is not attributed to the impairment of the
      electrochemical process of muscle contraction but to the increased slack within
      the muscle-tendon unit.

PMID- 21200349
TI  - Energy expenditure prediction using a miniaturized ear-worn sensor.
AB  - PURPOSE: This study aimed to predict human energy expenditure and activity type
      using a miniature lightweight ear-worn inertia sensor and a novel pattern
      recognition algorithm for activity detection. METHODS: This study used a protocol
      of 11 activities of daily living: lying down, standing, computer work, vacuuming,
      stairs, slow walking, brisk walking, slow running, fast running, cycling, and
      rowing. Subjects included 25 healthy randomized subjects (18 males and 7
      females). Each participant wore the ear sensor to record posture and linear
      acceleration, as well as the Cosmed K4b system for indirect calorimetry. The main
      outcome measure was the continuous energy expenditure per minute prediction for
      both task-known and task-blind estimation. RESULTS: The values for METs predicted
      using the proposed algorithm and the measured METs using the K4b showed good
      agreement with low values for the systematic bias (lying down=0.01, standing=
      0.02, computer work=-0.04, vacuuming=-0.17, stairs=-0.02, slow walking=0.01, fast
      walking=0.04, slow running=0.14, fast running=-0.35, cycling=0.32, and
      rowing=0.10). For task-blind prediction, the agreement between predicted and
      measured METs is also good with low values of the systematic bias (lying
      down=0.11, standing=0.14, computer work=-0.06, vacuuming=0.47, stairs=-0.47, slow
      walking=0.53, fast walking=-0.11, slow running=0.83, fast running=-1.18,
      cycling=0.31, and rowing=-0.67). Activity is also well predicted (for task-blind
      prediction) with an overall success rate of 88.99% and individual correct
      classification rates of lying down=89.62%, standing/computer work=99.10%,
      vacuuming=76.60%, stairs=89.13%, walking=85.11%, running=98.96%, and
      cycling=79.79%. CONCLUSIONS: The ear-worn sensor presented in this work is a
      novel lightweight device that can be used to predict energy expenditure for a
      range of activities without behavior interference or modification.

PMID- 21200350
TI  - Expression of alpha-gustducin in mammalian retinas.
AB  - alpha-Gustducin (Galpha-gust) is the alpha subunit of the heterotrimeric G
      protein complex specific for taste receptor cells of the tongue. However, it has
      been shown to be present in ectopic regions, such as airways and digestive tract.
      Recently, Galpha-gust was found within neurons in various regions of the mouse
      brain. In this study, we tested whether Galpha-gust is expressed in the mammalian
      retina. Galpha-gust was identified in mouse, rat, and rabbit retinas by western
      blot and immunohistochemistry analyses. Double-labeling experiments in the mouse
      retina clearly showed that Galpha-gust is exclusively expressed in the axon
      terminals of the rod bipolar cells. The evidence suggests that Galpha-gust may
      selectively participate in signal transduction in the axon terminals of rod
      bipolar cells in the mammalian retina.

PMID- 21200351
TI  - When leaf becomes neuter: event-related potential evidence for grammatical gender
      transfer in bilingualism.
AB  - This study addressed the question as to whether grammatical properties of a first
      language are transferred to a second language. Dutch-English bilinguals
      classified Dutch words in white print according to their grammatical gender and
      colored words (i.e. Dutch common and neuter words, and their English
      translations) according to their color. Both the classifications were made with
      the same hand (congruent trials) or different hands (incongruent trials).
      Performance was more erroneous and the error-elated negativity was enhanced on
      incongruent compared with congruent trials. This effect was independent of the
      language in which words were presented. These results provide evidence for the
      fact that bilinguals may transfer grammatical characteristics of their first
      language to a second language, even when such characteristics are absent in the
      grammar of the latter.

PMID- 21200352
TI  - Correlation of left ventricular count rate with patient weight in Tc-99m
      myocardial perfusion imaging.
AB  - OBJECTIVES: The aim of this retrospective investigation was to devise a protocol
      for obtaining consistent myocardial counts for patients attending myocardial
      perfusion imaging. METHODS: A total of 229 patients were included in the study
      sample. For each rest single-photon emission computed tomography data set, a
      three-dimensional ellipse was manually defined to isolate the left ventricle. The
      count rate per voxel was measured from a threshold region of interest covering
      the normally perfused myocardium (70-100% of maximum counts). Data were
      normalized for net administered activity and plotted against patient weight. The
      correlation between the variables was used to derive a protocol for adjusting
      injected activity or scan time to obtain consistent counts from patient to
      patient. RESULTS: There was a significant correlation between counts per second
      per voxel per MBq and patient weight. The best fit was achieved with an inverse
      model. A correlation equation was derived for patients weighing more than 60 kg
      (combined R=0.79): [CPS/voxel/MBq=(0.0163/weight(kg)]-3.68*10+A in which A, a sex
      dependent constant, was 0 for men and -2.920*10 for women. CONCLUSION: There was
      a significant inverse correlation between patient weight and CPS per voxel per
      MBq.

PMID- 21200354
TI  - What drives adaptive gait changes to acutely presented monocular blur?
AB  - PURPOSE: To determine whether gait alterations due to monocular spherical lens
      blur were a safety strategy or driven by lens magnification. METHODS: Adaptive
      gait and visual function were measured in 10 older adults (mean age, 74.9 +/- 4.8
      years) with the participants' optimal refractive correction and when monocularly
      blurred with +/-1.00 DS and +/-2.00 DS lens over the dominant eye. Adaptive gait
      measurements for the lead and trail foot included foot position before the raised
      surface, toe clearance of the raised surface edge, and foot position on the
      raised surface. Vision measurements included binocular visual acuity, contrast
      sensitivity, and stereoacuity. RESULTS: Equal levels of monocular positive and
      negative spherical lens blur led to very different stepping strategies when
      negotiating a raised surface. Positive blur lenses led to an increased vertical
      toe clearance and reduced distance of the lead foot position on the raised
      surface. Negative lenses led to the opposite of these changes. CONCLUSIONS:
      Findings suggest that step negotiation strategies were driven by the
      magnification effect provided by the spherical lenses. Steps appeared closer and
      larger with magnification from positive lenses and further away and smaller with
      minification from negative lenses and gait was adjusted accordingly. These
      results suggest that previously reported adaptive gait changes to monocular
      spherical lens blur were not safety strategies as previously suggested but driven
      by lens magnification. The significance of these findings in terms of prescribing
      large refractive changes in frail older patients is discussed.

PMID- 21200353
TI  - Influence of motion smear on visual acuity in simulated infantile nystagmus.
AB  - PURPOSE: In persons with infantile nystagmus (IN), visual acuity correlates with
      the duration of the foveation period of the nystagmus waveform, i.e., when the
      retinal image is on or near the fovea and moves with low velocity. In this study,
      we asked how acuity is affected by the non-foveating phases of the nystagmus
      waveform, when the velocity of retinal image motion is substantially higher.
      METHODS: Visual acuity was measured in three normal observers for high contrast,
      four-orientation single T-stimuli, presented during image motion that simulated
      either the whole jerk-IN waveform (whole-waveform) or only the foveation periods
      of the IN waveform (foveation-only). Simulated foveation durations ranged from 20
      to 120 ms. For both motion waveforms, we displayed the acuity target for
      different number of cycles to examine whether acuity benefits from multiple
      presentations of the stimulus. RESULTS: As expected, visual acuity improves with
      longer simulated foveation durations in both the whole-waveform and foveation
      only conditions. Acuity is consistently better (by ~0.1 logarithm of the minimum
      angle of resolution) in the foveation-only than the whole-waveform condition,
      indicating that the high-velocity image motion during the simulated IN waveform
      has a detrimental effect. This difference in acuity between the two waveform
      conditions increases with the number of cycles, apparently because summation
      occurs across cycles in the foveation-only condition but not in the whole
      waveform condition. CONCLUSIONS: In normal observers, visual acuity in the
      presence of a simulated nystagmus waveform is limited not only by the duration of
      the foveation periods, but also by the non-foveating phases of the waveform.
      However, because persons with IN report little or no motion smear in association
      with their nystagmus, it remains unclear whether the rapid retinal image motion
      during the non-foveating phases of the nystagmus waveform generates a similar
      degradation of visual acuity in IN.

PMID- 21200355
TI  - Whole-surface characterization of progressive addition lenses.
AB  - PURPOSE: To characterize and compare progressive addition lens (PAL) surfaces in
      terms of the Zernike polynomials. METHODS: We examine the spherocylindrical
      characteristics of PALs by performing a physical surface height measurement of
      three lenses. Surface shape is described as the sum of Zernike polynomials. These
      data were used to analyze and compare each surface, using the second derivatives
      of surface height. We compare PALs to each other and to a prototypical
      progressive surface, i.e., the Alvarez lens surface. RESULTS: The high order
      freeform surfaces of PALs produce a gradient of spherical power across the lens
      aperture and also a profile of astigmatic power with high order aberration. Each
      lens is similar to the Alvarez surface, but each has characteristics that
      differentiate it from the others. Each high order Zernike term contributes sphere
      and/or astigmatism, and aberration, to the surface. CONCLUSIONS: This approach to
      PAL analysis, in which the entire lens surface is defined and expressed as the
      sum of Zernike polynomial terms, is different from most previous approaches in
      which a lens is described as an array of subapertures. It is potentially an
      efficient and useful method for defining and designing PAL surfaces.

PMID- 21200356
TI  - Evaluation of single pixel step sizes in visual acuity assessment.
AB  - PURPOSE: Adaptive thresholding procedures (e.g., ZEST) benefit from testing near
      the current estimate of threshold. Therefore, small increments may improve
      precision of these techniques. We evaluated the validity of visual acuity
      assessment when letters are not constrained to a multiple of 5 pixels high.
      METHODS: Snellen letters were presented over a +/-5 pixel range spanning the
      final threshold estimate. Sizes that were a multiple of 5 pixels (e.g., 20 and
      25) were presented 160 times, and other sizes were presented 40 times. This
      resulted in 320 letter presentations at multiples of 5 and at non-multiples of 5.
      Post hoc ZEST procedures were used to compute acuity threshold estimates based on
      testing at those two sets of sizes. Two subjects participated: subject 1 for the
      right and left eyes and subject 2 in two sessions with binocular viewing.
      Psychometric functions were fit to the data and were used to model simulated
      observers. Simulations were run for each data set, and the number of
      presentations at each size matched the number presented to the subject. Ninety
      percent limits for proportion correct at each letter size were determined from
      the simulation data, and these limits were used as criteria for identifying
      outliers in the subject's data. RESULTS: No significant difference in acuity
      thresholds were found when letters were rendered in multiples of 5 pixel heights
      vs. letters without this constraint. Empirical data fell within the bounds
      defined by simulations, with no idiosyncratic results found for either set of
      letter sizes. CONCLUSIONS: Letter sizes that do not conform to a multiple of 5
      pixel letter height yield valid acuity scores. This facilitates adaptive
      psychometric procedures for acuity testing, such as ZEST and QUEST, in which
      letter sizes are selected to be as close to the current estimate of threshold
      size as possible.

PMID- 21200358
TI  - Mortality and morbidity among infants at high risk for severe respiratory
      syncytial virus infection receiving prophylaxis with palivizumab: a systematic
      literature review and meta-analysis.
AB  - OBJECTIVES: A systematic literature review and meta-analysis was performed to
      evaluate the impact of prophylaxis with palivizumab on mortality and morbidity
      associated with respiratory syncytial virus infection in infants at high risk (<=
      35 wks of gestational age, chronic lung disease, or congenital heart disease).
      DATA SOURCES: MEDLINE, EMBASE, and Current Contents were used. MEDLINE was
      searched from January 1, 1990 to May 16, 2007. The bibliographies of accepted
      studies and recent reviews and proceedings from the past 2 yrs were searched to
      identify additional relevant studies. STUDY SELECTION: Randomized controlled
      trials and prospective or retrospective cohort studies evaluating all-cause and
      respiratory syncytial virus-specific mortality, respiratory syncytial virus
      hospitalizations, and health care use in infants at high risk for respiratory
      syncytial virus infection receiving prophylaxis with palivizumab. DATA
      EXTRACTION: Data elements from each accepted study were extracted by one
      researcher and confirmed by a second researcher. Differences were resolved before
      data entry and analysis. DATA SYNTHESIS: A total of 2473 citations were screened
      and ten comparative studies of palivizumab prophylaxis evaluating >15,000 infants
      were included. Comparisons of mortality and hospitalization outcomes between
      infant groups using prophylaxis and not using prophylaxis were made using meta
      analyses. CONCLUSIONS: Prophylaxis and nonprophylaxis infant groups appeared to
      be comparable at baseline. All-cause mortality during the respiratory syncytial
      virus season was 12 of 6380 (0.19%) for infants with prophylaxis vs. 33 of 8182
      (0.53%) for infants without prophylaxis (Peto odds ratio, 0.30; 95% confidence
      interval, 0.17-0.55). Only five respiratory syncytial virus-specific deaths were
      reported, and the majority of the studies did not report respiratory syncytial
      virus-related deaths. The rate of respiratory syncytial virus hospitalization was
      significantly lower among preterm infants with prophylaxis compared with those
      without prophylaxis (4.1% vs. 10.4%; odds ratio, 0.35; 95% confidence interval,
      0.25-0.47). Prophylaxis with palivizumab was associated with a reduction in all
      cause mortality and respiratory syncytial virus hospitalization among preterm
      infants at high risk. Additional research on cause of death among infants at high
      risk is needed.

PMID- 21200359
TI  - 2009 Influenza A H1N1 infections: delays in starting treatment with oseltamivir
      were associated with a more severe disease.
AB  - Respiratory failure has been the main severe complication described in pediatric
      patients with influenza A H1N1 2009 (pandemic H1N1) infection. We describe the
      pandemic H1N1 2009 disease in children who required hospital admission and the
      patients' data associated with pediatric intensive care unit admission.
      Respiratory failure was the main complication. Extrapulmonary manifestations were
      also observed. Of the 127 patients, 24 required pediatric intensive care unit
      admission. Four patients died. Patients admitted with chronic conditions and
      those in whom oseltamivir was delayed more than 72 hours had a more severe
      disease.

PMID- 21200360
TI  - Immunogenicity and safety of an investigational quadrivalent meningococcal ACWY
      tetanus toxoid conjugate vaccine in healthy adolescents and young adults 10 to 25
      years of age.
AB  - BACKGROUND: An investigational quadrivalent Neisseria meningitidis serogroups A,
      C, W-135, and Y tetanus toxoid conjugate vaccine (MenACWY-TT) has been developed
      to expand available options for vaccination against invasive meningococcal
      disease. METHODS: A total of 784 healthy adolescents and young adults 11 to 25
      years of age were randomized (3:1) to receive a single dose of the MenACWY-TT
      vaccine or a licensed MenACWY diphtheria toxoid conjugate vaccine (MenACWY-DT).
      An additional nonrandomized group of 88 subjects 10 years of age received the
      MenACWY-TT vaccine only (MenACWY-TT/10). Immunogenicity was assessed 1 month
      postvaccination by human complement serum bactericidal assay (hSBA) for all
      serogroups. Solicited local and general symptoms were recorded for 8 days
      postvaccination and safety outcomes for 6 months. RESULTS: One month
      postvaccination, 81.9% to 96.1% of subjects had hSBA titers >= 1:8 in the MenACWY
      TT group compared with 70.7% to 98.8% in the MenACWY-DT group. Exploratory
      analyses showed the proportion of subjects with hSBA titers >= 1:4 and >= 1:8 to
      be higher in the MenACWY-TT group than in the MenACWY-DT group for serogroups A,
      W-135, and Y. GMTs adjusted for age strata and baseline titer 1 month
      postvaccination were higher in the MenACWY-TT group than in the MenACWY-DT group
      for all 4 serogroups. The percentage of subjects reporting solicited local and
      general symptoms of any or Grade 3 severity or serious adverse events was similar
      between the 2 groups. Immune response and reactogenicity in the MenACWY-TT/10
      group was similar to that in the MenACWY-TT group, except for higher hSBA-MenA
      GMTs in the MenACWY-TT/10 group. CONCLUSIONS: The investigational MenACWY-TT
      vaccine was immunogenic in adolescents and young adults, with an acceptable
      safety profile.

PMID- 21200361
TI  - Pneumococcal nasopharyngeal carriage among infants born to human immunodeficiency
      virus-infected mothers immunized with pneumococcal polysaccharide vaccine during
      gestation.
AB  - BACKGROUND: We have previously shown that 23-valent pneumococcal polysaccharide
      vaccine (PPV) is immunogenic in human immunodeficiency virus (HIV)-infected
      mothers and provides vaccine-induced antibodies to the infant. We compared the
      nasopharyngeal pneumococcal colonization (NPC) rates in <6-month-old infants born
      to HIV-infected mothers, according to immunization with PPV during pregnancy.
      METHODS: NPC was evaluated in 45 term infants born to vaccinated women (PPV+) and
      in 60 infants in a control group (PPV-), at 2 months (+/-30 days), 4 months (+/
      30 days), and 6 months (+/-30 days) of age. RESULTS: A total of 82 infants
      completed the study (at least 2 of 3 evaluations), 35 (77%) in the PPV+ and 47
      (78.3%) in the PPV- groups, respectively. Infant gender, HIV infection status,
      number of adults, children, and smokers in the household, day-care attendance,
      occurrence of respiratory signs, and cotrimoxazole use were similar in both
      groups. NPC rates increased equally with age in both groups (2 months = 26.7% vs.
      25.6%; 4 months = 34.5% vs. 38.6%; 6 months = 38.7% vs. 56.3%, in PPV+ and PPV-,
      respectively). After controlling for potential confounders, we found no
      association between maternal vaccination and infant pneumococcal carriage
      (adjusted odds ratio = 0.70; 95% confidence interval: 0.23, 2.21) CONCLUSIONS:
      Vaccination of HIV-infected mothers with PPV did not protect infants younger than
      6 months of age from nasopharyngeal pneumococcal carriage.

PMID- 21200362
TI  - Temporal association between rhinovirus circulation in the community and invasive
      pneumococcal disease in children.
AB  - BACKGROUND: Mucosal coinfections with respiratory viruses and Streptococcus
      pneumoniae are common, but the role of rhinovirus infections in the development
      of invasive pneumococcal disease (IPD) in children has not been studied. METHODS:
      During 1995 and 2007, we analyzed the association of IPD in children less than 5
      years of age with respiratory virus epidemics by combining data from the National
      Infectious Disease Register, 3 prospective epidemiologic studies, and the
      database of the Department of Virology, University of Turku, Finland. RESULTS:
      The mean IPD rate in children younger than 5 years of age in Finland was 2.9
      cases per week (95% confidence interval [CI], 2.5-3.3) during periods of high
      rhinovirus activity, and 1.4 (95% CI, 1.2-1.6) during periods of low rhinovirus
      activity (P < 0.001). The IPD rate correlated with the rhinovirus activity
      recorded at the Department of Virology (correlation coefficient, 0.23; P = 0.001)
      and in the epidemiologic studies (correlation coefficients, 0.28, 0.25, and
      0.31). The IPD rate was moderately increased during periods of high respiratory
      syncytial virus activity (mean, 2.1 cases per week; 95% CI, 1.8-2.3) compared
      with periods of low respiratory syncytial virus activity (mean, 1.7; 95% CI, 1.6
      1.9; P = 0.008). There were no differences in the IPD rate between the periods of
      high and low influenza activity. CONCLUSIONS: Rhinovirus circulation in the
      community had an association with IPD in children younger than 5 years of age.
      This study suggests that rhinovirus infection may be a contributor in the
      development of IPD in the population of young children.

PMID- 21200363
TI  - Perfusion storage reduces apoptosis in a porcine kidney model of donation after
      cardiac death.
AB  - BACKGROUND: Donation after cardiac death (DCD) kidneys suffer a high incidence of
      delayed graft function attributable to warm ischemia and cold ischemia (CI).
      Neither the mechanism of injury nor type of cell death has been described.
      Clinical studies suggest that perfusion storage (PS) of DCD kidneys may reduce
      injury although the mechanism of protection is unknown. In a porcine model of
      DCD, we hypothesized that DCD kidneys have increased caspase-1 due to warm
      ischemia (WI) and increased caspase-3 and apoptosis due to CI. METHODS: Male
      Yorkshire pigs subjected to cardiac death were perfused with cold University of
      Wisconsin solution. The perfused kidneys were removed and stored in cold
      University of Wisconsin solution for 24 hr. Kidney biopsies were obtained before
      cardiac death and at 0 and 24 hr of CI. RESULTS: There was an increase in caspase
      1 activity due to WI before cold preservation. CI was associated with a massive
      increase in apoptosis, caspase-3/7 activity, and caspase-3 protein expression.
      Next, we hypothesized that PS would protect against apoptosis. We compared DCD
      kidneys subjected to static versus PS for 24 hr. PS significantly reduced
      proximal tubular apoptosis and was associated with increased B-cell lymphoma
      extra large, and hypoxia-inducible transcription factor-1alpha. CONCLUSIONS:
      These findings suggest that in DCD kidneys, WI preferentially activates caspase
      1, whereas CI activates caspase-3 and causes apoptosis. PS may protect DCD
      kidneys through activation of antiapoptotic pathways involving B-cell lymphoma
      extra large and hypoxia-inducible transcription factor-1alpha.

PMID- 21200364
TI  - Unique cellular and mitochondrial defects mediate FK506-induced islet beta-cell
      dysfunction.
AB  - OBJECTIVE: To determine biological mechanisms involved in posttransplantation
      diabetes mellitus caused by the immunosuppressant tacrolimus (FK506). METHODS:
      INS-1 cells and isolated rat islets were incubated with vehicle or FK506 and
      harvested at 24-hr intervals. Cells were assessed for viability, apoptosis,
      proliferation, cell insulin secretion, and content. Gene expression studies by
      microarray analysis, quantitative polymerase chain reaction, and motifADE
      analysis of the microarray data identified potential FK506-mediated pathways and
      regulatory motifs. Mitochondrial functions, including cell respiration,
      mitochondrial content, and bioenergetics were assessed. RESULTS: Cell
      replication, viability, insulin secretion, oxygen consumption, and mitochondrial
      content were decreased (P<0.05) 1.2-, 1.27-, 1.77-, 1.32-, and 1.43-fold,
      respectively, after 48-hr FK506 treatment. Differences increased with time. FK506
      (50 ng/mL) and cyclosporine A (800 ng/mL) had comparable effects. FK506
      significantly decreased mitochondrial content and mitochondrial bioenergetics and
      showed a trend toward decreased oxygen consumption in isolated islets. Cell
      apoptosis and proliferation, mitochondrial DNA copy number, and ATP:ADP ratios
      were not significantly affected. Pathway analysis of microarray data showed FK506
      modification of pathways involving ATP metabolism, membrane trafficking, and
      cytoskeleton remodeling. PGC1-alpha mRNA was down-regulated by FK506. MotifADE
      identified nuclear factor of activated T-cells, an important mediator of beta
      cell survival and function, as a potential factor mediating both up- and down
      regulation of gene expression. CONCLUSIONS: At pharmacologically relevant
      concentrations, FK506 decreases insulin secretion and reduces mitochondrial
      density and function without changing apoptosis rates, suggesting that
      posttransplantation diabetes induced by FK506 may be mediated by its effects on
      mitochondrial function.

PMID- 21200365
TI  - Liver transplantation for hepatic metastases of neuroendocrine pancreatic tumors:
      a survival-based analysis.
AB  - BACKGROUND: Liver transplantation (LT) has been accepted as a treatment in
      selected cases of neuroendocrine tumors (NETs) with hepatic metastases. PATIENTS
      AND METHODS: A systematic review of the literature was conducted to evaluate long
      term patient survival in the instances of LT for pancreatic NET. Univariate and
      multivariate regression analyses and survival analysis were performed. RESULTS:
      Fifty-three clinical studies were screened. Data from 20 studies encompassing 89
      transplanted patients were included in the study. Most primary tumors were
      endocrine pancreatic tumors (n=69), with gastrinomas representing the most
      frequent diagnosis (n=21). There were 61 functioning pancreatic NET. Simultaneous
      LT and pancreatic NET resections were performed in 45 instances. Cumulative 1-, 3
      , and 5-year survival was 71%, 55%, and 44%, respectively, with a calculated mean
      survival of 54.45+/-6.31 months. Vasoactive intestinal peptide (VIPomas) had the
      best overall survival. Recurrence-free survival at 1, 3, and 5 years was 84%,
      47%, and 47%, respectively. Recipient age more than or equal to 55 years
      (P=0.0242) and simultaneous LT-pancreatic resection (P=0.0132) were found to be
      significant predictors of worse survival by both univariate and multivariate Cox
      proportional hazard analyses. A scoring system was developed, with prognostic
      points assigned as follows: age more than or equal to 55 years:age less than 55
      years=1:0 points and simultaneous LT-pancreatic resection:LT alone=1:0 points.
      This stratification delineated three separate population samples corresponding to
      patients with scores of 0, 1, and 2, respectively. The calculated 5-year survival
      for scores 0, 1, and 2 was 61%, 40%, and 0%, respectively (P=0.0023).
      CONCLUSIONS: Despite the limitations of this retrospective analysis, good results
      can be achieved even for pancreatic NET primaries if the above-proposed scoring
      system is applied.

PMID- 21200366
TI  - Geographic inequity in access to livers for transplantation.
AB  - BACKGROUND: Liver transplantation offers life-saving therapy for patients with
      decompensated liver disease or T2 hepatocellular carcinomas. In the United
      States, deceased donor livers are primarily allocated by Model for End-Stage
      Liver Disease (MELD) score within each of the country's more than 50 donation
      service areas (DSAs). Variation in DSA size, population, and organ availability
      have engendered concern that unequal access to deceased donor livers across DSAs
      contributes to geographic variability in outcome. METHODS: To determine the
      extent to which DSA variability in organ availability correlated with combined
      waitlist and posttransplant mortality, we analyzed retrospectively national
      waitlist and posttransplant data for a 7-year period after implementation of the
      current MELD-based allocation system. RESULTS: Marked variation among DSAs was
      evident in death rate (3.3-fold), transplant rate (20-fold), and mean transplant
      MELD (>10 points). Death rate correlated with organ availability was assessed by
      transplant rate and transplant MELD. DSAs with low organ availability included
      the country's largest cities, had more new listings per capita, larger waitlists,
      more transplant centers per DSA, and a higher proportion of black and Asian
      patients. DSAs of organ shortage were also characterized by more frequent dual
      listing at another transplant center, more living donor liver transplants, and
      increased average length of the transplant admission. CONCLUSIONS: Geographic
      differences in deceased donor organ availability contribute to variation in
      overall death rate of liver transplant patients, shape the clinical practice of
      transplant, and influence the resources consumed per transplant. Geographic
      variation in organ access results primarily from rates of listing rather than
      donation. Our findings highlight the need to restructure organ distribution areas
      to achieve equal access to deceased donor livers for transplantation in the
      United States.

PMID- 21200368
TI  - Graves' disease. When thyroid hormones run wild.

PMID- 21200367
TI  - Allogenic skeletal myoblast transplantation in acute myocardial infarction model
      rats.
AB  - BACKGROUND: The limitations of syngenic cell therapy include patient safety and
      quality control of the source cells. Therefore, it is important to develop and
      assess procedures using allogenic cells. We investigated the impact of allogenic
      skeletal myoblast (SMB) transplantation on acute myocardial infarction with
      respect to immune response, donor cell survival, and therapeutic efficacy.
      METHODS: Female Lewis rats underwent proximal left anterior descending coronary
      artery ligation. Fifteen minutes later, they underwent major histocompatibility
      (MHC)-matched Lewis SMB transplantation (group S) and MHC-mismatched ACI SMB
      transplantation (group A), or treated with buffer injection as a control (group
      C). RESULTS: Flow cytometry showed that the SMBs expressed MHC antigens and B7
      signal molecules in vitro. In group A, transcription levels of interleukin-2
      receptor and interferon-gamma were significantly increased 7 days after
      transplantation, and the area surrounding the donor SMBs was intensely
      infiltrated with CD4- and CD8-positive cells. Estimation of the number of donor
      cells in the recipient left ventricular chamber revealed that except for day 0,
      group A had fewer donor SMBs, which disappeared faster, compared with group S.
      Echocardiography demonstrated that the ejection fraction (EF) of group A was
      lower than that of group S. CONCLUSION: MHC-mismatched allogenic SMB
      transplantation in infarcted myocardium induces the immune response and
      acceleration of donor cell clearance, decreasing the therapeutic effect. Donor
      cell survival and inflammation may play important roles in the therapeutic
      mechanism of SMB transplantation therapy for acute myocardial infarction.

PMID- 21200369
TI  - Government website offers data on health insurance options, health care law.

PMID- 21200370
TI  - Medicare provides more coverage for smoking cessation.

PMID- 21200371
TI  - FDA puts restrictions on use of controversial diabetes drug.

PMID- 21200372
TI  - Pacemakers and other heart devices. Help for a heartbeat.

PMID- 21200373
TI  - Mayo Clinic office visit. Genetic counseling. An interview with Carrie Zabel,
      M.S., C.G.C.

PMID- 21200374
TI  - The skinny on salad. Limit calories without sacrificing flavor.

PMID- 21200375
TI  - How can I get rid of calluses on my feet?

PMID- 21200376
TI  - Are cochlear implants an option for treating age-related hearing loss?

PMID- 21200377
TI  - Inhibition of monoamine oxidase activity by antidepressants and mood stabilizers.
AB  - OBJECTIVE: Monoamine oxidase (MAO), the enzyme responsible for metabolism of
      monoamine neurotransmitters, has an important role in the brain development and
      function, and MAO inhibitors have a range of potential therapeutic uses. We
      investigated systematically in vitro effects of pharmacologically different
      antidepressants and mood stabilizers on MAO activity. METHODS: Effects of drugs
      on the activity of MAO were measured in crude mitochondrial fraction isolated
      from cortex of pig brain, when radiolabeled serotonin (for MAO-A) or
      phenylethylamine (for MAO-B) was used as substrate. The several antidepressants
      and mood stabilizers were compared with effects of well known MAO inhibitors such
      as moclobemide, iproniazid, pargyline, and clorgyline. RESULTS: In general, the
      effect of tested drugs was found to be inhibitory. The half maximal inhibitory
      concentration, parameters of enzyme kinetic, and mechanism of inhibition were
      determined. MAO-A was inhibited by the following drugs: pargyline > clorgyline >
      iproniazid > fluoxetine > desipramine > amitriptyline > imipramine > citalopram >
      venlafaxine > reboxetine > olanzapine > mirtazapine > tianeptine > moclobemide,
      cocaine >> lithium, valproate. MAO-B was inhibited by the following drugs:
      pargyline > clorgyline > iproniazid > fluoxetine > venlafaxine > amitriptyline >
      olanzapine > citalopram > desipramine > reboxetine > imipramine > tianeptine >
      mirtazapine, cocaine >> moclobemide, lithium, valproate. The mechanism of
      inhibition of MAOs by several antidepressants was found various. CONCLUSIONS: It
      was concluded that MAO activity is acutely affected by pharmacologically
      different antidepressants at relatively high drug concentrations; this effect is
      inhibitory. There are differences both in inhibitory potency and in mechanism of
      inhibition between both several drugs and the two MAO isoforms. While MAO
      inhibition is not primary biochemical effect related to their therapeutic action,
      it can be supposed that decrease of MAO activity may be concerned in some effects
      of these drugs on serotonergic, noradrenergic, and dopaminergic
      neurotransmission.

PMID- 21200378
TI  - Role and regulation of EGFR in actin remodeling in sperm capacitation and the
      acrosome reaction.
AB  - To bind and fertilize the egg, the spermatozoon should undergo few biochemical
      and motility changes in the female reproductive tract collectively called
      capacitation. The capacitated spermatozoon binds to the egg zona pellucida, and
      then undergoes the acrosome reaction (AR), which allows its penetration into the
      egg. The mechanisms regulating sperm capacitation and the AR are not completely
      understood. In the present review, we summarize some data regarding the role and
      regulation of the epidermal growth factor receptor (EGFR) in these processes. In
      the capacitation process, the EGFR is partially activated by protein kinase A
      (PKA), resulting in phospholipase D (PLD) activation and actin polymerization.
      Protein kinase C alpha (PKCalpha), which is already activated at the beginning of
      the capacitation, also participates in PLD activation. Further activation of the
      EGFR at the end of the capacitation enhances intracellular Ca(2+) concentration
      leading to F-actin breakdown and allows the AR to take place. Under in vivo
      conditions, the EGFR can be directly activated by its known ligand epidermal
      growth factor (EGF), and indirectly by activating PKA or by transactivation
      mediated by G protein-coupled receptors (GPCRs) activation or by ouabain. Under
      physiological conditions, sperm PKA is activated mainly by bicarbonate, which
      activates the soluble adenylyl cyclase to produce cyclic adenosine monophosphate
      (cAMP), the activator of PKA. The GPCR activators angiotensin II or
      lysophosphatidic acid, as well as ouabain and EGF are physiological components
      present in the female reproductive tract.

PMID- 21200380
TI  - Implications of the immunoregulatory functions of mesenchymal stem cells in the
      treatment of human liver diseases.
AB  - Transplantation of mesenchymal stem cells (MSCs) has been recently studied in
      animal models, and in clinical trials of patients with fulminant hepatic failure,
      end-stage liver diseases and inherited metabolic disorders. Modulatory cytokines
      produced by MSCs can inhibit immunocyte proliferation and migration to the liver,
      thereby attenuating inflammatory injury and reducing hepatocyte apoptosis. In
      addition, MSCs play an important role in regressing liver fibrosis and in
      supporting the function, proliferation and differentiation of endogenous
      hepatocytes under appropriate conditions. Although remarkable progress has been
      achieved in basic and clinical MSC studies, optimal therapeutic regimens for the
      clinical application of MSCs, such as optimal doses, transplantation routine and
      interval period for transplantation, need to be elucidated in detail.
      Furthermore, the long-term safety and therapeutic efficacy of MSC transplantation
      should be evaluated in future clinical trials. This review summarizes our current
      understanding of the immunomodulatory effects of MSC therapies on human liver
      diseases.

PMID- 21200379
TI  - Role of dendritic cells: a step forward for the hygiene hypothesis.
AB  - The hygiene hypothesis was proposed more than two decades ago, but its mechanism
      remains unclear. This review focuses on recent advances in the field, especially
      on the role played by dendritic cells (DCs) and their modulating effects on
      various infections and allergic diseases, including allergic asthma. DCs isolated
      from mice long after the resolution of an infection were reported to have a
      significant modulating effect on allergen-specific Th2 responses in both in vitro
      and in vivo systems. These DCs showed DC1-like and/or tolerogenic DC capacity,
      which allowed for the inhibition of allergic responses by immune deviation
      (enhancing Th1 response) and immune regulation (through regulatory T-cell and Th2
      hyporesponsiveness) mechanisms. These findings represented a significant advance
      in the elucidation of the mechanisms underlying the hygiene hypothesis. Further
      investigation on the mechanisms by which DCs are 'educated' by infectious agents
      and the influence of the type, time, and extent of infections on this 'education'
      process will help us understand immune regulation in disease settings and in the
      rational design of preventive/therapeutic approaches to allergy/asthma and
      infections.

PMID- 21200381
TI  - CD4(+) T cell-released exosomes inhibit CD8(+) cytotoxic T-lymphocyte responses
      and antitumor immunity.
AB  - T cells secrete bioactive exosomes (EXO), but the potential immunoregulatory
      effect of T-cell EXO is largely unknown. In this study, we generated activated
      ovalbumin (OVA)-specific CD4(+) T cells in vitro via coculture of OVA-pulsed
      dendritic cells (DC(OVA)) with naive CD4(+) T cells derived from OVA-specific T
      cell receptor (TCR) transgenic OTII mice. CD4(+) T-cell EXO were then purified
      from the CD4(+) T-cell culture supernatants by differential ultracentrifugation.
      CD4(+) T-cell EXO exhibited the 'saucer' shape that is characteristic of EXO with
      a diameter between 50 and 100 nm, as assessed by electron microscopy, and
      contained the EXO-associated proteins LAMP-1, TCR and lymphocyte function
      associated antigen-1 (LFA-1), as determined by western blot. Flow cytometric
      analysis showed that CD4(+) T-cell EXO expressed CD4(+) T-cell markers (CD4, TCR,
      LFA-1, CD25 and Fas ligand), but to a lesser extent than CD4(+) T cells. We
      demonstrated that DC(OVA) took up CD4(+) T-cell EXO via peptide/major
      histocompatibility complex (pMHC) II/TCR and CD54/LFA-1 interactions. OVA
      specific CD4(+) T-cell EXO from OTII mice, but not ConA-stimulated polyclonal
      CD4(+) T-cell EXO from wild-type C57BL/6 mice inhibited DC(OVA)-stimulated in
      vitro CD4(+) T-cell proliferation and in vivo CD8(+) cytotoxic T lymphocyte (CTL)
      responses and antitumor immunity against OVA-expressing B16 melanoma BL6-10(OVA)
      cells. In addition, EXO derived from a T-cell hybridoma cell line, MF72.2D9,
      expressing an OVA-specific CD4(+) TCR, had a similar inhibitory effect as OTII
      CD4(+) T-cell EXO on CTL-mediated antitumor immunity. Taken together, our data
      indicate that antigen-specific T-cell EXO may serve as a new type of
      immunosuppressive reagent for use in transplant rejection and treatment of
      autoimmune diseases.

PMID- 21200382
TI  - Indoleamine 2,3-dioxygenase and regulatory dendritic cells contribute to the
      allograft protection induced by infusion of donor-specific splenic stromal cells.
AB  - It has been reported that splenic stromal cells (SSCs) are capable of directly
      supporting the development of CD11c(lo)CD45RB(+ )IL-10-producing dendritic cells
      (DCs) from lineage-negative c-kit(+) progenitor cells in the absence of exogenous
      cytokines. In vitro, DCs that differentiate on stromal cells suppress mixed
      leukocyte reaction responses and induce primary alloreactive CD4(+) T cells to
      differentiate into IL-10-producing Tr1 cells. However, the precise mechanisms by
      which these SSCs exert their regulatory functions in vivo remain undefined.
      Furthermore, their possible contribution to the development of allograft
      transplantation tolerance has yet to be examined. Here, we have used both murine
      skin and cardiac allograft transplantation models to explore whether in vivo
      alloresponses can be regulated by infusion with donor-derived SSCs and to
      investigate the possible mechanisms by which SSCs exert regulatory effects to
      prevent allograft rejection. We show that intravenous SSC infusion prolonged
      murine skin allograft survival. The prolonged graft survival is associated with
      augmentation of the generation of regulatory DC subsets and CD4(+)CD25(+)Foxp3(+)
      regulatory T cells (Tregs), as well as upregulation of the production of
      suppressive cytokines IL-10 and transforming growth factor (TGF)-beta. Moreover,
      we found that indoleamine 2,3-dioxygenase and SSC-derived regulatory DCs
      contribute to allograft protection by infusion of donor-specific SSCs. Our data
      suggest that donor-derived SSCs could be used as a therapeutic target to promote
      transplantation tolerance.

PMID- 21200383
TI  - Id1 has a physiological role in regulating early B lymphopoiesis.
AB  - Basic helix-loop-helix E proteins play critical roles in B-cell development by
      stimulating B cell-specific gene expression and immunoglobulin gene
      rearrangement. The function of E proteins can be effectively suppressed by their
      naturally occurring inhibitors, Id1 to 4. Ectopic expression of Id1 has been
      shown to block B-cell development at the early pro-B cell stage. However, whether
      Id1 plays a physiological role in controlling B lymphopoiesis was not known.
      Although Id1-deficient mice do not exhibit significant abnormalities in steady
      state B lymphopoiesis, we detected more robust B-cell engraftment in transplant
      recipients of Id1-deficient bone marrow compared to those of wild-type donor
      cells. In culture, Id1 ablation dramatically enhances B-lineage cell production
      without any marked effects on myeloid differentiation. Consistently, Id1
      expression was found in pro-B but not pre-B cells as measured by enhanced green
      fluorescent protein (EGFP) fluorescence and by quantitative reverse transcription
      PCR. Although loss of Id1 did not alter the number of B-cell colonies generated
      from whole bone marrow or the proliferation rate of developing B cells, B-cell
      colonies were detectable at a much earlier time point and the size of the
      colonies were larger. Therefore, we infer that Id1-deficient progenitors possess
      higher potential to differentiate to the pre-B cell stage when a proliferative
      burst occurs. Taken together, we present evidence to suggest that Id1 plays a
      physiological role in restraining the developmental progression, which may be
      important for proper B-cell differentiation in the bone marrow.

PMID- 21200384
TI  - Estrogen enhances the functions of CD4(+)CD25(+)Foxp3(+) regulatory T cells that
      suppress osteoclast differentiation and bone resorption in vitro.
AB  - Cross-talk has been shown to occur between the immune system and bone metabolism
      pathways. In the present study, we investigated the impact of
      CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells on osteoclastogenesis and bone
      resorption. Treg cells that were isolated and purified from peripheral blood
      mononuclear cells (PBMCs) of healthy adults inhibited both the differentiation of
      osteoclasts (OCs) from human embryo bone marrow cells (BMCs) and the pit
      formation in a dose-dependent manner. In cell cocultures, the production levels
      of both interleukin-10 (IL-10) and transforming growth factor-beta 1 (TGF-beta1)
      were proportionally upregulated as the ratio of Treg cells to BMCs was increased,
      and the inhibition of OC differentiation and bone resorption by Treg cells was
      completely reversed by anti-IL-10 and anti-TGF-beta1 antibodies. Treatment of BMC
      and Treg cell cocultures with 17beta-estradiol (E2) at concentrations between 10
      7 and 10-9 mol/l suppressed OC differentiation and bone resorption more
      efficiently than it did in cultures of BMCs alone; this enhanced suppression
      occurred via the stimulation of Treg cell IL-10 and TGF-beta1 expression. These
      data suggest that Treg cells suppress OC differentiation and bone resorption by
      secreting IL-10 and TGF-beta1. E2 enhances the suppressive effects of Treg cells
      on OC differentiation and bone resorption by stimulating IL-10 and TGF-beta1
      secretion from these cells. Therefore, Treg cell-derived IL-10 and TGF-beta1 are
      likely involved in the regulation of E2 on bone metabolism and represent
      potential therapeutic targets for the treatment of postmenopausal osteoporosis
      (PMO).

PMID- 21200385
TI  - A reversed CD4/CD8 ratio of tumor-infiltrating lymphocytes and a high percentage
      of CD4(+)FOXP3(+) regulatory T cells are significantly associated with clinical
      outcome in squamous cell carcinoma of the cervix.
AB  - In this study, 40 biopsy samples collected from cervical cancer patients at the
      First Affiliated Hospital of Xi'an Jiaotong University, China, were
      retrospectively assessed using immunohistochemistry for CD4(+) and CD8(+) tumor
      infiltrating lymphocytes (TILs) and were analyzed for the expression of FOXP3,
      OX40, granzyme B (GrB) and perforin (Prf). The proliferating index of the TILs
      was determined by assessing Ki67 expression. We determined the prognostic value
      of low and high numbers of TILs on survival by performing Kaplan-Meier analysis
      using median values as the cut-off points. Except for the number of
      CD4(+)FOXP3(+) regulatory T cells (Tregs) and the CD4/CD8 ratio, none of the
      CD4(+), CD8(+), OX40(+), GrB(+) or Prf(+) TILs were associated with the overall 5
      year survival rate. The 5-year survival rate was significantly lower in patients
      who had a high percentage of Tregs as compared with the those who had a lower
      percentage (35.3% versus 88.9%, P=0.001), while the 5-year survival rate was
      significantly higher in patients with a high CD4/CD8 ratio as compared with
      patients who had a low CD4/CD8 ratio (82.4% versus 44.4%, P=0.029). When we
      considered the deaths and surviving cases as separate groups, we found that both
      the number of CD4(+) T cells and the CD4/CD8 ratio were significantly lower in
      patients who died as compared with those who survived (26.33+/-11.80 versus
      47.79+/-38.18, P=0.023 and 0.60+/-0.25 versus 1.17+/-1.02, P=0.019,
      respectively). In conclusion, decreased proportions of tumor-infiltrating CD4(+)
      T cells with high percentages of Tregs and reversed CD4/CD8 ratios were
      significantly associated with the clinical outcome of patients with cervical
      carcinoma.

PMID- 21200386
TI  - Interferon regulatory factor 3-CL, an isoform of IRF3, antagonizes activity of
      IRF3.
AB  - Interferon regulatory factor 3 (IRF3), one member of the IRF family, plays a
      central role in induction of type I interferon (IFN) and regulation of apoptosis.
      Controlled activity of IRF3 is essential for its functions. During reverse
      transcription (RT)-PCR to clone the full-length open reading frame (ORF) of IRF3,
      we cloned a full-length ORF encoding an isoform of IRF3, termed as IRF3-CL, and
      has a unique carboxyl-terminus of 125 amino acids. IRF3-CL is ubiquitously
      expressed in distinct cell lines. Overexpression of IRF3-CL inhibits Sendai virus
      (SeV)-triggered induction of IFN-beta and SeV-induced and inhibitor of NF-kappaB
      kinase-epsilon (IKKepsilon)-mediated nuclear translocation of IRF3. When
      IKKepsilon is overexpressed, IRF3-CL is associated with IRF3. These results
      suggest that IRF3-CL, the alternative splicing isoform of IRF-3, may function as
      a negative regulator of IRF3.

PMID- 21200389
TI  - Identification and functional characterization of three novel alleles for the
      serotonin transporter-linked polymorphic region.
AB  - A promoter polymorphism in the serotonin transporter gene (5-HTTLPR) has been
      reported to confer relative risk for phenotypes (depression/anxiety) and
      endophenotypes (amygdala reactivity). In this report, we identify and
      characterize three rare 5-HTTLPR alleles not previously described in the human
      literature. The three novel alleles were identified while genotyping 5-HTTLPR in
      a family-based attention deficit hyperactivity disorder clinical population. Two
      of the novel alleles are longer than the common 16-repeat long (L) allele (17 and
      18 repeats) and the third is significantly smaller than the 14-repeat short (S)
      allele (11 repeats). The sequence and genetic architecture of each novel allele
      is described in detail. We report a significant decrease in the expression
      between the XL17 (17r) allele and the L(A) (16r) allele. The XS11 (11r) allele
      showed similar expression with the S (14r) allele. A 1.8-fold increase in
      expression was observed with the L(A)(16r) allele compared with the L(G) (16r)
      allele, which replicates results from earlier 5-HTTLPR expression experiments. In
      addition, transcription factor binding site (TFBS) analysis was performed using
      MatInspector (Genomatix) that showed the presence or absence of different
      putative TFBSs between the novel alleles and the common L (16r) and S (14r)
      alleles. The identification of rare variants and elucidation of their functional
      impact could potentially lead to understanding the contribution that the rare
      variant may have on the inheritance/susceptibility of multifactorial common
      diseases.

PMID- 21200387
TI  - Humanized mice are susceptible to Salmonella typhi infection.
AB  - Salmonella enterica serovar Typhi is a pathogen that only infects humans.
      Currently, there is no animal model for studying this pathogen. Recently,
      alymphoid RAG-2(-/-)/gamma(c)(-/-) mice engrafted with human leukocytes, known as
      humanized mice, have been successfully utilized to develop experimental models
      for several human-specific viral infections, including HIV, human-like dengue
      fever and hepatitis C virus. Little is known about the usefulness and feasibility
      of the humanized mouse model for the study of human-specific bacterial pathogens,
      such as S. typhi. The aim of this study was to determine if Salmonella enterica
      serovar Typhi could establish productive infection in humanized mice. Here we
      report that intravenous inoculation of S. typhi into humanized mice, but not
      controls, established S. typhi infections. High bacterial loads were found in the
      liver, spleen, blood and bone marrow of mice reconstituted with human leukocytes,
      but not in the unreconstituted control mice. Importantly, S. typhi-infected
      humanized mice lost significant body weight, and some of the infected mice
      displayed neurological symptoms. Our data suggest, for the first time, that
      humanized mice are susceptible to S. typhi challenge and that this model can be
      utilized to study the pathogenesis of S. typhi to develop novel therapeutic
      strategies.

PMID- 21200390
TI  - OTS highlights advance in basic and translational aspects of oligonucleotide
      research.

PMID- 21200393
TI  - Not an inside job: how can transplantation of relatively few exogenous satellite
      cells do what thousands of endogenous cells cannot?

PMID- 21200394
TI  - Bone metastasis: mechanisms and therapeutic opportunities.
AB  - The skeleton is one of the most common sites for metastatic cancer, and tumors
      arising from the breast or prostate possess an increased propensity to spread to
      this site. The growth of disseminated tumor cells in the skeleton requires tumor
      cells to inhabit the bone marrow, from which they stimulate local bone cell
      activity. Crosstalk between tumor cells and resident bone and bone marrow cells
      disrupts normal bone homeostasis, which leads to tumor growth in bone. The
      metastatic tumor cells have the ability to elicit responses that stimulate bone
      resorption, bone formation or both. The net result of these activities is
      profound skeletal destruction that can have dire consequences for patients. The
      molecular mechanisms that underlie these painful and often incurable consequences
      of tumor metastasis to bone are beginning to be recognized, and they represent
      promising new molecular targets for therapy.

PMID- 21200395
TI  - The role of mitochondria in osteoarthritis.
AB  - Mitochondria are important regulators of cellular function and survival that may
      have a key role in aging-related diseases. Mitochondrial DNA (mtDNA) mutations
      and oxidative stresses are known to contribute to aging-related changes.
      Osteoarthritis (OA) is an aging-associated rheumatic disease characterized by
      articular cartilage degradation and elevated chondrocyte mortality. Articular
      cartilage chondrocytes survive and maintain tissue integrity in an avascular, low
      oxygen environment. Recent ex vivo studies have reported mitochondrial
      dysfunction in human OA chondrocytes, and analyses of mitochondrial electron
      transport chain activity in these cells show decreased activity of Complexes I,
      II and III compared to normal chondrocytes. This mitochondrial dysfunction may
      affect several pathways that have been implicated in cartilage degradation,
      including oxidative stress, defective chondrocyte biosynthesis and growth
      responses, increased cytokine-induced chondrocyte inflammation and matrix
      catabolism, cartilage matrix calcification, and increased chondrocyte apoptosis.
      Mitochondrial dysfunction in OA chondrocytes may derive from somatic mutations in
      the mtDNA or from the direct effects of proinflammatory mediators such as
      cytokines, prostaglandins, reactive oxygen species and nitric oxide.
      Polymorphisms in mtDNA may become useful as biomarkers for the diagnosis and
      prognosis of OA, and modulation of serum biomarkers by mtDNA haplogroups supports
      the concept that mtDNA haplogroups may define specific OA phenotypes in the
      complex OA process.

PMID- 21200396
TI  - Prevention: will an aspirin a day keep the colorectal cancer away?

PMID- 21200398
TI  - Top doc.

PMID- 21200399
TI  - Water.

PMID- 21200400
TI  - Natural healing. How does Nature repair itself after an oil spill?

PMID- 21200397
TI  - The good viruses: viral mutualistic symbioses.
AB  - Although viruses are most often studied as pathogens, many are beneficial to
      their hosts, providing essential functions in some cases and conditionally
      beneficial functions in others. Beneficial viruses have been discovered in many
      different hosts, including bacteria, insects, plants, fungi and animals. How
      these beneficial interactions evolve is still a mystery in many cases but, as
      discussed in this Review, the mechanisms of these interactions are beginning to
      be understood in more detail.

PMID- 21200401
TI  - In the womb's shadow. The theory of prenatal programming as the fetal origin of
      various adult diseases is increasingly supported by a wealth of evidence.

PMID- 21200403
TI  - Multiple death pathways in TNF-treated fibroblasts: RIP3- and RIP1-dependent and
      independent routes.

PMID- 21200405
TI  - Method of obtaining wavefront slope data from through-focus point spread function
      measurements.
AB  - A method is described for analyzing point source imagery collected with various
      amounts of defocus to obtain wavefront slope data at the exit pupil of an imaging
      system. Integration of this slope data yields the system wavefront aberration
      function. The method is based on a geometric optics interpretation of intensity
      point spread function measurements in the caustic region near focus. Algorithm
      performance is examined through Monte Carlo simulations. Application of the
      method to segmented-aperture systems is also explored. The proposed method is
      used to generate initial wavefront estimates for an iterative phase retrieval
      algorithm, significantly improving the capture range over a blind phase retrieval
      approach when segment tilt errors are large.

PMID- 21200406
TI  - Directional statistics-based reflectance model for isotropic bidirectional
      reflectance distribution functions.
AB  - We introduce a novel parametric bidirectional reflectance distribution function
      (BRDF) model that can accurately encode a wide variety of real-world isotropic
      BRDFs with a small number of parameters. The key observation we make is that a
      BRDF may be viewed as a statistical distribution on a unit hemisphere. We derive
      a novel directional statistics distribution, which we refer to as the
      hemispherical exponential power distribution, and model real-world isotropic
      BRDFs as mixtures of it. We derive a canonical probabilistic method for
      estimating the parameters, including the number of components, of this novel
      directional statistics BRDF model. We show that the model captures the full
      spectrum of real-world isotropic BRDFs with high accuracy, but a small footprint.
      We also demonstrate the advantages of the novel BRDF model by showing its use for
      reflection component separation and for exploring the space of isotropic BRDFs.

PMID- 21200404
TI  - A functional C-terminal TRAF3-binding site in MAVS participates in positive and
      negative regulation of the IFN antiviral response.
AB  - Recognition of viral RNA structures by the cytosolic sensor retinoic acid
      inducible gene-I (RIG-I) results in the activation of signaling cascades that
      culminate with the generation of the type I interferon (IFN) antiviral response.
      Onset of antiviral and inflammatory responses to viral pathogens necessitates the
      regulated spatiotemporal recruitment of signaling adapters, kinases and
      transcriptional proteins to the mitochondrial antiviral signaling protein (MAVS).
      We previously demonstrated that the serine/threonine kinase IKKepsilon is
      recruited to the C-terminal region of MAVS following Sendai or vesicular
      stomatitis virus (VSV) infection, mediated by Lys63-linked polyubiquitination of
      MAVS at Lys500, resulting in inhibition of downstream IFN signaling (Paz et al,
      Mol Cell Biol, 2009). In this study, we demonstrate that C-terminus of MAVS
      harbors a novel TRAF3-binding site in the aa450-468 region of MAVS. A consensus
      TRAF-interacting motif (TIM), 455-PEENEY-460, within this site is required for
      TRAF3 binding and activation of IFN antiviral response genes, whereas mutation of
      the TIM eliminates TRAF3 binding and the downstream IFN response. Reconstitution
      of MAVS(-/-) mouse embryo fibroblasts with a construct expressing a TIM-mutated
      version of MAVS failed to restore the antiviral response or block VSV
      replication, whereas wild-type MAVS reconstituted antiviral inhibition of VSV
      replication. Furthermore, recruitment of IKKepsilon to an adjacent C-terminal
      site (aa 468-540) in MAVS via Lys500 ubiquitination decreased TRAF3 binding and
      protein stability, thus contributing to IKKepsilon-mediated shutdown of the IFN
      response. This study demonstrates that MAVS harbors a functional C-terminal TRAF3
      binding site that participates in positive and negative regulation of the IFN
      antiviral response.

PMID- 21200407
TI  - Broadband terahertz circular polarizers with single- and double-helical array
      metamaterials.
AB  - A new broadband terahertz circular polarizer with a double-helix structure is
      proposed in this paper. Furthermore, we systematically simulated the performance
      of single- and double-helix circular polarizers. Our numerical simulation results
      show that the function regions of double-helical metamaterials are about 50%
      broader than those of the single-helical metamaterials in terahertz. We also
      analyzed the dependence of the performance of the single- and double-helix
      metamaterials on different structure parameters. Following the antenna theory and
      the metal wire grating theory, proper explanations were given to interpret the
      changes of performance with various structure parameters and the difference
      between the single and double helix.

PMID- 21200408
TI  - Study of scattering from a sphere with an eccentrically located spherical
      inclusion by generalized Lorenz-Mie theory: internal and external field
      distribution.
AB  - Based on the recent results in the generalized Lorenz-Mie theory, solutions for
      scattering problems of a sphere with an eccentrically located spherical inclusion
      illuminated by an arbitrary shaped electromagnetic beam in an arbitrary
      orientation are obtained. Particular attention is paid to the description and
      application of an arbitrary shaped beam in an arbitrary orientation to the
      scattering problem under study. The theoretical formalism is implemented in a
      homemade computer program written in FORTRAN. Numerical results concerning
      spatial distributions of both internal and external fields are displayed in
      different formats in order to properly display exemplifying results. More
      specifically, as an example, we consider the case of a focused fundamental
      Gaussian beam (TEM(00) mode) illuminating a glass sphere (having a real
      refractive index equal to 1.50) with an eccentrically located spherical water
      inclusion (having a real refractive index equal to 1.33). Displayed results are
      for various parameters of the incident electromagnetic beam (incident
      orientation, beam waist radius, location of the beam waist center) and of the
      scatterer system (location of the inclusion inside the host sphere and relative
      diameter of the inclusion to the host sphere).

PMID- 21200409
TI  - Minimization of the shadow patterns produced by periodic mesh grids in extreme
      ultraviolet telescopes.
AB  - Thin metallic films are used as passband filters in space telescopes operating in
      the extreme ultraviolet (EUV). Because of their thinness, typically 100 to 200
      nm, they are very sensitive to static pressure differentials and to mechanic and
      acoustic vibrations. Therefore, they are difficult to manage in all phases of a
      space program, from manufacturing to vacuum testing to launch. A common solution
      to this problem is to reinforce them with fine mesh grids with pitches ranging
      from a few hundred micrometers to a few millimeters. Depending on their location
      in the optical path, the main effect of these periodic grids is either to
      diffract light or to cast penumbral shadows on the focal plane. In this paper, we
      analyze the formation of the shadow modulation patterns and derive design rules
      to minimize their amplitude. The minimization principle is illustrated by an
      application to a solar EUV telescope.

PMID- 21200410
TI  - When is polarimetric imaging preferable to intensity imaging for target
      detection?
AB  - We consider target detection in images perturbed with additive noise. We
      determine the conditions in which polarimetric imaging, which consists of
      analyzing of the polarization of the light scattered by the scene before forming
      the image, yields better performance than classical intensity imaging. These
      results give important information to assess the interest of polarimetric imaging
      in a given application.

PMID- 21200411
TI  - Angle-suppressed scattering and optical forces on submicrometer dielectric
      particles.
AB  - We show that submicrometer silicon spheres, whose polarizabilities are completely
      given by their two first Mie coefficients, are an excellent laboratory to test
      effects of both angle-suppressed and resonant differential scattering cross
      sections. Specifically, outstanding scattering angular distributions, with zero
      forward- or backward-scattered intensity, (i.e., the so-called Kerker
      conditions), previously discussed for hypothetical magnetodielectric particles,
      are now observed for those Si objects in the near infrared. Interesting new
      consequences for the corresponding optical forces are derived from the interplay,
      both in and out of resonance, between the electric- and magnetic-induced dipoles.

PMID- 21200412
TI  - Efficient generation and control of different-order orbital angular momentum
      states for communication links.
AB  - We present an optical scheme to encode and decode 2 bits of information into
      different orbital angular momentum (OAM) states of a paraxial optical beam. Our
      device generates the four light angular momentum states of order +/-2 and +/-4 by
      spin-to-orbital angular momentum conversion in a triangular optical loop
      arrangement. The switching among the four OAM states is obtained by changing the
      polarization state of the circulating beam by two quarter-wave plates, and the 2
      bit information is transferred to the beam OAM exploiting a single q plate. The
      polarization of the exit beam is left free for an additional 1 bit of
      information. The switching among the different OAM states can be as fast as a few
      nanoseconds, if suitable electro-optical cells are used. This may be particularly
      useful in communication systems based on light OAM.

PMID- 21200413
TI  - Recurrent neurotropic chloroma: report of a case and review of the literature.
AB  - We are reporting a case of a young woman with acute myelogenous leukemia status
      postallogeneic transplantation who developed multiply recurrent chloromas
      occurring along peripheral nerves in the absence of bone marrow relapse, all
      treated with radiation therapy. The patient is currently free of disease nearly
      four years after her first posttransplant chloroma. The case presented is unique
      for its isolated peripheral nervous system involvement, rare posttransplant
      occurrence, and indolent course without marrow relapse despite multiple
      extramedullary recurrences.

PMID- 21200414
TI  - Extensive and intimate association of the cytoskeleton with forming silica in
      diatoms: control over patterning on the meso- and micro-scale.
AB  - BACKGROUND: The diatom cell wall, called the frustule, is predominantly made out
      of silica, in many cases with highly ordered nano- and micro-scale features.
      Frustules are built intracellularly inside a special compartment, the silica
      deposition vesicle, or SDV. Molecules such as proteins (silaffins and silacidins)
      and long chain polyamines have been isolated from the silica and shown to be
      involved in the control of the silica polymerization. However, we are still
      unable to explain or reproduce in vitro the complexity of structures formed by
      diatoms. METHODS/PRINCIPAL FINDING: In this study, using fluorescence microscopy,
      scanning electron microscopy, and atomic force microscopy, we were able to
      compare and correlate microtubules and microfilaments with silica structure
      formed in diversely structured diatom species. The high degree of correlation
      between silica structure and actin indicates that actin is a major element in the
      control of the silica morphogenesis at the meso and microscale. Microtubules
      appear to be involved in the spatial positioning on the mesoscale and
      strengthening of the SDV. CONCLUSIONS/SIGNIFICANCE: These results reveal the
      importance of top down control over positioning of and within the SDV during
      diatom wall formation and open a new perspective for the study of the mechanism
      of frustule patterning as well as for the understanding of the control of
      membrane dynamics by the cytoskeleton.

PMID- 21200416
TI  - The unknown risk of vertical transmission in sleeping sickness--a literature
      review.
AB  - BACKGROUND: Children with human African trypanosomiasis (HAT) present with a
      range of generally non-specific symptoms. Late diagnosis is frequent with often
      tragic outcomes. Trypanosomes can infect the foetus by crossing the placenta.
      Unequivocal cases of congenital infection that have been reported include newborn
      babies of infected mothers who were diagnosed with HAT in the first 5 days of
      life and children of infected mothers who had never entered an endemic country
      themselves. METHODS: This review systematically summarizes the literature on the
      vertical transmission of HAT, to our knowledge for the first time. To approach
      the broader aspects of the subject, articles considering the epidemiology of
      childhood HAT and HAT in pregnancy were also included. The HAT guidelines and
      technical reports of the World Health Organisation, Medecins Sans Frontieres,
      Institut de Recherche pour le Developpement, and of one endemic country were
      reviewed. RESULTS: Publications describing congenital HAT are very limited and
      consist only of single case reports and small case series. Generally it is
      assumed to be a rare event, but it has never been systematically investigated. In
      two publications, it is hypothesized that congenital HAT occurs more often than
      suspected. Not all guidelines and not all HAT literature mention this
      transmission route. CONCLUSIONS: The risk of vertical transmission is unknown.
      Awareness of congenital HAT is insufficient, and as a result opportunities for an
      early diagnosis in newborns may be missed. All HAT guidelines and local HAT
      protocols should stress that in endemic areas pregnant women should be
      systematically checked for HAT and that newborns of HAT infected mothers should
      be assessed for the disease as soon as possible. Studies on the impact of HAT on
      fertility and pregnancy and studies on congenital HAT are long overdue.

PMID- 21200415
TI  - Kinetics of rhodopsin deactivation and its role in regulating recovery and
      reproducibility of rod photoresponse.
AB  - The single photon response (SPR) in vertebrate phototransduction is regulated by
      the dynamics of R* during its lifetime, including the random number of
      phosphorylations, the catalytic activity and the random sojourn time at each
      phosphorylation level. Because of this randomness the electrical responses are
      expected to be inherently variable. However the SPR is highly reproducible. The
      mechanisms that confer to the SPR such a low variability are not completely
      understood. The kinetics of rhodopsin deactivation is investigated by a
      Continuous Time Markov Chain (CTMC) based on the biochemistry of rhodopsin
      activation and deactivation, interfaced with a spatio-temporal model of
      phototransduction. The model parameters are extracted from the photoresponse data
      of both wild type and mutant mice, having variable numbers of phosphorylation
      sites and, with the same set of parameters, the model reproduces both WT and
      mutant responses. The sources of variability are dissected into its components,
      by asking whether a random number of turnoff steps, a random sojourn time between
      steps, or both, give rise to the known variability. The model shows that only the
      randomness of the sojourn times in each of the phosphorylated states contributes
      to the Coefficient of Variation (CV) of the response, whereas the randomness of
      the number of R* turnoff steps has a negligible effect. These results counter the
      view that the larger the number of decay steps of R*, the more stable the
      photoresponse is. Our results indicate that R* shutoff is responsible for the
      variability of the photoresponse, while the diffusion of the second messengers
      acts as a variability suppressor.

PMID- 21200417
TI  - Revisiting the immune trypanolysis test to optimise epidemiological surveillance
      and control of sleeping sickness in West Africa.
AB  - BACKGROUND: Because of its high sensitivity and its ease of use in the field, the
      card agglutination test for trypanosomiasis (CATT) is widely used for mass
      screening of sleeping sickness. However, the CATT exhibits false-positive results
      (i) raising the question of whether CATT-positive subjects who are negative in
      parasitology are truly exposed to infection and (ii) making it difficult to
      evaluate whether Trypanosoma brucei (T.b.) gambiense is still circulating in
      areas of low endemicity. The objective of this study was to assess the value of
      the immune trypanolysis test (TL) in characterising the HAT status of CATT
      positive subjects and to monitor HAT elimination in West Africa.
      METHODOLOGY/PRINCIPAL FINDINGS: TL was performed on plasma collected from CATT
      positive persons identified within medical surveys in several West African HAT
      foci in Guinea, Cote d'Ivoire and Burkina Faso with diverse epidemiological
      statuses (active, latent, or historical). All HAT cases were TL+. All subjects
      living in a nonendemic area were TL-. CATT prevalence was not correlated with HAT
      prevalence in the study areas, whereas a significant correlation was found using
      TL. CONCLUSION AND SIGNIFICANCE: TL appears to be a marker for contact with T.b.
      gambiense. TL can be a tool (i) at an individual level to identify
      nonparasitologically confirmed CATT-positive subjects as well as those who had
      contact with T.b. gambiense and should be followed up, (ii) at a population level
      to identify priority areas for intervention, and (iii) in the context of HAT
      elimination to identify areas free of HAT.

PMID- 21200418
TI  - Neurocysticercosis may no longer be a public health problem in Mexico.

PMID- 21200419
TI  - Quantifying the spatial dimension of dengue virus epidemic spread within a
      tropical urban environment.
AB  - BACKGROUND: Dengue infection spread in naive populations occurs in an explosive
      and widespread fashion primarily due to the absence of population herd immunity,
      the population dynamics and dispersal of Ae. aegypti, and the movement of
      individuals within the urban space. Knowledge on the relative contribution of
      such factors to the spatial dimension of dengue virus spread has been limited. In
      the present study we analyzed the spatio-temporal pattern of a large dengue virus
      2 (DENV-2) outbreak that affected the Australian city of Cairns (north
      Queensland) in 2003, quantified the relationship between dengue transmission and
      distance to the epidemic's index case (IC), evaluated the effects of indoor
      residual spraying (IRS) on the odds of dengue infection, and generated
      recommendations for city-wide dengue surveillance and control. METHODS AND
      FINDINGS: We retrospectively analyzed data from 383 DENV-2 confirmed cases and
      1,163 IRS applications performed during the 25-week epidemic period. Spatial
      (local k-function, angular wavelets) and space-time (Knox test) analyses
      quantified the intensity and directionality of clustering of dengue cases,
      whereas a semi-parametric Bayesian space-time regression assessed the impact of
      IRS and spatial autocorrelation in the odds of weekly dengue infection. About 63%
      of the cases clustered up to 800 m around the IC's house. Most cases were
      distributed in the NW-SE axis as a consequence of the spatial arrangement of
      blocks within the city and, possibly, the prevailing winds. Space-time analysis
      showed that DENV-2 infection spread rapidly, generating 18 clusters (comprising
      65% of all cases), and that these clusters varied in extent as a function of
      their distance to the IC's residence. IRS applications had a significant
      protective effect in the further occurrence of dengue cases, but only when they
      reached coverage of 60% or more of the neighboring premises of a house.
      CONCLUSION: By applying sound statistical analysis to a very detailed dataset
      from one of the largest outbreaks that affected the city of Cairns in recent
      times, we not only described the spread of dengue virus with high detail but also
      quantified the spatio-temporal dimension of dengue virus transmission within this
      complex urban environment. In areas susceptible to non-periodic dengue epidemics,
      effective disease prevention and control would depend on the prompt response to
      introduced cases. We foresee that some of the results and recommendations derived
      from our study may also be applicable to other areas currently affected or
      potentially subject to dengue epidemics.

PMID- 21200420
TI  - Miltefosine in the treatment of cutaneous leishmaniasis caused by Leishmania
      braziliensis in Brazil: a randomized and controlled trial.
AB  - BACKGROUND: Cutaneous leishmaniasis (CL) is treated with parenteral drugs for
      decades with decreasing rate cures. Miltefosine is an oral medication with anti
      leishmania activity and may increase the cure rates and improve compliance.
      METHODOLOGY/PRINCIPAL FINDINGS: This study is a randomized, open-label,
      controlled clinical trial aimed to evaluate the efficacy and safety of
      miltefosine versus pentavalent antimony (Sb(v)) in the treatment of patients with
      CL caused by Leishmania braziliensis in Bahia, Brazil. A total of 90 patients
      were enrolled in the trial; 60 were assigned to receive miltefosine and 30 to
      receive Sb(v). Six months after treatment, in the intention-to-treat analyses,
      the definitive cure rate was 53.3% in the Sb(v) group and 75% in the miltefosine
      group (difference of 21.7%, 95% CI 0.08% to 42.7%, p = 0.04). Miltefosine was
      more effective than Sb(v) in the age group of 13-65 years-old compared to 2-12
      years-old group (78.9% versus 45% p = 0.02; 68.2% versus 70% p = 1.0,
      respectively). The incidence of adverse events was similar in the Sb(v) and
      miltefosine groups (76.7% vs. 78.3%). Vomiting (41.7%), nausea (40%), and
      abdominal pain (23.3%) were significantly more frequent in the miltefosine group
      while arthralgias (20.7%), mialgias (20.7%) and fever (23.3%) were significantly
      more frequent in the Sb(v) group. CONCLUSIONS: This study demonstrates that
      miltefosine therapy is more effective than standard Sb(v) and safe for the
      treatment of CL caused by Leishmania braziliensis in Bahia, Brazil. TRIAL
      REGISTRATION: Clinicaltrials.gov Identifier NCT00600548.

PMID- 21200421
TI  - Analyses of an expressed sequence tag library from Taenia solium, Cysticerca.
AB  - BACKGROUND: Neurocysticercosis is a disease caused by the oral ingestion of eggs
      from the human parasitic worm Taenia solium. Although drugs are available they
      are controversial because of the side effects and poor efficiency. An expressed
      sequence tag (EST) library is a method used to describe the gene expression
      profile and sequence of mRNA from a specific organism and stage. Such information
      can be used in order to find new targets for the development of drugs and to get
      a better understanding of the parasite biology. METHODS AND FINDINGS: Here an EST
      library consisting of 5760 sequences from the pig cysticerca stage has been
      constructed. In the library 1650 unique sequences were found and of these, 845
      sequences (52%) were novel to T. solium and not identified within other EST
      libraries. Furthermore, 918 sequences (55%) were of unknown function. Amongst the
      25 most frequently expressed sequences 6 had no relevant similarity to other
      sequences found in the Genbank NR DNA database. A prediction of putative signal
      peptides was also performed and 4 among the 25 were found to be predicted with a
      signal peptide. Proposed vaccine and diagnostic targets T24, Tsol18/HP6 and
      Tso31d could also be identified among the 25 most frequently expressed.
      CONCLUSIONS: An EST library has been produced from pig cysticerca and analyzed.
      More than half of the different ESTs sequenced contained a sequence with no
      suggested function and 845 novel EST sequences have been identified. The library
      increases the knowledge about what genes are expressed and to what level. It can
      also be used to study different areas of research such as drug and diagnostic
      development together with parasite fitness via e.g. immune modulation.

PMID- 21200422
TI  - Granulomatous reactivation during the course of a leprosy infection: reaction or
      relapse.
AB  - BACKGROUND: Leprosy is a chronic granulomatous infectious disease and is still
      endemic in many parts of the world. It causes disabilities which are the
      consequence of nerve damage. This damage is in most cases the result of
      immunological reactions. OBJECTIVES: To investigate the differences between a
      type 1 leprosy (reversal) reaction and relapse on using histopathology. METHODS:
      The histopathological changes in 167 biopsies from 66 leprosy patients were
      studied. The patients were selected when their sequential biopsies demonstrated
      either different patterns or maintained the same pattern of granulomatous
      reaction over more than two years during or after the treatment of leprosy.
      RESULTS: In 57 of the patients studied, a reactivation was seen which coincided
      with a decrease in the bacteriological index (BI), suggesting that this
      reactivation (reversal reaction or type 1 leprosy reaction) coincides with an
      effective capacity for bacteriological clearance. In nine patients, an increase
      of the bacteriologic index (IB) or persistence of solid bacilli occurred during
      the reactivation, indicating proliferative activity, suggestive of a relapse. The
      histopathological aspects of the granulomas were similar in both groups.
      CONCLUSION: Bacterioscopy provided the only means to differentiate a reversal
      reaction from a relapse in patients with granulomatous reactivation. The type 1
      leprosy reaction may be considered as a part effective immune reconstitution
      (reversal, upgrading reaction) or as a mere hypersensitivity reaction
      (downgrading reaction) in a relapse.

PMID- 21200423
TI  - Parasitic worms: knowledge, attitudes, and practices in Western Cote d'Ivoire
      with implications for integrated control.
AB  - BACKGROUND: In the developing world where parasitic worm infections are
      pervasive, preventive chemotherapy is the key strategy for morbidity control.
      However, local knowledge, attitudes, and practices (KAP) of parasitic worms are
      poorly understood, although such information is required for prevention and
      sustainable control. METHODS: We carried out KAP surveys in two rural communities
      of Cote d'Ivoire that were subjected to school-based and community-based research
      and control activities. We used qualitative and quantitative methods. The former
      included observations, in-depth interviews with key informants, and focus group
      discussions with school children and adults. Quantitative methods consisted of a
      structured questionnaire administered to household heads. PRINCIPAL FINDINGS:
      Access to clean water was lacking in both communities and only a quarter of the
      households had functioning latrines. There was a better understanding of soil
      transmitted helminthiasis than intestinal schistosomiasis, but community-based
      rather than school-based interventions appeared to improve knowledge of
      schistosomiasis. In the villages with community-based interventions, three
      quarters of household interviewees knew about intestinal schistosomiasis compared
      to 14% in the village where school-based interventions were implemented
      (P<0.001). Whereas two-thirds of respondents from the community-based
      intervention village indicated that the research and control project was the main
      source of information, only a quarter of the respondents cited the project as the
      main source. CONCLUSIONS/SIGNIFICANCE: Preventive chemotherapy targeting school
      aged children has limitations, as older population segments are neglected, and
      hence lack knowledge about how to prevent and control parasitic worm infections.
      Improved access to clean water and sanitation is necessary, along with health
      education to make a durable impact against helminth infections.

PMID- 21200424
TI  - The extinction of dengue through natural vulnerability of its vectors.
AB  - BACKGROUND: Dengue is the world's most important mosquito-borne viral illness.
      Successful future management of this disease requires an understanding of the
      population dynamics of the vector, especially in the context of changing
      climates. Our capacity to predict future dynamics is reflected in our ability to
      explain the significant historical changes in the distribution and abundance of
      the disease and its vector. METHODOLOGY/PRINCIPAL FINDINGS: Here we combine daily
      weather records with simulation modelling techniques to explain vector (Aedes
      aegypti (L.)) persistence within its current and historic ranges in Australia. We
      show that, in regions where dengue presently occurs in Australia (the Wet Tropics
      region of Far North Queensland), conditions are persistently suitable for year
      round adult Ae. aegypti activity and oviposition. In the historic range, however,
      the vector is vulnerable to periodic extinction due to the combined influence of
      adult activity constraints and stochastic loss of suitable oviposition sites.
      CONCLUSIONS/SIGNIFICANCE: These results, together with changes in water-storage
      behaviour by humans, can explain the observed historical range contraction of the
      disease vector. For these reasons, future eradication of dengue in wet tropical
      regions will be extremely difficult through classical mosquito control methods
      alone. However, control of Ae. aegypti in sub-tropical and temperate regions will
      be greatly facilitated by government policy regulating domestic water-storage.
      Exploitation of the natural vulnerabilities of dengue vectors (e.g., habitat
      specificity, climatic limitations) should be integrated with the emerging novel
      transgenic and symbiotic bacterial control techniques to develop future control
      and elimination strategies.

PMID- 21200425
TI  - Pitfalls in the diagnosis of trypanosomiasis in low endemic countries: a case
      report.

PMID- 21200426
TI  - Fexinidazole--a new oral nitroimidazole drug candidate entering clinical
      development for the treatment of sleeping sickness.
AB  - BACKGROUND: Human African trypanosomiasis (HAT), also known as sleeping sickness,
      is a fatal parasitic disease caused by trypanosomes. Current treatment options
      for HAT are scarce, toxic, no longer effective, or very difficult to administer,
      in particular for the advanced, fatal stage of the disease (stage 2, chronic
      HAT). New safe, effective and easy-to-use treatments are urgently needed. Here it
      is shown that fexinidazole, a 2-substituted 5-nitroimidazole rediscovered by the
      Drugs for Neglected Diseases initiative (DNDi) after extensive compound mining
      efforts of more than 700 new and existing nitroheterocycles, could be a short
      course, safe and effective oral treatment curing both acute and chronic HAT and
      that could be implemented at the primary health care level. To complete the
      preclinical development and meet the regulatory requirements before initiating
      human trials, the anti-parasitic properties and the pharmacokinetic, metabolic
      and toxicological profile of fexinidazole have been assessed. METHODS AND
      FINDINGS: Standard in vitro and in vivo anti-parasitic activity assays were
      conducted to assess drug efficacy in experimental models for HAT. In parallel, a
      full range of preclinical pharmacology and safety studies, as required by
      international regulatory guidelines before initiating human studies, have been
      conducted. Fexinidazole is moderately active in vitro against African
      trypanosomes (IC50 against laboratory strains and recent clinical isolates ranged
      between 0.16 and 0.93 ug/mL) and oral administration of fexinidazole at doses of
      100 mg/kg/day for 4 days or 200 mg/kg/day for 5 days cured mice with acute and
      chronic infection respectively, the latter being a model for the advanced and
      fatal stage of the disease when parasites have disseminated into the brain. In
      laboratory animals, fexinidazole is well absorbed after oral administration and
      readily distributes throughout the body, including the brain. The absolute
      bioavailability of oral fexinidazole was 41% in mice, 30% in rats, and 10% in
      dogs. Furthermore, fexinidazole is rapidly metabolised in vivo to at least two
      biologically active metabolites (a sulfoxide and a sulfone derivative) that
      likely account for a significant portion of the therapeutic effect. Key
      pharmacokinetic parameter after oral absorption in mice for fexinidazole and its
      sulfoxide and sulfone metabolites are a C(max) of 500, 14171 and 13651 ng/mL
      respectively, and an AUC0-24 of 424, 45031 and 96286 h.ng/mL respectively.
      Essentially similar PK profiles were observed in rats and dogs. Toxicology
      studies (including safety pharmacology and 4-weeks repeated-dose toxicokinetics
      in rat and dog) have shown that fexinidazole is well tolerated. The No Observed
      Adverse Event Levels in the 4-weeks repeated dose toxicity studies in rats and
      dogs was 200 mg/kg/day in both species, with no issues of concern identified for
      doses up to 800 mg/kg/day. While fexinidazole, like many nitroheterocycles, is
      mutagenic in the Ames test due to bacterial specific metabolism, it is not
      genotoxic to mammalian cells in vitro or in vivo as assessed in an in vitro
      micronucleus test on human lymphocytes, an in vivo mouse bone marrow micronucleus
      test, and an ex vivo unscheduled DNA synthesis test in rats. CONCLUSIONS: The
      results of the preclinical pharmacological and safety studies indicate that
      fexinidazole is a safe and effective oral drug candidate with no untoward effects
      that would preclude evaluation in man. The drug has entered first-in-human phase
      I studies in September 2009. Fexinidazole is the first new clinical drug
      candidate with the potential for treating advanced-stage sleeping sickness in
      thirty years.

PMID- 21200427
TI  - Subversion of innate defenses by the interplay between DENV and pre-existing
      enhancing antibodies: TLRs signaling collapse.
AB  - BACKGROUND: The phenomenon of antibody dependent enhancement as a major
      determinant that exacerbates disease severity in DENV infections is well
      accepted. While the detailed mechanism of antibody enhanced disease severity is
      unclear, evidence suggests that it is associated with both increased DENV
      infectivity and suppression of the type I IFN and pro-inflammatory cytokine
      responses. Therefore, it is imperative for us to understand the intracellular
      mechanisms altered during ADE infection to decipher the mechanism of severe
      pathogenesis. METHODOLOGY/PRINCIPAL FINDINGS: In this present work, qRT-PCR,
      immunoblotting and gene array analysis were conducted to determine whether DENV
      antibody complex infection exerts a suppressive effect on the expression and/or
      function of the pathogen recognition patterns, focusing on the TLR-signaling
      pathway. We show here that FcgammaRI and FcgammaRIIa synergistically facilitated
      entry of DENV-antibody complexes into monocytic THP-1 cells. Ligation between
      DENV-antibody complexes and FcR not only down regulated TLRs gene expression but
      also up regulated SARM, TANK, and negative regulators of the NF-kappaB pathway,
      resulting in suppression of innate responses but increased viral production.
      These results were confirmed by blocking with anti-FcgammaRI or anti-FcgammaRIIa
      antibodies which reduced viral production, up-regulated IFN-beta synthesis, and
      increased gene expression in the TLR-dependent signaling pathway. The negative
      impact of DENV-ADE infection on the TLR-dependent pathway was strongly supported
      by gene array screening which revealed that both MyD88-dependent and -independent
      signaling molecules were down regulated during DENV-ADE infection. Importantly,
      the same phenomenon was seen in PBMC of secondary DHF/DSS patients but not in
      PBMC of DF patients. CONCLUSIONS/SIGNIFICANCE: Our present work demonstrates the
      mechanism by which DENV uses pre-existing immune mediators to defeat the
      principal activating pathway of innate defense resulting in suppression of an
      array of innate immune responses. Interestingly, this phenomenon specifically
      occurred during the severe form of DENV infection but not in the mild form of
      disease.

PMID- 21200428
TI  - A case and review of noma.

PMID- 21200429
TI  - Bayesian geostatistical analysis and prediction of Rhodesian human African
      trypanosomiasis.
AB  - BACKGROUND: The persistent spread of Rhodesian human African trypanosomiasis
      (HAT) in Uganda in recent years has increased concerns of a potential overlap
      with the Gambian form of the disease. Recent research has aimed to increase the
      evidence base for targeting control measures by focusing on the environmental and
      climatic factors that control the spatial distribution of the disease.
      OBJECTIVES: One recent study used simple logistic regression methods to explore
      the relationship between prevalence of Rhodesian HAT and several social,
      environmental and climatic variables in two of the most recently affected
      districts of Uganda, and suggested the disease had spread into the study area due
      to the movement of infected, untreated livestock. Here we extend this study to
      account for spatial autocorrelation, incorporate uncertainty in input data and
      model parameters and undertake predictive mapping for risk of high HAT prevalence
      in future. MATERIALS AND METHODS: Using a spatial analysis in which a generalised
      linear geostatistical model is used in a Bayesian framework to account explicitly
      for spatial autocorrelation and incorporate uncertainty in input data and model
      parameters we are able to demonstrate a more rigorous analytical approach,
      potentially resulting in more accurate parameter and significance estimates and
      increased predictive accuracy, thereby allowing an assessment of the validity of
      the livestock movement hypothesis given more robust parameter estimation and
      appropriate assessment of covariate effects. RESULTS: Analysis strongly supports
      the theory that Rhodesian HAT was imported to the study area via the movement of
      untreated, infected livestock from endemic areas. The confounding effect of
      health care accessibility on the spatial distribution of Rhodesian HAT and the
      linkages between the disease's distribution and minimum land surface temperature
      have also been confirmed via the application of these methods. CONCLUSIONS:
      Predictive mapping indicates an increased risk of high HAT prevalence in the
      future in areas surrounding livestock markets, demonstrating the importance of
      livestock trading for continuing disease spread. Adherence to government policy
      to treat livestock at the point of sale is essential to prevent the spread of
      sleeping sickness in Uganda.

PMID- 21200431
TI  - Improving cancer classification accuracy using gene pairs.
AB  - Recent studies suggest that the deregulation of pathways, rather than individual
      genes, may be critical in triggering carcinogenesis. The pathway deregulation is
      often caused by the simultaneous deregulation of more than one gene in the
      pathway. This suggests that robust gene pair combinations may exploit the
      underlying bio-molecular reactions that are relevant to the pathway deregulation
      and thus they could provide better biomarkers for cancer, as compared to
      individual genes. In order to validate this hypothesis, in this paper, we used
      gene pair combinations, called doublets, as input to the cancer classification
      algorithms, instead of the original expression values, and we showed that the
      classification accuracy was consistently improved across different datasets and
      classification algorithms. We validated the proposed approach using nine cancer
      datasets and five classification algorithms including Prediction Analysis for
      Microarrays (PAM), C4.5 Decision Trees (DT), Naive Bayesian (NB), Support Vector
      Machine (SVM), and k-Nearest Neighbor (k-NN).

PMID- 21200430
TI  - Growth factor PDGF-BB stimulates cultured cardiomyocytes to synthesize the
      extracellular matrix component hyaluronan.
AB  - BACKGROUND: Hyaluronan (HA) is a glycosaminoglycan located in the interstitial
      space which is essential for both structural and cell regulatory functions in
      connective tissue. We have previously shown that HA synthesis is up-regulated in
      a rat model of experimental cardiac hypertrophy and that cardiac tissue utilizes
      two different HA synthases in the hypertrophic process. Cardiomyocytes and
      fibroblasts are two major cell types in heart tissue. The fibroblasts are known
      to produce HA, but it has been unclear if cardiomyocytes share the same feature,
      and whether or not the different HA synthases are activated in the different cell
      types. METHODOLOGY/PRINCIPAL FINDINGS: This study shows, for the first time that
      cardiomyocytes can produce HA. Cardiomyocytes (HL-1) and fibroblasts (NIH 3T3)
      were cultivated in absence or presence of the growth factors FGF2, PDGF-BB and
      TGFB2. HA concentration was quantified by ELISA, and the size of HA was estimated
      using dynamic light scattering. Cardiomyocytes synthesized HA but only when
      stimulated by PDGF-BB, whereas fibroblasts synthesized HA without addition of
      growth factors as well as when stimulated by any of the three growth factors.
      When fibroblasts were stimulated by the growth factors, reverse dose dependence
      was observed, where the highest dose induced the least amount of HA. With the
      exception of TGFB2, a trend of reverse dose dependence of HA size was also
      observed. CONCLUSIONS/SIGNIFICANCE: Co-cultivation of cardiomyocytes and
      fibroblasts (80%/20%) increased HA concentration far more that can be explained
      by HA synthesis by the two cell types separately, revealing a crosstalk between
      cardiomyocytes and fibroblasts that induces HA synthesis. We conclude that
      dynamic changes of the myocardium, such as in cardiac hypertrophy, do not depend
      on the cardiomyocyte alone, but are achieved when both cardiomyocytes and
      fibroblasts are present.

PMID- 21200433
TI  - Competitive interactions between invasive Nile tilapia and native fish: the
      potential for altered trophic exchange and modification of food webs.
AB  - Recent studies have highlighted both the positive and negative impacts of species
      invasions. Most of these studies have been conducted on either immobile invasive
      plants or sessile fauna found at the base of food webs. Fewer studies have
      examined the impacts of vagile invasive consumers on native competitors. This is
      an issue of some importance given the controlling influence that consumers have
      on lower order plants and animals. Here, we present results of laboratory
      experiments designed to assess the impacts of unintended aquaculture releases of
      the Nile tilapia (Oreochromis niloticus), in estuaries of the Gulf of Mexico, on
      the functionally similar redspotted sunfish (Lepomis miniatus). Laboratory choice
      tests showed that tilapia prefer the same structured habitat that native sunfish
      prefer. In subsequent interspecific competition experiments, agonistic tilapia
      displaced sunfish from their preferred structured habitats. When a piscivore
      (largemouth bass) was present in the tank with both species, the survival of
      sunfish decreased. Based on these findings, if left unchecked, we predict that
      the proliferation of tilapia (and perhaps other aggressive aquaculture fishes)
      will have important detrimental effects on the structure of native food webs in
      shallow, structured coastal habitats. While it is likely that the impacts of
      higher trophic level invasive competitors will vary among species, these results
      show that consequences of unintended releases of invasive higher order consumers
      can be important.

PMID- 21200432
TI  - DETC induces Leishmania parasite killing in human in vitro and murine in vivo
      models: a promising therapeutic alternative in Leishmaniasis.
AB  - BACKGROUND: Chemotherapy remains the primary tool for treatment and control of
      human leishmaniasis. However, currently available drugs present serious problems
      regarding side-effects, variable efficacy, and cost. Affordable and less toxic
      drugs are urgently needed for leishmaniasis. METHODOLOGY/PRINCIPAL FINDINGS: We
      demonstrate, by microscopy and viability assays, that superoxide dismutase
      inhibitor diethyldithiocarbamate (DETC) dose-dependently induces parasite killing
      (p<0.001) and is able to "sterilize" Leishmania amazonensis infection at 2 mM in
      human macrophages in vitro. We also show that DETC-induced superoxide production
      (p<0.001) and parasite destruction (p<0.05) were reverted by the addition of the
      antioxidant N-acetylcysteine, indicating that DETC-induced killing occurs through
      oxidative damage. Furthermore, ultrastructural analysis by electron microscopy
      demonstrates a rapid and highly selective destruction of amastigotes in the
      phagosome upon DETC treatment, without any apparent damage to the host cell,
      including its mitochondria. In addition, DETC significantly induced parasite
      killing in Leishmania promastigotes in axenic culture. In murine macrophages
      infected with Leishmania braziliensis, DETC significantly induced in vitro
      superoxide production (p = 0.0049) and parasite killing (p = 0.0043). In vivo
      treatment with DETC in BALB/C mice infected with Leishmania braziliensis caused a
      significant decrease in lesion size (p<0.0001), paralleled by a 100-fold decrease
      (p = 0.0087) in parasite burden. CONCLUSIONS/SIGNIFICANCE: Due to its strong
      leishmanicidal effect in human macrophages in vitro, its in vivo effectiveness in
      a murine model, and its previously demonstrated in vivo safety profile in HIV
      treatment, DETC treatment might be considered as a valuable therapeutic option in
      human leishmaniasis, including HIV/Leishmania co-infection.

PMID- 21200434
TI  - High accuracy decoding of movement target direction in non-human primates based
      on common spatial patterns of local field potentials.
AB  - BACKGROUND: The current development of brain-machine interface technology is
      limited, among other factors, by concerns about the long-term stability of single
      and multi-unit neural signals. In addition, the understanding of the relation
      between potentially more stable neural signals, such as local field potentials,
      and motor behavior is still in its early stages. METHODOLOGY/PRINCIPAL FINDINGS:
      We tested the hypothesis that spatial correlation patterns of neural data can be
      used to decode movement target direction. In particular, we examined local field
      potentials (LFP), which are thought to be more stable over time than single unit
      activity (SUA). Using LFP recordings from chronically implanted electrodes in the
      dorsal premotor and primary motor cortex of non-human primates trained to make
      arm movements in different directions, we made the following observations: (i) it
      is possible to decode movement target direction with high fidelity from the
      spatial correlation patterns of neural activity in both primary motor (M1) and
      dorsal premotor cortex (PMd); (ii) the decoding accuracy of LFP was similar to
      the decoding accuracy obtained with the set of SUA recorded simultaneously; (iii)
      directional information varied with the LFP frequency sub-band, being greater in
      low (0.3-4 Hz) and high (48-200 Hz) frequency bands than in intermediate bands;
      (iv) the amount of directional information was similar in M1 and PMd; (v)
      reliable decoding was achieved well in advance of movement onset; and (vi) LFP
      were relatively stable over a period of one week. CONCLUSIONS/SIGNIFICANCE: The
      results demonstrate that the spatial correlation patterns of LFP signals can be
      used to decode movement target direction. This finding suggests that parameters
      of movement, such as target direction, have a stable spatial distribution within
      primary motor and dorsal premotor cortex, which may be used for brain-machine
      interfaces.

PMID- 21200435
TI  - Stem cell factor expression after renal ischemia promotes tubular epithelial
      survival.
AB  - BACKGROUND: Renal ischemia leads to apoptosis of tubular epithelial cells and
      results in decreased renal function. Tissue repair involves re-epithelialization
      of the tubular basement membrane. Survival of the tubular epithelium following
      ischemia is therefore important in the successful regeneration of renal tissue.
      The cytokine stem cell factor (SCF) has been shown to protect the tubular
      epithelium against apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: In a mouse model
      for renal ischemia/reperfusion injury, we studied how expression of c-KIT on
      tubular epithelium and its ligand SCF protect cells against apoptosis.
      Administration of SCF specific antisense oligonucleotides significantly decreased
      specific staining of SCF following ischemia. Reduced SCF expression resulted in
      impaired renal function, increased tubular damage and increased tubular
      epithelial apoptosis, independent of inflammation. In an in vitro hypoxia model,
      stimulation of tubular epithelial cells with SCF activated survival signaling and
      decreased apoptosis. CONCLUSIONS/SIGNIFICANCE: Our data indicate an important
      role for c-KIT and SCF in mediating tubular epithelial cell survival via an
      autocrine pathway.

PMID- 21200437
TI  - In a subgroup of high-risk Asians, telmisartan was non-inferior to ramipril and
      better tolerated in the prevention of cardiovascular events.
AB  - BACKGROUND AND OBJECTIVES: Results of the recently published ONTARGET study (The
      Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial)
      showed that telmisartan (80 mg/day) was non-inferior to ramipril (10 mg/day) in
      reducing cardiovascular events. Clinicians in Asia doubt tolerability of these
      doses for their patients. We therefore analyzed data from this study and a
      parallel study TRANSCEND (Telmisartan Randomized Assessment Study in ACE
      Intolerant Subjects with Cardiovascular Disease). Our objectives were to compare
      Asians and non-Asians with respect to the following: 1) Effectiveness of
      telmisartan vs. ramipril in reducing cardiovascular events;2) Proportions who
      reached the full dose of telmisartan, ramipril or placebo; and3) Proportions of
      overall discontinuations, and discontinuations due to adverse effects. METHOD:
      The ONTARGET study randomized 25,620 patients at risk of cardiovascular events to
      ramipril, telmisartan, or their combination. The primary composite endpoint was
      death caused by cardiovascular disease, acute MI, stroke, and hospitalization
      because of congestive heart failure. TRANSCEND randomized 5926 high-risk patients
      with a history of intolerance to ACE-inhibitors to telmisartan or placebo. The
      primary outcome was the same. In this substudy, we compared Asians and non-Asians
      as to how well they tolerated telmisartan (given in both studies) and ramipril
      (given in ONTARGET). RESULTS: 1) Telmisartan was non-inferior to ramipril in
      lowering the primary endpoint among Asians (RR = 0.92; 95% CI: 0.74, 1.13); 2)
      more Asians achieved the full dose of either drug; 3) less withdrew (overall);
      and 4) less withdrew for adverse effects. Furthermore, telmisartan was better
      tolerated than ramipril. This advantage was greater among Asians. CONCLUSION AND
      SIGNIFICANCE: Although Asians had lower BMI than non-Asians, Asians tolerated
      both drugs better. Regulatory agencies require reporting of safety and
      effectiveness data by ethnicity, but few comply with this requirement. This study
      shows that safety data in ethnic subgroups can help assess applicability of
      results to specific populations. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00153101.

PMID- 21200438
TI  - Functional neurokinin and NMDA receptor activity in an animal naturally lacking
      substance P: the naked mole-rat.
AB  - Naked mole-rats are extremely unusual among mammals in that their cutaneous C
      fibers lack the neuropeptide Substance P (SP). In other mammals, SP plays an
      important role in nociception: it is released from C-fibers onto spinal neurons
      where it facilitates NMDA receptor activity and causes sensitization that can
      last for minutes, hours or days. In the present study, we tested the effects of
      intrathecal application of: 1) SP, 2) an SP antagonist (GR-82334), and 3) an NMDA
      antagonist (APV) on heat-evoked foot withdrawal. In the naked mole-rat, at a high
      enough concentration, application of SP caused a large, immediate, and long
      lasting sensitization of foot withdrawal latency that was transiently reversed by
      application of either antagonist. However, neither SP nor NMDA antagonists had an
      effect when administered alone to naive animals. In contrast, both antagonists
      induced an increase in basal withdrawal latency in mice. These results indicate
      that spinal neurons in naked mole-rats have functional SP and NMDA receptors, but
      that these receptors do not participate in heat-evoked foot withdrawal unless SP
      is experimentally introduced. We propose that the natural lack of SP in naked
      mole-rat C-fibers may have resulted during adaptation to living in a chronically
      high carbon dioxide, high ammonia environment that, in other mammals, would
      stimulate C-fibers and evoke nocifensive behavior.

PMID- 21200436
TI  - Sex- and diet-specific changes of imprinted gene expression and DNA methylation
      in mouse placenta under a high-fat diet.
AB  - BACKGROUND: Changes in imprinted gene dosage in the placenta may compromise the
      prenatal control of nutritional resources. Indeed monoallelic behaviour and
      sensitivity to changes in regional epigenetic state render imprinted genes both
      vulnerable and adaptable. METHODS AND FINDINGS: We investigated whether a high
      fat diet (HFD) during pregnancy modified the expression of imprinted genes and
      local and global DNA methylation patterns in the placenta. Pregnant mice were fed
      a HFD or a control diet (CD) during the first 15 days of gestation. We compared
      gene expression patterns in total placenta homogenates, for male and female
      offspring, by the RT-qPCR analysis of 20 imprinted genes. Sexual dimorphism and
      sensitivity to diet were observed for nine genes from four clusters on
      chromosomes 6, 7, 12 and 17. As assessed by in situ hybridization, these changes
      were not due to variation in the proportions of the placental layers. Bisulphite
      sequencing analysis of 30 CpGs within the differentially methylated region (DMR)
      of the chromosome 17 cluster revealed sex- and diet-specific differential
      methylation of individual CpGs in two conspicuous subregions. Bioinformatic
      analysis suggested that these differentially methylated CpGs might lie within
      recognition elements or binding sites for transcription factors or factors
      involved in chromatin remodelling. Placental global DNA methylation, as assessed
      by the LUMA technique, was also sexually dimorphic on the CD, with lower
      methylation levels in male than in female placentae. The HFD led to global DNA
      hypomethylation only in female placenta. Bisulphite pyrosequencing showed that
      neither B1 nor LINE repetitive elements could account for these differences in
      DNA methylation. CONCLUSIONS: A HFD during gestation triggers sex-specific
      epigenetic alterations within CpG and throughout the genome, together with the
      deregulation of clusters of imprinted genes important in the control of many
      cellular, metabolic and physiological functions potentially involved in
      adaptation and/or evolution. These findings highlight the importance of studying
      both sexes in epidemiological protocols and dietary interventions.

PMID- 21200439
TI  - mTORC1-S6K activation by endotoxin contributes to cytokine up-regulation and
      early lethality in animals.
AB  - BACKGROUND: mTORC1 (mammalian target of rapamycin complex 1) activation has been
      demonstrated in response to endotoxin challenge, but the mechanism and
      significance are unclear. We investigated the effect of mTORC1 suppression in an
      animal model of endotoxemia and in a cellular model of endotoxin signaling.
      METHODOLOGY/PRINCIPAL FINDINGS: Mice were treated with the mTORC1 inhibitor
      rapamycin or vehicle prior to lethal endotoxin challenge. Mortality and cytokine
      levels were assessed. Cultured macrophage-like cells were challenged with
      endotoxin with or without inhibitors of various pathways known to be upstream of
      mTORC1. Activated pathways, including downstream S6K pathway, were assessed by
      immunoblots. We found that mTORC1-S6K suppression by rapamycin delayed mortality
      of mice challenged with lethal endotoxin, and was associated with dampened
      circulating levels of VEGF, IL-1beta, IFN-gamma and IL-5. Furthermore, in vitro
      cellular studies demonstrated that LPS (lipopolysaccharide) activation of mTORC1
      S6K still occurs in the presence of PI3K-Akt inhibition alone, but can be
      suppressed by concurrent inhibition of PI3K-Akt and MEK-ERK pathways.
      CONCLUSIONS/SIGNIFICANCE: We conclude that cellular activation of mTORC1-S6K
      contributes to cytokine up-regulation and mortality in response to endotoxin, and
      may occur via multiple pathways.

PMID- 21200440
TI  - Complexity of the tensegrity structure for dynamic energy and force distribution
      of cytoskeleton during cell spreading.
AB  - Cytoskeleton plays important roles in intracellular force equilibrium and
      extracellular force transmission from/to attaching substrate through focal
      adhesions (FAs). Numerical simulations of intracellular force distribution to
      describe dynamic cell behaviors are still limited. The tensegrity structure
      comprises tension-supporting cables and compression-supporting struts that
      represent the actin filament and microtubule respectively, and has many features
      consistent with living cells. To simulate the dynamics of intracellular force
      distribution and total stored energy during cell spreading, the present study
      employed different complexities of the tensegrity structures by using octahedron
      tensegrity (OT) and cuboctahedron tensegrity (COT). The spreading was simulated
      by assigning specific connection nodes for radial displacement and attachment to
      substrate to form FAs. The traction force on each FA was estimated by summarizing
      the force carried in sounding cytoskeletal elements. The OT structure consisted
      of 24 cables and 6 struts and had limitations soon after the beginning of
      spreading by declining energy stored in struts indicating the abolishment of
      compression in microtubules. The COT structure, double the amount of cables and
      struts than the OT structure, provided sufficient spreading area and expressed
      similar features with documented cell behaviors. The traction force pointed
      inward on peripheral FAs in the spread out COT structure. The complex structure
      in COT provided further investigation of various FA number during different
      spreading stages. Before the middle phase of spreading (half of maximum spreading
      area), cell attachment with 8 FAs obtained minimized cytoskeletal energy. The
      maximum number of 12 FAs in the COT structure was required to achieve further
      spreading. The stored energy in actin filaments increased as cells spread out,
      while the energy stored in microtubules increased at initial spreading, peaked in
      middle phase, and then declined as cells reached maximum spreading. The dynamic
      flows of energy in struts imply that microtubules contribute to structure
      stabilization.

PMID- 21200442
TI  - High frequency asynchronous magnetic bead rotation for improved biosensors.
AB  - Biosensors with increasingly high sensitivity are crucial for probing small scale
      properties. The asynchronous magnetic bead rotation (AMBR) sensor is an emerging
      sensor platform, based on magnetically actuated rotation. Here the frequency
      dependence of the AMBR sensor's sensitivity is investigated. An asynchronous
      rotation frequency of 145 Hz is achieved. This increased frequency will allow for
      a calculated detection limit of as little as a 59 nm change in bead diameter,
      which is a dramatic improvement over previous AMBR sensors and further enables
      physical and biomedical applications.

PMID- 21200441
TI  - Aggression in low functioning children and adolescents with autistic disorder.
AB  - BACKGROUND: Parents, caregivers and mental health professionals have often
      reported violence and aggression in children or adolescents with autistic
      disorder. However, most of these observations derived from anecdotal reports, and
      studies on frequency and characterization of aggression in autism remain limited.
      Our objective was to better characterize and understand the different types of
      aggressive behaviors displayed by a large group of individuals with autism in
      different observational situations. METHODOLOGY/FINDINGS: The study was conducted
      on 74 children and adolescents with autism and 115 typically developing control
      individuals matched for sex, age and pubertal stage. Other-Injurious Behaviors
      (OIB) were assessed in three observational situations (parents at home, two
      caregivers at day-care, a nurse and a child psychiatrist during blood drawing)
      using validated scales. The frequency of OIB was significantly higher in
      individuals with autism compared to typically developing control individuals
      during the blood drawing (23% vs. 0%, P<0 .01). The parents observed
      significantly less OIB in their children than caregivers (34% vs. 58%, P<0.05).
      In addition, the most frequent concurrent behaviors occurring just before the
      appearance of OIB in individuals with autism were anxiety-related behaviors and
      excitation according to the parental as well as the caregiver observation.
      CONCLUSIONS/SIGNIFICANCE: The results suggest that in a stressful situation, such
      as the blood drawing, individuals with autism release their stress through
      behaviors such as OIB, whereas typically developing individuals regulate and
      express their stress through cognitive skills such as mental coping strategies,
      symbolization skills with representation and anticipation of the stressful
      situation, social interaction and verbal or non-verbal communication. The
      findings underline also the key role of the environment in assessing OIB and
      developing therapeutic perspectives, with an individual who modulates his/her
      behavior according to the environment, and an environment that perceives this
      behavior and reacts to it with different tolerance thresholds according to the
      observers.

PMID- 21200443
TI  - Study of single particle charge and Brownian motions with surface plasmon
      resonance.
AB  - We demonstrated a method to accurately measure the zeta potentials and surface
      charges of individual particles by surface plasmon resonance microscopy (SPRM).
      The principle is based on the sensitive dependence of surface plasmons in a metal
      surface on the distance between a particle and the surface. By applying a
      periodic (ac) electric field to the metal surface, the charged particle
      oscillates, which is measured with SPRM, from which the zeta potential and the
      surface charge of the particle can be determined. The ac method reduces the
      electro-osmotic effect and noises induced by Brownian motions and allows for the
      rapid determination of the zeta potentials of individual particles.

PMID- 21200444
TI  - Vibration energy harvesting using piezoelectric unimorph cantilevers with unequal
      piezoelectric and nonpiezoelectric lengths.
AB  - We have examined a piezoelectric unimorph cantilever (PUC) with unequal
      piezoelectric and nonpiezoelectric lengths for vibration energy harvesting
      theoretically by extending the analysis of a PUC with equal piezoelectric and
      nonpiezoelectric lengths. The theoretical approach was validated by experiments.
      A case study showed that for a fixed vibration frequency, the maximum open
      circuit induced voltage which was important for charge storage for later use
      occurred with a PUC that had a nonpiezoelectric-to-piezoelectric length ratio
      greater than unity, whereas the maximum power when the PUC was connected to a
      resistor for immediate power consumption occurred at a unity nonpiezoelectric-to
      piezoelectric length ratio.

PMID- 21200445
TI  - Carbon nanotube composite optoacoustic transmitters for strong and high frequency
      ultrasound generation.
AB  - We demonstrate carbon nanotube (CNT) composite-based optoacoustic transmitters
      that generate strong and high frequency ultrasound. The composite consists of
      CNTs grown on a substrate, which are embedded in elastomeric polymer used as an
      acoustic transfer medium. Under pulsed laser excitation, the composite generates
      very strong optoacoustic pressure: 18 times stronger than a Cr film reference and
      five times stronger than a gold nanoparticle composite with the same polymer.
      This enhancement persists over a broadband frequency range of up to 120 MHz and
      is confirmed by calculation. We suggest the CNT-polymer composites as highly
      efficient optoacoustic transmitters for high resolution ultrasound imaging.

PMID- 21200446
TI  - Energy dissipation in microfluidic beam resonators: Dependence on mode number.
AB  - Energy dissipation experienced by vibrating microcantilever beams immersed in
      fluid is strongly dependent on the mode of vibration, with quality factors
      typically increasing with mode number. Recently, we examined energy dissipation
      in a new class of cantilever device that embeds a microfluidic channel in its
      interior-the fundamental mode of vibration only was considered. Due to its
      importance in practice, we examine the effect of mode number on energy
      dissipation in these microfluidic beam resonators. Interestingly, and in contrast
      to other cantilever devices, we find that the quality factor typically decreases
      with increasing mode number. We explore the underlying physical mechanisms
      leading to this counterintuitive behavior, and provide a detailed comparison to
      experimental measurements for which good agreement is found.

PMID- 21200447
TI  - Erratum: 2-[(E)-(Dimethylamino)methylene-amino]-N-phenylbenzenesulfonamide.
      Corrigendum.
AB  - Corrections are made to the name of the author and the address in Zhong [Acta
      Cryst. (2007), E63, o4446].[This corrects the article DOI:
      10.1107/S1600536807050040.].